PMID- 22453055
TI  - Annotation of primate miRNAs by high throughput sequencing of small RNA
      libraries.
AB  - BACKGROUND: In addition to genome sequencing, accurate functional annotation of
      genomes is required in order to carry out comparative and evolutionary analyses
      between species. Among primates, the human genome is the most extensively
      annotated. Human miRNA gene annotation is based on multiple lines of evidence
      including evidence for expression as well as prediction of the characteristic
      hairpin structure. In contrast, most miRNA genes in non-human primates are
      annotated based on homology without any expression evidence. We have sequenced
      small-RNA libraries from chimpanzee, gorilla, orangutan and rhesus macaque from
      multiple individuals and tissues. Using patterns of miRNA expression in
      conjunction with a model of miRNA biogenesis we used these high-throughput
      sequencing data to identify novel miRNAs in non-human primates. RESULTS: We
      predicted 47 new miRNAs in chimpanzee, 240 in gorilla, 55 in orangutan and 47 in
      rhesus macaque. The algorithm we used was able to predict 64% of the previously
      known miRNAs in chimpanzee, 94% in gorilla, 61% in orangutan and 71% in rhesus
      macaque. We therefore added evidence for expression in between one and five
      tissues to miRNAs that were previously annotated based only on homology to human
      miRNAs. We increased from 60 to 175 the number miRNAs that are located in
      orthologous regions in humans and the four non-human primate species studied
      here. CONCLUSIONS: In this study we provide expression evidence for homology
      based annotated miRNAs and predict de novo miRNAs in four non-human primate
      species. We increased the number of annotated miRNA genes and provided evidence
      for their expression in four non-human primates. Similar approaches using
      different individuals and tissues would improve annotation in non-human primates
      and allow for further comparative studies in the future.

PMID- 22453056
TI  - Treatment for a complicated crown-root fracture with intentional replantation: a
      case report with a 3.5-year follow up.
AB  - Crown-root fractures are always challenging for pediatric dentists because of
      their complicated treatments and uncertain prognosis. The purpose of this case
      report was to describe a severe crown-root fracture successfully treated by
      multidisciplinary approaches including intentional replantation. After a 3.5-year
      follow up, the patient felt comfortable and satisfied with her tooth, and the
      prosthesis was functionally and esthetically acceptable. It is recommended that
      multidisciplinary treatment with intentional replantation is effective and
      necessary for similar cases to be conservatively managed.

PMID- 22453057
TI  - Haemolytic anaemia in an HIV-infected patient with severe falciparum malaria
      after treatment with oral artemether-lumefantrine.
AB  - Intravenous (i.v.) artesunate is now the recommended first-line treatment of
      severe falciparum malaria in adults and children by WHO guidelines. Nevertheless,
      several cases of haemolytic anaemia due to i.v. artesunate treatment have been
      reported. This paper describes the case of an HIV-infected patient with severe
      falciparum malaria who was diagnosed with haemolytic anaemia after treatment with
      oral artemether-lumefantrine.The patient presented with fever, headache, and
      arthromyalgia after returning from Central African Republic where he had been
      working. The blood examination revealed acute renal failure, thrombocytopaenia
      and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and
      Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria
      according to the laboratory WHO criteria was diagnosed. A treatment with quinine
      and doxycycline for the first 12 hours was initially administered, followed by
      arthemeter/lumefantrine (Riamet((r))) for a further three days. At day 10, a
      diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l).
      Hereditary and autoimmune disorders and other infections were excluded through
      bone marrow aspiration, total body TC scan and a wide panel of molecular and
      serologic assays. The patient was treated by transfusion of six units of packed
      blood red cell. He was discharged after complete remission at day 25. At present,
      the patient is in a good clinical condition and there is no evidence of
      haemolytic anaemia recurrence.This is the first report of haemolytic anaemia
      probably associated with oral artemether/lumefantrine. Further research is
      warranted to better define the adverse events occurring during combination
      therapy with artemisinin derivatives.

PMID- 22453058
TI  - Lysyl oxidase: from basic science to future cancer treatment.
AB  - In this mini-review, we discuss the physiological and pathological roles of lysyl
      oxidase (LOX) and its family, LOX-like proteins (LOXL), in relation to prognosis
      of major cancers. The number of reports on LOX family is numerous. We have
      decided to review the articles that were recently published (i.e. past 5 years).
      Experimental techniques in molecular biology have advanced surprisingly in the
      past decade. Accordingly, the results of the studies are more reliable. Most
      studies reached the same conclusion; a higher LOX- or LOXL- expression is
      associated with a poor prognosis. Molecular experiments have already started
      aiming for clinical application, and the results are encouraging. Suppressing LOX
      or LOXL activities resulted in lower cell motility in collagen gel and, moreover,
      succeeded in reducing metastases in mice. LOX family members were originally
      recognized as molecules that cross-link collagen fibers in the extracellular
      matrix. Recent studies demonstrated that they are also involved in a phenomenon
      called Epithelial Mesenchymal Transition (EMT). This may affect cell movement and
      cancer cell invasiveness. LOX and LOXL2 are regulated by hypoxia, a major factor
      in the failure of cancer treatment. Here we discuss the molecular biology of the
      LOX family in relation to its role in tumor biology.

PMID- 22453059
TI  - Effects of vitamin D on cardiovascular disease risk factors in polycystic ovary
      syndrome women with vitamin D deficiency.
AB  - BACKGROUND: Vitamin D deficiency is prevalent among women, including patients
      with polycystic ovary syndrome (PCOS). Some studies have suggested that vitamin D
      may have a role in cardiovascular disease (CVD). There is very limited data on
      the vitamin D effect on CVD risk factors in women with PCOS and vitamin D
      deficiency. AIM: To investigate the effect of cholecalciferol on CVD risk factors
      in PCOS women with vitamin D deficiency. METHODS: The study was a randomized,
      placebo-controlled, double blinded trial. Fifty PCOS women with vitamin D
      deficiency (vitamin D, no. = 24; placebo, no. = 26) aged 20-40 yr, were randomly
      assigned to receive 3 oral capsules of 50,000 IU vitamin D3 or a placebo (one
      capsule every 20 days) for two months. Serum vitamin D, PTH, lipid profile,
      apolipoprotein AI (APO-AI), and high sensitive C- reactive protein (hs-CRP) were
      measured at baseline and after treatment. RESULTS: Vitamin D3 therapy in PCOS
      patients, increased serum vitamin D (7.00 +/- 2.80 to 22.9 +/- 6.14 ng/ml),
      decreased serum total cholesterol (196.6 +/- 32.8 to 179.1 +/- 34.1 mg/dl),
      triglyceride (156.8 +/- 73.0 to 130.5 +/- 56.5 mg/dl), and VLDL (31.4 +/- 14.6 to
      26.1 +/- 11.3 mg/dl) levels significantly (p < 0.05), but it did not affect serum
      HDL-cholesterol, LDL-cholesterol, APO-AI, and hs-CRP concentrations. There was no
      change in variables in the placebo group. CONCLUSIONS: Our study showed that
      vitamin D3 therapy had beneficial effects on some CVD risk factors in PCOS
      patients with vitamin D deficiency. The trial was registered at IRCT.ir
      (IRCT138904113140N2).

PMID- 22453060
TI  - Does a 4 diagram manual enable laypersons to operate the Laryngeal Mask
      Supreme(r)? A pilot study in the manikin.
AB  - BACKGROUND: Bystander resuscitation plays an important role in lifesaving
      cardiopulmonary resuscitation (CPR). A significant reduction in the "no-flow
      time", quantitatively better chest compressions and an improved quality of
      ventilation can be demonstrated during CPR using supraglottic airway devices
      (SADs). Previous studies have demonstrated the ability of inexperienced persons
      to operate SADs after brief instruction. The aim of this pilot study was to
      determine whether an instruction manual consisting of four diagrams enables
      laypersons to operate a Laryngeal Mask Supreme(r) (LMAS) in the manikin. METHODS:
      An instruction manual of four illustrations with speech bubbles displaying the
      correct use of the LMAS was designed. Laypersons were handed a bag containing a
      LMAS, a bag mask valve device (BMV), a syringe prefilled with air and the
      instruction sheet, and were asked to perform and ventilate the manikin as
      displayed. Time to ventilation was recorded and degree of success evaluated.
      RESULTS: A total of 150 laypersons took part. Overall 145 participants (96.7%)
      inserted the LMAS in the manikin in the right direction. The device was inserted
      inverted or twisted in 13 (8.7%) attempts. Eight (5.3%) individuals recognized
      this and corrected the position. Within the first 2 minutes 119 (79.3%)
      applicants were able to insert the LMAS and provide tidal volumes greater than
      150 ml (estimated dead space). Time to insertion and first ventilation was 83.2
      +/- 29 s. No significant difference related to previous BLS training (P = 0.85),
      technical education (P = 0.07) or gender could be demonstrated (P = 0.25).
      CONCLUSION: In manikin laypersons could insert LMAS in the correct direction
      after onsite instruction by a simple manual with a high success rate. This
      indicates some basic procedural understanding and intellectual transfer in
      principle. Operating errors (n = 91) were frequently not recognized and corrected
      (n = 77). Improvements in labeling and the quality of instructional photographs
      may reduce individual error and may optimize understanding.

PMID- 22453062
TI  - Nutrient sensing and signalling by the gut.
AB  - Recent advances highlight that nutrient receptors (such as T1R1/T1R3 heterodimer,
      Ca sensing receptor and GPR93 for amino acids and protein, GPR40, GPR41, GPR43
      and GPR120 for fatty acids, T1R2/T1R3 heterodimer for monosaccharides) are
      expressed in the apical face of the gut and sense nutrients in the lumen. They
      transduce signals for the regulation of nutrient transporter expressions in the
      apical face. Interestingly, they are also localised in enteroendocrine cells
      (EEC) and mainly exert a direct control on the secretion in the lamina propria of
      gastro-intestinal peptides such as cholecystokinin, glucagon-like peptide-1 and
      peptide YY in response to energy nutrient transit and absorption in the gut. This
      informs central nuclei involved in the control of feeding such as the
      hypothalamus and nucleus of the solitary tract of the availability of these
      nutrients and thus triggers adaptive responses to maintain energy homoeostasis.
      These nutrient receptors then have a prominent position since they manage
      nutrient absorption and are principally the generator of the first signal of
      satiation mechanisms mainly transmitted to the brain by vagal afferents.
      Moreover, tastants are also able to elicit gut peptides secretion via
      chemosensory receptors expressed in EEC. Targeting these nutrient and tastant
      receptors in EEC may thus be helpful to promote satiation and so to fight
      overfeeding and its consequences.

PMID- 22453063
TI  - Timoshenko beam model for buckling of piezoelectric nanowires with surface
      effects.
AB  - This paper investigates the buckling behavior of piezoelectric nanowires under
      distributed transverse loading, within the framework of the Timoshenko beam
      theory, and in the presence of surface effects. Analytical relations are given
      for the critical force of axial buckling of nanowires by accounting for the
      effects of surface elasticity, residual surface tension, and transverse shear
      deformation. Through an example, it is shown that the critical electric potential
      of buckling depends on both the surface stresses and piezoelectricity. This study
      may be helpful in the characterization of the mechanical properties of nanowires
      and in the calibration of the nanowire-based force sensors.

PMID- 22453061
TI  - Quantitative modeling of the physiology of ascites in portal hypertension.
AB  - Although the factors involved in cirrhotic ascites have been studied for a
      century, a number of observations are not understood, including the action of
      diuretics in the treatment of ascites and the ability of the plasma-ascitic
      albumin gradient to diagnose portal hypertension. This communication presents an
      explanation of ascites based solely on pathophysiological alterations within the
      peritoneal cavity. A quantitative model is described based on experimental
      vascular and intraperitoneal pressures, lymph flow, and peritoneal space
      compliance. The model's predictions accurately mimic clinical observations in
      ascites, including the magnitude and time course of changes observed following
      paracentesis or diuretic therapy.

PMID- 22453064
TI  - Expression variation in connected recombinant populations of Arabidopsis thaliana
      highlights distinct transcriptome architectures.
AB  - BACKGROUND: Expression traits can vary quantitatively between individuals and
      have a complex inheritance. Identification of the genetics underlying transcript
      variation can help in the understanding of phenotypic variation due to genetic
      factors regulating transcript abundance and shed light into divergence patterns.
      So far, only a limited number of studies have addressed this subject in
      Arabidopsis, with contrasting results due to dissimilar statistical power. Here,
      we present the transcriptome architecture in leaf tissue of two RIL sets obtained
      from a connected-cross design involving 3 commonly used accessions. We also
      present the transcriptome architecture observed in developing seeds of a third
      independent cross. RESULTS: The utilisation of the novel R/eqtl package (which
      goal is to automatize and extend functions from the R/qtl package) allowed us to
      map 4,290 and 6,534 eQTLs in the Cvi-0 * Col-0 and Bur-0 * Col-0 recombinant
      populations respectively. In agreement with previous studies, we observed a
      larger phenotypic variance explained by eQTLs in linkage with the controlled gene
      (potentially cis-acting), compared to distant loci (acting necessarily indirectly
      or in trans). Distant eQTLs hotspots were essentially not conserved between
      crosses, but instead, cross-specific. Accounting for confounding factors using a
      probabilistic approach (VBQTL) increased the mapping resolution and the number of
      significant associations. Moreover, using local eQTLs obtained from this
      approach, we detected evidence for a directional allelic effect in genes with
      related function, where significantly more eQTLs than expected by chance were up
      regulated from one of the accessions. Primary experimental data, analysis
      parameters, eQTL results and visualisation of LOD score curves presented here are
      stored and accessible through the QTLstore service database
      http://qtlstore.versailles.inra.fr/. CONCLUSIONS: Our results demonstrate the
      extensive diversity and moderately conserved eQTL landscape between crosses and
      validate the utilisation of expression traits to explore for candidates behind
      phenotypic variation among accessions. Furthermore, this stresses the need for a
      wider spectrum of diversity to fully understand expression trait variation within
      a species.

PMID- 22453065
TI  - Local inflammatory response induced by scorpionfish Scorpaena plumieri venom in
      mice.
AB  - The Scorpaena plumieri fish venom induces a severe pain and edema, observed both
      clinically and experimentally. In order to understand more about the envenomation
      syndrome, the present study characterized experimentally the local acute
      inflammatory response induced by S. plumieri venom (SpV) in a mouse model of
      tissue injury. Our results demonstrated that the local inflammatory response
      provoked after 2 h of SpV injection in footpad of mice is characterized by
      release of pivotal pro-inflammatory mediators (TNF, IL-6 and MCP-1). These
      mediators could be associated with histopathological changes observed into paw
      tissue, characterized by cellular infiltration, mainly neutrophils. Additionally,
      an investigation of edema formation pathways involved in inflammatory response
      was performed. SpV-induced edema was reduced significantly by previous
      administration of aprotinin or icatibant (HOE-140). However, the pre-treatment
      with diclofenac sodium and promethazine had less effect on this response. These
      results demonstrate that the kallikrein-kinin system (KKS) plays a major role in
      the edema formation. Despite the whole venom hydrolyzed the kallikrein synthetic
      substrate S-2302 (Pro-Phe-Arg-pNA), its main pro-inflammatory fraction was devoid
      of kininogenase activity. Our results demonstrate that SpV evokes a complex
      inflammatory reaction stimulating a secretion of TNF, IL-6, MCP-1 and leukocytes
      recruitment at the site of venom injection. In addition provide clear evidence of
      the involvement of the KKS in inflammatory response induced by S. plumieri venom.

PMID- 22453066
TI  - Mood stabilizers for the treatment of behavioral and psychological symptoms of
      dementia: an update review.
AB  - Behavioral and psychological symptoms of dementia (BPSD) are common and
      debilitating problems, but current treatments are limited. Antipsychotic agents
      show some efficacy on BPSD, but their use is limited by the associated risk of
      cerebrovascular events and mortality. Reports have shown the efficacy of mood
      stabilizers on BPSD, but systemic reviews on this issue are scant. This article
      aims to review studies of the efficacy of mood stabilizers on BPSD, and the
      quality of the available evidence. We searched for articles published in English
      during the period 1990 to 2010 and included in the PubMed database that concerned
      treatment of BPSD with mood stabilizers, such as carbamazepine, valproate,
      gabapentin, topiramate, lamotrigine, oxcarbazepine and lithium. The quality of
      the studies was assessed by considering the trial designs, analyses, subjects and
      results. We found one meta-analysis and three randomized controlled trials (RCTs)
      supporting the efficacy of carbamazepine in managing global BPSD, particularly
      aggression and hostility. With regard to valproate, current evidence from one
      meta-analysis and five RCTs did not strongly support its efficacy for global
      BPSD, including agitation and aggression. Only open trials or case series showed
      some efficacy of gabapentin, topiramate and lamotrigine in controlling BPSD. The
      single RCT investigating the effect of oxcarbazepine on agitation and aggression
      showed negative results. Case series reports on lithium tended to show it to be
      ineffective. Thus far, among mood stabilizers, carbamazepine has the most robust
      evidence of efficacy on BPSD. More RCTs are needed to strengthen evidence
      regarding the efficacy of gabapentin, topiramate and lamotrigine. Valproate,
      oxcarbazepine and lithium showed low or no evidence of efficacy. Large and well
      designed RCTs focusing on specific symptoms of BPSD are needed to deal with the
      issue.

PMID- 22453067
TI  - Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic
      bladder cancer.
AB  - Overexpression of hypoxia-inducible factor-1 alpha is noted during the invasive
      and metastatic process of transitional cell carcinoma. It will upregulate
      vascular endothelial growth factor (VEGF) and drive proliferation, invasiveness,
      metastasis, and antiapoptotic ability of cancer cells. We proposed that tyrosine
      kinase receptor inhibitor, sunitinib malate-(Sutent; Pfizer Inc., Taiwan),
      combined with chemotherapeutic drug may present synergistic cytotoxic enhancement
      to transitional cell carcinoma cells with subsequent inhibition of their cellular
      behaviors, including proliferation, invasiveness, and metastatic activity. The
      contents of VEGF-A in mouse bladder tumor cells (MBT-2) and culture medium were
      detected by quantification-polymerase chain reaction and Western blot
      individually. The inhibitory concentrations of various chemotherapeutic drugs,
      sunitinib, and their combination treatment in MBT-2 were determined by 3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.
      Microchamber transmembrane migration assay was applied in evaluation of the
      inhibitory effects of different dosages of sunitinib and combination treatment on
      tumor cells. The cell cycle and apoptosis were analyzed after combination therapy
      by flow cytometry. Variation in apoptotic pathway was elucidated by Western blot
      using specific antibodies with cleaved PARP and caspase-3. Metastatic animal
      model mimicked by tail vein injection of MBT-2 cells was used to evaluate the
      treatment efficiency in tumor weight and survival rate. The mRNA and protein
      level of VEGF-A in MBT-2 cells increased by 70% at 48 hours interval under
      hypoxia stress condition. In MTT assay, MBT-2 cells had shown the highest
      sensitivity to epirubicin. Sunitinib combined with epirubicin had shown a
      synergistic cytotoxic effect to MBT-2 cells. Sunitinib and its combination with
      epirubicin showed significant inhibition on MBT-2 cells migration in
      microchambers. G2/M phase arrest and increased subG1 in cell cycle was seen in
      the epirubicin and sunitinib combination treatment group. The activation of
      apoptosis pathway was confirmed by increased cleaved caspase-3 and cleaved PARP
      in MBT-2 cells. In tail vein tumor inoculation C3H mice model, epirubicin alone
      and sunitinib combination therapy decreased tumor growth in lungs with marginal
      effect. Sunitinib and epirubicin combination had shown a synergistic cytotoxic
      effect and inhibited cell migration ability in MBT-2 cells. The combination can
      induce cell cycle arrest at G2/M phase and increase subG1 cells. Metastatic
      animal study also showed that sunitinib combined with epirubicin has a marginal
      effect on inhibition of tumor growth of lungs. The tyrosine kinase receptor
      inhibitor-targeted combined chemotherapy regimen may provide as a new treatment
      modality for advanced bladder cancer in the future.

PMID- 22453068
TI  - Refractive outcome of premature infants with or without retinopathy of
      prematurity at 2 years of age: a prospective controlled cohort study.
AB  - This study evaluated the extent to which refractive morbidity is correlated to
      preterm birth or retinopathy of prematurity (ROP) itself, or both, and examined
      the risk factors associated with refractive errors in a cohort of preterm infants
      with and without ROP compared with full-term infants. This longitudinal,
      prospective, controlled cohort study enrolled 109 infants, including 74 preterm
      and 35 full-term infants. Infants were divided into the following groups: no ROP,
      regressed ROP, laser-treated threshold ROP, and full-term. Cycloplegic refraction
      was determined at 6 and 24 months' corrected age. Multiple regression models,
      analysis of variance (ANOVA) with post hoc comparisons, paired t test, and the
      chi(2) test were used for data analysis. ROP status was highly predictive of
      significant refractive errors in preterm infants. Eyes with laser-treated
      threshold ROP had significant myopia at both ages (mean spherical equivalent
      [MSE] in right eye at both refractions -0.72, -1.21 diopters [D]), astigmatism
      (MSE -1.62, -1.80 D), and anisometropia (MSE 0.82, 1.02 D; ANOVA p < 0.05), and
      increased refractive errors across ages (paired t test p < 0.05). Eyes with
      regressed ROP (MSE + 0.35 D) and eyes without ROP (MSE + 0.78 D) were less
      hyperopic than the controls (MSE + 1.60 D) before 1 year (post hoc comparisons p
      < 0.05). After 1 year, however, hyperopic status, astigmatism, and anisometropia
      were similar to eyes with regressed ROP (MSE + 0.38 D, astigmatism -0.94 D,
      anisometropia 0.32 D), eyes without ROP (MSE + 0.35 D, astigmatism -0.51 D,
      anisometropia 0.31 D) and the controls (MSE + 0.72 D, astigmatism -0.59 D,
      anisometropia 0.50 D) by post hoc comparisons (p > 0.05). Thus, the persistent
      hyperopic status across ages in patients with regressed ROP and in patients
      without ROP differed significantly (paired t test p > 0.05) from that in the full
      term infants, with a reduction in hypermetropia noted for the first 2 years of
      life (paired t test p < 0.05). The incidence and magnitude of significant
      refractive errors increased with severe ROP and with age. Although the
      emmetropization process of preterm birth, including regressed ROP and no ROP,
      differed from full-term birth in early infancy, we found no differences in the
      refractive status after 1 year in patients with regressed ROP and in patients
      without ROP, who were at risk of developing ametropia similar to that of full
      term patients. Therefore, apart from laser-treated ROP, children with regressed
      ROP and without ROP can likely be observed with a verbal vision screening at 3-4
      years of age.

PMID- 22453069
TI  - Clinical experience in diagnosis and treatment of malignant gastrointestinal
      stromal tumors.
AB  - This study investigated the clinical pathologic character of malignant
      gastrointestinal stromal tumors (MGIST), their treatment with surgery, and
      evaluated the efficacy of imatinib postoperation. A total of 68 MGIST patients
      were enrolled. Of these, 27 patients underwent imatinib auxiliary therapy
      (treatment group) and 41 underwent imatinib therapy (control group). The
      therapeutic effects on the two groups were compared using chi(2) test analysis
      after follow-up of two years. The expressions of CD117, CD34, S100, Vimentin, and
      alpha smooth-muscle actin (SMA) were detected by immunohistochemistry methods. Of
      the 68 cases, 28 showed potential MGIST, whereas 40 had MGIST. Haemorrhagia or
      necrosis, abundant cell, manifest heteromorphism, and caryocinesia were observed
      in varying degrees. The positive rates of CD117, CD34, Vimentin, S100, and SMA
      were 89.7% (61/62), 88.2% (60/62), 73.5% (50/62), 41.1% (28/62) and 25.0%
      (17/62), respectively. The recurrence rate in the treatment group was
      significantly lower than that in the control group (p < 0.01). We concluded that
      CD117 and CD34 may be the most valuable markers in the diagnosis of MGIST, and
      the diagnosis of MGIST depends on the pathology. Surgery is a far better approach
      in the treatment of such patients, and imatinib is the more efficient target drug
      in preventing recurrence and metastasis.

PMID- 22453070
TI  - Soft-tissue profile changes after orthognathic surgery of mandibular prognathism.
AB  - During surgical correction of facial deformities, accurate prediction of the
      resulting facial profile is important for the patient and the surgeon. The
      purpose of the present study was to investigate profile changes after surgical
      treatment of mandibular prognathism. Thirty patients (20 females and 10 males;
      ages 17-28 years) with mandibular prognathism underwent vertical ramus osteotomy.
      Preoperative and postoperative cephalograms were analyzed; landmarks were
      identified and compared. The mean horizontal setback of the pogonion (Pog) was
      11.7 mm. The setback ratios of labrale inferius (Li)/incision inferius (Ii),
      labiomental sulcus (Si)/point B, and soft tissue pogonion (PogS)/pogonion (Pog)
      were 0.98, 0.99, and 0.95, respectively. There were no sex-related changes in
      soft tissue. These findings indicate that changes in soft tissue closely
      correlate with the amount of mandibular setback in the horizontal direction. Such
      information might facilitate more accurate prediction of the outcome of
      orthognathic surgery.

PMID- 22453071
TI  - Inlay buccal mucosal graft for reoperative posterior urethroplasty.
AB  - Posterior urethral distraction injury following major pelvic trauma is a surgical
      challenge. Although rarely seen, cases of failure after formal urethral
      reconstruction are even more problematic. We adapted the concept of augmented
      free buccal mucosal grafts, which have been successful in anterior urethroplasty,
      for repairing the posterior urethra in these rare cases with the aim of reducing
      the likelihood of penile chordee postoperatively. During 2007-2009, four patients
      were candidates for the proposed procedure because they had received formal
      transperineal urethral reconstruction but were unable to urinate through the
      urethra. The urethra was approached transperineally and opened in the midline,
      rather than divided. Buccal mucosal grafts of an appropriate size were placed in
      the created urethral groove from 4- to 8 o'clock in the lithotomy view. After the
      procedure, the urethral catheter was kept for 3 weeks. All patients voided
      through the urethra after the procedure. The maximal postoperative urinary flow
      rates were between 12-15 ml/seconds in all cases for a follow-up period of 18-30
      months. The recurrence rate was 50% (2/4). Recurrent strictures were minor, and
      they showed a web-like stricture ring near the suture line. Restricture within 6
      months of surgery responded well to endoscopic internal urethrotomy plus
      dilatations. In conclusion, without further compromising urethral length,
      reoperative posterior urethroplasty with the inlay grafting technique can be
      considered in selective cases.

PMID- 22453072
TI  - The Chinese version of the Severity of Dependence Scale as a screening tool for
      benzodiazepine dependence in Taiwan.
AB  - The development of an instrument to estimate the incidence, characteristics, and
      risk factors of benzodiazepine (BZD) dependence broadly in Taiwan is an important
      task. This study assessed the validity of the Chinese version of the Severity of
      Dependence Scale (SDS([Ch])) among regular BZD users in Taiwan (n=228). A
      positive correlation was shown between SDS([Ch]) and Mini-International
      Neuropsychiatric Interview diagnosed of BZD dependence. Thirty-six percent of the
      users received a Mini-International Neuropsychiatric Interview diagnosis of
      current BZD dependence. The dependent users tended to be divorced/widowed; not
      schizophrenic; and have higher SDS([Ch]) scores, a longer duration of use, and
      multiple-BZD use. The SDS([Ch]) for BZD dependence was shown to have high
      diagnostic utility (area under the receiver operating characteristic
      curve=0.779), a sensitivity of 80.5%, and a specificity of 85.7%, with a cutoff
      point of 7. The findings support that the SDS([Ch]) is a valid brief self
      reported questionnaire for the assessment of BZD dependence among chronic users
      in Taiwan.

PMID- 22453073
TI  - A novel SRD5A2 mutation in a Taiwanese newborn with ambiguous genitalia.
AB  - The 5alpha-reductase type 2 deficiency is a rare autosomal recessive 46,XY
      disorder of sex development caused by the mutated 5alpha-reductase type 2
      (SRD5A2) gene. In this disease, defective conversion of testosterone to
      dihydrotestosterone leads to variable presentations of male ambiguous genitalia
      during fetal development. The most crucial clinical decision for the affected
      individual is proper gender assignment; therefore, a prompt and correct diagnosis
      is important. In this present study, we report a normal male karyotype
      manifesting microphallus, bifid scrotum/labia majora with bilateral palpable
      gonads, and a blind-ended pseudovagina. The mutation analysis of the SRD5A2 gene
      revealed one novel C to T transition changing glutamine to a stop codon at codon
      71 (p.Q71X) in exon 1 and one known G to A transition changing arginine to
      glutamine at codon 227 (p.R227Q) in exon 4. The p.Q71X mutation presumably
      results in a truncated protein, while the p.R227Q mutation is conceived to impair
      enzyme function and has been reported in patients of East Asian descent. This
      report demonstrates the essential role of hormonal and molecular studies for
      genetic counseling and gender assignment in males with pseudovaginal disorder of
      sex development, and our report helps identify a novel SRD5A2 gene mutation in
      the Taiwanese population.

PMID- 22453074
TI  - Myelodysplasia followed by Good's Syndrome: a unique manifestation associated
      with thymoma.
AB  - Good's syndrome, also known as thymoma with combined immunodeficiency, is rare.
      The immunodeficiency may precede, arise concurrently with or follow the diagnosis
      of thymoma. In addition to myasthenia gravis and Good's syndrome, paraneoplastic
      syndromes associated with thymoma can also be manifested with hematological
      disorders, such as pure red cell aplasia, aplastic anemia, agranulocytosis,
      hemolytic anemia, pernicious anemia, and paroxysmal nocturnal hemoglobinuria.
      Myelodysplastic syndrome is a group of clonal hematopoietic stem cell diseases
      characterized by cytopenia(s), dysplasia in one or more lineages, ineffective
      hematopoiesis, and potential precursors of acute leukemia. One proposed
      pathogenesis of myelodysplasia is autoantibodies that directly reject against
      hematopoietic cells, but this situation is rare in thymoma. Herein, we report a
      thymoma patient with unique paraneoplastic syndromes who developed myelodysplasia
      prior to Good's syndrome. Early and accurate diagnosis of myelodysplastic
      syndrome is important for disease management, especially in patients whose
      myelodysplastic syndrome is possibly derived from autoimmunity. For thymoma
      patients with recurrent infections, comprehensive immunologic studies to exclude
      the possibility of Good's syndrome and prophylactic intravenous immunoglobulin
      infusion in suitable candidates are warranted.

PMID- 22453075
TI  - Hereditary hemorrhagic telangiectasia presenting as portal hypertension.

PMID- 22453076
TI  - Fasting capillary blood glucose: an appropriate measurement in screening for
      diabetes and pre-diabetes in low-resource rural settings.
AB  - OBJECTIVE: To evaluate the efficiency of fasting capillary blood glucose (FCG)
      measurement as compared with fasting venous plasma glucose (FPG) measurement in
      screening diabetes and pre-diabetes in low-resource rural settings. SUBJECTS AND
      METHODS: In 2010, 993 participants were randomly selected from 9 villages in
      Yunnan province using cluster sampling method. Samples for FCG and FPG test were
      obtained after demographics and physical examination. The oral glucose tolerance
      test was performed in parallel as gold standard for diagnosis. Diagnostic
      capacities of the FCG measurement in predicting undiagnosed diabetes and pre
      diabetes were assessed. The performance of FCG and FPG tests was compared.
      RESULTS: Fifty-seven individuals with undiagnosed diabetes and 145 subjects with
      pre-diabetes were detected. The concordance between FCG and FPG levels was high
      (r = 0.75, p < 0.001). The area under the curve (AUC) for FCG test in predicting
      diabetes was 0.88 [95% confidence interval (CI) 0.82-0.93] with the optimal
      cutoff value of 5.65 mmol/l, sensitivity of 84.2%, and specificity of 79.3%. The
      corresponding values in FPG tests were 0.92 (95% CI 0.88-0.97) (AUC), 6.51 mmol/l
      (optimal cutoff point), 82.5% (sensitivity) and 98.3% (specificity),
      respectively. No significant difference was found in the AUC for the two
      screening strategies. CONCLUSION: FCG measurement is considered to be a
      convenient, practicable screening method in low-resource rural communities with
      acceptable test properties.

PMID- 22453077
TI  - FIRE (Facilitating Implementation of Research Evidence): a study protocol.
AB  - BACKGROUND: Research evidence underpins best practice, but is not always used in
      healthcare. The Promoting Action on Research Implementation in Health Services
      (PARIHS) framework suggests that the nature of evidence, the context in which it
      is used, and whether those trying to use evidence are helped (or facilitated)
      affect the use of evidence. Urinary incontinence has a major effect on quality of
      life of older people, has a high prevalence, and is a key priority within
      European health and social care policy. Improving continence care has the
      potential to improve the quality of life for older people and reduce the costs
      associated with providing incontinence aids. OBJECTIVES: This study aims to
      advance understanding about the contribution facilitation can make to
      implementing research findings into practice via: extending current knowledge of
      facilitation as a process for translating research evidence into practice;
      evaluating the feasibility, effectiveness, and cost-effectiveness of two
      different models of facilitation in promoting the uptake of research evidence on
      continence management; assessing the impact of contextual factors on the
      processes and outcomes of implementation; and implementing a pro-active knowledge
      transfer and dissemination strategy to diffuse study findings to a wide policy
      and practice community. SETTING AND SAMPLE: Four European countries, each with
      six long-term nursing care sites (total 24 sites) for people aged 60 years and
      over with documented urinary incontinence METHODS AND DESIGN: Pragmatic
      randomised controlled trial with three arms (standard dissemination and two
      different programmes of facilitation), with embedded process and economic
      evaluation. The primary outcome is compliance with the continence
      recommendations. Secondary outcomes include proportion of residents with
      incontinence, incidence of incontinence-related dermatitis, urinary tract
      infections, and quality of life. Outcomes are assessed at baseline, then at 6,
      12, 18, and 24 months after the start of the facilitation interventions. Detailed
      contextual and process data are collected throughout, using interviews with
      staff, residents and next of kin, observations, assessment of context using the
      Alberta Context Tool, and documentary evidence. A realistic evaluation framework
      is used to develop explanatory theory about what works for whom in what
      circumstances. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11598502.

PMID- 22453078
TI  - Large-scale survey for novel genotypes of Plasmodium falciparum chloroquine
      resistance gene pfcrt.
AB  - BACKGROUND: In Plasmodium falciparum, resistance to chloroquine (CQ) is conferred
      by a K to T mutation at amino acid position 76 (K76T) in the P. falciparum CQ
      transporter (PfCRT). To date, at least 15 pfcrt genotypes, which are represented
      by combinations of five amino acids at positions 72-76, have been described in
      field isolates from various endemic regions. To identify novel mutant pfcrt
      genotypes and to reveal the genetic relatedness of pfcrt genotypes, a large-scale
      survey over a wide geographic area was performed. METHODS: Sequences for exon 2
      in pfcrt, including known polymorphic sites at amino acid positions 72, 74, 75
      and 76, were obtained from 256 P. falciparum isolates collected from eight
      endemic countries in Asia (Bangladesh, Cambodia, Lao P.D.R., the Philippines and
      Thailand), Melanesia (Papua New Guinea and Vanuatu) and Africa (Ghana). A
      haplotype network was constructed based on six microsatellite markers located -29
      kb to 24 kb from pfcrt in order to examine the genetic relatedness among mutant
      pfcrt genotypes. RESULTS: In addition to wild type (CVMNK at positions 72-76),
      four mutant pfcrt were identified; CVIET, CVIDT, SVMNT and CVMNT (mutated amino
      acids underlined). Haplotype network revealed that there were only three mutant
      pfcrt lineages, originating in Indochina, Philippines and Melanesia. Importantly,
      the Indochina lineage contained two mutant pfcrt genotypes, CVIET (n = 95) and
      CVIDT (n = 14), indicating that CVIDT shares a common origin with CVIET.
      Similarly, one major haplotype in the Melanesian lineage contained two pfcrt
      genotypes; SVMNT (n = 71) and CVMNT (n = 3). In Africa, all mutant pfcrt
      genotypes were the CVIET of the Indochina lineage, probably resulting from the
      intercontinental migration of CQ resistance from Southeast Asia. CONCLUSIONS: The
      number of CQ-mutant lineages observed in this study was identical to that found
      in previous studies. This supports the hypothesis that the emergence of novel CQ
      resistance is rare. However, in the mutant pfcrt genotypes, amino acid changes at
      positions 72, 74 and 75 appear to have recently been generated at least several
      times, producing distinct pfcrt mutant genotypes. The occurrence of new mutations
      flanking K76T may yield stronger resistance to CQ and/or a higher fitness than
      the original pfcrt mutant.

PMID- 22453079
TI  - Developmental changes of aldehyde oxidase activity and protein expression in
      human liver cytosol.
AB  - Aldehyde oxidase (AO) plays a role in metabolizing many drugs, such as
      methotrexate and 6-mercaptopurine. We previously showed that AO activity in rat
      liver rapidly increases from birth, reaching a plateau within 4 weeks, and is
      regulated at the protein expression level. However, developmental changes of AO
      activity and protein expression in human liver have not been reported. Here, we
      investigated the developmental changes and variability of AO in 16 human livers
      (13 children ranging from 13 days to 12 years old and 3 adults, 17, 34 and 45
      years old). Young children (13 days to 4 months after birth) showed little liver
      AO activity, evaluated in terms of the activities for oxidation of N-1
      methylnicotinamide to N-1-methyl-2-pyridone-5-carboxamide and N-1-methyl-4
      pyridone-3-carboxamide in liver cytosol. However, these oxidase activities were
      markedly increased after 4 months, reaching the adult level by about 2 years of
      age. The AO band density in immunoblotting analysis was well correlated with the
      AO activity among all subjects (p < 0.01, r(2) = 0.771). Therefore, AO activity
      in the liver of young children is regulated at the AO protein expression level.
      Thus, as in rats, the AO activity in humans rapidly increases soon after birth,
      and is regulated at the protein expression level.

PMID- 22453080
TI  - Structure-activity relationship modeling for predicting interactions with
      pregnane X receptor by recursive partitioning.
AB  - Pregnane X receptor (PXR) is a ligand-activated nuclear factor that upregulates
      the expression of proteins involved in the detoxification and clearance of
      xenobiotics, primarily cytochrome P450 3A4 (CYP3A4). Structure-activity
      relationship (SAR) analysis of PXR agonists is useful for avoiding unwanted
      pharmacokinetics due to drug-drug interactions. To perform large-scale ligand
      based SAR modeling, we systematically collected information on chemical-PXR
      interactions from the PubMed database by using the text mining system we
      developed, and merged it with screening data registered in the PubChem BioAssay
      database and other published data. Curation of the data resulted in 270 human PXR
      agonists and 248 non-agonists. After the entire data set was divided into
      training and testing data sets, the training data set comprising 415 data entries
      (217 positive and 198 negative instances) was analyzed by a recursive
      partitioning method. The classification tree optimized by a cross-validation
      pruning algorithm gave an accuracy of 79.0%, and, for the external testing data
      set, could correctly classify PXR agonists and non-agonists at an accuracy of
      70.9%. Descriptors chosen as splitting rules in the classification tree were
      generally associated with electronic properties of molecules, suggesting they had
      an important role in the modes of interaction.

PMID- 22453081
TI  - Micro-computed tomography assessment of the progression of fracture healing in
      mice.
AB  - The mouse fracture model is ideal for research into the pathways of healing
      because of the availability of genetic and transgenic mice and the ability to
      create cell-specific genetic mutations. While biomechanical tests and histology
      are available to assess callus integrity and tissue differentiation,
      respectively, micro-computed tomography (MUCT) analysis has increasingly been
      utilized in fracture studies because it is non-destructive and provides
      descriptions of the structural and compositional properties of the callus.
      However, the dynamic changes of MUCT properties that occur during healing are not
      well defined. Thus, the purpose of this study was to determine which MUCT
      properties change with the progression of fracture repair and converge to values
      similar to unfractured bone in the mouse femur fracture model. A unilateral femur
      fracture was performed in C57BL/6 mice and intramedullary fixation performed.
      Fractured and un-fractured contralateral specimens were harvested from groups of
      mice between 2 and 12 weeks post-fracture. Parameters describing callus based on
      MUCT were obtained, including polar moment of inertia (J), bending moment of
      inertia (I), total volume (TV), tissue mineral density (TMD), total bone volume
      fraction (BV/TV), and volumetric bone mineral density (vBMD). For comparison,
      plain radiographs were used to measure the callus diameter (D) and area (A); and
      biomechanical properties were evaluated using either three-point bending or
      torsion. The MUCT parameters J, I, TV, and TMD converged toward their respective
      values of the un-fractured femurs over time, although significant differences
      existed between the two sides at every time point evaluated (p<0.05). Radiograph
      measurement D changed with repair progression in similar manner to TV. In
      contrast, BV/TV and BMD increased and decreased over time with statistical
      differences between callus and un-fractured bone occurring sporadically.
      Similarly, none of the biomechanical properties were found to distinguish
      consistently between the fractured and un-fractured femur. Micro-CT parameters
      assessing callus structure and size (J, I, and TV) were more sensitive to changes
      in callus over time post-fracture than those assessing callus substance (TMD,
      BV/TV, and BMD). Sample size estimates based on these results indicate that
      utilization of MUCT requires fewer animals than biomechanics and thus is more
      practical for evaluating the healing femur in the mouse fracture model.

PMID- 22453083
TI  - Editorial.

PMID- 22453082
TI  - ATM-dependent phosphorylation of the checkpoint clamp regulates repair pathways
      and maintains genomic stability.
AB  - Upon genotoxic stress and during normal S phase, ATM phosphorylates the
      checkpoint clamp protein Rad9 in a manner that depends on Ser272. Ser272 is the
      only known ATM-dependent phosphorylation site in human Rad9. However, Ser272
      phosphorylation is not required for survival or checkpoint activation after DNA
      damage. The physiological function of Ser272 remains elusive. Here, we show that
      ATM-dependent Rad9(Ser272) phosphorylation requires the MRN complex and controls
      repair pathways. Furthermore, the mutant cells accumulate large numbers of
      chromosome breaks and induce gross chromosomal rearrangements. Our findings
      establish a new and unexpected role for ATM: it phosphorylates the checkpoint
      clamp in order to control repair pathways, thereby maintaining genomic integrity
      during unperturbed cell cycle and upon DNA damage.

PMID- 22453084
TI  - The Evolution of a Specialty Society: AUGS: Thirty Years in the Making.

PMID- 22453085
TI  - Surgery for pelvic organ prolapse.
AB  - OBJECTIVES: : Surgery for pelvic organ prolapse (POP) is common with increasing
      high-quality evidence to guide surgical practice. Yet many important basic
      questions remain, including the optimal timing for POP surgery, the optimal
      preoperative evaluation of urinary tract function, and the postoperative outcome
      assessment. This manuscript reviews traditional surgical approaches for POP.
      METHODS: : Formal and hand-searching of prolapse literature was conducted by the
      committee on Pelvic Organ Prolapse Surgery for the most recent International
      Consultation on Incontinence. The committee (authors) was composed of prolapse
      specialists from around the world. Consensus recommendations were made following
      literature abstraction. RESULTS: : Surgical correction of POP can be divided into
      2 main categories as follows: reconstructive procedures to correct anterior and
      posterior wall defects and resuspend the vaginal apex or obliterative procedures
      to close off the vagina. Reconstructive surgery may use the vaginal route or the
      abdominal route. CONCLUSIONS: : In addition to recommendations within the report,
      the committee reaffirms that in planning surgery, the individual patient's risk
      for surgery, risk of recurrence, previous treatments, and surgical goals are all
      considered in deciding on obliterative versus reconstructive procedures, and in
      deciding whether the vaginal or the abdominal approach will be used for
      reconstructive repairs.

PMID- 22453086
TI  - The impact of cesarean delivery on pelvic floor dysfunction in lysyl oxidase like
      1 knockout mice.
AB  - OBJECTIVE: : Lysyl oxidase like-1 (LOXL1) knockout mice have abnormal elastic
      fiber homeostasis and frequently develop pelvic floor dysfunction after pregnancy
      and delivery. The objective of this study was to test the hypothesis that tissue
      changes associated with vaginal delivery lead to pelvic floor dysfunction as a
      result of abnormal elastic fiber homeostasis. METHODS: : Female LOXL1 knockout
      mice delivered either spontaneously or by cesarean delivery. Mice were assessed
      weekly for pelvic organ prolapse (POP). At 12 weeks postpartum, lower urinary
      tract function was assessed by cystometry and leak-point pressure testing.
      Urethrovaginal cross-sections were analyzed using a histologic grading scale to
      assess elastin fiber disorganization. RESULTS: : A total of 39 mice delivered by
      spontaneous vaginal delivery and 36 by cesarean delivery. Twelve weeks after
      spontaneous vaginal delivery or cesarean delivery, 23 (59%) and 11 (31%) mice had
      developed POP, respectively. The mean time to develop POP was 7.2 weeks after
      spontaneous vaginal delivery and 10.5 weeks after cesarean delivery (log rank, P
      = 0.0008). The Cox proportional hazard ratio was 0.55 (95% confidence interval,
      0.38-0.79). Mice with POP had increased frequency of bladder contractions not
      associated with voiding during cystometry (P = 0.02). POP, but not mode of
      delivery, was associated with increased elastic fiber disorganization.
      CONCLUSIONS: : Cesarean delivery delays the development of POP in LOXL1 knockout
      mice. POP is associated with increased bladder contraction frequency and
      increased elastic fiber disorganization in the urethra and vagina. The mechanisms
      underlying these findings warrant further investigation.

PMID- 22453087
TI  - Sexual function in women with overactive bladder.
AB  - OBJECTIVES: : Overactive bladder (OAB) is a major cause of suffering in many
      patients, requiring long-term therapy to maintain symptoms relief. Incontinence
      or even the fear of leaking urine interferes with sexual function. However,
      studies evaluating the burden of OAB on female sexual function are limited. The
      aim of this study was to assess the prevalence of sexual dysfunction among women
      with OAB compared with healthy controls. METHODS: : A total of 112 female
      patients with clinical and urodynamically proven OAB and 165 healthy controls,
      free from urinary symptoms were included in our study. Women younger than 18 or
      sexually inactive were excluded, while the 2 groups were matched to age, parity,
      and menopause status. All women were investigated in accordance with the Female
      Sexual Function Index (FSFI) which contains 19 questions and categorizes sexual
      dysfunction in 6 domains. RESULTS: : According to FSFI, and using as a cut off
      score, the value of 26.5, sexual dysfunction was diagnosed in 47% of urge
      incontinent women compared with 22% among healthy controls. We noticed that from
      the incontinent women with FSFI score lower than 26.5, 47% reported sexual pain
      disorders, 34% hypoactive sexual desire, 25% sexual arousal disorders, 25%
      lubrication disorder, and 22% complained of orgasmic deficiency. Furthermore 6 of
      10 women with sexual arousal disorders and 10 of 15 with sexual pain disorders
      also complained for recurrent bacterial cystitis. The FSFI median values in both
      groups scored as follows (patients vs. controls: median value): desire: 2.9
      versus 4.4; arousal: 2.9 versus 4.5; lubrication: 3.3 versus 4.6; orgasm: 3.5
      versus 4.3; sexual satisfaction: 2.9 versus 4.4; sexual pain: 2.8 versus 4.3 and
      full scale 18.3 versus 26.5 (P < 0.001). CONCLUSIONS: : Women with OAB reported
      sexual dysfunction in a considerably higher number than a general, healthy female
      population without urinary symptoms.

PMID- 22453088
TI  - The Association Between Stage II or Greater Posterior Prolapse and Bothersome
      Obstructive Bowel Symptoms.
AB  - OBJECTIVE: : The primary objective of this study was to estimate the association
      between stage II or greater posterior prolapse and individual obstructive bowel
      symptoms. METHODS: : We conducted a cross-sectional study of all women presenting
      for initial visit at a tertiary center for pelvic floor disorders. Exposure was
      defined as stage II or greater posterior vaginal prolapse as measured by pelvic
      organ prolapse quantification measurements. Outcomes included the separate
      bothersome obstructive bowel symptoms of splinting, straining, or incomplete
      bowel emptying. RESULTS: : Our study included 721 women. Univariate analysis did
      not show an association between stage II or greater posterior prolapse and the
      bothersome symptoms of straining or incomplete emptying. Stage II or greater
      posterior prolapse was associated with bothersome splinting (adjusted OR, 1.63;
      95% CI, 1.06-2.53). CONCLUSIONS: : Stage II or greater posterior prolapse was
      associated with the bothersome symptom of splinting, but not bothersome straining
      or the sensation of incomplete evacuation.

PMID- 22453089
TI  - Attributes of successful and unsuccessful female pelvic medicine and
      reconstructive surgery fellowship applicants.
AB  - OBJECTIVE: : To evaluate qualifications of successful applicants to Female Pelvic
      Medicine and Reconstructive Surgery (FPMRS) fellowship programs. METHODS: : A 55
      point web-based survey was sent to 49 applicants participating in the 2008 FPMRS
      Match. RESULTS: : The survey achieved a 59% response rate, with a total of 29
      respondents. Regarding prematch educational preparations pursued by applicants,
      11 of the 24 matched respondents (46%) trained at residencies that offered FPMRS
      fellowship training. About 19 matched applicants (19/21, 90%) and 2 unmatched
      applicants (2/5, 40%) received a letter of recommendation from a "nationally
      known" female pelvic medicine surgeon. About 40% of matched and unmatched
      applicants authored at least one manuscript. CONCLUSIONS: : If these respondents
      are representative of all fellowship candidates in FPMRS match, then it would be
      expected that combined application costs for all candidates would be almost
      $350,000.

PMID- 22453090
TI  - Cartilaginous symphysis pubis cysts: report of two cases, technique for removal,
      and review of the literature.
AB  - Cartilaginous symphysis pubis cysts are rare. There are 7 cases previously
      reported in the literature. Patients are commonly asymptomatic or may present
      with a slow-growing, painless vulvar mass, voiding difficulty, and/or
      dyspareunia. Two cases were managed at our center over 5 years. We present these
      2 cases, a surgical technique for removal, a summary of all reported cases, and
      some perspectives on the pathophysiologic mechanisms for the origin of this
      lesion.

PMID- 22453092
TI  - Mabs's communication networks.

PMID- 22453091
TI  - IBC's 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics
      International Conferences and the 2011 Annual Meeting of The Antibody Society,
      December 5-8, 2011, San Diego, CA.
AB  - The 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics
      international conferences, and the 2011 Annual Meeting of The Antibody Society,
      organized by IBC Life Sciences with contributions from The Antibody Society and
      two Scientific Advisory Boards, were held December 5-8, 2011 in San Diego, CA.
      The meeting drew ~800 participants who attended sessions on a wide variety of
      topics relevant to antibody research and development. As a preview to the main
      events, a pre-conference workshop held on December 4, 2011 focused on antibodies
      as probes of structure. The Antibody Engineering Conference comprised eight
      sessions: (1) structure and dynamics of antibodies and their membrane receptor
      targets; (2) model-guided generation of binding sites; (3) novel selection
      strategies; (4) antibodies in a complex environment: targeting intracellular and
      misfolded proteins; (5) rational vaccine design; (6) viral retargeting with
      engineered binding molecules; (7) the biology behind potential blockbuster
      antibodies and (8) antibodies as signaling modifiers: where did we go right, and
      can we learn from success? The Antibody Therapeutics session comprised five
      sessions: (1)Twenty-five years of therapeutic antibodies: lessons learned and
      future challenges; (2) preclinical and early stage development of antibody
      therapeutics; (3) next generation anti-angiogenics; (4) updates of clinical stage
      antibody therapeutics and (5) antibody drug conjugates and bispecific antibodies.

PMID- 22453093
TI  - 7th annual European Antibody Congress 2011: November 29-December 1, 2011, Geneva,
      Switzerland.
AB  - The 7th European Antibody Congress (EAC), organized by Terrapin Ltd., was again
      held in Geneva, Switzerland, following on the tradition established with the 4th
      EAC. The 2011 version of the EAC was attended by nearly 250 delegates who learned
      of the latest advances and trends in the global development of antibody-based
      therapeutics. The first day focused on advances in understanding structure
      function relationships, choosing the best format, glycoengineering biobetter
      antibodies, improving the efficacy and drugability of mAbs and epitope mapping.
      On the second day, the discovery of novel targets for mAb therapy, clinical
      pipeline updates, use of antibody combinations to address resistance, generation
      and identification of mAbs against new targets and biosimilar mAb development
      were discussed. Antibody-drug conjugates, domain antibodies and new scaffolds and
      bispecific antibodies were the topics of the third day. In total, nearly 50
      speakers provided updates of programs related to antibody research and
      development on-going in the academic, government and commercial sectors.

PMID- 22453095
TI  - Monoclonal antibodies directed against human FcRn and their applications.
AB  - The MHC class I-like Fc receptor (FcRn) is an intracellular trafficking Fc
      receptor that is uniquely responsible for the extended serum half-life of
      antibodies of the IgG subclass and their ability to transport across cellular
      barriers. By performing these functions, FcRn affects numerous facets of antibody
      biology and pathobiology. Its critical role in controlling IgG pharmacokinetics
      has been leveraged for the design of therapeutic antibodies and related
      biologics. FcRn also traffics serum albumin and is responsible for the enhanced
      pharmacokinetic properties of albumin-conjugated therapeutics. The understanding
      of FcRn and its therapeutic applications has been limited by a paucity of
      reliable serological reagents against human FcRn. Here, we describe the
      properties of a new panel of highly specific monoclonal antibodies (mAbs)
      directed against human FcRn with diverse epitope specificities. We show that this
      antibody panel can be used to study the tissue expression pattern of human FcRn,
      to selectively block IgG and serum albumin binding to human FcRn in vitro and to
      inhibit FcRn function in vivo. This mAb panel provides a powerful resource for
      probing the biology of human FcRn and for the evaluation of therapeutic FcRn
      blockade strategies. 

PMID- 22453097
TI  - The Cabilly patents: status quo and relevance for antibody companies.
AB  - This article discusses the status quo of the Cabilly patents, their scope of
      protection and the role these patents play for the therapeutic antibody industry
      in Europe and the US. 

PMID- 22453096
TI  - Minipig as a potential translatable model for monoclonal antibody
      pharmacokinetics after intravenous and subcutaneous administration.
AB  - Subcutaneous (SC) delivery is a common route of administration for therapeutic
      monoclonal antibodies (mAbs) with pharmacokinetic (PK)/pharmacodynamic (PD)
      properties requiring long-term or frequent drug administration. An ideal in vivo
      preclinical model for predicting human PK following SC administration may be one
      in which the skin and overall physiological characteristics are similar to that
      of humans. In this study, the PK properties of a series of therapeutic mAbs
      following intravenous (IV) and SC administration in Gottingen minipigs were
      compared with data obtained previously from humans. The present studies
      demonstrated: (1) minipig is predictive of human linear clearance; (2) the SC
      bioavailabilities in minipigs are weakly correlated with those in human; (3)
      minipig mAb SC absorption rates are generally higher than those in human and (4)
      the SC bioavailability appears to correlate with systemic clearance in minipigs.
      Given the important role of the neonatal Fc-receptor (FcRn) in the PK of mAbs,
      the in vitro binding affinities of these IgGs against porcine, human and
      cynomolgus monkey FcRn were tested. The result showed comparable FcRn binding
      affinities across species. Further, mAbs with higher isoelectric point tended to
      have faster systemic clearance and lower SC bioavailability in both minipig and
      human. Taken together, these data lend increased support for the use of the
      minipig as an alternative predictive model for human IV and SC PK of mAbs. 

PMID- 22453098
TI  - Improved stability of multivalent antibodies containing the human collagen XV
      trimerization domain.
AB  - We recently described the in vitro and in vivo properties of an engineered
      homotrimeric antibody made by fusing the N-terminal trimerization region of
      collagen XVIII NC1 domain to the C-terminus of a scFv fragment [trimerbody (scFv
      NC1) 3; 110 kDa]. Here, we demonstrated the utility of the N-terminal
      trimerization region of collagen XV NC1 domain in the engineering of trivalent
      antibodies. We constructed several scFv-based trimerbodies containing the human
      type XV trimerization domain and demonstrated that all the purified trimerbodies
      were trimeric in solution and exhibited excellent antigen binding capacity.
      Importantly, type XV trimerbodies demonstrated substantially greater thermal and
      serum stability and resistance to protease digestion than type XVIII
      trimerbodies. In summary, the small size, high expression level, solubility and
      stability of the trimerization domain of type XV collagen make it the ideal
      choice for engineering homotrimeric antibodies for cancer detection and therapy. 

PMID- 22453099
TI  - Pharmacokinetics and tolerability of human mouse chimeric anti-CD22 monoclonal
      antibody in Chinese patients with CD22-positive non-Hodgkin lymphoma.
AB  - The safety and pharmacokinetics assessment of antibodies targeting CD22 (e.g.,
      epratuzumab) have been established in western Caucasian populations, but there
      are no reports of the effects in Chinese populations. This dose-escalation study
      examines the safety, pharmacokinetics and biologic effects of multiple doses of
      anti-CD22 human-murine chimeric monoclonal antibody SM03 in 21 Chinese patients
      with CD22-positive non-Hodgkin lymphoma. Most of drug-related adverse events
      (AEs) were mild and reversible. Two patients experienced serious AEs
      (hemorrhage); one patient had grade 4 neutropenia; one patient had asymptomatic
      grade III prolongation of activated partial thromboplastin time (APTT). Major AEs
      included fever (71%), prolongation of APTT (42.8%), leukocytopenia (44.4%),
      alanine transaminase elevation (28.6%), elevated serum creatinine (23.8%) and
      injection site skin redness (14.3%). Circulating B cells transiently decreased
      without significant effects on T cells or immunoglobulin levels. Pharmacokinetic
      data revealed that mean maximum observed SM03 concentration and mean AUC from
      time zero to infinity increased in a dose-dependent manner up to 360 mg/m (2)
      SM03. Mean clearance was similar at doses <= 360 mg/m (2) and decreased
      significantly at dose 480 mg/m (2), supporting saturation of B-cell binding at
      360 mg/m (2). Across all dose levels and histologies, one patient achieved
      partial response at 480 mg/m (2) dose; 14 patients had stable disease as best
      response and four patients progressed. Overall, SM03 was tolerated at doses
      ranging from 60-480 mg/m (2) and had potential efficacy in Chinese patients with
      follicular lymphoma.

PMID- 22453102
TI  - Gynecologic surgical training.

PMID- 22453103
TI  - Assessing current trends in resident hysterectomy training.
AB  - OBJECTIVES: : Our survey assessed the current trends in hysterectomy experience
      in US obstetrics and gynecology (OG) residency programs and residents' and
      program directors' perceptions of robotic surgery's effect on surgical training.
      METHODS: : An online survey was e-mailed to program directors and graduating
      residents of 42 US OG programs. RESULTS: A total of 21 program directors and 35
      graduating residents responded. There was no significant difference between the
      number of hysterectomies residents and program directors thought should be
      performed. Only 38.1% of program directors and 27.8% of residents reported
      graduating residents as being "completely prepared" to perform a vaginal
      hysterectomy compared with 76.2% and 58.3% for abdominal, 28.6% and 22.2% for
      laparoscopic, and 0% and 2.8% for robotic hysterectomies. Only 12.1% of
      graduating residents and 17.7% of program directors reported residents sitting at
      the console "often" or "always" during robotic surgery. Only 34.3% of residents
      plan to perform robotic hysterectomy after graduation. Both residents (77.2%) and
      program directors (71.5%) reported that robotic surgery is having a negative
      impact on residents' training nationally. CONCLUSIONS: : Graduating residents
      report adequate numbers of vaginal and abdominal hysterectomies. Both residents
      and program directors report that graduating residents are not prepared to
      perform all types of hysterectomies. Both residents and program directors express
      concern that robotic surgery is negatively impacting surgical training. Further
      efforts are needed to ensure that residents are graduating with surgical
      proficiency in these basic gynecologic procedures.

PMID- 22453101
TI  - Nimesulide inhibited the growth of hypopharyngeal carcinoma cells via suppressing
      Survivin expression.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy of
      Nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, on the growth of
      hypopharyngeal carcinoma cells (FaDu) in vitro, and investigate its potential
      mechanism. METHODS: After FaDu cells were treated with graded concentrations of
      Nimesulide for divergent time, sensitivity of cells to drug treatment was
      analyzed by MTT assay. Morphological changes of FaDu cells in the presence of
      Nimesulide were observed by acridine orange cytochemistry staining. Proliferating
      cells were detected using the 5-Bromo-2'-deoxy-uridine (BrdU) incorporation
      assay. Following cells were subjected to Nimesulide (500 MUmol/l) for 6 h, 12 h
      and 24 h, the percentage of apoptosis was examined by flow cytometry. We detected
      COX-2 and Survivin expression change by RT-PCR and Western blot, and analyzed the
      correlation of them with the growth of FaDu cells. Additionally, we also analyzed
      Caspase-3, Bcl-2 and Bax expressions as markers to investigate the related
      pathway of Nimesulide-indued apoptosis. RESULTS: Compared with the control group,
      the viabilities rates were decreased by Nimesulide in time- and dose-dependent
      manners, typical morphological changes of apoptotic cells were observed in the
      Nimesulide-treatment groups, Nimesulide could suppress the proliferation of FaDu
      cells significantly. The percentage of apoptosis in FaDu cells were markedly
      increased after Nimesulide-treatment for 6 h, 12 h and 24 h. Nimesulide down
      regulated the Survivin and COX-2 expressions at mRNA and protein levels in FaDu
      cells. Additional analyses indicated that Bcl-2 expression was significantly
      decreased and the expressions of Caspase-3 as well as Bax were increased at both
      mRNA and protein levels. CONCLUSIONS: Based on the induction of apoptosis and
      suppression of proliferation, Nimesulide could inhibit the growth of FaDu cells.
      Furthermore, the suppression of Survivin expression may play an important role in
      Nimesulide-induced growth inhibition. Nimesulide could act as an effective
      therapeutic agent for hypopharyngeal carcinoma therapy.

PMID- 22453100
TI  - Dual targeting strategies with bispecific antibodies.
AB  - Monoclonal antibodies are widely used for the treatment of cancer, inflammatory
      and infectious diseases and other disorders. Most of the marketed antibodies are
      monospecific and therefore capable of interacting and interfering with a single
      target. However, complex diseases are often multifactorial in nature, and involve
      redundant or synergistic action of disease mediators or upregulation of different
      receptors, including crosstalk between their signaling networks. Consequently,
      blockade of multiple, different pathological factors and pathways may result in
      improved therapeutic efficacy. This result can be achieved by combining different
      drugs, or use of the dual targeting strategies applying bispecific antibodies
      that have emerged as an alternative to combination therapy. This review discusses
      the various dual targeting strategies for which bispecific antibodies have been
      developed and provides an overview of the established bispecific antibody
      formats. 

PMID- 22453104
TI  - Commercial products for pelvic repair.
AB  - OBJECTIVE: : This article lists and describes the commercial products available
      for pelvic repair surgery as of summer 2011, tabulated by manufacturer as well as
      the type of application. METHODS: : Print advertisements in gynecologic and
      urogynecologic journals were searched, and products were tabulated. Web sites for
      the products were then located and summarized. Manufacturers were contacted to
      provide information not available on the Internet, particularly the physical
      characteristics of the meshes. Because of the plethora of products available
      (approximately 100 at this time), it is frequently difficult for the surgeon to
      identify the alternative products for a particular application or to identify the
      characteristics of a product used for a patient operated on elsewhere.
      CONCLUSIONS: : This article presents and describes a list of mesh products
      available for treatment of pelvic prolapse and stress urinary incontinence,
      described and arranged both by manufacturer and by application.

PMID- 22453105
TI  - Neuromuscular characterization of the urethra in continent women.
AB  - OBJECTIVES: : The study's objective was to describe quantitative urethral
      function parameters in a racially diverse group of continent women. MATERIALS AND
      METHODS: : After institutional review board approval, we recruited women without
      urinary incontinence from the community. To be considered continent, participants
      answered "never" to the first 6 questions on the stress subscale of the Medical,
      Epidemiologic, and Social Aspects of Aging urinary incontinence questionnaire.
      Participants all underwent quantitative concentric urethral electromyography
      (EMG) and urodynamic testing. RESULTS: : Thirty-one women with a mean (SD) age of
      39 (14) years underwent EMG and urodynamic testing. The cohort was racially
      diverse with 13 (43%) white women, 13 (43%) African American women, and 4 (14%)
      Hispanic women. Body mass index (P = 0.12, 0.06), age (P = 0.40, 0.64), and
      vaginal parity (P = 0.53, 0.76) did not differ by race or ethnicity. We did not
      detect differences in any EMG parameter by race, ethnicity, or vaginally parity.
      A mean (range) of 30 (10-55) motor unit action potential (MUP) analyses was
      identified and analyzed in multiple MUP analysis, and 14 (8-21) were identified
      and analyzed in interference pattern (IP) analysis. On average, 37% (20%) (mean
      [SD]) MUPs were polyphasic.Age significantly correlated with several measures of
      urethral sphincter function. Increasing age was inversely correlated with IP
      turns (r = -0.57, P = 0.001), IP amplitude (r = -0.43, P = 0.02), IP turns
      amplitude ratio (r = -0.54, P = 0.003), and maximum urethral closure pressures (r
      = -0.41, P = 0.04). Similarly, maximum urethral closure pressures correlated with
      IP amplitude (r = 0.38, P = 0.04). CONCLUSIONS: : These urethral neuromuscular
      function data on the largest cohort of continent women fully characterized with
      quantitative urethral EMG demonstrate significant neuropathic MUP changes with
      advancing age.

PMID- 22453106
TI  - Patient expectations did not predict outcome of drug and behavioral treatment of
      urgency urinary incontinence.
AB  - OBJECTIVES: : This study aimed to determine whether expectations of treatment
      outcomes in women participating in a drug and behavioral treatment trial for urge
      urinary incontinence are related to patient factors, demographics, health-related
      locus of control, and treatment outcomes. METHODS: : Baseline assessments
      included expectations (improvement in bladder condition, time to improvement in
      bladder condition, and duration of improvement) and the Medical Health Locus of
      Control (MHLC) scale. Outcomes were measured by the Patient Global Impression of
      Improvement scale (PGI-I) at the end of active treatment (10 weeks) and 8 months
      after trial start. RESULTS: : At baseline among 173 subjects, 114 (66%) believed
      their incontinence would get "very much better," 94 (55%) expected improvement by
      1 month, and 111 (66%) expected improvement would last for the rest of their
      lives. There were no significant associations between baseline expectations or
      MHLC with the Patient Global Impression of Improvement scale at 10 weeks or 8
      months. CONCLUSIONS: : Expectations of treatment outcome and MHLC did not predict
      eventual patient-reported treatment outcome in this sample of women with urge
      predominant urinary incontinence participating in a trial of drug and behavioral
      therapy.

PMID- 22453107
TI  - Resident training in female sexual dysfunction: a comparison of urology and
      obstetrics and gynecology programs.
AB  - OBJECTIVE: : The study's objective was to develop a tool that would characterize
      and compare resident training in female sexual dysfunction (FSD). METHODS: : A
      questionnaire was designed. Internet distribution targeted program directors of
      accredited urology and obstetrics and gynecology programs (N = 351). RESULTS: :
      Sixty-nine percent of programs did not have a standard protocol for working up
      patients with FSD, and 51% "rarely or never" have a faculty member with special
      training. Most (79%) agreed that resident training needed improvement. Barriers
      included lack of expert faculty, time, and resources. Obstetrics and gynecology
      program directors were more likely to agree with national training guidelines
      that promote FSD and more often encouraged residents to screen for FSD (63% vs
      24%). CONCLUSIONS: : Obstetrics and gynecology programs advocate FSD training
      more so than urology; however, both acknowledge its importance and the need for
      educational development.

PMID- 22453108
TI  - Improving resident screening and workup of urinary incontinence in an OB/GYN
      residency program: a randomized controlled study.
AB  - OBJECTIVES: : With an aging US population, an increased prevalence of urinary
      incontinence, rising health care costs, and a disease that remains largely
      unidentified, there is an immediate need to train physicians to screen for and
      treat incontinence. We aim to evaluate resident physician screening of urinary
      incontinence with a chart-based review. METHODS: : This study entailed 2 parts: a
      retrospective chart review (part 1) and a prospective randomized trial (part 2).
      Charts of 200 patients were retrospectively evaluated for documentation of
      bladder symptoms and incontinence for part 1. In part 2, patients' charts were
      prospectively randomized to receive a chart-alert sticker ("Do you leak urine?")
      that reminded resident physicians to ask about urinary incontinence in their
      general gynecology clinics. The primary outcome was documentation of urinary
      incontinence. Secondary outcomes were initiation of workup, diagnoses made, and
      treatment plans. Overall, 200 charts were needed for the prospective study to
      provide 80% power. RESULTS: : Residents documented any type of bladder symptom
      (incontinence, urgency, frequency, dysuria, nocturia) in 32 (16.3%) of 196 charts
      in part 1 and 45 (23.7%) of the 190 randomized charts in part 2 (P = 0.154). In
      the prospective study, 88 included charts were randomized to receive the "Do you
      leak urine?" chart-alert sticker and 102 were randomized to no sticker. Residents
      documented that they asked about incontinence in 30 (34.1%) of the charts with
      stickers versus 4 (3.9%) of the charts without (P = 0.001). CONCLUSIONS: Overall,
      the rate that resident physicians inquired about incontinence increased with the
      alert-sticker from 4% to 34%. Directed education will likely further this
      improvement.

PMID- 22453109
TI  - Validation of a visual analog scale form of the pelvic organ prolapse/urinary
      incontinence sexual function questionnaire 12.
AB  - OBJECTIVE: : This study aimed to validate a visual analog scale (VAS) form of the
      Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12).
      METHODS: : This was a planned secondary analysis of a vaginal anatomy and sexual
      function study. All women undergoing vaginal reconstruction between October 2008
      and December 2009 were asked to participate. We planned for an analysis of 30
      women for this validation. Preoperatively, sexually active participants completed
      a questionnaire containing a PISQ-12 in Likert (0-4) and VAS (0-10) format.
      Within 30 days, participants completed a PISQ-12 in VAS form only for evaluation
      of test-retest reliability. At 6 months after surgery, participants completed the
      PISQ-12 in both the Likert and VAS forms. For each item on the PISQ-12, the
      Spearman rank correlation coefficient was used to estimate the correlation
      between the Likert and VAS formats using the responses from the same assessment
      period (before or after surgery). The intraclass correlation coefficient was
      estimated to assess the test-retest agreement. RESULTS: : A total of 43 women
      completed the preoperative questionnaire, 25 completed the retest, and 37
      completed the postoperative questionnaire. When PISQ-12 scores were compared
      between the Likert and VAS forms, correlation values were 0.88 preoperatively and
      0.91 postoperatively. Test-retest reliability was high with an intraclass
      correlation coefficient of 0.87. Most women preferred the Likert version (71.4%
      preoperatively and 55.0% postoperatively). CONCLUSIONS: : The VAS form of the
      PISQ-12 is both reliable and reproducible and avoids the limitations of the
      Likert scale.

PMID- 22453110
TI  - Patient characteristics associated with a successful pessary fitting.
AB  - OBJECTIVE: : The objective of the study was to assess if patient characteristics,
      including Pelvic Organ Prolapse Quantification measurements, are predictive of
      successful pessary fitting in women with pelvic organ prolapse (POP) and/or
      incontinence. METHODS: : This was a retrospective chart review of patients who
      underwent a pessary fitting for POP and/or incontinence. Multiple demographic
      parameters, pessary fitting data, and Pelvic Organ Prolapse Quantification
      measurements were examined. RESULTS: : Complete data were available on 158
      patients, and 59% were successfully fit. Shorter total vaginal length (TVL), less
      than 8 cm, was associated with an unsuccessful pessary fitting (odds ratio [OR],
      0.1; 95% confidence interval [CI], 0.02-0.46). A genital hiatus (GH)/TVL ratio of
      less than 0.9 was predictive of successful fitting (OR, 12.5; 95% CI, 1.5-102).
      Patients with a prior hysterectomy were more likely to have an unsuccessful
      pessary fitting (OR, 0.41; 95% CI, 0.22-0.8). The GH/TVL ratio and TVL were
      predictors only in patients with a previous hysterectomy. CONCLUSIONS: : Patients
      with a previous hysterectomy and a TVL of less than 8 cm or a GH/TVL ratio of 0.9
      or greater can be counseled that successful pessary fitting is unlikely.

PMID- 22453111
TI  - Repeat intradetrusor injections of onabotulinum toxin a for refractory idiopathic
      overactive bladder patients: a single-center experience.
AB  - OBJECTIVES: : The objective of the study was to evaluate the safety and efficacy
      of repeat intradetrusor onabotulinum toxin A injection in patients with
      idiopathic overactive bladder refractory to anticholinergic medications.
      Furthermore, 2 doses, 100 and 150 U, were compared. METHODS: : We prospectively
      enrolled 60 patients in our investigator-initiated, single-center randomized
      trial. Thirty patients were randomized to each dosage arm. Total study duration
      was 3 years. Patients were eligible to receive 6 onabotulinum toxin A injections.
      Subjects completed a 3-day voiding diary and Urogenital Distress Inventory 6 (UDI
      6) questionnaire and graded their quality of life on a visual analog scale (VAS)
      before study enrollment and at week 6 after every injection. The outcome was
      based on the amount of improvement noted on the UDI-6 and VAS scores at 6 weeks
      post every injection as compared with study enrollment. RESULTS: : There were 9
      men and 51 women. The mean UDI-6 and VAS scores improved significantly (P =
      0.0001) at week 6 after initial onabotulinum toxin A injection, and no change was
      seen when comparing repeat injections; 20% and 10% of the patients randomized to
      150 and 100 U required performing clean intermittent catheterization,
      respectively. The mean UDI-6 scores after repeat onabotulinum toxin A injections
      did not differ significantly between 100 and 150 U. CONCLUSIONS: : Repeat
      injections of onabotulinum toxin A are capable of significantly improving UDI-6
      scores and quality of life in refractory patients with idiopathic overactive
      bladder. There was no evidence of decreased efficacy after repeat injections.
      Lower clean intermittent catheterization rates were noted in patients randomized
      to 100 U as compared with 150 U. Both doses, 100 and 150 U, were equally
      efficacious.

PMID- 22453112
TI  - Delayed presentation of an enterocutaneous fistula after tension-free vaginal
      tape sling.
AB  - BACKGROUND: : Bowel injury is a rare but serious complication associated with
      tension-free vaginal tape (TVT) sling procedures. CASE: : A 50-year-old woman
      with a previous history of pelvic surgery underwent TVT for stress urinary
      incontinence. Surgery and the immediate postoperative period were unremarkable;
      however, she returned 5 months later with bloody, purulent discharge from a
      suprapubic exit site. This was unresponsive to antibiotic therapy, and when the
      patient returned with abdominal pain and fever, a computed tomographic scan
      showed an enterocutaneous fistula. At the time of exploratory laparotomy, the
      mesh was noted to have perforated the small bowel and led to a sinus tract that
      communicated with the skin. CONCLUSIONS: : Bowel perforation is a recognized, but
      rare, complication of TVT. This case highlights the need for a high index of
      suspicion for bowel injury after TVT maintained beyond the more commonly
      described peritonitis or obstructive symptoms presenting in the immediate
      perioperative period.

PMID- 22453113
TI  - Severe acidosis during laparoscopic repair of pelvic organ prolapse and
      incontinence.
AB  - The creation and maintenance of a carbon dioxide pneumoperitoneum to allow a
      laparoscopic approach to surgery for pelvic organ prolapse has been associated
      with hypercapnea and respiratory acidosis. We present a case report of a 68-year
      old patient who developed severe acidosis during a robotic-assisted laparoscopic
      sacrocolpopexy and discuss a practical approach to surgical and anesthetic
      decision making.

PMID- 22453114
TI  - The effects of multi-domain versus single-domain cognitive training in non
      demented older people: a randomized controlled trial.
AB  - BACKGROUND: Whether healthy older people can benefit from cognitive training
      (CogTr) remains controversial. This study explored the benefits of CogTr in
      community dwelling, healthy, older adults and compared the effects of single
      domain with multi-domain CogTr interventions. METHODS: A randomized, controlled,
      3-month trial of CogTr with double-blind assessments at baseline and immediate, 6
      month and 12-month follow-up after training completion was conducted. A total of
      270 healthy Chinese older people, 65 to 75 years old, were recruited from the
      Ganquan-area community in Shanghai. Participants were randomly assigned to three
      groups: multi-domain CogTr, single-domain CogTr, and a wait-list control group.
      Twenty-four sessions of CogTr were administrated to the intervention groups over
      a three-month period. Six months later, three booster training sessions were
      offered to 60% of the initial training participants. The Repeatable Battery for
      the Assessment of Neuropsychological Status (RBANS, Form A), the Color Word
      Stroop test (CWST), the Visual Reasoning test and the Trail Making test (TMT)
      were used to assess cognitive function. RESULTS: Multi-domain CogTr produced
      statistically significant training effects on RBANS, visual reasoning, and
      immediate and delayed memory, while single-domain CogTr showed training effects
      on RBANS, visual reasoning, word interference, and visuospatial/constructional
      score (all P < 0.05). At the 12-month posttest, the multi-domain CogTr showed
      training effects on RBANS, delayed memory and visual reasoning, while single
      domain CogTr only showed effects on word interference. Booster training resulted
      in effects on RBANS, visual reasoning, time of trail making test, and
      visuospatial/constructional index score. CONCLUSIONS: Cognitive training can
      improve memory, visual reasoning, visuospatial construction, attention and
      neuropsychological status in community-living older people and can help maintain
      their functioning over time. Multi-domain CogTr enhanced memory proficiency,
      while single-domain CogTr augmented visuospatial/constructional and attention
      abilities. Multi-domain CogTr had more advantages in training effect maintenance.
      CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry. REGISTRATION
      NUMBER: ChiCTR-TRC-09000732.

PMID- 22453115
TI  - Sonographic evaluation of sciatic nerves in patients with unilateral sciatica.
AB  - OBJECTIVES: To evaluate the sciatic nerves of patients with unilateral sciatica
      by using an ultrasound, and to determine whether ultrasonographic findings were
      related to clinical and electrophysiologic parameters. DESIGN: Cross-sectional
      study. SETTING: Physical medicine and rehabilitation departments of a university
      hospital and a rehabilitation hospital. PARTICIPANTS: Consecutive patients (N=30;
      10 men, 20 women) with complaints of low back pain and unilateral sciatica of
      more than 1 month of duration were enrolled. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: All patients underwent a substantial clinical assessment, and
      they were also evaluated by electromyogram and magnetic resonance imaging. Pain
      was evaluated by a visual analog scale and the Leeds Assessment of Neuropathic
      Symptoms and Signs (LANSS) Scale. A linear array probe (7.5-12MHz) was used to
      scan sciatic nerves bilaterally in the prone position. Sciatic nerve diameters
      thickness (short axis) and width (long axis)-and cross-sectional areas were
      measured bilaterally at the same levels, proximal to the bifurcation and
      midthigh. The values pertaining to the unaffected limbs were taken as controls.
      RESULTS: When compared with the unaffected sides, mean values for sciatic nerve
      measurements-long axis at bifurcation level (P=.017) and cross-sectional area at
      midthigh level (P=.005)-were significantly larger on the affected sides. Swelling
      ratios negatively correlated with symptom duration (r=-.394, P=.038) and LANSS
      scores (r=-.451, P=.016) at only midthigh level. CONCLUSIONS: Sciatic nerves seem
      to be enlarged on the side of sciatica in patients with low back pain. Our
      preliminary results may provide insight into better understanding the lower limb
      radiating pain in this group of patients.

PMID- 22453116
TI  - Multifunctional modified silver nanoparticles as ion and pH sensors in aqueous
      solution.
AB  - Silver nanoparticles capped with mercaptoacetic acid and 2-aminoethanethiol short
      chain alkanethiols were prepared by a one-step method in aqueous solution for
      monitoring pH and a range of heavy metal ions. The mode of transduction is
      optical, based on the change in aggregation of the nanoparticles in solution.
      Because of the different ionic interactions between the modified nanoparticles,
      these nanoparticle sensors can rapidly detect Pb(2+), Cu(2+) and Fe(2+), with
      detection limits as low as 1 * 10(-5) M, 5 * 10(-7) M and 5 * 10(-5) M
      respectively, as well as having the ability to detect Cu(2+) ions from Pb(2+) and
      Fe(2+). Furthermore, the same functionalised nanoparticles are also sensitive to
      pH; exhibiting a good linear dynamic response between pH 1 and 10.

PMID- 22453117
TI  - Fossil fungi with suggested affinities to the Endogonaceae from the Middle
      Triassic of Antarctica.
AB  - Documented fossil evidence of zygomycetous fungi is rare. A conspicuous fungal
      fossil, Jimwhitea circumtecta gen. et sp. nov., occurs in permineralized peat
      from the Middle Triassic of Antarctica. The fossil is interpreted as a mantled
      zygosporangium that buds from a macrogametangium subtended by a sac-like
      macrosuspensor. The macrogametangium is united at its tip with a microgametangium
      which is subtended by a micro-suspensor. This configuration is strikingly similar
      to the zygosporangium-gametangia complexes seen in certain modern Endogonaceae.
      Co-occurring with J. circumtecta are isolated propagules closely resembling the
      zygosporangium of J. circumtecta and a portion of a sporocarp containing
      zygosporangia embedded in a gleba. Several of the sporangia are borne on ovoid or
      elongate structures, which we interpret as gametangia. These fossils offer an
      exceptionally detailed view of the morphology and reproductive biology of early
      Mesozoic zygomycetes.

PMID- 22453118
TI  - Three new genera representing novel lineages of Sordariomycetidae
      (Sordariomycetes, Ascomycota) from tropical freshwater habitats in Costa Rica.
AB  - Three new genera are established in the Sordariomycetidae based on morphological
      and molecular data (SSU and LSU nrDNA) to accommodate five ascomycete species
      collected from submerged woody debris in freshwater habitats from Costa Rica. The
      genus Bullimyces contains three new species, B. communis, B. costaricensis and B.
      aurisporus. Bullimyces is characterized by globose to subglobose, membranous,
      black, ostiolate ascomata; deliquescent, hyaline, globose cells that fill the
      center of the centrum; unitunicate asci that deliquesce early in some species;
      and septate, thick-walled ascospores with or without gelatinous sheaths or
      appendages. Bullimyces species form a well supported clade with 100% bootstrap
      support, but the position of the genus in the Sordariomycetidae remains unclear.
      The second genus, Riomyces, is represented by a single species, R. rotundus.
      Riomyces is characterized by globose to subglobose, membranous, black, ostiolate
      ascomata, unitunicate, cylindrical asci, hyaline, globose cells that fill the
      hamathecium and septate, thick-walled ascospores with a gelatinous sheath.
      Although Riomyces is morphologically similar to Bullimyces, the two genera did
      not group together with support in any analysis. The third genus, Hydromelitis,
      is represented by a single species, H. pulchella. Hydromelitis is characterized
      by pyriform, membranous, black, ostiolate ascomata, unitunicate asci lacking an
      apical structure, simple, thin-walled, septate paraphyses and hyaline to golden
      yellow, multiseptate, thick-walled ascospores with a gelatinous sheath.
      Bullimyces, Riomyces and Hydromelitis were nested within an unsupported clade
      consisting of members of the Ophiostomatales, Magnaporthales and freshwater
      Annulatacaceae sensu lato and sensu stricto.

PMID- 22453120
TI  - Cytological karyotyping and characterization of a 410 kb minichromosome in
      Nectria haematococca MPI.
AB  - Karyotypes of the cucurbit pathogen Nectria haematococca MPI (anamorph Fusarium
      solani f. sp. cucurbitae race 1) was studied using the two standard strains
      ATCC18098 and ATCC18099. Complete separation of all chromosomes was difficult
      with pulsed field gel electrophoresis due to both the large size and co-migration
      of chromosomes. In contrast, cytological karyotyping was done successfully with
      fluorescence microscopy combined with the germ tube burst method for sample
      preparation to visualize mitotic metaphase chromosomes. For each strain the basic
      chromosome number (CN) was nine, which revises previous chromosome estimates of n
      = 4. Chromosomes were morphologically characterized by their sizes, intensely
      fluorescing segments, and protrusion of rDNA. In addition to the basic chromosome
      complement, ATCC18098 had a mini-chromosome of ~410 kb present as a single copy
      in somatic nuclei. Chromosome fluorescence in situ hybridization indicated that
      this mini-chromosome is not a derivative from the other chromosomes in the
      genome. In addition, crossing experiments suggested that it was transmitted in a
      Mendelian manner to the ascospore progeny.

PMID- 22453119
TI  - Phylogenetic placement of the ectomycorrhizal genus Cenococcum in Gloniaceae
      (Dothideomycetes).
AB  - Cenococcum is a genus of ectomycorrhizal Ascomycota that has a broad host range
      and geographic distribution. It is not known to produce either meiotic or mitotic
      spores and is known to exist only in the form of hyphae, sclerotia and host
      colonized ectomycorrhizal root tips. Due to its lack of sexual and asexual spores
      and reproductive structures, it has proven difficult to incorporate into
      traditional classification within Ascomycota. Molecular phylogenetic studies of
      ribosomal RNA placed Cenococcum in Dothideomycetes, but the definitive
      identification of closely related taxa remained elusive. Here we report a
      phylogenetic analysis of five nuclear loci (SSU, LSU, TEF1, RPB1, RPB2) of
      Dothideomycetes that placed Cenococcum as a close relative of the genus Glonium
      of Gloniaceae (Pleosporomycetidae incertae sedis) with strong statistical
      support. Glonium is a genus of saprobic Dothideomycetes that produces darkly
      pigmented, carbonaceous, hysteriate apothecia and is not known to be biotrophic.
      Evolution of ectomycorhizae, Cenococcum and Dothideomycetes is discussed.

PMID- 22453121
TI  - Basidiome formation of an edible wild, putatively ectomycorrhizal fungus,
      Phlebopus portentosus without host plant.
AB  - Phlebopus portentosus is a popular wild edible ectomycorrhizal fungus in northern
      Thailand. In general ectomycorrhizal fungi produce basidiomes when associated
      with a host plant. In this paper mycelium growth and basidiome production of P.
      portentosus were examined in pure culture both in vitro and in pot-culture
      experiments. Five mycelial strains of P. portentosus were isolated from
      basidiomes and used in the experiments. The mycelia grew fastest on sorghum
      grains supplemented with fungal-host solution. The mycelia produced sclerotia
      like structures after 3 wk incubation in darkness at 30 C. All strains of P.
      portentosus had the ability to form primordia. The primordia were formed under
      lowered temperature, high humidity and a 12 h photo-period. They developed to
      mature basidiomes after 8-12 d in in vitro. In the pot-culture primordia were
      found after 28-35 d incubation in the greenhouse and mature basidiomes released
      basidiospores within 6-8 d. Basidiospores were germinated on fungal-host medium
      and formed mycelial colonies. This fungus showed an ability to produce basidiomes
      even 2 y after the original isolation from tissues. This research provides
      valuable information concerning the techniques and protocols for the large scale
      commercial production of P. portentosus basidiomes in the absence of a host
      plant.

PMID- 22453123
TI  - Chemotypic and genotypic diversity in the ergot alkaloid pathway of Aspergillus
      fumigatus.
AB  - Aspergillus fumigatus is an opportunistic human pathogen that synthesizes a group
      of mycotoxins via a branch of the ergot alkaloid pathway. This fungus is globally
      distributed, and genetic data indicate that isolates recombine freely over that
      range; however, previous work on ergot alkaloids has focused on a limited number
      of isolates. We hypothesized that A. fumigatus harbors variation in the chemotype
      of ergot alkaloids and genotype of the ergot alkaloid gene cluster. Analysis of
      13 isolates by high performance liquid chromatography revealed four distinct
      ergot alkaloid profiles or chemotypes. Five isolates completed the A. fumigatus
      branch of the ergot alkaloid pathway to fumigaclavine C. Six independent isolates
      accumulated fumigaclavine A, the pathway intermediate immediately before
      fumigaclavine C. One isolate accumulated only the early pathway intermediates
      chanoclavine-i and chanocla-vine-i aldehyde, and one isolate lacked ergot
      alkaloids altogether. A genetic basis for each of the observed chemotypes was
      obtained either by PCR analysis of the ergot alkaloid gene cluster or through
      sequencing of easL, the gene encoding the prenyl transferase that reverse
      prenylates fumigaclavine A to fumigaclavine C. Isolates also exhibited
      differences in pigmentation and sporulation. The ergot alkaloid chemotypes were
      widely distributed geographically and among substrate of origin.

PMID- 22453122
TI  - Blue pigment in Hypocrea caerulescens sp. nov. and two additional new species in
      sect. Trichoderma.
AB  - Three new species of Hypocrea/Trichoderma sect. Trichoderma (Hypocreaceae,
      Hypocreales, Ascomycota, Fungi) are described from recent collections in southern
      Europe and the Canary Islands. They have been characterized by morphological and
      molecular methods, including microscopic examination of the teleomorph in thin
      sections, the anamorph, growth rate experiments and phylogenetic analyses based
      on a part of the translation elongation factor 1-alpha encoding gene (tef1)
      containing the two last introns and a part of the rpb2 gene, encoding the second
      largest RNA polymerase subunit. Analyses involving tef1 did not unequivocally
      resolve the sister clade relationship of Hypocrea caerulescens relative to the
      Koningii and Viride clades, while analyses based on rpb2 clearly suggest a close
      relationship with the former, although the phenotype of H. caerulescens is
      similar to H. viridescens, particularly by its warted conidia and a coconut-like
      odor in CMD culture. Hypocrea hispanica and T. samuelsii however are clearly
      related to the Viride clade by both phylogenetic markers, despite their
      morphological similarity to H. koningii and its relatives. An apparently specific
      blue pigment is formed in CMD cultures by Hypocrea caerulescens but could not be
      obtained by extraction with organic solvents.

PMID- 22453124
TI  - Effects of microinjections of Group II metabotropic glutamate agents into the
      amygdala on sleep.
AB  - Systemic administration of the Group II metabotropic glutamate (mGlu) receptor
      agonist, LY379268 (LY37), dose-dependently suppresses rapid eye movement sleep
      (REM) whereas systemic administration of the mGlu II receptor antagonist,
      LY341495 (LY34), increases arousal. Group II mGlu receptors are highly expressed
      in the amygdala, a brain region involved in the regulation of sleep and arousal.
      To determine whether the amygdala is involved in mediating the effects of Group
      II mGlu agents on sleep, we microinjected LY37 and LY34 into the basal amygdala
      (BA) and the central nucleus of the amygdala (CNA) and recorded sleep and
      wakefulness. Wistar rats were implanted with electrodes for recording sleep and
      with bilateral cannulae aimed into BA for drug administration. Different groups
      of rats received bilateral microinjections of LY37 into BA at two dosage ranges
      (3.2 mM, 5.3 mM or 10.7 mM or 0.1 nM, 2.0 nM or 10.0 nM) or one dosage range of
      LY34 (1.0 nM, 30.0 nM or 60.0 nM). Microinjections into CNA were conducted at one
      dosage range for LY37 (0.1 nM, 2.0 nM or 10.0 nM) and for LY34 (1.0 nM, 30.0 nM
      or 60.0 nM). All drugs or vehicle alone were administered in a counterbalanced
      order at 5-day intervals. Following microinjection, sleep was recorded for 20 h.
      Microinjection of LY37 into BA at both nM and mM concentrations significantly
      decreased REM without significantly altering NREM, total sleep or wakefulness.
      The high dosage of LY34 in BA significantly suppressed NREM and total sleep.
      Microinjections of LY37 or LY34 into CNA had no significant impact on sleep. We
      suggest that Group II mGlu receptors may influence specific cells in BA that
      control descending output (via the CNA or bed nucleus of the stria terminalis)
      that in turn regulates pontine REM generator regions.

PMID- 22453125
TI  - MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like
      SP cells in colorectal cancer.
AB  - BACKGROUND: Side population (SP) cells and their relationship to stem cell-like
      properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs
      (miRNAs) have attracted much attention but their roles in the maintenance of SP
      phenotype remain unclear. METHODS: The SPs from CRC cell lines and primary cell
      cultures were analysed for stem cell-like properties. MiRNA microarray analysis
      identified miR-328 as a potential stemness miRNA of SP phenotype. The level of
      miR-328 expression in clinical samples and its correlation with SP fraction were
      determined. Gain-of-function and loss-of-function studies were performed to
      examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics
      prediction and experimental validation were used to identify miR-328 target
      genes. RESULTS: The SP cells sorted from CRC possess cancer stem cell (CSC)-like
      properties, including self-renewal, differentiation, resistance to chemotherapy,
      invasive and strong tumour formation ability. MiR-328 expression was
      significantly reduced in SP cells compared with Non-SP cells (P<0.05). Moreover,
      miR-328 expression was downregulated in CRC (n=33, P<0.05) and low miR-328
      expression tend to correlate with high SP fraction (n=15, r=0.6559, P<0.05,
      Pearson's correlation). Functional studies indicated that miR-328 expression
      affects the number of SP cells. In addition, miR-328 overexpression reversed drug
      resistance and inhibited cell invasion of SP cells. Furthermore, luciferase
      reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and
      affects the levels of mRNA and protein expression in SP cells. CONCLUSION: These
      findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an
      important role in maintaining cancer stem-like SP phenotype that may be a
      potential target for effective CRC therapy.

PMID- 22453126
TI  - Increased risk of laryngeal and pharyngeal cancer after gastrectomy for ulcer
      disease in a population-based cohort study.
AB  - BACKGROUND: Gastrectomy has been indicated as a risk factor for laryngeal cancer,
      and possibly also for pharyngeal cancer, but few studies are available. The
      postulated mechanism is increased bile reflux following gastrectomy. METHODS:
      This was a population-based cohort study of patients who underwent gastrectomy
      for peptic ulcer disease between 1964 and 2008 in Sweden. Follow-up data for
      cancer was obtained from the Swedish Cancer Register. Relative risk was
      calculated as standardised incidence ratios (SIRs) with 95% confidence intervals
      (CIs). RESULTS: The gastrectomy cohort comprises 19 767 patients, contributing
      348 231 person-years at risk. The observed number of patients with laryngeal
      (n=56) and pharyngeal cancer (n=28) was two-fold higher than the expected (SIR:
      2.0, 95% CI: 1.5-2.6 and SIR: 2.4, 95% CI: 1.6-3.5, respectively). After
      exclusion of 5536 cohort members with tobacco- or alcohol-related disease, the
      point SIRs remained increased (SIR: 1.6, 95% CI: 1.1-2.2 and SIR: 1.7, 95% CI:
      0.9-2.8, respectively). The SIRs of laryngeal and pharyngeal cancer increased
      with time after gastrectomy (P for trend <0.0001), and were particularly
      increased ?30 years after gastrectomy (SIR: 4.8, 95% CI: 2.1-9.5 and SIR: 10.2,
      95% CI: 3.7-22.3, respectively). CONCLUSION: Gastrectomy for peptic ulcer disease
      might entail a long-term increased risk of laryngeal and pharyngeal cancer.

PMID- 22453127
TI  - Occupational risk factors have to be considered in the definition of high-risk
      lung cancer populations.
AB  - BACKGROUND: The aim of this study was to compute attributable fractions (AF) to
      occupational factors in an area in North-Eastern France with high lung cancer
      rates and a past of mining and steel industry. METHODS: A population-based case
      control study among males aged 40-79 was conducted, including confirmed primary
      lung cancer cases from all hospitals of the study region. Controls were
      stratified by broad age-classes, district and socioeconomic classes. Detailed
      occupational and personal risk factors were obtained in face-to-face interviews.
      Cumulative occupational exposure indices were obtained from the questionnaires.
      Attributable fractions were computed from multiple unconditional logistic
      regression models. RESULTS: A total of 246 cases and 531 controls were included.
      The odds ratios (ORs) adjusted on cumulative smoking and family history of lung
      cancer increased significantly with the cumulative exposure indices to asbestos,
      polycyclic aromatic hydrocarbons and crystalline silica, and with exposure to
      diesel motor exhaust. The AF for occupational factors exceeded 50%, the most
      important contributor being crystalline silica and asbestos. CONCLUSION: These
      AFs are higher than most published figures. This can be because of the highly
      industrialised area or methods for exposure assessments. Occupational factors are
      important risk factors and should not be forgotten when defining high-risk lung
      cancer populations.

PMID- 22453129
TI  - The Hypoactive Sexual Desire Disorder Registry to characterize the natural
      history and outcomes of women with hypoactive sexual desire disorder.

PMID- 22453130
TI  - Autonomic dysfunction:  a common mechanism for heart failure and hot flashes?

PMID- 22453131
TI  - Do high levels of physical activity favor favorable cardiovascular risk factors
      regardless of sleep?

PMID- 22453132
TI  - Aromatase inhibition to decrease background parenchymal enhancement: 
      premedication before magnetic resonance imaging?

PMID- 22453133
TI  - Assessment of liver fibrosis and associated risk factors in HIV-infected
      individuals using transient elastography and serum biomarkers.
AB  - BACKGROUND: Liver fibrosis in human immunodeficiency virus (HIV)-infected
      individuals is mostly attributable to co-infection with hepatitis B or C. The
      impact of other risk factors, including prolonged exposure to combined
      antiretroviral therapy (cART) is poorly understood. Our aim was to determine the
      prevalence of liver fibrosis and associated risk factors in HIV-infected
      individuals based on non-invasive fibrosis assessment using transient
      elastography (TE) and serum biomarkers (Fibrotest [FT]). METHODS: In 202
      consecutive HIV-infected individuals (159 men; mean age 47 +/- 9 years; 35 with
      hepatitis-C-virus [HCV] co-infection), TE and FT were performed. Repeat TE
      examinations were conducted 1 and 2 years after study inclusion. RESULTS:
      Significant liver fibrosis was present in 16% and 29% of patients, respectively,
      when assessed by TE (>= 7.1 kPa) and FT (> 0.48). A combination of TE and FT
      predicted significant fibrosis in 8% of all patients (31% in HIV/HCV co-infected
      and 3% in HIV mono-infected individuals). Chronic ALT, AST and gamma-GT elevation
      was present in 29%, 20% and 51% of all cART-exposed patients and in 19%, 8% and
      45.5% of HIV mono-infected individuals. Overall, factors independently associated
      with significant fibrosis as assessed by TE (OR, 95% CI) were co-infection with
      HCV (7.29, 1.95-27.34), chronic AST (6.58, 1.30-33.25) and gamma-GT (5.17, 1.56
      17.08) elevation and time on dideoxynucleoside therapy (1.01, 1.00-1.02). In 68
      HIV mono-infected individuals who had repeat TE examinations, TE values did not
      differ significantly during a median follow-up time of 24 months (median intra
      patient changes at last TE examination relative to baseline: -0.2 kPa, p = 0.20).
      CONCLUSIONS: Chronic elevation of liver enzymes was observed in up to 45.5% of
      HIV mono-infected patients on cART. However, only a small subset had significant
      fibrosis as predicted by TE and FT. There was no evidence for fibrosis
      progression during follow-up TE examinations.

PMID- 22453134
TI  - Antiviral effects of Psidium guajava Linn. (guava) tea on the growth of clinical
      isolated H1N1 viruses: its role in viral hemagglutination and neuraminidase
      inhibition.
AB  - Rapid evolution of influenza RNA virus has resulted in limitation of vaccine
      effectiveness, increased emergence of drug-resistant viruses and occurrence of
      pandemics. A new effective antiviral is therefore needed for control of the
      highly mutative influenza virus. Teas prepared by the infusion method were tested
      for their anti-influenza activity against clinical influenza A (H1N1) isolates by
      a 19-h influenza growth inhibition assay with ST6Gal I-expressing MDCK cells (AX4
      cells) using fluorogenic quantification and chromogenic visualization. Guava tea
      markedly inhibited the growth of A/Narita/1/2009 (amantadine-resistant pandemic
      2009 strain) at an IC(50) of 0.05% and the growth of A/Yamaguchi/20/06 (sensitive
      strain) and A/Kitakyushu/10/06 (oseltamivir-resistant strain) at similar IC(50)
      values ranging from 0.24% to 0.42% in AX4 cells, being 3.4- to 5.4-fold more
      potent than green tea (IC(50) values: 0.27% for the 2009 pandemic strain and
      0.91% to 1.44% for the seasonal strains). In contrast to both teas, oseltamivir
      carboxylate (OC) demonstrated high potency against the growth of A/Narita/1/09
      (IC(50) of 3.83nM) and A/Yamaguchi/20/06 (IC(50) of 11.57nM) but not against that
      of A/Kitakyushu/10/06 bearing a His274-to-Tyr substitution (IC(50) of 15.97MUM).
      Immunofluorescence analysis under a confocal microscope indicated that both teas
      inhibited the most susceptible A/Narita/1/2009 virus at the initial stage of
      virus infection. This is consistent with results of direct inhibition assays
      showing that both teas inhibited viral hemagglutination at concentrations
      comparable to their growth inhibition concentrations but inhibited sialidase
      activity at about 8-times higher concentrations. Guava tea shows promise to be
      efficacious for control of epidemic and pandemic influenza viruses including
      oseltamivir-resistant strains, and its broad target blockage makes it less likely
      to lead to emergence of viral resistance.

PMID- 22453135
TI  - Long-term monitoring drug resistance by ultra-deep pyrosequencing in a chronic
      hepatitis B virus (HBV)-infected patient exposed to several unsuccessful therapy
      schemes.
AB  - The aim of this study was to analyze the spectrum and dynamics of low-prevalent
      HBV mutations in the reverse transcriptase (rt) and S antigen by ultra-deep
      pyrosequencing (UDPS). Samples were obtained from a chronically infected patient
      who was followed throughout a thirteen-year period. This technology enabled
      simultaneous analysis of 4084 clonally amplified fragments from the patient
      allowing detecting low prevalent (<1%) mutations during the follow-up. At
      baseline, HBV sequences were predominately wild-type. Under sequential HBV
      monotherapies including lamivudine, adefovir and entecavir, a high frequency of
      rtM204I mutation was detected initially as unique and then coexisting with
      rtM204V. Both mutations were statistically associated with rtA200V and rtV207I,
      respectively. Once the entecavir and tenofovir combined therapy was started,
      polymerase and consequently envelope gene mutations appeared at several positions
      at a higher frequency than before, including the entecavir resistance-associated
      mutation rtT184L.

PMID- 22453136
TI  - A novel mechanism of cocaine to enhance dopamine d2-like receptor mediated
      neurochemical and behavioral effects. An in vivo and in vitro study.
AB  - Recent in vitro results suggest that cocaine may exert direct and/or indirect
      allosteric enhancing actions at dopamine (DA) D(2) receptors (D(2)Rs). In the
      present paper we tested the hypothesis that cocaine in vivo can enhance the
      effects of the D(2)-likeR agonist quinpirole in rats by using microdialysis and
      pharmacological behavioral studies. Furthermore, in vitro D(2)-likeR binding
      characteristics and Galpha(i/o)-protein coupling, in the absence and in the
      presence of cocaine, have been investigated in rat striatal membranes. Intra
      nucleus accumbens perfusion of the D(2)-likeR agonist quinpirole (10 MUM) reduced
      local dialysate glutamate levels, whereas cocaine (10 and 100 nM) was
      ineffective. At a low concentration (100 nM), cocaine significantly enhanced
      quinpirole-induced reduction of accumbal extracellular glutamate levels. The
      behavioral experiments showed that cocaine (0.625 mg/kg), but not the DA uptake
      blocker GBR 12783 (1.25 mg/kg), enhanced quinpirole (1 mg/kg)-induced
      hyperlocomotion. Finally, cocaine (100 nM), but not GBR 12783 (200 nM), produced
      a small, but significant increase in the efficacy of DA to stimulate binding of
      GTPgammaS to striatal D(2)-likeRs, whereas the D(2)-likeR binding characteristics
      were unchanged in striatal membranes by cocaine in the nM range. The significant
      increase in the maximal response to DA-stimulated GTPgammaS binding to D(2)
      likeRs by 100 nM cocaine remained in the presence of GBR 12783. The observed
      cocaine-induced enhancement of the Galpha(i/o)-protein coupling of D(2)Rs may be
      in part because of allosteric direct and/or indirect enhancing effects of cocaine
      at these receptors. These novel actions of cocaine may have relevance for
      understanding the actions of cocaine upon accumbal DA, and/or glutamate
      transmission and thus its rewarding as well as relapsing effects.

PMID- 22453137
TI  - Novel use of a lipid-lowering fibrate medication to prevent nicotine reward and
      relapse: preclinical findings.
AB  - Experimental drugs that activate alpha-type peroxisome proliferator-activated
      receptors (PPARalpha) have recently been shown to reduce the rewarding effects of
      nicotine in animals, but these drugs have not been approved for human use. The
      fibrates are a class of PPARalpha-activating medications that are widely
      prescribed to improve lipid profiles and prevent cardiovascular disease, but
      these drugs have not been tested in animal models of nicotine reward. Here, we
      examine the effects of clofibrate, a representative of the fibrate class, on
      reward-related behavioral, electrophysiological, and neurochemical effects of
      nicotine in rats and squirrel monkeys. Clofibrate prevented the acquisition of
      nicotine-taking behavior in naive animals, substantially decreased nicotine
      taking in experienced animals, and counteracted the relapse-inducing effects of
      re-exposure to nicotine or nicotine-associated cues after a period of abstinence.
      In the central nervous system, clofibrate blocked nicotine's effects on neuronal
      firing in the ventral tegmental area and on dopamine release in the nucleus
      accumbens shell. All of these results suggest that fibrate medications might
      promote smoking cessation. The fact that fibrates are already approved for human
      use could expedite clinical trials and subsequent implementation of fibrates as a
      treatment for tobacco dependence, especially in smokers with abnormal lipid
      profiles.

PMID- 22453138
TI  - Activation of the orexin 1 receptor is a critical component of CO2-mediated
      anxiety and hypertension but not bradycardia.
AB  - Acute hypercapnia (elevated arterial CO(2)/H(+)) is a suffocation signal that is
      life threatening and rapidly mobilizes adaptive changes in breathing and
      behavioral arousal in order to restore acid-base homeostasis. Severe hypercapnia,
      seen in respiratory disorders (eg, asthma or bronchitis, chronic obstructive
      pulmonary disease (COPD)), also results in high anxiety and autonomic activation.
      Recent evidence has demonstrated that wake-promoting hypothalamic orexin (ORX:
      also known as hypocretin) neurons are highly sensitive to local changes in
      CO(2)/H(+), and mice lacking prepro-ORX have blunted respiratory responses to
      hypercapnia. Furthermore, in a recent clinical study, ORX-A, which crosses blood
      brain barrier easily, was dramatically increased in the plasma of patients with
      COPD and hypercapnic respiratory failure. This is consistent with a rodent model
      of COPD where chronic exposure to cigarette smoke led to a threefold increase in
      hypothalamic ORX-A expression. In the present study, we determined the role of
      ORX in the anxiety-like behavior and cardiorespiratory responses to acute
      exposure to a threshold panic challenge (ie, 20% CO(2)/normoxic gas). Exposing
      conscious rats to such hypercapnic, but not atmospheric air, resulted in
      respiratory, pressor, and bradycardic responses, as well as anxiety-like behavior
      and increased cellular c-Fos responses in ORX neurons. Systemically, pre-treating
      rats with a centrally active ORX1 receptor antagonist (30 mg/kg SB334867)
      attenuated hypercapnic gas-induced pressor and anxiety responses, without
      altering the robust bradycardia response, and only attenuated breathing responses
      at offset of the CO(2) challenge. Our results show that the ORX system has an
      important role in anxiety and sympathetic mobilization during hypercapnia.
      Furthermore, ORX1 receptor antagonists may be a therapeutic option rapidly
      treating increased anxiety and sympathetic drive seen during panic attacks and in
      hypercapnic states such as COPD.

PMID- 22453139
TI  - The motivation to self-administer is increased after a history of spiking brain
      levels of cocaine.
AB  - Recent attempts to model the addiction process in rodents have focused on cocaine
      self-administration procedures that provide extended daily access. Such
      procedures produce a characteristic loading phase during which blood levels
      rapidly rise and then are maintained within an elevated range for the duration of
      the session. The present experiments tested the hypothesis that multiple fast
      rising spikes in cocaine levels contribute to the addiction process more robustly
      than constant, maintained drug levels. Here, we compared the effects of various
      cocaine self-administration procedures that produced very different patterns of
      drug intake and drug dynamics on Pmax, a behavioral economic measure of the
      motivation to self-administer drug. Two groups received intermittent access
      (IntA) to cocaine during daily 6-h sessions. Access was limited to twelve 5-min
      trials that alternated with 25-min timeout periods, using either a hold-down
      procedure or a fixed ratio 1 (FR1). Cocaine levels could not be maintained with
      this procedure; instead the animals experienced 12 fast-rising spikes in cocaine
      levels each day. The IntA groups were compared with groups given 6-h FR1 long
      access and 2-h short access sessions and two other control groups. Here, we
      report that cocaine self-administration procedures resulting in repeatedly
      spiking drug levels produce more robust increases in Pmax than procedures
      resulting in maintained high levels of cocaine. These results suggest that rapid
      spiking of brain-cocaine levels is sufficient to increase the motivation to self
      administer cocaine.

PMID- 22453141
TI  - MicroRNAs and human cancer.
AB  - MicroRNAs (miRNAs) are a recently discovered family of short non-coding RNA
      molecules of about 19-24 nucleotides in length that are involved in regulation of
      gene expression. These small molecules have been found to regulate genes involved
      in diverse biological processes such as cell proliferation, development,
      differentiation, apoptosis and others. MiRNAs regulate gene expression at the
      post-transcriptional level either by inhibition of the target (mRNA) or by its
      destruction. Recent studies have shown that mRNA deregulation is a basic problem
      in studying pathogenesis of many malignant tumors. It has been recently shown
      that miRNAs are able to regulate thousands of target genes simultaneously. Thus,
      the key role of miRNA in carcinogenesis reveals a new layer in the molecular
      architecture of cancer. Patterns of altered miRNA expression in cancer may serve
      as molecular biomarkers for tumor diagnosis, prognosis of disease-specific
      outcomes, and prediction of therapeutic responses. Furthermore, miRNAs may serve
      as specific targets of new gene therapies.

PMID- 22453140
TI  - Sensitivity to cognitive effort mediates psychostimulant effects on a novel
      rodent cost/benefit decision-making task.
AB  - Amotivational states and insufficient recruitment of mental effort have been
      observed in a variety of clinical populations, including depression, traumatic
      brain injury, post-traumatic stress disorder, and attention deficit hyperactivity
      disorder. Previous rodent models of effort-based decision making have utilized
      physical costs whereas human studies of effort are primarily cognitive in nature,
      and it is unclear whether the two types of effortful decision making are
      underpinned by the same neurobiological processes. We therefore designed a novel
      rat cognitive effort task (rCET) based on the 5-choice serial reaction time task,
      a well-validated measure of attention and impulsivity. Within each trial of the
      rCET, rats are given the choice between an easy or hard visuospatial
      discrimination, and successful hard trials are rewarded with double the number of
      sugar pellets. Similar to previous human studies, stable individual variation in
      choice behavior was observed, with 'workers' choosing hard trials significantly
      more than their 'slacker' counterparts. Whereas workers 'slacked off' in response
      to administration of amphetamine and caffeine, slackers 'worked harder' under
      amphetamine, but not caffeine. Conversely, these stimulants increased motor
      impulsivity in all animals. Ethanol did not affect animals' choice but
      invigorated behavior. In sum, we have shown for the first time that rats are
      differentially sensitive to cognitive effort when making decisions, independent
      of other processes such as impulsivity, and these baseline differences can
      influence the cognitive response to psychostimulants. Such findings could inform
      our understanding of impairments in effort-based decision making and contribute
      to treatment development.

PMID- 22453142
TI  - Inhibition of TGFbeta signaling and its implications in anticancer treatments.
AB  - The transforming growth factor-beta (TGFbeta) is a potent regulator of
      tumorigenesis. In cancer, two distinctive behaviors of TGFbeta have been reported
      as a tumor suppressor at early stage of the disease, and as a tumor promoter at
      later stages. The past decades, the dualistic role of TGFbeta has garnered a lot
      of attention. As a result, cancer researchers' has been tasked to elucidate how
      TGFbeta signaling may lead to metastatic dissemination, how to tackle
      carcinogenesis and which therapeutic strategies should be adopted. Consequently,
      TGFbeta signaling pathways have been considered as appropriate targets for cancer
      therapy. The TGFbeta therapeutic strategies have emerged at three levels: ligand,
      ligand-receptor interaction and intracellular signaling level. Promising
      inhibitors of TGFbeta signaling have entered clinical trials and shown
      encouraging results. Here we review the three strategies of TGFbeta signa-ling
      inhibition and theirs applications in treatment of cancer.

PMID- 22453143
TI  - Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma.
AB  - OBJECTIVES: Metformin, the most used oral antidiabetic drug for the treatment of
      type 2 diabetus mellitus, has proved encouraging results when used in the
      treatment of various types of cancer such as triple-negative breast cancer.
      Despite compelling evidence of a role of metformin as an anticancer drug, the
      mechanisms by which metformin exerts its oncostatic actions are not fully
      understood yet. Therefore, we tried to bring new insights by analyzing the anti
      neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like
      cells treated with conventional combination chemotherapy. METHODS: Cancer stem
      like cells previusly isolated from a hepatocellular carcinoma biopsy were treated
      with metformin, PIAF chemotherapy regimen and the combination of these two
      protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein
      diacetate and proliferation rates were determined, apart from the autophagy assay
      and apoptosis determination by chip flow cytometry. RESULTS: Metformin alone and
      especially metformin in association with PIAF increases oxidative stress within
      the cells by increasing the levels of lipid peroxids as well as decreasing the
      levels of reduced glutathione. The MTT cell proliferation assay showed decreased
      prolife-ration rates for the arm treated with metformin and with the combination
      of drugs in comparison with the control arm, proving high correlation with the
      oxidative stress results. The autophagy assay and determination of apoptosis by
      chip flow cytometry confirmed the results obtained in the previous assays.
      CONCLUSION: Metformin could be used in chemotherapy treatments to induce reactive
      oxygen species and increase the cytostatics effects within the tumor cell. Still,
      further experiments must be carried out on murine models before we can move on
      and use this drugs in the adjuvant setting for unresectable primary liver cancer.

PMID- 22453144
TI  - Gold nanoparticles synthesis and biological activity estimation in vitro and in
      vivo.
AB  - The aim of the work was the synthesis of gold nanoparticles (GNP) of different
      sizes and the estimation of their biological activity in vitro and in vivo.
      MATERIALS AND METHODS: Water dispersions of gold nanoparticles of different sizes
      have been synthesized by Davis method and characterized by laser-correlation
      spectroscopy and transmission electron microscopy methods. The GNP interaction
      with tumor cells has been visualized by confocal microscopy method. The enzyme
      activity was determined by standard biochemical methods. GNP distribution and
      content in organs and tissues have been determined via atomic-absorption
      spectrometry method; genotoxic influence has been estimated by "Comet-assay"
      method. RESULTS: The GNP size-dependent accumulation in cultured U937 tumor cells
      and their ability to modulate U937 cell membrane Na(+),K(+)-ATR-ase activity
      value has been revealed in vitro. Using in vivo model of Guerin carcinoma it has
      been shown that GNP possess high affinity to tumor cells. CONCLUSIONS: Our
      results indicate the perspectives of use of the synthesized GNP water dispersions
      for cancer diagnostics and treatment. It's necessary to take into account a size
      dependent biosafety level of nanoparticles.

PMID- 22453145
TI  - Production of nitrogen oxide derivatives under the influence of NO-synthase
      inhibitors and natural compounds in mice with transplanted tumors.
AB  - AIM: The aim of the present study was to investigate the dynamics of nitric oxide
      derivative (NOD) formation in mice with transplanted tumors and to analize
      whether synthetic NO-synthase inhibitors, NO-donors and natural compounds could
      modulate NOD synthesis. MATERIALS AND METHODS: In the study F(1)(C(57)BlxCBA),
      CBA/Lac, BDF and Balb/c mice were used. Endogenous NOD synthesis in mice with
      transplanted Ehrlich carcinoma (EC) and Lewis lung carcinoma (LLC) was estimated
      by measuring urine nitrates (NA) and nitrites (NI) excretion and their
      concentration in tumor tissue determined by cadmium-reduction method. RESULTS: It
      is shown that EC development is accompanied by increased endogenous NOD formation
      whereas LLC growth - by its decrease. Total NOD excretion with urine in EC
      bearing mice during tumor development was in the range of 1.1x10(-7)-7.0x10(-6)
      mol/kg body weight that was 1.7-6.8 times higher than that in LLC-bearing mice.
      Treatment of EC-bearing animals with N(omega)-nitro-L-arginine and aminoguanidine
      resulted in decreased NOD formation causing moderate tumor growth retardation.
      Effect of treatment with nitroprusside was shown to be dependent on the rout of
      its administration and dosage. Treatment of EC-bearing mice with picnogenol,
      tannic acid, spirulina and paprika enriched with selenium resulted in tumor
      growth inhibition at the early stage of EC growth accompanied by stimulation of
      endogenous NOD formation. CONCLUSION: Regulation of endogenous NOD formation
      towards normal physiological levels or hyperproduction of these compounds may
      result in tumor growth suppression.

PMID- 22453146
TI  - The long-range cytotoxic effect in tumor-bearing animals.
AB  - AIM: The relationship between cancer and patient health is still of great
      interest for experimental and clinical oncology. The tumor can adversely affect
      surrounding and distant tissues as well. However, effects of the tumor on distant
      tissues are much less studied than its effects on surrounding tissues. This study
      was aimed to test whether the tumor could trigger cytotoxic and/or genotoxic
      signals with respect to the distant proliferative tissue such as bone marrow.
      MATERIALS AND METHODS: Rats were subcutaneously implanted with Guerin carcinoma
      cells, and on the 12(th) and 18(th) days after implantation both cytotoxic and
      genotoxic effects were assessed by flow cytometry in acridine orange stained
      unfractionated bone marrow cells isolated from femur. The cytotoxic effect was
      assessed using ratios of the following cell populations: total nucleated cells
      (TNC)/total enucleated erythrocytes (TE); polychromatic erythrocytes
      (PCE)/normochromatic erythrocytes (NCE). The genotoxic effect was assessed by
      quantification of micronucleated PCE (MNPCE) within the population of PCE.
      RESULTS: A significant cytotoxic effect was observed in tumor-bearing animals on
      the 12(th) and 18(th) days after implantation (~ 2-fold decrease in both TNC/TE
      and PCE/NCE ratios compared with corresponding parameters in control animals).
      There was also a genotoxic effect in these animals (a slight increase in the
      number of MNPCE), however, this effect was insignificant. The PCE/NCE ratio
      reversely correlated with the tumor weight which is suggestive of the link
      between erythropoietic cytotoxicity and tumor progression. CONCLUSION: Cytotoxic
      insult to the bone marrow is likely to be associated with the mechanism(s)
      triggered by distantly located tumors whose growth may correlate with the
      cytotoxic effect.

PMID- 22453147
TI  - Regulatory T cells but not NKT I cells are modulated by a single low-dose
      cyclophosphamide in a B cell lymphoma tumor-model.
AB  - AIM: Experimental and clinical studies showed that the administration of
      cyclophosphamide (Cy) in low doses leads to an enhancement of the antitumor
      immune response. Our objective was to study the modulation, if any, by low dose
      Cy, of T regulatory (Treg) and natural killer T (NKT) I cells, two cell
      populations of the innate immune response with opposing effects on the tumors, in
      a rat B cell lymphoma model. METHODS: Inbred e rats were challenged s.c. with L
      TACB lymphoma and on day 14 animals were distributed in two groups. Treated:
      injected i.p. with cyclophosphamide (10mg/kg of body weight) and CONTROL:
      injected i.p. with saline. Blood samples were taken from days 0 to 21 and the
      percentage of T regulatory and natural killer T I cells were determined by flow
      cytometry. RESULTS: We found that the increase of natural and inducible T
      regulatory cells of peripheral blood achieved during tumor growth was
      significantly downregulated by cyclophosphamide. On the contrary, natural killer
      T I cells were not modulated by the treatment. CONCLUSION: The antimetastatic
      effect of a single low dose of Cy would be due, at least in part, to
      downregulation of natural and inducible T regulatory cells.

PMID- 22453148
TI  - Polymorphisms of MTHFR and MTR genes are not related to susceptibility to
      childhood ALL in North India.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most worldwide common type
      of childhood cancer. Methylenetetrahydrofolate reductase (MTHFR) and 5
      methyltetrahydrofolate-homocysteine methyltransferase (MTR) participate in folate
      pathways and are known as critical factors for DNA integrity as well as DNA
      hypomethylation. The aim of this work is to investigate frequency of MTHFR (677C
      >T and 1298A->C) and MTR (2756A->G) polymorphisms and their interaction with
      respect to possible effect on risk of childhood ALL among North Indian
      population. PROCEDURE: A case control study from has been conducted on bone
      marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched
      healthy controls using PCR-RFLP method. RESULTS: No statistically significant
      differences were observed for different genotypes between patients and controls
      (p>0.05). Significant difference for the risk of ALL in individuals having
      genotype of MTHFR 677TT (OR=0.61, 95% CI=0.21-1.77) and MTHFR 1298CC (OR=0.56,
      95% CI=0.18-1.68) was not observed. The correlation of SNP of MTR gene and risk
      of ALL was not observed, too. CONCLUSIONS: The differences in distribution of
      possible combined genotypes of MTHFR (677C->T, 1298A->C) and MTR (2756A->G)
      between ALL patients and controls were statistically insignificant.

PMID- 22453149
TI  - Novel germline MLH1 and MSH2 mutations in Latvian Lynch syndrome families.
AB  - BACKGROUND/AIMS: Hereditary non-polyposis colorectal cancer or Lynch syndrome is
      an autosomal dominantly inherited disease with high penetrance, mostly due to
      mutations in the MLH1 and MSH2 genes. The aim of this study is to investigate the
      mutation spectrum of the MLH1 and MSH2 genes. METHODOLOGY: High risk colorectal
      cancer families were selected from overall 1053 consecutive patients. Screening
      of germline mutations in the MLH1 and MSH2 was performed by direct sequencing and
      multiplex ligation-dependent probe amplification. RESULTS: Ten patients fulfilled
      the Amsterdam I/II criteria and Bethesda guidelines of the Lynch syndrome. Three
      novel mutations were identified in MLH1 and MSH2 genes, as well as two known
      mutations in the MLH1 gene. Large rearrangements in the MLH1 gene were found in
      two patients. CONCLUSIONS: The mutations in the MLH1 and MSH2 genes in Latvian
      high-risk families are highly heterogeneous. Combination of direct sequencing and
      MLPA is the most appropriate molecular method of detecting hereditary
      nonpolyposis colorectal cancer patients and family members at risk.

PMID- 22453150
TI  - Influence of surgical resection on plasma endoglin (CD105) level in non-small
      cell lung cancer patients.
AB  - BACKGROUND AND AIM: Endoglin is a proliferation-associated antigen on endothelial
      cells and essential for angiogenesis. Soluble endoglin (s-endoglin), formed by
      proteolytic cleavage of ectodomain of membrane receptor could be an indicator of
      tumor-activated endothelium. The aim of present study was to analyze changes of s
      endoglin level in plasma of lung cancer patients following surgical resection and
      to estimate the correlation of s-endoglin with other soluble receptors, sTie2 and
      sVEGF R1. PATIENTS AND METHODS: The study group consisted of 37 patients with
      stage I of non-small cell lung cancer. Plasma concentrations of s-endoglin, sTie2
      and sVEGF R1 were evaluated by ELISA, three times: before surgical resection and
      on postoperative day 7 and 30. RESULTS: The median of s-endoglin concentration
      decreased significantly on postoperative day 7 when compared with preoperative
      level and next increased on 30(th) day and it was comparable with that before
      surgery. s-Endoglin correlated with another soluble receptors, with sTie2 both
      before surgery (r=0.44) and on postoperative day 7 (r=0.52) and on 30(th) day
      (r=0.58), with sVEGF R1 - only on postoperative day 7 (r=0.75). CONCLUSION: The
      increased level of serum endoglin in lung cancer patients compared to controls
      and its changes after surgical treatment suggest potential application of soluble
      form of endoglin as potential tumor marker.

PMID- 22453151
TI  - Gene expression profiling of B-CLL in Ukrainian patients in post-Chernobyl
      period.
AB  - BACKGROUND: Genetic mechanisms that result in the development and progression of
      B-cell chronic lymphocytic leukemia (B-CLL) are mainly unknown. We have analyzed
      gene expression patterns in Ukrainian B-CLL patients with the aim of identifying
      B-CLL involved / associated genes in order to shed light on the biology of this
      pathological entity. MATERIAL AND METHODS: The samples of the peripheral blood
      and bone marrow of 44 Ukrainian B-CLL patients with no characteristics indicative
      of unfavorable course of the disease such as CD38 were analyzed morphologically
      and immunocytochemically according to the new WHO classification. Total RNA was
      isolated, and gene expression levels were determined by microarray method
      comparing with the sample from 17 healthy donors. RESULTS: We investigated
      interactions using the Ingenuity Pathway Analysis (IPA) software and found 1191
      network eligible up-regulated genes and 3398 Functions/Pathways eligible up
      regulated genes, 1225 network eligible down-regulated genes and 2657
      Functions/Pathways eligible down-regulated genes. CONCLUSION: In B-CLL patients,
      gene networks around MYC, HNF1A and HNF4A, YWHAG, NF-kappaB1 and SP1 are
      identified as up-regulated; CEBPA, YWHAG, SATB1 and RB1 -- as down-regulated. G
      protein coupled receptor signaling, arachidonic acid and linoleic acid
      metabolisms, calcium signaling, metabolism of xenobiotics by cytochrome P450 are
      found out as significant up-regulated pathways. EIF2 and Cdc42 signaling,
      regulation of eIF4 and p70S6k signaling, protein ubiquitination pathway and
      oxidative phosphorylation are the most significant down-regulated pathways
      obtained in our study. The involvement of NF-kappaB gene network and upregulated
      levels of G protein coupled receptor signaling pathway, which has an important
      role in transcription of NF-kappaB, are important and need further examination.

PMID- 22453152
TI  - Cancer with unknown primary: finding a needle in a hay stack.
AB  - Detection and resection of small neuroendocrine tumours (NET) is like finding a
      needle in a hay stack. Use of specific tracers such as (68)Ga-DOTATOC in a PET/CT
      study has been proven to have a high sensitivity and specificity to cells
      expressing somatostatin-SSR receptors. The use of (99m)Tc-Octreotide to detect
      neuroendocrine tumours during surgery is an effective adjunct for therapy. We
      here present a clinical case of patient with NET where these modalities help in
      both diagnostic and therapeutic surgery.

PMID- 22453154
TI  - Review of manuscripts.

PMID- 22453153
TI  - Accelerated rejection of the second transplants of immunogenic tumor in mice
      under inhibition of indoleamine 2,3-dioxygenase activity by ethyl pyruvate.
AB  - AIM: A recently discovered enzyme, indoleamine 2,3-dioxygenase (IDO), is
      expressed in placenta, dendritic cells and also in many kinds of tumors and in
      tumor-infiltrating macrophages. By catabolizing tryptophan, IDO causes local
      depletion of this essential amino acid and excess of kinurenin, and suppresses in
      situ proliferation and functioning of T lymphocytes. Thus, immune resistance of
      tumors can be overcome by inhibiting IDO activity. MATERIALS AND METHODS: C3HA
      mice immunized with non-syngeneic H-29 tumor were used to study the effect of the
      IDO inhibitor ethyl pyruvate, under systemic or local (at site of tumor cells
      localization) administration, on the occurrence and rate of rejection of the
      second transplants of this tumor. RESULTS: Both systemic and local administration
      of ethyl pyruvate increases the incidence of and substantially accelerates tumor
      regression as compared with control. CONCLUSION: IDO inhibitors impairing immune
      resistance of tumors may appear useful in leveraging the efficacy of antitumor
      therapy.

PMID- 22453155
TI  - Pathophysiology of pelvic organ prolapse.

PMID- 22453156
TI  - Symptom-based, clinical, and urodynamic diagnoses of urinary incontinence: how
      well do they correlate in postmenopausal women?
AB  - OBJECTIVE: : The objective of this study was to determine the correlation between
      symptom-based, clinical, and urodynamic (UD) diagnoses of urinary incontinence in
      postmenopausal women. METHODS: : This is a review of results of UD findings in
      postmenopausal women with signs and/or symptoms of urinary incontinence. Positive
      predictive values (PPVs) were calculated for symptom-based and clinically
      assigned diagnoses by subtype of incontinence and UD diagnosis. RESULTS: : A
      total of 105 postmenopausal women with signs and/or symptoms of urinary
      incontinence underwent UD testing. Subjects were predominantly white (95.1%),
      with average age 61 (SD, +/-9). Overall, symptom diagnosis matched UD diagnosis
      27% of the time. Similarly, clinical diagnosis matched UD diagnosis 27% of the
      time. All 3 diagnoses (symptom, clinical, and UD) matched 18% of the time. Report
      of urine loss with Valsalva had a PPV of 0.57, for UD diagnosis of stress
      incontinence. For symptoms of urge and mixed incontinence, PPVs were 0.22 and
      0.11, respectively. Clinical diagnoses of stress, urge, and mixed incontinence as
      compared with UD diagnosis showed PPVs of 0.64, 0.30, and 0.09, respectively. PPV
      for any UD diagnosis of incontinence was 0.69 by symptoms and 0.71 by clinical
      evaluation. CONCLUSIONS: : The correlation between type of urinary incontinence
      based on symptoms, clinical evaluation, and UD findings is poor overall in
      postmenopausal women. It is highest with stress and lowest with mixed
      incontinence. The voiding diary and cough stress test are valuable tools in
      predicting type of incontinence by UD testing.

PMID- 22453157
TI  - Characteristics of physicians who choose fellowship training in obstetrics and
      gynecology.
AB  - INTRODUCTION: : To determine the attributes and motivation of physicians who
      pursue fellowship training in the subspecialties of Obstetrics and Gynecology
      (Ob/Gyn). METHODS: : We surveyed current fellows and recent graduates from the
      ABOG recognized subspecialties in Ob/Gyn. Demographics and reasons for pursuing
      fellowship training were obtained. Significant differences between and among
      groups were determined using the Mann-Whitney U test and Pearson chi test.
      RESULTS: : Forty-two percent of those sent a survey responded. The majority were
      between ages 30 to 35 (65.7%), female (60.5%), married (74.5%), and White
      (68.8%). Over 55% in each subspecialty cited interest in subject area as the
      primary reason for choosing their fellowship. CONCLUSION: : Interest in subject
      remains the primary motivation for the majority of physicians choosing
      subspecialty fellowship training in Ob/Gyn. There is considerably more variation
      regarding what physicians' secondary motivation is and these reasons appear to
      vary according to the particular subspecialty.

PMID- 22453158
TI  - A comparison of transobturator versus retropubic midurethral slings for mixed
      urinary incontinence.
AB  - PURPOSE: : The primary objective of this study was to compare improvement and/or
      cure of mixed urinary incontinence (MUI) symptoms after retropubic (RP) versus
      transobturator (TO) slings. The secondary objective was to compare improvement
      and/or cure of the urge urinary incontinence (UUI) component of MUI. METHODS: :
      This retrospective cohort study included all patients with MUI who underwent a
      midurethral sling from January 2006 to May 2007. IRB approval was obtained to
      perform telephone interviews to collect the Patient Global Impression of
      Improvement (PGI-I) questionnaire for MUI and to elicit any changes in the SUI
      and/or UUI components of MUI. The primary outcome was based on a 7-point Likert
      scale for the PGI-I questionnaire. The secondary outcome was improvement or
      resolution of the UUI component of MUI based on a 4-point Likert scale of patient
      responses to the question, "Is your urge incontinence worse, the same, or
      improved after surgery?" Subjects who had RP slings were compared with those with
      TO with respect to these outcomes. Patient satisfaction, adverse events, urinary
      retention, and worsening of urge incontinence symptoms were also assessed.
      RESULTS: : For the primary outcome (MUI), no significant difference was found in
      the PGI-I scores between the 2 groups. Similarly, no difference was found in UUI
      improvement/resolution between the 2 groups. UUI improvement was noted in 46.4%
      of the TO group and 56.5% of the RP group, and UUI cure in 39.3% of the TO group
      and 26.1% of the RP group. An 84.3% overall improvement/cure rate of UUI was
      noted when both groups were combined. Ten (19.6%) women required anticholinergic
      use after slings. A total of 52.6% of subjects were "completely satisfied" and
      14.3% were "not at all satisfied" with the procedure in the TO group, versus
      65.2% and 7.7% in the RP group (Mann-Whitney U test, P = 0.23). There was no
      difference in perioperative adverse events between the 2 groups. CONCLUSIONS: :
      RP and TO slings result in similar global improvement in MUI symptoms. A total of
      84.3% of patients undergoing RP or TO sling for MUI have improvement/cure of the
      UUI component.

PMID- 22453159
TI  - Robotic sacrocolpopexy versus vaginal colpopexy with mesh: choosing the right
      surgery for anterior and apical prolapse.
AB  - OBJECTIVES: : To describe patients' characteristics and anatomic outcome of
      robotic sacrocolpopexy (RSC) and vaginal mesh colpopexy (VMC). METHODS: :
      Retrospective cohort study involving RSC (n = 17) and VMC (n = 37) procedures
      performed over an 18 month period in a teaching hospital. The primary outcome was
      1 year anatomic cure at the apex and anterior wall. Descriptive and univariate
      analyses were used to determine statistical significance (P < 0.05). RESULTS: :
      VMC subjects were more likely to be older, menopausal, and had increased BMI and
      more severe prolapse than the RSC group. At a mean follow-up of 13 and 12.3
      months for the VMC and RSC, respectively, both groups showed significant
      improvement of prolapse (P < 0.001) with a cure rate of 94.1% for RSC and 70.2%
      for VMC (P = 0.07). Total vaginal length was significantly shorter after VMC. RSC
      had longer operative time and hospital stay, but lower blood loss. Complication
      rates were similar among the groups. CONCLUSIONS: : RSC and VMC are being offered
      to different patient populations. These minimally invasive prolapse repair
      procedures have comparable results with a trend toward higher cure rate in RSC
      and similar complications rate.

PMID- 22453160
TI  - Incidental cystotomy at the time of a hysterectomy.
AB  - OBJECTIVES: : To evaluate risk factors for incidental cystotomy at the time of a
      hysterectomy. METHODS: : All hysterectomies performed between January 1, 2000 and
      May 31, 2004 were reviewed. Demographic and operative data were abstracted from
      medical records. Cases were patients with cystotomies while controls were those
      without bladder injury. Categorical variables were analyzed with the chi or
      Fisher exact test (where applicable) while the Student t test was used for
      continuous data. Logistic regression was used for multivariate analysis. RESULTS:
      : During the study period, 1424 hysterectomies were performed (50% abdominally,
      45% vaginally, and 5% laparoscopically assisted vaginal). Thirty-four (2.4%)
      cystotomies occurred. Risk factors for incidental cystotomy included prior
      cesarean delivery (adjusted OR: 2.86, 95% CI: 1.39-5.92), pelvic adhesions
      (adjusted OR: 2.43, 95% CI: 1.11-5.31), and vaginal hysterectomy (adjusted OR:
      2.63, 95% CI: 1.18-5.87). CONCLUSIONS: : Prior cesarean delivery, pelvic adhesive
      disease, and vaginal hysterectomy are independent risk factors for incidental
      cystotomy at the time of a hysterectomy.

PMID- 22453161
TI  - Outcomes of revision perineoplasty for persistent postpartum dyspareunia.
AB  - OBJECTIVE: : To determine outcomes of revision perineoplasty for women with
      persistent pain and anatomic distortion of the perineum following obstetric
      perineal laceration repair. METHODS: : A prospective cohort study of 9 women who
      underwent revision perineoplasty for persistent dyspareunia and perineal scarring
      was performed. Symptoms of perineal pain, coital activity, dyspareunia, impact on
      self-esteem, and vaginal scarring were compared. Statistical analysis was
      performed using paired t-tests. RESULTS: : All women had anatomic distortion of
      the perineum prior to surgical revision. Postoperatively, no woman had persistent
      scarring or granulation tissue. There was a significant decline in perineal pain
      from 6.1 +/- 2.89 to 0.5 +/- 1.13 (P = 0.02) and 89% of subjects reported an
      increase in coital frequency and satisfaction (P = 0.0002). An improvement in
      self-esteem and lifestyle were reported by 77% and 89%, respectively. CONCLUSION:
      : In women with dyspareunia and perineal defects following perineal laceration
      repair, early consideration should be made for revision perineoplasty as a
      significant impact is noted on sexual function and quality of life.

PMID- 22453162
TI  - Traumatic bladder rupture following vaginal hysterectomy.
AB  - Although complications associated with vaginal hysterectomy are rare, the most
      common complications involve bladder injury. These injuries are sustained most
      commonly during mobilization of the posterior bladder wall off of the lower
      uterine segment, particularly in the setting of adhesions from prior cesarean
      sections. Bladder injuries may present with urinary retention, gross hematuria,
      serum electrolyte, and creatinine abnormalities, a bowel ileus or abdominal pain.
      This report describes a patient who underwent a total vaginal hysterectomy
      complicated by an unrecognized bladder injury, rupture, and subsequent
      abdominopelvic urinoma, requiring surgical drainage and repair.

PMID- 22453163
TI  - Illustrated medication instructions as a strategy to improve medication
      management among Latinos: a qualitative analysis.
AB  - Although illustrated medication instructions may improve medication management
      among vulnerable populations, little prior research has evaluated their use among
      Latinos. We conducted focus groups and interviews with Latino patients with
      diabetes at two safety net clinics in Tennessee to understand medication taking
      practices and perceptions of illustrated medication instructions. Patients
      reported confidence in being able to take medications, but demonstrated a lack of
      understanding of medication instructions. On further probing, they described
      several barriers to effective medication management rooted in poor communication.
      Patients expressed preference for illustrated medication instructions which could
      address several of the challenges raised by patients.

PMID- 22453164
TI  - The structure of coping among older adults living with HIV/AIDS and depressive
      symptoms.
AB  - One-third of adults living with HIV/AIDS are over the age of 50. This study
      evaluated the structure of coping among 307 older adults living with HIV/AIDS.
      Participants completed 61 coping items and measures of anxiety, depression,
      loneliness, and coping self-efficacy. Exploratory factor analyses retained 40
      coping items loading on five specific first order factors (Distancing Avoidance,
      Social Support Seeking, Self-Destructive Avoidance, Spiritual Coping, and
      Solution-Focused Coping) and two general second order factors (Active and
      Avoidant Coping). Factors demonstrated good reliability and validity. Results
      suggest that general coping factors should be considered with specific factors
      when measuring coping among older adults.

PMID- 22453165
TI  - Anxiety and depression are independent predictors of quality of life of patients
      with chronic musculoskeletal pain.
AB  - We examined the relative impact of baseline anxiety, depression and fear of
      movement on health related quality of life at 12-month follow-up after a
      multidisciplinary pain management programme. One hundred and eleven patients who
      had chronic musculoskeletal pain (mean age 45 years, 65% women) attended during
      2003-2005 a multidisciplinary three-phase pain management programme with a total
      time frame of six to seven months, totalling 19 days. The Beck Anxiety Inventory
      was used to rate anxiety, the Beck Depression Inventory depression, the Tampa
      Scale of Kinesiophobia fear of movement. The generic 15D questionnaire was used
      to assess health related quality of life. Baseline data were collected at
      admission, follow-up data at 12 months. Mean health related quality of life
      increased significantly from baseline to 12-month follow-up. Anxiety at baseline
      predicted significant negative change in the health related quality of life,
      depression predicted significant positive change in the health related quality of
      life. Fear of movement did not predict any significant change in the health
      related quality of life. We concluded that patients with chronic musculoskeletal
      pain and mild to moderate depression benefit from a multidisciplinary pain
      management programme in contrast to anxious patients. The findings imply further
      research with bigger sample sizes, other than HRQoL outcome measures as well as
      with other groups of patients.

PMID- 22453168
TI  - Chairman's Message.

PMID- 22453166
TI  - Being men with eating disorders: perspectives of male eating disorder service
      users.
AB  - This study aimed to explore experiences of men currently using eating disorder
      services. Eight men from two eating disorder services were interviewed about
      their experiences of seeking and receiving treatment. Two superordinate themes
      emerged from Interpretative Phenomenological Analysis: (1) difficulty seeing self
      as having an eating disorder; and (2) experiences of treatment: how important is
      gender? The underlying themes varied in their specificity to men, with some
      echoing findings from the female eating disorder literature. Difficulty admitting
      the eating disorder may link with eating disorder psychopathology as well as
      gender-specific issues. Implications for clinical practice and future research
      are discussed.

PMID- 22453169
TI  - Harnessing prions as test agents for the development of broad-range
      disinfectants.
AB  - The development of disinfectants with broad-range efficacy against bacteria,
      viruses, fungi, protozoa and prions constitutes an ongoing challenge. Prions, the
      causative agents of transmissible spongiform encephalopathies (TSEs) such as
      Creutzfeldt-Jakob disease (CJD) or its variant (vCJD) rank among the pathogens
      with the highest resistance to disinfection. Pilot studies have shown that
      procedures devised for prion disinfection were also highly effective against
      microbial pathogens. This fueled the idea to systematically exploit prions as
      test pathogens for the identification of new potential broad-range disinfectants.
      Prions essentially consist of misfolded, aggregated prion protein (PrP) and
      putatively replicate by nucleation-dependent, or seeded PrP polymerization.
      Recently, we have been able to establish PrP seeding activity as a quantitative
      in vitro indicator for the disinfection of 263K scrapie prions on steel wires
      used as surrogates for medical instruments. The seeding activity on wires re
      processed in different disinfectants could be (1) biochemically determined by
      quantitative protein misfolding cyclic amplification (qPMCA), (2) biologically
      detected after qPMCA in a cell assay and (3) correctly translated into residual
      titres of scrapie infectivity. Our approach will substantially facilitate the
      identification of disinfectants with efficacy against prions as promising
      candidates for a further microbiological validation of broad-range activity.

PMID- 22453170
TI  - Global Alzheimer Research Summit: basic and clinical research: present and future
      Alzheimer research.
AB  - We report here on the proceedings of the Global Alzheimer Summit that took place
      September 22-23, 2011 in Madrid, Spain. As Alzheimer disease (AD) is the leading
      cause of neurodegeneration in elderly individuals and as yet has no effective
      therapeutic option, it continues to stimulate global research interests. At the
      conference, leaders in the field of AD research provided insights into current
      developments in various areas of research, namely molecular mechanisms, genetics,
      novel aspects of AD research and translational research. Emphasis was also placed
      on the importance of biomarkers in the diagnosis of AD and development of current
      therapeutic strategies.

PMID- 22453171
TI  - Lichens: unexpected anti-prion agents?
AB  - The prion diseases sheep scrapie and cervid chronic wasting disease are
      transmitted, in part, via an environmental reservoir of infectivity; prions
      released from infected animals persist in the environment and can cause disease
      years later. Central to controlling disease transmission is the identification of
      methods capable of inactivating these agents on the landscape. We have found that
      certain lichens, common, ubiquitous, symbiotic organisms, possess a serine
      protease capable of degrading prion protein (PrP) from prion-infected animals.
      The protease functions against a range of prion strains from various hosts and
      reduces levels of abnormal PrP by at least two logs. We have now tested more than
      twenty lichen species from several geographical locations and from various taxa
      and found that approximately half of these species degrade PrP. Critical next
      steps include examining the effect of lichens on prion infectivity and cloning
      the protease responsible for PrP degradation. The impact of lichens on prions in
      the environment remains unknown. We speculate that lichens could have the
      potential to degrade prions when they are shed from infected animals onto lichens
      or into environments where lichens are abundant. In addition, lichens are
      frequently consumed by cervids and many other animals and the effect of dietary
      lichens on prion disease transmission should also be considered.

PMID- 22453172
TI  - Chronic wasting disease: fingerprinting the culprit in risk assessments.
AB  - Transmissible spongiform encephalopathies (prion diseases) in animals may be
      associated with a zoonotic risk potential for humans as shown by the occurrence
      of variant Creutzfeldt-Jakob disease in the wake of the bovine spongiform
      encephalopathy epidemic. Thus, the increasing exposure of humans in North America
      to cervid prions of chronic wasting disease (CWD) in elk and deer has prompted
      comprehensive risk assessments. The susceptibility of humans to CWD infections is
      currently under investigation in different studies using macaques as primate
      models. The necessity for such studies was recently reinforced when disease
      associated prion protein and its seeding activity were detected in muscles of
      clinically inconspicuous CWD-infected white-tailed deer. Increasing evidence
      points to the existence of different CWD strains, and CWD prions may also change
      or newly emerge over time. Therefore, CWD isolates examined in macaques should be
      characterized as precisely as possible for their molecular identity. On this
      basis other CWD field samples collected in the past, present or future could be
      systematically compared with macaque-tested inocula in order to assess whether
      they are covered by the ongoing risk assessments in primates. CWD typing by
      Fourier transform-infrared spectroscopy of pathological prion protein may provide
      a method of choice for this purpose.

PMID- 22453173
TI  - Two-steps control of cellular prion physiology by the extracellular regulated
      kinase-1 (ERK1).
AB  - Cellular prion (PrP(c)) undergoes a regulated alpha-secretase-like cleavage by
      the disintegrin ADAM17 similar to the one taking place on beta-amyloid precursor
      protein (betaAPP). Because these cleavages give rise to biologically active
      fragments, understanding their regulation could be of importance. We have
      established that the Extracellular Regulated Kinase-1 (ERK1) controls PrPc
      processing by modulating ADAM17 phosphorylation in a protein kinase C-dependent
      manner. Strikingly, we also demonstrated that ERK1 acts upstream to increase
      PrP(c) promoter transactivation in an AP-1 dependent manner. Therefore, ERK1
      exerts a dual control of both PrP(c) metabolism and expression. Interestingly,
      alpha-secretase cleavage of betaAPP appears to be independent of ERK1. I describe
      here similarities and differences in alpha-secretase-mediated PrP(c) and betaAPP
      processing pathways and discuss putative physiopathological implications.

PMID- 22453174
TI  - Insights into the disparate action of osmolytes and macromolecular crowders on
      amyloid formation.
AB  - It is widely recognized that amyloid formation sensitively responds to conditions
      set by myriad cellular solutes. These cosolutes include two important classes:
      macromolecular crowders and compatible osmolytes. We have recently found that
      addition of macromolecular PEG only slightly affects fibril formation of a model
      peptide in vitro. Polyol osmolytes, in contrast, lengthen the lag time for
      aggregation, and lead to larger fibril mass at equilibrium. To further
      hypothesize on the molecular underpinnings of the disparate effect of the two
      cosolute classes, we have further analyzed the experiments using an available
      kinetic mechanism describing fibril aggregation. Model calculations suggest that
      all cosolutes similarly lengthen the time required for nucleation, possibly due
      to their excluded volume effect. However, PEGs may in addition promote fibril
      fragmentation, leading to lag times that are overall almost unvaried. Moreover,
      polyols effectively slow the monomer-fibril detachment rates, thereby favoring
      additional fibril formation. Our analysis provides first hints that cosolutes act
      not only by changing association or dissociation rates, but potentially also by
      directing the formation of fibrils of varied morphologies with different
      mechanical properties. Although additional experiments are needed to
      unambiguously resolve the action of excluded cosolutes on amyloid formation, it
      is becoming clear that these compounds are important to consider in the search
      for ways to modulate fibril formation.

PMID- 22453175
TI  - Misfolded PrP and a novel mechanism of proteasome inhibition.
AB  - Prion diseases comprise a family of fatal neurodegenerative disorders caused by
      the conformational re-arrangement of a normal host-encoded protein, PrP (C) , to
      an abnormal infectious isoform termed PrP (Sc) . Currently, the precise cellular
      mechanism(s) underlying prion disease pathogenesis remain unclear. Evidence
      suggests a role for the ubiquitin proteasome system (UPS), a protein degradation
      pathway that is critical for maintaining cellular proteostasis. Dysfunction of
      the UPS has been implicated in various neurodegenerative diseases. However, the
      mechanisms of this impairment remain unknown in many cases, and evidence that
      disease-associated misfolded proteins are able to directly inhibit the function
      of the proteasome has been lacking. Recently, we have shown data describing a
      mechanism of proteasome impairment by the direct interaction of beta-sheet-rich
      PrP to reduce gate opening and inhibit substrate entry. This novel mechanism may
      provide a model for how other misfolded, disease-associated proteins might
      interact with the proteasome to disrupt its function. Targeting the UPS to
      restore proteostasis in neurodegenerative disorders in which misfolded proteins
      accumulate offers a possible target for therapeutic intervention.

PMID- 22453176
TI  - Early structural features in mammalian prion conformation conversion.
AB  - The conversion to a disease-associated conformer (PrP(Sc)) of the cellular prion
      protein (PrP(C)) is the central event in prion diseases. Wild-type PrPC converts
      to PrP(Sc) in the sporadic forms of the disorders through an unknown mechanism.
      These forms account for up to 85% of all human (Hu) occurrences; the infectious
      types contribute for less than 1%, while genetic incidence of the disease is
      about 15%. Familial Hu prion diseases are associated with about forty point
      mutations of the gene coding for the PrP denominated PRNP. Most of the variants
      associated with these mutations are located in the globular domain of the
      protein. In a recent work in collaboration with the German Research School for
      Simulation Science, in Julich, Germany, we performed molecular dynamics
      simulations for each of these mutants to investigate their structure in aqueous
      solution. Structural analysis of the various point mutations present in the
      globular domain unveiled common folding traits that may allow to a better
      understanding of the early conformational changes leading to the formation of
      monomeric PrP(Sc). Recent experimental data support these findings, thus opening
      novel approaches to determine initial structural determinants of prion formation.

PMID- 22453177
TI  - Ion channels induced by the prion protein: mediators of neurotoxicity.
AB  - Prion diseases comprise a group of rapidly progressive and invariably fatal
      neurodegenerative disorders for which there are no effective treatments. While
      conversion of the cellular prion protein (PrP(C)) to a beta-sheet rich isoform
      (PrP(Sc) ) is known to be a critical event in propagation of infectious prions,
      the identity of the neurotoxic form of PrP and its mechanism of action remain
      unclear. Insights into this mechanism have been provided by studying PrP
      molecules harboring deletions and point mutations in the conserved central
      region, encompassing residues 105-125. When expressed in transgenic mice, PrP
      deleted for these residues (Delta105-125) causes a spontaneous neurodegenerative
      illness that is reversed by co-expression of wild-type PrP. In cultured cells,
      Delta105-125 PrP confers hypersensitivity to certain cationic antibiotics and
      induces spontaneous ion channel activity that can be recorded by
      electrophysiological techniques. We have utilized these drug-hypersensitization
      and current-inducing activities to identify which PrP domains and subcellular
      locations are required for toxicity. We present an ion channel model for the
      toxicity of Delta105-125 PrP and related mutants and speculate how a similar
      mechanism could mediate PrP(Sc)-associated toxicity. Therapeutic regimens
      designed to inhibit prion-induced toxicity, as well as formation of PrP(Sc) , may
      prove to be the most clinically beneficial.

PMID- 22453178
TI  - Comparative peptidome analyses of the profiles of the peptides ranging from 1-10
      KD in CSF samples pooled from probable sporadic CJD and non-CJD patients.
AB  - The shotgun strategy applying tandem mass spectrometry has been widely used to
      identify the proteins that are differentially distributed among diseases for its
      high reliability and efficiency. To find out the potential difference of protein
      profiles in cerebrospinal fluids (CSF) between Creutzfeldt-Jakob disease (CJD)
      and non-CJD patients, especially in the fraction ranging from 1-10 KD, the CSF
      samples of 40 probable sporadic CJD (sCJD) patients, 32 non-CJD cases with
      dementia and 17 non-CJD cases without dementia were separately pooled and
      enriched by the magnetic beads based weak cation exchange chromatography (MB
      WCX). After trypsin digestion, each enriched CSF was separated and identified by
      RP-HPLC-ESI-QTOF MS/MS. In total, 42, 53 and 47 signals of proteins were
      identified in the pooled CSF fraction less than 10 KD of probable sCJD, non-CJD
      with dementia and non-CJD without dementia, respectively. Compared with that of
      probable sCJD, the similarity of CSF protein profiles of non-CJD with dementia
      (76.2%) were higher than that of non-CJD without dementia (57.1%). Nine CSF
      proteins were found to be specially observed in probable sCJD group. Those data
      may help to select the potential biomarkers for diagnosis of CJD. Additionally,
      further studies of the small segments of cellular proteins in CSF of CJD patients
      may also provide scientific clues for understanding the neuropathogenesis of
      TSEs.

PMID- 22453179
TI  - Salivary prions in sheep and deer.
AB  - Scrapie of sheep and chronic wasting disease (CWD) of cervids are transmissible
      prion diseases. Milk and placenta have been identified as sources of scrapie
      prions but do not explain horizontal transmission. In contrast, CWD prions have
      been reported in saliva, urine and feces, which are thought to be responsible for
      horizontal transmission. While the titers of CWD prions have been measured in
      feces, levels in saliva or urine are unknown. Because sheep produce ~17 L/day of
      saliva, and scrapie prions are present in tongue and salivary glands of infected
      sheep, we asked if scrapie prions are shed in saliva. We inoculated transgenic
      (Tg) mice expressing ovine prion protein, Tg(OvPrP) mice, with saliva from seven
      Cheviot sheep with scrapie. Six of seven samples transmitted prions to Tg(OvPrP)
      mice with titers of -0.5 to 1.7 log ID50 U/ml. Similarly, inoculation of saliva
      samples from two mule deer with CWD transmitted prions to Tg(ElkPrP) mice with
      titers of -1.1 to -0.4 log ID50 U/ml. Assuming similar shedding kinetics for
      salivary prions as those for fecal prions of deer, we estimated the secreted
      salivary prion dose over a 10-mo period to be as high as 8.4 log ID50 units for
      sheep and 7.0 log ID50 units for deer. These estimates are similar to 7.9 log
      ID50 units of fecal CWD prions for deer. Because saliva is mostly swallowed,
      salivary prions may reinfect tissues of the gastrointestinal tract and contribute
      to fecal prion shedding. Salivary prions shed into the environment provide an
      additional mechanism for horizontal prion transmission.

PMID- 22453180
TI  - Therapeutic effect of CHF5074, a new gamma-secretase modulator, in a mouse model
      of scrapie.
AB  - In Transmissible Spongiform Encephalopathies (TSEs) and Alzheimer disease (AD)
      both misfolding and aggregation of specific proteins represent key features.
      Recently, it was observed that PrP (c)  is a mediator of a synaptic dysfunction
      induced by Abeta oligomers. We tested a novel gamma secretase modulator (CHF5074)
      in a murine model of prion disease. Groups of female mice were intracerebrally or
      intraperitoneally infected with the mouse-adapted Rocky Mountain Laboratory
      prions. Two weeks prior infection, the animals were provided with a CHF5074
      medicated diet (375 ppm) or a standard diet (vehicle) until they showed
      neurological signs and eventually died. In intracerebrally infected mice, oral
      administration of CHF5074 did not prolong survival of the animals. In
      intraperitoneally-infected mice, CHF5074-treated animals showed a median survival
      time of 21 days longer than vehicle-treated mice (p < 0.001). In these animals,
      immunohistochemistry analyses showed that deposition of PrP (Sc)  in the
      cerebellum, hippocampus and parietal cortex in CHF5074-treated mice was
      significantly lower than in vehicle-treated animals. Immunostaining of glial
      fibrillary acidic protein (GFAP) in parietal cortex revealed a significantly
      higher reactive gliosis in CHF5074-treated mice compared to the control group of
      infected animals. Although the mechanism underlying the beneficial effects of
      CHF5074 in this murine model of human prion disease is unclear, it could be
      hypothesized that the drug counteracts PrP (Sc ) toxicity through astrocyte
      mediated neuroprotection. CHF5074 shows a pharmacological potential in murine
      models of both AD and TSEs thus suggesting a link between these degenerative
      pathologies.

PMID- 22453181
TI  - PRND 3'UTR polymorphism may be associated with behavioral disturbances in
      Alzheimer disease.
AB  - The etiology of behavioral and psychological symptoms of dementia (BPSD) is
      complex, including putative biological, psychological, social and environmental
      factors. Recent years have witnessed accumulation of data on the association
      between genetic factors and behavioral abnormalities in Alzheimer disease (AD).
      In this research paper, our aim is to evaluate the association between the APOE,
      CYP46, PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish
      subjects with AD and mild cognitive impairment (MCI). We studied 99 patients with
      AD and 48 subjects with MCI. The presence and profile of BPSD were evaluated at
      baseline and prospectively with the Neuropsychiatric Inventory (NPI). Patients
      were dichotomized into those having ever experienced a particular symptom and
      those who did not over the whole disease period. Genotyping was performed using
      previously described standard protocols. The prevalence of comorbid behavioral
      symptoms and the overall level of behavioral burden were significantly greater in
      AD compared with the MCI group. In AD patients, carrier status of the T allele of
      the 3'UTR (untranslated region) PRND polymorphism was associated with an
      increased cumulative behavioral load and an elevated risk for delusions, anxiety,
      agitation/aggression, apathy and irritability/emotional ability. Among MCI
      subjects, APOE epsilon4 carriers demonstrated a reduced risk for nighttime
      behavior change. No other statistically significant genotype-phenotype
      correlations were observed, including the APOE, CYP46 and PRNP genes. A precise
      estimation of the exact significance of particular polymorphisms in BPSD etiology
      requires future studies on large populations.

PMID- 22453182
TI  - Y145Stop is sufficient to induce de novo generation prions using protein
      misfolding cyclic amplification.
AB  - A point mutation in Prnp that converts tyrosine (Y) at position 145 into a stop
      codon leading to a truncated prion molecule as found in an inherited
      transmissible spongiform encephalopathy (TSE), Gertsmann-Straussler-Scheincker
      syndrome, suggests that the N-terminus of the molecule (spanning amino acids 23
      144) likely plays a critical role in prion misfolding as well as in protein
      protein interactions. We hypothesized that Y145Stop molecule represents an
      unstable part of the prion protein that is prone to spontaneous misfolding.
      Utilizing protein misfolding cyclic amplification (PMCA) we show that the
      recombinant polypeptide corresponding to the Y145Stop of sheep and deer PRNP can
      be in vitro converted to PK-resistant PrP (Sc)  in presence or absence of
      preexisting prions. In contrast, recombinant protein full-length PrP (C)  did not
      show a propensity for spontaneous conformational conversion to protease resistant
      isoforms. Further, we show that seeded or spontaneously misfolded Y145Stop
      molecules can efficiently convert purified mammalian PrP (C)  into protease
      resistant isoforms. These results establish that the N-terminus of PrP (C) 
      molecule corresponding to residues 23-144 plays a role in seeding and misfolding
      of mammalian prions.

PMID- 22453183
TI  - Comparative analysis of Japanese and foreign L-type BSE prions.
AB  - L-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE. To
      characterize the Japanese L-type BSE prion, we conducted a comparative study of
      the Japanese and foreign L-type BSE isolates. The L-type BSE isolates of Japan,
      Germany, France and Canada were intracerebrally inoculated into bovinized prion
      protein-overexpressing transgenic mice (TgBoPrP). All the examined L-type BSE
      isolates were transmitted to TgBoPrP mice, and no clear differences were observed
      in their biological and biochemical properties. Here, we present evidence that
      the Japanese and Canadian L-type BSE prions are identical to those from the
      European cases.

PMID- 22453185
TI  - Antimuscarinic drugs to treat overactive bladder.

PMID- 22453184
TI  - Discontinuation of hormone replacement therapy after myocardial infarction and
      short term risk of adverse cardiovascular events: nationwide cohort study.
AB  - OBJECTIVE: To assess the risk of adverse cardiovascular events in women who
      discontinue hormone replacement therapy after myocardial infarction compared with
      those who continue. DESIGN: Nationwide register based cohort study. SETTING: All
      hospitals in Denmark. POPULATION: All 3322 women aged 40 years or over who
      survived 30 days after a myocardial infarction and were prescribed hormone
      replacement therapy at the time of myocardial infarction in the period 1997 to
      2008. MAIN OUTCOME MEASURES: Reinfarction, cardiovascular mortality, and all
      cause mortality 30 to 360 days after discharge.: RESULTS: A total of 282 (8.5%)
      women had a reinfarction, 218 (6.6%) died of cardiovascular causes, and 357
      (10.7%) died of any cause during follow-up. Women who discontinued overall
      hormone replacement therapy in the first year after myocardial infarction did not
      have a significantly different risk of reinfarction (hazard ratio 0.90, 95%
      confidence interval 0.68 to 1.19), cardiovascular mortality (1.21, 0.90 to 1.62),
      or all cause mortality (1.22, 0.97 to 1.53) than women who continued use.
      However, discontinuation of vaginal oestrogen was associated with a lower risk of
      reinfarction (hazard ratio 0.54, 0.34 to 0.86). CONCLUSION: No certain
      conclusions can be drawn regarding increased or decreased risk of adverse
      cardiovascular events with continuing hormone replacement therapy after
      myocardial infarction. The results rule out neither a modest benefit nor a
      worrisome increase in risk. These figures may be valuable when a possible
      cardiovascular risk of hormone replacement therapy needs to be balanced with
      menopausal symptoms for the individual patient.

PMID- 22453186
TI  - Joined-up working: introducing the best teams of the year.

PMID- 22453187
TI  - Cameron launches challenge to end "national crisis" of poor dementia care.

PMID- 22453188
TI  - US travellers to the London Olympics are warned about contracting measles.

PMID- 22453189
TI  - Taurine and glutathione levels in plasma before and after ECT treatment.
AB  - Taurine has been shown to be elevated in plasma and lymphocytes of depressed
      patients, but the level normalises after successful drug therapy. During
      depression, levels of glutathione (GSH) are decreased in the plasma and blood.
      This study was performed to examine taurine and GSH levels in depressed patients
      before and after electroconvulsive therapy (ECT). Fasting blood samples were
      collected from 23 patients before the first and after the third ECT treatment.
      The severity of depression was estimated with the Montgomery-Asberg Depression
      Rating Scale (MADRS). We analysed GSH in blood and the levels of taurine and
      total GSH in plasma. After three ECTs, a significant decrease in MADRS scores was
      found for the entire group. Simultaneously, the decrease in the plasma taurine
      levels was significant for the seven responders but not for the sixteen non
      responders. We observed no differences in blood or plasma GSH levels after three
      ECT treatments when compared to values before the therapy. Plasma taurine levels
      decrease significantly after three ECT treatments in patients who respond to
      treatment. GSH levels were not affected by ECT treatment. The results indicate
      that taurine may play a role in the pathophysiology of depression.

PMID- 22453190
TI  - Clinical pharmacology and orphan drugs: an informational inventory 2006-2010.
AB  - Clinical pharmacology can have an important impact on the development of orphan
      drugs, i.e., therapeutic agents for rare diseases. This topic was explored at a
      US Food and Drug Administration (FDA) Advisory Committee meeting in March 2011.1
      At that meeting, preliminary data were presented regarding the breakdown of the
      clinical pharmacology content in the approvals for orphan drugs in 2006
      2010.These data, along with follow-up observations, are presented here, focusing
      on the in vivo study content and the relevant populations.

PMID- 22453191
TI  - Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by
      quantitative EEG in healthy volunteers.
AB  - The pharmacokinetics and pharmacodynamics of a highly concentrated cyclodextrin
      based intranasal (i.n.) midazolam formulation containing the absorption-enhancer
      chitosan were studied in 12 healthy volunteers and compared with intravenous
      (i.v.) midazolam. The pharmacodynamic (PD) effects were assessed using
      quantitative electroencephalography (EEG). Maximal plasma concentrations of 63
      and 110 ng/ml were reached at 8.4 and 7.6 min after 3 and 6 mg i.n. midazolam,
      respectively. After 5 mg i.v. and 6 and 3 mg i.n. midazolam, the times to onset
      of significant EEG effects in the beta2 band (18-25 Hz) were 1.2, 5.5, and 6.9
      min, respectively, and the times to loss of response to auditory stimuli were
      3.0, 8.0, and 15.0 min, respectively. A sigmoid maximum-effect (E(max)) model
      indicated disequilibrium between plasma and effect-site concentrations, with
      equilibration half-lives of 2.1-4.8 min. The observed pharmacokinetic-PD (PK-PD)
      properties suggest that i.n. midazolam deserves to be evaluated as an easy and
      noninvasive method of administering a first benzodiazepine dose, e.g., in out-of
      hospital emergency settings with no immediate i.v. access.

PMID- 22453192
TI  - Safety learning from drugs of the same class: room for improvement.
AB  - This study was aimed at assessing the extent of safety learning from data
      pertaining to other drugs of the same class. We studied drug classes for which
      the first and second drugs were centrally registered in the European Union from
      1995 to 2008. We assessed whether adverse drug reactions (ADRs) associated with
      one of the drugs also appeared in the Summary of Product Characteristics (SPC) of
      the other drug, either initially or during the postmarketing phase. We identified
      977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of
      both drugs of a pair. Of these 393 that were present in both SPCs of a drug pair,
      241 (61.3%) were present when the drug entered the market and 152 (30.7%)
      appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same
      class drugs in the postmarketing phase was associated with type A ADRs, marketing
      in the same regulator country, a longer time interval between entry into the
      market by the two drugs, and an earlier date of ADR. Although there appears to be
      some degree of safety learning from same-class drugs, there is still room for
      improvement, possibly by increasing proactive risk management.

PMID- 22453193
TI  - Human pregnane X receptor genotype of the donor but not of the recipient is a
      risk factor for delayed graft function after renal transplantation.
AB  - Delayed graft function (DGF) is an important complication in renal
      transplantation, contributing significantly to decrease in long-term allograft
      survival. In addition to donor- and recipient-related risk factors such as
      immunosuppression, altered renal excretion of xenobiotics by membrane
      transporters may influence DGF. Using DNA samples from recipients and donors, we
      assessed the impact on DGF of genetic variants in P-glycoprotein (ABCB1),
      multidrug resistance protein 2 (ABCC2), and the nuclear pregnane X receptor
      (PXR/NR1I2), which regulates the transcription of enzymes and transporters. In
      our local cohort of renal transplant recipients (n = 178), DGF occurred in 27.5%.
      The PXR 8055TT genotype of the donor only (not of the recipient) was
      significantly associated with an increased risk for DGF. This finding emerged
      from univariate as well as multivariate logistic regression analysis including 16
      nongenetic factors and held true after correction for multiple testing. Our
      findings provide the first evidence that PXR may be associated with risk of DGF,
      independent of previously identified risk factors.

PMID- 22453194
TI  - A risk-benefit assessment of prasugrel, clopidogrel, and genotype-guided therapy
      in patients undergoing percutaneous coronary intervention.
AB  - The objective of this study was to quantitatively evaluate the clinical benefits
      and harms of prasugrel, clopidogrel, and a CYP2C19 genotype-guided drug selection
      strategy for patients with acute coronary syndrome (ACS) and planned percutaneous
      coronary intervention (PCI). We used decision-analytic techniques to model the
      risks and benefits of alternative antiplatelet strategies. Sensitivity and
      scenario analyses were conducted to assess the uncertainty of the results.
      Prasugrel demonstrated little difference in net benefit as compared with
      clopidogrel (+0.02 quality-adjusted life-years (QALYs); 95% confidence range
      (CR), -0.23 to 0.21). The genotype-guided strategy had a 93% probability of
      greater net benefit as compared with clopidogrel (+0.05 QALYs; 95% CR, -0.02 to
      0.11), and 66% probability of greater net benefit as compared with prasugrel
      (+0.03 QALYs; 95% CR, -0.13 to 0.24). Prasugrel and clopidogrel differ in their
      risk-benefit profiles but appear to offer similar net benefit on average. Use of
      patient-specific factors such as CYP2C19 genotype offers promise for developing a
      personalized medicine approach to antiplatelet treatment regimens.

PMID- 22453195
TI  - Influence of pharmacy benefit practices on off-label dispensing of drugs in the
      United States.

PMID- 22453197
TI  - Spindle in position for symmetric division.

PMID- 22453196
TI  - Sildenafil increases digital skin blood flow during all phases of local cooling
      in primary Raynaud's phenomenon.
AB  - Digital skin vasoconstriction on local cooling is exaggerated in primary
      Raynaud's phenomenon (RP) as compared with controls. A significant part of such
      vasoconstriction relies on the inhibition of the nitric oxide (NO) pathway. We
      tested the effect of the phosphodiesterase 5 (PDE5) inhibitor sildenafil, which
      potentiates the effect of NO, on skin blood flow. We recruited 15 patients with
      primary RP, performing local cooling without sildenafil (day 1), after a single
      oral dose of 50 mg (day 2), and after a dose of 100 mg (day 3). Skin blood flow,
      skin temperature, and arterial pressure were recorded, and data were expressed as
      cutaneous vascular conductance (CVC). Sildenafil at 100 mg, but not 50 mg,
      significantly lessened the cooling-induced decrease in CVC. It also increased
      resting CVC and skin temperature. These data suggest that 100 mg sildenafil
      improves digital skin perfusion during local cooling in primary RP. The benefit
      of sildenafil "as required" should be confirmed in a randomized, controlled
      trial.

PMID- 22453198
TI  - Risks and benefits of menopausal hormone therapy in postmenopausal Chinese women.
AB  - OBJECTIVE: The aim of this study was to assess risks and benefits of conjugated
      equine estrogens (CEE) and medroxyprogesterone acetate (MPA) in postmenopausal
      Chinese women. METHODS: A retrospective cohort study was undertaken using the
      Taiwan National Health Insurance Research Database, a population-based healthcare
      claims dataset. Eligible women aged 50 to 79 years were classified as exposed to
      CEE 0.625 mg/day with MPA 5.0 mg/day (estrogen [E] + progestin [P], n = 4,712) or
      CEE 0.625 mg/day only (E-only, n = 1,208) and were age-matched to unexposed women
      (n = 10,125). Follow-up was complete in 96% of the participants. The primary
      outcomes were coronary heart disease (CHD) and invasive breast cancer. The global
      index summarized risks of primary outcomes, stroke, pulmonary embolism, colon and
      endometrial cancers, hip fractures, and death. Time-to-event analyses were
      performed. RESULTS: Median durations of exposure in the E + P and E-only groups
      were 6.9 and 9 months, respectively. Median follow-up was 110 months. Hazard
      ratios (95% CI) for E + P exposure were as follows: myocardial infarction, 0.78
      (0.51-1.19); CHD death, 1.21 (0.53-2.70); breast cancer, 1.48 (1.20-1.83); global
      index, 0.79 (0.72-0.87). Hazard ratios for E-only exposure were as follows:
      myocardial infarction, 0.76 (0.35-1.68); CHD death, 0.57 (0.11-2.80); breast
      cancer, 1.44 (0.99-2.10); global index, 1.09 (0.92-1.28). Per 10,000 person
      years, there were 12 excess breast cancer cases with E + P exposure; there were
      39 fewer global index events with E + P exposure. Adjusting for age, statin and
      aspirin use, hypercholesterolemia, diabetes, and hypertension did not
      significantly change estimates. CONCLUSIONS: In postmenopausal Chinese women, CEE
      with or without MPA was not associated with increased rates of CHD, but CEE with
      MPA may be associated with a higher breast cancer rate. E + P exposure conferred
      lower global index event rates.

PMID- 22453199
TI  - Cross-cultural adaptation and validation of the Falls Efficacy Scale
      International in Spanish postmenopausal women.
AB  - OBJECTIVE: Falls are a serious public health problem and one of the most
      important concerns for older people. The risk of falling is dramatically
      increased in osteoporotic postmenopausal women. The Falls Efficacy Scale
      International (FES-I) is a reliable and validated questionnaire that can assess
      the fear of falling. Our objective is to develop the FES-I cross-cultural
      adaptation to the Spanish postmenopausal population. METHODS: FES-I was
      translated into Spanish language. One hundred postmenopausal women (50-65 years
      old) completed the FES-I and the 36-item Short-Form Health Survey (SF-36)
      questionnaire. Content validity was determined by a group of experts and
      participants. FES-I internal consistency and test-retest reliability were
      analyzed. Exploratory factor analysis was used to assess construct validity.
      Criterion validity has been evaluated using the Spearman correlation coefficient
      with the 36-item Short-Form Health Survey. RESULTS: FES-I has an excellent test
      retest reliability (intraclass correlation coefficient, 0.972; P < 0.001) and
      good internal consistency (Cronbach alpha = 0.940). Factor analysis showed one
      unifactorial structure with two underlying dimensions related to less or more
      demanding physical activities. FES-I global score showed a negative correlation
      with the two SF-36 summary measures (P < 0.001). CONCLUSIONS: The Spanish version
      of FES-I showed high reliability and validity in the adaptation for the Spanish
      postmenopausal population. Future studies are required to assess the sensitivity
      to change and to predict the risk of future falling.

PMID- 22453200
TI  - Oral micronized progesterone for vasomotor symptoms--a placebo-controlled
      randomized trial in healthy postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to compare oral micronized progesterone
      (progesterone) with placebo as therapy for postmenopausal hot flushes and night
      sweats (vasomotor symptoms [VMS]). METHODS: Healthy volunteer community women 1
      to 10 years since final menstruation were recruited for a randomized double-blind
      placebo-controlled trial of progesterone (300 mg daily at bedtime) between 2003
      and 2009 and were screened for clinical, physical, or laboratory evidence of
      cardiovascular risks (nonsmoking, moderate body mass index [<35 kg/m], normal
      lipids, electrocardiogram, nondiabetic). Women recorded daily frequency and
      severity (1-4) of VMS in the Daily Menopause Diary during run-in (4 wk) and
      intervention (12 wk). Average daily VMS score (day frequency * day severity +
      night frequency * night severity) during final 28 therapy days was the primary
      outcome, analyzed by therapy, with run-in score as covariate. RESULTS: Randomized
      participants were 133 healthy community women with VMS, ages 44 to 62 years, with
      a mean (SD) VMS score of 17.0 (10.4) at run-in (VMS frequency 6.8 [3.2]
      episodes/d). Women were randomized to progesterone (n = 75) or placebo (n = 58);
      analysis included all with VMS data at run-in and on therapy (n = 68 and 46,
      respectively). The VMS scores of women taking progesterone were better than
      placebo (mean adjusted difference, -4.3 (95% CI, -6.6 to -1.9), with mean
      reductions of 10.0 (95% CI, -12.0 to -8.1) and 4.4 (95% CI, -6.6 to -2.2) in the
      progesterone and placebo arms, respectively. Discontinuation with adverse events
      was 9% (progesterone, 8; placebo, 4), with no serious cases. CONCLUSIONS: Oral
      micronized progesterone is effective for treatment of hot flushes and night
      sweats in healthy women early in postmenopause.

PMID- 22453201
TI  - Is there any reason to suspect that the determinants of mandibular bone mineral
      density might differ from those of systemic skeletal bone mineral density?

PMID- 22453202
TI  - MR-guided focused ultrasound for the treatment of uterine fibroids.
AB  - Magnetic resonance imaging-guided focused ultrasound (MRgFUS) ablation of uterine
      fibroids provides a minimally invasive outpatient technique for targeting and
      treating symptomatic uterine fibroids. Magnetic resonance imaging provides a
      guidance platform that has high temporal and spatial resolution for guiding, as
      well as thermal monitoring of the procedure. The high-intensity focused
      ultrasound provides a mechanism for delivering large amounts of energy directly
      into the fibroid without causing detrimental effects to the nontarget tissues.
      Early and intermediate follow-up of patients treated with MRgFUS provided
      promising results on the efficacy of the technique for providing symptom relief
      to patients. As more long-term follow-up data are published, the efficacy of this
      technique can be compared to more invasive surgical and minimally invasive
      catheter treatments.

PMID- 22453203
TI  - Cationic polymers and aptamers mediated aggregation of gold nanoparticles for the
      colorimetric detection of arsenic(III) in aqueous solution.
AB  - As(III) specifically interacts with an arsenic-binding aptamer to form an As(III)
      aptamer complex, so that the following cationic polymer can aggregate gold
      nanoparticles (AuNPs) and cause a remarkable change in color, which enables the
      colorimetric detection of As(III) with high selectivity and a detection limit of
      5.3 ppb.

PMID- 22453204
TI  - Calcium imaging of odor-evoked responses in the Drosophila antennal lobe.
AB  - The antennal lobe is the primary olfactory center in the insect brain and
      represents the anatomical and functional equivalent of the vertebrate olfactory
      bulb. Olfactory information in the external world is transmitted to the antennal
      lobe by olfactory sensory neurons (OSNs), which segregate to distinct regions of
      neuropil called glomeruli according to the specific olfactory receptor they
      express. Here, OSN axons synapse with both local interneurons (LNs), whose
      processes can innervate many different glomeruli, and projection neurons (PNs),
      which convey olfactory information to higher olfactory brain regions. Optical
      imaging of the activity of OSNs, LNs and PNs in the antennal lobe - traditionally
      using synthetic calcium indicators (e.g. calcium green, FURA-2) or voltage
      sensitive dyes (e.g. RH414) - has long been an important technique to understand
      how olfactory stimuli are represented as spatial and temporal patterns of
      glomerular activity in many species of insects. Development of genetically
      encoded neural activity reporters, such as the fluorescent calcium indicators G
      CaMP and Cameleon, the bioluminescent calcium indicator GFP-aequorin, or a
      reporter of synaptic transmission, synapto-pHluorin has made the olfactory system
      of the fruitfly, Drosophila melanogaster, particularly accessible to
      neurophysiological imaging, complementing its comprehensively-described
      molecular, electrophysiological and neuroanatomical properties. These reporters
      can be selectively expressed via binary transcriptional control systems (e.g.
      GAL4/UAS, LexA/LexAop, Q system) in defined populations of neurons within the
      olfactory circuitry to dissect with high spatial and temporal resolution how odor
      evoked neural activity is represented, modulated and transformed. Here we
      describe the preparation and analysis methods to measure odor-evoked responses in
      the Drosophila antennal lobe using G-CaMP. The animal preparation is minimally
      invasive and can be adapted to imaging using wide-field fluorescence, confocal
      and two-photon microscopes.

PMID- 22453205
TI  - Workplace bullying, working environment and health.
AB  - Improved work organisation could be of importance for decreased bullying in
      workplaces. Participants in the Swedish Longitudinal Occupational Survey of
      Health (SLOSH) responded to questions about work and workplace and whether they
      had been bullied during the past year in 2006. Those in worksites with at least
      five employees who did not report that they had been bullied in 2006 and without
      workplace change between 2006 and 2008 constituted the final sample (n=1,021 men
      and 1,182 women). Work characteristics and workplace factors in 2006 were used in
      multiple logistic regression as predictors of bullying in 2008. Separate analyses
      were performed for work characteristics and workplace factors respectively.
      Adjustments for demographic factors were made in all analyses. The question used
      for bullying was: "Are you exposed to personal persecution by means of vicious
      words or actions from your superiors or your workmates?" Such persecution any
      time during the past year was defined as bullying. For both genders
      organisational change and conflicting demands were identified as risk factors,
      and good decision authority as a protective factor. Dictatorial leadership, lack
      of procedural justice and attitude of expendability were male and lack of
      humanity a female risk factor for bullying.

PMID- 22453206
TI  - The relationship between flow, sleepiness and cognitive performance: the effects
      of short afternoon nap and bright light exposure.
AB  - "Flow" is a positive emotional state which typically occurs when a person
      perceives a balance between the challenges associated with a situation and his or
      her capabilities to accomplish these demands. While flow often occurs along with
      positive feelings and high introspective performance, only a few studies have
      investigated how it is associated with cognitive performance (i.e., objective
      performance). In the present study, we investigated the relationship between
      flow, emotions, and cognitive performance. A short nap (20 min) and bright light
      (>2,000 lux) techniques were used as experimental manipulations to enhance flow.
      Fifteen participants (31.3 +/- 7.19 yr old) took part in four experimental
      conditions: rest, short nap, bright light, and nap and bright light. Pearson's
      correlation coefficients were calculated for flow and other indices using
      standardized data. Results showed that flow scores significantly increased after
      a short nap and under bright light exposure. The correlations between flow and
      reaction time were also significant. Flow was significantly associated with
      positive emotion and sleepiness. These results suggest that a short nap and
      bright light can be employed as a flow facilitator and that flow status can be
      used as an indicator in evaluating work efficiency and occupational mental
      health.

PMID- 22453207
TI  - Future trends of mesothelioma mortality in Japan based on a risk function.
AB  - Mesothelioma is a malignancy with poor prognosis. It is chiefly caused by
      asbestos exposure and its symptoms can occur about 30-50 yr after the initial
      exposure. This study aims to predict the future trends in mesothelioma mortality
      in Japan using a method that is an alternative to the age-cohort model. Our
      approach is based on a risk function that links mesothelioma mortality combined
      with data pertaining to the population, size of the labor force, and quantity of
      asbestos imports. We projected the number of deaths occurring in individuals aged
      50-89 for yr 2003-2050 using risk functions. Our results have indicated that
      mesothelioma mortality among Japanese people aged 50-89 yr will continue to
      increase until 2027 and reach a maximum of 66,327 deaths in the years 2003-2050.
      Our estimate has also suggested that the number of mesothelioma deaths could be
      significantly reduced if there were adequate compliance with the administrative
      level guidelines for occupational asbestos exposure.

PMID- 22453208
TI  - Effect of exposure to occupational noise and shift working on blood pressure in
      rubber manufacturing company workers.
AB  - This study aimed to assess the relationship between shift working and
      occupational exposure to noise with blood pressure (BP). The study was carried
      out in a rubber manufacturing company in 2010. Demographic, medical and
      occupational information for carrying out the study were collected through direct
      interview. All 331 under study workers were divided into four groups according to
      work shift and noise exposure severity, from non-noise exposed day time workers
      (Group 1) to noise exposed shift workers (Group 4). Finally, systolic and
      diastolic blood pressure levels were compared among these four groups. The
      results of this study showed that there was a significant difference between
      average systolic and diastolic BP and hypertension (HTN) frequency in the four
      groups (p<0.05). The highest rate of HTN and mean systolic and diastolic BP were
      observed among shift workers who were exposed to noise higher than permissible
      limit (Group 4). Also the results of logistic regression analysis showed that
      there was a significant relationship between simultaneous exposures to noise more
      than the permitted limit and shift work with HTN (p<0.05). The results of our
      study showed that shift working and simultaneous exposure to noise have an
      additive effect on occurrence of HTN. It is recommended that during periodic
      physical examinations of noise exposed shift workers, assessment of the
      cardiovascular system and BP should be done as well as the auditory system.

PMID- 22453209
TI  - Dust exposure and respiratory symptoms among cement factory workers in the United
      Arab Emirates.
AB  - This study was conducted in a cement factory in the United Arab Emirates to
      assess cement dust exposure and its relationship to respiratory symptoms among
      workers. A total of 149 exposed and 78 unexposed workers participated in this
      cross-sectional study. Information on demographic and respiratory symptoms was
      collected by questionnaire. Personal total dust levels were determined by the
      gravimetric method. Concentration of the total dust ranged between 4.20 mg/m(3)
      in the crushers and 15.20 mg/m(3) in the packaging areas, and exceeded the
      exposure limit in the packaging and raw mill areas. The prevalence of respiratory
      symptoms was higher among the exposed workers, but the difference from that of
      unexposed workers was statistically significant only for cough (19.5%; OR=4.5;
      95%CI=1.5-13.2), and phlegm (14.8%; OR=13.3; 95%CI=1.8-100.9). Cough and phlegm
      were found to be related to exposure to dust, cumulative dust and smoking habit,
      while chronic bronchitis was related to smoking habit. The few factory workers
      (19.5%) who used masks all the time had a lower prevalence rate of respiratory
      symptoms than those not using them. High dust level was the only variable that
      influenced the workers to use the mask all the time. It is recommended that
      control measures be adopted to reduce the dust and workers should be encouraged
      to use respiratory protection devices during their working time.

PMID- 22453210
TI  - Precarious employment and health: analysis of the Comprehensive National Survey
      in Japan.
AB  - Recent studies suggest that unstable employment contracts may affect the health
      of workers. Many Japanese workers working full time in ostensibly permanent
      positions actually operate within unstable and precarious employment conditions.
      We compared the health status of Japanese workers with precarious employment
      contracts with that of permanent workers using the 2007 Comprehensive Survey of
      Living Conditions of the People on Health and Welfare (n=205,994). We classified
      their employment status as 'permanent' vs. 'precarious' (part-time, dispatch, or
      contract/non-regular) and compared their health conditions. Among both sexes,
      precarious workers were more likely than permanent workers to have poor self
      rated health or more subjective symptoms, with more workers in full-time
      employment suffering from serious psychological distress (SPD) and more female
      workers who smoke. Using logistic regression, we identified a positive
      association between precarious employment and SPD and current smoking among
      workers engaged in full-time employment after adjusting for age, marital status,
      and work-related conditions. This study demonstrates that precarious employment
      contracts are associated with poor self-rated health, psychological distress, and
      tobacco use, especially among people working full-time jobs. These results
      suggest that engagement in full-time work under unstable employment status
      impairs workers' health.

PMID- 22453212
TI  - Can workers answer their questions about occupational safety and health:
      challenges and solutions.
AB  - Many workers have questions about occupational safety and health (OSH). Answers
      to these questions empower them to further improve their knowledge about OSH,
      make good decisions about OSH matters and improve OSH practice when necessary.
      Nevertheless, many workers fail to find the answers to their questions. This
      paper explores the challenges workers may face when seeking answers to their OSH
      questions. Findings suggest that many workers may lack the skills, experience or
      motivation to formulate an answerable question, seek and find information,
      appraise information, compose correct answers and apply information in OSH
      practice. Simultaneously, OSH knowledge infrastructures often insufficiently
      support workers in answering their OSH questions. This paper discusses several
      potentially attractive strategies for developing and improving OSH knowledge
      infrastructures: 1) providing courses that teach workers to ask answerable
      questions and to train them to find, appraise and apply information, 2)
      developing information and communication technology tools or facilities that
      support workers as they complete one or more stages in the process from question
      to answer and 3) tailoring information and implementation strategies to the
      workers' needs and context to ensure that the information can be applied to OSH
      practice more easily.

PMID- 22453213
TI  - Enhancement of the electrocapacitive performance of manganese dioxide by
      introducing a microporous carbon spheres network.
AB  - An amorphous MnO(2).nH(2)O/microporous carbon spheres (alpha-MnO(2).nH(2)O/MCS)
      composite electrode material is prepared by a chemical co-precipitation method.
      It is observed that the amorphous MnO(2) particles are deposited on the surface
      of the MCS, which form a network with a uniquely developed three-dimensional open
      porous system containing macropores, mesopores and micropores. The
      electrochemical measurements reveal that the composite electrode material
      presents a much more stable and reversible capacitance behavior compared to the
      pure alpha-MnO(2).nH(2)O in 1 M of Na(2)SO(4) electrolyte. The composite
      containing 25 wt% MCS exhibits optimal specific capacitance of 218.2 F g(-1) at 2
      mV s(-1), and is still as high as 112.4 F g(-1) at 100 mV s(-1), while a drastic
      reduction from 197.0 F g(-1) at 2 mV s(-1) to only 40.7 F g(-1) at 100 mV s(-1)
      occurs for the pure alpha-MnO(2).nH(2)O. The composite also shows a rather high
      electrode-specific capacitance of 3.13 F cm(-2) and a long cycle life. The
      remarkable enhancement in the electrochemical performance is mainly attributed to
      the microporous structure of the MCS contributing to the deposition of MnO(2)
      particles on the surface of the MCS, and the uniquely developed porous network of
      the composite facilitating the rapid transport of the electrolyte. These factors
      result in the high electrochemical utilization of MnO(2), a great reduction of
      the equivalent series resistance, and hence the relatively high and stable
      electrochemical behavior.

PMID- 22453215
TI  - Welcome from the president.

PMID- 22453219
TI  - Fellow lecture series.

PMID- 22453216
TI  - Editor's Introduction.

PMID- 22453220
TI  - Diagnosis and management of female urethral diverticulum.
AB  - Female urethral diverticulum is a disorder that affects 1% to 6% of women. Women
      with diverticula may present with a variety of nonspecific genitourinary
      complaints, making the diagnosis challenging. Diagnosis is made by physical
      examination and can be confirmed with cystourethroscopy and/or radiographic
      imaging. Asymptomatic women can be managed conservatively, whereas treatment for
      symptomatic women usually involves a diverticulectomy. Potential complications
      from diverticulectomy include diverticulum recurrence, de novo stress
      incontinence, urethrovaginal fistula, urethral stricture, and recurrent urinary
      tract infections. This article reviews the etiology, differential diagnoses,
      evaluation, and management of female urethral diverticula.

PMID- 22453214
TI  - Androgen action and metabolism in prostate cancer.
AB  - The transcriptional programs regulated through the activity of the androgen
      receptor (AR) modulate normal prostate development and the maintenance of
      prostatic functions at maturity. AR signaling also controls key survival and
      growth functions operative in prostate cancer. Inhibiting the AR program remains
      the key target in the treatment of advanced prostate cancer, and suppressing AR
      also holds great potential for preventing the development or progression of early
      stage prostate cancer. In this review, we detail molecular mechanisms of AR
      activity, cellular components contributing to the maintenance of AR signaling
      despite AR-ligand suppression, and discuss treatment strategies designed to
      target components of resistance to AR-directed therapeutics.

PMID- 22453221
TI  - Urinary tract infections.
AB  - Urinary tract infections (UTIs) are prevalent and an important topic for the
      urogynecologist. In this article, we review important definitions, the
      pathophysiology, and identifiable risk factors for UTI. In addition, the
      evaluation and management of UTIs is summarized. Finally, attention is focused on
      UTIs in special populations, including pregnant, hospitalized, and postoperative
      patients. The latest recommendations from the urologic, infectious disease,
      gynecologic, and systematic review literature are discussed.

PMID- 22453222
TI  - Bladder pain syndrome: a review.
AB  - OBJECTIVE: : Bladder pain syndrome (BPS), including the specific variant
      interstitial cystitis, is a chronic condition characterized by bladder, urethral,
      and pelvic pain; urinary urgency; and urinary frequency. Bladder pain syndrome
      poses many clinical challenges: (1) The diagnosis is one of exclusion and is
      often inappropriately assigned; (2) a wide-range spectrum of symptoms can be
      noted in the population from minimally affected to debilitated; and (3) the
      etiology for the disease is unknown, which has made the development of directed
      therapies problematic. The objective of this article was to review the current
      theories of etiology of BPS and the diagnosis of BPS and understand treatment
      options including surgical, complementary, and pharmaceutical.

PMID- 22453223
TI  - The prevalence of microscopic hematuria in women with pelvic organ prolapse.
AB  - OBJECTIVE: : The objective of the study was to determine the prevalence of
      microscopic hematuria (MH) in women with pelvic organ prolapse. STUDY DESIGN: :
      Data of all patients presenting to a urogynecologic center with pelvic organ
      prolapse between 2008 and 2010 were reviewed. Microscopic hematuria was defined
      as 3 or more red blood cells per high-power field on at least 2 urinalysis
      specimens with negative cultures. Exclusion criteria included age younger than 40
      years, presence of gross hematuria, menses, or urologic disease. Statistical
      analysis was performed using JMP 4.0.4 (SAS Institute, Cary, NC). RESULTS: : The
      population consisted of 572 women aged 40 to 96 years. Fifty-five patients (9.6%)
      met the criteria for MH, and 126 (22%) had 3 or more red blood cells per high
      power field on 1 urinalysis. No cases of urologic malignancy were diagnosed on
      further workup. All patients with microhematuria had cystoceles on examination.
      CONCLUSIONS: : Our findings suggest that the prevalence of MH is increased in
      women with pelvic organ prolapse.

PMID- 22453224
TI  - Percutaneous nerve evaluation in women: lessons learned.
AB  - OBJECTIVES: : The primary aim of this study was to identify patient
      characteristics potentially affecting response to office-based percutaneous nerve
      evaluation (PNE). Secondarily, we aimed to identify appropriate candidates to
      undergo office-based PNE. METHODS: : A retrospective chart review was conducted
      from 2000 to 2011 of female patients who underwent office-based PNE. Data were
      separated into 3 groups based on outcome: success, equivocal, and failure. Data
      examined included patient demographics, voiding dysfunction diagnosis,
      comorbidities, evidence of previous pelvic nerve injury, systemic hormonal
      status, and neurological insult of such varieties as stroke and Parkinson
      disease. All data were analyzed using chi analysis and analysis of variance. P <
      0.05 was considered statistically significant. RESULTS: : One hundred twelve
      women underwent office-based PNE. Seventy-four patients (66.1%) had a successful
      outcome, 15 (13.4%) had an equivocal outcome, and 23 patients (20.5%) failed PNE
      trial. Neurological insult was the only factor of significance identified in
      those patients with an equivocal or unsuccessful trial of office-based PNE. After
      categorizing body mass index according to the World Health Organization's 2011
      guidelines, no significance was found for body mass index between successful
      outcomes, equivocal outcomes, and failures. CONCLUSIONS: : Our cohort
      demonstrates that those patients who had an equivocal or failed outcome of office
      based PNE were more likely to have a neurological insult. Patients with
      neurological insult who are considered appropriate candidates for neuromodulation
      trial should undergo staged implantation with quadruple tined lead in the
      operating room to provide these patients with the greatest opportunity for
      successful outcome.

PMID- 22453225
TI  - Pessary use and impact on quality of life and body image.
AB  - OBJECTIVES: : The objective of the study was to determine if vaginal pessaries
      improve symptoms of prolapse and body image in women with pelvic organ prolapse.
      Our hypothesis was that pessary use would improve prolapse-related symptoms and
      body image up to 1 year. METHODS: : Women presenting for pessary insertion
      completed questionnaires regarding pelvic floor-related symptoms and body image
      with successful pessary insertion and after 6 to 12 months of continued pessary
      use. Scores were compared with a paired t test. RESULTS: : Forty-three subjects
      had complete data for analysis. Scores on both prolapse-related and body image
      questionnaires showed improvements at 6 months (P < 0.001) and 12 months (P <
      0.010). Younger women and those with prior prolapse surgery were less likely to
      continue to use a pessary past 3 to 6 months. Stage of prolapse, body mass index,
      and scores on symptom questionnaires did not correlate with likelihood of
      continued pessary use versus surgery. CONCLUSIONS: : The use of a pessary for
      more than 12 months improves symptoms of prolapse and self perception of body
      image.

PMID- 22453226
TI  - Slings may not fail as frequently as believed for stress urinary incontinence:
      the misinterpretation of postoperative voiding dysfunction as failure based on
      patient report.
AB  - OBJECTIVE: : Sling operations may obstruct the urethra, promoting voiding
      dysfunction and secondary urine leakage that are incorrectly attributed to
      surgical failure. METHODS: : We prospectively evaluated the evolution of urinary
      symptoms in the postoperative follow-up of 108 polypropylene sling cases.
      Patients presented for follow-up at 1, 3, 6, 12, 18, 24, 36, and 48 months for
      review of individual urinary symptoms. Statistical analysis used Fisher exact
      test. RESULTS: : On the 30th postoperative day, 100% of the cases were cured of
      stress urinary incontinence, although frequency (62.9%), urgency (29.6%), urge
      incontinence (23.1%), nocturia (28.6%), incomplete voiding sensation (11.1%), and
      poor stream (11.1%) persisted. At 3 months, 16.6% reported frequency, 38%
      complained of urgency, and 29.6% were troubled by nocturia. True urinary leakage
      under stress was resolved in 100% of cases by the first visit and did not show
      any further decrease when specifically questioned. Pad usage decreased after 3
      months but did not completely disappear after 48 months. A total of 94.4% of the
      cases achieved total continence and clinical satisfaction after 4 years of follow
      up, in parallel with the steady disappearance of voiding dysfunction observed in
      the early postoperative period. CONCLUSIONS: : Voiding dysfunction after sling
      procedures is frequent but transitory. As symptoms improve or disappear, patients
      tend to miss their follow-up. In this study, 94.4% of the cases had complete
      dryness and satisfaction with the operation.

PMID- 22453227
TI  - Determining health-related quality of life and health state utility values of
      urinary incontinence in women.
AB  - OBJECTIVES: : Health-related quality-of-life estimates currently available for
      urinary incontinence have largely been derived from population-based studies
      without physician confirmation of diagnosis. The purpose of this study was to
      compare the health state utility values for urinary incontinence in women derived
      from EQ-5D questionnaires and visual analog scale (VAS) with the economic gold
      standard method, the Standard Gamble (SG) interview. METHODS: : Subjects were
      approached for study participation after a diagnosis of stress or urge urinary
      incontinence was made by the attending urogynecologist. Twenty-eight patients
      completed the Sandvik Severity Index (SSI), EQ-5D, and VAS. They then
      participated in the SG conversation. RESULTS: : The median utility (interquartile
      range) for stress incontinence varied based on the methods: EQ-5D, 0.83 (0.23);
      VAS, 0.85 (0.15); and SG, 1.00 (0.01). There was a statistically significant
      difference between the SG assessment and the other 2 methods of assessing utility
      values, the EQ-5D and VAS in women with urodynamically demonstrated stress
      urinary incontinence (P = 0.0003 and P < 0.0001, respectively). In the combined
      group of women with urodynamically proven stress, urge, and mixed urinary
      incontinence, there was also a statistically significant difference between the
      SG and the generic methods of assessing utility values, the EQ-5D and VAS (P <
      0.0001). Mean SSI scores were similar in women with stress incontinence (6.6
      [23.5]) and in the combined group (7.9 [3.8]). CONCLUSIONS: : Previous studies
      may have underestimated the health-related quality of life of urinary
      incontinence.

PMID- 22453228
TI  - Hypnotherapy for treatment of overactive bladder: a randomized controlled trial
      pilot study.
AB  - OBJECTIVES: : The objective of the study was to obtain pilot data comparing
      hypnotherapy and behavioral therapy (hypnotherapy) to behavioral therapy alone
      (behavioral therapy) in overactive bladder (OAB) treatment. METHODS: : Women with
      OAB were randomized to hypnotherapy or behavioral therapy treatments. Patient
      Global Impression of Improvement (PGI-I), the OAB-q Short Form (OAB-q SF)
      questionnaire, and voiding diaries were recorded, and within- and between-group
      differences were compared. RESULTS: : Twenty women enrolled in and completed the
      study. Both hypnotherapy and behavioral therapy groups improved their mean number
      of voids (P = 0.005, P = 0.01, respectively) and their OAB-q SF distress scores
      (P = 0.002, P = 0.03). The hypnotherapy group had significant improvement in
      quality-of-life scores (P < 0.001), whereas the behavioral group did not (P =
      0.05). Between-group comparisons showed that the hypnotherapy group had superior
      PGI-I scores compared with the behavioral group (P < 0.009). The hypnotherapy
      group trended toward greater improvement in OAB-q quality-of-life scores compared
      with the behavioral therapy group (67% vs 42% improvement), although this did not
      reach statistical significance (P = 0.07). Number of voids and OAB-q SF distress
      scores improved in both groups with no difference between groups. CONCLUSIONS: :
      Both groups improved with treatment. Hypnotherapy resulted in superior PGI-I
      scores compared with behavioral therapy. Voiding and OAB-q SF results trended
      toward greater improvement with hypnotherapy. As a pilot study, recruitment was
      underpowered to find statistical differences between groups' voids and OAB
      scores. These findings support the need for an expanded trial that could likely
      show hypnotherapy to be superior in OAB treatment.

PMID- 22453229
TI  - Resident opinions on vaginal hysterectomy training.
AB  - OBJECTIVES: : The purpose of this study was to explore resident opinions about
      vaginal hysterectomy training and to evaluate future practice patterns and
      impediments to continuing vaginal hysterectomies after graduation. METHODS: : An
      anonymous survey was e-mailed to fourth-year gynecology residents before
      graduation. The survey assessed opinions on vaginal hysterectomy training and
      future practice plans. RESULTS: : One hundred eighty-three residents responded
      from 41 states. Most residents (75%) think vaginal hysterectomy training has been
      adequate to prepare them for future practice. Residents were more likely to
      respond that their training was adequate if they had performed more than 20
      vaginal hysterectomies and if they had learned morcellation techniques. Only 42%
      of residents report vaginal route as their preferred route for hysterectomy.
      CONCLUSIONS: : Most residents feel that training in vaginal hysterectomy has been
      adequate to prepare them for their future practice, although they are more likely
      to feel prepared if they have performed more than 20 vaginal hysterectomies.

PMID- 22453230
TI  - Percutaneously assisted cystoscopic removal of intravesical mesh erosion.
AB  - This describes a novel approach to cystoscopic removal of a mesh erosion
      occurring 3 months after anterior vaginal repair with mesh augmentation.

PMID- 22453231
TI  - Photochemical oxazole-nitrile conversion downstream of rhizoxin biosynthesis and
      its impact on antimitotic activity.
AB  - Through metabolic profiling of mutants and wild type of the endofungal bacterium
      Burkholderia rhizoxinica two novel rhizoxin derivatives with unusual nitrile
      substitutions were discovered. The nitrile groups result from a photochemical
      oxidative cleavage of the oxazolyl moiety. In vitro studies revealed that the
      photooxidation by singlet oxygen also takes place in the absence of a
      photosensitizer, and that also a thiazolyl-substituted rhizoxin analogue
      undergoes the same transformation. The resulting nitriles have antimitotic
      properties but are significantly less active than the parent compounds. These
      results highlight the impact of photoreactions onto the antiproliferative agent
      and encourage the introduction of bioisosteric groups that render the compound
      less susceptible towards photooxidation.

PMID- 22453232
TI  - A gene variant near ATM is significantly associated with metformin treatment
      response in type 2 diabetes: a replication and meta-analysis of five cohorts.
AB  - AIMS/HYPOTHESIS: In this study we aimed to replicate the previously reported
      association between the glycaemic response to metformin and the SNP rs11212617 at
      a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple
      additional populations. METHODS: Incident users of metformin selected from the
      Diabetes Care System West-Friesland (DCS, n = 929) and the Rotterdam Study (n =
      182) from the Netherlands, and the CARDS Trial (n = 254) from the UK were
      genotyped for rs11212617 and tested for an association with both HbA(1c)
      reduction and treatment success, defined as the ability to reach the treatment
      target of an HbA(1c) <= 7 % (53 mmol/mol). Finally, a meta-analysis including
      data from literature was performed. RESULTS: In the DCS cohort, we observed an
      association between rs11212617 genotype and treatment success on metformin (OR
      1.27, 95% CI 1.03, 1.58, p = 0.028); in the smaller Rotterdam Study cohort, a
      numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87,
      2.39, p = 0.15); while in the CARDS cohort there was no significant association.
      In meta-analyses of these three cohorts separately or combined with the
      previously published cohorts, rs11212617 genotype is associated with metformin
      treatment success (OR 1.24, 95% CI 1.04, 1.49, p = 0.016 and OR 1.25, 95% CI
      1.33, 1.38, p = 7.8 * 10(-6), respectively). CONCLUSIONS/INTERPRETATION: A gene
      variant near ATM is significantly associated with metformin treatment response in
      type 2 diabetic patients from the Netherlands and the UK. This is the first
      robustly replicated common susceptibility locus found to be associated with
      metformin treatment response.

PMID- 22453233
TI  - Increased CD133 expression after preoperative chemoradiotherapy in rectal cancers
      other than mucin-rich tumors.
AB  - This study is to characterize the sequential change in CD133 expression after
      preoperative chemoradiotherapy (CRT) in rectal cancer and its impact on
      postoperative prognosis. Forty-one patients with rectal cancer who had received
      CRT before surgery were selected retrospectively. In each case,
      immunohistochemical analysis was performed to compare CD133 expression in biopsy
      specimens taken before and after CRT. After CRT, CD133 expression was
      significantly increased in 14 (34%) patients, mildly increased in 25 (61%), and
      decreased in 2 (5%). However, no mucin-rich tumors showed high CD133 expression
      before or after CRT (p < 0.001). Disease-free survival and overall survival were
      significantly poorer in patients with significantly increased CD133 (p = 0.049
      and p = 0.038, respectively). Increased CD133 after CRT is a significant
      prognostic factor in rectal cancer patients treated with preoperative CRT and
      surgical resection. CD133 might be an essential cancer stem cell marker.

PMID- 22453234
TI  - Hybrid microtubes of polyoxometalate and fluorescence dye with tunable
      photoluminescence.
AB  - Fluorescent microtubes based on alpha-Keggin tungstosilicate and fluorescein
      (SiW(12)-F) have been obtained by using a simple method, which present tunable
      photoluminescence from sky blue to green to red by variation of excitation light.
      The SiW(12) component can inhibit photobleaching of fluorescein.

PMID- 22453235
TI  - Detection of allosteric kinase inhibitors by displacement of active site probes.
AB  - Non-adenosine triphosphate (ATP) competitive, allosteric inhibitors provide a
      promising avenue to develop highly selective small-molecule kinase inhibitors.
      Although this class of compounds is growing, detection of such inhibitors can be
      challenging as standard kinase activity assays preferentially detect compounds
      that bind to active kinases in an ATP competitive manner. We have previously
      described a time-resolved fluorescence resonance energy transfer (TR-FRET)-based
      kinase binding assay using the competitive displacement of ATP competitive active
      site fluorescent probes ("tracers"). Although this format has gained acceptance,
      published data with this and related formats are almost entirely without examples
      of non-ATP competitive compounds. Thus, this study addresses whether this format
      is useful for non-ATP competitive inhibitors. To this end, 15 commercially
      available non-ATP competitive inhibitors were tested for their ability to
      displace ATP competitive probes. Despite the diversity of both compound
      structures and their respective targets, 14 of the 15 compounds displaced the
      tracers with IC(50) values comparable to literature values. We conclude that such
      binding assays are well suited for the study of non-ATP competitive inhibitors.
      In addition, we demonstrate that allosteric inhibitors of BCR-Abl and MEK bind
      preferentially to the nonphosphorylated (i.e., inactive) form of the kinase,
      indicating that binding assays may be a preferred format in some cases.

PMID- 22453237
TI  - Insights into CRAC channel gating and ion permeation.

PMID- 22453236
TI  - Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue
      development during mouse embryogenesis.
AB  - Mutations of the CUL4B ubiquitin ligase gene are causally linked to syndromic X
      linked mental retardation (XLMR). However, the pathogenic role of CUL4B mutations
      in neuronal and developmental defects is not understood. We have generated mice
      with targeted disruption of Cul4b, and observed embryonic lethality with
      pronounced growth inhibition and increased apoptosis in extra-embryonic tissues.
      Cul4b, but not its paralog Cul4a, is expressed at high levels in extra-embryonic
      tissues post implantation. Silencing of CUL4B expression in an extra-embryonic
      cell line resulted in the robust accumulation of the CUL4 substrate p21(Cip1/WAF)
      and G2/M cell cycle arrest, which could be partially rescued by silencing of
      p21(Cip1/WAF). Epiblast-specific deletion of Cul4b prevented embryonic lethality
      and gave rise to viable Cul4b null mice. Therefore, while dispensable in the
      embryo proper, Cul4b performs an essential developmental role in the extra
      embryonic tissues. Our study offers a strategy to generate viable Cul4b-deficient
      mice to model the potential neuronal and behavioral deficiencies of human CUL4B
      XLMR patients.

PMID- 22453238
TI  - Insights into Chinese prostate cancer with RNA-seq.

PMID- 22453239
TI  - Mapping enhancer and promoter interactions.

PMID- 22453240
TI  - The mechanisms of IDH mutations in tumorigenesis.

PMID- 22453241
TI  - Phospholipid scramblase 1 regulates Toll-like receptor 9-mediated type I
      interferon production in plasmacytoid dendritic cells.
AB  - Toll-like receptor 9 (TLR9) senses microbial DNA in the endosomes of plasmacytoid
      dendritic cells (pDCs) and triggers MyD88-dependent type I interferon (IFN)
      responses. To better understand TLR9 biology in pDCs, we established a yeast two
      hybrid library for the identification of TLR9-interacting proteins. Here, we
      report that an IFN-inducible protein, phospholipid scramblase 1 (PLSCR1),
      interacts with TLR9 in pDCs. Knockdown of PLSCR1 expression by siRNA in human pDC
      cell line led to a 60-70% reduction of IFN-alpha responses following CpG-ODN
      (oligodeoxynucleotide) stimulation. Primary pDCs from PLSCR1-deficient mice
      produced lower amount of type 1 IFN than pDCs from the wild-type mice in response
      to CpG-ODN, herpes simplex virus and influenza A virus. Following CpG-A
      stimulation, there were much lower amounts of TLR9 in the early endosomes
      together with CpG-A in pDCs from PLSCR1-deficient mice. Our study demonstrates
      that PLSCR1 is a TLR9-interacting protein that plays an important role in pDC's
      type 1 IFN responses by regulating TLR9 trafficking to the endosomal compartment.

PMID- 22453242
TI  - Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting
      subcomplex stability and formation through direct interactions.
AB  - The WAVE regulatory complex (WRC), consisting of WAVE, Sra, Nap, Abi, and
      HSPC300, activates the Arp2/3 complex to control branched actin polymerization in
      response to Rac activation. How the WRC is assembled in vivo is not clear. Here
      we show that Nudel, a protein critical for lamellipodia formation, dramatically
      stabilized the Sra1-Nap1-Abi1 complex against degradation in cells through a
      dynamic binding to Sra1, whereas its physical interaction with HSPC300 protected
      free HSPC300 from the proteasome-mediated degradation and stimulated the HSPC300
      WAVE2 complex formation. By contrast, Nudel showed little or no interactions with
      the Sra1-Nap1-Abi1-WAVE2 and the Sra1-Nap1-Abi1-HSPC300 complexes as well as the
      mature WRC. Depletion of Nudel by RNAi led to general subunit degradation and
      markedly attenuated the levels of mature WRC. It also abolished the WRC-dependent
      actin polymerization in vitro and the Rac1-induced lamellipodial actin network
      formation during cell spreading. Therefore, Nudel is important for the early
      steps of the WRC assembly in vivo by antagonizing the instability of certain WRC
      subunits and subcomplexes.

PMID- 22453243
TI  - Natural history of merkel cell carcinoma following locoregional recurrence.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine
      malignancy with an ill-defined natural history following locoregional recurrence.
      METHODS: This is a retrospective review of patients with MCC diagnosed at the
      Mayo Clinic from 1981 to 2008. For each outcome (subsequent locoregional
      recurrence, distant recurrence, and death) the survival-free of the outcome was
      estimated using the Kaplan-Meier method. Associations of patient and clinical
      characteristics with the outcomes were assessed by fitting Cox proportional
      hazards regression models. RESULTS: Among the 240 patients diagnosed with MCC, 70
      (29%) patients were identified who developed locoregional recurrence as the first
      site of recurrence. The median time from diagnosis to locoregional recurrence was
      6 months. The pattern of first locoregional failure in this group includes 25
      (10.4%) local, 18 (7.5%) in-transit, and 27 (11.3%) nodal recurrences.
      Recurrences were most commonly treated by surgery and radiation. At 3 years after
      the initial recurrence, locoregional recurrence-free survival was 75% and the
      distant recurrence-free survival was 56%. Locoregional recurrence is a poor
      prognostic sign associated with a 3-year overall survival of 39%. Nodal status at
      time of original surgery and time to first recurrence were important predictors
      of distant recurrence (P < 0.006) and overall survival following locoregional
      recurrence (P < 0.001). CONCLUSIONS: Locoregional recurrence is a substantial
      problem in patients with MCC and is a poor prognostic sign. In those patients who
      experience a locoregional recurrence, aggressive efforts to regain locoregional
      control appear warranted and may result in long-term survival.

PMID- 22453245
TI  - Cadence patterns and peak cadence in US children and adolescents: NHANES, 2005
      2006.
AB  - Cadence (steps per minute) is one of the temporal-spatial parameters of walking
      gait, is related to intensity, and can be used to identify patterns of ambulatory
      behavior in free living by tracking time spent at incrementally higher cadences.
      In addition, peak cadence, a simple indicator of best natural ambulatory effort,
      can be captured. Such indicators have been used to study adult ambulatory
      behavior in a representative sample, but similar analyses for children and
      adolescents are limited to a single small and select sample. PURPOSE: The study's
      purpose was to describe in children and adolescents 1) free-living cadence
      patterns (i.e., time spent at incrementally higher cadence bands) and 2) peak
      cadence indicators (i.e., peak 60 min, peak 30 min, and peak 1 min) by sex, age,
      and body mass index. METHODS: Cadence patterns and peak cadence were derived from
      2005-2006 National Health and Nutrition Examination Survey accelerometer data
      representing 2610 children and adolescents (1281 boys and 1329 girls, age 6-19
      yr). Data were described by sex, age group (6-11, 12-15, and 16-19 yr), and body
      mass index-defined weight status (normal, overweight, obese). RESULTS: On
      average, US children and adolescents spent =/~4 h . d(-1) at zero cadence during
      wearing time, =/~8.9 h . d(-1) between 1 and 59 steps per minute, =/~22 min . d(
      1) at cadences of 60-79 steps per minute, =/~13 min at 80-99 steps per minute,
      =/~9 min at 100-119 steps per minute, and =/~3 min at cadences >= 120 steps per
      minute. Peak 60-min, 30-min, and 1-min cadences were 72, 85, and 118 steps per
      minute, respectively. CONCLUSIONS: US children and adolescents seem to spend
      relatively few minutes in daily life engaged in activities that elicit step
      accumulation patterns indicative of normal walking speeds, let alone those
      associated with higher intensity activities.

PMID- 22453246
TI  - Coingesting glucose and fructose in the cold potentiates exogenous CHO oxidation.
AB  - PURPOSE: Current understanding of exogenous CHO metabolism during cold exposure
      is limited but suggests that exogenous glucose oxidation reaches a maximum of
      ~200 mg . min(-1) at a glucose ingestion rate of 400 mg . min(-1). The aim of the
      present study was to determine whether ingesting glucose in combination with
      fructose (GLU + FRU) after 60 min of cold exposure could increase the rate of
      exogenous CHO oxidation and reduce the reliance on endogenous CHO reserves
      compared with ingesting a glucose drink (GLU). METHODS: Six healthy non-cold
      acclimatized men were exposed to low-intensity shivering (~2.5 times resting
      metabolic rate) for a duration of 150 min on two occasions. Subjects consumed a
      (13)C-enriched CHO drink ((13)C-enriched glucose and fructose) providing 400 mg .
      min(-1) of glucose + 400 mg . min(-1) of fructose (GLU + FRU) or 800 mg . min(-1)
      of glucose alone (GLU) after 60 min of cold exposure. RESULTS: The peak exogenous
      CHO oxidation rate was 30% greater in GLU + FRU compared with GLU (209 +/- 62 vs
      159 +/- 42 mg . min(-1), respectively, P < 0.05). This contributed to a 16%
      increase in total CHO oxidation (406 +/- 100 vs 351 +/- 80 mg . min(-1),
      respectively, P < 0.05). The utilization of endogenous CHO sources was the same
      between experimental conditions but was nearly 2.5 times lower than values
      previously reported by our laboratory when only water was ingested (192-197 vs
      456 mg . min(-1), respectively). CONCLUSIONS: This study demonstrates that the
      greater exogenous and total CHO oxidation rate observed in the GLU + FRU
      condition was a result of increased systemic appearance of CHO from consuming
      multiple transportable CHO and/or the supplementary substrate provided from
      fructose conversion to glucose and lactate in the liver.

PMID- 22453247
TI  - Development of a neuromuscular electrical stimulation protocol for sprint
      training.
AB  - PURPOSE: Sprint training is associated with several beneficial adaptations in
      skeletal muscle, including an enhancement of sarcoplasmic reticulum (SR) Ca(2+)
      release. Unfortunately, several patient populations (e.g., the elderly, those
      with cardiac dysfunction) that might derive great benefit from sprint exercise
      are unlikely to tolerate it. The purpose of this report was to describe the
      development of a tolerable neuromuscular electrical stimulation (NMES) protocol
      that induces skeletal muscle adaptations similar to those observed with sprint
      training. METHODS: Our NMES protocol was modeled after a published sprint
      exercise protocol and used a novel electrode configuration and stimulation
      sequence to provide adequate training stimulus while maintaining subject
      tolerance. Nine young, healthy subjects (four men) began and completed the
      training protocol of the knee extensor muscles. RESULTS: All subjects completed
      the protocol, with ratings of discomfort far less than those reported in studies
      of traditional NMES. Training induced significant increases in SR Ca(2+) release
      and citrate synthase activity (~16% and 32%, respectively), but SR Ca(2+) uptake
      did not change. The percentage of myosin heavy chain IIx isoform was decreased
      significantly after training. At the whole muscle level, neither central
      activation nor maximum voluntary isometric contraction force were significantly
      altered, although isometric force did exhibit a trend toward an increase (~3%, P
      = 0.055). Surprisingly, the NMES training produced a significant increase in
      muscle cross-sectional area (~3%, P = 0.04). CONCLUSIONS: It seems that an
      appropriately designed NMES protocol can mimic many of the benefits of sprint
      exercise training, with a low overall time commitment and training volume. These
      findings suggest that NMES has the potential to bring the benefits of sprint
      exercise to individuals who are unable to tolerate traditional sprint training.

PMID- 22453249
TI  - Neural modulation of muscle-tendon control strategy after a single practice
      session.
AB  - PURPOSE: The purpose of the present study was to examine a hypothesis that the
      musculotendinous behavior during a propelling action with a countermovement can
      be altered by a single practice session through modulation of neuromuscular
      activities. METHODS: Eight males performed unilateral maximal plantarflexion with
      (CMJ) and without (noCMJ) countermovement before and after a practice consisting
      of six sets of three repetitions of unilateral CMJ exercises. Measurements
      included EMG activities of the triceps surae and tibialis anterior muscles and
      the fascicle behavior of the gastrocnemius by ultrasonography, and impulse was
      calculated from the force-time data. The change in tendon length was also
      estimated. RESULTS: The impulse in CMJ increased after the practice, but that in
      noCMJ did not. After the practice, the magnitude of fascicle lengthening and
      shortening in CMJ decreased, which was accompanied by an increase in tendon
      shortening without change in the ankle joint range of motion. The time lag from
      the onset of reaction force to that of EMG activities of the triceps surae
      muscles was shortened after the practice. CONCLUSIONS: The results support the
      hypothesis and indicate that, as a neural modulation through a single practice,
      the muscle-tendon unit behavior during CMJ can be optimized to improve the
      performance.

PMID- 22453248
TI  - Performance benefits of rehydration with intravenous fluid and oral glycerol.
AB  - PURPOSE: Intravenous (IV) saline has been used by athletes attempting to
      accelerate rehydration procedures. The diuresis from IV rehydration may be
      circumvented through the concomitant use of oral glycerol. We aimed to examine
      the effects of rehydrating with four different regimens of IV fluid and oral
      glycerol on subsequent 40-km cycling time trial performance. METHODS: Nine
      endurance-trained men were dehydrated by 4% bodyweight via exercise in the heat.
      They then rehydrated with 150% of the fluid lost via four protocols using a
      randomized crossover design: 1) oral = sports drink and water; 2) oral glycerol =
      sports drink, water, and glycerol; 3) IV = half as normal saline, half of sports
      drink, and water; and 4) IV with oral glycerol = half as normal saline, half as
      sports drink, water, and glycerol. After this, they completed a 40-km cycling
      performance test in the heat. RESULTS: Compared with oral rehydration, there were
      significant performance benefits (P < 0.05) when rehydrating with oral glycerol
      (improved time to complete 40 km by 3.7%), IV (3.5%), and IV with oral glycerol
      (4.1%). Plasma volume restoration was highest in IV with oral glycerol, then IV,
      then oral glycerol, then oral (P < 0.01 for all of these comparisons). There were
      no differences in HR, tympanic/skin temperatures, sweat rate, blood lactate
      concentration, thermal stress, or RPE between groups. CONCLUSIONS: Combining IV
      fluid with oral glycerol resulted in the greatest fluid retention; however, it
      did not improve exercise performance compared with either modality alone.

PMID- 22453250
TI  - Nutrition and exercise reduce excessive weight gain in normal-weight pregnant
      women.
AB  - PURPOSE: This study aimed to evaluate the effect of an exercise program of two
      different intensities, with nutritional control, on gestational weight gain
      (GWG), infant birth weight, and maternal weight retention at 2 months postpartum
      (2 mopp). METHODS: Pregnant women (prepregnancy body mass index = 18.5-24.9 kg.m)
      were randomized at study entry (16-20 wk of gestation) to a low-intensity (LI,
      30% HR reserve (HRR), n = 23) or moderate-intensity (MI, 70% HRR, n = 26)
      exercise program, with nutritional control. The exercise program consisted of
      walking sessions three to four times per week, gradually increasing exercise time
      from 25 to 40 min per session. Forty-five normal-weight women who did not
      participate in any structured exercise program during pregnancy and had singleton
      births were used as a historical control group. RESULTS: Total GWG was higher in
      the control group (18.3 +/- 5.3 kg) compared with the LI (15.3 +/- 2.9 kg, P =
      0.01) and MI (14.9 +/- 3.8 kg, P = 0.003) groups. During the intervention, GWG
      was similar in both intervention groups, with weekly rates of weight gain of 0.49
      +/- 0.1 and 0.47 +/- 0.1 kg.wk in the LI and MI groups, respectively. Excessive
      GWG during the intervention was prevented in 70% of the women in the LI group and
      77% of those in the MI group. Excessive GWG occurred before the intervention
      began. At 2 mopp, 18% and 28% of the women in the LI and MI groups, respectively,
      retained <=2.0 kg compared with only 7% of those in the control group. Infant
      birth weight was not different between the groups. CONCLUSIONS: Results suggest
      that a prenatal nutrition and exercise program regardless of exercise intensity,
      reduced excessive GWG and decreased weight retention at 2 mopp in women of normal
      weight before pregnancy.

PMID- 22453253
TI  - Synthesis and properties of beta,beta-sp3-hybridized subphthalocyanine analogues.
AB  - A beta,beta-sp(3)-hybridized subphthalocyanine analogue, dibenzosubtriazachlorin,
      was synthesized, and its significantly split Q band absorptions in longer and
      shorter wavelength regions relative to those of subphthalocyanines were revealed.
      The effect of benzo-annulation to a subtriazachlorin structure on the position of
      the split Q bands as well as the electronic structures was also investigated.

PMID- 22453252
TI  - Melphalan 180 mg/m2 can be safely administered as conditioning regimen before an
      autologous stem cell transplantation (ASCT) in multiple myeloma patients with
      creatinine clearance 60 mL/min/1.73 m2 or lower with use of palifermin for
      cytoprotection: results of a phase I trial.
AB  - High-dose melphalan 140 mg/m2 is the standard of care for patients with multiple
      myeloma (MM) with renal insufficiency (RI). Palifermin as a cytoprotective agent
      has demonstrated efficacy in reducing the intensity and duration of oral
      mucositis (OM) in patients who receive intensive chemotherapy/radiotherapy. There
      is no prospective data on the use of palifermin in patients with MM with RI.
      ELIGIBILITY CRITERIA: creatinine clearance <=60 mL/minute/1.73 m2, age >18 years,
      no dialysis, no active OM, and a suitable candidate for autologous stem cell
      transplant (ASCT). Melphalan dose ranged from 140 to 200 mg/m2 and escalated at
      the increment of 20 mg/m2. Six dosages of palifermin 60 mcg/kg/day were given
      intravenously between day -5 to day +3. Dose escalations were to stop if dose
      limiting toxicities (DLTs) occurred at melphalan dose in >=2 of 3 patients, with
      that dose declared as the maximal administered dose and the level below where <=1
      of 6 patients had DLTs was considered the maximally tolerated dose (MTD).
      Nineteen patients were enrolled from June 2007 to June 2011. Data on 15 evaluable
      patients is reported as 4 patients were removed. Median age was 59 years (range,
      36-67 years). The overall incidence of OM >= grade 3 was 53% (8 of 15) and a
      median duration of >=grade 3 OM was 6.5 days (range, 3-42 days). One patient in
      L2 (melphalan 160 mg/m2) developed atrial fibrillation on day +9. Two patients in
      L4 (melphalan 200 mg/m2) developed grade 4 OM, hence reaching DLT. No DLT was
      observed in 6 patients enrolled in L3 (melphalan 180 mg/m2). Palifermin has
      permitted safe dose escalation of melphalan up to 180 mg/m(2) in patients with
      RI.

PMID- 22453254
TI  - Determining the contribution of the energy systems during exercise.
AB  - One of the most important aspects of the metabolic demand is the relative
      contribution of the energy systems to the total energy required for a given
      physical activity. Although some sports are relatively easy to be reproduced in a
      laboratory (e.g., running and cycling), a number of sports are much more
      difficult to be reproduced and studied in controlled situations. This method
      presents how to assess the differential contribution of the energy systems in
      sports that are difficult to mimic in controlled laboratory conditions. The
      concepts shown here can be adapted to virtually any sport.    The following
      physiologic variables will be needed: rest oxygen consumption, exercise oxygen
      consumption, post-exercise oxygen consumption, rest plasma lactate concentration
      and post-exercise plasma peak lactate. To calculate the contribution of the
      aerobic metabolism, you will need the oxygen consumption at rest and during the
      exercise. By using the trapezoidal method, calculate the area under the curve of
      oxygen consumption during exercise, subtracting the area corresponding to the
      rest oxygen consumption. To calculate the contribution of the alactic anaerobic
      metabolism, the post-exercise oxygen consumption curve has to be adjusted to a
      mono or a bi-exponential model (chosen by the one that best fits). Then, use the
      terms of the fitted equation to calculate anaerobic alactic metabolism, as
      follows: ATP-CP metabolism = A(1;) (mL . s(-1)) x t(1;) (s). Finally, to
      calculate the contribution of the lactic anaerobic system, multiply peak plasma
      lactate by 3 and by the athlete's body mass (the result in mL is then converted
      to L and into kJ).    The method can be used for both continuous and intermittent
      exercise. This is a very interesting approach as it can be adapted to exercises
      and sports that are difficult to be mimicked in controlled environments. Also,
      this is the only available method capable of distinguishing the contribution of
      three different energy systems. Thus, the method allows the study of sports with
      great similarity to real situations, providing desirable ecological validity to
      the study.

PMID- 22453255
TI  - Molecular tuning in highly fluorescent dithieno[3,2-b:2',3'-d]pyrrole-based
      oligomers: effects of N-functionalization and terminal aryl unit.
AB  - A series of eight conjugated oligomers consisting of central dithieno[3,2-b:2',3'
      d]pyrroles (DTPs) end-capped with either thienyl or phenyl groups have been
      prepared from N-alkyl-, N-aryl-, and N-acyl-dithieno[3,2-b:2',3'-d]pyrroles via
      Stille and Suzuki cross-coupling. The DTP-based quaterthiophene, N-phenyl-2,6
      bis(2-thienyl)dithieno-[3,2-b:2',3'-d]pyrrole was characterized via X-ray
      crystallography and was found to crystallize in the orthorhombic space group
      Pna2(1) with a = 10.8666(3) A, b = 22.8858(6) A, c = 7.4246(2) A, and Z = 4. The
      full oligomeric series was thoroughly investigated via photophysical,
      electrochemical, and DFT calculations in order to correlate the cumulative
      effects of both aryl end-groups and N-functionalization on the resulting optical
      and electronic properties. Through such molecular tuning, it was found to be
      possible to modulate the HOMO energy by as much as 0.32 V and to generate highly
      fluorescent oligomers with solution fluorescence efficiencies as high as 92%.

PMID- 22453256
TI  - Keeping the balance as we move forward.

PMID- 22453257
TI  - Vaginal placement of synthetic mesh for pelvic organ prolapse.
AB  - Since 2004, use of synthetic mesh has increased in vaginal surgery for the
      treatment of pelvic organ prolapse. However, concerns exist about the safety and
      efficacy of transvaginally placed mesh. Based on the currently available limited
      data, although many patients undergoing mesh-augmented vaginal repairs heal well
      without problems, there seems to be a small but significant group of patients who
      experience permanent and life-altering sequelae, including pain and dyspareunia,
      from the use of vaginal mesh. The American College of Obstetricians and
      Gynecologists and the American Urogynecologic Society provide background
      information on the use of vaginally placed mesh for the treatment of pelvic organ
      prolapse and offer recommendations for practice.

PMID- 22453258
TI  - Surgical treatment of vaginal vault prolapse:  a historic summary and review of
      outcomes.
AB  - OBJECTIVES: This study aimed to review the history of surgical treatment of
      vaginal vault prolapse, its current treatments, and its outcomes. METHODS: A
      PubMed search was conducted using the following terms: vaginal vault prolapse,
      apical prolapse, surgical treatments, culdoplasty, uterosacral ligament fixation,
      and sacral colpopexy. RESULTS: Vaginal vault prolapse is a common condition with
      many surgical treatment options. Surgical principles and treatment of this
      condition dates back to the 19th century. Native tissue repairs such as McCall
      culdoplasty, uterosacral ligament fixation, and sacrospinous fixation have high
      overall success rates with restoring apical anatomy. Sacral colpopexy also has
      excellent success rates when mesh is needed to augment repairs. CONCLUSIONS:
      There are many options for the treatment of vaginal vault prolapse. Modifications
      have been made to the original procedures; however, the basic principles are
      still applicable and include attaching the vaginal apex to level 1 support.

PMID- 22453259
TI  - Assessment of women with defecatory dysfunction and manual splinting using
      dynamic pelvic floor magnetic resonance imaging.
AB  - OBJECTIVE: This study aimed to describe magnetic resonance imaging (MRI) findings
      in women with defecatory dysfunction who perform manual splinting. METHODS: This
      is a retrospective study of 29 patients from a single urogynecology center who
      presented with complaints of defecatory dysfunction and who reported manual
      splinting to assist with bowel movements. Patients were scheduled for an MRI
      study with a novel "splinting" protocol to evaluate the effects of their manual
      splinting on the pelvic floor. The protocol involved asking patients to splint
      during the MRI, as they normally would when trying to defecate. The goal was to
      evaluate any change in pelvic anatomy and compensation for an anatomic defect
      that could potentially lead to their defecatory dysfunction. Magnetic resonance
      images of the pelvis were obtained at rest, with pelvic floor contraction, with
      Valsalva, and during manual splinting. These images were then reviewed by
      radiologists who evaluated various parameters, including anorectal angle, levator
      ani muscle integrity, and the presence of rectocele, cystocele, apical prolapse,
      and enterocele. The external and internal anal sphincters were also evaluated for
      continuity. RESULTS: From September 2008 to October 2010, 29 women reported
      defecatory dysfunction and the need for manual splinting. Their mean (SD) age was
      55.2 (10.5) years. Magnetic resonance images showed a rectocele in 86.2% of the
      study group, cystocele in 75.9%, enterocele in 10.3%, and a defect of the levator
      ani muscles in 17.2%. Twenty-one (72.4%) women had more than 1 of these defects.
      In addition, 27.6% had an anorectal angle less than 90 degrees or greater than
      105 degrees.Patients in the study group splinted in the vagina (58.6%), on the
      perineum (31.0%), or on the buttock (10.3%). In all but 1 woman (96.6%),
      splinting improved or completely corrected the identified defect(s) as evidenced
      with MRI. Among those who used vaginal splinting, 52.9% of defects were corrected
      and 47.1% were improved. Perineal splinting corrected 55.6% and improved 33.3% of
      cases and was ineffective in 11.1% of cases, whereas buttock splinting corrected
      33.3% and improved 66.7% of cases. CONCLUSIONS: Most women in our study group who
      used manual splinting to assist in defecation are compensating for a pelvic floor
      defect that can be detected on MRI. Magnetic resonance imaging of the pelvis may
      help elucidate the etiology of the defecatory dysfunction in some women and may
      assist pelvic reconstructive surgeons in planning surgical correction of pelvic
      floor defects. Magnetic resonance imaging may also identify defects in the pelvic
      floor that are, at the present time, not amenable to surgical correction.

PMID- 22453260
TI  - Bladder perforation during tension-free vaginal tape procedures:  abdominal
      versus vaginal approach.
AB  - OBJECTIVE: Bladder perforation rates for the tension-free vaginal tape (TVT) are
      higher with inexperienced surgeons. The purpose of this study was to examine if
      surgical approach affects this rate. METHODS: We performed a retrospective cohort
      study of consecutive patients undergoing a TVT as the sole procedure. All cases
      were performed by senior residents using 2 different surgical approaches-vaginal
      or abdominal trocar passage. Power analysis indicated that 103 patients in each
      group (vaginal and abdominal approach) were required to demonstrate a 50%
      reduction in perforation rates. RESULTS: The rate of perforation was 37.9% (95%
      confidence interval [CI], 28.5%-47.3%) for the vaginal compared with 6.8% (95%
      CI, 1.9%-11.7%) for the abdominal technique (P < 0.001). The relative risk that
      the abdominal technique results in bladder injury compared with the original
      transvaginal was 0.18 (95% CI, 0.08-0.38). CONCLUSIONS: Bladder perforation
      occurs significantly less frequently with abdominal needle placement for the TVT
      procedure. We recommend this technique to less experienced surgeons.

PMID- 22453264
TI  - Postoperative voiding dysfunction following posterior colporrhaphy.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the rate of
      postoperative urinary retention in patients undergoing posterior colporrhaphy.
      This is compared with the rate of postoperative urinary retention in patients
      undergoing suburethral sling placement. METHODS: A retrospective analysis of
      women treated surgically for either a symptomatic posterior compartment defect or
      stress urinary incontinence was performed. The preoperative, operative, and
      postoperative records of women who underwent a sole procedure of a posterior
      colporrhaphy or tension-free suburethral sling by 2 fellowship-trained
      urogynecologists were reviewed and compared. RESULTS: Significantly more
      posterior colporrhaphy patients failed their voiding trial (32.4% +/- 12%) than
      suburethral sling patients (15% +/- 17%; P = 0.030). After replacement of a Foley
      catheter, the total length of catheterization was longer in the posterior
      colporrhaphy group (3.2 +/- 0.9 days) than that in the suburethral sling group
      (1.8 +/- 0.4 days; P = 0.007). No patients in either group demonstrated long-term
      voiding dysfunction, and no patients required further surgical management to
      reverse their transient voiding dysfunction. CONCLUSIONS: In this study, the rate
      of postoperative transient urinary retention following posterior colporrhaphy is
      32.4%, which is significantly higher than the rate observed following suburethral
      sling placement. Although the reason for this higher rate is unclear, it may be
      related to postoperative pain. Although it is standard practice to assess voiding
      function after suburethral sling placement, the findings of our study suggest
      that physicians should also consider assessing postoperative voiding function
      following posterior colporrhaphy.

PMID- 22453265
TI  - Pelvic organ prolapse quantification use in the literature.
AB  - OBJECTIVE: This study aimed to determine whether the Pelvic Organ Prolapse
      Quantification (POPQ) system should be simplified based on its use in the peer
      reviewed literature. METHODS: The American Journal of Obstetrics and Gynecology,
      Obstetrics and Gynecology, and International Urogynecology Journal were used for
      this study. All articles relating to pelvic organ prolapse published in these
      journals from January 2005 to December 2010 were reviewed for their use of the
      POPQ system. The POPQ points described in the Materials and/or Results sections
      of these articles were recorded. RESULTS: Two hundred eighty-three articles using
      the POPQ system were identified. One hundred thirty-two (47%) articles used the
      POPQ system but only to determine the stage of prolapse. Specific points were not
      mentioned. One hundred two (36%) articles evaluated specific POPQ points (Aa, Ba,
      Ap, Bp, C, D). Forty-nine (17%) articles evaluated points Gh, Pb, and Tvl.
      CONCLUSIONS: The POPQ system, based on its use in the peer-reviewed literature,
      may need revisions. An abbreviated version of the system may be considered,
      allowing for more widespread use.

PMID- 22453266
TI  - Teaching of pelvic organ prolapse quantification system among
      obstetrics/gynecology and urology residents in the United States.
AB  - OBJECTIVES: The objective of this study was to compare the Pelvic Organ Prolapse
      Quantification (POPQ) system teaching practices among obstetrics/gynecology
      (ob/gyn) and urology residents in the United States. METHODS: Anonymous Web-based
      survey was e-mailed to the residency program directors/coordinators of all
      urology and ob/gyn programs in the United States with a request to forward it to
      all their residents. Fisher exact and z tests for proportions and multivariate
      regression analysis examining factors associated with POPQ system use were used
      in the statistical analysis. RESULTS: Sixty percent (45/75) of urology and 78.9%
      (105/133) of responding ob/gyn residents (P = 0.006) reported having used the
      POPQ system, whereas 42.7% and 59.4% of them, respectively, reported current use
      (P = 0.03). The latter also reported more protected educational time (P < 0.001),
      more urogynecologists in their programs (P = 0.032), and learning more frequently
      from drawings (P = 0.025). Opinions about the routine clinical and scientific
      usefulness of POPQ system and the perceived difficulty in learning it did not
      vary between groups. After performing multivariate logistic regression analysis,
      the presence of a fellowship, the number of subspecialists in the program, and
      the number of POPQ system teaching sessions were the studied variables found to
      contribute independently to the residents' use of that system. CONCLUSIONS:
      Obstetrics/gynecology residents use POPQ system more frequently than do urology
      residents. This could be related to differences in teaching practices between
      urology and ob/gyn programs.

PMID- 22453268
TI  - Mindfulness-based stress reduction for treatment of urinary urge incontinence:  a
      pilot study.
AB  - OBJECTIVE: The objective of the study was to evaluate if a mindfulness-based
      stress reduction program is a viable treatment worthy of further evaluation for
      the treatment of urinary urge incontinence. METHODS: This was a single-arm pilot
      study of 7 women who participated in an 8-week mindfulness-based stress reduction
      program to evaluate its effectiveness in reducing urinary leakage episodes.
      Improvement was measured by 3-day bladder diary, Overactive Bladder Symptom and
      Quality of Life-Short Form, Health-Related Quality of Life, and Patient Global
      Impression of Improvement. Outcome data were analyzed by means of paired t tests.
      RESULTS: Mean incontinence episodes per day decreased from 4.14 (SD, 1.96; range,
      2.67-7.67) at baseline to 1.23 (SD, 0.93; range, 0.33-2.67) after treatment (P =
      0.0005 for change). After treatment, 5 of 7 women were improved based on the
      Patient Global Impression of Improvement, and 2 were unchanged. Significant
      improvements on both Health-Related Quality of Life and Overactive Bladder
      Symptom and Quality of Life-Short Form were reported after treatment. Results
      were sustained at 1 year in 4 of 7 women. Two women sought treatment, and one was
      lost to follow-up at 12 months. CONCLUSIONS: Mindfulness-based stress reduction
      appears to be a treatment worthy of further study, as in the short term, it is as
      effective as historical studies of drug treatment and bladder training in
      reducing urge incontinence and incontinence-related quality of life.

PMID- 22453267
TI  - TVT-Secur (Hammock) versus TVT-Obturator: a randomized trial of suburethral sling
      operative procedures.
AB  - OBJECTIVES: This study aimed to compare TVT-Secur (TVT-S) and TVT-Obturator (TVT
      O) suburethral slings for treatment of stress urinary incontinence (SUI).
      METHODS: This was a single-center, nonblinded, randomized trial of women with SUI
      who were randomized to TVT-S or TVT-O from May 2007 to April 2009. The primary
      outcome, SUI on cough stress test (CST), and quality-of-life and symptom
      questionnaires (Pelvic Floor Distress Inventory [PFDI-20] and Pelvic Floor Impact
      Questionnaire [PFIQ-7]) were assessed at 12 weeks and 1 year. RESULTS: Forty
      three women were randomized to TVT-S and 44 to TVT-O. There were no differences
      in median baseline PFDI-20 and PFIQ-7. Twenty-two (52.4%) of 42 participants
      randomized to TVT-S had a positive CST result at evaluation after 12 weeks or 1
      year, whereas 4 (9.1%) of the 44 in the TVT-O group had a positive CST result.
      The intent-to-treat analysis showed that the risk of a positive CST result was 6
      times higher after TVT-S than TVT-O (risk ratio, 6.0; 95% confidence interval
      [CI], 2.3-16.0). Among women not lost to follow-up, the risk ratio for a positive
      CST result after TVT-S compared with TVT-O was 17.9 (95% CI, 2.5-128.0) at 12
      weeks and 3.5 (95% CI, 1.1-11.0) at 1 year. Both TVT-S and TVT-O resulted in
      improved quality of life and symptoms at 12 weeks. There was no difference
      between the groups for PFDI-20 (P = 0.40) or PFIQ-7 (P = 0.43). A similar pattern
      was seen at 1 year (P = 0.85 and P = 0.36). CONCLUSIONS: The TVT-S seems to have
      a higher risk of positive postoperative CST result; however, the procedures
      result in similar improvements in quality of life and symptoms.

PMID- 22453269
TI  - Assessment of internet-based information regarding pelvic organ prolapse and
      urinary incontinence.
AB  - OBJECTIVE: This study aimed to establish descriptive data on the content,
      accuracy, and relevance of Internet-based information regarding pelvic organ
      prolapse and urinary incontinence. METHODS: Using the search terms, urinary
      incontinence, uterine prolapse, dropped uterus, cystocele, and dropped bladder,
      the first 20 Web sites that appeared in each of 3 highly used search engines were
      identified. Two experienced reviewers independently evaluated each site for
      specific content, relevance, and accuracy. RESULTS: A total of 220 individual
      sites were identified: government-, university-, and/or society-sponsored sites
      represented 14.1% of the identified sites. Private parties, community groups, or
      unknown sponsors represented 73.2% of the sites. Industry represented 12.7% of
      the sites. The year the site was created was displayed in 45.9% of the sites,
      although 66.4% of the sites contained a year of update. Overall, 45% of the sites
      were rated as mostly/completely relevant to the search term and 44% of the sites
      were rated as mostly/completely accurate. Government-, university-, and/or
      society-sponsored sites were significantly more likely to be rated
      mostly/completely relevant and mostly/completely accurate compared with all other
      site sponsors with P = 0.05 and P = 0.0003, respectively. CONCLUSIONS:
      Government, university, and/or medical societies sponsor a minority of Web sites
      compared with other sponsors but provide more comprehensive content that is more
      relevant and accurate to the topics of pelvic organ prolapse and urinary
      incontinence.

PMID- 22453270
TI  - Prolapse symptoms in overweight and obese women before and after weight loss.
AB  - OBJECTIVE: The objective of this study was to estimate the association between
      body mass index (BMI) and pelvic organ prolapse symptoms and bother among
      overweight and obese women with urinary incontinence before and after weight
      loss. METHODS: Women (N = 338) were randomized to either an intensive 6-month
      weight loss or educational program (control); they were evaluated for prolapse
      symptoms at baseline and 6 months. Symptomatic prolapse was defined as a positive
      response to at least 1 prolapse subscale question of the Urogenital Distress
      Inventory. "Bother" was defined as responses of slight, moderate, or great. Women
      with prolapse symptoms were analyzed by baseline BMI category: overweight, obese,
      and severely obese at baseline and at 6 months. Proportional odds regression and
      chi tests for trend were used for analysis. RESULTS: Age mean was 53 (SD, 10)
      years, BMI mean was 36 (SD, 6) kg/m, and 78% were white. A higher proportion of
      obese women reported feeling vaginal bulging compared with overweight women (13%
      vs 0%, P = <0.01). At baseline, 37% (n = 124) reported bothersome "lower
      abdominal pressure"; 18% (n = 62), bothersome "heaviness in the pelvic area"; and
      14% (n = 48), bothersome "pelvic discomfort when standing." Nine percent (n = 31)
      reported bothersome "feeling," and 2% (n = 6) reported bothersome "seeing a
      bulge" in the vagina. At 6 months, there were no significant differences in
      improvement of self-reported bothersome prolapse symptoms in women in the weight
      loss or the control group. CONCLUSIONS: In this study of overweight and obese
      women, increasing BMI was associated with only "feeling" a vaginal bulge. Weight
      loss did not improve bothersome prolapse symptoms.

PMID- 22453271
TI  - Missed diagnosis of complete urethral transection after sling:  the case for
      translabial ultrasound.
AB  - Patients with complications of urethral sling placement for stress urinary
      incontinence are often treated for recurrent symptoms for years after initial
      reassuring evaluation. Translabial ultrasound is a noninvasive modality with
      minimal risks that can clearly diagnose urethral mesh complications. We present a
      47-year-old premenopausal woman referred for treatment of urethral stricture and
      diverticulum 8 years after mesh sling placement. The diagnosis was made at an
      outside institution by voiding cystourethrogram and cystoscopy. However,
      translabial ultrasound confirmed the diagnosis of complete urethral transection,
      and the patient underwent a complex urethral reconstruction. Ultrasound should be
      used to evaluate patients with a history of urethral sling and persistent lower
      urinary tract symptoms. Referral to a center with advanced pelvic reconstruction
      services may be required.

PMID- 22453272
TI  - Recurrent pelvic organ prolapse in a patient with history of bladder exstrophy.
AB  - BACKGROUND: Increased risk of pelvic organ prolapse in women with a history of
      bladder exstrophy poses difficult management owing to the absence of anterior
      support and pelvic angle. We present a case of recurrent prolapse in the setting
      of bladder exstrophy and discuss factors that may warrant consideration during
      the evaluation of such patients. CASE: A 26-year-old nulliparous woman with a
      history of bladder exstrophy and pelvic organ prolapse initially repaired with a
      porcine graft sacral hysteropexy presented with suspected recurrent apical
      prolapse. After counseling, she elected to undergo second surgery. During
      exploration, cervical elongation rather than recurrent prolapse was noted.
      Therefore, the decision was made to perform a trachelectomy. CONCLUSIONS: When
      recurrent pelvic organ prolapse is reported, especially in the setting of
      complicating factors such as a history of bladder exstrophy, other differential
      diagnoses for prolapse, such as cervical elongation, should be considered.
      Initial evaluation of such patients can be tailored to evaluate for other
      possible diagnoses, clarifying the choice of options for optimal medical or
      surgical management.

PMID- 22453273
TI  - Persistent ischiorectal fistula with supralevator origin secondary to a chronic
      tubo-ovarian abscess:  report of a case and review of the literature.
AB  - BACKGROUND: Chronic tubo-ovarian abscess is an uncommon finding in postmenopausal
      women. This abscess may rupture or fistulize to adjacent organs into the
      ischiorectal space. CASE: A gravida three, para three, postmenopausal woman with
      extensive sigmoid diverticulosis presented with perianal fistula of 2 years'
      duration. Magnetic resonance imaging showed the tract to have a supralevator
      origin adjacent to the sigmoid colon. She had no recent instrumentation other
      than preoperative colonoscopy. Intraoperatively, the fistula tract origin was
      noted to be from a right tubo-ovarian abscess. She was treated with right
      salpingo-oophorectomy and tract excision/sealing. At 4-month follow-up, the
      fistula tract was healed with no further drainage. CONCLUSIONS: Tubo-ovarian
      abscess should be considered in the differential diagnosis of supralevator
      fistula in postmenopausal women when no other source can be localized.

PMID- 22453274
TI  - Single-stranded loops as end-label polarity markers for double-stranded linear
      DNA templates in atomic force microscopy.
AB  - Visualization of DNA-protein interactions by atomic force microscopy (AFM) has
      deepened our understanding of molecular processes such as DNA transcription.
      Interpretation of systems where more than one protein acts on a single template,
      however, is complicated by protein molecules migrating along the DNA. Single
      molecule AFM imaging experiments can reveal more information if the polarity of
      the template can be determined. A nucleic acid-based approach to end-labelling is
      desirable because it does not compromise the sample preparation procedures for
      biomolecular AFM. Here, we report a method involving oligonucleotide loop-primed
      synthesis for the end labelling of double-stranded DNA to discriminate the
      polarity of linear templates at the single-molecule level. Single-stranded
      oligonucleotide primers were designed to allow loop formation while retaining 3'
      single-strand extensions to facilitate primer annealing to the template.
      Following a DNA polymerase extension, the labelled templates were shown to have
      the ability to form open promoter complexes on a model nested gene template using
      two Escherichia coli RNA polymerases in a convergent transcription arrangement.
      Analysis of the AFM images indicates that the added loops have no effect on the
      ability of the promoters to recruit RNA polymerase. This labelling strategy is
      proposed as a generic methodology for end-labelling linear DNA for studying DNA
      protein interactions by AFM.

PMID- 22453276
TI  - The mechanics behind DNA sequence-dependent properties of the nucleosome.
AB  - Chromatin organization and composition impart sophisticated regulatory features
      critical to eukaryotic genomic function. Although DNA sequence-dependent histone
      octamer binding is important for nucleosome activity, many aspects of this
      phenomenon have remained elusive. We studied nucleosome structure and stability
      with diverse DNA sequences, including Widom 601 derivatives with the highest
      known octamer affinities, to establish a simple model behind the mechanics of
      sequence dependency. This uncovers the unique but unexpected role of TA
      dinucleotides and a propensity for G|C-rich sequence elements to conform
      energetically favourably at most locations around the histone octamer, which
      rationalizes G|C% as the most predictive factor for nucleosome occupancy in vivo.
      In addition, our findings reveal dominant constraints on double helix
      conformation by H3-H4 relative to H2A-H2B binding and DNA sequence context
      dependency underlying nucleosome structure, positioning and stability. This
      provides a basis for improved prediction of nucleosomal properties and the design
      of tailored DNA constructs for chromatin investigations.

PMID- 22453277
TI  - Fluorescence-based active site probes for profiling deubiquitinating enzymes.
AB  - Novel ubiquitin-based active site probes including a fluorescent tag have been
      developed and evaluated. A new, functionalizable electrophilic trap is utilized
      allowing for late stage diversification of the probe. Attachment of fluorescent
      dyes allowed direct detection of endogenous deubiquitinating enzyme (DUB)
      activities in cell extracts by in-gel fluorescence imaging.

PMID- 22453275
TI  - Mitochondrial nucleoid interacting proteins support mitochondrial protein
      synthesis.
AB  - Mitochondrial ribosomes and translation factors co-purify with mitochondrial
      nucleoids of human cells, based on affinity protein purification of tagged
      mitochondrial DNA binding proteins. Among the most frequently identified proteins
      were ATAD3 and prohibitin, which have been identified previously as nucleoid
      components, using a variety of methods. Both proteins are demonstrated to be
      required for mitochondrial protein synthesis in human cultured cells, and the
      major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3
      expression also perturbs mtDNA maintenance and replication. These findings
      suggest an intimate association between nucleoids and the machinery of protein
      synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the
      mitochondrial membranes and so we propose that they support nucleic acid
      complexes at the inner membrane of the mitochondrion.

PMID- 22453278
TI  - Peer review: the biomedical bowling league.

PMID- 22453279
TI  - A historical perspective on our understanding of the uterovaginal connective
      tissue supports.
AB  - OBJECTIVES: : The purpose of this research is to provide a historical perspective
      on the understanding of uterovaginal connective tissue supports. METHODS: :
      Articles were identified by a thorough review of the literature using electronic
      databases, and by reviewing references cited in articles and bibliographies of
      gynecologic textbooks. RESULTS: : Starting from the earliest written reports of
      connective tissue supports of the uterus and vagina, the development of this body
      of knowledge is reviewed chronologically. The works of those investigators who
      have made major contributions to our knowledge are highlighted. In particular,
      special attention is paid to Drs. Mackenrodt, Bonney, Richardson, DeLancey, and
      Petros/Ulmsten. CONCLUSIONS: : An appreciation of the early work by a few key
      pioneers in the 19th and early 20th centuries can enhance current understanding
      of the connective tissue supports of the uterus and vagina, and direct future
      research in urogynecology.

PMID- 22453280
TI  - Overactive bladder: correlating symptoms with low cystometric capacity.
AB  - OBJECTIVES: : Overactive bladder (OAB) is a symptom complex that may be
      objectively assessed using urodynamic variables. The purpose of this study was to
      determine the correlation between OAB symptoms and low cystometric capacity
      (LCC). METHODS: : Between October and December 2005, 102 patients from the
      Urogynaecology Clinic at Mount Sinai Hospital participated in this prospectively
      planned, blinded, cross-sectional study. Participants underwent multichannel
      urodynamic testing and completed a symptom questionnaire focusing on urinary
      urgency, frequency, and urgency incontinence, in addition to recording fluid and
      caffeine intake. Answers were combined into symptom complexes and dichotomized
      into positive and negative responses. The diagnostic accuracy of OAB symptoms was
      assessed by calculating sensitivity, specificity, likelihood ratios, positive and
      negative predictive values, and Cohen's kappa, using urodynamic bladder capacity
      <350 mL as the reference. RESULTS: : Fifty-seven percent (58) of participants met
      our urodynamic diagnosis of LCC with a bladder capacity <350 mL. Of the patients,
      49% (50) had a questionnaire result that was classified as positive for
      overactive bladder. The questionnaire had a specificity of 61%, a likelihood
      ratio of 1.47, a sensitivity of 57%, and a positive predictive value of 66%. With
      a Cohen's kappa = 0.2, there was poor reliability. Reanalysis using an
      alternative method of dichotomizing, a bladder capacity cut-off of <300 mL, and
      the addition of information regarding fluid intake, did not improve accuracy
      measures. CONCLUSIONS: : Symptom history of OAB does not correlate with low
      cystometric capacity. We need further research to determine the accuracy of
      subjective and objective findings in patients with OAB, to provide the most
      accurate diagnosis in the least invasive manner.

PMID- 22453281
TI  - The effect of voiding mechanism on success rates of midurethral sling procedures
      for stress urinary incontinence.
AB  - OBJECTIVE: : To evaluate the effect of voiding mechanism on cure rate of stress
      urinary incontinence in patients undergoing midurethral sling procedures.
      METHODS: : Retrospective study of 121 patients who underwent midurethral sling
      procedures (retropubic or transobturator [TO]) between January 2006 and October
      2007. Voiding mechanism was determined by preoperative pressure flow studies.
      Subjects were dichotomized to either "detrusor voiders" (N = 61) or "Valsalva
      voiders" (N = 60). Primary outcome was cure of stress urinary incontinence.
      RESULTS: : At a mean follow-up of 6.74 months, the overall success rate was 87.6%
      (85.7% for retropubic and 89.4% for TO). "Valsalva voiders" had a higher risk of
      failure compared with "detrusor voiders" (20% vs. 4.9%, respectively; OR = 4.83,
      95% CI: 1.29, 18.12, P = 0.012). This effect was significant for TO slings (P =
      0.025); however, sling type was not an independent predictor of failure.
      CONCLUSIONS: : Valsalva voiding mechanism is associated with an increased risk of
      failure of synthetic midurethral slings.

PMID- 22453282
TI  - Sacral neuromodulation outcomes in patients with urge urinary incontinence and
      concomitant urge fecal incontinence.
AB  - OBJECTIVES: : To study the efficacy and safety of sacral neuromodulation (SNM) in
      women with dual urge incontinence (DUI). METHODS: : Women with simultaneous urge
      urinary and urge fecal incontinence (FI) were prospectively identified and tested
      to determine eligibility for SNM. Those who experienced at least 50% improvement
      in their urinary symptoms were offered a full implant. Changes in FI were not
      considered. Validated questionnaires were administered at baseline and during
      follow-up. Preimplant urodynamic data were collected. Adverse events were
      recorded. RESULTS: : A total of 11 women had DUI. All had greater than 50%
      improvement in their urinary symptoms and underwent full implantation. Average
      age was 76 years. Median follow-up was 14 months. There were statistically
      significant improvements in validated questionnaire scores. No women were able to
      achieve complete simultaneous urinary and fecal continence. Six women (54%) were
      able to achieve at least a 50% improvement simultaneously in both their urinary
      and fecal symptoms. Two women (18%) only experienced a significant improvement in
      their urinary symptoms. One (9%) only experienced significant improvement in her
      FI. Two (18%) experienced no significant improvement in either their urinary or
      fecal symptoms. The urodynamic findings did not correlate with outcome. Two
      patients had transient implant pain. One implant was removed due to lack of
      efficacy at patient's request. CONCLUSIONS: : SNM is a safe and effective
      treatment for DUI. In patients with DUI, complete continence rates may be lower
      than with either type of incontinence alone. DUI may be the end-organ
      manifestations of a common neurologic pathway-overactive stimulation or
      underactive inhibition.

PMID- 22453283
TI  - Treatment of Vaginal Aplasia Among Afghan Women With the McIndoe Vaginoplasty.
AB  - OBJECTIVES: : The aim of this study was to evaluate the effectiveness of the
      McIndoe vaginoplasty for patients with vaginal aplasia in Afghanistan. MATERIALS
      AND METHODS: : This is a prospective study of 6 cases of vaginal aplasia which
      underwent McIndoe vaginoplasty over a period of 3 and one half years (2005-2008).
      RESULTS: : The McIndoe vaginoplasty was performed successfully in all 6 patients.
      Functional results were satisfactory. One patient developed a perineal laceration
      over 3 weeks post surgery, apparently from overzealous dilatation. No patient
      developed vaginal stenosis and all were capable of sexual function within 3
      months of the surgery. Postsurgical results were acceptable to the patients in
      all cases. CONCLUSION: : The McIndoe vaginoplasty is a safe and effective
      procedure for the treatment of vaginal aplasia, even in an austere surgical
      environment such as Afghanistan.

PMID- 22453284
TI  - Systemic effects of vaginally administered estrogen therapy: a review.
AB  - Hormone therapy was considered the standard of care before the publication of the
      Women's Health Initiative. After the study was published, the use of systemic
      hormone therapy dramatically decreased resulting in an increased incidence of
      menopausal symptoms such as hot flashes, vaginal dryness, and dyspareunia
      experienced by women. Use of vaginal estrogen offers women a unique alternative
      for relief of these symptoms. This article reviews the systemic effects of
      vaginally administered estrogen. Effects on serum hormone levels, vasomotor
      symptoms, lipid profiles, and use in women with breast cancer are reviewed. An
      accompanying review (J Pelvic Med Surg. 2009;15:105-114.) examines the local
      effects of vaginally administered estrogen.

PMID- 22453285
TI  - Case report of an appendiceal vaginal fistula following a mesh erosion.
AB  - This is the description of a 66-year-old woman, who had total abdominal
      hysterectomy and abdominal colposacropexy with mesh. Two and a half years later,
      she presented with infected mesh which was excised and then she developed an
      appendiceal vaginal fistula.

PMID- 22453286
TI  - The role of chaplains within oncology interdisciplinary teams.
AB  - PURPOSE OF REVIEW: The role of chaplains/spiritual care professionals and the
      importance of addressing spiritual needs within interdisciplinary oncology teams
      are in need of systematic review and critical appraisal. This review focuses on
      four key areas: basic concepts of spirituality within the healthcare domain; the
      relevance of spirituality within cancer care; the role of spiritual care within
      interdisciplinary cancer teams; and the current status of spiritual care
      professionals in interdisciplinary cancer teams. RECENT FINDINGS: Addressing
      cancer patient's spiritual issues is recognized as a component of comprehensive
      cancer care. Spirituality has a positive effect on subjective and emotional
      aspects of cancer patient's health, including quality of life, wellbeing and
      distress. Failing to address cancer patients spiritual needs impacts patient
      wellbeing, satisfaction with care, perceived quality of care and is associated
      with higher healthcare costs. Although a variety of disciplines address spiritual
      issues, spiritual care professionals are recognized by patients, clinicians,
      researchers and within best practice guidelines of national health councils as
      specialists within this domain. SUMMARY: Spiritual care professionals are
      increasingly recognized as integral members of interdisciplinary oncology teams.
      However, the full integration of spiritual care professionals within the standard
      practice of oncology interdisciplinary teams is lacking, as spiritual care
      services continue to be treated as ancillary services within cancer care
      organizations.

PMID- 22453287
TI  - Restoration and re-creation:  spirituality in the lives of healthcare
      professionals.
AB  - PURPOSE OF REVIEW: The clinician-patient relationship is essential to the
      practice of person-centered care. This healing relationship can present
      challenges to clinicians when working with patients who suffer. Clinicians today
      are looking for ways to deal with the stress of care-giving and to find greater
      meaning in their professional lives. RECENT FINDINGS: Professional guidelines
      recognize that medicine, nursing and other healthcare professions are vocations,
      not jobs. Reports indicate that physicians and other clinicians feel the current
      healthcare environment is too business-like yet, patient relationships continue
      to be the primary source of satisfaction for many clinicians. The relationships
      can be rewarding but also stressful. Spirituality is proposed as a way for
      clinicians to reconnect with their professional roots to serve those who suffer.
      Resources are suggested that might enable clinicians to find greater meaning in
      their profession. SUMMARY: Professional development should address spiritual
      development especially as it relates to the healthcare professional's sense of
      calling to their profession, the basis of relationship-centered care, and the
      provision of compassionate care.

PMID- 22453288
TI  - Evolving definitions of hope in oncology.
AB  - PURPOSE OF REVIEW: This review updates the literature on hope and oncology
      following a prior review of studies up until 2009. It particularly focusses on
      the evolution of the definition of hope in the light of the clinical experience
      of patients with cancer, their carers and health professionals. RECENT FINDINGS:
      Hope creates meaning for patients and is an important coping mechanism.
      Clinicians are wary of communicating bad news because it may deprive patients of
      hope, but work with decision aids suggests that this communication can be managed
      successfully. Hope and optimism negatively correlate with anxiety and depression.
      Maintaining hope may result in patients with incurable cancer accepting
      treatments or trials with little chance of benefit. Hope also needs to be
      maintained by palliative care nurses who harmonize their hopes with the different
      degrees and constructs of hope around them. Hope interventions can be successful
      in increasing hope and decreasing psychological distress. SUMMARY: More research
      is required into how to communicate about active anticancer treatment withdrawal
      and prognosis without depriving patients with cancer of hope, given how important
      hope is in alleviating psychological distress. The optimal intervention to
      increase levels of hope needs further investigation.

PMID- 22453290
TI  - Unravelling fears of genetic discrimination: an exploratory study of Dutch HCM
      families in an era of genetic non-discrimination acts.
AB  - Since the 1990s, many countries in Europe and the United States have enacted
      genetic non-discrimination legislation to prevent people from deferring genetic
      tests for fear that insurers or employers would discriminate against them based
      on that information. Although evidence for genetic discrimination exists, little
      is known about the origins and backgrounds of fears of discrimination and how it
      affects decisions for uptake of genetic testing. The aim of this article is to
      gain a better understanding of these fears and its possible impact on the uptake
      of testing by studying the case of hypertrophic cardiomyopathy (HCM). In a
      qualitative study, we followed six Dutch extended families involved in genetic
      testing for HCM for three-and-a-half years. Semi-structured interviews were
      conducted with 57 members of these families. Based on the narratives of the
      families, we suggest that fears of discrimination have to be situated in the
      broader social and life-course context of family and kin. We describe the
      processes in which families developed meaningful interpretations of genetic
      discrimination and how these interpretations affected family members' decisions
      to undergo genetic testing. Our findings show that fears of genetic
      discrimination do not so much stem from the opportunity of genetic testing but
      much more from earlier experiences of discrimination of diseased family members.
      These results help identify the possible limitations of genetic non
      discrimination regulations and provide direction to clinicians supporting their
      clients as they confront issues of genetic testing and genetic discrimination.

PMID- 22453291
TI  - Lactose malabsorption is a risk factor for decreased bone mineral density in
      pancreatic insufficient cystic fibrosis patients.
AB  - As decreased bone mineral density (BMD) is a common problem in cystic fibrosis
      (CF) and milk products may have pivotal dietary role affecting BMD, we aimed to
      assess the potential influence of adult-type hypolactasia (ATH) and lactose
      malabsorption (LM) on BMD in adolescent and young adult patients. In 95 CF
      pancreatic-insufficient patients aged 10-25 years (without liver cirrhosis,
      steatosis and cholestasis, diabetes mellitus, systemic glucocorticoid therapy),
      lumbar BMD, the nutritional status, pulmonary function, vitamin D3 concentration,
      calcium intake and single-nucleotide polymorphism upstream of the lactase gene
      were assessed. In subjects with the -13910 C/C genotype predisposing to ATH, the
      presence of LM was determined with the use of a hydrogen-methane breath test
      (BT). BMD and calcium intake were significantly lower in patients with the C/C
      genotype (P<0.028 and P<0.043, respectively). The abnormal BMD was stated more
      frequently in patients with the C/C genotype (P<0.042) and with LM (P<0.007).
      BMD, daily calcium intake and serum vitamin D concentration were significantly
      lower in LM subjects than in the other patients (P<0.037, P<0.000004 and
      P<0.0038, respectively). In logistic regression analysis, the relationship
      between examined parameters and BMD, was found to be statistically significant
      (P<0.001). However, only standardized body weight and LM were documented to
      influence BMD (P<0.025 and P<0.044, respectively). In conclusion, LM seems to be
      an independent risk factor for decreased BMD in CF patients.

PMID- 22453292
TI  - The changing landscape of genetic testing and its impact on clinical and
      laboratory services and research in Europe.
AB  - The arrival of new genetic technologies that allow efficient examination of the
      whole human genome (microarray, next-generation sequencing) will impact upon both
      laboratories (cytogenetic and molecular genetics in the first instance) and
      clinical/medical genetic services. The interpretation of analytical results in
      terms of their clinical relevance and the predicted health status poses a
      challenge to both laboratory and clinical geneticists, due to the wealth and
      complexity of the information obtained. There is a need to discuss how to best
      restructure the genetic services logistically and to determine the clinical
      utility of genetic testing so that patients can receive appropriate advice and
      genetic testing. To weigh up the questions and challenges of the new genetic
      technologies, the European Society of Human Genetics (ESHG) held a series of
      workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite
      symposium on the 'Changing landscape of genetic testing', co-organized by the
      ESHG Genetic Services Quality and Public and Professional Policy Committees. The
      audience consisted of a mix of geneticists, ethicists, social scientists and
      lawyers. In this paper, we summarize the discussions during the workshops and
      present some of the identified ways forward to improve and adapt the genetic
      services so that patients receive accurate and relevant information. This paper
      covers ethics, clinical utility, primary care, genetic services and the blurring
      boundaries between healthcare and research.

PMID- 22453289
TI  - Diabetic cardiomyopathy: pathophysiology and clinical features.
AB  - Since diabetic cardiomyopathy was first reported four decades ago, substantial
      information on its pathogenesis and clinical features has accumulated. In the
      heart, diabetes enhances fatty acid metabolism, suppresses glucose oxidation, and
      modifies intracellular signaling, leading to impairments in multiple steps of
      excitation-contraction coupling, inefficient energy production, and increased
      susceptibility to ischemia/reperfusion injury. Loss of normal microvessels and
      remodeling of the extracellular matrix are also involved in contractile
      dysfunction of diabetic hearts. Use of sensitive echocardiographic techniques
      (tissue Doppler imaging and strain rate imaging) and magnetic resonance
      spectroscopy enables detection of diabetic cardiomyopathy at an early stage, and
      a combination of the modalities allows differentiation of this type of
      cardiomyopathy from other organic heart diseases. Circumstantial evidence to date
      indicates that diabetic cardiomyopathy is a common but frequently unrecognized
      pathological process in asymptomatic diabetic patients. However, a strategy for
      prevention or treatment of diabetic cardiomyopathy to improve its prognosis has
      not yet been established. Here, we review both basic and clinical studies on
      diabetic cardiomyopathy and summarize problems remaining to be solved for
      improving management of this type of cardiomyopathy.

PMID- 22453293
TI  - Non-invasive prenatal diagnosis for fetal sex determination: benefits and
      disadvantages from the service users' perspective.
AB  - Prenatal fetal sex determination is clinically indicated for women who are at
      risk of having a child with a serious genetic disorder affecting a particular
      sex. Ultrasound has been the traditional method used, but early fetal sex
      determination using non-invasive prenatal diagnosis (NIPD) can now be performed
      using cell-free fetal DNA in maternal plasma. The study aim was to assess the
      views and experiences of service users who had used NIPD for fetal sex
      determination. In this paper, we report on the perceived benefits and
      disadvantages. A qualitative approach using semi-structured interviews was used.
      A total of 44 participants (38 women and 6 partners of participating women) were
      recruited. Participants' views and experiences of NIPD were overwhelmingly
      positive. Concerning benefits over traditional methods, three themes emerged: (1)
      technical aspects of technology; (2) timing; and (3) enhanced decision-making.
      Practical advantages of NIPD included avoiding miscarriage, and there were a
      number of psychological advantages associated with timing such as perceived
      control, early re-engagement, normalization of pregnancy and peace of mind.
      Participants also valued NIPD as it enabled a stepwise approach to decision
      making. A number of disadvantages were discussed including concerns about social
      sexing and increased bonding at a time in pregnancy when miscarriage risk is
      high. However, participants felt these were fairly minor in comparison with the
      advantages of NIPD. Until definitive genetic diagnosis using NIPD is available,
      NIPD for fetal sex determination is perceived as a good interim measure with a
      number of notable advantages over traditional methods.

PMID- 22453295
TI  - Small molecule semiconductors for high-efficiency organic photovoltaics.
AB  - Organic photovoltaic cells (OPVs) are a promising cost-effective alternative to
      silicon-based solar cells, and possess light-weight, low-cost, and flexibility
      advantages. Significant progress has been achieved in the development of novel
      photovoltaic materials and device structures in the last decade. Nowadays small
      molecular semiconductors for OPVs have attracted considerable attention, due to
      their advantages over their polymer counterparts, including well-defined
      molecular structure, definite molecular weight, and high purity without batch to
      batch variations. The highest power conversion efficiencies of OPVs based on
      small molecular donor/fullerene acceptors or polymeric donor/fullerene acceptors
      are up to 6.7% and 8.3%, respectively, and meanwhile nonfullerene acceptors have
      also exhibited some promising results. In this review we summarize the
      developments in small molecular donors, acceptors (fullerene derivatives and
      nonfullerene molecules), and donor-acceptor dyad systems for high-performance
      multilayer, bulk heterojunction, and single-component OPVs. We focus on
      correlations of molecular chemical structures with properties, such as
      absorption, energy levels, charge mobilities, and photovoltaic performances. This
      structure-property relationship analysis may guide rational structural design and
      evaluation of photovoltaic materials (253 references).

PMID- 22453294
TI  - Ethnic microaggressions and the depressive and somatic symptoms of Latino and
      Asian American adolescents.
AB  - Ethnic microaggressions are a form of everyday, interpersonal discrimination that
      are ambiguous and difficult to recognize as discrimination. This study examined
      the frequency and impact of microaggressions among Latino (n = 247) and Asian
      American (n = 113) adolescents (M (age) = 17.18, SD = .75; 57 % girls). Latino
      adolescents reported more frequent microaggressions that dismiss their realities
      of discrimination and microaggressions characterized by treatment as a second
      class citizen than Asian Americans, but similar levels of microaggressions that
      highlight differences or foreignness. There were no ethnic differences in the
      extent to which adolescents were bothered by microaggressions. Moreover, even
      supposedly innocuous forms of discrimination are associated with elevated levels
      of anxiety, anger, and stress, which may increase feelings of depression and
      sickness. Microaggressions should be recognized as subtle discrimination that
      send messages about group status and devaluation, and similar to overt
      discrimination, can evoke powerful emotional reactions and may affect mental
      health.

PMID- 22453296
TI  - Maternal weight and excessive weight gain during pregnancy modify the
      immunomodulatory potential of breast milk.
AB  - INTRODUCTION: Breast milk is an optimal source of nutrition for infants. It
      contains bioactive components including bacteria that support the microbial
      colonization and immune system development of the infant. The determinants of
      human milk composition remain poorly understood, although maternal nutritional
      and immunological status as well as lifestyle and dietary habits seem to have an
      impact. METHODS: The subjects selected were women from a prospective follow-up
      study categorized by BMI. Milk samples were taken after delivery and at 1 and 6
      mo later for analysis of composition in regard to transforming growth factor
      (TGF)-beta2, soluble CD14 (sCD14), cytokines, and microbiota. RESULTS: TGF-beta2
      and sCD14 levels in the breast milk of overweight mothers tended to be lower than
      the levels in that of normal-weight mothers. Also, higher levels of
      Staphylococcus group bacteria and lower levels of Bifidobacterium group bacteria
      were detected in overweight mothers as compared with normal-weight ones. The
      prevalence of Akkermansia muciniphila-type bacteria was also higher in overweight
      mothers, and the numbers of these bacteria were related to the interleukin (IL)-6
      concentration in the colostrum, which was in turn related to lower counts of
      Bifidobacterium group bacteria in the breast milk of overweight women.
      DISCUSSION: Complex interactions of cytokines and microbiota in breast milk guide
      the microbiological, immunological, and metabolic programming of infant health.
      Our data may indicate the presence of an additional mechanism that may explain
      the heightened risk of obesity for infants of overweight and excessive weight
      gain mothers.

PMID- 22453297
TI  - Fatal neonatal lactic acidosis caused by a novel de novo mitochondrial G7453A
      tRNA-Serine ((UCN)) mutation.
AB  - INTRODUCTION: Heteroplasmic mitochondrial DNA (mtDNA) mutations are an important
      cause of childhood disorders, but the role of homoplasmic mtDNA mutations in
      severe neonatal manifestations is not well understood. METHODS: The following
      were performed: full mtDNA sequencing for mutation detection, blue-native protein
      analysis of autopsy-derived tissues to detect respiratory chain (RC) deficiency,
      light and electron microscopy for morphologic analysis, and northern blot and
      computational modeling to study the effect of mtDNA mutations on transfer RNA
      (tRNA) stability. RESULTS: We describe data from a patient with fatal neonatal
      lactic acidosis caused by a novel homoplasmic mutation at a highly conserved
      nucleotide G7453A within the tRNA(Ser (UCN)) in mtDNA. The patient's heart,
      skeletal muscle, brain, and liver showed severe combined complex I and IV (CI and
      CIV) deficiencies, accompanied by severe depletion of mature tRNA(Ser (UCN)). The
      mutation was absent in the patient's mother and in a placental sample from a
      subsequent pregnancy of the mother, suggesting a de novo mutation. DISCUSSION: We
      conclude that the G7453A mutation of mtDNA manifests with exceptional severity as
      compared with other tRNA(Ser (UCN)) mutations, typically associated with
      sensorineural deafness. De novo homoplasmic mtDNA tRNA-mutations should be
      considered as a cause of fatal neonatal lactic acidosis.

PMID- 22453298
TI  - Do national advisories serve local consumers: an assessment of mercury in
      economically important North Carolina fish.
AB  - Consumption of marine fish provides both benefits (lean protein, omega-3 fatty
      acids and essential nutrients) and risks (main source of mercury (Hg) exposure
      for humans). Mercury is a potent neurotoxin and the source of more fish
      advisories nationwide than any other toxicant. Despite the widespread nature of
      Hg, it is unknown whether local Hg contamination reflects national and regional
      levels often used as bases to inform consumers of potential fish consumption
      risk. Thus, the objectives of our study were to examine Hg levels of six commonly
      consumed marine species harvested locally off the North Carolina coast and to
      compare our results to published regional (Monterey Bay Aquarium's Seafood Watch
      List) and national (Environmental Protection Agency, EPA, and Food and Drug
      Administration, FDA) Hg averages, action levels, and guidelines. We found
      significant differences in Hg concentrations among collected species, and we
      identified correlations between Hg concentration and fish length and trophic
      levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action
      level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below
      the FDA action level (1.0ppm). King mackerel had the highest Hg concentration
      among targeted species, exceeding both EPA and FDA action levels. Further, our
      local results were not always consistent with calculated averages from EPA and
      FDA databases for the same species, and although many of our findings were
      consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region),
      recommendations based on Hg levels would conflict with recommendations they
      provide based on sustainability. We find regional and national averages are not
      always reflective of local Hg contamination and suggest local data may be needed
      to accurately assess consumer risk.

PMID- 22453299
TI  - Effects of post-traumatic stress disorder on occipital lobe function and
      structure.
AB  - Although there is evidence for strong connectivity between the amygdala and the
      visual cortex and some evidence for reduced occipital lobe gray matter volume in
      patients with post-traumatic stress disorder (PTSD), few studies have directly
      examined the effects of PTSD on occipital function. The current study used
      functional and structural MRI to examine occipital cortex function and structure
      in male combat veterans with and without PTSD. Left occipital gray matter volume
      was reduced in PTSD patients relative to the controls and correlated negatively
      with the severity of PTSD symptoms. Functional activity in the lateral occipital
      complex to aversive and nonaversive pictures presented in novel and repeated
      presentations was not altered by PTSD. These findings suggest that PTSD adversely
      affects occipital lobe volume but not the reactivity of the lateral occipital
      complex to generally aversive, trauma nonspecific stimuli.

PMID- 22453300
TI  - Transretinal ERG recordings from mouse retina: rod and cone photoresponses.
AB  - There are two distinct classes of image-forming photoreceptors in the vertebrate
      retina: rods and cones. Rods are able to detect single photons of light whereas
      cones operate continuously under rapidly changing bright light conditions.
      Absorption of light by rod- and cone-specific visual pigments in the outer
      segments of photoreceptors triggers a phototransduction cascade that eventually
      leads to closure of cyclic nucleotide-gated channels on the plasma membrane and
      cell hyperpolarization. This light-induced change in membrane current and
      potential can be registered as a photoresponse, by either classical suction
      electrode recording technique or by transretinal electroretinogram recordings
      (ERG) from isolated retinas with pharmacologically blocked postsynaptic response
      components. The latter method allows drug-accessible long-lasting recordings from
      mouse photoreceptors and is particularly useful for obtaining stable
      photoresponses from the scarce and fragile mouse cones. In the case of cones,
      such experiments can be performed both in dark-adapted conditions and following
      intense illumination that bleaches essentially all visual pigment, to monitor the
      process of cone photosensitivity recovery during dark adaptation. In this video,
      we will show how to perform rod- and M/L-cone-driven transretinal recordings from
      dark-adapted mouse retina. Rod recordings will be carried out using retina of
      wild type (C57Bl/6) mice. For simplicity, cone recordings will be obtained from
      genetically modified rod transducin alpha-subunit knockout (Talpha(-/-)) mice
      which lack rod signaling(8).

PMID- 22453301
TI  - Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in
      natto, a Japanese traditional fermented food.
AB  - Angiotensin I converting enzyme (ACE) was inhibited by the culture medium of
      Bacillus subtilis subsp. natto, which ferments boiled soy beans to natto, a
      Japanese traditional food. Subtilisin NAT (nattokinase) produced by B. subtilis
      also inhibited ACE, and the inhibition was markedly stimulated by heat treatment
      of subtilisin at 120  degrees C for 15 min. Inhibition of ACE by subtilisin was
      of a mixed type: the decrease in V(max) and the increase in K(m) value. SDS
      polyacrylamide gel electrophoresis showed that heat treatment of subtilisin
      caused inactivation with fragmentation of the enzyme protein into small peptides.
      The inhibitory action of subtilisin was not due to an enzymatic action of
      protease, but may be ascribed to the potent ACE-inhibitory peptides such as LY
      and FY, amino acid sequences in subtilisin. HPLC-MS analysis of heat-inactivated
      subtilisin confirmed that LY and FY were liberated by fragmentation of the
      enzyme. Inhibition of ACE by subtilisin and its degradation peptides such as LY
      and FY may participate in the suppression of blood pressure by ingestion of
      natto.

PMID- 22453302
TI  - Metastatic carcinoma in the ulna of a cat secondary to a suspected pulmonary
      tumour.
AB  - A 14-year-old male neutered Burmese cat presented for investigation of right fore
      limb lameness that was non-responsive to anti-inflammatory drugs and opioids.
      Thoracic radiography showed multiple pulmonary soft tissue nodules and a larger
      cavitated mass. Right elbow radiographs revealed marked peri-articular
      proliferation of new bone and periosteal reaction primarily affecting the ulna.
      Histopathological examination of an incisional biopsy of the right ulna revealed
      neoplastic proliferation of epithelial cells; this was confirmed as a poorly
      differentiated carcinoma with immunohistochemistry. Amputation of the right fore
      limb was performed at the owner's request. After surgery, radiographs of the limb
      showed progression of bone proliferation. Repeat pathological analysis confirmed
      a metastatic carcinoma. The cat deteriorated 3 days after surgery and was
      euthanased a week later as a result of severe respiratory distress. This case
      represents an unusual case of metastasis of a suspected primary lung tumour to
      the ulna in a Burmese cat.

PMID- 22453303
TI  - Ultrasound-guided block of the feline sciatic nerve.
AB  - This study was conducted to validate an ultrasound-guided technique to block the
      sciatic nerve in cats. An anatomical study was first carried out in four feline
      cadavers to evaluate the feasibility of the glutea (cranial and caudal), femoris
      and poplitea ultrasonographical approaches for the sciatic nerve block. The
      results showed that the femoris approach was optimal because the region was free
      of vascular and bony structures, and the needle was easily visualised in-plane.
      Then, the efficacy of the femoris ultrasonographical approach to block the
      sciatic nerve was tested in six healthy adult experimental cats. A dose of 2
      mg/kg lidocaine 2% diluted in saline to a final volume of 1 ml was administered
      in all cats. The blockade was successful in all cases and the cats recovered
      uneventfully. This study shows the usefulness of the femoris approach in
      performing an ultrasound-guided blockade of the sciatic nerve in cats.

PMID- 22453304
TI  - ABL1 deletion without BCR/ABL1 rearrangement is originated from a large-sized 9q
      deletion.

PMID- 22453305
TI  - Hereditary thrombocythemia caused by a thrombopoietin (THPO) gain-of-function
      mutation associated with multiple myeloma and congenital limb defects.
AB  - Hereditary thrombocythemia (HT) has been described as a rare benign disorder
      caused by mutations in the thrombopoietin (THPO) or the c-Mpl receptor genes.
      Here we report two families with HT resulting from a THPO c.13+1 G>C mutation in
      the splice donor of intron 3. In one family there were coexisting distal limb
      defects, whereas in the other one member developed early-onset multiple myeloma.
      These observations, together with previously reported patients, suggest that THPO
      gain of function may dysregulate the hemangioblast and disturb vasculogenesis and
      hematopoietic development. Overstimulation of the THPO pathway might therefore
      predispose to clonal hematopoietic disease and to congenital abnormalities.

PMID- 22453306
TI  - Characterization of immunoglobulin lambda light chain variable region (IGLV) gene
      and its relationship with clinical features in patients with POEMS syndrome.
AB  - The M protein of POEMS syndrome is essentially lambda light chain restricted.
      Several studies have demonstrated the restrict usage of immunoglobulin lambda
      light chain variable region (IGLV) genes in patients with POEMS syndrome.
      However, these studies only included a limited number of cases, and it is not
      clear whether the clinical features are influenced by the IGLV gene in POEMS
      syndrome. Here we demonstrated that the clonal IGLV genes were strictly derived
      from IGLV 1-40 (11 patients, 36.7 %) and IGLV 1-44 (19, 63.3 %) gene in 30
      patients with POEMS syndrome. We further evaluated the relationship between
      clinical features and IGLV genes. Our study showed that patients with IGLV 1-44
      were older than those with IGLV 1-40, and patients with IGLV 1-40 had more severe
      neuropathy, hypertrichosis, and papilledema. It was suggested that the IGLV gene
      influenced clinical characteristics in POEMS syndrome.

PMID- 22453307
TI  - Effect of compression therapy on knee swelling and pain after total knee
      arthroplasty.
AB  - PURPOSE: Knee swelling after total knee arthroplasty may impair postoperative
      mobilisation and training, and as medical elastic compression stockings are well
      tolerated and effective to prevent oedema, haematoma and postoperative pain after
      venous surgery, we wanted to study whether this effect could be transferred to
      total knee arthroplasty surgery reducing postoperative swelling and pain and
      thereby facilitating mobilisation and improving patient-reported knee function.
      METHODS: In a randomised controlled study, 88 patients were randomised to use
      either a medical elastic compression stocking or no stocking from the first
      postoperative day and the following 4 weeks after total knee arthroplasty.
      Outcome measures were knee, calf and ankle swelling, knee flexion, pain and
      patient-reported knee function. RESULTS: Seventy per cent of the swelling had
      occurred before application of the stocking the day after surgery. Knee, calf and
      ankle swelling and knee flexion measured on days 2, 7, 14 and 30 showed no
      significant difference between the two groups. Maximum pain level at rest and at
      walking was similar for both groups during the observation period. Also, the
      Oxford knee score was similar between the two groups on days 14 and 30.
      CONCLUSION: We did not find any clinical effect using a medical elastic
      compression stocking after total knee arthroplasty. LEVEL OF EVIDENCE: I.

PMID- 22453308
TI  - Intraarticular local anesthetics: primum non nocere.

PMID- 22453309
TI  - Variability of gait parameters in patients with total knee arthroplasty.
AB  - PURPOSE: Gait analysis has provided important information about the variability
      of gait for patients prior to and after total knee arthroplasty (TKA). The
      objective of this research was to clarify how the different surgical techniques
      influence gait variability. METHODS: Gait analysis was performed at 0.8, 1.0, and
      1.2 m/s in three groups of patients (operated on using the conventional
      technique, conventional technique combined with computer-assisted navigation, and
      the minimally invasive technique combined with computer-assisted navigation; n =
      15 each) and a control group (n = 15; healthy, age, body mass, and body height
      matched). Gait analysis was performed preoperatively and 6 and 12 months after
      the surgery. Gait parameter variability was characterized by the coefficient of
      variance of spatio-temporal parameters and by the mean coefficient of variance of
      angular parameters. RESULTS: One year after surgery, the variability of spatio
      temporal parameters recovered to normal in patients operated on using the
      conventional technique; however, the variability of articular motion of the
      affected side decreased and the variability of articular motion of the non
      affected side and pelvis increased compared to the control group. In patients
      operated on using the minimally invasive technique, the variability of spatio
      temporal and angular parameters was similar to that of the control group.
      CONCLUSION: The type of surgical technique significantly influences the
      variability and stability of gait. Difference in the variability of angular
      parameters predicts gait instability and increased risk of falling after TKA with
      the conventional surgical technique. The minimally invasive technique ensures a
      recovery of gait variability and stability. Thus, particular attention must be
      paid to improving gait stability during postoperative rehabilitation. LEVEL OF
      EVIDENCE: II.

PMID- 22453310
TI  - Knee arthroplasty and bleeding: when to remove drainages.
AB  - PURPOSE: The aim of this study is an attempt to clarify the productive time of
      drainages as we find that the use of drains in knee arthroplasty is
      controversial, and there is no consensus regarding their length-time maintenance.
      We analysed the survival curve of bleeding within three surgical techniques for
      knee arthroplasty and the effect of two variables on survival curve. METHODS: One
      hundred and eighty-eight out of 234 knees were included in the study, and
      patients were divided into three groups according to the surgical technique:
      conventional total knee arthroplasty (TKA), subvastus TKA and unicompartmental
      knee arthroplasty. Variables of study were type of surgery, number and placement
      of drains. RESULTS: Mean of survival curve for postoperative bleeding time was 16
      h (95 % CI: 15.4; 16.6). The risk for longer bleeding increased 1.38-fold with
      each additional drain used (95 % CI 1.1; 1.8). CONCLUSIONS: According to the
      present study, drains can be safely removed at around 17 h postoperative.
      Bleeding time reduces as less drains are applied. LEVEL OF EVIDENCE: Therapeutic
      study, Level III.

PMID- 22453312
TI  - Palpation tests versus impingement tests in Neer stage I and II subacromial
      impingement syndrome.
AB  - PURPOSE: Using sonographic findings to test the diagnostic accuracy of
      impingement versus tendon palpation tests in Neer stage I and II subacromial
      impingement syndrome cases and examine their clinical potential. METHODS: Neer
      and Hawkins impingement tests and rotator cuff tendon palpation tests followed by
      bilateral shoulder sonography were conducted on 69 patients with a clinical
      diagnosis of unilateral subacromial impingement. RESULTS: The Neer and Hawkins
      tests had 74 and 62 % accuracy (sensitivity 80 and 67 %, and specificity 52 and
      47 %, respectively) in comparison to 79 and 62 % accuracy rates for supraspinatus
      and biceps tendon palpation tests (sensitivity 92 and 41 %, and specificity 41
      and 48 %, respectively). Overall, the palpation tests scored better than
      impingement tests in the diagnosis of Neer stage I and II subacromial impingement
      syndrome. No tendinosis or tear was noted in patients with negative findings in
      the supraspinatus palpation tests (sensitivity 100 %, specificity 21 %).
      CONCLUSION: Palpation tests for supraspinatus and biceps tendons have a slightly
      higher accuracy than the impingement tests, and if tenderness does not exist then
      supraspinatus tendinopathy can be ruled out. These findings warrant the use of
      palpation tests in a routine physical examination for tendinopathy. LEVEL OF
      EVIDENCE: I.

PMID- 22453313
TI  - So what am I supposed to do in the or monday morning?

PMID- 22453314
TI  - Urogenital fistula.
AB  - This review summarizes the available evidence in the literature on the etiology,
      diagnosis, management, and prevention of vesicovaginal, urethrovaginal,
      ureterovaginal, vesicocervical, and vesicouterine fistulae. Urogenital fistula is
      divided by origin: obstetric fistula occurring predominantly in developing
      countries and iatrogenic fistula, the most common cause in developed countries.

PMID- 22453315
TI  - Conflicts-of-interest disclosures at the 2010 AUGS Scientific Meeting.
AB  - OBJECTIVES: To describe authors' trends in reporting conflicts of interest in
      their research at the 2010 Annual Scientific Meeting of the American
      Urogynecologic Society. METHODS: We extracted data regarding financial
      disclosures during oral presentations and compared the conflicts of interest
      disclosed during oral presentations with those enumerated in the published
      abstract. RESULTS: We collected data on 86 of 100 oral presentations given at the
      2010 American Urogynecologic Society scientific meeting. Seventy-five (87%) of
      the 86 presentations included a disclosure slide. Twenty-six of the 86 presenters
      had no verbal mention of potential conflicts of interest. There was discordance
      between disclosures printed in the abstract and those listed in the oral
      presentation in 49% of the papers, with slides providing more comprehensive
      information in 64% of the entries. CONCLUSIONS: Despite instructions to the
      contrary, 13% of presentations in 2010 did not address potential influence by a
      financial subsidy. Explicit instructions, a streamlined reporting process, and
      prioritization by our scientific community may improve the consistency and
      uniformity of financial disclosure reporting.

PMID- 22453316
TI  - Bowel function after minimally invasive urogynecologic surgery:  a prospective
      randomized controlled trial.
AB  - OBJECTIVES: The goals of this study were to assess the effect of a standardized
      postoperative bowel regimen of over-the-counter medications on (1) time to first
      bowel movement (BM) and (2) pain level associated with first BM in subjects
      undergoing minimally invasive urogynecologic surgery. METHODS: Eligible patients
      scheduled to undergo minimally invasive urogynecologic surgery were offered
      participation. Enrolled subjects were randomized by computerized schedule.
      Demographic and perioperative data were collected. Subjects completed a validated
      questionnaire preoperatively and postoperatively assessing preexisting
      constipation, frequency and consistency of bowel movements, use of pain
      medications, mean daily pain level (using visual analog scale), stool
      consistency, and pain associated with first postoperative bowel movement. The
      control group was instructed to take docusate sodium twice daily postoperatively.
      The treatment group took docusate sodium plus Miralax, fiber wafers, and
      bisacodyl suppositories as directed by protocol. Wilcoxon or t testing was used
      to compare continuous variables; chi testing was used for categorical
      relationships, and backward-elimination multiple regression was used to assess
      independent effects. RESULTS: Seventy-two subjects were enrolled and randomized.
      Twelve subjects withdrew, leaving 60 (30 per group) completing the study. There
      were no statistically significant differences between groups in baseline
      characteristics. Mean (SD) age was 63 (9) years for the control group and 58 (10)
      for the study group (P = 0.06). Mean pelvic organ prolapse stage was III in each
      group. The mean (SD) operating room time was 198 (65) minutes for the controls
      and 216 (74) for the study subjects. Sixty-five percent underwent robot-assisted
      surgery (50% hysterectomy and 63% sacrocolpopexy). Ninety-eight percent of
      surgeries were performed under general anesthesia.Before adjustment, the mean
      (SD) time to first BM was 77 (24) hours in controls versus 64 (21) in the study
      patients (P = 0.03). Using multiple regression, baseline frequency of defecation
      (1-2 BMs/wk) was directly associated with the time to first BM (added 25.2 hours;
      P = 0.009) and being in the study group was inversely associated (first BM, 11.7
      hours sooner; P = 0.04). No other variables were retained.There was no difference
      in pain associated with first postoperative BM (visual analog scale, 3.6 (3.2) vs
      3.7 (2.8); P = 0.98), but those with prior complaints of vaginal or rectal
      splinting had higher pain scores (1.9 and 2.8 points higher, respectively; P =
      0.04 for both). There was a trend toward higher pain scores with higher
      postoperative daily narcotic intake (P = 0.06). No other variables were
      retained.There was a significant difference in recorded compliance between
      control versus study regimens (94% vs 81%, respectively; P = 0.002). CONCLUSIONS:
      Mean time to first postoperative BM after minimally invasive urogynecologic
      surgery is more than 3.5 days with use of docusate sodium alone and is only
      slightly shorter when combination therapy is used. First BM after surgery is
      considered to be painful despite the use of medications. Future studies targeting
      postoperative discomfort/pain with defecation could target preoperative bowel
      regimens or more aggressive postoperative interventions. Regimens should remain
      simple to increase compliance.

PMID- 22453317
TI  - Mesh erosion in robotic sacrocolpopexy.
AB  - OBJECTIVE: This study aimed to compare the incidence of mesh erosion after
      robotic sacrocolpopexy between women undergoing total and those undergoing
      supracervical hysterectomy (SH). METHODS: This is a retrospective cohort study of
      women who underwent sacrocolpopexy and concomitant hysterectomy using the DaVinci
      surgical robot between May 2007 and December 2010 at 2 sites. Baseline data were
      gathered before surgery. The primary outcome was mesh erosion identified during 3
      months of follow-up. RESULTS: A total of 102 women underwent sacrocolpopexy, of
      whom 45 were with concomitant SH and 57 were with total hysterectomy (TH). Their
      mean age was 58 years, mean body mass index was 26.8 kg/m, 98% were white, 6%
      smoked, and 25% were on systemic hormone replacement therapy. Mean preoperative
      Ba = +1.4, C = -2.2. These were not different between the 2 groups or by site.
      Within 3 months of surgery, mesh erosion was diagnosed in 8 women, all of whom
      had TH. No mesh erosions occurred in the SH group (14% vs 0%). Total hysterectomy
      mesh erosion rate at site 1 was 37% compared with 3% [corrected] at site 2. Mesh
      type was the only identifiable difference between sites: self-cut polypropylene
      at site 1, precut polypropylene at site 2. Two women in the SH had abnormal
      uterine pathology: 1 endometrial adenocarcinoma and 1 focus of hyperplasia with
      atypia. CONCLUSIONS: No mesh erosions were associated with SH within the first 3
      months. In TH, the graft material used may be a modifiable factor needing further
      investigation. Unexpected abnormal uterine pathologic diagnosis remains a
      possibility with SH. Longer-term follow-up and a randomized trial are warranted
      to answer these questions.

PMID- 22453318
TI  - Institutional review board variability in minimal-risk multicenter urogynecology
      studies.
AB  - OBJECTIVES: To investigate variability among local institutional review boards
      (IRBs) in the review process of standardized multicenter urogynecologic studies
      with common protocols. METHODS: Descriptive study of the IRB review and approval
      process for common urogynecologic protocols of 4 minimal-risk multicenter studies
      conducted within the Fellow's Pelvic Research Network (FPRN), including
      prospective cohort, retrospective review, and case-control studies. RESULTS: Most
      of the 22 network sites (73%) were in academic institutions. The level of IRB
      review varied by site and study design. Institutional review boards had local
      requirements regarding standard format and language that resulted in 86% of
      consent documents and 33% of protocols being changed before submission.
      Institutional review boards queried most (55%) submissions, with significantly
      more queries for prospective studies compared to retrospective studies (78.6% vs
      35.3%; P = 0.03). After submission, IRB requirements necessitated changes for 71%
      of consents and 28% of protocols. There were no substantive changes made to any
      consent document or protocol. There was considerable variability in time between
      IRB submission and approval (10 +/- 3 days; range, 7-12 days for exempt; 22 +/-
      17 days; range, 1-57 days for expedited; and 34 +/- 32 days; range, 13-81 days
      for full board reviews). CONCLUSIONS: We detected considerable variability in IRB
      review of standardized multicenter protocols across minimal-risk study designs.
      Reduction in variability may improve expediency of multicenter studies while
      maintaining the highest level of protections for research participants.

PMID- 22453319
TI  - A randomized comparison of bupivacaine versus saline during placement of tension
      free vaginal tape.
AB  - OBJECTIVES: To compare postoperative urinary retention and pain control when
      bupivacaine versus saline for hydrodissection is used while placing tension-free
      vaginal tape midurethral slings. METHODS: A prospective, randomized, double-blind
      trial was performed after institutional review board approval. Sixty women were
      randomized to receive bupivacaine or saline for hydrodissection. Subjects and
      research team were blinded to subject assignments. Group characteristics were
      compared using the Student t test, the chi test, and the Mann-Whitney U test.
      Proportions of subjects with a successful postoperative voiding trial along with
      measurements of postoperative pain and analgesic use were compared using similar
      appropriate tests. The study was powered to detect differences in voiding trial
      success from an estimated 58% to greater than 90% with P < 0.05 and 0.8 power
      using 25 subjects per group. RESULTS: Thirty patients were allocated to each
      group. One subject in the saline-only group was excluded. Group characteristics
      were not different. After surgery, pain medication use (20/30 vs 25/29 for
      bupivacaine vs saline only; P = 0.08), pain scores (36 +/- 22 vs 31 +/- 24; P =
      0.49), and successful voiding trials did not differ (14/30 vs 19/29; P = 0.14),
      whereas postvoid residuals did differ (225 +/- 180 mL vs 140 +/- 147 mL; P =
      0.043). CONCLUSIONS: Bupivacaine was not seen to improve immediate postoperative
      pain after placement of a tension-free vaginal tape. It did not increase the risk
      of failing a postoperative voiding trial. Without an obvious benefit, the use of
      an additional medicine is not supported. We suggest saline alone be used for
      hydrodissection.

PMID- 22453320
TI  - Reported cystoscopic experience correlates poorly with objective assessment of
      cystoscopic skills.
AB  - OBJECTIVE: Although gynecologists perform a large number of surgeries in close
      proximity to the ureters and the urinary bladder, traditionally, Obstetrics and
      Gynecology resident physicians are not formally taught to perform cystoscopy. The
      primary objective was to document resident physicians' performance in diagnostic
      cystoscopic instrumentation and technique. The secondary objective was to examine
      if reported prior cystoscopic experience was associated with superior
      performance. METHODS: Fifty-one postgraduate year 4 residents with reported
      experience with cystoscopy were evaluated using an operation-specific checklist
      and a global ratings scale based on the Objective Structured Assessment of
      Technical Skill model. Before evaluation, they attended a formal training session
      in cystoscopy, which included practice on a bench model of a simulated bladder.
      RESULTS: Forty-three of the 51 residents were able to successfully perform a
      thorough diagnostic examination immediately after the course. Six of the 8
      failures were re-evaluated 2 weeks later and successfully performed a complete
      examination at that time. Before the course, the residents had performed a mean
      of 12.2 cystoscopic examinations as the primary surgeon (median, 12; range, 2
      33). The number of reported cystoscopic examinations performed before the course
      did not correlate with the ability to perform a thorough cystoscopic examination
      (r = -0.109; P = 0.496). CONCLUSIONS: For this group of residents, there was poor
      correlation between the number of reported cystoscopic examinations and the
      ability to perform diagnostic cystoscopy. Trainees may not be able to determine
      when they have received enough instruction in hands-on training with models
      before acquisition of technical skills.

PMID- 22453321
TI  - Quality of life is markedly improved in patients with fecal incontinence after
      sacral nerve stimulation.
AB  - OBJECTIVE: The aim of the present analysis was to report on the relationship
      between long-term improvement in quality of life (QOL) and fecal incontinence
      (FI) severity and long-term reduction in FI episodes after sacral nerve
      stimulation (SNS) or sacral neuromodulation. METHODS: Patients who met
      inclusion/exclusion criteria, and initially had more than 2 FI episodes per week,
      were offered SNS therapy. Patients with 50% or higher reduction in FI during a 2
      week test period were implanted with a neurostimulator (InterStim; Medtronic,
      Minneapolis, Minn). Assessments were completed by patients at baseline and at 3,
      6, and 12 months after implant, and annually thereafter. The present report
      includes data from the 4-year postimplant follow-up. RESULTS: A total of 133
      patients underwent test stimulation with a 90% success rate, and as a result, 120
      (110 females) with a mean age of 60.5 years and a mean duration of FI of 6.8
      years received long-term implantation. Of them, 78 patients completed all or part
      of the 4-year follow-up assessment. Fecal incontinence episodes decreased from a
      mean of 9.4 per week at baseline to 1.9 per week at 48 months (P < 0.001). The 4
      year analyses showed that SNS had a positive and sustained impact on all 4 scales
      of the Fecal Incontinence Quality of Life questionnaire (P < 0.001), Fecal
      Incontinence Severity Index scores improved from a mean of 39.9 to 28 (P <
      0.001), and self-rated bowel health scores improved from a mean of 3.5 to 6.9 (P
      < 0.001). CONCLUSIONS: Sacral nerve stimulation not only restores or improves
      continence in treated patients with chronic FI but also improves their quality of
      life and symptom severity.

PMID- 22453322
TI  - Effect of operative technique on mesh exposure in laparoscopic sacrocolpopexy.
AB  - OBJECTIVES: To determine if opening the vaginal cuff during laparoscopic
      sacrocolpopexy influences the rate of mesh exposure. METHODS: A total of 390
      medical records were retrospectively reviewed for demographic information,
      operative technique, and relevant outcomes. RESULTS: Eleven mesh exposures (2.8%)
      and 14 suture extrusions (3.6%) were found, none involving visceral organs. Mesh
      exposure was more common when the vaginal cuff was opened, either during
      hysterectomy or when allowing transvaginal attachment of mesh in patients with a
      prior hysterectomy (4.9% vs 0.5%; relative risk [RR], 9.0, P = 0.012). In cases
      where concomitant hysterectomy was performed, a higher mesh exposure rate was
      seen in open-cuff hysterectomy (total vaginal hysterectomy/laparoscopically
      assisted vaginal hysterectomy) compared to supracervical hysterectomy (4.9%
      [9/185] vs 0% [0/92]; P = 0.032). Mesh exposure was more common when the mesh was
      sutured laparoscopically compared with transvaginally in patients undergoing open
      cuff hysterectomy (14.3% [5/35] vs 2.7% [4/150]; RR, 5.4; P = 0.013). Permanent
      suture extrusion was significantly associated with laparoscopic versus
      transvaginal suturing of mesh (5.6% vs 0.6%; RR, 8.8; P = 0.010). Five patients
      underwent reoperation for mesh exposure, whereas most suture extrusions were
      asymptomatic; and all were managed nonsurgically. CONCLUSIONS: We found that
      preserving the integrity of the vaginal cuff led to a lower incidence of mesh
      exposure in patients undergoing laparoscopic sacrocolpopexy. When hysterectomy is
      indicated, a supracervical technique should be strongly considered as the mesh
      exposure rate was significantly lower. If removal of the cervix is indicated, the
      risk for mesh exposure remains low and should not preclude total hysterectomy,
      though transvaginal mesh attachment may be preferable.

PMID- 22453323
TI  - Pelvic floor symptoms improve similarly after pessary and behavioral treatment
      for stress incontinence.
AB  - OBJECTIVE: The objective of this study was to determine if differences exist in
      pelvic symptom distress and impact on women randomized to pessary versus
      behavioral therapy for treatment of stress urinary incontinence (SUI). METHODS:
      Change in symptom and condition-specific health-related quality-of-life (HRQOL)
      measures were compared between pessary and behavioral groups 3 months after
      randomization in the Ambulatory Treatments for Leakage Associated With Stress
      Incontinence trial. Four hundred forty-six women with symptoms of SUI were
      randomized to continence pessary, behavioral therapy (pelvic floor muscle
      training and continence strategies) or combination therapy. Validated measures
      utilized included urinary, prolapse, and colorectal scales of the Pelvic Floor
      Distress Inventory; urinary, prolapse, and colorectal scales of the Pelvic Floor
      Impact Questionnaire; and Stress and Urge scales of the Questionnaire for Urinary
      Incontinence Diagnosis. Student t test and analysis of variance were used to
      compare scores within and between groups. RESULTS: Mean age of participants was
      49.8 (SD, 11.9) years; 84% were white, and 10% were African American. One hundred
      forty-nine were randomized to pessary, and 146 to behavioral therapy. Baseline
      symptoms and HRQOL scores were significantly reduced within treatment arms at 3
      months after randomization, but there was no statistically significant difference
      between groups. CONCLUSIONS: There was no difference in pelvic floor symptom
      bother and HRQOL between the pessary and behavioral therapy arms in women
      undergoing conservative treatment for SUI. Individualized preference issues
      should be considered in the approach to the nonsurgical treatment of SUI.

PMID- 22453324
TI  - Minimally invasive apical sacropexy:  a retrospective review of laparoscopic and
      robotic operating room experiences.
AB  - OBJECTIVES: Minimally invasive apical sacropexies (MI-APSC) can be performed
      using robotics or laparoscopy. We hypothesized that operative characteristics of
      MI-APSC, laparoscopic (LSC) and robotic (RSC), were similar. The objective of our
      study was to compare operative characteristics, objective prolapse outcomes, and
      robotic learning curve. METHODS: Ninety-two women planning MI-APSC for treatment
      of apical pelvic organ prolapse from 2006 to 2010 were included in the study. The
      primary outcome was operative time. The secondary outcomes included estimated
      blood loss, rate of conversion, intraoperative complications, hospital stay, and
      objective prolapse outcome. We also analyzed the robotic learning curve.
      Statistical analysis included independent samples t test, Wilcoxon rank sum test,
      chi, and multiple logistic regressions; significance was set at P < 0.05.
      Learning curve was graphed with moving average and analyzed with moving block
      technique. RESULTS: Forty-eight RSCs and 43 LSCs were analyzed. Mean operative
      times were LSC, 238 +/- 59 minutes; and RSC, 242 +/- 54 minutes. Robotic MI-APSC
      setup was longer (P = 0.02). Complications, conversions, estimated blood loss and
      hospital stay were low and similar between groups. Patients' characteristics were
      similar. Concomitant procedures produced longer operative times. CONCLUSIONS:
      Operating room experiences with laparoscopic- and robotic-assisted approaches to
      MI-APSC were similar, but setup time is longer for the robotic-assisted approach.
      The robotic learning curve is short for surgeons who have experience with LSC.

PMID- 22453325
TI  - Sacral nerve stimulation during pregnancy:  case report and review of the
      literature.
AB  - BACKGROUND: The use of sacral nerve stimulation during pregnancy is not
      recommended because of the unknown effects on the offspring. There is a paucity
      of literature on the subject. CASE: A 25-year-old woman who had a sacral nerve
      stimulator for severe interstitial cystitis/bladder pain syndrome had 2
      successful pregnancies. Against medical advice, she kept the stimulator activated
      for symptom control during the pregnancies. The first child was later diagnosed
      with chronic motor tic disorder, and the second had a pilonidal sinus at birth.
      Whether this outcome is related to the neurostimulator is unknown. The efficacy
      of sacral nerve stimulation decreased after each pregnancy. CONCLUSION: The
      safety of sacral nerve stimulation in pregnancy has not been well established.
      Until further research is done, we recommend that women of reproductive age with
      a sacral nerve stimulator be advised about contraception and that the device
      should be deactivated before or as soon as pregnancy is confirmed.

PMID- 22453326
TI  - Unrecognized bladder perforation leading to severe progressive cellulitis and
      candidal infection.
AB  - BACKGROUND: Retropubic midurethral slings are a minimally invasive surgical
      procedure used in the treatment of stress urinary incontinence and are typically
      associated with high cure rates and low complication rates. Bladder perforation
      is a known intraoperative complication that, if left unrecognized, can have
      significant morbidity. CASE: A 47-year-old underwent a retropubic midurethral
      sling, anterior colporrhaphy, and cystoscopy. She developed a suprapubic wound
      cellulitis that progressed to involve the right trunk and flank as well as
      persistent fever for more than 48 hours despite broad-spectrum antibiotics. Upon
      return to the operating room, the patient was found to have an unrecognized
      bladder perforation with mesh in the bladder. Wound culture was remarkable for
      Candida parapsilosis and Escherichia coli. CONCLUSION: Unrecognized bladder
      perforation and nonbacterial causes of infection should be considered in patients
      with severe progressing cellulitis despite broad-spectrum antibiotic coverage
      after retropubic midurethral sling placement.

PMID- 22453327
TI  - Urethral injury with transobturator midurethral sling.
AB  - Transobturator midurethral slings were introduced to avoid retropubic
      complications such as bladder, urethra, bowel, and major vessel injuries.
      However, complications are not completely eliminated. We present a urethral
      injury presenting with urge predominant mixed incontinence. The sling was removed
      transvaginally. Urethral injuries are now less common than they originally were
      owing to advances in operative technique and product innovation. However, it is
      incumbent on physicians to evaluate product characteristics that may affect
      outcomes in their patients. We further reiterate that thorough cystoscopy with
      urethroscopy is an essential step when performing transobturator midurethral
      slings.

PMID- 22453328
TI  - Medical home disparities for children by insurance type and state of residence.
AB  - The objectives of this study are (1) to compare the prevalence of a medical home
      between children with public and private insurance across states, (2) to
      investigate the association between a medical home and state health care
      characteristics for children with public and private insurance. We performed a
      cross-sectional analysis of the 2007 National Survey of Children's Health,
      estimating the prevalence of parents' report of a medical home and its components
      for publicly- and privately-insured children in all 50 states and the District of
      Columbia. We then performed a series of random-effects multilevel logistic
      regression models to assess the associations between a medical home and insurance
      type, individual sociodemographic characteristics, and state level
      characteristics/policies. The prevalence of a medical home varied significantly
      across states for both publicly- and privately-insured children (ranges: 33-63 %
      and 57-76 %, respectively). Compared to privately-insured children, publicly
      insured children had a lower prevalence of a medical home in all states (public
      private difference: 5-34 %). Low prevalence of a medical home was driven
      primarily by less family-centered care. Variation across states and differences
      by insurance type were largely attributable to lower reports of a medical home
      among traditionally vulnerable groups of children, including racial/ethnic
      minorities and non-English primary language speakers. The prevalence of a medical
      home was not associated with state level characteristics/policies. There are
      significant disparities between states in parents' report of a medical home for
      their children, especially for publicly-insured children. Interventions seeking
      to address these disparities will need to target family-centered care for
      traditionally vulnerable populations of children.

PMID- 22453329
TI  - Biases in studying gestational weight gain and infant mortality in US birth
      certificates.

PMID- 22453330
TI  - Characteristics of children eligible for public health insurance but uninsured:
      data from the 2007 National Survey of Children's Health.
AB  - To describe the state variation, demographic and family characteristics of
      children eligible for public health insurance but uninsured. Using data from the
      National Survey of Children's Health we selected a subset of children living in
      households with incomes <200 % of the federal poverty level, who are generally
      eligible for Medicaid or CHIP. We used multiple logistic regression to examine
      associations between insurance status among this group of eligible children and
      certain demographic factors, family characteristics, and state of residence. In
      adjusted models children aged 6-11 and 12-17 years were more likely to be
      eligible but uninsured compared to those aged 0-5 years (AOR 1.57; 95 % CI 1.15
      2.16 and AOR 1.93; 95 % CI 1.41-2.64). Children who received school lunch (AOR
      0.67; 95 % CI 0.52-0.86) and SNAP (AOR 0.33; 95 % CI 0.24-0.46) were less likely
      to be eligible but uninsured compared to those children not receiving those needs
      based services; however, a majority (58.7 %) of eligible uninsured children were
      enrolled in the school lunch program. Five states (Texas, California, Florida,
      Georgia, New York) accounted for 46 % of the eligible uninsured children. Vermont
      had the lowest adjusted estimate of eligible uninsured children (3.6 %) and
      Nevada had the highest adjusted estimate (35.5 %). Using nationally
      representative data we have identified specific state differences, demographic
      and household characteristics that could help guide federal and local initiatives
      to improve public health insurance enrollment for children who are eligible but
      uninsured.

PMID- 22453331
TI  - Child, family, and neighborhood associations with parent and peer interactive
      play during early childhood.
AB  - To examine national patterns of peer and parent interactive play opportunities
      that enhance early learning/socialization. Bivariate and multivariable analyses
      of cross-sectional data on 22,797 children aged 1-5 years from the National
      Survey of Children's Health 2007 were performed to determine the child, family,
      and neighborhood factors associated with four parent-initiated activities.
      Outcomes measures included time (days/week) children spent: participating in peer
      play; being read to; sung to/told stories; and taken on family outings.
      Covariates included race/ethnicity, poverty, TV watching, childcare, child and
      maternal physical and mental health, family factors (structure, size, language,
      stress, education), and neighborhood factors (amenities, support, physical
      condition, safety). According to adjusted regression models, minority children
      from lower income, non-English-speaking households with limited education, poorer
      maternal health and greater parenting stress were read to/told stories less than
      children without these characteristics, while neighborhood factors exerted less
      influence. In contrast, significant reductions in days/week of peer play were
      associated with unsupportive neighborhoods and those with the poorest physical
      conditions and limited amenities. Likewise, reductions in outings were associated
      with fewer neighborhood amenities. The findings of this study indicate that a
      variety of child, family, and neighborhood factors are associated with parent
      initiated behaviors such as reading, storytelling, peer interactive play, and
      family outings. Appropriate evidence-based home visiting interventions targeting
      child health, parenting skills, early childhood education, and social services in
      at-risk communities would appear to be appropriate vehicles for addressing such
      parent-initiated play activities that have the potential to enhance development.

PMID- 22453332
TI  - Inter-state variation in human papilloma virus vaccine coverage among adolescent
      girls in the 50 US states, 2007.
AB  - Human papilloma virus (HPV) vaccination could substantially reduce the burden of
      cervical cancer by preventing HPV infection. This study uses the 2007 National
      Survey of Children's Health (NSCH) to estimate HPV vaccine coverage prevalence
      for US girls aged 12-17, the target group for vaccination. NSCH is a population
      based telephone survey of households with children younger than 18 years. The
      proportion of girls aged 12-17 whose parent or guardian reported receipt of a
      clinician recommendation for HPV vaccination, one or more does of HPV vaccine, or
      a complete three-dose HPV vaccine series were estimated. Multivariable models
      estimated adjusted associations and marginal predicted vaccine coverage
      prevalence for each of the 50 US states and according to race/ethnicity,
      household income, insurance status, parental education, and whether the girl had
      a 'medical home'. The NSCH sample included 17,264 girls aged 12-17. Overall 18.2
      % (SE 0.8 %) of girls reportedly received at least one HPV vaccine dose and 3.6 %
      (SE 0.4 %) completed the series; 31 % received clinician recommendation for HPV
      vaccine. Girls who received a clinician recommendation to vaccinate were 23 (95 %
      CI 18-29) times as likely to be vaccinated as those not counseled. There was
      substantial interstate variation in vaccine coverage that was largely explained
      by variability in clinician counseling. For 2007, there was substantial variation
      in HPV vaccine coverage among US girls 12-17 years that was largely explained by
      variability in clinician counseling. Strategies aimed at increasing clinicians'
      counseling for HPV vaccination could substantially reduce disparities in HPV
      vaccine coverage.

PMID- 22453333
TI  - The Prostate cancer Research International: Active Surveillance study.
AB  - PURPOSE OF REVIEW: To inform readers on the ongoing activities of the Prostate
      cancer Research International: Active Surveillance (PRIAS) study in the light of
      current findings and research problems on active surveillance worldwide. RECENT
      FINDINGS: Recent data from the PRIAS study combined with PubMed-based literature
      from the last 3 years. SUMMARY: The PRIAS study is a rapidly growing registry for
      active surveillance of low-risk prostate cancer. The study is conducted
      worldwide, facilitated by an electronic Web-based decision tool with password
      restricted access for physicians. Inclusion and monitoring is performed according
      to protocol. Over 2000 men have been included from over 100 participating centres
      in 17 countries in four continents. The study was initiated in December 2006.
      Risk reclassification on repeat biopsy during follow-up has occurred in 27% of
      biopsied men, although a switch towards active therapy has been performed in 22%
      of the total cohort.

PMID- 22453334
TI  - Radiation-based approaches for therapy and palliation of advanced prostate
      cancer.
AB  - PURPOSE OF REVIEW: Randomized clinical trials of palliative radiation therapy and
      radiopharmaceuticals are emphasized, and new concepts in targeted alpha-emitter
      therapy are introduced. RECENT FINDINGS: Radiation therapy has a proven
      palliative role in the treatment of patients with advanced prostate cancer.
      Findings from 223radium clinical trials emphasize the importance of alpha
      particles as a new therapeutic modality in patients with bone metastatic castrate
      resistant prostate cancer. We introduce the concept of alpha-emitting particles
      from both a basic and clinical perspective in the realm of bone-targeted
      radiopharmaceuticals and discuss how these agents compare and contrast with
      conventional beta-emitting radioisotopes. The physics, radiobiology, and survival
      data with 223radium are unique compared with previously used
      radiopharmaceuticals. SUMMARY: Targeted alpha-emitting therapies such as
      223radium have the capacity to change the way we treat patients with bone
      metastatic prostate cancer.

PMID- 22453335
TI  - Active surveillance:  the Canadian experience.
AB  - PURPOSE OF REVIEW: Active surveillance has evolved to become a standard of care
      for favorable-risk prostate cancer. This article is a summary of the rationale,
      method, and results of active surveillance beginning in 1995 with the first
      prospective trial of this approach. RECENT FINDINGS: This was a prospective,
      single arm cohort study. Patients were managed with an initial expectant
      approach. Definitive intervention was offered to those patients with a prostate
      specific antigen (PSA) doubling time of less than 3 years, Gleason score
      progression (to 4 + 3 or greater), or unequivocal clinical progression. Since
      November 1995, 450 patients have been managed with active surveillance. Median
      follow-up is 6.8 years (range 1-16 years). Overall survival is 78.6%. Ten-year
      prostate cancer actuarial survival is 97.2%. Five of 450 patients (1.1%) have
      died of prostate cancer. Thirty percent of patients have been reclassified as
      higher risk and offered definitive therapy. The commonest indication for
      treatment was a PSA doubling time less than 3 years (48%) or Gleason upgrading
      (26%). Of 117 patients treated radically, the PSA failure rate was 50%. This
      represents 13% of the total cohort. Most PSA failures occurred early; at 2 years,
      44% of the treated patients had PSA failure. The hazard ratio for nonprostate
      cancer to prostate cancer mortality was 18.6 at 10 years. SUMMARY: We observed a
      very low rate of prostate cancer mortality in an intermediate time frame. Among
      the one-third of patients who were reclassified as higher risk and retreated, PSA
      failure was relatively common. However, other cause mortality accounted for
      almost all of the deaths. Further studies are warranted to improve the
      identification of patients who harbor more aggressive disease in spite of
      favorable clinical parameters at diagnosis.

PMID- 22453336
TI  - Treatment of basilar tip aneurysms with horizontal PCA to PCA stent-assisted
      coiling: case series.
AB  - BACKGROUND AND OBJECTIVE: Coiling of wide-necked basilar tip aneurysms is
      technically challenging and is often assisted by the placement of a stent. Stent
      placement in an anterograde fashion either with a single or Y-stent is typical.
      However, in some cases the posterior cerebral artery (PCA) angle of origin at the
      base of the aneurysm precludes anterograde catheterization. A series of patients
      with wide-necked basilar tip aneurysms treated with a single stent placed via the
      posterior communicating artery from PCA to PCA is presented. METHODS: A
      retrospective database review was performed to identify all stent-coiled basilar
      tip aneurysms. Patients with attempted horizontal P1-P1 stenting via the
      posterior communicating artery were identified. Procedural imaging, follow-up
      angiography and clinical notes were reviewed. RESULTS: P1-P1 stenting was
      attempted in 10 patients and was successful in eight. Angiographic follow-up was
      available in six patients, all of whom had >90% obliteration at last follow-up.
      There was one procedure-related subarachnoid hemorrhage that resulted in patient
      death. There were no cases of significant PCA stenosis on angiographic follow-up.
      CONCLUSIONS: This stenting technique is an effective way to treat wide-necked
      basilar tip aneurysms but is limited by the anatomy of the posterior
      communicating arteries and P1 segments.

PMID- 22453337
TI  - CyclinD2 at the edge: splitting up cell fate.

PMID- 22453338
TI  - Structure of a dominant-negative helix-loop-helix transcriptional regulator
      suggests mechanisms of autoinhibition.
AB  - Helix-loop-helix (HLH) family transcription factors regulate numerous
      developmental and homeostatic processes. Dominant-negative HLH (dnHLH) proteins
      lack DNA-binding ability and capture basic HLH (bHLH) transcription factors to
      inhibit cellular differentiation and enhance cell proliferation and motility,
      thus participating in patho-physiological processes. We report the first
      structure of a free-standing human dnHLH protein, HHM (Human homologue of murine
      maternal Id-like molecule). HHM adopts a V-shaped conformation, with N-terminal
      and C-terminal five-helix bundles connected by the HLH region. In striking
      contrast to the common HLH, the HLH region in HHM is extended, with its
      hydrophobic dimerization interfaces embedded in the N- and C-terminal helix
      bundles. Biochemical and physicochemical analyses revealed that HHM exists in
      slow equilibrium between this V-shaped form and the partially unfolded, relaxed
      form. The latter form is readily available for interactions with its target bHLH
      transcription factors. Mutations disrupting the interactions in the V-shaped form
      compromised the target transcription factor specificity and accelerated myogenic
      cell differentiation. Therefore, the V-shaped form of HHM may represent an
      autoinhibited state, and the dynamic conformational equilibrium may control the
      target specificity.

PMID- 22453340
TI  - Pelvic organ prolapse: defining the disease.

PMID- 22453339
TI  - The demise of a TUDOR under stress opens a chromatin link to 53BP1.

PMID- 22453341
TI  - Consensus Statement on the Adoption of the COPE Guidelines.

PMID- 22453342
TI  - Allogenic myoblast transplantation in the rat anal sphincter.
AB  - OBJECTIVES: : To determine the feasibility of injecting rat myoblasts into the
      intact anal sphincter as a potential treatment for anal incontinence, and to
      detect transferred myoblast survival and integration. STUDY DESIGN: : A pilot
      study using nonpregnant female Sprague Dawley rodents of 8 to 10 weeks of age. A
      biopsy of skeletal muscle was harvested from a study animal and recovered
      myoblasts were expanded in vitro over 10 days. Myoblasts were then tagged with a
      cytomegalovirus promoter to transduce green fluorescent protein (GFP) into the
      myoblasts. The cell aspirate was injected directly into the intact external anal
      sphincter using an electromyographic guidance. The animals received 1.5 or 4.5 *
      10 cells of GFP-labeled myoblasts, dividing the dose between three injection
      sites. The remaining in vitro myoblasts were still viable 28 days post-harvest.
      Ten days after transplantation the anal sphincter complex was surgically
      extracted. RESULTS: : The presence of GFP-labeled myoblasts was confirmed within
      the external anal sphincter. CONCLUSIONS: : This demonstrates that myoblasts can
      be successfully extracted, cultivated in vitro, transplanted and will integrate
      into the host tissue.

PMID- 22453343
TI  - Functional bowel disorders and pelvic organ prolapse: a case-control study.
AB  - OBJECTIVES: : To compare the relative frequencies of constipation and other
      functional bowel disorders between patients with and without pelvic organ
      prolapse (POP). METHODS: : This was a case-control study design. Cases were
      patients with stage 3-4 POP presenting to a urogynecology clinic and controls
      were patients presenting to a general gynecology or women's health clinic for
      annual examinations with stage 0-1 vaginal support. Constipation disorders were
      defined using responses to the Rome II Modular Questionnaire for functional bowel
      disorders as well as predefined defecatory disorders. RESULTS: : 128 cases and
      127 controls were enrolled. After controlling for race, education, and
      comorbidities, women with POP were more likely to report symptoms consistent with
      outlet constipation, including straining during a bowel movement (odds ratio [OR]
      3.9, confidence interval [CI] 2.1-7.3), feeling of incomplete rectal emptying (OR
      4.0, CI 2.1-7.7), a sensation that stool cannot be passed (OR 3.4, CI 1.7-6.7),
      and splinting (OR 2.7, CI 1.3-5.7). In spite of this, cases were just as likely
      to meet the criteria for functional constipation or irritable bowel syndrome
      (IBS) with constipation as controls but more likely to meet the criteria for IBS
      any type (OR 3.8, CI 1.6-9.1) as women with POP reported more discomfort or pain
      in the abdomen (OR 3.4 CI 1.6-7.1) and >3 bowel movements per day (OR 2.9, CI 1.3
      6.3). CONCLUSIONS: : Patients with POP are more likely to have symptoms of outlet
      constipation and other functional bowel disorders compared with patients without
      POP. The Rome II criteria may not be an appropriate classification system for
      functional bowel disorders in patients with advanced POP.

PMID- 22453344
TI  - Urodynamic prediction of occult stress urinary incontinence before vaginal
      surgery for advanced pelvic organ prolapse: evaluation of postoperative outcomes.
AB  - OBJECTIVES: : To evaluate the use of urodynamics for assessment of occult stress
      urinary incontinence (SUI) in women undergoing vaginal surgery for advanced
      pelvic organ prolapse (POP). METHODS: : Retrospective chart review of women who
      underwent vaginal surgery for advanced POP at the University of Rochester Medical
      Center. RESULTS: : The study sample was composed of 41 women (mean age: 65.6
      years; range: 42-88 years). Prolapse was stage 3 or 4 in 40 (97.6%) women.
      Urodynamics identified 17 (41.5%) women with occult SUI. Postoperatively, 3
      (7.3%) women reported urinary incontinence: 1 with stress and 2 with urge-related
      symptoms. The woman with postoperative SUI had been diagnosed with occult SUI,
      but declined continence repair. None of the women without occult SUI on
      urodynamics reported postoperative SUI. CONCLUSIONS: : Urodynamic evaluation
      prior to vaginal surgery for advanced POP can identify women at risk for SUI, who
      may benefit from concomitant continence repair.

PMID- 22453345
TI  - A Valid Form of the PISQ-12, the PISQ-9, for Use in Comparative Studies of Women
      With and Without Pelvic Organ Prolapse and/or Urinary Incontinence.
AB  - OBJECTIVES: : To test the validity and reliability of a modified short-form
      Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-9) in a
      general female population. METHODS: : A cross-sectional survey of 364 sexually
      active women attending annual gatherings in 2005-06 was conducted. Validated
      questionnaires were completed, including PISQ-12, Index of Female Sexual Function
      (IFSF), Pelvic Floor Distress Inventory-20 (PFDI-20), Beck Depression Inventory
      Second Edition (BDI-II) and Pelvic Pain Urgency/Frequency (PUF) scale. PISQ
      12/PISQ-9 scores, for construct validity, were compared with the validated
      questionnaires, and reliability was assessed with Cronbach's alpha statistic.
      RESULTS: : PISQ-12/PISQ-9 scores correlated significantly with IFSF scores
      (Spearman-coefficient, 0.65 and 0.66, respectively, P < 0.0001). Mean PISQ
      12/PISQ-9 scores in asymptomatic women were significantly better than those in
      symptomatic women (PISQ-12: 40.0 +/- 4.3 versus 37.1 +/- 5.2, P < 0.0001; effect
      size = 0.65, PISQ-9: 28.1 +/- 4.1 versus 25.8 +/- 4.8, P < 0.0001, effect size =
      0.56). PISQ-12/PISQ-9 scores were worse in women with depressive/bladder-pain
      symptoms compared with those women without these symptoms. Cronbach's alpha
      values were 0.73 and 0.72 for PISQ-12 and PISQ-9 scores, respectively.
      CONCLUSIONS: : PISQ-9 scores strongly correlate with PISQ-12 scores as well as
      scores of a general sexual-function questionnaire and Cronbach's alpha statistics
      are acceptable. The PISQ-9 can be reliably used in comparative studies assessing
      pelvic floor function in women with and without prolapse or incontinence.

PMID- 22453346
TI  - A randomized trial to estimate the effect of an interactive computer trainer on
      resident knowledge of female pelvic floor dysfunction and anatomy.
AB  - OBJECTIVES: : To estimate the effect of a computer trainer on improving knowledge
      and attitudes of Obstetrics and Gynecology residents regarding female pelvic
      anatomy (PA) and pelvic floor dysfunction (PFD) compared to usual teaching.
      METHODS: : A randomized trial was conducted between April and June 2008.
      Obstetrics and Gynecology residents randomized by year of training participated
      in a 1-hour session with a computer trainer for individual-based learning of
      female PA and PFD or usual teaching. Questionnaires assessing (1) knowledge of
      and (2) attitude regarding, or comfort with, female PA and PFD were completed at
      baseline and 1 month following recruitment. Residents randomized to the trainer
      answered trainer-specific questions on the post-intervention questionnaire.
      Higher scores indicated higher knowledge and comfort level. Between-group
      differences in pre-intervention and post-intervention questionnaire knowledge and
      attitude scores were analyzed. Eleven residents randomized to each group would
      provide a power of 0.8 at alpha = 0.05. RESULTS: : Twenty-two residents completed
      the study. There were no significant differences between residents randomized to
      trainer versus usual teaching in knowledge or attitude scores on the pre
      intervention questionnaire (p > 0.50). There was no significant difference in
      median post-intervention knowledge (14 [range 13-17] vs 13 [range 10-18], P =
      0.10) or attitude scores (30 [range 14-41] vs 22 [range 11-42], P = 0.49) for the
      residents randomized to the trainer compared to the controls. CONCLUSIONS: : In
      this single-center study, the trainer was not associated with significant
      improvements in resident knowledge or attitude scores regarding female PA and
      PFD.

PMID- 22453347
TI  - Effect of suture selection on the rate of suture or mesh erosion and surgery
      failure in abdominal sacrocolpopexy.
AB  - OBJECTIVE: : To determine if suture type used for mesh attachment in abdominal
      sacrocolpopexy increases the rate of erosion/infection. METHODS: : Two groups
      were temporally divided from June 1996 to May 2001 where braided permanent
      sutures (2-0 Ethibond, Ethicon, Somerville, New Jersey) were exclusively used for
      graft placement (n = 161) and from August 2001 to May 2006 where exclusively
      monofilament delayed absorbable (2-0 PDS, Ethicon) was used (n = 254). Data were
      analyzed for demographics, medical history, presenting/postoperative physical
      examination, concomitant surgeries, and complications. RESULTS: : Mesh/suture
      exposure rate was 3.7% (6/161) with Ethibond. There were no erosions with PDS (P
      = 0.002). Colpopexy failure was 1.7% (2/116) with Ethibond and 0% (0/235) with
      PDS (P = 0.11). CONCLUSIONS: : Delayed absorbable, monofilament suture appears to
      reduce the risk of graft/suture erosion without increasing surgical failure.

PMID- 22453348
TI  - Long-term impact of abdominal sacral colpoperineopexy on symptoms of obstructed
      defecation.
AB  - OBJECTIVE: : To determine the long-term impact of abdominal sacral
      colpoperineopexy on symptoms of obstructed defecation. METHODS: : This is a long
      term retrospective cohort study. We included women who underwent abdominal sacral
      colpoperineopexy at our institution between 2001 and 2005. We compared
      preoperative and postoperative symptoms using the Pelvic Floor Distress Inventory
      Short Form 20. Postoperative status was assessed on a mailed postal
      questionnaire. Obstructed defecation was defined using items from the colorectal
      anal obstructive subscale. We also assessed patient satisfaction. Descriptive
      statistics were computed using standard methods for mean, median and proportions.
      RESULTS: : The study includes 38 women (21 completed both preoperative and
      postoperative questionnaires). Of 27 women completing the postoperative
      questionnaire at a median follow-up of 65 months (range 35-90 months), 23 (85%)
      reported obstructed defecatory symptoms and 12 (52%) reported bothersome
      symptoms. Sixty-three percent were satisfied with the results of their surgery.
      CONCLUSIONS: : Abdominal sacral colpoperineopexy is unlikely to eliminate
      symptoms of obstructed defecation, although two-thirds of the participants remain
      satisfied with their surgery at 5 years.

PMID- 22453349
TI  - Outcomes of Retropubic Synthetic Midurethral Gynecare TVT Slings When Performed
      by Urogynecologists, Urologists, and General Gynecologists in a Private Community
      Hospital.
AB  - OBJECTIVES: : To compare perioperative outcomes of a retropubic synthetic
      midurethral Gynecare TVT slings (Gynecare Worldwide, division of Ethicon Inc, NJ)
      performed by urogynecologists, urologists, and general gynecologists. METHODS: :
      This is a retrospective, cohort study of retropubic synthetic midurethral
      Gynecare TVT sling outcomes performed between 2001 and 2007 at a single
      institution. Other synthetic and nonsynthetic slings, or slings performed with
      concurrent surgeries were excluded. The primary outcomes were mean sling
      operating room (OR) time in minutes (min) and estimated blood loss in milliliters
      (mL). All variables were stratified by the surgeon's specialty: urogynecology
      (URO-GYN), urology (URO), and general gynecology (GYN). RESULTS: : Of 279
      Gynecare TVT sling procedures, 126 were performed by URO-GYN, 30 by URO, and 123
      by GYN. Mean sling OR time was 38.8 +/- 8.5 minutes for URO-GYN, 42.6 +/- 11.2
      minutes for URO, and 39.8 +/- 14.3 minutes for GYN, P = 0.30. Estimated blood
      loss was 56.6 +/- 68.3 mL for URO-GYN, 69.7 +/- 82.6 mL for URO, and 68.8 +/-
      73.4 mL for GYN, P = 0.37. The intraoperative complications (bladder, urethral
      perforations, and hemorrhage) were similar among the specialties. In the
      postoperative period, there was no difference in subsequent need for urethrolysis
      (cutting or removal of the sling), return to OR, and readmission to the hospital
      after the procedure among all 3 specialties. CONCLUSIONS: : All 3 specialties
      (urogynecologist, urologists, and general gynecologists) had similar major
      perioperative outcomes in performing retropubic synthetic midurethral Gynecare
      TVT slings.

PMID- 22453350
TI  - Reference lines in dynamic magnetic resonance imaging of the pelvic floor.
AB  - OBJECTIVE: : To compare the variability in two commonly used reference lines in
      pelvic magnetic resonance imaging (MRI), the pubococcygeal line (PCL) and the
      sacrococcygeal to inferior pubis (SCIPP) line, with respect to their distance
      from pelvic floor points of interest. METHODS: : We obtained pelvic MR images of
      20 asymptomatic nulliparous women who are part of an ongoing pelvic floor nerve
      injury postpartum study. The subjects underwent a high-resolution two
      dimensional, T2-weighted sagittal pelvic MRI in the supine position using a GE
      Signa scanner with a body phased-array coil. We also obtained dynamic T2-weighted
      sagittal MR images in supine position during Kegel and Valsalva maneuvers. Using
      the midsagittal image, we measured the length of two reference lines: the PCL and
      the more cephalad SCIPP line. From each line, we then measured the perpendicular
      distance to the bladder neck and to the posterior margin of the anorectal angle
      (M-line). We compared the mean values of all measurements between the two
      reference lines with paired Student t tests. RESULT: : The SCIPP line (mean [SD],
      11.60 [0.91] cm) is longer than the PCL (mean [SD], 10.54 [0.85] cm) at rest (P <
      0.001). There is no significant change in length from resting to Kegel maneuver
      or from resting to Valsalva maneuver in either reference line. Only the resting
      to Valsalva maneuver for the M-line was significantly different between the 2
      reference lines (P = 0.02). The resting to Kegel for the perpendicular distance
      to the bladder neck and the M-line was not significantly different between the
      two lines. CONCLUSIONS: : Both reference lines remain stable during pelvic floor
      maneuvers.

PMID- 22453351
TI  - A randomized trial of secondary closure of superficial wound dehiscence by
      surgical tape or suture.
AB  - OBJECTIVE: : Evaluate secondary closure of superficial wound dehiscence with
      suture versus tape. METHODS: : Postoperative obstetrics and gynecologic patients
      with superficial wound dehiscence were eligible. Wounds were opened for their
      entire length, debrided, and irrigated. They were packed with moistened gauze
      until the granulation tissue covered the wound. Randomization occurred when the
      patient selected a sealed envelope containing a closure technique. Demographic
      data and wound characteristics were recorded. Pain was determined by using a 100
      mm visual analogue scale, which the patient marked immediately after the
      procedure. Wound closure was measured in minutes. Healing time was measured in
      days from wound closure to complete wound epithelialization and no need for
      further wound care. Reopening a closed wound defined treatment failure. Time for
      complete healing was the primary outcome. RESULTS: : Fifteen patients were
      randomized to each arm over a 20-month period. Demographics and wound
      characteristics were similar between groups. Pain scores were significantly less
      in the tape group (21.4 +/- 17.0 vs 60.7 +/- 23.0 mm, P < 0.001) as was time for
      closure (12.3 +/- 3.6 vs 31.0 +/- 6.8 minutes, P < 0.001). Time for complete
      healing was significantly less in the suture group (23.0 +/- 7.9 vs 16.1 +/- 3.36
      days, P < 0.001). One wound (7%) in each group was reopened. CONCLUSIONS: :
      Suture closure seems to be the superior technique for secondary closure of wound
      dehiscence based on the primary outcome of time to complete healing for this
      study. Therefore, suture closure seems to be the best option for secondary
      closure of superficial wound dehiscence.However, both suture and surgical tape
      are effective treatments when historically compared with second intention.

PMID- 22453352
TI  - Sacral neuromodulation for nonobstructive urinary retention: a meta-analysis.
AB  - OBJECTIVE: : The objective of this study is to systematically review the
      literature regarding the efficacy of sacral neuromodulation (InterStim) for
      treatment of nonobstructive urinary retention. METHODS: : Eligible studies were
      selected through an electronic literature search of PubMed, Cochrane
      Collaboration, EMBASE, Web of Science and Scopus databases from January 1980 to
      August 2008. Two investigators independently reviewed all studies to assess
      methodological quality and inclusion criteria. Eligible studies evaluated sacral
      neuromodulation using implanted generators with permanent lead placement for
      treating nonobstructive urinary retention. The primary outcomes assessed were the
      change in pre- and postoperative postvoid residual and voided volume. Exclusion
      criteria were neurogenic etiology (ie, spinal cord injury) for urinary retention
      and non-English studies. The lead authors of all selected studies were contacted
      to identify ongoing or unpublished research, as was Medtronic, Inc. (Minneapolis,
      MN). Data were extracted from the selected studies and analyzed using RevMan 5
      (Review Manager, Cochrane Collaboration, 2008). The mean difference with a 95%
      confidence interval was the effect of interest. RESULTS: : A total of 14 articles
      met all inclusion criteria for the systematic review. This included one
      randomized control trial (RCT) and 13 observational studies. Outcome data was
      available from a total of 7 studies and used in the final analysis. After
      implantation, the mean difference in postvoid residual decreased 236 mL (95% CI:
      219-253, P < 0.00001) and voided volume increased by 299 mL (95% CI: 280-318, P <
      0.00001). The randomized control trial alone (n = 51) showed a mean decrease in
      postvoid residual volume in the implanted group compared with control of 270 mL
      (95% CI: 180-360, P < 0.00001) and a mean increase in voided volume of 104 mL
      (95% CI: 55-152, P < 0.0002). CONCLUSIONS: : Based on the available literature,
      sacral neuromodulation is an effective therapy for treatment of nonobstructive
      urinary retention.

PMID- 22453353
TI  - Combinatorial topography and cell-type specific regulation of the ERK pathway by
      dopaminergic agonists in the mouse striatum.
AB  - Therapeutic agents and drugs of abuse regulate the extracellular signal-regulated
      kinase (ERK) cascade signaling in the medium-sized spiny neurons (MSNs) of the
      striatum. However, whether this regulation is associated with specific cortical
      and thalamic inputs has never been studied. We used Drd2-EGFP BAC-transgenic mice
      to undertake a topographical and cell-type specific analysis of ERK
      phosphorylation and two of its downstream targets histone H3 and ribosomal
      protein S6 (rS6) in the dorsal striatum following injection of SKF81297 (D1R-like
      agonist), quinpirole (D2R-like agonist) or apomorphine (non selective DA receptor
      agonist). In striatal areas receiving inputs from the cingulate/prelimbic, visual
      and auditory cortex, SKF81297 treatment increased phosphorylation of ERK, histone
      H3 and rS6 selectively in EGFP-negative MSNs of Drd2-EGFP mice. In contrast, no
      regulation was found in striatal region predominantly targeted by the
      sensorimotor and motor cortex. Apomorphine slightly enhanced ERK and rS6, but not
      histone H3 phosphorylation. This regulation occurred exclusively in EGFP-negative
      neurons mostly in striatal sectors receiving connections from the insular, visual
      and auditory cortex. Quinpirole administration inhibited basal ERK activation but
      did not change histone H3 and rS6 phosphorylation throughout the rostrocaudal
      axis of the dorsal striatum. This anatomo-functional study indicates that D1R and
      D2R agonists produce a unique topography and cell-type specific regulation of the
      ERK cascade signaling in the mouse striatum, and that those patterns are closely
      associated with particular cortical and thalamic inputs. This work evidences the
      need of a precise identification of the striatal areas under study to further
      understand striatal plasticity.

PMID- 22453354
TI  - Kurt Schaffner: from organic photochemistry to photobiology.
AB  - Kurt Schaffner turned 80 this year. This perspective highlights his contributions
      to the research on the plant photoreceptor phytochrome, as many of the findings
      on structure and function of this molecule are tightly linked to the Max-Planck
      Institute for Radiation Chemistry, where he was effective as Max-Planck director
      for more than twenty years.

PMID- 22453356
TI  - The effect of midterm peer feedback on student functioning in problem-based
      tutorials.
AB  - Within Problem-Based Learning successful learning depends on the quality of
      cognitive, social and motivational contributions students make to the tutorial
      group. But at the same time, not all students in PBL automatically contribute in
      a high quality manner, which might impede successful group functioning. This
      study investigated whether peer process feedback combined with goal setting can
      be used to improve the quality of students' individual contributions. A mixed
      methods explanatory design, in which 74 second-year Health Sciences students
      participated, combined a pre- and posttest with a focus group. The results
      indicated that the quality of the contributions only increased for students with
      a below average score on the pre-test. The qualitative data confirmed that the
      impact of the feedback could be increased by combining individual reflection by
      means of goal setting with face-to-face discussion. Another suggestion is to
      investigate whether midterm peer process feedback is more effective for first
      year students, because they are still developing their tutorial behavior, as
      opposed to second year students.

PMID- 22453355
TI  - Expression analysis of mammalian linker-histone subtypes.
AB  - Linker histone H1 binds to the nucleosome core particle and linker DNA,
      facilitating folding of chromatin into higher order structure. H1 is essential
      for mammalian development and regulates specific gene expression in vivo. Among
      the highly conserved histone proteins, the family of H1 linker histones is the
      most heterogeneous group. There are 11 H1 subtypes in mammals that are
      differentially regulated during development and in different cell types. These H1
      subtypes include 5 somatic H1s (H1a-e), the replacement H1(0), 4 germ cell
      specific H1 subtypes, and H1x. The presence of multiple H1 subtypes that differ
      in DNA binding affinity and chromatin compaction ability provides an additional
      level of modulation of chromatin function. Thus, quantitative expression analysis
      of individual H1 subtypes, both of mRNA and proteins, is necessary for better
      understanding of the regulation of higher order chromatin structure and function.
      Here we describe a set of assays designed for analyzing the expression levels of
      individual H1 subtypes. mRNA expression of various H1 variant genes is measured
      by a set of highly sensitive and quantitative reverse transcription-PCR (qRT-PCR)
      assays, which are faster, more accurate and require much less samples compared
      with the alternative approach of Northern blot analysis. Unlike most other
      cellular mRNA messages, mRNAs for most histone genes, including the majority of
      H1 genes, lack a long polyA tail, but contain a stem-loop structure at the 3'
      untranslated region (UTR). Therefore, cDNAs are prepared from total RNA by
      reverse transcription using random primers instead of oligo-dT primers. Realtime
      PCR assays with primers specific to each H1 subtypes are performed to obtain
      highly quantitative measurement of mRNA levels of individual H1 subtypes.
      Expression of housekeeping genes are analyzed as controls for normalization. The
      relative abundance of proteins of each H1 subtype and core histones is obtained
      through reverse phase high-performance liquid chromatography (RP-HPLC) analysis
      of total histones extracted from mammalian cells. The HPLC method and elution
      conditions described here give optimum separations of mouse H1 subtypes. By
      quantifying the HPLC profile, we calculate the relative proportion of individual
      H1 subtypes within H1 family, as well as determine the H1 to nucleosome ratio in
      the cells.

PMID- 22453357
TI  - Dealing with conflicts on knowledge in tutorial groups.
AB  - The aim of our study was to gain understanding of different types of conflicts on
      knowledge in the discussions of problem-based learning tutorial groups, and how
      such conflicts are dealt with. We examined first-year medical and dental
      students' (N = 33) conflicts on knowledge in four videotaped reporting phase
      tutorials. A coding scheme was created for analysing verbatim transcripts of 43
      conflict episodes in order to find out whether the conflict episodes were about
      factual or conceptual knowledge and how the students elaborated the knowledge.
      Conflict episodes were relatively rare (taking up 7.6 % of the time) in the
      videotaped groups. Conflict episodes were more frequently about factual knowledge
      (58 %) than conceptual knowledge (42 %), but conflicts on conceptual knowledge
      lasted longer and were more often elaborated. Elaboration was, however, more
      frequently done individually than collaboratively. Conflict episodes were
      generally fairly short (mean duration 28 s). This was due to a lack of thorough
      argumentation and collaborative elaboration of conflicting ideas. The results
      suggest that students' skills to bring out differences in each other's conceptual
      thinking, the depth of argumentation and the use of questions that elicit
      elaboration need to be improved. Tutors' skills to facilitate the collaborative
      resolving of conflicts on knowledge call for further study.

PMID- 22453358
TI  - Health workforce development: a needs assessment study in French speaking African
      countries.
AB  - In 2006, WHO alerted the world to a global health workforce crisis, demonstrated
      through critical shortages of health workers, primarily in Sub-Saharan Africa
      (WHO in World Health Report, 2006). The objective of our study was to assess, in
      a participative way, the educational needs for public health and health workforce
      development among potential trainees and training institutions in nine French
      speaking African countries. A needs assessment was conducted in the target
      countries according to four approaches: (1) Review at national level of health
      challenges. (2) Semi-directed interviews with heads of relevant training
      institutions. (3) Focus group discussions with key-informants. (4) A
      questionnaire-based study targeting health professionals identified as potential
      trainees. A needs assessment showed important public health challenges in the
      field of health workforce development among the target countries (e.g. unequal
      HRH distribution in the country, ageing of HRH, lack of adequate training). It
      also showed a demand for education and training institutions that are able to
      offer a training programme in health workforce development, and identified
      training objectives and core competencies useful to potential employers and
      future trainees (e.g. leadership, planning/evaluation, management, research
      skill). In combining various approaches our study was able to show a general
      demand for health managers who are able to plan, develop and manage a nation's
      health workforce. It also identified specific competencies that should be
      developed through an education and training program in public health with a focus
      on health workforce development.

PMID- 22453359
TI  - Organocatalytic asymmetric transformations of modified Morita-Baylis-Hillman
      adducts.
AB  - Chiral Lewis basic tertiary amines or phosphines can enable properly modified
      Morita-Baylis-Hillman (MBH) adducts to undergo asymmetric allylic substitutions
      with a wide range of nucleophiles. In addition, assisted by a Bronsted base,
      chiral Lewis bases can also catalytically convert modified MBH adducts into
      allylic ylides, which can be engaged in a variety of asymmetric annulation
      reactions. This tutorial review will focus on such chiral Lewis base-catalysed
      asymmetric transformations of MBH adducts, especially those developed over the
      past five years, allowing for the rapid construction of densely functionalised
      chiral molecules with high levels of regio- and stereoselectivities.

PMID- 22453360
TI  - Incidence of venous thromboembolism in pelvic and acetabular fractures in the
      Japanese population.
AB  - BACKGROUND: There are no detailed reports of the incidence of venous
      thromboembolism (VTE) in pelvic and acetabular fractures in the Asian population.
      The purpose of this study was to investigate the incidence of VTE in pelvic and
      acetabular fractures in the Japanese population. METHODS: Forty-six Japanese
      patients with pelvic and acetabular fractures treated at our hospital from
      February 2004 to April 2011 were analyzed retrospectively. Until April 2009, VTE
      screening was performed by contrast-enhanced computed tomography (CT) or
      ultrasonography (US) when the D-dimer value did not decline predictably, still
      exceeded 20 ug/ml at 5 days after trauma and surgery, or increased >20 ug/ml
      after a period of decline. After April 2009, contrast-enhanced CT and US were
      performed routinely irrespective of the D-dimer value. Physical prophylaxis was
      performed in all patients. The effects of the presence of pelvic and acetabular
      fractures, fracture types, accompanying injuries, and screening strategies on the
      incidences of VTE and pulmonary thromboembolism (PTE) were investigated. RESULTS:
      Overall, 19 patients (41.3%) were diagnosed with VTE and PTE in ten (21.7%). All
      were asymptomatic. Compared with trauma patients without pelvic and acetabular
      fractures treated during the same period, significantly higher incidences of VTE
      and PTE were observed in patients with pelvic and acetabular fractures. No
      significant differences were observed in the incidences of VTE and PTE between
      pelvic and acetabular fractures or between patients with and without accompanying
      injuries. Compared with the previous screening strategy, the detection rates of
      VTE and PTE were higher for the newer screening strategy; however, the difference
      did not reach statistical significance. CONCLUSIONS: We should be vigilant for
      the high incidence of VTE, especially PTE, in patients with pelvic and acetabular
      fractures in the Japanese population.

PMID- 22453362
TI  - Temperature dependence of the frequency noise in a mid-IR DFB quantum cascade
      laser from cryogenic to room temperature.
AB  - We report on the measurement of the frequency noise power spectral density in a
      distributed feedback quantum cascade laser over a wide temperature range, from
      128 K to 303 K. As a function of the device temperature, we show that the
      frequency noise behavior is characterized by two different regimes separated by a
      steep transition at ~200 K. While the frequency noise is nearly unchanged above
      200 K, it drastically increases at lower temperature with an exponential
      dependence. We also show that this increase is entirely induced by current noise
      intrinsic to the device. In contrast to earlier publications, a single laser is
      used here in a wide temperature range allowing the direct assessment of the
      temperature dependence of the frequency noise.

PMID- 22453361
TI  - A novel combination of methotrexate and epigallocatechin attenuates the
      overexpression of pro-inflammatory cartilage cytokines and modulates antioxidant
      status in adjuvant arthritic rats.
AB  - The present study was designed to evaluate the combinatory effect of methotrexate
      (MTX) and epigallocatechin (EGCG) on the progression of adjuvant-induced
      arthritis in rats. Adjuvant arthritis (AA) was induced by a single intradermal
      injection of Freund's complete adjuvant. AA rats were treated with methotrexate
      (0.3 mg/kg) thrice a week, EGCG (100 mg/kg) daily, and combination of MTX and
      EGCG thrice a week for a period of 28 days. Paw swelling changes and
      histopathological and radiographic analysis was assessed to evaluate the
      antiarthritic effect. Lipid peroxidation and antioxidant enzyme activities in
      joint tissue homogenate were performed to observe the modulation of antioxidant
      status along the expression of different pro-inflammatory cartilage cytokines
      like TNF-alpha and IL-6. MTX and EGCG combination potentiated both the
      antiarthritic (decrease of hind paw volume) and the antioxidant effect (SOD, GSH,
      and catalase) as well as suppression of lipid peroxidation. Combination therapy
      of MTX and EGCG significantly inhibited the development phase of arthritis, which
      is supported by histopathological, radiographical, and attenuation of
      overexpression of cartilage cytokines. EGCG act as potent antioxidant and
      immunomodulator, suggesting that combined administration of MTX along with EGCG
      suppressed the development phase of arthritic progression in rats.

PMID- 22453363
TI  - Optimization of a DPP-BOTDA sensor with 25 cm spatial resolution over 60 km
      standard single-mode fiber using Simplex codes and optical pre-amplification.
AB  - Sub-meter distributed optical fiber sensing based on Brillouin optical time
      domain analysis with differential pulse-width pairs (DPP-BOTDA) is combined with
      the use of optical pre-amplification and pulse coding. In order to provide
      significant measurement SNR enhancement and to avoid distortions in the Brillouin
      gain spectrum due to acoustic-wave pre-excitation, the pulse width and duty cycle
      of Simplex coding based on return-to-zero pulses are optimized through
      simulations. In addition, the use of linear optical pre-amplification increases
      the receiver sensitivity and the overall dynamic range of DPP-BOTDA measurements.
      Experimental results demonstrate for first time a spatial resolution of ~25 cm
      over a 60 km standard single-mode fiber (equivalent to ~240 k discrete sensing
      points) with temperature resolution of 1.2 degrees C and strain resolution of 24
      MUepsilon.

PMID- 22453364
TI  - Optically generated reconfigurable photonic structures of elastic quasiparticles
      in frustrated cholesteric liquid crystals.
AB  - We describe laser-induced two-dimensional periodic photonic structures formed by
      localized particle-like excitations in an untwisted confined cholesteric liquid
      crystal. The individual particle-like excitations (dubbed "Torons") contain three
      dimensional twist of the liquid crystal director matched to the uniform
      background director field by topological point defects. Using both single-beam
      steering and holographic pattern generation approaches, the periodic crystal
      lattices are tailored by tuning their periodicity, reorienting their
      crystallographic axes, and introducing defects. Moreover, these lattices can be
      dynamically reconfigurable: generated, modified, erased and then recreated,
      depending on the needs of a particular photonic application. This robust control
      is performed by tightly focused laser beams of power 10-100 mW and by low
      frequency electric fields at voltages ~10 V applied to the transparent
      electrodes.

PMID- 22453365
TI  - Simultaneous frequency conversion, regeneration and reshaping of optical signals.
AB  - Nondegenerate four-wave mixing in fibers enables the tunable and low-noise
      frequency conversion of optical signals. This paper shows that four-wave mixing
      driven by pulsed pumps can also regenerate and reshape optical signal pulses
      arbitrarily.

PMID- 22453366
TI  - Two-dimensional modeling of transient gain gratings in saturable gain media.
AB  - A transient two-dimensional model describing degenerate four-wave mixing inside
      saturable gain media is presented. The new model is compared to existing one
      dimensional models with their qualitative results confirmed. Large quantitative
      differences with respect to peak reflectivity and optimum pump fluence are
      observed. Furthermore, the influence of the beam focus size, the transverse
      position and the crossing angle on the reflectivity of the grating is
      investigated using the improved model. It is demonstrated that the phase
      conjugate reflectivity depends sensitively on the transverse features of the
      interacting beams with a transverse shift in the position of the pump beams
      yielding a threefold improvement in reflectivity.

PMID- 22453367
TI  - Multiple-hologram recording with one-beam encoding.
AB  - This research proposes a method that uses a single object beam to record multiple
      images in a photorefractive crystal medium without having to use any reference
      wave. The object beam in this study is modulated using a lenticular lens array
      sheet to produce a set of sub-object beams. These beams are then angularly
      separated on the recording plane and their scattered waves overlapped in an iron
      doped photorefractive LiNbO3 crystal. This single-exposure, multiple-holographic
      recording method is simple and proven successful via the experiments that
      recorded four holograms in a 30 x 1 mm3 LiNbO3:Fe crystal with single exposure.

PMID- 22453368
TI  - Differentiating surface and bulk interactions using localized surface plasmon
      resonances of gold nanorods.
AB  - We demonstrate a novel localized surface-plasmon resonance sensor that can
      distinguish surface binding interactions from interfering bulk effects. This is
      accomplished by utilizing the longitudinal and transverse plasmon modes of gold
      nanorods. We have investigated, both numerically and experimentally, the effect
      of change in background refractive index and surface binding on the two
      resonances of a gold nanorod on an indium tin oxide coated glass substrate.

PMID- 22453369
TI  - Experimental realization of a four-photon seven-qubit graph state for one-way
      quantum computation.
AB  - We propose and demonstrate the scaling up of photonic graph states through path
      qubit fusion. Two path qubits from separate two-photon four-qubit states are
      fused to generate a two-dimensional seven-qubit graph state composed of
      polarization and path qubits. Genuine seven-qubit entanglement is verified by
      evaluating the witness operator. Six qubits from the graph state are used to
      demonstrate the Deutsch-Jozsa algorithm for general two-bit functions with a
      success probability greater than 90%.

PMID- 22453370
TI  - Reflective three-dimensional displays using the cholesteric liquid crystal with
      an inner patterned retarder.
AB  - We propose a reflective three-dimensional (3D) display using a cholesteric liquid
      crystal (ChLC) with an inner patterned retarder producing half-wave retardation.
      The inner patterned retarder, fabricated by selective ultra-violet exposure to
      the aligned reactive mesogen, divides the circularly polarized light reflected
      from the ChLC layer into two orthogonal circular polarizations. These reflected
      orthogonal polarizations construct stereoscopic 3D images without any optical
      components such as a polarizer and backlight unit.

PMID- 22453371
TI  - Depth-dependent cerebral hemodynamic responses following direct cortical
      electrical stimulation (DCES) revealed by in vivo dual-optical imaging
      techniques.
AB  - We studied depth-dependent cerebral hemodynamic responses of rat brain following
      direct cortical electrical stimulation (DCES) in vivo with optical recording of
      intrinsic signal (ORIS) and near-infrared spectroscopy (NIRS). ORIS is used to
      visualize the immediate hemodynamic changes in cortical areas following the
      stimulation, whereas NIRS measures the hemodynamic changes originating from
      subcortical areas. We found strong hemodynamic changes in relation to DCES both
      in ORIS and NIRS data. In particular, the signals originating from cortical areas
      exhibited a tri-phasic response, whereas those originating from subcortical
      regions exhibited multi-phasic responses. In addition, NIRS signals from two
      different sets of source-detector separation were compared and analyzed to
      investigate the causality of perfusion, which demonstrated downstream
      propagation, indicating that the upper brain region reacted faster than the deep
      region.

PMID- 22453372
TI  - Thermal and laser properties of Nd:Lu3Sc1.5Ga3.5O12 for high power dual
      wavelength laser.
AB  - We measured the thermal properties of Nd:Lu3Sc1.5Ga3.5O12 (Nd:LuSGG) crystal,
      including the thermal expansion coefficient, specific heat, and thermal diffusion
      coefficient. The calculated thermal conductivity is 4.4 W/mK at room temperature.
      A high-power continuous-wave and passively Q-switched Nd:LuSGG laser was also
      demonstrated. Continuous-wave output power of 6.96 W is obtained which is the
      highest power with this material. For the first time to our knowledge, the
      passively Q-switched Nd:LuSGG laser is reported with the shortest pulse width,
      largest pulse energy, and highest peak power are achieved to be 5.1 ns, 62.5 MUJ,
      and 12 kW, respectively. By spectral analysis, it has been found that the
      Nd:LuSGG laser was located at 1059 nm under low pump power, and became dual
      wavelength at 1061.5 and 1059 nm when the incident pump power is over 2.27 W. The
      generating mechanism of dual-wavelength laser is also discussed.

PMID- 22453373
TI  - Inducing transparency with large magnetic response and group indices by hybrid
      dielectric metamaterials.
AB  - We present metamaterial-induced transparency (MIT) phenomena with enhanced
      magnetic fields in hybrid dielectric metamaterials. Using two hybrid structures
      of identical-dielectric-constant resonators (IDRs) and distinct-dielectric
      constant resonators (DDRs), we demonstrate a larger group index (ng~354), better
      bandwidth-delay product (BDP~0.9) than metallic-type metamaterials. The keys to
      enable these properties are to excite either the trapped mode or the suppressed
      mode resonances, which can be managed by controlling the contrast of dielectric
      constants between the dielectric resonators in the hybrid metamaterials.

PMID- 22453374
TI  - Multi-octave tunable RF signal generation based on a dual-polarization fiber
      grating laser.
AB  - A simple technique has been proposed and demonstrated to generate radio-frequency
      (RF) signal based on a fiber grating laser with multi-octave tunablity. The laser
      is fabricated by inscribing a wavelength-matched Bragg grating pair in a short
      section of low-birefringence Er/Yb co-doped fiber. A RF signal can be obtained by
      beating the two-polarization mode output with its frequency determined by the
      birefringence within the cavity. By slicing the laser cavity into two sections
      and then aligning them with a rotated angle, the output beat frequency can be
      continuously tuned in a multi-octave frequency range as shown in the experiment
      from 2.05 GHz down to 289 MHz, as a result of the induced change in optical
      length for each polarization mode. The present technique has the advantages
      including simple scheme and large tuning range, and the ability of tuning could
      be further improved by use of active fibers with higher birefringence.

PMID- 22453375
TI  - Resonant optical excitations in complementary plasmonic nanostructures.
AB  - We compare the plasmonic response of two complementary structures to a scanning
      electron probe; a silver nanowire and a nanoslot in a silver film of comparable
      dimensions, desirable for their localized electromagnetic enhancement and
      enhanced optical transmission respectively. Through electron energy loss
      spectroscopy, multiple plasmonic resonant harmonics setup in both structures are
      resolved with inverted phase, in agreement with Babinet's principle, and of
      consequence in the design and fabrication of nanostructures.

PMID- 22453376
TI  - Fast visible light photoelectric switch based on ultralong single crystalline
      V2O5 nanobelt.
AB  - A photoelectric switch with fast response to visible light (<200 MUs), suitable
      photosensitivity and excellent repeatability is proposed based on the ultralong
      single crystalline V2O5 nanobelt, which are synthesized by chemical vapor
      deposition and its photoconductive mechanism can well be explained by small
      polaron hopping theory. Our results reveal that the switch has a great potential
      in next generation photodetectors and light-wave communications.

PMID- 22453377
TI  - An ellipse model for cavity mode behavior of optically injection-locked VCSELs.
AB  - We report a new graphical tool to analyze optical injection-locked vertical
      cavity surface-emitting lasers (VCSELs). It predicts the resonant frequency
      enhancement and cavity mode behavior for both single- and multi- mode VCSELs
      under injection locking. Calculations based on this model show excellent
      agreement with experimental results.

PMID- 22453378
TI  - The development and application of femtosecond laser systems.
AB  - Some background as well as recent progress in the development of femtosecond
      lasers are discussed together with a brief outline of a few representative
      emergent applications in biology and medicine that are underpinned by access to
      such sources. We also provide a short summary of other contributions in this
      focus issue.

PMID- 22453379
TI  - High power laser pulses with voltage controlled durations of 400 - 1000 ps.
AB  - We report on the generation and amplification of pulses with pulse widths of 400 
      1000 ps at 1064 nm. For pulse generation an ultra-fast semiconductor modulator
      is used that modulates a cw-beam of a DFB diode laser. The pulse lengths could be
      adjusted by the use of a voltage control. The pulses were amplified in a solid
      state Nd:YVO4 regenerative amplifier to an average power of up to 47.7 W at 100 -
      816 kHz.

PMID- 22453380
TI  - High-power, high repetition-rate, green-pumped, picosecond LBO optical parametric
      oscillator.
AB  - We report on a picosecond, green-pumped, lithium triborate optical parametric
      oscillator with record-high output power. It was synchronously pumped by a
      frequency-doubled (530 nm), pulse-compressed (4.4 ps), high-repetition-rate (230
      MHz), fiber-amplified gain-switched laser diode. For a pump power of 17 W, a
      maximum signal and idler power of 3.7 W and 1.8 W was obtained from the optical
      parametric oscillator. A signal pulse duration of ~3.2 ps was measured and wide
      tunability from 651 nm to 1040 nm for the signal and from 1081 nm to 2851 nm for
      the idler was achieved.

PMID- 22453381
TI  - Multi-microjoule, MHz repetition rate Ti:sapphire ultrafast regenerative
      amplifier system.
AB  - We demonstrate a cryogenically cooled Ti:sapphire ultrafast regenerative
      amplifier laser system producing >20 MUJ energies at 50 kHz, >12 MUJ at 200 kHz
      and >3.5 MUJ at 1MHz with repetition rates continuously tunable from 50 kHz up to
      1.7 MHz in a footprint of only 60x180 cm2. This laser uses down-chirped pulse
      amplification employing a grism stretcher and a glass-block compressor, achieving
      sub-60-fs pulse duration. This laser represents a several-times improvement in
      repetition-rate and average power over past Ti:sapphire-based ultrafast lasers in
      this class. We discuss the unique challenges and solutions for this laser system.
      This laser system has wide applications especially in ultrafast photoemission,
      nonlinear imaging and spectroscopy, as well as for micro/nano-machining and
      ultrafast laser therapy and surgery.

PMID- 22453382
TI  - Algorithm-based continuous pulse duration tuning and performance control of a
      mode-locked laser diode.
AB  - A control algorithm is presented that addresses the stability issues inherent to
      the operation of monolithic mode-locked laser diodes. It enables a continuous
      pulse duration tuning without any onset of Q-switching instabilities. A
      demonstration of the algorithm performance is presented for two radically
      different laser diode geometries and continuous pulse duration tuning between 0.5
      ps to 2.2 ps and 1.2 ps to 10.2 ps is achieved. With practical applications in
      mind, this algorithm also facilitates control over performance parameters such as
      output power and wavelength during pulse duration tuning. The developed algorithm
      enables the user to harness the operational flexibility from such a laser with
      'push-button' simplicity.

PMID- 22453383
TI  - Ultrashort superradiant pulse generation from a GaN/InGaN heterostructure.
AB  - Dicke superradiance from a two-section violet GaN/InGaN semiconductor laser diode
      is demonstrated for the first time. In the superradiance regime, optical pulses
      with peak powers in excess of 2.8 W and durations as short as 1.4 ps are
      generated at repetition rates of up to 10 MHz at the emission wavelength of 408
      nm. The properties of superradiant pulse generation from these GaN/InGaN laser
      diodes are very similar to those reported for infrared AlGaAs/GaAs laser diodes.

PMID- 22453384
TI  - 175 GHz, 400-fs-pulse harmonically mode-locked surface emitting semiconductor
      laser.
AB  - We report a harmonically mode-locked vertical external cavity surface emitting
      laser (VECSEL) producing 400 fs pulses at a repetition frequency of 175 GHz with
      an average output power of 300 mW. Harmonic mode-locking was established using a
      300 um thick intracavity single crystal diamond heat spreader in thermal contact
      with the front surface of the gain sample using liquid capillary bonding. The
      repetition frequency was set by the diamond microcavity and stable harmonic mode
      locking was achieved when the laser cavity length was tuned so that the laser
      operated on the 117th harmonic of the fundamental cavity. When an etalon placed
      intracavity next to the gain sample, but not in thermal contact was used pulse
      groups were observed. These contained 300 fs pulses with a spacing of 5.9 ps. We
      conclude that to achieve stable harmonic mode locking at repetition frequencies
      in the 100s of GHz range in a VECSEL there is a threshold pulse energy above
      which harmonic mode locking is achieved and below which groups of pulses are
      observed.

PMID- 22453385
TI  - Octave-spanning ultrafast OPO with 2.6-6.1 um instantaneous bandwidth pumped by
      femtosecond Tm-fiber laser.
AB  - We report the extension of broadband degenerate OPO operation further into mid
      infrared. A femtosecond thulium fiber laser with output centered at 2050 nm
      synchronously pumps a 500-MUm-long crystal of orientation patterned GaAs
      providing broadband gain centered at 4.1 um. We observe a pump threshold of 17 mW
      and output bandwidth extending from 2.6 to 6.1 um at the -30 dB level. Average
      output power was 37 mW. Appropriate resonator group dispersion is a key factor
      for achieving degenerate operation with instantaneously broad bandwidth. The
      output spectrum is very sensitive to absorption and dispersion introduced by
      molecular species inside the OPO cavity.

PMID- 22453386
TI  - Frontiers in passively mode-locked high-power thin disk laser oscillators.
AB  - Semiconductor saturable absorber mirror (SESAM) mode-locked thin disk lasers
      define the state-of-the-art performance for high average power and high pulse
      energy femtosecond laser oscillators. To date pulse energies above 30 uJ and
      average powers above 140 W have been demonstrated. In this paper we review the
      achievements of mode-locked thin disk lasers in terms of average power and pulse
      energy. Stable mode locking requires single transverse mode operation even at the
      highest average power, which is challenging and therefore addressed in more
      detail. We then summarize our expectations on the main challenges and
      limitiations for the next generation of mode-locked thin disk laser oscillators
      with an average power above 500 W and pulse energies in excess of 100 uJ.

PMID- 22453387
TI  - Optical trapping with "on-demand" two-photon luminescence using Cr:LiSAF laser
      with optically addressed saturable Bragg reflector.
AB  - We demonstrate a diode-pumped Cr:LiSAF laser with controllable and reliable fast
      switching between its continuous-wave and mode-locked states of operation using
      an optically-addressed semiconductor Bragg reflector, permitting dyed
      microspheres to be continuously trapped and monitored using a standard microscope
      imaging and on-demand two-photon-excited luminescence techniques.

PMID- 22453388
TI  - Efficient light amplification in low gain materials due to a photonic band edge
      effect.
AB  - One of the possibilities of increasing optical gain of a light emitting source is
      by embedding it into a photonic crystal (PhC). If the properties of the PhC are
      tuned so that the emission wavelength of the light source with gain falls close
      to the photonic band edge of the PhC, then due to low group velocity of the light
      modes near the band edge caused by many multiple reflections of light on the
      photonic structure, the stimulated emission can be significantly enhanced. Here,
      we perform simulation of the photonic band edge effect on the light intensity of
      spectrally broad source interacting with a diamond PhC with low optical gain. We
      show that even for the case of low gain, up to 10-fold increase of light
      intensity output can be obtained for the two-dimensional PhC consisting of only
      19 periodic layers of infinitely high diamond rods ordered into a square lattice.
      Moreover, considering the experimentally feasible structure composed of diamond
      rods of finite height - PhC slab - we show that the gain enhancement, even if
      reduced compared to the ideal case of infinite rods, still remains relatively
      high. For this particular structure, we show that up to 3.5-fold enhancement of
      light intensity can be achieved.

PMID- 22453389
TI  - Ultra-low-power carrier-depletion Mach-Zehnder silicon optical modulator.
AB  - We demonstrate a 26 Gbit/s Mach-Zehnder silicon optical modulator. The doping
      concentration and profile are optimized, and a modulation efficiency with the
      figure of merit (VpiL) of 1.28 V.cm is achieved. We design an 80-nm-wide
      intrinsic silicon gap between the p-type and n-type doped regions to reduce the
      capacitance of the diode and prevent the diode from working in a slow diffusion
      mode. Therefore, the modulator can be driven with a small differential voltage of
      0.5 V with no bias. Without the elimination of the dissipated power of the series
      resistors and the reflected power of the electrical signal, the maximum power
      consumption is 3.8 mW.

PMID- 22453390
TI  - Multiwavelength erbium-doped fiber laser based on a nonlinear amplifying loop
      mirror assisted by un-pumped EDF.
AB  - A multiwavelength erbium-doped fiber (EDF) laser based on a nonlinear amplifying
      loop mirror (NALM) is proposed and experimentally demonstrated. The NALM provides
      intensity-dependent transmissivity to equalize different-wavelength powers and
      the transmission can be uniquely optimized by controlling the cavity loss
      associated with a section of un-pumped EDF, which also enhances the output signal
      to-noise ratio (SNR). Through adjusting the polarization controllers (PCs), under
      only 70 mW pump power, up to 62-wavelength output with channel spacing of 0.45 nm
      has been achieved. Also, the lasing tunability and stability are verified.

PMID- 22453391
TI  - Co-sputtered SiC + Ag nanomixtures as visible wavelength negative index
      metamaterials.
AB  - The fabrication and characterization of a novel metamaterial that shows negative
      index in the visible (blue) is reported. The real part of the negative index of
      this metamaterial at 405 nm, comprising co-sputtered SiC + Ag nanoparticle
      mixture on a glass substrate, is deduced from results of double Michelson
      interferometry setup which shows a negative phase delay. It is numerically
      verified that this metamaterial can yield near-field super-resolution imaging for
      both TE and TM polarizations.

PMID- 22453392
TI  - Bandwidth enhancement of waveguide-coupled photodetectors with inductive gain
      peaking.
AB  - Silicon has recently attracted a great deal of interest as an economical platform
      for integrated photonics systems. Integrated photodetectors are a key component
      of such systems, and CMOS-compatible processes involving epitaxially grown
      germanium for photodetection have been demonstrated. Detector parasitic
      capacitance is a key limitation, which will likely worsen if techniques such as
      bump bonding are employed. Here we propose leveraging the complexity available in
      silicon photonics processes to compensate for this using a technique known as
      gain peaking. We predict that by simply including an inductor and capacitor in
      the photodetector circuit with the properly chosen values, detector bandwidths
      can be as much as doubled, with no undesired effects.

PMID- 22453393
TI  - Spheroidal Fabry-Perot microcavities in optical fibers for high-sensitivity
      sensing.
AB  - All-optical-fiber Fabry-Perot interferometers (FPIs) with microcavities of
      different shapes were investigated. It was found that the size and shape of the
      cavity plays an important role on the performance of these interferometers. To
      corroborate the analysis, FPIs with spheroidal cavities were fabricated by
      splicing a photonic crystal fiber (PCF) with large voids and a conventional
      single mode fiber (SMF), using an ad hoc splicing program. It was found that the
      strain sensitivity of FPIs with spheroidal cavities can be controlled through the
      dimensions of the spheroid. For example, a FPI whose cavity had a size of ~10x60
      MUm exhibited strain sensitivity of ~10.3 pm/MUepsilon and fringe contrast of ~38
      dB. Such strain sensitivity is ~10 times larger than that of the popular fiber
      Bragg gratings (~1.2 pm/MUepsilon) and higher than that of most low-finesse FPIs.
      The thermal sensitivity of our FPIs is extremely low (~1pm/ degrees C) due to the
      air cavities. Thus, a number of temperature-independent ultra-sensitive
      microscopic sensors can be devised with the interferometers here proposed since
      many parameters can be converted to strain. To this end, simple vibration sensors
      are demonstrated.

PMID- 22453394
TI  - Full waveform hyperspectral LiDAR for terrestrial laser scanning.
AB  - We present the design of a full waveform hyperspectral light detection and
      ranging (LiDAR) and the first demonstrations of its applications in remote
      sensing. The novel instrument produces a 3D point cloud with spectral
      backscattered reflectance data. This concept has a significant impact on remote
      sensing and other fields where target 3D detection and identification is crucial,
      such as civil engineering, cultural heritage, material processing, or
      geomorphological studies. As both the geometry and spectral information on the
      target are available from a single measurement, this technology will extend the
      scope of imaging spectroscopy into spectral 3D sensing. To demonstrate the
      potential of the instrument in the remote sensing of vegetation, 3D point clouds
      with backscattered reflectance and spectral indices are presented for a specimen
      of Norway spruce.

PMID- 22453395
TI  - Generation of high-order Hermite-Gaussian modes in end-pumped solid-state lasers
      for square vortex array laser beam generation.
AB  - This study reports the first systematic approach to the excitation of all high
      order Hermite-Gaussian modes (HGMs) in end-pumped solid-state lasers. This study
      uses a metal-wire-inserted laser resonator accompanied with the "off axis
      pumping" approach. This study presents numerical analysis of the excitation of
      HGMs in end-pumped solid-state lasers and experimentally generated HGM patterns.
      This study also experimentally demonstrates the generation of an square vortex
      array laser beams by passing specific high-order HGMs (HGn,n + 1 or HGn + 1,n
      modes) through a Dove prism-embedded unbalanced Mach-Zehnder interferometer
      [Optics Express 16, 19934-19949]. The resulting square vortex array laser beams
      with embedded vortexes aligned in a square array can be applied to multi-spot
      dark optical traps in the future.

PMID- 22453396
TI  - Free carrier induced spectral shift for GaAs filled metallic hole arrays.
AB  - For a GaAs filled metallic hole array on a pre-epi GaAs substrate, the free
      carriers, generated by three-photon absorption (3PA) assisted by strongly
      enhanced local fields, reduce the refractive index of GaAs in ~200-nm thick
      active area through band filling and free carrier absorption. Therefore, the
      surface plasma wave (SPW) resonance, and the related second harmonic (SH)
      spectrum blue shifts with increasing fluence; For the plasmonic structure on a
      substrate with surface defects, free carrier recombination dominates. The band
      gap emission spectral peak wavelength decreases 10-nm with increasing fluence,
      showing the transition from nonradiative-, at low excitation, to bimolecular
      recombination at high carrier concentrations.

PMID- 22453397
TI  - Dispersion relation for surface plasmon polaritons on a Schottky junction.
AB  - The conventional analysis of surface plasmon modes on dielectric-metal interfaces
      requires clearly defining the permittivity discontinuity at the interface. A
      pivotal assumption of such an analysis is that the formation of the dielectric
      metal interface does not change the material properties and the materials forming
      the interface have identical permittivities before and after the formation of the
      interface. However, this assumption breaks down if an interface is made between a
      metal and a semiconductor which is commonly known as a Schottky junction. Under
      certain conditions, such an interface can sustain a surface plasmon polariton
      (SPP) mode. It is also possible to change the properties of the media surrounding
      the Schottky junction interface by applying an external potential difference
      across the junction. Central to the understanding of the SPP mode behaviour in
      such a complex morphological interface is the dispersion relation which defines
      the feasible SPP modes and their characteristics. Here, we carry out a detailed
      analysis to derive an analytical expression for the dispersion relation for a
      Schottky junction. Our analysis takes into account the space charge layer formed
      due to the charge distribution across the Schottky junction and resulting new
      boundary conditions.

PMID- 22453398
TI  - Interference theory of metamaterial perfect absorbers.
AB  - The impedance matching to free space in metamaterial perfect absorbers has been
      believed to involve and rely on magnetic resonant response, with direct evidence
      provided by the anti-parallel surface currents in the metal structures. Here I
      present a different theoretical interpretation based on interference, which shows
      that the two layers of metal structures in metamaterial absorbers are linked only
      by multiple reflections with negligible near-field interactions or magnetic
      resonances. This is further supported by the out-of-phase surface currents
      derived at the interfaces of resonator array and ground plane through multiple
      reflections and superpositions. The theory developed here explains all features
      observed in narrowband metamaterial absorbers and therefore provides a profound
      understanding of the underlying physics.

PMID- 22453399
TI  - Hybrid-resolution multispectral imaging using color filter array.
AB  - Hybrid-resolution multispectral imaging is a framework to acquire multispectral
      images through a reconstruction procedure using two types of measurement data
      with different spatial and spectral resolutions. In this paper, we propose a new
      method for such a framework on the basis of a full-resolution RGB image and the
      data obtained from an image sensor with a multispectral filter array (MSFA). In
      the proposed method, a small region of each image band is reconstructed as a
      linear combination of RGB images, where the weighting coefficients are determined
      using MSFA data. The effectiveness of the proposed approach is shown by
      simulations using spectral images of natural scenes.

PMID- 22453400
TI  - Crescent shaped dielectric periodic structure for light manipulation.
AB  - We present optical properties of crescent-shaped dielectric nano-rods that
      comprise a square lattice periodic structure named as crescent-shaped photonic
      crystals (CPC). The circular symmetry of individual cells of periodic dielectric
      structures is broken by replacing each unit cell with a reduced symmetry crescent
      shaped structure. The created configuration is assumed to be formed by the
      intersection of circular dielectric and air rods. The degree of freedom to
      manipulate the light propagation arises due to the rotational sensitivity of the
      CPC. The interesting dispersion property of designed CPC occurs due to the
      anisotropic nature of the iso-frequency contours that yield tilted self
      collimated wave guiding. Furthermore, this feature allows focusing, routing,
      splitting and deflecting light beams along certain routes which are independent
      of the lattice symmetry directions of regular PCs. The propagation direction of
      light can be tuned by means of the opening angle of the crescent shape. Finally,
      the property of being all-dielectric structure ensures the absence of optical
      absorption losses that are reminiscent of employed metallic nano-particles.

PMID- 22453401
TI  - All-optical phase modulation for integrated interferometric biosensors.
AB  - We present the theoretical and the experimental implementation of an all-optical
      phase modulation system in integrated Mach-Zehnder Interferometers to solve the
      drawbacks related to the periodic nature of the interferometric signal. Sensor
      phase is tuned by modulating the emission wavelength of low-cost commercial laser
      diodes by changing their output power. FFT deconvolution of the signal allows for
      direct phase readout, immune to sensitivity variations and to light intensity
      fluctuations. This simple phase modulation scheme increases the signal-to-noise
      ratio of the measurements in one order of magnitude, rendering in a sensor with a
      detection limit of 1.9.10-7 RIU. The viability of the all-optical modulation
      approach is demonstrated with an immunoassay detection as a biosensing proof of
      concept.

PMID- 22453402
TI  - Transparency window for the absorptive dipole resonance in a symmetry-reduced
      grating structure.
AB  - We demonstrate that a transparency window can be obtained within the absorptive
      dipole resonant regime, by slightly reducing the symmetric arrangement of a
      dipole-like bar grating covered by a waveguiding layer. The physical
      understanding is that, under the condition of reducing the grating symmetry, the
      lossy dipole plasmon resonance can be completely transferred into the waveguide
      mode in a way of destructive interference. In accompany with the tunable
      transparency window modulated by the symmetry-reduced displacement, an ultra high
      group index (slowing down the light) as well as a vortex distribution of the
      electromagnetic field is found.

PMID- 22453403
TI  - On the origin of near-IR luminescence in Bi-doped materials (II). Subvalent
      monocation Bi+ and cluster Bi53+ luminescence in AlCl3/ZnCl2/BiCl3 chloride
      glass.
AB  - Broadband NIR photoluminescence (from 1000 to 2500 nm) was observed from
      partially reduced AlCl3/ZnCl2/BiCl3 glass, containing subvalent bismuth species.
      The luminescence consists of three bands, assigned to Bi+ , Bi24+, and Bi53+
      ions. The physical and optical characteristics of these centers and possible
      contribution to NIR luminescence from bismuth-doped oxide glasses are discussed.

PMID- 22453404
TI  - Objective-first design of high-efficiency, small-footprint couplers between
      arbitrary nanophotonic waveguide modes.
AB  - We present an algorithm for designing high efficiency (~98%), small-footprint
      (1.5-4 square vacuum wavelengths) couplers between arbitrary nanophotonic
      waveguide modes in two dimensions. Our "objective-first" method is
      computationally fast (15 minutes on a single-core personal computer), requires no
      trial-and-error, and does not require guessing a good starting design. We
      demonstrate designs for various coupling problems which suggest that our method
      allows for the design of any single-mode, linear optical device.

PMID- 22453405
TI  - Short temporal coherence digital holography with a femtosecond frequency comb
      laser for multi-level optical sectioning.
AB  - In this paper, we demonstrate how short temporal coherence digital holography
      with a femtosecond frequency comb laser source may be used for multi-level
      optical sectioning. The object shape is obtained by digitally reconstructing and
      processing a sequence of holograms recorded during stepwise shifting of a mirror
      in the reference arm. Experimental results are presented.

PMID- 22453406
TI  - Low-loss polysilicon waveguides fabricated in an emulated high-volume electronics
      process.
AB  - We measure end-of-line polysilicon waveguide propagation losses of ~6-15 dB/cm
      across the telecommunication O-, E-, S-, C- and L-bands in a process
      representative of high-volume product integration. The lowest loss of 6.2 dB/cm
      is measured at 1550 nm in a polysilicon waveguide with a 120 nm x 350 nm core
      geometry. The reported waveguide characteristics are measured after the thermal
      cycling of the full CMOS electronics process that results in a 32% increase in
      the extracted material loss relative to the as-crystallized waveguide samples.
      The measured loss spectra are fit to an absorption model using defect state
      parameters to identify the dominant loss mechanism in the end-of-line and as
      crystallized polysilicon waveguides.

PMID- 22453407
TI  - Coherence properties of a broadband femtosecond mid-IR optical parametric
      oscillator operating at degeneracy.
AB  - We study coherence properties of a chi(2) optical parametric oscillator (OPO),
      which produces 2/3-octave-wide spectrum centered at the subharmonic (3120 nm) of
      the femtosecond pump laser. Our method consists of interfering the outputs of two
      identical, but independent OPOs pumped by the same laser. We demonstrate that the
      two OPOs show stable spatial and temporal interference and are mutually locked in
      frequency and in phase. By observing a collective heterodyne beat signal between
      the two OPOs we show that one can deterministically choose, by cavity length
      adjustment, between the two frequency states corresponding to the two sets of
      modes shifted with respect to each other by half of the laser pulse repetition
      rate. Moreover, we observe that the existence of two opposite phase states, a
      known common feature of a parametrically driven n = 2 subharmonic oscillator,
      reveals itself in our experiment as a common phase, 0 or pi, being established
      through the whole set of some 300 thousand longitudinal modes.

PMID- 22453408
TI  - Optimizing single mode robustness of the distributed modal filtering rod fiber
      amplifier.
AB  - High-power fiber amplifiers for pulsed applications require large mode area (LMA)
      fibers having high pump absorption and near diffraction limited output. Photonic
      crystal fibers allow realization of short LMA fiber amplifiers having high pump
      absorption through a pump cladding that is decoupled from the outer fiber
      diameter. However, achieving ultra low NA for single mode (SM) guidance is
      challenging, thus different design strategies must be applied. The distributed
      modal filtering (DMF) design enables SM guidance in ultra low NA fibers with very
      large cores, where large preform tolerances can be compensated during the fiber
      draw. Design optimization of the SM bandwidth of the DMF rod fiber is presented.
      Analysis of band gap properties results in a fourfold increase of the SM
      bandwidth compared to previous results, achieved by utilizing the first band of
      cladding modes, which can cover a large fraction of the Yb emission band
      including wavelengths of 1030 nm and 1064 nm. Design parameters tolerating
      refractive index fabrication uncertainties of +/- 10-4 are targeted to yield
      stable SM bandwidths.

PMID- 22453409
TI  - Drift estimation for single marker switching based imaging schemes.
AB  - In recent years, the diffraction barrier in fluorescence imaging has been broken
      and optical nanoscopes now routinely image with resolutions of down to 20 nm, an
      improvement of more than 10 fold. Because this allows imaging much smaller
      features and because all super-resolution approaches trade off speed for spatial
      resolution, mechanical instabilities of the microscopes become a limiting factor.
      Here, we propose a fully data-driven statistical registration method for drift
      detection and drift correction for single marker switching (SMS) imaging schemes,
      including a guideline for parameter choice and quality checks of the drift
      analysis. The necessary assumptions about the drift are minimal, allowing a model
      free approach, but more specific models can easily be integrated. We determine
      the resulting performance on standard SMS measurements and show that the drift
      determination can be routinely brought to the range of precision achievable by
      fiducial marker-tracking methods.

PMID- 22453411
TI  - Study on transition from photonic-crystal laser to random laser.
AB  - The dependence of the lasing threshold on the amount of positional disorder in
      photonic crystal structures is newly studied by means of the finite element
      method, not of the finite difference time domain method usually used. A two
      dimensional model of a photonic crystal consisting of dielectric cylinders
      arranged on a triangular lattice within a circular region is considered. The
      cylinders are assumed to be homogeneous and infinitely long. Positional disorder
      of the cylinders is introduced to the photonic crystals. Optically active medium
      is introduced to the interspace among the cylinders. The population inversion
      density of the optically active medium is modeled by the negative imaginary part
      of dielectric constant. The ratio between radiative power of electromagnetic
      field without amplification and that with amplification is computed as a function
      of the frequency and the imaginary part of the dielectric constant, and the
      threshold of the imaginary part, namely population inversion density for laser
      action is obtained. These analyses are carried out for various amounts of
      disorder. The variation of the lasing threshold from photonic-crystal laser to
      random laser is revealed by systematic computations with numerical method of
      reliable accuracy for the first time. Moreover, a novel phenomenon, that the
      lasing threshold have a minimum against the amount of disorder, is found. In
      order to investigate the properties of the lasing states within the circular
      system, the distributions of the electric field amplitudes of the states are also
      calculated.

PMID- 22453410
TI  - Digistain: a digital staining instrument for histopathology.
AB  - We describe a new mid-infrared (mid-IR) imaging method specifically designed to
      augment the H + E tissue staining protocol. Images are taken with bespoke IR
      filters at wavelengths that enable chemical maps to be generated, corresponding
      to the cytoplasmic (amide) and nuclear (phosphodiester) components of unstained
      oesophageal tissue sections. A suitably calibrated combination of these generates
      false colour computer images that reproduce not only the tissue morphology, but
      also accurate and quantitative distributions of the nuclear-to-cytoplasmic ratio
      throughout the tissue section. This parameter is a well documented marker of
      malignancy, and because the images can be taken and interpreted by clinically
      trained personnel in a few seconds, we believe this new "digistain" approach
      makes spectroscopic mid-IR imaging techniques available for the first time as a
      practical, specific and sensitive augmentation to standard clinical cancer
      diagnosis methods.

PMID- 22453412
TI  - PMD tolerant direct-detection polarization division multiplexed OFDM systems with
      MIMO processing.
AB  - This work proposes a novel direct-detection polarization division multiplexed
      OFDM scheme without the need of dynamic polarization control at a polarization
      diverse receiver, and the proposed scheme is robust against polarization mode
      dispersion. Setting the frequency difference between two polarization-orthogonal
      reference carriers as one subcarrier spacing, possible signal fading can be
      avoided, and the corresponding interference from adjacent subcarriers is
      eliminated by a novel MIMO algorithm. The penalty caused by high channel matrix
      condition number can be decreased by inserting empty tones among subcarriers, and
      the polarization-dependent OSNR penalty at the BER of 10-3 is <3.6 dB with an
      empty tone inserted every 8 subcarriers. Moreover, the numerical results
      demonstrate the 16 * 103-ps/nm chromatic dispersion and the 300-ps differential
      group delay will not induce additional penalty.

PMID- 22453413
TI  - Incorporation of an experimentally determined MTF for spatial frequency filtering
      and deconvolution during optical projection tomography reconstruction.
AB  - We demonstrate two techniques to improve the quality of reconstructed optical
      projection tomography (OPT) images using the modulation transfer function (MTF)
      as a function of defocus experimentally determined from tilted knife-edge
      measurements. The first employs a 2-D binary filter based on the MTF frequency
      cut-off as an additional filter during back-projection reconstruction that
      restricts the high frequency information to the region around the focal plane and
      progressively decreases the spatial frequency bandwidth with defocus. This helps
      to suppress "streak" artifacts in OPT data acquired at reduced angular sampling,
      thereby facilitating faster OPT acquisitions. This method is shown to reduce the
      average background by approximately 72% for an NA of 0.09 and by approximately
      38% for an NA of 0.07 compared to standard filtered back-projection. As a
      biological illustration, a Fli:GFP transgenic zebrafish embryo (3 days post
      fertilisation) was imaged to demonstrate the improved imaging speed (a quarter of
      the acquisition time). The second method uses the MTF to produce an appropriate
      deconvolution filter that can be used to correct for the spatial frequency
      modulation applied by the imaging system.

PMID- 22453414
TI  - Evaluation of sCMOS cameras for detection and localization of single Cy5
      molecules.
AB  - The ability to detect single molecules over the electronic noise requires high
      performance detector systems. Electron Multiplying Charge-Coupled Device (EMCCD)
      cameras have been employed successfully to image single molecules. Recently,
      scientific Complementary Metal Oxide Semiconductor (sCMOS) based cameras have
      been introduced with very low read noise at faster read out rates, smaller pixel
      sizes and a lower price compared to EMCCD cameras. In this study, we have
      compared the two technologies using two EMCCD and three sCMOS cameras to detect
      single Cy5 molecules. Our findings indicate that the sCMOS cameras perform
      similar to EMCCD cameras for detecting and localizing single Cy5 molecules.

PMID- 22453415
TI  - A simple and efficient frequency offset estimation algorithm for high-speed
      coherent optical OFDM systems.
AB  - In this paper, we propose a simple frequency offset estimation (FOE) algorithm
      for high-speed coherent optical orthogonal frequency-division multiplexing (CO
      OFDM) systems, which avoids the exhaustive search computations on the integer
      part of FOE by using a merit function. In time domain, the FOE algorithm can
      estimate all the frequency offset in the range of [-5GHz, +5GHz], for satisfying
      the practical application requirement, based on only one redesigned training
      symbol. In addition, we provide the theoretical analysis about the quantitative
      influences of the residual frequency offset (RFO) on CO-OFDM systems. In order to
      reduce the final estimation error, a new zero-overhead residual frequency offset
      estimation (RFOE) algorithm is also proposed in this paper. Finally, the
      feasibility and effectiveness of the proposed FOE and RFOE algorithms are
      demonstrated in a 464 Gbit/s polarization-division multiplexed (PDM) 16-ary
      quadrature amplitude modulation (QAM) CO-OFDM system by the simulation, and
      numerical results validate the proposed algorithms.

PMID- 22453416
TI  - Strategies to maximize the performance of a STED microscope.
AB  - In stimulated emission depletion (STED) microscopy, the spatial resolution scales
      as the inverse square root of the STED beam's intensity. However, to fully
      exploit the maximum effective resolution achievable for a given STED beam's
      intensity, several experimental precautions have to be considered. We focus our
      attention on the temporal alignment between the excitation and STED pulses and
      the polarization state of the STED beam. We present a simple theoretical
      framework that help to explain their influence on the performance of a STED
      microscope and we validate the results by imaging calibration and biological
      samples with a custom made STED architecture based on a supercontinuum laser
      source. We also highlight the advantages of using time gating detection in terms
      of temporal alignment.

PMID- 22453417
TI  - Referenced passive spectroscopy using dual frequency combs.
AB  - A referenced passive spectroscopy scheme using infrared frequency combs is
      presented. We perform a noise analysis and compare the results with a classical
      Fourier transform spectrometer. Experimental results are shown and great
      agreement with theory is obtained.

PMID- 22453418
TI  - Confocal surface plasmon microscopy with pupil function engineering.
AB  - Surface Plasmon microscopy can measure local changes of refractive index on the
      micron scale. Interferometric plasmon imaging delivers quantitative high spatial
      resolution sensitive to refractive index. In addition the so called V(z) method
      allows image contrast to be controlled by varying the sample defocus without
      substantially degrading spatial resolution. Here, we show how a confocal system
      provides a simpler and more stable alternative. This system, however, places
      greater demands on the dynamic range of the system. We therefore use a spatial
      light modulator to engineer the microscope pupil function to suppress light that
      does not contribute to the signal.

PMID- 22453419
TI  - Performance evaluation of photonic UWB generation based on silicon MZM.
AB  - Silicon photonics has emerged as the premier candidate for the photonic systems
      on-chip (SoC). The scheme based on the silicon Mach-Zehnder modulator (MZM) to
      generate photonic ultra-wideband (UWB) signals is helpful to the integration of
      the UWB system with other optical networks on a single silicon-based chip. In
      this paper, according to the influence of the nonlinear free carrier dispersion
      (FCD) effect and the free carrier absorption (FCA) effect, the performance of two
      typical UWB generation schemes is numerically analyzed. The double side-band UWB
      (DSB-UWB) generation scheme needs the DC reverse bias which increases the
      complexity of the modulator and there is a residual chirp resulting from the FCD
      effect even the push-pull operation is adopted. The quasi single-sideband UWB
      (QSSB-UWB) generation scheme doesn't have these problems. However there is the
      asymmetric amplitude peak in the generated UWB signal. The property of the large
      singal modulation is also investigated to improve the signal-to-noise ratio
      (SNR).

PMID- 22453420
TI  - High speed silicon microring modulator employing dynamic intracavity energy
      balance.
AB  - High speed coupling-modulation of a microring-based light drop structure is
      proposed, which removes severe signal distortion due to intracavity energy
      depletion and separates the modulation speed from the resonator linewidth
      restriction. Extinction ratio improvement from <1 dB to >20 dB with 40 Gb/s non
      return-to-zero (NRZ) signals is obtained with 25 times smaller drive voltage. The
      tolerance to active ring propagation loss is increased from 5 dB/cm to over 25
      dB/cm with less than 5% modulation bandwidth reduction. The possibility of
      obtaining 160 Gb/s NRZ signal with no more than 4 V drive voltage and less than 5
      dB insertion loss is highlighted.

PMID- 22453421
TI  - SCPEM-Q-switching of a fiber-rod-laser.
AB  - We demonstrate high-frequency Q-switching of a fiber rod laser with a Single
      Crystal Photo-Elastic Modulator (SCPEM) made of a LiTaO3- crystal. This type of
      photo-elastic modulator can be driven simultaneously with two different
      eigenmodes to achieve a shorter rise time, which is essential for high-power
      operation. When operated in the laser cavity, a pulse repetition frequency of
      183.6 kHz with an average power of 47 W, a pulse duration of 26 ns, and a peak
      power of 10.5 kW was achieved.

PMID- 22453422
TI  - Coherent combining of pulsed fiber amplifiers in the nonlinear chirp regime with
      intra-pulse phase control.
AB  - Two high pulse contrast (> 95 dB) polarization maintaining all-fiber amplifier
      chains were coherently combined to generate 0.42 mJ, 1 ns 25 kHz pulses with 79%
      efficiency despite 38 radians of intra-pulse phase distortion. A recursive intra
      pulse phase compensation method was utilized to correct for the large nonlinear
      chirp providing a path for improved coherent waveform control of nanosecond pulse
      trains.

PMID- 22453423
TI  - Investigating the effectiveness of thermally poling optical fibers with various
      internal electrode configurations.
AB  - Twin-hole fibers were thermally poled with different internal electrode
      configurations, including having only one anode wire in the hole, two anode wires
      in the two holes, one cathode wire, and two cathode wires in the holes, in
      comparison to the conventional one anode wire and one cathode wire combination.
      Second harmonic microscopy was utilized to visually reveal the spatial
      distribution and to measure the magnitude of the induced second-order optical
      nonlinearity within the poled fibers. It was found that both one- and two-anode
      configurations resulted in strong nonlinearity comparable with the conventional
      case but the two-anode configuration was more reproducible than the one-anode
      case; for the one-cathode-wire and two-cathode-wire configuration, strong
      nonlinearity in a ring shape concentric with the fiber outer surface was induced
      as if the cathode metal wire were in the center of the twin-hole fiber rather
      than substantially offset. These new results provide strong support for the
      proposed model of a "self-adjustment" mechanism and point the way to simplified
      and more repeatable experimental techniques.

PMID- 22453424
TI  - Porous SiO2/MgF2 broadband antireflection coatings for superstrate-type silicon
      based tandem cells.
AB  - The purpose of this study is to reduce the glass substrate reflectivity over a
      wide spectral range (400-1200 nm) without having high reflectivity in the near
      infrared region. After making porous SiO2/MgF2 double-layer antireflection (DLAR)
      thin film structure, the superstrate-type silicon-based tandem cells are added.
      In comparison to having only silicon-based tandem solar cells, the short-circuit
      current density has improved by 6.82% when porous SiO2/MgF2 DLAR thin film is
      applied to silicon-based tandem solar cells. This study has demonstrated that
      porous SiO2/MgF2 DLAR thin film structure provides antireflection properties over
      a broad spectral range (400-1200 nm) without having high reflectivity at near
      infrared wavelengths.

PMID- 22453425
TI  - Bistability and self-pulsation phenomena in silicon microring resonators based on
      nonlinear optical effects.
AB  - Bistability (BS) and self-pulsation (SP) phenomena in silicon microring
      resonators (MRR) with intense CW light injection are studied. Several nonlinear
      optical effects including Kerr effect, two-photon absorption, free carrier
      absorption and free carrier dispersion are taken into account. The threshold
      optical intensity of BS and SP is derived from the coupled mode theory and a
      linear stability analysis method. The influences of MRR's parameters (carrier
      lifetime, linear loss and radius) and light injection conditions (input power,
      wavelength detuning) on the characteristics of SP (modulation depth and
      oscillating frequency) are analyzed and discussed. It is shown that, SP occurs
      only if the carrier lifetime ranges from several ps to several-hundred ps and the
      input light intensity is higher than 106W/cm2. The modulation depth of SP can be
      as large as 8dB and the associated oscillating frequency is in the range from
      several GHz to beyond 10 GHz.

PMID- 22453426
TI  - Solitons in nonlocal nonlinear Kerr media with exponential response function.
AB  - In this paper, we find some exact analytical solutions including bright soliton
      solution, dipole-mode soliton solution, double soliton solution and periodic
      solution when a slit laser beam propagates in Kerr-type nonlinear, nonlocal media
      with exponential response function. Furthermore, we address the energy flow is a
      monotonically growing function of d2 and the Hamiltonian decreases while the
      energy flow increases. And we also obtain an Airy-like soliton by numerical
      method.

PMID- 22453427
TI  - Alternative laser system for cesium magneto-optical trap via optical injection
      locking to sideband of a 9-GHz current-modulated diode laser.
AB  - By optical injection of an 852-nm extended-cavity diode laser (master laser) to
      lock the + 1-order sideband of a ~9-GHz-current-modulated diode laser (slave
      laser), we generate a pair of phase-locked lasers with a frequency difference up
      to ~9-GHz for a cesium (Cs) magneto-optical trap (MOT) with convenient tuning
      capability. For a cesium MOT, the master laser acts as repumping laser, locked to
      the Cs 6S1/2 (F = 3) - 6P3/2 (F' = 4) transition. When the + 1-order sideband of
      the 8.9536-GHz-current-modulated slave laser is optically injection-locked, the
      carrier operates on the Cs 6S1/2 (F = 4) - 6P3/2 (F' = 5) cooling cycle
      transition with -12 MHz detuning and acts as cooling/trapping laser. When
      carrying a 9.1926-GHz modulation signal, this phase-locked laser system can be
      applied in the fields of coherent population trapping and coherent manipulation
      of Cs atomic ground states.

PMID- 22453428
TI  - Si/Ge uni-traveling carrier photodetector.
AB  - We have fabricated and characterized a germanium on silicon uni-traveling carrier
      photodetector for analog and coherent communications applications. The device has
      a bandwidth of 20GHz, a large-signal 1dB saturation photocurrent of 20mA at -3V,
      and a low thermal impedance of 520K/W.

PMID- 22453429
TI  - A robust random number generator based on differential comparison of chaotic
      laser signals.
AB  - We experimentally realize a robust real-time random number generator by
      differentially comparing the signal from a chaotic semiconductor laser and its
      delayed signal through a 1-bit analog-to-digital converter. The probability
      density distribution of the output chaotic signal based on the differential
      comparison method possesses an extremely small coefficient of Pearson's median
      skewness (1.5 * 10-6), which can yield a balanced random sequence much easily
      than the previously reported method that compares the signal from the chaotic
      laser with a certain threshold value. Moveover, we experimently demonstrate that
      our method can stably generate good random numbers at rates of 1.44 Gbit/s with
      excellent immunity from external perturbations while the previously reported
      method fails.

PMID- 22453430
TI  - Spectral properties of high-gain parametric down-conversion.
AB  - High-gain parametric down-conversion (PDC) is a source of bright squeezed vacuum,
      which is a macroscopic nonclassical state of light and a promising candidate for
      quantum information applications. Here we study its properties, such as the
      intensity spectral width and the spectral width of pairwise correlations. In
      agreement with the theory, we observe an increase in the spectral width by 27%
      compared with the low-gain PDC. Frequency cross- and auto-correlations are
      registered by measuring the reduction of noise in the difference of PDC
      intensities at various pairs of wavelengths. The noise reduction plots also
      demonstrate super-bunching typical for collinear frequency-degenerate PDC.

PMID- 22453431
TI  - Selective-mode optical nanofilters based on plasmonic complementary split-ring
      resonators.
AB  - A nanoplasmonic optical filtering technique based on a complementary split-ring
      resonator structure is proposed. The basic and modal properties of the square
      nanoring are studied using the group theory. Degeneracy and non-degeneracy of the
      possible TM odd- and even-modes are characterized based on the symmetry elements
      of the ring structure. Distinctively, the proposed technique allows selecting and
      exciting the proper plasmonic modes of the nanoring in the side-coupled
      arrangement. It is found that the non-integer modes can be excited due to the
      presence of a metallic nano-wall. These modes are highly sensitive to the nano
      wall dimensions, in contrast to the regular integer modes. Moreover, the
      transmission-line theory is used to derive the resonance condition of the modes.
      The results show the optical transmission spectrum of the investigated filter can
      be efficiently modified and tuned either by manipulation of the position or by
      variation of the width of the employed nano-wall inside the ring. The numerical
      results support the theoretical analysis.

PMID- 22453432
TI  - High-efficiency second-harmonic generation in doubly-resonant chi(2) microring
      resonators.
AB  - By directly simulating Maxwell's equations via the finite-difference time-domain
      (FDTD) method, we numerically demonstrate the possibility of achieving high
      efficiency second harmonic generation (SHG) in a structure consisting of a
      microscale doubly-resonant ring resonator side-coupled to two adjacent
      waveguides. We find that ? 94% conversion efficiency can be attained at telecom
      wavelengths, for incident powers in the milliwatts, and for reasonably large
      bandwidths (Q ~ 1000s). We demonstrate that in this high efficiency regime, the
      system also exhibits limit-cycle or bistable behavior for light incident above a
      threshold power. Our numerical results agree to within a few percent with the
      predictions of a simple but rigorous coupled-mode theory framework.

PMID- 22453433
TI  - Transmission of PM-QPSK and PS-QPSK with different fiber span lengths.
AB  - We perform experimental and numerical investigations of the transmission reach of
      polarization-switched QPSK (PS-QPSK) and polarization-multiplexed QPSK (PM-QPSK)
      for three different fiber span lengths: 83, 111 and 136 km. In the experimental
      comparison we investigate the performance of PS-QPSK at 20 Gbaud and PM-QPSK at
      the same bit rate (60 Gbit/s) and at the same symbol rate, both the single
      channel case and a WDM system with 9 channels on a 50 GHz grid. We show that PS
      QPSK gives significant benefits in transmission reach for all span lengths.
      Compared to PM-QPSK, use of PS-QPSK increases the reach with more than 41% for
      the same symbol rate and 21% for the same bit rate. In the numerical simulations
      we use the same data rates as in the experiment. The simulation results agree
      well with the experimental findings, but the transmission reach is longer due to
      the absence of various non-ideal effects and higher back-to-back sensitivity.
      Apart from using data coded in the absolute phase in the simulations, we also
      investigate differentially coded PS-QPSK for the first time and compare with PM
      QPSK with differential coding. The power efficiency advantage of PS-QPSK then
      increases with approximately 0.3 dB at a bit error rate of 10-3, resulting in a
      further relative transmission reach improvement over PM-QPSK. Both the
      experimental and the numerical results indicate that PS-QPSK has slightly higher
      tolerance to inter-channel nonlinear crosstalk than PM-QPSK.

PMID- 22453434
TI  - Adaptive synthetic-aperture focusing technique for microvasculature imaging using
      photoacoustic microscopy.
AB  - To improve the lateral resolution of the blood vessels along arbitrary direction
      out of focus in photoacoustic microscopy (PAM), we propose an adaptive synthetic
      aperture focusing technique (ASAFT) for microvasculature imaging which can be
      automatically applied to each branch of blood vessels, based on our previous two
      dimensional (2D) SAFT. The ASAFT is validated both in the phantom study and in
      vivo imaging. The results demonstrate that ASAFT can provide images of blood
      vessels with better lateral resolution both at different depths and along various
      directions compared with one-dimensional and 2D SAFT.

PMID- 22453435
TI  - Automated measurement of choroidal thickness in the human eye by polarization
      sensitive optical coherence tomography.
AB  - We present a new method to automatically segment the thickness of the choroid in
      the human eye by polarization sensitive optical coherence tomography (PS-OCT). A
      swept source PS-OCT instrument operating at a center wavelength of 1040 nm is
      used. The segmentation method is based entirely on intrinsic, tissue specific
      polarization contrast mechanisms. In a first step, the anterior boundary of the
      choroid, the retinal pigment epithelium, is segmented based on depolarization. In
      a second step, the choroid-sclera interface is found by using the birefringence
      of the sclera. The method is demonstrated in five healthy eyes. The mean
      repeatability (standard deviation) of thickness measurement was found to be 18.3
      um.

PMID- 22453436
TI  - Broadband and omnidirectional light harvesting enhancement of fluorescent SiC.
AB  - In the present work, antireflective sub-wavelength structures have been
      fabricated on fluorescent 6H-SiC to enhance the white light extraction efficiency
      by using the reactive-ion etching method. Broadband and omnidirectional
      antireflection characteristics show that 6H-SiC with antireflective sub
      wavelength structures suppress the average surface reflection significantly from
      20.5 % to 1.01 % over a wide spectral range of 390-784 nm. The luminescence
      intensity of the fluorescent 6H-SiC could be enhanced in the whole emission angle
      range. It maintains an enhancement larger than 91 % up to the incident angle of
      70 degrees, while the largest enhancement of 115.4 % could be obtained at 16
      degrees. The antireflective sub-wavelength structures on fluorescent 6H-SiC could
      also preserve the luminescence spectral profile at a large emission angle by
      eliminating the Fabry-Perot microcavity interference effect.

PMID- 22453437
TI  - Ultra-broad and sharp-transition bandpass terahertz filters by hybridizing
      multiple resonances mode in monolithic metamaterials.
AB  - We present three monolithic metamaterial-based THz bandpass filters, the skewed
      circular slot rings, meandered slots and Jerusalem cross slots, to fit in the THz
      gap. These THz bandpass filters are comprised of a metal-dielectric-metal (MDM)
      structure that supports multiple resonances of electric dipole, magnetic dipole,
      and standing-wave-like modes. By exciting and further hybridizing these
      individual resonance modes, we demonstrate excellent performance of broad
      bandwidth and sharp band-edge transition beyond conventional bandpass filters. By
      further employing our ad hoc Genetic Algorithm (GA) and Periodic Method of
      Moments (PMM) to optimize our designs, we achieve an ultra-broad 3dB fractional
      bandwidth and sharp band-edge transition up to 82.2% and 58.3 dB/octave,
      respectively, benefiting the practical applications such as material recognition
      in security systems, imaging, and absorbers.

PMID- 22453438
TI  - Real-time measurements of atmospheric CO using a continuous-wave room temperature
      quantum cascade laser based spectrometer.
AB  - A compact, mobile mid-infrared laser spectrometer based on a thermoelectrically
      (TE) cooled continuous-wave room temperature quantum cascade laser and TE-cooled
      detectors has been newly developed to demonstrate the applicability of high
      sensitivity and high precision measurements of atmospheric CO. Performance of the
      instrument was examined with periodic measurements of reference sample and
      ambient air at 1 Hz sampling rate and a 1-hourly calibration cycle. The typical
      precision evaluated from replicate measurements of reference sample over the
      course of 66-h is 1.41 ppbv. With the utilization of wavelet filtering to improve
      the spectral SNR and minimize the dispersion of concentration values, a better
      precision of 0.88 ppbv and a lower detection limit of ~0.4 ppbv with sub-second
      averaging time have been achieved without reducing the fast temporal response.
      Allan variance analysis indicates a CO measurement precision of ~0.28 ppbv for
      optimal integration time of approximate 50 s. The absolute accuracy is limited by
      the calibration gas standard. This completely thermoelectrically cooled system
      shows the capability of long-term, unattended and continuous operation at room
      temperature without complicated cryogenic cooling.

PMID- 22453439
TI  - Improved 800 nm emission of Tm3+ sensitized by Yb3+ and Ho3+ in beta-NaYF4
      nanocrystals under 980 nm excitation.
AB  - In vitro and in vivo bioimaging, Yb/Tm doped fluoride nanocrystals (NCs) as
      nanoprobes have attracted much attention due to their near infrared (NIR)
      upconversion (UC) emission at 800 nm under NIR 980 nm excitation. Our paper
      presents a simple and general method which can further improve the intensity of
      NIR 800 nm emission of Tm3+ through adding Ho3+ as the second sensitizer of Tm3+
      in Yb/Tm doped NaYF4 nanorods. The intensity of the NIR 800 nm emission is
      demonstrated to increase by up to 3 times along with the adding of Ho3+.
      Experimental data illustrates that the sensitizations of Tm3+ by both Yb3+ and
      Ho3+ provide a more efficient energy transfer (ET) route for intense 800 nm
      emission than that by Yb3+ alone.

PMID- 22453440
TI  - Silicon-Germanium multi-quantum well photodetectors in the near infrared.
AB  - Single crystal Silicon-Germanium multi-quantum well layers were epitaxially grown
      on silicon substrates. Very high quality films were achieved with high level of
      control utilizing recently developed MHAH epitaxial technique. MHAH growth
      technique facilitates the monolithic integration of photonic functionality such
      as modulators and photodetectors with low-cost silicon VLSI technology. Mesa
      structured p-i-n photodetectors were fabricated with low reverse leakage currents
      of ~10 mA/cm2 and responsivity values exceeding 0.1 A/W. Moreover, the spectral
      responsivity of fabricated detectors can be tuned by applied voltage.

PMID- 22453441
TI  - Design of mid-infrared amplifiers based on fiber taper coupling to erbium-doped
      microspherical resonator.
AB  - A dedicated 3D numerical model based on coupled mode theory and solving the rate
      equations has been developed to analyse, design and optimize an optical amplifier
      obtained by using a tapered fiber and a Er3+-doped chalcogenide microsphere. The
      simulation model takes into account the main transitions among the erbium energy
      levels, the amplified spontaneous emission and the most important secondary
      transitions pertaining to the ion-ion interactions. The taper angle of the
      optical fiber and the fiber-microsphere gap have been designed to efficiently
      inject into the microsphere both the pump and the signal beams and to improve
      their spatial overlapping with the rare earth doped region. In order to reduce
      the computational time, a detailed investigation of the amplifier performance has
      been carried out by changing the number of sectors in which the doped area is
      partitioned. The simulation results highlight that this scheme could be useful to
      develop high efficiency and compact mid-infrared amplifiers.

PMID- 22453442
TI  - Detailed validation of the bidirectional effect in various Case I and Case II
      waters.
AB  - Simulated bidirectional reflectance distribution functions (BRDF) were compared
      with measurements made just beneath the water's surface. In Case I water, the set
      of simulations that varied the particle scattering phase function depending on
      chlorophyll concentration agreed more closely with the data than other models. In
      Case II water, however, the simulations using fixed phase functions agreed well
      with the data and were nearly indistinguishable from each other, on average. The
      results suggest that BRDF corrections in Case II water are feasible using single,
      average, particle scattering phase functions, but that the existing approach
      using variable particle scattering phase functions is still warranted in Case I
      water.

PMID- 22453443
TI  - Comparative intrinsic optical signal imaging of wild-type and mutant mouse
      retinas.
AB  - Functional measurement is important for retinal study and disease diagnosis.
      Transient intrinsic optical signal (IOS) response, tightly correlated with
      functional stimulation, has been previously detected in normal retinas. In this
      paper, comparative IOS imaging of wild-type (WT) and rod-degenerated mutant mouse
      retinas is reported. Both 2-month and 1-year-old mice were measured. In 2-month
      old mutant mice, time course and peak value of the stimulus-evoked IOS were
      significantly delayed (relative to stimulus onset) and reduced, respectively,
      compared to age matched WT mice. In 1-year-old mutant mice, stimulus-evoked IOS
      was totally absent. However, enhanced spontaneous IOS responses, which might
      reflect inner neural remodeling in diseased retina, were observed in both 2-month
      and 1-year-old mutant retinas. Our experiments demonstrate the potential of using
      IOS imaging for noninvasive and high resolution identification of disease
      associated retinal dysfunctions. Moreover, high spatiotemporal resolution IOS
      imaging may also lead to advanced understanding of disease-associated neural
      remodeling in the retina.

PMID- 22453444
TI  - 0.48Tb/s (12x40Gb/s) WDM transmission and high-quality thermo-optic switching in
      dielectric loaded plasmonics.
AB  - We demonstrate Wavelength Division Multiplexed (WDM)-enabled transmission of
      480Gb/s aggregate data traffic (12x40Gb/s) as well as high-quality 1x2 thermo
      optic tuning in Dielectric-Loaded Surface Plasmon Polariton Waveguides (DLSPPWs).
      The WDM transmission characteristics have been verified through BER measurements
      by exploiting the heterointegration of a 60 MUm-long straight DLSPPW on a Silicon
      on-Insulator waveguide platform, showing error-free performance for six out of
      the twelve channels. High-quality thermo-optic tuning has been achieved by
      utilizing Cycloaliphatic-Acrylate-Polymer as an efficient thermo-optic polymer
      loading employed in a dual-resonator DLSPPW switching structure, yielding a 9 nm
      wavelength shift and extinction ratio values higher than 10 dB at both output
      ports when heated to 90 degrees C.

PMID- 22453445
TI  - Chirp-free optical return-to-zero modulation based on a single microring
      resonator.
AB  - This paper proposes a chirp-free optical return-to-zero (RZ) modulator using a
      double coupled microring resonator. Optical RZ modulation is achieved by applying
      a clock (CLK) driving signal to the input coupling region and a non-return-to
      zero (NRZ) driving signal to the output coupling region. Static and time-domain
      coupled-mode theory (CMT) based dynamic analyse are performed to theoretically
      investigate its performance in RZ modulation. The criteria to realize RZ
      modulation are deduced. Various RZ modulation formats, including RZ phase-shift
      keying (RZ-PSK), carrier-suppressed RZ (CSRZ), and RZ intensity modulation
      formats, can be implemented by using CLK and NRZ signals with different
      combinations of polarities. Numerical simulations are performed and the
      feasibility of our modulator at 10 Gbit/s for the multiple RZ modulation formats
      is verified.

PMID- 22453446
TI  - Optomechanically induced non-reciprocity in microring resonators.
AB  - We describe a new approach for on-chip optical non-reciprocity which makes use of
      strong optomechanical interaction in microring resonators. By optically pumping
      the ring resonator in one direction, the optomechanical coupling is only enhanced
      in that direction, and consequently, the system exhibits a non-reciprocal
      response. For different configurations, this system can function either as an
      optical isolator or a coherent non-reciprocal phase shifter. We show that the
      operation of such a device on the level of single-photon could be achieved with
      existing technology.

PMID- 22453447
TI  - Collective behavior of impedance matched plasmonic nanocavities.
AB  - Nanometer sized cavities arranged as a subwavelength metallic grating can provide
      omni-directional and complete absorption of light. We present an explanation of
      this extraordinary phenomenon as a collective resonant response of a system based
      on a surface impedance model. This model gives a straightforward way to design
      systems for optimum light trapping performance and as well gives fundamental
      insights into the interaction of light with metals at the nanoscale.

PMID- 22453449
TI  - Coaxial waveguide mode reconstruction and analysis with THz digital holography.
AB  - Terahertz (THz) digital holography is employed to investigate the properties of
      waveguides. By using a THz digital holographic imaging system, the propagation
      modes of a metallic coaxial waveguide are measured and the mode patterns are
      restored with the inverse Fresnel diffraction algorithm. The experimental results
      show that the THz propagation mode inside the waveguide is a combination of four
      modes TE11, TE12, TM11, and TM12, which are in good agreement with the simulation
      results. In this work, THz digital holography presents its strong potential as a
      platform for waveguide mode charactering. The experimental findings provide a
      valuable reference for the design of THz waveguides.

PMID- 22453448
TI  - High-resolution imaging of microvasculature in human skin in-vivo with optical
      coherence tomography.
AB  - In this paper, the features of the intensity-based Doppler variance (IBDV) method
      were analyzed systemically with a flow phantom. The effects of beam scanning
      density, flow rate and the time interval between neighboring A-lines on the
      performance of this method were investigated. The IBDV method can be used to
      quantify the flow rate and its sensitivity can be improved by increasing the time
      interval between the neighboring A-lines. A higher sensitivity IBDV method that
      applies the algorithm along the slower scan direction was proposed. In comparison
      to laser speckle imaging maps of blood flow, we demonstrated the ability of the
      method to identify vessels with altered blood flow. In clinical measurements, we
      demonstrated the ability of the method to image vascular networks with exquisite
      spatial resolution and at depths up to 1.2 mm in human skin. These results
      collectively demonstrated the potential of the method to monitor the
      microvasculature during disease progression and in response to therapeutic
      intervention.

PMID- 22453450
TI  - Highly nonlinear fiber with dispersive characteristic invariant to fabrication
      fluctuations.
AB  - New class of highly nonlinear fibers possessing dispersive characteristics
      invariant to transverse geometry fluctuations is described. The sensitivity to
      stochastic core fluctuations is reduced by order of magnitude while maintaining
      the fiber nonlinear coefficient. The effectiveness of the new highly nonlinear
      fiber type is demonstrated on stochastically perturbed distant-band mixer that
      could not be previously constructed with high-confinement fiber. The new fiber
      design offers a unique platform for ideally phase matched parametric exchange
      with significantly increased Brillouin threshold.

PMID- 22453451
TI  - Plasmonic band structures and optical properties of subwavelength
      metal/dielectric/metal Bragg waveguides.
AB  - In this paper, we applied the band structure theory to investigate the plasmonic
      band (PB) structures and optical properties of subwavelength
      metal/dielectric/metal Bragg waveguides in the near infrared range with either
      dielectric or geometric modulation. The Bloch wave vector, density of states,
      slowdown factor, propagation length and transmittance are calculated and
      analyzed. Both the modulations are in favor of manipulating surface-plasmon
      polariton (SPP) waves. For the dielectric modulation, the PB structure is mainly
      formed by SPP modes and possesses a "regular pattern" in which the bands and gaps
      have a relatively even distribution. For the geometric modulation, due to the
      strong transverse scattering, the contributions of higher modes have to be
      considered and the gap widths have a significant increase compared to the
      dielectric modulation. A larger slowdown factor may emerge at the band edge;
      especially for the geometric modulation, the group velocity can be reduced to
      1/100 of light, and negative group velocity is observed as well. While inside the
      bands, the slowdown factor is smaller and the bands are flat. The contribution of
      each eigenmode to the PB structure is analyzed.

PMID- 22453452
TI  - Unconventional structure-assisted optical manipulation of high-index nanowires in
      liquid crystals.
AB  - Stable optical trapping and manipulation of high-index particles in low-index
      host media is often impossible due to the dominance of scattering forces over
      gradient forces. Here we explore optical manipulation in liquid crystalline
      structured hosts and show that robust optical manipulation of high-index
      particles, such as GaN nanowires, is enabled by laser-induced distortions in long
      range molecular alignment, via coupling of translational and rotational motions
      due to helicoidal molecular arrangement, or due to elastic repulsive interactions
      with confining substrates. Anisotropy of the viscoelastic liquid crystal medium
      and particle shape give rise to a number of robust unconventional trapping
      capabilities, which we use to characterize defect structures and study
      rheological properties of various thermotropic liquid crystals.

PMID- 22453453
TI  - Temporal broadening of optical pulses propagating through non-Kolmogorov
      turbulence.
AB  - General formulations of the temporal averaged pulse intensity for optical pulses
      propagating through either non-Kolmogorov or Kolmogorov turbulence are deduced
      under the strong fluctuation conditions and the narrow-band assumption. Based on
      these formulations, an analytical formula for the turbulence-induced temporal
      half-width of spherical-wave Gaussian (SWG) pulses is derived, and the single
      point, two-frequency mutual coherence function (MCF) of collimated Gaussian-beam
      waves in atmospheric turbulence is formulated analytically, by which the temporal
      averaged pulse intensity of collimated space-time Gaussian (CSTG) pulses can be
      calculated numerically. Calculation results show that the temporal broadening of
      both SWG and CSTG pulses in atmospheric turbulence depends heavily on the general
      spectral index of the spatial power spectrum of refractive-index fluctuations,
      and the temporal broadening of SWG pulses can be used to approximate that of CSTG
      pulses on the axis with the same turbulence parameters and propagation distances.
      It is also illustrated by numerical calculations that the variation in the
      turbulence-induced temporal half-width of CSTG pulses with the radial distance is
      really tiny.

PMID- 22453454
TI  - Monolithic integration of III-V nanowire with photonic crystal microcavity for
      vertical light emission.
AB  - A novel photonic structure formed by the monolithic integration of a vertical III
      V nanowire on top of a L3 two-dimensional photonic crystal microcavity is
      proposed to enhance light emission from the nanowire. The impact on the nanowire
      spontaneous emission rate is evaluated by calculating the spontaneous emission
      factor beta, and the material gain at threshold is used as a figure of merit of
      this vertical emitting nanolaser. An optimal design is identified for a GaAs
      nanowire geometry with r = 155 nm and L~1.1 MUm, where minimum gain at threshold
      (gth~13*103 cm-1) and large spontaneous emission factor (beta~0.3) are
      simultaneously achieved. Modification of the directivity of the L3 photonic
      crystal cavity via the band-folding principle is employed to further optimize the
      far-field radiation pattern and to increase the directivity of the device. These
      results lay the foundation for a new approach toward large-scale integration of
      vertical emitting nanolasers and may enable applications such as intra-chip
      optical interconnects.

PMID- 22453455
TI  - Partial loss compensation in dielectric-loaded plasmonic waveguides at near infra
      red wavelengths.
AB  - We report on the fabrication and characterization of straight dielectric-loaded
      surface plasmon polaritons waveguides doped with lead-sulfide quantum dots as a
      near infra-red gain medium. A loss compensation of ~33% (an optical gain of ~143
      cm-1) was observed in the guided mode. The mode propagation, coupling efficiency
      and stimulated emission were characterized using leakage radiation microscopy.
      The guided mode signature was separated using spatial filters in the Fourier
      plane of the microscope for quantitative measurements of stimulated emission.

PMID- 22453456
TI  - Modeling nonlinearity in coherent transmissions with dominant intrachannel-four
      wave-mixing.
AB  - By extending a well-established time-domain perturbation approach to dual
      polarization propagation, we provide an analytical framework to predict the
      nonlinear interference (NLI) variance, i.e., the variance induced by nonlinearity
      on the sampled field, and the nonlinear threshold (NLT) in coherent transmissions
      with dominant intrachannel-four-wave-mixing (IFWM). Such a framework applies to
      non dispersion managed (NDM) very long-haul coherent optical systems at nowadays
      typical baudrates of tens of Gigabaud, as well as to dispersion-managed (DM)
      systems at even higher baudrates, whenever IFWM is not removed by nonlinear
      equalization and is thus the dominant nonlinearity. The NLI variance formula has
      two fitting parameters which can be calibrated from simulations. From the NLI
      variance formula, analytical expressions of the NLT for both DM and NDM systems
      are derived and checked against recent NLT Monte-Carlo simulations.

PMID- 22453457
TI  - Decelerating a pulsed subsonic molecular beam by a quasi-cw traveling optical
      lattice.
AB  - We propose a promising scheme to realize the deceleration of a pulsed subsonic
      molecular beam by using a multistage optical Stark decelerator (i.e., a 1D quasi
      cw traveling optical lattice), which is composed of two nearly counter
      propagating, time-varying, red-detuned light fields with an intensity of ~107Wcm
      2 and a fixed frequency difference between them. We also study the influence of
      the velocity reduced amount of the traveling lattice, the lattice power, the
      synchronous phase angle, the deceleration-stage number and the temporal profile
      of laser pulses on the molecular slowing results by using 3D Monte-Carlo method.
      Our study shows that the proposed decelerator cannot only be used to slow a
      pulsed subsonic beam from 240m/s to standstill, but also to obtain a cold
      molecular packet with a temperature of a few uK, and the corresponding fraction
      of cold molecules is 10-6-10-7, which strongly depends on the synchronous phase
      angle. And we also find that a pair of appropriate rising and falling times of
      laser pulses will lead to a better slowing effect than that produced by the top
      hat temporal ones.

PMID- 22453458
TI  - Localized and stationary dynamic gratings via stimulated Brillouin scattering
      with phase modulated pumps.
AB  - A novel technique for the localization of stimulated Brillouin scattering (SBS)
      interaction is proposed, analyzed and demonstrated experimentally. The method
      relies on the phase modulation of two counter-propagating optical waves by a
      common pseudo-random bit sequence (PRBS), these waves being spectrally detuned by
      the Brillouin frequency shift. The PRBS symbol duration is much shorter than the
      acoustic lifetime. The interference between the two modulated waves gives rise to
      an acoustic grating that is confined to narrow correlation peaks, as short as 1.7
      cm. The separation between neighboring peaks, which is governed by the PRBS
      length, can be made arbitrarily long. The method is demonstrated in the
      generation and applications of dynamic gratings in polarization maintaining (PM)
      fibers. Localized and stationary acoustic gratings are induced by two phase
      modulated pumps that are polarized along one principal axis of the PM fiber, and
      interrogated by a third, readout wave which is polarized along the orthogonal
      axis. Using the proposed technique, we demonstrate the variable delay of 1 ns
      long readout pulses by as much as 770 ns. Noise due to reflections from residual
      off-peak gratings and its implications on the potential variable delay of optical
      communication data are discussed. The method is equally applicable to the
      modulation of pump and probe waves in SBS over standard fibers.

PMID- 22453459
TI  - Determination of wavefront structure for a Hartmann wavefront sensor using a
      phase-retrieval method.
AB  - We apply a phase retrieval algorithm to the intensity pattern of a Hartmann
      wavefront sensor to measure with enhanced accuracy the phase structure of a
      Hartmann hole array. It is shown that the rms wavefront error achieved by phase
      reconstruction is one order of magnitude smaller than the one obtained from a
      typical centroid algorithm. Experimental results are consistent with a phase
      measurement performed independently using a Shack-Hartmann wavefront sensor.

PMID- 22453460
TI  - Spatially distributed successive approximation register (SDSAR) photonic ADCs
      based on phase-domain quantization.
AB  - We explore photonic ADC architectures based on encoding voltage-under-test into
      phase. The first step is to identify two basic optical building blocks: the
      optical phase comparator (1-bit ADC), based on interferometric comparison of
      phases in the well-known balanced photo-detection configuration, and the optical
      1-bit DAC, namely electro-optic modulation with a bipolar electrical pulse.
      Equipped with these fundamental building blocks, we proceed to systematically
      port and adapt known ADC quantization architectures to photonic ADC, conceiving a
      hybrid between the Successive Approximation Register (SAR) and the Pipeline
      classic ADC architectures, referred to here as Spatially Distributed SAR (SDSAR).
      This novel photonic ADC, constructed out of B 1-bit ADCs and B-2 1-bit DACs, with
      B the number of bits, is not equivalent to any of the previous photonic ADCs in
      the literature, but appears superior to prior schemes in both optical power
      efficiency and electro-optic modulation complexity. We derive upper bounds on
      resolution, Effective Number of Bits (ENOB) performance as a function of average
      optical power for the new SDSAR device, developing analytic and numeric Monte
      Carlo statistical models, comprising quantization, shot, thermal and DAC voltage
      noise sources. Our findings indicate that SDSAR is limited to ~11.5 ENOBs,
      assuming state-of-the-art mode-locked-lasers providing ~250 mW of average power
      (assuming ~7 dB excess losses). However, this upper bound is not tight, due to
      various physical impairments. In particular, the mode locked laser jitter is
      shown to have negligible impact on overall performance for RMS jitter < 20 fsec.

PMID- 22453461
TI  - High-precision atom localization via controllable spontaneous emission in a cycle
      configuration atomic system.
AB  - A scheme for realizing two-dimensional (2D) atom localization is proposed based
      on controllable spontaneous emission in a coherently driven cycle-configuration
      atomic system. As the spatial-position-dependent atom-field interaction, the
      frequency of the spontaneously emitted photon carries the information about the
      position of the atom. Therefore, by detecting the emitted photon one could obtain
      the position information available, and then we demonstrate high-precision and
      high-resolution 2D atom localization induced by the quantum interference between
      the multiple spontaneous decay channels. Moreover, we can achieve 100%
      probability of finding the atom at an expected position by choosing appropriate
      system parameters under certain conditions.

PMID- 22453462
TI  - Chip-to-chip optical interconnections between stacked self-aligned SOI photonic
      chips.
AB  - Photonic silicon devices are key enabling technologies for next generation High
      Performance Computers. In this paper, we report the possibility to stack and
      optically interconnect SOI based photonic chips for future System-In-Package
      photonic architecture. Combining vertical grating couplers and state-of-the-art
      flip-chip technology, we demonstrated low loss penalties and wide spectral range
      optical interconnections between stacked photonic chips.

PMID- 22453463
TI  - PDM-iRZ-QPSK vs. PS-QPSK at 100 Gbit/s over dispersion-managed links.
AB  - We compare by simulation the performance of 100 Gbit/s PDM-iRZ-QPSK and PS-QPSK
      transmission both in homogeneous and hybrid QPSK/OOK DM links. We detail the
      reasons of the overall performance investigating each nonlinear effect (SPM, XPM
      and XPolM) individually. Moreover, we compare the accuracy of the noise loading
      method with the more realistic use of noisy in-line amplifiers. Results shows
      that i) PDM-iRZ-QPSK and PS-QPSK have same reach in both homogeneous and hybrid
      setups, ii) correct simulations must include distributed ASE.

PMID- 22453464
TI  - Purcell effect in photonic crystal microcavities embedding InAs/InP quantum
      wires.
AB  - The spontaneous emission rate and Purcell factor of self-assembled quantum wires
      embedded in photonic crystal micro-cavities are measured at 80 K by using micro
      photoluminescence, under transient and steady state excitation conditions. The
      Purcell factors fall in the range 1.1 - 2 despite the theoretical prediction of
      ~15.5 for the figure of merit. We explain this difference by introducing a
      polarization dependence on the cavity orientation, parallel or perpendicular with
      respect to the wire axis, plus spectral and spatial detuning factors for the
      emitters and the cavity modes, taking in account the finite size of the quantum
      wires.

PMID- 22453465
TI  - Analysis of soft-decision FEC on non-AWGN channels.
AB  - Soft-decision forward error correction (SD-FEC) schemes are typically designed
      for additive white Gaussian noise (AWGN) channels. In a fiber-optic communication
      system, noise may be neither circularly symmetric nor Gaussian, thus violating an
      important assumption underlying SD-FEC design. This paper quantifies the impact
      of non-AWGN noise on SD-FEC performance for such optical channels. We use a
      conditionally bivariate Gaussian noise model (CBGN) to analyze the impact of
      correlations among the signal's two quadrature components, and assess the effect
      of CBGN on SD-FEC performance using the density evolution of low-density parity
      check (LDPC) codes. On a CBGN channel generating severely elliptic noise clouds,
      it is shown that more than 3 dB of coding gain are attainable by utilizing
      correlation information. Our analyses also give insights into potential
      improvements of the detection performance for fiber-optic transmission systems
      assisted by SD-FEC.

PMID- 22453466
TI  - Curvature effects on optical emission of flexible organic light-emitting diodes.
AB  - We present an analytical model for the optical emission of a two-dimensional
      source in a flexible organic light-emitting diode formation with arbitrary
      curvature. The formulation rigorously produces closed-form analytical expressions
      which clearly relate the emission pattern and the device configuration, in
      particular, the radius of curvature. We investigate the optical properties of a
      prototype model through the resultant expressions, revealing that the bending
      induces a dramatic enhancement of emission to large angles, allowing for large
      viewing angle and reduced total internal reflection losses. These effects, shown
      to arise from geometrical considerations, demonstrate the unique advantages which
      curved flexible devices offer with respect to their planar counterparts. To the
      best of our knowledge, this is the first time that a rigorous analytical
      investigation of the optical characteristics of these novel devices is conducted.
      The resultant analytical formulae provide a robust basis for future analysis, as
      well as a set of design rules for efficient device engineering.

PMID- 22453467
TI  - Subwavelength cylindrical grating by holistic phase-mask coordinate transform.
AB  - A periodic grating with an integer number of periods is fabricated at the resist
      coated wall of a cylinder by exposing a circularly symmetrical planar high index
      phase mask to a cylindrical wave. This extends the spatial coherence features
      easily achievable in a planar 2D space to the 3D space of cylindrical waves and
      elements.

PMID- 22453468
TI  - Photonic-crystal membranes for optical detection of single nano-particles,
      designed for biosensor application.
AB  - A sensor designed to detect bio-molecules is presented. The sensor exploits a
      planar 2D photonic crystal (PC) membrane with sub-micron thickness and through
      holes, to induce high optical fields that allow detection of nano-particles
      smaller than the diffraction limit of an optical microscope. We report on our
      design and fabrication of a PC membrane with a nano-particle trapped inside. We
      have also designed and built an imaging system where an optical microscope and a
      CCD camera are used to take images of the PC membrane. Results show how the
      trapped nano-particle appears as a bright spot in the image. In a first
      experimental realization of the imaging system, single particles with a radius of
      75 nm can be detected.

PMID- 22453470
TI  - MOCRA: a Monte Carlo code for the simulation of radiative transfer in the
      atmosphere.
AB  - This paper describes the radiative transfer model (RTM) MOCRA (MOnte Carlo
      Radiance Analysis), developed in the frame of DOAS (Differential Optical
      Absorption Spectroscopy) to correctly interpret remote sensing measurements of
      trace gas amounts in the atmosphere through the calculation of the Air Mass
      Factor. Besides the DOAS-related quantities, the MOCRA code yields: 1- the
      atmospheric transmittance in the vertical and sun directions, 2- the direct and
      global irradiance, 3- the single- and multiple- scattered radiance for a detector
      with assigned position, line of sight and field of view. Sample calculations of
      the main radiometric quantities calculated with MOCRA are presented and compared
      with the output of another RTM (MODTRAN4). A further comparison is presented
      between the NO2 slant column densities (SCDs) measured with DOAS at Evora
      (Portugal) and the ones simulated with MOCRA. Both comparisons (MOCRA-MODTRAN4
      and MOCRA-observations) gave more than satisfactory results, and overall make
      MOCRA a versatile tool for atmospheric radiative transfer simulations and
      interpretation of remote sensing measurements.

PMID- 22453471
TI  - High numerical aperture hybrid optics for two-photon polymerization.
AB  - We report on an immersion hybrid optics specially designed for focusing
      ultrashort laser pulses into a polymer for direct laser writing via two-photon
      polymerization. The hybrid optics allows for well-corrected focusing over a large
      working distance range of 577 MUm with a numerical aperture (NA) of 1.33 and low
      internal dispersion. We combine the concepts of an aplanatic solid immersion lens
      (ASIL) for achieving a high NA with a diffractive optical element (DOE) for
      correction of aberrations. To demonstrate the improvements for volume structuring
      of the polymer, we compare the achievable structure sizes of our optics with a
      commercially available oil-immersion objective (100x, NA=1.4).

PMID- 22453472
TI  - Extreme ultraviolet multilayer for the FERMI@Elettra free electron laser beam
      transport system.
AB  - In this work we present the design of a Pd/B4C multilayer structure optimized for
      high reflectance at 6.67 nm. The structure has been deposited and also
      characterized along one year in order to investigate its temporal stability. This
      coating has been developed for the beam transport system of FERMI@Elettra Free
      Electron Laser: the use of an additional aperiodic capping layer on top of the
      structure combines the high reflectance with filter properties useful in
      rejecting the fundamental harmonic when the goal is to select the third FEL
      harmonic.

PMID- 22453473
TI  - Optically tunable compensation of nonlinear signal distortion in optical fiber by
      end-span optical phase conjugation.
AB  - We demonstrate a nonlinear signal processing approach for compensating nonlinear
      distortion caused by the Kerr effect in optical fiber transmission. The concept
      relies on propagating the signal through a separate all-optical module outside
      the link to apply tunable nonlinear distortion and phase-conjugation in series.
      We show this uniquely enables tunable regeneration of phase-encoded 40 Gb/s
      signals of different data-formats and number of WDM channels, to allow
      significantly higher transmission powers through single and multi-span fiber
      links. An improvement in the receiver power penalty by 3~4 dB for a bit-error
      rate (BER) of ~10-5 is achieved.

PMID- 22453474
TI  - Multiplication theory for dynamically biased avalanche photodiodes: new limits
      for gain bandwidth product.
AB  - Novel theory is developed for the avalanche multiplication process in avalanche
      photodiodes (APDs) under time-varying reverse-biasing conditions. Integral
      equations are derived characterizing the statistics of the multiplication factor
      and the impulse-response function of APDs, as well as their breakdown
      probability, all under the assumption that the electric field driving the
      avalanche process is time varying and spatially nonuniform. Numerical
      calculations generated by the model predict that by using a bit-synchronous
      sinusoidal biasing scheme to operate the APD in an optical receiver, the pulse
      integrated gain-bandwidth product can be improved by a factor of 5 compared to
      the same APD operating under the conventional static biasing. The bit
      synchronized periodic modulation of the electric field in the multiplication
      region serves to (1) produce large avalanche multiplication factors with
      suppressed avalanche durations for photons arriving in the early phase of each
      optical pulse; and (2) generate low avalanche gains and very short avalanche
      durations for photons arriving in the latter part of each optical pulse. These
      two factors can work together to reduce intersymbol interference in optical
      receivers without sacrificing sensitivity.

PMID- 22453475
TI  - Continuous-wave mid-infrared intra-cavity singly resonant PPLN-OPO under 880 nm
      in-band pumping.
AB  - We report herein a continuous-wave mid-infrared intra-cavity singly resonant
      optical parametric oscillator (ICSRO) which is the first example of ICSRO that
      utilize in-band pumped Nd-doped vanadate laser as pump source. A 1064 nm Nd:YVO4
      laser in-band pumped by 880 nm LD and a periodically poled lithium niobate (PPLN)
      crystal are employed as the parent pump laser and the nonlinear medium,
      respectively. The idler output wavelength tuning range is 3.66-4.22 um. A maximum
      output power of 1.54 W at 3.66 um is obtained at absorbed pump power of 21.9 W,
      with corresponding optical efficiency being 7.0%. The control experiment of ICSRO
      under 808 nm traditional pumping is also carried out. The results show that in
      band pumped ICSRO has better performance in terms of threshold, power scaling,
      efficiency and power stability than ICSRO traditionally pumped at 808 nm.

PMID- 22453476
TI  - All-optical frequency downconversion technique utilizing a four-wave mixing
      effect in a single semiconductor optical amplifier for wavelength division
      multiplexing radio-over-fiber applications.
AB  - An all-optical frequency downconversion utilizing a four-wave mixing effect in a
      single semiconductor optical amplifier (SOA) was experimentally demonstrated for
      wavelength division multiplexing (WDM) radio-over-fiber (RoF) applications. Two
      WDM optical radio frequency (RF) signals having 155 Mbps differential phase shift
      keying (DPSK) data at 28.5 GHz were simultaneously down-converted to two WDM
      optical intermediate frequency (IF) signals having an IF frequency of 4.5 GHz by
      mixing with an optical local oscillator (LO) signal having a LO frequency of 24
      GHz in the SOA. The bit-error-rate (BER) performance of the RoF up-links with
      different optical fiber lengths employing all-optical frequency downconversion
      was investigated. The receiver sensitivity of the RoF up-link with a 6 km single
      mode fiber and an optical IF signal in an optical double-sideband format was
      approximately -8.5 dBm and the power penalty for simultaneous frequency
      downconversion was approximately 0.63 dB. The BER performance showed a strong
      dependence on the fiber length due to the fiber dispersion. The receiver
      sensitivity of the RoF up-link with the optical IF signal in the optical single
      sideband format was reduced to approximately -17.4 dBm and showed negligible
      dependence on the fiber length.

PMID- 22453477
TI  - Nano-lens diffraction around a single heated nano particle.
AB  - The action of a nanoscopic spherically symmetric refractive index profile on a
      focused Gaussian beam may easily be envisaged as the action of a phase-modifying
      element, i.e. a lens: Rays traversing the inhomogeneous refractive index field
      n(r) collect an additional phase along their trajectory which advances or retards
      their phase with respect to the unperturbed ray. This lens-like action has long
      been understood as being the mechanism behind the signal of thin sample
      photothermal absorption measurements [Appl. Opt. 34, 41-50 (1995)], [Jpn. J.
      Appl. Phys. 45, 7141-7151 (2006)], where a cylindrical symmetry and a different
      lengthscale is present. In photothermal single (nano-)particle microscopy,
      however, a complicated, though prediction-wise limited, electrodynamic scattering
      treatment was established [Phys. Rev. B 73, 045424 (2006)] during the emergence
      of this new technique. Our recent study [ACS Nano, DOI: 10.1021/nn300181h]
      extended this approach into a full ab-initio model and showed for the first time
      that the mechanism behind the signal, despite its nanoscopic origin, is also the
      lens-like action of the induced refractive index profile only hidden in the
      complicated guise of the theoretical generalized Mie-like framework. The
      diffraction model proposed here yields succinct analytical expressions for the
      axial photothermal signal shape and magnitude and its angular distribution, all
      showing the clear lens-signature. It is further demonstrated, that the Gouy-phase
      of a Gaussian beam does not contribute to the relative photothermal signal in
      forward direction, a fact which is not easily evident from the more rigorous EM
      treatment. The presented model may thus be used to estimate the signal shape and
      magnitude in photothermal single particle microscopy.

PMID- 22453478
TI  - Energy-efficient WDM-OFDM-PON employing shared OFDM modulation modules in optical
      line terminal.
AB  - We propose and experimentally demonstrate a scheme to improve the energy
      efficiency of wavelength division multiplexing - orthogonal frequency division
      multiplexing - passive optical networks (WDM-OFDM-PONs). By using an N * M opto
      mechanic switch in optical line terminal (OLT), an OFDM modulation module is
      shared by several channels to deliver data to multiple users with low traffic
      demands during non-peak hours of the day, thus greatly reducing the number of
      operating devices and minimizing the energy consumption of the OLT. An experiment
      utilizing one OFDM modulation module to serve three optical network units (ONUs)
      in a WDM-OFDM-PON is performed to verify the feasibility of our proposal.
      Theoretical analysis and numerical calculation show that the proposed scheme can
      achieve a saving of 23.6% in the energy consumption of the OFDM modulation
      modules compared to conventional WDM-OFDM-PON.

PMID- 22453479
TI  - Calibrating the interaction matrix for the LINC-NIRVANA high layer wavefront
      sensor.
AB  - LINC-NIRVANA is a near-infrared Fizeau interferometric imager that will operate
      at the Large Binocular Telescope. In preparation for the commissioning of this
      instrument, we conducted experiments for calibrating the high-layer wavefront
      sensor of the layer-oriented multi-conjugate adaptive optics system. For
      calibrating the multi-pyramid wavefront sensor, four light sources were used to
      simulate guide stars. Using this setup, we developed the push-pull method for
      calibrating the interaction matrix. The benefits of this method over the
      traditional push-only method are quantified, and also the effects of varying the
      number of push-pull frames over which aberrations are averaged is reported.
      Finally, we discuss a method for measuring mis-conjugation between the deformable
      mirror and the wavefront sensor, and the proper positioning of the wavefront
      sensor detector with respect to the four pupil positions.

PMID- 22453480
TI  - Indium-rich InGaN epitaxial layers grown pseudomorphically on a nano-sculpted
      InGaN template.
AB  - Indium-rich InGaN epitaxial layers with a p-i-n structure were grown
      pseudomorphically on a strain-relaxed InGaN template to reduce structural strain
      induced by lattice mismatch. We applied a nano-sculpting process to improve the
      crystal quality of the strain-relaxed InGaN template. The results show that the
      nano-sculpting process can suppress effectively the threading dislocation
      generation and improves significantly the I-V characteristic of the InGaN p-i-n
      structure. This InGaN template technique with nano-sculpting process shows great
      potential for future applications in indium-rich InGaN optic-electron devices.

PMID- 22453481
TI  - Improving the radiative decay rate for dye molecules with hyperbolic
      metamaterials.
AB  - We directly demonstrate an improvement in the radiative decay rate of dye
      molecules near multilayer hyperbolic metamaterials (HMMs). Our comprehensive
      study shows a radiative decay rate for rhodamine 800 (Rh800) that is several
      times higher due to the use of HMM samples as compared to dielectric substrates.
      This is also the first experimental demonstration that multilayer hyperbolic
      metamaterials provide an increase in the radiative decay rate relative to those
      from either thin or thick gold films.

PMID- 22453482
TI  - Dual-wavelength passive and hybrid mode-locking of 3, 4.5 and 10 GHz
      InAs/InP(100) quantum dot lasers.
AB  - We present an investigation of passive and hybrid mode-locking in Fabry-Perot
      type two-section InAs/InP(100) quantum dot lasers that show dual wavelength
      operation. Over the whole current and voltage range for mode-locking of these
      lasers, the optical output spectra show two distinct lobes. The two lobes provide
      a coherent bandwidth and are verified to lead to two synchronized optical pulses.
      The generated optical pulses are elongated in time due to a chirp which shows
      opposite signs over the two spectral lobes. Self-induced mode-locking in the
      single-section laser shows that the dual-wavelength spectra correspond to
      emission from ground state. In the hybrid mode-locking regime, a map of locking
      range is presented by measuring the values of timing jitter for several values of
      power and frequency of the external electrical modulating signal. An overview of
      the systematic behavior of InAs/InP(100) quantum dot mode-locked lasers is
      presented as conclusion.

PMID- 22453483
TI  - Antireflective coatings for multijunction solar cells under wide-angle ray
      bundles.
AB  - Two important aspects must be considered when optimizing antireflection coatings
      (ARCs) for multijunction solar cells to be used in concentrators: the angular
      light distribution over the cell created by the particular concentration system
      and the wide spectral bandwidth the solar cell is sensitive to. In this article,
      a numerical optimization procedure and its results are presented. The potential
      efficiency enhancement by means of ARC optimization is calculated for several
      concentrating PV systems. In addition, two methods for ARCs direct
      characterization are presented. The results of these show that real ARCs slightly
      underperform theoretical predictions.

PMID- 22453484
TI  - Integrated liquid-core optical fibers for ultra-efficient nonlinear liquid
      photonics.
AB  - We have developed a novel integrated platform for liquid photonics based on
      liquid core optical fiber (LCOF). The platform is created by fusion splicing
      liquid core optical fiber to standard single-mode optical fiber making it fully
      integrated and practical - a major challenge that has greatly hindered progress
      in liquid-photonic applications. As an example, we report here the realization of
      ultralow threshold Raman generation using an integrated CS2 filled LCOF pumped
      with sub-nanosecond pulses at 532 nm and 1064 nm. The measured energy threshold
      for the Stokes generation is 1nJ, about three orders of magnitude lower than
      previously reported values in the literature for hydrogen gas, a popular Raman
      medium. The integrated LCOF platform opens up new possibilities for ultralow
      power nonlinear optics such as efficient white light generation for displays, mid
      IR generation, slow light generation, parametric amplification, all-optical
      switching and wavelength conversion using liquids that have orders of magnitude
      larger optical nonlinearities compared with silica glass.

PMID- 22453485
TI  - Influence of polarization state, baud rate and PMD on non-linear impairments in
      WDM systems with mixed PM (D)QPSK and OOK channels.
AB  - In this paper we numerically investigate nonlinear impairments in a WDM system
      with mixed PM (D)QPSK and OOK channels. First we analyze the dependence of XPM
      and XPolM on SOP and baud rate in absence of PMD. In this case we find that the
      nonlinear impairments are highly dependent on relative SOP between the PM (D)QPSK
      and neighbouring OOK channels. The dependence on relative SOP is more pronounced
      in differential detection than in coherent detection. However, with increasing
      values of PMD this dependence decreases, and non-linear tolerance improves.

PMID- 22453486
TI  - Fast source optimization involving quadratic line-contour objectives for the
      resist image.
AB  - In Abbe's formulation, source optimization (SO) is often formulated into a linear
      or quadratic problem, depending on the choice of objective functions. However,
      the conventional approach for the resist image, involving a sigmoid
      transformation of the aerial image, results in an objective with a functional
      form. The applicability of the resist-image objective to SO or simultaneous
      source and mask optimization (SMO) is therefore limited. In this paper, we
      present a linear combination of two quadratic line-contour objectives to
      approximate the resist image effect for fast convergence. The line-contour
      objectives are based on the aerial image on drawn edges using a constant
      threshold resist model and that of pixels associated with an intensity minimum
      for side-lobe suppression. A conjugate gradient method is employed to assure the
      convergence to the global minimum within the number of iterations less than that
      of source variables. We further compare the optimized illumination with the
      proposed line-contour objectives to that with a sigmoid resist-image using a
      steepest decent method. The results show a 100x speedup with comparable image
      fidelity and a slightly improved process window for the two cases studied.

PMID- 22453487
TI  - Light harvesting improvement of organic solar cells with self-enhanced active
      layer designs.
AB  - We present designs of organic solar cells (OSCs) incorporating periodically
      arranged gradient type active layer. The designs can enhance light harvesting
      with patterned organic materials themselves (i.e. self-enhanced active layer
      design) to avoid degrading electrical performances of OSCs in contrast to
      introducing inorganic concentrators into OSC active layers such as silicon and
      metallic nanostructures. Geometry of the OSC is fully optimized by rigorously
      solving Maxwell's equations with fast and efficient scattering matrix method.
      Optical absorption is accessed by a volume integral of the active layer excluding
      the metallic absorption. Our numerical results show that the OSC with a self
      enhanced active layer, compared with the conventional planar active layer
      configuration, has broadband and wide-angle range absorption enhancement due to
      better geometric impedance matching and prolonged optical path. This work
      provides a theoretical foundation and engineering reference for high performance
      OSC designs.

PMID- 22453488
TI  - Method for estimating the axial intensity derivative in the TIE with higher order
      intensity derivatives and noise suppression.
AB  - It is an effective scheme to the phase retrieval for axial intensity derivative
      computing. In this paper, we demonstrate a method for estimating the axial
      intensity derivative and improving the calculation accuracy in the transport of
      intensity equation (TIE) from multiple intensity measurements. The method takes
      both the higher-order intensity derivatives and the noise into account, and
      minimizes the impact of detecting noise. The simulation results demonstrate that
      the proposed method can effectively reduce the error of intensity derivative
      computing.

PMID- 22453489
TI  - Transmission-grating-photomasked transient spin grating and its application to
      measurement of electron-spin ambipolar diffusion in (110) GaAs quantum wells.
AB  - A circular dichromatic transient absorption difference spectroscopy of
      transmission-grating-photomasked transient spin grating is developed and
      formularized. It is very simple in experimental setup and operation, and has high
      detection sensitivity. It is applied to measure spin diffusion dynamics and
      excited electron density dependence of spin ambipolar diffusion coefficient in
      (110) GaAs quantum wells. It is found that the spin ambipolar diffusion
      coefficient of (110) and (001) GaAs quantum wells is close to each other, but has
      an opposite dependence tendency on excited electron density. This spectroscopy is
      expected to have extensive applicability in the measurement of spin transport.

PMID- 22453490
TI  - Lossless compression of hyperspectral images using hybrid context prediction.
AB  - In this letter a new algorithm for lossless compression of hyperspectral images
      using hybrid context prediction is proposed. Lossless compression algorithms are
      typically divided into two stages, a decorrelation stage and a coding stage. The
      decorrelation stage supports both intraband and interband predictions. The
      intraband (spatial) prediction uses the median prediction model, since the median
      predictor is fast and efficient. The interband prediction uses hybrid context
      prediction. The hybrid context prediction is the combination of a linear
      prediction (LP) and a context prediction. Finally, the residual image of hybrid
      context prediction is coded by the arithmetic coding. We compare the proposed
      lossless compression algorithm with some of the existing algorithms for
      hyperspectral images such as 3D-CALIC, M-CALIC, LUT, LAIS-LUT, LUT-NN, DPCM (C
      DPCM), JPEG-LS. The performance of the proposed lossless compression algorithm is
      evaluated. Simulation results show that our algorithm achieves high compression
      ratios with low complexity and computational cost.

PMID- 22453491
TI  - Transformation thermodynamics: cloaking and concentrating heat flux.
AB  - We adapt tools of transformation optics, governed by a (elliptic) wave equation,
      to thermodynamics, governed by the (parabolic) heat equation. We apply this new
      concept to an invibility cloak in order to thermally protect a region (a dead
      core) and to a concentrator to focus heat flux in a small region. We finally
      propose a multilayered cloak consisting of 20 homogeneous concentric layers with
      a piecewise constant isotropic diffusivity working over a finite time interval
      (homogenization approach).

PMID- 22453492
TI  - Microsurgical anatomy of the optic radiation and related fibers in 3-dimensional
      images.
AB  - BACKGROUND: The fiber dissection technique provides unique 3-dimensional anatomic
      knowledge of the white matter. OBJECTIVE: To examine the optic radiation anatomy
      and its important relationship with the temporal stem and to discuss its findings
      in relation to the approaches to temporal lobe lesions. METHODS: We studied 40
      cerebral hemispheres of 20 brains that had been fixed in formalin solution for 40
      days. After removal of the arachnoid membrane, the hemispheres were frozen, and
      the Klingler technique was used for dissection under magnification. Stereoscopic
      3-dimensional images of the dissection were obtained for illustration. RESULTS:
      The optic radiations are located deep within the superior and middle temporal
      gyri, always above the inferior temporal sulcus. The mean distance between the
      cortical surface and the lateral edge of the optic radiation was 21 mm. Its
      fibers are divided into 3 bundles after their origin. The mean distance between
      the anterior tip of the temporal horn and the Meyer loop was 4.5 mm, between the
      temporal pole and the anterior border of the Meyer loop was 28.4 mm, and between
      the limen insulae and the Meyer loop was 10.7 mm. The mean distance between the
      lateral geniculate body and the lateral margin of the central bundle of the optic
      radiation was 17.4 mm. CONCLUSION: The white matter fiber dissection reveals the
      tridimensional intrinsic architecture of the brain, and its knowledge regarding
      the temporal lobe is particularly important for the neurosurgeon, mostly because
      of the complexity of the optic radiation and related fibers.

PMID- 22453493
TI  - Acute effect of essential oil of Eugenia caryophyllata on cognition and pain in
      mice.
AB  - The essential oil of Eugenia caryophyllata (clove oil; Family: Myrtaceae) is used
      in dental care as an antiseptic and analgesic. The study aims to evaluate the
      effect of clove oil on experimental models of pain and cognition in mice. To
      observe the acute effects of clove oil at different doses, the elevated plus maze
      was used for the assessment of cognition, and the tail flick and formalin tests
      were used for the study of pain. The formalin test showed that clove oil (0.1
      ml/kg, i.p.) demonstrated significantly reduced pain response in both the phases.
      The lower doses (0.025 and 0.05 ml/kg, i.p.) reduced the formalin-induced pain
      response significantly in the second phase only. The tail-flick test showed
      variable response. The dose 0.1 ml/kg, clove oil, significantly decreased the
      tail-flick latency at 30 min and this effect was reversed by naloxone (1 mg/kg).
      On the contrary, the dose 0.025 ml/kg of clove oil, at 30 and 60 min increased
      the mean tail-flick latency compared to control group, but this effect was not
      statistically significant. Yet naloxone significantly (p < 0.05) reversed the
      effect of clove oil 0.025 ml/kg at 30 min. Clove oil (0.025 and 0.05 ml/kg, i.p.)
      significantly reversed the scopolamine-induced retention memory deficit induced
      by scopolamine, but clove oil (0.1 ml/kg, i.p.) significantly reversed both
      acquisition as well as retention deficits in elevated plus maze induced by the
      scopolamine. Clove oil exhibits reduced pain response by a predominantly
      peripheral action as evidenced by formalin test and the tail flick test showed
      the involvement of opioid receptors. Clove oil also significantly improved
      scopolamine-induced retention memory deficit at all doses.

PMID- 22453494
TI  - Depression as unhomelike being-in-the-world? Phenomenology's challenge to our
      understanding of illness.
AB  - Fredrik Svenaeus has applied Heidegger's concept of 'being-in-the-world' to
      health and illness. Health, Svenaeus contends, is a state of 'homelike being-in
      the-world' characterised by being 'balanced' and 'in-tune' with the world.
      Illness, on the other hand, is a state of 'unhomelike being-in-the-world'
      characterised by being 'off-balance' and alienated from our own bodies. This
      paper applies the phenomenological concepts presented by Svenaeus to cases from a
      study of depression. In doing so, we show that while they can certainly enrich
      our understanding of depression, they can also reveal a clash between some
      societal definitions of illness and the individual's definition. Phenomenological
      analysis may thus cause us to question what we mean, or think should be meant, by
      the terms 'health' and 'illness'.

PMID- 22453495
TI  - Esophageal motility after laparoscopic Roux-en-Y gastric bypass: the manometry
      should be preoperative examination routine?
AB  - BACKGROUND: Our goal was to identify the changes of esophageal motility, lower
      esophageal sphincter (LES) function, and eating adaptation before and after Roux
      en-Y gastric bypass (RYGBP) and whether manometry should be a routine examination
      in patients who undergo this procedure. METHODS: A total of 81 patients underwent
      manometry before surgery and 1 year after surgery. The control group consisted of
      10 nonobese volunteers. Patients were classified as presenting with vomiting and
      without vomiting 1 year after surgery. Manometric variables were compared before
      and after surgery. Statistical analysis was performed using Wilcoxon and Mann
      Whitney test. RESULTS: The patients (45.6%) had preoperative manometric findings,
      29.8% had LES hypertonia, 18.9% LES hypotonia, 43.2% increase in wave amplitude
      of contraction, and three 8.1% abnormal peristalsis. One year after surgery
      manometry was abnormal in 62.9% of patients, 11.7% with hypertonia and 15.7% with
      hypotonia of the LES, 53% with changes in amplitude contraction and 19.6% with
      abnormal peristalsis. The control group showed no manometric abnormalities.
      Chronic vomiting was noted in 21% of patients. When comparing all variables
      between the pre and postoperative periods, there was no significant difference
      for all of them except for peristalsis. Comparing the results of manometric
      findings between the vomiting and non-vomiting groups, no significant changes
      were found in the variables studied. CONCLUSIONS: There was an association
      between RYGBP and motor abnormalities in the esophagus but no differences in
      postoperative feeding adaptation. Thus, we conclude that esophageal manometry is
      not necessary as a routine preoperative examination.

PMID- 22453497
TI  - Abstracts of the 38th Annual Meeting of the Society of Gynecologic Surgeons
      (SGS), 2012, Baltimore, Maryland.

PMID- 22453496
TI  - The relationship between volume and outcome after bariatric surgery: a nationwide
      study in Taiwan.
AB  - BACKGROUND: This study purposed to explore the impact of hospital volume and
      surgeon volume on hospital resource utilization after bariatric surgery and to
      identify the predictors of length of stay (LOS) and hospital treatment cost in a
      nationwide population in Taiwan. METHODS: This population-based cohort study
      retrospectively analyzed 2,674 bariatric surgery procedures performed from 1997
      to 2008. Hospitals were classified as low- and high-volume hospitals if their
      annual number of bariatric surgeries were <35 and >= 35, respectively. Surgeons
      were classified as low- and high-volume surgeons if their annual number of
      bariatric surgeries were <15 and >= 15, respectively. Hierarchical linear
      regression models were used to predict LOS and hospital treatment cost. RESULTS:
      The mean LOS was 7.67 days and the LOS for high-volume hospitals/surgeons was, on
      average, 28%/31% shorter than that for low-volume hospitals/surgeons. The mean
      hospital treatment cost was US$2,344.08, and the average hospital costs for high
      volume hospitals/surgeons were 10%/13% lower than those for low-volume
      hospitals/surgeons. Advanced age, male gender, high Charlson co-morbidity index,
      and current treatment in a low-volume hospital, by a low-volume surgeon, and via
      open gastric bypass were significantly associated with long LOS and high hospital
      treatment cost (P < 0.001). CONCLUSIONS: The data suggest that annual surgical
      volume is the key factor in hospital resource utilization. The results improve
      the understanding of medical resource allocation for this surgical procedure and
      can help to formulate public health policies for optimizing hospital resource
      utilization for related diseases.

PMID- 22453498
TI  - Nosema ceranae an emergent pathogen of Apis mellifera in Chile.
AB  - The microsporidian Nosema apis and Nosema ceranae have been associated with
      colony disorders of Apis mellifera and Apis cerana, respectively. N. apis is
      endemic in South America. Recently, N. ceranae has been detected in Brazil,
      Uruguay and Argentina. No report of its presence, distribution and prevalence in
      Chile is available. Here, we present a real-time PCR-based method that was able
      to discriminate between N. apis and N. ceranae. The dynamic range of this assay
      was 100 to 100,000 spores per honeybee. False-negative results were avoided due
      to the use of ACTIN gene as internal standard. False-positive results were
      obtained neither in experimentally nor in naturally contaminated samples. Using
      this method, we screened 240 beehives from the Chilean region where 42% of the
      total country honey production take places (Region del Biobio). Nosema spp. were
      detected in the four provinces and in 20 of the 26 communes of the region. Among
      the samples analysed, 49% were positive for N. ceranae. Their infection level
      ranged from 200 to more than 100,000 spores per honeybee. N. apis was not
      detected in this region. Hence, our data show that in Chile N. ceranae is an
      emergent pathogen that is been replacing N. apis. Also, they support that N.
      ceranae maybe the actual responsible for nosemosis in A. mellifera in South
      America.

PMID- 22453499
TI  - Gastrointestinal parasites in Chinstrap Penguins from Deception Island, South
      Shetlands, Antarctica.
AB  - Knowledge about parasites of Antarctic birds is fragmented and scarce. The aim of
      this work is to contribute to the knowledge of gastrointestinal parasites of the
      Chinstrap Penguin (Pygoscelis antarctica) from Deception Island (South Shetlands,
      Antarctica). Gastrointestinal tracts of 64 fresh dead individuals (61 chicks and
      three adults) were collected from December 2006 to February 2009 and examined for
      macroparasites. Three adult parasite species were found: two Cestoda species
      (Parorchites zederi and Tetrabothrius pauliani) and one Nematoda species
      (Stegophorus macronectes). Also, immature acanthocephalans (Corynosoma sp.) were
      found in one penguin. The low parasite richness observed could be related to the
      stenophagic and pelagic diet of the host species. False negatives were found in
      coprological studies.

PMID- 22453500
TI  - Purification and cellular localization of the Entamoeba histolytica
      transcarboxylase.
AB  - Genome analysis of Entamoeba histolytica predicts the presence of acetyl-CoA
      carboxylase. Using Western blot, histochemistry, and confocal microscopy, we
      demonstrated the presence of a biotin-containing protein in the cytoplasm of E.
      histolytica, with a molecular weight of 136 kDa and biotin-carboxylase activity.
      This protein probably corresponds to a transcarboxylase that catalyzes the rate
      limiting reaction leading to fatty acid elongation.

PMID- 22453502
TI  - What is female pelvic medicine and reconstructive surgery?

PMID- 22453501
TI  - Corrin ring-induced redox tuning.
AB  - The density functional calculations suggest that the expansion of the corrin
      macrocycle's N(4) core by 0.06-0.10 A leads to an appreciable lowering of 100-150
      mV vs. saturated calomel electrode in the reduction potentials of two
      biologically important B(12) cofactors namely methylcobalamin and
      adenosylcobalamin respectively. This redox tuning of B(12) cofactors may
      encourage the electron transfer-based activation mechanism for B(12)-dependent
      enzymes.

PMID- 22453503
TI  - Pelvic support and urinary function improve in women after surgically induced
      weight reduction.
AB  - OBJECTIVE: : The objective of this study was to assess pelvic organ support and
      symptoms in morbidly obese women before and after weight reductive surgery.
      METHODS: : Fifty-four women were enrolled in this institutional review board
      approved protocol. Data collection at baseline and 6 months following surgery
      included a Pelvic Organ Prolapse Quantification examination, questionnaires
      including the Pelvic Floor Distress Inventory, the Pelvic Floor Impact
      Questionnaire, and the Pelvic Organ Prolapse-Urinary Incontinence Sexual Function
      Questionnaire short form, and a 3-day voiding diary. Before-surgery and after
      surgery measures were compared using paired Student t tests for continuous,
      normally distributed data or the Wilcoxon signed rank test for ordinal data.
      RESULTS: : Baseline and 6-month data were available for 34 women. The mean body
      mass index was 46 +/- 6 kg/m at baseline and 33 +/- 6 kg/m after 6 months.
      Subjects with >=stage 2 prolapse at baseline demonstrated an improvement of 0.5
      cm (baseline, 0.9 +/- 0.8 cm; after 6 months, -1.4 +/- 0.9 cm) in the anterior
      vaginal compartment (points Aa/Ba) 6 months following weight reductive surgery (P
      = 0.05). Of 24 women who completed 3-day voiding diaries, 12 were incontinent at
      baseline with a median number of incontinent episodes of 6.5 per day (range, 3
      34). After surgery, 6 incontinent women became continent. In the 6 women who
      remained incontinent after surgery, the number of incontinent episodes per day
      decreased by a median of 2.5 (range, 1-11). Pelvic Floor Distress Inventory
      scores improved following weight reduction (baseline, 115 +/- 80; after 6 months,
      58 +/- 70; P < 0.01). DISCUSSION: : Obese women, after surgically induced weight
      loss, demonstrate an improvement in anterior vaginal support, urinary leakage and
      pelvic floor symptoms.

PMID- 22453504
TI  - Residents as teachers of the pelvic floor and perineal anatomy.
AB  - CONTEXT: : As much as 50% of teaching is conducted by residents with limited
      clinical experience, pedagogical acumen or knowledge of the subject they teach.
      OBJECTIVE: : The purpose was to develop a residents-as-teachers program that
      integrated a basic science curriculum of the pelvic floor and perineal anatomy
      with clinical correlations while instructing residents in certain clinical and
      pedagogical skills. DESIGN: : A resident-as-teacher curriculum that focused on
      both the pedagogy and content related to pelvic floor and perineal anatomy was
      designed and collaboratively implemented by an anatomist, obstetrics/gynecology
      clinicians and a professional educator. It was implemented 4 times, with each
      session offered as a 3-hour training. A mixed-methods research design was used to
      study the impact of the resident-as-teacher program on the residents. SETTING: :
      A medical school anatomy laboratory. PATIENTS OR PARTICIPANTS: : A total of 51
      residents in the Brigham and Women's Hospital/Massachusetts General Hospital
      Integrated Residency Training Program in Obstetrics and Gynecology (PG-1, -2, -3
      and -4) and 4 Harvard Medical School students. INTERVENTIONS: : Four 3-hour
      resident-as-teacher curricular sessions. MAIN OUTCOME MEASURES: : To understand
      the impact of an innovative resident-as-teacher curriculum on Obstetrics and
      Gynecology residents. RESULTS: : The intervention significantly affected the
      residents' knowledge of pelvic floor and perineal anatomy and significantly
      increased the residents' comfort level with teaching pelvic floor and perineal
      anatomy. All the residents agreed that learning how to teach using clinical
      correlations and integrating the laboratory experience were excellent and that it
      was beneficial to be taught by the combination of clinical, anatomical and
      educational faculty. CONCLUSIONS: : Teaching residents how to teach using a hands
      on anatomical laboratory experience relevant to their daily work was
      overwhelmingly positive. The recommendation was to continue the program and
      implement the session at least biannually.

PMID- 22453505
TI  - Vaginal hysterectomy at the time of transvaginal mesh placement.
AB  - INTRODUCTION: : Previous investigations have shown an increased risk of mesh
      erosion when concomitant vaginal hysterectomy is performed at the time of
      transvaginal reconstruction with mesh. We hypothesize that vaginal hysterectomy
      can be performed without a high risk of erosion. METHODS: : This is a
      retrospective, repeated-measures study of women with uterovaginal prolapse who
      underwent vaginal hysterectomy and pelvic reconstruction with a transvaginal mesh
      technique using the Prolift system. Mesh was never placed behind the cuff closure
      and "T" incisions were not used. We compared preoperative quality-of-life and
      Pelvic Organ Prolapse Quantification values to postoperative values. RESULTS: :
      Forty women met the study criteria. The median length of follow-up was 12 months
      (range 4-43 months). Thirty-two (80%) of the women had at least 1 year of follow
      up. Significant improvements were found in all quality-of-life measures. Except
      for genital hiatus and perineal body length, a significant change was seen in all
      Pelvic Organ Prolapse Quantification measures. The greatest mean change found was
      for point "C" going from +2.4 to -6.8 cm (P < 0.001). There was 1 (2.5%) mesh
      erosion. CONCLUSIONS: : When incisions for mesh placement are kept separate from
      the vaginal cuff, transvaginal mesh reconstruction can be safely performed at the
      time of hysterectomy.

PMID- 22453506
TI  - Urinary incontinence, fecal incontinence and pelvic organ prolapse in a
      population-based, racially diverse cohort: prevalence and risk factors.
AB  - OBJECTIVES: : We investigated the prevalence of and risk factors for combinations
      of urinary incontinence (UI), fecal incontinence (FI) and pelvic organ prolapse
      (POP) in racially diverse women older than 40 years. METHODS: : The Reproductive
      Risks for Incontinence Study at Kaiser is a population-based study with data from
      2106 women older than 40 years. Pelvic floor conditions were determined by self
      report. Risk factors were assessed by self-report, interview and record review.
      Independent risk factors were identified by multinomial logistic regression
      analysis. RESULTS: : At least one pelvic floor condition was reported by 714
      (34%) women. Of these, 494 (69%) had only UI, 60 (8%) only POP, and 46 (6%) only
      FI. Both UI and FI were reported by 64 (9%) and both UI and POP by 51 (7%). Among
      women with FI, 60% reported more than one condition. Corresponding figures for
      POP and UI were 49% and 18%. Estrogen use and constipation were shared risk
      factors for UI, FI and POP. Body mass index was a unique risk factor UI only,
      diabetes FI only and parity POP only. No clear pattern could be found to support
      the hypothesis that risk factors for single conditions are more strongly
      associated with combined conditions. CONCLUSIONS: : Patients with FI or POP often
      have concomitant UI. These diseases both share and have unique risk factors in a
      complex pattern.

PMID- 22453507
TI  - Age as a risk factor for perioperative complications in women undergoing pelvic
      reconstructive surgery.
AB  - OBJECTIVE: : The purpose of this study is to determine whether the age of a
      patient undergoing pelvic reconstructive and/or anti-incontinence pelvic surgery
      is a risk factor for perioperative complications. STUDY DESIGN: : A retrospective
      chart review was conducted of women who underwent pelvic reconstructive and anti
      incontinence pelvic surgery between the years 2000 and 2006. The women underwent
      surgery by 1 urogynecologist, at 2 city hospitals. Patients with incomplete
      medical documentation were excluded from the study. The variables investigated
      included demographics, smoking history, prior surgical history, comorbidities,
      length of surgery, estimated blood loss, deep venous thrombosis prophylaxis,
      perioperative antibiotics, type of anesthesia, and the American Society of
      Anesthesia classification. The outcome variables included change in hematocrit,
      length of hospitalization, intraoperative injury, and prevalent postoperative
      complications. Postoperative complications included, febrile morbidity (T >= 101,
      >=24 hours following surgery), documented infection (acute cystitis, wound or
      pelvic infection, and pneumonia), cardiovascular compromise (myocardial
      infarction, cerebral vascular accident, congestive heart failure, hypotension,
      arrhythmia), renal failure, graft erosion, dyspareunia, urinary retention, anemia
      (hematocrit <=24%), ileus, hematoma, seroma, and ICU admission. A point system
      was created for each complication to limit the variation in data collection.
      Morbidity and mortality were determined for women aged <=55 years old (group I),
      56 to 69 years old (group II), and >=70 years old (group III). One-way analysis
      of variance was used to determine whether a difference exist between the age
      groups, and exact chi tests were used to identify the association between age and
      the aforementioned outcome variables. An alpha level of 0.05 was predetermined as
      the level of statistical significance. RESULTS: : A total of 411 patients
      underwent pelvic reconstructive surgery, 404 surgical procedures met the
      inclusion criteria, group I (n = 168), group II (n = 152), and group III (n =
      84). Most surgeries were done vaginally. The women were followed up for an
      average of 185 days (group I), 243 days (group II), and 248 days (group III).
      There was no significant difference in the operative time, length of
      hospitalization, or follow-up period between the groups. Demographically, the
      groups had a similar composition. There are minor differences in prior medical
      and surgical histories between the age groups. Older women were more likely to
      have a history of cardiovascular disease. Patients in group II were more likely
      to have a prior history of a midurethral sling (P = 0.02). Patients in group III,
      were more likely to have a prior history of an abdominal hysterectomy (P = 0.01)
      and anterior colporrhaphy with graft (P = 0.01). In this study, group II
      underwent more salpingectomies (P = 0.01) and group III underwent more
      hysterectomies (P = 0.01), oophorectomies (P = 0.05), and posterior
      colporrhaphies (P = 0.001). Overall, the rate of intraoperative complications was
      1.0%. There was no statistical difference in the postoperative complication rate
      among the 3 age groups (P = 0.27) and no fatalities. CONCLUSION: : The age of a
      patient undergoing vaginal reconstructive and/or anti-incontinence pelvic surgery
      does not appear to be a risk factor for perioperative complications.

PMID- 22453508
TI  - Normative data for commonly used validated pelvic floor disorder questionnaires
      in women.
AB  - OBJECTIVE: : To report measures of central tendency for Pelvic Floor Distress
      Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), and 12-item short
      form Pelvic Organ Prolapse-Incontinence-Sexual Function Questionnaire (PISQ-12)
      in women with POPQ stage <=I. METHODS: : An analysis was conducted of 67 women
      participating as controls in a body image in prolapse study who were recruited
      from a general gynecology setting. Following are the inclusion criteria: (1)
      presenting complaint was not prolapse/incontinence symptoms; (2) answered "no" to
      questions, (a) "Do you usually have a sensation of bulging protrusion from the
      vaginal area?" and (b) "Do you usually have a bulge or something falling out that
      you can see or feel in the vaginal area?" (3) POPQ stage <=I; and (4) no prior
      surgery for prolapse/incontinence. Descriptive statistics were calculated for
      PISQ-12 and long and short forms of PFDI and PFIQ. RESULTS: : Subjects had a mean
      age of 54 +/- 8 years and a median of POPQ stage I. Median total and subscale
      scores for long and short forms of PFDI and PFIQ were <=15. Mean PISQ-12 was 34
      +/- 3. Reliability testing using Cronbach's alpha was performed: PFDI (alpha =
      0.930), PFIQ (alpha = 0.978), and PISQ-12 (alpha = 0.469). CONCLUSIONS: :
      Knowledge of normative data for pelvic floor symptom questionnaires is important
      to better assess outcomes after reconstructive surgery for pelvic floor
      disorders.

PMID- 22453509
TI  - Now or later...Does timing of a midurethral sling in relation to transvaginal
      prolapse repair affect continence outcomes at 1 year?
AB  - OBJECTIVE: : To determine if timing of a midurethral sling (MUS) relative to
      prolapse repair affects continence. METHODS: : Continence outcomes were compared
      in women with stress urinary incontinence (SUI) undergoing prolapse repair with
      Prolift. Groups included concomitant procedure (CP) and planned staged procedure
      (PSP). Continence was assessed by validated questionnaires and satisfaction by
      visual analog scale (0-10). RESULTS: : Twenty women underwent CP and 29 underwent
      PSP. One year after prolapse repair, 66% in the PSP group did not pursue MUS.
      Still, there were no significant differences at 1 year between groups in
      subjective SUI (CP = 22.2%, PSP = 21.4%), change in the severity of SUI (Urinary
      Distress Inventory: DeltaPSP = -56.1, DeltaCP = -59.7; Urinary Impact
      Questionnaire: DeltaPSP = -47.1, DeltaCP = -48) or satisfaction (CP = 8.8, PSP =
      9.2). CONCLUSIONS: : A staged approach for treatment of SUI after prolapse repair
      appears to result in comparable continence and satisfaction outcomes to
      concomitant MUS placement 1 year after prolapse surgery despite 2/3 of women not
      pursuing MUS. Appropriately powered trials are warranted to confirm the potential
      benefits of a decreased need for incontinence surgery with a planned staged
      approach.

PMID- 22453510
TI  - Gynecologic problems following abdominoperineal resection of the anus and rectum 
      the post-miles syndrome.
AB  - BACKGROUND: : Abdominoperineal resection is a surgical technique used to treat a
      variety of colorectal diseases. Although there are several published studies
      describing long-term pelvic floor functioning in women who have undergone this
      procedure, little is known specifically about gynecologic problems that may
      develop after surgery. CASES: : We describe a series of 3 patients all presenting
      with similar gynecologic complaints status-post abdominoperineal resection,
      including copious vaginal discharge, dyspareunia, and difficulty on the part of
      their health care providers in seeing the cervix during speculum examinations.
      The presenting syndrome is felt to be due to a reduction in vaginal caliber and
      steep angulation of the upper vagina due to the plication of the levator ani
      during the typical closure of the pelvic floor at the completion of surgery.
      Successful therapy has been achieved with conservative measures as well as
      surgical treatment. CONCLUSIONS: : Abdominoperineal resection may result in a
      syndrome of gynecologic complaints. Medical and/or surgical therapies are
      effective in controlling symptoms.

PMID- 22453511
TI  - Sling plication for recurrent stress urinary incontinence.
AB  - OBJECTIVES: : Management of recurrent stress urinary incontinence (SUI) after
      synthetic mid-urethral sling placement is a challenging clinical dilemma. This
      case series describes a safe, minimally invasive treatment option for recurrent
      SUI after failure of the primary mid-urethral sling procedure. METHODS: : Twenty
      women with recurrent SUI after previous synthetic mid-urethral sling placement
      underwent plication of the sling with 2-0 polyester suture under intravenous
      sedation with an intra-operative cough stress test between December 2004 and
      December 2008. A retrospective chart review was performed to obtain pertinent
      preoperative and postoperative data. RESULTS: : Nine of the patients had prior
      retropubic synthetic mid-urethral slings. The other 11 women had transobturator
      mid-urethral slings, 10 of whom had slings via the outside-in approach and 1 had
      a single-incision mini-sling placed. The mean patient age was 59.8 years (range
      38-83 years). Sling plication was performed at a median of 159.5 days after
      initial sling placement (range 26-2090 days). Overall 85% of patients had
      subjective improvement in SUI after sling plication with a median follow-up of
      54.5 days (range 29-972 days). Those patients with prior retropubic slings had a
      100% improvement rate compared to 72% improvement with prior obturator slings (P
      = 0.22). The subjective cure rate was 65%, 88% for the retropubic slings and 45%
      for the transobturator slings (P = 0.07). There were no complications.
      CONCLUSIONS: : Midline plication of previously placed synthetic mid-urethral
      slings is a safe and effective method of treating recurrent SUI.

PMID- 22453512
TI  - Chironomid mouthpart deformities as indicator of environmental quality: a case
      study in Lake Trasimeno (Italy).
AB  - The aim of the present study was to monitor mouthpart deformities of Chironomus
      plumosus (Insecta-Diptera) in Lake Trasimeno (2000-2010) in relation with
      sediment contamination by heavy metals, which is one of the main causes of
      deformity induction. In Lake Trasimeno, concentrations of heavy metals in the
      investigated littoral zone were low, in comparison with those of the central
      area. By contrast, the incidence of deformities was much higher in the littoral
      station (2006-2009) than in the central area. In the littoral zone, the
      deformities progressively decreased and by 2010 reached values similar to those
      observed in the central area (2000-2002, 2010). This decrease was mainly due to
      the reduction of severe deformities, thus indicating an environmental quality
      recovery of this littoral sector. Chemical analysis revealed that the higher
      incidence of deformities in the littoral zone was not caused by heavy metal
      contamination, unless they may have contributed to a joint action with other
      toxicants. The present study on Lake Trasimeno provided additional evidence that
      chironomid mouthpart deformities can be used in biomonitoring programs to
      evaluate sediment contamination by toxicants. Since mouthpart deformities may
      also be induced by compounds not included in routine chemical analyses, they may
      better reflect sediment quality than chemical analysis alone.

PMID- 22453513
TI  - No island hopping for Hawaiian petrels.

PMID- 22453514
TI  - Cardiac surgical experience in northern Nigeria.
AB  - A pilot study was undertaken to determine the feasibility of establishing a heart
      surgery programme in northern Nigeria. During three medical missions by a
      visiting US team, in partnership with local physicians, 18 patients with heart
      diseases underwent surgery at two referral hospitals in the region. Sixteen
      (88.9%) patients underwent the planned operative procedure with an observed 30
      day mortality of 12.5% (2/16) and 0% morbidity. Late complications were
      anticoagulant related in mechanical heart valve patients and included a first
      trimester abortion one year  postoperatively, and a death at two years from
      haemorrhage during pregnancy. This has prompted us to now consider bioprosthetics
      as the valve of choice in women of childbearing age in this patient population.
      This preliminary result has further stimulated the interest of all stakeholders
      on the urgency to establish open-heart surgery as part of the armamentarium to
      combat the ravages of heart diseases in northern Nigeria.

PMID- 22453515
TI  - Dental and oral anomalies in incontinentia pigmenti: a systematic review.
AB  - OBJECTIVES: Incontinentia pigmenti (IP) is an X-linked genodermatosis caused by a
      mutation of the IKBKG gene. The objective of this study was to present a
      systematic review of the dental and oral types of anomalies, to determine the
      total number and sex distribution of the anomalies, and to analyze possible
      therapies. MATERIALS AND METHODS: We analyzed the literature data from 1,286 IP
      cases from the period 1993-2010. RESULTS: Dental and/or oral anomalies were
      diagnosed for 54.38% of the investigated IP patients. Most of the anomaly types
      were dental, and the most frequent of these were dental shape anomalies,
      hypodontia, and delayed dentition. The most frequent oral anomaly types were
      cleft palate and high arched palate. IKBKG exon 4-10 deletion was present in
      86.36% of genetically confirmed IP patients. CONCLUSIONS: According to the
      frequency, dental and/or oral anomalies represent the most frequent and important
      IP minor criteria. The most frequent mutation was IKBKG exon 4-10 deletion. The
      majority of dental anomalies and some of the oral anomalies could be corrected.
      CLINICAL RELEVANCE: Because of the presence of cleft palate and high arched
      palate in IP patients, these two anomalies may be considered as diagnostic IP
      minor criteria as well.

PMID- 22453516
TI  - Vampiric isolation of extracellular fluid from Caenorhabditis elegans.
AB  - The genetically tractable model organism C. elegans has provided insights into a
      myriad of biological questions, enabled by its short generation time, ease of
      growth and small size.  This small size, though, has disallowed a number of
      technical approaches found in other model systems.  For example, blood
      transfusions in mammalian systems and grafting techniques in plants enable asking
      questions of circulatory system composition and signaling.  The circulatory
      system of the worm, the pseudocoelom, has until recently been impossible to assay
      directly.  To answer questions of intercellular signaling and circulatory system
      composition C. elegans researchers have traditionally turned to genetic analysis,
      cell/tissue specific rescue, and mosaic analysis.  These techniques provide a
      means to infer what is happening between cells, but are not universally
      applicable in identification and characterization of extracellular molecules. 
      Here we present a newly developed technique to directly assay the pseudocoelomic
      fluid of C. elegans.  The technique begins with either genetic or physical
      manipulation to increase the volume of extracellular fluid.  Afterward the
      animals are subjected to a vampiric reverse microinjection technique using a
      microinjection rig that allows fine balance pressure control.  After isolation of
      extracellular fluid, the collected fluid can be assayed by transfer into other
      animals or by molecular means.  To demonstrate the effectiveness of this
      technique we present a detailed approach to assay a specific example of
      extracellular signaling molecules, long dsRNA during a systemic RNAi response. 
      Although characterization of systemic RNAi is a proof of principle example, we
      see this technique as being adaptable to answer a variety of questions of
      circulatory system composition and signaling.

PMID- 22453517
TI  - Corneal honey bee sting: endoilluminator-assisted removal of retained stinger.
AB  - To report the clinical findings and a novel method of removal of bee sting using
      an endoillumination light source the following methods were used: clinical
      presentation, slit-lamp photographs, serial endothelial images and surgical
      management of a case of retained bee sting in the cornea. The bee sting was
      surgically removed by forceps under focal illumination with an endoillumination
      light source. Topical steroids and cycloplegics were given postoperatively to
      control the inflammation. The patient had complete visual recovery and partial
      resolution of endothelial changes after 1 year of treatment. The clinical picture
      of a corneal honey bee sting resembles keratouveitis. Focal corneal infiltrate
      and associated low-grade uveitis tend to persist if treated with topical steroids
      only. Early recognition and prompt removal of the stinger may help in the early
      resolution of anterior segment inflammation and prevent irreversible damage to
      endothelial cells.

PMID- 22453518
TI  - Thermoactinospora rubra gen. nov., sp. nov., a thermophilic actinomycete isolated
      from Tengchong, Yunnan province, south-west China.
AB  - Two novel Gram-positive, spore-forming, thermophilic actinomycetes, designated as
      strain YIM 77501(T) and YIM 77570, were isolated from a sandy soil sample
      collected at Tengchong National Volcanic Geological Park, Yunnan province, south
      west China. Phylogenetic analysis based on the 16S rRNA gene sequences suggested
      that the two isolates fell within the family Streptosporangiaceae. The strains
      formed extensively branched substrate and aerial mycelia which carried masses of
      long, straight or irregular spore chains composed of warty ornamented spores.
      Cell walls of the two strains contained meso-diaminopimelic acid and glucose,
      galactose, mannose and ribose were detected as whole-cell sugars. The predominant
      menaquinones were MK-9(H(4)) and MK-9(H(6)). The major polar lipids were
      diphosphatidylglycerol, phosphatidylethanolamine, N-acetylglucosamine-containing
      phospholipids and phosphatidylinositol, phosphatidylinositolmannosides. The major
      cellular fatty acids were iso-C(16:0) and 10-methyl C(17:0). The DNA G+C content
      was 74-76 mol%. On the basis of the morphological and chemotaxonomic
      characteristics as well as the phylogenetic analysis, these strains represents a
      novel species of a new genus within the family Streptosporangiaceae, for which
      the name Thermoactinospora rubra gen. nov., sp. nov. is proposed. The type strain
      of T. rubra is YIM 77501(T) (=DSM 45614(T) = CCTCC AA 2011014(T)).

PMID- 22453519
TI  - Oceanibacterium hippocampi gen. nov., sp. nov., isolated from cutaneous mucus of
      wild seahorses (Hippocampus guttulatus).
AB  - A Gram-negative, aerobic, motile and slightly curved rod-shaped bacterium (BFLP
      8(T)) was isolated from cutaneous mucus of wild long-snouted seahorses
      (Hippocampus guttulatus) captured in northwest Spain (Toralla, Galicia). Strain
      BFLP-8(T) grew at 10-35  degrees C and pH 5-9 (optimally at 25  degrees C and pH
      7.0) and with 1-6 % (w/v) NaCl (optimally with 2 % NaCl). The predominant
      respiratory quinone (90 %) was ubiquinone with ten isoprene units (Q-10) and the
      major fatty acids identified were C(18:1) omega7c (54.8 % of the total), C(19:0)
      cyclo omega8c (11.6 %), C(16:0) (9.5 %), C(18:1) 2-OH (7.1 %) and C(16:1)
      omega11c (6.7 %). The G+C content of the DNA was 57.8 mol%. Phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain BFLP-8(T) formed a distinct
      clade within the family Sneathiellaceae but is not specifically associated with
      any species in the family. On the basis of phenotypic, chemotaxonomic and
      phylogenetic data, strain BFLP-8(T) represents a novel species within a new
      genus, for which the name Oceanibacterium hippocampi gen. nov., sp. nov. is
      proposed. The type strain is BFLP-8(T) (=CECT 7691(T) = DSM 23444(T)).

PMID- 22453520
TI  - Electrochemical monitoring of the metabolic activity of mycobacteria in culture.
AB  - Mycobacterial metabolic activity is typically measured using time-consuming
      manual methods based on nutrient consumption, nucleic acid synthesis or reduction
      of tetrazolium salts. In this study, we propose much simpler electrochemical
      methods for continuous monitoring of the metabolic activity of mycobacteria in
      culture. Chronoamperometry and chronopotentiometry were used to detect metabolic
      activity of both slow-growing and fast-growing mycobacteria using a potentiostat
      with 2D-electrochemical cell. Electrochemical measurements were able to detect
      statistically significant differences in the metabolic activity of approximately
      10(7) mycobacteria in different growth conditions, within less than 24 h of
      mycobacterial culture. The metabolic activity of mycobacteria measured by the
      used electrochemical methods correlated well with changes in general respiratory
      conditions within the cells as it was evaluated by different biochemical tests.
      Chronoamperometry and chronopotentiometry allowed measurement of mycobacterial
      metabolic activity without invasive chemical reactions, at minimal bacterial load
      and when metabolic response of mycobacteria occurs quickly. The proposed
      methodology is simple, rapid and cost-effective, and it is expected that both in
      vitro and in vivo metabolic activity of human mycobacterial pathogens as
      Mycobacterium tuberculosis can be measured when the implementation of this method
      to analyze virulent strains is adapted.

PMID- 22453522
TI  - Synthesis of carbon-coated, porous and water-dispersive Fe3O4 nanocapsules and
      their excellent performance for heavy metal removal applications.
AB  - Porous Fe(3)O(4)@C nanocapsules with a diameter of about 120 nm (about 50 nm
      cavity) were synthesized by combining a sacrificial template method with
      solvothermal treatment. The N(2) adsorption-desorption isotherms reveals their
      mesoporous structure and large BET surface area (159.8 m(2) g(-1)). The magnetic
      investigation indicates their superparamagnetic nature and high saturation
      magnetization (55.93 emu g(-1)). The nanocapsules also exhibit negative zeta
      potential (-27.59 mV) and possess carboxyl groups on the outer carbon layer,
      which keeps them highly dispersive in aqueous solution and provides a chelating
      function for metal ions. The heavy metals removal test demonstrates the excellent
      affinity of nanocapsules, the high efficiency for different metals (>90%), 79 mg
      g(-1) adsorption capacity for Pb(2+) and ultrafast removal process (Pb(2+),
      99.57% within 1 minute). Protected by a porous carbon layer, the nanocapsules
      display excellent acidic resistance and adsorption properties even in an acidic
      solution (pH = 3). Moreover, the metal ions can be easily adsorbed and desorbed
      through manipulating the pH value for adsorbent regeneration and heavy metal
      recycling.

PMID- 22453521
TI  - Naringin treatment improves functional recovery by increasing BDNF and VEGF
      expression, inhibiting neuronal apoptosis after spinal cord injury.
AB  - The aim of this study was to determine the therapeutic efficacy of starting
      naringin treatment 1 day after spinal cord injury (SCI) in rat and to investigate
      the underlying mechanism. SCI was induced using the modified weight-drop method
      in Sprague-Dawley rats. The SCI animals were randomly divided into three groups:
      vehicle-treated group; 20 mg/kg naringin-treated group; 40 mg/kg naringin-treated
      group, and additionally with sham group (laminectomy only). Locomotors functional
      recovery was assessed during the 6 weeks post operation period by performing open
      field locomotors tests and inclined-plane tests. At the end of the study, the
      segments of spinal cord encompassing the injury site were removed for
      histopathological analysis. Immunohistochemistry was performed to observe the
      expression of the brain-derived neurotrophic factor (BDNF). The expression of
      vascular endothelial growth factor (VEGF), B-cell CLL/lymphoma-2 (Bcl-2), BCL-2
      associated X protein (Bax) and caspase-3 were detected by Western blot analysis.
      The apoptotic neural cells were assessed using the TUNEL method. The results
      showed that the naringin-treated animals had significantly better locomotor
      function recovery, less myelin loss, and higher expression of BDNF and VEGF. In
      addition, naringin treatment significantly increased in Bcl-2:Bax ratio, reduced
      the enzyme activity of caspase-3 and decreased the number of apoptotic cells
      after SCI. These findings suggest that naringin treatment starting 1 day after
      SCI can significantly improve locomotor recovery, and this neuroprotective effect
      may be related to the upregulation of BDNF and VEGF and the inhibition of neural
      apoptosis. Therefore, naringin may be useful as a promising therapeutic agent for
      SCI.

PMID- 22453523
TI  - Investigation of chondrocyte hypertrophy and cartilage calcification in a full
      depth articular cartilage explants model.
AB  - Articular cartilage deterioration, which includes cartilage degradation and
      chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD).
      Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a
      robust explants model for investigation of hypertrophy should include this zone.
      The aim of this study was to characterize and investigate the hypertrophy
      promoting potential of different endogenous factors on an ex vivo articular
      cartilage model. The full-depth cartilage explants were harvested from bovine
      femoral condyle and cultured for 13 days in different conditions: 10 ng/ml
      oncostatin M + 20 ng/ml TNF-alpha; 100 ng/ml IGF1; 10-100 ng/ml bFGF; 10-100
      ng/ml BMP2; 50 MUg/ml ascorbic acid in combination with 10 mM beta
      glycerophosphate; and 20-100 ng/ml triiodothyronine. The cellular activity and
      morphology, degradation, formation and calcification, and expression level of
      hypertrophic markers were investigated. The hypertrophic factors tested all
      induced cellular activity and marked morphological changes starting at day 4,
      however, not in a synchronized manner. Both cartilage degradation and formation
      were induced by T3 (P < 0.05). Only T3 had a full hypertrophic gene expression
      profile (P < 0.05). We developed and characterized a novel model for
      investigation of chondrocyte hypertrophy. We speculated that this can become an
      important investigatory tool for investigation of matrix turnover, chondrocyte
      hypertrophy and cartilage calcification that are associated with DJD
      pathogenesis.

PMID- 22453524
TI  - Increased prevalence of simple renal cysts in patients with gout.
AB  - The aim of this study was to determine the prevalence of simple renal cysts in
      gout patients and evaluate associated risk factors for its development. Hundred
      and forty-six patients followed at our outpatient Gout Unit and 47 sex- and age
      matched healthy kidney donors who had undergone routine renal ultrasonography,
      using a static gray scale and real-time B-mode units with a 3.5- or 5.0-MHz
      transducer, were evaluated for the presence of renal cysts. Demographic and
      clinical characteristics of gout patients were evaluated considering possible
      risk factors for the occurrence of simple renal cysts such as age, male gender,
      hypertension, and renal impairment. The prevalence of simple renal cyst was 26.0
      % in gout patients and 10.6 % in control group (P = 0.045). Gout patients with
      simple renal cysts presented less renal lithiasis than those without this
      complication (5.2 vs 25.9 %; P = 0.003) in spite of an overall higher frequency
      of renal stones in gout patients compared to control group (20.5 vs. 6.3 %, P =
      0.025). The presence of simple renal cyst in gout was not associated with
      previously reported factors such as age (P = 0.296), male predominance (P =
      0.688), hypertension (P = 0.314), and renal impairment (P = 254). Moreover, no
      association with disease duration (P = 0.843) or tophi (P = 0.616) was observed.
      In conclusion, gout patients have an increased prevalence of simple renal cysts
      associated with a lower occurrence of nephrolithiasis. Whether renal cysts have
      any protective effect in the development of nephrolithiasis in gout remains to be
      determined.

PMID- 22453525
TI  - Lack of association of single nucleotide polymorphisms in toll-like receptors 2
      and 4 with enthesitis-related arthritis category of juvenile idiopathic arthritis
      in Indian population.
AB  - Toll-like receptors 2 and 4 are over expressed in patients with enthesitis
      related arthritis and cause increased production of pro-inflammatory cytokines.
      This aberrant functioning could be due to polymorphisms in TLR2 and TLR4. Hence,
      we genotyped ERA patients for Arg753Gln and Arg677Trp polymorphism in TLR2 gene
      and Asp299Gly and Thr399Ile polymorphism in TLR4 gene. DNA was extracted from
      blood from ERA patients and healthy controls. All four polymorphisms were studied
      by PCR-RFLP method. 200 healthy controls and 97 ERA patients were enrolled. All
      healthy controls and patients had wild-type allele for Arg753Gln and Arg677Trp
      TLR2 polymorphism. Regarding TLR4, Asp299Gly polymorphism A allele frequency was
      90 % in controls and 96 % in patients (OR 2.7, 95 % CI 0.81-8.8). GG homozygous
      genotype was detected in one healthy control and was absent from patients. The
      TLR4 Thr399Ileu variant was not detected in patients. Out of 200 healthy
      controls, 10 were heterozygous (5 %) and only one was homozygous for rare variant
      (0.5 %). Polymorphisms in TLR2 and TLR4 are not associated with ERA.

PMID- 22453526
TI  - Effects of calcitonin on knee osteoarthritis and quality of life.
AB  - There has been a recent interest in calcitonin as a potential treatment for
      osteoarthritis, based on its metabolic activities in both bone turnover and
      cartilage. The aim of this study was to evaluate the effects of nasal form
      calcitonin on knee osteoarthritis and quality of life in women who receive
      calcitonin treatment for postmenopausal osteoporosis. Two hundred and twenty
      postmenopausal women, aged between 55 and 65 years with knee pain and knee
      osteoarthritis, graded II-III by using Kellgren-Lawrence radiographic scoring
      system, were included. Western Ontario and McMaster Universities (WOMAC)
      osteoarthritis index, the quality of life questionnaire of the European
      Foundation for Osteoporosis (QALEFFO-41) and visual analog scale were used for
      the algofunctional assessments. Need of rescue analgesic was recorded. Pain (P <
      0.001), stiffness (P < 0.05), functional capability (P < 0.05) and total score of
      WOMAC (P < 0.05) revealed statistically significant improvements after 3 months
      of the treatment and remained consistent throughout 1 year of the treatment
      period. Participants experienced significant reductions in WOMAC perceptions of
      pain (-53 %), joint stiffness (-44 %) and limitations in physical function (-49
      %) at the end of 1 year of calcitonin treatment. Need of rescue analgesic intake
      was reported to have decreased approximately by 60 % at the end of the 1-year
      treatment period. QUALEFFO_41 scores improved: 37.6 (baseline), 30.9 (3 months),
      28.0 (6 months) and 24.4 (1 year). In conclusion, nasal calcitonin treatment
      provided dual action on osteoporosis and osteoarthritis with significant
      improvements in quality of life and algofunctional results in knee
      osteoarthritis.

PMID- 22453527
TI  - Giving rheumatology patients online home access to their electronic medical
      record (EMR): advantages, drawbacks and preconditions according to care
      providers.
AB  - Technology enables patients home access to their electronic medical record (EMR),
      via a patient portal. This study aims to analyse (dis)advantages, preconditions
      and suitable content for this service, according to rheumatology health
      professionals. A two-phase policy Delphi study was conducted. First, interviews
      were performed with nurses/nurse practitioners (n = 9) and rheumatologists (n =
      13). Subsequently, collected responses were quantified, using a questionnaire
      among the interviewees. The following advantages of patient home access to the
      EMR were reported: (1) enhancement of patient participation in treatment, (2)
      increased knowledge and self-management, (3) improved patient-provider
      interaction, (4) increased patient safety, and (5) better communication with
      others. Foreseen disadvantages of the service included: (1) problems with
      interpretation of data, (2) extra workload, (3) a change in consultation content,
      and (4) disturbing the patient-provider interaction. Also, the following
      preconditions emerged from the data: (1) optimal security, (2) no extra record,
      but a patient-accessible section, (3) no access to clinical notes, and (4) a lag
      time on the release of lab data. Most respondents reported that data on
      diagnosis, medication, treatment plan and consultations could be released to
      patients. On releasing more complex data, such as bodily examinations, lab
      results and radiological images the opinions differed considerably. Providing
      patients home access to their medical record might be a valuable next step into
      patient empowerment and in service towards the patient, provided that security is
      optimal and content and presentation of data are carefully considered.

PMID- 22453528
TI  - Camptocormia as a clinical manifestation of polymyositis/systemic sclerosis
      overlap myositis associated with anti-Ku.
AB  - Camptocormia, an abnormal truncal flexion posture that occurs while walking or
      standing, is usually caused by various hypokinetic movement disorders, mainly
      Parkinson disease. We describe the case of a man with subacute onset of
      camptocormia. Quadriceps muscle biopsy showed significant rhabdomyolysis, few
      isolated inflammatory cells and mild expression of type I MHC in few fibers, a
      pattern usually found in immune-mediated necrotizing myopathies. Myositis was
      associated with Raynaud's phenomenon, mild sclerodactyly, and anti-Ku antibodies
      leading to the diagnosis of polymyositis/systemic sclerosis overlap myositis. The
      posture showed modest improvement in response to treatment. 

PMID- 22453529
TI  - Preliminary report on a study of health-related quality of life in patients with
      rheumatoid arthritis.
AB  - There are studies about health-related quality of life (HRQoL) in patients with
      rheumatoid arthritis (RA), but few studies prospectively assessed HRQoL. The main
      purpose of this study was to analyze HRQoL in patients hospitalized due to RA
      exacerbation and observed over a planned 2-year follow-up in an outpatient
      setting. The study involved 42 women and 9 men, at mean age of 62.5 years (SD +/-
      12.6). The mean duration of the study was 22-23 months. The HRQoL analysis was
      performed using the SF-36 survey. At the beginning of the study, basic data on
      age, sex, selected biochemical (ESR, CRP, GFR, hemoglobin, plasma albumin, plasma
      protein), and clinical parameters (the duration of RA, VAS, DAS28, BMI, the
      presence of cardiovascular disease, diabetes, osteoporosis, osteoporotic
      fractures, osteoarthritis, neoplasm) were collected. Questionnaires were
      completed at the beginning and end of the study. Statistically significant
      reductions in HRQoL scores were observed in social functioning (SF; 0.42 vs 0.32,
      P < 0.05), whereas role-emotional health (RE; 0.48 vs 0.59, P < 0.05) and mental
      health (MH; 0.47 vs 0.54, P < 0.05) scores were increased. A decrease in the SF
      was positively correlated with the lack of osteoporosis at baseline (r = 0.35, P
      > 0.02). An increase in the MH was inversely correlated with BMI (r = -0.31, P <
      0.05), and the level of hemoglobin (r = -0.32, P < 0.028) and positively
      correlated with the presence of osteoarthritis at baseline (r = 0.29, P < 0.05).
      In RA patients, dimensions of HRQoL as SF, RE, and MH could change within 2 years
      and these changes could be related to comorbidities. Although preliminary
      findings are promising, further studies are needed.

PMID- 22453530
TI  - A confusing case: pulmonary lesions including cavities, isolated left heart
      endocarditis and inferior vena cava thrombosis in a patient with perforated
      diverticulitis.
AB  - There are numerous causes of pulmonary cavitary lesions as infection (bacterial,
      parasitic and invasive fungal), Wegener granulomatosis (WG) and other vasculitis,
      sarcoidosis, malignancy, septic thromboembolism, airways disease (cystic
      bronchiectasis and bullae), pneumatoceles and traumatic parenchymal laceration.
      Herein, we present a case with perforated diverticulitis causing pulmonary
      cavitary lesions and a septic thrombus in the neighboring inferior vena cava. 

PMID- 22453531
TI  - Fever of unknown origin: large vessel vasculitis diagnosed by PET/CT.
AB  - PET/CT is starting to play an important role in evaluating fever of unknown
      origin (FUO), due to its ability to localize and delineate areas of high
      metabolic activity, such as neoplastic proliferation and inflammation, including
      vasculitis. We present a case of giant cell arteritis (GCA) in a 72-year-old
      female patient admitted to our department with a 4-month history of FUO, weight
      loss and fatigue, without specific symptoms or signs. Laboratory investigations
      suggested acute phase response, with a pronounced erythrocyte sedimentation rate,
      high CRP level and microcytic anemia. A thorough diagnostic evaluation was
      performed to exclude an unknown primary tumor, which was initially suspected due
      to a positive family history of cancer. Surprisingly, PET/CT revealed large
      vessel vasculitis affecting the ascending, descending and abdominal aorta, as
      well as subclavian, proximal brachial and carotid arteries bilaterally. Biopsy of
      the superficial temporal artery confirmed the diagnosis of GCA. Treatment with
      methylprednisolone and azathioprine led to resolution of clinical symptoms and
      normalization of laboratory parameters. In addition to the use of PET/CT in the
      evaluation of FUO, its value as a method complementary to temporal artery biopsy
      is also discussed. 

PMID- 22453532
TI  - A new method for analyzing diagnostic delay in gynecological cancer.
AB  - OBJECTIVE: The aim of this article is to present a new methodology to illustrate,
      understand, and measure delay in health care. The method is inspired by process
      mapping tools as analytical framework and demonstrates its usefulness for
      studying diagnostic delay in gynecological cancer. MATERIALS AND METHODS: Six
      women with a diagnostic delay of 6 weeks or more before treatment of
      gynecological cancer at a specialized regional department (the Department of
      Gynecology and Obstetrics, Odense University Hospital, Denmark) were included in
      the study. Maps of existing processes were performed for each patient reflecting
      the patients' pathway through the course of the disease. We combined 2 process
      mapping tools, namely, value stream mapping and business process modeling
      notation. The first method identifies the flow in a process as timelines. The
      latter introduces a set of easily recognizable graphical elements. RESULTS:
      Detailed information concerning the cancer patients' pathway was obtained. The
      method visualized the complexities within the diagnostic pathway. The role of
      different participants (patient, general practitioner, and local hospitals)
      became clear by arranging activities according to responsibilities and was shown
      to recurrently influence and contribute to the delay in the diagnostic process.
      Some important contributors to diagnostic delay in gynecological cancer, such as
      lack of cancer suspicion, competing diseases, negative test results, inexpedient
      referral patterns, and referrals without cancer suspicion, were found.
      CONCLUSIONS: Our results point out process mapping tools as a potential
      analytical framework to illustrate, understand, and measure delay in health care.
      Furthermore, the method was able to identify important contributors to the
      diagnostic delay in gynecological cancer patients.

PMID- 22453533
TI  - Video-assisted thoracic surgery for lung cancer.
AB  - Video-assisted thoracic surgery (VATS) lobectomy is currently accepted as an
      appropriate procedure for selected patients with early-stage non-small-cell lung
      cancer (NSCLC). Evidence has demonstrated that VATS lobectomy is not only a safe
      and feasible technique, it provides better functional recovery and oncological
      efficacy similar to that achieved with conventional thoracotomy. However, there
      are still ongoing issues concerning VATS in terms of terminology, oncological
      efficacy, functional recovery, benefit of screening detected lung cancer, and its
      role in limited resection. As the number of VATS procedures are increasing and
      VATS is becoming a dominant procedural choice, it would be wise to collect
      evidence and come to a consensus to justify the expansion of surgical indications
      for VATS.

PMID- 22453534
TI  - Short-term and long-term outcomes of postinfarction ventricular septal
      perforation.
AB  - PURPOSE: Ventricular septal perforation represents a serious complication after
      acute myocardial infarction. This study aimed to evaluate the short-term and
      longterm outcomes of postinfarction ventricular septal perforation (VSP).
      METHODS: We evaluated outcomes for VSP repair for 42 patients over 19 years. A
      retrospective analysis of clinical records, risk factors for hospital death, and
      long-term survival was performed. RESULTS: In-hospital mortality was 33.3%. The
      most common cause of hospital death was left-sided heart failure. A low ejection
      fraction and short time interval from acute myocardial infarction to the onset of
      VSP were significant risk factors. The actuarial survival rates of in-hospital
      survivors at 5 and 10 years were 81.7% and 43.5%, respectively. There were 17
      cardiac events among the survivors during the follow-up period. The most
      influential factor affecting long-term outcomes was the number of diseased
      coronary arteries. CONCLUSION: The long-term survival outcome of VSP patients
      during the postoperative period was comparatively good, but the prognosis of VSP
      patients with multivessel disease was not satisfactory because of congestive
      heart failure or ventricular arrhythmia. We believe that postoperative medical
      treatment for preventing cardiac remodeling is important for improving long-term
      survival outcomes in such patients.

PMID- 22453535
TI  - Insights of stroke in aortic arch surgery: identification of significant risk
      factors and surgical implication.
AB  - PURPOSE: Although the outcomes of aortic arch surgery have improved, stroke
      remains one of the most devastating complications. Therefore, identification of
      true risk factors and understanding the pathogenesis of intraoperative stroke are
      necessary to decrease its occurrence. METHODS: From January 2002 to December
      2010, a total of 251 consecutive patients underwent aortic arch surgery under
      deep hypothermic circulatory arrest and antegrade selective cerebral perfusion in
      our hospital. Hemiarch replacement cases were excluded. Of the remaining
      patients, 190 elective cases that could be reviewed with full perioperative
      clinical data were analyzed. Strokes were classified into three subtypes
      according to their distribution on imaging studies: multiple-embolism type,
      hypoperfusion type, and solitary-embolism type. RESULTS: Operative death occurred
      in 1.1% of patients (2/190), and aortic arch surgery-related in-hospital death
      occurred in 5.3%. Among the 188 survivors, intraoperative strokes occurred in
      5.9%. Multiple-embolism, hypoperfusion type, and solitary-embolism stroke
      occurred in 2.7%, 2.1%, and 1.6%, respectively. Multivariate analysis revealed
      that the risk factor for multiple-embolism stroke was high-grade atheroma in the
      ascending aorta [P < 0.001, odds ratio (OR) 118.0], and that for hypoperfusion
      type stroke was prolonged brain ischemia time over 120 min (P = 0.004, OR 31.5).
      No significant risk factor was found for solitary-embolism stroke. CONCLUSION:
      Intraoperative strokes during elective aortic arch surgery under deep hypothermic
      circulatory arrest and antegrade selective cerebral perfusion are strongly
      influenced by the presence of a high-grade atheroma in the ascending aorta and
      prolonged brain ischemia time. The results suggest that these are key issues to
      reduce stroke in aortic arch surgery.

PMID- 22453536
TI  - Gastric injury caused by low-dose aspirin therapy in consecutive Japanese
      patients: a prospective study.
AB  - PURPOSE: Low-dose aspirin (<325 mg/day), administered to those with several
      conditions involving ischemic disorders, can cause upper gastrointestinal (GI)
      complications. In this prospective study, we aimed to clarify the incidence of
      aspirin-induced gastric ulcers in consecutive Japanese patients and identify
      suitable preventive measures. METHODS: We recruited 125 consecutive adult
      outpatients who received low-dose aspirin (enteric-coated tablets 100 mg) for >8
      weeks. Endoscopy and blood tests were used to evaluate their gastric injury
      (which was scored using a modified Lanza scale) and anti-Helicobacter pylori
      antibody titer, respectively. RESULTS: We found that 39.8% of patients received
      either no upper GI drug or only mucoprotective drugs, 39.8% received medium-dose
      histamine H2 blockers, and 20.4% received proton-pump inhibitors (PPIs). Anti-H.
      pylori antibody titers were positive in 43.7% of patients. The incidence of
      definitive gastric ulcers in this population was 0.97%. Ordered logistic
      regression analysis revealed that the odds ratio for the increase in the modified
      Lanza score was 0.20 for medium-dose histamine H2 blockers and 0.09 for PPIs.
      CONCLUSION: The incidence of postoperative definitive gastric ulcers in Japanese
      patients receiving <=100 mg enteric-coated aspirin was 0.97%. The use of PPIs and
      histamine H(2) blockers may prevent aspirin-induced gastric injury in such
      patients.

PMID- 22453537
TI  - Not palpable? Role of radio-guided video-assisted thoracic surgery for
      nonpalpable solitary pulmonary nodules.
AB  - PURPOSE: This study aimed to evaluate the effectiveness of radio-guided
      localization for thoracoscopic resection of small nonpalpable lung nodules.
      METHODS: Nineteen patients with a solitary nodule were enrolled. Inclusion
      criteria were maximum nodule diameter <15 mm, distance from nearest pleural
      surface of 20-40 mm, nonsolid or partly solid nodule, and/or posterior location.
      Under computed tomography (CT) guidance, the nodule was identified and a needle
      was inserted to reach lesional or perilesional tissue. A solution of (99m)Tc
      macro-aggregates albumin diluted with iodized contrast medium was injected. After
      injection, CT and gamma scintigraphy were performed to confirm precise staining.
      Localization complications were minimal. RESULTS: At thoracoscopy, the gamma
      detector probe allowed localization of nodules in all patients, with the
      radioactive signal being converted by the system into audio and visual numeric
      signals. Resection was performed, and suture margins were checked with the probe
      to search for residual hyperabsorption. All specimens underwent frozen section.
      Mean time to detect nodules with the gamma probe was 6 min (range 3-9 min).
      Frozen section revealed primary pulmonary tumors in eight cases, secondary
      lesions in four cases, and a benign nodule in the remaining seven cases.
      CONCLUSION: Radio-guided localization is a simple, safe procedure for localizing
      nonpalpable solitary pulmonary nodules.

PMID- 22453538
TI  - Inhalation of corticosteroid and beta-agonist for persistent cough following
      pulmonary resection.
AB  - BACKGROUND: Patients undergoing pulmonary resection often suffer from a dry,
      hacking cough, which is usually refractory to opioid cough suppressors such as
      codeine. The cough is often painful and impairs the quality of life of the
      patients. The efficacy of an inhaled corticosteroid plus beta2-agonist against
      the persistent cough after pulmonary resection was evaluated in this study.
      METHODS: We enrolled 21 patients in this prospective study of the efficacy of an
      inhaled corticosteroid plus beta2-agonist against persistent cough following
      pulmonary resection. After baseline evaluation of the severity of the
      postoperative persistent cough using a visual analog scale (VAS), treatment with
      an inhaled corticosteroid plus beta2-agonist was initiated and continued for 2
      weeks. At the end of the 2 weeks, the cough severity was evaluated again using a
      VAS. RESULTS: The median grade of cough on the VAS before the start of the
      inhaled treatment was 4 (range 3-8). At the end of 2 weeks of treatment with an
      inhaled corticosteroid plus beta2 agonist, the median grade of cough on the VAS
      decreased from 4 to 1 (range 0-4). As an adverse effect of the inhalation,
      hoarseness was observed in one patient, which disappeared promptly after
      discontinuing the inhalations. CONCLUSION: Treatment with an inhaled
      corticosteroid plus beta2 agonist appeared to be highly effective, without severe
      adverse effects, against the persistent cough suffered by patients after
      pulmonary resection.

PMID- 22453540
TI  - Advanced effusive-constrictive pericarditis rescued by the aggressive waffle
      procedure.
AB  - We report the case of a 68-year-old man with progressive heart failure due to
      effusive-constrictive pericarditis. During approximately 1 month,
      echocardiography revealed rapid progression from pericarditis with effusion
      without tamponade to pericardial thickening and diastolic dysfunction. Cardiac
      catheterization revealed that the pressure in the right heart chambers remained
      high after pericardiocentesis. The patient was rescued by aggressive
      pericardiectomy and sharp dissection of the epicardium into small fragments. This
      on-pump beating-heart surgery is known as the waffle procedure.

PMID- 22453539
TI  - Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for
      malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals.
AB  - PURPOSE: The treatment of malignant pleural mesothelioma (MPM) remains
      controversial. We present a prospective study of patients treated at our
      institution with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP), and
      radical radiotherapy. METHODS: Patients with MPM who were eligible for EPP and
      multimodality therapy were included in this study. Staging was through computed
      tomography and positron emission tomography and computed tomography (PET/CT)
      scanning, video-assisted thoracoscopic surgery (VATS), and mediastinoscopy. Our
      protocol involved three cycles of cisplatin-based neoadjuvant chemotherapy
      followed by extrapleural pneumonectomy and adjuvant radiotherapy (54 Gy). All
      patients were followed up every 3-6 months until death. RESULTS: From March 2004
      through October 2008, 25 patients were referred for EPP following neoadjuvant
      chemotherapy. EPP was performed in all but three patients, who were found to have
      T4 disease at surgery. Surgical complications included arrhythmias (28%),
      bronchopleural fistulas (12 %), reoperations for bleeding (8%), acute respiratory
      distress syndrome (4%), pneumonia (4%), septicemia (4%), vocal cord palsy (4%),
      and Horner's syndrome (4%). The 30-day mortality was 4%. Adjuvant radiotherapy
      was administered to 81% of patients after EPP. Radiotherapy toxicities included
      thrombocytopenia, radiation pneumonitis, pulmonary embolus, radiation hepatitis,
      herpes zoster, transverse myelitis, and late constrictive pericarditis. Median
      survival from diagnosis was 12.8 months (95% confidence interval 7.8-17.7
      months). One-year survival was 54.5%; 2-year survival was 18.2%. Disease
      progression occurred in 77.3% of patients. Nodal status (N0 disease versus N1-N2)
      or histology (epithelioid versus biphasic) had no significant impact on survival.
      CONCLUSION: Despite recent advances in chemotherapy, surgery, and radiotherapy,
      survival rates remain low for patients with MPM completing multimodality therapy
      including EPP.

PMID- 22453541
TI  - Complete atrioventricular block subsequent to thrombosed-type acute aortic
      dissection.
AB  - We report a case of complete atrioventricular block subsequent to thrombosed-type
      acute aortic dissection. An 81-year-old woman with thrombosed-type acute aortic
      dissection experienced cardiopulmonary arrest and complete atrioventricular block
      6 days after aortic dissection. After temporary pacing, a permanent pacemaker was
      implanted. Atrioventricular conductivity disorders that result in complete
      atrioventricular block are rare complications developing after aortic dissection,
      especially thrombosed-type aortic dissection. We discuss the cause of
      atrioventricular block subsequent to aortic dissection.

PMID- 22453542
TI  - Pseudoaneurysm following percutaneous balloon angioplasty for aortic arch
      recoarctation after the Norwood procedure.
AB  - We experienced a rare case of 5-month-old male infant presenting with a
      pseudoaneurysm following percutaneous balloon angioplasty for aortic arch
      recoarctation after undergoing the Norwood procedure. The pseudoaneurysm, which
      measured 1 cm in diameter, was located between the left carotid artery and the
      left subclavian artery. Under deep hypothermic circulatory arrest, resection of
      the pseudoaneurysm and reconstruction of the neoaortic arch were performed
      successfully.

PMID- 22453543
TI  - Early aortic endograft failure in the presence of periaortic lymphadenopathy with
      neurofibromatosis (von Recklinghausen's disease).
AB  - A 78-year-old man with a history of neurofibromatosis was transferred to our
      hospital for treatment of an abdominal aortic aneurysm. T The patient was treated
      by stent graft implantation and was discharged from the hospital without
      complications. After discharge, the patient reported repeated episodes of
      abdominal pain. Computed tomography performed 3 months postoperatively showed
      localized lymphadenopathy along the graft with extravasation of contrast,
      suggesting the diagnosis of rupture of the aortic aneurysm. Emergent laparotomy
      was performed, which showed penetration of the graft through the aortic wall due
      to deformation of the aorta caused by lymphadenopathy. The lymphadenopathy
      resolved after removal of the graft. This is the first reported case of stent
      graft failure due to aortic deformation associated with neurofibromatosis.

PMID- 22453544
TI  - Single-lung transplantation in a chronic pulmonary emphysema patient with a
      marginal donor who was ABO blood group nonidentical but compatible.
AB  - Because the number of ideal brain-dead donors is limited, active use of marginal
      donors is currently one of the major issues discussed in regard to lung
      transplantation. We report a case in which the patient underwent single-lung
      transplantation for chronic pulmonary emphysema. The lung came from a marginal,
      ABO blood group nonidentical, compatible donor. Because the donor was marginal
      (pneumonia in the right lung and lobar atelectasis in both lungs), all recipient
      candidates with ABO blood group identical declined. Thus, a nonidentical,
      compatible recipient had a chance to receive a lung transplant. This 49-year-old
      man underwent single-lung transplantation for chronic pulmonary emphysema with
      severe respiratory failure. He had a good postoperative clinical course.

PMID- 22453545
TI  - Acute respiratory distress caused by esophageal duplication canceration in an
      adult.
AB  - Esophageal duplication (ED) in adults is rare, and ED canceration is very rare.
      We report a case of acute respiratory embarrassment caused by ED with squamous
      carcinoma in a 39-year-old man and a review of the literature.

PMID- 22453546
TI  - Effects of acupuncture on stress-induced relapse to cocaine-seeking in rats.
AB  - RATIONALE: Cocaine addiction is associated with high rates of relapse, and stress
      has been identified as a major risk factor. We have previously demonstrated that
      acupuncture reduces drug self-administration and dopamine release in the nucleus
      accumbens (NAc), a brain structure implicated in stress-induced reinstatement of
      drug-seeking behavior. OBJECTIVE: This study was conducted to investigate the
      effects of acupuncture on footshock-induced reinstatement of cocaine-seeking and
      the expression of c-Fos and the transcription factor cAMP response element
      binding protein (CREB) in the NAc, used as markers of neuronal activation in
      conditions of stress-induced reinstatement to cocaine. METHODS: Male Sprague
      Dawley rats were trained to self-administer cocaine (1.0 mg/kg) for 14 days,
      followed by extinction and then footshock stress. Acupuncture was applied at
      bilateral Shenmen (HT7) points for 1 min after footshock stress. RESULTS AND
      CONCLUSIONS: Acute footshock stress reinstated cocaine-seeking behavior and
      enhanced c-Fos expression and phosphorylated CREB (pCREB) activation in the NAc
      shell in cocaine pre-exposed rats. On the other hand, acupuncture at HT7, but not
      at control point (LI5), markedly reduced reinstatement of cocaine-seeking (86.5 %
      inhibition vs. control value), c-Fos expression (81.7% inhibition), and pCREB
      activation (79.3% inhibition) in the NAc shell. These results suggest that
      acupuncture attenuates stress-induced relapse by regulating neuronal activation
      in the NAc shell.

PMID- 22453547
TI  - Inhalation of 7.5% carbon dioxide increases alerting and orienting attention
      network function.
AB  - RATIONALE: The development of experimental models that readily translate between
      animals and humans is required to better integrate and clarify the biological,
      behavioural and cognitive mechanisms that underlie normal fear and pathological
      anxiety. Inhalation of low concentrations of carbon dioxide (CO(2)) increases
      anxiety and autonomic arousal in humans, triggers related behaviours in small
      animals, and increases selective attention to threat in healthy humans. However
      the effects on broader cognitive (non-emotional) processes that characterize
      anxiety are not known. OBJECTIVES: To examine the effect of 7.5 % CO(2)
      inhalation (vs. air) on the efficiency of discrete attention networks implicated
      in anxiety: alerting (maintaining an alert state), orienting (the selection of
      information from sensory input) and executive control (resolving cognitive
      conflict). METHODS: Twenty-three healthy human participants completed a
      computerized Attention Network Test (ANT) during inhalation of 7.5 % CO(2)
      enriched and normal/medical air. Gas was administered blind to participants with
      inhalation order counterbalanced across participants. Measures of heart rate,
      blood pressure and subjective mood/anxiety were obtained at baseline and
      following each inhalation period. RESULTS: CO(2) inhalation increased anxiety,
      autonomic arousal and the efficiency of alerting and orienting attention network
      function. Autonomic response to CO(2) correlated with increased orienting; and
      CO(2)-induced anxiety, autonomic arousal and orienting network function increased
      with chronic (trait) anxiety. CONCLUSIONS: Evidence that CO(2) modulates
      attention mechanisms involved in the temporal detection and spatial location of
      salient stimuli converges with evidence that CO(2) triggers fear behaviour in
      animals via direct innervation of a distributed neural network that facilitates
      environmental hypervigilance.

PMID- 22453549
TI  - Novel human monoclonal antibody against epidermal growth factor receptor as an
      imaging probe for hepatocellular carcinoma.
AB  - OBJECTIVE: The epidermal growth factor receptor (EGFR) is overexpressed in many
      epithelial cancers, including hepatocellular carcinoma (HCC), and is an
      attractive target for cancer imaging and therapy. We attempted a novel
      noninvasive imaging method to evaluate anti-EGFR human monoclonal antibody clones
      for determining the uptake of therapeutic anti-EGFR antibody in HCC. METHODS: In
      vitro cell binding of nine I-labeled antibody clones was compared in the human
      epidermoid cancer cell line A431, in three HCC cell lines Hep-G2, SK-Hep1, and
      HuH-7, and in the EGFR-negative control cell line A4. In-labeled or I-labeled 048
      006 was subjected to cell binding, competitive inhibition, and internalization
      assays using A431, SK-Hep1, and HuH-7. Further, In-labeled 048-006 was evaluated
      in in-vivo biodistribution analysis and single-photon imaging in nude tumor
      bearing mice. RESULTS: The 048-006 clone showed the highest binding to EGFR
      expressing cells among the nine antibodies. In-labeled or I-labeled 048-006
      specifically bound to EGFR-expressing cells with high affinity and was
      internalized after binding to EGFR. A431 and HuH-7 tumors showed high In-labeled
      048-006 uptake, which was visualized by single-photon imaging. CONCLUSION:
      Radiolabeled human anti-EGFR monoclonal antibody 048-006 has the potential to be
      a safer imaging probe for predicting tumor uptake of anti-EGFR antibody
      therapeutic agents in HCC.

PMID- 22453554
TI  - Chairman's Message.

PMID- 22453551
TI  - NC1101, a novel tetrahydropyrimidine-containing bleomycin analog from
      Streptomyces verticillus var. pingyangensis n. var.

PMID- 22453555
TI  - Cell-specific distributions of estrogen receptor alpha (ERalpha) and androgen
      receptor (AR) in anterior pituitary glands from adult cockerels as revealed by
      immunohistochemistry.
AB  - Estrogens and androgens play important roles in regulating the hormone-secreting
      functions of the pituitary gland by binding to their corresponding receptors.
      However, the expression of estrogen receptors (ERs) and the androgen receptor
      (AR) and the cell types containing ERs and AR in the anterior pituitary gland of
      adult chickens have not been well-studied. In this study, the distribution of
      ERalpha, AR and their corresponding cell types in the anterior pituitary gland of
      adult cockerels was detected by immunohistochemistry. The results showed that
      ERalpha was expressed in 68.63 % of luteinizing hormone (LH) producing cells but
      was not found in thyrotropes, lactotropes, somatotropes, corticotropes and
      folliculo-stellate (FS) cells. Pituitary hormone and AR double labeling results
      showed that about 37 % of LH cells and 50 % of thyroid-stimulating hormone (TSH)
      producing cells expressed AR, respectively. In contrast, less than 1 % of the
      somatotropes had an AR positive signal and AR signals were not detected in
      lactotropes, corticotropes or FS cells. In addition, there were only a few AR and
      ERalpha dual-labeled cells observed. These novel results provide evidence for a
      cell-specific distribution of ERalpha and AR in the anterior pituitary from adult
      cockerels by immunohistochemistry. The different distributions of ERalpha and AR
      in the LH cells suggest that the feedback-regulating mechanisms of estrogen and
      androgen on the pituitary hormones secretion are different. The functions and
      related mechanisms still need to be elucidated further.

PMID- 22453556
TI  - The cover. La malinche (young girl of Jalala, Oaxaca).

PMID- 22453557
TI  - Studies examine fetal surgery trade-offs, drug interactions, and uterine rupture.

PMID- 22453558
TI  - Cancer experts recommend introducing palliative care at time of diagnosis.

PMID- 22453559
TI  - Birth cohort screening may help find hepatitis C cases.

PMID- 22453560
TI  - Androgen deprivation therapy for prostate cancer and cardiovascular death.

PMID- 22453561
TI  - Cost of health care and the role of physicians.

PMID- 22453562
TI  - Accelerated aging of US presidents.

PMID- 22453563
TI  - Mortality in adults with sickle cell disease and pulmonary hypertension.

PMID- 22453564
TI  - Are medical conferences useful? And for whom?

PMID- 22453565
TI  - Screening for HCV infection in jails.

PMID- 22453566
TI  - Toward innovative models of health care and financing: matchmaking in Maryland.

PMID- 22453567
TI  - A piece of my mind. Our ubiquitous technology.

PMID- 22453568
TI  - One vs three years of adjuvant imatinib for operable gastrointestinal stromal
      tumor: a randomized trial.
AB  - CONTEXT: Adjuvant imatinib administered for 12 months after surgery has improved
      recurrence-free survival (RFS) of patients with operable gastrointestinal stromal
      tumor (GIST) compared with placebo. OBJECTIVE: To investigate the role of
      imatinib administration duration as adjuvant treatment of patients who have a
      high estimated risk for GIST recurrence after surgery. DESIGN, SETTING, AND
      PATIENTS: Patients with KIT-positive GIST removed at surgery were entered between
      February 2004 and September 2008 to this randomized, open-label phase 3 study
      conducted in 24 hospitals in Finland, Germany, Norway, and Sweden. The risk of
      GIST recurrence was estimated using the modified National Institutes of Health
      Consensus Criteria. INTERVENTION: Imatinib, 400 mg per day, orally for either 12
      months or 36 months, started within 12 weeks of surgery. MAIN OUTCOME MEASURES:
      The primary end point was RFS; the secondary end points included overall survival
      and treatment safety. RESULTS: Two hundred patients were allocated to each group.
      The median follow-up time after randomization was 54 months in December 2010.
      Diagnosis of GIST was confirmed in 382 of 397 patients (96%) in the intention-to
      treat population at a central pathology review. KIT or PDGFRA mutation was
      detected in 333 of 366 tumors (91%) available for testing. Patients assigned for
      36 months of imatinib had longer RFS compared with those assigned for 12 months
      (hazard ratio [HR], 0.46; 95% CI, 0.32-0.65; P < .001; 5-year RFS, 65.6% vs
      47.9%, respectively) and longer overall survival (HR, 0.45; 95% CI, 0.22-0.89; P
      = .02; 5-year survival, 92.0% vs 81.7%). Imatinib was generally well tolerated,
      but 12.6% and 25.8% of patients assigned to the 12- and 36-month groups,
      respectively, discontinued imatinib for a reason other than GIST recurrence.
      CONCLUSION: Compared with 12 months of adjuvant imatinib, 36 months of imatinib
      improved RFS and overall survival of GIST patients with a high risk of GIST
      recurrence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00116935.

PMID- 22453569
TI  - Out-of-pocket medication costs and use of medications and health care services
      among children with asthma.
AB  - CONTEXT: Health plans have implemented policies to restrain prescription
      medication spending by shifting costs toward patients. It is unknown how these
      policies have affected children with chronic illness. OBJECTIVE: To analyze the
      association of medication cost sharing with medication and hospital services
      utilization among children with asthma, the most prevalent chronic disease of
      childhood. DESIGN, SETTING, AND PATIENTS: Retrospective study of insurance claims
      for 8834 US children with asthma who initiated asthma control therapy between
      1997 and 2007. Using variation in out-of-pocket costs for a fixed "basket" of
      asthma medications across 37 employers, we estimated multivariate models of
      asthma medication use, asthma-related hospitalization, and emergency department
      (ED) visits with respect to out-of-pocket costs and child and family
      characteristics. MAIN OUTCOME MEASURES: Asthma medication use, asthma-related
      hospitalizations, and ED visits during 1-year follow-up. RESULTS: The mean annual
      out-of-pocket asthma medication cost was $154 (95% CI, $152-$156) among children
      aged 5 to 18 years and $151 (95% CI, $148-$153) among those younger than 5 years.
      Among 5913 children aged 5 to 18 years, filled asthma prescriptions covered a
      mean of 40.9% of days (95% CI, 40.2%-41.5%). During 1-year follow-up, 121
      children (2.1%) had an asthma-related hospitalization and 220 (3.7%) had an ED
      visit. Among 2921 children younger than 5 years, mean medication use was 46.2% of
      days (95% CI, 45.2%-47.1%); 136 children (4.7%) had an asthma-related
      hospitalization and 231 (7.9%) had an ED visit. An increase in out-of-pocket
      medication costs from the 25th to the 75th percentile was associated with a
      reduction in adjusted medication use among children aged 5 to 18 years (41.7%
      [95% CI, 40.7%-42.7%] vs 40.3% [95% CI, 39.4%-41.3%] of days; P = .02) but no
      change among younger children. Adjusted rates of asthma-related hospitalization
      were higher for children aged 5 to 18 years in the top quartile of out-of-pocket
      costs (2.4 [95% CI, 1.9-2.8] hospitalizations per 100 children vs 1.7 [95% CI,
      1.3-2.1] per 100 in bottom quartile; P = .004) but not for younger children.
      Annual adjusted rates of ED use did not vary across out-of-pocket quartiles for
      either age group. CONCLUSION: Greater cost sharing for asthma medications was
      associated with a slight reduction in medication use and higher rates of asthma
      hospitalization among children aged 5 years or older.

PMID- 22453570
TI  - Electrophysiological study with prophylactic pacing and survival in adults with
      myotonic dystrophy and conduction system disease.
AB  - CONTEXT: Up to one-third of patients with myotonic dystrophy type 1 die suddenly.
      Thus far, no intervention has effectively prevented sudden death. OBJECTIVE: To
      determine whether an invasive strategy based on systematic electrophysiological
      studies and prophylactic permanent pacing is associated with longer survival in
      patients presenting with myotonic dystrophy type 1 and major infranodal
      conduction delays than a noninvasive strategy. DESIGN, SETTING, AND PATIENTS: A
      retrospective study, the DM1 Heart Registry included 914 consecutive patients
      older than 18 years with genetically confirmed myotonic dystrophy type 1 who were
      admitted to the Neurological Unit of the Myology Institute of Pitie-Salpetriere
      Hospital, a teaching medical center in Paris, France, between January 2000 and
      December 2009. INTERVENTIONS: Among 486 patients whose electrocardiogram showed a
      PR interval greater than 200 milliseconds, a QRS duration greater than 100
      milliseconds, or both, the outcome of 341 (70.2%) who underwent an invasive
      strategy was compared with 145 (29.8%) who underwent a noninvasive strategy. A
      propensity score risk adjustment and propensity-based matching analysis was used
      to account for selection biases. MAIN OUTCOME MEASURES: Rates of overall survival
      (main outcome measure) and sudden death, respiratory death, and other deaths
      (secondary outcome measures). RESULTS: Over a median follow-up of 7.4 years
      (range, 0-9.9 years), 50 patients died in the invasive strategy group and 30 died
      in the noninvasive strategy group (hazard ratio [HR], 0.74 [95 CI, 0.47-1.16]; P
      = .19), corresponding to an overall 9-year survival of 74.4% (95% CI, 69.2%
      79.9%). Regardless of the technique used to adjust for between-group differences
      in baseline characteristics, the invasive strategy was associated with a longer
      survival, with adjusted HRs ranging from 0.47 (95% CI, 0.26-0.84; P = .01) for a
      covariate-adjusted analysis of propensity-matched data to 0.61 (95% CI, 0.38
      0.99; P = .047) for an analysis adjusted for propensity score quintiles. The
      survival difference was largely attributable to a lower incidence of sudden
      death, which occurred in 10 patients in the invasive strategy group and in 16
      patients in the noninvasive strategy group, with HRs ranging from 0.24 (95% CI,
      0.10-0.56; P = .001) for an analysis adjusted for propensity score quintiles and
      covariates to 0.28 (95% CI, 0.13-0.61; P = .001) for an unadjusted analysis of
      propensity-matched data. CONCLUSION: Among patients with myotonic dystrophy type
      1, an invasive strategy was associated with a higher rate of 9-year survival than
      a noninvasive strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01136330.

PMID- 22453571
TI  - Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels
      with risk of cardiovascular events among patients treated with statins: a meta
      analysis.
AB  - CONTEXT: The associations of low-density lipoprotein cholesterol (LDL-C), non
      high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB)
      levels with the risk of cardiovascular events among patients treated with statin
      therapy have not been reliably documented. OBJECTIVE: To evaluate the relative
      strength of the associations of LDL-C, non-HDL-C, and apoB with cardiovascular
      risk among patients treated with statin therapy. DESIGN: Meta-analysis of
      individual patient data from randomized controlled statin trials in which
      conventional lipids and apolipoproteins were determined in all study participants
      at baseline and at 1-year follow-up. DATA SOURCES: Relevant trials were
      identified by a literature search updated through December 31, 2011.
      Investigators were contacted and individual patient data were requested and
      obtained for 62,154 patients enrolled in 8 trials published between 1994 and
      2008. DATA EXTRACTION: Hazard ratios (HRs) and corresponding 95% CIs for risk of
      major cardiovascular events adjusted for established risk factors by 1-SD
      increase in LDL-C, non-HDL-C, and apoB. RESULTS: Among 38,153 patients allocated
      to statin therapy, 158 fatal myocardial infarctions, 1678 nonfatal myocardial
      infarctions, 615 fatal events from other coronary artery disease, 2806
      hospitalizations for unstable angina, and 1029 fatal or nonfatal strokes occurred
      during follow-up. The adjusted HRs for major cardiovascular events per 1-SD
      increase were 1.13 (95% CI, 1.10-1.17) for LDL-C, 1.16 (95% CI, 1.12-1.19) for
      non-HDL-C, and 1.14 (95% CI, 1.11-1.18) for apoB. These HRs were significantly
      higher for non-HDL-C than LDL-C (P = .002) and apoB (P = .02). There was no
      significant difference between apoB and LDL-C (P = .21). CONCLUSION: Among statin
      treated patients, on-treatment levels of LDL-C, non-HDL-C, and apoB were each
      associated with risk of future major cardiovascular events, but the strength of
      this association was greater for non-HDL-C than for LDL-C and apoB.

PMID- 22453572
TI  - Blue sclerae.

PMID- 22453573
TI  - Optimal duration of adjuvant therapy for patients with resected gastrointestinal
      stromal tumors.

PMID- 22453574
TI  - Medication cost sharing and health outcomes in children with asthma.

PMID- 22453575
TI  - JAMA patient page. Peptic ulcer disease.

PMID- 22453578
TI  - JDD: celebrating 10 years of publishing excellence.

PMID- 22453577
TI  - Creating transient cell membrane pores using a standard inkjet printer.
AB  - Bioprinting has a wide range of applications and significance, including tissue
      engineering, direct cell application therapies, and biosensor microfabrication.
      Recently, thermal inkjet printing has also been used for gene transfection. The
      thermal inkjet printing process was shown to temporarily disrupt the cell
      membranes without affecting cell viability. The transient pores in the membrane
      can be used to introduce molecules, which would otherwise be too large to pass
      through the membrane, into the cell cytoplasm. The application being demonstrated
      here is the use of thermal inkjet printing for the incorporation of fluorescently
      labeled g-actin monomers into cells. The advantage of using thermal ink-jet
      printing to inject molecules into cells is that the technique is relatively
      benign to cells. Cell viability after printing has been shown to be similar to
      standard cell plating methods. In addition, inkjet printing can process thousands
      of cells in minutes, which is much faster than manual microinjection. The pores
      created by printing have been shown to close within about two hours. However,
      there is a limit to the size of the pore created (~10 nm) with this printing
      technique, which limits the technique to injecting cells with small proteins
      and/or particles. A standard HP DeskJet 500 printer was modified to allow for
      cell printing. The cover of the printer was removed and the paper feed mechanism
      was bypassed using a mechanical lever. A stage was created to allow for placement
      of microscope slides and coverslips directly under the print head. Ink cartridges
      were opened, the ink was removed and they were cleaned prior to use with cells.
      The printing pattern was created using standard drawing software, which then
      controlled the printer through a simple print command. 3T3 fibroblasts were grown
      to confluence, trypsinized, and then resuspended into phosphate buffered saline
      with soluble fluorescently labeled g-actin monomers. The cell suspension was
      pipetted into the ink cartridge and lines of cells were printed onto glass
      microscope cover slips. The live cells were imaged using fluorescence microscopy
      and actin was found throughout the cytoplasm. Incorporation of fluorescent actin
      into the cell allows for imaging of short-time cytoskeletal dynamics and is
      useful for a wide range of applications.

PMID- 22453579
TI  - The study of skin of color in dermatology.

PMID- 22453581
TI  - Treatment of moderate to severe acne vulgaris in a Hispanic population: a post
      hoc analysis of efficacy and tolerability of clindamycin phosphate 1.2%/benzoyl
      peroxide 2.5% gel.
AB  - BACKGROUND: Acne in Hispanics is an increasing problem, presenting unique
      challenges. Although combination therapy is now a standard of care in acne,
      concerns exist with the increased potential irritation and dryness in this
      population and the potential for hyperpigmentation. There is a paucity of
      clinical studies that evaluate the efficacy and tolerability of acne medications
      in Hispanics. METHODS: A post-hoc analysis of efficacy and cutaneous tolerability
      in 458 Hispanic subjects receiving clindamycin phosphate 1.2%/BPO 2.5% gel,
      individual active ingredients and vehicle from two 12-week multicenter double
      blind studies that enrolled 2813 subjects with moderate to severe acne. RESULTS:
      Median reductions in inflammatory lesions, noninflammatory, and total lesions
      (71.6%, 50.9% and 55.1%, respectively) were significantly greater with
      clindamycin phosphate 1.2%/BPO 2.5% gel versus the individual active ingredients
      and vehicle. Treatment success (35.6% "clear/almost clear") and patient
      satisfaction (83.2%) were also significantly greater than vehicle at week 12.
      Cutaneous tolerability was excellent with all mean scores less than or equal to
      0.2 at week 12 (where 1=mild). CONCLUSIONS: Overall efficacy and tolerability
      with clindamycin phosphate 1.2%/BPO 2.5% gel were better in the Hispanic
      population compared to the total study population. Hispanic acne subjects were
      not found to be more susceptible to cutaneous irritation from treatment with
      clindamycin phosphate 1.2%/BPO 2.5% gel and both efficacy and tolerability was
      excellent.

PMID- 22453582
TI  - Cultural competence and unique concerns in patients with ethnic skin.
AB  - The projections of increases in the number of skin of color patients over the
      next several decades, necessitates expertise in cultural competence for health
      care providers. Acquiring competency begins with practitioners reflecting on
      their self identity and personal beliefs. Additionally, understanding African
      American cultural habits and practices and their impact on disease is critically
      important. We review, in this article, the fundamentals of becoming cultural
      competent. Patients are best served when their physician embraces their culture,
      their view of the health care system as well as habits and practices.

PMID- 22453583
TI  - Top dermatologic conditions in patients of color: an analysis of nationally
      representative data.
AB  - BACKGROUND: Some dermatologic disorders are known to be much more common in
      patients of color, but the leading dermatologic disorders in patients of color
      have not yet been described on the basis of nationally representative data.
      PURPOSE: To determine the leading dermatologic disorders for each major racial
      and ethnic group in the United States. METHODS: We queried the National
      Ambulatory Medical Care Survey (NAMCS) for the leading diagnoses in patient
      visits to U.S. dermatologists from 1993 to 2009. The leading diagnoses were
      tabulated for each racial and ethnic group, and the top conditions were compared
      between groups. In a separate analysis, visits for skin conditions regardless of
      physician specialty were analyzed for leading diagnoses in each racial and ethnic
      group. RESULTS: The top five diagnoses for African-American patients in
      dermatology clinics were acne, unspecified dermatitis or eczema, seborrheic
      dermatitis, atopic dermatitis, and dyschromia. For Asian or Pacific Islander
      patients, the top five were acne, unspecified dermatitis or eczema, benign
      neoplasm of skin, psoriasis, and seborrheic keratosis. By contrast, in Caucasian
      patients, the top five were actinic keratosis, acne, benign neoplasm of skin,
      unspecified dermatitis or eczema, and nonmelanoma skin cancer. In Hispanic
      patients of any race, the leading diagnoses were acne, unspecified dermatitis or
      eczema, psoriasis, benign neoplasm of skin, and viral warts. When the leading
      dermatologic diagnoses across all physician specialties were assessed, the top
      diagnoses for African-Americans were unspecified dermatitis or eczema, acne,
      dermatophytosis of scalp and beard, sebaceous cyst, and cellulitis or abscess;
      for Asians or Pacific Islanders were unspecified dermatitis or eczema, acne,
      atopic dermatitis, urticaria, and psoriasis; and for Caucasians were acne,
      unspecified dermatitis or eczema, actinic keratosis, viral warts, and sebaceous
      cyst. For Hispanics of any race, they were unspecified dermatitis or eczema,
      acne, sebaceous cyst, viral warts, and cellulitis or abscess. For a sole
      diagnosis of a dermatologic condition, only 28.5% of African-Americans' visits
      and 23.9% of Hispanics' visits were to dermatologists, as compared to 36.7% for
      Asians and Pacific Islanders and 43.2% for Caucasians. LIMITATIONS: The data are
      based on numbers of ambulatory care visits rather than numbers of patients. Data
      on race or ethnicity were not collected for some patients. CONCLUSIONS: Several
      dermatologic disorders are much more commonly seen in patients of color. Acne and
      unspecified dermatitis or eczema are in the top five for all major U.S. racial
      and ethnic groups. There may be an opportunity to improve the care of patients of
      color by ensuring they have equal access to dermatologists.

PMID- 22453584
TI  - Electroplaning of non-inflammatory linear verrucous epidermal nevi (LVEN).
AB  - BACKGROUND: The non-inflammatory linear verrucous subtype of epidermal nevi
      (LVEN) although generally benign, can be aesthetically displeasing and
      functionally disfiguring to patients. OBJECTIVE: To provide a permanent
      improvement in the clinical appearance of LVEN with minimal scarring. METHOD:
      Electroplaning with Surgitron(r) FFPF EMC was the chosen method of treatment.
      RESULTS: Electroplaning is a simple, safe, and effective method for improving the
      appearance of non-inflammatory linear epidermal nevi.

PMID- 22453585
TI  - Psoriasis in African-Americans: a caregivers' survey.
AB  - BACKGROUND: Psoriasis is a common skin disease in Caucasians but less common in
      African-Americans. AIMS: Our aim is to evaluate caregiver opinions regarding the
      clinical presentations and treatment of psoriasis in African-Americans compared
      to Caucasians. PATIENTS/METHODS: A survey was sent to 29 dermatologists who are
      opinion leaders in the field of psoriasis. The survey included a number of
      questions regarding the characteristics of the patients seen in their practice.
      RESULTS: A total of 29 surveys were completed and returned. All of the
      dermatologists use the extent of disease as a criterion to determine the severity
      of the disease. Other criteria include scale, thickness, erythema, associated
      general symptoms, and dyspigmentation. About 66% of the respondents reported the
      different manifestations of disease, such as more dyspigmentation, thicker
      plaques, and less erythema in African-Americans. The most common first-line
      treatments for mild to moderate disease were highpotency topical steroids (68%)
      followed by topical vitamin D analogues (41%). For moderate to severe disease,
      the most commonly used first-line treatments were high-potency topical steroids
      (54%) and phototherapy (46%). CONCLUSIONS: The clinical manifestations of
      psoriasis in African-Americans are not exactly the same as in Caucasians.
      Physicians should be aware of the difference in clinical manifestations in
      African-Americans. Further research and large-scale studies are necessary to
      elucidate the differences in the clinical presentation, natural course of the
      disease, and the criteria used for the evaluation of severity among ethnic
      groups.

PMID- 22453586
TI  - Basal cell carcinoma in skin of color.
AB  - Non-melanoma skin cancer most commonly affects Caucasians, and only rarely
      affects darker-skinned individuals. However, skin cancer in these groups is
      associated with greater morbidity and mortality. Ultraviolet radiation is the
      major etiologic factor in basal cell carcinoma (BCC) and likely plays a pivotal
      role in the development of other forms of skin cancer. Yet it is commonly thought
      among patients as well as physicians that darker pigmentation inherently affords
      complete protection from skin cancer development. This low index of suspicion
      results in delayed diagnoses and poorer outcomes. This review follows a detailed
      computer search that cross-matched the diagnosis of BCC with skin color type in a
      large commercial dermatopathology facility. The reported skin types, all
      Fitzpatrick skin types IV, V, and VI, and histories were confirmed. A
      predominance of pigmented BCCs was found in sun-exposed areas of these older
      individuals. Although less common in darker-skinned ethnic groups, BCC does occur
      and can pose significant morbidity. Thus, it is essential that dermatologists are
      familiar with the epidemiology and clinical presentation of all cutaneous
      malignancies in darker skin so that these patients are fully aware of risks as
      well as prevention of the disease.

PMID- 22453587
TI  - Treatment of impetigo: oral antibiotics most commonly prescribed.
AB  - BACKGROUND: Impetigo is a highly contagious, superficial skin disease that is
      frequently seen in children. While data support the use of topical antibiotics
      for treatment, the medications actually prescribed in practice are not well
      documented. OBJECTIVES: To determine the prescribing pattern of dermatologists
      and nondermatologists when treating impetigo and the demographics of the patients
      treated. METHODS: National Ambulatory Medical Care Survey data on office visits
      for impetigo were analyzed from 1997 to 2007. Patient demographics and the
      treatments for impetigo were recorded. RESULTS: During this 10-year period,
      dermatologists managed an estimated 274,815 impetigo visits and nondermatologists
      an estimated 3,722,462 visits. Both dermatologists and nondermatologists most
      frequently prescribed oral antibiotics to treat impetigo. Topical antibiotics
      were second most common, and a variety of combination treatments were used.
      CONCLUSIONS: Oral antibiotics are the most common class of medications used to
      treat impetigo. There is an opportunity for physicians to take advantage of the
      equally efficacious topical antibiotics for treating impetigo. A shift towards
      topical antibiotics would likely decrease morbidity (resulting from adverse
      effects) associated with use of oral agents.

PMID- 22453588
TI  - Treating onychomycoses of the toenail: clinical efficacy of the sub-millisecond
      1,064 nm Nd: YAG laser using a 5 mm spot diameter.
AB  - BACKGROUND: Onychomycosis is a relatively common fungal infection. Current
      treatments have limited applicability and low cure rates. Recently introduced
      laser therapy has shown to be a safe and effective treatment for onychomycosis.
      In this study, we evaluate a submillisecond Nd:YAG 1,064 nm laser for treating
      onychomycoses of the tonail. METHODS: Thirteen subjects (9 female, 4 male) with
      37 affected toenails received 1 to 3 treatments 4 and/or 8 weeks apart with a sub
      millisecond 1,064 nm Nd:YAG laser. Diagnosis of onychomycosis was confirmed with
      microscopy. Average follow-up time was 16 weeks post-final treatment. Photos were
      taken and degree of turbidity was determined using a turbidity scale (ranging
      from "0 = clear nail" to "10 = completely turbid nail") at each visit.
      Improvement in turbidity was determined by comparison of turbidity scores at
      baseline and 16-week follow-up on average. Efficacy was assessed by an overall
      improvement scale (0 to 4), which combined improvement in turbidity scores and
      microscopic examination. Overall improvement was classified as "4 = complete
      clearance" if the turbidity score indicated "0 = clear nail" accompanied by a
      negative microscopic result. No microscopic examination was performed unless the
      turbidity score showed "0 = clear nail." RESULTS: Treatments were well tolerated
      by all subjects and there were no adverse events. Of the 37 toenails treated, 30
      (81%) had "moderate" to "complete" clearance average of 16 weeks post-final
      treatment. Nineteen toenails (51%) were completely clear and all tested negative
      for fungal infection on direct microscopic analysis. Seven (19%) toenails had
      significant clearance and four (11%) had moderate clearance. CONCLUSIONS: The
      preliminary results of this study show this treatment modality is safe and
      effective for the treatment of onychomycosis in the short term. Additional
      studies are needed to more fully assess the clinical and mycological benefits as
      well as optimize the treatment protocol and parameters.

PMID- 22453589
TI  - Effect of dietary zinc and phytase supplementation on botulinum toxin treatments.
AB  - PURPOSE: To determine whether oral zinc supplementation might affect the efficacy
      and duration of botulinum toxin treatments. METHODS: In a double-blind, placebo
      controlled, crossover pilot study, we examined the efficacy of three botulinum
      toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, and
      rimabotulinumtoxinB) following oral supplementation with zinc citrate 50 mg and
      phytase 3,000 PU, zinc gluconate 10 mg, or lactulose placebo in individuals
      treated for cosmetic facial rhytids, benign essential blepharospasm, and
      hemifacial spasm. RESULTS: In seventy-seven patients, 92% of subjects
      supplemented with zinc 50 mg and phytase experienced an average increase in toxin
      effect duration of nearly 30%, and 84% of participants reported a subjective
      increase in toxin effect, whereas no significant increase in duration or effect
      was reported by patients following supplementation with lactulose placebo or 10
      mg of zinc gluconate. The dramatic impact of the zinc/phytase supplementation on
      some patients' lives clinically unmasked the study and prompted an early
      termination. CONCLUSIONS: This study suggests a potentially meaningful role for
      zinc and/or phytase supplementation in increasing the degree and duration of
      botulinum toxin effect in the treatment of cosmetic facial rhytids, benign
      essential blepharospasm, and hemifacial spasm.

PMID- 22453591
TI  - Defying consensus: correct sizing of full-thickness skin grafts.
AB  - BACKGROUND: Full-Thickness skin grafts are routinely used to reconstruct defects
      throughout the body. When planning the size of the graft, the surgeon usually
      copies a template from the defect and measures the graft to fit its full
      dimensions. This may lead to an oversized graft, resulting an unaesthetic
      outcome. OBJECTIVE: To evaluate discrepancy in size between the excised full
      thickness skin and the excision (donor) site. METHODS: Data from 20 cases of full
      thickness excisions was reviewed and analyzed. RESULTS: There was a considerable
      difference in length of both the short and long axes between the excised full
      thickness skin and the excision site. CONCLUSIONS: The initial size of a full
      thickness skin graft should be smaller than the defect it is planned to cover.

PMID- 22453590
TI  - An open-label pilot study of naftifine 1% gel in the treatment of seborrheic
      dermatitis of the scalp.
AB  - Topical antifungal treatment is a mainstay of therapy for Seborrehic Dermatitis
      (SD). Although the amidazole and ciclopyridine antifungals have been extensively
      studied, few clinical efficacy data are available for topical allylamine therapy
      in SD. The objective of this open-label exploratory study was to evaluate the
      efficacy and safety of natifine HCl 1% gel applied twice daily for 4 weeks, as
      topical treatment of moderate SD of the scalp. Nine subjects (5 men, 4 women)
      with a mean age of 56 (33-81) years with SD of the scalp were enrolled and made 4
      visits to the site. At Visit 1 (Week 0), subjects were screened, enrolled,
      baseline efficacy data were obtained, and treatment was initiated. Subjects
      returned at Week 2, Week 4 (end of treatment), and Week 6 for efficacy and safety
      assessments. Efficacy was evaluated by changes from baseline in investigator
      rated scores on 0-5-grade scales: (1) SD Global Evaluation Scale (SDGES), (2)
      Erythema Severity Scale, (3) Scaling Severity Scale, (4) % Scalp Involvement
      Scale, and subject-rated scores on the (4) Itching Severity Scale, and (5) Global
      Improvement Scale, where 0=none and 5=most severe. Mean severity scores for the
      SDGES and % Scalp Involvement scales progressively declined (improved) 66% and
      54% from respective baseline levels at Week 6. Mean erythema rating decreased 38%
      from baseline and scaling decreased 50% from baseline by Weeks 4 and 6. Itching
      improved in 5 of 9 (56%) subjects by the end of treatment. A total of 8 of 9
      (89%) subjects rated their symptoms as improved from baseline at the end of
      treatment and Week 6. There were no treatment-related adverse events during the
      study. These results suggest that naftifine 1% gel applied twice daily for 4
      weeks is effective and safe topical treatment for moderate SD of the scalp.

PMID- 22453593
TI  - Treatment of Schamberg's disease with advanced fluorescence technology.
AB  - Schamberg's disease is a pigmented purpuric dermatosis that is generally
      asymptomatic, however, patients with Schamberg's disease often seek treatment for
      aesthetic improvement. Many topical and systemic therapies have been tried
      without consistent results. This case series describes the treatment of five
      patients with Schamberg's disease of the lower extremities using Advanced
      Fluorescence Technology (AFT) pulsed light with favorable results.

PMID- 22453596
TI  - Treatment of generalized vitiligo with anti-TNF-alpha Agents.
AB  - BACKGROUND: Although the exact pathogenesis of vitiligo is not fully understood,
      it appears to be an autoimmune disease. It is hypothesized that tumor necrosis
      factor alpha (TNF-?) plays an important role in vitiligo. TNF-? can destroy
      melanocytes through the induction of various apoptotic pathways. In addition, TNF
      ? can inhibit melanocyte stem cell differentiation. OBJECTIVE: To evaluate the
      efficacy and safety of treating vitiligo patients with anti-TNF-? agents.
      METHODS: A total of 6 patients were recruited. All patients had widespread non
      segmental vitiligo. Biologics, including infliximab, etanercept, and adalimumab,
      were given according to treatment regimens used for psoriasis. Photographs were
      taken at the initial visit, every two months during the therapy and then six
      months after therapy completion. RESULTS: All patients completed the treatment;
      two patients were treated with infliximab, two with etanercept, and two with
      adalimumab. All of the biologics were well tolerated throughout the treatment
      period, and none of the patients reported any significant adverse events. Digital
      images were compared before, during and after treatment. Repigmentation of the
      vitiliginous areas was not observed in any of the patients. Vitiligo worsened in
      one patient who was treated with infliximab and developed a psoriasiform rash.
      However, the remaining patients did not develop any new depigmented patches
      during treatment or at the six-month follow-up; vitiligo was considered stable in
      these five patients. CONCLUSIONS: Although the anti-TNF-? agents were well
      tolerated in all six vitiligo patients, efficacy was not observed. Further
      evaluation with larger studies may be required.

PMID- 22453597
TI  - Tumor stage acne keloidalis nuchae treated with surgical excision and secondary
      intention healing.

PMID- 22453598
TI  - Psychology and psychiatry in the dermatologist's office: an approach to delusions
      of parasitosis.
AB  - Most dermatologists will treat at least one patient suffering from delusions of
      parasitosis (DP) in their career.1 These patients are memorable not only for the
      peculiarity of their delusions and their repeated visits to the office, but for
      the challenges they present in their treatment. These patients are also
      frustrating. It seems that if they could only stop scratching, picking and
      manipulating their skin their symptoms would improve. However, these cutaneous
      signs only hint at the underlying psychiatric problem that drives these patients
      to manipulate their skin. These patients seek out the assistance of
      dermatologists and eschew the help of psychiatrists or therapists because they
      believe that they have a primary skin disease. Although the treatment of DP is
      conceptually simple, it is not intuitive. Thus as dermatologists, we should have
      at the ready a full set of dermatologic, psychologic, and pharmacologic tools to
      treat these patients.

PMID- 22453599
TI  - Carnosic acid modulates Akt/IKK/NF-kappaB signaling by PP2A and induces intrinsic
      and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells.
AB  - This study investigates the efficacy of carnosic acid (CA), a polyphenolic
      diterpene, isolated from the plant rosemary (Rosemarinus officinalis), on
      androgen-independent human prostate cancer PC-3 cells. CA induced anti
      proliferative effects in PC-3 cells in a concentration- and time-dependent
      manner, which was due to apoptotic induction as evident from flow-cytometry, DNA
      laddering and TUNEL assay. Apoptosis was associated with the activation of
      caspase-8, -9, -3 and -7, increase in Bax:Bcl-2 ratio, release of cytochrome-c
      and decrease in expression of inhibitor of apoptosis (IAP) family of proteins.
      Apoptosis was attenuated upon pretreatment with specific inhibitors of caspase-8
      (Z-IETD-fmk) and caspase-9 (Z-LEHD-fmk) suggesting the involvement of both
      intrinsic and extrinsic apoptotic cascades. Further, apoptosis resulted from the
      inhibition of IKK/NF-kappaB pathway as evident from decreased DNA binding
      activity, nuclear translocation of p50 and p65 and IkappaBalpha phosphorylation.
      The down-regulation of IKK/NF-kappaB was associated with inhibition of Akt
      phosphorylation and its kinase activity with a concomitant increase in the
      serine/threonine protein phosphatase 2A (PP2A) activity. Pharmacologic inhibition
      of PP2A by okadaic acid and calyculin A, significantly reversed CA-mediated
      apoptotic events in PC-3 cells indicating that CA induced apoptosis by activation
      of PP2A through modulation of Akt/IKK/NF-kappaB pathway. In addition, CA induced
      apoptosis in another androgen refractory prostate cancer DU145 cells via
      intrinsic pathway as evidenced from the activation of caspase 3, cleavage of
      PARP, increase in Bax:Bcl-2 ratio and cytochrome-c release. Carnosic acid,
      therefore, may have the potential for use in the prevention and/or treatment of
      prostate cancer.

PMID- 22453600
TI  - Nonstationary harmonic modeling for ECG removal in surface EMG signals.
AB  - We present a compact approach for mitigating the presence of electrocardiograms
      (ECG) in surface electromyographic (EMG) signals by means of time-variant
      harmonic modeling of the cardiac artifact. Heart rate and QRS complex
      variability, which often account for amplitude and frequency time variations of
      the ECG, are simultaneously captured by a set of third-order constant-coefficient
      polynomials modulating a stationary harmonic basis in the analysis window. Such a
      characterization allows us to significantly suppress ECG from the mixture by
      preserving most of the EMG signal content at low frequencies (less than 20 Hz).
      Moreover, the resulting model is linear in parameters and the least-squares
      solution to the corresponding linear system of equations efficiently provides
      model parameter estimates. The comparative results suggest that the proposed
      method outperforms two reference methods in terms of the EMG preservation at low
      frequencies.

PMID- 22453601
TI  - Time-based compression and classification of heartbeats.
AB  - Heart function measured by electrocardiograms (ECG) is crucial for patient care.
      ECG generated waveforms are used to find patterns of irregularities in cardiac
      cycles in patients. In many cases, irregularities evolve over an extended period
      of time that requires continuous monitoring. However, this requires wireless ECG
      recording devices. These devices consist of an enclosed system that includes
      electrodes, processing circuitry, and a wireless communication block imposing
      constraints on area, power, bandwidth, and resolution. In order to provide
      continuous monitoring of cardiac functions for real-time diagnostics, we propose
      a methodology that combines compression and analysis of heartbeats. The signal
      encoding scheme is the time-based integrate and fire sampler. The diagnostics can
      be performed directly on the samples avoiding reconstruction required by the
      competing finite rate of innovation and compressed sensing. As an added benefit,
      our scheme provides an efficient hardware implementation and a compressed
      representation for the ECG recordings, while still preserving discriminative
      features. We demonstrate the performance of our approach through a heartbeat
      classification application consisting of normal and irregular heartbeats known as
      arrhythmia. Our approach that uses simple features extracted from ECG signals is
      comparable to results in the published literature.

PMID- 22453602
TI  - A new approach for investigating intracranial pressure signal: filtering and
      morphological features extraction from continuous recording.
AB  - Nowadays, the Intracranial Pressure (ICP) monitoring has become the most common
      method of investigation for both traumatic and chronic neural pathologies. ICP
      signals are typically triphasic, that is, in a single waveform, three subpeaks
      can be identified. This work outlines a new algorithm to identify subpeaks from
      the ICP recordings and to extract a number of 20 meaningful parameter trends. The
      validity of the implemented method has been proved through a comparison between
      the automatic subpeaks identification by the algorithm and the manually marked
      subpeaks by a neurosurgeon. The automatic marking system has identified subpeaks
      for the 63.74% (mean value) of pulse waves, providing the position and amplitude
      of each identified subpeak within a tolerance of +/-7 samples. This automatic
      system provides a feature set to be used by classification software to obtain
      more precise and easier diagnosis in all those cases that involve brain damages
      or diseases.

PMID- 22453603
TI  - High-density myoelectric pattern recognition toward improved stroke
      rehabilitation.
AB  - Myoelectric pattern-recognition techniques have been developed to infer user's
      intention of performing different functional movements. Thus electromyogram (EMG)
      can be used as control signals of assisted devices for people with disabilities.
      Pattern-recognition-based myoelectric control systems have rarely been designed
      for stroke survivors. Aiming at developing such a system for improved stroke
      rehabilitation, this study assessed detection of the affected limb's movement
      intention using high-density surface EMG recording and pattern-recognition
      techniques. Surface EMG signals comprised of 89 channels were recorded from 12
      hemiparetic stroke subjects while they tried to perform 20 different arm, hand,
      and finger/thumb movements involving the affected limb. A series of pattern
      recognition algorithms were implemented to identify the intended tasks of each
      stroke subject. High classification accuracies (96.1% +/- 4.3%) were achieved,
      indicating that substantial motor control information can be extracted from
      paretic muscles of stroke survivors. Such information may potentially facilitate
      improved stroke rehabilitation.

PMID- 22453604
TI  - Solid-phase microextraction of 2,4,6-trinitrotoluene using a molecularly
      imprinted-based fiber.
AB  - A molecularly imprinted polymer with trinitrotoluene as the template molecule was
      synthesized and used as the novel coating for solid-phase microextraction of the
      nitroaromatic explosive 2,4,6-trinitrotoluene for its selective determination.
      The fiber was characterized in terms of coating thickness, morphology, intra- and
      inter-batch repeatability and extraction efficiency. An average thickness of 50
      +/- 4 MUm with a uniform distribution of the coating was obtained. Good
      performances of the developed procedure in term of both intra-batch and inter
      batch repeatability with relative standard deviations <8% were obtained. Finally,
      detection and quantitation limits in the low nanogram per kilogram levels were
      achieved proving the superior extraction capability of the developed coating,
      obtaining gas chromatography-mass spectrometry responses about two times higher
      than those achieved using commercial devices.

PMID- 22453605
TI  - Chemiluminescence detection flow cells for flow injection analysis and high
      performance liquid chromatography.
AB  - We have examined a range of new and previously described flow cells for
      chemiluminescence detection. The reactions of acidic potassium permanganate with
      morphine and amoxicillin were used as model systems representing the many fast
      chemiluminescence reactions between oxidising agents and organic analytes, and
      the preliminary partial reduction of the reagent was exploited to further
      increase the rates of reaction. The comparison was then extended to high
      performance liquid chromatography separations of alpha- and beta-adrenergic
      agonists, with permanganate chemiluminescence detection. Flow cells constructed
      by machining novel channel designs into white polymer materials (sealed with
      transparent films or plates) have enabled improvements in mixing efficiency and
      overall transmission of light to the photodetector.

PMID- 22453606
TI  - Industrial research and development for instrumental analytics: requirements,
      skills, strategic objectives.

PMID- 22453607
TI  - A multiplexed screening method for agonists and antagonists of the estrogen
      receptor protein.
AB  - The estrogen receptor (ER) is regarded as a significant drug target because of
      its important physical and pathological function. In this article, we describe a
      novel screening method to obtain agonists and antagonists of ER. ER was
      immobilized onto an aldehyde-modified glass slide. The affinity of Cy3-labeled
      estradiol for ER protein microarrays was then determined. Two libraries, one
      containing 29 synthetic compounds and the other with 384 natural products that
      served as a model, were screened to find new ligands for ER. The IC(50) values
      obtained for tamoxifen and raloxifene were consistent with those found in the
      literature (4.85 * 10(-7) M versus 1.74~4.23 * 10(-7) M and 7.58 * 10(-8) M
      versus 0.89~5.84 * 10(-8) M, respectively). Finally, 65 active ligands (5
      synthetic compounds and 60 natural products) of ER were identified. This novel
      method gave identical results to a conventional fluorescence polarization assay,
      thus verifying the accuracy of this simultaneous multireceptor screening method
      based on protein microarrays. The presented method is sensitive, accurate, and
      reliable, and shows great potential for use in high-throughput drug-screening
      research.

PMID- 22453608
TI  - Physicochemical properties of pH-controlled polyion complex (PIC) micelles of
      poly(acrylic acid)-based double hydrophilic block copolymers and various
      polyamines.
AB  - The physicochemical properties of polyion complex (PIC) micelles were
      investigated in order to characterize the cores constituted of electrostatic
      complexes of two oppositely charged polyelectrolytes. The pH-sensitive micelles
      were obtained with double hydrophilic block copolymers containing a poly(acrylic
      acid) block linked to a modified poly(ethylene oxide) block and various
      polyamines (polylysine, linear and branched polyethyleneimine, polyvinylpyridine,
      and polyallylamine). The pH range of micellization in which both components are
      ionized was determined for each polyamine. The resulting PIC micelles were
      characterized using dynamic light scattering and small-angle X-ray scattering
      experiments (SAXS). The PIC micelles presented a core-corona nanostructure with
      variable polymer density contrasts between the core and the corona, as revealed
      by the analysis of the SAXS curves. It was shown that PIC micelle cores
      constituted by polyacrylate chains and polyamines were more or less dense
      depending on the nature of the polyamine. It was also determined that the density
      of the cores of the PIC micelles depended strongly on the nature of the
      polyamine. These homogeneous cores were surrounded by a large hairy corona of
      hydrated polyethylene oxide block chains. Auramine O (AO) was successfully
      entrapped in the PIC micelles, and its fluorescence properties were used to get
      more insight on the core properties. Fluorescence data confirmed that the cores
      of such micelles are quite compact and that their microviscosity depended on the
      nature of the polyamine. The results obtained on these core-shell micelles allow
      contemplating a wide range of applications in which the AO probe would be
      replaced by various cationic drugs or other similarly charged species to form
      drug nanocarriers or new functional nanodevices.

PMID- 22453611
TI  - A box spline calculus for the discretization of computed tomography
      reconstruction problems.
AB  - B-splines are attractive basis functions for the continuous-domain representation
      of biomedical images and volumes. In this paper, we prove that the extended
      family of box splines are closed under the Radon transform and derive explicit
      formulae for their transforms. Our results are general; they cover all known
      brands of compactly-supported box splines (tensor-product B-splines, separable or
      not) in any number of dimensions. The proposed box spline approach extends to non
      Cartesian lattices used for discretizing the image space. In particular, we prove
      that the 2-D Radon transform of an N-direction box spline is generally a
      (nonuniform) polynomial spline of degree N-1. The proposed framework allows for a
      proper discretization of a variety of tomographic reconstruction problems in a
      box spline basis. It is of relevance for imaging modalities such as X-ray
      computed tomography and cryo-electron microscopy. We provide experimental results
      that demonstrate the practical advantages of the box spline formulation for
      improving the quality and efficiency of tomographic reconstruction algorithms.

PMID- 22453610
TI  - Three-dimensional segmentation of fluid-associated abnormalities in retinal OCT:
      probability constrained graph-search-graph-cut.
AB  - An automated method is reported for segmenting 3-D fluid-associated abnormalities
      in the retina, so-called symptomatic exudate-associated derangements (SEAD), from
      3-D OCT retinal images of subjects suffering from exudative age-related macular
      degeneration. In the first stage of a two-stage approach, retinal layers are
      segmented, candidate SEAD regions identified, and the retinal OCT image is
      flattened using a candidate-SEAD aware approach. In the second stage, a
      probability constrained combined graph search-graph cut method refines the
      candidate SEADs by integrating the candidate volumes into the graph cut cost
      function as probability constraints. The proposed method was evaluated on 15
      spectral domain OCT images from 15 subjects undergoing intravitreal anti-VEGF
      injection treatment. Leave-one-out evaluation resulted in a true positive volume
      fraction (TPVF), false positive volume fraction (FPVF) and relative volume
      difference ratio (RVDR) of 86.5%, 1.7%, and 12.8%, respectively. The new graph
      cut-graph search method significantly outperformed both the traditional graph cut
      and traditional graph search approaches (p < 0.01, p < 0.04) and has the
      potential to improve clinical management of patients with choroidal
      neovascularization due to exudative age-related macular degeneration.

PMID- 22453612
TI  - Overactive bladder syndrome.

PMID- 22453613
TI  - Sensory urgency.
AB  - Overactive bladder is highly prevalent among the general population. This
      article describes the definition, theories of causation, diagnostic tools and
      various treatment options for overactive bladder.

PMID- 22453614
TI  - Efficacy of Solifenacin on Symptom Bother and Health-Related Quality of Life in
      Patients With Acute, Early Chronic, and Late Chronic Overactive Bladder:
      Secondary Analysis of Data From the VOLT Study.
AB  - OBJECTIVES: : In many clinical trials of pharmacotherapy for overactive bladder
      (OAB), the duration of symptoms is reported as a baseline characteristic; none
      has investigated this as a prognostic variable. We evaluated the efficacy of
      solifenacin by patient-reported OAB duration. METHODS: : In this post hoc
      analysis, patients from a 12-week, open-label study of solifenacin were grouped
      into 3 OAB duration categories: 3 months to 1 year, 1 to 5 years, and more than 5
      years. Changes from baseline to end point on the Patient Perception of Bladder
      Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), and visual analog
      scale (VAS) are summarized for each duration cohort. In addition, analysis of
      covariance was used to compare baseline characteristics and treatment-related
      changes from baseline among the 3 duration cohorts. RESULTS: : After 12 weeks,
      all 3 duration cohorts showed numeric improvements in the PPBC, VAS, and OAB-q.
      Approximately 75% of patients in each group showed improvement on the PPBC. All 3
      cohorts showed a 36- to 45-point improvement in the level of bother on the
      symptom-specific VAS. The magnitude of score improvements (14-31 points) on the
      OAB-q exceeded the minimally important within group difference of 10 points in
      all 3 groups. Although results from the analysis of covariance model indicated
      statistically significant differences between the 3 cohorts for some end points,
      these differences were numerically small and may not be clinically relevant.
      Tolerability was similar among the cohorts and compared with the safety
      population. The most frequently reported adverse events were dry mouth,
      constipation, headache, and blurred vision. CONCLUSIONS: : These findings showed
      that irrespective of OAB symptom duration, patients who received 12 weeks of
      solifenacin perceived meaningful improvements in symptom-specific bother, health
      related quality of life, and their overall bladder condition.

PMID- 22453615
TI  - Uroflow measurements in healthy female volunteers.
AB  - OBJECTIVE: : There is not currently a standard definition of "normal" for
      uroflowmetry parameters, particularly with respect to spontaneous voids or
      multiple repeated measurements within an individual. Our study aimed to describe
      uroflow parameters for "normal" in a group of healthy women based on repeated
      measurements. METHODS: : Spontaneous voids of twelve healthy women were recorded
      over two weeks. Additionally, one prompted void per subject was recorded.
      Prompted voids were compared to the subjects' spontaneous voids. These voids were
      also compared to those of patients evaluated for urinary incontinence. Groups
      were compared using paired t tests. RESULTS: : The mean voided volume was 306 ml
      and the mean maximum flow rate was 49 ml/s. The prompted voids were lower in
      volume, maximum flow, and duration than spontaneous voids. When corrected for
      volume, these differences were not significant. Maximum flow rates in patients
      evaluated for urinary incontinence were lower than those of volunteers.
      CONCLUSIONS: : Uroflowmetry parameters vary widely between and within healthy
      volunteers. Prompted voids are representative of spontaneous voids. Maximum flow
      rates of patients evaluated for urinary incontinence were lower than those of
      volunteers. In a group of healthy volunteers voiding in a private, spontaneous
      setting, a maximum flow rate of lower than 17 ml/s (2 SDs below the mean) might
      be considered abnormally low.

PMID- 22453616
TI  - Association between obesity, sexual activity and sexual function in women with
      pelvic floor disorders.
AB  - OBJECTIVES: : The objective of this study was to determine the association
      between obesity, sexual activity and sexual function in women with pelvic floor
      disorders (PFDs). METHODS: : A retrospective study of women seeking care for PFDs
      was conducted between May 2008 and May 2009. Obesity was defined as body mass
      index >= 30 kg/m. Outcomes included sexual activity and sexual function measured
      using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12
      (PISQ-12). Multivariable regression was used to estimate the association between
      obesity and sexual inactivity and function. RESULTS: : There were 161 (45.5%) non
      obese and 193 (54.5%) obese women, with a subset of 214 sexually active women.
      Obesity was not associated with sexual inactivity, but was associated with worse
      PISQ-12 scores compared with non-obese women (mean score 36.9 +/- 38 versus 74.8
      +/- 34, P < 0.001). On multivariable linear regression, obese women had a mean
      score of 30 points lower (95% confidence interval -40.6 to -20.2, P < 0.001) on
      the PISQ-12 compared with non-obese women. CONCLUSIONS: : Obesity is associated
      with worse sexual function in women with PFDs.

PMID- 22453617
TI  - Society of gynecologic surgeons' survey: mesh use in vaginal prolapse surgery.
AB  - OBJECTIVE: : To evaluate the practice patterns of the Society of Gynecologic
      Surgeons (SGS) members and guests regarding the use of synthetic mesh in vaginal
      prolapse repair. METHODS: : A 26-item questionnaire regarding synthetic mesh use
      in vaginal prolapse repair was placed on the desks of those SGS attendees present
      at the fourth scientific session of the 2008 annual scientific meeting. Voluntary
      participation was requested and the survey questionnaires were retrieved at the
      session's conclusion. Descriptive statistics and cross-tabulation using chi tests
      were performed with SPSS. RESULTS: : One hundred twenty-eight of the 180
      scientific session attendees completed the surveys. Sixty-nine percent (88/128)
      of the respondents identified themselves as urogynecologists and 45% (83/128)
      were male. Forty-five percent (58/128) were SGS members. Sixty-six percent
      (84/128) described their practice setting as academic, 28% (36/128) as community
      based, and 6% (8/128) as other. The majority of the urogynecologists, 65%
      (64/88), used mesh at the time of survey completion versus 40% (8/18) of the
      obstetrician/gynecologists (P < 0.001). Fifty-nine percent (74/125) respondents
      were currently using mesh and 11% (14/125) reported using mesh at one time. Fifty
      six percent (48/86) used mesh in both primary and recurrent repairs. For anterior
      repair, 97% (82/86) used mesh; of these, 31% (26/86) used only mesh kits, 33%
      (28/86) used only free mesh and 33% (28/86) reported using both. For posterior
      repair, 70% (62/88) used mesh; of these 18% (16/88) used only mesh kits, 26%
      (23/88) used only free mesh and 26% (23/88) used both. For anterior repair, 84%
      (71/85) dissected full-thickness and 43% (35/85) plicated connective tissue prior
      to inserting the mesh. The respondents had excised mesh for indications
      including: persistent drainage (59%), persistent pain (21%), hispareunia (21%),
      dyspareunia (16%), and asymptomatic exposure (11%). Fifty percent (44/88)
      initially managed mesh erosion with estrogen cream whereas 29% (26/88) started
      with mesh excision. CONCLUSIONS: : This survey suggests that the majority of
      urogynecologists attending the 34th SGS annual scientific meeting have used
      vaginal mesh for prolapse repair, and they more commonly used it in the anterior
      as compared to the posterior compartment. This has occurred in the absence of
      prospective, controlled, high-quality studies supporting its efficacy and safety.
      Research is clearly needed in this area.

PMID- 22453619
TI  - Risk factors for perineal lacerations in teen deliveries.
AB  - OBJECTIVES: : Severe perineal lacerations have been associated with the
      development of fecal incontinence. This study was designed to identify risk
      factors for severe perineal lacerations in vaginal delivery in a teen population.
      METHODS: : This was a retrospective database analysis of 534 teen term,
      singleton, cephalic vaginal deliveries. The primary outcome was the occurrence of
      a third- or fourth-degree laceration. Categorical and continuous variables were
      compared using the chi and Student t tests, respectively. RESULTS: : Overall, 43
      (8.1%) of our patients had third- or fourth-degree lacerations. In a multivariate
      regression model, the use of insulin in pregnancy, episiotomy, operative vaginal
      delivery, and increased infant birth weight all had an increased odds ratio for
      severe perineal laceration. CONCLUSIONS: : Operative vaginal delivery,
      episiotomy, increased infant birth weight and gestational diabetes requiring
      insulin for glucose control all appear to increase the risk of severe perineal
      laceration at the time of vaginal delivery in a teenage population.

PMID- 22453618
TI  - A retrospective multicenter study on outcomes after midurethral polypropylene
      sling revision for voiding dysfunction.
AB  - OBJECTIVES: : The purpose of this study was to determine outcomes of sling
      revision after midurethral sling (MUS) placement and whether timing of sling
      revision affected those outcomes. MATERIALS AND METHODS: : This is a multicenter
      study including patients who underwent MUS placement and subsequent sling
      revision secondary to voiding dysfunction. Diagnostic outcomes before and after
      sling revision were compared for all sling revision patients with complete data.
      Logistic regression analyses were performed to determine if revision timing
      predicted voiding dysfunction and stress incontinence. RESULTS: : One hundred
      seventy-five patients who met the study criteria had complete data. Overall, 70%
      (133) of MUS were retropubic and 30% (56) were obturator slings. Midurethral
      sling revision was accomplished by cutting (54%), excision (29%), and pulling
      down on the mesh (18%). Stress urinary incontinence (SUI) resolved in 38%,
      urinary tract infections (UTIs) in 69%, and overactive bladder (OAB) in 75%. In
      comparison, 21% experienced de novo SUI; 18%, de novo UTIs; and 12%, de novo OAB
      symptoms after revision. Voiding dysfunction resolved in 80%, however 10%
      experienced new voiding dysfunction symptoms. Retropubic slings displayed more
      voiding dysfunction, higher de novo/worsened OAB, and more UTIs after revision
      than obturator slings. Sling revision timing did not predict persistent voiding
      dysfunction but did predict SUI with earlier revision (<=2 weeks) resulting in
      less postrevision SUI when compared to revisions at 15-90 days or greater than 90
      days. The method of sling revision (cut, excised, pulled down) did not predict
      SUI, OAB, or obstructive voiding symptoms. CONCLUSIONS: : Sling revision resolves
      voiding dysfunction symptoms, UTIs and post-sling OAB symptoms in the majority of
      patients. Resolution of voiding dysfunction is independent of method and timing
      of revision; however earlier revision is associated with decreased postrevision
      SUI.

PMID- 22453620
TI  - The association between post-void leakage and coital incontinence and intrinsic
      sphincter deficiency among women with urinary incontinence.
AB  - OBJECTIVE: : To identify whether an association exists between post-void urinary
      leakage and/or coital incontinence and the diagnosis of intrinsic sphincter
      deficiency (ISD) among women with urinary incontinence. METHODS: : Ninety women
      presenting to a tertiary urogynecology office with complaints of urinary
      incontinence were included in this retrospective chart review. All patients
      underwent a complete history and physical examination, including direct
      questioning about the symptoms of post-void leakage and coital incontinence.
      Multichannel urodynamic testing was evaluated for each patient and ISD was
      defined by a Valsalva leak point pressure of less than or equal to 60 cm H2O
      and/or a maximal urethral closure pressure of less than or equal to 20 cm H2O.
      The prevalence of ISD among those patients with post-void leakage and/or coital
      incontinence was evaluated. RESULTS: : The prevalence of ISD among the study
      population was 64%. Intrinsic sphincter deficiency was diagnosed in 45/62
      patients with post-void leakage and in 13/28 patients without post-void leakage
      (72.6% and 46.4%, respectively, P = 0.0311). Intrinsic sphincter deficiency was
      present in 21/24 patients with coital incontinence and 37/66 patients without
      coital incontinence (87.5% and 56.1%, respectively, P = 0.0061). Patients with
      both symptoms were diagnosed with ISD 90% of the time, while only 41.7% of
      patients with neither symptom had ISD (P = 0.0014, sensitivity = 64.5%). Patients
      with either symptom were diagnosed with ISD 72.7% of the time, compared to 41.7%
      of patients with neither symptom (P = 0.0117, sensitivity = 82.8%). The positive
      predictive value for coital incontinence alone and ISD was 87.5%, and for both
      symptoms was 90%. CONCLUSIONS: : The symptoms of post-void leakage and coital
      incontinence are associated with ISD. The strong positive predictive value of
      both symptoms with ISD should encourage physicians to include direct questioning
      about these symptoms during the history taking and treatment planning for women
      with urinary incontinence.

PMID- 22453621
TI  - Does tension-free vaginal tape placement at the time of total prolift colpopexy
      affect distal anterior vaginal support?
AB  - OBJECTIVES: : Pelvic organ prolapse (POP) and stress urinary incontinence often
      require concomitant procedures to treat both conditions. The purpose of this
      study was to determine whether tension-free vaginal tape (TVT) at the time of
      total Prolift colpopexy (TPC) affected distal anterior vaginal wall support.
      METHODS: : This was a retrospective cohort study of women that had TPC (n = 62)
      between January 2005 and December 2007. All patients had no uterus and underwent
      TPC with mesh placement in the anterior and posterior vaginal compartments. A
      concomitant TVT was placed only in those who had a preoperative diagnosis of
      urodynamic stress urinary incontinence with prolapse reduction. Patients were
      subdivided into those with (n = 26) and without TVT (n = 36). Data were compared
      between groups using Student t, Wilcoxon rank sum, and Fisher exact tests (P <=
      0.05). RESULTS: : There were no significant differences between groups for all
      preoperative variables. Patients were observed for 6 to 12 months after TPC.
      Postoperatively, those with and without TVT had similar anterior POP
      quantification measurements (points Aa and Ba; P > 0.05), although the group with
      TVT had significantly more patients with anterior stage 2 and 3 recurrences (23%)
      when compared with the group without TVT (5%, P = 0.04). CONCLUSIONS: : Tension
      free vaginal tape does not provide additional distal anterior vaginal wall
      support for patients undergoing TPC.

PMID- 22453622
TI  - Does body mass index impact passing voiding trial after midurethral sling
      procedures for stress urinary incontinence?
AB  - OBJECTIVE: : To test the hypothesis that body mass index (BMI) is a factor
      associated with passing a voiding trial after midurethral sling procedures for
      stress urinary incontinence (SUI). STUDY DESIGN: : The medical records of 136
      consecutive patients who underwent placement of either tension-free vaginal tape
      (TVT) or transobturator tape (TOT) for SUI during a 1-year period (September 1,
      2007 to August 31, 2008) were retrospectively reviewed. Variables assessed were
      BMI, age, and passing or failing a postoperative urinary voiding trial. Patients
      with concomitant pelvic organ prolapse surgeries were not included in this
      analysis. RESULTS: : Sixty-seven patients underwent TVT, whereas 69 had TOT
      procedures. In the TVT group, 30 patients (42%) were unable to void immediately
      postoperatively compared with 11 patients (16%) in the TOT group (P = 0.0003).
      The mean (SD) age and BMI of patients who failed or passed voiding trials was
      58.6 (12.0) years and 28.0 (4.9) kg/m or 53.5 (12.3) years and 29.8 (5.7) kg/m,
      respectively. Of 38 patients who did not pass a voiding trial on the day of the
      procedure, 31 (82%) passed on postoperative day 1, and all patients had passed a
      voiding trial by postoperative day 11. The mean (SD) BMI for 7 patients who did
      not pass voiding trial by postoperative day 1 was 28.3 (5.2) kg/m. CONCLUSIONS: :
      Women with higher BMIs were more likely to pass voiding trials after midurethral
      sling procedures. Patients who had TOT placement had greater success passing a
      postprocedure voiding trial than did patients who had TVT placement.

PMID- 22453623
TI  - Sacral Neuromodulator InterStim Surgical Site Infection: Two Case Reports.
AB  - OBJECTIVE: : The surgical site infection rate of sacral neuromodulator placement
      for the treatment of refractory urge urinary incontinence is reported to be
      between 5% and 7.9%. Our objective was to report the investigation process of
      these infections and a possible source for their occurrence. METHODS: : We
      performed infection control surveillance of two patients that underwent sacral
      neuromodulator placement on the same date, in the same operating room, and by the
      same staff who developed similar sacral cellulitis postoperatively. RESULTS: :
      The investigation revealed Staphylococcus aureus infections with a common
      antibiogram in both patients. Nasal cultures of all personnel involved in their
      care, showed Staphylococcus aureus with the same antibiogram only in a Medtronic
      representative who had manipulated the InterStim settings. Genetic analysis
      showed this to be an identical strain in one patient infection. CONCLUSIONS: :
      The postoperative manipulation of device settings may be a source of surgical
      site infection, and infection control practices including strict hand washing,
      gloves, gown and mask may be warranted.

PMID- 22453624
TI  - Hemorrhagic complication during placement of tension-free vaginal tape.
AB  - A 66-year-old para III with a 20-year history of stress urinary incontinence
      underwent placement of tension-free vaginal tape. Intraoperative arterial
      bleeding occurred. An expanding hematoma was palpated postoperatively.
      Interventional radiology performed a pelvic arteriogram with selective bilateral
      internal iliac arteriograms, a supraselective anterior division and obturator
      arteriogram, a left external iliac arteriogram, coil embolization of a branch of
      the left obturator artery, and gel foam embolization of the anterior division of
      the left internal iliac artery.

PMID- 22453625
TI  - Botulinum toxin type A injection, followed by home-based functional training for
      upper limb hemiparesis after stroke.
AB  - Botulinum toxin type A (BoNT-A) has been reported to be an effective treatment
      for limb spasticity after stroke. However, the reduction in the spasticity after
      BoNT-A injection alone does not ensure an improvement in the active motor
      function of the affected limb. The aim of this study was to clarify the clinical
      effects of a BoNT-A injection, followed by home-based functional training on not
      only the passive but also the active motor function of the affected spastic upper
      limb in poststroke hemiparetic patients. Eighty poststroke patients with spastic
      upper limb hemiparesis were studied. The severity of hemiparesis was categorized
      as Brunnstrom stage of 3 for hand-fingers in all patients. BoNT-A (maximum dose
      of 240 U) was injected into the target muscles of the affected upper limb after a
      clinical evaluation using the modified Ashworth scale, range of motion, Fugl
      Meyer Assessment, and the Wolf Motor Function Test. Following the injection,
      occupational therapists provided home-based functional training for each patient
      on a one-to-one basis. The follow-up evaluation was performed 4 weeks after the
      injection. A significant improvement was found in the modified Ashworth scale and
      range of motion. The changes in the Fugl-Meyer Assessment and the Wolf Motor
      Function Test indicated a significant improvement in the active motor function of
      the affected upper limb. In conclusions, our proposed protocol of a BoNT-A
      injection, followed by home-based functional training seems to have the potential
      to improve the active motor function of the affected upper limb after stroke,
      although the efficacy should be confirmed in a randomized-controlled trial.

PMID- 22453626
TI  - Representations of the Americans with Disabilities Act employment-related issues
      in the Wall Street Journal (1990-2008):  a feasibility study.
AB  - This feasibility study examines the coverage of employment-related issues related
      to people with disabilities in the Americans with Disabilities Act of 1990. The
      study is a first in a series of future studies focusing on disability issues in
      the international economic media. A survey of 39 newspaper articles published in
      the Wall Street Journal, a leading and most circulated business newspaper in the
      USA. Specifically, it comprised articles taken from three periods: 1990, the year
      the Americans with Disabilities Act was enacted; 2000, a decade later; and 2008,
      the year the amendments were revised with respect to definitions and employment.
      Data were analyzed by quantitative and qualitative content analysis. The results
      suggest a mixed representation: a decline in negative representations of
      disability throughout the years alongside the emergence of a legal-fiscal
      discourse of a disability that depicts persons with disabilities as a fiscal
      burden on employers. It seems that the new image of disability presents
      conflicting interests between the mission of the law, promoting employers' hiring
      of people with disabilities, and the economic realities of accommodating them at
      the workplace. Additional research is needed to examine whether this image is
      unique to the economic media or may reflect a concern in the business community.

PMID- 22453627
TI  - The role of assistive technology in self-perceived participation.
AB  - The aim of this study was to develop an understanding of how assistive technology
      (AT) contributes to self-perceived participation for individuals with spinal cord
      injuries and to propose a revised definition of AT in light of the findings. A
      grounded theory study of 19 adults with spinal cord injuries was conducted.
      Participants engaged in individual in-depth interviews and took photographs of
      the role of AT in their own environments. Analysis consisted of an inductive
      process of constant comparison. Participants attended a follow-up focus group
      intended to verify and contribute to the credibility of the findings. The primary
      theme identified was AT as a means to participation. Three categories served to
      identify the decision-making processes that individuals underwent to select AT
      that would promote positive participation experiences: inclusion versus autonomy
      and accomplishment, availability and cost and contexts of use. A new definition
      of AT was proposed; this definition identifies AT as a means to enable
      occupation, emphasizes the relevance of the environment and highlights the
      importance placed on self-perceived participation. AT recommendations must be
      based on a thorough understanding of the role that AT plays in the lives of
      clients. Future research will further develop and validate the definition
      proposed in this study.

PMID- 22453629
TI  - Prevention of acute/severe hypoglycemia-induced neuron death by lactate
      administration.
AB  - Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who
      attempt tight control of blood glucose and may lead to cognitive dysfunction.
      Accumulating evidence from animal models suggests that hypoglycemia-induced
      neuronal death is not a simple result of glucose deprivation, but is instead the
      end result of a multifactorial process. In particular, the excessive activation
      of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide
      adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we
      investigate whether lactate administration in the absence of cytosolic NAD(+)
      affords neuroprotection against hypoglycemia-induced neuronal death.
      Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and
      blood lactate concentration after hypoglycemia. Lactate administered without
      glucose was not sufficient to promote electroencephalogram recovery from an
      isoelectric state during hypoglycemia. However, supplementation of glucose with
      lactate reduced neuronal death by ~80% in the hippocampus. Hypoglycemia-induced
      superoxide production and microglia activation was also substantially reduced by
      administration of lactate. Taken together, these results suggest an intriguing
      possibility: that increasing brain lactate following hypoglycemia offsets the
      decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative
      energy substrate that can effectively bypass glycolysis and be fed directly to
      the citric acid cycle to maintain cellular ATP levels.

PMID- 22453628
TI  - Novel mitochondrial targets for neuroprotection.
AB  - Mitochondrial dysfunction contributes to the pathophysiology of acute neurologic
      disorders and neurodegenerative diseases. Bioenergetic failure is the primary
      cause of acute neuronal necrosis, and involves excitotoxicity-associated
      mitochondrial Ca(2+) overload, resulting in opening of the inner membrane
      permeability transition pore and inhibition of oxidative phosphorylation.
      Mitochondrial energy metabolism is also very sensitive to inhibition by reactive
      O(2) and nitrogen species, which modify many mitochondrial proteins, lipids, and
      DNA/RNA, thus impairing energy transduction and exacerbating free radical
      production. Oxidative stress and Ca(2+)-activated calpain protease activities
      also promote apoptosis and other forms of programmed cell death, primarily
      through modification of proteins and lipids present at the outer membrane,
      causing release of proapoptotic mitochondrial proteins, which initiate caspase
      dependent and caspase-independent forms of cell death. This review focuses on
      three classifications of mitochondrial targets for neuroprotection. The first is
      mitochondrial quality control, maintained by the dynamic processes of
      mitochondrial fission and fusion and autophagy of abnormal mitochondria. The
      second includes targets amenable to ischemic preconditioning, e.g., electron
      transport chain components, ion channels, uncoupling proteins, and mitochondrial
      biogenesis. The third includes mitochondrial proteins and other molecules that
      defend against oxidative stress. Each class of targets exhibits excellent
      potential for translation to clinical neuroprotection.

PMID- 22453630
TI  - Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized (13)C magnetic
      resonance spectroscopic imaging.
AB  - The branched chain amino acid transaminase (BCAT) has an important role in
      nitrogen shuttling and glutamate metabolism in the brain. The purpose of this
      study was to describe the cerebral distribution and metabolism of hyperpolarized
      2-keto[1-(13)C]isocaproate (KIC) in the normal rat using magnetic resonance
      modalities. Hyperpolarized KIC is metabolized to [1-(13)C]leucine (leucine) by
      BCAT. The results show that KIC and its metabolic product, leucine, are present
      at imageable quantities 20 seconds after end of KIC administration throughout the
      brain. Further, significantly higher metabolism was observed in hippocampal
      regions compared with the muscle tissue. In conclusion, the cerebral metabolism
      of hyperpolarized KIC is imaged and hyperpolarized KIC may be a promising
      substrate for evaluation of cerebral BCAT activity in conjunction with
      neurodegenerative disease.

PMID- 22453631
TI  - Enhanced neuronal excitability in adult rat brainstem causes widespread
      repetitive brainstem depolarizations with cardiovascular consequences.
AB  - The brainstem of the adult rat is relatively resistant to spreading
      depolarization (SD) but after enhancement of excitability SD can be evoked by
      local application of KCl. In the present experiments, we observed that the
      enhanced excitability even triggers prolonged periods of repetitive
      depolarizations (RDs), which elicit significant cardiovascular changes. In
      contrast to KCl-evoked SDs with amplitudes of ~24 mV and spreading velocity of 4
      mm/min, spontaneous RDs had amplitudes of 7 to 12 mV, propagated up to 30 times
      faster than KCl-evoked SDs, and depolarized larger brainstem areas including the
      contralateral side. Similarly as SD, RDs depended on glutamatergic
      neurotransmission and were blocked by MK-801 or by the calcium channel blocker
      agatoxin. They depended on sodium channels and were blocked by tetrodotoxin.
      Functionally, the invasion of RDs into the spinal trigeminal and other nuclei
      evoked bursts of action potentials, indicating that specific neuronal systems are
      affected. In fact, during episodes of RDs the blood pressure and the local blood
      flow at the surface of the brainstem and the cortex increased substantially.
      Brainstem RDs did not propagate into the cerebral cortex. We propose to consider
      brainstem RPs as a pathophysiological mechanism whose significance for brainstem
      disease states should be further explored.

PMID- 22453634
TI  - Effective detection for linear up-sampling by factor of fraction.
AB  - In this study, we propose an effective method for detecting linear up-sampling in
      images. Our method includes three parts. First, we present an algorithm
      Resampling Matrix Construction (RMC) that automatically derives the resampling
      matrix for any given resampling factor of fraction. Second, we show an algorithm
      Zeroing Mask Derivation (ZMD) that constructs a zeroing mask for the resampling
      by produced by the proposed algorithm. Lastly, we propose an algorithm Up
      sampling Detection (UD) that detects the up-sampling in images using the zeroing
      masks in a specific order. Compared with existing methods, the proposed method
      for up-sampling detection can not only effectively detect resampling by any
      fraction but can also recover the up-sampling fraction. Preliminary experimental
      results show that the proposed method is indeed effective. 

PMID- 22453632
TI  - TTC7B emerges as a novel risk factor for ischemic stroke through the convergence
      of several genome-wide approaches.
AB  - We hereby propose a novel approach to the identification of ischemic stroke (IS)
      susceptibility genes that involves converging data from several unbiased genetic
      and genomic tools. We tested the association between IS and genes differentially
      expressed between cases and controls, then determined which data mapped to
      previously reported linkage peaks and were nominally associated with stroke in
      published genome-wide association studies. We first performed gene expression
      profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls.
      Sixteen differentially expressed genes mapped to reported whole-genome linkage
      peaks, including the TTC7B gene, which has been associated with major
      cardiovascular disease. At the TTC7B locus, 46 tagging polymorphisms were tested
      for association in 565 Portuguese IS cases and 520 controls. Markers nominally
      associated in at least one test and defining associated haplotypes were then
      examined in 570 IS Spanish cases and 390 controls. Several polymorphisms and
      haplotypes in the intron 5-intron 6 region of TTC7B were also associated with IS
      risk in the Spanish and combined data sets. Multiple independent lines of
      evidence therefore support the role of TTC7B in stroke susceptibility, but
      further work is warranted to identify the exact risk variant and its pathogenic
      potential.

PMID- 22453635
TI  - Blind image quality assessment: a natural scene statistics approach in the DCT
      domain.
AB  - We develop an efficient, general-purpose, blind/noreference image quality
      assessment (NR-IQA) algorithm using a natural scene statistics (NSS) model of
      discrete cosine transform (DCT) coefficients. The algorithm is computationally
      appealing, given the availability of platforms optimized for DCT computation. The
      approach relies on a simple Bayesian inference model to predict image quality
      scores given certain extracted features. The features are based on an NSS model
      of the image DCT coefficients. The estimated parameters of the model are utilized
      to form features that are indicative of perceptual quality. These features are
      used in a simple Bayesian inference approach to predict quality scores. The
      resulting algorithm, which we name BLIINDS-II, requires minimal training and
      adopts a simple probabilistic model for score prediction. Given the extracted
      features from a test image, the quality score that maximizes the probability of
      the empirically determined inference model is chosen as the predicted quality
      score of that image. When tested on the LIVE IQA database, BLIINDS-II is shown to
      correlate highly with human judgments of quality, at a level that is competitive
      with the popular SSIM index.

PMID- 22453636
TI  - Robust reversible watermarking via clustering and enhanced pixel-wise masking.
AB  - Robust reversible watermarking (RRW) methods are popular in multimedia for
      protecting copyright, while preserving intactness of host images and providing
      robustness against unintentional attacks. However, conventional RRW methods are
      not readily applicable in practice. That is mainly because 1) they fail to offer
      satisfactory reversibility on large-scale image datasets; 2) they have limited
      robustness in extracting watermarks from the watermarked images destroyed by
      different unintentional attacks; and 3) some of them suffer from extremely poor
      invisibility for watermarked images. Therefore, it is necessary to have a
      framework to address these three problems, and further improve its performance.
      This paper presents a novel pragmatic framework, wavelet-domain statistical
      quantity histogram shifting and clustering (WSQH-SC). Compared with conventional
      methods, WSQH-SC ingeniously constructs new watermark embedding and extraction
      procedures by histogram shifting and clustering, which are important for
      improving robustness and reducing run-time complexity. Additionally, WSQH-SC
      includes the property inspired pixel adjustment (PIPA) to effectively handle
      overflow and underflow of pixels. This results in satisfactory reversibility and
      invisibility. Furthermore, to increase its practical applicability, WSQH-SC
      designs an enhanced pixel-wise masking (EPWM) to balance robustness and
      invisibility. We perform extensive experiments over natural, medical, and
      synthetic aperture radar (SAR) images to show the effectiveness of WSQH-SC by
      comparing with the histogram rotation (HR)-based and histogram distribution
      constrained (HDC) methods. 

PMID- 22453637
TI  - Robust interactive image segmentation using convex active contours.
AB  - The state-of-the-art interactive image segmentation algorithms are sensitive to
      the user inputs and often unable to produce an accurate boundary with a small
      amount of user interaction. They frequently rely on laborious user editing to
      refine the segmentation boundary. In this paper, we propose a robust and accurate
      interactive method based on the recently developed continuous-domain convex
      active contour model. The proposed method exhibits many desirable properties of
      an effective interactive image segmentation algorithm, including robustness to
      user inputs and different initializations, the ability to produce a smooth and
      accurate boundary contour, and the ability to handle topology changes.
      Experimental results on a benchmark data set show that the proposed tool is
      highly effective and outperforms the state-of-the-art interactive image
      segmentation algorithms. 

PMID- 22453638
TI  - Network-based H.264/AVC whole frame loss visibility model and frame dropping
      methods.
AB  - We examine the visual effect of whole frame loss by different decoders. Whole
      frame losses are introduced in H.264/AVC compressed videos which are then decoded
      by two different decoders with different common concealment effects: frame copy
      and frame interpolation. The videos are seen by human observers who respond to
      each glitch they spot. We found that about 39% of whole frame losses of B frames
      are not observed by any of the subjects, and over 58% of the B frame losses are
      observed by 20% or fewer of the subjects. Using simple predictive features which
      can be calculated inside a network node with no access to the original video and
      no pixel level reconstruction of the frame, we developed models which can predict
      the visibility of whole B frame losses. The models are then used in a router to
      predict the visual impact of a frame loss and perform intelligent frame dropping
      to relieve network congestion. Dropping frames based on their visual scores
      proves superior to random dropping of B frames. 

PMID- 22453639
TI  - Rate-distortion optimised video transmission using pyramid vector quantisation.
AB  - Conventional video compression relies on interframe prediction (motion
      estimation), intra frame prediction and variable-length entropy encoding to
      achieve high compression ratios but, as a consequence, produces an encoded
      bitstream that is inherently sensitive to channel errors. In order to ensure
      reliable delivery over lossy channels, it is necessary to invoke various
      additional error detection and correction methods. In contrast, techniques such
      as Pyramid Vector Quantisation have the ability to prevent error propagation
      through the use of fixed length codewords. This paper introduces an efficient
      rate distortion optimisation algorithm for intra-mode PVQ which offers similar
      compression performance to intra H.264/AVC and Motion JPEG 2000 while offering
      inherent error resilience. The performance of our enhanced codec is evaluated for
      HD content in the context of a realistic (IEEE 802.11n) wireless environment. We
      show that PVQ provides high tolerance to corrupted data compared to the state of
      the art while obviating the need for complex encoding tools. 

PMID- 22453640
TI  - Depth sensation enhancement using the just noticeable depth difference.
AB  - In this paper, we present a novel depth sensation enhancement algorithm
      considering the behavior of human visual system (HVS) toward stereoscopic image
      displays. On the basis of the recent studies on the just noticeable depth
      difference (JNDD), which represents a threshold that a human can perceive the
      depth difference between objects, we modify the depth image such that neighboring
      objects in the depth image can have a depth value difference of at least the
      JNDD. This modification is modeled via an energy minimization framework using
      three energy terms defined as depth data preservation, depth-order preservation,
      and depth difference expansion. The depth data term enforces minimal changes in
      the depth image with an additional weighting function that controls the direction
      of depth changes. The depth-order term restricts the inversion of the local and
      global depth orders among objects, and the JNDD term leads to an increase in the
      depth differences between segments. Throughout subjective quality evaluation on a
      stereoscopic image display, it is demonstrated that the human depth sensation is
      effectively improved by the proposed algorithm. 

PMID- 22453641
TI  - Modeling the interaction of seven bisphosphonates with the hydroxyapatite(100)
      face.
AB  - The interaction of seven pamidronate bisphosphonate (Pami-BPs) and its analogs
      with the hydroxyapatite (HAP) (100) surface was studied using density functional
      theory (DFT) and molecular dynamic (MD) methods. Partial Mulliken oxygen atomic
      charges in protonated structures were calculated at the level of B3LYP/6-31G*.
      The MD simulation was performed using the Discover module of Material Studio by
      compass force field. The results indicate the abilities of donating electrons of
      the oxygen atoms of the phosphate groups that are closely associated with the
      antiresorptive potency. The binding energies, including vdw and electrostatic,
      are used to discuss the mechanism of antiresorption. The results of calculations
      show that the strength of interaction of the HAP (100) face with the
      bisphosphonates is N(4) > N(6) > N(7) > N(5) > N(3) > N(2) > N(1) according to
      their experimental pIC(50) values.

PMID- 22453642
TI  - Weighted average prediction for improving consensus performance of second-order
      delayed multi-agent systems.
AB  - In this paper, the weighted average prediction (WAP) is introduced into the
      existing consensus protocol for simultaneously improving the robustness to
      communication delay and the convergence speed of achieving the consensus. The
      frequency-domain analysis and algebra graph theory are employed to derive the
      necessary and sufficient condition guaranteeing the second-order delayed multi
      agent systems applying the WAP-based consensus protocol to achieve the stationary
      consensus. It is proved that introducing the WAP with the proper length into the
      existing consensus protocol can improve the robustness against communication
      delay. Also, we prove that for two kinds of second-order delayed multi-agent
      systems: 1) the IR-ones with communication delay approaching zero and 2) the ones
      with communication delay approaching the maximum delay, introducing the WAP with
      the proper length into the existing consensus protocol can accelerate the
      convergence speed of achieving the stationary consensus.

PMID- 22453643
TI  - Link technologies and BlackBerry mobile health (mHealth) solutions: a review.
AB  - The number of wearable wireless sensors is expected to grow to 400 million by the
      year 2014, while the number of operational mobile subscribers has already passed
      the 5.2 billion mark in 2011. This growth results in an increasing number of
      mobile applications including: Machine-to-Machine (M2M) communications,
      Electronic-Health (eHealth), and Mobile-Health (mHealth). A number of emerging
      mobile applications that require 3G and 4G mobile networks for data transport
      relate to telemedicine, including establishing, maintaining, and transmitting
      health-related information, research, education, and training. This review paper
      takes a closer look at these applications, specifically with regard to the
      healthcare industry and their underlying link technologies. The authors believe
      that the BlackBerry platform and the associated infrastructure (i.e., BlackBerry
      Enterprise Server) is a logical and practical solution for eHealth, mHealth,
      sensor and M2M deployments, which are considered in this paper.

PMID- 22453644
TI  - An integrated healthcare information system for end-to-end standardized exchange
      and homogeneous management of digital ECG formats.
AB  - This paper investigates the application of the enterprise information system
      (EIS) paradigm to standardized cardiovascular condition monitoring. There are
      many specifications in cardiology, particularly in the ECG standardization arena.
      The existence of ECG formats, however, does not guarantee the implementation of
      homogeneous, standardized solutions for ECG management. In fact, hospital
      management services need to cope with various ECG formats and, moreover, several
      different visualization applications. This heterogeneity hampers the
      normalization of integrated, standardized healthcare information systems, hence
      the need for finding an appropriate combination of ECG formats and a suitable EIS
      based software architecture that enables standardized exchange and homogeneous
      management of ECG formats. Determining such a combination is one objective of
      this paper. The second aim is to design and develop the integrated healthcare
      information system that satisfies the requirements posed by the previous
      determination. The ECG formats selected include ISO/IEEE11073, Standard
      Communications Protocol for Computer-Assisted Electrocardiography, and an ECG
      ontology. The EIS-enabling techniques and technologies selected include web
      services, simple object access protocol, extensible markup language, or business
      process execution language. Such a selection ensures the standardized exchange of
      ECGs within, or across, healthcare information systems while providing modularity
      and accessibility.

PMID- 22453645
TI  - Translation and validation of the Dutch version of the Effective Consumer Scale
      (EC-17).
AB  - PURPOSE: The Effective Consumer Scale (EC-17) measures the skills of
      musculoskeletal patients in managing their own healthcare. The objectives of this
      study were to translate the EC-17 into Dutch and to further evaluate its
      psychometric properties. METHODS: The EC-17 was translated and cognitively
      pretested following cross-cultural adaptation guidelines. Two hundred and thirty
      eight outpatients (52 % response rate) with osteoarthritis or fibromyalgia
      completed the EC-17 along with other validated measures. Three weeks later, 101
      patients completed the EC-17 again. RESULTS: Confirmatory factor analysis
      supported the unidimensional structure of the scale. The items adequately fit the
      Rasch model and only one item demonstrated differential item functioning. Person
      reliability was high (0.92), but item difficulty levels tended to cluster around
      the middle of the scale, and measurement precision was highest for moderate and
      lower levels of skills. The scale demonstrated adequate test-retest reliability
      (ICC = 0.71), and correlations with other measures were largely as expected.
      CONCLUSION: The results supported the validity and reliability of the Dutch
      version of the EC-17, but suggest that the scale is best targeted at patients
      with relatively low levels of skills. Future studies should further examine its
      sensitivity to change in a clinical trial specifically aimed at improving
      effective consumer skills.

PMID- 22453646
TI  - Dendrite-like Co3O4 nanostructure and its applications in sensors,
      supercapacitors and catalysis.
AB  - Dendrite-like Co(3)O(4) nanostructure, made up of many nanorods with diameters of
      15-20 nm and lengths of 2-3 MUm, has been successfully prepared by calcining the
      corresponding nanostructured Co-8-hydroxyquinoline coordination precursor in air.
      The Co(3)O(4) nanostructure was evaluated as an electrochemical sensor for
      H(2)O(2) detection and the results reveal that it has good linear dependence and
      high sensitivity to H(2)O(2) concentration changes. As an electrode material of a
      supercapacitor, it was found that the nanostructured Co(3)O(4) electrode exhibits
      high specific capacitance and long cycle life. The Co(3)O(4) nanostructure also
      has good catalytic properties and is steadily active for CO oxidation, giving
      100% CO conversion at low temperatures. The multifunctional Co(3)O(4)
      nanostructure would be a promising functional nanomaterial applied in multi
      industrialized fields.

PMID- 22453648
TI  - The effects of continuous positive airway pressure therapy withdrawal on cardiac
      repolarization: data from a randomized controlled trial.
AB  - AIMS: The preliminary evidence supports an association between obstructive sleep
      apnoea (OSA), disturbed cardiac repolarization, and consequent cardiac
      dysrhythmias. The aim of the current trial was to assess the effects of
      continuous positive airway pressure (CPAP) therapy withdrawal on the measures of
      cardiac repolarization in patients with OSA. METHODS AND RESULTS: Forty-one OSA
      patients established on CPAP treatment were randomized to either CPAP withdrawal
      (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Polysomnography
      was performed, and indices of cardiac repolarization (QT(c), TpTe(c) intervals)
      and dispersion of repolarization (TpTe/QT ratio) were derived from 12-lead
      electrocardiography (ECG) at baseline and 2 weeks. Continuous positive airway
      pressure withdrawal led to a recurrence of OSA. Compared with therapeutic CPAP,
      subtherapeutic CPAP for 2 weeks was associated with a significant increase in the
      length of the QT(c) and TpTe(c) intervals (mean difference between groups 21.4
      ms, 95% CI 11.3-1.6 ms, P < 0.001 and 14.4 ms, 95% CI 7.2-21.5 ms, P < 0.001,
      respectively) and in the TpTe/QT ratio (mean difference between groups 0.02, 95%
      CI 0.00-0.03, P = 0.020). There was a statistically significant correlation
      between the change in apnoea/hypopnoea index (AHI) from baseline, and both the
      change in the QT(c) interval and the TpTe(c) interval (r = 0.60, 95% CI 0.36
      0.77, P < 0.001 and r = 0.45, 95% CI 0.17-0.67, P = 0.003, n = 41, respectively).
      CONCLUSION: Continuous positive airway pressure withdrawal is associated with the
      prolongation of the QT(c) and TpTe(c) intervals and TpTe/QT ratio, which may
      provide a possible mechanistic link between OSA, cardiac dysrhythmias, and thus
      sudden cardiac death.

PMID- 22453647
TI  - Comparative demography of an epiphytic lichen: support for general life history
      patterns and solutions to common problems in demographic parameter estimation.
AB  - Lichens are major components in many terrestrial ecosystems, yet their population
      ecology is at best only poorly understood. Few studies have fully quantified the
      life history or demographic patterns of any lichen, with particularly little
      attention to epiphytic species. We conducted a 6-year demographic study of
      Vulpicida pinastri, an epiphytic foliose lichen, in south-central Alaska. After
      testing multiple size-structured functions to describe patterns in each V.
      pinastri demographic rate, we used the resulting estimates to construct a
      stochastic demographic model for the species. This model development led us to
      propose solutions to two general problems in construction of demographic models
      for many taxa: how to simply but accurately characterize highly skewed growth
      rates, and how to estimate recruitment rates that are exceptionally difficult to
      directly observe. Our results show that V. pinastri has rapid and variable growth
      and, for small individuals, low and variable survival, but that these traits are
      coupled with considerable longevity (e.g., >50 years mean future life span for a
      4-cm(2) thallus) and little deviation of the stochastic population growth rate
      from the deterministic expectation. Comparisons of the demographic patterns we
      found with those of other lichen studies suggest that their relatively simple
      architecture may allow clearer generalities about growth patterns for lichens
      than for other taxa, and that the expected pattern of faster growth rates for
      epiphytic species is substantiated.

PMID- 22453649
TI  - Thrombotic arch in ST-segment elevation myocardial infarction: comparison between
      two-dimensional and three-dimensional optical frequency domain imaging.

PMID- 22453650
TI  - Arrhythmogenic cardiomyopathy suspected by electrocardiogram: confirmed by
      angiography.

PMID- 22453651
TI  - Right ventricular systolic function for risk stratification in patients with
      stable left ventricular systolic dysfunction: comparison of radionuclide
      angiography to echoDoppler parameters.
AB  - AIMS: Previous studies have demonstrated that the radionuclide right ventricular
      (RV) ejection fraction (RVEF), tricuspid annular plane systolic excursion
      (TAPSE), and tissue Doppler peak systolic tricuspid annular velocity (STr) were
      independent predictors of cardiac survival in stable patients with left
      ventricular systolic dysfunction (LVSD). No study has compared the prognostic
      value of these three RV parameters. The aim of this study was to compare the
      prognostic value of RVEF, TAPSE, and STr in a large group of patients with LVSD.
      METHODS AND RESULTS: We analysed 527 consecutive patients who underwent an
      extensive prognostic evaluation (clinical data, biological data, radionuclide
      angiography, echoDopplercardiography, cardiopulmonary exercise test). Tricuspid
      annular plane systolic excursion and STr were weakly correlated with RVEF (r =
      0.20). During a follow-up period of 1268 days (802-1830), there were 121
      cardiovascular deaths. Best cut-off values were 37%, 9.7 cm/s, and 18.5 mm for
      RVEF, STr, and TAPSE, respectively. Right ventricular ejection fraction was a
      powerful independent predictor of cardiac survival [relative risk (RR): 2.05
      (1.29-3.26), P = 0.002]. Peak systolic tricuspid annular velocity added a modest
      prognostic information [RR: 1.56 (1.02-2.39), P = 0.04]. However, the combination
      of STr with RVEF was the most powerful predictor of cardiovascular death.
      Tricuspid annular plane systolic excursion was not an independent predictor of
      cardiac survival. CONCLUSIONS: Right ventricular systolic function remains a
      powerful independent predictor of the clinical outcome. Even in the context of a
      complete echocardiographic assessment, radionuclide RVEF continues to be the most
      powerful RV systolic parameter for cardiac survival prediction. However, the
      determination of STr, in addition to RVEF, could improve risk stratification.

PMID- 22453652
TI  - Primary sarcoma of pulmonary artery resembling large pulmonary thrombus:
      diagnostic utility of different imaging modalities.

PMID- 22453653
TI  - Intracoronary microparticles and microvascular obstruction in patients with ST
      elevation myocardial infarction undergoing primary percutaneous intervention.
AB  - AIMS: Microparticles (MP) are cell-derived fragments known to be increased in the
      blood of patients with acute coronary syndromes. We aimed to assess, in ST
      elevation myocardial infarction (STEMI), the systemic and local (in the culprit
      coronary artery) levels of platelet-derived MP (PMP, CD42+CD31+) and endothelial
      derived MP (EMP, CD42-CD31+) and their relation to indexes of microvascular
      obstruction (MVO). METHODS AND RESULTS: In 78 STEMI patients undergoing
      successful primary percutaneous coronary intervention, blood samples were
      sequentially drawn from the aorta and the culprit coronary artery for
      cytofluorimetric MP detection. Thrombolysis in myocardial infarction (TIMI) flow,
      thrombus score (TS), corrected TIMI frame count (cTFC), myocardial blush grade
      (MBG), quantitative blush evaluator (QuBE) score, and 90 min ST resolution
      (SigmaSTR) were calculated. Both PMP and EMP levels were significantly higher in
      the intracoronary than in the aortic blood samples. Intracoronary PMP and EMP
      levels were positively related to TS and cTFC and inversely related to MBG and
      QuBE. Aortic PMP (but not EMP) levels were related to TS and cTFC and, inversely,
      to QuBE. Intracoronary PMP were independently related to angiographic and
      electrocardiographic MVO in a multivariate model. CONCLUSION: The correlations of
      intracoronary EMP and of both systemic and intracoronary PMP levels with TS
      support the role of MP as markers of ongoing thrombosis. Moreover, the
      correlation of intracoronary MP with indexes of microvascular dysfunction
      suggests, for the first time, a possible direct role of MP in the pathogenesis of
      MVO.

PMID- 22453654
TI  - Nurse-led care vs. usual care for patients with atrial fibrillation: results of a
      randomized trial of integrated chronic care vs. routine clinical care in
      ambulatory patients with atrial fibrillation.
AB  - AIMS: The management of patients with atrial fibrillation (AF) is often
      inadequate due to deficient adherence to the guidelines. A nurse-led AF clinic
      providing integrated chronic care to improve guideline adherence and activate
      patients in their role, may effectively reduce morbidity and mortality but such
      care has not been tested in a large randomized trial. Therefore, we performed a
      randomized clinical trial to compare the AF clinic with routine clinical care in
      patients with AF. METHODS AND RESULTS: We randomly assigned 712 patients with AF
      to nurse-led care and usual care. Nurse-led care consisted of guidelines based,
      software supported integrated chronic care supervised by a cardiologist. The
      primary endpoint was a composite of cardiovascular hospitalization and
      cardiovascular death. Duration of follow-up was at least 12 months. Adherence to
      guideline recommendations was significantly better in the nurse-led care group.
      After a mean of 22 months, the primary endpoint occurred in 14.3% of 356 patients
      of the nurse-led care group compared with 20.8% of 356 patients receiving usual
      care [hazard ratio: 0.65; 95% confidence interval (CI) 0.45-0.93; P= 0.017].
      Cardiovascular death occurred in 1.1% in the nurse-led care vs. 3.9% in the usual
      care group (hazard ratio: 0.28; 95% CI: 0.09-0.85; P= 0.025). Cardiovascular
      hospitalization amounted (13.5 vs. 19.1%, respectively, hazard ratio: 0.66; 95%
      CI: 0.46-0.96, P= 0.029). CONCLUSION: Nurse-led care of patients with AF is
      superior to usual care provided by a cardiologist in terms of cardiovascular
      hospitalizations and cardiovascular mortality. Trial registration information:
      Clinicaltrials.gov identifier number: NCT00391872.

PMID- 22453655
TI  - Margarines supplemented with low dose n-3 fatty acids are not effective in
      secondary prevention.

PMID- 22453656
TI  - Myocardial infarction after scuba diving.

PMID- 22453657
TI  - Single heterozygote splice mutation in the ABCA1 gene is associated with diffuse
      atherosclerotic disease in a low high-density lipoprotein syndrome.

PMID- 22453659
TI  - 16S rRNA gene sequences analysis of Ficus elastica rubber latex degrading
      thermophilic Bacillus strain ASU7 isolated from Egypt.
AB  - A thermophilic Bacillus strain ASU7 was isolated from soil sample collected from
      Assiut governorate in Upper Egypt on latex rubber-containing medium at 45 
      degrees C. Genetically, the 16S bacterial ribosomal RNA gene of the strain ASU7
      was amplified by the polymerase chain reaction (PCR) and sequenced. The sequence
      of the PCR product was compared with known 16S rRNA gene sequences in the GenBank
      database. Based on phylogenetic analyses, strain ASU7 was identified as Bacillus
      amyloliquefaciens. The strain was able to utilize Ficus elastica rubber latex as
      a sole source for carbon and energy. The ability for degradation was determined
      by measuring the increase in protein content of bacterium (mg/g dry wt),
      reduction in molecular weight (g/mol), and inherent viscosity (dl/g) of the
      latex. Moreover, the degradation was also confirmed by observing the growth of
      bacterium and formation of aldehyde or keto group using scanning electron
      microscopy (SEM) and shiff's reagent, respectively.

PMID- 22453658
TI  - Long-term alcohol consumption in relation to all-cause and cardiovascular
      mortality among survivors of myocardial infarction: the Health Professionals
      Follow-up Study.
AB  - AIMS: The aim of this study was to examine the association between long-term
      alcohol consumption, alcohol consumption before and after myocardial infarction
      (MI), and all-cause and cardiovascular mortality among survivors of MI. METHODS
      AND RESULTS: The Health Professionals Follow-up Study (HPFS) is a prospective
      cohort study of 51 529 US male health professionals. From 1986 to 2006, 1818 men
      were confirmed with incident non-fatal MI. Among MI survivors, 468 deaths were
      documented during up to 20 years of follow-up. Long-term average alcohol
      consumption was calculated beginning from the time period immediately before the
      first MI and updated every 4 years afterward. Cox proportional hazards were used
      to estimate the multivariable-adjusted hazard ratios (HR) and 95% confidence
      intervals (CI). Compared with non-drinkers, the multivariable-adjusted HRs for
      all-cause mortality were 0.78 (95% CI: 0.62-0.97) for 0.1-9.9 g/day, 0.66 (95%
      CI: 0.51-0.86) for 10.0-29.9 g/day, and 0.87 (95% CI: 0.61-1.25) for >=30 g/day
      (P(quadratic)= 0.006). For cardiovascular mortality, the corresponding HRs were
      0.74 (95% CI: 0.54-1.02), 0.58 (95% CI: 0.39-0.84), and 0.98 (95% CI: 0.60-1.60),
      P(quadratic)= 0.003. These findings were consistent when restricted to pre- and
      post-MI alcohol assessments. In subgroup analyses, moderate alcohol consumption
      was inversely associated with mortality among men with non-anterior infarcts, and
      among men with mildly diminished left ventricular function. CONCLUSION: Long-term
      moderate alcohol consumption is inversely associated with all-cause and
      cardiovascular mortality among men who survived a first MI. This U-shaped
      association may be strongest among individuals with less impaired cardiac
      function after MI and should be examined further.

PMID- 22453661
TI  - Site-specific bacterial chromosome engineering: PhiC31 integrase mediated
      cassette exchange (IMCE).
AB  - The bacterial chromosome may be used to stably maintain foreign DNA in the mega
      base range. Integration into the chromosome circumvents issues such as plasmid
      replication, plasmid stability, plasmid incompatibility, and plasmid copy number
      variance. This method uses the site-specific integrase from the Streptomyces
      phage (Phi) C31. The PhiC31 integrase catalyzes a direct recombination between
      two specific DNA sites: attB and attP (34 and 39 bp, respectively). This
      recombination is stable and does not revert. A "landing pad" (LP) sequence
      consisting of a spectinomycin-resistance gene, aadA (SpR), and the E. coli beta
      glucuronidase gene (uidA) flanked by attP sites has been integrated into the
      chromosomes of Sinorhizobium meliloti, Ochrobactrum anthropi, and Agrobacterium
      tumefaciens in an intergenic region, the ampC locus, and the tetA locus,
      respectively. S. meliloti is used in this protocol. Mobilizable donor vectors
      containing attB sites flanking a stuffer red fluorescent protein (rfp) gene and
      an antibiotic resistance gene have also been constructed. In this example the
      gentamicin resistant plasmid pJH110 is used. The rfp gene may be replaced with a
      desired construct using SphI and PstI. Alternatively a synthetic construct
      flanked by attB sites may be sub-cloned into a mobilizable vector such as
      pK19mob. The expression of the PhiC31 integrase gene (cloned from pHS62) is
      driven by the lac promoter, on a mobilizable broad host range plasmid pRK7813. A
      tetraparental mating protocol is used to transfer the donor cassette into the LP
      strain thereby replacing the markers in the LP sequence with the donor cassette.
      These cells are trans-integrants. Trans-integrants are formed with a typical
      efficiency of 0.5%. Trans-integrants are typically found within the first 500
      1,000 colonies screened by antibiotic sensitivity or blue-white screening using 5
      bromo-4-chloro-3-indolyl-beta-D-glucuronic acid (X-gluc). This protocol contains
      the mating and selection procedures for creating and isolating trans-integrants.

PMID- 22453662
TI  - Design of novel BH3 mimetics for the treatment of chronic lymphocytic leukemia.
AB  - Impaired programmed cell death is an important factor in the pathogenesis of
      chronic lymphocytic leukemia (CLL) and in the development of resistance to
      chemoimmunotherapy. Hence, the reactivation of apoptotic processes is likely to
      be a pertinent strategy for circumventing this resistance. Proteins from the Bcl
      2 family are critical elements in defective apoptosis. Some compounds induce the
      apoptosis of CLL cells ex vivo by downregulation of prosurvival members of this
      family (for example, Bcl-2 and Mcl-1), whereas others act by upregulation of
      proapoptotic Bcl-2 homology (BH) 3-only members (for example, Noxa and Bim). The
      concept of BH3 mimetics was prompted by the fact that BH3-only proteins are
      specific antagonistic ligands of prosurvival Bcl-2 family members. This led to
      the design of small molecules capable of inhibiting the activity of prosurvival
      Bcl-2 proteins and inducing apoptosis in leukemia cells in vitro and antileukemic
      effects in animal models. Several putative or actual BH3 mimetics are currently
      being trialed in the clinic. Two novel BH3 mimetics that can specifically bind to
      and antagonize Mcl-1 (a crucial antiapoptotic factor in CLL) have recently been
      discovered. The evaluation of this type of compound's clinical impact in CLL can
      now be considered.

PMID- 22453664
TI  - How do dyspnoea scales compare with measurement of  functional capacity in
      patients with COPD and at risk of COPD?
AB  - BACKGROUND: In primary care, formal functional capacity testing is not always
      feasible. Guidelines for family practitioners suggest the use of dyspnoea scales
      to assess exercise tolerance in patients with chronic obstructive pulmonary
      disease (COPD). AIMS: To examine whether the use of activity-based dyspnoea
      scales can substitute for actual functional capacity testing. METHODS: 128
      subjects (49% at risk of COPD, 24% GOLD stage I, 17% GOLD stage II, 9% GOLD stage
      III) performed an Incremental Shuttle Walk Test (ISWT) and completed the Medical
      Research Council dyspnoea scale (MRC), Baseline Dyspnoea Index (BDI), Oxygen Cost
      Diagram (OCD), Clinical COPD Questionnaire (CCQ), and St George's Respiratory
      Questionnaire (SGRQ). RESULTS: Analysis of variance showed that the relationship
      between the ISWT and the MRC dyspnoea scale was statistically significant but
      moderate (p < 0.001, R2 = 0.166). Correlations between the ISWT and the other
      dyspnoea scales were also moderate (correlation coefficients 0.34-0.42).
      Combining the dyspnoea scales in one analysis resulted in a proportion of
      explained variance of the ISWT of 21.4% (R2 = 0.214). CONCLUSIONS: Dyspnoea
      scales cannot substitute for formal functional capacity testing. Authors of COPD
      guidelines should consider stating more specifically that the MRC and similar
      scales measure (self-reported) activity-related dyspnoea but cannot replace
      objectively measured functional capacity.

PMID- 22453665
TI  - Presidential Address: American Urogynecologic Society's Role in Moving Our Field
      Forward.

PMID- 22453663
TI  - Relationship of obesity with respiratory symptoms and  decreased functional
      capacity in adults without established  COPD.
AB  - BACKGROUND: Obesity contributes to respiratory symptoms and exercise limitation,
      but the relationships between obesity, airflow obstruction (AO), respiratory
      symptoms and functional limitation are complex. AIMS: To determine the
      relationship of obesity with airflow obstruction (AO) and respiratory symptoms in
      adults without a previous diagnosis of chronic obstructive pulmonary disease
      (COPD). METHODS: We analysed data for potential referents recruited to be healthy
      controls for an ongoing study of COPD. The potential referents had no prior
      diagnosis of COPD or healthcare utilisation attributed to COPD in the 12 months
      prior to recruitment. Subjects completed a structured interview and a clinical
      assessment including body mass index, spirometry, six-minute walk test (SMWT),
      and the Short Performance Physical Battery (SPPB). Multiple regression analyses
      were used to test the associations of obesity (body mass index >30 kg/m2) and
      smoking with AO (forced expiratory volume in 1s/forced vital capacity ratio
      <0.7). We also tested the association of obesity with respiratory symptoms and
      impaired functional capacity (SPPB, SMWT), adjusting for AO. RESULTS: Of 371
      subjects (aged 40-65 years), 69 (19%) had AO. In multivariate analysis, smoking
      was positively associated with AO (per 10 pack-years, OR 1.24; 95% CI 1.04 to
      1.49) while obesity was negatively associated with AO (OR 0.54; 95% CI 0.30 to
      0.98). Obesity was associated with increased odds of reporting dyspnoea on
      exertion (OR 3.6; 95% CI 2.0 to 6.4), productive cough (OR 2.5; 95% CI 1.1 to
      6.0), and with decrements in SMWT distance (67 +/- 9 m; 95% CI 50 to 84 m) and
      SPPB score (OR 1.9; 95% CI 1.1 to 3.5). None of these outcomes was associated
      with AO. CONCLUSIONS: Although AO and obesity are both common among adults
      without an established COPD diagnosis, obesity (but not AO) is linked to a higher
      risk of reporting dyspnoea on exertion, productive cough, and poorer functional
      capacity.

PMID- 22453666
TI  - Summary of research recommendations from the inaugural american urogynecologic
      society research summit.

PMID- 22453667
TI  - Impact of hormones on female sexual function and dysfunction.
AB  - The female sexual response cycle is a complex system composed of physiologic
      changes, psychological, and cultural factors. Female sexual dysfunction (FSD)
      encompasses a variety of sexual problems, including low desire or interest,
      diminished arousal, difficulties with orgasm, and dyspareunia. Research in female
      sexual function and dysfunction has lagged significantly behind males despite our
      current knowledge that FSD can occur in as many of 80% of the female population.
      Basic science research exists but also identifies serious gaps in our fundamental
      knowledge of this area. The purpose of this article was to review our current
      understanding of the effects of hormones on normal physiologic sexual responses
      in women, female sexual function and dysfunction, and the available treatment
      options for the various components of FSD.

PMID- 22453668
TI  - Urgency urinary incontinence in women 50 years or older: incidence, remission,
      and predictors of change.
AB  - OBJECTIVES: : To estimate 2-year incidence, remission, and predictors of urgency
      urinary incontinence (UUI) in a community-based population of women 50 years or
      older. METHODS: : We analyzed the 2004 to 2006 data in the Health and Retirement
      Study. Subjects were women 50 years or older with baseline and follow-up UUI
      information. Urgency urinary incontinence incidence and remission were
      calculated. Predictors of UUI progression and improvement were estimated
      controlling for age, ethnicity, body mass index, parity, psychiatric illness,
      medical comorbidities, functional limitations, and stress urinary incontinence.
      We evaluated whether baseline UUI status predicted follow-up status and used
      multivariable logistic regression to identify predictor variables. RESULTS: : A
      total of 8581 women reported UUI status at baseline and follow-up. Of 7244 women
      continent at baseline, 268 affirmed UUI at follow-up for a 2-year incidence of
      3.7%. Of 581 women with UUI at baseline, 150 were continent at follow-up for a 2
      year remission of 25.8%. Predictors of UUI development included increased age
      (7th and 10th decades compared with 6th decade; OR, 1.5 and 7.2; confidence
      interval [CI], 1.1-2.1 and 4.2-12.5, respectively), obesity (OR, 1.6; CI, 1.2
      2.1), history of psychiatric illness (OR, 1.6; CI, 1.3-2.0), functional
      limitations (OR, 6.2; CI, 4.2-9.2), and stress urinary incontinence (OR, 5.0; CI,
      3.0-8.3). Women who denied UUI at baseline were also likely to deny UUI at follow
      up (OR, 47.4; CI, 22.9-98.1). CONCLUSIONS: : In this community-based population
      of women 50 years or older, UUI incidence was low and remission was high.
      Predictors of UUI included increased age, severe obesity, functional limitations,
      a positive psychiatric history, and incontinence status at baseline.

PMID- 22453669
TI  - Efficacy of Solifenacin on Overactive Bladder Symptoms, Symptom Bother, and Other
      Patient-Reported Outcomes in Subjects With or Without Incontinence: A Post Hoc
      Analysis of Data From VIBRANT.
AB  - OBJECTIVE: : To evaluate the efficacy of solifenacin versus placebo by baseline
      continence status using post hoc analysis. METHODS: : Patients with overactive
      bladder (OAB) were randomized to solifenacin or placebo for 12 weeks; patient
      reported outcome (PRO) measures and bladder diaries were completed at
      prespecified time points. VESIcare Investigation of Bother and Quality of Life in
      Subjects with OAB (VIBRANT) was not designed to show treatment differences within
      continence status subgroups. RESULTS: : In the full analysis set (n = 750), 73%
      of patients were incontinent (n = 545) at baseline. After 12 weeks, incontinent
      patients receiving solifenacin showed significant improvements versus placebo on
      PRO measures and most diary-based end points; continent patients (n = 205) showed
      smaller but similar treatment-related changes. Tolerability was similar in both
      subgroups and by treatment; most frequent adverse events were dry mouth and
      constipation. CONCLUSIONS: : In the VIBRANT study, solifenacin significantly
      improved OAB symptom bother, health-related quality of life, and most symptoms
      versus placebo in incontinent patients. Continent patients showed smaller but
      similar trends. Solifenacin was well tolerated in both subgroups.

PMID- 22453670
TI  - Dietary consumption triggers in interstitial cystitis/bladder pain syndrome
      patients.
AB  - OBJECTIVES: : The aim of this study was to survey interstitial cystitis/bladder
      pain syndrome (IC/BPS) patients with a Web-based questionnaire to determine which
      consumables (foods, drinks, supplements/spices, and general food categories)
      truly exacerbate IC/BPS symptoms. METHODS: : The Interstitial Cystitis
      Association posted a Web link on its Web site offering its members participation
      in the Web-based questionnaire from April 2009 to February 2010. Members were
      asked questions on the effect of 344 different foods, drinks, supplements,
      condiments/spices, and general food categories on urinary frequency, urgency,
      and/or pelvic pain symptoms. Members were asked to score symptoms related to
      consumables on a symptom Likert scale of 0 to 5. Questions on ethnicity,
      education, symptom duration, seasonal allergies, irritable bowel syndrome, and
      specific diets were included. RESULTS: : There were 598 complete responses to the
      questionnaire, and 95.8% of the participants answered that certain foods and
      beverages affected their IC/BPS symptoms. Most items had no effect on symptoms.
      Items that made symptoms worse were citrus fruits, tomatoes, coffee, tea,
      carbonated and alcoholic beverages, spicy foods, artificial sweeteners, and
      vitamin C. Only calcium glycerophosphate (Prelief; AK Pharma, Inc, Pleasantville,
      NJ) and sodium bicarbonate (baking soda) had a trend toward improvement in
      symptoms. CONCLUSIONS: : Interstitial cystitis diets do not have to be overly
      restrictive. It is recommended that patients with IC/BPS avoid citrus fruits,
      tomatoes, coffee, tea, carbonated and alcoholic beverages, spicy foods,
      artificial sweeteners, and vitamin C. The use of calcium glycerophosphate and/or
      sodium bicarbonate before consumption of these trigger consumables may also help
      reduce sensitivity.

PMID- 22453671
TI  - Use of composite grafts in abdominal sacrocolpopexy.
AB  - OBJECTIVE: : The ideal graft material for pelvic reconstructive surgery remains
      undetermined. The purpose of this study was to present data on novel composite
      biologic/synthetic grafts during use in abdominal sacrocolpopexy. METHODS: : A
      case series of 90 patients undergoing abdominal sacrocolpopexy with composite
      biologic/synthetic grafts was conducted. The primary outcome was graft erosion.
      Assuming a 3% risk of reoperation for mesh erosion, the number needed to treat
      with a composite graft in order to avoid erosion risk from a synthetic-only graft
      was calculated. The cost of a composite graft was compared to reoperation costs
      for mesh erosion of a synthetic-only graft. RESULTS: : Zero patients (N = 90)
      undergoing abdominal sacrocolpopexy with a composite biologic/synthetic graft
      experienced graft erosion. Based on existing data, thirty-three patients would
      need to be treated with a composite graft to avoid one mesh erosion from a
      synthetic-only graft. If a $500 composite graft is used, the cost of reoperation
      performed abdominally is higher. CONCLUSIONS: : This study introduces a novel
      biologic/synthetic composite graft that offers the advantage of low erosion risk
      during use in abdominal sacrocolpopexy. Combined grafts may also be cost
      effective. Future research should focus on exploring the role of these durable,
      yet low erosion risk grafts to potentially promote improved safety for our
      patients and cost savings for society.

PMID- 22453672
TI  - Robotic-assisted and laparoscopic sacrocolpopexy: comparing operative times,
      costs and outcomes.
AB  - OBJECTIVES: : To compare operative times, hospital costs, and surgical outcomes
      for robotic-assisted laparoscopic sacrocolpopexy (RALSC) and laparoscopic
      sacrocolpopexy (LSC). METHODS: : A retrospective cohort study of 104 subjects who
      underwent RALSC (n = 43) or LSC (n = 61) for vaginal vault prolapse was
      performed. The primary outcomes were operative time and hospital costs. The
      secondary outcomes included blood loss, complications, and objective cure rates.
      chi and t tests were used. RESULTS: : The mean operative time was longer in RALSC
      than in LSC (281 +/- 58 vs 206 +/- 42 minutes; P < 0.001) with setup time
      accounting for only 9 minutes of this difference. Direct costs (expressed in cost
      units) for hospital stay were similar (437 +/- 88 vs 450 +/- 119 units; P =
      0.738) while surgical costs remained higher for RALSC (2724 +/- 413 vs 2295 +/-
      342 units; P < 0.01). Blood loss and complications were similar, and objective
      cure was not significantly different for RALSC vs LSC (90% vs 80%, P = 0.19).
      CONCLUSIONS: : Robotic-assisted laparoscopic sacrocolpopexy achieves similar
      perioperative outcomes compared to LSC with increased surgical time resulting in
      increased costs.

PMID- 22453673
TI  - Transobturator tape removal using a combined vaginal-transcutaneous approach for
      intractable groin pain.
AB  - BACKGROUND: : Transient groin pain is a therapeutically challenging complication
      associated with transobturator sling procedures. CASE: : We present the case of a
      37-year-old woman who presented with debilitating left groin pain and dyspareunia
      following placement of transobturator sling. Pelvic floor physical therapy,
      medications, and trigger point injections failed to provide relief. Workup
      included magnetic resonance imaging of the pelvis, complex cystometrics, and
      additional trigger point injections. Surgical removal of the complete left side
      of the tape including the portion imbedded in the obturator foramen was performed
      with a combined vaginal-transcutaneous approach. Extirpation of the mesh arm
      brought prompt and full resolution of the patient's symptoms. CONCLUSIONS: :
      Surgical removal of the transobturator tape through the obturator foramen can be
      safely performed using a combined vaginal-transcutaneous approach.

PMID- 22453674
TI  - Type 1 diabetes mellitus in India.

PMID- 22453675
TI  - Randomized controlled multicenter international clinical trial of self-gripping
      ParietexTM ProGripTM polyester mesh versus lightweight polypropylene mesh in open
      inguinal hernia repair: interim results at 3 months.
AB  - PURPOSE: To compare clinical outcomes following sutureless ParietexTM ProGripTM
      mesh repair to traditional Lichtenstein repair with lightweight polypropylene
      mesh secured with sutures. METHODS: This is a 3-month interim report of a 1-year
      multicenter international study. Three hundred and two patients were randomized;
      153 were treated with Lichtenstein repair (L group) and 149 with ParietexTM
      ProGripTM precut mesh (P group) with or without fixation. The primary outcome
      measure was postoperative pain using the visual analog scale (VAS, 0-150 mm);
      other outcomes were assessed prior to surgery and up to 3 months postoperatively.
      RESULTS: Compared to baseline, pain score was lower in the P group at discharge (
      10%) and at 7 days (-13%), while pain increased in the L group at discharge
      (+39%) and at 7 days (+21%). The difference between groups was significant at
      both time points (P = 0.007 and P = 0.039, respectively). In the P group,
      patients without fixation suffered less pain compared to those with single-suture
      fixation (1 month: -20.9 vs. -6.15%, P = 0.02; 3 months: -24.3 vs. -7.7%, P =
      0.01). The infection rate was significantly lower in the P group during the 3
      month follow-up (2.0 vs. 7.2%, P = 0.032). Surgery duration was significantly
      shorter in the P group (32.4 vs. 39.1 min; P < 0.001). No recurrence was observed
      at 3 months in both groups. CONCLUSIONS: Surgery duration, early postoperative,
      pain and infection rates were significantly reduced with self-gripping polyester
      mesh compared to Lichtenstein repair with polypropylene mesh. The use of fixation
      increased postoperative pain in the P group. The absence of early recurrence
      highlights the gripping efficiency effect.

PMID- 22453677
TI  - Synthesis, structure, properties and immobilization on a gold surface of the
      monoribbed-functionalized tris-dioximate cobalt(II) clathrochelates and an
      electrocatalytic hydrogen production from H+ ions.
AB  - The cycloaddition of the mono- and dichloroglyoximes to the cobalt(II) bis-alpha
      benzyldioximate afforded the cobalt(II) mono- and dichloroclathrochelates in
      moderate yields (40-60%). These complexes undergo nucleophilic substitution of
      their reactive chlorine atoms with aliphatic amines, alcohols and thiolate
      anions. In the case of ethylenediamine and 1,2-ethanedithiol, only the
      macrobicyclic products with alpha,alpha'-N(2)- and alpha,alpha'-S(2)-alicyclic
      six-numbered ribbed fragments were obtained. The cobalt(II) cage complexes with
      terminal mercapto groups were synthesized using aliphatic dithiols. The crystal
      and molecular structures of the six cobalt(II) clathrochelates were obtained by X
      ray diffraction. Their CoN(6)-coordination polyhedra possess a geometry
      intermediate between a trigonal prism and a trigonal antiprism, and the
      encapsulated cobalt(II) ions are shifted from their centres due to the structural
      Jahn-Teller effect with the Co-N distances varying significantly (by 0.10-0.26
      A). The electrochemistry of the complexes obtained was studied by cyclic
      voltammetry (CV). The anodic waves correspond to the quasi-reversible Co(2+/3+)
      oxidations, whereas the cathodic ranges contain the quasi-reversibile waves
      assigned to the Co(2+/+) reductions; all the cobalt(i)-containing clathrochelate
      anions formed are stable in the CV time scale. The electrocatalytic properties of
      the cobalt complexes obtained were studied in the production of hydrogen from
      H(+) ions: the addition of HClO(4) resulted in the formation of the same
      catalytic cathodic reduction Co(2+/+) waves. The controlled-potential
      electrolysis with gas chromatography analysis confirmed the production of H(2) in
      high Faraday yields. The efficiency of this electrocatalytic process was enhanced
      by an immobilization of the complexes with terminal mercapto groups on a surface
      of the working gold electrode.

PMID- 22453676
TI  - Thyroid function and perfluoroalkyl acids in children living near a chemical
      plant.
AB  - BACKGROUND: Animal studies suggest that some perfluoroalkyl acids (PFAAs),
      including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and
      perfluorononanoic acid (PFNA) may impair thyroid function. Epidemiological
      findings, mostly related to adults, are inconsistent. OBJECTIVES: We investigated
      whether concentrations of PFAAs were associated with thyroid function among
      10,725 children (1-17 years of age) living near a Teflon manufacturing facility
      in the Mid-Ohio Valley (USA). METHODS: Serum levels of thyroid-stimulating
      hormone (TSH), total thyroxine (TT4), and PFAAs were measured during 2005-2006,
      and information on diagnosed thyroid disease was collected by questionnaire.
      Modeled in utero PFOA concentrations were based on historical information on PFOA
      releases, environmental distribution, pharmacokinetic modeling, and residential
      histories. We performed multivariate regression analyses. RESULTS: Median
      concentrations of modeled in utero PFOA and measured serum PFOA, PFOS, and PFNA
      were 12, 29, 20, and 1.5 ng/mL, respectively. The odds ratio for hypothyroidism
      (n = 39) was 1.54 [95% confidence interval (CI): 1.00, 2.37] for an interquartile
      range (IQR) contrast of 13 to 68 ng/mL in serum PFOA measured in 2005-2006.
      However, an IQR shift in serum PFOA was not associated with TSH or TT4 levels in
      all children combined. IQR shifts in serum PFOS (15 to 28 ng/mL) and serum PFNA
      (1.2 to 2.0 ng/mL) were both associated with a 1.1% increase in TT4 in children 1
      17 years old (95% CIs: 0.6, 1.5 and 0.7, 1.5 respectively). CONCLUSIONS: This is
      the first large-scale report in children suggesting associations of serum PFOS
      and PFNA with thyroid hormone levels and of serum PFOA and hypothyroidism.

PMID- 22453678
TI  - Mechanisms of delayed anti-tuberculosis protection in the lung of parenteral BCG
      vaccinated hosts: a critical role of airway luminal T cells.
AB  - The immune mechanisms underlying unsatisfactory pulmonary mucosal protection by
      parenteral Bacillus Calmette-Guerin (BCG) immunization remain poorly understood.
      We found that parenteral BCG immunization failed to elicit airway luminal T cells
      (ALT) whereas it induced significant T cells in the lung interstitium. After
      Mycobacterium tuberculosis (M.tb) challenge, ALT remained missing for 10 days.
      The lack of ALT correlated with lack of lung protection for 14 days post-M.tb
      challenge. To further investigate the role of ALT, ALT were elicited in BCG
      immunized animals by intranasal inoculation of M.tb culture-filtrate (CF)
      proteins. Installment of ALT by CF restored protection in the early phases of
      M.tb infection, which was linked to rapid increases in ALT, but not in lung
      interstitial T cells. Also, adoptive transfer of T cells to the airway lumen of
      BCG-immunized animals also accelerated protection. This study thus provides novel
      evidence that unsatisfactory lung protection by parenteral BCG immunization is
      due to delayed ALT recruitment after pulmonary M.tb exposure.

PMID- 22453680
TI  - A novel one-pot de-blocking and conjugation reaction step leads to process
      intensification in the manufacture of PEGylated insulin IN-105.
AB  - Bio-catalytic in vitro multistep reactions can be combined in a single step in
      one pot by optimizing multistep reactions under identical reaction condition.
      Using this analogy, the process of making PEGylated insulin, IN-105, was
      simplified. Instead of taking the purified active insulin bulk powder as the
      starting material for the conjugation step, an insulin process intermediate,
      partially purified insulin ester, was taken as starting material. Process
      intensification (PI) was established by performing a novel de-blocking (de
      esterification) of the partially purified insulin ester and conjugation at B-29
      Lys residue of B chain with a short-chain methoxy polyethylene glycol (mPEG) in a
      single-pot reactor. The chromatographic profile at the end of the reaction was
      found similar irrespective of whether both the reactions were performed
      sequentially or simultaneously. The conjugated product of interest, IN-105
      (conjugation at LysB(29)), was purified from the heterogeneous mixture of
      conjugated products. The new manufacturing process was deduced to be more
      simplified and economical in making the insulin conjugates as several downstream
      purification steps could be circumvented. The physicochemical characteristics of
      IN-105 manufactured through this economic process was found to be indifferent
      from the product formed through the traditional process where the conjugation
      starting material was purified from bulk insulin.

PMID- 22453679
TI  - MiR-375 is downregulated in epithelial cells after IL-13 stimulation and
      regulates an IL-13-induced epithelial transcriptome.
AB  - Interleukin 13 (IL-13)-induced epithelial gene and protein expression changes are
      central to the pathogenesis of multiple allergic diseases. Herein, using human
      esophageal squamous and bronchial columnar epithelial cells, we identified
      microRNAs (miRNAs) that were differentially regulated after IL-13 stimulation.
      Among the IL-13-regulated miRNAs, miR-375 showed a conserved pattern of
      downregulation. Furthermore, miR-375 was downregulated in the lung of IL-13 lung
      transgenic mice. We subsequently analyzed miR-375 levels in a human disease
      characterized by IL-13 overproduction--the allergic disorder eosinophilic
      esophagitis (EE)--and observed downregulation of miR-375 in EE patient samples
      compared with control patients. MiR-375 expression levels reflected disease
      activity, normalized with remission, and inversely correlated with the degree of
      allergic inflammation. Using a lentiviral strategy and whole-transcriptome
      analysis in epithelial cells, miR-375 overexpression was sufficient to markedly
      modify IL-13-associated immunoinflammatory pathways in epithelial cells in vitro,
      further substantiating interactions between miR-375 and IL-13. Taken together,
      our results support a key role of miRNAs, particularly miR-375, in regulating and
      fine-tuning IL-13-mediated responses.

PMID- 22453681
TI  - Substrate mass transport in two-phase partitioning bioreactors employing liquid
      and solid non-aqueous phases.
AB  - The mass transfer of phenol and butyl acetate to/from water was studied in two
      phase partitioning bioreactors using immiscible organic solvents and solid
      polymer beads as the partitioning phases in a 5-L stirred tank bioreactor.
      Virtually instantaneous mass transfer was observed with phenol in water/2
      undecanone, and with butyl acetate in water/silicone oil systems. The mass
      transfer of butyl acetate to silicone oil was rapid irrespective of the viscosity
      of the partitioning phase. When Hytrel(r) polymer beads were employed as the
      partitioning phase, substrate transport to the polymer was found not to be
      externally mass transfer limited, but rather internally by substrate diffusion
      into the polymer. In contrast to gaseous, poorly soluble substrates studied in
      other works, mass transfer of soluble substrates such as phenol and butyl acetate
      to the polymer was unaffected by impeller speed but rather by polymer mass
      fraction.

PMID- 22453683
TI  - Laser-induced thrombus formation in mouse brain microvasculature: effect of
      clopidogrel.
AB  - Antiplatelet drugs have been evaluated by measuring platelet aggregation ex vivo,
      but in vivo studies were scanty. The purpose of this study was to observe the
      effects of an antiplatelet agent (clopidogrel) on the process of laser-induced
      thrombus formation in mice using intravital fluorescence microscopy. C57 BL/6J
      mice (n = 19) were anesthetized using chloral hydrate. The head of each mouse was
      fixed with a head holder, and a cranial window was made in the parietal region.
      Platelets were labeled in vivo by intravenous administration of
      carboxyfluorescein diacetate succinimidyl ester. Clopidogrel (1 mg/kg, n = 6; 10
      mg/kg, n = 6) was administered orally for 2 days before the experiment. Another
      seven mice were used as controls. Laser irradiation (1,000 mA, 9.8 mW, diode
      pumped solid-state (DPSS) laser 532 nm) was directed for 4 s at pial arteries to
      induce thrombus formation. Labeled platelets and thrombus were observed
      continuously under fluorescence microscopy. We recorded the area of thrombus
      after 30 min and determined the complete occlusion rate. After laser irradiation
      to the pial artery, complete occlusion rate was significantly lower in the
      clopidogrel (10 mg/kg) group (16%, 4/25 vessels) than in the control group (60%,
      12/20 vessels) or clopidogrel (1 mg/kg) group (55%, 11/20 vessels). Area of
      platelet thrombus at 30 min after laser irradiation was significantly smaller in
      the clopidogrel (10 mg/kg) group (209 +/- 128 MUm(2)) than in the control group
      (358 +/- 256 MUm(2)) or clopidogrel (1 mg/kg) group (355 +/- 57 MUm(2)). The
      apparatus which we developed is convenient for inducing thrombus formation by
      causing endothelial cell damage to the brain surface vasculature in small animals
      without damage of extravascular tissue. Clopidogrel significantly inhibited laser
      induced thrombus formation in pial arteries of mice in a dose-dependent manner.

PMID- 22453682
TI  - Genetically modified pigs for biomedical research.
AB  - During the last two decades, pigs have been used to develop some of the most
      important large animal models for biomedical research. Advances in pig genome
      research, genetic modification (GM) of primary pig cells and pig cloning by
      nuclear transfer, have facilitated the generation of GM pigs for
      xenotransplantation and various human diseases. This review summarizes the key
      technologies used for generating GM pigs, including pronuclear microinjection,
      sperm-mediated gene transfer, somatic cell nuclear transfer by traditional
      cloning, and somatic cell nuclear transfer by handmade cloning. Broadly used
      genetic engineering tools for porcine cells are also discussed. We also summarize
      the GM pig models that have been generated for xenotransplantation and human
      disease processes, including neurodegenerative diseases, cardiovascular diseases,
      eye diseases, bone diseases, cancers and epidermal skin diseases, diabetes
      mellitus, cystic fibrosis, and inherited metabolic diseases. Thus, this review
      provides an overview of the progress in GM pig research over the last two decades
      and perspectives for future development.

PMID- 22453684
TI  - Limitations of conventional anticoagulant therapy and the promises of non-heparin
      based conformational activators of antithrombin.
AB  - An elevated prothrombotic state is a major risk factor for venous
      thromboembolism, atrial fibrillation and cardiac strokes. The regulation of
      various coagulation cascade proteases plays an important role in determining a
      prothrombotic state. Clinically used anticoagulants are inhibitor of enzymes that
      are involved in the coagulation pathway, primarily thrombin and factor Xa. The
      conformational activation of antithrombin by heparin is a critical step in the
      inhibition of factor Xa by antithrombin. Despite heparin being the most potent
      physiological activator which enhances the otherwise very lethargic antithrombin
      inhibition of factor Xa by approximately 1,000-fold, the conventional heparin
      therapy poses serious complications because of heparin's polyanionic nature and
      its cross-reactivity. A number of attempts have been carried out in designing
      alternative non-heparin based conformational activators of antithrombin for
      factor Xa inhibition. Studies have demonstrated appreciable activation of
      antithrombin by small organic molecules, but not much is known about the
      specificity and effects of these molecules on structure and stability. It is
      assumed that these activators of antithrombin perform their function by binding
      to heparin binding site. A recently identified cavity which links the heparin
      binding site to the strand 2A for antithrombin activation also seems to be an
      ideal target apart the heparin binding site of antithrombin. There are
      opportunities in discovering more activators from naturally available organic
      scaffolds and also for modifying such scaffolds for designing better
      conformational activators with minimum associated complications. This review
      summarizes the current literature on the mainstay anticoagulants and non-heparin
      based antithrombin conformation modulators.

PMID- 22453686
TI  - Assessing teratogenic changes in a zebrafish model of fetal alcohol exposure.
AB  - Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to
      ethanol. It presents with characteristic defects to the face and organs,
      including mental retardation due to disordered and damaged brain development.
      Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of
      birth defects that occur due to maternal alcohol consumption, and occurs in
      approximately 4% of children born in the United States. With 50% of child-bearing
      age women reporting consumption of alcohol, and half of all pregnancies being
      unplanned, unintentional exposure is a continuing issue. In order to best
      understand the damage produced by ethanol, plus produce a model with which to
      test potential interventions, we developed a model of developmental ethanol
      exposure using the zebrafish embryo. Zebrafish are ideal for this kind of
      teratogen study. Each pair lays hundreds of eggs, which can then be collected
      without harming the adult fish. The zebrafish embryo is transparent and can be
      readily imaged with any number of stains. Analysis of these embryos after
      exposure to ethanol at different doses and times of duration and application
      shows that the gross developmental defects produced by ethanol are consistent
      with the human birth defect. Described here are the basic techniques used to
      study and manipulate the zebrafish FAS model.

PMID- 22453688
TI  - Editorial board changes.

PMID- 22453687
TI  - Kinetics and mechanism of organocatalytic aza-Michael additions: direct
      observation of enamine intermediates.
AB  - The imidazoles 1a-g add to the CC-double bond of the iminium ion 2 with rate
      constants as predicted by the equation log k = s(N)(N + E). Unfavourable proton
      shifts from the imidazolium unit to the enamine fragment in the adduct 3 account
      for the failure of imidazoles to take part in iminium-activated aza-Michael
      additions to enals.

PMID- 22453689
TI  - Redefinition of the pelvic connective tissue: in situ histologic examination.
AB  - OBJECTIVES: : The objectives of this study were to find a common perspective in
      clinical and gross/systemic anatomy for the pelvic connective tissue
      (subperitoneal fascia) and to establish a new pelvic anatomy. METHODS: : The
      histologic sections from 5 fixed cadavers were obtained from a total of 17 fixed
      and 11 fresh cadavers. On the basis of our past surgical and research findings,
      the relationship between the pelvic organs and the pelvic connective tissue was
      observed from in situ histologic sections of the whole pelvis. RESULTS: :
      Subperitoneal fasciae, a term that is expressed in gross/systemic anatomy, were
      manifested as a 3-dimensional structure by a complex of "ligaments," as defined
      in clinical terminology. In the supine position, this structure consisted of the
      sagittal plane formed by the rectouterine ligament and vesicouterine ligament;
      the perpendicular plane by the vesicohypogastric fascia, transverse cervical
      ligament, and lateral rectal ligament; and the horizontal plane by the superior
      fascia of the levator ani muscle. CONCLUSIONS: : The ligaments were regarded as a
      compatible component of the subperitoneal fascia. Our anatomical concept of the
      pelvic connective tissue differed from that for classic clinical anatomy.

PMID- 22453690
TI  - Current Use of Pelvic Organ Prolapse Quantification by AUGS and ICS Members.
AB  - OBJECTIVE: : To determine the current use of the pelvic organ prolapse
      quantification (POP-Q) by members of the American Urogynecologic Society (AUGS)
      and the International Continence Society (ICS). METHODS: : Surgically active
      members of AUGS and ICS completed a Web-based questionnaire about their use of
      the POP-Q and included queries regarding respondent's clinical training, surgical
      experience, and practice setting. Users of POP-Q described their POP-Q use
      including patient's position, tools used to measure or assist with exposure, use
      of strain, and bladder volume. Strengths and weaknesses of the POP-Q system were
      also assessed. RESULTS: : The 308 respondents had a median of 8 years (range, 0
      35 years) of independent performance of POP surgery. Most were from the United
      States (70%), in a shared practice (64%), with at least 2 years of fellowship
      training (61%), and had trainees participating in patient care (81%). Of the
      respondents, 76% reported using the POP-Q; however, the technique of POP-Q
      varied. Of the 24% not using the POP-Q, two-thirds reported past POP-Q use. For
      these individuals, prolapse description was done using Baden-Walker (57%),
      descriptive words (38%), or other grades (7%). More than 50% of nonusers reported
      that the POP-Q is "too time-consuming" or that their "colleagues do not use it."
      CONCLUSIONS: : Although most surveyed members of AUGS and ICS are using the POP
      Q, we detected variability in the day-to-day practice of POP-Q use. To further
      advance the communication benefits of the POP-Q, a revision that provides
      evidence-based guidance may be a worthwhile refinement.

PMID- 22453691
TI  - Effect of flatal incontinence on sexual function.
AB  - OBJECTIVE: : To determine whether flatal incontinence (FI) adversely affects
      sexual function. METHODS: : A database of 1203 women presenting to a consultative
      urogynecology practice was queried. The Pelvic Floor Distress Inventory Short
      Form (PFDI-20) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function
      (PISQ-12) questionnaires were administered on presentation to the practice.
      Flatal incontinence was identified by an answer of at least "somewhat" to
      question 11 of PFDI-20. Questions 9 and 10 were used to eliminate confounding
      effects of leakage of solid and liquid stool. Univariate analyses were performed
      using Student t and chi tests. RESULTS: : Of the 1076 women who answered PFDI-20
      question 11, 485 subjects (46.2%) were FI and 591 (54.9%) were not flatally
      incontinent (NFI). The PFDI-20 global and all 3 subscores were higher in the FI
      than in the NFI group. Sexual activity was reported in 47.8% of subjects with FI
      and in 60.2% of the NFI group (P < 0.001). Among those who were sexually active,
      PISQ-12 scores were significantly higher in the FI group (n = 219, 15.8 +/- 6.4
      vs n = 334, 14.4 +/- 5.9, P = 0.006). After sexually active subjects with
      incontinence to stool were excluded, PFDI-20 and PISQ-12 scores were compared.
      Those with FI had significantly higher PFDI-20 global and subscores, but there
      was no significant difference in PISQ-12 scores (FI: 14.8 +/- 6.2 vs NFI: 14.0 +/
      5.7, P = 0.161). CONCLUSIONS: : Flatal incontinence is associated with decreased
      sexual activity and impaired sexual function. Flatal incontinence not accompanied
      by incontinence to stool, however, may not worsen sexual function.

PMID- 22453692
TI  - Posterior tibial nerve stimulation in patients who have failed anticholinergic
      therapy: efficacy and time to response.
AB  - OBJECTIVES: : We sought to determine the efficacy of posterior tibial nerve
      stimulation in patients who had failed anticholinergic medications. A secondary
      outcome was to determine the time to response for different parameters of
      overactive bladder. STUDY DESIGN: : The medical records of all patients treated
      with posterior tibial nerve stimulation from 2000 to 2009 seen in a university
      urogynecology practice were abstracted. Patients underwent weekly treatments.
      Patients were asked about the 4 index symptoms at each weekly visit. Descriptive
      statistics were performed on the data set using SPSS 15. RESULTS: : A total of
      141 patients were analyzed. Of these patients, 67.4% were satisfied with
      treatment results. The median week to improvement was 5 weeks for nocturia, 7
      weeks for frequency, 6 weeks for urgency, and 6 weeks for urge incontinence.
      CONCLUSIONS: : Posterior tibial nerve stimulation is an effective treatment of
      overactive bladder in patients who have failed anticholinergic therapy. Most
      patients noted improvement by 6 weeks.

PMID- 22453693
TI  - Overactive bladder and hyperlipidemia: is there an association?
AB  - OBJECTIVES: : To determine the relationship between overactive bladder (OAB),
      with or without urinary incontinence (UI), and hyperlipidemia. METHODS: : A
      random sample of 8077 primary care patients were recruited for the General
      Longitudinal Overactive Bladder Evaluation. This was a prospective population
      based survey to determine severity and occurrence of urgency, frequency,
      nocturia, and UI. A composite score of 5+ (range, 0-12) was considered to be a
      case status for OAB, and 2+ (range, 0-6) for UI. Data on hyperlipidemia were
      pulled out from the electronic medical records of all corresponding patients.
      Baseline covariates included age, education, body mass index, marital status, and
      other comorbidities. Logistic regression models were fit predicting OAB status
      (with or without UI) with prevalent hyperlipidemia as the main predictor.
      RESULTS: : A total of 3599 (45%) women older than 40 years completed the survey,
      with a mean (SD) age of 59 (13) years, median parity of 2 (range, 1-3), 66% being
      overweight or obese, 90% with at least high school education, and 66% married.
      The prevalence of OAB and UI was 33% and 35%, respectively. Prevalence of
      hyperlipidemia was 22%. The unadjusted odds ratio (OR) of OAB for those with
      versus without hyperlipidemia was significant: OR = 1.20 (95% confidence
      interval, 1.02-1.42; P = 0.029). After adjustment, this association was no longer
      significant: OR = 0.97 (95% confidence interval, 0.81-1.16; P = 0.726). Among
      women with OAB and UI, there was no association with hyperlipidemia before and
      after adjustment (P = 0.5). CONCLUSIONS: : Although on the surface there seems to
      be an association between OAB and hyperlipidemia, this association is primarily
      accounted for by other confounders.

PMID- 22453694
TI  - Risk factors for prolapse development in white, black, and Hispanic women.
AB  - OBJECTIVES: : This study aimed to examine the risk factors for prevalence and
      incidence of pelvic organ prolapse (POP) in whites, Hispanics, and blacks.
      METHODS: : This is a secondary analysis of the Women's Health Initiative (WHI)
      Estrogen plus Progestin Clinical Trial (E + P). Of the original E + P trial
      population of 16,608, 12,667 women (78.3%; 11,194 whites, 804 blacks, and 669
      Hispanics) were included in the final study sample and evaluated during the 5
      year period. The outcomes evaluated were any prolapse (WHI prolapse grades 1-3)
      and WHI prolapse grade 2 or 3. Descriptive analyses, logistic regression, and
      proportional hazard modeling were performed. RESULTS: : Increasing parity
      correlates with increasing WHI prolapse grades (0-3) in whites and blacks but not
      Hispanics. The incidence of grade 2 or 3 POP increased by 250% in white women
      with 1 child (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.68-3.71)
      in comparison to nulliparous women and grew with higher parity. For blacks, a
      weak association between the parity and grade 2 or 3 POP was noted only in women
      who had 5 or more kids (HR, 10.41; 95% CI, 1.38-78.77). Blacks were less likely
      (HR, 0.53; 95% CI, 0.40-0.71) to develop grade 2 or 3 POP compared with whites.
      For grade 2 or 3 POP, age was found to be a risk factor in whites (odds ratio
      [OR], 1.03; 95% CI, 1.02-1.04) only and body mass index (>=25 kg/m, <30 kg/m) in
      whites (OR, 1.64; 95% CI, 1.34-2.02) and Hispanics (OR, 2.87; 95% CI, 1.03-2.02).
      CONCLUSIONS: : White women are at a much greater risk for developing grade 2 or 3
      POP compared with blacks. Parity correlates most strongly with the risk of
      prolapse development in whites and possibly in grand multiparous blacks.

PMID- 22453695
TI  - Lower urinary tract symptoms in patients with uterine fibroids: association with
      fibroid location and uterine volume.
AB  - OBJECTIVE: : To examine the prevalence of lower urinary tract symptoms (LUTS) in
      women with symptomatic uterine fibroids and investigate their relationship with
      fibroid location and uterine volume. METHODS: : This was a cross-sectional study
      including 78 women seeking surgical treatment for symptomatic uterine fibroids.
      The validated Bristol Female Lower Urinary Tract Symptom-Scored Form (BFLUTS-SF)
      questionnaire was administered before surgical intervention. Uterine volume and
      BFLUTS-SF subscale scores or symptoms were compared using Student t test.
      Multivariate models explored the association between dominant fibroid location
      and BFLUTS-SF subscale scores. RESULTS: : The most prevalent LUTS were nocturia
      (91%), urgency (59%), and urinary incontinence (45%-54%). Mean uterine volume and
      length were 672 +/- 714 cm and 13 +/- 4.24 cm, respectively. Women with moderate
      and severe urinary urgency had significantly larger uterine volumes (P = 0.017).
      Mean voiding subscale scores were significantly higher in women with dominant
      anterior fibroids compared with those with non-anterior fibroids (voiding
      subscale scores, 2.84 +/- 3.03 vs 1.30 +/- 2.07, respectively; P < 0.01). This
      remained significant after adjusting for age, parity, body mass index, and
      imaging modality. CONCLUSIONS: : Lower urinary tract symptoms are prevalent in
      patients with symptomatic uterine fibroids. Further study is needed to determine
      if surgical therapy improves these LUTSs in this population.

PMID- 22453696
TI  - Use of combined anticholinergic medication and sacral neuromodulation in the
      treatment of refractory overactive bladder.
AB  - OBJECTIVES: : The objectives of this study were to determine the number of
      patients implanted with sacral neuromodulation (SNM) for overactive bladder (OAB)
      who required supplemental or continued anticholinergic (ACH) therapy for improved
      response and to identify factors predictive of requiring supplemental ACH.
      MATERIALS AND METHODS: : This is a retrospective chart review of 148 patients who
      underwent SNM from 1999 to 2007. Patients included were those implanted for
      urgency, frequency, or urge incontinence. Eighty-eight patients were included in
      the analysis. A stepwise regression analysis was performed to identify factors
      predictive for restarting ACH medication. RESULTS: : All patients underwent SNM
      implantation for frequency-urgency and urge incontinence. Of all patients, 16
      (18%) required supplemental ACH therapy for improved symptom control. Overall, 26
      patients (25%) either continued or were started on ACH therapy in addition to SNM
      for improved outcomes. CONCLUSIONS: : A subset of patients had improved
      therapeutic response with combined SNM and ACH therapy. The only factor
      associated with supplemental ACH use was body mass index.

PMID- 22453697
TI  - Multicenter Urogynecology Study on Education: Medical Student Educational
      Experiences and Knowledge Outcomes During the OBGYN Clerkship.
AB  - OBJECTIVE: : The objective of this study was to describe self-assessed student
      knowledge of female pelvic medicine (FPM) during the OBGYN clerkship. METHODS: :
      Students at 6 sites scored their knowledge of 12 FPM topics and 4 procedures both
      before and after their clerkship. Analysis included Wilcoxon tests, Spearman
      correlation, and univariate and multivariate models. RESULTS: : A total of 323
      students completed paired surveys. Mean knowledge scores (KSs) across FPM topics
      (1.40 +/- 0.12; 95% confidence interval) and procedures (0.77 +/- 0.08) increased
      significantly, with larger increases for topics (P < 0.001). Topic and procedure
      KSs were correlated (rs = 0.32, P < 0.0001). Mean KSs were significantly related
      to number and number of types of learning experiences (r = 0.13 and 0.08, both P
      < 0.001). Learning through text and inpatient encounters had independent effects
      on KS change in multivariate analysis (P = 0.01 and 0.007). CONCLUSIONS: :
      Students reported increased knowledge although less for procedures than for
      topics. Text and inpatient learning independently increased students' self
      assessed change in knowledge.

PMID- 22453698
TI  - Regarding "pelvic organ prolapse: defining the disease".

PMID- 22453699
TI  - In Response to Dr Pizarro's Letter.

PMID- 22453701
TI  - Advanced endoscopic imaging for Barrett's Esophagus: current options and future
      directions.
AB  - Barrett's esophagus is the precursor to esophageal adenocarcinoma, one of the
      most rapidly increasing cancers in the United States. Given the poor prognosis of
      late-stage adenocarcinoma, endoscopic surveillance is recommended for subjects
      with Barrett's esophagus to detect early neoplasia. Current guidelines recommend
      "random" four-quadrant biopsies taken every 1-2 cm throughout the Barrett's
      segment. However, this only samples a minority of epithelium and has been shown
      to miss areas of endoscopically- inapparent neoplasia (high grade dysplasia or
      cancer). Recent efforts have focused on developing novel diagnostic imaging
      technologies to detect the subtle epithelial changes associated with dysplasia
      and neoplasia in Barrett's esophagus. Some of these modalities serve as "red
      flag" technologies designed to detect areas of abnormality within large surface
      areas. Other technologies serve to characterize areas of visible abnormality,
      offering a higher spatial resolution to confirm/exclude the presence of
      neoplasia. This review summarizes several available and evolving imaging
      technologies used in the endoscopic diagnosis and surveillance of Barrett's
      associated neoplasia.

PMID- 22453703
TI  - Can we eliminate soil-transmitted helminth infections in Sri Lanka?

PMID- 22453702
TI  - Forkhead family transcription factor FoxO and neural differentiation.
AB  - The Forkhead Box subgroup O (FoxO) transcription factor family is one of the most
      important downstream targets of the phosphatidylinositol 3-kinase/protein kinase
      B signaling pathway playing an important role in many biological functions
      including transcriptional regulation of cellular differentiation. Neuronal
      differentiation is a complex process which involves many signaling pathways and
      molecular mechanisms. Interestingly, recent studies indicate that the FoxO family
      is involved in a number of signaling pathways regulating cell differentiation.
      The actions occur at different stages in the differentiation process and by
      differing mechanisms. This review will focus on FoxO as a novel transcription
      factor in neural differentiation.

PMID- 22453704
TI  - Inadequacy of the risk factor based approach to detect gestational diabetes
      mellitus.
AB  - OBJECTIVE: To evaluate the present risk factor based approach in diagnosis of
      gestational diabetes mellitus (GDM) in Sri Lanka in comparison with new
      guidelines proposed by the International Association of Diabetes and Pregnancy
      Study Groups (IADPSG). METHODS: A community based cross sectional descriptive
      study was conducted among pregnant women with gestational age of 24-28 weeks and
      residing in Anuradhapura district. All eligible pregnant women from selected
      Medical Officers of Health areas were invited to participate. The 75 g oral
      glucose tolerance test was carried out among all participants. RESULTS: According
      to IADPSG criteria, 36 (8.9%) of pregnant women had GDM, compared to 29 (7.2%)
      according to WHO criteria. Prevalence of GDM in the study population (positive by
      one or both methods) was 10.6% (n=43) (95% CI 7.9-13.9%). Of these 43 women,22
      (51.1%) had positive results by both methods. Seven (16.3%) and 14 (32.6%)
      mothers were positive only according to WHO and IADPSG criteria respectively. Out
      of 29 mothers who fulfilled WHO criteria, only one had an abnormal fasting plasma
      glucose, but 28 had abnormal 2 hour values. A total of 170 (42.0%) participants
      had at least one risk factor or early indicator of GDM. A risk based approach
      would have detected only 22 GDM patients according to IADPSG criteria, missing 14
      cases (38.9%) who did not have any of the risk factors for GDM. CONCLUSIONS: The
      risk factor based approach misses more than one third of GDM cases. Urgent
      revision of current GDM screening guidelines is recommended.

PMID- 22453705
TI  - Utility of qualitative methods in a clinical setting: perinatal care in the
      Western Province.
AB  - OBJECTIVE: A peculiar paradox that has been observed in previous studies of
      antenatal care is where patients are satisfied with the services despite obvious
      lack of basic facilities. Qualitative methods were used to describe the
      experience of perinatal care in the Western province with the objective of
      demonstrating application of this method in a clinical setting. METHODS: This
      paper used a 'naturalistic' approach of qualitative methods. In-depth interviews
      conducted with 20 postnatal mothers delivering in tertiary care institutions in
      the Western province was tape recorded, transcribed and content analysed. To
      ensure objectivity and validity of results, the principle investigator received
      only the anonymised data to prevent any prejudices or pre-conceptions affecting
      the results. RESULTS: The main themes emerging from the text demonstrated 'naive
      trust' in the carer and a state of 'hero worship' where patients were distanced
      and therefore unable and unwilling to query the decisions made by the carers.
      This is similar to a state of patient-carer relationship described in a published
      model known as guarded alliance, where the relationship develops though four
      phases based on the level of trust and confidence in the relationship. This state
      explains not only why patients fail to recognise and report any deficiencies in
      the services but also the need for them to justify the behaviour of caregivers
      even when it amounts to incompetence and negligence. CONCLUSIONS: Qualitative
      methods allow the researcher to capture experiences in its 'natural' form rather
      than based on pre-determined protocols or plans, which may be limited to our own
      understanding and expectations and therefore unable to explain many
      idiosyncrasies of the programmes. This paper argues favourably for the use of
      qualitative methods in other clinical settings.

PMID- 22453706
TI  - Direct and indirect cost of schizophrenia in outpatients treated in a tertiary
      care psychiatry unit.
AB  - OBJECTIVE: To estimate the direct and indirect cost of care incurred by patients
      with schizophrenia attending a tertiary care psychiatry unit in Colombo. METHODS:
      Study was carried out at the National Hospital of Sri Lanka. Systematic sampling
      selected every second patient with an ICD-10 clinical diagnosis of schizophrenia
      presenting to the clinic during a two month period. Investigator administered
      semi-structured questionnaire was used for data collection. RESULTS: Sample
      consisted of 91 patients. Direct cost was defined as cost incurred by the patient
      (out of pocket expenditure) for outpatient care. Mean cost of a clinic visit was
      Rs. 500. Of the clinic visit cost, highest proportions were travel cost (39.8%)
      and medication (26.4%). Sixty four (70.3%) had received informal care. The mean
      cost of informal care during the entire course of the illness was Rs. 33, 540.
      Mean indirect cost was Rs. 150,190. CONCLUSIONS: Despite low direct cost of care,
      indirect cost and cost of informal treatment results in substantial economic
      impact on patients and their families. It is recommended that economic support
      should be provided for patients with disabling illnesses such as schizophrenia,
      especially when patients are unable to engage in full time employment. There is a
      need to educate the public regarding higher cost of care by traditional healers
      and other informal modes of treatment compared to Western medical care.

PMID- 22453707
TI  - The effect of a herbal formulation on the incidence and severity of upper
      respiratory symptoms in healthy volunteers: an open-label, randomised controlled
      clinical trial.
AB  - INTRODUCTION: Many traditional preparations with varying combinations of herbs
      have been used for over 1500 years to treat upper respiratory ailments, and
      reduce their incidence and severity. Link Samahan(r) is a formulation containing
      the extract of 14 such medicinal plants. OBJECTIVES: To test the efficacy of Link
      Samahan(r) in reducing the incidence and severity of upper respiratory symptoms
      in consenting healthy volunteers. SETTING: MAS Linea Aqua, a factory with over
      3000 employees, having its own health care centre with a qualified matron and
      visiting medical officers. METHODS: 956 healthy volunteers took daily either one
      sachet of Link Samahan(r) in hot water (test group,n=465, mean age 29.5 +/- 7.7
      years, women 418) or only plain tea (control group n=491, mean age 29.7 +/- 7.9,
      women 448), for 84 consecutive days, and recorded the incidence and severity of
      15 upper respiratory symptoms daily in a purpose-designed form. RESULTS: At the
      end of 84 days, when compared to the control group, the average incidence of
      symptoms in the test group showed highly significant reductions at p<0.001 for 6
      symptoms and at p<0.005 for 3 symptoms,and at p<0.05 for the remaining 6.
      Reduction of average incidence over time also was highly significant (p<0.001)
      for 2 symptoms and (p<0.005) for 7, and significant (p<0.05) for 4 symptoms, but
      only marginal for the balance 2. Severity was significantly reduced (p<0.05) for
      7 symptoms, and reduced also for the other 8 according to descriptive analysis,
      though not significant at the 5% level. CONCLUSIONS: The results indicate that
      Link Samahan(r) taken as one sachet daily significantly reduces average
      incidence, incidence over time, and severity of 15 upper respiratory symptoms in
      healthy adults.

PMID- 22453708
TI  - A comparison of endoanal ultrasound and computed tomography in staging rectal
      cancer and in clinical decision making - a preliminary study.
AB  - INTRODUCTION: The treatment options and the prognosis of rectal cancer (RC)
      depend mainly on the stage. Computed tomography (CT) has been the main staging
      tool in RC but endoanal ultrasound (EAUS) is thought to be more accurate.
      METHODS: Patients with histologically proven rectal cancer presenting for the
      first time were staged using CT and EAUS. TNM staging was used to stage the
      rectal cancer. RESULTS: 24 patients (M:F 1:1) with a mean age of 57.3 (range = 23
      80, SD = 15.3) years were included. The majority had a tumour of stage IIA/T3N0M0
      (CT = 10, EAUS = 12). The staging of the tumour was the same in both
      investigations in 11 patients, while in 8 patients, EAUS staging was higher. The
      agreement for the T and N stages were kappa 0.24 and 0.5 respectively. There was
      a moderate and fair agreement between the overall TNM staging (weighted kappa
      0.435) and the treatment strategies (weighted kappa 0.226) respectively, based on
      each imaging method. Of the 13 patients whose staging was different, the
      management changed in 6 (25%) patients (p = 0.016). CT identified distal
      metastases in 2 patients. CONCLUSIONS: EAUS and CT have only a fair to moderate
      agreement for staging and deciding treatment. However,EAUS has a significant
      influence when deciding treatment protocols.

PMID- 22453709
TI  - Conservative approach to the management of morbidly adherent placentae.
AB  - OBJECTIVE: To determine the effect of conservative management of morbidly
      adherent placentae on maternal morbidity and mortality and to review management
      options METHODS: All case notes of patients with placenta accreta and percreta
      between June 2008 and August 2010 were studied retrospectively. RESULTS: Eight
      placentae percretae and 4 placentae accretae were identified out of a total of
      11,358 deliveries.All 12 patients underwent caesarean section. Placentae
      percretae were intentionally left in situ. Interventional radiology was used in
      these cases. There was one emergency hysterectomy for massive obstetric
      haemorrhage,one case of disseminated intravascular coagulation,one case of early
      sepsis and 3 cases of delayed sepsis.Average blood loss was 2490 ml with the mean
      volume transfused being 1425 ml. The mean hospital stay was 7 days and 2 patients
      were admitted to intensive care. One patient was readmitted with sepsis
      complicated by a utero-cutaneous fistula (complete placenta praevia).Another
      patient required re-embolisation 5 months post delivery for persistent
      haemorrhage. No ureteric or bladder injuries occurred. CONCLUSIONS: Conservative
      management of placenta percreta is an alternative to caesarean hysterectomy. It
      is associated with lower maternal morbidity rates.However, monitoring for sepsis
      and secondary postpartum haemorrhage is essential. Rare complications such as
      utero-cutanus fistulae may occur.

PMID- 22453710
TI  - Posterior reversible encephalopathy syndrome as the first manifestation of
      chronic kidney disease.

PMID- 22453711
TI  - A Sri Lankan infant with vaccine associated acute flaccid paralysis.

PMID- 22453712
TI  - An infant with massive haemobilia due to cavernous transformation of the portal
      vein.

PMID- 22453713
TI  - Thrombotic microangiopathy and fibrinolysis after hump-nosed viper envenomation.

PMID- 22453714
TI  - Rapid onset obesity, hypoventilation, hypothalamic, autonomic and thermal
      dysregulation, and neural tumour (ROHHADNET) syndrome presenting with Cushing
      syndrome.

PMID- 22453715
TI  - A case series of domestic pressure cooker burns.

PMID- 22453716
TI  - A descriptive study on self-poisoning in Ampara.

PMID- 22453717
TI  - Determinants of and interventions for malnutrition.

PMID- 22453718
TI  - Utility of three-dimensional echocardiography for assessment of double-orifice
      mitral valve.

PMID- 22453719
TI  - Saccade performance in the nasal and temporal hemifields.
AB  - There are numerous asymmetries in anatomy between the nasal and temporal
      hemiretinae, which have been connected to various asymmetries in behavioral
      performance. These include asymmetries in Vernier acuity, saccade selection, and
      attentional function, in addition to some evidence for latency differences for
      saccadic eye movements. There is also evidence for stronger retinotectal neural
      projection from the nasal than the temporal hemiretina. There is, accordingly,
      good reason to predict asymmetries in saccadic performance depending on which
      hemifield the saccade trigger stimuli are presented in, but the evidence on this
      is mixed. We tested for asymmetries in both saccade latency and landing point
      accuracy in a variety of different saccade tasks. We found no evidence for any
      asymmetries in saccade latency and only modest evidence for asymmetries in
      landing point accuracy. While this lack of asymmetry is surprising in light of
      previous findings of attentional asymmetries, it may reflect that cortical input
      to midbrain eye control centers mitigates any retinal and retinotectal asymmetry.

PMID- 22453720
TI  - Prevalence of occult anemia in an urban pediatric emergency department: what is
      our response?
AB  - OBJECTIVE: Treating or referring patients who are found to be anemic during
      pediatric emergency department (ED) encounters should lead to improved health in
      children and young adults. Before establishing guidelines how to approach the
      anemic in the pediatric ED, it is essential to determine the prevalence of anemia
      in the ED and our response to the presence of anemia. METHODS: We performed a
      retrospective cross-sectional study on hemoglobin levels from patients 1 to 23
      years evaluated in an inner-city public hospital pediatric ED during a 12-month
      period. The primary outcome measure was the prevalence of prior unknown or
      "occult" anemia, stratified by age, sex, and insurance status. The secondary
      outcome was the proportion of patients with "occult" anemia who had their
      condition diagnosed during their ED encounter. Descriptive data analysis was
      performed. RESULTS: Our study population consisted of 2131 patients who had a
      complete blood count drawn in the ED. Prevalence of "occult" anemia was 13.9%
      (95% confidence interval [CI], 12.5%-15.4%). Proportions among the subpopulations
      were 14.8% (95% CI, 10.0%-19.5%) in preschool children, 16.3% (95% CI, 14.2%
      18.3%) in females, 18.5% (95% CI, 15.4%-21.7%) in the uninsured, and 20.7% (95%
      CI, 16.5%-24.9%) in females of childbearing age without insurance. Only 24
      patients (8%) with "occult" anemia had the condition identified on discharge.
      CONCLUSIONS: Anemia has a high prevalence in this pediatric ED population,
      especially among females of childbearing age and the uninsured. Pediatric
      emergency medicine physicians are missing on an opportunity to address a common
      health problem that is easily corrected with appropriate therapy and outpatient
      follow-up.

PMID- 22453721
TI  - Is pediatric emergency department utilization by pregnant adolescents on the
      rise?
AB  - OBJECTIVES: This study evaluates trends of pregnant adolescents' utilization of
      pediatric emergency departments (PEDs), describes patient demographics, and
      reviews common pregnancy-related conditions seen in the PED. METHODS: This was a
      retrospective cross-sectional study of a large pediatric emergency medicine
      research network database including 11 freestanding PEDs, 3 separate PEDs from a
      site with a general ED, and 8 general EDs that see pediatric patients. Pediatric
      patients (<19 years old) were identified from January 1, 2003, to December 31,
      2007, by any International Classification of Diseases, Ninth Revision pregnancy
      or pregnancy-related condition diagnosis code. Demographic information (age,
      race, payer type) and disposition (admit, discharge home, transfer) were
      recorded. RESULTS: There were 15,190 unique pregnancy-related visits with an
      overall annual growth rate of 2.8% (P = 0.03). There was a statistically
      significant increase in visits to freestanding PEDs (P = 0.02) and separate PED
      from a site with a general ED (P = 0.03), but there was not in the general EDs (P
      = 0.16). The 3 most common pregnancy-related conditions were abdominal pain,
      genitourinary infection, and hemorrhage in early pregnancy. CONCLUSIONS: Pregnant
      adolescents make up a small (<1%) but growing proportion of overall visits to
      PEDs. Future direction should include an evaluation of the educational
      opportunities provided during pediatric residency and pediatric emergency
      medicine fellowship training and, if inadequacies exist, work to develop an
      innovative curriculum for this particular patient population.

PMID- 22453722
TI  - Emergency medical services for children: the New Jersey model.
AB  - Identification of specific facilities within a community for the emergency
      department (ED) treatment of children is a traditional component of Emergency
      Medical Services for Children systems. In such models, these Emergency
      Departments Approved for Pediatrics are the preferred EDs to receive patients
      from Emergency Medical Services providers. This article examines an alternative
      model developed in New Jersey in which every ED in the state is required by
      regulation to meet the standards of a traditional Emergency Departments Approved
      for Pediatrics. The New Jersey model leads to more accessible care and more rapid
      stabilization of children regardless of their mode of delivery to the ED.

PMID- 22453723
TI  - Yield of emergent neuroimaging among children presenting with a first complex
      febrile seizure.
AB  - OBJECTIVES: The objective of this study was to assess the risk of intracranial
      pathology requiring immediate intervention among children presenting with their
      first complex febrile seizure (CFS). DESIGN/METHODS: This is a retrospective
      cohort review of patients 6 to 60 months of age evaluated in a pediatric
      emergency department between 1995 and 2008 for their first CFS. Cases were
      identified using computerized text search followed by manual chart review. We
      excluded patients with a prior history of a nonfebrile seizure disorder or a
      prior CFS, an immune-compromised state, an underlying illness associated with
      seizures or altered mental status, or trauma. Data extraction included age, sex,
      seizure features, prior simple febrile seizures, temperature, family history of
      seizures, vaccination status, findings on physical examination, laboratory and
      imaging studies, diagnosis, and disposition. RESULTS: We identified a first CFS
      in 526 patients. Two hundred sixty-eight patients (50.4%) had emergent head
      imaging: 4 patients had a clinically significant finding: 2 had intracranial
      hemorrhage, 1 had acute disseminated encephalomyelitis, and 1 patient had focal
      cerebral edema (1.5%; 95% confidence interval, 0.5%-4.0%). Assigning low risk to
      patients not imaged and not returning to the emergency department within a week
      of the original visit, the risk of intracranial pathology in our sample was 4
      (0.8%; 95% confidence interval, 0.2%-2.1%) of 526. Three of these 4 patients had
      other obvious findings (nystagmus, emesis, and altered mental status; persistent
      hemiparesis; bruises suggestive of inflicted injury). CONCLUSIONS: Very few
      patients with CFSs have intracranial pathology in the absence of other signs or
      symptoms. Patients presenting with more than one seizure in 24 hours in
      particular are at very low risk.

PMID- 22453724
TI  - Dehydration treatment practices among pediatrics-trained and non-pediatrics
      trained emergency physicians.
AB  - OBJECTIVES: We sought to survey emergency physicians in the United States
      regarding the management of pediatric dehydration secondary to acute
      gastroenteritis. We hypothesized that responses from physicians with dedicated
      pediatric training (PT), that is, board certification in pediatrics or pediatric
      emergency medicine, would differ from responses of physicians with no dedicated
      pediatric training (non-PT). METHODS: An anonymous survey was mailed to randomly
      selected members of the American College of Emergency Physicians and sent
      electronically to enrollees of Brown University pediatric emergency medicine
      listserv. The survey consisted of 17 multiple-choice questions based on a
      clinical scenario depicting a 2-year-old with acute gastroenteritis and moderate
      dehydration. Questions asked related to treatment preferences, practice setting,
      and training information. RESULTS: One thousand sixty-nine surveys were received:
      997 surveys were used for data analysis, including 269 PT physicians and 721 non
      PT physicians. Seventy-nine percent of PT physicians correctly classified the
      scenario patient as moderately dehydrated versus 71% of non-PT physicians (P =
      0.063). Among those who correctly classified the patient, 121 PT physicians (58%)
      and 350 non-PT physicians (68%) would initially hydrate the patient with
      intravenous fluids. Pediatrics-trained physicians were more likely to initially
      choose oral or nasogastric hydration compared with non-PT physicians (P =
      0.0127). Pediatrics-trained physicians were less likely to perform laboratory
      testing compared with the non-PT group (n = 92, 45%, vs n = 337, 66%; P <
      0.0001). CONCLUSIONS: Contrary to established recommendations for the management
      of moderately dehydrated children, significantly more PT physicians, compared
      with non-PT physicians, follow established guidelines.

PMID- 22453725
TI  - Effect of altitude on cerebral oxygenation during pediatric interfacility
      transport.
AB  - OBJECTIVES: The objectives of this study were to determine the usefulness of
      cerebral oxygenation monitoring during interfacility helicopter transport of
      pediatric patients and to determine the effect of changes in altitude during
      transport on cerebral oxygenation readings in pediatric interfacility transport
      patients. METHODS: A convenience sample of pediatric interfacility helicopter
      transport patients were monitored using near-infrared spectroscopy (NIRS)
      technology. Cerebral oxygenation numbers were collected at baseline and at
      cruising altitude in patients on room air, supplemental oxygen, and mechanical
      ventilation. Comparisons among readings were performed to determine the effect of
      changing altitude during helicopter transport on cerebral oxygenation. RESULTS:
      Seventeen pediatric patients were monitored at various altitudes during
      interfacility helicopter transport. When compared collectively, there was no
      difference in NIRS readings at baseline (B) and at altitude (A): B--65.9% (SD,
      9.5%) versus A--65.0% (SD, 9.9%) (P = 0.06). In patients transported at greater
      than 5000 ft above ground level, there was a statistically significant difference
      in NIRS readings: B--69.2% (SD, 8.9%) versus A--66.3% (SD, 9.8%) (P < 0.001).
      Patients requiring mechanical ventilator support also had statistically
      significant differences in NIRS readings above 5000 ft above ground level: B-
      78.1% (SD, 5.9%) versus A--75.0% (SD, 3.5%) (P = 0.01). CONCLUSIONS: Cerebral
      oxygenation monitoring, using NIRS technology, can be used as a monitoring tool
      during pediatric helicopter transport. Cerebral oxygenation may change with acute
      changes in altitude, especially in pediatric patients requiring high levels of
      respiratory support. This technology has the potential to be used to monitor
      tissue oxygenation and possibly guide therapeutic interventions during pediatric
      transport.

PMID- 22453726
TI  - Primary cardiac arrest following sport or exertion in children presenting to an
      emergency department: chest compressions and early defibrillation can save lives,
      but is intravenous epinephrine always appropriate?
AB  - OBJECTIVES: The objective of this study was to describe the characteristics and
      outcome of pediatric patients presenting to an emergency department (ED)
      following out-of-hospital primary cardiac arrest (OHPCA), to determine if long
      term survival is influenced by specific resuscitation interventions. METHODS:
      This was a prospective observational study of cases of OHPCA during sport or
      exertion in young patients presenting to an ED over a 5-year period. Cases were
      identified from a resuscitation database, which documented patient demographics,
      nature of event, emergency treatment, response times, and clinical progress.
      These data were analyzed to determine outcomes. RESULTS: Nine children were
      identified who presented following OHPCA during the study period. The mean age
      was 10.7 (+/-4.2) years. All were subsequently diagnosed with an underlying
      primary cardiac disorder. Six patients (66.6%) survived to make a full recovery.
      All patients who survived had received early chest compressions (within 5
      minutes) and early defibrillation (within 10 minutes). The initial cardiac arrest
      rhythm in all survivors had been an electrically cardiovertable rhythm. Five
      (83%) of the 6 survivors did not receive epinephrine during resuscitation.
      CONCLUSIONS: The importance of early chest compressions and defibrillation in
      collapsed young athletes is highlighted in this report. These interventions can
      result in full long-term neurological recovery. Use of epinephrine in these
      patients may be dangerous. We suggest that special consideration should be given
      to this subgroup of patients in the development of future resuscitation
      guidelines.

PMID- 22453727
TI  - The prevalence of hypoglycemia in children with vomiting or decreased oral intake
      and irritability.
AB  - OBJECTIVE: This study aimed to estimate the prevalence of hypoglycemia in
      children younger than 5 years presenting to the emergency department with
      vomiting or decreased oral intake and irritability. METHODS: Children aged 1
      month to 5 years presenting to the emergency department with vomiting (twice or
      more) or decreased oral intake (>50%) during the past 24 hours and irritability
      as part of the history of present illness were enrolled. Capillary blood glucose
      was obtained at triage. Patients with glucose level higher than 3.0 mmol/L were
      considered normoglycemic. Patients with glucose level of 3.0 mmol/L or lower were
      re-triaged (acuity level increased by 1), and sent to a treatment room with the
      recommendation that our institution's hypoglycemia protocol be applied. RESULTS:
      Of the 145 enrolled patients, 2 were hypoglycemic, for an estimated prevalence of
      1.4%. The mean capillary blood glucose level was 5.4 mmol/L, and the range was
      2.8 to 11.8 mmol/L. The average age of participants was 21 months, and 48.3% were
      female. Most were triaged category 4 or 5, and the most common discharge
      diagnoses were gastroenteritis, viral illness, and vomiting not yet diagnosed.
      CONCLUSIONS: Hypoglycemia is a rare occurrence in all-comers younger than 5 years
      with vomiting or decreased oral intake, even with early signs of neuroglycopenia.
      Measuring the capillary glucose is better left to the discretion of the physician
      than as part of triage.

PMID- 22453728
TI  - Is spontaneous pneumothorax really a pediatric problem? A national perspective.
AB  - OBJECTIVES: Research on spontaneous pneumothorax (SP) has focused on management
      strategies in adolescents and adults, yet pediatric population-based data are
      lacking. The objective of this study was to determine the incidence of SP in the
      pediatric population in different age groups. METHODS: This was a retrospective
      analysis of patients aged 0 to 17 years hospitalized with a diagnosis of SP from
      the Healthcare Cost and Utilization Project Kids' Inpatient Database between 1997
      and 2006. Trends of overall incidence and demographic information, including age,
      sex, length of stay, associated procedures, and associated conditions, were
      obtained and analyzed. RESULTS: The overall incidence of SP in children younger
      than 18 years increased from 2.68 per 100,000 population in 1997 to 3.41 per
      100,000 in 2006. Average age (15.1 years; SE, 0.1 years), age distribution (83% =
      15-17 years old), and hospital length of stay (4.7 days; SE, 0.1 days) remained
      constant. Between 1997 and 2006, males rose from 3.7 times to 4.2 times as likely
      to develop SP as females. In 2006, 70% of all hospitalized SP patients had
      therapeutic procedures documented: chest tube (32%), bleb excision (20%), and
      thoracotomy (8%) were the most common. Emphysematous bleb (21%), asthma (10%),
      and tobacco use (4%) were the most common associated diagnoses in 2006.
      CONCLUSIONS: Although uncommon in children, SP appears to be primarily a
      condition of males and adolescents and appears to be increasing in incidence in
      this population. According to these data, a large portion of children are being
      managed without procedural intervention.

PMID- 22453729
TI  - Characteristics of newly immigrated, Spanish-speaking Latinos who use the
      pediatric emergency department: preliminary findings in a secondary migration
      city.
AB  - OBJECTIVE: This study aimed to assess Latino immigrant usage, access, and reason
      for coming to the pediatric emergency department (PED) and clarify parental
      perceptions, barriers, and concerns regarding Latino children's health. METHODS:
      Interviews and questionnaires were verbally administered to a convenience sample
      of newly immigrated (<10 years in the United States) Latino parents of 57
      patients presenting to the PED. RESULTS: Compared with those with higher levels
      of acculturation, Latinos with lower levels of acculturation were more likely to
      use the PED to meet their children's health care needs. It seems that our PED has
      higher usage by Latino families compared with non-Latino families, which may be
      related to the lack of Latino-focused health infrastructure in our city. Once
      these families present to the PED, they do not seem to differ from overall users
      at our ED and nationally with regard to reason for visit. CONCLUSIONS: Similar to
      many other secondary migration hubs across the United States, our city has
      experienced dramatic growth in its Latino population in the last several years.
      Although health care providers anecdotally report increased service to Spanish
      speaking populations, very little is known about the health care experience of
      Latino families in our area. To provide both equal and expert care to Latino
      children in the PED setting, it is essential that providers have this information
      specific to the context in which they work.

PMID- 22453730
TI  - Superior mesenteric artery syndrome in intellectually disabled children.
AB  - OBJECTIVES: Superior mesenteric artery syndrome (SMAS) is a rare cause of small
      intestinal obstruction in pediatric patients. Children with intellectual
      disabilities are a challenging patient population in which to make this
      diagnosis. The goal of this study was to determine the frequency, presenting
      symptoms, and outcomes of SMAS in intellectually disabled and non-intellectually
      disabled children. METHODS: Retrospective chart review of pediatric patients with
      SMAS admitted to Penn State Hershey Children's Hospital between January 1999 and
      July 2010. RESULTS: Sixteen children with SMAS were identified. The majority were
      male (n = 9) and more than two thirds had an intellectual disability (n = 11).
      Presenting symptoms were similar between groups, but 78% (7/9) of intellectually
      disabled patients who had a gastrostomy tube presented with feeding intolerance.
      Although intellectually disabled patients had a higher number of comorbidities
      and the number of health care visits before diagnosis was higher, this did not
      reach statistical significance. There were also no significant differences in
      length of symptoms before diagnosis and amount of weight loss. However, the
      weight-for-age percentiles in intellectual disabled children were significantly
      lower in those without an intellectual disability (9.09 [20.31] vs 48 [20.19],
      respectively, P <= 0.001). Seventy-five percent of patients responded favorably
      to conservative treatment, but 36% (4/11) of intellectually disabled patients
      required multiple treatments before there was an improvement in their condition.
      CONCLUSIONS: Superior mesenteric artery syndrome was found more often in children
      with an intellectual disability. These data highlight the need to consider SMAS
      if there is difficulty tolerating gastrostomy tube feedings in patients with
      weight-for-age percentiles less than 5%.

PMID- 22453731
TI  - Rapid medical assessment: improving pediatric emergency department time to
      provider, length of stay, and left without being seen rates.
AB  - OBJECTIVES: This article aimed to study the impact of a rapid medical assessment
      (RMA) program on patient flow and left without being seen (LWBS) rates in a
      pediatric emergency department (ED). RMA is designed to evaluate and discharge
      uncomplicated patients quickly or initiate diagnostic workup and treatment before
      the patient is placed in an ED bed. METHODS: Rapid medical assessment was
      initiated January 1, 2008 with an assigned midlevel provider. We compared 6
      months of data from January 1 to June 30, 2007 (pre-RMA), to January 1 to June
      30, 2008 (post-RMA). Data studied were obtained from a tracking system and
      include the time to provider, ED length of stay, and the LWBS rate. t Test was
      used to compare results, and chi test was used to compare LWBS rates. RESULTS:
      During the study period, there were 28,360 patients seen in 2007 and 32,053 in
      2008. Time to provider mean time was 80 minutes (median = 57) in 2007 and 53
      minutes (median = 39) in 2008, with a difference of 27 minutes (95% confidence
      interval, 25-28 minutes). Mean length of stay in 2007 was 239 minutes (median =
      220) compared to 181 minutes (median = 162) in 2008, with a difference of 58
      minutes (95% confidence interval, 56-60 minutes). The LWBS rate decreased from 9%
      in 2007 to 3% in 2008 (chi P < 0.01). CONCLUSIONS: Rapid medical assessment is an
      effective way to improve patient flow and reduce the LWBS rate. A decrease in the
      LWBS rate allows the ED to provide health care to these potentially high-risk
      patients.

PMID- 22453732
TI  - Towards an 'oceans systems biology'.

PMID- 22453733
TI  - A regulatory role for repeated decoy transcription factor binding sites in target
      gene expression.
AB  - Tandem repeats of DNA that contain transcription factor (TF) binding sites could
      serve as decoys, competitively binding to TFs and affecting target gene
      expression. Using a synthetic system in budding yeast, we demonstrate that
      repeated decoy sites inhibit gene expression by sequestering a transcriptional
      activator and converting the graded dose-response of target promoters to a
      sharper, sigmoidal-like response. On the basis of both modeling and chromatin
      immunoprecipitation measurements, we attribute the altered response to TF binding
      decoy sites more tightly than promoter binding sites. Tight TF binding to arrays
      of contiguous repeated decoy sites only occurs when the arrays are mostly
      unoccupied. Finally, we show that the altered sigmoidal-like response can convert
      the graded response of a transcriptional positive-feedback loop to a bimodal
      response. Together, these results show how changing numbers of repeated TF
      binding sites lead to qualitative changes in behavior and raise new questions
      about the stability of TF/promoter binding.

PMID- 22453734
TI  - Elevated serum levels of B-cell activating factor in pediatric renal transplant
      patients.
AB  - BACKGROUND: B-cells are increasingly recognized as important players in
      alloimmunity. B cell-activating factor (BAFF) and its receptor BAFF-R are
      essential for B-cell differentiation and survival. Data on BAFF levels in
      pediatric renal transplant (RT) patients are scarce. OBJECTIVE: It is known from
      adult data that elevated BAFF levels correlate with an unfavorable outcome in
      bone marrow and kidney recipients. To analyze this hypothesis in pediatric renal
      transplant patients we performed a cross-sectional analysis of serum BAFF levels,
      lymphocyte surface BAFF-R expression, and clinical variables in a cohort of 43
      pediatric renal transplant patients. METHODS: We studied serum BAFF, CD19+ B-,
      and FoxP3+ regulatory T-cells (Tregs) and BAFF-R expression in 43 children 2.9
      (0.1-12.4) years after RT on maintenance immunosuppression. Twenty-two healthy
      children and 19 children with chronic kidney disease stage 5 (CKD5) served as
      controls. RESULTS: BAFF levels were significantly higher in RT patients than in
      healthy children (1,435+/-574 vs 894+/-189 pg/mL; p<0.0001) whereas numbers of B
      cells and Tregs were significantly lower. BAFF-R expression on B-cells was
      decreased after RT (531+/-334 vs 707+/-257 MFI; p<0.005), BAFF inversely
      correlated with BAFF-R (r=-0.5022, p<0.006), but not with B-cell count. BAFF was
      elevated in CKD5 patients (1,276+/-294 pg/mL). In RT patients BAFF was
      significantly higher in those with eGFR <60 ml/min/1.73m(2) (1,553+/-447 vs
      1,234+/-323 pg/mL; p=0.02). BAFF levels and BAFF-R expression did not correlate
      with HLA antibody status, time after transplantation, age or gender of the
      patients. CONCLUSION: Serum BAFF concentrations were significantly elevated in
      pediatric RT patients. They correlated with decreased BAFF-R expression on CD19+
      B-cells and impaired allograft function. Our findings of a dysregulated BAFF/BAFF
      R axis may be of clinical relevance after renal transplantation and therefore
      underline the importance of further research into BAFF-dependent mechanisms.

PMID- 22453737
TI  - Jozsef Hamori celebrates 80th birthday with fully active scientific life.
      Preface.

PMID- 22453736
TI  - Renovascular hypertension--is it fibromuscular dysplasia or Takayasu arteritis.
AB  - Renovascular hypertension (RVH) can be caused by many different diseases, with
      the most common being fibromuscular dysplasia (FMD) and Takayasu arteritis (TA).
      A strikingly different diagnostic pattern is seen in children with RVH from
      different parts of the world. In Europe and North America, these children are
      mainly diagnosed as having FMD while in Asia and South Africa they will most
      often get a diagnosis of TA. When comparing the clinical diagnosis for FMD and
      TA, it becomes obvious that there is a great deal of overlap between the
      definitions of these two conditions. Different ways to come to the most accurate
      diagnosis using imaging of the blood vessel wall and positron emission tomography
      (PET) will be discussed. How an accurate diagnosis should influence the treatment
      of the children with these conditions will also be addressed.

PMID- 22453735
TI  - Vitamin D status in children with chronic kidney disease.
AB  - BACKGROUND: The role of vitamin D status in patients with renal insufficiency and
      its relation to dietary intake and parathyroid hormone (PTH) secretion is of
      utmost interest given the morbidity and mortality associated with the disordered
      mineral metabolism seen in chronic kidney disease (CKD). METHODS: We conducted a
      cross-sectional study of 100 pediatric patients with a diagnosis of CKD stage 1-5
      at Children's Hospital Boston, measuring blood levels of 25-hydroxyvitamin D
      [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone and
      obtaining data on nutrient intake and other variables related to vitamin D
      status. RESULTS: Subjects ranged in age from 6 months to 18 years, and 60 were
      male, 40 female. Of the 100 patients, 16 % were deficient in 25(OH)D (<= 20
      ng/mL) and another 24 % were insufficient (<= 30 ng/mL), with 40 % in the
      suboptimal range. Serum 25(OH)D and dietary vitamin D intake were not correlated.
      CONCLUSIONS: We found a high prevalence of hyperparathyroidism in early-stage CKD
      and a significant relationship between 25(OH)D and PTH regardless of calcitriol
      level. Our study results support the suggestion that optimization of vitamin D
      levels may provide additional benefit in preventing or improving
      hyperparathyroidism in patients with early CKD and likely remains important as an
      adjunctive therapy in children with advanced CKD.

PMID- 22453738
TI  - A good spirit for all seasons. A few highlights with my friend Joska Hamori.

PMID- 22453739
TI  - Imidazoleacetic acid-ribotide in the rodent striatum: a putative neurochemical
      link between motor and autonomic deficits in Parkinson's disease.
AB  - We have previously demonstrated that imidazole-4-acetic acid-ribotide (IAA-RP) is
      present in the mammalian brain and is an endogenous ligand at imidazoline binding
      sites. In the present study, we used a polyclonal antiserum to visualize IAA-RP
      containing neurons in the rat caudoputamen. We observe IAA-RP-immunostained
      neurons scattered throughout the dorsal and ventral striatum. Most of these cells
      co-localize GABA, but none are parvalbumin-immunoreactive. In contrast,
      approximately 50% of the calbindin D28k-immunopositive striatal neurons co
      localize IAA-RP. Electrophysiological studies using corticostriatal slices
      demonstrated that bath application of IAA-RP reversibly depresses the
      synaptically mediated component of field potentials recorded in the striatum by
      stimulation of cortical axons. Addition of competitive glutamate receptor
      antagonists completely blocks the response, confirming its association with
      glutamatergic transmission. Using paired-pulse stimuli, IAA-RP was shown to
      exert, at least in part, a presynaptic effect, but blockade of GABAA receptor
      mediated transmission did not alter the response. Lastly, we show that this
      effect is attributable to imidazoline-1 receptors, and not to alpha2 adrenergic
      receptors. Since IAA-RP is an endogenous central regulator of blood pressure, and
      cardiovascular dysfunction is a common symptom associated with Parkinson's
      disease (PD), we speculate that IAA-RP-related abnormalities may underlie some of
      the autonomic dysfunction that occurs in PD.

PMID- 22453740
TI  - What makes the prefrontal cortex so appealing in the era of brain imaging? a
      network analytical perspective.
AB  - It is thought that the prefrontal cortex (PFC) subserves cognitive control
      processes by coordinating the flow of information in the cerebral cortex. In the
      network of cortical areas the central position of the PFC makes difficult to
      dissociate processing and the cognitive function mapped to this region,
      especially when using whole brain imaging techniques, which can detect frequently
      activated regions. Accordingly, the present study showed particularly high rate
      of increase of published studies citing the PFC and imaging as compared to other
      fields of the neurosciences on the PubMed. Network measures used to characterize
      the role of the areas in signal flow indicated specialization of the different
      regions of the PFC in cortical processing. Notably, areas of the dorsolateral PFC
      and the anterior cingulate cortex, which received the highest number of
      citations, were identified as global convergence points in the network. These
      prefrontal regions also had central position in the dominant cluster consisted
      exclusively by the associational areas of the cortex. We also present findings
      relevant to models suggesting that control processes of the PFC are depended on
      serial processing, which results in bottleneck effects. The findings suggest that
      PFC is best understood via its role in cortical information processing.

PMID- 22453741
TI  - Accumulation of lipid inclusions in astrocytes of aging human optic nerve.
AB  - We examined age-related changes in the human optic nerve (ON) from 10 postmortem
      donor eye samples (age: 21- to 94-year-old). In aged ON, many axons showed
      paucity of cytoskeleton, and possessed disorganized myelin that remained in the
      extracellular space. Lipid inclusions were detected in glia, as stained by oil
      red O, and these accumulated with aging. To identify and confirm which glial cell
      type possessed lipid inclusions, we performed immunohistochemistry (IHC) and
      transmission electron microscopy (TEM). Comparisons were made from TEM features
      and size of the glia immunolabeled with glial fibrillary acidic protein and
      glutamine synthetase (markers for astrocytes) and 2',3'-cyclic nucleotide 3'
      phosphodiesterase (a marker for oligodendrocytes). It was found that lipid
      inclusions were restricted to the astrocytes having larger perikarya than the
      oligodendrocytes (IHC) and possessing filaments in cytoplasm (TEM). These
      astrocytes also possessed myelin debris and it is thus likely that those
      inclusions originated from degenerated myelin of the ON axons. These data
      indicate that astrocytes play a role in phagocytosis and clearance of
      disorganized myelin in aging human ON.

PMID- 22453742
TI  - Visual cortical responses to the input from the amblyopic eye are suppressed
      during binocular viewing.
AB  - Amblyopia is a visual disorder caused by an anomalous early visual experience. It
      has been suggested that suppression of the visual input from the weaker eye might
      be a primary underlying mechanism of the amblyopic syndrome. However, it is still
      an unresolved question to what extent neural responses to the visual information
      coming from the amblyopic eye are suppressed during binocular viewing. To address
      this question we measured event-related potentials (ERP) to foveal face stimuli
      in amblyopic patients, both in monocular and binocular viewing conditions. The
      results revealed no difference in the amplitude and latency of early components
      of the ERP responses between the binocular and fellow eye stimulation. On the
      other hand, early ERP components were reduced and delayed in the case of
      monocular stimulation of the amblyopic eye as compared to the fellow eye
      stimulation or to binocular viewing. The magnitude of the amblyopic effect
      measured on the ERP amplitudes was comparable to that found on the fMRI responses
      in the fusiform face area using the same face stimuli and task conditions. Our
      findings showing that the amblyopic effects present on the early ERP components
      in the case of monocular stimulation are not manifested in the ERP responses
      during binocular viewing suggest that input from the amblyopic eye is completely
      suppressed already at the earliest stages of visual cortical processing when
      stimuli are viewed by both eyes.

PMID- 22453743
TI  - Regulatory processes of hunger motivated behavior.
AB  - While food intake and body weight are under homeostatic regulation, eating is a
      highly motivated and reinforced behavior that induces feelings of gratification
      and pleasure. The chemical senses (taste and odor) and their evaluation are
      essential to these functions. Brainstem and limbic glucose-monitoring (GM)
      neurons receiving neurochemical information from the periphery and from the local
      brain milieu are important controlling hunger motivation, and brain gut peptides
      have a modulatory role on this function. The hypothalamic and limbic forebrain
      areas are responsible for evaluation of reward quality and related emotions. They
      are innervated by the mesolimbic dopaminergic system (MLDS) and majority of GM
      neurons are also influenced by dopamine. Via dopamine release, the MLDS plays an
      essential role in rewarding-reinforcing processes of feeding and addiction. The
      GM network and the MLDS in the limbic system represent essential elements in the
      neural substrate of motivation.

PMID- 22453744
TI  - Comparison of blood and saliva lactate level after maximum intensity exercise.
AB  - Several studies have described high correlation of salivary and blood lactate
      level during exercise. Measuring the effectiveness and intensity of training,
      lactate concentration in blood, and lately in saliva are used.The aim of our
      study was to evaluate the correlation between the concentration and timing of
      salivary and blood lactate level in endurance athletes and non-athletes after a
      maximal treadmill test, and to identify physiological and biochemical factors
      affecting these lactate levels.Sixteen volunteers (8 athletes and 8 non-athletes)
      performed maximal intensity (Astrand) treadmill test. Anthropometric
      characteristics, body composition and physiological parameters (heart rate, RR
      variability) were measured in both studied groups. Blood and whole saliva samples
      were collected before and 1, 4, 8, 12, 15, 20 min after the exercise test.
      Lactate level changes were monitored in the two groups and two lactate peaks were
      registered at different timeperiods in athletes. We found significant correlation
      between several measured parameters (salivary lactate - total body water,
      salivary lactate - RR-variability, maximal salivary lactate - maximal heart rate
      during exercise, salivary- and blood lactate -1 min after exercise test).
      Stronger correlation was noted between salivary lactate and blood lactate in
      athletes, than in controls.

PMID- 22453745
TI  - The neuroanatomical and ultrastructural organization of statocyst hair cells in
      the pond snail, Lymnaea stagnalis.
AB  - The ultrastructure, neuroanatomy and central projection patterns, including the
      intercellular connections of the statocyst hair cells of the pond snail, Lymnaea
      stagnalis, were studied, applying different intra- and extracellular cellular
      staining techniques combined with correlative light- and electron microscopy.
      Based on the ultrastructure different hair cells could be distinguished according
      to their vesicle and granule content, meanwhile the general organization of the
      sensory neurons was rather uniform, showing clearly separated perinuclear and
      "vesicular" cytoplasmic regions. Following intra- and extracellular labeling with
      fluorescence dyes or HRP a typical, local arborization of the hair cells was
      demonstrated in the cerebral ganglion neuropil, indicating a limited input-output
      system connected to the process of gravireception. Correlative light- and
      electron microscopy of HRP-labeled hair cells revealed both axo-somatic and axo
      axonic output contacts of hair cell varicosities, and input on sensory axons
      located far from the terminal arborizations. Our findings suggest (i) a versatile
      ultrastructural background of hair cells corresponding possibly to processing
      different gravireceptive information, and (ii) the synaptic (or non-synaptic)
      influence of gravireception at different anatomical (terminal, axonal and cell
      body) levels when processed centrally. The results may also serve as a functional
      morphological background for previously obtained physiological and behavioral
      observations.

PMID- 22453746
TI  - Glial cells in the central nervous system of earthworm, Eisenia fetida.
AB  - Glial elements in the central nervous system of Eisenia fetida were studied at
      light- and electron microscopic level. Cells were characterized with the aid of
      toluidine blue, Glial Fibrillary Acidic Protein (GFAP), S100 staining. We
      identified neurilemmal-, subneurilemmal-, supporting-nutrifying- and myelinsheath
      forming glial cells. Both neuronal and non-neuronal elements are S100
      immunoreactive in the CNS. Among glial cells neurilemmal and subneurilemmal cells
      are S100-immunopositive. With the antibody against the S100 protein one band is
      visible at 15 kDa. GFA P-immunopositive supporting-nutrifying glial cells are
      localized around neurons and they often appear as cells with many vacuoles. GFA P
      positive cell bodies of elongated neurilemmal glial cells are also visible.
      Western blot analysis shows a single 57 kDa GFA P immunoreactive band in the
      Eisenia sample. At ultrastructural level contacts between neuronal and glial
      cells are recognizable. Glial cell bodies and their filopodia contain a granular
      and vesicular system. Close contacts between neuronal cell membranes and glial
      filopodia create a special environment for material transport. Vesicles budding
      off glial cell granules move towards the cell membranes, probably emptying their
      content with kiss and run exocytosis. The secreted compounds in return may help
      neuronal survival, provide nutrition, and filopodia may also support neuronal
      terminals.

PMID- 22453747
TI  - Effect of feeding different levels of energy and protein on performance of Aseel
      breed of chicken during juvenile phase.
AB  - A study was conducted to evaluate the effect of feeding different metabolizable
      energy (ME) and crude protein (CP) levels on performance of Aseel chicken during
      0 to 8 weeks of age (Juvenile phase). At 1 day old, 432 chicks were randomly
      distributed into nine groups. Each group had 48 chicks distributed into eight
      replicates with six birds in each. Maize-soybean meal-based diets with three ME
      levels (2,400, 2,600 and 2,800 kcal/kg) and three CP levels (16%, 18% and 20%)
      were fed to birds in a 3 * 3 factorial design. Different ME levels had
      significant effect on body weight gain (BWG), feed intake and feed conversion
      ratio (FCR). Birds fed diet with 2,400 kcal/kg ME had significantly lower BWG (P
      < 0.004), lower shank length (P < 0.0007), higher feed intake (P < 0.0001) and
      poor FCR (P < 0.0001) than those fed diet with either 2,600 or 2,800 kcal/kg ME.
      Energy efficiency ratio was not influenced by ME, CP or their interaction.
      However, protein efficiency ratio was significantly higher at higher ME levels
      and lower at higher CP levels. There was significant effect of ME, CP and their
      interaction on serum protein and cholesterol levels. However, they made no
      significant effect on antibody titre against New Castle disease vaccine. The
      study concluded that provision of 2,600 kcal/kg ME and 16% CP would be ideal for
      optimum growth of Aseel birds during juvenile phase. However, to obtain better
      FCR, feeding Aseel birds with diet having 2,800 kcal/kg ME and 16% CP would be
      ideal.

PMID- 22453748
TI  - Welcome from the president.

PMID- 22453749
TI  - Editor's Introduction to SGS Abstracts 2011.

PMID- 22453752
TI  - Apparent or real water exchange reactions on [Zn(H2O)4(L)](2+).2H2O (L = sp
      nitrogen donor ligands)? A quantum chemical investigation.
AB  - The exchange of a second coordination sphere water molecule in
      [Zn(H(2)O)(4)(L)](2+).2H(2)O (L = HN(3), HCN, FCN, ClCN, BrCN, CH(3)CN,
      (C(4)H(3))CN, PhCN, (CH(3))(3)CCN, CF(3)CN, CCl(3)CN, CHCl(2)CN, and CH(2)ClCN)
      against a coordinated water molecule was studied by quantum chemical calculations
      (RB3LYP/6-311+G**). The complete reaction consists of an associative binding of
      one H(2)O from the second coordination sphere leading to a six-coordinate
      intermediate [Zn(H(2)O)(5)(L)](2+).H(2)O, followed by the dissociation of a water
      molecule to reach the product state [Zn(H(2)O)(4)(L)](2+).2H(2)O. For a real
      water exchange reaction to occur two different transition states have to be
      included, otherwise only an apparent water exchange reaction takes place. For the
      water exchange reaction in [Zn(H(2)O)(4)(L)](2+).2H(2)O, nearly iso-energetic cis
      and trans-orientated transition states are crossed. The gas-phase proton
      affinity of L shows instructive correlations with structural parameters and
      energy gaps for the investigated reactions.

PMID- 22453753
TI  - Recommendations for antiresorptive therapy in postmenopausal patients with breast
      cancer: Marburg AIBL Guideline Evaluation Study (MAGES).
AB  - Postmenopausal women with hormone-receptor-positive breast cancer usually receive
      aromatase inhibitor (AI) therapy at some point in their disease management.
      Accelerated bone loss during AI therapy poses a problem, especially in
      postmenopausal women who may already have age-related osteopenia or several
      fracture-related risk factors. Guidelines and algorithms have been developed to
      identify women at risk for fractures from low bone mineral density and to provide
      recommendations for antiresorptive treatment. However, the factors used to
      calculate fracture risk and the thresholds for antiresorptive treatment vary
      among the current guidelines and algorithms, potentially leading to inconsistent
      recommendations for or against antiresorptive treatment. The present study
      analyzed antiresorptive treatment decisions in a population of postmenopausal
      women with hormone-receptor-positive breast cancer receiving AI therapy using
      five different guidelines/algorithms (World Health Organization Fracture Risk
      Assessment tool [FRAX], expert consensus, German Dachverband Osteologie, American
      Society of Clinical Oncology, and World Health Organization). The consistency of
      a recommendation for antiresorptive treatment among the five methods was low (4
      %). The consistency of a recommendation against antiresorptive treatment among
      the five methods was higher (57 %), but left approximately 40 % of patients with
      an inconsistent recommendation. The consequences of overtreatment (unnecessary
      exposure to adverse events) and undertreatment (increased risk of fractures and
      possibly decreased disease-free survival) make it imperative that the existing
      guidelines and algorithms be improved. Moreover, evidence-based outcomes from
      antiresorptive treatment decisions are required to validate guidelines and
      algorithms.

PMID- 22453755
TI  - A cascade reaction of pyrrole-2-carbaldehyde substituted Morita-Baylis-Hillman
      adducts in the presence of tetrabutylammonium hydroxide or acetate to construct
      aza-heterocycles.
AB  - The phase-transfer catalyst promoted intramolecular transformation of pyrrole-2
      carbaldehyde substituted Morita-Baylis-Hillman adducts has been disclosed,
      providing an efficient way to construct pyrrolo[1,2-a]azepin-7(6H)-one skeletons
      in moderate to good yields (up to 92%) under mild conditions.

PMID- 22453754
TI  - Quality of life in relation to tamoxifen or exemestane treatment in
      postmenopausal breast cancer patients: a Tamoxifen Exemestane Adjuvant
      Multinational (TEAM) Trial side study.
AB  - Tamoxifen and aromatase inhibitors are associated with side effects which can
      significantly impact quality of life (QoL). We assessed QoL in the Tamoxifen
      Exemestane Adjuvant Multinational (TEAM) Trial and compared these data with
      reported adverse events in the main database. 2,754 Dutch postmenopausal early
      breast cancer patients were randomized between 5 years of exemestane, or
      tamoxifen (2.5-3 years) followed by exemestane (2.5-2 years). 742 patients were
      invited to participate in the QoL side study and complete questionnaires at 1
      (T1) and 2 (T2) years after start of endocrine treatment. Questionnaires
      comprised the EORTC QLQ-C30 and BR23 questionnaires, supplemented with FACT-ES
      questions. 543 patients completed questionnaires at T1 and 454 patients (84%) at
      T2. Overall QoL and most functioning scales improved over time. The only
      clinically relevant and statistically significant difference between treatment
      types concerned insomnia; exemestane-treated patients reported more insomnia than
      tamoxifen-treated patients. Discrepancy was observed between QoL issue scores
      reported by the patients and adverse events reported by physicians. Certain QoL
      issues are treatment- and/or time-specific and deserve attention by health care
      providers. There is a need for careful inquiry into QoL issues by those
      prescribing endocrine treatment to optimize QoL and treatment adherence.

PMID- 22453756
TI  - Telephone triage:  diagnosis of candidiasis based upon self-reported vulvovaginal
      symptoms.
AB  - OBJECTIVE: The study aimed to determine which self-reported vulvovaginal symptoms
      are most consistent with candidiasis confirmed by yeast culture and to establish
      guidelines to determine who can be appropriately treated by telephone triage
      versus office examination for women with vulvovaginal symptoms. MATERIALS AND
      METHODS: A retrospective chart review of 105 patients seen in the Saint Louis
      University Vulvar and Vaginal Disorders Specialty Center during a 14-month period
      was performed after institutional review board approval. Patient's age,
      medication use, symptom scores on a Likert rating scale for vaginal/vulvar pain,
      burning, itching, dyspareunia, wet-mount results, and yeast culture results were
      recorded. Differences in the occurrence of vaginal/vulvar symptoms of any
      severity between women with positive and with negative yeast culture results were
      calculated using chi2 and Fisher exact tests. Differences in symptom scores of
      any severity were compared between women with positive and with negative yeast
      culture results using nonparametric Kolmogorov-Smirnov test, owing to a lack of
      normality of the distributions. Sensitivity of 75% or greater and specificity of
      67% or greater were sought for all 9 recorded symptoms. Multiple logistic
      regression analysis was used to determine which symptoms and their cutoff values
      were significant independent predictors of a positive yeast culture result.
      Receiver operating characteristic curve analysis was used to determine the
      efficacy of individual symptoms and combinations of symptoms for predicting a
      positive yeast culture result. A value of p < 0.05 was used to denote statistical
      significance. RESULTS: Four vulvovaginal symptoms met cutoff criteria for
      analysis to predict a positive yeast culture result: vaginal burning, vulvar
      burning, vulvar itching, and clitoral pain. Vaginal burning with a score of 6 or
      greater (p < 0.001) and vulvar itching with a score of 5 or greater (p < 0.05)
      were significant independent predictors of a positive yeast culture result. Women
      with both a vaginal burning score of 6 or greater and a vulvar itching score 5 or
      greater had a positive predictive value of 91.7% (22/24). Vaginal discharge was
      not shown to be predictive of candidiasis. CONCLUSIONS: Diagnosis of candidiasis
      using self-reported vulvovaginal symptoms by telephone triage is difficult. Self
      reported scores for vaginal burning of 6 or greater and for vulvar itching of 5
      or greater are significant indicators of a positive yeast culture result. Vaginal
      discharge was not predictive of a diagnosis of candidiasis. A symptom chart can
      aid office staff in telephone triage of symptomatic women.

PMID- 22453757
TI  - Vascular hamartoma:  an unusual cause of clitoromegaly in an 18-year-old patient.
AB  - OBJECTIVE: Clitoromegaly encountered in clinical practice is more commonly due to
      endocrinopathies either congenital or acquired. However, acquired clitoromegaly
      due to a nonhormonal cause is quite rare. The authors report a case of
      nonhormonal-acquired clitoromegaly in a woman. MATERIALS AND METHODS: This is a
      case report of an 18-year-old patient with slowly increasing swelling in the
      vulval area for the past 6 months. Clinical examination revealed an enlarged,
      soft, nontender clitoris (4 * 2.5 cm), with a lobulated surface. RESULTS: Frozen
      section from clitoral mass showed a benign tumor. Surgical excision of the mass
      was carried out, preserving the glans. Histopathologic examination of the excised
      mass showed congested blood vessels and fibromuscular tissue with free nerve
      endings suggestive of vascular hamartoma of clitoris. CONCLUSIONS: The correct
      diagnosis of clitoromegaly is essential so that suitable therapy is instituted.
      Thus, management of such cases needs a good clinical judgment and a judicious
      individualization of management protocols.

PMID- 22453758
TI  - The immunoexpression of heparanase 2 in normal epithelium, intraepithelial, and
      invasive squamous neoplasia of the cervix.
AB  - OBJECTIVE: Heparanase 2 (HPSE2) is expressed in various tissues, including the
      brain, intestine, prostate, breast, and endometrium. The aim of this study was to
      investigate the role of HPSE2 in cervical carcinogenesis, which has not been
      clarified to date. MATERIALS AND METHODS: The immunoexpression of HPSE2 in normal
      and neoplastic cervical squamous epithelia was determined using a
      semiquantitative (SQ) method and an index of expression (IE) method, using Image
      Lab Software. A total of 230 cervical tissue samples were analyzed and segregated
      into the following diagnostic groups: normal (27.4%), cervical intraepithelial
      neoplasia 1 (CIN 1, 15.2%), CIN 2 (16.5%), CIN 3 (15.2%), and invasive neoplasia
      (25.7%). The mean HPSE2 expression in the normal group was significantly lower
      than that of the other groups individually or combined (p < .001, for all
      combinations). The immunoexpression via the SQ method was significantly greater
      in the CIN 3 group compared with that in the CIN 1 group (p = .02). The mean
      immunoexpression of the high-grade squamous intraepithelial lesion groups was
      significantly greater than those of the normal and low-grade squamous
      intraepithelial lesion groups (p < .001) and lower compared with that of the
      invasive neoplasia group (p < .001). There were no statistically significant
      differences in the immunoexpression of HPSE2 among the different clinical states
      within the invasive neoplasia group. CONCLUSIONS: The SQ method produced a
      greater sensitivity and specificity than did the index of expression method.
      There was a progressive increase in the mean HPSE2 immunoexpression according to
      the severity of the cervical lesion from the low-grade squamous intraepithelial
      lesion group to the invasive neoplasm group, whereas the normal group displayed
      the lowest level of expression. This is a novel study concerning HPSE2 in the
      cervix and cervical cancer carcinogenesis.

PMID- 22453759
TI  - Numerically bridging lamellipodial and filopodial activity during cell spreading
      reveals a potentially novel trigger of focal adhesion maturation.
AB  - We present a novel approach to modeling cell spreading, and use it to reveal a
      potentially central mechanism regulating focal adhesion maturation in various
      cell phenotypes. Actin bundles that span neighboring focal complexes at the
      lamellipodium-lamellum interface were assumed to be loaded by intracellular
      forces in proportion to bundle length. We hypothesized that the length of an
      actin bundle (with the corresponding accumulated force at its adhesions) may thus
      regulate adhesion maturation to ensure cell mechanical stability and
      morphological integrity. We developed a model to test this hypothesis,
      implementing a "top-down" approach to simplify certain cellular processes while
      explicitly incorporating complexity of other key subcellular mechanisms.
      Filopodial and lamellipodial activities were treated as modular processes with
      functional spatiotemporal interactions coordinated by rules regarding focal
      adhesion turnover and actin bundle dynamics. This theoretical framework was able
      to robustly predict temporal evolution of cell area and cytoskeletal organization
      as reported from a wide range of cell spreading experiments using micropatterned
      substrates. We conclude that a geometric/temporal modeling framework can capture
      the key functional aspects of the rapid spreading phase and resultant
      cytoskeletal complexity. Hence the model is used to reveal mechanistic insight
      into basic cell behavior essential for spreading. It demonstrates that actin
      bundles spanning nascent focal adhesions such that they are aligned to the
      leading edge may accumulate centripetal endogenous forces along their length, and
      could thus trigger focal adhesion maturation in a force-length dependent fashion.
      We suggest that this mechanism could be a central "integrating" factor that
      effectively coordinates force-mediated adhesion maturation at the lamellipodium
      lamellum interface.

PMID- 22453760
TI  - Infection of zebrafish embryos with intracellular bacterial pathogens.
AB  - Zebrafish (Danio rerio) embryos are increasingly used as a model for studying the
      function of the vertebrate innate immune system in host-pathogen interactions.
      The major cell types of the innate immune system, macrophages and neutrophils,
      develop during the first days of embryogenesis prior to the maturation of
      lymphocytes that are required for adaptive immune responses. The ease of
      obtaining large numbers of embryos, their accessibility due to external
      development, the optical transparency of embryonic and larval stages, a wide
      range of genetic tools, extensive mutant resources and collections of transgenic
      reporter lines, all add to the versatility of the zebrafish model. Salmonella
      enterica serovar Typhimurium (S. typhimurium) and Mycobacterium marinum can
      reside intracellularly in macrophages and are frequently used to study host
      pathogen interactions in zebrafish embryos. The infection processes of these two
      bacterial pathogens are interesting to compare because S. typhimurium infection
      is acute and lethal within one day, whereas M. marinum infection is chronic and
      can be imaged up to the larval stage. The site of micro-injection of bacteria
      into the embryo determines whether the infection will rapidly become systemic or
      will initially remain localized. A rapid systemic infection can be established by
      micro-injecting bacteria directly into the blood circulation via the caudal vein
      at the posterior blood island or via the Duct of Cuvier, a wide circulation
      channel on the yolk sac connecting the heart to the trunk vasculature. At 1 dpf,
      when embryos at this stage have phagocytically active macrophages but neutrophils
      have not yet matured, injecting into the blood island is preferred. For
      injections at 2-3 dpf, when embryos also have developed functional
      (myeloperoxidase-producing) neutrophils, the Duct of Cuvier is preferred as the
      injection site. To study directed migration of myeloid cells towards local
      infections, bacteria can be injected into the tail muscle, otic vesicle, or
      hindbrain ventricle. In addition, the notochord, a structure that appears to be
      normally inaccessible to myeloid cells, is highly susceptible to local infection.
      A useful alternative for high-throughput applications is the injection of
      bacteria into the yolk of embryos within the first hours after fertilization.
      Combining fluorescent bacteria and transgenic zebrafish lines with fluorescent
      macrophages or neutrophils creates ideal circumstances for multi-color imaging of
      host-pathogen interactions. This video article will describe detailed protocols
      for intravenous and local infection of zebrafish embryos with S. typhimurium or
      M. marinum bacteria and for subsequent fluorescence imaging of the interaction
      with cells of the innate immune system.

PMID- 22453762
TI  - Reversible helix-random coil transition of poly(m-phenylenediethynylene) by a
      rotaxane switch.
AB  - Pendant rotaxane switch-tethering poly(m-phenylene diethynylene) was synthesized
      by the polyoxidative coupling of a rotaxane containing an axle-terminal m
      diethynylbenzene group and an optically active crown ether. The reversible helix
      random coil transition of the polymer was successfully performed by the
      positional switching of the rotaxane wheel.

PMID- 22453764
TI  - New pharmacogenetic test for detecting an HLA-A*31: 01 allele using the
      InvaderPlus assay.
AB  - BACKGROUND & AIMS: Carbamazepine (CBZ) is widely used for the treatment of
      epilepsy and other neurological disorders. However, 3-5% of CBZ-treated
      individuals suffer from cutaneous adverse drug reactions (cADRs). Recently, in a
      genome-wide association study, HLA-A*31:01 has been reported to be a strong
      genetic marker for CBZ-induced cADRs in both Japanese and European populations.
      As most of the available methods for HLA genotyping are laborious, the
      development of a simple and rapid genotyping method for HLA-A*31:01 is desirable
      from the viewpoint of a clinical pharmacogenetic test. METHODS: More than 1700
      sequences for HLA-A alleles were obtained from the MHC database of the National
      Center for Biotechnology Information (dbMHC). Several HLA-A*31:01-discriminating
      single-nucleotide polymorphisms were selected. These SNPs were used for sequence
      specific primer PCR (SSP-PCR) and for the target site of the Invader reaction. By
      combining SSP-PCR with a target-specific Invader reaction, we designed two sets
      of primers/probes for HLA-A*31:01 allele detection. The performance of both sets
      was evaluated using 90 Asian HapMap samples. Further evaluation was carried out
      using another 376 Japanese samples and 90 CEU (European) and 90 YRI (African)
      HapMap samples. RESULTS: Our assay specifically detected an HLA-A*31:01 allele in
      a total of 466 individuals of the Asian population. Furthermore, the assay
      correctly identified HLA-A*31:01-positive carriers from the CEU and the YRI
      population, respectively, implying that the assay has potential for application
      to other ethnic groups. CONCLUSION: We developed a new HLA-A*31:01-detecting
      method by a combination of SSP-PCR with target-specific InvaderPlus technology.
      As our assay is rapid and accurate, it is hoped that this method will be used in
      a pharmacogenetic test in a clinical setting to avoid CBZ-induced cADRs.

PMID- 22453763
TI  - TNF revisited: osteoprotegerin and TNF-related molecules in heart failure.
AB  - The pathophysiological role of tumor necrosis factor (TNF) in myocardial failure
      has been extensively examined in experimental and clinical studies. Recent
      studies suggest that other members of the TNF/TNF receptor superfamily
      (TNFSF/TNFRSF) also may play a pathogenic role in chronic HF. TNF ligands, and in
      particular members of the TNFRSF, are expressed by a wide variety of cells,
      including myocardial cells. By activating the nuclear factor-kappaB (NF-kappaB)
      and death-related pathways, TNF ligands can induce a variety of effects within
      the myocardium, including apoptosis, hypertrophy, inflammation, and extracellular
      matrix remodeling. Among several TNFSF members that have been shown activated in
      HF, the OPG/RANK/RANKL (osteoprotegerin/receptor activator of NF-kappaB/RANK
      ligand) axis may be of importance in the pathogenesis of this disorder through
      different mechanisms. In this paper, we revisited the role of TNFSF/TNFRSF in the
      pathophysiology of HF, possibly representing new targets for therapy as well as
      new biomarkers in this disorder.

PMID- 22453765
TI  - Ex vivo adenoviral vector gene delivery results in decreased vector-associated
      inflammation pre- and post-lung transplantation in the pig.
AB  - Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor
      lung preservation for transplantation. As cellular metabolism is preserved during
      perfusion, it represents a potential platform for effective gene transduction in
      donor lungs. We hypothesized that vector-associated inflammation would be reduced
      during ex vivo delivery due to isolation from the host immune system response. We
      compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted
      adenoviral vector encoding either green fluorescent protein (GFP) or interleukin
      10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was
      transplanted and the post-transplant function assessed. We identified significant
      transgene expression by 12 hours in both in vivo and ex vivo delivered groups.
      Lung function remained excellent in all ex vivo groups after viral vector
      delivery; however, as expected, lung function decreased in the in vivo delivered
      adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL
      1beta levels. Transplanted lung function was excellent in the ex vivo transduced
      lungs and inferior lung function was seen in the in vivo group after
      transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the
      donor lung is superior to in vivo delivery in that it leads to less vector
      associated inflammation and provides superior post-transplant lung function.

PMID- 22453766
TI  - Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic
      contribution of perivascular enzyme flow.
AB  - The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting
      the brain. Absence of beta-hexosaminidase A and B activities in the Sandhoff
      mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD)
      and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant
      adeno-associated viral vectors (rAAV), serotype 2/1, expressing human beta
      hexosaminidase alpha (HEXA) and beta (HEXB) subunits into 1-month-old Sandhoff
      mice gave unprecedented survival to 2 years and prevented disease throughout the
      brain and spinal cord. Classical manifestations of disease, including spasticity
      as opposed to tremor-ataxia-were resolved by localized gene transfer to the
      striatum or cerebellum, respectively. Abundant biosynthesis of beta
      hexosaminidase isozymes and their global distribution via axonal, perivascular,
      and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the
      sustained phenotypic rescue-long-term protein expression by transduced brain
      parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies
      the corrective enzyme. Prolonged survival permitted expression of cryptic disease
      in organs not accessed by intracranial vector delivery. We contend that infusion
      of rAAV into CSF space and intraparenchymal administration by convection-enhanced
      delivery at a few strategic sites will optimally treat neurodegeneration in many
      diseases affecting the nervous system.

PMID- 22453767
TI  - Spherical bullet formation via E-cadherin promotes therapeutic potency of
      mesenchymal stem cells derived from human umbilical cord blood for myocardial
      infarction.
AB  - The beneficial effects of stem cells in clinical applications to date have been
      modest, and studies have reported that poor engraftment might be an important
      reason. As a strategy to overcome such a hurdle, we developed the spheroid three
      dimensional (3D) bullet as a delivery method for human umbilical cord blood
      derived mesenchymal stem cells (hUCB-MSCs) through the maintenance of cell-cell
      interactions without additional xenofactors, cytokines, or matrix. We made
      spheroid 3D-bullets from hUCB-MSCs at 24 hours' anchorage-deprived suspension
      culture. To investigate the in vivo therapeutic efficacy of 3D-bullets, we used
      rat myocardial infarction (MI) model. Transplantation of 3D-bullet was better
      than that of single cells from monolayer culture or from 3D-bullet in improving
      left ventricular (LV) contractility [LV ejection fraction (LVEF) or LV fractional
      shortening (LVFS)] and preventing pathologic LV dilatation [LV end-systolic
      diameter (LVESD) or LV end-diastolic diameter (LVEDD)] at 8 weeks. In the
      mechanism study of 3D-bullet formation, we found that calcium-dependent cell-cell
      interaction was essential and that E-cadherin is a key inducer mediating hUCB-MSC
      3D-bullet formation among several calcium-dependent adhesion molecules which were
      nominated as candidates after cDNA array analysis. In more specific experiments
      with E-cadherin overexpression using adenoviral vector or with E-cadherin
      neutralization using blocking antibody, we found that E-cadherin regulates
      vascular endothelial growth factor (VEGF) secretion via extracellular signal
      regulated kinase (ERK)/v-akt murine thymoma viral oncogene homolog1 (AKT)
      pathways. During formation of spheroid 3D-bullets, activation of E-cadherin in
      association with cell-cell interaction turns on ERK/AKT signaling pathway that
      are essential to proliferative and paracrine activity of MSCs leading to the
      enhanced therapeutic efficacy.

PMID- 22453768
TI  - Integration frequency and intermolecular recombination of rAAV vectors in non
      human primate skeletal muscle and liver.
AB  - The comprehensive characterization of recombinant adeno-associated viral (rAAV)
      integration frequency and persistence for assessing rAAV vector biosafety in gene
      therapy is severely limited due to the predominance of episomal rAAV vector
      genomes maintained in vivo. Introducing rAAV insertional standards (rAIS), we
      show that linear amplification-mediated (LAM)-PCR and deep sequencing can be used
      for validated measurement of rAAV integration frequencies. Integration of rAAV2/1
      or rAAV2/8, following intramuscular (IM) or regional intravenous (RI)
      administration of therapeutically relevant vector doses in nine adult non-human
      primates (NHP), occurs at low frequency between 10(-4) and 10(-5) both in NHP
      liver and muscle, but with no preference for specific genomic loci. High
      resolution mapping of inverted terminal repeat (ITR) breakpoints in concatemeric
      and integrated vector genomes reveals distinct vector recombination hotspots,
      including large deletions of up to 3 kb. Moreover, retrieval of integrated rAAV
      genomes indicated approximately threefold increase in liver compared to muscle.
      This molecular analysis of rAAV persistence in NHP provides a promising basis for
      a reliable genotoxic risk assessment of rAAV in clinical trials.

PMID- 22453769
TI  - Cellular therapy with Ixmyelocel-T to treat critical limb ischemia: the
      randomized, double-blind, placebo-controlled RESTORE-CLI trial.
AB  - Ixmyelocel-T is a patient-specific, expanded, multicellular therapy evaluated in
      patients with lower extremity critical limb ischemia (CLI) with no options for
      revascularization. This randomized, double-blind, placebo-controlled, phase 2
      trial (RESTORE-CLI) compared the efficacy and safety of intramuscular injections
      of ixmyelocel-T with placebo. Patients received one-time injections over 20
      locations in a single leg and were followed for 12 months. Safety assessments
      included occurrence of adverse events. Efficacy assessments included time to
      first occurrence of treatment failure (TTF; major amputation of injected leg; all
      cause mortality; doubling of total wound surface area from baseline; de novo
      gangrene) and amputation-free survival (AFS; major amputation of injected leg;
      all-cause mortality). A total of 77 patients underwent bone marrow or sham
      aspiration; 72 patients received ixmyelocel-T (48 patients) or placebo (24
      patients). Adverse event rates were similar. Ixmyelocel-T treatment led to a
      significantly prolonged TTF (P = 0.0032, logrank test). AFS had a clinically
      meaningful 32% reduction in event rate that was not statistically significant (P
      = 0.3880, logrank test). Treatment effect in post hoc analyses of patients with
      baseline wounds was more pronounced (TTF: P < 0.0001, AFS: P = 0.0802, logrank
      test). Ixmyelocel-T treatment was well tolerated and may offer a potential new
      treatment option.

PMID- 22453770
TI  - A position paper on Physical & Rehabilitation Medicine programmes in post-acute
      settings. Union of European Medical Specialists Section of Physical &
      Rehabilitation Medicine (in conjunction with the European Society of Physical &
      Rehabilitation Medicine).
AB  - Physical & Rehabilitation Medicine (PRM) programmes in post-acute settings cover
      interventions for the rehabilitation of people with a variety of disabling health
      conditions. The setting of the intervention is more important than the timing and
      these programmes can be carried out in a variety of facilities. This paper
      describes the role of PRM services and of PRM specialists in delivering
      rehabilitation programmes to people, who have initially been admitted to
      hospital. The emphasis is on improving patients' activities and addressing
      participation issues. PRM programmes in post-acute settings provide a range of
      treatments and have a major influence in the long-term on the pace and extent of
      return of function and recovery from ill-health. This paper will define the
      meaning of post-acute settings and will describe the patient's journey through
      the post-acute setting. In particular, it addresses the standards of care across
      Europe that patients should expect.  This paper also examines the general
      principles of funding such programmes within the context of different health care
      systems across Europe. Coordinated care improves outcomes and economic profiles
      for both payers and providers of services.  This paper describes the value of PRM
      interventions and PRM specialist-led teams in promoting better outcomes for
      people with disabilities with complex needs.

PMID- 22453771
TI  - The added value of an actuated ankle-foot orthosis to restore normal gait
      function in patients with spinal cord injury: a systematic review.
AB  - OBJECTIVE: To provide an overview of robot-assisted rehabilitation devices
      developed for actuation of the ankle-foot complex and their ability to influence
      the attributes of normal gait in patients with spinal cord injury. METHODS: A
      search was conducted in MEDLINE, Web of Knowledge, National Academic Research and
      Collaborations Information System, and Physiotherapy Evidence Data-base (1985
      2011), using, "ankle", "foot", "robotics", "orthotics" and "spinal cord injury"
      as most relevant keywords. Article inclusion was performed in 3 stages; at the
      level of: (i) title, (ii) abstract and (iii) full text. RESULTS: The actuated
      ankle-foot orthoses currently available are characterized by several combinations
      of an actuator and a control mechanism. Both the actuator and the control
      strategy substantially influence human-machine interaction and therefore the
      potential of the device to assist in modifying locomotor function and potentially
      modify the underlying motor control mechanisms. CONCLUSION: Due to small sample
      sizes, limited studies in patients with spinal cord injury, and limitations in
      study design, it is difficult to draw firm conclusions on the effect of different
      types of actuated ankle-foot orthoses. Based on the limited data available,
      pneumatic artificial muscles in combination with proportional myoelectric control
      are suggested to have the potential to meet most of the preconditions to restore
      the attributes of normal gait and therefore facilitate neuroplasticity.

PMID- 22453773
TI  - Usability testing of two e-learning resources: methods to maximize potential for
      clinician use.
AB  - RATIONALE AND OBJECTIVES: Rigorous usability testing of e-learn-ing resources is
      an important prerequisite to their wide-spread use among clinicians. This study
      demonstrates the application of an evidence-based approach to usability testing
      of two stroke-related e-learning resources (StrokEngine). METHODS: 14 stroke
      rehabilitation clinicians (occupational therapists and physiotherapists) from
      Ontario, Canada participated in a 1.5 h in-person testing session. Clinicians
      navigated StrokEngine in search of information to answer questions on stroke
      assessment/intervention. Their search patterns were observed and clinicians
      provided verbal/written feedback about StrokEngine. Content analysis was used to
      generate themes and categorize them under two broad categories: facilitators and
      barriers to use. RESULTS: Five key facilitators and three key barriers to Strok
      Engine use were identified and related to screen format, layout/organization,
      ease of navigation, quality of content, likelihood of using StrokEngine in the
      future, and system dysfunctions. All 14 clinicians were very or extremely
      satisfied with the layout/organization, quality and clinical relevance of the
      content, stating that they were likely to use StrokEngine in the future.
      CONCLUSION: All identified barriers from this study were addressed with website
      modifications in order to maximize the usability and navigability of StrokEngine.
      This rigorous methodology for usability testing can be applied during the design
      process of any e-learning resource.

PMID- 22453772
TI  - Robot-assisted walking vs overground walking in stroke patients: an evaluation of
      muscle activity.
AB  - OBJECTIVE: There is increasing evidence that robot-assisted treadmill training
      might be useful for gait rehabilitation after stroke. The aim of this study was
      to evaluate the muscle activity of stroke patients during robot-assisted walking
      and overground walking, and of a group of able-bodied subjects during overground
      walking. DESIGN: Case-control observational study. SUBJECTS: Ten stroke subjects
      and 10 able-bodied control subjects. METHODS: Electromyography measurements of 7
      lower-limb muscles were made in 3 trials: robotic walking, in which stroke
      subjects walked in a robot-assisted gait orthosis; overground walking for the
      same group of stroke subjects; and overground walking for control subjects.
      Trials were compared with respect to electromyography amplitude of selected leg
      muscles. RESULTS: Higher muscle activity during overground walking compared with
      robotic walking was found in several muscles during several phases of the gait
      cycle. A significant trial * leg interaction revealed smaller differences in
      muscle activity between the paretic and non-paretic leg during robotic walking
      compared with overground walking. Furthermore, the muscle activity pattern was
      not significantly different between control walking and robotic walking, while it
      was different between control walking and overground walking. CONCLUSION: Despite
      lower muscle activity, robot-assisted treadmill training may elicit a more
      symmetrical pattern of leg muscle activity, which approaches that of able-bodied
      individuals.

PMID- 22453774
TI  - Cough assistance device for patients with glottis dysfunction and/or
      tracheostomy.
AB  - OBJECTIVE: To estimate the efficiency of a cough assistance device, the Cough
      Aid, in patients with weak respiratory muscles with bulbar palsy and/or
      tracheostomy. The Cough Aid is a device that has been developed to substitute for
      glottis function. DESIGN: Before-after trial. SUBJECTS/PATIENTS: A total of 74
      patients with bulbar palsy and/or tracheostomy, as well as respiratory muscle
      weakness, were recruited. METHODS: Forced vital capacity, unassisted cough peak
      flow, lung insufflation capacity, and assisted cough peak flow were measured via
      tracheostomy or oronasal interface. Lung insufflation capacity and assisted cough
      peak flow were measured using the Cough Aid. RESULTS AND CONCLUSION: In all 74
      subjects, lung insufflation capacities measured with the device were
      significantly higher than forced vital capacities (p < 0.01). Assisted cough peak
      flows measured using the device were also significantly higher than unassisted
      cough peak flows (p < 0.01). The Cough Aid is effective in helping to increase
      cough flow and assisting in the air stacking exercise by substituting the
      function of the glottis in patients who have glottis dysfunction or a
      tracheostomy tube.

PMID- 22453775
TI  - Transfer of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)
      from contaminated feed into milk and meat of sheep: pilot study.
AB  - A pilot study was performed with dairy sheep to generate the first data on the
      transfer of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)
      from feed into food of animal origin. Corn silage was cultivated on cropland in
      Lower Saxony in Germany where, as a result of illegal waste disposal in 2006,
      farmland was contaminated with perfluorinated alkylacids (PFAAs). Two sheep were
      exposed by way of PFAA-contaminated corn silage to PFOS (1.16 and 1.45 MUg/kg
      body weight [bw]/d, respectively) and PFOA (0.43 and 0.53 MUg/kg bw/d) during a
      period of 21 days. During the PFAA-feeding period, PFOS levels in plasma
      increased continuously to maximum concentration of 103 and 240 MUg/L for sheep 1
      and sheep 2, respectively. The PFOA plasma concentration remained low (sheep 1 =
      3.3 +/- 2.2 MUg/L; sheep 2 = 15.6 +/- 8.3 MUg/L). Data indicate that urinary
      excretion is the primary clearance route for PFOA (sheep 1 = 51 %; sheep 2 = 55
      %), whereas PFOS excretion by way of urine could not be quantified. The highest
      PFOS excretion (4 to 5 %) was detected in faeces. PFOS was also excreted at
      higher levels than PFOA by way of milk. During a period of 21 days, a total PFOS
      transfer into milk <= 2 % was calculated. Overall, total excretion of PFOS was
      significantly lower compared with that of PFOA (PFOS 6 %; PFOA 53 to 56 %). PFOS
      levels in sheep 1 and sheep 2 were highest in liver (885 and 1,172 MUg/kg weight
      wet [ww], respectively) and lowest in muscle tissue (24.4 and 35.1 MUg/kg ww,
      respectively). PFOA levels in muscle tissue were low for sheep 2 (0.23 MUg/kg ww)
      and not detectable after the PFAA-free feeding period in sheep 1. A slight
      background load of PFOS in liver (1.5 MUg/kg ww) and kidney (0.3 MUg/kg ww) was
      detected in sheep 3 (control).

PMID- 22453776
TI  - A genome-wide comparison of NB-LRR type of resistance gene analogs (RGA) in the
      plant kingdom.
AB  - Plants express resistance (R) genes to recognize invaders and prevent the spread
      of pathogens. To analyze nucleotide binding site, leucine-rich repeat (NB-LRR)
      genes, we constructed a fast pipeline to predict and classify the R gene analogs
      (RGAs) by applying in-house matrices. With predicted ~37,000 RGAs, we can
      directly compare RGA contents across entire plant lineages, from green algae to
      flowering plants. We focused on the highly divergent NBLRRs in land plants
      following the emergence of mosses. We identified entire loss of Toll/Interleukin
      1 receptor, NBLRR (TNL) in Poaceae family of monocots and interestingly from
      Mimulus guttatus (a dicot), which leads to the possibility of species-specific
      TNL loss in other sequenced flowering plants. Using RGA maps, we have elucidated
      a positive correlation between the cluster sizes of NB-LRRs and their numbers.
      The cluster members were observed to consist of the same class of NB-LRRs or
      their variants, which were probably generated from a single locus for an R gene.
      Our website ( http://sol.kribb.re.kr/PRGA/ ), called plant resistance gene analog
      (PRGA), provides useful information, such as RGA annotations, tools for
      predicting RGAs, and analyzing domain profiles. Therefore, PRGA provides new
      insights into R-gene evolution and is useful in applying RGA as markers in
      breeding and or systematic studies.

PMID- 22453779
TI  - A new approved subspecialty.

PMID- 22453777
TI  - Regulation of the polarity of protein trafficking by phosphorylation.
AB  - The asymmetry of environmental stimuli and the execution of developmental
      programs at the organism level require a corresponding polarity at the cellular
      level, in both unicellular and multicellular organisms. In plants, cell polarity
      is important in major developmental processes such as cell division, cell
      enlargement, cell morphogenesis, embryogenesis, axis formation, organ
      development, and defense. One of the most important factors controlling cell
      polarity is the asymmetric distribution of polarity determinants. In particular,
      phosphorylation is implicated in the polar distribution of the determinant
      protein factors, a mechanism conserved in both prokaryotes and eukaryotes. In
      plants, formation of local gradients of auxin, the morphogenic hormone, is
      critical for plant developmental processes exhibiting polarity. The auxin efflux
      carriers PIN-FORMEDs (PINs) localize asymmetrically in the plasma membrane and
      cause the formation of local auxin gradients throughout the plant. The asymmetry
      of PIN distribution in the plasma membrane is determined by
      phosphorylationmediated polar trafficking of PIN proteins. This review discusses
      recent studies on the role of phosphorylation in polar PIN trafficking.

PMID- 22453778
TI  - The mechanism of phloem loading in rice (Oryza sativa).
AB  - Carbohydrates, mainly sucrose, that are synthesized in source organs are
      transported to sink organs to support growth and development. Phloem loading of
      sucrose is a crucial step that drives long-distance transport by elevating
      hydrostatic pressure in the phloem. Three phloem loading strategies have been
      identified, two active mechanisms, apoplastic loading via sucrose transporters
      and symplastic polymer trapping, and one passive mechanism. The first two active
      loading mechanisms require metabolic energy, carbohydrate is loaded into the
      phloem against a concentration gradient. The passive process, diffusion, involves
      equilibration of sucrose and other metabolites between cells through
      plasmodesmata. Many higher plant species including Arabidopsis utilize the active
      loading mechanisms to increase carbohydrate in the phloem to higher
      concentrations than that in mesophyll cells. In contrast, recent data revealed
      that a large number of plants, especially woody species, load sucrose passively
      by maintaining a high concentration in mesophyll cells. However, it still remains
      to be determined how the worldwide important cereal crop, rice, loads sucrose
      into the phloem in source organs. Based on the literature and our results, we
      propose a potential strategy of phloem loading in rice. Elucidation of the phloem
      loading mechanism should improve our understanding of rice development and
      facilitate its manipulation towards the increase of crop productivity.

PMID- 22453780
TI  - Anatomical and histological examination of the porcine vagina and supportive
      structures: in search of an ideal model for pelvic floor disorder evaluation and
      management.
AB  - OBJECTIVE: : The objective of the study was to examine the anatomy and histology
      of the swine vagina and adjacent supportive structures in comparison to human
      tissues to determine the potential utility of this model for pelvic floor
      disorder evaluation and management. METHODS: : This is a descriptive study of the
      gross anatomy and histology of the swine vagina, uterosacral ligament, cardinal
      ligament, and rectovaginal space. Tissue was collected from 6 different sites in
      each of the 6 animals, processed, and stained with hematoxylin-eosin, Masson
      trichrome, and van Gieson and evaluated by both gynecologic and veterinary
      pathologists. RESULTS: : Porcine tissues were similar to the human vagina and
      supporting structures. The origin, insertion, and course of the uterosacral and
      cardinal ligaments appeared similar to those in humans. Histologically, both the
      porcine and human vagina and rectum consist of a mucosal, muscular, and
      adventitial layers. The swine vaginal smooth muscle is arranged in an inner
      circular and outer longitudinal manner. Collagen, elastin, and smooth muscle were
      identified in 5 sites. Collagen was highest in the cardinal compared with the
      uterosacral ligament (P = 0.03), whereas elastin was highest in the uterosacral
      ligament. The vaginal epithelium measured approximately 40 MUm at the vaginal
      cuff and 50 to 200 MUm at anterior and posterior vagina. The swine vagina
      appeared thinner and contained less elastin. The rectovaginal region contained a
      smooth muscle layer leading to a thin adventitial layer. CONCLUSIONS: : The swine
      vagina and adjacent supportive structures appear to be grossly and histologically
      similar to human vaginal anatomy, and these similarities could lead to further
      investigation of the porcine model in the study of pelvic support and support
      disorders.

PMID- 22453781
TI  - A pilot study on vaginally assisted laparoscopic sacrocolpopexy for patients with
      uterovaginal prolapse.
AB  - OBJECTIVES: : The primary objective of this pilot study was to compare the short
      term anatomic outcomes and complication rates of vaginally assisted laparoscopic
      sacrocolpopexy (VALS) with those of conventional laparoscopic sacrocolpopexy (LS)
      in patients undergoing concurrent hysterectomy. The secondary objective was to
      compare operative times of the 2 different techniques. METHODS: : This is a
      retrospective pilot study comparing VALS-a method using transvaginal mesh
      attachment to the vaginal apex-to conventional LS in patients undergoing
      concurrent hysterectomy. RESULTS: : Forty-four women underwent VALS, and 26 women
      underwent LS. There was no significant difference in intraoperative complication
      rates (2.3% vs 3.8%, not statistically significant), postoperative complication
      rates (4.5% vs 0.0%, P = 0.526), mesh extrusion rates (2.3% vs 0%, not
      statistically significant), or postoperative pelvic organ prolapse quantification
      scores. The mean total operative time was 55 minutes shorter for the VALS group
      (215.2 [SD, 41.0] minutes) than the LS group (269.7 [SD, 55.6] minutes; P <
      0.001). CONCLUSIONS: : There was no significant difference in short-term anatomic
      outcomes or complication rates between groups. Vaginally assisted LS was
      associated with significantly shorter operative times than conventional LS.

PMID- 22453782
TI  - Factors associated with urge urinary incontinence after surgery for stress
      urinary incontinence.
AB  - OBJECTIVE: : The objectives of the study were to estimate the severity of urge
      urinary incontinence (UUI) after surgery for stress incontinence and identify
      factors associated with symptom severity. METHODS: : Four hundred thirty-eight
      women who underwent surgery for stress incontinence over a 10-year period
      completed a mailed questionnaire protocol that included validated instruments to
      assess lower urinary tract function and mental and physical well-being. Bivariate
      analysis and generalized linear models were used to identify factors associated
      with severity of UUI as measured by the urge incontinence domain of the
      Incontinence Symptom Index. RESULTS: : Urge urinary incontinence was experienced
      daily by 35.9% of patients. Factors independently associated with higher UUI
      severity scores were preoperative mixed urinary incontinence (P = 0.006),
      depression (P < 0.001), aging (P < 0.001), and longer follow-up times (P = 0.01).
      Pubovaginal sling (P = 0.001) and urethral vaginal suspension (P = 0.04) had
      higher severity scores than Tension-Free Vaginal Tape. CONCLUSIONS: : Daily
      episodes of UUI are experienced by slightly more than one third of women after
      surgery for stress incontinence. Identification of factors associated with UUI
      may help physicians to modify treatment and patient expectations.

PMID- 22453783
TI  - Clinical medical students' self-assessed comfort with technical skills.
AB  - OBJECTIVES: : Medical students spend significant time in the operating room
      during clinical training. Many technical skill domains are learned through trial
      and error, which can affect student confidence and patient safety. This project
      assessed the technical knowledge and comfort of third-year medical students to
      identify their needs for technical skills training before surgical exposure.
      METHODS: : One hundred nine students provided data in an anonymous survey on the
      first day of their core obstetrics/gynecology clerkship. The survey used a 4
      point Likert scale to query self-assessed competence, comfort, and knowledge of
      technical skill domains for the operating room. RESULTS: : Students who rated
      introductory skill domains positively rated themselves higher on complex skill
      domains (2.47 vs 3.75, P < 0.001). Most students (91%) who positively assessed
      complex domains also rated introductory domains positively. There was good
      correlation with comfort in the operating room and the introductory skill domains
      of surgical scrub (0.782) and gowning and gloving (0.784) (P < 0.001).
      CONCLUSIONS: : Students who rate complex domains highly overwhelmingly rate
      introductory skills highly, providing an opportunity to triage technical skill
      knowledge. A focus on introductory skill domains may be beneficial for preparing
      preclinical students for the operating room.

PMID- 22453784
TI  - Randomized trial comparing 2 fiber regimens for the reduction of symptoms of
      constipation.
AB  - OBJECTIVE: : This study aimed to compare the effects of a special bowel recipe
      with psyllium on symptoms of constipation. METHODS: : Women with symptoms of
      constipation were randomized to 6 weeks of either psyllium or a special bowel
      recipe. Patients completed a constipation scoring questionnaire and recorded
      characteristics of each bowel movement. RESULTS: : A total of 53 participants
      completed prestudy and poststudy constipation scoring questionnaires. Both groups
      demonstrated improvement in constipation scores (psyllium: 13.9 +/- 4.7 to 9.0 +/
      4.6, P < 0.001; recipe: 13.6 +/- 4.1 to 8.5 +/- 5.0, P < 0.001). Mean
      differences in pretreatment and posttreatment constipation scores were not
      statistically different between the 2 groups.Subjects taking the bowel recipe
      strained only 20% of the time compared with those using psyllium who strained 57%
      of the time (P = 0.007). Other symptoms improved from baseline, but the majority
      was not different between treatment groups. CONCLUSIONS: : The bowel recipe
      demonstrated no significant difference in efficacy to pure fiber.

PMID- 22453785
TI  - The multicenter urogynecology study on education: associations between
      educational outcomes and clerkship center characteristics.
AB  - OBJECTIVE: : The objective of the study was to examine the effect of center
      characteristics on educational experiences and female pelvic medicine knowledge
      changes in third-year students at 6 medical schools. METHODS: : In this secondary
      analysis of data acquired during a prospective, multicenter study conducted from
      May 2008 through June 2009, preclerkship and postclerkship third-year medical
      students scored their knowledge of 12 female pelvic medicine topics and 4 office
      procedures (knowledge scores [KSs]). Postclerkship, students also reported the
      number and type of learning experiences they had encountered. Participating
      investigators provided data on length of clerkship, number of residents, number
      of fellowship-trained urogynecologists, presence of a fellowship program,
      clerkship grading system type, presence of a urogynecology clerkship rotation,
      and presence of a urogynecology lecture. Analyses used Wilcoxon tests/Spearman
      correlation, with an alpha = 0.05. RESULTS: : Paired preclerkship and
      postclerkship survey data were available for 323 students. Increased numbers of
      learning experiences were positively associated with number of clerkship weeks
      (rs = 0.22, P < 0.001), presence of a urogynecology rotation (P = 0.03), and
      urogynecology lecture (P < 0.001). Knowledge scores were positively associated
      with the number of fellowship-trained urogynecology faculty (rs = 0.17, P =
      0.002) and grading system (letter grades > pass/fail) (P < 0.001). Knowledge
      scores were negatively associated with increasing numbers of residents (rs = 
      0.29, P < 0.001) and presence of a urogynecology fellowship program (P < 0.001).
      The center characteristics of fellowship program and number of residents were
      highly correlated (rs = 0.74, P < 0.001); thus, multivariate modeling was not
      performed. CONCLUSIONS: : The presence of fellowship-trained faculty,
      urogynecology rotation, longer duration of clerkship, and urogynecology lecture
      were positively correlated with higher subjective KSs. The inverse association of
      KS with increased resident number and presence of fellowship was an unexpected
      finding.

PMID- 22453786
TI  - Prospective clinical assessment of the transvaginal mesh technique for treatment
      of pelvic organ prolapse-5-year results.
AB  - OBJECTIVES: : The objective of the study was to assess the effectiveness and
      complication rates for the transvaginal (TVM) technique in the treatment of
      pelvic organ prolapse (POP). METHODS: : Women with symptomatic POP (POP-Q stage
      II-IV) were invited to participate in this institutional review board-approved 5
      year study at 3 US centers. All enrolled patients underwent prolapse repair
      surgery with GYNEMESH PS Prolene Nonabsorbable Soft Mesh using the TVM technique.
      Success was defined as International Continence Society (ICS) POP-Q stage I or
      less. The Prolapse-Specific Inventory and quality-of-life questionnaire was used
      as a subjective outcome measure. RESULTS: : Eighty-five women were included.
      Sixty-six patients were available for follow-up at 5 years. Overall anatomic
      success rates were 88% (90% confidence interval [CI], 80%-93%), 69% (90% CI, 59%
      78%), and 67% (95% CI, 56%-76%) at 1, 3, and 5 years, respectively. Anatomic
      success rates in treated compartments were 89% (90% CI, 82%-94%), 76% (90% CI,
      66%-84%), and 77% (90% CI, 67%-85%) at 1, 3, and 5 years, respectively. When
      defined as treated side leading edge above the hymen, success rates were 89% at 5
      years. Five patients required reoperation for prolapse by 5 years. Statistically
      significant improvements in quality-of-life and Prolapse-Specific Inventory
      scores were sustained over 5 years. Mesh exposure was observed in 16 of 85
      patients over the 5 years. Nine required partial mesh excision. There were 3
      patients with some degree of dyspareunia, reported between 3 and 5 years, whereas
      in 8, preexisting dyspareunia resolved. There was 1 rectovaginal fistula reported
      and 2 reported ureteral injuries, one of which resulted in a ureteral-vaginal
      fistula; all resolved after repair. CONCLUSIONS: : Five-year results indicated
      that TVM provided a stable anatomic repair. Improvements in quality of life and
      associated improvements in specific prolapse symptoms were sustained over the 5
      year period. Mesh exposure was the most common complication.

PMID- 22453787
TI  - Abdominal extraperitoneal excision of a foreign body in the pararectal space.
AB  - Permanent suture material and synthetic grafts can be used as part of pelvic
      organ prolapse surgery. These materials are often attached to the sacrospinous
      ligament or passed in retroperitoneal spaces. There is a risk for erosion and
      granulation tissue formation with any of these materials. Typically, this is
      managed through a transvaginal incision.We present a case of a postmenopausal
      woman with persistent granulation tissue and a sinus tract from a braided
      polyester (Ethibond) suture placed in the right sacrospinous ligament fixation.
      After failing several attempts at treating this granulation tissue through a
      vaginal incision, we managed this via an abdominal retroperitoneal approach.

PMID- 22453788
TI  - Uncomplicated vaginal delivery following midurethral sling.
AB  - BACKGROUND: : Delivery mode following midurethral sling remains controversial.
      There are no formal guidelines as to the preferred mode of delivery following
      midurethral sling. CASE: : A 33-year-old gravida 2 para 2 underwent midurethral
      sling placement 16 months after the delivery of her first child for severe stress
      urinary incontinence (SUI). She conceived 2 months postprocedure and had an
      uneventful antepartum course. She remained without any SUI and delivered via
      uncomplicated spontaneous vaginal delivery at 38 weeks' gestation. One year after
      her delivery, she was still free of SUI symptoms. CONCLUSIONS: : Midurethral
      sling placement may be a valid treatment option for patients with stress
      incontinence even if they are contemplating future pregnancies and subsequent
      vaginal delivery.

PMID- 22453789
TI  - Spontaneous bladder rupture following cystoscopy with hydrodistention and biopsy
      in a female patient with interstitial cystitis.
AB  - We report a case of remote spontaneous rupture of urinary bladder following
      cystourethroscopy with hydrodistention and a bladder biopsy in a patient with
      interstitial cystitis. This required abdominal exploration with cystorrhaphy.
      This case emphasizes a unique and dangerous complication of this procedure in a
      patient with interstitial cystitis.

PMID- 22453790
TI  - Use of physical therapy to augment dilator treatment for vaginal agenesis.
AB  - OBJECTIVE: : Dilator therapy has been used successfully for many years to treat
      vaginal agenesis. Our objective was to show how established physical therapy
      techniques can be used to augment dilator therapy. METHODS: : A 36-year-old woman
      desiring nonsurgical management of vaginal agenesis was instructed in the use of
      vaginal dilators by a pelvic-floor physical therapist. Manual stretching of the
      vaginal tissues was performed during office visits after application of heat and
      therapeutic ultrasound to the perineum. In addition, the patient's husband was
      taught how to perform the vaginal stretching at home in conjunction with dilator
      therapy. RESULTS: : The patient was able to attempt intercourse after 6 weeks of
      treatment and achieved full penetration by 9 weeks. At the completion of
      treatment, she scored 31.9 on the Female Sexual Function Index. The patient and
      her husband were very satisfied with the treatment approach, especially the
      encouragement and guidance received in physical therapy. CONCLUSIONS: : By using
      established physical therapy techniques in conjunction with dilator therapy, a
      faster time to intercourse may be achieved with high patient and spouse
      satisfaction. We recommend the involvement of a physical therapist specializing
      in the pelvic floor as an adjunct to standard dilator therapy in the treatment of
      vaginal agenesis.

PMID- 22453791
TI  - Elderly falls: a national survey of UK ambulance services.
AB  - OBJECTIVE: To provide a detailed description of the current UK ambulance service
      provision for older people who fall. METHOD: National survey of UK ambulance
      services. RESULTS: 11/13 Ambulance services (84.6%) participated in this national
      survey. CONCLUSION: This survey has highlighted the need for robust evidence to
      inform policy, service and practice development to improve the care of this
      vulnerable population.

PMID- 22453792
TI  - Prevalence and severity of suffering among patients with advanced cancer.
AB  - BACKGROUND: Suffering is an expression commonly used to describe distressing
      experience of cancer patients. Suffering experience among patients with advanced
      cancer has not been studied before in Saudi Arabia. OBJECTIVE: The objective of
      this study is to determine the pattern of suffering and the feasibility of
      measuring its severity on a numerical scale for cancer patients attending a
      palliative care outpatient clinic. METHODS: This is part of a larger survey
      studying the pattern of symptomatology in an outpatient palliative care clinic.
      Over a 5-month period, cancer patients attending an outpatient palliative care
      clinic were requested to rate their suffering as well as 11 listed symptoms on a
      0-10 numerical scale. RESULTS: Of the 124 patients interviewed, 73 (59 %) were
      females. Only 15 patients (12 %) reported no suffering. For those who were
      suffering (88 %), the median score is 5. Suffering scores did not differ based on
      sex, age, or type of cancer. Patients with a Palliative Performance Scale of <=50
      % had significantly higher mean suffering score (6.8) compared to those with
      better performance status (4.8; P = 0.003). Multivariate analysis resulted in
      three independent variables showing a significant relationship to suffering
      score, namely pain (P = 0.018), tiredness (P = 0.022), and depression (P =
      0.022). CONCLUSION: Patients with advanced cancer were able to easily rate their
      suffering on a numerical scale. Pain, tiredness, and depression were associated
      with the suffering scores. Suffering scores might help in tracing the trend of
      suffering in the individual patient over time.

PMID- 22453794
TI  - Mycobacterium fortuitum infection in a renal transplant recipient.

PMID- 22453793
TI  - Immunonutrition before and during radiochemotherapy: improvement of inflammatory
      parameters in head and neck cancer patients.
AB  - PURPOSE: Inflammatory, angiogenic and oxidative stress markers have been explored
      in head and neck squamous cell carcinoma (HNSCC) patients before and during
      radiochemotherapy. Furthermore, the effects of an oral supplementation containing
      amino acids, omega-3 fatty acids, ribonucleic acids, vitamins, and antioxidants
      on biological markers and acute toxicities were investigated. METHODS: Thirty-one
      patients with non-metastatic stage III or IV HNSCC treated with concomitant
      radiochemotherapy were recruited. A nutritional support (Oral Impact) was given
      during 5 days before each cycle of chemotherapy. Biological samples were
      collected at baseline, after 5 days of oral supplementation and before the last
      cycle of chemotherapy. Acute phase proteins levels, proteomic cytokines
      determination and urinary isoprostanes levels were used as inflammatory and
      oxidative stress biomarkers. Toxicities were followed up during
      radiochemotherapy. RESULTS: At baseline, median levels of inflammatory (CRP 9.8
      mg/l [0.8-130.1], IL-6 4.2 pg/ml [0.7-126.5]), pro-angiogenic (VEGF 229.5 pg/ml
      [13.1-595.9]) and pro-oxidative stress (urinary isoprostanes 118 pmol/mmol
      creatinine [51-299]) markers were increased. Decrease in CRP (p = 0.002) and
      alpha-1 acid glycoprotein (p = 0.020) levels were observed after 5 days of oral
      supplementation. During radiochemotherapy, no significant variation of
      inflammatory markers was reported, and a low incidence of severe acute mucositis
      was noted. CONCLUSIONS: Stage III or IV HNSCC patients are characterised by a pro
      inflammatory, pro-angiogenic and pro-oxidative status. Nutritional support could
      improve this inflammatory state and could prevent severe acute mucositis.

PMID- 22453795
TI  - Differential response of three cell types to dual stress of nitric oxide and
      radiation.
AB  - The perception of toxicity to nitric oxide (NO) and irradiation (IR) by three
      different cell types has been studied. The three cell types are the macrophage
      like RAW264.7 cells, EL4 lymphoma cells, and splenocytes, which represent the
      different components of a tumor. These three cell types respond differently to NO
      donors (SNP and SNAP) and radiation treatment. The macrophages were found to be
      most radio-resistant and insensitive to NO donors. The innate resistance of the
      macrophages was not due to its antioxidant defense system since there was no
      significant activation of the enzymes (superoxide dismutases, catalase, and
      glutathione peroxidase) in RAW264.7 cells after NO donor and irradiation. But the
      cell cycle arrest of the three cell types was different from each other. The EL4
      cells were found to arrest in the G2/M phase while the macrophages were found
      arrested in the G1 phase of the cell cycle. Such specific killing of the tumor
      cell in response to NO donor while sparing the macrophages can be of immense
      importance to radiotherapy.

PMID- 22453796
TI  - Histological examination of vascular lesions caused by stent implantation in
      humans and in comparative experimental animal model.
AB  - A comparative analysis of human and experimental animal (canine) tissues was
      performed to characterize and describe cellular and histological responses during
      the processes of newly forming intravascular tissues after stent implantation.
      Routine histological and immunohistochemical evaluation of 20 human samples and 9
      samples from animal models were used one day, one week and one month after the
      stent implantation. After one day of implantation, there was no difference
      between the human and canine peripheral arteries, suggesting a similar cellular
      and histological response in the early phase. In contrast, after one week of
      implantation, during the proliferative phase the repairing human tissue showed
      less intensive production of inflammatory cells and more intensive increase in
      number of vascular cells than did the canine model. In addition, cellular changes
      normally restituted by the end of one month in canine peripheral arteries, but
      vascular cells persisted in human atherosclerotic arteries. In conclusion,
      results of this study suggest differences in both phases of vascular repair in
      the post-stented period, because both proliferative and regressive phases showed
      histological differences in canine and human samples. In canine, the restitution
      of vascular wall was completed by the end of first month but persistent vascular
      cell proliferation was visible in the human peripheral arteries. It can be
      suggested that delayed cellular response might indicate restenosis but also can
      be considered considered as a progression of the original arterial disease.

PMID- 22453797
TI  - Expression analysis of heat shock genes in the skin, spleen and blood of common
      carp (Cyprinus carpio) after cadmium exposure and hypothermia.
AB  - Heat shock proteins are chaperones that play a pivotal role in controling
      multiple regulatory pathways such as stress defense, hormone signaling, cell
      cycle control, cell proliferation and differentiation, and apoptosis. In this
      study, the expression patterns of four well-known heat shock genes (hsp70, hsc70
      1, hsc70-2 and hsp90alpha) were characterized in the skin, spleen and blood cells
      of the common carp, under unstressed conditions and after Cd2+ treatment or
      hypothermia. The examined genes were expressed in a tissue-specific manner: hsc70
      2 was expressed constitutively, and was at best only slightly inducible;
      hsp90alpha exhibited a high basic expression in all three tissues, whereas hsc70
      1 did so only in the blood cells, the expression of hsp70 proved to be below the
      level of detection in unstressed fish. Cold shock induced the expression of hsp
      genes in the spleen (hsp90alpha) and blood cells (hsp70, hsc70-1 and hsp90alpha),
      while Cd2+ treatment has no effect on the expression pattern. The highest
      inducibilities were detected in the skin: for hsp70 an induction of at least 20
      fold after cadmium exposure, for hsc70-1 of at least 30-fold and for hsp90alpha
      of 3-fold after hypothermia.

PMID- 22453798
TI  - 3.6-KB mouse cyclin C promoter fragment is predominantly active in the testis.
AB  - Cyclin C is a highly conserved protein that regulates cell-cycle, messenger RNA
      transcription and cell adhesion. Recently published studies demonstrate that this
      protein is an essential player during early embryonic development of
      multicellular eukaryotes as well. In order to understand better its complex
      function at the level of tissues or organs, spatial expression characteristics of
      cyclin C and regulatory components of its expression are needed to be determined.
      In vitro studies on human cells suggested that approximately the first 3
      kilobases of the cyclin C promoter might contain all the regulatory elements that
      might mimic transcription of cyclin C. To test the hypothesis, we generated
      reporter transgenic lines where the first 3.6-kilobase region of mouse cyclin C
      promoter fragment drives the transcription of a marker gene. Messenger RNA levels
      of the marker gene and cyclin C isoforms were measured in nine organs with
      reverse transcription coupled quantitative realtime polymerase chain reaction and
      their expression patterns were compared. The marker gene is predominantly
      transcribed in testes and does not follow the transcriptional regulation of the
      examined cyclin C isoforms. Thus, the isolated promoter fragment alone is not
      sufficient for the complete physiological modulation of cyclin C RNA levels,
      however, it is capable of enhancing testicular transcription which can be
      exploited in future applications.

PMID- 22453799
TI  - In vivo direct interaction of the antibiotic primycin on a Candida albicans
      clinical isolate and its ergosterol-less mutant.
AB  - Interaction of primycin antibiotic with plasma membrane, and its indirect
      biological effects were investigated in this study. The antifungal activity of
      primycin against 13 human pathogenic Candida ATCC and CBS reference species and
      74 other Candida albicans clinical isolates was investigated with a microdilution
      technique. No primycin-resistant strain was detected. Direct interaction of
      primycin with the plasma membrane was demonstrated for the first time by using an
      ergosterol-producing strain 33erg+ and its ergosterol-less mutant erg-2. In
      growth inhibition tests, the 33erg+ strain proved to be more sensitive to
      primycin than its erg-2 mutant, indicating the importance of the plasma membrane
      composition in primycin-induced processes. The 64 MUg ml-1 (56.8 nM) primycin
      treatment induced an enhanced membrane fluidity and altered plasma membrane
      dynamics, as measured by steady-state fluorescence anisotropy applying a
      trimethylammonium-diphenylhexatriene (TMA-DPH) fluorescence polarization probe.
      The following consequences were detected. The plasma membrane of the cells lost
      its barrier function, and the efflux of 260-nm-absorbing materials from treated
      cells of both strains was 1.5-1.8 times more than that for the control. Depending
      on the primycin concentration, the cells exhibited unipolar budding, pseudohyphae
      formation, and a rough cell surface visualized by scanning electron microscopy.

PMID- 22453800
TI  - Ultrastructural aspects and programmed cell death in the tapetal cells of
      Lathyrus undulatus Boiss.
AB  - Programmed cell death (PCD) in the tapetum of Lathyrus undulatus L. was analyzed
      based on light, fluorescence and electron microscopy to characterize its spatial
      and temporal occurrence. Development and processes of PCD in secretory tapetal
      cells of Lathyrus undulatus L. were correlated with the sporogenous cells and
      pollen grains. At early stages of development the tapetal cells appeared similar
      to pollen mother cells, structurally. Concurrent with meiosis, tapetum expanded
      both tangentially and radially as vacuoles increased in size. Tapetal cells most
      fully developed at young microspore stage. However, tapetum underwent substantial
      changes in cell organization including nucleus morphology monitored by DAPI. The
      TUNEL staining confirmed the occurrence of intra-nucleosomal DNA cleavage. In
      addition to nuclear degeneration which is the first hallmark of PCD other
      diagnostic features were observed at vacuolated microspore stage intensely; such
      as chromatin condensation at the periphery of the nucleus, nuclear membrane
      degeneration, chromatin release to the cytoplasm, vacuole collapse according to
      tonoplast rupture, shrinkage of the cytoplasm, the increase and enlargement of
      the endoplasmic reticulum cisternae and disruption of the plasma membrane. After
      vacuole collapse due to possible release of hydrolytic enzymes the cell
      components degraded. Tapetal cells completely degenerated at bicellular pollen
      stage.

PMID- 22453801
TI  - Effect of tropospheric ozone on morphological characteristics of Nicotiana
      tabacum L., Phaseolus vulgaris L. and Petunia*Hybrida L. in ambient air
      conditions.
AB  - The cumulative ozone effect on morphological parameters (visible leaf injury,
      plant height and leaf growth, number of bean pods, petunia flowers and stalks)
      was examined in this study. Well-known ozonesensitive (Bel W3) and ozone
      resistant (Bel B) tobacco cultivars as well as bean cv. Nerina and petunia cv.
      White cascade, both recognized as ozone sensitive, were used in the experiment.
      Investigations were carried out at two exposure sites varying in tropospheric
      ozone levels. Ozone negatively affected the leaf growth of both tobacco cultivars
      and bean. A negative relation was also found for ozone concentration and tobacco
      plant height. Number of petunia flowers and stalks and bean pods was positively
      correlated with ozone concentration. This could have been connected with earlier
      plant maturation due to faster generative development of plants in ozone-stress
      conditions.

PMID- 22453802
TI  - Essential oil composition and preliminary molecular study of four Hungarian
      Thymus species.
AB  - Chemical and genetic differences of twenty taxa belonging to four Thymus species
      were studied in order to determine whether molecular characters and essential oil
      components could be used as taxonomic markers and to examine the correlation
      between them. Plant samples, representing different taxa and geographic regions,
      were collected from experimentally grown populations. Essential oil samples were
      analysed by GC/MS and cluster analysis of volatile composition resulted in
      segregation of thymol chemotypes from sesquiterpenic ones. Thymol was
      characteristic for all the populations of Thymus glabrescens and T. pannonicus as
      well as for certain taxa belonging to T. praecox and T. pulegioides.
      Sesquiterpenes occurred in only two taxa of T. glabrescens, in each sample of T.
      praecox and in three taxa of T. pulegioides. Plant samples were analysed by
      random amplified polymorphic DNA (RAPD). The obtained dendrogram revealed high
      gene diversity. The 13 primers resulted 114 polymorphic RAPD bands, and the
      average percentage of polymorphism was 80.8%. The RAPD dendogram showed
      separation neither at interspecific nor at interpopulational levels. Therefore,
      further specific molecular studies involving more taxa are suggested. Partial
      correlation have been found between molecular and chemical assessments.

PMID- 22453803
TI  - Involvement of source-sink relationship and hormonal control in the response of
      Medicago ciliaris - Sinorhizobium medicae symbiosis to salt stress.
AB  - In order to explore the relationship between leaf hormonal status and source-sink
      relations in the response of symbiotic nitrogen fixation (SNF) to salt stress,
      three major phytohormones (cytokinins, abscisic acid and the ethylene precursor 1
      aminocyclopropane-1-carboxylic acid), sucrose phosphate synthase activity in
      source leaves and sucrolytic activities in sink organs were analysed in two lines
      of Medicago ciliaris (salt-tolerant TNC 1.8 and salt-sensitive TNC 11.9). SNF
      (measured as nitrogenase activity and amount of N-fixed) was more affected by
      salt treatment in the TNC 11.9 than in TNC 1.8, and this could be explained by a
      decrease in nodule sucrolytic activities. SNF capacity was reflected in leaf
      biomass production and in the sink activity under salinity, as suggested by the
      higher salt-induced decrease in the young leaf sucrolytic activities in the
      sensitive line TNC 11.9, while they were not affected in the tolerant line TNC
      1.8. As a consequence of maintaining sink activities in the actively growing
      organs, the key enzymatic activity for synthesis of sucrose (sucrose phosphate
      synthase) was also less affected in the mature leaves of the more tolerant
      genotype. Ours results showed also that the major hormone factor associated with
      the relative tolerance of TNC 1.8 was the stimulation of abscisic acid
      concentration in young leaves under salt treatment. This stimulation may control
      photosynthetic organ growth and also may contribute to a certain degree in the
      maintenance of coordinated sink-source relationships. Therefore, ABA may be an
      important component which conserves sucrose synthesis in source leaves.

PMID- 22453804
TI  - In vitro growth and organogenesis of Prosopis farcta plantlets (Fabaceae,
      Mimosoideae) in culture medium supplemented with various concentrations of Ca++
      and Na+.
AB  - The objective of this study was to vary the mineral composition of the culture
      medium of Prosopis farcta seedlings per addition of Na+ and Ca++ ions with the
      aim to identify the culture media which support the growth and/or the expression
      of the in vitro plant organogenesis. The Na+ and Ca++ ions were added in the
      culture medium in various concentrations by taking the Gamborg medium, in which
      macroelements were diluted 10 times, as the basic one. After two months of
      culture, parameters relating to the vegetative development of plant seedlings and
      to the various expressions of organogenesis were measured. Weak concentrations in
      sodium and calcium ions as well as a weak concentration in Ca++ (0.1 mM) with 50
      mM in Na+ support the best vegetative development of the plantlets. The most
      important percentage of plant seedlings presenting a bud initiation was obtained
      on a medium containing 0.1 mM of Na+ and 50 mM of Ca++. Our study defined several
      media likely to support in vitro development of Prosopis farcta plantlets
      allowing the selection of salt tolerant plants or cellular lines. Some other
      media were chosen for improving micropropagation of the species without adding
      growth substances.

PMID- 22453805
TI  - Genetic and physiological studies on Oenococcus oeni PsuI in response to ethanol
      stress.
AB  - Malolactate fermentation (MLF), which is known to decreases total acidity and
      improves the stability and quality of cider is conducted by Oenococcus oeni; the
      principal microorganism responsible for MLF under stress conditions.
      Understanding O. oeni physiology in stress conditions can be used to generate
      tools based on molecular and physiological approaches allowing more precise
      characterization of strains. Regarding intracellular protein, the results showed
      an increase in the levels of amino acids under ethanol stress. To study the
      expressed genes under ethanol stress, one gene were sequenced. An outer-membrane
      lipoprotein carrier protein precursor, Lo1A was expressed under ethanol stress
      conditions. Scanning electron microscopy was used to study the effect of ethanol
      stress on cell morphology. SEM revealed aggregation of bacterial cells as the
      level of ethanol increases in culture medium in comparison to controls.

PMID- 22453806
TI  - Purification and characterization of a thermostable alpha-galactosidase from
      Thielavia terrestris NRRL 8126 in solid state fermentation.
AB  - Several seeds and husks of some plants belonging to leguminosae, Graminae,
      Compositae and Palmae were evaluated as carbon substrates to produce alpha
      galactosidase (alpha-Gal) by the thermophilic fungus, Thielavia terrestris NRRL
      8126 in solid substrate fermentation. The results showed that Cicer arietinum
      (chick pea seed) was the best substrate for alpha-Gal production. The crude
      enzyme was precipitated by ammonium sulphate (60%) and purified by gel filtration
      on sephadex G-100 followed by ion exchange chromatography on DEAE-Cellulose. The
      final purification fold of the enzyme was 30.42. The temperature and pH optima of
      purified alpha-Gal from Thielavia terrestris were 70  degrees C and 6.5,
      respectively. The enzyme showed high thermal stability at 70  degrees C and 75 
      degrees C and the half-life of the alpha-Gal at 90  degrees C was 45 min. Km of
      the purified enzyme was 1.31 mM. The purified enzyme was inhibited by Ag2+, Hg2+,
      Zn2+, Ba2+, Mg2+, Mn2+ and Fe2+ at 5 mM and 10 mM. Also, EDTA, sodium arsenate, L
      cysteine and iodoacetate inhibited the enzyme activity. On the other hand, Ca2+,
      Cu2+, K+ and Na+ slightly enhanced the enzyme activity at 5 mM while at 10 mM
      they caused inhibition. The molecular weight of the alpha-Gal was estimated to be
      82 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This enzyme
      displays a number of biochemical properties that make it a potentially strong
      candidate for biotechnological and medicinal applications.

PMID- 22453807
TI  - Phylogeny, coat protein genetic variability, and transmission via seeds of Hosta
      Virus X.
AB  - The complete genome of Hosta Virus X (HVX), which is thought to be a distinct
      species of Potexvirus, was sequenced. Nucleotide sequences of HVX were compared
      with those of other members of the genus Potexvirus and phylogenetic tree was
      constructed. The range of identities of viral replicase open reading frame 1
      (ORF1) between HVX and other potexviruses were 43.1%-55.1% and 35.9%-46.6% at the
      nucleotide and amino acid levels, respectively. Phylogenetic analysis was
      performed according to the amino acid sequence of the replicase to determine the
      position of HVX in the genus Potexvirus. Results from the phylogenetic analysis
      demonstrated that HVX was in the same group as Cassava common mosaic virus
      (CsCMV), Plantago asiatica mosaic virus (PlAMV), Tulip virus X (TVX), and
      Hydrangea ring spot virus (HdRSV). In particular, coat protein (CP) sequences
      among viruses from different Hosta cultivars were revealed to be less variable
      than those from different isolates of Potato virus X (PVX), a Potexvirus type
      species. In the present study, HVX was transmissible by seeds of the Hosta "Blue
      Cadet" cultivar. Moreover, HVX was detected in the embryo but not in the seed
      coat or endosperm of the seed.

PMID- 22453808
TI  - A combined micromagnetic-microfluidic device for rapid capture and culture of
      rare circulating tumor cells.
AB  - Here we describe a combined microfluidic-micromagnetic cell separation device
      that has been developed to isolate, detect and culture circulating tumor cells
      (CTCs) from whole blood, and demonstrate its utility using blood from mammary
      cancer-bearing mice. The device was fabricated from polydimethylsiloxane and
      contains a microfluidic architecture with a main channel and redundant 'double
      collection' channel lined by two rows of dead-end side chambers for tumor cell
      collection. The microdevice design was optimized using computational simulation
      to determine dimensions, magnetic forces and flow rates for cell isolation using
      epithelial cell adhesion molecule (EpCAM) antibody-coated magnetic microbeads
      (2.8 MUm diameter). Using this device, isolation efficiencies increased in a
      linear manner and reached efficiencies close to 90% when only 2 to 80 breast
      cancer cells were spiked into a small volume (1.0 mL) of blood taken from wild
      type mice. The high sensitivity visualization capabilities of the device also
      allowed detection of a single cell within one of its dead-end side chambers. When
      blood was removed from FVB C3(1)-SV40 T-antigen mammary tumor-bearing transgenic
      mice at different stages of tumor progression, cells isolated in the device using
      anti-EpCAM-beads and magnetically collected within the dead-end side chambers,
      also stained positive for pan-cytokeratin-FITC and DAPI, negative for CD45-PerCP,
      and expressed SV40 large T antigen, thus confirming their identity as CTCs. Using
      this isolation approach, we detected a time-dependent rise in the number of CTCs
      in blood of female transgenic mice, with a dramatic increase in the numbers of
      metastatic tumor cells appearing in the blood after 20 weeks when tumors
      transition to invasive carcinoma and exhibit increased growth of metastases in
      this model. Importantly, in contrast to previously described CTC isolation
      methods, breast tumor cells collected from a small volume of blood removed from a
      breast tumor-bearing animal remain viable and they can be easily removed from
      these devices and expanded in culture for additional analytical studies or
      potential drug sensitivity testing.

PMID- 22453809
TI  - Optimizing health care delivery by integrating workplaces, homes, and
      communities: how occupational and environmental medicine can serve as a vital
      connecting link between accountable care organizations and the patient-centered
      medical home.
AB  - In recent years, the health care reform discussion in the United States has
      focused increasingly on the dual goals of cost-effective delivery and better
      patient outcomes. A number of new conceptual models for health care have been
      advanced to achieve these goals, including two that are well along in terms of
      practical development and implementation-the patient-centered medical home (PCMH)
      and accountable care organizations (ACOs). At the core of these two emerging
      concepts is a new emphasis on encouraging physicians, hospitals, and other health
      care stakeholders to work more closely together to better coordinate patient care
      through integrated goals and data sharing and to create team-based approaches
      that give a greater role to patients in health care decision-making. This
      approach aims to achieve better health outcomes at lower cost. The PCMH model
      emphasizes the central role of primary care and facilitation of partnerships
      between patient, physician, family, and other caregivers, and integrates this
      care along a spectrum that includes hospitals, specialty care, and nursing homes.
      Accountable care organizations make physicians and hospitals more accountable in
      the care system, emphasizing organizational integration and efficiencies coupled
      with outcome-oriented, performance-based medical strategies to improve the health
      of populations. The ACO model is meant to improve the value of health care
      services, controlling costs while improving quality as defined by outcomes,
      safety, and patient experience. This document urges adoption of the PCMH model
      and ACOs, but argues that in order for these new paradigms to succeed in the long
      term, all sectors with a stake in health care will need to become better aligned
      with them-including the employer community, which remains heavily invested in the
      health outcomes of millions of Americans. At present, ACOs are largely being
      developed as a part of the Medicare and Medicaid systems, and the PCMH model is
      still gathering momentum and evolving among physicians. But, the potential exists
      for implementation of both of these concepts across a much broader community of
      patients. By extending the well-conceived integrative concepts of the PCMH model
      and ACOs into the workforce via occupational and environmental medicine (OEM)
      physicians, the power of these concepts would be significantly enhanced.
      Occupational and environmental medicine provides a well-established
      infrastructure and parallel strategies that could serve as a force multiplier in
      achieving the fundamental goals of the PCMH model and ACOs. In this paradigm, the
      workplace-where millions of Americans spend a major portion of their daily lives
      becomes an essential element, next to communities and homes, in an integrated
      system of health anchored by the PCMH and ACO concepts. To be successful, OEM
      physicians will need to think and work innovatively about how they can provide
      today's employer health services-ranging from primary care and preventive care to
      workers' compensation and disability management-within tomorrow's PCMH and ACO
      models.

PMID- 22453810
TI  - Association of binge eating with work productivity impairment, adjusted for other
      health risk factors.
AB  - OBJECTIVE: This study examined the association between binge eating and
      productivity impairment. METHODS: Using data drawn from individuals completing a
      health risk appraisal and the Work Productivity and Activity Impairment
      questionnaire, analyses examined associations between binge eating and obesity,
      health risks, and productivity impairment. Regression analysis tested
      associations between binge eating and Work Productivity and Activity Impairment
      scores, adjusting for demographics, obesity, and health risks. Unstandardized
      regression coefficients estimated annual productivity loss due to binge eating
      using a hypothetical employer. RESULTS: Significant associations were found
      between binge eating and impairment. Adjusting for demographics, obesity, and
      other risks, binge eating remained a significant correlate of productivity
      impairment. Estimated annual productivity loss due to binge eating in a company
      of 1000 employees was $107,965. CONCLUSIONS: Efforts to reduce productivity
      impairment need to target binge eating as a modifiable risk behavior.

PMID- 22453811
TI  - Association between proinflammatory responses of respirable silica dust and
      adverse health effects among dust-exposed workers.
AB  - OBJECTIVE: To evaluate proinflammatory responses induced by respirable silica
      dust samples and to analyze the role of those responses in explaining adverse
      health effects among dust-exposed workers in pottery factoryies and tungsten and
      tin mines. METHODS: Proinflammatory cytokines of cells were determined after
      being treated with silica dust samples. Adverse health effects of workers were
      calculated on the basis of a cohort study. RESULTS: Incidence and mortality of
      silicosis among tungsten miners were higher than those in other workers. The
      incidence of interleukin-1beta levels was highest in tungsten mines, which was
      consistent with the incidence of silicosis in tungsten miners. The higher levels
      of TNF-alpha and interleukin-6 released from macrophages might be helpful in
      explaining increased mortalities from lung cancer among tin miners. CONCLUSIONS:
      Interleukin-1beta could be a sensitive biomarker in predicting fibrogenic
      potential of silica dust and the risk of silicosis among dust-exposed workers.

PMID- 22453812
TI  - Further validation of the psychological injury risk indicator scale.
AB  - OBJECTIVE: Confirm the Psychological Injury Risk Indicator (PIRI) scale capacity
      to facilitate routine assessment of psychological health of workers in high
      stress environments. METHOD: A cross-sectional study compared the PIRI scale
      scores with two experienced clinical psychologists' assessment of defined
      psychological injury in 93 participants. A second, longitudinal, study assessed
      PIRI predictive capacity for emotional exhaustion, physical health, and work
      engagement in 420 participants over 14 months. RESULTS: The PIRI scale was shown
      to (a) determine the degree of psychological injury in participants with high
      correspondence to a specialist clinical interview; and (b) predict future
      emotional exhaustion, physical health, and work engagement to a significantly
      better degree than the 12-item General Health Questionnaire and Kessler-10
      measures. CONCLUSIONS: The PIRI scale shows a valuable capacity to provide
      accurate routine psychological health assessment for at-risk workers in high
      strain work environments.

PMID- 22453813
TI  - Characteristics associated with health care professional diagnosis of work
      related asthma among individuals who describe their asthma as being caused or
      made worse by workplace exposures.
AB  - OBJECTIVE: To identify factors associated with health care professional-diagnosed
      work-related asthma (WRA) among adults who describe their asthma as being caused
      or made worse by workplace exposures (possible WRA). METHODS: We calculated
      prevalence ratios adjusted for age and sex using data from the 2006 to 2008
      Behavioral Risk Factor Surveillance System Asthma Call-Back Survey from 37 states
      and the District of Columbia for ever-employed adults with current asthma and
      possible WRA. RESULTS: An estimated 17.6% of ever-employed adults with current
      asthma and possible WRA had health care professional-diagnosed WRA. Health care
      professional-diagnosed WRA was associated with age, income, employment status,
      asthma control level, asthma attack, emergency department visit, hospitalization,
      urgent treatment, and changing/quitting a job due to asthma. CONCLUSIONS: Among
      ever-employed adults with possible WRA, health care professional-diagnosed WRA is
      associated with poorer asthma control and frequent unscheduled health care
      visits.

PMID- 22453815
TI  - Hierarchical porous NiCo2O4 nanowires for high-rate supercapacitors.
AB  - We demonstrate a simple and scalable strategy for synthesizing hierarchical
      porous NiCo(2)O(4) nanowires which exhibit a high specific capacitance of 743 F
      g(-1) at 1 A g(-1) with excellent rate performance (78.6% capacity retention at
      40 A g(-1)) and cycling stability (only 6.2% loss after 3000 cycles).

PMID- 22453816
TI  - From the editor.

PMID- 22453817
TI  - Hospital care may not affect the risk of readmission.
AB  - BACKGROUND: : Thirty-day readmissions have become a focal point for reducing
      health care spending, because they are viewed as a marker of the quality of
      hospital care. However, if increased time in the hospital is associated with
      better care, attempts to shorten length of stay (LOS) may result in increased
      rates of readmission. As such, we sought to explore the association of an
      incremental added day in LOS with the rate of readmission. METHODS: : We examined
      the rate of readmission at 30 and 120 days for 4151 patients admitted to a
      general internal medicine unit between July 2004 and March 2006. We used binary
      logistic regression to examine the relationship between an incremental added day
      in LOS and the probability of readmission. RESULTS: : Readmission rates were 8.7%
      at 30 days and 21.0% at 120 days, respectively. After controlling for demographic
      characteristics and severity of illness, we found that the probability of
      readmission varied little for an incremental added day in LOS. CONCLUSIONS: : Our
      findings suggest that more hospital care may not affect the likelihood of
      readmission and thus denying payment for readmission may be unwarranted.

PMID- 22453818
TI  - Evidence-based practice:  cost-benefit of large system implementation.
AB  - The key points for designing and implementing an evidence-based practice (EBP)
      model in a large health care system are discussed. This implementation created
      strategies for practice changes for organizational change. The quality management
      methods included structured EBP toolkits that are described as part of the
      deliverable of each toolkit's Design Team. The cost-benefit evaluation process of
      staff time in the development stage of an EBP is explained. The conclusion is
      that a representative group of clinicians can be leveraged to create the standard
      and materials for system implementation, thereby providing improved patient care
      that is evidence-based and cost-effective.Many hands make light work....

PMID- 22453819
TI  - Revisiting empowerment:  a study of improvement work in health care teams.
AB  - This article reports on a study of team empowerment in a large clinic at a
      Swedish hospital. The focus of the study was to understand how a high degree of
      empowerment enabled the teams to develop and sustain a high level of performance.
      More specifically, a model of empowerment was used to identify important factors
      that contribute to team empowerment in 3 teams at the clinic. In the analysis of
      the empirical data, 21 factors were identified and the degree of empowerment in
      the 3 teams was assessed.

PMID- 22453820
TI  - Perceived organizational problems in health care:  a pilot test of the structured
      problem and success inventory.
AB  - Our objective was to test whether the Structured Problem and Success Inventory
      (SPI) instrument could capture mental representations of organizational and work
      related problems as described by individuals working in health care organizations
      and to test whether these representations varied according to organizational
      position. A convenience sample (n = 56) of middle managers (n = 20), lower-level
      managers (n = 20), and staff (n = 16) from health care organizations in Stockholm
      (Sweden) attending organizational development courses during 2003-2004 was
      recruited. Participants used the SPI to describe the 3 most pressing
      organizational and work-related problems. Data were systematically reviewed to
      identify problem categories and themes. One hundred sixty-four problems were
      described, clustered into 13 problem categories. Generally, middle managers
      focused on organizational factors and managerial responsibilities, whereas lower
      level managers and staff focused on operational issues and what others did or
      ought to do. Furthermore, we observed similarities and variation in perceptions
      and their association with respondents' position within an organization. Our
      results support the need for further evaluation of the SPI as a promising tool
      for health care organizations. Collecting structured inventories of
      organizational and work-related problems from multiple perspectives may assist in
      the development of shared understandings of organizational challenges and lead to
      more effective and efficient processes of solution planning and implementation.

PMID- 22453821
TI  - How team-based reflection affects quality improvement implementation:  a
      qualitative study.
AB  - Quality improvement (QI) interventions in health care organizations have produced
      mixed results with significant questions remaining about how QI interventions are
      implemented. Team-based reflection may be an important element for understanding
      QI implementation. Extensive research has focused on individual benefits of
      reflection including links between reflection, learning, and change. There are
      currently no published studies that explore how team-based reflection impact QI
      interventions. We selected 4 primary care practices participating in a QI trial
      that used a facilitated, team-based approach to improve colorectal cancer
      screening rates. Trained facilitators met with a team of practice members for up
      to eleven 1-hour meetings. Data include audio-recorded team meetings and
      associated fieldnotes. We used a template approach to code transcribed data and
      an immersion/crystallization technique to identify patterns and themes. Three
      types of team-based reflection and how each mattered for QI implementation were
      identified: organizational reflection promoted buy-in, motivation, and feelings
      of inspiration; process reflection enhanced team problem solving and change
      management; and relational reflection enhanced discussions of relational dynamics
      necessary to implement desired QI changes. If QI interventions seek to make
      changes where collaboration and coordination of care is required, then
      deliberately integrating team-based reflection into interventions can provide
      opportunities to facilitate change processes.

PMID- 22453822
TI  - Commentary:  does quality of care include the ability to access and afford health
      care?

PMID- 22453825
TI  - Chemotherapy-related cognitive dysfunction.
AB  - Many cancer patients develop treatment-related cognitive dysfunction that affects
      their quality of life and can result in diminished functional independence. There
      is an emerging body of transdisciplinary research demonstrating that
      chemotherapeutic agents can produce neurobiological changes within the brain,
      which are associated with a constellation of cognitive changes that can result in
      decreased quality of life and functional independence. The increased incidence of
      cancer, coupled with longer survival times, has resulted in larger numbers of
      cancer survivors who are struggling with this neurotoxicity. This review
      summarizes the neuropsychological findings in patients with breast and brain
      cancer who receive systemic chemotherapy as well as the recent animal and imaging
      research elucidating the mechanisms by which these therapies impact brain
      structure, function, and consequent behavior.

PMID- 22453826
TI  - Monitoring the reductive and oxidative half-reactions of a flavin-dependent
      monooxygenase using stopped-flow spectrophotometry.
AB  - Aspergillus fumigatus siderophore A (SidA) is an FAD-containing monooxygenase
      that catalyzes the hydroxylation of ornithine in the biosynthesis of hydroxamate
      siderophores that are essential for virulence (e.g. ferricrocin or N',N",N'''
      triacetylfusarinine C). The reaction catalyzed by SidA can be divided into
      reductive and oxidative half-reactions. In the reductive half-reaction, the
      oxidized FAD bound to Af SidA, is reduced by NADPH. In the oxidative half
      reaction, the reduced cofactor reacts with molecular oxygen to form a C4a
      hydroperoxyflavin intermediate, which transfers an oxygen atom to ornithine.
      Here, we describe a procedure to measure the rates and detect the different
      spectral forms of SidA using a stopped-flow instrument installed in an anaerobic
      glove box. In the stopped-flow instrument, small volumes of reactants are rapidly
      mixed, and after the flow is stopped by the stop syringe, the spectral changes of
      the solution placed in the observation cell are recorded over time. In the first
      part of the experiment, we show how we can use the stopped-flow instrument in
      single mode, where the anaerobic reduction of the flavin in Af SidA by NADPH is
      directly measured. We then use double mixing settings where Af SidA is first
      anaerobically reduced by NADPH for a designated period of time in an aging loop,
      and then reacted with molecular oxygen in the observation cell. In order to
      perform this experiment, anaerobic buffers are necessary because when only the
      reductive half-reaction is monitored, any oxygen in the solutions will react with
      the reduced flavin cofactor and form a C4a-hydroperoxyflavin intermediate that
      will ultimately decay back into the oxidized flavin. This would not allow the
      user to accurately measure rates of reduction since there would be complete
      turnover of the enzyme. When the oxidative half-reaction is being studied the
      enzyme must be reduced in the absence of oxygen so that just the steps between
      reduction and oxidation are observed. One of the buffers used in this experiment
      is oxygen saturated so that we can study the oxidative half-reaction at higher
      concentrations of oxygen. These are often the procedures carried out when
      studying either the reductive or oxidative half-reactions with flavin-containing
      monooxygenases. The time scale of the pre-steady-state experiments performed with
      the stopped-flow is milliseconds to seconds, which allow the determination of
      intrinsic rate constants and the detection and identification of intermediates in
      the reaction. The procedures described here can be applied to other flavin
      dependent monooxygenases.

PMID- 22453827
TI  - Casein kinase 2 reverses tail-independent inactivation of kinesin-1.
AB  - Kinesin-1 is a plus-end microtubule-based motor, and defects in kinesin-based
      transport are linked to diseases including neurodegeneration. Kinesin can auto
      inhibit via a head-tail interaction, but is believed to be active otherwise. Here
      we report a tail-independent inactivation of kinesin, reversible by the disease
      relevant signalling protein, casein kinase 2 (CK2). The majority of initially
      active kinesin (native or tail-less) loses its ability to interact with
      microtubules in vitro, and CK2 reverses this inactivation (approximately
      fourfold) without altering kinesin's single motor properties. This activation
      pathway does not require motor phosphorylation, and is independent of head-tail
      auto-inhibition. In cultured mammalian cells, reducing CK2 expression, but not
      its kinase activity, decreases the force required to stall lipid droplet
      transport, consistent with a decreased number of active kinesin motors. Our
      results provide the first direct evidence of a protein kinase upregulating
      kinesin-based transport, and suggest a novel pathway for regulating the activity
      of cargo-bound kinesin.

PMID- 22453829
TI  - Dark acoustic metamaterials as super absorbers for low-frequency sound.
AB  - The attenuation of low-frequency sound has been a challenging task because the
      intrinsic dissipation of materials is inherently weak in this regime. Here we
      present a thin-film acoustic metamaterial, comprising an elastic membrane
      decorated with asymmetric rigid platelets that aims to totally absorb low
      frequency airborne sound at selective resonance frequencies ranging from 100
      1,000 Hz. Our samples can reach almost unity absorption at frequencies where the
      relevant sound wavelength in air is three orders of magnitude larger than the
      membrane thickness. At resonances, the flapping motion of the rigid platelets
      leads naturally to large elastic curvature energy density at their perimeter
      regions. As the flapping motions couple only minimally to the radiation modes,
      the overall energy density in the membrane can be two-to-three orders of
      magnitude larger than the incident wave energy density at low frequencies,
      forming in essence an open cavity.

PMID- 22453828
TI  - Annexin A2 binds to endosomes following organelle destabilization by particulate
      wear debris.
AB  - Endosomal functions are contingent on the integrity of the organelle-limiting
      membrane, whose disruption induces inflammation and cell death. Here we show that
      phagocytosis of ultrahigh molecular weight polyethylene particles induces damage
      to the endosomal-limiting membrane and results in the leakage of cathepsins into
      the cytosol and NLRP3-inflammasome activation. Annexin A2 recruitment to damaged
      organelles is shown by two-dimensional DIGE protein profiling, endosomal
      fractionation, confocal analysis of endogenous and annexin A2-GFP transfected
      cells, and immunogold labelling. Binding experiments, using fluorescent
      liposomes, confirms annexin A2 recruitment to endosomes containing phagocytosed
      polyethylene particles. Finally, an increase in cytosolic cathepsins, NLRP3
      inflammasome activation, and IL-1 production is seen in dendritic cells from
      annexin A2-null mice, following exposure to polyethylene particles. Together, the
      results indicate a functional role of annexin A2 binding to endosomal membranes
      following organelle destabilization.

PMID- 22453830
TI  - Ultra-low carrier concentration and surface-dominant transport in antimony-doped
      Bi2Se3 topological insulator nanoribbons.
AB  - A topological insulator is the state of quantum matter possessing gapless spin
      locking surface states across the bulk band gap, which has created new
      opportunities from novel electronics to energy conversion. However, the large
      concentration of bulk residual carriers has been a major challenge for revealing
      the property of the topological surface state by electron transport measurements.
      Here we report the surface-state-dominant transport in antimony-doped, zinc oxide
      encapsulated Bi(2)Se(3) nanoribbons with suppressed bulk electron concentration.
      In the nanoribbon with sub-10-nm thickness protected by a zinc oxide layer, we
      position the Fermi levels of the top and bottom surfaces near the Dirac point by
      electrostatic gating, achieving extremely low two-dimensional carrier
      concentration of 2*10(11) cm(-2). The zinc oxide-capped, antimony-doped
      Bi(2)Se(3) nanostructures provide an attractive materials platform to study
      fundamental physics in topological insulators, as well as future applications.

PMID- 22453831
TI  - FAD-dependent lysine-specific demethylase-1 regulates cellular energy
      expenditure.
AB  - Environmental factors such as nutritional state may act on the epigenome that
      consequently contributes to the metabolic adaptation of cells and the organisms.
      The lysine-specific demethylase-1 (LSD1) is a unique nuclear protein that
      utilizes flavin adenosine dinucleotide (FAD) as a cofactor. Here we show that
      LSD1 epigenetically regulates energy-expenditure genes in adipocytes depending on
      the cellular FAD availability. We find that the loss of LSD1 function, either by
      short interfering RNA or by selective inhibitors in adipocytes, induces a number
      of regulators of energy expenditure and mitochondrial metabolism such as
      PPARgamma coactivator-1alpha resulting in the activation of mitochondrial
      respiration. In the adipose tissues from mice on a high-fat diet, expression of
      LSD1-target genes is reduced, compared with that in tissues from mice on a normal
      diet, which can be reverted by suppressing LSD1 function. Our data suggest a
      novel mechanism where LSD1 regulates cellular energy balance through coupling
      with cellular FAD biosynthesis.

PMID- 22453832
TI  - Neural circuits in the brain that are activated when mitigating criminal
      sentences.
AB  - In sentencing guilty defendants, jurors and judges weigh 'mitigating
      circumstances', which create sympathy for a defendant. Here we use functional
      magnetic resonance imaging to measure neural activity in ordinary citizens who
      are potential jurors, as they decide on mitigation of punishment for murder. We
      found that sympathy activated regions associated with mentalising and moral
      conflict (dorsomedial prefrontal cortex, precuneus and temporo-parietal
      junction). Sentencing also activated precuneus and anterior cingulate cortex,
      suggesting that mitigation is based on negative affective responses to murder,
      sympathy for mitigating circumstances and cognitive control to choose numerical
      punishments. Individual differences on the inclination to mitigate, the sentence
      reduction per unit of judged sympathy, correlated with activity in the right
      middle insula, an area known to represent interoception of visceral states. These
      results could help the legal system understand how potential jurors actually
      decide, and contribute to growing knowledge about whether emotion and cognition
      are integrated sensibly in difficult judgments.

PMID- 22453833
TI  - Poly(ADP-ribose) controls DE-cadherin-dependent stem cell maintenance and oocyte
      localization.
AB  - Within the short span of the cell cycle, poly(ADP-ribose) (pADPr) can be rapidly
      produced by poly(ADP-ribose) polymerases and degraded by poly(ADP-ribose)
      glycohydrolases. Here we show that changes in association between pADPr and
      heterogeneous nuclear ribonucleoproteins (hnRNPs) regulate germline stem cell
      (GSC) maintenance and egg chamber polarity during oogenesis in Drosophila. The
      association of pADPr and Hrp38, an orthologue of human hnRNPA1, disrupts the
      interaction of Hrp38 with the 5'-untranslated region of DE-cadherin messenger
      RNA, thereby diminishing DE-cadherin translation in progenitor cells. Following
      the reduction of DE-cadherin level, GSCs leave the stem cell niche and
      differentiate. Defects in either pADPr catabolism or Hrp38 function cause a
      decrease in DE-cadherin translation, leading to a loss of GSCs and
      mislocalization of oocytes in the ovary. Taken together, our findings suggest
      that Hrp38 and its association with pADPr control GSC self-renewal and oocyte
      localization by regulating DE-cadherin translation.

PMID- 22453834
TI  - Past daily light cycle recorded in the strontium/calcium ratios of giant clam
      shells.
AB  - The historical record of daily light cycle in tropical and subtropical regions is
      short. Moreover, it remains difficult to extract this cycle in the past from
      natural archives such as biogenic marine carbonates. Here we describe the precise
      analysis of Sr/Ca, Mg/Ca, and Ba/Ca ratios in a cultivated giant clam shell,
      using a laterally high-resolution secondary ion mass spectrometer with 2 MUm
      resolution. The Sr/Ca ratio exhibits striking diurnal variations, reflecting the
      daily light cycle. A clear seasonal variation in Sr/Ca is also observed in
      another longer set of measurements with 50 MUm resolution. Light-enhanced
      calcification and elemental transportation processes, in giant clam and symbiotic
      algae, may explain these diurnal and annual variations. This opens the
      possibility to develop the Sr/Ca ratio from a giant clam shell as an effective
      proxy for parameters of the daily light cycle.

PMID- 22453835
TI  - Quantum mechanics can reduce the complexity of classical models.
AB  - Mathematical models are an essential component of quantitative science. They
      generate predictions about the future, based on information available in the
      present. In the spirit of simpler is better; should two models make identical
      predictions, the one that requires less input is preferred. Yet, for almost all
      stochastic processes, even the provably optimal classical models waste
      information. The amount of input information they demand exceeds the amount of
      predictive information they output. Here we show how to systematically construct
      quantum models that break this classical bound, and that the system of minimal
      entropy that simulates such processes must necessarily feature quantum dynamics.
      This indicates that many observed phenomena could be significantly simpler than
      classically possible should quantum effects be involved.

PMID- 22453837
TI  - Metal-free TEMPO-catalyzed oxidative C-C bond formation from Csp3-H bonds using
      molecular oxygen as the oxidant.
AB  - An efficient TEMPO-catalyzed oxidative C-C bond formation with two Csp(3)-H bonds
      using molecular oxygen as the oxidant has been developed. The novel
      transformation provides a new strategy for the TEMPO-O(2) catalysis to construct
      C-C bonds. The advantages of this method include: (1) relatively mild and neutral
      conditions; (2) simplicity and safety of operation; (3) a stoichiometric amount
      of dangerous oxidants, any transition metals, additives, even solvent, is not
      required.

PMID- 22453836
TI  - Graphene-based wireless bacteria detection on tooth enamel.
AB  - Direct interfacing of nanosensors onto biomaterials could impact health quality
      monitoring and adaptive threat detection. Graphene is capable of highly sensitive
      analyte detection due to its nanoscale nature. Here we show that graphene can be
      printed onto water-soluble silk. This in turn permits intimate biotransfer of
      graphene nanosensors onto biomaterials, including tooth enamel. The result is a
      fully biointerfaced sensing platform, which can be tuned to detect target
      analytes. For example, via self-assembly of antimicrobial peptides onto graphene,
      we show bioselective detection of bacteria at single-cell levels. Incorporation
      of a resonant coil eliminates the need for onboard power and external
      connections. Combining these elements yields two-tiered interfacing of peptide
      graphene nanosensors with biomaterials. In particular, we demonstrate integration
      onto a tooth for remote monitoring of respiration and bacteria detection in
      saliva. Overall, this strategy of interfacing graphene nanosensors with
      biomaterials represents a versatile approach for ubiquitous detection of
      biochemical targets.

PMID- 22453838
TI  - Closure of interatrial defects by immediate-release patch.
AB  - The Immediate-Release Patch is the newest version of the Transcatheter Patch,
      which is a bioabsorbable device for the closure of cardiac defects. Closure of 12
      atrial septal defects and 1 fenestration was attempted using this device. Of the
      13 devices used, 12 were implanted successfully (including that for the
      fenestration), whereas 1 device moved from the original position and was
      retrieved percutaneously. No other major adverse events occurred. After a median
      follow-up period of 11 months, trivial (<= 2-mm) residual shunts remained in two
      patients, and a significant residual defect (7 mm) remained in 1 patient. The
      major advantages of this device include its wirelessness, its bioabsorbablity,
      potential application for defects up to 30 mm using only three sizes, its easier
      retrieval, and its ability to occlude defects with a deficient rim and some
      ostium primum and sinus venosus type defects. In contrast to the metal devices,
      it is bulkier and has a different application method requiring operator
      familiarity, and it sometimes leaves residual shunts.

PMID- 22453839
TI  - Secundum atrial septal defect with interrupted inferior vena cava and azygos
      continuation: transfemoral closure in a 3-year old boy.
AB  - A secundum atrial septal defect (ASD 2) was closed percutaneously via the
      transfemoral approach in a 3-year-old boy with interrupted inferior vena cava and
      azygos continuation. The procedure was guided by transesophageal echocardiography
      and fluoroscopy using conscious sedation. Successful transhepatic and jugular
      accesses in similar patients are described. This is the first pediatric report
      describing a transfemoral closure of a secundum atrial septum defect via azygos
      continuation.

PMID- 22453840
TI  - Pulmonary interstitial glycogenosis associated with pulmonary hypertension and
      hypertrophic cardiomyopathy.
AB  - A neonate with pulmonary interstitial glycogenosis, pulmonary hypertension, and
      hypertrophic cardiomyopathy is described. The fatal outcome for this patient
      contrasts with the reported favorable prognosis associated with isolated
      pulmonary interstitial glycogenosis. To the authors' knowledge, the association
      of pulmonary interstitial glycogenosis and hypertrophic cardiomyopathy has not
      been reported previously. The authors have broadened the phenotype of pulmonary
      interstitial glycogenosis and demonstrate the diagnostic value of lung biopsy in
      cases of unexplained neonatal pulmonary hypertension.

PMID- 22453841
TI  - Evaluation of N-acetylcysteine treatment in acute pancreatitis-induced lung
      injury.
AB  - OBJECTIVE: Pulmonary complications are frequent during acute pancreatitis (AP).
      We investigate the effects of N-acetylcysteine (NAC) on lung injury in mild and
      severe AP. ANIMALS AND TREATMENT: Mild and severe AP was induced in rats by bile
      pancreatic duct obstruction (BPDO) and infusion of 3.5 % sodium taurocholate
      (NaTc) into the bile-pancreatic duct, respectively. NAC (50 mg/kg) was given 1 h
      before and 1 h after AP. METHODS: Amylase activity was measured in plasma. Lungs
      were harvested for mRNA expression analysis of monocyte chemoattractant protein-1
      (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and
      intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity and
      histological examination. RESULTS: Hyperamylasemia was reduced by NAC in both AP
      models. NAC down-regulated MCP-1, CINC and P-selectin in BPDO- but not in NaTc
      induced AP. Pulmonary insults did not vary in mild AP and were exacerbated in
      severe AP by NAC treatment. NAC reduced lung MPO activity in mild but not in
      severe AP. CONCLUSIONS: Although NAC treatment down-regulated inflammatory
      mediators in lungs during AP it did not prevent leukocyte infiltration, which
      could be responsible for maintaining the lung injury. As a result, NAC aggravated
      the lung damage in severe AP and failed to exert beneficial effects in the mild
      disease model.

PMID- 22453842
TI  - Isothiocyanates inhibit psoriasis-related proinflammatory factors in human skin.
AB  - OBJECTIVE: 4-Methylthiobutylisothiocyanate (MTBI), the main rocket (Eruca sativa)
      seed isothiocyanate (ITC), and its oxidized form, sulforaphane (SFN), were
      assessed for their potential effects on psoriasis-related factors. METHODS: MTBI
      and SFN were evaluated for their effect on mRNA expression and cytokine secretion
      in vitro in human monocytes and macrophage-like cells and ex vivo in topically
      treated inflamed human skin. In addition, they were assayed in vivo for
      morphological changes in topically treated psoriasiform human skin in severe
      combined immunodeficient (SCID) mice. RESULTS: MTBI and SFN contributed to the
      prevention of inflammation development and reduced ongoing inflammation by
      downregulating lipopolysaccharide (LPS)-induced mRNA expression of the psoriasis
      related cytokines, interleukin (IL)-12/23p40 (25-58 %), tumor necrosis factor
      (TNF)-alpha (15-37 %) and IL-6 (25-71 %), in human macrophage-like cells. In
      monocytes, they tended to act additively on cytokine mRNA and reduced IL-12/23p40
      (51 %) secretion. In an ex-vivo inflamed human skin organ culture, MTBI (1
      MUg/ml) reduced the secretion of IL-1 (39 %) and IL-6 (32 %). Moreover, 2/8 and
      3/8 of the MTBI- and SFN-treated psoriasiform SCID mice, respectively, recovered
      partially or entirely from the psoriasiform process. CONCLUSIONS: Results from
      these models indicate the potential of rocket seed ITCs as biological agents in
      the therapy of psoriasis and inflammation-related skin diseases.

PMID- 22453843
TI  - Increased serum levels of soluble CD163 in patients with scleroderma.
AB  - CD163 is a 130-kDa, type I transmembrane protein belonging to group B of the
      cysteine-rich scavenger receptor family. Expression of CD163 is constitutive
      and/or induced by some stimuli on circulating monocytes and most tissue
      macrophages. An approximately 130-kDa soluble form of human CD163 is released
      from the cell surface by proteolysis after oxidative stress or inflammatory
      stimuli. Thus, an elevated level of circulating soluble CD163 (sCD163) has been
      reported in diabetes mellitus, which is one of the oxidative conditions. We have
      already acknowledged that scleroderma (SSc) is one of the oxidative conditions.
      Therefore, we conducted the measurement of serum sCD163 in SSc patients. After
      receiving the informed consents, 56 SSc patients were examined; 20
      dermatomyositis patients were used as disease controls and 40 persons were used
      as healthy controls. Blood samples were collected, and the concentration of serum
      sCD163 was measured by ELISA (human CD163, R&D Systems). Other parameters in the
      blood of SSc patients were also examined. Statistical analyses were performed
      using Mann-Whitney U test, and the relationship between parameters was
      statistically examined by Spearman's rank test. Serum sCD163 levels were elevated
      in SSc patients compared with normal controls (p < 0.01), with similar levels
      between limited SSc and diffuse SSc patients. SSc patients with pulmonary
      fibrosis had increased serum levels of sCD163 than those without pulmonary
      fibrosis (p < 0.05). SSc patients with elevated sCD163 levels had increased serum
      levels of IgG than those with normal sCD163 levels (p < 0.05). Serum sCD163
      levels correlated positively with pulsatility index in SSc patients (p = 0.0009,
      r = 0.534). These results suggest that oxidative stress may play an important
      role in immunological abnormalities, renal circulation, and pulmonary fibrosis of
      SSc.

PMID- 22453845
TI  - We are just getting started.

PMID- 22453844
TI  - Deep water running and general practice in primary care for non-specific low back
      pain versus general practice alone: randomized controlled trial.
AB  - There is equivocal evidence regarding the benefits of aquatic aerobic exercise
      for non-specific chronic low back pain (NSCLBP) in addition to standard care in
      general practice consisting of education and advice. The purpose of this study
      was to compare the addition of deep water running (DWR) to standard general
      practice (GP) on NSCLBP versus GP care alone on pain, physical and mental health
      and disability. In this single-blind randomised controlled trial, 58 subjects
      with NSCLBP were recruited from primary care. The control group received GP care
      consisting of a physician's consultation and educational booklet only. The
      experimental group received additional 30-min sessions of DWR three times a week
      for 15 weeks at the individualized aerobic threshold. Measurements were made pre-
      and post-intervention and at 1-year follow-up. Both groups showed improvement.
      The difference between treatment effects at longest follow-up of 1 year was -26.0
      (-40.9 to -11.1) mm on the VAS (p < 0.05), -2.5 (-5.7 to -0.2) points in RMQ for
      disability (p < 0.05), 3.3 (10.0 to 24.7) points on physical health in the
      physical summary component of the Spanish Short Form 12 (SF-12; p < 0.05) and 5.8
      (8.6 to 34.7) points on the mental summary component of the SF-12 (p < 0.05), in
      favour of the DWR group. For patients with NSCLBP, the addition of DWR to GP was
      more effective in reducing pain and disability than standard GP alone, suggesting
      the effectiveness and acceptability of this approach with this group of patients.

PMID- 22453846
TI  - SGS Research Handbook-2nd Edition.

PMID- 22453847
TI  - Vaginal paravaginal repair with porcine small intestine submucosa: midterm
      outcomes.
AB  - OBJECTIVE: : This study aimed to determine the midterm efficacy of porcine small
      intestine submucosa for paravaginal repairs of anterior vaginal prolapse.
      METHODS: : One hundred five women underwent repairs between 2003 and 2006 and met
      our inclusion criteria. Women were invited to return for a pelvic examination and
      to fill out validated questionnaires. Objective failure was defined as anterior
      prolapse recurrence at or beyond the hymen. RESULTS: : Fifty-nine women (56%)
      were available for follow-up. Median age of patients was 60 years (range, 26-80
      years) and 83% had a parity of 2 or more. Ninety-seven percent of patients had a
      preoperative prolapse stage of 2 or more. Follow-up ranged from 1 to 5 years
      (median, 27.5 months; interquartile range, 14.5). The most common postoperative
      complication was transient voiding dysfunction (23.7%). Objective cure rate was
      68.8%. A positive change in bladder, vaginal, and bowel symptoms (a little
      better, much better, or very much better) was reported by 69.5%, 59.3%, and 25.5%
      of women, respectively. Thirty-one women (52.5%) were sexually active at
      postoperative follow-up. Only 4 women (6.8%) were not sexually active because of
      pelvic symptoms. Dyspareunia was reported by 8.3% of the 48 women who returned
      for a clinic follow-up. Twenty-four women (40.7%) were not sexually active
      postoperatively, for reasons unrelated to their surgeries. CONCLUSIONS: : Vaginal
      paravaginal repair using porcine xenograft is a safe procedure whose long-term
      efficacy needs further evaluation through prospective trials.

PMID- 22453848
TI  - Structure and innervation of the labia minora: more than minor skin folds.
AB  - OBJECTIVE: : The objective of this study was to examine the histologic features
      of the labia minora, within the context of the female sexual response. METHODS: :
      Eight cadaver vulvectomy specimens were used for this study. All specimens were
      embedded in paraffin and were serially sectioned. Selected sections were stained
      with hematoxylin and eosin, elastic Masson trichrome, and S-100 antibody stains.
      RESULTS: : The labia minora are thinly keratinized structures. The primary
      supporting tissue is collagen, with many vascular and neural elements structures
      throughout its core and elastin interspersed throughout. CONCLUSIONS: : The labia
      minora are specialized, highly vascular folds of tissue with an abundance of
      neural elements. These features corroborate previous functional and observational
      data that the labia minora engorge with arousal and have a role in the female
      sexual response.

PMID- 22453849
TI  - Patient preferences for different severities of and treatments for overactive
      bladder.
AB  - OBJECTIVE: : Symptoms of overactive bladder (OAB) can have profound effects on
      women's quality of life. However, quantitative data on how women value these
      symptoms and their treatments are limited. We sought to assess women's
      preferences, which are referred to as utilities, for different severities of and
      treatment options for OAB. METHODS: : Eighty women-40 with OAB symptoms and 40
      without OAB-were recruited from urogynecology and urology practices at an
      academic institution from April to November 2009. A single, trained interviewer
      administered a computerized preference elicitation tool to measure preferences
      for 4 OAB severity levels (urgency/frequency and mild, moderate, and severe urge
      incontinence), as well as 3 OAB treatments with and without adverse effects or
      complications, which included (1) anticholinergic medications, (2) botulinum
      toxin injection, and (3) sacral neuromodulation. Preferences were assessed using
      the time trade-off (TTO) method. RESULTS: : Median TTO scores for OAB decreased
      as severity increased (urgency/frequency, 0.88; mild, 0.92; moderate, 0.85;
      severe, 0.73). Median TTO scores assigned to anticholinergic medications were
      higher (0.93) than those for botulinum (0.88) and sacral neuromodulation (0.85),
      and adverse effects or complications lowered the utilities for each treatment
      (anticholinergics, 0.88; botulinum, 0.75; and sacral neuromodulation, 0.78).
      CONCLUSIONS: : Women view symptoms of OAB, particularly moderate or severe
      symptoms, as being quite burdensome. The degree of invasiveness and the number of
      adverse effect/complications are important contributors to the utilities that
      women assign to the various treatment options.

PMID- 22453850
TI  - Knowledge and perceptions of pelvic floor disorders among african american and
      latina women.
AB  - OBJECTIVE: : The objective of this study was to explore knowledge, barriers to
      seeking sociocultural perceptions of pelvic floor disorders (PFDs) among African
      American (AA) and Latina (LA) community-dwelling women. METHODS: : Thirty-two
      women participated in 4 focus groups. The sample included AA and LA women aged 24
      to 77 years. Focus groups were stratified by age and race/ethnicity. Discussion
      questions included knowledge of and related health needs and barriers to seeking
      care with respect to PFDs, urinary incontinence, and pelvic organ prolapse.
      Demographics and basic knowledge and experience with PFDs were also captured by
      survey. RESULTS: : Several significant themes emerged from the data. AA and LA
      women had general misconceptions about PFDs and were unaware of PFDs causes,
      symptoms, and available treatments. Women were eager to receive more information,
      particularly prevention information that could be shared with their daughters. A
      major barrier to seeking care was the pattern of placing family demands before
      their own health needs. CONCLUSIONS: : Findings suggest that there is a gap in
      information on PFDs among AA and LA women, yet a demand for information exists.
      Sociocultural perspectives discerned from focus group with AA and LA women can be
      used to tailor educational information and materials on PFDs. Findings may
      increase health provider awareness of the unique sociocultural barriers to
      seeking care for AA and LA women and improve patient education on PFDs.

PMID- 22453851
TI  - Transvaginal repair and graft interposition for rectovaginal fistula due to a
      neglected pessary: case report and review of the literature.
AB  - BACKGROUND: : There are few reported cases of rectovaginal fistula due to a
      neglected pessary, with few data to guide management. CASE: : An 83-year-old lady
      presented with an impacted Gellhorn pessary 5 years after insertion. Upon removal
      of the pessary in the operating room, a 4-cm high rectovaginal fistula was
      discovered. An immediate transvaginal layered repair was performed with porcine
      dermal graft interposition and partial obliteration of the posterior vagina. At 8
      months' follow-up, the patient remained asymptomatic with normal bowel function.
      CONCLUSION: : A large, high rectovaginal fistula due to a neglected pessary can
      be repaired vaginally with the use of a graft and partial obliteration of the
      posterior vagina to provide additional layers of closure, without the need for
      colostomy. The literature is reviewed, focusing on the management of pessary
      related rectovaginal fistula and the role of graft augmentation.

PMID- 22453852
TI  - Transobturator tape removal: a cautionary tale.

PMID- 22453853
TI  - InterStim Sacral Neuromodulation and Botox Botulinum-A Toxin Intradetrusor
      Injections for Refractory Urge Urinary Incontinence: A Decision Analysis
      Comparing Outcomes Including Efficacy and Complications.
AB  - OBJECTIVE: : Overactive bladder is a common disease for which current
      pharmaceutical therapy is often unsatisfactory. Newer modalities, including Botox
      and InterStim, can be used when antimuscarinics fail. We compare InterStim and
      Botox using decision analysis. METHODS: : A Markov state transition decision
      analysis model was constructed using values for efficacy and complications from
      the literature. Overall utility was compared monthly. Multiple 1-way sensitivity
      analyses were performed. RESULTS: : For every month during the simulation,
      overall utility was higher for Botox than InterStim. After 54 months, cumulative
      utility was 3.86 versus 3.74, favoring Botox for an average yearly quality
      adjusted life-year value of 0.86 versus 0.83. All differences were less than
      minimally important differences for utilities. Few meaningful thresholds were
      established supporting the robustness of the model. CONCLUSIONS: : Until
      appropriately powered randomized controlled trials are available, both InterStim
      and Botox are reasonable and effective strategies with similar outcomes.

PMID- 22453854
TI  - Shifts in national rates of inpatient prolapse surgery emphasize current coding
      inadequacies.
AB  - OBJECTIVE: : This study aimed to assess national rates, types, and routes of
      inpatient surgery for pelvic organ prolapse in the United States in 1998 compared
      to those in 2007. METHODS: : We used the 1998 and 2007 Nationwide Inpatient
      Sample, which represents a stratified, random sample of discharge data from US
      hospitals. We included women 20 years and older who underwent surgery for
      prolapse based on diagnosis and procedure codes of the International
      Classification of Disease, 9th Revision, Clinical Modification. We calculated the
      number of women undergoing surgery each year and incidence rates. RESULTS: : The
      total number of women undergoing prolapse surgeries was 92,503 in 1998 versus
      113,646 in 2007. The incidence rate of surgery increased slightly, from 90.8 to
      100.9 per 100,000 women, respectively. The most common procedure was
      hysterectomy, representing approximately half of prolapse surgeries in 1998 and
      2007. Suspension procedures accounted for 18.8% of procedures in 2007, an
      increase from 6.1% in 1998. Surgeries performed via a minimally invasive route
      increased from 4.8% in 1998 to 9.4% in 2007. However, it was difficult to
      determine the route for many procedures based on current ICD-9 codes. There were
      also no codes that specifically designated mesh kit procedures or minimally
      invasive sacrocolpopexies. CONCLUSIONS: : During the last decade, the rate of
      inpatient prolapse surgery has slightly increased. The proportion of suspension
      procedures has increased; however, it is difficult to determine the route of
      these procedures based on current ICD-9 codes. These findings emphasize that ICD
      9 procedure codes have not kept up with changes in clinical practice.

PMID- 22453856
TI  - Effects of swim stress and fluoxetine on 5-HT1A receptor gene expression and
      monoamine metabolism in the rat brain regions.
AB  - Changes in gene expression of the brain serotonin (5-HT) 1A receptors may be
      important for the development and ameliorating depression, however identification
      of specific stimuli that activate or reduce the receptor transcriptional activity
      is far from complete. In the present study, the forced swim test (FST) exposure,
      the first stress session of which is already sufficient to induce behavioral
      despair in rats, significantly increased 5-HT1A receptor mRNA levels in the
      brainstem, frontal cortex, and hippocampus at 24 h. In the brainstem and frontal
      cortex, the elevation in the receptor gene expression after the second forced
      swim session was not affected following chronic administration of fluoxetine,
      while in the cortex, both control and FST values were significantly reduced in
      fluoxetine-treated rats. In contrast to untreated rats, no increase in
      hippocampal 5-HT1A receptor mRNA was observed in response to FST in rats
      chronically treated with fluoxetine. Metabolism of 5-HT (5-HIAA/5-HT) in the
      brainstem was significantly decreased by fluoxetine and further reduced by swim
      stress, showing a certain degree of independence of these changes on 5-HT1A
      receptor gene expression that was increased in this brain region only after the
      FST, but not after fluoxetine. FST exposure also decreased the brainstem dopamine
      metabolism, which was unexpectedly positively correlated with 5-HT1A receptor
      mRNA levels in the frontal cortex. Together, these data suggest that the effects
      of the forced swim stress as well as fluoxetine involve brain region-dependent
      alterations in 5-HT1A receptor gene transcription, some of which may be
      interrelated with concomitant changes in catecholamine metabolism.

PMID- 22453857
TI  - Clinical indications for musculoskeletal ultrasound: a Delphi-based consensus
      paper of the European Society of Musculoskeletal Radiology.
AB  - OBJECTIVE: To develop clinical guidelines for musculoskeletal ultrasound (MSKUS)
      referral in Europe. METHODS: Sixteen musculoskeletal radiologists from seven
      European countries participated in a consensus-based interactive process (Delphi
      method) using consecutive questionnaires and consensus procedure meetings at
      several European radiology meetings. The evaluation of musculoskeletal diseases
      was established by literature reviews, followed by consensus on clinical utility
      in three consensus meetings. This involved a thorough, transparent, iterative
      approach which including interview, questionnaire, Delphi and standard setting
      methodologies. European MSK radiologists with a special interest in MSKUS formed
      two different expert groups who worked on reaching a consensus in the first two
      meetings. The third meeting resolved questions that did not achieve a consensus
      level of 67% using the first two questionnaires. RESULTS: On expert consensus,
      the use of MSKUS is indicated to detect joint synovitis, fluid and septic
      effusion for potential aspiration, and poorly indicated to detect loose bodies.
      Recommendations for most appropriate use of musculoskeletal ultrasound are
      reported in six areas relevant to musculoskeletal ultrasound: hand/wrist, elbow,
      shoulder, hip, knee and ankle/foot. CONCLUSION: A comprehensive evidence-based,
      expert consensus-defined educational framework on clinical ultrsound is
      presented. This should facilitate referrals for this important imaging technique
      throughout Europe. KEY POINTS: Musculoskeletal ultrasound is indicated for
      detecting joint synovitis, effusions and fluid collections. * Musculoskeletal
      ultrasound is poor at detecting loose bodies. * Musculoskeletal ultrasound is
      relevant for most joints.

PMID- 22453858
TI  - The clinical value of MRA at 3.0 T for the diagnosis and therapeutic planning of
      patients with subarachnoid haemorrhage.
AB  - OBJECTIVE: To evaluate the clinical value of unenhanced magnetic resonance
      angiography (MRA) at 3.0 T for the diagnosis and therapeutic planning of patients
      with subarachnoid haemorrhage (SAH). METHODS: A total of 165 patients with SAH
      were referred for three-dimensional time-of-flight MRA (3D-TOF-MRA) before
      digital subtraction angiography (DSA). For each aneurysm, 3D-TOF-MRA was used to
      determine whether the aneurysm was suitable for coil placement with or without
      balloon/stent-assisted coiling, surgical clipping or conservative treatment.
      Treatment planning with 3D-TOF-MRA was compared with actual treatment decisions
      or treatment that had been carried out in each aneurysm decided using DSA.
      RESULTS: The aneurysm-based evaluation yielded accuracy of 96.9%, sensitivity of
      97.6%, specificity of 93.1%, positive predictive value (PPV) of 98.8% and
      negative predictive value (NPV) of 87.1%, in the detection of intracranial
      aneurysms. Treatment planning could be correctly made on the basis of aneurysm
      anatomy and working view by volume rendering (VR) 3D-TOF-MRA with accuracy,
      sensitivity, specificity, PPV and NPV of 94.9%, 94.0%, 100%, 100% and 74.4%,
      respectively, on a per aneurysm-based evaluation. CONCLUSIONS: VR 3D-TOF-MRA
      offers high diagnostic accuracy in the detection of ruptured intracranial
      aneurysms, and appears to be an effective treatment planning tool for most
      patients with SAH. KEY POINTS: VR 3D-TOF-MRA offers high diagnostic accuracy for
      detecting ruptured intracranial aneurysms. * VR 3D-TOF-MRA helps treatment
      planning for patients with subarachnoid haemorrhage. * 3D-TOF-MRA is non-invasive
      and avoids using ionising radiation or contrast agents.

PMID- 22453859
TI  - Standard 1.5-T MRI of endometrial carcinomas: modest agreement between
      radiologists.
AB  - OBJECTIVES: To evaluate pelvic magnetic resonance imaging (MRI) interobserver
      agreement for the detection of deep myometrial invasion, cervical stroma invasion
      and lymph node metastases in endometrial carcinoma patients in relation to
      surgical staging. METHODS: Fifty-seven patients with histologically confirmed
      endometrial carcinoma were prospectively included in a study of preoperative 1.5
      T MRI. Four radiologists, blinded to patient data, independently reviewed the
      images for the presence of deep myometrial invasion, cervical stroma invasion and
      lymph node metastases. Kappa coefficients for interobserver agreement and
      diagnostic performances for each observer were calculated using final surgical
      staging results (FIGO 09) as reference standard. RESULTS: Overall agreement among
      all observers was moderate for cervical stroma invasion (kappa = 0.50 [95% CI
      0.27-0.73]) and lymph node metastases (kappa = 0.56 [0.09-0.80]) and fair for
      deep myometrial invasion (kappa = 0.39 [0.26-0.55]). Sensitivity (specificity)
      values for the four observers were 72-92% (44-63%) for deep myometrial invasion,
      38-63% (82-94%) for cervical stroma invasion and 25-38% (90-100%) for lymph node
      metastases. CONCLUSIONS: Conventional MRI showed only modest interobserver
      agreement and diagnostic accuracy for detection of deep myometrial invasion,
      cervical stroma invasion and lymph node metastases. Improved methods are needed
      for preoperative imaging in the staging of endometrial carcinomas. KEY POINTS:
      MRI is an important tool for preoperative endometrial cancer staging. * Staging
      agreement based on pelvic MRI was modest among different observers. *
      Preoperative MRI alone was suboptimal in identifying high-risk patients. *
      Improved imaging and biomarkers may refine preoperative risk stratification in
      endometrial cancer.

PMID- 22453861
TI  - Phylogeny and evolution of Newcastle disease virus genotypes isolated in Asia
      during 2008-2011.
AB  - The full-length fusion (F) genes of 51 Newcastle disease (ND) strains isolated
      from chickens in Asia during the period 2008-2011 were genetically analyzed.
      Phylogenetic analysis showed that genotype VII of NDV still predominant in the
      domestic poultry of Asia. The sub-genotype VIIb circulated in the Iran and Indian
      sub-continent countries, whereas VIId sub-genotype existed in Far East countries.
      The non-synonymous to synonymous substitutions ratio was calculated 0.27 for VIId
      sub-genotype and 0.51 for VIIb sub-genotype indicates purifying/stabilizing
      selection which resulted in a low evolution rate in F gene of VIIb sub-genotype.
      There is evidence of localized positive selection when comparing these sub
      genotypes protein sequences. Five codons in F gene of ND viruses had a posterior
      probability >90% using the Bayesian method, indicating these sites were under
      positive selection. To identify sites under positive selection; amino acid
      substitution classified depends on their radicalism and neutrality. The results
      indicate that although most positions were under purifying selection and can be
      eliminated, a few positions located in sub-genotype specific regions were subject
      to positive selection.

PMID- 22453860
TI  - Genetic evolution of the H9N2 avian influenza virus in Korean poultry farms.
AB  - We performed whole genome sequencing of 22 H9N2 avian influenza viruses (AIV)
      isolated from domestic laying hens on farms between 2005 and 2008, and compared
      the sequences with viruses previously reported in Asia. A previous study revealed
      that two antigenically distinct sublineages were established within the MS96
      lineage by antigenic drift since the first H9N2 AIV outbreak in South Korea. We
      designated them as the 01310-like lineage and the 116/04-like lineage. Since late
      2004, most identified isolates in Korea have belonged to the 116/04-like lineage,
      however, in this study we found that six among twenty-two isolates were belonged
      to 01310-like lineage, indicating that the genetic divergence is still occurring
      after 2004. Furthermore, it is noteworthy that five isolates among the defined
      01310-like lineage had a 24 amino acid deletion in the neuraminidase stalk
      region, which were not in any other H9N2 isolates previously reported. The
      internal genes analysis demonstrated extensive reassortment events among isolates
      from poultry farms, live bird markets, and wild birds, and multiple new genotypes
      were identified. We identified several features of gene evolution in H9N2 AIV
      suggesting that the long-term H9N2 AIV surveillance study should be continued in
      South Korea.

PMID- 22453862
TI  - Validity of a brief measure of parental affective attitudes in high-risk
      preschoolers.
AB  - The current study investigated psychometric properties of the Family Affective
      Attitude Rating Scale (FAARS) for assessing parents' thoughts and feelings about
      their child, coded from a 5-min speech sample. Parental affective attitudes
      derive from previous experiences of parenting and child behavior, representations
      of the parent-child relationship and broader parental characteristics. Data were
      collected from mother-child dyads at ages 2 and 3 (N = 731; 49 % female) from a
      multi-ethnic and high-risk community sample. Multi-informant observations of
      parenting and questionnaire measures were used to test construct and discriminant
      validity. FAARS showed good internal consistency and high inter-rater agreement.
      Affective attitudes were related to mothers' perceptions of their daily hassles,
      their reports of conflict with their child, and observed measures of positive and
      harsh parenting. Negative affective attitudes uniquely predicted later child
      problem behavior, over and above maternal reports of and observed measures of
      parenting. Overall, results support the validity of FAARS coding in mothers of
      preschoolers, a previously untested group. FAARS is a novel measure, directly
      assessing maternal perceptions of the parent-child relationship, and indirectly
      providing an index of maternal affect, stress, and depressive symptoms. Its
      brevity and cost-effectiveness further enhance the potential use of the FAARS
      measure for clinical and research settings.

PMID- 22453865
TI  - Social cognition and visual perception in schizophrenia inpatients treated with
      first-and second-generation antipsychotic drugs.
AB  - PURPOSE: Social cognition captures affect recognition, social cue perception,
      "theory of mind," empathy, and attributional style. The aim of our study was to
      assess social cognition in schizophrenia inpatients being treated with first
      generation antipsychotic drugs (FGAs), n=28 (perphenazine and haloperidol, FGAs)
      or with second-generation antipsychotic drugs (SGAs), n=56 (olanzapine and
      clozapine, SGAs). SUBJECTS AND METHODS: Eighty-four patients completed the Facial
      Expression Recognition Test, the Voice Emotion Recognition Test, the Short
      Recognition Memory Test for Faces, and the Reading the Mind in the Eyes Test.
      Patients also completed the Visual Object and Space Perception Test (VOSP) as a
      control task, which would not engage social cognition. The patients were compared
      with fifty healthy controls matched for age and gender. RESULTS: There were no
      significant differences on social cognitive performance between the FGA- and SGA
      treatment groups. Nor was olanzapine superior to clozapine, FGAs or both.
      However, patients treated with FGAs performed significantly worse on VOSP
      compared to both groups treated with SGAs, a 10% difference. CONCLUSIONS: We
      cannot conclude that SGAs were associated with better social cognition than FGAs.
      However, there were small but significant advantages for SGAs in non-social
      visual processing function, as evaluated with the VOSP.

PMID- 22453866
TI  - Vaptans: a potential new approach for treating chronic hyponatremia in psychotic
      patients.
AB  - OBJECTIVE: Hyponatremia (serum sodium concentration [Na+] <136 mEq/L) is a
      potentially life-threatening condition often found chronically in patients with
      psychotic disorders. Vasopressin antagonists have recently been shown in short
      term studies to correct hyponatremia in diverse patient populations, including
      individuals with both psychosis and idiopathic hyponatremia. However, the safety
      and efficacy of long-term administration of vaptans is only beginning to be
      investigated. The objective of this study was to assess whether one of the
      vaptans, specifically tolvaptan, maintained its safety and efficacy over a
      prolonged period in patients with psychosis and chronic idiopathic hyponatremia.
      METHODS: SALTWATER was a multicenter, open-label extension of the Study of
      Ascending Levels of Tolvaptan in Hyponatremia. Of the 111 patients enrolled in
      SALTWATER, eight were patients with both psychosis and idiopathic hyponatremia.
      These eight subjects provided a total of 7,406 patient days of exposure to oral
      tolvaptan. RESULTS: Mean serum [Na+] in the eight psychotic patients increased
      from 131.6 mEq/L at baseline to >135 mEq/L throughout the observation period
      (p<0.05 versus baseline at most points). No drug-related adverse events led to
      study discontinuation. CONCLUSIONS: Chronic hyponatremia is known to have
      deleterious effects on the quality of life for many patient groups. These
      preliminary results suggest that oral tolvaptan provides rapid, effective, and
      safe treatment of chronic hyponatremia in patients with psychotic disorders and
      that the effect is safely sustained over long periods of time. These findings
      represent an important step forward in treating a significant unmet need in
      psychotic populations.

PMID- 22453863
TI  - Callous-unemotional traits as unique prospective risk factors for substance use
      in early adolescent boys and girls.
AB  - Youth with elevated conduct disorder (CD) symptoms who also have callous
      unemotional (CU) traits exhibit more antisocial behavior than youth without CU
      traits. However, evidence regarding whether CU traits increase risk of substance
      use over and above CD symptoms, and whether these associations differ for boys
      and girls, is scarce. Using the Developmental Pathways Project sample of 521
      middle school students, we examined whether adolescent- and parent-reported CU
      traits measured in 6th grade prospectively predicted the onset and recurrence of
      substance use and use-related impairment by 9th grade. We also examined the
      degree to which CU traits uniquely predicted substance use and impairment over
      and above CD symptoms, as well as whether gender moderated these associations.
      Results indicated that adolescent-reported CU traits increased the likelihood of
      substance use and impairment onset and recurrence by 9th grade. Analyses revealed
      that CD symptoms accounted for prospective associations between adolescent
      reported CU and substance use, but gender moderated these associations. Boys with
      elevated CU traits and CD symptoms were not more likely to report alcohol use
      onset or recurrence, but they were at highest risk of recurrent marijuana use,
      use of both alcohol and marijuana, and use-related impairment by 9th grade. Girls
      with low CU traits and high CD symptoms were most likely to report onset and
      recurrent use of alcohol, as well as recurrent marijuana use, use of both
      substances and impairment. Study findings highlight the importance of accounting
      for CD symptoms and gender when examining links between CU traits and substance
      use in early adolescence.

PMID- 22453867
TI  - Maternal schizophrenia: psychosocial treatment for mothers and their children.
AB  - OBJECTIVE: Psychosocial treatments that address the unique needs of mothers with
      schizophrenia and their children are sorely lacking. In striving to explore and
      understand treatment of maternal schizophrenia, this paper focuses on two
      objectives: 1) to identify and examine specialty psychosocial interventions for
      parents, notably mothers with schizophrenia and their offspring; and, 2) to
      describe recommendations for the development of specialty psychosocial treatment
      for this population. METHODS: A systematic literature search of peer-reviewed
      articles was conducted in PsycINFO, MEDLINE, CINAHL, Social Work Abstracts, and
      Social Service Abstracts databases prior to January 1, 2010. The authors reviewed
      each article for psychosocial interventions treating mothers diagnosed with
      schizophrenia and their children. Forty-three (n=43) studies were identified.
      RESULTS: Two areas of specialized psychosocial interventions designed to treat
      maternal schizophrenia and their children were identified: 1) inpatient
      interventions programs, primarily Mother Baby Units (MBU); and, 2) outpatient
      interventions programs. CONCLUSIONS: Interventions targeting mothers with
      schizophrenia spectrum illnesses and their children are lacking. Women with
      schizophrenia are at risk for not engaging in treatment due to fears of barriers
      and losing their children. Although scarce, inpatient MBUs offer focused
      treatment, but services are limited to the baby's first year. Minimal outpatient
      psychosocial treatments are available to this population. Flexible treatment
      approaches that incorporate environmental supports, childcare resources, child
      welfare systems, and family involvement are highly recommended.

PMID- 22453868
TI  - Iloperidone for the treatment of schizophrenia: an updated clinical review.
AB  - Iloperidone is a second-generation "atypical" antipsychotic whose primary
      mechanism of action is within the subclass of combined D2/5HT2A antagonism.
      Iloperidone was approved by the FDA in May 2009 for the treatment of
      schizophrenia. This review is a comprehensive synthesis of the history and
      clinical trials data leading up to approval, and evaluates iloperidone within the
      clinical context of how it compares with other available antipsychotics.

PMID- 22453869
TI  - A case of prolonged duration of untreated psychosis: barriers to treatment and
      strategies to improve the outcome.
AB  - Several factors may contribute to increase in duration of untreated psychosis
      (DUP). In most cases, early intervention, namely psychopharmacological or
      psychosocial intervention, is done after first-episode psychosis. It is important
      to know what factors can contribute to duration of untreated psychosis. During
      this phase, patients often display unspecific symptoms such as anxiety and
      depression, personality disorders, and abuse of alcohol or drugs. These symptoms
      could go unrecognized and, hence, cause a delay in seeking treatment. In
      addition, functional and social decline frequently occurs in the prodromal phase
      or in the early course of schizophrenia. The purpose of this paper is to
      highlight barriers that cause delay in treatment and to review early detection
      and specific treatment strategies that may help to improve outcomes leading to
      psychosocial recovery.

PMID- 22453870
TI  - A personal perspective:  100-year history of the humoral theory of
      transplantation.
AB  - The humoral theory states that antibodies cause the rejection of allografts. From
      1917 to 1929, extensive efforts were made to produce antibodies against tumors.
      It was finally realized that the antibodies were produced against the transplant
      antigens present on transplantable tumors, not against the tumor-specific
      antigens. To get around this problem, inbred mouse strains were developed,
      leading to identification of the transplant antigens determined by the H-2 locus
      of mice. The antibodies were hemagglutinating and cytotoxic antibodies. The
      analogous human leukocyte antigen system was established by analysis of
      lymphocytotoxic alloantibodies that were made by pregnant women, directed against
      mismatched antigens of the fetus. The human leukocyte antigen antibodies were
      then found to cause hyperacute rejection, acute rejection, and chronic rejection
      of kidneys. Antibodies appeared in almost all patients after rejection of
      kidneys. With Luminex single antigen bead technology, donor-specific antibodies
      could be identified before rise in serum creatinine and graft failure. Antibodies
      were shown to be predictive of subsequent graft failure in kidney, heart, and
      lung transplants: patients without antibodies had superior 4-year graft survival
      compared with those who did have antibodies. New evidence that antibodies are
      also associated with chronic failure has appeared for liver and islet
      transplants. Four studies have now shown that removal or reduction of antibodies
      result in higher graft survival. If removal of antibodies prevents chronic graft
      failure, final validation of the humoral theory can be achieved.

PMID- 22453871
TI  - Scanning laser pulses driven microfluidic peristaltic membrane pump.
AB  - We reported a pulsed laser driven peristaltic pump for driving fluid in
      multilayer polydimethylsiloxane (PDMS) microchannels. By synchronizing the
      dynamics of deforming membrane valves with pulsed laser generated bubbles, a
      maximum pumping rate of 460 pl s(-1) has been achieved.

PMID- 22453874
TI  - From fracture risk prediction to evaluating fracture patterns: recent advances in
      the epidemiology of osteoporosis.
AB  - Understanding the factors associated with fracture is one of the main research
      objective of the osteoporosis epidemiology field. Tools such as FRAX have overall
      improved the ability of clinicians and researchers to identify individuals at
      high risk of fragility fractures. However, the performance of these tools in
      specific subpopulations needs further examination. We highlight recent studies
      that have shown under- or overestimation of fractures using FRAX in
      subpopulations, as well as recently proposed modifications to this important
      algorithm. We also discuss recent evaluations of secular trends in fracture
      incidence.

PMID- 22453875
TI  - Macrocyclic depolymerization of arylene-ethynylene copolymers: a dynamic
      combinatorial method.
AB  - A dynamic combinatorial approach for the synthesis of arylene ethynylene
      macrocycles (AEMs) from linear polymers is described. By using readily available
      carbazolyl-ethynylene copolymers as starting materials we obtained a number of
      novel macrocycles that would be difficult to prepare by traditional methods.

PMID- 22453876
TI  - Brain abscesses in HIV-positive patients due to Pneumocystis jiroveci.
AB  - Cerebral toxoplasmosis is common in AIDS patients; however, pneumocystosis of the
      brain is rarely documented. We report a patient with AIDS hospitalized for brain
      abscesses. Stereotactic brain biopsy with immunofluorescence staining was
      positive for Pneumocystis jiroveci. The patient received high doses of
      cotrimoxazole and had a favorable clinical course.

PMID- 22453877
TI  - Age-at-onset in Huntington disease.
AB  - BACKGROUND: In Huntington disease, the accurate determination of age-at-onset is
      critical to identify modifiers and therapies that aim to delay it. METHODS:
      Retrospective data from the European Huntington's Disease Network's REGISTRY and
      PREDICT-HD, a longitudinal study in prodromal huntingtin gene expansion mutation
      carriers. Data (age, gender, CAG repeat length, parent affected, and Unified
      Huntington's Disease Rating Scale motor score, total functional capacity) from at
      least three visits in 423 REGISTRY and 124 PREDICT-HD participants were included.
      Data based extrapolations of individual age-at-onset using generalized linear
      mixed models based on individual slopes of motor score or total functional
      capacity, and predictions using the Langbehn, or Ranen formula, were compared
      with clinicians' estimates. RESULTS: Concordance was best for the observed age-at
      onset in PREDICT-HD and the calculated onset using the PREDICT-HD UHDRS
      longitudinal motor scores. This was superior to the REGISTRY data. For total
      functional capacity, the investigator's estimate was 4 years before the data
      derived age-at-onset. The concordance of predictions of probability of age-at
      onset is better with the observed age-at-onset in the PREDICT-HD data (difference
      in 25%tile -5 to 10 years) than the REGISTRY data (+/-20 years). CONCLUSIONS:
      Estimating or predicting age-at-onset in Huntington disease may be inaccurate. It
      can be useful to 1) add in the manifest population motor score regression derived
      age-at-onset as additional motor onset and 2) add total functional capacity
      regression derived age-at-onset for the onset of functional impact of Huntington
      disease when patients are in mid- to late-stage.

PMID- 22453878
TI  - Perhaps not such a great threat to public health in the UK.

PMID- 22453880
TI  - Proposed screening is too simple and not focused enough.

PMID- 22453881
TI  - Atrial fibrillation and rheumatoid arthritis are cardiovascular risk factors.

PMID- 22453882
TI  - No more fine needle aspiration biopsies?

PMID- 22453883
TI  - How good is the science?

PMID- 22453885
TI  - Access to specialist services is missing.

PMID- 22453886
TI  - Going to hell in a hand cart?

PMID- 22453888
TI  - Treat negative symptoms of schizophrenia early on.

PMID- 22453889
TI  - Is fluvoxamine a winner or a loser?

PMID- 22453890
TI  - Dementia is more frightening.

PMID- 22453891
TI  - Care of older people in hospitals is unacceptable, says think tank.

PMID- 22453892
TI  - Patient information leaflets about cancer trials are too complicated, finds
      study.

PMID- 22453893
TI  - Clinical testing and spinal cord removal in a mouse model for amyotrophic lateral
      sclerosis (ALS).
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      resulting in progressive degeneration of motoneurons. Peak of onset is around 60
      years for the sporadic disease and around 50 years for the familial disease. Due
      to its progressive course, 50% of the patients die within 30 months of symptom
      onset. In order to evaluate novel treatment options for this disease, genetic
      mouse models of ALS have been generated based on human familial mutations in the
      SOD gene, such as the SOD1 (G93A) mutation. Most important aspects that have to
      be evaluated in the model are overall survival, clinical course and motor
      function. Here, we demonstrate the clinical evaluation, show the conduction of
      two behavioural motor tests and provide quantitative scoring systems for all
      parameters. Because an in depth analysis of the ALS mouse model usually requires
      an immunohistochemical examination of the spinal cord, we demonstrate its
      preparation in detail applying the dorsal laminectomy method. Exemplary
      histological findings are demonstrated. The comprehensive application of the
      depicted examination methods in studies on the mouse model of ALS will enable the
      researcher to reliably test future therapeutic options which can provide a basis
      for later human clinical trials.

PMID- 22453894
TI  - Clinical and radiological outcomes of open versus minimally invasive
      transforaminal lumbar interbody fusion.
AB  - STUDY DESIGN: Prospective observational cohort study. OBJECTIVE: Comparison of
      clinical and radiological outcomes of single-level open versus minimally invasive
      (MIS) transforaminal lumbar interbody fusion (TLIF) at 6 months and 2-year follow
      up. There is recognition that more data are required to ascertain the benefits
      and risks of MIS vis-a-vis open TLIF. This study aims to report on one of the
      largest currently available series comparing the clinical and radiological
      outcomes of the two procedures with a minimum follow-up of 2 years. METHODS: From
      January 2002 to March 2008, 144 single-level open and MIS TLIF were performed at
      our centre, with 72 patients in each group. Clinical outcomes were based on
      patient-reported outcome measures recorded at the Orthopaedic Diagnostic Centre
      by independent assessors before surgery, at 6 months and 2 years post
      operatively. These were visual analogue scores (VAS) for back and leg pain,
      Oswestry disability index (ODI), short form-36 (SF-36), North American Spine
      Society (NASS) scores for neurogenic symptoms, returning to full function, and
      patient rating of the overall result of surgery. Radiological fusion based on the
      Bridwell grading system was also assessed at 6 months and 2 years post
      operatively by independent assessors. RESULTS: In terms of demographics, the two
      groups were similar in terms of patient sample size, age, gender, body mass index
      (BMI), spinal levels operated, and all the clinical outcome measures (p > 0.05).
      Perioperative analysis revealed that MIS cases have comparable operative duration
      (open: 181.8 min, MIS: 166.4 min, p > 0.05), longer fluoroscopic time (open: 17.6
      s, MIS: 49.0 s, p < 0.05), less intra-operative blood loss (open: 447.4 ml, MIS:
      50.6 ml, p < 0.05) and no post-operative drainage (open: 528.9 ml, MIS: 0 ml, p <
      0.05). MIS patients needed less morphine (open: 33.5 mg, MIS: 3.4 mg, p < 0.05)
      and were able to ambulate (open: 3.4 days, MIS: 1.2 days, p < 0.05) and be
      discharged from hospital earlier (open: 6.8 days, MIS: 3.2 days, p < 0.05). At 6
      months, clinical outcome analysis showed both groups improving significantly
      (>50.0%) and similarly in terms of VAS, ODI, SF-36, return to full function and
      patient rating (p > 0.05). Radiological analysis showed similar grade 1 fusion
      rates (open: 52.2%, MIS: 59.4%, p > 0.05) with small percentage of patients
      developing asymptomatic cage migration (open: 8.7%, MIS: 5.8%, p > 0.05). One
      major complication (open: myocardial infarction, MIS: screw malpositioning
      requiring subsequent revision) and two minor complications in each group (open:
      pneumonia and post-surgery anemia, MIS: incidental durotomy and pneumonia) were
      noted. At 2 years, continued improvements were observed in both groups as
      compared to the preoperative state (p > 0.05), with 50.8% of open and 58% of MIS
      TLIF patients returning to full function (p > 0.05). Almost all patients have
      Grade 1 fusion (open: 98.5 %, MIS: 97.0%, p > 0.05) with minimal new cage
      migration (open: 1.4 %, MIS: 0%, p > 0.05). CONCLUSIONS: MIS TLIF is a safe
      option for lumbar fusion, and when compared to open TLIF, has similar operative
      duration, good clinical and radiological outcomes, with additional significant
      benefits of less perioperative blood loss and pain, earlier rehabilitation, and a
      shorter hospitalization.

PMID- 22453895
TI  - The correlation between DTI parameters and levels of AQP-4 in the early phases of
      cerebral edema after hypoxic-ischemic/reperfusion injury in piglets.
AB  - BACKGROUND: Brain edema during the early stages of hypoxic-ischemic/reperfusion
      (HI/R) injury can be determined using diffusion tensor imaging (DTI). The change
      in ADC values has been correlated with the change in expression of AQP-4.
      OBJECTIVE: To determine cerebral edema at specific time intervals after HI/R
      injury using DTI modalities and discuss its relationship to the expression of
      aquaporin-4 (AQP-4). MATERIALS AND METHODS: Thirty newborn piglets were divided
      into six groups (2, 6, 12, 24, 48 and 72 h) after HI/R injury. The control group
      subjected to sham surgery included five piglets. DTI scans and
      immunohistochemistry of AQP-4 expression were performed on piglet brain. The
      relationship between DTI parameters (FA and ADC values) and the optical density
      (OD) of AQP-4 expression was determined. RESULTS: In the striatum, ADC values
      dropped and reached their lowest level at 24 h (F = 27.42, P < 0.05). In the
      subcortical border region, ADC values increased after a transient decrease and
      peaked at 48 h, demonstrating a significant difference from the control group (F
      = 50.25, P < 0.05). FA values in the internal capsules and subcortical white
      matter in HI/R models decreased continuously after HI/R, although no
      statistically significant difference from the control group was achieved. ADC and
      OD values of AQP-4 expression were positively correlated (r = 0.875, P < 0.05).
      CONCLUSIONS: The change in ADC value after HI/R injury correlates with the
      expression of AQP-4.

PMID- 22453896
TI  - The buncefield oil depot fire of 2005: potential air-pollution health impacts
      under alternative meteorological scenarios.
AB  - OBJECTIVE: To model the possible air pollution-related health impact of the 2005
      oil depot fire at Buncefield, near London, UK, under alternative meteorological
      conditions to those experienced at the time. DESIGN: Atmospheric dispersion
      modelling of the smoke plume was conducted under the range of meteorological
      conditions occurring throughout 2005 assuming constant particle emission rates.
      Population exposure to particle concentrations (PM10) was calculated by linking
      the atmospheric dispersion modelling data (2 km resolution) and postcode
      population data. Health impacts were estimated using time-series-based exposure
      response relationships for PM10 available from the epidemiological literature.
      MAIN OUTCOMES: Estimates of pollution-related deaths brought forward, emergency
      hospital admissions from respiratory problems and emergency hospital admissions
      from cardiovascular disease. FINDINGS: The highest four-day population exposure
      to PM10 for meteorological data from 2005 was predicted to occur between 5 and 8
      August 2005, when northerly winds would have carried the plume towards London and
      surrounding areas of high population density. On these days, we estimated the
      additional PM10 exposure would have resulted in around 12 extra deaths brought
      forward, and around 13 additional emergency hospital admissions and a similar
      additional number of emergency admissions for cardiovascular disease. These
      numbers are slightly greater than estimated deaths and emergency admissions
      attributable to regular anthropogenic PM10 concentrations in south east England
      over the same four day period. CONCLUSIONS: Although the particle pollution
      related health impacts of the Buncefield fire could have been higher under
      different meteorological conditions, it is unlikely that the impacts would be
      substantially greater than those attributable to regular anthropogenic particle
      pollution over the similar period. KEYWORDS: oil depot fire; health impact;
      epidemiology; air pollution; explosion; atmospheric dispersion modelling;
      exposure.

PMID- 22453897
TI  - Disasters at mass gatherings: lessons from history.
AB  - IntroductionReviews of mass gathering events have traditionally concentrated on
      crowd variables that affect the level and type of medical care needed. Crowd
      disasters at mass gathering events have not been fully researched and this review
      examines these aiming to provide future suggestions for event organisers, medical
      resource planners, and emergency services, including local hospital emergency
      departments.MethodsA review was conducted using computerised data bases: MEDLINE,
      The Cochrane Library, HMIC and EMBASE, with Google used to widen the search
      beyond peer-reviewed publications, to identify grey literature. All peer-review
      literature articles found containing information pertaining to lessons identified
      from mass gathering crowd disasters were analysed and reviewed. Disasters
      occurring in extreme weather events, and environmental leading to participant
      illness were not included. These articles were read, analysed, abstracted and
      summarised.Results156 articles from literature search were found detailing mass
      gathering disasters identified from 1971 - 2011. With only 21 cases found within
      peer-review literature. Twelve events were further documented as a case reports.
      Five events were examined as review articles while four events underwent
      commissioned inquiries. Analysis of cases were categorised in to crowd control,
      event access, fire safety, medical preparedness and emergency
      response.ConclusionsMass gathering events have an enormous potential to place a
      severe strain on the local health care system, and a mixture of high crowd
      density, restricted points of access, poor fire safety, minimum crowd control and
      lack of on-site medical care can lead to problems that end in
      disaster.KeywordsMass Gatherings, Mass Gathering Medicine, Disasters, Sporting
      Events, Olympic Games, Festivals, Concerts, Disaster, Stampede, Fire, Terrorism,
      Religious Event, Air ShowAbbreviationsDMAT - Public Health Service Disaster
      Medical Assistance Teams; EMS - Emergency Medical Services; NAEMSP - National
      Association of EMS Physicians;UNISDR - United Nations Strategy for Disaster
      Reduction.

PMID- 22453898
TI  - Huntington's like conditions in China, A review of published Chinese cases.
AB  - BACKGROUND: Knowledge about HD in China is lacking in the international
      literature. We have therefore analyzed the Chinese literature to thoroughly
      explore the clinical characteristics of Huntington disease in China. METHODS: A
      computer-based online search of China National Knowledge Infrastructure was
      performed to review case reports concerning HD published between January 1980 and
      April of 2011, and the clinical characteristics were extracted. RESULTS: A total
      of 92 studies involving 279 patients (157 males and 122 females) were collected,
      82.0% of which were from provinces of North China. Most of the cases (97.8%) had
      a family history of HD, and paternal inheritance (65.5%) was higher than maternal
      inheritance (34.5%). Onset age was 35.8 (+/- 11.8) years, death occurred with
      45.6 (+/- 13.5) years after a course of 11.6 (+/- 5.6) years. Involuntary
      movements were the most frequent reported presentation (found in 52.3%, including
      64.4% in the entire body, 19.8% in the upper limbs, and 13.7% in the head and
      face). Psychiatric symptoms at onset were reported in 16.1%, and cognitive
      impairment in 1.8%. With disease progression, 99.6% of patients had abnormal
      movements, 67.9% cognitive impairment, and 35.0% suffered psychiatric symptoms.
      Of the reported patients, only 22 underwent IT15 gene testing with positive
      results. CONCLUSION: HD is a well-reported entity in Chinese medical literature,
      however, only a small number of instances have been proven by molecular
      diagnosis. Most of the features resemble what is known in other countries. The
      highly predominant motor presentation, and the higher male prevalence as well as
      the apparent concentration in Northern China may be due to observational bias.
      There is therefore a need to prospectively examine cohorts of patients with
      appropriate comprehensive assessment tools including genetic testing.

PMID- 22453899
TI  - Repression of nuclear CELF activity can rescue CELF-regulated alternative
      splicing defects in skeletal muscle models of myotonic dystrophy.
AB  - Myotonic dystrophy type 1 (DM1) is caused by the expansion of CUG repeats in the
      3' UTR of DMPK transcripts. DM1 pathogenesis has been attributed in part to
      alternative splicing dysregulation via elevation of CUG-BP, Elav-like family
      member 1 (CELF1). Several therapeutic approaches have been tested in cells and
      mice, but no previous studies had specifically targeted CELF1. Here, we show that
      repressing CELF activity rescues CELF-dependent alternative splicing in cell
      culture and transgenic mouse models of DM1. CELF-independent splicing, however,
      remained dysregulated. These data highlight both the potential and limitations of
      targeting CELF1 for the treatment of DM1.

PMID- 22453900
TI  - Quantification of the heat wave effect on mortality in nine French cities during
      summer 2006.
AB  - BACKGROUND: July 2006 was the first major heat wave in France after the creation
      of a heat prevention plan. Understanding its impacts on health will help
      improving the efficiency of this plan. We assessed the mortality impact of the
      heat wave, and investigated the influence of the heat prevention plan. METHODS:
      The study focused on nine French cities. A Poisson regression model was used to
      analyze the correlation between temperature, air quality and mortality. An
      additional spline of time was introduced to capture an additional heat wave
      effect. Heat-action days defined by the prevention plan were introduced as a
      dummy variable. RESULTS: 411 extra deaths were observed in the nine cities during
      the 2006 heat wave. Unlike the 2003 heat wave, no additional heat wave effect was
      observed in 2006. The maximum daily relative risk of mortality varied from 1.45
      in Strasbourg (IC 95% [1.01-2.08]) to 1.04 in Lille (IC 95% [0.92-1.18]). The
      impact on mortality of the implementation of heat-action days was non-significant
      and highly variable depending on the cities, with a combined excess of relative
      risk of -3.3% (IC 95% [-10.3%; 4.4%]). CONCLUSIONS: Although no specific heat
      wave effect was observed, warm temperatures and air pollution were still
      responsible for a significant excess mortality in France. The absence of a
      specific heat wave effect may be partly explained by the prevention plan. It may
      also indicate that higher temperatures are required to observe a mortality
      outburst.

PMID- 22453901
TI  - Standard maximum likelihood analyses of alignments with gaps can be statistically
      inconsistent.
AB  - BackgroundMost statistical methods for phylogenetic estimation in use today treat
      a gap (generally representing an insertion or deletion, i.e., indel) within the
      input sequence alignment as missing data. However, the statistical properties of
      this treatment of indels have not been fully investigated.ResultsWe prove that
      maximum likelihood phylogeny estimation, treating indels as missing data, can be
      statistically inconsistent for a general (and rather simple) model of sequence
      evolution, even when given the true alignment. Therefore, accurate phylogeny
      estimation cannot be guaranteed for maximum likelihood analyses, even given
      arbitrarily long sequences, when indels are present and treated as missing
      data.ConclusionsOur result shows that the standard statistical techniques used to
      estimate phylogenies from sequence alignments may have unfavorable statistical
      properties, even when the sequence alignment is accurate and the assumed
      substitution model matches the generation model. This suggests that the recent
      research focus on developing statistical methods that treat indel events properly
      is an important direction for phylogeny estimation.

PMID- 22453902
TI  - DuchenneConnect Registry Report.
AB  - Research activity in Duchenne/Becker muscular dystrophy has surged in recent
      years, requiring robust information networks to support ongoing development.
      Established by Parent Project Muscular Dystrophy in late 2007, DuchenneConnect
      was created to bridge the information gap between care providers, researchers and
      the patient community, thereby addressing medical care needs and accelerating the
      pace of therapeutic advancements. This report represents the first in a new
      series that will be regularly shared by DuchenneConnect and PPMD. Data in this
      report was collected through June 2011.

PMID- 22453903
TI  - Cholera ante portas - The re-emergence of cholera in Kinshasa after a ten-year
      hiatus.
AB  - BACKGROUND: Cholera is an endemic disease in certain well-defined areas in the
      east of the Democratic Republic of Congo (DRC). The west of the country,
      including the mega-city Kinshasa, has been free of cases since mid 2001 when the
      last outbreak ended. METHODS AND FINDINGS: We used routinely collected passive
      surveillance data to construct epidemic curves of the cholera cases and map the
      spatio-temporal progress of the disease during the first 47 weeks of 2011. We
      compared the spatial distribution of disease spread to that which occurred in the
      last cholera epidemic in Kinshasa between 1996 and 2001. To better understand
      previous determinants of cholera spread in this region, we conducted a
      correlation analysis to assess the impact of rainfall on weekly health zone
      cholera case counts between December 1998 and March 2001 and a Generalized Linear
      Model (GLM) regression analysis to identify factors that have been associated
      with the most vulnerable health zones within Kinshasa between October 1998 and
      June 1999. In February 2011, cholera reemerged in a region surrounding Kisangani
      and gradually spread westwards following the course of the Congo River to
      Kinshasa, home to 10 million people. Ten sampled isolates were confirmed to be
      Vibrio cholerae O1, biotype El Tor, serotype Inaba, resistant to trimethoprim
      sulfa, furazolidone, nalidixic acid, sulfisoxaole, and streptomycin, and
      intermediate resistant to Chloramphenicol. An analysis of a previous outbreak in
      Kinshasa shows that rainfall was correlated with case counts and that health zone
      population densities as well as fishing and trade activities were predictors of
      case counts. CONCLUSION: Cholera is particularly difficult to tackle in the DRC.
      Given the duration of the rainy season and increased riverine traffic from the
      eastern provinces in late 2011, we expect further increases in cholera in the
      coming months and especially within the mega-city Kinshasa. We urge all partners
      involved in the response to remain alert.Didier Bompangue and Silvan Vesenbeckh
      contributed equally to this work. *corresponding author: Silvan Vesenbeckh,
      Harvard School of Public Health (vesenbeckh@gmail.com)Didier Bompangue is
      Associate Professor in the Department of Microbiology (University of Kinshasa)
      andEpidemiologist in the DRC Ministry of Health. He was involved in the
      investigations of the described outbreak since February 2011.

PMID- 22453904
TI  - Ameliorative effect of supplementation with L-glutamine on oxidative stress, DNA
      damage, cell viability and hepatotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p
      dioxin in rat hepatocyte cultures.
AB  - The most potent of the dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a
      persistent and ubiquitous environmental contaminant. And the health impact of
      exposure to TCDD is of great concern to the general public. Recent data indicate
      that L-glutamine (Gln) has antioxidant properties and may influence
      hepatotoxicity. The objective of the present study was undertaken to explore the
      effectiveness of Gln in alleviating the hepatotoxicity of TCDD on primary
      cultured rat hepatocytes. Gln (0.5, 1 and 2 mM) was added to cultures alone or
      simultaneously with TCDD (0.005 and 0.01 mM). The hepatocytes were treated with
      TCDD and Gln for 48 h. Then cell viability was detected by [3-(4,5-dimethyl
      thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate
      dehydrogenase (LDH) release, while total antioxidant capacity (TAC), total
      glutathione (TGSH) and total oxidative stress (TOS) levels were determined to
      evaluate the oxidative injury. The DNA damage was also analyzed by liver
      micronucleus assay (MN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT
      and LDH assays showed that TCDD decreased cell viability but not L-glutamine.
      TCDD also increased TOS level in rat hepatocytes and significantly decreased TAC
      and TGSH levels. On the basis of increasing doses, the dioxin in a dose-dependent
      manner caused significant increases of micronucleated hepatocytes (MNHEPs) and 8
      OH-dG as compared to control culture. Whereas, in cultures exposured with Gln
      alone, TOS levels were not changed and TAC and TGSH together were significantly
      increased in dose-dependent fashion. The presence of Gln with TCDD modulated the
      hepatotoxic effects of TCDD on primary hepatocytes cultures. Noteworthy, Gln has
      a protective effect against TCDD-mediated DNA damages. As conclusion, we reported
      here an increased potential therapeutic significance of L-glutamine in TCDD
      mediated hepatic injury for the first time.

PMID- 22453906
TI  - Phosphorylation sites of higher stoichiometry are more conserved.

PMID- 22453905
TI  - Modulation of ATP-induced LTP by cannabinoid receptors in rat hippocampus.
AB  - Cannabinoids exert powerful action on various forms of synaptic plasticity. These
      retrograde messengers modulate GABA and glutamate release from presynaptic
      terminals by acting on presynaptic CB1 receptors. In particular, they inhibit
      long-term potentiation (LTP) elicited by electrical stimulation of excitatory
      pathways in rat hippocampus. Recently, LTP of the field excitatory postsynaptic
      potential (fEPSP) induced by exogenous ATP has been thoroughly explored. The
      present study demonstrates that cannabinoids inhibit ATP-induced LTP in
      hippocampal slices of rat. Administration of 10 MUM of ATP led to strong
      inhibition of fEPSPs in CA1/CA3 hippocampal synapses. Within 40 min after ATP
      removal from bath solution, robust LTP was observed (fEPSP amplitude comprised
      130.1 +/- 3.8% of control, n = 10). This LTP never appeared when ATP was applied
      in addition to cannabinoid receptor agonist WIN55,212-2 (100 nM). Selective CB1
      receptor antagonist, AM251 (500 nM), completely abolished this effect of
      WIN55,212-2. Our data indicate that like canonical LTP elicited by electrical
      stimulation, ATP-induced LTP is under control of CB1 receptors.

PMID- 22453909
TI  - Magnetic sequencing.

PMID- 22453910
TI  - Neighboring-gene effect: a genetic uncertainty principle.

PMID- 22453911
TI  - Protein interaction data curation: the International Molecular Exchange (IMEx)
      consortium.
AB  - The International Molecular Exchange (IMEx) consortium is an international
      collaboration between major public interaction data providers to share literature
      curation efforts and make a nonredundant set of protein interactions available in
      a single search interface on a common website (http://www.imexconsortium.org/).
      Common curation rules have been developed, and a central registry is used to
      manage the selection of articles to enter into the dataset. We discuss the
      advantages of such a service to the user, our quality-control measures and our
      data-distribution practices.

PMID- 22453912
TI  - Atrial fibrillation and diabetes mellitus. Correlation, co-existence, and
      coagulation therapy.
AB  - Epidemiological studies have reported on the association between diabetes
      mellitus (DM) and subsequent risk of atrial fibrillation (AF) with inconsistent
      results. Individuals with DM present with an increased risk (approximate 40%) of
      subsequent AF compared with unaffected individuals, but the mechanisms underlying
      the relationship between DM and AF remains speculative. Both entities share
      common risk factors and, thus, seem to be closely associated with each other.
      Obviously, the quality of glycemic control is directly related with the risk for
      AF; the risk is higher with longer duration of treated diabetes and poorer
      glycemic control. Future research should identify approaches to reduce the risk
      of AF in people with diabetes by means of consequent screening and anti
      coagulation therapy.

PMID- 22453913
TI  - [SREBP-1 and fatty liver. Clinical relevance for diabetes, obesity, dyslipidemia
      and atherosclerosis].
AB  - Insulin resistance and visceral fat distribution usually play a major role in the
      development of clinical aspects of the metabolic syndrome, such as dyslipidemia,
      diabetes and atherosclerosis. In this review, the focus will be on some novel
      relationships with a fatty liver, for which susceptibility appears to be mediated
      by the activity of transcription factors, such as sterol regulatory element
      binding protein 1 (SREBP-1). In addition to this molecular aspect therapeutic
      life-style modifications, such as weight reduction which are associated with
      increased insulin sensitivity and a decrease of fat in the liver will be
      discussed.

PMID- 22453914
TI  - Selective droplet coalescence using microfluidic systems.
AB  - We report a microfluidic approach, which allows selective and controlled 1 : 1, 2
      : 1 or 3 : 1 droplet fusion. A surfactant-stabilized droplet with an interfacial
      surfactant coverage, Gamma, of >98% will fuse spontaneously with a second droplet
      when Gamma of the latter droplet is <16%. However, when Gamma of the second
      droplet is ~66%, the two droplets will not fuse, unless they have previously been
      brought into contact for critical time tau. Therefore, controlling the number of
      droplets in contact for time tau allows precise control over the number of fused
      droplets. We have demonstrated efficient (proportion of droplets coalesced p(c) =
      1.0, n > 1000) and selective 1 : 1, 2 : 1 or 3 : 1 droplet fusion (proportion of
      correctly fused droplets p(s) > 0.99, n > 1000). Coalescence in this regime is
      induced by hydrodynamic flow causing interface separation and is efficient at
      different Ca numbers and using different dispersed phases, continuous phases and
      surfactants. However, when Gamma of the second droplet is ~96% coalescence is no
      longer observed. Droplet-based microfluidic systems, in which each droplet
      functions as an independent microreactor, are proving a promising tool for a wide
      range of ultrahigh-throughput applications in biology and chemistry. The addition
      of new reagents to pre-formed droplets is critical to many of these applications
      and we believe the system described here is a simple and flexible method to do
      so, as well as a new tool to study interfacial stability phenomena.

PMID- 22453915
TI  - Heterogeneity in clonal nature in the smoldering subtype of adult T-cell
      leukemia: continuity from carrier status to smoldering ATL.
AB  - To better understand indeterminate HTLV-1 carriers and smoldering (SM) subtype of
      adult T-cell leukemia (ATL), HTLV-1 proviral integrated status, proviral load
      (PVL) and ATL-related biomarkers were examined in 57 smoldering cases, including
      unusual carriers with a percentage of ATL-like cells. We found that according to
      Southern blot hybridization analytic features, 28 patients with SM ATL could be
      divided into 3 groups consisting of 16 (57.4%) patients with a monoclonal band, 6
      (21.4%) with oligoclonal bands and the remaining 6 with smears. Although no
      clinical differences were observed among the 3 SM subtypes, HTLV-1-infected CD4 T
      cell counts increased in order of poly-, oligo- and monoclonal subtypes. This
      trend began in the carrier stage and also was observed in PVL, CD25 and CCR4,
      indicating that a clone consisting of leukemic phenotypic cells was continuously
      growing. Moreover, the antigen modulation rates of CD26 and CD7 and the
      increasing rate of CD25 and CCR4 cells were closely correlated to growing clonal
      size, indicating that these markers had the possibility to predict a monoclonal
      band. In particular, CD26 or the ratio of CD26/CD25 had a validity differential
      for leukemic nature and predictive detection of clonal band. Conclusively, the
      present study shows that smoldering ATL is heterogeneous in the leukemogenic
      process, and the behavior of CD26 plays a central role in the evolution from
      early occult to overt smoldering ATL.

PMID- 22453916
TI  - High frequency of inherited variants in the MEFV gene in patients with
      hematologic neoplasms: a genetic susceptibility?
AB  - Familial Mediterranean fever is an autosomal recessive disease occurring in
      populations originating from the Mediterranean basin. This autoinflammatory
      syndrome is caused by mutations in the Mediterranean FeVer (MEFV) gene. MEFV
      encodes a 781 amino acid protein known as pyrin. Pyrin is an important modulator
      of apoptosis, inflammation, and cytokine processing. In more recent pilot
      studies, inherited variant analysis of the MEFV gene in patients with hematologic
      neoplasm showed an unexpectedly high frequency of these variants in the gene.
      Here, we summarize the current state of knowledge of the relationship between
      inherited variants in the MEFV gene and hematologic neoplasms. Although no single
      underlying defect could be targeted in all hematologic neoplasms, it will be
      important to fully exploit the mechanisms underlying the neoplasm promoting role
      of inherited variants in MEFV. However, it is unclear how inherited variants in
      the MEFV gene are associated with tumor susceptibility or promotion in
      hematologic neoplasms. Further investigations are needed to determine the actual
      role of the MEFV gene in pathogenesis of these neoplasms.

PMID- 22453917
TI  - alpha-Synuclein controls mitochondrial calcium homeostasis by enhancing
      endoplasmic reticulum-mitochondria interactions.
AB  - alpha-Synuclein has a central role in Parkinson disease, but its physiological
      function and the mechanism leading to neuronal degeneration remain unknown.
      Because recent studies have highlighted a role for alpha-synuclein in regulating
      mitochondrial morphology and autophagic clearance, we investigated the effect of
      alpha-synuclein in HeLa cells on mitochondrial signaling properties focusing on
      Ca(2+) homeostasis, which controls essential bioenergetic functions. By using
      organelle-targeted Ca(2+)-sensitive aequorin probes, we demonstrated that alpha
      synuclein positively affects Ca(2+) transfer from the endoplasmic reticulum to
      the mitochondria, augmenting the mitochondrial Ca(2+) transients elicited by
      agonists that induce endoplasmic reticulum Ca(2+) release. This effect is not
      dependent on the intrinsic Ca(2+) uptake capacity of mitochondria, as measured in
      permeabilized cells, but correlates with an increase in the number of endoplasmic
      reticulum-mitochondria interactions. This action specifically requires the
      presence of the C-terminal alpha-synuclein domain. Conversely, alpha-synuclein
      siRNA silencing markedly reduces mitochondrial Ca(2+) uptake, causing profound
      alterations in organelle morphology. The enhanced accumulation of alpha-synuclein
      into the cells causes the redistribution of alpha-synuclein to localized foci
      and, similarly to the silencing of alpha-synuclein, reduces the ability of
      mitochondria to accumulate Ca(2+). The absence of efficient Ca(2+) transfer from
      endoplasmic reticulum to mitochondria results in augmented autophagy that, in the
      long range, could compromise cellular bioenergetics. Overall, these findings
      demonstrate a key role for alpha-synuclein in the regulation of mitochondrial
      homeostasis in physiological conditions. Elevated alpha-synuclein expression
      and/or eventually alteration of the aggregation properties cause the
      redistribution of the protein within the cell and the loss of modulation on
      mitochondrial function.

PMID- 22453918
TI  - The iron chelators Dp44mT and DFO inhibit TGF-beta-induced epithelial-mesenchymal
      transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1).
AB  - The epithelial-mesenchymal transition (EMT) is a key step for cancer cell
      migration, invasion, and metastasis. Transforming growth factor-beta (TGF-beta)
      regulates the EMT and the metastasis suppressor gene, N-myc downstream-regulated
      gene-1 (NDRG1), could play a role in regulating the TGF-beta pathway. NDRG1
      expression is markedly increased after chelator-mediated iron depletion via
      hypoxia-inducible factor 1alpha-dependent and independent pathways (Le, N. T. and
      Richardson, D. R. (2004) Blood 104, 2967-2975). Moreover, novel iron chelators
      show marked and selective anti-tumor activity and are a potential new class of
      anti-metabolites. Considering this, the current study investigated the
      relationship between NDRG1 and the EMT to examine if iron chelators can inhibit
      the EMT via NDRG1 up-regulation. We demonstrated that TGF-beta induces the EMT in
      HT29 and DU145 cells. Further, the chelators, desferrioxamine (DFO) and di-2
      pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), inhibited the TGF-beta
      induced EMT by maintaining E-cadherin and beta-catenin, at the cell membrane. We
      then established stable clones with NDRG1 overexpression and knock-down in HT29
      and DU145 cells. These data showed that NDRG1 overexpression maintained membrane
      E-cadherin and beta-catenin and inhibited TGF-beta-stimulated cell migration and
      invasion. Conversely, NDRG1 knock-down caused morphological changes from an
      epithelial- to fibroblastic-like phenotype and also increased migration and
      invasion, demonstrating NDRG1 knockdown induced the EMT and enhanced TGF-beta
      effects. We also investigated the mechanisms involved and showed the TGF
      beta/SMAD and Wnt pathways were implicated in NDRG1 regulation of E-cadherin and
      beta-catenin expression and translocation. This study demonstrates that chelators
      inhibit the TGF-beta-induced EMT via a process consistent with NDRG1 up
      regulation and elucidates the mechanism of their activity.

PMID- 22453919
TI  - GTP-binding protein-like domain of AGAP1 is protein binding site that
      allosterically regulates ArfGAP protein catalytic activity.
AB  - AGAPs are a subtype of Arf GTPase-activating proteins (GAPs) with 11 members in
      humans. In addition to the Arf GAP domain, the proteins contain a G-protein-like
      domain (GLD) with homology to Ras superfamily proteins and a PH domain. AGAPs
      bind to clathrin adaptors, function in post Golgi membrane traffic, and have been
      implicated in glioblastoma. The regulation of AGAPs is largely unexplored. Other
      enzymes containing GTP binding domains are regulated by nucleotide binding.
      However, nucleotide binding to AGAPs has not been detected. Here, we found that
      neither nucleotides nor deleting the GLD of AGAP1 affected catalysis, which led
      us to hypothesize that the GLD is a protein binding site that regulates GAP
      activity. Two-hybrid screens identified RhoA, Rac1, and Cdc42 as potential
      binding partners. Coimmunoprecipitation confirmed that AGAP1 and AGAP2 can bind
      to RhoA. Binding was mediated by the C terminus of RhoA and was independent of
      nucleotide. RhoA and the C-terminal peptide from RhoA increased GAP activity
      specifically for the substrate Arf1. In contrast, a C-terminal peptide from Cdc42
      neither bound nor activated AGAP1. Based on these results, we propose that AGAPs
      are allosterically regulated through protein binding to the GLD domain.

PMID- 22453920
TI  - Dual role of the molybdenum cofactor biosynthesis protein MOCS3 in tRNA
      thiolation and molybdenum cofactor biosynthesis in humans.
AB  - We studied two pathways that involve the transfer of persulfide sulfur in humans,
      molybdenum cofactor biosynthesis and tRNA thiolation. Investigations using human
      cells showed that the two-domain protein MOCS3 is shared between both pathways.
      MOCS3 has an N-terminal adenylation domain and a C-terminal rhodanese-like
      domain. We showed that MOCS3 activates both MOCS2A and URM1 by adenylation and a
      subsequent sulfur transfer step for the formation of the thiocarboxylate group at
      the C terminus of each protein. MOCS2A and URM1 are beta-grasp fold proteins that
      contain a highly conserved C-terminal double glycine motif. The role of the
      terminal glycine of MOCS2A and URM1 was examined for the interaction and the
      cellular localization with MOCS3. Deletion of the C-terminal glycine of either
      MOCS2A or URM1 resulted in a loss of interaction with MOCS3. Enhanced cyan
      fluorescent protein and enhanced yellow fluorescent protein fusions of the
      proteins were constructed, and the fluorescence resonance energy transfer
      efficiency was determined by the decrease in the donor lifetime. The cellular
      localization results showed that extension of the C terminus with an additional
      glycine of MOCS2A and URM1 altered the localization of MOCS3 from the cytosol to
      the nucleus.

PMID- 22453921
TI  - The FF4 and FF5 domains of transcription elongation regulator 1 (TCERG1) target
      proteins to the periphery of speckles.
AB  - Transcription elongation regulator 1 (TCERG1) is a human factor implicated in
      interactions with the spliceosome as a coupler of transcription and splicing. The
      protein is highly concentrated at the interface between speckles (the
      compartments enriched in splicing factors) and nearby transcription sites. Here,
      we identified the FF4 and FF5 domains of TCERG1 as the amino acid sequences
      required to direct this protein to the periphery of nuclear speckles, where
      coordinated transcription/RNA processing events occur. Consistent with our
      localization data, we observed that the FF4 and FF5 pair is required to fold in
      solution, thus suggesting that the pair forms a functional unit. When added to
      heterologous proteins, the FF4-FF5 pair is capable of targeting the resulting
      fusion protein to speckles. This represents, to our knowledge, the first
      description of a targeting signal for the localization of proteins to sites
      peripheral to speckled domains. Moreover, this "speckle periphery-targeting
      signal" contributes to the regulation of alternative splicing decisions of a
      reporter pre-mRNA in vivo.

PMID- 22453922
TI  - Kaposi sarcoma-associated herpesvirus vIRF-3 protein binds to F-box of Skp2
      protein and acts as a regulator of c-Myc protein function and stability.
AB  - The Kaposi sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi
      sarcoma, body cavity-based lymphoma, and Castleman disease. vIRF-3 is a KSHV
      latent gene that is critical for proliferation of KSHV-positive lymphoid cells.
      Furthermore, vIRF-3 contributes to KSHV-associated pathogenesis by stimulating c
      Myc transcription activity. Here we show that vIRF-3 can associate with Skp2, a
      key component of the SCF(skp2) ubiquitin ligase complex. Skp2 is a
      transcriptional co-factor for c-Myc that was shown to regulate the stability of c
      Myc protein as well as c-Myc-dependent transcription. In this study, we show that
      vIRF-3 binds to the F-box of Skp2 and recruits it to c-Myc-regulated promoters to
      activate c-Myc-dependent transcription. Additionally, cells overexpressing vIRF-3
      exhibit higher levels of c-Myc ubiquitylation, suggesting that ubiquitylation is
      necessary for c-Myc-mediated transcription. Moreover, vIRF-3 can stabilize the c
      Myc protein by increasing its half-life. Collectively, these results indicate
      that vIRF-3 can effectively manipulate c-Myc stability and function and thus
      contribute to c-Myc-induced KSHV-associated lymphomagenesis.

PMID- 22453924
TI  - Novel mutation in spectrin-like repeat 1 of dystrophin central domain causes
      protein misfolding and mild Becker muscular dystrophy.
AB  - Mutations in the dystrophin gene without disruption of the reading frame often
      lead to Becker muscular dystrophy, but a genotype/phenotype correlation is
      difficult to establish. Amino acid substitutions may disrupt binding capacities
      of dystrophin and have a major impact on the functionality of this protein. We
      have identified two brothers (ages 8 and 10 years) with very mild proximal
      weakness, recurrent abdominal pain, and moderately elevated serum creatine kinase
      levels. Gene sequencing revealed a novel mutation in exon 11 of the dystrophin
      gene (c.1280T>C) leading to a L427P amino acid substitution in repeat 1 of the
      central rod domain. Immunostaining of skeletal muscle showed weak staining of the
      dystrophin region encoded by exons 7 and 8 corresponding to the end of the actin
      binding domain 1 and the N-terminal part of hinge 1. Spectrofluorescence and
      circular dichroism analysis of the domain repeat 1-2 (R1-2) revealed partial
      misfolding of the L427P mutated protein as well as a reduced refolding rate after
      denaturation. Based on computational homology models of the wild-type and mutated
      R1-2, a molecular dynamics study showed an alteration in the flexibility of the
      structure, which also strongly affects the conformational space available in the
      N-terminal region of the fragment. Our results suggest that this missense
      mutation hinders the dynamic properties of the entire N-terminal region of
      dystrophin.

PMID- 22453923
TI  - Potential biological functions of cytochrome P450 reductase-dependent enzymes in
      small intestine: novel link to expression of major histocompatibility complex
      class II genes.
AB  - NADPH-cytochrome P450 reductase (POR) is essential for the functioning of
      microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. The
      biological roles of the POR-dependent enzymes in the intestine have not been
      defined, despite the wealth of knowledge on the biochemical properties of the
      various oxygenases. In this study, cDNA microarray analysis revealed significant
      changes in gene expression in enterocytes isolated from the small intestine of
      intestinal epithelium-specific Por knock-out (named IE-Cpr-null) mice compared
      with that observed in wild-type (WT) littermates. Gene ontology analyses revealed
      significant changes in terms related to P450s, transporters, cholesterol
      biosynthesis, and, unexpectedly, antigen presentation/processing. The genomic
      changes were confirmed at either mRNA or protein level for selected genes,
      including those of the major histocompatibility complex class II (MHC II).
      Cholesterol biosynthetic activity was greatly reduced in the enterocytes of the
      IE-Cpr-null mice, as evidenced by the accumulation of the lanosterol metabolite,
      24-dihydrolanosterol. However, no differences in either circulating or enterocyte
      cholesterol levels were observed between IE-Cpr-null and WT mice. Interestingly,
      the levels of the cholesterol precursor farnesyl pyrophosphate and its derivative
      geranylgeranyl pyrophosphate were also increased in the enterocytes of the IE-Cpr
      null mice. Furthermore, the expression of STAT1 (signal transducer and activator
      of transcription 1), a downstream target of geranylgeranyl pyrophosphate
      signaling, was enhanced. STAT1 is an activator of CIITA, the class II
      transactivator for MHC II expression; CIITA expression was concomitantly
      increased in IE-Cpr-null mice. Overall, these findings provide a novel and
      mechanistic link between POR-dependent enzymes and the expression of MHC II genes
      in the small intestine.

PMID- 22453926
TI  - Social learning and acquired recognition of a predator by a marine fish.
AB  - Predation is known to influence the distribution of behavioural traits among prey
      individuals, populations and communities over both evolutionary and ecological
      time scales. Prey have evolved mechanisms of rapidly learning the identity of
      predators. Chemical cues are often used by prey to assess predation risk
      especially in aquatic systems where visual cues are unreliable. Social learning
      is a method of threat assessment common among a variety of freshwater fish taxa,
      which incorporates chemosensory information. Learning predator identities through
      social learning is beneficial to naive individuals as it eliminates the need for
      direct interaction with a potential threat. Although social learning is
      widespread throughout the animal kingdom, no research on the use of this
      mechanism exists for marine species. In this study, we examined the role of
      social learning in predator recognition for a tropical damselfish, Acanthochromis
      polyacanthus. This species was found to not only possess and respond to
      conspecific chemical alarm cues, but naive individuals were able to learn a
      predators' identity from experienced individuals, the process of social learning.
      Fish that learned to associate risk with the olfactory cue of a predator
      responded with the same intensity as conspecifics that were exposed to a chemical
      alarm cue from a conspecific skin extract.

PMID- 22453925
TI  - Graphene-based composite materials beneficial to wound healing.
AB  - We use electrospinning to prepare chitosan-PVA nanofibers containing graphene.
      The nanofibers can be directly used in wound healing: graphene, as an
      antibacterial material, can be beneficial for this. A possible antibacterial
      mechanism for graphene is presented.

PMID- 22453927
TI  - Bariatric surgery decision making challenges: the stability of teens' decisions
      and the treatment failure paradox.
AB  - PURPOSE: Criteria for adolescent bariatric surgery include failure of >=6 months
      of organized weight loss attempts. We wished to explore whether adolescents,
      initially wanting surgery, change their mind during a 6-month weight loss program
      and how many meet the treatment failure criterion. METHODS: A retrospective chart
      review of adolescents enrolled in a weight loss program between 3/2007 and
      2/2009. RESULTS: Twenty-one (13 % of total patients) initially wanted bariatric
      surgery. Most were Medicaid enrollees (70 %), female (85 %), and white (60 %).
      The mean age was 15 years and mean BMI was 51 (range 36-71). Five did not meet
      BMI, comorbidity, or psychological criteria for surgery. Eight lost weight and
      therefore did not meet the treatment failure criterion. Of these, seven no longer
      wanted surgery. Eight did not lose weight and therefore met the treatment failure
      criterion; five of these decided against surgery due to difficulty in making
      recommended lifestyle changes. CONCLUSION: Most patients initially wanting
      bariatric surgery changed their minds. The treatment failure criterion presented
      a paradox, because most patients who met the criterion exhibited difficulty in
      making the lifestyle changes. To aid provider/patient decisions about bariatric
      surgery, further work should explore the criteria for surgery and stability of
      adolescents' decisions regarding bariatric surgery.

PMID- 22453928
TI  - Sex differences in children with autism spectrum disorder identified within a
      high-risk infant cohort.
AB  - Sex differences were examined in 3-year-olds with autism spectrum disorders (ASD)
      ascertained from a high-risk cohort, and high- and low-risk comparison groups.
      Participants included 319 high-risk siblings and 129 low-risk controls. Eighty
      five siblings were diagnosed with ASD, including 57 of 176 boys (32.4 %) and 28
      of 143 girls (19.6 %), implying a relative odds of ASD of 1.65 in boys versus
      girls. There were modest sex differences on cognitive and adaptive skills and ASD
      symptom severity at age 3, but differences between boys and girls with ASD
      mirrored those in the non-ASD groups. The lower than expected male-to-female
      ratio, and the relatively high cognitive level among diagnosed children, suggest
      that we have identified an unanticipated number of higher-functioning girls with
      ASD.

PMID- 22453929
TI  - 18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: synthesis from 2,4
      dinitrobenzamide and tosylate precursors and comparative biological evaluation
      for tumor imaging with positron emission tomography.
AB  - We previously reported 18F-labeled pyrazolo[1,5-a]pyrimidine derivatives: 7-(2
      [18F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([18F]1)
      and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[18F]fluoro
      4-nitro- benzamide ([18F]2). Preliminary biodistribution experiments of both
      compounds showed s slow clearance rate from excretory tissues which warranted
      further investigation for tumor imaging with PET. Here we modified [18F]1 and
      [18F]2 by introducing polar groups such as ester, hydroxyl and carboxyl and
      developed three additional 18F-18 labeled pyrazolo[1,5-a] pyrimidine derivatives:
      (3-Cyano-7-(2-[18F]fluoroethylamino)pyrazolo[1,5-a]-pyrimidin-5- yl)methyl
      acetate ([18F]3), 7-(2-[18F]fluoroethylamino)-5-(hydroxymethyl)pyrazolo[1,5-a]-
      pyrimidine-3-carbonitrile ([18F]4) and (S)-6-(3-cyano-5-methylpyrazolo[1,5
      a]pyrimidin-7-ylamino)-2-(2-[18F]fluoro-4-nitrobenzamido)hexanoic acid ([18F]5).
      The radiolabeled probes were synthesized by nucleophilic substitution of the
      corresponding tosylate and nitro precursors with 18F-fluoride. In Vitro studies
      showed higher uptake of [18F]3 and [18F]4 than that of [18F]5 by S180 tumor
      cells. In Vivo biodistribution studies in mice bearing S180 tumors showed that
      the uptake of both [18F]3 and [18F]4 in tumors displayed an increasing trend
      while the uptake of [18F]5 in tumor decreased through the course of the 120 min
      study. This significant difference in tumor uptake was also found between [18F]1
      and [18F]2. Thus, we compared the biological behavior of the five tracers and
      reported the tumor uptake kinetic differences between 2-[18F]fluoroethylamino-
      and 2-[18F]fluoro-4-nitro- benzamidopyrazolo[1,5-a] pyrimidine derivatives.

PMID- 22453930
TI  - Factors affecting the physical properties of edible composite film prepared from
      zein and wheat gluten.
AB  - The effects of zein ratio, concentration of glycerol, liquid-solid ratio, ethanol
      concentration, pH and heat-treatment temperature on the properties of zein/wheat
      gluten composite films were researched. The results showed that elongation (E)
      increased with an increase in glycerol or ethanol concentrations, but it first
      increased and then decreased with increasing zein/wheat gluten ratio, heat
      treatment temperature, pH and the ratio of liquid to solid; Tensile strength (TS)
      increased with the increase in heat-treatment temperature and pH, and decreased
      with the increase in glycerol or ethanol concentrations, and it reached a maximum
      value when the ratio of zein/wheat gluten was 20%, but had a minimum value when
      the ratio of liquid to solid was 8:1; Water Vapor Permeability (WVP) increased
      with an increase of glycerol concentration and the ratio of liquid to solid and
      ethanol concentration, but it decreased with increasing zein/wheat gluten ratio,
      heat treatment temperature, and pH of the film forming solution.

PMID- 22453931
TI  - Protective effect of ischemic postconditioning against ischemia reperfusion
      induced myocardium oxidative injury in IR rats.
AB  - Brief episodes of myocardial ischemia-reperfusion (IR) employed during
      reperfusion after a prolonged ischemic insult may attenuate the total ischemia
      reperfusion injury. This phenomenon has been termed ischemic postconditioning. In
      the present study, we studied the possible effect of ischemic postconditioning on
      an ischemic reperfusion (IR)-induced myocardium oxidative injury in rat model.
      Results showed that ischemic postconditioning could improve arrhythmia cordis,
      reduce myocardium infarction and serum creatin kinase (CK), lactate dehydrogenase
      (LDH) and aspartate transaminase (AST) activities in IR rats. In addition,
      ischemic postconditioning could still decrease myocardium malondialdehyde (MDA)
      level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione
      reductase (GR) activities. It can be concluded that ischemic postconditioning
      possesses strong protective effects against ischemia reperfusion-induced
      myocardium oxidative injury in IR rats.

PMID- 22453932
TI  - DNA MMR systems, microsatellite instability and antioxidant activity variations
      in two species of wild bats: Myotis velifer and Desmodus rotundus, as possible
      factors associated with longevity.
AB  - The accumulation of oxidative damage to biomolecules, such as DNA, is known to
      induce alterations in the cell's mechanisms and structure that might lead to the
      aging process. DNA mismatch repair system (MMR) corrects base mismatches
      generated during DNA replication that have escaped the proofreading process. In
      addition, antioxidant enzymes can reduce reactive oxygen species effects in order
      to protect cells from oxidizing damage. In order to determine the importance of
      these associated factors during the aging process, in this study, levels of MMR
      proteins MSH2 and MLH1, as well as microsatellite markers, were compared in
      liver, lung, and brain of juvenile, adult, and old, both female and male,
      individuals from two species of wild bats: the short-lived Myotis velifer and the
      longer lived Desmodus rotundus. Catalase, glutathione peroxidase, and superoxide
      dismutase were also analyzed to determine if the antioxidant protection
      correlates negatively with DNA damage. Antioxidant activities were higher in the
      longer lived D. rotundus than in M. velifer. Furthermore, old M. velifer but not
      old D. rotundus bats had reduced MMR levels and increased microsatellite
      instability. Therefore, although our results correlate the reduced MMR
      efficiency, the deficient antioxidant activity, and the increase in DNA damage
      with the aging process, this is not always true for all living organisms.

PMID- 22453934
TI  - Neuromuscular adaptations to concurrent training in the elderly: effects of
      intrasession exercise sequence.
AB  - The aim of this study was investigate the effects of different intrasession
      exercise orders in the neuromuscular adaptations induced by concurrent training
      in elderly. Twenty-six healthy elderly men (64.7 +/- 4.1 years), were placed into
      two concurrent training groups: strength prior to (SE, n = 13) or after (ES, n =
      13) endurance training. Subjects trained strength and endurance training during
      12 weeks, three times per week performing both exercise types in the same
      training session. Upper and lower body one maximum repetition test (1RM) and
      lower-body isometric peak torque (PTiso) and rate of force development were
      evaluated as strength parameters. Upper and lower body muscle thickness (MT) was
      determined by ultrasonography. Lower-body maximal surface electromyographic
      activity of vastus lateralis and rectus femoris muscles (maximal
      electromyographic (EMG) amplitude) and neuromuscular economy (normalized EMG at
      50 % of pretraining PTiso) were determined. Both SE and ES groups increased the
      upper- and lower-body 1RM, but the lower-body 1RM increases observed in the SE
      was higher than ES (35.1 +/- 12.8 vs. 21.9 +/- 10.6 %, respectively; P < 0.01).
      Both SE and ES showed MT increases in all muscles evaluated, with no differences
      between groups. In addition, there were increases in the maximal EMG and
      neuromuscular economy of vastus lateralis in both SE and ES, but the
      neuromuscular economy of rectus femoris was improved only in SE (P < 0.001).
      Performing strength prior to endurance exercise during concurrent training
      resulted in greater lower-body strength gains as well as greater changes in the
      neuromuscular economy (rectus femoris) in elderly.

PMID- 22453935
TI  - Three osteochondritis dissecans lesions in one knee: a case report.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) has been defined as a localized
      process in which a focus of subchondral bone and adjacent articular cartilage
      separates from the surrounding bone. With the knee being the most common location
      for OCD development and the propensity for this lesion to be found in those who
      participate in sports, a repetitive microtrauma hypothesis for its cause has
      gained favor. However, the cause of OCD remains controversial, as does the most
      appropriate treatment for the varying degrees of OCD lesions. CASE DESCRIPTION:
      We present a unique case of three OCD lesions in one knee. The patient was a
      young, athletic boy who developed three separate OCD lesions in his right knee
      over the course of 4 years. Temporally, the OCD lesions developed first in the
      lateral femoral condyle, then in the medial femoral condyle, and finally in the
      trochlea. LITERATURE REVIEW: Our literature review yielded a few reports of
      bicondylar OCD lesions. We identified no previous reports of three separate OCD
      lesions found in a single joint. PURPOSES AND CLINICAL RELEVANCE: This report
      illustrates how a uniquely affected knee with three OCD lesions was treated in
      three different ways with resolution of symptoms. Each of the OCD lesions was
      evaluated individually and treatment for each based on the severity of the lesion
      from the physical examination, imaging studies, and arthroscopic findings.

PMID- 22453936
TI  - The regulation of a cell's Ca(2+) signaling toolkit: the Ca (2+) homeostasome.
AB  - The Ca(2+) ion serves as a ubiquitous second messenger in eukaryotic cells and
      changes in the intracellular Ca(2+) concentration regulate many responses within
      a cell, but also communication between cells. In order to make use of such an
      apparently simple signal, i.e. a change in the intracellular Ca(2+)
      concentration, cells are equipped with sophisticated machinery to precisely
      regulate the shape (amplitude, duration) of Ca(2+) signals in a localization
      specific manner. To ascertain such a precise regulation, cells rely on the
      components of the Ca(2+) signaling toolkit. This embraces Ca(2+) entry systems
      including Ca(2+) channels in the plasma membrane and organellar membranes, and
      Ca(2+) extrusion/uptake systems including Ca(2+)-ATPases (Ca(2+) pumps) and
      Na(+)/Ca(2+) exchangers. Besides mitochondria, organelles implicated also in
      Ca(2+) signaling, cytosolic Ca(2+) buffers are cell-specific subtle modulators of
      Ca(2+) signals. The Ca(2+)-signaling components not only orchestrate their
      activity as to ascertain the high accuracy of intracellular Ca(2+) signaling, but
      they are also implicated in the regulation of their own expression. The total of
      the molecules that build the network of Ca(2+) signaling components, and that are
      involved in their own regulation as to maintain physiological Ca(2+) homeostasis
      resulting in phenotypic stability is named the Ca(2+) homeostasome. Mechanistic
      details on the functioning of the Ca(2+) homeostasome are presented.

PMID- 22453933
TI  - The interactions of oxidative stress and inflammation with vascular dysfunction
      in ageing: the vascular health triad.
AB  - Oxidative stress and inflammation are increased with advancing age. Evidence
      suggests that oxidative stress and inflammation both lead to impaired vascular
      function. There is also evidence to suggest that inflammation may cause an
      increase in radical production leading to enhanced oxidative stress. In addition,
      oxidative stress may cause an increase in inflammation; however, the interactions
      between these factors are not fully understood. In this review, we propose the
      vascular health triad, which draws associations and interactions between
      oxidative stress and inflammation seen in ageing, and the consequences for
      vascular function. We review evidence suggesting that exercise may ameliorate the
      age-related decline in vascular function, through reductions in both oxidative
      stress and inflammation.

PMID- 22453937
TI  - Methods to detect Ca(2+) in living cells.
AB  - Measurements of free cytosolic Ca(2+) concentration ([Ca(2+)](i)) or free Ca(2+)
      concentration in cellular organelles have become more routine. The primary reason
      for this is the availability of membrane permeant forms of Ca(2+) indicators that
      can easily enter cells. In this chapter, the properties required of an ideal
      Ca(2+) indicator are identified and the advantages and disadvantages of available
      Ca(2+) indicators are pointed out. The pitfalls associated with usage of Ca(2+)
      indicators together with the clear advantages of ratiometric over non-ratiometric
      indicators are discussed. The excitation of Ca(2+) indicators and detection of
      the emitted fluorescence light require dedicated equipment; epifluorescence or
      confocal microscopes are most frequently used for this purpose and the advantages
      and disadvantages of these are discussed. Calibration experiments are required to
      translate changes in the fluorescence of Ca(2+) indicators into real [Ca(2+)](i)
      changes, but this procedure is non-trivial and potential sources of error are
      identified. Future developments in the field of Ca(2+) detection are discussed.

PMID- 22453938
TI  - Development and optimization of FLIPR high throughput calcium assays for ion
      channels and GPCRs.
AB  - Ca(2+) permeable ion channels and GPCRs linked to Ca(2+) release are important
      drug targets, with modulation of Ca(2+) signaling increasingly recognized as a
      valid therapeutic strategy in a range of diseases. The FLIPR is a high throughput
      imaging plate reader that has contributed substantially to drug discovery efforts
      and pharmacological characterization of receptors and ion channels coupled to
      Ca(2+). Now in its fourth generation, the FLIPR(TETRA) is an industry standard
      for high throughput Ca(2+) assays. With an increasing number of excitation LED
      banks and emission filter sets available; FLIPR Ca(2+) assays are becoming more
      versatile. This chapter describes general methods for establishing robust FLIPR
      Ca(2+) assays, incorporating practical aspects as well as suggestions for assay
      optimization, to guide the reader in the development and optimization of high
      throughput FLIPR assays for ion channels and GPCRs.

PMID- 22453939
TI  - Two-photon calcium imaging in the intact brain.
AB  - The calcium ion is a fundamental second messenger that plays crucial roles in the
      pathophysiology of brain cells. In this chapter, we will focus on the measurement
      of calcium fluctuations as a reporter of cellular excitability of both neurons
      and glial cells in the intact central nervous system. We will first describe the
      methodological aspects of in vivo two-photon fluorescence calcium imaging and
      then review recent data highlighting the ways in which this technique is
      revolutionizing our understanding of brain circuits at the cellular level.
      Finally, we will discuss recent technical advancements that promise to open new
      horizons in the optical investigation of brain function in awake, behaving
      animals.

PMID- 22453940
TI  - Signaling through the extracellular calcium-sensing receptor (CaSR).
AB  - The extracellular calcium ([Formula: see text])-sensing receptor (CaSR) was the
      first GPCR identified whose principal physiological ligand is an ion, namely
      extracellular Ca(2+). It maintains the near constancy of [Formula: see text] that
      complex organisms require to ensure normal cellular function. A wealth of
      information has accumulated over the past two decades about the CaSR's structure
      and function, its role in diseases and CaSR-based therapeutics. This review
      briefly describes the CaSR and key features of its structure and function, then
      discusses the extracellular signals modulating its activity, provides an overview
      of the intracellular signaling pathways that it controls, and, finally, briefly
      describes CaSR signaling both in tissues participating in [Formula: see text]
      homeostasis as well as those that do not. Factors controlling CaSR signaling
      include various factors affecting the expression of the CaSR gene as well as
      modulation of its trafficking to and from the cell surface. The dimeric cell
      surface CaSR, in turn, links to various heterotrimeric and small molecular weight
      G proteins to regulate intracellular second messengers, lipid kinases, various
      protein kinases, and transcription factors that are part of the machinery
      enabling the receptor to modulate the functions of the wide variety of cells in
      which it is expressed. CaSR signaling is impacted by its interactions with
      several binding partners in addition to signaling elements per se (i.e., G
      proteins), including filamin-A and caveolin-1. These latter two proteins act as
      scaffolds that bind signaling components and other key cellular elements (e.g.,
      the cytoskeleton). Thus CaSR signaling likely does not take place randomly
      throughout the cell, but is compartmentalized and organized so as to facilitate
      the interaction of the receptor with its various signaling pathways.

PMID- 22453941
TI  - Ca(2+) signaling: an outlook on the characterization of Ca(2+) channels and their
      importance in cellular functions.
AB  - Calcium (Ca(2+)) is essential in regulating a plethora of cellular functions that
      includes cell proliferation and differentiation, axonal guidance and cell
      migration, neuro/enzyme secretion and exocytosis, development/maintenance of
      neural circuits, cell death and many more. Since Ca(2+) regulates so many
      fundamental processes, it could be anticipated that numerous Ca(2+) channels and
      transporters will assist in regulating Ca(2+) entry across the plasma membrane.
      Towards this several Ca(2+) channels such as voltage-gated channels, store
      operated Ca(2+) entry (SOCE) channels, NMDA, AMPA and other ligand gated channels
      have been identified. In recent years research focus has been targeted towards
      identification of the precise function of these essential channels. Furthermore,
      characterization of these individual Ca(2+) channels has also gained much
      attention, since specific Ca(2+) channels have been shown to influence a
      particular cellular response. Moreover, perturbations in these Ca(2+) channels
      have also been implicated in a spectrum of pathological conditions. Hence,
      understanding the precise involvement of these Ca(2+) channels in disease
      conditions would presumably unveil avenues for plausible therapeutic
      interventions. We thus review the role of Ca(2+) signaling in select -disease
      conditions and also provide experimental evidence as how they can be
      characterized in a given cell.

PMID- 22453942
TI  - Ryanodine receptor calcium release channels: an evolutionary perspective.
AB  - Ryanodine receptors (RyRs), along with the related inositol 1,4,5-trisphosphate
      receptors (IP(3)Rs), mediate the release of Ca(2+) from intracellular organelles
      of eukaryotes. As discussed in other chapters, such increases in intracellular
      Ca(2+) levels act a fundamental second messenger, regulating a diverse array of
      cellular processes. For over two decades, it has been reported that vertebrates
      express multiple RYR genes, whereas non-vertebrate multicellular organisms
      possess a single homologue within their genomes. Recently, the existence of RyR
      like channels in unicellular organisms has also been reported. This chapter
      exploits recent expansions in available genome data to generate an overview of
      the expression of RyR-like genes in organisms representing a broad range of
      viral, archaeal, bacterial and eukaryotic taxa. Analyses of the multidomain
      structures and phylogenetic relationships of these proteins has lead to a model
      in which, early during eukaryotic evolution, IP(3)R-like ancestral Ca(2+) release
      channels were converted to RyR proteins via the addition of promiscuous protein
      domains, possibly via horizontal gene transfer mechanisms.

PMID- 22453944
TI  - Ryanodine receptor physiology and its role in disease.
AB  - The ryanodine receptors (RyRs) is the major intracellular Ca(2+) release channel
      localized in the plasma membrane of the endoplasmatic/sarcoplasmatic reticulum.
      RyR-mediated Ca(2+) release is crucial for every heart beat and skeletal muscle
      contraction and also important in learning and memory. Given the important role
      RyR has in physiological functions it is not surprising that dysregulation and
      impaired RyR channel function contributes to severe pathologies e.g. cardiac
      arrhythmias and Alzheimer's disease. Mutations in the RyR channels are associated
      with a number of human disorders e.g. malignant hyperthermia (MH) and central
      core disease (CCD), catecholaminergic polymorphic ventricular tachycardia (CPVT),
      and arrhythmogenic right ventricular dysplasia (ARVD). RyRs are modulated
      directly and indirectly by various ions, small molecules and proteins and RyR
      structure and function are expected to be defined within this macromolecular set
      of interactions. This article discusses the physiological function of RyR and
      examines its role in disorders and diseases.

PMID- 22453943
TI  - Techniques and methodologies to study the ryanodine receptor at the molecular,
      subcellular and cellular level.
AB  - In excitable tissues, the ryanodine receptor Ca(2+) release channel (RyR) protein
      complex regulates excitation-contraction coupling, exocytosis, gene expression
      and apoptosis. Defects in RyR function, in genetic or acquired pathologies, lead
      to massive disruptions of Ca(2+) release that can be lethal. Therefore, RyR has
      emerged as a putative therapeutic target and an increasing number of RyR
      targeting drugs are currently being tested.Nonetheless this large-size channel is
      still a mystery in terms of structure, which hinders full characterization of the
      properties of this central protein. This chapter is dedicated to the methods
      available to examine RyR structure and function. The aim of the article is to
      concentrate on contemporary methodologies rather than focusing overtly on the
      progress that has been achieved using these techniques. Here we review a series
      of reliable approaches that are routinely employed to investigate this channel.
      Technical limitations are discussed, and technological developments are
      presented. This work is not a handbook, but it can be used as a resource and a
      starting point for the investigation of RyR at different levels of resolution.

PMID- 22453945
TI  - Phospholipase C.
AB  - Phospholipase C (PLC) family members constitute a family of diverse enzymes.
      Thirteen different family members have been cloned. These family members have
      unique structures that mediate diverse functions. Although PLC family members all
      appear to signal through the bi-products of cleaving phospholipids, it is clear
      that each family member, and at times each isoform, contributes to unique
      cellular functions. This chapter provides a review of the current literature. In
      addition, references have been provided for more in depth information regarding
      areas that are discussed. Ultimately, understanding the roles of the individual
      PLC enzymes, and their distinct cellular functions, will lead to a better
      understanding of the development of diseases and the maintenance of homeostasis.

PMID- 22453946
TI  - Inositol 1,4,5-trisphosphate and its receptors.
AB  - Activation of cells by many extracellular agonists leads to the production of
      inositol 1,4,5-trisphosphate (IP3). IP3 is a global messenger that easily
      diffuses in the cytosol. Its receptor (IP3R) is a Ca(2+)-release channel located
      on intracellular membranes, especially the endoplasmic reticulum (ER). The IP3R
      has an affinity for IP(3) in the low nanomolar range. A prime regulator of the
      IP3R is the Ca(2+) ion itself. Cytosolic Ca(2+) is considered as a co-agonist of
      the IP3R, as it strongly increases IP(3)R activity at concentrations up to about
      300 nM. In contrast, at higher concentrations, cytosolic Ca(2+) inhibits the
      IP3R. Also the luminal Ca(2+) sensitizes the IP3R. In higher organisms three
      genes encode for an IP3R and additional diversity exists as a result of
      alternative splicing mechanisms and the formation of homo- and heterotetramers.
      The various IP3R isoforms have a similar structure and a similar function, but
      due to differences in their affinity for IP3, their variable sensitivity to
      regulatory parameters, their differential interaction with associated proteins,
      and the variation in their subcellular localization, they participate differently
      in the formation of intracellular Ca(2+) signals and this affects therefore the
      physiological consequences of these signals.

PMID- 22453947
TI  - The discovery and structural investigation of the IP3 receptor and the associated
      IRBIT protein.
AB  - The IP3 receptor (IP3R) is a Ca(2+) channel that releases Ca(2+) from the
      endoplasmic reticulum (ER) and plays a variety of roles in cell functions. This
      receptor was discovered as a developmentally regulated glyco-phosphoprotein,
      known as P400, which was absent in cerebellar mutant mice. The IP3R has three
      different isoforms in vertebrates, and each IP3R is composed of different
      subdomains. The affinities of the IP3-binding core of the three isoforms of the
      IP3R for IP3 are similar. The N-terminal IP3-binding suppressor region of each
      isoform is responsible for its isoform-specific IP3-binding affinity. IP3 binding
      to the IP3-binding core leads to a conformational change, resulting in direct
      interactions of tyrosine-168 (in IP3R1)/tryptophane-168 (in IP3R2 and 3) in the N
      terminal suppressor region with the loop region of transmembrane 4-5. The
      suppressor region and C-terminal -portion which associate with nearly 20
      signaling molecules are located at the areas near the channel pore. The area
      including suppressor region and C-terminal portion are regarded as hot spots for
      the regulating opening and closing of the channel pore. A pseudo-ligand of the
      IP3R, known as IRBIT (IP3R binding protein released with inositol 1,4,5
      trisphosphate), that interacts with the IP3-binding core domain of the IP3R was
      discovered. IRBIT not only regulates Ca(2+) release by binding to the IP3-binding
      core domain but also regulates the acid-base balance by binding to various ion
      transporters, such as pancreas-type NBC1 (pNBC1) and CFTR. Most of the associated
      proteins bind to these areas and regulate IP3R channel gating. Cryo-electron
      microscopy shows a balloon-like structure, which has vacancy inside the IP3R with
      multi-porous surface area. The unique 3-dimensional structure of the IP3R is
      convenient for associating with many IP3R-associated proteins. Therefore, the
      IP3R serves as a signaling hub, which forms macromolecular complex with various
      molecules.

PMID- 22453948
TI  - Pyridine nucleotide metabolites and calcium release from intracellular stores.
AB  - Ca(2+) signals are probably the most common intracellular signaling elements,
      controlling an extensive range of responses in virtually all cells. Many cellular
      stimuli, often acting at cell surface receptors, evoke Ca(2+) signals by
      mobilizing Ca(2+) from intracellular stores. Inositol trisphosphate (IP3) was the
      first messenger shown to link events at the plasma membrane to release of Ca(2+)
      from the endoplasmic reticulum (ER), through activation of IP3-gated Ca(2+)
      release channels (IP3 receptors). Subsequently, two additional Ca(2+) mobilizing
      messengers were discovered, cADPR and NAADP. Both are metabolites of pyridine
      nucleotides, and may be produced by the same class of enzymes, ADP-ribosyl
      cyclases, such as CD38. Whilst cADPR mobilizes Ca(2+) from the ER by activation
      of ryanodine receptors (RyRs), NAADP releases Ca(2+) from acidic stores by a
      mechanism involving the activation of two pore channels (TPCs).

PMID- 22453949
TI  - NAADP on target.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent intracellular
      Ca(2+)-mobilising messenger. Much evidence indicates that NAADP targets novel
      Ca(2+) channels located on acidic organelles but the identity of these channels
      has remained obscure. Recent studies have converged on a novel class of ion
      channels, the two-pore channels (TPCs) as likely molecular targets. The location
      of these channels to the endo-lysosomal system and their sensitivity to NAADP
      match closely those of endogenous NAADP-sensitive channels in both mammalian
      cells and sea urchin eggs, where the effects of NAADP were discovered. Moreover,
      the functional coupling of TPCs to archetypal endoplasmic reticulum (ER) Ca(2+)
      channels is also matched. Biophysical analysis in conjunction with site-directed
      mutagenesis demonstrates that TPCs are pore-forming subunits of NAADP-gated ion
      channels. TPCs have a unique two-repeat structure, are regulated by N-linked
      glycosylation and harbor an endo-lysosomal targeting motif in their N-terminus.
      Knockdown studies have shown TPCs to regulate smooth muscle contraction,
      differentiation and endothelial cell activation consistent with previous studies
      implicating NAADP in these processes. Thus multiple lines of evidence indicate
      that TPCs are the likely long sought targets for NAADP.

PMID- 22453950
TI  - Store-operated Ca(2+) entry.
AB  - Store-operated Ca(2+) entry (SOCE) is an ubiquitous and major mechanism for
      Ca(2+) influx in mammalian cells with important physiological relevance. Since
      the discovery of SOCE in 1986 both, the mechanism that communicates the amount of
      Ca(2+) accumulated in the intracellular Ca(2+) stores to the plasma membrane
      channels and the nature of the capacitative channels, have been a matter of
      intense investigation. During the last decade, two of the major elements of SOCE,
      STIM1, the Ca(2+) sensor of the intracellular Ca(2+) compartments, and Orai1, the
      protein forming the channel that conducts the capacitative Ca(2+) release
      activated current I (CRAC), were identified. Together with these proteins,
      different homologues, including STIM2, Orai2 and Orai3, were identified, although
      their relevance in SOCE has not been fully characterized yet. Before the
      identification of STIM1 and Orai1, TRPC proteins were found to be involved in
      SOCE in different cell types, more likely conducting the non-selective
      capacitative current described as I (SOC). Current evidence indicates that STIM1,
      Orai1 and TRPC proteins dynamically interact forming a ternary complex that
      mediates SOCE in a number of cellular models. The dynamic interaction of STIM1
      with Orai1, TRPCs or both might provide an explanation to the distinct
      capacitative currents described in different cell types.

PMID- 22453951
TI  - Structure, regulation and biophysics of I(CRAC), STIM/Orai1.
AB  - Ca(2+) release activated Ca(2+) (CRAC) channels mediate robust Ca(2+) influx when
      the endoplasmic reticulum Ca(2+) stores are depleted. This essential process for
      T-cell activation as well as degranulation of mast cells involves the Ca(2+)
      sensor STIM1, located in the endoplasmic reticulum and the Ca(2+) selective Orai1
      channel in the plasma membrane. Our review describes the CRAC signaling pathway,
      the activation of which is initiated by a drop in the endoplasmic Ca(2+) level
      sensed by STIM1. This in term induces multimerisation and puncta-formation of
      STIM1 proteins is followed by their coupling to and activation of Orai channels.
      Consequently Ca(2+) entry is triggered through the Orai pore into the cytosol
      with subsequent closure of the channel by Ca(2+)-dependent inactivation. We will
      portray a mechanistic view of the events coupling STIM1 to Orai activation based
      on their structure and biophysics.

PMID- 22453952
TI  - Mitochondria-associated membranes (MAMs) as hotspot Ca(2+) signaling units.
AB  - The tight interplay between endoplasmic reticulum (ER) and mitochondria is a key
      determinant of cell function and survival through the control of intracellular
      calcium (Ca(2+)) signaling. The specific sites of physical association between ER
      and mitochondria are known as mitochondria-associated membranes (MAMs). It has
      recently become clear that MAMs are crucial for highly efficient transmission of
      Ca(2+) from the ER to mitochondria, thus controlling fundamental processes
      involved in energy production and also determining cell fate by triggering or
      preventing apoptosis. In this contribution, we summarize the main features of the
      Ca(2+)-signaling toolkit, covering also the latest breakthroughs in the field,
      such as the identification of novel candidate proteins implicated in
      mitochondrial Ca(2+) transport and the recent direct characterization of the high
      Ca(2+) microdomains between ER and mitochondria. We review the main functions of
      these two organelles, with special emphasis on Ca(2+) handling and on the
      structural and molecular foundations of the signaling contacts between them.
      Additionally, we provide important examples of the physiopathological role of
      this cross-talk, briefly describing the key role played by MAMs proteins in many
      diseases, and shedding light on the essential role of mitochondria-ER
      interactions in the maintenance of cellular homeostasis and the determination of
      cell fate.

PMID- 22453953
TI  - Calcium around the Golgi apparatus: implications for intracellular membrane
      trafficking.
AB  - As with other complex cellular functions, intracellular membrane transport
      involves the coordinated engagement of a series of organelles and machineries; in
      the last couple of decades more importance has been given to the role of calcium
      (Ca(2+)) in the regulation of membrane trafficking, which is directly involved in
      coordinating the endoplasmic reticulum-to-Golgi-to-plasma membrane delivery of
      cargo. Consequently, the Golgi apparatus (GA) is now considered not just the
      place proteins mature in as they move to their final destination(s), but it is
      increasingly viewed as an intracellular Ca(2+) store. In the last few years the
      mechanisms regulating the homeostasis of Ca(2+) in the GA and its role in
      membrane trafficking have begun to be elucidated. Here, these recent discoveries
      that shed light on the role Ca(2+) plays as of trigger of different steps during
      membrane trafficking has been reviewed. This includes recruitment of proteins and
      SNARE cofactors to the Golgi membranes, which are both fundamental for the
      membrane remodeling and the regulation of fusion/fission events occurring during
      the passage of cargo across the GA. I conclude by focusing attention on Ca(2+)
      homeostasis dysfunctions in the GA and their related pathological implications.

PMID- 22453954
TI  - Calcium binding proteins.
AB  - The role of Ca(2+) as a key and pivotal second messenger in cells depends largely
      on a wide number of heterogeneous so-called calcium binding proteins (CBP), which
      have the ability to bind this ion in specific domains. CBP contribute to the
      control of Ca(2+) concentration in the cytosol and participate in numerous
      cellular functions by acting as Ca(2+) transporters across cell membranes or as
      Ca(2+)-modulated sensors, i.e., decoding Ca(2+) signals. In this chapter we
      review the main Ca(2+)-modulated CBP, starting with those intracellular CBP that
      contain the structural EF-hand domain: parvalbumin, calmodulin, S100 proteins and
      calcineurin. Then, we address intracellular CBP lacking the EF-hand domain: CBP
      within intracellular Ca(2+) stores (paying special attention to calreticulin and
      calsequestrin), annexins and proteins that contain a C2 domain, such as protein
      kinase C (PKC) or sinaptotagmin. Finally, extracellular CBP have been classified
      in six groups, according to their Ca(2+) binding structures: (i) EF-hand domains;
      (ii) EGF-like domains; (iii) gamma-carboxyl glutamic acid (GLA)-rich domains;
      (iv) cadherin domains; (v) Ca(2+)-dependent (C)-type lectin-like domains; (vi)
      Ca(2+)-binding pockets of family C G-protein-coupled receptors. For all proteins,
      we briefly review their structure, location and function and additionally their
      potential as pharmacological targets in several human diseases.

PMID- 22453955
TI  - Cytoplasmic calcium buffering.
AB  - Calcium buffering is one of the mechanisms to control calcium (Ca(2+))
      persistence in the cytosol and hence, Ca(2+) dependence of many intracellular
      processes. Compared with Ca(2+) sequestration into intracellular Ca(2+) stores,
      Ca(2+) buffering is a rapid process occurring in sub-second scale.Ca(2+) buffers
      can be mobile or fixed depending of their molecular weight, but other parameters
      as their concentration, affinity for Ca(2+) or Ca(2+) binding and releasing
      kinetics are important to know their role in Ca(2+) signaling.This process
      determines Ca(2+) diffusion and spatiotemporal Ca(2+) signaling in the cell and
      is one of the basis of the versatility and complexity of Ca(2+) as intracellular
      messenger.

PMID- 22453956
TI  - Elementary calcium release events from the sarcoplasmic reticulum in the heart.
AB  - Ca(2+) release events underlie global Ca(2+) signaling yet they are regulated by
      local, subcellular signaling features. Here we review the latest developments of
      different elementary Ca(2+) release features that include Ca(2+) sparks, Ca(2+)
      blinks (the corresponding depletion of Ca(2+) in the sarcoplasmic reticulum (SR)
      during a spark) and the recently identified small Ca(2+) release events called
      quarky SR Ca(2+) release (QCR). QCR events arise from the opening of only a few
      type 2 ryanodine receptors (RyR2s) - possibly only one. Recent reports suggest
      that QCR events can be commingled with Ca(2+) sparks and may thus explain some
      variations observed in Ca(2+) sparks. The Ca(2+) spark termination mechanism and
      the number of RyR2 channels activated during a Ca(2+) spark will be discussed
      with respect to both Ca(2+) sparks and QCR events.

PMID- 22453957
TI  - Calcium oscillations and pacemaking.
AB  - Calcium plays important role in biological systems where it is involved in
      diverse mechanisms such as signaling, muscle contraction and neuromodulation.
      Action potentials are generated by dynamic interaction of ionic channels located
      on the plasma-membrane and these drive the rhythmic activity of biological
      systems such as the smooth muscle and the heart. However, ionic channels are not
      the only pacemakers; an intimate interaction between intracellular Ca(2+) stores
      and ionic channels underlie rhythmic activity. In this review we will focus on
      the role of Ca(2+) stores in regulation of rhythmical behavior.

PMID- 22453958
TI  - Calcium oscillations and waves in cells.
AB  - From beginning of the life to final moment of the life, Ca(2+) functions as an
      important signaling messenger. The intracellular Ca(2+) concentration,
      [Ca(2+)](i), in resting cells is normally maintained at around 100 nM with a very
      steep ~20,000 times concentration gradient of Ca(2+) between extracellular and
      intracellular compartments. Ca(2+) signals in the form of time-dependent changes
      in [Ca(2+)](i) appear as brief spikes that are organized into regenerative Ca(2+)
      waves. The release of Ca(2+) from internal stores plays a key role in regulating
      such Ca(2+) signals. Since global Ca(2+) oscillations arise from Ca(2+) waves
      initiated locally, it results in generation of stochastic Ca(2+) oscillations. In
      addition, the hierarchical organization of signaling structures translate the
      molecular fluctuations of single channels to the whole cell leading to formation
      of stochastic media. Several recent observations indicate that [Ca(2+)](i)
      changes are fluctuation driven as opposed to a typical deterministic
      intracellular reaction-diffusion system model. Elucidation of this signaling
      mechanism can provide detailed knowledge of relationship between cell signaling
      and cell physiology of living systems.

PMID- 22453959
TI  - Calcium signaling: from single channels to pathways.
AB  - Ca(2+) is not only one of the most versatile and ubiquitous second messengers but
      also a well-established representative example of cell signaling. The
      identification of most key elements involved in Ca(2+) signaling enables a
      mechanistic and quantitative understanding of this particular pathway. Cellular
      behavior relies in general on the orchestration of molecular behavior leading to
      reliable cellular responses that allow for regulation and adaptation. Ca(2+)
      signaling uses a hierarchical organization to transform single molecule behavior
      into cell wide signals. We have recently shown experimentally that this
      organization carries single channel signatures onto the whole cell level and
      renders Ca(2+) oscillations stochastic. Here, we briefly review the co-evolution
      of experimental and theoretical studies in Ca(2+) -signaling and show how dynamic
      bottom-up modeling can be used to address -biological questions and illuminate
      biological principles of cell signaling.

PMID- 22453960
TI  - Simulation strategies for calcium microdomains and calcium-regulated calcium
      channels.
AB  - In this article, we present an overview of simulation strategies in the context
      of subcellular domains where calcium-dependent signaling plays an important role.
      The presentation follows the spatial and temporal scales involved and represented
      by each algorithm. As an exemplary cell type, we will mainly cite work done on
      striated muscle cells, i.e. skeletal and cardiac muscle. For these cells, a
      wealth of ultrastructural, biophysical and electrophysiological data is at hand.
      Moreover, these cells also express ubiquitous signaling pathways as they are
      found in many other cell types and thus, the generalization of the methods and
      results presented here is straightforward.The models considered comprise the
      basic calcium signaling machinery as found in most excitable cell types including
      Ca(2+) ions, diffusible and stationary buffer systems, and calcium regulated
      calcium release channels. Simulation strategies can be differentiated in
      stochastic and deterministic algorithms. Historically, deterministic approaches
      based on the macroscopic reaction rate equations were the first models
      considered. As experimental methods elucidated highly localized Ca(2+) signaling
      events occurring in femtoliter volumes, stochastic methods were increasingly
      considered. However, detailed simulations of single molecule trajectories are
      rarely performed as the computational cost implied is too large. On the
      mesoscopic level, Gillespie's algorithm is extensively used in the systems
      biology community and with increasing frequency also in models of microdomain
      calcium signaling. To increase computational speed, fast approximations were
      derived from Gillespie's exact algorithm, most notably the chemical Langevin
      equation and the tau-leap algorithm. Finally, in order to integrate deterministic
      and stochastic effects in multiscale simulations, hybrid algorithms are
      increasingly used. These include stochastic models of ion channels combined with
      deterministic descriptions of the calcium buffering and diffusion system on the
      one hand, and algorithms that switch between deterministic and stochastic
      simulation steps in a context-dependent manner on the other. The basic
      assumptions of the listed methods as well as implementation schemes are given in
      the text. We conclude with a perspective on possible future developments of the
      field.

PMID- 22453961
TI  - Combined computational and experimental approaches to understanding the Ca(2+)
      regulatory network in neurons.
AB  - Ca(2+) is a ubiquitous signaling ion that regulates a variety of neuronal
      functions by binding to and altering the state of effector proteins. Spatial
      relationships and temporal dynamics of Ca(2+) elevations determine many cellular
      responses of neurons to chemical and electrical stimulation. There is a wealth of
      information regarding the properties and distribution of Ca(2+) channels, pumps,
      exchangers, and buffers that participate in Ca(2+) regulation. At the same time,
      new imaging techniques permit characterization of evoked Ca(2+) signals with
      increasing spatial and temporal resolution. However, understanding the
      mechanistic link between functional properties of Ca(2+) handling proteins and
      the stimulus-evoked Ca(2+) signals they orchestrate requires consideration of the
      way Ca(2+) handling mechanisms operate together as a system in native cells. A
      wide array of biophysical modeling approaches is available for studying this
      problem and can be used in a variety of ways. Models can be useful to explain the
      behavior of complex systems, to evaluate the role of individual Ca(2+) handling
      mechanisms, to extract valuable parameters, and to generate predictions that can
      be validated experimentally. In this review, we discuss recent advances in
      understanding the underlying mechanisms of Ca(2+) signaling in neurons via
      mathematical modeling. We emphasize the value of developing realistic models
      based on experimentally validated descriptions of Ca(2+) transport and buffering
      that can be tested and refined through new experiments to develop increasingly
      accurate biophysical descriptions of Ca(2+) signaling in neurons.

PMID- 22453963
TI  - The biology of protein kinase C.
AB  - This review gives a basic introduction to the biology of protein kinase C, one of
      the first calcium-dependent kinases to be discovered. We review the structure and
      function of protein kinase C, along with some of the substrates of individual
      isoforms. We then review strategies for inhibiting PKC in experimental systems
      and finally discuss the therapeutic potential of targeting PKC. Each aspect is
      covered in summary, with links to detailed resources where appropriate.

PMID- 22453964
TI  - The role of C2 domains in PKC signaling.
AB  - More than two decades ago, the discovery of the first C2 domain in conventional
      Protein Kinase Cs (cPKCs) and of its role as a calcium-binding motif began to
      shed light on the activation mechanism of this family of Serine/Threonine kinases
      which are involved in several critical signal transduction pathways. In this
      chapter, we review the current knowledge of the structure and the function of the
      different C2 domains in PKCs. The C2 domain of cPKCs is a calcium sensor and its
      calcium-dependent binding to phospholipids is crucial for kinase activation.
      While the functional role of the cPKC C2 domain is better understood,
      phylogenetic analysis revealed that the novel C2 domain is more ancient and
      related to the C2 domain in the fungal PKC family, while the cPKC C2 domain is
      first associated with PKC in metazoans. The C2 domain of novel PKCs (nPKCs) does
      not contain a calcium-binding motif but still plays a critical role in nPKCs
      activation by regulating C1-C2 domain interactions and consequently C2 domain
      mediated inhibition in both the nPKCs of the epsilon family and the nPKCs of the
      delta family. Moreover, the C2 domain of the nPKCs of the delta family was shown
      to recognize phosphotyrosines in a novel mode different from the ones observed
      for the Src Homology 2 (SH2) and the phosphotyrosine binding domains (PTB). By
      binding to phosphotyrosines, the C2 domain regulates the activation of this
      subclass of PKCs. The C2 domain was also shown to be involved in protein-protein
      interactions and binding to the receptor for activated C-kinase (RACKs) thus
      contributing to the subcellular localization of PKCs. In summary, the C2 domain
      is a critical player that can sense the activated signaling pathway in response
      to external stimuli to specifically regulate the different conventional and novel
      PKC isoforms.

PMID- 22453965
TI  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the heart.
AB  - Aim of this review is to give an overview and discuss recent findings on the role
      of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the heart. Special
      attention is drawn to excitation-contraction coupling (ECC) and excitation
      transcription coupling (ETC). Because CaMKII expression and activity are
      increased in cardiac hypertrophy, heart failure, and during arrhythmias both in
      animal models as well as in the human heart a clinical significance of CaMKII is
      implied.

PMID- 22453966
TI  - The role of molecular regulation and targeting in regulating calcium/calmodulin
      stimulated protein kinases.
AB  - Calcium/calmodulin-stimulated protein kinases can be classified as one of two
      types - restricted or multifunctional. This family of kinases contains several
      structural similarities: all possess a calmodulin binding motif and an
      autoinhibitory region. In addition, all of the calcium/calmodulin-stimulated
      protein kinases examined in this chapter are regulated by phosphorylation, which
      either activates or inhibits their kinase activity. However, as the
      multifunctional calcium/calmodulin-stimulated protein kinases are ubiquitously
      expressed, yet regulate a broad range of cellular functions, additional levels of
      regulation that control these cell-specific functions must exist. These
      additional layers of control include gene expression, signaling pathways, and
      expression of binding proteins and molecular targeting. All of the
      multifunctional calcium/calmodulin-stimulated protein kinases examined in this
      chapter appear to be regulated by these additional layers of control, however,
      this does not appear to be the case for the restricted kinases.

PMID- 22453967
TI  - Calcium sensing in exocytosis.
AB  - Neurotransmitters, neuropeptides and hormones are released through regulated
      exocytosis of synaptic vesicles and large dense core vesicles. This complex and
      highly regulated process is orchestrated by SNAREs and their associated proteins.
      The triggering signal for regulated exocytosis is usually an increase in
      intracellular calcium levels. Besides the triggering role, calcium signaling
      modulates the precise amount and kinetics of vesicle release. Thus, it is a
      central question to understand the molecular machineries responsible for calcium
      sensing in exocytosis. Here we provide an overview of our current understanding
      of calcium sensing in neurotransmitter release and hormone secretion.

PMID- 22453968
TI  - Regulation of voltage-gated calcium channels by synaptic proteins.
AB  - Calcium entry through neuronal voltage-gated calcium channels into presynaptic
      nerve terminal is a key step in synaptic exocytosis. In order to receive the
      calcium signal and trigger fast, efficient and spatially delimited
      neurotransmitter release, the vesicle-docking/release machinery must be located
      near the calcium source. In many cases, this close localization is achieved by a
      direct interaction of several members of the vesicle release machinery with the
      calcium channels. In turn, the binding of synaptic proteins to presynaptic
      calcium channels modulates channel activity to provide fine control over calcium
      entry, and thus modulates synaptic strength. In this chapter we summarize our
      present knowledge of the molecular mechanisms by which synaptic proteins regulate
      presynaptic calcium channel activity.

PMID- 22453962
TI  - alpha7 nicotinic ACh receptors as a ligand-gated source of Ca(2+) ions: the
      search for a Ca(2+) optimum.
AB  - The spatiotemporal distribution of cytosolic Ca(2+) ions is a key determinant of
      neuronal behavior and survival. Distinct sources of Ca(2+) ions including ligand-
      and voltage-gated Ca(2+) channels contribute to intracellular Ca(2+) homeostasis.
      Many normal physiological and therapeutic neuronal functions are Ca(2+)
      dependent, however an excess of cytosolic Ca(2+) or a lack of the appropriate
      balance between Ca(2+) entry and clearance may destroy cellular integrity and
      cause cellular death. Therefore, the existence of optimal spatiotemporal patterns
      of cytosolic Ca(2+) elevations and thus, optimal activation of ligand- and
      voltage-gated Ca(2+) ion channels are postulated to benefit neuronal function and
      survival. Alpha7 nicotinic -acetylcholine receptors (nAChRs) are highly permeable
      to Ca(2+) ions and play an important role in modulation of neurotransmitter
      release, gene expression and neuroprotection in a variety of neuronal and non
      neuronal cells. In this review, the focus is placed on alpha7 nAChR-mediated
      currents and Ca(2+) influx and how this source of Ca(2+) entry compares to NMDA
      receptors in supporting cytosolic Ca(2+) homeostasis, neuronal function and
      survival.

PMID- 22453969
TI  - Regulation of intercellular calcium signaling through calcium interactions with
      connexin-based channels.
AB  - The synchronization of numerous cellular events requires complex electric and
      metabolic cell-cell interactions. Connexins are a family of membrane proteins
      that constitute the molecular basis of two kinds of channels: gap junction
      channels (GJCs), which allow direct cytoplasm-cytoplasm communication, and
      hemichannels (HCs) that provide a pathway for exchanges between the intra and
      extra-cellular milieu. Both kind of connexin-based channels support intercellular
      communication via intercellular propagation of calcium waves. Here, we review
      evidence supporting the role of Ca(2+) in the regulation of GJCs and HCs formed
      by connexins. Also it is speculated how these connexin-based channels could
      contribute to the propagation of intercellular Ca(2+) signals.

PMID- 22453970
TI  - Calcium signaling in vascular smooth muscle cells: from physiology to pathology.
AB  - Cyclic variations in calcium (Ca(2+)) concentrations, through a process called
      excitation-contraction coupling, allow regulation of vascular smooth muscle cells
      contractility and thus modulation of vascular tone and blood pressure. As a
      second messenger, Ca(2+) also activates signaling cascades leading to
      transcription factors activation in a process called excitation-transcription
      coupling. Furthermore, recent evidences indicate an interaction between post
      transcriptional regulation by microRNAs (miRNAs) and Ca(2+) signaling. All these
      actors, which are frequently altered in vascular diseases, will be reviewed here.

PMID- 22453971
TI  - Calcium and endothelium-mediated vasodilator signaling.
AB  - Vascular tone refers to the balance between arterial constrictor and dilator
      activity. The mechanisms that underlie tone are critical for the control of
      haemodynamics and matching circulatory needs with metabolism, and thus
      alterations in tone are a primary factor for vascular disease etiology. The
      dynamic spatiotemporal control of intracellular Ca(2+) levels in arterial
      endothelial and smooth muscle cells facilitates the modulation of multiple
      vascular signaling pathways. Thus, control of Ca(2+) levels in these cells is
      integral for the maintenance of tone and blood flow, and intimately associated
      with both physiological and pathophysiological states. Hence, understanding the
      mechanisms that underlie the modulation of vascular Ca(2+) activity is critical
      for both fundamental knowledge of artery function, and for the development of
      targeted therapies. This brief review highlights the role of Ca(2+) signaling in
      vascular endothelial function, with a focus on contact-mediated vasodilator
      mechanisms associated with endothelium-derived hyperpolarization and the
      longitudinal conduction of responses over distance.

PMID- 22453972
TI  - Calcium signaling in cerebral vasoregulation.
AB  - The tight coupling of regional neurometabolic activity with synaptic activity and
      regional cerebral blood perfusion constitutes a single functional unit, described
      generally as a neurovascular unit. This is central to any discussion of
      haemodynamic response linked to any neuronal activation. In normal as well as in
      pathologic conditions, neurons, astrocytes and endothelial cells of the
      vasculature interact to generate the complex activity-induced cerebral
      haemodynamic responses, with astrocytes not only partaking in the signaling but
      actually controlling it in many cases. Neurons and astrocytes have highly
      integrated signaling mechanisms, yet they form two separate networks.
      Bidirectional neuron-astrocyte interactions are crucial for the function and
      survival of the central nervous system. The primary purpose of such regulation is
      the homeostasis of the brain's microenvironment. In the maintenance of such
      homeostasis, astrocytic calcium response is a crucial variable in determining
      neurovascular control. Future work will be directed towards resolving the nature
      and extent of astrocytic calcium-mediated mechanisms for gene transcription, in
      modelling neurovascular control, and in determining calcium sensitive imaging
      assays that can capture disease variables.

PMID- 22453973
TI  - Ca(2+) signaling mechanisms in bovine adrenal chromaffin cells.
AB  - Calcium (Ca(2+)) is a crucial intracellular messenger in physiological aspects of
      cell signaling. Adrenal chromaffin cells are the secretory cells from the adrenal
      gland medulla that secrete catecholamines, which include epinephrine and
      norepinephrine important in the 'fight or flight' response. Bovine adrenal
      chromaffin cells have long been used as an important model for secretion 
      (exocytosis) not only due to their importance in the short-term stress response,
      but also as a neuroendocrine model of neurotransmtter release, as they have all
      the same exocytotic proteins as neurons but are easier to prepare, culture and
      use in functional assays. The components of the Ca(2+) signal transduction
      cascade and it role in secretion has been extensively characterized in bovine
      adrenal chromaffin cells. The Ca(2+) sources, signaling molecules and how this
      relates to the short-term stress response are reviewed in this book chapter in an
      endeavor to generally -overview these mechanisms in a concise and uncomplicated
      manner.

PMID- 22453974
TI  - Calcium stores in vertebrate photoreceptors.
AB  - This review lays out the emerging evidence for the fundamental role of Ca(2+)
      stores and store-operated channels in the Ca(2+) homeostasis of rods and cones.
      Calcium-induced calcium release (CICR) is a major contributor to steady-state and
      light-evoked photoreceptor Ca(2+) homeostasis in the darkness whereas store
      operated Ca(2+) channels play a more significant role under sustained
      illumination conditions. The homeostatic response includes dynamic interactions
      between the plasma membrane, endoplasmic reticulum (ER), mitochondria and/or
      outer segment disk organelles which dynamically sequester, accumulate and release
      Ca(2+). Coordinated activation of SERCA transporters, ryanodine receptors (RyR),
      inositol triphosphate receptors (IP3Rs) and TRPC channels amplifies cytosolic
      voltage-operated signals but also provides a memory trace of previous exposures
      to light. Store-operated channels, activated by the STIM1 sensor, prevent
      pathological decrease in [Ca(2+)]i mediated by excessive activation of PMCA
      transporters in saturating light. CICR and SOCE may also modulate the
      transmission of afferent and efferent signals in the outer retina. Thus, Ca(2+)
      stores provide additional complexity, adaptability, tuneability and speed to
      photoreceptor signaling.

PMID- 22453975
TI  - Stem cells and calcium signaling.
AB  - The increasing interest in stem cell research is linked to the promise of
      developing treatments for many lifethreatening, debilitating diseases, and for
      cell replacement therapies. However, performing these therapeutic innovations
      with safety will only be possible when an accurate knowledge about the molecular
      signals that promote the desired cell fate is reached. Among these signals are
      transient changes in intracellular Ca(2+) concentration [Ca(2+)](i). Acting as an
      intracellular messenger, Ca(2+) has a key role in cell signaling pathways in
      various differentiation stages of stem cells. The aim of this chapter is to
      present a broad overview of various moments in which Ca(2+)-mediated signaling is
      essential for the maintenance of stem cells and for promoting their development
      and differentiation, also focusing on their therapeutic potential.

PMID- 22453976
TI  - Calcium signaling in osteoclast differentiation and bone resorption.
AB  - Calcium (Ca(2+)) signaling controls multiple cellular functions and is regulated
      by the release of Ca(2+) from internal stores and its entry from the
      extracellular fluid. Ca(2+) signals in osteoclasts are essential for diverse
      cellular functions including differentiation, bone resorption and gene
      transcription. Recent studies have highlighted the importance of intracellular
      Ca(2+) signaling for osteoclast differentiation. Receptor activator of NF-kappaB
      ligand (RANKL) signaling induces oscillatory changes in intracellular Ca(2+)
      concentrations, resulting in Ca(2+)/calcineurin-dependent dephosphorylation and
      activation of nuclear factor of activated T cells c1 (NFATc1), which translocates
      to the nucleus and induces osteoclast-specific gene transcription to allow
      differentiation of osteoclasts. Recently, some reports indicated that RANKL
      induced Ca(2+) oscillation involved not only repetitive intracellular Ca(2+)
      release from inositol 1, 4, 5-triphosphate channels in Ca(2+) store sites, but
      also via store-operated Ca(2+) entry and Ca(2+) entry via transient receptor
      potential V channels during osteoclast differentiation. Ca(2+)-regulatory
      cytokines and elevation of extracellular Ca(2+) concentrations have been shown to
      increase intracellular Ca(2+) concentrations ([Ca(2+)](i)) in mature osteoclasts,
      regulating diverse cellular functions. RANKL-induced [Ca(2+)](i) increase has
      been reported to inhibit cell motility and the resorption of cytoskeletal
      structures in mature osteoclasts, resulting in suppression of bone-resorption
      activity. In conclusion, Ca(2+) signaling activates differentiation in osteoclast
      precursors but suppresses resorption in mature osteoclasts. This chapter focuses
      on the roles of long-term Ca(2+) oscillations in differentiation and of short
      term Ca(2+) increase in osteoclastic bone resorption activity.

PMID- 22453977
TI  - Calcium signaling in renal tubular cells.
AB  - The kidney handles calcium by filtration and reabsorption. About 60% of the
      plasma calcium is filterable, and 99% is reabsorbed in the tubule. In the
      proximal tubule, the reabsorption is passive and paracellular, but in the distal
      tubule is active and transcellular. Thus, renal tubular cells are exposed to very
      high concentrations of calcium in both, the extracellular and the intracellular
      compartments. Extracellular calcium signaling is transmitted by the calcium
      sensing receptor, located both in the luminal and basolateral sides of tubular
      cells. This receptor is able to control levels of extracellular calcium and acts
      in consequence to maintain calcium homeostasis. Furthermore, renal tubular cells
      possess several calcium channels that regulate some of the cell functions. Among
      those, voltage gated calcium channels, transient receptor potential channels and
      N-methyl-D-aspartate receptor channels have been reported to control several
      functions. Those functions include survival, apoptosis, differentiation,
      epithelial-mesenchymal transition, and active vitamin D and renin synthesis.

PMID- 22453978
TI  - Calcium in epidermis.

PMID- 22453979
TI  - Calcium signaling in mast cells: focusing on L-type calcium channels.
AB  - Mast cells play central roles in adaptive and innate immunity. IgE-dependent
      stimulation of the high-affinity IgE receptor (FcepsilonRI) results in rapid
      secretion of various proinflammatory chemical mediators and cytokines. All of the
      outputs depend to certain degrees on an increase in the intracellular Ca(2+)
      concentration, and influx of Ca(2+) from the extracellular space is often
      required for their full activation. There is strong evidence that FcepsilonRI
      stimulation induces two different modes of Ca(2+) influx, store-operated Ca(2+)
      entry (SOCE) and non-SOCE, which are activated in response to endoplasmic
      reticulum Ca(2+) store depletion and independently of Ca(2+) store depletion,
      respectively, in mast cells. Although Ca(2+) release-activated Ca(2+) channels
      are the major route of SOCE, recent evidence indicates that they are not the only
      Ca(2+) channels activated by Ca(2+) store depletion. The recent data suggest that
      L-type Ca(2+) channels, which were thought to be a characteristic feature of
      excitable cells, exist in mast cells to mediate non-SOCE, which is critical for
      protecting mast cells against activation-induced mitochondrial cell death. In
      this chapter, we provide an overview of recent advances in our understanding of
      Ca(2+) signaling in mast cells with a special attention to the emerging role for
      the L-type Ca(2+) channels as a regulator of mast cell survival.

PMID- 22453980
TI  - Proteinase-activated receptors (PARs) and calcium signaling in cancer.
AB  - Proteinase activated receptors (PARs), a small subfamily of G protein-coupled
      receptors with four members, PAR1, PAR2, PAR3 and PAR4, are expressed in various
      tumours from epithelial origin and can play an important role in tumour
      progression and metastasis. Within the complex intracellular PAR signaling
      networks triggered by PARs, an elevation in intracellular free calcium ion
      concentrations represents a key second messenger system. In this review, we
      summarize current information about the mechanisms whereby PARs can signal via
      intracellular calcium in the setting of cancer and we discuss possibilities for
      using the PAR-[Ca(2+)](i) signaling pathway as a target for the therapy of
      epithelial cancer.

PMID- 22453981
TI  - Mechanosensory calcium signaling.
AB  - Mechanotransduction describes the cellular process by which mechanical stimuli
      are translated into intracellular adaptive responses through biochemical signals.
      Current research has begun to focus on the once-forgotten organelle, the primary
      cilia, in this mechanotransduction process. Primary cilia are found on almost
      every cell type, with a functional role in transducing mechanical and
      extracellular signals towards intracellular responses through the ciliary
      extension into the extracellular space. In this regard, the modulation of
      intracellular calcium signaling by various mechanical stimuli has generated an
      assortment of attractive models to understand this mechanotransduction process.

PMID- 22453982
TI  - Role Ca(2+) in mechanisms of the red blood cells microrheological changes.
AB  - To assess the physiological role of intracellular Ca(2+) in the changes of
      microrheological red blood cell (RBC) properties (RBC deformability and
      aggregation), we employed several types of chemicals that can increase and
      decrease of the intracellular Ca(2+) concentration. The rise of Ca(2+) influx,
      stimulated by mechanical loading, A23187, thrombin, prostaglandin F(2alpha) was
      accompanied by a moderate red cell deformability lowering and an increase of
      their aggregation. In contrast, Ca(2+) entry blocking into the red cells by
      verapamil led to a significant RBC aggregation decrease and deformability rise.
      Similar microrheological changes were observed in the red blood cells treated
      with phosphodiesterase inhibitors IBMX, vinpocetine, rolipram, pentoxifylline.
      When forskolin (10 MUM), an AC stimulator was added to RBC suspension, the RBC
      deformability was increased (p <0.05). Somewhat more significant deformability
      rise appeared after RBC incubation with dB-AMP. Red cell aggregation was
      significantly decreased under these conditions (p<0.01). On the whole the total
      data clearly show that the red cell aggregation and deformation changes were
      connected with an activation of both intracellular signaling pathways: Ca(2+)
      regulatory mechanism and Gs-protein/adenylyl-cyclase-cAMP system. And the final
      red cell microrheological regulatory effect is connected with the crosstalk
      between these systems.

PMID- 22453983
TI  - Calcium imaging in the zebrafish.
AB  - The zebrafish (Danio rerio) has emerged as a new model system during the last
      three decades. The fact that the zebrafish larva is transparent enables
      sophisticated in vivo imaging. While being the vertebrate, the reduced complexity
      of its nervous system and small size make it possible to follow large-scale
      activity in the whole brain. Its genome is sequenced and many genetic and
      molecular tools have been developed that simplify the study of gene function.
      Since the mid 1990s, the embryonic development and neuronal function of the
      larval, and later, adult zebrafish have been studied using calcium imaging
      methods. The choice of calcium indicator depends on the desired number of cells
      to study and cell accessibility. Dextran indicators have been used to label cells
      in the developing embryo from dye injection into the one-cell stage. Dextrans
      have also been useful for retrograde labeling of spinal cord neurons and cells in
      the olfactory system. Acetoxymethyl (AM) esters permit labeling of larger areas
      of tissue such as the tectum, a region responsible for visual processing.
      Genetically encoded calcium indicators have been expressed in various tissues by
      the use of cell-specific promoters. These studies have contributed greatly to our
      understanding of basic biological principles during development and adulthood,
      and of the function of disease-related genes in a vertebrate system.

PMID- 22453984
TI  - Calcium signaling in Xenopus oocyte.
AB  - Knowledge about calcium signaling had increased thanks to the development and
      manipulation of various cell models. Among all of these prototypes, Xenopus
      laevis oocyte appears to be one of the most relevant. The understanding of the
      role of calcium during oocyte oogenesis, maturation and fertilization is
      facilitated by the big size of the cell but also by using imaging and
      electrophysiological approaches. So, this chapter presents how recordings of
      calcium-activated chloride channels and Store-Operated Calcium Channels
      activities lead to demonstrate the implication of the MPF in the uncoupling
      between intracellular calcium releasing and capacitative calcium entry. Moreover,
      it will help us to understand the several reorganizations happening consequently
      to the pH variations of maturation or just at the moment of fertilization.

PMID- 22453985
TI  - Calcium oscillations, oocyte activation, and phospholipase C zeta.
AB  - In mammals, gamete fusion initiates a succession of oscillations in the
      intracellular concentration of calcium within the oocyte, prompting a series of
      events to occur that are collectively known as "oocyte activation". Such events
      are a fundamental necessity for the initiation of cell division and subsequent
      embryogenesis. Compelling evidence now indicates that these calcium oscillations
      are caused by a testis-specific phospholipase C (PLC) termed PLCzeta (PLCzeta),
      released into the oocyte following gamete fusion. A series of recent studies
      indicate that abnormal expression or aberrant activity of PLCzeta is linked to
      certain types of human male infertility, where oocyte activation ability is
      impaired or absent altogether. In this chapter, we discuss the critical role of
      calcium oscillations in the process of oocyte activation, review the role of PLCs
      in this fundamental biological reaction, describe how PLCzeta has been formally
      linked to male infertility, and postulate the potential roles for PLCzeta in
      terms of clinical diagnosis and therapy.

PMID- 22453986
TI  - Nuclear calcium signaling and its involvement in transcriptional regulation in
      plants.
AB  - Calcium is a key second messenger in signaling pathways associated with
      developmental and adaptive processes in plants. Stimulus-specific calcium
      signals, considered as calcium signatures, are translated into appropriate
      cellular responses through the action of various calcium-binding proteins and
      downstream effectors. We review here recent progress made in calcium signaling in
      the nucleus of plant cell. Experimental evidences show that nuclei can generate
      calcium signals on their own and point out the importance of calcium in the
      regulation of gene transcription. Future directions are given concerning the need
      to elucidate the mechanisms involved in the regulation of nuclear calcium
      homeostasis, the conversion of calcium signals into transcriptional responses or
      other fundamental downstream nuclear functions. Overall, a better understanding
      of nuclear signaling will be useful to get an integrated picture of the signaling
      network of the plant cell.

PMID- 22453988
TI  - Proarrhythmic atrial calcium cycling in the diseased heart.
AB  - During the last decades Ca(2+) has been found to play a crucial role in cardiac
      arrhythmias associated with heart failure and a number of congenital arrhythmia
      syndromes. Recent studies demonstrated that altered atrial Ca(2+) cycling may
      promote the initiation and maintenance of atrial fibrillation, the most common
      clinical arrhythmia that contributes significantly to population morbidity and
      mortality. This article describes physiological Ca(2+) cycling mechanisms in
      atrial cardiomyocytes and relates them to fundamental cellular proarrhythmic
      mechanisms involving Ca(2+) signaling abnormalities in the atrium during atrial
      fibrillation.

PMID- 22453989
TI  - Neuronal calcium signaling and Alzheimer's disease.
AB  - Calcium plays a major role in normal functioning of the cells. Deregulation of
      calcium-mediated signaling has been implicated in many neurodegenerative diseases
      including Alzheimer's disease. Studies in neurons and mice expressing Alzheimer's
      disease-associated transgenes have shown that the expression of familial
      Alzheimer's disease (FAD) mutants of presenilin (PS) and amyloid precursor
      protein (APP) alter calcium homeostasis and cause synaptic dysfunction and
      dendritic spine loss in neurons. Mechanistic studies have shown that FAD mutants
      of presenilin can affect the intracellular calcium levels by affecting the ER
      calcium stores. A function for presenilins as ER calcium leak channels has been
      established and studies show that presenilins affect ER calcium load through an
      effect on IP(3) receptors, ryanodine receptors, or SERCA pumps. Even in the
      absence of an active gamma-secretase complex, presenilins seem to affect calcium
      homeostasis suggesting that these two functions of presenilins are independent of
      each other. Studies using FAD mutants of APP have shown that unlike presenilins,
      FAD-APP do not affect calcium homeostasis in the absence of Abeta. Both Abeta and
      presenilins seem to affect calcium homeostasis at very early stages of disease
      development affecting the synaptic transmission and function prior to neuritic
      plaque development. Altered calcium signaling differentially regulates genes such
      as calcineurin, calmodulin kinase II, MAP kinase etc and induces protein
      modifications and neurite degeneration. Since functional synapses and synaptic
      transmission are fundamental processes in memory formation, alterations in these
      processes can lead to neuronal dysfunction and memory deficit as seen in
      Alzheimer's disease. This chapter gives an overview of calcium signaling in
      different systems, specifically neurons, the functioning of pre- and post
      synaptic signaling, and how their deregulation influences pathology development
      in Alzheimer's disease.

PMID- 22453990
TI  - Voltage-gated Ca(2+) channel mediated Ca(2+) influx in epileptogenesis.
AB  - Voltage- and ligand-gated ion channels are key elements in the etiopathogenesis
      of various forms of epilepsy. In this chapter, we present an overview of the
      functional implications of voltage-gated Ca(2+) channels in modulating internal
      Ca(2+) level fluctuations and generating ictiform/epileptiform cellular
      electrophysiological activity. A specific focus will be on the fascinating and
      evolving field of high-voltage activated (HVA) Non-L-type Ca(v)2.3 R-type
      channels and low-voltage activated (LVA) Ca(v)3.1-3.3 T-type Ca(2+) channels in
      the genesis of plateau potentials and excessive rebound bursting. Plateau
      potentials have been characterised in the hippocampus and were shown to be
      triggered by Ca(v)2.3 which subsequently activate CNG channels that mediate long
      lasting plateaus. In the thalamocortical network, a complex ion channel
      armamentarium is involved in regulating a complex balance of burst and tonic mode
      activity. Recent findings point to an outstanding role of R- and T-type channels
      in both thalamocortical eurhythmia and pathophysiological -aberrations. Thus,
      pharmacological modulation of voltage-gated Ca(2+)-channels might prove more and
      more important in treatment of neurological and psychiatric disorder such as
      schizophrenia, mania, dementia and epilepsy.

PMID- 22453987
TI  - Remodeling of calcium handling in human heart failure.
AB  - Heart failure (HF) is an increasing public health problem accelerated by a
      rapidly aging global population. Despite considerable progress in managing the
      disease, the development of new therapies for effective treatment of HF remains a
      challenge. To identify targets for early diagnosis and therapeutic intervention,
      it is essential to understand the molecular and cellular basis of calcium
      handling and the signaling pathways governing the functional remodeling
      associated with HF in humans. Calcium (Ca(2+)) cycling is an essential mediator
      of cardiac contractile function, and remodeling of calcium handling is thought to
      be one of the major factors contributing to the mechanical and electrical
      dysfunction observed in HF. Active research in this field aims to bridge the gap
      between basic research and effective clinical treatments of HF. This chapter
      reviews the most relevant studies of calcium remodeling in failing human hearts
      and discusses their connections to current and emerging clinical therapies for HF
      patients.

PMID- 22453991
TI  - Kinetic and mesoscopic non-equilibrium description of the Ca(2+) pump: a
      comparison.
AB  - We analyse the operation of the Ca(2+)-ATPase ion pump using a kinetic cycle
      diagram. Using the methodology of Hill, we obtain the cycle fluxes, entropy
      production and efficiency of the pump. We compare these results with a mesoscopic
      non-equilibrium description of the pump and show that the kinetic and mesoscopic
      pictures are in accordance with each other. This gives further support to the
      mesoscopic theory, which is less restricted and also can include the heat flux as
      a variable. We also show how motors can be characterised in terms of
      unidirectional backward fluxes. We proceed to show how the mesoscopic approach
      can be used to identify fast and slow steps of the model in terms of activation
      energies, and how this can be used to simplify the kinetic diagram.

PMID- 22453992
TI  - Comparative analysis of the orientation of transmembrane peptides using solid
      state (2)H- and (15)N-NMR: mobility matters.
AB  - Many solid-state nuclear magnetic resonance (NMR) approaches for membrane
      proteins rely on orientation-dependent parameters, from which the alignment of
      peptide segments in the lipid bilayer can be calculated. Molecules embedded in
      liquid-crystalline membranes, such as monomeric helices, are highly mobile,
      leading to partial averaging of the measured NMR parameters. These dynamic
      effects need to be taken into account to avoid misinterpretation of NMR data.
      Here, we compare two common NMR approaches: (2)H-NMR quadrupolar waves, and
      separated local field (15)N-(1)H polarization inversion spin exchange at magic
      angle (PISEMA) spectra, in order to identify their strengths and drawbacks for
      correctly determining the orientation and mobility of alpha-helical transmembrane
      peptides. We first analyzed the model peptide WLP23 in oriented
      dimyristoylphosphatidylcholine (DMPC) membranes and then contrasted it with
      published data on GWALP23 in dilauroylphosphatidylcholine (DLPC). We only
      obtained consistent tilt angles from the two methods when taking dynamics into
      account. Interestingly, the two related peptides differ fundamentally in their
      mobility. Although both helices adopt the same tilt in their respective bilayers
      (~20 degrees ), WLP23 undergoes extensive fluctuations in its azimuthal rotation
      angle, whereas GWALP23 is much less dynamic. Both alternative NMR methods are
      suitable for characterizing orientation and dynamics, yet they can be optimally
      used to address different aspects. PISEMA spectra immediately reveal the presence
      of large-amplitude rotational fluctuations, which are not directly seen by (2)H
      NMR. On the other hand, PISEMA was unable to define the azimuthal rotation angle
      in the case of the highly dynamic WLP23, though the helix tilt could still be
      determined, irrespective of any dynamics parameters.

PMID- 22453994
TI  - Oral microbial colonization in patients with systemic lupus erythematous:
      correlation with treatment and disease activity.
AB  - Treating patients with systemic lupus erythematosus (SLE) with steroids and
      immunosuppressive drugs may interfere in the presence of potentially
      opportunistic microorganisms in the oral cavity. The aim of this study was to
      evaluate the presence of Candida spp., Staphylococcus spp., Enterobacteria and
      Pseudomonas spp. in the oral cavity of SLE patients, compared with healthy
      controls. A group of 40 patients who had received therapy for at least 60 days
      was selected (19-53 years). For the control group, 40 healthy individuals matched
      for age, gender and use of partial prosthesis were selected. Oral rinse samples
      were collected and plated on specific culture media. After incubation, the number
      of colony forming units (CFU) was obtained and the isolates were identified at
      species level. Microbial counts were compared between SLE and control by analysis
      of variance (ANOVA) and Mann-Whitney (p < 0.05 significant). Microorganism counts
      in patients with and without immunosuppressive drugs, as well with active and
      inactive disease (according to SLEDAI score) were also compared. No significant
      differences in CFU/mL between SLE and control patients were observed (yeasts, p =
      0.55; Staphylococci, p = 0.24; Enterobacteria/Pseudomonas spp., p = 0.26). No
      differences in microbial counts were observed regarding clinical parameters
      tested. The most frequent species isolated in the SLE group were Candida
      albicans, Staphylococcus epidermidis and Klebsiella oxytoca. In conclusion, no
      differences in frequency and microorganism levels were found between SLE patients
      and healthy individuals.

PMID- 22453995
TI  - Accuracy of urea breath test performed immediately after emergency endoscopy in
      peptic ulcer bleeding.
AB  - AIMS: The aim of this work is to investigate the accuracy of the urea breath test
      (UBT) performed immediately after emergency endoscopy in peptic ulcer bleeding
      (PUB). METHODS: Urea breath test was carried out right after emergency endoscopy
      in patients with PUB. The accuracy of this early UBT was compared to a delayed
      one after hospital discharge that was considered the gold standard. Clinical and
      epidemiological factors were analyzed in order to study their influence on the
      accuracy of the early UBT. RESULTS: Early UBT was collected without any
      complication and good acceptance from all the 74 patients included. In 53 of the
      patients (71.6%), a delayed UBT was obtained. Comparing concordance between the
      two tests we have calculated an accuracy of 83% for the early UBT. Sensibility
      and specificity were 86.36 and 66%, respectively, with a positive predictive
      value of 92.68% and negative predictive value of 50% (Kappa index = 0.468; p =
      0.0005; CI: 95%). We found no influence of epidemiological factors, clinical
      presentation, drugs, times to gastroscopy, Forrest classification, endoscopic
      therapy, hemoglobin, and urea levels over the accuracy of early UBT. CONCLUSIONS:
      Urea breath test carried out right after emergency endoscopy in PUB is an
      effective, safe, and easy-to-perform procedure. The accuracy of the test is not
      modified by clinical or epidemiological factors, ulcer stage, or by the type of
      therapy applied. However, we have found a low negative predictive value for early
      UBT, so a delayed test is mandatory for all negative cases.

PMID- 22453996
TI  - Survival in elderly patients with ulcerative colitis and colorectal cancer.

PMID- 22453997
TI  - Combined ERCP and EUS in one session is safe in elderly patients when compared to
      non-elderly patients: outcomes in 206 combined procedures.
AB  - AIMS: Combined ERCP/EUS is becoming common. Combined procedures are frequently
      performed in elderly patients. We hypothesized that combined ERCP/EUS is equally
      safe in elderly patients when compared to non-elderly patients. METHODS: This was
      a retrospective single-center study comparing outcomes in elderly and non-elderly
      patients undergoing combined ERCP/EUS. RESULTS: A total of 206 patients were
      included. Mean age was 65 years (M:F 113:93); 99 were <65 years and 107 were >65.
      Indications included: jaundice (51%), abnormal imaging (17%), pancreatic tumor
      (11%), abdominal pain (5%), stent placement/change (5%), acute or chronic
      pancreatitis (5%), other (6%). Fine needle aspiration was performed in 134 (65%)
      procedures. Malignancy was identified in 142/206 (69%) patients. Mean Charlson
      Comorbidity Index (CCI) was 7.5 (range 0-22). Among patients <65 years old there
      were no immediate adverse events. Long-term adverse events in patients <65
      (within 30 days) included cholangitis (1), increasing abdominal pain (4), post
      ERCP pancreatitis (3), nausea/vomiting (1), increasing fatigue (1), and
      increasing jaundice (1). A subgroup analysis among geriatric patients (>65) was
      performed. Mean CCI was 8.2 (range 0-22). There was one immediate adverse event
      of non-sustained ventricular tachycardia in a 76-year old. Long-term adverse
      events included increasing fatigue (1), nausea/vomiting (2), increasing abdominal
      pain (2), urosepsis (1), fever (2) and dehydration (1). There were no
      statistically significant differences in outcomes in elderly compared to non
      elderly patients. Elderly patients had higher CCI scores (p = 0.04). CONCLUSION:
      Combined ERCP/EUS in one session is safe in the general population and elderly
      patients, with no more adverse events than in non-elderly patients.

PMID- 22453998
TI  - Customization of Aspergillus niger morphology through addition of talc micro
      particles.
AB  - The filamentous fungus A. niger is a widely used strain in a broad range of
      industrial processes from food to pharmaceutical industry. One of the most
      intriguing and often uncontrollable characteristics of this filamentous organism
      is its complex morphology. It ranges from dense spherical pellets to viscous
      mycelia. Various process parameters and ingredients are known to influence fungal
      morphology. Since optimal productivity correlates strongly with a specific
      morphological form, the fungal morphology often represents the bottleneck of
      productivity in industrial production. A straight forward and elegant approach to
      precisely control morphological shape is the addition of inorganic insoluble
      micro particles (like hydrous magnesium silicate, aluminum oxide or titanium
      silicate oxide) to the culture medium contributing to increased enzyme
      production. Since there is an obvious correlation between micro particle
      dependent morphology and enzyme production it is desirable to mathematically link
      productivity and morphological appearance. Therefore a quantitative precise and
      holistic morphological description is targeted. Thus, we present a method to
      generate and characterize micro particle dependent morphological structures and
      to correlate fungal morphology with productivity which possibly contributes to a
      better understanding of the morphogenesis of filamentous microorganisms. The
      recombinant strain A. niger SKAn1015 is cultivated for 72 h in a 3 L stirred tank
      bioreactor. By addition of talc micro particles in concentrations of 1 g/L, 3 g/L
      and 10 g/L prior to inoculation a variety of morphological structures is
      reproducibly generated. Sterile samples are taken after 24, 48 and 72 hours for
      determination of growth progress and activity of the produced enzyme. The formed
      product is the high-value enzyme beta-fructofuranosidase, an important
      biocatalyst for neo-sugar formation in food or pharmaceutical industry, which
      catalyzes among others the reaction of sucrose to glucose. Therefore, the
      quantification of glucose after adding sucrose implies the amount of produced
      beta-fructofuranosidase. Glucose quantification is made by a GOD/POD-Assay, which
      is modified for high-throughput analysis in 96-well micro titer plates. Fungal
      morphology after 72 hours is examined by microscope and characterized by digital
      image analysis. In doing so, particle shape factors for fungal macro morphology
      like Feret's diameter, projected area, perimeter, circularity, aspect ratio,
      roundness und solidity are calculated with the open source image processing
      program ImageJ. Relevant parameters are combined to a dimensionless Morphology
      number (Mn), which enables a comprehensive characterization of fungal morphology.
      The close correlation of the Morphology number and productivity are highlighted
      by mathematical regression.

PMID- 22454000
TI  - A new age has come: the redefinition of women's health care.

PMID- 22454001
TI  - Multidrug-resistant gonorrhoea: tackling a meaner bug in the UK.

PMID- 22454003
TI  - Contraceptive efficacy and tolerability of ethinylestradiol 20 MUg/drospirenone 3
      mg in a flexible extended regimen: an open-label, multicentre, randomised,
      controlled study.
AB  - BACKGROUND: The contraceptive efficacy and tolerability of a new flexible
      extended regimen of ethinylestradiol (EE) 20 MUg/drospirenone (DRSP) 3 mg to
      extend the menstrual cycle and enable management of intracyclic (breakthrough)
      bleeding (flexible(MIB)) was investigated and the bleeding pattern compared with
      a conventional 28-day regimen and a fixed extended 124-day regimen. STUDY DESIGN:
      This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated
      women (aged 18-35 years) to the following regimens: flexible(MIB) (24-120 days'
      active hormonal intake with 4-day tablet-free intervals); conventional (24 days'
      active hormonal intake followed by a 4-day hormone-free interval); or fixed
      extended (120 days' uninterrupted active hormonal intake followed by a 4-day
      tablet-free interval). Primary outcomes included the number of bleeding/spotting
      days during Year 1 (all regimens) and the number of observed unintended
      pregnancies over 2 years (flexible(MIB) only). RESULTS: Results were analysed in
      1067 women (full analysis set). The mean number of bleeding/spotting days was
      lower with the flexible(MIB) vs the conventional regimen [41.0+/-29.1 (95% CI
      38.8-43.3) vs 65.8+/-27.0 (95% CI 62.2-69.4) days, p<0.0001; treatment difference
      -24.8 (95% CI -29.2 to -20.3) days]. The corresponding value for the fixed
      extended regimen was 60.9+/-51.1 (95% CI 53.9-67.9) days. The Pearl Index for the
      flexible(MIB) regimen was 0.64 (95% CI 0.28-1.26). All regimens had comparable
      tolerability profiles. CONCLUSIONS: EE 20 MUg/DRSP 3 mg administered as a
      flexible extended regimen with MIB is effective, well tolerated and is associated
      with statistically significantly fewer bleeding/spotting days and fewer
      withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The
      flexible(MIB) also provided statistically significantly fewer spotting days vs
      EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The
      flexible(MIB) regimen allows women to extend their menstrual cycle and manage
      their intracyclic (breakthrough) bleeding.

PMID- 22454004
TI  - Long-term tolerability of ethinylestradiol 20 MUg/drospirenone 3 mg in a flexible
      extended regimen: results from a randomised, controlled, multicentre study.
AB  - BACKGROUND: This study was designed to assess the long-term safety and
      tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20
      MUg/drospirenone (DRSP) 3 mg, which allows management of intracyclic
      (breakthrough) bleeding [flexible management of intracyclic (breakthrough)
      bleeding (MIB)], in comparison to conventional 28-day and fixed extended
      regimens. STUDY DESIGN: In this Phase III, multicentre, open-label study, women
      (aged 18-35 years) were randomised to EE/DRSP in the following regimens:
      flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet
      free interval), conventional 28-day (24 days' active hormonal intake followed by
      a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active
      hormonal intake followed by a 4-day tablet-free interval) during a 1-year
      comparative phase. Thereafter, women entered a 1-year safety extension phase in
      which the majority received the flexible(MIB) regimen. Safety/tolerability
      outcomes were measured over 2 years. A separate analysis of certain safety
      parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables)
      was conducted at two of the study centres. RESULTS: Results were analysed in 1067
      and 783 women in the comparative and safety extension phases. Overall, 56.3% of
      women experienced >=1 adverse event (AE) in the safety extension phase. Serious
      AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB),
      conventional and fixed extended regimens, respectively. No unexpected
      endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any
      of the three regimens. CONCLUSIONS: EE/DRSP in a flexible extended regimen with
      management of intracyclic (breakthrough) bleeding is well-tolerated and, when
      administered for up to 2 years, has a good safety profile comparable to other
      estrogen/progestogen oral contraceptives.

PMID- 22454006
TI  - Efficacy of ethinylestradiol 20 MUg/drospirenone 3 mg in a flexible extended
      regimen in women with moderate-to-severe primary dysmenorrhoea: an open-label,
      multicentre, randomised, controlled study.
AB  - OBJECTIVES: The aim of this Phase III, multicentre, open-label, randomised study
      was to compare the efficacy and safety of ethinylestradiol (EE)/drospirenone
      (DRSP) in a new flexible extended regimen that allowed the management of
      intracyclic (breakthrough) bleeding (MIB) with that of EE/DRSP in a conventional
      28-day regimen in women with moderate-to-severe primary dysmenorrhoea. METHODS:
      Women (aged 18-40 years) with moderate-to-severe primary dysmenorrhoea-related
      pain received a flexible extended regimen with MIB (flexible(MIB); minimum 24,
      maximum 120 days of continuous tablet intake for a flexible number of cycles to
      reach a treatment duration of at least 140 days with 4-day breaks between cycles)
      or a conventional 28-day regimen (24 active and four placebo tablets for five
      cycles) of EE/DRSP. The primary outcome was the number of days with
      dysmenorrhoeic pain over 140 days. Secondary outcomes included other
      dysmenorrhoea-related pain outcomes, bleeding profile, satisfaction and safety.
      RESULTS: Overall, 223 patients received study medication. There were
      significantly fewer days with dysmenorrhoeic pain with the flexible(MIB) regimen
      than the conventional regimen (difference -4.2 days, 95% CI -6.5 to -2.0;
      p=0.0003), as well as considerably fewer days with at least moderate
      dysmenorrhoeic pain (difference -2.5 days, 95% CI -3.7 to -1.3), dysmenorrhoeic
      pain that interfered with daily activities (difference -2.2 days, 95% CI -4.2 to 
      0.1) and pelvic pain (difference -3.4 days, 95% CI -5.9 to -0.9). Adverse events
      were similar with both regimens. CONCLUSIONS: Compared with the conventional
      regimen, the flexible extended regimen of EE/DRSP with MIB was associated with a
      significantly greater reduction in days with dysmenorrhoeic pain in women with
      moderate-to-severe primary dysmenorrhoea. The flexible(MIB) regimen was also
      associated with greater improvements in dysmenorrhea according to the Clinical
      Global Impression rating scale and was generally well tolerated.

PMID- 22454008
TI  - Abortion pills: under whose control?

PMID- 22454010
TI  - Doulas as facilitators: the expanded role of doulas into abortion care.

PMID- 22454011
TI  - Abortion in the classical world.

PMID- 22454012
TI  - Gods no longer? Some thoughts about the status of health professionals in the
      21st century.

PMID- 22454013
TI  - Seems like a touch too much.

PMID- 22454014
TI  - The renaissance of barrier methods.
AB  - In 1987, the threat of litigation led to the withdrawal of intrauterine devices
      (IUDs)from the American market where depot medroxyprogesterone acetate (DMPA)had
      already been banned. There were fears of repercussions that would have led to the
      limiting of contraceptive choice in Britain. HIV was also an emerging issue and a
      revival of interest in barrier contraception led to an emphasis on male condoms,
      with strengthening of manufacturing standards, promotion in the media,improved
      accessibility and emphasis of their value for dual protection. Twenty-five years
      later, links still need to be sought within reproductive health services,
      especially at the interface between the management of contraception and
      opportunities for HIV prevention.

PMID- 22454015
TI  - Jo's Cervical Cancer Trust.

PMID- 22454016
TI  - Reanalysis of data from the Million Women Study.

PMID- 22454017
TI  - What really matters is the menopausal woman!

PMID- 22454018
TI  - Difference between drospirenone-containing oral contraceptives and other oral
      contraceptives related to risk of venous thromboembolism.

PMID- 22454019
TI  - Challenge of HIV testing in low prevalence settings.

PMID- 22454020
TI  - HIV testing in abortion services.

PMID- 22454021
TI  - Routine HIV testing in colposcopy.

PMID- 22454022
TI  - Emergency contraception prescribing in a GUM clinic: missed opportunities for
      improving sexual and reproductive health.

PMID- 22454023
TI  - Unintended pregnancy with subdermal implant following miscarriage: response to
      Rank letter.

PMID- 22454024
TI  - Psychosexual bodywork: should we refer our patients, and if so why?

PMID- 22454026
TI  - First name, surname or number: how to call a patient in the waiting room?

PMID- 22454027
TI  - Experiences and perceptions of Muslim and non-Muslim women during prenatal
      screening: a comparative study in Flanders and Brussels, Belgium.

PMID- 22454028
TI  - Short-term complications of the Mirena(R) IUS vs the copper IUD in Muslim women.

PMID- 22454029
TI  - Profile of female sterilisation clients at eight clinics in Eastern India.

PMID- 22454030
TI  - Factors influencing caregivers' burden among family caregivers and
      institutionalization of in-home elderly people cared for by family caregivers.
AB  - OBJECTIVES: The purpose of this study was to determine the factors related to
      changes in the burden of caregivers who look after the elderly at home, as well
      as factors related to the institutionalization of the elderly who require care.
      The types of care services associated with reducing caregivers' burden and
      continuing in-home care were also studied. METHODS: The study subjects were
      adults aged >=65 years who used the services of in-home care management centres
      located in Osaka Prefecture, Japan, and their caregivers. This 2-year
      longitudinal study began in October 2007, with a total of three surveys
      undertaken once a year. The survey methods included self-administered
      questionnaires and the review of clinical records. RESULTS: Dementia and its
      accompanying behavioural disturbances were found to be significantly related to
      the increased burden of caregivers and the institutionalization of those
      requiring care. A significantly higher proportion of caregivers with an
      increasing burden or those who maintained a high level of burden used day care
      services compared to those in the other groups. CONCLUSION: Preventive
      intervention against dementia and its accompanying behavioural disturbances
      should be considered in the day care service to reduce caregivers' burden and to
      decrease institutionalization.

PMID- 22454032
TI  - Revisiting the homology modeling of G-protein coupled receptors: beta1
      adrenoceptor as an example.
AB  - G-protein coupled receptors (GPCRs) are recognized to constitute the largest
      family of membrane proteins. Due to the disproportion in the quantity of crystal
      structures and their amino acid sequences, homology modeling contributes a
      reasonable and feasible approach to GPCR theoretical coordinates. With the brand
      new crystal structures resolved recently, herein we deliberated how to designate
      them as templates to carry out homology modeling in four aspects: (1) various
      sequence alignment methods; (2) protein weight matrix; (3) different sets of
      multiple templates; (4) active and inactive state of templates. The accuracy of
      models was evaluated by comparing the similarity of stereo conformation and
      molecular docking results between models and the experimental structure of
      Meleagris gallopavo beta(1)-adrenergic receptor (Mg_Adrb1) that we desired to
      develop as an example. Our results proposed that: (1) Cobalt and MAFFT, two
      algorithms of sequence alignment, were suitable for single- and multiple-template
      modeling, respectively; (2) Blosum30 is applicable to align sequences in the case
      of low sequence identity; (3) multiple-template modeling is not always better
      than single-template one; (4) the state of template is an influential factor in
      simulating the GPCR structures as well.

PMID- 22454033
TI  - Ammine aluminium borohydrides: an appealing system releasing over 12 wt% pure H2
      under moderate temperature.
AB  - Ammine aluminium borohydride system is found to release >12 wt% pure H(2) below
      120  degrees C via a combined strategy of changing the coordination number and
      adopting mixed cations.

PMID- 22454034
TI  - A mathematical model for astrocytes mediated LTP at single hippocampal synapses.
AB  - Many contemporary studies have shown that astrocytes play a significant role in
      modulating both short and long form of synaptic plasticity. There are very few
      experimental models which elucidate the role of astrocyte over Long-term
      Potentiation (LTP). Recently, Perea and Araque (Science 317:1083-1086, 2007)
      demonstrated a role of astrocytes in induction of LTP at single hippocampal
      synapses. They suggested a purely pre-synaptic basis for induction of this N
      methyl-D-Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms
      underlying this pre-synaptic induction were not investigated. Here, in this
      article, we propose a mathematical model for astrocyte modulated LTP which
      successfully imitates the experimental findings of Perea and Araque (Science
      317:1083-1086, 2007). Our study suggests the role of retrograde messengers,
      possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.

PMID- 22454035
TI  - Effect of silencing HIF-1alpha on proliferation, invasion and migration of
      glioblastoma U87 cells.
AB  - The objective of the study was to evaluate the effect of silencing hypoxia
      inducible factor 1alpha (HIF-1alpha) on proliferation, invasion, and migration of
      glioblastoma U87 cells. HIF-1alpha-shRNA lentiviral vector was designed for
      liposome-mediated transfection into U87 cells. The efficiency of interference was
      assessed by RT-PCR and Western blot. Cell proliferation was measured by MTT
      assay. Cell migration was observed by the migration test. The capabilities of
      invasion and migration were detected using the Transwell model. The research
      involved experiments in the interference group (shRNA transfected), the control
      interference group (empty vector transfected), and the untreated (non
      transfected) group. Compared with the control interference group and the
      untreated group, the expressions of HIF-1alpha mRNA and protein were
      significantly down-regulated, and the proliferation and invasion of U87 cells
      were significantly inhibited in the interference group. HIF-1alpha mRNA and
      protein are effectively suppressed by HIF-1alpha-shRNA in U87 cells, which
      appears to inhibit proliferation, invasion, and migration of U87 cells.

PMID- 22454036
TI  - Long-term clinical and radiological evolution in one case of Susac's syndrome.
AB  - Susac's syndrome is a rare idiopathic microangiopathy affecting the precapillary
      arterioles of the brain, retina and cochlea leading to the clinical triad of
      encephalopathy, retinopathy and hearing loss. The objective of this study is to
      describe a new case of Susac's syndrome reactivated after a 12-year period with a
      good response to immunosuppressive therapy. The patient was a 32-year-old woman,
      complaining of diplopia, right blurred vision, progressive gait disturbance,
      tinnitus, attention deficit, and slight memory loss. The patient was diagnosed as
      having Susac's syndrome and discharged with steroid therapy. After a 12-year
      period of clinical stability she had a relapse. Immunosuppressive therapy
      resulted in significant clinical and radiological improvement. Early clinical
      identification of Susac's syndrome is crucial for the initiation of
      immunosuppressive therapy and differential diagnosis. In our case, the combined
      use of corticosteroids and azathioprine was key in the relapse management.

PMID- 22454037
TI  - Evaluation of an institutional guideline for the treatment of cerebrospinal fluid
      shunt-associated infections.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) shunt-associated infection is one of the
      most frequent complications of CSF shunt surgery. We evaluated our institutional
      guideline for the treatment of shunt-associated infections. METHODS: We
      retrospectively analysed all 92 episodes of shunt-associated infections in 78
      patients treated in our institution from 2002 to 2008. All patients underwent
      urgent surgery, i.e. removal of the complete shunt hardware or externalisation of
      the distal tubing in cases with an infection restricted to the distal shunt (10
      %), placement of an external ventricular drainage as necessary and antibiotic
      therapy. Standard empirical first-line antibiotic treatment consisted of a
      combination of flucloxacillin and cefuroxime. RESULTS: We observed 38 % early (<1
      month after shunt surgery) and 20 % late infections (> 1 year after shunt
      placement). Coagulase-negative staphylococci (CoNS) were isolated in 38 %. In 38
      % no pathogens could be isolated. Of cases with a first shunt infection, 58 %
      were initially treated with flucloxacillin/cefuroxime. Only 53 % of all
      infections were treated successfully with the first course of antibiotics. Only
      51 % of bacterial isolates were sensitive to empirical first-line antibiotics.
      Twenty percent of infections caused by sensitive bacterial isolates nevertheless
      required second-line antibiotic therapy. CONCLUSIONS: Urgent surgery for shunt
      removal and antibiotic therapy will usually cure a shunt-associated infection.
      The choice of antibiotics should reflect the spectrum of pathogens seen at one's
      institution, paying particular attention to the role of CoNS isolates, and in
      vitro sensitivity testing results.

PMID- 22454038
TI  - Effect of cervical spinal cord electrical stimulation on nitric oxide levels in
      brain and dermal tissues: an evaluation using by real-time nitric oxide
      measurement.
AB  - OBJECTIVE: Nitric oxide synthesized from L: -arginine via the nitric oxide
      synthase enzyme family is the main regulatory molecule in many physiological
      systems. The level of nitric oxide can now be measured in tissues by a direct
      real-time amperometric method. The effect of electrical stimulation of the upper
      cervical spine on the arteries that supply the brain and upper extremities has
      been established by experimental studies, and thus it has begun to be used in
      clinical practice to increase blood flow in the brain and the peripheral vascular
      system. The mechanism of this effect is still a subject of research. This is the
      first report of real-time nitric oxide measurement in living brain and dermal
      tissue during electrical stimulation of the upper cervical spine. METHODS: Using
      the amperometric method, nitric oxide levels in frontal subcortical and front
      foot skin were measured before, during and after electrical stimulation of the
      upper cervical spine in three groups of rabbits that received infusions of saline
      solution, 7-aminoguanidine or atropine. RESULTS: By electrical stimulation,
      tissue nitric oxide levels increased significantly and remained increased during
      stimulation in the brain and skin. The nitric oxide levels dropped back to normal
      value 1 min after stimulation was turned off. CONCLUSION: The results we obtained
      have showed that real-time nitric oxide could also be measured by an amperometric
      method in living tissues like brain. The effect of stimulation on nitric oxide
      levels of living tissues disappears immediately when the stimulation is turned
      off.

PMID- 22454039
TI  - The endocannabinoids anandamide and virodhamine modulate the activity of the
      candidate cannabinoid receptor GPR55.
AB  - The role of cannabinoid receptors in inflammation has been the topic of many
      research endeavors. Despite this effort, to date the involvement of the
      endocannabinoid system (ECS) in inflammation remains obscure. The ambiguity of
      cannabinoid involvement may be explained by the existence of cannabinoid
      receptors, other than CB(1) and CB(2), or a consequence of interaction of
      endocannabinoids with other signaling systems. GPR55 has been proposed to be a
      cannabinoid receptor; however the interaction of the endocannabinoid system with
      GPR55 remains elusive. Consequently this study set about to examine the effects
      of the endocannabinoids, anandamide (AEA) and virodhamine, on GPR55 mediated
      signaling. Specifically, we assessed changes in beta-arrestin2 (betaarr2)
      distribution and GPR55 receptor internalization following activation by
      lysophosphatidylinositol (LPI), the synthetic cannabinoid ligand SR141716A, and
      new selective synthetic GPR55 agonists. Data obtained from the experiments
      presented herein demonstrate that AEA and virodhamine modulate agonist-mediated
      recruitment of betaarr2. AEA and virodhamine act as partial agonists; enhancing
      the agonist effect at low concentrations and inhibiting it at high
      concentrations. Furthermore, both virodhamine and AEA significantly attenuated
      agonist-induced internalization of GPR55. These effects are attributed to the
      expression of GPR55, and not CB(1) and CB(2) receptors, as we have established
      negligible expression of CB(1) and CB(2) in these GPR55-transfected U2OS cells.
      The identification of select endocannabinoids as GPR55 modulators will aide in
      elucidating the function of GPR55 in the ECS.

PMID- 22454040
TI  - Anti-inflammatory effects of ladostigil and its metabolites in aged rat brain and
      in microglial cells.
AB  - Impaired mitochondrial function accompanied by microglial activation and the
      release of nitric oxide (NO) and pro-inflammatory cytokines has been reported in
      Alzheimer's disease, its prodromal phase of Mild Cognitive Impairment (MCI) and
      in aged rats. The present study showed that 6 months treatment of 16 month old
      rats with ladostigil (1 mg/kg/day), a novel drug designed for the treatment of
      MCI, prevented the development of spatial memory deficits at 22 months of age and
      significantly decreased the gene expression of IL-1beta, IL-6, TNF-alpha and
      inducible nitric oxide synthase (iNOS) in the parietal cortex. It was also shown
      that concentrations ranging from 1nM-1 MUM of ladostigil and three of its active
      metabolites inhibited the release of nitric oxide (NO) induced by
      lipopolysaccharide (LPS) from mouse microglial cells by up to 35-40 %. Ladostigil
      and its metabolites (10nM) also reduced TNF-alpha mRNA and protein by 25-35 % and
      IL-1beta and inducible nitric oxide synthase (iNOS) mRNA by 20-35 %. The
      concentration of 10nM is in the range of that of the parent drug, R-MCPAI and R
      HPAI found in plasma after oral administration of ladostigil (1 mg/kg/day) to
      rats. All the compounds inhibited the degradation of IkB-alpha and nuclear
      translocation of the p65 subunit of NF-kB. They also inhibited phosphorylation of
      p38 and ERK1/2 mitogen-activated protein kinase (MAPK), but had no effect on that
      of JNK. We propose that the anti-inflammatory activity may contribute towards the
      neuroprotective action of ladostigil against the development of memory
      impairments induced by aging or toxin-induced microglial activation.

PMID- 22454042
TI  - Tunable bands in biased multilayer epitaxial graphene.
AB  - We have studied the electronic characteristics of multilayer epitaxial graphene
      under a perpendicularly applied electric bias. Ultraviolet photoemission
      spectroscopy measurements reveal that there is notable variation of the
      electronic density-of-states in valence bands near the Fermi level. Evolution of
      the electronic structure of graphite and rotational-stacked multilayer epitaxial
      graphene as a function of the applied electric bias is investigated using first
      principles density-functional theory including interlayer van der Waals
      interactions. The experimental and theoretical results demonstrate that the
      tailoring of electronic band structure correlates with the interlayer coupling
      tuned by the applied bias. The implications of controllable electronic structure
      of rotationally fault-stacked epitaxial graphene grown on the C-face of SiC for
      future device applications are discussed.

PMID- 22454043
TI  - Sleep deprivation in ICU.

PMID- 22454041
TI  - Wnt/beta-catenin signaling in glioma.
AB  - Extensive data have shown that Wnt/beta-catenin signaling is associated with
      various disease pathologies, including an important role in tumorigenesis. Here,
      we review the regulation of Wnt/beta-catenin signaling in glioma, with particular
      focus on the expression signatures of the main components in Wnt/beta-catenin
      signaling, the role of key factors in Wnt/beta-catenin signaling, and crosstalk
      with other signaling pathways. Finally, we discuss the involvement of microRNAs
      in Wnt/beta-catenin signaling in glioma. This review reveals new insights into
      the role of Wnt/beta-catenin signaling in gliomagenesis, and highlights new
      therapeutic approaches for glioma, based on the modulation of the Wnt/beta
      catenin pathway.

PMID- 22454044
TI  - Myths and facts in neuromuscular pharmacology. New developments in reversing
      neuromuscular blockade.
AB  - Pharmacologic reversal of neuromuscular blockade is a topic not very well
      acknowledged and controversially discussed. Reasons for this are numerous and
      include missing perception of the potential complications of residual
      neuromuscular paralysis including an increased morbidity and mortality, as well
      as low efficacy and numerous unwanted side effects of the available antagonists.
      Duration of action of muscle relaxants cannot be pharmacologically predicted.
      Objective neuromuscular monitoring is the only way to detect residual paralysis.
      This review article would like to discuss in its first part some of the myths
      which revolve around the use of muscle relaxants, then highlight the problems
      regarding the use of acetylcholine esterase inhibitors and, in the third part,
      discuss the steroidal muscle relaxant encapsulator sugammadex.

PMID- 22454046
TI  - Constraints on haplotype structure and variable gene frequencies suggest a
      functional hierarchy within cattle MHC class I.
AB  - Six major histocompatibility complex (MHC) classical class I genes have been
      identified in cattle, and up to three of these are expressed in variable
      combinations on different haplotypes. The origin and functional significance of
      this genetic complexity is unknown. However, an improved assembly of the cattle
      genome, an expanded database of full-length cDNA sequences and high-resolution
      frequency data concerning expressed class I genes in an economically important
      cattle breed combine to provide a new opportunity to study the significance of
      cattle MHC class I diversity. Analysis of these new data supports assignment of
      alleles to six discrete genes and further shows that all these classical genes
      share a common ancestor with a single non-classical gene, NC1. While haplotype
      structure is variable, with thirteen gene configurations identified, there are
      nevertheless clear constraints relating to both the number and combination of
      genes. Haplotypes expressing two classical genes are most frequently observed,
      and the classical class I gene 2 is almost invariably present. The frequency data
      support the dominance of gene 2, showing that close to 100 % of individuals carry
      at least one copy. This indicates a hierarchy in the functional importance of
      particular genes and haplotype structures. Haplotype frequency in cattle
      populations is therefore likely to impact on differential disease
      susceptibilities. This knowledge will be important for development of informed
      breeding strategies aimed at increasing the ability of cattle to survive in the
      face of future unpredictable pathogen exposure.

PMID- 22454045
TI  - Acute versus chronic hypoxia in tumors: Controversial data concerning time frames
      and biological consequences.
AB  - BACKGROUND: Many tumors contain hypoxic regions. Hypoxia, in turn, is known to
      increase aggressiveness and to be associated with treatment resistance. The two
      most frequently described and investigated subtypes of tumor hypoxia are acute
      and chronic. These two subtypes can lead to completely different hypoxia-related
      responses within the tumor, which could have a direct effect on tumor development
      and response to treatment. In order to accurately assess the specific biological
      consequences, it is important to understand which time frames best define acute
      and chronic hypoxia. MATERIALS AND METHODS: This article provides an overview of
      the kinetics of in vitro and in vivo acute and chronic tumor hypoxia. Special
      attention was paid to differentiate between methods to detect spontaneous in vivo
      hypoxia and to describe the biological effects of experimental in vitro and in
      vivo acute and chronic tumor hypoxia. RESULTS AND CONCLUSIONS: There are large
      variations in reported spontaneous fluctuations in acute hypoxia that are
      dependent on the cell lines investigated and the detection method used. In
      addition to differing hypoxia levels, exposure times used to induce in vitro and
      in vivo experimental acute and chronic hypoxia range from 30 min to several weeks
      with no clear boundaries separating the two. Evaluation of the biological
      consequences of each hypoxia subtype revealed a general trend that acute hypoxia
      leads to a more aggressive phenotype. Importantly, more information on the
      occurrence of acute and chronic hypoxia in human tumors is needed to help our
      understanding of the clinical consequences.

PMID- 22454047
TI  - The relationship between acoustic startle response measures and cognitive
      functions in Japanese patients with schizophrenia.
AB  - Recently, schizophrenia endophenotypes have been actively investigated to better
      understand the pathophysiology of schizophrenia. Past studies have shown that
      cognitive functions, including working memory and executive function, correlate
      with acoustic startle responses, such as prepulse inhibition (PPI), in patients
      with schizophrenia. The aim of this study was to investigate the relationship
      between cognitive functions and acoustic startle response in Japanese patients
      with schizophrenia. In 100 patients with schizophrenia, we evaluated cognitive
      function, using the Brief Assessment of Cognition in Schizophrenia, Japanese
      language version (BACS-J), and acoustic startle responses, including acoustic
      startle reflex, habituation, and PPI (three different intensities: 82, 86, and 90
      dB SPL, equivalent to signal-to-noise ratios of +12, +16, and +20 dB,
      respectively). Using multiple regression analysis, we examined the relationship
      between acoustic startle responses and BACS-J primary measures or composite
      score. Level of attention was associated with magnitude of habituation in
      schizophrenia (P = 0.0009, beta = -0.357). None of the other domains of cognitive
      function were significantly associated with any measure of acoustic startle
      response. This included attention regarding ASR (P = 0.513), PPI (P = 0.521
      0.842), verbal memory (P = 0.423-0.981), working memory (P = 0.312-0.966), motor
      speed (P = 0.323-0.955), verbal fluency (P = 0.125-0.920), executive function (P
      = 0.118-0.470), and the BACS-J composite score (P = 0.230-0.912). In this first
      investigation of the relationship between cognitive functions and acoustic
      startle responses in Japanese patients with schizophrenia, attentional deficits
      correlated highly with the level of habituation. However, a replication study
      using other population samples is required to further investigate this
      relationship.

PMID- 22454049
TI  - Separate estimation of N export into baseline N leakage without disturbance and N
      loss due to insect defoliation in a pine forest watershed in central Japan.
AB  - Pine wilt disease (PWD) is caused by a non-native pest that has spread
      extensively throughout Japan. Previous research has indicated that most infected
      trees have died and the litter deposited has resulted in changes to stream-water
      chemistry, particularly increased nitrate (NO(3)(-)) concentrations. In this
      study, we divided stream nitrogen (N) export into N loss due to PWD and baseline
      N leakage without disturbance based on long-term monitoring. The annual N export
      was 110.0 mol N ha(-1) year(-1) in 1990 and 749.8 mol N ha(-1) year(-1) in 1997,
      and had decreased to 37.0 mol N ha(-1) year(-1) in 2005. N export under PWD
      influence was estimated to be 3697 mol N ha(-1), and N loss due to PWD was 2810
      mol N ha(-1). N loss due to PWD was three times larger than baseline N leakage
      for the disturbed period. These changes in plant-herbivore relationships could
      affect N status in a forest ecosystem. So-called "semi-natural" disturbances
      related to non-native species invasion and increases of atmospheric N deposition
      caused by human activity will increase. Long-term monitoring studies of various
      aspects are necessary to offer insight into this ecosystem.

PMID- 22454048
TI  - Additional colectomy after colonoscopic polypectomy for T1 colon cancer: a fine
      balance between oncologic benefit and operative risk.
AB  - PURPOSE: The treatment of early-stage colorectal cancers removed endoscopically
      depends on histopathologic findings. This study aimed to assess the benefit-risk
      balance for patients who underwent additional surgery after endoscopic resection
      of a T1 carcinoma with unfavorable histology. METHODS: From 2000 to 2010, 64
      consecutive patients were included in this retrospective study. Specimens
      resected after endoscopic polypectomy showed at least one of the following
      unfavorable factors: no free margin, lymphovascular invasion, poorly
      differentiated grade, SM2-3 involvement (submucosal invasion greater than 300 MUm
      from the muscularis mucosae), tumor budding, sessile morphology, and piecemeal
      resection. The main objective was to assess the benefit-risk balance of an
      oncological resection performed after the polypectomy. Oncological benefit was
      measured by the lymph node metastasis rate and the persistence of a residual
      adenocarcinoma on the specimen. The risk was measured by the occurrence of severe
      complications of grade III-IV or death. The associations between these end points
      and clinicopathologic variables were evaluated by univariate analysis and
      logistic regression. RESULTS: Five patients (7.8 %) had lymph node metastases and
      two (3.1 %) had residual carcinomas. Eight patients (12.5 %) had grade III-IV
      morbidity. There were no deaths. Oncological benefit was associated by logistic
      regression analysis with patients who presented multiple criteria (>=2) that led
      to surgery (p = 0.031). The benefit-risk balance was favorable only for those
      patients. CONCLUSIONS: Additional surgery is required for patients who present
      multiple adverse histological criteria. If only one criterion is selected, the
      indication should be discussed, especially for patients with multiple
      comorbidities.

PMID- 22454050
TI  - Source apportionment of polycyclic aromatic hydrocarbons in the Dahuofang
      Reservoir, Northeast China.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in 24 surface sediments from the
      Dahuofang Reservoir (DHF), the largest man-made lake in Northeast China, were
      measured. The results showed that the concentrations of 16 US EPA priority PAHs
      in the sediments ranged from 323 to 912 ng/g dry weight with a mean concentration
      of 592 +/- 139 ng/g. The PAH source contributions were estimated based on
      positive matrix factorization model. The coal combustion contributed to 31 % of
      the measured PAHs, followed by residential emissions (22%), biomass burning
      (21%), and traffic-related emissions (10%). Pyrogenic sources contributed ~84% of
      anthropogenic PAHs to the sediments, indicating that energy consumption release
      was a predominant contribution of PAH pollution in DHF. Compared with the results
      from the urban atmospheric PAHs in the region, there was a low contribution from
      traffic-related emissions in the sediments possibly due to the low mobility of
      the traffic-related derived 5+6-ring PAHs and their rapid deposition close to the
      urban area.

PMID- 22454051
TI  - DNA diagnostics and exon skipping.
AB  - The predominate form of DNA diagnostics remains nucleic acid sequencing in the
      research and clinical setting. While DNA sequencing allows a mutation to be
      correctly identified, only RNA sequencing can confirm the effect of that mutation
      on the resulting mRNA transcript. In the absence of RNA sequencing, predictions
      are reliant on either experimental studies or bioinformatic modelling. While each
      of these approaches provides insights into cellular splicing choices, of which
      exon skipping is but one, both possess inherent weaknesses. A method which is
      able to integrate and appropriately weigh the various factors influencing
      cellular splicing choices into an accurate, comprehensive modelling tool still
      remains elusive.In this overview chapter, the current methods utilised for DNA
      diagnostics and the impact of the emerging next-generation sequencing techniques
      are considered. We explore why RNA remains a problematic medium with which to
      work. To understand how exon skipping can be predicted from a DNA sequence, the
      key cis-acting elements influencing splicing are reviewed. Finally, the current
      methods used to predict exon skipping including RNA-based studies, experimental
      studies, and bioinformatic modelling approaches are outlined.

PMID- 22454052
TI  - Bioinformatics and mutations leading to exon skipping.
AB  - Our knowledge about human genes and the consequences of mutations leading to
      human genetic diseases has drastically improved over the last few years. It has
      been recognized that many mutations are indeed pathogenic because they impact the
      mRNA rather than the protein itself. With our better understanding of the very
      complex mechanism of splicing, various bioinformatics tools have been developed.
      They are now frequently used not only to search for sequence motifs corresponding
      to splicing signals (splice sites, branch points, ESE, and ESS) but also to
      predict the impact of mutations on these signals. We now need to address the
      impact of mutations that affect the splicing process, as their consequences could
      vary from the activation of cryptic signals to the skipping of one or multiple
      exons. Despite the major developments of the bioinformatics field coupled to
      experimental data generated on splicing, it is today still not possible to
      efficiently predict the consequences of mutations impacting splicing signals,
      especially to predict if they will lead to exon skipping or to cryptic splice
      site activation.

PMID- 22454053
TI  - Minigenes to confirm exon skipping mutations.
AB  - Although several bioinformatic tools exist to predict the effect on splicing of a
      nucleotide change, experimental verification with minigenes is essential for
      diagnostic purposes, as well as for revealing disease mechanisms and monitoring
      therapeutic interventions. Minigenes are splice reporter vectors (also known as
      exon-trapping vectors) that allow confirmation of the effect of mutations on the
      splicing process, indicated when patients' samples for RNA studies are not
      available. The minigene vector codes for exonic portions of a gene defined by
      functional 5' splice donor and 3' splice acceptor sites separated by intronic
      sequences where a polylinker is located. Here, the exon carrying the mutation
      under study is cloned along with its flanking intronic sequence. The resulting
      construct, in its wild-type and mutant sequence version, is transfected in
      established cell lines and the vector splicing pattern is analyzed. Ideally, the
      wild-type minigene results in correct exon inclusion, while the mutant construct
      results in exon skipping or other aberrant transcripts.

PMID- 22454054
TI  - Analysis and interpretation of RNA splicing alterations in genes involved in
      genetic disorders.
AB  - Germ line mutations in genes involved in hereditary cancer syndromes, such as
      BRCA1 and BRCA2 in breast cancer and MSH2, MSH6, MLH1, and PSM2 in hereditary
      nonpolyposis colorectal cancer (HNPCC, more recently indicated as Lynch
      syndrome), confer a high risk to develop cancer. Mutation analysis in these genes
      has resulted in the identification of a large number of sequence variants, of
      which mutations causing frame shifts and nonsense codons are considered
      undoubtedly to be pathogenic. Many variants, however, cannot be classified as
      either disease-causing mutations or neutral variants and are therefore called
      unclassified variants (UVs). A subset of these variants may have an effect on RNA
      splicing. Appropriate RNA analysis will enable the characterization of the exact
      molecular nature of this effect and hence, is essential to determine the clinical
      relevance of the genomic variant. This chapter describes the design and
      implementation of RNA analysis as an indispensible tool in today's clinical
      diagnostic setting.

PMID- 22454055
TI  - Exon skipping mutations in neurofibromatosis.
AB  - Defects at the level of pre-mRNA splicing represent a common source of disease
      mutations in almost all known diseases with a genetic aetiology. In general, it
      is commonly accepted that 15% of all pathogenic mutations are caused by splicing
      defects. However, this is probably a conservative estimate since clinical
      practice has only recently begun to routinely assess for this types of
      abnormalities. Therefore, it is expected that many currently unclassified or
      apparently harmless genetic variants will really turn out to be splicing
      affecting defects. It is also well known that some genes are more susceptible
      than others to alterations in their splicing processes. Among these genes, one of
      the most representative is the NF-1 gene. In this gene, almost 50% of all
      reported disease-causing mutations can be directly attributed to alterations of
      the pre-mRNA process. In this chapter, we review the splicing process of the NF-1
      gene and the most commonly used methods to identify splicing alterations. In
      particular, we provide practical notes on how to perform this analysis to
      maximize the chance of correctly identifying aberrant pre-mRNA splicing events in
      this gene.

PMID- 22454056
TI  - Overview on applications of antisense-mediated exon skipping.
AB  - Antisense-mediated exon skipping has multiple therapeutic applications. This
      chapter gives an overview of how this tool has been employed to restore normal
      splicing for cryptic splicing mutations, to switch between alternative splicing
      isoforms, to induce exon inclusion, to correct the reading frame to allow the
      production of internally deleted proteins, or to induce reading frame disruptions
      to achieve partial protein knockdown. For each application, examples are
      discussed and the current state of the art is described.

PMID- 22454057
TI  - Overview on DMD exon skipping.
AB  - Antisense-mediated exon skipping to restore the disrupted dystrophin reading
      frame is currently in clinical trials for Duchenne muscular dystrophy. This
      chapter describes the rationale of this approach and gives an overview of in
      vitro and in vivo experiments with antisense oligonucleotides and antisense
      genes. Finally, an overview of clinical trials is given and outstanding questions
      and hurdles are discussed.

PMID- 22454058
TI  - Overview on AON design.
AB  - Antisense-mediated exon skipping is an attractive tool to study gene function as
      well as a promising therapeutic application for a number of diseases. In order
      for antisense oligonucleotides (AONs) to induce effective exon skipping during
      pre-mRNA splicing, they have to fulfill certain criteria. These include
      resistance against endo- and exonucleases and RNase H-induced cleavage and
      suitable thermodynamic properties. Furthermore, the AON-target sequence needs to
      be accessible and should contain sequence motives that are essential for proper
      inclusion of the exon into the mRNA. For most genes, only a few AONs have been
      designed, with the exception of the DMD gene, for which over 400 AONs targeting
      the majority of DMD exons have been reported. This allows retrospective analysis
      of effective and ineffective AONs to obtain guidelines to optimize future AON
      design.

PMID- 22454059
TI  - Optimizing RNA/ENA chimeric antisense oligonucleotides using in vitro splicing.
AB  - A molecular therapy for Duchenne muscular dystrophy (DMD) that converts
      dystrophin mRNA from out-of-frame to in-frame transcripts by inducing exon
      skipping with antisense oligonucleotides (AOs) is now approaching clinical
      application. To exploit the broad therapeutic applicability of exon skipping
      therapy, it is necessary to identify AOs that are able to induce efficient and
      specific exon skipping. To optimize AOs, we have established an in vitro splicing
      system using cultured DMD myocytes. Here, we describe the process of identifying
      the best AO.Cultured DMD myocytes are established from a biopsy sample and the
      target exon is chosen. A series of AOs are designed to cover the whole target
      exon sequence. As AOs, we use 15-20-mer chimeric oligonucleotides consisting of
      2'-O-methyl RNA and modified nucleic acid (2'-O, 4'-C-ethylene-bridged nucleic
      acid). Each AO is transfected individually into cultured DMD myocytes, and the
      resulting mRNA is analyzed by reverse transcription-PCR. The ability of each AO
      to induce exon skipping is examined by comparing the amount of cDNA with and
      without exon skipping. If necessary, having roughly localized the target region,
      another set of AOs are designed and the exon skipping abilities of the new AOs
      are examined. Finally, one AO is determined as the best for the molecular
      therapy.Our simple and reliable methods using an in vitro splicing system have
      enabled us to identify optimized AOs against many exons of the DMD gene.

PMID- 22454060
TI  - Optimizing antisense oligonucleotides using phosphorodiamidate morpholino
      oligomers.
AB  - Duchenne muscular dystrophy (DMD) is caused by mutations that disrupt the reading
      frame of the human DMD gene. Selective removal of exons flanking an out-of-frame
      DMD mutation can result in an in-frame mRNA transcript that may be translated
      into an internally deleted Becker muscular dystrophy-like functionally active
      dystrophin protein with therapeutic activity. Antisense oligonucleotides (AOs)
      can be designed to bind to complementary sequences in the targeted mRNA and
      modify pre-mRNA splicing to correct the reading frame of a mutated transcript. AO
      induced exon skipping resulting in functional truncated dystrophin has been
      demonstrated in animal models of DMD both in vitro and in vivo, in DMD patient
      cells in vitro in culture, and in DMD muscle explants. The recent advances made
      in this field suggest that it is likely that AO-induced exon skipping will be the
      first gene therapy for DMD to reach the clinic. However, it should be noted that
      personalized molecular medicine may be necessary, since the various reading frame
      disrupting mutations are spread across the DMD gene. The different deletions that
      cause DMD would require skipping of different exons, which would require the
      optimization and clinical trial workup of many specific AOs. This chapter
      describes the methodologies available for the optimization of AOs, in particular
      phosphorodiamidate morpholino oligomers, for the targeted skipping of specific
      exons on the DMD gene.

PMID- 22454061
TI  - Optimizing splice-switching oligomer sequences using 2'-O-methyl phosphorothioate
      chemistry.
AB  - We have taken an empirical approach in designing splice-switching oligomers to
      induce targeted dystrophin exon skipping. The nucleotide sequence of the exon
      under examination is first analyzed for potential exon recognition motifs and
      then a set of oligomers complementary to the acceptor and donor splice sites, as
      well as intra-exonic regions predicted to contain exon splice enhancers, are
      designed and synthesized as 2'-O-methyl-modified bases on a phosphorothioate
      backbone (2OMeAOs). The 2OMeAOs can be readily transfected into cultured normal
      myogenic cells as cationic lipoplexes, and are incubated for 24 h before total
      RNA extraction and subsequent analysis by semi-quantitative RT-PCR. The
      amplification conditions used for each dystrophin transcript region under
      investigation minimize preferential production of shorter amplicons and do not
      exaggerate the level of induced RT-PCR products, compared to the endogenous
      dystrophin transcript product. It is imperative that the test oligomers are
      transfected over a range of concentrations and that the target exon is excised in
      a reproducible and dose-dependent manner.Once it has been demonstrated that an
      oligomer can induce some degree of exon skipping, that target region of the pre
      mRNA is assumed to be involved in splicing of the exon. A series of overlapping
      oligomers are prepared and evaluated by transfection into normal myogenic cells
      at lower concentrations to identify the more effective compounds. Clinical
      application requires antisense compounds that efficiently modulate splicing at
      low dosages, delivering the greatest benefits in terms of efficacy, safety, and
      cost.

PMID- 22454062
TI  - Exon skipping quantification by real-time PCR.
AB  - Antisense oligonucleotide (AON)-mediated exon skipping is a therapeutic approach
      for subsets of Duchenne muscular dystrophy (DMD) patients to ameliorate the
      severe DMD phenotype. Several groups have successfully induced exon skipping by
      AONs to reframe the mRNA in various patients carrying deletions, and phase I/II
      clinical trials are ongoing. The approach is based on targeting specific splicing
      motifs, both exonic and located on the exon borders, thus interfering with the
      spliceosome assembly by steric hindrance. Evaluation of the effectiveness of
      treatment with AONs in cells, animal models, and humans requires a sensitive,
      specific, and highly reproducible method. We have developed a real-time PCR-based
      protocol that uses the probe-based approach to recognize specific sequences
      internal to the target exon (exon-specific real-time assay). The methods for this
      protocol are described in this chapter.

PMID- 22454063
TI  - Antisense-mediated exon skipping to shift alternative splicing to treat cancer.
AB  - Manipulation of alternative splicing is a unique way of regulating gene
      expression. Here, a detailed protocol is presented for modification of HER2 pre
      mRNA alternative splicing. A 20-mer splice switching oligonucleotide (SSO)
      targeting exon 15 in HER2 pre-mRNA induced skipping of exon 15, resulted in
      significant downregulation of full-length HER2 mRNA and protein expression in
      HER2-overexpressing breast cancer cell line SK-BR-3.

PMID- 22454064
TI  - Antisense-mediated exon skipping to generate soluble receptors.
AB  - Soluble receptors modify the biological response to ligand by competing with
      their membrane-bound counterparts for the ligand. They act as competitive
      inhibitors of the signaling by binding to ligands without inducing cellular
      signal transduction pathways and thus neutralizing the bioactivity of the ligand.
      Shifting of transmembrane receptors to their soluble isoforms can be manipulated
      by using antisense oligonucleotide (AON) mediated exon skipping by targeting the
      exons which encode the transmembrane region and deleting them from the mature
      transcript. It has been shown that membrane bound receptors of cytokines TNF
      alpha and IL-5 can be successfully converted into soluble forms by AON mediated
      exon skipping. This approach can be applied for the treatment of other
      inflammatory diseases or conditions where cytokines play important role by
      favoring the expression of soluble cytokine receptors inhibiting proinflammatory
      pathways. With this strategy, decrease in mRNA and protein levels of membrane
      bound receptors upon AON treatment can be tested in vitro and in vivo by using
      the techniques mentioned in this chapter. The efficacy of AONs in producing
      therapeutic isoforms of the receptors should be tested further in vivo on disease
      models.

PMID- 22454065
TI  - Antisense-mediated exon skipping to reframe transcripts.
AB  - Numerous genetic disorders are caused by loss-of-function mutations that disrupt
      the open reading frame of the gene either by nonsense or by frameshift
      (insertion, deletion, indel, or splicing) mutations. Most of the time, the result
      is the absence of functional protein synthesis due to mRNA degradation by
      nonsense-mediated mRNA decay, or rapid degradation of a truncated protein.
      Antisense-based splicing modulation is a powerful tool that has the potential to
      treat genetic disorders by restoring the open reading frame through selective
      removal of the mutated exon, or by restoring correct splicing.We have developed
      this approach for a severe genetic skin disorder, recessive dystrophic
      epidermolysis bullosa, caused by mutations in the COL7A1 gene encoding type VII
      collagen. This gene is particularly suited for exon-skipping approaches due to
      its unique genomic structure. It is composed of 118 exons, 83 of which are in
      frame. Moreover, these exons encode a single repetitive collagenous domain.Using
      this gene as an example, we describe general methods that demonstrate the
      feasibility and efficacy of the antisense-mediated exon-skipping strategy to
      reframe transcripts.

PMID- 22454066
TI  - U1 snRNA as an effective vector for stable expression of antisense molecules and
      for the inhibition of the splicing reaction.
AB  - We report the use of the U1 snRNA as a vector for the stable expression of
      antisense molecules against the splice junctions of specific dystrophin exons.
      The single-stranded 5' terminus of U1 can be replaced by unrelated sequences as
      long as 50 nucleotides without affecting both the stability and the ability to
      assemble into snRNP particles. Effective exon skipping has been obtained for
      different dystrophin exons by antisense sequences against 5' and 3' splice sites
      alone or in combination with ESE sequences. The efficacy of these molecules has
      been studied both in in vitro systems and in animals. In both cases the chimeric
      molecules, delivered as part of lentiviral or AAV vectors (De Angelis et al. Proc
      Natl Acad Sci USA 99:9456-9461, 2002; Denti et al. Proc Natl Acad Sci USA 103:
      3758-3763, 2006; Denti et al. Hum Gene Ther 17: 565-743, 2006; Denti et al. Hum
      Gene Ther 19: 601-608, 2008; Incitti et al. Mol Ther 18: 1675-1682, 2010),
      provided high skipping activity and efficient rescue of dystrophin synthesis.
      Moreover, the U1-antisense molecules, delivered to mice via systemic injection of
      recombinant AAV viruses, displayed body wide transduction, long-term expression,
      dystrophin rescue as well as morphological and functional benefit (Denti et al.
      Hum Gene Ther 19: 601-608, 2008). In this Chapter we report methods for producing
      U1-antisense expression cassettes in the backbone of lentiviral constructs and
      for testing their activity both in patients' derived myoblasts as well as in
      fibroblasts reprogrammed to muscle differentiation.

PMID- 22454067
TI  - Engineering U7snRNA gene to reframe transcripts.
AB  - Antisense-mediated splicing modulation of premessenger RNA represents a novel
      therapeutic strategy for several types of pathologies such as genetic disorders,
      cancers, and infectious diseases. Antisense oligonucleotides designed to bind to
      specific mRNA molecules have been actively developed for more than 20 years as a
      form of molecular medicine to modulate splicing patterns or inhibit protein
      translation. More recently, small nuclear RNA such as U7 or U1 small nuclear RNA
      have been used to carry antisense sequences, offering the advantage of long-term
      effect when delivered to cells using viral vectors. We have previously
      demonstrated the therapeutic potential of U7snRNA targeting dystrophin mRNA as a
      treatment for Duchenne muscular dystrophy. In particular, we showed that
      bifunctional U7 snRNAs harboring silencer motifs induce complete skipping of exon
      51, and thus restore dystrophin expression in DMD patients cells to near wild
      type levels. These new constructs are very promising for the optimization of
      therapeutic exon skipping for DMD, but also offer powerful and versatile tools to
      modulate pre-mRNA splicing in a wide range of applications. Here, we outline the
      design of these U7snRNA constructs to achieve efficient exon-skipping and
      describe methods to evaluate the efficacy of such U7snRNA constructs in vitro
      using the dystrophin gene as an example.

PMID- 22454068
TI  - Dynamic fluorescent and luminescent reporters for cell-based splicing screens.
AB  - Alternative splicing of pre-mRNA transcripts is a critical and extensively
      utilized mechanism of gene regulation. In this chapter, we describe a series of
      fluorescent and luminescent minigene reporters our lab has used to facilitate the
      study of alternative splicing regulation in cultured cells. Through the use of
      different versions of these minigenes, the inclusion level of a cassette exon can
      be directly ascertained by fluorescence or luciferase activity, thereby making it
      possible to establish cell-based assays for induced exon splicing or skipping. A
      successful application of these minigenes in a high-throughput cDNA screen led to
      the identification of a cell type-specific regulator of FGFR2 splicing,
      illustrating the power of these reporters to yield novel insights into
      alternative splicing. The methods and minigenes described are adaptable for
      genetic screens to uncover novel regulators of a broader set of alternative
      splicing events in other gene transcripts. These reporters also have a dynamic
      range that is suitable for small molecule screening for compounds that can
      regulate splicing.

PMID- 22454069
TI  - Antisense-mediated exon-skipping to induce gene knockdown.
AB  - Exon-skipping antisense oligonucleotides (ASOs) can be used to knockdown the
      expression of an undesired gene or specific gene isoform. This chapter discusses
      the potential therapeutic applications of the technique and provides a sample
      protocol for inducing exon-skipping in Apolipoprotein B in vitro, as well as a
      protocol for quantifying exon-skipping using real-time PCR.

PMID- 22454070
TI  - Antisense-mediated exon inclusion.
AB  - Exon skipping induced by gene mutations is a common mechanism responsible for
      many genetic diseases. A practical approach to correct the aberrant splicing of
      defective genes is to use antisense oligonucleotides (ASOs). The recognition of
      splice sites and the regulation of splicing involve multiple positive or negative
      cis-acting elements and trans-acting factors. Base-pairing of ASOs to a negative
      element in a targeted pre-mRNA blocks the binding of splicing repressors to this
      cis-element and/or disrupts an unfavorable secondary structure; as a result, the
      ASO restores exon inclusion. For example, we have recently shown that appropriate
      2'-O-(2-methoxyethyl) (MOE) phosphorothioate-modified ASOs can efficiently
      correct survival motor neuron 2 (SMN2) exon 7 splicing in a cell-free splicing
      assay, in cultured human cells-including patient fibroblasts-and in both
      peripheral tissues and the CNS of SMA mouse models. These ASOs are promising drug
      leads for SMA therapy.

PMID- 22454071
TI  - Antisense genes to induce exon inclusion.
AB  - Many inherited diseases are associated with changed splicing patterns, and
      alternative splicing influences several biological processes as well as the
      replication of certain viral pathogens. For this reason, there is a broad
      interest in modulating individual splicing events for therapeutic purposes. Based
      on the small nuclear RNA (snRNA) U7, we have developed expression vectors for
      short antisense RNAs that accumulate in the cell nucleus where splicing occurs
      and that can very specifically modulate the splicing of individual exons. More
      specifically, in the context of the fatal neuromuscular disorder Spinal Muscular
      Atrophy (SMA), we have shown that U7 snRNA constructs can restore the inclusion
      of exon 7 in the SMN2 gene and thereby alleviate or even fully cure disease
      symptoms in a severe mouse model for SMA. Here we describe more generally
      procedures to produce U7 constructs to induce exon inclusion and to test their
      efficiency in cell culture experiments at the level of RNA as well as protein.
      The analytical methods comprise reverse transcription (RT-)PCR to detect the
      splicing changes, quantitative real-time RT-PCR to measure U7 snRNA expression
      levels and western blot and immunofluorescence methods to detect a restoration of
      protein expression. Additionally, we indicate how U7 cassettes can be introduced
      into gene transfer vectors for in vivo experiments in animal models or to
      transduce cell systems that are not readily amenable to DNA transfection.

PMID- 22454072
TI  - Using mini-genes to identify factors that modulate alternative splicing.
AB  - Many genetic mutations result in the disruption of (alternative) splicing. Prime
      examples are the SMN1 and SMN2 genes: a silent mutation in SMN2 leads to the
      skipping of the constitutive exon 7 in the majority of SMN2 transcripts, while
      this exon is generally included in SMN1 transcripts. Lack of SMN is embryonic
      lethal and loss of SMN1 genes leads to a severe decrease in SMN protein and is
      associated with spinal muscular atrophy. There are proteins and drugs that can
      chance alternative splicing events, e.g. increase the inclusion of exon 7 in
      SMN2. This chapter describes mini-genes and methods that can be employed to
      screen for candidate proteins and drugs.

PMID- 22454073
TI  - Overview of alternative oligonucleotide chemistries for exon skipping.
AB  - The chemistry of the oligonucleotide backbone is crucial to obtaining high
      activity in vivo in exon skipping applications. Apart from the ability to bind
      strongly and sequence-specifically to pre-mRNA targets, the type of backbone also
      influences cell delivery, in vivo pharmacology, bio-distribution, toxicology, and
      ultimately the therapeutic use in humans. Reviewed here are classes of
      oligonucleotide commonly used for exon skipping applications, namely negatively
      charged backbones typified by RNA analogues having 2'-O-substitution and a
      phosphorothioate linkage and charge-neutral backbones such as PNA and PMO. Also
      discussed are peptide conjugates of PNA and PMO that enhance cellular and in vivo
      delivery and their potential for drug development. Finally, the prospects for
      development of other analogue types in exon skipping applications are outlined.

PMID- 22454074
TI  - Identification of peptides for tissue-specific delivery.
AB  - Antisense-mediated exon skipping has shown to be a promising therapeutic approach
      and is in clinical trials for Duchenne muscular dystrophy. However, after
      systemic treatment the majority of the injected antisense oligonucleotides (AONs)
      will not end up in the intended tissue. This mistargeting of AONs might have
      detrimental effects, especially with long-term treatment and continuous
      accumulation of AONs. Further, even when no detrimental effects occur,
      mistargeted AONs are lost for exon skipping in the intended tissue. One way to
      reduce the amount of mistargeted AONs is by adding a peptide that specifically
      binds to and is taken up by the intended tissue. Such peptides can be found by
      screening phage display libraries. With in silico, in vitro, and in vivo testing,
      the peptides that bind the intended tissue most efficiently and most specifically
      can be identified.

PMID- 22454075
TI  - Systemic delivery of antisense oligomer in animal models and its implications for
      treating DMD.
AB  - Antisense oligomer (AO)-mediated splicing modulation for treating DMD demands a
      systemic administration of AOs as pharmacological drugs to achieve effective
      prevention of disease progression and to improve quality and longevity of patient
      life. Three routes, namely, intravenous injection (IV), intraperitoneal injection
      (IP), and subcutaneous injections (SC), of systemic delivery of AOs have been
      examined in animal models, and two of them, IV and SC, are being applied in the
      ongoing clinical trials. The main barrier for systemic treatment with unmodified
      AO of both chemistries, 2'-O methyl Phosphorothioate RNA and phosphorodiamidate
      morpholino, is the high degree of variation in exon skipping efficiency both
      between body-wide muscles and within individual muscle seen in mouse models. AO
      therapy will likely critically depend on adequate dosing regimens to achieve
      therapeutic effect.

PMID- 22454076
TI  - Cell-penetrating peptides enhance systemic delivery of antisense morpholino
      oligomers.
AB  - Exon-skipping efficacy of phosphorodiamidate morpholino oligomers (Morpholinos)
      has been demonstrated in a proof-of-concept clinical trial for Duchenne muscular
      dystrophy (DMD). Systemic delivery of Morpholinos can be significantly enhanced
      by conjugating them to cell-penetrating peptides. The improved efficacy has been
      demonstrated in DMD animal models, including mdx mice and utrophin-dystrophin
      double-knockout mice. Compared to unconjugated Morpholinos, far lower doses of
      the -peptide-Morpholino conjugates can restore dystrophin sufficiently to reduce
      disease pathology, increase skeletal and cardiac muscle functions and prolong
      survival of animals. In addition, the conjugates enter cardiomyocytes in useful
      quantities and improve heart functions. Here, an experimental protocol for making
      Tat peptide-Morpholino conjugate is described.

PMID- 22454077
TI  - Optimizing tissue-specific antisense oligonucleotide-peptide conjugates.
AB  - Cell-targeting peptides which improve tissue-specific delivery of antisense
      oligonucleotides (AONs) are a new exciting "next-generation" potential AON
      therapy. New peptides are regularly developed which increase targeting and cell
      penetration for the AON treatment of mRNA misregulated diseases. Optimization of
      these peptide conjugate AONs requires systematic treatment and methods of
      analysis. This chapter describes methods for analyzing cell-targeting peptide
      conjugated AONs in primary cultured cell lines and for local and systemic
      delivery to the mouse for the treatment of Duchenne muscular dystrophy (DMD).
      Chimeric and novel cell-penetrating peptides have already been described to
      induce high levels of exon skipping and dystrophin protein expression in tissues
      body-wide at very low doses of AON. Screening of future novel peptides may be
      achieved by preliminary in vitro screening followed by in vivo administration of
      the most promising peptide-conjugated AONs. Physiological and functional
      correction of dystrophin protein may be confirmed by a number of techniques as
      described and allows for the fast-tracking of candidate peptides to drug trial
      for DMD.

PMID- 22454078
TI  - Use of aspirin postdiagnosis improves survival for colon cancer patients.
AB  - BACKGROUND: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs)
      and aspirin, in particular, on colorectal cancer is well established. More
      recently, it has been suggested that aspirin may also have a therapeutic role.
      Aim of the present observational population-based study was to assess the
      therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment
      used after the diagnosis of colorectal cancer patients. METHODS: Data concerning
      prescriptions were obtained from PHARMO record linkage systems and all patients
      diagnosed with colorectal cancer (1998-2007) were selected from the Eindhoven
      Cancer Registry (population-based cancer registry). Aspirin/NSAID use was
      classified as none, prediagnosis and postdiagnosis and only postdiagnosis.
      Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of
      the colorectal cancer to the date of first use of aspirin or NSAIDs and user from
      first use to the end of follow-up. Poisson regression was performed with user
      status as time-varying exposure. RESULTS: In total, 1176 (26%) patients were non
      users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were
      only postdiagnosis users (total n=4481). Compared with non-users, a survival gain
      was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95%
      confidence interval (CI) 0.63-0.95; P=0.015). Stratified for colon and rectal,
      the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50
      0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61
      (95%CI 0.46-0.81; P=0.001). In rectal cancer, aspirin use was not associated with
      survival (adjusted RR 1.10 (95%CI 0.79-1.54; P=0.6). The NSAIDs use was
      associated with decreased survival (adjusted RR 1.93 (95%CI 1.70-2.20; P<0.001).
      CONCLUSION: Aspirin use initiated or continued after diagnosis of colon cancer is
      associated with a lower risk of overall mortality. These findings strongly
      support initiation of a placebo-controlled trial that investigates the role of
      aspirin as adjuvant treatment in colon cancer patients.

PMID- 22454079
TI  - Comparison and combination of blood-based inflammatory markers with faecal occult
      blood tests for non-invasive colorectal cancer screening.
AB  - BACKGROUND: Faecal occult blood tests (FOBTs) are widely used for colorectal
      cancer (CRC) screening. Blood-based inflammatory markers have been suggested as
      alternative or supplementary non-invasive CRC screening tests. METHODS: Among 179
      CRC patients, 193 people with advanced adenoma and 225 people free of neoplasm, C
      reactive protein (CRP), serum CD26 (sCD26), complement C3a anaphylatoxin and
      tissue inhibitor of metalloproteinases 1 (TIMP-1) levels in blood were measured
      by ELISA tests, and an immunochemical FOBT (iFOBT) and a guaiac-based FOBT were
      performed. Receiver operating characteristic curves were constructed and the
      areas under the curves (AUCs) were compared. RESULTS: The blood levels of CRP,
      sCD26 and TIMP-1 showed statistically significant differences between CRC
      patients and neoplasm-free participants, and levels of TIMP-1 were furthermore
      significantly elevated in advanced adenoma patients. For the four inflammatory
      markers, AUCs ranged from 0.52 to 0.62 for CRC detection and from 0.50 to 0.58
      for advanced adenomas detection, compared with AUCs of 0.90 and 0.68 for the
      iFOBT. At 97% specificity, blood markers showed much lower sensitivities than
      FOBTs. Combining inflammatory markers with the iFOBT increased the AUC for
      advanced adenomas. CONCLUSION: These blood-based markers do not seem to be an
      alternative to FOBT-based CRC screening. The potential use of these and other
      blood-based tests in combination with iFOBT might deserve further attention.

PMID- 22454080
TI  - NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with
      metastatic site specificity.
AB  - BACKGROUND: Novel prognostic biomarkers and therapeutic strategies are urgently
      required for malignant melanoma. Ecto-5-prime-nucleotidase (NT5E; CD73)
      overexpression has been reported in several human cancers. The mechanism(s)
      underlying deregulated expression and the clinical consequences of changes in
      expression are not known. METHODS: We used RT-PCR, qPCR, methylation-specific PCR
      and pyrosequencing to analyse expression and regulation of NT5E in malignant
      melanoma cell lines and primary and metastatic melanomas. RESULTS: NT5E is
      subject to epigenetic regulation in melanoma. NT5E mRNA is downregulated by
      methylation-dependent transcriptional silencing in the melanoma cell lines
      SKMel2, SKMel23, WM35, Mel501, Mel505 and C81-61 and expression is reactivated by
      azacytidine. In contrast, the CpG island is unmethylated and the gene expressed
      in cultured normal melanocytes. In clinical cases of melanoma, methylation in the
      NT5E CpG island occurs in both primary and metastatic melanomas and correlates
      with transcriptional downregulation of NT5E mRNA. Relapse with metastatic
      disease, particularly to the visceral sites and brain, is more common in primary
      melanomas lacking NT5E methylation. Primary melanomas with methylation in NT5E
      show limited metastatic potential or more commonly metastasise predominantly to
      nodal sites rather than viscera and brain (P=0.01). CONCLUSION: Deregulation of
      NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island.
      Confirmation of our results in larger clinical series would support the candidacy
      of NT5E as a clinical biomarker in melanoma, which could be applied in both
      primary and relapsed disease. Inhibition of NT5E may have therapeutic potential
      in melanoma, particularly in patients with more aggressive disease metastatic to
      viscera or the brain.

PMID- 22454082
TI  - Nutmeg liver and ascites resulting from a membranous web obstruction at the
      hepatic origin of the inferior vena cava.

PMID- 22454083
TI  - Greater binding affinity of trivalent antimony to a CCCH zinc finger domain
      compared to a CCHC domain of kinetoplastid proteins.
AB  - It has been reported recently that Sb(III) competes with Zn(II) for its binding
      to the CCHC zinc finger domain of the HIV-1 NCp7 protein, suggesting that zinc
      finger proteins may be molecular targets for antimony-based drugs. Here, the
      interaction of Sb(III) with a CCCH zinc finger domain, which is considered to
      play a crucial role in the biology of kinetoplastid protozoa, has been
      characterized for the first time. The binding characteristics of Sb(III) were
      compared between a CCCH-type peptide derived from a kinetoplastid protein and two
      different CCHC-type zinc finger peptides. The formation of 1 : 1 Zn-peptide and
      Sb-peptide complexes from the different peptides was demonstrated using circular
      dichroism, UV absorption, fluorescence spectroscopies and ESI-MS. Titration of
      the Zn-peptide complexes with SbCl(3) was performed at pH 6 and 7, exploiting the
      intrinsic fluorescence of the peptides. The differential spectral characteristics
      of the peptides allowed for competition experiments between the different
      peptides for binding of Zn(II). The present study establishes that Sb(III) more
      effectively displaces Zn(II) from the CCCH peptide than CCHC ones, as a result of
      both the greater stability of the Sb-CCCH complex (compared to Sb-CCHC complexes)
      and the lower stability of the Zn-CCCH complex (compared to Zn-CCHC complexes).
      Comparison of the binding characteristics of Sb(III) or Zn(II) between the CCHC
      type peptides with different amino acid sequences supports the model that not
      only the conserved zinc finger motif, but also the sequence of non-conserved
      amino acids determines the binding affinity of Sb(III) and Zn(II). These data
      suggest that the interaction of Sb(III) with CCCH-type zinc finger proteins may
      modulate, or even mediate, the pharmacological action of antimonial drugs.

PMID- 22454081
TI  - Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway
      are related with trastuzumab resistance in HER2 breast carcinomas.
AB  - BACKGROUND: Trastuzumab resistance hampers its well-known efficacy to control
      HER2-positive breast cancer. The involvement of PI3K/Akt pathway in this
      mechanism is still not definitively confirmed. METHODS: We selected 155 patients
      treated with trastuzumab after development of metastasis or as
      adjuvant/neoadjuvant therapy. We performed immunohistochemistry for HER2, ER/PR,
      epidermal growth factor 1-receptor (EGFR), alpha-insulin-like growth factor 1
      receptor (IGF1R), phosphatase and tensin homologue (PTEN), p110alpha, pAkt, pBad,
      pmTOR, pMAPK, MUC1, Ki67, p53 and p27; mutational analysis of PIK3CA and PTEN,
      and PTEN promoter hypermethylation. RESULTS: We found 46% ER/PR-positive tumours,
      overexpression of EGFR (15%), alpha-IGF1R (25%), p110alpha (19%), pAkt (28%),
      pBad (22%), pmTOR (23%), pMAPK (24%), MUC1 (80%), PTEN loss (20%), and PTEN
      promoter hypermethylation (20%). PIK3CA and PTEN mutations were detected in 17%
      and 26% tumours, respectively. Patients receiving adjuvant trastuzumab with alpha
      IGF1R or pBad overexpressing tumours presented shorter progression-free survival
      (PFS) (all P<=0.043). Also, p110alpha and mTOR overexpression, liver and brain
      relapses implied poor overall survival (OS) (all P<=0.041). In patients with
      metastatic disease, decreased PFS correlated with p110alpha expression (P=0.024),
      whereas for OS were the presence of vascular invasion and EGFR expression
      (P<=0.019; Cox analysis). CONCLUSION: Our results support that trastuzumab
      resistance mechanisms are related with deregulation of PTEN/PI3K/Akt/mTOR
      pathway, and/or EGFR and IGF1R overexpression in a subset of HER2-positive breast
      carcinomas.

PMID- 22454084
TI  - A critical assessment of the specific role of microwave irradiation in the
      synthesis of ZnO micro- and nanostructured materials.
AB  - A rapid, microwave-assisted hydrothermal method has been developed to access
      ultrafine ZnO hexagonal microrods of about 3-4 MUm in length and 200-300 nm in
      width by using a 1:5 zinc nitrate/urea precursor system. The size and morphology
      of these ZnO materials can be influenced by subtle changes in precursor
      concentration, solvent system, and reaction temperature. Optimized conditions
      involve the use of a 1:3 water/ethylene glycol solvent system and 10 min
      microwave heating at 150  degrees C in a dedicated single-mode microwave reactor
      with internal temperature control. Carefully executed control experiments
      ensuring identical heating and cooling profiles, stirring rates, and reactor
      geometries have demonstrated that for these preparations of ZnO microrods no
      differences between conventional and microwave dielectric heating are observed.
      The resulting ZnO microrods exhibited the same crystal phase, primary crystallite
      size, shape, and size distribution regardless of the heating mode. Similar
      results were obtained for the ultrafast preparation of ZnO nanoparticles with
      diameters of approximately 20 nm, synthesized by means of a nonaqueous sol-gel
      process at 200  degrees C from a Zn(acac)(2) (acac=acetylacetonate) precursor in
      benzyl alcohol. The specific role of microwave irradiation in enhancing these
      nanomaterial syntheses can thus be attributed to a purely thermal effect as a
      result of higher reaction temperatures, more rapid heating, and a better control
      of process parameters.

PMID- 22454085
TI  - Carnosine and cancer: a perspective.
AB  - The application of carnosine in medicine has been discussed since several years,
      but many claims of therapeutic effects have not been substantiated by rigorous
      experimental examination. In the present perspective, a possible use of carnosine
      as an anti-neoplastic therapeutic, especially for the treatment of malignant
      brain tumours such as glioblastoma is discussed. Possible mechanisms by which
      carnosine may perform its anti-tumourigenic effects are outlined and its expected
      bioavailability and possible negative and positive side effects are considered.
      Finally, alternative strategies are examined such as treatment with other
      dipeptides or beta-alanine.

PMID- 22454086
TI  - beta-Peptoids: synthesis of a novel dimer having a fully extended conformation.
AB  - Chiral imines 1a,b, already synthesized in our laboratory, were converted in good
      yield by reduction into the corresponding N-benzyl-gamma-lactams 2a,b.
      Desilylation followed by oxidation of the hydroxymethyl functionality gave the N
      benzyl-beta-amino acids 5a,b in good yield and high purity. Starting from
      compound 6a, the corresponding beta-peptoid dimer 8 was prepared, together with
      its derivatives 9 and 10, these latter displaying conformational restriction
      about the peptide bond, as evidenced by NMR data.

PMID- 22454087
TI  - Mechanism-based pharmacokinetic/pharmacodynamic modeling of rat prefrontal
      cortical dopamine response to dual acting norepinephrine reuptake inhibitor and 5
      HT1A partial agonist.
AB  - Evidence suggests that compounds possessing both norepinephrine reuptake
      inhibition and 5-HT(1A) partial agonism (NRI/5-HT(1A)) activities may have a
      greater efficacy in treating neuropsychiatric disorders than compounds possessing
      either activity alone. The objectives of the present study were first to
      characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of the
      plasma concentrations of atomoxetine (NRI) and buspirone (5-HT(1A) partial
      agonist), administered alone and in combination, on the prefrontal cortex
      dopamine levels in rats, and second to use the model developed to characterize
      the PK/PD relationship of novel NRI/5-HT(1A) compounds, PF-04269339 and PF
      03529936, in a NRI/5-HT(1A) drug discovery program. Maximal dopamine elevation
      was twofold higher after administration of atomoxetine and buspirone in
      combination, PF-04269339, or PF-03529936 than after administration of atomoxetine
      or buspirone alone. A mechanism-based extended indirect response model
      characterized the time profiles of the prefrontal cortex dopamine response to
      atomoxetine and buspirone, administered alone or in combination. After fixing
      three mechanism-specific pharmacodynamic parameters (I (max) and gamma2 for NRI
      and gamma1 for 5-HT(1A)) based on the model for atomoxetine and/or buspirone, the
      model fitted the exposure-response profiles of PF-04269339 and PF-03529936 well.
      Good in vitro-to-in vivo correlation was demonstrated with the compound-specific
      pharmacodynamic parameters (IC(50) for NRI and SC(50) and S (max) for 5-HT(1A))
      across the compounds. In summary, a piecewise modeling approach was used
      successfully for the characterization of the PK/PD relationship of novel NRI/5
      HT(1A) compounds on prefrontal cortex dopamine levels in rats. The application
      and value of the mechanism-based modeling in the dual pharmacology drug discovery
      program are also discussed.

PMID- 22454088
TI  - Identification of blood and wound isolates of C. canimorsus and C. cynodegmi
      using VITEK2 and MALDI-TOF.
AB  - Capnocytophaga canimorsus and C. cynodegmi are gram negative bacteria that can be
      transmitted to humans from dogs or cats and cause serious infections. Routine
      bacteriological methods, including fermentation and phenotypic tests are
      insufficient to correctly identify C. canimorsus or C. cynodegmi. The aim of this
      study was to evaluate the performance of VITEK2 and MALDI-TOF in identification
      of these bacteria. Twenty two isolates that were identified as C. canimorsus / C.
      cynodegmi by 16S rRNA sequencing were included in the study and were further
      investigated with VITEK2 and MALDI-TOF. A Capnocytophaga species-specific PCR was
      used as the reference method. Out of 22 included isolates, the species-specific
      PCR identified six blood isolates as C. canimorsus and 14 wound isolates as C.
      cynodegmi. Two isolates could not be identified with the reference method. VITEK2
      identified 10/20 isolates correctly to Capnocytophaga spp. MALDI-TOF analysis
      correctly identified 6/6 C. canimorsus and 13/14 C. cynodegmi isolates. The mean
      time to identification with VITEK2 was 6 hours whereas MALDI-TOF required
      approximately 10 minutes per sample. Here we show that MALDI-TOF rapidly
      identified C. canimorsus and C. cynodegmi and thus constitutes a valuable
      diagnostic tool in the clinical laboratory.

PMID- 22454089
TI  - Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of
      women with cervical and vulvar disease: retrospective pooled analysis of trial
      data.
AB  - OBJECTIVES: To determine the effect of human papillomavirus (HPV) quadrivalent
      vaccine on the risk of developing subsequent disease after an excisional
      procedure for cervical intraepithelial neoplasia or diagnosis of genital warts,
      vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia. DESIGN:
      Retrospective analysis of data from two international, double blind, placebo
      controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013
      (FUTURE I) and protocol 015 (FUTURE II)). SETTING: Primary care centres and
      university or hospital associated health centres in 24 countries and territories
      around the world. PARTICIPANTS: Among 17,622 women aged 15-26 years who underwent
      1:1 randomisation to vaccine or placebo, 2054 received cervical surgery or were
      diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal
      intraepithelial neoplasia. INTERVENTION: Three doses of quadrivalent HPV vaccine
      or placebo at day 1, month 2, and month 6. MAIN OUTCOME MEASURES: Incidence of
      HPV related disease from 60 days after treatment or diagnosis, expressed as the
      number of women with an end point per 100 person years at risk. RESULTS: A total
      of 587 vaccine and 763 placebo recipients underwent cervical surgery. The
      incidence of any subsequent HPV related disease was 6.6 and 12.2 in vaccine and
      placebo recipients respectively (46.2% reduction (95% confidence interval 22.5%
      to 63.2%) with vaccination). Vaccination was associated with a significant
      reduction in risk of any subsequent high grade disease of the cervix by 64.9%
      (20.1% to 86.3%). A total of 229 vaccine recipients and 475 placebo recipients
      were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal
      intraepithelial neoplasia, and the incidence of any subsequent HPV related
      disease was 20.1 and 31.0 in vaccine and placebo recipients respectively (35.2%
      reduction (13.8% to 51.8%)). CONCLUSIONS: Previous vaccination with quadrivalent
      HPV vaccine among women who had surgical treatment for HPV related disease
      significantly reduced the incidence of subsequent HPV related disease, including
      high grade disease. TRIAL REGISTRATIONS: NCT00092521 and NCT00092534.

PMID- 22454090
TI  - Effect of quadrivalent HPV vaccination on HPV related disease in women treated
      for cervical or vulvar/vaginal disease.

PMID- 22454091
TI  - Risk factors for mortality from imported falciparum malaria in the United Kingdom
      over 20 years: an observational study.
AB  - OBJECTIVES: To determine which travellers with malaria are at greatest risk of
      dying, highlighting factors which can be used to target health messages to
      travellers. DESIGN: Observational study based on 20 years of UK national data.
      SETTING: National register of malaria cases. PARTICIPANTS: 25,054 patients
      notified with Plasmodium falciparum malaria, of whom 184 died, between 1987 and
      2006. MAIN OUTCOME MEASURES: Comparison between those with falciparum malaria who
      died and non-fatal cases, including age, reason for travel, country of birth,
      time of year diagnosed, malaria prophylaxis used. RESULTS: Mortality increased
      steadily with age, with a case fatality of 25/548 (4.6%) in people aged >65
      years, adjusted odds ratio 10.68 (95% confidence interval 6.4 to 17.8), P<0.001
      compared with 18-35 year olds. There were no deaths in the <= 5 year age group.
      Case fatality was 3.0% (81/2740 cases) in tourists compared with 0.32% (26/8077)
      in travellers visiting friends and relatives (adjusted odds ratio 8.2 (5.1 to
      13.3), P<0.001). Those born in African countries with endemic malaria had a case
      fatality of 0.4% (36/8937) compared with 2.4% (142/5849) in others (adjusted odds
      ratio 4.6 (3.1 to 9.9), P<0.001). Case fatality was particularly high from the
      Gambia. There was an inverse correlation in mortality between region of
      presentation and number of cases seen in the region (R(2) = 0.72, P<0.001). Most
      delay in fatal cases was in seeking care. CONCLUSIONS: Most travellers acquiring
      malaria are of African heritage visiting friends and relatives. In contrast the
      risks of dying from malaria once acquired are highest in the elderly, tourists,
      and those presenting in areas in which malaria is seldom seen. Doctors often do
      not think of these as high risk groups for malaria; for this reason they are
      important groups to target in pre-travel advice.

PMID- 22454092
TI  - Elucidation of post-PKS tailoring steps involved in landomycin biosynthesis.
AB  - The functional roles of all proposed enzymes involved in the post-PKS redox
      reactions of the biosynthesis of various landomycin aglycones were thoroughly
      studied, both in vivo and in vitro. The results revealed that LanM2 acts as a
      dehydratase and is responsible for concomitant release of the last PKS-tethered
      intermediate to yield prejadomycin (10). Prejadomycin (10) was confirmed to be a
      general pathway intermediate of the biosynthesis. Oxygenase LanE and the
      reductase LanV are sufficient to convert 10 into 11-deoxylandomycinone (5) in the
      presence of NADH. LanZ4 is a reductase providing reduced flavin (FMNH) co-factor
      to the partner enzyme LanZ5, which controls all remaining steps. LanZ5, a
      bifunctional oxygenase-dehydratase, is a key enzyme directing landomycin
      biosynthesis. It catalyzes hydroxylation at the 11-position preferentially only
      after the first glycosylation step, and requires the presence of LanZ4. In the
      absence of such a glycosylation, LanZ5 catalyzes C5,6-dehydration, leading to the
      production of anhydrolandomycinone (8) or tetrangulol (9). The overall results
      provided a revised pathway for the biosynthesis of the four aglycones that are
      found in various congeners of the landomycin group.

PMID- 22454093
TI  - Calcific myonecrosis: a two-patient case series.
AB  - Calcific myonecrosis is a rare entity with only 57 cases reported in the English
      literature to date. It is a late complication of compartment syndrome of the limb
      and results in characteristic muscle necrosis with central liquefaction and
      peripheral calcification. This series presents a further two cases and
      consolidates the diagnostic features and treatment modalities described in the
      literature.

PMID- 22454094
TI  - Assessment of particulate matter in the urban atmosphere: size distribution,
      metal composition and source characterization using principal component analysis.
AB  - In this study, the size distribution of airborne particles and related heavy
      metals Co, Cd, Sn, Cu, Ni, Cr, Pb and V in two urban areas in Istanbul: Yenibosna
      and Goztepe, were examined. The different inhalable particles were collected by
      using a cascade impactor in eight size fractions (<0.4 MUm, 0.4-0.7 MUm, 1.1-2.1
      MUm, 2.1-3.3 MUm, 3.3-4.7 MUm, 4.7-5.8 MUm, 5.8-9 MUm and >9 MUm) for six months
      at each station. Samples were collected on glass fiber filters and filters were
      extracted and analyzed using ICP-MS. Log-normal distributions showed that the
      particles collected at the Yenibosna site have a smaller size compared to the
      Goztepe samples and the size distribution of PM was represented the best by the
      tri-modal. The average total particle concentrations and standard deviations were
      obtained as 67.7 +/- 17.0 MUg m(-3) and 82.1 +/- 21.2 MUg m(-3), at the Yenibosna
      and Goztepe sites, respectively. The higher metal rate in fine and medium coarse
      PM showed that the anthropogenic sources were the most significant pollutant
      source. Principal component analysis identified five components for PM namely
      traffic, road dust, coal and fuel oil combustion, and industrial.

PMID- 22454095
TI  - [Anemia and iron deficiency in the elderly. Prevalence, diagnostics and new
      therapeutic options].
AB  - The prevalence of anemia in geriatric patients is high. With some variation in
      different patient cohorts, prevalence of anemia can reach 40%. Anemia is not an
      age-related disease on its own, but is a symptom with multifactorial genesis and
      high risk potential. It directly influences mortality, morbidity, and the rate of
      hospitalization, particularly in older patients suffering from chronic heart
      failure or chronic kidney disease. The high prevalence of anemia in chronic
      kidney disease is explained by a combination of erythropoietin and iron
      deficiency. This review summarizes the recommendations of the iron symposium at
      the 2010 German Geriatric Society Meeting in Potsdam, Germany. It intends to
      provide current information on prevalence, diagnostic work-up, and therapeutic
      options for anemia in the rapidly growing group of elderly patients.

PMID- 22454096
TI  - [Anemia in the elderly. Urgent need for guidelines].
AB  - The prevalence of anemia in the elderly is high and can reach among independent
      community-dwelling persons > 20% and among hospitalized geriatric patients up to
      40%. Anemia in the elderly has numerous causes rather than being clearly age
      related. Although it is widely acknowledged that anemia influences morbidity and
      mortality in geriatric patients in a negative manner, guidelines concerning
      diagnostics and therapeutic steps do not exist in Germany. We present a work-up
      of guidelines of German (AWMF) and international (G-I-N, NGC) specialists'
      societies dealing with the subject "anemia." Regarding the demographic changes
      with a growing population of geriatric patients with anemia, the development of a
      national (German) guideline for an ethically acceptable and cost-effective
      management of anemia in the elderly is necessary.

PMID- 22454097
TI  - Voxelwise analysis of conventional magnetic resonance imaging to predict future
      disability in early relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: The ability of conventional magnetic resonance imaging (MRI) to
      predict subsequent physical disability and cognitive deterioration after a
      clinically isolated syndrome (CIS) is weak. OBJECTIVES: We aimed to investigate
      whether conventional MRI changes over 1 year could predict cognitive and physical
      disability 5 years later in CIS. We performed analyses using a global approach
      (T(2) lesion load, number of T(2) lesions), but also a topographic approach.
      METHODS: This study included 38 patients with a CIS. At inclusion, 10 out of 38
      patients fulfilled the 2010 revised McDonald's criteria for the diagnosis of
      multiple sclerosis. Expanded Disability Status Scale (EDSS) evaluation was
      performed at baseline, year 1 and year 5, and cognitive evaluation at baseline
      and year 5. T(2)-weighted MRI was performed at baseline and year 1. We used
      voxelwise analysis to analyse the predictive value of lesions location for
      subsequent disability. RESULTS: Using the global approach, no correlation was
      found between MRI and clinical data. The occurrence or growth of new lesions in
      the brainstem was correlated with EDSS changes over the 5 years of follow-up. The
      occurrence or growth of new lesions in cerebellum, thalami, corpus callosum and
      frontal lobes over 1 year was correlated with cognitive impairment at 5 years.
      CONCLUSION: The assessment of lesion location at the first stage of multiple
      sclerosis may be of value to predict future clinical disability.

PMID- 22454098
TI  - Prediction of antibody persistency from antibody titres to natalizumab.
AB  - BACKGROUND: In a subgroup of patients with multiple sclerosis natalizumab therapy
      causes generation of anti-natalizumab antibodies that may be transient or
      persistent. It is recommended to discontinue natalizumab therapy in persistently
      antibody-positive patients. OBJECTIVE: To use titres of anti-natalizumab
      antibodies to predict persistency of antibodies. PATIENTS AND METHODS: In 525
      consecutive natalizumab treated patients tested for anti-natalizumab antibodies
      43 (8.2%) were antibody-positive. Thirty of the antibody-positive patients, who
      were tested both at three and at six months after treatment start, had antibody
      titres in blood measured using an extended ELISA method. RESULTS: Samples from
      persistently positive patients ( N =18) had higher titre values than samples from
      transiently positive patients ( N =12). A cut-off value for high titre values was
      generated, above which patients may discontinue natalizumab therapy after three
      months. The method had a sensitivity of 0.83, a specificity of 1.00 and a
      diagnostic accuracy of 0.90. CONCLUSION: An extended ELISA method for measuring
      anti-natalizumab antibody titres in multiple sclerosis patients on natalizumab
      therapy may be used for evaluation of antibody persistence. A test at three
      months may identify patients with high titres, who should discontinue natalizumab
      therapy, and patients with transient low-titre antibodies, who may continue
      natalizumab therapy despite development of antibodies.

PMID- 22454099
TI  - [Malignant lymphoma: therapy and assessment of the course].

PMID- 22454100
TI  - Thymic epithelial cells: antigen presenting cells that regulate T cell repertoire
      and tolerance development.
AB  - During thymocyte development bone marrow-derived precursors in the thymus undergo
      a series of differentiation steps to produce self-tolerant, mature T lymphocytes.
      The thymus contains two functionally distinct anatomical compartments, consisting
      of a centrally located medulla surrounded by the thymic cortex. These
      compartments in turn are comprised of two major cellular components: (1) the T
      lymphoid compartment of developing thymocytes and (2) the thymic stroma
      consisting mainly of thymic epithelial cells (TECs). These epithelial cells are
      further separated into cortical and medullary TECs (cTECs and mTECs) based on
      their localization within the thymic cortex or medulla respectively. Reciprocal
      interactions between thymocytes and epithelial cells are required for the
      development of both cellular components into a functional thymic organ.
      Thymocytes provide trophic factors for the development of a complex three
      dimensional epithelial cell network, while epithelial cells regulate T cell
      development through expression and presentation of self-antigens on major
      histocompatibility molecules. Our work focuses on how thymic epithelial cells
      regulate T cell development and function and on elucidating the mechanisms of
      thymic epithelial cell differentiation. Here we review current knowledge and
      provide our own insight into the development, differentiation and antigen
      presenting properties of TECs. We focus specifically on how mTECs regulate T cell
      repertoire selection and central tolerance.

PMID- 22454101
TI  - Diverse immune evasion strategies by human cytomegalovirus.
AB  - Members of the Herpesviridae family have the capacity to undergo both lytic and
      latent infection to establish a lifelong relationship with their host. Following
      primary infection, human cytomegalovirus (HCMV) can persist as a subclinical,
      recurrent infection for the lifetime of an individual. This quiescent portion of
      its life cycle is termed latency and is associated with periodic bouts of
      reactivation during times of immunosuppression, inflammation, or stress. In order
      to exist indefinitely and establish infection, HCMV encodes a multitude of immune
      modulatory mechanisms devoted to escaping the host antiviral response. HCMV has
      become a paradigm for studies of viral immune evasion of antigen presentation by
      both major histocompatibility complex (MHC) class I and II molecules. By
      restricting the presentation of viral antigens during both productive and latent
      infection, HCMV limits elimination by the human immune system. This review will
      focus on understanding how the virus manipulates the pathways of antigen
      presentation in order to modulate the host response to infection.

PMID- 22454102
TI  - Recognizing and reversing the immunosuppressive tumor microenvironment of head
      and neck cancer.
AB  - The estimated annual incidence of oral cavity and pharyngeal cancer is 39,000 in
      the United States and 260,000 cases worldwide. Despite significant advances in
      surgery, chemotherapy and radiotherapy, the 5-year survival rate for locally
      advanced head and neck tumors remains at 50 %. With further intensification of
      existing treatment limited by the already significant morbidity of multi-modality
      treatment, there is a clear need for novel therapeutic strategies [1].
      Accumulating evidence suggests that the tumor microenvironment of head and neck
      squamous cell carcinoma (HNSCC) is highly immunosuppressive, mediated by soluble
      and cell-associated inhibitory mediators and recruitment of host
      immunosuppressive cells. Thus, understanding and reversing the specific
      mechanisms underlying tumor-mediated immunosuppression in HNSCC is an important
      approach to generating an effective antitumor immune response, either as a
      component of immune-based therapy or as a complement to conventional treatment
      approaches. This article outlines significant immune-suppressive mechanisms in
      the HNSCC tumor microenvironment and potential approaches to enhancing the
      antitumor immune response.

PMID- 22454104
TI  - Efficient production of (R)-o-chloromandelic acid by deracemization of o
      chloromandelonitrile with a new nitrilase mined from Labrenzia aggregata.
AB  - (R)-o-Chloromandelic acid is the key precursor for the synthesis of
      Clopidogrel(r), a best-selling cardiovascular drug. Although nitrilases are often
      used as an efficient tool in the production of alpha-hydroxy acids, there is no
      practical nitrilase specifically developed for (R)-o-chloromandelic acid. In this
      work, a new nitrilase from Labrenzia aggregata (LaN) was discovered for the first
      time by genomic data mining, which hydrolyzed o-chloromandelonitrile with high
      enantioselectivity, yielding (R)-o-chloromandelic acid in 96.5% ee. The LaN was
      overexpressed in Escherichia coli BL21 (DE3), purified, and its catalytic
      properties were studied. When o-chloromandelonitrile was used as the substrate,
      the V(max) and K(m) of LaN were 2.53 MUmol min-1 mg-1 protein and 0.39 mM,
      respectively, indicating its high catalytic efficiency. In addition, a study of
      substrate spectrum showed that LaN prefers to hydrolyze arylacetonitriles. To
      relieve the substrate inhibition and to improve the productivity of LaN, a
      biphasic system of toluene-water (1:9, v/v) was adopted, in which o
      chloromandelonitrile of 300 mM (apparent concentration, based on total volume)
      could be transformed by LaN in 8 h, giving an isolated yield of 94.5%. The
      development of LaN makes it possible to produce (R)-o-chloromandelic acid by
      deracemizing o-chloromandelonitrile with good ee value and high substrate
      concentration.

PMID- 22454105
TI  - Microanatomical variation of the nasal capsular cartilage in newborn primates.
AB  - The breakdown of nasal capsule cartilage precedes secondary pneumatic expansion
      of the paranasal sinuses. Recent work indicates the nasal capsule of monkeys
      undergoes different ontogenetic transformations regionally (i.e., ossification,
      persistence as cartilage, or resorption). This study assesses nasal capsule
      morphology at the perinatal age in a taxonomically broad sample of non-human
      primates. Using traditional histochemical methods, osteopontin
      immunohistochemistry and tartrate-resistant acid phosphatase procedure, the
      cartilage of the lateral nasal wall (LNC) was studied. At birth, matrix
      properties differ between portions of the LNC that ultimately form elements of
      the ethmoid bone and regions of the LNC that have no postnatal (descendant)
      structure. The extent of cartilage that remains in the paranasal parts of the LNC
      varies among species. It is fragmented in species with the greatest extent of
      maxillary and/or frontal pneumatic expansion. Conversely, greater continuity of
      the LNC is noted in newborns of species that lack maxillary and/or frontal
      sinuses as adults. Chondroclasts occur adjacent to elements of the ethmoid bone,
      along the margin of the nasal tectum, and/or along islands of cartilage that bear
      no signs of ossification. Chondroclasts are prevalent along remnants of the
      paranasal LNC in tamarin species (Leontopithecus, Saguinus), which have extensive
      frontal and maxillary bone pneumatization. Taken together, the morphological
      observations indicate that the localized loss of cartilage might be considered a
      critical event at the onset of secondary pneumatization, facilitated by rapid
      recruitment of chondro-/osteoclasts, possibly occurring simultaneously in
      cartilage and bone.

PMID- 22454103
TI  - Effector functions of NLRs in the intestine: innate sensing, cell death, and
      disease.
AB  - Nucleotide-binding and oligomerization domain-like receptors (NLRs) are central
      regulators of pathogen recognition, the induction of innate immune effectors and
      inflammation with utmost importance in human diseases such as inflammatory bowel
      diseases. Most NLRs are key mediators of inflammasome complexes that activate
      caspase-1 and drive proteolytic processing of pro-inflammatory cytokines;
      however, a few tightly regulate inflammasome-independent activation of nuclear
      factor-kappaB and mitogen-activated protein kinase pathways. NLR signaling has
      evolved in intestinal epithelial cells to avoid overactive inflammatory responses
      toward the resident microbiota and to preserve epithelial barrier integrity and
      functions by maintaining homeostasis. In the present review, I examine new
      insights into the role of the NLRs in antimicrobial defenses. I pay particular
      attention to the emerging role of these receptors in engaging a complex cross
      talk between cell death and innate immunity pathways. Furthermore, I discuss the
      physiological functions of the NLRs in shaping the innate immune response within
      the intestine, maintaining homeostasis, inducing tissue repair following injury
      and promoting tumorigenesis.

PMID- 22454106
TI  - A nonelutable low-molecular weight heparin stent coating for improved
      thromboresistance.
AB  - Low-molecular weight heparin (LMWH) has been widely used as a systemic
      anticoagulant during percutaneous coronary intervention. In this study, LMWH was
      covalently immobilized to the surface of a cobalt chromium reservoir-based
      sirolimus-eluting stent to create a nonelutable nanoscale coating for enhanced
      thromboresistance. Toludine-blue stained stents revealed uniform heparin coverage
      on all surfaces of the stent. Scanning electron microscopy of stent strut cross
      sections showed identical coating thickness on all sides; while the thickness was
      determined to be 320 nm by a focus-ion beam system. Secondary ion mass
      spectrometry showed constant concentrations of O, N, and S atoms throughout the
      depth of the surface, confirming the uniformity of the heparin coating. The
      nonelutable nature of the coating was confirmed in a modified Factor Xa
      inhibition assay which showed the stent had an equivalent of 3-5 heparin
      units/cm(2), while no elutable heparin was detected in wash solutions. The
      antithrombin binding capacity of the immobilized heparin was determined to be 60
      80 pmol/cm(2) in an antithrombin uptake assay. The enhanced thromboresistance of
      the heparin coating was demonstrated in an in-vitro bovine blood flow loop which
      showed minimal visual thrombus accumulation and 95% reduction in platelet
      deposition compared to uncoated control stents. Drug-eluting stents with such
      nonelutable LMWH coating would represent a significant advance in the treatment
      of patients with complex lesions who are at increased risk of developing stent
      thrombosis.

PMID- 22454107
TI  - Holding back the microfilament--structural insights into actin and the actin
      monomer-binding proteins of apicomplexan parasites.
AB  - Parasites from the phylum Apicomplexa are responsible for several major diseases
      of man, including malaria and toxoplasmosis. These highly motile protozoa use a
      conserved actomyosin-based mode of movement to power tissue traversal and host
      cell invasion. The mode termed as 'gliding motility' relies on the dynamic
      turnover of actin, whose polymerisation state is controlled by a markedly limited
      number of identifiable regulators when compared with other eukaryotic cells.
      Recent studies of apicomplexan actin regulator structure-in particular those of
      the core triad of monomer-binding proteins, actin-depolymerising factor/cofilin,
      cyclase-associated protein/Srv2, and profilin-have provided new insights into
      possible mechanisms of actin regulation in parasite cells, highlighting divergent
      structural features and functions to regulators from other cellular systems.
      Furthermore, the unusual nature of apicomplexan actin itself is increasingly
      coming into the spotlight. Here, we review recent advances in understanding of
      the structure and function of actin and its regulators in apicomplexan parasites.
      In particular we explore the paradox between there being an abundance of
      unpolymerised actin, its having a seemingly increased potential to form filaments
      relative to vertebrate actin, and the apparent lack of visible, stable filaments
      in parasite cells.

PMID- 22454109
TI  - Optimising yeast as a host for recombinant protein production (review).
AB  - Having access to suitably stable, functional recombinant protein samples
      underpins diverse academic and industrial research efforts to understand the
      workings of the cell in health and disease. Synthesising a protein in recombinant
      host cells typically allows the isolation of the pure protein in quantities much
      higher than those found in the protein's native source. Yeast is a popular host
      as it is a eukaryote with similar synthetic machinery to the native human source
      cells of many proteins of interest, while also being quick, easy, and cheap to
      grow and process. Even in these cells the production of some proteins can be
      plagued by low functional yields. We have identified molecular mechanisms and
      culture parameters underpinning high yields and have consolidated our findings to
      engineer improved yeast cell factories. In this chapter, we provide an overview
      of the opportunities available to improve yeast as a host system for recombinant
      protein production.

PMID- 22454108
TI  - Reductive activation of the heme iron-nitrosyl intermediate in the reaction
      mechanism of cytochrome c nitrite reductase: a theoretical study.
AB  - Cytochrome c nitrite reductase catalyzes the six-electron, seven-proton reduction
      of nitrite to ammonia without release of any detectable reaction intermediate.
      This implies a unique flexibility of the active site combined with a finely tuned
      proton and electron delivery system. In the present work, we employed density
      functional theory to study the recharging of the active site with protons and
      electrons through the series of reaction intermediates based on nitrogen monoxide
      [Fe(II)-NO(+), Fe(II)-NO., Fe(II)-NO(-), and Fe(II)-HNO]. The activation barriers
      for the various proton and electron transfer steps were estimated in the
      framework of Marcus theory. Using the barriers obtained, we simulated the
      kinetics of the reduction process. We found that the complex recharging process
      can be accomplished in two possible ways: either through two consecutive proton
      coupled electron transfers (PCETs) or in the form of three consecutive elementary
      steps involving reduction, PCET, and protonation. Kinetic simulations revealed
      the recharging through two PCETs to be a means of overcoming the predicted deep
      energetic minimum that is calculated to occur at the stage of the Fe(II)-NO.
      intermediate. The radical transfer role for the active-site Tyr(218), as proposed
      in the literature, cannot be confirmed on the basis of our calculations. The role
      of the highly conserved calcium located in the direct proximity of the active
      site in proton delivery has also been studied. It was found to play an important
      role in the substrate conversion through the facilitation of the proton transfer
      steps.

PMID- 22454110
TI  - Which yeast species shall I choose? Saccharomyces cerevisiae versus Pichia
      pastoris (review).
AB  - Having decided on yeast as a production host, the choice of species is often the
      first question any researcher new to the field will ask. With over 500 known
      species of yeast to date, this could pose a significant challenge. However, in
      reality, only very few species of yeast have been employed as host organisms for
      the production of recombinant proteins. The two most widely used, Saccharomyces
      cerevisiae and Pichia pastoris, are compared and contrasted here.

PMID- 22454111
TI  - Preparation of Pichia pastoris expression plasmids.
AB  - When planning any heterologous expression experiment, the very first critical
      step is related to the design of the overall strategy, hence to the selection of
      the most adapted expression vector. The very flexible Pichia pastoris system
      offers a broad range of possibilities for the production of secreted, endogenous
      or membrane proteins thanks to a combination of various plasmid backbones,
      selection markers, promoters and fusion sequences introduced into dedicated host
      strains. The present chapter provides some guidelines on the choice of expression
      vectors and expression strategies. It also brings the reader a complete toolbox
      from which plasmids and fusion sequences can be picked and assembled to set up
      appropriate expression vectors. Finally, it provides standard starting protocols
      for the preparation of the selected plasmids and their use for host strain
      transformation.

PMID- 22454112
TI  - Preparation of Saccharomyces cerevisiae expression plasmids.
AB  - Expression plasmids for Saccharomyces cerevisiae offer a wide choice of vector
      copy number, promoters of varying strength and selection markers. These
      expression plasmids are usually shuttle vectors that can be propagated both in
      yeast and bacteria, making them useful in gene cloning. For heterologous
      production of membrane proteins, we used the green fluorescent protein (GFP)
      fusion technology which was previously developed in the Escherichia coli system.
      We designed an expression plasmid carrying an inducible GAL1 promoter, a gene
      encoding a membrane protein of interest and the GFP-octa-histidine sequence. Here
      we describe construction of multi-copy yeast expression plasmids by homologous
      recombination in S. cerevisiae.

PMID- 22454113
TI  - Codon optimisation for heterologous gene expression in yeast.
AB  - Heterologous protein production is used to amplify the yield of a desired protein
      target. To date, however, this is not a streamlined process: the factors defining
      an optimal protein production experiment are still poorly understood. This
      empirical exercise is particularly challenging for proteins of eukaryotic origin
      as well as those located in cellular membranes. The strong interest in structural
      and functional characterisation of eukaryotic membrane proteins-of which many are
      targets for different drugs-means that large amounts of pure protein, and hence
      high production levels in a suitable host, are required. On the genetic level,
      there are mainly two ways to positively influence the final yield of a desired
      protein target. First, the sequence surrounding the starting ATG can be altered
      and second the genetic code itself can be optimised to suit the selected host for
      production. The practical aspects of these two strategies will be discussed and
      exemplified in further detail in this chapter together with some hints and
      troubleshooting around different stages of the procedure.

PMID- 22454114
TI  - Yeast transformation to generate high-yielding clones.
AB  - There are several ways to introduce non-native DNA into yeast cells, including
      chemical transformation and electroporation. Methods for both of these procedures
      are outlined in this chapter. Both methods permit the uptake of DNA from the
      environment through yeast cell membranes and this DNA can be episomally
      maintained or integrated into the host genome. However, yeast cells must first be
      made competent to permit passive entry of the DNA and various methods are
      outlined in this chapter to facilitate this. All of the described methods can be
      applied in combination with antibiotic or auxotrophic selection pressure.

PMID- 22454115
TI  - Screening for high-yielding Pichia pastoris clones: the production of G protein
      coupled receptors as a case study.
AB  - Pichia pastoris is an established host for the production of a wide range of
      recombinant proteins including membrane proteins. The system has a particularly
      good track record for the production of G protein-coupled receptors (GPCRs).
      Generation and screening of expression clones with this system use standard
      molecular biology techniques. Multiple clones can be generated and screened in a
      matter of a few weeks making this similar to Escherichia coli in terms of speed.
      In addition, basic buffer components and the lack of expensive equipment make
      small-scale expression screening in P. pastoris very cost-effective. Here we
      describe the procedures used for small-scale GPCR production screening.

PMID- 22454116
TI  - Screening for high-yielding Saccharomyces cerevisiae clones: using a green
      fluorescent protein fusion strategy in the production of membrane proteins.
AB  - The overproduction of eukaryotic membrane proteins in milligram quantities is a
      major bottleneck for their further biochemical and structural investigation.
      Production trials exploring a range of input factors can be rationalized to
      improve the likelihood of success. Here we discuss some of these factors in
      combination with the use of a GFP-based Saccharomyces cerevisiae system that
      enables a quick turnaround time from clone construction to production trials.
      Since membrane-integrated levels do not necessarily correlate with the amount of
      functional recombinant protein, we also include the use of fluorescence-detection
      size exclusion chromatography (FSEC). Using FSEC, the quality of the recombinant
      material can also be rapidly evaluated as demonstrated for the functional
      production of the rat vesicular glutamate transporter (VGLUT2) and the human
      glucose transporter (GLUT1) (5).

PMID- 22454117
TI  - The effect of antifoam addition on protein production yields.
AB  - Pichia pastoris is a widely used host for recombinant protein production. The
      foaming associated with culturing it on a large scale is commonly prevented by
      the addition of chemical antifoaming agents or "antifoams." Unexpectedly, the
      addition of a range of antifoams to both shake flask and bioreactor cultures of
      P. pastoris has been shown to alter the total yield of the recombinant protein
      being produced. Possible explanations for this are that the presence of the
      antifoam increases the total amount of protein being produced and secreted per
      cell or that it increases the density of the culture. Antifoaming agents may
      therefore have specific effects on the growth and yield characteristics of
      recombinant cultures, in addition to their primary action as de-foamers.

PMID- 22454118
TI  - Setting up a bioreactor for recombinant protein production in yeast.
AB  - Scale-up from shake flasks to bioreactors allows for the more reproducible, high
      yielding production of recombinant proteins in yeast. The ability to control
      growth conditions through real-time monitoring facilitates further optimization
      of the process. The setup of a 3-L stirred-tank bioreactor for such an
      application is described.

PMID- 22454119
TI  - The implementation of a design of experiments strategy to increase recombinant
      protein yields in yeast (review).
AB  - Biological processes are subject to the influence of numerous factors and their
      interactions, which may be non-linear in nature. In a recombinant protein
      production experiment, understanding the relative importance of these factors,
      and their influence on the yield and quality of the recombinant protein being
      produced, is an essential part of its optimisation. In many cases, implementing a
      design of experiments (DoE) approach has delivered this understanding. This
      chapter aims to provide the reader with useful pointers in applying a DoE
      strategy to improve the yields of recombinant yeast cultures.

PMID- 22454120
TI  - Online analysis and process control in recombinant protein production (review).
AB  - Online analysis and control is essential for efficient and reproducible
      bioprocesses. A key factor in real-time control is the ability to measure
      critical variables rapidly. Online in situ measurements are the preferred option
      and minimize the potential loss of sterility. The challenge is to provide sensors
      with a good lifespan that withstand harsh bioprocess conditions, remain stable
      for the duration of a process without the need for recalibration, and offer a
      suitable working range. In recent decades, many new techniques that promise to
      extend the possibilities of analysis and control, not only by providing new
      parameters for analysis, but also through the improvement of accepted, well
      practiced, measurements have arisen.

PMID- 22454121
TI  - Monitoring the biomass accumulation of recombinant yeast cultures: offline
      estimations of dry cell mass and cell counts.
AB  - Biomass is one of the most important parameters for process optimization, scale
      up and control in recombinant protein production experiments. However, a standard
      unit of biomass remains elusive. Methods of biomass monitoring have increasingly
      been developed towards online, in situ techniques in order to advance process
      analysis and control. Offline, ex situ methods, such as dry cell mass
      determination and direct cell counts, remain the reference for determining cell
      mass and number, respectively, but this type of analysis is time consuming. In
      this chapter, protocols are presented for determining these offline measures of
      the biomass yield of recombinant yeast cultures.

PMID- 22454122
TI  - Online monitoring of biomass accumulation in recombinant yeast cultures.
AB  - Methods of biomass monitoring have increasingly been developed towards online, in
      situ techniques in order to advance process analysis and control. Off-line, ex
      situ methods, such as dry cell mass determination and direct cell counts, remain
      the reference for determining cell mass and number, respectively, but this type
      of analysis is time consuming. Absorbance measurement, which is used extensively
      as an off-line, ex situ, or online, in situ technique, is fast and
      straightforward, as the absorbance can be correlated to cell mass and number by a
      simple calibration. The downside is that absorbance measurements provide no
      estimation of viability and in situ applications can suffer from interference,
      such as aeration. Impedance spectroscopy is widely available and provides a quick
      measure of viable cell concentration, but does not give an estimation of total
      cell concentration and, hence, potential product. Sensitivity of impedance
      spectroscopy remains an issue at low cell concentration, and interference during
      in situ measurements is also a significant factor. In this chapter, a range of
      protocols is presented for online determination of biomass yields of recombinant
      yeast cultures.

PMID- 22454123
TI  - Optimising Pichia pastoris induction.
AB  - A common method for inducing the production of recombinant proteins in Pichia
      pastoris is through the use of methanol. However, the by-products of methanol
      metabolism are toxic to yeast cells and therefore its addition to recombinant
      cultures must be controlled and monitored throughout the process in order to
      maximise recombinant protein yields. Described here are online and off-line
      methods to monitor and control methanol addition to bench-top-scale bioreactors.

PMID- 22454124
TI  - Optimizing Saccharomyces cerevisiae induction regimes.
AB  - Recombinant membrane protein yields can be optimized in Saccharomyces cerevisiae
      by adjusting the induction time and temperature and/or by the addition of
      chemical chaperones. Here we describe a protocol for assessing the importance of
      these parameters.

PMID- 22454125
TI  - Large-scale production of membrane proteins in Pichia pastoris: the production of
      G protein-coupled receptors as a case study.
AB  - One of the major advantages of using Pichia pastoris is that it is readily
      adapted to large-scale culture in bioreactors. Bioreactors allow precise
      regulation of cell growth parameters increasing both yields and reproducibility
      of the culture. P. pastoris cultures grow to very high cell densities which helps
      minimise culture volume and facilitates downstream processing of the sample.
      Here, we provide protocols for the large-scale production of the human adenosine
      A(2A) receptor (A(2A)R) and provide some details of how bioreactor cultures can
      be used for optimisation of expression of the human dopamine D2 receptor (D2DR).

PMID- 22454126
TI  - Large-scale production of membrane proteins in Saccharomyces cerevisiae: using a
      green fluorescent protein fusion strategy in the production of membrane proteins.
AB  - The production of membrane proteins in the large quantities necessary for
      structural analysis requires many optimization steps. The GFP-fusion-based scheme
      described in earlier chapters ( Chapters 4 , 8 , and 16 ) facilitates these steps
      by allowing the selection of high yielding clones that produce detergent-stable
      membrane proteins. Here, we describe the experimental steps required to establish
      the reproducible, large-scale production and purification of membrane protein-GFP
      fusions using S. cerevisiae.

PMID- 22454127
TI  - Large-scale production of secreted proteins in Pichia pastoris.
AB  - The production of recombinant therapeutic proteins is an active area of research
      in drug development. These bio-therapeutic drugs target nearly 150 disease states
      and promise to bring better treatments to patients. However, if new bio
      therapeutics are to be made more accessible and affordable, improvements in
      production performance and optimization of processes are necessary. A major
      challenge lies in controlling the effect of process conditions on production of
      intact functional proteins. To achieve this, improved tools are needed for bio
      processing. For example, implementation of process modeling and high-throughput
      technologies can be used to achieve quality by design, leading to improvements in
      productivity. Commercially, the most sought after targets are secreted proteins
      due to the ease of handling in downstream procedures. This chapter outlines
      different approaches for production and optimization of secreted proteins in the
      host Pichia pastoris.

PMID- 22454128
TI  - Disruption of yeast cells to isolate recombinant proteins.
AB  - Yeast is a proven host for the production of recombinant proteins, which may be
      incorporated in cellular membranes or localized in subcellular compartments. In
      order to gain access to these proteins, cellular disruption is required to permit
      extraction, purification, and downstream analysis. Disruption can significantly
      impact the yield and quality of the biomaterial. We highlight several disruption
      techniques that are applicable to yeast cells ranging from mechanical to
      nonmechanical approaches. In all cases fast, efficient cellular disruption is
      desirable, that does not alter the protein chemically or physically and that
      generates material for downstream purification and analysis.

PMID- 22454129
TI  - Topical photodynamic treatment with poly-L-lysine-chlorin p6 conjugate improves
      wound healing by reducing hyperinflammatory response in Pseudomonas aeruginosa
      infected wounds of mice.
AB  - We report the results of our investigations on the effect of antimicrobial
      photodynamic treatment (APDT) with poly-lysine-conjugated chlorin p6 (pl-cp6) on
      proinflammatory cytokine expression and wound healing in a murine excisional
      wound model infected with Pseudomonas aeruginosa. Treatment of infected wounds
      with pl-cp6 and light doses of 60 and 120 J/cm(2) reduced the bacterial load by
      ~1.5 and 2.0 log, respectively, after 24 h. The treated wounds healed ~5 days
      earlier as compared to untreated control and wound closure was not dependent on
      light dose. Interestingly, at 96 h post-treatment, drug-treated wounds irradiated
      at 60 J/cm(2) showed considerable reduction of proinflammatory cytokines IL-6
      (approximately five times) and TNF-alpha (approximately four times) compared to
      untreated control. Further, exposure of culture supernatants to similar light
      dose and pl-cp6 concentration under in vitro conditions reduced the protease
      activity by ~50 % as compared to the untreated control, suggesting inactivation
      of extracellular virulent factors. Additionally, histological analysis of treated
      infected wounds showed complete reepithelialization, ordered collagen fibers, and
      considerable decrease in inflammatory cell infiltration compared to untreated
      wounds. These results imply that pl-cp6-mediated PDT reduces hyperinflammatory
      response of infected wounds, leading to acceleration of wound healing.

PMID- 22454130
TI  - Transcription factors are targeted by differentially expressed miRNAs in
      primates.
AB  - MicroRNAs (miRNAs) are small RNA molecules involved in the regulation of
      mammalian gene expression. Together with other transcription regulators, miRNAs
      modulate the expression of genes and thereby potentially contribute to tissue and
      species diversity. To identify miRNAs that are differentially expressed between
      tissues and/or species, and the genes regulated by these, we have quantified
      expression of miRNAs and messenger RNAs in five tissues from multiple human,
      chimpanzee, and rhesus macaque individuals using high-throughput sequencing. The
      breadth of this tissue and species data allows us to show that downregulation of
      target genes by miRNAs is more pronounced between tissues than between species
      and that downregulation is more pronounced for genes with fewer binding sites for
      expressed miRNAs. Intriguingly, we find that tissue- and species-specific miRNAs
      target transcription factor genes (TFs) significantly more often than expected.
      Through their regulatory effect on transcription factors, miRNAs may therefore
      exert an indirect influence on a larger proportion of genes than previously
      thought.

PMID- 22454132
TI  - Social support and subsequent disability: it is not the size of your network that
      counts.
AB  - BACKGROUND: high levels of social support and engagement may help sustain good
      health and functional ability. However, the definition of social support in
      previous research has been inconsistent and findings are mixed. The aim of this
      analysis was to explore the effect of two aspects of social support on subsequent
      disability in a group of community dwelling older women and men. METHODS: data
      were drawn from two concurrent prospective observational cohort studies of
      community-based older Australian women (N = 2,013) and men (N = 680). Baseline
      and follow-up data were drawn from the second (1999) and fifth (2008) surveys of
      the women and the second (2001) and third (2008) surveys of the men. At baseline,
      social support was measured by the two subscales (social network and subjective
      support) of the Duke Social Support Index (DSSI). The outcome measure was
      Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living
      (IADLs). RESULTS: overall, social network size was not associated with subsequent
      disability in either women or men. After adjusting for health status at baseline,
      lack of satisfaction with social support was associated with greater difficulties
      in ADLs and IADLs for both women and men. CONCLUSIONS: our results suggest that
      the provision of social support is insufficient to limit subsequent disability:
      support provided must be subjectively perceived to be relevant and adequate.

PMID- 22454131
TI  - Revealing mammalian evolutionary relationships by comparative analysis of gene
      clusters.
AB  - Many software tools for comparative analysis of genomic sequence data have been
      released in recent decades. Despite this, it remains challenging to determine
      evolutionary relationships in gene clusters due to their complex histories
      involving duplications, deletions, inversions, and conversions. One concept
      describing these relationships is orthology. Orthologs derive from a common
      ancestor by speciation, in contrast to paralogs, which derive from duplication.
      Discriminating orthologs from paralogs is a necessary step in most multispecies
      sequence analyses, but doing so accurately is impeded by the occurrence of gene
      conversion events. We propose a refined method of orthology assignment based on
      two paradigms for interpreting its definition: by genomic context or by sequence
      content. X-orthology (based on context) traces orthology resulting from
      speciation and duplication only, while N-orthology (based on content) includes
      the influence of conversion events. We developed a computational method for
      automatically mapping both types of orthology on a per-nucleotide basis in gene
      cluster regions studied by comparative sequencing, and we make this mapping
      accessible by visualizing the output. All of these steps are incorporated into
      our newly extended CHAP 2 package. We evaluate our method using both simulated
      data and real gene clusters (including the well-characterized alpha-globin and
      beta-globin clusters). We also illustrate use of CHAP 2 by analyzing four more
      loci: CCL (chemokine ligand), IFN (interferon), CYP2abf (part of cytochrome P450
      family 2), and KIR (killer cell immunoglobulin-like receptors). These new methods
      facilitate and extend our understanding of evolution at these and other loci by
      adding automated accurate evolutionary inference to the biologist's toolkit. The
      CHAP 2 package is freely available from http://www.bx.psu.edu/miller_lab.

PMID- 22454133
TI  - Managing patients with COPD exacerbation: does age matter?
AB  - INTRODUCTION: there is little information about the relationship between age and
      management of COPD exacerbation (AECOPD), although older persons are known to be
      at a greater risk of hospital admission. METHODS: we have investigated responses
      from the clinical and patient questionnaire elements of the 2008 UK COPD audit,
      splitting the data into age decile. RESULTS: age ranged from 27 to 102. Patient
      reported data suggested older patients had inferior knowledge of COPD, undertook
      less self-care and were less likely to recognise symptoms of exacerbation prior
      to hospitalisation. Clinician-reported data showed that although older patients
      had severe disease and symptoms, greater co-morbidity at presentation and higher
      mortality, fewer were seen in hospital or followed up subsequently by respiratory
      specialists. Older patients were more likely to have a DNR order signed within 24
      h of admission, irrespective of co-morbidities or performance status. The
      observations were particularly applicable to those aged 80 or above. CONCLUSIONS:
      clinicians should consider increasing age as a specific risk factor in the
      management of COPD. Acute units and community teams should review carefully their
      protocols and pathways for how they assess, manage, discharge and follow-up older
      patients with COPD exacerbation.

PMID- 22454134
TI  - Prevalence of frailty phenotypes and risk of mortality in a community-dwelling
      elderly cohort.
AB  - OBJECTIVES: to determine the prevalence of three independent, disability-free and
      operationally defined frailty phenotypes and the associated risk of mortality in
      a community-dwelling older people cohort over 74 years of age. METHODS:
      observational, prospective and population-based design. Bio-psycho-social
      variables were assessed using a range of standardised instruments. The physical
      frailty phenotype (PFP), mental frailty phenotype (MFP) and social frailty
      phenotype (SFP) were operationally defined using a deficit accumulation model
      that excluded disability. Logistic regression analyses explored associations of
      the frailty phenotypes with sex, age and marital status, and a Cox proportional
      hazard regression analysis was performed to evaluate the association between
      frailty phenotypes and mortality. RESULTS: of the eligible individuals, 82% (n =
      875) participated. The prevalence of any frailty phenotype in an individual was
      38.8%; 17.3% exhibited the PFP, 20.2% exhibited the MFP, and 8.9% exhibited the
      SPF. Older and female were more likely to exhibit the PFP, and widowhood was
      associated with the SFP. The hazard ratios of mortality were 3.09 (95% CI = 1.54
      6.17) for the PFP and 2.69 (95% CI = 1.01-7.25) for the SFP. CONCLUSION: three
      different disability-free frailty phenotypes were differentially related to the
      socio-demographical characteristics of sex, age and marital status and
      independently predicted risk of mortality.

PMID- 22454135
TI  - Dementia in acute hospital inpatients: the role of the geriatrician.

PMID- 22454136
TI  - Design and evaluation of a novel evodiamine-phospholipid complex for improved
      oral bioavailability.
AB  - A novel evodiamine (EVO)-phospholipid complex (EPLC) was designed to improve the
      bioavailability of EVO. A central composite design approach was employed for
      process optimization. EPLC were characterized by differential scanning
      calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy,
      (1)H-NMR spectroscopy, matrix-assisted laser desorption/ionization time-of-flight
      spectroscopy, apparent solubility, and dissolution rate. After oral
      administration of EPLC, the concentrations of EVO at different time points were
      determined by high-performance liquid chromatography. The optimal formulation for
      EPLC was obtained where the values of X (1), X (2), and X (3) were 2, 0.5, and
      2.5 mg/mL, respectively. The average particle size and zeta potential of EPLC
      with the optimized formulation were 246.1 nm and -26.94 mV, respectively. The EVO
      and phospholipids in the EPLC were associated with non-covalent interactions. The
      solubility of EPLC in water and the dissolution rate of EPLC in phosphate
      buffered solution (pH 6.8) were substantially enhanced. The plasma EVO
      concentration-time curves of EPLC and free EVO were both in accordance with the
      two-compartment model. The peak concentration and AUC(0-infinity) of EPLC were
      increased, and the relative bioavailability was significantly increased to 218.82
      % compared with that of EVO.

PMID- 22454137
TI  - Interventional closure of atrial septal defects without fluoroscopy in adult and
      pediatric patients.
AB  - BACKGROUND: Interventional closure of atrial septal defects (ASDs) with a
      transcatheter device is the preferred strategy in children and adults. This
      procedure has been proven in numerous studies, but X-ray and contrast agent
      exposure is still a major side effect. The aim of this study was to clarify
      whether the interventional closure of ASDs is possible and safe if it is guided
      by transesophageal echocardiography (TEE) alone. METHODS AND RESULTS: We
      retrospectively selected and studied pediatric and adult patients with
      interventional closure of ASDs at the Deutsches Herzzentrum Berlin (DHZB) without
      fluoroscopy between 1999 and 2010. We included 330 out of 1,605 patients; 254 had
      an ASD II, 30 a PFO and 46 multiperforated atrial septum. Median age was 8.92
      (0.96-76.3) years and median body weight 32.6 (8.3-156) kg. Median stretched
      defect size was 13 (5-29) mm. Median procedure time was 50 (20-170) min. Closure
      was performed in the majority of patients with the Amplatzer((r)) septal occluder
      or Amplatzer((r)) PFO occluder. The procedure succeeded in 98.2 % of cases and
      closure rate was 94.9 % after 48 h. Complication rate was low and procedure time
      was similar to that necessary with studies using fluoroscopy. CONCLUSION:
      Interventional closure of ASDs is safe and effective if guided with TEE alone.
      The results can compete with those with the use of fluoroscopy. TEE-guided
      closure of ASD should be considered in more catheter laboratories to avoid
      unnecessary radiation exposure for the patient and the examiner.

PMID- 22454138
TI  - Prognostic relevance of heart rate at rest for survival and the quality of life
      in patients with dilated cardiomyopathy.
AB  - OBJECTIVES: Reduction of resting heart rate (HR) has been suggested as a novel
      therapeutic approach in patients with chronic heart failure because it has been
      shown to prolong survival and also to improve health-related quality of life (Hr
      QoL). The purpose of this analysis was to assess the prognostic impact of resting
      HR in patients with dilated cardiomyopathy (DCM). METHODS: 217 patients with DCM
      confirmed by endomyocardial biopsy were investigated (age 49 +/- 11 years, 20.7 %
      were female). The study population was divided into two groups according to the
      median of the resting HR. After a median follow-up time of 7.4 years overall
      survival and health-related quality of life (Hr-QoL) were compared in both
      groups. Survival was compared using Kaplan-Meier method and Hr-QoL was assessed
      using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS:
      Elevated resting HR was associated with poor 1-year survival (p = 0.03). In
      contrast, long-term survival was not affected by HR (p = 0.20). Patients with
      lower HR at rest scored significantly lower on the MLHFQ (20 vs. 36, p = 0.03),
      indicating that higher resting HR is associated with an impairment of Hr-QoL.
      CONCLUSIONS: Increased HR might be used as a diagnostic tool to identify patients
      at risk. Reduction of resting HR in patients with DCM might be a therapeutic
      option to improve Hr-QoL and therefore merits further investigation in future
      studies.

PMID- 22454139
TI  - Biotribological study of large diameter ceramic-on-CFR-PEEK hip joint including
      fluid uptake, wear and frictional heating.
AB  - A novel material combination of a large diameter Biolox((r)) Delta zirconia
      toughened-alumina (ZTA) head and a pitch-based carbon fibre reinforced poly ether
      ether-ketone (CFR-PEEK) MOTIS((r)) cup has been studied. The acetabular cups were
      inclined at three angles and tested using Durham Hip Simulators. The different
      inclination angles used did not have a significant effect on the wear rates
      (ANOVA, p = 0.646). Averaged over all cups, the wear rates were calculated to be
      0.551 +/- 0.115 mm(3)/10(6) cycles and 0.493 +/- 0.107 mm(3)/10(6) cycles taking
      into account two types of soak controls; loaded at room temperature and unloaded
      at 37  degrees C respectively. Averaged across all femoral heads, the wear rate
      was 0.243 +/- 0.031 mm(3)/10(6) cycles. The temperature change of the lubricant
      caused by the frictional heat was measured in situ. Friction factors measured
      using the Durham Friction Simulator were lower for the worn CFR-PEEK cups
      compared with unworn. This correlated with the decreased surface roughness. Even
      though relatively high friction was observed in these hemispherical hard-on-soft
      bearings, the wear rate is encouragingly low.

PMID- 22454140
TI  - Biomechanical and structural changes following the decellularization of bovine
      pericardial tissues for use as a tissue engineering scaffold.
AB  - To achieve natural scaffolds for tissue engineering applications we
      decellularized bovine pericardial (BP) tissues according to two different
      protocols: a novel treatment based on Triton((r)) X-100 (12 h, 4  degrees C)
      (BP1) and a trypsin/EDTA treatment (37  degrees C, 48 h) (BP2). Results were
      compared with commercially available acellular xenogeneic biomaterials,
      Veritas((r)) and Collamed((r)). Biomechanical characteristics, high (E(h)) and
      low (E(l)) modulus of elasticity, of the fresh untreated tissue varied with the
      anatomical direction (apex to base (T) to transverse (L)) (mean +/- SDEV): (41.63
      +/- 14.65-48.12 +/- 10.19 MPa and 0.27 +/- 0.05-0.30 +/- 0.12 MPa respectively).
      BP1 had no mechanical effect (44.65 +/- 19.73-52.67 +/- 7.59 MPa and 0.37 +/-
      0.14-0.37 +/- 0.11 MPa, respectively) but BP2 resulted in significant decrease in
      E(h) and E(l) (20.96 +/- 8.17-36.82 +/- 3.23 MPa and 0.20 +/- 0.06-0.23 +/- 0.06
      MPa). Hysteresis ratio (h) varied (19-26 % of the loading energy) independently
      of anatomical direction. Glycosaminoglycans content was unaffected by BP1, while
      22 % of chondroitin/dermatan sulphate and 60 % of hyaluronan were removed after
      BP2 treatment. Endothelial cell adhesion was achieved after 24 h and 3 days cell
      culture.

PMID- 22454141
TI  - Pilot fMRI investigation of representational plasticity associated with motor
      skill learning and its functional consequences.
AB  - Complex skill learning at a joint initiates competition between its
      representation in the primary motor cortex (M1) and that of the neighboring
      untrained joint. This process of representational plasticity has been mapped by
      cortically-evoking simple movements. We investigated, following skill learning at
      a joint, 1) whether comparable processes of representational plasticity are
      observed when mapping is based on volitionally produced complex movements and 2)
      the consequence on the skill of the adjacent untrained joint. Twenty-four healthy
      subjects were assigned to either finger- or elbow-skill training or no-training
      control group. At pretest and posttest, subjects performed complex skill
      movements at finger, elbow and ankle concurrent with functional magnetic
      resonance imaging (fMRI) to define learning and allow mapping of corresponding
      activation-based representations in M1. Skill following both finger- and elbow-
      training transferred to the ankle (remote joint) (p = 0.05 and 0.05); however,
      finger training did not transfer to the elbow and elbow training did not transfer
      to the finger. Following finger training, location of the trained finger
      representation showed a trend (p = 0.08) for medial shift towards the
      representation of adjacent untrained elbow joint; the change in intensity of the
      latter representation was associated with elbow skill (Spearman's rho = -0.71, p
      = 0.07). Following elbow training, the trained elbow representation and the
      adjacent untrained finger representation increased their overlap (p = 0.02),
      which was associated with finger skill (Spearman's rho = -0.83, p = 0.04). Thus,
      our pilot study reveals comparable processes of representational plasticity with
      fMRI mapping of complex skill movements as have been demonstrated with cortically
      evoked methods. Importantly, these processes may limit the degree of transfer of
      skill between trained and adjacent untrained joints. These pilot findings that
      await confirmation in large-scale studies have significant implications for neuro
      rehabilitation. For instance, techniques, such as motor cortical stimulation,
      that can potentially modulate processes of representational plasticity between
      trained and adjacent untrained representations, may optimize transfer of skill.

PMID- 22454142
TI  - Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant
      peripheral nerve sheath tumor (MPNST) cells.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas able to grow under
      conditions of metabolic stress caused by insufficient nutrients or oxygen. Both
      pituitary adenylate cyclase-activating polypeptide (PACAP) and activity-dependent
      neuroprotective protein (ADNP) have glioprotective potential. However, whether
      PACAP/ADNP signaling is involved in the resistance to cell death in MPNST cells
      remains to be clarified. Here, we investigated the involvement of this signaling
      system in the survival response of MPNST cells against hydrogen peroxide
      (H(2)O(2))-evoked death both in the presence of normal serum (NS) and in serum
      starved (SS) cells. Results showed that ADNP levels increased time-dependently (6
      48 h) in SS cells. Treatment with PACAP38 (10(-9) to 10(-5) M) dose-dependently
      increased ADNP levels in NS but not in SS cells. PAC(1)/VPAC receptor antagonists
      completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP
      expression in SS cells. NS-cultured cells exposed to H(2)O(2) showed
      significantly reduced cell viability (~50 %), increased p53 and caspase-3, and
      DNA fragmentation, without affecting ADNP expression. Serum starvation
      significantly reduced H(2)O(2)-induced detrimental effects in MPNST cells, which
      were not further ameliorated by PACAP38. Altogether, these finding provide
      evidence for the involvement of an endogenous PACAP-mediated ADNP signaling
      system that increases MPNST cell resistance to H(2)O(2)-induced death upon serum
      starvation.

PMID- 22454143
TI  - Neurotrophin expression is not affected in uteri of women with adenomyosis.
AB  - To investigate the involvement of neurotrophins and nerve fibres in the
      pathogenesis of adenomyosis, we performed a retrospective, clinical study.
      Hysterectomy specimens from 40 patients with histologically proven adenomyosis
      and from 20 patients without adenomyosis or endometriosis were used for
      immunohistochemical analysis. In order to investigate neurotrophic properties in
      adenomyosis, the antibodies against nerve growth factor (NGF), neurotrophin 3 (NT
      3), the high-affinity NGF receptor (TrkA), the low-affinity neurotrophin receptor
      (p75(NTR)), the neuronal marker S100 (for myelinated nerve fibres) and protein
      gene product 9.5 (PGP9.5; for intact nerve fibres) were used. There was no
      significant difference in the NGF, NT-3 and p75(NTR) expression in the myometrium
      or endometrium between the adenomyosis and the control group. The nerve fibre
      density (S100, PGP9.5 and p75(NTR)) did not significantly differ between the
      adenomyosis and control group, the nerve fibre density of the adenomyosis group
      was tendentially decreased when compared with the nonporous control group. The
      present study suggests that endometrial and uterine neurotrophin expression and
      endometrial innervation are not altered in adenomyosis; however, women with
      adenomyosis or with adenomyosis/endometriosis tendentially had less myometrial
      nerve fibres than the control group.

PMID- 22454144
TI  - Molecular mapping of qualitative and quantitative loci for resistance to
      Leptosphaeria maculans causing blackleg disease in canola (Brassica napus L.).
AB  - Blackleg, caused by Leptosphaeria maculans, is one of the most important diseases
      of oilseed and vegetable crucifiers worldwide. The present study describes (1)
      the construction of a genetic linkage map, comprising 255 markers, based upon
      simple sequence repeats (SSR), sequence-related amplified polymorphism, sequence
      tagged sites, and EST-SSRs and (2) the localization of qualitative (race
      specific) and quantitative (race non-specific) trait loci controlling blackleg
      resistance in a doubled-haploid population derived from the Australian canola
      (Brassica napus L.) cultivars Skipton and Ag-Spectrum using the whole-genome
      average interval mapping approach. Marker regression analyses revealed that at
      least 14 genomic regions with LOD >= 2.0 were associated with qualitative and
      quantitative blackleg resistance, explaining 4.6-88.9 % of genotypic variation. A
      major qualitative locus, designated RlmSkipton (Rlm4), was mapped on chromosome
      A7, within 0.8 cM of the SSR marker Xbrms075. Alignment of the molecular markers
      underlying this QTL region with the genome sequence data of B. rapa L. suggests
      that RlmSkipton is located approximately 80 kb from the Xbrms075 locus. Molecular
      marker-RlmSkipton linkage was further validated in an F(2) population from
      Skipton/Ag-Spectrum. Our results show that SSR markers linked to consistent
      genomic regions are suitable for enrichment of favourable alleles for blackleg
      resistance in canola breeding programs.

PMID- 22454145
TI  - Quantitative trait loci responsible for Fusarium head blight resistance in
      Chinese landrace Baishanyuehuang.
AB  - Fusarium head blight (FHB), mainly caused by Fusarium graminearum, is a
      destructive disease that can significantly reduce grain yield and quality.
      Deployment of quantitative trait loci (QTLs) for FHB resistance in commercial
      cultivars has been the most effective approach for minimizing the disease losses.
      'Baishanyuehuang' is a highly FHB-resistant landrace from China. Recombinant
      inbred lines (RILs) developed from a cross of 'Baishanyuehuang' and 'Jagger' were
      evaluated for FHB resistance in three greenhouse experiments in 2010 and 2011 by
      single-floret inoculation. Percentage of symptomatic spikelets in an inoculated
      spike was recorded 18 days post-inoculation. The RIL population was screened with
      251 polymorphic simple sequence repeats. Four QTLs were associated with FHB
      resistance and mapped on three chromosomes. Two QTLs were located on the short
      arm of chromosome 3B (3BS) with one in distal of 3BS and another near centromere
      (3BSc), designated as Qfhb.hwwg-3BSc. The QTL in the distal of 3BS is flanked by
      Xgwm533 and Xgwm493, thus corresponds to Fhb1. This QTL explained up to 15.7 % of
      phenotypic variation. Qfhb.hwwg-3BSc flanked by Xwmc307 and Xgwwm566 showed a
      smaller effect than Fhb1 and explained up to 8.5 % of phenotypic variation. The
      other two QTLs were located on 3A, designated as Qfhb.hwwg-3A, and 5A, designated
      as Qfhb.hwwg-5A. Qfhb.hwwg-3A was flanked by Xwmc651 and Xbarc356 and explained
      4.8-7.5 % phenotypic variation, and Qfhb.hwwg-5A was flanked by markers Xgwm186
      and Xbarc141, detected in only one experiment, and explained 4.5 % phenotypic
      variation for FHB resistance. 'Baishanyuehuang' carried all resistance alleles of
      the four QTL. Qfhb.hwwg-3BSc and Qfhb.hwwg-3A were new QTLs in 'Baishanyuehuang'.
      'Baishanyuehuang' carries a combination of QTLs from different sources and can be
      a new source of parent to pyramid FHB-resistant QTLs for improving FHB resistance
      in wheat.

PMID- 22454146
TI  - Population structure and linkage disequilibrium in Lupinus albus L. germplasm and
      its implication for association mapping.
AB  - White lupin (Lupinus albus L.) has been around since 300 B.C. and is recognized
      for its ability to grow on poor soils and application as green manure in addition
      to seed harvest. The seed has very high levels of protein (33-47 %) and oil (6-13
      %). It also has many secondary metabolites that are potentially of nutraceutical
      value to animals and humans. Despite such a great potential, lupins role in
      modern agriculture began only in the twentieth century. Although a large
      collection of Lupinus germplasm accessions is available worldwide, rarely have
      they been genetically characterized. Additionally, scarce genomic resources in
      terms of recombinant populations and genome information have been generated for
      L. albus. With the advancement in association mapping methods, the natural
      populations have the potential to replace the recombinant populations in gene
      mapping and marker-trait associations. Therefore, we studied the genetic
      similarity, population structure and marker-trait association in a USDA germplasm
      collection for their current and future application in this crop improvement. A
      total of 122 PI (Plant Inventory) lines were screened with 18 AFLP primer pairs
      that generated 2,277 fragments. A subset of 892 polymorphic markers with MAF
      >0.05 (minor allele frequency) were used for association mapping. The cluster
      analysis failed to group accessions on the basis of their passport information,
      and a weak structure and low linkage disequilibrium (LD) were observed indicating
      the usefulness of the collection for association mapping. Moreover, we were also
      able to identify two markers (a p value of 1.53 * 10(-4) and 2.3 * 10(-4)) that
      explained 22.69 and 20.5 % of seed weight variation determined using R (LR) (2) .
      The implications of lack of geographic clustering, population structure, low LD
      and the ability of AFLP to map seed weight trait using association mapping and
      the usefulness of the PI collections in breeding programs are discussed.

PMID- 22454147
TI  - AMPK activation by dihydrotestosterone reduces FSH-stimulated cell proliferation
      in rat granulosa cells by inhibiting ERK signaling pathway.
AB  - We have previously reported that 5alpha-dihydrotestosterone (DHT) inhibits FSH
      mediated granulosa cell proliferation by reducing cyclin D2 mRNA expression and
      blocking cell cycle progression at G1/S phase. The present study investigated the
      role of AMP activated protein kinase (AMPK) in DHT-mediated inhibition of
      granulosa cell proliferation. Granulosa cells harvested from 3-d estradiol primed
      immature rats were exposed to different concentrations of DHT (0, 45, and 90
      ng/ml) for 24 h. Western blot analysis of immunoprecipitated AMPK showed a dose
      dependent activation (P < 0.05) as evidenced by the increased phosphorylation at
      thr 172. In addition, time-courses studies (0, 6, 12, and 24 h) using DHT (90
      ng/ml) showed a time-dependent increase in AMPK activation with maximum effect at
      24 h. FSH inhibited AMPK phosphorylation and promoted granulosa cell
      proliferation, but pretreatment with DHT (90 ng/ml) for 24 h prior to FSH
      treatment reduced this effect. Pharmacological activation of AMPK with 5
      aminoimidazole-4-carboxamide-1-beta4-ribofuranoside abolished FSH-mediated ERK
      phosphorylation, indicating that AMPK is a negative upstream regulator of ERK.
      Furthermore, inhibition of AMPK activation by compound C reversed the DHT
      mediated reduction in positive cell cycle regulator, cyclin D2, and 5-bromo-2'
      deoxyuridine incorporation. These results suggest that elevated levels of DHT
      activate AMPK, which in turn inhibits ERK phosphorylation. Thus, inhibition of
      ERK phosphorylation by activated AMPK in response to DHT might contribute to
      decreased granulosa cell mitogenesis and ovulatory dysfunction seen in
      hyperandrogenic states.

PMID- 22454148
TI  - The dorsomedial suprachiasmatic nucleus times circadian expression of Kiss1 and
      the luteinizing hormone surge.
AB  - Ovulation in mammals is gated by a master circadian clock in the suprachiasmatic
      nucleus (SCN). GnRH neurons represent the converging pathway through which the
      brain triggers ovulation, but precisely how the SCN times GnRH neurons is
      unknown. We tested the hypothesis that neurons expressing kisspeptin, a
      neuropeptide coded by the Kiss1 gene and necessary for the activation of GnRH
      cells during ovulation, represent a relay station for circadian information that
      times ovulation. We first show that the circadian increase of Kiss1 expression,
      as well as the activation of GnRH cells, relies on intact ipsilateral neural
      input from the SCN. Second, by desynchronizing the dorsomedial (dm) and
      ventrolateral (vl) subregions of the SCN, we show that a clock residing in the
      dmSCN acts independently of the light-dark cycle, and the vlSCN, to time Kiss1
      expression in the anteroventral periventricular nucleus of the hypothalamus and
      that this rhythm is always in phase with the LH surge. In addition, we show that
      although the timing of the LH surge is governed by the dmSCN, its amplitude
      likely depends on the phase coherence between the vlSCN and dmSCN. Our results
      suggest that whereas dmSCN neuronal oscillators are sufficient to time the LH
      surge through input to kisspeptin cells in the anteroventral periventricular
      nucleus of the hypothalamus, the phase coherence among dmSCN, vlSCN, and extra
      SCN oscillators is critical for shaping it. They also suggest that female
      reproductive disorders associated with nocturnal shift work could emerge from the
      desynchronization between subregional oscillators within the master circadian
      clock.

PMID- 22454150
TI  - Evolutionary origin of the structure and function of gonadotropin-inhibitory
      hormone: insights from lampreys.
AB  - Gonadotropin (GTH)-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide
      that inhibits GTH secretion in mammals and birds by acting on gonadotropes and
      GnRH neurons within the hypothalamic-pituitary-gonadal axis. GnIH and its
      orthologs that have an LPXRFamide (X = L or Q) motif at the C terminus
      (LPXRFamide peptides) have been identified in representative species of
      gnathostomes. However, the identity of an LPXRFamide peptide had yet to be
      identified in agnathans, the most ancient lineage of vertebrates, leaving open
      the question of the evolutionary origin of GnIH and its ancestral function(s). In
      this study, we identified an LPXRFamide peptide gene encoding three peptides
      (LPXRFa-1a, LPXRFa-1b, and LPXRFa-2) from the brain of sea lamprey by synteny
      analysis and cDNA cloning, and the mature peptides by immunoaffinity purification
      and mass spectrometry. The expression of lamprey LPXRFamide peptide precursor
      mRNA was localized in the brain and gonad by RT-PCR and in the hypothalamus by in
      situ hybridization. Immunohistochemistry showed appositions of lamprey LPXRFamide
      peptide immunoreactive fibers in close proximity to GnRH-III neurons, suggesting
      that lamprey LPXRFamide peptides act on GnRH-III neurons. In addition, lamprey
      LPXRFa-2 stimulated the expression of lamprey GnRH-III protein in the
      hypothalamus and GTHbeta mRNA expression in the pituitary. Synteny and
      phylogenetic analyses suggest that the LPXRFamide peptide gene diverged from a
      common ancestral gene likely through gene duplication in the basal vertebrates.
      These results suggest that one ancestral function of LPXRFamide peptides may be
      stimulatory compared with the inhibitory function seen in later-evolved
      vertebrates (birds and mammals).

PMID- 22454149
TI  - Dietary vitamin D3 and 1,25-dihydroxyvitamin D3 (calcitriol) exhibit equivalent
      anticancer activity in mouse xenograft models of breast and prostate cancer.
AB  - 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3) or calcitriol], the hormonally active
      vitamin D metabolite, exhibits anticancer actions in models of breast cancer and
      prostate cancer. Because CYP27B1 (1alpha-hydroxylase), the enzyme catalyzing
      1,25(OH)(2)D(3) formation in the kidney, is also expressed in extrarenal tissues,
      we hypothesize that dietary vitamin D(3) will be converted to 25(OH)D(3) in the
      body and then to 1,25(OH)(2)D(3) locally in the cancer microenvironment in which
      it will exert autocrine/paracrine anticancer actions. Immunocompromised mice
      bearing MCF-7 breast cancer xenografts showed significant tumor shrinkage (>50%)
      after ingestion of a vitamin D(3)-supplemented diet (5000 IU/kg) compared with a
      control diet (1000 IU/kg). Dietary vitamin D(3) inhibition of tumor growth was
      equivalent to administered calcitriol (0.025, 0.05, or 0.1 MUg/mouse, three times
      a week). Both treatments equivalently inhibited PC-3 prostate cancer xenograft
      growth but to a lesser extent than the MCF-7 tumors. Calcitriol at 0.05 MUg and
      0.1 MUg caused modest but statistically significant increases in serum calcium
      levels indicating that the dietary vitamin D(3) comparison was to a maximally
      safe calcitriol dose. Dietary vitamin D(3) did not increase serum calcium,
      demonstrating its safety at the concentration tested. The vitamin D(3) diet
      raised circulating 1,25 dihydroxyvitamin D levels and did not alter CYP27B1 mRNA
      in the kidney but increased it in the tumors, suggesting that extrarenal sources
      including the tumors contributed to the elevated circulating 1,25
      dihydroxyvitamin D(3). Both calcitriol and dietary vitamin D(3) were equipotent
      in suppressing estrogen synthesis and signaling and other proinflammatory and
      growth signaling pathways. These preclinical data demonstrate the potential
      utility of dietary vitamin D(3) supplementation in cancer prevention and therapy.

PMID- 22454151
TI  - Habenular Kiss1 neurons modulate the serotonergic system in the brain of
      zebrafish.
AB  - The Kiss1/KISS1 gene has recently been implicated as a potent hypothalamic
      regulator of reproductive functions, in particular, the onset of puberty in
      mammals. In zebrafish (Danio rerio), there are two kiss1 homologues (kiss1 and
      kiss2) expressed in the brain: Kiss2-expressing neurons in the hypothalamic
      nuclei are considered potent regulators of reproduction, whereas the role of
      Kiss1-expressing neurons in the habenula remains unknown. We first analyzed the
      expression of kiss1 mRNA in a transgenic zebrafish, in which the habenula
      interpeduncular nucleus (IPN) pathway is labelled with green fluorescent protein,
      and our application of a biocytin neural tracer into the habenula showed the
      presence of neuronal projections of Kiss1 neurons to the ventral IPN. Therefore,
      we speculated that kiss1 neurons might regulate the serotonergic system in the
      raphe. However, laser microdissection followed by real-time PCR revealed the
      expression of Kiss1 receptor (kissr1) mRNA in the habenula and the ventral IPN
      but not in the dorsal IPN or the serotonergic neurons in the raphe nuclei. Dual
      fluorescent in situ hybridization revealed the coexpression of kiss1 and kissr1
      mRNA in the habenula. Administration of Kiss1 significantly decreased the level
      of kiss1 mRNA (0.3- to 0.5-fold, P < 0.001), but the level of c-fos mRNA was
      increased (~ 3-fold, P < 0.05) in the ventral habenula, suggesting that there is
      autocrine regulation of the kiss1 gene. Kiss1 administration significantly
      increased the c-fos mRNA levels in the raphe nuclei (2.5-fold, P < 0.001) and
      genes involved in the regulation of serotonin levels (pet1 and slc6a4a; 3.3- and
      2.2-fold, P < 0.01). These findings suggest that the autocrine-regulated
      habenular Kiss1 neurons indirectly regulate the serotonergic system in the raphe
      nuclei through the IPN in the zebrafish.

PMID- 22454152
TI  - Thyroid regeneration: characterization of clear cells after partial
      thyroidectomy.
AB  - Although having the capacity to grow in response to a stimulus that perturbs the
      pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ.
      In this study, partial thyroidectomy (PTx) was used to produce a condition for
      thyroid regeneration. In the intact thyroid gland, the central areas of both
      lobes served as the proliferative centers where microfollicles, and
      bromodeoxyuridine (BrdU)-positive and/or C cells, were localized. Two weeks after
      PTx, the number of BrdU-positive cells and cells with clear or faintly
      eosinophilic cytoplasm were markedly increased in the central area and continuous
      to the cut edge. Clear cells were scant in the cytoplasm, as determined by
      electron microscopy; some retained the characteristics of calcitonin-producing C
      cells by having neuroendocrine granules, whereas others retained follicular cell
      specific features, such as the juxtaposition to a lumen with microvilli. Some
      cells were BrdU-positive and expressed Foxa2, the definitive endoderm lineage
      marker. Serum TSH levels drastically changed due to the thyroidectomy-induced
      acute reduction in T(4)-generating tissue, resulting in a goitrogenesis setting.
      Microarray followed by pathway analysis revealed that the expression of genes
      involved in embryonic development and cancer was affected by PTx. The results
      suggest that both C cells and follicular cells may be altered by PTx to become
      immature cells or immature cells that might be derived from stem/progenitor cells
      on their way to differentiation into C cells or follicular cells. These immature
      clear cells may participate in the repair and/or regeneration of the thyroid
      gland.

PMID- 22454153
TI  - Developmental programming: prenatal and postnatal contribution of androgens and
      insulin in the reprogramming of estradiol positive feedback disruptions in
      prenatal testosterone-treated sheep.
AB  - Prenatal testosterone (T) excess compromises the estradiol (E(2)) positive
      feedback. This study tested the hypothesis that antagonizing androgen action or
      improving insulin sensitivity prenatally would prevent positive feedback
      disruptions from developing, whereas postnatal intervention with androgen
      antagonist or insulin sensitizer would ameliorate the severity of disruptions in
      prenatal T-treated females. The E(2) positive feedback response was tested at 16
      wk of age in the following groups of animals: 1) control, 2) prenatal T, 3)
      prenatal T plus the androgen antagonist, flutamide, 4) prenatal T plus insulin
      sensitizer, rosiglitazone, 5) prenatal T and postnatal androgen antagonist, and
      6) prenatal T and postnatal insulin sensitizer (n = 7-21 animals/group). Prenatal
      T treatment involved the administration of T propionate (100 mg, im) twice weekly
      from d 30 to 90 of gestation. Prenatal interventions involved daily sc
      administration of androgen antagonist (15 mg/kg) or oral administration of
      insulin sensitizer (8 mg) for the same duration. Postnatal treatments began at 8
      wk of age and involved daily oral administration of androgen antagonist (15
      mg/kg) or insulin sensitizer (0.11 mg/kg). None of the prenatal/postnatal
      interventions increased number of animals responding or prevented the time delay
      in LH surge response to the E(2) positive feedback challenge. In contrast, the
      postnatal treatment with androgen antagonist or insulin sensitizer increased
      total LH released in response to E(2) positive feedback challenge, compared with
      the T animals. Overall, these interventional studies indicate that timing and
      magnitude of the LH surge are programmed by different neuroendocrine mechanisms
      with postnatal androgens and insulin determining the size and prenatal estrogen
      likely the timing of the LH surge.

PMID- 22454155
TI  - Moral distress: a comparative analysis of theoretical understandings and inter
      related concepts.
AB  - Research on ethical dilemmas in health care has become increasingly salient
      during the last two decades resulting in confusion about the concept of moral
      distress. The aim of the present paper is to provide an overview and a
      comparative analysis of the theoretical understandings of moral distress and
      related concepts. The focus is on five concepts: moral distress, moral stress,
      stress of conscience, moral sensitivity and ethical climate. It is suggested that
      moral distress connects mainly to a psychological perspective; stress of
      conscience more to a theological-philosophical standpoint; and moral stress
      mostly to a physiological perspective. Further analysis indicates that these
      thoughts can be linked to the concepts of moral sensitivity and ethical climate
      through a relationship to moral agency. Moral agency comprises a moral awareness
      of moral problems and moral responsibility for others. It is suggested that moral
      distress may serve as a positive catalyst in exercising moral agency. An
      interdisciplinary approach in research and practice broadens our understanding of
      moral distress and its impact on health care personnel and patient care.

PMID- 22454154
TI  - Re-purposing cancer therapeutics for breast cancer immunotherapy.
AB  - After decades of work to develop immune-based therapies for cancer, the first
      drugs designed specifically to engage the host anti-tumor immune response for
      therapeutic benefit were recently approved for clinical use. Sipuleucel-T, a
      vaccine for advanced prostate cancer, and ipilimumab, a monoclonal antibody that
      mitigates the negative impact of cytotoxic T lymphocyte antigen-4 signaling on
      tumor immunity, provide a modest clinical benefit in some patients. The arrival
      of these drugs in the clinic is a significant advance that we can capitalize on
      for even better clinical outcomes. The strategic and scientifically rational
      integration of vaccines and other direct immunomodulators with standard cancer
      therapeutics should lead to therapeutic synergy and high rates of tumor
      rejection. This review focuses on the use of cyclophosphamide, doxorubicin, and
      HER-2-specific monoclonal antibodies to dissect mechanisms of immune tolerance
      relevant to breast cancer patients and illustrates how appropriate preclinical
      models can powerfully inform clinical translation. The immune-modulating activity
      of targeted, pathway-specific, small molecule therapeutics is also discussed.
      Fully understanding how cancer drugs impact the immune system should lead to the
      ultimate personalized cancer medicine: effective combinatorial immunotherapy
      strategies that simultaneously target signaling pathways essential for tumor
      growth and progression, and systematically break multiple, distinct immune
      tolerance pathways to maximize tumor rejection and effect cure.

PMID- 22454156
TI  - Cochlear implants in children younger than 6 months.
AB  - OBJECTIVES: (1) To determine the long-term outcomes of cochlear implantation in
      children implanted younger than 6 months and (2) to evaluate auditory-based
      performance in very young children compared with older children, all with
      profound sensorineural bilateral hearing loss. STUDY DESIGN: Prospective cohort
      study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Twelve subjects
      aged 2 to 6 months, 9 aged 7 to 12 months, 11 aged 13 to 18 months, and 13 aged
      19 to 24 months, all with profound bilateral hearing loss, were fitted with
      cochlear implants and followed longitudinally for 4 years. Subjects were
      developmentally normal with no additional disabilities (visual, motor, or
      cognitive). Auditory-based communication outcomes included tests for speech
      perception, receptive language development, receptive vocabulary, and speech
      production. RESULTS: Age at cochlear implantation was a significant factor in
      most outcome measures, contributing significantly to speech perception, speech
      production, and language outcomes. There were no major complications and no
      significantly higher rates of minor complications in the younger children.
      CONCLUSION: This article reports an uncontrolled observational study on a small
      group of infants fitted with cochlear implants following personal audiological
      criteria and, up to now, with limited literature support due to the innovative
      nature of the study. This study shows, for the first time, significantly improved
      auditory-based outcomes in children implanted younger than 6 months and without
      an increased rate of complications. The data from the present study must be
      considered as explorative, and a more extensive study is required.

PMID- 22454157
TI  - [Strategy for better combination of targeted therapy and surgery in the treatment
      of gastrointestinal stromal tumor].
AB  - For primary localized gastrointestinal stromal tumor(GIST), complete resection
      followed by imatinib adjuvant therapy has become a consensus among physicians for
      median and high risk patients. Preoperative imatinib may decrease surgical
      morbidity, increase resection rate, and even preserve organ function through down
      staging of the tumor. For advanced GIST, the choice of treatment is targeted
      therapy with tyrosine kinase inhibitor. Although surgical intervention showed
      certain efficacy in several retrospective analyses, the role of surgery for
      advanced disease still needs to be proven by prospective controlled trials.
      Better combination of targeted therapy and surgery has become critical in
      multidisciplinary therapy for GIST.

PMID- 22454158
TI  - [Challenges of gastrointestinal stromal tumor in the era of targeted therapy].
AB  - Targeted drugs has improved the overall survival of patients with
      gastrointestinal stromal tumor (GIST). However, there are some difficulties and
      controversies. Imatinib adjuvant therapy improves recurrence-free survival, but
      the treatment duration has not been determined. Furthermore, whether adjuvant
      therapy is beneficial to the GIST with c-kit exon 9 mutation and wild type is
      unclear. There are currently no prospective randomized controlled trials on the
      role of combination of surgery with tyrosine kinase inhibitor in patients with
      metastatic GIST. In addition, many challenging issues remain to be solved
      including patients education, side effect monitoring during sunitinib treatment,
      the influence of difference between the Eastern patients and the Western
      counterparts on sunitinib treatment schedule, and the choice of regimen after
      imatinib and sunitinib failure, etc. Difficulties exist in the discovery of new
      targets in the downstream of kit gene and the concurrent use of multiple targeted
      drugs. This article analyzes these problems in order to achieve a consensus and
      discuss future directions.

PMID- 22454159
TI  - [Imaging evaluation of targeted therapy for gastrointestinal stromal tumor].
AB  - Imaging study is the primary method to evaluate the efficacy of targeted therapy
      for gastrointestinal stromal tumor(GIST). The application of RECIST morphological
      criteria has limitations in the evaluation of targeted therapy, which may result
      in incorrect reflection of responses by conventional size-based criteria. Recent
      proposed Choi criteria, which combined the size and the CT value, has extended
      the application of radiology in the evaluation of GIST. The early change of
      apparent diffusion coefficient(ADC) values on diffusion-weighted imaging(DWI) can
      reflect the response of GIST to targeted therapy. The prominent change of ADC can
      be detected within one week after therapy. Through comprehensive analysis of the
      imaging characteristics associated with the biological behavior of GIST, new
      approaches may be developed in the evaluation of response of GIST to targeted
      therapy.

PMID- 22454160
TI  - [Strategies in diagnosis and management for advanced or metastatic
      gastrointestinal stromal tumor].
AB  - With deeper understanding of gastrointestinal stromal tumor(GIST), more and more
      patients are diagnosed as GIST. Although the prognosis of early GIST is
      satisfactory after complete surgical resection, there are still many problems in
      the treatment of advanced GIST. Variety of treatment options has been used in the
      treatment of GIST, such as surgery, targeted drug therapy, and surgery plus
      imatinib therapy. However, post-operative recurrence, imatinib-resistance, multi
      targeted drug resistance are still challenges. Many clinical evidences show that
      a reasonable management strategy can improve the prognosis of patients with
      advanced GIST. All the doctors should have a clear mind to carry out appropriate
      interventions. Advanced GIST should not be simply considered to be either medical
      or surgical disease, but rather must be systematically managed by
      multidisciplinary team approach combining surgical oncology, medical oncology,
      pathology, and interventional medicine. This review will advocate suitable
      treatment strategies based on the most recent progresses in systemic treatment
      for advanced GIST and our clinical experience to achieve early detection, early
      prevention, proper management, and therefore improve the survival of these
      patients.

PMID- 22454161
TI  - [Feasibility of endoscopic resection for gastric gastrointestinal stromal tumor].
AB  - In recent years, with the development of digestive endoscopy, endoscopic
      submucosal dissection(ESD) and its derived techniques including endoscopic
      submucosal excavation(ESE), submucosal tunnelling endoscopic resection(STER) and
      laparoscopic endoscopic combined surgery(LECS), can cure most of the gastric
      gastrointestinal stromal tumor(GIST). This article reviews the indication, method
      and evaluation of endoscopic resection for gastric GIST.

PMID- 22454162
TI  - [Management of liver metastases of gastrointestinal stromal tumor].
AB  - Liver is the most common metastatic site of gastrointestinal stromal tumor(GIST).
      The recurrence rate is high even after hepatectomy. Although tyrosine kinase
      inhibitors (TKI) makes the resection feasible for some of the liver metastasis of
      GIST and significantly increase the overall survival, surgery still can not be
      substituted. Therefore, it is worth investigating and exploring the most
      appropriate treatment for the GIST with liver metastasis.

PMID- 22454163
TI  - [Treatment of recurrent or metastatic gastrointestinal stromal tumor: surgery or
      not].
AB  - Currently, the treatment of recurrent or metastatic gastrointestinal stromal
      tumor(GIST) has become a tremendous challenge. Some international clinical trials
      revealed that imatinib might significantly improve the survival of patients with
      recurrent or metastatic GIST. Though the combination of surgery and imatinib has
      become an ideal treatment of metastatic GIST, there still exist some
      controversies regarding how to combine the two methods. Imatinib may influence
      the blood coagulation mechanism, therefore it is suggested that imatinib
      cessation should be performed a week before operation. Cytoreductive surgery has
      some clinical effects on recurrent or metastatic GIST, which can be combined with
      targeted therapy. Furthermore, the clinical trial for recurrent or metastatic
      GIST needs further evaluation.

PMID- 22454164
TI  - [Consideration on relative issues of gastrointestinal stromal tumor].
AB  - Nowadays one of the hot research topics in gastrointestinal surgery is
      gastrointestinal stromal tumor (GIST). However, mechanisms of their formation and
      development, and the causes of recurrence following R0 resection, have not been
      fully understood. This article aims to investigate some important issues
      concerning the neoplastic essences of GIST including the genomics, bionomics,
      drug resistance and immunotherapy.

PMID- 22454165
TI  - [Value and application of multidisciplinary modality in the diagnosis and
      treatment of gastrointestinal stromal tumor].
AB  - Treatment of cancer has evolved from surgical intervention towards
      multidisciplinary team(MDT) approach. The effect of MDT treatment modality on
      cancer is significantly better than that of conventional treatment modality.
      Obvious achievements have been made in breast cancer, colorectal cancer, and
      gastric cancer using the MDT model. Gastrointestinal stromal tumor(GIST) is the
      most common mesenchymal tumor of the gastrointestinal tract. With the success  in
      GIST, molecular targeted therapy has become more and more specialized and
      individualized to manage this tumor. MDT modality is especially important in the
      diagnosis and treatment of GIST.

PMID- 22454166
TI  - [To emphasize the importance of specimen fixation and improve quality of
      diagnosis of gastrointestinal stromal tumor].
AB  - The most common problem in the diagnosis of gastrointestinal stromal tumor (GIST)
      is inadequate specimen fixation. The paper focused on specimen fixation and
      standardized protocol in immunohistochemistry staining and gene mutation
      detection. We have adjusted some procedure used in immunohistochemistry staining
      and c-kit gene detection to improve the quality of inadequately fixed specimen.
      It maybe useful for clinicians, pathologists and technicians working in
      immunohistochemistry labs and gene detection labs.

PMID- 22454167
TI  - [Therapeutic value of endoscopic submucosal dissection for gastrointestinal
      stromal tumor in the esophagogastric junction].
AB  - OBJECTIVE: To evaluate the safety and efficacy of endoscopic submucosal
      dissection (ESD) for gastrointestinal stromal tumor(GIST) in the esophagogastric
      junction(EGJ). METHODS: Twenty patients with pathologically confirmed GIST in the
      EGJ were screened from all the patients undergoing ESD between November 2007 and
      June 2011. The clinicopathological and postoperative follow up data were
      analyzed. RESULTS: There were 11 males and 9 females with the age ranging from 29
      to 67 years(mean, 54.1 years). The maximum diameter of the lesions ranged from 8
      to 20 mm(mean,14.8 mm). Fifteen patients underwent endoscopic submucosal
      excavation, 4 patients underwent endoscopic full-thickness resection, and 1
      patient underwent submucosal tunneling endoscopic resection. The operative time
      ranged from 15 to 90 min(mean, 47.8 minutes). The estimated blood loss was 5 to
      200 ml. The en bloc resection rate was 100%. Perforations occurred in 4 patients,
      pneumoperitoneum in 3 patients, cardia mucosal tear in 1 patient. All the
      complications were successfully managed with endoscopic intervention and
      conservative therapy. The post-operative follow up ranged from 3 to 36
      months(mean, 13.2 months). No local recurrence or distant metastasis occurred.
      CONCLUSION: ESD is a safe and effective procedure for GIST in the EGJ.

PMID- 22454168
TI  - [Clinical analysis of laparoscopic and endoscopic cooperative surgery in the
      treatment of gastric gastrointestinal stromal tumor: report of 46 cases].
AB  - OBJECTIVE: To evaluate the feasibility and safety of laparoscopic and endoscopic
      cooperative surgery for treating gastric gastrointestinal stromal tumors(GIST).
      METHODS: Retrospective analysis was performed on the clinical data of 46 patients
      with gastric GIST undergoing laparoscopic and endoscopic cooperative surgery
      between June 2009 and June 2011 at the Renji Hospital of Shanghai Jiaotong
      University School of Medicine. RESULTS: There were 27 males and 19 females with
      the mean age of 58.5 years. Thirty-three patients received endoscopy-assisted
      wedge resection, and 13 cases received laparoscopy-assisted endoscopic resection.
      All the operations were successful. The mean operative time was (85.5+/-29.3)
      min, the mean blood loss was (31.4+/-12.2) ml, the mean post-operative
      gastrointestinal functional recovery time was (31.6+/-14.9) h, and the mean post
      operative hospital stay was (5.1+/-2.9) d. No post-operative complication
      occurred. NIH risk assessment showed that 34 cases were very low risk and 12 low
      risk. No recurrence or metastasis was found during the follow-up ranging from 2
      to 26 months(median, 12.6 months). CONCLUSION: Laparoscopic and endoscopic
      cooperative surgery for gastric GIST is both feasible and safe with minimal
      invasiveness, fast recovery and satisfactory short-term outcomes.

PMID- 22454169
TI  - [Clinical analysis of imatinib in patients with advanced gastrointestinal stromal
      tumor].
AB  - OBJECTIVE: To evaluate the efficacy and influencing factors of imatinib in
      patients with advanced gastrointestinal stromal tumor(GIST). METHODS: From April
      2004 to January 2010, clinicopathological data of 73 adult patients with advanced
      GIST treated with imatinib at the First Affiliated Hospital of Sun Yat-sen
      University were retrospectively analyzed. The treatment outcomes and associated
      factors were investigated. RESULTS: Treatment outcomes included complete response
      in 1(1.4%) patients, partial response in 53(72.6%), stable disease in 14(19.2%),
      and primary resistant in 5(6.8%). All the patients had routine followed up, the
      length of which ranged from 12 to 76 (median 32) months. The median progression
      free survival was 45.0 months(95% confidence interval, 34.2-55.8). The
      progression-free survival(PFS) rate was 87.7% in 1 year, 63.6% in 3 year, and
      39.6% in 5 years. On multivariate analysis, both mutation status and patient
      performance were independent factors influencing the efficacy of imatinib
      treatment(both P<0.01). PFS was significantly better in patients with c-kit exon
      11 mutations than those with exon 9 mutations, and better in lower ECOG scales
      than in higher ones. CONCLUSION: Imatinib is effective in treating patients with
      advanced GIST, c-kit exon 9 mutations and poor performance status predict an
      adverse survival benefit of imatinib therapy.

PMID- 22454170
TI  - [Clinicopathologic features and prognostic factors of gastric gastrointestinal
      stromal tumor with synchronous gastric cancer].
AB  - OBJECTIVE: To evaluated the clinicopathologic features and prognostic factors of
      gastric gastrointestinal stromal tumor(GIST) with synchronous gastric cancer.
      METHODS: The clinicopathologic records of 122 patients with gastric GIST who
      underwent surgical treatment from April 2000 to June 2010 were analyzed
      retrospectively. Twenty-six patients presented synchronous gastric cancer(group
      A), while 96 patients did not(group B). The clinicopathologic features of gastric
      GIST were compared between the two groups. Potential prognostic factors were
      evaluated by univariate and multivariate analyses. RESULTS: Gastric GIST in group
      A were associated with smaller tumor diameter (P<0.01), lower mitotic
      count(P<0.05), lower Fletcher classification(P<0.01), and lower rate of pre
      operative diagnosis(23.1% vs. 97.9%, P<0.01). On univariate analysis, maximum
      tumor diameter (P<0.01), mitotic count (P<0.01), Fletcher classification (P<0.01)
      and synchronous gastric cancer(P<0.05) were the predictive factors of survival.
      Multivariate analysis showed that Fletcher classification(P<0.05) and synchronous
      gastric cancer (P<0.01) were independent prognostic factors. CONCLUSIONS: In
      patients with synchronous gastric GIST and gastric cancer, Fletcher
      classification of GIST is usually very low or low invasion risk and has minimal
      impact on the prognosis. Survival depends primarily on the gastric cancer.

PMID- 22454171
TI  - [Clinical analysis of 217 patients with gastrointestinal stromal tumor].
AB  - OBJECTIVE: To study the clinical characteristics, diagnosis, treatment and
      prognostic factors of gastrointestinal stromal tumor(GIST). METHODS:
      Clinicopathological data of 217 GIST patients from January 2005 to September 2010
      in Wuhan Union Hospital were analyzed retrospectively and the prognostic factors
      were evaluated. RESULTS: There were 103 males and 114 females with a median age
      of 55 years old. Two hundred and thirteen patients underwent R0 resection and 4
      R1 resection due to extensive invasion. Thirty-five patients underwent
      laparoscopic resection. Forty-eight patients received imatinib mesylate therapy
      after surgery. A total of 178 patients(82.0%) were followed up for 3 to 74
      months. Sixteen patients(9.0%) developed recurrence or metastasis. Logistic
      regression analysis showed that tumor location (OR=2.547, 95% CI:1.466-4.424) and
      mitotic count(OR=6.556, 95% CI:2.974-14.449) were independent factors for post
      operative recurrence or metastasis. Five patients survived with tumor, and 11
      patients(6.2%) died of GIST including intestinal GIST(n=7) and extraintestinal
      GIST(n=4). Cox regression analysis showed that the mitotic count (RR=2.654, 95%
      CI:1.094-6.438) and post-operative recurrence or metastasis (RR=32.988, 95%
      CI:3.879-280.529) were independent prognostic factors. CONCLUSIONS: Tumor
      location and mitotic count are independent risk factors for post-operative
      recurrence or metastasis in GIST. Mitotic count and post-operative recurrence or
      metastasis are independent indicators of poor prognosis. Surgical radical
      resection combined with targeted therapy can achieve satisfactory outcomes in
      patients with GIST.

PMID- 22454172
TI  - [Prognosis analysis of 216 cases of gastrointestinal stromal tumor].
AB  - OBJECTIVE: To analyze the impact of location of gastrointestinal stromal
      tumor(GIST) on the survival, and the influence of surgical treatment and imatinib
      therapy on survival. METHODS: The clinical data of 216 patients with GIST who
      were admitted to the People's Liberation Army Hospital from January 2004 to
      December 2010 were analyzed retrospectively. RESULTS: All the patients were
      followed up with a median time of 22 months(1 to 83 months). The 1-, 3-, and 5
      year survival rates were 93%, 75% and 30%. The survival rates of 5-year with GIST
      located in the stomach (103 cases), the small intestine (45 cases) and
      gastrointestinal outside(41 cases) were 93%, 75%, and 30%, respectively, and the
      differences were statistically significant(P<0.05). There were no deaths in
      patients with GIST located in duodenum(18 cases) and rectum(9 cases). The 5-years
      survival rates of GIST in the groups of complete excision combined with imatinib,
      complete resection without imatinib, incomplete resection combined with imatinib,
      incomplete resection without imatinib were 100%, 98%, 49% and 14%, respectively,
      and the differences were statistically significant(P<0.05). CONCLUSIONS: GISTs in
      different parts of gastrointestinal tract have different survival rates. Radical
      resection and imatinib can improve the survival rates of patients with GIST.

PMID- 22454173
TI  - [Treatment and prognosis of gastrointestinal stromal tumor in small intestine: an
      analysis of 64 patients].
AB  - OBJECTIVE: To investigate treatment and prognostic factors of gastrointestinal
      stromal tumor(GIST) in the small intestine. METHODS: The clinicopathological data
      of 64 patients with GIST in the small intestine admitted to the Tianjin Medical
      University Affiliated Cancer Hospital between April 2002 and November 2010 were
      analyzed retrospectively and the prognostic factors were evaluated. RESULTS: No
      patients in this cohort received chemotherapy or radiation therapy. Fourteen
      patients underwent post-operative imatinib targeted therapy. The overall 5-year
      survival rate was 51.2% and the post-operative recurrence rate of 61 cases
      undergoing R0 resection was 44.3%. Univariate analysis revealed that the complete
      tumor resection(P=0.001), tumor size(P=0.018), adhesion or invasion to
      surrounding tissue and organs (P=0.015), concurrent distant metastasis(P=0.000),
      tumor hemorrhage (P=0.032), Fletcher classification (P=0.027) and
      symptom(P=0.012) were associated with prognosis. Multivariate analysis
      demonstrated that adhesion or invasion to surrounding tissue and organs(P=0.026),
      concurrent distant metastasis(P=0.000) and symptom(P=0.019) were independent
      prognostic factors for survival. CONCLUSION: The survival evaluation of patients
      with small intestinal GIST depends on surgery, tumor size, adhesion or invasion
      to surrounding tissue and organs, concurrent distant metastasis, tumor
      hemorrhage, symptom, Fletcher classification, and use of targeted therapy.

PMID- 22454174
TI  - [Prognostic analysis of 40 cases with rectal gastrointestinal stromal tumor].
AB  - OBJECTIVE: To analyze the prognosis of rectal gastrointestinal stromal tumors
      (GIST). METHODS: Records of 40 patients diagnosed as rectal GIST at the
      Affiliated Chinese Traditional Medical Hospital of Xinjiang Medical University
      and the People's Hospital of Tianjin City between June 1979 and June 2010 were
      reviewed. Clinical features, treatment modalities and outcomes were analyzed.
      RESULTS: There were 23 males and 17 females with a median age of 54.5 years old
      (range, 28-81 years old). During the follow-up(median 52.5 months, range 1-300
      months), 18 patients developed recurrence including 7 local recurrence, 6
      metastasis and 5 local recurrence complicated with metastasis. The overall
      survival rates at 1, 3 and 5 years were 82.5%, 60.0%, and 42.5% respectively. On
      univariate analysis, tumor size(P<0.01), Fletcher classification(P<0.01), mitotic
      index(P<0.01), and post-operative distant metastasis were associated with
      survival. Multivariate analysis showed that tumor size(P<0.05), mitotic rate
      (P<0.01), and postoperative distant metastasis(P<0.01) were independent
      prognostic factors associated with survival. CONCLUSIONS: Surgery is the main
      treatment for rectal GIST. Tumor size, mitotic rate and metastasis are
      independent prognostic factors in patients with rectal GIST.

PMID- 22454175
TI  - [Therapeutic effect of in vitro 5-aza-2'-deoxycytidine combined with imatinib on
      gastrointestinal stromal tumor].
AB  - OBJECTIVE: To investigate the impact of 5-aza-2'-deoxycytidine(5-aza-CdR)
      combined with imatinib on the proliferation, motility, invasion, and apoptosis of
      gastrointestinal stromal tumors(GIST) cells in vitro. METHODS: MTT assay was used
      to investigate the effect of the two agents on proliferation of GIST882. Plate
      colony forming assay was used to determine the number of colony-forming. Motility
      and invasion abilities were tested to evaluate the inhibitory effect of each
      agent. Flow cytometry was used to observe apoptosis and cell cycle. RESULTS: 5
      aza-CdR or imatinib effectively inhibited the growth of GIST882 cells in
      concentration- and time-dependent manner. The inhibitory rate of combined
      treatment using 5-aza-CdR and imatinib was significantly higher than that of 5
      aza-CdR or imatinib alone(P<0.05). After treatment for 48 h, the apoptosis rates
      of 5-aza-CdR group (1000 MUg/L) and imatinib group (100 MUmol/L) were (11.7+/
      1.2)% and (14.6+/-0.8)%, respectively. Compared with the control group (2.8+/
      0.3)%, the difference was statistically significant(P=0.000). Furthermore, the
      difference in apoptosis rate was significant between combined treatment group
      (19.4+/-1.1)% and single drug treatment group(vs. 5-aza-CdR group, P=0.000, vs.
      imatinib group, P=0.013). 5-aza-CdR raised G0/G1 ratio and reduced S ratio of
      GIST882. Imatinib and combined group had no apparent influence on the cell cycle
      of GIST882 cells. CONCLUSION: 5-aza-CdR may be a potential agent of GIST
      treatment in the near future.

PMID- 22454176
TI  - [Relationship of c-kit and platelet-derived growth factor receptor alpha gene
      mutation features with prognosis of patients with gastrointestinal stromal
      tumor].
AB  - OBJECTIVE: To explore the relationship between c-kit and platelet-derived growth
      factor receptor alpha(PDGFRA) gene mutation features and the prognosis of
      gastrointestinal stromal tumor(GIST). METHODS: Clinicopathological, genetic
      testing and follow-up informations of patients admitted to the Shanxi Tumor
      Hospital from June 2000 to January 2009 were collected. The survival was
      calculated and univariate analysis was conducted using the Kaplan-Meier method.
      Multivariate analysis was conducted by the Cox regression method. RESULTS: The 5
      year disease-free survival rate was 61.5% and the 5-year overall survival rate
      was 67.4%.  The 5-year disease-free survival rates of patients without disease
      among those with c-kit exon 11 mutation (n=77), c-kit exon 9 mutation(n=4), and
      PDGFRA exon 18 mutation (n=2) were 63.4%, 14.3% and 100%, and the 5-year overall
      survival rates were 70.8%, 50.0% and 100%, respectively. In the patients with c
      kit exon 11 mutation, the 5-year disease-free survival rates among those with
      point mutations(n=26), deletion mutations(n=44), and duplication mutations(n=7)
      were 87.1%, 44.9% and 80.0%, and the 5-year overall survival rates were 88.1%,
      57.0% and 100%, respectively. There were significant differences in overall
      survival among different factors. Multivariate analysis showed that gene mutation
      was not the independent factor of prognosis(P=0.492). CONCLUSIONS: In GIST
      patients undergoing surgery without imatinib treatment, mutated genotype is
      better than wild type in terms of prognosis. Gene mutation is not the independent
      factor of prognosis in GIST patients.

PMID- 22454177
TI  - [Prevention strategy of post-operative complications in elderly patients with
      colorectal cancer based on scoring systems].
AB  - OBJECTIVE: To explore the risk factors and prevention strategies of post
      operative complications in elderly patients with colorectal cancer. METHODS: Data
      of 107 elderly patients (>=75 years) undergoing surgery for colorectal cancer
      were collected from January 2006 to December 2009 in the Department of
      Gastrointestinal Surgery, Peking University People's Hospital. POSSUM and E
      POSSUM scoring systems were used to predict post-operative complications. ROC
      curve and observe/expect(O/E) were used to assess the validity of scoring
      systems. Logistic regression was used to evaluate the independent risk factors
      associated with post-operative complications of elderly patients with colorectal
      cancer. RESULTS: The predictive  complication rates of E-POSSUM and POSSUM in
      elderly patients with colorectal cancer were 13.9%-86.6%(average, 32.7%) and
      19.1%-99.1% (average, 55.5%). The predictive validity of E-POSSUM was better than
      POSSUM(AUC of ROC: 0.862 vs. 0.576, O/E: 0.771 vs. 0.454), the former was closer
      to the actual complication rate(25.2%, 27/107). Concurrent diabetes
      mellitus(P=0.019) and rectal lesion(P=0.005) were independent risk factors
      associated with surgery-related post-operative complications. Anastomotic leakage
      was the most common surgery-related post-operative complications. Chronic
      obstructive pulmonary disease(P=0.026), ASA score(P=0.025), intestinal
      obstruction(P=0.037) and perforation(P=0.001) were independent risk factors
      associated with non-surgery-related post-operative complications. Pulmonary
      infection was the most common non-surgery-related post-operative complication.
      CONCLUSIONS: The application of E-POSSUM scoring system can provide more accurate
      prediction of post-operative complications in elderly patients undergoing surgery
      for colorectal cancer. Positive interventions should be taken for high-risk
      patients to prevent post-operative complications.

PMID- 22454178
TI  - [Complete closure of gastric wall defect after endoscopic full-thick resection
      with metal clips and endoloop snare].
AB  - OBJECTIVE: To study the value of the metal clips and endoloop snare for gastric
      wall defect after endoscopic full-thick resection(EFR). METHODS: All the patients
      who underwent complete closure of gastric wall defect after endoscopic full-thick
      resection with metal clips and endoloop snare in the Endoscopy Center of
      Zhongshan hospital from March 2011 to October 2011 were retrospectively studied.
      The feasibility, safety, and efficacy were evaluated. RESULTS: Fourteen patients
      were included in this study. The median age was 49(32-63) years. Lesions located
      in the gastric body in 5 cases, the gastric fundus in 8 cases, and the gastric
      antrum and body junction in 1 case. The were diameter was 0.6-3.0 cm. Complete
      closure rate was 100% using this technique. The median repair time was 12(8-20)
      min. No patients were converted to surgery or laparoscopic surgery. Four patients
      complained of abdomen pain with elevated body temperature, and ultrasonography
      showed minor peritoneal fluid in 2 cases, which were drained. These four cases
      were asked to maintain semi-reclining position and were put on fasting,
      continuous gastrointestinal decompression, and received antibiotics. They were
      discharged after 1-3 days. All the patients were followed up with a median time
      of 3(1-8) months. Nylon and clips residual were removed endoscopically and the
      wound healing was satisfactory. CONCLUSION: Metal clips and endoloop snare is
      safe and effective for the closure of gastric wall defect after EFR.

PMID- 22454179
TI  - [Delorme procedure for full-thickness rectal prolapse: a report of 25 cases].
AB  - OBJECTIVE: To evaluate the use of Delorme procedure for full-thickness rectal
      prolapse. METHODS: A series of 25 patients with full-thickness rectal prolapse
      were treated by Delorme procedure in four institutions between March 2005 and
      June 2010. The clinicopathological data were analyzed retrospectively. RESULTS:
      There were 9 males and 16 females. The mean age was 52(46-72) years old. All the
      procedures were successfully performed. There were no perioperative deaths. The
      mean operative time was 65(45-150) min. The intraoperative bleeding was 58(20
      200) ml. The mean length of hospital stay was 8.5(5-14) days. Anastomosis
      dehiscence occurred in 1 patient at post-operative day 7 who was managed under
      anesthesia. Minor complications occurred in 8(32%) patients, including urinary
      retention(n=3), intractable pain(n=1), and bowel obstruction(n=4). The follow up
      time ranged from 2 to 6 years with a median of 3.5 years. Prolapse recurrence was
      observed in 1(4%) patient during the follow up. The remission rates of fecal
      incontinence, constipation, bleeding were 37.5%(6/16), 45.5%(5/11), and
      15.4%(2/11), respectively. The Wexner incontinence score significantly decreased
      (median, 5.0 vs. 9.0, P<0.01). The resting pressure and maximum squeeze pressure
      increased significantly after surgery, while the initial volume and maximal
      tolerance volume decreased significantly(All P<0.01). CONCLUSIONS: Delorme
      procedure is safe and easy to perform. The anorectal function is improved after
      surgery. Therefore it should be considered the procedure of choice for rectal
      prolapsed.

PMID- 22454180
TI  - [Long non-coding RNA influences radiosensitivity of colorectal carcinoma cell
      lines by regulating cyclin D1 expression].
AB  - OBJECTIVE: To screen long non-coding RNA which influences radiosensitivity of
      colorectal carcinoma cell lines and investigate the mechanism. METHODS: Under
      different doses of radiation, colony formation assay and single-hit multi-target
      model were conducted to draw dose-survival curve and SF2 value of colorectal
      carcinoma cell lines(RKO, Lovo) was calculated. High-throughput lncRNA/mRNA chips
      were used to screen lncRNA genes and protein coding genes with expression
      differences more than 2 folds between RKO, Lovo cell lines and RKO cell line
      receiving 2Gy radiation. The main action pathway was computed by Gene Ontology
      analysis combined with Pathway analysis in order to explore the mechanism which
      induces the effect of lncRNA on radiosensitivity of colorectal carcinoma cell
      lines. Further experiment on P53, P21, cyclin D1 expression contents of RKO cell
      line was confirmed by real-time RT-PCR. RESULTS: Lovo(SF2=0.47) was more
      sensitivity to radiation than RKO(SF2=0.53) according to the outcome of colony
      formation assay. High-throughput lncRNA/mRNA chips identified a total of 268
      lncRNA genes and 270 protein coding genes. Gene Ontology analysis showed that the
      expression of genes associated with cell cycle process were significantly
      different (38.6%). There was a significant relationship between expression of
      several lncRNAs and CCND1 gene. Real-time RT-PCR showed no significant
      differences of P53 and P21 expression in RKO and Lovo cell lines(P>0.05), while
      cyclin D1 expression of RKO cell line was higher than that of Lovo cell
      lines(P<0.05). After exposed to 2 Gy doses of radiation, there was an obvious
      decrease of cyclin D1 expression in RKO cell lines(P<0.05), while P53 and P21
      expressions were not different(P>0.05). CONCLUSION: The possible mechanism is
      that lncRNAs compose transcription compound to combine with CCND1 gene and
      influence radiosensitivity of colorectal carcinoma cell lines by regulating
      expression of cyclin D1, which is independent of P53-P21-cyclin D1 pathway.

PMID- 22454181
TI  - [Anti-tumor effect of adenovirus-mediated Bcl-XL shRNA in vitro].
AB  - OBJECTIVE: To investigate the anti-tumor effect of adenovirus-mediated Bcl-XL
      shRNA on colon cancer cells in vitro. METHODS: A recombinant Bcl-xl adenovirus
      was constructed, amplified, and purified. The effect on mRNA expression of Bcl-XL
      was assessed by RT-PCR, and the effect on apoptosis-induction of colon
      cancer(Lovo cell line) in vitro was assessed by MTT assay and cell clonogenic
      assay. RESULTS: RT-PCR showed that Ad/Bcl-XL shRNA significantly down-regulated
      the mRNA expression of Bcl-XL in Lovo cells. Ad/Bcl-XL shRNA suppressed the
      proliferation of Lovo cells in a dose-dependent as well as a time-dependent
      manner compared with Ad/GFP (P<0.05). Treatment with Ad/Bcl-XL shRNA dramatically
      suppressed the colony formation of Lovo cells in a dose-dependent manner
      (P<0.05). Ad/Bcl-XL shRNA showed no effect on normal human fibroblast.
      CONCLUSION: Ad/Bcl-XL shRNA exhibits cytotoxic effect on Lovo cells and may have
      the potential value in the treatment of colon cancer.

PMID- 22454182
TI  - [Resistance and treatment strategy of gastrointestinal stromal tumor target
      therapy].
AB  - Gastrointestinal stromal tumor(GIST) originates from interstitial cells of
      Cajal(ICCs). Tyrosine kinase inhibitors(TKI) such as imatinib and sunitinib, are
      effective agents besides surgery. However some GIST can become primarily or
      secondarily resistant to those drugs. The difference in gene mutation types and
      secondary gene mutation is the main cause. When the GIST is proved to be drug
      resistance, reasonable personal treatment strategies based on individualized
      medicine should be made to improve outcomes and quality of life.

PMID- 22454183
TI  - Comparing vertebral body reconstruction implants for the treatment of thoracic
      and lumbar metastatic spinal tumors: a consecutive case series of 37 patients.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To compare different
      interbody reconstruction implants after corpectomy in metastatic spine tumors.
      SUMMARY OF BACKGROUND DATA: Vertebral body reconstruction after corpectomy is
      common for patients with metastatic spine tumors. Although various implants are
      reported individually in the literature, no study to-date has compared them with
      one another directly. METHODS: Thirty-seven consecutive patients with metastatic
      tumors of the thoracic or lumbar spine underwent single or multilevel corpectomy
      with subsequent interbody reconstruction. Longevity of interbody graft was
      primarily evaluated in this study as defined by the need for any revision
      surgeries or complications after surgery. Data was collected retrospectively.
      RESULTS: Twenty-seven, 5, and 5 patients underwent reconstruction with metal
      implants, bone implants, and polymethylmethacrylate (PMMA), respectively. Twenty
      three patients had metastatic tumor involvement of the thoracic spine and 14
      patients had tumor involvement of the lumbar spine. Three patients (8.1%)
      required additional surgery: 1 wound infection, 1 hardware revision, and 1 for
      resection of an intradural, intramedullary tumor not identified at the first
      operation. Overall complication rate was 43.2% (16 patients) and 2 patients died
      within 30 days of their index spine surgery. Postoperative complication rates
      were more than double in the metal implant group (52%) compared with an equal
      number of complications in bone (20%) and PMMA (20%) implant group. The rate of
      revision surgery was highest in the bone group (40%) compared with none in the
      PMMA and only 3.7% in the metal interbody groups. CONCLUSIONS: Vertebral body
      reconstruction after corpectomy for patients with metastatic tumors to the
      thoracic and lumbar spine can be performed effectively with metal, bone, or
      cement implants. Although metal implants are used in the majority of
      reconstruction cases, they seem to have a higher rate of overall complications,
      with bone interbody constructs showing a higher rate of revision surgery.

PMID- 22454184
TI  - Investigation of segmental motor paralysis after cervical laminoplasty using
      intraoperative spinal cord monitoring with transcranial electric motor-evoked
      potentials.
AB  - STUDY DESIGN: A retrospective study of segmental motor paralysis after cervical
      laminoplasty for cervical myelopathy. OBJECTIVE: The objective of this study was
      to use transcranial electric motor-evoked potentials during cervical
      laminoplasty, to monitor and investigate the intraoperative electrophysiologic
      change in patients with cervical myelopathy, who subsequently develop
      postoperative segmental motor paralysis potentials. SUMMARY OF BACKGROUND DATA:
      There have been several reports about segmental motor paralysis after cervical
      laminoplasty for patients with cervical myelopathy. However, the pathogenesis of
      segmental motor paralysis of C5 myotome, so-called C5 palsy, remains unclear.
      METHODS: The cases of 184 consecutive patients who underwent cervical
      laminoplasty were analyzed to clarify the incidence of postoperative segmental
      motor paralysis and to monitor intraoperative change. Postoperative C5 palsy was
      defined as development of postoperative motor palsy of the deltoid and biceps
      muscles in the upper extremity by at least 1 grade in the manual muscle test
      without sensory disturbance or impairment of the lower extremities. All patients
      underwent cervical laminoplasty under intraoperative spinal cord monitoring with
      transcranial electric motor-evoked potentials. The evoked potentials were
      recorded over the deltoid, biceps, and triceps muscles in the bilateral upper
      extremities. RESULTS: Postoperative C5 palsy developed in 6 patients (3.3%, 5
      males and 1 female) but there were no abnormal changes monitored. The incidence
      of C5 palsy involved 4 of 124 (3.2%) cervical spondylotic myelopathy patients, 2
      of 31 (6.5%) patients with cervical ossification of the posterior longitudinal
      ligament. No patients with cervical disc herniation or cervical spondylotic
      amyotrophy developed C5 palsy. CONCLUSIONS: There were no abnormal findings on
      transcranial electric motor-evoked potential monitoring even in those patients
      who developed postoperative C5 palsy. These results indicate that the development
      of postoperative segmental motor paralysis after cervical laminoplasty occurs
      even if there are no abnormal findings during intraoperative monitoring.

PMID- 22454185
TI  - Polymethylmethacrylate augmentation of pedicle screws increases the initial
      fixation in osteoporotic spine patients.
AB  - STUDY DESIGN: A retrospective comparative study. OBJECTIVES: To investigate the
      clinical efficacy of polymethylmethacrylate (PMMA) augmentation in vertebral
      pseudarthrosis after osteoporotic vertebral fractures. SUMMARY OF BACKGROUND
      DATA: Despite being the most rigid form of posterior instrumentation, pedicle
      screws sometimes achieve poor initial fixation primarily in patients with
      osteoporosis. One method for improving pedicle screw fixation in osteoporotic
      spines is pedicle augmentation using bone cement such as PMMA. Although various
      biomechanical studies of osteoporotic spines have shown improved pullout strength
      of pedicle screws augmented with bone cement, there have been few studies that
      have examined the clinical significance of PMMA augmentation. METHODS: Thirty
      eight patients with posterior fusion using pedicle screws for vertebral
      pseudarthrosis after osteoporotic vertebral fracture were included in the study.
      The level of fracture ranged from T7 to L5. The mean follow-up period was 31
      months. Patients were divided into 2 groups: those with posterior instrumentation
      using pedicle screws augmented with PMMA (group C, N=17) and those without PMMA
      augmentation (group NC, N=21). Clinical and radiographic results for the 2 groups
      were compared. RESULTS: With the exception of osteoporotic status, there were no
      significant differences in the baseline data of the 2 groups. The incidence of
      clear zones around the pedicle screws was significantly suppressed in group C
      compared with group NC (29.4% vs. 71.4%). Correction loss was significantly
      decreased (3 degrees vs. 7.2 degrees) and fusion rate was significantly higher in
      group C (94.1% vs. 76.1%). Back pain improved in 64.7% of the group C patients.
      There were no perioperative complications related to the PMMA cement in group C.
      CONCLUSIONS: Reinforcement of pedicle screws using PMMA augmentation may be a
      feasible surgical technique for osteoporotic spines.

PMID- 22454186
TI  - Risk of developing disability in pre and post-multidrug therapy treatment among
      multibacillary leprosy: Agra MB Cohort study.
AB  - OBJECTIVES: If leprosy is a public health problem, it is due to the disabilities
      it causes. Surprisingly little is known about the risk of disabilities. Even now,
      mainly cross-sectional studies report disability prevalence. The present study
      aims to report the risk of disability in pre and post-WHO multidrug therapy (MDT)
      in multibacillary leprosy patients and to assess the extent of the incidence of
      disability. METHODS: The study design is prospective and the setting is an
      institutional field area. Patients were detected during 2001-6 field surveys. Of
      the 289 multibacillary patients, 146 completed the study. Both sexes were
      involved. The primary outcome planned was to study cure of disease, relapses and
      disability in patients receiving MDT. The secondary outcome was to measure
      reaction and default. Assessment was done clinically. Data have been analysed
      using SPSS software, logistic, survival analysis was performed and the chi(2)
      test of significance was used. RESULTS: An important risk factor was found to be
      three or more nerves involved with odds of 3.73 (1.24-11.2), and delay in
      treatment; 2.27 (1.04-4.96) at the pre-MDT stage and three or more nerves
      involved with odds of 2.81 (1.0-7.9) at the post-MDT stage. The incidence of
      disability was found to be 2.74/100 person-years; 2.69 in the MDT arm and 2.84 in
      defaulters, with slightly higher disability among early defaulters (3.08) than
      among late defaulters (2.30). The study suggests that the incidence of disability
      could be slightly higher if treatment is not completed. CONCLUSION: Early
      treatment for leprosy is a must for reducing the risk of disability, and
      treatment delay would increase the risk of disability. It is important to note
      that the incidence of disability between defaulters and those completing
      treatment was not found to be significantly different.

PMID- 22454187
TI  - Suicides by persons reported as missing prior to death: a retrospective cohort
      study.
AB  - OBJECTIVE: A first study to compare suicides by missing persons with other
      suicide cases. DESIGN: Retrospective cohort study for the period 1994-2007.  
      GEOGRAPHICAL LOCATION:  Queensland, Australia. POPULATION: 194 suicides by
      missing persons and 7545 other suicides were identified through the Queensland
      Suicide Register and the National Coroners Information System. MAIN OUTCOME
      MEASURE: chi(2) statistics and binary logistic regression were used to identify
      distinct characteristics of suicides by missing persons. RESULTS: Compared with
      other suicide cases, missing persons significantly more often died by motor
      vehicle exhaust gas toxicity (23.7% vs 16.4%; chi(2)=7.32, p<0.01), jumping from
      height (6.7% vs 3.2%; chi(2)=7.08, p<0.01) or drowning (8.2% vs 1.8%;
      chi(2)=39.53, p<0.01), but less frequently by hanging (29.4% vs 39.9%;
      chi(2)=8.82, p<0.01). They were most frequently located in natural outdoors
      locations (58.2% vs 11.1%; chi(2)=388.25, p<0.01). Persons gone missing were less
      likely to have lived alone at time of death (OR 0.45, 95% CI 0.26 to 0.76), yet
      more likely to be institutionalised (OR 3.12, 95% CI 1.28 to 7.64). They were
      less likely to have been physically ill (OR 0.64, 95% CI 0.43 to 0.95) or have a
      history of problematic consumptions of alcohol (OR 0.52, 95% CI 0.31 to 0.87). In
      comparison to other suicide cases, missing persons more often communicated their
      suicidal intent prior to death (OR 1.58, 95% CI 1.13 to 2.22). CONCLUSIONS:
      Suicides by missing persons show several distinct characteristics in comparisons
      to other suicides. The findings have implications for development of suicide
      prevention strategies focusing on early identification and interventions
      targeting this group. In particular, it may offer assistance to police in
      designing risk assessment procedures and subsequent investigations of missing
      persons.

PMID- 22454188
TI  - Why do so few patients with heart failure participate in cardiac rehabilitation?
      A cross-sectional survey from England, Wales and Northern Ireland.
AB  - OBJECTIVES: To determine why so few patients with chronic heart failure in
      England, Wales and Northern Ireland take part in cardiac rehabilitation. DESIGN:
      Two-stage, postal questionnaire-based national survey. PARTICIPANTS AND SETTING:
      Stage 1: 277 cardiac rehabilitation centres that provided phase 3 cardiac
      rehabilitation in England, Wales and Northern Ireland registered on the National
      Audit of Cardiac Rehabilitation register. Stage 2: 35 centres that indicated in
      stage 1 that they provide a separate cardiac rehabilitation programme for
      patients with heart failure. RESULTS: Full data were available for 224/277 (81%)
      cardiac rehabilitation centres. Only 90/224 (40%) routinely offered phase 3
      cardiac rehabilitation to patients with heart failure. Of these 90 centres that
      offered rehabilitation, 43% did so only when heart failure was secondary to
      myocardial infarction or revascularisation. Less than half (39%) had a specific
      rehabilitation programme for heart failure. Of those 134 centres not providing
      for patients with heart failure, 84% considered a lack of resources and 55%
      exclusion from commissioning contracts as the reason for not recruiting patients
      with heart failure. Overall, only 35/224 (16%) centres provided a separate
      rehabilitation programme for people with heart failure. CONCLUSIONS: Patients
      with heart failure as a primary diagnosis are excluded from most cardiac
      rehabilitation programmes in England, Wales and Northern Ireland. A lack of
      resources and direct exclusion from local commissioning agreements are the main
      barriers for not offering rehabilitation to patients with heart failure.

PMID- 22454189
TI  - Protocol for the Northern Manhattan Diabetes Community Outreach Project. A
      randomised trial of a community health worker intervention to improve diabetes
      care in Hispanic adults.
AB  - OBJECTIVE: Hispanics in the USA are affected by the diabetes epidemic
      disproportionately, and they consistently have lower access to care, poorer
      control of the disease and higher risk of complications. This study evaluates
      whether a community health worker (CHW) intervention may improve clinically
      relevant markers of diabetes care in adult underserved Hispanics. METHODS AND
      ANALYSIS: The Northern Manhattan Diabetes Community Outreach Project (NOCHOP) is
      a two-armed randomised controlled trial to be performed as a community-based
      participatory research study performed in a Primary Care Setting in Northern
      Manhattan (New York City). 360 Hispanic adults with poorly controlled type 2
      diabetes mellitus (haemoglobin A1c >8%), aged 35-70 years, will be randomised at
      a 1:1 ratio, within Primary Care Provider clusters. The two study arms are (1) a
      12-month CHW intervention and (2) enhanced usual care (educational materials
      mailed at 4-month intervals, preceded by phone calls). The end points, assessed
      after 12 months, are primary = haemoglobin A1c and secondary = blood pressure and
      low-density lipoprotein-cholesterol levels. In addition, the study will describe
      the CHW intervention in terms of components and intensity and will assess its
      effects on (1) medication adherence, (2) medication intensification, (3) diet and
      (4) physical activity. ETHICS AND DISSEMINATION: All participants will provide
      informed consent; the study protocol has been approved by the Institutional
      Review Board of Columbia University Medical Center. CHW interventions hold great
      promise in improving the well-being of minority populations who suffer from
      diabetes mellitus. The NOCHOP study will provide valuable information about the
      efficacy of those interventions vis-a-vis clinically relevant end points and will
      inform policy makers through a detailed characterisation of the programme and its
      effects. CLINICAL TRIAL REGISTRATION NUMBER: NCT00787475 at clinicaltrials.gov.

PMID- 22454190
TI  - Plasticity of melanoma cells induced by neural cell crest conditions and three
      dimensional growth.
AB  - Melanoma tumors have been shown to comprise both invasive and proliferative cell
      subpopulations. These populations are highly plastic, thus hampering full
      characterization and therapeutic targeting of dormant and partially
      dedifferentiated invasive cells. We have reported, previously, that melanoma
      cells grown in a serum-free neural crest medium, in which they propagate as
      spheroids, show higher invasiveness and increased immune escape. In addition, in
      spheroids, we showed the increased expression of several genes which are involved
      in pluripotency, differentiation, and invasion. We therefore proposed that these
      culture conditions favor the polarization of proliferative melanoma cells toward
      an invasive state. As plasticity may suggest a reversible polarization, the aim
      of this report is to assess the transient phenotype of invasive cells generated
      through this procedure. We provide evidence that spheroid cells mimic dormant
      populations, and that this phenotype is fully reversible when cells are
      reintroduced into culture media that contain serum in which they grow as a
      monolayer. We also show that most transcriptional deregulations can be reversed.
      To further explain this plasticity in melanoma cells, we explored the epigenetic
      status of four gene promoters, assuming changes in acetylation or dimethylation
      on histone 3. We show reversible modifications on lysine 9 and lysine 4. We
      propose that spheroids allow the transient polarization of melanoma cells toward
      enhanced dormancy, loss of differentiation, and invasiveness, thereby reproducing
      the properties and plasticity of invasive subpopulations in melanoma tumors. This
      in-vitro model will allow further characterization and targeting of melanoma
      invasive cell populations.

PMID- 22454192
TI  - Accumulation of mature B cells in the inflamed muscle tissue of a patient with
      anti-155/140 antibody-positive juvenile dermatomyositis.
AB  - We report the first case of a Japanese patient with anti-155/140 antibody
      positive juvenile dermatomyositis (JDM). Her clinical features included severe
      cutaneous involvement. Serum B cell-activating factor levels were significantly
      increased. Mature class-switched memory B cells accumulated in inflamed muscle
      tissue but decreased in peripheral blood. These findings indicate that loss of B
      cell tolerance and accumulation of mature B cells in inflamed muscle tissue play
      an important role in the pathogenesis of JDM.

PMID- 22454191
TI  - Serum antibodies against the 70k polypeptides of the U1 ribonucleoprotein complex
      are associated with psychiatric syndromes in systemic lupus erythematosus: a
      retrospective study.
AB  - OBJECTIVES: We assessed the association between serum autoantibodies against the
      70-kDa polypeptide of the U1-ribonucleoprotein (RNP) complex (U1-70k) and the
      central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE)
      patients. METHODS: We studied 106 hospitalized patients with active SLE,
      comparing those with (n = 32) and without (n = 74) CNS syndromes. CNS syndromes
      were further classified into neurologic (n = 21) and psychiatric (n = 15)
      disorders. Immunoglobulin G (IgG) anti-U1-70k antibodies were measured by enzyme
      linked immunosorbent assay (ELISA) using recombinant antigens. IgG antibodies
      against whole U1-RNP were measured using commercial ELISA kits. RESULTS: Although
      there was no significant difference in the levels of serum anti-U1-70k antibodies
      in SLE patients with or without CNS syndromes (p = 0.83), the levels were
      significantly elevated in SLE patients compared with patients without psychiatric
      syndromes (p = 0.030). In contrast, no significant difference was observed in the
      levels of serum anti-U1-RNP antibodies in SLE patients with or without
      psychiatric syndromes (p = 0.555). CONCLUSIONS: These results indicate that serum
      anti-U1-70k antibodies are associated with psychiatric syndromes in SLE but that
      they are not associated with CNS syndromes as a whole or with neurologic
      syndromes. The anti-U1-70k antibodies might be involved in the pathological
      mechanisms of psychiatric syndromes in SLE.

PMID- 22454194
TI  - Dental implants stimulate expression of Interleukin-8 and its receptor in human
      blood--an in vitro approach.
AB  - Interleukin (IL)-8 secreted from osteoblasts and peripheral blood monocytes
      increases in patients with aseptic hip-implant loss and in patients with
      mucositis after dental implant insertion. We explored in vitro the possibility of
      an IL-8-mediated inflammatory response as a consequence of contact between
      different dental implant surfaces and human blood. Titanium and zirconia implants
      were incubated in human blood. Nonstimulated blood served as negative, while
      blood stimulated with bacterial lipopolysaccharides (LPS) served as positive
      control. After depyrogenization, to examine the possible role of LPS, implants
      were again submerged in blood. Gene-expression of IL-8 and its receptor was
      measured by real-time quantitative polymerase chain reaction. In a receptor
      mediated, but LPS-independent manner, titanium implants led to a more pronounced
      increase in IL-8 gene expression when compared with zirconia implants.
      Depyrogenization resulted after 24 h in zirconia implants in decreased IL-8 gene
      expression. Altered IL-8 expression could indicate aseptic, at least LPS
      independent implant loss, which may be an additional feature in the manifestation
      of peri-implantitis, possibly triggered by microscopically small implant
      particles. Hence, opening a new field of investigations to further understand the
      possible mechanism underlying the manifestation of implant failure.

PMID- 22454193
TI  - Protective effects of ginsenoside Rg3 on human osteoarthritic chondrocytes.
AB  - OBJECTIVES: To explore whether Rg3, a major and especially potent ginsenoside,
      modulates human osteoarthritic (OA) chondrocyte senescence. METHODS: Isolated
      chondrocytes were cultured in medium containing interleukin-1 beta (IL-1beta)
      with or without Rg3. The expression levels of mRNAs encoding aggrecan (ACAN), a
      major structural proteoglycan, type II collagen (COL2A1), and metalloproteinases
      (MMP) -1, -3, and -13, respectively, were determined using real-time PCR.
      Cellular senescence was detected by measuring senescence-associated beta
      galactosidase (SA-beta-Gal) activity. Chondrocyte telomerase activity also served
      as a senescence marker. RESULTS: Chondrocytes stimulated by IL-1beta showed
      increased MMP-1, MMP-3, and MMP-13 levels, whereas the expression of COL2A1 and
      ACAN decreased. However, in cells co-treated with IL-1beta and Rg3, the levels of
      MMP-1 and MMP-13 were lower than in cells treated with IL-1beta alone, and COL2A1
      and ACAN expression levels recovered from the low values seen when cultured only
      in the presence of IL-1beta. Also, compared to vehicle-treated controls, IL-1beta
      stimulation alone resulted in an increased number of SA-beta-Gal-positive cells,
      while co-incubation with IL-1beta and Rg3 significantly suppressed the expression
      of this senescence marker. Chondrocytes cultured with Rg3 showed significantly
      higher proliferative and telomerase activities than did control cells.
      CONCLUSIONS: These findings indicate that Rg3 protects the cell against the
      development of chondrocyte senescence in osteoarthritis.

PMID- 22454197
TI  - [New developments in diagnostics and treatment of cardiovascular diseases].

PMID- 22454196
TI  - Efficient replication of primary or culture hepatitis C virus isolates in human
      liver slices: a relevant ex vivo model of liver infection.
AB  - The development of human cultured hepatitis C virus (HCV) replication-permissive
      hepatocarcinoma cell lines has provided important new virological tools to study
      the mechanisms of HCV infection; however, this experimental model remains
      distantly related to physiological and pathological conditions. Here, we report
      the development of a new ex vivo model using human adult liver slices culture,
      demonstrating, for the first time, the ability of primary isolates to undergo de
      novo viral replication with the production of high-titer infectious virus as well
      as Japanese fulminant hepatitis type 1, H77/C3, and Con1/C3. This experimental
      model was employed to demonstrate HCV neutralization or HCV inhibition, in a dose
      dependent manner, either by cluster of differentiation 81 or envelope protein 2
      specific antibodies or convalescent serum from a recovered HCV patient or by
      antiviral drugs. CONCLUSION: This new ex vivo model represents a powerful tool
      for studying the viral life cycle and dynamics of virus spread in native tissue
      and also allows one to evaluate the efficacy of new antiviral drugs.

PMID- 22454195
TI  - Molecular and cellular mechanisms involved in the Trypanosoma cruzi/host cell
      interplay.
AB  - The protozoan parasite Trypanosoma cruzi has a complex biological cycle that
      involves vertebrate and invertebrate hosts. In mammals, the infective
      trypomastigote form of this parasite can invade several cell types by exploiting
      phagocytic-like or nonphagocytic mechanisms depending on the class of cell
      involved. Morphological studies showed that when trypomastigotes contact
      macrophages, they induce the formation of plasma membrane protrusions that differ
      from the canonical phagocytosis that occurs in the case of noninfective
      epimastigotes. In contrast, when trypomastigotes infect epithelial or muscle
      cells, the cell surface is minimally modified, suggesting the induction of a
      different class of process. Lysosomal-dependent or -independent T. cruzi invasion
      of host cells are two different models that describe the molecular and cellular
      events activated during parasite entry into nonphagocytic cells. In this context,
      we have previously shown that induction of autophagy in host cells before
      infection favors T. cruzi invasion. Furthermore, we demonstrate that
      autophagosomes and the autophagosomal protein LC3 are recruited to the T. cruzi
      entry sites and that the newly formed T. cruzi parasitophorous vacuole has
      characteristics of an autophagolysosome. This review summarizes the current
      knowledge of the molecular and cellular mechanisms of T. cruzi invasion in
      nonphagocytic cells. Based on our findings, we propose a new model in which T.
      cruzi takes advantage of the upregulation of autophagy during starvation to
      increase its successful colonization of host cells.

PMID- 22454198
TI  - [Prognostic impact of heart failure with preserved versus reduced ejection 
      fraction in patients with mild symptoms].
AB  - BACKGROUND AND AIM: Previous studies have found a similarly impaired prognosis in
      patients with heart failure with preserved ejection fraction (HFpEF) as in
      patients with systolic heart failure (HFrEF). This study examines the prognosis
      of HFpEF patients with only mild symptoms and compares two different methods of
      diagnosing HFpEF. METHODS: Of 670 consecutive patients presenting in our
      outpatient clinic (57.6 +/- 16 years, 50.1 % male), 165 revealed a typical
      clinical presentation with heart failure NYHA class II-III. The following
      echocardiographic parameters were assessed: ejection fraction (EF), left atrial
      size (LA), early and late antegrade mitral flow (E and A), early mitral annular
      movement (E'). Criteria for HFrEF were typical symptoms (NYHA II-III) and an EF <
      50 %, HFpEF was diagnosed in patients with typical presentation, NYHA >= 2 and EF
      >= 50 % using 2 different definitions: similarly to the criteria of the I
      Preserve study or as recommended by the german association of cardiology (DGK)
      that imply prove of diastolic dysfunction. Patients were followed-up for up to
      2.5 years (mean 1.7+/-0.7) and the following events were registered: death,
      hospitalisation (myocardial infarction/coronary intervention/cardiac
      decompensation), cardiac transplantation (HTX). RESULTS: The majority (93.3 %) of
      the 165 heart failure patients had mild symptoms NYHA II. Of the 165 patients
      with typical symptoms, systolic heart failure could be found in 51 (30.9 %) and
      HFpEF according to I-Preserve criteria in 114 (69.1 %) patients. 56 (33.9 %)
      patients fulfilled the DGK criteria for HFpEF. Patients with HFpEF were
      significantly older, more often obese, female and hypertensive. The event rate
      was higher in patients with systolic heart failure (32 events, 62.7 %) than in
      patients with HFpEF (I-PRESERVE criteria: 28 events, 24.6 %; DGK criteria: 16
      events, 28.6 %; both p < 0,001, log-rank), whereby this difference was mainly
      caused by increased hospitalisations (43.1 vs. 14.9 and 21,4 %, p < 0.001 and p <
      0.016). Significantly more patients with HFrEF reached the combined end point
      death/HTX (p = 0.019 [I-Preserve] and p = 0.022 [DGK]). Both HFpEF groups showed
      no significant difference in any of the event types. CONCLUSION: Patients with
      HFpEF and mild symptoms have a more benign prognosis than those with systolic
      heart failure. Whether additional echocardiographic measurements are valuable for
      the diagnosis of HFpEF has to be proved in larger studies.

PMID- 22454199
TI  - [35-year-old woman with unclear cardiac surgery in infancy. Operation of atrial
      septal defect type 1 (ostium primum defect) with mitral valve involvement].

PMID- 22454200
TI  - [Myocardial infarction (NSTEMI) in a young patient with coronary aneurysm].
AB  - HISTORY AND ADMISSION FINDINGS: A 28-year-old man without a significant past
      medical history presented to our emergency department with severe chest pain and
      dyspnoa. Vital signs and the rest of the physical examination were unremarkable.
      INVESTIGATIONS: The electrocardiogram showed T-wave inversions and the cardiac
      enzymes were elevated. TREATMENT AND COURSE: Angiocardiography showed an aneurysm
      of the right coronary artery and a thrombus formation in its distal part.
      Intracoronary thrombolytic therapy was attempted an oral anticoagulation was
      started. Further investigations did not find the cause of the aneurysmatic RCA.
      The patient had no further episode of chest pain. CONCLUSION: Acute coronary
      syndrome is a rare finding in patients under the age of 30 years. Coronary
      aneurysms with associated thrombus can be the cause of it.

PMID- 22454201
TI  - [Renal denervation in hypertension - pro].

PMID- 22454202
TI  - [Renal denervation in hypertension - contra].

PMID- 22454203
TI  - [Modern treatment in acute coronary syndrome].
AB  - The "acute coronary syndrome" (ACS) is a life threatening condition. In patients
      with ST-segment elevation myocardial infarction (STEMI) an immediate reperfusion
      therapy is indicated. Primary percutaneous coronary intervention (PCI) is the
      gold standard. In ACS without ST-segment elevation (NSTE-ACS) coronary
      angiography should be performed within 72 hours in patients with risk factors.
      Depending on the coronary anatomy treatment options are PCI, aorto-coronary
      bypass surgery or sole medical therapy. The antiplatelet therapy has a key role
      in ACS. In addition to acetylsalicylic acid (ASA) another platelet aggregation
      inhibitor should be given for 12 months. For the majority of patients ticagrelor
      and prasugrel are the agents of first choice, because both act faster and
      stronger than clopidogrel. In patients at high risk of bleeding clopidogrel
      remains the preferable antiplatelet agent. In addition to antiplatelet treatment
      anticoagulant therapy is necessary in ACS-patients.

PMID- 22454204
TI  - [Intravascular imaging and its integration into coronary angiography].
AB  - Despite technical innovations of non-invasive coronary imaging modalities,
      coronary angiography still remains the standard of reference for the assessment
      of CAD.The advances in interventional cardiology require also increased imaging
      capabilities, which cannot be fully addressed by conventional coronary
      angiography. Intravascular ultrasound (IVUS) and optical coherence tomography
      (OCT) as well as near infrared spectroscopy (NIRS) are important developments and
      will be covered in this review article.IVUS was already around in interventional
      cardiology since the 90ies. It was the first to offer a high resolution
      tomographic image of the coronary arteries in vivo. Beyond that, it is also
      frequently used for peri- and postprocedural imaging. Furthermore, the
      radiofrequency information ("virtual histology") can be applied to perform a
      basic tissue characterization.Using near coherent light instead of ultrasound,
      optical coherence tomography (OCT) is able to deliver a 10 fold higher resolution
      compared to IVUS when imaging coronary plaques.This allows also for the detection
      of potential vulnerable lesions as well as for the detection of neo-intimal stent
      strut coverage following stent placement.Using near infrared spectroscopy (NIRS)
      even insights into the chemical composition of coronary plaques can be
      achieved.The development of advanced image acquisition technologies enables us to
      combine modern intravascular imaging technologies and conventional coronary
      angiography and hereby achieve additional benefit.

PMID- 22454205
TI  - [Regenerative treatment of advanced heart disease].

PMID- 22454206
TI  - [Treatment of atrial fibrillation - status quo].

PMID- 22454207
TI  - Abstracts of the Research Symposium Rheumatology and Dermatology. September 16
      17, 2011. Berlin, Germany.

PMID- 22454208
TI  - Engineered bacteriorhodopsin: a molecular scale potential switch.
AB  - Bacteriorhodopsin, BR, is a natural, photoresponsive, biomolecule that has
      potential application in data storage, imaging and sensing. Being membrane-bound,
      however, it is coupled with metallic electronic surfaces only with some
      difficulty. We report herein a facile method to generate uniformly orientated,
      anchored and active monolayers of BR on metallic electrodes. In the present
      study, the cytoplasmic side of the BR is equipped with an engineered cysteine to
      achieve largely lipid-free, orientation-specific, highly stable, covalent
      immobilization on gold surfaces. By using non-invasive Kelvin probe force
      microscopy, it is possible to measure the light-induced proton accumulation at
      the extracellular protein surface at truly molecular scales. The intimate probe
      BR interaction possible on lipid removal facilitates the detection of
      photoinduced surface potential switching substantially larger ((20.4 +/- 7.5) mV)
      with functional single delipidated mutant BR trimers than for the wild-type
      protein. The proton pumping detected is also notably highly unidirectional with
      the orientated protein.

PMID- 22454209
TI  - Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.
AB  - Interpretation of the new wealth of gene expression and molecular mechanisms in
      the developing mouse spinal cord requires an accurate anatomical base on which
      data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4
      mouse to facilitate direct comparison with the adult specimens and to contribute
      to studies of the development of the mouse spinal cord. This study presents the
      anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl
      cholinesterase-stained sections. It includes a detailed map of the laminar
      organization of selected spinal cord segments and a description of named cell
      groups of the spinal cord such as the central cervical (CeCv), lateral spinal
      nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also
      been identified according to the muscle groups they are likely to supply. General
      features of Rexed's laminae of the P4 spinal cord showed similarities to that of
      the adult (P56). However, certain differences were observed with regard to the
      extent of laminae and location of certain cell groups, such as the dorsal nucleus
      having a more dispersed structure and a more ventral and medial position or the
      CeCv being located in the medial part of lamina 5 in contrast to the adult where
      it is located in lamina 7. Motor neuron pools appeared to be more tightly packed
      in the P4 spinal cord. The dorsal horn was relatively larger and there was more
      white matter in the P56 spinal cord.

PMID- 22454210
TI  - Expression of BAG-1 and PARP-1 in precursor lesions and invasive cervical cancer
      associated with human papillomavirus (HPV).
AB  - Cervical cancer remains persistently the second most common malignancies among
      women worldwide, responsible for 500,000 new cases annually. Only in Brazil, the
      estimate is for 18,430 new cases in 2011. Several types of molecular markers have
      been studied in carcinogenesis including proteins associated with apoptosis such
      as BAG-1 and PARP-1. This study aims to demonstrate the expression of BAG-1 and
      PARP-1 in patients with low-grade squamous intraepithelial lesions (LSILs), high
      grade squamous intraepithelial lesions (HSILs) and invasive squamous cell
      carcinomas (SCCs) of the uterine cervix and to verify a possible association with
      HPV infection. Fifty samples of LSILs, 50 samples of HSILs and 50 samples of
      invasive SCCs of the uterine cervix were analyzed by immunohistochemistry for BAG
      1 and PARP-1 expression. PCR was performed to detect and type HPV DNA. BAG-1
      expression levels were significantly different between LSILs and HSILs (p =
      0,014) and between LSILs and SCCs (p = 0,014). In regards to PARP-1 expression,
      we found significant differences between the expression levels in HSILs and SCCs
      (p = 0,022). No association was found between BAG-1 expression and the presence
      of HPV. However, a significant association was found between PARP-1 expression
      and HPV positivity in the HSILs group (p = 0,021). In conclusion our research
      suggests that BAG-1 expression could contribute to the differentiation between
      LSIL and HSIL/SCC whereas PARP-1 could be useful to the differentiation between
      HSIL HPV-related and SCC. Further studies are needed to clarify the molecular
      aspects of the relationship between PARP-1 expression and HPV infection, with
      potential applications for cervical cancer prediction.

PMID- 22454211
TI  - Quick and effective hyperpolarization of the membrane potential in intact smooth
      muscle cells of blood vessels by synchronization modulation electric field.
AB  - Blood vessel dilation starts from activation of the Na/K pumps and inward
      rectifier K channels in the vessel smooth muscle cells, which hyperpolarizes the
      cell membrane potential and closes the Ca channels. As a result, the
      intracellular Ca concentration reduces, and the smooth muscle cells relax and the
      blood vessel dilates. Activation of the Na/K pumps and the membrane potential
      hyperpolarization plays a critical role in blood vessel functions. Previously, we
      developed a new technique, synchronization modulation, to control the pump
      functions by electrically entraining the pump molecules. We have applied the
      synchronization modulation electric field noninvasively to various intact cells
      and demonstrated the field-induced membrane potential hyperpolarization. We
      further applied the electric field to blood vessels and investigated the field
      induced functional changes of the vessels. In this paper, we report the results
      in a study of the membrane potential change in the smooth muscle cells of
      mesenteric blood vessels in response to the oscillating electric field. We found
      that the synchronization modulation electric field can effectively hyperpolarize
      the muscle membrane potential quickly in seconds under physiological conditions.

PMID- 22454212
TI  - Hair strands within a congenital H-type tracheoesophageal fistula.

PMID- 22454213
TI  - Further electrophysiological studies on cellular effect of herbicide, bromoxynil,
      using characean cells.
AB  - In the previous paper, I reported that 3,5-dibromo-4-hydroxybenzonitrile
      (bromoxynil) depolarizes the plasma membrane by inhibiting the electrogenic
      proton pump and discussed that the inhibition is caused by cytosol acidification
      due to influx of protonated bromoxynil and following release of proton (Shimmen
      in J Plant Res 123:715-722, 2010). However, a possibility of direct inhibition of
      the proton pump by bromoxynil flowed into the cell could not be excluded. In the
      present study, the direct effect of bromoxynil on the proton pump was
      unequivocally excluded.

PMID- 22454214
TI  - Percutaneous intracardiac baffle stenting after a scimitar vein correction.
AB  - A typical scimitar vein was surgically corrected in a female patient of 35 years
      old. The postoperative course was uneventful and in the first months after the
      functional capacity normalized. Six months after the correction, the patient
      developed progressive dyspnea. Kinking and distal stenosis of the intracardiac
      baffle which connected the scimitar vein to the left atrium were diagnosed.
      Balloon dilatation and stenting could normalize the blood flow through the
      baffle. The patient remains symptom-less up to six months after the procedure.

PMID- 22454215
TI  - Simultaneous presentation of tubal and primary abdominal pregnancies following
      clomiphene citrate treatment.
AB  - Abdominal pregnancy is a rare condition that is potentially life-threatening for
      the mother. We present a case of simultaneous ectopic pregnancies (EPs) in the
      right fallopian tube and in the vesicouterine pouch. A 26-year-old woman had
      undergone prior ovulation induction with clomiphene citrate and human chorionic
      gonadotropin (hCG) at an outside hospital for unexplained infertility. The
      patient was referred to our hospital for a suspected ectopic pregnancy at 6 weeks
      gestation. Transvaginal ultrasonography detected a viable fetus at the anterior
      left side of the uterus; therefore, we suspected a left tubal pregnancy. However,
      laparoscopic surgery revealed that EPs were located in both the left
      vesicouterine pouch and in the right fallopian tube. Resection of the right
      salpinx and abdominal implant were performed. Histopathological examination
      confirmed the simultaneous presentation of a primary abdominal pregnancy and a
      right tubal pregnancy. After surgery, the patient's serum hCG level returned to
      normal. Concurrent EPs and abdominal pregnancy are very rare. However, it should
      be noted that reproductive technologies sometimes cause unusual clinical
      situations. A thorough abdominal inspection is needed.

PMID- 22454216
TI  - The etiology of maternal mortality in developed countries: a systematic review of
      literature.
AB  - PURPOSE: To review the literature about MD in developed countries. METHODS: A
      search in PubMed, EMBASE, Medline and reference lists was performed. Key words:
      maternal death/mortality, pregnancy death and obstetric/maternity care. Articles
      were selected if they reported the cause of death per livebirths, were performed
      in developed countries and unselected population, classified MD by the World
      Health Organization. Maternal age, cause of MD, time of MD (antepartum,
      intrapartum, postpartum) and delivery mode were abstracted. MD was expressed as
      maternal mortality ratio (MMR). PRISMA guidelines were followed. RESULTS: Twelve
      articles provided data from 1980 to 2007. The MD rate was 9,750 in 75,560,683
      livebirths (MMR: 12.90). MD was direct in 6,791 women (MMR: 8.98), being
      postpartum hemorrhage the leading cause, and indirect in 2,786 women (MMR: 3.68),
      with cardiovascular disease as the main cause. The remaining 173 deaths (MMR:
      0.22) were unexplained. Maternal age >45 years, vaginal delivery, postpartum
      period increased the risk of MD. MD reduced over time in all countries except in
      the Netherlands and USA. CONCLUSIONS: Conditions leading to hemorrhage warrant
      strict management. The risk of an apparently healthy woman to die during
      motherhood is 0.22 out of 100,000 livebirths.

PMID- 22454217
TI  - Gold nanoparticles supported on nanoparticulate ceria as a powerful agent against
      intracellular oxidative stress.
AB  - Ceria-supported gold nanoparticles are prepared exhibiting peroxidase activity
      and acting as radical traps. Au/CeO(2)  shows a remarkable biocompatibility as
      demonstrated by measuring cellular viability, proliferation, and lack of
      apoptosis for two human cell lines (Hep3B and HeLa). The antioxidant activity of
      Au/CeO(2)  against reactive oxygen species (ROS) is demonstrated by studying the
      cellular behavior of Hep3B and HeLa in a model of cellular oxidative stress. It
      is determined that Au/CeO(2)  exhibits higher antioxidant activity than
      glutathione, the main cytosolic antioxidant compound, and its CeO(2)  carrier.
      Overall the result presented here shows the potential of implementing well
      established nanoparticulated gold catalysts with remarkable biocompatibility in
      cellular biology.

PMID- 22454218
TI  - School nursing in New Zealand: a study of services.
AB  - There are universal concerns about youth health and recognition of the potential
      of school health services but little consensus internationally as to how these
      are best configured. Limited information about nursing services in New Zealand
      secondary schools, changing patterns of youth health needs and expanding roles
      for nurses in primary health care indicated a need to research school nursing
      services. This study found that within New Zealand schools there was wide
      variation in the types of health services and their funding; that nurses are well
      qualified and highly experienced, although some lack clinical supervision; that
      students present most commonly for sexual health and injuries or sickness; and
      that they choose school health services for accessibility and confidentiality. It
      concludes that one way forward would be to develop a national-level policy for
      nurse-led school health centers, with appropriate funding, that allows for local
      flexibility and includes a career pathway for school nurses.

PMID- 22454219
TI  - Health reform and the constitutionality of the individual mandate.
AB  - The Patient Protection and Affordable Care Act (ACA) of 2010 is landmark
      legislation designed to expand access to health care for virtually all legal U.S.
      residents. A vital but controversial provision of the ACA requires individuals to
      maintain health insurance coverage or face a tax penalty-the individual mandate.
      We examine the constitutionality of the individual mandate by analyzing relevant
      court decisions. A critical issue has been defining the "activities" Congress is
      authorized to regulate. Some judges determined that the mandate was
      constitutional because the decision to go without health insurance, that is, to
      self-insure, is an activity with substantial economic effects within the overall
      scheme of the ACA. Opponents suggest that Congress overstepped its authority by
      regulating "inactivity," that is, compelling people to purchase insurance when
      they otherwise would not. The U.S. Supreme Court is set to review the issues and
      the final ruling will shape the effectiveness of health reform.

PMID- 22454220
TI  - Persistency with zoledronic acid is associated with clinical benefit in patients
      with multiple myeloma.
AB  - Zoledronic acid (ZOL), an intravenous bisphosphonate, has been shown to reduce
      and delay the incidence of skeletal-related events (SREs) in multiple myeloma
      (MM) patients with bone disease. A retrospective claims-based analysis was
      conducted that used two distinct US managed care databases to examine the
      relationship between persistency with ZOL and clinical benefit. Patients >18
      years, diagnosed with MM, and with at least one claim for ZOL (or a claim for
      malignant bone disease and ZOL initiation within 30 days) between 1/1/2001 and
      12/31/2006 were included. Patients were evaluated for incidence of SREs and for
      mortality. Treatment persistency was defined as the absence of a >45 day gap
      between ZOL administrations. Of 1,655 patients in this analysis, 1,060 received
      ZOL and 595 received no intravenous bisphosphonate therapy. Compared with
      patients not receiving bisphosphonate therapy, ZOL-treated patients had lower
      incidences of SREs (P < 0.0001) and death (P = 0.0001). Longer persistency with
      ZOL was associated with lower risks of SREs (P = 0.001), fracture (P = 0.003),
      and death (P = 0.002) versus shorter persistency. Patients who were persistent
      with ZOL for >=1.5 years had an incidence of 15.0 SREs and 6.2 fractures per 100
      person-years. Patients who were persistent for 31-90 days had an incidence of
      24.6 SREs and 14.0 fractures per 100 person-years, and patients not receiving
      intravenous bisphosphonates had an incidence of 32.2 SREs and 16.9 fractures per
      100 person-years. These data from a real-world setting indicate that among MM
      patients, longer persistency with ZOL was associated with a lower risk of SREs
      and fracture.

PMID- 22454221
TI  - Non-adherence to immunosuppressive medications in kidney transplantation: intent
      vs. forgetfulness and clinical markers of medication intake.
AB  - BACKGROUND: Although adherence to immunosupressive medication after
      transplantation is important to maximize good clinical outcomes it remains
      suboptimal and not well-understood. The purpose of this study was to examine
      intentional and unintentional non-adherence to immunosuppression medication in
      kidney transplant patients. METHODS: A cross-sectional sample of N=218 patients
      [49.6 +/- 12.3 years] recruited in London, UK (1999-2002) completed measures of
      medication beliefs, quality-of-life, depression, and transplantation-specific
      emotions. Adherence was measured with self-report and serial immunosuppressive
      assays. RESULTS: Intentional non-adherence was low (13.8 %) yet 62.4 % admitted
      unintentional non-adherence and 25.4 % had sub-target immunosuppressive levels.
      The risk of sub-target serum immunosuppressive levels was greater for patients
      admitting unintentional non-adherence (OR=8.4; p=0.004). Dialysis vintage, doubts
      about necessity, and lower worry about viability of graft explained R(2)=16.1 to
      36 % of self-report non-adherence. Depression was related only to intentional non
      adherence. CONCLUSIONS: Non-adherence is common in kidney transplantation.
      Efforts to increase adherence should be implemented by targeting necessity
      beliefs, monitoring depression, and promoting strategies to decrease
      forgetfulness.

PMID- 22454222
TI  - Fine-needle cytology of Kaposi's sarcoma in an intramammary lymphnode: report of
      one case.
AB  - Kaposi's sarcoma (KS) is the most common human immunodeficiency virus (HIV)
      infection disease-associated malignancy. It consists of an angiosarcomatous
      change of the epithelial and mucous membrane-associated connective tissue not
      only in various sites, for example, skin, gastrointestinal system, lungs, and so
      on, but may also involve nonepithelial organs, such as lymphnodes. An unusual
      localization of KS to an intramammary lymphnode is reported here. The patient, an
      HIV-negative 69-year-old woman with a clinical history of rheumatoid arthritis
      treated with hydrocortisone, had an 8-month pathological history of biopsy-proven
      Kaposi sarcoma of the skin with visceral extension (stomach and duodenum). The
      appearance of a well-defined 23 * 20 mm(2) breast nodule during chemotherapy
      elicited fine-needle cytology to exclude breast carcinoma. Surgical excision
      confirmed the cytopathological diagnosis of Kaposis's sarcoma.

PMID- 22454223
TI  - Dual catalysis with an Ir(III)-Au(I) heterodimetallic complex: reduction of
      nitroarenes by transfer hydrogenation using primary alcohols.
AB  - A triazolyl-di-ylidene ligand has been used for the preparation of a
      homodimetallic complex of gold, and a heterodimetallic compound of gold and
      iridium. Both complexes have been fully characterized and their molecular
      structures have been determined by means of X-ray diffraction. The catalytic
      properties of these two complexes have been evaluated in the reduction of
      nitroarenes by transfer hydrogenation using primary alcohols. The two complexes
      afford different reaction products; whereas the Au(I)-Au(I) catalyst yields a
      hydroxylamine, the Ir(III)-Au(I) complex facilitates the formation of an imine.

PMID- 22454224
TI  - Antitumor and anticancer stem cell activity of a poly ADP-ribose polymerase
      inhibitor olaparib in breast cancer cells.
AB  - BACKGROUND: Although the poly adenosine diphosphate (ADP)-ribose polymerase
      (PARP) inhibitor olaparib is known to have potent antitumor activity in BRCA
      related breast cancer cells, a limited number of preclinical and clinical studies
      have shown antitumor activity of olaparib in non-BRCA-related breast cancer. We
      investigated antitumor activity of olaparib in breast cancer cell lines derived
      from patients with nonfamilial sporadic breast cancer. METHODS: Effects of
      olaparib alone or in combination with five different chemotherapeutic agents on
      cell growth, cell cycle progression, apoptosis, and proportion of cancer stem
      cells using the mammosphere assay and CD44/CD24/ESA cell surface marker assay
      were investigated in a panel of six sporadic breast cancer cell lines.
      Extracellular-signal-regulated kinase (ERK) phosphorylation was also investigated
      to elucidate action mechanisms of olaparib. RESULTS: Olaparib inhibited the
      growth of two estrogen receptor (ER)-positive and human epidermal growth factor
      receptor 2 (HER2)-negative breast cancer cell lines and two ER-negative and HER2
      negative breast cancer cell lines (50% growth inhibitory concentrations 1.3-3.0
      MUM) associated with G2/M accumulation and induction of apoptosis. In contrast,
      two HER2-positive cell lines were resistant to olaparib. Interestingly, olaparib
      significantly decreased the proportion of putative cancer stem cells in either
      sensitive or resistant cell lines. In addition, olaparib increased expression of
      p-ERK. Combined treatments of olaparib with a mitogen-activated protein kinase
      kinase (MEK) inhibitor U0126 completely suppressed expression of p-ERK. These
      treatments also inhibited the G2/M accumulation and apoptosis induction by
      olaparib. Among five chemotherapeutic agents commonly used for breast cancer
      treatment, only an irinotecan metabolite SN38 showed additive antitumor activity
      with olaparib. Importantly, the combined treatment enhanced the increase in G2/M
      accumulation and apoptosis induction as well as a decrease in the proportion of
      cancer stem cells. CONCLUSIONS: This study has indicated for the first time that
      the PARP inhibitor olaparib has substantial antitumor and anticancer stem cell
      activity in breast cancer cell lines of nonfamilial origin. Upregulation of p-ERK
      might explain, at least in part, antitumor and anticancer stem cell activity of
      olaparib. Combined treatment of olaparib with irinotecan might be effective in
      treatment of non-BRCA-related breast cancer.

PMID- 22454225
TI  - [Do gender differences exist in the outcome of rehabilitation among patients with
      chronic low back pain? Findings of a 6-months follow-up study].
AB  - This analysis assessed changes in pain intensity, subjective health status and
      psychological well-being among 237 patients (50% women) with chronic low back
      pain who were admitted to a rehabilitation clinic in Southern Bavaria. The
      findings show for both men and women a significant improvement of pain and health
      related quality of life during the 6-month follow-up period. The results indicate
      gender-specific predictors of changes, which should be taken into account at the
      start of rehabilitation.

PMID- 22454226
TI  - [The methods within the evaluation of disease management programmes in control
      group designs using the example of diabetes mellitus - a systematic literature
      review].
AB  - BACKGROUND: Disease management programmes (DMPs) were implemented in Germany in
      2002. Their evaluation is required by law. Beyond the mandatory evaluation, a
      growing number of published studies evaluate the DMP for diabetes mellitus type 2
      in a control-group design. As patients opt into the programme on a voluntary
      basis it is necessary to adjust the inherent selection bias between groups. The
      aim of this study is to review published studies which evaluate the diabetes DMP
      using a control-group design with respect to the methods used. METHODS: A
      systematic literature review of electronic databases (PUBMED, Cochrane Library,
      EMBASE, MEDPILOT) and a hand search of reference lists of the relevant
      publications was conducted to identify studies evaluating the DMP diabetes
      mellitus in a control-group design. RESULTS: 8 studies were included in the
      systematic literature review. 4 studies gathered retrospective claims data from
      sickness funds, one from physician's records, one study used prospective data
      from ambulatory care, and 2 studies were based on one patient survey. Methods
      used for adjustment of selection bias included exact matching, matching using
      propensity score methods, age-adjusted and sex-separated analysis, and adjustment
      in a regression model/analysis of covariance. One study did not apply adjustment
      methods. The intervention period ranged from 1 day to 4 years. Considered
      outcomes of studies (surrogate parameter, diabetes complications, mortality,
      quality of life, and claim data) depended on the database. CONCLUSION: In the
      evaluation of the DMP diabetes mellitus based on a control-group design neither
      the database nor the methods used for selection bias adjustment were consistent
      in the available studies. Effectiveness of DMPs cannot be judged based on this
      review due to heterogeneity of study designs. To allow for a comprehensive
      programme evaluation standardised minimum requirements for the evaluation of DMPs
      in the control group design are required.

PMID- 22454227
TI  - Self-medication among traumatized youth: structural equation modeling of pathways
      between trauma history, substance misuse, and psychological distress.
AB  - In an effort to self-medicate psychological distress stemming from exposure to
      traumatic life events, at-risk youth may be likely to seek intoxication via
      substance use. Concomitantly, self-medication with psychoactive substances is
      theorized to confer risk of developing future psychiatric and substance use
      disorders. The present study employed structural equation modeling to examine
      self-medication among a sample of 723 youth in residential treatment for
      antisocial behavior via recursive and non-recursive relationships between trauma
      history, substance misuse, and psychological distress. Results supported study
      hypotheses that: (a) the effects of trauma history on psychological distress are
      partially mediated by substance misuse, and (b) exposure to traumatic life events
      drives a feedback loop between substance misuse and psychological distress.
      Findings from this large-scale survey of adolescents exhibiting behavioral
      dysfunction suggest that identification of self-medication processes among
      traumatized youth may be crucial for developing targeted prevention and treatment
      initiatives.

PMID- 22454228
TI  - The interplay of dyadic and individual planning of pelvic-floor exercise in
      prostate-cancer patients following radical prostatectomy.
AB  - This study broadens the current understanding of the role of planning by focusing
      on the interplay between individual and dyadic planning (i.e. making plans about
      the target person's behaviour together with a partner). Self-report data from
      N=141 prostatectomy-patients and their partners were assessed at three times
      within 1 year post-surgery. Direct and indirect effects of dyadic and individual
      planning on patients' pelvic-floor exercise (PFE) were tested. Proposed mediators
      were social support, social control, and action control. Cross-sectionally, the
      dyadic planning-PFE relationship was mediated by patients' received support and
      partners' provided social control. Longitudinally, mediators of dyadic planning
      were partners' provided social control and support. Effects of individual
      planning on PFE were mediated by action control at baseline only. Also, at lower
      levels of individual planning, patients' dyadic planning was more strongly
      associated with receipt of social control. Results underscore the importance of
      social factors in the planning process and its mechanisms in health-behaviour
      change.

PMID- 22454229
TI  - Photoresponsive coumarin-stabilized polymeric nanoparticles as a detectable drug
      carrier.
AB  - The ability to create aqueous suspended stable nanoparticles of the hydrophobic
      homopolymer poly(epsilon-caprolactone) end-functionalized with coumarin moieties
      (CPCL) is demonstrated. Nanoparticles of CPCL are prepared in a continuous manner
      using nanoprecipitation. The resulting nanoparticles are spherical in morphology,
      about 40 nm in diameter, and possess a narrow size distribution and excellent
      stability over 4 months by repulsive surface charge. Nanoparticle size can be
      easily controlled by manipulating the concentration of CPCL in the solution. The
      interparticle assembly between the nanoparticles can be reversibly adjusted with
      photoirradiation due to photoinduced [2 + 2] cyclodimerization and cleavage
      between the coumarin molecules. In addition, the CPCL nanoparticles show
      significant cellular uptake without cytotoxicity, and the intrinsic fluorescence
      of the coumarin functional group permits the direct detection of cellular
      internalization.

PMID- 22454230
TI  - Vibrant Soundbridge middle ear implantations: experience at National University
      Hospital Singapore.
AB  - Vibrant Soundbridge (VSB) has been recommended for both adults and children with
      all types of hearing loss. The aim of this study was to evaluate the objective
      and subjective benefits with VSB and the difference in benefits for patients with
      different types of hearing loss. A retrospective case review was conducted on
      seven consecutive patients who had received VSB implantations at the National
      University Hospital of Singapore from March 2006 to November 2009. Patients were
      divided into the Sensorineural Hearing Loss (SNHL) Group and Conductive Hearing
      Loss (CHL)/Mixed Hearing Loss (MHL) Group. Surgical complications were evaluated,
      and objective and subjective results were compared between the two groups. No
      major complications were observed during the follow-up of up to 4 years. Greater
      objective and subjective benefits were observed in the CHL/MHL Group. Subjective
      benefits were consistent with objective improvements. Pre-operative counseling
      for realistic expectations is important, especially for patients with SNHL.

PMID- 22454231
TI  - Endoscopic treatment of anterior glottic webs according to Lichtenberger
      technique and results on 18 patients.
AB  - Anterior glottic webs are most frequently acquired and result in a major vocal
      handicap. Many treatment modalities have been reported in the literature. None of
      them achieves perfect morphological or functional results. We present our series
      treated by an endoscopic technique based on CO(2) laser section of the web,
      mitomycin application and placement of a temporary silastic stent. We
      retrospectively reviewed the charts of 18 consecutive patients with anterior webs
      treated at our university hospital between 2003 and 2010. The endoscopic
      technique consisted of the section of the web with the CO(2) Acublade system,
      immediate application of mitomycin C and placement of a silastic stent. No
      tracheostomy was required. The stent was removed 3 weeks later. Patients had a
      vocal evaluation pre and postoperatively. It consisted of a video-stroboscopic
      examination, the global score of the Voice Handicap Index, the global and
      roughness scores of the perceptive voice evaluation according to Hirano, acoustic
      and aerodynamic parameters. Eighteen patients were included in the study with a
      mean age of 46 years (min. = 5, max. = 76). Twenty-two percent were women. All
      patients had postoperative speech therapy. The mean follow-up is 48.4 months (3
      87 months). At the last follow-up, none of the patients had recurrence of the
      laryngeal web. The grade G of dysphonia significantly decreased from 2 to 1 (p =
      0.035). CO(2) laser resection of anterior webs with mitomycin C application and
      placement of a silastic stent for 3 weeks induces a good morphological result
      with absence of web reformation but without substantial voice improvement
      observed in our series.

PMID- 22454233
TI  - A quantitative atlas of polyadenylation in five mammals.
AB  - We developed PolyA-seq, a strand-specific and quantitative method for high
      throughput sequencing of 3' ends of polyadenylated transcripts, and used it to
      globally map polyadenylation (polyA) sites in 24 matched tissues in human,
      rhesus, dog, mouse, and rat. We show that PolyA-seq is as accurate as existing
      RNA sequencing (RNA-seq) approaches for digital gene expression (DGE), enabling
      simultaneous mapping of polyA sites and quantitative measurement of their usage.
      In human, we confirmed 158,533 known sites and discovered 280,857 novel sites
      (FDR < 2.5%). On average 10% of novel human sites were also detected in matched
      tissues in other species. Most novel sites represent uncharacterized alternative
      polyA events and extensions of known transcripts in human and mouse, but
      primarily delineate novel transcripts in the other three species. A total of
      69.1% of known human genes that we detected have multiple polyA sites in their
      3'UTRs, with 49.3% having three or more. We also detected polyadenylation of
      noncoding and antisense transcripts, including constitutive and tissue-specific
      primary microRNAs. The canonical polyA signal was strongly enriched and
      positionally conserved in all species. In general, usage of polyA sites is more
      similar within the same tissues across different species than within a species.
      These quantitative maps of polyA usage in evolutionarily and functionally related
      samples constitute a resource for understanding the regulatory mechanisms
      underlying alternative polyadenylation.

PMID- 22454234
TI  - RIP-chip-SRM--a new combinatorial large-scale approach identifies a set of
      translationally regulated bantam/miR-58 targets in C. elegans.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene
      expression. As miRNAs are involved in a wide range of biological processes and
      diseases, much effort has been invested in identifying their mRNA targets. Here,
      we present a novel combinatorial approach, RIP-chip-SRM (RNA-binding protein
      immunopurification + microarray + targeted protein quantification via selected
      reaction monitoring), to identify de novo high-confidence miRNA targets in the
      nematode Caenorhabditis elegans. We used differential RIP-chip analysis of miRNA
      induced silencing complexes from wild-type and miRNA mutant animals, followed by
      quantitative targeted proteomics via selected reaction monitoring to identify and
      validate mRNA targets of the C. elegans bantam homolog miR-58. Comparison of
      total mRNA and protein abundance changes in mir-58 mutant and wild-type animals
      indicated that the direct bantam/miR-58 targets identified here are mainly
      regulated at the level of protein abundance, not mRNA stability.

PMID- 22454232
TI  - A systematic study of gene expression variation at single-nucleotide resolution
      reveals widespread regulatory roles for uAUGs.
AB  - Regulatory single-nucleotide polymorphisms (rSNPs) alter gene expression. Common
      approaches for identifying rSNPs focus on sequence variants in conserved regions;
      however, it is unknown what fraction of rSNPs is undetectable using this
      approach. We present a systematic analysis of gene expression variation at the
      single-nucleotide level in the Saccharomyces cerevisiae GAL1-10 regulatory
      region. We exhaustively mutated nearly every base and measured the expression of
      each variant with a sensitive dual reporter assay. We observed an expression
      change for 7% (43/582) of the bases in this region, most of which (35/43, 81%)
      reside in conserved positions. The most dramatic changes were caused by variants
      that produced AUGs upstream of the translation start (uAUGs), and we sought to
      understand the consequences and molecular mechanisms underlying this class of
      mutations. A genome-wide analysis showed that genes with uAUGs display
      significantly lower mRNA and protein levels than genes without uAUGs. To
      determine the generality of this mechanism, we introduced uAUGs into S.
      cerevisiae genes and observed significantly reduced expression in 17/21 instances
      (p < 0.01), suggesting that uAUGs are functional in a wide variety of sequence
      contexts. Quantification of mRNA and protein levels for uAUG mutants showed that
      uAUGs affect both transcription and translation. Expression of uAUG mutants under
      the upf1Delta strain demonstrated that uAUGs stimulate the nonsense-mediated
      decay pathway. Our results suggest that uAUGs are potent and widespread
      regulators of gene expression that act by attenuating both protein and RNA
      levels.

PMID- 22454236
TI  - Evolutionary information hidden in a single protein structure.
AB  - The knowledge of conserved sequences in proteins is valuable in identifying
      functionally or structurally important residues. Generating the conservation
      profile of a sequence requires aligning families of homologous sequences and
      having knowledge of their evolutionary relationships. Here, we report that the
      conservation profile at the residue level can be quantitatively derived from a
      single protein structure with only backbone information. We found that the
      reciprocal packing density profiles of protein structures closely resemble their
      sequence conservation profiles. For a set of 554 nonhomologous enzymes, 74%
      (408/554) of the proteins have a correlation coefficient > 0.5 between these two
      profiles. Our results indicate that the three-dimensional structure, instead of
      being a mere scaffold for positioning amino acid residues, exerts such strong
      evolutionary constraints on the residues of the protein that its profile of
      sequence conservation essentially reflects that of its structural
      characteristics.

PMID- 22454235
TI  - Reconstructing ancient mitochondrial DNA links between Africa and Europe.
AB  - Mitochondrial DNA (mtDNA) lineages of macro-haplogroup L (excluding the derived
      L3 branches M and N) represent the majority of the typical sub-Saharan mtDNA
      variability. In Europe, these mtDNAs account for <1% of the total but, when
      analyzed at the level of control region, they show no signals of having evolved
      within the European continent, an observation that is compatible with a recent
      arrival from the African continent. To further evaluate this issue, we analyzed
      69 mitochondrial genomes belonging to various L sublineages from a wide range of
      European populations. Phylogeographic analyses showed that ~65% of the European L
      lineages most likely arrived in rather recent historical times, including the
      Romanization period, the Arab conquest of the Iberian Peninsula and Sicily, and
      during the period of the Atlantic slave trade. However, the remaining 35% of L
      mtDNAs form European-specific subclades, revealing that there was gene flow from
      sub-Saharan Africa toward Europe as early as 11,000 yr ago.

PMID- 22454237
TI  - Not every STEMI is atherosclerotic in nature.

PMID- 22454238
TI  - Giant cell tumor of tendon sheath: cytomorphologic and radiologic findings in 41
      patients.
AB  - Giant cell tumor of tendon sheath (GCTTS) is a common soft tissue lesion and
      presents as a firm, slow-growing, non-tender mass adjacent to the tendon sheath.
      It can be further classified into diffuse or localized types based on its growth
      pattern. Using cytomorphologic analysis, we assessed the feasibility of fine
      needle aspiration (FNA) as an initial diagnostic modality for GCTTS. Forty-one
      cases of image-guided FNA of GCTTS were retrospectively retrieved from the
      archives of The Johns Hopkins Hospital. Clinical information, imaging studies,
      histopathology, and other ancillary studies were also reviewed. The majority of
      the cytology specimens demonstrated hypercellularity. A uniform population of
      spindled to polygonal stromal cells constituted more than half of the
      cellularity. Other cell types frequently present included multinucleated giant
      cells, hemosiderin-laden macrophages, and foamy histiocytes. Nuclear grooves or
      intranuclear pseudo-inclusions present in stromal cells were also distinctive
      cytomorphologic features, but only present in less than a quarter of the cases.
      Our study has shown the usefulness and accuracy of imaging-guided FNA as a
      diagnostic tool for GCTTS. Diagnostic accuracy can be optimized with a thorough
      review of clinical history, careful physical examination, and radiologic
      correlation.

PMID- 22454240
TI  - Bifunctional rhenium complexes for the catalytic transfer-hydrogenation reactions
      of ketones and imines.
AB  - The silyloxycyclopentadienyl hydride complexes
      [Re(H)(NO)(PR(3))(C(5)H(4)OSiMe(2)tBu)] (R=iPr (3 a), Cy (3 b)) were obtained by
      the reaction of [Re(H)(Br)(NO)(PR(3))(2)] (R=iPr, Cy) with
      Li[C(5)H(4)OSiMe(2)tBu]. The ligand-metal bifunctional rhenium catalysts
      [Re(H)(NO)(PR(3))(C(5)H(4)OH)] (R=iPr (5 a), Cy (5 b)) were prepared from
      compounds 3 a and 3 b by silyl deprotection with TBAF and subsequent
      acidification of the intermediate salts [Re(H)(NO)(PR(3))(C(5)H(4)O)][NBu(4)]
      (R=iPr (4 a), Cy (4 b)) with NH(4)Br. In nonpolar solvents, compounds 5 a and 5 b
      formed an equilibrium with the isomerized trans-dihydride cyclopentadienone
      species [Re(H)(2)(NO)(PR(3))(C(5)H(4)O)] (6 a,b). Deuterium-labeling studies of
      compounds 5 a and 5 b with D(2) and D(2)O showed H/D exchange at the H(Re) and
      H(O) positions. Compounds 5 a and 5 b were active catalysts in the transfer
      hydrogenation reactions of ketones and imines with 2-propanol as both the solvent
      and H(2) source. The mechanism of the transfer hydrogenation and isomerization
      reactions was supported by DFT calculations, which suggested a secondary
      coordination-sphere mechanism for the transfer hydrogenation of ketones.

PMID- 22454239
TI  - Convergence of multiple mechanisms of steroid hormone action.
AB  - Steroid hormones modulate a wide array of physiological processes including
      development, metabolism, and reproduction in various species. It is generally
      believed that these biological effects are predominantly mediated by their
      binding to specific intracellular receptors resulting in conformational change,
      dimerization, and recruitment of coregulators for transcription-dependent genomic
      actions (classical mechanism). In addition, to their cognate ligands,
      intracellular steroid receptors can also be activated in a "ligand-independent"
      manner by other factors including neurotransmitters. Recent studies indicate that
      rapid, nonclassical steroid effects involve extranuclear steroid receptors
      located at the membrane, which interact with cytoplasmic kinase signaling
      molecules and G-proteins. The current review deals with various mechanisms that
      function together in an integrated manner to promote hormone-dependent actions on
      the central and sympathetic nervous systems.

PMID- 22454241
TI  - Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal
      and visuospatial working memory functioning.
AB  - Working memory deficits are found in different psychiatric populations and are
      most pronounced in schizophrenia. There is preliminary evidence from
      pharmacological studies that the verbal and visuospatial subcomponents of working
      memory are subject to differential neurotransmitter modulation. Here, we
      investigated the impact of well-known polymorphisms of the dopamine transporter
      gene (SLC6A3, DAT) and the catechol-O-methyl-transferase gene (COMT) as well as
      the serotonin transporter gene (SLC6A4, 5-HTT) on these specific working memory
      subcomponents in a mixed sample of patients and healthy individuals. Twenty
      healthy subjects and 80 patients diagnosed with schizophrenia, bipolar I
      disorder, or obsessive-compulsive disorder underwent genotyping for the DAT
      variable number of tandem repeats (VNTR), the COMT val/met-, and the 5-HTT
      promoter length polymorphism (5-HTTLPR) and neuropsychological testing using a
      battery of well-characterized, brain circuit-specific working memory tasks. DAT
      genotype revealed a significant and selective effect on visuospatial working
      memory, while there was no effect on verbal working memory functioning. 5-HTT
      genotype, by contrast, exerted a significant and selective effect on verbal
      working memory task performance. COMT genotype did not show any influence on
      either working memory domain. The results of the present study provide evidence
      for a differential impact of genetic polymorphisms of the dopaminergic and
      serotonergic systems on verbal and visuospatial working memory functioning.
      Together with prior evidence suggesting the existence of subgroups of
      schizophrenia patients exhibiting isolated deficits in only one working memory
      domain, this finding further supports the idea of endophenotypically and
      pathophysiologically distinct subgroups of schizophrenia with implications for
      personalized therapeutic approaches.

PMID- 22454242
TI  - D-amino acid oxidase activator gene (DAOA) variation affects cerebrospinal fluid
      homovanillic acid concentrations in healthy Caucasians.
AB  - The D-amino acid oxidase activator (DAOA) protein regulates the function of D
      amino oxidase (DAO), an enzyme that catalyzes the oxidative deamination of D-3,4
      dihydroxyphenylalanine (D-DOPA) and D-serine. D-DOPA is converted to L-3,4-DOPA,
      a precursor of dopamine, whereas D-serine participates in glutamatergic
      transmission. We hypothesized that DAOA polymorphisms are associated with
      dopamine, serotonin and noradrenaline turnover in the human brain. Four single
      nucleotide polymorphisms, previously reported to be associated with
      schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn by
      lumbar puncture, and the concentrations of the major dopamine metabolite
      homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic
      acid (5-HIAA) and the major noradrenaline metabolite 3-methoxy-4
      hydroxyphenylglycol (MHPG) were measured. Two of the investigated polymorphisms,
      rs3918342 and rs1421292, were significantly associated with CSF HVA
      concentrations. Rs3918342 was found to be nominally associated with CSF 5-HIAA
      concentrations. None of the polymorphisms were significantly associated with MHPG
      concentrations. Our results indicate that DAOA gene variation affects dopamine
      turnover in healthy individuals, suggesting that disturbed dopamine turnover is a
      possible mechanism behind the observed associations between genetic variation in
      DAOA and behavioral phenotypes in humans.

PMID- 22454244
TI  - Ultrahigh strength of dislocation-free Ni3Al nanocubes.
AB  - Individual Ni(3) Al nanocubes under pressure are investigated by comparing the
      compressive strength of both dislocation-free and irradiated Ni(3) Al nanocubes.
      The results are dicussed in light of the size-dependent and size-independent
      strength of face-centered cubic (fcc) nanocrystals in the framework of
      dislocation nucleation at free surfaces. This study sheds more light on the
      understanding of fundamental deformation mechanisms and size-affected strength in
      dislocation-free metallic nanocrystals.

PMID- 22454243
TI  - Dissociable morphometric differences of the inferior parietal lobule in
      schizophrenia.
AB  - Inferior parietal lobule (IPL) forms an integral part of a critical
      frontoparietal network, which has been implicated in various clinical symptoms
      and cognitive deficits seen in schizophrenia. Despite its functional relevance,
      the relatively few studies that have investigated the structural changes in the
      IPL report inconsistent findings concerning the nature and localization of these
      changes. We employed a blinded, automated labelling procedure to measure cortical
      thickness, surface area and the degree of cortical folding of the two distinct
      subregions of the IPL (Angular Gyrus and Supramarginal Gyrus) in 57 patients with
      schizophrenia and 41 controls using high-resolution magnetic resonance imaging.
      Within the IPL, we observed more pronounced morphological changes in
      supramarginal gyrus compared to angular gyrus in schizophrenia. While
      supramarginal gyrus in patients showed reduced gyrification, contracted surface
      area and thinning, the morphometric changes in angular gyrus were largely
      confined to a reduction in surface area. Significant hemispheric asymmetry was
      observed in the gyrification of the supramarginal gyrus. Our findings suggest
      that in addition to abnormalities in the neurodevelopmental processes that
      contribute to regional surface area and cortical thickness, a specific defect in
      cortical folding, especially affecting the left hemisphere, is likely to occur in
      schizophrenia.

PMID- 22454245
TI  - B cell immunity in allergic nasal mucosa induces T helper 2 cell differentiation.
AB  - BACKGROUND: The pathogenesis of allergic diseases is to be further understood.
      Recent studies indicate that B cells are involved in the immune regulation. The
      present study aimed to investigate the role of B cells in the initiation of
      skewed T helper (Th)2 polarization. METHODS: The surgically removed nasal mucosal
      specimens from 24 patients with allergic rhinitis (AR) and 22 patients with non
      AR (nAR) were collected. B cells isolated from the AR nasal mucosa were
      characterized. The effect of B cells on inducing naive CD4+ T cells to
      differentiate into Th2 cells was evaluated with a cell culture model. RESULTS:
      Abundant B cells were detected in the nasal mucosa of patients with AR, which
      also expressed high levels of T cell immunoglobulin mucin domain (TIM)4 and
      costimulatory molecules. High levels of Staphylococcal enterotoxin B (SEB) were
      detected in the AR nasal mucosa. Expression of TIM4 could be induced in naive B
      cells in the presence of SEB in culture. TIM4+ B cells could induce naive CD4+ T
      cells to differentiate into Th2 cells. CONCLUSIONS: TIM4+ B cells from AR nasal
      mucosa can induce skewed Th2 polarization. It may be a potential therapeutic
      target in the treatment of AR. B cells plays an important role in the initiation
      of Th2 polarization. KEY MESSAGES: * High frequency of B cells exists in nasal
      mucosa of allergic rhinitis * These B cells express high levels of TIM4 * TIM4+ B
      cells can initiate the skewed Th2 polarization.

PMID- 22454246
TI  - IDO-competent-DCs induced by IFN-gamma attenuate acute rejection in rat liver
      transplantation.
AB  - PURPOSE: We established a stable rat model of liver transplantation using Sprague
      Dawley rats and Wistar rats in order to investigate the role of the IDO gene in
      acute rejection after rat liver transplantation. METHODS: IDO gene expression and
      IDO enzyme activity were quantified in liver syngeneic grafts and allografts
      using microdialysis-HPLC. Liver allografts were evaluated for IDO expression by
      histopathology. We measured liver function-related biomarkers in liver allografts
      which were re-infused with untreated or IFN-gamma-treated dendritic cells (DCs).
      RESULTS: We found a significant increase in IDO gene expression and IDO enzyme
      activity in liver allografts compared the sham and syngeneic graft groups. There
      was a significant correlation between the number of IDO-positive cells and
      severity of acute rejection. IDO gene expression and enzyme activity was
      upregulated in the IFN-gamma-treated DC group within 7 days after transplantation
      compared to the untreated DC group and survival rates were significantly
      improved. CONCLUSIONS: Our results suggested that IDO gene expression correlates
      with the severity of acute rejection and that IFN-gamma-induced IDO-positive DCs
      may attenuate acute rejection and catalyze local tryptophan metabolism via IDO
      enzyme expression, leading to immune tolerance after liver transplantation.

PMID- 22454247
TI  - Type17 T-cells in central nervous system autoimmunity and tumors.
AB  - Interleukin-17 (IL-17) producing Type17 T-cells, specifically T-helper (Th)17
      cells reactive to central nervous system (CNS) autoantigens, manifest a higher
      migratory capability to the CNS parenchyma compared with other T-cell
      subpopulations due to their ability to penetrate the blood brain barrier (BBB).
      In the field of cancer immunotherapy, there are now a number of cell therapy
      approaches including early studies using T-cells transduced with chimeric antigen
      receptors in hematologic malignancy, suggesting that the use of T-cells or
      genetically modified T-cells could have a significant role in effective cancer
      therapy. However, the successful application of this strategy in solid tumors,
      such as CNS tumors, requires careful consideration of critical factors to improve
      the tumor-homing of T-cells. The current review is dedicated to discuss recent
      findings on the role of Type17 T-cells in CNS autoimmunity and cancer. The
      insight gained from these findings may lead to the development of novel
      therapeutic and prophylactic strategies for CNS autoimmunity and tumors.

PMID- 22454248
TI  - A meta-analysis of proximal occlusion device outcomes in carotid artery stenting.
AB  - BACKGROUND: The clinical risk predictors for adverse events in carotid stenting
      using distal embolic protection devices are well established and include patient
      age and symptomatic status. The risk predictors for adverse events with proximal
      occlusion devices are not as well established. This study is a meta-analysis of
      available data on proximal occlusion devices to determine the risk predictors of
      adverse events in carotid stenting. METHODS: Study-specific results on 2,397
      patients from six independent databases of two different proximal occlusion
      devices were meta-analyzed by an independent statistical analysis organization
      for predictors of 30-day major adverse clinical events including stroke,
      myocardial infarction, and death using random effects models. The primary
      endpoint was the composite of total stroke, myocardial infarction, and death at
      30 days. RESULTS: The incidence of stroke was 1.71%. The incidence of myocardial
      infarction was 0.02%. The incidence of death was 0.40%. The composite primary
      endpoint at 30 days was 2.25%. Age and diabetic status were found to be the only
      significant independent risk predictors; however, total stroke rates remained
      below 2.6% in all subgroups, including symptomatic octogenarians. The other
      baseline demographic variables including patient gender, symptomatic status, and
      contralateral carotid occlusion were not found to be independent risk predictors.
      CONCLUSIONS: A meta-analysis of CAS procedures performed with proximal occlusion
      devices demonstrated a very low incidence of adverse events at 30 days. The only
      independent risk predictors were age and diabetes. Patient gender, symptomatic
      status, and other baseline characteristics were not found to be risk predictors
      for CAS using proximal occlusion devices.

PMID- 22454249
TI  - Surveying uveitis specialists-a call for consensus.

PMID- 22454250
TI  - Disseminated tuberculosis presenting as irido-ciliary granuloma in an
      immunocompetent patient.

PMID- 22454251
TI  - Long-term efficacy and safety of asenapine or olanzapine in patients with
      schizophrenia or schizoaffective disorder: an extension study.
AB  - INTRODUCTION: Safety and efficacy results, collected in schizophrenia and
      schizoaffective disorder patients treated for up to nearly 3 years, are presented
      for asenapine and olanzapine. RESULTS: Patients completing a 52-week randomized
      double-blind core study on flexible-dose asenapine (5 or 10 mg BID) or olanzapine
      (10 or 20 mg QD) could continue treatment until study blind was broken.290
      patients on asenapine and 150 on olanzapine continued treatment for variable
      lengths of time [mean +/- SD (range) 311.0 +/- 146.1 (10 - 653) d and 327.4 +/-
      139.6 (15 - 631) d, respectively]. Adverse event (AE) incidence was lower during
      the extension (asenapine, 62%; olanzapine, 55%) than during the core study (78%,
      80%). In both groups, body weight increase and incidence of extrapyramidal AEs
      were negligible during the extension. Mean PANSS total score changes during first
      year of treatment were - 37.0 for asenapine and - 35.3 for olanzapine, with
      further changes of 1.6 for asenapine and - 0.8 for olanzapine at the extension
      study endpoint. CONCLUSIONS: Clinical stability on asenapine as well as
      olanzapine was maintained, with few recurrent or newly emerging AEs beyond 1 year
      of treatment.

PMID- 22454252
TI  - A study of brain and serum brain-derived neurotrophic factor protein in Wistar
      and Wistar-Kyoto rat strains after electroconvulsive stimulus.
AB  - BACKGROUND: Serum brain-derived neurotrophic factor (BDNF) protein has been
      related to depression and less consistently to its treatments in human studies.
      However, animal studies have failed to demonstrate a clear link between BDNF
      protein in serum and brain tissue. METHODS: Serum and brain tissue levels of BDNF
      protein were measured with ELISA in the Wistar-Kyoto (WKY) and Wistar strains at
      1 and 7 days after 5 daily electroconvulsive stimulus sessions or sham
      treatments. RESULTS: The WKY strain showed lower baseline serum BDNF protein
      relative to Wistar controls. After 5 electroconvulsive stimuli, BDNF protein
      density was significantly increased in hippocampus and cortical regions, but not
      in the cerebellum or in serum. A clear correlation between brain and serum BDNF
      was not observed in either strain or treatment group. DISCUSSION: Despite lower
      baseline serum BDNF protein in the WKY strain, a lack of change in serum BDNF
      after electroconvulsive stimulus and a lack of correlation between brain and
      serum BDNF protein calls into question the relevance of serum BDNF as a measure
      of depression and treatment response.

PMID- 22454253
TI  - Solution structures of the double-stranded RNA-binding domains from RNA helicase
      A.
AB  - RNA helicase A (RHA) is a highly conserved protein with multifaceted functions in
      the gene expression of cellular and viral mRNAs. RHA recognizes highly structured
      nucleotides and catalytically rearranges the various interactions between RNA,
      DNA, and protein molecules to provide a platform for the ribonucleoprotein
      complex. We present the first solution structures of the double-stranded RNA
      binding domains (dsRBDs), dsRBD1 and dsRBD2, from mouse RHA. We discuss the
      binding mode of the dsRBDs of RHA, in comparison with the known dsRBD structures
      in their complexes. Our structural data provide important information for the
      elucidation of the molecular reassembly mediated by RHA.

PMID- 22454255
TI  - Extraordinary radical scavengers: 4-mercaptostilbenes.
AB  - In the past decade, there was a great deal of interest and excitement in
      developing more active antioxidants and cancer chemoprevention agents than
      resveratrol, a naturally occurring stilbene. In this work, eight resveratrol
      directed 4-mercaptostilbenes were constructed based on the inspiration that
      thiophenol should be a stronger radical scavenger than phenol, and their reaction
      rates with galvinoxyl (GO(.)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(.))
      radicals in methanol and ethyl acetate were measured by using stopped-flow UV/Vis
      spectroscopy at 25  degrees C. Kinetic analysis demonstrates that 4
      mercaptostilbenes are extraordinary radical scavengers, and the substitution of
      the 4-SH group for the 4-OH group in the stilbene scaffold is an important
      strategy to improve the radical-scavenging activity of resveratrol. Surprisingly,
      in methanol, some of the 4-mercaptostilbenes are 10(4)-times more active than
      resveratrol, dozens of times to hundreds of times more effective than known
      antioxidants (alpha-tocopherol, ascorbic acid, quercetin, and trolox). The
      detailed radical-scavenging mechanisms were discussed based on acidified-kinetic
      analysis. Addition of acetic acid remarkably reduced the GO(.) and DPPH(.)
      radical-scavenging rates of the 4-mercaptostilbenes in methanol, a solvent that
      supports ionization, suggesting that the reactions proceed mainly through a
      sequential proton loss electron transfer mechanism. In contrast, an interesting
      acid-promoted kinetics was observed for the reactions of the 4-mercaptostilbenes
      with DPPH(.) in ethyl acetate, a solvent that weakly supports ionization. The
      increased ratio in rates is closely correlated with the electron-rich environment
      in the molecules, suggesting that the acceleration could benefit from the
      contribution of the electron transfer from the 4-mercaptostilbenes and DPPH(.).
      However, the addition of acetic acid had no influence on the GO(.)-scavenging
      rates of the 4-mercaptostilbenes in ethyl acetate, due to the occurrence of the
      direct hydrogen atom transfer. Our results show that the radical-scavenging
      activity and mechanisms of 4-mercaptostilbenes depends significantly on the
      molecular structure and acidity, the nature of the attacking radical, and the
      ionizing capacity of the solvent.

PMID- 22454257
TI  - Efficient functional delivery of siRNA using mesoporous silica nanoparticles with
      ultralarge pores.
AB  - Among various nanoparticles, mesoporous silica nanoparticles (MSNs) have
      attracted extensive attention for developing efficient drug-delivery systems,
      mostly due to their high porosity and biocompatibility. However, due to the small
      pore size, generally below 5 nm in diameter, potential drugs that are loaded into
      the pore have been limited to small molecules. Herein, a small interfering RNA
      (siRNA) delivery strategy based on MSNs possessing pores with an average diameter
      of 23 nm is presented. The siRNA is regarded as a powerful gene therapeutic agent
      for treatment of a wide range of diseases by enabling post-transcriptional gene
      silencing, so-called RNA interference. Highly efficient, sequence-specific, and
      technically very simple target gene knockdown is demonstrated using MSNs with
      ultralarge pores of size 23 nm in vitro and in vivo without notable cytotoxicity.

PMID- 22454254
TI  - Nuclear IRS-1 and cancer.
AB  - The family of insulin receptor substrates (IRS) consists of four proteins (IRS-1
      IRS-4), which were initially characterized as typical cytosolic adaptor proteins
      involved in insulin receptor (IR) and insulin-like growth factor I receptor (IGF
      IR) signaling. The first cloned and characterized member of the IRS family, IRS
      1, has a predicted molecular weight of 132 kDa, however, as a result of its
      extensive serine phosphorylation it separates on a SDS gel as a band of
      approximately 160-185 kDa. In addition to its metabolic and growth-promoting
      functions, IRS-1 is also suspected to play a role in malignant transformation.
      The mechanism by which IRS-1 supports tumor growth is not fully understood, and
      the argument that IRS-1 merely amplifies the signal from the IGF-1R and/or IR
      requires further investigation. Almost a decade ago, we reported the presence of
      nuclear IRS-1 in medulloblastoma clinical samples, which express viral
      oncoprotein, large T-antigen of human polyomavirus JC (JCV T-antigen). This first
      demonstration of nuclear IRS-1 was confirmed by several other laboratories.
      Nuclear IRS-1 was also detected by cells expressing the SV40 T-antigen, v-Src, in
      immortalized fibroblasts stimulated with IGF-I, in hepatocytes, 32D cells, and in
      an osteosarcoma cell line. More recently, nuclear IRS-1 was detected in breast
      cancer cells in association with estrogen receptor alpha (ERalpha), and in JC
      virus negative medulloblastoma cells expressing estrogen receptor beta (ERbeta),
      further implicating nuclear IRS-1 in cellular transformation. Here, we discuss
      how nuclear IRS-1 acting on DNA repair fidelity, transcriptional activity, and
      cell growth can support tumor development and progression.

PMID- 22454256
TI  - Outcomes and prognostic factors in gallbladder cancer: a single-centre
      experience.
AB  - INTRODUCTION: Gallbladder cancer is the most common malignant tumour of the
      biliary system with an extraordinarily poor prognosis. In this study, we
      retrospectively evaluated forty-two patients with histologically proven
      gallbladder cancer. PATIENTS AND METHODS: Estimated survival rates were
      calculated by the Kaplan-Meier method, and differences were assessed using the
      logrank test. The GKR (combined registry of cancer) and demographic data were
      used to gain information on community cancer statistics. RESULTS: In this study,
      patients with metastases showed poorer survival rates. Furthermore, the survival
      was significantly better in patients with R0 resections, smaller tumour sizes and
      without lymph node infiltration. T stage, M stage and R stage were independent
      prognostic parameters. Sex and age had no significant effect on survival. Also,
      we found that patients with incidental gallbladder cancer and those with
      cholecystolithiasis showed significantly better survival rates. Demographic
      analyses of the study group confirmed a high coverage of our institution for
      incident cases in our catchment area and no significant regional deviations from
      the expected incidence of gallbladder cancer. CONCLUSION: Despite differences in
      the incidence in different geographical areas, gallbladder cancer appears to be
      fairly normally distributed in Western Pomerania, a predominantly rural area of
      Northeastern Germany. Coverage of incident cases in our catchment area was high.
      T stage, M stage and R stage were independent prognostic factors in our study. We
      conclude that, whenever possible, an R0 resection should be the surgical goal in
      all patients staged resectable before surgery, but heroic resections in patients
      with highly advanced cancer disease or severe accompanying non-tumour diseases
      are not warranted.

PMID- 22454258
TI  - Predicting the discharge status after liver transplantation at a single center: a
      new approach for a new era.
AB  - The aim of this study was to develop a tool for preoperatively predicting the
      need of a patient to attend an extended care facility after orthotopic liver
      transplantation (OLT). A multidisciplinary group, which included 2 transplant
      surgeons, 2 transplant nurses, 1 nurse manager, 2 physical therapists, 1 case
      manager, 1 home health care professional, 1 rehabilitation physician, and 1
      statistician, met to identify preoperative factors relevant to discharge
      planning. The parameters that were examined as potential predictors of the
      discharge status were as follows: age, sex, language, Karnofsky score, OLT alone
      (versus a combined procedure), creatinine, bilirubin, international normalized
      ratio (INR), albumin, body mass index (BMI), Child-Turcotte-Pugh score, chemical
      Model for End-Stage Liver Disease score, renal dialysis, location before
      transplantation, comorbidities (encephalopathy, ascites, hydrothorax, and
      hepatopulmonary syndrome), diabetes mellitus (DM), cardiac ejection fraction and
      right ventricular systolic pressure, sex and availability of the primary
      caregiver, donor risk index, and donor characteristics. Between January 2004 and
      April 2010, 730 of 777 patients (94%) underwent only liver transplantation, and
      47 patients (6%) underwent combined procedures. Five hundred nineteen patients
      (67%) were discharged home, 215 (28%) were discharged to a facility, and 43 (6%)
      died early after OLT. A multivariate logistic regression analysis identified the
      following parameters as significantly influencing the discharge status: a low
      Karnofsky score, an older age, female sex, an INR of 2.0, a creatinine level of
      2.0 mg/dL, DM, a high bilirubin level, a low albumin level, a low or high BMI,
      and renal dialysis before OLT. The nomogram was prospectively validated with a
      population of 126 OLT recipients with a concordance index of 0.813. In
      conclusion, a new approach to improving the efficiency of hospital care is
      essential. We believe that this tool will aid in reducing lengths of stay and
      improving the experience of patients by facilitating early discharge planning.

PMID- 22454259
TI  - Engaging African-Americans about biobanks and the return of research results.
AB  - We conducted a deliberative engagement to assess attitudinal changes regarding
      biobank research, governance, and the return of results. We recruited African
      Americans from two Southside Chicago health care facilities that serve
      communities of very different socioeconomic and educational backgrounds in order
      to examine similarities and differences within the African-American population.
      We used a mixed method, deliberative engagement process involving a convenience
      sample of parents recruited from a Federally Qualified Health Clinic (FQHC) [n =
      23] and a university-based practice (UBP) [n = 22]. Four coding categories
      illustrate similarities and differences between participants from the two
      different practices: (1) reasons for and against participation; (2) trust and
      mistrust; (3) return of research results; and (4) religion. Overall, there was
      strong interest in receiving results, which was a main motivator for
      participation. While participants from both health care facilities expressed
      distrust of research, UBP participants also expressed trust in the research
      enterprise. FQHC participants more frequently mentioned religion. Studies about
      participation in biobanks often focus on participants' race as the sole
      significant variable, while our work supports the importance of other demographic
      factors. Medical researchers must move beyond research analyses that consider the
      African-American population to be monolithic and value the diversity within it.

PMID- 22454260
TI  - [Urooncology: who is competent?].

PMID- 22454261
TI  - [Practical information on the use of port systems].
AB  - As a result of the dynamic developments in oncology over the last few years,
      multimodal therapeutic options are now available for the treatment of cancer
      patients in practically all diseases stages. This has led to an increase in the
      use of all forms of chemotherapy. Low and moderately complex chemotherapy options
      are being increasingly employed in outpatient and day clinic settings. For this
      reason, among others, the implantation of central venous port systems has
      progressed to become an important component in the therapeutic planning for
      oncological patients.

PMID- 22454262
TI  - [Tumour registry and reality: differential diagnosis of testicular tumours in
      childhood: survey and personal experience].
AB  - Painless scrotal swelling must always be considered as a potential malignant
      testicular tumour until proven otherwise. Prepubertal testicular tumours are
      seldom entities, for their differential diagnosis testicular sonography is
      gaining increasing importance. Although, according to national and international
      tumour registries, most patients tend to have malignant tumours, some clinical
      series from paediatric centres confirm that prepubertal testicular tumours are
      mainly benign lesions, especially up to the age of 12 years. Testis-sparing
      procedures are favoured when AFP is in a normal range and testicular parenchyma
      is detected sonographically. Oncological principles should be applied to
      paediatric patients consequently, staging examinations should be requested when a
      definite histology is proven. Cases should be reported to national tumour
      registries and, in addition to close surveillance, in some cases adjuvant therapy
      is necessary. In addition to the clinical guidelines from the tumour registries,
      differential diagnosis, testis-sparing surgery and the presence of TIN in the
      paediatric population should be discussed.

PMID- 22454263
TI  - [Anti-inflammatory drugs and prostatic carcinoma: current state of evidence].
AB  - The epidemiological evidence for a protective effect of anti-inflammatory drugs
      against prostatic carcinoma is suggestive but not conclusive. Studies are limited
      by inadequate information on dose and duration of use and by methodological
      biases. Furthermore, potential benefits should be weighed against the known side
      effects of long-term use.

PMID- 22454264
TI  - [Sigmoid-rectum pouch: a modification of the ureterosigmoidostomy].

PMID- 22454266
TI  - Ag nanobelts: synthesis, morphological evolution, and their use as
      electrocatalysts for oxygen reduction.
AB  - The recent development of 1D nanomaterials of controllable size, composition, and
      structure has opened up enormous possibilities for engineering catalysts with
      enhanced activity and selectivity. Herein, we report a one-step strategy for the
      fabrication of versatile silver nanomaterials. Tailored structures, such as
      nanobelts, nanowires, and nanocables, were conveniently synthesized by adjusting
      the reaction conditions. The novelty of this synthesis is in a one-pot procedure
      that combines the sequential formation of precursor nucleation, in situ
      polymerization, and crystal shaping under mild conditions. The as-synthesized
      cables consisted of a metallic core (Ag) and an organic outer shell (poly(o
      anisidine), POA). Control experiments demonstrated that the introduced organic
      monomer (OA) not only acted as the nanoreactor and capping agent, but also a
      modest reducer for controlled crystal growth at the hydrophilic interface.
      Electrocatalytic tests showed enhanced stability and activity towards the
      reduction of oxygen, which was believed to be closely associated with the core
      shell structural characteristics of the nanomaterials. Their electrocatalytic
      performance and tunable structure makes such silver nanobelts promising
      candidates for applications in catalysis and as sensors in nanoelectrochemical
      devices.

PMID- 22454267
TI  - Stroke in sub-Saharan Africa: an urgent call for prevention.

PMID- 22454268
TI  - Evidence-based guideline: intravenous immunoglobulin in the treatment of
      neuromuscular disorders: report of the Therapeutics and Technology Assessment
      Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To assess the evidence for the efficacy of IV immunoglobulin (IVIg) to
      treat neuromuscular disorders. METHODS: The MEDLINE, Web of Science, and EMBASE
      databases were searched (1966-2009). Selected articles were rated according to
      the American Academy of Neurology's therapeutic classification of evidence
      scheme; recommendations were based on the evidence level. RESULTS AND
      RECOMMENDATIONS: IVIg is as efficacious as plasmapheresis and should be offered
      for treating Guillain-Barre syndrome (GBS) in adults (Level A). IVIg is effective
      and should be offered in the long-term treatment of chronic inflammatory
      demyelinating polyneuropathy (Level A). IVIg is probably effective and should be
      considered for treating moderate to severe myasthenia gravis and multifocal motor
      neuropathy (Level B). IVIg is possibly effective and may be considered for
      treating nonresponsive dermatomyositis in adults and Lambert-Eaton myasthenic
      syndrome (Level C). Evidence is insufficient to support or refute use of IVIg in
      the treatment of immunoglobulin M paraprotein-associated neuropathy, inclusion
      body myositis, polymyositis, diabetic radiculoplexoneuropathy, or Miller Fisher
      syndrome, or in the routine treatment of postpolio syndrome or in children with
      GBS (Level U). IVIg combined with plasmapheresis should not be considered for
      treating GBS (Level B). More data are needed regarding IVIg efficacy as compared
      with other treatments/treatment combinations. Most studies concluded IVIg-related
      serious adverse effects were rare. Given the variable nature of these diseases,
      individualized treatments depending on patient need and physician judgment are
      important.

PMID- 22454269
TI  - Fixing the broken system of genetic locus symbols: Parkinson disease and dystonia
      as examples.
AB  - Originally, locus symbols (e.g., DYT1) were introduced to specify chromosomal
      regions that had been linked to a familial disorder with a yet unknown gene.
      Symbols were systematically assigned in a numerical series to designate mapped
      loci for a specific phenotype or group of phenotypes. Since the system of
      designating and using locus symbols was originally established, both our
      knowledge and our techniques of gene discovery have evolved substantially. The
      current system has problems that are sources of confusion, perpetuate
      misinformation, and misrepresent the system as a useful reference tool for a list
      of inherited disorders of a particular phenotypic class. These include
      erroneously assigned loci, duplicated loci, missing symbols, missing loci,
      unconfirmed loci in a consecutively numbered system, combining causative genes
      and risk factor genes in the same list, and discordance between phenotype and
      list assignment. In this article, we describe these problems and their impact,
      and propose solutions. The system could be significantly improved by creating
      distinct lists for clinical and research purposes, creating more informative
      locus symbols, distinguishing disease-causing mutations from risk factors,
      raising the threshold of evidence prior to assigning a locus symbol, paying
      strict attention to the predominant phenotype when assigning symbols lists, and
      having a formal system for reviewing and continually revising the list that
      includes input from both clinical and genetics experts.

PMID- 22454270
TI  - Neurology and neurologic practice in China.

PMID- 22454271
TI  - Vision for a digital future: getting personal.

PMID- 22454272
TI  - Teaching neuroimages: an unusual case of syncope.

PMID- 22454273
TI  - Teaching neuroimages: rib penciling and intraspinal dislocation of rib heads in
      type 1 neurofibromatosis.

PMID- 22454274
TI  - Hospitalization and effects on cognition.

PMID- 22454275
TI  - Variations of the analgesia nociception index during general anaesthesia for
      laparoscopic abdominal surgery.
AB  - The analgesia nociception index (ANI) is an online heart rate variability
      analysis proposed for assessment of the antinociception/nociception balance. In
      this observational study, we compared ANI with heart rate (HR) and systolic blood
      pressure (SBP) during various noxious stimuli in anaesthetized patients. 15 adult
      patients undergoing laparoscopic appendectomy or cholecystectomy were studied.
      Patients received target controlled infusions of propofol (adjusted to maintain
      the Bispectral index in the range [40-60]) and remifentanil (with target increase
      in case of haemodynamic reactivity [increase in HR and/or SBP >20% of baseline]),
      and cisatracurium. Medical staff was blind to the ANI monitor. ANI and
      haemodynamic data were recorded at predefined times before and during surgery,
      including tetanic stimulation of the ulnar nerve before start of surgery.
      Anaesthesia induction decreased HR and SBP, while high ANI values (88 [17]) were
      recorded, indicating parasympathetic predominance. In 10 out of 11 patients,
      tetanic stimulation led to a transient (<5 min) decrease in ANI to 48 (40)
      whereas HR and SBP did not change. After start of surgery, ANI decreased to 60
      (39) and decreased further to 50 (15) after the pneumoperitoneum was inflated,
      while there was no significant change in HR or SBP. When haemodynamic reactivity
      occurred, ANI had further decreased to 40 (15). After completion of surgery, ANI
      returned to 90 (34). ANI seems more sensitive than HR and SBP to moderate
      nociceptive stimuli in propofol-anaesthetized patients. Whether ANI monitoring
      may allow preventing haemodynamic reactivity to noxious stimuli remains to be
      demonstrated.

PMID- 22454276
TI  - An evaluation of the Integrated Pulmonary Index (IPI) for the detection of
      respiratory events in sedated patients undergoing colonoscopy.
AB  - The Integrated Pulmonary Index (IPITM) is a new decision making tool calculated
      from measured end tidal carbon dioxide (etCO(2)), respiratory rate (RR), oxygen
      saturation (SpO(2)) and pulse rate (PR) using a fuzzy logic model. The aim of
      this study was to compare prospectively IPI to respiratory adverse events in
      patients undergoing moderate sedation for colonoscopy. Following ethics committee
      approval and personal informed consent 51 adult patients undergoing elective
      colonoscopy were enrolled. Patients received routine care by the endoscopy staff
      that were blinded to IPI, etCO(2), and RR; whilst a trained senior
      anesthesiologist observer, not involved in the procedure, collected this data.
      'Requires attention' respiratory adverse events (at least 1 min of SpO(2) <= 92 %
      and/or RR <= 8 and or 20 % decrease in etCO(2)) and 'requires intervention'
      respiratory adverse events (at least 1 min of SpO(2) <= 85 % and/or RR = 0) were
      documented by the observer. There were no differences in etCO(2), RR, SpO(2) and
      PR between 5778 IPI readings ranging from 1 to 10. Low (1-3), medium (4-6) and
      high (7-10) IPI groups did not differ in RR, SpO(2) and PR, but etCO(2) was
      higher in the high IPI group (p = 0.0185). Among requires attention events (n =
      113) the IPI was high (7-10) in 53.1 %, intermediate (4-6) in 32.7 %, or low (1
      3) in 14.2 %. The presented data demonstrate limited agreement between
      respiratory physiological parameters and the IPI. Further IPI evaluation and
      validation is indicated mainly for events requiring immediate intervention and in
      different patient populations including obese patients.

PMID- 22454277
TI  - Granum-like stacking structures with TiO2 -graphene nanosheets for improving
      photo-electric conversion.
AB  - Solar energy is commonly considered to be one of the most important forms of
      future energy production. This is due to its ability to generate essentially free
      power, after installation, with low environmental impact. Green plants,
      meanwhile, exhibit a process for light-to-charge conversion that provides a
      useful model for using solar radiation efficiently. Granum, the core organ in
      photosynthesis consists of a stack of ~10-100 thylakoids containing pigments and
      electrons acceptors. Imitating the structure and function of granum, stacked
      structures are fabricated with TiO(2) /graphene nanosheets as the thylakoids
      unit, and their photo-electric effect is studied by varying the number of layers
      present in the film. The photo-electric response of the graphene composites are
      found to be 20 times higher than that of pure TiO(2)  in films with 25 units
      stacked. Importantly, the cathodic photocurrent changes to anodic photocurrent as
      the thickness increases, an important feature of efficient solar cells which is
      often ignored. Here graphene is proposed to perform similarly to the b6f complex
      in granum, by separating charges and transporting electrons through the stacked
      film. Using this innovation, stacked TiO(2) /graphene structures are now able to
      significantly increase photoanode thickness in solar cells without losing the
      ability to conduct electrons.

PMID- 22454278
TI  - Growth of highly oriented hydroxyapatite arrays tuned by quercetin.
AB  - Crystal calls: the remarkable crystal modulation ability of quercetin (QUE) in
      highly oriented hydroxyapatite (HAp) array crystallization is reported. Organized
      HAp crystals were obtained by hydrothermal exchange of alpha-tricalcium phosphate
      (alpha-TCP) precursor in solution with a progressive increase in QUE
      concentration. Experimental results revealed that QUE would be a potentially
      effective crystal modulation assistant.

PMID- 22454279
TI  - Patterned functional carbon fibers from polyethylene.
AB  - Carbon fibers having unique morphologies, from hollow circular to gear-shaped,
      are produced from a novel melt-processable precursor and method. The resulting
      carbon fiber exhibits microstructural and topological properties that are
      dependent on processing conditions, rendering them highly amenable to myriad
      applications.

PMID- 22454280
TI  - Intentional use of Schistosoma mansoni-infected grafts in living donor liver
      transplantation.

PMID- 22454281
TI  - [Genetic diversity and bone marrow transplantation].
AB  - The genetic origin of the patients, for whom a bone marrow transplantation has
      been proposed, is a key determinant in the possibility of identifying or not a
      compatible unrelated donor, and consequently in the possibility of performing the
      bone marrow transplantation. The required strict HLA compatibility, in the
      context of a bone marrow transplantation, increases the difficulty. A patient has
      one chance over four to have a compatible donor within his brothers and sisters,
      if any. This chance becomes one over a million, as an average, in the context of
      unrelated donor search. Taking into consideration the genetic history of the
      populations, their evolution and the large actual HLA diversity, the probability
      of finding an unrelated donor for a defined patient varies according to the
      frequency and the combination of the patient's HLA antigens, genetic markers
      inherited not only from his parents, but also from his ancestries. In the
      unrelated context, the HLA compatible donor most probably shares the same genetic
      history than the patient, and consequently belongs to the same population group.
      The study of the genetic of populations explains the difficulties in finding an
      unrelated compatible donor in the migrant populations, particularly those
      originated from Africa and from the middle east, due to their HLA specificities
      and to the small number of donors sharing the same origins registered on a
      volunteer bone marrow donors' file worldwide.

PMID- 22454282
TI  - Confirmation of drug delivery after liver chemoembolization: direct tissue
      doxorubicin measurement by UHPLC-MS-MS.
AB  - Because liver cancer is rarely suitable for surgery, transcatheter arterial
      chemoembolization (TACE) is used for palliative therapy. In this procedure, an
      emulsion of doxorubicin in iodized oil is injected directly into liver tumors
      through a catheter positioned within the artery supplying blood flow to the
      tumor. At present, there is limited understanding of factors affecting the
      delivery and dispersion of doxorubicin within treated tumors during TACE. This
      study addresses the development and application of an ultrahigh-pressure liquid
      chromatography-tandem mass spectrometry (UHPLC-MS-MS) method for rapid
      confirmation of drug delivery after TACE in a rabbit VX2 liver cancer model.
      Doxorubicin levels in liver tumors were measured using UHPLC-MS-MS and compared
      with computed tomography measured levels of iodized oil, a metric used clinically
      to indicate drug delivery. We found that tissue drug levels determined using
      UHPLC-MS-MS did not correlate with the regional iodized oil concentration
      (vehicle) within tumors following TACE, suggesting that chemotherapeutic drugs
      like doxorubicin spread throughout tumors, and that lack of iodized oil staining
      in portions of a tumor does not necessarily indicate inadequate therapy during
      TACE.

PMID- 22454283
TI  - Identification and characterization of two general odorant binding protein genes
      from the oriental fruit moth, Grapholita molesta (busck).
AB  - Two novel general odorant-binding protein (GOBP) cDNAs (GmolGOBP1 and GmolGOBP2)
      were cloned and characterized from female antennal tissue of the oriental fruit
      moth, Grapholita molesta. We focused our investigation on this olfactory protein
      family by using reverse transcription-polymerase chain reaction (RT-PCR) and
      rapid amplification of cDNA ends-PCR (RACE-PCR). The full-length open reading
      frames of GmolGOBP1 and GmolGOBP2 were 492 and 483 nucleotides long, which encode
      164 and 161 amino acid residue peptides, respectively. Protein signature analyses
      revealed that they each contained six conserved cysteines with an N-terminal
      signal sequence of 20 amino acids. The alignment of the two deduced protein
      sequences with other Lepidoptera GOBPs showed high sequence similarity (70-80%)
      with other full-length sequences from GenBank. Sequence similarity between the
      two GOBPs was only 48%, suggesting that the two proteins belong to different
      classes of lepidopteran GOBPs. RT-PCR analysis revealed that the two GOBP genes
      were expressed only in antennae of both sexes. Real-time PCR analysis further
      indicated that the transcript level of GmolGOBP1 was higher in males than in
      females, whereas the transcript level of GmolGOBP2 was higher in females than in
      males. Temporally, the two GOBP genes were expressed during the complete
      photoperiod (15L:9D). The highest transcript levels of GmolGOBP1 in both sexes
      and GmolGOBP2 in females were detected at the end of photophase and during
      scotophase. The expression of GmolGOBP2 in males remained at similar levels
      during the complete photoperiod. Based on these results, the possible
      physiological functions of GmolGOBPs are discussed.

PMID- 22454284
TI  - Heparin interacting protein mediated assembly of nano-fibrous hydrogel scaffolds
      for guided stem cell differentiation.
AB  - A new methodology is developed to conjugate hyaluronic acid (HA) hydrogel with
      novel nano-fibrous architectures via non-covalent assembly that specifically
      allows for targeted adipose-derived stem cells (ASCs) differentiation and soft
      tissue engineering. The assembly of non-covalently associated hydrogel network
      produced via the interaction of a low molecular weight heparin (LMWH) modified HA
      derivative and heparin interacting protein (HIP). The multifunctional star
      poly(ethylene glycol) (PEG) and HIP copolymer has the capability to mediate the
      non-covalent assembly of nano-fibrous HA hydrogel networks via affinity
      interactions with LMWH. The effect of the HIP mediation on in vitro gelation,
      rheological characteristics, degradation, equilibrium swelling, adipose-derived
      stem cells (ASCs) proliferation and differentiation of nano-fibrous hydrogel is
      examined. The results suggest the potential utility of this unique design of the
      bioactive nano-fibrous HA hydrogel in directing the differentiation of ASCs and
      adipogenesis in ECM-mimetic scaffolds in vitro. These studies demonstrate that
      this nano-fibrous HA hydrogel can render the formulation of a therapeutically
      effective platform for in vitro adipogenesis applications.

PMID- 22454285
TI  - Continued importance of family factors in youth smoking behavior.
AB  - INTRODUCTION: Although it is known that levels of family factors (FF) such as
      parental monitoring and parent-adolescent connectedness vary during adolescence,
      it is unknown which factors remain protective, preventing smoking initiation, in
      youth of differing racial/ethnic groups. Using a longitudinal, nationally
      representative sample, we examined which FF protect against smoking initiation in
      White, Black, and Hispanic youth. METHODS: A total of 3,473 parent-nonsmoking
      youth dyads from Round 1 (T1) of the National Survey of Parents and Youth were
      followed to Round 3 (T2). Youth smoking status at T2 was assessed as the primary
      outcome. We examined changes in FF (T2 - T1) and the protection afforded by these
      factors at T1 and T2 for smoking initiation, both by race/ethnicity and overall.
      RESULTS: There were statistically significant decreases in levels of protective
      FF from T1 to T2 across all racial/ethnic groups; however, FF levels were higher
      in never-smokers compared with smoking initiators at both T1 and T2 (p < .05).
      Separate models by race/ethnicity showed the protective effect of increased
      perceived punishment in all racial/ethnic groups and protection against
      initiation by increased parental monitoring in Black and Hispanic youth. Overall,
      higher parental monitoring at T1 was associated with decreased odds of smoking
      initiation (33%); decreased parental monitoring and perceived punishment from T1
      to T2 were associated with increased odds of smoking initiation (55% and 17%,
      respectively). CONCLUSIONS: Smoking prevention interventions should encourage
      parents to both enforce consistent consequences of smoking behavior, and continue
      monitoring, especially in minority groups.

PMID- 22454286
TI  - Real-time monitoring of rare circulating hepatocellular carcinoma cells in an
      orthotopic model by in vivo flow cytometry assesses resection on metastasis.
AB  - The fate of circulating tumor cells (CTC) is an important determinant of
      metastasis and recurrence, which leads to most deaths in hepatocellular carcinoma
      (HCC). Therefore, quantification of CTCs proves to be an emerging tool for
      diagnosing, stratifying, and monitoring patients with metastatic diseases. In
      vivo flow cytometry has the capability to monitor the dynamics of fluorescently
      labeled CTCs continuously and noninvasively. Here, we combine in vivo flow
      cytometry technique and a GFP-transfected HCC orthotopic metastatic tumor model
      to monitor CTC dynamics. Our in vivo flow cytometry has approximately 1.8-fold
      higher sensitivity than whole blood analysis by conventional flow cytometry. We
      found a significant difference in CTC dynamics between orthotopic and
      subcutaneous tumor models. We also investigated whether liver resection promotes
      or restricts hematogenous metastasis in advanced HCC. Our results show that the
      number of CTCs and early metastases decreases significantly after the resection.
      The resection prominently restricts hematogenous metastasis and distant
      metastases. CTC dynamics is correlated with tumor growth in our orthotopic tumor
      model. The number and size of distant metastases correspond to CTC dynamics. The
      novel in vivo flow cytometry technique combined with orthotopic tumor models
      might provide insights to tumor hematogenous metastasis and guidance to cancer
      therapy.

PMID- 22454288
TI  - Validity of triple- and dual-tracer techniques to estimate glucose appearance.
AB  - The triple-tracer (TT) dilution technique has been proposed to be the gold
      standard method to measure postprandial glucose appearance. However, validation
      against an independent standard has been missing. We addressed this issue and
      also validated the simpler dual-tracer (DT) technique. Sixteen young subjects
      with type 1 diabetes (age 19.5 +/- 3.8 yr, BMI 23.4 +/- 1.5 kg/m(2), HbA(1c) 8.7
      +/- 1.7%, diabetes duration 9.0 +/- 6.9 yr, total daily insulin 0.9 +/- 0.2 U.kg(
      1).day(-1), mean +/- SD) received a variable intravenous 20% dextrose infusion
      enriched with [U-(13)C]glucose over 8 h to achieve postprandial-resembling
      glucose excursions while intravenous insulin was administered to achieve
      postprandial-resembling levels of plasma insulin. Primed [6,6-(2)H(2)]glucose was
      infused in a manner that mimicked the expected endogenous glucose production and
      [U-(13)C; 1,2,3,4,5,6,6-(2)H(7)]glucose was infused in a manner that mimicked the
      expected glucose appearance from a standard meal. Plasma glucose enrichment was
      measured by gas chromatography-mass spectrometry. The intravenous dextrose
      infusion served as an independent standard and was reconstructed using the TT and
      DT techniques with the two-compartment Radziuk/Mari model and an advanced
      stochastic computational method. The difference between the infused and
      reconstructed dextrose profile was similar for the two methods (root mean square
      error 6.6 +/- 1.9 vs. 8.0 +/- 3.5 MUmol.kg(-1).min(-1), TT vs. DT, P = NS, paired
      t-test). The TT technique was more accurate in recovering the overall dextrose
      infusion (100 +/- 9 and 92 +/- 12%; P = 0.02). The root mean square error
      associated with the mean dextrose infusion profile was 2.5 and 3.3 MUmol.kg(
      1).min(-1) for the TT and DT techniques, respectively. We conclude that the TT
      and DT techniques combined with the advanced computational method can measure
      accurately exogenous glucose appearance. The TT technique tends to outperform
      slightly the DT technique, but the latter benefits from reduced experimental and
      computational complexity.

PMID- 22454287
TI  - Prolonged infusion of amino acids increases leucine oxidation in fetal sheep.
AB  - Maternal high-protein supplements designed to increase birth weight have not been
      successful. We recently showed that maternal amino acid infusion into pregnant
      sheep resulted in competitive inhibition of amino acid transport across the
      placenta and did not increase fetal protein accretion rates. To bypass placental
      transport, singleton fetal sheep were intravenously infused with an amino acid
      mixture (AA, n = 8) or saline [control (Con), n = 10] for ~12 days during late
      gestation. Fetal leucine oxidation rate increased in the AA group (3.1 +/- 0.5
      vs. 1.4 +/- 0.6 MUmol.min(-1).kg(-1), P < 0.05). Fetal protein accretion (2.6 +/-
      0.5 and 2.2 +/- 0.6 MUmol.min(-1).kg(-1) in AA and Con, respectively), synthesis
      (6.2 +/- 0.8 and 7.0 +/- 0.9 MUmol.min(-1).kg(-1) in AA and Con, respectively),
      and degradation (3.6 +/- 0.6 and 4.5 +/- 1.0 MUmol.min(-1).kg(-1) in AA and Con,
      respectively) rates were similar between groups. Net fetal glucose uptake
      decreased in the AA group (2.8 +/- 0.4 vs. 3.9 +/- 0.1 mg.kg(-1).min(-1), P <
      0.05). The glucose-O(2) quotient also decreased over time in the AA group (P <
      0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon
      increased in the AA group (119 +/- 24 vs. 59 +/- 9 pg/ml, P < 0.05), and
      norepinephrine (NE) also tended to increase in the AA group (785 +/- 181 vs. 419
      +/- 76 pg/ml, P = 0.06). Net fetal glucose uptake rates were inversely
      proportional to fetal glucagon (r(2) = 0.38, P < 0.05), cortisol (r(2) = 0.31, P
      < 0.05), and NE (r(2) = 0.59, P < 0.05) concentrations. Expressions of components
      in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle
      were similar between groups. In summary, prolonged infusion of amino acids
      directly into normally growing fetal sheep increased leucine oxidation. Amino
      acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a
      shift in substrate oxidation by the fetus from glucose to amino acids.

PMID- 22454289
TI  - Effects of methyl-deficient diets on methionine and homocysteine metabolism in
      the pregnant rat.
AB  - Although the importance of methyl metabolism in fetal development is well
      recognized, there is limited information on the dynamics of methionine flow
      through maternal and fetal tissues and on how this is related to circulating
      total homocysteine concentrations. Rates of homocysteine remethylation in
      maternal and fetal tissues on days 11, 19, and 21 of gestation were measured in
      pregnant rats fed diets with limiting or surplus amounts of folic acid and
      choline at two levels of methionine and then infused with L-[1-(13)C,(2)H(3)
      methyl]methionine. The rate of homocysteine remethylation was highest in maternal
      liver and declined as gestation progressed. Diets deficient in folic acid and
      choline reduced the production of methionine from homocysteine in maternal liver
      only in the animals fed a methionine-limited diet. Throughout gestation, the
      pancreas exported homocysteine for methylation within other tissues. Little or no
      methionine cycle activity was detected in the placenta at days 19 and 21 of
      gestation, but, during this period, fetal tissues, especially the liver,
      synthesized methionine from homocysteine. Greater enrichment of homocysteine in
      maternal plasma than placenta, even in animals fed the most-deficient diets,
      shows that the placenta did not contribute homocysteine to maternal plasma.
      Methionine synthesis from homocysteine in fetal tissues was maintained or
      increased when the dams were fed folate- and choline-deficient methionine
      restricted diets. This study shows that methyl-deficient diets decrease the
      remethylation of homocysteine within maternal tissues but that these rates are
      protected to some extent within fetal tissues.

PMID- 22454290
TI  - Deletion of prolyl carboxypeptidase attenuates the metabolic effects of diet
      induced obesity.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) is a critical regulator of
      energy metabolism. Prolyl carboxypeptidase (PRCP) is an enzyme responsible for
      its degradation and inactivation. PRCP-null mice (PRCP(gt/gt)) showed elevated
      levels of brain alpha-MSH, reduced food intake, and a leaner phenotype compared
      with wild-type controls. In addition, they were protected against diet-induced
      obesity. Here, we show that PRCP(gt/gt) animals have improved metabolic
      parameters compared with wild-type controls under a standard chow diet (SD) as
      well as on a high-fat diet (HFD). Similarly to when they are exposed to SD,
      PRCP(gt/gt) mice exposed to HFD for 13 wk showed a leaner phenotype due to
      decreased fat mass, increased energy expenditure, and locomotor activity. They
      also showed improved insulin sensitivity and glucose tolerance compared with WT
      controls and a significant reduction in fasting glucose levels. These
      improvements occured before changes in body weight and composition were evident,
      suggesting that the beneficial effect of PRCP ablation is independent of the
      adiposity levels. In support of a reduced gluconeogenesis, liver PEPCK and G-6
      Pase mRNA levels were reduced significantly in PRCP(gt/gt) compared with WT mice.
      A significant decrease in liver weight and hepatic triglycerides were also
      observed in PRCP(gt/gt) compared with WT mice. Altogether, our data suggest that
      PRCP is an important regulator of energy and glucose homeostasis since its
      deletion significantly improves metabolic parameters in mice exposed to both SD
      and HFD.

PMID- 22454291
TI  - Glucagon regulates ACC activity in adipocytes through the CAMKKbeta/AMPK pathway.
AB  - Glucagon is important for regulating lipid metabolism in part through its
      inhibition of fatty acid synthesis in adipocytes. Acetyl-CoA carboxylase 1 (ACC1)
      is the rate-limiting enzyme for fatty acid synthesis. Glucagon has been proposed
      to activate cAMP-dependent protein kinase A (PKA), which phosphorylates ACC1 to
      attenuate the lipogenic activity of ACC1. Because AMP-activated protein kinase
      (AMPK) also inhibits fatty acid synthesis by phosphorylation of ACC1, we examined
      the involvement of AMPK and its upstream kinase in the glucagon-elicited
      signaling in adipocytes in vitro and in vivo. LC-MS-MS analysis suggested that
      ACC1 was phosphorylated only at Ser(79), an AMPK-specific site, in glucagon
      treated adipocytes. Pharmacological inhibitors and siRNA knockdown of AMPK or PKA
      in adipocytes demonstrate that glucagon regulates ACC1 and ACC2 activity through
      AMPK but not PKA. By using Ca(2+)/calmodulin-dependent protein kinase kinase-beta
      knockout (CaMKKbeta(-/-)) mice and cultured adipocytes, we further show that
      glucagon activates the CaMKKbeta/AMPK/ACC cascade. Additionally, fasting
      increases the phosphorylation of AMPK and ACC in CaMKKbeta(+/+) but not
      CaMKKbeta(-/-) mice. These results indicate that CaMKKbeta/AMPK signaling is an
      important molecular component in regulating lipid metabolism in adipocytes
      responding to glucagon and could be a therapeutic target for the dysregulation of
      energy storage.

PMID- 22454292
TI  - DEPTOR ubiquitination and destruction by SCF(beta-TrCP).
AB  - beta-Transducin repeats-containing protein (beta-TrCP) is the substrate
      recognition subunit of the SCF (SKP1, CUL1, and F-box protein)-type E3 ubiquitin
      ligase complex. SCF(beta-TrCP) ubiquitinates specifically phosphorylated
      substrates to promote their subsequent destruction by the 26S proteasome and
      plays a critical role in various human diseases including tumorigenesis. We and
      others (Duan S et al. Mol Cell 44: 317-324, 2011; Gao D et al. Mol Cell 44: 290
      303, 2011; Zhao Y et al. Mol Cell 44: 304-316, 2011) recently reported that
      SCF(beta-TrCP) regulates cell growth and autophagy by controlling the
      ubiquitination and destruction of DEPTOR, an endogenous mammalian target of
      rapamycin inhibitor, in a phosphorylation-dependent manner. In this review, we
      discuss beta-TrCP's new downstream substrate, DEPTOR, as well as summarize the
      novel functional aspects of beta-TrCP in controlling cell growth and regulating
      autophagy, in part through governing the stability of DEPTOR.

PMID- 22454294
TI  - Synthesis of nickel(II) azacorroles by Pd-catalyzed amination of alpha,alpha'
      dichlorodipyrrin Ni(II) complex and their properties.
AB  - Synthesis of nickel(II) complexes of meso-aryl-substituted azacorroles was
      performed by Buchwald-Hartwig amination of a dipyrrin Ni(II) complex with
      benzylamine through C-N and C-C coupling. The highly planar structure of Ni(II)
      azacorroles was elucidated by X-ray diffraction analysis. (1)H NMR analysis and
      nucleus independent chemical shift (NICS) calculation on Ni(II) azacorrole
      revealed its distinct aromaticity with [17]triaza-annulene 18pi conjugation. In
      addition, acylation of azacorrole selectively afforded N- and C-acylated
      azacorroles depending on the reaction conditions, showing the dual reactivity of
      azacorroles.

PMID- 22454293
TI  - Adipocyte expression of PU.1 transcription factor causes insulin resistance
      through upregulation of inflammatory cytokine gene expression and ROS production.
AB  - We have reported previously that ETS family transcription factor PU.1 is
      expressed in mature adipocytes of white adipose tissue. PU.1 expression is
      increased greatly in mouse models of genetic or diet-induced obesity. Here, we
      show that PU.1 expression is increased only in visceral but not subcutaneous
      adipose tissues of obese mice, and the adipocytes are responsible for this
      increase in PU.1 expression. To further address PU.1's physiological function in
      mature adipocytes, PU.1 was knocked down in 3T3-L1 cells using retroviral
      mediated expression of PU.1-targeting shRNA. Consistent with previous findings
      that PU.1 regulates its target genes, such as NADPH oxidase subunits and
      proinflammatory cytokines in myeloid cells, the mRNA levels of proinflammatory
      cytokines (TNFalpha, IL-1beta, and IL-6) and cytosolic components of NADPH
      oxidase (p47phox and p40phox) were downregulated significantly in PU.1-silenced
      adipocytes. NADPH oxidase is a main source for reactive oxygen species (ROS)
      generation. Indeed, silencing PU.1 suppressed NADPH oxidase activity and
      attenuated ROS in basal or hydrogen peroxide-treated adipocytes. Silencing PU.1
      in adipocytes suppressed JNK1 activation and IRS-1 phosphorylation at Ser(307).
      Consequently, PU.1 knockdown improved insulin signaling and increased glucose
      uptake in basal and insulin-stimulated conditions. Furthermore, knocking down
      PU.1 suppressed basal lipolysis but activated stimulated lipolysis. Collectively,
      these findings indicate that obesity induces PU.1 expression in adipocytes to
      upregulate the production of ROS and proinflammatory cytokines, both of which
      lead to JNK1 activation, insulin resistance, and dysregulation of lipolysis.
      Therefore, PU.1 might be a mediator for obesity-induced adipose inflammation and
      insulin resistance.

PMID- 22454295
TI  - Glass nanopillar arrays with nanogap-rich silver nanoislands for highly intense
      surface enhanced Raman scattering.
AB  - The enhancement of surface enhanced Raman scattering (SERS) with nanogap-rich
      silver nanoislands surrounding glass nanopillars at wafer level is reported. High
      density hot spots are generated by increasing the number of nanogap-rich
      nanoislands within a detection volume. The SERS substrate shows a high
      enhancement factor of over 10(7)  with excellent signal uniformity (~7.8%) and it
      enables the label-free detection of aqueous DNA base molecules at nanomolar
      level.

PMID- 22454296
TI  - Outcomes of liver transplantation for patients with Alagille syndrome: the
      studies of pediatric liver transplantation experience.
AB  - Alagille syndrome (ALGS) is a multisystem disorder that manifests as childhood
      cholestasis. Reports of liver transplantation (LT) for patients with ALGS have
      come largely from single centers, which have reported survival rates of 57% to
      79%. The aim of this study was to determine LT outcomes for patients with ALGS.
      We performed a retrospective analysis of the Studies of Pediatric Liver
      Transplantation database, which contains information about 3153 pediatric LT
      recipients. Data were available for 91 patients with ALGS and for 236 age-matched
      patients with biliary atresia (BA). The frequency of complex cardiac anomalies
      was lower in the LT group with ALGS versus published ALGS series (5% versus 13%).
      The pretransplant glomerular filtration rate (GFR) was <90 mL/minute/1.73 m(2) in
      18% of the LT patients with ALGS and in 5% of the LT patients with BA (P <
      0.001). The height deficit at listing was worse for the ALGS patients (66%)
      versus the BA patients (22%). The 1-year patient survival rates were 87% for the
      ALGS patients and 96% for the BA patients (P = 0.002). The deaths in the ALGS
      group mostly occurred within the first 30 days. No pretransplant factors
      associated with death were identified in the ALGS group. A survival analysis
      revealed that biliary (P = 0.02), vascular (P < 0.001), central nervous system
      (CNS; P < 0.001), and renal complications (P < 0.001) after LT were associated
      with death in the ALGS group. Renal insufficiency in the ALGS patients worsened
      after LT, and at 1 year, GFR was <90 mL/minute/1.73 m(2) in 22% of the LT
      patients with ALGS but in only 8% of the patients with BA (P = 0.0014). More LT
      pediatric patients with ALGS either were currently receiving special education
      (50% versus 30% for BA patients, P = 0.02) or had received special education in
      the past (60% versus 36%, P = 0.01). Vascular, CNS, and renal complications were
      increased in the ALGS patients after LT, and this reflected multisystem
      involvement. Although the 1-year survival rate was modestly lower for the ALGS
      patients versus the BA patients, the clustering of deaths within the first 30
      days is notable and warrants increased vigilance and further investigation.

PMID- 22454297
TI  - Tissue distribution and metabolism of the putative cancer chemopreventive agent
      3',4',5'-trimethoxyflavonol (TMFol) in mice.
AB  - 3',4',5'-Trimethoxyflavonol (TMFol) is a synthetic flavonol with preclinical
      cancer chemopreventive properties. The hypothesis was tested that, in mice, p.o.
      administration of TMFol results in measureable levels of the parent in target
      tissues. A single oral dose (240 mg/kg) was administered to mice (n = 4 per time
      point) with time points ranging from 5 to 1440 min. TMFol and its metabolites
      were identified and quantitated in all tissues by high-performance liquid
      chromatography (HPLC). Plasma levels of TMFol were at the limit of quantification
      or below, although metabolites were identified. Peak levels of TMFol in the
      gastrointestinal tract and the prostate averaged 1671 +/- 265 ug/g (5.3 umol/g)
      and 6.0 +/- 1.6 ug/g (18.4 nmol/g), and occurred 20 and 360 min post-dose,
      respectively. The area under the tissue concentration-time curve (AUC) for TMFol
      was greater than those of the metabolites, indicating that TMFol is relatively
      metabolically stable. Micromolar TMFol levels are easily achieved in the prostate
      and gastrointestinal tract, suggesting that TMFol might exert chemopreventive
      efficacy at these tissue sites. Further investigations are warranted to elucidate
      the potential chemopreventive potency of TMFol.

PMID- 22454298
TI  - Optimisation of exposure conditions for in vitro radiobiology experiments.
AB  - Despite the long history of using cell cultures in vitro for radiobiological
      studies, there is to date no study specifically addressing the dosimetric
      implications of flask selection and exposure environment in clonogenic assays.
      The consequent variability in dosimetry between laboratories impedes the
      comparison of results. In this study we compare the dose to cells adherent to the
      base of three types of commonly used culture flasks or plates. The cells are
      exposed to a 6MV clinical photon beam using either an open or a half blocked
      field. The depth of medium in each flask is varied with the medium surrounding
      the flask either water or air. The results show that the dose to the cells is
      more affected by the scattering conditions surrounding the flasks than by the
      level of filling within the flask. It is recommended that water or a water
      equivalent phantom material is used to surround the flasks or plates to
      approximate full scatter conditions at the cell layer. However for modulated
      fields, surrounding the 24 well plates with water-equivalent material is
      inadequate because of the large volume of air surrounding individual wells. Our
      results stress the importance of measuring the dose for new experimental
      configurations.

PMID- 22454300
TI  - Workers who stay at work despite chronic nonspecific musculoskeletal pain: do
      they differ from workers with sick leave?
AB  - PURPOSE: Most workers with chronic nonspecific musculoskeletal pain (CMP) do not
      take sick leave, nor consult a health care professional or search vocational
      rehabilitation. Yet, the knowledge of many researchers, clinicians and policy
      makers is largely based on people with CMP who discontinue work. The aim of this
      study was to explore characteristics of workers who stay at work despite CMP, and
      to compare these with sick-listed workers with CMP following vocational
      rehabilitation. METHODS: The clinical characteristics of workers who stay at work
      despite CMP (n = 119) and sick-listed workers who follow vocational
      rehabilitation (n = 122) were described and the differences between these groups
      were assessed. Logistic regression analysis was used to assess differences
      between the groups and to determine which variables predicted group status.
      RESULTS: Workers who stayed at work despite CMP reported significantly lower
      levels of fear avoidance (OR = 0.94), pain catastrophizing (OR = 0.93), perceived
      workload (OR = 0.93), and higher pain acceptance (OR = 1.11), life control (OR =
      1.62) and pain self-efficacy (OR = 1.09) compared to sick-listed workers
      following rehabilitation, even after controlling for confounders. The groups did
      not differ on physical activity level, active coping and work satisfaction. Group
      status was predicted best by pain intensity, duration of pain, pain acceptance,
      perceived workload, mental health, and psychological distress (area under the
      receiver operating characteristic curve = 0.91, 95% CI = 0.87-0.95). CONCLUSIONS:
      A wide range of characteristics of workers who stay at work despite CMP were
      explored. Relevant differences from sick-listed workers with CMP were observed in
      all domains of the bio-psycho-social model. Six main predictors were identified
      that best discriminate between both groups.

PMID- 22454302
TI  - Electrophilicities of bissulfonyl ethylenes.
AB  - Kinetics of the reactions of bissulfonyl ethylenes with various carbanions, a
      sulfur ylide, and siloxyalkenes have been investigated photometrically at 20 
      degrees C. The second-order rate constants have been combined with the known
      nucleophile- specific parameters N and s(N) for the nucleophiles to calculate the
      empirical electrophilicity parameters E of bissulfonyl ethylenes according to the
      linear free energy relationship log k(20  degrees C)=s(N)(N+E). Structure
      reactivity relationships are discussed, and it is shown that the electrophilicity
      parameters E derived in this work can be employed to define the synthetic
      potential of bissulfonyl ethylenes as Michael acceptors.

PMID- 22454301
TI  - Directional photofluidization lithography: micro/nanostructural evolution by
      photofluidic motions of azobenzene materials.
AB  - This review demonstrates directional photofluidization lithography (DPL), which
      makes it possible to fabricate a generic and sophisticated micro/nanoarchitecture
      that would be difficult or impossible to attain with other methods. In
      particular, DPL differs from many of the existing micro/nanofabrication methods
      in that the post-treatment (i.e., photofluidization), after the preliminary
      fabrication process of the original micro/nanostructures, plays a pivotal role in
      the various micro/nanostructural evolutions including the deterministic reshaping
      of architectures, the reduction of structural roughness, and the dramatic
      enhancement of pattern resolution. Also, DPL techniques are directly compatible
      with a parallel and scalable micro/nanofabrication. Thus, DPL with such
      extraordinary advantages in micro/nanofabrication could provide compelling
      opportunities for basic micro/nanoscale science as well as for general technology
      applications.

PMID- 22454303
TI  - Fabrication of chitosan/hydroxylapatite composite rods with a layer-by-layer
      structure for fracture fixation.
AB  - A composite rod for fracture fixation using chitosan (CHI)/hydroxylapatite (HA)
      was prepared by means of in situ precipitation, which had a layer-by-layer
      structure, good mechanical properties, and cell compatibilities. The CHI/HA
      composite rods were precipitated from the chitosan solution with calcium and
      phosphorus precursors, followed by treatment with a tripolyphosphate-trisodium
      phosphate solution (pH >13) to crosslink the CHI and to hydrolyze the calcium
      phosphates to nanocrystalline HA. The results of FTIR, XRD, and TEM measurements
      confirmed that HA had been formed within the CHI matrix. The effects of the
      CHI/HA ratios (20/0, 20/1, 20/2, 20/4, and 20/5, w/w) on the mechanical
      properties were investigated. At the CHI/HA ratio of 20/4 (w/w), the bending
      strength and modulus of the rods were 133 MPa and 6.8 GPa, respectively. Pre
      osteoblast MC3T3-E1 cells were cultured in an extract of the CHI/HA rods (20/4,
      w/w) to study the cell compatibilities of the composite. The observations
      indicated that the CHI/HA composite could promote the growth of MC3T3-E1 cells
      better than the composite without HA (p < 0.05). Furthermore, the co-cultivation
      of the cells and the CHI/HA composite showed that cells fully spread on the
      surface of the composite with an obvious cytoskeleton organization, which also
      revealed that the CHI/HA composite had a good biocompatibility.

PMID- 22454304
TI  - Alcohol-related injuries and alcohol control policy in Lithuania: effect of the
      year of sobriety, 2008.
AB  - AIMS: To evaluate the changes in mortality and the years of potential life lost
      (YPLL) due to alcohol-related injuries, as well as the impact of alcohol-related
      injuries on life expectancy during the period of the implementation of
      comprehensive alcohol control policy in Lithuania. METHODS: Data on deaths from
      injuries (ICD-10 codes V01-Y98) of the able-bodied population (aged 15-64 years)
      during 2006-2009 were obtained from the Lithuanian Department of Statistics. Age
      standardized rates of alcohol-related mortality and YPLL per 100, 000 population
      due to injuries and the impact of alcohol-related injuries on life expectancy
      were calculated. The results of forensic autopsies were the basis for the alcohol
      attributable fraction. RESULTS: The age-standardized YPLL/100,000 of the able
      bodied population due to alcohol-related injuries was 2285.6 (4067.5 for males
      and 573.6 for females) in 2009. In 2009, YPLL/100,000 due to alcohol-related
      injuries declined by 16.3%, while due to alcohol-related traffic accidents by
      51.2% when compared with 2006. However, YPLL/100, 000 due to alcohol-related
      suicides increased among males. A 15 to 64-year-old decedent lost an average of
      21.2 years of life due to alcohol-related injuries (21.6 years on average per
      male and 19.1 per female). The impact of alcohol-related injuries on life
      expectancy decreased from 1.14 years (1.86 for males and 0.34 for females) in
      2006 to 0.97 years (1.62 for males and 0.26 for females) in 2009. CONCLUSION: The
      positive changes in YPLL due to alcohol-related injuries and the impact of
      alcohol-related injuries on life expectancy indicate successful implementation of
      evidence-based alcohol control measures.

PMID- 22454305
TI  - [Takotsubo cardiomyopathy - an important differential diagnosis in acute chest
      pain].

PMID- 22454307
TI  - [Consensus recommendations for the assessment of fitness to drive in cognitively
      impaired patients].
AB  - Memory Clinics provide evidence based diagnosis and treatment of dementia.
      Whenever a diagnosis of dementia is made, it is important to inform the patients
      about the possible impact of dementia on driving. Patients and their next of kin
      require competent advice whenever this difficult question is addressed and the
      mobility desire and the risks related to driving need to be carefully weight up.
      The time of diagnosis does not necessarily equate to the time when a person with
      dementia becomes an unsafe driver. The cause and severity of dementia,
      comorbidities and the current medication need to be carefully taken into account
      for this decision. On behalf of the association of the Swiss Memory Clinics, a
      group of experts has developed recommendations to assess fitness to drive in
      cognitively impaired older adults.

PMID- 22454308
TI  - [Screening for thrombophilia 2011: who are the candidates?].
AB  - Heritable thrombophilia as a concept in hemostasis has been continuously
      discovered parallel to the knowledge on physiology of bleeding disorders. Since
      the 1980s it has become increasingly popular to search for thrombophilia in
      patients with thromboembolism and their relatives. Although initially no direct
      evidence existed for any advantage for the patients, successive clinical studies
      have helped to understand the risk of thrombosis and to stratify the patients in
      relation to the thrombophilic defect. In the meantime national and international
      guidelines have been published, suggesting which candidates should be examined
      and what tests should be performed. In the present paper we summarise and explain
      the rationale of these guidelines from the european point of view.

PMID- 22454309
TI  - [Assessment and referral after emergency treatment in suspected anaphylactic
      reaction: summary of the NICE guideline].

PMID- 22454310
TI  - [Numbness in the hands].
AB  - My hands are numb is a common complaint in primary care. Generally, carpal tunnel
      syndrome can be suspected. This case report explains typical aspects of clinical
      reasoning used by neurologists to confirm the diagnosis, and also provides some
      details of "red flags" based on history and examination. Additionally, a short
      introduction to electrodiagnostic procederes is included and illustrated with
      diagrams.

PMID- 22454311
TI  - [Persistent Eosinophilia--differential diagnosis and work-up].
AB  - The differential diagnosis of eosinophilia is broad and constitutes a major
      challenge for both, the general practitioner and the hematologist. Whereas in
      developing countries secondary eosinophilia is commonly caused by parasitic
      infections, in Western and European countries eosinophilia is more often
      associated with atopic diseases or drug-related. This case-report presents an
      asymptomatic patient with marked persisting eosinophilia caused by
      Strongyloidiasis in whom parasitic stool examinations were repeatedly negative
      and infection could only be established by serologic testing.

PMID- 22454312
TI  - [Not Available].

PMID- 22454313
TI  - [Not Available].

PMID- 22454318
TI  - Next-generation sequencing for minimal residual disease monitoring in acute
      myeloid leukemia patients with FLT3-ITD or NPM1 mutations.
AB  - Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia
      (AML) patients has been hampered by lack of a reliable, uniform MRD marker
      applicable to all patients. We evaluated next-generation sequencing (NGS) for MRD
      assessment in AML patients (n = 80 samples). The ability of NGS technologies to
      generate thousands of clonal sequences makes it possible to determine the allelic
      ratio of sequence variants. Using NGS, we were able to determine the allelic
      ratio of different FLT3-internal tandem duplication (ITD) clones within one
      patient sample, in addition to resolution of FLT3-ITD insertion site, length, and
      sequence in a single analysis. Furthermore, NGS allowed us to study emergence of
      clonal dominance. Parallel assessment of MRD by NGS and quantitative real-time
      polymerase chain reaction in NPM1 mutated patients was concordant in 95% of
      analyzed samples (n = 38). The frequency of mutated alleles was linearly
      quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage,
      it reflects a highly flexible and reliable tool to assess MRD in leukemia
      patients.

PMID- 22454319
TI  - Superior electrochemical performance of sulfur/graphene nanocomposite material
      for high-capacity lithium-sulfur batteries.
AB  - Sulfur/graphene nanocomposite material has been prepared by incorporating sulfur
      into the graphene frameworks through a melting process. Field-emission scanning
      electron microscope analysis shows a homogeneous distribution of sulfur in the
      graphene nanosheet matrix. The sulfur/graphene nanocomposite exhibits a super
      high lithium-storage capacity of 1580 mA h g(-1) and a satisfactory cycling
      performance in lithium-sulfur cells. The enhancement of the reversible capacity
      and cycle life could be attributed to the flexible graphene nanosheet matrix,
      which acts as a conducting medium and a physical buffer to cushion the volume
      change of sulfur during the lithiation and delithiation process. Graphene-based
      nanocomposites can significantly improve the electrochemical performance of
      lithium-sulfur batteries.

PMID- 22454320
TI  - LC-MS/MS method for simultaneous analysis of uracil, 5,6-dihydrouracil, 5
      fluorouracil and 5-fluoro-5,6-dihydrouracil in human plasma for therapeutic drug
      monitoring and toxicity prediction in cancer patients.
AB  - The chemotherapeutic drug 5-fluorouracil (5-FU) is widely used for treating solid
      tumors. Response to 5-FU treatment is variable with 10-30% of patients
      experiencing serious toxicity partly explained by reduced activity of
      dihydropyrimidine dehydrogenase (DPD). DPD converts endogenous uracil (U) into
      5,6-dihydrouracil (UH(2) ), and analogously, 5-FU into 5-fluoro-5,6-dihydrouracil
      (5-FUH(2) ). Combined quantification of U and UH(2) with 5-FU and 5-FUH(2) may
      provide a pre-therapeutic assessment of DPD activity and further guide drug
      dosing during therapy. Here, we report the development of a liquid chromatography
      tandem mass spectrometry assay for simultaneous quantification of U, UH(2) , 5-FU
      and 5-FUH(2) in human plasma. Samples were prepared by liquid-liquid extraction
      with 10:1 ethyl acetate-2-propanol (v/v). The evaporated samples were
      reconstituted in 0.1% formic acid and 10 MUL aliquots were injected into the HPLC
      system. Analyte separation was achieved on an Atlantis dC(18) column with a
      mobile phase consisting of 1.0 mm ammonium acetate, 0.5 mm formic acid and 3.3%
      methanol. Positively ionized analytes were detected by multiple reaction
      monitoring. The analytical response was linear in the range 0.01-10 MUm for U,
      0.1-10 MUm for UH(2) , 0.1-75 MUm for 5-FU and 0.75-75 MUm for 5-FUH(2) ,
      covering the expected concentration ranges in plasma. The method was validated
      following the FDA guidelines and applied to clinical samples obtained from ten 5
      FU-treated colorectal cancer patients. The present method merges the analysis of
      5-FU pharmacokinetics and DPD activity into a single assay representing a
      valuable tool to improve the efficacy and safety of 5-FU-based chemotherapy.

PMID- 22454321
TI  - Observation of lasing emission from carbon nanodots in organic solvents.
AB  - Lasing is observed from carbon nanodots (C-dots) dispersed into a layer of
      poly(ethylene glycol) coated on the surface of optical fibers under 266 nm
      optical excitation. This is due to the enhancement of photoluminescence intensity
      via the esterification of carboxylic groups of the C-dots, and the formation of
      high-Q cylindrical microcavities to support second-type whispering gallery modes.

PMID- 22454322
TI  - Wear of ceramic-on-carbon fiber-reinforced poly-ether ether ketone hip
      replacements.
AB  - Total hip replacement has been a successful surgical intervention for over 50
      years, with the majority of bearings using a polyethylene cup. Long-term failure
      due to osteolysis and loosening has been widely documented and alternative
      bearings have been sought. A novel carbon fiber-reinforced poly-ether ether
      ketone (CFR-PEEK) cup was investigated through experimental friction and wear
      studies. Friction studies demonstrated the bearings operated in a boundary
      lubrication condition, with friction factors higher than those for other hip
      replacement bearings. The wear study was conducted with 36 mm diameter bearings
      tested against Biolox Delta heads for a period of 10 million cycles. The mean
      volumetric wear rate was 0.3 mm(3)/Mc, indicating the ceramic-on-CFR-PEEK bearing
      to be a very low wearing option for total hip replacement.

PMID- 22454323
TI  - Octanoic acid suppresses harmaline-induced tremor in mouse model of essential
      tremor.
AB  - Recent work exploring the use of high-molecular weight alcohols to treat
      essential tremor (ET) has identified octanoic acid as a potential novel tremor
      suppressing agent. We used an established harmaline-based mouse model of ET to
      compare tremor suppression by 1-octanol and octanoic acid. The dose-related
      effect on digitized motion power within the tremor bandwidth as a fraction of
      overall motion power was analyzed. Both 1-octanol and octanoic acid provided
      significant reductions in harmaline tremor. An 8-carbon alkyl alcohol and
      carboxylic acid each suppress tremor in a pre-clinical mouse model of ET. Further
      studies are warranted to determine the safety and efficacy of such agents in
      humans with ET.

PMID- 22454325
TI  - Beta-blockers in patients with refractory ascites: to treat or not to treat. That
      is the question. but, what is the answer?

PMID- 22454324
TI  - Identification of osteosarcoma driver genes by integrative analysis of copy
      number and gene expression data.
AB  - High-grade osteosarcoma is a tumor with a complex genomic profile, occurring
      primarily in adolescents with a second peak at middle age. The extensive genomic
      alterations obscure the identification of genes driving tumorigenesis during
      osteosarcoma development. To identify such driver genes, we integrated DNA copy
      number profiles (Affymetrix SNP 6.0) of 32 diagnostic biopsies with 84 expression
      profiles (Illumina Human-6 v2.0) of high-grade osteosarcoma as compared with its
      putative progenitor cells, i.e., mesenchymal stem cells (n = 12) or osteoblasts
      (n = 3). In addition, we performed paired analyses between copy number and
      expression profiles of a subset of 29 patients for which both DNA and mRNA
      profiles were available. Integrative analyses were performed in Nexus Copy Number
      software and statistical language R. Paired analyses were performed on all probes
      detecting significantly differentially expressed genes in corresponding LIMMA
      analyses. For both nonpaired and paired analyses, copy number aberration
      frequency was set to >35%. Nonpaired and paired integrative analyses resulted in
      45 and 101 genes, respectively, which were present in both analyses using
      different control sets. Paired analyses detected >90% of all genes found with the
      corresponding nonpaired analyses. Remarkably, approximately twice as many genes
      as found in the corresponding nonpaired analyses were detected. Affected genes
      were intersected with differentially expressed genes in osteosarcoma cell lines,
      resulting in 31 new osteosarcoma driver genes. Cell division related genes, such
      as MCM4 and LATS2, were overrepresented and genomic instability was predictive
      for metastasis-free survival, suggesting that deregulation of the cell cycle is a
      driver of osteosarcomagenesis.

PMID- 22454326
TI  - Phase- and size-controllable synthesis of hexagonal upconversion rare-earth
      fluoride nanocrystals through an oleic acid/ionic liquid two-phase system.
AB  - Herein, we introduce a facile, user- and environmentally friendly (n-octanol
      induced) oleic acid (OA)/ionic liquid (IL) two-phase system for the phase- and
      size-controllable synthesis of water-soluble hexagonal rare earth (RE = La, Gd,
      and Y) fluoride nanocrystals with uniform morphologies (mainly spheres and
      elongated particles) and small sizes (<50 nm). The unique role of the IL 1-butyl
      3-methylimidazolium hexafluorophosphate (BmimPF(6)) and n-octanol in modulating
      the phase structure and particle size are discussed in detail. More importantly,
      the mechanism of the (n-octanol-induced) OA/IL two-phase system, the formation of
      the RE fluoride nanocrystals, and the distinctive size- and morphology
      controlling capacity of the system are presented. BmimPF(6) is versatile in term
      of crystal-phase manipulation, size and shape maintenance, and providing water
      solubility in a one-step reaction. The luminescent properties of Er(3+)-, Ho(3+)
      , and Tm(3+)-doped LaF(3), NaGdF(4), and NaYF(4) nanocrystals were also studied.
      It is worth noting that the as-prepared products can be directly dispersed in
      water due to the hydrophilic property of Bmim(+) (cationic part of the IL) as a
      capping agent. This advantageous feature has made the IL-capped products
      favorable in facile surface modifications, such as the classic Stober method.
      Finally, the cytotoxicity evaluation of NaYF(4):Yb,Er nanocrystals before and
      after silica coating was conducted for further biological applications.

PMID- 22454327
TI  - Biocompatibility of polymethylmethacrylate resins used in dentistry.
AB  - Biocompatibility or tissue compatibility describes the ability of a material to
      perform with an appropriate host response when applied as intended. Poly
      methylmethacrylate (PMMA) based resins are most widely used resins in dentistry,
      especially in fabrication of dentures and orthodontic appliances. They are
      considered cytotoxic on account of leaching of various potential toxic
      substances, most common being residual monomer. Various in vitro and in vivo
      experiments and cell based studies conducted on acrylic based resins or their
      leached components have shown them to have cytotoxic effects. They can cause
      mucosal irritation and tissue sensitization. These studies are not only important
      to evaluate the long term clinical effect of these materials, but also help in
      further development of alternate resins. This article reviews information from
      scientific full articles, reviews, or abstracts published in dental literature,
      associated with biocompatibility of PMMA resins and it is leached out components.
      Published materials were searched in dental literature using general and
      specialist databases, like the PubMED database.

PMID- 22454329
TI  - Sodium 1-naphthalenesulfonate-functionalized reduced graphene oxide stabilizes
      silver nanoparticles with lower cytotoxicity and long-term antibacterial
      activity.
AB  - Silver nanoparticles (AgNPs) are increasingly used in daily life for their
      antibacterial properties, but their low stability and high cytotoxicity hamper
      practical applications. In this work, sodium 1-naphthalenesulfonate
      functionalized reduced graphene oxide (NA-rGO) was used as a substrate for AgNPs
      to produce a AgNP-NA-rGO hybrid. This hybrid showed substantially higher
      antibacterial activity than polyvinyl pyrrolidone (PVP)-stabilized AgNPs, and the
      AgNPs on NA-rGO were more stable than the AgNPs on PVP, resulting in long-term
      antibacterial effects. More importantly, this hybrid showed excellent water
      solubility and low cytotoxicity, suggesting the great potential application as
      sprayable reduced graphene oxide based antibacterial solutions.

PMID- 22454330
TI  - Photomagnetism of a sym-cis-dithiocyanato iron(II) complex with a tetradentate
      N,N'-bis(2-pyridylmethyl)1,2-ethanediamine ligand.
AB  - A comprehensive study of the magnetic and photomagnetic behaviors of cis
      [Fe(picen)(NCS)(2) ] (picen = N,N'-bis(2-pyridylmethyl)1,2-ethanediamine) was
      carried out. The spin-equilibration was extremely slow in the vicinity of the
      thermal spin-transition. When the cooling speed was slower than 0.1 K  min(-1),
      this complex was characterized by an abrupt thermal spin-transition at about 70
      K. Measurement of the kinetics in the range 60-70 K was performed to approach the
      quasi-static hysteresis loop. At low temperatures, the metastable HS state was
      quenched by a rapid freezing process and the critical T(TIESST) temperature,
      which was associated with the thermally induced excited spin-state-trapping
      (TIESST) effect, was measured. At 10 K, this complex also exhibited the well
      known light-induced excited spin-state-trapping (LIESST) effect and the T(LIESST)
      temperature was determined. The kinetics of the metastable HS states, which were
      generated from the freezing effect and from the light-induced excitation, was
      studied. Single-crystal X-ray diffraction as a function of speed-cooling and
      light conditions at 30 K revealed the mechanism of the spin-crossover in this
      complex as well as some direct relationships between its structural properties
      and its spin state. This spin-crossover (SCO) material represents a fascinating
      example in which the metastability of the HS state is in close vicinity to the
      thermal spin-transition region. Moreover, it is a beautiful example of a complex
      in which the metastable HS states can be generated, and then compared, either by
      the freezing effect or by the LIESST effect.

PMID- 22454328
TI  - Forgetting in context: the effects of age, emotion, and social factors on
      retrieval-induced forgetting.
AB  - Retrieval-induced forgetting (RIF) refers to the finding that selectively
      retrieving some information impairs subsequent memory for related but
      nonretrieved information. This occurs both for the individual doing the
      remembering (i.e., within-individual retrieval-induced forgetting: WI-RIF), as
      well as for individuals merely listening to those recollections (i.e., socially
      shared retrieval-induced forgetting: SS-RIF). In the present study, we examined
      how the contextual factors of age and emotion independently and interactively
      affect both WI-RIF and SS-RIF. The results indicated that both WI-RIF and SS-RIF
      occurred at equivalent levels, both for younger and older adults and for neutral
      and emotional information. However, we identified a boundary condition to this
      effect: People only exhibited SS-RIF when the speaker that they were listening to
      was of the same sex as themselves. Given that participants reported feeling
      closer to same-sex speakers, this suggests that people co-retrieve more, and
      therefore exhibit increased SS-RIF, with close others. In everyday life, these
      RIF effects should influence what information is remembered versus forgotten in
      individual and collective memories.

PMID- 22454331
TI  - Hepatitis B surface antigen quantification: not what it seems on the surface.

PMID- 22454332
TI  - Approach and avoidance movements are unaffected by cognitive conflict: a
      comparison of the Simon effect and stimulus-response compatibility.
AB  - Participants in this study reached from central fixation to a lateral position
      that either contained or was opposite to the stimulus. Cognitive conflict was
      induced when the stimulus and response directions did not correspond. In the
      Simon task, the response direction was cued by the color of the lateral stimulus,
      and corresponding and noncorresponding trials varied randomly in the same block
      of trials, resulting in high uncertainty and long reaction times (RTs). In the
      stimulus-response compatibility (SRC) task, participants reached toward or away
      from the stimulus in separate blocks of trials, resulting in low uncertainty and
      short RTs. In the SRC task, cognitive conflict in noncorresponding trials slowed
      down RTs but hardly affected reach trajectories. In the Simon task, both RTs and
      reach trajectories were strongly influenced by stimulus-response correspondence.
      Despite the overall longer RTs in the Simon task, reaches were less direct and
      deviated toward the stimulus in noncorresponding trials. Thus, cognitive conflict
      was resolved before movement initiation in the SRC task, whereas it leaked into
      movement execution in the Simon task. Current theories of the Simon effect, such
      as the gating of response activation or response code decay, are inconsistent
      with our results. We propose that the SRC task was decomposed as approaching and
      avoiding the stimulus, which is sustained by stereotyped visuomotor routines.
      With complex stimulus-response relationships (Simon task), responses had to be
      coded as leftward and rightward, with more uncertainty about how to execute the
      action. This uncertainty permitted cognitive conflict to leak into the movement
      execution.

PMID- 22454333
TI  - Effect of crystallization heat treatment on the microstructure of niobium-doped
      fluorapatite glass-ceramics.
AB  - Our goal was to study the effect of heat treatment temperature and heating rate
      on the microstructure and crystalline phases and assess the domain of existence
      of submicrometer fluorapatite crystals in niobium-doped fluorapatite glass
      ceramics for biomedical applications. Glass-ceramic specimens were prepared by
      casting and heat treatment between 700 and 1200 degrees C using a fast or a slow
      heating rate. The microstructure was characterized by atomic force microscopy and
      scanning electron microscopy. Crystalline phases were analyzed by x-ray
      diffraction. AFM of the as-cast glass revealed that amorphous phase separation
      occurred in this system. XRD confirmed the presence of fluorapatite in all
      specimens, together with forsterite and enstatite at higher temperatures. Both
      heating rate and heat treatment temperature strongly influenced microstructure
      and crystallinity. A dual microstructure with submicrometer fluorapatite crystals
      and polygonal forsterite crystals was obtained when slow heating rates and
      crystallization temperatures between 950 and 1100 degrees C were used. Needle
      shaped fluorapatite crystals appeared after heat treatment above 1100 degrees C.
      Fast heating rates led to an increase in crystal size. Heat treatment
      temperatures should remain below 1100 degrees C, together with slow heating
      rates, to prevent crystal dissolution, and preserve a dual microstructure of
      finely dispersed submicrometer crystals without growth of needle-shaped crystals.

PMID- 22454334
TI  - N-heterocyclic carbene-catalyzed aerobic oxidative direct esterification of
      aldehydes with organoboronic acids.

PMID- 22454335
TI  - Strategic use of non-native diselenide bridges to steer oxidative protein
      folding.

PMID- 22454336
TI  - Cost-effectiveness of boceprevir or telaprevir for untreated patients with
      genotype 1 chronic hepatitis C.
AB  - Randomized controlled trials (RCTs) show that triple therapy (TT) with
      peginterferon alpha, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more
      effective than peginterferon-ribavirin dual therapy (DT) in the treatment of
      previously untreated patients with genotype 1 (G(1) ) chronic hepatitis C (CHC).
      We assessed the cost-effectiveness of TT compared to DT in the treatment of
      untreated patients with G(1) CHC. We created a Markov Decision Model to evaluate,
      in untreated Caucasian patients age 50 years, weight 70 kg, with G(1) CHC and
      Metavir F2 liver fibrosis score, for a time horizon of 20 years, the cost
      effectiveness of the following five competing strategies: 1) boceprevir response
      guided therapy (BOC-RGT); 2) boceprevir IL28B genotype-guided strategy (BOC
      IL28B); 3) boceprevir rapid virologic response (RVR)-guided strategy (BOC-RVR);
      4) telaprevir response-guided therapy (TVR-RGT); 5) telaprevir IL28B genotype
      guided strategy (TVR-IL28B). Outcomes included life-years gained (LYG), costs (in
      2011 euros) and incremental cost-effectiveness ratio (ICER). In the base-case
      analysis BOC-RVR and TVR-IL28B strategies were the most effective and cost
      effective of evaluated strategies. LYG was 4.04 with BOC-RVR and 4.42 with TVR
      IL28B. ICER compared with DT was ? 8.304 per LYG for BOC-RVR and ? 11.455 per LYG
      for TVR-IL28B. The model was highly sensitive to IL28B CC genotype, likelihood of
      RVR and sustained virologic response, and BOC/TVR prices. CONCLUSION: In
      untreated G(1) CHC patients age 50 years, TT with first-generation protease
      inhibitors is cost-effective compared with DT. Multiple strategies to reduce
      costs and improve effectiveness include RVR or genotype-guided treatment.

PMID- 22454337
TI  - Hydrodynamic shear-stress-dependent retention of endothelial and endothelial
      progenitor cells adhered to vascular endothelial growth factor-fixed surfaces.
AB  - The luminal surfaces of small-diameter artificial vascular grafts must be fully
      endothelialized to be nonthrombogenic following implantation. To achieve this
      goal, we have attempted to capture circulating endothelial progenitor cells
      (EPCs) in situ on the luminal surfaces of implanted grafts. We examined potential
      receptor-ligand pairs that promote selective and tight adhesion of EPCs using a
      radial flow chamber comprising three regions, each containing a specific protein
      bound substrate: fibronectin (FN) for integrin, and vascular endothelial growth
      factor (VEGF) and anti-Flk-1 antibody for VEGF receptor. In the presence of shear
      stress, the greatest retention of endothelial cells and EPCs was observed with FN
      followed by VEGF and then anti-Flk-1 antibody. Regardless of the bound protein,
      cell adhesion increased with larger areas of cell adhesion and enhanced cell
      spreading; the latter was also greatest with FN followed by VEGF and then anti
      Flk-1 antibody. The distribution of vinculin-a key protein in focal adhesion
      plaques-in adherent endothelial cells was examined using total internal
      reflection fluorescence microscopy; FN-bound surfaces resulted in larger areas of
      adhesion and more focal adhesion plaques compared with surfaces bound with VEGF.
      On the other hand, examining these parameters relative to the area of cell
      adhesion revealed that VEGF-bound surfaces resulted in larger focal adhesion
      areas and greater fluorescence signals, both of which indicate increased
      resistance to shear stress. We also discuss in situ capturing of EPCs on surfaces
      bound with VEGF or anti-Flk-1 antibody, with the goal of creating endothelialized
      small-diameter vascular grafts.

PMID- 22454338
TI  - Breastfeeding and transmission of HIV-1: epidemiology and global magnitude.

PMID- 22454339
TI  - Breastfeeding and transmission of viruses other than HIV-1.

PMID- 22454340
TI  - Breastfeeding among HIV-1 infected women: maternal health outcomes and social
      repercussions.

PMID- 22454341
TI  - Early diagnosis of HIV infection in the breastfed infant.

PMID- 22454342
TI  - Virologic determinants of breast milk transmission of HIV-1.

PMID- 22454344
TI  - Animal models of HIV transmission through breastfeeding and pediatric HIV
      infection.

PMID- 22454343
TI  - HIV-1 resistance to antiretroviral agents: relevance to mothers and infants in
      the breastfeeding setting.

PMID- 22454345
TI  - Antiretroviral pharmacology in breast milk.

PMID- 22454346
TI  - The immune system of breast milk: antimicrobial and anti-inflammatory properties.

PMID- 22454347
TI  - B lymphocyte-derived humoral immune defenses in breast milk transmission of the
      HIV-1.

PMID- 22454348
TI  - Cellular immunity in breast milk: implications for postnatal transmission of HIV
      1 to the infant.

PMID- 22454349
TI  - Antiretroviral drugs during breastfeeding for the prevention of postnatal
      transmission of HIV-1.

PMID- 22454351
TI  - Non-antiretroviral approaches to prevention of breast milk transmission of HIV-1:
      exclusive breastfeeding, early weaning, treatment of expressed breast milk.

PMID- 22454352
TI  - Breast milk micronutrients and mother-to-child transmission of HIV-1.

PMID- 22454350
TI  - Immune approaches for the prevention of breast milk transmission of HIV-1.

PMID- 22454353
TI  - Historical perspective of african-based research on HIV-1 transmission through
      breastfeeding: the Malawi experience.

PMID- 22454354
TI  - Breastfeeding and HIV infection in China.

PMID- 22454355
TI  - The role of the President's Emergency Plan for AIDS Relief in infant and young
      child feeding guideline development and program implementation.

PMID- 22454356
TI  - HIV-1 and breastfeeding in the United States.

PMID- 22454357
TI  - Pendulum swings in HIV-1 and infant feeding policies: now halfway back.

PMID- 22454358
TI  - Should women with HIV-1 infection breastfeed their infants? It depends on the
      setting.

PMID- 22454359
TI  - The future of breastfeeding in the face of HIV-1 infection: science and policy.

PMID- 22454360
TI  - Quadruple click: a facile pathway leading to tetrakis(4-(1,2,3-triazolyl)methyl)
      ethylenediamine derivatives as a new class of extracting agents for soft metal
      ions.
AB  - Tetrakis(triazolylmethyl)ethylenediamine, which is a class of tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN) analogue, is synthesized by a quadruple
      click reaction of tetrapropargylated ethylenediamine and four equivalents of
      alkyl azide. The obtained compound efficiently extracted the soft metal
      cadmium(II) ions by solvent extraction. It is also found that an N-isopropylacryl
      amide (NIPA) gel using the triazole ethylenediamine as a cross-linker exhibits a
      temperature-dependent extraction performance.

PMID- 22454361
TI  - Controlled construction of metal-organic frameworks: hydrothermal synthesis, X
      ray structure, and heterogeneous catalytic study.
AB  - The role of pH in the formation of metal-organic frameworks (MOFs) has been
      studied for a series of magnesium-based carboxylate framework systems. Our
      investigations have revealed the formation of five different zero-dimensional
      (0D) to three-dimensional (3D) ordered frameworks from the same reaction mixture,
      merely by varying the pH of the medium. The compounds were synthesized by the
      hydrothermal method and characterized by single-crystal X-ray diffraction.
      Increase of the pH of the medium led to abstraction of the imine hydrogen from
      the ligand and a concomitant increase in the OH(-) ion concentration in the
      solution, facilitating the construction of higher dimensional framework
      compounds. A stepwise increase in pH resulted in a stepwise increase in the
      dimensionality of the network, ultimately leading to the formation of a 3D porous
      solid. A gas adsorption study of the 3D framework compound confirmed its
      microporosity with a BET surface area of approximately 450 m(2)  g(-1). Notably,
      the 3D framework compound catalyzes aldol condensation reactions of various
      aromatic aldehydes with acetone under heterogeneous conditions.

PMID- 22454362
TI  - Reagentless oxidative folding of disulfide-rich peptides catalyzed by an
      intramolecular diselenide.

PMID- 22454363
TI  - Low-density lipoprotein receptor-related protein 1 mediates hypoxia-induced very
      low density lipoprotein-cholesteryl ester uptake and accumulation in
      cardiomyocytes.
AB  - AIMS: The myocardium accumulates intracellular lipids under ischaemic conditions,
      and myocardial fat deposition is closely associated with cardiac dysfunction. Our
      aims were to analyse the effect of hypoxia on low-density lipoprotein receptor
      related protein 1 (LRP1) expression in neonatal rat ventricular myocytes (NRVM)
      and cardiac-derived HL-1 cells and the molecular mechanisms involved in this
      effect, to determine the role of LRP1 in the very low density lipoprotein (VLDL)
      uptake by hypoxic cardiomyocytes, and to study the effect of hypoxia on
      lipoprotein receptor expression and myocardial lipid profile in an in vivo
      porcine experimental model of acute myocardial infarction. METHODS AND RESULTS:
      Thin-layer chromatography after lipid extraction showed that VLDL exposure leads
      to cholesteryl ester (CE) and triglyceride (TG) accumulation in a dose-dependent
      manner and that hypoxic conditions further increased VLDL-derived intracellular
      lipid accumulation in HL-1 cells. Knockdown of LRP1 through lentiviral-mediated
      interfering RNA specifically prevented hypoxia-induced VLDL-CE internalization in
      HL-1 cells and NRVM. Lipopolysaccharide (LPS)-induced LRP1 overexpression
      specifically increased VLDL-CE accumulation in NRVM. In addition, using double
      radiolabelled [(3)H]CE-[(14)C]TG-VLDL, we found that LRP1 deficiency specifically
      prevented hypoxia-induced VLDL-[(3)H]CE uptake. Finally, in an in vivo porcine
      model of infarcted myocardium, ischaemic areas exhibited LRP1 protein up
      regulation and intramyocardial CE overaccumulation. CONCLUSION: Our results
      demonstrate that hypoxia increases LRP1 expression through HIF-1alpha and that
      LRP1 overexpression mediates hypoxia-induced VLDL-CE uptake and accumulation in
      cardiomyocytes.

PMID- 22454365
TI  - Osteogenic differentiation of osteoblasts induced by calcium silicate and calcium
      silicate/beta-tricalcium phosphate composite bioceramics.
AB  - In this study, calcium silicate (CS) and CS/beta-tricalcium phosphate (CS/beta
      TCP) composites were investigated on their mechanism of osteogenic proliferation
      and differentiation through regulating osteogenic-related gene and proteins.
      Osteoblast-like cells were cultured in the extracts of these CS-based bioceramics
      and pure beta-TCP, respectively. The main ionic content in extracts was analyzed
      by inductively coupled plasma-atomic emission spectroscopy. The cell viability,
      mineralization, and differentiation were evaluated by MTT assay, Alizarin Red-S
      staining and alkaline phosphatase (ALP) activity assay. The expressions of BMP-2,
      transforming growth factor-beta (TGF-beta), Runx2, ALP, and osteocalcin (OCN) at
      both gene and protein level were detected by real-time polymerase chain reaction
      analysis and Western blot. The result showed that the extracts of CS-based
      bioceramics promoted cells proliferation, differentiation, and mineralization
      when compared with pure beta-TCP. Accordingly, pure CS and CS/beta-TCP composites
      stimulated osteoblast-like cells to express BMP-2/TGF-beta gene and proteins, and
      further regulate the expression of Runx2 gene and protein, and ultimately affect
      the ALP activity and OCN deposition. This study suggested that the CS-based
      bioceramics could not only promote the expression of osteogenic-related genes but
      also enhance the genes to encode the corresponding proteins, which could finally
      control osteoblast-like cells proliferation and differentiation.

PMID- 22454364
TI  - Association of AKI with mortality and complications in hospitalized patients with
      cirrhosis.
AB  - Acute kidney injury (AKI) is a common and devastating complication in patients
      with cirrhosis. However, the definitions of AKI employed in studies involving
      patients with cirrhosis have not been standardized, lack sensitivity, and are
      often limited to narrow clinical settings. We conducted a multicenter,
      prospective observational cohort study of patients with cirrhosis and AKI, drawn
      from multiple hospital wards, utilizing the modern acute kidney injury network
      (AKIN) definition and assessed the association between AKI severity and
      progression with in-hospital mortality. Of the 192 patients who were enrolled and
      included in the study, 85 (44%) progressed to a higher AKIN stage after initially
      fulfilling AKI criteria. Patients achieved a peak severity of AKIN stage 1, 26%,
      stage 2, 24%, and stage 3, 49%. The incidence of mortality, general medical
      events (bacteremia, pneumonia, urinary tract infection), and cirrhosis-specific
      complications (ascites, encephalopathy, spontaneous bacterial peritonitis)
      increased with severity of AKI. Progression was significantly more common and
      peak AKI stage higher in nonsurvivors than survivors (P < 0.0001). After
      adjusting for baseline renal function, demographics, and critical hospital- and
      cirrhosis-associated variables, progression of AKI was independently associated
      with mortality (adjusted odds ratio = 3.8, 95% confidence interval 1.3-11.1).
      CONCLUSION: AKI, as defined by AKIN criteria, in patients with cirrhosis is
      frequently progressive and severe and is independently associated with mortality
      in a stage-dependent fashion. Methods for earlier diagnosis of AKI and its
      progression may result in improved outcomes by facilitating targeted and timely
      treatment of AKI.

PMID- 22454366
TI  - Robotic transaxillary thyroidectomy with gasless approach in a girl with goitre.
AB  - BACKGROUND: Robotic-assisted transaxillary thyroidectomy is a minimally invasive
      approach for the removal of the thyroid through the axilla. This technique
      eliminates a visible scar and affords excellent optics of the cervical anatomy.
      We sought to describe the technique and outcome for transaxillary gasless
      subtotal thyroidectomy in the paediatric population. METHODS: A 13 year-old
      female with an enlarged goitre underwent a transaxillary robot-assisted gasless
      subtotal thyroidectomy in an academic institution. The main outcome measures were
      feasibility of the robotic approach, patient and gland characteristics, operative
      time and complications. RESULTS: There was no conversion to laparoscopic or open
      surgery. The robotic docking time was 110 min and total operative time was 150
      min. The patient tolerated the procedure well. Estimated blood loss was 10 ml.
      The patient was discharged within 24 h. There were no perioperative or
      postoperative complications. In addition there was no evidence of postoperative
      vocal cord palsy or paresis. CONCLUSIONS: This initial experience demonstrates
      that this technique can be a feasible, safe and effective method for subtotal
      thyroidectomy in the paediatric population. The use of robotic technology for
      endoscopic thyroid surgery could overcome the limitations of conventional
      endoscopic surgeries in the surgical management of thyroid disease.

PMID- 22454367
TI  - Palladium-catalyzed annulation of 1,2-diborylalkenes and -arenes with 1-bromo-2
      [(Z)-2-bromoethenyl]arenes: a modular approach to multisubstituted naphthalenes
      and fused phenanthrenes.
AB  - (Z)-1,2-Diaryl-1,2-bis(pinacolatoboryl)ethenes underwent double-cross-coupling
      reactions with 1-bromo-2-[(Z)-2-bromoethenyl]arenes in the presence of
      [Pd(PPh(3))(4)] as a catalyst and 3 M aqueous Cs(2)CO(3) as a base in THF at 80 
      degrees C. The double-coupling reaction gave multisubstituted naphthalenes in
      good to high yields. Annulation of 1,2-bis(pinacolatoboryl)arenes with
      bromo(bromoethenyl)arenes in the presence of a catalyst system that consisted of
      [Pd(2)(dba)(3)] (dba=dibenzylideneacetone) and 2-dicyclohexylphosphino-2',6'
      dimethoxybiphenyl (SPhos) under the same conditions produced fused phenanthrenes
      in good to high yields. The first annulation coupling occurred regiospecifically
      at the bromoethenyl moiety. This procedure is applicable to the facile synthesis
      of polysubstituted anthracenes, benzothiophenes, and dibenzoanthracenes through a
      double annulation pathway by using the corresponding dibromobis[(Z)-2
      bromoethenyl]benzenes as diboryl coupling partners.

PMID- 22454368
TI  - Molecular tethering or aggregation: is the existence of charge-transfer bands
      indicative of the formation of blue-box/tetrathiafulvalene inclusion complexes?
AB  - The interaction between tetrathiafulvalene and tetracation cyclobis(paraquat-p
      phenylene) fragments-the key elements of many rotaxane systems-was investigated
      theoretically by using ab-initio second-order perturbation methods. In addition
      to the inclusion complex observed in the solid state, a thermodynamically stable
      "exterior" complex was identified. Calculation of the UV/Vis spectra for the
      inclusion and the exterior complexes indicated that the charge-transfer band that
      is often used to predict the formation of the inclusion complexes in solution is,
      in reality, due to the exterior mode of complexation. These results suggest that
      UV/Vis spectroscopy is not a reliable method for assigning the complexation modes
      in TTF:BB(4+) rotaxanes and related systems.

PMID- 22454369
TI  - Genes, environments, personality, and successful aging: toward a comprehensive
      developmental model in later life.
AB  - BACKGROUND: Outcomes in aging and health research, such as longevity, can be
      conceptualized as reflecting both genetic and environmental (nongenetic) effects.
      Parsing genetic and environmental influences can be challenging, particularly
      when taking a life span perspective, but an understanding of how genetic variants
      and environments relate to successful aging is critical to public health and
      intervention efforts. METHODS: We review the literature, and survey promising
      methods, to understand this interplay. We also propose the investigation of
      personality as a nexus connecting genetics, environments, and health outcomes.
      RESULTS: Personality traits may reflect psychological mechanisms by which
      underlying etiologic (genetic and environmental) effects predispose individuals
      to broad propensities to engage in (un)healthy patterns of behavior across the
      life span. In terms of methodology, traditional behavior genetic approaches have
      been used profitably to understand how genetic factors and environments relate to
      health and personality in somewhat separate literatures; we discuss how other
      behavior genetic approaches can help connect these literatures and provide new
      insights. CONCLUSIONS: Co-twin control designs can be employed to help determine
      causality via a closer approximation of the idealized counterfactual design. Gene
      by-environment interaction (G * E) designs can be employed to understand how
      individual difference characteristics, such as personality, might moderate
      genetic and environmental influences on successful aging outcomes. Application of
      such methods can clarify the interplay of genes, environments, personality, and
      successful aging.

PMID- 22454370
TI  - The genetics of age-related health outcomes.

PMID- 22454371
TI  - Association between serum 25(OH) vitamin D and the risk of cognitive decline in
      older women.
AB  - BACKGROUND: Results of prospective studies examining the association between 25
      hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent.
      We tested the hypothesis that lower 25(OH)D levels are associated with a greater
      likelihood of cognitive impairment and risk of cognitive decline. METHODS: The
      study is a cross-sectional and longitudinal analysis of a prospective cohort of
      6,257 community-dwelling elderly women followed for 4 years. Global cognitive
      function was measured by the Modified Mini-Mental State Examination and executive
      function was measured by Trail Making Test Part B (Trails B). Cognitive
      impairment at baseline was defined as a score >1.5 SD below the sample mean;
      cognitive decline was defined as decline from baseline to follow-up >1 SD from
      mean change in score. RESULTS: Women with very low vitamin D levels had an
      increased odds of global cognitive impairment at baseline: odds ratio (95%
      confidence interval), 1.60 (1.05-2.42) for women with 25(OH)D <10 ng/mL (25
      nmol/L) compared with those with 25(OH)D levels >=30 ng/mL (75 nmol/L). Compared
      with women with baseline 25(OH)D level >=30 ng/mL (75 nmol/L), women with lower
      levels had an increased risk of global cognitive decline: odds ratio (95%
      confidence interval), 1.58(1.12-2.22) for women with levels <10 ng/mL (25
      nmol/L), and 1.31 (1.04-1.64) for those with levels 10-19.9 ng/mL (25-49 nmol/L).
      Levels of 25(OH)D were not associated with executive cognitive function.
      CONCLUSIONS: Low 25(OH)D levels among older women were associated with a higher
      odds of global cognitive impairment and a higher risk of global cognitive
      decline.

PMID- 22454372
TI  - Calorie restriction enhances insulin-stimulated glucose uptake and Akt
      phosphorylation in both fast-twitch and slow-twitch skeletal muscle of 24-month
      old rats.
AB  - Calorie restriction (CR) induces enhanced insulin-stimulated glucose uptake in
      fast-twitch (type II) muscle from old rats, but the effect of CR on slow-twitch
      (type I) muscle from old rats is unknown. The purpose of this study was to assess
      insulin-stimulated glucose uptake and phosphorylation of key insulin signaling
      proteins in isolated epitrochlearis (fast-twitch) and soleus (slow-twitch)
      muscles from 24-month-old ad libitum fed and CR (consuming 65% of ad libitum,
      intake) rats. Muscles were incubated with and without 1.2 nM insulin. CR versus
      ad libitum rats had greater insulin-stimulated glucose uptake and Akt
      phosphorylation (pAkt) on T308 and S473 for both muscles incubated with insulin.
      GLUT4 protein abundance and phosphorylation of the insulin receptor (Y1162/1163)
      and AS160 (T642) were unaltered by CR in both muscles. These results implicate
      enhanced pAkt as a potential mechanism for the CR-induced increase in insulin
      stimulated glucose uptake by the fast-twitch epitrochlearis and slow-twitch
      soleus of old rats.

PMID- 22454373
TI  - Differential effects of stimulatory factors on natural killer cell activities of
      young and aged mice.
AB  - Age-associated influences on natural killer (NK) cell functions following
      cytokine stimulation were examined in splenocytes from C57BL/6 mice. NK cells of
      both young and aged mice exhibited significantly increased: interferon-gamma
      production after interleukin (IL)-12 or IL-15 alone or any combination of IL-12,
      IL-18, and IL-2; cytotoxicity after IL-2 or IL-15; and granzyme B expression
      after IL-15. The only significant age-associated differences were observed in
      interferon-gamma production after IL-15 or IL-12 + 18 + 2 and in granzyme B
      expression following IL-2 or IL-15. Perforin expression did not increase
      following stimulation; however, NK cells from aged mice expressed significantly
      higher levels than young mice. These results underscore the complexity of the
      cytokine-induced functional activities of NK cells and illustrate the
      differential response of NK cells from young and aged mice to cytokine
      stimulation.

PMID- 22454375
TI  - The longitudinal relationship between depressive symptoms and disability for
      older adults: a population-based study.
AB  - BACKGROUND: Although depressive symptoms in older adults are common, their
      relationship with disability and the influence of disability on the development
      of depressive symptoms over time is not well understood. This longitudinal study
      investigates the change trajectories of both depressive symptoms and disability,
      as well as their associations over time. METHODS: Participants included 442
      community-dwelling older adults living in Taiwan, aged 65 years or older, who
      completed six waves of survey interviews. Depression was scored with the Short
      Psychiatric Evaluation Schedule and disability with the instrumental and physical
      activities of daily living measure during each consecutive data collection wave.
      The autoregressive latent trajectory model and parallel latent growth curve
      modeling were adopted for analysis of the data. RESULTS: The autoregressive
      latent trajectory model highlights that previous depressive symptoms (and
      disability) significantly contributed to the advancement of more severe
      depressive symptoms (and disability). This model also indicates that disability
      significantly contributed to the onset of depressive symptoms and vice versa. The
      parallel latent growth curve modeling highlights that the disability intercept
      had significant effects on the depressive symptoms intercept, as did the
      depressive symptoms on disability. Furthermore, the disability slope had
      significant effects on the slope of the depressive symptoms. CONCLUSIONS: These
      findings demonstrate that disability is a stronger predictor of depressive
      symptoms than depressive symptoms are of disability. In addition, the prior
      existence of a health condition will lead to further deterioration of health
      conditions and that they often coexist.

PMID- 22454376
TI  - Older people with hip fracture and IADL disability require earlier surgery.
AB  - BACKGROUND: Hip fractures represent a major challenge for physicians as well as
      society as a whole. Both poor functional status and delay to surgery are well
      known risk factors for negative outcomes. We hypothesized that the timing of the
      operation is more important for frail older people than older people without
      functional limitations before fracture. METHODS: We performed a prospective
      multicenter cohort study on 806 consecutive patients, 75 years of age or older,
      admitted with a fragility hip fracture to three hospitals in the Emilia-Romagna
      Region (Italy). All three hospitals had a comanaged care model, and the patients
      were under the shared responsibility of an orthopedic surgeon and a geriatrician.
      RESULTS: Functional status assessed as instrumental activities of daily living
      was an important predictor of survival after 1 year from fracture. After
      adjusting for confounders, the hazard ratios per 1 point score of increase from 0
      to 8 was 1.30 (95% confidence interval 1.19-1.42, p = .000). Time to surgery
      increased 1-year mortality in patients with a low instrumental activities of
      daily living score (hazard ratios per day of surgical delay 1.14, 95% confidence
      interval 1.06-1.22, p < .001) and intermediate instrumental activities of daily
      living score (hazard ratios 1.21, 95% confidence interval 1.09-1.34, p < .001)
      but was an insignificant risk factor in functionally independent patients (hazard
      ratios 1.05 95% confidence interval 0.79-1.41, p = .706). CONCLUSIONS: Surgery
      delay is an independent factor for mortality in older patients after hip fracture
      but only for the frail older people with prefracture functional impairment. If
      our results are confirmed, a more intensive approach should be adopted for older
      people with hip fractures who have disabilities.

PMID- 22454374
TI  - Genomics and successful aging: grounds for renewed optimism?
AB  - BACKGROUND: Successful aging depends in part on delaying age-related disease
      onsets until later in life. Conditions including coronary artery disease,
      Alzheimer's disease, prostate cancer, and type 2 diabetes are moderately
      heritable. Genome-wide association studies have identified many risk associated
      single-nucleotide polymorphisms for these conditions, but much heritability
      remains unaccounted for. Nevertheless, a great deal is being learned. METHODS:
      Here, we review age-related disease associated single-nucleotide polymorphisms
      and identify key underlying pathways including lipid handling, specific immune
      processes, early tissue development, and cell cycle control. RESULTS: Most age
      related disease associated single-nucleotide polymorphisms do not affect coding
      regions of genes or protein makeup but instead influence regulation of gene
      expression. Recent evidence indicates that evolution of gene regulatory sites is
      fundamental to interspecies differences. Animal models relevant to human aging
      may therefore need to focus more on gene regulation rather than testing major
      disruptions to fundamental pathway genes. Recent larger scale human studies of in
      vivo genome-wide expression (notably from the InCHIANTI aging study) have
      identified changes in splicing, the "fine tuning" of protein sequences, as a
      potentially important factor in decline of cellular function with age. Studies of
      expression with muscle strength and cognition have shown striking concordance
      with certain mice models of muscle repair and beta-amyloid phagocytosis
      respectively. CONCLUSIONS: The emerging clearer picture of the genetic
      architecture of age-related diseases in humans is providing new insights into the
      underlying pathophysiological pathways involved. Translation of genomics into new
      approaches to prevention, tests and treatments to extend successful aging is
      therefore likely in the coming decades.

PMID- 22454377
TI  - Cyclin E1 controls proliferation of hepatic stellate cells and is essential for
      liver fibrogenesis in mice.
AB  - Liver fibrogenesis is associated with the transition of quiescent hepatocytes and
      hepatic stellate cells (HSCs) into the cell cycle. Exit from quiescence is
      controlled by E-type cyclins (cyclin E1 [CcnE1] and cyclin E2 [CcnE2]). Thus, the
      aim of the current study was to investigate the contribution of E-type cyclins
      for liver fibrosis in man and mice. Expression of CcnE1, but not of its homolog,
      CcnE2, was induced in fibrotic and cirrhotic livers from human patients with
      different etiologies and in murine wild-type (WT) livers after periodical
      administration of the profibrotic toxin, CCl(4). To further evaluate the
      potential function of E-type cyclins for liver fibrogenesis, we repetitively
      treated constitutive CcnE1(-/-) and CcnE2(-/-) knock-out mice with CCl(4) to
      induce liver fibrosis. Interestingly, CcnE1(-/-) mice were protected against
      CCl(4)-mediated liver fibrogenesis, as evidenced by reduced collagen type I
      alpha1 expression and the lack of septum formation. In contrast, CcnE2(-/-) mice
      showed accelerated fibrogenesis after CCl(4) treatment. We isolated primary HSCs
      from WT, CcnE1(-/-), and CcnE2(-/-) mice and analyzed their activation,
      proliferation, and survival in vitro. CcnE1 expression in WT HSCs was maximal
      when they started to proliferate, but decreased after the cells
      transdifferentiated into myofibroblasts. CcnE1(-/-) HSCs showed dramatically
      impaired survival, cell-cycle arrest, and strongly reduced expression of alpha
      smooth muscle actin, indicating deficient HSC activation. In contrast, CcnE2
      deficient HSCs expressed an elevated level of CcnE1 and showed enhanced cell
      cycle activity and proliferation, compared to WT cells. CONCLUSIONS: CcnE1 and
      CcnE2 have antagonistic roles in liver fibrosis. CcnE1 is indispensable for the
      activation, proliferation, and survival of HSCs and thus promotes the synthesis
      of extracellular matrix and liver fibrogenesis.

PMID- 22454378
TI  - Association between reproductive factors and urinary estrogens and estrogen
      metabolites in premenopausal women.
AB  - BACKGROUND: Little is known about relationships among reproductive factors,
      estrogens and estrogen metabolites (jointly referred to as EM), and estrogen
      metabolism patterns. METHODS: In a cross-sectional analysis, we examined the
      associations of age at menarche, menstrual cycle length and regularity, parity,
      age at first and last birth, breastfeeding, and duration of and time since use of
      oral contraceptives with mid-luteal phase urinary EM in a sample of 603
      premenopausal women, ages 33 to 51 years, within the Nurses' Health Study II
      (NHSII). Fifteen individual urinary EMs were measured with liquid
      chromatography/tandem mass spectrometry (LC/MS-MS) and analyzed both individually
      and in metabolic pathways. RESULTS: Compared with women with extremely regular
      cycles, those with irregular cycles had lower levels of total EM (percent
      difference = 24%; P(trend) = 0.01), estradiol (23%; P(trend) = 0.02), and 16
      hydroxylation pathway EM (32%; P(trend) < 0.01). Longer menstrual cycles were
      associated with higher levels of estrone (percent difference >=32 vs. <26 days:
      25%; P(trend) = 0.03), estradiol (24%; P(trend) = 0.01), and 16-hydroxylation
      pathway EM (22%; P(trend) = 0.02). Among parous women, older age at first birth
      was associated with lower 16-hydroxylation pathway EM (percent difference age at
      first birth >35 vs. <=25 years: 20%; P(trend) = 0.02). The other reproductive
      factors were not statistically significantly associated with individual urinary
      EM or EM pathways. CONCLUSIONS AND IMPACT: These data, based on a LC/MS-MS assay
      with high specificity and precision, provide an initial, comprehensive evaluation
      of the associations between reproductive factors and estrogen metabolism
      patterns.

PMID- 22454380
TI  - Leaf epidermal features of Salix species (Salicaceae) and their systematic
      significance.
AB  - PREMISE OF THE STUDY: The classification of the genus Salix has historically been
      intrinsically difficult due to its propensity toward plasticity and high
      variation in diagnostic morphological characters. We investigated leaf epidermal
      characteristics, focusing on the stomatal apparatus because it may provide
      critical insights into the evolution and taxonomy of Salix and its closely
      related genera. METHODS: Light microscopy was used to examine the leaf epidermal
      features in 32 taxa of Salix. KEY RESULTS: Characters such as shape, size, and
      density of stomatal complexes were very useful in differentiating Salix species.
      Variation in features of stomatal apparatus in Salix is wider than previously
      known. Moreover, the type of stomatal complex proved to be very helpful in
      discriminating Chosenia as members of the genus Salix. CONCLUSIONS: The results
      of the present study support the placement of Chosenia within Salix and the
      combining of subgenera Chamaetia and Vetrix because of similarities in their
      unique stomatal apparatus.

PMID- 22454381
TI  - Isolation and characterization of microsatellite loci in the endangered tree
      Diplopanax stachyanthus (Araliaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed in Diplopanax
      stachyanthus to investigate the population genetics of this endangered tree.
      METHODS AND RESULTS: Using the Fast Isolation by AFLP of Sequences Containing
      repeats (FIASCO) protocol, 15 microsatellite markers were developed in D.
      stachyanthus and evaluated for their variability in 25 samples from a natural
      population. For the 11 polymorphic loci, the number of alleles ranged from two to
      eight, while the observed and expected heterozygosities ranged from 0.5200 to
      0.7600 and 0.4200 to 0.7813, respectively. Their cross-taxa transferability was
      also examined in Acanthopanax gracilistylus, Tetrapanax papyrifer, Cornus
      controversa, and Dendrobenthamia japonica var. chinensis, and four to 15 loci
      proved amplifiable in these species. CONCLUSIONS: These microsatellite markers
      could be employed to investigate the population genetics of D. stachyanthus, and
      may potentially be applicable to other related species.

PMID- 22454382
TI  - Microsatellites in Aureliana fasciculata var. fasciculata (Solanaceae), a shrub
      that inhabits the Atlantic Rainforest.
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed in Aureliana
      fasciculata var. fasciculata, a shrub that inhabits the Atlantic Rainforest, to
      investigate the intraspecific genetic structure of the species. METHODS AND
      RESULTS: Nine pairs of microsatellite primers were designed that were based on a
      simple sequence repeat (SSR)-enriched library. Seven loci were amplified
      successfully. Two populations of A. fasciculata var. fasciculata were genotyped
      and all loci were polymorphic, with two to five alleles per locus per population
      detected. Cross-species amplification was achieved in other members of the genus
      and members of the sister genus Athenaea. CONCLUSIONS: The development of these
      microsatellite markers will contribute to future population genetic studies in A.
      fasciculata var. fasciculata. Cross-amplification among other species in the
      genus and in the sister genus Athenaea might be a useful tool to establish
      patterns of genetic variability within the Atlantic Rainforest.

PMID- 22454379
TI  - Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated
      with mammographic density measures that predict breast cancer risk.
AB  - BACKGROUND: Mammographic density adjusted for age and body mass index (BMI) is a
      heritable marker of breast cancer susceptibility. Little is known about the
      biologic mechanisms underlying the association between mammographic density and
      breast cancer risk. We examined whether common low-penetrance breast cancer
      susceptibility variants contribute to interindividual differences in mammographic
      density measures. METHODS: We established an international consortium (DENSNP) of
      19 studies from 10 countries, comprising 16,895 Caucasian women, to conduct a
      pooled cross-sectional analysis of common breast cancer susceptibility variants
      in 14 independent loci and mammographic density measures. Dense and nondense
      areas, and percent density, were measured using interactive-thresholding
      techniques. Mixed linear models were used to assess the association between
      genetic variants and the square roots of mammographic density measures adjusted
      for study, age, case status, BMI, and menopausal status. RESULTS: Consistent with
      their breast cancer associations, the C-allele of rs3817198 in LSP1 was
      positively associated with both adjusted dense area (P = 0.00005) and adjusted
      percent density (P = 0.001), whereas the A-allele of rs10483813 in RAD51L1 was
      inversely associated with adjusted percent density (P = 0.003), but not with
      adjusted dense area (P = 0.07). CONCLUSION: We identified two common breast
      cancer susceptibility variants associated with mammographic measures of
      radiodense tissue in the breast gland. IMPACT: We examined the association of 14
      established breast cancer susceptibility loci with mammographic density
      phenotypes within a large genetic consortium and identified two breast cancer
      susceptibility variants, LSP1-rs3817198 and RAD51L1-rs10483813, associated with
      mammographic measures and in the same direction as the breast cancer association.

PMID- 22454383
TI  - Systematics and evolution of Arctic-Alpine Arabis alpina (Brassicaceae) and its
      closest relatives in the eastern Mediterranean.
AB  - PREMISE OF THE STUDY: The high mountains in southern Anatolia and the eastern
      Mediterranean are assumed to play a major role as a primary center of genetic
      diversity and species richness in Eurasia. We tested this hypothesis by focusing
      on the widespread perennial arctic-alpine Arabis alpina and its sympatrically
      distributed closest relatives in the eastern Mediterranean. METHODS: Plastid
      (trnL intron, trnL-F intergenic spacer) and nuclear (ITS) DNA sequence analysis
      was used for phylogenetic reconstruction. Broad-scale plastid haplotype analyses
      were conducted to infer ancestral biogeographic patterns. KEY RESULTS: Five
      Arabis species, identified from the eastern Mediterranean (Turkey mainland and
      Cyprus), evolved directly and independently from A. alpina, leaving Arabis alpina
      as a paraphyletic taxon. These species are not affected by hybridization or
      introgression, and species divergence took place at the diploid level during the
      Pleistocene. CONCLUSIONS: Pleistocene climate fluctuations produced local
      altitudinal range-shifts among mountain glacial survival areas, resulting not
      only in the accumulation of intraspecific genotype diversity but also in the
      formation of five local species. We also show that the closest sister group of
      Arabis alpina consists exclusively of annuals/winter annuals and diverged prior
      to Pleistocene climatic fluctuations during the colonization of the lowland
      Mediterranean landscape. These findings highlight that Anatolia is not only a
      center of species richness but also a center for life-history diversification.

PMID- 22454384
TI  - Morphological response to competition for light in the clonal Trifolium repens
      (Fabaceae).
AB  - PREMISE OF THE STUDY: Plant communities in temperate zones are dominated by
      clonal plants that can plastically modify their growth characteristics in
      response to competition. Given that plants compete with one another, and the
      implications this has for species coexistence, we conducted a study to assess how
      clonal species morphologically respond to competition for light depending on its
      intensity and heterogeneity, which are determined by the competitor species.
      METHODS: We assessed the morphological response to competition for light of the
      clonal species Trifolium repens L. by measuring its growth performance, and
      vertical and horizontal growth traits. We used five competitive environments,
      i.e., one without competitor and four differing by their competitor species
      creating different conditions of competition intensity and heterogeneity. KEY
      RESULTS: The morphological response of Trifolium repens to competition for light
      depended on the competitor identity. Competition intensity and heterogeneity,
      determined by competitor identity, had an interactive effect on most traits. The
      increase in petiole elongation and specific leaf area due to increased
      competition intensity was observed only at low to intermediate competition
      heterogeneity. Competition heterogeneity promoted the elongation of clone
      connections allowing space exploration. CONCLUSIONS: Our results demonstrated
      that the intensity and heterogeneity of competition, which depended on competitor
      identity, are of primary importance in determining the plastic response of
      Trifolium repens. This emphasizes that it is important to consider the fine-scale
      spatial distribution of individuals when studying their interactions within plant
      communities.

PMID- 22454385
TI  - Cryptorchidism and hypospadias in a cohort of 934,538 Danish boys: the role of
      birth weight, gestational age, body dimensions, and fetal growth.
AB  - Early delivery and low birth weight are strong predictors of the urogenital
      anomalies cryptorchidism (undescended testis) and hypospadias. Understanding
      these associations may lead to important etiologic clues. Therefore, the authors
      revisited the prevailing hypotheses regarding fetal growth restriction as a risk
      factor for urogenital anomalies. They studied a population of 934,538 Danish boys
      born alive between January 1, 1980, and December 31, 2008. Cryptorchidism and
      hypospadias were associated with low weight-for-gestational-age, an indicator of
      fetal growth restriction, and furthermore the authors observed strong interaction
      with early delivery. Low birth weight in a singleton compared with the mean birth
      weight of all singleton brothers in the family or in a twin compared with the
      male co-twin was associated with higher risk of urogenital anomalies, suggesting
      an effect of relative fetal growth restriction within families. Contrary to
      previous reports, newborns' body dimensions assessed independently of birth
      weight were not associated with urogenital anomalies. The hypothesis that shared
      factors cause both fetal growth restriction and urogenital anomalies was
      supported by comparison of urogenital anomaly risks in singletons and twins and
      by patterns of cryptorchidism and hypospadias co-occurrence in individuals. These
      novel insights might also extend to other male reproductive conditions with
      prenatal etiology.

PMID- 22454386
TI  - Contributing to others, contributing to oneself: perceptions of generativity and
      health in later life.
AB  - OBJECTIVES: To examine whether perceptions of generativity predict the likelihood
      of increases in levels of impairment in activities of daily living (ADLs) or of
      dying over a 10-year period in older adults aged 60-75 from the Study of Midlife
      in the United States (MIDUS). METHOD: Perceptions of generativity and current
      generative contributions as well as select sociodemographic, health status,
      health behavior, and psychosocial factors, assessed at a baseline exam, were
      examined as predictors of change in ADL disability level or mortality over the 10
      year period between the baseline and follow-up waves of the MIDUS Study. RESULTS:
      Greater levels of generativity and generative contributions at baseline predicted
      lower odds of experiencing increases in ADL disability (2 or more new domains of
      impairment; generativity odds ratio [OR] = 0.93 and generative contributions OR =
      0.87), or of dying (generativity OR = 0.94 and generative contributions OR =
      0.88), over the 10-year follow-up in models adjusted for sociodemographics and
      baseline health and disability. Associations remained relatively unchanged with
      the inclusion of different sets of health behavior and psychosocial variables in
      analytic models. DISCUSSION: Findings indicate that greater perceptions of
      generativity are associated with more favorable trajectories of physical
      functioning and longevity over time in older adults.

PMID- 22454387
TI  - The effect of bilingualism on amnestic mild cognitive impairment.
AB  - OBJECTIVES: Previous reports have found that lifelong bilingualism is associated
      with a delay in the onset of dementia, including Dementia of the Alzheimer's Type
      (DAT). Because amnestic mild cognitive impairment (aMCI) is often a transition
      stage between normal aging and DAT, our aim in this paper was to establish
      whether this delay in symptom onset for bilinguals would also be seen in the
      onset of symptoms of aMCI and whether this delay would be consistent in different
      subtypes of aMCI. METHOD: We examined the effect of bilingualism on the age of
      diagnosis in individuals with single- or multiple-domain aMCI who were
      administered a battery of neuropsychological tests and questionnaires about their
      language and social background. RESULTS: Our results showed an interaction
      between aMCI type and language history. Only individuals diagnosed with single
      domain aMCI demonstrated a later age of diagnosis for bilinguals (M = 79.4 years)
      than monolinguals (M = 74.9 years). DISCUSSION: This preliminary evidence
      suggests that the early protective advantage of bilingualism may be specific to
      single-domain aMCI, which is the type of aMCI most specifically associated with
      progression to DAT.

PMID- 22454388
TI  - The impact of transportation support on driving cessation among community
      dwelling older adults.
AB  - OBJECTIVES: This study longitudinally examines the impact of transportation
      support on driving cessation among community-dwelling older adults residing in
      retirement communities. METHOD: Data came from 3 waves of the Florida Retirement
      Study (1990-1992), a population-based cohort study. Analysis was limited to
      participants who drove at baseline and were reinterviewed in 1992 (N = 636).
      Transportation support from a spouse, family members, friends/neighbors,
      agencies/organizations (e.g., church), or hired assistants was included. Discrete
      time multivariate hazard models were estimated to examine the impact of
      transportation support on driving cessation while controlling for demographic and
      health characteristics. RESULTS: Participants were more likely to stop driving if
      they had received at least some transportation support from friends/neighbors
      (Hazard Ratio = 2.49, p = .001) as compared with those with little or no support.
      Transportation support from organizations/agencies or hired assistants was also
      significantly associated with the likelihood of driving cessation, but only a
      small number of participants reported to have received such support. Receiving
      some or more transportation support from a spouse or family members did not have
      a statistically significant relationship with driving cessation. DISCUSSION: The
      findings suggest that available nonkin transportation support, particularly
      support from peer friends, plays an important role in driving cessation for older
      adults living in retirement communities.

PMID- 22454389
TI  - The use of the operand-recognition paradigm for the study of mental addition in
      older adults.
AB  - OBJECTIVES: Determining how individuals solve arithmetic problems is crucial for
      our understanding of human cognitive architecture. Elderly adults are supposed to
      use memory retrieval more often than younger ones. However, they might backup
      their retrieval by reconstructive strategies. In order to investigate this issue,
      we used the operand-recognition paradigm, which capitalizes on the fact that
      algorithmic procedures degrade the memory traces of the operands. METHOD: Twenty
      three older adults (M = 70.4) and 23 younger adults (M = 20.0) solved easy,
      difficult, and medium-difficulty addition and comparison problems and were then
      presented with a recognition task of the operands. RESULTS: When one-digit
      numbers with sums larger than 10 were involved (medium-difficulty problem), it
      was more difficult for younger adults to recognize the operands after addition
      than comparison. In contrast, in older adults, recognition times of the operands
      were the same after addition and comparison. DISCUSSION: Older adults, in
      contrast with younger adults, are able to retrieve the results of addition
      problems of medium difficulty. Contrary to what was suggested, older participants
      do not seem to resort to backup strategies for such problems. Finally, older
      adults' reliance on the more efficient retrieval strategy allowed them to catch
      up to younger adults in terms of solution times.

PMID- 22454390
TI  - Determination of bupropion using liquid chromatography with fluorescence
      detection in pharmaceutical preparations, human plasma and human urine.
AB  - A novel pre-column derivatization reversed-phase high-performance liquid
      chromatography with fluorescence detection is described for the determination of
      bupropion in pharmaceutical preparation, human plasma and human urine using
      mexiletine as internal standard. The proposed method is based on the reaction of
      4-chloro-7-nitrobenzofurazan (NBD-Cl) with bupropion to produce a fluorescent
      derivative. The derivative formed is monitored on a C18 (150 mm * 4.6 mm i.d., 5
      um) column using a mobile phase consisting of methanol-water 75:25 (v/v), at a
      flow-rate of 1.2 mL/min and detected fluorimetrically at lambda(ex) = 458 and
      lambda(em) = 533 nm. The assay was linear over the concentration ranges of 5-500
      and 10-500 ng/mL for plasma and urine, respectively. The limits of detection and
      quantification were calculated to be 0.24 and 0.72 ng/mL for plasma and urine,
      respectively (inter-day results). The recoveries obtained for plasma and urine
      were 97.12% +/- 0.45 and 96.00% +/- 0.45, respectively. The method presents good
      performance in terms of precision, accuracy, specificity, linearity, detection
      and quantification limits and robustness. The proposed method is applied to
      determine bupropion in commercially available tablets. The results were compared
      with an ultraviolet spectrophotometry method using t- and F-tests.

PMID- 22454391
TI  - A validated LC method for determination of 2,3-dichlorobenzoic acid and its
      associated regio isomers.
AB  - A simple, selective and sensitive gradient reversed-phase liquid chromatography
      method has been developed for the separation and determination of 2,3
      dichlorobenzoic acid, which is an intermediate of the lamotrizine drug substance,
      and its regio isomers. The separation was achieved on a reversed-phase United
      States Pharmacopeia L1 (C-18) column using 0.01 M ammonium acetate buffer at pH
      2.5 and methanol (50:50 v/v) mixture as mobile phase A and a methanol and water
      mixture (80:20 v/v) as mobile phase B in a gradient elution at flow rate 1.2
      mL/min with ultraviolet detection at 210 nm. The method is found to be selective,
      precise, linear, accurate and robust. It was used for quality assurance and
      monitoring the synthetic reactions involved in the process development of
      lamotrizine. The method is found to be simple, rapid, specific and reliable for
      the determination of unreacted levels of raw materials and isomers in reaction
      mixtures and finished product lamotrizine. The method was fully validated as per
      International Conference of Harmonization guidelines and results from validation
      confirm that the method is highly suitable for its intended purpose.

PMID- 22454392
TI  - Health disparities grants funded by National Institute on Aging: trends between
      2000 and 2010.
AB  - PURPOSE OF THE STUDY: The present study examined the characteristics of health
      disparities grants funded by National Institute on Aging (NIA) from 2000 to 2010.
      Objectives were (a) to examine longitudinal trends in health disparities-related
      grants funded by NIA and (b) to identify moderators of these trends. DESIGN AND
      METHODS: Our primary data source was the National Institutes of Health Research
      Portfolio Online Reporting Tools Expenditures and Results (RePORTER) system. The
      RePORTER data were merged with data from the Carnegie Classification of
      Institutions of Higher Education. General linear models were used to examine the
      longitudinal trends and how these trends were associated with type of grant and
      institutional characteristics. RESULTS: NIA funded 825 grants on health
      disparities between 2000 and 2010, expending approximately 330 million dollars.
      There was an overall linear increase over time in both the total number of grants
      and amount of funding, with an outlying spike during 2009. These trends were
      significantly influenced by several moderators including funding mechanism and
      type of institution. IMPLICATIONS: The findings highlight NIA's current efforts
      to fund health disparities grants to reduce disparities among older adults.
      Gerontology researchers may find this information very useful for their future
      grant submissions.

PMID- 22454393
TI  - IL-33 independently induces eosinophilic pericarditis and cardiac dilation: ST2
      improves cardiac function.
AB  - BACKGROUND: IL-33 through its receptor ST2 protects the heart from myocardial
      infarct and hypertrophy in animal models but, paradoxically, increases autoimmune
      disease. In this study, we examined the effect of IL-33 or ST2 administration on
      autoimmune heart disease. METHODS AND RESULTS: We used pressure-volume
      relationships and isoproterenol challenge to assess the effect of recombinant (r)
      IL-33 or rST2 (eg, soluble ST2) administration on the development of autoimmune
      coxsackievirus B3 myocarditis and dilated cardiomyopathy in male BALB/c mice. The
      rIL-33 treatment significantly increased acute perimyocarditis (P=0.006) and
      eosinophilia (P=1.3*10(-5)), impaired cardiac function (maximum ventricular
      power, P=0.0002), and increased ventricular dilation (end-diastolic volume,
      P=0.01). The rST2 treatment prevented eosinophilia and improved heart function
      compared with rIL-33 treatment (ejection fraction, P=0.009). Neither treatment
      altered viral replication. The rIL-33 treatment increased IL-4, IL-33, IL-1beta,
      and IL-6 levels in the heart during acute myocarditis. To determine whether IL-33
      altered cardiac function on its own, we administered rIL-33 to undiseased mice
      and found that rIL-33 induced eosinophilic pericarditis and adversely affected
      heart function. We used cytokine knockout mice to determine that this effect was
      due to IL-33-mediated signaling but not to IL-1beta or IL-6. CONCLUSIONS: We show
      for the first time to our knowledge that IL-33 induces eosinophilic pericarditis,
      whereas soluble ST2 prevents eosinophilia and improves systolic function, and
      that IL-33 independently adversely affects heart function through the IL-33
      receptor.

PMID- 22454398
TI  - Definition of treatment response in rheumatoid arthritis based on the simplified
      and the clinical disease activity index.
AB  - BACKGROUND: The simplified disease activity index (SDAI) and the clinical disease
      activity index (CDAI) are established instruments to measure disease activity in
      rheumatoid arthritis (RA). To date, no validated response definitions for the
      SDAI and CDAI are available. OBJECTIVE: The authors aimed to define minor,
      moderate and major response criteria for the SDAI. METHODS: The authors used data
      from two clinical trials on infliximab versus methotrexate in early (ASPIRE) or
      established (ATTRACT) RA, and identified the three SDAI cutpoints based on the
      best agreement (by kappa statistics) with the American College of Rheumatology
      (ACR)20/50/70 responses. Cutpoints were then tested for different aspects of
      validity in the trial datasets and in a Norwegian disease modifying antirheumatic
      drug prescription dataset (NOR-DMARD). RESULTS: Based on agreement with the ACR
      response, the minor, moderate and major responses were identified as SDAI 50%,
      70% and 85% improvement. These cutpoints had good face validity concerning the
      disease activity states achieved by the different response definitions. Construct
      validity was shown by a clear association of increasing SDAI response categories
      with increasing levels of functional improvement, achievement of better
      functional states and lower annual radiographic progression. Across SDAI
      50/70/85, the sensitivities regarding a patient-perceived improvement decreased
      (73%/39%/22%) and the specificities increased (61%/89%/96%) in a meaningful way.
      Further, the cutpoints discriminated the different treatment arms in ASPIRE and
      ATTRACT. The same cutpoints were used for the CDAI, with similar results in the
      validation analyses. CONCLUSION: These new response criteria expand the
      usefulness of the SDAI and CDAI for their use as endpoints in clinical trials
      beyond the definition of disease activity categories.

PMID- 22454397
TI  - Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      affecting motor neurons. Mutations in related RNA-binding proteins TDP-43,
      FUS/TLS and TAF15 have been connected to ALS. These three proteins share several
      features, including the presence of a bioinformatics-predicted prion domain,
      aggregation-prone nature in vitro and in vivo and toxic effects when expressed in
      multiple model systems. Given these commonalities, we hypothesized that a related
      protein, EWSR1 (Ewing sarcoma breakpoint region 1), might also exhibit similar
      properties and therefore could contribute to disease. Here, we report an analysis
      of EWSR1 in multiple functional assays, including mutational screening in ALS
      patients and controls. We identified three missense variants in EWSR1 in ALS
      patients, which were absent in a large number of healthy control individuals. We
      show that disease-specific variants affect EWSR1 localization in motor neurons.
      We also provide multiple independent lines of in vitro and in vivo evidence that
      EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation
      prone behavior in vitro and ability to confer neurodegeneration in Drosophila.
      Postmortem analysis of sporadic ALS cases also revealed cytoplasmic
      mislocalization of EWSR1. Together, our studies highlight a potential role for
      EWSR1 in ALS, provide a collection of functional assays to be used to assess
      roles of additional RNA-binding proteins in disease and support an emerging
      concept that a class of aggregation-prone RNA-binding proteins might contribute
      broadly to ALS and related neurodegenerative diseases.

PMID- 22454400
TI  - The risk of metachronous cancers in patients with small-intestinal carcinoid
      tumors: a US population-based study.
AB  - Small-intestinal carcinoids (SIC) are the most common small-bowel malignancies.
      We sought to determine the risk of developing SIC before and after other primary
      malignancies (PM) and the prognosis of patients with SIC, with and without
      another PM. We used the Surveillance, Epidemiology, and End Results database to
      identify patients diagnosed with SICs between 1973 and 2007. Multiple primary
      standardized incidence ratios were calculated as an approximation of relative
      risk (RR) to explore the association of SICs with metachronous malignancies.
      Survival analysis was performed using Kaplan-Meier methods and Cox proportional
      hazard models. Among 8331 patients with SICs, 2424 (29%) had another PM at some
      time. The most common sites were prostate (26.2%), breast (14.3%), colon (9.1%),
      lung/bronchus (6.3%), and bladder (5.3%). Overall, 67% of patients had a PM
      diagnosed before SIC (pre-SIC), 33% after SIC (post-SIC), and 8% had a PM both
      before and after SIC. Among the pre-SIC group, the risk of future SIC was
      increased after cancers of the small bowel (RR 11.86 (95% CI: 6.13-20.72)),
      esophagus (4.05 (1.10-10.36)), colon (1.39 (1.05-1.81)), kidney (1.93 (1.12
      3.09)), prostate (1.38 (1.17-1.62)), and leukemia (2.15 (1.18-3.61)). Among the
      post-SIC group, there was an increased risk of future PM of the small bowel (8.78
      (4.54-15.34)), liver (2.49 (1.08-4.91)), prostate (1.25 (1.0-1.53)), and thyroid
      (2.73 (1.10-5.62)). Compared to patients with only SIC, those with a PM pre-SIC
      had worse mean survival (57.9 vs 40.9 months, HR 1.55 (1.42-1.69), P<0.001). In
      conclusion, almost one-third of patients with SICs have an associated
      metachronous primary tumor. When these primaries occur prior to (but not after)
      the SIC diagnosis, the prognosis is worse than with an initial SIC. The type of
      malignancies associated with SICs may guide future screening efforts.

PMID- 22454399
TI  - Genetic characterization of large parathyroid adenomas.
AB  - In this study, we genetically characterized parathyroid adenomas with large
      glandular weights, for which independent observations suggest pronounced clinical
      manifestations. Large parathyroid adenomas (LPTAs) were defined as the 5% largest
      sporadic parathyroid adenomas identified among the 590 cases operated in our
      institution during 2005-2009. The LPTA group showed a higher relative number of
      male cases and significantly higher levels of total plasma and ionized serum
      calcium (P<0.001). Further analysis of 21 LPTAs revealed low MIB1 proliferation
      index (0.1-1.5%), MEN1 mutations in five cases, and one HRPT2 (CDC73) mutation.
      Total or partial loss of parafibromin expression was observed in ten tumors, two
      of which also showed loss of APC expression. Using array CGH, we demonstrated
      recurrent copy number alterations most frequently involving loss in 1p (29%),
      gain in 5 (38%), and loss in 11q (33%). Totally, 21 minimal overlapping regions
      were defined for losses in 1p, 7q, 9p, 11, and 15q and gains in 3q, 5, 7p, 8p,
      16q, 17p, and 19q. In addition, 12 tumors showed gross alterations of entire or
      almost entire chromosomes most frequently gain of 5 and loss of chromosome 11.
      While gain of 5 was the most frequent alteration observed in LPTAs, it was only
      detected in a small proportion (4/58 cases, 7%) of parathyroid adenomas. A
      significant positive correlation was observed between parathyroid hormone level
      and total copy number gain (r=0.48, P=0.031). These results support that LPTAs
      represent a group of patients with pronounced parathyroid hyperfunction and
      associated with specific genomic features.

PMID- 22454401
TI  - Novel candidate genes of thyroid tumourigenesis identified in Trk-T1 transgenic
      mice.
AB  - For an identification of novel candidate genes in thyroid tumourigenesis, we have
      investigated gene copy number changes in a Trk-T1 transgenic mouse model of
      thyroid neoplasia. For this aim, 30 thyroid tumours from Trk-T1 transgenics were
      investigated by comparative genomic hybridisation. Recurrent gene copy number
      alterations were identified and genes located in the altered chromosomal regions
      were analysed by Gene Ontology term enrichment analysis in order to reveal gene
      functions potentially associated with thyroid tumourigenesis. In thyroid
      neoplasms from Trk-T1 mice, a recurrent gain on chromosomal bands 1C4-E2.3 (10.0%
      of cases), and losses on 3H1-H3 (13.3%), 4D2.3-E2 (43.3%) and 14E4-E5 (6.7%) were
      identified. The genes Twist2, Ptma, Pde6d, Bmpr1b, Pdlim5, Unc5c, Srm, Trp73,
      Ythdf2, Taf12 and Slitrk5 are located in these chromosomal bands. Copy number
      changes of these genes were studied by fluorescence in situ hybridisation on 30
      human papillary thyroid carcinoma (PTC) samples and altered gene expression was
      studied by qRT-PCR analyses in 67 human PTC. Copy number gains were detected in
      83% of cases for TWIST2 and in 100% of cases for PTMA and PDE6D. DNA losses of
      SLITRK1 and SLITRK5 were observed in 21% of cases and of SLITRK6 in 16% of cases.
      Gene expression was significantly up-regulated for UNC5C and TP73 and
      significantly down-regulated for SLITRK5 in tumours compared with normal tissue.
      In conclusion, a global genomic copy number analysis of thyroid tumours from Trk
      T1 transgenic mice revealed a number of novel gene alterations in thyroid
      tumourigenesis that are also prevalent in human PTCs.

PMID- 22454402
TI  - Growth in a time of change.

PMID- 22454405
TI  - Self-monitoring of blood glucose is associated with problem-solving skills in
      hyperglycemia and hypoglycemia.
AB  - PURPOSE: The purpose of this study was to examine the association between self
      monitoring of blood glucose (SMBG) and problem-solving skills in response to
      detected hyperglycemia and hypoglycemia among patients with type 2 diabetes.
      METHODS: Data were obtained from the American Association of Diabetes Educators
      Outcome System, implemented in 8 diabetes self-management education programs in
      western Pennsylvania. SMBG was measured by asking patients how often they
      checked, missed checking, or checked blood glucose later than planned. Problem
      solving skill was measured by asking how often they modified their behaviors
      after detecting high or low blood glucose. RESULTS: Most patients checked their
      blood glucose at least once per day. However, when blood glucose was high or low,
      many of them reported doing nothing, and only some of them resolved the problem.
      There were significant associations between self-monitoring of blood glucose and
      problem-solving skills for hyperglycemia and hypoglycemia, after controlling for
      age, gender, ethnicity, education, and time since diagnosis. CONCLUSIONS:
      Patients reported poor problem-solving skills when detecting hyperglycemia and
      hypoglycemia via SMBG. Patients need to learn problem-solving skills along with
      SMBG training to achieve glycemic control.

PMID- 22454406
TI  - Lifestyle behaviors, chronic diseases, and ratings of health between black and
      white adults with pre-diabetes.
AB  - PURPOSES: The purposes of this study were to assess differences in lifestyle
      behaviors and other health-related factors between black and white adults with
      pre-diabetes and to identify predictors for lifestyle behaviors. METHODS: Using
      the 2007 and 2009 data from the Behavioral Risk Factor Surveillance System
      (BRFSS), an annual cross-sectional survey of randomly selected samples from each
      state, black (n = 1156) and white (n = 9539) adults with pre-diabetes were
      compared on lifestyle behaviors, general health practices, perceptions of health,
      chronic diseases, and access to care. Predictors for participating in regular
      physical activity and adequate intake of fruits and vegetables were identified
      for each racial and gender group using multiple regression procedures. RESULTS:
      Less than 40% of the adults with pre-diabetes participated in regular physical
      activity, and less than a quarter had adequate intake of fruits and vegetables;
      only 20% met the body weight recommendations. Compared to whites, blacks were
      more likely to be overweight/obese (86% vs 79%) and less likely to engage in
      regular physical activity (29% vs 40%). Except for adequate intake of fruits and
      vegetables, each racial and gender group had different predictors for regular
      physical activity. For black males, the predictors included impaired physical
      health and coronary heart disease/stroke. For black females, the predictors were
      younger age and routine checkup. CONCLUSIONS: Significant disparities exist
      between blacks and whites in lifestyle behaviors and other health-related
      factors. Targeted intervention strategies are needed to motivate blacks to modify
      behaviors to prevent or delay the development of diabetes.

PMID- 22454407
TI  - Physical activity-related experiences, counseling expectations, personal
      responsibility, and altruism among urban African American women with type 2
      diabetes.
AB  - PURPOSE: The purpose of this study was to explore physical activity-related
      experiences, perceptions, and counseling expectations among urban, underactive,
      African American women with type 2 diabetes. METHODS: Participants were recruited
      via flyers and endocrinologist referral. A professional, African American female
      moderator led 2 focus groups among 11 participants. Focus groups were conducted
      in a video- and audio-equipped focus group room in the evening hours. Using a
      content-based, stepped analytic approach, 2 raters independently analyzed data
      and collaborated to compare results and finalize themes. RESULTS: Competing
      priorities and lack of motivation were perceived as significant barriers to
      physical activity. Physical activity-related counseling expectations (ie,
      physician encouragement) and experiences (physician advising) were inconsistent.
      Participants expressed a high degree of physical activity-related health
      responsibility. Altruistic intentions were high relative to helping others
      incorporate healthful lifestyle changes. CONCLUSIONS: When counseling women about
      physical activity, diabetes educators should acknowledge and provide support and
      resources to help women incorporate more physical activity into their regular
      routines and enhance motivation for physical activity. Educators should also
      couple physical activity-related advice with encouragement and support. Because
      of high levels of altruism, educators should consider implementing group- and/or
      peer-based physical activity interventions in this patient group.

PMID- 22454408
TI  - Effects of food-related interventions for African American women with type 2
      diabetes.
AB  - PURPOSE: The purpose of this systematic review is to synthesize research that
      tested culturally competent food-related interventions designed for African
      American women with type 2 diabetes, to review the current state of the
      literature and suggest recommendations for future research. Many African American
      women with type 2 diabetes are challenged to change their culturally rooted food
      habits to achieve diabetes control. Diabetes educators and clinicians who work
      with African American women need knowledge of effective interventions to assist
      their clients. METHODS: Online databases and research articles' reference lists
      were searched for relevant studies published from 1989 to 2010 that tested
      culturally competent type 2 diabetes management interventions for African
      American women, that included at least 1 educational session on diet or
      nutrition, and that addressed a physiologic outcome, such as glycosylated
      hemoglobin or fasting blood glucose. RESULTS: Fifteen studies met the inclusion
      criteria for this review. Among them, 64% to 100% of the participants were
      African Americans, and 65% to 100% were women. Six studies showed significant
      improvements in food practices, and 8 showed significant improvements in glycemic
      control as a result of the interventions. CONCLUSIONS: Few studies focused solely
      on helping African American women make culturally relevant dietary changes to
      control type 2 diabetes. Most interventions addressed food habits as one of many
      components for diabetes control, perhaps overwhelming research participants with
      large amounts of varied information. Targeted interventions are recommended that
      focus on dietary changes as the foundation for diabetes self-management education
      for African American women.

PMID- 22454410
TI  - Atrial lead placement at the lower atrial septum: a potential strategy to reduce
      unnecessary right ventricular pacing.
AB  - AIMS: Right ventricular (RV) pacing has been shown to be potentially detrimental
      to left ventricular function. In conventional dual-chamber pacing the position of
      the atrial lead could influence duration of the atrio-ventricular (AV) intervals,
      which is one of the variables that could be associated with an increased
      percentage of RV pacing. We wanted to see if lead placement at selected atrial
      septal sites could reduce AV intervals in patients receiving a dual-chamber
      pacemaker or implantable cardioverter defibrillator. METHODS AND RESULTS: This
      was a prospective, acute, randomized single centre study that enrolled 57
      patients. The atrial lead was placed in both the right atrial appendage (RAA) and
      the lower atrial septum (LAS) in each patient in random order. The P-wave
      durations, PR intervals, A sense-V sense (As-Vs), and A pace-V sense (Ap-Vs)
      intervals were measured at both atrial lead locations in each patient during
      device implant. The P-wave durations during sinus rhythm (SR), RAA pacing, and
      LAS pacing were 113 +/- 19, 144 +/- 27, and 84 +/- 12 ms (RAA vs. LAS, P <
      0.001), respectively. The PR intervals during SR, RAA pacing, and LAS pacing were
      195 +/- 47, 230 +/- 61, and 167 +/- 44 ms (RAA vs. LAS, P < 0.001), respectively.
      The As-Vs interval was 31% shorter in LAS pacing than in RAA pacing (134 +/- 44
      ms vs. 194 +/- 52 ms, P < 0.001). The Ap-Vs interval was 24% shorter during LAS
      pacing than during RAA pacing (195 +/- 45 ms vs. 257 +/- 63 ms, P < 0.001).
      CONCLUSION: When compared with RAA pacing, LAS pacing was associated with a
      shorter P wave duration, PR interval, As-Vs, and Ap-Vs intervals. The potential
      long-term impact of the strategy of pacing from LAS in reducing unnecessary RV
      pacing needs to be explored in future studies.

PMID- 22454409
TI  - Angiotensin II-mediated up-regulation of connective tissue growth factor promotes
      atrial tissue fibrosis in the canine atrial fibrillation model.
AB  - AIMS: Remodelling of the extracellular matrix (ECM) plays an important role in
      the production of arrhythmogenic substrate for atrial fibrillation (AF), and is
      considered to be promoted by the connective tissue growth factor (CTGF). Our
      objective was to assess the relationship between CTGF and ECM synthesis, and the
      effect of olmesartan on these processes. METHODS AND RESULTS: Fifteen canine AF
      models were produced by rapid atrial stimulation. They were divided into three
      groups: pacing control (n = 5): 6-week pacing, pacing + olmesartan (n = 5):
      pacing with olmesartan (2 mg/kg/day), and non-pacing group (n = 5). In the pacing
      control group, messenger ribonucleic acid expressions of CTGF and collagen types
      1 and 3 were up-regulated in comparison with the non-pacing group (P < 0.05)
      while transforming growth factor-beta (TGF-beta) did not exhibit a significant
      difference. In the pacing + olmesartan group, these up-regulations were
      suppressed (P < 0.05). In fluorescent immunostaining, the expression of CTGF was
      localized in the cytoplasm. The protein level of collagen type 3 was increased in
      the pacing control and it was suppressed in the pacing + olmesartan group.
      CONCLUSIONS: CTGF and associated genes were up-regulated in the atria with the
      appearance of fibrosis. Because this up-regulation was independent of TGF-beta
      and suppressed by olmesartan, CTGF up-regulation was considered to be mediated by
      angiotensin II.

PMID- 22454411
TI  - A risk on an unprecedented scale in pacemaker implantation: prolonged waiting
      periods for urgent pacing indications.

PMID- 22454412
TI  - Funding oncology clinical trials: are cooperative group trials sustainable?
AB  - PURPOSE: Many oncology clinical trials departments (CTDs) are in serious fiscal
      deficit and their sustainability is in jeopardy. This study investigates whether
      the payment models used to fund industry versus cooperative group trials
      contribute to the fiscal deficit of a CTD. METHODS: We examined the lifetime
      costs of all cooperative group and industry trials activated in the CTD of a
      cancer center between 2007 and 2011. A trial's lifetime is defined as being from
      the date the first patient was accrued until the last patient's actual or
      projected final follow-up visit. For each trial, we calculated the lifetime
      monthly net income, which was defined as monthly revenue minus monthly costs.
      Data sources included study protocols, trial budgets, and accrual data. RESULTS:
      Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of
      lifetime net income for cooperative group trials has a positive peak during
      patient accrual followed by a negative trough during follow-up. In contrast, the
      pattern for industry trials resembled an "l" shape. The patterns reflect the
      differing payment models: upfront lump-sum payments (cooperative group) versus
      milestone payments (industry). CONCLUSION: The negative trough in the lifetime
      net income of a cooperative group trial occurs because follow-up costs are
      typically not funded or are underfunded. CTDs accrue more patients in new trials
      to offset that deficit. The CTD uses revenue from accrual to existing trials to
      cross-subsidize past trials in follow-up. As the number of patients on follow-up
      increases, the fiscal deficit grows larger each year, perpetuating the cycle.

PMID- 22454413
TI  - PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in
      rhabdomyosarcoma and significantly improves current risk stratification.
AB  - PURPOSE: To improve the risk stratification of patients with rhabdomyosarcoma
      (RMS) through the use of clinical and molecular biologic data. PATIENTS AND
      METHODS: Two independent data sets of gene-expression profiling for 124 and 101
      patients with RMS were used to derive prognostic gene signatures by using a meta
      analysis. These and a previously published metagene signature were evaluated by
      using cross validation analyses. A combined clinical and molecular risk
      stratification scheme that incorporated the PAX3/FOXO1 fusion gene status was
      derived from 287 patients with RMS and evaluated. RESULTS: We showed that our
      prognostic gene-expression signature and the one previously published performed
      well with reproducible and significant effects. However, their effect was reduced
      when cross validated or tested in independent data and did not add new prognostic
      information over the fusion gene status, which is simpler to assay. Among
      nonmetastatic patients, patients who were PAX3/FOXO1 positive had a significantly
      poorer outcome compared with both alveolar-negative and PAX7/FOXO1-positive
      patients. Furthermore, a new clinicomolecular risk score that incorporated fusion
      gene status (negative and PAX3/FOXO1 and PAX7/FOXO1 positive), Intergroup
      Rhabdomyosarcoma Study TNM stage, and age showed a significant increase in
      performance over the current risk-stratification scheme. CONCLUSION: Gene
      signatures can improve current stratification of patients with RMS but will
      require complex assays to be developed and extensive validation before clinical
      application. A significant majority of their prognostic value was encapsulated by
      the fusion gene status. A continuous risk score derived from the combination of
      clinical parameters with the presence or absence of PAX3/FOXO1 represents a
      robust approach to improving current risk-adapted therapy for RMS.

PMID- 22454414
TI  - Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel
      and prednisone with or without bevacizumab in men with metastatic castration
      resistant prostate cancer: CALGB 90401.
AB  - PURPOSE: A randomized, placebo-controlled study based on preclinical and clinical
      data that supports the potential role of vascular endothelial growth factor in
      prostate cancer was performed to evaluate the addition of bevacizumab to standard
      docetaxel and prednisone therapy in patients with metastatic castration-resistant
      prostate cancer (mCRPC). PATIENTS AND METHODS: Patients with chemotherapy-naive
      progressive mCRPC with Eastern Cooperative Oncology Group performance status <= 2
      and adequate bone marrow, hepatic, and renal function were randomly assigned to
      receive docetaxel 75 mg/m(2) intravenously (IV) over 1 hour for 21 days plus
      prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV
      every 3 weeks (DP + B) or placebo. The primary end point was overall survival
      (OS), and secondary end points were progression-free survival (PFS), 50% decline
      in prostate-specific antigen, objective response (OR), and toxicity. RESULTS: In
      total, 1,050 patients were randomly assigned. The median OS for patients given DP
      + B was 22.6 months compared with 21.5 months for patients treated with DP
      (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The
      median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log
      rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P =
      .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B
      (75.4% v 56.2%; P <= .001), as was the number of treatment-related deaths (4.0% v
      1.2%; P = .005). CONCLUSION: Despite an improvement in PFS and OR, the addition
      of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC
      and was associated with greater toxicity.

PMID- 22454415
TI  - Marked, homogeneous, and early [18F]fluorodeoxyglucose-positron emission
      tomography responses to vemurafenib in BRAF-mutant advanced melanoma.
AB  - PURPOSE: Imaging with [(18)F]fluorodeoxyglucose (FDG) -positron emission
      tomography (PET) allows early recognition of a response to agents that target key
      driver mutations in human cancer. We aimed to determine the metabolic response
      rate to vemurafenib in patients with advanced BRAF-mutant melanoma. PATIENTS AND
      METHODS: Baseline and day 15 FDG-PET was evaluated in 31 patients with advanced
      melanoma treated in a phase I study of dose escalation of vemurafenib (PLX06-02),
      which included four patients treated at subtherapeutic doses and 24 patients
      treated at 960 mg twice a day, which is the maximum-tolerated dose of
      vemurafenib. RESULTS: All 27 patients treated at potentially therapeutic levels
      had at least a partial metabolic response, and three patients achieved a complete
      metabolic response. In the 27 patients, there was an 80% +/- 3% reduction in the
      maximum standardized uptake value (SUVmax) of target lesions and an 87% +/- 3%
      decrease in the percentage of injected dose (%ID) in all identified disease
      sites. There was a positive correlation between %ID in all identified disease and
      target-lesion SUVmax (r(2) = 0.66; P < .001) that indicated a significant
      homogeneity of the response between lesions in individual patients. Although no
      relationship was found between the reduction in target lesion SUVmax and best
      response according to RECIST (Response Evaluation Criteria in Solid Tumors),
      there was a trend for patients with greater reductions in uptake of FDG to have
      longer progression-free survival. CONCLUSION: FDG-PET is a useful marker of an
      early biologic response to vemurafenib. Little variability in PET response was
      found between lesions in individual patients, which suggested minimal
      intrapatient molecular heterogeneity. FDG-PET is a useful tool for the evaluation
      of the biologic impact of inhibiting mutant BRAF and may allow for the more
      effective development of novel agents.

PMID- 22454416
TI  - Early [18F]fluorodeoxyglucose-positron emission tomography responses in
      metastatic melanoma: what do they mean?

PMID- 22454417
TI  - Dissecting the heterogeneity of triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers.
      It is a heterogeneous disease, not only on the molecular level, but also on the
      pathologic and clinical levels. TNBC is associated with a significantly higher
      probability of relapse and poorer overall survival in the first few years after
      diagnosis when compared with other breast cancer subtypes. This is observed
      despite its usual high sensitivity to chemotherapy. In the advanced setting,
      responses observed with chemotherapy lack durability. Early-stage clinical
      studies suggested impressive potential when a poly (ADP-ribose) polymerase (PARP)
      inhibitor is given for the treatment of advanced TNBC with BRCA gene dysfunction.
      The molecular complexity of TNBC has led to proposed subclassifications, which
      will be of great value for the development of targeted therapies. In this review,
      we discuss the biology of TNBC at the pathologic and the molecular levels. We
      also elaborate on the role of systemic therapies and the results of the first
      phase III clinical trial evaluating the addition of iniparib, a novel
      investigational anticancer agent that does not possess characteristics typical of
      the PARP inhibitor class, in combination with chemotherapy in advanced TNBC.

PMID- 22454418
TI  - Relationship between deficits in overall quality of life and non-small-cell lung
      cancer survival.
AB  - PURPOSE: Evidence has suggested a clinically meaningful relationship between self
      reported quality of life (QOL) of a patient with cancer at the time of receiving
      a cancer diagnosis and overall survival (OS). This study evaluated the prognostic
      value of QOL assessments with regard to OS in a large cohort of patients with
      lung cancer. PATIENTS AND METHODS: A total of 2,442 patients with non-small-cell
      lung cancer were observed between 1997 and 2007 and completed a single-item
      measure of overall QOL within the first 6 months of receiving a lung cancer
      diagnosis; these were dichotomized using an a priori definition of a clinically
      deficient score (CDS; <= 50 v > 50). Kaplan-Meier estimates and Cox models were
      used to evaluate the prognostic importance of QOL on OS alone and in the presence
      of covariates. Logistic regression modeling was used to identify which clinical
      and patient characteristics were related to a clinically meaningful deficit in
      QOL. RESULTS: QOL deficits at time of lung cancer diagnosis were significantly
      associated with OS (hazard ratio [HR], 1.55; P < .001), as were performance
      status, older age, smoking history, male sex, treatment factors, and stage of
      disease. The median survival for patients with CDS QOL was 1.6 years versus 5.6
      years for patients with non-CDS QOL. After controlling for all these covariates,
      the indication of a clinically deficient baseline QOL still contributed
      significantly to the prediction of patient survival (HR, 0.67; P < .001).
      CONCLUSION: Overall QOL measured by a simple single item at the time of lung
      cancer diagnosis is a significant and independent prognostic factor for survival
      in patients with lung cancer.

PMID- 22454419
TI  - Underestimating cardiac toxicity in cancer trials: lessons learned?

PMID- 22454420
TI  - Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF
      00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors.
AB  - PURPOSE: PF-00562271 is a novel inhibitor of focal adhesion kinase (FAK). The
      objectives of this study were to identify the recommended phase II dose (RP2D)
      and assess safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD),
      and antitumor activity of PF-00562271. PATIENTS AND METHODS: Part 1 was a dose
      escalation without and with food. Part 2 enrolled specific tumor types in an
      expansion at the RP2D and also assessed the effect of PF-00562271 on single-dose
      midazolam PK in a subgroup of patients. RESULTS: Ninety-nine patients (median
      age, 60 years; 98% with Eastern Cooperative Oncology Group performance status of
      0 or 1) were treated in 12 fasting and three fed cohorts. The 125-mg twice-per
      day fed dose was deemed the maximum-tolerated dose (MTD) and RP2D. Grade 3 dose
      limiting toxicities included headache, nausea/vomiting, dehydration, and edema.
      Nausea was the most frequently observed toxicity (60% of patients, all grades 1
      or 2 at RP2D). PF-00562271 exposure increased with increasing dose; serum
      concentration-time profiles showed characteristic nonlinear disposition. Steady
      state exposures were reached within 1 week. On coadministration, geometric mean
      values of midazolam maximal observed serum concentration and area under the serum
      concentration-time curve increased by 60% and more than two-fold, respectively.
      Of 14 patients evaluable by [(18)F]fluorodeoxyglucose positron emission
      tomography in the expansion cohorts, seven metabolic responses were observed.
      With conventional imaging, 31 patients had stable disease at first restaging
      scans, and 15 of these remained stable for six or more cycles. CONCLUSION: The
      MTD and RP2D of PF-00562271 is 125 mg twice per day with food. PF-00562271
      displayed time- and dose-dependent nonlinear PK and is likely a potent CYP 3A
      inhibitor. This first-in-class study supports further investigation of FAK as a
      promising therapeutic target.

PMID- 22454421
TI  - Results of a pivotal phase II study of brentuximab vedotin for patients with
      relapsed or refractory Hodgkin's lymphoma.
AB  - PURPOSE: Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively
      delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing
      cells. In phase I studies, brentuximab vedotin demonstrated significant activity
      with a favorable safety profile in patients with relapsed or refractory CD30
      positive lymphomas. PATIENTS AND METHODS: In this multinational, open-label,
      phase II study, the efficacy and safety of brentuximab vedotin were evaluated in
      patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous
      stem-cell transplantation (auto-SCT). Patients had histologically documented CD30
      positive HL by central pathology review. A total of 102 patients were treated
      with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the
      absence of disease progression or prohibitive toxicity, patients received a
      maximum of 16 cycles. The primary end point was the overall objective response
      rate (ORR) determined by an independent radiology review facility. RESULTS: The
      ORR was 75% with complete remission (CR) in 34% of patients. The median
      progression-free survival time for all patients was 5.6 months, and the median
      duration of response for those in CR was 20.5 months. After a median observation
      time of more than 1.5 years, 31 patients were alive and free of documented
      progressive disease. The most common treatment-related adverse events were
      peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea.
      CONCLUSION: The ADC brentuximab vedotin was associated with manageable toxicity
      and induced objective responses in 75% of patients with relapsed or refractory HL
      after auto-SCT. Durable CRs approaching 2 years were observed, supporting study
      in earlier lines of therapy.

PMID- 22454422
TI  - Robbing peter to pay paul: financing clinical trial follow-up.

PMID- 22454423
TI  - Genetic variations and patient-reported quality of life among patients with lung
      cancer.
AB  - PURPOSE: Recent evidence has suggested a relationship between the baseline
      quality of life (QOL) self-reported by patients with cancer and genetic
      disposition. We report an analysis exploring relationships among baseline QOL
      assessments and candidate genetic variations in a large cohort of patients with
      lung cancer. PATIENTS AND METHODS: QOL data were provided by 1,299 patients with
      non-small-cell lung cancer observed at the Mayo Clinic between 1997 and 2007.
      Overall QOL and subdomains were assessed by either Lung Cancer Symptom Scale or
      Linear Analog Self Assessment measures; scores were transformed to a scale of 0
      to 10, with higher scores representing better status. Baseline QOL scores
      assessed within 1 year of diagnosis were dichotomized as clinically deficient
      (CD) or not. A total of 470 single nucleotide polymorphisms (SNPs) in 56 genes of
      three biologic pathways were assessed for association with QOL measures. Logistic
      regression with training/validation samples was used to test the association of
      SNPs with CD QOL. RESULTS: Six SNPs on four genes were replicated using our split
      schemes. Three SNPs in the MGMT gene (adjusted analysis, rs3858300; unadjusted
      analysis, rs10741191 and rs3852507) from DNA repair pathway were associated with
      overall QOL. Two SNPs (rs2287396 [GSTZ1] and rs9524885 [ABCC4]) from glutathione
      metabolic pathway were associated with fatigue in unadjusted analysis. In
      adjusted analysis, two SNPs (rs2756109 [ABCC2] and rs9524885 [ABCC4]) from
      glutathione metabolic pathway were associated with pain. CONCLUSION: We
      identified three SNPs in three glutathione metabolic pathway genes and three SNPs
      in two DNA repair pathway genes associated with QOL measures in patients with non
      small-cell lung cancer.

PMID- 22454424
TI  - Impact of age and comorbidity on non-small-cell lung cancer treatment in older
      veterans.
AB  - PURPOSE: Because comorbidity affects cancer treatment outcomes, guidelines
      recommend considering comorbidity when making treatment decisions in older
      patients with lung cancer. Yet, it is unclear whether treatment is targeted to
      healthier older adults who might reasonably benefit. PATIENTS AND METHODS:
      Receipt of first-line guideline-recommended treatment was assessed for 20,511
      veterans age >= 65 years with non-small-cell lung cancer (NSCLC) in the Veterans
      Affairs (VA) Central Cancer Registry from 2003 to 2008. Patients were stratified
      by age (65 to 74, 75 to 84, >= 85 years), Charlson comorbidity index score (0, 1
      to 3, >= 4), and American Joint Committee on Cancer stage (I to II, IIIA to IIIB,
      IIIB with malignant effusion to IV). Comorbidity and patient characteristics were
      obtained from VA claims and registry data. Multivariate analysis identified
      predictors of receipt of guideline-recommended treatment. RESULTS: In all, 51% of
      patients with local, 35% with regional, and 27% with metastatic disease received
      guideline-recommended treatment. Treatment rates decreased more with advancing
      age than with worsening comorbidity for all stages, such that older patients with
      no comorbidity had lower rates than younger patients with severe comorbidity. For
      example, 50% of patients with local disease age 75 to 84 years with no
      comorbidity received surgery compared with 57% of patients age 65 to 74 years
      with severe comorbidity (P < .001). In multivariate analysis, age and histology
      remained strong negative predictors of treatment for all stages, whereas
      comorbidity and nonclinical factors had a minor effect. CONCLUSION: Advancing age
      is a much stronger negative predictor of treatment receipt among older veterans
      with NSCLC than comorbidity. Individualized decisions that go beyond age and
      include comorbidity are needed to better target NSCLC treatments to older
      patients who may reasonably benefit.

PMID- 22454426
TI  - Progress for stroke prevention with atrial fibrillation: emergence of alternative
      oral anticoagulants.

PMID- 22454429
TI  - The activation of DNA damage detection and repair responses in cleavage-stage rat
      embryos by a damaged paternal genome.
AB  - Male germ cell DNA damage, after exposure to radiation, exogenous chemicals, or
      chemotherapeutic agents, is a major cause of male infertility. DNA-damaged
      spermatozoa can fertilize oocytes; this is of concern because there is limited
      information on the capacity of early embryos to repair a damaged male genome or
      on the fate of these embryos if repair is inadequate. We hypothesized that the
      early activation of DNA damage response in the early embryo is a critical
      determinant of its fate. The objective of this study was to assess the DNA damage
      response and mitochondrial function as a measure of the energy supply for DNA
      repair and general health in cleavage-stage embryos sired by males chronically
      exposed to an anticancer alkylating agent, cyclophosphamide. Male rats were
      treated with saline or cyclophosphamide (6 mg/kg/day) for 4 weeks and mated to
      naturally cycling females. Pronuclear two- and eight-cell embryos were collected
      for immunofluorescence analysis of mitochondrial function and biomarkers of the
      DNA damage response: gammaH2AX foci, 53BP1 reactivity, and poly(ADP-ribose)
      polymer formation. Mitochondrial activities did not differ between embryos sired
      by control- and cyclophosphamide-exposed males. At the two-cell stage, there was
      no treatment-related increase in DNA double-strand breaks; by the eight-cell
      stage, a significant increase was noted, as indicated by increased medium and
      large gammaH2AX foci. This was accompanied by a dampened DNA repair response,
      detected as a decrease in the nuclear intensity of poly(ADP-ribose) polymers. The
      micronuclei formed in cyclophosphamide-sired embryos contained large gammaH2AX
      foci and enhanced poly(ADP-ribose) polymer and 53BP1 reactivity compared with
      their nuclear counterparts. Thus, paternal cyclophosphamide exposure activated a
      DNA damage response in cleavage-stage embryos. Furthermore, this damage response
      may be useful in assessing embryo quality and developmental competence.

PMID- 22454430
TI  - RNA-Seq reveals different mRNA abundance of transporters and their alternative
      transcript isoforms during liver development.
AB  - During development, the maturation of liver transporters is essential for
      chemical elimination in newborns and children. One cannot compare the real
      abundance of transcripts by conventional messenger RNA (mRNA) profiling methods;
      in comparison, RNA-Seq provides a "true quantification" of transcript counts and
      an unbiased detection of novel transcripts. The purpose of this study was to
      compare the mRNA abundance of liver transporters and seek their novel transcripts
      during liver development. Livers from male C57BL/6J mice were collected at 12
      ages from prenatal to adulthood. The transcriptome was determined by RNA-Seq,
      with transcript abundance estimated by Cufflinks. Among 498 known transporters,
      the ontogeny of 62 known critical xenobiotic transporters was examined in detail.
      The cumulative mRNAs of the uptake transporters increased more than the efflux
      transporters in livers after birth. A heatmap revealed three ontogenic patterns
      of these transporters, namely perinatal (reaching maximal expression before
      birth), adolescent (about 20 days), and adult enriched (about 60 days of age).
      Before birth, equilibrative nucleoside transporter 1 was the transporter with
      highest expression in liver (29%), followed by breast cancer resistance protein
      (Bcrp) (26%). Within 1 day after birth, the mRNAs of these two transporters
      decreased markedly, and Ntcp became the transporter with highest expression
      (52%). In adult liver, the transporters with highest expression were organic
      cation transporter 1 and Ntcp (23% and 22%, respectively). Three isoforms of Bcrp
      with alternate leading exons were identified (E1a, E1b, and E1c), with E1b being
      the major isoform. In conclusion, this study reveals the mRNA abundance of
      transporters in liver and demonstrates that the expression of liver transporters
      is both age and isoform specific.

PMID- 22454431
TI  - JAK/STAT pathway plays a critical role in the proinflammatory gene expression and
      apoptosis of RAW264.7 cells induced by trichothecenes as DON and T-2 toxin.
AB  - Deoxynivalenol (DON) and T-2 toxin commonly affect cells of the immune system and
      cause inflammation and apoptosis. Janus kinase/signal transducers and activators
      of transcription (JAK/STAT) pathway is highly associated with inflammatory
      process and apoptosis and is worth investigating its role when cells were exposed
      to trichothecenes. The results showed that DON and T-2 upregulated the messenger
      RNA (mRNA) expressions of interleukin (IL)-6, IL-1beta, tumor necrosis factor
      alpha, JAK1-2, STAT1-3, and suppressors of cytokine signaling members and
      activated the tyrosine phosphorylation of STAT1 and STAT3 with a dose-dependent
      manner in RAW264.7 cells. AG490 and Stattic, the specific inhibitors of JAK/STAT
      pathway, blocked the STAT1 and STAT3 tyrosine phosphorylation and decreased the
      gene expressions of proinflammatory cytokines induced by trichothecenes.
      Interestingly, the time when the mRNA levels of STAT1 and STAT3 were
      significantly upregulated was at 12 h, which was much later than the time when
      mitogen-activated protein kinase was activated, indicating that STATs might be
      the downstream targets of the trichothecenes. With the intervention of AG490 and
      Stattic, DON and T-2 toxin induced apoptosis in a strengthened way, with the loss
      of mitochondrial membrane potential and the decrease ratios of the B-cell
      leukemia/lymphoma 2 (Bcl-2)/bcl-2-associated X (Bax) and B-cell lymphoma-extra
      large (Bcl-xL)/Bax. After exposing to DON and T-2 toxin, cells exhibited G2/M and
      G0/G1 phase arrest, respectively. The increased mRNA expressions of STAT target
      genes p21 and cyclin D1 for DON and the increases in p21 mRNA and the decreases
      in cyclin D1 for T-2 toxin were observed. These results demonstrated for the
      first time that the activation of JAK/STAT might be a critical mediator to induce
      the inflammatory response and apoptosis in macrophage in response to
      trichothecenes.

PMID- 22454432
TI  - Determination of drug toxicity using 3D spheroids constructed from an immortal
      human hepatocyte cell line.
AB  - Numerous publications have documented that the immortal cells grown in three
      dimensional (3D) cultures possess physiological behavior, which is more
      reminiscent of their parental organ than when the same cells are cultivated using
      classical two-dimensional (2D) culture techniques. The goal of this study was to
      investigate whether this observation could be extended to the determination of
      LD(50) values and whether 3D data could be correlated to in vivo observations. We
      developed a noninvasive means to estimate the amount of protein present in a 3D
      spheroid from it is planar area (+/- 21%) so that a precise dose can be provided
      in a manner similar to in vivo studies. This avoided correction of the actual
      dose given based on a protein determination after treatment (when some cells may
      have lysed). Conversion of published in vitro LC(50) data (mM) for six common
      drugs (acetaminophen, amiodarone, diclofenac, metformin, phenformin, and valproic
      acid) to LD(50) data (mg compound/mg cellular protein) showed that the variation
      in LD(50) values was generally less than that suggested by the original LC(50)
      data. Toxicological analysis of these six compounds in 3D spheroid culture
      (either published or presented here) demonstrated similar LD(50) values. Although
      in vitro 2D HepG2 data showed a poor correlation, the primary hepatocyte and 3D
      spheroid data resulted in a much higher degree of correlation with in vivo lethal
      blood plasma levels. These results corroborate that 3D hepatocyte cultures are
      significantly different from 2D cultures and are more representative of the liver
      in vivo.

PMID- 22454438
TI  - Associations between self-rated health with cardiorespiratory fitness and obesity
      status among adolescent girls.
AB  - BACKGROUND: The main goal of this study was to analyze the associations between
      cardiorespiratory fitness (CRF) and body mass index (BMI) with self-rated health
      (SRH) of adolescent girls. METHODS: This was a cross-sectional study of 533
      adolescents girls, aged from 10 to 18 years old. CRF was predicted by maximal
      multistage 20-m shuttle-run test according to procedures described from
      FITNESSGRAM. Girls' obesity status was classified according to International
      Obesity Task Force and Self-rated health (SRH) was assessed by questionnaire.
      RESULTS: The findings showed that among adolescent girls 23.2% had negative SRH.
      Girls who were classified as unfit were more likely to report negative SRH in
      both univariate logistic (OR: 3.05; CI: 1.91-4.87; P < .05) and multivariate (OR:
      2.93; CI: 1.82-4.72; P < .05) regression analyses compared with their fit peers.
      Obese girls were more likely to report negative SRH (OR: 2.30; CI: 1.14-4.62; P <
      .05) compared with their normal-weight counterparts. However such association was
      lost in multivariate analyses suggesting an effect of CRF. CONCLUSIONS: Negative
      perception of health was associated with lower CRF and weight status although
      such association it is mediated by CRF condition.

PMID- 22454434
TI  - Correlates of physical activity at two time points during pregnancy.
AB  - BACKGROUND: Correlates of prenatal physical activity can inform interventions,
      but are not well-understood. METHODS: Participants in the Pregnancy, Infection,
      and Nutrition 3 Study were recruited before 20 weeks gestation. Women self
      reported frequency, duration, and mode of moderate and vigorous physical
      activities. We used logistic regression to identify correlates of any physical
      activity (>=10 minutes/week of any mode), any recreational activity (>=10
      minutes/week), and high volume recreational activity (either >=150 minutes/week
      of moderate or >=75 minutes/week of vigorous). Our analysis included 1752 women
      at 19-weeks gestation and 1722 at 29 weeks. RESULTS: Higher education, white
      race, and enjoyment of physical activity were positively correlated with all 3
      outcomes. Any recreational activity was negatively associated with parity, body
      mass index, and history of miscarriage. The associations of history of
      miscarriage and body mass index differed at 19 weeks compared with 29 weeks.
      Single marital status, health professional physical activity advice, and time for
      activity were associated with high volume recreational activity only.
      CONCLUSIONS: Correlates of physical activity differed by mode and volume of
      activity and by gestational age. This suggests that researchers planning physical
      activity interventions should consider the mode and amount of activity and the
      gestational age of the participants.

PMID- 22454440
TI  - Validity and comparability of a wrist-worn accelerometer in children.
AB  - BACKGROUND: Wrist-worn accelerometers may provide an alternative to hip-worn
      monitors for assessing physical activity as they are easier to wear and may thus
      facilitate long-term recordings. The current study aimed at a) assessing the
      validity of the Actiwatch (wrist-worn) for estimating energy expenditure, b)
      determining cut-off values for light, moderate, and vigorous activities, c)
      studying the comparability between the Actiwatch and the Actigraph (hip-worn),
      and d) assessing reliability. METHODS: For validity, indirect calorimetry was
      used as criterion measure. ROC-analyses were applied to identify cut-off values.
      Comparability was tested by simultaneously wearing of the 2 accelerometers during
      free-living condition. Reliability was tested in a mechanical shaker. RESULTS:
      All-over correlation between accelerometer output and energy expenditure were
      found to be 0.80 (P < .001).Based on ROC-analysis, cut-off values for 1.5, 3, and
      6 METs were found to be 80, 262, and 406 counts per 15 s, respectively. Energy
      expenditure estimates differed between the Actiwatch and the Actigraph (P < .05).
      The intra- and interinstrument coefficient of variation of the Actiwatch ranged
      between 0.72% and 8.4%. CONCLUSION: The wrist-worn Actiwatch appears to be valid
      and reliable for estimating energy expenditure and physical activity intensity in
      children aged 8 to 10 years.

PMID- 22454442
TI  - Virtual umra: an interdisciplinary faith-based pedometer intervention for
      increasing steps at school.
AB  - BACKGROUND: Curriculum interventions aimed at increasing physical activity in
      schools may prove useful in contexts where changes in policy/environment are not
      feasible. Design/evaluation of interventions targeting minority groups is
      important in light of well-publicized health disparities. Religious minorities
      represent a special subset that may positively respond to interventions tailored
      to their unique beliefs, which to date have been relatively underreported.
      METHODS: Muslim American youth (n = 45) attending a parochial middle school
      participated in a religiously- and culturally-tailored 8-wk, interdisciplinary
      pedometer intervention. School-time ambulatory activity was quantified using a
      delayed multiple-baseline across subjects ABA design. Visual analysis of graphic
      data as well as repeated-measures ANOVA and ANCOVA and post hoc contrasts were
      used to analyze step counts including the moderating effects of day type (PE, no
      PE), gender, BMI classification, grade, and time. RESULTS: The intervention
      elicited modest increases in males' steps only with effect decay beginning
      midintervention. BMI classification and grade were not associated with changes in
      steps. CONCLUSIONS: Full curricular integration by affected classroom teachers,
      staff modeling of PA behavior, and alternative curriculum for girls' PE classes
      may further potentiate the intervention.

PMID- 22454446
TI  - Daptomycin experience in critical care patients: results from a registry.
AB  - BACKGROUND: Vancomycin is often the drug of choice in critically ill patients
      with gram-positive infections, although circumstances often prevent its use. In
      these situations, clinicians are frequently left with limited data regarding
      alternative agents. OBJECTIVE: To describe patients with reported sepsis
      receiving daptomycin in a critical care unit. METHODS: This multicenter,
      noncomparative, noninterventional study identified patients in critical care
      units, using the Cubicin Outcomes Registry and Experience (CORE) 2005-2009
      registry. A descriptive account of patient characteristics, infectious etiology,
      outcomes at the end of daptomycin therapy, and 30-day mortality is reported.
      Nonevaluable patients were excluded from the efficacy analysis but included in
      the safety analysis. RESULTS: We identified 128 patients, 98 (77%) of whom were
      evaluable for efficacy. Patient characteristics for the efficacy population were
      55 (56%) males, 30 (31%) aged 66 years or older, 38 (39%) had creatinine
      clearance less than 30 mL/min, and 27 (28%) were on dialysis. Common underlying
      diseases included acute or chronic renal failure 44 (45%), hypertension 40 (41%),
      and diabetes 27 (28%). Seventy-two (73%) patients were bacteremic. The most
      common pathogens found were methicillin-resistant Staphylococcus aureus (32%),
      vancomycin-resistant Enterococcus faecium (21%), and coagulase-negative
      staphylococci (20%). Prior to daptomycin, antibiotics were used in 84 (86%)
      patients, most commonly vancomycin (65/84; 77%). The median (range) initial
      daptomycin dose was 6 mg/kg (3-10) and duration of 10 days (1-58). Overall
      success rate was 70% (31% cured; 39% improved). Twelve adverse events possibly
      related to daptomycin were reported in 9 of 128 (7%) patients in the safety
      population; 4 of these in 4 (3%) patients were serious. The mortality rate within
      30 days of completing daptomycin was 42 of 128 (33%) patients. CONCLUSIONS: These
      data provide preliminary results on the use of daptomycin in critically ill
      patients with complicated conditions. Controlled studies are needed to best
      evaluate daptomycin use in these patients.

PMID- 22454447
TI  - Examining utilization of a natural medicine Web-based tool among non-primary care
      physicians, academic faculty, and nurses at one institution.
AB  - BACKGROUND: Consumer use of herbal and natural products (H/NP) is increasing, yet
      physicians may be unprepared to provide guidance because of lack of educational
      training. This knowledge deficit may place consumers at risk of adverse effects.
      We had previously evaluated the impact of a natural medicine Web-based resource
      on primary care providers at our institution. OBJECTIVES: To ascertain the value
      of an H/NP Web-based resource to non-primary care physicians, academic faculty,
      and nurses practicing within a hospital setting. METHODS: Non-primary care
      physicians, academic faculty, and nurses at our medical center were invited to
      complete an electronic survey 1 year after access to an H/NP clinical decision
      tool had been obtained. RESULTS: Survey responses were obtained from 226 of 2720
      (8%) individuals invited to participate. Overall, respondents indicated a
      relatively low comfort level (mean 3.5 [2.28] [SD] on a 10-point scale) in
      discussing H/NP prior to introduction of the electronic H/NP resource. Following
      a year-long trial subscription to an evidence-based H/NP electronic resource, 29%
      of physician and nurse survey respondents (60 of 207) reported use of the tool.
      These individuals ranked their comfort level with H/NP discussions at a 6.96
      [1.76] on a 10-point scale. Seventy-six percent of physicians (16 of 21) and 72%
      of nurses (28 of 39) who had used the tool indicated that because of the
      resource, they were more likely to ask patients about H/NP use when taking a drug
      history; 44% (23 of 52) had been able to intervene when a patient was using an
      H/NP deemed to be unsafe. CONCLUSIONS: Our results suggest that an evidence-based
      H/NP resource boosts physician and nursing comfort in discussing H/NP with
      patients and enables interventions to be made. Such H/NP clinical decision tools
      have potential to improve patient care.

PMID- 22454448
TI  - Utilization, spending, and price trends for benzodiazepines in the US Medicaid
      program: 1991-2009.
AB  - BACKGROUND: Although it is well-known that drug costs in the US have risen
      precipitously over the last 25 years, what is much less appreciated is how this
      rise in cost has occurred across so many seemingly distinct drug markets.
      OBJECTIVE: To describe trends in the utilization, spending, and average per
      prescription cost of benzodiazepines individually, in subgroups, and overall, in
      the Medicaid program. Medicaid has been the primary public payer for
      benzodiazepines over the past 2 decades. METHODS: A retrospective, descriptive
      analysis was performed for the years 1991-2009 using the publicly available
      national Summary Files from the Medicaid State Drug Utilization Data maintained
      by the Centers for Medicare & Medicaid Services. Quarterly prescription counts
      and reimbursement amounts were calculated for all benzodiazepines reimbursed by
      Medicaid. Average per-prescription spending as a proxy for drug price was found
      by dividing reimbursement by the number of prescriptions. RESULTS: Prescriptions
      for benzodiazepines among Medicaid beneficiaries increased from 8.0 million in
      1991 to 17.1 million in 2009. Expenditures rose from $131.6 million to $171.1
      million over the same time period. The average per-prescription price was a
      little over $10 in 2009. Whereas utilization of intermediate- and long-acting
      agents increased over time, prescriptions for short-acting drugs fell from 1.1
      million to 0.3 million (1991-2009). The percentage rise in Medicaid spending on
      benzodiazepines since 1991 (30.0%) was less than the general rate of inflation
      (57.5%), as measured by the percentage change in the consumer price index over
      the same time period. CONCLUSIONS: Relative to the rise in the number of Medicaid
      beneficiaries (more than doubled over the study period), there is no evidence of
      an extraordinary rise in the utilization of benzodiazepines. Moreover, both
      nominal and real average prices of benzodiazepines have fallen, primarily because
      of generic entry over the last 2 decades.

PMID- 22454449
TI  - Perspective on personal and professional development.

PMID- 22454451
TI  - Collagen-binding proteins in age-dependent changes in renal collagen turnover:
      microarray analysis of mRNA expression.
AB  - Aging is associated with progressive structural and functional deterioration of
      the kidney. Among the morphological changes associated with renal aging is an
      accumulation of extracellular matrix (ECM) in the glomeruli and
      tubuloinsterstitium, which may ultimately lead to the development of renal
      fibrosis. The mechanisms governing the regulation of ECM metabolism during renal
      aging are only incompletely defined. We present data from a genome-wide mRNA
      expression study on renal tissue from 90 wk old male Wistar rats and 10 wk old
      controls using Illumina BeadArray cDNA microarray. Regulation of candidate gene
      products was verified by real-time PCR. Morphological changes were evaluated by
      routine histological methods. Activated fibroblasts were identified by their
      expression of alpha-smooth muscle actin and collagen I. Morphological analysis
      demonstrated an expansion of the tubulointerstitial compartment with increased
      amounts of fibrous collagen but no overt glomerular or tubular damage in the aged
      rats. Activated fibroblasts were readily detectable in the adventitial layer of
      large renal vessels in controls and were not found in the old animals. In
      agreement with this finding, gene expression analysis revealed significant
      downregulation of collagen I mRNA along with numerous other ECM components.
      Concomitantly, collagen-stabilizing proteins were induced, whereas matrix
      metalloproteinase 9, an enzyme involved in collagen breakdown, was reduced. In
      conclusion, our results suggest that ECM expansion during renal aging results
      from an augmented stabilization in conjunction with a reduced breakdown of
      collagen fibers. Collagen stabilizing proteins may be essential for the control
      of renal ECM turnover and the pathogenesis of kidney fibrosis.

PMID- 22454450
TI  - Dynamic microRNA expression during the transition from right ventricular
      hypertrophy to failure.
AB  - MicroRNAs (miRs) are small, noncoding RNAs that are emerging as crucial
      regulators of cardiac remodeling in left ventricular hypertrophy (LVH) and
      failure (LVF). However, there are no data on their role in right ventricular
      hypertrophy (RVH) and failure (RVF). This is a critical question given that the
      RV is uniquely at risk in patients with congenital right-sided obstructive
      lesions and in those with systemic RVs. We have developed a murine model of RVH
      and RVF using pulmonary artery constriction (PAC). miR microarray analysis of RV
      from PAC vs. control demonstrates altered miR expression with gene targets
      associated with cardiomyocyte survival and growth during hypertrophy (miR 199a
      3p) and reactivation of the fetal gene program during heart failure (miR-208b).
      The transition from hypertrophy to heart failure is characterized by apoptosis
      and fibrosis (miRs-34, 21, 1). Most are similar to LVH/LVF. However, there are
      several key differences between RV and LV: four miRs (34a, 28, 148a, and 93) were
      upregulated in RVH/RVF that are downregulated or unchanged in LVH/LVF.
      Furthermore, there is a corresponding downregulation of their putative target
      genes involving cell survival, proliferation, metabolism, extracellular matrix
      turnover, and impaired proteosomal function. The current study demonstrates, for
      the first time, alterations in miRs during the process of RV remodeling and the
      gene regulatory pathways leading to RVH and RVF. Many of these alterations are
      similar to those in the afterload-stressed LV. miRs differentially regulated
      between the RV and LV may contribute to the RVs increased susceptibility to heart
      failure.

PMID- 22454452
TI  - Characterization of the longissimus lumborum transcriptome response to adding
      propionate to the diet of growing Angus beef steers.
AB  - Development of management paradigms that enhance the rate of gain and qualitative
      characteristics of beef carcass development has the potential to impact
      production and nutrient use efficiency but also mitigate losses to the
      environment. We used eight Black Angus beef steers (272.5 +/- 17.6 kg initial
      body wt) fed a forage-based pelleted diet alone (n = 4) or supplemented with
      sodium propionate included (n = 4) for 42 days. High-quality RNA was extracted
      from the longissimus lumborum and subjected to transcriptome sequencing using RNA
      seq technology. Trimmed reads were aligned to the bovine reference genome
      (Btau4.0, release 63) and uniquely mapped reads from control and propionate
      treatment groups were subject to further analysis using edgeR. Candidates were
      filtered to account for multiple testing and differentially expressed genes (153
      at a false discovery rate of <5%) were analyzed using Gene Ontology (GO) analysis
      (GOseq) to select terms where enrichment had occurred. Significant GO terms
      included regulation of cholesterol transport, regulation of sterol transport, and
      cellular modified amino acid metabolic process. Furthermore, the top four
      identified gene networks included lipid metabolism, small molecule biochemistry,
      carbohydrate metabolism, and molecular transport-related categories. Notably,
      changes in lipid metabolism specific genes reflect both increased oxidative and
      lipid synthetic capacities. Metabolism-related gene changes are reflective of
      expected enhancements in lean tissue accretion patterns exhibited in steers where
      high ruminal propionate relative to other short chain fatty acids is observed.
      Propionate feeding induced increased N retention in rapidly growing Angus cattle,
      and the observed alterations in LL tissue lipid metabolism-related gene networks
      are consistent with enhanced cell formation and function (protein synthesis, and
      lipogenic vs. lipolytic activities).

PMID- 22454453
TI  - Differential genomic changes caused by cholesterol- and PUFA-rich diets in
      regenerated porcine coronary endothelial cells.
AB  - Endothelial regeneration and dyslipidemia impair endothelium-dependent
      relaxation, while supplementation with fish oil (FO) prevents it. The genomic
      impact of different diets was compared in primary cultures derived from native
      and regenerated endothelial cells. Pigs were fed with high-cholesterol (CHL) or
      FO-rich diet. Partial in vivo removal of endothelium was performed to induce
      endothelial regeneration. Native and regenerated cells were harvested, cultured,
      and prepared for genomic (microarray experiments, real-time PCR) and proteomic
      (Western blotting) analysis. The analysis identified genomic changes induced by
      chronic CHL diet in native cultures resembling those induced by in vivo
      regeneration, as well as those that could be prevented by FO diet. At the protein
      level, the reduced and increased presences of endothelial nitric oxide synthase
      and F2, respectively, observed after regeneration combined with CHL diet were
      alleviated by FO. The comparison of the differential changes induced by
      regeneration in vivo in endothelial cells from both diet groups revealed a
      limited number of genes as the most likely contributors to reduction in
      endothelium-dependent relaxations in porcine coronary arteries lined with
      regenerated endothelium.

PMID- 22454454
TI  - Abscisic acid deficiency antagonizes high-temperature inhibition of disease
      resistance through enhancing nuclear accumulation of resistance proteins SNC1 and
      RPS4 in Arabidopsis.
AB  - Plant defense responses to pathogens are influenced by abiotic factors, including
      temperature. Elevated temperatures often inhibit the activities of disease
      resistance proteins and the defense responses they mediate. A mutant screen with
      an Arabidopsis thaliana temperature-sensitive autoimmune mutant bonzai1 revealed
      that the abscisic acid (ABA)-deficient mutant aba2 enhances resistance mediated
      by the resistance (R) gene suppressor of npr1-1 constitutive1 (SNC1) at high
      temperature. ABA deficiency promoted nuclear accumulation of SNC1, which was
      essential for it to function at low and high temperatures. Furthermore, the
      effect of ABA deficiency on SNC1 protein accumulation is independent of salicylic
      acid, whose effects are often antagonized by ABA. ABA deficiency also promotes
      the activity and nuclear localization of R protein resistance to Pseudomonas
      syringae4 at higher temperature, suggesting that the effect of ABA on R protein
      localization and nuclear activity is rather broad. By contrast, mutations that
      confer ABA insensitivity did not promote defense responses at high temperature,
      suggesting either tissue specificity of ABA signaling or a role of ABA in defense
      regulation independent of the core ABA signaling machinery. Taken together, this
      study reveals a new intersection between ABA and disease resistance through R
      protein localization and provides further evidence of antagonism between abiotic
      and biotic responses.

PMID- 22454456
TI  - Monitoring in the management of atrial fibrillation.
AB  - We performed a survey on current practice of atrial fibrillation (AF) detection
      and monitoring and its relevance in patient management among the European Heart
      Rhythm Association Research Network. The focus of this questionnaire is on the
      use and relevance of remote AF detection in device patients and its clinical
      consequences like starting oral anticoagulation or improving device programming
      to avoid inappropriate shock therapy. Remote device data are already used by
      76.8% of the centres in their implantable cardioverter defibrillator/cardiac
      resynchronization therapy device patients to detect AF and trigger relevant
      clinical decision making! The majority of these centres are also asking for the
      option of remote device programming.

PMID- 22454455
TI  - A maize cystatin suppresses host immunity by inhibiting apoplastic cysteine
      proteases.
AB  - Ustilago maydis is a biotrophic pathogen causing maize (Zea mays) smut disease.
      Transcriptome profiling of infected maize plants indicated that a gene encoding a
      putative cystatin (CC9) is induced upon penetration by U. maydis wild type. By
      contrast, cc9 is not induced after infection with the U. maydis effector mutant
      Deltapep1, which elicits massive plant defenses. Silencing of cc9 resulted in a
      strongly induced maize defense gene expression and a hypersensitive response to
      U. maydis wild-type infection. Consequently, fungal colonization was strongly
      reduced in cc9-silenced plants, while recombinant CC9 prevented salicylic acid
      (SA)-induced defenses. Protease activity profiling revealed a strong induction of
      maize Cys proteases in SA-treated leaves, which could be inhibited by addition of
      CC9. Transgenic maize plants overexpressing cc9-mCherry showed an apoplastic
      localization of CC9. The transgenic plants showed a block in Cys protease
      activity and SA-dependent gene expression. Moreover, activated apoplastic Cys
      proteases induced SA-associated defense gene expression in naive plants, which
      could be suppressed by CC9. We show that apoplastic Cys proteases play a pivotal
      role in maize defense signaling. Moreover, we identified cystatin CC9 as a novel
      compatibility factor that suppresses Cys protease activity to allow biotrophic
      interaction of maize with the fungal pathogen U. maydis.

PMID- 22454457
TI  - High pregnancy rate after microsurgical tubal reanastomosis by temporary loose
      parallel 4-quadrant sutures technique: a long long-term follow-up report on 961
      cases.
AB  - BACKGROUND: Only a limited portion of sterilized women undergo tubal
      reanastomosis due to high costs, limited availability of qualified practitioners
      willing to perform the procedure and increasing success rates with IVF. However,
      IVF has complications and an increased risk of ectopic pregnancy and multiple
      pregnancies. Recently, the importance of specialized training for tubal
      anastomosis has been re-emphasized. This study aimed to report the procedure of
      our microsurgical tubal reanastomosis by a temporary loose parallel 4-quadrant
      suture technique and its high pregnancy outcome over the last 20 years. METHODS:
      This clinical study retrospectively analyzed data on 961 consecutive patients who
      underwent tubal reversal between March 1988 and August 2007 in a large urban
      medical center. All surgical operations were performed by microsurgical tubal
      reanastomosis using a temporary loose parallel 4-quadrant suture technique by a
      single surgeon. Subsequent pregnancy outcomes were evaluated. RESULTS: The
      overall pregnancy rate was 85.1, 82.6 being intrauterine and 2.5% ectopic. The
      pregnancy rate was significantly reduced in patients over 40 years old (53.9%)
      compared with patients aged 40 years or less (90.3%) (P < 0.05). Repair done at
      the interstitial-ampulla site yielded a significantly higher ectopic pregnancy
      rate (20.0%) compared with other anastomosis sites (0-3.2%) (P < 0.001).
      CONCLUSIONS: This study shows that our technique resulted in a high pregnancy
      rate comparable with the level of natural fertility. The study also reveals that
      ectopic pregnancy frequently occurs in tubal reanastomosis of the interstitial
      ampulla site compared with other sites.

PMID- 22454458
TI  - Efficiency and purity provided by the existing methods for the isolation of
      luteinized granulosa cells: a comparative study.
AB  - BACKGROUND: Several protocols for the isolation of luteinized granulosa cells
      (LGCs) contained in follicular fluid have been described but no previously
      published study has compared the relative efficiency of these protocols. Our
      objective is to obtain conclusive scientific evidence for the superiority of one
      method over another. METHODS: Different purification methods for LGCs based on
      the recognition of specific cell markers, aggregates, differential adhesion and
      LGC size were evaluated. We compared the levels of CD45 cell contamination and
      the percentage of total cell viability in paired aliquots of cells (before and
      after purification) derived from the follicular fluid obtained from women who
      were donating oocytes (n = 72). Each of the six purification methods was
      performed six times using pooled follicular fluids from two women. RESULTS:
      Samples processed by means of recognition of specific cell markers were
      characterized by their greater purity (0.1-1.33% CD45+) but low rate of LGC
      recovery (17.13-25.4%) when compared with the other methods (3.29-12% CD45+, P <
      0.05 and 51.67-73.20% LGC, P < 0.05). It is noteworthy that the filter method,
      which is based on the LGC size, combined one of the highest rates of LGC recovery
      (~70%) with acceptable low levels of contamination (<5%). CONCLUSIONS: There is
      currently no gold standard method for the isolation of LGCs, and protocols should
      be chosen depending on the purpose in question. We conclude that fluorescence
      activated cell sorting is the best protocol for isolating LGCs when purity is the
      principal criterion, and magnetic separation when both purity and viability are
      essential. However, cell straining (filter) is probably the least laborious and,
      overall, the most efficient method to isolate LGCs.

PMID- 22454459
TI  - Uterus transplantation in a non-human primate: long-term follow-up after
      autologous transplantation.
AB  - BACKGROUND: Uterus transplantation (UTx) may provide the first available
      treatment for women affected by uterine infertility. The present study aimed to
      further develop a surgical technique for autologous UTx in a non-human primate
      species and to assess long-term function. METHODS: Female baboons (n= 16)
      underwent autologous transplantation of the uterus with the Fallopian tubes and
      ovaries, performed with a previously published surgical technique (n= 6, Group 1)
      or using a modified technique (n= 10; Group 2). The uterine arteries were
      dissected to the proximal end of the anterior branch (Group 1) or the entire
      (Group 2) internal iliac artery, and the ovarian veins were dissected to the
      crossing over the ureter (Group 1) or further cranially to include greater
      lengths and patches of the cava/renal vein (Group 2). Back-table preparation
      created common venous and arterial ends with arterial anastomosis either end-to
      side to the left external iliac artery (Group 1) or end-to-end to the left
      internal iliac artery (Group 2). RESULTS: Overall short-time survival of the
      animals was 88% (66% in Group 1 and 100% in Group 2). Of all the operated
      animals, 75% (66% in Group 1 and 80% in Group 2) resumed ovarian cyclicity.
      Regular menstruation after UTx was demonstrated only in Group 2 (60%).
      Menstruating animals (n= 6) were each exposed to timed mating for >=5 menstrual
      cycles, but pregnancy did not occur. Adhesions and tubal blockage were seen in
      post-mortem analysis. CONCLUSIONS: The modified UTx model of Group 2 is a safe
      procedure and shows resumed long-term uterine function in a majority of the
      animals, although pregnancy could not be demonstrated.

PMID- 22454460
TI  - Validation of a new metabolic marker to assess the vascular viability of
      vitrified whole sheep ovaries.
AB  - BACKGROUND: Whole ovary cryopreservation has been suggested as a means to
      preserve fertility. In animal models, autologous cryopreserved ovary transplants
      frequently undergo thrombosis and a method to assess the vascular viability of
      cryopreserved ovaries would be valuable. We developed a staining method using
      methylthiazolyl blue tetrazolium (MTT, a metabolic marker) to assess the pedicle
      metabolism of whole ovaries vitrified using cryoprotectant called 'VS4'. METHODS:
      Whole sheep ovaries were perfused with MTT (1 g/l). In one group, ovarian tissue
      lesions were induced by immersing the ovarian pedicle in medium at 53 degrees C
      or 65 degrees C or in liquid nitrogen prior to MTT perfusion. In the second
      group, several metabolic substrates (d-glucose, l-glucose and pyruvic acid) and
      inhibitors [2-deoxy-d-glucose for d-glucose metabolism, azide for mitochondrial
      respiration and diphenyleneiodonium (DPI) for NADPH oxidase (an effector of the
      pentose phosphate pathway)] were added to the MTT stain. The third group was
      subjected to VS4 +/- vitrification/warming prior to MTT perfusion. Pedicle MTT
      staining was assessed qualitatively by histological examination of frozen
      sections or quantified at 564 nm after solubilization in alcohol. RESULTS: MTT
      strongly and reproducibly stained the vascular smooth muscle. Heating at 53
      degrees C or 65 degrees C or cooling in liquid nitrogen significantly diminished
      MTT staining by 48% (P = 0.001, n = 10), 94% (P = 0.0002, n = 10) and 94% (P =
      0.0002, n = 10), respectively. MTT staining was affected by d-glucose metabolism:
      absence of d-glucose, substitution of unmetabolized l-glucose for d-glucose or
      addition of 2-deoxy-d-glucose significantly decreased MTT staining by 44% (P <
      0.01, n = 10), 45% (P < 0.01, n = 10) and 29% (P < 0.01, n = 10), respectively.
      Pyruvic acid failed to correct the MTT staining decrease induced by d-glucose
      deprivation and azide did not decrease MTT staining, suggesting that MTT staining
      could be independent of mitochondrial metabolism. Adding DPI significantly
      inhibited MTT staining by 25% (P < 0.001, n = 10), suggesting involvement of the
      pentose phosphate pathway's effectors. Compared with controls, VS4
      vitrified/warmed pedicles showed significantly less MTT staining (-30%, P <
      0.005, n = 10), with unstained foci, whereas unvitrified VS4-exposed pedicles
      showed no difference. CONCLUSIONS: MTT can serve as a qualitative and
      quantitative vascular viability marker.VS4 vitrification caused alterations in
      ovarian vascular metabolism. MTT staining should allow accurate comparisons of
      whole-organ cryoprotection protocols.

PMID- 22454461
TI  - Impact of intraperitoneal pressure of a CO2 pneumoperitoneum on the surgical
      peritoneal environment.
AB  - BACKGROUND: Animal experiments have suggested that a high intraperitoneal
      pressure (IPP) might adversely affect the surgical peritoneal environment. The
      present experimental study investigates the impact of IPP of a CO(2)
      pneumoperitoneum on human peritoneum. METHODS: Patients undergoing laparoscopic
      surgery were subjected to either low (8 mmHg) or standard (12 mmHg) IPP. Normal
      peritoneum was collected from the parietal wall at the beginning of surgery and
      every 60 min thereafter. Expression levels of 168 genes that encode extracellular
      matrix proteins, adhesion molecules or inflammatory cytokine signaling molecules
      were measured in peritoneal tissues using real-time polymerase chain reaction
      (PCR)-based assay panels. Human peritoneal mesothelial cells (HPMCs) and human
      peritoneal fibroblasts (HPFBs) were incubated in a CO(2) insufflation chamber for
      1 h at 12 or 8 mmHg. Hyaluronan (HA) synthesis and mRNA expression levels of
      hyaluronic acid synthases (HAS) and hyaluronidases (Hyal) in HPMCs and HPFBs were
      measured at 0, 4, 8, 12, 24 and 48 h after CO(2) gas exposure by ELISA and real
      time PCR, respectively. RESULTS: Expression levels of connective tissue growth
      factor (CTGF), matrix metalloproteinase-9, E-selectin, chemokine (C-X-C motif)
      ligand 2 (CXCL-2), Hyal-1 and Hyal-2 were significantly higher and those of HAS
      1, HAS-3, thrombospondin-2 (TSP-2) and interleukin-10 were significantly lower in
      the 12 mmHg group compared with the 8 mmHg group. HA synthesis was significantly
      lower in the 12 mmHg group compared with the 8 mmHg group in HPMCs and HPFBs
      throughout the time course. CONCLUSIONS: A low IPP (8 mmHg) may be better than
      the standard IPP (12 mmHg) to minimize the adverse impact on the surgical
      peritoneal environment during a CO(2) pneumoperitoneum.

PMID- 22454462
TI  - Host gene expression changes correlating with anti-HIV-1 effects in human
      subjects after treatment with peginterferon Alfa-2a.
AB  - We investigated whether interferon-inducible genes (IFIGs) with known anti-human
      immunodeficiency virus (HIV) activity in vitro were associated with in vivo
      virological response in HIV infection. Nine untreated HIV-1-infected volunteers
      were treated for 12 weeks with peginterferon alfa-2a. A subset of IFIGs (23 of
      47) increased compared with baseline through 6 weeks beyond therapy, and 10 of
      the 23 IFIGs significantly inversely correlated (r = -0.7; P < .05) with
      virological response. The strength of peginterferon alfa-2a-induced IFIG response
      significantly correlated with declines in HIV load during treatment (r(2) = 0.87,
      p = .003). This study links HIV virological response to a specific IFIG subset, a
      potential prognostic indicator in peginterferon alfa-2a-treated patients with HIV
      infection.

PMID- 22454463
TI  - Decreased interleukin 7 responsiveness of T lymphocytes in patients with
      idiopathic CD4 lymphopenia.
AB  - BACKGROUND: Elevated serum interleukin 7 (IL-7) levels are observed in
      lymphopenic conditions, including idiopathic CD4 lymphopenia (ICL), which is
      characterized by CD4 lymphopenia in the absence of human immunodeficiency virus
      infection or other known immunodeficiency. METHODS: To test whether defective IL
      7 signaling could be an etiologic or contributing factor in ICL, peripheral blood
      mononuclear cells from patients with ICL (median CD4 T-cell count, 160 cells/MUL)
      and healthy controls (median CD4 T-cell count, 582 cells/MUL) were evaluated for
      expression of IL-7Ralpha chain (CD127) and intracellular phosphorylated STAT-5 (a
      marker of gammac cytokine signaling) after cytokine stimulation. Gene expression
      was analyzed by real-time polymerase chain reaction following IL-7 stimulation.
      RESULTS: The percentage of CD4+CD127+ T cells was lower in patients with ICL,
      compared with controls (P < .001). Lower levels of STAT-5 phosphorylation after
      IL-7 stimulation were observed in both CD4 and CD8 T cells from patients with
      ICL, compared with controls (P < .001 and P = .017, respectively), that inversely
      correlated in CD4 T cells with serum IL-7 levels (r = -0.734, P = .013).
      Destabilization of p27(kip1), a critical step for IL-7-induced T-cell cycling,
      was decreased in patients with ICL, compared with controls (P = .004), after IL-7
      stimulation. CONCLUSIONS: These data suggest that diminished responsiveness to IL
      7 in CD4 and CD8 T cells during ICL may be contributing to the dysregulation of T
      cell homeostasis.

PMID- 22454464
TI  - Novel in vitro and in vivo models and potential new therapeutics to break the
      vicious cycle of Cryptosporidium infection and malnutrition.
AB  - BACKGROUND: Although several animal models of cryptosporidiosis have been
      reported, most involve genetically or pharmacologically immune-suppressed hosts.
      METHODS: We report challenge with excysted (in vitro and in vivo) and unexcysted
      (in vivo) Cryptosporidium parvum oocysts in human colonic adenocarcinoma (HCT-8)
      cells and weaned nourished and malnourished C57BL/6 mice, following outcomes of
      growth rate, stool shedding, and tissue burden. We tested treatment with an
      oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) and alanyl
      glutamine in vivo and in vitro. RESULTS: C. parvum-challenged mice showed
      prolonged weight loss (>10% over 4 days), robust stool shedding (>3 logs/d over 7
      days), and epithelial infection in the ileum, cecum, and colon. Of 2 potential
      therapeutic compounds evaluated in the model, CpG-ODN reduced body weight loss
      (to <6% on days 3-7 after challenge), reduced shedding of organisms (by 25% on
      days 1 and 3 after challenge), and decreased the burden of parasites in the
      ileum. Alanyl-glutamine showed similar benefits. In vitro findings suggested that
      effects on the epithelial component of the mucosa probably likely responsible for
      beneficial effects seen in vivo. CONCLUSIONS: Weaned mice provide a convenient
      and reproducible model of cryptosporidial disease, including its vicious cycle
      with body weight loss and heavier infection with malnutrition, and this model may
      be useful in exploring innovative therapeutic solutions for this challenging
      infectious disease.

PMID- 22454465
TI  - Impact of persistent HIV replication on CD4 negative Vgamma2Vdelta2 T cells.
AB  - BACKGROUND: CD4- Vgamma2Vdelta2 T cells are depleted during human
      immunodeficiency virus (HIV) infection but can recover to near normal levels in
      patients who spontaneously control viremia in the absence of therapy. By
      contrasting Vgamma2Vdelta2 T-cell numbers, phenotype, and T-cell receptor (TCR)
      repertoire, we investigate the dynamic tension between active immunity and
      progressive T-cell destruction during persistent viremia. METHODS: Peripheral
      blood Vgamma2Vdelta2 T-cell levels and phenotypes were characterized by flow
      cytometry. Lymphoproliferation assays measured functional responses.
      Spectratyping characterized damage to the TCR repertoire. RESULTS: Levels,
      responses to antigen and the proportion of T effector memory Vgamma2Vdelta2 T
      cells in patients with persistent viremia, were intermediate between patients
      with natural virus suppression (NVS) and patients receiving antiretroviral
      therapy. Damage to the TCR gamma-2 chain repertoire and depletion of CD56+
      Vgamma2Vdelta2 T cells were more pronounced in viremic patients, compared with
      antiretroviral therapy recipients and patients with natural virus suppression.
      CONCLUSIONS: Characteristics of Vgamma2Vdelta2 T cells in viremic patients
      reflect both active responses (increasing cell numbers, better antigen responses,
      and higher proportion of effector memory cells) and ongoing damage (repertoire
      changes and loss of CD56+ cells). Unlike patients who control viremia to
      undetectable levels, Vgamma2Vdelta2 T cells are diminished during persistent
      viremia and may eventually be lost because of progressive destruction of the TCR
      repertoire.

PMID- 22454466
TI  - Dynamics of Plasmodium falciparum selection after artemether-lumefantrine
      treatment in Africa.

PMID- 22454467
TI  - Transmission of varicella zoster virus from individuals with herpes zoster or
      varicella in school and day care settings.
AB  - BACKGROUND: Because the varicella incidence has declined following varicella
      vaccine licensure, herpes zoster (HZ) cases may play a larger role in varicella
      zoster virus (VZV) transmission. We investigated how HZ and varicella cases
      contribute to the varicella incidence in schools and day care centers. METHODS:
      Surveillance data collected in Philadelphia during September 2003-June 2010 were
      analyzed. A varicella case was considered to be sporadic if it was reported from
      a school or day care facility >6 weeks after or >=10 days before other reports of
      VZV transmission. A varicella case was considered to be secondary if it occurred
      10-21 days after report of a case of HZ or sporadic varicella. Analysis compared
      VZV transmission from individuals with HZ or sporadic varicella, stratified by
      varicella vaccination status and disease severity. RESULTS: Of 290 HZ cases
      reported, 27 (9%) resulted in 84 secondary varicella cases. Of 1358 sporadic
      varicella cases reported, 205 (15%) resulted in 564 secondary varicella cases.
      Approximately half of the HZ and sporadic varicella cases resulted in single
      secondary cases. The proportion of individuals who had secondary cases with mild
      disease was similar for those exposed to HZ and those exposed to varicella (70%
      and 72%, respectively). VZV transmission was highest from unvaccinated
      individuals with sporadic varicella (P < .01). CONCLUSIONS: VZV transmission from
      individuals with HZ contributes to varicella morbidity. More research is needed
      to understand risk factors and guide recommendations for preventing VZV
      transmission from individuals with HZ.

PMID- 22454468
TI  - The etiology of severe acute gastroenteritis among adults visiting emergency
      departments in the United States.
AB  - BACKGROUND: Acute gastroenteritis (AGE) remains a common cause of clinic visits
      and hospitalizations in the United States, but the etiology is rarely determined.
      METHODS: We performed a prospective, multicenter emergency department-based study
      of adults with AGE. Subjects were interviewed on presentation and 3-4 weeks
      later. Serum samples, rectal swab specimens, and/or whole stool specimens were
      collected at presentation, and serum was collected 3-4 weeks later. Fecal
      specimens were tested for a comprehensive panel of viral, bacterial, and
      parasitic pathogens; serum was tested for calicivirus antibodies. RESULTS:
      Pathogens were detected in 25% of 364 subjects, including 49% who provided a
      whole stool specimen. The most commonly detected pathogens were norovirus (26%),
      rotavirus (18%), and Salmonella species (5.3%). Pathogens were detected
      significantly more often from whole stool samples versus a rectal swab specimen
      alone. Nine percent of subjects who provided whole stool samples had >1 pathogen
      identified. CONCLUSIONS: Viruses, especially noroviruses, play a major role as
      agents of severe diarrhea in adults. Further studies to confirm the unexpectedly
      high prevalence of rotaviruses and to explore the causes of illness among
      patients from whom a pathogen cannot be determined are needed. Studies of enteric
      pathogens should require the collection of whole stool samples.

PMID- 22454470
TI  - How useful are stool studies for acute gastroenteritis?

PMID- 22454471
TI  - Varicella zoster virus transmission in the vaccine era: unmasking the role of
      herpes zoster.

PMID- 22454472
TI  - Creating a mammalian-transmissible A/H5N1 influenza virus: social contracts,
      prudence, and alternative perspectives.

PMID- 22454473
TI  - Biosecurity and censorship: the H5N1 influenza controversy.

PMID- 22454474
TI  - The future of research and publication on altered H5N1 viruses.
AB  - Recently, we and others obtained experimental evidence that highly pathogenic
      avian influenza virus subtype H5 can acquire the ability to transmit via aerosols
      between ferrets. Upon submission of manuscripts describing the results of these
      studies, the US National Science Advisory Board for Biosecurity was consulted and
      recommended that the main conclusions of the work be published but without the
      experimental details and mutation data that would enable replication of the
      experiments. Over the past few months, these events have led to intense
      discussions. Should this type of experiment be conducted? If so, under what
      conditions? Do the scientific and public health benefits of the work and its
      publication outweigh the potential risks? In February 2012, public health and
      influenza experts discussed these issues during a World Health Organization
      organized technical consultation. This perspective article reviews the current
      state of the field and the recommendations made during the meeting.

PMID- 22454475
TI  - The science of security versus the security of science.

PMID- 22454476
TI  - LXRalpha is uniquely required for maximal reverse cholesterol transport and
      atheroprotection in ApoE-deficient mice.
AB  - The liver X receptor (LXR) signaling pathway is an important modulator of
      atherosclerosis, but the relative importance of the two LXRs in atheroprotection
      is incompletely understood. We show here that LXRalpha, the dominant LXR isotype
      expressed in liver, plays a particularly important role in whole-body sterol
      homeostasis. In the context of the ApoE(-/-) background, deletion of LXRalpha,
      but not LXRbeta, led to prominent increases in atherosclerosis and peripheral
      cholesterol accumulation. However, combined loss of LXRalpha and LXRbeta on the
      ApoE(-/-) background led to an even more severe cholesterol accumulation
      phenotype compared to LXRalpha(-/-)ApoE(-/-) mice, indicating that LXRbeta does
      contribute to reverse cholesterol transport (RCT) but that this contribution is
      quantitatively less important than that of LXRalpha. Unexpectedly, macrophages
      did not appear to underlie the differential phenotype of LXRalpha(-/-)ApoE(-/-)
      and LXRbeta(-/-)ApoE(-/-) mice, as in vitro assays revealed no difference in the
      efficiency of cholesterol efflux from isolated macrophages. By contrast, in vivo
      assays of RCT using exogenously labeled macrophages revealed a marked defect in
      fecal sterol efflux in LXRalpha(-/-)ApoE(-/-) mice. Mechanistically, this defect
      was linked to a specific requirement for LXRalpha(-/-) in the expression of
      hepatic LXR target genes involved in sterol transport and metabolism. These
      studies reveal a previously unrecognized requirement for hepatic LXRalpha for
      optimal reverse cholesterol transport in mice.

PMID- 22454478
TI  - Is the J-shaped curve related to vascular mortality?

PMID- 22454477
TI  - Sphingosine mediates TNFalpha-induced lysosomal membrane permeabilization and
      ensuing programmed cell death in hepatoma cells.
AB  - Normally, cell proliferation and death are carefully balanced in higher
      eukaryotes, but one of the most important regulatory mechanisms, apoptosis, is
      upset in many malignancies, including hepatocellular-derived ones. Therefore,
      reinforcing cell death often is mandatory in anticancer therapy. We previously
      reported that a combination of tumor necrosis factor-alpha (TNF) and
      cycloheximide (CHX) efficiently kill HTC cells, a rat hepatoma line, in an
      apoptosis-like mode. Death is actively mediated by the lysosomal compartment,
      although lysosomal ceramide was previously shown not to be directly implicated in
      this process. In the present study, we show that TNF/CHX increase lysosomal
      ceramide that is subsequently converted into sphingosine. Although ceramide
      accumulation does not significantly alter the acidic compartment, the sphingosine
      therein generated causes lysosomal membrane permeabilization (LMP) followed by
      relocation of lysosomal cathepsins to the cytoplasm. TNF/CHX-induced LMP is
      effectively abrogated by siRNAs targeting acid sphingomyelinase or acid
      ceramidase, which prevent both LMP and death induced by TNF/CHX. Taken together,
      our results demonstrate that lysosomal accumulation of ceramide is not
      detrimental per se, whereas its degradation product sphingosine, which has the
      capacity to induce LMP, appears responsible for the observed apoptotic-like
      death.

PMID- 22454479
TI  - Endothelial caveolar hub regulation of adenosine triphosphate-induced endothelial
      nitric oxide synthase subcellular partitioning and domain-specific
      phosphorylation.
AB  - ATP leads to endothelial NO synthase (eNOS)/NO-mediated vasodilation, a process
      hypothesized to depend on the endothelial caveolar eNOS partitioning and
      subcellular domain-specific multisite phosphorylation state. We demonstrate
      herein that, in both the absence and presence of ATP, the uterine artery
      endothelial caveolae contain specific protein machinery related to subcellular
      partitioning and act as specific focal "hubs" for NO- and ATP-related proteins.
      ATP-induced eNOS regulation showed a complex set of multisite posttranslational
      phosphorylation events that were closely associated with the enzyme's
      partitioning between caveolar and noncaveolar endothelial subcellular domains.
      The comprehensive model that we present demonstrates that ATP repartitioned eNOS
      between the caveolar and noncaveolar subcellular domains; specifically, the
      stimulatory (PSer635)eNOS was substantially higher in the caveolar pool with
      subcellular domain-independent increased levels on ATP treatment. The stimulatory
      (PSer1179)eNOS was not altered by ATP treatment. However, the inhibitory
      (PThr495)eNOS was regulated predominantly in the caveolar domain with decreased
      levels on ATP action. In contrast, the agonist-specific (PSer114)eNOS was
      localized in the noncaveolar pool with increased levels on ATP stimulation. Thus,
      the endothelial caveolar membrane system plays a pivotal role(s) in ATP
      associated subcellular partitioning and possesses the relevant protein machinery
      for ATP-induced NO regulation. Furthermore, these subcellular domain-specific
      phosphorylation/dephosphorylation events provide evidence relating to eNOS spatio
      temporal dynamics.

PMID- 22454480
TI  - Peroxisome proliferator-activated receptor-gamma activation with angiotensin II
      type 1 receptor blockade is pivotal for the prevention of blood-brain barrier
      impairment and cognitive decline in type 2 diabetic mice.
AB  - We reported previously that an angiotensin II type 1 receptor blocker,
      telmisartan, improved cognitive decline with peroxisome proliferator-activated
      receptor-gamma activation; however, the detailed mechanisms are unclear. Enhanced
      blood-brain barrier (BBB) permeability with alteration of tight junctions is
      suggested to be related to diabetes mellitus. Therefore, we examined the
      possibility that telmisartan could attenuate BBB impairment with peroxisome
      proliferator-activated receptor-gamma activation to improve diabetes mellitus
      induced cognitive decline. Type 2 diabetic mice KKA(y) exhibited impairment of
      cognitive function, and telmisartan treatment attenuated this. Cotreatment with
      GW9662, a peroxisome proliferator-activated receptor-gamma antagonist, interfered
      with these protective effects of telmisartan against cognitive function. BBB
      permeability was increased in both the cortex and hippocampus in KKA(y) mice.
      Administration of telmisartan attenuated this increased BBB permeability.
      Coadministration of GW9662 reduced this effect of telmisartan. Significant
      decreases in expression of tight junction proteins and increases in matrix
      metalloproteinase expression, oxidative stress, and proinflammatory cytokine
      production were observed in the brain, and treatment with telmisartan restored
      these changes. Swollen astroglial end-feet in BBB were observed in KKA(y) mice,
      and this change in BBB ultrastructure was decreased in telmisartan. These effects
      of telmisartan were weakened by cotreatment with GW9662. In contrast,
      administration of another angiotensin II type 1 receptor blocker, losartan, was
      less effective compared with telmisartan in terms of preventing BBB permeability
      and astroglial end-foot swelling, and coadministration of GW9662 did not affect
      the effects of losartan. These findings are consistent with the possibility that,
      in type 2 diabetic mice, angiotensin II type 1 receptor blockade with peroxisome
      proliferator-activated receptor-gamma activation by telmisartan may help with
      protection against cognitive decline by preserving the integrity of the BBB.

PMID- 22454481
TI  - Poly(ADP-ribose) polymerase 1 inhibition improves coronary arteriole function in
      type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is associated with microvascular dysfunction. We
      hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity
      contributes to microvascular dysfunction in T2DM. T2DM (db(-)/db(-)) and
      nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1
      inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
      Isolated coronary arterioles were mounted in an arteriograph. Pressure-induced
      myogenic tone was significantly potentiated, whereas endothelium-dependent
      relaxation was significantly attenuated in diabetic mice compared with control
      mice. These results were associated with decreased endothelial NO synthase
      phosphorylation and cGMP level and increased PARP-1 activity in coronary
      arterioles from diabetic mice compared with control mice. Interestingly, PARP-1
      inhibitors significantly reduced the potentiation of myogenic tone, improved
      endothelium-dependent relaxation, restored endothelial NO synthase
      phosphorylation and cGMP, and attenuated cleaved PARP-1. These results were
      supported by in vitro studies indicating that downregulation of PARP-1 in
      mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral
      particles significantly improved endothelium-dependent relaxation in mesenteric
      resistance arteries from diabetic mice compared with control mice. The inhibition
      of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly
      reduced the endothelium-dependent relaxation in coronary arterioles and
      mesenteric resistance arteries from control and diabetic mice treated with PARP-1
      inhibitors and PARP-1 short hairpin RNA lentiviral particles. In addition, we
      demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage
      were reduced after PARP-1 inhibition in cultured endothelial cells stimulated
      with high glucose. We provide evidence that T2DM impairs microvascular function
      by an enhanced PARP-1 activity-dependent mechanism. Therefore, PARP-1 could be a
      potential target for overcoming diabetic microvascular complications.

PMID- 22454482
TI  - SNM practice guideline for parathyroid scintigraphy 4.0.

PMID- 22454483
TI  - Segmentectomy for giant pulmonary sclerosing haemangiomas with high serum KL-6
      levels.
AB  - We describe a 61-year old female patient with a giant pulmonary sclerosing
      haemangioma (PSH) and an extremely high preoperative serum KL-6 level. During an
      annual health screening, the patient showed a posterior mediastinal mass on chest
      radiography. Chest computed tomography and magnetic resonance imaging revealed a
      well-circumscribed 60 mm diameter nodule with a marked contrast enhancement in
      the left lower lobe. The preoperative serum KL-6 level was elevated to 8204 U/ml.
      We performed a four-port thoracoscopic basal segmentectomy and lymph node
      sampling for diagnosis and therapy. The postoperative diagnosis showed PSH. The
      serum KL-6 level decreased dramatically with tumour resection. To the best of our
      knowledge, this is the first report of a patient with PSH showing a high serum KL
      6 level.

PMID- 22454484
TI  - Reproducibility of tumor uptake heterogeneity characterization through textural
      feature analysis in 18F-FDG PET.
AB  - (18)F-FDG PET measurement of standardized uptake value (SUV) is increasingly used
      for monitoring therapy response and predicting outcome. Alternative parameters
      computed through textural analysis were recently proposed to quantify the
      heterogeneity of tracer uptake by tumors as a significant predictor of response.
      The primary objective of this study was to evaluate the reproducibility of these
      heterogeneity measurements. METHODS: Double baseline (18)F-FDG PET scans were
      acquired within 4 d of each other for 16 patients before any treatment was
      considered. A Bland-Altman analysis was performed on 8 parameters based on
      histogram measurements and 17 parameters based on textural heterogeneity features
      after discretization with values between 8 and 128. RESULTS: The reproducibility
      of maximum and mean SUV was similar to that in previously reported studies, with
      a mean percentage difference of 4.7% +/- 19.5% and 5.5% +/- 21.2%, respectively.
      By comparison, better reproducibility was measured for some textural features
      describing local heterogeneity of tracer uptake, such as entropy and homogeneity,
      with a mean percentage difference of -2% +/- 5.4% and 1.8% +/- 11.5%,
      respectively. Several regional heterogeneity parameters such as variability in
      the intensity and size of regions of homogeneous activity distribution had
      reproducibility similar to that of SUV measurements, with 95% confidence
      intervals of -22.5% to 3.1% and -1.1% to 23.5%, respectively. These parameters
      were largely insensitive to the discretization range. CONCLUSION: Several
      parameters derived from textural analysis describing heterogeneity of tracer
      uptake by tumors on local and regional scales had reproducibility similar to or
      better than that of simple SUV measurements. These reproducibility results
      suggest that these (18)F-FDG PET-derived parameters, which have already been
      shown to have predictive and prognostic value in certain cancer models, may be
      used to monitor therapy response and predict patient outcome.

PMID- 22454485
TI  - The flow-metabolic phenotype of primary colorectal cancer: assessment by
      integrated 18F-FDG PET/perfusion CT with histopathologic correlation.
AB  - The aim of this study was to assess the in vivo flow-metabolic phenotype in
      primary colorectal cancer with integrated (18)F-FDG PET/perfusion CT and its
      relationship to gold standard histopathologic assessment of angiogenesis and
      hypoxia. METHODS: 45 patients (26 male and 19 female; mean age, 67.6 y) with
      primary colorectal cancer underwent integrated (18)F-FDG PET/perfusion CT,
      deriving tumor glucose metabolism (maximum standardized uptake value) and
      regional blood flow. From this cohort, 35 underwent surgery subsequently, without
      intervening neoadjuvant treatment, allowing histopathologic correlation with
      tumor stage, CD105 microvessel density, vascular endothelial growth factor
      (VEGF), glucose transporter protein 1 (Glut-1), and hypoxia-inducible factor 1
      expression. RESULTS: The flow-metabolic ratio was significantly lower for tumors
      with higher VEGF (3.65 vs. 5.98; P = 0.01) or hypoxia-inducible factor 1
      expression (3.63 vs. 5.48; P = 0.04) versus tumors with lower expression. There
      were significant negative correlations between the tumor flow-metabolic ratio and
      VEGF expression (r = -0.55, P = 0.0008), indicating that tumors with low blood
      flow but higher metabolism were associated with higher VEGF expression. Flow and
      metabolism were coupled in higher-stage (stage III/IV) tumors but not lower-stage
      tumors (stage I/II) (r = 0.47, P = 0.03, vs. r = 0.09, P = 0.65, respectively.
      CONCLUSION: Tumors with a low-flow-high-metabolism phenotype demonstrated higher
      VEGF expression and may reflect a more angiogenic phenotype.

PMID- 22454486
TI  - [N-methyl-11C]cholylsarcosine, a novel bile acid tracer for PET/CT of hepatic
      excretory function: radiosynthesis and proof-of-concept studies in pigs.
AB  - Excretion of conjugated bile acids into bile is an essential function of the
      liver, and impairment of canalicular bile acid secretion leads to cholestatic
      liver injury. However, hepatic excretory function cannot be quantified in vivo
      because of the lack of suitable methods. Cholylsarcosine is an analog of the
      endogenous bile acid conjugate cholylglycine and exhibits characteristics in vivo
      that led us to hypothesize that the (11)C-labeled form, that is, [N-methyl
      (11)C]cholylsarcosine ((11)C-cholylsarcosine), would be a suitable PET tracer for
      quantification of hepatic excretory function. METHODS: A method for
      radiosynthesis of (11)C-cholylsarcosine was developed involving (11)C-methylation
      of glycine followed by conjugation with cholic acid. Blood-to-liver uptake and
      liver-to-bile excretion were investigated in vivo by dynamic (11)C
      cholylsarcosine PET/CT of 2 anesthetized pigs. In pig 1, a second dynamic (11)C
      cholylsarcosine PET/CT examination was preceded by a high dose of the endogenous
      bile acid conjugate cholyltaurine to investigate possible inhibition of the
      transhepatocellular transport of (11)C-cholylsarcosine. In pig 2, a second (11)C
      cholylsarcosine administration was given to determine the biodistribution of the
      tracer by means of 5 successive whole-body PET/CT recordings. Possible formation
      of (11)C-metabolites was investigated by analysis of blood and bile samples from
      a third pig. RESULTS: The radiochemical yield was 13% +/- 3% (n = 7, decay
      corrected) and up to 1.1 GBq of (11)C-cholylsarcosine was produced with a
      radiochemical purity greater than 99%. PET/CT studies showed rapid blood-to-liver
      uptake and liver-to-bile excretion of (11)C-cholylsarcosine, with radioactivity
      concentrations being more than 90 times higher in the bile ducts than in liver
      tissue. Cholyltaurine inhibited the transhepatocellular transport of (11)C
      cholylsarcosine, indicating that the tracer is transported by one or more of the
      same hepatic transporters as cholyltaurine. (11)C-cholylsarcosine underwent an
      enterohepatic circulation and reappeared in liver tissue and bile ducts after
      approximately 70 min. There were no detectable (11)C-metabolites in the plasma or
      bile samples, indicating that the novel conjugated bile acid (11)C
      cholylsarcosine was not metabolized in the liver or in the intestines. The
      effective absorbed dose of (11)C-cholylsarcosine was 4.4 MUSv/MBq. CONCLUSION: We
      have synthesized a novel conjugated bile acid analog, (11)C-cholylsarcosine, and
      PET/CT studies on anesthetized pigs showed that the hepatic handling of tracer
      uptake from blood and excretion into the bile was comparable to that for the
      endogenous bile acid cholyltaurine. This tracer may be valuable for future
      studies of normal and pathologic hepatic excretory functions in humans.

PMID- 22454488
TI  - Idiosyncratic nature of voriconazole photosensitivity in children undergoing
      cancer therapy.

PMID- 22454489
TI  - Escherichia coli producing VIM-1 carbapenemase isolated on a pig farm.

PMID- 22454490
TI  - Interleukin-6 and C-reactive protein levels after 3 years of treatment with
      darunavir/ritonavir monotherapy or darunavir/ritonavir + two nucleoside reverse
      transcriptase inhibitors in the MONET trial.

PMID- 22454491
TI  - Tigecycline-resistant Enterococcus faecalis associated with omeprazole use in a
      surgical patient.

PMID- 22454492
TI  - Edge-carboxylated graphene nanosheets via ball milling.
AB  - Low-cost, high-yield production of graphene nanosheets (GNs) is essential for
      practical applications. We have achieved high yield of edge-selectively
      carboxylated graphite (ECG) by a simple ball milling of pristine graphite in the
      presence of dry ice. The resultant ECG is highly dispersable in various solvents
      to self-exfoliate into single- and few-layer (<= 5 layers) GNs. These stable ECG
      (or GN) dispersions have been used for solution processing, coupled with thermal
      decarboxylation, to produce large-area GN films for many potential applications
      ranging from electronic materials to chemical catalysts. The electrical
      conductivity of a thermally decarboxylated ECG film was found to be as high as
      1214 S/cm, which is superior to its GO counterparts. Ball milling can thus
      provide simple, but efficient and versatile, and eco-friendly (CO(2)-capturing)
      approaches to low-cost mass production of high-quality GNs for applications where
      GOs have been exploited and beyond.

PMID- 22454493
TI  - Folding without charges.
AB  - Surface charges of proteins have in several cases been found to function as
      "structural gatekeepers," which avoid unwanted interactions by negative design,
      for example, in the control of protein aggregation and binding. The question is
      then if side-chain charges, due to their desolvation penalties, play a
      corresponding role in protein folding by avoiding competing, misfolded traps? To
      find out, we removed all 32 side-chain charges from the 101-residue protein S6
      from Thermus thermophilus. The results show that the charge-depleted S6 variant
      not only retains its native structure and cooperative folding transition, but
      folds also faster than the wild-type protein. In addition, charge removal
      unleashes pronounced aggregation on longer timescales. S6 provides thus an
      example where the bias toward native contacts of a naturally evolved protein
      sequence is independent of charges, and point at a fundamental difference in the
      codes for folding and intermolecular interaction: specificity in folding is
      governed primarily by hydrophobic packing and hydrogen bonding, whereas
      solubility and binding relies critically on the interplay of side-chain charges.

PMID- 22454495
TI  - Impact of the Deepwater Horizon oil spill on a deep-water coral community in the
      Gulf of Mexico.
AB  - To assess the potential impact of the Deepwater Horizon oil spill on offshore
      ecosystems, 11 sites hosting deep-water coral communities were examined 3 to 4 mo
      after the well was capped. Healthy coral communities were observed at all sites
      >20 km from the Macondo well, including seven sites previously visited in
      September 2009, where the corals and communities appeared unchanged. However, at
      one site 11 km southwest of the Macondo well, coral colonies presented widespread
      signs of stress, including varying degrees of tissue loss, sclerite enlargement,
      excess mucous production, bleached commensal ophiuroids, and covering by brown
      flocculent material (floc). On the basis of these criteria the level of impact to
      individual colonies was ranked from 0 (least impact) to 4 (greatest impact). Of
      the 43 corals imaged at that site, 46% exhibited evidence of impact on more than
      half of the colony, whereas nearly a quarter of all of the corals showed impact
      to >90% of the colony. Additionally, 53% of these corals' ophiuroid associates
      displayed abnormal color and/or attachment posture. Analysis of hopanoid
      petroleum biomarkers isolated from the floc provides strong evidence that this
      material contained oil from the Macondo well. The presence of recently damaged
      and deceased corals beneath the path of a previously documented plume emanating
      from the Macondo well provides compelling evidence that the oil impacted deep
      water ecosystems. Our findings underscore the unprecedented nature of the spill
      in terms of its magnitude, release at depth, and impact to deep-water ecosystems.

PMID- 22454496
TI  - Bruton's tyrosine kinase phosphorylates Toll-like receptor 3 to initiate
      antiviral response.
AB  - Toll-like receptor 3 (TLR3) mediates antiviral response by recognizing double
      stranded RNA. Its cytoplasmic domain is tyrosine phosphorylated upon ligand
      binding and initiates downstream signaling via the adapter TIR-containing adaptor
      inducing interferon-beta (TRIF). However, the kinase responsible for TLR3
      phosphorylation remains unknown. We show here that Bruton's tyrosine kinase (BTK)
      deficient macrophages failed to secrete inflammatory cytokines and IFN-beta upon
      TLR3 stimulation and were impaired in clearing intracellular dengue virus
      infection. Mutant mice were also less susceptible to d-galactosamine/p(I:C)
      induced sepsis. In the absence of BTK, TLR3-induced phosphoinositide 3-kinase
      (PI3K), AKT and MAPK signaling and activation of NFkappaB, IRF3, and AP-1
      transcription factors were all defective. We demonstrate that BTK directly
      phosphorylates TLR3 and in particular the critical Tyr759 residue. BTK point
      mutations that abrogate or led to constitutive kinase activity have opposite
      effects on TLR3 phosphorylation. Loss of BTK also compromises the formation of
      the downstream TRIF/receptor-interacting protein 1 (RIP1)/TBK1 complex. Thus, BTK
      plays a critical role in initiating TLR3 signaling.

PMID- 22454494
TI  - Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA
      barcode marker for Fungi.
AB  - Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second
      largest kingdom of eukaryotic life, by a multinational, multilaboratory
      consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used
      as the animal barcode was excluded as a potential marker, because it is difficult
      to amplify in fungi, often includes large introns, and can be insufficiently
      variable. Three subunits from the nuclear ribosomal RNA cistron were compared
      together with regions of three representative protein-coding genes (largest
      subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and
      minichromosome maintenance protein). Although the protein-coding gene regions
      often had a higher percent of correct identification compared with ribosomal
      markers, low PCR amplification and sequencing success eliminated them as
      candidates for a universal fungal barcode. Among the regions of the ribosomal
      cistron, the internal transcribed spacer (ITS) region has the highest probability
      of successful identification for the broadest range of fungi, with the most
      clearly defined barcode gap between inter- and intraspecific variation. The
      nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups,
      had superior species resolution in some taxonomic groups, such as the early
      diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior
      to the ITS. The nuclear ribosomal small subunit has poor species-level resolution
      in fungi. ITS will be formally proposed for adoption as the primary fungal
      barcode marker to the Consortium for the Barcode of Life, with the possibility
      that supplementary barcodes may be developed for particular narrowly
      circumscribed taxonomic groups.

PMID- 22454497
TI  - Transcriptional requirements of the distal heavy-strand promoter of mtDNA.
AB  - The heavy strand of mtDNA contains two promoters with nonoverlapping functions.
      The role of the minor heavy-strand promoter (HSP2) is controversial, because the
      promoter has been difficult to activate in an in vitro system. We have isolated
      HSP2 by excluding its interaction with the more powerful HSP1 promoter, and we
      find that it is transcribed efficiently by recombinant mtRNA polymerase and
      mitochondrial transcription factor B2. The mitochondrial transcription factor A
      is not required for initiation, but it has the ability to alternatively activate
      and repress the HSP2 transcriptional unit depending on the ratio between
      mitochondrial transcription factor A and other transcription factors. The
      positioning of transcriptional initiation agrees with our current understanding
      of HSP2 activity in vivo. Serial deletion of HSP2 shows that only proximal
      sequences are required. Several mutations, including the disruption of a
      polycytosine track upstream of the HSP2 initiation site, influence
      transcriptional activity. Transcription from HSP2 is also observed when HeLa cell
      mitochondrial extract is used as the source of mitochondrial polymerase, and this
      transcription is maintained when HSP2 is provided in proper spacing and context
      to the HSP1 promoter. Studies of the linked heavy-strand promoters show that they
      are differentially regulated by ATP dosage. We conclude that HSP2 is transcribed
      and has features that allow it to regulate mitochondrial mRNA synthesis.

PMID- 22454498
TI  - Genetic switchboard for synthetic biology applications.
AB  - A key next step in synthetic biology is to combine simple circuits into higher
      order systems. In this work, we expanded our synthetic riboregulation platform
      into a genetic switchboard that independently controls the expression of multiple
      genes in parallel. First, we designed and characterized riboregulator variants to
      complete the foundation of the genetic switchboard; then we constructed the
      switchboard sensor, a testing platform that reported on quorum-signaling
      molecules, DNA damage, iron starvation, and extracellular magnesium concentration
      in single cells. As a demonstration of the biotechnological potential of our
      synthetic device, we built a metabolism switchboard that regulated four metabolic
      genes, pgi, zwf, edd, and gnd, to control carbon flow through three Escherichia
      coli glucose-utilization pathways: the Embden-Meyerhof, Entner-Doudoroff, and
      pentose phosphate pathways. We provide direct evidence for switchboard-mediated
      shunting of metabolic flux by measuring mRNA levels of the riboregulated genes,
      shifts in the activities of the relevant enzymes and pathways, and targeted
      changes to the E. coli metabolome. The design, testing, and implementation of the
      genetic switchboard illustrate the successful construction of a higher-order
      system that can be used for a broad range of practical applications in synthetic
      biology and biotechnology.

PMID- 22454499
TI  - Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing
      NY-ESO-1 antigen in ovarian cancer and melanoma patients.
AB  - Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated
      antigens are currently being evaluated in clinical trials as cancer vaccines to
      induce tumor-specific immune responses that will improve clinical outcome. To
      test whether a diversified prime and boost regimen targeting NY-ESO-1 will result
      in clinical benefit, we conducted two parallel phase II clinical trials of
      recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations
      with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial
      ovarian cancer (EOC) patients with advanced disease who were at high risk for
      recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4(+) and
      CD8(+) T cells were induced in a high proportion of melanoma and EOC patients. In
      melanoma patients, objective response rate [complete and partial response
      (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%,
      amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The
      median PFS in the melanoma patients was 9 mo (range, 0-84 mo) and the median OS
      was 48 mo (range, 3-106 mo). In EOC patients, the median PFS was 21 mo (95% CI,
      16-29 mo), and median OS was 48 mo (CI, not estimable). CD8(+) T cells derived
      from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets.
      These data provide preliminary evidence of clinically meaningful benefit for
      diversified prime and boost recombinant pox-viral-based vaccines in melanoma and
      ovarian cancer and support further evaluation of this approach in these patient
      populations.

PMID- 22454501
TI  - Tumor initiating but differentiated luminal-like breast cancer cells are highly
      invasive in the absence of basal-like activity.
AB  - The majority of human breast cancers exhibit luminal epithelial differentiation.
      However, most aggressive behavior, including invasion and purported cancer stem
      cell activity, are considered characteristics of basal-like cells. We asked the
      following questions: Must luminal-like breast cancer cells become basal-like to
      initiate tumors or to invade? Could luminally differentiated cells within a
      basally initiated hierarchy also be tumorigenic? To answer these questions, we
      used rare and mutually exclusive lineage markers to isolate subsets of luminal
      like and basal-like cells from human breast tumors. We enriched for populations
      with or without prominent basal-like traits from individual tumors or single cell
      cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor
      cells with basal-like traits mimicked phenotypic and functional behavior
      associated with stem cells assessed by gene expression, mammosphere formation and
      lineage markers. Luminal-like cells without basal-like traits, surprisingly, were
      fully capable of initiating invasive tumors in NOD SCID gamma (NSG) mice. In
      fact, these phenotypically pure luminal-like cells generated larger and more
      invasive tumors than their basal-like counterparts. The tumorigenicity and
      invasive potential of the luminal-like cancer cells relied strongly on the
      expression of the gene GCNT1, which encodes a key glycosyltransferase controlling
      O-glycan branching. These findings demonstrate that basal-like cells, as defined
      currently, are not a requirement for breast tumor aggressiveness, and that within
      a single tumor there are multiple "stem-like" cells with tumorigenic potential
      casting some doubt on the hypothesis of hierarchical or differentiative loss of
      tumorigenicity.

PMID- 22454502
TI  - Distinct mechanism for long-term contrast adaptation.
AB  - To optimize perception, neurons in the visual system adapt to the current
      environment. What determines the durability of this plasticity? Longer exposures
      to an environment produce longer-lasting effects, which could be due to either
      (i) a single mechanism controlling adaptation that gains strength over time, or
      (ii) long-term mechanisms that become active after long-term exposure. Using
      recently developed technology, we tested adaptation durations an order of
      magnitude greater that those tested previously, and used a "deadaptation"
      procedure to reveal effects of a unique long-term mechanism in the longest
      adaptation periods. After 4 h of contrast adaptation, human observers were
      exposed to natural images for 15 min, which completely cancelled perceptual
      aftereffects of adaptation. Strikingly, during continued testing this
      deadaptation faded, and the original adaptation effects reappeared. This pattern
      strongly suggests that adaptation was maintained in a distinct long-term
      mechanism, whereas deadaptation affected a short-term mechanism.

PMID- 22454505
TI  - Selecting highly structure-specific antibodies using structured synthetic mimics
      of the cystine knot protein sclerostin.
AB  - Antibodies directed against specific regions of a protein have traditionally been
      raised against full proteins, protein domains or simple unstructured peptides,
      containing contiguous stretches of primary sequence. We have used a new approach
      of selecting antibodies against restrained peptides mimicking defined epitopes of
      the bone modulator protein sclerostin, which has been identified as a negative
      regulator of the Wnt pathway. For a fast exploration of activity defining
      epitopes, we produced a set of synthetic peptide constructs mimicking native
      sclerostin, in which intervening loops from the cystine-knot protein sclerostin
      were truncated and whose sequences were optimized for fast and productive
      refolding. We found that the second loop within the cystine knot could be
      replaced by unnatural sequences, both speeding up folding, and increasing yield.
      Subsequently, we used these constructs to pan the HuCAL phage display library for
      antibodies capable of binding the native protein, thereby restricting recognition
      to the desired epitope regions. It is shown that the antibodies that were
      obtained recognize a complex epitope in the protein that cannot be mimicked with
      linear peptides. Antibodies selected against peptides show similar recognition
      specificity and potency as compared with antibodies obtained from full-length
      recombinant protein.

PMID- 22454507
TI  - A mutation in VAPB that causes amyotrophic lateral sclerosis also causes a
      nuclear envelope defect.
AB  - A proline to serine mutation (P56S) in vesicle-associated membrane protein
      associated protein B and C (VAPB) causes an autosomal dominant form of
      amyotrophic lateral sclerosis (ALS). We show that the mutation also causes a
      nuclear envelope defect. Transport of nucleoporins (Nups) and emerin (EMD) to the
      nuclear envelope is blocked, resulting in their sequestration in dilated
      cytoplasmic membranes. Simultaneous overexpression of the FFAT motif (two
      phenylalanine residues in an acidic track) antagonizes the effect of mutant VAPB
      and restores transport to the nuclear envelope. VAPB function is required for
      transport to the nuclear envelope, with knockdown of endogenous VAPB
      recapitulating this phenotype. Moreover, we identified the compartment into which
      the Nups and EMD were sequestered as the endoplasmic reticulum (ER)-Golgi
      intermediate compartment (ERGIC), with nuclear envelope membrane proteins
      transiting to the ERGIC before VAPB-dependent retrograde transport to the nuclear
      envelope.

PMID- 22454508
TI  - The ubiquitin-like (UBX)-domain-containing protein Ubx2/Ubxd8 regulates lipid
      droplet homeostasis.
AB  - Lipid droplets (LDs) are central organelles for maintaining lipid homeostasis.
      However, how cells control the size and number of LDs remains largely unknown.
      Herein, we report that Ubx2, a UBX-domain-containing protein involved in
      endoplasmic reticulum (ER)-associated degradation, is crucial for LD maintenance.
      Ubx2 redistributes from the ER to LDs when LDs start to form and enlarge during
      diauxic shift and in the stationary phase. ubx2Delta cells contain abnormal
      numbers of LDs that are smaller than normal, and their triacylglycerol (TAG) is
      reduced to 50% of the normal level. Deletion of either the UBX or UBA domain in
      Ubx2 has no effect, but deletion of both causes LD phenotypes similar to that in
      ubx2Delta. The reduced level of TAG in ubx2Delta is probably the result of
      mislocalization of phospholipid:diacylglycerol acyltransferase (Lro1), one of the
      two TAG-synthesizing enzymes in yeast, which moves along the ER and distributes
      dynamically to the putative LD assembly sites abutting LDs. Thus, Ubx2 is
      important for the maintenance of cellular TAG homeostasis probably through Lro1.
      The mammalian Ubxd8 (also known as FAF2), when expressed in yeast, complements
      the defect of ubx2Delta, implying a functional conservation for these UBX-domain
      containing proteins in lipid homeostasis.

PMID- 22454506
TI  - Lung cancers diagnosed at annual CT screening: volume doubling times.
AB  - PURPOSE: To empirically address the distribution of the volume doubling time
      (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic
      (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP),
      first and foremost with respect to rates of tumor growth but also in terms of
      cell types. MATERIALS AND METHODS: All CT screenings in I-ELCAP from 1993 to 2009
      were performed according to HIPAA-compliant protocols approved by the
      institutional review boards of the collaborating institutions. All instances of
      first diagnosis of primary lung cancer after a negative screening result 7-18
      months earlier were identified, with symptom-prompted diagnoses included. Lesion
      diameter was calculated by using the measured length and width of each cancer at
      the time when the nodule was first identified for further work-up and at the time
      of the most recent prior screening, 7-18 months earlier. The length and width
      were measured a second time for each cancer, and the geometric mean of the two
      calculated diameters was used to calculate the VDT. The chi(2) statistic was used
      to compare the VDT distributions. RESULTS: The median VDT for 111 cancers was 98
      days (interquartile range, 108). For 56 (50%) cancers it was less than 100 days,
      and for three (3%) cancers it was more than 400 days. Adenocarcinoma was the most
      frequent cell type (50%), followed by squamous cell carcinoma (19%), small cell
      carcinoma (19%), and others (12%). Lung cancers manifesting as subsolid nodules
      had significantly longer VDTs than those manifesting as solid nodules (P <
      .0001). CONCLUSION: Lung cancers diagnosed in annual repeat rounds of CT
      screening, as manifest by the VDT and cell-type distributions, are similar to
      those diagnosed in the absence of screening.

PMID- 22454509
TI  - Macrophage migration inhibitory factor (MIF) promotes cell survival and
      proliferation of neural stem/progenitor cells.
AB  - In a previous study, we showed that murine dendritic cells (DCs) can increase the
      number of neural stem/progenitor cells (NSPCs) in vitro and in vivo. In the
      present study, we identified macrophage migration inhibitory factor (MIF) as a
      novel factor that can support the proliferation and/or survival of NSPCs in
      vitro. MIF is secreted by DCs and NSPCs, and its function in the normal brain
      remains largely unknown. It was previously shown that in macrophages, MIF binds
      to a CD74-CD44 complex. In the present study, we observed the expression of MIF
      receptors in mouse ganglionic-eminence-derived neurospheres using flow cytometry
      in vitro. We also found CD74 expression in the ganglionic eminence of E14 mouse
      brains, suggesting that MIF plays a physiological role in vivo. MIF increased the
      number of primary and secondary neurospheres. By contrast, retrovirally expressed
      MIF shRNA and MIF inhibitor (ISO-1) suppressed primary and secondary neurosphere
      formation, as well as cell proliferation. In the neurospheres, MIF knockdown by
      shRNA increased caspase 3/7 activity, and MIF increased the phosphorylation of
      Akt, Erk, AMPK and Stat3 (Ser727), as well as expression of Hes3 and Egfr, the
      products of which are known to support cell survival, proliferation and/or
      maintenance of NSPCs. MIF also acted as a chemoattractant for NSPCs. These
      results show that MIF can induce NSPC proliferation and maintenance by multiple
      signaling pathways acting synergistically, and it may be a potential therapeutic
      factor, capable of activating NSPC, for the treatment of degenerative brain
      disorders.

PMID- 22454510
TI  - The DSPII splice variant is crucial for desmosome-mediated adhesion in HaCaT
      keratinocytes.
AB  - Desmosomes are intercellular junctions specialised for strong adhesion that are
      prominent in the epidermis and heart muscle. Defective desmosomal function due to
      inherited mutations in the constitutive desmosomal gene desmoplakin (DSP) causes
      skin or heart disorders and in some instances both. Different mutations have
      different disease-causing molecular mechanisms as evidenced by the varying
      phenotypes resulting from mutations affecting different domains of the same
      protein, but the majority of these mechanisms remain to be determined. Here, we
      studied two mutations in DSP that lead to different dosages of the two major DSP
      splice variants, DSPI and DSPII, and compared their molecular mechanisms. One of
      the mutations results in total DSP haploinsufficiency and is associated with
      autosomal dominant striate palmoplantar keratoderma (PPK). The other leads to
      complete absence of DSPI and the minor isoform DSPIa but normal levels of DSPII,
      and is associated with autosomal recessive epidermolytic PPK, woolly hair and
      severe arrhythmogenic dilated cardiomyopathy. Using siRNA treatments to mimic
      these two mutations and additionally a DSPII-specific siRNA, we found striking
      differences between DSP isoforms with respect to keratinocyte adhesion upon
      cellular stress with DSPII being the key component in intermediate filament (IF)
      stability and desmosome-mediated adhesion. In addition, reduction in DSP
      expression reduced the amount of plakophilin 1, desmocollin (DSC) 2 and DSC3 with
      DSPI having a greater influence than DSPII on the expression levels of DSC3.
      These results suggest that the two major DSP splice variants are not completely
      redundant in function and that DSPII dosage is particularly important for
      desmosomal adhesion in the skin.

PMID- 22454511
TI  - Role of LRP1 in transport of CCN2 protein in chondrocytes.
AB  - Low-density lipoprotein receptor-related protein 1 (LRP1) is known to be a
      receptor for signal transmission and endocytosis. We have previously reported
      that LRP1 regulates WNT-beta-catenin and protein kinase C signaling in
      chondrocytes, represses the hypertrophy of chondrocytes during endochondral
      ossification and that LRP1 is colocalized with a ligand, CCN family member 2
      (CCN2; also known as connective tissue growth factor, CTGF), which conducts
      endochondral ossification, in chondrocytes. However, the role of LRP1 in the
      endocytic transport of CCN2 in chondrocytes is not yet understood. In the present
      study, we investigated the interaction between LRP1 and CCN2 during endocytic
      trafficking. Small interfering RNA (siRNA)-mediated knockdown of LRP1 in
      chondrocytic HCS-2/8 cells showed that the amount of exogenous CCN2 binding
      and/or incorporation was decreased in the LRP1 downregulated cells. Importantly,
      we observed that CCN2 internalization in chondrocytes was dependent on clathrin,
      and internalizated CCN2 was colocalized with an early or recycling endosome
      marker. Transcytosis of CCN2 through HCS-2/8 cells was confirmed by performing
      experiments with a trans-well apparatus, and the amount of transcytosed CCN2 was
      decreased by an LRP1 antagonist. These findings rule out possible leakage and
      confirm the crucial involvement of LRP1 during experimental transcytosis.
      Moreover, under hypoxic conditions that mimic the cartilaginous microenvironment,
      the level of LRP1 and the amount of transcytosed CCN2 increased, and these
      increases were neutralized by treatment with the LRP1 antagonist. The
      distribution of LRP1 and its antagonist in the growth plate in vivo was
      consistent with that of CCN2 in this tissue, which is produced by and transported
      by LRP1 from the chondrocytes in the prehypertrophic layer. These findings
      suggest that LRP1 mediates the transcytosis of CCN2, which might be a crucial
      event that determines the distribution of CCN2 in cartilage.

PMID- 22454512
TI  - MNK1 kinase activity is required for abscission.
AB  - MNK1 is a serine/threonine kinase identified as a target for MAP kinase pathways.
      Using chemical drug, kinase-dead expression or knockdown by RNA interference, we
      show that inhibition of MNK1 induces the formation of multinucleated cells, which
      can be rescued by expressing a form of MNK1 that is resistant to RNA
      interference. We found that the active human form of MNK1 localises to
      centrosomes, spindle microtubules and the midbody. Time-lapse recording of MNK1
      depleted cells displays cytokinesis defects, as daughter cells fuse back
      together. When MNK1 activity was inhibited, no microtubule defect at the midbody
      was detected, however, anchorage of the membrane vesicle at the midbody was
      impaired as lumenal GFP-positive vesicles did not accumulate at the midbody. At
      the molecular level, we found that centriolin localisation was impaired at the
      midbody in MNK1-depleted cells. As a consequence, endobrevin - a v-SNARE protein
      implicated in the abscission step - was not properly localised to the midbody.
      Altogether, our data show that MNK1 activity is required for abscission.

PMID- 22454513
TI  - Loss of Pnn expression results in mouse early embryonic lethality and cellular
      apoptosis through SRSF1-mediated alternative expression of Bcl-xS and ICAD.
AB  - Pinin (Pnn), a serine/arginine-rich (SR)-related protein, has been shown to play
      multiple roles within eukaryotic cells including cell-cell adhesion, cell
      migration, regulation of gene transcription, mRNA export and alternative
      splicing. In this study, an attempt to generate mice homozygously deficient in
      Pnn failed because of early embryonic lethality. To evaluate the effects of loss
      of Pnn expression on cell survival, RNA interference experiments were performed
      in MCF-7 cells. Depletion of Pnn resulted in cellular apoptosis and nuclear
      condensation. In addition, nuclear speckles were disrupted, and expression levels
      of SR proteins were diminished. RT-PCR analysis showed that alternative splicing
      patterns of SRSF1 as well as of apoptosis-related genes Bcl-x and ICAD were
      altered, and expression levels of Bim isoforms were modulated in Pnn-depleted
      cells. Cellular apoptosis induced by Pnn depletion was rescued by overexpression
      of SRSF1, which also restored generation of Bcl-xL and functionless ICAD. Pnn
      expression is, therefore, essential for survival of mouse embryos and the breast
      carcinoma cell line MCF-7. Moreover, Pnn depletion, modulated by SRSF1,
      determines cellular apoptosis through activation of the expression of pro
      apoptotic Bcl-xS transcripts.

PMID- 22454514
TI  - A role for protein phosphatase PP1gamma in SMN complex formation and subnuclear
      localization to Cajal bodies.
AB  - The spinal muscular atrophy (SMA) gene product SMN forms with gem-associated
      protein 2-8 (Gemin2-8) and unrip (also known as STRAP) the ubiquitous survival
      motor neuron (SMN) complex, which is required for the assembly of spliceosomal
      small nuclear ribonucleoproteins (snRNPs), their nuclear import and their
      localization to subnuclear domain Cajal bodies (CBs). The concentration of the
      SMN complex and snRNPs in CBs is reduced upon SMN deficiency in SMA cells.
      Subcellular localization of the SMN complex is regulated in a phosphorylation
      dependent manner and the precise mechanisms remain poorly understood. Using co
      immunoprecipitation in HeLa cell extracts and in vitro protein binding assays, we
      show here that the SMN complex and its component Gemin8 interact directly with
      protein phosphatase PP1gamma. Overexpression of Gemin8 in cells increases the
      number of CBs and results in targeting of PP1gamma to CBs. Moreover, depletion of
      PP1gamma by RNA interference enhances the localization of the SMN complex and
      snRNPs to CBs. Consequently, the interaction between SMN and Gemin8 increases in
      cytoplasmic and nuclear extracts of PP1gamma-depleted cells. Two-dimensional
      protein gel electrophoresis revealed that SMN is hyperphosphorylated in nuclear
      extracts of PP1gamma-depleted cells and expression of PP1gamma restores these
      isoforms. Notably, SMN deficiency in SMA leads to the aberrant subcellular
      localization of Gemin8 and PP1gamma in the atrophic skeletal muscles, suggesting
      that the function of PP1gamma is likely to be affected in disease. Our findings
      reveal a role of PP1gamma in the formation of the SMN complex and the maintenance
      of CB integrity. Finally, we propose Gemin8 interaction with PP1gamma as a target
      for therapeutic intervention in SMA.

PMID- 22454515
TI  - Human Mob1 proteins are required for cytokinesis by controlling microtubule
      stability.
AB  - The completion of cytokinesis requires abscission of the midbody, a microtubule
      rich cytoplasmic bridge that connects the daughter cells before their final
      separation. Although it has been established that both the midbody structure and
      membrane fusion are essential for abscission, the biochemical machinery and the
      cellular processes of abscission remain ill-defined. Here we report that human
      Mob1A and Mob1B proteins are involved in the regulation of abscission of the
      intercellular bridge. The Mob family is a group of highly conserved proteins in
      eukaryotes, described as binding partners as well as co-activators of protein
      kinases of the Ndr family, and as members of the Hippo pathway. We show that
      depletion of Mob1A and Mob1B by RNAi causes abscission failure as a consequence
      of hyper-stabilization of microtubules in the midbody region. Interestingly,
      depleting Mob1 also increases cell motility after cytokinesis, and induces
      prolonged centriole separation in G1 phase. In contrast, centrosomes fail to
      split when either Mob1A or Mob1B is overexpressed. Our findings indicate that
      human Mob1 proteins are involved in the regulation of microtubule stability at
      the midbody. We conclude that Mob1A and Mob1B are needed for cell abscission and
      centriole re-joining after telophase and cytokinesis.

PMID- 22454516
TI  - Functional analysis of parvin and different modes of IPP-complex assembly at
      integrin sites during Drosophila development.
AB  - Integrin-linked kinase (ILK), PINCH and parvin constitute the tripartite IPP
      complex that maintains the integrin-actin link at embryonic muscle attachment
      sites (MASs) in Drosophila. Here we showed that parvin null mutants in Drosophila
      exhibit defects in muscle adhesion, similar to ILK and PINCH mutants.
      Furthermore, the identical muscle phenotype of the triple mutant, which for the
      first time in any organism removed the entire IPP-complex function, genetically
      demonstrated that parvin, ILK and PINCH function synergistically. This is
      consistent with the tight localization of the tripartite complex at sites of
      integrin adhesion, namely MASs in the developing embryo and focal-contact-like
      structures in the wing epithelium. Parvin contains tandem unconventional calponin
      homology (CH) domains separated by a linker sequence, and a less-well conserved N
      terminal region. In vivo structure-function analysis revealed that all the
      domains are essential for parvin function, whereas recruitment at integrin
      adhesion sites is mediated by two localization signals: one located within the
      CH2 domain as previously reported, and a second novel signal within the CH1
      domain. Interestingly, this site is masked by the linker region between the two
      CH domains, suggesting a regulatory mechanism to control parvin localization.
      Finally, whereas in muscles only ILK controls the stability and localization of
      both PINCH and parvin, in the wing epithelium the three proteins mutually depend
      on each other. Thus molecular differences exist in the assembly properties of IPP
      complex in specific tissues during development, where differential modulation of
      the integrin connection to the cytoskeleton is required.

PMID- 22454517
TI  - The Ndc80 internal loop is required for recruitment of the Ska complex to
      establish end-on microtubule attachment to kinetochores.
AB  - The Ndc80 complex establishes end-on attachment of kinetochores to microtubules,
      which is essential for chromosome segregation. The Ndc80 subunit is characterized
      by an N-terminal region that binds directly to microtubules, and a long coiled
      coil region that interacts with Nuf2. A loop region in Ndc80 that generates a
      kink in the structure disrupts the long coiled-coil region but the exact function
      of this loop, has until now, not been clear. Here we show that this loop region
      is essential for end-on attachment of kinetochores to microtubules in human
      cells. Cells expressing loop mutants of Ndc80 are unable to align the
      chromosomes, and stable kinetochore fibers are absent. Through quantitative mass
      spectrometry and immunofluorescence we found that the binding of the spindle and
      kinetochore associated (Ska) complex depends on the loop region, explaining why
      end-on attachment is defective. This underscores the importance of the Ndc80 loop
      region in coordinating chromosome segregation through the recruitment of specific
      proteins to the kinetochore.

PMID- 22454518
TI  - Phosphoinositide specificity determines which cytohesins regulate beta1 integrin
      recycling.
AB  - Recycling of internalized integrins is a crucial step in adhesion remodeling and
      cell movement. Recently, we determined that the ADP-ribosylation factor-guanine
      nucleotide exchange factors (ARF-GEFs) cytohesin 2/ARNO and cytohesin 3/GRP1 have
      opposing effects on adhesion and stimulated beta1 integrin recycling even though
      they are very closely related proteins (80% sequence identity). We have now
      determined the sequence differences underlying the differential actions of
      cytohesin 2/ARNO and cytohesin 3/GRP1. We found that the ability of cytohesins to
      promote beta1 integrin recycling and adhesion depends upon the presence or
      absence of a key glycine residue in their pleckstrin homology (PH) domains. This
      glycine residue determines the phosphoinositide specificity and affinity of
      cytohesin PH domains. Switching the number of glycines in the PH domains of
      cytohesin 2 and cytohesin 3 is sufficient to reverse their effects on adhesion
      and spreading and to reverse their subcellular locations. Importantly, we also
      find that a mutant form of cytohesin 3/GRP1 that has three rather than two
      glycines in its PH domain rescues beta1 integrin recycling in cytohesin 2/ARNO
      knockdown cells. Conversely, a mutant form of cytohesin 2/ARNO with two glycines
      in its PH domain fails to rescue beta1 integrin recycling. Therefore, we conclude
      that phosphoinositide specificity is the sole functional difference that
      determines which cytohesin can promote integrin recycling.

PMID- 22454519
TI  - The translational repressor Cup is required for germ cell development in
      Drosophila.
AB  - In Drosophila, germ cell formation depends on inherited maternal factors
      localized in the posterior pole region of oocytes and early embryos, known as
      germ plasm. Here, we report that heterozygous cup mutant ovaries and embryos have
      reduced levels of Staufen (Stau), Oskar (Osk) and Vasa (Vas) proteins at the
      posterior pole. Moreover, we demonstrate that Cup interacts with Osk and Vas to
      ensure anchoring and/or maintenance of germ plasm particles at the posterior pole
      of oocytes and early embryos. Homozygous cup mutant embryos have a reduced number
      of germ cells, compared to heterozygous cup mutants, which, in turn, have fewer
      germ cells than wild-type embryos. In addition, we show that cup and osk interact
      genetically, because reducing cup copy number further decreases the total number
      of germ cells observed in heterozygous osk mutant embryos. Finally, we detected
      cup mRNA and protein within both early and late embryonic germ cells, suggesting
      a novel role of Cup during germ cell development in Drosophila.

PMID- 22454520
TI  - A novel regulatory mechanism links PLCgamma1 to PDK1.
AB  - 3-Phosphoinositide-dependent protein kinase-1 (PDK1) and phospholipase C
      (PLC)gamma1 are two key enzymes in signal transduction that control several
      intracellular processes. Despite the fact that PLCgamma1 has been investigated
      for several years, the mechanisms of activation of this enzyme are still not
      completely clear. Similarly, although PDK1 has been mostly investigated for its
      role in activation of Akt, a crucial enzyme in regulation of several cellular
      processes, it has become evident recently that the role of PDK1 in physiological
      and pathological conditions is not limited to Akt activation. Here we demonstrate
      that PDK1 regulates PLCgamma1 activation in a mechanism involving association of
      the two enzymes and modulation of PLCgamma1 tyrosine phosphorylation. We further
      show that this novel PDK1-PLCgamma1 pathway is important for cancer cell
      invasion. The identification of a PDK1-PLCgamma1 pathway reveals the existence of
      a previously undetected link between two of the most important enzymes in signal
      transduction. This is likely to have profound consequences for our understanding
      of several cellular functions that are dependent on phosphoinositides and
      controlled by PDK1 and PLCgamma1.

PMID- 22454521
TI  - Caveolar domain organization and trafficking is regulated by Abl kinases and
      mDia1.
AB  - The biology of caveolin-1 (Cav1)/caveolae is intimately linked to actin dynamics
      and adhesion receptors. Caveolar domains are organized in hierarchical levels of
      complexity from curved or flattened caveolae to large, higher-order caveolar
      rosettes. We report that stress fibers controlled by Abl kinases and mDia1
      determine the level of caveolar domain organization, which conditions the
      subsequent inward trafficking of caveolar domains induced upon loss of cell
      adhesion from the extracellular matrix. Abl-deficient cells have fewer stress
      fibers, a smaller pool of stress-fiber co-aligned Cav1 and increased clustering
      of Cav1/caveolae at the cell surface. Defective caveolar linkage to stress fibers
      prevents the formation of big caveolar rosettes upon loss of cell adhesion,
      correlating with a lack of inward trafficking. Live imaging of stress fibers and
      Cav1 showed that the actin-linked Cav1 pool loses its spatial organization in the
      absence of actin polymerization and is dragged and clustered by depolymerizing
      filaments. We identified mDia1 as the actin polymerization regulator downstream
      of Abl kinases that controls the stress-fiber-linked Cav1 pool. mDia1 knockdown
      results in Cav1/caveolae clustering and defective inward trafficking upon loss of
      cell adhesion. By contrast, cell elongation imposed by the excess of stress
      fibers induced by active mDia1 flattens caveolae. Furthermore, active mDia1
      rescues the actin co-aligned Cav1 pool and Cav1 inward trafficking upon loss of
      adhesion in Abl-deficient cells. Thus, caveolar domain organization and
      trafficking are tightly coupled to adhesive and stress fiber regulatory pathways.

PMID- 22454522
TI  - Fos plays an essential role in the upregulation of RANK expression in osteoclast
      precursors within the bone microenvironment.
AB  - Fos plays essential roles in the osteoclastic differentiation of precursor cells
      generated by colony-stimulating factor 1 (CSF-1) and receptor activator of NF
      kappaB ligand (RANKL; also known as tumor necrosis factor ligand superfamily
      member 11, Tnsf11). RANKL-deficient (RANKL(-/-)) mice and Fos(-/-) mice exhibit
      osteopetrosis due to an osteoclast deficiency. We previously reported that RANK
      positive osteoclast precursors are present in bone of RANKL(-/-) mice but not
      Fos(-/-) mice. Here we report the role of Fos in RANK expression in osteoclast
      precursors. Medullary thymic epithelial cells and intestinal antigen-sampling
      microfold cells have been shown to express RANK. High expression of RANK was
      observed in some epithelial cells in the thymic medulla and intestine but not in
      osteoclast precursors in Fos(-/-) mice. RANK mRNA and protein levels in bone were
      lower in Fos(-/-) mice than RANKL(-/-) mice, suggesting that Fos-regulated RANK
      expression is tissue specific. When wild-type bone marrow cells were inoculated
      into Fos(-/-) mice, RANK-positive cells appeared along bones. RANK expression in
      wild-type macrophages was upregulated by coculturing with RANKL(-/-) osteoblasts
      as well as wild-type osteoblasts, suggesting that cytokines other than RANKL
      expressed by osteoblasts upregulate RANK expression in osteoclast precursors. CSF
      1 receptor-positive cells were detected near CSF-1-expressing osteoblastic cells
      in bone in Fos(-/-) mice. CSF-1 upregulated RANK expression in wild-type
      macrophages but not Fos(-/-) macrophages. Overexpression of Fos in Fos(-/-)
      macrophages resulted in the upregulation of RANK expression. Overexpression of
      RANK in Fos(-/-) macrophages caused RANKL-induced signals, but failed to recover
      the RANKL-induced osteoclastogenesis. These results suggest that Fos plays
      essential roles in the upregulation of RANK expression in osteoclast precursors
      within the bone environment.

PMID- 22454523
TI  - Botulinum neurotoxin D-C uses synaptotagmin I and II as receptors, and human
      synaptotagmin II is not an effective receptor for type B, D-C and G toxins.
AB  - Botulinum neurotoxins (BoNTs) are classified into seven types (A-G), but multiple
      subtype and mosaic toxins exist. These subtype and mosaic toxins share a high
      sequence identity, and presumably the same receptors and substrates with their
      parental toxins. Here, we report that a mosaic toxin, type D-C (BoNT/D-C), uses
      different receptors from its parental toxin BoNT/C. BoNT/D-C, but not BoNT/C,
      binds directly to the luminal domains of synaptic vesicle proteins synaptotagmin
      (Syt) I and II, and requires expression of SytI/II to enter neurons. The SytII
      luminal fragment containing the toxin-binding site can block the entry of BoNT/D
      C into neurons and reduce its toxicity in vivo in mice. We also found that
      gangliosides increase binding of BoNT/D-C to SytI/II and enhance the ability of
      the SytII luminal fragment to block BoNT/D-C entry into neurons. These data
      establish SytI/II, in conjunction with gangliosides, as the receptors for BoNT/D
      C, and indicate that BoNT/D-C is functionally distinct from BoNT/C. We further
      found that BoNT/D-C recognizes the same binding site on SytI/II where BoNT/B and
      G also bind, but utilizes a receptor-binding interface that is distinct from
      BoNT/B and G. Finally, we also report that human and chimpanzee SytII has
      diminished binding and function as the receptor for BoNT/B, D-C and G owing to a
      single residue change from rodent SytII within the toxin binding site,
      potentially reducing the potency of these BoNTs in humans and chimpanzees.

PMID- 22454524
TI  - Plakoglobin-dependent regulation of keratinocyte apoptosis by Rnd3.
AB  - The human epidermis is a self-renewing, stratified epithelial tissue that
      provides the protective function of the skin. The principal cell type within the
      epidermis is the keratinocyte, and normal function of the epidermis requires that
      keratinocyte proliferation, differentiation and cell death be carefully
      controlled. There is clear evidence that signalling through adhesion receptors
      such as integrins and cadherins plays a key role in regulating epidermal
      function. Previous work has shown that Rho family GTPases regulate cadherin- and
      integrin-based adhesion structures and hence epidermal function. In this study,
      we show that a member of this family, Rnd3, regulates desmosomal cell-cell
      adhesion in that loss of Rnd3 expression leads to an increase in desmosomes at
      sites of cell-cell adhesion and altered colony morphology. Loss of Rnd3
      expression is also associated with resistance to cisplatin-mediated apoptosis in
      keratinocytes and this resistance is mediated through the desmosomal protein
      plakoglobin. We propose a novel plakoglobin-dependent role for Rnd3 in the
      regulation of keratinocyte cell death.

PMID- 22454525
TI  - MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by
      targeting Nodal.
AB  - Nodal is a member of the transforming growth factor-beta superfamily that plays
      crucial roles during embryogenesis. Recently, we have reported that Nodal
      inhibits trophoblast cell proliferation, migration and invasion, but induces
      apoptosis in the human placenta. In this study, we examined the regulation of
      Nodal by microRNAs. In silico analysis of Nodal 3'UTR revealed a potential
      binding site for miR-378a-5p. In luciferase reporter assays, we found that miR
      378a-5p suppressed the luciferase activity of a reporter plasmid containing Nodal
      3'UTR but this suppressive effect was completely abolished when the predicted
      target site was mutated. Western blot analysis showed that miR-378a-5p decreased
      whereas anti-miR-378a-5p increased Nodal protein levels. These results indicate
      that miR-378a-5p targets Nodal 3'UTR to repress its expression. Stable
      transfection of the miR-378a-5p precursor, mir-378a, into HTR8/SVneo cells
      enhanced cell survival, proliferation, migration and invasion. Transient
      transfection of mature miR-378a-5p mimic, and to a lesser extent, siRNA targeting
      Nodal, produced similar effects. However, anti-miR-378a-5p inhibited cell
      migration and invasion. In addition, overexpression of Nodal reversed the
      invasion-promoting effect of miR-378a-5p. Furthermore, miR-378a-5p enhanced,
      whereas anti-miR-378a-5p suppressed, the outgrowth and spreading of extravillous
      trophoblast cells in first trimester placental explants. Finally, miR-378a-5p was
      detected in human placenta throughout different stages of gestation and in
      preterm pregnancies, placental miR-378a-5p levels were lower in preeclamptic
      patients than in healthy controls. Taken together, these findings strongly
      suggest that miR-378a-5p plays an important role in human placental development
      by regulating trophoblast cell growth, survival, migration and invasion, and that
      miR-378a-5p exerts these effects, at least in part, through the suppression of
      Nodal expression.

PMID- 22454526
TI  - Nck and Cdc42 co-operate to recruit N-WASP to promote FcgammaR-mediated
      phagocytosis.
AB  - The adaptor protein Nck has been shown to link receptor ligation to actin-based
      signalling in a diverse range of cellular events, such as changes in cell
      morphology and motility. It has also been implicated in phagocytosis. However,
      its molecular role in controlling actin remodelling associated with phagocytic
      uptake remains to be clarified. Here, we show that Nck, which is recruited to
      phagocytic cups, is required for Fcgamma receptor (FcgammaR)- but not complement
      receptor 3 (CR3)-induced phagocytosis. Nck recruitment in response to FcgammaR
      ligation is mediated by the phosphorylation of tyrosine 282 and 298 in the ITAM
      motif in the cytoplasmic tail of the receptor. In the absence of FcgammaR
      phosphorylation, there is also no recruitment of N-WASP or Cdc42 to phagocytic
      cups. Nck promotes FcgammaR-mediated phagocytosis by recruiting N-WASP to
      phagocytic cups. Efficient phagocytosis, however, only occurs, if the CRIB domain
      of N-WASP can also interact with Cdc42. Our observations demonstrate that Nck and
      Cdc42 collaborate to stimulate N-WASP-dependent FcgammaR-mediated phagocytosis.

PMID- 22454527
TI  - Cdc14-dependent dephosphorylation of Inn1 contributes to Inn1-Cyk3 complex
      formation.
AB  - In Saccharomyces cerevisiae the Cdc14 phosphatase plays a well-established role
      in reverting phosphorylation events on substrates of the mitotic cyclin-dependent
      kinase (M-Cdk1), thereby promoting mitotic exit and downregulation of M-Cdk1
      activity. Cdc14 localizes at the site of cell cleavage after M-Cdk1 inactivation,
      suggesting that Cdc14 may perform a crucial, yet ill-defined, role during
      cytokinesis. Here, we identified Inn1, as a novel direct substrate of both M-Cdk1
      and Cdc14. Cdc14 colocalizes with Inn1 at the cell division site and interacts
      with the C-terminal proline-rich domain of Inn1 that mediates its binding to the
      SH3-domain-containing proteins Hof1 and Cyk3. We show that phosphorylation of
      Inn1 by Cdk1 partially perturbs the interaction of Inn1 with Cyk3 thereby
      reducing the levels of Cyk3 at the cell division site. We propose that Cdc14
      counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex
      formation and so promote cytokinesis.

PMID- 22454528
TI  - A cis-acting five-amino-acid motif controls targeting of ABCC2 to the apical
      plasma membrane domain.
AB  - ATP-binding cassette transporter isoform C2 (ABCC2) is exclusively targeted to
      the apical plasma membrane of polarized cells. Although apical localization of
      ABCC2 in hepatocytes is crucial for the biliary excretion of a variety of
      metabolites, the mechanism regulating its apical targeting is poorly understood.
      In the present study, an apical targeting signal was identified in the first
      cytoplasmic loop domain (CLD1) of ABCC2 in HepG2 cells. Overexpression of CLD1
      significantly disturbed the apical targeting of FLAG-ABCC2 in a competitive
      manner, suggesting the presence of a saturable sorting machinery in HepG2 cells.
      Next, deletion analysis identified a potential targeting sequence within a 20
      amino-acid long peptide (aa 272-291) of CLD1. Alanine scanning mutagenesis of
      this region in full-length ABCC2 further narrowed down the apical targeting
      determinant to five amino acids, S(283)QDAL(287). Of these, S(283) and L(287)
      were found to be conserved among vertebrate ABCC2 orthologs. Site-directed
      mutagenesis showed that both S(283) and L(287) were crucial for the targeting
      specificity of ABCC2. Introducing this apical targeting sequence into the
      corresponding region of ABCC1, an exclusively basolateral protein, caused the
      hybrid ABCC1 to partially localize in the apical membrane. Thus, the CLD1 of
      ABCC2 contains a novel apical sorting determinant, and a saturable sorting
      machinery is present in polarized HepG2 cells.

PMID- 22454529
TI  - The skeletal consequences of thyrotoxicosis.
AB  - Euthyroid status is essential for normal skeletal development and the maintenance
      of adult bone structure and strength. Established thyrotoxicosis has long been
      recognised as a cause of high bone turnover osteoporosis and fracture but more
      recent studies have suggested that subclinical hyperthyroidism and long-term
      suppressive doses of thyroxine (T4) may also result in decreased bone mineral
      density (BMD) and an increased risk of fragility fracture, particularly in
      postmenopausal women. Furthermore, large population studies of euthyroid
      individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set
      point at the upper end of the normal reference range is associated with reduced
      BMD and increased fracture susceptibility. Despite these findings, the cellular
      and molecular mechanisms of thyroid hormone action in bone remain controversial
      and incompletely understood. In this review, we discuss the role of thyroid
      hormones in bone and the skeletal consequences of hyperthyroidism.

PMID- 22454530
TI  - Evaluation of motility, membrane status and DNA integrity of frozen-thawed
      bottlenose dolphin (Tursiops truncatus) spermatozoa after sex-sorting and
      recryopreservation.
AB  - Artificial insemination (AI) with sex-sorted frozen-thawed spermatozoa has led to
      enhanced management of ex situ bottlenose dolphin populations. Extended distance
      of animals from the sorting facility can be overcome by the use of frozen-thawed,
      sorted and recryopreserved spermatozoa. Although one bottlenose dolphin calf had
      been born using sexed frozen-thawed spermatozoa derived from frozen semen, a
      critical evaluation of in vitro sperm quality is needed to justify the routine
      use of such samples in AI programs. Sperm motility parameters and plasma membrane
      integrity were influenced by stage of the sex-sorting process, sperm type (non
      sorted and sorted) and freezing method (straw and directional) (P<0.05). After
      recryopreservation, sorted spermatozoa frozen with the directional freezing
      method maintained higher (P<0.05) motility parameters over a 24-h incubation
      period compared to spermatozoa frozen using straws. Quality of sperm DNA of non
      sorted spermatozoa, as assessed by the sperm chromatin structure assay (SCSA),
      was high and remained unchanged throughout freeze-thawing and incubation
      processes. Though a possible interaction between Hoechst 33342 and the SCSA
      derived acridine orange was observed in stained and sorted samples, the
      proportion of sex-sorted, recryopreserved spermatozoa exhibiting denatured DNA
      was low (6.6+/-4.1%) at 6 h after the second thawing step and remained unchanged
      (P>0.05) at 24 h. The viability of sorted spermatozoa was higher (P<0.05) than
      that of non-sorted spermatozoa across all time points after recryopreservation.
      Collective results indicate that bottlenose dolphin spermatozoa undergoing
      cryopreservation, sorting and recryopreservation are of adequate quality for use
      in AI.

PMID- 22454531
TI  - Involvement of the transepithelial calcium transport disruption and the formation
      of epididymal stones in roosters.
AB  - Epididymal lithiasis is a dysfunction of unknown origin characterized by the
      formation of calcium stones into the lumen of efferent ductules of roosters.
      Affected animals present an imbalance in the hormonal responsive systems that
      regulate the expression of proteins involved in the transepithelial calcium
      transport, as TRPV6, CaBP-D28K, NCX1, and PMCA. Because the efferent ductules are
      the major site of fluid and calcium reabsorption in excurrent ducts, it was
      hypothesized that impairment in local calcium homeostasis would lead to
      lithiasis. To test this hypothesis, we addressed the expression of these proteins
      in the epididymal region of affected animals. The present study focused on the
      investigation of the occurrence, tissue distribution, and physiological impact of
      the transepithelial calcium transport in roosters under normal and pathological
      conditions. The results showed that affected roosters presented a significant
      increase in TRPV6 and CaBP-D28k levels, whereas NCX1 and PMCA were not changed.
      Such alterations were more conspicuous in the proximal efferent ductules, in
      which was also observed accumulation of calcium within the epithelial cells.
      These findings provided the first evidences for the involvement of alteration in
      the expression of proteins essential for calcium reabsorption as a plausible
      mechanism for the formation of calcium stones within efferent ductules.

PMID- 22454532
TI  - V-ATPase upregulation during early pregnancy: a possible link to establishment of
      an inflammatory response during preimplantation period of pregnancy.
AB  - Various mechanisms exist to prevent a potentially deleterious maternal immune
      response that results in compromising survival of semiallogeneic fetus. In
      pregnancy, there is a necessary early preimplantation inflammatory stage followed
      by a postimplantation anti-inflammatory stage. Thus, there is a biphasic 'immune
      response' observed during the course of pregnancy. We provide the evidence that
      capacitation of sperm induced the expression of a2 isoform of V-ATPase (ATP6V0A2
      referred to as a2V), leukemia inhibitory factor (Lif), Il1b, and Tnf in the
      sperm. Capacitated sperm also released cleaved N-terminal domain of a2V-ATPase
      (a2NTD), which upregulates the gene expression of Lif, Il1b, Tnf, and monocyte
      chemotactic protein-1 (Ccl2 (Mcp1)) in the uterus. Unfertilized eggs had low a2V
      expression, but after fertilization, the expression of a2V increased in zygotes.
      This increased level of a2V expression was maintained in preimplantation embryos.
      Seminal plasma was necessary for upregulation of a2V expression in
      preimplantation embryos, as mating with seminal vesicle-deficient males failed to
      elicit an increase in a2V expression in preimplantation embryos. The infiltration
      of macrophages into the uterus was significantly increased after insemination of
      both sperm and seminal plasma during the preimplantation period of pregnancy.
      This dynamic infiltration into the uterus corresponded with the uterine a2V
      expression through the induction of Ccl2 expression. Furthermore, the
      polarization ratio of M1:M2 (pro-inflammatory/anti-inflammatory) macrophages in
      the uterus fluctuated from a ratio of 1.60 (day 1) to 1.45 (day 4) when female
      mice were inseminated with both sperm and seminal plasma. These data provide
      evidence that exposure to semen may initiate an inflammatory milieu by inducing
      a2V and cytokine/chemokine expression, which triggers the influx of macrophages
      into the preimplantation uterus during the onset of pregnancy and ultimately
      leads to successful pregnancy outcome.

PMID- 22454533
TI  - The role of micro-RNAs in the female reproductive tract.
AB  - Proper development and function of the female reproductive tract are essential
      for successful reproduction. Regulation of the differentiated functions of the
      organs that make up the female reproductive tract is well established to occur at
      multiple levels including transcription, translation, and posttranslational
      modifications. Micro-RNA (miRNA)-mediated posttranscriptional gene regulation has
      emerged as a fundamental mechanism controlling normal tissue development and
      function. Emerging evidence indicates that miRNAs are expressed within the organs
      of the female reproductive tract where they function to regulate cellular
      pathways necessary for proper function of these organs. In this review, the
      functional significance of miRNAs in the development and function of the organs
      of the female reproductive tract is discussed. Initial discussion focuses on the
      role of miRNAs in the development of the organs of the female reproductive tract
      highlighting recent studies that clearly demonstrate that mice with disrupted
      Dicer1 expression are sterile, fail to develop uterine glands, and have muted
      estrogen responsiveness. Next, emphasis moves to discussion on our current
      knowledge on the characterization of miRNA expression in each of the organs of
      the female reproductive tract. When possible, information is presented and
      discussed with respect to regulation, function, and/or functional targets of
      these miRNA within each specific organ of the female reproductive tract.

PMID- 22454534
TI  - Morphine activates the E twenty six-like transcription factor-1/serum response
      factor pathway via extracellular signal-regulated kinases 1/2 in F11 cells
      derived from dorsal root ganglia neurons.
AB  - Morphine-induced signaling via opioid receptors (ORs) in dorsal root ganglia
      (DRG) neurons, the spinal cord, and various brain regions has been shown to
      modulate gene activity. Hitherto, little attention has been paid to extracellular
      signal-regulated kinases-1/2 (ERK-1/2)-mediated activation of the serum response
      factor (SRF) and ternary complex factors (TCFs) such as the E twenty six-like
      transcription factor-1 (ELK-1) in this context. Using TCF/SRF-dependent reporter
      gene constructs, a specific ERK-1/2 inhibitor and a dominant-negative ELK-1
      mutant, we show herein that morphine activates ELK-1 via ERK-1/2 in DRG-derived
      F11 cells endogenously expressing MU and delta ORs. Previous studies with glioma
      cell lines such as NG108-15 cells attributed morphine-induced gene expression to
      the activation of the cAMP-responsive element binding protein (CREB). Thus, we
      also analyzed morphine-dependent activation of CREB in F11 and NG108-15 cells. In
      contrast to the CREB stimulation found in NG108-15 cells, we observed an
      inhibitory effect of morphine in F11 cells, indicating cell type-specific
      regulation of CREB by morphine. To obtain data about putative target genes of
      morphine-induced ELK-1/SRF activation, we analyzed mRNA levels of 15 ELK-1/SRF
      dependent genes in cultured rat DRG neurons and F11 cells. We identified the
      early growth response protein-4 (EGR-4) as the strongest up-regulated gene in
      both cell types and observed ELK-1 activity-dependent activation of an EGR-4
      driven reporter in F11 cells. Overall, we reveal an important role of ELK-1 for
      morphine-dependent gene induction in DRG-derived cells and propose that ELK-1 and
      EGR-4 contribute to the effects of morphine on neuronal plasticity.

PMID- 22454535
TI  - Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on
      the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032).
AB  - Vemurafenib [N-(3-{[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl}
      2,4-difluorophenyl)propane-1-sulfonamide(PLX4032)] is a novel small-molecule BRAF
      inhibitor, recently approved by the Food and Drug Administration for the
      treatment of patients with metastatic melanoma with a BRAF(V600E) mutation. The
      objective of this study was to investigate the role of P-glycoprotein (P-gp) and
      breast cancer resistance protein (BCRP) in the distribution of vemurafenib to the
      central nervous system. In vitro studies conducted in transfected Madin-Darby
      canine kidney II cells show that the intracellular accumulation of vemurafenib is
      significantly restricted because of active efflux by P-gp and BCRP. Bidirectional
      flux studies indicated greater transport in the basolateral-to-apical direction
      than the apical-to-basolateral direction because of active efflux by P-gp and
      BCRP. The selective P-gp and BCRP inhibitors zosuquidar and (3S,6S,12aS)
      1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4
      dioxopyrazino(1',2':1,6)pyrido(3,4-b)indole-3-propanoic acid-1,1-dimethylethyl
      ester (Ko143) were able to restore the intracellular accumulation and
      bidirectional net flux of vemurafenib. The in vivo studies revealed that the
      brain distribution coefficient (area under the concentration time profile of
      brain/area under the concentration time profile of plasma) of vemurafenib was
      0.004 in wild-type mice. The steady-state brain-to-plasma ratio of vemurafenib
      was 0.035 +/- 0.009 in Mdr1a/b(-/-) mice, 0.009 +/- 0.006 in Bcrp1(-/-) mice, and
      1.00 +/- 0.19 in Mdr1a/b(-/-)Bcrp1(-/-) mice compared with 0.012 +/- 0.004 in
      wild-type mice. These data indicate that the brain distribution of vemurafenib is
      severely restricted at the blood-brain barrier because of active efflux by both P
      gp and BCRP. This finding has important clinical significance given the ongoing
      trials examining the efficacy of vemurafenib in brain metastases of melanoma.

PMID- 22454536
TI  - The ubiquitous hammerhead ribozyme.
AB  - The hammerhead ribozyme is a small catalytic RNA motif capable of endonucleolytic
      (self-) cleavage. It is composed of a catalytic core of conserved nucleotides
      flanked by three helices, two of which form essential tertiary interactions for
      fast self-scission under physiological conditions. Originally discovered in
      subviral plant pathogens, its presence in several eukaryotic genomes has been
      reported since. More recently, this catalytic RNA motif has been shown to reside
      in a large number of genomes. We review the different approaches in discovering
      these new hammerhead ribozyme sequences and discuss possible biological functions
      of the genomic motifs.

PMID- 22454537
TI  - The functional Hfq-binding module of bacterial sRNAs consists of a double or
      single hairpin preceded by a U-rich sequence and followed by a 3' poly(U) tail.
AB  - Hfq-dependent sRNAs contain, at least, an mRNA base-pairing region, an Hfq
      binding site, and a Rho-independent terminator. Recently, we found that the
      terminator poly(U) of Escherichia coli sRNAs is essential for Hfq binding and
      therefore for riboregulation. In this study, we tried to identify additional
      components within Hfq-binding sRNAs required for efficient Hfq binding by using
      SgrS as a model. We demonstrate by mutational and biochemical studies that an
      internal hairpin and an immediately upstream U-rich sequence also are required
      for efficient Hfq binding. We propose that the functional Hfq-binding module of
      SgrS consists of an internal hairpin preceded by a U-rich sequence and a Rho
      independent terminator with a long poly(U) tail. We also show that the Rho
      independent terminator alone can act as a functional Hfq-binding module when it
      is preceded by an internal U-rich sequence. The 3' region of most known sRNAs
      share the features corresponding to either a double- or single-hairpin-type Hfq
      binding module. We also demonstrate that increasing the spacing between the base
      pairing region and the Hfq-binding module reduces or impairs the silencing
      ability. These findings allowed us to design synthetic Hfq-binding sRNAs to
      target desired mRNAs.

PMID- 22454538
TI  - Alternative splicing networks regulated by signaling in human T cells.
AB  - The formation and execution of a productive immune response requires the
      maturation of competent T cells and a robust change in cellular activity upon
      antigen challenge. Such changes in cellular function depend on regulated
      alterations to protein expression. Previous research has focused on defining
      transcriptional changes that regulate protein expression during T-cell maturation
      and antigen stimulation. Here, we globally analyze another critical process in
      gene regulation during T-cell stimulation, alternative splicing. Specifically, we
      use RNA-seq profiling to identify 178 exons in 168 genes that exhibit robust
      changes in inclusion in response to stimulation of a human T-cell line.
      Supporting an important role for the global coordination of alternative splicing
      following T-cell stimulation, these signal-responsive exons are significantly
      enriched in genes with functional annotations specifically related to immune
      response. The vast majority of these genes also exhibit differential alternative
      splicing between naive and activated primary T cells. Comparison of the
      responsiveness of splicing to various stimuli in the cultured and primary T cells
      further reveals at least three distinct networks of signal-induced alternative
      splicing events. Importantly, we find that each regulatory network is
      specifically associated with distinct sequence features, suggesting that they are
      controlled by independent regulatory mechanisms. These results thus provide a
      basis for elucidating mechanisms of signal pathway-specific regulation of
      alternative splicing during T-cell stimulation.

PMID- 22454539
TI  - Platform-independent and label-free quantitation of proteomic data using MS1
      extracted ion chromatograms in skyline: application to protein acetylation and
      phosphorylation.
AB  - Despite advances in metabolic and postmetabolic labeling methods for quantitative
      proteomics, there remains a need for improved label-free approaches. This need is
      particularly pressing for workflows that incorporate affinity enrichment at the
      peptide level, where isobaric chemical labels such as isobaric tags for relative
      and absolute quantitation and tandem mass tags may prove problematic or where
      stable isotope labeling with amino acids in cell culture labeling cannot be
      readily applied. Skyline is a freely available, open source software tool for
      quantitative data processing and proteomic analysis. We expanded the capabilities
      of Skyline to process ion intensity chromatograms of peptide analytes from full
      scan mass spectral data (MS1) acquired during HPLC MS/MS proteomic experiments.
      Moreover, unlike existing programs, Skyline MS1 filtering can be used with mass
      spectrometers from four major vendors, which allows results to be compared
      directly across laboratories. The new quantitative and graphical tools now
      available in Skyline specifically support interrogation of multiple acquisitions
      for MS1 filtering, including visual inspection of peak picking and both automated
      and manual integration, key features often lacking in existing software. In
      addition, Skyline MS1 filtering displays retention time indicators from
      underlying MS/MS data contained within the spectral library to ensure proper peak
      selection. The modular structure of Skyline also provides well defined,
      customizable data reports and thus allows users to directly connect to existing
      statistical programs for post hoc data analysis. To demonstrate the utility of
      the MS1 filtering approach, we have carried out experiments on several MS
      platforms and have specifically examined the performance of this method to
      quantify two important post-translational modifications: acetylation and
      phosphorylation, in peptide-centric affinity workflows of increasing complexity
      using mouse and human models.

PMID- 22454541
TI  - Living with radiation.

PMID- 22454540
TI  - Proteomic cornerstones of hematopoietic stem cell differentiation: distinct
      signatures of multipotent progenitors and myeloid committed cells.
AB  - Regenerative tissues such as the skin epidermis, the intestinal mucosa or the
      hematopoietic system are organized in a hierarchical manner with stem cells
      building the top of this hierarchy. Somatic stem cells harbor the highest self
      renewal activity and generate a series of multipotent progenitors which
      differentiate into lineage committed progenitors and subsequently mature cells.
      In this report, we applied an in-depth quantitative proteomic approach to analyze
      and compare the full proteomes of ex vivo isolated and FACS-sorted populations
      highly enriched for either multipotent hematopoietic stem/progenitor cells
      (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) or myeloid committed precursors (Lin(neg)Sca-1(
      )c-Kit(+)). By employing stable isotope dimethyl labeling and high-resolution
      mass spectrometry, more than 5000 proteins were quantified. From biological
      triplicate experiments subjected to rigorous statistical evaluation, 893 proteins
      were found differentially expressed between multipotent and myeloid committed
      cells. The differential protein content in these cell populations points to a
      distinct structural organization of the cytoskeleton including remodeling
      activity. In addition, we found a marked difference in the expression of
      metabolic enzymes, including a clear shift of specific protein isoforms of the
      glycolytic pathway. Proteins involved in translation showed a collective higher
      expression in myeloid progenitors, indicating an increased translational
      activity. Strikingly, the data uncover a unique signature related to immune
      defense mechanisms, centering on the RIG-I and type-1 interferon response
      systems, which are installed in multipotent progenitors but not evident in
      myeloid committed cells. This suggests that specific, and so far unrecognized,
      mechanisms protect these immature cells before they mature. In conclusion, this
      study indicates that the transition of hematopoietic stem/progenitors toward
      myeloid commitment is accompanied by a profound change in processing of cellular
      resources, adding novel insights into the molecular mechanisms at the interface
      between multipotency and lineage commitment.

PMID- 22454543
TI  - Alphafetoprotein in the Dutch External Quality Assurance programme: a need for
      improvement.
AB  - BACKGROUND: Elevated alphafetoprotein (AFP) concentrations may result from a
      variety of clinical conditions, but their role as an important tumour marker has
      been well established. There may be differences in AFP values due to laboratories
      using different methods, even though most methods have been calibrated with the
      same international standard (WHO IS 72/225). Therefore it is important to know
      the analytical performance of the various methods in relation to the analytical
      requirements for AFP measurement. METHODS: Annually, from January 2005 to July
      2010, the results were analysed from the 65-75 laboratories that took part in the
      AFP survey of the External Quality Assurance programme of the Foundation Quality
      Control Medical Laboratories (the SKML/Binding Analysis) in the Netherlands.
      RESULTS: The Elecsys/Modular (36%) and the Immulite 2000/2500 (29%) are the
      methods used most. The methods show, on average, up to 15% positive and 12%
      negative bias, compared with the all-laboratory trimmed mean. Of the laboratories
      using the Immulite or the Elecsys/Modular analyser, over 70% show sufficient
      analytical performance to meet the Fraser criterion for method imprecision. Of
      the laboratories using a different method, over 50% do not meet this criterion.
      CONCLUSIONS: AFP immunoassays suffer from method bias, even though all methods
      have been calibrated with the same international standard. Some of the methods
      used show insufficient performance.

PMID- 22454544
TI  - Identification of a macro-alkaline phosphatase complex in a patient with
      inflammatory bowel disease.
AB  - We report the rare finding of a macro-alkaline phosphatase (macroALP) complex in
      a patient with a previously unexplained raised alkaline phosphatase activity. The
      clinical symptoms were persistent, daily diarrhoea for two months with blood in
      the stool. The patient was subsequently diagnosed with inflammatory bowel
      disease, specifically ulcerative colitis, following a rectal biopsy and
      colonoscopy. Two cases of macroALP associated with ulcerative colitis have been
      reported before, suggesting there could be an increased prevalence of macroALP in
      these patients.

PMID- 22454545
TI  - Exposure of alveolar macrophages to polybrominated diphenyl ethers suppresses the
      release of pro-inflammatory products in vitro.
AB  - Inhalation of chemical pollutants has been associated with a reduced immune
      response in humans. Inhalation of dust is a major route of exposure for one
      endocrine-disrupting chemical and suspected xenoestrogen, polybrominated diphenyl
      ethers (PBDEs); however, the impact of PBDEs on immune function is unclear. The
      objective of this study was to investigate the action of PBDEs on cytokine and
      eicosanoid release by alveolar macrophages and determine whether the effects are
      mediated via the estrogen receptor. The production of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, IL-1beta, IL-10 and prostaglandin E(2) (PGE(2)) by
      porcine alveolar macrophages exposed to different concentrations of the
      pentabrominated diphenyl ether mixture, DE-71, were measured; cells were also
      exposed to varying concentrations of 17beta-estradiol and the selective estrogen
      receptor-modulating agent, tamoxifen. Cells exposed to PBDEs released
      significantly less pro-inflammatory cytokines (TNF-alpha and IL-6) and PGE(2)
      compared with controls; IL-1beta and IL-10 were not detected in the culture
      medium. Cells exposed to 17beta-estradiol released significantly less TNF-alpha
      compared with controls, an effect that was reversed by the addition of tamoxifen;
      tamoxifen had no effect on the inhibition of TNF-alpha release by PBDEs. Although
      the suppression of TNF-alpha with DE-71 was similar to that of estrogen, the
      inhibitory effects of DE-71 were not found to be dependent on the estrogen
      receptor. Findings of this study suggest that chronic exposure to PBDEs
      suppressed innate immunity in vitro. Whether the immunosuppressant effects of
      PBDEs occur in vivo, remains to be determined.

PMID- 22454546
TI  - Fat intake leads to differential response of rat adipocytes to glucose, insulin
      and ascorbic acid.
AB  - Antioxidant-based treatments have emerged as novel and interesting approaches to
      counteract fat accumulation in obesity and associated metabolic disturbances.
      Adipocytes from rats that were fed on chow or high-fat diet (HFD) for 50 d were
      isolated (primary adipocytes) and incubated (72 h) on low (LG; 5.6 mmol/L) or
      high (HG; 25 mmol/L) glucose levels, in the presence or absence of 1.6 nmol/L
      insulin and 200 MUmol/L vitamin C (VC). Adipocytes from HFD-fed animals presented
      lower insulin-induced glucose uptake, lower lactate and glycerol release, and
      lower insulin-induced secretion of some adipokines as compared with controls. HG
      treatment restored the blunted response to insulin regarding apelin secretion in
      adipocytes from HFD-fed rats. VC treatment inhibited the levels of nearly all
      variables, irrespective of the adipocytes' dietary origin. The HG treatment
      reduced adipocyte viability, and VC protected from this toxic effect, although
      more drastically in control adipocytes. Summing up, in vivo chow or HFD intake
      determines a differential response to insulin and glucose treatments that appears
      to be dependent on the insulin-resistance status of the adipocytes, while VC
      modifies some responses from adipocytes independently of the previous dietary
      intake of the animals.

PMID- 22454547
TI  - Early and mid-term results of a prospective observational study comparing
      emergency endovascular aneurysm repair with open surgery in both ruptured and
      unruptured acute abdominal aortic aneurysms.
AB  - The aim of the paper is to prospectively describe early and mid-term outcomes for
      emergency endovascular aneurysm repair (eEVAR) versus open surgery in acute
      abdominal aortic aneurysms (aAAAs), both unruptured (symptomatic) and ruptured.
      We enrolled all consecutive patients treated for aAAA at our center between April
      2002 and April 2008. The main outcome parameters were 30-day, 6- and 12-month
      mortality (all-cause and aneurysm-related). Two hundred forty patients were
      enrolled in the study. In the unruptured aAAA group (n = 111), 47 (42%) underwent
      eEVAR. The 30-day, 6- and 12-month mortality rates were 6, 13 and 15% in the
      eEVAR group versus 11% (NS), 13% (NS) and 16% (NS) in the open group,
      respectively. In the ruptured aAAA group (n = 129), 25 (19%) underwent eEVAR
      (mortality rates: 20, 28 and 36%, respectively) compared with 104 (81%) patients
      who underwent open surgery (mortality rates: 45% (P = 0.021), 60% (P = 0.004) and
      63% (P = 0.014), respectively). In conclusion, the present study showed a reduced
      30-day, 6- and 12-month mortality of eEVAR compared with open surgery in all
      patients with aAAA, mainly due to a lower mortality in the ruptured aAAA group.
      Late aneurysm-related mortality occurred only in the eEVAR group.

PMID- 22454548
TI  - The use of heparin in patients with ruptured abdominal aortic aneurysms.
AB  - The use of systemic heparin in patients with ruptured abdominal aortic aneurysms
      (rAAAs) remains a contentious issue with no clear guidelines. This review reports
      the current understanding, at a molecular and clinical level, of the possible
      benefits and risks of heparin in emergency aneurysm repair (both open and
      endovascular). MEDLINE, EMBASE, AMED, SCOPUS, CINAHL and Cochrane Library were
      searched for all articles containing the keywords 'rupture', 'abdominal',
      'aneurysm' and 'heparin'. Current experience, indications and outcomes were
      analyzed. Articles were searched for both endovascular and open repair of AAAs. A
      total of eight studies were included for analysis in the systematic review. Of
      these, only one paper focused specifically on heparin use in open repair of
      ruptures and suggested a benefit. Of the remaining seven, two were self-reporting
      retrospective studies assessing individual surgeons' practice, one was a case
      report and the remaining four included mention of heparin use but with no outcome
      data. The evidence available suggests that a pro-coagulable state exists in
      rAAAs. This may be responsible for the morbidity and mortality postprocedure,
      which arises predominantly from multiple organ failure and cardiac compromise
      rather than outright hemorrhage. This diathesis may respond well to heparin
      administration, suggesting that heparin administration in ruptured aneurysms is
      appropriate.

PMID- 22454549
TI  - Balloon-expandable stent deformation during deployment into the iliac artery: a
      procedural complication managed conservatively.
AB  - The management of aortoiliac insufficiency has been improved considerably since
      the introduction of balloon-expandable stents in 1991. Although numerous studies
      have shown the safety and efficacy of balloon-expandable iliac artery stent
      placement, the procedure is not without potential complication. We report here a
      very unusual case of iliac artery stenting being complicated by deformation and
      elongation of the stent following balloon rupture at initial deployment with
      retention of the distal balloon marker and our successful approach to subsequent
      management with combined acetylsalicylic acid and clopidogrel. In conclusion,
      this conservative approach may be an alternative treatment of a partially
      deployed aortoiliac stent with a retained foreign body when further intervention
      is considered to be of high risk.

PMID- 22454550
TI  - Aripiprazole vs placebo for schizophrenia.

PMID- 22454551
TI  - Repeat chlamydia testing across a New Zealand district: 3 years of laboratory
      data.
AB  - OBJECTIVES: To investigate the impact of repeat chlamydia testing on annual
      population coverage estimates and to examine repeat testing patterns in a New
      Zealand district with high chlamydia testing rates. METHODS: Chlamydia testing
      data for 15-44-year-old men and women in a single New Zealand district during
      February 2008 to January 2011 were analysed. Annual coverage of testing was
      estimated in two ways, using the number of tests and the number of individuals as
      the numerator. Rates of repeat testing were calculated using survival analysis.
      RESULTS: There were 73 879 tests (12 251 men, 61 628 women) from 41 342
      individuals (8437 men, 32 905 women) during 3 years. Coverage estimates in 2010
      using the number of individuals as the numerator were 17% lower for men and 26%
      lower for women than when the number of tests was used (5.9% vs 4.9% for men and
      28.7% vs 21.2% for women). The rate of repeat testing was 16.9 per 100 person
      years among men (95% CI 16.2 to 17.7) and 31.6 among women (95% CI 31.1 to 32.2).
      Rates of repeat testing were higher among women, in younger age groups and
      following a positive rather than a negative baseline test (p<0.001). CONCLUSION:
      Relatively high rates of repeat testing were observed among young women in
      Waikato district during 2008 to 2010. Estimates of population coverage by test
      for this group therefore considerably overestimate individual coverage. The
      findings will inform discussions about improving surveillance to capture more
      accurate chlamydia testing coverage rates in New Zealand.

PMID- 22454552
TI  - Shifts in plasmon resonance due to charging of a nanodisk array in argon plasma.
AB  - A method for generating charge-induced plasmonic shifts, using argon plasma to
      charge nanoparticle arrays, is presented. Particles develop a negative charge,
      due to enhanced collisions with high-temperature electrons, in low-temperature
      plasmas. The negative charge generated causes a blue shift in the localized
      surface plasmon resonance. The dynamics of the shift were recorded and discussed.
      This effect could be used as a real-time method for studying the dynamics for
      charging in plasma.

PMID- 22454553
TI  - The electronic and optical properties of Eu/Si-codoped anatase TiO(2)
      photocatalyst.
AB  - The electronic and optical properties of Eu/Si-codoped anatase TiO(2) are
      investigated using the density functional theory. The calculated results show
      that the synergistic effects of Eu/Si codoping can effectively extend the optical
      absorption edge, which can lead to higher visible-light photocatalytic activities
      than pure anatase TiO(2). To verify the reliability of our calculated results,
      nanocrystalline Eu/Si-codoped TiO(2) is prepared by a sol-gel-solvothermal
      method, and the experimental results also indicate that the codoping sample
      exhibits better absorption performance and higher photocatalytic activities than
      pure TiO(2).

PMID- 22454554
TI  - New class of biodegradable polymers formed from reactions of an inorganic
      functional group.
AB  - Although numerous small molecules have been synthesized with sulfenamide bonds
      (R(2)N-SR), this is the first report of the synthesis of polysulfenamides. These
      polymers are readily synthesized at room temperature using secondary diamines and
      dithiosuccinimides. The dithiosuccinimides were readily synthesized in one step
      by the reaction of dithiols such as HS(CH(2))(6)SH with N-chlorosuccinimide. The
      resulting dithiosuccinimides were either recrystallized or readily purified by
      chromatography on silica gel and required no special handling. The conversions of
      polymerization ranged from 95 to 98%, and the molecular weights of the polymer
      reached as high as 6,300 g mol(-1). The sulfenamide bond was very stable in
      organic solvents, and no degradation was observed under atmospheric conditions in
      C(6)D(6) for 30 days. In contrast, the sulfenamide bond readily decomposed in
      less than 12 h in D(2)O. Polysulfenamides were fabricated into micron-sized
      particles loaded with dye and endocytosed into JAWSII immature dendritic and
      HEK293 cells. Polysulfenamides represent a new class of polymers that are readily
      synthesized, stable in aprotic solvents, and readily degrade in water.

PMID- 22454555
TI  - Pancreaticopleural fistula: revisited.
AB  - Pancreaticopleural fistula is a rare complication of acute and chronic
      pancreatitis. This usually presents with chest symptoms due to pleural effusion,
      pleural pseudocyst, or mediastinal pseudocyst. Diagnosis requires a high index of
      clinical suspicion in patients who develop alcohol-induced pancreatitis and
      present with pleural effusion which is recurrent or persistent. Analysis of
      pleural fluid for raised amylase will confirm the diagnosis and investigations
      like CT. Endoscopic retrograde cholangiopancreaticography (ECRP) or magnetic
      resonance cholangiopancreaticography (MRCP) may establish the fistulous
      communication between the pancreas and pleural cavity. The optimal treatment
      strategy has traditionally been medical management with exocrine suppression with
      octreotide and ERCP stenting of the fistulous pancreatic duct. Operative therapy
      considered in the event patient fails to respond to conservative management.
      There is, however, a lack of clarity regarding the management, and the literature
      is reviewed here to assess the present view on its pathogenesis, investigations,
      and management.

PMID- 22454556
TI  - Inertial focusing dynamics in spiral microchannels.
AB  - This report details a comprehensive study of inertial focusing dynamics and
      particle behavior in low aspect ratio (h/w ~ 1/1 to 1/8) spiral microchannels. A
      continuum of particle streak behavior is shown with longitudinal, cross
      sectional, and velocity resolution, yielding a large analyzed parameter space.
      The dataset is then summarized and compared to prior results from both straight
      microchannels and other low aspect ratio spiral microchannel designs. Breakdown
      of focusing into a primary and secondary fluorescent streak is observed in the
      lowest aspect ratio channels at high average downstream velocities. Streak
      movement away from the theoretically predicted near inner wall equilibrium
      position towards the center of the channel at high average downstream velocities
      is also detailed as a precursor to breakdown. State diagrams detail the overall
      performance of each device including values of the required channel lengths and
      the range of velocities over which quality focusing can be achieved.

PMID- 22454557
TI  - Optimal control of gene mutation in DNA replication.
AB  - We propose a molecular-level control system view of the gene mutations in DNA
      replication from the finite field concept. By treating DNA sequences as state
      variables, chemical mutagens and radiation as control inputs, one cell cycle as a
      step increment, and the measurements of the resulting DNA sequence as outputs, we
      derive system equations for both deterministic and stochastic discrete-time,
      finite-state systems of different scales. Defining the cost function as a
      summation of the costs of applying mutagens and the off-trajectory penalty, we
      solve the deterministic and stochastic optimal control problems by dynamic
      programming algorithm. In addition, given that the system is completely
      controllable, we find that the global optimum of both base-to-base and codon-to
      codon deterministic mutations can always be achieved within a finite number of
      steps.

PMID- 22454558
TI  - CVD and obesity in transitional Syria: a perspective from the Middle East.
AB  - PURPOSE: Syria is caught in the middle of a disruptive nutritional transition.
      Its healthcare system is distracted by challenges and successes in other areas
      while neglecting to address the onslaught of Syria's cardiovascular disease (CVD)
      epidemic. Despite the official viewpoint touting improvement in health
      indicators, current trends jeopardize population health, and several surveys in
      the Syrian population signal the epidemic spreading far and wide. The goal is to
      counteract the indifference towards obesity as a threat to Syrian's health, as
      the country is slowly becoming a leader in CVD mortality globally. METHODS:
      PubMed, World Health Organization, and official government websites were searched
      for primary surveys in Syria related to CVD morbidity, mortality, and risk
      factors. Inclusion criteria ensured that results maximized relevance while
      producing comparable studies. Statistical analysis was applied to detect the most
      common risk factor and significant differences in risk factor prevalence and CVD
      rates. RESULTS: Obesity remained the prevailing CVD risk factor except in older
      Syrian men, where smoking and hypertension were more common. CVD mortality was
      more common in males due to coronary disease, while stroke dominated female
      mortality. The young workforce is especially impacted, with 50% of CVD mortality
      occurring before age 65 years and an 81% prevalence of obesity in women over 45
      years. CONCLUSION: Syria can overcome its slow response to the CVD epidemic and
      curb further deterioration by reducing obesity and, thus, inheritance and
      clustering of risk factors. This can be achieved via multilayered awareness and
      intensive parental and familial involvement. Extinguishing the CVD epidemic is
      readily achievable as demonstrated in other countries.

PMID- 22454559
TI  - Nebivolol: impact on cardiac and endothelial function and clinical utility.
AB  - Endothelial dysfunction is a systemic pathological state of the endothelium
      characterized by a reduction in the bioavailability of vasodilators, essentially
      nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as
      disarrangement in vascular wall metabolism and function. One of the key factors
      in endothelial dysfunction is overproduction of reactive oxygen species which
      participate in the development of hypertension, atherosclerosis, diabetes,
      cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke.
      Because impaired endothelial activity is believed to have a major causal role in
      the pathophysiology of vascular disease, hypertension, and heart failure,
      therapeutic agents which modify this condition are of clinical interest.
      Nebivolol is a third-generation beta-blocker with high selectivity for beta1
      adrenergic receptors and causes vasodilation by interaction with the endothelial
      L-arginine/ nitric oxide pathway. This dual mechanism of action underscores
      several hemodynamic qualities of nebivolol, which include reductions in heart
      rate and blood pressure and improvements in systolic and diastolic function.
      Although nebivolol reduces blood pressure to a degree similar to that of
      conventional beta-blockers and other types of antihypertensive drugs, it may have
      advantages in populations with difficult-to-treat hypertension, such as patients
      with heart failure along with other comorbidities, like diabetes and obesity, and
      elderly patients in whom nitric oxide-mediated endothelial dysfunction may be
      more pronounced. Furthermore, recent data indicate that nebivolol appears to be a
      cost-effective treatment for elderly patients with heart failure compared with
      standard care. Thus, nebivolol is an effective and well tolerated agent with
      benefits above those of traditional beta-blockers due to its influence on nitric
      oxide release, which give it singular hemodynamic effects, cardioprotective
      activity, and a good tolerability profile. This paper reviews the pharmacology
      structure and properties of nebivolol, focusing on endothelial dysfunction,
      clinical utility, comparative efficacy, side effects, and quality of life in
      general with respect to the other antihypertensive agents.

PMID- 22454560
TI  - Lower extremity venous thrombosis in patients younger than 50 years of age.
AB  - AIM: Lower extremity deep venous thrombosis in the young adult is uncommon and
      has not been well studied in the literature. The aim of this study is to define
      risk factors for deep venous thrombosis among patients younger than 50 years of
      age, to compare them with a control group, and to suggest recommendations for the
      management and treatment of venous thrombosis in this particular group of
      patients. METHODS: From January 2003 to January 2011, 66 consecutive Lebanese
      patients (29 males and 37 females) younger than 50 years, diagnosed in an
      academic tertiary-care center with lower extremity deep venous thrombosis by
      color flow duplex scan, were retrospectively reviewed. Their age varied between
      21 and 50 years (mean 38.7 years). The control group included 217 patients (86
      males and 131 females) older than 50 years (range: 50-96 years; mean 72.9 years).
      RESULTS: The most commonly reported risk factors in the younger age group were
      inherited thrombophilia (46.9% compared with 13.8% in the control group; P <
      0.001), pregnancy (18.2% compared with 0.5%; P < 0.001), treatment with estrogen
      drugs (13.6% compared with 2.3%; P = 0.001), and family history of venous
      thromboembolism (9.1% compared with 3.8%; P = 0.084). CONCLUSION: Inherited
      thrombophilia is the most commonly observed risk factor among patients younger
      than 50 years, with a prevalence of three times more than the control group.
      Young adults should be screened for thrombophilia even in the presence of
      transient acquired risk factors. Pregnancy and treatment with estrogen drugs
      essentially when associated with inherited thrombophilia represent a frequent
      cause of venous thrombosis among young female patients. Inferior vena cava
      abnormalities should be excluded in young patients with spontaneous proximal
      venous thrombosis especially when recurrent venous thrombosis or resistance to
      anticoagulation are observed.

PMID- 22454561
TI  - Major risk factors for the appearance of white-matter lesions on MRI in
      hypertensive patients with controlled blood pressure.
AB  - PURPOSE: Blood pressure (BP), age, and reduced renal function are major risk
      factors for white-matter lesions (WMLs) in the general population. However, it
      remains unclear whether or not the BP itself or other parameters related to the
      BP are associated with WMLs in hypertensive patients with well-controlled BP. We
      investigated the relationships of the presence of WMLs with the central systolic
      BP (cSBP) and estimated glomerular filtration rate (eGFR) in treated hypertensive
      patients. METHOD: We studied 185 hypertensive patients with median duration of
      hypertension, 10.0 years, whose BP is controlled to SBP and diastolic BP (DBP) of
      139 +/- 17 and 79 +/- 10 mmHg, respectively. We measured cSBP and brain magnetic
      resonance imaging (MRI) was examined within 2 weeks after last BP and biological
      measurements. RESULTS: Patients with higher-grade WMLs, as assessed by the
      presence of Scheltens deep white-matter hyperintensity (SDWMH) in the frontal
      (grade 0-2 vs 3-6) and parietal areas (grade 0-2 vs 3-6) where small arteries are
      affected at earlier stage of hypertension, as well as that of Fazekas deep white
      matter hyperintensity (FDWMH) (grade 2-3 vs 0-1) and Fazekas periventricular
      hyperintensity (FPVH) (grade 1-3 vs 0) were older, had higher serum creatinine
      levels, a longer duration of hypertension, and lower eGFR values. The grade of
      the WMLs was not associated with either the cSBP or the brachial SBP. In logistic
      regression analyses after adjustment for age, sex, cSBP, and hypertension
      duration, showed significant association between eGFR and WMLs. The patients with
      lower eGFR (<60 mL/minute/1.73 m(2)) tended to have higher grade WMLs. The odds
      ratio was 2.87 for FDWMH (P = 0.017), 1.99 for FPVH (P = 0.131), and 2.33 for
      SDWMH in the parietal area (P = 0.045). CONCLUSION: Presence of WMLs was
      associated with eGFR, but not with either the brachial SBP or cSBP in
      hypertensive patients with well-controlled BP.

PMID- 22454563
TI  - Performance of a protected wireless sensor network in a fire. Analysis of fire
      spread and data transmission.
AB  - The paper deals with a Wireless Sensor Network (WSN) as a reliable solution for
      capturing the kinematics of a fire front spreading over a fuel bed. To provide
      reliable information in fire studies and support fire fighting strategies, a
      Wireless Sensor Network must be able to perform three sequential actions: 1)
      sensing thermal data in the open as the gas temperature; 2) detecting a fire
      i.e., the spatial position of a flame; 3) tracking the fire spread during its
      spatial and temporal evolution. One of the great challenges in performing fire
      front tracking with a WSN is to avoid the destruction of motes by the fire. This
      paper therefore shows the performance of Wireless Sensor Network when the motes
      are protected with a thermal insulation dedicated to track a fire spreading
      across vegetative fuels on a field scale. The resulting experimental WSN is then
      used in series of wildfire experiments performed in the open in vegetation areas
      ranging in size from 50 to 1,000 m(2).

PMID- 22454562
TI  - Prognostic impacts of hypoxic markers in soft tissue sarcoma.
AB  - Background. We aimed to explore the prognostic impact of the hypoxia-induced
      factors (HIFalphas) 1 and 2, the metabolic HIF-regulated glucose transporter GLUT
      1, and carbonic anhydrase IX (CAIX) in non-gastrointestinal stromal tumor soft
      tissue sarcomas (non-GIST STS). Methods. Duplicate cores with viable tumor tissue
      from 206 patients with non-GIST STS were obtained and tissue microarrays were
      constructed. Immunohistochemistry (IHC) was used to evaluate expression of
      hypoxic markers. Results. In univariate analyses, GLUT-1 (P < 0.001) and HIF
      2alpha (P = 0.032) expression correlated significantly with a poor disease
      specific survival (DSS). In the multivariate analysis, however, only high
      expression of GLUT-1 (HR 1.7, CI 95% 1.1-2.7, P = 0.021) was a significant
      independent prognostic indicator of poor DSS. Conclusion. GLUT-1 is a significant
      independent negative prognostic factor in non-GIST STS.

PMID- 22454564
TI  - Inertial and magnetic sensor data compression considering the estimation error.
AB  - This paper presents a compression method for inertial and magnetic sensor data,
      where the compressed data are used to estimate some states. When sensor data are
      bounded, the proposed compression method guarantees that the compression error is
      smaller than a prescribed bound. The manner in which this error bound affects the
      bit rate and the estimation error is investigated. Through the simulation, it is
      shown that the estimation error is improved by 18.81% over a test set of 12 cases
      compared with a filter that does not use the compression error bound.

PMID- 22454565
TI  - A 1,000 Frames/s Programmable Vision Chip with Variable Resolution and Row-Pixel
      Mixed Parallel Image Processors.
AB  - A programmable vision chip with variable resolution and row-pixel-mixed parallel
      image processors is presented. The chip consists of a CMOS sensor array, with row
      parallel 6-bit Algorithmic ADCs, row-parallel gray-scale image processors, pixel
      parallel SIMD Processing Element (PE) array, and instruction controller. The
      resolution of the image in the chip is variable: high resolution for a focused
      area and low resolution for general view. It implements gray-scale and binary
      mathematical morphology algorithms in series to carry out low-level and mid-level
      image processing and sends out features of the image for various applications. It
      can perform image processing at over 1,000 frames/s (fps). A prototype chip with
      64 * 64 pixels resolution and 6-bit gray-scale image is fabricated in 0.18 MUm
      Standard CMOS process. The area size of chip is 1.5 mm * 3.5 mm. Each pixel size
      is 9.5 MUm * 9.5 MUm and each processing element size is 23 MUm * 29 MUm. The
      experiment results demonstrate that the chip can perform low-level and mid-level
      image processing and it can be applied in the real-time vision applications, such
      as high speed target tracking.

PMID- 22454566
TI  - Oscillation control algorithms for resonant sensors with applications to
      vibratory gyroscopes.
AB  - We present two oscillation control algorithms for resonant sensors such as
      vibratory gyroscopes. One control algorithm tracks the resonant frequency of the
      resonator and the other algorithm tunes it to the specified resonant frequency by
      altering the resonator dynamics. Both algorithms maintain the specified amplitude
      of oscillations. The stability of each of the control systems is analyzed using
      the averaging method, and quantitative guidelines are given for selecting the
      control gains needed to achieve stability. The effects of displacement
      measurement noise on the accuracy of tracking and estimation of the resonant
      frequency are also analyzed. The proposed control algorithms are applied to two
      important problems in a vibratory gyroscope. The first is the leading-following
      resonator problem in the drive axis of MEMS dual-mass vibratory gyroscope where
      there is no mechanical linkage between the two proof-masses and the second is the
      on-line modal frequency matching problem in a general vibratory gyroscope.
      Simulation results demonstrate that the proposed control algorithms are
      effective. They ensure the proof-masses to oscillate in an anti-phase manner with
      the same resonant frequency and oscillation amplitude in a dual-mass gyroscope,
      and two modal frequencies to match in a general vibratory gyroscope.

PMID- 22454567
TI  - S3: school zone safety system based on wireless sensor network.
AB  - School zones are areas near schools that have lower speed limits and where
      illegally parked vehicles pose a threat to school children by obstructing them
      from the view of drivers. However, these laws are regularly flouted. Thus, we
      propose a novel wireless sensor network application called School zone Safety
      System (S3) to help regulate the speed limit and to prevent illegal parking in
      school zones. S3 detects illegally parked vehicles, and warns the driver and
      records the license plate number. To reduce the traveling speed of vehicles in a
      school zone, S3 measures the speed of vehicles and displays the speed to the
      driver via an LED display, and also captures the image of the speeding vehicle
      with a speed camera. We developed a state machine based vehicle detection
      algorithm for S3. From extensive experiments in our testbeds and data from a real
      school zone, it is shown that the system can detect all kinds of vehicles, and
      has an accuracy of over 95% for speed measurement. We modeled the battery life
      time of a sensor node and validated the model with a downscaled measurement; we
      estimate the battery life time to be over 2 years. We have deployed S3 in 15
      school zones in 2007, and we have demonstrated the robustness of S3 by operating
      them for over 1 year.

PMID- 22454568
TI  - Intrusion-aware alert validation algorithm for cooperative distributed intrusion
      detection schemes of wireless sensor networks.
AB  - Existing anomaly and intrusion detection schemes of wireless sensor networks have
      mainly focused on the detection of intrusions. Once the intrusion is detected, an
      alerts or claims will be generated. However, any unidentified malicious nodes in
      the network could send faulty anomaly and intrusion claims about the legitimate
      nodes to the other nodes. Verifying the validity of such claims is a critical and
      challenging issue that is not considered in the existing cooperative-based
      distributed anomaly and intrusion detection schemes of wireless sensor networks.
      In this paper, we propose a validation algorithm that addresses this problem.
      This algorithm utilizes the concept of intrusion-aware reliability that helps to
      provide adequate reliability at a modest communication cost. In this paper, we
      also provide a security resiliency analysis of the proposed intrusion-aware alert
      validation algorithm.

PMID- 22454569
TI  - Orientation of airborne laser scanning point clouds with multi-view, multi-scale
      image blocks.
AB  - Comprehensive 3D modeling of our environment requires integration of terrestrial
      and airborne data, which is collected, preferably, using laser scanning and
      photogrammetric methods. However, integration of these multi-source data requires
      accurate relative orientations. In this article, two methods for solving relative
      orientation problems are presented. The first method includes registration by
      minimizing the distances between of an airborne laser point cloud and a 3D model.
      The 3D model was derived from photogrammetric measurements and terrestrial laser
      scanning points. The first method was used as a reference and for validation.
      Having completed registration in the object space, the relative orientation
      between images and laser point cloud is known. The second method utilizes an
      interactive orientation method between a multi-scale image block and a laser
      point cloud. The multi-scale image block includes both aerial and terrestrial
      images. Experiments with the multi-scale image block revealed that the accuracy
      of a relative orientation increased when more images were included in the block.
      The orientations of the first and second methods were compared. The comparison
      showed that correct rotations were the most difficult to detect accurately by
      using the interactive method. Because the interactive method forces laser
      scanning data to fit with the images, inaccurate rotations cause corresponding
      shifts to image positions. However, in a test case, in which the orientation
      differences included only shifts, the interactive method could solve the relative
      orientation of an aerial image and airborne laser scanning data repeatedly within
      a couple of centimeters.

PMID- 22454570
TI  - MCBT: Multi-Hop Cluster Based Stable Backbone Trees for Data Collection and
      Dissemination in WSNs.
AB  - We propose a stable backbone tree construction algorithm using multi-hop clusters
      for wireless sensor networks (WSNs). The hierarchical cluster structure has
      advantages in data fusion and aggregation. Energy consumption can be decreased by
      managing nodes with cluster heads. Backbone nodes, which are responsible for
      performing and managing multi-hop communication, can reduce the communication
      overhead such as control traffic and minimize the number of active nodes.
      Previous backbone construction algorithms, such as Hierarchical Cluster-based
      Data Dissemination (HCDD) and Multicluster, Mobile, Multimedia radio network
      (MMM), consume energy quickly. They are designed without regard to appropriate
      factors such as residual energy and degree (the number of connections or edges to
      other nodes) of a node for WSNs. Thus, the network is quickly disconnected or has
      to reconstruct a backbone. We propose a distributed algorithm to create a stable
      backbone by selecting the nodes with higher energy or degree as the cluster
      heads. This increases the overall network lifetime. Moreover, the proposed method
      balances energy consumption by distributing the traffic load among nodes around
      the cluster head. In the simulation, the proposed scheme outperforms previous
      clustering schemes in terms of the average and the standard deviation of residual
      energy or degree of backbone nodes, the average residual energy of backbone nodes
      after disseminating the sensed data, and the network lifetime.

PMID- 22454571
TI  - Deflection, frequency, and stress characteristics of rectangular, triangular, and
      step profile microcantilevers for biosensors.
AB  - This study presents the deflection, resonant frequency and stress results of
      rectangular, triangular, and step profile microcantilevers subject to surface
      stress. These cantilevers can be used as the sensing element in microcantilever
      biosensors. To increase the overall sensitivity of microcantilever biosensors,
      both the deflection and the resonant frequency of the cantilever should be
      increased. The effect of the cantilever profile change and the cantilever cross
      section shape change is first investigated separately and then together. A finite
      element code ANSYS Multiphysics is used and solid finite elements cantilever
      models are solved. A surface stress of 0.05 N/m was applied to the top surface of
      the cantilevers. The cantilevers are made of silicon with elastic modulus 130 GPa
      and Poisson's ratio 0.28. To show the conformity of this study, the numerical
      results are compared against their analytical ones. Results show that triangular
      and step cantilevers have better deflection and frequency characteristics than
      rectangular ones.

PMID- 22454572
TI  - Meat quality assessment by electronic nose (machine olfaction technology).
AB  - Over the last twenty years, newly developed chemical sensor systems (so called
      "electronic noses") have made odor analyses possible. These systems involve
      various types of electronic chemical gas sensors with partial specificity, as
      well as suitable statistical methods enabling the recognition of complex odors.
      As commercial instruments have become available, a substantial increase in
      research into the application of electronic noses in the evaluation of volatile
      compounds in food, cosmetic and other items of everyday life is observed. At
      present, the commercial gas sensor technologies comprise metal oxide
      semiconductors, metal oxide semiconductor field effect transistors, organic
      conducting polymers, and piezoelectric crystal sensors. Further sensors based on
      fibreoptic, electrochemical and bi-metal principles are still in the
      developmental stage. Statistical analysis techniques range from simple graphical
      evaluation to multivariate analysis such as artificial neural network and radial
      basis function. The introduction of electronic noses into the area of food is
      envisaged for quality control, process monitoring, freshness evaluation, shelf
      life investigation and authenticity assessment. Considerable work has already
      been carried out on meat, grains, coffee, mushrooms, cheese, sugar, fish, beer
      and other beverages, as well as on the odor quality evaluation of food packaging
      material. This paper describes the applications of these systems for meat quality
      assessment, where fast detection methods are essential for appropriate product
      management. The results suggest the possibility of using this new technology in
      meat handling.

PMID- 22454574
TI  - Building reconstruction by target based graph matching on incomplete laser data:
      analysis and limitations.
AB  - With the increasing point densities provided by airborne laser scanner (ALS) data
      the requirements on derived products also increase. One major application of ALS
      data is to provide input for 3D city models. Modeling of roof faces, (3D) road
      and terrain surfaces can partially be done in an automated manner, although many
      such approaches are still in a development stage. Problems in automatic building
      reconstruction lie in the dynamic area between assumptions and reality. Not every
      object in the data appears as the algorithm expects. Challenges are to detect
      areas that cannot be reconstructed automatically. This paper describes our
      contribution to the field of building reconstruction by proposing a target based
      graph matching approach that can handle both complete and incomplete laser data.
      Match results describe which target objects appear topologically in the data.
      Complete match results can be reconstructed in an automated manner. Quality
      parameters store information on how the model fits to the input data and which
      data has not been used. Areas where laser data only partly matches with target
      objects are detected automatically. Four datasets are analyzed in order to
      describe the quality of the automatically reconstructed roofs, and to point out
      the reasons why segments are left out from the automatic reconstruction. The
      reasons why these areas are left out include lack of data information and
      limitations of our initial target objects. Potential improvement to our approach
      is to include likelihood functions to the existence of topological relations.

PMID- 22454573
TI  - From lateral flow devices to a novel nano-color microfluidic assay.
AB  - Improving the performance of traditional diagnostic lateral flow assays combined
      with new manufacturing technologies is a primary goal in the research and
      development plans of diagnostic companies. Taking into consideration the
      components of lateral flow diagnostic test kits; innovation can include
      modification of labels, materials and device design. In recent years, Resonance
      Enhanced Absorption (REA) of metal nano-particles has shown excellent
      applicability in bio-sensing for the detection of a variety of bio-molecular
      binding interactions. In a novel approach, we have now integrated REA-assays in a
      diagnostic microfluidic setup thus resolving the bottleneck of long incubation
      times inherent in previously existing REA-assays and simultaneously integrated
      automated fabrication techniques for diagnostics manufacture. Due to the roller
      coating based technology and chemical resistance, we used PET-co-polyester as a
      substrate and a CO(2) laser ablation system as a fast, highly precise and
      contactless alternative to classical micro-milling. It was possible to detect
      biological binding within three minutes - visible to the eye as colored text
      readout within the REA-fluidic device. A two-minute in-situ silver enhancement
      was able to enhance the resonant color additionally, if required.

PMID- 22454575
TI  - Distortion of near-surface seawater temperature structure by a moored-buoy hull
      and its effect on skin temperature and heat flux estimates.
AB  - Previous studies have suggested that the accuracy of temperature measurements by
      surface-moored buoys may be affected by distortions of the near-surface
      temperature structure by the buoy hull on calm, sunny days. We obtained the first
      definite observational evidence that the temperature near the hull was not
      horizontally homogeneous at the same nominal depth. We observed large temperature
      differences of 1.0 K or more between thermometers at 0.2 m depth. The distortion
      of the surface temperature field yielded an error in estimates of daytime net
      surface heat flux up to more than 30 Wm(-2).

PMID- 22454576
TI  - Calibration of correlation radiometers using pseudo-random noise signals.
AB  - The calibration of correlation radiometers, and particularly aperture synthesis
      interferometric radiometers, is a critical issue to ensure their performance.
      Current calibration techniques are based on the measurement of the cross
      correlation of receivers' outputs when injecting noise from a common noise source
      requiring a very stable distribution network. For large interferometric
      radiometers this centralized noise injection approach is very complex from the
      point of view of mass, volume and phase/amplitude equalization. Distributed noise
      injection techniques have been proposed as a feasible alternative, but are unable
      to correct for the so-called "baseline errors" associated with the particular
      pair of receivers forming the baseline. In this work it is proposed the use of
      centralized Pseudo-Random Noise (PRN) signals to calibrate correlation
      radiometers. PRNs are sequences of symbols with a long repetition period that
      have a flat spectrum over a bandwidth which is determined by the symbol rate.
      Since their spectrum resembles that of thermal noise, they can be used to
      calibrate correlation radiometers. At the same time, since these sequences are
      deterministic, new calibration schemes can be envisaged, such as the correlation
      of each receiver's output with a baseband local replica of the PRN sequence, as
      well as new distribution schemes of calibration signals. This work analyzes the
      general requirements and performance of using PRN sequences for the calibration
      of microwave correlation radiometers, and particularizes the study to a potential
      implementation in a large aperture synthesis radiometer using an optical
      distribution network.

PMID- 22454577
TI  - An efficient and self-adapting localization in static wireless sensor networks.
AB  - Localization is one of the most important subjects in Wireless Sensor Networks
      (WSNs). To reduce the number of beacons and adopt probabilistic methods, some
      particle filter-based mobile beacon-assisted localization approaches have been
      proposed, such as Mobile Beacon-assisted Localization (MBL), Adapting MBL (A
      MBL), and the method proposed by Hang et al. Some new significant problems arise
      in these approaches, however. The first question is which probability
      distribution should be selected as the dynamic model in the prediction stage. The
      second is whether the unknown node adopts neighbors' observation in the update
      stage. The third is how to find a self-adapting mechanism to achieve more
      flexibility in the adapting stage. In this paper, we give the theoretical
      analysis and experimental evaluations to suggest which probability distribution
      in the dynamic model should be adopted to improve the efficiency in the
      prediction stage. We also give the condition for whether the unknown node should
      use the observations from its neighbors to improve the accuracy. Finally, we
      propose a Self-Adapting Mobile Beacon-assisted Localization (SA-MBL) approach to
      achieve more flexibility and achieve almost the same performance with A-MBL.

PMID- 22454578
TI  - Monitoring system for farming operations with wearable devices utilized sensor
      networks.
AB  - In order to automatically monitor farmers' activities, we propose a farm
      operation monitoring system using "Field Servers" and a wearable device equipped
      with an RFID reader and motion sensors. Our proposed system helps in recognizing
      farming operations by analyzing the data from the sensors and detected RFID tags
      that are attached to various objects such as farming materials, facilities, and
      machinery. This method can be applied to various situations without changing the
      conventional system. Moreover, this system provides useful information in real
      time and controls specific machines in a coordinated manner on the basis of
      recognized operation.

PMID- 22454579
TI  - Amperometric hydrogen peroxide biosensor based on immobilization of hemoglobin on
      a glassy carbon electrode modified with fe(3)o(4)/chitosan core-shell
      microspheres.
AB  - Novel magnetic Fe(3)O(4)/chitosan (CS) microspheres were prepared using magnetic
      Fe(3)O(4) nanoparticles and the natural macromolecule chitosan. Then, using an
      easy and effective hemoglobin (Hb) immobilization method, an innovative biosensor
      with a Fe(3)O(4)/CS-Hb-Fe(3)O(4)/CS "sandwich" configuration was constructed.
      This biosensor had a fast (less than 10 s) response to H(2)O(2) and excellent
      linear relationships were obtained in the concentration range of 5.0 * 10(-5) to
      1.8 * 10(-3) M and 1.8 * 10(-3) to 6.8 * 10(-3) M with a detection limit of 4.0 *
      10(-6) M (s/n = 3) under the optimum conditions. The apparent Michaelis-Menten
      constant K(m) was 0.29 mM and it showed the excellent biological activity of the
      fixed Hb. Moreover, the biosensor had long-time stability and good
      reproducibility. The method was used to determine H(2)O(2) concentration in real
      samples.

PMID- 22454580
TI  - Fabrication and Performance of MEMS-Based Pressure Sensor Packages Using
      Patterned Ultra-Thick Photoresists.
AB  - A novel plastic packaging of a piezoresistive pressure sensor using a patterned
      ultra-thick photoresist is experimentally and theoretically investigated. Two
      pressure sensor packages of the sacrifice-replacement and dam-ring type were used
      in this study. The characteristics of the packaged pressure sensors were
      investigated by using a finite-element (FE) model and experimental measurements.
      The results show that the thermal signal drift of the packaged pressure sensor
      with a small sensing-channel opening or with a thin silicon membrane for the dam
      ring approach had a high packaging induced thermal stress, leading to a high
      temperature coefficient of span (TCO) response of -0.19% span/ degrees C. The
      results also show that the thermal signal drift of the packaged pressure sensors
      with a large sensing-channel opening for sacrifice-replacement approach
      significantly reduced packaging induced thermal stress, and hence a low TCO
      response of -0.065% span/ degrees C. However, the packaged pressure sensors of
      both the sacrifice-replacement and dam-ring type still met the specification 
      0.2% span/ degrees C of the unpackaged pressure sensor. In addition, the size of
      proposed packages was 4 * 4 * 1.5 mm(3) which was about seven times less than the
      commercialized packages. With the same packaging requirement, the proposed
      packaging approaches may provide an adequate solution for use in other open
      cavity sensors, such as gas sensors, image sensors, and humidity sensors.

PMID- 22454581
TI  - Manufacture of Micromirror Arrays Using a CMOS-MEMS Technique.
AB  - In this study we used the commercial 0.35 MUm CMOS (complementary metal oxide
      semiconductor) process and simple maskless post-processing to fabricate an array
      of micromirrors exhibiting high natural frequency. The micromirrors were
      manufactured from aluminum; the sacrificial layer was silicon dioxide. Because we
      fabricated the micromirror arrays using the standard CMOS process, they have the
      potential to be integrated with circuitry on a chip. For post-processing we used
      an etchant to remove the sacrificial layer and thereby suspend the micromirrors.
      The micromirror array contained a circular membrane and four fixed beams set
      symmetrically around and below the circular mirror; these four fan-shaped
      electrodes controlled the tilting of the micromirror. A MEMS
      (microelectromechanical system) motion analysis system and a confocal 3D-surface
      topography were used to characterize the properties and configuration of the
      micromirror array. Each micromirror could be rotated in four independent
      directions. Experimentally, we found that the micromirror had a tilting angle of
      about 2.55 degrees  when applying a driving voltage of 40 V. The natural
      frequency of the micromirrors was 59.1 kHz.

PMID- 22454582
TI  - Mid-infrared sensing of organic pollutants in aqueous environments.
AB  - The development of chemical sensors for monitoring the levels of organic
      pollutants in the aquatic environment has received a great deal of attention in
      recent decades. In particular, the mid-infrared (MIR) sensor based on attenuated
      total reflectance (ATR) is a promising analytical tool that has been used to
      detect a variety of hydrocarbon compounds (i.e., aromatics, alkyl halides,
      phenols, etc.) dissolved in water. It has been shown that under certain
      conditions the MIR-ATR sensor is capable of achieving detection limits in the 10
      100 ppb concentration range. Since the infrared spectral features of every single
      organic molecule are unique, the sensor is highly selective, making it possible
      to distinguish between many different analytes simultaneously. This review paper
      discusses some of the parameters (i.e., membrane type, film thickness,
      conditioning) that dictate MIR-ATR sensor response. The performance of various
      chemoselective membranes which are used in the fabrication of the sensor will be
      evaluated. Some of the challenges associated with long-term environmental
      monitoring are also discussed.

PMID- 22454583
TI  - Determination of Glucose Concentration in Aqueous Solution Using ATR-WT-IR
      Technique.
AB  - Fourier transformation infrared (FT-IR) spectroscopy has been used to measure
      glucose concentrations in different matrices. The accuracy of the FT-IR technique
      does not meet the requirements of medical applications, so we have developed a
      new, efficient and precise method based on attenuated total reflectance coupled
      with wavelet transformation (ATR-WT-IR). One thousand interferograms, divided
      into training- and testing-sets, have been recorded from four glucose
      concentrations using an ATR-IR unit. Signals were subjected to (WT) and neural
      network (NN) study in order to design correlation algorithm. The Pearson's
      Correlation Coefficient (PCC) obtained by judging the predicted- against the real
      concentrations was 0.9954, with a mean square error of 8.4e-005. The proposed ATR
      WT-IR method shows efficiency in glucose prediction and could possibly to be
      integrated into a non-invasive monitoring technique.

PMID- 22454584
TI  - Gas Sensor Based on Photonic Crystal Fibres in the 2nu(3) and nu(2) + 2nu(3)
      Vibrational Bands of Methane.
AB  - In this work, methane detection is performed on the 2nu(3) and nu(2) + 2nu(3)
      absorption bands in the Near-Infrared (NIR) wavelength region using an all-fibre
      optical sensor. Hollow-core photonic bandgap fibres (HC-PBFs) are employed as gas
      cells due to their compactness, good integrability in optical systems and
      feasibility of long interaction lengths with gases. Sensing in the 2nu(3) band of
      methane is demonstrated to achieve a detection limit one order of magnitude
      better than that of the nu(2) + 2nu(3) band. Finally, the filling time of a HC
      PBF is demonstrated to be dependent on the fibre length and geometry.

PMID- 22454585
TI  - Design and implementation of a secure wireless mote-based medical sensor network.
AB  - A medical sensor network can wirelessly monitor vital signs of humans, making it
      useful for long-term health care without sacrificing patient comfort and
      mobility. For such a network to be viable, its design must protect data privacy
      and authenticity given that medical data are highly sensitive. We identify the
      unique security challenges of such a sensor network and propose a set of resource
      efficient mechanisms to address these challenges. Our solution includes (1) a
      novel two-tier scheme for verifying the authenticity of patient data, (2) a
      secure key agreement protocol to set up shared keys between sensor nodes and base
      stations, and (3) symmetric encryption/decryption for protecting data
      confidentiality and integrity. We have implemented the proposed mechanisms on a
      wireless mote platform, and our results confirm their feasibility.

PMID- 22454586
TI  - Bacteriophage t4 nanoparticles as materials in sensor applications: variables
      that influence their organization and assembly on surfaces.
AB  - Bacteriophage T4 nanoparticles possess characteristics that make them ideal
      candidates as materials for sensors, particularly as sensor probes. Their surface
      can be modified, either through genetic engineering or direct chemical
      conjugation to display functional moieties such as antibodies or other proteins
      to recognize a specific target. However, in order for T4 nanoparticles to be
      utilized as a sensor probe, it is necessary to understand and control the
      variables that determine their assembly and organization on a surface. The aim of
      this work is to discuss some of variables that we have identified as influencing
      the behavior of T4 nanoparticles on surfaces. The effect of pH, ionic strength,
      substrate characteristics, nanoparticle concentration and charge was addressed
      qualitatively using atomic force microscopy (AFM).

PMID- 22454587
TI  - A Comparison of RBF Neural Network Training Algorithms for Inertial Sensor Based
      Terrain Classification.
AB  - This paper introduces a comparison of training algorithms of radial basis
      function (RBF) neural networks for classification purposes. RBF networks provide
      effective solutions in many science and engineering fields. They are especially
      popular in the pattern classification and signal processing areas. Several
      algorithms have been proposed for training RBF networks. The Artificial Bee
      Colony (ABC) algorithm is a new, very simple and robust population based
      optimization algorithm that is inspired by the intelligent behavior of honey bee
      swarms. The training performance of the ABC algorithm is compared with the
      Genetic algorithm, Kalman filtering algorithm and gradient descent algorithm. In
      the experiments, not only well known classification problems from the UCI
      repository such as the Iris, Wine and Glass datasets have been used, but also an
      experimental setup is designed and inertial sensor based terrain classification
      for autonomous ground vehicles was also achieved. Experimental results show that
      the use of the ABC algorithm results in better learning than those of others.

PMID- 22454588
TI  - Spatio-Temporal Human Grip Force Analysis via Sensor Arrays.
AB  - This study describes a technique for measuring human grip forces exerted on a
      cylindrical object via a sensor array. Standardised resistor-based pressure
      sensor arrays for industrial and medical applications have been available for
      some time. We used a special 20 mm diameter grip rod that subjects could either
      move actively with their fingers in the horizontal direction or exert reactive
      forces against opposing forces generated in the rod by a linear motor. The sensor
      array film was attached to the rod by adhesive tape and covered approximately 45
      cm(2) of the rod surface. The sensor density was 4/cm(2) with each sensor having
      a force resolution of 0.1 N. A scan across all sensors resulted in a
      corresponding frame containing force values at a frame repetition rate of 150/s.
      The force value of a given sensor was interpreted as a pixel value resulting in a
      false-colour image. Based on remote sensed image analysis an algorithm was
      developed to distinguish significant force-representing pixels from those
      affected by noise. This allowed tracking of the position of identified fingers in
      subsequent frames such that spatio-temporal grip force profiles for individual
      fingers could be derived. Moreover, the algorithm allowed simultaneous
      measurement of forces exerted without any constraints on the number of fingers or
      on the position of the fingers. The system is thus well suited for basic and
      clinical research in human physiology as well as for studies in psychophysics.

PMID- 22454590
TI  - Piezoelectric and magnetoelectric thick films for fabricating power sources in
      wireless sensor nodes.
AB  - In this manuscript, we review the progress made in the synthesis of thick film
      based piezoelectric and magnetoelectric structures for harvesting energy from
      mechanical vibrations and magnetic field. Piezoelectric compositions in the
      system Pb(Zr,Ti)O(3)-Pb(Zn(1/3)Nb(2/3))O(3) (PZNT) have shown promise for
      providing enhanced efficiency due to higher energy density and thus form the base
      of transducers designed for capturing the mechanical energy. Laminate structures
      of PZNT with magnetostrictive ferrite materials provide large magnitudes of
      magnetoelectric coupling and are being targeted to capture the stray magnetic
      field energy. We analyze the models used to predict the performance of the energy
      harvesters and present a full system description.

PMID- 22454591
TI  - High-Resolution Images with Minimum Energy Dissipation and Maximum Field-of-View
      in Camera-Based Wireless Multimedia Sensor Networks.
AB  - High-resolution images with wide field of view are important in realizing many
      applications of wireless multimedia sensor networks. Previous works that
      generally use multi-tier topology and provide such images by increasing the
      capabilities of camera sensor nodes lead to an increase in network cost. On the
      other hand, the resulting energy consumption is a considerable issue that has not
      been seriously considered in previous works. In this paper, high-resolution
      images with wide field of view are generated without increasing the total cost of
      network and with minimum energy dissipation. This is achieved by using image
      stitching in WMSNs, designing a two-tier network topology with new structure, and
      proposing a camera selection algorithm. In the proposed two-tier structure, low
      cost camera sensor nodes are used only in the lower-tier and sensor nodes without
      camera are considered in the upper-tier which decreases total network cost as
      much as possible. Also, since a simplified image stitching method is implemented
      and a new algorithm for selecting active nodes is utilized, energy dissipation in
      the network is decreased by applying the proposed methods. The results of
      simulations supported the preceding statements.

PMID- 22454589
TI  - Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as
      Carriers of DNA and RNA.
AB  - We have evaluated the potential use of various polyamidoamine (PAMAM) dendrimer
      [dendrimer, generation (G) 2-4] conjugates with cyclodextrins (CyDs) as novel DNA
      and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer
      (G3) conjugate with alpha-CyD having an average degree of substitution (DS) of
      2.4 [alpha-CDE (G3, DS2)] displayed remarkable properties as DNA, shRNA and siRNA
      delivery carriers through the sensor function of alpha-CDEs toward nucleic acid
      drugs, cell surface and endosomal membranes. In an attempt to develop cell
      specific gene transfer carriers, we prepared sugar-appended alpha-CDEs. Of the
      various sugar-appended alpha-CDEs prepared, galactose- or mannose-appended alpha
      CDEs provided superior gene transfer activity to alpha-CDE in various cells, but
      not cell-specific gene delivery ability. However, lactose-appended alpha-CDE [Lac
      alpha-CDE (G2)] was found to possess asialoglycoprotein receptor (AgpR)-mediated
      hepatocyte-selective gene transfer activity, both in vitro and in vivo. Most
      recently, we prepared folate-poly(ethylene glycol)-appended alpha-CDE [Fol
      PalphaC (G3)] and revealed that Fol-PalphaC (G3) imparted folate receptor (FR)
      mediated cancer cell-selective gene transfer activity. Consequently, alpha-CDEs
      bearing integrated, multifunctional molecules may possess the potential to be
      novel carriers for DNA, shRNA and siRNA.

PMID- 22454592
TI  - Design of a water environment monitoring system based on wireless sensor
      networks.
AB  - A water environmental monitoring system based on a wireless sensor network is
      proposed. It consists of three parts: data monitoring nodes, data base station
      and remote monitoring center. This system is suitable for the complex and large
      scale water environment monitoring, such as for reservoirs, lakes, rivers,
      swamps, and shallow or deep groundwaters. This paper is devoted to the
      explanation and illustration for our new water environment monitoring system
      design. The system had successfully accomplished the online auto-monitoring of
      the water temperature and pH value environment of an artificial lake. The
      system's measurement capacity ranges from 0 to 80  degrees C for water
      temperature, with an accuracy of +/-0.5  degrees C; from 0 to 14 on pH value,
      with an accuracy of +/-0.05 pH units. Sensors applicable to different water
      quality scenarios should be installed at the nodes to meet the monitoring demands
      for a variety of water environments and to obtain different parameters. The
      monitoring system thus promises broad applicability prospects.

PMID- 22454593
TI  - Preparation of a polypyrrole-polyvinylsulphonate composite film biosensor for
      determination of cholesterol based on entrapment of cholesterol oxidase.
AB  - In this paper, a novel amperometric cholesterol biosensor with immobilization of
      cholesterol oxidase on electrochemically polymerized polypyrrole
      polyvinylsulphonate (PPy-PVS) films has been accomplished via the entrapment
      technique on the surface of a platinum electrode. Electropolymerization of
      pyrrole and polyvinylsulphonate on the Pt surface was carried out by cyclic
      voltammetry between -1.0 and +2.0 V (vs. Ag/AgCl) at a scan rate of 100 mV upon
      the Pt electrode with an electrochemical cell containing pyrrole and
      polyvinylsulphonate. The amperometric determination is based on the
      electrochemical detection of H(2)O(2) generated in the enzymatic reaction of
      cholesterol. Determination of cholesterol was carried out by the oxidation of
      enzymatically produced H(2)O(2) at 0.4 V vs. Ag/AgCl. The effects of pH and
      temperature were investigated and optimum parameters were found to be 7.25 and 35
      degrees C, respectively. The storage stability and operational stability of the
      enzyme electrode were also studied. The results show that 32% of the response
      current was retained after 19 activity assays. The prepared cholesterol biosensor
      retained 43% of initial activity after 45 days when stored in 0.1 M phosphate
      buffer solution at 4  degrees C.

PMID- 22454594
TI  - A self-referencing intensity based polymer optical fiber sensor for liquid
      detection.
AB  - A novel self-referencing fiber optic intensity sensor based on bending losses of
      a partially polished polymer optical fiber (POF) coupler is presented. The
      coupling ratio (K) depends on the external liquid in which the sensor is
      immersed. It is possible to distinguish between different liquids and to detect
      their presence. Experimental results for the most usual liquids found in
      industry, like water and oil, are given. K value increases up to 10% from the
      nominal value depending on the liquid. Sensor temperature dependence has also
      been studied for a range from 25  degrees C (environmental condition) to 50 
      degrees C. Any sector requiring liquid level measurements in flammable
      atmospheres can benefit from this intrinsically safe technology.

PMID- 22454595
TI  - A novel design of grooved fibers for fiber-optic localized plasmon resonance
      biosensors.
AB  - Bio-molecular recognition is detected by the unique optical properties of self
      assembled gold nanoparticles on the unclad portions of an optical fiber whose
      surfaces have been modified with a receptor. To enhance the performance of the
      sensing platform, the sensing element is integrated with a microfluidic chip to
      reduce sample and reagent volume, to shorten response time and analysis time, as
      well as to increase sensitivity. The main purpose of the present study is to
      design grooves on the optical fiber for the FO-LPR microfluidic chip and
      investigate the effect of the groove geometry on the biochemical binding kinetics
      through simulations. The optical fiber is designed and termed as U-type or D-type
      based on the shape of the grooves. The numerical results indicate that the design
      of the D-type fiber exhibits efficient performance on biochemical binding. The
      grooves designed on the optical fiber also induce chaotic advection to enhance
      the mixing in the microchannel. The mixing patterns indicate that D-type grooves
      enhance the mixing more effectively than U-type grooves. D-type fiber with six
      grooves is the optimum design according to the numerical results. The
      experimental results show that the D-type fiber could sustain larger elongation
      than the U-type fiber. Furthermore, this study successfully demonstrates the
      feasibility of fabricating the grooved optical fibers by the femtosecond laser,
      and making a transmission-based FO-LPR probe for chemical sensing. The sensor
      resolution of the sensor implementing the D-type fiber modified by gold
      nanoparticles was 4.1 * 10(-7) RIU, which is much more sensitive than that of U
      type optical fiber (1.8 * 10(-3) RIU).

PMID- 22454597
TI  - A comprehensive review of one-dimensional metal-oxide nanostructure
      photodetectors.
AB  - One-dimensional (1D) metal-oxide nanostructures are ideal systems for exploring a
      large number of novel phenomena at the nanoscale and investigating size and
      dimensionality dependence of nanostructure properties for potential applications.
      The construction and integration of photodetectors or optical switches based on
      such nanostructures with tailored geometries have rapidly advanced in recent
      years. Active 1D nanostructure photodetector elements can be configured either as
      resistors whose conductions are altered by a charge-transfer process or as field
      effect transistors (FET) whose properties can be controlled by applying
      appropriate potentials onto the gates. Functionalizing the structure surfaces
      offers another avenue for expanding the sensor capabilities. This article
      provides a comprehensive review on the state-of-the-art research activities in
      the photodetector field. It mainly focuses on the metal oxide 1D nanostructures
      such as ZnO, SnO(2), Cu(2)O, Ga(2)O(3), Fe(2)O(3), In(2)O(3), CdO, CeO(2), and
      their photoresponses. The review begins with a survey of quasi 1D metal-oxide
      semiconductor nanostructures and the photodetector principle, then shows the
      recent progresses on several kinds of important metal-oxide nanostructures and
      their photoresponses and briefly presents some additional prospective metal-oxide
      1D nanomaterials. Finally, the review is concluded with some perspectives and
      outlook on the future developments in this area.

PMID- 22454598
TI  - A Unified Multi-Functional Dynamic Spectrum Access Framework: Tutorial, Theory
      and Multi-GHz Wideband Testbed.
AB  - Dynamic spectrum access is a must-have ingredient for future sensors that are
      ideally cognitive. The goal of this paper is a tutorial treatment of wideband
      cognitive radio and radar-a convergence of (1) algorithms survey, (2) hardware
      platforms survey, (3) challenges for multi-function (radar/communications) multi
      GHz front end, (4) compressed sensing for multi-GHz waveforms-revolutionary A/D,
      (5) machine learning for cognitive radio/radar, (6) quickest detection, and (7)
      overlay/underlay cognitive radio waveforms. One focus of this paper is to address
      the multi-GHz front end, which is the challenge for the next-generation cognitive
      sensors. The unifying theme of this paper is to spell out the convergence for
      cognitive radio, radar, and anti-jamming. Moore's law drives the system functions
      into digital parts. From a system viewpoint, this paper gives the first
      comprehensive treatment for the functions and the challenges of this multi
      function (wideband) system. This paper brings together the inter-disciplinary
      knowledge.

PMID- 22454596
TI  - Exploiting Surface Plasmon Resonance (SPR) Technology for the Identification of
      Fibroblast Growth Factor-2 (FGF2) Antagonists Endowed with Antiangiogenic
      Activity.
AB  - Angiogenesis, the process of new blood vessel formation, is implicated in various
      physiological/pathological conditions, including embryonic development,
      inflammation and tumor growth. Fibroblast growth factor-2 (FGF2) is a heparin
      binding angiogenic growth factor involved in various physiopathological
      processes, including tumor neovascularization. Accordingly, FGF2 is considered a
      target for antiangiogenic therapies. Thus, numerous natural/synthetic compounds
      have been tested for their capacity to bind and sequester FGF2 in the
      extracellular environment preventing its interaction with cellular receptors. We
      have exploited surface plasmon resonance (SPR) technique in search for
      antiangiogenic FGF2 binders/antagonists. In this review we will summarize our
      experience in SPR-based angiogenesis research, with the aim to validate SPR as a
      first line screening for the identification of antiangiogenic compounds.

PMID- 22454599
TI  - Evolution and conservation of predicted inclusion membrane proteins in
      chlamydiae.
AB  - Chlamydia spp. are obligate intracellular pathogens that replicate within a
      vacuole termed the inclusion. Chlamydiae extensively modify the inclusion
      membrane via the insertion of chlamydial inclusion membrane proteins (Incs) which
      decorate the cytosolic face of the inclusion. We have assessed the overall
      relatedness and phylogeny of Incs in order to identify potential evolutionary
      trends. Despite a high degree of conservation among Incs within C. trachomatis
      serovars, phylogenetic analysis showed that some Incs cluster according to
      clinical groupings suggesting that certain Incs may contribute to tissue tropism.
      Bioinformatic predictions identified Incs in five chlamydial species: 55 in C.
      trachomatis, 68 in C. felis, 92 in C. pneumoniae, 79 in C. caviae, and 54 in C.
      muridarum. Inc homologues were compared between chlamydial species and 23 core
      Incs were identified as shared among all species. Genomic expansion of Incs was
      identified in C. pneumoniae, C. caviae, and C. felis but not C. trachomatis or C.
      muridarum.

PMID- 22454600
TI  - Sequential organ failure assessment score for evaluating organ failure and
      outcome of severe maternal morbidity in obstetric intensive care.
AB  - OBJECTIVE: To evaluate the performance of Sequential Organ Failure Assessment
      (SOFA) score in cases of severe maternal morbidity (SMM). DESIGN: Retrospective
      study of diagnostic validation. Setting. An obstetric intensive care unit (ICU)
      in Brazil. Population. 673 women with SMM. MAIN OUTCOME MEASURES: mortality and
      SOFA score. Methods. Organ failure was evaluated according to maximum score for
      each one of its six components. The total maximum SOFA score was calculated using
      the poorest result of each component, reflecting the maximum degree of alteration
      in systemic organ function. RESULTS: highest total maximum SOFA score was
      associated with mortality, 12.06 +/- 5.47 for women who died and 1.87 +/- 2.56
      for survivors. There was also a significant correlation between the number of
      failing organs and maternal mortality, ranging from 0.2% (no failure) to 85.7%
      (>=3 organs). Analysis of the area under the receiver operating characteristic
      (ROC) curve (AUC) confirmed the excellent performance of total maximum SOFA score
      for cases of SMM (AUC = 0.958). CONCLUSIONS: Total maximum SOFA score proved to
      be an effective tool for evaluating severity and estimating prognosis in cases of
      SMM. Maximum SOFA score may be used to conceptually define and stratify the
      degree of severity in cases of SMM.

PMID- 22454601
TI  - A population survey in Italy based on the ICF classification: recognizing persons
      with severe disability.
AB  - Aim of this paper is to describe functioning of subjects with "severe disability"
      collected with a protocol based on the International Classification of
      Functioning, Disability, and Health. It included sections on body functions and
      structures (BF and BS), activities and participation (A&P), and environmental
      factors (EF). In A&P, performance without personal support (WPS) was added to
      standard capacity and performance. Persons with severe disability were those
      reporting a number of very severe/complete problems in BF or in A&P-capacity
      superior to mean + 1SD. Correlations between BF and A&P and differences between
      capacity, performance-WPS, and performance were assessed with Spearman's
      coefficient. Out of 1051, 200 subjects were considered as severely disabled. Mild
      to moderate correlations between BF and A&P were reported (between 0.148 and
      0.394 when the full range of impairments/limitations was taken into account;
      between 0.198 and 0.285 when only the severe impairments/limitations were taken
      into account); performance-WPS was less similar to performance than to capacity.
      Our approach enabled identifying subjects with "severe disability" and separating
      the effect of personal support from that of devices, policies, and service
      provision.

PMID- 22454602
TI  - Clinical manifestations vary with different age spectrums in infants with
      Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis with unknown
      etiology. The diagnosis of KD depends on clinical manifestations. The prevalence
      of coronary artery abnormality (CAA) is 11.0% and results in cardiac sequelae,
      such as myocardial infarction or coronary aneurysm, which are the most serious
      complications in KD. METHODS: We divided KD's children into different age groups:
      <=6 months old, 7 months to 1 year old, and >1 year old, respectively. Different
      parameters were compared in each group. RESULTS: Infants <=6 months old are less
      likely to fulfill KD's major diagnostic criteria within 10 days, are prone to
      develop incomplete KD with the lowest cholesterol level, and have the greatest
      chance to have CAA and the laboratory features associated with CAA, such as the
      longest time needed to confirm CA diagnosis, lower hemoglobin level, lower
      albumin level, and higher platelet count. Infants <1 year old develop higher
      percentage of leukocytosis and sterile pyuria. But this group has fewer patients
      with neck lymphadenopathy.

PMID- 22454604
TI  - Signal persistence of bispectral index and state entropy during surgical
      procedure under sedation.
AB  - INTRODUCTION: Bispectral index (BIS) and state entropy (SE) are prone to
      artifacts, especially due to electrocautery (EC). We compared the incidence of
      artifacts in BIS and SE during surgery under local anesthesia and sedation.
      METHODS: 28 females undergoing breast surgery under local anesthesia and sedation
      were studied. Simultaneous BIS and SE measurements were recorded every 10
      seconds. Artifact was defined as a failure of the device to display a numerical
      value while the electrodes remained appropriately attached to the patient's
      forehead. Ratio of artifact to good signal was compared between BIS and SE in the
      presence or absence of EC use. RESULTS: 7679 data points were collected from 28
      patients. Overall, artifact incidence was similar in BIS and SE (6.2% and 6.3%,
      resp.). In the presence of EC (1370 data points), BIS had significantly more
      artifact compared to SE (18.6% versus 6.4%, P < 0.0001). Without EC (6309 data
      points), BIS had significantly less artifact compared to SE (4.1% versus 7.3%, P
      < 0.0001). DISCUSSION: BIS and SE were comparable for incidence of artifacts in
      patients under sedation. Use of EC lead to more artifact in BIS than SE.
      Conversely, BIS had fewer artifacts than SE when there was no EC use.

PMID- 22454603
TI  - Children in vegetative state and minimally conscious state: patients' condition
      and caregivers' burden.
AB  - Caring for children in vegetative state (VS) or minimally conscious state (MCS)
      challenges parents and impacts on their well-being. This study aims to evaluate
      caregivers' health condition, coping, anxiety and depression levels, and how
      these issues relate to children's disability. 35 children with VS and MCS were
      administered the disability rating scale (DRS) and 35 caregivers completed the
      Coping Orientations to Problem Experiences, Short Form-12, Beck Depression
      Inventory, and the Spielberger State-Trait Anxiety Inventory-Y. Children were
      mainly males (68.6%), hosted at domicile (77.1%), and diagnosed with VS (60%),
      with anoxic aetiology (45.7%). Caregivers were mainly mothers (85.7%), married
      (82.9%), and housewives (51.4%); 60% declared financial difficulties, and 82.9%
      provided full-time assistance. 57.2% reported depressive symptoms, poor mental
      health, and high level of state and trait anxiety. "Problem-oriented" (P < 0.001)
      and "emotional-oriented" (P < 0.001), were more adopted than "potentially
      dysfunctional" ones. DRS scores (mean = 22.0; SD = 1.9) did not significantly
      correlate to any psychological measure. Rehabilitative programs for children with
      SV and SMC should also provide interventions on surrounding systems: improving
      the network of psychological support and social assistance may decrease the
      burden of caregivers and, in turn, improve caring abilities and children quality
      of life.

PMID- 22454605
TI  - BNP and admission glucose as in-hospital mortality predictors in non-ST elevation
      myocardial infarction.
AB  - OBJECTIVES: Admission hyperglycemia and B-type natriuretic peptide (BNP) are
      associated with mortality in acute coronary syndromes, but no study compares
      their prediction in-hospital death. METHODS: Patients with non-ST-elevation
      myocardial infarction (NSTEMI), in-hospital mortality and two-year mortality or
      readmission were compared for area under the curve (AUC), sensitivity (SEN),
      specificity (SPE), positive predictive value (PPV), negative predictive value
      (NPV), and accuracy (ACC) of glycemia and BNP. RESULTS: Respectively, AUC, SEN,
      SPE, PPV, NPV, and ACC for prediction of in-hospital mortality were 0.815, 71.4%,
      84.3%, 26.3%, 97.4%, and 83.3% for glycemia = 200 mg/dL and 0.748, 71.4%, 68.5%,
      15.2%, 96.8% and 68.7% for BNP = 300 pg/mL. AUC of glycemia was similar to BNP (P
      = 0.411). In multivariate analysis we found glycemia >=200mg/dL related to in
      hospital death (P = 0.004). No difference was found in two-year mortality or
      readmission in BNP or hyperglycemic subgroups. CONCLUSION: Hyperglycemia was an
      independent risk factor for in-hospital mortality in NSTEMI and had a good ROC
      curve level. Hyperglycemia and BNP, although poor in-hospital predictors of
      unfavorable events, were independent risk factors for death or length of stay >10
      days. No relation was found between hyperglycemia or BNP and long-term events.

PMID- 22454606
TI  - The presence of visual neglect after thrombolytic treatment in patients with
      right hemisphere stroke.
AB  - Visual neglect (VN) is a common consequence of right hemisphere (RH) stroke. The
      aims of this study were to explore the presence of VN after RH stroke in the
      patients with (T+) or without (T-) thrombolytic treatment, and to determine
      whether thrombolysis is a predictor of VN. The study group consisted of 77 RH
      infarct patients. VN was evaluated with six conventional subtests of the
      Behavioural Inattention Test (BIT). Stroke severity was assessed using the
      National Institute of Health Stroke Scale (NIHSS). In the neuropsychological
      examination, 22% of all RH stroke patients had VN. VN was present in 15% of the
      patients in the T+ group and in 28% of the patients in the T- group, but the
      difference was not statistically significant. Despite that, patients in the T-
      group had a higher risk of VN than patients in the T+ group. Our results suggest
      that thrombolysis independently predicted absence of VN.

PMID- 22454607
TI  - The use of clay-polymer nanocomposites in wastewater pretreatment.
AB  - Some agricultural effluents are unsuitable for discharge into standard sewage
      treatment plants: their pretreatment is necessary to avoid clogging of the
      filtering devices by colloidal matter. The colloidal stability of the effluents
      is mainly due to mutual repulsive forces that keep charged particles in
      suspension. Pretreatment processes are based on two separate stages: (a)
      neutralization of the charges ("coagulation") and (b) bridging between several
      small particles to form larger aggregates that sink, leaving clarified effluent
      ("flocculation"). The consequent destabilization of the colloidal suspension
      lowers total suspended solids (TSSs), turbidity, and other environmental quality
      parameters, making the treatments that follow more efficient. Clay-based
      materials have been widely used for effluent pretreatment and pollutant removal.
      This study presents the use of nanocomposites, comprised of an anchoring particle
      and a polymer, as "coagoflocculants" for the efficient and rapid reduction of TSS
      and turbidity in wastewater with a high organic load. The use of such particles
      combines the advantages of coagulant and flocculant by neutralizing the charge of
      the suspended particles while bridging between them and anchoring them to a
      denser particle (the clay mineral), enhancing their precipitation. Very rapid and
      efficient pretreatment is achieved in one single treatment step.

PMID- 22454608
TI  - Coevolution of aah: a dps-like gene with the host bacterium revealed by
      comparative genomic analysis.
AB  - A protein named AAH was isolated from the bacterium Microbacterium arborescens
      SE14, a gut commensal of the lepidopteran larvae. It showed not only a high
      sequence similarity to Dps-like proteins (DNA-binding proteins from starved cell)
      but also reversible hydrolase activity. A comparative genomic analysis was
      performed to gain more insights into its evolution. The GC profile of the aah
      gene indicated that it was evolved from a low GC ancestor. Its stop codon usage
      was also different from the general pattern of Actinobacterial genomes. The
      phylogeny of dps-like proteins showed strong correlation with the phylogeny of
      host bacteria. A conserved genomic synteny was identified in some taxonomically
      related Actinobacteria, suggesting that the ancestor genes had incorporated into
      the genome before the divergence of Micrococcineae from other families. The aah
      gene had evolved new function but still retained the typical dodecameric
      structure.

PMID- 22454609
TI  - Conservative management of keratocystic odontogenic tumors of jaws.
AB  - PURPOSE: The aim of this study was to evaluate different surgical treatment
      methods for keratocystic odontogenic tumors (KCOTs) and the outcome of those
      treatments over a 9-year period. PATIENTS AND METHODS: A retrospective review was
      performed on 43 KCOTs in 39 patients. In radiographic evaluations for diagnosis,
      follow ups and before and after treatment, panoramic, 3D CT and MR images were
      used. The three groups of different surgical treatment were (1) enucleation for
      small unilocular lesions without certainty of histology; (2) enucleation with
      Carnoy's solution, for small unilocular lesions after previous histological
      confirmation of KOCT; (3) marsupialization followed by enucleation with Carnoy's
      solution implemented for large often multilocular KCOTs with intact or
      destruction of cortical bone without infiltration of neighbouring tissue.
      RESULTS: 43 KCOT cases were mostly localized in mandible (76.7%), radiologically
      unilocular (72%), and parakeratocysts (88.4%). Inflammation and satellite cysts
      (daughter cysts) were detected histopathologically in 14 (32.5%) and 7 (16.3%),
      respectively. Among the 43 cysts, 20 (46.5%) were associated with the impacted
      third molar and of 21 (48.8%) was in tooth bearing area, and 5 (11, 6%) located
      on edentulous areas. It was located mostly in the anterior region of maxilla
      (90%) and in mandibular molar and ramus (62.8%). The treatments of KCOTs were 18
      (41.9%) for group 1, and 10 (23.3%) group 2, and 15 (34.8%) group 3. A
      statistically significant relationship was found between the radiographic
      appearance and treatment methods (P = 0.00). No recurrence was found on 40.54 +/-
      23.02 months follow up. CONCLUSION: We concluded that successful treatment
      methods were enucleation and Carnoy's solution in small lesions and
      marsupialization in lesions that have reached a very large size, but because KCOT
      was observed in second decade mostly, long-term follows up are suggested.

PMID- 22454610
TI  - Evaluation of the oxidative effect of long-term repetitive hyperbaric oxygen
      exposures on different brain regions of rats.
AB  - Hyperbaric oxygen (HBO(2)) exposure affects both oxidative and antioxidant
      systems. This effect is positively correlated with the exposure time and duration
      of the treatment. The present study aims enlightening the relation of HBO(2) with
      oxidative/antioxidant systems when administered in a prolonged and repetitive
      manner in brain tissues of rats. Sixty rats were divided into 6 study (n = 8 for
      each) and 1 control (n = 12) group. Rats in the study groups were daily exposed
      90-min HBO(2) sessions at 2.8 ATA for 5, 10, 15, 20, 30 and 40 days. One day
      after the last session, animals were sacrificed; their whole brain tissue was
      harvested and dissected into three different regions as the outer grey matter
      (cortex), the inner white matter and cerebellum. Levels of lipid peroxidation and
      protein oxidation and activities of superoxide dismutase and glutathione
      peroxidase were measured in these tissues. Malondialdehyde, carbonylated protein
      and glutathione peroxidase levels were found to be insignificantly increased at
      different time-points in the cerebral cortex, inner white matter and cerebellum,
      respectively. These comparable results provide evidence for the safety of HBO
      treatments and/or successful adaptive mechanisms at least in the brain tissue of
      rats, even when administered for longer periods.

PMID- 22454611
TI  - Ammonia volatilization from urea-application influenced germination and early
      seedling growth of dry direct-seeded rice.
AB  - Poor seed germination and early seedling growth associated with urea-induced soil
      ammonia volatilization are major constraints in the adoption of dry direct-seeded
      rice. To directly examine soil ammonia volatilization and its damage to seed
      germination and early seedling growth of dry direct-seeded rice when urea is
      applied at seeding, two Petri-dish incubation experiments and a field experiment
      were conducted. Ammonia volatilization due to urea application significantly
      reduced seed germination and early seedling growth of dry direct-seedling rice.
      NBPT significantly reduced ammonia volatilization following urea application. The
      application of ammonium sulfate, instead of urea at seeding, may mitigate poor
      crop establishment of dry direct-seeded rice. Root growth of dry direct-seeded
      rice was more seriously inhibited by soil ammonia volatilization than that of
      shoot. Results suggest that roots are more sensitive to soil ammonia toxicity
      than shoots in dry direct-seeded rice system when N is applied as urea at
      seeding.

PMID- 22454612
TI  - Distribution of BoLA-DRB3 allelic frequencies and identification of two new
      alleles in Iranian buffalo breed.
AB  - The role of the major histocompatibility complex (MHC) in the immune response
      makes it an attractive candidate gene for associations with disease resistance
      and susceptibility. This study describes genetic variability in the BoLA-DRB3 in
      Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency
      of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd
      (12 alleles). Almost 63.50% of the alleles were accounted for by four alleles
      (BoLA-DRB3.2 *48, *20, *21, and obe) in Iranian buffalo. The DRB3.2 *48 allele
      frequency (24.20%) was higher than the others. The frequencies of the DRB3.2 *20
      and DRB3.2 *21 are 14.52 and 14.00, respectively, and obe and gbb have a new
      pattern. Significant distinctions have been found between Iranian buffalo and
      other cattle breed studied. In the Iranian buffaloes studied alleles associated
      with resistance to various diseases are found.

PMID- 22454614
TI  - Chlorine dioxide-iodide-methyl acetoacetate oscillation reaction investigated by
      UV-vis and online FTIR spectrophotometric method.
AB  - In order to study the chemical oscillatory behavior and mechanism of a new
      chlorine dioxide-iodide ion-methyl acetoacetate reaction system, a series of
      experiments were done by using UV-Vis and online FTIR spectrophotometric method.
      The initial concentrations of methyl acetoacetate, chlorine dioxide, potassium
      iodide, and sulfuric acid and the pH value have great influence on the
      oscillation observed at wavelength of 289 nm. There is a preoscillatory or
      induction period, and the amplitude and the number of oscillations are associated
      with the initial concentration of reactants. The equations for the triiodide ion
      reaction rate changing with reaction time and the initial concentrations in the
      oscillation stage were obtained. Oscillation reaction can be accelerated by
      increasing temperature. The apparent activation energies in terms of the
      induction period and the oscillation period were 26.02 KJ/mol and 17.65 KJ/mol,
      respectively. The intermediates were detected by the online FTIR analysis. Based
      upon the experimental data in this work and in the literature, a plausible
      reaction mechanism was proposed for the oscillation reaction.

PMID- 22454615
TI  - B cell responses to CpG correlate with CXCL16 expression levels in common
      variable immunodeficiency.
AB  - Broad Toll-like receptor 9 (TLR9) signalling defects after CpG in vitro
      stimulation have been described in common variable immunodeficiency (CVID).
      CXCL16, a surface receptor, was recently shown to influence cell responses to
      CpG. We evaluated the expression and function of CXCL16 on B cells from healthy
      controls and CVID patients. We report that CXCL16 is normally expressed on B
      cells throughout peripheral maturation. Decreased B cell expression of CXCL16 was
      observed in a subgroup of CVID patients that correlated with defective in vitro
      responses to CpG (such as upregulation of CD69, CD86, AICDA, IL-6, and TLR9). Our
      data suggest that expression levels of a surface receptor, namely, CXCL16,
      correlate with B cell responses mediated by TLR9 in common variable
      immunodeficiency.

PMID- 22454616
TI  - The role of reward in dynamic decision making.
AB  - The present study investigates two aspects of decision making that have yet to be
      explored within a dynamic environment, (1) comparing the accuracy of cue-outcome
      knowledge under conditions in which knowledge acquisition is either through
      Prediction or Choice, and (2) examining the effects of reward on both Prediction
      and Choice. In the present study participants either learnt about the cue-outcome
      relations in the environment by choosing cue values in order to maintain an
      outcome to criterion (Choice-based decision making), or learnt to predict the
      outcome from seeing changes to the cue values (Prediction-based decision making).
      During training participants received outcome feedback and one of four types of
      reward manipulations: Positive Reward, Negative Reward, Both Positive + Negative
      Reward, No Reward. After training both groups of learners were tested on
      prediction and choice-based tasks. In the main, the findings revealed that cue
      outcome knowledge was more accurate when knowledge acquisition was Choice-based
      rather than Prediction-based. During learning Negative Reward adversely affected
      Choice-based decision making while Positive Reward adversely affected predictive
      based decision making. During the test phase only performance on tests of choice
      was adversely affected by having received Positive Reward or Negative Reward
      during training. This article proposes that the adverse effects of reward may
      reflect the additional demands placed on processing rewards which compete for
      cognitive resources required to perform the main goal of the task. This in turn
      implies that, rather than facilitate decision making, the presentation of rewards
      can interfere with Choice-based and Prediction-based decisions.

PMID- 22454613
TI  - Yeast as a tool to study signaling pathways in mitochondrial stress response and
      cytoprotection.
AB  - Cell homeostasis results from the balance between cell capability to adapt or
      succumb to environmental stress. Mitochondria, in addition to supplying cellular
      energy, are involved in a range of processes deciding about cellular life or
      death. The crucial role of mitochondria in cell death is well recognized.
      Mitochondrial dysfunction has been associated with the death process and the
      onset of numerous diseases. Yet, mitochondrial involvement in cellular adaptation
      to stress is still largely unexplored. Strong interest exists in pharmacological
      manipulation of mitochondrial metabolism and signaling. The yeast Saccharomyces
      cerevisiae has proven a valuable model organism in which several intracellular
      processes have been characterized in great detail, including the retrograde
      response to mitochondrial dysfunction and, more recently, programmed cell death.
      In this paper we review experimental evidences of mitochondrial involvement in
      cytoprotection and propose yeast as a model system to investigate the role of
      mitochondria in the cross-talk between prosurvival and prodeath pathways.

PMID- 22454617
TI  - Steroid modulation of hippocampal plasticity: switching between cognitive and
      emotional memories.
AB  - Several new observations have shifted the view of the hippocampus from a
      structure in charge of cognitive processes to a brain area that participates in
      the formation of emotional memories, in addition to its role in cognition.
      Specifically, while the dorsal hippocampus is involved in the processing of
      cognitive memories; the ventral sector is mainly associated with the control of
      behavioral inhibition, stress, and emotional memory. Stress is likely to cause
      this switch in control of hippocampal functions by modulating synaptic plasticity
      in the dorsal and ventral sectors of the hippocampus through the differential
      activation of mineralocorticosteroid or glucocorticosteroid receptors. Herein, we
      will review the effects of stress hormones on synaptic plasticity in the
      hippocampus and outline the outcomes on stress-related global functions of this
      structure. We propose that steroid hormones act as molecular switches: by
      changing the strength of synaptic connectivity in the hippocampus following
      stress, they regulate the routes by which the hippocampus is functionally linked
      to the rest of the brain. This hypothesis has profound implications for the
      pathophysiology of psychiatric disorders.

PMID- 22454618
TI  - Vestibular and attractor network basis of the head direction cell signal in
      subcortical circuits.
AB  - Accurate navigation depends on a network of neural systems that encode the moment
      to-moment changes in an animal's directional orientation and location in space.
      Within this navigation system are head direction (HD) cells, which fire
      persistently when an animal's head is pointed in a particular direction (Sharp et
      al., 2001a; Taube, 2007). HD cells are widely thought to underlie an animal's
      sense of spatial orientation, and research over the last 25+ years has revealed
      that this robust spatial signal is widely distributed across subcortical and
      cortical limbic areas. The purpose of the present review is to summarize some of
      the recent studies arguing that the origin of the HD signal resides
      subcortically, specifically within the reciprocal connections of the dorsal
      tegmental and lateral mammillary nuclei. Furthermore, we review recent work
      identifying "bursting" cellular activity in the HD cell circuit after lesions of
      the vestibular system, and relate these observations to the long held view that
      attractor network mechanisms underlie HD signal generation. Finally, we summarize
      anatomical and physiological work suggesting that this attractor network
      architecture may reside within the tegmento-mammillary circuit.

PMID- 22454619
TI  - Selective serotonergic excitation of callosal projection neurons.
AB  - Serotonin (5-HT) acting as a neurotransmitter in the cerebral cortex is critical
      for cognitive function, yet how 5-HT regulates information processing in cortical
      circuits is not well understood. We tested the serotonergic responsiveness of
      layer 5 pyramidal neurons (L5PNs) in the mouse medial prefrontal cortex (mPFC),
      and found three distinct response types: long-lasting 5-HT(1A) (1A) receptor
      dependent inhibitory responses (84% of L5PNs), 5-HT(2A) (2A) receptor-dependent
      excitatory responses (9%), and biphasic responses in which 2A-dependent
      excitation followed brief inhibition (5%). Relative to 5-HT-inhibited neurons,
      those excited by 5-HT had physiological properties characteristic of
      callosal/commissural (COM) neurons that project to the contralateral cortex. We
      tested whether serotonergic responses in cortical pyramidal neurons are
      correlated with their axonal projection pattern using retrograde fluorescent
      labeling of COM and corticopontine-projecting (CPn) neurons. 5-HT generated
      excitatory or biphasic responses in all 5-HT-responsive layer 5 COM neurons.
      Conversely, CPn neurons were universally inhibited by 5-HT. Serotonergic
      excitation of COM neurons was blocked by the 2A antagonist MDL 11939, while
      serotonergic inhibition of CPn neurons was blocked by the 1A antagonist WAY
      100635, confirming a role for these two receptor subtypes in regulating pyramidal
      neuron activity. Selective serotonergic excitation of COM neurons was not layer
      specific, as COM neurons in layer 2/3 were also selectively excited by 5-HT
      relative to their non-labeled pyramidal neuron neighbors. Because neocortical 2A
      receptors are implicated in the etiology and pathophysiology of schizophrenia, we
      propose that COM neurons may represent a novel cellular target for intervention
      in psychiatric disease.

PMID- 22454621
TI  - Automatic human interaction understanding: lessons from a multidisciplinary
      approach.

PMID- 22454620
TI  - The endocannabinoid transport inhibitor AM404 differentially modulates
      recognition memory in rats depending on environmental aversiveness.
AB  - Cannabinoid compounds may influence both emotional and cognitive processes
      depending on the level of environmental aversiveness at the time of drug
      administration. However, the mechanisms responsible for these responses remain to
      be elucidated. The present experiments investigated the effects induced by the
      endocannabinoid transport inhibitor AM404 (0.5-5 mg/kg, i.p.) on both emotional
      and cognitive performances of rats tested in a Spatial Open Field task and
      subjected to different experimental settings, named High Arousal (HA) and Low
      Arousal (LA) conditions. The two different experimental conditions influenced
      emotional reactivity independently of drug administration. Indeed, vehicle
      treated rats exposed to the LA condition spent more time in the center of the
      arena than vehicle-treated rats exposed to the HA context. Conversely, the
      different arousal conditions did not affect the cognitive performances of vehicle
      treated animals such as the capability to discriminate a spatial displacement of
      the objects or an object substitution. AM404 administration did not alter
      locomotor activity or emotional behavior of animals exposed to both environmental
      conditions. Interestingly, AM404 administration influenced the cognitive
      parameters depending on the level of emotional arousal: it impaired the
      capability of rats exposed to the HA condition to recognize a novel object while
      it did not induce any impairing effect in rats exposed to the LA condition. These
      findings suggest that drugs enhancing endocannabinoid signaling induce different
      effects on recognition memory performance depending on the level of emotional
      arousal induced by the environmental conditions.

PMID- 22454622
TI  - Desynchronizing electrical and sensory coordinated reset neuromodulation.
AB  - Coordinated reset (CR) stimulation is a desynchronizing stimulation technique
      based on timely coordinated phase resets of sub-populations of a synchronized
      neuronal ensemble. It has initially been computationally developed for electrical
      deep brain stimulation (DBS), to enable an effective desynchronization and
      unlearning of pathological synchrony and connectivity (anti-kindling). Here we
      computationally show for ensembles of spiking and bursting model neurons
      interacting via excitatory and inhibitory adaptive synapses that a phase reset of
      neuronal populations as well as a desynchronization and an anti-kindling can
      robustly be achieved by direct electrical stimulation or indirect (synaptically
      mediated) excitatory and inhibitory stimulation. Our findings are relevant for
      DBS as well as for sensory stimulation in neurological disorders characterized by
      pathological neuronal synchrony. Based on the obtained results, we may expect
      that the local effects in the vicinity of a depth electrode (realized by direct
      stimulation of the neurons' somata or stimulation of axon terminals) and the non
      local CR effects (realized by stimulation of excitatory or inhibitory efferent
      fibers) of deep brain CR neuromodulation may be similar or even identical.
      Furthermore, our results indicate that an effective desynchronization and anti
      kindling can even be achieved by non-invasive, sensory CR neuromodulation. We
      discuss the concept of sensory CR neuromodulation in the context of neurological
      disorders.

PMID- 22454623
TI  - Larval Habitat Associations with Human Land Uses, Roads, Rivers, and Land Cover
      for Anopheles albimanus, A. pseudopunctipennis, and A. punctimacula (Diptera:
      Culicidae) in Coastal and Highland Ecuador.
AB  - Larval habitat for three highland Anopheles species: Anopheles albimanus
      Wiedemann, Anopheles pseudopunctipennis Theobald, and Anopheles punctimacula Dyar
      and Knab was related to human land uses, rivers, roads, and remotely sensed land
      cover classifications in the western Ecuadorian Andes. Of the five commonly
      observed human land uses, cattle pasture (n = 30) provided potentially suitable
      habitat for A. punctimacula and A. albimanus in less than 14% of sites, and was
      related in a principal components analysis (PCA) to the presence of macrophyte
      vegetation, greater surface area, clarity, and algae cover. Empty lots (n = 30)
      were related in the PCA to incident sunlight and provided potential habitat for
      A. pseudopunctipennis and A. albimanus in less than 14% of sites. The other land
      uses surveyed (banana, sugarcane, and mixed tree plantations; n = 28, 21, 25,
      respectively) provided very little standing water that could potentially be used
      for larval habitat. River edges and eddies (n = 41) were associated with greater
      clarity, depth, temperature, and algae cover, which provide potentially suitable
      habitat for A. albimanus in 58% of sites and A. pseudopunctipennis in 29% of
      sites. Road-associated water bodies (n = 38) provided potential habitat for A.
      punctimacula in 44% of sites and A. albimanus in 26% of sites surveyed. Species
      collection localities were compared to land cover classifications using
      Geographic Information Systems software. All three mosquito species were
      associated more often with the category "closed/open broadleaved evergreen and/or
      semi-deciduous forests" than expected (P <= 0.01 in all cases), given such a
      habitat's abundance. This study provides evidence that specific human land uses
      create habitat for potential malaria vectors in highland regions of the Andes.

PMID- 22454624
TI  - Sleep Disturbances in Pediatric Bipolar Disorder: A Comparison between Bipolar I
      and Bipolar NOS.
AB  - INTRODUCTION: The diagnosis of bipolar disorder (BD) in youths has been
      controversial, especially for the subtype BD not otherwise specified (BD-NOS). In
      spite of growing evidence that sleep is a core feature of BD, few studies
      characterize and compare sleep disturbances in youth with BD type I (BD-I) and BD
      NOS. Sleep disturbances are frequently reported in clinical descriptions of
      children and adolescents with BD, however the reporting of the frequency and
      characteristics of sleep symptoms in youth with BD-NOS and BD-I during episodes
      remain poor. This study compares symptom of sleep disturbance as occurring in
      manic and depressive episodes in BD-I and BD-NOS youth using Kiddie-schedule for
      affective disorders and schizophrenia, present and lifetime version (K-SADS-PL)
      interview data. The study also addresses whether symptoms of sleep disturbance
      vary in different age groups. MATERIALS AND METHODS: The sample consisted of 70
      children and adolescent outpatients at an urban specialty clinic (42M/28F, 10.8
      +/- 3.6 years old) including 24 BD-I and 46 BD-NOS assessed using K-SADS-PL
      parent interview. RESULTS: Sleep disturbances including insomnia and decreased
      need for sleep were reported by 84.3% of the sample. Enuresis was diagnosed in
      27% of sample. There were no significant differences in frequency of sleep
      symptoms between BD-I and BD-NOS. Regardless of BD subtype, current functioning
      was negatively correlated with decreased need for sleep but not insomnia, and
      regardless of BD subtype. CONCLUSION: The majority of youth with BD presents with
      sleep symptoms during mood episodes. BD-NOS presents with the same proportion of
      sleep symptoms as BD-I in our sample.

PMID- 22454625
TI  - How does language change perception: a cautionary note.
AB  - The relationship of language, perception, and action has been the focus of recent
      studies exploring the representation of conceptual knowledge. A substantial
      literature has emerged, providing ample demonstrations of the intimate
      relationship between language and perception. The appropriate characterization of
      these interactions remains an important challenge. Recent evidence involving
      visual search tasks has led to the hypothesis that top-down input from linguistic
      representations may sharpen visual feature detectors, suggesting a direct
      influence of language on early visual perception. We present two experiments to
      explore this hypothesis. Experiment 1 demonstrates that the benefits of
      linguistic priming in visual search may arise from a reduction in the demands on
      working memory. Experiment 2 presents a situation in which visual search
      performance is disrupted by the automatic activation of irrelevant linguistic
      representations, a result consistent with the idea that linguistic and sensory
      representations interact at a late, response-selection stage of processing. These
      results raise a cautionary note: While language can influence performance on a
      visual search, the influence need not arise from a change in perception per se.

PMID- 22454626
TI  - Contribution of MS-Based Proteomics to the Understanding of Herpes Simplex Virus
      Type 1 Interaction with Host Cells.
AB  - Like other DNA viruses, herpes simplex virus type 1 (HSV-1) replicates and
      proliferates in host cells continuously modulating the host molecular
      environment. Following a sophisticated temporal expression pattern, HSV-1 encodes
      at least 89 multifunctional proteins that interplay with and modify the host cell
      proteome. During the last decade, advances in mass spectrometry applications
      coupled to the development of proteomic separation methods have allowed to
      partially monitor the impact of HSV-1 infection in human cells. In this review,
      we discuss the current use of different proteome fractionation strategies to
      define HSV-1 targets in two major application areas: (i) viral-protein
      interactomics to decipher viral-protein interactions in host cells and (ii)
      differential quantitative proteomics to analyze the virally induced changes in
      the cellular proteome. Moreover, we will also discuss the potential application
      of high-throughput proteomic approaches to study global proteome dynamics and
      also post-translational modifications in HSV-1-infected cells that will greatly
      improve our molecular knowledge of HSV-1 infection.

PMID- 22454627
TI  - The role of endoplasmic reticulum stress in autoimmune-mediated beta-cell
      destruction in type 1 diabetes.
AB  - Unlike type 2 diabetes which is caused by the loss of insulin sensitivity, type 1
      diabetes (T1D) is manifested by the absolute deficiency of insulin secretion due
      to the loss of beta mass by autoimmune response against beta-cell self-antigens.
      Although significant advancement has been made in understanding the pathoetiology
      for type 1 diabetes, the exact mechanisms underlying autoimmune-mediated beta
      cell destruction, however, are yet to be fully addressed. Accumulated evidence
      demonstrates that endoplasmic reticulum (ER) stress plays an essential role in
      autoimmune-mediated beta-cell destruction. There is also evidence supporting that
      ER stress regulates the functionality of immune cells relevant to autoimmune
      progression during T1D development. In this paper, we intend to address the role
      of ER stress in autoimmune-mediated beta-cell destruction during the course of
      type 1 diabetes. The potential implication of ER stress in modulating autoimmune
      response will be also discussed. We will further dissect the possible pathways
      implicated in the induction of ER stress and summarize the potential mechanisms
      underlying ER stress for mediation of beta-cell destruction. A better
      understanding of the role for ER stress in T1D pathoetiology would have great
      potential aimed at developing effective therapeutic approaches for the
      prevention/intervention of this devastating disorder.

PMID- 22454629
TI  - Oxidative metabolism genes are not responsive to oxidative stress in rodent Beta
      cell lines.
AB  - Altered expression of oxidative metabolism genes has been described in the
      skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells
      contain low levels of antioxidant enzymes and are particularly susceptible to
      oxidative stress. In this study, we explored the effect of hyperglycemia-induced
      oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell
      line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L), ambient (11
      mmol/L), and high (28 mmol/L) glucose conditions for 48 hours. Increases in
      oxidative stress were measured using the fluorescent probe dihydrorhodamine 123.
      We then measured the expression levels of a panel of 90 oxidative metabolism
      genes by real-time PCR. Elevated reactive oxygen species (ROS) production was
      evident in INS-1 cells after 48 hours (P < 0.05). TLDA analysis revealed a
      significant (P < 0.05) upregulation of 16 of the 90 genes under hyperglycemic
      conditions, although these expression differences did not reflect differences in
      ROS. We conclude that although altered glycemia may influence the expression of
      some oxidative metabolism genes, this effect is probably not mediated by
      increased ROS production. The alterations to the expression of oxidative
      metabolism genes previously observed in human diabetic skeletal muscle do not
      appear to be mirrored in rodent pancreatic beta cells.

PMID- 22454628
TI  - Signaling mechanisms in the regulation of renal matrix metabolism in diabetes.
AB  - Renal hypertrophy and accumulation of extracellular matrix proteins are among
      cardinal manifestations of diabetic nephropathy. TGF beta system has been
      implicated in the pathogenesis of these manifestations. Among signaling pathways
      activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin
      )regulated pathways are pivotal in orchestrating high glucose-induced production
      of ECM proteins leading to functional and structural changes in the kidney
      culminating in adverse outcomes. Understanding signaling pathways that influence
      individual matrix protein expression could lead to the development of new
      interventional strategies. This paper will highlight some of the diverse
      components of the signaling network stimulated by hyperglycemia with an emphasis
      on extracellular matrix protein metabolism in the kidney in diabetes.

PMID- 22454630
TI  - Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing
      Ang-1/Tie-2 signaling in diabetes.
AB  - Diabetes is associated with impairment of angiogenesis such as reduction of
      myocardial capillary formation. Our previous studies demonstrate that disruption
      of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes
      associated impairment of angiogenesis. Protein tyrosine phosphatase (PTP) has a
      critical role in the regulation of insulin signal by inhibition of tyrosine
      kinase phosphorylation. In present study, we examined the role of protein
      tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2
      angiogenic signaling and angiogenesis. SHP-1 expression was significantly
      increased in diabetic db/db mouse hearts. Furthermore, SHP-1 bond to Tie-2
      receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse
      heart microvascular endothelial cell (MHMEC). Exposure of MHMEC to high glucose
      (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant
      reduction of Tie-2 phosphorylation. Exposure of MHMEC to HG also blunted Ang-1
      mediated SHP-1/Tie-2 dissociation. Knockdown of SHP-1 significantly attenuated HG
      induced caspase-3 activation and apoptosis in MHMEC. Treatment with PTP
      inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis. Our
      data implicate a critical role of SHP-1 in diabetes-associated vascular
      complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1
      should be considered as a new therapeutic strategy for the treatment of diabetes
      associated impairment of angiogenesis.

PMID- 22454631
TI  - Association of FTO polymorphisms with early age of obesity in obese Italian
      subjects.
AB  - Obesity is recognized as a major health problem worldwide. Genetic factors play a
      major role in obesity, and genomewide association studies have provided evidence
      that several common variants within the fat mass- and obesity-associated (FTO)
      gene are significantly associated with obesity. Very limited data is available on
      FTO in the Italian population. Aims of our study are to investigate: (1) the
      association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI)
      and obesity-related parameters in a large cohort (n = 752) of Italian obese
      subjects; (2) the association between the two FTO SNPs and age of onset of
      obesity. Our results demonstrate a strong association between FTO SNPs rs9939609
      (P < 0.043) and rs9930506 (P < 0.029) with BMI in the Italian population. FTO
      rs9930506 was significantly associated with higher BMI in a G allele dose
      dependent manner (BMI + 1.4 kg/m2 per G allele). We also observed that the
      association with BMI of the two FTO variants varied with age, with the carriers
      of the risk alleles developing an increase in body weight earlier in life. In
      conclusion, our study further demonstrates a role of the genetic variability in
      FTO on BMI in a large Italian population.

PMID- 22454633
TI  - Quality of life in Iranian patients with acne.
AB  - Acne is a chronic inflammatory disease of pilosebaceous units. Although the acne
      isnot a life threatening disease, studies have revealed that it has significant
      effect on self-image and quality of life. The purpose of this paper was to
      investigate the health-related quality of life in patients with acne in an
      Iranian context. Dermatology Life Quality Index (DLQI) and Cardiff Acne
      Disability Index (CADI) were used for measuring quality of life, and severity of
      acne was measured by Global Acne Grading System (GAGS). The mean (+/-SD) of DLQI
      and CADI scores was 6.42 (+/-4.77) and 5.97 (+/-2.97), respectively. Acne
      influenced the quality of life in 51.8% of patients from moderate to very much,
      and the quality of life was affected by the severity of acne (P < 0.01). Since
      acne has significant effects on patient's quality of life, the management of
      patients with acne requires more attention to different aspects of quality of
      life.

PMID- 22454632
TI  - Role of forkhead transcription factors in diabetes-induced oxidative stress.
AB  - Diabetes is a chronic metabolic disorder, characterized by hyperglycemia
      resulting from insulin deficiency and/or insulin resistance. Recent evidence
      suggests that high levels of reactive oxygen species (ROS) and subsequent
      oxidative stress are key contributors in the development of diabetic
      complications. The FOXO family of forkhead transcription factors including FOXO1,
      FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular
      and biological processes and are critical regulators of cellular oxidative stress
      response pathways. FOXO1 transcription factors can affect a number of different
      tissues including liver, retina, bone, and cell types ranging from hepatocytes to
      microvascular endothelial cells and pericytes to osteoblasts. They are induced by
      oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this
      paper, we discuss the role of FOXO transcription factors in mediating oxidative
      stress-induced cellular response.

PMID- 22454634
TI  - Nail isthmus: a distinct region of the nail apparatus.
AB  - The nail unit is constructed by distinctly regulated components. The nail isthmus
      is a lately proposed region as a transitional zone between the most distal part
      of the nail bed and the hyponychium. It is difficult to recognize the nail
      isthmus in the normal nail, but it is easy to identify the region in nail
      disorders such as pterygium inversum unguis and ectopic nail. We describe
      structure and putative function of the nail isthmus via histopathologic features
      of pterygium inversum unguis and ectopic nail.

PMID- 22454635
TI  - Preclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway.
AB  - Knowledge gained from the identification of genetic and epigenetic alterations
      that contribute to the progression of prostate cancer in humans is now being
      implemented in the development of functionally relevant translational models. GEM
      (genetically modified mouse) models are being developed to incorporate the same
      molecular defects associated with human prostate cancer. Haploinsufficiency is
      common in prostate cancer and homozygous loss of PTEN is strongly correlated with
      advanced disease. In this paper, we discuss the evolution of the PTEN knockout
      mouse and the cooperation between PTEN and other genetic alterations in tumor
      development and progression. Additionally, we will outline key points that make
      these models key players in the development of personalized medicine, as
      potential tools for target and biomarker development and validation as well as
      models for drug discovery.

PMID- 22454636
TI  - An Adult Patient with Fontan Physiology: A TEE Perspective.
AB  - Fontan and Baudet described in 1971 the separation of the pulmonary and systemic
      circulations resulting in univentricular physiology. The evolution of the Fontan
      procedure, most notably the substitution of right atrial-to-pulmonary artery
      anastomosis with cavopulmonary connections, resulted in significantly improved
      late outcomes. Many patients survive well into adulthood and are able to lead
      productive lives. While ideally under medical care at specialized centers for
      adult congenital cardiac pathology, these patients may present to the outside
      hospitals for emergency surgery, electrophysiologic interventions, and pregnancy.
      This presentation presents a "train of thought," linking the TEE images to the
      perioperative physiologic considerations faced by an anesthesiologist caring for
      a patient with Fontan circulation in the perioperative settings. Relevant effects
      of mechanical ventilation on pulmonary vascular resistance, pulmonary blood flow
      and cardiac preload, presence of coagulopathy and thromboembolic potential,
      danger of abrupt changes of systemic vascular resistance and systemic venous
      return are discussed.

PMID- 22454639
TI  - The symptom and genetic diversity of cassava brown streak viruses infecting
      cassava in East Africa.
AB  - The genetic and symptom diversity of six virus isolates causing cassava brown
      streak disease (CBSD) in the endemic (Kenya, Mozambique, and Tanzania) and the
      recently affected epidemic areas (Uganda) of eastern Africa was studied. Five
      cassava varieties; Albert, Colombian, Ebwanateraka, TMS60444 (all susceptible)
      and Kiroba (tolerant) were graft inoculated with each isolate. Based on a number
      of parameters including the severity of leaf and root symptoms, and the extent of
      virus transmission by grafting, the viruses were classified as either severe or
      relatively mild. These results were further confirmed by the mechanical
      inoculation of 13 herbaceous hosts in which the virulent isolates caused plant
      death in Nicotiana clevelandii and N. benthamiana whereas the milder isolates did
      not. Phylogenetic analysis of complete coat protein gene sequences of these
      isolates together with sequences obtained from 14 other field-collected samples
      from Kenya and Zanzibar, and reference sequences grouped them into two distinct
      clusters, representing the two species of cassava brown streak viruses. Put
      together, these results did not suggest the association of a hypervirulent form
      of the virus with the current CBSD epidemic in Uganda. Identification of the
      severe and milder isolates, however, has further implications for disease
      management and quarantine requirements.

PMID- 22454638
TI  - Neutropenia Prediction Based on First-Cycle Blood Counts Using a FOS-3NN
      Classifier.
AB  - Background. Delivery of full doses of adjuvant chemotherapy on schedule is key to
      optimal breast cancer outcomes. Neutropenia is a serious complication of
      chemotherapy and a common barrier to this goal, leading to dose reductions or
      delays in treatment. While past research has observed correlations between
      complete blood count data and neutropenic events, a reliable method of
      classifying breast cancer patients into low- and high-risk groups remains
      elusive. Patients and Methods. Thirty-five patients receiving adjuvant
      chemotherapy for early-stage breast cancer under the care of a single oncologist
      are examined in this study. FOS-3NN stratifies patient risk based on complete
      blood count data after the first cycle of treatment. All classifications are
      independent of breast cancer subtype and clinical markers, with risk level
      determined by the kinetics of patient blood count response to the first cycle of
      treatment. Results. In an independent test set of patients unseen by FOS-3NN, 19
      out of 21 patients were correctly classified (Fisher's exact test probability P <
      0.00023 [2 tailed], Matthews' correlation coefficient +0.83). Conclusions. We
      have developed a model that accurately predicts neutropenic events in a
      population treated with adjuvant chemotherapy in the first cycle of a 6-cycle
      treatment.

PMID- 22454640
TI  - TB Peritonitis Mistaken for Ovarian Carcinomatosis Based on an Elevated CA-125.
AB  - Background. In the United States, tuberculosis (TB) is of relatively low
      prevalence and most newly diagnosed patients are born outside of the United
      States. In addition, a large percentage (20.6%) of TB cases initially present
      with extrapulmonary manifestations (CDC, 2010). Cases of TB peritonitis are a
      diagnostic challenge in women due to the nonspecific clinical features
      overlapping with signs of ovarian cancer. (Kosseifi et al., 2009; Rashed et al.,
      2007; and Xi et al., 2010). We present a 27 year-old woman thought to have
      ovarian carcinomatosis based on elevated levels of CA-125 who was ultimately
      diagnosed with TB salpingitis, endometritis, and peritonitis. Methods. This brief
      report is a retrospective case report. Results. This case outlines the
      unfortunate consequences of the misdiagnosis of what probably was an antibiotic
      responsive illness, resulting in an unnecessarily aggressive surgical procedure.
      The delay in the diagnosis of tuberculous pertitonitis resulted in an unnecessary
      radical resection of the patient's reproductive organs. Conclusions. Patients
      with TB peritonitis present with non-specific signs that may be misdiagnoses as
      ovarian cancer. In differentiating between ovarian carcinomatosis and peritoneal
      TB, it is vital to consider country of origin, age, CA-125, ascitic fluid
      analysis, and the use of intra-operative frozen sections.

PMID- 22454637
TI  - Neuroinflammation in the aging down syndrome brain; lessons from Alzheimer's
      disease.
AB  - Down syndrome (DS) is the most genetic cause of mental retardation and is caused
      by the triplication of chromosome 21. In addition to the disabilities caused
      early in life, DS is also noted as causing Alzheimer's-disease-like pathological
      changes in the brain, leading to 50-70% of DS patients showing dementia by 60-70
      years of age. Inflammation is a complex process that has a key role to play in
      the pathogenesis of Alzheimer's disease. There is relatively little understood
      about inflammation in the DS brain and how the genetics of DS may alter this
      inflammatory response and change the course of disease in the DS brain. The goal
      of this review is to highlight our current understanding of inflammation in
      Alzheimer's disease and predict how inflammation may affect the pathology of the
      DS brain based on this information and the known genetic changes that occur due
      to triplication of chromosome 21.

PMID- 22454641
TI  - Right lower quadrant abdominal pain in a patient with prior ventriculoperitoneal
      shunting: consider the tip!
AB  - Introduction. Ventriculoperitoneal (VP) shunting is the treatment of choice for
      nonobstructive hydrocephalus. In patients with such a device, right lower
      quadrant abdominal pain can puzzle the surgeon, posing a differential diagnostic
      problem among appendicitis, nonsurgical colicky pain, and primary shunt catheter
      tip infection. Treatment is different in either case. Presentation of Case. We
      hereby present a case of a young woman with prior ventriculoperitoneal shunt
      positioning who presented to our department with right lower quadrant abdominal
      pain. The patient underwent a 24-hour observation including a neurosurgery
      consult in order to exclude acute appendicitis and VP shunt tip infection. Twenty
      four hours later, the patient's symptomatology improved, and she was discharged
      with the diagnosis of atypical colicky abdominal pain seeking a
      gastroenterologist consult. Discussion. This case supports that when a patient
      with prior VP shunting presents with right lower quadrant abdominal pain,
      differential diagnosis can be tricky for the surgeon. Conclusion. Apart from
      acute appendicitis, primary or secondary VP catheter tip infection must be
      considered because the latter can be disastrous.

PMID- 22454642
TI  - Metastatic renal cell carcinoma to the parotid gland in the setting of chronic
      lymphocytic leukemia.
AB  - Renal cell carcinoma (RCC) is infamous for its unpredictable behavior and
      metastatic potential. We report a case of a patient with a complex history of
      multifocal renal cell carcinoma and chronic lymphocytic leukemia (CLL), who
      subsequently developed a parotid mass. Total parotidectomy revealed this mass to
      be an additional site of metastasis which had developed 19 years after his
      initial diagnosis of RCC.

PMID- 22454643
TI  - A rare case of mucinous adenocarcinoma of the colon presenting as ileoileal
      intussusception in an adult.
AB  - Intussusception is the cause of around 1% of all bowel obstructions in adults.
      Unlike in children, where intussusception is most often idiopathic in nature,
      cases in adults usually have an identifiable etiology, most commonly malignancy.
      Symptoms are usually non-specific, but timely identification and management is
      crucial due to high rates of carcinoma as the lead point of intussusception. Here
      we present a rare case of mucinous adenocarcinoma of the colon that presented as
      ileoileal intussusception. Diagnostic and treatment issues are also discussed.

PMID- 22454644
TI  - Extrapulmonary small cell carcinoma of the anal canal: a case report and review
      of the literature.
AB  - Purpose. Extrapulmonary small cell carcinoma affecting the anal canal is a rare
      and poorly understood entity which can, in its early stages, masquerade as benign
      anorectal disease such as hemorrhoids. Methods. We report a case of this rare
      malignancy which initially presented with hematochezia and anal pain. We also
      review the literature with regard to previously described cases and management
      strategies including the role of surgery. Results. Despite aggressive
      multidisciplinary treatment consisting of chemotherapy and radiation, the disease
      progressed rapidly with dissemination occurring only three months after
      completion of treatment. Because of the aggressive nature of this tumor, the
      treatment options for this almost universally fatal malignancy are often
      palliative in nature. Conclusion. Chemoradiotherapy is likely the most reasonable
      approach to extrapulmonary small cell carcinoma of the anal canal given its
      aggressiveness.

PMID- 22454645
TI  - A unique case of asystole secondary to facial injury.
AB  - Bradycardia has been reported during intraoperative settings of craniofacial,
      cerebropontine angle and trigeminal ganglion surgeries (Schaller et al. (2009,
      1999); Parbhakar et al. (2009); Koerbel et al. (2005); Roberts et al. (1999)). It
      is also commonly seen in children undergoing orbital and maxillary fractures
      repair. This mechanism has been described as the trigeminocardiac reflex (TCR)
      (Schaller et al. (2009, 2004); Kim et al. (2000); Lang et al. (1991); Van
      Brocklin et al. (1982)). We report an unusual case of posttraumatic bradycardia
      and recurrent asystole in a previously healthy adult patient from possible TCR in
      the absence of any surgical intervention to the head and orbital area.

PMID- 22454646
TI  - Brain metastasis of nasopharyngeal carcinoma: a case report and literature
      review.
AB  - Central nervous system metastases from nasopharyngeal carcinoma (NPC) are
      uncommon. The patient presented was diagnosed with aggressive advanced NPC
      resistant to treatment and complicated by a solitary brain metastasis. A PubMed
      database search was conducted to review the existing literature regarding brain
      metastases of NPC, using the search terms "nasopharyngeal neoplasia,"
      "nasopharyngeal carcinoma," "nasopharynx," "radiotherapy," "central nervous
      system," and "brain" in section of "Title/Abstract." The articles were first
      evaluated by title and then by abstract, and thereafter appropriate manuscripts
      were evaluated by full text. References of the published papers were also
      reviewed.

PMID- 22454647
TI  - Giant aortic pseudoaneurysm with stanford type a aortic dissection after aortic
      valve replacement.
AB  - Giant pseudoaneurysm of the ascending aorta is a rare but dreadful complication
      occurring several months or years after aortic surgery. Thoracic aortic aneurysms
      tend to be asymptomatic and were previously often diagnosed only after a
      complication such as dissection or rupture. We present a rare case of giant
      ascending aneurysm with Stanford type A aortic dissection occurring 6 years after
      aortic valve replacement and also illustrate the potential dimensions the
      ascending aorta may reach by a pseudoaneurysm and dissection after AVR.

PMID- 22454648
TI  - Association between a Primitive Brain Tumor and Cerebral Aspergillosis.
AB  - Cerebral aspergillosis is a rare pathology of poor prognosis in spite of the use
      of adapted antifungal treatments. This infection of the central nervous system is
      generally the complication of an invasive aspergillosis with hematogenic
      scattering from pulmonary focal spots. It can arise in immunocompetent patients
      treated with prolonged corticotherapy or chemoradiotherapy for cancer. A case of
      lethal cerebral aspergillosis in a patient with an infiltrative glioma treated
      with corticotherapy and radiotherapy is reported. Clinicopathological aspects and
      therapeutic approach are described.

PMID- 22454649
TI  - Gigant transethmoidal meningoencephalocele operated by full endonasal endoscopic
      approach: case report.
AB  - Intranasal meningoencephaloceles have historically been managed by neurosurgeons,
      although their main clinical manifestations are rhinological. Recent advances in
      endoscopic skull base surgery has significantly improved the treatment of these
      lesions and consequently diminished appreciable surgical morbidity. We report an
      ethmoidal meningoencephalocele case operated on by endonasal endoscopic approach
      for removal of the lesion and reconstructing the associated skull base. From this
      experience, we conclude that removal of the lesion and watertight closure of the
      skull base irrespective of the size of the mass and anterior skull base defect
      are the operation's most important aspects.

PMID- 22454650
TI  - A true aneurysm of the zygomatic orbital artery: first case report in the
      literature.
AB  - A 33-year-old man presented with a pulsatile mass in the left temporal region;
      about 1 year before the current presentation, the swelling had arisen on the
      upper lateral border of the orbital arch and increased in recent months. His
      medical history was negative for accidental or iatrogenic head injury. Color echo
      Doppler and angio-computed tomography demonstrated a fusiform aneurysm of the
      zygomatic orbital artery, a branch of the superficial temporal artery. Blood
      tests were negative for human immunodeficiency virus (HIV), hepatitis C (HCV),
      and hepatitis B (HBV) markers. Aneurysmectomy under local anesthesia was
      performed. Histology of the surgical specimen confirmed the diagnosis of a true
      aneurysm measuring 8.4 * 5.7 mm, which showed no atherosclerotic degeneration of
      the vessel walls; the lumen was filled by a recent thrombus but without
      inflammatory cells. Surgical treatment is indicated for the prevention of
      rupture, the relief of pain when present, and the removal of facial defects. To
      the authors' knowledge, this is the first case in the literature of a true
      aneurysm of the zygomatic orbital artery.

PMID- 22454651
TI  - Recurrent Urinary Tract Infections due to Asymptomatic Colonic Diverticulitis.
AB  - Colovesical fistula is a common complication of diverticulitis. Pneumaturia,
      fecaluria, urinary tract infections, abdominal pain, and dysuria are commonly
      reported. The authors report a case of colovesical fistula due to asymptomatic
      diverticulitis, and they emphasize the importance of deeply investigate recurrent
      urinary tract infection without any bowel symptoms. They also briefly review the
      literature.

PMID- 22454652
TI  - Validation of the Antiproliferative Effects of Organic Extracts from the Green
      Husk of Juglans regia L. on PC-3 Human Prostate Cancer Cells by Assessment of
      Apoptosis-Related Genes.
AB  - With the increased use of plant-based cancer chemotherapy, exploring the
      antiproliferative effects of phytochemicals for anticancer drug design has gained
      considerable attention worldwide. This study was undertaken to investigate the
      effect of walnut green husk extracts on cell proliferation and to determine the
      possible molecular mechanism of extract-induced cell death by quantifying the
      expression of Bcl-2, Bax, caspases-3, and Tp53. PC-3 human prostate cancer cells.
      In this study, we found that green husk extracts suppressed proliferation and
      induced apoptosis in a dose- and time-dependent manner by modulating expression
      of apoptosis-related genes. This involved DNA fragmentation (determined by TUNEL
      assay) and significant changes in levels of mRNA and the expression of
      corresponding proteins. An increase in expressions of Bax, caspase-3, and tp53
      genes and their corresponding proteins was detected using real-time PCR and
      western blot analysis in PC-3 cells treated with the green husk organic extracts.
      In contrast, Bcl2 expression was downregulated after exposure to the extracts.
      Our data suggest the presence of bioactive compound(s) in walnut green husks that
      are capable of killing prostate carcinoma cells by inducing apoptosis and that
      the husks are a candidate source of anticancer drugs.

PMID- 22454653
TI  - Potent Antifungal Activity of Pure Compounds from Traditional Chinese Medicine
      Extracts against Six Oral Candida Species and the Synergy with Fluconazole
      against Azole-Resistant Candida albicans.
AB  - This study was designed to evaluate the in vitro antifungal activities of four
      traditional Chinese medicine (TCM) extracts. The inhibitory effects of
      pseudolaric acid B, gentiopicrin, rhein, and alion were assessed using standard
      disk diffusion and broth microdilution assays. They were tested against six oral
      Candida species, Candida albicans, Candida glabrata, Candida tropicalis, Candida
      krusei, Candida dubliniensis, and Candida guilliermondii, including clinical
      isolates from HIV-negative, HIV-positive, and Sjogren's syndrome patients. It was
      found that pseudolaric acid B had the most potent antifungal effect and showed
      similar antifungal activity to all six Candida spp, and to isolates from HIV
      negative, HIV-positive, and Sjogren's syndrome patients. The MIC values ranged
      from 16 to 128 MUg/mL. More interestingly, a synergistic effect of pseudolaric
      acid B in combination with fluconazole was observed. We suggest that pseudolaric
      acid B might be a potential therapeutic fungicidal agent in treating oral
      candidiasis.

PMID- 22454654
TI  - Inhibitory Effect of Nelumbo nucifera (Gaertn.) on the Development of Atopic
      Dermatitis-Like Skin Lesions in NC/Nga Mice.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease which has a complex
      etiology that encompasses immunologic responses. The study was carried out to
      examine the effect of Nelumbo nucifera (Gaertn.) leaf (NL) on the AD-like skin
      lesion induced by repeated epicutaneous application of 2,4-dinitrochlorobenzene
      (DNCB) on the dorsal skin of NC/Nga mice. Three different doses of NL (5, 25, and
      50 mg/mice/day) were administered orally from the day of sensitization with DNCB
      for 4 weeks. The efficacy of NL was judged by histopathological examination,
      blood IgE level, measurement of transepidermal water loss (TEWL), scratching
      behavior, and skin severity score. NL resulted in the suppression of clinical
      severity score, TEWL, scratching behavior, and blood IgE level. Histopathologic
      analyses revealed that thickening of the epidermis and mast cell degranulation
      was significantly reduced in NL group. These results suggest that NL may be a
      useful natural resource for the management of AD.

PMID- 22454655
TI  - Traditional chinese herbal patch for short-term management of knee
      osteoarthritis: a randomized, double-blind, placebo-controlled trial.
AB  - Objective. To assess the short-term efficacy and safety of two kinds of
      Traditional Chinese herbal patches, Fufang Nanxing Zhitong Gao (FNZG) and
      Shangshi Jietong Gao (SJG), for painful knee osteoarthritis (OA). Methods.
      Patients were randomly enrolled in a double-blind, placebo-controlled study to
      receive FNZG (n = 60), SJG (n = 60), or placebo patch (n = 30) for 7 days.
      Outcome measures included visual analogue scale (VAS), Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese
      Medicine Syndrome Questionnaire (TCMSQ) subscale. Results. Although there was no
      significant difference among, three groups in short-term pain management,
      patients receiving FNZG got significant improvement in symptom of fear of
      coldness as compared with placebo patch (P = 0.029). The most common local
      adverse events of rash, itching, erythema, and slightly damaged skin were
      observed in 7% of participants. Conclusions. FNZG may be a useful treatment for
      symptom of knee OA and merits long-term study in broader populations.

PMID- 22454656
TI  - Chinese herb and formulas for promoting blood circulation and removing blood
      stasis and antiplatelet therapies.
AB  - Atherothrombosis, which directly threatens people's health and lives, is the main
      cause of morbidity and mortality all over the world. Platelets play a key role in
      the development of acute coronary syndromes (ACSs) and contribute to
      cardiovascular events. Oral antiplatelet drugs are a milestone in the therapy of
      cardiovascular atherothrombotic diseases. In recent years, many reports have
      shown the possibility that "resistance" to oral anti-platelet drugs and many
      adverse reactions, such as serious bleeding risk, which provides an impetus for
      developing new anti-platelet drugs possesses highly efficiency and fewer adverse
      effects. Study on the blood stasis syndrome and promoting blood circulation and
      removing blood stasis is the most active field of research of integration of
      traditional and western medicine in China. Blood-stasis syndrome and platelet
      activation have close relationship, many Chinese herb and formulas for promoting
      blood circulation and removing blood stasis possess definite anti-platelet
      effect. This paper covers the progress of anti-platelet mechanism of Chinese herb
      and formulas for promoting blood circulation and removing blood stasis and is to
      be deeply discussed in further research.

PMID- 22454657
TI  - Antioxidant activities and phytochemical study of leaf extracts from 18
      indigenous tree species in taiwan.
AB  - The objective of this study is to assess antioxidant activities of methanolic
      extracts from the leaves of 18 indigenous tree species in Taiwan. Results
      revealed that, among 18 species, Acer oliverianum exhibited the best free radical
      scavenging activities. The IC(50) values were 5.8 and 11.8 MUg/mL on DPPH radical
      and superoxide radical scavenging activities, respectively. In addition, A.
      oliverianum also exhibited the strongest ferrous ion chelating activity. Based on
      a bioactivity-guided isolation principle, the resulting methanolic crude extracts
      of A. oliverianum leaves were fractionated to yield soluble fractions of hexane,
      EtOAc, BuOH, and water. Of these, the EtOAc fraction had the best antioxidant
      activity. Furthermore, 8 specific phytochemicals were isolated and identified
      from the EtOAc fraction. Among them, 1,2,3,4,6-O-penta-galloyl-beta-D
      glucopyranose had the best free radical scavenging activity. These results
      demonstrate that methanolic extracts and their derived phytochemicals of A.
      oliverianum leaves have excellent antioxidant activities and thus they have great
      potential as sources for natural health products.

PMID- 22454658
TI  - Effect of toki-shakuyaku-san on regional cerebral blood flow in patients with
      mild cognitive impairment and Alzheimer's disease.
AB  - The aim of this study was to examine the effect of toki-shakuyaku-san (TSS) on
      mild cognitive impairment (MCI) and Alzheimer's disease (AD) using single-photon
      emission computed tomography (SPECT). All subjects were administered TSS (7.5
      g/day) for eight weeks. SPECT and evaluations using the Mini Mental State
      Examination (MMSE), Neuropsychiatric Inventory, and Physical Self-Maintenance
      Scale were performed before and after treatment with TSS. Three patients with MCI
      and five patients with AD completed the study. No adverse events occurred during
      the study period. After treatment with TSS, regional cerebral blood flow (rCBF)
      in the posterior cingulate was significantly higher than that before treatment.
      No brain region showed a significant decrease in rCBF. TSS treatment also tended
      to improve the score for orientation to place on the MMSE. These results suggest
      that TSS could be useful for treatment of MCI and AD.

PMID- 22454659
TI  - Systematic Review of Chinese Herbal Medicines for Preventing in-Stent Coronary
      Restenosis after Percutaneous Coronary Intervention.
AB  - Percutaneous coronary intervention (PCI) with stent placement is a standard
      treatment for coronary artery disease (CAD). In-stent restenosis after PCI
      remains a challenging clinical problem. In China, Chinese herbal medicines (CHMs)
      are widely used for preventing restenosis. This paper systematically reviewed the
      literature on the effectiveness and safety of CHMs in preventing restenosis after
      PCI in patients with CAD. Electronic databases were searched for randomized
      controlled trials that compared CHMs plus RWM with the same RWM plus placebo in
      preventing restenosis after PCI. A total of 52 trials (4905 patients) on 34 CHMs
      met the inclusion criteria and were analyzed. Ten trials had low risk of bias.
      Methodological quality of included trials was generally poor. Meta-analysis
      showed that at the end of at least 3 months' followup, CHMs plus RWM could
      significantly reduce restenosis rate, cardiac mortality, recurrence rate of
      angina, acute myocardial infarction, numbers of repeat PCI, and numbers of
      coronary artery bypass graft. Reported adverse events included gastrointestinal
      upset, granulocytopenia, and increased alanine transaminase (ALT). CHMs may help
      prevent restenosis, thus reducing cardiac mortality after PCI. Caution should be
      exercised in drawing a definitive conclusion due to the poor methodological
      quality of the trials reviewed.

PMID- 22454660
TI  - Electroacupuncture suppresses discrete cue-evoked heroin-seeking and fos protein
      expression in the nucleus accumbens core in rats.
AB  - Relapse to drug seeking was studied using a rodent model of reinstatement induced
      by exposure to drug-related cues. Here, we used intravenous drug self
      administration procedures in rats to further investigate the beneficial effects
      of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of
      relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily
      for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent
      from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14
      days during heroin abstinence. We tested these animals for contextual and
      discrete cue-induced reinstatement of active responses. We also applied
      immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens
      (NACc) core and shell after reinstatement test. We found that active responses
      elicited by both contextual cues and discrete cues were high in the rats trained
      with heroin than in saline controls. EA treatment significantly reduced active
      responses elicited by discrete cues. EA stimulation attenuated Fos expression in
      the core but not the shell of the NACc. Altogether, these results highlight the
      therapeutic benefit of EA in preventing relapse to drug addiction.

PMID- 22454661
TI  - Ethanol extracts of fruiting bodies of Antrodia cinnamomea suppress CL1-5 human
      lung adenocarcinoma cells migration by inhibiting matrix metalloproteinase-2/9
      through ERK, JNK, p38, and PI3K/Akt signaling pathways.
AB  - Metastatic cancer attributes to a major cause of cancer death. In this pioneer
      study, we aimed to investigate how Antrodia cinnamomea (A. cinnamomea),
      indigenous to Taiwan, affects migration ability of highly metastatic human
      adenocarcinoma lung cancer cells CL1-5. Our result demonstrated that noncytotoxic
      ethanol extract of fruiting bodies of A. cinnamomea (EEAC) exhibited a dose
      dependent inhibitory effect on motility and migration of the highly metastatic
      CL1-5 cells. Results of a gelatin zymography assay illustrated that A. cinnamomea
      repressed the activities of matrix metalloproteinase- (MMP-) 2 and 9 in a dose
      dependent manner. A. cinnamomea administration decreased MMP-9 and MMP-2 protein
      expressions from Western blotting assay, whereas the expression of the tissue
      inhibitors of MMP (TIMP-1 and TIMP-2) increased. Additional study disclosed that
      A. cinnamomea suppressed FAK, ERK1/2, p38, AKT, and JNK1/2 phosphorylation, and
      also PI3K and Rac-1 were found decreased. Further, treatment of CL1-5 cells with
      inhibitors specific for PI3K (LY294002), ERK1/2 (PD98059), JNK (SP600125), and
      p38 MAPK (SB203580) decreased the expression of MMP-2 and MMP-9. Taken together,
      EEAC induced FAK phosphorylation and exhibited its antimigration activities via
      the PI3K/AKT and MAPK signalings in CL1-5 cells. This is the pioneer study
      verifying the antimigration activity of A. cinnamomea against human lung
      adenocarcinoma CL1-5 cancer cells [corrected].

PMID- 22454662
TI  - Demethoxycurcumin Retards Cell Growth and Induces Apoptosis in Human Brain
      Malignant Glioma GBM 8401 Cells.
AB  - Demethoxycurcumin (DMC; a curcumin-related demethoxy compound) has been recently
      shown to display antioxidant and antitumor activities. It has also produced a
      potent chemopreventive action against cancer. In the present study, the
      antiproliferation (using the MTT assay, DMC was found to have cytotoxic
      activities against GBM 8401 cell with IC(50) values at 22.71 MUM) and induced
      apoptosis effects of DMC have been investigated in human brain malignant glioma
      GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP), DNA
      fragmentation, caspase activation, and NF-kappaB transcriptional factor activity.
      By these approaches, our results indicated that DMC has produced an inhibition of
      cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both
      effects were observed to increase in proportion with the dosage of DMC treatment,
      and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401
      cells via mitochondria- and caspase-dependent pathways.

PMID- 22454663
TI  - Aqueous Extract of Paeonia suffruticosa Inhibits Migration and Metastasis of
      Renal Cell Carcinoma Cells via Suppressing VEGFR-3 Pathway.
AB  - Renal cell carcinoma (RCC) cells are characterized by strong drug resistance and
      high metastatic incidence. In this study, the effects of ten kinds of Chinese
      herbs on RCC cell migration and proliferation were examined. Aqueous extract of
      Paeonia suffruticosa (PS-A) exerted strong inhibitory effects on cancer cell
      migration, mobility, and invasion. The results of mouse xenograft experiments
      showed that the treatment of PS-A significantly suppressed tumor growth and
      pulmonary metastasis. We further found that PS-A markedly decreased expression of
      VEGF receptor-3 (VEGFR-3) and phosphorylation of FAK in RCC cells. Moreover, the
      activation of Rac-1, a modulator of cytoskeletal dynamics, was remarkably reduced
      by PS-A. Additionally, PS-A suppressed polymerization of actin filament as
      demonstrated by confocal microscopy analysis and decreased the ratio of F-actin
      to G-actin in RCC cells, suggesting that PS-A inhibits RCC cell migration through
      modulating VEGFR-3/FAK/Rac-1 pathway to disrupt actin filament polymerization. In
      conclusion, this research elucidates the effects and molecular mechanism for
      antimigration of PS-A on RCC cells and suggests PS-A to be a therapeutic or
      adjuvant strategy for the patients with aggressive RCC.

PMID- 22454664
TI  - In Vitro Assessment of Cytochrome P450 2C19 Potential of Naoxintong.
AB  - The effects of Buchang Naoxintong Capsules (BNCs) on S-mephenytoin 4'
      hydroxylation activities in human liver microsomes in vitro were assessed. Human
      liver microsome was prepared by different ultracentrifugation. Human liver
      microsome incubation experiment was carried out to assay BNC on S-mephenytoin 4'
      hydroxylation activities. The 4'-hydroxylation of S-mephenytoin, a representative
      substrate toward CYP2C19, was increased by phenytoin sodium (positive control).
      After the incubation, the metabolites of the substrates (4'-OH-mephenytoin) were
      determined by HPLC. Results showed that both phenytoin sodium and BNC showed
      obvious increase effect on CYP2C19. The enzymatic reaction of BNC was observed
      with concentrations ranging from 5 MUg/mL to 250 MUg/mL. Compared to blank, the
      increase effect of BNC showed significant difference from the beginning of
      concentration of 150 MUg/mL (P < 0.001). The conclusion was that BNC showed
      obvious increase effect on the catalytic activities of drug-metabolising CYP2C19
      enzyme.

PMID- 22454666
TI  - Chemical Analysis and Study of Phenolics, Antioxidant Activity, and Antibacterial
      Effect of the Wood and Bark of Maclura tinctoria (L.) D. Don ex Steud.
AB  - Maclura tinctoria (L.) D. Don ex Steud. has one of the highest qualities among
      the coefficients for Brazilian woods (up to 9.6) and resistance rates equivalent
      to Indian teak (Tectona grandis). In this study, the macromolecular constituents
      and total phenols compounds as well as the antioxidant and antibacterial
      activities of this wood were evaluated. Total phenols and proanthocyanidin levels
      were higher in wood when compared with bark levels. The antioxidant activity of
      wood extracts (IC(50) = 18.7 MUg/mL) was more effective than that of bark
      extracts (IC(50) = 20.9 MUg/mL). Wood and bark extracts revealed a high potential
      for inhibition of aerobic and anaerobic bacteria. The bark extracts were the most
      active (MIC from 20 to 60 MUg/mL). Both antioxidant activity and high potential
      for bacteria inhibition turn these extracts promising for drug formulations,
      especially as antibacterial agent.

PMID- 22454665
TI  - Hematopoietic cell transplant and use of massage for improved symptom management:
      results from a pilot randomized control trial.
AB  - Background. Pediatric hematopoietic cell transplant (HCT) is a lifesaving
      treatment that often results in physical and psychological discomfort. An
      acupressure-massage intervention may improve symptom management in this setting.
      Methods. This randomized controlled pilot trial compared a combined massage
      acupressure intervention to usual care. Children were offered three practitioner
      provided sessions per week throughout hospitalization. Parents were trained to
      provide additional acupressure as needed. Symptoms were assessed using nurses'
      reports and two questionnaires, the behavioral affective and somatic experiences
      scale and the Peds quality of life cancer module. Results. We enrolled 23
      children, ages 5 to 18. Children receiving the intervention reported fewer days
      of mucositis (Hedges' g effect size ES = 0.63), lower overall symptom burden (ES
      = 0.26), feeling less tired and run-down (ES = 0.86), having fewer
      moderate/severe symptoms of pain, nausea, and fatigue (ES = 0.62), and less pain
      (ES = 0.42). The intervention group showed trends toward increasing
      contentness/serenity (ES = +0.50) and decreasing depression (ES = -0.45), but not
      decreased anxiety (ES = +0.42). Differences were not statistically significant.
      Discussion. Feasibility of studying massage-acupressure was established in
      children undergoing HCT. Larger studies are needed to test the efficacy of such
      interventions in reducing HCT-associated symptoms in children.

PMID- 22454667
TI  - Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses
      Ovalbumin-Induced Airway Hyperresponsiveness without Influencing
      Xylazine/Ketamine-Induced Anesthesia.
AB  - Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the
      traditional Chinese medicine, "Chen Pi." Therefore, we were interested in
      investigating its effects on ovalbumin- (OVA-) induced airway
      hyperresponsiveness, and clarifying its rationale for ameliorating asthma and
      chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a
      therapeutic (PDE4(H)/PDE4(L)) ratio of >11. Hesperetin (10 ~ 30 MUmol/kg,
      intraperitoneally (i.p.)) dose-dependently and significantly attenuated the
      airway hyperresponsiveness induced by methacholine. It also significantly
      suppressed the increases in total inflammatory cells, macrophages, lymphocytes,
      neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)
      2, IL-4, IL-5, interferon-gamma, and tumor necrosis factor-alpha in
      bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly
      suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum.
      However, hesperetin did not influence xylazine/ketamine-induced anesthesia,
      suggesting that hesperetin has few or no emetic effects. In conclusion, the
      rationales for ameliorating allergic asthma and COPD by hesperetin are anti
      inflammation, immunoregulation, and bronchodilation.

PMID- 22454668
TI  - Ichthyofauna used in traditional medicine in Brazil.
AB  - Fish represent the group of vertebrates with the largest number of species and
      the largest geographic distribution; they are also used in different ways by
      modern civilizations. The goal of this study was to compile the current knowledge
      on the use of ichthyofauna in zootherapeutic practices in Brazil, including
      ecological and conservational commentary on the species recorded. We recorded a
      total of 85 species (44 fresh-water species and 41 salt-water species) used for
      medicinal purposes in Brazil. The three most commonly cited species were Hoplias
      malabaricus, Hippocampus reidi, and Electrophorus electricus. In terms of
      conservation status, 65% of species are in the "not evaluated" category, and 14%
      are in the "insufficient data" category. Three species are in the "vulnerable"
      category: Atlantoraja cyclophora, Balistes vetula, and Hippocampus erectus.
      Currently, we cannot avoid considering human pressure on the population dynamics
      of these species, which is an essential variable for the conservation of the
      species and the ecosystems in which they live and for the perpetuation of
      traditional medical practices.

PMID- 22454669
TI  - Effects of Electroacupuncture on N-Methyl-D-aspartate Receptor-Related Signaling
      Pathway in the Spinal Cord of Normal Rats.
AB  - This study examined the influence of the N-methyl-D-aspartate receptor (NMDAR) on
      the modulation of related spinal signaling after electroacupuncture (EA)
      treatment in normal rats. Bilateral 2 Hz EA stimulations (1-2-3.0 mA) were
      delivered at acupoints corresponding to Zusanli (ST36) and Sanyinjiao (SP6) in
      men for 30 min. Thermal sensitization was strongly inhibited by EA, but this
      analgesia was reduced by preintrathecal injection of the NMDAR antagonist, MK801.
      Phosphorylation of the NMDAR NR2B subunit, cAMP response element-binding protein
      (CREB), and especially phosphatidylinositol 3-kinase (PI3K) were significantly
      induced by EA. However, these marked phosphorylations were not observed in MK801
      pretreated rats. EA analgesia was reduced by preintrathecal injection with the
      calcium chelators Quin2 and TMB8, similar to the results evident using MK801.
      Phosphorylation of PI3K and CREB induced by EA was also inhibited by TMB8.
      Calcium influx by NMDAR activation may play an important role in EA analgesia of
      normal rats through the modulation of the phosphorylation of spinal PI3K and
      CREB.

PMID- 22454670
TI  - Antiprotozoal and Antimycobacterial Activities of Pure Compounds from
      Aristolochia elegans Rhizomes.
AB  - We analyzed the antimycobacterial activity of the hexane extract of rhizomes from
      Aristolochia elegans. Some compounds of this extract were purified and tested
      against a group of drug-resistant Mycobacterium tuberculosis strains. We also
      evaluated their antiprotozoal activities. The hexane extract was active against
      M. tuberculosis H37Rv at a MIC = 100 MUg mL(-1); the pure compounds eupomatenoid
      1, fargesin, and (8R,8'R,9R)-cubebin were active against M. tuberculosis H37Rv
      (MIC = 50 MUg mL(-1)), while fargesin presented activity against three
      monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M.
      tuberculosis (MIC < 50 MUg mL(-1)). Both the extract and eupomatenoid-1 were very
      active against E. histolytica and G. lamblia (IC(50) < 0.624 MUg mL(-1)); in
      contrast, fargesin and (8R,8'R,9R)-cubebin were moderately active (IC(50) < 275
      MUg mL(-1)). In this context, two compounds responsible for the antimycobacterial
      presented by A. elegans are fargesin and cubebin, although others may exert this
      activity also. In addition to the antimycobacterial activity, the hexane extract
      has important activity against E. histolytica and G. lamblia, and eupomatenoid-1
      is one of the compounds responsible for the antiparasite activity.

PMID- 22454671
TI  - Ethnopharmacokinetic- and activity-guided isolation of a new antidepressive
      compound from fructus aurantii found in the traditional chinese medicine chaihu
      shugan-san: a new approach and its application.
AB  - Aims. We aimed to identify an antidepressive compound found in traditional
      Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and
      activity-guided isolation (EAGI). Methods. The new approach targets an unknown
      chromatographic peak produced by an absorbed compound found in oral Chaihu-Shugan
      San (CSS) taken by patients with depression. Once the compound was isolated from
      Fructus Aurantii (FA), spectral data was employed to identify the compound. The
      effects of this compound, FA, and CSS on depressive behaviors were investigated.
      Results. The identified compound was merazin hydrate (MH) according to the new
      approach. MH, FA, and CSS significantly reduced immobility time and increased
      locomotor activity. The effects of MH, FA and CSS were similar to Fluoxetine at
      high doses. Conclusion. MH, a compound whose antidepressive effect is similar to
      FA and CSS, was isolated for the first time from FA via targeting its
      corresponding unknown chromatographic peak, and its antidepressive effect was
      compared with FA or CSS. These findings highlight the potential for drug R&D and
      pharmacological research of ~100,000 TCMs.

PMID- 22454673
TI  - Prevalence of Metabolic Syndrome according to Sasang Constitutional Medicine in
      Korean Subjects.
AB  - Metabolic syndrome (MS) is a complex disorder defined by a cluster of abdominal
      obesity, atherogenic dyslipidemia, hyperglycemia, and hypertension; the condition
      is recognized as a risk factor for diabetes and cardiovascular disease. This
      study assessed the effects of the Sasang constitution group (SCG) on the risk of
      MS in Korean subjects. We have analyzed 1,617 outpatients of Korean oriental
      medicine hospitals who were classified into three SCGs, So-Yang, So-Eum, and Tae
      Eum. Significant differences were noted in the prevalence of MS and the
      frequencies of all MS risk factors among the three SCGs. The odds ratios for MS
      as determined via multiple logistic regression analysis were 2.004 for So-Yang
      and 4.521 for Tae-Eum compared with So-Eum. These results indicate that SCG may
      function as a significant risk factor of MS; comprehensive knowledge of Sasang
      constitutional medicine may prove helpful in predicting susceptibility and
      developing preventive care techniques for MS.

PMID- 22454672
TI  - An Innovative High-Tech Acupuncture Product: SXDZ-100 Nerve Muscle Stimulator,
      Its Theoretical Basis, Design, and Application.
AB  - We introduce the theoretical basis, design, and application of a patented
      innovative high-tech product, SXDZ-100 nerve and muscle stimulator. This product
      is featured with a built-in chip containing transcoding information from
      different acupuncture manipulation collected from the wide dynamic neurons (WDR)
      in the spinal dorsal horn in animal experiments, which is bioinformation feedback
      therapy. The discharges of WDR neurons excited by different manipulations are
      analyzed using chaos theory in this study. It combines the advantages of manual
      acupuncture (MA) like no receptor adaptation and treatment individualization and
      that of electroacupuncture (EA) such as relatively low stimulation intensity and
      good quantification and thus makes it more effective than common stimulators in
      acupuncture clinic.

PMID- 22454674
TI  - Cytotoxic and Antifungal Activities of 5-Hydroxyramulosin, a Compound Produced by
      an Endophytic Fungus Isolated from Cinnamomum mollisimum.
AB  - An endophytic fungus isolated from the plant Cinnamomum mollissimum was
      investigated for the bioactivity of its metabolites. The fungus, similar to a
      Phoma sp., was cultured in potato dextrose broth for two weeks, followed by
      extraction with ethyl acetate. The crude extract obtained was fractionated by
      high-performance liquid chromatography. Both crude extract and fractions were
      assayed for cytotoxicity against P388 murine leukemic cells and inhibition of
      bacterial and fungal pathogens. The bioactive extract fraction was purified
      further and characterized by nuclear magnetic resonance, mass spectral and X-ray
      crystallography analysis. A polyketide compound, 5-hydroxyramulosin, was
      identified as the constituent of the bioactive fungal extract fraction. This
      compound inhibited the fungal pathogen Aspergillus niger (IC(50) 1.56 MUg/mL) and
      was cytotoxic against murine leukemia cells (IC(50) 2.10 MUg/mL). 5
      Hydroxyramulosin was the major compound produced by the endophytic fungus. This
      research suggests that fungal endophytes are a good source of bioactive
      metabolites which have potential applications in medicine.

PMID- 22454675
TI  - The Antiproliferative Activity of Sclerotia of Lignosus rhinocerus (Tiger Milk
      Mushroom).
AB  - Lignosus rhinocerus, the tiger milk mushroom, is one of the most important
      medicinal mushrooms used by the indigenous people of Southeast Asia and China. It
      has been used to treat breast cancer. A cold water extract (LR-CW) prepared from
      the sclerotia of L. rhinocerus cultivar was found to exhibit antiproliferative
      activity against human breast carcinoma (MCF-7) and human lung carcinoma (A549),
      with IC(50) of 96.7 MUg/mL and 466.7 MUg/mL, respectively. In comparison, LR-CW
      did not show significant cytotoxicity against the two corresponding human normal
      cells, 184B5 (human breast cell) and NL 20 (human lung cell). DNA fragmentation
      studies suggested that the cytotoxic action of LR-CW against cancer cells is
      mediated by apoptosis. Sephadex G-50 gel filtration fractionation of LR-CW
      yielded a high-molecular-weight and a low-molecular-weight fraction. The high
      molecular-weight fraction contains mainly carbohydrate (68.7%) and small amount
      of protein (3.6%), whereas the low-molecular-weight fraction contains 31%
      carbohydrate and was devoid of protein. Only the high-molecular-weight fraction
      exhibited antiproliferative activity against cancer cells, with IC(50) of 70.0
      MUg/mL and 76.7 MUg/mL, respectively. Thus, the cytotoxic action of the LR-CW is
      due to the high-molecular-weight fraction, either the proteins or protein
      carbohydrate complex.

PMID- 22454676
TI  - Kappa-opioid receptors in the caudal nucleus tractus solitarius mediate 100 hz
      electroacupuncture-induced sleep activities in rats.
AB  - Previous results demonstrated that 10 Hz electroacupuncture (EA) of Anmian
      acupoints in rats during the dark period enhances slow wave sleep (SWS), which
      involves the induction of cholinergic activity in the caudal nucleus tractus
      solitarius (NTS) and subsequent activation of opioidergic neurons and MU
      receptors. Studies have shown that different kinds of endogenous opiate peptides
      and receptors may mediate the consequences of EA with different frequencies.
      Herein, we further elucidated that high-frequency (100 Hz)-EA of Anmian enhanced
      SWS during the dark period but exhibited no direct effect on rapid eye movement
      (REM) sleep. High-frequency EA-induced SWS enhancement was dose-dependently
      blocked by microinjection of naloxone or kappa-receptor antagonist (nor
      binaltorphimine) into the caudal NTS, but was affected neither by MU-
      (naloxonazine) nor delta-receptor antagonists (natatrindole), suggesting the role
      of NTS kappa-receptors in the high-frequency EA-induced SWS enhancement. Current
      and previous results depict the opioid mechanisms of EA-induced sleep.

PMID- 22454677
TI  - Tanshinone IIA: A Promising Natural Cardioprotective Agent.
AB  - Tanshinone IIA (Tan IIA) is a member of the major lipophilic components extracted
      from the root of Salvia miltiorrhiza Bunge, which is currently used in China and
      other neighboring countries to treat patients suffering from myocardial
      infarction (MI), angina pectoris, stroke, diabetes, sepsis, and other conditions.
      However, Tan IIA is not easy to be absorbed through intestinal pathway. To raise
      the bioavailability of the herb, sodium tanshinone IIA sulfonate (STS) was
      developed. This paper discussed the pharmacology of Tan IIA, STS, and their
      potential cardioprotective effects.

PMID- 22454678
TI  - Zuonin B Inhibits Lipopolysaccharide-Induced Inflammation via Downregulation of
      the ERK1/2 and JNK Pathways in RAW264.7 Macrophages.
AB  - We investigated whether Zuonin B exerts immunological effects on RAW264.7 cells.
      Zuonin B, isolated from flower buds of Daphne genkwa, suppressed the levels of
      nitric oxide and prostaglandin E(2), as well as proinflammatory cytokines, such
      as tumor necrosis factor-alpha and interleukin-(IL-) 6, in lipopolysaccharide
      stimulated macrophages. Moreover, the compound inhibited cyclooxygenase-2 and
      inducible nitric oxide synthase expression. Zuonin B attenuated NF-kappaB (NF
      kappaB) activation via suppressing proteolysis of inhibitor kappa B-alpha
      (IkappaB-alpha) and p65 nuclear translocation as well as phosphorylation of
      extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase.
      Additionally, IL-4 and IL-13 production in ConA-induced splenocytes was inhibited
      by Zuonin B. In conclusion, the anti-inflammatory effects of Zuonin B are
      attributable to the suppression of proinflammatory cytokines and mediators via
      blockage of NF-kappaB and AP-1 activation. Based on these findings, we propose
      that Zuonin B is potentially an effective functional chemical candidate for the
      prevention of inflammatory diseases.

PMID- 22454679
TI  - Reliability and External Validity of AMSTAR in Assessing Quality of TCM
      Systematic Reviews.
AB  - Objective. The aim of this study is to measure the reliability and external
      validity of AMSTAR by applying it to a sample of TCM systematic reviews. Study
      Design and Methods. We tested the agreement, reliability, construct validity, and
      feasibility of AMSTAR through comparisons with OQAQ. Statistical analyses were
      performed by using SPSS 13.0. Results. A random of sample with 41 TCM systematic
      reviews was selected from a database. The interrater agreement of the individual
      items of AMSTAR was moderate with a mean kappa of 0.50 (95% CI: 0.26, 0.73). The
      ICC for AMSTAR against OQAQ (total score of 9 items, excluding item 10) was 0.87
      (95% CI: 0.76, 0.93). Conclusions. Although there is room for improvement on few
      items, the new tool is reliable, valid, and easy to use for methodological
      quality assessment of systematic reviews on TCM.

PMID- 22454680
TI  - Effect of human placental extract on health status in elderly koreans.
AB  - Objectives. Human placental extract (HPE) has begun to be used in Korea in
      various ways to improve health, even though evidence-based data is insufficient.
      This study investigated the effects of HPE on health status in elderly Koreans.
      Design. Randomized, single-blind, and case-control study design. Setting and
      Participants. Thirty-nine community-dwelling healthy Koreans >=65 years of age.
      Intervention. The participants were randomly categorized into a placebo group (n
      = 17) and HPE group (n = 22). The HPE group received abdominal subcutaneous
      injections of HPE for 8 weeks. The placebo group was injected with normal saline.
      Measurements. The degree of health status was surveyed by the Korean health
      status measure for the elderly (KoHSME V1.0) at baseline and the end of the
      study. Results. In the HPE group, the scores of physical function, sexual life,
      and general heath perception at the end of the study period were significantly
      improved from baseline (P = .007, .020, and .005, resp.), while the health status
      of the placebo group remained unchanged during the study period. There was a
      significant difference over the study period between the two groups in the mean
      change of the physical function score (P = .036). Conclusion. A HPE injection
      regimen can improve the health status in elderly Koreans.

PMID- 22454681
TI  - Effects of Brugmansia arborea Extract and Its Secondary Metabolites on Morphine
      Tolerance and Dependence in Mice.
AB  - The aim of the present study was to investigate, in vivo, the effect of a
      Brugmansia arborea extract (BRU), chromatographic fractions (FA and FNA), and
      isolated alkaloids on the expression and the acquisition of morphine tolerance
      and dependence. Substances were acutely (for expression) or repeatedly (for
      acquisition) administered in mice treated with morphine twice daily for 5 or 6
      days, in order to make them tolerant or dependent. Morphine tolerance was
      assessed using the tail-flick test at 1st and 5th days. Morphine dependence was
      evaluated through the manifestation of withdrawal symptoms induced by naloxone
      injection at 6th day. Results showed that BRU significantly reduced the
      expression of morphine tolerance, while it was ineffective to modulate its
      acquisition. Chromatographic fractions and pure alkaloids failed to reduce
      morphine tolerance. Conversely BRU, FA, and pure alkaloids administrations
      significantly attenuated both development and expression of morphine dependence.
      These data suggest that Brugmansia arborea Lagerh might have human therapeutic
      potential for treatment of opioid addiction.

PMID- 22454682
TI  - Angelicae Dahuricae Radix Inhibits Dust Mite Extract-Induced Atopic Dermatitis
      Like Skin Lesions in NC/Nga Mice.
AB  - We examined whether Angelicae Dahuricae Radix (AR) suppresses the development of
      atopic dermatitis (AD)-like skin lesions induced by Dermatophagoides farinae in
      NC/Nga mice. To investigate the effect of AR, we measured the AD severity score,
      measured plasma levels of IgE and histamine, and performed histological analysis
      in NC/Nga mice. We also confirmed the anti-inflammatory effects of AR by
      measuring TARC/CCL17 production from LPS-treated RAW 264.7 cells and mRNA levels
      of TARC and MDC/CCL22 in TNF-alpha/IFN-gamma-treated HaCaT cells. 10 mg/day of AR
      extract was applied for 4 weeks to NC/Nga mice. Both the AR extract and 0.1%
      tacrolimus suppressed the development of AD-like skin lesions and reduced
      dermatitis scores of the back and ear skin. AR extracts caused an inhibition of
      histological changes induced by repeated application of D. farinae and a
      reduction of IgE and histamine levels in plasma (P < 0.05). Furthermore, NO
      production in LPS-treated RAW 264.7 cells was diminished in a dose-dependent
      manner, and hTARC production and TARC and MDC mRNA levels in TNF-alpha/IFN-gamma
      treated HaCaT cells were diminished by AR. The inhibitory effect of AR on NO,
      TARC and MDC production may be associated with the suppression of AD-like skin
      lesions in D. farinae-induced NC/Nga mice.

PMID- 22454683
TI  - Effectiveness of the Novel Herbal Medicine, KIOM-MA, and Its Bioconversion
      Product, KIOM-MA128, on the Treatment of Atopic Dermatitis.
AB  - This study was conducted to determine if oral administration of the novel herbal
      medicine, KIOM-MA, and its Lactobacillus acidophilus-fermented product, KIOM
      MA128, has therapeutic properties for the treatment of atopic dermatitis (AD).
      Using AD-induced BALB/c mice by Ovalbumin and aluminum hydroxide, the
      effectiveness of KIOM-MA and KIOM-MA128 on AD was evaluated. Oral administration
      of KIOM-MA and KIOM-MA128 reduced major clinical signs of AD including
      erythema/darkening, edema/papulation, excoriations, lichenification/prurigo, and
      dryness. Interestingly, KIOM-MA128 more significantly improved AD-related
      symptoms including decrease of IgE level in the plasma as well as reduction of
      scratching behavior, skin severity in the AD BALB/c model. HPLC analysis showed
      the significant changes in the constituent patterns between KIOM-MA and KIOM
      MA128. Our results suggest that both KIOM-MA and KIOM-MA128 have potential for
      therapeutic reagent for the treatment of AD, and further, the efficacy is
      significantly enhanced by L. acidophilus fermentation via increases in its
      indicator molecule.

PMID- 22454684
TI  - Changes in cytokine expression after electroacupuncture in neuropathic rats.
AB  - The production of proinflammatory cytokines including interleukin-1 (IL-1),
      interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) plays a key
      role in chronic pain such as neuropathic pain. We investigated changes in
      cytokine expression in injured peripheral nerves and dorsal root ganglia (DRG)
      following electroacupuncture (EA) treatment. Neuropathic pain was induced by
      peripheral nerve injury to the left hind limb of Sprague-Dawley rats under
      pentobarbital anesthesia. Two weeks later, the nerve-injured rats were treated by
      EA for 10 minutes. The expression levels of IL-1beta, IL-6, and TNF-alpha in
      peripheral nerves and DRG of neuropathic rats were significantly increased in
      nerve-injured rats. However, after EA, the cytokine expression levels were
      noticeably decreased in peripheral nerves and DRG. These results suggest that EA
      stimulation can reduce the levels of proinflamtory cytokines elevated after nerve
      injury.

PMID- 22454685
TI  - Sino-European transcontinental basic and clinical high-tech acupuncture studies
      part 1: auricular acupuncture increases heart rate variability in anesthetized
      rats.
AB  - Evidence-based research concerning the effects of high-tech acupuncture on
      autonomic function was performed by two research teams from China and Austria.
      This study describes the first transcontinental teleacupuncture measurements in
      animals. Heart rate (HR) and heart rate variability (HRV) recordings in 10 male
      Sprague-Dawley anesthetized rats were performed under stable conditions in
      Beijing, China, and the data analysis was completed in Graz, Austria. The
      electrocardiograms (ECGs) were recorded by an HRV Medilog AR12 system during
      acupuncture of the ear and body (PC6 Neiguan, CV12 Zhongwan, ST36 Zusanli). The
      data were analyzed using specially adapted novel Austrian software. HR did not
      change significantly during any acupuncture stimulation in anesthetized rats (ear
      acupuncture, PC6, CV12, or ST36). Total HRV only changed significantly (P =
      0.025) during auricular acupuncture (acupoint heart). The low-frequency/high
      frequency ratio parameter decreased significantly (P = 0.03) during stimulation
      of ST36. This change was based on intensification of the related mechanism of
      blood pressure regulation that has been demonstrated in previous studies in
      humans. Modernization of acupuncture research performed as a collaboration
      between China and Austria has also been demonstrated.

PMID- 22454686
TI  - Topical Application of Chrysanthemum indicum L. Attenuates the Development of
      Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-gamma,
      and IL-4 in Nc/Nga Mice.
AB  - Chrysanthemum indicum L. (CIL) is widely used as an anti-inflammatory agent in
      Asia and our preliminary study revealed that CIL reduced interleukin (IL)-4 and
      IL-13 in 2,4-dinitrochlorobenzene (DNCB)-treated HaCaT cells, a human
      keratinocyte cell line. We investigated the atopic dermatitis (AD) effect of
      topically applied CIL in mice with AD-like symptoms. After topical application of
      1,3-butylen glycol (control), CIL-Low (5%), CIL-High (30%), or 0.1%
      hydrocortisone (HC) on the AD-like skin lesions in DNCB-treated NC/Nga mice for 5
      weeks, the ear thickness, mast cell infiltration, and serum immunoglobulin E
      (IgE), IgG1, IL-4 and interferon (IFN)-gamma were measured. The gene expressions
      of IL-4, IL-13, and IFN-gamma in the dorsal skin were assayed. CIL treatment
      dosedependently reduced severity of clinical symptoms of dorsal skin, ear
      thickness, and the number of mast cells and eosinophils. CIL-High significantly
      decreased serum IgE, IgG1, IL-4, and IFN-gamma levels and reduced mRNA levels of
      IFN-gamma, IL-4, and IL-13 in dorsal skin lesion. The improvement by CIL-High was
      similar to HC, but without its adverse effects such as skin atrophy maceration,
      and secondary infection. In conclusion, CIL may be an effective alternative
      substance for the management of AD.

PMID- 22454687
TI  - Anti-inflammatory and anticoagulative effects of paeonol on LPS-induced acute
      lung injury in rats.
AB  - Paeonol is an active component of Moutan Cortex Radicis and is widely used as an
      analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese
      medicine. We wanted to determine the role of paeonol in treating adult
      respiratory distress syndrome (ARDS). We established an acute lung injury (ALI)
      model in Sprague-Dawley rats, which was similar to ARDS in humans, using
      intratracheal administration of lipopolysaccharide (LPS). The intraperitoneal
      administration of paeonol successfully reduced histopathological scores and
      attenuated myeloperoxidase-reactive cells as an index of polymorphonuclear
      neutrophils infiltration and also reduces inducible nitric oxide synthase
      expression in the lung tissue, at 16 h after LPS administration. In addition,
      paeonol reduced proinflammatory cytokines in bronchoalveolar lavage fluid,
      including tumor-necrosis factor-alpha, interleukin-1beta, interleukin-6, and
      plasminogen-activated inhibition factor-1. These results indicated that paeonol
      successfully attenuates inflammatory and coagulation reactions to protect against
      ALI.

PMID- 22454688
TI  - Phyllanthus urinaria Induces Apoptosis in Human Osteosarcoma 143B Cells via
      Activation of Fas/FasL- and Mitochondria-Mediated Pathways.
AB  - Phyllanthus urinaria (P. urinaria), in this study, was used for the treatment of
      human osteosarcoma cells, which is one of the tough malignancies with few
      therapeutic modalities. Herein, we demonstrated that P. urinaria inhibited human
      osteosarcoma 143B cells growth through an apoptotic extrinsic pathway to activate
      Fas receptor/ligand expression. Both intracellular and mitochondrial reactive
      oxygen species were increased to lead to alterations of mitochondrial membrane
      permeability and Bcl-2 family including upregulation of Bid, tBid, and Bax and
      downregulation of Bcl-2. P. urinaria triggered an intrinsic pathway and amplified
      the caspase cascade to induce apoptosis of 143B cells. However, upregulation of
      both intracellular and mitochondrial reactive oxygen species and the sequential
      membrane potential change were less pronounced in the mitochondrial respiratory
      defective 143Brho(0) cells compared with the 143B cells. This study offers the
      evidence that mitochondria are essential for the anticancer mechanism induced by
      P. urinaria through both extrinsic and intrinsic pathways.

PMID- 22454690
TI  - Effect of Quercetin in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine
      Induced Mouse Model of Parkinson's Disease.
AB  - In this paper, the protective effect of the bioflavonoid quercetin on behaviors,
      antioxidases, and neurotransmitters in 1-methyl-4-phenyl-1, 2, 3, 6
      tetrahydropyridine-(MPTP-) induced Parkinson's disease (PD) was investigated.
      Quercetin treatment (50 mg/kg, 100 mg/kg and 200 mg/kg body weight) was orally
      administered for 14 consecutive days. The results show that quercetin treatment
      markedly improves the motor balance and coordination of MPTP-treated mice.
      Significant increases were observed in the activities of glutathione peroxidase
      (GPx), superoxide dismutase (SOD), and Na(+), K(+)-ATPase, AchE, the content of
      dopamine (DA) in the quercetin plus MPTP groups compared to those in the MPTP
      group. Significant reduction the 4-hydroxy-2-nonenal (4-HNE) immunoreactivity in
      striatum of brains was observed in the quercetin plus MPTP groups in comparison
      to the MPTP group. Taken together, we propose that quercetin has shown
      antiparkinsonian properties in our studies. More work is needed to explore
      detailed mechanisms of action.

PMID- 22454689
TI  - The effects of meditation on perceived stress and related indices of
      psychological status and sympathetic activation in persons with Alzheimer's
      disease and their caregivers: a pilot study.
AB  - Objective. To investigate the effects of an 8-week meditation program on
      perceived stress, sleep, mood, and related outcomes in adults with cognitive
      impairment and their caregivers. Methods. Community-dwelling adults with a
      diagnosis of mild cognitive impairment or early-stage Alzheimer's disease,
      together with their live-in caregivers, were enrolled in the study. After a brief
      training, participants were asked to meditate for 11 minutes, twice daily for 8
      weeks. Major outcomes included measures of perceived stress (Perceived Stress
      Scale), sleep (General Sleep Disturbance Scale), mood (Profile of Mood States),
      memory functioning (Memory Functioning Questionnaire), and blood pressure.
      Participants were assessed pre- and post-intervention. Results. Ten participants
      (5 of 6 dyads) completed the study. Treatment effects did not vary by participant
      status; analyses were thus pooled across participants. Adherence was good
      (meditation sessions completed/week: X = 11.4 +/- 1.1). Participants demonstrated
      improvement in all major outcomes, including perceived stress (P < 0.001), mood
      (overall, P = 0.07; depression, P = 0.01), sleep (P < 0.04), retrospective memory
      function (P = 0.04), and blood pressure (systolic, P = 0.004; diastolic, P =
      0.065). Conclusions. Findings of this exploratory trial suggest that an 8-week
      meditation program may offer an acceptable and effective intervention for
      reducing perceived stress and improving certain domains of sleep, mood, and
      memory in adults with cognitive impairment and their caregivers.

PMID- 22454691
TI  - Zerumbone, a Southeast Asian Ginger Sesquiterpene, Induced Apoptosis of
      Pancreatic Carcinoma Cells through p53 Signaling Pathway.
AB  - Pancreatic carcinoma is one common cancer with gradually increasing incidence
      during the past several decades. However, currently the candidate drugs to
      suppress pancreatic cancer remain lacking. This research was carried out to
      investigate if zerumbone, a natural cyclic sesquiterpene isolated from Zingiber
      zerumbet Smith, will produce the anticancer effects on pancreatic carcinoma cell
      lines. The results showed that zerumbone concentration, and time, dependently
      produced inhibitory actions on cell viability of PANC-1 cells. In addition,
      Hoechst 33342, AO/EB, TUNEL staining, and caspase-3 activity assay further showed
      that zerumbone induced apoptosis of PANC-1 cells. The expression of p53 protein
      was markedly upregulated, and the p21 level was also obviously elevated in
      zerumbone-treated PANC-1 cells. Moreover, ROS production was increased by about
      149% in PANC-1 cells treated by zerumbone 30 MUM. Zerumbone also produced the
      same antitumor activity in pancreatic carcinoma cell lines SW1990 and AsPC-1. In
      summary, we found that zerumbone was able to induce apoptosis of pancreatic
      carcinoma cell lines, indicating to be a promising treatment for pancreatic
      cancer.

PMID- 22454692
TI  - Antiallodynic effect of herbal medicine yokukansan on peripheral neuropathy in
      rats with chronic constriction injury.
AB  - Yokukansan, one of the traditional Japanese herbal medicines, ameliorated
      neuropathic pain symptoms in patients. In this study, we investigated the effects
      of yokukansan on neuropathic pain in chronic constriction injury (CCI) model.
      Oral administration of yokukansan significantly inhibited mechanical and cold
      allodynia in the von Frey hair or acetone test, respectively. In comparison,
      amitriptyline, a tricyclic antidepressant, demonstrated moderate, but not
      significant, antiallodynic effects in the mechanical and cold tests. Yokukansan
      significantly inhibited the cerebrospinal fluid dialysate level of glutamate that
      had increased by the stimulation of brush or acetone. Glutamate transporter
      inhibitors, DL-threo-beta-hydroxy aspartate and dihydrokainate, decreased the
      yokukansan-induced antiallodynic actions in CCI rats. Our results suggest that
      yokukansan was confirmed to have antiallodynic effects in CCI rats, which are
      related to a blockade of glutamatergic neurotransmission via activation of
      glutamate transporters in the spinal cord.

PMID- 22454693
TI  - Catenarin Prevents Type 1 Diabetes in Nonobese Diabetic Mice via Inhibition of
      Leukocyte Migration Involving the MEK6/p38 and MEK7/JNK Pathways.
AB  - Inflammation contributes to leukocyte migration, termed insulitis, and beta-cell
      loss in type 1 diabetes (T1D). Naturally occurring anthraquinones are claimed as
      anti-inflammatory compounds; however, their actions are not clear. This study
      aimed to investigate the effect and mechanism of catenarin on the inflammatory
      disease, T1D. Catenarin and/or its anthraquinone analogs dose-dependently
      suppressed C-X-C chemokine receptor type 4 (CXCR4)- and C-C chemokine receptor
      type 5 (CCR5)-implicated chemotaxis in leukocytes. Catenarin, the most potent
      anthraquinone tested in the study, prevented T1D in nonobese diabetic mice.
      Mechanistic study showed that catenarin did not act on the expression of CCR5 and
      CXCR4. On the contrary, catenarin inhibited CCR5- and CXCR4-mediated chemotaxis
      via the reduction of the phosphorylation of mitogen-activated protein kinases
      (p38 and JNK) and their upstream kinases (MKK6 and MKK7), and calcium
      mobilization. Overall, the data demonstrate the preventive effect and molecular
      mechanism of action of catenarin on T1D, suggesting its novel use as a
      prophylactic agent in T1D.

PMID- 22454694
TI  - Nonlocal means-based denoising for medical images.
AB  - Medical images often consist of low-contrast objects corrupted by random noise
      arising in the image acquisition process. Thus, image denoising is one of the
      fundamental tasks required by medical imaging analysis. Nonlocal means (NL-means)
      method provides a powerful framework for denoising. In this work, we investigate
      an adaptive denoising scheme based on the patch NL-means algorithm for medical
      imaging denoising. In contrast with the traditional NL-means algorithm, the
      proposed adaptive NL-means denoising scheme has three unique features. First, we
      use a restricted local neighbourhood where the true intensity for each noisy
      pixel is estimated from a set of selected neighbouring pixels to perform the
      denoising process. Second, the weights used are calculated thanks to the
      similarity between the patch to denoise and the other patches candidates.
      Finally, we apply the steering kernel to preserve the details of the images. The
      proposed method has been compared with similar state-of-art methods over
      synthetic and real clinical medical images showing an improved performance in all
      cases analyzed.

PMID- 22454696
TI  - Counting cells with a low-cost integrated microfluidics-waveguide sensor.
AB  - The capability to count cells from biofluids at low cost has important diagnostic
      implications in resource-poor settings. Many approaches have been developed to
      address this important need, and while most envision a low per-test cost, the
      detector instrument can be quite expensive. In this report, we present a novel
      device that enables low-cost and rapid counting of cells from a drop of blood. We
      demonstrate a shallow, buried, planar waveguide fabricated by ion exchange in
      glass that underlies a microfluidic structure for capturing cells. Laser light
      transmitted through the waveguide was attenuated by the number of metal
      nanoparticles tagged to the cells because of the interaction of the metal
      particles with the evanescent field of the waveguide. Calibration of the sensor
      using bead-tagged lymphocytes captured from human blood showed that the sensor
      could semi-quantitatively count as few as 100 cells/uL of blood. This technology
      enables the enumeration of specifically captured cells, allowing for a point-of
      care, hand-held device for fast and affordable cell counting in screening,
      remote, or resource-poor settings.

PMID- 22454697
TI  - A tribute to dr gholam a peyman.

PMID- 22454695
TI  - Hemodynamics of cerebral aneurysms: computational analyses of aneurysm progress
      and treatment.
AB  - The progression of a cerebral aneurysm involves degenerative arterial wall
      remodeling. Various hemodynamic parameters are suspected to be major mechanical
      factors related to the genesis and progression of vascular diseases. Flow
      alterations caused by the insertion of coils and stents for interventional
      aneurysm treatment may affect the aneurysm embolization process. Therefore,
      knowledge of hemodynamic parameters may provide physicians with an advanced
      understanding of aneurysm progression and rupture, as well as the effectiveness
      of endovascular treatments. Progress in medical imaging and information
      technology has enabled the prediction of flow fields in the patient-specific
      blood vessels using computational analysis. In this paper, recent computational
      hemodynamic studies on cerebral aneurysm initiation, progress, and rupture are
      reviewed. State-of-the-art computational aneurysmal flow analyses after coiling
      and stenting are also summarized. We expect the computational analysis of
      hemodynamics in cerebral aneurysms to provide valuable information for planning
      and follow-up decisions for treatment.

PMID- 22454698
TI  - Assessment of corneal quality by eye banks.

PMID- 22454699
TI  - Specular microscopic features of corneal endothelial vacuolation.
AB  - PURPOSE: To introduce a specular microscopic reference image for endothelial
      vacuolation in donated corneas. METHODS: Two corneas from a donor with diffuse,
      round to oval dark areas at the endothelial level on slit lamp biomicroscopy and
      one normal-appearing donor cornea underwent specular microscopy, histopathologic
      evaluation and transmission electron microscopy. RESULTS: Specular microscopy of
      the two corneas with abnormal-looking endothelium revealed large numbers of dark,
      round to oval structures within the endothelium in favor of endothelial
      vacuolation. Light microscopy disclosed variable sized cyst-like structures
      within the cytoplasm. Transmission electron microscopy showed electron-lucent and
      relatively large-sized intracytoplasmic vacuoles. These features were not
      observed in the endothelium of the normal cornea. CONCLUSION: The specular
      microscopic features of endothelial vacuolation in donated corneas were confirmed
      by light microscopy and transmission electron microscopy, therefore the specular
      image may be proposed as a reference to eye banks.

PMID- 22454700
TI  - The effect of mitomycin-C on corneal endothelial cells after photorefractive
      keratectomy.
AB  - PURPOSE: To evaluate short-term changes in central corneal endothelial cell
      density and morphology after photorefractive keratectomy (PRK) with mitomycin-C
      (MMC) 0.02% in patients with moderate myopia. METHODS: In this prospective
      interventional case series, patients with moderate myopia (spherical equivalent
      refractive error from -4.0 to -8.0 D) underwent PRK with a single intraoperative
      application of MMC 0.02% for 40 seconds. Specular microscopy was performed
      preoperatively and repeated 6 months after surgery to determine changes in
      central corneal endothelial cell density (ECD), mean cell area (MCA) and
      coefficient of variation in cell size (CV). RESULTS: Overall, 42 eyes of 21
      participants with mean age of 26.2+/-6.3 years underwent surgery. Mean
      preoperative spherical equivalent refractive error was -5.2+/-1.2 D which was
      reduced to -0.4+/-0.5 D postoperatively (P < 0.001). Mean ECD was reduced
      insignificantly from 2,920+/-363 cells/mm(2) preoperatively to 2,802+/-339
      cells/mm(2) postoperatively (P = 0.59). Similarly, there was no significant
      change in MCA or CV at six months (P = 0.76 and 0.52, respectively). CONCLUSION:
      Application of MMC 0.02% for 40 seconds during PRK in patients with moderate
      myopia did not significantly affect central corneal endothelial cell density and
      morphology after a 6 month follow up period.

PMID- 22454701
TI  - Correlation between Corneal Endothelial Cell Loss and Location of
      Phacoemulsification Incision.
AB  - PURPOSE: To assess the relationship between corneal endothelial cell loss after
      phacoemulsification and the location of the clear corneal incision. METHODS: A
      total of 92 patients (92 eyes) with senile cataracts who met the study criteria
      were included in this cross sectional study and underwent phacoemulsification.
      The incision site was determined based on the steep corneal meridian according to
      preoperative keratometry. Endothelial cell density was measured using specular
      microscopy in the center and 3 mm from the center of the cornea in the meridian
      of the incisions (temporal, superior, and superotemporal). Phacoemulsification
      was performed by a single surgeon using the phaco chop technique through a 3.2 mm
      clear cornea incision. Endothelial cell loss (ECL) was evaluated 1 week, and 1
      and 3 months postoperatively. RESULTS: At all time points during follow-up, ECL
      was comparable among the 3 incision sites, both in the central cornea and in the
      meridian of the incision (P > 0.05 for all comparisons). However, 3 months
      postoperatively, mean central ECL with superior incisions and mean sectoral ECL
      with temporal incisions were slightly higher. Superotemporal incisions entailed
      slightly less ECL than the other 2 groups. Overall, one month after surgery, mean
      central ECL was 10.8% and mean ECL in the sector of the incisions was 14.0%.
      Axial length and effective phaco time (EFT) were independent predictors of
      postoperative central ECL (P values 0.005 and < 0.0001, respectively).
      CONCLUSION: A superotemporal phacoemulsification incision may entail less ECL as
      compared to other incisions (although not significantly different). The amount of
      central ECL may be less marked in patients with longer axial lengths and with
      procedures utilizing less EFT.

PMID- 22454702
TI  - Delayed corneal epithelial healing after intravitreal bevacizumab: a clinical and
      experimental study.
AB  - PURPOSE: To report corneal epithelial defects (CEDs) and delayed epithelial
      healing after intravitreal bevacizumab (IVB) injection and to describe delayed
      corneal epithelial healing with topical administration of bevacizumab in an
      experimental rabbit model. METHODS: A retrospective chart review was performed on
      850 eyes of 850 patients with neovascular eye disease and diabetic macular edema
      who had received 1.25 to 2.5 mg IVB. In the experimental arm of the study,
      photorefractive keratectomy was used to create a 3 mm CED in the right eyes of 18
      New Zealand rabbits which were then randomized to three equal groups. All rabbits
      received topical antibiotics, additionally those in group A received topical
      bevacizumab and animals in group B were treated with topical corticosteroids. The
      rate of epithelial healing was assessed at different time points using slitlamp
      photography. RESULTS: In the clinical study, seven eyes of seven subjects
      developed CEDs the day after IVB injection. All of these eyes had preexisting
      corneal edema. The healing period ranged from 3 to 38 days (average 11 days)
      despite appropriate medical management. In the experimental study, topical
      bevacizumab and corticosteroids both significantly hindered corneal epithelial
      healing at 12 and 24 hours. CONCLUSION: Bevacizumab was demonstrated to cause
      CEDs in clinical settings. Moreover, corneal epithelial healing was delayed by
      topical application of bevacizumab, in the experimental model. These short-term
      results suggest that corneal edema may be considered as a risk factor for
      epithelial defects after IVB.

PMID- 22454704
TI  - Survey on Visual Impairment and Refractive Errors on Ta'u Island, American Samoa.
AB  - PURPOSE: To assess the prevalence of presenting visual impairment and refractive
      errors on the isolated island of Ta'u, American Samoa. METHODS: Presenting visual
      acuity and refractive errors of 124 adults over 40 years of age (55 male and 69
      female) were measured using the Snellen chart and an autorefractometer. This
      sample represented over 50% of the island's eligible population. RESULTS: In this
      survey, all presenting visual acuity (VA) was uncorrected. Of the included
      sample, 10.5% presented with visual impairment (visual acuity lower than 6/18,
      but equal to or better than 3/60 in the better eye) and 4.8% presented with VA
      worse than 6/60 in the better eye. Overall, 4.0% of subjects presented with
      hyperopia (+3 D or more), 3.2% were myopic (-1 D or less), and 0.8% presented
      with high myopia (-5 D or less). There was no significant difference between
      genders in terms of visual impairment or refractive errors. CONCLUSION: This
      study represents the first population-based survey on presenting visual acuity
      and refractive errors in American Samoa. In addition to providing baseline data
      on vision and refractive errors, we found that the prevalence of myopia and
      hyperopia was much lower than expected.

PMID- 22454703
TI  - Effect of cataract type and severity on visual acuity and contrast sensitivity.
AB  - PURPOSE: To determine the effect of cataract type and severity in eyes with pure
      types of age-related lens opacities on visual acuity (VA) and contrast
      sensitivity in the presence and absence of glare conditions. METHODS: Sixty
      patients with senile cataracts aged 40 years or older with no other ocular
      pathologies were evaluated for VA and contrast sensitivity with and without
      glare. Lens opacities were classified according to the Lens Opacities
      Classification System (LOCS) III. VA was measured using the Snellen chart.
      Contrast sensitivity was measured with the Vector Vision CSV-1000E chart in the
      presence and absence of glare by calculating the area under log contrast
      sensitivity (log CS) function (AULCSF). RESULTS: Cataracts were posterior
      subcapsular in 26 eyes, cortical in 19 eyes and nuclear in 15 eyes. VA
      significantly decreased with increasing cataract severity and there was
      significant loss of contrast sensitivity at all spatial frequencies with
      increasing cataract severity. AULCSF significantly decreased with increasing
      cataract severity in the presence and absence of glare conditions. Contrast
      sensitivity was significantly reduced at high spatial frequency (18 cpd) in
      cortical cataracts in the presence of glare in day light and at low spatial
      frequency (3 cpd) in night light. CONCLUSION: Increased cataract severity is
      strongly associated with a decrease in both VA and AULCSF. Contrast sensitivity
      scores may offer additional information over standard VA tests in patients with
      early age-related cataracts.

PMID- 22454705
TI  - Combination therapies in ophthalmology: implications for intravitreal delivery.
AB  - Most pathological processes involve complex molecular pathways that can only be
      modified or blocked by a combination of medications. Combination therapy has
      become a common practice in medicine. In ophthalmology, this approach has been
      used effectively to treat bacterial, fungal, proliferative/neoplastic, and
      inflammatory eye diseases and vascular proliferation. Combination therapy also
      encompasses the synergistic effect of electromagnetic radiation and medications.
      However, combination therapy can augment inherent complications of individual
      interventions, therefore vigilance is required. Complications of combination
      therapy include potential incompatibility among compounds and tissue toxicity.
      Understanding these effects will assist the ophthalmologist in his decision to
      maximize the benefits of combination therapy while avoiding an unfavorable
      outcome.

PMID- 22454706
TI  - Non-Hodgkin's Lymphoma Presenting as a Huge Ocular Adnexal and Forehead Mass.
AB  - PURPOSE: To report a case of non-Hodgkin's lymphoma (NHL) presenting as an ocular
      adnexal and forehead mass. CASE REPORT: An elderly male patient was referred by a
      neurosurgeon to the eye clinic with a six-month history of a massive tumor
      measuring 12*16*8 cm involving the right side of the forehead, eyebrow and upper
      eyelid. Neurological examination had been normal and computed tomography revealed
      no intracranial extension. The patient was referred to an otorhinolaryngologist
      who performed an incisional biopsy which revealed the mass to be NHL. He received
      chemotherapy with CHOP regimen (cyclophosphamide, adriamycin, vincristine and
      prednisolone) resulting in reduction in lesion size leaving a phthysical eyeball
      and a ptotic lid. CONCLUSION: Non-Hodgkin's lymphoma may occur in almost any part
      of the body and should be considered in the differential diagnosis of
      extralymphoid tumors.

PMID- 22454707
TI  - Sudden onset and blinding spontaneous direct carotid-cavernous fistula.
AB  - PURPOSE: To report a case of spontaneous direct carotid-cavernous fistula causing
      abrupt loss of vision. CASE REPORT: A 50-year-old woman with systemic
      hypertension but no history of ocular disease developed sudden proptosis, frozen
      eye, subconjunctival hemorrhage and loss of vision in her left eye over 2 hours.
      Imaging studies revealed a direct carotid-cavernous fistula. Management for high
      intraocular pressure was promptly initiated and the patient was referred to a
      neurosurgery service, but she refused any surgical intervention. Ultimately, she
      accepted to undergo manual carotid artery compression which resulted in
      significant reduction in the proptosis, but she lost all vision permanently.
      CONCLUSION: Direct carotid-cavernous fistula can occur spontaneously and should
      be taken into account in patients with signs suggestive of direct carotid
      cavernous sinus fistula even without history of trauma or connective tissue
      disorder.

PMID- 22454708
TI  - Bilateral elevated macular lesions.

PMID- 22454709
TI  - Bilateral premacular subhyaloid hemorrhage in dengue Fever.

PMID- 22454710
TI  - A technique to salvage big-bubble deep anterior lamellar keratoplasty after
      inadvertent full-thickness trephination.
AB  - Herein we describe a technique for management of large inadvertent full-thickness
      trephination during deep anterior lamellar keratoplasty using the big-bubble
      technique without converting to penetrating keratoplasty. First, the anterior
      chamber is formed with an ophthalmic viscosurgical device (OVD). Then, the full
      thickness wound is secured with one X-type 10-0 nylon suture. A 27-gauge needle
      is attached to a 2 ml air-filled syringe and inserted into the corneal stroma in
      the meridian opposite to the site of full-thickness trephination. Air is gently
      injected to produce a limited area of "big-bubble" detaching Descemet's membrane
      (DM) from the corneal stroma. The "big bubble" is slowly expanded with injection
      of OVD. Finally, the recipient stroma is removed, the donor lenticule is placed
      and the DM tear is secured with one full thickness 10-0 nylon suture.

PMID- 22454711
TI  - Human cadaveric retinal cultures: an experimental tool for retinal regeneration.

PMID- 22454712
TI  - Retinal redetachment after cataract surgery in eyes with previous scleral
      buckling.

PMID- 22454713
TI  - Erythropoietin; a novel neuroprotective agent for ocular disorders.

PMID- 22454714
TI  - Postoperative bleb management with topical mitomycin-C.

PMID- 22454715
TI  - Topical Mitomycin-C versus Subconjunctival 5-Fluorouracil for Management of Bleb
      Failure.
AB  - PURPOSE: To compare the efficacy and safety of topical mitomycin-C (MMC) drops
      with that of subconjunctival 5-fluorouracil (5-FU) injections for management of
      early bleb failure after trabeculectomy or combined phacoemulsification and
      trabeculectomy with posterior chamber intraocular lens implantation (PT+PCIOL).
      METHODS: In a randomized comparative study, 37 eyes of 37 patients with impending
      early bleb failure received MMC 0.02% eye drops for 2 or 4 weeks (19 eyes) or
      subconjunctival 5-FU injections, 5 mg per dose (18 eyes). Complete success was
      defined as 5 < IOP <= 18 mmHg without medications. RESULTS: Baseline
      characteristics were comparable between the study groups. However, there were
      more cases of combined PT+PCIOL in the MMC group [11 (57.9%) eyes versus 3
      (16.7%) eyes, P = 0.017]. Mean preoperative IOP was 20.5+/-8.85 mmHg in the MMC
      group and 25.82+/-11.35 mmHg in the 5-FU group (P = 0.129), which was decreased
      to 13.2+/-6.1 and 10.6+/-4.8 mmHg respectively after 12 months (P = 0.159). There
      was no significant difference between the study groups in terms of bleb extent (P
      = 0.170), height (P = 0.178) or vascularity (P = 0.366). At the end of the study,
      complete success was achieved in 13 eyes (68.4%) in the MMC group and 14 eyes
      (77.8%) in the 5-FU group (P = 0.714). The survival of success at 8 months
      (median follow-up) was 89.5% and 86.5% in the MMC and 5-FU groups respectively;
      the number of glaucoma medications (P = 0.707) and best-corrected visual acuity
      (P = 0.550) were also comparable. Complication rates were similar in the study
      groups (P = 0.140). CONCLUSION: Topical MMC 0.02% has comparable safety and
      efficacy to subconjunctival 5-FU injections for management of early bleb failure.
      Topical MMC 0.02% drops are more convenient and can be initiated first, while 5
      FU injections may be reserved for eyes with an insufficient response to topical
      MMC.

PMID- 22454716
TI  - Characteristics of keratoconus patients at a tertiary eye center in India.
AB  - PURPOSE: To evaluate the presentation and characteristics of patients with
      keratoconus at a tertiary eye care center in Mumbai, India. METHODS: This single
      center, non-comparative, retrospective cohort analysis was performed on patients
      with keratoconus who presented to the Clear Vision Eye Center clinic from April
      2007 to March 2009. Data was collected to characterize correlations among visual
      acuity, corneal biomicroscopic findings, and refractive and topographic findings
      in keratoconus. RESULTS: Records of 274 patients including 189 male and 85 female
      subjects with mean age of 20.1+/-3.5 (range, 13 to 29) years at the time of
      diagnosis were assessed. There was history of skin allergy in 73 (26.6%),
      symptomatic ocular allergy in 67 (24.45%) and asthma in 31 (11.31%) patients. The
      most frequent corneal sign was Fleischer's ring which was observed in 81% of
      cases. Corneal topography revealed mean simK (simulated keratometry) of 53.3+/
      6.1 (range, 41.2 to 69.0) diopters. Corneal topography analysis with the Cone
      Location Magnitude Index disclosed the presence of inferior cones in 93% of
      patients. CONCLUSION: This group of patients had younger age at presentation and
      more severe keratoconus as compared to western populations; contact lenses were
      used only in a minority of patients.

PMID- 22454717
TI  - Orthoptic Changes following Photorefractive Keratectomy.
AB  - PURPOSE: To report orthoptic changes after photorefractive keratectomy (PRK).
      METHODS: This interventional case series included 297 eyes of 150 patients
      scheduled for PRK. Complete ophthalmologic evaluations focusing on orthoptic
      examinations were performed before and 3 months after PRK. RESULTS: Before PRK, 2
      (1.3%) patients had esotropia which remained unchanged; 3 (2%) patients had far
      exotropia which improved after the procedure. Of 12 cases (8%) with initial
      exotropia at near, 3 (2%) cases became orthophoric, however 6 patients (4%)
      developed new near exotropia. A significant reduction in convergence and
      divergence amplitudes (P < 0.001) and a significant increase in near point of
      convergence (NPC) (P < 0.006) were noticed after PRK. A reduction >= 10 PD in
      convergence amplitude and >= 5 PD in divergence amplitude occurred in 10 and 5
      patients, respectively. Four patients had initial NPC > 10 cm which remained
      unchanged after surgery. Out of 9 (6%) patients with baseline stereopsis > 60
      seconds of arc, 2 (1.33%) showed an improvement in stereopsis following PRK. No
      patient developed diplopia postoperatively. CONCLUSION: Preexisting strabismus
      may improve or remain unchanged after PRK, and new deviations can develop
      following the procedure. A decrease in fusional amplitudes, an increase in NPC,
      and an improvement in stereopsis may also occur after PRK. Preoperative
      evaluation of orthoptic status for detection of baseline abnormalities and
      identification of susceptible patients seem advisable.

PMID- 22454718
TI  - Intravitreal triamcinolone for acute branch retinal vein occlusion: a randomized
      clinical trial.
AB  - PURPOSE: To evaluate the therapeutic effect of intravitreal triamcinolone (IVT)
      injection for recent branch retinal vein occlusion (BRVO). METHODS: In a
      randomized controlled clinical trial, 30 phakic eyes with recent (less than 10
      weeks' duration) BRVO were assigned to two groups. The treatment group (16 eyes)
      received 4 mg IVT and the control group (14 eyes) received subconjunctival sham
      injections. Changes in visual acuity (VA) were the main outcome measure. RESULTS:
      VA and central macular thickness (CMT) changes were not significantly different
      between the study groups at any time point. Within group analysis showed
      significant VA improvement from baseline in the IVT group up to three months (P <
      0.05); the amount of this change was -0.53 +/- 0.46, -0.37 +/- 0.50, -0.46 +/-
      0.50, and -0.29 +/- 0.45 logMAR at 1, 2, 3, and 4 months, respectively.
      Corresponding VA improvements in the control group were -0.20 +/- 0.37, -0.11 +/-
      0.46, -0.25 +/- 0.58, and -0.05 +/- 0.50 logMAR (all P values > 0.05).
      Significant reduction in CMT was noticed only in the treatment group (-172 +/-
      202 MUm, P = 0.029) and at 4 months. Ocular hypertension occurred in 4 (25%) and
      2 (14.3%) eyes in the IVT and control groups, respectively. CONCLUSION: A single
      IVT injection had a non-significant beneficial effect on VA and CMT in acute BRVO
      as compared to the natural history of the condition. The 3-month deferred
      treatment protocol advocated by the Branch Vein Occlusion Study Group may be a
      safer option than IVT injection considering its potential side effects.

PMID- 22454719
TI  - Electroretinogram Changes following Silicone Oil Removal.
AB  - PURPOSE: To evaluate electroretinogram (ERG) changes after silicone oil removal.
      METHODS: Scotopic and photopic ERGs, and best-corrected visual acuity (BCVA) were
      checked before and shortly after silicone oil removal in eyes that had previously
      undergone vitrectomy and silicone oil injection for complex retinal detachment.
      Pre- and postoperative ERG a- and b-wave amplitudes were compared. RESULTS:
      Twenty-eight eyes of 28 patients including 20 male and 8 female subjects with
      mean age of 39.3 +/- 0.06 (range, 12 to 85) years were studied. Mean interval
      from primary vitreoretinal surgery to silicone oil removal was 21.04 +/- 0.52
      (range, 7 to 39) months. Mean duration from silicone oil removal to second ERG
      was 13.04 +/- 1.75 (range, 10 to 16) days. Before silicone oil removal, mean a
      wave amplitudes in maximal combined response, rod response and cone response ERGs
      were 27.4 +/- 19.9, 7.2 +/- 4.5 and 5.5 +/- 3.4 MUv, respectively. These values
      increased to 48.8 +/- 31.9, 15.1 +/- 14.4 and 17.4 +/- 22.2 MUv, respectively
      after silicone oil removal (P < 0.001). Mean b-wave amplitudes in the same order,
      were 69.41 +/- 51, 41.2 +/- 30.4 and 25.1 +/- 33.9 MUv before silicone oil
      removal, increasing to 165.6 +/- 102.5, 81.7 +/- 53.7 and 44.7 +/- 34.1 MUv
      respectively, after silicone oil removal (P < 0.001). Mean BCVA significantly
      improved from 1.10 +/- 0.34 at baseline to 1.02 +/- 0.33 logMAR after silicone
      oil removal (P < 0.001). CONCLUSION: The amplitudes of ERG a- and b-waves under
      scotopic and photopic conditions increased significantly shortly after silicone
      oil removal. An increase in BCVA was also observed. These changes may be
      explained by the insulating effect of silicone oil on the retina.

PMID- 22454720
TI  - Pattern of ocular injuries in owo, Nigeria.
AB  - PURPOSE: To determine the pattern of ocular injuries in patients presenting to
      the eye clinic and the accident and emergency department of Federal Medical
      Center, Owo, Ondo State, Nigeria. METHODS: This prospective study was conducted
      between January and December 2009. Federal Medical Center, Owo is the only
      tertiary hospital in Ondo State, Nigeria. The eye center located at this medical
      center was the only eye care facility in the community at the time of this study.
      All patients were interviewed with the aid of an interviewer-administered
      questionnaire and underwent a detailed ocular examination. RESULTS: Of 132
      patients included in the study, most (84.1%) sustained blunt eye injury while
      (12.1%) had penetrating eye injury. A considerable proportion of patients (37.9%)
      presented within 24 hours of injury. Vegetative materials were the most common
      (42.4%) offending agent, a minority of patients (22%) was admitted and none of
      the patients had used eye protection at the time of injury. CONCLUSION: In the
      current series, blunt eye injury was the most common type of ocular trauma. The
      community should be educated and informed about the importance of preventive
      measures including protective eye devices during high risk activities. Patients
      should be encouraged to present early following ocular injury.

PMID- 22454721
TI  - Functional assessment of magno, parvo and konio-cellular pathways; current state
      and future clinical applications.
AB  - The information generated by cone photoreceptors in the retina is compressed and
      transferred to higher processing centers through three distinct types of ganglion
      cells known as magno, parvo and konio cells. These ganglion cells, which travel
      from the retina to the lateral geniculate nucleus (LGN) and then to the primary
      visual cortex, have different structural and functional characteristics, and are
      organized in distinct layers in the LGN and the primary visual cortex. Magno
      cells are large, have thick axons and usually collect input from many retinal
      cells. Parvo cells are smaller, with fine axons and less myelin than mango cells.
      Konio cells are diverse small cells with wide fields of input consisting of
      different cells types. The three cellular pathways also differ in function. Magno
      cells respond rapidly to changing stimuli, while parvo cells need time to
      respond. The distinct patterns of structure and function in these cells have
      provided an opportunity for clinical assessment of their function. Functional
      assessment of these cells is currently used in the field of ophthalmology where
      frequency-doubling technology perimetry selectively assesses the function of
      magno cells. Evidence has accrued that the three pathways show characteristic
      patterns of malfunctions in multiple sclerosis, schizophrenia, Parkinson's and
      Alzheimer's diseases, and several other disorders. The combination of behavioral
      assessment with other techniques, such as event related potentials and functional
      magnetic resonance imaging, seems to bear promising future clinical applications.

PMID- 22454722
TI  - Immunologic corneal graft rejection after administration of topical latanoprost:
      a report of two patients.
AB  - PURPOSE: To report endothelial corneal graft rejection after administration of
      topical latanoprost eye drops. CASE REPORT: Two eyes of two patients with a
      history of multiple intraocular procedures prior to penetrating keratoplasty
      developed endothelial graft rejection one month after administration of topical
      latanoprost. Cystoid macular edema developed simultaneously in one patient.
      CONCLUSION: Latanoprost may trigger endothelial graft rejection in susceptible
      eyes.

PMID- 22454723
TI  - Graft suturing for lenticule dislocation after descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To report the mid-term outcomes of graft suturing in a patient with
      lenticule dislocation after Descemet stripping automated endothelial keratoplasty
      (DSAEK). CASE REPORT: A 78-year old woman was found to have graft dislocation
      involving the nasal half of the cornea after uneventful DSAEK. Graft
      repositioning, refilling the anterior chamber with air, and placement of four
      full-thickness 10/0 nylon sutures over the detached area were performed two weeks
      after the initial surgery. The sutures were removed 6 weeks later. Serial
      specular microscopy and anterior segment optical coherence tomography were
      performed. At 18 months, there was good lenticule apposition and a clear graft.
      CONCLUSION: Anchoring sutures seem to be effective for management of graft
      detachment following DSAEK.

PMID- 22454724
TI  - Minimally invasive vitreoretinal surgery: is sutureless vitrectomy the future of
      vitreoretinal surgery?

PMID- 22454725
TI  - Nanophthalmos.

PMID- 22454726
TI  - Staged penetrating sclerokeratoplasty and penetrating keratoplasty for management
      of advanced acquired anterior staphyloma.
AB  - Herein we describe a staged surgical technique consisting of penetrating
      sclerokeratoplasty (PSKP) followed by penetrating keratoplasty (PKP) and present
      its clinical course and complications over two years of follow-up. A 23-year-old
      man presented with cosmetically unacceptable protrusion of the globe
      corresponding to the cornea and sclera. PSKP was performed transplanting a full
      thickness beveled 13 mm corneoscleral tectonic graft. Hypotony developed
      subsequently and was successfully managed medically, however corneal graft
      failure occurred. After 15 months, a 7.5 mm PKP was performed for optical
      reasons, which subsequently remained clear with a healthy epithelium. In this
      particular case, cosmetic, tectonic, therapeutic, and optical requirements were
      met. PSKP is a surgical procedure which entails a high rate of complications but
      may be the only alternative when the main goal of intervention is restoration of
      the globe in complicated cases such as our patient.

PMID- 22454727
TI  - Femtosecond laser cataract surgery.

PMID- 22454728
TI  - Collagen crosslinking for keratoconus.

PMID- 22454729
TI  - Short-term Outcomes of Collagen Crosslinking for Early Keratoconus.
AB  - PURPOSE: To assess the efficacy of collagen crosslinking with riboflavin and
      ultraviolet A (UVA) radiation for treatment of early keratoconus. METHODS: Thirty
      one eyes of 22 patients with early keratoconus were included in this study. All
      patients underwent slit lamp examination and assessment of uncorrected visual
      acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), intraocular
      pressure, corneal topography and pachymetry. Collagen crosslinking was performed
      without epithelial removal. Riboflavin was applied to the cornea every 3 minutes
      30 minutes before UVA irradiation and every 5 minutes thereafter. Patients were
      re-assessed 1, 3, and 6 months after treatment. RESULTS: Postoperatively, UCVA
      increased by 2 Snellen lines and BSCVA was improved by 1.7 Snellen lines (P <
      0.001). Spherical equivalent refractive error was reduced by 0.55 D, and maximum
      and mean K values were decreased by 0.65 D and 0.51 D respectively (P < 0.05 for
      all comparisons). Evidence of regression was present in 71% of treated eyes.
      CONCLUSION: Collagen crosslinking demonstrated significant improvement in vision
      with reduction in corneal power and spherical equivalent refractive error in eyes
      with early keratoconus.

PMID- 22454730
TI  - IOLMaster versus Manual Keratometry after Photorefractive Keratectomy.
AB  - PURPOSE: To compare keratometric measurements using a Javal type manual
      keratometer with IOLMaster in eyes undergoing photorefractive keratectomy (PRK)
      for myopia. METHODS: In this comparative case series, we studied patients aged 21
      to 27 years scheduled for myopic PRK. Keratometry was performed preoperatively
      and three months after the procedure using a Javal type manual keratometer and
      the IOLMaster. We compared postoperative measurements obtained by both
      instruments with the clinical history method (CHM). RESULTS: Seventy eyes of 35
      patients with mean age of 23.45+/-1.55 years were studied. Mean preoperative
      spherical equivalent was -4.53+/-1.3 D. Average preoperative IOLMaster and manual
      keratometric readings were 45.95+/-1.23 D and 46.32+/-1.18 D, respectively.
      Postoperatively, mean IOLMaster measurements was 38.03+/-0.68 D and that of
      manual keratometry was 43.15+/-1.1 D. Compared to CHM measurements, the 95%
      limits of agreement were -5.95 to -0.85 for the IOLMaster and -1.44 to 4.04 for
      manual keratometry. CONCLUSION: Keratometric measurements with the IOLMaster and
      a Javal type manual device are comparable after PRK; both are largely deviant
      from the CHM and can yield misleading results.

PMID- 22454731
TI  - Oscillatory photodynamic therapy for choroidal neovascularization and central
      serous retinopathy; a pilot study.
AB  - PURPOSE: To report the preliminary results of oscillatory photodynamic therapy
      (OPDT) for choroidal neovascularization (CNV) and central serous retinopathy
      (CSR). METHODS: This study included 7 eyes of 6 patients with CSR (2 eyes),
      idiopathic CNV (2 eyes), CNV due to age-related macular degeneration (AMD) (2
      eyes), and peripapillary CNV secondary to presumed ocular histoplasmosis syndrome
      (1 eye). Intravenous verteporfin (6 mg/m(2) body surface area) was infused over
      10 minutes followed by oscillating laser (wavelength 689 nm) covering slightly
      beyond the entire lesion. An Area Centralis lens was applied and laser was
      delivered (600 mW/cm(2) fluence rate and 50 J/cm(2) dose). Intravitreal
      bevacizumab and dexamethasone combination therapy was used with OPDT in 4 eyes
      with CNV; intravitreal dexamethasone and triamcinolone acetonide were injected in
      the other eye with CNV. Clinical examination, funduscopy, fluorescein
      angiography, and optical coherence tomography (OCT) were performed at baseline
      and after treatment. RESULTS: After mean follow-up of 7.1+/-5.1 months, visual
      acuity improved from 0.87+/-0.69 logMAR (20/160) to 0.60+/-0.65 logMAR (20/80) (P
      = 0.027); central foveal thickness decreased from 322+/-62.1 to 240.7+/-34.8
      microns as measured by OCT (P = 0.018). Fluorescein angiography and OCT
      demonstrated cessation of vascular leakage, and resolution of hemorrhage and
      subretinal fluid in all eyes. No adverse events or recurrence were noted.
      CONCLUSION: OPDT was effective in treating CNV lesions and CSR. OPDT may be an
      improvement on standard PDT due to reduced side effects, thermal damage and
      scarring.

PMID- 22454732
TI  - Adjunctive Local Application of Lidocaine during Scleral Buckling under General
      Anesthesia.
AB  - PURPOSE: To evaluate the effect of local lidocaine application on the incidence
      of the oculocardiac reflex (OCR) during scleral buckling (SB) for rhegmatogenous
      retinal detachment (RRD) under general anesthesia. METHODS: In a randomized
      clinical trial, eyes with RRD scheduled for SB under general anesthesia were
      randomized to adjunctive local application of 1 ml lidocaine 2% versus normal
      saline to the muscles after conjunctival opening. Surgical stimulation was
      initiated 5 minutes afterwards. Additionally, 100 mg of lidocaine 2% was added to
      50 ml of normal saline in the treatment group which was used for irrigation
      during surgery; control eyes were irrigated with normal saline. The incidence of
      the OCR, rate of postoperative nausea/vomiting (PONV), total intravenous (IV)
      analgesic dose, duration of surgery, and period of hospitalization were compared
      between the study groups. RESULTS: Thirty eyes of 30 patients including 22
      (73.3%) male and 8 (26.7%) subjects with mean age of 49.4+/-16.3 years were
      operated. OCR and PONV occurred less frequently, and total intravenous analgesic
      dose was significantly lower in the lidocaine group (P < 0.05 for all
      comparisons). However, no significant difference was noted between the study
      groups in terms of duration of surgery and period of hospitalization. CONCLUSION:
      Adjunctive local application of lidocaine during SB under GA for RRD decreases
      the rate of OCR and PONV, reduces the intravenous analgesic dose, but does not
      affect the duration of surgery or hospitalization.

PMID- 22454733
TI  - Increased Latency of Visual Evoked Potentials in Healthy Women during
      Menstruation.
AB  - PURPOSE: To evaluate the latency of visual evoked potentials (VEPs) in healthy
      women during and after menstruation. METHODS: Pattern and flash VEPs were
      performed in 15 healthy women aged 18 to 25 years on the maximum bleeding day
      (luteal phase) and 7 days after the menstrual cycle (follicular phase). RESULTS:
      Mean latency was 119.6 msec on the maximum bleeding day and 100.8 msec one week
      after menstruation on pattern VEP (P < 0.001). Corresponding values for flash VEP
      were 124.5 msec and 112.7 msec, respectively (P < 0.001). CONCLUSION: Prolonged
      VEP latency on the maximum bleeding day indicates that high progesterone levels
      may have an inhibitory effect on optic nerve conduction velocity.

PMID- 22454734
TI  - Visual Fields at Presentation and after Trans-sphenoidal Resection of Pituitary
      Adenomas.
AB  - PURPOSE: To evaluate visual field changes in patients with pituitary adenomas
      following trans-sphenoidal surgery. METHODS: Eighteen patients with pituitary
      adenomas underwent a complete ophthalmic assessment and visual field analysis
      using the Humphrey Field Analyzer 30-2 program before and after trans-sphenoidal
      surgical resection at the Himalayan Institute of Medical Sciences over a one year
      period. Visual acuity, duration of symptoms, optic nerve head changes, pattern of
      visual field defects, and variables such as mean deviation and visual field index
      were compared. RESULTS: Thirty-six eyes of 18 patients including 10 male and 8
      female subjects with mean age of 35.1+/-9.9 years and histologically proven
      pituitary adenoma were included. Mean visual acuity at presentation was 0.29
      logMAR which improved to 0.21 logMAR postoperatively (P = 0.305). Of 36 eyes, 24
      (66.7%) had visual field defects including temporal defects in 12 eyes (33.3%),
      non-specific defects in 10 eyes (27.8%), and peripheral field constriction in 2
      eyes (5.6%). Mean deviation of visual fields at presentation was -14.28 dB which
      improved to -11.32 dB postoperatively. The visual field index improved from 63.5%
      to 75% postoperatively. Favorable visual field outcomes were correlated with
      shorter duration of symptoms and absence of optic nerve head changes at
      presentation. CONCLUSION: Visual field defects were present in two thirds of
      patients at presentation. An overall improvement in vision and visual fields was
      noted after surgical resection. An inverse correlation was found between the
      duration of symptoms and postoperative visual field recovery, signifying the
      importance of early surgical intervention.

PMID- 22454735
TI  - Dry eye syndrome.
AB  - Our understanding of keratoconjunctivitis sicca (KCS), also known as dry eye
      syndrome, has been changed over recent years. Until lately, the condition was
      thought to be merely due to aqueous tear insufficiency. Today, it is understood
      that KCS is a multifactorial disorder due to inflammation of the ocular surface
      and lacrimal gland, neurotrophic deficiency and meibomian gland dysfunction. This
      change in paradigm has led to the development of new and more effective
      medications.

PMID- 22454736
TI  - Orbital myiasis.
AB  - PURPOSE: To present a case of massive orbital myiasis. CASE REPORT: An 87-year
      old debilitated woman suffering from left ocular pain of four days' duration
      presented with a severely necrotized left orbit and several attached live larvae.
      The upper and lower eyelids and the eyeball were completely destroyed. She had
      history of eyelid surgery in the same eye due to a skin lesion, apparently some
      type of skin cancer, 15 years before. The larvae were identified as Chrysomya
      bezziana (Diptera: Calliphoridae) or old world screwworm fly. CONCLUSION:
      Infestation of ocular and orbital tissues by fly larvae (ophthalmomyiasis)
      progresses rapidly and can completely destroy orbital tissues within days,
      especially in patients with poor general health. Treatment consists of removal of
      the larvae and surgical debridement.

PMID- 22454737
TI  - Tuberculous orbital abscess associated with thyroid tuberculosis.
AB  - PURPOSE: To report an unusual presentation of tuberculosis. CASE REPORT: A six
      year old boy presented with left upper lid swelling of 15 days' duration and an
      asymptomatic midline neck mass from 2 months ago. Imaging studies, and
      microbiologic tests which demonstrated acid-fast bacilli in the fine needle
      aspirate of the thyroid mass, both confirmed a diagnosis of cold tuberculous
      thyroid abscess with presumed hematogenous spread to the orbit. The patient
      demonstrated marked improvement of both lesions with antitubercular drugs.
      CONCLUSION: This case illustrates a very rare association of orbital and thyroid
      tuberculosis.

PMID- 22454738
TI  - Glaucoma in a patient with nanophthalmos.

PMID- 22454739
TI  - Bilateral orbital mass lesions: a presentation of Wegener's granulomatosis.

PMID- 22454740
TI  - Non-endoscopic Mechanical Endonasal Dacryocystorhinostomy.
AB  - To circumvent the disadvantages of endoscopic dacryocystorhinostomy such as small
      rhinostomy size, high failure rate and expensive equipment, we hereby introduce a
      modified technique of non-endoscopic mechanical endonasal dacryocystorhinostomy
      (NE-MEDCR). Surgery is performed under general anesthesia with local decongestion
      of the nasal mucosa. A 20-gauge vitrectomy light probe is introduced through the
      upper canaliculus until it touches the bony medial wall of the lacrimal sac.
      While directly viewing the transilluminated target area, a nasal speculum with a
      fiber optic light carrier is inserted. An incision is made vertically or in a
      curvilinear fashion on the nasal mucosa in the lacrimal sac down to the bone
      using a Freer periosteum elevator. Approximately 1 to 1.5 cm of nasal mucosa is
      removed with Blakesley forceps. Using a lacrimal punch, the thick bone of the
      frontal process of the maxilla is removed and the inferior half of the sac is
      uncovered. The lacrimal sac is tented into the surgical site with the light probe
      and its medial wall is incised using a 3.2 mm keratome and then excised using the
      Blakesley forceps. The procedure is completed by silicone intubation. The NE
      MEDCR technique does not require expensive instrumentation and is feasible in any
      standard ophthalmic surgical setting.

PMID- 22454741
TI  - Contribution of Iran to the Ophthalmic Literature over the Past Three Decades.

PMID- 22454742
TI  - ARVO 2011: Visionary Genomics.

PMID- 22454743
TI  - JOVR is Promoting Closer Academic and Scientific Ties between Europe and Iran.

PMID- 22454744
TI  - JOVR Uveitis Issue; Partnership between European and Middle Eastern
      Ophthalmologists.

PMID- 22454745
TI  - Patterns of uveitis in the middle East and europe.
AB  - PURPOSE: To compare the patterns of uveitis, emphasizing similarities and
      discrepancies, in the Middle East and Europe. METHODS: Six articles reporting
      uveitis patterns from the Middle East including a total of 2,693 cases, and seven
      articles with a sum of 4,379 cases from Europe were analyzed and patterns in each
      region were defined and compared. RESULTS: In both regions, uveitis was most
      commonly seen in the fourth decade of life with anterior uveitis being the most
      common anatomical form. Idiopathic cases accounted for the majority of anterior
      and intermediate uveitis; toxoplasmosis was the most frequent entity in posterior
      uveitis while Behcet's disease and idiopathic forms were the next most common
      causes in the Middle East and in Europe, respectively. CONCLUSION: Since patterns
      of uveitis differ in various geographic regions, discovering these patterns would
      be helpful for the diagnosis and treatment of this broad category of conditions.
      This necessitates applying a universal diagnostic classification system to enable
      accurate comparisons.

PMID- 22454746
TI  - Indocyanine green angiography guided management of vogt-koyanagi-harada disease.
AB  - PURPOSE: To report the management of Vogt-Koyanagi-Harada (VKH) disease based on
      indocyanine green angiography (ICGA). METHODS: VKH patients with acute episodes
      of inflammation (inaugural or recurrent) who had received standard ICGA-guided
      care were studied retrospectively. Standard of care included high dose systemic
      corticosteroids at presentation and close ICGA follow-up with addition of
      immunosuppressive agents and/or intensification of ongoing therapy when recurrent
      choroidal lesions were detected by ICGA. Visual acuity, number of subclinical
      recurrences, type and duration of therapy, proportion of quiescent patients after
      therapy, and ICGA findings were recorded. RESULTS: Nine patients including 8
      female and one male subject were studied. Five patients had inaugural disease and
      4 presented with recurrent acute episodes. Visual acuity increased from 0.86+/
      0.36 to 1.14+/-0.34 in the right eyes, and from 0.77+/-0.34 to 1.05+/-0.33 in the
      left eyes. The number of ICGA-detected occult choroidal recurrences amounted to
      13. Mean duration of treatment was 30.1+/-34.6 months leading to recurrence-free
      status after discontinuation of therapy in 6 cases with mean duration of 29.5
      months. CONCLUSION: Continuous monitoring and aggressive therapy guided by ICGA
      in VKH disease prolongs treatment as compared to textbook guidelines but offers
      the prospect of reaching inflammation-free status after discontinuation of
      therapy. Zero tolerance to subclinical choroidal inflammation avoids irremediable
      evolution towards sunset glow fundus in patients treated early after the initial
      acute inflammatory attack.

PMID- 22454747
TI  - Childhood pars planitis; clinical features and outcomes.
AB  - PURPOSE: To evaluate the demographic and clinical features of childhood pars
      planitis, and to determine the therapeutic and visual outcomes of the disease.
      METHODS: Medical records of pediatric patients (less than 16 years of age at
      diagnosis) with pars planitis and at least 6 months of follow-up who were
      referred to Labbafinejad Medical Center, Tehran, Iran over a 22 year period were
      reviewed. RESULTS: Overall, 117 eyes of 61 patients including 51 (83.6%) male
      subjects were included. Mean age at the time of diagnosis was 7.8+/-3.2 (range, 3
      16) years. Mean best corrected visual acuity (BCVA) was 0.88+/-0.76 logMAR at
      presentation which improved to 0.39+/-0.51 logMAR at final visit (P<0.001).
      Endotheliitis was present in 23 (19.6%) eyes and was significantly more prevalent
      in subjects younger than 9 years (P=0.025). Cataract formation (41.9%) and
      cystoid macular edema (19.7%) were the most prevalent complications. Univariate
      regression analysis showed that better baseline visual acuity (OR=0.38, 95%CI
      0.21-0.70, P=0.002), age older than 5 years at disease onset (OR=0.36, 95%CI 0.14
      0.9, P=0.029), absence of endotheliitis (OR=0.39, 95%CI 0.15-0.99, P=0.047) and
      female gender (OR=3.77, 95%CI 1.03-13.93, P=0.046) were significantly associated
      with final BCVA of 20/40 or better. CONCLUSION: Childhood pars planitis was much
      more common among male subjects. Endotheliitis may be a sign of inflammation
      spillover and is more prevalent in younger patients. Visual prognosis is
      favorable in most patients with appropriate treatment.

PMID- 22454748
TI  - Confocal Scan Features of Keratic Precipitates in Granulomatous versus
      Nongranulomatous Uveitis.
AB  - PURPOSE: To compare the morphologic features of keratic precipitates (KPs) by
      confocal microscopy in granulomatous versus nongranulomatous noninfectious
      uveitis. METHODS: KP morphology was determined by confocal scan in patients with
      noninfectious granulomatous and noninfectious nongranulomatous uveitic cases.
      RESULTS: One hundred and twenty-seven eyes of 90 subjects with noninfectious
      uveitis were studied. Thirty-nine eyes had granulomatous and 88 had
      nongranulomatous uveitis. Smooth-rounded KPs were significantly more common in
      the granulomatous subgroup (P<0.001) while cruciform and dendritiform KPs were
      more frequent in nongranulomatous uveitis (P<0.001 and P<0.005 respectively).
      CONCLUSION: Confocal scan may be used as an adjunctive tool for differentiating
      granulomatous from nongranulomatous uveitis. Smooth-rounded KPs are strongly
      suggestive of granulomatous inflammation.

PMID- 22454749
TI  - Pediatric uveitis.
AB  - Uveitis is less common in children than in adults, and its diagnosis and
      management can be particularly challenging. Young children are often asymptomatic
      either because of inability to express complaints or because of the truly
      asymptomatic nature of their disease. Even in advanced cases, parents may not be
      aware of severe visual impairment until the development of externally visible
      changes such as band keratopathy, strabismus, or leukocoria. Therefore, the
      diagnosis is often delayed and severe complications may be seen at the time of
      initial visit. Young children may not be cooperative for a complete ocular
      examination and subtle findings of intraocular inflammation such as trace cells
      may be easily missed in the early stages of the disease. Children, in general,
      tend to have more severe and chronic intraocular inflammation that frequently
      results in ocular complications and visual loss. In children who present with
      amblyopia or strabismus, a careful examination is required to rule out uveitis as
      an underlying cause. Delayed and variable presentations cause a distinct
      challenge in the diagnosis of uveitis in children, furthermore differential
      diagnosis also requires awareness of etiologies which are different from adults.
      There are unique forms of uveitis and masquerade syndromes in this age group,
      while some entities commonly encountered in adults are rare in children.

PMID- 22454750
TI  - Myopia and inflammation.
AB  - The correlation between myopia and intraocular inflammation has rarely been
      explored. The aim of this article is to review myopic changes induced by
      inflammatory diseases and inflammatory diseases related to myopia, followed by a
      discussion on inflammatory choroidal neovascularization. Clinical cases are used
      to illustrate these conditions. The review does not include inflammatory
      conditions caused by surgical interventions employed for treatment of myopia.
      Uveitic conditions that can induce a myopic shift include sclero-choroidal
      inflammation, lens induced myopia due to steroid cataracts, juvenile idiopathic
      arthritis (JIA) induced myopia, and transient drug induced myopia due to
      sulfonamides and acetazolamide used for treatment of ocular toxoplasmosis and
      inflammatory cystoid macular edema, respectively. Most inflammatory conditions
      related to myopia are conditions involving the choriocapillaris. These include
      multifocal choroiditis and/or punctate inner choroiditis, multiple evanescent
      white dot syndrome and acute idiopathic blind spot enlargement. It can be
      hypothesized that fragility of the choriocapillaris due to particular anatomic
      changes due to myopia, together with unknown immunogenetic factors predispose
      myopic eyes to primary inflammatory choriocapillaropathies.

PMID- 22454751
TI  - CNS diseases and uveitis.
AB  - A number of inflammatory, infectious, neoplastic and idiopathic disorders affect
      the eye and the central nervous system (CNS) concurrently or at different time
      frames. These conditions pose a diagnostic challenge to the clinician since they
      may present with similar ocular and neurological manifestations. The purpose of
      this review is to describe major neurological syndromes including multiple
      sclerosis, Vogt-Koyanagi-Harada disease, other autoimmune syndromes, and several
      infectious diseases which may affect the eye. This article may serve as a guide
      for the diagnosis and treatment of such disorders. It should be noted that these
      conditions have been viewed from a neurologist's perspective thereby neurologic
      involvement is stressed.

PMID- 22454752
TI  - Biologic agents in inflammatory eye disease.
AB  - Non-infectious uveitis is a potentially sight threatening disease. Along the
      years, several therapeutic strategies have been proposed as a means to its
      treatment, including local and systemic steroids, immunosuppressives and more
      recently, biologic agents. The introduction of biologics can be defined as a new
      era: biologic therapies provide new options for patients with refractory and
      sight threatening inflammatory disorders. The availability of such novel
      treatment modalities has markedly improved the therapy of uveitis and
      considerably increased the possibility of long-term remissions. This article
      provides a review of current literature on biologic agents, such as tumor
      necrosis factor blockers, anti-interleukins and other related biologics, such as
      interferon alpha, for the treatment of uveitis. Several reports describe the
      efficacy of biologics in controlling a large number of refractory uveitides,
      suggesting a central role in managing ocular inflammatory diseases. However,
      there is still lack of randomized controlled trials to validate most of their
      applications. Biologics are promising drugs for the treatment of uveitis, showing
      a favorable safety and efficacy profile. On the other hand, lack of evidence from
      randomized controlled studies limits our understanding as to when commence
      treatment, which agent to choose, and how long to continue therapy. In addition,
      high cost and the potential for serious and unpredictable complications have very
      often limited their use in uveitis refractory to traditional immunosuppressive
      therapy.

PMID- 22454753
TI  - Sustained release intraocular drug delivery devices for treatment of uveitis.
AB  - Corticosteroids have been the mainstay of uveitis therapy. When intraocular
      inflammation is unresponsive to steroids, or steroid related side effects become
      a concern, steroid-sparing medications may be administered which can be
      classified into immunosuppressive and immunomodulatory agents. Uveitis treatment
      can be delivered systemically, topically, periocularly or intraocularly. All of
      the above mentioned medications can entail significant systemic side effects,
      particularly if administered for prolonged durations, which may become treatment
      limiting. Some medications, particularly hydrophobic compounds, may poorly cross
      the blood-retinal barrier. Topical medications, which have the least side
      effects, do not penetrate well into the posterior segment and are unsuitable for
      posterior uveitis which is often sight-threatening. Intraocular or periocular
      injections can deliver relatively high doses of drug to the eye with few or no
      systemic side effects. However, such injections are associated with significant
      complications and must often be repeated at regular intervals. Compliance with
      any form of regular medication can be a problem, particularly if its
      administration is associated with discomfort or if side effects are unpleasant.
      To overcome the above-mentioned limitations, an increasing number of sustained
      release drug delivery devices using different mechanisms and containing a variety
      of agents have been developed to treat uveitis. This review discusses various
      current and future sustained-release ophthalmic drug delivery systems for
      treatment of uveitis.

PMID- 22454754
TI  - Idiopathic retinal vasculitis, aneurysms and neuroretinitis syndrome associated
      with positive perinuclear antineutrophil cytoplasmic antibody.
AB  - PURPOSE: To report a case of idiopathic retinal vasculitis, aneurysms and
      neuroretinitis (IRVAN) syndrome associated with positive perinuclear
      antineutrophil cytoplasmic antibody (P-ANCA). CASE REPORT: A 51-year-old man
      presented with loss of vision in his right eye since many years ago and blurred
      vision in his left eye over the past year. Ophthalmologic examination revealed
      optic atrophy and old vascular sheathing in the right eye and blurred disc
      margin, macular exudation, flame shaped hemorrhages, retinal vascular sheathing
      and multiple aneurysms at arterial bifurcation sites in the left eye, findings
      compatible with IRVAN syndrome. On systemic workup, the only notable finding was
      P-ANCA positivity. CONCLUSION: IRVAN syndrome may be a retinal component of P
      ANCA associated vasculitis.

PMID- 22454755
TI  - Central serous chorioretinopathy mistaken for tuberculous choroiditis.
AB  - PURPOSE: To report a patient erroneously diagnosed with tuberculous choroiditis
      who was accordingly treated with long term steroids which in turn, worsened the
      actual disease process that turned out to be central serous chorioretinopathy
      (CSC). CASE REPORT: A 59-year-old Caucasian man developed a chorioretinal disease
      in his right eye in 1997. Having a positive tuberculin skin test, tuberculous
      chorioretinitis was suspected and antituberculous therapy was administered for 4
      months. In 2005, visual symptoms in the same eye recurred and despite negative
      interferon gamma release assay, tuberculous choroiditis was considered as the
      diagnosis and the patient further received massive corticosteroid therapy along
      with antituberculous agents. Despite a deteriorating clinical picture, therapy
      was continued. Upon initial examination at our center, no sign of inflammation
      was observed and a diagnosis of CSC was made, consequently steroid therapy was
      terminated. CONCLUSION: In some chorioretinopathies, it is difficult to
      differentiate inflammatory from non-inflammatory causes. One should observe the
      course of the disease and question the initial diagnosis when no improvement or
      deterioration occurs despite therapy.

PMID- 22454756
TI  - Acute posterior multifocal placoid pigment epitheliopathy as the initial
      manifestation of sarcoidosis.
AB  - PURPOSE: To report an undiagnosed case of systemic sarcoidosis manifesting with
      bilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE).
      CASE REPORT: A 26-year-old Caucasian man was referred for management of
      unilateral visual loss together with a paracentral scotoma developing 2 weeks
      after a flu-like syndrome. Clinical signs and ancillary diagnostic investigations
      suggested APMPPE. Laboratory tests demonstrated elevated serum angiotensin
      converting enzyme and lysozyme levels. Chest CT-scan disclosed moderate hilar
      lymph node calcifications but QuantiFERON-TB gold test was negative and
      bronchoalveolar lavage and biopsies were unremarkable. Accessory salivary gland
      biopsy disclosed epithelioid and gigantocellular granuloma formation without
      caseum, confirming a diagnosis of sarcoidosis. The fellow eye was involved a few
      days later and the patient complained of dyspnea. Echocardiography disclosed
      severe granulomatous myocardial infiltration and high dose corticosteroids and
      intravenous cyclophosphamide were initiated. Systemic treatment controlled both
      cardiac and ocular lesions, and was tapered accordingly. CONCLUSION: The
      constellation of "white dot syndromes" and systemic symptoms necessitates a
      general work-up to exclude granulomatous disorders such as sarcoidosis or
      tuberculosis. Delayed diagnosis of cardiac sarcoidosis may have life-threatening
      consequences and the ophthalmologist may be the first physician to diagnose the
      condition.

PMID- 22454757
TI  - Bilateral primary intraocular lymphoma.
AB  - PURPOSE: To report a case of bilateral primary intraocular lymphoma. CASE REPORT:
      A 33-year-old man presented with bilateral blurred vision since two years ago.
      Examination revealed large keratic precipitates, anterior chamber reaction,
      posterior subcapsular cataracts, and vitreous infiltration. After a short trial
      of topical and periocular steroids, diagnostic 25-gauge pars plana vitrectomy was
      performed and cytologic evaluation of the aspirate confirmed a diagnosis of
      intraocular lymphoma. The patient was subsequently managed with intravitreal
      methotrexate in both eyes and responded favorably. Central nervous system workup
      for lymphoma was negative. CONCLUSION: Primary intraocular lymphoma should be
      considered in young adults suffering from chronic recalcitrant panuveitis.

PMID- 22454758
TI  - Multifocal choroiditis in a diabetic patient.

PMID- 22454759
TI  - Introducing polyautoimmunity: secondary autoimmune diseases no longer exist.
AB  - Similar pathophysiological mechanisms within autoimmune diseases have stimulated
      searches for common genetic roots. Polyautoimmunity is defined as the presence of
      more than one autoimmune disease in a single patient. When three or more
      autoimmune diseases coexist, this condition is called multiple autoimmune
      syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients
      belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in
      373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjogren's syndrome
      (SS) were the most frequent diseases encountered. Factors significantly
      associated with polyautoimmunity were female gender and familial autoimmunity.
      Through a systematic literature review, an updated search was done for all MAS
      cases (January 2006-September 2011). There were 142 articles retrieved
      corresponding to 226 cases. Next, we performed a clustering analysis in which
      AITD followed by systemic lupus erythematosus and SS were the most hierarchical
      diseases encountered. Our results indicate that coexistence of autoimmune
      diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the
      term proposed for this association of disorders, which encompasses the concept of
      a common origin for these diseases.

PMID- 22454760
TI  - Significant changes in the levels of secreted cytokines in brains of experimental
      antiphospholipid syndrome mice.
AB  - Antiphospholipid syndrome (APS) is characterized by thromboses and
      neuropsychiatric manifestations possibly linked to brain inflammation. In order
      to examine the levels of proinflammatory and anti-inflammatory cytokines in
      experimental APS (eAPS) mice brains, we measured the levels of TNF-alpha, IFN
      gamma, and IL-10 in brain homogenates (cytosolic fractions) and in brain slices
      (secreted level) at 6, 15, and 24 weeks after immunization. We induced eAPS by
      immunization of Balb/c mice with beta(2)-glycoprotein I (beta(2)GPI), the major
      autoantigen in the disease and controls with adjuvant alone. We found increased
      levels of secreted TNF-alpha in eAPS mice for the entire experiment period.
      Cytosolic and secreted IL-10 and IFN-gamma levels in eAPS mice were lower at 6
      and 15 weeks and higher at 24 weeks after immunization. The results suggest that
      brain disease in APS is associated with significant and complex changes in
      proinflammatory and anti-inflammatory cytokines.

PMID- 22454761
TI  - Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via
      Crossreactivity or Molecular Mimicry.
AB  - A general consensus supports fundamental roles for both genetic and
      environmental, mainly microbial, factors in the development of autoimmune
      diseases. One form of autoimmune rheumatic diseases is confined to a group of
      nonpyogenic conditions which are usually preceded by or associated with either
      explicit or occult infections. A previous history of clinical pharyngitis,
      gastroenteritis/urethritis, or tick-borne skin manifestation can be obtained from
      patients with rheumatic fever, reactive arthritis, or Lyme disease, respectively,
      whilst, other rheumatic diseases like rheumatoid arthritis (RA), ankylosing
      spondylitis (AS), and Crohn's disease (CD) are usually lacking such an
      association with a noticeable microbial infection. A great amount of data
      supports the notion that RA is most likely caused by Proteus asymptomatic urinary
      tract infections, whilst AS and CD are caused by subclinical bowel infections
      with Klebsiella microbes. Molecular mimicry is the main pathogenetic mechanism
      that can explain these forms of microbe-disease associations, where the causative
      microbes can initiate the disease with consequent productions of antibacterial
      and crossreactive autoantibodies which have a great impact in the propagation and
      the development of these diseases.

PMID- 22454762
TI  - Effect of Food on the Steady-State Pharmacokinetics of Tenofovir and
      Emtricitabine plus Efavirenz in Ugandan Adults.
AB  - We investigated the effect of food on the steady-state pharmacokinetics of a
      proprietary fixed-dose combination (FDC) tablet containing tenofovir disoproxil
      fumarate (TDF)/emtricitabine/efavirenz. Fifteen Ugandan HIV-1 patients at steady
      state dosing with TDF/emtricitabine/efavirenz were admitted for 24-hour intensive
      pharmacokinetic sampling after dosing in the fasting state. Blood sampling was
      repeated seven days later with TDF/emtricitabine/efavirenz administered with food
      (19 g fat). Drug concentrations in plasma were determined by liquid
      chromatography and tandem mass spectrometry. Geometric mean ratios (GMRs) and
      confidence intervals (CIs) of parameters were calculated (reference, fasting).
      For efavirenz, GMRs (90% CIs) for C(max), AUC(0-24), and C(24) were 1.47 (1.24
      1.75), 1.13 (1.03-1.23), and 1.01 (0.91-1.11), respectively. Corresponding GMRs
      were 1.04 (0.84-1.27), 1.19 (1.10-1.29), and 0.99 (0.82-1.19) for tenofovir, 0.83
      (0.76-0.92), 0.87 (0.78-0.97), and 0.91 (0.73-1.14) for emtricitabine. Stable
      patients may take the FDC without meal restrictions. The FDC should be taken
      without food by patients experiencing central nervous system toxicities.

PMID- 22454763
TI  - Intra-abdominal hypertension and abdominal compartment syndrome in association
      with ruptured abdominal aortic aneurysm in the endovascular era: vigilance
      remains critical.
AB  - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are
      common complications of ruptured abdominal aortoiliac aneurysms (rAAAs) and other
      abdominal vascular catastrophes even in the age of endovascular therapy.
      Morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and
      multiple organ failure (MOF) are significant. Recognition and management of IAH
      are key critical care measures which may decrease morbidity and improve survival
      in these vascular patients. Two strategies have been utilized: expectant
      management with prompt decompressive laparotomy upon diagnosis of threshold
      levels of IAH versus prophylactic, delayed abdominal closure based upon clinical
      parameters at the time of initial repair. Competent management of the abdominal
      wound with preservation of abdominal domain is also an important component of the
      care of these patients. In this review, we describe published experience with IAH
      and ACS complicating abdominal vascular catastrophes, experience with ACS
      complicating endovascular repair of rAAAs, and techniques for management of the
      abdominal wound. Vigilance and appropriate management of IAH and ACS remains
      critically important in decreasing morbidity and optimizing survival following
      catastrophic intra-abdominal vascular events.

PMID- 22454764
TI  - The impact of a pulmonary-artery-catheter-based protocol on fluid and
      catecholamine administration in early sepsis.
AB  - Objective. The pulmonary artery catheter (PAC) remains topic of debate. Despite
      abundant data, it is of note that many trials did not incorporate a treatment
      protocol. Methods. We retrospectively evaluated fluid balances and catecholamine
      doses in septic patients after the introduction of a PAC-based treatment protocol
      in comparison to historic controls. Results. 2 * 70 patients were included. The
      first day the PAC group had a significantly higher positive fluid balance in
      comparison to controls (6.1 +/- 2.6 versus 3.8 +/- 2.4 litre, P < 0.001). After 7
      days the cumulative fluid balance in the PAC group was significantly lower than
      in controls (9.4 +/- 7.4 versus 13 +/- 7.6 litre, P = 0.001). Maximum dose of
      norepinephrine was significantly higher in the PAC group. Compared to controls
      this was associated with a significant reduction in ventilator and ICU days.
      Conclusions. Introduction of a PAC-based treatment protocol in sepsis changed the
      administration of fluid and vasopressors significantly.

PMID- 22454765
TI  - A Novel Method (CiMON) for Continuous Intra-Abdominal Pressure Monitoring: Pilot
      Test in a Pig Model.
AB  - Background. Intravesical pressure (IAP(ivp)) measurement is considered to be the
      gold standard for assessment of intra-abdominal pressure (IAP). This study
      evaluated a new minimally invasive IAP monitoring device (CiMON) against three
      other devices in a wide range of clinically relevant IAP and in different body
      positions in healthy pigs. Methods. The CiMON catheter (IAP(CiM)) and another
      balloon-tipped catheter (IAP(spie)) were positioned into the stomach. Fluid
      filled catheters were used for direct intraperitoneal (IAP(dir)) and IAP(ivp)
      measurement. Both in supine and 25 degrees  head-of-bed positions, IAP was
      increased from baseline to 30 mmHg. At every IAP level, 4 IAP measurements were
      recorded simultaneously. Mean differences and the limits of agreement were
      calculated. Results. Bias between IAP(CiM) and IAP(spie) was nearly zero with
      very good agreement, both in supine and 25 degrees  position. In supine position,
      IAP(CiM) slightly overestimated IAP(ivp) and IAP(dir) by 1.5 and 2.1 mmHg with
      reasonable agreement. In 25 degrees  position, IAP(CiM) underestimated IAP(ivp)
      and IAP(dir) by 1.0 and 0.5 mmHg, again with reasonable agreement. Conclusions.
      Agreement between IAP(CiM) and IAP(spie) was very good, while good-to-moderate
      agreement exists between IAP(CiM) and IAP(dir) or IAP(ivp). Simplicity,
      continuous monitoring, and the combination with a feeding tube should lead to
      further clinical studies, evaluating this new CiMON device.

PMID- 22454766
TI  - Consecutive daily measurements of luminal concentrations of lactate in the rectum
      in septic shock patients.
AB  - In a recent study we found no difference in the concentrations of luminal lactate
      in the rectum between nonsurvivors and survivors in early septic shock (<24 h).
      This study was initiated to investigate if there are any changes in the
      concentrations of luminal lactate in the rectum during the first 3 days of septic
      shock and possible differences between nonsurvivors and survivors. Methods. We
      studied 22 patients with septic shock in this observational study. Six to 24 h
      after the onset of septic shock the concentration of lactate in the rectal lumen
      was estimated by 4 h equilibrium dialysis (day 1). The rectal dialysis was
      repeated on day 2 and day 3. Results. The concentration of lactate in the rectal
      lumen did not change over the 3 days in neither nonsurvivors nor survivors.
      Rectal luminal and arterial lactate concentrations were not different.
      Conclusion. There was no change in the concentration of lactate in the rectal
      lumen over time in patients with septic shock. Also, there was no difference
      between nonsurvivors and survivors.

PMID- 22454767
TI  - Relationship between Abdominal Pressure, Pulmonary Compliance, and Cardiac
      Preload in a Porcine Model.
AB  - Rationale. Elevated intra-abdominal pressure (IAP) may compromise respiratory and
      cardiovascular function by abdomino-thoracic pressure transmission. We aimed (1)
      to study the effects of elevated IAP on pleural pressure, (2) to understand the
      implications for lung and chest wall compliances and (3) to determine whether
      volumetric filling parameters may be more accurate than classical pressure-based
      filling pressures for preload assessment in the setting of elevated IAP. Methods.
      In eleven pigs, IAP was increased stepwise from 6 to 30 mmHg. Hemodynamic,
      esophageal, and pulmonary pressures were recorded. Results. 17% (end-expiratory)
      to 62% (end-inspiratory) of elevated IAP was transmitted to the thoracic
      compartment. Respiratory system compliance decreased significantly with elevated
      IAP and chest wall compliance decreased. Central venous and pulmonary wedge
      pressure increased with increasing IAP and correlated inversely (r = -0.31) with
      stroke index (SI). Global end-diastolic volume index was unaffected by IAP and
      correlated best with SI (r = 0.52). Conclusions. Increased IAP is transferred to
      the thoracic compartment and results in a decreased respiratory system compliance
      due to decreased chest wall compliance. Volumetric filling parameters and
      transmural filling pressures are clearly superior to classical cardiac filling
      pressures in the assessment of cardiac preload during elevated IAP.

PMID- 22454768
TI  - Pathways to prevention for children of depressed mothers: a review of the
      literature and recommendations for practice.
AB  - Maternal depression is one of the most well-documented risk factors for child and
      adolescent depression, but little work has focused on how to reduce this risk.
      Although a few interventions have been developed and tested, implementing
      targeted prevention efforts with depressed mothers and their children is not
      common practice. The increased risk of depression for children of depressed
      mothers is so clear, however, professionals can no longer "sit on the sidelines"
      without initiating specific prevention efforts with this population. To do so
      requires a paradigm shift-moving from a focus on individual treatment to a
      prevention approach that engages the entire family as the unit of care. The
      purpose of this paper is to draw on existing literature to highlight potential
      "pathways to prevention" for children of depressed mothers. Recommendations for
      initiating these pathways based on family lifecycle stage, point of contact, and
      service setting are presented and discussed.

PMID- 22454769
TI  - Gender Differences in Depression: Assessing Mediational Effects of Overt
      Behaviors and Environmental Reward through Daily Diary Monitoring.
AB  - Gender differences in the prevalence of depression are well documented. To
      further explore the relation between gender and depression, this study used daily
      diaries to examine gender differences within thirteen behavioral domains and
      whether differential frequency of overt behaviors and environmental reward
      mediated the relationship between gender and depression severity. The sample
      included 82 undergraduate students [66% females; 84% Caucasian; Mean age = 20.2
      years]. Overall, females engaged in a significantly greater breadth of behavioral
      domains and reported a higher level of environmental reward. Females spent more
      time in the domains of health/hygiene, spiritual activities, and eating with
      others. Males spent more time in the domains of physical activity, sexual
      activity, and hobbies and recreational experiences. Females found social
      activities, passive/sedentary behaviors, eating with others, and engagement in
      "other" activities more rewarding. Gender had a significant direct effect on
      depression severity, with females reporting increased depression. This effect was
      attenuated by the mediator (total environmental reward) such that to the extent
      females exhibited increased environmental reward, the gender effect on depression
      was attenuated. These data support behavioral models of depression, indicate
      increased reinforcement sensitivity among females, and have clinical relevance in
      the context of assessment and behavioral activation interventions for depression.

PMID- 22454770
TI  - Neuroticism in young women with fibromyalgia links to key clinical features.
AB  - Objective. We examined personality traits in young women with FM, in order to
      seek associations with key psychological processes and clinical symptoms.
      Methods. Twenty-seven women with FM and 29 age-matched female healthy controls
      [HC] completed a series of questionnaires examining FM symptoms, personality and
      psychological variables. Results. Significant differences between characteristic
      FM symptoms (sleep, pain, fatigue, and confusion) as well as for the
      psychological variables of depression, anxiety, and stress were found between FM
      and HC (P < 0.001). Neuroticism was the only subscale of the Big Five Inventory
      that showed a significant difference between the FM group and HC group [P <
      0.05]. Within the FM group, there was a significant association between the level
      of the neuroticism and each of pain, sleep, fatigue, and confusion, depression,
      anxiety, and stress (P < 0.05-0.01). The association between the level of
      neuroticism and the level of stress was the strongest of all variables tested (P
      < 0.001). Conclusion. The personality trait of neuroticism significantly
      associates with the key FM characteristics of pain, sleep, fatigue and confusion
      as well as the common co-morbidities of depression, anxiety and stress.
      Personality appears to be an important modulator of FM clinical symptoms.

PMID- 22454772
TI  - Emergency department crowding: time for interventions and policy evaluations.
AB  - This paper summarises the consequences of emergency department crowding. It
      provides a comparison of the scales used to measure emergency department
      crowding. We discuss the multiple causes of crowding and present an up-to-date
      literature review of the interventions that reduce the adverse consequences of
      crowding. We consider interventions at the level of an individual hospital and a
      policy level.

PMID- 22454773
TI  - Patients refusing prehospital transport are increasingly likely to be geriatric.
AB  - Objective. Elderly patients are becoming an increasingly larger proportion of our
      population, and there is a paucity of data regarding the epidemiology of
      geriatric patients refusing transport. Treatment refusal rates range from 5% to
      15% in many studies. This study sought to test the hypothesis that geriatric
      patients constituted an increasing proportion of those persons refusing
      prehospital transport. Methods. This study was a retrospective analysis of data
      from a query of a large urban EMS service. Results. There were a total of 22,347
      adult transport refusals recorded during the 16-month study period. Multivariate
      logistic regression incorporating covariates for sex, race, season, chief
      complaint, metropolitan region, and whether any treatment occurred prior to
      transport refusal confirmed the increasing likelihood of Period 2 patients being
      geriatric, as compared with Period 1 (OR 1.24, 95% CI 1.14-1.35, Wald P < .001).
      Conclusion. This data shows that despite controlling for these covariates,
      patients refusing transport in the second period of this study were nearly 25%
      more likely to be geriatric as compared to those in the initial 8 months of the
      study.

PMID- 22454771
TI  - Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor
      Progression and Wound Repair: Functional Interactions between the Serine Protease
      and Matrix Metalloproteinase Cascades.
AB  - Spatial and temporal regulation of the pericellular proteolytic environment by
      local growth factors, such as EGF and TGF-beta, initiates a wide repertoire of
      cellular responses coupled to a plasmin/matrix metalloproteinase (MMP) dependent
      stromal-remodeling axis. Cell motility and invasion, tumor metastasis, wound
      healing, and organ fibrosis, for example, represent diverse events controlled by
      expression of a subset of genes that encode various classes of tissue remodeling
      proteins. These include members of the serine protease and MMP families that
      functionally constitute a complex system of interacting protease cascades and
      titrated by their respective inhibitors. Several structural components of the
      extracellular matrix are upregulated by TGF-beta as are matrix-active proteases
      (e.g., urokinase (uPA), plasmin, MMP-1, -3, -9, -10, -11, -13, -14). Stringent
      controls on serine protease/MMP expression and their topographic activity are
      essential for maintaining tissue homeostasis. Targeting individual elements in
      this highly interactive network may lead to novel therapeutic approaches for the
      treatment of cancer, fibrotic diseases, and chronic wounds.

PMID- 22454774
TI  - Parent and Patient Satisfaction after Treatment for Supracondylar Humerus
      Fractures in 139 Children: No Difference between Skeletal Traction and Crossed
      Pin Fixation at Long-Term Followup.
AB  - Aim. The aim of this study was to see whether the benefits of crossed wire
      fixation over skeletal traction in the treatment of pediatric supracondylar
      humerus fractures (SCHF) were mirrored in the children's or their caregivers'
      rating of the experience. Methods. As part of a study of the clinical outcome of
      SCHF, all the patients and the parents were asked to rate their experience of the
      treatment on a visual analogue scale (VAS). Results. There was no difference in
      the patients' or the parents' experience between the treatment groups. However
      there was a difference between the parents with children who experienced a
      neurovascular complication (mean VAS 6.1) and those that did not (mean VAS 4.3, P
      = 0.03). The boys rated the experience as less negative (mean VAS 3.6) than the
      girls (mean VAS 4.7, P = 0.02). Conclusion. In the long term, avoiding
      complications was more important to the parents than the choice of treatment for
      SCHF in the children.

PMID- 22454775
TI  - Toll-like receptors in ischaemia and its potential role in the pathophysiology of
      muscle damage in critical limb ischaemia.
AB  - Toll-like receptors (TLRs) are key receptors of the innate immune system which
      are expressed on immune and nonimmune cells. They are activated by both pathogen
      associated molecular patterns and endogenous ligands. Activation of TLRs
      culminates in the release of proinflammatory cytokines, chemokines, and
      apoptosis. Ischaemia and ischaemia/reperfusion (I/R) injury are associated with
      significant inflammation and tissue damage. There is emerging evidence to suggest
      that TLRs are involved in mediating ischaemia-induced damage in several organs.
      Critical limb ischaemia (CLI) is the most severe form of peripheral arterial
      disease (PAD) and is associated with skeletal muscle damage and tissue loss;
      however its pathophysiology is poorly understood. This paper will underline the
      evidence implicating TLRs in the pathophysiology of cerebral, renal, hepatic,
      myocardial, and skeletal muscle ischaemia and I/R injury and discuss preliminary
      data that alludes to the potential role of TLRs in the pathophysiology of
      skeletal muscle damage in CLI.

PMID- 22454776
TI  - The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular
      Disease.
AB  - Cardiovascular disease is the leading cause of death. The disease is due to
      atherosclerosis which is characterized by lipid and fat accumulation in arterial
      blood vessel walls. A key causative event is the accumulation of oxidised low
      density lipoprotein particles within vascular cells, and this is mediated by
      scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is
      expressed on endothelial, vascular smooth muscle, and lymphoid cells including
      macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis.
      LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization
      pathway. Transgenic animal model studies show that LOX-1 plays a significant role
      in atherosclerotic plaque initiation and progression. Administration of LOX-1
      antibodies in cellular and animal models suggest that such intervention inhibits
      atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene
      therapy or small molecule inhibitors would be new ways to address the increasing
      incidence of vascular disease in many countries.

PMID- 22454777
TI  - Appreciating the strengths and weaknesses of transthoracic echocardiography in
      hemodynamic assessments.
AB  - Transthoracic echocardiography (TTE) is becoming the choice of hemodynamic
      assessment tool in many intensive care units. With an ever increasing number of
      training programs available worldwide, learning the skills to perform TTE is no
      longer a limiting factor. Instead, the future emphasis will be shifted to teach
      the users how to recognize measurement errors and artefacts (internal validity),
      to realize the limitations of TTE in various applications, and finally how to
      apply the information to the patient in question (external validity). This paper
      aims to achieve these objectives in a common area of TTE application-hemodynamic
      assessments. We explore the strengths and weaknesses of TTE in such assessments
      in this paper. Various methods of hemodynamic assessments, such as cardiac output
      measurements, estimation of preload, and assessment of fluid responsiveness, will
      be discussed.

PMID- 22454778
TI  - Safety and efficacy of mechanical thrombectomy with solitaire stent retrieval for
      acute ischemic stroke: a systematic review.
AB  - PURPOSE: In recent years, mechanical thrombectomy using Solitaire stent retrieval
      has been tried for treating acute ischemic stroke with a large artery occlusion.
      We systematically reviewed published articles to appraise the evidence that
      supports the safety and efficacy of the mechanical thrombectomy in acute strokes
      with Solitaire stent. MATERIALS AND METHODS: Systematic searches using Medline
      and Scopus were performed for studies evaluating mechanical thrombectomy using a
      Solitaire stent in acute ischemic stroke. Articles were included if they were
      published since 2008, contained at least 5 subjects, and provided clinical
      results. RESULTS: Thirteen articles (262 cases) were included in this review. The
      mean time of the procedures ranged from 37 to 95.6 minutes in 10 studies. The
      success of recanalization was achieved in 89.7% and the recanalization rate
      varied from 66.7% to 100% in all 13 studies. The overall rates of the symptomatic
      hemorrhagic complications and mortality were 6.8% and 11.1%, respectively. A
      favorable outcome of mRS 2 or under was 47.3%. Procedure-induced complications
      developed in 3.4%. CONCLUSION: The present review suggested that mechanical
      thrombectomy using a Solitaire stent in acute ischemic stroke was effective in
      recanalizing the occluded artery. The rate of procedural complications was small.

PMID- 22454779
TI  - Angioarchitecture of Spinal Dural Arteriovenous Fistula - Evaluation with 3D
      Rotational Angiography.
AB  - PURPOSE: The complex angioarchitecture of spinal dural arteriovenous fistulas
      (SDAVFs) sometimes preclude angiographic analyses or superselective procedures.
      Therefore, the effectiveness of 3 dimensional rotational angiography (3DRA) as a
      detailed imaging technique for SDAVFs was evaluated. MATERIALS AND METHODS: Of 57
      patients with spinal vascular malformations, recent 13 SDAVF patients underwent
      3DRA. The advantage of 3DRA compared to digital subtraction angiography (DSA) in
      imaging SDAVF was assessed. Angioarchitecture of SDAVF was focused on location,
      number, and course of feeders and draining vein. Appropriate angled views were
      also selected to reveal the segmental artery and feeders. RESULTS: 3DRA technique
      provided additional information for imaging evaluation of SDAVFs compared to DSA;
      the presence of multiple feeders, including their transdural portions, as well as
      their courses. The contralaterally angled anterior-oblique-caudal (spider) view
      showed the radicular feeder by separating the intercostal artery and the dorsal
      muscular branch. The bottom-to-up (tunnel) view was useful for revealing the
      location (ventral vs. dorsal) including sharp medial turn of the dural feeder.
      The dual mode, which displays both vessels and bones, revealed the course of the
      feeders and the fistula related to the spinal bony column. CONCLUSION: Because
      spinal vasculature overlaps in DSA, 3DRA revealed additional information for
      evaluations of the number and transdural course of fistular feeders in SDAVFs,
      and it offers working angles to obtain appropriate views.

PMID- 22454780
TI  - Outpatient (Same-day care) Neuroangiography and Neurointervention.
AB  - PURPOSE: There have been few reports regarding same-day discharge following
      uncomplicated procedures such as cerebral angiography and neurointervention. We
      present same-day experience with cerebral angiography and neurointervention
      during the past three years. MATERIALS AND METHODS: Four hundred and fifty-three
      patients underwent cerebral angiography or neurointervention at Asan Medical
      Center between January 2009 and December 2011. Of these patients, 249 (55%)
      underwent diagnostic catheter cerebral angiography and 204 patients (45%)
      underwent neurointerventional procedures as same-day procedures. We analyzed any
      complications, the modified patient-care process, the yearly trend in patient
      increases, disease categories, and the additional duration of admission for these
      procedures. RESULTS: The number of overall patients increased by an average of
      51% annually. The disease categories included aneurysm (51%), atherosclerosis
      (11%) and arteriovenous malformation (10%), etc. for which the patient underwent
      angiography, and aneurysm (42%), venous malformation (28%), and arteriovenous
      malformation (17%), etc. for which patients underwent neurointervention. Same-day
      care patients were admitted to the intermediary care unit in the angiosuite.
      Neurointervention patients were sent to the neurology intensive unit after the
      procedure. The same-day care patients stayed in angiosuite for six hours
      following the transfemoral procedure. The mean admission duration for
      neurointervention was 2.4 days. There were no reported complications for the same
      day care procedures. CONCLUSION: Our study revealed an increasing tendency toward
      same-day care for patients who require angiography and neurointervention. Further
      studies will be required to better define the cost-minimization effects of
      outpatient practice as well as the patient perception of this fast-tracking
      method. We propose that outpatient angiography and neurointervention will
      undoubtedly continue to increase over the next decade.

PMID- 22454781
TI  - Change of Platelet Reactivity to Antiplatelet Therapy after Stenting Procedure
      for Cerebral Artery Stenosis: VerifyNow Antiplatelet Assay before and after
      Stenting.
AB  - PURPOSE: VerifyNow antiplatelet assays were performed before and after stenting
      for various cerebral artery stenoses to determine the effect of the procedure
      itself to the function of dual antiplatelets given. MATERIALS AND METHODS: A
      total of 30 consecutive patients underwent cerebral arterial stenting procedure
      were enrolled. The antiplatelet pretreatment regimen was aspirin (100 mg daily)
      and clopidogrel (300 mg of loading dose followed by 75mg daily). VerifyNow
      antiplatelet assay performed before and right after stenting. The two test
      results were compared in terms of aspirin-reaction unit (ARU), P2Y12 reaction
      units (PRU), baseline (BASE), and percentage inhibition. We evaluated occurrence
      of any intra-procedural in-stent thrombosis or immediate thromboembolic
      complication, and ischemic events in 1-month follow-up. RESULTS: The median Pre
      ARU was 418 (range, 350-586). For clopidogrel the medians of the pre-BASE, PRU,
      and percent inhibition were 338 (279-454), 256 (56-325), and 27% (0-57%). The
      medians of the post-ARU, BASE, PRU, and percent inhibition after stenting were
      469 (range, 389-573), 378 (288-453), 274 (81-370), and 26% (0-79%). There was a
      significant increase of ARU (p=0.045), BASE (p=0.026), and PRU (p=0.018) before
      and after stenting. One immediate thromboembolic event was observed in poor
      response group after stenting. There was no in-stent thrombosis and ischemic
      event in 1-month follow-up. CONCLUSION: We observed a significant increase of
      platelet reactivity to dual antiplatelet therapy right after stenting procedure
      for various cerebral arterial stenoses.

PMID- 22454782
TI  - Usefulness of stent implantation for treatment of intracranial atherosclerotic
      stenoses.
AB  - PURPOSE: We evaluated the usefulness of intracranial stent implantation for
      treating patients with atherosclerotic stenosis and with recurrent, ischemic,
      neurological symptoms despite having undergone medical therapy. MATERIALS AND
      METHODS: Between March 2004 and April 2010, we attempted intracranial, stent
      assisted angioplasty in 77 patients with 85 lesions (anterior circulation 73
      cases, posterior circulation 12 cases) and who had ischemic neurological symptoms
      with more than 50% major cerebral artery stenosis. We analyzed the results
      regarding the technical success rate, complication rate, and restenosis rate
      during the mean 29.4 month follow-up period. RESULTS: Intracranial stent
      implantation was successfully performed in 74 cases (87.1%). In nine cases among
      the 11, failed cases, stent implantation failure was due to the tortuosity of the
      target vessel. One patient experienced middle cerebral artery rupture during the
      procedure, and we embolized the vessel using a microcoil. Five patients developed
      cerebral infarction in three weeks after the procedure, three of whom improved
      using conservative management, although the other, two patients expired. The mean
      number of residual stenoses decreased from 72.3% to 14.7%. Three patients
      demonstrated significant in-stent restenosis, i.e. more than 50%, during the
      follow-up period. CONCLUSION: As stent-assisted angioplasty in intracranial,
      atherosclerotic stenosis is effective and relatively safe, it can be considered
      as an alternative treatment for patients with recurrent, ischemic, neurologic
      symptoms despite having undergone medical therapy.

PMID- 22454783
TI  - Initial Experience with Neuroform EZ in the Treatment of Wide-neck Cerebral
      Aneurysms.
AB  - PURPOSE: Stent-assisted coiling allows embolization and parent vessel
      reconstruction of wide-necked intracranial aneurysms. The Neuroform EZ (Boston
      Scientific, Fremont, CA, U.S.A.) stent delivery system offers deployment of a
      Neuroform stent with fewer steps and improved operator control. Initial
      experience, technical considerations, and treatment outcomes using the Neuroform
      EZ stent delivery system in combination with coil embolization are reported.
      MATERIALS AND METHODS: Seventeen consecutive patients harboring 21 wide-necked
      saccular cerebral aneurysms were treated with stent reconstruction. Twenty
      aneurysms were unruptured; one was treated within 24 hours of diagnosis of
      rupture. Twenty aneurysms were located in the anterior circulation; one was in
      the posterior circulation. Immediate and six-month post-treatment angiography and
      clinical assessment were performed. RESULTS: In all cases, the stents were
      delivered and positioned without difficulty in deployment. Technical
      complications occurred in 4 patients, but none were directly related to the stent
      delivery system. On immediate post-treatment angiography, 5 of 21 aneurysms
      showed complete occlusion, 5 of 21 showed residual neck, and 11 of 21 showed
      residual contrast filling of the aneurysm sac. At six month follow-up, all 17
      patients were clinically stable. Angiography of 18 of the aneurysms showed total
      occlusion in 12, residual neck in 3, and residual aneurysm filling in 3.
      Retreatment was performed in the three with residual aneurysm. CONCLUSION: The
      Neuroform EZ stent system offers improved anchoring and support in stent
      delivery, which is particularly useful when multiple stents are overlapped to
      further protect the parent vessel and increase flow diversion away from the
      aneurysm sac. The only significant problem encountered was coil prolapse, which
      could be treated with a second stent when necessary. The ease of deployment
      improves upon the already clinically successful Neuroform design.

PMID- 22454784
TI  - Coincidental Occurrence of Acute In-stent Thrombosis and Iatrogenic Vessel
      Perforation During a Wingspan Stent Placement: Management with a Stent In-stent
      Technique.
AB  - We presented a case that an acute in-stent thrombosis after the deployment of a
      Wingspan stent was successfully managed with a stent in-stent technique. Because
      vessel perforation and subarachnoid hemorrhage were iatrogenically developed
      during the procedure, we were unable to use the thrombolytic agents to correct
      the in-stent thrombosis. When a thrombotic complication following an intracranial
      stent placement occurs with a coincidentally hemorrhagic complication, the stent
      in-stent technique should be considered as a treatment option.

PMID- 22454785
TI  - Rapidly Progressive Rhino-orbito-cerebral Mucormycosis Complicated with
      Unilateral Internal Carotid Artery Occlusion: A Case Report.
AB  - Rhinocerebral mucormycosis is an acute fulminant opportunistic fungal infection
      usually seen in diabetic or immunocompromised patients. The fungi that cause
      mucormycosis inoculate the nasal mucosa and may spread to the paranasal sinuses,
      orbit, and brain. Our patient initially presented with mild ethmoid sinusitis. At
      that time, brain MRI and contrast-enhanced MR angiography were grossly normal.
      However, aggravation of sinusitis with extension to the right orbit and anterior
      cranial fossa rapidly developed within two months. Moreover, an occlusion of the
      right internal carotid artery was combined. We report a case of a pathologically
      proven rhino-orbital-cerebral mucormycosis with serial follow-up imaging for over
      one year.

PMID- 22454786
TI  - Foreign body removal by snare loop: during intracranial stent procedure.
AB  - We present a case of successful retrieval of an intracranial stent using a snare
      wire. A 52-year-old woman presented with left border zone infarction. On cerebral
      angiography, the C6 segment of the left internal carotid artery (ICA) showed
      significant stenosis. We attempted stenting of the lesion, although stent
      dislodgement occurred in the ICA C4 segment. We successfully removed it using a
      snare loop, and there were no complications during the procedure.

PMID- 22454787
TI  - Availability of Asthma Quick Relief Medication in Five Alabama School Systems.
AB  - OBJECTIVES: This paper documents individual asthma action plan presence and quick
      relief medication (albuterol) availability for elementary students enrolled in
      five Alabama school systems.  PATIENTS AND METHODS: Data were obtained during
      baseline data collection (fall 2005) of a school-based supervised asthma
      medication trial. All students attended 1 of 36 participating elementary schools
      across five school systems in Jefferson County, Alabama. In addition, they had to
      have physician-diagnosed asthma requiring daily controller medication. Each
      school system had its own superintendent and elected school board. Asthma action
      plan presence and albuterol availability was confirmed by study personnel. Asthma
      action plans had to contain daily and acute asthma management instructions.
      Predictors of asthma action plan presence and albuterol availability were also
      investigated. Associations between albuterol availability and self-reported
      characteristics including health care utilization prior to study enrollment and
      outcomes during the study baseline period were also investigated.  RESULTS:
      Enrolled students had a mean (SD) age of 11.0 (2.1) years, 91% were African
      American, and 79% had moderate persistent asthma. No student had a complete
      asthma action plan on file and only 14% had albuterol physically available at
      school. Albuterol availability was not predicted by gender, race, insurance
      status, second-hand smoke exposure, need for pre-exercise albuterol, asthma
      severity, or self-reported health care utilization prior to study enrollment.
      Albuterol availability did not predict school absences, red/yellow peak flow
      recordings, or medication adherence during the study's baseline period. 
      CONCLUSION: Despite policies permitting students to possess albuterol, few
      elementary students across five independent school systems in Alabama actually
      had it readily available at school.

PMID- 22454788
TI  - How Do Perceptions of Asthma Control and Severity Relate to Indicators of Asthma
      Status and Treatment Recommendations by Pediatricians?
AB  - BACKGROUND: According to National Institutes of Health (NIH) guidelines, asthma
      control and severity are unique constructs. Little is known about how asthma
      control and severity are distinguished by pediatricians and if they influence
      treatment recommendations.  METHODS: We conducted a random-sample survey of 500
      pediatricians using patient vignettes with different asthma status indicators
      (recent hospitalization, parental report of bother from asthma, frequent
      symptoms, parental report of worsening asthma, and wheeze during physical exam)
      and a visual analog scale (VAS) to rate control and severity. Regression models
      assessed the independent effects of these indicators on asthma control and
      severity ratings, and the effects of these ratings on treatment recommendations. 
      RESULTS: A total of 270 respondents provided usable data. Compared to patients
      with well-controlled asthma: (1) medication intensity influenced only severity
      ratings; (2) frequent symptoms and recent hospitalization influenced control and
      severity ratings; (3) wheeze and bother influenced control ratings only (p<0.001
      for all comparisons); (4) a report of worse asthma did not significantly affect
      any ratings (p>0.2). Poorer VAS control ratings were associated with
      recommendations to step-up treatment (odds ratio [OR] 2.61, 95% confidence
      interval [CI], 2.2-3.1, p<0.001), but more severe VAS ratings were not (OR 1.02,
      95% CI, 0.9-1.2, p=0.8). Recommendations to step-down treatment were associated
      with poorer VAS control ratings (OR 0.70, 95% CI, 0.6-0.8, p<0.001) and more
      severe VAS ratings (OR 0.82, 95% CI, 0.7-0.9, p<0.001).  CONCLUSIONS:
      Pediatricians who step-up asthma treatment base their assessments on asthma
      control, while assessments of both control and severity factor into their
      decision to step-down asthma therapy.

PMID- 22454792
TI  - Recognition of psychiatric symptoms and conditions in latino patients.

PMID- 22454793
TI  - Psychological masquerade.

PMID- 22454789
TI  - Neurophysiology of Nicotine Addiction.
AB  - Tobacco use is a major health problem, and nicotine is the main addictive
      component. Nicotine binds to nicotinic acetylcholine receptors (nAChR) to produce
      its initial effects. The nAChRs subtypes are composed of five subunits that can
      form in numerous combinations with varied functional and pharmacological
      characteristics. Diverse psychopharmacological effects contribute to the overall
      process of nicotine addiction, but two general neural systems are emerging as
      critical for the initiation and maintenance of tobacco use. Mesocorticolimbic
      circuitry that includes the dopaminergic pathway originating in the ventral
      tegmental area and projecting to the nucleus accumbens is recognized as vital for
      reinforcing behaviors during the initiation of nicotine addiction. In this neural
      system beta2, alpha4, and alpha6 are the most important nAChR subunits underlying
      the rewarding aspects of nicotine and nicotine self-administration. On the other
      hand, the epithalamic habenular complex and the interpeduncular nucleus, which
      are connected via the fasciculus retroflexus, are critical contributors
      regulating nicotine dosing and withdrawal symptoms. In this case, the alpha5 and
      beta4 nAChR subunits have critical roles in combination with other subunits. In
      both of these neural systems, particular nAChR subtypes have roles that
      contribute to the overall nicotine addiction process.

PMID- 22454794
TI  - Schizoaffective disorder with missed diagnosis of acute porphyria: a case report
      and overview.
AB  - Acute porphyrias are often misdiagnosed and most commonly present as atypical
      neuropsychiatric symptoms or acute abdominal pain. Clinicians should suspect
      acute porphyrias in patients presenting with variable neuropsychiatric symptoms
      and unexplained pain. Proper identification can lead to less iatrogenicity
      associated with porphyrinogenic agents, appropriate management, and a better
      patient outcome. The case of a patient with hereditary coproporphyria, one of the
      acute porphyrias, is presented to illustrate the broad manifestations,
      unsuspected diagnosis, and difficulties in management.

PMID- 22454795
TI  - Crying wolf.

PMID- 22454796
TI  - A case of major depressive disorder and symptoms of polycystic ovary syndrome
      responding to escitalopram.

PMID- 22454797
TI  - A case of dramatic improvement of severe tardive dyskinesia after switch to
      aripiprazole.

PMID- 22454798
TI  - Persistent Psychosis After a Single Ingestion of "Ecstasy" (MDMA).

PMID- 22454799
TI  - A case of galactorrhea with escitalopram: a biopsychosocial phenomenon.

PMID- 22454800
TI  - A case of cerebral venous thrombosis in a 77-year-old white man.

PMID- 22454801
TI  - A 52-week, double-blind evaluation of the metabolic effects of aripiprazole and
      lithium in bipolar I disorder.
AB  - INTRODUCTION: Metabolic risk factors, termed metabolic syndrome, which include
      obesity, diabetes, dyslipidemia, and hypertension, are more common in patients
      with bipolar disorder than in the general population. Moreover, medications used
      to treat bipolar disorder carry some risk of worsening metabolic parameters.
      METHOD: The study was conducted at 46 study centers in the United States,
      although only 31 study centers enrolled patients in the 40-week extension phase.
      Patients with acute bipolar I mania, manic or mixed (DSM-IV-TR criteria; Young
      Mania Rating Scale score >= 20), who required hospitalization were randomly
      assigned to double-blind aripiprazole (15-30 mg/d), lithium (900-1500 mg/d), or
      placebo for 3 weeks. Patients treated with aripiprazole or lithium continued
      treatment to week 12, after which they could enter a double-blind 40-week
      extension phase. Patients were enrolled in the 12-week acute treatment phase
      between April 2004 and July 2006; the first patient entered extension treatment
      in October 2004, and the last patient completed treatment in May 2007. Changes in
      metabolic parameters were compared between patients treated with aripiprazole or
      lithium for up to 52 weeks using last observation carried forward and analysis of
      covariance. Analysis stratified by baseline body mass index (BMI) was also
      conducted. RESULTS: Modest increases in body weight were observed in both groups:
      +0.97 kg (2.1 lb) for aripiprazole (n = 127) and + 0.74 (1.6 lb) for lithium (n =
      136), P = .60. A significant difference in body weight increase was observed only
      among patients with a BMI < 25: + 2.66 kg (5.9 lb) for aripiprazole (n = 35) and
      + 0.40 kg (0.9 lb) for lithium (n = 37), P = .02. Mean changes from baseline to
      week 52 in fasting levels of total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, plasma glucose, triglycerides,
      or insulin (last observation carried forward) were small in both aripiprazole and
      lithium treatment groups; no significant differences were observed. Mean
      laboratory values were within the normal or borderline range for both treatment
      groups across all BMI categories. CONCLUSION: Comparably modest and similar
      changes in metabolic parameters were observed in patients with bipolar disorder
      treated for up to 1 year with either lithium or aripiprazole. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00095511.

PMID- 22454802
TI  - Bright light treatment as add-on therapy for depression in 28 adolescents: a
      randomized trial.
AB  - BACKGROUND: In the last decade, a significant incidence of depression in the
      younger population has been observed. Bright light therapy, an effective
      therapeutic option for depressed adults, could also provide safe, economical, and
      effective rapid recovery in adolescents. METHOD: The randomized trial included 28
      inpatients (18 females and 10 males) between 14 and 17 years old with depressive
      complaints. The study was conducted between February and December of 2010 in
      Rodewisch, Germany. Half of the patients (n = 14) first received placebo (50 lux)
      1 hour a day in the morning from 9:00 am to 10:00 am for 1 week and then received
      bright light therapy (2,500 lux) for 1 week in the morning from 9:00 am to 10:00
      am. The other half (n = 14) first received bright light therapy and then received
      placebo. Patients were encouraged to continue ongoing treatment (fluoxetine 20
      mg/day and 2 sessions of psychotherapy/week) because there were no changes in
      medication/dosage and psychotherapy since 1 month before the 4-week study period.
      For assessment of depressive symptoms, the Beck Depression Inventory (BDI) was
      administered 1 week before and 1 day before placebo treatment, on the day between
      placebo and bright light treatment, and on the day after and 1 week after bright
      light treatment. Saliva samples of melatonin and cortisol were collected at 8:00
      am and 8:00 pm 1 week before and 1 day before placebo treatment, on the day
      between placebo and bright light treatment, on the day after bright light
      treatment, and 1 week after bright light treatment and were assayed for melatonin
      and cortisol to observe any change in circadian timing. RESULTS: The BDI scores
      improved significantly (P = .015). The assays of saliva showed significant
      differences between treatment and placebo for evening melatonin (P = .040). No
      significant adverse reactions were observed. CONCLUSIONS: Antidepressant response
      to bright light treatment in this age group was statistically superior to
      placebo. TRIAL REGISTRATION: World Health Organization International Clinical
      Trials Registry Platform identifier: DRKS00003309.

PMID- 22454803
TI  - Self-reported alcohol and drug problems among internal medicine outpatients:
      relationships with criminal behavior.
AB  - OBJECTIVE: Previous research indicates relationships between alcohol/substance
      misuse and criminal behavior, but past studies have restricted investigations to
      atypical samples and/or utilized limited assessments of illegal behavior. In the
      present study, we explored relationships between alcohol/drug problems and
      charges for 27 criminal behaviors in a primary care sample. METHOD: Participants
      were a cross-sectional sample of 376 consecutive men and women, aged 18 years or
      older, being seen for nonemergent medical care at an outpatient internal medicine
      clinic staffed predominantly by residents and located in a midsized, midwestern
      city in October 2010. Using a self-report survey methodology, we examined
      relationships between alcohol and drug problems ("Have you ever had a problem
      with alcohol?" and "Have you ever had a problem with drugs?") and 27 illegal
      behaviors as delineated by the categories used by the US Federal Bureau of
      Investigation. RESULTS: Men with alcohol or drug problems statistically exhibited
      the greatest number of charges for different forms of illegal behavior (P <
      .001). These charges were directly related to alcohol/drug misuse (eg, driving
      under the influence of alcohol or drugs) and otherwise (eg, aggravated assault,
      simple assault, gambling, larceny-theft). CONCLUSIONS: In primary care settings,
      men with alcohol/drug problems may also have a history of illegal behaviors-a
      finding that is relevant in terms of social and legal implications.

PMID- 22454804
TI  - Transdermal patches for the treatment of neurologic conditions in elderly
      patients: a review.
AB  - OBJECTIVE: The mode of drug delivery can be an important consideration in
      optimizing drug therapy, as it can affect treatment compliance and outcomes. It
      is particularly important to develop optimal drug formulations for chronic
      diseases or conditions in the elderly for which treatment compliance is known to
      be low. In this review, the features and benefits of transdermal formulations for
      treating neurologic conditions in elderly patients are described. DATA SOURCES:
      English-language articles were identified by searching MEDLINE in November 2010
      (there were no search parameters on date of publication) using the search terms
      transdermal patch, transdermal system, neurology, rivastigmine, rotigotine,
      selegiline, lidocaine, capsaicin, compliance, and neuropathic pain. DATA
      SELECTION: Articles describing the development, use, efficacy, and safety of
      licensed transdermal patch treatments for neurologic conditions that affect the
      elderly were included. DATA EXTRACTION: The features of transdermal systems and
      comparisons between transdermal and oral formulations for the treatment of
      specific neurologic conditions in elderly patients were reviewed. DATA SYNTHESIS:
      There are 5 transdermal patch systems currently available for neurologic
      conditions in adults: rivastigmine, rotigotine, selegiline, lidocaine, and
      capsaicin. These are all modern formulations in matrix patches, developed to
      provide appropriate drug dosage in an acceptable and well-tolerated form.
      CONCLUSIONS: Transdermal patches can offer benefits to patients over oral
      formulations in terms of ease of use, simple treatment regimens, avoidance of the
      first-pass effect, and avoidance of high maximum plasma concentrations with rapid
      changes in drug levels, without the invasive procedures associated with
      intravenous treatment.

PMID- 22454805
TI  - Treating attention-deficit/hyperactivity disorder in adults: focus on once-daily
      medications.
AB  - OBJECTIVE: To review the efficacy, safety, and abuse liability of approved
      treatments in adults with attention-deficit/hyperactivity disorder (ADHD), with a
      focus on once-daily medications. DATA SOURCES: PubMed was searched for relevant
      studies/reviews in English from 2002 to 2011 on adult ADHD treatments. STUDY
      SELECTION: Keywords used in the search were ADHD, adults, and treatment. Limits
      included only clinical trials, meta-analyses, randomized controlled trials, and
      reviews including adults (aged >= 19 years). DATA EXTRACTION: Selection criteria
      returned 471 publications. Retrieved studies were excluded if they primarily
      focused on children, treatments not indicated for ADHD, or ADHD and comorbid
      conditions. DATA SYNTHESIS: An epidemiologic survey revealed that 10.9% of adults
      identified with ADHD had received treatment during the prior 12 months.
      Treatments for ADHD in adults include pharmacologic and nonpharmacologic options.
      US Food and Drug Administration-approved long-acting stimulants and a
      nonstimulant with proven efficacy and safety profiles have been developed and
      include osmotic-release oral system methylphenidate hydrochloride (OROS
      methylphenidate), extended-release dexmethylphenidate hydrochloride, mixed
      amphetamine salts extended release (MAS-XR), the nonstimulant atomoxetine
      hydrochloride, and the prodrug lisdexamfetamine dimesylate. Long-acting
      stimulants differ in formulation characteristics used to achieve extended
      release, with OROS-methylphenidate employing an osmotic-release technology,
      extended-release dexmethylphenidate hydrochloride and MAS-XR using pH-dependent
      beads, and lisdexamfetamine dimesylate using prodrug technology. These features
      variably affect pharmacokinetic characteristics, duration of action, and abuse
      liability. While all long-acting medications have varied pharmacokinetic
      features, mechanism of action, and duration of effect, all are generally
      efficacious and safety profiles are similar. CONCLUSION: Approved long-acting
      treatments in adults with ADHD were effective in improving symptoms and were
      generally well tolerated.

PMID- 22454806
TI  - Olanzapine-induced weight gain in patients with bipolar I disorder: a meta
      analysis.
AB  - OBJECTIVE: The weight impact produced by the atypical antipsychotic olanzapine
      has been explored in meta-analyses focusing on patients with schizophrenia.
      However, outcomes identified for schizophrenia patients cannot always be
      generalized to patients with bipolar disorder. This study aims to quantitatively
      estimate the impact of olanzapine on the weight of patients with bipolar
      disorder. DATA SOURCES: EMBASE, Medline, and PsycINFO were searched using the
      keywords olanzapine AND (bipolar OR acute mania) in conjunction with (weight gain
      OR weight increase) (last search: October 2010, with no restrictions on dates of
      publication). English language was used as a restriction. STUDY SELECTION: The
      search identified 110 articles for review. The inclusion criteria for the chosen
      studies were a diagnosis of bipolar disorder, the presence of an olanzapine
      monotherapy group, a comparator placebo or monotherapy group, and mean weight
      gain and/or incidences of weight gain data. This process identified 13 studies
      for inclusion. DATA EXTRACTION: The primary outcome measure was the mean weight
      change between olanzapine monotherapy and comparator monotherapy, reported in
      kilograms. Standard deviation was extracted directly from studies when possible
      and imputed for 3 studies. The secondary outcome measure was the reported
      incidences of >= 7% weight gain. DATA SYNTHESIS: The mean difference in weight
      gain was calculated for the continuous data of the primary outcome. Olanzapine
      monotherapy was associated with more weight gain when compared to placebo (mean
      difference = 2.10 kg; 95% CI, 1.16-3.05; P < .001) and other bipolar monotherapy
      (mean difference = 1.34 kg; 95% CI, 0.95-1.72; P < .001). Odds ratio analysis of
      the dichotomous secondary outcome also showed more weight gain with olanzapine
      monotherapy compared to placebo (odds ratio [OR] = 10.12; 95% CI, 1.93-53.14; P =
      .006) and other bipolar monotherapy (OR = 2.09; 95% CI, 1.27-3.44; P = .004).
      CONCLUSIONS: Currently available data suggest that olanzapine is associated with
      significant weight gain in bipolar patients. Issues related to side effect
      profiles and their impact on treatment compliance and physical health outcomes
      need to be considered when selecting pharmacotherapy.

PMID- 22454807
TI  - Efficacy of duloxetine on painful physical symptoms in major depressive disorder
      for patients with clinically significant painful physical symptoms at baseline: a
      meta-analysis of 11 double-blind, placebo-controlled clinical trials.
AB  - OBJECTIVE: To review efficacy of duloxetine for physical symptoms and depressive
      illness in patients with at least mild to moderate major depressive disorder
      (MDD; DSM-IV) and clinically significant painful physical symptoms at baseline.
      DATA SOURCES: Global database of duloxetine clinical trials (Eli Lilly and
      Company). STUDY SELECTION: All 11 acute, double-blind, placebo-controlled studies
      of duloxetine (7 with duloxetine 60-mg doses and 4 with non-60-mg doses) in the
      database that used a scale to measure painful physical symptoms and were
      completed before March 17, 2011. DATA EXTRACTION: For each study, patients with
      clinically significant pain levels at baseline (Visual Analog Scale overall pain
      rating >= 30, Numerical Rating Scale score >= 3, or Brief Pain Inventory 24-hour
      average pain rating >= 3) were selected in order to determine the effect sizes of
      duloxetine (compared with placebo for each trial) on the pain and depression
      measures. Overall effect sizes for both painful physical symptoms and MDD were
      obtained from the mean of individual-trial effect sizes, and each effect size was
      weighted relative to the number of patients within each study. DATA SYNTHESIS:
      The overall mean effect sizes were as follows: painful physical symptoms-60-mg
      trials, 0.29 (95% CI, 0.06 to 0.52); non-60-mg trials, 0.13 (95% CI, -0.19 to
      0.45); MDD-60-mg trials, 0.29 (95% CI, 0.18 to 0.40); non-60-mg trials, 0.16 (95%
      CI, 0.00 to 0.32). Across the 11 studies, the weighted effect size for painful
      physical symptoms was 0.26 (95% CI, 0.00 to 0.51) and for MDD, 0.25 (95% CI, 0.16
      to 0.34). CONCLUSIONS: According to this meta-analysis, duloxetine 60 mg once
      daily is as effective in improving painful physical symptoms as it is for
      depression in patients with MDD and clinically significant painful physical
      symptoms. The results of this meta-analysis indicate that duloxetine has small
      effect sizes in reducing painful physical symptoms and depressive symptoms in
      patients with MDD and clinically significant pain levels at baseline. Thus, the
      results of the study permit one to conclude that duloxetine has a clinically
      significant impact on painful physical symptoms and in reducing the severity of
      depressive symptoms. However, the results do not address its efficacy compared to
      other alternatives, as in all studies the comparator was placebo.

PMID- 22367489
TI  - Effect of the rd1 mutation on motor performance in R6/2 and wild type mice.
AB  - Homozygosis for the rd1 mutation in the Pbe6b gene results in the loss of the rod
      beta-subunit of the cyclic GMP phosphodiesterase and, eventually, of all rod and
      cone photoreceptors. The R6/2 mouse line is a widely used model of Huntington's
      disease (HD). The original line was made available on a mixed background obtained
      by crossing, via ovarian transplant, female R6/2 (on a B6CBA mixed background)
      with male B6CBAF1/J mice. As the CBA/J strain used in the US is homozygous for
      the rd1 mutation and the breeding scheme does not ensure heterozygosis for the
      mutation, a significant percentage of the offspring on this mixed background is
      expected to be homozygous for the rd1 mutation. We investigate here the effect of
      rd1 homozygosis on motor function and examined the effects of the mutation on the
      R6/2 phenotype. Homozygosis for the rd1 mutation resulted in increased activity
      in the open field test and reduced rotarod test performance. In addition, rd1
      mutation absence or heterozygosis reduced the differences between the R6/2 and
      the WT mice. Our recommendation for the neurodegeneration field, and for all
      mouse studies in general, is to carefully control homozygosis for retinal
      degeneration mutation, even when using tests of motor function.

PMID- 22454809
TI  - Methamphetamine-induced paralytic ileus.
AB  - Methamphetamine abuse has become a significant problem in the United States with
      recent surveys reporting that nearly 10 million Americans have tried
      methamphetamine at least once. Methamphetamine is a stimulant drug that causes
      the release of monoamine neurotransmitters. Among its most deleterious effects
      are its ability to produce tachycardia, hypertension, and ischemia. However, it
      also has the potential to cause clinically significant effects outside of the
      cardiovascular system although a case of paralytic ileus caused by
      methamphetamine use has not been described before in the literature. Described is
      a case in which a patient presented with chest and abdominal pain after
      methamphetamine use. The patient was ultimately diagnosed with a methamphetamine
      induced paralytic ileus.

PMID- 22454810
TI  - Science in liquid dietary supplement promotion: the misleading case of mangosteen
      juice.
AB  - Liquid dietary supplements represent a fast growing market segment, including
      botanically-based beverages containing mangosteen, acai, and noni. These products
      often resemble fruit juice in packaging and appearance, but may contain
      pharmacologically active ingredients. While little is known about the human
      health effects or safety of consuming such products, manufacturers make extensive
      use of low-quality published research to promote their products. This report
      analyzes the science-based marketing claims of two of the most widely consumed
      mangosteen liquid dietary supplements, and compares them to the findings of the
      research being cited. The reviewer found that analyzed marketing claims overstate
      the significance of findings, and fail to disclose severe methodological
      weaknesses of the research they cite. If this trend extends to other related
      products that are similarly widely consumed, it may pose a public health threat
      by misleading consumers into assuming that product safety and effectiveness are
      backed by rigorous scientific data.

PMID- 22454811
TI  - A case of Salmonella gastroenteritis following ingestion of raw venison sashimi.
AB  - An interesting case of gastroenteritis due to Salmonella Birkenhead following
      ingestion of raw venison sashimi is described. A 65-year-old man presented with
      diarrhea, vomiting, and fever. On exam he was hypotensive, tachycardic, with
      evidence of severe dehydration following ingestion of raw venison sashimi
      produced with game meat hunted on the Hawaiian island of Lana'i. He responded
      rapidly to vigorous volume resuscitation, and stool cultures later were positive
      for Salmonella Birkenhead. Non-typhoidal Salmonella is the most frequently
      identified cause of foodborne illness in the United States. Clinicians in the
      state of Hawai'i should be alert and aware of the potential for the local deer
      population to be an unusual source of foodborne illness, especially given the
      prevalence of consumption of raw foods in the local cuisine.

PMID- 22454812
TI  - Public health hotline: using policy to influence health behaviors.

PMID- 22454813
TI  - Medical school hotline: importance of research in medical education.

PMID- 22454814
TI  - UH Cancer Center hotline: modern medicine and the road to prevention: a long and
      tortuous path.

PMID- 22454817
TI  - Subcutaneous emphysema, pneumopericardium, pneumomediastinum and
      pneumoretroperitoneum secondary to sigmoid perforation: a case report.
AB  - A 50-year-old woman presented with chronic epigastric abdominal pain and
      constipation. She underwent diagnostic upper and lower endoscopy for further
      evaluation. Several hours following the procedure, she developed chest and
      subcutaneous emphysema of her upper chest, neck, and face. A chest X-ray
      demonstrated marked subcutaneous emphysema, pneumopericardium, and
      pneumomediastinum. A CT scan revealed a small leak at the rectosigmoid junction.
      Because the patient did not have peritoneal signs, she was treated conservatively
      and discharged on hospital day seven. The complications of both
      esohagogastroduodenoscoy, and colonoscopy are discussed, with an emphasis on
      perforations.

PMID- 22454816
TI  - Sexually transmitted disease (STD) update: a review of the CDC 2010 STD treatment
      guidelines and epidemiologic trends of common STDs in Hawai'i.
AB  - The US Centers for Disease Control and Prevention recently updated its
      recommendations for treating sexually transmitted diseases (STDs). In this review
      we highlight new treatment recommendations for mitigating the increasing
      prevalence of antibiotic-resistant Neisseria gonorrhoeae, the emergence of
      azithromycin-resistant Treponema pallidum, and treatment options for bacterial
      vaginosis and venereal warts. We also cover epidemiologic trends for common STDs
      in Hawai'i.

PMID- 22454818
TI  - Public health hotline: advancing public health today and for future generations.

PMID- 22454819
TI  - Medical school hotline: transition to clerkship week at the John A. Burns School
      of Medicine.

PMID- 22454821
TI  - The Influence of Pathologies upon Sensory Perception and Sensory Coordination in
      Children with Developmental Dyslexia and Learning Disorders: A Unified Theory of
      Developmental Dyslexia.
AB  - This case is presented to explain that developmental dyslexia and related
      autistic spectrum disorders have solely pathological origins. There is a general
      consensus of opinion which supports the phonological theory. However, this
      largely ignores the biological basis for all aspects of the brain's development
      and function, and hence, for its dysfunction. A unified explanation must take
      into account all salient features including cognitive dysfunction, encephalograph
      (EEG) frequencies, neural networks, physiological systems, autonomic nervous
      system and the function of the cerebellum. It must explain the significance of
      the brain waves and neurons and their normally synchronized or coherent function.
      This article builds upon an earlier article by the authors, which incorporates a
      review and discussion of the prevailing theories or models for developmental
      dyslexia. It looks at the issues from a top-down 'systems biology' perspective.
      It concludes that it may be only the body's biochemistry and, in particular, the
      onset of pathologies that explain the phenomena which we recognize as
      developmental dyslexia. Pathologies experienced in the early prepubescent years
      influence neural development. They influence the speed and coherent transmission
      of data between the senses and neural centers. It is proposed that this explains
      the nature and occurrence of what we recognize as developmental dyslexia.

PMID- 22454822
TI  - Trigger digits and diabetes mellitus.
AB  - The problem of finger in the patient with diabetes mellitus is important
      consideration in diabetology. Generally, peripheral neuropathy that manifests
      with finger paresthesia is common. However, some recent reports mention the
      concern on trigger digits in diabetic patients. In this brief article, the
      authors focus review and discussion on this specific topic. The searching of
      standard database, PubMed, on available publication on this area selecting by
      keywords trigger digits and diabetes mellitus was done and all derived papers
      were extracted and further synthesized in this review article. Epidemiology and
      management of the condition are the mainly focused reviewed areas and presented
      in this article.

PMID- 22454823
TI  - Distribution of CD4 Lymphocyte Cells Among Apparently Healthy HIV Seropositive
      and Seronegative Populations.
AB  - BACKGROUND: CD4 lymphocyte cells are often used as prognostic markers for
      monitoring the progression of immunosupression such as HIV infection. AIM: This
      study was conducted to assess the distribution of CD4 lymphocytes among
      apparently healthy human immunodeficiency virus (HIV) seronegative and
      seropositive populations in a Nigerian state. MATERIALS AND METHODS: A total of
      1520 apparently healthy subjects aged 18-64 years, composed of 800 males and 720
      females attending some selected health institutions in the state, participated in
      the study. Ten milliliters of blood was collected from each subject; 5 ml of this
      was used for HIV antibodies sero-typing while the remaining 5 ml was
      anticoagulated and used for CD4 lymphocytes level determination. Only samples
      tested positive both with Capillus and Determine HIV test kits were further
      differentiated into sero-types with a standard diagnostic HIV test kit. The CD4
      lymphocyte levels of all the sample were determined; mean CD4 levels of 205.1+/
      0.09 and 287.4+/-0.3 cells/MUl were recorded among females seropositives and
      seronagatives respectively. Statistical analysis by the Student t-test showed a
      significant difference in the mean CD4 lymphocyte count by gender. RESULTS:
      Findings showed a mean CD4 level of 311.7+/-1.2 cells/MUl among seropositive
      males while 399.3+/-0.6 cells/MUl was recorded among seronegatives (t=5.86). The
      study also recorded a CD4 lymphocyte range of 232-464 cells/MUl among apparently
      healthy seronegative population in this locality. CONCLUSION: The findings showed
      a significantly higher mean CD4 lymphocyte count among adult male HIV
      seronegatives (chi(2)=9.22) and seropositives (chi(2)=15.07) than their female
      counterparts. Further research work using the automation technique is suggested
      to confirm this new range for monitoring HIV subjects on antiretroviral therapy.

PMID- 22454824
TI  - CD4 lymphocyte count: A Barometer for HIV/AIDS Management.

PMID- 22454825
TI  - Malondialdehyde levels in oral sub mucous fibrosis: a clinicopathological and
      biochemical study.
AB  - BACKGROUND: Oral submucous fibrosis is one of the most commonly occurring
      potentially malignant disorders in the South-East Asia. Levels of lipid
      peroxidation product malondialdehyde have been recently correlated with clinical
      grades of oral Submucous fibrosis. AIMS: The aims of this study were to estimate
      the levels of malondialdehyde in serum, saliva and tissue in patients with oral
      submucous fibrosis, to correlate change in levels of malodialdehyde with the
      histopathological grading. MATERIALS AND METHODS: The study group comprised of 65
      clinically diagnosed and histopathologically confirmed cases of oral submucous
      fibrosis, 21 age and sex matched controls were also enrolled into the study. The
      serum saliva and tissue samples in the study groups were evaluated by the
      thiobarbutric acid reactive substances. RESULTS: There was a significant
      difference between the serum and salivary malondialdehyde among the
      histopathological grades of oral submucous fibrosis. Tissue malonaldehyde levels
      were significantly higher as the grading progressed but tissue levels in grade 3
      oral submucous fibrosis were lower than the controls. CONCLUSION: This decrease
      in tissue malonaldehyde could possibly be associated to collagen cross linking
      occurring during the advanced stages of oral submucous fibrosis.

PMID- 22454826
TI  - Incidence, patterns, and factors predicting mortality of abdominal injuries in
      trauma patients.
AB  - BACKGROUND: Abdominal trauma is a major public health problem for all nations and
      all socioeconomic strata. AIM: This study was designed to determine the incidence
      and patterns of abdominal injuries in trauma patients. MATERIALS AND METHODS: We
      classified and identified the incidence and subtype of abdominal injuries and
      associated trauma, and identified variables related to morbidity and mortality.
      RESULTS: Abdominal trauma was present in 248 of 300 cases; 172 patients with
      blunt abdominal trauma and 76 with penetrating. The most frequent type of
      abdominal trauma was blunt trauma; its most common cause was motor vehicle
      accident. Among patients with penetrating abdominal trauma, the most common cause
      was stabbing. Most abdominal trauma patients presented with other injuries,
      especially patients with blunt abdominal trauma. Mortality was higher among
      penetrating abdominal trauma patients. CONCLUSIONS: Type of abdominal trauma,
      associated injuries, and Revised Trauma Score are independent risk factors for
      mortality in abdominal trauma patients.

PMID- 22454827
TI  - Toxicological Assessment of the Cochleate Derived from Neisseria meningitidis
      Proteoliposome in Sprague Dawley Rats.
AB  - BACKGROUND: The AFCo1 cochleate is a potential novel adjuvant derived from
      Neisseria meningitidis B proteoliposome. AIM: The aim was to assessing the safety
      of AFCo1 by single and repeated doses in Sprague Dawley rats. MATERIALS AND
      METHODS: Rats were grouped for treatment with AFCo1, placebo formulation or
      control. The first study was a single intranasal dose of 100 MUl and monitoring
      body weight, water, and food intakes as well as clinical symptoms. Fourteen days
      later the rats were killed and anatomopathological studies were conducted. In a
      second study, four similar doses of the test substance were instilled every 5
      days. Clinical observations were carried out as for the single dose study and a
      number of rats from each group were killed 3 and 14 days after the last dose in
      order to conduct hematological, hemochemical, and anatomopathological studies.
      RESULTS: No variable showed differences of toxicological relevance; the
      histological changes found were mild and similarly frequently in the three
      groups. According to the irritability index calculated form histology of the
      nasal region, AFCo1 was also classified as nonirritating. CONCLUSION: AFCo1 is
      potentially safe for human use by nasal route as evidenced by the absence of
      local and systemic signs of toxicity in Sprague Dawley rats.

PMID- 22454828
TI  - Thalassemia Major in Adults: Short Stature, Hyperpigmentation, Inadequate
      Chelation, and Transfusion-Transmitted Infections are Key Features.
AB  - BACKGROUND: Effective transfusion and chelation have prolonged the quality and
      longevity of life in thalassemics, who now survive into adulthood. Hence, adult
      physicians need to be aware of their clinical and laboratory profile and the
      problems faced by them. AIM: The present study was aimed to evaluate the clinical
      profile of adult thalassemics. MATERIALS AND METHODS: Adult (>18 years)
      thalassemia major patients (n=19) were evaluated clinically and fasting
      pretransfusion blood samples were analyzed for complete blood counts, kidney and
      liver function tests, plasma glucose, serum ferritin, and thyroid hormone levels.
      RESULTS: Average age was 21.65+/-2.47 years (range 19-28 years), 42.1% had Body
      mass index (BMI) <18.5. Splenectomy had been performed in 47.4% before reaching
      adulthood, males significantly outnumbered females (72% vs. 12.5%). Hemoglobin
      levels <8 g/dl were observed in 31.6% and none had serum ferritin levels in the
      recommended range suggesting inadequacy of both transfusion and chelation.
      Indirect hyperbilirubinemia was observed in 21.1% patients although kidney
      functions, serum protein, and albumin were normal in all patients.
      Electrocardiographic abnormalities, diabetes mellitus or hypothyroidism were
      absent. Five patients (26.3%) had contracted transfusion-transmitted viral
      infections - 21.1% and 5.3% respectively had antibodies to hepatitis C virus and
      HIV, while 5.3% were positive for Australia antigen. All patients were receiving
      chelation therapy - deferiprone alone (78.9%) or along with desferrioxamine
      (21.1%). Average dose of deferiprone being used was 95+/-8 mg/kg. CONCLUSION:
      Adult thalassemia major patients present with a distinct clinical profile having
      low BMI, generalized hyperpigmentation, most are splenectomized, have low
      hemoglobin, inadequate chelation and harbor transfusion-transmitted infections.
      Adult physician needs to be aware of this profile.

PMID- 22454829
TI  - Thalassemia major: the present and the future.

PMID- 22454830
TI  - Clinico-epidemiological characteristics of patients presenting with
      organophosphorus poisoning.
AB  - BACKGROUND: Organophosphorus (OP) poisoning is a major health problem all over
      the world, particularly in the developing countries. AIM: The present study aims
      to explore the clinical and epidemiological features found in patients presenting
      with OP poisoning. MATERIALS AND METHODS: A 1-year cross-sectional study was
      conducted on patients presenting with clinical features of OP poisoning in a
      tertiary care medical college. RESULTS: A total of 968 patients presented during
      the study period. Poisoning with suicidal intent (82.02%) was more common than
      the accidental one (17.98%). Majority of the patients were housewives (42%)
      followed by farmers, shopkeepers, laborers, students. Methyl parathion was the
      most common poison consumed by the patients (35.74%) followed by diazinon,
      chlorpyriphos, dimicron. Nausea and vomiting (85.02%) was the most common symptom
      while miosis was the most common sign observed in 91.94% patients. A total of 56
      patients of OP poisoning died (5.78%) with respiratory failure being the primary
      cause of death followed by CNS depression, cardiac arrest, and septicaemia.
      CONCLUSION: The present study showed that majority of the patients were of young
      age with females outnumbering males. Poisoning with suicidal intent was more
      common than accidental. Nausea and vomiting was the most common symptom reported
      by the patients while miosis was the most common sign observed by the treating
      physicians of the research team.

PMID- 22454831
TI  - An Unusual Case of Hashimoto's Thyroiditis with Four Lobed Thyroid Gland.
AB  - Hashimoto's thyroiditis (HT), an autoimmune disorder, is the most prevalent cause
      of subclinical or overt hypothyroidism in areas with sufficient iodine intake.
      The gland is often diffusely enlarged, and the parenchyma is coarsened,
      hypoechoic, and often hypervascular on ultrasonograpy. Histopathologic appearance
      of HT includes lymphocyte aggregates with germinal centers, small thyroid
      follicles, presence of Hurthle cells, and variable fibrosis. We present a case of
      a 40-year-old female with suspected follicular neoplasm on fine-needle aspiration
      cytology of neck swelling. Intraoperatively, thyroid gland was found having four
      lobes separated from each other. Total thyroidectomy was done and histopathology
      from all four lobes revealed HT. At present, there is no literature to support
      the fact that such distorted thyroid anatomy may be due to the underlying
      disease. If we consider it as thyroid gland anomaly, no such anomaly has been
      mentioned in the literature till date.

PMID- 22454832
TI  - Multiple vascular anomalies involving testicular, suprarenal arteries and lumbar
      veins.
AB  - Testicular arteries arise from the abdominal aorta and the inferior suprarenal
      artery from the renal artery. There are reports about variant origin and course
      of these arteries. Accessory testicular artery is also a common finding but its
      providing origin to inferior suprarenal artery is an important observation.
      During a routine dissection of abdomen of approximately 55-year-old male cadaver,
      unique vascular abnormality was observed. On the left side, a common arterial
      trunk originating from abdominal aorta immediately branched to give rise to
      superior testicular and inferior suprarenal arteries, the former after a short
      course hooked by the left suprarenal vein. In addition, the left suprarenal vein,
      second left lumbar vein, and left testicular vein joined to form a common trunk
      which drained into the left renal vein. A sound knowledge of vascular variations
      in relation to the kidney and suprarenal gland is important to surgeons
      dissecting the abdominal cavity.

PMID- 22454834
TI  - Stable-isotope dilution GC-MS method for ethanol in vapour ethanol and
      microdialysis systems based on carbonate-catalyzed extractive
      pentafluorobenzoylation.
AB  - Common ethanol detection methods are not applicable to cell culture media and
      microdialysates due to interference with medium constituents including amino
      acids and pH indicators. We present a novel GC-MS method for the accurate and
      precise analysis of ethanol in cell cultures and microdialysates. The method is
      based on the carbonate-catalyzed extractive pentafluorobenzoylation of ethanol
      and deuterium-labelled ethanol serving as the internal standard and on their GC
      MS analysis in the electron-capture negative-ion chemical ionization mode. The
      method was used to optimize experimental conditions in a custom-made ethanol
      vapour system utilized for studies examining ethanol influences on neuronal cell
      lines and in microdialysis.

PMID- 22454833
TI  - A new analytical method based on anti-EPO monolith column and LC-FAIMS-MS/MS for
      the detection of rHuEPOs in horse plasma and urine samples.
AB  - Recombinant human erythropoietin (rHuEPO) is a 30-34 kDa glycoprotein banned by
      the racing authorities. For some years this molecule has been detected in race
      horses in USA and in Europe, and even in racing camels. Although direct methods
      to differentiate horse endogenous EPO and rHuEPO have been developed either by LC
      MS/MS or by isoelectric focusing (IEF) with double-blotting, the short
      confirmation time of such prohibited hormone in plasma remains a problem for
      horseracing doping control laboratories. In order to improve the rHuEPOs
      confirmation process in horse plasma or urine in terms of reliability and delay,
      a small anti-EPO monolith membrane contained in a disposable column (anti-EPO
      monolith column) has been successfully used and validated (n = 10). This new
      sample preparation, combined with LC-FAIMS-MS/MS, has been performed on plasma
      and urine samples collected from one horse which received an Eprex(r) treatment
      during six consecutive days and a second one with a single injection of
      Aranesp(r). This inventive technology allowed the possibility to confirm the
      presence of rHuEPO within one day with a limit of detection validated for both
      urine and plasma at 250 pg mL(-1) by means of a disposable, ready to use
      immunoaffinity column. The lower limit of detection (LLOD) obtained for each
      matrix was 100 pg mL(-1). These results provide an important improvement for
      rHuEPO doping control in horseracing especially the possibility to confirm these
      banned molecules in both matrices, urine and plasma, with a confidence of two
      specific target peptides.

PMID- 22454835
TI  - Real-time separation of natural products by ultrafast 2D NMR coupled to on-line
      HPLC.
AB  - Hyphenated HPLC-NMR is an extremely efficient analytical tool, which makes it
      possible to perform on-flow experiments where 1D NMR spectra are obtained in real
      time as the analytes are separated and eluted from the chromatographic column.
      However, it is incompatible with multidimensional NMR methods that form an
      indispensible tool for the study of complex mixtures. Recently, Frydman and co
      workers have proposed an ultrafast 2D NMR approach, where a complete 2D NMR
      correlation can be recorded in a single scan, thus providing a solution to the
      irreversibility of hyphenated techniques. This paper presents the first
      implementation of on-line ultrafast HPLC-NMR. Ultrafast COSY spectra are acquired
      every 12 s in the course of a chromatographic run performed on a mixture of
      natural aromatic compounds. The results, obtained on a commercial HPLC-NMR setup,
      highlight the generality of the ultrafast HPLC-NMR methodology, thus opening the
      way to a number of applications in the numerous fields in which HPLC-NMR forms a
      routine analytical tool.

PMID- 22454836
TI  - A solvation-based screening approach for metabolite arrays.
AB  - This paper explores a new method for screening metabolites in an array format
      based on relative polarity using selective solvent dissolution. A synthetic
      cocktail of metabolites was spotted onto a hydrophobic silicon surface, and
      solubilised with solvents of varying polarity. The metabolites retained on the
      silicon surface after the solvent treatments were detected using time-of-flight
      static secondary ion mass spectrometry (ToF-sSIMS). Solvent-specific metabolite
      retention was clearly evident on multivariate analysis of the dataset, using
      principal component analysis. Selective removal of metabolites was observed when
      solvents with different polarity were used, with the metabolite retention or
      removal in most cases correlating to the polarity of the solvent used, although
      consideration of other forces in operation may be needed to arrive at fully
      predictable behaviours. This approach provides the basis for development of a
      technique to separate complex metabolites into simpler constituents in a
      metabolite array prior to identification and quantification using mass
      spectrometry. It is an analytical approach that is intermediate between the more
      rapid but less informative direct analysis methods (such as DIMS) that do not
      involve any analyte separations and the more comprehensive but time consuming
      methods (such as GC- and LC-MS) that involve chromatographic or electrophoretic
      separations. The approach has the potential to be successfully developed for
      rapid, yet informative screening of metabolomes.

PMID- 22454837
TI  - Fluorometric sensor based on bisterpyridine metallopolymer: detection of cyanide
      and phosphates in water.
AB  - A poly(ethylene glycol) (PEG) decorated bis(terpyridine) zinc coordination
      polymer acts as an anion-responsive material in 100% aqueous solution. Depending
      on the binding and association constants to Zn(II), the addition of different
      anions leads to increased emission intensity and/or a shift of the emission
      wavelength. The sensor was addressed with a collection of common salts to survey
      the selectivity of the emission response. Phosphate and cyanide, representing the
      strongest anion binding to zinc(II), were detected even in the presence of other
      ions in tap water. Biologically relevant phosphates such as diphosphates and
      adenosine-5'-triphosphate (ATP) also produced a strong response. Because the
      binding constants with Zn(II) are very high, anion concentrations in the range of
      10(-6) to 10(-7) M are sufficient.

PMID- 22454838
TI  - Comparison friction: experimental evidence from medicare drug plans.
AB  - Consumers need information to compare alternatives for markets to function
      efficiently. Recognizing this, public policies often pair competition with easy
      access to comparative information. The implicit assumption is that comparison
      friction-the wedge between the availability of comparative information and
      consumers' use of it-is inconsequential because when information is readily
      available, consumers will access this information and make effective choices. We
      examine the extent of comparison friction in the market for Medicare Part D
      prescription drug plans in the United States. In a randomized field experiment,
      an intervention group received a letter with personalized cost information. That
      information was readily available for free and widely advertised. However, this
      additional step-providing the information rather than having consumers actively
      access it-had an impact. Plan switching was 28% in the intervention group, versus
      17% in the comparison group, and the intervention caused an average decline in
      predicted consumer cost of about $100 a year among letter recipients-roughly 5%
      of the cost in the comparison group. Our results suggest that comparison friction
      can be large even when the cost of acquiring information is small and may be
      relevant for a wide range of public policies that incorporate consumer choice.

PMID- 22454840
TI  - Abstracts of the CEM/IFEM (College of Emergency Medicine and International
      Federation for Emergency Medicine) Symposium. November 15-16, 2011. London,
      United Kingdom.

PMID- 22454839
TI  - Ligand binding assays in the 21st Century laboratory: platforms.

PMID- 22454841
TI  - Retraction: Pregnancy-related mortality in southern Nepal between 2001 and 2006:
      independent estimates from a prospective, population-based cohort and a direct
      sisterhood survey.

PMID- 22454842
TI  - Abstracts of the American Burn Association 44th Annual Meeting. April 24-27,
      2012. Seattle, Washington, USA.

PMID- 22454843
TI  - Abstracts of the 17th Congress of the Federation of Asian and Oceania Perinatal
      Societies (FAOPS) and the 16th Annual Congress of the Perinatal Society of
      Australia and New Zealand (PSANZ). March 18-21, 2012. Sydney, Australia.

PMID- 22454844
TI  - Abstracts of the 2nd Systemic Sclerosis World Congress. February 2-4, 2012.
      Madrid, Spain.

PMID- 22454845
TI  - Reinforcing properties of pups versus cocaine for fathers and associated central
      expression of Fos and tyrosine hydroxylase in mandarin voles (Microtus
      mandarinus).
AB  - The reciprocal interaction of pups and cocaine on reward effects in rodent
      mothers is known. However,it remains unclear whether such effects are apparent in
      father-offspring bonding. The mandarin vole (Microtus mandarinus) is a monogamous
      rodent with a high level of paternal care. We investigated the reinforcing
      properties of pups on vole fathers using a conditioned place preference paradigm
      across the postpartum period and looked for interactions and differences between
      the reinforcing effects of pups and cocaine. We also measured neuronal Fos and
      tyrosine hydroxylase (TH) expression underlying the preferences of fathers for
      pups or cocaine. Our data showed that fathers developed strong preferences for
      pups at various times (postnatal day 5-9, 13-17 and 19-23) without cocaine
      conditioning. Fathers showed a reduced preference for pups following simultaneous
      conditioning with cocaine. Although they preferred cocaine over postnatal day
      (PND) 5-9 pups, this preference was not detected for PND 13-17 pups. Fathers
      preferring cocaine exhibited an increase in Fos-immunoreactive neurons in the
      accumbens,medial nucleus of the amygdala, cingulate cortex, medial preoptic area
      and ventral tegmental area and had more TH-IR neurons in the ventral tegmental
      area compared to fathers preferring PND 5-9 pups. These results showed that
      similar to cocaine, mandarin vole pups elicit significant reward value to their
      fathers, but that paternal motivation is impaired by cocaine. A preference for
      cocaine over pups arose from the release of more dopamine and activation of a
      greater number of neurons within specific reward-associated neuronal subsets.

PMID- 22454846
TI  - CPB-K mice a mouse model of schizophrenia? Differences in dopaminergic,
      serotonergic and behavioral markers compared to BALB/cJ mice.
AB  - Schizophrenia is characterized by disturbances in social behavior, sensorimotor
      gating and cognitive function, that are discussed to be caused by a termination
      of different transmitter systems. Beside morphological alterations in cortical
      and subcortical areas reduced AMPA- NMDA-, 5-HT2-receptor densities and increased
      5-HT1-receptor densities are found in the hippocampus.The two inbred mouse
      strains CPB-K and BALB/cJ are known to display considerable differences in
      cognitive function and prepulse inhibition, a stable marker of sensorimotor
      gating. Furthermore, CPB-K mice exhibit lower NMDA-, AMPA- and increased 5-HT
      receptor densities in the hippocampus as compared to BALB/cJ mice. We
      investigated both mouse strains in social interaction test for differences in
      social behavior and with immuncytochemical approaches for alterations of
      dopaminergic and serotonergic parameters. Our results can be summarized as
      follows: compared to BALB/cJ, CPB-K mice showed:(1) significantly reduced
      traveling distance and number of contacts in social interaction test, (2)
      differences in the number of serotonin transporter-immunoreactive neurons and
      volume of raphe nuclei and a lower serotonergic fiber density in the ventral and
      dorsal hippocampal subfields CA1 and CA3, (3) no alterations of dopaminergic
      markers like neuron number, neuron density and volume in subregions of substantia
      nigra and ventral tegmental area, but a significantly higher dopaminergic fiber
      density in the dorsal hippocampus, the ventral hippocampus of CA1 and gyrus
      dentatus, (4) no significant differences in serotonergic and dopaminergic fiber
      densities in the amygdala.Based on our results and previous studies, CPB-K mice
      compared to BALB/cJ may serve as an important model to understand the interaction
      of the serotonergic and dopaminergic system and their impact on sensorimotor
      gating and cognitive function as related to neuropsychiatric disorders like
      schizophrenia.

PMID- 22454847
TI  - The effects of calorie restriction on operant-responding for alcohol in the
      alcohol preferring (iP) rat.
AB  - Calorie restriction (CR) is well established in the research literature to have
      several beneficial effects on health and has also been found to induce anxiolytic
      effects in the rat. Heightened levels of stress and anxiety are often regarded as
      key precipitating factors of relapse to substance abuse and alcohol addiction. In
      this study, the potential implication of a 25% CR diet in altering drug-seeking
      and relapse like behaviour through its capacity to influence anxiolytic-like
      behavioural changes was investigated.Anxiety was assessed in all rats with the
      elevated plus maze (EPM) and open field test prior to being trained to operantly
      self-administer either 10% ethanol, or water. Differences were found between the
      groups in the percentage of open arm/total arm duration and open arm/total arm
      entries in the EPM,demonstrating the anxiolytic effects of CR25%. Both control
      and CR25% groups showed preference for alcohol vs. water, however, controls
      responded more for alcohol during the conditioning phase than the CR25% group.
      Controls exhibited an alcohol deprivation-effect (ADE) post abstinence, and a cue
      induced reinstatement of alcohol-seeking post extinction however the CR25% did
      not. These results demonstrate that the anxiolytic effects of CR25% reduces
      operant responding for ethanol and inhibits relapse behaviour.Taken collectively,
      the results of this study suggest that in line with past research a CR25% dietary
      regime can induce anxiolytic effects in the alcohol preferring (iP) rat.
      Furthermore, it also reduces the intake of ethanol and inhibits the ADE and cue
      induced relapse that is characteristic of addiction in this strain.

PMID- 22454848
TI  - Frontiers in cardiovascular biology. Abstracts of the Second Congress of the ESC
      Council on Basic Cardiovascular Science. March 30-April 1, 2012. London, United
      Kingdom.

PMID- 22454849
TI  - Abstracts of the 19th European Congress of Psychiatry.

PMID- 22454851
TI  - [2012 French-Speaking Neurology Meeting. Abstracts].

PMID- 22454850
TI  - Diabetes and renal disease: two diseases one person. Guest editorial.

PMID- 22454852
TI  - [New actions of macrolides: general topics. Summary of discussion (1)].

PMID- 22454853
TI  - [New Actions of macrolides. General topics. Summary of discussion. (2)].

PMID- 22454854
TI  - [Inflammatory cells and cytokines involved in physiopathology and progression of
      influenza H5N1].

PMID- 22454855
TI  - [Description of the mechanism of influenza encephalopathy development].

PMID- 22454856
TI  - [Effects of macrolides in preventing influenza and airway inflammation].

PMID- 22454857
TI  - [Macrolide therapy of influenza and xanthine oxidase].

PMID- 22454858
TI  - [Progression of influenza. Summary of discussion].

PMID- 22454860
TI  - The new journal.

PMID- 22454859
TI  - [Mechanism of active enzyme formation by xanthine oxidase].

PMID- 22454861
TI  - Another drug interaction.

PMID- 22454862
TI  - Blood level or pharmacological response?

PMID- 22454863
TI  - The effect of indoramin on peripheral blood flow.
AB  - 1 The effect of indoramin, a new hypotensive agent, on peripheral blood flows of
      six normal subjects was determined and compared to placebo in a double-blind,
      randomized study. 2 Indoramin (0.25 mg/kg), administered intravenously, resulted
      in an increased forearm muscle volume as measured by strain gauge plethysmography
      and an increase in the skin temperature of the hand but not to the skin of the
      chest. 3 It is concluded that these effects are the result of alpha-adrenoceptor
      blockade.

PMID- 22454864
TI  - Observations on the effect of beta-adrenoceptor blocking drugs on glyceryl
      trinitrate tachycardia.
AB  - 1 The administration of 0.5 mg glyceryl trinitrate by chewing and keeping under
      the tongue increased heart rate in normal subjects in the supine and erect
      posture. 2 There was no significant difference between the responses in the same
      subject on repeated administration of glyceryl trinitrate on different days but
      there was a significant difference between the responses in different subjects. 3
      The oral administration of practolol and propranolol reduced the responses to
      glyceryl trinitrate. The two drugs progressively reduced the increase in heart
      rate produced by glyceryl trinitrate; there was no significant difference between
      their effects. Propranolol produced a significantly greater reduction than
      practolol in the maximum heart rate that was produced by glyceryl trinitrate. 4
      The administration of practolol (300 mg) twice daily by mouth to patients after
      an acute episode of ischaemic heart disease significantly reduced the increases
      in heart rate produced by standing and by glyceryl trinitrate in comparison to
      the responses in similar patients receiving a placebo.

PMID- 22454865
TI  - Some effects of Ko 1313 in animals and man.
AB  - 1 Ko 1313 competitively inhibited the increases in heart rate produced by
      isoprenaline in anaesthetized dogs. 2 Ko 1313 was 35 times more active than
      propranolol in blocking an isoprenaline induced tachycardia in anaesthetized dogs
      but only three times more active in blocking the increase in femoral blood flow
      produced by the injection of isoprenaline into the femoral artery. These
      observations suggest that Ko 1313 may have some cardio-selective activity. 3 When
      a series of doses of Ko 1313 was injected intravenously into anaesthetized dogs,
      the lower doses decreased heart rate while the larger doses increased heart rate.
      The same doses of propranolol reduced heart rate. 4 In lightly anaesthetized
      dogs, a series of doses of Ko 1313 progressively increased heart rate while
      propranolol produced little change. These observations indicate that Ko 1313 has
      slight intrinsic sympathomimetic activity. 5 The oral administration of Ko 1313
      and propranolol had no effect on resting heart rate in man but reduced the
      increases produced by head-up tilt, standing and exercise.

PMID- 22454866
TI  - Dose-response relationships in tropicamide-induced mydriasis and cycloplegia.
AB  - 1 Mydriatic and cycloplegic effects of tropicamide in the normal and in the
      guanethidine-treated human eye have been recorded following prolonged exposure of
      the eye to drug solutions. 2 Marked effects and satisfactory dose-response
      relationships were observed at drug concentrations within the range 1.25-40
      MUg/ml, by comparison with concentrations of 5-10 mg/ml usually applied as eye
      drops. 3 The findings are discussed in relation to drug concentrations which
      produce cholinergic antagonism in vitro.

PMID- 22454867
TI  - The effect of age on the hydroxylation of amylobarbitone sodium in man.
AB  - 1 Following a single oral dose of amylobarbitone sodium it has been shown that a
      group of young subjects convert a higher proportion of the dose to 3'
      hydroxyamylobarbitone than a group of elderly subjects. 2 Twenty-four hours after
      the administration of the drug, the mean plasma level of amylobarbitone in the
      elderly group is significantly higher than in the group of young subjects. 3 It
      is concluded that the rate of hydroxylation of amylobarbitone sodium decreases
      with age.

PMID- 22454868
TI  - Prescribing aids for gentamicin.
AB  - 1 A nomogram and a digital computer program have been developed to calculate
      dosage schedules of gentamicin for individual patients. The minimum input data
      consist of the patients' age, sex, body weight and serum creatinine
      concentration. 2 These prescribing aids have been evaluated in 36 patients with
      severe Gram negative infections. Renal function ranged from normal to complete
      anuria. Nomogram dosage schedules gave serum concentrations of gentamicin within
      the chosen therapeutic limits. Physician dosage schedules gave serum
      concentrations which sometimes exceeded and sometimes fell below these limits.
      The validity of the computer program was demonstrated by its ability to predict
      serum concentrations of gentamicin whatever the dosage schedule. 3 Half the
      patients recovered from the bacterial infection but seven remained infected and
      eleven died. Pseudomonas aeruginosa was the most difficult organism to eradicate.
      4 Four of the patients who survived developed ataxia and two developed hearing
      loss at high frequencies. The risk of ototoxicity was a function of mean trough
      serum gentamicin concentration and duration of treatment. Ototoxicity was only
      detected in patients with serum creatinine concentrations above 3 mg/100 ml who
      tended to have higher trough concentrations. When treatment was prolonged beyond
      8-10 days the risk of ototoxicity was increased without evidence of further
      substantial therapeutic benefit.

PMID- 22454869
TI  - Interaction between debrisoquine and phenylephrine in man.
AB  - 1 The interaction between phenylephrine and debrisoquine was studied using normal
      and hypertensive human volunteers, measuring blood pressure, pulse rate and pupil
      diameter. Single doses of phenylephrine were given before, during and after a
      short course of debrisoquine treatment. 2 The circulatory effects of
      phenylephrine are potentiated by debrisoquine; in a few subjects this
      potentiation was marked and a potential hazard. 3 Limited deductions could be
      made about the effects of debrisoquine on baroceptor responses and adrenergic
      mechanisms.

PMID- 22454870
TI  - Inhibition of phenytoin metabolism by sulthiame in epileptic patients.
AB  - 1 Measurements have been made of steady state serum phenytoin concentration,
      serum half-life of (14)C-labelled phenytoin, and the urinary ratio of the major
      metabolite of phenytoin to the unchanged drug (p-HPPH: DPH ratio) in epileptic
      patients on and off sulthiame therapy. 2 Starting sulthiame treatment produced an
      increase in serum phenytoin concentration, a prolongation of the half-life and an
      increase in the p-HPPH: DPH ratio. The total urinary output of phenytoin plus p
      HPPH was unaltered by sulthiame. 3 The results indicate that sulthiame or one of
      its metabolites inhibits the parahydroxylation of phenytoin by hepatic enzymes.

PMID- 22454871
TI  - Acute effects of varying doses of propranolol upon oxygen haemoglobin affinity in
      man.
AB  - 1 The effect of propranolol 2 h following doses of 10, 30, or 100 mg upon the
      blood oxygen-haemoglobin dissociation curves has been studied in four normal
      subjects. 2 The pO(2) at 50% saturation (p50) was not changed significantly under
      control conditions or after 10 and 100 mg doses. There was a just significant
      increase of 2 mmHg in the p50 value after the 30 mg dose. 3 There was no
      significant change in red cell adenosine triphosphate or 2,3-diphosphoglycerate
      nor in plasma phosphate. 4 There was no correlation between plasma propranolol
      concentration and changes in blood p50.

PMID- 22454872
TI  - Effects on the human central nervous system of two isomers of ephedrine and
      triprolidine, and their interaction.
AB  - 1 D(-)ephedrine is four times as potent as L(+)pseudoephedrine in producing both
      tachycardia and a rise in systolic blood pressure. No changes in diastolic blood
      pressure occurred in 12 subjects with doses of up to D(-)ephedrine (50 mg) and
      L(+)pseudoephedrine (180 mg). 2 Significant evidence of stimulation of the
      central nervous system occurred only after D(-)ephedrine in that tapping rates
      were increased and subjects could reliably detect that they had received an
      active drug. While mean performance rates in an auditory vigilance test were
      higher following both ephedrine isomers these changes were not significant. 3
      Impairment of both tapping rates and auditory vigilance occurred following
      triprolidine in another group of 12 subjects. The effect was generally related to
      dose of antihistamine given and lasted up to 7.25 hours. Subjective effects were
      reliably recognized by subjects following all treatments containing triprolidine
      (2.5 mg or more) for up to 4.75 hours. Using analogue lines for self rating the
      subjective effects following triprolidine indicated both mental and physical
      impairment differing significantly from scores after lactose and
      L(+)pseudoephedrine (60 mg). 4 Combination of triprolidine (2.5 mg) and
      L(+)pseudoephedrine (60 mg) produced effects similar to triprolidine alone on
      both subjective measures and the auditory vigilance test. It is suggested that
      these objective tests and subjective scales could be used to measure effects on
      the central nervous system produced by antihistamines together with similar
      drugs, and their interaction with other compounds administered concurrently.

PMID- 22454873
TI  - A simple technique for the rapid estimation of ethosuximide by gas liquid
      chromatography.

PMID- 22454874
TI  - Catecholamine excretion and pain.

PMID- 22454875
TI  - Propranolol on tests of visual function and central nervous activity.

PMID- 22454876
TI  - A simple spectrophotofluorometric method for the measurement of I.C.I. 66082 in
      plasma and urine.

PMID- 22454877
TI  - The renal excretion of mexiletine (Ko 1173) under controlled conditions of urine
      pH.

PMID- 22454878
TI  - Plasma concentrations of tricyclic antidepressive drugs.

PMID- 22454879
TI  - Interactions with warfarin.

PMID- 22454880
TI  - The clinical significance of indomethacin-probenecid interaction.
AB  - 1 The effect of the addition of probenecid to oral and rectal regimes of
      indomethacin was studied in three groups of rheumatoid arthritic patients. 2 The
      addition of probenecid increases plasma levels of indomethacin given both orally
      and rectally and significantly reduces the clinical parameters of joint
      inflammation. 3 The use of probenecid with indomethacin at night may be useful in
      reducing morning stiffness and pain. 4 Though indomethacin plasma levels are
      markedly raised during concurrent probenecid therapy remarkably few side effects
      were observed.

PMID- 22454881
TI  - Investigation of salbutamol tolerance.
AB  - 1 A double blind cross-over study was carried out on patients with reversible
      airways disease attending an out-patient clinic. 2 Twenty patients were given
      either salbutamol (200 MUg) or propellant by aerosol for two week periods and in
      another study twelve patients were given identical tablets containing either
      salbutamol (4 mg) or placebo for four week periods. Both forms of therapy were
      taken four times per day but stopped the evening before attending the clinic. 3
      The improvement in FEV(1) 10 min following salbutamol (200 MUg) by aerosol was
      measured after previous treatment with either salbutamol or placebo administered
      by aerosol and orally and the results were compared statistically. This failed to
      show a significant difference and suggests that regular treatment with salbutamol
      does not lead to a decreased response.

PMID- 22454882
TI  - The effect of different nebulizers with and without intermittent positive
      pressure breathing on the absorption and metabolism of salbutamol.
AB  - 1 The absorption and metabolism of [(3)H]-salbutamol have been studied to assess
      whether intermittent positive pressure breathing (IPPB) or a particular nebulizer
      have any advantages in delivering bronchodilator drugs to asthmatic patients. 2
      [(3)H]-salbutamol (10 mg) was given to asthmatic patients from either the Bird
      Mark 7 ventilator without intermittent positive pressure, the Bird micronebulizer
      attached to an electric air compressor, or the Wright's nebulizer attached to the
      same compressor. 3 All patients showed a high early plasma level of radioactivity
      due mainly to free salbutamol. This pattern suggests absorption from the lung and
      is similar to that seen after giving the drug from the Bird nebulizer using IPPB.
      4 In all cases less than 20% of the original dose was absorbed by the patient. 5
      Improvement in forced expiratory volume in one second (FEV(1)) was seen with all
      three treatments.

PMID- 22454883
TI  - A pilot study of orally administered Delta(1)-trans-tetrahydrocannabinol in the
      management of patients undergoing radiotherapy for carcinoma of the bronchus.
AB  - 1 Delta(1)-trans-tetrahydrocannabinol (Delta(1)-THC; 10 mg) or a placebo was
      given orally on 7 days to two groups of six patients on a cross-over pattern with
      7 days rest between. 2 The patients were hospitalized, suffering from inoperable
      bronchogenic carcinoma, subjected to radiation therapy, and anxious. 3 Self
      rating mood scales were filled in before, and 2 and 6 h after ingestion on the
      first and seventh day of medication. 4 Records of sleep, pain, general well
      being, temperature, cardiovascular and gastrointestinal parameters were kept. 5
      Delta(1)-THC caused drowsiness and improved night sleep, reduced pain, increased
      fatigue and confusion and reduced elation and vigour; it caused slight
      tachycardia and hypotension as also did placebo. 6 The effects of Delta(1)-THC
      were stronger after 2 h than 6 h and no tolerance had developed at 7 days. 7 The
      management of stressful patients was considered to have been improved by the
      drug.

PMID- 22454884
TI  - The effect of beta-adrenoceptor blockade on body temperature and plasma renin
      activity in heat-exposed man.
AB  - 1 The effect of propranolol (5 mg i.v.) on rectal and skin temperatures, heart
      rate, blood pressure, plasma renin activity (PRA) and plasma renin substrate
      concentration (PRS) was investigated in twelve men exercising in the heat. The
      effect of practolol (10 mg i.v.) on PRA was investigated in five men. 2 Body
      temperatures were insignificantly affected by propranolol, while heart rate
      elevation in response to exercise in the heat was 21% lower than in the same
      subjects receiving saline. Diastolic blood pressure during exercise was elevated
      by propranolol. 3 The normal increase in PRA seen in heat exposure was suppressed
      by propranolol to levels seen when the same exercise was carried out at 25
      degrees C. Practolol did not affect the renin response to heat exposure. 4 PRS
      was not altered significantly by exercise or heat. 5 The results indicate that
      the increase in PRA seen in the heat is largely a result of increased sympathetic
      activity.

PMID- 22454885
TI  - Effect of angiotensin-converting enzyme inhibitor on response of plasma renin
      activity and aldosterone to tilting in man.
AB  - 1 The effect of an angiotensin-converting enzyme inhibitor (SQ 20,881; 0.5 mg/kg)
      on the response to tilting of plasma renin activity (PRA), plasma aldosterone and
      cortisol was studied in five normal subjects. 2 PRA rose significantly in both
      the supine and upright positions following administration of SQ 20,881; no
      significant effect on aldosterone or cortisol was observed.

PMID- 22454886
TI  - Bioavailability of commercial tetracycline products.
AB  - 1 Thirteen commercial tetracycline products were assessed for bioavailability by
      in vitro and in vivo tests. Three failed the B.P. disintegration test and three
      products in a dissolution test released less than 50% of their stated potency by
      3 hours. 2 In vivo bioavailability was assessed by serum and urinary data. Six
      products were tested by serum data over 48 h and their bioavailability profiles
      varied but their ranking correlated well with in vitro dissolution in water;
      three were better than the others. In a further study, based on urinary excretion
      alone, the thirteen products showed considerable variation in bioavailability.
      One product gave an extremely poor result (6 mg excreted in 24 hours). 3 These
      findings of generic non-equivalence illustrate the need for adequate standards of
      bioavailability testing.

PMID- 22454887
TI  - Some clinical implications of the protein binding of digoxin.
AB  - 1 The binding of [(3)H]-digoxin to human plasma proteins was studied using both
      ultrafiltration and frontal analysis, to establish a suitable method for the
      measurement of digoxin-protein interaction, and to assess the effect of
      variations in digoxin protein binding on its distribution. 2 Using
      ultrafiltration, [(3)H]-digoxin was found to bind to plasma proteins to the
      extent of 30-40% over a concentration range of 0.001-1 ng/ml. Frontal analysis
      was unsuccessful in the measurement of digoxin protein binding. 3 Dilution
      experiments using plasma and human serum albumin suggested that variations in
      digoxin protein binding would be unlikely to cause significant alterations in the
      levels of free drug in the body. 4 The possible clinical implications of these
      results are discussed.

PMID- 22454888
TI  - Bioavailability of digoxin from rapidly dissolving preparations.
AB  - 1 Intestinal absorption of digoxin was assessed by determination of peak plasma
      concentrations, areas under plasma concentration curves over 80 h, and 10 day
      urinary excretion. Absorption was equal after ingestion of single doses of
      standard Lanoxin (Wellcome) tablets, tablets and capsules of ultra-rapid
      dissolution rate material, or an oral solution of digoxin in water. 2 Mean plasma
      concentrations and dosage-interval urinary excretion were highly similar during
      14 day courses of either Lanoxin or ultra-rapid dissolution tablets. Increased
      bioavailability does not result from encapsulation of solid dosage presentations,
      nor from increasing tablet dissolution rate beyond 75% in 15 minutes. 3 Fourteen
      day courses of tablets of slow dissolution rate produced lower and less
      consistent mean plasma concentrations and urinary excretion. Slow dissolution
      rates are associated with greater individual variability in absorption.

PMID- 22454889
TI  - Effect of diazepam on oculomotor balance.

PMID- 22454890
TI  - The effect of fluphenazine on steady state plasma levels of nortriptyline.

PMID- 22454891
TI  - Proceedings of the British Pharmacological Society Clinical Pharmacology Section:
      Edinburgh, 11th-12th July, 1974.

PMID- 22454893
TI  - Sequential procedures in perspective.

PMID- 22454894
TI  - The assessment of beta-adrenoceptor blocking drugs in hyperthyroidism.
AB  - 1 Intravenous propranolol and practolol both reduced resting supine heart rate in
      patients with hyperthyroidism. Propranolol produced a significantly greater
      reduction than practolol, which did not have a dose-dependent effect. 2 The
      effect of these drugs on resting heart rate was much less than their effect on
      the tachycardias produced both by severe exercise and by standing upright in
      hyperthyroid patients. Propranolol again produced a significantly greater
      reduction than practolol in each situation, but practolol did have a dose
      dependent effect on exercise heart rate. 3 The percentage reduction of standing
      tachycardia produced by the two drugs appeared to parallel closely the reduction
      in exercise tachycardia. 4 It is concluded that a simple and convenient way of
      assessing the activity of beta-adrenoceptor blocking drugs in hyperthyroid
      patients would be to measure their effect on the tachycardia induced by standing.
      Their effect on resting heart rate should not be used. 5 Practolol may be useful
      in the management of hyperthyroidism in patients in whom propranolol and similar
      non-selective beta-adrenoceptor blocking drugs are contraindicated.

PMID- 22454895
TI  - Availability of methaqualone from commercial preparations: in vitro and in vivo
      studies in man.
AB  - 1 The plasma profiles of methaqualone obtained from different commercially
      available preparations have been compared. Tablets were absorbed more efficiently
      than capsules. Mandrax preparations achieved much higher plasma levels than
      Melsedin tablets or the Melsed or Sedaquin capsules. These differences appear to
      be due to formulation factors. 2 The efficacy of the different drugs as hypnotics
      corresponded well with the blood levels achieved. 3 There was a significant
      correlation between the in vitro l/t(50%) and the in vivo peak plasma levels.
      Thus in vitro dissolution studies can be used to predict the efficiency of
      absorption of different formulations in man.

PMID- 22454896
TI  - Purine and pyrimidine excretion in psoriasis: a comparison with healthy controls
      during allopurinol therapy.
AB  - 1 Urinary purine excretion has been investigated in two healthy controls and two
      patients with psoriasis, one a hyperuricaemic, one a normouricaemic. No
      difference was detected between the patients and controls. Therapy with
      allopurinol effectively lowered blood and urinary uric acid levels and produced a
      deficit in total urinary oxypurine excretion in both controls and patients with
      psoriasis. The concomitant increase in xanthine excretion was greater than the
      increase in hypoxanthine excretion and xanthine/hypoxanthine ratios (average 0.70
      and 1.0 prior to therapy) were increased by allopurinol to an average of 3.0 and
      3.8 respectively in the two groups. Allopurinol also reduced the excretion of 8
      hydroxy-7-methyl guanine but no effect on the excretion levels of other minor
      purine bases was noted. 2 Allopurinol was metabolized similarly by both patients
      and controls, 84% of the administered allopurinol being accounted for as urinary
      metabolites. 74% of the drug in the urine was excreted as oxipurinol, 26% as
      unchanged allopurinol plus allopurinol riboside, the remainder being oxipurinol
      riboside. 3 Pseudouridine excretion in 25 healthy controls was 86.5 +/- 17.8
      mg/24 hours. Pseudouridine excretion was not excessive in the patients with
      psoriasis and was not altered by allopurinol therapy. 4 No abnormality or
      difference in purine or pyrimidine excretion in either patient was detected prior
      to or during therapy which could be related to the epidermal lesion.

PMID- 22454897
TI  - The assessment of potential drug interactions with a new tricyclic antidepressant
      drug.
AB  - 1 Methods for the investigation of possible interactions with tricyclic
      antidepressant drugs are described. These methods have been applied to a new
      compound, Ciba 34276-Ba, which has been shown to have antidepressant activity. 2
      In five normal volunteers tested before and during treatment with Ciba 34276-Ba,
      no abnormalities of resting or post-exercise electrocardiographs occurred. A
      three-fold reduction in tyramine-responsiveness was seen in three normal subjects
      studied, but no potentiation of the noradrenaline pressor effect occurred. One of
      six patients given Ciba 34276-Ba whilst on long-term treatment with bethanidine
      showed loss of blood pressure control. 3 The metabolic clearance of antipyrine
      was unaltered in two subjects studied, showing no evidence of induction or
      inhibition of hepatic microsomal oxidizing enzymes by Ciba 34276-Ba.

PMID- 22454898
TI  - Thiopurinol: comparative enzyme inhibition and protein binding studies with
      allopurinol, oxipurinol and 6-mercaptopurine.
AB  - 1 The metabolites of thiopurinol have been investigated in intact human and pig
      erythrocytes using [6-(14)C]-thiopurinol, high voltage electrophoresis and
      automated cation exchange chromatography. 2 Pre-incubation of human erythrocytes
      in vitro with thiopurinol increased the formation of hypoxanthine from [8-(14)C]
      inosine and simultaneously reduced IMP synthesis. 3 Reduced inosine formation,
      following one week of thiopurinol therapy, has also been observed in vitro using
      the intact red cells from three patients suffering from gout. 4 Binding of
      thiopurinol, and to lesser extents of 6-mercaptopurine, uric acid, oxipurinol and
      allopurinol, has been demonstrated electrophoretically to human and pig serum
      proteins. 5 Thiopurinol is shown to have a greater binding capacity for purified
      human serum albumin than uric acid or 6-mercaptopurine at varying substrate and
      albumin concentrations covering the physiological range. Under these conditions
      the binding of uric acid is reduced in the presence of thiopurinol. 6 A
      comparison of the distribution of thiopurinol, 6-mercaptopurine, allopurinol and
      oxipurinol in whole blood has revealed that allopurinol and oxipurinol are not
      irreversibly bound to cellular proteins; whereas 30% and 13% of the total
      cellular uptake was irreversibly bound in the case of thiopurinol and 6
      mercaptopurine respectively at substrate levels of 1 nmol per MUl blood.

PMID- 22454899
TI  - Metabolism of terbutaline in man and dog.
AB  - 1 The metabolism of terbutaline (1-(3,5-dihydroxyphenyl)-2-tertiarybutylamino
      ethanol), a drug which acts selectively on beta(2)-adrenoceptors has been studied
      in man and dog. 2 The sulphate conjugate of terbutaline was the only metabolite
      identified in plasma or urine from humans or dogs given the drug either orally or
      intravenously. We have confirmed that terbutaline, a resorcinol derivative, is
      not a substrate for catechol-0-methyl transferase in man or dog. 3 Metabolism of
      terbutaline was dependent upon the route of administration in man, but not in
      dog. In man, oral terbutaline was largely conjugated whereas drug administered
      intravenously appeared largely unchanged in urine. 4 Conjugation of oral
      terbutaline, which probably occurred during the 'first-pass' through the gut wall
      or liver, was less than oral isoprenaline. This may explain why the poorly
      absorbed terbutaline is a more effective oral bronchodilator than isoprenaline,
      even though the latter drug is completely absorbed following oral dosing.

PMID- 22454900
TI  - Effects of food and exercise on the absorption of effervescent aspirin.
AB  - 1 The absorption of effervescent aspirin was studied in normal volunteers of both
      sexes under varied conditions of activity in both fasting and non-fasting states.
      2 Moderate activity resulted in no significant changes in absorption compared
      with that at rest. 3 In non-fasting subjects the absorption was reduced but this
      reduction was attenuated with time until after 60 min the plasma levels were
      similar. 4 There was no interaction between the resting/non-resting and
      fasting/non-fasting absorption.

PMID- 22454901
TI  - Ro 3-4787, a new beta-adrenoceptor blocking agent: Studies in normal volunteers.
AB  - 1 A new beta-adrenoceptor blocking agent, Ro 3-4787, was administered orally to
      resting subjects. Peak levels of 106.2 +/- 15.5 ng/ml were reached after 20 mg
      given in the fasting state. After intravenous administration, an inverse
      rectilinear relationship was shown between the log dose (2 mg-20 mg) and the
      heart rate during vigorous exercise on a bicycle ergometer. 2 A double-blind
      study in five normal subjects using 0.03 mg/kg and 0.15 mg/kg showed that
      propranolol and Ro 3-4787 were equally effective in reducing the exercise heart
      rate. There was an inverse correlation between the log plasma level before
      exercise and the heart rate during exercise for both drugs over the range
      studied.

PMID- 22454902
TI  - Indomethacin or amylobarbitone sodium for sleep in rheumatoid arthritis, with
      some observations on the use of sequential analysis.
AB  - 1 A double blind crossover trial in patients with rheumatoid arthritis showed
      that indomethacin given at night was superior to a hypnotic in providing sleep
      and relieving morning stiffness. 2 In a second trial, the combination of a
      hypnotic with indomethacin was not superior to indomethacin alone as judged by
      patients' preference, but further analysis suggested that the combination
      improved sleep without affecting morning stiffness. 3 It is argued that the use
      of a small closed sequential design produced too small a sample in the first
      trial. In the second trial, the sample was relatively large but the result was
      inconclusive; measurement of the response in terms of preference alone obscured
      the effect of treatment on one aspect of the symptomatology studied.

PMID- 22454903
TI  - Rate of elimination of tracer doses of phenytoin at different steady-state serum
      phenytoin concentrations in epileptic patients.
AB  - 1 Serum phenytoin concentration, the serum half-life of a tracer dose of carbon
      labelled phenytoin, and the ratio of the major metabolite of phenytoin to
      unchanged drug in urine (p-HPPH: DPH ratio) were measured in epileptic patients
      on chronic anticonvulsant therapy. 2 A significant correlation was found between
      serum phenytoin concentration and half-life, the slope of the regression line
      being dose dependent. 3 A significant negative correlation was found between
      serum phenytoin concentration and p-HPPH: DPH ratio. 4 Increasing the daily dose
      of phenytoin lead to a lengthening of the half-life and a reduction in the p
      HPPH: DPH ratio. The reverse occurred on lowering the dose. 5 These changes
      indicate that phenytoin hydroxylation is saturable. 6 Difficulty in achieving a
      stable serum phenytoin concentration within the therapeutic range may result.

PMID- 22454904
TI  - Phenytoin dose adjustment in epileptic patients.
AB  - 1 A preliminary survey showed that many outpatients with partially controlled
      epilepsy had serum concentrations of phenytoin below the recommended therapeutic
      range (10-20 MUg/ml). A phenytoin tolerance test was devised with the intention
      of predicting a more adequate daily dose for such a patient. 2 Fifteen patients
      were each given an oral test dose of 600 mg phenytoin sodium and the serum
      concentration of phenytoin was measured at intervals over 48 h; the concentration
      rose during the first 4 h and decayed between 12-48 h as an almost linear
      function of time. 3 The serum concentration/time curves were fitted by an
      interative computer program based on the Michaelis-Menten equation. The mean
      saturated rate of elimination of phenytoin was 435 mg/day and the serum
      concentration (K(m)) corresponding with 50% saturation was 3.8 MUg/ml. The mean
      calculated dose of phenytoin sodium required for a steady state serum
      concentration of 10-20 MUg/ml was 345-400 mg/day. 4 The Michaelis-Menten
      principle was used to predict steady state serum phenytoin concentrations in
      individual patients receiving daily doses of phenytoin sodium adjusted by steps
      of 100 mg. The serum concentrations tended to be either too low or too high. The
      steep relationship between phenytoin concentration and dose indicates that when
      the concentration reaches 5-10 MUg/ml it is then appropriate to adjust dose by
      small steps of about 25 mg.

PMID- 22454905
TI  - Some preliminary observations on ICI 58 834, a new psychotropic agent, in man.

PMID- 22454906
TI  - Enterohepatic circulation of practolol in man.

PMID- 22454907
TI  - Proceedings of the British Pharmacological Society Clinical Pharmacology Section:
      London, 2-4 January, 1974.

PMID- 22454910
TI  - Propranolol, anxiety and the central nervous system.

PMID- 22454911
TI  - Lithium treatment strongly inhibits choline transport in human erythrocytes.
AB  - 1 The influx of [(14)C]-choline and the efflux of (22)Na in human erythrocytes
      were measured in vitro using blood from patients treated with lithium, patients
      not on lithium and healthy individuals. 2 The administration of lithium to
      patients significantly reduces the transport of choline; during the first 6 weeks
      of treatment the influx of choline is about half the normal rate, later it falls
      to around 10%. 3 This inhibition of choline transport is not dependent on the
      presence of lithium in the incubation medium. 4 The active and passive efflux of
      sodium are apparently not affected by lithium treatment.

PMID- 22454912
TI  - A pharmacokinetic interaction in man between phenobarbitone and fenoprofen, a new
      anti-inflammatory agent.
AB  - 1 The effect of repeated administration of phenobarbitone on the plasma
      disposition of fenoprofen (+/--2-(3-phenoxyphenyl) propionic acid) was
      investigated in rats and man. 2 The plasma elimination rate constants increased
      significantly and the rats excreted proportionately more metabolized fenoprofen
      in the urine. These findings are consistent with an increase in the rate of
      metabolism of fenoprofen. 3 This interaction between phenobarbitone (and
      presumably other inducers of drug metabolizing enzymes) and fenoprofen should be
      considered when evaluating the clinical usefulness of fenoprofen.

PMID- 22454913
TI  - A controlled trial of practolol in mild hypertension.
AB  - 1 Fifteen patients with diastolic blood pressures between 90 and 120 mmHg were
      admitted to a trial comparing placebo with practolol at doses up to 500 mg 12
      hourly. 2 The trial was a double blind cross over study. Treatments were
      allocated at random and each treatment block lasted 12 weeks. 3 Ten patients
      completed the trial, and none of those who withdrew experienced serious unwanted
      effects. 4 Practolol caused significant falls in standing systolic and diastolic
      pressures and the supine diastolic pressure.

PMID- 22454914
TI  - Physiological and psychological effects of +/--propranolol, +-propranolol and
      diazepam in induced anxiety.
AB  - 1 Four equal-sexed groups of eight normal subjects were given single doses of
      either (+/-)-propranolol (120 mg), (+)-propranolol (120 mg), diazepam (6 mg) or
      placebo using double-blind procedure and their effects studied under three types
      of experimental stress and at rest. 2 Finger tremor, EEG, averaged auditory
      evoked response, skin conductance, heart rate and respiratory rate were measured
      at each time of testing, and subjects also completed performance tests (reaction
      time, tapping speed and symbol copying) and subjective mood scales. 3 Neither (+)
      nor (+/-)-propranolol had any beneficial effects on mood and physiological tests
      showed that, although adequate beta-adrenoceptor blockade was achieved, there was
      no evidence of sedation. 4 Diazepam reduced subjective anxiety, significantly
      lessened the main amplitude of the auditory evoked response and also reduced the
      proportion of slower rhythms in the EEG. 5 The results suggest that (+)- and (+/
      )-propranolol have no psychotropic effects on induced anxiety and that their
      modes of action are fundamentally different from that of diazepam.

PMID- 22454915
TI  - Physiological response to propranolol and diazepam in chronic anxiety.
AB  - 1 Twelve chronically anxious psychiatric out-patients, comprising six with
      somatic anxiety and six with psychic anxiety, were treated with (+/-)
      propranolol, diazepam and placebo for one week each in flexible dosage using a
      balanced cross-over experimental design. 2 After each treatment, in addition to
      ratings completed by patient and psychiatrist, finger tremor, EEG, averaged
      auditory evoked response, skin conductance, heart and respiratory rate were
      measured. 3 Diazepam significantly increased the amount of fast activity (13.5-26
      Hz) in the EEG but produced few peripheral effects apart from a reduction in
      finger tremor. 4 Propranolol had no central physiological effects but reduced
      both pulse rate and finger tremor. 5 The physiological effects of propranolol in
      chronic anxiety are different from those of diazepam and therapeutic benefit
      appears to be due to a direct effect on certain somatic symptoms.

PMID- 22454916
TI  - The clinical pharmacology of salmefamol.
AB  - 1 The absorption, excretion and metabolism of [(3)H]-salmefamol, a new
      sympathomimetic bronchodilator drug, have been studied in asthmatic patients. 2
      Following oral administration of 1 or 2 mg to four patients the drug was well
      absorbed, peak plasma levels occurring from 0.6-2.0 h after administration. An
      improvement in forced expiratory volume in 1 s (FEV(1)) (ranging from 12-50%
      above baseline) was seen. 3 Following aerosol administration of 0.22-0.34 mg to
      four patients a rapid rise in FEV(1) was seen (range 26-117%). The plasma and
      urinary pictures following this route were similar to those seen after oral
      administration, suggesting that the majority of the dose was swallowed. 4 Very
      little free salmefamol was found in plasma or urine, the majority being present
      as metabolites. Urinary radioactivity was mainly present in the form of sulphate
      conjugates of at least two compounds, one of which was salmefamol. The other
      compound has not been identified but it is suggested that it may be an active
      metabolite.

PMID- 22454917
TI  - A comparison of the effects of prostaglandin E(2) and salbutamol by intravenous
      infusion on the airways obstruction of patients with asthma.
AB  - 1 The effects of intravenous infusion of prostaglandin E(2) (PGE(2)) on forced
      expiratory volume in 1 second (FEV(1)) were studied in ten asthmatic patients and
      compared with the effects of intravenous salbutamol. 2 PGE(2) at infusion rates
      of 5, 10 and 20 MUg/min for three 15 min periods resulted in a small
      bronchodilator effect in four patients, bronchoconstriction in four, and had no
      measurable effect on FEV(1) in two patients; side effects were frequent and it
      was concluded that PGE(2) was unsuitable for use in the management of attacks of
      asthma. 3 In the same subjects bronchodilatation occurred during infusion of
      salbutamol at flow rates of 5, 10 and 20 MUg/min (six patients), 10, 20 and 40
      MUg/min (two patients) and 20, 40 and 80 MUg/min (two patients). Serious
      cardiovascular effects were not encountered at flow rates of less than 20
      MUg/minute.

PMID- 22454918
TI  - Biological availability and in vitro dissolution of oxytetracycline dihydrate
      tablets.
AB  - 1 The concentration of oxytetracycline in plasma was studied by microbiological
      assay after oral administration of four different preparations of oxytetracycline
      dihydrate tablets. 2 There were statistically significant differences in
      biological availability between the four preparations, as assessed by the peak
      plasma level, the area under the plasma concentration-time curve, or the
      cumulative fraction of the dose excreted in urine at 405 minutes. In contrast,
      differences between the subjects were not statistically significant. 3 The
      differences in biological availability were not predictably related to the in
      vitro dissolution of the tablets.

PMID- 22454919
TI  - The influence of elevated plasma hydrocortisone concentrations on antipyrine
      metabolism in man.
AB  - 1 The plasma half-life of antipyrine was estimated overnight in four healthy
      volunteers on two separate occasions, one during i.v. infusion of hydrocortisone
      (3 mg/h) and the second during an infusion of normal saline. 2 The plasma
      fluorogenic corticosteroid concentration averaged 12.5 MUg/100 ml during saline
      infusion, increasing to 20.1 MUg/100 ml during hydrocortisone infusion. 3 The
      mean antipyrine half-life increased from 9.7 h during saline infusion to 12.6 h
      during hydrocortisone infusion. 4 No consistent change was found in the apparent
      volume of distribution or urinary excretion of antipyrine, or of the urinary
      excretion of D-glucaric acid. 5 The stimulation by hydrocortisone of antipyrine
      metabolism demonstrated by other workers has not been found.

PMID- 22454920
TI  - A preliminary study of the effect of norfenfluramine on lipogenesis by human
      adipose tissue in vitro.
AB  - 1 Norfenfluramine is thought to be the major active metabolite of fenfluramine in
      man. Therefore its in vitro effect on lipogenesis in human adipose tissue from
      twelve patients was investigated. 2 Although inhibition of lipogenesis was
      demonstrated, the concentrations of norfenfluramine necessary (>1 mM) were much
      higher than normal blood levels of the drug. 3 There was no correlation between
      the degree of inhibition by norfenfluramine in vitro and fat cell size, age or
      relative weight of the subject. Greater degrees of inhibition were however
      associated with samples of tissue from patients with higher blood glycerol
      concentrations and lower blood triglyceride concentrations.

PMID- 22454921
TI  - The absorption and metabolism of a standard oral dose of levodopa in patients
      with Parkinsonism.
AB  - 1 The metabolism of a standard oral dose of levodopa was studied in forty-two
      patients with Parkinsonism. Plasma levodopa and 3-o-methyldopa concentrations
      were estimated at intervals for 8 h after ingestion and the concentration of
      homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) was measured at 8
      hours. Clinical responses 3 months after the test were compared with these
      findings. 2 Although therapeutic benefit correlated significantly with calculated
      estimates of both plasma levodopa concentration and CSF HVA at optimal levodopa
      dose, individual values were widely scattered. There was no significant
      correlation between toxic effects and plasma levodopa or CSF HVA; and 3-o
      methyldopa concentrations similarly did not show a significant correlation with
      either toxic or therapeutic effects. 3 Blood and CSF levels of levodopa or the
      metabolites measured in this study were not significantly altered by concurrent
      treatment with either anticholinergic drugs or amantadine nor by previous
      treatment with levodopa.

PMID- 22454922
TI  - The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide
      metabolites in a large population of chronic schizophrenics.
AB  - 1 Blood samples were obtained from eighty-six chronic schizophrenics receiving a
      wide range of oral doses of chlorpromazine. Plasma concentrations of
      chlorpromazine, 7-hydroxychlorpromazine and chlorpromazine sulphoxide were
      estimated using a sensitive gas-liquid chromatographic method and their
      relationships to oral dose and to global clinical control were investigated.2
      Wide variability was observed in the plasma concentrations of unchanged drug and
      metabolites between patients receiving similar daily doses.3 In general the
      plasma concentrations of the 7-hydroxy and sulphoxide metabolites were of similar
      magnitude to the concentrations of chlorpromazine.4 Global symptom control was
      unrelated to the plasma concentration of unchanged chlorpromazine. However,
      patients judged to be under good control had relatively higher concentrations of
      the biologically active 7-hydroxy metabolite in their plasma than patients who
      were poorly controlled and in whom the biologically inactive sulphoxide
      metabolite predominated. When the ratio of 7-hydroxychlorpromazine to
      chlorpromazine sulphoxide was derived for each patient, a highly significant
      difference was found to exist between the metabolite ratios of patients grouped
      according to clinical control.5 It is suggested that a prediction of therapeutic
      response to chlorpromazine may be provided in the form of the ratio of the plasma
      concentration of biologically active metabolite to the concentration of either
      the unchanged drug or its inactive metabolite.

PMID- 22454923
TI  - The clinical pharmacology of viloxazine hydrochloride-a new anti-depressant of
      novel chemical structure.
AB  - 1 The clinical pharmacological properties of viloxazine hydrochloride (ICI
      58,834, Vivalan), a new antidepressant of novel chemical structure, have been
      investigated in a series of double-blind randomized studies comparing it with
      placebo and imipramine. Throughout the studies, viloxazine hydrochloride was
      given in single doses of 100 mg (expressed as base), and imipramine hydrochloride
      was given in single doses of 50 mg (expressed as salt). 2 The effect of
      viloxazine upon the following parameters was measured: pulse rate, blood
      pressure, forced expiratory volume, reaction time, critical flicker frequency,
      salivary flow, pupil size and palpebral fissure size. In addition, the possible
      interaction between viloxazine and alcohol was investigated using measurements of
      reaction time. 3 Both viloxazine and imipramine produced a transient tachycardia,
      but no consistent effect on blood pressure was seen. Neither drug had any effect
      upon forced expiratory volume. 4 The differences that emerged between viloxazine
      and imipramine were that viloxazine depressed critical flicker frequency whereas
      imipramine did not, and imipramine prolonged reaction time whilst viloxazine did
      not. Imipramine reduced salivary flow and increased the size of the pupil and
      palpebral fissure. Viloxazine did neither. 5 Imipramine was shown to potentiate
      alcohol whereas, at the doses used, viloxazine did not. 6 It is concluded that
      viloxazine appears to have less anticholinergic and possibly less sympathomimetic
      properties than imipramine. It is also concluded that viloxazine, unlike
      imipramine, does not potentiate alcohol.

PMID- 22454924
TI  - Serum concentration and urinary excretion of uric acid following piribedil (ET
      495).

PMID- 22454925
TI  - The distribution of propranolol between blood and plasma in hypertensive
      patients.

PMID- 22454926
TI  - Dialysis of drugs in vitro.

PMID- 22454928
TI  - Continuing education and clinical pharmacology.

PMID- 22454929
TI  - Drugs and driving.

PMID- 22454930
TI  - Correlation between plasma quinidine and cardiac effect.
AB  - 1 The relationship between serum quinidine levels and rate-corrected QT (QTc)
      interval after administration of single identical doses of quinidine was
      assessed. Quinidine concentrations were determined by a modification of Hamfelt &
      Malers' (1963) method. The significance and clinical application of our findings
      is discussed. 2 Individual responses (both in quinidine concentration and QTc
      prolongation) were variable, though the variation was no greater with QTc
      prolongation response than with serum quinidine levels. A significant peak in QTc
      prolongation occurred after quinidine administration and this was not accompanied
      by a similar peak in quinidine levels. There was some correlation (r = 0.53)
      between serum quinidine levels and QTc interval but a better correlation was
      found between rate of rise of quinidine concentration and QTc prolongation (r =
      0.87). 3 One individual showed marked QTc prolongation with slow rate of rise of
      quinidine levels. Red cell quinidine levels were lower in this individual and he
      may be showing increased myocardial sensitivity to quinidine.

PMID- 22454931
TI  - Comparison of the therapeutic effectiveness of aprindine, procainamide and
      quinidine in chronic ventricular dysrhythmias.
AB  - 1 A cross-over study with aprindine (100 mg daily after a loading dose of 200
      mg), procainamide (4 * 1000 mg daily) and quinidine bisulphate (2 * 750 mg
      daily), all given orally, was performed in seventeen patients with stable chronic
      premature ventricular contractions following healed myocardial infarction. 2 The
      effectiveness of the treatment was evaluated during three consecutive weeks by
      continuous ambulatory tape recording of the electrocardiogram and repeated
      determinations of plasma levels were done. 3 The results showed that aprindine
      was more effective than procainamide and quinidine. 4 For the three drugs the
      therapeutic plasma levels varied markedly from patient to patient, but for each
      patient taken individually, the therapeutic activity could be correlated with the
      plasma levels.

PMID- 22454932
TI  - Acetylation of procaine amide in man studied with a new gas chromatographic
      method.
AB  - 1 A specific gas-chromatographic method was developed for determination of N
      acetylprocaine amide in plasma and urine, using 4-amino-N-(2
      piperidinoethyl)benzamide as an internal standard. The investigation was
      performed in 50 cardiac patients who had reached steady-state plasma
      concentrations of procaine amide. 2 The plasma concentrations of the acetylated
      metabolite varied between 1.0 and 15.0 MUg/ml and were thus of the same order of
      magnitude as those of the parent drug. Especially high plasma levels of the
      metabolite were seen in patients with poor kidney function. 3 The urinary
      excretion of the metabolite varied markedly between individuals and ranged
      between 6 and 52% of the administered daily dose. There was a clear tendency
      towards higher rates of acetylation of procaine amide in patients with short
      plasma half-lives of isoniazid, i.e. the phenotype rapid acetylators. Because of
      coexisting therapy with other drugs and impaired renal function in some patients
      studies are required in healthy human volunteers to ascertain whether the
      acetylation of procaine amide and isoniazid are mediated by the same enzyme
      system.

PMID- 22454933
TI  - Acute effect of antipyretic analgesics, alone or in combination with alcohol, on
      human psychomotor skills related to driving.
AB  - 1 The effect of acetylsalicylic acid (1 g), indomethacin (50 mg), and
      phenylbutazone (200 mg) on psychomotor skills was examined double blind on 180
      volunteer students. Ninety students received ethyl alcohol (0.5 g/kg) and 90
      subjects an equal volume of placebo drink in combination with the drugs. 2
      Psychomotor skills were measured with a choice reaction test, two co-ordination
      tests, and a divided attention test, having correlation with traffic behaviour.
      The subjects assessed their feelings of performance by means of a rating scale.
      The tests were done 30, 90 and 150 min after the administration of the agents. 3
      Acetylsalicylic acid proved inactive whereas both indomethacin and phenylbutazone
      impaired eye-hand co-ordination and divided attention. Acetylsalicylic acid did
      not interact with alcohol to a measurable extent whereas indomethacin in
      combination with alcohol proved less harmful than without it. The deleterious
      effects of phenylbutazone and alcohol were additive. 4 An impairment of
      psychomotor skills related to driving by indomethacin and phenylbutazone should
      be considered when prescribing these drugs to active out-patients.

PMID- 22454934
TI  - The effect of frusemide on indomethacin plasma levels.
AB  - 1 The pharmacokinetic and clinical effects of concurrent oral indomethacin and
      frusemide administration were determined in eight patients with rheumatoid
      arthritis. 2 Oral frusemide significantly reduces the plasma level of
      indomethacin following concurrent administration of the two drugs orally. 3 A
      profile of pain index, articular index and grip strength following oral
      indomethacin (50 mg) was determined and although the decrease in articular index
      was less when frusemide and indomethacin were given together it did not reach
      statistical significance.

PMID- 22454935
TI  - The alimentary absorption of diamorphine and morphine in man as indicated by
      urinary excretion studies.
AB  - 1 Urine was collected over 24 h from 40 patients with advanced malignant disease
      who had received a known four-hourly oral dose of either diamorphine or morphine
      in an elixir or of diamorphine by injection for at least 3 days. 2 Samples were
      assayed for total urinary morphine (free and conjugated) by gas-liquid
      chromatography. 3 The percentage of the administered dose recovered as morphine
      was: (a) diamorphine hydrochloride by injection: 70% (s.d. 25) (b) diamorphine
      hydrochloride by mouth: 77% (s.d. 27) (c) morphine sulphate by mouth: 56% (s.d.
      21) 4 It is suggested that diamorphine hydrochloride is completely absorbed by
      the gastro-intestinal tract but that morphine sulphate is only some two-thirds
      absorbed.

PMID- 22454936
TI  - Bioavailability of different preparations of paracetamol.
AB  - 1 Plasma drug concentrations in eight volunteer subjects following oral
      administration of six preparations of paracetamol have been studied. 2
      Significant interindividual differences in plasma paracetamol concentration were
      found within 1 h but there were no consistent differences between the different
      drug preparations. The results indicate that all the preparations have equivalent
      bioavailability. 3 In four subjects, tested with the same preparation on two
      occasions, the findings suggest that drug absorption may differ from one occasion
      to another.

PMID- 22454937
TI  - alpha-adrenoceptor blocking drugs, pressor responses to noradrenaline, and the
      ankle jerk in man.
AB  - 1 Changes in pressor responses to infused noradrenaline and in triceps surae jerk
      amplitude have been measured after the i.v. administration of: chlorpromazine,
      thioridazine, prochlorperazine, dimethothiazine, indoramin, benzoctamine and
      clonidine. 2 Each of the drugs blocked pressor responses to noradrenaline and
      reduced triceps surae jerk amplitude, but little correlation was found between
      their potencies in the two systems. 3 The effects of the drugs on the triceps
      surae jerk are not incompatible with an action at a spinal alpha-adrenoceptor
      site, but other pharmacological factors may be involved, such as penetration of
      the drugs into the central nervous system, and differences in their uptake(1)
      blocking activity.

PMID- 22454938
TI  - The effects of oral AH 5158, a combined alpha and beta-adrenoceptor antagonist,
      in healthy volunteers.
AB  - 1 In healthy male volunteers after single oral doses, AH 5158 produced inhibition
      of exercise induced tachycardia, falls in systolic and diastolic pressure at rest
      and in response to exercise, which are probably related to combined beta- and
      alpha-adrenoceptor antagonism. 2 At increasing doses from 100 mg to 400 mg there
      exists a dose related antagonistic effect, though the dominant effect of beta
      adrenoceptor antagonism is more easily demonstrable than is alpha antagonism. 3
      As indicated by the pattern of pharmacological effects, absorption of the oral
      drug is good and the duration of action of a 400 mg dose is approximately 8
      hours. 4 Despite being administered in beta-adrenoceptor blocking doses, AH 5158
      had no adverse effects upon peak expiratory flow at rest or in response to
      exercise. 5 It is concluded that the pharmacological profile of this combined
      alpha- and beta-adrenoceptor antagonism suggests a potential therapeutic role as
      an antihypertensive drug.

PMID- 22454939
TI  - Dose related effect of fenfluramine and norfenfluramine on glucose uptake into
      human isolated skeletal muscle.

PMID- 22454940
TI  - Attempted suicide with potassium clorazepate.

PMID- 22454941
TI  - The influence of urine pH on the renal excretion of ICI 66082 in man.

PMID- 22454942
TI  - A simple method for the estimation of theophylline in plasma by gas liquid
      chromatography.

PMID- 22454943
TI  - Interactions of amitriptyline with guanethidine and thymoxamine in the human
      iris.

PMID- 22454944
TI  - The clinical consequences of chronic hepatic enzyme induction by anticonvulsant
      drugs.

PMID- 22454945
TI  - Gastric emptying and drug absorption.

PMID- 22454946
TI  - The effects of drugs on erythrocytes in vitro: Heinz body formation, glutathione
      peroxidase inhibition and changes in mechanical fragility.
AB  - 1 The relationship between mechanical fragility, glutathione peroxidase
      inhibition and Heinz body formation, in erythrocytes exposed to oxidant drugs in
      vitro, has been investigated. All drugs tested caused Heinz body formation, and
      with the exception of acetyl salicylic acid and salicylic acid, also caused
      increased erythrocyte mechanical fragility. 2 There was a direct relationship
      between mechanical fragility and drug concentration. Mechanical fragility
      increased in parallel with Heinz body formation, with primaquine, gentisic acid,
      ascorbic acid and potassium chlorate. In contrast Heinz body formation occurred
      at drug concentrations which did not cause a marked increase in mechanical
      fragility in the case of menadione, acetyl phenylhydrazine and phenylhydrazine. 3
      The degree of inhibition of glutathione peroxidase was directly related to
      increased mechanical fragility with menadione, gentisic acid and potassium
      chlorate. However other substances causing increased mechanical fragility
      resulted in little or no loss of glutathione peroxidase activity. 4 The results
      show that there is no constant relationship between mechanical fragility caused
      by drugs, the formation of Heinz bodies and the inhibition of glutathione
      peroxidase. The factors contributing to oxidant drug-induced haemolysis appear to
      be variable and depend upon the drug concerned.

PMID- 22454947
TI  - Effect of the imidazoline-derivative ST-91 on heart rate and blood pressure in
      healthy man.
AB  - 1 ST-91, 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride produces in
      animal experiments bradycardia, and in larger doses, also hypertension, due to
      alpha-sympathomimetic activity and probable central sympathetic inhibition. 2 The
      effects of ST-91, after oral administration, were studied in 10 healthy
      volunteers. A dose-dependent, significant decrease of the heart rate was
      observed. On average the resting heart rate was reduced by 11-19 beats/min (15
      29%). During exercise the decrease of the heart rate was less pronounced. After
      the largest dose there was a fall of the systolic blood pressure during exercise
      averaging at 14-15 mmHg (11-12%). Otherwise the blood pressure remained
      unchanged. 3 Eight out of the 10 test-subjects complained of hair-raising and
      goose-flesh after all doses, due to the alpha-sympathomimetic effect of the drug.
      No toxic effects were observed.

PMID- 22454948
TI  - Effect of caffeine on sleep: EEG study in late middle age people.
AB  - 1 The effect of caffeine alkaloid base (300 mg) on whole night sleep was
      investigated by electrophysiological techniques in six late middle age subjects
      (mean age 56 years), comparison being made with decaffeinated coffee and with no
      drink prior to sleep, using each condition five times in a balanced order on non
      consecutive nights. 2 After caffeine the mean total sleep time decreased on
      average by 2 h, the mean sleep latency increased to 66 minutes. The number of
      awakenings increased and the mean total intervening wakefulness was more than
      doubled after caffeine. 3 In the first 3 h of sleep a decreased amount of stage 3
      + 4 was observed, accompanied by an increased amount of stage 2 and of
      intervening wakefulness, without a significant change in the amount of rapid eye
      movement sleep. 4 The change in sleep pattern observed suggests an increased
      capability for arousal and decreased ability to develop or sustain deeper stages
      of non-rapid eye movement sleep after caffeine.

PMID- 22454949
TI  - Human performance after a barbiturate (heptabarbitone).
AB  - 1 The residual effects of heptabarbitone given overnight were studied by an
      adaptive tracking technique. Decrements in performance were observed at the 10 h
      interval after 200 mg, at the 10 h and 13 h intervals after 300 mg and at the 10
      h, 13 h, 16 h and 19 h intervals after 400 mg of the drug. Decrements in
      performance at each interval and the persistence of the effects were dose
      related. 2 Subjective assessments of performance correlated with measured
      performance, but the subjects, as a group, over-estimated their performance after
      placebo and heptabarbitone. With heptabarbitone (400 mg) highly significant
      decrements in performance persisted to the 19 h interval after ingestion, but
      subjective assessments of performance to the 19 h interval did not differ
      significantly from subjective assessments of control activity of the day before.
      3 Individual blood concentrations of heptabarbitone did not give a significant
      correlation with individual performance decrements, though the blood
      concentrations and performance decrements at each dose were related.

PMID- 22454950
TI  - Preliminary assessment of RX 72601, a new anticholinesterase in man: reversal of
      competitive neuromuscular blockade.
AB  - 1 The effect of RX 72601, neostigmine plus atropine, or saline on neuromuscular
      blockade with (+)-tubocurarine was studied in a double blind trial in four
      healthy male volunteers. 2 The methods used to assess neuromuscular function were
      voluntary grip strength and indirectly evoked muscle twitches. The muscarinic
      action was assessed by measuring intestinal motility with a pressure sensitive
      radio pill, and auscultation of the abdomen. Blood pressure and pulse rate were
      also recorded. The degree of acetylcholinesterase inhibition achieved in whole
      blood was determined before and at intervals after the administration of the
      anticholinesterases. 3 Both RX 72601 (0.66-0.83 mg) and neostigmine (2.5 mg)
      completely reversed the neuromuscular blockade produced by tubocurarine, but the
      time course of reversal differed. RX 72601 (0.66-0.83 mg) produced similar
      inhibition of acetylcholinesterase in whole blood to neostigmine (2.5 mg). The
      doses of RX 72601 used caused minimal stimulation at muscarinic sites as
      evidenced by the limited effect on pulse rate and intestinal activity. 4 It was
      concluded that RX 72601 could be safely used to reverse the effects of
      neuromuscular blockade without the need for premedication with atropine.

PMID- 22454951
TI  - The effects of salbutamol and terbutaline on physiological tremor, bronchial tone
      and heart rate.
AB  - 1 The effects of oral doses of the bronchodilator drugs, salbutamol (4 and 8 mg)
      and terbutaline (5 and 10 mg), on physiological tremor, bronchial tone, heart
      rate and blood pressure were studied in six normal subjects. 2 Both drugs
      produced a significant increase in physiological tremor, compared with placebo.
      Terbutaline, but not salbutamol, produced a dose related response. No significant
      differences were observed between drugs. 3 Terbutaline (5 and 10 mg) and
      salbutamol (8 mg) produced a significant bronchodilatation compared with placebo.
      Dose related responses were obtained with both drugs, although this reached
      significance only with terbutaline. 4 Both doses of each drug produced a
      tachycardia, although this was only statistically significant with the high
      doses. 5 No significant change in blood pressure was observed with either drug. 6
      Peak effects of salbutamol occurred between 1 and 3 h and terbutaline between 1
      and 4 hours. Both drugs were still active at 6 hours.

PMID- 22454952
TI  - The influence of urinary pH on the elimination of mexiletine.
AB  - 1 The plasma elimination half-life of mexiletine was measured in four subjects
      when the urine was rendered (a) acidic and (b) alkaline. 2 Urinary acidification
      (pH 5.0) was associated with a plasma elimination half-life of 2.8 h and 57.5% of
      the intravenous dose was excreted in the urine within 48 hours. When the urine
      was alkaline (pH 8.0) the half-life increased to 8.6 h with negligible amounts of
      drug appearing in the urine. 3 Urinary pH varies widely in cardiac patients and
      should be controlled or monitored to provide better therapeutic precision with
      mexiletine.

PMID- 22454953
TI  - An assessment of gastric emptying by breathalyser.
AB  - 1 A breathalyser has been used to measure blood alcohol levels at short intervals
      to produce an absorption curve which we have shown is reproducible. 2 Changes in
      the rate of absorption which reflect changes in gastric emptying times produced
      by metoclopromide and propantheline have been demonstrated. 3 The breathalyser
      technique described appears to offer a simple method of studying the effects of
      drugs on the rate of gastric emptying.

PMID- 22454954
TI  - The effect of prednisone treatment on the half-life of intravenous
      hydrocortisone.
AB  - 1 The half-life of hydrocortisone (cortisol) has been measured in six patients
      before and after a three-week course of prednisone given for asthma. 2 There was
      considerable variation in peak plasma level of cortisol both within and between
      patients, but on both occasions the plasma half-lives were the same. 3 It was
      concluded that short courses of prednisone have no effect on the handling of
      hydrocortisone.

PMID- 22454955
TI  - The persistence of adriamycin in man and rat.
AB  - 1 Adriamycin was administered as a single intravenous dose. The plasma
      concentration in man and rat decayed as a double exponential function of time. 2
      A two compartment model was used to predict plasma and tissue concentrations in
      man and the rat. The validity of the tissue concentration predictions was
      confirmed experimentally in the rat. 3 Tissue components had a high capacity for
      the drug. There was evidence in the rat of preferential accumulation in the
      liver, spleen and bone marrow. 4 The large tissue capacity and the prolonged half
      time for elimination predispose to accumulation. This may be responsible for the
      greater toxicity of treatment schedules with short intervals between consecutive
      doses.

PMID- 22454956
TI  - Ethosuximide: liver enzyme induction and D-glucaric acid excretion.
AB  - 1 A study has been carried out to determine if ethosuximide induces liver
      enzymes. 2 Ethosuximide did not affect the urinary excretion of D-glucaric acid
      by healthy adult subjects nor was the mean daily D-glucaric acid excretion of
      three epileptic children on long term ethosuximide therapy different from that of
      three matched controls. 3 Ethosuximide (10 mg/kg or 50 mg/kg daily) did not
      influence D-glucaric acid excretion or liver microsomal protein and cytochrome
      P450 contents of guinea pigs but at a dose of 100 mg/kg daily in rats it
      increased liver microsomal protein and cytochrome P450 without altering D
      glucaric acid excretion. 4 These results suggest that at anticonvulsant doses
      ethosuximide is unlikely to induce liver enzymes. The precise relationship
      between D-glucaric acid excretion and liver enzyme induction remains in doubt.

PMID- 22454957
TI  - Urinary D-glucaric acid excretion and plasma antipyrine kinetics during enzyme
      induction.
AB  - 1 Changes in urinary D-glucaric acid excretion following a 14 day course of
      antipyrine to produce enzyme induction have been compared in normal volunteers
      with changes in plasma half lives and steady state levels of antipyrine. 2
      Urinary D-glucaric acid excretion for the group rose significantly with
      induction, while there was a significant fall in the mean plasma antipyrine half
      life and steady state levels. The extent of the increase in urinary D-glucaric
      acid excretion was inversely related to the pre-induction level, and this also
      applied to the change in antipyrine half lives. 3 Although in individuals,
      urinary D-glucaric acid excretion and plasma levels of antipyrine changed in
      parallel, there was no numerical correlation in the group as a whole between
      these two tests either before or after enzyme induction. 4 These findings are
      consistent with other recently reported evidence that plasma drug kinetics and
      other microsomal enzyme functions are not necessarily affected to the same degree
      by agents with enzyme inducing properties.

PMID- 22454958
TI  - The influence of diphenhydramine on the absorption of methaqualone in man.
AB  - 1 The effects of diphenhydramine on the buccal absorption, in vivo absorption and
      the in vitro dissolution of methaqualone have been studied. 2 Diphenhydramine
      significantly reduced the buccal absorption of methaqualone and the effect was
      dose and pH dependent. In vivo, diphenhydramine did not alter the rate of
      absorption or the distribution of methaqualone in blood. In vitro, the presence
      of diphenhydramine increased the rate of dissolution of methaqualone and the
      effect was more marked when the particle size was small. 3 The reasons for and
      the implications of these apparently contradictory results are discussed and it
      is concluded that any increased efficacy resulting from combining diphenhydramine
      with methaqualone cannot be due to increased plasma drug levels.

PMID- 22454959
TI  - Plasma concentrations of methimazole, a metabolite of carbimazole, in
      hyperthyroid patients.
AB  - 1 Carbimazole was administered to nine hyperthyroid patients, and blood samples
      were taken at various time intervals for analysis of carbimazole, and its
      metabolite methimazole.2 A technique was developed for the measurement of
      methimazole in serum using a High-Pressure Liquid Chromatograph, which could
      detect nanogram quantities of this metabolite.3 After a single oral dose, the
      patients' blood levels appeared to fall into two groups, either those with a
      maximum concentration of methimazole between 30 and 60 min, or those whose
      maximum was 2 to 3 hours.4 The results would suggest that there could be a
      correlation between the high level of methimazole in serum and the high thyroxine
      concentration found in some patients.

PMID- 22454960
TI  - Charcoal haemoperfusion for paracetamol overdose.
AB  - 1 A controlled trial of charcoal haemoperfusion as an early treatment for
      paracetamol overdose showed no benefit. 2 The plasma clearances of paracetamol by
      the charcoal column were variable and disappointingly small (range 4-119
      ml/minute). The cumulative amounts removed were also low, mean 1.4 g (range 0.2
      5.2 g). 3 No clinical problems were encountered with the technique of
      haemoperfusion and in particular the drop in blood platelet counts was small
      (mean fall 16%).

PMID- 22454961
TI  - The effect of fluphenazine decanoate (modecate) on hepatic microsomal enzyme
      activity in man.

PMID- 22454963
TI  - Divine of body: the remains of Egyptian kings-preservation, reverence, and memory
      in a world without relics.

PMID- 22454964
TI  - What remains? Anti-Communism, forensic archaeology, and the retelling of the
      national past in Lithuania and Romania.

PMID- 22454965
TI  - Demonic possession, literacy and "superstition" in early modern England.

PMID- 22454966
TI  - "Rejoicing in potatoes": the politics of consumption in England during the
      "hungry forties".

PMID- 22454967
TI  - Margaret Mead amongst the natives of Great Britain.

PMID- 22454968
TI  - The economic origins of cleanliness in the Dutch golden age.

PMID- 22454969
TI  - Necropoles and nationality: land rights, burial rites and the development of
      Tunisian national consciousness in the 1930s.

PMID- 22454970
TI  - Visual dangers and delights: nude photography in East Germany.

PMID- 22454971
TI  - Scurrilous jests and retaliatory abuse in Shakespeare's "Troilus and Cressida".
AB  - With its unexpected and relentless staging of verbal rather than physical
      violence, Shakespeare's Troilus and Cressida reveals a deep engagement with late
      Tudor conflicts over the appropriate uses of satiric discourse in the public
      field. In particular, the play reimagines the aggressive response of magistrates
      who seek to control and recast various species of abusive language, thereby
      politicizing the "sportive malice" enacted in the subplots of Shakespeare's late
      comedies. No-where is this official manipulation of satirical voices more
      insistent-and ultimately destabilizing-than in the libels devised by Ulysses. His
      repeated attempts to shame the retired warrior Achilles draw on recently popular
      early modern strategies of confessional escalation and abuse, which the
      Elizabethan bishops paradoxically promoted through their own polemical efforts to
      limit the fallout from the Martin Marprelate scandal of 1588-1589. Ultimately, as
      Ulysses extends the internecine strife initiated by Achilles' "scurril
      jests,"Troilus and Cressida comes to dispel the notion that such tactics can
      guarantee compliance with official policy. In the play's fragmentary final act,
      satire emerges as an especially corruptive source of dissension-the ancients'
      perverse legacy to an England deeply alarmed by yet fervently committed to verbal
      violence.

PMID- 22454972
TI  - Venus, Serena, and the inconspicuous consumption of blackness: a commentary on
      surveillance, race talk, and new racism(s).
AB  - As the U.S. population becomes more racially diverse and different groups move in
      to previously White-dominated spaces, new techniques of exclusion and
      marginalization are being employed in an effort to regulate the opportunities and
      progress available to racialized minority groups. In this article, the author
      argues that mass media's preoccupation with the Williams sisters' "on-court" play
      and "off-court" activities constitutes a form of surveillance that is used by
      Whites to identify, observe, and ultimately, limit the range of available
      representations of Venus and Serena Williams. The author also suggests that this
      kind of public scrutiny produces racialized images and narratives constitutive of
      "race talk," a key manifestation of the new racism(s) characteristic of the
      politics of this sociohistorical moment.

PMID- 22454973
TI  - Concurrent validity of the Learning and Study Strategies Inventory (LASSI): a
      study of African American precollege students.
AB  - Concurrent validation procedures were employed, using a sample of African
      American precollege students, to determine the extent to which scale scores
      obtained from the first edition of the Learning and Study Strategies Inventory
      (LASSI) were appropriate for diagnostic purposes. Data analysis revealed that 2
      of the 10 LASSI scales (i.e., Anxiety and Test Strategies) significantly
      correlated with a measure of academic ability. These results suggested that
      scores obtained from these LASSI scales may provide valid assessments of African
      American precollege students' academic aptitude. Implications for teachers,
      school counselors, and developmental studies professionals were discussed.

PMID- 22454976
TI  - [Health service research (16). Sequential data analysis, with reference to
      hierarchical models].

PMID- 22454974
TI  - Nationalism, racism and propaganda in early Weimar Germany: contradictions in the
      campaign against the "black horror on the Rhine".
AB  - During the early 1920s, an average of 25,000 colonial soldiers from North Africa,
      Senegal and Madagascar formed part of the French army of occupation in the
      Rhineland. The campaign against these troops, which used the racist epithet
      'black horror on the Rhine' (schwarze Schmach am Rhein), was one of the most
      important propaganda efforts of the Weimar period. In black horror propaganda,
      images of alleged sexual violence against Rhenish women and children by African
      French soldiers served as metaphors for Germany's 'victimization' through the
      Versailles Treaty. Because the campaign initially gained broad popular and
      official support, historians have tended to consider the black horror a
      successful nationalist movement bridging political divides and strengthening the
      German nation state. In contrast, this essay points to some of the contradictions
      within the campaign, which often crystallized around conflicts over the nature of
      effective propaganda. Extreme racist claims about the Rhineland's alleged
      'mulattoization' (Mulattisierung) increasingly alienated Rhinelanders and
      threatened to exacerbate traditional tensions between the predominantly Catholic
      Rhineland and the central state at a time when Germany's western borders seemed
      rather precarious in the light of recent territorial losses and separatist
      agitation. There was a growing concern that radical strands within the black
      horror movement were detrimental to the cohesion of the German nation state and
      to Germany's positive image abroad, and this was a major reason behind the
      campaign's decline after 1921/22. The conflicts within the campaign also point to
      some hitherto neglected affinities between the black horror and subsequent Nazi
      propaganda.

PMID- 22454977
TI  - Degradation of carbon tetrachloride in the presence of iron and sulphur
      containing compounds.
AB  - The effect of several sulphur compounds: sodium sulphate, sodium sulphide,
      ferrous sulphide,pyrite and an organosulphonic acid on the kinetics of the iron
      (Fe  degrees ) induced degradation of carbon tetrachloride was examined under
      aerobic conditions. It was observed that all of the sulphur compounds
      investigated significantly accelerated the reaction. The mechanisms of the
      processes studied as well as their possible influence on the efficiency of the
      iron-induced dehalogenation of pollutants, both in situ and in above-ground
      treatment are discussed.

PMID- 22454978
TI  - Influence of some groundwater and surface waters constituents on the degradation
      of 4-chlorophenol by the fenton reaction.
AB  - The Fenton reaction has been applied to the degradation of 4-chlorophenol in
      aqueous solutions containing various anions. The rate of the reaction was found
      to decrease in the following order of anions (at the same concentrations): CIO
      (4) ~ NO (3)- > SO(4) (2-) > CI(-)> >HPO(4) (2-) > HCO(3)(-). Degradation of the
      pollutant containing the above anions at concentrations typical of those found in
      groundwater and surface waters was affected in a similar way. The results are
      discussed in terms of the effects of these anions on the rates of the oxidation
      of ferrous anion as well as on their role in the scavenging of hydroxyl radical

PMID- 22454979
TI  - "No cure, no money", or the invisible hand of quackery: the language of commerce,
      credit, and cash in eighteenth-century British medical advertisements.

PMID- 22454981
TI  - [Genitourinary cancer, biomarker; current progress].

PMID- 22454980
TI  - "To sing the town": women, place, and print culture in eighteenth-century Bath.

PMID- 22454982
TI  - [Biomarker for molecular targeting therapy against renal cell carcinoma].

PMID- 22454983
TI  - [Prostate cancer].

PMID- 22454984
TI  - [Biomarker for bladder cancer].

PMID- 22454985
TI  - [Current topics for biomarker of testicular cancer].

PMID- 22454986
TI  - [Public health for scientific analysis of society and health (12). Preventive
      medicine].

PMID- 22454987
TI  - [Public health monitoring report (9). A need for health impact assessment and a
      proposal for guidance by the Japanese Society of Public Health].

PMID- 22454988
TI  - [Health services research (15). Application of econometric techniques to health
      service research--search of possibility for observational (non-experimental)
      data].

PMID- 22454989
TI  - [Public health for scientific study of society and health (11). Keypoints in
      ethical guidelines for medical research].

PMID- 22454991
TI  - [Public health monitoring report (8). Health effects of the temporary employment
      status].

PMID- 22454992
TI  - [Effects of root rot on saponin content in Panax notoginseng].
AB  - OBJECTIVE: To provide the proof for the quality evaluate and the utilization of
      root rot Panax notoginseng, the contents of saponins were analyzed, such as
      ginsenoside Rb1, ginsenoside Rg1 and notoginsenoside R1 in the rotted and normal
      roots. METHOD: The saponin contents were contrasted with samples in same field
      and different rotted degree Panax notoginseng. The single saponin was determined
      by HPLC and the total saponin was determined by macro resin absorbing
      colorimetric method. RESULT: The total saponin was decreased 30.88% in sick root
      than in normal root. The contents of three single saponin R1, Rg1, Rb1 were
      decreased 25.53%, 11.26% and 17.82%, respectively. CONCLUSION: The saponin
      contents was declined with the degree of rot. The rot had no effect on the
      proportion of the three single saponin.

PMID- 22454993
TI  - [Distribution of four alkaloids in plants of Berberis].
AB  - In order to assess a simple and effective method for sensitive detection of
      alkaloids in Berberis plants, HPLC with gradiation elution is described. This
      method was developed for determination of four kinds of alkaloids including
      berbamine, jatrorrhizine, berberine and palmatine in methanolic extracts from
      bark and core of root and stem of Berberis. The linear correlations of berberine,
      jatrorrhizine, berbamine and palmatine were in the range of 0.028 - 4.74 microg
      (r = 0.9998), 0.012 - 2.0 microg (r = 0.9996), 0.026 - 0.52 microg (r = 0.9999),
      0.015 - 2.56 microg (r = 0.9998), respectively. The content of alkaloids had
      obvious difference in Berberis plants from different habitats and different
      parts.

PMID- 22454994
TI  - [Microscopic quantitative study on Saiga tatarica in "lingyang qing fei pill"].
AB  - OBJECTIVE: To determine Saiga tatarica content in "Lingyang Qing Fei Pill".
      METHODS: Volumetric analysis combined with quantitative microscopy was used to
      determine Saiga tatarica content by sample itself as standard substance. RESULT
      AND CONCLUSION: The method of determining the content of Saiga tatarica is simple
      and creditable.

PMID- 22454995
TI  - [Study on HPLC fingerprint of Herba Veronicae Dilatatae].
AB  - OBJECTIVE: To establish HPLC fingerprint of Herba Veronicae Dilatatae. METHODS:
      Beckman C18 column was used,with mixtures of 0.5% ice acetic acid-methanol as
      mobile phase. The flow rate was 1 mL/min. The wavelength of detection was 254 nm.
      RESULTS: After the mutual mode of HPLC fingerprint was set up, comparsion of
      similar degree with the medicinal materials of different batch were carried out.
      CONCLUSION: According to the selected chromatographic conditions, a good
      fingerprint has been described. The method is simple, accurate and reproducible.
      It may have practical value for the quality control of samples of Herba Veronicae
      Dilatatae.

PMID- 22454996
TI  - [Effects of hops on ovariectomized obese rats].
AB  - OBJECTIVE: To investigate the effects of hops on obesity in ovariectomy rats.
      MEHTODS: After ablating bilateral ovarian, adult Sprague-Dawley rats were drinken
      water extracts of hops and its effects on body weight were observed. On the
      seventh weekend, blood was collected to assay serum free fat acid (FFA), total
      anti-oxidative capacity (T-AOC), malondialdehyde (MDA), estrogen, testosterone
      and insulin. RESULTS: Compared with SHAM group, rats in OVX group displayed the
      higher weight, serum FFA, MDA and levels of insulin, lower serum levels of
      estrogen and testosterone and T-AOC. After drinken water extracts of hops,
      compared with OVX group, rats in OVX + hops group had lower weight, serum FFA,
      MDA, levels of insulin and higher serum T-AOC. CONCLUSION: Hops could promote
      weight loss in OVX rats. Hops maybe have estrogen activity. It can increase
      sensibitity of insulin and elevate anti-oxidative capacity.

PMID- 22454997
TI  - [Study on the inhibitory effect of cepharanthine on herpes simplex type-1 virus
      (HSV-1) in vitro].
AB  - OBJECTIVE: To assay the inhibitory effects of cepharanthine on HSV-1 in vitro.
      METHODS: Vero cells were infected by HSV-1 and cultured with serial dilutions of
      cepharanthine. The inhibitory effects of cepharanthine were evaluated with
      cytopathogenic effects (CPE). RESULTS: The CPE of cells infected by HSV-1 were
      inhibited significantly, resulting in higher cell survival rates. CONCLUSION: The
      results showed that cepharanthine had obvious HSV-1 inhibitory efficacy.
      Therefore, it may become a potential candidate in drug development and deserves
      further research on animal experiment and antiviral mechanisms.

PMID- 22454998
TI  - [Studies on the antidiabetic effect of konjac glucomannan with different
      molecular chains on experimental diabetes mice].
AB  - The antidiabetic effect of konjac glucomannan with different molecular chains on
      experimental diabetes mice was studied. The result showed that KGM- I, KGM-II,
      KGM-III and konjac flour can lower blood sugar of alloxan-induced hyperglycemic
      mice. When the dose was 1.5 g/kg, the decrease rates of blood sugar was 55.37%,
      80.60%, 33.44% and 40.9%, respectively. It also showed that KGM-II (Po, 0.2 g/kg.
      d x 7d) can significantly intensify DTH induced by DNFB and improve phagocytosing
      function of peritoneal macrophage (PM phi) separetely.

PMID- 22454999
TI  - [The preliminary studies on antioxidation of three kinds of flavoniods from
      Litsea coreana].
AB  - In this paper, the antioxidation of three flavoniods from the leaves of Litsea
      coreana was tested by tissue homogenate MDA. The results showed that these
      compounds had the obvious effect of antioxidations with dose-effect relationship.
      And the activity is kaempferol > querctin-3-O-beta-D-glucopyranoside > kaempferol
      3-O-beta-D-glucopyranoside. Another, by comparison of the inhibitory rate of
      tissue homogenate MDA of heart, brain, liver and kidney, it was found that their
      effect is kidney > heart > liver > brain. This paper may provide some important
      scientific informations for the development and utilization of natural
      antioxidants--three flavoniods from the leaves of Litsea coreana.

PMID- 22455000
TI  - [Influence of yi nao capsule on epinephrine and norepinephrine during rat
      ischemia].
AB  - OBJECTIVE: To investigate the effect of home-made "Yi Nao Capsule" on epinephrine
      and norepinephrine levels in rat plasma during brain ischemia. METHODS:
      Experiments were performed on 180 - 220 g rat under chloral hydrate anesthesia.
      Brain ischemia was induced by bilateral common carotid ligation for 30 min. HPLC
      combined with electrochemical detection has been developed for the determination
      of epinephrine and norepinephrine in plasma samples. RESULTS: Epinephrine and
      norepinephrine concentration increased markedly (P<0.05) in brain ischemia rat.
      While the ischemia animal was fed on "Yi Nao capsule" priors to ischemia 30 min,
      norepinephrine and epinephrine conecentration decreased markedly (P<0.05).
      CONCLUSION: Ischemia induced by bilateral common carotid ligation leads to the
      increase of plasma epinephrine and norepinephrine and "Yi Nao capsule" can
      prevent this increase.

PMID- 22455001
TI  - [Comparison on dissolving sputum and anti-inflammation of "mao ju hong" and
      "guang ju hong"].
AB  - OBJECTIVE: To compare the role of dissolving sputum and anti-inflammation of "Mao
      Ju Hong" (MJH) and "Guang Ju Hong" (GJH). METHOD: Using phenolsulfonphthalein
      method and dimethyl benzene method, the roles of dissolving sputum and anti
      inflammation of MJH and GJH were studied. RESULT: The comparison between the same
      dosage MJH and GJH showed the result had significant dissimilarity, the role
      intensity of MJH was bigger than that of GJH. CONCLUSION: The quality of MJH is
      better than GJH at the angle of pharmacodynamics. It is coincident with the
      traditional opinion that the genuine material is good.

PMID- 22455002
TI  - [Experimental studies on anticoagulant activity of different extract of leech in
      vitro].
AB  - OBJECTIVE: To study the anticoagulant activity of different extracts of Leech.
      METHODS: Prothrombin time (PT), thrombin time (TT) and activated partial
      thromboplastin time (APTT) were determined by coagulometer for blood samples
      collected from abdominal vein of Wistar rat. RESULTS: PT, TT, APTT were prolonged
      remarkably by ethyl acetate part of Leech. PT was prolonged remarkably by hexane
      part and aqueous solution part of Leech. APTT was prolonged remarkably by n
      Butylalcohol part of Leech. CONCLUSION: The different extracts of Leech have
      obvious anticoagulant effects. There are new anticoagulant components different
      from hirudin in Leech.

PMID- 22455003
TI  - [Study on inhibitive effect of Limax extracts on Hela and study on the active
      component].
AB  - OBJECTIVE: To study the inhibitive effect of Limax extracts on Hela in culture.
      METHOD: In this study salting-out method is used to separate Limax extracts. The
      effect of Limax extracts is detected by microscope and MTT method. RESULTS: Limax
      extracts could inhibit the growth of Hela cell. The contents of the protein and
      the polysaccharides in Limax extracts were analyzed. CONCLUSION: The result
      showed the active component was not protein, may be polysaccharides.

PMID- 22455004
TI  - How important is the D in R&D?

PMID- 22455005
TI  - Clinical waste incinerators in Cameroon--a case study.
AB  - PURPOSE: Incinerators are widely used to treat clinical waste in Cameroon's
      Northwest Region. These incinerators cause public apprehension owing to purported
      risks to operators, communities and the environment. This article aims to
      summarize findings from an April 2008 case study. DESIGN/METHODOLOGY/APPROACH:
      Three incinerators were randomly selected and investigated for site, design and
      operating standards. Empirical field observation was adopted and data collected
      through inventory and informal interviews. Bottom ash samples collected from the
      incinerators were prepared according to standard procedures and analyzed for
      heavy metals using Inductively Coupled Plasma (ICP) Emission Spectroscopy.
      FINDINGS: Shortcomings associated with site selection, design and operation
      standards were identified. Chemical analysis revealed that Cr, Cu, Fe, Mn, Ni,
      Pb, Zn, Mg and Ca were present in the bottom ash with mean concentration ranging
      from 10 mg/kg for Pb to 178080 mg/kg for Ca. RESEARCH LIMITATIONS/IMPLICATIONS:
      For logistic reasons, feedstock quantity and quality into the incinerators were
      not investigated. Neither were soil samples around and away from the
      incinerators. PRACTICAL IMPLICATIONS: Although highly favored, clinical waste
      incineration methods in this region have to be reconsidered. A thorough health
      and environmental impact assessment is suggested before subsequent decisions on
      choice and disposal site is made. This will curb potential negative impacts to
      the environment and public health. ORIGINALITY/VALUE: This article adds a
      different perspective and sheds additional information to the debate on
      unsatisfactory clinical waste incinerators in resources-poor countries.
      Alternative methods to incineration are presented that will be helpful to
      practitioners.

PMID- 22455006
TI  - Factors relating to doctors' desire to change hospitals in Japan.
AB  - PURPOSE: This study seeks to investigate doctors' desire to change the hospital
      where they work to sustain higher quality care. DESIGN/METHODOLOGY/APPROACH: Self
      administered questionnaires were sent to doctors in Aichi Prefecture, Japan. Data
      were analyzed using univariate and logistic regression analysis and recursive
      partitioning. FINDINGS: Factors related to doctors' desire to change hospitals,
      according to logistic regression, were interaction between working hours and
      satisfaction with the hospital, evaluation, local government hospitals versus
      private ones, small vs large hospitals, ophthalmology versus internal medicine,
      desire to continue working as a hospital doctor and age. Additionally, working
      hours were also found to be related, based on recursive partitioning. RESEARCH
      LIMITATIONS/IMPLICATIONS: The response rate was low and sampling bias was
      observed--therefore results need careful interpretation. Also, because this was a
      cross-sectional study, causal relationships could not be identified. Desire to
      change hospitals, but not actual behavior, was measured. PRACTICAL IMPLICATIONS:
      Efforts to prevent doctors from changing hospitals should include considering job
      satisfaction and workload, doctor evaluation methods, support for career
      progression and organizational management. ORIGINALITY/VALUE: As the hospital
      doctor shortage in rural areas becomes more serious, exploring doctors' desire to
      leave their current hospital is meaningful for Japanese hospital managers and
      hospitals worldwide aiming to provide sustainable and higher quality care.

PMID- 22455007
TI  - Valproate in acute mania: is our practice evidence based?
AB  - PURPOSE: This audit was conducted on acute psychiatric in-patient wards with the
      aim of establishing if valproate prescribing in acute mania followed evidence
      based guidelines with particular emphasis on formulations used and whether
      accelerated valproate dosing was employed. DESIGN/METHODOLOGY/APPROACH: Case
      notes from 43 (42 percent male) patients admitted with mania and subsequently
      discharged on valproate were reviewed. Valproate formulation, weight measurement
      (necessary for dose-calculation in accelerated dosing), initial valproate dose
      and increments, serum valproate monitoring and other prescribed psychotropic
      agents were noted. FINDINGS: Most (95 percent) patients received sodium valproate
      (epilim chrono/generic), the remaining received valproate semi-sodium (depakote).
      All but one patient received antipsychotic medication in combination. Weight was
      recorded in only four (9 percent) patients. The mean valproate daily dose after
      the first week was 1,027mg (sd = 408). It took 29 (sd = 42) days to reach the
      maximum daily dose (1,426 mg sd = 467) from valproate initiation. Serum levels
      were monitored in 34 (79 percent) cases, but the mean period between valproate
      initiation to the first serum level test was 38 (sd = 47) days. A significant
      positive correlation was found between days taken to reach maximum dose and
      hospital stay (Spearman's rho = 0.41, n = 43, p = 0.006, two-tailed). PRACTICAL
      IMPLICATIONS: Accelerated valproate dosing was not common practice, which may
      have resulted in suboptimal efficacy, probably leading to combination treatment.
      ORIGINALITY/VALUE: This study highlights the need for adequate initial dosing and
      dose increments when treating manic patients and suggests current practice is not
      evidence-based. Local prescribing policy and national guidelines' influence on
      practice are discussed.

PMID- 22455008
TI  - A quality control application in healthcare management using experimental design
      criteria.
AB  - PURPOSE: The purpose of this paper is to determine the significant factors that
      cause delays in surgery operations in a hospital and factors that affect
      productivity of surgery clinics. DESIGN/METHODOLOGY/APPROACH: Data are collected
      from surgery clinics of an international hospital to identify main factors that
      affect delays in surgery operation. A design of experiment is then performed and
      the significance of the effects of these factors is determined. A regression
      model was also developed to find a relation between surgery delays and the
      selected factors. FINDINGS: The results show that such factors as the type of
      doctors and missing information significantly affect the delay in surgery
      operations as compared with some other factors, such as admission time considered
      in the study. RESEARCH LIMITATIONS/IMPLICATIONS: The models developed and the
      results obtained in this paper are specific to the application presented.
      However, the procedures are general and can be applied to similar problems.
      PRACTICAL IMPLICATIONS: The results of the study can be used to control important
      factors to reduce the delays in surgery operations, reduce risks in patient
      health related to these delays, reduce hospital costs and improve the
      productivity of these clinics. ORIGINALITY/VALUE: The paper considers a
      management problem related to surgery delays which has not been considered before
      and presents a procedure to study the causes of the problem. It provides a
      methodology that could be used to study similar problems in health care
      management systems and to improve these systems by analyzing operations and
      activities with respect to the factors that affect productivity and efficiency of
      such operations.

PMID- 22455009
TI  - Oral cancer prevention and early detection: knowledge and practice among Saudi
      Arabian healthcare practitioners.
AB  - PURPOSE: Despite the crucial role that healthcare practitioners (HCPs) have in
      preventing and detecting oral cancer (OC), studies suggest that dentists and
      physicians do not adequately detect early stage OC which is attributed to their
      attitude and knowledge. This Saudi Arabian study aims to assess HCP's knowledge
      and practice vis-a-vis OC's risk factors and patient evaluation.
      DESIGN/METHODOLOGY/APPROACH: A questionnaire was distributed to HCPs in six
      different Saudi Arabian settings. A total of 16 items representing a mixture of
      OC's risk and non-risk factors were measured. FINDINGS: The study found that only
      20.9 percent of HCPs could distinguish 11 items or more correctly. Additionally,
      when HCPs obtained the patient's medical history, no more than 32.3 percent
      routinely assessed ten important OC issues. Almost 36 percent of HCPs thought
      that attending to too many patients prevented them from taking proper medical
      histories, and 37.6 percent admitted that more training in preventing and
      detecting OC is needed. RESEARCH LIMITATIONS/IMPLICATIONS: Since there is no
      effective automated system to reach Saudi Arabian practitioners, the number of
      practitioners involved in this study is limited. PRACTICAL IMPLICATIONS: The
      knowledge and practice of HCPs with relation to OC do not appear to be sufficient
      and HCPs should have better and more training in OC prevention and early
      detection. ORIGINALITY/VALUE: It appears that Saudi Arabian HCPs do not
      adequately participate in OC's prevention and early detection. It is suggested
      that continuous education strategies in Saudi Arabia should be reassessed and
      emphasis given to OC diagnosis.

PMID- 22455010
TI  - The two-week rule for suspected colorectal cancer: patient experience and
      psychological impact.
AB  - PURPOSE: There has been considerable interest in the "two-week rule" referral
      pathway efficacy for patients with suspected colorectal cancer. This study aims
      to explore the psychological impact on these patients.
      DESIGN/METHODOLOGY/APPROACH: Consecutive patients referred for urgent
      investigations under the "two-week rule" were invited to take part in semi
      structured interviews using interpretative phenomenological analysis (IPA).
      Interviews were audio-taped, transcribed verbatim and analysed using investigator
      triangulation to enhance data trustworthiness. FINDINGS: Ten out of 23 (43.5 per
      cent) patients consented to interviews; none were diagnosed with cancer. Four
      super-ordinate themes were explored, referring to the "making sense of the threat
      to health", impact on self, impact on others, reflections on the "two-week rule"
      referral, and its investigative process. Participants reported their anxiety,
      fear, vulnerability and coping mechanisms, but also raised concerns about the
      communication received during the "two-week rule" referral process. Female
      participants preferred a female endoscopist. ORIGINALITY/VALUE: This study is the
      first of its kind exploring the psychological effects of the "two-week rule"
      process for colorectal cancer, highlighting potential areas for improvement in
      patient information, and satisfaction with the referral process.

PMID- 22455011
TI  - Ionic liquids: past, present and future.
AB  - An overview of the field of low-melting ionic liquids is given from its inception
      in 1886 through to the present time. The subject is divided into an introductory
      section that summarizes the early history of the field, and differentiates its
      subsections, before addressing matters judged of some interest in "pre-surge" and
      "post-surge" stages of its development, focusing on physicochemical as opposed to
      the prolific synthetic and industrial aspects in which the author has no
      competence. We give a final section specifically to protic ionic liquids, which
      we consider to have particular scientific potential.

PMID- 22455012
TI  - Simulations of the structure and dynamics of nanoparticle-based ionic liquids.
AB  - We use molecular dynamics simulations over microsecond time scales to study the
      structure and dynamics of coarse-grained models for nanoparticle-based ionic
      liquids. The systems of interest consist of particles with charged surface groups
      and linear or three-arm counterions, which also act as the solvent. A comparable
      uncharged model of nanoparticles with tethered chains is also studied. The pair
      correlation functions display a rich structure resulting from the packing of
      cores and chains, as well as electrostatic effects. Even though electrostatic
      interactions between oppositely charged ions at contact are much greater than the
      thermal energy, we find that chain dynamics at intermediate time scales are
      dominated by chain hopping between core particles. The uncharged core particles
      with tethered chains diffuse faster than the ionic core particles.

PMID- 22455013
TI  - Using ethane and butane as probes to the molecular structure of 1-alkyl-3
      methylimidazolium bis[(trifluoromethyl)sulfonyl] imide ionic liquids.
AB  - In this work, we have studied the solubility and the thermodynamic properties of
      solvation, between 298 and 343 K and at pressures close to atmospheric, of ethane
      and n-butane in several ionic liquids based on the bis[(trifluoromethyl)
      sulfonyl]imide anion and on 1-alkyl-3-methylimidazolium cations, [CnC1Im] [NTf2],
      with alkyl side-chains varying from two to ten carbon atoms. The solubility of
      butane is circa one order of magnitude larger than that of ethane with mole
      fractions as high as 0.15 in [C10C1Im][NTf2] at 300 K. The solubilities of both n
      butane and ethane gases are higher for ionic liquids with longer alkyl chains.
      The behaviour encountered is explained by the preferential solvation of the gases
      in the non-polar domains of the solvents, the larger solubility of n-butane being
      attributed to the dispersive contributions to the interaction energy. The rise in
      solubility with increasing size of the alkyl-side chain is explained by a more
      favourable entropy of solvation in the ionic liquids with larger cations. These
      conclusions are corroborated by molecular dynamics simulation studies.

PMID- 22455014
TI  - Critical behaviour and vapour-liquid coexistence of 1-alkyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)amide ionic liquids via Monte Carlo simulations.
AB  - Atomistic Monte Carlo simulations are used to compute vapour-liquid coexistence
      properties of a homologous series of [C(n)mim][NTf2] ionic liquids, with n = 1,
      2, 4, 6. Estimates of the critical temperatures range from 1190 K to 1257 K, with
      longer cation alkyl chains serving to lower the critical temperature. Other
      quantities such as critical density, critical pressure, normal boiling point, and
      accentric factor are determined from the simulations. Vapour pressure curves and
      the temperature dependence of the enthalpy of vapourisation are computed and
      found to have a weak dependence on the length of the cation alkyl chain. The ions
      in the vapour phase are predominately in single ion pairs, although a significant
      number of ions are found in neutral clusters of larger sizes as temperature is
      increased. It is found that previous estimates of the critical point obtained
      from extrapolating experimental surface tension data agree reasonably well with
      the predictions obtained here, but group contribution methods and primitive
      models of ionic liquids do not capture many of the trends observed in the present
      study

PMID- 22455015
TI  - Phase behaviour, transport properties, and interactions in Li-salt doped ionic
      liquids.
AB  - We report on the influence of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)
      doping on the glass transition temperature (Tg), the ionic conductivity, and Li
      ion coordination of two dicationic ionic liquids (DILs) based on the TFSI anion.
      The results are compared to the behaviour of traditional mono-cationic ionic
      liquids. The cations of the DILs contain two imidazolium rings, connected by a
      decane hydrocarbon chain. Homogeneous mixtures of these ILs and LiTFSI can be
      obtained in a large concentration range. With increasing Li-salt concentration
      the ionic conductivity decreases whereas the glass transition temperature
      increases in both systems. However, the influence of the salt doping on the ionic
      conductivity and the glass transition temperature is low compared to typical mono
      cationic ionic liquids, based on for example the pyrrolidinium cation and the
      TFSI anion. This behaviour is mirrored in the average coordination number of TFSI
      anions around Li-ions, determined by Raman spectroscopy. The coordination number
      is systematically lower in the DILs, suggesting a connection between the
      difference in the Li-ion environment and the behaviour of the glass transition
      and the ionic conductivity. A Tg-scaled Arrhenius plot of the ionic conductivity
      shows that the ionic conductivity for all LiTFSI concentrations has the same
      temperature dependence, i.e., the fragility of the liquid is the same. This
      implies that the conduction process is dominated by the viscous properties of the
      liquids over the entire concentration range. This provides further support for
      linking the local environment of the Li-ions to the glass transition and
      conduction process in the ionic liquid/salt mixtures.

PMID- 22455016
TI  - New experimental evidence supporting the mesoscopic segregation model in room
      temperature ionic liquids.
AB  - The existence of a high degree of order over the mesoscopic spatial scale in room
      temperature ionic liquids is one of their most intriguing properties. Recently
      the possibility that such a feature, that is witnessed by the occurrence of
      peculiar low Q diffraction features, reflects nm-scale structural organization
      has been questioned on the basis of both experimental and computational studies.
      In this contribution we discuss these studies and present novel experimental
      evidence that confirm the existence of nm-scale spatial heterogeneities due to
      the segregation of apolar moieties dispersed in a polar network. The consequence
      of this scenario is that when the chain polarity gets closer to that of the
      charged head, the structural heterogeneities are no longer observed.

PMID- 22455017
TI  - Ionic liquids studied across different scales: a computational perspective.
AB  - For theoreticians, ionic liquids represent a major challenge. This is due to the
      fact that intermolecular interactions are particularly strong because of ionic
      liquids' ionicity. This, in turn, causes a subtle interplay between different
      scales which is encoded in the measured macro- and mesoscopic properties and also
      in the molecular electrostatic characteristics. Therefore, force fields have to
      describe the microscopic processes correctly in order to reproduce macroscopic
      properties accurately over a large range of state variables. Herein, imidazolium
      based ionic liquids were studied at different scales, going from the detailed
      quantum electronic scale to the classical atomistic scale. It is indicated how
      the information gained at each level could be used for the other scales. In
      particular, the issue of deriving suitable partial charges for use in classical
      force fields is addressed. The Blochl method was employed to generate partial
      charges reproducing the multipole distribution accurately for bulk systems. This
      led naturally to absolute ionic charges of less than /l e/, i.e., charge scaling.
      So, the monopole structure of the herein introduced force field mimics the
      quantum chemical behaviour observed in the liquid phase. This led to a
      substantial improvement in the description of dynamical properties of immediate
      experimental interest, such as electric conductivity. For further insight, the
      electric dipole moment of the ions was taken as physical indicator of their
      electronic structure. The electric dipole moment was found to fluctuate strongly
      and to depend on polarisation. Hence, our scale-combined study offers a gateway
      to rational design of models, based on the relevant underlying physics rather
      than on mere numerical parameterisation, and thereby to (possibly) more direct
      physical interpretation of experimental results.

PMID- 22455018
TI  - Temperature-dependent structure of ionic liquids: X-ray scattering and
      simulations.
AB  - In this article we determine the temperature-dependent structure of the
      tetradecyltrihexylphosphonium bis(trifluoromethylsulfonyl)amide ionic liquid
      using a combination of X-ray scattering and molecular dynamics simulations. As in
      many other room-temperature ionic liquids three characteristic intermolecular
      peaks can be detected in the structure function S(q). A prepeak or first sharp
      diffraction peak is observed at about q = 0.42 A(-1). Long range anion-anion
      correlations are the most important contributors to this peak. In all systems we
      have studied to date, this prepeak is a signature of solvation asymmetry. The
      peak in S(q) near q = 0.75 A(-1) is the signature of ionic alternation and arises
      from the charge ordered separation of ions of the same charge. The most intense
      diffraction peak near q = 1.37 A(-1) arises from short-range separation between
      ions of opposite charge combined with a significant contribution from cationic
      carbon-carbon interactions, indicating that cationic hydrophobic tails have
      significant contacts.

PMID- 22455019
TI  - Structure and dynamics in protic ionic liquids: a combined optical Kerr-effect
      and dielectric relaxation spectroscopy study.
AB  - The structure and dynamics of ionic liquids (ILs) are unusual due to the strong
      interactions between the ions and counter ions. These microscopic properties
      determine the bulk transport properties critical to applications of ILs such as
      advanced fuel cells. The terahertz dynamics and slower relaxations of simple
      alkylammonium nitrate protic ionic liquids (PILs) are here studied using
      femtosecond optical Kerr-effect spectroscopy, dielectric relaxation spectroscopy,
      and terahertz time-domain spectroscopy. The observed dynamics give insight into
      more general liquid behaviour while comparison with glass-forming liquids reveals
      an underlying power-law decay and relaxation rates suggest supramolecular
      structure and nanoscale segregation.

PMID- 22455020
TI  - 2D or not 2D: structural and charge ordering at the solid-liquid interface of the
      1-(2-hydroxyethyl)-3-methylimidazolium tetrafluoroborate ionic liquid.
AB  - Molecular dynamics simulations of a 5 nm-thick layer of the ionic liquid 1-(2
      hydroxyethyl)-3-methylimidazolium tetrafluoroborate, [(OH)C2C1im][BF4], over
      silica, alumina and boro-silicate glass substrates have been performed. The
      structure of the ionic liquid at the solid-liquid interface has been interpreted
      taking into account the corresponding normal density profiles, lateral
      interfacial structure, orientational ordering and planar density contours.
      Comparisons with experimental data suggest that the adsorption and stratification
      process of ionic liquids over solid substrates can be correctly modeled using a
      realistic rendition of a non-uniform amorphous substrate such as a glass
      material.

PMID- 22455021
TI  - From molten salts to room temperature ionic liquids: simulation studies on
      chloroaluminate systems.
AB  - An interaction potential including chloride anion polarization effects,
      constructed from first-principles calculations, is used to examine the structure
      and transport properties of a series of chloroaluminate melts. A particular
      emphasis was given to the study of the equimolar mixture of aluminium chloride
      with 1-ethyl-3-methylimidazolium chloride, which forms a room temperature ionic
      liquid EMI+ -AlCl4-. The structure yielded by the classical simulations performed
      within the framework of the polarizable ion model is compared to the results
      obtained from entirely electronic structure-based simulations: An excellent
      agreement between the two flavors of molecular dynamics is observed. When
      changing the organic cation EMI+ by an inorganic cation with a smaller ionic
      radius (Li+, Na+, K+), the chloroaluminate speciation becomes more complex, with
      the formation of Al2Cl7-, in small amounts. The calculated transport properties
      (diffusion coefficients, electrical conductivity and viscosity) of EMI+ -AlCl4-
      are in good agreement with experimental data.

PMID- 22455022
TI  - The interface ionic liquid(s)/electrode(s): in situ STM and AFM measurements.
AB  - The structure of the interfacial layer(s) between the extremely pure air- and
      water-stable ionic liquid 1-butyl-1-methylpyrrolidinium tris(pentafluoroethyl)
      trifluorophosphate and Au(111) has been investigated using in situ scanning
      tunneling microscopy (STM) at electrode potentials more positive than the open
      circuit potential. The in situ STM measurements show that layers/islands form
      with increasing electrode potential. According to recently published atomic force
      microscopy (AFM) data the anion is adsorbed even at low anodic overvoltages and
      adsorption becomes slightly stronger with increasing electrode potential.
      Furthermore, the number of interfacial layers increases with increasing electrode
      potential. The present discussion paper shows that these layers are not uniform
      and have a structure on the nanoscale, supporting earlier results that the
      interface electrode/ionic liquid is highly complex. It is also shown that the
      addition of solutes changes this structure considerably. AFM results reveal that
      in the pure liquid, interfacial layers lead to a repulsive force but the addition
      of 10 wt% of LiCl leads to an attractive force close to the surface. These
      preliminary results show that solutes strongly alter the interfacial structure of
      the ionic liquid/ electrode interface.

PMID- 22455023
TI  - Molecular-scale insights into the mechanisms of ionic liquids interactions with
      carbon nanotubes.
AB  - By means of fully atomistic molecular simulations we study basic mechanisms of
      carbon nanotube interactions with several different room temperature ionic
      liquids (RTILs) in their mixtures with acetonitrile. To understand the effects of
      the cation molecular geometry on the properties of the interface structure in the
      RTIL systems, we investigate a set of three RTILs with the same TFSI (bis
      (trifluoromethylsulfonyl)imide) anion but with different cations, namely, EMIm (1
      ethyl-3-methylimidazolium), BMIm (1-butyl-3-methylimidazolium) and OMIm (1-octyl
      3-methylimidazolium) ions. The cations have identical charged methylimidazolium
      'heads' but different nonpolar alkyl 'tails' where the length of the tail
      increases from EMIm to OMIm. The analysis of the simulation data results in the
      following conclusions: There is an enrichment of all molecular components of
      ionic liquids under study at the CNT surface with formation of several distinct
      layers even at the non-charged CNT surface. Mixing RTIL with acetonitrile
      decreases ion-counterion correlations in the electric double layer. Increase of
      the length of the non-polar 'tail' of cations increases the propensity of
      imidazolium-based cations to lay parallel to the CNT surface. At the CNT cathode
      TFSI anions and molecular cations are preferentially oriented parallel to the
      surface. At the CNT anode the TFSI anions are oriented parallel to the surface,
      however the preferred orientations of cations depend on the length of non-polar
      tail: EMIm cations are oriented perpendicular to the surface, BMIm cations can be
      in both parallel as well as perpendicular orientations, OMIm cations are oriented
      parallel to the surface. As a result, by applying an electric potential on the
      CNT electrode and/or varying the structure of molecular ions it is possible to
      change molecular ion orientations at the surface and, consequently, the structure
      of the electrical double layer at the CNT-RTIL interface.

PMID- 22455024
TI  - Graphene-based supercapacitors in the parallel-plate electrode configuration:
      ionic liquids versus organic electrolytes.
AB  - Supercapacitors with two single-sheet graphene electrodes in the parallel plate
      geometry are studied via molecular dynamics (MD) computer simulations. Pure 1
      ethyl-3-methylimidazolium tetrafluoroborate (EMI+BF4-) and a 1.1 M solution of
      EMI+BF4- in acetonitrile are considered as prototypes of room-temperature ionic
      liquids (RTILs) and organic electrolytes. Electrolyte structure, charge density
      and associated electric potential are investigated by varying the charges and
      separation of the two electrodes. Multiple charge layers formed in the
      electrolytes in the vicinity of the electrodes are found to screen the electrode
      surface charge almost completely. As a result, the supercapacitors show nearly an
      ideal electric double layer behavior, i.e., the electric potential exhibits
      essentially a plateau behavior in the entire electrolyte region except for sharp
      changes in screening zones very close to the electrodes. Due to its small size
      and large charge separation, BF4- is considerably more efficient in shielding
      electrode charges than EMI+. In the case of the acetonitrile solution,
      acetonitrile also plays an important role by aligning its dipoles near the
      electrodes; however, the overall screening mainly arises from ions. Because of
      the disparity of shielding efficiency between cations and anions, the capacitance
      of the positively-charged anode is significantly larger than that of the
      negatively-charged cathode. Therefore, the total cell capacitance in the parallel
      plate configuration is primarily governed by the cathode. Ion conductivity
      obtained via the Green-Kubo (GK) method is found to be largely independent of the
      electrode surface charge. Interestingly, EMI+BF4- shows higher GK ion
      conductivity than the 1.1 M acetonitrile solution between two parallel plate
      electrodes.

PMID- 22455025
TI  - Adsorption, absorption and desorption of gases at liquid surfaces: water on
      [C8C1Im][BF4] and [C2C1Iml][Tf2N].
AB  - The adsorption, absorption and desorption of water vapour at the liquid, and
      frozen solid, surfaces of two ionic liquids (ILs) is described. Surface kinetics
      were measured by sticking probability (S), and temperature programmed desorption,
      using line of sight mass spectrometry in ultra-high vacuum. The two ILs used were
      1-octyl-3-methylimidazolium tetrafluoroborate ([C8C1Im][BF4]) and 1-ethyl-3
      methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, (C2C1Im] [Tf2N]. At room
      temperature, continuous absorption into the bulk occurred (S approximately =
      0.12), which reduced with decreasing temperature, reaching zero when the ILs
      froze to glassy solids. At still lower temperatures, monolayer, and then
      multilayer, growth of water ice occurred at the solid surfaces. Adsorption is
      thought to occur first into a physisorbed state, and then into an ionic
      underlayer, the activation energy between the physisorbed state and the
      underlayer state being 48.0 +/- 0.8 kJ mol(-1) and 58 +/- 2.0 kJ mol(-1) for
      [C2C1Im][Tf2N] and [C8C1Im][BF4], respectively. From the underlayer state, water
      diffuses into the bulk rather than desorbing back into the gas phase. Adsorption
      and desorption kinetics were consistent with the existence of an outermost,
      hydrophobic layer covering the ionic underlayer. For [C8C1Im][BF4] this consists
      of outwardly orientated octyl chains, while for [C2C1Im][Tf2N] it is probably
      outward orientated ethyl and CF3 groups. Adsorption on the hydrophobic glassy
      surface was unusual, with S increasing for increasing coverage. The barrier to
      surface diffusion of water on the glassy surface of [C8C1Im][BF4] was 13 +/- 12
      kJ mol(-1).

PMID- 22455026
TI  - Nonlinear vibrational spectroscopic studies on waterlionic liquid([C(n)mim]TFSA:
      n = 4, 8) interfaces.
AB  - The interfaces of water/room temperature ionic liquids (RTIL) (1-alkyl-3-methyl
      imidazolium bis(trifluoromethylsulfonyl)amide ([C(n)mim]TFSA): n = 4, 8) are
      investigated by infrared-visible sum frequency generation (IV-SFG) vibrational
      spectroscopy and molecular dynamics (MD) simulation. SFG spectra taken within the
      SO stretch region drastically differ between air/RTIL and water/RTIL interfaces.
      When a RTIL surface is in contact with water, a broadened and blue-shifted SO2-ss
      mode peak is observed in the SFG spectra, indicating an inhomogeneous
      intermolecular interaction due to hydrogen bonding of the [TFSA]- anions and
      water molecules at the water/[C(n)mim]TFSA interface. MD simulations show the SO2
      groups of the anion are preferentially orientated toward the water phase, which
      is consistent with the SFG spectral features. Polar orientation of the [TFSA]
      anion originates from the ordered structure of the alkyl chains of [C(n)mim]+
      cations.

PMID- 22455027
TI  - Slow and fast capacitive process taking place at the ionic liquid/electrode
      interface.
AB  - Electrochemical impedance spectroscopy was used to characterise the interface
      between the ultrapure room temperature ionic liquid 1-butyl-1-methylpyrrolidinium
      tris(pentafluoroethyl)trifluorophosphate and a Au(111) working electrode at
      electrode potentials more positive than the open circuit potential (-0.14 V vs.
      Pt pseudo-reference). Plots of the potential-dependent data in the complex
      capacitance plane reveal the existence of a fast and a slow capacitive process.
      In order to derive the contribution of both processes to the overall capacitance,
      the complex capacitance data were fitted using an empirical Cole-Cole equation.
      The differential capacitance of the fast process is almost constant between -0.14
      V and +0.2 V (vs. Pt pseudo-reference) and decreases at more positive potentials,
      while the differential capacitance of the slower process exhibits a maximum at
      +0.2 V. This maximum leads to a maximum in the overall differential capacitance.
      We attribute the slow process to charge redistributions in the innermost ion
      layer, which require an activation energy in excess of that for ion transport in
      the room temperature ionic liquid. The differential capacitance maximum of the
      slow process at +0.2 V is most likely caused by reorientations of the 1-butyl-1l
      methylpyrrolidinium cations in the innermost layer with the positively charged
      ring moving away from the Au(111) surface and leaving behind voids which are then
      occupied by anions. In a recent Monte Carlo simulation by Federov, Georgi and
      Kornyshev (Electrochem. Commun. 2010, 12, 296), such a process was identified as
      the origin of a differential capacitance maximum in the anodic regime. Our
      results suggest that the time scales of capacitive processes at the ionic
      liquid/metal interface are an important piece of information and should be
      considered in more detail in future experimental and theoretical studies.

PMID- 22455028
TI  - Protic pharmaceutical ionic liquids and solids: aspects of protonics.
AB  - A series of new protic compounds based on active pharmaceutical ingredients have
      been synthesised and characterised. Some of the salts synthesised produced ionic
      liquids, while others that were associated with rigid molecular structures tended
      to produce high melting points. The "protonic" behaviour of these compounds was
      found to be a major determinant of their properties. Indicator studies, FTIR-ATR
      and transport properties (Walden plot) were used to probe the extent of proton
      transfer and ion association in these ionic liquids. While proton transfer was
      shown to have taken place in all cases, the Walden plot indicated strong ion
      association in the primary amine based examples due to hydrogen bonding. This was
      further explored via crystal structures of related compounds, which showed that
      extended hydrogen bonded clusters tend to form in these salts. These clusters may
      dictate membrane transport properties of these compounds in vivo.

PMID- 22455029
TI  - Electron solvation dynamics and reactivity in ionic liquids observed by
      picosecond radiolysis techniques.
AB  - On time scales of a nanosecond or less, radiolytically-generated excess electrons
      in ionic liquids undergo solvation processes and reactions that determine all
      subsequent chemistry and the accumulation of radiolytic damage. Using picosecond
      pulse radiolysis detection methods, we observed and quantified the solvation
      response of the electron in 1-methyl-1-butyl-pyrrolidinium bis
      (trifluoromethylsulfonyl)amide and used it to understand electron scavenging by a
      typical solute, duroquinone.

PMID- 22455030
TI  - Investigating the origin of entropy-derived rate accelerations in ionic liquids.
AB  - The effects on the rate and activation parameters of a series of Menschutkin
      processes on changing from a molecular solvent to an ionic liquid were
      investigated. The removal of delocalised pi-systems from the reagents does not
      affect the change in activation parameters on changing solvent. In each of the
      cases investigated, rate accelerations observed on moving to the ionic liquid
      could be attributed to an increase in reaction entropy. This suggests a specific
      interaction of the ionic liquid with the nucleophilic centre, rather than the
      delocalised pi-systems of either the electrophile or the nucleophile.

PMID- 22455031
TI  - Ab initio simulations of thermal decomposition and of electron transfer reactions
      in room temperature ionic liquids.
AB  - Selected aspects of the ab initio modelling of room temperature ionic liquids are
      discussed in our contribution, focusing on thermal decomposition reactions, and
      on the determination of the electrochemical stability window of these compounds.
      In both cases, we emphasise the role of ab initio simulation methods, able to
      deal simultaneously with the ionic and electronic side of the systems and
      phenomena under investigation.

PMID- 22455032
TI  - The ion speciation of ionic liquids in molecular solvents of low and medium
      polarity.
AB  - The ion speciation of ionic liquids dissolved in molecular liquids of low and
      medium polarity is studied experimentally and theoretically. The ion speciation
      in some representative systems is characterized by dielectric relaxation
      spectroscopy and electrical conductance measurements. A corresponding-states
      approach is used to compare the experimental results with predictions for a
      reference system of charged hard spheres in a dielectric continuum. Topics of
      special interest are the formation of ion pairs and larger ion clusters in dilute
      solutions and their fate at high concentrations, where they have to redissociate
      in the excess ionic liquid to form the charge-ordered structure of the fused
      salt. In solvents of low polarity this transition leads to electrical conductance
      minima and liquid-liquid immiscibilities.

PMID- 22455033
TI  - Measurements of the complete solvation response of coumarin 153 in ionic liquids
      and the accuracy of simple dielectric continuum predictions.
AB  - The complete solvation response of coumarin 153 (C153) has been determined over
      the range 10(-13)-10(-8) s in a variety of ionic liquids by combining femtosecond
      broad-band fluorescence upconversion and picosecond time-correlated single photon
      counting measurements. These data are used together with recently reported
      dielectric data in eight ionic liquids to test the accuracy of a simple continuum
      model for predicting solvation dynamics. In most cases the features of the
      solvation response functions predicted by the dielectric continuum model are
      similar to the measured dynamics of C153. The predicted dynamics are, however,
      systematically faster than those observed, on average by a factor of 3-5.
      Computer simulations of a model solute/ionic liquid system also exhibit the same
      relationship between dielectric predictions and observed dynamics. The
      simulations point to spatial dispersion of the polarization response as an
      important contributor to the over-prediction of solvation rates in ionic liquids.

PMID- 22455034
TI  - High pressure studies of the transport properties of ionic liquids.
AB  - High pressure measurements have been made of viscosities, ion self-diffusion
      coefficients and electrical conductivities of ionic liquids, mainly of
      imidazolium salts. We review how these properties have been analysed in terms of
      the empirical Stokes-Einstein, Walden and Nernst-Einstein equations, and examine
      trends revealed by the phenomenological approach of velocity correlation
      coefficients and the more general theory of density scaling. Finally we examine
      the possibility of dynamic crossover in the transport properties of ionic
      liquids.

PMID- 22455035
TI  - Gold. Preface.

PMID- 22455036
TI  - Spiers Memorial Lecture. Role of perimeter interfaces in catalysis by gold
      nanoparticles.
AB  - Gold can be deposited as nanoparticles (NPs) of 2 to 5 nm in diameter on a
      variety of materials such as metal oxides and carbides, carbons, organic polymers
      and exhibits surprisingly high catalytic activities for many reactions in both
      gas and liquid phases. The mechanisms for the genesis of catalysis by gold NPs is
      discussed based on real powder catalysts and model single crystal catalysts for
      two simple reactions, low-temperature oxidation of CO in which gold NPs catalysts
      are exceptionally active and for dihydrogen dissociation in which gold NPs
      catalysts are still poorly active. For both the two reactions, it has been
      revealed that reactions take place at perimeter interfaces around gold NPs.

PMID- 22455038
TI  - The active site behaviour of electrochemically synthesised gold nanomaterials.
AB  - Even though gold is the noblest of metals, a weak chemisorber and is regarded as
      being quite inert, it demonstrates significant electrocatalytic activity in its
      nanostructured form. It is demonstrated here that nanostructured and even
      evaporated thin films of gold are covered with active sites which are responsible
      for such activity. The identification of these sites is demonstrated with
      conventional electrochemical techniques such as cyclic voltammetry as well as a
      large amplitude Fourier transformed alternating current (FT-ac) method under
      acidic and alkaline conditions. The latter technique is beneficial in determining
      if an electrode process is either Faradaic or capacitive in nature. The observed
      behaviour is analogous to that observed for activated gold electrodes whose
      surfaces have been severely disrupted by cathodic polarisation in the hydrogen
      evolution region. It is shown that significant electrochemical oxidation
      responses occur at discrete potential values well below that for the formation of
      the compact monolayer oxide of bulk gold and are attributed to the facile
      oxidation of surface active sites. Several electrocatalytic reactions are
      explored in which the onset potential is determined by the presence of such sites
      on the surface. Significantly, the facile oxidation of active sites is used to
      drive the electroless deposition of metals such as platinum, palladium and silver
      from their aqueous salts on the surface of gold nanostructures. The resultant
      surface decoration of gold with secondary metal nanoparticles not only indicates
      regions on the surface which are rich in active sites but also provides a method
      to form interesting bimetallic surfaces.

PMID- 22455037
TI  - Gold nanoparticle-polymer/biopolymer complexes for protein sensing.
AB  - Nanoparticle-based sensor arrays have been used to distinguish a wide range of
      biomolecular targets through pattern recognition. Such biosensors require
      selective receptors that generate a unique response pattern for each analyte. The
      tunable surface properties of gold nanoparticles make these systems excellent
      candidates for the recognition process. Likewise, the metallic core makes these
      particles fluorescence superquenchers, facilitating transduction of the binding
      event. In this report we analyze the role of gold nanoparticles as receptors in
      differentiating a diversity of important human proteins, and the role of the
      polymer/biopolymer fluorescent probes for transducing the binding event. A
      structure-activity relationship analysis of both the probes and the nanoparticles
      is presented, providing direction for the engineering of future sensor systems.

PMID- 22455039
TI  - Aberration corrected analytical electron microscopy studies of sol-immobilized Au
      + Pd, Au{Pd} and Pd{Au} catalysts used for benzyl alcohol oxidation and hydrogen
      peroxide production.
AB  - In this study, a systematic series of AuPd bimetallic particles were prepared by
      colloidal synthesis methods, in order to gain better control over the particle
      size distribution and structure. Particles having random alloy structures, as
      well as 'designer' particles with Pd-shell/Au-core and Au-shell/Pd-core
      morphologies, have been prepared and immobilized on both activated carbon and
      TiO2 supports. Aberration corrected analytical electron microscopy (ACEAM) has
      been extensively used to characterize these sol-immobilized materials. In
      particular, state-of-the-art z-contrast STEM-HAADF imaging and STEM-XEDS spectrum
      imaging has been employed. These techniques have provided invaluable new (and
      often unexpected) information on the atomic structure, elemental distribution
      within particles, and compositional variations between particles for these
      controlled catalyst preparations. In addition, we have been able to compare their
      differing thermal stability, sintering and wetting behaviors on activated carbon
      and TiO2 supports. These sol immobilized materials have also been compared as
      catalysts for (i) benzyl alcohol oxidation and (ii) the direct production of H2O2
      in an attempt to elucidate the optimum particle morphology/ support combination
      for each reaction.

PMID- 22455040
TI  - Nanoporous gold: a new gold catalyst with tunable properties.
AB  - Nanoporous gold (np-Au) represents a novel nanostructured bulk material with very
      interesting perspectives in heterogeneous catalysis. Its monolithic porous
      structure and the absence of a support or other stabilizing agents opens up
      unprecedented possibilities to tune structure and surface chemistry in order to
      adapt the material to specific catalytic applications. We investigated three of
      these tuning options in more detail: change of the porosity by annealing,
      increase of activity by the deposition of oxides and change of activity and
      selectivity by bimetallic effects. As an example for the latter case, the effect
      of Ag impurities will be discussed. The presence and concentration of Ag can be
      correlated to the availability of active oxygen. While for the oxidation of CO
      the activity of the catalyst can be significantly enhanced when increasing the
      content of Ag, we show for the oxidation of methanol that the selectivity is
      shifted from partial to total oxidation. In a second set of experiments, two
      different metal-oxides were deposited on np-Au, praseodymia and titania. In both
      cases, the surface chemistry changed significantly. The activity of the catalyst
      for oxidation of CO was increased by up to one order of magnitude after
      modification. Finally, we used adsorbate controlled coarsening to tune the
      structure of np-Au. In this way, even gradients in the pore- and ligament size
      could be induced, taking advantage of mass transport phenomena.

PMID- 22455041
TI  - New insight into mechanisms in water-gas-shift reaction on Au/CeO2(111): a
      density functional theory and kinetic study.
AB  - Using density functional theory (DFT) and kinetic analyses, a new carboxyl
      mechanism for the water-gas-shift reaction (WGSR) on Au/CeO2(111) is proposed.
      Many elementary steps in the WGSR are studied using an Au cluster supported on
      CeO2(111). It is found that (i) water can readily dissociate at the interface
      between Au and CeO2; (ii) CO2 can be produced via two steps: adsorbed CO on the
      Au cluster reacts with active OH on ceria to form the carboxyl (COOH) species and
      then COOH reacts with OH to release CO2; and (iii) two adsorbed H atoms recombine
      to form molecular H2 on the Au cluster. Our kinetic analyses show that the
      turnover frequency of the carboxyl mechanism is consistent with the experimental
      one while the rates of redox and formate mechanisms are much slower than that of
      carboxyl mechanism. It is suggested that the carboxyl pathway is likely to be
      responsible for WGSR on Au/CeO2.

PMID- 22455042
TI  - A periodic DFT study of the activation of O2 by Au nanoparticles on alpha-Fe2O3.
AB  - Oxidation chemistry with supported Au nanoparticles as catalysts is an area of
      intense research. Even so there is still much discussion as to the nature of Au
      species generated on the complex surfaces of these catalysts and the types of
      oxygen species that are present. Recent experimental work has highlighted Au bi
      layers with dimensions of 0.5 nm supported on iron oxide as a very efficient
      catalyst system for CO oxidation. This size scale implies clusters containing
      only 10 Au atoms, making the simulation of the nanoparticles, oxide surface and
      their interface amenable to perioidic density functional theory calculations. We
      present simulation results which demonstrate that the dissociation of O2 is
      energetically favourable at the interface between nanoparticle and oxide, with
      both surface Fe cations and Au atoms taking part in the adsorption site. Here the
      barrier to dissociation of O2 is found to be lower than the energy required for
      molecular desorption which is not the case for isolated Au clusters. This
      reaction also produces oxidised Au atoms, as confirmed by Bader charge analysis.
      For isolated clusters we show that such oxidised Au species give rise to empty d
      band states, whereas molecular adsorption of O2 does not.

PMID- 22455043
TI  - Free gold clusters: beyond the static, monostructure description.
AB  - The thermodynamical stability of free, pristine gold clusters at finite
      temperature, and of cluster+ligands complexes at finite temperature and in the
      presence of an atmosphere composed of O2 and CO, is studied employing parallel
      tempering and ab initio atomistic thermodynamics. We focus on Au13, which
      displays a significant fluxional behavior: Even at low temperature (100 K) this
      cluster exhibits a multitude of structures that dynamically transform into each
      other. At finite temperature, the preference of this cluster for three
      dimensional versus planar structures is found to result from entropic effects.
      For gold clusters containing one to four gold atoms in an O2 + CO atmosphere, we
      apply ab initio atomistic thermodynamics. On the basis of these considerations,
      we single out a likely reaction path for CO oxidation catalyzed by gold clusters.

PMID- 22455044
TI  - Aurophilic attractions between a closed-shell molecule and a gold cluster.
AB  - The attractions between a closed-shell gold cluster and a closed-shell Au(I)
      molecule are theoretically studied, and related to monomer properties. The
      results suggest that the Au(I) mainly interacts with the nearest gold atoms and
      that the interaction is roughly proportional to the number of nearest neighbours.
      Different functionals are compared. The SCS-MP2 results are close to the CCSD (T)
      ones for the systems studied. The question of ionic contributions to the
      stability of 'staple' structures is raised.

PMID- 22455045
TI  - Theoretical insights into the superior activity of gold catalysts and reactions
      of organogold intermediates with electrophiles.
AB  - Three fundamental steps of homogeneous gold catalysis, the activiation of
      substrates by coordination to gold, the protodeauration after the nucleophilic
      addition and the transmetalation to palladium in palladium-catalysed C-C bond
      forming reactions using organogold intermediates have been studied and discussed
      in detail.

PMID- 22455046
TI  - A computational investigation of H2 adsorption and dissociation on Au
      nanoparticles supported on TiO2 surface.
AB  - The specific role played by small gold nanoparticles supported on the rutile
      TiO2( 110) surface in the processes of adsorption and dissociation of H2 is
      discussed. It is demonstrated that the molecular and dissociative adsorption of
      H2 on Au(n) clusters containing n = 1, 2, 8 and 20 atoms depends on cluster size,
      geometry structure, cluster flexibility and the interaction with the support
      material. Rutile TiO2(110) support energetically promotes H2 dissociation on gold
      clusters. It is demonstrated that the active sites towards H2 dissociation are
      located at corners and edges on the surface of the gold nanoparticle in the
      vicinity of the support. The low coordinated oxygen atoms on the TiO2(110)
      surface play a crucial role for H2 dissociation. Therefore the catalytic activity
      of a gold nanoparticle supported on the rutile TiO2(110) surface is proportional
      to the length of the perimeter interface between the nanoparticle and the
      support.

PMID- 22455047
TI  - Insights into catalysis by gold nanoparticles and their support effects through
      surface science studies of model catalysts.
AB  - One important aid in understanding catalysis by gold nanoparticles would be to
      understand the strength with which they bond to different support materials and
      the strength with which they bond adsorbed intermediates, and how these strengths
      depend on nanoparticle size. We present here new measurements of adsorption
      energies by single crystal adsorption calorimetry, and new analyses of other
      recent measurements by this technique in our lab, which imply that: (1) small
      nanoparticles of metals like Au bind much more strongly to supports like titania
      and iron oxide which are generally observed to be effective in making Au
      nanoparticles active in catalysis than to supports like MgO which are considered
      less effective, (2) the thermodynamic stability of adsorbed intermediates for
      catalytic reactions can either increase strongly or decrease strongly with
      decreasing metal nanoparticle size below 8 nm, depending on the system, and (3)
      the reaction to insert O2 into the Au-H bond of adsorbed H on the Au(111) surface
      to make Au-OOH (O2,g + H(ad) --> OOH(ad)) is exothermic by -80 kJ mol(-1). This
      adsorbed hydroperoxy species is thought to be a key intermediate in selective
      oxidation reactions over Au nanoparticle catalysts, but its production by this
      reaction may also provide a route for O2 activation in less demanding reactions
      (like CO oxidation) as well. Its stability would be even higher on Au
      nanoparticles below 3 nm in diameter, but even there it is too unstable to be
      formed by combining adsorbed OH with an O adatom (OH(ad) + O(ad) --> OOH(ad)),
      which is estimated to be endothermic by 175 kJ mol(-1). The implications of the
      stability of metal nanoparticles versus particle size on different supports and
      of the stability and potential reactions of OOH(ad) in Au catalysis will be
      discussed.

PMID- 22455048
TI  - A paradigm for predicting selective oxidation on noble metals: oxidative
      catalytic coupling of amines and aldehydes on metallic gold.
AB  - We demonstrate in the present work that relatively straightforward acid/base
      principles of surface reactivity predict oxygen-assisted amine-aldehyde coupling
      on metallic gold. Formed via the oxygen-assisted (Bronsted acid) N-H bond
      activation of dimethylamine, (CH3)2N(a) acts as a nucleophile to couple with
      various aldehydes, forming the corresponding amides. At low initial coverages of
      oxygen on the surface very high selectivities are achieved. The reaction proceeds
      via the surface-bound hemiaminal intermediate, which beta-hydride eliminates well
      below room temperature to form the amide product. On metallic gold desorption of
      the amide appears to be the rate-limiting step. Under the transient conditions
      employed in this work oxygen-assisted coupling of the amine with alcohols is
      limited, suggesting that such reactions must be conducted in the steady state in
      order to have both the aldehyde and adsorbed (CH3)2N(a) present simultaneously.

PMID- 22455049
TI  - Catalytic properties of supported gold nanoparticles: new insights into the size
      activity relationship gained from in operando measurements.
AB  - The relationship between the catalytic activity and the size was studied in
      operando in the case of gold nanoparticles on TiO2(110) model catalyst during
      carbon monoxide oxidation. The geometrical parameters, the shape and the
      dispersion of the particles on the oxide support were examined in detail. The
      catalytic activity was found optimum for a nanoparticle diameter of about 2 nm
      and a height of six atomic monolayers. Above the maximum, it fits a power law of
      the diameter D(-24 +/- 0.3). This indicates that the low-coordinated sites play a
      major role in the catalytic activity, however such a model still fails to explain
      the activity maximum. The nanoparticle sintering was also investigated since it
      is suspected of being responsible for the decrease of the catalyst activity in
      the course of time. It was clearly observed for particles with a size around the
      maximum of activity and smaller. At the very beginning of the CO conversion into
      CO2, the sintering is strongly activated. The nanoparticles mobility is dependent
      upon the TiO2(110) surface direction under consideration: it is higher along the
      [001]TiO2 than along the [1-10]TiO2. Then, the sintering greatly slows down. This
      could be explained by a nanoparticles' pinning at the step edges. The thermal
      energy released by the exothermic CO oxidation reaction was evaluated and it
      suggests that the sintering results from a more complex process than from a
      reaction-induced local heating.

PMID- 22455050
TI  - Exploring the structure and chemical activity of 2-D gold islands on graphene
      moire/Ru(0001).
AB  - Au deposited on Ru(0001)-supported extended, continuous graphene moire forms
      large 2-D islands at room temperature that are several nanometers in diameter but
      only 0.55 nm in height, in the apparent absence of typical binding sites such as
      defects and adsorbates. These Au islands conform to the corrugation of the
      underlying graphene and display commensurate moire patterns. Several extended Au
      structure models on graphene/Ru(0001) are examined using density functional
      theory calculations. Close-packed Au overlayers are energetically more stable,
      but all interact weakly with the support. Preliminary tests found the Au
      islands/graphene/Ru(0001) surface to be active for CO oxidation at cryogenic
      temperature, which suggests that the Au itself is the locus of catalytic
      activity.

PMID- 22455051
TI  - The effect of the metal to non-metal transition on the activity of gold
      catalysts.
AB  - The problem of obtaining exact information on the particle size dependence of the
      rate of gold-catalysed reactions is surveyed, and it is shown to be possible that
      over a range of mean sizes the activity for CO oxidation is predominantly due to
      the fraction of particles smaller than about 2.5 nm. This size coincides with the
      point at which transition from metallic to non-metallic or 'molecular' behaviour
      is expected, and means of describing the electronic structure of the
      microparticles is considered. This transition may be the cause of enhanced and
      activated chemisorption of the CO molecule. Analysis of results for the rate
      dependence on size for CO oxidation on Au/TiO2 catalysts by the compensation
      relation confirms the importance of the transition. It is also held responsible
      for the ability of the PtAu system to form small homogeneous alloy particles.

PMID- 22455052
TI  - Oxidative coupling of alcohols on gold: insights from experiments and theory.
AB  - Molecular level understanding of the mechanism of oxidative coupling of alcohols
      on metallic Au(111) activated by oxygen is achieved through a combination of
      experiments and theoretical calculations. The facility of the beta-H elimination
      of the alkoxys, which increases with the length of the alkyl chain, is identified
      to be critical in determining the product distributions. Dioxymethylene serves as
      a formaldehyde reservoir in the cross-coupling reaction between methanol and
      formaldehyde through its reversible formation and decomposition, contributing to
      the high selectivity for the coupling products.

PMID- 22455053
TI  - Kinetic study of propylene epoxidation with H2 and O2 over Au/Ti-SiO2 in the
      explosive regime.
AB  - A kinetic study of propene epoxidation with hydrogen and oxygen over a Au/Ti-SiO2
      catalyst has been performed in a wide range of reactant concentrations including
      the explosive region in a micro reactor. The observed rate dependency on the
      reactants for the epoxidation and the competing direct water formation is
      discussed in relation to the current mechanistic insights in the literature. The
      formation rate of propene oxide is most dependent on the hydrogen concentration,
      in which the formation of an active peroxo species on the gold nanoparticles is
      the rate determining step. Deactivation is mainly caused by consecutive oxidation
      of propene oxide. Oxygen favours the regeneration of the deactivated catalytic
      sites. Water formation and propene epoxidation are strongly correlated. Water is
      formed via two routes: through the active peroxo intermediate responsible for
      epoxidation and from direct formation without involving this active intermediate.
      Improving the hydrogen efficiency should distinguish between these two routes of
      water formation. The active peroxo intermediate in epoxidation is competitively
      consumed by hydrogenation and epoxidation. The active gold site is blocked during
      deactivation.

PMID- 22455054
TI  - Methane activation and partial oxidation on free gold and palladium clusters:
      mechanistic insights into cooperative and highly selective cluster catalysis.
AB  - The catalytic activation, dehydrogenation, and direct oxidative conversion of
      methane into more valuable products such as larger hydrocarbons, alcohols,
      aldehydes etc. are of considerable industrial interest. To investigate the
      energetics and kinetics of elementary bond-breaking and bond-formation processes,
      free metal clusters can serve as versatile catalytic model systems. In this
      context, temperature dependent reactions of small cationic gold clusters Au(x)+
      with methane as well as a mixture of methane and molecular oxygen have been
      performed in an octopole ion trap under multi-collision conditions and compared
      with the corresponding reactions on palladium clusters Pd(x)+ (x = 2-4). Binding
      energies of methane to all investigated cluster cations are determined from
      kinetic measurements via statistical analysis. Furthermore, among the gold
      clusters, the dimer Au2+ is found to be able to dehydrogenate methane and to
      convert it into ethylene in a highly selective catalytic reaction. In contrast,
      all investigated palladium clusters activate methane under non-selective
      formation of a variety of dehydrogenated products. Most interestingly, methane
      dehydrogenation is observed for Pd(x)+ and Au2+ only, if a cluster specific
      'critical number' of methane molecules is pre-adsorbed. This emphasizes the
      importance of cooperative coadsorption effects in the dehydrogenation process on
      these clusters. Finally, the reaction between Au2+ and both O2 and CH4 yields a
      low temperature product of the stoichiometry Au2(C3H8O2)+ that clearly contains
      activated O2 and dehydrogenated methane indicating a possible C-O bond formation
      process. The palladium dimer Pd2+ on the other hand exhibits only the mere
      coadsorption of molecular oxygen and non-dehydrogenated methane.

PMID- 22455055
TI  - Gold catalyzed liquid phase oxidation of alcohol: the issue of selectivity.
AB  - Commercial carbon nanotubes (CNTs) and carbon nanofibers (CNFs) modified in
      various ways at the surface have been used as supports for gold nanoparticles
      (AuNPs) in order to study their influence on the activity/selectivity of
      catalysts in the aqueous oxidation of alcohol. Particularly oxidative treatment
      was used to introduce carboxylic functionalities, whereas subsequent treatment
      with NH3 at different temperatures (473 K, 673 K and 873 K) produced N-containing
      groups leading to an enhancement of basic properties as the NH3 treatment
      temperature was increased. The nature of the N-containing groups changed as the
      temperature increased, leading to an increase in the hydrophobicity of the
      support surface. Similar Au particle size and similar textural properties of the
      supports allowed the role of chemical surface groups in both the activity and the
      selectivity of the reaction of glycerol oxidation to be highlighted. An increase
      of basic functionalities produced a consistent increase in the activity of the
      catalyst, which was correlated to the promoting effect of the basic support in
      the alcoholate formation and the subsequent C-H bond cleavage. The selectivity
      towards primary oxidation products (C3 compounds) was the highest for the
      catalysts treated with NH3 at 873 K, which presented the most hydrophobic
      surface. The same trend in the catalyst activity has been obtained in the aqueous
      benzyl alcohol base-free oxidation. As in the case of glycerol, the increasing of
      basicity and/or hydrophobicity increased the consecutive reactions.

PMID- 22455056
TI  - Enhanced performance of the catalytic conversion of allyl alcohol to 3
      hydroxypropionic acid using bimetallic gold catalysts.
AB  - One of the strategic building blocks in organic synthesis is 3-hydroxypropionic
      acid, which is particularly important for the manufacture of high performance
      polymers. However, to date, despite many attempts using both biological and
      chemical routes, no large scale effective process for manufacturing 3
      hydroxypropionic acid has been developed. One potentially useful starting point
      is from allyl alcohol, as this can be obtained in principle from the dehydration
      of glycerol, thereby presenting a bio-renewable green pathway to this important
      building block. The catalytic transformation of allyl alcohol to 3
      hydroxypropionic acid presents interesting challenges in catalyst design,
      particularly with respect to the control of selectivity among the products that
      can be expected, as acrylic acid, acrolein and glyceric acid can also be formed.
      In this paper, we present a novel eco-sustainable catalytic pathway leading to 3
      hydroxypropionic acid, which highlights the outstanding potential of gold-based
      and bimetallic catalysts in the aerobic oxidation of allyl alcohol.

PMID- 22455057
TI  - Preparation of ultra low loaded Au catalysts for oxidation reactions.
AB  - Cyanide leaching was used to obtain Au/SiO2 catalysts with very low gold
      loadings. A number of catalysts with a nominal 5 wt% target loading were prepared
      using impregnation and deposition precipitation techniques and these were found
      to be active catalysts for the solvent-free aerobic oxidation of benzyl alcohol.
      Exposure of these catalysts to a basic solution of NaCN for 10 min leached gold
      from the materials to give very pale pink catalysts which were found to contain
      just 0.06 wt% Au. The concentration of Au removed from the catalyst was constant
      regardless of the length of NaCN exposure. When the cyanide leached materials
      were employed for benzyl alcohol oxidation under the same conditions as the
      unleached parent catalysts, the conversions were identical. However, when the
      catalytic activity was normalised to the Au content (determined by ICP analysis)
      the TOFs were much higher for the NaCN treated catalysts (> 400,000 h(-1)). These
      results clearly demonstrate that NaCN leaching is an effective route to the
      development of catalysts containing very low gold content, whilst maintaining
      high activity. The leached materials were found to comprise metallic Au
      nanoparticles. The successful utilisation of ultra low loaded Au catalysts for
      selective oxidation, where the majority of the Au present is active and 98% of
      the spectator Au is removed, makes the industrial application of such materials
      more economically viable. Information obtained through the identification of
      these active structures using state of the art techniques may provide useful
      insights into how the reaction proceeds on the Au surface.

PMID- 22455058
TI  - Concluding remarks: from match to flamethrower.
AB  - These remarks give some impressions of Faraday Discussion 152 from the point of
      view of an outsider and suggest a number of actions which might help bind the
      Gold Catalysis Community more strongly and increase the long term impact of their
      science.

PMID- 22455059
TI  - Hydrogen as a fuel for today and tomorrow: expectations for advanced hydrogen
      storage materials/systems research.
AB  - History shows that the evolution of vehicles is promoted by several environmental
      restraints very similar to the evolution of life. The latest environmental strain
      is sustainability. Transport vehicles are now facing again the need to advance to
      use sustainable fuels such as hydrogen. Hydrogen fuel cell vehicles are being
      prepared for commercialization in 2015. Despite intensive research by the world's
      scientists and engineers and recent advances in our understanding of hydrogen
      behavior in materials, the only engineering phase technology which will be
      available for 2015 is high pressure storage. Thus industry has decided to
      implement the high pressure tank storage system. However the necessity of smart
      hydrogen storage is not decreasing but rather increasing because high market
      penetration of hydrogen fuel cell vehicles is expected from around 2025 onward.
      In order to bring more vehicles onto the market, cheaper and more compact
      hydrogen storage is inevitable. The year 2025 seems a long way away but
      considering the field tests and large scale preparation required, there is little
      time available for research. Finding smart materials within the next 5 years is
      very important to the success of fuel cells towards a low carbon sustainable
      world.

PMID- 22455060
TI  - Pore with gate: modulating hydrogen storage in metal-organic framework materials
      via cation exchange.
AB  - A range of anionic metal-organic framework (MOF) materials has been prepared by
      combination of In(III) with tetracarboxylate isophthalate-based ligands. These
      materials incorporate organic cations, either H2ppz2+ (ppz = piperazine) or
      Me2NH2+, that are hydrogen bonded to the pore wall. These cations act as a gate
      controlling entry of N2 and H2 gas into and out of the porous host. Thus,
      hysteretic adsorption/desorption for N2 and H2 is observed in these systems,
      reflecting the role of the bulky hydrogen bonded organic cations in controlling
      the kinetic trapping of substrates. Post-synthetic cation exchange with Li+ leads
      to removal of the organic cation and the formation of the corresponding Li+
      salts. Replacement of the organic cation with smaller Li+ leads to an increase in
      internal surface area and pore volume of the framework material, and in some
      cases to an increase in the isosteric heat of adsorption of H2 at zero coverage,
      as predicted by theoretical modelling. The structures, characterisation and
      analysis of these charged porous materials as storage portals for H2 are
      discussed. Inelastic neutron scattering experiments confirm interaction of H2
      with the carboxylate groups of the isophthalate ligands bound to In(III) centres.

PMID- 22455061
TI  - The effect of host relaxation and dynamics on guest molecule dynamics in
      H2/tetrahydrofuranhydrate.
AB  - We use ab initio molecular dynamics simulations to obtain classically the effects
      of H2O cage motions on the potential-energy surface (PES) of encapsulated H2 in
      the H2/tetrahydrofuran-hydrate system. The significant differences between the
      PES for the H2 in rigid and flexible cages that we find will influence
      calculation of the quantum dynamics of the H2. Part of these differences arises
      from the relaxation of the H2O cage around the classical H2, with a second part
      arising from the coupling of both translational and rotational motions of H2 with
      the H20 cage. We find that isotopic substitution of 2H for 1H of the H2O cage
      affects the coupling, which has implications for experiments that require the use
      of 2H2O, including inelastic neutron scattering that uses 2H2O cages in order to
      focus on the H2 guest dynamics. Overall, this work emphasizes the importance of
      taking into account cage dynamics in any approach used to understand the dynamics
      of H2 guests in porous framework materials.

PMID- 22455062
TI  - The role of Ni in increasing the reversibility of the hydrogen release from
      nanoconfined LiBH4.
AB  - Nanoconfinement and the use of catalysts are promising strategies to enhance the
      reversibility of hydrogen storage in light metal hydrides. We combined
      nanoconfinement of LiBH4 in nanoporous carbon with the addition of Ni. Samples
      were prepared by deposition of 5-6 nm Ni nanoparticles inside the porous carbon,
      followed by melt infiltration with LiBH4. The Ni addition has only a slight
      influence on the LiBH4 hydrogen desorption, but significantly enhances the
      subsequent uptake of hydrogen under mild conditions. Reversible, but limited,
      intercalation of Li is observed during hydrogen cycling. X-ray diffraction shows
      that the initial crystalline 5-6 nm Ni nanoparticles are not present anymore
      after melt infiltration with LiBH4. However, transmission electron microscopy
      showed Ni-containing nanoparticles in the samples. Extended X-ray absorption fine
      structure spectroscopy proved the presence of Ni(x)B phases with the Ni-B
      coordination numbers changing reversibly with dehydrogenation and rehydrogenation
      of the sample. Ni(x)B can act as a hydrogenation catalyst, but solid-state 11B
      NMR proved that the addition of Ni also enhanced the reversibility of the system
      by influencing the microstructure of the nanoconfined LiBH4 upon cycling.

PMID- 22455063
TI  - Analysis of hydrogen storage in nanoporous materials for low carbon energy
      applications.
AB  - A robust, simple methodology for analysis of isotherms for the adsorption of
      fluids above their critical temperature onto nanostructured materials is
      presented. The analysis of hydrogen adsorption in a metal-organic framework is
      used as an example to illustrate the methodology, which allows the estimation of
      the absolute adsorption into nanoporous systems. Further advantages of employing
      this analysis are that adsorption systems can be described using a small number
      of parameters, and that excess and absolute isotherms can be extrapolated and
      used to predict adsorption behaviour at higher pressures and over different
      temperature ranges. Thermodynamic calculations, using the exact Clapeyron
      equation and the Clausius-Clapeyron approximation applied to the example dataset,
      are presented and compared. Conventional compression of hydrogen and adsorptive
      storage are evaluated, with an illustration of the pressure ranges in which
      adsorption facilitates storage of greater volumes of hydrogen than normal
      compression in the same operating conditions.

PMID- 22455064
TI  - Characterisation of porous hydrogen storage materials: carbons, zeolites, MOFs
      and PIMs.
AB  - Porous materials adsorb H2 through physisorption, a process which typically has a
      rather low enthalpy of adsorption (e.g. ca. 4 to 7 kJ mol(-1) for MOFs), thus
      requiring cryogenic temperatures for hydrogen storage. In this paper, we consider
      some of the issues associated with the accurate characterisation of the hydrogen
      adsorption properties of microporous materials. We present comparative
      gravimetric hydrogen sorption data over a range of temperatures for different
      microporous materials including an activated carbon, a zeolite, two MOFs and a
      microporous organic polymer. Hydrogen adsorption isotherms were used to calculate
      the enthalpy of adsorption as a function of hydrogen uptake, and to monitor the
      temperature dependence of the uptake of hydrogen. Under the conditions
      investigated, it was found that the Toth equation provided better fits to the
      absolute isotherms compared to the Sips (Langmuir-Freundlich) equation at low
      pressures, whereas it appeared to overestimate the maximum saturation capacity.
      The isosteric enthalpy of adsorption was calculated by either: fitting the Sips
      and Toth equations to the adsorption isotherms and then applying the Clausius
      Clapeyron equation; or by using a multiparameter Virial-type adsorption isotherm
      equation. It was found that the calculated enthalpy of adsorption depended
      strongly upon the method employed and the temperature and pressure range used. It
      is shown that a usable capacity can be calculated from the variable temperature
      isotherms for all materials by defining a working pressure range (e.g. 2 to 15
      bar) over which the material will be used.

PMID- 22455065
TI  - Synthesis of small metallic Mg-based nanoparticles confined in porous carbon
      materials for hydrogen sorption.
AB  - MgH2, Mg-Ni-H and Mg-Fe-H nanoparticles inserted into ordered mesoporous carbon
      templates have been synthesized by decomposition of organometallic precursors
      under hydrogen atmosphere and mild temperature conditions. The hydrogen
      desorption properties of the MgH2 nanoparticles are studied by thermo-desorption
      spectroscopy. The particle size distribution of MgH2, as determined by TEM, is
      crucial for understanding the desorption properties. The desorption kinetics are
      significantly improved by downsizing the particle size below 10 nm. Isothermal
      absorption/desorption cycling of the MgH2 nanoparticles shows a stable capacity
      over 13 cycles. The absorption kinetics are unchanged though the desorption
      kinetics are slower on cycling.

PMID- 22455066
TI  - The effect of complex halides and binary halides on hydrogen release for the
      2LiBH4:1MgH2 system.
AB  - Due to the high hydrogen capacity of LiBH4, various strategies have been
      investigated to improve the hydrogen release properties of LiBH4. Theoretical
      calculations suggest that doping LiBH4 with F-/CI- anions may generate lattice
      substitutions (such as the formation of LiBH3F or LiBH2F2), which will lower the
      hydrogen release temperature from LiBH4. The effect of addition of F-/Cl
      containing dopants (viz. LiBF4, NH4F, LiA1Cl4 and NH4Cl) on the hydrogen release
      from 2LiBH4:1MgH2 was investigated and LiBF4 was found to be the most effective
      among the dopants studied. Furthermore, the combined effect of LiBF4 and the
      catalyst precursor NbF5 was studied on the hydrogen release from 2LiBH4:1MgH2. It
      was found that the hydrogen release temperature for the LiBH4 and MgH2 components
      were substantially reduced by 55 degrees C and 112 degrees C respectively by the
      combined doping and catalytic effect from LiBF4 and NbF5. This sample was
      partially rehydrogenated under 400 degrees C and 100 bar, and upon cycling the
      hydrogen release temperature was lowered further for the LiBH4 component but
      increased for the MgH2 component.

PMID- 22455067
TI  - Incorporating magnesium and calcium cations in porous organic frameworks for high
      capacity hydrogen storage.
AB  - We propose incorporating a bi-functional group consisting of magnesium or calcium
      cations and a 1,2,4,5-benzenetetroxide anion (C6H2O4(4-)) in porous materials to
      enhance the hydrogen storage capacity. The C6H2O4M2 bifunctional group is highly
      stable and polarized, and each group provides 18 (M = Mg) or 22 (M = Ca) binding
      sites for hydrogen molecules with an average binding energy of ca. 10 kJ mol(-1)
      per hydrogen molecule based on RIMP2/ TZVPP calculations. Two porous materials
      (PAF-Mg or PAF-Ca) constructed with the bi-functional groups show remarkable
      improvement in hydrogen uptakes at normal ambient conditions. At 233 K and 10
      MPa, the predicted gravimetric uptakes are 6.8 and 6.4 wt% for PAF-Mg and PAF-Ca
      respectively. This work reveals that fabricating materials with large numbers of
      binding sites and relatively low binding energies is a promising approach to
      achieve high capacity for on-board storage of hydrogen.

PMID- 22455068
TI  - Control of hydrogen release and uptake in amine borane molecular complexes:
      thermodynamics of ammonia borane, ammonium borohydride, and the diammoniate of
      diborane.
AB  - Molecular complexes of Lewis acid-base pairs can be used to activate molecular
      hydrogen for applications ranging from hydrogen storage for fuel cells to
      catalytic hydrogenation reactions. In this paper, we examine the factors that
      determine the thermodynamics of hydrogen activation of a Lewis acid-base pair
      using the pedagogical examples of ammonia borane (NH3BH3, AB) and ammonium
      borohydride ([NH4][BH4], ABH2). At ambient temperatures, ABH2 loses hydrogen to
      form the Lewis acid-base complex AB, suggesting that free energy drives the
      reaction to release hydrogen. However, direct measurement of the reaction
      enthalpy is not straightforward given the complex decomposition pathways leading
      to the formation of the diammoniate of diborane ([NH3BH2NH3][BH4], DADB). In this
      work, we compare two approaches for deriving the thermodynamic relationships
      among AB, DADB, and ABH2.

PMID- 22455069
TI  - Probing the binding and spatial arrangement of molecular hydrogen in porous hosts
      via neutron Compton scattering.
AB  - The adsorption of molecular hydrogen (H2) in the alkali-graphite intercalate KC24
      has been studied using simultaneous neutron diffraction and Compton scattering.
      Neutron Compton scattering data for the (H2)xKC24 system (x = 0-2.5) were
      measured at T = 1.5 K as a function of the relative orientation between the
      neutron beam and the intercalate c-axis. Synchronous with the above proton-recoil
      measurements, high-resolution diffraction patterns were measured in
      backscattering geometry. From these diffraction measurements, the intrinsic
      mosaicity of the Papyex-based intercalate was determined to be approximately 15
      degrees half-width-at-half-maximum, in good agreement with previous studies
      [Finkelstein et al., Physica B, 2000, 291, 213]. Hydrogen uptake by the
      intercalate leads to a distinct and readily detectable broadening of the
      isotropic Compton profile compared to bulk H2, indicative of an enhanced
      interaction of the H2 molecule with the surrounding solid-state environment.
      Total proton-recoil intensities also scale linearly with the amount of adsorbed
      hydrogen. Taking as our starting point previous experimental and theoretical
      results, the isotropic widths of the proton momentum distributions can be
      explained on the basis of three energy scales, namely, intramolecular H-H
      vibrations, followed by H-H librations and H2 centre-of-mass translations. From
      the coverage dependence of these neutron data, we also establish an upper bound
      of approximately 10 meV for intermolecular hydrogen-hydrogen interactions.
      Finally, we observe a weak anisotropy of the width of the proton momentum
      distributions. Comparison of these experimental data with first-principles
      predictions indicates that subtle quantum mechanical effects associated with
      particle delocalisation and exchange lie at the heart of the observed behaviour.
      Overall, these results demonstrate the suitability and largely untapped potential
      of neutron Compton scattering to explore H2 uptake by solid-state hosts.

PMID- 22455070
TI  - Mobility and dynamics in the complex hydrides LiAlH4 and LiBH4.
AB  - The dynamics and bonding of the complex hydrides LiBH4 and LiAlH4 have been
      investigated by vibrational spectroscopy. The combination of infrared, Raman, and
      inelastic neutron scattering (INS) spectroscopies on hydrided and deuterided
      samples reveals a complete picture of the dynamics of the BH4- and AlH4 anions
      respectively as well as the lattice. The straightforward interpretation of
      isotope effects facilitates tracer diffusion experiments revealing the diffusion
      coefficients of hydrogen containing species in LiBH4, and LiAlH4. LiBH4 exchanges
      atomic hydrogen starting at 200 degrees C. Despite having an iso-electronic
      structure, the mobility of hydrogen in LiAlH4 is different from that of LiBH4.
      Upon ball-milling of LiAlH4 and LiAlD4, hydrogen is exchanged with deuterium even
      at room temperature. However, the exchange reaction competes with the
      decomposition of the compound. The diffusion coefficients of the alanate and
      borohydride have been found to be D approximately equal 7 x 10(-14) m2 s(-1) at
      473 K and D approximately equal 5 x 10(-16) m2 s(-1) at 348 K, respectively. The
      BH4 ion is easily exchanged by other ions such as I- or by NH2-. This opens the
      possibility of tailoring physical properties such as the temperature of the phase
      transition linked to the Li-ion conductivity in LiBH4 as measured by nuclear
      magnetic resonance and Raman spectroscopy. Temperature dependent Raman
      measurements on diffusion gradient samples Li(BH4)1-cIc demonstrate that
      increasing temperature has a similar impact to increasing the iodide
      concentration c: the system is driven towards the high-temperature phase of
      LiBH4. The influence of anion exchange on the hydrogen sorption properties is
      limited, though. For example, Li4(BH4)(NH2)3 does not exchange hydrogen easily
      even in the melt.

PMID- 22455072
TI  - Theoretical study of the vibrational properties of NaAlH4 with AlH3 vacancies.
AB  - It has been suggested that the diffusion of AlH3 vacancies plays an essential
      role in the decomposition of NaAlH4, a prototypical material for hydrogen
      storage. We find from first-principles calculations that the AlH3 vacancy induces
      several isolated vibrational modes that are highly localized in the vacancy
      region with frequencies within the phonon gaps of pure NaAlH4 in both the alpha
      and gamma phases. Thus, the proposed existence of AlH3 vacancies in the
      dehydrogenation reaction of NaAlH4 can be possibly confirmed with the
      experimental detection of these unique vibrational modes associated with the AlH3
      vacancy.

PMID- 22455071
TI  - Novel sodium aluminium borohydride containing the complex anion [Al(BH4,Cl)4]-.
AB  - The synthesis of a novel alkali-metal aluminium borohydride NaAl(BH4)xCl4-x from
      NaBH4 and AlCl3 using a solid state metathesis reaction is described. Structure
      determination was carried out using synchrotron powder diffraction data and
      vibrational spectroscopy. An orthorhombic structure (space group Pmn2(1)) is
      formed which contains Na+ cations and complex [Al(BH4,Cl)4]- anions. Due to the
      high chlorine content (1 < or = x < or = 1.43) the hydrogen density of the
      borohydride is only between 2.3 and 3.5 wt.% H2 in contrast to the expected 14.6
      wt.% for chlorine free NaAl(BH4)4. The decomposition of NaAl(BH4)xCl4-x is
      observed in the target range for desorption at about 90 degrees C by differential
      scanning calorimetry (DSC), in situ Raman spectroscopy and synchrotron powder X
      ray diffraction. Thermogravimetric analysis (TG) shows extensive mass loss
      indicating the loss of H2 and B2H6 at about 90 degrees C followed by extensive
      weight loss in the form of chloride evaporation.

PMID- 22455073
TI  - Synthesis of LiNH2 + LiH by reactive milling of Li3N.
AB  - The hydrogen sorption properties of Li3N under reactive milling conditions have
      been investigated in- and ex-situ as a function of polytype structure (alpha vs.
      beta), focusing on the influence of the micro-structure and/or the crystal
      structure upon hydrogen uptake. LiNH2 and LiH were synthesized by reactive
      milling of Li3N at 20 bar hydrogen pressure for 4 h. Reactive milling represents
      a quick and effective technique to produce LiNH2 by hydrogenation of Li3N at low
      hydrogen pressure and without any need for heating. As to our knowledge, we
      present a full hydrogenation of Li3N under the aforementioned conditions for the
      first time. The (de)hydrogenation and rehydrogenation behaviour of milled amides
      was evaluated using a combination of powder X-ray diffraction, differential
      scanning calorimetry, thermogravimetry and in situ Raman spectroscopy. In situ
      Raman spectroscopy showed a shift in the lithium amide stretching modes upon
      hydrogenation supporting a non-stoichiometric storage mechanism consistent with
      the literature. The microstructure and polytype composition of the Li3N
      dehydrogenated materials had no effect on the hydrogenation products and only
      minor effects on the hydrogen uptake profile during milling.

PMID- 22455074
TI  - In situ powder neutron diffraction study of non-stoichiometric phase formation
      during the hydrogenation of Li3N.
AB  - The hydrogenation of Li3N at low chemical potential has been studied in situ by
      time-of-flight powder neutron diffraction and the formation of a non
      stoichiometric Li4-2xNH phase and Li4NH observed. The results are interpreted in
      terms of a model for the reaction pathway involving the production of Li4NH and
      Li2NH, which subsequently react together to form Li4-2xNH. Possible mechanisms
      for the production of Li4NH from the hydrogenation of Li3N are discussed.

PMID- 22455075
TI  - Hydrogen storage and ionic mobility in amide-halide systems.
AB  - We report the results of a systematic study of the effect of halides on hydrogen
      release and uptake in lithium amide and lithium imide, respectively. The reaction
      of lithium amide and lithium imide with lithium or magnesium chloride, bromide
      and iodide resulted in a series of amide-halide and imide-halide phases, only two
      of which have been reported previously. On heating with LiH or MgH2, the amide
      halides synthesised all released hydrogen more rapidly than lithium amide itself,
      accompanied by much reduced, or in some cases undetectable, release of ammonia by
      product. The imide-halides produced were found to hydrogenate more rapidly than
      lithium imide, reforming related amide-halide phases. The work was initiated to
      test the hypothesis that the incorporation of halide anions might improve the
      lithium ion conductivity of lithium amide and help maintain high lithium ion
      mobility at all stages of the de/rehydrogenation process, enhancing the bulk
      hydrogen storage properties of the system. Preliminary ionic conductivity
      measurements indicated that the most conducting amide- and imide-halide phases
      were also the quickest to release hydrogen on heating and to hydrogenate. We
      conclude that ionic conductivity may be an important parameter in optimising the
      materials properties of this and other hydrogen storage systems.

PMID- 22455076
TI  - Homogeneous dehydrogenation of liquid organic hydrogen carriers catalyzed by an
      iridium PCP complex.
AB  - The activity of the PCP pincer complex IrH2{C6H3-2,6-(OPBu(t)2)2)}, (3) as a
      catalyst for the dehydrogenation of the potential liquid organic hydrogen
      carriers: perhydro-dibenzofuran (4), perhydro-indole (5), N-methyl perhydro
      indole (6), 4,4'-bipiperridine (7), 4-amino-methylpiperridine (8), and
      aminomethylcyclohexane (9) was investigated. Only low levels of dehydrogenation
      were achieved with 4 at 150 and 200 degrees C except in the presence a hydrogen
      acceptor, 3,3-dimethyl-1-butene (tbe). At temperatures above 150 degrees C, 3
      showed high activity with 5 but only for the release of H2 across the C-N bond.
      Dehydrogenation of 6 at 150 degrees C was found to release up to 2.9 wt% H2,
      giving N-methyl tetrahydroindole in 92% yield, but only 7% N-methyl indole.
      However, efficient dehydrogenation of the aliphatic hydrogens occurred at 200
      degrees C giving mixtures that approached a approximately 1:3 equilibrium between
      N-methyl indole and N-methyl tetrahydroindole at longer reaction times. The
      pincer catalyst was observed to be effective for the dehydrogenation of 7 and 8
      at 200 degrees C but the products polymerize. The catalytic dehydrogenation of 9
      was very efficient at 200 degrees C but gave primarily the undesired products
      dibenzylamine (68%), benzylidenebenzylamine (22%), ammonia and only minor amount
      of benzonitrile (10%). At 160 degrees C, 85% of the substrate was consumed after
      24 h of heating but only a minor amount of cyclohexanecarbonitrile (2%) was
      detected with the major products being biscyclohexylmethylamine (45%) and
      cyclohexylmethyl-cyclohexylimine (38%). The nitrile yield is remarkably improved
      to 97% when the dehydrogenation was carried out at 160 degrees C in the presence
      of 10 mol% NaOBu(t) but heating the reaction mixtures containing the base to 200
      degrees C resulted in the decomposition of the pincer catalyst.

PMID- 22455077
TI  - YMn2Hx and RMn(2-y)Fe(y)H6 (R = Y, Er) studied by Raman, infrared and inelastic
      neutron scattering spectroscopies.
AB  - YMn2 forms either interstitial YMn2Hx hydrides for x < or = 4.5 or a complex
      YMn2H6 hydride when submitted to high hydrogen pressure. These compounds have
      been studied by inelastic neutron scattering (INS) in order to clarify the
      different modes of H vibration. The INS spectra of YMn2Hx hydrides are strongly
      dependent on the H content. YMn2H6 and YMn2D6 show broad bands, also observed by
      Raman and IR spectroscopy, assigned to H-Mn-H (or D) and Mn-H bending and
      stretching modes. Both ErMn2D6 and ErMn1.8Fe0.2D6 show, in addition to the H
      vibration mode, an intense band at 215 cm(-1) which has been attributed to a
      magnetic excitation of Er3+ in view of its momentum transfer dependence.

PMID- 22455078
TI  - Hydride formation in Mg-based systems processed by reactive milling.
AB  - The possibilities to produce quaternary Mg-based transition-metal complex
      hydrides have been explored. Mg2Mn1--xFex (x = 0.5, 0) elemental powder mixtures
      were ball milled in a reactive D2 atmosphere (about 5 MPa). The results were
      compared with the formation of Mg2(FeD6)0.5(CoD5)0.5 from Mg-Fe-Co powders. The
      changes of D2 pressure were monitored during milling and deuterium absorption was
      detected within the first 15 h of milling. Powder X-ray and neutron diffraction
      analysis for the as-milled Mg2Mn0.5Fe0.5 powder showed a large fraction of
      unreacted elemental Mn, as well as the formation of a cubic K2PtCl6-type phase (a
      = 6.452 A). The latter could be identified as Mg2FeD6. Infrared spectroscopy
      confirmed the presence of [FeD6]4- anions (stretching band at 1261 cm(-1)) and
      ruled out the formation of [MnH6]5- complexes. As for the as-milled Mg2Mn, powder
      diffraction analysis showed the formation of MgD2 as the main reaction product. A
      small fraction of a cubic K2PtCl6-type phase (a = 6.526 A) was also observed.
      This was identified as a Mg2FeD6-type compound. It was likely formed as a result
      of Fe impurities originating from the milling media and detected by EDX analysis.
      Infrared spectroscopy confirmed the presence of the [FeD6]4- complex (stretching
      band at 1259 cm(-1)) and showed an additional band at 1313 cm(-1). The likelihood
      of this band arising from Mn-D bonds is discussed. Finally, deuterium desorption
      upon heating, was investigated for all systems by differential scanning
      calorimetry.

PMID- 22455079
TI  - Performance of a full-scale hydrogen-storage tank based on complex hydrides.
AB  - Designing and building a full scale hydrogen storage system revealed several
      engineering challenges and also demonstrated the capabilities of complex
      hydrides. Three kg of hydrogen was stored in a four module system using modified
      sodium alanate as the storage media. Extensive testing of this system
      demonstrated the ability to follow aggressive hydrogen demand schedules that
      simulate actual driving. Extensive use of detailed models greatly improved the
      design and eventual performance of the storage system; the test data permitted
      further refinement of the models.

PMID- 22455080
TI  - Performance of a metal hydride store on the "Ross Barlow" hydrogen powered canal
      boat.
AB  - This project involved the conversion of a British Waterways maintenance craft to
      a canal boat, powered by a combination of a solid-state hydrogen store, Proton
      Exchange Membrane (PEM) fuel cell, lead-acid battery pack and a high-efficiency,
      permanent magnet (NdFeB) electric motor. These replaced the conventional diesel
      engine thus eliminating water, noise, local and general atmospheric pollution.
      The "Protium" project applies modern technologies to a traditional mode of
      transportation. The TiMn2-based metal hydride store exhibited excellent
      performance as an effective means of storing 4 kg of hydrogen with a suitable
      desorption flow rate and temperature adequate for the operation of a 1 kW PEM
      fuel cell in a water-based environment.

PMID- 22455081
TI  - A multidisciplinary combinatorial approach for tuning promising hydrogen storage
      materials towards automotive applications.
AB  - HyStorM is a multidisciplinary hydrogen-storage project aiming to synthesise and
      tune materials hydrogen storage properties for automotive applications. Firstly,
      unique high-throughput combinatorial thin-film technologies are used to screen
      materials' hydrogen storage properties. Then promising thin-film candidate
      compositions are synthesised and examined in the bulk. In this paper, we report
      on our results within the ternary compositions Mg-Ti-B and Ca-Ti-B. Primary
      screening of the Mg-Ti-B ternary identified a high capacity hotspot corresponding
      to Mg0.36Ti0.06B0.58, with 10.6 wt% H2 capacity. Partial reversibility has been
      observed for this material in the thin-film. Bulk Ti-doped Mg(BH4)2 composites
      show rehydrogenation to MgH2 under the conditions used. The synthesised thin-film
      Ca-Ti-B ternary showed only low hydrogen storage capacities. In the bulk, Ti
      doping experiments on Ca(BH4)2 demonstrated reversible storage capacities up to
      5.9 wt% H2. Further characterisation experiments are required to decipher the
      role of the Ti-dopant in these systems in both films and in the bulk.

PMID- 22455082
TI  - Effective hydrogen storage: a strategic chemistry challenge.
AB  - This paper gives an overview of the current status and future potential of
      hydrogen storage from a chemistry perspective and is based on the concluding
      presentation of the Faraday Discussion 151--Hydrogen Storage Materials. The safe,
      effective and economical storage of hydrogen is one of the main scientific and
      technological challenges in the move towards a low-carbon economy. One key sector
      is transportation where future vehicles will most likely be developed around a
      balance of battery-electric and hydrogen fuel-cell electric technologies.
      Although there has been a very significant research effort in solid-state
      hydrogen storage, high-pressure gas storage combined with conventional metal
      hydrides is still seen as the current intermediate-term candidate for car
      manufacturers. Significant issues have arisen in the search for improved solid
      state hydrogen storage materials; for example, facile reversibility has been a
      major challenge for many recently studied complex hydrides while physisorption in
      porous structures is still restricted to cryogenic temperatures. However, many
      systems fulfil the majority of necessary criteria for improved hydrogen storage-
      indeed, the discovery of reversibility in multicomponent hydride systems along
      with recent chemistry breakthroughs in off-board and solvent-assisted
      regeneration suggest that the goal of both improved on-board reversible and off
      board regenerated hydrogen storage systems can be achieved.

PMID- 22455083
TI  - The quest for evidence "Beauty is truth, truth beauty"--that is all ye know on
      earth, and all ye need to know.

PMID- 22455084
TI  - Management of patent foramen ovale in cryptogenic stroke.
AB  - There is currently no consensus on the optimal management of cryptogenic stroke
      in the presence of a patent foramen ovale (PFO). Some physicians do not believe
      in the added value of PFO closure in cryptogenic stroke, whereas, for others,
      cryptogenic stroke represents a situation where PFO closure would be the best
      management. Because of a lack of well-designed randomized trials, guidelines do
      not provide a clear answer. Therefore, the cardiological and neurovascular
      societies in Belgium decided to write an attempt at an expert opinion paper.

PMID- 22455085
TI  - A critical reassessment of murine and rabbit models of atherosclerosis: focus on
      lesion progression and remodelling.
AB  - BACKGROUND: Experimental animal atherosclerosis models are frequently regarded as
      an adequate surrogate for human vascular disease. The external validity of these
      models should be approached critically. OBJECTIVES: The current study provides a
      direct comparison of atherosclerosis progression in four different animal models:
      C57BL/6 apolipoprotein (apo) E(-/-) mice, C57BL/6 low density lipoprotein
      receptor deficient mice (LDLr(-/-) mice), heterozygous LDL receptor deficient
      rabbits (LDLr(+/-) rabbits), and homozygous LDL receptor deficient rabbits (LDLr(
      /-) rabbits). The main objective was to perform a longitudinal analysis of
      arterial remodelling and of the evolution of the medial area during
      atherosclerosis progression. Secondary objectives were to analyse sex differences
      in atherosclerosis progression and to determine intersite correlations. RESULTS:
      Progression of atherosclerosis in all models was accompanied by expansive
      (overcompensatory) remodelling leading not only to the absence of luminal
      narrowing but also to an increase of the absolute lumen size. Atherosclerosis
      progression in mice and rabbits is often accompanied by an increase of the medial
      area. Female mice are more susceptible or equally susceptible to atherosclerosis
      development compared to male mice notwithstanding lower plasma cholesterol
      levels. However, this sex difference was not reiterated in both rabbit models.
      Whereas cholesterol-fed LDLr(-/-) mice show a moderate or strong correlation
      between the extent of advanced atherosclerosis in the aortic root and the
      brachiocephalic artery, no such correlation was observed in apo E(-/-) mice.
      CONCLUSION: The extensive morphometric data in the current study provide a
      framework to critically reassess the potential and limitations of animal models
      of atherosclerosis.

PMID- 22455086
TI  - Spectrum and clinical manifestations of mutations in genes responsible for
      hypertrophic cardiomyopathy.
AB  - INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with
      autosomal dominant inheritance. It is caused by mutations in the genes coding for
      structural and/or regulatory proteins found in the sarcomere of cardiomyocytes. A
      group of genes, including the heavy chain of beta-myosin (MYH7), myosin binding
      protein C (MYBPC3), cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) are
      frequently affected by causal mutations. While exact mutation frequency data has
      been obtained for various populations, no screening has been reported for Central
      European populations. PATIENTS AND METHODS: We performed a complete sequencing of
      MYH7, MYBPC3, TNNI3 and TNNT2 genes in 100 HCM patients. RESULTS: We discovered
      mutations in a total of 40 patients (40%), including 4 patients with double
      mutations. A total of 35 different mutation types were detected, of which 17 were
      novel. The contributions from individual genes were: 24 mutations in MYBPC3
      (54.5%), 14 in MYH7 (31.8%), 4 in TNNI3 (9%) and 2 mutations in TNNT2 (4.5%). We
      have observed a wide variability in disease manifestation across the different
      genes/mutation types. In addition, we have discovered differences in both
      frequency and distribution of mutations of the two most common genes (MYBPC3 and
      MYH7) compared to other populations. CONCLUSION: The most common gene responsible
      for HCM in our study population was MYBPC3, followed by MYH7, TNNI3 and TNNT2.
      Phenotypic heterogeneity, as well as the dissimilarity to other populations,
      prevents effective use of a pre-screening test, which would be directed at the
      most common mutation hotspots, in our population.

PMID- 22455087
TI  - Psychometric properties of the Flemish version of the MacNew heart disease health
      related quality of life questionnaire.
AB  - BACKGROUND: Assessment of health-related quality of life, increasingly being used
      as an outcome measure in cardiovascular disease research studies and clinical
      practice, requires questionnaires with sound psychometric properties. The aim of
      this study was to evaluate the psychometric properties of the Flemish version of
      the MacNew Heart Disease Health-related Quality of Life questionnaire in Flemish
      speaking Belgian patients. METHOD: Between 2002 and 2008, as part of the
      international HeartQol Project, 344 Belgian patients with a diagnosis of angina,
      ischaemic heart failure or myocardial infarction completed the Flemish versions
      of the MacNew, the Short-Form 36 and the Hospital Anxiety and Depression Scale.
      Ceiling and floor effects of the MacNew were analysed. Internal consistency was
      assessed by Cronbach's a and reproducibility (intra-class correlation
      coefficients) was assessed in a subsample of patients over a 2-3 week period with
      repeated tests. Convergent validity (Pearson's correlation between MacNew and
      Short-Form 36 constructs) and discriminant validity ('known-group' approach) were
      tested. RESULTS: The Flemish version of the MacNew appears to be a reliable
      instrument with a high internal consistency, demonstrating strong discriminative
      validity and satisfactory construct validity. The results of factor analysis are
      similar to the factor structure of the original MacNew explaining 59.8% of the
      total variance. CONCLUSION: The Flemish version of the MacNew demonstrates good
      psychometric properties. It can be recommended as a specific instrument for
      assessing and evaluating health-related quality of life in Flemish-speaking
      patients in each of the three major ischaemic heart disease diagnoses: angina,
      ischaemic heart failure and myocardial infarction. However, responsiveness to
      change could not be tested in this cross-sectional study and should be further
      investigated in a larger sample of patients following an intervention likely to
      induce a change in health-related quality of life.

PMID- 22455088
TI  - Impact of social characteristics on the treatment of patients with ischaemic
      events and patent foramen ovale.
AB  - OBJECTIVE: Percutaneous closure of a patent foramen ovale (PFO) is a technically
      simple and safe procedure. PFO is a common finding present in up to one third of
      the population. Although several conditions such as stroke, migraine, and sleep
      apnoea have been associated with a PFO, as underlined by observational studies,
      no causal relationship has been documented so far. As this setting may
      potentially leave more space for the involved physicians for the choice of
      treatment, we hypothesized that social characteristics of the patient with a PFO
      might play a role. METHODS: We retrospectively analysed the data of 153 patients
      with a cerebrovascular and/or peripheral ischaemic event with the diagnosis of a
      PFO as documented in echocardiography from 2000 until 2005 at the University
      Hospital in Zurich, Switzerland. RESULTS: Forty-four patients (= 23%) underwent
      catheter-based PFO closure. There was no significant difference with respect to
      age (<40 years: P = 0.094, ns; 40-59 years: P = 0.923, ns; > or =60 years: P=
      0.234, ns), gender (P = 0.356, ns) and insurance status (<40 years: P= 0.15, ns;
      40-59 years: P= 0.37, ns; 60 years: P = 0.26, ns) between those who underwent
      percutaneous PFO closure and those who did not. CONCLUSION: We conclude from this
      single-centre experience that social characteristics of patients only have a
      marginal impact on the indication of percutaneous closure of a PFO, if at all.

PMID- 22455089
TI  - In adults with atrial switch operation for transposition of the great arteries
      low physical activity relates to reduced exercise capacity and decreased
      perceived physical functioning.
AB  - OBJECTIVE: Patients with Mustard/Senning repair for transposition of the great
      arteries (d-TGA) have an impaired exercise capacity, but information about
      physical activity levels is scarce. The aim of the study was to come to a better
      understanding of the interrelationships between determinants of exercise
      capacity, physical activity and self-perceived health status. METHODS AND
      RESULTS: We studied 39 d-TGA patients who underwent echocardiography and exercise
      testing, and who completed questionnaires about physical activity and perceived
      health status. All results were compared with normal values. Stepwise multiple
      regression analysis was used to assess the determinants of peak V02% and exercise
      duration. Peak VO2 averaged 64 +/- 14.1% of the predicted normal values, which is
      significantly lower than expected (P < 0.0001). Physical activity measures as
      well as perceived general health were significantly lower compared to a reference
      population (P < 0.05). Peak heart rate and peak oxygen pulse explained together
      90% of the variability in exercise duration (model F = 162.72; P < 0.0001). Type
      of surgery, total energy expenditure and right ventricular contractility were
      independent predictors of peak VO2% explaining 43% of the variability (model F =
      8.75; P = 0.0002). CONCLUSIONS: Impaired peak exercise performance in d-TGA
      patients results mainly from the inability to increase stroke volume and heart
      rate at higher exercise intensities. Senning repair and a well-preserved right
      ventricular function are related to a better peak V02%. Furthermore, an active
      lifestyle has a positive effect on exercise capacity and perceived physical
      functioning. Therefore it might be indicated to encourage d-TGA patients to adopt
      a more physically active lifestyle.

PMID- 22455090
TI  - Valvular heart disease: plasma B-type natriuretic peptide levels in patients with
      pure rheumatic mitral stenosis.
AB  - OBJECTIVE: Our study is designed to evaluate the plasma BNP levels in patients
      with pure MS and its possible correlation with clinical and echocardiographic
      parameters of the disease. METHODS AND RESULTS: The study included 29 patients
      (27 women, 2 men, mean age 43.4 +/- 11.8 y) with pure mitral valve stenosis in
      sinus rhythm and 24 age- and gender-matched healthy voluteers (17 women, 7 men,
      mean age 42 +/- 13 y). Plasma BNP levels were significantly higher in the mitral
      stenosis group compared to controls (91.1 +/- 69.6 pg/ml vs. 14.4 +/- 9.2 pg/ml,
      P < 0.0001). In univariate analysis, plasma BNP levels correlated positively with
      left ventricular end-systolic diameter (r = 0.439, P = 0.041), left atrial
      diameter (r = 0.772, P < 0.001), peak diastolic transmitral gradient (r = 0.621,
      P = 0.003), mean diastolic transmitral gradient (r = 0.751, P < 0.001), peak
      systolic pulmonary artery pressure (r = 0.467, P = 0.044), functional capacity (r
      = 0.819, P < 0.001) and negatively with left ventricular ejection fraction (r = 
      0.482, P = 0.020) and planimetric mitral valve area (r = -0.494, P = 0.006). No
      significant correlation existed between age, end-diastolic diameter and right
      ventricular diameter (r = 0.185, P = 0.337; r = 0.227, P = 0.309; r = 0.319, P =
      0.092; respectively). A receiver operating characteristic (ROC) curve identified
      a BNP value of 32 pg/ml as the best cut-off for the identification of patients
      with mitral stenosis with a positive predictive value of 100% and a negative
      predictive value of 75%. CONCLUSIONS: In this study we found elevated plasma BNP
      levels in patients with pure MS in sinus rhythm. Plasma BNP levels correlated
      with disease severity and this can have potential clinical implications, for
      example in patients undergoing percutaneous balloon mitral valvuloplasty or in
      patients with poor echocardiographic windows.

PMID- 22455091
TI  - Prevalence of atrial fibrillation in Greece: the Arcadia Rural Study on Atrial
      Fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) is a major factor for stroke and stroke
      associated mortality, and its incidence is increasing during the last decades.
      There are only scarce data about its prevalence in Greece. We designed an
      epidemiological cross-sectional study to estimate the prevalence of AF in Greece
      and evaluate the adequacy of anticoagulant treatment in AF patients. SUBJECTS AND
      METHODS: The Arcadia Rural Study on Atrial Fibrillation (ARSAF) was conducted
      between 2002-2003 in five rural villages of the Arcadia province (Greece) with a
      permanent population of 1312 individuals. Patients had a thorough medical
      examination and electrocardiogram, and information was collected about their
      medical history and comorbidities. CHADS2 score was used to determine stroke risk
      for participants with AF. RESULTS: 1155 subjects (88% of the entire population)
      participated in the study. The overall prevalence of AF was 3.9% showing an
      increasing trend with increasing age ranging from 0.4% in patients <55 years to
      10.7% in patients > 84 years. Among patients with AF, 14 (32%) had paroxysmal AF.
      The presence of AF was associated with increasing age (OR: 1.67 for every 10
      years increase, 95% CI: 1.26-2.15), hypertension (OR: 2.12, 95% CI: 1.02-4.14),
      heart failure (OR: 11.85, 95% CI: 4.92-28.56) and prior cerebrovascular disease
      (OR: 4.17, 95% CI: 1.44-12.06). Among these subjects with AF, 12 (26.6%) were
      considered as low-risk (CHADS2 = 0), 18 (40.0%) as intermediate-risk (CHADS2 =
      1), and 15 (33.3%) as high-risk (CHADS2 > 1) patients for stroke. 25 (55.5%)
      patients with AF did not receive appropriate antithrombotic treatment.
      CONCLUSION: The prevalence of AF in Greece is similar to other countries and
      increases with increasing age.

PMID- 22455092
TI  - Association of type 2 diabetes mellitus with coronary atherosclerotic plaque
      burden and morphology measured by multidetector computed tomography coronary
      angiography.
AB  - AIMS: Diabetes mellitus (DM) is strongly associated with increased risk of
      coronary artery disease (CAD). The aim of this study was to determine differences
      in presence, extent and morphology of coronary atherosclerotic plaques (CAP)
      detected by multidetector computed tomography (MDCT) between symptomatic patients
      with and without diabetes. METHODS: The CAPs (calcified, non-calcified, mixed)
      were compared between patients with/without diabetes (104/257 DM; mean age 58.6
      +/- 11 y; 46.3% male) who underwent dual-source 64-slice MDCT for evaluation of
      CAD. Severity, extent and morphology of CAPs were determined per each segment.
      RESULTS: Critical coronary stenosis was higher in patients with diabetes (33.7%
      vs. 19.6%) after adjustment for all risk factors (P = 0.022). Patients with DM
      had a higher prevalence and extent of CAP compared to non-diabetic subjects
      (87.5% vs. 43.8%, 4.8 +/- 3.5 vs. 1.9 +/- 2.7, respectively; P < 0.001).
      Noncalcified and mixed CAP were more prevalent in patients with diabetes as
      compared to those without diabetes (2.61 +/- 2.63 vs. 0.86 +/- 1.69, 0.81 +/- 1.6
      vs. 0.35 +/- 0.96, respectively, P < 0.001). Patients with DM tended to have
      higher prevalence of significant 1-, 2- and 3-vessel disease (P = 0.006).
      CONCLUSIONS: Among individuals referred for the evaluation of CAD, those with DM
      had a higher risk of coronary stenosis and overall increased CAP burden
      independent from other cardiovascular risk factors shown by MDCT. Further studies
      are needed to evaluate the prognostic value of different plaque compositions
      observed in patients with diabetes.

PMID- 22455093
TI  - Effect of fat pad ablation on the spatial and temporal stability of complex
      fractionated atrial electrogram in acetylcholine-induced atrial fibrillation.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of selective
      fat pad ablation on the spatial and temporal stability of the complex
      fractionated atrial electrogram (CFAE) in acetylcholine (ACh)-induced atrial
      fibrillation (AF). METHODS AND RESULTS: ACh was applied to fat pads in 10 dogs.
      Effective refractory periods (ERPs) at 5 different sites, AF inducibility and AF
      duration were obtained before and after fat pad ablation. During the first two
      induced AFs, the number of sites with continuous CFAEs and the duration of
      continuous CFAEs at every site were measured before and after fat pad ablation.
      The average ERP was shortened by ACh application (138 14 vs 100 15 ms, P < 0.001)
      and increased after fat pad ablation (100 +/- 15 vs. 115 +/- 14 ms, P < 0.001).
      AF inducibility (76 +/- 9% vs. 4 +/- 6%, P < 0.001) and AF duration (56 +/- 11
      vs. 187 +/- 56 s, P = 0.01) increased after ACh application compared to baseline;
      while fat pad ablation reduced AF inducibility (76% +/- 9% vs. 54% +/- 6%, P <
      0.001) and AF duration (187 +/- 56 vs. 144% +/- 35 s, P = 0.015). The percentage
      of sites with continuous CFAE decreased after fat pad ablation compared with that
      before fat pad ablation (24% vs. 82%, P < 0.001). On average, fat pad ablation
      reduced the duration of continuous CFAEs (188 +/- 63 vs. 139 +/- 31 s, P <
      0.001). CONCLUSION: Selective fat pad ablation can affect the spatial and
      temporal stability of CFAEs in ACh-induced atrial fibrillation in dogs.

PMID- 22455094
TI  - Cardioprotective effects of zofenopril, enalapril and valsartan against
      ischaemia/reperfusion injury as well as doxorubicin cardiotoxicity.
AB  - OBJECTIVE: The aim of this study is to compare possible protective effects of
      zofenopril, enalapril and valsartan against both ischaemia/reperfusion injury as
      well as acute doxorubicin cardiotoxicity. All three agents have never been
      compared in this setting before. METHODS AND RESULTS: Sixty-four male rats were
      divided into eight groups by computer-generated random numbers and each group
      included 8 rats. Groups 1, 2, 3 and 4, respectively, received 0.5 ml distilled
      water, 15 mg/kg/day zofenopril, 2 mg/kg/day enalapril, and 30 mg/kg/day valsartan
      intragastrically for 7 days. Groups 5, 6, 7, and 8 underwent the same procedures
      as groups 1, 2, 3 and 4. On the 7th day, groups 1-4 and groups 5-8, respectively,
      were injected with serum saline or 20 mg/kg doxorubicin intraperitoneally. On the
      9th day, isolated rat hearts were perfused in the Langendorff perfusion system.
      At the end of each Langendorff experiment, the rat hearts were kept for
      histological analysis. Left ventricular systolic pressures were negatively
      affected by doxorubicin with ischaemia (group 5 initially: 61.4 +/- 13.6 mmHg-
      post-ischaemic (PI): 20.7 +/- 17.5 mmHg (P = 0.0002), group 6 initially: 63 +/-
      18.2 mmHg--PI: 24.2 +/- 24.3 mmHg (P = 0.0135), group 7:82 +/- 26 mmHg--PI: 14.3
      +/- 12.1 mmHg (P < 0.0001), group 8:73.1 +/- 27.8 mmHg--PI: 20.4 +/- 27.3 mmHg (P
      < 0.0001). The lowest troponin I levels (group 2: 0.3 +/- 0.2 ng/ml, group 6:0.2
      +/- 0.1 ng/ml (P = 0.003) versus the groups' baseline value) were recorded in the
      groups of zofenopril in the coronary perfusate during post-ischaemic period.
      Light microscopic evaluation revealed marked cardiac damage with doxorubicin,
      since zofenopril treatment prevented a doxorubicin induced increase in the
      histopathological scores. CONCLUSIONS: In respect of our results zofenopril could
      be considered more effective than enalapril and valsartan in protecting against
      both ischaemia/reperfusion injury as well as doxorubicin induced-cardiotoxicity.

PMID- 22455095
TI  - Atrial flutter in normal heart could be first manifestation of Brugada syndrome.
AB  - Brugada syndrome is one of the important causes of sudden cardiac death in young
      adults. The condition is associated with typical ECG changes in anteroseptal
      leads V1 and V2 that can be unmasked by various medications, electrolyte
      disturbances, and even by fever in susceptible individuals. We here report the
      case of a 22-year-old female admitted to the emergency room with a typical atrial
      flutter who developed Brugada-like ECG changes after conversion to sinus rhythm
      following flecainide infusion with subsequent degeneration in ventricular
      fibrillation. The patient converted to sinus rhythm after external DC shock
      intervention. At hospital admission she reported no family history of sudden
      cardiac death, nor syncope or paroxysmal palpitations. The cardiac
      echocardiographical exam revealed no structural abnormalities and a normal
      ejection fraction. This case highlights once more the importance of recognising
      supraventricular arrhythmias or other rhythm disturbances in young healthy
      patients as the revealing sign of other underlying pathologies.

PMID- 22455096
TI  - Acute heart failure due to fulminant myocardial infiltration by a diffuse large B
      cell lymphoma.
AB  - Secondary cardiac lymphoma is commonly recognised as one of the most frequent
      metastatic malignancies involving the heart, after lung and breast carcinomas.
      Most primary and secondary cardiac lymphoma are non-Hodgkin lymphomas.The
      pericardium is the most frequently involved cardiac structure. However, the
      myocardium and the endocardium can also be affected. The patient presented in
      this case report had a secondary cardiac diffuse large B cell lymphoma. He
      presented initially with dyspnoea due to cardiac tamponade. He died one month
      after pericardial fenestration as a result of acute left and right heart failure
      due to diffuse lymphomatous infiltrations.This cardiac infiltration progressed so
      quickly that histological diagnosis could not be obtained before death. Autopsy
      revealed massive infiltration of the heart, the thyroid, abdominal lymph nodes,
      the left kidney, the pancreas and the right testis.

PMID- 22455097
TI  - The masquerading act of ST elevation.
AB  - Acute myocardial infarction resulting from an occlusive thrombus is recognized on
      an electrocardiogram by ST-segment elevation. The earlier the reperfusion, the
      greater the benefit, and the time to treatment is now considered to indicate the
      quality of care. In the current era when percutaneous interventions are carried
      out so readily, it is important to remember that acute infarction is not the only
      cause of ST-segment elevation. We hereby report a case of Prinzmetal's angina
      which mimics presentation of STEMI in many respects.

PMID- 22455098
TI  - Unusual abnormal pulmonary venous return.
AB  - We describe a case of a middle-aged woman, known with situs inversus totalis. She
      was suffering from progressive dyspnoea. With different imaging techniques we
      came to the correct diagnosis, a partial abnormal pulmonary venous return, which
      was surgically confirmed. Although the structure was complex, the treatment was
      simple.

PMID- 22455099
TI  - College student perceptions on campus alcohol policies and consumption patterns.
AB  - Environmental strategies for colleges and universities to reduce alcohol
      consumption among their students include the development and enforcement of
      campus alcohol policies. This study examines students' knowledge and attitudes
      toward campus alcohol policies and how they relate to alcohol consumption and
      alcohol social norms. A sample of 422 freshman students was surveyed during their
      first month at a 4-year public college. Findings indicated that the majority of
      students (89%) were aware of campus policies, yet of those who were aware, less
      than half (44%) were accepting of these campus rules and regulations. In
      addition, the majority (79%) of students drank at social events, despite this
      behavior being in direct violation of campus alcohol policies. However, those who
      supported campus rules consumed significantly less alcohol at social events than
      those who opposed or had no opinion of the rules. Also, those who supported the
      rules perceived that their peers and students in general consumed significantly
      less alcohol at social events than those who were opposed or had no opinion. This
      outcome supports the premise established by several theories of behavior change
      including the theory of planned behavior, which state that behavior is influenced
      less by knowledge than by attitude and intention.

PMID- 22455100
TI  - Academic demands are associated with reduced alcohol consumption by college
      students: evidence from a daily analysis.
AB  - There is little empirical evidence linking academic demands or rigor to alcohol
      consumption by college students. In a 3-week daily study of full-time college
      students at a public, residential campus in the United States, both current day
      and next day's academic demands were negatively related to alcohol consumption,
      and these relationships were mediated by daily academic effort. Academic demands
      on the previous day were not related to alcohol consumption, indicating that
      students do not engage in compensatory or celebratory drinking when demands end.
      The results suggest that enhancing academic expectations and rigor may be an
      appropriate intervention target to reduce student drinking.

PMID- 22455101
TI  - Does marijuana use lead to aggression and violent behavior?
AB  - Marijuana use and violent behavior are causing widespread public concern. This
      article reviews theory and research on the relation between marijuana use and
      aggressive/violent behavior. It is evident from the inconsistent findings in the
      literature that the exact nature of the relation remains unclear. This article
      identifies several possible reasons for these contradictory findings and provides
      suggestions for future research. In particular, more research is needed on the
      different subtypes of aggressive behavior. Further research is also needed to
      elucidate the associations between gender, marijuana use, and violent behavior.
      Likewise, an important task for future research is to continue to tease apart the
      complex relations between gang involvement, marijuana use, and violent behavior.
      Longitudinal studies also warrant further investigation. Moreover, future
      research should control for several potentially confounding variables.

PMID- 22455102
TI  - The effects of drinking status and believability of ads featured in a social
      norms campaign on college students' estimation and accuracy of other students'
      celebratory drinking.
AB  - This study examined estimation and accuracy of normative perceptions for students
      during one celebratory drinking occasion. Students who drank on St. Patrick's Day
      overestimated the percentage of others who also drank, whereas the students who
      did not drink on St. Patrick's Day underestimated the percentage of others who
      also did not drink. The students' drinking behaviors on St. Patrick's Day did not
      substantially differentiate their accuracy scores. However, of the students who
      drank on St. Patrick's Day, those who did not believe the ads showed stronger
      overestimation of others who drank than did those who believed the ads.

PMID- 22455104
TI  - An empirical assessment of the Above the Influence advertising campaign.
AB  - This study evaluated the efficacy of Above the Influence (ATI), a national media
      based health persuasion campaign to deter youth drug use. The campaign uses
      public service anti-drug prevention messages and targets youth between the ages
      of 14 and 16, a period of heightened susceptibility to peer influences. The
      evaluation utilized mall intercepts from geographically dispersed regions of the
      country. Theoretical impetus for the campaign combines elements of the theory of
      reasoned action (TRA), persuasion theory, and the health belief model. A series
      of structural equation models were tested with four randomly drawn cross
      validation samples (N = 3,000). Findings suggest that awareness of ATI is
      associated with greater anti-drug beliefs, fewer drug use intentions, and less
      marijuana use. Congruent with the TRA, changes in beliefs and intentions are
      intermediate steps linking campaign awareness with behavior. This study provides
      further evidence of positive campaign effects and may strengthen reliance on mass
      media health persuasion campaigns as a useful adjunct to other programs targeting
      youth.

PMID- 22455103
TI  - Efficacy of a web-based, tailored, alcohol prevention/intervention program for
      college students: 3-month follow-up.
AB  - This study presents the results of an efficacy evaluation of a web-based brief
      motivational alcohol prevention/intervention program called Michigan Prevention
      and Alcohol Safety for Students (M-PASS). Four on-line sessions providing
      individually-tailored feedback were delivered to first-year college students over
      9 weeks. Non- and low-risk drinking participants received risk prevention, while
      high-risk drinking participants received a risk-reduction intervention. Both
      intervention and control groups were surveyed at baseline and at a 3-month follow
      up. Analysis showed positive effects for both men and women on stage of change,
      drinking behavior, drinking motivation and attitudes, and use of risk-reduction
      strategies. These results provided evidence of efficacy and found that M-PASS had
      both intervention and prevention effects, making it unique among currently
      developed brief alcohol interventions for college students.

PMID- 22455105
TI  - Through the touch of god: child death and spiritual sustenance in a Hutterian
      colony.
AB  - Nestled in more than 5,000 acres of farmland in rural South Dakota, one Hutterian
      colony flourishes with more than 23 families and a population of 115 people. Very
      little is known about the ways in which Hutterites experience traumatic infant
      and child death on the colony. No research studies to date have explored this
      topic. This is an ethnographic study that utilized extended observations of the
      group and both individual and group interviewing in order to create a cultural
      portrait specifically focusing on Hutterites experiencing traumatic child death.
      Observations were organized into five thematic categories: 1) details of the
      actual death experience; 2) emotional and physical reactions to the loss; 3)
      familial and communal response; 4) coping and rituals; and 5) spirituality. The
      role of communal mourning, ritualization, and spirituality in creating a healing
      milieu for bereaved families is discussed.

PMID- 22455106
TI  - Researching "good death" in a Hong Kong palliative care program: a clinical data
      mining study.
AB  - This study operationalizes and assesses the percentage of "good deaths" achieved
      among Chinese cancer patients in a palliative care program, the profile of these
      patients, the relationship between patients with a good death and psychosocial
      factors, and the differences in background factors, and physical and psychosocial
      conditions between patients who experienced a good death and those who did not.
      Clinical data mining was the research method used. Records of deceased cancer
      patients between 2003 and 2005 in a palliative care unit were the sole data
      source. Good death was operationally defined as the patient's record indicating
      no pain (physical) or anxiety (psychological), and having open and honest
      communication with family (social) in the final assessment by the Support Team
      Assessment Schedule (STAS) just before death. Using these criteria, about one
      fifth of patients (21.5%; 137 out of 638) experienced a good death. Those with a
      good death were significantly older and were in palliative care longer. Their
      records also indicated lower levels of constipation, insomnia, oral discomfort,
      and family anxiety at their first and at their final STAS assessments. Good death
      was positively associated with recorded indicators of fullness in life,
      caregivers' acceptance and support, and negatively with reported feelings of
      upset about changes in the course of their illness. The results heighten
      awareness among social workers and other healthcare professionals about the value
      of good death in patients in palliative care. This empirically-based awareness
      can foster professionals' ability to set intervention objectives to help patients
      in palliative care achieve this universally accepted goal.

PMID- 22455107
TI  - "You are weeping for that which has been your delight": to experience and recover
      from grief.
AB  - To explore how people experience grief and what factors are perceived as
      facilitating successful grief work, a survey was distributed to people who had
      completed a grief recovery course. The results showed that emotions, cognitions,
      physical expressions, and behaviors all characterize grief, but that emotions are
      the most central component. The course brought relief and was regarded most
      favorably by those having at least 1 year between the grief trigger event and
      participation in the course. Writing a letter in which course participants
      express their feelings to the loss object was perceived as the most successful
      aspect of the course. The letter might help with grief recovery by bringing
      aspects that have not been dealt with into conscious awareness.

PMID- 22455108
TI  - College student bereavement experience in a Christian university.
AB  - As part of the National College Grief Study, college student bereavement
      experience was examined specifically in a Christian university climate. Sex, year
      in school, and closeness to the deceased were measured in terms of academic and
      mental health outcomes and resources utilized. Females reported more mental
      health problems when close to the deceased, and seniors were less likely than
      first year students to utilize personal support resources of family and religion.
      During close losses, students experienced more mental health problems and
      negative social outcomes, but they did not access more resources. Recommendations
      for university personnel and suggestions for further research are given.

PMID- 22455109
TI  - Samuel Hieron's "Worldling": a funeral sermon, 1618 and the controversy over
      eulogies.
AB  - After the Reformation, English clergymen debated the efficacy of funeral
      eulogies. Some believed they flattered the deceased and might be seen as prayers
      for the dead. Because the bereaved wanted to hear about the goodness of their
      beloved, most preachers gave eulogies, some in a generalized form for Godly
      imitation, not expressing the deceased's individuality. Samuel Hieron, a Puritan
      preacher, refused to give eulogies. In two that were printed, he used Biblical
      texts lauding the lives of Paul and Dorcas, making it possible for the grief
      stricken to believe he was comparing the deceased to them. In the third, he used
      a text about a Worldling, angering the deceased's daughters, who believed he
      claimed their father had died a wicked man. Hieron prepared the sermon for
      publication to deny their charges but died before it appeared. His experience
      indicates parishioners expected to participate in decisions about how funeral
      services were conducted.

PMID- 22455110
TI  - Mystery stick: a dirty needle turns one patient into two.

PMID- 22455111
TI  - Kindescending: do some of us inflict, rather than offer, our help?

PMID- 22455112
TI  - 40 years & counting--part I: show me the money.

PMID- 22455113
TI  - Evolving EMS: Q&A with Sabina Braithwaite, MD, MPH.

PMID- 22455114
TI  - Gentle drug math.

PMID- 22455115
TI  - Troubled mind: the lowdown on increased ICP.

PMID- 22455116
TI  - Sprinting to service: when it comes to vehicles, Balentine Ambulance Service has
      seen great results with the smaller sprinter platform.

PMID- 22455117
TI  - 'Home Days' can showcase EMS industry to lawmakers: EMS providers are their own
      best voice in Washington.

PMID- 22455118
TI  - Solar support: in Richmond, sun-powered trucks save big bucks.

PMID- 22455119
TI  - Seeing is believing: our downtime isn't time off, but who knows?

PMID- 22455120
TI  - [Study on the effect and mechanism of hypoxia on the histological structure of
      rat's lung].
AB  - OBJECTIVE; To observe the effect of intermittent normobaric hypoxia on the
      expression of transforming growth factor betal (TGF-beta1), Smad4, collagen I
      (Col I), tumor necrosis factor alpha (TNF-alpha) and on the changes in the
      histological structure of SPF SD Rat's lung. METHODS: Rats were placed in normal
      environment or intermittent normobaric hypoxia (101 kPa, 10% O2, 8 h every day)
      respectively. At the 3rd, 7th, 14th, 21st day, 5 rats from each group were killed
      and hematoxylin and eosin stain (HE stain) was applied to observe the
      pathological change in the lung of rats, immunohistochemical staining was used to
      detect the protein level of TGF-beta1, Col I. RT-PCR was performed to detect the
      mRNA levels of TGF-beta1 and Col I. Western blot to detect the expression of
      Smad4. Besides, the TNF-alpha in the bronchoalveolar lavage (BALF) were
      determined by ELISA. RESULTS: Results of HE stain demonstrated that the mild
      edema and inflammatory cell infiltration appeared in the lung tissue at the 3rd
      day, and gradually aggravated inflammation were observed as the treated time
      extended; meanwhile the interalveolar septum become thicker and thicker as the
      time of exposing to normobaric hypoxia increased. Compared with the normoxia
      group, not only the protein expression of TGF-beta1, Smad4 and Col I, but also
      the mRNA expression of TGF-beta1 and Col I were elevated (P < 0.01) in normobaric
      hypoxia group as the treatment time extended. Besides, a positive correlation (r
      = 0.944, P < 0.01) between the protein level of TGF-beta1 and Smad4 was observed
      and an up-regulated TNF-alpha in the BALF was also noticed. CONCLUSION:
      Normobaric hypoxia could cause pulmonary edema and inflammation by up-regulating
      expression of TNF-alpha, activating the TGF-beta1/Smads Signaling Pathway, and
      increasing the synthesization of Col I, the deposition of extracellular matrix as
      well as the interalveolar septum thickness.

PMID- 22455121
TI  - [Numb expression in colon cancer and its significance].
AB  - OBJECTIVE: To investigate the expression pattern of Numb, a membrane associated
      protein, in colon cancer and its biological significance. METHODS: Routine
      immunohistochemistry staining was used to detect the expression of Numb in tissue
      microarray with 60 cases of colon cancer tissue and 20 normal colon tissue. The
      clinical data was analyzed. The expression of Numb in SW480, SW620 cell lines
      were evaluated by immunostaining and Western blot. RESULTS: The positive
      expression rate of Numb in cytoplasm decreased in poorly differentiated tumor
      tissue than normal tissue and well and moderately differentiated colon cancer (P
      < 0.05), and the expression intensity was correlated with the differentiation
      state of cancer tissue. Westen blot results showed that colon cancer cell line
      SW480, compared with SW620 has a higher protein expression (P < 0.05). A punctate
      distribution of Numb in cytoplasm in colon cancer cell under confocal
      immunofluorescence was observed. A increased expression density in SW480 cell
      line was noticed when compared with that in SW620 cell line (P < 0.05).
      CONCLUSION: Numb may has an important regulation in the process of tumor
      progression and play a protective role against tumor development.

PMID- 22455122
TI  - [Effects of a low-fat and high-carbohydrate diet on the physiological and
      biochemical indices in healthy youth with different body mass index].
AB  - OBJECTIVE: To investigate the effects of a low-fat and high-carbohydrate (LF-HC)
      diet on the physiological and biochemical indexes in healthy youth with different
      body mass index (BMI). METHODS: Seven overweight participants [BMI=(27.82 +/-
      1.64) kg/m2] and 49 age-matched controls [BMI = (20.06 +/- 2.41) kg/ m2] were
      given a washout diet for 7 d, followed by a LF-HC diet for 6 d. The washout diet
      contained 31.1% fat and 54.1% carbohydrate, and the LF-HC diet contained 14.8%
      fat and 70.1% carbohydrate of total energy. Anthropometric measurements were
      conducted on the mornings of the first, eighth and fourteenth days. Serum samples
      were prepared from twelve-hour fasting venous blood. Biochemical indexes
      including lipids; glucose and insulin were measured with routine methods. The
      homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.
      RESULTS: At baseline, the control group had lower levels of body mass (P =
      0.000), BMI (P = 0.000), waist-hip ratio (P = 0.000), systolic blood pressure (P
      = 0.001), diagnostic blood pressure (P = 0.016) and triglycerides (P = 0.006),
      and a higher level of HDL cholesterol (P = 0.005) than the overweight group. When
      compared with those before the ILF-HC diet, total cholesterol (P < 0.05) and LDL
      cholesterol (P < 0.05) decreased, and insulin (P < 0.05) and HOMA-IR (P < 0.05)
      increased in both the control group and the overweight group after the LF-HC
      diet. Increased triglycerides (P = 0.000) were observed only in the control
      subjects, and HDL cholesterol (P = 0.018) increased only in the overweight
      subjects after the LF-HC diet. CONCLUSION: The responses of serum TG and HDL-C to
      the LF-HC diet are related to BMI in healthy youth.

PMID- 22455123
TI  - [Isolation and biological characterization of human amniotic fluid-derived stem
      cells].
AB  - OBJECTIVE: To establish in vitro culture procedure for human amniotic fluid
      derived CD117 positive stem cells, and to identify the characteristics of CD117
      positive stem cells. METHODS: 86 amniotic fluid samples (10 mL of each) were
      obtained by second-trimester amniocentesis. Isolation of amniotic fluid-derived
      stem cells expressing CD117 antigen was performed via magnetic cell sorting using
      the CD117 MicroBead Kit. The karyotype of CD117 positive stem cells was analysed
      through repeated freezing. Adipogenic differentiation of these CD117 positive
      stem cells was displayed by Oil Red O staining. Osteogeneic differentiation of
      these CD117 positive stem cells was confirmed by Alizarin Red staining. RESULTS:
      The CD117 positive stem cells were successfully isolated and cultured from 61
      samples, with all showing normal karyotype. Product analysis of specific staining
      confirmed that under specific culture mediums, these cells could be successfully
      induced to differentiate into adipocytes and osteocytes. CONCLUSION: Based on
      this study, we estimate that isolating CD117 positive stem cells from second
      trimester amniotic fluid obtained by amniocentesis has a success rate of 70.93%.
      These cells maintain morphological and genetic stability in vitro. Human amniotic
      fluid-derived CD117 positive stem cells have the ability to differentiate in
      vitro into adipocytes and osteocytes under specific culture mediums and may be
      applied in cell transplantation and regenerative medicine.

PMID- 22455124
TI  - [Expression of thrombospondin-1 in the lung of hypoxic pulmonary hypertension
      rats].
AB  - OBJECTIVE: To investigate the expression of thrombospondin-1(TSP-1) in the lung
      of hypoxia-induced pulmonary hypertension rats. METHODS: Thirty male Wistar rats
      were divided into two groups, pulmonary hypertension group and control group. The
      mice in experimental group were exposed to isobaric hypoxia for 3 weeks, and
      those in control group were exposed to air. The pulmonary artery pressure was
      measured by right cardiac catheterization. The expression of TSP-1 and TGF-beta1
      in the lungs of rats were measured by immunohistochemical staining. The
      histological sections of the lungs were examined using a computerized image
      analyzer. RESULTS: After the induction of hypoxia for 3 weeks, the rats had
      pulmonary artery pressure increased with the thickening of the wall and the
      narrowing of the lumen of pulmonary arterioles. In the experimental group, the
      mean pulmonary artery pressure (mPAP) was (2.86 +/- 0.39) kPa, the index of right
      ventricular hypertrophy RV/(LV+S) was (43.53 +/- 3.38)%, the ratio of vascular
      wall thickness/vascular external diameter (WA%) was (55.09 +/- 12.38)%, and the
      ratio of vascular wall area/total vascular area (WT%) was (35.24 +/- 11.2)%,
      which all were significantly increased in comparison with those of control group
      [mPAP (1.35 +/- 0.28) kPa, RV/(LV+S) (23.68 +/- 3.48)%, WT% (23.63 +/- 9.74)%,
      WA% (41.62 +/- 12.83)%, respectively. P < 0.05). The positive staining of TSP-1
      (1.32 +/- 0.04 vs. 0.96 +/- 0.03) and TGF-beta1 (1.38 +/- 0.05 vs. 1.04 +/- 0.04)
      in the wall of pulmonary arteriole of the rats exposed to hypoxia were
      significantly stronger than those of control rats (P < 0.01). CONCLUSION: The
      expression of TSP-1 appears to be increased in hypoxic pulmonary hypertension
      rats, which may contribute to the pathogenesis of hypoxic pulmonary vascular
      remodeling.

PMID- 22455125
TI  - [Reconstitution of humoral immunity by the transplantation of human umbilical
      cord blood CD34+ cells into NOD/ SCID mice].
AB  - OBJECTIVE: To investigate the immune reconstitution by the transplantation of
      human umbilical cord blood CD34+ cells in the NOD/SCID mouse. METHODS:
      Mononuclear cells (MNC) were isolated from human fresh cord blood and CD34+
      hematopoietic stem cells were selected by magnetic activated cell sorting method.
      The selected cells were transplanted via tail vein injection into 16 NOD/SCID
      mice after sublethal whole-body irradiation. Four mice were sacrificed
      respectively at 4th, 6th, 8th and 10th week after the transplantation, the
      harvested spleen and peripheral blood cells were used to cell phenotype analysis
      and humoral immune analysis, respectively. There were 14 mice in another two
      groups, 7 mice did not receive the transplantation after irradiation, 7 were used
      as blank control (no irradiation, no transplantation). RESULTS: The mice without
      transplantation all died within 2 weeks after irradiation. The survival rate of
      the mice with transplantation was 37.5% at 6th week after the irradiation, while
      the survival rate of blank control was 100%. At 4th, 6th, 8th and 10th week, the
      percentage of human CD45+ cells in transplantation group were 4.7 +/- 1.23, 9.22
      +/- 2.07, 12.34 +/- 2.38, 8.14 +/- 2.36, respectively, and the percentage of
      CD19+ B lymphocytes were 1.07 +/- 0.50, 2.17 +/- 0.95, 3.34 +/- 0.90, 1.67 +/-
      0.90, respectively. 10 weeks after the transplantation, human CD19+ B lymphocytes
      distribution were found in the transplanted mice spleen. CONCLUSION: The human
      mouse chimeric immune model can be built in irradiated NOD/ SCID mice by the
      transplantation of human cord blood CD34+ cells. CD34+ cell differentiation
      declined with time, which might be due to the lack of appropriate cytokines.

PMID- 22455126
TI  - [Investigate the effects of compound radix notoginseng on renal interstitial
      fibrosis and kidney-targeting treatment].
AB  - OBJECTIVE: Investigate the effects of compound Radix Notoginseng on renal
      interstitial fibrosis and kidney-targeting treatment. METHODS: 100 healthy
      Sprague-Dawley rats were randomly divided into 5 groups: Unilateral ureteral
      obstruction (UUO) group, sham-operation (SOR) group, Radix Notoginseng (RN)
      group, compound Radix Notoginseng (CRN) group and Losartan (ARB) group. After
      operation, RN, CRN and ARB groups were intragastric administrated with RN (3
      mL/d), CRN (3 mL/d) and ARB [20 mg/(kg x d)] respectively. Each group randomly
      included 18 rats for statistical analysis. The histological changes of renal
      interstitial tissues were observed by HE, Masson and PAS staining. Total kidney
      collagen content was determined by measuring the amount of hydroxyproline. The
      mRNA of alpha-SMA, collagen I and fibronectin were reverse transcribed and
      quantified by real-time PCR. The expression of alpha-SMA protein was assessed by
      immunohistochemistry and Western blot analysis. RESULTS: In UUO model, the
      obstructed kidney showed typical features of renal tubulointerstitial fibrosis,
      such as severe tubular loss, dilation, atrophy, infiltration of inflammatory
      cells, interstitial matrix deposition (P < 0.05). Partial correlation assay
      showed that the expression of alpha-SMA was related to the renal tubular injury
      (r = 0.55; P < 0.05). Administration of RN, CRN and ARB improved
      tubulointerstitial damage and collagen matrix accumulation induced by UUO in
      different degree. The expression of the alpha-SMA at mRNA and protein levels were
      significantly increased in the UUO group (P < 0.05), which was also suppressed by
      treatment with RN, CRN and ARB in different degree. Moreover, more effective role
      in preventing fibrosis was observed in CRN group than when compared with that of
      RN group. CONCLUSION: RN and CRN can inhibit UUO-induced renal interstitial
      fibrosis in rats, and CRN treatment is more effective than RN in reducing
      interstitial fibrosis.

PMID- 22455127
TI  - [Protective effects of Z-ligustilide against cytotoxicity induced by Abeta25-35
      in neuron cells].
AB  - OBJECTIVE: To investigate the effects of Z-ligustilide (LIG) on Abeta25-35
      induced cytotoxicity in human neuroblastoma SH-SY5Y cells. METHODS: Cells were
      incubated with 0.1, 1.0, 2.5, 5.0 microg/mL LIG and then were exposed to 50
      micromol/L Abeta25-35 to induce cytotoxicity in SH-SY5Y cell to establish the AD
      model in vitro. Cell viability was test by MTT method. Pro- and anti-apoptosis
      protein levels were investigated by Western blot. RESULTS: After exposure to
      Abeta25-35, the cell viability decreased significantly, and the expression of pro
      apoptosis protein--Bax, cleaved caspase 3, cytochrome C, caspase 8 was up
      regulated while the anti-apoptosis protein Bcl-2 was down regulated. However, the
      treatment of LIG (0.1, 1.0, 2.5, 5.0 microg/mL) significantly restored these
      changes. CONCLUSION: LIG has the protective effect against cytotoxicity induced
      by in SH-SY5Y cells via inhibit the apoptosis induced by Abeta25-35.

PMID- 22455128
TI  - [Protective effects of morphine postconditioning on renal tissue against acute
      hypoxic-reoxygenation injury in rabbit].
AB  - OBJECTIVE: To investigate the protective effects of morphine postconditioning on
      the renal hypoxic/ reoxygenation injury in rabbit and the mechanisms involved.
      METHODS: Hypoxic/reoxygenation injury was induced with inhalation 8% O2 3 hours
      followed by breathing in air 48 hours. Thirty male white New Zealand rabbits were
      randomly divided into 3 groups: normal control group, hypoxic/reoxgenation group
      (H/R group) and morphine hypoxic postconditioning group (MO+H/R group). Animals
      in H/R and MO+H/R group received 5 mL of saline or morphine 3 mg/kg respectively
      before induction reoxygenation. The levels of serum creatinine (SCr) and blood
      urea nitrogen (BUN) were detected respectively at 48 hour after bypoxic and
      reoxgenation happened. Pathological changes in the different groups were also
      evaluated by light microscope. Renal apoptosis was determined quantitatively by
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      (TUNEL)methods. Result The SCr and BUN in H/R group and MO+ H/R group were much
      higher respectively when compared with those in the N group. The SCr and BUN in
      MO+H/R group were much higher compared with those in the H/R group. The renal
      pathological changes were more severe in the H/R group than that of MO+H/R group.
      Apoptosis phenomenon was lower in MO+H/R group than H/R group (P < 0.05).
      CONCLUSION: Morphine postconditioning can protect rabbit against acute renal
      hypoxic/reoxygenation injury by reducing renal apoptosis.

PMID- 22455129
TI  - [Effect of M007 mediated photodynamic therapy on proliferation of human
      osteosarcoma MG63 cells in vitro].
AB  - OBJECTIVE: To investigate the effect of a new photosensitizer, M007 mediated
      photodynamic therapy on proliferation of human osteosarcoma MG63 cells in vitro.
      METHODS: Human osteosarcoma MG63 cells were prepared as 1 x 10(6) /mL single-cell
      suspension, and 1 mL cells were transferred into 60 mL culture dish, then treated
      with 5 different gradient dosages (0, 2, 4, 8, 16 micromol/L) of M007 followed by
      photodynamic therapy or dark reaction for 10 min. The survival rate of the cells
      and the mode of cell death were detected by flow cytometry with the stain of
      Annexin V-FITC/PI. The effect on proliferation of survival cells was observed by
      MTT assay and colony-forming assay. RESULTS: M007 mediated photodynamic therapy
      induced the inactivation of MG63 human osteosarcoma cells in the way of late
      apoptosis/necrosis or becoming naked nucleus predominately. More than 90% MG63
      cells in M007-PDT group were dead under the treatment of 2-16 micromol/L M007.
      The survival rates of 4-16 micromol/L M007-PDT group were steadily less than 1%.
      The optical densities did not increase with extension of culture time in 2-8
      micromol/L M007-PDT group (P > 0.05). There were 16 survival alive cells found
      occasionally in 2 micromol/L M007-PDT group, but no colonies found in other
      groups. CONCLUSION: M007 mediated photodynamic therapy totally inactivated human
      osteosarcoma MG63 cells in vitro with the dosage more than 4 micromol/L.

PMID- 22455130
TI  - [Effect of protamine on VEGF expression in vitreous and serum of rats with
      diabetic].
AB  - OBJECTIVE: To study the effect of protamine on vascular endothelial growth factor
      (VEGF) expression in vitreous and serum of rats with diabetic. METHODS: 110 rats
      were included in the study, with 10 rats for normal control and the other 100 for
      diabetic models that induced by Streptozocin intraperitoneal injection. Then 80
      rats with diabetic were used as eight groups: three groups (T1, T2 and T3) for
      intravitreal injection of protamine (50 microg protamine in 5 microL), and the
      other five groups were used as control. After 3 months, the T1, T2 and T3 group
      received the first injection; after 4 months, the T2 and T3 group received the
      second injection; after 5 months, the T3 group received the third injection. The
      rats were executed one week after their last injection, the retinae of the rats
      were taken for HE staining, and expression of VEGF in the serum and vitreous were
      measured by ELISA. RESULTS: As diabetic developed, VEGF expression in both serum
      and vitreous rised (P < 0.05); after the second protamine injection, VEGF
      expression in vitreous began to decrease obviously (P < 0.05); but VEGF
      expression in the serum didn't change by protamine. Rat retinal HE staining for
      the diabetic model group revealed retinal thickening, local interrupt, inner and
      outer nuclear layer cell derangement and vascular proliferation, which were
      significantly improved for the treatment groups. CONCLUSION: Intravitreal
      injection of protamine reduced VEGF expression in vitreous of rats with diabetic,
      and protamine might be a new treatment for diabetic retinopathy, especially for
      retinal neovascularization.

PMID- 22455131
TI  - [Molecular identification, phylogenic and virulence analysis of a Legionella
      strain isolated from aquatic environment].
AB  - OBJECTIVE: CD-1 was isolated from aquatic environment, which grew with strict L
      cysteine dependence. In this study, we applied molecular methods to identify CD
      1, and animal test to understand its virulence. METHODS: To identify CD-1 strain,
      CD-1 strain was tested for genus-specific 16S rRNA of Legionella via PCR
      amplification, then its rpoB gene was sequenced for phylogenic analysis. To
      understand the virulence, CD-1 was detected for mip gene, which was an
      indispensable virulent gene of Legionella. Then, BABL/c mice were infected by CD
      1 in different dosages. RESULTS: For identification, CD-1 was positive for genus
      specific 16S rRNA of Legionella, while in the phylogenic tree CD-1 was a sister
      to Legionella longbeachae with high posterior probability (PP = 1.00). For the
      virulence analysis, CD-1 was positive for mip gene detection. In the animal test,
      all mice tested died when the infection dose of CD-1 strain reached 10(7) cfu/mL.
      CONCLUSION: CD-1 strain was identified to be Legionella longbeachae with strong
      virulence to BALB/c mice. It may be a potential virulent strain to human. This is
      the first strain of Legionella longbeachae isolated in Sichuan province, and this
      is the first virulence analysis of Legionella strain isolated from aquatic
      environment in China.

PMID- 22455132
TI  - [Ultrasound tissue characterization of hepatic fat in rats using radiofrequency
      signal analysis].
AB  - OBJECTIVE: To investigate the significance of multi-parameter quantitative
      evaluation of hepatic fat using ultrasound radiofrequency signal analysis.
      METHODS: Thirty two SD rats were divided into two groups, with 24 having fatty
      livers and 8 serving as normal controls. Radiofrequency signals were sampled with
      a 13-MHz ultrasound probe and digitized at 40 MHz in 16-bit resolution. Four
      statistical parameters of the radiofrequency envelope [Mean, Mean/SD ratio (MSR),
      skewness (SK), and kurtosis (KU)] within the ROI were calculated offline, and
      their ability to diagnose fatty liver was analyzed. RESULTS: The rats with fatty
      livers had greater Mean and MSR but lower skewness and kurtosis than the
      controls. The areas under the ROC curve of Mean, MSR, skewness and kurtosis for
      diagnosing fatty livers were 0.85, 0.96, 0.98, and 0.98 respectively. The
      sensitivity and specificity of Mean, MSR, skewness and kurtosis for diagnosing
      fatty livers were 70.8%/88.9%, 87.5%/100%, 95.8%/100% and 95.8%/100%
      respectively, whereas conventional ultrasound achieved only 68.2% in sensitivity
      and 66.7% in specificity. CONCLUSION: Compared with conventional ultrasound,
      radiofrequency signal analysis is more accurate in diagnosing fatty livers.

PMID- 22455133
TI  - [Expression of miR-130a in cisplatin resistant cell lines of ovarian cancer].
AB  - OBJECTIVE: To determine the expression of miR-130a in cisplatin resistant cell
      lines of ovarian cancer and its impact on cisplatin resistance. METHODS:
      Cisplatin resistant ovarian cancer cell lines were established by stepwise
      selection with gradual increase of cisplatin. MTT assay was applied to indentify
      the cisplatin resistant cell lines and determine their resistance index. The
      expression of miR-130a was measured by SYBR green real-time PCR. RESULTS: The
      resistance index of A2780/CIS1, A2780/CIS2 and SKOV3/CIS was 30.2, 5.3 and 24.5
      respectively. The SYBR green real-time PCR showed that miR-130a was over
      expressed in all of the cisplatin resistant cell lines (P < 0.05). The expression
      of miR-130a was 30.51 times higher in A2780/CIS1, 4.87 times higher in A2780/CIS2
      and 24.43 times higher in SKOV3/CIS than in their parental cell lines (P < 0.05),
      which was almost equally reflected in their resistance index. CONCLUSION: The
      over expression of miR-130a is associated with cisplatin resistance of ovarian
      cancer. Inhibiting miR-130a expression may help reverse the cisplatin resistance
      of ovarian cancer. miR-130a is expected to be a new potential target of genetic
      therapy for cisplatin resistant ovarian cancer.

PMID- 22455134
TI  - [Distinguishing benign from malignant incidental adrenal lesions in enhanced CT
      imaging].
AB  - OBJECTIVE: To characterize the differences in radiologic features between benign
      and malignant adrenal lesions. METHODS: Enhanced multiple-slice spiral CT images
      of 99 patients with adrenal tumors were reviewed retrospectively, investigating
      into morphological features of different kinds of adrenal lesions with Wash-in
      Amplitude (WA, venous phase attenuation-unenhanced attenuation) and relative wash
      in ratio (RWR, WA/artery phase attenuation). RESULTS: A combination of threshold
      in diameter = 3.2 cm, unenhanced attenuation = 24 HU, and RWR value = 0.879
      produced 94.28% sensitivity and 98.43% specificity in diagnosing adenomas.
      CONCLUSION: Enhanced CT imaging improves diagnostic accuracy of incidental
      adrenal lesions.

PMID- 22455135
TI  - [The influence of heartbeat acceptance window settings on left ventricular
      function and perfusion parameters].
AB  - OBJECTIVE: To evaluate the influence of heartbeat acceptance window settings on
      left ventricular function and perfusion parameters of the arrhythmia patients
      during gated myocardial perfusion imaging. METHODS: Twenty eight fibrillation
      patients were consecutively recruited to undergo myocardial perfusion SPECT. The
      Concurrent Imaging software was used to create 3 separate SPECT studies with
      heartbeat acceptance window of 20%, 60% and 100% respectively. The software
      created the 3 studies separately rather than a rearrangement of an original list
      mode acquisition. After reconstruction by Astonish, end-diastole volume (EDV) and
      end-systolic volume (ESV), left ventricular ejection fraction (LVEF), sum stress
      score (SSS), and sum rest score (SRS) were calculated with Quantitative Gated
      SPECT (QGS). Analyses of variance were performed using SPSS to compare the
      differences in EDV, ESV, EF, SSS, and SRS among the three studies. RESULTS: 85.7%
      of the 28 patients had abnormal perfusing. No statistical differences were found
      in EDV, ESV, EF, SSS, and SRS among the 3 studies. But the collection time was
      40.5 min, 25.6 min and 15.0 min for heartbeat acceptance window of 20%, 60% and
      100% respectively. CONCLUSION: Heartbeat acceptance window setting does not have
      a significant effect on EDV, ESV, EF, SSS, and SRS values. The wider the window
      is set, the shorter the collection time is.

PMID- 22455136
TI  - [The trends and progress in the comprehensive treatments of urological
      malignance].
AB  - Urological malignance include a group of cancers of urinary system, the incidence
      of urological cancer shows increasing trend, while the increasing progress in
      both surgical and non-surgical treatments leads to better therapeutic effects to
      the patients of urological oncology. For example, more and more prostatic cancers
      are promptly diagnosed in the stage of organ-confined disease which is suitable
      for curable therapies, and the surgical technique of radical prostatectomy is
      well established and being optimized to guarantee the outcome of prostate cancer
      with the decrease of surgical complication. The improvements of radical
      cystectomy, along with the optimization of peri-operative intervention, are
      providing more curable opportunity to elderly and high operative risk patients of
      bladder cancer. The breakthrough of basic research on molecular pathogenesis of
      renal cell carcinoma, leads to the innovative clinical translation of molecular
      targeted therapy in the treatment of metastatic renal cancer. The great success
      of research and development on targeted therapy now are attracting more and more
      clinical and basic researches which possibly lead to promising novel treatments
      to urological malignance in the coming future. For the best clinical practice in
      urological oncology, it is necessary to pay tremendous attention on the advance
      of both clinical study and laboratory research, which would be the better way to
      more effectively improve the survival and prognosis of the patients of urological
      malignance with comprehensive treatments.

PMID- 22455137
TI  - [Expression of BNIP3 and its correlations to HIF-1alpha and VEGF in clear cell
      renal cell carcinoma].
AB  - OBJECTIVE: To study the expressions of proapoptosis protein BNIP3 and its
      correlation with HIF-1alpha and VEGF in clear cell renal cell carcinoma (ccRCC).
      METHODS: The expression levels of BNIP3, HIF-1alpha and VEGF were examined by two
      step immunohistochemical staining with tissue chip technique in 104 cases of
      ccRCC and in 48 cases of normal renal tissues. The correlation of BNIP3
      expression with HIF-1alpha and VEGF was analyzed. RESULT: The positive expression
      rates of BNIP3, HIF-1alpha and VEGF were 36.5%, 61.5%, and 69.2% in ccRCC, while
      were 12.5%, 8.3%, and 12.5% in paracancerous normal renal tissue, respectively.
      The expression of both HIF-1alpha and VEGF were not significantly increased in
      BNIP3 positive tumors in comparison with BNIP3 negative counterpart (P > 0.05),
      but there was a significant correlation between HIF-1alpha and VEGF (P < 0.05).
      CONCLUSION: The lower expression level of BNIP3 is not coincident with the high
      level of HIF-1alpha and VEGF in clear cell renal cell carcinoma.

PMID- 22455138
TI  - [Prediction and screening of CTGF secondary structure and receptor-binding
      domain].
AB  - OBJECTIVE: To analyze the secondary structure of connective tissue growth factor
      (CTGF) for the prediction and screening of candidate receptor-binding domain of
      CTGF. METHODS: Bioinformatics method was employed to predict and screen CTGF
      receptor-binding domain based on the analysis of secondary structure of CTGF, and
      its hydrophilicity and physical property. RESULTS: The results showed that the
      candidate receptor-binding domains locate in 96-102, 104-112, 257-272 segments,
      the corresponding amino acid sequences are TAKDGAP, IFGGTVYRS and
      IRTPKISKPIKFELSG, respectively. CONCLUSION: There were 3 candidate receptor
      binding domains of CTGF, which might be the targets for newly antagonistic
      micromolecule polypeptide of CTGF.

PMID- 22455139
TI  - [Primary leiomyosarcoma of the kidney: a clinicopathological study of 13 cases at
      a high-volume institution].
AB  - OBJECTIVE: To analyze the clinical characteristics, treatment, and survival of
      adult patients with renal leiomyosarcoma treated at our institution during the
      past 13 years. METHODS: A retrospective review was performed to collect the
      demographic distribution, clinical manifestation, treatment, and outcome data
      about 13 adult patients of renal leiomyosarcoma treated at our institution from
      January 1996 to January 2008. The clinical parameters were analyzed to determine
      the effects on survival by logistic regression. RESULTS: Mean age at diagnosis
      was 45.7 years (range 20 to 71), and 61.5% (8/13) were female. Mean tumor
      diameter was (11.1 +/- 10.2) cm (range 3 to 34 cm), 53.9% (7/13) had direct
      invasion of renal capsule, and 23.1% (3/13) had lymphovascular invasion. The
      follow-up information of 11 cases was available, and duration of follow-up was an
      average of 39.2 (range 9-81) months. The overall survival (OS) rate at 1, 3, and
      5 years was 81.8%, 54.5%, and 16.2% respectively. 8 (72.7%) patients developed
      metastasis, and 9 (81.8%) patients eventually died. The survival of the patients
      did not show correlations with age, pathologic grade, extrarenal component,
      lymphovascular invasion, complete resection or not and chemotherapy or not.
      CONCLUSION: Primary renal leiomyosarcoma has a poor survival prognosis regardless
      of the underlying histological and clinical features.

PMID- 22455140
TI  - [Survival analysis of interferon-alpha on locally advanced clear cell renal cell
      carcinoma after radical nephrectomy].
AB  - OBJECTIVE: To evaluate the effect of interferon-alpha (IFN-alpha) on locally
      advanced clear cell renal cell carcinoma (ccRCC) after radical nephrectomy in
      terms of tumor progression free survival (PFS) and overall survival (OS).
      METHODS: 176 cases with locally advanced ccRCC were followed up in West China
      Hospital from 1999 to 2007. All patients were divided into two groups according
      to whether treated with IFN-alpha as adjuvant therapy. PFS and OS were analyzed
      with Kaplan-Meier method and Cox regression model. RESULTS: Median follow-up was
      48 months, 53 cases of disease progressed, and 37 were dead. Mortality rate
      within treatment and observed groups were 44.3% and 18.6%, respectively (P <
      0.001). There were significant differences between the two groups in PFS [(59.12
      +/- 5.04) months vs. (81.42 +/- 5.84) months, P = 0.005] and OS [(74.66 +/- 4.77)
      months vs. (85.18 +/- 4.92) months, P = 0.031]. Cox regression model demonstrated
      that IFN-alpha, as adjuvant therapy after surgery, was an independent negative
      risk factor for the prognosis of locally advanced clear cell renal cell
      carcinoma. CONCLUSION: IFN-alpha was ineffective in locally advanced ccRCC after
      radical nephrectomy in terms of PFS and OS, and there is no evidence that IFN
      alpha could be considered as adjuvant therapeutic drug.

PMID- 22455141
TI  - [Comparison of outcomes and complications between antegrade and retrograde
      approach to open radical prostatectomy].
AB  - OBJECTIVE: To compare the operative outcomes and complications between an
      anterograde versus retrograde approach to open radical retropubic prostatectomy
      (RRP); METHODS: Retrospectively analyze the clinical data and follow-up results
      of 76 prostate cancer patients who received radical retropubic prostatectomy from
      April 2006 to May 2011. According to the resection approach of prostate, the
      patients were divided into two groups, antegrade RRP group (45 cases) and
      retrograde RRP group (31 cases). The operative outcomes and complications between
      two groups were analyzed. RESULTS: There was no peri-operative death and cancer
      specific death during the follow-up. Eleven cases were found positive surgical
      margin, 5 (11.1%) in antegrade group, 6 (19.3%) in retrograde group. The
      estimated blood loss of these 76 operations were 230-1200 mL [mean (367.2 +/-
      132.4) mL], (324.0 +/- 70.3) mL in antegrade group and (429.8 +/- 172.3) mL in
      retrograde group, respectively. The volume of blood loss between the two groups
      was significantly different. The durations of follow-up for the patients were 2
      63 months [(24.22 +/- 13.21) months), 4 cases showed biochemical failure with
      criterion as prostate specific antigen > 0.2 microg/L, 2 patients had stress
      incontinence of antegrade RRP group and 1 patient had permanent incontinence of
      retrograde RRP group, there were no significant difference between the two
      groups. CONCLUSIONS: Antegrade radical prostatectomy provides a low incidence of
      complications, reduced blood loss for localized prostatic cancer.

PMID- 22455142
TI  - [Critical analysis on risk factors of postoperative in-hospital complications in
      radical cystectomy of bladder cancer].
AB  - OBJECTIVE: To evaluate the risk factors associated with the in-hospital
      complications of radical cystectomy. METHODS: The records of 128 consecutive
      patients who underwent radical cystectomy from November 2006 to October 2009 were
      reviewed. Preoperative, intraoperative risk variables were defined based on
      POSSUM score and APACHE II score. ASA score and m-ACCI score were used to
      evaluate the co-mobidities. All variables were analyzed to evaluate the risk
      factors associated with in-hospital complications of radical cystectomy. RESULTS:
      In the 128 patients undergoing radical cystectomy, 58 patients (45.31%) had
      complications, with 51 (39.84%) minor complicatons and 7 (5.47%) major
      complications. Wound dehiscence or unhealing (22.66%), infection (20.31%) and
      ileus (17.19%) were the most common complications. The risk factors related to
      the in-hospital complications of radical cystectomy are age > or = 65 yr. (P <
      0.001,OR = 1.067), volume of intraoperative blood transfusion > or = 600 mL (P =
      0.023, OR = 1.001), m-ACCI score (P < 0.001, OR = 1.583), ASA score > or = III (P
      = 0.003, OR = 2.411), partial cystectomy history (P = 0.025 OR = 2.444),
      intraoperative heart rate > 120 beats/min (P < 0.001, OR = 11.861). CONCLUSIONS:
      Wound complication, postoperative infection and ileus are the most common
      complications of radical cystectomy. Age, volume of intraoperative blood
      transfusion, m-ACCI score, ASA score, partial cystectomy history and
      intraoperative heart rate are significant risk factors.

PMID- 22455143
TI  - [Estimating glomerular filtration rate based on serum cystatin C].
AB  - OBJECTIVE: To develop an estimating formula for glomerular filtration Rate (GFR)
      based on serum cystatin C in patients with chronic kidney disease (CKD). METHODS:
      Clinical characteristics of 242 CKD patients were collected. The patients were
      randomly divided into modeling group and model validation group. The rGFR
      obtained from 99mTc-DTPA clearance rate was used as a reference value of GFR. s
      cystatin C was detected by latex enhanced immunoturbidimetric method. Preliminary
      linear regression analysis followed by multiple linear regression were performed
      to investigate the association between s-cystatin C and rGFR. The validity of the
      estimation formula was tested in the model validation group in comparison with
      Hoek formula and Orebro formula. RESULTS: With standardised countdown conversion,
      s-cystatin showed linear correlation with rGFR, with a correlation coefficient of
      0.773. The multiple correlation coefficient, determination coefficient, adjusted
      R square and std. error of the estimation model were 0.863, 0.745, 0.742, and
      0.207, respectively. The residuals P-P probability plot analysis showed that the
      model residuals fitted into normal distribution with homogeneity of variance.
      Theeformula was: eGFR = 67/s-cystatin C +3. No significant difference was found
      between the distribution of eGFR and rGFR. Our formula had an accuracy of 30% and
      50%, which were no less than those obtained from Hoek formula and Orebro formula.
      The new formula also had acceptable bias and high precision. The Bland-Altman
      analysis and ROC curve analysis showed good applicability of the new formula.
      CONCLUSION: The GFR prediction formula we established has a good prediction
      performance as comparised with other formulae, which could be used in measuring
      GFR in CKD patients.

PMID- 22455144
TI  - [Determination of 44 organophosphorus pesticides in food by SPE disk extraction
      capillary gas chromatography with pulsed flame photometric detection].
AB  - OBJECTIVE: To develop a method for the simultaneous determination of 44
      organophosphorus pesticides in food by SPE disk extraction-capillary gas
      chromatography with pulsed flame photometric detection. METHODS: Organophosphorus
      pesticides in food were extracted ultrasonically with water. Then the extract was
      cleaned-up with SPE disk and eluted with ethyl acetate. Finally the eluent was
      condensed to 1mL under N2 at 55 degrees C. Gas chromatography was applied for
      quantitative detection of the organophosphorus pesticides in the sample. RESULTS:
      The linear range of the method for all the pesticides were in the range of 0.01
      0.5 mg/kg with correlation coefficients of 0.992-1.000. The detection limits of
      the method were in the range of 0.0005-0.01 mg/kg. The recoveries for most
      pesticides were 60%-120% with relative standard deviations of less than 15%.
      CONCLUSION: The method is simple, sensitive, environmentally friendly and
      suitable for the determination of organophosphorous pesticides in food.

PMID- 22455145
TI  - [Determination of canthaxanthin and astaxanthin in egg yolks by reversed phase
      high performance liquid chromatography with diode array detection].
AB  - OBJECTIVE: A method using reversed phase high performance liquid chromatography
      (RP-HPLC) coupled with diode array detector (DAD) was developed for the
      simultaneous determination of canthaxanthin and astaxanthin in egg yolks.
      METHODS: Samples were extracted with acetonitrile in ultrasonic bath for 20
      minutes and then purified by freezing-lipid filtration and solid phase extraction
      (SPE). After being vaporized to dryness by nitrogen blowing and made up to volume
      with methanol, the extract solution was chromatographically separated in C18
      column with a unitary mobile phase consisting of acetonitrile. The proposed
      method was validated in terms of linearity, precision, accuracy, and limit of
      detection (LOD). RESULT: Regression analysis revealed a good linearity between
      peak area of each analyte and its concentration (r > or = 0.998). The intra- and
      inter-day relative standard deviations (RSDs) were less than 3.6% and 5.2%,
      respectively. LODs of canthaxanthin and astaxanthin were 0.035 and 0.027
      microg/mL (S/N = 3). The average recoveries of canthaxanthin and astaxanthin were
      91.5% and 88.7%. CONCLUSION: The proposed method is simple, fast and easy to
      apply.

PMID- 22455146
TI  - [Evaluation and optimization of cerebral vaospasm model with subarachnoid
      hemorrhage].
AB  - OBJECTIVE: To determine biphasic changes of cerebral vasospasm (CVS) after
      subarachnoid hemorrhage (SAH) and its association with ischemic neurological
      injuries. METHODS: 55 adult male New-Zealand rabbits weighing 2.0-2.5 kg were
      randomly divided into 2 groups: control and SAH groups(including 10 subgroups at
      different sacrificed time: 12 h, 24 h, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d. 8 d, 9 d).
      The rabbits were induced into cisterna magna by withdraw of 0.5 mL cerebrospinal
      fluid followed with administration of 2 mL saline (control group) or fresh
      unheparinised autologous arterial blood (SAH group). The neurobehavioral scores
      were measured every day. The middle basilar artery and hippocampus were examined
      by optical microscope with HE stain, measuring coefficient of corrugation (CC)
      and survival number of hippocampal CA1 neurons. The neurological injury was
      assessed by injured hippocampal CA1 neurons and neurobehavioral scores. RESULTS:
      Severe and moderate vasospasms were detected in basilar arteries of the rabbits
      in the SAH group. Compared with the control group, the CC of the rabbits of the
      SAH group decreased significantly at 12 h, 24 h, 2 d, 3 d, and 4 d (P < 0.05).
      The recovery on day 5 was temporary and the CC plunged again from day 6 (P <
      0.05). No statistical significance was found in the numbers of survived
      hippocampal CA1 neurons between the two groups (P > 0.05). There was no
      correlation between hippocampal CA1 survival neurons and cerebrovasospasm
      progression. CONCLUSION: Acute vasospasm occur from 12 h to day 4, which is
      followed by delayed vasospasm from day 5 to day 9. The hippocampal CA1,
      histopathological measurement is not suitable for evaluating brain injury after
      SAH.

PMID- 22455147
TI  - [Osteoarthrosis--where are we going in 2012].

PMID- 22455148
TI  - [Imaging in osteoarthritis].
AB  - Plain radiography remains useful for the diagnosis of osteoarthritis, even if it
      is not always essential. It is moreover poorly correlated with symptoms, as it
      reflects rather the accumulation of damage then active processes. Similarly, it
      is a poor indicator of the progression of osteoarthritis. Modem imaging,
      particularly MRI, has allowed us to understand better the evolving processes,
      demonstrating a good correlation with symptoms and a better predictive value of
      clinical course. It has gradually replaced standard radiography in the study
      because it directly demonstrates sequelae and the active processes in all the
      structures of the joint. It remains clinically indicated only to exclude an
      alternative diagnosis or to determine a possible complication of osteoarthritis.

PMID- 22455149
TI  - [Exercise--sports and osteoarthritis].
AB  - Osteoarthritis (OA) is currently a major health problem, both with an important
      individual and socio-economical impact. The diagnostic of osteoarthritis is both
      clinical and radiological, without a strong correlation between symptoms and
      radiographic findings. Participation in sports increases the risk of joint
      overuse or injuries potentially leading to posttraumatic osteoarthritis.
      Conversely, sport is a recognized therapeutic and probably also a preventive tool
      against osteoarthritis, with a positive influence on weight, muscle strength and
      possibly synovial inflammation. In general, sport should be encouraged
      individually with an appropriate program and a correct intensity.

PMID- 22455150
TI  - [Role of slow-acting anti-arthritic agents in osteoarthritis (chondroitin
      sulfate, glucosamine, hyaluronic acid)].
AB  - Osteoarthritis (OA) is one of the major causes of pain and of outpatient's
      clinics. 15 years ago, physiopathology of OA and its potential therapeutic
      targets were announced to be better understood, but the results of therapeutic
      trials were finally not as convincing as expected. Slow Acting Drugs (SADs) are
      part of the treatments evaluated in OA. Even if evidence based medicine is low,
      positive effects of SADs have been observed. We can reasonably propose these
      treatments for a short test period. It can sometimes enable us to decrease the
      dosage of others treatment such as NSAIDs. In any case, the physician must
      properly inform the patient about products available in Switzerland and must be
      aware of degrees of purity and costs of the products available on the intemet.

PMID- 22455151
TI  - [Joint-preserving surgical options in osteoarthritis].
AB  - Joint-preserving surgery aims to correct the mechanical disbalances leading to
      the inhomogenous load distribution across joint lines, potentially leading to
      osteoarthritis. The possibilities of axial corrections at the knee have been
      known for years. A better pathophysiologic understanding of the disbalances
      leading to coxarthrosis has, more recently, allowed for the development of joint
      preserving approaches, for instance in situations of excessive (impingement) or
      insufficient (dysplastic) femoro-acetabular coverage. On the opposite, in the
      absence of a mechanical defect, or if osteoarthritis is already present, joint
      preserving surgery has little chances of success.

PMID- 22455152
TI  - [Lumbar spinal stenosis: clinical course, pathophysiology and treatment].
AB  - The lumbar spinal stenosis is a radiological description of a pathology that can
      present clinically by a neurogenic intermittent claudication; its diagnosis is
      mainly clinical. After listing the main criteria allowing the clinician to make a
      diagnosis, a review of available treatments is proposed. There are few quality
      studies and an empirical approach is often necessary. In severe cases, very
      disabling despite correct treatment, a surgical approach may be considered and
      discussed with the patient to avoid failure, sometimes linked to excessive
      expectations.

PMID- 22455153
TI  - [Postural hygiene and ergonomic advices for low back pain: rethinking our
      practice].
AB  - In recent years, scientific understanding of low back pain has increased
      considerably, sometimes shoving concepts thought to be unshakable. If we consider
      postural hygiene,whose techniques were conceptualized in the 70's and are still
      widely used, not only some axioms were not confirmed but some evidences suggest
      that it may sometimes have deleterious effects. After reviewing these elements it
      appears that there is no simple formula applicable to all patients with low back
      pain. Instead we offer food for thought so that every therapist can adapt his
      practice on an individual basis.

PMID- 22455154
TI  - [Pit falls in the emergency walk-in clinic: the spine].
AB  - Spine is always a great deal in tramatology. Complete clinical exam associated to
      plain Xray is the best challenge. CT-scan is preferred when there is
      osteoarthritis. IRM is used to check ligaments ("coup du lapin") or for medullar
      contusion.

PMID- 22455155
TI  - [Aneamia secondary to geophagia in a rich country? A case report].
AB  - Geophagia, eating of earth, is a relative frequent practice in several countries
      and especially in the African and South American mainlands. In some cases,
      migrant people continue this practice in the host country. Geophagia has some
      positive effects, presumed or real, and several harmful effects with significant
      health impacts. We relate the history of young patient of Cameroonian origin who
      consults for chonic fatigue, abdominal pain and menorrhagia. Laboratory tests
      show a severe aneamia with iron deficiency.

PMID- 22455156
TI  - [The independence of medicine in prison: a small epilogue of the case Rappaz].

PMID- 22455157
TI  - [Additional euthanasia in the Netherlands].

PMID- 22455158
TI  - [The smoker is a very sweet squirrel in cage].

PMID- 22455159
TI  - [Prevent the epidemic of dementia].

PMID- 22455160
TI  - [Health insurance: the beginning of the end].

PMID- 22455161
TI  - Together everyone achieves more.

PMID- 22455162
TI  - Start of a new era in South Dakota medical education.

PMID- 22455163
TI  - Management of acute sports injuries and medical conditions by South Dakota high
      school head coaches: assessment via case scenarios.
AB  - BACKGROUND: When medical coverage does not exist at games and practices, coaches
      are often responsible for the management of acute conditions. The question that
      arises is whether they make proper medical decisions concerning the health and
      safety of their athletes. The purpose of this study was to assess high school
      head coaches' decision-making skills related to acute medical condition
      management through the use of case scenarios. METHODS: A cover letter/web link to
      the web-based survey was e-mailed to all 2008-2009 school year South Dakota high
      school head athletic coaches. RESULTS: Head coaches were found to be responsible
      for the immediate care of injured athletes at practice (87.2 percent) and home
      competitions (72.3 percent). Less than 75.0 percent of coaches reported feeling
      "prepared" or "somewhat prepared" to handle 11 of the 16 types of acute athletic
      injuries and medical conditions presented, with less than 75.0 percent of coaches
      giving "appropriate" or "overly cautious" responses to eight of the 17 cases.
      Little to no relationship was found between perceived level of preparedness for
      treating various conditions and appropriateness of responses. A significant
      difference was found in appropriateness of decisions based on level of athlete
      (68.9 percent starters, 79.3 percent non-starters) and event situation (66.5
      percent important events, 76.6 percent non-important events). CONCLUSIONS: In
      South Dakota, high school coaches are most often responsible for the initial
      management of acute injuries; yet, a large percentage of coaches did not feel
      "prepared" to manage various conditions and/or gave "inappropriate" responses to
      multiple cases. Furthermore, the level of athlete and the event situation may
      influence coaches' decisions. Further education may include the proper management
      of head and neck injuries, multiple concussions, dislocations, heat emergencies,
      eye injuries and internal organ injuries. Health care workers can be an integral
      part of training coaches in the care of acute conditions, as well as providing
      practice and event coverage.

PMID- 22455164
TI  - Vitamins: the good, the bad and the...deadly?

PMID- 22455165
TI  - Fecal immunochemical testing (FIT) demonstrates success in colorectal cancer
      prevention.

PMID- 22455166
TI  - Health care in its right mind: medical harm and the knowledge revolution part 3-
      mindfulness and medical knowledge.
AB  - The crisis of medical knowledge has been precipitated by the complexity of health
      care, made up by overuse (30 to 40 percent waste), underuse (best evidence 10 to
      20 percent of the time) and misuse (adverse events in 25 to 33 percent of
      hospital admissions).

PMID- 22455167
TI  - Pharmacy services prepares to launch online prior-authorization tool.

PMID- 22455168
TI  - Oncology nurses help patients get through one of the most difficult types of
      cancer.

PMID- 22455169
TI  - Advancements in head and neck cancer. Better treatment options offer more
      promise.

PMID- 22455170
TI  - What challenges do you face in caring for patients with head and neck cancer?

PMID- 22455171
TI  - Managing chemotherapy-related cognitive impairment.

PMID- 22455172
TI  - The case of the rapid rituximab regimen.

PMID- 22455173
TI  - Cancer during pregnancy can be treated successfully.

PMID- 22455174
TI  - Addressing the issues of management and quality.

PMID- 22455175
TI  - Perceptions of changes in practice following peer review in the National Chronic
      Obstructive Pulmonary Disease Resources and Outcomes Project.
AB  - PURPOSE: The purpose of this paper is to examine perceptions of local service
      change and concepts of change amongst participants in a UK nationwide randomised
      controlled trial of informal, structured, reciprocated, multidisciplinary peer
      review with feedback to promote quality improvement: the National Chronic
      Obstructive Pulmonary Disease Resources and Outcomes Project (NCROP).
      DESIGN/METHODOLOGY/APPROACH: The paper takes the form of a qualitative study,
      involving semi-structured interviews with 43 hospital respiratory consultants,
      nurses and general managers at 24 intervention and 11 control NCROP sites.
      Thematic analysis resulted in adoption of Joss and Kogan's quality indicators as
      an analytic framework. FINDINGS: The paper finds that peer review was associated
      with positive changes, which may lead to sustained service improvement.
      Differences existed in perceptions of change among clinicians and between
      clinicians and managers. "Generic changes" (e.g. changes in interpersonal
      relations or cultural changes), were often not perceived as change. RESEARCH
      LIMITATIONS/IMPLICATIONS: The study highlights the significance of generic change
      in evaluations of change processes. Most participants were clinicians limiting
      inter-professional comparisons. Some clinical staff failed to recognise changes
      they accomplished or their significance, perceiving change differently to others
      within their professional group. These findings have implications for policy and
      research. They should be considered when developing frameworks for assessing
      quality improvements and staff engagement with change. ORIGINALITY/VALUE: This is
      the first qualitative study exploring participants' experience of peer review for
      quality improvement in healthcare. The study adds to previous research into UK
      health service improvement, which has had a more restricted focus on inter
      professional differences.

PMID- 22455176
TI  - A pilot study of satisfaction in oncology nursing care: an indirect predictor of
      quality of care.
AB  - PURPOSE: Although "satisfaction" is not easy to define, excellence in health care
      is impossible without professional/patient satisfaction, so this paper aims to
      report on a pilot study designed in order to evaluate the degree of nursing staff
      satisfaction with the implementation of measures to improve quality of care.
      DESIGN/METHODOLOGY/APPROACH: The project consisted of several phases: writing
      protocols of care; training of nursing staff in their management; and a cross
      sectional study to evaluate nursing staff satisfaction with them. The design of
      the survey consisted of a 16-item Likert scale, which had to be auto filled. A
      factorial analysis to simplify and validate the tools was used, using statistical
      analyses with SPSS software 8.0. PRACTICAL IMPLICATIONS: The results are
      applicable to young small oncological units with high degree of variability in
      patient care. The study showed that nursing staff satisfaction with new
      improvement measures taken improves safety and finally quality of care. FINDINGS:
      The study obtained four dimensions (D) explaining 100 percent of variance. Each
      dimension with several items: D1: "Nursing job quality" explaining 48.4 percent
      of variance; D2: "Satisfaction with the knowledge"; D3: "Nursing job
      feelings/perceptions"; D4: "Nursing communication with doctors/patients". It
      provided a direct point of view of each nurse, knowledge about problems
      encountered daily and demonstration of how a simple/convenient method is useful
      to engage the staff in decision-making-process and implementation of new
      strategies or to promote the integration of basic aspects of health management in
      daily clinical practice. ORIGINALITY/VALUE: This is the first study evaluating
      nursing staff satisfaction with new improvement measures taken in a small medical
      unit, aiming at quality of care benefits. Very promising results were obtained
      although the sample size was small.

PMID- 22455177
TI  - Context challenges the champion: improving hip fracture care in a Swedish
      university hospital.
AB  - PURPOSE: The purpose of this paper is to describe and explain a clinician-led
      improvement of a hip fracture care process in a university hospital, and to
      assess the results and factors helping and hindering change implementation.
      DESIGN/METHODOLOGY/APPROACH: The paper has a mixed methods case study design.
      Data collection was guided by a framework directing attention to the content and
      process of the change, its context and outcomes. FINDINGS: Using a
      multiprofessional project team, beneficial changes in the early parts of the care
      process were achieved, but inability to change surgical staff work practices
      meant that the original goal of operating patients within 24 hours was not
      reached. After three years, top management introduced a hospital-wide process
      improvement programme, which "took over" the responsibility for improving hip
      fracture care. RESEARCH IMPLICATIONS/LIMITATIONS: A clear vision why change is
      needed and what needs to be done, which is well communicated by a respected
      clinical leader, can motivate personnel, but other influences are also needed to
      bring about change. Without a plan agreed and supported by top management,
      changes are likely to be limited to parts of the process and improvements to
      patient care may be minimal. These and other findings may be applicable to
      similar situations in other services. ORIGINALITY/VALUE: This case study is an
      illustration of both the strengths and the weaknesses of a "bottom-up, clinician
      champion-led improvement initiative" in a complex university hospital.

PMID- 22455178
TI  - Estimating ICU bed capacity using discrete event simulation.
AB  - PURPOSE: The intensive care unit (ICU) in a hospital caters for critically ill
      patients. The number of the ICU beds has a direct impact on many aspects of
      hospital performance. Lack of the ICU beds may cause ambulance diversion and
      surgery cancellation, while an excess of ICU beds may cause a waste of resources.
      This paper aims to develop a discrete event simulation (DES) model to help the
      healthcare service providers determine the proper ICU bed capacity which strikes
      the balance between service level and cost effectiveness.
      DESIGN/METHODOLOGY/APPROACH: The DES model is developed to reflect the complex
      patient flow of the ICU system. Actual operational data, including emergency
      arrivals, elective arrivals and length of stay, are directly fed into the DES
      model to capture the variations in the system. The DES model is validated by open
      box test and black box test. The validated model is used to test two what-if
      scenarios which the healthcare service providers are interested in: the proper
      number of the ICU beds in service to meet the target rejection rate and the extra
      ICU beds in service needed to meet the demand growth. FINDINGS: A 12-month period
      of actual operational data was collected from an ICU department with 13 ICU beds
      in service. Comparison between the simulation results and the actual situation
      shows that the DES model accurately captures the variations in the system, and
      the DES model is flexible to simulate various what-if scenarios.
      ORIGINALITY/VALUE: DES helps the healthcare service providers describe the
      current situation, and simulate the what-if scenarios for future planning.

PMID- 22455179
TI  - Follow-up in head and neck cancer: patients' perspective.
AB  - PURPOSE: The purpose of this paper is to determine head and neck cancer patients'
      perspective of their follow-up regime and to suggest ways in which these
      perspectives can be incorporated into current practice.
      DESIGN/METHODOLOGY/APPROACH: This is a prospective survey-based study. A total of
      263 patients consecutively attending a head and neck cancer clinic completed a
      survey about their experience of the follow-up process in the post-treatment
      period between January 2009 and October 2009. FINDINGS: The paper finds that, of
      the patients, 67 per cent (n = 176) felt that the clinic met the goals they hoped
      would be achieved during their visit; 84 per cent (n = 221) felt that their
      follow-up visits were too frequent. In total 60 per cent (n = 159) were booked to
      see both an allied health professional and the attending clinician. Of these, 84
      per cent (n = 134/159) felt that issues addressed at follow-up with the clinician
      duplicated those addressed by the allied healthcare professionals. When asked
      about their opinion of a less intensive follow-up system based on patients
      reporting problems and requesting appointments, 73 per cent (n = 192) favoured
      it. When asked who they would like to contact first in such a system, most
      patients (n = 118, 45 per cent) stated a clinical nurse specialist. PRACTICAL
      IMPLICATIONS: Current follow-up regimes may be too prescriptive in their approach
      without taking patient perspective into consideration. Patients felt that being
      seen intensively for the first year, then having visits tapered off over the next
      two years and finally being seen according to symptoms thereafter to be
      appropriate and felt that this represented an overall better system.
      ORIGINALITY/VALUE: These data suggest the need for a more patient-focused,
      individualised approach to follow-up in head and neck cancer.

PMID- 22455180
TI  - Public health laboratory quality management in a developing country.
AB  - PURPOSE: The article aims to give an overview of the system of public health
      laboratory quality management in Thailand and to produce a strengths, weaknesses,
      opportunities and threats (SWOT) analysis that is relevant to public health
      laboratories in the country. DESIGN/METHODOLOGY/APPROACH: The systems for
      managing laboratory quality that are currently employed were described in the
      first component. The second component was a SWOT analysis, which used the
      opinions of laboratory professionals to identify any areas that could be improved
      to meet quality management systems. FINDINGS: Various quality management systems
      were identified and the number of laboratories that met both international and
      national quality management requirements was different. The SWOT analysis found
      the opportunities and strengths factors offered the best chance to improve
      laboratory quality management in the country. PRACTICAL IMPLICATIONS: The results
      are based on observations and brainstorming with medical laboratory professionals
      who can assist laboratories in accomplishing quality management.
      ORIGINALITY/VALUE: The factors derived from the analysis can help improve
      laboratory quality management in the country. This paper provides viewpoints and
      evidence-based approaches for the development of best possible practice of
      services in public health laboratories.

PMID- 22455181
TI  - Modeling the effects of victim behavior and moral character on prosecutors'
      charging decisions in sexual assault cases.
AB  - Prior research, modeling the effects of the victim's behavior and character on
      prosecutors' charging decisions, has used either a dichotomous variable that
      reflects the presence of any risky behavior or moral character issues or an
      additive index that captures the number of related items in a case file. We
      suggest that these measures do not adequately identify the specific issues that
      prosecutors take into consideration when making charging decisions. Using data on
      666 sexual assault cases that resulted in arrest in three urban jurisdictions and
      a multivariate modeling strategy, we examine specific risk-taking behaviors and
      issues related to the victim's moral character in an effort to determine if
      certain behaviors and characteristics have a more substantial effect on charging
      decisions than others. We also examine the extent to which the effects of these
      blame and believability factors vary based on the nature of the cases. Our
      results reveal that although charging decisions in stranger cases are largely
      determined by legally relevant factors, these decisions in nonstranger cases are
      affected by several legally irrelevant victim characteristics: whether the victim
      had a prior criminal record, whether the victim had been drinking alcohol prior
      to the assault, and whether the victim invited the suspect to her residence.
      Further analysis, however, revealed that only the victim's prior record had a
      differential effect on charging decisions in cases involving strangers and
      nonstrangers and in aggravated and simple rape cases. Our results suggest that
      the focal concerns that guide prosecutors' charging decisions incorporate
      specific victim behaviors and background characteristics.

PMID- 22455182
TI  - Predictors of victim-perpetrator relationship stability following a sexual
      assault: a brief report.
AB  - The researchers assessed the predictors of victim-perpetrator relationship
      stability following a sexual assault. Participants included 254 women sexually
      assaulted by a friend, casual dating partner, or steady dating partner. Results
      suggested that most victim-perpetrator relationships (75%) continued following
      the sexual assault. Greater trauma symptomatology, less perpetrator blame, and
      nondisclosure of the assault by victims predicted relationship continuation with
      the perpetrator. Additionally, the odds of continuing the relationship were
      greater following acts of sexual coercion than following acts of completed rape.
      Close relationships (steady dating partner) were more likely to continue
      following the sexual assault than less close relationships (friends and casual
      dating partners). Unexpectedly, the odds of relationship stability were greater
      for women without histories of childhood sexual abuse than women with histories
      of childhood sexual abuse. Implications for future research and intervention are
      discussed.

PMID- 22455183
TI  - Adapting dating violence prevention to francophone Switzerland: a story of intra
      western cultural differences.
AB  - Dating violence prevention programs, which originated in the United States, are
      beginning to be implemented elsewhere. This article presents the first adaptation
      of a violence prevention program for a European culture, Francophone Switzerland.
      A U.S. dating violence prevention program, Safe Dates (Foshee & Langwick, 1994),
      was reviewed in 19 youth and 4 professional focus groups. The most fundamental
      program concepts--"dating" and "violence"--are not the same in Switzerland and
      the United States. Swiss youth were not very focused on establishing monogamous
      romantic relationships, and there is no ready translation for "dating." Violence
      has not become the focus of a social movement in Switzerland to the same extent
      that it has in the United States, and distinctions among terms such as "dating
      violence" and "domestic violence" are not well known. Psychoeducational
      approaches are also less common in the Swiss context. As the movement to prevent
      violence extends worldwide, these issues need greater consideration.

PMID- 22455184
TI  - Epidemiology of mixed martial arts and youth violence in an ethnically diverse
      sample.
AB  - Mixed martial arts' (MMAs) growing international popularity has rekindled the
      discussion on the advantages (e.g., exercise) and disadvantages (e.g., possible
      injury) of contact sports. This study was the first of its kind to examine the
      psychosocial aspects of MMA and youth violence using an epidemiologic approach
      with an Asian American and Pacific Islander (AAPI) adolescent sample (N = 881).
      The results were consistent with the increased popularity of MMA with 52%
      (adolescent males = 73%, adolescent females = 39%) enjoying watching MMA and 24%
      (adolescent males = 39%, adolescent females = 13%) practicing professional fight
      moves with friends. Although statistically significant ethnic differences were
      found for the two MMA items on a bivariate level, these findings were not
      statistically significant when considering other variables in the model. The
      bivariate results revealed a cluster of risk-protective factors. Regarding the
      multiple regression findings, although enjoying watching MMA remained associated
      with positive attitudes toward violence and practicing fight moves remained
      associated with negative out-group orientation, the MMA items were not associated
      with unique variances of youth violence perpetration and victimization.
      Implications included the need for further research that includes other diverse
      samples, more comprehensive and objective MMA and violence measures, and
      observational and intervention longitudinal studies.

PMID- 22455185
TI  - Examining gender differences in the relationship between dating violence
      victimization and anger in college students.
AB  - It has been well established that dating violence victimization is associated
      with various mental health problems. Relatively, little is known about
      similarities and differences between mental health correlates of dating violence
      victimization for males and females. We examined the associations between
      physical and psychological victimization experiences and measures of anger in a
      sample of 200 male and female undergraduates. Results suggest that men's
      victimization was more strongly associated with different forms of anger than
      women's victimization.

PMID- 22455186
TI  - A prospective study of sexual assault and alcohol use among first-year college
      women.
AB  - This study prospectively examined the relation between alcohol use and sexual
      assault in a sample (N = 319) of first-year college women. Both frequency of
      drinking and frequency of binge drinking were measured. Over the course of their
      freshman year, 19.3% reported experiencing at least one sexual assault. Frequent
      binge drinking and frequent drinking predicted a subsequent sexual assault;
      however, experiencing a sexual assault did not predict changes in alcohol use.
      Frequent binge drinking demonstrated a stronger association with sexual assault
      than did frequent drinking. Findings help clarify the relation between alcohol
      use and sexual assault in college women and call for continued differentiation in
      assessment of alcohol use.

PMID- 22455187
TI  - The mental health focus in rape crisis services: tensions and recommendations.
AB  - In the evolution of rape crisis services, tensions persist between rape crisis
      service programs and mental health professionals. Changes within these programs
      and professions have brought the embedded concerns to the surface, but they
      remain unexamined and unresolved. Recent research on rape trauma and survivors'
      mental health needs has added to tensions by calling for description and
      evaluation of rape crisis services and timely psychological treatment for
      survivors. This article offers a new perspective by discussing the tensions in an
      open but balanced way so as to promote discussion and solutions. Recommendations
      and action steps are offered for promoting constructive dialogue and change to
      improve direct services for survivors.

PMID- 22455189
TI  - Suicide clusters: introducing a novel type of categorization.
AB  - A suicide cluster within a given community may be defined as a group of suicides
      or suicide attempts, or both, that happen closer together in time and space than
      would generally be expected. However, since the perception of clustering may
      itself be a risk factor for suicide, suicide clusters differ almost from all
      other event clusters. The aim of this article, therefore, is to discuss the
      unique pattern of suicide cluster and introduce a novel type of categorization
      taking into account varieties of studies, which investigate suicide clusters
      within diverse settings. This article concludes with challenging areas in suicide
      cluster studies and emphasizing that each community must deal rapidly and
      appropriately with any perceived suicide clusters.

PMID- 22455188
TI  - Physical victimization of rural methamphetamine and cocaine users.
AB  - Substance use and physical violence often coincide, but little has been published
      on the correlates associated with receipt of partner versus nonpartner physical
      violence for rural users of methamphetamine and/or cocaine. In this study,
      participants' substance use, depression and past-year physical victimization were
      assessed. In separate logistic regression models, received partner violence in
      females was associated with age; alcohol, cocaine, and methamphetamine
      abuse/dependence; and number of drugs used in the past 6 months. In males,
      received nonpartner violence was associated with age, cocaine abuse/dependence,
      and being Caucasian. Findings suggest a relationship between stimulant use and
      received violence among rural substance users and a need for victimization
      screenings in settings where such individuals seek health care.

PMID- 22455190
TI  - Fractionated care.

PMID- 22455191
TI  - Supervision of physician assistants and nurses.

PMID- 22455192
TI  - Step 1: preparation. Getting started on the road to health information
      technology.

PMID- 22455193
TI  - Uncertain marketplace holds opportunities for Michigan physicians.

PMID- 22455194
TI  - ACOs under construction--one part integration, one part, coopetition.

PMID- 22455195
TI  - A tragic lesson in drug safety.

PMID- 22455196
TI  - Who are the new leaders of health care? All of us.

PMID- 22455198
TI  - Practicing: the reader's issue: Introduction.

PMID- 22455197
TI  - Let's take our profession back!

PMID- 22455199
TI  - Complex environment--difficult practice choices.

PMID- 22455200
TI  - Idiopathic.

PMID- 22455201
TI  - Life can unexpectedly change in a moment!

PMID- 22455202
TI  - The cost of treating cancer patients: treatments versus reimbursements.

PMID- 22455203
TI  - Psychiatric diagnoses in a managed care environment: taking time for the patient.

PMID- 22455204
TI  - Health care reform = quality?

PMID- 22455205
TI  - Finding my dream job!

PMID- 22455206
TI  - Finding inspiration in the VA Health Care System.

PMID- 22455207
TI  - Training the trainers to help students become good physicians.

PMID- 22455208
TI  - I love the team-based practice.

PMID- 22455209
TI  - My life of practicing medicine.

PMID- 22455210
TI  - A full life as an academician.

PMID- 22455211
TI  - Keeping Kaiser medicine in the family.

PMID- 22455212
TI  - The joy of personal patient interactions.

PMID- 22455213
TI  - There is still so much work to do.

PMID- 22455214
TI  - MedChi to focus on public health and public safety in 2012 session.

PMID- 22455215
TI  - Dispose of your medicine safely and say "no" to bullying.

PMID- 22455216
TI  - University of Maryland School of Medicine increases medical student education in
      primary care.
AB  - In August 2012 the University of Maryland School of Medicine will start a new
      Primary Care Track for incoming first year medical students as a collaborative
      program of the departments of Family and Community Medicine, Internal Medicine,
      and Pediatrics. Its focus will be to introduce all students to primary care role
      models early in medical school, and to offer a longitudinal experience in primary
      care in rural and urban underserved communities to interested students, with the
      intention of increasing the number of UMD medical students who choose primary
      care careers in these communities.

PMID- 22455217
TI  - Words and symbols.

PMID- 22455218
TI  - Downbanding nurses is a false economy.

PMID- 22455219
TI  - NMC set to gain new powers in review of regulatory framework.

PMID- 22455220
TI  - Trust accused of ignoring staff concerns over personal safety.

PMID- 22455221
TI  - Safe staffing levels and CPD are top of unions' wish list in pay talks.

PMID- 22455222
TI  - RCN congress will debate effects of adult video games on children.

PMID- 22455223
TI  - An ever-increasing workload is causing burnout and exhaustion.

PMID- 22455224
TI  - A source of comfort.
AB  - Recent statistics from the Patients Association show 17 per cent of patients
      raised poor pain relief as a concern in calls to its helpline. In the third of
      our four-part series examining the four strands of fundamental care, we look at
      how competing demands can affect effective pain relief and how some organisations
      have made improvements.

PMID- 22455225
TI  - 'Would you like to help quit'?
AB  - Despite a steep fall in smoking rates, tobacco use is still a major cause of non
      communicable diseases, responsible in the U.K. for one in five of all cancers.
      Globally and in the U.K., poorer people are most at risk. However, NHS cessation
      services are effective. Nurses should be prepared to ask patients about smoking,
      and be explicit about the damage it causes.

PMID- 22455226
TI  - The effect of body image and mood on smoking cessation in women.
AB  - This article focuses on how nurses can encourage successful smoking cessation in
      women. Emphasis is placed on the effect of body image and mood on quitting and
      how knowledge of these barriers can equip nurses to provide appropriate support.

PMID- 22455227
TI  - Management of bladder dysfunction in patients with multiple sclerosis.
AB  - Multiple sclerosis is a chronic disease of the central nervous system that often
      has a disabling effect, resulting in reduced quality of life for patients.
      Bladder dysfunction is a common and distressing symptom. Nurses can have a key
      role in the management of this symptom by promoting an integrated approach to
      care, thereby improving bladder control and reducing patient anxiety. This
      article explores the core elements of a specialist continence assessment in this
      patient group, and provides a critical overview of treatments used for managing
      bladder problems.

PMID- 22455228
TI  - Chronic fatigue syndrome or myalgic encephalomyelitis.
AB  - Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a debilitating
      illness that affects many systems of the body, particularly the nervous and
      immune systems. The condition affects all age, racial, ethnic and socioeconomic
      groups. This article focuses on the knowledge, understanding and skills necessary
      to recognise, assess, manage and support patients with CFS/ME. The principles of
      management and rehabilitation can be applied by nurses and other healthcare
      professionals irrespective of the clinical setting and context.

PMID- 22455229
TI  - Vascular access devices.

PMID- 22455230
TI  - Stay on course during change.

PMID- 22455231
TI  - On a fact-finding mission.

PMID- 22455232
TI  - Take a different path.

PMID- 22455233
TI  - Erasures and suspensions from the General Medical Council (U.K.).

PMID- 22455234
TI  - Is antenatal screening for syphilis still necessary?

PMID- 22455235
TI  - An update on the economics of dementia care in Ireland.

PMID- 22455236
TI  - Effectiveness of 2010/2011 seasonal influenza vaccine in Ireland.
AB  - We conducted a case-control study to estimate the 2010/2011 trivalent influenza
      vaccine effectiveness (TIVE) using the Irish general practitioners' influenza
      sentinel surveillance scheme. Cases were influenza-like illness (ILI) patients
      with laboratory-confirmed influenza. Controls were ILI patients who tested
      negative for influenza. Participating sentinel general practitioners (GP)
      collected swabs from patients presenting with ILI along with their vaccination
      history and other individual characteristics. The TIVE was computed as (1 - odds
      ratiofor vaccination) x100%. Of 60 sentinel GP practices, 22 expressed interest
      in participating in the study and 17 (28%) recruited at least one ILI patient. In
      the analysis, we included 106 cases and 85 controls. Seven controls (8.2%) and
      one influenza case (0.9%) had been vaccinated in 2010/2011. The estimated TIVE
      against any influenza subtype was 89.4% [95% CI: 13.8; 99.8%], suggesting a
      protective effect against GP-attended laboratory confirmed influenza. This study
      design could be used to monitor influenza vaccine effectiveness annually but
      sample size and vaccination coverage should be increased to obtain precise and
      adjusted estimates.

PMID- 22455237
TI  - Parenteral nutrition in very low birth weight infants in the United Kingdom and
      Ireland.
AB  - Parenteral nutrition (PN) plays an important role in providing nutrients for
      infants unable to tolerate enteral feeds study was to look at PN prescribing in
      neonatal units in the United Kingdom (U.K.) and Ireland, in particular in infants
      < 1.5 kg. A postal questionnaire was administered to the 235 neonatal units. The
      response rate was 179 (76%), of which 136 (76%) used PN. The initial amount of
      protein prescribed was 0.1-2 g/kg/day in 102 units (91%), >2 g/kg/day in 4 (4%)
      and 5 (5%) used no protein. 88 (80%) started lipids with the first PN
      prescription. Only 5 units (5%) started with >1 g/kg/day. The maximum dose of
      lipids and protein both varied from 2 - >4 g/kg/day. The initial glucose infusion
      rate was 4-8 mg/kg/min. Interestingly only 44% of units started PN in the first
      24 hours of age. Hence results show great variation in PN prescribing.

PMID- 22455238
TI  - A computer based, automated analysis of process and outcomes of diabetic care in
      23 GP practices.
AB  - The predicted prevalence of diabetes in Ireland by 2015 is 190,000. Structured
      diabetes care in general practice has outcomes equivalent to secondary care and
      good diabetes care has been shown to be associated with the use of electronic
      healthcare records (EHRs). This automated analysis of EHRs in 23 practices took
      10 minutes per practice compared with 15 hours per practice for manual searches.
      Data was extracted for 1901 type II diabetics. There was valid data for >80% of
      patients for 6 of the 9 key indicators in the previous year. 543 (34%) had a
      Hba1c > 7.5%, 142 (9%) had a total cholesterol >6 mmol/l, 83 (6%) had an LDL
      cholesterol >4 mmol/l, 367 (22%) had Triglycerides > 2.2 mmol/l and 162 (10%) had
      Blood Pressure > 160/100 mmHg. Data quality and key indicators of care compare
      well with manual audits in Ireland and the U.K. electronic healthcare records and
      automated audits should be a feature of all chronic disease management programs.

PMID- 22455239
TI  - Survival in women with ovarian cancer before and after the introduction of
      adjuvant paclitaxel; a 25-year, single institution review.
AB  - Adjuvant chemotherapy regime for ovarian cancer patients remains to be a
      contentious issue. The aim of this study was to compare the overall and
      progression-free survival of women with ovarian cancer before and after
      introduction of paclitaxel in our unit in 1992. A sample of 112 women who
      received adjuvant therapy following surgery for ovarian cancer was collected, 68
      (61%) received platinum+alkylating agent before 1992 and later 44 (39%) received
      platinum+paclitaxel. Five-year survival was same in both treatment groups when
      there was no macroscopic disease after surgery (78% versus 70%) and when residual
      disease was <2 cm (50% versus 40%). Survival was greater in women with residual
      disease >2 cm in the platinum+paclitaxel group (50% versus 24%), (p = 0.04).
      However, progression-free survival was similar in both groups irrespective of
      stage or residual volume of disease. Therefore consideration to selective use of
      paclitaxel could reduce patient morbidity and costs significantly.

PMID- 22455240
TI  - The use of computerised tomography guided percutaneous fine needle aspiration in
      the evaluation of solitary pulmonary nodules.
AB  - The evaluation of a solitary pulmonary nodule (SPN) has changed over the years
      with increased access to percutaneous computerised tomography (CT) guided fine
      needle aspiration (FNA), where bronchoscopy is unhelpful. The aim of our study
      was to evaluate the sample adequacy, diagnostic and complication rate of CT-FNA
      of a SPN at our academic teaching hospital over an 18 month period. CT-FNA was
      performed by a radiologist, with a cytopathologist in attendance to confirm the
      adequacy of the sample obtained. The size of the nodule, sample material and
      adequacy, diagnosis and complications were recorded. A total of 101 patients were
      included, 54 male and the mean age was 68 +/- 11 years. The mean size of the SPN
      was 2.3 cm (range 1-11 cm). 56 (56%) patients had a right SPN, 45 (45%) had a
      left SPN. CT-FNA was diagnostic in 80 (80%) patients and non-diagnostic in 21
      (20%) patients. The sample was insufficient for immunocytochemistry, although the
      morphological appearance was diagnostic in 20 (25%) of the 80 patients.
      Pneumothorax occurred in 26/101 (26%) patients post CT-FNA, of these 7 (27%)
      required chest drain insertion, while 19 (73%) were managed conservatively. CT
      FNA is a useful tool for the diagnosis of a SPN, with our diagnostic accuracy
      comparable to that reported in the literature. However, CT-FNA may not provide
      adequate sample volume to perform ancillary testing and has a moderate
      complication rate.

PMID- 22455241
TI  - Is it important to classify ischaemic stroke?
AB  - Thirty-five percent of all ischemic events remain classified as cryptogenic. This
      study was conducted to ascertain the accuracy of diagnosis of ischaemic stroke
      based on information given in the medical notes. It was tested by applying the
      clinical information to the (TOAST) criteria. Hundred and five patients presented
      with acute stroke between Jan-Jun 2007. Data was collected on 90 patients. Male
      to female ratio was 39:51 with age range of 47-93 years. Sixty (67%) patients had
      total/partial anterior circulation stroke; 5 (5.6%) had a lacunar stroke and in
      25 (28%) the mechanism of stroke could not be identified. Four (4.4%) patients
      with small vessel disease were anticoagulated; 5 (5.6%) with atrial fibrillation
      received antiplatelet therapy and 2 (2.2%) patients with atrial fibrillation
      underwent CEA. This study revealed deficiencies in the clinical assessment of
      patients and treatment was not tailored to the mechanism of stroke in some
      patients.

PMID- 22455242
TI  - Assessment of paediatric clinical audit.
AB  - Consultant paediatricians in Ireland were surveyed to evaluate their perceptions
      of the hospital audit environment and assess their involvement in the audit
      process. Eighty nine (77%) replied of whom 66 (74%) had an audit department and
      23 (26%) did not. Sixteen (18%) felt their hospital was well resourced for audit
      and 25 (28%) felt the culture was very positive but only 1 (1%) had protected
      time. For 61 (69%) consultants audit was very important with 38 (43%) being very
      actively involved in the process. The most frequent trigger for audit was non
      consultant hospital doctor (NCHD) career development, cited by 77 (87%). The new
      Professional Competence Scheme and the National Quality and Risk Management
      Standards will require the deficiencies identified in this survey be addressed.

PMID- 22455243
TI  - Thromboprophylaxis for women undergoing caesarean section.
AB  - Thromboprophylaxis for women undergoing caesarean section (CS) was introduced in
      the hospital in 1995. This study audited the use of tinzaparin prophylaxis in a
      nested cohort of women who screened negative for diabetes mellitus at 28 weeks
      gestation. All the women had their weight measured and BMI calculated at the
      first antenatal visit. Of the 284 women, 68 (24%) had a CS and all received
      tinzaparin. Of the 68, however, 94% received a dose lower than recommended.
      Compliance with prophylaxis was complete but compliance with the recommended
      dosage was suboptimal, which may result in venous thromboembolism after CS
      despite thromboprophylaxis.

PMID- 22455244
TI  - The role of a movement disorders clinic.
AB  - Ireland's ageing population will result in a substantial increase in
      neurodegenerative disease with a projected increase in prevalence of Idiopathic
      Parkinson's disease (IPD) to 9,000 by 2021. There are few published audits of
      neurology services to assist care planning. As a first step towards evaluating
      future service needs for this group of patients, we audited a single tertiary
      referral IPD and Other Movement Disorders clinic for 2006. A total of 497
      patients from all counties in Ireland were seen; 225 (59%) of patients had IPD,
      32 (8.2%) had atypical parkinsonism, and 22 (5.8%) dystonia. In a subset of 275
      patients, 151 (55%) were referred by GPs, 74 (27%) by other consultants, and 49
      (18%) by other consultant neurologists. Diagnosis was changed in 22 (38%) and
      medication was adjusted in 203 (74%). A telephone survey of 50 patients
      demonstrated 100% satisfaction with the improved access to the clinical nurse
      specialist, telephone support and improved continuity of care. The IPD and Other
      Movement Disorders clinic provides an important local, regional, and national
      diagnostic and therapeutic service for complex movement disorders. It is proposed
      that a national registry of IPD and audit of the delivery of care to patients
      with movement disorders is needed.

PMID- 22455246
TI  - Fibromyalgia, is it a true rheumatological or a psychogenic condition?

PMID- 22455245
TI  - Morning report: a recommendation to improve medical handover.

PMID- 22455247
TI  - Implementation of the primary care strategy 2005: a study of the experiences of
      team work among members of primary care teams in County Wexford in 2011.

PMID- 22455248
TI  - Research ethics need consideration.

PMID- 22455249
TI  - Troponin-I positivity in patients referred to Rapid Access Chest Pain Clinic.
AB  - BACKGROUND: Rapid Access Chest Pain Clinics (RACPCs) are set up to access
      patients with new onset chest pain (within the preceding three weeks), of
      possible cardiac origin. These patients are seen in the clinic within two weeks
      of referral and the attending physician takes a history, performs a routine
      clinical examination, and if clinically justified, a treadmill exercise test is
      performed according to Bruce Protocol. Within the group of patients referred to
      the RACPC with new onset but otherwise stable angina, there is a potential
      overlap with patients who in fact may have an evolving acute coronary syndrome,
      i.e., unstable angina. The aim of this study was to assess the prevalence of
      Troponin-I positivity as an indicator of acute coronary syndrome. METHODS: This
      cross-sectional descriptive study included 60 consecutive patients referred to
      the RACPC with history of recent onset chest pain (within the last three weeks)
      of possible cardiac origin and positive ETT or confirmed abnormal ischemic ECG at
      baseline. Troponin-L was measured in these patients. RESULTS: Out of the total 60
      patients, 8.33% of the patients referred to RACPC with new onset angina had
      positive cTnI. CONCLUSION: Point of care test (POCT) for cTnI can help to
      identify the high risk patient referred to RACPC.

PMID- 22455251
TI  - Diagnostic accuracy of magnetic resonance imaging in meniscal injuries of knee
      joint and its role in selection of patients for arthroscopy.
AB  - BACKGROUND: Magnetic Resonance Imaging (MRI) is frequently advised to evaluate
      clinically suspected cases of meniscal injuries in our setup. The objective was
      to determine the diagnostic accuracy of MRI in meniscal injuries of knee joint
      and its effectiveness in selection of patients for arthroscopy. METHODS: A Cross
      sectional comparative study was conducted at Radiology Department Military
      Hospital (MH) Rawalpindi in collaboration with Orthopaedic Department Combined
      Military Hospital (CMH) Rawalpindi from 31 Jan 2007 to 1 Aug 2007. Fifty-seven
      patients with clinical suspicion of meniscal injuries were subjected to MRI.
      Arthroscopy was done only in 34 patients while 23 were excluded on the basis of
      MRI findings. MRI findings were compared with arthroscopic findings. Medial and
      lateral menisci were considered separately in each case. RESULTS: Among 57
      patients only 30 showed significant tear on MRI. Arthroscopy was done in these
      cases. Arthroscopy was considered on clinical grounds only in 4 patients who did
      not show significant tear on MRI. MRI showed Medial Meniscus (MM) injury in 23
      patients and Lateral Meniscus (LM) injury in 10 patients. Arthroscopy confirmed
      MM injury in 17 patients and LM injury in 7 patients. MRI missed two MM and one
      LM injuries. This showed that MRI has sensitivity of 89.4% and specificity of 62%
      in diagnosing injuries of MM, while sensitivity of 87% and specificity of 88% in
      diagnosing injuries of LM. Diagnostic accuracy of MRI in MM and LM injuries was
      76.4% and 88.2% respectively. CONCLUSION: MRI is accurate in diagnosing meniscal
      injuries of knee joint and is effective in selection of patients for arthroscopy.

PMID- 22455250
TI  - Frequency of depression and somatic symptoms in patients on interferon
      alpha/ribavirin for chronic hepatitis C.
AB  - BACKGROUND: Large numbers of patients suffering from Chronic Hepatitis C (HCV)
      are seeking treatment with interferon alpha (IFN) because of significant advances
      in overall improvement in the course of HCV and its complications. Objectives
      were to estimate the frequency of depression and somatic symptoms in patients on
      interferon alpha/ribavirin treatment for chronic hepatitis C. METHODS: It was an
      observational study conducted in the out-patient Department of Gastroenterology
      Shaikh Zayed Hospital, Lahore during a period of three months, i.e., from
      September to November 2008. One hundred consecutive patients undergoing
      interferon alpha/ ribavirin treatment for chronic HCV were included in the study.
      All patients, irrespective of age, sex or duration of treatment were administered
      with a check list of common physical complaints and DSM-IV symptoms for Major
      Depressive Episode. RESULTS: Out of a total of 100 subjects 37 were male and 63
      were female. In all, 39 (39%) patients fulfilled the diagnostic criteria of DSM
      IV for Major Depressive Episode. Major Depression was more common in female 28
      (44.4%) as compared to male 11 (28.7%) patients. Somatic symptoms were common in
      all the patients but they were reported more frequently by patients with Major
      Depression compared to those without Major Depression. Myalgias, headache, joint
      pain, nausea/vomiting, abdominal pain and palpitation were the most common
      physical symptoms. CONCLUSION: Major Depression and somatic complaints are a
      common consequence of interferon alpha/ribavirin treatment for chronic hepatitis
      C. All patients receiving this treatment should be periodically assessed for the
      detection of these side effects to promptly address relevant treatment options.

PMID- 22455252
TI  - Impact of socioeconomic factors on nutritional status in primary school children.
AB  - BACKGROUND: Child malnutrition is a major public health and development concern
      in most of the poor communities leading to high morbidity and mortality. Various
      studies have highlighted the factors involved. The present study focuses on
      socioeconomic inequality resulting in malnutrition. Objectives of the Study were
      to find the Impact of socio-economic factors on nutritional status in primary
      school children. METHODS: It was a cross sectional survey conducted at Lahore
      from February to August 2005 among primary schools from public and private
      sectors to assess the nutritional status of primary school going children age 5
      11 years belonging to different socio economic classes of the society. Systematic
      random sampling technique was applied to collect the sample. Body Mass Index in
      relation to NHANES reference population was used for assessing nutritional
      status. RESULTS: The nutritional status of children from lower socio economic
      class was poor as compared to their counter parts in upper socio economic class.
      Children with BMI < 5th percentile were 41% in lower class while in upper class
      it was 19.28%. Prevalence of malnutrition was 42.3% among children of illiterate
      mothers as compare to 20% in those of literate mothers. CONCLUSION: Poverty, low
      literacy rate, large families, food insecurity, food safety, women's education
      appears to be the important underlying factors responsible for poor health status
      of children from low socioeconomic class. It requires economic, political and
      social changes as well as changes for personal advancement mainly through
      educational opportunities to improve the nutritional status of the children.

PMID- 22455253
TI  - Frequency of severe mitral stenosis in young female patients having pure mitral
      stenosis secondary to rheumatic heart disease.
AB  - BACKGROUND: High morbidity and mortality due to Rheumatic heart disease (RHD)
      associated with females is mainly because of late diagnosis on one hand and
      socioeconomic reasons on the other hand. Poor referral to tertiary care centres
      leads to delayed diagnosis which results in complications. The objectives of this
      cross-sectional descriptive study was to assess the frequency of severe mitral
      stenosis in woman of child bearing age, having pure mitral stenosis (MS)
      secondary to rheumatic heart disease. METHODS: Two hundred and fifty women of
      child bearing age with RHD were enrolled in the study using consecutive non
      probability sampling technique. Out of these 250 patients, cases of pure MS were
      selected. Patients with associated mitral regurgitation and aortic valve disease
      were excluded. After admission, assessment of mitral valve stenosis was done with
      2D colour Doppler echocardiography. RESULTS: Out of 250 consecutive patients of
      rheumatic carditis, 110 (44%) patients had pure mitral valve stenosis, 85 (34%)
      had stenosis with mitral regurgitation and 55 (22%) patients had both mitral and
      aortic valve problem of varying severity. Among 110 patients with pure mitral
      valve stenosis, 48 (43.6%) had severe mitral valve stenosis. Severe mitral valve
      gradient (MVG) and high pulmonary artery pressure (PAP) was observed in 66 (60%)
      and 49 (44.5%) of the patients respectively. CONCLUSION: This high frequency can
      be linked to lack of early detection of the disease at primary level, poor
      management of throat infections and poor rheumatic fever prophylaxis at community
      level.

PMID- 22455254
TI  - Is nasogastric decompression necessary in elective enteric anastomosis?
AB  - BACKGROUND: Placement of nasogastric tube is common surgical practice after bowel
      anastomosis. What is to be achieved by this prophylaxis is gastric decompression,
      a decreased likelihood of nausea and vomiting, decreased distension, less chance
      of pulmonary aspiration and pneumonia, less risk of wound separation and
      infection, less chance of fascial dehiscence and hernia, earlier return of bowel
      function and earlier discharge from hospital. We conducted a prospective
      observational study in Surgical Ward 2, Jinnah Postgraduate Medical Centre,
      Karachi from January 2008 to December 2009 to assess whether routine use of
      nasogastric decompression in elective enteric anastomosis can be safely omitted.
      METHOD: Patients who underwent elective enteric anastomosis were included in this
      study. These patients were managed prospectively without nasogastric
      decompression. Outcome were measured in terms of time of passing flatus, nausea,
      vomiting, abdominal distension, pulmonary complications, wound infection, wound
      dehiscence, anastomotic leak, length of hospital stay and mortality. RESULTS:
      Except for incidence of minor symptoms like nausea or vomiting, omission of NG
      tube did not lead to any serious complication like anastomotic leak, pulmonary
      complications wound dehiscence or death. CONCLUSION: Nasogastric decompression
      can safely be omitted from a routine part of postoperative care after elective
      enteric anastomosis.

PMID- 22455255
TI  - Prevalence of obesity among the school-going children of Lahore and associated
      factors.
AB  - OBJECTIVE: To determine the prevalence of obesity among the school- going
      children (6th and 7th grade) of Lahore and ascertain the associated factors.
      METHOD: A descriptive study with sample size of 293 children conducted over a
      period of four months in two private sector schools of Lahore. Information was
      gathered by the help of a pre designed questionnaire after getting formal consent
      from parents. Children included in the study were healthy with no reported
      chronic illness. Body weight was measured in minimal clothing using a weight
      scale; body height was measured in erect posture without shoes using a
      stadiometer. Obesity, underweight and overweight were defined by plotting BMI
      against age (in months and years) on WHO BMI-for-age (5-19 years [percentiles])
      charts. RESULTS: Out of 293 children 11.9% were obese (more than 97th percentile)
      while 21.8% were overweight (85th-97th percentile). Among obese children 74.3%
      were found to watch TV for 1-2 hours daily while 25.7% watch TV for 3-4 hours.
      48.6% of obese children did not participate in any field sports while 34.3% have
      less than 3 hours participation in field sports. Among parents of obese children,
      60% were found to have little or no influence on their children's food intake at
      school whereas 22.9% parents of obese children never advise them against eating
      junk food. Parents think that ban on advertisements promoting unhealthy foods
      (75.1%) and use of popular media characters in promoting healthy foods (83.6%)
      and exercise can help in preventing obesity in children. CONCLUSION: This study
      shows that high prevalence of obesity and overweight among children in private
      schools has direct relationship with decreased physical activity and other
      factors like watching TV, role of media and lack of diet control by parents.

PMID- 22455256
TI  - Neonatal sepsis: causative bacteria and their resistance to antibiotics.
AB  - BACKGROUND: Neonatal sepsis is one of the major causes of neonatal morbidity and
      mortality, particularly in developing countries. The objective of this study was
      to determine the causative bacteria and level of their resistance to commonly
      used antibiotics. METHODS: This descriptive study was carried out at Ayub
      Teaching Hospital, Abbottabad from April 2009 to January 2010. All neonates of
      either gender admitted in neonatology unit with clinical sepsis and positive
      blood culture were included in the study. Neonatal period was defined as 28 days
      of life at term and up to 44 weeks of gestational age in preterm babies. One
      hundred and thirty neonates of either gender were studied during the period.
      Blood sample for culture was taken from a peripheral vein or an artery ensuring
      standard anti-septic measures. BACTEC technique was used for obtaining bacterial
      growth and drug sensitivity after incubation of 24-48 hours. Second blood culture
      was also performed in few cases which were not showing improvement after initial
      treatment. RESULTS: Male to female ratio was 1.3:1. Early and late onset sepsis
      was found in 29.2% and 70.8% respectively. Gram-negative bacteria were more
      frequent than gram-positive bacteria with a frequency of 54.6% and 45.4%
      respectively. Gram-positive and gram-negative bacteria showed high resistance
      against commonly used antibiotics such as ampicillin, amoxicillin, cefotaxime,
      ceftriazone and gentamicin. CONCLUSION: Staph. aureus is the most common gram
      positive bacterium and E. coli is the most common gram-negative bacterium causing
      neonatal sepsis. Gram-positive and gram-negative bacteria are highly resistant
      against commonly used antibiotics such as ampicillin, amoxicillin, cefotaxime,
      ceftriazone and gentamicin, and are relatively more sensitive to less commonly
      used drugs like amikacin and ceftazidime.

PMID- 22455257
TI  - Feasibility of early surgical intervention in postoperative entero-cutaneous
      fistulae.
AB  - OBJECTIVES: To study the out come and benefits of an early surgical intervention
      in postoperative entero-cutaneous fistulae. METHODS: It's a retrospective
      descriptive study conducted at department of surgery LUMHS from Jan 2001 to
      November 2008. Two hundred and thirteen (213) post-operative fistulae are
      included as study subjects while those due to inflammatory bowel diseases, road
      traffic accidents or following blunt, stab or gunshot abdominal trauma are
      excluded. An aggressive treatment to build up nutritional status, correction of
      anaemia and control of sepsis was followed by surgical intervention as soon as
      the patient's condition permitted. Variables such as type of fistula, out put per
      24 hours, duration since development, complications due to fistula, nutritional
      status, operative procedure, operative time, post-operative complications, total
      post-operative stay, follow up schedule, outcome. The results were statistically
      analysed on SPSS-12. RESULTS: A total 213 patients comprising 184 males (85.6%)
      and 29 (13.5%) females with a mean age of 36.08 years and a range of 64 (78-14)
      years presenting with post-operative enter-cutaneous fistula are included in the
      study. Maximum number of patients (171, 79.5%) developed fistula between 4th-6th
      postoperative day and a vast majority of fistula occurred in the ileum (207,
      97.18%) either as a result of anastomotic failure (103), leak from primary
      closure (99) or from un-noticed missed perforations (5). Of the total number, 24
      patients eventually died making a mortality of 11.2%. Early surgical intervention
      proved life saving (p < 0.001). A strong relation was found pre-operative albumin
      levels and surgical closure of the fistula (p < 0.001) and associated mortality
      (p < 0.001). CONCLUSION: High out put fistula is unlikely to close spontaneously
      on conservative measures. Early surgical intervention can be life saving.

PMID- 22455258
TI  - Relationship of selected prenatal factors to pregnancy outcome and congenital
      anomalies.
AB  - OBJECTIVE: The aim of this paper is to explore the relationship of various
      selected prenatal circumstances to pregnancy outcome in particular reference to
      congenital anomalies. METHOD: It was a cross-sectional analytical study and
      conducted at unit 'A' of the Department of Obs/Gyn, Postgraduate Medical
      Institute, Lady Reading Hospital, Peshawar, from January to December 2009. The
      analysis included data on all women having pregnancies with adverse outcome and
      various congenital anomalies during the study period 1st January to 31st December
      2009. A hospital-based maternal health data was used from history records and
      direct interviewing of the patients subject to their availability and information
      were recorded for all the cases on structured proformae. The data included
      demographic details, social environment, consanguinity, ovulation induction, drug
      intake during early pregnancy, exposure to radiation, infection during early
      pregnancy, complications of pregnancy, prematurity, obstetrical variables,
      congenital anomalies and materno-foetal morbidity and mortality. Findings at
      prenatal visits and data regarding prior pregnancies and morbidity among other
      children are also abstracted from obstetrical and medical charts. In case of the
      newborn, the neonatal chart abstract has proved to be a more complete source of
      information on congenital anomalies. The data was entered on SPSS-10 and the
      analysis included simple proportions and rates. RESULTS: Out of a total of 5,082
      deliveries 163 (3.2%) were complicated by various congenital anomalies with
      prepondrence of neural tube defects notably the hydrocephalous (33.4%) and
      Anencephaly (29.2%). Most of the mothers were un-booked and uneducated (90%).
      Eighty-eight (54%) women were in there twenties, thirty (22%) with > or = 35
      years of age and only 9%in the teenage group. About 36% of the deliveries in the
      study population are among primigravida. Four cases (3.1%) had history of
      exposure to some non-specific radiation due to the locality of there house.
      Almost 21% of couples had cousin marriage. Regarding drug intake no specific link
      could be demonstrated as 45% took nothing while the remaining took the
      multivitamins and tonics only. Only 4 cases (2.5%) had taken assisted conception
      in the form of clomiphene citrate. About 34 per cent of the multigravida with
      antepartum bleeding reported that their last prior pregnancy ended in a foetal
      death or prematurely born infant. The corresponding figure for all multigravida
      women was 21 per cent. However, prior pregnancy history does not explain the more
      adverse risk associated with APB. CONCLUSION: These results together provide
      information to physicians and genetic counsellors to realise contribution of
      congenital abnormalities and setting priorities of screening individual cases.

PMID- 22455259
TI  - Evaluation of modified Alvarado score for frequency of negative appendicectomies.
AB  - BACKGROUND: Appendicitis being the commonest surgical emergency is primarily
      diagnosed clinically but posses diagnostic difficulty usually, especially to
      junior surgeons, demanding the need for tool/scoring system that can be easily
      applicable, accurate & reproducible in the diagnosis of appendicitis, with low
      negative Appendicectomy rate. This study is designed to assess one such scoring
      system, i.e., Modified Alvarado Score. METHODS: A total of 100 consecutive male
      and female patients with age 10 year and above presenting with symptoms
      suggestive of acute appendicitis were included in study, assessed according to
      eight variables of Modified Alvarado scoring system and were accordingly placed
      into 3 groups. Group-I patients having score 1-4 were discharged, Group-II
      patients having score 5-7 were observed while Group-III patients having score 8
      10 were operated. Status of appendix of operated patients was assessed histo
      pathologically. RESULTS: Out of 100 patients included in study, 58 patients were
      operated on the basis of said scoring system. Of the operated patients 52
      (89.65%) had acute appendicitis, thus yielding a positive predictive value of
      89.66% while negative appendectomy rate of 10.34%. Frequency of negative
      appendicectomy was 7.69% (3/39) amongst males and 15.79% (3/19) in females. Post
      operative complication rate including wound infection, pelvic abscess, chest and
      urinary tract infection was 22.41% (13/58). CONCLUSION: Frequency of the negative
      appendicectomies can be reduced through standardization of the diagnostic
      procedure, by applying Modified Alvarado score in the diagnosis of suspected
      appendicitis cases as compared to simple clinical assessment.

PMID- 22455260
TI  - Prevalence of obesity in school children of Hazara division.
AB  - BACKGROUND: Limited data is available in Pakistan regarding prevalence of obesity
      in school going children. The objective of this study was to find out obesity
      prevalence in school going children in Hazara division. METHODS: It was
      descriptive study. Data of 3200 students was collected over six month period,
      from Hazara Division. Four schools were selected in each district two for boys
      and two for females. District Kohistan was excluded from study as female
      education is not permitted beyond primary education. Children 5-14 year age group
      were included in the study. Initial 20 students of each class were selected for
      study. Anthropometric data (weight, height) for each student was collected and
      entered on Performa structured for this purpose. BMI was calculated and values
      were compared with standard BMI charts of National Health Centre for health
      statistics. RESULTS: Prevalence of obesity was 4.78%. Out of 3,200 children
      enrolled 153 (4.78%) were obese. Male to female ratio was 1:1.2. The prevalence
      of obesity was high in private school students than government schools (66.66%
      and 33%). The prevalence was high in both sexes in 12-14 years and 6-7 years age
      groups (49% and 20.26%). CONCLUSION: Prevalence of obesity in present study is
      similar to the results from developing countries in the region but prevalence is
      lower than developed countries. Problem of obesity also exists in developing
      countries and there is need to create awareness about obesity and related
      complications.

PMID- 22455261
TI  - Alpha-1 microglobulin: a marker for early detection of tubular disorders in
      diabetic nephropathy.
AB  - BACKGROUND: Tubular damage as suggested by tubular proteinuria is a recognised
      feature of glomerulonephritis. The objectives of the study were to compare the
      level of alpha-microglobulin in normal and diabetic patients, and also to find
      out whether the level of alpha-1 microglobulin could become a laboratory marker
      for tubulo-interstitial damage in diabetic nephropathy. METHODS: Twenty-nine
      registered Type II diabetic patients of either sex were studied. The patients'
      age ranged from 41-50 years who were admitted in the medical ward, and those who
      visited the outdoor department of Sir Ganga Ram Hospital, Lahore were included in
      the study. The duration of study was one year from June 2006 to June 2007. Ten
      normal subjects with no history of diabetes were taken as controls. Blood samples
      and 24 hour urine samples of patients of all groups were collected. The levels of
      urinary protein and blood sugar were estimated by auto analyser. Proteinuria
      positive urinary samples were analysed by SDS-PAGE electrophoresis. RESULTS: The
      level of alpha-1 urinary protein was significantly increased in the group of
      diabetic patients as compared to the urinary protein level of normal subjects.
      Blood sugar level was also significantly increased in patients as compared to
      controls. Level of low molecular weight protein alpha-1 microglobulin showed an
      electrophoresis band of 28 Kda with an average volume of 6741.88 in the urine
      sample of patients. On the other hand, a very light, hardly recognisable band was
      observed in normal subjects. CONCLUSION: Urinary alpha-1 microglobulin provides a
      noninvasive and inexpensive diagnostic alternative for the diagnosis and
      monitoring of urinary tract disorders, i.e., early detection of tubular disorders
      of diabetic nephropathy. We propose that SDS-PAGE electrophoresis is a
      comparatively inexpensive diagnostic approach to detect this marker in the urine
      sample.

PMID- 22455262
TI  - Outcome of the rubber band ligation with Milligan Morgan haemorrhoidectomy.
AB  - BACKGROUND: Haemorrhoids is a common anorectal disease seen in our society.
      Conservative management is usually adopted for 1st and 2nd degree haemorrhoids.
      Patients who do not respond to above management are the candidates for other
      modalities of treatment which includes sclerotherapy, rubber band ligation,
      cryosurgery and stapler gun or open haemorrhoidectomy. The purpose of study was
      to compare the outcome of the Rubber band ligation with Milligan Morgan
      haemorrhoidectomy in patients with 2nd and 3rd degree haemorrhoids. METHODS:
      Hundred diagnosed admitted patients of uncomplicated 2nd and 3rd degree piles
      were treated either with rubber band ligation (RBL) or open method of Milligan
      Morgan (OH) for the period from January 2007 to December 2007 were included in
      the study. Both procedures were evaluated regarding effectiveness, safety,
      complications after procedures, hospital stay and return to work on a written
      Performa. Patients with 1st and 4th degree haemorrhoids, below the age of 12
      years, bleeding diathesis, associated local anorectal conditions requiring
      surgery, complicated haemorrhoids, recurrent and secondary haemorrhoids were
      excluded from the study. Follow up of all these patients was done in OPD to
      assess any complication and recurrence. Data was analysed through SPSS-16.0.
      RESULTS: One hundred indoor patients with 2nd and 3rd degree haemorrhoids were
      treated either with rubber band ligation or open technique. Most (> 90%) of the
      patients were males. Majority of the patients were in 30-33 years age group.
      Fresh bleeding (90%) and constipation (45%) were the commonest symptoms followed
      by prolapsed, discharge and irritation. Second degree was more common than 3rd
      degree haemorrhoids. Intensive pain was the commonest complain after both the
      procedures, however faecal incontinence was not reported in either group.
      Hospital stay was longer in open technique (70%) compare to few hours to one day
      in rubber band ligation group. Return to work was earlier in patients treated
      with rubber band ligation. CONCLUSION: Rubber band ligation is safe and effective
      method compare to open technique in 2nd and 3rd degree symptomatic haemorrhoids.

PMID- 22455263
TI  - Prevalence and management of anencephaly at Saidu Teaching Hospital, Swat.
AB  - BACKGROUND: Anencephaly is a fatal congenital abnormality characterised by
      absence of cerebral hemisphere and cranial vault. Overall incidence of
      anencephaly is 3.8-6.0/1,000 births. This study was conducted to determine the
      prevalence, diagnosis and management of anencephaly in District Swat. METHODS:
      This prospective study was carried out over a period of one year from January
      2007 to December 2007 at Saidu Teaching Hospital/Saidu Medical College Swat.
      Pregnant women having foetuses with neural tube defects (NTDs) admitted in Labour
      Room/Obstetric Ward of the Saidu Teaching Hospital Swat were selected as
      subjects. Those women who delivered normal babies were taken as control subjects.
      A proper history was taken from each subject and all the relevant information
      were recorded on a proforma. RESULTS: A total of 5,560 subjects were included in
      this study. Out of them, 69 were having NTDs, 63 had anencephaly, 4 had spina
      bifida, and 2 foetuses were having multiple neural tube defects. Prevalence of
      anencephaly was 11.33/1000 births and that of spina bifida was 0.72/1000 births.
      Eighty percent (80%) anencephaly and 50% spina bifida were diagnosed by
      ultrasonography. Most of the cases (52, 75.36%) were delivered through normal
      vaginal delivery after induction. Twelve (17.40%) had spontaneous vaginal
      delivery, 4 (5.80%) had caesarean section, and hysterectomy was done in 1
      (1.45%). CONCLUSION: Anencephaly is common congenital anomaly in Swat.
      Complications can be prevented by implementing screening program for early
      diagnosis, treatment, and management. Prevalence can be decreased by folic acid
      supplementation periconceptionally.

PMID- 22455264
TI  - Maternal factors associated with intrauterine growth restriction.
AB  - BACKGROUND: Intrauterine growth restriction is a major neonatal health issue.
      Maternal factors have been found to have greater impact on IUGR. Studying these
      factors can help in reducing the mortality and morbidity associated with IUGR.
      METHODS: This case-control study was conducted at the department of Paediatrics
      Post-graduate medical institute Lady Reading Hospital Peshawar from March 2008
      April 2009. Small-for-gestational age (SGA, i.e., IUGR cases and n = 200) live
      born babies were compared with appropriate-for-gestational age (AGA, i.e.,
      controls and n = 200) babies. Information regarding socio-demographics of
      mothers, gestational age and birth weight of baby, maternal clinical
      characteristics, and medical and obstetric complications during pregnancy was
      recorded on a pre-designed proforma. Data analysis was done through SPSS-16. To
      find the maternal factors associated with the intrauterine growth restriction,
      multivariable logistic regression was used. We also did two different sets of
      logistic regression analysis for Symmetric and Asymmetric SGA babies as Cases.
      RESULTS: After adjusting for other variables in the multivariable model we found
      that the mothers of IUGR babies were of younger age (OR = 0.8, CI = 0.7-0.9),
      were poor (OR = 2.5, CI = 1.4-4.4) and underweight (OR = 3.5, CI = 1.1-5.7) and
      had anaemia (OR = 2.7, CI = 1.3-5.4) in the index pregnancy, and had history of
      Previous IUGR birth (OR = 9.7, CI = 3.3-18.3) and placenta previa (OR = 3.2, CI =
      1.1-6.6). There was an interaction between pregnancy induced hypertension and
      parity of mother with a primary-para mother with pregnancy induced hypertension
      (PIH) having an increased risk for IUGR babies (OR = 10.1, CI = 1.0-23.2).
      CONCLUSION: The studied factors need special attention in hospital based settings
      in order to improve the perinatal outcome in IUGR babies.

PMID- 22455265
TI  - Acupuncture treatment of facial palsy.
AB  - BACKGROUND: Bell's palsy is an idiopathic, acute peripheral-nerve palsy involving
      the facial nerve which supplies all the muscles of facial expression. This study
      was conducted to evaluate the effects of electro-A=acupuncture on patients with
      facial palsy. METHODS: This study was conducted on patients with facial palsy at
      a private clinic at Peshawar during 1999-2009, and 49 cases were included in the
      study. All those cases that were within first two weeks of illness or who had
      related history of stroke or they had upper motor neuron lesion were not included
      in the study. Electroacupuncture was used as the main therapeutic technique to
      treat these cases. Patients were subjected to acupuncture treatment at four major
      points on the face for 20-25 minutes everyday for 10 days. Specific points were
      used for nasolabial fold and watering of the eye. After rest for a week patients
      were again evaluated and another course of treatment comprising of 5-10 days was
      sufficient in most cases. Frequency of electro-acupuncture is kept at 60-80
      cycles per minute. RESULTS: Total number of patients studied was 49 with duration
      of illness as early as 3 weeks to a year and above. Cases with duration of
      illness from 3 weeks onward showed rapid recovery of palsy symptoms with electro
      acupuncture. All cases showed recovery. Palsy of the angle of the mouth did not
      recover completely. CONCLUSION: Electro-acupuncture is effective in treating
      facial palsy cases.

PMID- 22455266
TI  - Does BMI affect cholesterol, sugar, and blood pressure in general population?
AB  - BACKGROUND: Higher BMI in child hood is also associated with an increase risk for
      coronary heart disease in adulthood. Impaired glucose tolerance is highly
      prevalent in children and adolescents with severe obesity. Positive correlations
      between BMI and glucose, lipids and BP have previously been reported. The
      objective of this study was to find the correlation of BMI with cholesterol and
      sugar level in general population. METHODS: This study was a part of 'Peshawar
      Heart Study', performed at Cardiology Department, Lady Reading Hospital, Peshawar
      in 2008-2009. Individuals with different ages, gender, professions, socioeconomic
      class were randomly selected from general population. Random blood sugar and
      cholesterol was measured with strip method. Height and weight of each individual
      was recorded and BMI calculated. All individuals were asked about any current
      medical illness and whether they were performing any exercise or not. Using SPSS
      13, descriptive statistics were used for frequencies. Bivariate correlations were
      used for measuring correlation between BMI, sugar and cholesterol. Partial
      correlations were used to factor out the effect of other variables. RESULTS: A
      total of 2,270 individuals, 1,798 (79.2%) male and 472 (20.8%) female were
      examined. Mean age was 38.47 +/- 12.66. Mean BMI was 26.38 +/- 4.97. Mean RBS was
      113.7 +/- 47.145. Mean cholesterol was 168.47 +/- 28.23. Exercise was performed
      by 929 (40.90%) individuals. Diabetes was present in 113 (5.0%) and history of
      high cholesterol in 25 (1.1%) persons. When bivariate correlation analysis were
      done systolic BP, diastolic BP, RBS and cholesterol had positive correlation with
      BMI [correlation coefficient of 0.317 (p < 0.000), 0.319 (p < 0.000), 0.125 (p <
      0.000) and 0.205 (p < 0.000) respectively]. These variables also showed a
      positive correlation among themselves. After factoring out the effects of age,
      exercise, gender and current medical status on the above correlations, the
      correlation of RBS and cholesterol with BMI decreased to 0.025 (p = 0.232) and
      0.135 (p < 0.000) respectively and between sugar and cholesterol decreased to
      0.018 (p = 0.401). CONCLUSION: In general population BMI is positively correlated
      with RBS and cholesterol. With the effect of age, sex, exercise and current
      medical status, this correlation is reduced.

PMID- 22455267
TI  - Short duration head-up tilt test: a comparison with conventional long protocol in
      patients of orthostatic intolerance.
AB  - BACKGROUND: Orthostatic intolerance is development of symptoms during upright
      standing relieved by recumbency. An individual's predisposition to orthostatic
      intolerance (development of symptoms during upright posture) can be identified by
      Head-up Tilt Test (HUT). The aim of the present study was to compare the
      diagnostic yield (Percentage of patients tested positive) of short duration with
      conventional HUT. METHODS: The study was conducted in Islamic International
      Medical College, Rawalpindi in collaboration with Armed Forces Institute of
      Cardiology/National Institute of Heart Diseases. A total number of 100 patients
      with orthostatic intolerance were studied. The conventional and short duration
      HUT protocols were compared. Conventional protocol had a passive tilt phase of 30
      minutes and drug provocation phase of 20 minutes while the short duration
      protocol had both phases of 15 minutes, thereby reducing the test duration by 20
      minutes. All patients underwent short duration HUT and patients with positive
      test were considered positive for conventional HUT as well. Patients having
      negative short duration HUT underwent conventional HUT after one week. Comparison
      was done using Chi-square statistics and p < 0.05 was considered significant.
      RESULTS: Diagnostic yield of short duration and conventional HUT was 53% and 63%
      respectively with no statistically significant difference between the two
      protocols (p = 0.15). CONCLUSIONS: Head-up tilt test (HUT) is an effective
      investigative tool for orthostatic intolerance with satisfactory diagnostic
      yield. Short duration HUT may be substituted for conventional HUT to save time
      and to accommodate more patients.

PMID- 22455268
TI  - An audit of length of bone marrow trephine biopsies at a tertiary care hospital.
AB  - BACKGROUND: Bone marrow trephine biopsy is a well established minor surgical
      procedure for the inspection of bone marrow usually done along with bone marrow
      aspiration. The objective of this study was to evaluate the length of trephine
      biopsies and the rate of positivity for diagnosis as well as unfit biopsies in
      various length ranges. METHODS: This retrospective study was conducted at Fauji
      Foundation Hospital and Foundation University Medical College Rawalpindi from Jan
      2007 to Dec 2009. A total of 394 trephine biopsy reports were collected and
      reviewed. The criterion for adequate trephine biopsy was > or = 1.5 Cm. The
      biopsies were divided into four groups according to length, i.e., group-1: > or =
      1.5 Cm, group-2: 1-1.4 Cm, group-3: 0.5-0.9 Cm, and group-4: < 0.5 Cm. The
      adequacy of trephine biopsy length and rate of positive diagnosis as well as
      unfit biopsies were compared. RESULTS: Total 394 trephine biopsies were reviewed.
      Group-1 included 88 biopsies and 87 (98.9%) had positive diagnosis. Group-2
      included 137 biopsies and 133 (97.1%) had positive diagnosis. Group-3 included 99
      biopsies and 91 (92%) had positive diagnosis. Group-4 included 70 biopsies and 57
      (81.4%) had positive diagnosis. There was no significant difference between group
      1 and group-2 for the rate of positivity of diagnosis (p = 0.65). In group-1, 1
      (1.1%) was unfit for evaluation, in group-2, 4 (2.9%) were unfit, in group-3, 8
      (8%) were unfit, and in group-4, 13 (18.5%) were unfit for evaluation. Total 26
      trephine biopsies were unfit for evaluation, out of which 13 (50%) belonged to
      group-4. Trephine biopsies that were unfit for evaluation were 4 (4.9%) in 2007,
      17 (10.5%) in 2008, and 5 (3.3%) in 2009. CONCLUSION: Although 22.3% biopsies
      were of recommended length there was no significant difference in rate of
      positive diagnosis between biopsies of > or = 1.5 Cm and 1-1.4 Cm.

PMID- 22455269
TI  - Beta-thalassaemia trait: haematological parameters.
AB  - BACKGROUND: Beta-Thalassaemia syndromes are a group of hereditary disorders
      characterised by a genetic deficiency in the synthesis of beta-globin chains due
      to a defect in beta-globin genes. The objective of this study was to determine
      the haematological features of beta-thalassaemia trait (BTT). and to determine
      the sensitivity of Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin
      (MCH) and Mentzer Index (ML) as a screening tool for beta-thalassaemia trait.
      METHODS: A descriptive study was conducted in Hayatabad Medical Complex, Peshawar
      from May 2009 to May 2010 with 203 subjects having BTT. Blood samples were
      collected in EDTA anti-coagulated tubes. RBC indices were taken as part of
      complete blood count (CBC) by haematology analyser, and Haemoglobin (Hb)
      electrophoresis was done to determine the HbA2 percentage. The data was collected
      and analysed on statistical software for demographic details, RBC indices and
      HbA2 levels. RESULTS: Out of 203 patients, 92 (45%) were males and 111 (55%) were
      females. Most patients tested were in the 15-45 year age group. One-hundred-sixty
      (79%) patients had anaemia. MCV was lower than 76 fl in all the cases. Mean MCV
      was 59.1 fl. MCH was low, the mean MCH being 19.3 g/dl. MCH < 26 gave sensitivity
      of 99% in detecting BTT. We calculated MI for these cases and found out that it
      was < 12 in 75% of cases and < 15 in 197 (97%). CONCLUSION: Beta-thalassaemia
      traits present with a microcytic hypochromic blood picture, detected on simple
      haematology analysers as low MCV and MCH and MI which provide a useful screening
      tool for beta-thalassaemia trait.

PMID- 22455270
TI  - Misoprostol for the purpose of mid-trimester termination of pregnancy: a
      comparative study with prostaglandin F2 alpha.
AB  - OBJECTIVE: To compare the efficacy of misoprostol verses prostaglandin F2alpha
      (PGF2alpha) in the medical management of termination of mid-trimester pregnancy
      due to medical reasons. METHODS: This experimental study was conducted in
      Obstetrics and Gynaecology Department, Bahawal Victoria Hospital, Bahawalpur for
      a period of 6 months from April 2005 to September 2005. Time interval between
      induction with misoprostol or PGF2alpha and expulsion of foetus, number of
      tablets of misoprostol used and total dose of injection PGF2alpha used for
      termination of pregnancy as well as the complications experienced with both
      drugs. Fifty patients of 18-35 years of age were randomly selected who presented
      to Gynaecology and Obstetrics outdoor with mid-trimester foetal loss or
      congenitally malformed foetus incompatible to life, confirmed on ultrasonography.
      These women were randomised to receive either intravaginal misoprostol or extra
      amniotic PGF2alpha. RESULTS: Ninety-six percent of cases were managed
      successfully with Misoprostol as compared to 92% where PGF2alpha was tried (p >
      0.5). Mean induction to expulsion duration for misoprostol and PGF2alpha were
      9.02 +/- 4.57 and 16.04 +/- 6.22 hours respectively (p < 0.5). Complications
      profile was low especially in cases of PGF2alpha and only one case experienced
      significant haemorrhage. CONCLUSION: Misoprostol and PGF2alpha were found to be
      of same success rate but former was found to be more efficacious in terms of
      induction to expulsion duration.

PMID- 22455271
TI  - Single versus 3-dose antibiotic prophylaxis in clean and clean contaminated
      operations.
AB  - BACKGROUND: Infection is a great problem in surgery and is encountered by all
      surgeons by nature of their craft; they invariably impair the first line of host
      defence. Bacteria may enter the wound during or after the operation and may be of
      endogenous or exogenous origin. The objective of this study was to determine the
      effectiveness of preoperative antibiotic prophylaxis in reduction of
      postoperative wound infection in clean and clean contaminated procedures and to
      compare the cost of antibiotic prophylaxis in both groups. METHOD: This was a
      prospective study done on patients in General Surgery Department, Al-Noor
      Specialist Hospital, Holly Makkah, Saudi Arabia from 1st April 2006 to 30th March
      2007. Total 400 patients were divided into 2 groups of 200 patients each: Group-A
      received single dose antibiotic prophylaxis, and Group-B received 3 doses of
      antibiotic therapy. Only clean and clean contaminated procedures were included
      and results were compared. RESULTS: In Group A, clean procedures (Group-Al) were
      110, and clean contaminated (Group-A2) were 90 patients. In clean procedure, rate
      of infection was 5 out of 110 (4.54%) and in clean contaminated procedures it was
      3 out of 90 (3.33%). In Group B, in clean procedures (Group-B1), rate of
      infection was 7 out of 90 (7.77%), while in clean contaminated procedures (Group
      B2) it was 9 out of 110 (8.18%) patients. Over all wound infection rate after
      single dose antibiotic prophylaxis was 4% in both procedures and 8% after 3-dose
      antibiotic therapy. CONCLUSION: Single dose antibiotic prophylaxis is as
      effective as 3-dose therapy in clean and clean contaminated procedures to prevent
      wound infection and is cost-effective.

PMID- 22455272
TI  - Root resorption of permanent incisors during three months of active orthodontic
      treatment.
AB  - BACKGROUND: Root resorption is one of the most common and undesirable sequelea of
      orthodontic treatment. The aim of this study was to evaluate the amount of root
      resorption in permanent incisors during 3 month active period of fixed
      orthodontic appliance therapy using periapical radiographs. METHODS: Periapical
      radiographs of a total of 138 permanent teeth (n = 138, mandibular n1 = 52,
      maxillary n2 = 86) were evaluated for root resorption. All patients were treated
      with 3M MBT multi-bonded, pre-adjusted appliances with 0.022 inch slots. Initial
      levelling and alignment was achieved with 0.0175 inch co-axial wires. All four
      incisors (maxillary and mandibular) were measured for any change in root length.
      The change in root length between T0 (pre-treatment) and T1 (post-treatment) was
      measured in millimetres and expressed in terms of percentage of original root
      length. RESULTS: The mean pre treatment (T0) root length for the maxillary teeth
      (n1 = 62) was 19.27 +/- 2.86 mm and 20.01 +/- 2.57 mm for the mandibular teeth
      (n2 = 31). The post-treatment (T1) root length for the maxillary teeth was 18.96
      +/- 2.85 mm and 19.49 +/- 2.4 mm for the mandibular teeth showing a mean
      resorption of 0.31 mm and 0.52 mm for the maxillary and mandibular teeth
      respectively. CONCLUSION: Root resorption was strongly correlated with active
      orthodontic appliance therapy with maxillary and mandibular incisors being most
      susceptible. It was found that root resorption can be detected even in the early
      levelling and alignment stages of orthodontic treatment.

PMID- 22455273
TI  - Healthcare waste management (HCWM) in Pakistan: current situation and training
      options.
AB  - BACKGROUND: Hospitals in Pakistan produce about 250,000 tons of waste per year.
      Hospital waste has been reported to be poorly handled and managed by the hospital
      staff and administration respectively. This leads to environmental and health
      consequences within hospitals as well as to outside population. Our study aimed
      to describe the qualitative results of observations of ten large private and
      public hospitals in the cities of Rawalpindi and Islamabad Pakistan. METHODS: The
      qualitative data was obtained through direct and indirect observations on
      hospital staff including doctors, nurses, sweepers and persons in administration
      and the way they handled the waste. Also direct observations of the hospitals
      premises inside and outside were made and noted. We also describe the process of
      involving the hospital staff for trainings. RESULTS: Our results showed that
      almost all of the hospitals did not have practice of HCWM on their priority.
      Segregation, handling, storage, transportation and disposal of waste were below
      WHO and Pakistan bio-safety rules 2005 standards. The ten hospitals did not have
      HCWM rules and regulations in place hence the staff do not follow the best
      practices in this regard which causes numerous health and environmental
      consequences not only within the catchment area but also to patients and staff.
      CONCLUSIONS: Our study highlights the lack of HCWM practices within the ten
      public and private hospitals in two major cities in Pakistan. There is need of
      trainings of hospital staff in Pakistan. We also found that such trainings are
      highly feasible if accompanied with incentives to participants.

PMID- 22455274
TI  - Optical urethrotomy in strictures following fracture pelvis.
AB  - BACKGROUND: Management of posterior urethral injuries with pelvic fracture
      remains a major controversy and has always been a challenge to urologists.
      Objective of this study was to see the outcome of optical internal urethrotomy in
      treatment of urethral strictures following fracture pelvis. METHODS: This
      prospective study was conducted at the Urology Department, Lady Reading Hospital,
      Peshawar from January 2007 to July 2008. A total of 45 male patients (20-60 years
      of age) and having urethral strictures following fracture pelvis were treated
      with internal optical urethrotomy. Follow-up ranged from 3 months to 1 year.
      RESULTS: Fracture pelvis resulting from the road traffic accident, was the cause
      of urethral stricture. The good and fair results of internal optical urethrotomy
      were 68.56% patients who were treated with single internal optical urethrotomy.
      Internal optical urethrotomy was repeated in 22.86% of patients. Clean
      intermittent self urethral dilatation was applied as adjuvant treatment to
      prevent recurrence of stricture for variable period ranging from 1 to 3 months.
      CONCLUSION: Internal optical urethrotomy is safe and effective procedure for
      short yet inaccessible strictures from the perineum.

PMID- 22455275
TI  - Early results of oesophagectomy for carcinoma oesophagus in 1008 cases.
AB  - OBJECTIVE: To determine the early results of 1008 oesophagectomies done for
      carcinoma oesophagus over a 9 years period. METHODS: This observational
      descriptive study was conducted at Department of Cardiothoracic Surgery, Lady
      Reading Hospital, and Khyber Medical Centre Peshawar from June 2002 to June 2011.
      All patients had apart from routine investigations, Barium studies, Endoscopy and
      biopsy, CT thorax/upper abdomen with oral and I/V contrast and abdominal
      ultrasound. The operative approaches included left thoracolaparotomy with left
      neck anastomosis, transhiatal, left thoracolaparotomy with Roux en-Y, McKeown
      with right decortication, Ivor Lewis and left thoracolaparotomy with left
      decortication. All operations were done by one surgical team. The hospital
      records and operation reports of these patients were carefully analysed for
      demographic feature; operative approach and outcome. RESULTS: Out of 1008 cases,
      698 were males and 310 were females with a mean age of 51.6 years. The age range
      was 17-80 years. Out of 1008 cases 611 (60.61%) cases had lower one third
      tumours, 384 (38.09%) cases had middle one third tumours while 13 (1.28%) tumours
      were just below the thoracic inlet. Of the 611 lower 1/3 tumours stomach
      involvement was present in 271 (44.35%) cases. Adenocarcinoma was present in 516
      (51.19%) cases, squamous cell carcinoma was present in 485 (48.11%),
      adenosquamous was 6 (0.59%) and carcinoma in situ was present in 1 case (0.09%).
      Morbidity was 63/1008 (6.25%), and comprised anastomotic leaks 15, aspiration
      pneumonia 13, wound infection 13, hoarseness 8, and strictures 14, 30-day
      mortality was 23/1008 (2.28%) and causes included aspiration pneumonia
      respiratory failure (5), myocardial infarction (4), anastomotic leak (6),
      tracheal injury (2), and presumed pulmonary embolism (6). CONCLUSION: More than
      1000 cases in 9 years is a very high oesophageal workload for malignancy.
      Morbidity of 6.25% and mortality of 2.28% shows that such major operations can be
      done safely in thoracic centres.

PMID- 22455276
TI  - Pattern of coronary artery disease with no risk factors under age 35 years.
AB  - BACKGROUND: Coronary artery disease (CAD) is no more deemed to be an ailment of
      the 4th or 5th decade; rather an earlier age incidence is not infrequently
      encountered in our population. However, there are a few data regarding CAD in
      young adults, and much about its underlying pathology still remains undetermined.
      The objective of this study was to delineate the coronary arterial disease
      pattern in adults under the age of 35 years, but having no known coronary risk
      factors. METHODS: This prospective study was conducted at the Cardiology
      Departments of all 3 public sector tertiary care hospitals in Peshawar from Jun
      2008 to Dec 2009. After having excluded the traditional risk factors for CAD,
      patients under the age of 35 years with objective evidence of CAD were subjected
      to percutaneous coronary angiography. RESULTS: Out of a total of 104 patients, 85
      (81.73%) patients were men, and 19 (18.27%) were women. The mean age of the whole
      group was 32.66 +/- 3.237 (22-35) years. Significant CAD (> 50% diameter
      narrowing of at least one major coronary artery) was found in 87 (83.7%) patients
      while 17 (16.3%) patients had non-atherosclerotic coronary artery disease,
      including 12 (11.53%) patients having normal coronary arteries, 1 (1%) patient
      had anomalous origin of right coronary artery (RCA), 1 (1%) patient had coronary
      arteritis, 2 (1.92%) patients had coronary artery ectasia, and 1 (1%) patient had
      a myocardial bridge over left anterior descending artery (LAD). Among the
      patients with significant CAD, the prevalence rate of one, two and three vessel
      disease was 54 (51.9%), 22 (21.2%) and 11 (10.6%) respectively. Almost 50% of the
      lesions occurred in LAD followed by 25% in RCA and 20% in circumflex, while only
      one patient (1%) had isolated significant CAD of left main coronary artery.
      Osteal segments were involved in 10%, proximal in 61%, mid in 21% and distal
      segments in 7% of the lesions. CONCLUSION: In the younger age group, CAD is
      mostly a disease of men, single vessel CAD predominates with LAD involvement
      mostly, predominant osteal to proximal segment involvement of vessels, and a much
      higher incidence of normal coronaries and non-obstructive CAD is met with.

PMID- 22455277
TI  - Clinical characteristics of patients with dengue fever: report of 48 patients in
      2010.
AB  - BACKGROUND: Dengue fever is a mosquito born viral disease. It occurs in tropical
      and sub-tropical areas of the world. Symptoms appear 3-14 days after the
      infective bite. Mortality can occur in dengue hemorrhagic fever and dengue shock
      syndrome unless prompt and adequate management is provided. OBJECTIVE: To
      determine the clinical and epidemiological characteristics along with outcome of
      patients with dengue fever (DF) dengue hemorrhagic fever (DHF) and dengue shock
      syndrome (DSS). DESIGN: Prospective, follow-up study. PLACE AND DURATION OF
      STUDY: Department of Medicine, Shaikh Zayed Federal Postgraduate Medical
      Institute, Lahore from 3rd Oct 2010 to 20th Nov 2010. PATIENTS AND METHODS:
      Specific serological tests for dengue fever were done in all 60 patients admitted
      with suspected diagnosis of DF, DHF and DSS. Forty-eight confirmed cases were
      evaluated for age, gender, clinical features and outcome of the disease. RESULTS:
      Forty-eight out of 60 patients had positive serology for dengue fever. Male to
      female ratio was 1.09:1. Their ages ranged from 5 years to 68 years with the mean
      of 31.5 +/- 15.2 years. DF, DHF and DSS were found in 71%, 19% and 10% cases
      respectively. Common presentations were fever (100%), skin rash (83.33%), myalgia
      (69.75%), restlessness (66.67%) and rigors and chills (66.67%). All, except one
      patient improved clinically. One patient died on second day of admission.
      CONCLUSION: Dengue fever, a viral infection is re-emerging as a serious public
      health problem. Fever, rash, myalgia with rigors and chills were common
      presenting features.

PMID- 22455278
TI  - Levosulpiride in premature ejaculation.
AB  - BACKGROUND: Premature ejaculation is one of the most common sexual disorders. A
      large number of treatment options have been used so far for the treatment of this
      dysfunction and still a large number of experts are doing research in this field.
      Here we have tried to research on the beneficial effects of levosulpiride in the
      treatment of PE. METHODS: Eighty-eight patients form different areas of Hazara
      division suffering from PE were chosen. Sixty-four patients were given
      levosulpiride and the remaining 24 patients were given placebo. RESULTS: Out of
      64 patients who have been given levosulpiride, 30 patients showed very good
      improvement, 14 patients showed some improvement, 14 patients showed little and 6
      patients showed no improvement. CONCLUSION: Levosulpiride have very good
      beneficial effects in the treatment of PE.

PMID- 22455279
TI  - Comparative therapeutic response to pegylated interferon plus ribavirin versus
      interferon alpha-2b in chronic hepatitis C patients.
AB  - BACKGROUND: Hepatitis C is an epidemic worldwide since discovery in 1989.
      Conventional interferon alpha-2b plus Ribavirin therapy was started in 1998 but
      over all sustained viral response (SVR) rates are much below the desired rates to
      eradicate the diseases and stopping its epidemic. This study was conducted to
      access the therapeutic and cost-effectiveness of long acting pegylated interferon
      alpha-2b plus Ribavirin therapy verses conventional interferon alpha-2b plus
      Ribavirin. METHODS: This comparative study was done at PAF Hospital Shorkot Cantt
      from July 2005 to July 2008. One hundred anti-HCV positive patients were selected
      randomly for the study according to willingness due to cost affordability of the
      patients for conventional interferon. Group-A was labelled as pegylated
      interferon alpha-2b plus Ribavirin group, and Group-B interferon alpha-2b plus
      Ribavirin group. Both groups were given treatment for 24 weeks. Early virological
      response (EVR) was accessed at 12 weeks of treatment. Sustained virological
      response (SVR) in both the groups was done at 24th week during the treatment and
      6 monthly after treatment for 2 years. Initially non-responders and relapsed
      patients within 2 years of treatment were re-treated for 24 weeks with the same
      treatment. In both groups nonresponders and relapsed patients were labelled as
      resistant patients. Both groups were followed with same protocol for 2 years.
      RESULTS: Out of 100 patients included in the study, 34% were females and 66% were
      males. Group-A patients over all showed 94% SVR as compare to 80% in Group-B in 2
      year follow-up. Group-A showed 6% resistant patients as compare to Group-B (20%).
      Conventional interferons were better tolerated. Higher incidence of side-effects
      was seen in Group-A. CONCLUSION: Pegylated interferon plus Ribavirin showed 94%
      SVR in 2 years. Pegylated interferon plus Ribavirin is the treatment of choice.

PMID- 22455280
TI  - Orofacial reconstruction with local flaps at AFID.
AB  - BACKGROUND: Reconstruction of oral cavity is often a difficult challenge as it
      involves the restoration of both the cosmetics and preoperative function.
      Understanding the oral cavity anatomy as well the functional capacities of its
      various subunits is required to achieve good results. The stage of the disease
      and extent of resection are the most significant parameters that must be kept in
      mind before planning for reconstruction. Aim was to evaluate the success rate of
      various local flaps in oral reconstruction as well as to conclude whether or not
      the reconstruction method influences postoperative quality of life. METHODS: This
      is a descriptive study carried out at Armed Forces Institute of Dentistry, (AFID)
      Rawalpindi. Sample size comprises of 24 subjects, 16 males and 8 females, who
      reported to the diagnostic department of AFID from 15 March 2007 to 15 March
      2010. RESULTS: A total of 24 patients with oral squamous cell carcinoma were
      treated in 3 years, out of them 16 (66.7%) were male and 8 (33.3%) were female.
      The peak incidence was in the 6th and 7th decade of life (37.5%). The most common
      site involved was the alveolus 37.5% in the reported cases followed by tongue
      (25%) and buccal mucosa (25%). In 8 (33.3%) patients local resection was
      performed, in 4 (16.7%) patients resection along with neck dissection was done.
      In 12 (50%) patient tumour resection followed by neck dissection and immediate
      reconstruction was also done out of these 12 patients nasolabial flap
      reconstruction was done in 6 patient (25%), Karapandzic in 4 (16%) patients, and
      fan flap in 2 (8%) patients. No complication noticed other than wound dehiscence
      (2 patients), microstomia and circumoral scarring (1 patient). Mean hospital stay
      was 7 days.

PMID- 22455281
TI  - Presentation of congestive cardiac failure in children with ventricular septal
      defect.
AB  - BACKGROUND: While there is much data on cardiac problems of adults, there is a
      limited statistical data available to evaluate the magnitude of the cardiac
      problems in children in Pakistan. Many of these children present with recurrent
      chest infections and congestive cardiac failure (CCF), and are managed by general
      practitioners. A careful search for underlying cardiac problems and awareness
      about the presentation of CCF and its magnitude will definitely decrease the
      morbidity and mortality of these children. The objective of this study was to see
      the frequency and clinical presentation of CCF in children with Ventricular
      Septal Defect (VSD). METHODS: Forty-nine patients met the preset criteria during
      the study period of 6 months. A detailed history and physical examination with
      special emphasis on symptoms and signs was sought and the findings were noted in
      a questionnaire. Data was analysed using SPSS-11. Frequencies and percentages
      were calculated for all categorical variables. RESULTS: CCF in VSD was found more
      in males, with a male to female ratio of 1.45:1. Majority (63.1%) of the patients
      presented in infancy. The common symptoms at presentation were dyspnoea (98%),
      cough (83.7%), and feeding difficulty (9.6%). Other important symptoms were
      fever, fatigue, failure to thrive, sweating and wheezing. The common physical
      signs in order of frequency were murmur 98%, tachypnoea 91.8%, tachycardia 89.8%,
      hepatomegally 89.9% and crackles in chest 85.7%. Other presenting signs were
      displaced apex beat 57%, oedema 28.6% and chest deformity 20.4%. Regarding the
      type of VSD, perimembranous was the commonest 61.2% as confirmed by
      echocardiography. CONCLUSION: This study was done on a smaller scale in
      hospitalised children. The exact studies regarding CCF in paediatric patients are
      scarce. There is a need to design more studies in children with CCF. Early
      recognition of signs and symptoms of CCF on paediatric patients with VSD and
      awareness at primary health care level can prevent the delay in the diagnosis and
      early referrals by GPs to hospital setup will definitely reduce the morbidity and
      mortality.

PMID- 22455282
TI  - Frequency of hepatitis B in asymptomatic patients of District Headquarter
      Hospital Kotli, Azad Kashmir.
AB  - BACKGROUND: Hepatitis B is prevalent throughout the world including Pakistan. A
      large proportion of patients suffering from Hepatitis B may be asymptomatic and
      can transmit the disease to healthy population. Objectives of this study were to
      estimate the frequency of Hepatitis B in asymptomatic adult population coming to
      District Headquarter Hospital Kotli, Azad Kashmir and to determine the risk
      factors associated with its transmission. METHODS: This was a cross-sectional
      study extending from January to December 2008. Subjects were randomly selected
      from those who attended the medial OPD of DHQ Hospital Kotli, Azad Kashmir for
      non-Hepatitis related problems. Both males and females between the ages of 15-80
      years were included in the study. Blood samples taken from selected subjects were
      analysed for Hepatitis B surface antigen (HBsAg) by Immunochromatographic kit
      methods (ICT). Hepatitis B positive samples were further confirmed by third
      generation ELIZA. The patients thus confirmed were interrogated for different
      risk factors associated with transmission of Hepatitis B. RESULTS: A total of
      9,564 patients were analysed. Out of them 4230 (44.22%) were males and 5334
      (55.77%) were females. Overall 141 (1.47%) patients were positive for HBSAg, 71
      (1.68%) males and 70 (1.31%) females. Patients between 21-30 years of age were
      most commonly effected (35.46%, n = 50). Blood transfusion was the most common
      risk factor (24.82%, n = 35) associated with Hepatitis B transmission followed by
      dental procedures (14.18%, n = 20). CONCLUSION: Frequency of Hepatitis B in
      asymptomatic people in this study was quite high. Blood transfusions and dental
      procedures were the most common risk factors associated with the transmission of
      Hepatitis B.

PMID- 22455284
TI  - Relationship of life style choices on body fat mass in young adults.
AB  - BACKGROUND: Healthy diets and regular, adequate physical activity are major
      factors in the promotion and maintenance of good health throughout entire life
      course. Accumulation of fat occurs whenever energy consumed by food and drinks
      exceeds that which can be utilised by an individual's metabolism and physical
      activity. The objective of this study was to estimate the effect of lifestyle
      characteristics of a representative segment of medical students in terms of fast
      food preferences and participation in physical activity with respect to Body Mass
      Index (BMI). METHODS: This cross-sectional study was carried out in Physiology
      Department, Bahria University Medical & Dental College, Karachi on 192 students
      of 1st and 2nd year MBBS. Body Mass index of students was calculated. They were
      classified into 4 groups with BMI < or = 18.5, 18.6-23, 23.1-25 and > or = 25
      respectively. A life style questionnaire, based on preferences for
      healthy/unhealthy food, dietary habits and participation in physical activity was
      filled. RESULTS: Most of medical students (65%) had BMI less than 23. It was
      because of selection of healthy dietary pattern with nutritious food (p < 0.09)
      and participation in outdoor games (p < 0.03). Males who had high BMI showed a
      tendency to daily intake of fast food (p < 0.03). Walking in both the sexes had a
      positive impact in maintaining normal BMI (p = Males < 0.04, females < 0.001).
      CONCLUSION: Obesity can be prevented by innovative approaches, easiest of which
      is to promote active life styles with intake of healthy diet and involvement in
      physical activity.

PMID- 22455283
TI  - Screening of hepatitis B and C among people visiting general practice clinics in
      a rural district of Sindh, Pakistan.
AB  - BACKGROUND: Hepatitis B (HB), Hepatitis C (HC) and their risk factors are amongst
      the major health problems in developing countries including Pakistan. This study
      aimed to screen for HB and HC among people who visited General Practice clinics
      and also to identify the differences of screening positive cases by age and sex.
      METHODS: This was a retrospective study conducted in Tando Muhammad Khan city,
      one of the rural districts of Sindh. All together we reviewed 5989 laboratory
      reports of people for hepatitis B and C on consecutive basis from two
      laboratories. A pre-designed and structured perform was used to collect the
      required information. Chi-squared test and univariate analysis was calculated to
      assess the difference in HB and HC proportion by age groups and sex. RESULTS: One
      fourth of reports were positive for at least one entity whereas 8% and 17% of
      reviewed reports of adults (> 18 years and above) were screened positive for HB
      and HC respectively. Positive screened tests were higher among older age group
      compared to young age group (HB: older age group = 56.6% vs. younger age group =
      43.4%; OR = 1.07) and (HC: older age group = 58.3% vs. younger age group = 41.7%;
      OR = 1.08). In the same way, positive screened tests were higher among men
      compared to women (HB: men = 67.0% vs. women = 33.0%; OR = 1.2) and (HC: men =
      62.0% vs. women = 38.0%; OR = 1.3), CONCLUSION: A large proportion of people were
      screened positive for HB and HC inthis study. Prevention and screening are
      suggested at larger scale for urgent planning and implementation of intervention
      strategies in this regard. Further research is also recommended to explore this
      important health issue at large scale.

PMID- 22455285
TI  - Relationship of joint hypermobility and musculoskeletal problems and frequency of
      benign joint hypermobility syndrome in children.
AB  - BACKGROUND: The majority of individuals with joint hypermobility remain
      asymptomatic. However, those associated with Benign Joint Hypermobility Syndrome
      (BJHS), develop a number of systemic manifestations. Our objective was to
      determine the relationship between joint hypermobility and musculoskeletal
      problems, and frequency of BJHS in children and adolescents. METHOD: This cross
      sectional observational descriptive study was conducted at Outpatient Department,
      The Children's Hospital, Lahore, Pakistan. A total of 872 individuals (4-18 year)
      were examined for hypermobile joints using Beighton score > or = 4. A
      questionnaire was implied to get data regarding demographic profile,
      musculoskeletal and extra-articular complaints, family history of joint problems
      and daily activity. Brighton's criteria were implied for diagnosis of BJHS.
      RESULTS: The frequency of joint hypermobility was 37.0%; male 39.5%, and female
      34.2% (p = 0.1). There was a gradual decline in mean Beighton score with age. The
      female population showed increase in mean Beighton score around 16-17 year age.
      Arthralgias and back pains 7.7% vs. 1.6%, (p < 0.001), and hernias 2.5% (p =
      0.03) were significantly higher in individuals with joint hypermobility. History
      of joint problems in the family was also significantly higher in children with
      joint hypermobility (p = 0.01). BJHS was detected in 4.8% children (male 3.6% and
      female 6.3%, p = 0.06). Arthralgias (51.0%), hernias (16.3%), joint dislocations
      (8.2%) and varicose veins (8.2%) were the most common presentations. CONCLUSION:
      BJHS is common among children. Arthralgias, back pains and hernias are
      significantly higher in these individuals.

PMID- 22455286
TI  - Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension.
AB  - BACKGROUND: Hypertensive left ventricular hypertrophy (LVH) is associated with
      increased risk of arrhythmias and mortality. Objective was to investigate the
      prevalence of cardiac arrhythmias and LVH in systemic hypertension. METHODS: In
      all subjects blood pressure was measured, electrocardiography and
      echocardiography was done. Holter monitoring and exercise test perform in certain
      cases. There were 500 hypertensive patients, 156 (31.2%) men and 344 (69%) women
      > 30 years of age in the study. Among them 177 (35.4%) were diabetic, 224 (45%)
      were dyslipidemia, 188 (37.6%) were smokers, and 14 (3%) had homocysteinemia.
      Duration of hypertension (HTN) was > or = 2 years). Mean systolic BP (SBP) was
      180 +/- 20 mm Hg and diastolic BP (DBP) was 95 +/- 12 in male and female
      patients. Left ventricular mass index (LVMI) was 119.2 +/- 30 gm/m2 in male while
      103 +/- 22 gm/m2 in female patients. Palpitation was seen in 126 (25%) male and
      299 (59.8%) female patients. Atrial fibrillation was noted in 108 (21.6%) male
      and 125 (25%) female patients, 30 (6%) male and 82 (16.4%) female patients had
      atrial flutter. Ventricular tachycardia was noted in 37 (7.4%) male and 59
      (11.8%) female patients. Holter monitoring showed significant premature
      ventricular contractions (PVC'S) in 109 (21.8%) male and 128 (25.69%) female
      patients while Holter showed atrial arrhythmias (APC'S) in 89 (17.8%) males and
      119 (23.8%) females. Angiography findings diagnosed coronary artery disease in
      119 (23.8%) with CAD male and 225 (45%) without CAD while 47 (9.4%) females
      presented with CAD and 109 (21.8%) without CAD. CONCLUSION: A significant
      association has been demonstrated between hypertension and arrhythmias. Diastolic
      dysfunction of the left ventricle, left atrial size and function, as well as LVH
      have been suggested as the underlying risk factors for supraventricular,
      ventricular arrhythmias and sudden death in hypertensives with LVH.

PMID- 22455287
TI  - Testicular versus epididymal spermatozoa in intracytoplasmic sperm injection
      treatment cycles.
AB  - BACKGROUND: Normal fertilization and ongoing pregnancy can be achieved using
      intracytoplasmic sperm injection (ICSI), even with severely immature spermatozoa.
      However, the published literature documents conflicting results as to the outcome
      of ICSI. METHODS: Surgical extraction of spermatozoa in 111 ICSI treatment cycles
      performed over five years at the Assisted Conception Unit (ACU), University
      College Hospital (UCH), was retrospectively evaluated to compare the outcome of
      ICSI treatment using either testicular or epididymal spermatozoa. RESULTS: A
      higher normal fertilization rate and lower abnormal fertilization rate was
      observed in the epididymal spermatozoa group than in the testicular spermatozoa
      group. Embryo development on day 3 after fertilization and implantation was
      significantly better in the epididymal spermatozoa group. Clinical and ongoing
      pregnancy rates were higher and the spontaneous miscarriage rate lower in the
      epididymal spermatozoa group, but only the clinical pregnancy rate reached
      statistical significance. CONCLUSIONS: The origin of surgically extracted
      spermatozoa has an effect on the success of assisted reproduction using ICSI, and
      the immaturity of testicular spermatozoa may affect fertilization, embryo
      development, implantation and pregnancy.

PMID- 22455288
TI  - Response to standard interferon A2b and ribavirin combination therapy in chronic
      hepatitis C treatment naive patients.
AB  - BACKGROUND: Treatment of Chronic Hepatitis C is now well established with
      conventional interferon or pegylated interferon in combination with ribavirin.
      Peginterferon Alfa and Ribavirin for 6 to 12 months is currently approved initial
      therapy, which is expensive. Response of our patients to standard Interferon
      alpha-2b and ribavirin for 24 weeks have been studied. The objective of this
      study was to asses Sustained Viral Response (SVR) with standard Interferon A2b
      and Ribavirin combination treatment in chronic Hepatitis C patients. METHODS:
      This quasi-experimental study was conducted at Combined Military Hospital, Quetta
      from Jan 2006 to Jun 2007. One hundred and three patients, with 20-60 years of
      age suffering from chronic Hepatitis C were selected on the basis of raised ALT,
      positive anti-HCV antibodies, evidence of viraemia by quantitative PCR for HCV
      RNA and liver biopsy. All patients were started on same brand of Interferon alpha
      2b, 3 MIU subcutaneously, thrice weekly and oral Ribavirin (1,000-1,200 mg/day)
      for 24 weeks. End treatment response (ETR) after completion of treatment and SVR
      six months after ETR were recorded. RESULTS: The 103 patients, 85 males and 18
      females with mean age of 21-48 years completed the treatment for 24 weeks. Mean
      ALT was 96.17 (SD +/- 49.98). End treatment response (ETR) was 89.3% (p = 0.032).
      Sustained Viral Response after 6 months of treatment was 86.4% (p = 0.034).
      CONCLUSION: Standard Interferon and Ribavirin had excellent SVR. It is effective
      as well as economical treatment in Chronic Hepatitis C patients.

PMID- 22455289
TI  - Vaginal carriage rate of group B Streptococcus in pregnant women and its
      transmission to neonates.
AB  - BACKGROUND: Maternal vaginal colonisation with Group B Streptococcus (GBS,
      Streptococcus agalactiae) at the time of delivery can cause vertical transmission
      to the neonate. GBS is the leading cause of sepsis, meningitis and pneumonia in
      the infants. Asymptomatic colonisation of the vagina with GBS varies with the
      geographical location. METHODS: This was a cross-sectional study conducted in
      2009 at Benazir Bhutto Hospital, Rawalpindi, Pakistan. Lower vaginal swabs were
      obtained from 200 pregnant women at the time of admission in the Gynaecology and
      Obstetrics Department for term, normal vaginal delivery and swabs from the skin
      of abdomen and ear canals of their respective neonates immediately after delivery
      were collected. Swabs were inoculated on blood agar and incubated aerobically and
      on Group B Streptococcus agar (GBS agar) and incubated anaerobically in an
      anaerobic jar. Identification of GBS was made on the basis of colonial morphology
      (beta-haemolytic colonies on blood agar and orange pigmented colonies on GBS
      agar), Gram stain, catalase test and conformation was done by means of latex
      agglutination tests. RESULTS: A GBS carriage rate of 8.5% among pregnant women
      before delivery and an acquisition rate of 53% on the abdominal skin and 18% in
      the ear canals by the neonates of colonised mothers were found. CONCLUSIONS: GBS
      colonisation in pregnant women and its transmission to the neonates is present in
      our population so GBS infections in the prenatal and neonatal period might not be
      uncommon in Pakistan, so routine screening should be carried out.

PMID- 22455290
TI  - Rapid confirmation of tuberculous meningitis in children by liquid culture media.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is an important and serious complication
      of tuberculosis (TB) related to high morbidity and mortality. Childhood TBM is a
      diagnostic dilemma as the clinical features are non-specific and cerebrospinal
      fluid (CSF) mycobacterial count is low. The diagnosis is made mostly on clinical
      grounds, CSF analysis and radiological findings and treatment is initiated before
      the culture results arrive. These non-specific rapid diagnostic tools may be
      misleading resulting in over diagnosis or misdiagnosis. The conventional way of
      establishing a definitive diagnosis of TBM is by solid-medium culture that
      requires 4-7 weeks which may often lead to injudicious exposure to hazards
      associated with anti-tuberculous therapy (ATT). METHODS: This study was carried
      out at the Microbiology department of University Of Health Sciences Lahore. The
      aim of this study was to assess the reliability of clinical features and CSF
      analysis in diagnosing childhood TBM by utilizing BACTEC Mycobacterial Growth
      Indicator Tube (MGIT) 960 system as a rapid confirmatory tool. It was an
      observational study that included 100 CSF samples from suspected paediatric TBM
      cases. After carrying out the biochemical and cytological analysis the samples
      were subjected to Ziehl-Neelsen (ZN) staining and inoculated onto MGIT 960
      system. The culture growths were tested for sensitivity to first line ATT.
      RESULTS: Of the 100 samples inoculated, only 14 yielded a growth, thus
      emphasizing unreliability of clinical criteria to diagnose TBM. CSF biochemistry
      was found insignificant for the diagnosis of TBM (p = 2.260). The CSF cytology,
      however, was found significant for diagnosing TBM (p = 0.001). CONCLUSIONS: The
      study showed that BACTEC MGIT 960 can be effectively used as a rapid diagnostic
      tool for the diagnosis of extra pulmonary tuberculosis.

PMID- 22455291
TI  - Audit of sharp weapon deaths in metropolis of Karachi--an autopsy based study.
AB  - BACKGROUND: Sharp weapons are one of the most violent and abhorrent means of
      deaths. This study assesses the frequency of sharp weapon deaths in Karachi.
      METHODS: This was a cross sectional study, and involves the deaths by sharp
      weapons autopsied in Karachi during Mar 2008-Feb 2009. RESULTS: This study
      reports that the frequency of sharp weapon deaths in Karachi is similar to some
      other studies conducted in different regions of Pakistan, yet it is very high as
      the population of Karachi is way more than any other metropolis of Pakistan. Our
      study reported that out of 2090 medico-legal deaths in Karachi during the study
      period, 91 deaths were due to sharp weapons, including 73 (80.2%) males and 18
      (19.8%) females. 100% of the deaths were homicides, so none were suicides. Deaths
      were more frequent in age group ranging from 20-39 years (59.3%). CONCLUSION:
      Sharp weapon deaths continue to be a means of quite a number of deaths in
      Karachi. Such violence depicts intolerant and frustrated nature of the citizens.

PMID- 22455292
TI  - Diagnostic accuracy of fine needle aspiration of thyroid nodule versus biopsy in
      thyroid lesions.
AB  - BACKGROUND: FNA biopsy of thyroid is a rapid, minimally invasive, and cost
      effective first line procedure in the evaluation of thyroid nodule. This study
      was conducted to evaluate the cytological accuracy, sensitivity and specificity
      of fine needle aspiration (FNA) of solitary thyroid nodules in correlation with
      post-surgical histological findings. METHODS: This retrospective study was
      carried out at Department of Pathology, Abbottabad International Medical College,
      Abbottabad from January 2009 to December 2010. A total of 81 patients with
      clinically palpable solitary thyroid nodule were included in the study. Thyroid
      function tests were initially performed followed by FNA of thyroid nodules later
      operated and histopathological examination was conducted on the excised nodules.
      FNA diagnoses were correlated with the histological findings. The accuracy,
      sensitivity and specificity of the procedure were determined. RESULTS: Out of 81
      cases, 5 (6.2%) were unsatisfactory and 76 cases were satisfactory for
      cytological evaluation. Cyto-histopathological correlation was carried out for
      these cases. The study showed a diagnostic accuracy of 93% with sensitivity and
      specificity rates of 75% and 96% respectively. Positive predictive value is 81%
      and negative predictive value is 95%. CONCLUSION: Fine needle aspiration (FNA)
      has evolved as an accurate and sensitive diagnostic tool for the initial
      screening of patients with thyroid nodules, and has reduced the need for
      unnecessary surgery.

PMID- 22455293
TI  - Percentage of CD4+ and CD8+ T-lymphocytes in blood of tuberculosis patients.
AB  - BACKGROUND: Tuberculosis is a fatal infectious disease, mainly caused by
      Mycobacterium tuberculosis. Spread of TB is controlled by cell-mediated immunity.
      Purpose of this study was to determine CD4+ and CD8+ T cell percentages in TB
      patients. METHODS: 77 subjects consisted of 39 patients of active tuberculosis
      and 37 normal healthy individuals were recruited for the study. Among patients,
      27 were at different stages of anti-tuberculous therapy while rests of the
      patients were not taking treatment. Sixteen patients were sputum positive for AFB
      while other patients were sputum negative for AFB. T cells percentages were
      determined by flow cytometer. RESULTS: In TB patients CD4+ and CD8+ T cells
      percentages were 34.4 +/- 9.8 and 32.0 +/- 9.8 while in controls these were 37.1
      +/- 6.9 and 30.2 +/- 7.2 respectively but the difference was statistically
      insignificant. CD4+ T cell percentage in newly diagnosed TB patients was 28.8 +/-
      8.7 while it was 37.9 +/- 8.9 in TB patients who were on therapy and difference
      was statistically significant whereas difference in CD8+ T-cell percentages was
      statistically insignificant. A negative correlation between CD8+ T-cells
      percentage and the duration of ATT was found. CONCLUSION: CD4+ and CD8+ T-cells
      percentages may help to find out the immune status of TB patients before and
      after the completion of ATT.

PMID- 22455295
TI  - Hypoxic ischemic encephalopathy in neonates.
AB  - BACKGROUND: Birth anoxia remains an important cause of mortality and morbidity in
      neonates. Hypoxia/ischemia can lead to permanent brain damage and also affects
      other tissues of the body. It results from lack of oxygen before, during or after
      birth. The study was designed to assess the risk factors of birth asphyxia,
      common presentations and association of Apgar score with grades of hypoxic
      ischemic encephalopathy. METHODS: The study is descriptive, prospective and
      carried out in the Paediatric Department of Ayub Teaching Hospital, Abbottabad
      from September 2007 till September 2008. A total number of 181 neonates (144
      males and 37 females) who showed the neurological signs of hypoxic-ischemic
      encephalopathy were included in the study. Maternal history was taken, Apgar
      scoring was done and neurological grading was done for the assessment of brain
      damage. RESULTS: Out of 181 neonates 77.9% were full term, 8.8% were premature,
      5.2% were having intra uterine growth retardation and 6.1% were post mature.
      38.7% were diagnosed as having grade-3, 38.7% as grade-2 and 22.6% as grade-1
      encephalopathy. Mortality due to hypoxic ischemic encephalopathy in our unit was
      16%. 52.5% of the mothers were primigravida, 50% of the multigravid mothers had
      history of perinatal deaths, and 6.1% had ante-natal examination. Antenatal
      factors like lack of antenatal examinations, toxaemia of pregnancy and prolonged
      labour were major contributors to the mortality of neonates. CONCLUSION:
      Primigravid mothers, maternal anaemia, lack of antenatal examination, toxaemia of
      pregnancy and prolonged labour were the major contributors to the hypoxic
      ischemic encephalopathy. Early recognition of the risk factors and public health
      awareness needs to be addressed. Improvements in maternal health and regular
      antenatal checkups should be emphasised.

PMID- 22455294
TI  - Factors for inaccessibility of antenatal care by women in Sindh.
AB  - BACKGROUND: Antenatal care is important for pregnant women. By good antenatal
      care many complications of pregnancy can be prevented and lives can be saved.
      This study was carried out to find out the reasons of not utilising antenatal
      care, knowledge about dangerous signs and symptoms of pregnancy, and diet in
      women receiving and not receiving antenatal care. METHODS: This descriptive study
      was conducted at Department of Obstetrics and Gynaecology, Liaquat University
      Hospital, Hyderabad Pakistan from February 2007 to October 2007. A total of 134
      women who came for delivery were included in the study. Out of these, 71 women
      had received antenatal care while 63 did not receive antenatal care. After taking
      informed consent, women were interviewed regarding demographic data, reason of
      not utilising antenatal care, knowledge about diet and dangerous signs and
      symptoms of pregnancy. RESULTS: Twenty-eight (44.44%) women did not receive
      antenatal care because the facility was far away from home, 10 (15.87%) said that
      transport was not available. Tetanus toxoid coverage was higher among women who
      received antenatal care (p < 0.0001). Women who received antenatal care were more
      aware of the dangerous signs and symptoms of pregnancy than women who did not
      receive antenatal care. CONCLUSION: Most common reason of not utilising antenatal
      care was that facility was far away from there home. Women who received antenatal
      care were not anaemic and had received tetnus toxoid vaccination. They knew more
      about diet and dangerous sign and symptoms of pregnancy than women who had not
      received antenatal care.

PMID- 22455296
TI  - Outcome of transurethral resection of prostate in clinical benign prostatic
      hyperplasia.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is a condition in which the
      prostate gland becomes enlarged. Some men with enlarged prostate glands may
      experience symptoms while some may have few symptoms. Symptomatic improvement
      determines the successful outcome of surgical procedure of TURP for clinical BPH
      patients. Objectives of this study were to assess the outcome of transurethral
      resection of prostate (TURP) in clinical BPH with the help of International
      Prostate Symptom Score (IPSS). METHODS: This was descriptive case series study
      conducted at the Department of Urology, Liaquat University of Medical and Health
      Sciences, Jamshoro from November 2009 to April 2010. All patients who underwent
      TURP for clinical BPH were included in the study. Their preoperative IPSS was
      done by asking irritative and obstructive symptoms. IPSS was calculated for
      patients who presented with urinary retention by asking lower urinary tract
      symptoms before urinary retention. Each symptom carried a score of 0-5, and the
      total score was 35. After the TURP, IPSS was calculated on 1st follow-up visit
      after 6 weeks and 2nd follow-up visit after 12 weeks. Outcome, was considered
      favourable if there was mild grade (IPSS < 7) on 12th week after TRUP. RESULTS:
      Total of 70 patients of clinical BPH were included in study. Mean age of the
      patients was 63.1 +/- 3.0 yrs. Outcome of transurethral resection of prostate was
      found to be favourable in 81.4% after 6 weeks in 1st follow-up visit and in 62
      (88.6%) patients after 12 weeks in second follow-up visit. Preoperatively mean
      IPSS was 22.5 and postoperatively mean IPSS was 6.5. CONCLUSION: TURP is an
      effective and gold standard surgical treatment option in the clinical BPH
      patients.

PMID- 22455297
TI  - In vitro antifungal sensitivity of fluconazole, clotrimazole and nystatin against
      vaginal candidiasis in females of childbearing age.
AB  - BACKGROUND: Vaginal candidiasis is the most common infection of females. A large
      variety of antifungal drugs are used for treatment. The objective of this study
      was isolation and identification of Candida from high vaginal swabs and in vitro
      antifungal activity of Clotrimazole, Fluconazole and Nystatin against Candida.
      METHODS: Two hundred and fifty high vaginal swabs were collected from females
      reporting at different hospitals of Karachi. Wet mount was performed to observe
      the budding cells of Candida. Vaginal swabs were cultured on Sabouraud's dextrose
      agar with added antibiotics. Plates were incubated at room temperature for seven
      days. Chlamydospores of Candida albicans were identified on corn meal agar.
      Species of Candida were identified on Biggy agar. In vitro antifungal activity of
      Clotrimazole, Fluconazole and Nystatin was performed by MIC (Minimum inhibitory
      concentration), well diffusion method and disc diffusion method. RESULTS: Out of
      250 high vaginal swabs, Candida species were isolated in 100 (40%) of cases. Out
      of 100, C. albican 30 (30%), C. tropicalis 21 (21%), C. parapsillosis 10 (10%),
      C. parakrusi 8 (8%), C. glabrata 8 (8%), C. krusei 3 (3%) were isolated. In vitro
      antifungal activity indicated Clotrimazole (MIC 16 and 8 microg/ml) effective
      against 68 (70%) of Candida SPP, Fluconazole (MIC 64 and 32 microg/ml) effective
      against 29 (36.2%) and Nystatin disc (100 units) was 51 (63.5%) effective.
      CONCLUSION: C. albicans was mainly isolated. Clotrimazole was more effective as
      compared to Fluconazole and Nystatin. Antifungal susceptibility testing should be
      determined before therapy to avoid treatment failures.

PMID- 22455298
TI  - Assessment Driven Integrated Learning (ADIL): Assessment Directed Medical
      Education (ADME) curriculum.
AB  - Assessment has been shown to drive learning. For assessment to drive learning in
      the right direction, it needs to fulfil certain criteria including reliability,
      validity, educational impact, feasibility, acceptability to stakeholders, cost
      effectiveness etc. Assessment has the greatest effect as a driving force in
      learning if it is authentic, context relevant and samples widely. In this paper,
      we present a new curriculum design and a model for experiential learning through
      assessment. We call it Assessment Directed Medical Education (ADME) Curriculum
      using Assessment Driven Integrated Learning (ADIL). In this model, we propose a
      cent percent rightest shift in the curriculum design and learning strategy by
      using assessment as the sole tool to a self-directed learning process through
      supervised simulated and real-patient encounters testing competencies in
      cognitive, psychomotor and affective domains in an integrated approach utilising
      key resources for active learning. It is presumed that, this will, in the long
      term improve health care delivery by producing competent healthcare professionals
      that have learned through direct student-'patient' encounters from day one of
      their medical education and are competent in making professional judgments,
      exhibit appropriate skills and behaviours.

PMID- 22455299
TI  - Family medicine in undergraduate medical curriculum: a cost-effective approach to
      health care in Pakistan.
AB  - BACKGROUND: Shifa College of Medicine introduced a two-week rotation in Family
      Medicine for their third-year medical students in 2008. The purpose of this study
      was to determine what impact it made on students and how many would consider
      becoming Family Physicians in future. METHODS: A questionnaire-based prospective
      study conducted at Shifa College of Medicine, Islamabad during academic year
      2008. RESULTS: A total of 46 students rotated in Family Medicine throughout the
      academic year-2008. Fifteen students were aware of Family Medicine as a specialty
      prior to starting their rotation, and only 3 expressed an interest to pursue
      Family Medicine as a future career. At the start of the rotation only 15 students
      were able to give correct definition of Family Medicine and on questioning
      whether it should be a part of the undergraduate curriculum, only 24 answered yes
      while the rest were unsure. After the rotation, a significant number of students
      (37%; p < 0.01) considered having a career in Family Practice, and 80% (n = 37)
      were able to give correct definition of Family Medicine as a humanistic approach
      of medicine with aim to prevent, treat and rehabilitate. About its utility in the
      undergraduate curriculum, 44 (96%) students believed it should be a regular
      feature in their curriculum, while 30 (65%) students agreed that their outlook
      towards patient care had changed. When asked what they learnt most during the
      rotation, students quoted empathy and development of communication skills.
      CONCLUSION: Family medicine rotation as part of undergraduate medical curriculum
      may help in fostering an interest among medical students in this newly emerging
      subspecialty which could have a profound effect on delivery of quality health
      care in this country.

PMID- 22455300
TI  - Community mental health in Peshawar, the need to reform.
AB  - Community mental health is a neglected field in many developing countries
      including Pakistan. Common mental disorders are high in prevalence, particularly
      in women. Community mental health services are lacking in Peshawar, which faces a
      number of challenges owing to sociopolitical instability. The aim of this
      literature review is to evaluate and interpret current research relevant to
      community mental health reform, including a review of the evidence regarding
      community mental health service. A selected review of published literature was
      undertaken using the PubMed, PsychINFO and Cochrane Database of Systematic
      Reviews databases. The intervention studies included in this review demonstrate
      that community based mental health services closely aligned with primary care
      services have the potential to facilitate improvements in access to care and also
      improvements in mental health outcomes. It concludes that lack of proper mental
      health policy and non-integration of mental health in primary health care
      adversely affects the outcome of mental health progress in community.

PMID- 22455301
TI  - Gated MIBI myocardial SPECT showing balanced ischemia and global hypokinesia in
      patient having thrombus in basal segment of dominant circumflex system blocking
      both left anterior descending and circumflex artery.
AB  - Myocardial perfusion imaging (MPI) is a powerful diagnostic and prognostic tool
      for evaluating coronary artery disease (CAD). Gating myocardial perfusion gives
      important diagnostic and prognostic information. This 43 years old patient was
      referred for cardiac scan. Exercise stress test showed > 2 mm horizontal ST
      segment depression. Cardiac scan was normal except for left ventricular cavity
      dilatation on stress images. Gated images showed global hypokinesia and increased
      end-diastolic volume. Patient was suspected to have balanced ischemia and was
      referred for Angiography. Angiography showed total occlusion with no flow in
      proximal Left Anterior Descending Artery and distal circumflex artery. It is very
      important to evaluate symptomatic patients and patients with risk factors
      carefully with normal myocardial perfusion scan.

PMID- 22455302
TI  - Rapunzel syndrome.
AB  - A trichobezoar may be confined to the stomach or unusually it may extend from
      stomach to the small intestine or beyond when it is labelled as Rapunzel
      syndrome. Bezoars are concretions in the gastrointestinal tract that increase in
      size by continuous accumulation of non-absorbable food or fibre. Most bezoars in
      children are trichobezoars from swallowed hair. Repunzal syndrome is an uncommon
      condition in children with less than 40 cases reported. We present a case of an 8
      year old girl with Rapunzel syndrome. She presented with vague abdominal pain and
      epigastric fullness of one year duration. On investigation she was found to have
      a trichobezoar. At laparotomy a large dark foul smelling trichobezoar that
      occupied the stomach, duodenum and proximal jejunum was removed via gastrostomy.

PMID- 22455303
TI  - Aluminium phosphide poisoning: a case report.
AB  - This paper reports the case of a family in which three children were presented at
      Emergency Room (ER) with poisoning after the use of a pesticide at home.
      Initially, the cases were managed as routine cases of organophosphorus poisoning;
      however, the death of two children made the health team members realise that the
      poison's effects were delayed and devastating. Later, the compound was identified
      as Aluminium Phosphide (ALP), and the life of the last surviving child in the
      family was saved.

PMID- 22455304
TI  - Lindane toxicity in a 7 year old boy.
AB  - Lindane (gamma-benzene hexachloride) is widely used as a scabicide by general
      practitioners and dermatologists in Pakistan. We present a case of a 7 year old
      boy who had suffered from scabies 1 week ago, for which he was prescribed lindane
      along with other medications by a general practitioner. After 3 application of
      lindane the child began to experience Grand mal seizures, ataxia, weakness,
      incoordination and severe burning paresthesias. Lindane is known to cause
      neurotoxicity and for this it has been recommended as a 2nd line treatment for
      scabies by FDA.

PMID- 22455305
TI  - Author's qualities essential for a good scientific publication.

PMID- 22455306
TI  - Imaging the material properties of bone specimens using reflection-based infrared
      microspectroscopy.
AB  - Fourier transform infrared microspectroscopy (FTIRM) is a widely used method for
      mapping the material properties of bone and other mineralized tissues, including
      mineralization, crystallinity, carbonate substitution, and collagen cross
      linking. This technique is traditionally performed in a transmission-based
      geometry, which requires the preparation of plastic-embedded thin sections,
      limiting its functionality. Here, we theoretically and empirically demonstrate
      the development of reflection-based FTIRM as an alternative to the widely adopted
      transmission-based FTIRM, which reduces specimen preparation time and broadens
      the range of specimens that can be imaged. In this study, mature mouse femurs
      were plastic-embedded and longitudinal sections were cut at a thickness of 4 MUm
      for transmission-based FTIRM measurements. The remaining bone blocks were
      polished for specular reflectance-based FTIRM measurements on regions immediately
      adjacent to the transmission sections. Kramers-Kronig analysis of the reflectance
      data yielded the dielectric response from which the absorption coefficients were
      directly determined. The reflectance-derived absorbance was validated empirically
      using the transmission spectra from the thin sections. The spectral assignments
      for mineralization, carbonate substitution, and collagen cross-linking were
      indistinguishable in transmission and reflection geometries, while the
      stoichiometric/nonstoichiometric apatite crystallinity parameter shifted from
      1032/1021 cm(-1) in transmission-based to 1035/1025 cm(-1) in reflection-based
      data. This theoretical demonstration and empirical validation of reflection-based
      FTIRM eliminates the need for thin sections of bone and more readily facilitates
      direct correlations with other methods such as nanoindentation and quantitative
      backscatter electron imaging (qBSE) from the same specimen. It provides a unique
      framework for correlating bone's material and mechanical properties.

PMID- 22455307
TI  - High-throughput quantitative analysis of total N-glycans by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Accurate and reproducible quantification of glycans from protein drugs has become
      an important issue for quality control of therapeutic proteins in
      biopharmaceutical and biotechnology industries. Mass spectrometry is a promising
      tool for both qualitative and quantitative analysis of glycans owing to mass
      accuracy, efficiency, and reproducibility, but it has been of limited success in
      quantitative analysis for sialylated glycans in a high-throughput manner. Here,
      we present a solid-phase permethylation-based total N-glycan quantitative method
      that includes N-glycan releasing, purification, and derivatization on a 96-well
      plate platform. The solid-phase neutralization enabled us to perform reliable
      absolute quantification of the acidic N-glycans as well as neutral N-glycans from
      model glycoproteins (i.e., chicken ovalbumin and porcine thyroglobulin) by only
      using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS). Furthermore, low-abundance sialylated N-glycans from
      human serum prostate specific antigen (PSA), an extremely valuable prostate
      cancer marker, were initially quantified, and their chemical compositions were
      proposed. Taken together, these results demonstrate that our all-inclusive glycan
      preparation method based on a 96-well plate platform may contribute to the
      precise and reliable qualitative and quantitative analysis of glycans.

PMID- 22455309
TI  - Lives saved from malaria prevention in Africa--evidence to sustain cost-effective
      gains.
AB  - Lives saved have become a standard metric to express health benefits across
      interventions and diseases. Recent estimates of malaria-attributable under-five
      deaths prevented using the Lives Saved tool (LiST), extrapolating effectiveness
      estimates from community-randomized trials of scale-up of insecticide-treated
      nets (ITNs) in the 1990s, confirm the substantial impact and good cost
      effectiveness that ITNs have achieved in high-endemic sub-Saharan Africa. An even
      higher cost-effectiveness would likely have been found if the modelling had
      included the additional indirect mortality impact of ITNs on preventing deaths
      from other common child illnesses, to which malaria contributes as a risk factor.
      As conventional ITNs are being replaced by long-lasting insecticidal nets and
      scale-up is expanded to target universal coverage for full, all-age populations
      at risk, enhanced transmission reduction may--above certain thresholds--enhance
      the mortality impact beyond that observed in the trials of the 1990s. On the
      other hand, lives saved by ITNs might fall if improved malaria case management
      with artemisinin-based combination therapy averts the deaths that ITNs would
      otherwise prevent.Validation and updating of LiST's simple assumption of a
      universal, fixed coverage-to-mortality-reduction ratio will require enhanced
      national programme and impact monitoring and evaluation. Key indicators for time
      trend analysis include malaria-related mortality from population-based surveys
      and vital registration, vector control and treatment coverage from surveys, and
      parasitologically-confirmed malaria cases and deaths recorded in health
      facilities. Indispensable is triangulation with dynamic transmission models,
      fitted to long-term trend data on vector, parasite and human populations over
      successive phases of malaria control and elimination.Sound, locally optimized
      budget allocation including on monitoring and evaluation priorities will benefit
      much if policy makers and programme planners use planning tools such as LiST -
      even when predictions are less certain than often understood. The ultimate
      success of LiST for supporting malaria prevention may be to prove its linear
      predictions less and less relevant.

PMID- 22455310
TI  - Effect of acute endurance and resistance exercise on endocrine hormones directly
      related to lipolysis and skeletal muscle protein synthesis in adult individuals
      with obesity.
AB  - In subjects with obesity, the implementation of long-term exercise intervention
      increases lean tissue mass and lowers adipose tissue mass. However, data indicate
      a blunted lipolytic response, and/or skeletal muscle protein synthesis, when
      subjects with obesity are exposed to acute endurance or resistance exercise,
      respectively. Therefore, subjects with obesity seem to display a suboptimal
      physiological response to acute exercise stimuli. It might be hypothesized that
      hormonal disturbances contribute, at least in part, to these abnormal
      physiological reactions in the obese. This review discusses the impact of acute
      endurance and resistance exercise on endocrine hormones directly related to
      lipolysis and/or skeletal muscle protein synthesis (insulin, [nor]epinephrine,
      cortisol, growth hormone, testosterone, triiodothyronine, atrial natriuretic
      peptide, insulin-like growth factor-1), as well as the impact of long-term
      endurance and resistance exercise intervention on these hormonal responses to
      acute endurance and resistance exercise. In the obese, some endocrinological
      disturbances during acute endurance and resistance exercise have been identified:
      a blunted blood growth hormone, atrial natriuretic peptide and epinephrine
      release, and greater cortisol and insulin release. These hormonal disturbances
      might contribute to a suppressed lipolytic response, and/or suppressed skeletal
      muscle protein synthesis, as a result of acute endurance or resistance exercise,
      respectively. In subjects with obesity, the impact of acute endurance and
      resistance exercise on other endocrine hormones (norepinephrine, testosterone,
      triiodothyronine, insulin-like growth factor-1) remains elusive. Furthermore,
      whether long-term endurance and resistance exercise intervention might reverse
      these hormonal disturbances during acute endurance and resistance exercise in
      these individuals remains unknown.

PMID- 22455311
TI  - Pathological vertebral fracture after stereotactic body radiation therapy for
      lung metastases. Case report and literature review.
AB  - BACKGROUND: Stereotactic body radiation therapy (SBRT) is a radiation technique
      used in patients with oligometastatic lung disease. Lung and chest wall
      toxicities have been described in the patients but pathological vertebral
      fracture is an adverse effect no reported in patients treated with SBRT for lung
      metastases. CASE PRESENTATION: A 68-year-old woman with the diagnosis of a
      recurrence of a single lung metastatic nodule of urothelial carcinoma after third
      line of chemotherapy. The patient received a hypo-fractionated course of SBRT.A
      3D-conformal multifield technique was used with six coplanar and one non-coplanar
      statics beams. A total dose of 48 Gy in three fractions over six days was
      prescribed to the 95% of the CTV. Ten months after the SBRT procedure, a CT scan
      showed complete response of the metastatic disease without signs of radiation
      pneumonitis. However, rib and vertebral bone toxicities were observed with the
      fracture-collapse of the 7th and 8th vertebral bodies and a fracture of the 7th
      and 8th left ribs. We report a unique case of pathological vertebral fracture
      appearing ten months after SBRT for an asymptomatic growing lung metastases of
      urothelial carcinoma. CONCLUSION: Though SBRT allows for minimization of normal
      tissue exposure to high radiation doses SBRT tolerance for vertebral bone tissue
      has been poorly evaluated in patients with lung tumors. Oncologists should be
      alert to the potential risk of fatal bone toxicity caused by this novel
      treatment. We recommend BMD testing in all woman over 65 years old with clinical
      risk factors that could contribute to low BMD. If low BMD is demonstrated, we
      should carefully restrict the maximum radiation dose in the vertebral body in
      order to avoid intermediate or low radiation dose to the whole vertebral body.

PMID- 22455312
TI  - Synthesis, biological evaluation, and structure-activity relationships of a novel
      class of apurinic/apyrimidinic endonuclease 1 inhibitors.
AB  - APE1 is an essential protein that operates in the base excision repair (BER)
      pathway and is responsible for >=95% of the total apurinic/apyrimidinic (AP)
      endonuclease activity in human cells. BER is a major pathway that copes with DNA
      damage induced by several anticancer agents, including ionizing radiation and
      temozolomide. Overexpression of APE1 and enhanced AP endonuclease activity have
      been linked to increased resistance of tumor cells to treatment with
      monofunctional alkylators, implicating inhibition of APE1 as a valid strategy for
      cancer therapy. We report herein the results of a focused medicinal chemistry
      effort around a novel APE1 inhibitor, N-(3-(benzo[d]thiazol-2-yl)-6-isopropyl
      4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)acetamide (3). Compound 3 and related
      analogues exhibit single-digit micromolar activity against the purified APE1
      enzyme and comparable activity in HeLa whole cell extract assays and potentiate
      the cytotoxicity of the alkylating agents methylmethane sulfonate and
      temozolomide. Moreover, this class of compounds possesses a generally favorable
      in vitro ADME profile, along with good exposure levels in plasma and brain
      following intraperitoneal dosing (30 mg/kg body weight) in mice.

PMID- 22455314
TI  - Overexpression of the gap junction protein Cx43 as found in diabetic foot ulcers
      can retard fibroblast migration.
AB  - Poor healing of DFUs (diabetic foot ulcers) is a major clinical problem that can
      be extremely debilitating and lead to lower limb amputation. In the normal acute
      wound, the Cx43 (connexin 43) gap junction protein is down-regulated at the wound
      edge as a precursor to cell migration and healing. In fibroblasts from the human
      chronic DFU wound edge there was a striking and significant 10-fold elevation of
      Cx43 protein, as well as a 6-fold increase in N-cadherin and a 2-fold increase in
      ZO-1 (zonular occludin-1), compared with unwounded skin. In streptozotocin
      diabetic rats, Cx43 was found to be up-regulated in intact dermal fibroblasts in
      direct proportion to blood glucose levels and increased 2-fold further in
      response to wounding of the skin. To mimic diabetes, NIH 3T3 fibroblasts were
      cultured under different concentrations of glucose or mannitol and Cx43 protein
      intercellular communication and migration rates were determined. Cultures of
      fibroblasts in very high (40 mM) glucose conditions showed significantly elevated
      Cx43 protein levels, as shown by immunostaining and Western blotting, and
      significantly increasing gap junctional communication, as shown by dye transfer.
      In scratch wound-healing assays, increased levels of Cx43 from high glucose
      resulted in repressed filopodial extensions and significantly slower migration
      rates than in either standard conditions (5.5 mM glucose) or the osmotic control
      of mannitol. Conversely, when glucose-induced Cx43 up-regulation was prevented
      with Cx43shRNA (Cx43 short-hairpin RNA) transduction, the fibroblasts extended
      long filopodia and migrated significantly faster. Cx43 protein was up-regulated
      in fibroblasts in DFUs as well as after high glucose exposure in culture which
      correlated with inhibition of fibroblast migration and is likely to contribute to
      impaired wound healing.

PMID- 22455313
TI  - P3-P3' residues flanking scissile bonds in factor VIII modulate rates of
      substrate cleavage and procofactor activation by thrombin.
AB  - Thrombin-catalyzed activation of factor VIII (FVIII) occurs through proteolysis
      at three P1 Arg residues: Arg(372) and Arg(740) in the FVIII heavy chain and
      Arg(1689) in the FVIII light chain. Cleavage at the latter two sites is
      relatively fast compared with cleavage at Arg(372), which appears to be rate
      limiting. Examination of the P3-P3' residues flanking each P1 site revealed that
      those sequences at Arg(740) and Arg(1689) are more optimal for thrombin cleavage
      than at Arg(372), suggesting these sequences may impact reaction rates.
      Recombinant FVIII variants were prepared with mutations swapping scissile bond
      flanking sequences in the heavy chain individually and in combination with a
      second swap or with a P1 point mutation. Rates of generation of A1 and A3-C1-C2
      subunits were determined by Western blotting and correlated with rates of
      cleavage at Arg(372) and Arg(1689), respectively. Rates of thrombin cleavage at
      Arg(372) were increased ~10- and ~3-fold compared with that of wild-type FVIII
      when it was replaced with P3-P3' residues flanking Arg(740) and Arg(1689),
      respectively, and these values paralleled increased rates of A2 subunit
      generation and procofactor activation. Positioning of more optimal residues
      flanking Arg(372) abrogated the need for initial cleavage at Arg(740) to
      facilitate this step. These results show marked changes in cleavage rates
      correlate with the extent of cleavage-optimal residues flanking the scissile bond
      and modulate the mechanism for procofactor activation.

PMID- 22455315
TI  - The effects of temperature on service employees' customer orientation: an
      experimental approach.
AB  - Numerous studies have demonstrated how temperature can affect perceptual,
      cognitive and psychomotor performance (e.g. Hancock, P.A., Ross, J., and Szalma,
      J., 2007. A meta-analysis of performance response under thermal stressors. Human
      Factors: The Journal of the Human Factors and Ergonomics Society, 49 (5), 851
      877). We extend this research to interpersonal aspects of performance, namely
      service employees' and salespeople's customer orientation. We combine ergonomics
      with recent research on social cognition linking physical with interpersonal
      warmth/coldness. In Experiment 1, a scenario study in the lab, we demonstrate
      that student participants in rooms with a low temperature showed more customer
      oriented behaviour and gave higher customer discounts than participants in rooms
      with a high temperature - even in zones of thermal comfort. In Experiment 2, we
      show the existence of alternative possibilities to evoke positive temperature
      effects on customer orientation in a sample of 126 service and sales employees
      using a semantic priming procedure. Overall, our results confirm the existence of
      temperature effects on customer orientation. Furthermore, important implications
      for services, retail and other settings of interpersonal interactions are
      discussed.    Practitioner Summary: Temperature effects on performance have
      emerged as a vital research topic. Owing to services' increasing economic
      importance, we transferred this research to the construct of customer
      orientation, focusing on performance in service and retail settings. The
      demonstrated temperature effects are transferable to services, retail and other
      settings of interpersonal interactions.

PMID- 22455316
TI  - Peak-peak repulsion in ion mobility spectrometry.
AB  - The space charge effect has an important role in instruments dealing with ion
      packets and charged particles in gas phase such as the mass spectrometer and ion
      mobility spectrometer (IMS). It has been shown that the space charge is partially
      responsible for peak broadening in IMS depending on the ion density. Here, we
      explore the effect of space charge on peak shifting in IMS. We show that the
      field created by a large peak influences the drift time of a neighboring small
      peak. An experimental method was introduced to accurately measure the effect of
      space charge between two peaks. In this method, a double pulse was applied to the
      shutter grid to create two closed ion packets with a given initial spacing. The
      final spacing was then measured at the collector through the separation of the
      two peaks. This study shows that space charge repulsion must be considered for
      accurate measurements of ion mobilities. The experiments were performed in both
      normal and inverse modes. A theoretical model was also proposed to describe the
      repulsion between two ion packets in IMS.

PMID- 22455318
TI  - Membraneless, room-temperature, direct borohydride/cerium fuel cell with power
      density of over 0.25 W/cm2.
AB  - The widespread adoption and deployment of fuel cells as an alternative energy
      technology have been hampered by a number of formidable technical challenges,
      including the cost and long-term stability of electrocatalyst and membrane
      materials. We present a microfluidic fuel cell that overcomes many of these
      obstacles while achieving power densities in excess of 250 mW/cm(2). The
      poisoning and sluggish reaction rate associated with CO-contaminated H(2) and
      methanol, respectively, are averted by employing the promising, high-energy
      density fuel borohydride. The high-overpotential reaction of oxygen gas at the
      cathode is supplanted by the high-voltage reduction of cerium ammonium nitrate.
      Expensive, ineffective membrane materials are replaced with laminar flow and a
      nonselective, porous convection barrier to separate the fuel and oxidant streams.
      The result is a Nafion-free, room-temperature fuel cell that has the highest
      power density per unit mass of Pt catalyst employed for a non-H(2) fuel cell, and
      exceeds the power density of a typical H(2) fuel cell by 50%.

PMID- 22455319
TI  - Production and release of selenocyanate by different green freshwater algae in
      environmental and laboratory samples.
AB  - In a previous study, selenocyanate was tentatively identified as a
      biotransformation product when green algae were exposed to environmentally
      relevant concentrations of selenate. In this follow-up study, we confirm
      conclusively the presence of selenocyanate in Chlorella vulgaris culture medium
      by electrospray mass spectrometry, based on selenium's known isotopic pattern. We
      also demonstrate that the observed phenomenon extends to other green algae
      (Chlorella kesslerii and Scenedesmus obliquus) and at least one species of blue
      green algae (Synechococcus leopoliensis). Further laboratory experiments show
      that selenocyanate production by algae is enhanced by addition of nitrate, which
      appears to serve as a source of cyanide produced in the algae. Ultimately, this
      biotransformation process was confirmed in field experiments where trace amounts
      of selenocyanate (0.215 +/- 0.010 ppb) were observed in a eutrophic, selenium
      impacted river with massive algal blooms, which consisted of filamentous green
      algae (Cladophora genus) and blue-green algae (Anabaena genus). Selenocyanate
      abundance was low despite elevated selenium concentrations, apparently due to
      suppression of selenate uptake by sulfate, and insufficient nitrogen
      concentrations. Finally, trace levels of several other unidentified selenium
      containing compounds were observed in these river water samples; preliminary
      suggestions for their identities include thioselenate and small organic Se
      species.

PMID- 22455317
TI  - Pan-genomic analysis of bovine monocyte-derived macrophage gene expression in
      response to in vitro infection with Mycobacterium avium subspecies
      paratuberculosis.
AB  - Mycobacterium avium subspecies paratuberculosis is the causative agent of Johne's
      disease, an intestinal disease of ruminants with major economic consequences.
      Infectious bacilli are phagocytosed by host macrophages upon exposure where they
      persist, resulting in lengthy subclinical phases of infection that can lead to
      immunopathology and disease dissemination. Consequently, analysis of the
      macrophage transcriptome in response to M. avium subsp. paratuberculosis
      infection can provide valuable insights into the molecular mechanisms that
      underlie Johne's disease. Here, we investigate pan-genomic gene expression in
      bovine monocyte-derived macrophages (MDM) purified from seven age-matched
      females, in response to in vitro infection with M. avium subsp. paratuberculosis
      (multiplicity of infection 2:1) at intervals of 2 hours, 6 hours and 24 hours
      post-infection (hpi). Differentially expressed genes were identified by comparing
      the transcriptomes of the infected MDM to the non-infected control MDM at each
      time point (adjusted P-value threshold <= 0.10). 1050 differentially expressed
      unique genes were identified 2 hpi, with 974 and 78 differentially expressed
      unique genes detected 6 and 24 hpi, respectively. Furthermore, in the infected
      MDM the number of upregulated genes exceeded the number of downregulated genes at
      each time point, with the fold-change in expression for the upregulated genes
      markedly higher than that for the downregulated genes. Inspection and systems
      biology analysis of the differentially expressed genes revealed an enrichment of
      genes involved in the inflammatory response, cell signalling pathways and
      apoptosis. The transcriptional changes associated with cellular signalling and
      the inflammatory response may reflect different immuno-modulatory mechanisms that
      underlie host-pathogen interactions during infection.

PMID- 22455320
TI  - The international CHANGE PAIN physician survey: does specialism influence the
      perception of pain and its treatment?
AB  - OBJECTIVES: This survey explores how physicians perceive chronic non-cancer pain,
      and examines their opinions on current treatment options. METHODOLOGY: The
      computer-based survey comprises a questionnaire that is completed by physicians,
      mostly at professional conferences and congresses, but also online. The focus is
      on pain specialists, primary care physicians and other specialists (such as
      neurologists and rheumatologists), to discover any differences in their approach
      to treating chronic non-cancer pain. RESULTS: No common understanding existed of
      where severe pain starts on an 11-point Numeric Rating Scale. Overall, two-thirds
      of respondents aim for treatment to reduce pain intensity to an NRS score of 2-4,
      with primary care physicians tending to aim for lower scores. All three groups
      considered reduction of pain to be the most important treatment goal, followed by
      quality of life. Asked to rank the most important factors when choosing an
      analgesic agent to treat severe, chronic non-cancer pain, respondents ranked
      efficacy first, tolerability second, and quality of life third. In each rank,
      more primary care physicians chose these options than in the specialist groups.
      More pain specialists used classical strong opioids often or very often - and for
      longer - than did physicians in the other two groups. Nausea/vomiting, bowel
      dysfunction and somnolence were ranked the first, second and third main reasons,
      respectively, for treatment failure with these agents. Over 90% of respondents
      used combination treatment rather than monotherapy to treat severe, chronic pain,
      but no fewer than 176 different combinations were cited. CONCLUSIONS: Pain
      reduction and improvement in quality of life are the most important treatment
      goals. Wide variation in treatment indicates that no single drug is particularly
      good for managing chronic pain, and suggests that current treatment is not
      evidence-based. Differences between the groups imply that first-line treatment is
      more cautious and conventional. The key limitations of this survey include its
      small sample size, informal implementation and lack of detail regarding the
      respondents surveyed.

PMID- 22455321
TI  - Introduction to the special issue on "The treatment of gender dysphoric/gender
      variant children and adolescents".

PMID- 22455322
TI  - Clinical management of gender dysphoria in children and adolescents: the Dutch
      approach.
AB  - The Dutch approach on clinical management of both prepubertal children under the
      age of 12 and adolescents starting at age 12 with gender dysphoria, starts with a
      thorough assessment of any vulnerable aspects of the youth's functioning or
      circumstances and, when necessary, appropriate intervention. In children with
      gender dysphoria only, the general recommendation is watchful waiting and
      carefully observing how gender dysphoria develops in the first stages of puberty.
      Gender dysphoric adolescents can be considered eligible for puberty suppression
      and subsequent cross-sex hormones when they reach the age of 16 years. Currently,
      withholding physical medical interventions in these cases seems more harmful to
      wellbeing in both adolescence and adulthood when compared to cases where physical
      medical interventions were provided.

PMID- 22455323
TI  - Psychological evaluation and medical treatment of transgender youth in an
      interdisciplinary "Gender Management Service" (GeMS) in a major pediatric center.
AB  - In 2007, an interdisciplinary clinic for children and adolescents with disorders
      of sex development (DSD) or gender identity disorder (GID) opened in a major
      pediatric center. Psychometric evaluation and endocrine treatment via pubertal
      suppressive therapy and administration of cross-sex steroid hormones was offered
      to carefully selected patients according to effective protocols used in Holland.
      Hembree et al.'s (2009) Guidelines for Endocrine Treatment of Transsexual Persons
      published by the Endocrine Society endorsed these methods. A description of the
      clinic's protocol and general patient demographics are provided, along with
      treatment philosophy and goals.

PMID- 22455324
TI  - From gender identity disorder to gender identity creativity: true gender self
      child therapy.
AB  - True gender self child therapy is based on the premise of gender as a web that
      weaves together nature, nurture, and culture and allows for a myriad of healthy
      gender outcomes. This article presents concepts of true gender self, false gender
      self, and gender creativity as they operationalize in clinical work with children
      who need therapeutic supports to establish an authentic gender self while
      developing strategies for negotiating an environment resistant to that self.
      Categories of gender nonconforming children are outlined and excerpts of a
      treatment of a young transgender child are presented to illustrate true gender
      self child therapy.

PMID- 22455325
TI  - A comprehensive program for children with gender variant behaviors and gender
      identity disorders.
AB  - This article describes a clinical program designed to address broadly defined
      mental health needs of children who experience stress related to not fitting into
      normative gender types and argues for the need for integrated services that
      address the spectrum of gender variance. An array of services useful to children
      and their families is proposed. The article describes the clinical population
      served, common clinical and social problems, and a rationale for the
      interventions provided.

PMID- 22455326
TI  - A developmental, biopsychosocial model for the treatment of children with gender
      identity disorder.
AB  - This article provides a summary of the therapeutic model and approach used in the
      Gender Identity Service at the Centre for Addiction and Mental Health in Toronto.
      The authors describe their assessment protocol, describe their current
      multifactorial case formulation model, including a strong emphasis on
      developmental factors, and provide clinical examples of how the model is used in
      the treatment.

PMID- 22455327
TI  - The dynamic development of gender variability.
AB  - We diagram and discuss theories of gender identity development espoused by the
      clinical groups represented in this special issue. We contend that theories of
      origin relate importantly to clinical practice, and argue that the existing
      clinical theories are under-developed. Therefore, we develop a dynamic systems
      framework for gender identity development. Specifically, we suggest that critical
      aspects of presymbolic gender embodiment occur during infancy as part of the
      synchronous interplay of caregiver-infant dyads. By 18 months, a transition to
      symbolic representation and the beginning of an internalization of a sense of
      gender can be detected and consolidation is quite evident by 3 years of age. We
      conclude by suggesting empirical studies that could expand and test this
      framework. With the belief that better, more explicit developmental theory can
      improve clinical practice, we urge that clinicians take a dynamic developmental
      view of gender identity formation into account.

PMID- 22455328
TI  - Supporting transgender children: new legal, social, and medical approaches.
AB  - The author, a lawyer who advocates for transgender children and youth, explores
      how clinical approaches to transgender children and youth are keeping pace with
      social and legal changes affecting these young people and with recent evidence
      suggesting that children are harmed by family and societal rejection as well as
      by attempts to change their gender identity or gender expression. The author
      urges providers and legal advocates to work with policymakers and the families of
      transgender children and youth to create a future in which these young people can
      reach their full potential and be embraced as fully equal, respected, and
      participating members of society.

PMID- 22455329
TI  - Thoughts on the nature of identity: how disorders of sex development inform
      clinical research about gender identity disorders.
AB  - Disorders of sex development (DSD), like gender dysphoria, are conditions with
      major effects on child sexuality and identity, as well as sexual orientation.
      Each may in some cases lead to change of gender from that assigned neonatally.
      These similarities-and the conditions' differences-provide a context for
      reviewing the articles in this issue about clinical approaches to children with
      gender dysphoria, in relation to assessment, intervention, and ethics.

PMID- 22455330
TI  - Apples to committee consensus: the challenge of gender identity classification.
AB  - The debate surrounding the inclusion of gender dysphoria/gender variant behavior
      (GD/GV) as a psychiatric diagnosis exposes many of the fundamental shortcomings
      and inconsistencies of our current diagnostic classification system. Proposals
      raised by the authors of this special issue, including basing diagnosis on cause
      rather than overt behavior, reclassifying GD/GV behavior as a physical rather
      than mental condition, and basing diagnosis on impairment or distress, offer some
      solutions but have limitations themselves given the available database. In
      contrast to most accepted psychiatric conditions where emphasis is placed on
      ultimately changing internal thoughts, feelings, and behaviors, consensus
      treatment for most GD/GV individuals, at least from adolescence onward, focuses
      on modifying the external body and external environment to maximize positive
      outcomes. This series of articles illustrating the diversity of opinions on when
      and if gender incongruence should be considered pathological reflects the
      relative lack of scientific indicators of disease in this area, similar to many
      other domains of mental functioning.

PMID- 22455331
TI  - Listening to children imagining gender: observing the inflation of an idea.
AB  - Using three of the clinical articles in this special issue of the Journal of
      Homosexuality as examples, the author attempts to show how their views of gender
      may influence clinicians' conceptualizations and treatment choices in response to
      children diagnosed with gender identity disorder (GID), or gender dysphoria. In
      particular the author argues that the belief that gender is a psychophysiological
      entity that is organismic and transhistorical, that is, the view known lately as
      essentialism, promotes more invasive interventions (e.g., endocrinological and
      surgical) and mistakenly deemphasizes psychological therapies as a clinical
      response to the suffering of trans children. He tries to show that the drawbacks
      of essentialism and its correlated treatment approaches are twofold, that a) they
      promote treatments with insufficient attention to our limited knowledge regarding
      their safety and efficacy, and b) they advance a reified differentiation of the
      genders that is politically problematic. The author suggests that a better
      response to trans children would be one that emphasizes the child's broadly
      subjective role in his or her construction of transgressive, gender-related
      psychological and interpersonal phenomena (both painful and not), thus, offering
      a deeper validation for trans children's challenges to our gender system.

PMID- 22455332
TI  - Commentary on the treatment of gender variant and gender dysphoric children and
      adolescents: common themes and ethical reflections.
AB  - This commentary offers preliminary ethical reflections on the range of treatments
      for gender variant and gender dysphoric children, adolescents, and young adults
      described in the preceding five clinical articles. After clarifying the
      terminology used to discuss these issues, this commentary reviews several common
      themes of the clinical articles. Focusing on ethical values of informed consent,
      full disclosure, the minimization or avoidance of harm, and the maximization of
      life options, the commentary expresses concerns about various treatment options
      endorsed by some of the articles. In particular, this commentary focuses on how
      these practices problematically reproduce social prejudices and stereotypes and
      how they fail to acknowledge and embrace the multiple pathways for expressing
      one's gender. It also compares and contrasts the ethical issues related to gender
      variant and gender dysphoric youths and youths who identify as lesbian, gay,
      bisexual, or queer.

PMID- 22455333
TI  - Gender dysphoric/gender variant (GD/GV) children and adolescents: summarizing
      what we know and what we have yet to learn.
AB  - The optimal approach to treating minors with gender dysphoria/gender variance
      (GD/GV) is much more controversial than treating these phenomena in adults. This
      is because children have limited capacity to participate in decision making
      regarding their own treatment, and even adolescents have no legal ability to
      provide informed consent. Minors must, therefore, depend on parents or other
      caregivers to make treatment decisions on their behalf, including those that will
      influence the course of their lives in the long term. Presently, the highest
      level of evidence available for selecting among the various approaches to
      treatment is best characterized as "expert opinion." Yet, opinions vary widely
      among experts and are influenced by theoretical orientation and assumptions and
      beliefs regarding the origins of gender identity, as well as its perceived
      malleability at particular stages of development. This article outlines some of
      the more salient points raised by the clinicians who treat GD/GV and their
      discussants. This article summarizes what the editors believe is known and what
      has yet to be learned about minors with GD/GV, their families, their treatment,
      and their surrounding cultures.

PMID- 22455334
TI  - Safety precautions in Mohs micrographic surgery for patients with known blood
      borne infections: a survey-based study.
AB  - PURPOSE: A survey-based study was conducted to gather expert experience on safety
      procedures used when performing Mohs micrographic surgery (MMS) on patients with
      known infectious hepatitis or human immunodeficiency virus (HIV). METHODS: Six
      hundred eighty-four fellowship-trained Mohs surgeons were surveyed to examine the
      types of safety protocols used when treating patients with known infectious
      hepatitis or HIV and the frequency of exposure injuries to laboratory and
      surgical personnel from these patients. RESULTS: One hundred eighty-eight (27.5%)
      surveys were collected; 64.7% of respondents reported at least one exposure
      injury to surgical or laboratory personnel in the past year, and 4.8% reported
      exposure from a patient with known hepatitis or HIV infection. Risk of reporting
      at least one injury from a patient with known infection within the past year was
      significantly less when also reporting disposal of the ink applicator after each
      use (relative risk [RR] = 0.109) and greater when employing laboratory personnel
      with no medical education or background (RR = 3.857). No exposures were reported
      from respondents using blunt skin hooks, safety scalpels, safety syringes, smoke
      evacuators, a separate ink supply, or 24-hour formalin fixation. CONCLUSION:
      Although firm associations cannot be made from this study, the data suggest that
      certain measures may help to reduce the rate of exposure injuries in MMS.

PMID- 22455335
TI  - Genetic polymorphisms in MMP 2, 9 and 3 genes modify lung cancer risk and
      survival.
AB  - BACKGROUND: Matrix metalloproteases (MMPs) are proteolytic enzymes that
      contribute to all stages of tumour progression, including the later stages of
      invasion and metastasis. Genetic variants in the MMP genes may influence the
      biological function of these enzymes and change their role in carcinogenesis and
      progression. We have investigated the association between the -735 C/T, the -1171
      5A/6A, and the -1562 C/T polymorphisms in the MMP2, MMP3 and MMP9 genes,
      respectively, and the risk and survival of lung cancer. METHODS: The case-control
      study includes 879 lung cancer patients and 803 controls from a Caucasian
      population in Spain (CAPUA study). Genotypes were determined by PCR-RFLP. Odds
      ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional
      logistic regression. The Kaplan-Meier method, long-rank test and Cox's were used
      for the survival analysis. RESULTS: The MMP9 -1562 T/T genotype was associated
      with a statistically significant decreased risk of developing lung cancer (OR =
      0.23; 95% CI: 0.06-0.85), whereas no association was found for the MMP2 -735 C/T
      and MMP3 -1171 5A/6A polymorphisms. The MMP2 -735 T/T genotype was statistically
      significantly associated with a decreased survival in non-small cell lung cancer
      (NSCLC) patients, identified as an independent prognosis factor of survival
      (hazard ratio (HR) = 1.79; 95% CI: 1.00-3.20). In contrast, no association was
      found between the MMP3 -1171 5A/6A and the MMP9 -1562 C/T polymorphisms and
      survival. CONCLUSIONS: These findings support the hypothesis that the MMP9 -1562
      C/T polymorphism is associated with a protective effect against the development
      of lung cancer and suggest that the MMP2 -735 C/T polymorphism modify the length
      of survival in NSCLC patients.

PMID- 22455336
TI  - Protein segregation between dividing hematopoietic progenitor cells in the
      determination of the symmetry/asymmetry of cell division.
AB  - In the present study, we investigated how the symmetry/asymmetry of cell division
      in mitotic CD34(+) cells can be evaluated by determining the plane of cell
      division and the potential distribution of proteins between daughter cells. The
      orientation of the mitotic spindle is dependent upon the positioning of the
      centrosomes, which determine the plane of cell division and the sharing of
      proteins. If the functions of unequally shared proteins are relevant to the
      kinetics of cell division, they could determine whether the daughter cells
      undergo self-renewal or differentiation. The kinetic function of the proteins of
      interest was investigated using a colony-replating assay and carboxyfluorescein
      succinimidyl ester (CFSE) staining. We used Notch/Numb as a model system, since
      they have a role in balancing symmetric/asymmetric divisions. Mitotic cells were
      examined microscopically and centrosomal markers gamma-tubulin/pericentrin were
      used with activated Notch-1 and Numb. We monitored the first crucial divisions by
      CFSE staining and found an inverse relationship between activated Notch and Numb
      expression, suggesting a reciprocal regulation. We suggest that the
      subpopulations expressing activated Notch or Numb have different cell fates. To
      determine the influence of Notch signaling on progenitor cell self-renewal, we
      used the gamma-secretase inhibitor N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S
      phenylglycine t-Butyl ester (DAPT). DAPT influences self-renewal/differentiation
      outcome by affecting the frequency of symmetric renewal divisions without
      affecting the rate of divisions. Overall, the purpose of this study was to
      establish a cellular system for predicting the symmetry/asymmetry of
      hematopoietic progenitor divisions at the level of centrosomes and protein
      distribution and to investigate the influence of these proteins on progenitor
      cell kinetics.

PMID- 22455337
TI  - Synthesis and characterization of a disulfide reporter molecule for enhancing pH
      measurements based on surface-enhanced Raman scattering.
AB  - In this paper, we describe the synthesis and characterization of 2,5
      dimercaptobenzoic acid as a novel pH-sensitive disulfide reporter molecule for
      surface-enhanced Raman scattering (SERS) capable of inducing the controlled
      aggregation of gold (Au) colloids in solution without the addition of salts.
      While weak acids have been shown to yield some pH sensitivity as reporter
      molecules for SERS measurements, the reproducibility and signal strength of
      nanoparticle probes based on such molecules can vary greatly. This limited
      reproducibility depends greatly on the salt-induced aggregation of the colloidal
      nanoprobes, which is required in order to obtain SERS signals strong enough to
      probe individual clusters. This complicates their use in live cell sensing
      applications. We show that our approach results in primarily bridged
      nanoparticles comprising a pH-sensitive nanoprobe that can quantify accurately pH
      values well below 5.5. The robustness and sensitivity of this system makes it a
      powerful tool for measuring pH values on the nanoscale under in vitro conditions.

PMID- 22455338
TI  - Polymer chain length effects on fibroblast attachment on nylon-3-modified
      surfaces.
AB  - Nylon-3 polymers have a polyamide backbone reminiscent of that found in proteins
      (beta- vs alpha-amino acid residues, respectively), which makes these materials
      interesting for biological applications. Because of the versatility of the ring
      opening polymerization process and the variety of beta-lactam starting materials
      available, the structure of nylon-3 copolymers is highly amenable to alteration.
      A previous study showed that relatively subtle changes in the structure or ratio
      of hydrophobic and cationic subunits that comprise these polymers can result in
      significant changes in the ability of nylon-3-bearing surfaces to support cell
      adhesion and spreading. In the present study, we have exploited the highly
      tailorable nature of these polymers to synthesize new versions possessing a wide
      range of chain lengths, with the intent of optimizing these materials for use as
      cell-supportive substrates. We find that longer nylon-3 chains lead to better
      fibroblast attachment on modified surfaces and that at the optimal chain lengths
      less hydrophobic subunits are superior. The best polymers we identified are
      comparable to an RGD-containing peptide in supporting fibroblast attachment. The
      results described here will help to focus future efforts aimed at refining nylon
      3 copolymer substrates for specific tissue engineering applications.

PMID- 22455339
TI  - Transgressive sexualities: politics of pleasure and desire in Kamasutra: a tale
      of love and fire.
AB  - Utilizing feminist film theory, critical reviews, and viewer responses, this
      article examines visual representations of transgressive sexuality in two
      diasporic Indian women's films: Kamasutra: A Tale of Love by Mira Nair, and Fire
      by Deepa Mehta. The article draws from research on ancient discourses on
      sexuality in India to argue that contemporary constructions of women's sexuality
      in South Asia are not devoid of patriarchal and fundamentalist cultural politics
      of representation.

PMID- 22455340
TI  - Sexual minority women's gender identity and expression: challenges and supports.
AB  - Sexual minority women were divided into four groups to study their gender
      identities (butch and femme), and gender expression (traditionally gendered and
      non-traditionally gendered women who do not identify as butch or femme).
      Experiences of heterosexist events (discrimination, harassment, threats of
      violence, victimization, negative emotions associated with these events), mental
      health (self esteem, stress, depression), and supports for a sexual minority
      identity (social support, outness, internalized homophobia) were examined across
      these groups. Findings suggested that butch-identified women experienced more
      heterosexist events than femme women or women with non-traditional gender
      expressions. There were no differences in mental health variables.

PMID- 22455341
TI  - The body that does not diminish itself: fat acceptance in Israel's lesbian queer
      communities.
AB  - This article follows Charlotte Cooper's call to widen fat studies scholarship to
      contexts outside the United States, and Adrianne Hill's call to locate
      historically specific connections between lesbian communities and promotion of
      fat acceptance. Three in-depth interviews were conducted with Jewish-Israeli fat
      women. Through the development of their ability to appreciate their fat body and
      the fat bodies of other women, participants employed a mixture of disparate
      feminist-lesbian and queer discourses, in a similar, albeit not identical manner
      to the one used in the U.S. context. One of the major differences is that
      queer/lesbian communities in Israel are not in contact with the Israeli fat
      acceptance movement.

PMID- 22455342
TI  - Under what conditions do lesbians disclose their sexual orientation to primary
      healthcare providers? A review of the literature.
AB  - Under what conditions do lesbians disclose their sexual orientation to primary
      healthcare providers? A review of the literature was undertaken to answer this
      question and to provide insight into the ways healthcare professionals can play
      an active role assisting their lesbian patients in "coming out." Thirty empirical
      studies met the inclusion criteria and were reviewed. Collectively, these
      separate studies have found that a myriad of internal (patient attributes) and
      external (healthcare context, patient-provider relationship) factors influence
      disclosure. The discussion highlights the critical role of healthcare
      professionals in supporting disclosure.

PMID- 22455343
TI  - Sarah was a butch: sexual identity, gender practices, and Sarah's place as mother
      in the Jewish National Pantheon.
AB  - Three fields of discourse regarding a masculine-like woman connect at a point
      that the queer field calls intersex, medical practice calls a sexual disorder,
      and rabbinic literature terms aylonit. The queer discursive field focuses on the
      freedom to choose an identity, but not the freedom from choosing one. The medical
      field focuses on sexual practice as the source of determining "normal" sexuality.
      In the discursive field of Jewish law there are no demands, because the Halakhic
      authority determines gender identity on behalf of the individual, maintaining
      ambiguity.

PMID- 22455344
TI  - Schulman's urban lesbian: a hobosexual pedestrian rhetoric.
AB  - The following article reads the protagonist in Sarah Schulman's Girls, Visions
      and Everything as not only lesbian, but as hobosexual-a concept representative of
      anti-capitalist practices in both sex and labor. The hobosexual is developed as
      an extension of the lesbian flaneur, as a concept that requires reading
      Schulman's urban lesbian at the intersection of class and sexuality. Lila
      Futuransky's sexual identity is suspended and complicated through an emphasis on
      her desire for queer mobility; her urban movements connect her to hobo history,
      but also expose the effects of capitalism that thwart her urban movement.

PMID- 22455346
TI  - Light on! Real world evaluation of a P300-based brain-computer interface (BCI)
      for environment control in a smart home.
AB  - Brain-computer interface (BCI) systems aim to enable interaction with other
      people and the environment without muscular activation by the exploitation of
      changes in brain signals due to the execution of cognitive tasks. In this
      context, the visual P300 potential appears suited to control smart homes through
      BCI spellers. The aim of this work is to evaluate whether the widely used
      character-speller is more sustainable than an icon-based one, designed to operate
      smart home environment or to communicate moods and needs. Nine subjects with
      neurodegenerative diseases and no BCI experience used both speller types in a
      real smart home environment. User experience during BCI tasks was evaluated
      recording concurrent physiological signals. Usability was assessed for each
      speller type immediately after use. Classification accuracy was lower for the
      icon-speller, which was also more attention demanding. However, in subjective
      evaluations, the effect of a real feedback partially counterbalanced the
      difficulty in BCI use. PRACTITIONER SUMMARY: Since inclusive BCIs require to
      consider interface sustainability, we evaluated different ergonomic aspects of
      the interaction of disabled users with a character-speller (goal: word spelling)
      and an icon-speller (goal: operating a real smart home). We found the first one
      as more sustainable in terms of accuracy and cognitive effort.

PMID- 22455347
TI  - Fluorescence anisotropy reduction of allosteric aptamer for sensitive and
      specific protein signaling.
AB  - Real time protein signaling in a complex medium may provide a promising way for
      high-throughput protein analysis, but it is largely unmet due to the challenge of
      signal transduction and the interferences of nonspecific binding and high
      background. Our recent work indicates that a fluorescent aptamer can display a
      protein binding-induced reduction of fluorescence anisotropy (FA) (Zhang, D.; Lu,
      M.; Wang, H. J. Am. Chem. Soc. 2011, 133, 9188-9191), which is exclusively
      different from a traditionally simplified concept hinting a molecular size
      increase-induced FA increase. Inspired by this unexpected observation, we
      describe a novel FA reduction approach for protein signaling. The feasibility of
      this approach is demonstrated through the assays of a blood protein human alpha
      thrombin and an oncoprotein human platelet-derived growth factor B-chain (PDGF
      BB) using two screened fluorescent aptamers, respectively. By the developed FA
      reduction method, the spiked human alpha-thrombin in diluted serum can be
      detected at the concentration as low as 250 pM. In contrast, in a traditional
      molecular size-dependent FA assay, the thrombin spiked in diluted serum cannot
      induce reliable FA change even at a 256-fold higher concentration (64 nM). The
      results clearly show that the FA reduction approach has a dramatically enhanced
      specificity against target protein and high sensitivity in complex medium and is
      applicable to the no-separation based detection of proteins in biological
      matrixes.

PMID- 22455349
TI  - Combined factors influencing the aggregation and deposition of nano-TiO2 in the
      presence of humic acid and bacteria.
AB  - This study investigates the contributions of natural organic matter (NOM) and
      bacteria to the aggregation and deposition of TiO(2) nanoparticles (TNPs) in
      aquatic environments. Transport experiments with TNPs were conducted in a
      microscopic parallel plate system and a macroscopic packed-bed column using
      fluorescently tagged E. coli as a model organism and Suwannee River Humic Acid as
      a representative NOM. Notably, TNPs were labeled with fluorescein isothiocyanate
      allowing particles and cells to be simultaneously visualized with a fluorescent
      microscope. Results from both experimental systems revealed that interactions
      among TNPs, NOM, and bacteria exhibited a significant dependence on solution
      chemistry (pH 5 and 7) and ion valence (K(+) and Ca(2+)), and that these
      interactions subsequently affect TNPs deposition. NOM and E. coli significantly
      reduced deposition of TNPs, with NOM having a greater stabilizing influence than
      bacteria. Ca(2+) ions played a significant role in these interactions, promoting
      formation of large clusters of TNPs, NOM, and bacteria. TNPs transport in the
      presence of both NOM and E. coli resulted in much less deposition than in the
      presence of NOM or E. coli alone, indicating a complex combination of
      interactions involved in stabilization. Generally, over the aquatic conditions
      considered, the extent of TNPs deposition follows: without NOM or bacteria > with
      bacteria only > with NOM only > combined bacteria and NOM. This trend should
      allow better prediction of the fate of TNPs in complex aquatic systems.

PMID- 22455351
TI  - Free radical biology of the cardiovascular system.
AB  - Most cardiovascular diseases (CVDs), as well as age-related cardiovascular
      alterations, are accompanied by increases in oxidative stress, usually due to
      increased generation and/or decreased metabolism of ROS (reactive oxygen species;
      for example superoxide radicals) and RNS (reactive nitrogen species; for example
      peroxynitrite). The superoxide anion is generated by several enzymatic reactions,
      including a variety of NADPH oxidases and uncoupled eNOS (endothelial NO
      synthase). To relieve the burden caused by this generation of free radicals,
      which also occurs as part of normal physiological processes, such as
      mitochondrial respiratory chain activity, mammalian systems have developed
      endogenous antioxidant enzymes. There is an increased usage of exogenous
      antioxidants such as vitamins C and E by many patients and the general public,
      ostensibly in an attempt to supplement intrinsic antioxidant activity.
      Unfortunately, the results of large-scale trails do not generate much enthusiasm
      for the continued use of antioxidants to mitigate free-radical-induced changes in
      the cardiovascular system. In the present paper, we review the clinical use of
      antioxidants by providing the rationale for their use and describe the outcomes
      of several large-scale trails that largely display negative outcomes. We also
      describe the emerging understanding of the detailed regulation of superoxide
      generation by an uncoupled eNOS and efforts to reverse eNOS uncoupling. SIRT1
      (sirtuin 1), which regulates the expression and activity of multiple pro- and
      anti-oxidant enzymes, could be considered a candidate molecule for a 'molecular
      switch'.

PMID- 22455353
TI  - Enzymatic immuno-assembly of gold nanoparticles for visualized activity screening
      of histone-modifying enzymes.
AB  - Activity screening of histone-modifying enzymes is of paramount importance for
      epigenetic research as well as clinical diagnostics and therapeutics. A novel
      biosensing strategy has been developed for sensitive and selective detection of
      histone-modifying enzymes as well as their inhibitors. This strategy relies on
      the antibody-mediated assembly of gold nanoparticles (AuNPs) decorated with
      substrate peptides that are subjected to enzymatic modifications by the histone
      modifying enzymes. This design allows a visual and homogeneous assay of the
      enzyme activity using antibodies without any labels, which circumvents the
      requirements to prefunctionalize the antibody and affords improved assay
      simplicity and throughput. Additionally, the use of antibody-based recognition of
      modified peptides could offer improved specificity as compared with existing
      techniques based on the enzyme coupled assay. We have demonstrated this strategy
      using a histone methyltransferase acting on histone H3 (Lys 4) and a histone
      acetyltransferase acting on histone H3 (Lys 14). The results reveal that the
      absorption peak characteristic for AuNPs decreases dynamically with increasing
      activity of the enzymes with concomitant visualizable color attenuation, and
      subnanomolar detection limits are readily achieved for both enzymes. The
      developed strategy can thus offer a robust and convenient visualized platform for
      screening the enzyme activities and their inhibitors with high sensitivity and
      selectivity.

PMID- 22455352
TI  - Ubiquitin-proteasome system inhibitors and AMPK regulation in hepatic cold
      ischaemia and reperfusion injury: possible mechanisms.
AB  - In the present Hypothesis article, we summarize and present data from the
      literature that support our hypothesis on the potential mechanisms by which UPS
      (ubiquitin-proteasome system) inhibitors reduce I/R (ischaemia/reperfusion)
      injury in the liver. I/R is the main cause of primary liver failure and,
      consequently, minimizing the detrimental effects of this process could increase
      the number of suitable transplantation grafts and also enhance the survival rate
      of patients after liver transplantation. A potential strategy to reduce I/R
      injury is the use of UPS inhibitors either as additives to preservation solutions
      or as drugs administered to patients. However, there is still controversy over
      whether the use of UPS inhibitors is beneficial or deleterious with regard to
      liver injury. From our experience and the few studies that have investigated the
      role of UPS in hepatic I/R, we believe that the use of UPS inhibitors is a
      potential strategy to reduce I/R injury in liver transplantation and graft
      preservation. We hypothesize that one of the main mechanisms of action of UPS
      inhibitors may be the up-regulation of AMPK (AMP-activated protein kinase)
      activity and the consequent down-regulation of mTOR (mammalian target of
      rapamycin), which may finally influence autophagy and preserve the energy state
      of the cell.

PMID- 22455350
TI  - Pre-eclampsia and offspring cardiovascular health: mechanistic insights from
      experimental studies.
AB  - Pre-eclampsia is increasingly recognized as more than an isolated disease of
      pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4
      fold increased risk of later cardiovascular disease. Intriguingly, the offspring
      of affected pregnancies also have an increased risk of higher blood pressure and
      almost double the risk of stroke in later life. Experimental approaches to
      identify the key features of pre-eclampsia responsible for this programming of
      offspring cardiovascular health, or the key biological pathways modified in the
      offspring, have the potential to highlight novel targets for early primary
      prevention strategies. As pre-eclampsia occurs in 2-5% of all pregnancies, the
      findings are relevant to the current healthcare of up to 3 million people in the
      U.K. and 15 million people in the U.S.A. In the present paper, we review the
      current literature that concerns potential mechanisms for adverse cardiovascular
      programming in offspring exposed to pre-eclampsia, considering two major areas of
      investigation: first, experimental models that mimic features of the in utero
      environment characteristic of pre-eclampsia, and secondly, how, in humans,
      offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We
      compare and contrast the findings from these two bodies of work to develop
      insights into the likely key pathways of relevance. The present review and
      analysis highlights the pivotal role of long-term changes in vascular function
      and identifies areas of growing interest, specifically, response to hypoxia,
      immune modification, epigenetics and the anti-angiogenic in utero milieu.

PMID- 22455354
TI  - Levamisole in cocaine: unexpected news from an old acquaintance.
AB  - Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties
      that was previously used in both animals and humans to treat inflammatory
      conditions and cancer. Levamisole has been identified as a cocaine adulterant in
      the United States since 2003. By 2009, the United States Drug Enforcement
      Administration (DEA) estimated that 69% of the cocaine seized contained
      levamisole. The first case reports of complications related to levamisole in
      cocaine users were published in 2009. The objectives of this article are to
      review the literature regarding the full spectrum of possible complications
      related to levamisole use for medical purposes, to review the current scope of
      levamisole-induced complications in cocaine users and to discuss the
      pharmacological properties that might explain the motivation behind the large
      scale adulteration of cocaine with levamisole. Literature review revealed that
      significant complications were quickly reported when levamisole was used in
      inflammatory conditions. By 1976, several cases of leukopenia and agranulocytosis
      were reported. Recurrence with re-exposure was well described and agranulocytosis
      spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to
      levamisole treatment was first reported in 1978 and mostly manifests as
      leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic
      vasculopathy without vasculitis. These findings typically, but not invariably,
      involve the ear lobes. Discontinuation of levamisole therapy was again a critical
      part of the treatment. Various neurological side effects were described with
      levamisole therapy, the most concerning complication being multifocal
      inflammatory leukoencephalopathy (MIL). Literature review identified 203 unique
      cases of complications in cocaine users that can be attributed to levamisole
      adulteration. The two principal complications reported are haematological (140
      cases of neutropenia) and dermatological (84 cases). Even though these
      complications can occur in isolation, many cases displayed both simultaneously.
      No formal case of leukoencephalopathy in the setting of cocaine use has been
      reported so far. A striking phenomenon is the apparent high level of recurrence
      (27.1%) of symptoms in cocaine users after re-exposure to cocaine that is
      presumably adulterated. The importance of accurately identifying levamisole
      induced complications is therefore critical for symptomatic patients as
      discontinuation of exposure is fundamental and as a correct diagnosis prevents
      unnecessary and potentially dangerous use of other treatment modalities like
      powerful immunosuppressive therapy. Literature review suggests that levamisole
      might have the advantages of enhancing noradrenergic neurotransmission by
      inhibiting reuptake, by inhibiting MAO and/or COMT, by acting on ganglionic
      nicotinic receptors and by being partially metabolized into an amphetamine-like
      compound. It could also increase endogenous opioids and increase dopamine
      concentration in the cerebral reward pathway. These potential effects make
      levamisole an interesting choice as a cocaine adulterant. It seems unlikely that
      levamisole use as a cocaine adulterant will soon reach an end. More information
      is needed about the diagnosis and treatment of levamisole-induced complications,
      and the efforts of the medical and public health community is needed to face this
      challenging problem.

PMID- 22455355
TI  - The acute effects of ethanol and acetaldehyde on physiological responses after
      ethanol ingestion in young healthy men with different ALDH2 genotypes.
AB  - BACKGROUND: This study investigated the acute effects of ethanol and acetaldehyde
      on physiological responses in healthy men according to ALDH2 genotype by
      measuring them directly in human blood. METHODS: Twenty-four men, 12 with the
      ALDH2*1/*1 genotype and 12 with the ALDH2*1/*2 genotype, were selected. In a
      double-blind placebo-controlled crossover design, each subject was administered
      one of three doses of ethanol (0.25, 0.5 or 0.75 g/kg) or a placebo on four
      separate occasions. The blood ethanol concentration (BEC), blood acetaldehyde
      concentration (BAAC) and physiological responses including facial redness, pulse
      rate and systolic and diastolic blood pressures were assessed. RESULTS:
      Significant differences were observed in the physiological responses between the
      ALDH2*1/*2 and ALDH2*1/*1 groups. Significant gene effects were observed for
      pulse rate and facial flushing (F-values =62.344; p values <0.001 and F-values
      =7.062; p values =0.010, respectively, by repeated-measures analysis of
      variance), which were significantly greater in subjects with the ALDH2*1/*2
      genotype. In a linear regression analysis, BAAC significantly predicted increased
      facial redness at 30 minutes (adjusted R( 2 ): 0.209; p values <0.001) and pulse
      rate at 30, 60, 90 and 120 minutes (adjusted R( 2 ): 0.454, 0.490, 0.428 and
      0.193, respectively; all p values <0.001), whereas BEC was not associated with
      any physiological response measure at any time. CONCLUSIONS: Facial redness and
      pulse rate after ethanol ingestion were significantly higher in the ALDH2*1/*2
      genotype, and were significantly associated with blood acetaldehyde
      concentrations. The acute effects of ethanol on the physiological responses were
      mediated mainly by acetaldehyde, the active metabolite of ethanol, rather than by
      ethanol itself.

PMID- 22455356
TI  - Electrophysiological correlates of respiratory failure in acute organophosphate
      poisoning: evidence for differential roles of muscarinic and nicotinic
      stimulation.
AB  - BACKGROUND: Respiratory failure in acute organophosphate (OP) poisoning can occur
      early and also relatively late in the clinical course, and the pathophysiology of
      respiratory failure at these different phases may have important clinical
      implications. Objective. To compare the electrophysiological findings in patients
      with early and late respiratory failure following acute OP poisoning. METHODS: A
      prospective observational case series of consenting symptomatic patients with
      acute OP poisoning were assessed with daily physical examinations and repetitive
      nerve stimulation (RNS) studies. RNS was done on right and left median and ulnar
      nerves at 1, 3, 10, 15, 20, and 30 Hz. Outcomes such as need for ventilation and
      development of intermediate syndrome (IMS) were noted. Early respiratory failure
      was defined as occurring within 24 hours of ingestion. RESULTS: Seventy-eight
      patients were recruited for the clinical and electrophysiological study and of
      those 59 (75.6%) patients had ingested chlorpyrifos. Seven patients developed
      respiratory failure within 24 hours of ingestion with overt muscarinic signs.
      They had no electrophysiological abnormalities at median and ulnar nerves before
      intubation. Three of them later developed "forme fruste" IMS. Five other patients
      developed late respiratory failure after 24 hours of ingestion, and all of them
      showed progressive RNS changes indicating severe IMS prior to intubation.
      CONCLUSION: The normal RNS in all patients developing early respiratory failure
      suggests that it is due to a central nervous system (CNS) and muscarinic effect.
      This emphasizes the need for early rapid atropinisation as a priority, combating
      the nicotinic effects being less urgent. This is in contrast with the late
      respiratory failure, which has been shown to be associated with neuromuscular
      dysfunction. Further studies are needed to quantify CNS and muscarinic
      dysfunction to assist in the development of better treatments for the severe and
      early OP poisoning.

PMID- 22455358
TI  - Severe cobalt intoxication following hip replacement revision: clinical features
      and outcome.
AB  - CONTEXT: Cobalt intoxication has become more frequent due to the wide use of
      metal hip implants. CASE DETAILS: A 56-year-old male patient underwent total hip
      prosthesis, with a ceramics-on-ceramics implant. Almost 3 years later, it was
      replaced by metal implant containing cobalt, chromium, and titanium. He developed
      weight loss, heart, thyroid, and neurological toxicity, with severe hearing loss.
      He was treated with 2,3-dimercaptopropane-1-sulfonate (DMPS), and cobalt
      excretion increased. Clinical symptoms apart from deafness gradually resolved.
      CONCLUSION: We report significant cobalt poisoning from a damaged hip replacement
      with cobalt containing implant and a slow abrasion of the metal by residual
      ceramic particles. Chelation therapy resulted in apparent benefit.

PMID- 22455357
TI  - Hospital mortality among poisoned patients presenting unconscious.
AB  - OBJECTIVES: The hospital mortality from acute poisoning in the western world is
      approximately 0.6%. However, this figure is based on series of consecutive cases,
      including mild intoxications. The aim of this paper was to investigate the
      mortality among poisoned patients with CNS depression on admission. DESIGN: This
      report is based on two case series. One observational study of 352 prospectively
      included cases of poisoning with a Glasgow coma scale (GCS) score <=10 at
      presentation during the 2-year-period 2003-2005, and one retrospective review of
      all poisonings admitted to a hospital in Stockholm 2009-2011. RESULTS: The
      observational study showed a hospital mortality rate of 2.8%. Nine of the 10
      fatalities had a GCS score below 7 on admission. The more recent retrospective
      review consisted of 1314 cases of poisoning of whom 419 (32%) had a GCS score
      <=10 on admission. The hospital mortality among these 419 cases was 2.4%. All 10
      deaths in this cohort had a GCS score below 7 at presentation. The subgroup of
      patients pooled from both case series with a GCS score of 3-6 (n =444) had a
      mortality rate of 4.3%. CONCLUSIONS: Based on the findings in this report, and on
      a literature search, about 30% of hospitalized poisonings have a significant CNS
      depression on admission. Based on our experience, cases of poisoning with a GCS
      score of 7-10 on admission do not seem to have a worse prognosis than poisonings
      in general. However, cases of poisoning presenting with deeper coma (GCS score 3
      6) have a mortality rate approximately seven times higher than the overall
      hospital mortality from acute poisoning.

PMID- 22455359
TI  - Multiple lead appendoliths following ingestion of lead shot: time course and
      removal by laporoscopic appendectomy.
AB  - Systemic lead poisoning may occur from ingested lead foreign bodies. Rarely,
      these may cause a retained appendolith. The risks of lead toxicity from these
      appendoliths, the time course of retention in the appendix, the rapidity of
      inhibition of heme synthesis, and the best approach to removal remain
      controversial. Fourteen days post-ingestion of a "handful" of lead shot, a 15
      year-old male was admitted for elevated lead level; an x-ray showed aggregation
      of many pellets in the teen's appendix. A laparoscopic appendectomy was
      performed; examination of the removed appendix revealed greater than 50 retained
      pellets. An abdominal film obtained post-procedure showed removal of all but
      three of the pellets. Results from admission blood work found a blood lead level
      of 41 mcg/dL and free erythrocyte porphyrin (FEP) level of 114 MUmol/mol heme
      (reference normal <70). After a short recovery the patient was discharged on
      succimer chelation therapy and on follow up, his lead level was <5 mcg/dL.

PMID- 22455360
TI  - Hydrogen peroxide ingestions: the scope of the injury.

PMID- 22455364
TI  - Parvalbumin gene transfer impairs skeletal muscle contractility in old mice.
AB  - Sarcopenia is the progressive age-related loss of skeletal muscle mass associated
      with functional impairments that reduce mobility and quality of life. Overt
      muscle wasting with sarcopenia is usually preceded by a slowing of the rate of
      relaxation and a reduction in maximum force production. Parvalbumin (PV) is a
      cytosolic Ca(2+) buffer thought to facilitate relaxation in muscle. We tested the
      hypothesis that restoration of PV levels in muscles of old mice would increase
      the magnitude and hasten relaxation of submaximal and maximal force responses.
      The tibialis anterior (TA) muscles of young (6 month), adult (13 month), and old
      (26 month) C57BL/6 mice received electroporation-assisted gene transfer of
      plasmid encoding PV or empty plasmid (pcDNA3.1). Contractile properties of TA
      muscles were assessed in situ 14 days after transfer. In old mice, muscles with
      increased PV expression had a 40% slower rate of tetanic force development
      (p<0.01), and maximum twitch and tetanic force were 22% and 16% lower than
      control values, respectively (p<0.05). Muscles with increased PV expression from
      old mice had an 18% lower maximum specific (normalized) force than controls, and
      absolute force was '26% lower at higher stimulation frequencies (150-300 Hz,
      p<0.05). In contrast, there was no effect of increased PV expression on TA muscle
      contractile properties in young and adult mice. The impairments in skeletal
      muscle function in old mice argue against PV overexpression as a therapeutic
      strategy for ameliorating aspects of contractile dysfunction with sarcopenia and
      help clarify directions for therapeutic interventions for age-related changes in
      skeletal muscle structure and function.

PMID- 22455365
TI  - Secreted factors of human liver-derived mesenchymal stem cells promote liver
      regeneration early after partial hepatectomy.
AB  - Rapid liver regeneration is required after living-donor liver transplantation and
      oncologic liver resections to warrant sufficient liver function and prevent small
      for-size syndrome. Recent evidence highlights the therapeutic potential of
      mesenchymal stem cells (MSC) for treatment of toxic liver injury, but whether MSC
      and their secreted factors stimulate liver regeneration after surgical injury
      remains unknown. Therefore, the aim of this study is to investigate the effect of
      human liver-derived MSC-secreted factors in an experimental liver resection
      model. C57BL/6 mice were subjected to a 70% partial hepatectomy and treated with
      either concentrated MSC-conditioned culture medium (MSC-CM) or vehicle control.
      Animals were analyzed for liver and body weight, hepatocyte proliferation, and
      hepatic gene expression. Effects of MSC-CM on gene expression in a human
      hepatocyte-like cell line (Huh7 cells) were analyzed using genome-wide gene
      expression arrays. Liver regeneration was significantly stimulated by MSC-CM as
      shown by an increase in liver to body weight ratio and hepatocyte proliferation.
      MSC-CM upregulated hepatic gene expression of cytokines and growth factors
      relevant for cell proliferation, angiogenesis, and anti-inflammatory responses.
      In vitro, treatment of Huh7 cells with MSC-CM significantly altered expression
      levels of ~3,000 genes. Functional analysis revealed strong effects on networks
      associated with protein synthesis, cell survival, and cell proliferation. This
      study shows that treatment with MSC-derived factors can promote hepatocyte
      proliferation and regenerative responses in the early phase after surgical
      resection. MSC-CM may represent a feasible new strategy to promote liver
      regeneration in patients undergoing extensive liver resection or after
      transplantation of small liver grafts.

PMID- 22455366
TI  - Relationship between susceptibility of Blackface sheep to Teladorsagia
      circumcincta infection and an inflammatory mucosal T cell response.
AB  - Teladorsagia circumcincta is the most economically important gastrointestinal
      (abomasal) nematode parasite of sheep in cool temperate regions, to which sheep
      show genetically-varying resistance to infection. Lambs, from parents with
      genetic variation for resistance, were trickle infected with L3 larvae over 12
      weeks. 45 lambs were identified with a range of susceptibilities as assessed by:
      adult worm count at post mortem, faecal egg count (FEC) and IgA antibody levels.
      This project investigated the correlation of T cell cytokine expression and
      resistance to infection at the mature stage of response, when the resistant lambs
      had excluded all parasites.Histopathology showed only minor changes in resistant
      animals with a low level lymphocyte infiltration; but in susceptible lambs, major
      pathological changes were associated with extensive infiltration of lymphocytes,
      eosinophils and neutrophils.Absolute quantitative RT-qPCR assays on the abomasal
      lymph node (ALN) revealed a significant positive correlation between IL6, IL21
      and IL23A transcript levels with adult worm count and FEC. IL23A was also
      negatively correlated with IgA antibody levels. Significantly positive
      correlation of TGFB1 levels with adult worm count and FEC were also seen in the
      abomasal mucosa. These data are consistent with the hypothesis that the inability
      to control L3 larval colonization, adult worm infection and egg production is due
      to the activation of the inflammatory Th17 T cell subset.

PMID- 22455368
TI  - Isolable analogues of the Breslow intermediate derived from chiral triazolylidene
      carbenes.
AB  - Since Breslow's initial report on the thiamine mode of action, the study of
      catalytic acyl carbanion processes has been an area of immense interest. With the
      advent of azolylidene catalysis, a plethora of reactivtiy has been harnessed, but
      the crucial nucleophilic intermediate proposed by Breslow had never been isolated
      or fully characterized. Herein, we report the isolation and full characterization
      of nitrogen analogues of the Breslow intermediate. Both stable and catalytically
      relevant, these species provide a model system for the study of acyl carbanion
      and homoenolate processes catalyzed by triazolylidene carbenes.

PMID- 22455367
TI  - Artemisinin combination therapies price disparity between government and private
      health sectors and its implication on antimalarial drug consumption pattern in
      Morogoro Urban District, Tanzania.
AB  - BACKGROUND: Universal access to effective treatments is a goal of the Roll Back
      Malaria Partnership. However, despite official commitments and substantial
      increases in financing, this objective remains elusive, as development assistance
      continue to be routed largely through government channels, leaving the much
      needed highly effective treatments inaccessible or unaffordable to those seeking
      services in the private sector. METHODS: To quantify the effect of price
      disparity between the government and private health systems, this study have
      audited 92 government and private Drug Selling Units (DSUs) in Morogoro urban
      district in Tanzania to determine the levels, trend and consumption pattern of
      antimalarial drugs in the two health systems. A combination of observation,
      interviews and questionnaire administered to the service providers of the
      randomly selected DSUs were used to collect data. RESULTS: ALU was the most
      selling antimalarial drug in the government health system at a subsidized price
      of 300 TShs (0.18 US$). By contrast, ALU that was available in the private sector
      (coartem) was being sold at a price of about 10,000 TShs (5.9 US$), the price
      that was by far unaffordable, prompting people to resort to cheap but failed
      drugs. As a result, metakelfin (the phased out drug) was the most selling drug in
      the private health system at a price ranging from 500 to 2,000 TShs (0.29-1.18
      US$). CONCLUSIONS: In order for the prompt diagnosis and treatment with effective
      drugs intervention to have big impact on malaria in mostly low socioeconomic
      malaria-endemic areas of Africa, inequities in affordability and access to
      effective treatment must be eliminated. For this to be ensued, subsidized drugs
      should be made available in both government and private health sectors to promote
      a universal access to effective safe and affordable life saving antimalarial
      drugs.

PMID- 22455369
TI  - In-home solid fuel use and cardiovascular disease: a cross-sectional analysis of
      the Shanghai Putuo study.
AB  - BACKGROUND: Although recent research evidence suggests an association between
      household air pollution from solid fuel use, such as coal or biomass, and
      cardiovascular events such as hypertension, little epidemiologic data are
      available concerning such exposure effects on cardiovascular endpoints other than
      hypertension. We explored the association between in-home solid fuel use and self
      reported diagnoses of cardiovascular endpoints, such as hypertension, coronary
      heart disease (CHD), stroke, and diabetes. METHODS: We analyzed 14,068 Chinese
      adults, aged 18 years and older. Odds ratios (OR) and the corresponding 95%
      confidence intervals (CI) were estimated using logistic regression models for the
      risk of each outcome after adjusting for potential confounders. RESULTS: The use
      of solid fuel in home was significantly associated with an increased risk for
      hypertension (OR 1.70, 95% CI 1.40 to 2.07), CHD (OR 2.58, 95% CI 1.53 to 4.32),
      and diabetes (OR 2.48, 95% CI 1.59 to 3.86), after adjusting for potential
      confounders. Compared with individuals in the lowest tertile of the duration of
      solid fuel exposure, those in the highest tertile of the duration of solid fuel
      exposure had an increased odds of hypertension (OR 1.73, 95% CI 1.45 to 2.06),
      stroke (OR 1.87, 95% CI 1.03 to 3.38), and diabetes (OR 3.18, 95% CI 2.11 to
      4.78). CONCLUSIONS: Our data suggest that in-home solid fuel exposure maybe
      associated with increased risk for hypertension, CHD, stroke, and diabetes in the
      Chinese adult population. Further large-scale longitudinal studies are warranted
      to confirm these findings.

PMID- 22455371
TI  - Clinical stage of Merkel cell carcinoma and survival are not associated with
      Breslow thickness of biopsied tumor.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignancy that often
      presents on the skin with concurrent metastatic disease. OBJECTIVE: To determine
      whether Breslow thickness of biopsied MCC correlates with clinical disease stage.
      MATERIALS AND METHODS: We performed a retrospective review of clinical data and
      histopathology specimens from 34 individuals with MCC treated at the Roswell Park
      Cancer Institute for whom complete clinical information and histopathology
      specimens were available. RESULTS: There was no correlation between Breslow
      thickness of biopsied MCC on the head and neck or body and clinical stage of
      disease, progression-free survival, or overall survival. Hence, thin MCCs should
      not be taken to represent lesions with less-aggressive clinical behavior.
      CONCLUSION: Our findings validate the current practice of staging all newly
      diagnosed MCC, irrespective of size or Breslow thickness.

PMID- 22455370
TI  - Breast cancer stage at diagnosis and area-based socioeconomic status: a
      multicenter 10-year retrospective clinical epidemiological study in China.
AB  - BACKGROUND: Although socioeconomic status (SES) has been focused on as a key
      determinant of cancer stage at diagosis in western countries, there has been no
      systemic study on the relationship of SES and breast cancer stage at diagnosis in
      China. METHODS: The medical charts of 4,211 eligible breast cancer patients from
      7 areas across China who were diagnosed between 1999 and 2008 were reviewed. Four
      area-based socioeconomic indicators were used to calculate area-based SES by
      cluster analysis. The associations between area-based SES and stage at diagnosis
      were analyzed by trend chi-square tests. Binary logistic regression was performed
      to estimate odds ratios for individual demographic characteristics' effects on
      cancer stages, stratified by area-based SES. RESULTS: The individual demographic
      and pathologic characteristics of breast cancer cases were significantly
      different among the seven areas studied. More breast cancer cases in low SES
      areas (25.5%) were diagnosed later (stages III & IV) than those in high (20.4%)
      or highest (14.8%) SES areas (chi2 for trend = 80.79, P < 0.001). When area-based
      SES is controlled for, in high SES areas, cases with less education were more
      likely to be diagnosed at later stages compared with more educated cases. In low
      SES areas, working women appeared to be diagnosed at earlier breast cancer stages
      than were homemakers (OR: 0.18-0.26). CONCLUSIONS: In China, women in low SES
      areas are more likely to be diagnosed at later breast cancer stages than those in
      high SES areas.

PMID- 22455372
TI  - A covert attention P300-based brain-computer interface: Geospell.
AB  - The Farwell and Donchin P300 speller interface is one of the most widely used
      brain-computer interface (BCI) paradigms for writing text. Recent studies have
      shown that the recognition accuracy of the P300 speller decreases significantly
      when eye movement is impaired. This report introduces the GeoSpell interface
      (Geometric Speller), which implements a stimulation framework for a P300-based
      BCI that has been optimised for operation in covert visual attention. We compared
      the Geospell with the P300 speller interface under overt attention conditions
      with regard to effectiveness, efficiency and user satisfaction. Ten healthy
      subjects participated in the study. The performance of the GeoSpell interface in
      covert attention was comparable with that of the P300 speller in overt attention.
      As expected, the effectiveness of the spelling decreased with the new interface
      in covert attention. The NASA task load index (TLX) for workload assessment did
      not differ significantly between the two modalities. PRACTITIONER SUMMARY: This
      study introduces and evaluates a gaze-independent, P300-based brain-computer
      interface, the efficacy and user satisfaction of which were comparable with those
      off the classical P300 speller. Despite a decrease in effectiveness due to the
      use of covert attention, the performance of the GeoSpell far exceeded the
      threshold of accuracy with regard to effective spelling.

PMID- 22455373
TI  - Critical evaluation of the 2D-CSIA scheme for distinguishing fuel oxygenate
      degradation reaction mechanisms.
AB  - Although the uniform initial hydroxylation of methyl tert-butyl ether (MTBE) and
      other oxygenates during aerobic biodegradation has already been proven by
      molecular tools, variations in carbon and hydrogen enrichment factors (epsilon(C)
      and epsilon(H)) have still been associated with different reaction mechanisms
      (McKelvie et al. Environ. Sci. Technol. 2009, 43, 2793-2799). Here, we present
      new laboratory-derived epsilon(C) and epsilon(H) data on the initial degradation
      mechanisms of MTBE, ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether
      (TAME) by chemical oxidation (permanganate, Fenton reagents), acid hydrolysis,
      and aerobic bacteria cultures (species of Aquincola, Methylibium, Gordonia,
      Mycobacterium, Pseudomonas, and Rhodococcus). Plotting of Deltadelta(2)H/
      Deltadelta(13)C data from chemical oxidation and hydrolysis of ethers resulted in
      slopes (Lambda values) of 22 +/- 4 and between 6 and 12, respectively. With A.
      tertiaricarbonis L108, R. zopfii IFP 2005, and Gordonia sp. IFP 2009, epsilon(C)
      was low (<|-1|0/00) and epsilon(H) was insignificant. Fractionation obtained with
      P. putida GPo1 was similar to acid hydrolysis and M. austroafricanum JOB5 and R.
      ruber DSM 7511 displayed Lambda values previously only ascribed to anaerobic
      attack. The fractionation patterns rather correlate with the employment of
      different P450, AlkB, and other monooxygenases, likely catalyzing ether
      hydroxylation via different transition states. Our data questions the value of 2D
      CSIA for a simple distinguishing of oxygenate biotransformation mechanisms,
      therefore caution and complementary tools are needed for proper interpretation of
      groundwater plumes at field sites.

PMID- 22455374
TI  - Effects of a single water molecule on the OH + H2O2 reaction.
AB  - The effect of a single water molecule on the reaction between H(2)O(2) and HO has
      been investigated by employing MP2 and CCSD(T) theoretical approaches in
      connection with the aug-cc-PVDZ, aug-cc-PVTZ, and aug-cc-PVQZ basis sets and
      extrapolation to an infinity basis set. The reaction without water has two
      elementary reaction paths that differ from each other in the orientation of the
      hydrogen atom of the hydroxyl radical moiety. Our computed rate constant, at 298
      K, is 1.56 * 10(-12) cm(3) molecule(-1) s(-1), in excellent agreement with the
      suggested value by the NASA/JPL evaluation. The influence of water vapor has been
      investigated by considering either that H(2)O(2) first forms a complex with water
      that reacts with hydroxyl radical or that H(2)O(2) reacts with a previously
      formed H(2)O.OH complex. With the addition of water, the reaction mechanism
      becomes much more complex, yielding four different reaction paths. Two pathways
      do not undergo the oxidation reaction but an exchange reaction where there is an
      interchange between H(2)O(2).H(2)O and H(2)O.OH complexes. The other two pathways
      oxidize H(2)O(2), with a computed total rate constant of 4.09 * 10(-12) cm(3)
      molecule(-1) s(-1) at 298 K, 2.6 times the value of the rate constant of the
      unassisted reaction. However, the true effect of water vapor requires taking into
      account the concentration of the prereactive bimolecular complex, namely,
      H(2)O(2).H(2)O. With this consideration, water can actually slow down the
      oxidation of H(2)O(2) by OH between 1840 and 20.5 times in the 240-425 K
      temperature range. This is an example that demonstrates how water could be a
      catalyst in an atmospheric reaction in the laboratory but is slow under
      atmospheric conditions.

PMID- 22455375
TI  - Bayesian approach to the analysis of fluorescence correlation spectroscopy data
      II: application to simulated and in vitro data.
AB  - Fluorescence correlation spectroscopy (FCS) is a powerful approach to
      characterizing the binding and transport dynamics of macromolecules. The unbiased
      interpretation of FCS data relies on the evaluation of multiple competing
      hypotheses to describe an underlying physical process under study, which is
      typically unknown a priori. Bayesian inference provides a convenient framework
      for this evaluation based on the temporal autocorrelation function (TACF), as
      previously shown theoretically using model TACF curves (He, J., Guo, S., and
      Bathe, M. Anal. Chem. 2012, 84). Here, we apply this procedure to simulated and
      experimentally measured photon-count traces analyzed using a multitau correlator,
      which results in complex noise properties in TACF curves that cannot be modeled
      easily. As a critical component of our technique, we develop two means of
      estimating the noise in TACF curves based either on multiple independent TACF
      curves themselves or a single raw underlying intensity trace, including a general
      procedure to ensure that independent, uncorrelated samples are used in the latter
      approach. Using these noise definitions, we demonstrate that the Bayesian
      approach selects the simplest hypothesis that describes the FCS data based on
      sampling and signal limitations, naturally avoiding overfitting. Further, we show
      that model probabilities computed using the Bayesian approach provide a
      reliability test for the downstream interpretation of model parameter values
      estimated from FCS data. Our procedure is generally applicable to FCS and image
      correlation spectroscopy and therefore provides an important advance in the
      application of these methods to the quantitative biophysical investigation of
      complex analytical and biological systems.

PMID- 22455376
TI  - Genetically encoded photo-cross-linkers map the binding site of an allosteric
      drug on a G protein-coupled receptor.
AB  - G protein-coupled receptors (GPCRs) are dynamic membrane proteins that bind
      extracellular molecules to transduce signals. Although GPCRs represent the
      largest class of therapeutic targets, only a small percentage of their ligand
      binding sites are precisely defined. Here we describe the novel application of
      targeted photo-cross-linking using unnatural amino acids to obtain structural
      information about the allosteric binding site of a small molecule drug, the CCR5
      targeted HIV-1 co-receptor blocker maraviroc.

PMID- 22455377
TI  - Characterization of various deformable liposomes with metronidazole.
AB  - OBJECTIVE: The aim of this study was to investigate various deformable liposomes
      for their potential application for the vaginal administration of metronidazole.
      MATERIALS AND METHODS: Deformable liposomes composed of egg phosphatidylcholine
      (EPC) and various surfactants [sodium deoxycholate (SDCh), Tween 80 or Span 80]
      and conventional liposomes consisting of EPC and egg phosphatidylglycerol-sodium
      (EPG-Na) were prepared with and without metronidazole. Additionally, a freeze
      thaw method was applied to both classes of vesicles (liposomes) containing the
      drug to improve its trapping capacity. All of the liposomes prepared were
      characterized and compared in terms of size, polydispersity, zeta potential,
      entrapment efficiency and their permeability on a Caco-2 cell monolayer. RESULTS
      AND DISCUSSION: Conventional liposomes, both with and without metronidazole, were
      larger than the deformable vesicles. The presence of ethanol in the preparations
      of the elastic EPC/SDCh and EPC/Tween 80 liposomes was found to affect the
      particle size in terms of reducing this parameter. Different types of vesicles
      were compared for their trapping efficiency of metronidazole and the highest
      entrapment was observed with conventional liposomes. However, deformable EPC/SDCh
      liposomes were found to enhance the permeability of metronidazole more
      effectively than the conventional liposomes based on the in vitro model of the
      epithelial barrier. CONCLUSION: These preliminary data indicate that EPC/SDCh
      liposomes may have a promising future in vaginal delivery of metronidazole.
      Therefore, additional investigations on elastic vesicles and their incorporation
      in a suitable vehicle should be considered to further evaluate their
      applicability in vaginal drug delivery.

PMID- 22455379
TI  - Analyses that inform policy decisions.

PMID- 22455378
TI  - Tailored integrin-extracellular matrix interactions to direct human mesenchymal
      stem cell differentiation.
AB  - Integrins provide the primary link between mesenchymal stem cells (MSCs) and
      their surrounding extracellular matrix (ECM), with different integrin pairs
      having specificity for different ECM molecules or peptide sequences contained
      within them. It is widely acknowledged that the type of ECM present can influence
      MSC differentiation; however, it is yet to be determined how specific integrin
      ECM interactions may alter this or how they change during differentiation. We
      determined that human bone marrow-derived mesenchymal stem cells (hMSCs) express
      a broad range of integrins in their undifferentiated state and show a dramatic,
      but transient, increase in the level of alpha5 integrin on day 7 of osteogenesis
      and an increase in alpha6 integrin expression throughout adipogenesis. We used a
      nonfouling polystyrene-block-poly(ethylene oxide)-copolymer (PS-PEO) surface to
      present short peptides with defined integrin-binding capabilities (RGD, IKVAV,
      YIGSR, and RETTAWA) to hMSCs and investigate the effects of such specific
      integrin-ECM contacts on differentiation. hMSCs cultured on these peptides
      displayed different morphologies and had varying abilities to differentiate along
      the osteogenic and adipogenic lineages. The peptide sequences most conducive to
      differentiation (IKVAV for osteogenesis and RETTAWA and IKVAV for adipogenesis)
      were not necessarily those that were bound by those integrin subunits seen to
      increase during differentiation. Additionally, we also determined that
      presentation of RGD, which is bound by multiple integrins, was required to
      support long-term viability of hMSCs. Overall we confirm that integrin-ECM
      contacts change throughout hMSC differentiation and show that surfaces presenting
      defined peptide sequences can be used to target specific integrins and ultimately
      influence hMSC differentiation. This platform also provides information for the
      development of biomaterials capable of directing hMSC differentiation for use in
      tissue engineering therapies.

PMID- 22455380
TI  - Degradable conjugates from oxanorbornadiene reagents.
AB  - Oxanorbornadienedicarboxylate (OND) reagents were explored for purposes of
      binding and releasing drugs from serum albumins as representative macromolecular
      carriers. Being highly reactive Michael acceptors, ONDs form adducts with thiols
      and amines, which then undergo retro-Diels-Alder fragmentation. A study of more
      than 30 model adducts revealed a number of modifications that can be used to
      influence adduct stability. For the most reactive OND linkers, the labeling of
      the single available bovine serum albumin (BSA) cysteine residue was complete
      within minutes at a mid-micromolar concentration of reactants. While a
      selectivity of greater than 1000-fold for thiol over amine was observed with
      model amino acids, the labeling of protein amines with ONDs is fast enough to be
      practical, as demonstrated by the reaction with thiol-depleted BSA. The OND-amine
      adducts were found to be up to 15 times more stable than OND-thiol adducts, and
      to be sensitive to acid by virtue of a stereochemically dependent acceleration of
      cycloreversion. The release rate of fluorescent cargo from serum albumins was
      tuned by selecting the coupling partners: the available half-lives ranged from 40
      min to 7 days at 37  degrees C. Such versatility of release profiles from protein
      carriers, controlled by the nature of the OND linkage, is a useful addition to
      the drug delivery toolbox.

PMID- 22455381
TI  - A shared-care model of obesity treatment for 3-10 year old children: protocol for
      the HopSCOTCH randomised controlled trial.
AB  - BACKGROUND: Despite record rates of childhood obesity, effective evidence-based
      treatments remain elusive. While prolonged tertiary specialist clinical input has
      some individual impact, these services are only available to very few children.
      Effective treatments that are easily accessible for all overweight and obese
      children in the community are urgently required. General practitioners are
      logical care providers for obese children but high-quality trials indicate that,
      even with substantial training and support, general practitioner care alone will
      not suffice to improve body mass index (BMI) trajectories. HopSCOTCH (the Shared
      Care Obesity Trial in Children) will determine whether a shared-care model, in
      which paediatric obesity specialists co-manage obesity with general
      practitioners, can improve adiposity in obese children. DESIGN: Randomised
      controlled trial nested within a cross-sectional BMI survey conducted across 22
      general practices in Melbourne, Australia. PARTICIPANTS: Children aged 3-10 years
      identified as obese by Centers for Disease Control criteria at their family
      practice, and randomised to either a shared-care intervention or usual care.
      INTERVENTION: A single multidisciplinary obesity clinic appointment at
      Melbourne's Royal Children's Hospital, followed by regular appointments with the
      child's general practitioner over a 12 month period. To support both specialist
      and general practice consultations, web-based shared-care software was developed
      to record assessment, set goals and actions, provide information to caregivers,
      facilitate communication between the two professional groups, and jointly track
      progress. OUTCOMES: Primary - change in BMI z-score. Secondary - change in
      percentage fat and waist circumference; health status, body satisfaction and
      global self-worth. DISCUSSION: This will be the first efficacy trial of a general
      practitioner based, shared-care model of childhood obesity management. If
      effective, it could greatly improve access to care for obese children. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12608000055303.

PMID- 22455382
TI  - Androgen receptor-beta mRNA levels in different tissues in breeding and post
      breeding male and female sticklebacks, Gasterosteus aculeatus.
AB  - BACKGROUND: Androgens induce male characters by activating androgen receptors
      (AR). Previous quantitative studies on AR in fishes have been limited to few
      tissues and/or a single season/reproductive state. The aim of this investigation
      was to study the possible role of AR-beta expression levels in the control of
      male traits in the three-spined stickleback. To that end, AR-beta expression
      levels in major tissues in breeding and post-breeding male and female
      sticklebacks were examined. METHODS: AR-beta mRNA levels were quantified in ten
      tissues; eye, liver, axial muscle, heart, brain, intestine, ovary, testis, kidney
      and pectoral muscle in six breeding and post-breeding males and females using
      reverse transcription quantitative PCR. RESULTS: Breeding in contrast to post
      breeding males built nests and showed secondary sexual characters (e.g. kidney
      hypertrophy) and elevated androgen levels. Post-breeding females had lower
      ovarian weights and testosterone levels than breeding females. AR-beta was
      expressed in all studied tissues in both sexes and reproductive states with the
      highest expression in the gonads and in the kidneys. The kidney is an androgen
      target organ in sticklebacks, from which breeding males produce the protein
      spiggin, which is used in nest-building. There was also high AR-beta expression
      in the intestine, an organ that appears to take over hyperosmo-regulation in
      fresh water when the kidney hypertrophies in mature males and largely loses this
      function. The only tissue that showed effects of sex or reproductive state on AR
      beta mRNA levels was the kidneys, where post-breeding males displayed higher AR
      beta mRNA levels than breeding males. CONCLUSION: The results indicate that
      changes in AR-beta mRNA levels play no or little role in changes in androgen
      dependent traits in the male stickleback.

PMID- 22455383
TI  - Computational design and discovery of "minimally structured" hERG blockers.
AB  - Molecular knowledge of hERG blocking liability can offer the possibility of
      optimizing lead compounds in a way that eliminates potentially lethal side
      effects. In this study, we computationally designed, synthesized, and tested a
      small series of "minimally structured" molecules. Some of these compounds were
      remarkably potent against hERG (6, IC(50) = 2.4 nM), allowing us to identify the
      minimal structural requirements for hERG blocking liability.

PMID- 22455384
TI  - Impacts of wheelchair acquisition on children from a person-occupation
      environment interactional perspective.
AB  - PURPOSE: Mobility aids not only compensate for a locomotor disability, they also
      increase users' opportunities for social participation. The objective was to
      explore the impacts of wheelchair (WC) acquisition on children's social
      participation, personal factors and social environment. METHODS: A literature
      review was done in MEDLINE for the years 1996 to 2011 (June) with an age range
      from birth to 12 years. The studies selected had to be in French or English and
      concern the impacts of a WC on children, their social participation or social
      environment. RESULTS: The studies retained (n = 9) indicate generally positive
      impacts. A trend towards improved participation in personal care, mobility,
      interpersonal relationships and play was observed. Data regarding the effect on
      the development of cognitive functions are contradictory. For the social
      environment, a positive change was observed in parents' attitudes and their own
      social participation after their child tried Assistive Technology. CONCLUSION:
      The results illustrate the complex interaction between person, environment and
      social participation. Although they are a compensatory aid, WCs do not have a
      negative impact on motor development. Finally, methodologically speaking, the
      subject seems to have been explored sufficiently to now be studied in greater
      depth by means of empirical studies generating evidence-based data.

PMID- 22455385
TI  - Topical 1% oxytetracycline hydrochloride versus placebo in oral mucosa biopsy.
AB  - BACKGROUND: Oral surgical procedures produce side effects such as pain and
      inflammation, the magnitude of which depends on the degree of tissue damage
      produced. OBJECTIVE: To explore the effectiveness and safety of the topical
      application of 1% oxytetracycline hydrochloride after biopsy of the oral mucosa.
      METHODS: A randomized, double-blind, placebo- and no treatment-controlled study
      was conducted in 90 patients with lesions needing histopathologic analysis. The
      patients were divided into three groups. Group I (control) received no treatment;
      in group II, the site of surgical intervention was treated topically with 1%
      oxytetracycline hydrochloride three times a day for 1 week; and in group III, the
      patients were treated in the same way but with placebo. Using a visual analog
      scale, we determined the time of maximum postoperative pain. RESULTS: Maximum
      pain intensity was recorded in the placebo group, with peak pain occurring 24
      hours after surgery. The pain subsequently tended to decrease gradually over the
      1-week period of the study. The maximum level of pain was significantly lower in
      group II than in the controls. No adverse effects were recorded. CONCLUSIONS:
      Topical 1% oxytetracycline hydrochloride decreases pain symptoms after oral
      mucosa biopsy.

PMID- 22455386
TI  - Effects of 2 weeks lower limb immobilization and two separate rehabilitation
      regimens on gastrocnemius muscle protein turnover signaling and normalization
      genes.
AB  - BACKGROUND: Limb immobilization causes a rapid loss of muscle mass and strength
      that requires appropriate rehabilitation to ensure restoration of normal
      function. Whereas the knowledge of muscle mass signaling with immobilization has
      increased in recent years, the molecular regulation in the rehabilitation of
      immobilization-induced muscle atrophy is only sparsely studied. To investigate
      the phosphorylation and expression of candidate key molecular muscle mass
      regulators after immobilization and subsequent rehabilitation we performed two
      separate studies. METHODS: We immobilized the lower limb for 2 weeks followed by
      the in-house hospital standard physiotherapy rehabilitation (Study 1). Secondly,
      we conducted an intervention study using the same 2 weeks immobilization protocol
      during which protein/carbohydrate supplementation was given. This was followed by
      6 weeks of rehabilitation in the form of resistance training and continued
      protein/carbohydrate supplementation (Study 2). We obtained muscle biopsies from
      the medial gastrocnemius prior to immobilization (PRE), post-immobilization
      (IMMO) and post-rehabilitation (REHAB) and measured protein expression and
      phosphorylation of Akt, mTOR, S6k, 4E-BP1, GSK3beta, ubiquitin and MURF1 and mRNA
      expression of Atrogin-1, MURF1, FOXO1, 3 and 4 as well as appropriate
      housekeeping genes. RESULTS: In both studies, no changes in protein expression or
      phosphorylation for any measured protein were observed. In Study 1, FOXO3 and
      FOXO4 mRNA expression decreased after IMMO and REHAB compared to PRE, whereas
      other mRNAs remained unchanged. Interestingly, we found significant changes in
      expression of the putative housekeeping genes GAPDH, HADHA and S26 with
      immobilization in both studies. CONCLUSIONS: In neither study, the changes in
      muscle mass associated with immobilization and rehabilitation were accompanied by
      expected changes in expression of atrophy-related genes or phosphorylation along
      the Akt axis. Unexpectedly, we observed significant changes in several of the so
      called housekeeping genes GAPDH, HADHA and S26 with immobilization in both
      studies, thereby questioning the usefulness of these genes for normalization of
      RNA data purposes in muscle immobilization studies.

PMID- 22455387
TI  - Winding up the molecular clock in the genus Carabus (Coleoptera: Carabidae):
      assessment of methodological decisions on rate and node age estimation.
AB  - BACKGROUND: Rates of molecular evolution are known to vary across taxa and among
      genes, and this requires rate calibration for each specific dataset based on
      external information. Calibration is sensitive to evolutionary model parameters,
      partitioning schemes and clock model. However, the way in which these and other
      analytical aspects affect both the rates and the resulting clade ages from
      calibrated phylogenies are not yet well understood. To investigate these aspects
      we have conducted calibration analyses for the genus Carabus (Coleoptera,
      Carabidae) on five mitochondrial and four nuclear DNA fragments with 7888 nt
      total length, testing different clock models and partitioning schemes to select
      the most suitable using Bayes Factors comparisons. RESULTS: We used these data to
      investigate the effect of ambiguous character and outgroup inclusion on both the
      rates of molecular evolution and the TMRCA of Carabus. We found considerable
      variation in rates of molecular evolution depending on the fragment studied
      (ranging from 5.02% in cob to 0.26% divergence/My in LSU-A), but also on
      analytical conditions. Alternative choices of clock model, partitioning scheme,
      treatment of ambiguous characters, and outgroup inclusion resulted in rate
      increments ranging from 28% (HUWE1) to 1000% (LSU-B and ITS2) and increments in
      the TMRCA of Carabus ranging from 8.4% (cox1-A) to 540% (ITS2). Results support
      an origin of the genus Carabus during the Oligocene in the Eurasian continent
      followed by a Miocene differentiation that originated all main extant lineages.
      CONCLUSIONS: The combination of several genes is proposed as the best strategy to
      minimise both the idiosyncratic behaviors of individual markers and the effect of
      analytical aspects in rate and age estimations. Our results highlight the
      importance of estimating rates of molecular evolution for each specific dataset,
      selecting for optimal clock and partitioning models as well as other
      methodological issues potentially affecting rate estimation.

PMID- 22455388
TI  - Histone deacetylase 3 modulates the expansion of human hematopoietic stem cells.
AB  - Epigenetic changes are regarded as emerging major players for hematopoietic stem
      cell (HSC) biology. Although some histone deacetylase (HDAC) inhibitors, such as
      valproic acid (VA), induce differentiation and apoptosis in a variety of leukemic
      cells in vitro, they produce a favorable effect on the expansion of normal HSCs.
      In this study, we have identified the VA target HDAC3 as a negative regulator of
      umbilical cord blood HSC expansion. We demonstrate that knockdown of the
      transcript dramatically improves CD34+ cell expansion, which correlates with a
      higher potential to generate colony-forming units in functional assays. We show
      that this effect is mediated at the level of primitive hematopoietic cells and
      that it is not due to negative effects on specific cell commitment or alterations
      in the cell cycle. HDAC3 inhibition does not block commitment to the monocytic
      lineage and the maturation of monocyte precursors, which are the main inhibited
      pathways in the presence of VA. Therefore, our results identify HDAC3 as a
      promising target for therapies aiming to expand HSCs.

PMID- 22455389
TI  - Localised boundary air layer and clothing evaporative resistances for individual
      body segments.
AB  - Evaporative resistance is an important parameter to characterise clothing thermal
      comfort. However, previous work has focused mainly on either total static or
      dynamic evaporative resistance. There is a lack of investigation of localised
      clothing evaporative resistance. The objective of this study was to study
      localised evaporative resistance using sweating thermal manikins. The individual
      and interaction effects of air and body movements on localised resultant
      evaporative resistance were examined in a strict protocol. The boundary air
      layer's localised evaporative resistance was investigated on nude sweating
      manikins at three different air velocity levels (0.18, 0.48 and 0.78 m/s) and
      three different walking speeds (0, 0.96 and 1.17 m/s). Similarly, localised
      clothing evaporative resistance was measured on sweating manikins at three
      different air velocities (0.13, 0.48 and 0.70 m/s) and three walking speeds (0,
      0.96 and 1.17 m/s). Results showed that the wind speed has distinct effects on
      local body segments. In contrast, walking speed brought much more effect on the
      limbs, such as thigh and forearm, than on body torso, such as back and waist. In
      addition, the combined effect of body and air movement on localised evaporative
      resistance demonstrated that the walking effect has more influence on the
      extremities than on the torso. Therefore, localised evaporative resistance values
      should be provided when reporting test results in order to clearly describe
      clothing local moisture transfer characteristics. PRACTITIONER SUMMARY: Localised
      boundary air layer and clothing evaporative resistances are essential data for
      clothing design and assessment of thermal comfort. A comprehensive understanding
      of the effects of air and body movement on localised evaporative resistance is
      also necessary by both textile and apparel researchers and industry.

PMID- 22455391
TI  - "Digitally" addressable focusing of light into a subwavelength hot spot.
AB  - We show that a plasmonic metamaterial can act as a far-field to near-field
      transformer that focuses a free-space beam of light into a subwavelength energy
      hot spot at a prescribed location with a spot size only a small fraction of the
      wavelength. The hot spot position on the metamaterial can be prescribed and moved
      at will from one metamolecule of the array to another in a "digital" fashion
      simply by modulating the input phase profile, thus providing new opportunities
      for imaging and optical data processing.

PMID- 22455392
TI  - Development and testing of hyperbaric atomic force microscopy (AFM) and
      fluorescence microscopy for biological applications.
AB  - A commercially available atomic force microscopy and fluorescence microscope were
      installed and tested inside a custom-designed hyperbaric chamber to provide the
      capability to study the effects of hyperbaric gases on biological preparations,
      including cellular mechanism of oxidative stress. In this report, we list details
      of installing and testing atomic force microscopy and fluorescence microscopy
      inside a hyperbaric chamber. The pressure vessel was designed to accommodate a
      variety of imaging equipment and ensures full functionality at ambient and
      hyperbaric conditions (<=85 psi). Electrical, gas and fluid lines were installed
      to enable remote operation of instrumentation under hyperbaric conditions, and to
      maintain viable biological samples with gas-equilibrated superfusate and/or
      drugs. Systems were installed for vibration isolation and temperature regulation
      to maintain atomic force microscopy performance during compression and
      decompression. Results of atomic force microscopy testing demonstrate sub
      nanometre resolution at hyperbaric pressure in dry scans and fluid scans, in both
      contact mode and tapping mode. Noise levels were less when measurements were
      taken under hyperbaric pressure with air, helium (He) and nitrogen (N(2) ).
      Atomic force microscopy and fluorescence microscopy measurements were made on a
      variety of living cell cultures exposed to hyperbaric gases (He, N(2) , O(2) ,
      air). In summary, atomic force microscopy and fluorescence microscopy were
      installed and tested for use at hyperbaric pressures and enables the study of
      cellular and molecular effects of hyperbaric gases and pressure per se in
      biological preparations.

PMID- 22455390
TI  - hCG, the wonder of today's science.
AB  - BACKGROUND: hCG is a wonder. Firstly, because hCG is such an extreme molecule.
      hCG is the most acidic glycoprotein containing the highest proportion of sugars.
      Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging
      from control of human pregnancy to human cancer. This review examines these
      molecules in detail. CONTENT: These 5 molecules, hCG, sulfated hCG,
      hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced
      by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1),
      and by placental cytotrophoblast cells and human malignancies (group 2). Group 1
      molecules are both hormones that act on the hCG/LH receptor. These molecules are
      central to human menstrual cycle and human pregnancy. Group 2 molecules are
      autocrines, that act by antagonizing a TGF beta receptor. These molecules are
      critical to all advanced malignancies. CONCLUSIONS: The hCG groups are molecules
      critical to both the molecules of pregnancy or human life, and to the advancement
      of cancer, or human death.

PMID- 22455393
TI  - A functional polymorphism in Pre-miR-146a is associated with susceptibility to
      gastric cancer in a Chinese population.
AB  - MicroRNAs play an important role in regulating gene expression at the post
      transcriptional level and are involved in numerous physiological processes.
      Aberrant expression of MicroRNAs is considered to participate in occurrence and
      progression of human cancers. A G>C polymorphism, rs2910164, which is located in
      the sequence of miR-146a precursor, could alter mature miR-146a expression and
      has been suggested to influence cancer risk. The present study was aimed to
      investigate whether this polymorphism has effects on susceptibility to gastric
      cancer in the Chinese population. We genotyped the miR-146a rs2910164
      polymorphism using the TaqMan method in a two-stage case-control study comprising
      a total of 1686 gastric cancer patients and 1895 cancer-free subjects. The
      logistic regression was used to assess the genetic associations with gastric
      cancer risk. We found a significant association between rs2910164 polymorphism
      and increased gastric cancer risk [p = 0.038, odds ratio (OR) = 1.26, 95%
      confidence interval (CI) = 1.01-1.56; GG vs. CC/CG]. Similar results were
      observed in a follow-up replication study. Combined data from the two studies
      generated a more significant association [p = 0.001, OR = 1.27, 95% CI = 1.10
      1.46; GG vs. CC/CG]. Besides, the increased risk associated with the rs2910164GG
      genotype was more evident in younger subjects (OR = 1.51, 95% CI = 1.25-1.81)
      rather than in older subjects. Our results suggest that the rs2910164
      polymorphism in the sequence of miR-146a precursor may influence the
      susceptibility to gastric cancer in our Chinese population.

PMID- 22455394
TI  - Potential control of human immunodeficiency virus type 1 asp expression by
      alternative splicing in the upstream untranslated region.
AB  - The negative-sense asp open reading frame (ORF) positioned opposite to the human
      immunodeficiency virus type 1 (HIV-1) env gene encodes the 189 amino acid,
      membrane-associated ASP protein. Negative-sense transcription, regulated by long
      terminal repeat sequences, has been observed early in HIV-1 infection in vitro.
      All subtypes of HIV-1 were scanned to detect the negative-sense asp ORF and to
      identify potential regulatory sequences. A series of highly conserved upstream
      short open reading frames (sORFs) was identified. This potential control region
      from HIV-1(NL4-3), containing six sORFs, was cloned upstream of the reporter gene
      EGFP. Expression by transfection of HEK293 cells indicated that the introduction
      of this sORF region inhibits EGFP reporter expression; analysis of transcripts
      revealed no significant changes in levels of EGFP mRNA. Reverse transcriptase
      polymerase chain reaction analysis (RT-PCR) further demonstrated that the
      upstream sORF region undergoes alternative splicing in vitro. The most abundant
      product is spliced to remove sORFs I to V, leaving only the in-frame sORF VI
      upstream of asp. Sequence analysis revealed the presence of typical splice donor-
      and acceptor-site motifs. Mutation of the highly conserved splice donor and
      acceptor sites modulates, but does not fully relieve, inhibition of EGFP
      production. The strong conservation of asp and its sORFs across all HIV-1
      subtypes suggests that the asp gene product may have a role in the pathogenesis
      of HIV-1. Alternative splicing of the upstream sORF region provides a potential
      mechanism for controlling expression of the asp gene.

PMID- 22455395
TI  - Association of Ku70 A-31G polymorphism and risk of renal cell carcinoma in a
      Chinese population.
AB  - The DNA repair gene Ku70 plays a key role in the DNA double-strand breaks (DSBs)
      repair system. Defects in DSBs repair capacity can lead to genomic instability.
      We hypothesized that the Ku70 A-31G polymorphism (rs132770) was associated with
      the risk of renal cell carcinoma (RCC). In a hospital-based case-control study of
      620 RCC patients and 623 cancer-free controls frequency matched by age and sex,
      we genotyped the functional polymorphism Ku70 A-31G (rs132770). Thirty-eight
      normal renal tissue samples with different genotypes were tested to estimate the
      Ku70 mRNA expression by real-time quantitative reverse transcription. Compared
      with the GG genotype, the GA and GA/AA genotypes had a significantly decreased
      risk of RCC [adjusted odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.44
      0.87 for GA, and OR = 0.62, 95% CI = 0.45-0.86 for GA/AA]. The in vivo
      experiments with normal renal tissues revealed that a statistically significantly
      higher Ku70 mRNA expression was identified in samples with GA/AA genotypes
      compared with those with GG genotypes (p = 0.001). These results suggested that
      the Ku70 A-31G polymorphism is involved in the etiology of RCC and, thus, may be
      a marker for genetic susceptibility to RCC in the Chinese populations.

PMID- 22455396
TI  - PVRL1 as a candidate gene for nonsyndromic cleft lip with or without cleft
      palate: no evidence for the involvement of common or rare variants in southern
      Han Chinese patients.
AB  - The poliovirus receptor related-1 (PVRL1) gene encodes nectin-1, a cell-cell
      adhesion molecule (OMIM #600644), and is mutated in the cleft lip with or without
      cleft palate/ectodermal dysplasia-1 syndrome (CLPED1, OMIM #225000). In addition,
      PVRL1 mutations have been associated with nonsyndromic cleft lip with or without
      a cleft palate (NSCL/P) in studies of multiethnic samples. To investigate the
      possible involvement of this gene in southern Han Chinese NSCL/P patients, we
      performed (i) a case-control association study, and (ii) a resequencing study. A
      set of 470 patients with NSCL/P and 693 controls were recruited, and a total of
      45 tagging single-nucleotide polymorphisms (SNPs) were genotyped by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry. In the
      resequencing study, the coding regions of the PVRL1 alpha isoform were direct
      sequenced in 45 trios from multiply affected families. One (rs7128327) of the 45
      tested SNPs showed a trend toward statistical significance in the genotypic-level
      chi-square test (p = 0.009567). However, this result did not withstand correction
      for multiple testing. Likewise, sliding window haplotype analyses consisting of
      two, three, or four SNPs failed to detect any positive association. Resequencing
      analysis also failed to identify any novel rare sequence variants. In conclusion,
      the present study provided no support for the hypothesis that common or rare
      variants in PVRL1 play a significant role in NSCL/P development in the southern
      Han Chinese population. This is the first study that has used tagging SNPs
      covering all the coding and noncoding regions to search for common NSCL/P
      associated mutations of PVRL1.

PMID- 22455397
TI  - Influence of the solvent and metal center on supramolecular chirality induction
      with bisporphyrin tweezer receptors. Strong metal modulation of effective
      molarity values.
AB  - We describe the synthesis of a bisporphyrin tweezer receptor 1.H(4) and its
      metalation with Zn(II) and Rh(III) cations. We report the thermodynamic
      characterization of the supramolecular chirality induction process that takes
      place when the metalated bisporphyrin receptors coordinate to enantiopure 1,2
      diaminocyclohexane in two different solvents, toluene and dichloromethane. We
      also performed a thorough study of several simpler systems that were used as
      models for the thermodynamic characterization of the more complex bisporphyrin
      systems. The initial complexation of the chiral diamine with the bisporphyrins
      produces a 1:1 sandwich complex that opens up to yield a simple 1:2 complex in
      the presence of excess diamine. The CD spectra associated with the 1:1 and 1:2
      complexes of both metalloporphyrins, 1.Zn(2) and 1.Rh(2), display bisignate
      Cotton effects when the chirogenesis process is studied in toluene solutions. On
      the contrary, in dichloromethane solutions, only 1.Zn(2) yields CD-active 1:1 and
      1:2 complexes, while the 1:2 complex of 1.Rh(2) is CD-silent. In both solvents,
      porphyrin 1.Zn(2) features a stoichiometrically controlled chirality inversion
      process, which is the sign of the Cotton effect of the 1:1 complex is opposite to
      that of the 1:2 complex. In contrast, porphyrin 1.Rh(2) affords 1:1 and 1:2
      complexes in toluene solutions with the same sign for their CD couplets.
      Interestingly, in both solvents, the signs of the CD couplets associated with the
      1:1 sandwich complexes of 1.Zn(2) and 1.Rh(2) are opposite. The amplitudes of the
      CD couplets are higher for 1.Zn(2) than for 1.Rh(2). This observation is in
      agreement with 1.Rh(2) having a smaller extinction coefficient than 1.Zn(2). We
      performed DFT-based calculations and assigned molecular structures to the 1:1 and
      1:2 complexes that explain the observed signs for their CD couplets.
      Unexpectedly, the quantification of the thermodynamic stability of the two
      metallobisporphyrin/diamine 1:1 sandwich complexes revealed the existence of
      interplay between effective molarity values (EM) and the strength of the
      intermolecular interaction (K(m); N...Zn or N...Rh) used in their assembly. The
      EM for the N...Rh(III) intramolecular interaction is 3 orders of magnitude
      smaller than that for the N...Zn(II) interaction, both of which are embedded in
      the same scaffold of the 1.M(2) bisporphyrin receptor.

PMID- 22455398
TI  - Exploration of pipecolate sulfonamides as binders of the FK506-binding proteins
      51 and 52.
AB  - FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal
      transduction of steroid hormone receptors. Single nucleotide polymorphisms in the
      gene encoding FKBP51 have been associated with a variety of psychiatric
      disorders. Rapamycin and FK506 are two macrocyclic natural products, which
      tightly bind to most FKBP family members, including FKBP51 and FKBP52. A
      bioisosteric replacement of the alpha-ketoamide moiety of rapamycin and FK506
      with a sulfonamide was envisaged with the retention of the conserved hydrogen
      bonds. A focused solid support-based synthesis protocol was developed, which led
      to ligands with submicromolar affinity for FKBP51 and FKBP52. The molecular
      binding mode for one sulfonamide analogue was confirmed by X-ray crystallography.

PMID- 22455399
TI  - Reciprocal cooperation between unrelated rats depends on cost to donor and
      benefit to recipient.
AB  - BACKGROUND: Although evolutionary models of cooperation build on the intuition
      that costs of the donor and benefits to the receiver are the most general
      fundamental parameters, it is largely unknown how they affect the decision of
      animals to cooperate with an unrelated social partner. Here we test
      experimentally whether costs to the donor and need of the receiver decide about
      the amount of help provided by unrelated rats in an iterated prisoner's dilemma
      game. RESULTS: Fourteen unrelated Norway rats were alternately presented to a
      cooperative or defective partner for whom they could provide food via a
      mechanical apparatus. Direct costs for this task and the need of the receiver
      were manipulated in two separate experiments. Rats provided more food to
      cooperative partners than to defectors (direct reciprocity). The propensity to
      discriminate between helpful and non-helpful social partners was contingent on
      costs: An experimentally increased resistance in one Newton steps to pull food
      for the social partner reduced the help provided to defectors more strongly than
      the help returned to cooperators. Furthermore, test rats provided more help to
      hungry receivers that were light or in poor condition, which might suggest
      empathy, whereas this relationship was inverse when experimental partners were
      satiated. CONCLUSIONS: In a prisoner's dilemma situation rats seem to take effect
      of own costs and potential benefits to a receiver when deciding about helping a
      social partner, which confirms the predictions of reciprocal cooperation. Thus,
      factors that had been believed to be largely confined to human social behaviour
      apparently influence the behaviour of other social animals as well, despite
      widespread scepticism. Therefore our results shed new light on the biological
      basis of reciprocity.

PMID- 22455400
TI  - Quantum dot/carrier-protein/haptens conjugate as a detection nanobioprobe for
      FRET-based immunoassay of small analytes with all-fiber microfluidic biosensing
      platform.
AB  - This study demonstrates the use of carrier-protein/haptens conjugate (e.g.,
      BSA/2,4-dichlorophenoxyacetic acid, 2,4-D-BSA) for biological modification of
      quantum dots (QDs) for the detection of small analytes. Bioconjugated QDs, which
      are used as a detection nanoimmunoprobe, were prepared through conjugating
      carboxyl QDs with 2,4-D-BSA conjugate. Based on the principle of quantum dot
      fluorescence resonance energy transfer (QD-FRET), an all-fiber microfluidic
      biosensing platform has been developed for investigating FRET efficiency,
      immunoassay mechanism and format, and binding kinetics between QD immunoprobe and
      fluorescence labeled anti-2,4-D monoclonal antibody. The structure of multiplex
      haptens/BSA conjugate coupling to QD greatly improves the FRET efficiency and the
      sensitivity of the nanosensor. With a competitive detection mode, samples
      containing different concentrations of 2,4-D were incubated with a given
      concentration of QD immunoprobe and fluorescence-labeled antibody, and then
      detected by the all-fiber microfluidic biosensing platform. A higher
      concentration of 2,4-D led to less fluorescence-labeled anti-2,4-D antibody bound
      to the QD immunoprobe surface and, thus, a lower fluorescence signal. The
      quantification of 2,4-D over concentration ranges from 0.5 nM to 3 MUM with a
      detection limit determined as 0.5 nM. The performance of the nanosensor with
      spiked real water samples showed good recovery, precision, and accuracy,
      indicating that it was less suspectable to water matrix effects. With the use of
      different QD nanobioprobes modified by other carrier-protein/haptens conjugates,
      this biosensing protocol based on QD-FRET can be potentially applied for on-site,
      real-time, inexpensive, and easy-to-use monitoring of other trace analytes.

PMID- 22455401
TI  - Endogenous hydrogen sulfide insufficiency as a predictor of sexual dysfunction in
      aging rats.
AB  - OBJECTIVE: Our earlier studies showed that endogenous hydrogen sulfide (H(2)S)
      pathway contributed significantly to erectile function. In this study, we tested
      the hypothesis that age-dependent changes in the bioavailability of H(2)S
      increased the risk of erectile dysfunction (ED). METHODS: Young, adult (3-month)
      and older (18-month) male Sprague-Dawley rats (n = 6-8/group) were treated daily
      with sodium hydrosulfide hydrate (NaHS), DL-propargylglycine, sildenafil or l
      NAME for 10 weeks. Subsequent to cavernous nerve electrical stimulation,
      intracavernosal pressure (ICP) responses were determined, and the samples were
      collected and processed for hormonal (plasma) and gaseous parameters (plasma and
      erectile corpus cavernosum [CC]) using standard assay protocols. RESULTS: Aging
      significantly reduced the ICP response (35.9 +/- 2.0 mmHg vs. 45.2 +/- 1.9 mmHg
      in young controls), which was countered by NaHS (53.5 +/- 6.0) or sildenafil
      (52.8 +/- 9.8) treatment. In these rats, marked increments to testosterone (T) or
      estradiol resulted from NaHS supplementation. Similar to age-dependent decline in
      NO, the plasma and CC level of H(2)S was significantly lower in senescent rats
      when compared with young animals (p < 0.05). CONCLUSION: Our results confirm that
      ED with aging may be linked to a derangement in the H(2)S pathway accompanied by
      low T levels. It is likely that a pharmacologic intervention delivering H(2)S
      will provide additional benefits to sexual function from an improved T milieu.

PMID- 22455402
TI  - Working toward a sustainable system of asthma care: development of the School
      Based Preventive Asthma Care Technology (SB-PACT) trial.
AB  - OBJECTIVE: We previously conducted the School-Based Asthma Therapy trial to
      improve adherence to national asthma guidelines for urban children through
      directly observed administration of preventive asthma medications in school. The
      trial successfully improved outcomes among these children; however, several
      factors limit its potential for dissemination. To enhance sustainability, we
      subsequently developed a new model of care using web-based guides for efficient
      communications and integration within school and community systems. This article
      describes the development of the School-Based Preventive Asthma Care Technology
      (SB-PACT) trial. METHOD: We developed the SB-PACT web-based system based on
      stakeholder feedback, and conducted a pilot randomized trial with 100 children to
      establish its feasibility in facilitating preventive asthma care for high-risk
      children. The SB-PACT system represents a new model of care using web-based
      guides for asthma symptom screening, follow-up control assessments, and
      electronic communications with providers. RESULT: We enrolled and successfully
      screened all children using the web-based system. Most providers used the
      electronic communication system without difficulty, and the majority of children
      in the intervention group received preventive medications through school as
      planned and dose adjustments as needed. Several challenges to implementation also
      were encountered. CONCLUSIONS: This program is designed to promote sustainability
      of school-based asthma care, reduce program costs, and ultimately succeed in a
      real-world setting. With further refinements, it has the potential to be
      implemented nationally in schools.

PMID- 22455403
TI  - Satisfaction with the treatment, confidence and 'naturalness' in engaging in
      sexual activity in men with psychogenic erectile dysfunction: preliminary results
      of a randomized controlled trial of three therapeutic approaches.
AB  - OBJECTIVE: To assess the efficacy of group psychotherapy (GTP) and/or sildenafil
      for psychogenic erectile dysfunction (ED). PATIENTS AND METHODS: A randomized
      controlled single-blind trial was performed at the Institute of Psychiatry of the
      Medical School of at Universidade de Sao Paulo, Sao Paulo, Brazil. In all, 30 men
      with mild and moderate psychogenic ED were randomized to receive for 6 months:
      GPT plus 50 mg sildenafil on-demand, or 50 mg sildenafil on-demand exclusively,
      or GPT exclusively. Changes in score from baseline for three questions of the
      Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) were evaluated
      at endpoint and after 3-months follow-up. RESULTS: Satisfaction with the
      treatment, confidence and 'naturalness' increased in the GPT plus sildenafil and
      GPT exclusively groups (P= 0.001) from baseline to endpoint. The treatment-by
      time comparison was not significant at endpoint vs the 3-month follow-up, in the
      three groups. There was no difference in the sildenafil group in the three study
      periods (P > 0.05) CONCLUSION: Men with mild and moderate psychogenic ED had
      higher treatment satisfaction, confidence and naturalness in engaging in sexual
      activity when receiving GPT plus sildenafil or GP exclusively, when compared with
      sildenafil exclusively, as assessed by these three EDITS questions after 6-months
      treatment.

PMID- 22455404
TI  - Preperitoneal repair of inguinal hernia.
AB  - From 2007 to date, fi ve boys with bladder exstrophy underwent this pre-emptive
      treatment of inguinal hernia at our institution. None has developed a recurrence
      after a median (range) follow-up of 29 (5 - 46) months. This approach avoids any
      manipulation of the inguinal canal, which is an advantage per se, but may be even
      more important in children with bladder exstrophy given the relatively high risk
      of hernia recurrence reported [ 1,2 ] . Furthermore, the presence of a pelvic
      diastasis makes the pelvic dissection of the cord easier than in normal children
      with a closed pelvic ring. The same procedure can also possibly be performed in
      children with a congenital inguinal hernia undergoing other procedures that
      require dissection of the perivesical space, e.g. ureteric re-implantation or
      ureterocoele repair.

PMID- 22455405
TI  - Reply.

PMID- 22455406
TI  - Cost-effectiveness of standard vs intensive antibiotic regimens for transrectal
      ultrasonography (TRUS)-guided prostate biopsy prophylaxis.

PMID- 22455408
TI  - Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT)
      with experienced surgeons performing complete resections and obtaining detrusor
      muscle reduces early recurrence in new non-muscle-invasive bladder cancer:
      validation across time and place and recommendation for benchmarking.

PMID- 22455410
TI  - Obesity and urological conditions: part two: the intervention.

PMID- 22455411
TI  - Tropical lymphedemas--control and prevention.

PMID- 22455412
TI  - Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis.
AB  - BACKGROUND: In this phase 2, randomized, double-blind, placebo-controlled, dose
      ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a
      human anti-interleukin-17-receptor monoclonal antibody, for the treatment of
      moderate-to-severe plaque psoriasis. METHODS: We randomly assigned patients with
      a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which
      scores range from 0 to 72, with higher scores indicating more severe disease) and
      with 10% or more of their body-surface area affected by psoriasis to receive
      brodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or
      280 mg monthly) or placebo. The primary end point was the percentage improvement
      from baseline in the PASI score at week 12. Secondary end points included
      improvement of at least 75% and at least 90% in the PASI score and the score on
      the static physician's global assessment at week 12. RESULTS: A total of 198
      patients underwent randomization. At week 12, the mean percentage improvements in
      the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9%
      among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among
      those receiving 280 mg, and 16.0% among those receiving placebo (P<0.001 for all
      comparisons with placebo). An improvement of at least 75% and at least 90% in the
      PASI score at week 12 was seen in 77% and 72%, respectively, of the patients in
      the 140-mg brodalumab group and in 82% and 75%, respectively, of the patients in
      the 210-mg group, as compared with 0% in the placebo group (P<0.001 for all
      comparisons). The percentage of patients with a static physician's global
      assessment of clear or minimal disease was 26%, 85%, 80%, and 69% with the 70-mg,
      140-mg, 210-mg, and 280-mg doses, respectively, of brodalumab, as compared with
      3% with placebo (P<0.01 for all comparisons with placebo). Two cases of grade 3
      neutropenia were reported in the 210-mg brodalumab group. The most commonly
      reported adverse events in the combined brodalumab groups were nasopharyngitis
      (8%), upper respiratory tract infection (8%), and injection-site erythema (6%).
      CONCLUSIONS: Brodalumab significantly improved plaque psoriasis in this 12-week,
      phase 2 study. (Funded by Amgen; ClinicalTrials.gov number, NCT00975637.).

PMID- 22455413
TI  - Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis.
AB  - BACKGROUND: Type 17 helper T cells have been suggested to play a pathological
      role in psoriasis. They secrete several proinflammatory cytokines, including
      interleukin-17A (also known as interleukin-17). We evaluated the safety and
      efficacy of ixekizumab (LY2439821), a humanized anti-interleukin-17 monoclonal
      antibody, for psoriasis treatment. METHODS: In our phase 2, double-blind, placebo
      controlled trial, we randomly assigned 142 patients with chronic moderate-to
      severe plaque psoriasis to receive subcutaneous injections of 10, 25, 75, or 150
      mg of ixekizumab or placebo at 0, 2, 4, 8, 12, and 16 weeks. The primary end
      point was the proportion of patients with reduction in the psoriasis area-and
      severity index (PASI) score by at least 75% at 12 weeks. Secondary end points
      included the proportion of patients with reduction in the PASI score by at least
      90% or by 100%. RESULTS: At 12 weeks, the percentage of patients with a reduction
      in the PASI score by at least 75% was significantly greater with ixekizumab
      (except with the lowest, 10-mg dose)--150 mg (82.1%), 75 mg (82.8%), and 25 mg
      (76.7%)--than with placebo (7.7%, P<0.001 for each comparison), as was the
      percentage of patients with a reduction in the PASI score by at least 90%: 150 mg
      (71.4%), 75 mg (58.6%), and 25 mg (50.0%) versus placebo (0%, P<0.001 for each
      comparison). Similarly, a 100% reduction in the PASI score was achieved in
      significantly more patients in the 150-mg group (39.3%) and the 75-mg group
      (37.9%) than in the placebo group (0%) (P<0.001 for both comparisons).
      Significant differences occurred at as early as 1 week and were sustained through
      20 weeks. Adverse events occurred in 63% of patients in both the combined
      ixekizumab groups and in the placebo group. No serious adverse events or major
      cardiovascular events were observed. CONCLUSIONS: Use of a humanized anti
      interleukin-17 monoclonal antibody, ixekizumab, improved the clinical symptoms of
      psoriasis. Further studies are needed to establish its long-term safety and
      efficacy in patients with psoriasis. (Funded by Eli Lilly; ClinicalTrials.gov
      number, NCT01107457.).

PMID- 22455414
TI  - HLA class II locus and susceptibility to podoconiosis.
AB  - BACKGROUND: Podoconiosis is a tropical lymphedema resulting from long-term
      barefoot exposure to red-clay soil derived from volcanic rock. The World Health
      Organization recently designated it as a neglected tropical disease. Podoconiosis
      develops in only a subgroup of exposed people, and studies have shown familial
      clustering with high heritability (63%). METHODS: We conducted a genomewide
      association study of 194 case patients and 203 controls from southern Ethiopia.
      Findings were validated by means of family-based association testing in 202
      family trios and HLA typing in 94 case patients and 94 controls. RESULTS: We
      found a genomewide significant association of podoconiosis with the single
      nucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the HLA-DQA1 locus
      (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to
      3.26; P=1.42*10(-9); and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to
      2.90; P=3.44*10(-8)), and suggestive associations (P<1.0*10(-5)) with seven other
      SNPs in or near HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations
      using family-based association testing. HLA typing showed the alleles HLA
      DRB1*0701 (odds ratio, 2.00), DQA1*0201 (odds ratio, 1.91), and DQB1*0202 (odds
      ratio, 1.79) and the HLA-DRB1*0701-DQB1*0202 haplotype (odds ratio, 1.92) were
      risk variants for podoconiosis. CONCLUSIONS: Association between variants in HLA
      class II loci with podoconiosis (a noncommunicable disease) suggests that the
      condition may be a T-cell-mediated inflammatory disease and is a model for gene
      environment interactions that may be relevant to other complex genetic disorders.
      (Funded by the Wellcome Trust and others.).

PMID- 22455416
TI  - Endoscopic treatment of primary vesicoureteral reflux.

PMID- 22455417
TI  - Diabetic retinopathy.

PMID- 22455418
TI  - Images in clinical medicine. Fordyce's Angiokeratomas.

PMID- 22455419
TI  - Case records of the Massachusetts General Hospital. Case 10-2012. A 16-year-old
      boy with epigastric pain and a mediastinal mass.

PMID- 22455420
TI  - To be 17 again--anti-interleukin-17 treatment for psoriasis.

PMID- 22455422
TI  - Transfusion thresholds in high-risk patients after hip surgery.

PMID- 22455423
TI  - Transfusion thresholds in high-risk patients after hip surgery.

PMID- 22455424
TI  - Transfusion thresholds in high-risk patients after hip surgery.

PMID- 22455426
TI  - Niacin in cardiovascular patients receiving statins.

PMID- 22455428
TI  - Bevacizumab in ovarian cancer.

PMID- 22455415
TI  - Lifestyle change and mobility in obese adults with type 2 diabetes.
AB  - BACKGROUND: Adults with type 2 diabetes mellitus often have limitations in
      mobility that increase with age. An intensive lifestyle intervention that
      produces weight loss and improves fitness could slow the loss of mobility in such
      patients. METHODS: We randomly assigned 5145 overweight or obese adults between
      the ages of 45 and 74 years with type 2 diabetes to either an intensive lifestyle
      intervention or a diabetes support-and-education program; 5016 participants
      contributed data. We used hidden Markov models to characterize disability states
      and mixed-effects ordinal logistic regression to estimate the probability of
      functional decline. The primary outcome was self-reported limitation in mobility,
      with annual assessments for 4 years. RESULTS: At year 4, among 2514 adults in the
      lifestyle-intervention group, 517 (20.6%) had severe disability and 969 (38.5%)
      had good mobility; the numbers among 2502 participants in the support group were
      656 (26.2%) and 798 (31.9%), respectively. The lifestyle-intervention group had a
      relative reduction of 48% in the risk of loss of mobility, as compared with the
      support group (odds ratio, 0.52; 95% confidence interval, 0.44 to 0.63; P<0.001).
      Both weight loss and improved fitness (as assessed on treadmill testing) were
      significant mediators of this effect (P<0.001 for both variables). Adverse events
      that were related to the lifestyle intervention included a slightly higher
      frequency of musculoskeletal symptoms at year 1. CONCLUSIONS: Weight loss and
      improved fitness slowed the decline in mobility in overweight adults with type 2
      diabetes. (Funded by the Department of Health and Human Services and others;
      ClinicalTrials.gov number, NCT00017953.).

PMID- 22455429
TI  - Bevacizumab in ovarian cancer.

PMID- 22455430
TI  - Bevacizumab in ovarian cancer.

PMID- 22455432
TI  - Coronary arteries, myocardial infarction, and history.

PMID- 22455433
TI  - Coronary arteries, myocardial infarction, and history.

PMID- 22455438
TI  - Images in clinical medicine. Intestinal infestation with Ancylostoma ceylanicum.

PMID- 22455439
TI  - Addition of indoles to oxyallyl cations for facile access to alpha-indole
      carbonyl compounds.
AB  - A direct coupling of unprotected indoles and alpha-halo ketones via in situ
      generated oxyallyl cation intermediates is described. The reactions efficiently
      afford alpha-indole carbonyl compounds with good to quantitative yields.

PMID- 22455441
TI  - Polyvalent side chain peptide-synthetic polymer conjugates as HIV-1 entry
      inhibitors.
AB  - This report describes the synthesis and properties of a series of polyvalent side
      chain peptide-synthetic polymer conjugates designed to block the CD4 binding site
      on gp120 and inhibit HIV-1 entry into a host cell. The peptide sequences in the
      conjugates are based on the CDR H3 region of the neutralizing anti-HIV-1 antibody
      IgG1 b12. Using a consecutive ester-amide/thiol-ene postpolymerization
      modification strategy, a library of polymer conjugates was prepared. Evaluation
      of the HIV-1 inhibitory properties revealed that midsized polymer conjugates
      displayed the highest antiviral activity, while shorter and longer conjugates
      proved to be less efficacious inhibitors. The lower molecular weight conjugates
      may not have sufficient length to span the distance between two neighboring gp120
      containing spikes, while the higher molecular weight conjugates may be
      compromised due to a higher entropic penalty that would accompany their binding
      to the viral envelope. Although the IC(50) values for these polymer conjugates
      are higher than that of the parent IgG1 b12 antibody, the strategy presented here
      may represent an interesting antiviral approach due to the attractive properties
      of such polymer therapeutics (relatively inexpensive production and purification
      costs, high thermal and chemical stability in storage conditions, long half-life
      in biological tissues, low immunogenicity, and protection from proteolytic
      degradation).

PMID- 22455440
TI  - Modifiable risk factors associated with bone deficits in childhood cancer
      survivors.
AB  - BACKGROUND: To determine the prevalence and severity of bone deficits in a cohort
      of childhood cancer survivors (CCS) compared to a healthy sibling control group,
      and the modifiable factors associated with bone deficits in CCS. METHODS: Cross
      sectional study of bone health in 319 CCS and 208 healthy sibling controls. Bone
      mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA).
      Generalized estimating equations were used to compare measures between CCS and
      controls. Among CCS, multivariable logistic regression was used to evaluate odds
      ratios for BMD Z-score <= -1. RESULTS: All subjects were younger than 18 years of
      age. Average time since treatment was 10.1 years (range 4.3 - 17.8 years). CCS
      were 3.3 times more likely to have whole body BMD Z-score <= -1 than controls
      (95% CI: 1.4-7.8; p = 0.007) and 1.7 times more likely to have lumbar spine BMD Z
      score <= -1 than controls (95% CI: 1.0-2.7; p = 0.03). Among CCS, hypogonadism,
      lower lean body mass, higher daily television/computer screen time, lower
      physical activity, and higher inflammatory marker IL-6, increased the odds of
      having a BMD Z-score <= -1. CONCLUSIONS: CCS, less than 18 years of age, have
      bone deficits compared to a healthy control group. Sedentary lifestyle and
      inflammation may play a role in bone deficits in CCS. Counseling CCS and their
      caretakers on decreasing television/computer screen time and increasing activity
      may improve bone health.

PMID- 22455443
TI  - Symptoms of testosterone deficiency in early middle aged men.
AB  - Symptoms of testosterone deficiency and concentrations of testosterone (T) and
      bioavailable testosterone (BT) were studied in 35- and 45-year-old men. METHODS:
      A questionnaire, was sent to all 35- and 45-year-old men in Linkoping, Sweden
      (n=1998). The questionnaire has earlier been used for 55- to 75-year-old men and
      included demographic data, medical history, different symptoms possibly of T
      deficiency and the 10 questions from the "ADAM-questionnaire". Totally 200 men
      randomly selected among the men who answered the questionnaire were asked to give
      blood samples for analysis of T- and BT-concentrations. RESULTS: A total of 38.7%
      of the questionnaires were returned and analysed, and 43.5% of the 200 randomly
      selected men gave blood samples. The older age group reported more symptoms that
      may be connected to low B and BT and had lower T- and BT-concentrations. Less
      strong erections and higher alcohol consumption were associated with lower
      concentrations of BT in 45-year-old men. CONCLUSIONS: The burden of symptoms
      possibly related to low T concentrations were higher in 45-year-old men, and BT
      and T were lower. However, due to the low answer frequency and number of blood
      samples analyzed no general conclusions can be drawn.

PMID- 22455442
TI  - Involvement of Src family of kinases and cAMP phosphodiesterase in the
      luteinizing hormone/chorionic gonadotropin receptor-mediated signaling in the
      corpus luteum of monkey.
AB  - BACKGROUND: In higher primates, during non-pregnant cycles, it is indisputable
      that circulating LH is essential for maintenance of corpus luteum (CL) function.
      On the other hand, during pregnancy, CL function gets rescued by the LH analogue,
      chorionic gonadotropin (CG). The molecular mechanisms involved in the control of
      luteal function during spontaneous luteolysis and rescue processes are not
      completely understood. Emerging evidence suggests that LH/CGR activation triggers
      proliferation and transformation of target cells by various signaling molecules
      as evident from studies demonstrating participation of Src family of tyrosine
      kinases (SFKs) and MAP kinases in hCG-mediated actions in Leydig cells. Since
      circulating LH concentration does not vary during luteal regression, it was
      hypothesized that decreased responsiveness of luteal cells to LH might occur due
      to changes in LH/CGR expression dynamics, modulation of SFKs or interference with
      steroid biosynthesis. METHODS: Since, maintenance of structure and function of CL
      is dependent on the presence of functional LH/CGR its expression dynamics as well
      as mRNA and protein expressions of SFKs were determined throughout the luteal
      phase. Employing well characterized luteolysis and CL rescue animal models,
      activities of SFKs, cAMP phosphodiesterase (cAMP-PDE) and expression of SR-B1 (a
      membrane receptor associated with trafficking of cholesterol ester) were
      examined. Also, studies were carried out to investigate the mechanisms
      responsible for decline in progesterone biosynthesis in CL during the latter part
      of the non-pregnant cycle. RESULTS AND DISCUSSION: The decreased responsiveness
      of CL to LH during late luteal phase could not be accounted for by changes in
      LH/CGR mRNA levels, its transcript variants or protein. Results obtained
      employing model systems depicting different functional states of CL revealed
      increased activity of SFKs [pSrc (Y-416)] and PDE as well as decreased expression
      of SR-B1 correlating with initiation of spontaneous luteolysis. However, CG, by
      virtue of its heroic efforts, perhaps by inhibition of SFKs and PDE activation,
      prevents CL from undergoing regression during pregnancy. CONCLUSIONS: The results
      indicated participation of activated Src and increased activity of cAMP-PDE in
      the control of luteal function in vivo. That the exogenous hCG treatment caused
      decreased activation of Src and cAMP-PDE activity with increased circulating
      progesterone might explain the transient CL rescue that occurs during early
      pregnancy.

PMID- 22455444
TI  - Evaluation of synthetic FK506 analogues as ligands for the FK506-binding proteins
      51 and 52.
AB  - The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the
      signal transduction of steroid hormone receptors. Both proteins have been
      implicated in prostate cancer. Furthermore, single nucleotide polymorphisms in
      the gene encoding FKBP51 have been associated with a variety of psychiatric
      disorders. Rapamycin and FK506 are two macrocyclic natural products that bind to
      these proteins indiscriminately but with nanomolar affinity. We here report the
      cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived
      from FK506 and the first structure-activity relationship analysis for FKBP51 and
      FKBP52 based on this compound. In particular, the tert-pentyl group of this
      ligand was systematically replaced by a cyclohexyl ring system, which more
      closely resembles the pyranose ring in the high-affinity ligands rapamycin and
      FK506. The interaction with FKBPs was found to be surprisingly tolerant to the
      stereochemistry of the attached cyclohexyl substituents. The molecular basis for
      this tolerance was elucidated by X-ray cocrystallography.

PMID- 22455446
TI  - Detection and speciation of brominated flame retardants in high-impact
      polystyrene (HIPS) polymers.
AB  - Polymeric materials have been suggested as possible environmental sources of
      persistent organic pollutants such as flame retardants. In situ, micrometre-scale
      characterization techniques for polymer matrix containing flame retardants may
      provide some insight into the dominant environmental transfer mechanism(s) of
      these brominated compounds. In this work, we demonstrate that micro X-ray
      fluorescence spectroscopy (MUXRF), focused ion beam scanning electron microscopy
      (FIB-SEM) combined with energy dispersive X-ray spectroscopy (EDS), and time-of
      flight secondary ion mass spectrometry (ToF-SIMS) are promising techniques for
      the elemental and chemical identification of brominated fire retardant compounds
      (such as the deca-congener of polybrominated diphenyl ether, BDE-209) within
      polymeric materials (e.g. high-impact polystyrene or HIPS). Data from MUXRF
      demonstrated that bromine (Br) inclusions were evenly distributed throughout the
      HIPS samples, whereas FIB SEM-EDS analysis revealed that small antimony (Sb) and
      Br inclusions are present, and regionally higher concentrations of Br surround
      the Sb inclusions (compared to the bulk material). Four prominent mass-to-charge
      ratio peaks (m/z 485, 487, 489 and 491) that correspond to BDE-209 were
      identified by ToF-SIMS and can be used to chemically distinguish this molecule on
      the surface of polymeric materials with respect to other brominated organic
      molecules. These techniques can be important in any study that investigates the
      route of entry to the environmental surroundings of BDE-containing materials.

PMID- 22455445
TI  - Identification of bovine leukemia virus tax function associated with host cell
      transcription, signaling, stress response and immune response pathway by
      microarray-based gene expression analysis.
AB  - BACKGROUND: Bovine leukemia virus (BLV) is associated with enzootic bovine
      leukosis and is closely related to human T-cell leukemia virus type I. The Tax
      protein of BLV is a transcriptional activator of viral replication and a key
      contributor to oncogenic potential. We previously identified interesting mutant
      forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation
      effects on BLV replication and propagation. However, the effects of these
      mutations on functions other than transcriptional activation are unknown. In this
      study, to identify genes that play a role in the cascade of signal events
      regulated by wild-type and mutant Tax proteins, we used a large-scale host cell
      gene-profiling approach. RESULTS: Using a microarray containing approximately
      18,400 human mRNA transcripts, we found several alterations after the expression
      of Tax proteins in genes involved in many cellular functions such as
      transcription, signal transduction, cell growth, apoptosis, stress response, and
      immune response, indicating that Tax protein has multiple biological effects on
      various cellular environments. We also found that TaxD247G strongly regulated
      more genes involved in transcription, signal transduction, and cell growth
      functions, contrary to TaxS240P, which regulated fewer genes. In addition, the
      expression of genes related to stress response significantly increased in the
      presence of TaxS240P as compared to wild-type Tax and TaxD247G. By contrast, the
      largest group of downregulated genes was related to immune response, and the
      majority of these genes belonged to the interferon family. However, no
      significant difference in the expression level of downregulated genes was
      observed among the Tax proteins. Finally, the expression of important cellular
      factors obtained from the human microarray results were validated at the RNA and
      protein levels by real-time quantitative reverse transcription-polymerase chain
      reaction and western blotting, respectively, after transfecting Tax proteins into
      bovine cells and human HeLa cells. CONCLUSION: A comparative analysis of wild
      type and mutant Tax proteins indicates that Tax protein exerts a significant
      impact on cellular functions as diverse as transcription, signal transduction,
      cell growth, stress response and immune response. Importantly, our study is the
      first report that shows the extent to which BLV Tax regulates the innate immune
      response.

PMID- 22455447
TI  - Validation of the Skindex-16 questionnaire in patients with skin diseases in
      Morocco.
AB  - OBJECTIVE: The aim of the study was to translate and adapt the original version
      of the Skindex-16 questionnaire from English to Moroccan Arabic language,
      refining its terms and adapting it to Moroccan culture. METHODS: After
      translation and cross-cultural adaptation, the questionnaire was tested on skin
      diseases patients. Internal consistency was tested using Cronbach's alpha
      coefficient, the test-retest reliability using intraclass correlation coefficient
      (ICC). Construct validity was assessed by examining item convergent and divergent
      validity. RESULTS: The questionnaire was administered to 120 patients. The mean
      age of patients was 39 years (SD: 16), 49.6% were married. 76.9% of all
      participants lived in an urban area. The average time to complete the Skindex-16
      questionnaire was 5 min. Questionnaire reliability was assessed using Cronbach's
      alpha coefficient, in which the values were all > 0.7. All items exceeded the 0.4
      criterion for convergent validity. CONCLUSION: In general, the findings of this
      study indicated that the authors have developed a semantically equivalent
      translation of Skindex-16 into Moroccan Arabic. It is a reliable and valid
      measure of the effects of skin disease on the quality of life in Moroccan
      patients.

PMID- 22455448
TI  - Osseointegrated dental implants in patients with intellectual disability: a pilot
      study.
AB  - PURPOSE: The objective of this study was to investigate if intellectual
      disability (ID) itself constitutes an absolute contraindication to oral
      rehabilitation with osseointegrated implants, or if adequately selected patients
      can benefit from this dental treatment technique. METHOD: We report a series of
      eight patients with non-syndromic ID and no associated neuromuscular disorders,
      craniofacial abnormalities, or serious systemic complications, in whom oral
      rehabilitation was performed using implant-supported prostheses, with a follow-up
      of one to three years. RESULTS: A total of 18 titanium implants were inserted and
      nine implant-supported prostheses were constructed. Follow-up examination showed
      that although the majority of implants presented a degree of peri-implant
      mucositis, all were osseointegrated and the prostheses were functional.
      CONCLUSIONS: Although there is very little literature on this subject, the
      results of this pilot study allow us to suggest that osseointegrated oral
      implants could constitute a therapeutic option for patients with ID. The success
      of oral rehabilitation depends fundamentally on appropriate patient selection.
      IMPLICATIONS FOR REHABILITATION: * Apart from the obvious difficulties related to
      eating and communication, edentulism is of great cosmetic importance in patients
      with ID in terms of social acceptance. * It has been suggested that patients with
      ID do not receive the same level of dental treatment as the general population. *
      The results of this pilot study allow us to suggest that osseointegrated oral
      implants could constitute a therapeutic option for patients with ID.

PMID- 22455449
TI  - Conductivity for soot sensing: possibilities and limitations.
AB  - In this study we summarize the possibilities and limitations of a conductometric
      measurement principle for soot sensing. The electrical conductivity of different
      carbon blacks (FW 200, lamp black 101, Printex 30, Printex U, Printex XE2,
      special black 4, and special black 6), spark discharge soot (GfG), and graphite
      powder was measured by a van der Pauw arrangement. Additionally the influence of
      inorganic admixtures on the conductivity of carbonaceous materials was proven to
      follow the percolation theory. Structural and oxidation characteristics obtained
      with Raman microspectroscopy and temperature programmed oxidation, respectively,
      were correlated with the electrical conductivity data. Moreover, a thermophoretic
      precipitator has been applied to deposit soot particles from the exhaust stream
      between interdigital electrodes. This combines a controlled and size independent
      particle collection method with the conductivity measurement principle. A test
      vehicle was equipped with the AVL Micro Soot Sensor (photoacoustic soot sensor)
      to prove the conductometric sensor principle with an independent and reliable
      technique. Our results demonstrate promising potential of the conductometric
      sensor for on-board particle diagnostic. Furthermore this sensor can be applied
      as a simple, rapid, and cheap analytical tool for characterization of soot
      structure.

PMID- 22455450
TI  - Trends and characteristics of injuries in the State of Qatar: hospital-based
      study.
AB  - Injuries account for a large burden of mortality and morbidity in the State of
      Qatar. No comprehensive study has been conducted on all types of injuries in the
      State of Qatar. The objective of this study was to determine the trend in the
      number, incidence and pattern of injuries in the State of Qatar. This hospital
      based study is a retrospective analysis of 53,366 patients treated at the
      accident and emergency and trauma centres for injuries during the period from
      2006 to 2010. Injuries were determined according to the ICD 10 criteria. The
      details of the entire trauma patients who were involved in occupational/domestic
      injuries were extracted from the database of the Emergency Medical Services
      (EMS), Hamad Medical Corporation. Our results demonstrated that the rates of
      injury remained relatively stable in the State of Qatar over the five-year
      period. Those most at risk of injury were non-Qatari males who were below 30
      years. Road traffic accidents (RTA) (36.7%) followed by falls causing back
      injuries (11.0%) were the most common types of injuries during the period. Most
      of the injuries occurred at the head for both males (17.7%) and females (13.5%);
      this was consistently the case across all of the age groups. The greatest
      proportion of RTA (21.2%), industrial machinery injuries (16.4%), construction
      injuries (15.5%), recreational sporting injuries (20.5%) and beach/sea/ocean
      injuries (15.0%) resulted in head injuries. Intervention efforts need to be aimed
      at reducing occupational injuries, RTA injuries and work-related hazards in the
      State of Qatar.

PMID- 22455451
TI  - Dual function of RGD-modified VEGI-192 for breast cancer treatment.
AB  - Identification of endogenous angiogenesis inhibitors has led to development of an
      increasingly attractive strategy for cancer therapy and other angiogenesis-driven
      diseases. Vascular endothelial growth inhibitor (VEGI), a potent and relatively
      nontoxic endogenous angiogenesis inhibitor, has been intensively studied, and
      this work shed new light on developing promising anti-angiogenic strategies. It
      is well-documented that the RGD (Arg-Gly-Asp) motif exhibits high binding
      affinity to integrin alpha(v)beta(3), which is abundantly expressed in cancer
      cells and specifically associated with angiogenesis on tumors. Here, we designed
      a fusion protein containing the special RGD-4C motif sequence and VEGI-192, aimed
      at offering more effective multiple targeting to tumor cells and tumor
      vasculature, and higher anti-angiogenic and antitumor efficacy. Functional tests
      demonstrated that the purified recombinant human RGD-VEGI-192 protein (rhRGD-VEGI
      192) potently inhibited endothelial growth in vitro and suppressed
      neovascularization in chicken chorioallantoic membrane in vivo, to a higher
      degree as compared with rhVEGI-192 protein. More importantly, rhRGD-VEGI-192, but
      not rhVEGI-192 protein, could potentially target MDA-MB-435 breast tumor cells,
      significantly inhibiting growth of MDA-MB-435 cells in vitro, triggered apoptosis
      in MDA-MB-435 cells by activation of caspase-8 as well as caspase-3, which was
      mediated by activating the JNK signaling associated with upregulation of pro
      apoptotic protein Puma, and consequently led to the observed significant
      antitumor effect in vivo against a human breast cancer xenograft. Our study
      indicated that the RGD-VEGI-192 fusion protein might represent a novel anti
      angiogenic and antitumor strategy.

PMID- 22455452
TI  - De novo synthesis of benzosceptrin C and nagelamide H from 7-15N-oroidin:
      implications for pyrrole-aminoimidazole alkaloid biosynthesis.
AB  - De novo synthesis of the natural products benzosceptrin C (7) and nagelamide H
      (8) was achieved using cell-free enzyme preparations from the marine sponges
      Agelas sceptrum and Stylissa caribica employing synthetic 7-(15)N-oroidin. These
      studies provide direct experimental evidence to support the long-standing, but
      untested, hypothesis that oroidin is a precursor to more complex pyrrole
      aminoimidazole alkaloids, such as the sceptrins, benzosceptrins, and nagelamides.
      In addition, a new nagelamide, didebromonagelamide A (5b), was isolated from S.
      caribica, representing the first report of a nagelamide-like compound from the
      Caribbean.

PMID- 22455453
TI  - Regioselective Cu(I)-catalyzed tandem A3-coupling/decarboxylative coupling to 3
      amino-1,4-enynes.
AB  - An efficient and novel copper-mediated protocol for the synthesis of 3-amino-1,4
      enynes from glyoxylic acid, an amine, and an alkyne was developed. This new
      reaction involving two sequential C-C bond formations is air and moisture
      tolerant and proceeds via a tandem A(3)-coupling and a selective decarboxylative
      coupling.

PMID- 22455455
TI  - Films of end-grafted hyaluronan are a prototype of a brush of a strongly charged,
      semiflexible polyelectrolyte with intrinsic excluded volume.
AB  - Hyaluronan (HA) is a naturally occurring linear, negatively charged
      polysaccharide that plays a vital role in the organization and function of
      pericellular coats and extracellular matrices in vertebrates, and that is
      becoming increasingly popular in biomedical applications. To gain insight into
      the physical phenomena that govern the mechanical behavior of HA assemblies, we
      have studied the response of films of end-grafted HA to compression over a large
      range of ionic strength. Compression forces were measured as a function of the
      absolute distance between a colloidal probe and the planar surface on which the
      HA film was constructed, using a combined atomic force microscopy and reflection
      interference contrast microscopy setup. The HA films were well-defined in the
      sense that they are made of chains with a narrow size distribution that are
      grafted at controlled density to a solid support. Detailed comparison of the
      experimental data with analytical expressions derived from polymer and
      polyelectrolyte brush theory reveals that films of end-grafted HA behave as
      strongly charged polyelectrolyte brushes. To quantitatively reproduce the
      experimental data, intrinsic excluded volume interactions and chain stiffness of
      the polymer backbone must be taken into account. At low ionic strength, chains
      become almost fully stretched. In our experimental system, several micrometer
      thick films are formed that reach a hydration of up to 99.98%, and the brush
      thickness decreases by more than 5-fold with increasing ionic strength. More
      generally, the study provides quantitative theoretical predictions for the film
      thickness and compressive response as a function of HA length, grafting density
      and ionic strength.

PMID- 22455454
TI  - A one-year prospective study of the safety, tolerability and pharmacokinetics of
      the highest available dose of paliperidone palmitate in patients with
      schizophrenia.
AB  - BACKGROUND: There are no previous reports of paliperidone palmitate's (PP) long
      term tolerability or pharmacokinetics of the highest dose in patients with
      schizophrenia. This study evaluates safety and tolerability, as well as
      pharmacokinetics, of the highest marketed dose of PP (150 mg eq. [234 mg]) in
      stable patients with schizophrenia over a 1-year period. METHODS: In this 1-year
      prospective study, eligible patients (aged 18-65 years; Positive and Negative
      Syndrome Scale's total score <= 70) received an initial deltoid injection of PP
      150 mg eq. The second injection one week later and subsequent once-monthly
      injections were deltoid or gluteal. All injections were to be PP 150 mg eq.
      Patients willing to participate in intensive pharmacokinetic sampling were
      classified as Treatment A. Patients unwilling to undergo intensive
      pharmacokinetic sampling or unable to tolerate the 150 mg eq. dose (consequently
      receiving flexible doses of 50, 100 or 150 mg eq.) were classified as Treatment
      B. RESULTS: Of the 212 patients (safety analysis set), 73% were men; 45% white;
      20% black; 34% Asians; mean (SD) age 41 (10.2) years, and mean (SD) baseline
      Positive and Negative Syndrome Scale total score 54.9 (9.03). A total of 53% (n =
      113) patients completed the study and 104 received PP 150 mg eq. throughout. Mean
      (SD) mode dose of PP was 144.8 (19.58) mg eq. The dosing initiation regimen
      resulted in rapidly achieved and maintained therapeutic paliperidone levels over
      the study (average concentrations during the dosing interval were 34.7, 40.0, and
      47.8 ng/mL after the 2nd, 8th, and 14th injection respectively). Most frequent
      (>= 10%) treatment-emergent adverse events were nasopharyngitis (n = 37),
      insomnia (n = 32), injection-site pain (n = 32), headache (n = 28), and
      tachycardia (n = 27). Akathisia (n = 19) and tremor (n = 11) were the most common
      extrapyramidal adverse events. 33 patients had an SAE and 27 discontinued due to
      treatment-emergent adverse events. No deaths were reported. Mean (SD) weight
      change from baseline was 2.5 (5.41) kg at endpoint. Patients' psychoses remained
      stable. CONCLUSIONS: Safety results after one-year therapy with the highest
      available dose of once-monthly paliperidone palmitate were consistent with
      results from previous studies, with no new concerns noted. Plasma concentrations
      were within the expected range. TRIAL REGISTRATION NO: ClinicalTrials.gov:
      NCT01150448.

PMID- 22455457
TI  - Massively parallel single-molecule and single-cell emulsion reverse transcription
      polymerase chain reaction using agarose droplet microfluidics.
AB  - A microfluidic device for performing single copy, emulsion Reverse Transcription
      Polymerase Chain Reaction (RT-PCR) within agarose droplets is presented. A two
      aqueous-inlet emulsion droplet generator was designed and fabricated to produce
      highly uniform monodisperse picoliter agarose emulsion droplets with RT-PCR
      reagents in carrier oil. Template RNA or cells were delivered from one inlet with
      RT-PCR reagents/cell lysis buffer delivered separately from the other. Efficient
      RNA/cell encapsulation and RT-PCR at the single copy level was achieved in
      agarose-in-oil droplets, which, after amplification, can be solidified into
      agarose beads for further analysis. A simple and efficient method to graft primer
      to the polymer matrix using 5'-acrydite primer was developed to ensure highly
      efficient trapping of RT-PCR products in agarose. High-throughput single RNA
      molecule/cell RT-PCR was demonstrated in stochastically diluted solutions. Our
      results indicate that single-molecule RT-PCR can be efficiently carried out in
      agarose matrix. Single-cell RT-PCR was successfully performed which showed a
      clear difference in gene expression level of EpCAM, a cancer biomarker gene, at
      the single-cell level between different types of cancer cells. This work clearly
      demonstrates for the first time, single-copy RT-PCR in agarose droplets. We
      believe this will open up new possibilities for viral RNA detection and single
      cell transcription analysis.

PMID- 22455456
TI  - Identification of microRNAs from Amur grape (Vitis amurensis Rupr.) by deep
      sequencing and analysis of microRNA variations with bioinformatics.
AB  - BACKGROUND: MicroRNA (miRNA) is a class of functional non-coding small RNA with
      19-25 nucleotides in length while Amur grape (Vitis amurensis Rupr.) is an
      important wild fruit crop with the strongest cold resistance among the Vitis
      species, is used as an excellent breeding parent for grapevine, and has elicited
      growing interest in wine production. To date, there is a relatively large number
      of grapevine miRNAs (vv-miRNAs) from cultivated grapevine varieties such as Vitis
      vinifera L. and hybrids of V. vinifera and V. labrusca, but there is no report on
      miRNAs from Vitis amurensis Rupr, a wild grapevine species. RESULTS: A small RNA
      library from Amur grape was constructed and Solexa technology used to perform
      deep sequencing of the library followed by subsequent bioinformatics analysis to
      identify new miRNAs. In total, 126 conserved miRNAs belonging to 27 miRNA
      families were identified, and 34 known but non-conserved miRNAs were also found.
      Significantly, 72 new potential Amur grape-specific miRNAs were discovered. The
      sequences of these new potential va-miRNAs were further validated through miR
      RACE, and accumulation of 18 new va-miRNAs in seven tissues of grapevines
      confirmed by real time RT-PCR (qRT-PCR) analysis. The expression levels of va
      miRNAs in flowers and berries were found to be basically consistent in identity
      to those from deep sequenced sRNAs libraries of combined corresponding tissues.
      We also describe the conservation and variation of va-miRNAs using miR-SNPs and
      miR-LDs during plant evolution based on comparison of orthologous sequences, and
      further reveal that the number and sites of miR-SNP in diverse miRNA families
      exhibit distinct divergence. Finally, 346 target genes for the new miRNAs were
      predicted and they include a number of Amur grape stress tolerance genes and many
      genes regulating anthocyanin synthesis and sugar metabolism. CONCLUSIONS: Deep
      sequencing of short RNAs from Amur grape flowers and berries identified 72 new
      potential miRNAs and 34 known but non-conserved miRNAs, indicating that specific
      miRNAs exist in Amur grape. These results show that a number of regulatory miRNAs
      exist in Amur grape and play an important role in Amur grape growth, development,
      and response to abiotic or biotic stress.

PMID- 22455458
TI  - Working with immigrant families raising a child with a disability: challenges and
      recommendations for healthcare and community service providers.
AB  - PURPOSE: Although providing culturally sensitive care is an important element of
      family-centered rehabilitation very is little known about providers' experiences
      working with immigrant families in pediatric settings. The purpose of this study
      is to develop a better understanding of the experiences of service providers
      working with immigrant families raising a child with a physical disability.
      METHOD: We draw on a qualitative approach involving in-depth interviews and focus
      groups with healthcare and community service providers (n = 13) in two multi
      cultural Canadian cities. RESULTS: The findings indicate that healthcare and
      community service providers encounter several challenges in providing care to
      immigrant families raising a child with a disability. Such challenges include the
      following: (1) lack of training in providing culturally sensitive care; (2)
      language and communication issues; (3) discrepancies in conceptualizations of
      disability between healthcare providers and immigrant parents; (4) building
      rapport; and (5) helping parents to advocate for themselves and their children.
      Service providers also have several recommendations for improving services to
      better meet the needs of immigrant families. CONCLUSION: Clinicians should be
      cognizant of how culture influences the care they provide to clients. More
      training opportunities are needed for enhancing culturally sensitive care.
      IMPLICATIONS FOR REHABILITATION: * Pediatric rehabilitation providers working
      with immigrant families raising a child with a disability should engage in
      training and education around culturally sensitive care to better meet the needs
      of these clients. * More time is needed when working with immigrant families to
      build trust and rapport. * Clinicians need to be sensitive around gender issues
      and try to involve both parents in the decision making around the care for their
      child. * Healthcare providers should help clients to become more aware of the
      resources available to them in the hospital and in the community.

PMID- 22455459
TI  - K3[Tb(x)Eu(1-x)Ge3O8(OH)2] (x = 1, 0.88, 0.67, 0): 2D-layered lanthanide
      germanates with tunable photoluminescent properties.
AB  - A family of novel 2D-layered lanthanide germanates K(3)[Tb(x)Eu(1
      x)Ge(3)O(8)(OH)(2)] (x = 1, 0.88, 0.67, 0; denoted as TbGeO-JU-87,
      Tb(0.88)Eu(0.12)GeO-JU-87, Tb(0.67)Eu(0.33)GeO-JU-87, and EuGeO-JU-87) were
      synthesized under mild hydrothermal conditions in a concentrated gel system. They
      are isostructural, as confirmed by the powder X-ray diffraction analysis. The
      single-crystal X-ray diffraction analysis of EuGeO-JU-87 reveals that it is a 2D
      layered [EuGe(3)O(8)(OH)(2)](n)(3n-) anionic framework, which is built up from
      GeO(4)H/GeO(4) tetrahedra and EuO(6) octahedra by sharing vertex O atoms. Charge
      neutrality is achieved by K(+) ions located in the free void space.
      Interestingly, photoluminescence studies show that Tb(0.88)Eu(0.12)GeO-JU-87 and
      Tb(0.67)Eu(0.33)GeO-JU-87 exhibit a high Tb(3+)-to-Eu(3+) energy-transfer
      efficiency and the Tb(x)Eu(1-x)GeO-JU-87 system displays tunable photoluminescent
      properties.

PMID- 22455460
TI  - Long-term management of scalp psoriasis: perspectives from the International
      Psoriasis Council.
AB  - The scalp is a well-known predilection site for psoriasis. Epidemiological data
      on the various manifestations of scalp psoriasis as well as on its therapeutic
      management are sparse. The understanding of the natural course of scalp psoriasis
      is relevant for its therapeutic management. In over 25% of patients, scalp
      psoriasis is the first signal of the psoriatic condition. Nevertheless, few of
      the therapies currently used for the treatment of scalp psoriasis have been
      evaluated for efficacy in the setting of well-designed, well-controlled clinical
      studies. The lack of comparative data impedes the interpretation of the results
      from studies of scalp psoriasis. Long-term studies of the efficacy and safety of
      scalp treatments are lacking. Moreover, clinical studies generally do not
      incorporate quality of life impact or mechanisms to enhance adherence thus
      hindering the optimal management of the patient over the long-term. Consequently,
      this report will evaluate the available data and the associated factors to be
      considered in the development of a treatment paradigm for the long-term
      management of the scalp psoriasis patient.

PMID- 22455461
TI  - Cardiovascular magnetic resonance of myocardial edema using a short inversion
      time inversion recovery (STIR) black-blood technique: diagnostic accuracy of
      visual and semi-quantitative assessment.
AB  - BACKGROUND: The short inversion time inversion recovery (STIR) black-blood
      technique has been used to visualize myocardial edema, and thus to differentiate
      acute from chronic myocardial lesions. However, some cardiovascular magnetic
      resonance (CMR) groups have reported variable image quality, and hence the
      diagnostic value of STIR in routine clinical practice has been put into question.
      The aim of our study was to analyze image quality and diagnostic performance of
      STIR using a set of pulse sequence parameters dedicated to edema detection, and
      to discuss possible factors that influence image quality. We hypothesized that
      STIR imaging is an accurate and robust way of detecting myocardial edema in non
      selected patients with acute myocardial infarction. METHODS: Forty-six
      consecutive patients with acute myocardial infarction underwent CMR (day 4.5, +/-
      1.6) including STIR for the assessment of myocardial edema and late gadolinium
      enhancement (LGE) for quantification of myocardial necrosis. Thirty of these
      patients underwent a follow-up CMR at approximately six months (195 +/- 39 days).
      Both STIR and LGE images were evaluated separately on a segmental basis for image
      quality as well as for presence and extent of myocardial hyper-intensity, with
      both visual and semi-quantitative (threshold-based) analysis. LGE was used as a
      reference standard for localization and extent of myocardial necrosis (acute) or
      scar (chronic). RESULTS: Image quality of STIR images was rated as diagnostic in
      99.5% of cases. At the acute stage, the sensitivity and specificity of STIR to
      detect infarcted segments on visual assessment was 95% and 78% respectively, and
      on semi-quantitative assessment was 99% and 83%, respectively. STIR
      differentiated acutely from chronically infarcted segments with a sensitivity of
      95% by both methods and with a specificity of 99% by visual assessment and 97% by
      semi-quantitative assessment. The extent of hyper-intense areas on acute STIR
      images was 85% larger than those on LGE images, with a larger myocardial salvage
      index in reperfused than in non-reperfused infarcts (p = 0.035). CONCLUSIONS:
      STIR with appropriate pulse sequence settings is accurate in detecting acute
      myocardial infarction (MI) and distinguishing acute from chronic MI with both
      visual and semi-quantitative analysis. Due to its unique technical
      characteristics, STIR should be regarded as an edema-weighted rather than a
      purely T2-weighted technique.

PMID- 22455462
TI  - Autoinduction of phase I and phase II metabolism of artemisinin in rats.
AB  - This study was designed to get the direct evidence of the autoinduction
      metabolism for the antimalarial drug artemisinin (QHS). The sex effect on the
      pharmacokinetic profiles of QHS and its metabolites was also studied. Two groups
      of rats received a single oral dose of QHS, and another two groups of rats were
      given oral doses of QHS once daily for 5 consecutive days. Plasma samples and its
      phase I and phase II metabolites were analysed for QHS, using a validated liquid
      chromatography tandem mass spectrometric (LC-MS) method. Eight phase I
      metabolites (DQHS, M1-M7) and five phase II metabolites (M8-M12) of QHS were
      detected in rat plasma. The AUC(0-t) of the parent drug QHS, and its phase I
      metabolites DQHS, M2, M3 and M6 decreased significantly (p < 0.05) with increased
      oral clearance (CL/F) (p < 0.05) after 5-day oral doses of QHS to rats. There was
      no change (p > 0.05) in AUC of M1 and M4, whereas its metabolites M5 and M7
      exhibited higher AUC (p < 0.05). The AUC of phase II metabolites M8, M11 and M12
      also increased after multiple oral doses of QHS. Sex difference was observed for
      QHS and its metabolites DQHS, M1, M3, M5, M8 and M9 in rats after a single oral
      dose of QHS. The results gave the direct evidence for the autoinduction of both
      phase I and phase II metabolism of QHS. The sex effect existed for QHS.

PMID- 22455463
TI  - clusterProfiler: an R package for comparing biological themes among gene
      clusters.
AB  - Increasing quantitative data generated from transcriptomics and proteomics
      require integrative strategies for analysis. Here, we present an R package,
      clusterProfiler that automates the process of biological-term classification and
      the enrichment analysis of gene clusters. The analysis module and visualization
      module were combined into a reusable workflow. Currently, clusterProfiler
      supports three species, including humans, mice, and yeast. Methods provided in
      this package can be easily extended to other species and ontologies. The
      clusterProfiler package is released under Artistic-2.0 License within
      Bioconductor project. The source code and vignette are freely available at
      http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.

PMID- 22455464
TI  - Interaction between physical activity and sleep duration in relation to insulin
      resistance among non-diabetic Chinese adults.
AB  - BACKGROUND: It is of a public health interest to explore the relationship between
      different types of physical activity, sleep duration and diabetes/insulin
      resistance. However, little is known about such relationship. This study examines
      the single and joint associations of different types of physical activity, and
      sleep duration on insulin resistance among non-diabetic Chinese adults. METHODS:
      Data was collected from 1124 non-diabetic adults in Jiangsu Province from the
      China Health and Nutrition Survey (CHNS). Domestic, occupational, transportation
      and leisure physical activity were assessed in terms of metabolic equivalent
      (MET)-hours-per-week to account for both intensity and time spent. Sleep duration
      was categorized into three groups: <= 7 hours, 7-9 hours, and >= 9 hours. Insulin
      resistance was evaluated by the homeostasis model of assessment (HOMA) and
      defined as the highest quartile of HOMA. RESULTS: Total physical activity was
      mainly composed of occupational activity (75.1%), followed orderly by domestic,
      transportation and leisure time activity in both men and women. Total physical
      activity level was strongly negatively associated with fasting insulin and HOMA
      (p < 0.001). Among four types of physical activity, occupational activity was
      significantly negatively associated with HOMA after full adjustment (p < 0.05).
      Transportation activity was also negatively associated with HOMA when adjusted
      for age and gender (p = 0.028). Moreover, the combination of low physical
      activity and short sleep duration was associated with the highest odds of insulin
      resistance (adjusted OR = 3.26, 95% CI: 1.57-6.78), compared to those with high
      physical activity and adequate sleep duration. CONCLUSIONS: Physical activity,
      mainly occupational physical activity, was negatively associated with insulin
      resistance in non-diabetic Chinese population, independently of potential
      confounders. There was a synergic effect of low physical activity and short sleep
      duration on insulin resistance.

PMID- 22455465
TI  - Facile synthesis of azaspirocycles via iron trichloride-promoted
      cyclization/chlorination of cyclic 8-aryl-5-aza-5-tosyl-2-en-7-yn-1-ols.
AB  - A simple and efficient FeCl(3)-promoted cyclization/chlorination of cyclic
      tosylamine-tethered 8-aryl-2-en-7-yn-1-ols was observed. The reaction proceeded
      instantaneously at 23  degrees C in air to afford (Z)-4-(arylchloromethylene)
      substituted azaspirocycles in good to excellent yields. This transformation can
      also be applied to the synthesis of spirocarbocyclic analogues from cyclic 8-aryl
      2-en-7-yn-1-ols and FeCl(3).

PMID- 22455466
TI  - Electron paramagnetic resonance spectroscopic evidence for the interaction of
      HAlOH with water molecules.
AB  - The complex HAlOH:(H(2)O) has been detected by matrix-isolation IR spectroscopy.
      This complex was speculated to be the species responsible for the
      chemiluminescent glow associated with the explosion of trimethyl aluminum or
      aluminum grenades in the upper atomosphere. Theoretical studies suggest that
      HAlOH:(H(2)O)(n) is a critical precursor in the formation of H(2) in the reaction
      of Al with liquid water. In our study, Al atoms were reacted with mixtures of
      D(2)O/He or H(2)(17)O/He in an adamantane matrix in a metal-atom reactor, known
      as a rotating cryostat, maintained at 77 K and at <10(-6) Torr. In addition to
      DAlOD and HAlOH, which formed from the reaction of Al atoms with adventitious
      water, EPR analysis of the Al-D(2)O/He reaction mixture from 77 to 290 K showed
      that HAlOH:(D(2)O) and DAlOD:(D(2)O) formed. The experimental nuclear hyperfine
      interactions (hfis) for these species were in close agreement with those
      calculated using the B3LYP density functional method and the 6-311+G(2df,p) basis
      set. The effect of complexation is to lower the Al hfi of HAlOH and DAlOD by ca.
      8%, the H hfi of HAlOH by ca. 28%, and the D hfi of DAlOD by ca. 35%.

PMID- 22455467
TI  - Ligand-decorated nanogels: fast one-pot synthesis and cellular targeting.
AB  - Nanoscale vehicles for delivery have been of interest and extensively studied for
      two decades. However, the encapsulation stability of hydrophobic drug molecules
      in delivery vehicles and selective targeting these vehicles into disease cells
      are potential hurdles for efficient delivery systems. Here we demonstrate a
      simple and fast synthetic protocol of nanogels that shows high encapsulation
      stabilities. These nanogels can also be modified with various targeting ligands
      for active targeting. We show that the targeting nanogels (T-NGs), which are
      prepared within 2 h by a one-pot synthesis, exhibit very narrow size
      distributions and have the versatility of surface modification with cysteine
      modified ligands including folic acid, cyclic arginine-glycine-aspartic acid
      (cRGD) peptide, and cell-penetrating peptide. T-NGs hold their payloads, undergo
      facilitated cell internalization by receptor-mediated uptake, and release their
      drug content inside cells due to the reducing intracellular environment.
      Selective cytotoxicity to cells, which have complementary receptors, is also
      demonstrated.

PMID- 22455468
TI  - Epigenetic features are significantly associated with alternative splicing.
AB  - BACKGROUND: While alternative splicing (AS) contributes greatly to protein
      diversities, the relationship between various types of AS and epigenetic factors
      remains largely unknown. RESULTS: In this study, we discover that a number of
      epigenetic features, including DNA methylation, nucleosome occupancy, specific
      histone modifications and protein features, are strongly associated with AS. To
      further enhance our understanding of the association between these features and
      AS, we cluster our investigated features based on their association patterns with
      each AS type into four groups, with H3K36me3, EGR1, GABP, SRF, SIN3A and RNA Pol
      II grouped together and showing strongest association with AS. In addition, we
      find that the AS types can be classified into two general classes, namely the
      exon skipping related process (ESRP), and the alternative splice site selection
      process (ASSP), based on their association levels with the epigenetic features.
      CONCLUSION: Our analysis thus suggests that epigenetic features are likely to
      play important roles in regulating AS.

PMID- 22455469
TI  - Reliability of the Fox-walk test in patients with rheumatoid arthritis.
AB  - PURPOSE: The Fox-walk test is a new method used to estimate aerobic capacity
      outside a clinical environment, which may be useful in the implementation of
      daily health-enhancing physical activity. The aim of our study was to investigate
      the reliability of the test in people with rheumatoid arthritis (RA). METHOD:
      Fifteen participants performed the Fox-walk test three times with weekly
      intervals. The intraclass correlation coefficient (ICC), the standard error of
      measurement (SEM) and the smallest detectable change (SDC) were used to estimate
      the reliability. General health perception, lower limb pain and fatigue were
      measured to determine their potential influence on the reliability. RESULTS:
      There were no systematic differences between the three test occasions (p = 0.190)
      and the reliability was almost perfect (ICC = 0.982). None of the covariates
      influenced the reliability. The SEM was 0.999 ml/kg/min or 3.4% and the SDC was
      2.769 ml/kg/min or 9.4%. CONCLUSIONS: These findings demonstrate that the Fox
      walk test is reliable in people with RA and enables differentiation between
      people with RA and monitoring progress. The validity of the test among people
      with RA is still to be determined. IMPLICATIONS FOR REHABILITATION: * The Fox
      walk test is a new method to estimate aerobic capacity and could be performed
      walking or running. * The test is self administered without expensive equipment
      and is available in 150 public places in Sweden and several other European
      countries. * The Fox-walk test is a reliable test for use among people with
      rheumatoid arthritis monitoring the progress of their physical activity.

PMID- 22455470
TI  - Molybdenum 1,4-diazabuta-1,3-diene tricarbonyl solvento complexes revisited: from
      solvatochromism to attractive ligand-ligand interaction.
AB  - Various complexes of the types [Mo(DAD)(CO)(3)L] (L = CO, MeCN, MeOH, THF, DMSO,
      DMF, Me(2)CO, EtOAc, THT, Im(H), Im(1), tBuNC, nBu(3)P), (ER(4))[Mo(DAD)(CO)(3)X]
      (ER(4) = NEt(4)(+); X(-) = Cl(-), Br(-), I(-), NCS(-), CN(-) and ER(4)(+) =
      PPh(4)(+); X(-) = N(3)(-)), and (ER(4))[{Mo(DAD)(CO)(3)}(2)(MU-X)] (ER(4)(+) =
      NEt(4)(+); X(-) = CN(-), OAc(-) and ER(4)(+) = PPh(4)(+); X(-) = N(3)(-); DAD =
      N,N'-bis(2,6-dimethylphenyl)butane-2,3-diimine) were prepared by ligand exchange
      from cycloheptatriene molybdenum tricarbonyl. A total of 19 crystal structures
      were determined, including unprecedented structural characterization of
      molybdenum(0) coordination by dimethyl sulfoxide (DMSO), methanol, ethyl acetate
      (EtOAc), acetone, and N,N-dimethylformamide (DMF). Correlation of (13)C NMR
      shifts with the complex geometry suggests a direct ligand-ligand interaction
      between DAD and O-bonded coligands with C?O and S?O double bonds, such as EtOAc,
      Me(2)CO, DMF, and DMSO. Unexpectedly, the solvatochromic properties of these
      tricarbonyl complexes [Mo(DAD)(CO)(3)L] are unfavorable for the determination of
      Kamlet-Taft parameters of the corresponding solvent L. Contrastingly, the UV/vis
      absorption of [Mo(DAD)(CO)(4)] is strongly correlated with the Kamlet-Taft
      parameter pi*, which is shown for 22 solvents, including seven room temperature
      ionic liquids.

PMID- 22455471
TI  - Positron lifetime reveals the nano level packing in complex polysaccharide-rich
      hydrolysate matrixes.
AB  - Positron annihilation lifetime spectroscopy (PALS) was used to quantify the free
      volume and molecular packing in hydrolysate and hemicellulose-based barriers
      films, derived from process streams during wood processing operations. These
      hydrolysate films, comprising a fair share of lignin coexisting with poly- and
      oligo-saccharides, have very low but variable oxygen permeability but differ
      among themselves with respect to barrier performance as well as molecular weight,
      degree of branching, and monosaccharide residue main chain composition. From PALS
      measurements on hydrolysates, the free volume hole radius (r(h)), radius
      distributions (n(r(h))), volume-weighted hole sizes (<v(h)>(v)), and hole volume
      distributions (g(v(h))) were calculated showing that the hydrolysate matrixes are
      very densely packed with small holes. The results show a clear relationship
      between hydrolysate molecular architecture and composition, the nanolevel
      molecular packing, and the ability of suppressing the diffusion of oxygen through
      the film.

PMID- 22455472
TI  - Good practice in mental health care for socially marginalised groups in Europe: a
      qualitative study of expert views in 14 countries.
AB  - BACKGROUND: Socially marginalised groups tend to have higher rates of mental
      disorders than the general population and can be difficult to engage in health
      care. Providing mental health care for these groups represents a particular
      challenge, and evidence on good practice is required. This study explored the
      experiences and views of experts in 14 European countries regarding mental health
      care for six socially marginalised groups: long-term unemployed; street sex
      workers; homeless; refugees/asylum seekers; irregular migrants and members of the
      travelling communities. METHODS: Two highly deprived areas were selected in the
      capital cities of 14 countries, and experts were interviewed for each of the six
      marginalised groups. Semi-structured interviews with case vignettes were
      conducted to explore experiences of good practice and analysed using thematic
      analysis. RESULTS: In a total of 154 interviews, four components of good practice
      were identified across all six groups: a) establishing outreach programmes to
      identify and engage with individuals with mental disorders; b) facilitating
      access to services that provide different aspects of health care, including
      mental health care, and thus reducing the need for further referrals; c)
      strengthening the collaboration and co-ordination between different services; and
      d) disseminating information on services both to marginalised groups and to
      practitioners in the area. CONCLUSIONS: Experts across Europe hold similar views
      on what constitutes good practice in mental health care for marginalised groups.
      Care may be improved through better service organisation, coordination and
      information.

PMID- 22455473
TI  - Oxazolidinone-promoted, torquoselective Nazarov cyclizations.
AB  - Oxazolidinones are powerful promoters of the Nazarov reaction, enabling the
      cyclization of conventionally resistant substrates to be achieved under mild
      conditions. They exert excellent regio- and torquoselective control in both the
      conventional Nazarov reaction giving cyclopentenones and in the "interrupted"
      Nazarov reaction, giving more highly substituted multistereocenter containing
      products.

PMID- 22455476
TI  - Theoretical insights into the aggregation-induced emission by hydrogen bonding: a
      QM/MM study.
AB  - We investigate the excited-state decay processes for the 3-(2-cyano-2-
      phenylethenyl-Z)-NH-indole (CPEI) in the solid phase through combined quantum
      mechanics and molecular mechanics (QM/MM) and vibration correlation formalisms
      for radiative and nonradiative decay rates, coupled with time-dependent density
      functional theory (TDDFT). By comparing the isolated CPEI molecule and the
      molecule-in-cluster, we show that the molecular packing through intermolecular
      hydrogen-bonding interactions can hinder the excited-state nonradiative decay and
      thus enhance the fluorescence efficiency in the solid phase. Aggregation effect
      is shown to block the nonradiative decay process through hindering the low
      frequency vibration motions. The fluorescence quantum yields for both isolated
      molecule and aggregation are predicted to be insensitive to temperature due to
      the hydrogen-bonding nature, and their values at room temperature are consistent
      with the experiment.

PMID- 22455477
TI  - Hybrid CO2-philic surfactants with low fluorine content.
AB  - The relationships between molecular architecture, aggregation, and interfacial
      activity of a new class of CO(2)-philic hybrid surfactants are investigated. The
      new hybrid surfactant CF2/AOT4 [sodium (4H,4H,5H,5H,5H-pentafluoropentyl-3,5,5
      trimethyl-1-hexyl)-2-sulfosuccinate] was synthesized, having one hydrocarbon
      chain and one separate fluorocarbon chain. This hybrid H-F chain structure
      strikes a fine balance of properties, on one hand minimizing the fluorine
      content, while on the other maintaining a sufficient level of CO(2)-philicity.
      The surfactant has been investigated by a range of techniques including high
      pressure phase behavior, UV-visible spectroscopy, small-angle neutron scattering
      (SANS), and air-water (a/w) surface tension measurements. The results advance the
      understanding of structure-function relationships for generating CO(2)-philic
      surfactants and are therefore beneficial for expanding applications of CO(2) to
      realize its potential using the most economic and efficient surfactants.

PMID- 22455478
TI  - BACE1 dependent neuregulin processing: review.
AB  - Neuregulin-1 (NRG1), known also as heregulin, acetylcholine receptor inducing
      activity (ARIA), glial growth factor (GGF), or sensory and motor neuron derived
      factor (SMDF), plays essential roles in several developmental processes, and is
      required also later in life. Many variants of NRG1 are produced via alternative
      splicing and usage of distinct promoters. All contain an epidermal growth factor
      (EGF)-like domain, which alone is sufficient to bind and activate the cognate
      receptors, members of the ErbB family. NRG1 mediated signaling is crucial for
      cardiogenesis and the development of the mammary gland and ErbB2 (HER2), an
      orphan co-receptor for NRG1 is the target of the drug Herceptin? (trastuzumab)
      used for treatment of metastatic breast cancer. In the nervous system, NRG1
      controls the early development of subpopulations of neural crest cells. In
      particular, NRG1 acts as an essential paracrine signaling molecule expressed on
      the axonal surface, where it signals to Schwann cells throughout development and
      regulates the thickness of the myelin sheath. NRG1 is required also by other cell
      types in the nervous system, for instance as an axonal signal released by
      proprioceptive afferents to induce development of the muscle spindle, and it
      controls aspects of cortical interneuron development as well as the formation of
      thalamocortical projections. Work from several laboratories implicates
      dysregulation of NRG1/ErbB4 signaling in the etiology of schizophrenia.
      Biochemical studies have shown that the precursor proteins of NRG1 can be
      released from the membrane through limited proteolysis. In addition, most NRG1
      isoforms contain a transmembrane domain, which is processed by gamma-secretase
      after shedding. Thereby the intracellular domain is released into the cytoplasm.
      Despite this, the importance of NRG1 cleavage for its functions in vivo remained
      unclear until recently. beta- Secretase (beta-site amyloid precursor protein
      cleaving enzyme 1, BACE1) was first identified through its function as the rate
      limiting enzyme of amyloid-beta-peptide (Abeta) production. Abeta is the major
      component of amyloid plaques in Alzheimer's disease (AD). More recently it was
      shown that Neuregulin-1 is a major physiological substrate of BACE1 during early
      postnatal development. Mutant mice lacking BACE1 display severe hypomyelination
      of peripheral nerves similar to that seen in mice lacking NRG1/ErbB signaling in
      Schwann cells, and a BACE1-dependent activation of NRG1 in the process of
      peripheral myelination was proposed. Here we summarize the current knowledge
      about the role of NRG1 proteolysis for ErbB receptor mediated signaling during
      development and in Alzheimer's disease.

PMID- 22455479
TI  - Voltage-dependent Na+ channels as targets of BACE1 - implications for neuronal
      firing and beyond.
AB  - Voltage-dependent sodium channel complexes consist of a pore-forming and voltage
      sensing alpha-subunit and one or two beta-subunits. The latter are type I
      transmembrane proteins with a broad spectrum of functions in channel expression
      and surface targeting, in channel electrophysiology and, notably, in cell
      adhesion of excitable and non-excitable cells. Like the amyloid-precursor protein
      (APP), beta-subunits are substrates for sequential cleavage either by alpha- and
      gamma-secretase, or by beta- and gamma-secretase. Here, we focus on the
      processing of beta-subunits by the amyloidogenic beta-secretase, BACE1, which is
      up-regulated in Alzheimer's disease and is considered a highly promising
      pharmacologic target. Based on data from BACE1-deficient or over-expressing mice
      and from heterologous expression systems, this review summarizes our growing
      understanding of how BACE1-mediated cleavage of beta-subunits interferes with
      their multiple physiological functions.

PMID- 22455480
TI  - Three-dimensional heterostructure of metallic nanoparticles and carbon nanotubes
      as potential nanofiller.
AB  - The effect of the dimensionality of metallic nanoparticle-and carbon nanotube
      based fillers on the mechanical properties of an acrylonitrile butadiene styrene
      (ABS) polymer matrix was examined. ABS composite films, reinforced with low
      dimensional metallic nanoparticles (MNPs, 0-D) and carbon nanotubes (CNTs, 1-D)
      as nanofillers, were fabricated by a combination of wet phase inversion and hot
      pressing. The tensile strength and elongation of the ABS composite were increased
      by 39% and 6%, respectively, by adding a mixture of MNPs and CNTs with a total
      concentration of 2 wt%. However, the tensile strength and elongation of the ABS
      composite were found to be significantly increased by 62% and 55%, respectively,
      upon addition of 3-D heterostructures with a total concentration of 2 wt%. The 3
      D heterostructures were composed of multiple CNTs grown radially on the surface
      of MNP cores, resembling a sea urchin. The mechanical properties of the ABS/3-D
      heterostructured nanofiller composite films were much improved compared to those
      of an ABS/mixture of 0-D and 1-D nanofillers composite films at various filler
      concentrations. This suggests that the 3-D heterostructure of the MNPs and CNTs
      plays a key role as a strong reinforcing agent in supporting the polymer matrix
      and simultaneously serves as a discrete force-transfer medium to transfer the
      loaded tension throughout the polymer matrix.

PMID- 22455481
TI  - Engineering a polymeric gene delivery vector based on poly(ethylenimine) and
      hyaluronic acid.
AB  - In this work, the effects of primary amines, ligand targeting, and overall charge
      on the effectiveness of branched poly(ethylenimine)-hyaluronic acid conjugate
      (bPEI-HA) zwitterionic gene delivery vectors are investigated. To elucidate the
      relative importance of each of these parameters, we explored the zeta potential,
      cytotoxicity, and transfection efficiency for a variety of formulations of bPEI
      HA. It was found that the length of the hyaluronic acid (HA) oligosaccharide had
      the most significant effect on cytotoxicity and transfection efficiency with
      human mesenchymal stem cells. Test groups of bPEI incorporating HA with a length
      of 10 saccharides had significantly higher transfection efficiency (14.6 +/-
      2.0%) and lower cytotoxicity than other formulations tested, with the
      cytotoxicity of the group containing the greatest mass of 10 saccharide showing
      similar results as the positive controls at the highest polymer concentration
      (100 MUg/mL). Additionally, molar incorporation of HA, as opposed to the
      saccharide length and HA mass incorporation, had the greatest effect on zeta
      potential but a minor effect on both cytotoxicity and transfection efficiency.
      This work demonstrates the relative importance of each of these tunable design
      criteria when creating a zwitterionic polymeric gene delivery vector and provides
      useful specific information regarding the design of bPEI-HA gene delivery
      vectors.

PMID- 22455483
TI  - Should we perform noninvasive ventilation anywhere?

PMID- 22455484
TI  - IL-17 in chronic obstructive pulmonary disease.

PMID- 22455482
TI  - Pharmacist provision of primary health care: a modified Delphi validation of
      pharmacists' competencies.
AB  - BACKGROUND: Pharmacists have expanded their roles and responsibilities as a
      result of primary health care reform. There is currently no consensus on the core
      competencies for pharmacists working in these evolving practices. The aim of this
      study was to develop and validate competencies for pharmacists' effective
      performance in these roles, and in so doing, document the perceived contribution
      of pharmacists providing collaborative primary health care services. METHODS:
      Using a modified Delphi process including assessing perception of the frequency
      and criticality of performing tasks, we validated competencies important to
      primary health care pharmacists practising across Canada. RESULTS: Ten key
      informants contributed to competency drafting; thirty-three expert pharmacists
      replied to a second round survey. The final primary health care pharmacist
      competencies consisted of 34 elements and 153 sub-elements organized in seven
      CanMeds-based domains. Highest importance rankings were allocated to the domains
      of care provider and professional, followed by communicator and collaborator,
      with the lower importance rankings relatively equally distributed across the
      manager, advocate and scholar domains. CONCLUSIONS: Expert pharmacists working in
      primary health care estimated their most important responsibilities to be related
      to direct patient care. Competencies that underlie and are required for
      successful fulfillment of these patient care responsibilities, such as those
      related to communication, collaboration and professionalism were also highly
      ranked. These ranked competencies can be used to help pharmacists understand
      their potential roles in these evolving practices, to help other health care
      professionals learn about pharmacists' contributions to primary health care, to
      establish standards and performance indicators, and to prioritize supports and
      education to maximize effectiveness in this role.

PMID- 22455486
TI  - Optical techniques in pulmonary medicine. SPIE photonics West.
AB  - There is ongoing interest in the emerging field of pulmonary photonic-based
      diagnostics. Potential clinical need areas that are being actively investigated
      at this time include airway and peripheral lung cancer diagnostics, pulmonary
      parenchymal and interstitial disorders, alveolar structure function, inhalation
      injury, ciliary function analysis, asthma and obstructive lung diseases.

PMID- 22455487
TI  - Unifying thoracic biomarkers: surfactant protein-D and beyond.
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive disorder that
      affects 300 million people worldwide and is responsible for 3 million deaths
      annually. Currently, there are no accepted biomarkers of COPD, which has impaired
      drug development and management of patients with COPD. Pneumoproteins, which are
      proteins synthesized predominantly in the lungs, are promising blood biomarkers
      because they have high specificity for lung disease. The most promising is
      surfactant protein-D, which is synthesized largely in Type 2 pneumocytes, and its
      blood concentrations have been associated with COPD and with certain clinical end
      points such as mortality. In this paper, we discuss surfactant protein-D and
      other pneumoproteins as promising biomarkers of COPD.

PMID- 22455488
TI  - Fluid administration limited by lung sonography: the place of lung ultrasound in
      assessment of acute circulatory failure (the FALLS-protocol).
AB  - The FALLS-protocol is included in a limited investigation to diagnose the cause
      of shock. After simple echocardiography has ruled out obstructive shock
      (tamponade, pulmonary embolism), the lung is investigated. Absence of
      disseminated lung rockets rules out cardiogenic shock. At this point, hypovolemic
      and septic shock are differential diagnoses (rarities apart), and the FALLS
      protocol provides fluid therapy with constant monitoring of lung artifacts.
      Hypovolemic shock will eventually improve - septic shock will not, and the slight
      excess fluid creates an early, silent stage of interstitial edema, demonstrated
      by B-lines, demanding interruption of fluid therapy. This sequential approach,
      combined with the usual, clinical, biochemical and echocardiographic parameters,
      must be evaluated in multicenter studies.

PMID- 22455489
TI  - Disparities in subgroup populations enrolled in lung cancer trials.
AB  - Lung cancer is the leading cause of cancer-related mortality worldwide. All drugs
      available for the treatment of lung cancer reached the market after reporting
      positive results from pivotal clinical studies. However, in these trials not all
      patient subgroups are adequately represented, with some discrepancies reported in
      patients' accrual especially concerning age, gender and ethnicity. Hence, a new
      drug entering the market for the treatment of all patients may have been
      investigated only in certain patient subgroups, while the reported results have
      been generalized for the therapy of all patients. The impact of certain
      characteristics such as gender, ethnicity and age of patients enrolled in
      randomized trials on the final results has been examined and discussed in this
      article.

PMID- 22455490
TI  - IL-17 in human asthma.
AB  - Asthma is perceived as a heterogeneous disease with several clinical phenotypes
      and triggering factors. In general, cytokines from T-helper 2 cells are believed
      to be critical contributors of asthma. In recent years, IL-17, another T-helper
      lymphocyte-associated cytokine, has been put forward as another potentially
      important mediator of asthma. Currently, several drugs that target IL-17
      signaling are being tested in clinical trials. With the aim to find whether there
      are any specific features of this heterogeneous disease that potentially could be
      relieved by the use of IL-17-targeting drugs, this review scrutinizes the
      evidence for an involvement of IL-17 in human asthma.

PMID- 22455491
TI  - Respiratory health in women: from menarche to menopause.
AB  - Gender differences in respiratory health have, in recent years, been the focus of
      considerable scientific effort. This paper reviews recent literature on
      respiratory health in women in relation to age at menarche, menstrual cycle,
      irregular menstruation, polycystic ovarian syndrome, menopause and exogenous sex
      hormones. This literature provides substantial evidence that hormonal status
      plays an important role for respiratory health in women. Effects of hormonal
      status on the airways often appear to be heterogeneous and recent literature in
      particular suggests that the interplay between hormonal and metabolic factors is
      important. A view to developmental factors may also be relevant for the
      understanding of respiratory health according to hormonal status in women.
      Further knowledge of respiratory health in women holds interesting potential for
      intervention and personalized treatment.

PMID- 22455492
TI  - Biomarkers in community-acquired pneumonia.
AB  - A relevant problem in the management of pulmonary infections is the low
      specificity of clinical symptoms for the exact diagnosis and the need of
      antibiotic therapy. An ideal biomarker for bacterial pulmonary infections should
      allow a rapid diagnosis, have a prognostic value and facilitate therapeutic
      decision making. The two biomarkers currently needed in clinical use are C
      reactive protein and procalcitonin. C-reactive protein is very unspecific and
      elevated in bacterial as well as viral infections. Today, procalcitonin is the
      best validated biomarker for pulmonary infections. In several interventional
      studies procalcitonin-guided therapy has proven to allow a significant reduction
      of duration and frequency of antibiotic therapy. However, for the evaluation of
      prognosis in community-acquired pneumonia, new cardiovascular biomarkers are
      superior compared with inflammatory markers, especially for the determination of
      long-term mortality. The combination of several biomarkers reflecting different
      pathophysiological pathways has the potential to improve the management of
      community-acquired pneumonia in the future.

PMID- 22455493
TI  - Identifying targets in the hunt for effective respiratory syncytial virus
      interventions.
AB  - Respiratory syncytial virus (RSV) is a major cause of human infections worldwide.
      There is currently no effective vaccine or antiviral therapy available for
      widespread clinical use; prophylaxis with anti-RSV antibodies is used in only a
      small percentage of potential recipients. New targets for effective RSV
      interventions are needed. Previous anti-RSV intervention strategies have focused
      on targeting aspects of the virus, an approach that can lead to the emergence of
      resistant RSV strains. Increased understanding of the biology of RSV-host
      interactions provides an alternative approach for identifying novel targets for
      RSV interventions that focus on host factors, and exploiting them with the aim to
      limit the incidence and severity of RSV infections.

PMID- 22455494
TI  - Genetic basis for personalized medicine in asthma.
AB  - There is heterogeneity in patient responses to current asthma medications.
      Significant progress has been made identifying genetic polymorphisms that
      influence the efficacy and potential for adverse effects to asthma drugs,
      including; beta(2)-adrenergic receptor agonists, corticosteroids and leukotriene
      modifiers. Pharmacogenetics holds great promise to maximise clinical outcomes and
      minimize adverse effects. Asthma is heterogeneous with respect to clinical
      presentation and inflammatory mechanisms underlying the disease, which is likely
      to contribute to variable results in clinical trials targeting specific
      inflammatory mediators. Genome-wide association studies have begun to identify
      genes underlying asthma (e.g., IL1RL1), which represent future therapeutic
      targets. In this article, we review and update the pharmacogenetics of current
      asthma therapies and discuss the genetics underlying selected Phase II and future
      targets.

PMID- 22455495
TI  - Changes of protein profile in fresh-cut lotus tuber before and after browning.
AB  - Browning is a critical problem, which often limits the shelf life and
      marketability in fresh-cut lotus tuber. Proteome level changes in response to the
      browning metabolism were investigated using two-dimensional electrophoresis (2
      DE) and MALDI-TOF-TOF. A total of 34 functional protein spots were identified by
      comparing 2-DE protein patterns of fresh-cut lotus tuber before and after
      browning. These 34 identified proteins could be classified into 7 functional
      groups based on the NCBI database, that is, material and energy metabolism (35%),
      stress response (20%), respiration metabolism (12%), cell structure (12%), signal
      transduction (6%), gene expression regulation (6%), and unclassified proteins
      (9%). The group with the greatest difference in protein expression was related to
      material metabolism and regulation, reactive oxygen species metabolism, and
      respiratory control. The distinct proteins included universal stress protein
      (USP), superoxide dismutase (SOD), peroxidase (POD), ferritin, and ATPase.

PMID- 22455497
TI  - Electrically conducting polymers as templating interfaces for fabrication of
      copper nanotubes.
AB  - Submicrometer tubes have been fabricated by a polymer-based template approach
      using electroless deposition. The copper was deposited on polystyrene fibers
      functionalized with an interfacial electrically conducting polyaniline thin film
      layer. Thermal degradation of the functionalized fiber templates resulted in
      copper tubes of diameter 1600 +/- 50 nm with wall thicknesses ranging between 100
      and 200 nm. The morphology and elemental analysis of copper coaxial fibers was
      analyzed using SEM and EDS. Electrical properties were analyzed using FTIR and
      PXRD was used to study crystal structure of copper nanotubes. 

PMID- 22455498
TI  - Structure of geranyl diphosphate C-methyltransferase from Streptomyces coelicolor
      and implications for the mechanism of isoprenoid modification.
AB  - Geranyl diphosphate C-methyltransferase (GPPMT) from Streptomyces coelicolor
      A3(2) is the first methyltransferase discovered that modifies an acyclic
      isoprenoid diphosphate, geranyl diphosphate (GPP), to yield a noncanonical
      acyclic allylic diphosphate product, 2-methylgeranyl diphosphate, which serves as
      the substrate for a subsequent cyclization reaction catalyzed by a terpenoid
      cyclase, methylisoborneol synthase. Here, we report the crystal structures of
      GPPMT in complex with GPP or the substrate analogue geranyl S-thiolodiphosphate
      (GSPP) along with S-adenosyl-L-homocysteine in the cofactor binding site,
      resulting from in situ demethylation of S-adenosyl-L-methionine, at 2.05 or 1.82
      A resolution, respectively. These structures suggest that both GPP and GSPP can
      undergo catalytic methylation in crystalline GPPMT, followed by dissociation of
      the isoprenoid product. S-Adenosyl-L-homocysteine remains bound in the active
      site, however, and does not exchange with a fresh molecule of cofactor S-adenosyl
      L-methionine. These structures provide important clues about the molecular
      mechanism of the reaction, especially with regard to the face of the 2,3 double
      bond of GPP that is methylated as well as the stabilization of the resulting
      carbocation intermediate through cation-pi interactions.

PMID- 22455499
TI  - Peptide vectors for the nonviral delivery of nucleic acids.
AB  - Over the past two decades, gene therapy has garnered tremendous attention and is
      heralded by many as the ultimate cure to treat diseases such as cancer, viral
      infections, and inherited genetic disorders. However, the therapeutic
      applications of nucleic acids extend beyond the delivery of double-stranded DNA
      and subsequent expression of deficient gene products in diseased tissue. Other
      strategies include antisense oligonucleotides and most notably RNA interference
      (RNAi). Antisense strategies bear great potential for the treatment of diseases
      that are caused by misspliced mRNA, and RNAi is a universal and extraordinarily
      efficient tool to knock down the expression of virtually any gene by specific
      degradation of the desired target mRNA. However, because of the hurdles
      associated with effective delivery of nucleic acids across a cell membrane, the
      initial euphoria surrounding siRNA therapy soon subsided. The ability of
      oligonucleotides to cross the plasma membrane is hampered by their size and
      highly negative charge. Viral vectors have long been the gold standard to
      overcome this barrier, but they are associated with severe immunogenic effects
      and possible tumorigenesis. Cell-penetrating peptides (CPPs), cationic peptides
      that can translocate through the cell membrane independent of receptors and can
      transport cargo including proteins, small organic molecules, nanoparticles, and
      oligonucleotides, represent a promising class of nonviral delivery vectors. This
      Account focuses on peptide carrier systems for the cellular delivery of various
      types of therapeutic nucleic acids with a special emphasis on cell-penetrating
      peptides. We also emphasize the clinical relevance of this research through
      examples of promising in vivo studies. Although CPPs are often derived from
      naturally occurring protein transduction domains, they can also be artificially
      designed. Because CPPs typically include many positively charged amino acids,
      those electrostatic interactions facilitate the formation of complexes between
      the carriers and the oligonucleotides. One drawback of CPP-mediated delivery
      includes entrapment of the cargo in endosomes because uptake tends to be
      endocytic: coupling of fatty acids or endosome-disruptive peptides to the CPPs
      can overcome this problem. CPPs can also lack specificity for a single cell type,
      which can be addressed through the use of targeting moieties, such as peptide
      ligands that bind to specific receptors. Researchers have also applied these
      strategies to cationic carrier systems for nonviral oligonucleotide delivery,
      such as liposomes or polymers, but CPPs tend to be less cytotoxic than other
      delivery vehicles.

PMID- 22455500
TI  - Hierarchically driven IrO2 nanowire electrocatalysts for direct sensing of
      biomolecules.
AB  - Applying nanoscale device fabrications toward biomolecules, ultra sensitive,
      selective, robust, and reliable chemical or biological microsensors have been one
      of the most fascinating research directions in our life science. Here we
      introduce hierarchically driven iridium dioxide (IrO(2)) nanowires directly on a
      platinum (Pt) microwire, which allows a simple fabrication of the amperometric
      sensor and shows a favorable electronic property desired for sensing of hydrogen
      peroxide (H(2)O(2)) and dihydronicotinamide adenine dinucleotide (NADH) without
      the aid of enzymes. This rational engineering of a nanoscale architecture based
      on the direct formation of the hierarchical 1-dimensional (1-D) nanostructures on
      an electrode can offer a useful platform for high-performance electrochemical
      biosensors, enabling the efficient, ultrasensitive detection of biologically
      important molecules.

PMID- 22455501
TI  - Seroprevalence of hepatitis B e antigen (HBe antigen) and B core antibodies (IgG
      anti-HBcore and IgM anti-HBcore) among hepatitis B surface antigen positive blood
      donors at a Tertiary Centre in Nigeria.
AB  - BACKGROUND: Hepatitis B virus (HBV) is a common cause of liver disease throughout
      the world. HBV is transmitted through blood and other body fluids, including
      semen and saliva. Chronic replication of HBV virons is characterized by
      persistence circulation of HBsAg, HBeAg and HBV DNA; usually with anti-HBc and
      occasionally with anti-HBs. AIM: To determine the prevalence of HBeAg, IgG anti
      HBcore and IgM anti-HBcore amongst HBsAg positive blood donors. These parameters
      are reflective of transmissibility and active hepatitis B infection. A cross
      sectional study was carried out at the blood donor clinics of Lagos State
      University Teaching Hospital Ikeja and Lagos University Teaching Hospital
      Idiaraba. A total of 267 donors were recruited to determine HBe antigen, IgG and
      IgM anti-HBcore antibodies amongst hepatitis BsAg positive donors. Five
      milliliters of blood was collected from those who tested positive to HBsAg screen
      during donation. The sera were subjected to enzyme linked immunosorbent assay
      (ELISA). Pearson chi-squared test was used for the analytical assessment.
      FINDINGS: A total number of 267 HBsAg positive blood donors were studied. A
      seroprevalence of 8.2% (22 of 267) HBeAg was obtained, 4 of 267 (1.5%) were
      indeterminate while 241 (90.3%) tested negative. Only 27 out of 267 donors
      (10.1%) tested positive to IgM anti-HBcore, 234(87.6%) tested negative, while
      6(2.2%) were indeterminate. A higher percentage of 60.7% (162 of 267) tested
      positive to IgG anti-HBcore, while 39.3% (105 of 267) tested negative.
      CONCLUSION: There is a low seroprevalence rate of HBeAg-positive chronic
      hepatitis and relatively high IgG anti-HBcore and IgM anti-HBcore rates in South
      West Nigeria.

PMID- 22455502
TI  - Advances in hepatitis C virus vaccines, part two: advances in hepatitis C virus
      vaccine formulations and modalities.
AB  - INTRODUCTION: Developing a vaccine against HCV is an important medical and global
      priority. Unavailability and potential dangers associated with using attenuated
      HCV viral particles for vaccine preparation have resulted in the use of HCV genes
      and proteins formulated in novel vaccine modalities. AREAS COVERED: In part one
      of this review, advances in basic knowledge for HCV vaccine design were provided.
      Herein, a detailed and correlated patents (searched by Espacenet) and literatures
      (searched by Pubmed) review on HCV vaccine formulations and modalities is
      provided, including: subunit, DNA, epitopic-peptide/polytopic, live vector- and
      whole yeast-based vaccines. Less-touched areas in vaccine studies such as
      mucosal, plant-based, and chimeric HBV/HCV vaccines are also discussed.
      Furthermore, results of preclinical/clinical studies on selected HCV vaccines as
      well as pros and cons of different strategies are reviewed. Finally, potential
      strategies for creation and/or improvement of HCV vaccine formulations are
      discussed. EXPERT OPINION: Promising outcomes of a few HCV vaccine modalities in
      phase I/II clinical trials predict the accessibility of at least partially
      effective vaccines to inhibit or treat the chronic state of HCV infection
      (specially in combination with standard antiviral therapy). ChronVac-C (plasmid
      DNA), TG4040 (MVA-based), and GI-5005 (whole yeast-based) might be the most
      obvious HCV vaccine candidates to be approved in the near future.

PMID- 22455503
TI  - The immunoregulatory effects of CMV-infection in human fibroblasts and the impact
      on cellular senescence.
AB  - BACKGROUND: As a chronic antigenic stressor human Cytomegalovirus (CMV)
      contributes substantially to age-related alterations of the immune system. Even
      though monocytes have the greatest propensity for CMV-infection and seem to be an
      important host for the virus during latency, fibroblasts are also discussed to be
      target cells of CMV in vivo. However, little is known so far about general
      immunoregulatory properties of CMV in fibroblasts. We therefore investigated the
      immunoregulatory effects of CMV-infection in human lung fibroblasts and the
      impact on replicative senescence. FINDINGS: We observed that CMV-infection led to
      the induction of several immunoregulatory host cell genes associated with the
      innate and adaptive immune system. These were genes of different function such as
      genes regulating apoptosis, cytokines/chemokines and genes that are responsible
      for the detection of pathogens. Some of the genes upregulated following CMV
      infection are also upregulated during cellular senescence, indicating that CMV
      causes an immunological phenotype in fibroblasts, which is partially reminiscent
      of replicative senescent cells. CONCLUSION: In summary our results demonstrate
      that CMV not only affects the T cell pool but also induces inflammatory processes
      in human fibroblasts.

PMID- 22455504
TI  - Cocaine and acute vascular diseases.
AB  - Cocaine is one of the most widely used drugs of abuse. Chest pain is the most
      common side effect requiring emergency visits after cocaine use. Vasoconstriction
      and platelet activation are the main effects of cocaine in the vasculature. In
      this brief review, we consider the most important clinical effects of cocaine
      abuse on the heart, brain and kidney. Symptoms related to cocaine toxicity such
      as myocardial infarction, congestive heart failure, arrhythmias, aortic
      dissection, stroke, renal failure, are similar to the clinical picture of
      atherosclerotic vascular damage, even if the age of cocaine abusers is usually in
      the second and third decades. Clinicians (especially emergency department
      physicians) should consider substance abuse among the differential diagnosis of
      chest pain in young people.

PMID- 22455505
TI  - Romantic relationships and alcohol use.
AB  - The focus of this review is on the associations of alcohol use and aspects of
      romantic relationships. The review covers concepts and methods, partner drinking
      associations, effects of relationships on drinking, and drinking effects on
      relationships. Several conclusions were reached. People are attracted to
      similarly drinking others. With greater relationship commitment there is greater
      desistance from drinking. Across time and relationship commitment levels,
      socialization influences vary by gender. A thread throughout the review was the
      identification of congruent and discrepant drinking among relationship partners.
      Congruent drinking, even at higher levels, was associated with more positive
      outcomes whereas discrepant drinking was associated with more negative outcomes.
      Needed for the future are greater theory development and longitudinal and
      laboratory studies that include diverse samples and both parties to the
      relationship.

PMID- 22455506
TI  - Efficacy of group treatments for alcohol use disorders: a review.
AB  - This paper reviews the efficacy and processes of change within group treatments
      for alcohol use disorders (AUD). Methodologically rigorous studies examining
      group treatment for interviewer-diagnosed AUD include evaluations of cognitive
      behavioral group treatments that focus on skills for relapse prevention (i.e.,
      coping skills training, coping and social skills training), interactional group
      therapy, combined pharmacological and group interventions, and group cue exposure
      treatment. Given the depth of research examining the efficacy of individual
      treatments for AUD there is a need for further development and evaluation of
      group treatments that include rigorous clinician-administered diagnostic
      assessment, implement a control group or active treatment comparison, randomly
      assign participants to condition, report the racial and ethnic composition of the
      sample, explore mediators and moderators of intervention efficacy, and implement
      a manualized treatment protocol. Evaluation of process variables within group
      treatments for AUD and well designed treatment development studies are also
      needed to better understand how well established individual treatments for
      alcohol use disorders can be adapted to function effectively in a group format.

PMID- 22455507
TI  - Alcohol and cognition - consideration of age of initiation, usage patterns and
      gender: a brief review.
AB  - Heavy alcohol use has numerous negative impacts on cognition. In many cases, it
      appears that excess drinking influences working memory, problem solving,
      attention, patterns of regional brain activation, and even gray and white matter
      volume. Due to these effects, most significant conclusions related to cognitive
      decline are limited to the assumption that "more is worse." However, heavy
      alcohol use is a very complex psychosocial behavior and is subject to a
      problematic number of variables. As a result, it is very difficult to extend
      generalizations about drinking-related consequences to the overall population
      since many environmental and biological differences come into play for every
      individual. Three of these variables shown to have significant impact on
      cognitive sensitivity to alcohol are age of first alcohol use (age of drinking
      initiation), specific pattern of alcohol consumption and gender. Potential
      insight can be gained into how individual drinking scenarios differ in risk for
      cognitive decline by assessing how each of these important factors influences
      cognition independently. Although some overlap exists between categories, each
      still appears to contribute unique influence on likelihood and presentation of
      cognition-related effects. Based on existing and current research, age and gender
      tend to augment baseline sensitivity to alcohol, with patterns of alcohol intake
      also influencing how changes appear. Given these categorical differences, it is
      important to consider personal alcohol drinking history rather than just
      aggregate alcohol intake as risk factors in the cognitive impacts of drinking.
      The objective of this brief review is to examine the role of these factors on the
      effect of alcohol on cognition.

PMID- 22455508
TI  - The association between alcohol use and sexual risk behaviors among African
      American women across three developmental periods: a review.
AB  - BACKGROUND: African American women experience increased rates of sexually
      transmitted diseases and HIV. The use of alcohol may increase sexual risk
      behaviors among this population. PURPOSE: This paper provides a review and
      critique of the literature examining the association between alcohol use and
      sexual risk behaviors among African American females including a: (a) synthesis
      of research findings from adolescent, college-aged/early adulthood, and adult
      samples; (b) methodological critique of the literature; and (c) guidance for
      future research. METHODS: We reviewed 32 studies examining the association
      between alcohol use and sexual risk behaviors among African American females
      across developmental periods. RESULTS: Similar to previous association studies,
      results suggest that increased use of alcohol is associated with increased sexual
      risk practices among African American females. Further, even non-abuse levels of
      drinking among African American females, at all ages, were related to increased
      sexual risk-taking. CONCLUSIONS: Future studies should seek to recruit samples
      that more fully reflect the diversity of African American women's experiences
      across the lifespan. Given the association between alcohol use and/or abuse and
      the prevalence of STI/HIV-associated risk behaviors and adverse biological
      outcomes (i.e., STIs, including HIV) among African American females across the
      lifespan, there is a clear need to develop and evaluate prevention research
      efforts tailored for this subgroup.

PMID- 22455509
TI  - Understanding the diverse needs of children whose parents abuse substances.
AB  - In this review, we consider the potential service needs of children of substance
      abusing parents based on what we know about the risk outcomes faced by these
      children and the parenting deficits often present in these families. Importantly,
      our review does not address the etiological role of parental substance abuse in
      children's negative outcomes but instead we discuss the complex inter-related
      risk factors that often co-occur with and exacerbate risk associated with
      parental alcohol and drug use. We first review studies showing the elevated risk
      that children of substance abusing parents face in general for poorer academic
      functioning; emotional, behavioral, and social problems; and an earlier onset of
      substance use, faster acceleration in substance use patterns, and higher rates of
      alcohol and drug use disorders. We then review studies showing contextual risk
      factors for children of substance abusing parents, including parenting deficits
      (less warmth, responsiveness, and physical and verbal engagement as well as
      harsher and more over-involved interaction styles), greater risk for child
      maltreatment, and less secure attachment patterns. We conclude with a discussion
      of future directions for research and guidelines for professionals working with
      children and their families where parental substance abuse is present.

PMID- 22455510
TI  - Vessel motion thresholds for maintaining physical and cognitive performance: a
      study of naval personnel at sea.
AB  - Methods and results are reported from a study of ships companies' exposure to low
      frequency motions on three vessels of the Royal Navy. The aim of the study was to
      investigate relationships between deck accelerations and the incidence of
      problems such as difficulties with physical tasks, cognitive activities, motion
      sickness, and work effort. Ship motions were recorded continuously during sea
      patrols of 10-14 days. The data collected from the three vessels comprised 105
      days of ship motions over 12 patrols, with 779 associated daily diaries from 78
      participants. Problems most strongly associated with vessel motions were related
      to the difficulties with physical tasks. Some cognitive aspects of task
      performance and motion sickness were associated with vertical acceleration
      magnitudes, but the correlations were less strong than with physical tasks.   
      Practitioner Summary: Little is known about the severity of ship motions that
      degrade physical and mental performance. The paper offers preliminary estimates
      of the motion threshold values below which the performance will not be degraded
      by motion.

PMID- 22455511
TI  - Intravenous non-high-dose pantoprazole is equally effective as high-dose
      pantoprazole in preventing rebleeding among low risk patients with a bleeding
      peptic ulcer after initial endoscopic hemostasis.
AB  - BACKGROUND: Many studies have shown that high-dose proton-pumps inhibitors (PPI)
      do not further reduce the rate of rebleeding compared to non-high-dose PPIs but
      we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates
      among patients at low risk (Rockall score < 6) or among those at high risk, both
      compared to high-dose PPIs. This retrospective case-controlled study aimed to
      identify the subgroups of these patients that might benefit from treatment with
      non-high-dose PPIs. METHODS: Subjects who received high dose and non-high-dose
      pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were
      enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and
      rebleeding groups (n = 89). The greedy method was applied to allow treatment
      control random matching (1:1). Patients were randomly selected from the non-high
      dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104
      in each group), and these were then subdivided to two subgroups (Rockall score >=
      6 vs. < 6, n = 77 vs. 27). RESULTS: An initial low hemoglobin level, serum
      creatinine level, and Rockall score were independent factors associated with
      rebleeding. After case-control matching, the significant variables between the
      non-high-dose and high-dose PPI groups for a Rockall score >= 6 were the
      rebleeding rate, and the amount of blood transfused. Case-controlled matching for
      the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar
      for both groups (11.1% in each group). CONCLUSION: Intravenous non-high-dose
      pantoprazole is equally effective as high-dose pantoprazole when treating low
      risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk
      stigmata after endoscopic hemostasis.

PMID- 22455512
TI  - Infrared multiple-photon dissociation spectroscopy of tripositive ions: lanthanum
      tryptophan complexes.
AB  - Collision-induced charge disproportionation limits the stability of triply
      charged metal ion complexes and has thus far prevented successful acquisition of
      their gas-phase IR spectra. This has curtailed our understanding of the
      structures of triply charged metal complexes in the gas phase and in biological
      environments. Herein we report the first gas-phase IR spectra of triply charged
      La(III) complexes with a derivative of tryptophan (N-acetyl tryptophan methyl
      ester), and an unusual dissociation product, a lanthanum amidate. These spectra
      are compared with those predicted using density functional theory. The best
      structures are those of the lowest energies that differ by details in the pi
      interaction between La(3+) and the indole rings. Other binding sites on the
      tryptophan derivative are the carbonyl oxygens. In the lanthanum amidate, La(3+)
      replaces an H(+) in the amide bond of the tryptophan derivative.

PMID- 22455513
TI  - Inhibition assay of yeast cell walls by plasmon resonance Rayleigh scattering and
      surface-enhanced Raman scattering imaging.
AB  - We report on plasmon resonance Rayleigh scattering (PRRS) and surface enhanced
      Raman scattering (SERS) imaging for inhibition assay of yeast cell walls. This
      assay reveals that the proteins having alkali sensitive linkage bound to beta1,3
      glucan frameworks in cell walls are involved in SERS activity. The result is
      further confirmed by comparison of genetically modified cells and wild type
      cells. Finally, we find that PRRS and SERS spots do not appear on cell walls when
      daughter cells are enough smaller than parent ones, but appear when size of
      daughter cells are comparable to parent cells. This finding indicates the
      relationship between expression of the proteins that generate SERS spots and cell
      division. These results demonstrate that PRRS and SERS imaging can be a
      convenient and sensitive method for analysis of cell walls.

PMID- 22455515
TI  - Asphalt, water, and the prebiotic synthesis of ribose, ribonucleosides, and RNA.
AB  - RNA has been called a "prebiotic chemist's nightmare" because of its combination
      of large size, carbohydrate building blocks, bonds that are thermodynamically
      unstable in water, and overall intrinsic instability. However, a discontinuous
      synthesis model is well-supported by experimental work that might produce RNA
      from atmospheric CO(2), H(2)O, and N(2). For example, electrical discharge in
      such atmospheres gives formaldehyde (HCHO) in large amounts and glycolaldehyde
      (HOCH(2)CHO) in small amounts. When rained into alkaline aquifers generated by
      serpentinizing rocks, these substances were undoubtedly converted to
      carbohydrates including ribose. Likewise, atmospherically generated HCN was
      undoubtedly converted in these aquifers to formamide and ammonium formate,
      precursors for RNA nucleobases. Finally, high reduction potentials maintained by
      mantle-derived rocks and minerals would allow phosphite to be present in
      equilibrium with phosphate, mobilizing otherwise insoluble phosphorus for the
      prebiotic synthesis of phosphite and phosphate esters after oxidation.  So why
      does the community not view this discontinuous synthesis model as compelling
      evidence for the RNA-first hypothesis for the origin of life? In part, the model
      is deficient because no experiments have joined together those steps without
      human intervention. Further, many steps in the model have problems. Some are
      successful only if reactive compounds are presented in a specific order in large
      amounts. Failing controlled addition, the result produces complex mixtures that
      are inauspicious precursors for biology, a situation described as the "asphalt
      problem". Many bonds in RNA are thermodynamically unstable with respect to
      hydrolysis in water, creating a "water problem". Finally, some bonds in RNA
      appear to be "impossible" to form under any conditions considered plausible for
      early Earth.  To get a community-acceptable "RNA first" model for the origin of
      life, the discontinuous synthesis model must be developed. In particular, the
      model must be refined so that it yields oligomeric RNA from CO(2), H(2)O, and
      N(2) without human intervention. This Account describes our efforts in this
      direction.  Our hypothesis centers on a geological model that synthesizes RNA in
      a prebiotic intermountain dry valley (not in a marine environment). This valley
      receives high pH run-off from a watershed rich in serpentinizing olivines and
      eroding borate minerals. The runoff contains borate-stabilized carbohydrates,
      formamide, and ammonium formate. As atmospheric CO(2) dissolves in the subaerial
      aquifer, the pH of the aquifer is lowered. In the desert valley, evaporation of
      water, a solvent with a nucleophilic "background reactivity", leaves behind
      formamide, a solvent with an electrophilic "background reactivity". As a result,
      nucleobases, formylated nucleobases, and formylated carbohydrates, including
      formylated ribose, can form. Well-known chemistry transforms these structures
      into nucleosides, nucleotides, and partially formylated oligomeric RNA.

PMID- 22455514
TI  - Structure of 2-methylisoborneol synthase from Streptomyces coelicolor and
      implications for the cyclization of a noncanonical C-methylated monoterpenoid
      substrate.
AB  - The crystal structure of 2-methylisoborneol synthase (MIBS) from Streptomyces
      coelicolor A3(2) has been determined in complex with substrate analogues geranyl
      S-thiolodiphosphate and 2-fluorogeranyl diphosphate at 1.80 and 1.95 A
      resolution, respectively. This terpenoid cyclase catalyzes the cyclization of the
      naturally occurring, noncanonical C-methylated isoprenoid substrate, 2
      methylgeranyl diphosphate, to form the bicyclic product 2-methylisoborneol, a
      volatile C(11) homoterpene alcohol with an earthy, musty odor. While MIBS adopts
      the tertiary structure of a class I terpenoid cyclase, its dimeric quaternary
      structure differs from that previously observed in dimeric terpenoid cyclases
      from plants and fungi. The quaternary structure of MIBS is nonetheless similar in
      some respects to that of dimeric farnesyl diphosphate synthase, which is not a
      cyclase. The structures of MIBS complexed with substrate analogues provide
      insights regarding differences in the catalytic mechanism of MIBS and the
      mechanisms of (+)-bornyl diphosphate synthase and endo-fenchol synthase, plant
      cyclases that convert geranyl diphosphate into products with closely related
      bicyclic bornyl skeletons, but distinct structures and stereochemistries.

PMID- 22455516
TI  - Hepatitis C virus-specific cellular immune responses in individuals with no
      evidence of infection.
AB  - The detection of hepatitis C virus (HCV)-specific T cell responses in HCV
      uninfected, presumably unexposed, subjects could be due to an underestimation of
      the frequency of spontaneously resolving infections, as most acute HCV infections
      are clinically silent. To address this hypothesis, HCV-specific cellular immune
      responses were characterized, in individuals negative for an HCV PCR assay and
      humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV.
      Uninfected volunteers (n = 20) with a chronically HCV-infected partner were
      included as positive controls for potential exposure to HCV and HCV infection,
      respectively. HCV-specific T cell responses in freshly isolated peripheral blood
      mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation
      assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated
      peptides was used as a negative control, and a peptide mix of human
      cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control.
      Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell
      responses to the virus, a rate much higher than previous estimates of HCV
      prevalence in developed countries. This result would be consistent with
      unapparent primary HCV infections that either cleared spontaneously or remained
      undetected by conventional serological assays.

PMID- 22455517
TI  - Immunoaffinity chromatography purification and ultra-high-performance liquid
      chromatography-tandem mass spectrometry determination of four beta-agonists in
      beef.
AB  - A highly selective and sensitive method was developed for the simultaneous
      determination of four beta-agonists (clenbuterol, salbutamol, ractopamine and
      terbutaline) in beef by immunoaffinity chromatography purification coupled to
      ultra-high-performance LC-MS/MS. The MS/MS conditions, ultra-high-performance LC
      mobile phase, injection solution, sample purification process and matrix effect
      were studied to optimise the operation conditions. The limits of detection (LODs)
      of the instrument for the studied beta-agonists ranged from 0.20 to 0.25 ug l(
      1), and the LODs of the method for the studied beta-agonists ranged from 0.20 to
      3.00 ug kg(-1) for beef. Calibration curves were constructed using a standard
      solution diluted with blank beef matrix. The linear ranges of the calibration
      curves ranged from 5 to 100 ug kg(-1) and the coefficients of determination were
      >0.9942 (n = 10) for all four beta-agonists. Samples spiked at 5, 10 and 50 ug
      kg(-1) showed recoveries >72% and RSDs <6.6%. The method is suitable for the
      simultaneous detection of four beta-agonists at trace levels in beef.

PMID- 22455518
TI  - Observed differences in upper extremity forces, muscle efforts, postures,
      velocities and accelerations across computer activities in a field study of
      office workers.
AB  - This study, a part of the PRedicting Occupational biomechanics in OFfice workers
      (PROOF) study, investigated whether there are differences in field-measured
      forces, muscle efforts, postures, velocities and accelerations across computer
      activities. These parameters were measured continuously for 120 office workers
      performing their own work for two hours each. There were differences in nearly
      all forces, muscle efforts, postures, velocities and accelerations across
      keyboard, mouse and idle activities. Keyboard activities showed a 50% increase in
      the median right trapezius muscle effort when compared to mouse activities.
      Median shoulder rotation changed from 25 degrees internal rotation during
      keyboard use to 15 degrees external rotation during mouse use. Only keyboard use
      was associated with median ulnar deviations greater than 5 degrees. Idle
      activities led to the greatest variability observed in all muscle efforts and
      postures measured. In future studies, measurements of computer activities could
      be used to provide information on the physical exposures experienced during
      computer use.    Practitioner Summary: Computer users may develop musculoskeletal
      disorders due to their force, muscle effort, posture and wrist velocity and
      acceleration exposures during computer use. We report that many physical
      exposures are different across computer activities. This information may be used
      to estimate physical exposures based on patterns of computer activities over
      time.

PMID- 22455519
TI  - Addition of aluminum and gallium species to aromatic and alkyl-substituted 1,4
      diaza-1,3-butadiene ligands.
AB  - In this report, we investigate the interactions of Me(x)MCl(3-x) (x = 0-3, M =
      Al, Ga) with various aromatic and alkyl-substituted 1,4-diaza-1,3-butadiene
      (R)DAB ligands (or alpha-diimine ligands) to give a variety of structures in
      solution and in the solid state. In combination with other previously reported
      structures, certain general trends of reactivity of these species can be deduced,
      although there are still some unexplained modes of reactivity. The methylated Al
      species react with aromatic-substituted (R)DAB ligands to provide final products
      that result from C?N insertion into the Al-CH(3) group followed by rearrangement
      reactions. The addition of methyl groups onto the backbone of the (R)DAB ligand
      is insufficient to stop the insertion and rearrangement processes from occurring.
      In the case of MeAlCl(2) with the bulky (DiPP)DAB ligand, the reaction could be
      followed spectroscopically from the monoadduct through the inserted/rearranged
      final product. Methylated Ga species, however, are much less predictable in their
      behavior with aromatic-substituted (R)DAB ligands. Depending on the exact species
      and ratios used, coordinated adducts can be formed and identified, or
      inserted/rearranged products similar to the aluminum reactions can be obtained.
      Quite interestingly, cation/anion pairs can also be formed in which GaCl(3) or
      MeGaCl(2) act as a chloride acceptors. This behavior was unique and substantially
      different from the analogous Al reactions which formed either a dicoordinated
      adduct or an inserted/rearranged complex. When the stronger-donating alkyl
      substituted (R)DAB ligands were used with Me(2)GaCl, only cation/anion pairs were
      obtained. Surprisingly, when the same reactions were performed using Me(2)AlCl as
      a reagent, irreproducible results were obtained.

PMID- 22455520
TI  - Validation of the Spiritual Distress Assessment Tool in older hospitalized
      patients.
AB  - BACKGROUND: The Spiritual Distress Assessment Tool (SDAT) is a 5-item instrument
      developed to assess unmet spiritual needs in hospitalized elderly patients and to
      determine the presence of spiritual distress. The objective of this study was to
      investigate the SDAT psychometric properties. METHODS: This cross-sectional study
      was performed in a Geriatric Rehabilitation Unit. Patients (N = 203), aged 65
      years and over with Mini Mental State Exam score >= 20, were consecutively
      enrolled over a 6-month period. Data on health, functional, cognitive, affective
      and spiritual status were collected upon admission. Interviews using the SDAT
      (score from 0 to 15, higher scores indicating higher distress) were conducted by
      a trained chaplain. Factor analysis, measures of internal consistency (inter-item
      and item-to-total correlations, Cronbach alpha), and reliability (intra-rater and
      inter-rater) were performed. Criterion-related validity was assessed using the
      Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp)
      and the question "Are you at peace?" as criterion-standard. Concurrent and
      predictive validity were assessed using the Geriatric Depression Scale (GDS),
      occurrence of a family meeting, hospital length of stay (LOS) and destination at
      discharge. RESULTS: SDAT scores ranged from 1 to 11 (mean 5.6 +/- 2.4). Overall,
      65.0% (132/203) of the patients reported some spiritual distress on SDAT total
      score and 22.2% (45/203) reported at least one severe unmet spiritual need. A two
      factor solution explained 60% of the variance. Inter-item correlations ranged
      from 0.11 to 0.41 (eight out of ten with P < 0.05). Item-to-total correlations
      ranged from 0.57 to 0.66 (all P < 0.001). Cronbach alpha was acceptable (0.60).
      Intra-rater and inter-rater reliabilities were high (Intraclass Correlation
      Coefficients ranging from 0.87 to 0.96). SDAT correlated significantly with the
      FACIT-Sp, "Are you at peace?", GDS (Rho -0.45, -0.33, and 0.43, respectively, all
      P < .001), and LOS (Rho 0.15, P = .03). Compared with patients showing no
      severely unmet spiritual need, patients with at least one severe unmet spiritual
      need had higher odds of occurrence of a family meeting (adjOR 4.7, 95%CI 1.4
      16.3, P = .02) and were more often discharged to a nursing home (13.3% vs 3.8%; P
      = .027). CONCLUSIONS: SDAT has acceptable psychometrics properties and appears to
      be a valid and reliable instrument to assess spiritual distress in elderly
      hospitalized patients.

PMID- 22455521
TI  - Paediatric aesthetic dentistry: a review.
AB  - AIM: A number of conditions can lead to aesthetically unacceptable dentitions
      like dental caries, discoloration,  trauma, early loss of teeth, misalignment and
      any abnormality of shape and size. Today we have a large number of solutions 
      available for aesthetic problems in paediatric dentistry. But the biggest dilemma
      is: How to choose what is best for a particular  patient and that situation?
      Through this review we try to precisely highlight the various options for
      aesthetic restorations  along with their indications, advantages and
      disadvantages. METHODS: A search and analysis of international works on 
      aesthetics in paediatric dentistry is presented. RESULTS: A considerable number
      of studies have shown that people are  more concerned about missing anterior
      teeth and their replacement than about posterior ones as aesthetics seems to be 
      more important than function. CONCLUSION: Dental caries, although not life
      threatening, causes nagging pain and physical  as well as psychological
      discomfort. Nevertheless, it is clear that the condition is complex and
      multifactorial and hence it is  important to review the various approaches
      available to restore the lost aesthetics.

PMID- 22455522
TI  - Correlations between malocclusions and dyslalias.
AB  - AIM: This was to evaluate the relationship between malocclusions and dyslalias
      and to plan a multidisciplinary  approach between orthodontics and speech
      therapy. STUDY DESIGN: 880 children (448 males and 432 females) ranging in age 
      from 6 to 10 years were examined at the Department of Orthodontics at Milan
      University to determine if a relationship between  malocclusions and dyslalia
      exists and their correlations. METHODS: The children were examined by a speech
      therapist and  an orthodontist. An examination of the occlusion and phonetics was
      conducted and compared with an age-matched control  group. RESULTS: Correlations
      between malocclusion and dyslalia were found. The presence of Class III
      occlusion,  diastema, increase in overjet, presence of open and deep bite,
      asymmetry have high tendency to be associated with speech  disorders such as
      dyslalias. The presence of crowding and anterior cross bites have moderate
      tendency to be associated  with such disorders; on the contrary Class II
      occlusion, upper incisors protrusion, posterior cross bite and TMD have low 
      tendency to be associated with dyslalias. CONCLUSION: The effect of dyslalia on
      the speech organs is not constant. On the  other hand, the effect of malocclusion
      on dyslalia seems to be more relevant and more frequent and to increase 
      proportionally, depending on the severity of the malocclusion.

PMID- 22455523
TI  - Suitability of polymers as screw post materials in primary teeth: an in vitro
      study.
AB  - AIM: Primary teeth undergo physiological root resorption during the transition to
      permanent dentition. The aim of  this study was to assess the potential use of
      screw posts in core build-up for primary teeth while adequately retaining the 
      crown restoration and allowing smooth physiological root resorption. METHODS: To
      determine whether biodegradable  polymers such as polyglycolic acid (PGA) and
      poly-L-lactic acid (PLLA) were appropriate as post materials, bending  strength
      test and bending elastic modulus test were performed according to ISO standards.
      The prepared screw posts were  immersed in 0.01 mol/L phosphate-buffered saline
      at 37 degrees Celsius, and changes due to hydrolysis were observed.  Results In
      the bending strength test and bending elastic modulus test, PGA and PLLA showed
      similar values to composite  resins used for core build-up. Although both showed
      adequate hydrolysis, the hydrolysis rate of PGA was higher than that of  PLLA.
      CONCLUSION: PGA and PLLA may be suitable as biodegradable screw posts for primary
      teeth because they have  appropriate strength and hydrolysis ability.

PMID- 22455524
TI  - Unilateral posterior crossbite in adolescents: surface electromyographic
      evaluation.
AB  - AIM: Unilateral posterior crossbite (UPCB) is characterised by an inverse
      relationship of the upper and lower buccal dental cusps and may involve one or
      several teeth. The aim of this study was to compare the electromyographic
      outcomes of patients with UPCB and those of healthy controls. MATERIALS AND
      METHODS: Fifteen patients (mean age 11.5 years) with UPCB and fifteen healthy
      controls (mean age 12 years) were examined at the Department of Orthodontics,
      Second University of Naples. Surface electromyography was performed on patients
      and controls. RESULTS AND CONCLUSION: Patients with UPCB had less muscle
      activation than healthy subjects (p<0.0001) and an asymmetric muscle activation
      with 89.23% muscle balancing for temporals and 83.21% for masseters. The control
      group showed a 99.32% of muscle balancing for temporals and 97.77% for masseters.
      These findings suggest that asymmetric muscle activation may influence maxillary
      and mandibular growth in adolescents with UPCB.

PMID- 22455525
TI  - Applicability of two methods of mixed dentition analysis in a contemporary Indian
      population  sample.
AB  - AIM: More than 10 years experience in implementing the Tanaka Johnston and Moyers
      methods has shown that  they overestimate the sizes of unerupted canines and
      premolars when used in populations other than the Caucasian. This  study was
      designed to assess the applicability of the two most commonly used methods of
      mixed dentition analysis and to  attempt to derive a more accurate and precise
      formula to predict the sizes of the unerupted premolars and canines in a  sample
      of Indian population. MATERIALS AND METHODS: The sample included 200 study models
      (100 male, 100 female).  Tanaka Johnston's and Moyer's equations were applied to
      this sample and the mean differences between the actual and  estimated tooth
      widths were determined. New regression equations were derived using lower first
      molars and incisors as the  predictors. RESULTS: The mean difference between the
      actual and estimated values of canines and premolars using Tanaka  Johnston's and
      Moyers methods were clinically and statistically significant. Therefore new
      regression equations were  derived taking lower first molars and incisors as the
      predictors for both sexes. On validation, these equations were found to  be
      accurate and precise for this population. CONCLUSION: It is recommended to use
      these equations as a method of mixed  dentition analysis for the Indian
      population.

PMID- 22455526
TI  - Oral Squamous Cell Carcinoma in the paediatric patient: a literature review.
AB  - AIM: Paediatric Oral Squamous Cell Carcinoma (OSCC) is rare, but its incidence is
      increasing, bringing forward  the issue of the common pathogenic factors. The aim
      of this study is to verify the actual incidence of oral carcinoma reported  in
      paediatric patients up to the age of 15 by thoroughly reviewing the available
      literature. Setting this cut-off age has allowed  us to emphasise possible risk
      factors other than those always associated with the onset of this neoplasia,
      which are not  present in this age bracket yet. METHODS: In the first stage of
      the research, generic key words concerning OSCC in  childhood were entered into
      two search engines. In the second stage, terms related to predisposing diseases
      connected to  childhood oral carcinoma and those initially found were searched.
      RESULTS: The literature review consisted of 55  documented cases from 1894 to
      2011, of which 15 were part of complete published case reports. CONCLUSION:
      Paediatric  OSCC, though uncommon, is not rare. The review has strongly
      highlighted the need to carry out an objective, thorough and  standardised
      examination of the child's oral cavity, especially when systemic predisposing
      diseases, such as Epidermolysis  bullosa, Xeroderma pigmentosum, Juvenile
      papillomatosis and Fanconi's anaemia, are present.

PMID- 22455527
TI  - The oral health environment and the equal environment assumption (EEA) among 1-8
      year-old  twins.
AB  - AIM: The purpose of the present study was to describe the oral health environment
      in preschool children and to  examine the extent to which paired twins experience
      the same oral health environment. MATERIALS AND METHODS: In  collaboration with
      The Medical Birth Registry of Norway (MBRN) 100 twin families who participated in
      the Norwegian Mother  and Child Cohort, were invited to take part in ongoing
      studies on oral health. Participating twin families lived in Oslo and the 
      surrounding counties of the capital. The age range of the participating twins was
      1-8 years. A clinical examination took place  at The Institute of Clinical
      Dentistry, University of Oslo in 2008.  The oral health environment was measured
      in two ways: 1)  Interview. Mothers were interviewed by trained interviewers
      about oral health related habits of each of the twins. 2) Weekend  diet log.
      Parents listed 84 different deserts, ice cream, sweets, cakes, cookies, fruits,
      snacks, and biscuits for each twin that  were consumed on  during the weekend.
      The statistical analyses comprised frequency distributions of the environmental 
      variables and correlations between the variables within the pair of twins.
      RESULTS: The results showed a parental  involvement in early tooth brushing and
      also an indication of tooth brushing not always being easy. Use of fluoride 
      toothpaste started early, and two thirds of the children also used fluoride
      tablets. Use of pacifier was prevalent; the duration  of use of pacifier and
      feeding bottle was relatively long. Nearly 75% of the parents indicated that they
      had no problems  relatively to the twins' meals, and 53% mentioned that the twin
      pairs were different with regard to meals. Nearly  70% of the kindergartens had a
      clear health profile. The correlations varied between r = 0.45 and 1.00.
      CONCLUSION: The children in the present work were young, and the detailed
      information in this paper therefore adds to the  knowledge of parental
      involvement in children's oral health. Generally the findings indicate a high
      level of involvement from  the parents in the oral health environment at home.
      Altogether the results showed that the assumption of identical oral health 
      environment cannot be supported by these data.

PMID- 22455528
TI  - Caries experience in 14-year-olds from Northeast Italy. Is socioeconomic-status
      (SES) still a risk factor?
AB  - AIM: Prevalence and severity of dental caries in 14-year-olds of Northeast Italy
      were estimated, evaluating the dependence to SES. MATERIALS AND METHODS: An
      epidemiological survey was performed among a randomised cluster sample of 560
      (290 M and 270 F) 14-year-olds attending secondary schools, to evaluate DMFS
      following WHO indications. Association between caries occurrence and SES was
      evaluated in a logistic regression model. To account for high proportion of zero
      scores (DMFS and DS distribution highly positively skewed) data was moreover
      modelled with negative binomial regression and zero-inflated models. RESULTS:
      Caries prevalence was 63.4% with a mean DMFS of 3.0 +/- 3.8. A significant trend
      between means was observed regarding DS in the different SES levels: z = 2.22 p =
      0.03 (occupational level) and z = 3.45 p<0.01 when SES was based on educational
      level. The Negative Binomial Regression model resulted more appropriate than the
      Poisson model because the dispersion parameter was significantly different from
      zero (alpha=1.5, 95% CI=1.3-1.8). Working class status showed significant
      association with DMFS (p=0.04) while using DS as dependent variable, working
      class subjects and subjects with medium-low and low educational level, showed a
      statistically significant association. CONCLUSION: Socioeconomic status is still
      a predictor for dental decay in the Italian 14-year-olds.

PMID- 22455529
TI  - Prevalence and intra-oral distribution of agenesis of permanent teeth among
      Eastern Turkish  children.
AB  - AIM: The aim of this study was to describe agenesis of permanent teeth, excluding
      the third molars, in a sample of  children in Eastern Turkey. MATERIALS AND
      METHODS: This retrospective study assessed 1,291 digital  orthopantomograms (OPT)
      (678 males and 613 females), taken at the Faculty of Dentistry, Ataturk
      University, Erzurum. The  chi-square test was used to compare maxillary and
      mandibular hypodontia in males and females. RESULTS: Eighty children  were found
      to have at least one tooth absent from their permanent set of teeth. The
      prevalence of tooth agenesis was  6.2%. A total of 135 permanent teeth were
      missing as a result of the congenital condition. Tooth agenesis was found  more
      frequently in females than in males. Although there was no significant difference
      between genders in the prevalence of  hypodontia among the children (p>0.05), the
      difference between genders in children who had congenitally missing teeth  (CMT)
      reached a statistically significant level (p<0.05). CONCLUSION: When hypodontia
      in a Turkish paediatric  population was compared to other populations, the
      characteristics were found to be similar to the Western population.  However, the
      population in Eastern Turkey differs from the population in Asia, where there is
      less incisor tooth agenesis and  more second molar tooth agenesis.

PMID- 22455530
TI  - Rapid maxillary expansion in children with Obstructive Sleep Apnoea Syndrome
      (OSAS).
AB  - AIM: to evaluate the effects of rapid maxillary expansion (RME) in a group of
      OSAS preschool children. MATERIALS AND METHODS: Lateral cephalograms of 15 OSAS
      children (8 boys and 7 girls, age mean +/- SD: 5.94 +/- 1.64 years) were analysed
      at the start of treatment with RME (T0). All subjects were revaluated after a
      mean period of 1.57 +/- 0.58 years (T1). At this time the sample was divided into
      2 groups according to the change in the respiratory disturbance index (RDI): an
      improved group (I: 8 subjects) and a stationary/worsened group (SW: 7 subjects).
      Differences between I and SW children with respect to values of cephalometric
      variables at T0 and to variations between T0 and T1 were evaluated using Mann
      Whitney U test. Differences between T0 and T1 values in the overall group of
      children and separately in I and SW groups were assessed using Wilcoxon test.
      RESULTS: At the start of treatment, the I group was characterised by more
      retrognathic jaws with lower values of SNA (p=0.055) and SNB (p=0.020) and higher
      age values (p=0.093) when compared to SW group. After treatment, the I group
      showed an increase in SNA and SNB angle significantly higher than SW group
      (p=0.004 and p=0.003, respectively). On the contrary, I and SW groups did not
      differ as for variation in the skeletal divergency and in the total facial
      height. CONCLUSION: OSAS preschool children with retrognathic jaws could benefit
      from RME treatment.

PMID- 22455531
TI  - Malaysian undergraduates' knowledge and opinions on Early Childhood oral health.
AB  - AIM: In Malaysia, Early Childhood Caries (ECC) was found to affect 76.2% of 5
      year-olds (2005). General  practitioners are more likely to encounter preschool
      children and are in a better position to educate parents and caretakers  about
      ECC and make appropriate referrals. This study assessed the knowledge and
      opinions on early childhood oral health  among medical and dental undergraduates.
      MATERIALS AND METHODS: This cross sectional study involved 245 students  enrolled
      in the first year medical (M1) and dental (D1) course and fourth year medical
      (M4) and dental (D4) course. The  students completed a self-administered
      questionnaire which included knowledge and opinions on early childhood oral 
      health. Comparisons between the groups were done using chi-square test. RESULTS:
      Dental students showed significantly  better knowledge than medical students. D1
      students showed significantly better knowledge of age of first tooth eruption 
      over M1. Knowledge of recommended age for bottle weaning was higher among D4
      students but not significantly more than  M4 students. CONCLUSION: The majority
      of medical students showed inadequate knowledge indicating that medical 
      curriculum should emphasise on oral health topics of public health relevance like
      ECC and its prevention. Dental students  had better knowledge regarding early
      childhood oral health, but lacked knowledge on its preventive aspects.

PMID- 22455532
TI  - Alveolar bone height in primary dentition a radiographic evaluation related to
      caries lesions.
AB  - AIM: This was to evaluate the CEJ-ABC distance in sound and unsound deciduous
      teeth, according to subject's  age and the presence of caries. MATERIALS AND
      METHODS:  STUDY DESIGN: cross-sectional study. The study sample  comprised 334
      radiographs, the teeth were divided in two groups, according to the interproximal
      surface characteristics. The  distal surface of the mandibular first deciduous
      molar and/or the mesial surface of the second mandibular deciduous molar  were
      analysed. RESULTS: The average for the CEJ-ABC distance in the distal surface of
      the mandibular first molar was  different between sound and carious teeth. The
      same behaviour was observed in the mesial surface of the mandibular second 
      molar. Both the presence of lesion on the interproximal surface and the subject
      age exherted influence over the mean CEJ- ABC distance. No interaction between
      these factors was statistically observed. STATISTICS: data were analyzed with
      SPSS. Two- way ANOVA was used to assess the distance of CEJ-ABC considering the
      interproximal surface status and age. CONCLUSION: Although the observation that
      both the interproximal surface status and the age had influence on the CEJ- ABC
      distance values, in the present study the interaction between these variables was
      not a determinant for the increase CEJ- ABC distances.

PMID- 22455533
TI  - The primary Maxillary Central Incisor in the Solitary Median Maxillary Central
      Incisor syndrome.
AB  - AIM: Solitary Median Maxillary Central Incisor (SMMCI) is a developmental anomaly
      in the permanent dentition  with one single central incisor in the maxilla,
      positioned exactly in the midline. This condition has been associated with  extra
      and intraoral malformations in the frontonasal segment of the cranium and face.
      It is not known whether the centrally  located permanent incisor is always
      preceded by a centrally located primary incisor. The aim was to analyse whether a
      permanent single central incisor in SMMCI is always preceded by a primary single
      central incisor and to study extra- and  intraoral phenotypic traits of the
      condition. MATERIALS AND METHODS:  STUDY DESIGN: cross-sectional radiographic
      study  of 11 children, visual analysis of photos and dental and panoramic
      radiographs. RESULTS: Nine of the 11 cases exhibited a  primary SMMCI with one
      symmetrical crown and root. Two cases exhibited two separate primary central
      incisor crowns with  fused roots. The phenotypical traits (indistinct philtrum,
      lack of normal upper lip contour, missing superior labial frenulum  and distinct
      mid-palatal ridge) were findings observed in young children with a primary SMMCI.
      CONCLUSION: The present  study concludes and stresses the necessity of diagnosing
      of the SMMCI condition early in life. Furthermore, paediatric  dentists are
      recommended to be aware of the condition and to refer these patients to
      interdisciplinary diagnostics and  treatment.

PMID- 22455534
TI  - Structural morphological characteristics and craniofacial development in
      macrocephaly-cutis marmorata  telangiectatica congenita.
AB  - AIM: Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) is a
      craniofacial defect secondary to  macrosomia; a case is presented in order to
      increase knowledge of the related complications in particular with respect to 
      craniofacial development. CASE REPORT: The authors report a case of M-CMTC
      evaluated from the genetic standpoint and  that of craniofacial development. The
      aim was to analyse the patient's clinical development and to plan orthopaedic and
      surgical treatment, focused on detecting and correcting structural and/or
      functional maxillomandibular anomalies that are  likely to worsen over time. As M
      CMTC is a typical morphostructural anomaly found in many patients with
      macrosomia,  increased knowledge of the problem and awareness of the related
      complications appeared useful so as to tackle them  appropriately. Orthopaedic
      treatment partially corrected the asymmetry and reduced the structural
      discrepancy, avoiding or  at least simplifying surgical treatment on completion
      of growth.

PMID- 22455535
TI  - Gingival Myofibroma. A case report.
AB  - AIM: The Myofibroma (MF) is a benign mesenchymal tumor frequently observed in the
      skin and subcutaneous tissue of the head-neck region. It is described mainly in
      infants with congenital forms and, in early childhood, with acquired forms. Less
      often, it can be observed in adolescents and adults. The location of a MF in the
      oral cavity is occasional and differential diagnosis must be established with
      other benign and malignant neoplasms, high or low grade, of the oral mucosa. The
      histology of the myofibroma shows a biphasic growth pattern: elongated spindle
      cells with eosinophilic cytoplasm, in the borders, polygonal cells arranged in a
      palisading pattern, with hyperchromatic nuclei, in the central portions. The
      diagnosis of MF, usually made after excision of the neoformation, is obtained by
      means of immunohistochemistry, in which there is positivity for vimentin and
      alphaactine smooth muscle antibodies and negativity for keratin, S-100, EMA
      (Epithelial Membrane Antigen) antibodies. The treatment is surgical; the
      prognosis is generally good with low rates of recurrence after excision. CASE
      REPORT: The authors describe a case of MF in a 16-year-old male subject, that
      came to their observation for the growth of a considerable mass attached to the
      gingival mucosa, describing the therapeutic strategy.

PMID- 22455536
TI  - Sensitive and homogeneous protein detection based on target-triggered aptamer
      hairpin switch and nicking enzyme assisted fluorescence signal amplification.
AB  - Specific and sensitive detection of proteins in biotechnological applications and
      medical diagnostics is one of the most important goals for the scientific
      community. In this study, a new protein assay is developed on the basis of
      hairpin probe and nicking enzyme assisted signal amplification strategy. The
      metastable state hairpin probe with short loop and long stem is designed to
      contain a protein aptamer for target recognition. A short Black Hole Quencher
      (BHQ)-quenching fluorescence DNA probe (BQF probe) carrying the recognition
      sequence and cleavage site for the nicking enzyme is employed for fluorescence
      detection. Introduction of target protein into the assay leads to the formation
      change of hairpin probe from hairpin shape to open form, thus faciliating the
      hybridization between the hairpin probe and BQF probe. The fluorescence signal is
      amplified through continuous enzyme cleavage. Thrombin is used as model analyte
      in the current proof-of-concept experiments. This method can detect thrombin
      specifically with a detection limit as low as 100 pM. Additionally, the proposed
      protein detection strategy can achieve separation-free measurement, thus
      eliminating the washing steps. Moreover, it is potentially universal because
      hairpin probe can be easily designed for other proteins by changing the
      corresponding aptamer sequence.

PMID- 22455537
TI  - Natural products and colon drug delivery.

PMID- 22455538
TI  - Blastic plasmacytoid dendritic cell neoplasm: a report of four cases and review
      of the literature.
AB  - BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known
      as agranular CD4(+) /CD56(+) haematodermic neoplasm (CD4/CD56 HN), is a rare
      distinct form of lymphoma-like entity known of dermatologists because of its
      marked predilection for cutaneous involvement, and its aggressive behaviour.
      Moreover, the association or the evolution to an acute leukaemia entity that
      still expresses CD4 and CD56 markers is almost systematic. This new described
      entity of 'CD4(+) /CD56(+) leukaemia' or 'leukaemia of plasmacytoid dendritic
      cell lineage' has a poor prognostic and may lead to include haematopoietic stem
      cell transplantation in the treatment strategy as early as possible. REPORT OF
      CASES: We report here four cases presenting with skin lesions and haematological
      signs. One of the patients underwent allogeneic stem cell transplantation, with a
      relapse-free survival of 40 months. We discuss the diagnosis features as well as
      the treatment options. CONCLUSION: A collaborative work between dermatologists
      and onco-haematologists is essential to give patients the best chance of complete
      and long-term response.

PMID- 22455539
TI  - Antimicrobial susceptibility and molecular typing of multiple Chlamydiaceae
      species isolated from genital infection of women in Egypt.
AB  - This study investigated the existence of vaginal Chlamydia infection and the
      prevalence of the disease in symptomatic gynecologically diseased women in Egypt.
      In addition, the antibiotics penicillin, tetracycline, and erythromycin were
      evaluated for their in vitro antichlamydial activity of the isolated strains.
      Vaginal swabs (n=160) were collected from females gynecologically diseased using
      cotton swabs. Samples were tested for Chlamydia by Vero cells tissue culture,
      chicken embryo, Gimenez staining, direct fluorescein-conjugated monoclonal
      antibody staining, and immunoperoxidase. Polymerase chain reaction (PCR) analyses
      conducted for the presence of chlamydial DNA was used to detect its specific DNA
      by the omp2 gene. PCR analyses conducted for the presence of chlamydial DNA
      revealed that 112/160 (70%) were positive for Chlamydiaceae. The specific DNA
      defined by the omp2 gene identified them as Chlamydia trachomatis (17/112,
      15.2%), Chlamydophila psittaci (56/112, 50.0%), and Chlamydophila abortus
      (40/112, 35.7%). The antibiotics penicillin, tetracycline, and erythromycin at
      different concentrations were effective in inactivating the viability of
      Chlamydiaceae isolates.

PMID- 22455540
TI  - Beta-lactam resistance mechanisms in Pseudomonas aeruginosa strains causing
      bloodstream infections: comparative results between Brazilian and American
      isolates.
AB  - This study evaluated the presence of distinct mechanisms of beta-lactam
      resistance in 122 Pseudomonas aeruginosa isolates, causing bloodstream infections
      at Hospital Sao Paulo (HSP, Brazil; 82 isolates) and Virginia Commonwealth
      University Medical Center (VCU, United States; 40 isolates). By Clinical
      Laboratory Standards Institute agar dilution, Brazilian P. aeruginosa isolates
      showed higher resistance rates to most antimicrobials tested than those collected
      from the United States, except for ciprofloxacin. Carbapenem hydrolysis was
      detected in seven P. aeruginosa from HSP, in which bla(SPM-1) (n=5), bla(IMP-1)
      (n=1), and bla(IMP-16) (n=1) were detected by polymerase chain reaction (PCR)
      followed by DNA sequencing. The production of GES-5 was observed in 1.25% of HSP
      isolates. No extended-spectrum beta-lactamase-encoding genes were detected in the
      VCU isolates. Expression of efflux systems genes (mexB, mexD, mexF, and mexY) was
      evaluated by quantitative reverse transcriptase-PCR. In HSP isolates MexXY-OprM
      (41.4%) efflux system was more frequently overexpressed, in contrast to what was
      observed in the VCU isolates, where both MexXY-OprM (25.0%) and MexAB-OprM
      (25.0%) were equally overexpressed. The oprD downregulation was similar among
      isolates collected from the HSP (92.7%) and VCU (95.0%). On the other hand, ampC
      overexpression was observed only among HSP isolates (31.7%). The distinct
      antimicrobial susceptibility profile and mechanisms of beta-lactam resistance
      found among P. aeruginosa isolated from teaching hospitals located in Brazil and
      the United States exemplify the importance of local epidemiology in determining
      antimicrobial resistance rates.

PMID- 22455541
TI  - Caregiving in severe mental illness: the psychometric properties of the
      Involvement Evaluation Questionnaire in Portugal.
AB  - BACKGROUND: Despite the achievements of previous research, caregiving assessments
      in severe mental illness should be crossculturally validated in order to define
      risk groups or to evaluate family work. This study reports on the psychometric
      properties of the European version of the Involvement Evaluation Questionnaire
      (IEQ-EU) in Portugal. METHODS: A Portuguese translation of the IEQ-EU was
      developed according to the 'European Psychiatric Services: Inputs Linked to
      Outcome Domains and Needs' (EPSILON) group guidelines. We then studied 194
      caregivers who were related to patients with schizophrenia spectrum disorders in
      psychiatric outpatient services. All relatives were assessed using the IEQ-EU. In
      order to describe the corresponding patients' sample, the majority (n = 162) was
      evaluated with the World Health Organization Disability Assessment Schedule (WHO
      DAS II); 108 patients were also assessed with the Brief Psychiatric Rating Scale
      (BPRS) and the Global Assessment of Functioning (GAF). RESULTS: The factor
      structure of the Portuguese version of the questionnaire was similar to the
      original; internal consistency was good, with Cronbach's alpha ranging from 0.71
      to 0.87 in the IEQ-EU scales (total score and domains: tension, supervision,
      worrying, urging); test-retest reliability yielded intraclass correlation
      coefficients (ICCs) from 0.80 to 0.94, concerning the same scores. Ecological
      validity was confirmed. Most caregiving consequences were reported on the
      worrying domain of the IEQ-EU. CONCLUSIONS: Validity and reliability of the
      Portuguese IEQ-EU translation were established. Specifically the four IEQ-EU
      subscale domains seem to be valid in Portugal.

PMID- 22455543
TI  - Discovery and structural elucidation of the illegal azo dye Basic Red 46 in sumac
      spice.
AB  - An unknown red dye was discovered in a sumac spice sample during routine analysis
      for Sudan dyes. LC-DAD and LC-MS/MS did not reveal the identity of the red
      substance. Nevertheless, using LC-high-resolution MS and isotope ratio
      comparisons the structure was identified as Basic Red 46. The identity of the dye
      was further confirmed by comparison with a commercial hair-staining product and
      two textile dye formulations containing Basic Red 46. Analogous to the Sudan
      dyes, Basic Red 46 is an azo dye. However, some of the sample clean-up
      methodology utilised for the analysis of Sudan dyes in food prevents its
      successful detection. In contrast to the Sudan dyes, Basic Red 46 is a cation.
      Its cationic properties make it bind strongly to gel permeation columns and
      silica solid-phase extraction cartridges and prevent elution with standard
      eluents. This is the first report of Basic Red 46 in food. The structure
      elucidation of this compound as well as the disadvantages of analytical methods
      focusing on a narrow group of targeted analytes are discussed.

PMID- 22455542
TI  - Bacterial production of organic acids enhances H2O2-dependent iodide oxidation.
AB  - To develop an understanding of the role that microorganisms play in the transport
      of (129)I in soil-water systems, bacteria isolated from subsurface sediments were
      assessed for iodide oxidizing activity. Spent liquid medium from 27/84 bacterial
      cultures enhanced iodide oxidation 2-10 fold in the presence of H(2)O(2). Organic
      acids secreted by the bacteria were found to enhance iodide oxidation by (1)
      lowering the pH of the spent medium, and (2) reacting with H(2)O(2) to form
      peroxy carboxylic acids, which are extremely strong oxidizing agents. H(2)O(2)
      dependent iodide oxidation increased exponentially from 8.4 to 825.9 MUM with
      decreasing pH from 9 to 4. Organic acids with >=2 carboxy groups enhanced
      H(2)O(2)-dependent iodide oxidation (1.5-15-fold) as a function of increasing pH
      above pH 6.0, but had no effect at pH <= 5.0. The results indicate that as pH
      decreases (<=5.0), increasing H(2)O(2) hydrolysis is the driving force behind
      iodide oxidation. However, at pH >= 6.0, spontaneous decomposition of peroxy
      carboxylic acids, generated from H(2)O(2) and organic acids, contributes
      significantly to iodide oxidation. The results reveal an indirect microbial
      mechanism, organic acid secretion coupled to H(2)O(2) production, that could
      enhance iodide oxidation and organo-iodine formation in soils and sediments.

PMID- 22455544
TI  - A model of integrative care for low-back pain.
AB  - OBJECTIVES: While previous studies focused on the effectiveness of individual
      complementary and alternative medical (CAM) therapies, the value of providing
      patients access to an integrated program involving multiple CAM and conventional
      therapies remains unknown. The objective of this study is to explore the
      feasibility and effects of a model of multidisciplinary integrative care for
      subacute low-back pain (LBP) in an academic teaching hospital. DESIGN: This was a
      pilot randomized trial comparing an individualized program of integrative care
      (IC) plus usual care to usual care (UC) alone for adults with LBP. SUBJECTS:
      Twenty (20) individuals with LPB of 3-12 weeks' duration were recruited from an
      occupational health clinic and community health center. INTERVENTIONS:
      Participants were randomized to 12 weeks of individualized IC plus usual care
      versus UC alone. IC was provided by a trained multidisciplinary team offering CAM
      therapies and conventional medical care. OUTCOME MEASURES: The outcome measures
      were symptoms (pain, bothersomeness), functional status (Roland-Morris score), SF
      12, worry, and difficulty performing three self-selected activities. RESULTS:
      Over 12 weeks, participants in the IC group had a median of 12.0 visits (range 5
      25). IC participants experienced significantly greater improvements at 12 weeks
      than those receiving UC alone in symptom bothersomeness (p=0.02) and pain
      (p=0.005), and showed greater improvement in functional status (p=0.08). Rates of
      improvement were greater for patients in IC than UC in functional status
      (p=0.02), bothersomeness (p=0.002), and pain scores (p=0.001). Secondary outcomes
      of self-selected most challenging activity, worry, and the SF-12 also showed
      improvement in the IC group at 12 weeks. These differences persisted at 26 weeks,
      but were no longer statistically significant. CONCLUSIONS: It was feasible for a
      multidisciplinary, outpatient IC team to deliver coordinated, individualized
      intervention to patients with subacute LBP. Results showed a promising trend for
      benefit of treating patients with persistent LBP with this IC model, and warrant
      evaluation in a full-scale study.

PMID- 22455546
TI  - Synthesis, crystal structure, and physical properties of the type-I clathrate
      Ba(8-delta)Ni(x)?(y)Si(46-x-y).
AB  - Type-I clathrate phase Ba(8)Ni(x)?(y)Si(46-x-y) (? = vacancy) was obtained from
      the elements at 1000  degrees C with the homogeneity range 2.4 <= x <= 3.8 and 0
      <= y <= 0.9. In addition, samples with low Ni content (x = 1.4 and 1.6; y = 0)
      and small Ba deficiency were prepared from the melt by steel-quenching.
      Compositions were established by microprobe analysis and crystal structure
      determination. Ba(8-delta)Ni(x)?(y)Si(46-x-y) crystallizes in the space group Pm
      3n (No. 223) with lattice parameter ranging from a = 10.3088(1) A for
      Ba(7.9(1))Ni(1.4(1))Si(44.6(1)) to a = 10.2896(1) A for
      Ba(8.00(3))Ni(3.82(4))Si(41.33(6)). Single-crystal X-ray diffraction data
      together with microprobe analysis indicate an increasing number of framework
      vacancies toward compositions with higher Ni content. For all compositions
      investigated, Ni K-edge X-ray absorption spectroscopy measurements showed an
      electronic state close to that of elemental Ni. All samples exhibit metallic-like
      behavior with moderate thermopower and low thermal conductivity in the
      temperature range 300-773 K. Samples with compositions
      Ba(7.9(1))Ni(1.4(1))Si(44.6(1)) and Ba(7.9(1))Ni(1.6(1))Si(44.4(1)) are
      superconducting with T(c) values of 6.0 and 5.5 K, respectively.

PMID- 22455545
TI  - Characterization of a pneumococcal meningitis mouse model.
AB  - BACKGROUND: S. pneumoniae is the most common causative agent of meningitis, and
      is associated with high morbidity and mortality. We aimed to develop an
      integrated and representative pneumococcal meningitis mouse model resembling the
      human situation. METHODS: Adult mice (C57BL/6) were inoculated in the cisterna
      magna with increasing doses of S. pneumoniae serotype 3 colony forming units
      (CFU; n = 24, 104, 105, 106 and 107 CFU) and survival studies were performed.
      Cerebrospinal fluid (CSF), brain, blood, spleen, and lungs were collected.
      Subsequently, mice were inoculated with 104 CFU S. pneumoniae serotype 3 and
      sacrificed at 6 (n = 6) and 30 hours (n = 6). Outcome parameters were bacterial
      outgrowth, clinical score, and cytokine and chemokine levels (using Luminex(r))
      in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration,
      parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal
      apoptosis were assessed in histopathological studies. RESULTS: Lower doses of
      bacteria delayed onset of illness and time of death (median survival CFU 104, 56
      hrs; 105, 38 hrs, 106, 28 hrs. 107, 24 hrs). Bacterial titers in brain and CSF
      were similar in all mice at the end-stage of disease independent of inoculation
      dose, though bacterial outgrowth in the systemic compartment was less at lower
      inoculation doses. At 30 hours after inoculation with 104 CFU of S. pneumoniae,
      blood levels of KC, IL6, MIP-2 and IFN- gamma were elevated, as were brain
      homogenate levels of KC, MIP-2, IL-6, IL-1beta and RANTES. Brain histology
      uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration,
      microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and
      subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6
      and 30 hours, respectively. CONCLUSION: We have developed and validated a murine
      model of pneumococcal meningitis.

PMID- 22455547
TI  - Effects of handicraft sitting postures on lower trunk muscle fatigue.
AB  - The purpose of this study was to assess trunk muscle fatigue in seated handicraft
      tasks using surface electromyography (sEMG) and visual analogue scale (VAS)
      ratings for trunk discomfort, and to assess the relationship of these responses.
      Twenty-three participants were randomly assigned to assumed crossed-leg and heel
      sitting postures for 30 min. Normalised median frequency (NMF) slopes for lumbar
      multifidus (LM) and internal oblique (IO) muscles and VAS ratings were recorded.
      Results revealed that the crossed-leg posture produced significantly steeper NMF
      slopes for both sides of the LM and IO muscles than heel sitting. Greater VAS
      ratings were found in crossed-leg sitting posture than the heel sitting posture.
      The NMF slopes and the VAS ratings had significant negative correlations for both
      postures. Findings support heel sitting in handicraft tasks over crossed-leg
      sitting due to greater trunk muscle fatigue and discomfort during the latter
      posture. Results support VAS ratings as a complementary method to sEMG for
      identifying trunk muscle fatigue.    Practitioner Summary: Trunk muscle fatigue
      in handicraft work is a potential risk for low back pain. Based on EMG and
      discomfort analyses, heel sitting is preferred to crossed-leg posture. Discomfort
      ratings are consistent with EMG measures in identifying trunk muscle fatigue in
      such postures.

PMID- 22455548
TI  - Portable and quantitative detection of protein biomarkers and small molecular
      toxins using antibodies and ubiquitous personal glucose meters.
AB  - Developing portable and low-cost methods for quantitative detection of large
      protein biomarkers and small molecular toxins can play a significant role in
      controlling and preventing diseases or toxins outbreaks. Despite years of
      research, most current methods still require laboratory-based or customized
      devices that are not widely available to the general public for quantitative
      analysis. We have previously demonstrated the use of personal glucose meters
      (PGMs) and functional DNAs for the detection of many nonglucose targets. However,
      the range of targets detectable by functional DNAs is limited at the current
      stage. To expand the range of targets that can be detected by PGMs, we report
      here the use of antibodies in combination with sandwich and competitive assays
      for quantitative detection of protein biomarkers (PSA, with a detection limit of
      0.4 ng/mL) and small molecular toxins (Ochratoxin A, with a detection limit of
      6.8 ng/mL), respectively. In both assay methods, with invertase conjugates as the
      link, quantitative detection is achieved via the dependence between the
      concentrations of the targets in the sample and the glucose measured by PGMs.
      Given the wide availability of antibodies for numerous targets, the methods
      demonstrated here can expand the range of target detection by PGMs significantly.

PMID- 22455549
TI  - Long-term clinical evaluation of a 800-nm long-pulsed diode laser with a large
      spot size and vacuum-assisted suction for hair removal.
AB  - BACKGROUND: The long-pulsed diode (800-810-nm) laser is one of the most commonly
      used and effective lasers for hair removal. Limitations of currently available
      devices include a small treatment spot size, treatment-associated pain, and the
      need for skin cooling. OBJECTIVE: To evaluate the long-term hair reduction
      capabilities of a long-pulsed diode laser with a large spot size and vacuum
      assisted suction. METHODS: Thirty-five subjects were enrolled in a prospective,
      self-controlled, single-center study of axillary hair removal. The study
      consisted of three treatments using a long-pulsed diode laser with a large spot
      size and vacuum-assisted suction at 4- to 6-week intervals with follow-up visits
      6 and 15 months after the last treatment. Hair clearance was quantified using
      macro hair-count photographs taken at baseline and at 6- and 15-month follow-up
      visits. Changes in hair thickness and color, levels of treatment-associated pain,
      and adverse events were additional study endpoints. RESULTS: There was
      statistically significant hair clearance at the 6 (54%) and 15-month (42%) follow
      up visits. Remaining hairs were thinner and lighter at the 15-month follow-up
      visit, and the majority of subjects reported feeling up to mild to moderate pain
      during treatment without the use of pretreatment anesthesia or skin cooling.
      CONCLUSIONS: A long-pulsed diode laser with a large spot size and vacuum-assisted
      suction is safe and effective for long-term hair removal. This is the largest
      prospective study to evaluate long-term hair removal and the first to quantify
      decreases in hair thickness and darkness with treatment.

PMID- 22455550
TI  - Mutations in Streptococcus pneumoniae penicillin-binding protein 2x: importance
      of the C-terminal penicillin-binding protein and serine/threonine kinase
      associated domains for beta-lactam binding.
AB  - Penicillin-binding protein 2x (PBP2x) mutations that occur during the selection
      with beta-lactams are located within the central penicillin
      binding/transpeptidase (TP) domain, and are believed to mediate resistance by
      interfering with the formation of a covalent complex of the active site serine
      with the antibiotic. We now investigated the effect of two point mutations found
      in two independently obtained laboratory mutants that are located at the surface
      of the TP domain with their side chains facing outside (G422D respectively
      R426C). They have no significant effect on resistance to cefotaxime in vivo or on
      binding to BocillinTMFL to the active site in vitro using purified PBP2x
      derivatives, thus apparently do not affect the active site directly. In contrast,
      in silico modeling revealed that they affect van der Waal's interactions with the
      PASTA1 (PBP and serine/threonine kinase associated) domain of the C-terminal
      extension and a noncovalent cefuroxime molecule found in the X-ray structure of
      an acylated PBP2x, suggesting some effect of the mutations on the interaction of
      the TP domain with PASTA1 and/or with the antibiotic associated with PASTA1. The
      effect of the PASTA domains on covalent binding of PBP2x to Bocillin FL was then
      investigated using a series of soluble truncated PBP2x derivatives. Deletion of
      127 C-terminal residues, that is, of both PASTA domains, decreased binding
      dramatically by ~90%. Surprisingly, deletion of only 40 amino acids resulted in
      the same phenotype, whereas the absence of 30 amino acids affected binding
      marginally by 10%, documenting a crucial role of the C-terminal domain for beta
      lactam binding.

PMID- 22455551
TI  - Graphene, carbon nanotubes and nanoparticles in cell metabolism.
AB  - Nanomaterials and nanotechnology is in forefront of materials research. Minimal
      attention is given to the potential participation of these materials in cell
      metabolism. Here we review recent efforts to understanding how carbon
      nanomaterials participate on cell metabolism. First, the introduction to the
      materials science of graphene, carbon nanotubes and metallic nanoparticles is
      given. Second, different mechanisms of participation of these materials on the
      cell metabolism are discussed and elucidated.

PMID- 22455552
TI  - Long-term exposure to cadmium in food and cigarette smoke, liver effects and
      hepatocellular carcinoma.
AB  - Rising incidence of hepatocellular carcinoma (HCC) has been noted in recent years
      along with diabetes for which reasons and mechanisms are unclear. The rise in HCC
      is attributed to increasing rates of hepatitis C virus (HCV) infections while
      increases in diabetes are attributed to obesity. Increased HCC risk has also been
      noted in diabetes and obesity. Cadmium, a common food contaminant and a
      constituent of cigarette smoke, is one of ten chemicals considered by the World
      Health Organization to be of major public health concern. A correlation of
      cadmium intakes and increased HCC mortality risk has been noted in an ecological
      study while both hepatocellular carcinoma and hepatic adenoma occurred in cadmium
      exposed mice. In the U.S. NHANES III, urinary cadmium levels, indicative of long
      term exposure, have been associated with pre-diabetes and diabetes in a dose
      dependent manner. Intriguing possibility is that cadmium may increase HCC risk
      through increasing the frequency of hepatogenous diabetes. Overall aim of the
      present review is to explore if cadmium is a relevant risk factor in chronic
      liver disease and a rising HCC incidence. It will highlight cadmium levels
      detectable in various foods, livers, kidneys and urine samples of humans together
      with global health threat of ingested cadmium, pointing to measures for reducing
      exposure and a need for revision of guidelines for safe intake levels. Lastly, it
      will examine evidence for potential roles of cadmium in chronic liver diseases
      and HCC risk in a call for human case-control studies and animal experiments to
      elucidate underlying molecular mechanisms.

PMID- 22455553
TI  - Molecular and cellular mechanisms of hexavalent chromium-induced lung cancer: an
      updated perspective.
AB  - For over a century, chromium (Cr) has found widespread industrial and commercial
      use, namely as a pigment, in the production of stainless steel and in chrome
      plating. The adverse health effects to the skin and respiratory tract of
      prolonged exposure to Cr have been known or suspected for a long time, but it was
      much more recently that the toxicity of this element was unequivocally attributed
      to its hexavalent state. Based on the combined results of extensive
      epidemiological studies, animal carcinogenicity studies and several types of
      other relevant data, authoritative regulatory agencies have found sufficient
      evidence to classify hexavalent chromium [Cr(VI)] compounds as encountered in the
      chromate production, chromate pigment production and chromium plating industries
      as carcinogenic to humans. Crucial for the development of novel strategies to
      prevent, detect and/or treat Cr(VI)-induced cancers is a detailed knowledge of
      the molecular and cellular mechanisms underlying these pathologies.
      Unfortunately, in spite of a considerable research effort, crucial facets of
      these mechanisms remain essentially unknown. This review is intended to provide a
      concise, integrated and critical perspective of the current state of knowledge
      concerning multiple aspects of Cr(VI) carcinogenesis. It will present recent
      theories of Cr(VI)-induced carcinogenesis and will include aspects not
      traditionally covered in other reviews, such as the possible involvement of the
      energy metabolism in this process. A brief discussion on the models that have
      been used in the studies of Cr(VI)-induced carcinogenicity will also be included,
      due to the impact of this parameter on the relevance of the results obtained.

PMID- 22455554
TI  - From amino acids to proteins as targets for metal-based drugs.
AB  - Metallomics and metalloproteomics are emerging fields addressing the role,
      uptake, transport and storage of trace metals ions both toxic and essential for
      an organism. Research areas related to the understanding of the mechanisms of
      life processes associated to metals are covered. Similarly to the genome and
      proteome terms, metallome was introduced to refer to metalloproteins,
      metalloenzymes and other metal-containing biomolecules in a biological system.
      This review aims to give an overview of metal ions behaviour in organisms. The
      interactions of metals with biomolecules such as amino acids, peptides and
      protein are the main focus. Special attention is paid to the application of
      nanotechnology-based techniques using these interactions for medical purposes
      such as diagnostics, imaging and therapy.

PMID- 22455555
TI  - Aspartate aminotransferase: bridging carbohydrate and energy metabolism in
      Plasmodium falciparum.
AB  - In this mini-review we briefly examine and summarize evidence on the role of the
      plasmodial aspartate aminotransferase (AspAT) of the malarial parasite. Recent
      data have provided information on the products of the purine salvage pathway as
      well as the glycolytic and oxidative phosphorylation pathways, suggesting that
      the reaction catalyzed by AspAT is an essential step in all these biochemical
      processes. While the biological role of the oxidative phosphorylation cycle still
      remains to be demonstrated, the presence of a single protein that is functional
      in multiple pathways (i.e. amino acid/purine/pyrimidine biosynthesis and
      carbohydrate metabolism) provides a high potential for the development of novel
      strategies to combat the spread of multi-drug resistant malaria.

PMID- 22455556
TI  - Biomechanical evaluation of supermarket cashiers before and after a redesign of
      the checkout counter.
AB  - An experiment was carried out on supermarket cashiers to evaluate the time,
      kinematic and electromyographic changes, in both sitting and standing positions,
      following the redesign of a checkout counter. The novelty of the prototype
      checkout counter is a disk wheel placed in the bagging area, which is designed to
      avoid the cashier having to manually push products along the bagging area. The
      kinematic evaluation was based on the upper limb and trunk range of motions
      (RoM). The electromyographic parameters assessed were mean and maximum muscular
      activations. Three factors were taken into account: design (before and after
      redesign), posture (standing or sitting) and bagging area (anterior or
      posterior). The results show that the RoM values are lowest after the
      intervention and in the standing position. Mean and maximum muscular activation
      patterns are similar. Differences related to the bagging area in which the goods
      were released also emerged. The disk wheel represents a valid aid for reducing
      biomechanical overload in cashiers; the standing position is biomechanically more
      advantageous.    Practitioner Summary: EMG and optoelectronic motion analysis
      systems are useful for the quantitative assessment of the effects of the redesign
      of the workplace biomechanical risk. Our results suggest that a disk wheel
      positioned in the bagging area reduces the biomechanical risk for cashiers and
      increases time spent resting.

PMID- 22455557
TI  - Hydroxy-amide functionalized azolium salts for Cu-catalyzed asymmetric conjugate
      addition: stereocontrol based on ligand structure and copper precatalyst.
AB  - A series of hydroxy-amide functionalized azolium salts have been designed and
      synthesized for Cu-catalyzed asymmetric conjugate addition reaction. The
      (CH(2))(2)-bridged hydroxy-amide functionalized azolium ligand precursors 2, in
      addition to the previously reported CH(2)-bridged azolium salts 1, have been
      prepared from readily available enantiopure beta-amino alcohols. The combination
      of a Cu species with 1 or 2 efficiently promoted the 1,4-addition reaction of
      cyclic enones with dialkylzincs. For example, the reaction of 2-cyclohepten-1-one
      (17) with Bu(2)Zn in the presence of catalytic amounts of Cu(OTf)(2) and 1 gave
      (S)-3-butylcycloheptanone (20) in 99% yield and 96% ee. On the other hand, when
      the reaction was carried out under the influence of Cu(OTf)(2) combined with 2,
      (R)-20 in preference to (S)-20 was obtained in 98% yield and 80% ee. In this
      manner, the enantioselecvity was switched by controlling the structure of chiral
      ligand. Additionally, the reversal of enantioselectivity was also achieved by
      changing the Cu precatalyst from Cu(OTf)(2) to Cu(acac)(2) with the same ligand.
      The combination of Cu(acac)(2) with CH(2)-bridged azolium salt 1 in the reaction
      of 17 with Bu(2)Zn led to formation of (R)-20 as a major product in 55% yield and
      80% ee. This result was in contrast to the Cu(OTf)(2)/1 catalytic system, where
      the 1,4-adduct with opposite configuration was obtained. Moreover, use of the
      Cu(acac)(2)/2 catalytic system produced (S)-20, while (R)-20 was formed by the
      Cu(OTf)(2)/2 catalytic system. Thus, it was found that either varying the linker
      of the chiral ligands or changing the counterion of Cu species between a OTf and
      acac ligand initially on the metal led to dual enantioselective control in the
      1,4-addition reaction.

PMID- 22455558
TI  - Trends in missed presentations and late HIV diagnosis in a UK teaching hospital:
      a retrospective comparative cohort study.
AB  - BACKGROUND: Late diagnosis is an important cause of HIV-related morbidity,
      mortality and healthcare costs in the UK and undiagnosed infection limits efforts
      to reduce transmission. National guidelines provide recommendations to increase
      HIV testing in all healthcare settings. We evaluated progress towards these
      recommendations by comparing missed opportunities for HIV testing and late
      diagnosis in two six year cohorts from North East Scotland. METHODS: We reviewed
      diagnostic pathways of all patients newly diagnosed with HIV referred to
      infectious diseases and genito-urinary medicine services between 1995 and 2000
      (n=48) and 2004 to 2009 (n=117). Missed presentations (failure to diagnose<=1
      month of a clinical or non-clinical indicator for testing), late diagnosis
      (CD4<350 cells/mm3), and time to diagnosis (months from first presentation to
      diagnosis) were compared between cohorts using chi2 and log-rank tests.
      Determinants of missed presentation were explored by multivariate logistic
      regression. Breslow-Day tests assessed change in diagnostic performance by
      patient subgroup. RESULTS: There were significant decreases in missed
      presentations (33% to 17%; P=0.02) and time to diagnosis (mean 17 months to 4
      months; P=0.005) but not in late diagnosis (56% vs. 60%; P=0.57) between earlier
      and later cohorts. In the later cohort patients were significantly more likely to
      have acquired HIV abroad and presented with early HIV disease, and testing was
      more likely to be indicated by transmission risk or contact with GUM services
      than by clinical presentation. Missed presentation remained significantly less
      likely in the later cohort (OR=0.28, 95% CI 0.11 to 0.72; P=0.008) after
      adjustment for age, transmission risks and number of clinical indicators.
      Reductions in missed presentation were greater in patients<40 years, of non-UK
      origin, living in least deprived neighbourhoods and with early disease at
      presentation (P<0.05). 27% of missed presentations occurred in primary care and
      46% in general secondary care. CONCLUSIONS: While early diagnosis has improved in
      epidemiological risk groups, clinical indications for HIV testing continue to be
      missed, particularly in patients who are older, of UK origin and from more
      deprived communities. Increasing testing in non-specialist services is a
      priority.

PMID- 22455559
TI  - Validation of a commercial receptor kit Sulfasensor Honey for the screening of
      sulfonamides in honey according to Commission Decision 2002/657/EC.
AB  - The Sulfasensor Honey kit is a receptor test dedicated to the screening of
      sulphonamide residues respectively in different matrices. The aim of this project
      was to evaluate and validate this kit according to the Community Reference
      Laboratory (CRL) guideline for the validation of screening methods to achieve the
      French control plan for honey. The test is robust, quick (90 min for 40 samples),
      easy to perform and easy to read. The false-positive rate was estimated to be
      12.5%. The detection capabilities CCbeta of the kit were lower than or equal to
      25 ug kg(-1) for sulfamethazine, sulfamerazine, sulfathiazole and sulfapyridine,
      and between 25 and 50 ug kg(-1) for sulfadiazine and sulfadimethoxine, 150 ug kg(
      1) for sulfaquinoxaline, and 1000 ug kg(-1) for sulfamethoxazole and
      sulfamethizole. Sulfanilamide was not detected by the kit. The kit was applicable
      to a wide variety of honeys (different floral and geographical origins, liquid or
      solid). This kit was used to implement the French control plan for the detection
      of antibiotic residues in honey in 2010 in parallel with an HPLC method. However,
      in 2011 the kit was replaced by an LC-MS/MS method for the screening and
      confirmation of sulfonamide residues in honey, which detects all the sulfonamides
      of interest.

PMID- 22455560
TI  - Occurrence and potential sources of pyrethroid insecticides in stream sediments
      from seven U.S. metropolitan areas.
AB  - A nationally consistent approach was used to assess the occurrence and potential
      sources of pyrethroid insecticides in stream bed sediments from seven
      metropolitan areas across the United States. One or more pyrethroids were
      detected in almost half of the samples, with bifenthrin detected the most
      frequently (41%) and in each metropolitan area. Cyhalothrin, cypermethrin,
      permethrin, and resmethrin were detected much less frequently. Pyrethroid
      concentrations and Hyalella azteca mortality in 28-d tests were lower than in
      most urban stream studies. Log-transformed total pyrethroid toxic units (TUs)
      were significantly correlated with survival and bifenthrin was likely responsible
      for the majority of the observed toxicity. Sampling sites spanned a wide range of
      urbanization and log-transformed total pyrethroid concentrations were
      significantly correlated with urban land use. Dallas/Fort Worth had the highest
      pyrethroid detection frequency (89%), the greatest number of pyrethroids (4), and
      some of the highest concentrations. Salt Lake City had a similar percentage of
      detections but only bifenthrin was detected and at lower concentrations. The
      variation in pyrethroid concentrations among metropolitan areas suggests regional
      differences in pyrethroid use and transport processes. This study shows that
      pyrethroids commonly occur in urban stream sediments and may be contributing to
      sediment toxicity across the country.

PMID- 22455561
TI  - Disconnection enhances the second harmonic generation response: synthesis and
      characterization of Ba23Ga8Sb2S38.
AB  - An unusual zero-dimensional quaternary sulfide, Ba(23)Ga(8)Sb(2)S(38), that
      crystallizes in the noncentrosymmetric polar space group Cmc2(1) was discovered
      by solid-state reaction of an elemental mixture. The involvement of a second
      building unit consisting of SbS(3) pyramid and constituting 20% of the structure
      helped to realize the disconnection of the asymmetric GaS(4) tetrahedra. Such a
      disconnection leads to the strongest powder second harmonic generation intensity
      in the IR region among sulfides to date, ~22 times that of commercial AgGaS(2) at
      an incident laser wavelength of 2.05 MUm with the same particle size of 46-74
      MUm.

PMID- 22455562
TI  - Probing electrostatic potential by NMR with the use of a paramagnetic
      lanthanide(III) chelate.
AB  - The paramagnetic complex [Yb(DOTA)](-) forms ion pairs in aqueous solution with
      cationic species such as N-monoalkyl- and N,N'-dialkyl-4,4'-bipyridinium cations.
      The magnitude and sign of the induced (1)H NMR pseudocontact shift values can be
      correlated to the electrostatic potential calculated at the MPWLYP/6-311G**
      level.

PMID- 22455564
TI  - Effect of exercise training on inflammation status among people with metabolic
      syndrome.
AB  - BACKGROUND: Metabolic syndrome is associated with chronic low-grade inflammation,
      a condition thought to play a key role in the pathogenesis of the syndrome. Among
      a number of proinflammatory cytokines, interleukin-18 (IL-18) seems to be the
      best marker for inflammation among people with metabolic syndrome. The aim of
      this study was to examine the effect of aerobic training versus strength training
      on circulating IL-18 and other proinflammatory markers in people with metabolic
      syndrome. METHODS: Thirty-one inactive men and women with metabolic syndrome were
      randomized to either high-intensity aerobic interval training (AIT, n=11),
      strength training (ST, n=10), or a control group (n=10). Exercise training was
      carried out three times per week for 12 weeks. Serum insulin, high-sensitivity C
      reactive protein (hsCRP), IL-18, IL-6, and tumor necrosis factor-alpha (TNF
      alpha) were measured before and after the intervention. RESULTS: Serum IL-18 was
      reduced by 43% after AIT (P<0.001). Although there was no change in TNF-alpha
      from baseline after AIT, the levels were lower compared to the ST (P=0.032) and
      control groups (P=0.039) after the intervention. Total body fat was reduced after
      AIT (from 33.9 +/- 7.3% to 32.2 +/- 7.9%, P<0.001) and ST (from 31.2 +/- 3.9% to
      29.7 +/- 3.4%, P=0.025). There were no changes in serum IL-6, insulin, or hsCRP
      within or between the groups. CONCLUSION: Both ST and AIT reduced fat mass.
      However, only the latter intervention was associated with a more favorable
      inflammatory status among people with metabolic syndrome. CLINICAL TRIAL
      REGISTRATION INFORMATION: http://clinicaltrials.gov/show/NCT00986024/ .

PMID- 22455563
TI  - The expression patterns and correlations of claudin-6, methy-CpG binding protein
      2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl
      histone H4 and their clinicopathological significance in breast invasive ductal
      carcinomas.
AB  - BACKGROUND: Claudin-6 is a candidate tumor suppressor gene in breast cancer, and
      has been shown to be regulated by DNA methylation and histone modification in
      breast cancer lines. However, the expression of claudin-6 in breast invasive
      ductal carcinomas and correlation with clinical behavior or expression of other
      markers is unclear. We considered that the expression pattern of claudin-6 might
      be related to the expression of DNA methylation associated proteins (methyl-CpG
      binding protein 2 (MeCP2) and DNA methyltransferase 1 (DNMT1)) and histone
      modification associated proteins (histone deacetylase 1 (HDAC1), acetyl-histone
      H3 (H3Ac) and acetyl- histone H4 (H4Ac)). METHODS: We have investigated the
      expression of claudin-6, MeCP2, HDAC1, H3Ac and H4Ac in 100 breast invasive
      ductal carcinoma tissues and 22 mammary gland fibroadenoma tissues using
      immunohistochemistry. RESULTS: Claudin-6 protein expression was reduced in breast
      invasive ductal carcinomas (P < 0.001). In contrast, expression of MeCP2 (P <
      0.001), DNMT1 (P = 0.001), HDAC1 (P < 0.001) and H3Ac (P = 0.004) expressions was
      increased. Claudin-6 expression was inversely correlated with lymph node
      metastasis (P = 0.021). Increased expression of HDAC1 was correlated with
      histological grade (P < 0.001), age (P = 0.004), clinical stage (P = 0.007) and
      lymph node metastasis (P = 0.001). H3Ac expression was associated with tumor size
      (P = 0.044) and clinical stage of cancers (P = 0.034). MeCP2, DNMT1 and H4Ac
      expression levels did not correlate with any of the tested clinicopathological
      parameters (P > 0.05). We identified a positive correlation between MeCP2 protein
      expression and H3Ac and H4Ac protein expression. CONCLUSIONS: Our results show
      that claudin-6 protein is significantly down-regulated in breast invasive ductal
      carcinomas and is an important correlate with lymphatic metastasis, but claudin-6
      down-regulation was not correlated with upregulation of the methylation
      associated proteins (MeCP2, DNMT1) or histone modification associated proteins
      (HDAC1, H3Ac, H4Ac). Interestingly, the expression of MeCP2 was positively
      correlated with the expression of H3Ac and H3Ac protein expression was positively
      correlated with the expression of H4Ac in breast invasive ductal carcinoma
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/4549669866581452.

PMID- 22455565
TI  - Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair
      growth.
AB  - BACKGROUND: Recently, autologous platelet-rich plasma (PRP) has attracted
      attention in various medical fields, including plastic and orthopedic surgery and
      dermatology, for its ability to promote wound healing. PRP has been tested during
      facelift and hair transplantation to reduce swelling and pain and to increase
      hair density. OBJECTIVE: To investigate the effects of PRP on hair growth using
      in vivo and in vitro models. METHODS: PRP was prepared using the double-spin
      method and applied to dermal papilla (DP) cells. The proliferative effect of
      activated PRP on DP cells was measured. To understand the mechanisms of activated
      PRP on hair growth, we evaluated signaling pathways. In an in vivo study, mice
      received subcutaneous injections of activated PRP, and their results were
      compared with control mice. RESULTS: Activated PRP increased the proliferation of
      DP cells and stimulated extracellular signal-regulated kinase (ERK) and Akt
      signaling. Fibroblast growth factor 7 (FGF-7) and beta-catenin, which are potent
      stimuli for hair growth, were upregulated in DP cells. The injection of mice with
      activated PRP induced faster telogen-to-anagen transition than was seen on
      control mice. CONCLUSIONS: Although few studies tested the effects of activated
      PRP on hair growth, this research provides support for possible clinical
      application of autologous PRP and its secretory factors for promotion of hair
      growth.

PMID- 22455566
TI  - Thresholds for the effects of pesticides on invertebrate communities and leaf
      breakdown in stream ecosystems.
AB  - We compiled data from eight field studies conducted between 1998 and 2010 in
      Europe, Siberia, and Australia to derive thresholds for the effects of pesticides
      on macroinvertebrate communities and the ecosystem function leaf breakdown. Dose
      response models for the relationship of pesticide toxicity with the abundance of
      sensitive macroinvertebrate taxa showed significant differences to reference
      sites at 1/1000 to 1/10,000 of the median acute effect concentration (EC50) for
      Daphnia magna, depending on the model specification and whether forested upstream
      sections were present. Hence, the analysis revealed effects well below the
      threshold of 1/100 of the EC50 for D. magna incorporated in the European Union
      Uniform Principles (UP) for registration of single pesticides. Moreover, the
      abundances of sensitive macroinvertebrates in the communities were reduced by 27%
      to 61% at concentrations related to 1/100 of the EC50 for D. magna. The
      invertebrate leaf breakdown rate was positively linearly related to the abundance
      of pesticide-sensitive macroinvertebrate species in the communities, though only
      for two of the three countries examined. We argue that the low effect thresholds
      observed were not mainly because of an underestimation of field exposure or
      confounding factors. From the results gathered we derive that the UP threshold
      for single pesticides based on D. magna is not protective for field communities
      subject to multiple stressors, pesticide mixtures, and repeated exposures and
      that risk mitigation measures, such as forested landscape patches, can alleviate
      effects of pesticides.

PMID- 22455567
TI  - High-throughput analysis of protein-protein interactions in picoliter-volume
      droplets using fluorescence polarization.
AB  - Droplet-based microfluidic systems have emerged as a powerful platform for
      performing high-throughput biological experimentation. In addition, fluorescence
      polarization has been shown to be effective in reporting a diversity of
      bimolecular events such as protein-protein, DNA-protein, DNA-DNA, receptor
      ligand, enzyme-substrate, and protein-drug interactions. Herein, we report the
      use of fluorescence polarization for high-throughput protein-protein interaction
      analysis in a droplet-based microfluidic system. To demonstrate the efficacy of
      the approach, we investigate the interaction between angiogenin (ANG) and
      antiangiogenin antibody (anti-ANG Ab) and demonstrate the efficient extraction of
      dissociation constants (K(D) = 10.4 +/- 3.3 nM) within short time periods.

PMID- 22455569
TI  - Comparative study of the antibacterial penetrating effects of wound dressings.
AB  - In an infected wound, bacteria are present not only on the surface but also
      within the granulation tissue. The presence of bacteria inside the granulation
      tissue is one of the reasons for our inability to control infection. We have
      developed an in vitro model of an infected wound using Luria-Bertani (LB) agar
      media and non-pathogenic Escherichia coli, and compared the differences in the
      antibacterial effects of various types of antibacterial wound dressings. The
      results have shown that the penetrating antibacterial effects differed according
      to the type of wound dressing selected. As the thickness of the layer of the LB
      agar media increased, the potency of antibacterial effects caused by penetration
      decreased. In conclusion, it was suggested that antibacterial wound dressings can
      have antibacterial effects against bacteria not only on the surface of an
      infected wound but inside, so it is necessary to use different wound dressings
      according to the conditions of each infected wound.

PMID- 22455570
TI  - Anatomical study of medial and lateral sural cutaneous nerve: implications for
      innervated distally-based superficial sural artery flap.
AB  - We report about reconstruction of the foot with an innervated distally-based
      superficial sural artery flap using the lateral sural cutaneous nerve. The
      sensation of the lateral part of the leg depends on the sural nerve (SN), and the
      medial part of the leg on the saphenous nerve. The border of the area between the
      SN and the saphenous nerve, however, is not clear. To elucidate the distribution
      of the medial and lateral sural cutaneous nerves, the origin, diameter, course,
      branches, and distributions were recorded in 40 adult cadaver lower legs. The
      medial and lateral nerves in all legs (n = 40) were identifiable. In one leg, the
      SN was a direct continuation of the medial branch, and the lateral branch ended
      in the middle of the lower leg. Thick (>1 mm) sub-branches from the lateral
      branch were identified in 26 legs. Most cutaneous branches from it ended in the
      middle of the sural area. We applied the innervated distally-based sural artery
      flap using the lateral branch in 2 cases and obtained good recovery of sensation.
      The lateral branch supplies most of the central sural area and is required for
      the innervation of the distally-based superficial sural artery flap.

PMID- 22455571
TI  - Psychosocial effects of cleft lip and palate on Nigerians: the Ikeja-Lagos
      experience.
AB  - We studied 116 patients who presented with cleft lip and palate (CLP) and were
      seen during a state-wide screening exercise for people with orofacial deformities
      in Ikeja-Lagos, Nigeria between May 2006 and July 2007. Detailed histories were
      taken and physical examinations made. The following psychometric instruments:
      General Health Questionnaire 28 (GHQ28), State-Trait Anxiety Inventory Y1 (STAI
      Y1), STAI-Y2, and Self rating Depression Scale (SDS) were given on the
      respondents by a clinical psychologist. The respondents comprised 57 men and 59
      women with a male:female ratio of 1:1.04. There were 42 (36%) adults and 74 (64%)
      children. Fifty-four (47%) patients had cleft lip (CL), 27 (23%) had cleft lip
      and palate (CLP), and 35 (30%) had cleft palate alone. Forty-five (39%) of the
      respondents were parents and guardians who responded to the presence of the
      deformity on behalf of children who were less than 6 years old, and assessed the
      reactions of those who were aged 6-12 years old. Older patients replied directly
      to the psychometric instruments. The outcome of the assessment of the Mental
      Health Profile of the participants showed high incidence of anxiety, depression,
      and impairment of general wellbeing. The effects were most pronounced in the 6-12
      year age group. We recommend that the psychosocial impacts of CLP on the
      patients, parents, and relations should be managed together with the
      reconstructive procedures.

PMID- 22455572
TI  - Fascicular constrictions in patients with spontaneous palsy of the anterior
      interosseous nerve and the posterior interosseous nerve.
AB  - There is no definition for fascicular constrictions of the spontaneous anterior
      interosseous nerve palsy (sAINP) and spontaneous posterior interosseous nerve
      palsy (sPINP). One surgeon has evaluated his findings in our 32 patients of
      sAINP/sPINP using either photographs or video tapes and proposed a definition.
      All patients had interfascicular neurolysis, and 87 case reports of "fascicular
      constriction" were also evaluated. Fascicular constriction was defined as every
      instance of thinning in the fascicle regardless to its extent. Thinning as a
      result of extrinsic compression was excluded. The fascicular constrictions were
      divided into four types: recessed, recessed-bulging, rotation, and rotation
      bulging constriction. Two independent surgeons went through our findings to
      verify their repeatability. The relation between the fascicular constrictions and
      age at the onset of palsy was evaluated using Student's t test. We found 54
      fascicular constrictions, with many variations. However, they could all be
      categorised by our method. The repeatability among the independent authors was
      96%. The age at the onset of palsy was significantly younger in rotation-bulging
      than in rotation constriction (p = 0.0003). Our definition of describing
      fascicular constrictions was accurate, and should help to provide consensus in
      describing these palsies.

PMID- 22455573
TI  - Comparison of hemihypoglossal-facial nerve transposition with a cross-facial
      nerve graft and muscle transplant for the rehabilitation of facial paralysis
      using the facial clima method.
AB  - To compare quantitatively the results obtained after hemihypoglossal nerve
      transposition and microvascular gracilis transfer associated with a cross facial
      nerve graft (CFNG) for reanimation of a paralysed face, 66 patients underwent
      hemihypoglossal transposition (n = 25) or microvascular gracilis transfer and
      CFNG (n = 41). The commissural displacement (CD) and commissural contraction
      velocity (CCV) in the two groups were compared using the system known as Facial
      clima. There was no inter-group variability between the groups (p > 0.10) in
      either variable. However, intra-group variability was detected between the
      affected and healthy side in the transposition group (p = 0.036 and p = 0.017,
      respectively). The transfer group had greater symmetry in displacement of the
      commissure (CD) and commissural contraction velocity (CCV) than the transposition
      group and patients were more satisfied. However, the transposition group had
      correct symmetry at rest but more asymmetry of CCV and CD when smiling.

PMID- 22455574
TI  - Reconstruction of soft tissue defects in the extremities with a pedicled
      perforator flap: series of 25 patients.
AB  - Since the introduction of perforator-based flaps, new flaps have been described
      for reconstruction of soft tissue defects in the extremities. Pedicled perforator
      flaps, often called propeller flaps, are based on a single perforator and are
      local axial flaps that can be rotated up to 180(0) with the single perforator as
      the pivotal point. Pedicle perforator flaps have gained popularity because they
      have a shorter operating time than free flaps. However, some concern has been
      raised about their reliability. Here we report our results of 11 soft tissue
      reconstructions in the lower leg and 14 in the upper extremity. The defects were
      mostly traumatic or caused by release of burn scars. The mean size of the flaps
      in the lower leg was 52 cm(2) (range 126-15 cm(2)). In the upper extremity it was
      24 cm(2) (range 12-35 cm(2)). All patients were followed until the wound had
      healed. In the upper extremity there was only one partial necrosis of the flap,
      and one patient had an infected wound. One haematoma was evacuated
      postoperatively, and all the rest healed uneventfully. In the lower leg we had
      one total necrosis and one partial necrosis of the flap and one infected wound. A
      free scapular flap was used for salvage in one case, and revision and skin
      grafting in two. The pedicled perforator flap is reliable, particularly in the
      upper extremity. The operation is quick and can be done under regional
      anaesthesia. The flap is thin and has a local texture that gives a good
      functional and aesthetic result. The pedicled perforator flap is a little
      unpredictable in the lower leg, probably because the directions of the vessels
      that arise from the perforator are not consistent.

PMID- 22455575
TI  - Treatment of venous ulcers with bone marrow-impregnated collagen matrix.
AB  - Bone marrow attracted our attention as a potentially beneficial material for the
      treatment of wounds, because it contains multipotential progenitor cells and
      produces growth factors. We impregnated autologous bone marrow cells on to a
      collagen matrix that had been used for the treatment of chronic wounds. The bone
      marrow-impregnated collagen matrix was then as a biomaterial scaffold for the
      treatment of wounds. This study was designed with the aim of clinically
      evaluating the effects of bone marrow-impregnated collagen matrix on wound
      healing of venous ulcers. We applied the matrix in 15 patients with chronic
      venous ulcers, and evaluated the transcutaneous oxygen tension (TcPO(2)) and
      vascular density. The application of the matrix induced healthy granulation
      tissue. All patients were given a split-thickness skin graft on to the induced
      granulation tissue, and have remained free from complications for more than eight
      months since the treatment. The mean (SD) vascular density at the ulcer base
      increased after the treatment (before 0.011 (0.006) mm(2)/mm(2), after 0.064
      (0.036) mm(2)/mm(2), p < 0.001). The periwound TcPO(2) values tended to increase
      (before 17.1 (12.7) mmHg, after 30.6 (13.4) mmHg, p < 0.001). Our results have
      shown the efficacy of bone marrow-impregnated collagen matrix for the treatment
      of intractable venous ulcers.

PMID- 22455577
TI  - Burden of illness in idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis is a life-threatening condition, and
      few data concerning the impact on healthcare utilization and associated costs are
      available. The objective of this study was to describe the burden of illness
      (comorbidity, healthcare resource utilization, and associated costs) in patients
      with idiopathic pulmonary fibrosis. METHODS: Two cohorts (patients with
      idiopathic pulmonary fibrosis and matched controls) were retrospectively
      identified from US claims databases between January 1, 2001 and September 30,
      2008. Cases with idiopathic pulmonary fibrosis were defined by age of 55 years or
      older and either two or more claims with a code for idiopathic fibrosing
      alveolitis (ICD-9 516.3), or one claim with ICD 516.3 and a subsequent claim with
      a code for post-inflammatory pulmonary fibrosis (ICD-9 515). The prevalence and
      incidence of pre-selected comorbidities, healthcare resource utilization
      (hospital, outpatient, drugs), and direct medical costs were assessed in each
      cohort. RESULTS: A total of 9286 patients with idiopathic pulmonary fibrosis were
      identified. When compared with age- and gender-matched controls, these patients
      were at significantly increased risk for comorbidities including pulmonary
      hypertension and emphysema. The all-cause hospital admission rate (0.5 per person
      year) and the all-cause outpatient visit rate (28.0 per person-year) were both ~2
      fold higher than in controls. Total direct costs for patients with idiopathic
      pulmonary fibrosis were $26,378 per person-year; the incremental costs over
      controls were $12,124 (2008 value). CONCLUSIONS: Patients with idiopathic
      pulmonary fibrosis experience increased comorbidity, healthcare resource
      utilization, and direct medical costs compared to controls.

PMID- 22455576
TI  - Multiple brown tumours of the upper extremity in a patient with secondary
      hyperparathyroidism as a result of chronic renal failure.
AB  - A man with chronic renal failure was referred to the hand clinic because of
      massive osteolytic tumours in his right arm. Secondary hyperparathyroidism and
      brown tumours were suggested, and he was treated by subtotal parathyroidectomy.
      Rapid reduction of the vast tumours was noted postoperatively.

PMID- 22455578
TI  - Synthesis of functionalized fluorescent indenes from electron-rich alpha-aryl
      ketonitriles.
AB  - A series of functionalized indenes bearing 1,3-dicyano groups were synthesized
      from electron-rich alpha-aryl ketonitriles in the presence of K(3)Fe(CN)(6) and
      NaOAc, possibly through tandem process involving dimerization, heterolytic
      cleavage of carbon-carbon bond, intermolecular coupling, and the subsequent
      intramolecular cyclization. The 2-arylindene compounds obtained possess good
      fluorescent properties.

PMID- 22455579
TI  - Bifunctional chelators in the design and application of radiopharmaceuticals for
      oncological diseases.
AB  - Radiopharmaceuticals constitute diagnostic and therapeutic tools for both
      clinical and preclinical applications. They are a blend of a tracer moiety that
      mediates a site specific accumulation and an effector: a radioisotope whose decay
      enables either molecular imaging or exhibits cytotoxic effects. Radioactive
      halogens and lanthanides are the most commonly used isotopes for
      radiopharmaceuticals. Due to their ready availability and the facile labeling
      metallic radionuclides offer ideal characteristics for applications in nuclear
      medicine. A stable link between the radionuclide and the carrier molecule is the
      primary prerequisite for in vivo applications. The radionuclide is selected
      according to its physical and chemical properties i.e. half-life, the type of
      decay, the energy emitted and its availability. Bifunctional chelating agents are
      used to stably link the radiometal to the carrier moiety of the
      radiopharmaceutical. The design of the bifunctional chelator has to consider the
      impact of the radiometal chelate on the biological properties of the target
      specific pharmaceutical. Here, with an emphasis on oncology, we review
      applications of radiopharmaceuticals that contain bifunctional chelators, while
      highlighting successes and identifying the key challenges that need to be
      addressed for the successful translation of target binding molecules into tracers
      for molecular imaging and endoradiotherapy.

PMID- 22455580
TI  - Iron chelators for the treatment of cancer.
AB  - The study of iron chelators as anti-tumor agents is still in its infancy. Iron is
      important for cellular proliferation and this is demonstrated by observations
      that iron-depletion results in cell cycle arrest and also apoptosis. In addition,
      many iron chelators are known to inhibit ribonucleotide reductase, the iron
      containing enzyme that is the rate-limiting step for DNA synthesis.
      Desferrioxamine is a well known chelator used for the treatment of iron-overload
      disease, but it has also been shown to possess anti-cancer activity. Another
      class of chelators, namely the thiosemicarbazones, have been shown to possess
      anti-cancer activity since the 1950's, although their mechanism(s) of action have
      only recently been more comprehensively elucidated. In fact, the redox activity
      of thiosemicarbazone iron complexes is thought to be important in mediating their
      potent cytotoxicity. Moreover, unlike typical iron chelators which simply act to
      deplete tumors of iron, several thiosemicarbazones (i.e., Bp44mT and Dp44mT) do
      not induce this effect, their anti-cancer efficacy being due to other mechanisms
      e.g., redox activity. Other reports have also shown that some thiosemicarbazones
      inhibit topoisomerase IIalpha, demonstrating that this class of agents have
      multiple molecular targets and act by various mechanisms. The most well
      characterized thiosemicarbazone iron chelator in terms of its assessment in
      humans is 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP). Observations
      from these clinical trials highlight the less than optimal activity of this
      ligand and several side effects related to its use, including myelo-suppression,
      hypoxia and methemoglobinemia. The mechanisms responsible for these latter
      effects must be elucidated and the design of the ligand altered to minimize these
      problems and increase efficacy. This review discusses the development of
      chelators as unique agents for cancer treatment.

PMID- 22455581
TI  - Deciphering the antimicrobial activity of phenanthroline chelators.
AB  - The opportunistic fungal pathogen, Candida albicans, causes a range of diseases
      in susceptible individuals. The adverse side effects of many of the current anti
      fungal prescription drugs and the emergence of C. albicans isolates and other
      Candida species which are resistant to these compounds have accelerated the
      search for new drug candidates which have different modes of action. A family of
      metal chelators, which are based on the 1,10-phenanthroline core, exhibit
      excellent growth inhibitory effects in vitro against a number of Candida species,
      including clinical isolates. The compounds sequester transition metal ions,
      damage mitochondrial function and uncouple cell respiration. Additionally, fungal
      cell morphology undergoes dramatic changes and there is evidence of apoptotic
      cell death. Importantly, in vivo studies have confirmed that the compounds have
      an acceptably low toxicity profile.

PMID- 22455583
TI  - Metal transport and homeostasis within the human body: toxicity associated with
      transport abnormalities.
AB  - In this work, latest reports about metal toxicity, transport and homeostasis have
      been thoroughly described and discussed. Although diseases associated with
      transport and homeostasis abnormalities are those of great interest, still a
      variety of the phenomena associated with these processes are under debate. In
      this paper, we try to summarize the newest theses on this topic, presenting
      contradictory points of view. We focus on toxic and essential metal pathways
      crossing and try to follow the exact metal binding molecules within the body and
      provide insight into the transport mechanism. Special attention is given to the
      mechanism of action of lately investigated metal transporters.

PMID- 22455582
TI  - Antimicrobial action of chelating agents: repercussions on the microorganism
      development, virulence and pathogenesis.
AB  - Infections caused by resistant microorganisms often fail to respond to
      conventional therapy, resulting in prolonged illness, increased treatment costs
      and greater risk of death. Consequently, the development of novel antimicrobial
      drugs is becoming more demanding every day since the existing drugs either have
      too many side-effects or they tend to lose effectiveness due to the selection of
      resistant strains. In view of these facts, a number of new strategies to obstruct
      vital biological processes of a microbial cell have emerged; one of these is
      focused on the use of metal-chelating agents, which are able to selectively
      disturb the essential metal metabolism of the microorganism by interfering with
      metal acquisition and bioavailability for crucial reactions. The chelation
      activity is able to inhibit the biological role of metal-dependent proteins
      (e.g., metalloproteases and transcription factors), disturbing the microbial cell
      homeostasis and culminating in the blockage of microbial nutrition, growth and
      development, cellular differentiation, adhesion to biotic (e.g., extracellular
      matrix components, cell and/or tissue) and abiotic (e.g., plastic, silicone and
      acrylic) structures as well as controlling the in vivo infection progression.
      Interestingly, chelating agents also potentiate the activity of classical
      antimicrobial compounds. The differences between the microorganism and host in
      terms of the behavior displayed in the presence of chelating agents could provide
      exploitable targets for the development of an effective chemotherapy for these
      diseases. Consequently, metal chelators represent a novel group of antimicrobial
      agents with potential therapeutic applications. This review will focus on the
      anti-fungal and anti-protozoan action of the most common chelating agents,
      deciphering and discussing their mode of action.

PMID- 22455584
TI  - Hydroxypyri(mi)dine-based chelators as antidotes of toxicity due to aluminum and
      actinides.
AB  - This review is focused on recent developments on hydroxypyri(mi)dines, as
      aluminum and actinide chelating agents to combat the toxicity due to
      accumulations of these metal ions in human body resulting from excessive metal
      exposure. After a brief update revision of the most common processes of aluminum
      (Al) exposure, as well as the associated toxicities and pathologies, we will
      focus on the current available Al chelators and future perspective as potential
      antidotes of Al toxicity. Due to the similarity between Al and Fe, a major
      emphasis is given to the hydroxypyridinone and hydroxypyrimidinone chelators,
      since they are analogues of the current iron chelators in clinical use (DFP and
      DFO). This review includes issues such as molecular design strategies and
      corresponding effects on the associated physico-chemical properties, lipo
      hydrophilic balance, toxicity, in vivo bioassays and current clinical
      applications. The hydroxypyri(mi)dine chelators are also suitable for other hard
      metal ions, such as the radiotoxic actinides, and so a brief review is included
      on the applications of these chelators in actinides scavenging.

PMID- 22455585
TI  - Chelating agents for metal intoxication.
AB  - In this paper we took into examination the use of chelation therapy for treating
      metal intoxication in humans. We divided this paper in four main parts: before
      all the principal causes of toxicity are exposed; second the chemical
      requirements (thermodynamic and kinetic), the interactions with the endogenous
      molecules and the target organs, as well as the biomedical restraints; as a third
      step the classes of chelators in use along with the specific treatments allowed
      are treated and as a final step the principal toxic metal ions are presented.
      Based on the presented material some conclusion are drawn on the state of art of
      metal chelation, and the basis are given for a rationale development of metal
      chelation, founded on chemical, biological and medical considerations.

PMID- 22455586
TI  - Chelating agents for the treatment of systemic iron overload.
AB  - The first successful therapeutic iron chelator was desferrioxamine which was
      introduced in the late 1960's by Ciba (now Novartis). Desferrioxamine has been an
      extremely successful compound having received the MMW "Pharmaceutical of the
      year" award for 1991. It is a life saving and a life - prolonging drug which
      improves the quality of life. However it is not orally active and its
      administration is both uncomfortable and expensive. Over the past twenty years
      there has been a growing interest in the orally active iron chelators,
      deferiprone and exjade, both having been extensively studied. The ability of
      these compounds to mobilize iron from the heart and endocrine tissue has
      presented the clinician with some advantages over desferrioxamine. Other orally
      active iron chelators are currently under development and one, FBS0701 is in
      clinical trial. The critical features necessary for the design of therapeutically
      useful iron chelators is presented in this review, together with recent studies
      devoted to the design of such chelators. This newly emerging range of iron
      chelators will enable clinicians to apply iron chelation methodology to other
      disease states and to begin to design personalised chelation regimes.

PMID- 22455587
TI  - Selective divalent copper chelation for the treatment of diabetes mellitus.
AB  - Oxidative stress and mitochondrial dysfunction have been identified by many
      workers as key pathogenic mechanisms in ageing-related metabolic, cardiovascular
      and neurodegenerative diseases (for example diabetes mellitus, heart failure and
      Alzheimer's disease). However, although numerous molecular mechanisms have been
      advanced to account for these processes, their precise nature remains obscure.
      This author has previously suggested that, in such diseases, these two mechanisms
      are likely to occur as manifestations of a single underlying disturbance of
      copper regulation. Copper is an essential but highly-toxic trace metal that is
      closely regulated in biological systems. Several rare genetic disorders of copper
      homeostasis are known in humans: these primarily affect various proteins that
      mediate intracellular copper transport processes, and can lead either to tissue
      copper deficiency or overload states. These examples illustrate how impaired
      regulation of copper transport pathways can cause organ damage and provide
      important insights into the impact of defects in specific molecular processes,
      including those catalyzed by the copper-transporting ATPases, ATP7A (mutated in
      Menkes disease), ATP7B (Wilson's disease), and the copper chaperones such as
      those for cytochrome c oxidase, SCO1 and SCO2. In diabetes, impaired copper
      regulation manifests as elevations in urinary CuII excretion, systemic chelatable
      CuII and full copper balance, in increased pro-oxidant stress and defective
      antioxidant defenses, and in progressive damage to the blood vessels, heart,
      kidneys, retina and nerves. Linkages between dysregulated copper and organ damage
      can be demonstrated by CuII-selective chelation, which simultaneously
      prevents/reverses both copper dysregulation and organ damage. Pathogenic
      structures in blood vessels that contribute to binding and localization of
      catalytically-active CuII probably include advanced glycation end products
      (AGEs), as well as atherosclerotic plaque: the latter probably undergoes AGE
      modification itself. Defective copper regulation mediates organ damage through
      two general processes that occur simultaneously in the same individual: elevation
      of CuII-mediated pro-oxidant stress and impairment of copper-catalyzed
      antioxidant defence mechanisms. This author has proposed that diabetes-evoked
      copper dysregulation is an important new target for therapeutic intervention to
      prevent/reverse organ damage in diabetes, heart failure, and neurodegenerative
      diseases, and that triethylenetetramine (TETA) is the first in a new class of
      anti-diabetic molecules, which function by targetting these copper-mediated
      pathogenic mechanisms. TETA prevents tissue damage and causes organ regeneration
      by acting as a highly-selective CuII chelator which suppresses copper-mediated
      oxidative stress and restores anti-oxidant defenses. My group has employed TETA
      in a comprehensive programme of nonclinical studies and proof-of-principle
      clinical trials, thereby characterizing copper dysregulation in diabetes and
      identifying numerous linked cellular and molecular mechanisms though which TETA
      exerts its therapeutic actions. Many of the results obtained in nonclinical
      models with respect to the molecular mechanisms of diabetic organ damage have not
      yet been replicated in patients' tissues so their applicability to the human
      disease must be considered as inferential until the results of informative
      clinical studies become available. Based on evidence from the studies reviewed
      herein, trientine is now proceeding into the later stages of pharmaceutical
      development for the treatment of heart failure and other diabetic complications.

PMID- 22455588
TI  - Chelating agents in different human diseases.

PMID- 22455589
TI  - Sirtuin modulators: mechanisms and potential clinical implications.
AB  - In the last years, studies about longevity have highlighted that caloric
      restriction can be linked with a less normal agingassociated damage, and in the
      same way, with the activity of the Silent Information Regulator 2 (SIR2) gene.
      Sir2-like genes, known as sirtuins (SIRTs), have been found in organisms ranging
      from bacteria to mammals promoting health and survival. At the moment, it has
      been identified seven classes of SIRTs in mammalian and the understanding of many
      of them remains still rudimentary. However, they are in the spotlight by their
      potential protection against aging-associated diseases and have emerged as key
      mediators of longevity in evolutionarily distant organisms models. SIRTs are
      proteins found in numerous compartments within the cell, which are NAD(+)
      dependent protein deacetylases and adenosine diphosphate (ADP)
      ribosyltransferases. They catalyse a reaction in which NAD(+) and an acetylated
      substrate are converted into a deacetylated substrate, nicotinamide and a novel
      metabolite O-acetyl ADP ribose. Therefore, its enzymatic activity requires
      NAD(+), which is a crucial molecule intermediary of many metabolic reactions in
      cells. Basically, SIRTs are mediators of aging process, they have the potential
      of ameliorating and taking part in important cellular processes associated, such
      as metabolic homeostasis, tumorigenesis and cancer cell proliferation,
      inflammatory disorders, cardiovascular diseases and neurodegeneration. This
      background opens up new lines of investigation into the modulation of SIRTs
      activity in order to develop novel therapeutic targets to these age-related
      diseases. Current experiments using molecule activators or inhibitors and
      genetically engineered animals have facilitated new insights into the role of
      these enzymes and contributed to highlight some of the potentially relevant
      targets. This review is intended to provide an appreciation of the possible
      protection against aging-associated diseases by these enzymes, summarize novel
      underlying mechanisms and evaluate potential clinical applications.

PMID- 22455591
TI  - Supramolecular approaches for drug development.
AB  - Various supramolecular systems can be used as drug carriers to alter
      physicochemical and pharmacokinetic characteristics of drugs. Representative
      supramolecular systems that can be used for this purpose include
      surfactant/polymer micelles, (micro)emulsions, liposomes, layer-by-layer
      assemblies, and various molecular conjugates. Notably, liposomes are established
      supramolecular drug carriers, which have already been marketed in formulations
      including AmBisome((r)) (for treatment of fungal infection), Doxil((r)) (for
      Kaposi's sarcoma), and Visudyne((r)) (for age-related macular degeneration and
      choroidal neovascularization). Microemulsions have been used oral drug delivery
      of poorly soluble drugs due to improvements in bioavailability and predictable of
      absorption behavior. Neoral((r)), an immunosuppressant used after transplant
      operations, is one of the most famous microemulsion-based drugs. Polymer micelles
      are being increasingly investigated as novel drug carriers and some formulations
      have already been tested in clinical trials. Supramolecular systems can be
      functionalized by designing the constituent molecules to achieve efficient
      delivery of drugs to desired sites in the body. In this review, representative
      supramolecular drug delivery systems, that may improve usability of candidate
      drugs or add value to existing drugs, are introduced.

PMID- 22455590
TI  - CuAAC click chemistry accelerates the discovery of novel chemical scaffolds as
      promising protein tyrosine phosphatases inhibitors.
AB  - Protein tyrosine phosphatases (PTPs) are crucial regulators for numerous
      biological processes in nature. The dysfunction and overexpression of many PTP
      members have been demonstrated to cause fatal human diseases such as cancers,
      diabetes, obesity, neurodegenerative diseases and autoimmune disorders. In the
      past decade, considerable efforts have been devoted to the production of PTPs
      inhibitors by both academia and the pharmaceutical industry. However, there are
      only limited drug candidates in clinical trials and no commercial drugs have been
      approved, implying that further efficient discovery of novel chemical entities
      competent for inhibition of the specific PTP target in vivo remains yet a
      challenge. In light of the click-chemistry paradigm which advocates the
      utilization of concise and selective carbon-heteroatom ligation reactions for the
      modular construction of useful compound libraries, the Cu(I)-catalyzed
      azidealkyne 1,3-dipolar cycloaddition reaction (CuAAC) has fueled enormous energy
      into the modern drug discovery. Recently, this ingenious chemical ligation tool
      has also revealed efficacious and expeditious in establishing large combinatorial
      libraries for the acquisition of novel PTPs inhibitors with promising
      pharmacological profiles. We thus offer here a comprehensive review highlighting
      the development of PTPs inhibitors accelerated by the CuAAC click chemistry.

PMID- 22455592
TI  - Recent advances in the development of 14-alkoxy substituted morphinans as potent
      and safer opioid analgesics.
AB  - Morphine and other opioid morphinans produce analgesia primarily through MU
      opioid receptors (MORs), which mediate beneficial but also non-beneficial
      actions. There is a continued search for efficacious opioid analgesics with
      reduced complications. The cornerstone in the development of 14-alkoxymorphinans
      as novel analgesic drugs was the synthesis of the highly potent MOR agonist 14-O
      methyloxymorphone. This opioid showed high antinociceptive potency but also the
      adverse effects associated with morphine type compounds. Further developments
      represent the introduction of a methyl and benzyl group at position 5 of 14-O
      methyloxymorphone leading to the strong opioid analgesics 14-methoxymetopon and
      its 5-benzyl analogue, which exhibited less pronounced side effects than morphine
      although interacting selectively with MORs. Introduction of arylalkyl
      substituents such as phenylpropoxy in position 14 led to a series of extremely
      potent antinociceptive agents with enhanced affinities at all three opioid
      receptor types. During the past years, medicinal chemistry and opioid research
      focused increasingly on exploring the therapeutic potential of peripheral opioid
      receptors by peripheralization of opioids in order to minimize the occurrence of
      centrally-mediated side effects. Strategies to reduce penetration to the central
      nervous system (CNS) include chemical modifications that increase hydrophilicity.
      Zwitterionic 6-amino acid conjugates of 14-Oalkyloxymorphones were developed in
      an effort to obtain opioid agonists that have limited access to the CNS. These
      compounds show high antinociceptive potency by interacting with peripheral MORs.
      Opioid drugs with peripheral site of action represent an important target for the
      treatment of severe and chronic pain without the adverse actions of centrally
      acting opioids.

PMID- 22455593
TI  - Role of microRNAs in gynecological pathology.
AB  - microRNAs (miRNAs) are 21-22 nucleotide non-coding RNAs that regulate gene
      expression and play fundamental roles in biological processes. These small
      molecules bind to target mRNAs, leading to translational repression and/or mRNA
      degradation. Aberrant miRNA expression is associated with several human diseases
      such as cancer, cardiovascular disorders, inflammatory diseases and gynecological
      pathology. The present article reviews the role of miRNAs in four gynecological
      disorders that affect the ovary or the uterus, one benign and frequent disease
      (endometriosis) that is classified as a tumor-like lesion and three malignant
      gynecological diseases (endometrial, cervical and ovarian cancers).
      Endometriosis, defined as the presence of endometrium outside the uterus, is one
      of the most frequent benign gynecological diseases. Similarly to tumor
      metastasis, endometriotic implants require neovascularization to proliferate,
      invade the extracellular matrix and establish an endometriotic lesion. Despite
      its high prevalence and incapacitating symptoms, the exact pathogenic mechanism
      of endometriosis remains unsolved. A relationship between endometriosis and
      gynecological cancer, especially ovarian cancer, has been reported. Endometriosis
      is a multifactorial and polygenic disease, and emerging data provide evidence
      that a dysregulation of miRNA expression may be involved. miRNAs appear to be
      potent regulators of gene expression in endometriosis, raising the prospect of
      using miRNAs as biomarkers and therapeutic tools in this disease. In cancer,
      miRNAs have an important role as regulatory molecules, acting as oncogenes
      (oncomiRs) or tumor suppressors. Endometrial cancer is one of the most frequent
      gynecological malignancies in the developed countries. Cervical cancer, also one
      of the most common cancers in women, is associated with high-risk human
      papillomaviruses although this infection alone may not be enough to induce the
      malignant transformation. Ovarian cancer is the fifth leading cause of all cancer
      related deaths among women. Over 80% of cases are diagnosed at an advanced stage,
      with a reduced five-year survival rate. Recent studies have shown that miRNAs are
      aberrantly expressed in different human cancer types, including endometrial,
      cervical and ovarian cancer, and that specific dysregulated miRNAs may act as
      biomarkers of patients' outcome. Recently, miRNAs have been detected in serum and
      plasma, and circulating miRNA expression profiles have now been associated with a
      range of different tumor types. Their accessibility in peripheral blood and
      stability given the fact that miRNAs circulate confined within exosomes, make
      researchers foster hope in their role as emerging biomarkers of cancer and other
      disorders. The development of therapies that might block the expression or mimic
      the functions of miRNAs could represent new therapeutic strategies for any of the
      aforementioned gynecological disorders.

PMID- 22455594
TI  - The quinoline imidoselenocarbamate EI201 blocks the AKT/mTOR pathway and targets
      cancer stem cells leading to a strong antitumor activity.
AB  - Methylimidoselenocarbamates have previously proven to display potent antitumor
      activities. In the present study we show that these compounds act as multikinase
      inhibitors. We found that the most effective compound, quinoline
      imidoselenocarbamate EI201, inhibits the PI3K/AKT/mTOR pathway, which is
      persistently activated and contributes to malignant progression in various
      cancers. EI201 blocked the phosphorylation of AKT, mTOR and several of its
      downstream regulators (p70S6K and 4E-BP1) and ERK1/2 in PC-3, HT-29 and MCF-7
      cells in vitro, inducing both autophagy and apoptosis. EI201 also contributes to
      the loss of maintenance of the selfrenewal and tumorigenic capacity of cancer
      stem cells (CSCs). 0.1 MUmol/L EI201 triggered a reduction in size and number of
      tumorspheres in PC-3, HT-29 and MCF-7 cells and 4 MUmol/L induced the elimination
      of almost all the tumorspheres in the three studied cell lines. In addition,
      EI201 suppressed almost 80% prostate tumor growth in vivo (p < 0.01) compared to
      controls at a relatively low dose (10 mg/kg) in a mouse xenograft model. There
      was a significant decrease in the subcutaneous primary tumor [18F]-FDG uptake
      (76.5% reduction, p < 0.05) and in the total tumor burden (76.8% reduction, p <
      0.05) after EI201 treatment compared to vehicle control, without causing toxicity
      in mice. Taken together, our results support further development of EI201 as a
      novel multi-kinase inhibitor that may be useful against cancers with aberrant
      upregulation of PI3K/AKT and MAPK signaling pathways.

PMID- 22455595
TI  - Barriers to and mediators of brain-computer interface user acceptance: focus
      group findings.
AB  - Brain-computer interfaces (BCI) are designed to enable individuals with severe
      motor impairments such as amyotrophic lateral sclerosis (ALS) to communicate and
      control their environment. A focus group was conducted with individuals with ALS
      (n=8) and their caregivers (n=9) to determine the barriers to and mediators of
      BCI acceptance in this population. Two key categories emerged: personal factors
      and relational factors. Personal factors, which included physical, physiological
      and psychological concerns, were less important to participants than relational
      factors, which included corporeal, technological and social relations with the
      BCI. The importance of these relational factors was analysed with respect to
      published literature on actor-network theory (ANT) and disability, and concepts
      of voicelessness and personhood. Future directions for BCI research are
      recommended based on the emergent focus group themes. PRACTITIONER SUMMARY: This
      manuscript explores human factor issues involved in designing and evaluating
      brain-computer interface (BCI) systems for users with severe motor disabilities.
      Using participatory research paradigms and qualitative methods, this work draws
      attention to personal and relational factors that act as barriers to, or
      mediators of, user acceptance of this technology.

PMID- 22455598
TI  - Effector and regulatory roles for B cells in HIV infection?
AB  - Toll-like receptor (TLR) signaling has been implicated in the genesis of HIV
      driven chronic immune activation and inflammation. In other inflammatory
      diseases, TLR driven B cell regulatory functions have been described, yet in HIV
      pathogenesis the focus has been on an antibody-dependent role for B cells. In
      this review, we discuss possible effector and regulatory functions exerted by
      (TLR) activated B cells during HIV infection.

PMID- 22455597
TI  - One-step multiplex real time RT-PCR for the detection of bovine respiratory
      syncytial virus, bovine herpesvirus 1 and bovine parainfluenza virus 3.
AB  - BACKGROUND: Detection of respiratory viruses in veterinary species has
      traditionally relied on virus detection by isolation or immunofluorescence and/or
      detection of circulating antibody using ELISA or serum neutralising antibody
      tests. Multiplex real time PCR is increasingly used to diagnose respiratory
      viruses in humans and has proved to be superior to traditional methods. Bovine
      respiratory disease (BRD) is one of the most common causes of morbidity and
      mortality in housed cattle and virus infections can play a major role. We
      describe here a one step multiplex reverse transcriptase quantitative polymerase
      chain reaction (mRT-qPCR) to detect the viruses commonly implicated in BRD.
      RESULTS: A mRT-qPCR assay was developed and optimised for the simultaneous
      detection of bovine respiratory syncytial virus (BRSV), bovine herpes virus type
      1 (BoHV-1) and bovine parainfluenza virus type 3 (BPI3 i & ii) nucleic acids in
      clinical samples from cattle. The assay targets the highly conserved glycoprotein
      B gene of BoHV-1, nucleocapsid gene of BRSV and nucleoprotein gene of BPI3. This
      mRT-qPCR assay was assessed for sensitivity, specificity and repeatability using
      in vitro transcribed RNA and recent field isolates. For clinical validation, 541
      samples from clinically affected animals were tested and mRT-qPCR result compared
      to those obtained by conventional testing using virus isolation (VI) and/or
      indirect fluorescent antibody test (IFAT). CONCLUSIONS: The mRT-qPCR assay was
      rapid, highly repeatable, specific and had a sensitivity of 97% in detecting 102
      copies of BRSV, BoHV-1 and BPI3 i & ii. This is the first mRT-qPCR developed to
      detect the three primary viral agents of BRD and the first multiplex designed
      using locked nucleic acid (LNA), minor groove binding (MGB) and TaqMan probes in
      one reaction mix. This test was more sensitive than both VI and IFAT and can
      replace the aforesaid methods for virus detection during outbreaks of BRD.

PMID- 22455599
TI  - Evaluation of the novel bipolar vessel sealing and cutting device BiCision(r) in
      a porcine model.
AB  - BACKGROUND: Energy-based technologies for tissue sealing and cutting are
      increasingly supplementing current standards used for haemostasis and dissection
      during laparoscopic surgery. For their safe and efficacious use in clinical
      practice, these instruments have to guarantee sufficient burst resistance and low
      thermal damage to adjacent tissue in combination with good cutting
      characteristics. MATERIAL AND METHODS: The novel laparoscopic, bipolar
      electrosurgical sealing and cutting instrument BiCision(r) was compared to a
      commercially available laparoscopic device (EnSeal(TM)) on visceral and
      peripheral arteries and veins in an animal model. RESULTS: For all parameters
      investigated (burst pressure, cut quality, tissue adhering to the instrument,
      time needed to seal and cut the vessel and thermal damage), BiCision(r) was at
      least as good as EnSeal(TM). Regarding the burst pressure, BiCision(r) was
      superior over EnSeal(TM) in arteries: 600 mmHg (+/-478) versus 241 (+/-269) mmHg,
      respectively (p < 0.0001*). In veins, almost equivalent burst pressures of 155 +/
      134 mmHg (BiCision(r)) and 173 +/- 139 mmHg (EnSeal(TM)) were obtained.
      CONCLUSION: BiCision(r) appeared to be as good as or even superior to EnSeal(TM).
      Since EnSeal(TM) has already been shown to be safe and has been successfully used
      in clinical practice, BiCision(r) is assumed to be as efficient and reliable as
      EnSeal(TM) under pre-clinical conditions.

PMID- 22455601
TI  - A new approach to highly substituted cyclopentanoids from a concise formal
      synthesis of (+)-roseophilin.
AB  - A convergent reaction sequence involving a reductive coupling and a chiral
      Bronsted acid catalyzed Nazarov reaction is utilized in a concise formal
      synthesis of (+)-roseophilin (11 steps via longest linear sequence, 10.2% yield,
      95% ee).

PMID- 22455600
TI  - The absence of dystrophin brain isoform expression in healthy human heart
      ventricles explains the pathogenesis of 5' X-linked dilated cardiomyopathy.
AB  - BACKGROUND: In X-linked dilated cardiomyopathy due to dystrophin mutations which
      abolish the expression of the M isoform (5'-XLDC), the skeletal muscle is spared
      through the up-regulation of the Brain (B) isoform, a compensatory mechanism that
      does not appear to occur in the heart of affected individuals. METHODS: We
      quantitatively studied the expression topography of both B and M isoforms in
      various human heart regions through in-situ RNA hybridization, Reverse
      Transcriptase and Real-Time PCR experiments. We also investigated the methylation
      profile of the B promoter region in the heart and quantified the B isoform up
      regulation in the skeletal muscle of two 5'-XLDC patients. RESULTS: Unlike the M
      isoform, consistently detectable in all the heart regions, the B isoform was
      selectively expressed in atrial cardiomyocytes, but absent in ventricles and in
      conduction system structures. Although the level of B isoform messenger in the
      skeletal muscle of 5'-XLDC patients was lower that of the M messenger present in
      control muscle, it seems sufficient to avoid an overt muscle pathology. This
      result is consistent with the protein level in XLDC patients muscles we
      previously quantified. Methylation studies revealed that the B promoter shows an
      overall low level of methylation at the CG dinucleotides in both atria and
      ventricles, suggesting a methylation-independent regulation of the B promoter
      activity. CONCLUSIONS: The ventricular dilatation seen in 5'-XLDC patients
      appears to be functionally related to loss of the M isoform, the only isoform
      transcribed in human ventricles; in contrast, the B isoform is well expressed in
      heart but confined to the atria. Since the B isoform can functionally replace the
      M isoform in the skeletal muscle, its expression in the heart could potentially
      exert the same rescue function. Methylation status does not seem to play a role
      in the differential B promoter activity in atria and ventricles, which may be
      governed by other regulatory mechanisms. If these mechanisms could be deduced, de
      silencing of the B isoform may represent a therapeutic strategy in 5'-XLDC
      patients.

PMID- 22455602
TI  - Self-assembly of charged Bodipy dyes to form Cassettes that display intracomplex
      electronic energy transfer and accrete into liquid crystals.
AB  - Red- and blue-absorbing boron dipyrromethene dyes, bearing opposite electronic
      charges, associate in solution to form a 1:2 complex having a stability constant
      of ca. 10(17) M(-2). The complex can be dismantled by addition of a large excess
      of tetra-N-butylammonium cations. The same complex displays liquid crystalline
      properties on heating from rt to above 150  degrees C, as characterized by
      various experimental techniques. Highly efficient electronic energy transfer from
      the red to the blue dye occurs in both the initial complex and the subsequent
      mesomorphic state.

PMID- 22455603
TI  - Effect of activated carbon amendment on bacterial community structure and
      functions in a PAH impacted urban soil.
AB  - We collected urban soil samples impacted by polycyclic aromatic hydrocarbons
      (PAHs) from a sorbent-based remediation field trial to address concerns about
      unwanted side-effects of 2% powdered (PAC) or granular (GAC) activated carbon
      amendment on soil microbiology and pollutant biodegradation. After three years,
      total microbial cell counts and respiration rates were highest in the GAC amended
      soil. The predominant bacterial community structure derived from denaturing
      gradient gel electrophoresis (DGGE) shifted more strongly with time than in
      response to AC amendment. DGGE band sequencing revealed the presence of taxa with
      closest affiliations either to known PAH degraders, e.g. Rhodococcus jostii RHA
      1, or taxa known to harbor PAH degraders, e.g. Rhodococcus erythropolis, in all
      soils. Quantification by real-time polymerase chain reaction yielded similar
      dioxygenases gene copy numbers in unamended, PAC-, or GAC-amended soil. PAH
      availability assessments in batch tests showed the greatest difference of 75%
      with and without biocide addition for unamended soil, while the lowest PAH
      availability overall was measured in PAC-amended, live soil. We conclude that AC
      had no detrimental effects on soil microbiology, AC-amended soils retained the
      potential to biodegrade PAHs, but the removal of available pollutants by
      biodegradation was most notable in unamended soil.

PMID- 22455604
TI  - Concern over radiation exposure and psychological distress among rescue workers
      following the Great East Japan Earthquake.
AB  - BACKGROUND: On March 11, 2011, the Great East Japan Earthquake and tsunami that
      followed caused severe damage along Japans northeastern coastline and to the
      Fukushima Daiichi nuclear power plant. To date, there are few reports
      specifically examining psychological distress in rescue workers in Japan.
      Moreover, it is unclear to what extent concern over radiation exposure has caused
      psychological distress to such workers deployed in the disaster area. METHODS:
      One month after the disaster, 424 of 1816 (24%) disaster medical assistance team
      workers deployed to the disaster area were assessed. Concern over radiation
      exposure was evaluated by a single self-reported question. General psychological
      distress was assessed with the Kessler 6 scale (K6), depressive symptoms with the
      Center for Epidemiologic Studies Depression Scale (CES-D), fear and sense of
      helplessness with the Peritraumatic Distress Inventory (PDI), and posttraumatic
      stress symptoms with the Impact of Event Scale-Revised (IES-R). RESULTS:
      Radiation exposure was a concern for 39 (9.2%) respondents. Concern over
      radiation exposure was significantly associated with higher scores on the K6, CES
      D, PDI, and IES-R. After controlling for age, occupation, disaster operation
      experience, duration of time spent watching earthquake news, and past history of
      psychiatric illness, these associations remained significant in men, but did not
      remain significant in women for the CES-D and PDI scores. CONCLUSION: The
      findings suggest that concern over radiation exposure was strongly associated
      with psychological distress. Reliable, accurate information on radiation exposure
      might reduce deployment-related distress in disaster rescue workers.

PMID- 22455605
TI  - Replication study confirms the association between UBAC2 and Behcet's disease in
      two independent Chinese sets of patients and controls.
AB  - INTRODUCTION: The purpose of this study was to replicate genetic factors
      associated with the susceptibility to Behcet's disease (BD). We conducted a two
      stage candidate genes association and functional study, involving 477 BD patients
      and 1,334 normal controls of Chinese Han descent. METHODS: The genotyping of five
      candidate genes/loci, including LOC100129342, KIAA1529, CPVL, UBASH3B and UBAC2,
      were performed using TaqMan single nucleotide polymorphism (SNP) assays. Real
      time PCR and luciferase reporter assay were performed to test the function of the
      identified promoter polymorphism. The main outcome measures were genotype
      frequencies and expression levels in BD patients. RESULTS: The first-stage study
      results showed that UBAC2 (rs9513584, Pc = 0.018, OR = 1.4), but not
      LOC100129342, KIAA1529, CPVL, UBASH3B was associated with the susceptibility to
      BD in Chinese Han. The fine-mapping association study of UBAC2 identified six
      risk SNPs for BD in the Chinese cohort; three of them were verified in validation
      study (rs3825427, first-stage Pc = 2.2 * 10-3, second-stage Pc = 9.3 * 10-3,
      combined Pc = 6.9 * 10-6; rs9517668, first-stage Pc = 1.7 * 10-3, second-stage Pc
      = 0.03, combined Pc = 3.3 * 10-4; rs9517701, first-stage Pc = 5.1 * 10-3, second
      stage Pc = 9.0 * 10-3, combined Pc = 2.9 * 10-5; respectively). Functional
      analysis showed that the risk T allele of the promoter polymorphism rs3825427 had
      a significantly lower promoter activity than the non-risk G allele (P = 0.002)
      and a decreased expression of UBAC2 transcript variant 1 in peripheral blood
      mononuclear cells (PBMCs) and skin of normal controls carrying the risk T allele
      than that in individuals with the G allele (P = 0.045, P = 0.025; respectively).
      The mRNA expression of UBAC2 transcript variant 1 was significantly decreased in
      PBMCs and skin of BD patients as compared with controls (P = 0.025; P = 0.047,
      respectively). The mRNA expression of UBAC2 transcript variant 2 was
      significantly increased in skin of BD patients as compared with controls (P =
      0.004). CONCLUSIONS: This study replicates a predisposition gene to BD, UBAC2,
      and suggests that UBAC2 may be involved in the development of BD through its
      transcriptional modulation.

PMID- 22455606
TI  - Cluster secondary ion mass spectrometry and the temperature dependence of
      molecular depth profiles.
AB  - The quality of molecular depth profiles created by erosion of organic materials
      by cluster ion beams exhibits a strong dependence upon temperature. To elucidate
      the fundamental nature of this dependence, we employ the Irganox 3114/1010
      organic delta-layer reference material as a model system. This delta-layer system
      is interrogated using a 40 keV C(60)(+) primary ion beam. Parameters associated
      with the depth profile such as depth resolution, uniformity of sputtering yield,
      and topography are evaluated between 90 and 300 K using a unique wedge-crater
      beveling strategy that allows these parameters to be determined as a function of
      erosion depth from atomic force microscope (AFM) measurements. The results show
      that the erosion rate calibration performed using the known Delta-layer depth in
      connection with the fluence needed to reach the peak of the corresponding
      secondary ion mass spectrometry (SIMS) signal response is misleading. Moreover,
      we show that the degradation of depth resolution is linked to a decrease of the
      average erosion rate and the buildup of surface topography in a thermally
      activated manner. This underlying process starts to influence the depth profile
      above a threshold temperature between 210 and 250 K for the system studied here.
      Below that threshold, the process is inhibited and steady-state conditions are
      reached with constant erosion rate, depth resolution, and molecular secondary ion
      signals from both the matrix and the Delta-layers. In particular, the results
      indicate that further reduction of the temperature below 90 K does not lead to
      further improvement of the depth profile. Above the threshold, the process
      becomes stronger at higher temperature, leading to an immediate decrease of the
      molecular secondary ion signals. This signal decay is most pronounced for the
      highest m/z ions but is less for the smaller m/z ions, indicating a shift toward
      small fragments by accumulation of chemical damage. The erosion rate decay and
      surface roughness buildup, on the other hand, exhibit a rather sudden delayed
      onset after erosion of about 150 nm, indicating that a certain damage level must
      be reached in order to influence the erosion dynamics. Only after that onset does
      the depth resolution become compromised, indicating that the temperature
      reduction does not significantly influence parameters like ion-beam mixing or the
      altered-layer thickness. In general, the wedge-crater beveling protocol is shown
      to provide a powerful basis for increased understanding of the fundamental
      factors that affect the important parameters associated with molecular depth
      profiling.

PMID- 22455607
TI  - Clinical associations in patients with hand osteoarthritis.
AB  - OBJECTIVES: To investigate the clinical associations of hand osteoarthritis (HOA)
      and their relationships with radiographic features. METHODS: A total of 446
      patients with hand osteoarthritis (HOA; 233 with erosive HOA (EHOA) and 213 with
      non-EHOA) and 307 controls were evaluated. Demographic and clinical data from
      patients and controls were recorded based on medical records/clinical reports and
      an anamnesis of drug consumption. Posteroanterior radiographs of both hands were
      obtained from all HOA patients and were assessed using the Kellgren and Lawrence
      (K&L) and Kallman scoring systems. RESULTS: After adjustment for age, gender, and
      body mass index (BMI), HOA patients showed a significantly increased odds ratio
      (OR) for hypercholesterolaemia [OR 2.10, 95% confidence interval (CI) 1.39-3.16,
      p < 0.0005] and autoimmune thyroiditis (OR 4.85, 95% CI 1.77-13.29, p = 0.002),
      as well as for knee (OR 1.63, 95% CI 1.09-2.44, p = 0.018) and hip OA (OR 1.87,
      95% CI 1.07-3.27, p = 0.029). No significant increase for systemic hypertension,
      ischaemic heart disease, and diabetes mellitus was found. Patients with EHOA and
      non-EHOA showed similar risks for the above-mentioned co-morbidities. A similar
      occurrence of clinical associations was also observed in patients with HOA alone
      and in those with generalized OA. No association between radiographic scores and
      clinical associations was observed. CONCLUSIONS: Patients with HOA present a
      direct association with hypercholesterolaemia (and autoimmune thyroiditis) but do
      not show increased ischaemic cardiovascular manifestations compared to controls.
      No significant association between radiographic scores and co-morbidities was
      found.

PMID- 22455608
TI  - NIST gravimetrically prepared atmospheric level methane in dry air standards
      suite.
AB  - The Gas Metrology Group at the National Institute of Standards and Technology was
      tasked, by a congressional climate change act, to support the atmospheric
      measurement community through standards development of key greenhouse gases. This
      paper discusses the development of a methane (CH(4)) primary standard gas mixture
      (PSM) suite to support CH(4) measurement needs over a large amount-of-substance
      fraction range 0.3-20,000 MUmol mol(-1), but with emphasis at the atmospheric
      level 300-4000 nmol mol(-1). Thirty-six CH(4) in dry air PSMs were prepared in
      5.9 L high-pressure aluminum cylinders with use of a time-tested gravimetric
      technique. Ultimately 14 of these 36 PSMs define a CH(4) standard suite covering
      the nominal ambient atmospheric range of 300-4000 nmol mol(-1). Starting
      materials of pure CH(4) and cylinders of dry air were exhaustively analyzed to
      determine the purity and air composition. Gas chromatography with flame
      ionization detection (GC-FID) was used to determine a CH(4) response for each of
      the 14 PSMs where the reproducibility of average measurement ratios as a standard
      error was typically (0.04-0.26) %. An ISO 6134-compliant generalized least
      squares regression (GenLine) program was used to analyze the consistency of the
      CH(4) suite. All 14 PSMs passed the u-test with residuals between the gravimetric
      and the GenLine solution values being between -0.74 and 1.31 nmol mol(-1); (0.00
      0.16)% relative absolute. One of the 14 PSMs, FF4288 at 1836.16 +/- 0.75 nmol
      mol(-1) (k = 1) amount-of-substance fraction, was sent to the Korea Research
      Institute of Standards and Science (KRISS), the Republic of Korea's National
      Metrology Institute, for comparison. The same PSM was subsequently sent to the
      National Oceanic and Atmospheric Administration (NOAA) for analysis to their
      standards. Results show agreement between KRISS-NIST of +0.13% relative (+2.3
      nmol mol(-1)) and NOAA-NIST of -0.14% relative (-2.54 nmol mol(-1)).

PMID- 22455609
TI  - Pleiotropic-acting nutrients require integrative investigational approaches: the
      example of flavonoids.
AB  - Assessment of the health effects of dietary interventions in humans poses a
      particular challenge to nutritional and clinical scientists. In contrast to drugs
      possessing a well-defined molecular mechanism of action, food-derived components
      act in subtle and pleiotropic ways by nature. Moreover, dietary compounds are
      mainly not intended to cure a disease but to prevent or beneficially affect
      situations when the physiology gets slightly out of homeostasis. By the example
      of a recent clinical pilot study, this paper illustrates an endeavor to find new
      strategies for the detection of health effects of flavonoids in the human
      vasculature. Integration of a meticulously selected cluster of relevant
      biomarkers eventually enabled the beneficial vascular health effects of
      flavonoids to be revealed. A critical appraisal of this approach for the future
      is provided.

PMID- 22455610
TI  - Study on reconstruction of rectal sensation based on wavelet packet analysis and
      SVM strategy.
AB  - To control anal incontinence, we have developed an artificial anal sphincter
      system with sensor feedback. The artificial anal sphincter system is a novel
      hydraulic-electric muscle which mainly comprises an artificial anal sphincter, a
      wireless power supply subsystem, and a rectal sensation reconstruction subsystem.
      To investigate the features of the patients' rectal sensation, we have developed
      an in vitro experimental platform of artificial anal sphincter. In vitro
      experiments have been performed, and demonstrate that the traditional threshold
      method is not suitable for predicting the time for defecation. The traditional
      threshold method only uses single-dimensional pressure time series which may
      contain a few interdependent components simultaneously. A wavelet packet analysis
      algorithm is employed to extract the feature vector of the rectal pressure
      signal, then the rectal sensation prediction model is constructed based on a
      support vector machine for defecation pattern recognition. The results show that
      the proposed method is an effective approach for the reconstruction of patients'
      rectal sensation.

PMID- 22455612
TI  - Biomimetic dual sensing-actuators based on conducting polymers. Galvanostatic
      theoretical model for actuators sensing temperature.
AB  - A theoretical model is proposed for the quantitative description of the
      chronopotentiometric (E-t) responses, under galvanostatic control, of either
      conducting polymer films or dual sensing-actuating devices. Assuming that the
      reaction occurs by extraction, or injection, of n consecutive electrons from, or
      to, a polymer chain the material moves through n consecutive oxidation or
      reduction states. Stair functions are obtained describing either potential or
      consumed electrical energy evolutions as a function of both, driving (current)
      and environmental (temperature, electrolyte concentration...) variables. The
      current quantifies the actuation of any electrochemical device (charge/discharge
      of batteries, movement rate, and position of muscles): the stair functions are
      dual actuating-sensing functions. A good agreement exists between theoretical and
      experimental results from either polypyrrole films or artificial muscles at
      different temperatures. Only two connecting wires include, at any time, sensing
      (potential) and working (current) information of any dual device.

PMID- 22455611
TI  - Prevalence and molecular characterization of Clostridium difficile isolated from
      feedlot beef cattle upon arrival and mid-feeding period.
AB  - BACKGROUND: The presence of indistinguishable strains of Clostridium difficile in
      humans, food animals and food, as well as the apparent emergence of the food
      animal-associated ribotype 078/toxinotype V as a cause of community-associated C.
      difficile infection have created concerns about the potential for foodborne
      infection. While studies have reported C. difficile in calves, studies of cattle
      closer to the age of harvest are required. Four commercial feedlots in Alberta
      (Canada) were enrolled for this study. Fecal samples were collected at the time
      of arrival and after acclimation (< 62, 62-71 or > 71 days on feed). Selective
      culture for Clostridium difficile was performed, and isolates were characterized
      by ribotyping and pulsed-field gel electrophoresis. A logistic regression model
      was built to investigate the effect of exposure to antimicrobial drugs on the
      presence of C. difficile. RESULTS: Clostridium difficile was isolated from 18 of
      539 animals at the time of feedlot arrival (CI = 2.3-6.1) and from 18 of 335
      cattle at mid-feeding period (CI = 2.9-13.1). Overall, there was no significant
      difference in the prevalence of C. difficile shedding on arrival versus mid
      feeding period (P = 0.47). No association between shedding of the bacterium and
      antimicrobial administration was found (P = 0.33). All the isolates recovered
      were ribotype 078, a toxinotype V strain with genes encoding toxins A, B and CDT.
      In addition, all strains were classified as NAP7 by pulsed field gel
      electrophoresis (PFGE) and had the characteristic 39 base pairs deletion and
      upstream truncating mutation on the tcdC gene. CONCLUSIONS: It is apparent that
      C. difficile is carried in the intestinal tracts of a small percentage of feedlot
      cattle arriving and later in the feeding period and that ribotype 078/NAP7 is the
      dominant strain in these animals. Herd management practices associated with C.
      difficile shedding were not identified, however further studies of the potential
      role of antimicrobials on C. difficile acquisition and shedding are required.

PMID- 22455613
TI  - Cardioprotective effects of rosuvastatin and carvedilol on delayed cardiotoxicity
      of doxorubicin in rats.
AB  - CONTEXT: Doxorubicin is widely used anti-neoplastic drug but has serious
      cardiotoxicity. Long-term cardioprotective effects of statin and carvedilol
      against delayed cardiotoxicity of doxorubicin was not well elucidated. OBJECTIVE:
      To evaluate long-term cardioprotective effects of co-administered rosuvastatin
      and carvedilol against chronic doxorubicin-induced cardiomyopathy (DIC) in rats.
      METHODS: Sixty-one rats were assigned to six groups: group I, control; group II,
      doxorubicin only (1.25 mg/kg, bi-daily, I.P.); group III, doxorubicin +
      rosuvastatin (2 mg/kg/day, P.O.); group IV, doxorubicin + rosuvastatin(10
      mg/kg/day, P.O.); group V, doxorubicin + carvedilol (5 mg/kg/day, P.O.); group
      VI, doxorubicin + carvedilol (10 mg/kg/day, P.O.). Drugs were administered for 4
      weeks (by week 4) and rats were observed without drugs for 4 weeks (by week 8).
      RESULTS: After 4 weeks discontinuation of drugs (week 8), group III showed higher
      +dP/dt (p = 0.058), lower -dP/dt (p = 0.009), lower left ventricular (LV) tissue
      malondialdehyde (MDA; p = 0.022), and less LV fibrosis (p = 0.011) than group II.
      Group IV showed similar results to group III. However, in group V and VI,
      carvedilol failed to reduce LV dysfunction, elevation of troponin or myocardial
      fibrosis, although group V showed lower LV tissue MDA (p = 0.004) than group II.
      DISCUSSION AND CONCLUSIONS: Myocardial injury and LV systolic/diastolic
      dysfunction at week 8 was alleviated by co-administered rosuvastatin, but not by
      carvedilol. It is unclear whether the cardioprotective effect of rosuvastatin is
      attributed to a suppression of oxidative stress induced by doxorubicin, because
      carvedilol did not exhibit a cardioprotective effect despite its antioxidant
      effects.

PMID- 22455614
TI  - Community involvement in obstetric emergency management in rural areas: a case of
      Rukungiri district, Western Uganda.
AB  - BACKGROUND: Maternal mortality is a major public health problem worldwide
      especially in low income countries. Most causes of maternal deaths are due to
      direct obstetric complications. Maternal mortality ratio remains high in
      Rukungiri district, western Uganda estimated at 475 per 100,000 live births. The
      objectives were to identify types of community involvement and examine factors
      influencing the level of community involvement in the management of obstetric
      emergencies. METHODS: We conducted a descriptive study during 2nd to 28th
      February 2009 in rural Rukungiri district, western Uganda. A total of 448 heads
      of households, randomly selected from 6/11 (54.5%) of sub-counties, 21/42 (50.0%)
      parishes and 32/212 (15.1%) villages (clusters), were interviewed. Data were
      analysed using STATA version 10.0. RESULTS: Community pre-emergency support
      interventions available included community awareness creation (sensitization)
      while interventions undertaken when emergency had occurred included
      transportation and referring women to health facility. Community support
      programmes towards health care (obstetric emergencies) included establishment of
      community savings and credit schemes, and insurance schemes. The factors
      associated with community involvement in obstetric emergency management were
      community members being employed (AOR = 1.91, 95% CI: 1.02 - 3.54) and rating the
      quality of maternal health care as good (AOR = 2.22, 95% CI: 1.19 - 4.14).
      CONCLUSIONS: Types of community involvement in obstetric emergency management
      include practices and support programmes. Community involvement in obstetric
      emergency management is influenced by employment status and perceived quality of
      health care services. Policies to promote community networks and resource
      mobilization strategies for health care should be implemented. There is need for
      promotion of community support initiatives including health insurance schemes and
      self help associations; further community sensitization by empowered community
      based resource persons rather than health workers and improvement in quality of
      health care can contribute towards effective management of obstetric
      complications.

PMID- 22455615
TI  - Accuracy of needle position measurements using fiber Bragg gratings.
AB  - Accurate placement of the needle tip is essential in percutaneous therapies such
      as radiofrequency ablation (RFA) of liver tumors. Use of a robotic system for
      navigating the needle could improve the targeting accuracy. Real-time information
      on the needle tip position is needed, since a needle deflects during insertion in
      tissue. Needle shape can be reconstructed based on strain measurements within the
      needle. In the current experiment we determined the accuracy with which the
      needle tip position can be derived from strain measurements using Fiber Bragg
      Gratings (FBGs). Three glass fibers equipped with two FBGs each were incorporated
      in a needle. The needle was clamped at one end and deformed by applying static
      radial displacements at one or two locations. The FBG output was used for offline
      estimation of the needle shape and tip position. During deflections of the needle
      tip up to 12.5 mm, the tip position was estimated with a mean accuracy of 0.89 mm
      (std 0.42 mm). Adding a second deflection resulted in an error of 1.32 mm (std
      0.48 mm). This accuracy is appropriate for applications such as RFA of liver
      tumors. The results further show that the accuracy can be improved by optimizing
      the placement of FBGs.

PMID- 22455616
TI  - Navigated laparoscopy--liver shift and deformation due to pneumoperitoneum in an
      animal model.
AB  - BACKGROUND: Precise laparoscopic liver resection requires accurate planning and
      visualization of important anatomy such as vessels and tumors. Combining
      laparoscopic ultrasound with navigation technology could provide this.
      Preoperative images are valuable for planning and overview of the procedure,
      while intraoperative images provide an updated view of the surgical field.
      PURPOSE: To validate the accuracy of navigation technology based on preoperative
      images, we need to understand how much the liver shifts and deforms due to
      heartbeat, breathing, surgical manipulation and pneumoperitoneum. In this study,
      we evaluated liver tumor shift and deformation due to pneumoperitoneum in an
      animal model. METHODS: Tumor models were injected into the liver of the animal,
      and 3D CT images were acquired before and after insufflation. Tumor shifts and
      deformation were determined. RESULTS: The results showed significant tumor
      position shift due to pneumoperitoneum, with a maximum of 28 mm in cranio-caudal
      direction. No significant tumor deformation was detected. Small standard
      deviations suggest rigid body transformation of the liver as a whole, but this
      needs further investigation. CONCLUSION: The findings indicate a need for
      anatomic shift correction of preoperative images before they are used in
      combination with LUS guidance during a laparoscopic liver resection procedure.

PMID- 22455618
TI  - Feasibility and complications in bipolar resectoscopy: preliminary experience.
AB  - OBJECTIVE: To evaluate whether the new bipolar resectoscope (BR) 22 Fr (Karl
      Storz) represents a reliable improvement in operative hysteroscopy and to compare
      the new device to the 26 Fr BR (Karl Storz). MATERIAL AND METHODS: A prospective
      observational study. From June 2010 through May 2011, 158 consecutive patients
      treated with bipolar resectoscope 22 Fr and 26 Fr for endocavitary pathologies
      were registered. Data analysis included patients'characteristics, surgical
      indications, operative time and complications. 140 patients were eligible.
      RESULTS: 115/140 (82.1%) patients were treated by BR 22; 55 (39.2%)
      metroplastics, 34 (24.2%) polipectomies, 25 (17.8%) myomectomies and one (0.71%)
      sinechiolisis were performed. 25/140 (17.8%) patients were treated by BR 26; 6
      (4.2%) polipectomies and 19 (13.5%) myomectomies were performed. Mean time of
      cervical dilatation by Hegar series was 57 sec for BR 22 Fr and 102 sec for BR 26
      Fr (p = 0.034). 4/25 (16%) with 26BR and 1/115 (0.8%) with 22BR complications
      were observed (p = 0.002) : One uterine perforation, two post operative bleedings
      > 7 days, one intravasation syndrome and one cervical laceration. CONCLUSION:
      Bipolar resectoscopy is feasible and safe. The new device BR 22 Fr is preferable
      to 26 Fr because it requires lower cervical dilatation limiting operative time
      and complications.

PMID- 22455617
TI  - Laparoscopic incisional and ventral hernia repair (LIVHR) with PARIETEXTM
      Composite mesh.
AB  - OBJECTIVES: Laparoscopic incisional and ventral hernia repair (LIVHR) is widely
      used although its clinical indications are often debated. The aim of this study
      was to retrospectively describe the experience of our surgical centre in order to
      establish the safety, efficacy, and feasibility of LIVHR using PARIETEX(TM)
      Composite mesh (Covidien, Mansfield, MA, USA). MATERIAL AND METHODS: Between
      January 2007 and November 2010, 87 patients were admitted to the Division of
      General Surgery of Aosta, with the diagnosis of abdominal wall hernia and
      underwent laparoscopic repair using PARIETEX(TM) Composite mesh. The type and
      size of surgical defects, mean operative time, morbidity, mortality and rate of
      recurrence at one-year follow-up were retrospectively analysed. RESULTS: We
      performed 87 LIVHR: 51.7% for incisional hernia and 48.3% for epigastric or
      umbilical hernias. Mean operative time was 100 min., conversion rate was 3.4%.
      The mean size of abdominal defect was 6 cm (range: 2-15); in relation to
      umbilical hernias, mean size was 5.4 cm (range: 2-8). The mortality rate was 0%;
      overall morbidity was 16%. At one-year follow-up, we observed two cases of hernia
      recurrences. CONCLUSIONS: LIVHR using PARIETEX(TM) Composite mesh is an effective
      and safe procedure with very low morbidity and low rates of postoperative pain
      and recurrence, especially in hernias with diameter of between 5 and 15 cm and in
      obese patients without previous laparotomies.

PMID- 22455619
TI  - Folding mechanism of an extremely thermostable (betaalpha)(8)-barrel enzyme: a
      high kinetic barrier protects the protein from denaturation.
AB  - HisF, the cyclase subunit of imidazole glycerol phosphate synthase (ImGPS) from
      Thermotoga maritima, is an extremely thermostable (betaalpha)(8)-barrel protein.
      We elucidated the unfolding and refolding mechanism of HisF. Its unfolding
      transition is reversible and adequately described by the two-state model, but 6
      weeks is necessary to reach equilibrium (at 25  degrees C). During refolding,
      initially a burst-phase off-pathway intermediate is formed. The subsequent
      productive folding occurs in two kinetic phases with time constants of ~3 and ~20
      s. They reflect a sequential process via an on-pathway intermediate, as revealed
      by stopped-flow double-mixing experiments. The final step leads to native HisF,
      which associates with the glutaminase subunit HisH to form the functional ImGPS
      complex. The conversion of the on-pathway intermediate to the native protein
      results in a 10(6)-fold increase of the time constant for unfolding from 89 ms to
      35 h (at 4.0 M GdmCl) and thus establishes a high energy barrier to denaturation.
      We conclude that the extra stability of HisF is used for kinetic protection
      against unfolding. In its refolding mechanism, HisF resembles other
      (betaalpha)(8)-barrel proteins.

PMID- 22455620
TI  - Enhanced analyte detection using in-source fragmentation of field asymmetric
      waveform ion mobility spectrometry-selected ions in combination with time-of
      flight mass spectrometry.
AB  - Miniaturized ultra high field asymmetric waveform ion mobility spectrometry
      (FAIMS) is used for the selective transmission of differential mobility-selected
      ions prior to in-source collision-induced dissociation (CID) and time-of-flight
      mass spectrometry (TOFMS) analysis. The FAIMS-in-source collision induced
      dissociation-TOFMS (FISCID-MS) method requires only minor modification of the ion
      source region of the mass spectrometer and is shown to significantly enhance
      analyte detection in complex mixtures. Improved mass measurement accuracy and
      simplified product ion mass spectra were observed following FAIMS preselection
      and subsequent in-source CID of ions derived from pharmaceutical excipients,
      sufficiently close in m/z (17.7 ppm mass difference) that they could not be
      resolved by TOFMS alone. The FISCID-MS approach is also demonstrated for the
      qualitative and quantitative analysis of mixtures of peptides with FAIMS used to
      filter out unrelated precursor ions thereby simplifying the resulting product ion
      mass spectra. Liquid chromatography combined with FISCID-MS was applied to the
      analysis of coeluting model peptides and tryptic peptides derived from human
      plasma proteins, allowing precursor ion selection and CID to yield product ion
      data suitable for peptide identification via database searching. The potential of
      FISCID-MS for the quantitative determination of a model peptide spiked into human
      plasma in the range of 0.45-9.0 MUg/mL is demonstrated, showing good
      reproducibility (%RSD < 14.6%) and linearity (R(2) > 0.99).

PMID- 22455621
TI  - Effects of dihydropyridine calcium channel blockers on oxidized low-density
      lipoprotein induced proliferation and oxidative stress of vascular smooth muscle
      cells.
AB  - BACKGROUND: Dihydropyridine calcium channel blockers (CCBs) are more effective in
      reducing carotid intima-media thickness (IMT) than other classes of
      antihypertensive drugs due to their vascular effects. However, the mechanism
      remains to be elucidated. FINDINGS: Ox-LDL induced HUVSMCs proliferation in a
      time- and dose-dependent manner. When pretreated with three CCBs before 50 MUg/ml
      ox-LDL stimulation, 30 MUM lacidipine and 3 MUM amlodipine exhibited 27% and 18%
      decrease of pro-proliferative effect induced by ox-LDL, whereas (S-)-amlodipine
      did not have any anti-proliferative effect. 30 MUM lacidipine inhibited about two
      thirds of the ox-LDL induced ROS production in HUVSMCs, whereas amlodipine and (S
      )-amlodipine did not have influence on ROS production. The MAPKs pathway
      inhibitors inhibited the ox-LDL induced proliferation of HUVSMCs. CONCLUSION: Our
      study has demonstrated that lipophilic CCBs, such as lacidipine may inhibit ox
      LDL induced proliferation and oxidative stress of VSMCs, and that the ROS-MAPKs
      pathway might be involved in the mechanism.

PMID- 22455623
TI  - Biosurfactant-protein mixtures: Quillaja Bark Saponin at water/air and water/oil
      interfaces in presence of beta-lactoglobulin.
AB  - The adsorption kinetics of mixtures of a biosurfactant Quillaja Bark Saponin
      (QBS) with a globular protein, beta-lactoglobulin (beta-LG) at the water/air and
      water/tetradecane interfaces was investigated by measuring dynamic interfacial
      tension with axisymmetric drop shape analysis (ADSA) and maximum bubble pressure
      (MBP) techniques. With bulk concentration of beta-LG fixed at 10(-7) M, the most
      pronounced synergistic effects in the rate of the QBS adsorption at both
      interfaces were observed at low biosurfactant concentrations (5 * 10(-7)-1 * 10(
      5) M). The synergistic effect due to a protein-biosurfactant complex formation is
      clearly noticeable, yet less pronounced than, e.g., previously studied
      QBS/lysozyme mixtures. The surface pressures attained at water/oil interface are
      higher than in the water/air system, although, at high biosurfactant/protein
      ratios, the presence of beta-LG decelerates adsorption of the QBS/beta-LG complex
      onto the water/tetradecane interface. In analogy to mixtures of synthetic
      surfactants with proteins, the adsorbed layer gets dominated by QBS at higher
      biosurfactant concentrations, although the presence of beta-LG affects the
      surface pressures attained even at QBS/beta-LG ratios as high as 10(4). The
      synergistic effects are much less noticeable in foamability and emulsion
      formation/stability, as probed by the modified Bikerman's and dynamic light
      scattering (DLS) techniques, respectively. 

PMID- 22455622
TI  - Genetically divergent methicillin-resistant Staphylococcus aureus and sec
      dependent mastitis of dairy goats in Taiwan.
AB  - BACKGROUND: Widespread in the environment, Staphylococcus spp. infect animals and
      humans as normal flora or pathogens. By extending our recent report of multi-drug
      resistant (MDR) S. aureus in dairy goats, this study investigated the
      staphylococcal infection and characterized the MDR-S. aureus and methicillin
      resistant S. aureus (MRSA) isolates collected from goats in 2008 to elucidate the
      appearance of MRSA in goats and the mastitis associated staphylococcus
      enterotoxin (SE) types. A total of 555 samples were collected from six goat parts
      and three environmental sources among four dairy goat farms in southern Taiwan.
      Coagulase-positive and negative Staphylococcus spp. (CPS and CNS, respectively)
      were also identified. Furthermore, predominant SE genes of nine enterotoxin genes
      sea through sej along with antimicrobial resistance and genetic variations were
      determined. RESULTS: In total, 137 staphylococcal strains were identified and
      found predominantly in milk, and in the vagina, anus, and nasal cavity. The most
      prevalent species was S. lentus, followed by S. aureus, S. epidermidis, and S.
      xylosus. Enterotoxin genes were not identified in any CNS isolates, however sec
      and see were identified only in S. aureus associated with mastitis in goat. In
      compared to the isolates from 2006 to 2007, 27 S. aureus isolates from 2008 were
      found to be more resistant to ampicillin, cephalothin, oxacillin,
      oxytetracycline, penicillin G, and tetracycline. Eleven MRSA isolates were
      identified and belonged to SCCmec type III (nine isolates) as the major type and
      SCCmec type II (two isolates). These MRSA isolates revealed pulse-field gel
      electrophoresis (PFGE) pattern A (five isolates), C (one isolate), and D (one
      isolate) of human isolates. The other two isolates without pulsotypes belonged to
      ST59. CONCLUSION: The prevalence and infection sites of CNS differed from those
      of CPS. Genetic analyses indicated that genetic divergence, possible zoonotic
      transfer of MRSA, and the involvement of sec as important virulence factors for
      of S. aureus that lead to mastitis in goats.

PMID- 22455624
TI  - Dual-lifetime referencing (DLR): a powerful method for on-line measurement of
      internal pH in carrier-bound immobilized biocatalysts.
AB  - BACKGROUND: Industrial-scale biocatalytic synthesis of fine chemicals occurs
      preferentially as continuous processes employing immobilized enzymes on insoluble
      porous carriers. Diffusional effects in these systems often create substrate and
      product concentration gradients between bulk liquid and the carrier. Moreover,
      some widely-used biotransformation processes induce changes in proton
      concentration. Unlike the bulk pH, which is usually controlled at a suitable
      value, the intraparticle pH of immobilized enzymes may deviate significantly from
      its activity and stability optima. The magnitude of the resulting pH gradient
      depends on the ratio of characteristic times for enzymatic reaction and on mass
      transfer (the latter is strongly influenced by geometrical features of the porous
      carrier). Design and selection of optimally performing enzyme immobilizates would
      therefore benefit largely from experimental studies of the intraparticle pH
      environment. Here, a simple and non-invasive method based on dual-lifetime
      referencing (DLR) for pH determination in immobilized enzymes is introduced. The
      technique is applicable to other systems in which particles are kept in
      suspension by agitation. RESULTS: The DLR method employs fluorescein as pH
      sensitive luminophore and Ru(II) tris(4,7-diphenyl-1,10-phenantroline),
      abbreviated Ru(dpp), as the reference luminophore. Luminescence intensities of
      the two luminophores are converted into an overall phase shift suitable for pH
      determination in the range 5.0-8.0. Sepabeads EC-EP were labeled by physically
      incorporating lipophilic variants of the two luminophores into their polymeric
      matrix. These beads were employed as carriers for immobilization of cephalosporin
      C amidase (a model enzyme of industrial relevance). The luminophores did not
      interfere with the enzyme immobilization characteristics. Analytical
      intraparticle pH determination was optimized for sensitivity, reproducibility and
      signal stability under conditions of continuous measurement. During hydrolysis of
      cephalosporin C by the immobilizate in a stirred reactor with bulk pH maintained
      at 8.0, the intraparticle pH dropped initially by about 1 pH unit and gradually
      returned to the bulk pH, reflecting the depletion of substrate from solution.
      These results support measurement of intraparticle pH as a potential analytical
      processing tool for proton-forming/consuming biotransformations catalyzed by
      carrier-bound immobilized enzymes. CONCLUSIONS: Fluorescein and Ru(dpp)
      constitute a useful pair of luminophores in by DLR-based intraparticle pH
      monitoring. The pH range accessible by the chosen DLR system overlaps favorably
      with the pH ranges at which enzymes are optimally active and stable. DLR removes
      the restriction of working with static immobilized enzyme particles, enabling
      suspensions of particles to be characterized also. The pH gradient developed
      between particle and bulk liquid during reaction steady state is an important
      carrier selection parameter for enzyme immobilization and optimization of
      biocatalytic conversion processes. Determination of this parameter was rendered
      possible by the presented DLR method.

PMID- 22455625
TI  - Controlled synthesis of topological insulator nanoplate arrays on mica.
AB  - The orientation- and position-controlled synthesis of single-crystal topological
      insulator (Bi(2)Se(3) and Bi(2)Te(3)) nanoplate arrays on mica substrates was
      achieved using van der Waals epitaxy. Individual ultrathin nanoplates with the
      lateral dimension up to ~0.1 mm or uniform thickness down to 1-2 nm were
      produced. Single-Dirac-cone surface states of nanoplate aggregates were confirmed
      by angle-resolved photoemission spectroscopy measurements. The large-grain-size,
      single-crystal nanoplate arrays grown on mica can act as facile platforms for a
      combination of spectroscopy and in situ transport measurements, which may open up
      new avenues for studying exotic physical phenomena, surface chemical reactions,
      and modification in topological insulators.

PMID- 22455626
TI  - Impact of aerobic exercise trials with varied intensity patterns on perceptions
      of effort: an evaluation of predicted, in-task, and session exertion.
AB  - Perceptions of effort provide a sense of momentary exertion during exercise, but
      may have value when considered prior to and after exercise. The purpose of the
      present study was to determine the relationship between perceived exertion
      assessed before, during, and after trials of aerobic exercise fixed for total
      work but varied on intensity patterns. Twenty participants completed five trials
      of treadmill exercise that included planned intensity variations every 10 minutes
      to result in the same total work. Perceived exertion was taken before, during,
      and after exercise. Analyses confirmed each trial was similar in terms of average
      speed and heart rate (P > 0.05). Predicted and session exertion results indicated
      that the steady exercise bout was perceived as easier than many trials of varied
      speed (P < 0.05). Trials including an intense segment in the middle or end of the
      session were perceived as more difficult than sessions that varied intensity
      otherwise or remained constant. Similarly, trials that remained constant during
      the 30-minute period were perceived as less aversive than most other trials.
      These findings suggest that exercise sessions involving a steady intensity
      throughout are viewed as less taxing than sessions with variable intensity,
      especially when compared to sessions that conclude with a higher intensity
      finish.

PMID- 22455627
TI  - Preparation of trifluoromethyl-substituted aziridines with in situ generated
      CF3CHN2.
AB  - Direct access to trifluoromethyl-substituted aziridines through the use of a
      protocol in which trifluoromethyl diazomethane is generated in situ and
      subsequently undergoes addition to activated imines is reported.

PMID- 22455628
TI  - [The current situation of diagnosis and treatment of chronic cough in Chinese
      children].

PMID- 22455629
TI  - [Prospective multicenter clinical study on the causes constituents ratio of
      chronic cough in Chinese children].
AB  - OBJECTIVE: To understand the causes of chronic cough in children in China and the
      composition ratio of the distribution and to promote the standardization and
      normalization of its treatment. METHOD: According to the 2008 Guidelines of
      diagnosis and treatment of chronic cough in children that were formulated by The
      Subspecialty Group of Respiratory Diseases, The Society of Pediatrics, Chinese
      Medical Association and the editorial board of Chinese Journal of Pediatrics we
      designed the questionnaire of the causes of chronic cough in children and
      organized 29 hospitals in 19 provinces, municipalities and autonomous regions to
      enroll cases with chronic cough and completed 3-month follow-up. The data were
      statistically analyzed and the causes constituents ratio of chronic cough was
      obtained. RESULT: Of 4582 cases, 4529 were eligible (the passing rate of 98.8%).
      The leading 3 causes were cough variant asthma (CVA) in 1900 cases (41.95%),
      upper airway cough syndrome (UACS) in 1119 cases (24.71%), respiratory infections
      and post-infectious cough (PIC) in 984 cases (21.73%). Gastroesophageal reflux
      cough (GERC) found in 28 cases (accounting for 0.62%); other causes were 498
      cases (11%), in which 387 cases (8.54%) had multiple etiologies. The leading
      cause in UACS associated with CVA, which accounted for 50.13%, followed by PIC
      with UACS accounting for 26.10%. The total correct diagnosis rate was 18.83%.
      Among different causes in different gender and age distribution were
      significantly different. CONCLUSION: The main causes of chronic cough in Chinese
      children are CVA, UACS, PIC and other causes. We should pay attention to the
      causes and cases of unknown etiology. Children in different age and gender groups
      have different constitute ratio of cause of chronic cough.

PMID- 22455630
TI  - [Effects of obstructive sleep apnea hypopnea syndrome in children on multiple
      systems].
AB  - OBJECTIVE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may cause serious
      morbidities, such as systemic hypertension, diabetes, and cor pulmonale. However,
      currently no many reports on study of OSAHS in children are available. This study
      aimed to explore the effects of OSAHS on children's multiple systems. METHOD: A
      total of 89 cases of children who came to the Sleep Treatment Center in the
      authors' hospital from March 2009 to December 2010 with snoring were tested with
      overnight polysomnography (PSG). They were classified into mild OSAHS group (n =
      59, mean age of 5.71, SD = 2.46) and moderate to severe group (n = 30, mean age
      of 5.30, SD = 2.73) based on the PSG results, and 100 healthy children were
      selected as the control group (n = 100, mean age of 6 years, SD = 2.98). Data
      including height, weight, body mass index and blood pressure, peripheral blood
      routine, blood lipids, glucose and insulin, electrocardiogram and
      echocardiography were collected. Patients' adenoid face and abnormal occlusion
      were also recorded. Comparisons of the data were made among those groups. RESULT:
      Mild OSAHS and moderate to severe group had significantly higher prevalence of
      adenoid face (23.7%, 26.7%), and abnormal occlusion (74.6%, 60.0%) than that in
      control group (0, 40%) (P < 0.05). There were no significant differences in terms
      of BMI between the OSAHS group and the control group, but the weight (kg) and
      height (cm) in the mild OSAHS group (23.3 +/- 10.1, 114.9 +/- 16.2) and moderate
      to severe group (21.9 +/- 8.4, 110.8 +/- 13.3) were lower than those of the
      control group (31.8 +/- 10.1, 136.1 +/- 15.1) (all P < 0.05). Compared with the
      control group, the level of HDL-C (mmol/L)and insulin (mU/L) in moderate and
      severe group decreased [(1.20 +/- 0.30) vs. (1.40 +/- 0.27), 2.79 (0.84 - 16.16)
      vs. 4.92 (0.76 - 16.80), P < 0.05], while the LDL-C (mmol/L) increased [(2.61 +/-
      0.75) vs. (2.32 +/- 0.62), P < 0.05]. The red blood cell counts (* 10(12)/L) and
      the blood platelet counts (* 10(9)/L) in the mild OSAHS (4.93 +/- 0.37, 292.92 +/
      75.64) and moderate and severe OSAHS group (5.23 +/- 0.22, 292.50 +/- 63.05)
      were significantly higher in contrast to the control group (4.70 +/- 0.31, 255.60
      +/- 69.12) (all P < 0.05), systolic blood pressure (mmHg) in mild group (98.54 +/
      10.44) and moderate to severe group (99.13 +/- 19.13) was significantly higher
      compared to control group (87.88 +/- 11.37), and the heart rate (beats/min) in
      moderate to severe group (94.43 +/- 10.64) was higher than those in control group
      (87.12 +/- 16.20) (all P < 0.05). The mild OSAHS and moderate and severe OSAHS
      group had decreased right ventricular internal diameter [(14.24 +/- 1.64) mm,
      (13.17 +/- 2.07) mm ], increased main pulmonary artery diameter [(17.05 +/- 3.33)
      mm, (16.33 +/- 3.14) mm] and the thickness of right ventricular wall [(3.43 +/-
      0.26) mm, (3.57 +/- 0.20) mm] compared to control group [ (16.10 +/- 2.96) mm,
      (14.11 +/- 2.52) mm, (3.32 +/- 0.25) mm] (all P < 0.05). CONCLUSION: OSAHS in
      children may be associated with craniofacial malformations, and may contribute to
      slow growth and development, elevated blood viscosity and blood pressure,
      metabolic abnormalities, and change cardiac structure.

PMID- 22455631
TI  - [Clinical characteristics of bronchiolitis obliterans in pediatric patients].
AB  - OBJECTIVE: To analyze the clinical characteristics, image findings, laboratory
      examination, the therapeutic methods and clinical outcomes of bronchiolitis
      obliterans (BO) in pediatric patients. METHOD: Twenty-six pediatric patients with
      BO were reported. All data were collected from cases who were hospitalized in the
      Department of Pediatrics, First Affiliated Hospital of Guangzhou Medical College
      from June 1(st), 2009 to the April 30(th), 2011, and infectious agents, clinical
      manifestations, risk factors, changes in imageology, laboratory examination,
      therapeutic methods and treatment responses were analyzed. RESULT: The ranges of
      age at onset was 4.5 months-8 years in 26 cases (18 boys and 8 girls). The course
      of disease was (6.2 +/- 3.5) months. The period of followed-up ranged from 2 to
      24 months. The common clinical characteristics were persistent wheezing of
      different severity (26 cases, 100%), cough (24 cases, 92%), intolerance to
      exercise (22 cases, 85%), short of breath (21 cases, 81%), retraction (20 cases,
      77%), wheezy phlegm (16 cases, 62%), keeping with crackles (10 cases, 38%),
      cyanosis around the mouth (3 cases, 12%) and no clubbed fingers (toes). In 18
      cases the etiology was detected, mycoplasma (11 cases, 42%), respiratory
      syncytial virus (4 cases, 15%), parainfluenza virus (2 cases, 8%), influenza
      virus A (2 cases, 8%) and influenza virus B (2 cases, 8%), human bocavirus (HBoV)
      (1 case, 4%). There were 8 cases (31%) with combined infection. Chest X-ray in 10
      cases indicated changes suggestive of bronchopneumonia (38%), in only 1 case
      there was an image of interstitial pneumonia disease (4%). All the patients were
      diagnosed by high-resolution computerized tomography (HRCT). All cases were
      demonstrated to have air retention, poor blood perfusion in lung, just like
      "Westemark sign" with HRCT. In 19 cases antineutrophil cytoplasmic antibody
      (ANCA) was determined and 10 patients (53%) were positive for P-ANCA, and 8 cases
      (42%) were positive for C-ANCA. All patients received oral corticosteroid and low
      doses azithromycin. In 13 cases (50%) the treatment effectively reduced the
      severity of disease and the frequency of cough and wheezing. The average number
      of days for symptom improvement was (7.1 +/- 4.8) days. CONCLUSION: Respiratory
      infection plays an important role in BO in children. The chronic and persistent
      wheezing, cough, intolerance to exercises, short breath, retraction were the main
      clinical manifestations. But these symptoms are non-specific. Chest X-ray can not
      provide enough information for diagnosis. Classical "Westemark sign" with HRCT is
      an important sign. ANCA with a high positive rate (approximately 50%) suppose
      immuno-lesion in BO. Oral corticosteroid and methotrexate may relieve clinical
      symptoms.

PMID- 22455632
TI  - [Constructing and evaluating children asthma family management system].

PMID- 22455633
TI  - [Advances in studies on brain injuries associated with congenital heart disease].

PMID- 22455634
TI  - [Detection of genetic defect within ABCA3 from newborns with respiratory distress
      syndrome].
AB  - OBJECTIVE: To detect possible relationship between genetic defect within the gene
      encoding member A3 of the ATP Binding Cassette family (ABCA3) and neonatal
      respiratory distress syndrome (NRDS), thus to understand the genetic mechanisms
      of NRDS in Han ethnic group. METHOD: The clinical data of 11 cases with NRDS
      hospitalized in neonatal intensive care unit was investigated. Blood samples were
      collected from 11 cases with NRDS and 97 unassociated normal individuals.
      Polymerase chain reaction (PCR) and DNA direct sequencing were performed to
      screen all exons and their flanking introns of ABCA3 gene for mutation analysis
      in 11 cases with NRDS. If a new missense variation was identified, single strand
      conformation polymorphism analysis was performed in 97 healthy controls. Lung
      tissue sample from a case who died 12 hours after birth was examined with light
      microscopy and electron microscopy. RESULT: Three missense genetic variants in
      exons, which include c. 2169 G > A (p.M723I), c. 1010 T > G (p.V337G), c. 4972 A
      > G (p.S1658G), one splice junction site variation (Exon 30 + 2 T/G), several
      unreported polymorphism sites [213 C > T(p.F71F), exon 21 + 34C/T] and reported
      polymorphism site (p.F353F) were identified on ABCA3 gene coding region in 11
      case. The homozygous variation (c.2169G > A), which was in exon 17 and causes an
      M723I amino acid change, was found in the case who died 13 hours after birth, but
      not detected in 97 controls, indicating that this variation is indeed a mutation
      and not a polymorphism. In the case carrying c.2169G > A, ultrastructural
      examination of the alveolar type II cells with electron microscopy demonstrated
      abnormally small and dense lamellar body with eccentrically distributed electron
      dense substance. CONCLUSION: Genetic variants within ABCA3 may be the genetic
      cause of or a contributor to some unexplained refractory NRDS. Identification of
      ABCA3 genetic variant in NRDS infants is important to establish appropriate
      management and evaluation of treatment options, as well as to offer genetic
      counseling and prenatal diagnosis.

PMID- 22455635
TI  - [A modified Calgary syncope syndrome score in the differential diagnosis between
      cardiac syncope and vasovagal syncope].
AB  - OBJECTIVE: This study aimed at analyzing the usefulness of a modified Calgary
      Syncope Syndrome Score in the differential diagnosis between cardiac syncope (CS)
      and vasovagal syncope (VVS) in children through a large sample clinical study.
      METHOD: Totally 189 children [112 males, 77 females, aged 2 - 18 yrs, mean age
      (12.4 +/- 3.1) yrs] with CS and VVS who were at the syncope clinic or admitted to
      the Department of Pediatrics, Peking University First Hospital from August 2002
      to April 2011 were included in the study. The diagnosis was analyzed by a
      modified Calgary Syncope Syndrome Score and receiver operating characteristic
      (ROC) curve was used to explore the predictive value of different Calgary Syncope
      Syndrome Scores in differential diagnosis between CS and VVS. RESULT: There were
      significant differences in the score between CS [-5.00(-7, 1)] and VVS [1(-4, 6)]
      (P < 0.01). When the score was <= -2.5, the sensitivity and specificity of the
      differential diagnosis between CS and VVS were 95.4% and 67.7%, respectively.
      Since the modified Calgary Syncope Syndrome Score was integer number, CS should
      be considered when the score was less than -3. CONCLUSION: The modified Calgary
      Syncope Syndrome Score might be used as an initial diagnostic method in
      differential diagnosis between CS and VVS, based on the history of the patients.

PMID- 22455636
TI  - [Effects of different arterial oxygen partial pressures on serum protein S100beta
      and neuron specific enolase during cardiopulmonary bypass in infants with
      cyanotic congenital heart disease].
AB  - OBJECTIVE: A prospective study was conducted to probe into the relationship
      between arterial oxygen partial pressure (PaO2) and brain injury during
      cardiopulmonary bypass (CPB) in infants with cyanotic congenital heart disease
      (CHD). METHOD: Enrolled in the study were 45 cyanotic infants, who were less than
      three years old and underwent corrective cardiac surgery from August 1(st), 2010
      to January 31(st), 2011 at Guangdong General Hospital. All the infants had a
      pulse oxygen saturation (SpO2) lower than 85% and were randomly allocated into
      three groups by a specific computer program. In controlled group 1 (G1 group),
      PaO2 levels were controlled at 80 - 120 mm Hg (1 mm Hg = 0.133 kPa) during CPB;
      in controlled group 2 (G2 group), PaO2 levels at 120 - 200 mm Hg during CPB;
      while in uncontrolled group (G3 group), PaO2 levels were at 200 - 400 mm Hg
      during CPB. Blood samples were collected just before starting CPB, at the end of
      CPB, and at 3 h, 5 h, and 24 h after CPB (T1, T2, T3, T4, T5) for the
      determination of serum concentrations of protein S100beta, neuron specific
      enolase (NSE), and adrenomedullin (ADM) by ELISA. RESULT: Protein S100beta rose
      significantly after starting CPB. In group G3, it reached a peak of (699 +/- 139)
      ng/L by the end of CPB, significantly higher than those in groups G1 and G2 [(528
      +/- 163) ng/L and (585 +/- 155) ng/L], and was positively correlated with PaO2
      levels (r = 0.526, P < 0.01). NSE levels of group G1 were continuously rising
      after starting CPB and reached significantly high levels at 3 h or 5 h after CPB
      [(12.2 +/- 3.4) ug/L and (12.3 +/- 3.7) ug/L], while those of group G2 rose
      significantly during CPB [(10.9 +/- 4.8) ug/L] and even higher at 3 h or 5 h
      after CPB [(12.6 +/- 5.1) ug/L and (13.2 +/- 5.4) ug/L]. NSE levels of group G3
      rose significantly during CPB and maintained at a high level [(12.2 +/- 5.7)
      ug/L] afterwards. There was no significant difference in serum ADM concentrations
      among different time points in each group and among these three groups. All the
      infants were discharged from the hospital without any obvious nervous symptom and
      sign. CONCLUSION: High PaO2 during CPB in infants with CHD might cause an
      increase of serum protein S100beta and NSE, indicating that brain injury might
      become worse with a higher PaO2 and might be positively correlated with PaO2
      during CPB.

PMID- 22455637
TI  - [Application of succinylacetone levels measurement in the blood and urine in the
      diagnosis of tyrosinemia type 1].
AB  - OBJECTIVE: To establish the diagnostic method of tyrosinemia type 1 and evaluate
      its value, the succinylacetone levels in the blood of suspected patients with
      tyrosinemia were tested by tandem mass spectrometry, and the succinylacetone in
      the urine was tested by gas chromatography-mass spectrometry. METHOD: A total of
      190 patients suspected of having tyrosinemia, were tested by tandem mass
      spectrometry for measurement of the level of succinylacetone in the blood, and
      detected by gas chromatography-mass spectrometry for measurement of the level of
      succinylacetone and organic acid in the urine. The method of measuring the level
      of succinylacetone in blood by tandem mass spectrometry as follows: After the
      diameter of 3 mm dry blood spots were punched into wells of 96-well plate, 100 ul
      80% acetonitrile were added into each well, which contained hydrazine monohydrate
      and the internal standard of succinylacetone. The supernatant fluid were
      transferred to another 96-well plate and dried under heated nitrogen, after the
      plate was incubated for 30 min at 65 degrees C. The residual hydrazine reagent
      was removed by addition of 100 ul methanol to each well and evaporated under
      heated nitrogen. The mobile phase (80% acetonitrile) was added to each well and
      20 ul samples were tested by tandem mass spectrometry. The diagnostic terms were
      the clinical manifestation and the high level of succinylacetone in both blood
      and urine. RESULT: Eleven patients were diagnosed as tyrosinemia type 1, with 9
      males and 2 females. Their ages ranged from 2 months to 6 years. The
      succinylacetone levels in the blood of the patients were remarkably increased
      (7.26-31.09 umol/L), with an average of (14.2 +/- 7.8)umol/L. Seven patients were
      tested for the level of succinylacetone in the urine by gas chromatography-mass
      spectrometry, and 4 were positive and 3 negative. Their tyrosine levels in the
      blood were 190-543 umol/L(Normal: 20 - 100 umol/L), with an average of (327.3 +/-
      125.8) umol/L. All the patients presented the symptoms of hepatomegaly. Among
      them, 9 patients died and 2 patients were improved after treatment. CONCLUSION:
      The higher levels of succinylacetone in the blood or urine is a remarkable
      evidence for the diagnosis of tyrosinemia type 1. Determination of
      succinylacetone in the dry blood spots using tandem mass spectrometry was a good
      method for diagnosis of tyrosinemia type 1. To test succinylacetone in urine by
      gas chromatography-mass spectrometry may yield a false-negative result for
      tyrosinemia type 1.

PMID- 22455638
TI  - [Analysis of arterial spin labeling in 33 patients with hypoxic ischemic
      encephalopathy].
AB  - OBJECTIVES: To evaluate the diagnostic value of arterial spin labeling (ASL)
      technology in newborns with hypoxic ischemic encephalopathy (HIE). METHOD: Seven
      full-term newborn infants without any history of asphyxia and other nervous
      system diseases were selected as the control and 33 full-term newborn infants
      were assigned into HIE group. The patients in HIE group were further divided into
      three subgroups (19 cases of mild, 6 cases of moderate and 8 cases of severe HIE)
      based on their clinical diagnosis. The control group and HIE group were examined
      with GE Signa EXCITE HD 3.0T superconducting MRI scanner with a head phase array
      coil. Both groups were scanned with conventional axial MRI (T1FLAIR, T2WI and
      T2FLAIR), 1HMRS (PRESS sequence) and ASL (FAIR). Original images of 1HMRS and ASL
      were processed by Functool software of ADW 4.3 workstation. ASL perfusion images
      were observed and the signal intensity values of the region of interest
      (bilateral gray, white matter and basal ganglia) of the two groups were
      quantitatively measured, and mean value were calculated and compared between
      groups. Statistical analysis was performed with SPSS 13.0 software, and
      statistically significant difference was set at P < 0.05. RESULT: The perfusion
      images of two groups were obtained perfectly. The signal intensity values of
      bilateral gray, white matter and basal ganglia of control group were 125.34 +/-
      11.76, 73.42 +/- 11.67 and 173.65 +/- 15.49, respectively and there was a
      statistically significant difference between the different areas. The signal
      intensity values of bilateral gray, white matter and basal ganglia of HIE group
      were 153.47 +/- 11.72, 71.35 +/- 10.37 and 217.13 +/- 12.51, respectively. There
      was a statistically significant difference (P < 0.05) in the average signal
      intensity value of gray matter and basal ganglia, but there were no statistically
      significant difference (P > 0.05) in white matter between the two groups.
      CONCLUSION: ASL Perfusion technique can assess HIE comprehensively and
      accurately. Furthermore, it can evaluate the brain damage of hypoxic ischemia.
      The results provide a strong basis for clinical treatment.

PMID- 22455639
TI  - [Effect of nitric oxide on the preterm neonatal rabbit ductus arteriosus
      cystathionine-gamma-lyase/hydrogen sulfide pathway].
AB  - OBJECTIVE: To investigate the impact of sodium nitroprusside (a nitric oxide
      donor) in the ductus arteriosus in preterm rabbits on hydrogen sulfide (H(2)S)
      cystathionine-gamma-lyase (CSE) system. METHODS: For 16 Japanese white rabbits
      pregnant for 21 days were randomly divided into four groups, each of the
      following groups had 4 rabbits: control group, intraperitoneal injection of
      sodium nitroprusside 1 mg/kg, 2.5 mg/kg, and 5.0 mg/kg groups. The rabbits in
      control group had a peritoneal puncture with a simple hollow needle, and those in
      the other groups were given corresponding dose of intraperitoneal injection of
      sodium nitroprusside at gestational age 23 and 25 days, respectively. At
      gestational age 26 days the fetuses of the pregnant rabbits were removed
      surgically, and 28 fetal rabbits were obtained from the control group, 27 from
      the sodium nitroprusside small dose group, 29 from the medium dose group, and 26
      from the large dose group. The fetal heart blood sample of 1 ml was taken from
      each fetus, and immediately after sampling the arterial ductal tissues were
      dissected. Fetal rabbit plasma proteins hydrogen sulfide content was determined
      by using de-protein method, and real time quantitative RT-PCR was used for
      determination of arterial tissue CSE gene and western-blotting was used for
      measuring protein expression of CSE. RESULTS: In control group hydrogen sulfide
      content of fetal rabbits plasma (55.68 +/- 6.57) umol/L and arterial tissue CSE
      mRNA expression was 1.07 +/- 4.12; the parameters in intraperitoneal injection of
      sodium nitroprusside group 1 mg/kg were (60.02 +/- 6.09) umol/L and 3.46 +/-
      0.18; in intraperitoneal injection of sodium nitroprusside group 2.5 mg/kg, were
      (64.71 +/- 7.12) umol/L and 10.95 +/- 0.22; and in intraperitoneal injection of
      sodium nitroprusside group 1 mg/kg were (70.63 +/- 8.07) umol/L and 19.56 +/-
      0.17. Comparison between small dose group and control group, medium dose group
      and small dose group, high dose group and medium dose group showed that the above
      data were significantly different P < 0.05, with the injection of sodium
      nitroprusside CSE protein expression increased gradually with increasing doses.
      CONCLUSION: Sodium nitroprusside showed an enhancing effect on preterm CSE-H(2)S
      system in rabbit ductus arteriosus in a certain range of concentration in a dose
      dependent manner.

PMID- 22455640
TI  - [Effects of Matrigel on expression of focal adhesion kinase and on proliferation
      and apoptosis of alveolar epithelial cell II of premature rat exposed to
      hyperoxia].
AB  - OBJECTIVE: To investigate the effects of Matrigel on expression of focal adhesion
      kinase and on proliferation and apoptosis of alveolar epithelial cell II of
      premature rat exposed to hyperoxia. METHODS: The primary premature rat AECII
      (gestation 19 d) were cultured in vitro. For establishing hyperoxia-exposed cell
      model, purified AECII were cultured for 12 hours after culture flasks were filled
      with 95% oxygen-5% CO2 at 5 L/min, and then sealed for 12 hours. DNA content,
      phosphor and total protein of FAK were detected by semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and Western blotting
      respectively after 12 hours of air or hyperoxia exposure in the presence or
      absence of Matrigel. To investigate the relationship between FAK activated and
      proliferation or apoptosis of type II alveolar epithelial cells, levels of
      proliferation and apoptosis of AECII were measured by immunohistochemical assay
      of proliferating cell nuclear antigen (PCNA) and TUNEL method respectively.
      RESULTS: FAK and FAK-Tyr(397) activity of AECII on Matrigel-coated substrate
      increased: compared with air group, the expression of PCNA decreased and
      apoptotic index increased markedly in hyperoxia group (0.1498 +/- 0.009 vs.
      0.0953 +/- 0.006, P < 0.05; 1.232 +/- 0.6 vs. 13.40 +/- 3.2, P < 0.01), but the
      expression of PCNA of AECII on Matrigel-coated substrate increased significantly
      (0.1498 +/- 0.009 vs. 0.1921 +/- 0.008, P < 0.01) and apoptotic index did not
      change. The expression of PCNA increased significantly (0.0953 +/- 0.006 vs.
      0.1125 +/- 0.012, P < 0.05) and apoptotic index decreased markedly in hyperoxia +
      Matrigel group as compared with hyperoxia group (13.40 +/- 3.2 vs. 7.641 +/- 1.6,
      P < 0.05). CONCLUSION: Hyperoxia decreased the level of FAK and FAK-Tyr(397) in
      AECII, which may be a contributory mechanism of impaired proliferation and
      apoptosis of AECII in hyperoxia induced lung injury in premature rat. Matrigel
      could inhibit apoptosis and promote proliferation of AECII resulted from
      hyperoxia in vitro. Matrigel may play a protective role in hyperoxia-induced lung
      injury partly due to activated FAK.

PMID- 22455641
TI  - [Isolated pulmonary Langerhans cell histiocytosis in a two-year-old child: case
      report and literature review].
AB  - OBJECTIVE: To improve the recognition of the clinical features and results of
      laboratory examination for isolated pulmonary Langerhans cell histiocytosis
      (PLCH) in children. METHOD: The information of one case with isolated PLCH was
      analyzed and reports of 11 cases with isolated PLCH were reviewed. RESULT: The
      patient we report is only 2 years old with 1 month of course of disease,
      manifesting with prominent pulmonary involvement: cough and short of breath; CT
      scan of the chest showed punctiform, nodular and reticular high density opacities
      involving all lobes of both lungs. Biopsy of the lung tissue showed expression of
      CD1a, CD68, S-100, consistent with the diagnosis of LCH. He received
      prednisolone, VP16 and Vindesine with good response. Ten of 11 cases of isolated
      PLCH reported before manifesting with cough and dyspnea, CT scan of the chest
      showed interstitial lung changes (5/8), cystic changes (5/8), small nodules (2/8)
      and pneumothorax (2/8). Langerhans cells were found in 9 cases on lung biopsy,
      part of biopsy lung tissues were stained with anti-CD1a, the alveolar lavage
      fluid of the other 2 cases were stained with S-100 and anti-CD1a. CONCLUSION:
      Isolated PLCH is rarely reported in children. It manifested with prominent
      pulmonary involvement: cough and short of breath, and CT scan of the chest showed
      interstitial lung changes, small nodules or cysts involving the lung, Langerhans
      cell could be found in lung biopsy, and the immunohistochemical staining in lung
      biopsy lung and alveolar lavage fluid stained with S-100 and anti-CD1a
      antibodies.

PMID- 22455642
TI  - [Clinical analysis of pulmonary embolism in a child with Mycoplasma pneumoniae
      pneumonia].
AB  - OBJECTIVE: To explore the essential points for diagnosis of pulmonary embolism in
      children with mycoplasma pneumonia. METHOD: Retrospective analysis of the
      clinical and laboratory data of a pediatric case who developed pulmonary embolism
      after mycoplasma pneumonia was performed for the key points for diagnosis.
      RESULT: A-six-year old boy was admitted with chief complaint of fever and cough
      for half a month, combined with chest pain and mild labored breath. Vital signs
      were stable. Breathing movement of the left side weakened and there was left
      lower lobe percussion dullness. Breath sound was found weakened in the left lung,
      and a few fine crackles were audible. The results of laboratory tests were as
      follows: mycoplasma antibody (IgM) 1:128, cold agglutinin test 1:1024, blood D
      dimer 14.81 mg/L; anticardiolipin antibody was positive; plasma protein C
      activity was 60% (normal range 70% - 130%). Pulmonary artery computed tomographic
      angiography revealed a mass opaque shadow in left lower lobe, the branch of left
      lower bronchial artery was partially obstructed. Echocardiography showed
      tricuspid valve mild regurgitation, estimated pulmonary pressure was 5.1 kPa.
      Single-photon emission computed tomography indicated that radioactivity
      distribution was apparently sparse in the dorsal segment, anterior basal segment,
      outer basal segment and inferior lingular segment of the left lung. The
      preliminary diagnosis on admission was mycoplasma pneumonia with pleural
      effusion, pulmonary embolism. Intravenous erythromycin combined with meropenem
      were administered. Anticoagulation therapy was initiated with low molecular
      weight heparin and then oral warfarin tablets. Pleural effusion disappeared soon,
      D dimer descended to 0.38 mg/L, and pulmonary artery pressure declined. After 3
      month follow-up, anti-cardiolipin antibody was negative, plasma protein C
      activity recovered, and lung lesions were absorbed. CONCLUSION: When mycoplasma
      pneumonia is accompanied by chest pain or dyspnea and there are bloody pleural
      effusion, pulmonary hypertension, positive antiphospholipid antibody and elevated
      D dimer, pulmonary embolism should be considered. Diagnosis could be clarified by
      the result of pulmonary artery computed tomographic angiography.

PMID- 22455643
TI  - [Introduction of guidelines on evaluation and treatment of Langerhans cell
      histiocytosis].

PMID- 22455644
TI  - [Summary of 16(th) national conference on pediatric cardiovascular diseases].

PMID- 22455645
TI  - The development and validation of an assay for the quantification of the P.
      chrysogenum allergen Pch52.
AB  - Penicillium chrysogenum clade 4, is a common mold on damp building materials. A
      capture ELISA assay for the major allergen from P. chrysogenum Pch52 has been
      developed and tested in house dust samples and potential cross-reactivity
      examined. Minimal cross-reactivity with other relevant indoor fungi was observed
      for the assay following thorough purification of the monoclonal and polyclonal
      antibodies. The limit of quantification for ELISA analysis of Pch52 in sieved
      house dust is comparable to other assays of other fungi. The LOQ for Pch52 was
      0.31 ng/mL in solution or 110 ng/g dust. The LOQ for Asp f1 and Alt a1 were 2.2
      ng/g and 17 ng/g, respectively. These results indicate this assay is suitable for
      the quantification of Pch52 in sieved house dust.

PMID- 22455646
TI  - [Radiation Protection in Orthodontics: relevant data].
AB  - For the past 30 years X-Ray images have effected a veritable revolution in
      medical practice. Using them practitioners cannot only make reliable and precise
      diagnoses when they begin a course of treatment but also accurately follow the
      progress of therapy. Orthodontics is one of the specialties that has benefited
      from the innovations in medical radiography. At the same time we have learned
      more about the risks that the use of ionizing radiation entails and are,
      accordingly, basing our radiological practice on the ALARA principle ("As Low As
      Reasonably Achievable"). Even though this concept is embodied in much national
      and European legislation, practitioners will enhance their daily use of radiology
      by acquiring an understanding of the scientific basis for ALARA.

PMID- 22455647
TI  - [Useful radiological techniques in orthodontics].
AB  - Specialists in dento-facial orthopedics have a large range of dental radiological
      techniques at their disposal to help them in their diagnostic and therapeutic
      procedures. Peri-apical, occlusal, panoramic, and cephalometric X-Rays are two
      dimensional techniques that orthodontists can complement, if necessary, with
      Multi slices CT scan or Cone Beam Computed Tomography. Orthodontists must apply
      and respect quality criteria for each type of film in order to derive the best
      information from every image and to avoid producing artifacts or false images
      that will reduce their diagnostic value and, accordingly, the service that they
      render to patients. Practitioners must be willing to spend the few moments it
      takes to position patients correctly in the radiological apparatus instead of
      taking multiple views to compensate for failing to scrupulously follow protocols
      of radiology.

PMID- 22455648
TI  - [Measurement errors in 2D cephalometrics].
AB  - The objective of this study is to analyze the influence that two parameters, the
      source-subject distance and the type of receptor, have on the precision of
      localization of the 19 most frequently employed cephalometric landmark points and
      then to analyze the repercussions of localization errors on cephalometric
      measurements. The correct use of profile cephalograms (norma lateralis) for
      clinical purposes depends essentially on the precision of the identification and
      localization of the different landmark points that are required for the
      elaboration of the various cephalometric analyses. For this study we asked 53
      orthodontists, selected at random, to identify 19 cephalometric points on
      standard profile or digitized films taken at distances of 1 m 50 or of 4 m. The
      results we obtained show no statistically significant differences in relation to
      the source-subject distance or to the type of receptor. Each cephalometric
      landmark presented a characteristic dispersion cloud; the most reliable points
      were primarily located on the median sagittal plane. The cephalometric
      measurements that demonstrated the greatest variability were associated with
      positions of the incisor apices, which makes their value doubtful in the
      establishment of treatment plans and in ongoing evaluations of treatment
      progress. For similar reasons, the worth of the Frankfort plane can be questioned
      when it is compared to other, much more reliable cranial reference planes
      especially S-Na.

PMID- 22455649
TI  - [Measurement errors in 3D cephalometrics: about the buccal cranio-facial
      analysis].
AB  - The development of three-dimensional radiological techniques generating low
      levels of radiation, like computed tomography and positron emission tomography
      with cone beam, has made it possible for orthodontists to utilize three
      dimensional cephalometry for certain complex clinical cases instead of
      conventional two dimensional imagery. Nevertheless, these new techniques rely on
      the identification of the most dependable anatomic landmarks. Fifteen randomly
      selected orthodontists were asked to identify on a computed tomography film 33
      points that were chosen for a buccal cranio-facial analysis because they have
      been traditionally recognized for their reproducibility. The results confirmed
      the high reliability level of the reference point vestibion that is related to
      the semi-circular canals. They showed, in the same way that conventional 2D
      cephalometry does, that each landmark presents a cloud and dispersion
      characteristic and that the most reliable landmarks are based on easily
      identifiable anatomic structures like foramens and osseous points.

PMID- 22455650
TI  - [Cervical vertebrae: Mandibular growth dynamism indicators?].
AB  - A study of mandibular growth maturation was performed on a population of 103
      patients during orthodontic treatment (69 girls and 34 boys) from 11 to 16 years,
      having initially a Class II skeletal discrepancy. The relationship between wrist
      maturation indices and the cervical vertebrae maturation was studied by Lamparski
      classification. Significant correlations were found between Bjork stages, MP3=,
      MP3 cap and MP3 U and respectively Lamparski stages as CVS 2, CVS 3-4 and CVS 5
      6. This retrospective longitudinal study identified three mandibular variables at
      three different maturation stages according to Bjork classification and to the
      six stages of Lamparski classification. The relationships between these different
      maturation stages and a quantitative mandibular response permit to estimate
      optimal time for our orthodontic therapy. The results indicate a significant
      increase in mandibular length between CVS 4 and CVS 5, suggesting the persistence
      of a condylar response to a stimulation therapy after CVS3 or CVS 4 stages (MP3
      cap). Mandibular growth seems to continue after MP3 U stage or CVS 5 stage.

PMID- 22455651
TI  - [Indications for radiography in orthodontics and dentofacial orthopedics].
AB  - The risks associated with the use of ionizing radiation are a constant concern
      not only for practitioners but also for legislators who have included this
      ethical rule in the Code of public safety. It proposes reduction of risks by
      insisting that all X-Rays be taken only when they accord with one of the
      fundamental principles of X-Ray protection: they must be justified by clear
      diagnostic need. In direct application of this principle the French government in
      2006 published a guide for the management of radiological and dental and
      stomatological examinations. However, this document dealt only slightly with
      orthodontics, a field in which the flourishing and burgeoning of radiological
      techniques made it urgent that regulations for use of X-Rays in orthodontics be
      brought up to date on an ongoing and permanent basis. The objective of this
      article is, accordingly, after presentation of a systematic and critical analysis
      of the lit erature, to propose up-to-date recommendations for proper taking of
      orthodontic X-Ray films.

PMID- 22455652
TI  - [Imaging of temporo-mandibular disorders].
AB  - Dominated for years by standard films (tomographic mouth open and mouth closed X
      rays, MRI) radiographs of the TMJ have progressively lost their usefulness to
      diagnosticians who have progressively increased their reliance on well codified
      clinical examinations, which suffice in a great majority of cases.The indications
      for and diagnostic worth of radiological studies and the impact they have on the
      management of TMJ disorders are today quite low especially when the high cost of
      procedures like MRI, computerized tomography, and CBCT is taken into account. In
      this article we discuss the various maladies that dentists might encounter and
      the situations in which radiological examinations are still indicated.

PMID- 22455653
TI  - [Digitized impressions: myth and daily reality].
AB  - The digitizing of impressions, or models made from them, opens, in the same way
      that digitized 3D X-rays did, new horizons for practitioners in the management
      for their offices, in their interactions with patients, and in their shared work
      with dental laboratories. Mastery of digitized models improves the efficiency and
      reinforces the quality of dental treatment through the new perspectives digital
      analyses provide. Finally the maintenance of records is greatly simplified in far
      less space while still respecting all pertinent legal requirements, thus assuring
      total suitability for all current regulations.

PMID- 22455654
TI  - The evolution of integration: innovations in clinical skills and ethics in first
      year medicine.
AB  - Critical self-reflection, medical ethics and clinical skills are each important
      components of medical education but are seldom linked in curriculum development.
      We developed a curriculum that builds on the existing integration of ethics
      education into the clinical skills course to more explicitly link these three
      skills. The curriculum builds on the existing integration of clinical skills and
      ethics in first year medicine. It refines the integration through scheduling
      changes; adds case studies that emphasise the social, economic and political
      context of our province's patient population; and introduces reflection on the
      "culture of medicine" as a way to have students articulate and understand their
      own values and moral decision making frameworks. This structured Clinical Skills
      course is a model for successfully integrating critical self-reflection,
      reflection on the political, economic and cultural contexts shaping health and
      healthcare, and moral decision making into clinical skills training.

PMID- 22455655
TI  - Teaching and training in breaking bad news at the Dutch medical schools: a
      comparison.
AB  - BACKGROUND: Physicians consider breaking bad news (BBN) a difficult task, and
      training is therefore necessary. There is much variety in what schools consider
      to be best practice and best timing for such training. This article discusses BBN
      programmes at the Dutch medical schools. We studied how students value their
      training and offer recommendations. METHODS: We developed two questionnaires to
      obtain programme information from course co-ordinators and student opinions about
      BBN-training. We compared student opinions right after BBN-training (T1) and
      towards the end of the medical curriculum (T2). RESULTS: BBN-programmes in Dutch
      medical schools vary in timing, models used and training methods. Overall,
      students are satisfied with the timing. They appreciate feedback by physicians
      and simulated patients most. At T2, some groups of students reported that BBN
      training had given them slightly less guidance than was reported by T1-students
      at the same institution. DISCUSSION: T2-students perhaps realised they had not
      received the amount of support they needed and may have shifted from being
      unconsciously incompetent to being consciously incompetent. RECOMMENDATIONS: We
      recommend: (a) longitudinal programmes with experiential skills-training sessions
      and clinical practice, (b) to involve simulated patients, physicians and
      psychologists in training programmes as well as practising physicians who
      supervise students during clinical work and (c) to ensure ongoing support and
      feedback in the clinical phase.

PMID- 22455656
TI  - The effect of raw vegetable and fruit intake on thyroid cancer risk among women:
      a case-control study in South Korea.
AB  - Thyroid cancer is the most common cancer among Korean women. However, there are
      few data on dietary factors related to thyroid cancer risk. The objective of the
      present study was to evaluate the association between raw vegetables and fruits
      intake and thyroid cancer in a case-control study. We included 111 histologically
      confirmed malignant thyroid cancer cases and 115 benign cases. Controls who did
      not have nodules in thyroid ultrasonography were matched to cases by age (+/- 2
      years). Food and nutrient intakes were estimated using a quantitative FFQ with
      121 items. Conditional logistic regression analysis was used to obtain OR and
      corresponding 95 % CI. The intake of total vegetables was not associated with
      malignant thyroid cancer, but inversely associated with benign cases. High raw
      vegetable intake was inversely associated with thyroid cancer risk both in
      malignant and benign cases (P for trend = 0.01 in both malignant and benign
      cases). Among fruits, persimmon intake had an inverse association with thyroid
      cancer risk in both malignant and benign cases (P for trend = 0.06 in malignant
      cases; P for trend = 0.01 in benign cases) and tangerine intake had an inverse
      association in malignant cases (P for trend = 0.03). The frequency of consumption
      of raw vegetables and persimmon also had a consistent inverse association in both
      malignant and benign cases. These results suggest that high consumption of raw
      vegetables, persimmons and tangerines may decrease thyroid cancer risk and help
      prevent early-stage thyroid cancer.

PMID- 22455657
TI  - Results of interferon alpha-2a therapy in patients with Behcet's disease.
AB  - PURPOSE: Corticosteroids, the main treatment option in acute attacks of ocular
      Behcet's disease (BD), are ineffective in preventing recurrent inflammation. Even
      combined therapy with systemic corticosteroids and azathioprine, cyclosporine,
      chlorambucil, or cyclophosphamide may be ineffective in controlling the disease
      in severe cases. We report our clinical experience with the efficacy and
      tolerability of interferon alpha-2a (IFN-alpha-2a) monotherapy in patients with
      Behcet uveitis refractory to conventional immunosuppressive agents. METHODS: We
      retrospectively analyzed the medical records of 12 Turkish Behcet patients who
      had been treated with IFN-alpha-2a between February 2009 and October 2011 because
      of severe uveitis refractory to traditional immunosuppressants. IFN-alpha-2a was
      initially administered at 4.5*10(6) IU/day subcutaneously; then, the dosage was
      tapered gradually depending on the clinical response. Previous immunosuppressive
      drugs such as systemic corticosteroids, azathioprine, and cyclosporine were
      stopped 1 day before the initiation of IFN-alpha-2a treatment. RESULTS: The mean
      duration of IFN-alpha-2a use was 13.3 months (range: 3-28 months). Eighty-three
      percent of patients with ocular BD achieved partial or complete response. Best
      corrected visual acuity improved or remained stable in all of patients. All
      patients experienced flu like symptoms responding to oral acetaminophen, hair
      loss was also developed in 7 of them (58%), and psoriatic skin rash was seen in 3
      patients (25%) during treatment with IFN-alpha-2a. No other side effects were
      observed. CONCLUSIONS: IFN-alpha-2a treatment is effective in Behcet uveitis
      refractory to traditional treatment regimens and provides significant improvement
      in visual prognosis.

PMID- 22455659
TI  - Dilution and the elusive baseline.
AB  - Knowledge of baseline conditions is critical for evaluating quantitatively the
      effect of human activities on environmental conditions, such as the impact of
      acid deposition. Efforts to restore ecosystems to prior, "pristine" condition
      require restoration targets, often based on some presumed or unknown baseline
      condition. Here, we show that rapid and relentless dilution of surface water
      chemistry is occurring in the White Mountains of New Hampshire, following decades
      of acid deposition. Extrapolating measured linear trends using a unique data set
      of up to 47 years, suggest that both precipitation and streamwater chemistry
      (r(2) >0.84 since 1985) in the Hubbard Brook Experimental Forest (HBEF) will
      approximate demineralized water within one to three decades. Because such dilute
      chemistry is unrealistic for surface waters, theoretical baseline compositions
      have been calculated for precipitation and streamwater: electrical conductivity
      of 3 and 5 MUS/cm, base cation concentrations of 7 and 39 MUeq/liter, acid
      neutralizing capacity values of <1 and 14 MUeq/liter, respectively; and pH 5.5
      for both. Significantly large and rapid dilution of surface waters to values even
      more dilute than proposed for Pre-Industrial Revolution (PIR) conditions has
      important ecological, biogeochemical and water resource management implications,
      such as for the success of early reproductive stages of aquatic organisms.

PMID- 22455658
TI  - Effect of topically applied epithelial sodium channel inhibitors on tear
      production in normal mice and in mice with induced aqueous tear deficiency.
AB  - PURPOSE: Dry eye syndromes affect a significant proportion of the population
      worldwide with reported prevalence ranging from 6% to more than 34%. Patients
      with dry eye can experience intense pain due to eye irritation, gritty/scratchy
      feeling in the eyes, blurry vision, and light sensitivity. Available treatments
      for dry eye syndromes remain mainly palliative. The purpose of the present study
      was to test the hypothesis that inhibiting sodium absorption via the epithelial
      sodium channel (ENaC) will increase ocular hydration in both normal as well as in
      animals with experimentally induced dry eye. METHODS: ENaC inhibitors were
      dissolved in an aqueous buffer that mimics the composition of tears and were
      applied topically to the ocular surface of isoflurane-anesthetized mice. The
      effect of ENaC inhibitors was compared with that of the secretagogue uridine
      triphosphate (UTP; 1%), a purinergic receptor agonist which was shown to increase
      tear volume in animals. Tear production was measured for 10 s using phenol red
      impregnated cotton threads. Fluorescein staining that assesses ocular surface
      damage was performed at baseline and then at days 1, 2, and 3 after the induction
      of dry eye in mice. RESULTS: Our data show that the inhibition of ENaC led to a
      time- and concentration-dependent increase in tear volume in normal mice. The
      effect of ENaC inhibition after a single application outperformed UTP, as it was
      long-lasting with tear volume still above baseline values 8 h postdosing. ENaC
      inhibition, which led to increased tear production, improved fluorescein scores
      in our dry eye model, when compared with nontreated or animals treated with
      buffer or UTP. CONCLUSION: We conclude that the inhibition of ENaC provides long
      lasting increases in ocular surface hydration and that ENaC blockers could
      provide an effective new therapy for chronic dry eye.

PMID- 22455660
TI  - Editorial: intrinsically disordered proteins: a focused look at fuzzy subjects.

PMID- 22455661
TI  - Urinary neutrophil gelatinase-associated lipocalin and L-type fatty acid binding
      protein as diagnostic markers of early acute kidney injury after liver
      transplantation.
AB  - OBJECTIVE: We examined the value of two potential novel urinary biomarkers,
      neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid binding
      protein (L-FABP), in diagnosing acute kidney injury (AKI) in liver transplant
      recipients. METHODS: NGAL and L-FABP in urinary sample from Twenty-five patients
      before surgery and at 2, 4, 6, 12, 24, 48, 72 and 120 h after the anhepatic phase
      were tested. Standard statistics were used along with receiver-operating
      characteristic (ROC) analysis to evaluate the diagnostic value of selected
      markers. RESULTS: Urinary NGAL was only slightly elevated at 2 h in the non-AKI
      group while rose and stayed high from 2-6 h in the AKI group. However, urinary L
      FABP rose transiently in both groups 2-120 h following surgery. The level of
      urinary NGAL presented differences at 2-6 h (p < 0.05) and urinary L-FABP at 4 h
      (p < 0.05) between AKI and non-AKI groups. ROC analysis showed that area under
      the curves (AUCs) of NGAL were 0.766, 0.773, and 0.773 at 2, 4 and 6 h
      respectively while 0.760 of L-FABP at 4 h. CONCLUSION: Urinary NGAL rather than L
      FABP appeared to be a sensitive and specific marker of AKI in liver transplant
      recipients.

PMID- 22455662
TI  - Plastic ingestion by the northern fulmar (Fulmarus glacialis) in Iceland.
AB  - In 2011, northern fulmars (Fulmarus glacialis) from Iceland were used to test the
      hypothesis that plastic debris decreases at northern latitudes in the Atlantic
      when moving away from major human centres of coastal and marine activities.
      Stomach analyses of Icelandic fulmars confirm that plastic pollution levels in
      the North Atlantic tend to decrease towards higher latitudes. Levels of pollution
      thus appear to link to regions of intense human coastal and marine activities,
      suggesting substantial current inputs in those areas.

PMID- 22455663
TI  - Toxicity effects of olive-mill wastewater on growth, photosynthesis and pollen
      morphology of spinach plants.
AB  - Olive mill-wastewater (OMW), a by-product of the olive oil extraction process,
      represents a significant environmental problem in Mediterranean areas. We studied
      the impact of OMW dilutions (1:10 and 1:20) on growth, photosynthesis, proline
      and sugar accumulation as well as on pollen morphology of spinach (Spinacia
      oleracea L.) plants, to evaluate the application of OMW dilutions as pretreatment
      technique, prior to land disposal. Biomass, height, total chlorophyll and leaf
      area of spinach declined progressively with decreasing OMW dilution. Since fatty
      acids and phenolic compounds (present in the OMW) are considered precursors in
      the polymerization of sporopollenin, we suggest that under OMW treatment spinach
      plants seem to 'direct' the excess of these substances in the production and
      formation of increased pollen grains. Proline did not accumulate under OMW
      stress, but decreased possible due to transport to pollens in response to
      increased demand to over-production of pollens. Both OMW dilutions resulted in a
      decreased efficiency of PSII functioning and an increased excitation pressure (1
      q(p)). It is concluded that, higher than 1:20 OMW dilutions should be used,
      and/or additional treatment should be applied before use of the OMW in the
      environment.

PMID- 22455664
TI  - The R337H mutation in TP53 and breast cancer in Brazil.
AB  - BACKGROUND: Germline mutations in p53 are associated with the Li-Fraumeni
      Syndrome which is characterized by childhood cancers, including pediatric adrenal
      cortical carcinomas and early onset breast cancer. The high incidence of adrenal
      cortical carcinomas in southern Brazil is mostly attributed to the R337H mutation
      in TP53. The relatively high population frequency of this mutation in southern
      Brazil, along with the clustering of early onset breast cancer in Li-Frameni
      families, suggests this mutation may also be a low-penetrance breast cancer
      susceptibility polymorphism. METHODS: We undertook this study to evaluate the
      frequency of the R337H mutation in breast cancer patients from Rio de Janeiro,
      Brazil. R337H mutation status was determined in 390 unselected breast cases and
      324 controls identified from clinics in Rio de Janeiro, Brazil using a PCR-based
      assay. RESULTS: Two of the breast cancer cases (0.5%) and none of the controls
      carried the mutation. Both cases had an early age at diagnosis (< 40 years old)
      and a family history of breast and other cancers. CONCLUSIONS: These data suggest
      genetic screening of young onset breast cancer patients should include testing
      for the R337H mutation.

PMID- 22455665
TI  - Carbonyl-reactive tandem mass tags for the proteome-wide quantification of N
      linked glycans.
AB  - N-Linked protein glycosylation is one of the most prevalent post-translational
      modifications and is involved in essential cellular functions such as cell-cell
      interactions and cellular recognition as well as in chronic diseases. In this
      study, we explored stable isotope labeled carbonyl-reactive tandem mass tags
      (glyco-TMTs) as a novel approach for the quantification of N-linked glycans.
      Glyco-TMTs bearing hydrazide- and aminooxy-functionalized groups were compared
      for glycan reducing end derivatization efficiency and quantification merits.
      Aminooxy TMTs outperform the hydrazide reagents in terms of labeling efficiency
      (>95% vs 65% at 0.1 MUM) and mass spectrometry based quantification using
      heavy/light-TMT labeled glycans enabled accurate quantification in MS1 spectra
      (CV < 15%) over a broad dynamic range (up to 1:40). In contrast, isobaric TMT
      labeling with quantification of reporter ions in tandem mass spectra suffered
      from severe ratio compression already at low sample ratios. To demonstrate the
      practical utility of the developed approach, we characterized the global N-linked
      glycosylation profiles of the isogenic human colon carcinoma cell lines SW480
      (primary tumor) and SW620 (metastatic tumor). The data revealed significant down
      regulation of high-mannose glycans in the metastatic cell line.

PMID- 22455666
TI  - Occupational skin diseases.
AB  - Occupational skin diseases are the most commonly reported notifiable occupational
      diseases. In Germany, 23 596 out of a total of 71 263 reported occupational
      diseases in 2010 were classified as occupational skin diseases (BK No. 5101:
      "severe or recurrent skin diseases which have forced the person to discontinue
      all occupational activities that caused or could cause the development,
      worsening, or recurrence of the disease"). Contact dermatitis (allergic,
      irritant) of the hands is the most common skin disease and atopic skin diathesis
      is often an important co-factor. The number of work-related skin diseases is many
      times higher than the number of notified occupational dermatoses. This CME
      article explains the legal framework of occupational diseases, the tasks and
      obligations of the legal statutory work insurance. Typical allergens and
      irritants of high risk professions are also presented as are the important steps
      from diagnosis to compensation. Early prevention of occupational skin diseases is
      very important to avoid severe chronic hand eczema. Therefore the
      "dermatologist's report" is crucial. Other occupational dermatoses (outside of BK
      5101) are briefly mentioned. In recent years the number of notifications of
      occupational skin cancer due to occupational UV-irradiation has increased.
      According to recent epidemiological findings, there is a significant and
      consistent positive association between occupational UV-irradiation and squamous
      cell carcinoma. Therefore, an important criterion for a new occupational disease
      is fulfilled.

PMID- 22455667
TI  - Palladium-catalyzed cycloaddition of alkynyl aryl ethers with internal alkynes
      via selective ortho C-H activation.
AB  - Alkynyl aryl ethers react with internal alkynes through selective ortho C-H
      activation by a palladium(0) catalyst to give substituted 2-methylidene-2H
      chromenes. The alkynoxy group acts as a directing group to promote ortho C-H
      functionalization. Deuterium-labeling experiments indicated that the
      arylpalladium hydride complex is a key intermediate via oxidative addition.
      Various functional groups tolerate the present transformation to give the
      corresponding products.

PMID- 22455668
TI  - Differential growth response and carbohydrate metabolism of global collection of
      perennial ryegrass accessions to submergence and recovery following de
      submergence.
AB  - Submergence can severely affect the growth of perennial grasses. The variations
      in growth and the physiological responses of perennial grass germplasm to
      submergence stress are not well understood. The objective of this study was to
      characterize the responses of diverse perennial ryegrass accessions to
      submergence and their recovery following de-submergence. One hundred globally
      collected perennial ryegrass accessions were submerged for 7d followed by 7d of
      recovery in two experiments (Exp 1 and Exp 2), respectively. Compared to the
      pattern of the controls, the overall distribution in leaf color, chlorophyll
      fluorescence, plant height (HT), and growth rate (GR) shifted toward a high
      frequency of lower values under submergence in both experiments. The accessions
      were generally grouped into three types: fast growth with maintenance of color
      (escape, T1), slow growth with maintenance of color (quiescence, T2), and slow
      growth with loss of color (susceptible, ST). Under submergence, T1 had higher HT
      and GR than the other two groups except for GR of T2 in Exp 2 and had higher
      water-soluble carbohydrate (WSC) and fructan concentrations, as well as fructan
      to WSC ratio, than ST in Exp 1. Recovery of HT and GR were generally close to
      that of the control level except for HT of ST in Exp 2, but the carbohydrates
      fully recovered in all types of plants after 7d of de-submergence. Differential
      responses of perennial ryegrass accessions to submergence are useful in creating
      more tolerant materials and in further characterizing physiological and molecular
      mechanisms of submergence tolerance.

PMID- 22455669
TI  - Palladium-catalyzed direct C-H bond alkynylations of heteroarenes using gem
      dichloroalkenes.
AB  - Palladium-catalyzed direct alkynylations of heteroarenes were accomplished with
      inexpensive gem-dichloroalkenes as user-friendly electrophiles, which set the
      stage for a modular, step-economical synthesis of diversely decorated heteroaryl
      alkynes with ample scope.

PMID- 22455670
TI  - Personal exposure to PM(2.5) and urinary hydroxy-PAH levels in bus drivers
      exposed to traffic exhaust, in Trujillo, Peru.
AB  - Public transport vehicle drivers, especially in highly polluted or trafficked
      areas, are exposed to high levels of air pollutants. In this study, we assessed
      the influence of traffic on levels of hydroxy polycyclic aromatic hydrocarbons
      (OH-PAHs) in commercial bus drivers in Trujillo, Peru, by measuring the within
      shift changes in the urinary whole weight and creatinine-corrected concentrations
      of the PAH metabolites. We measured personal PM(2.5) as a proxy of exposure to
      traffic emission. Urine samples were collected daily from two bus drivers and
      three minivan drivers in Trujillo, pre-, mid-, post-work shift and on days when
      the drivers were off work (total n = 144). Ten OH-PAH metabolites were measured
      in the urine samples. Drivers were also monitored for exposure to PM(2.5) (n =
      41). Daily work shift (mean = 13.1 +/- 1.3 hr) integrated PM(2.5) was measured in
      the breathing zones of the drivers for an average of 10.5 days per driver. The
      differences across shift in OH-PAH concentrations were not statistically
      significant except for urinary 2-hydroxyfluorene (2-FLU) (p = 0.04) and 4
      hydroxyphenanthrene (4-PHE) (p = 0.01) and creatinine-corrected 4
      hydroxyphenanthrene (p = 0.01). Correlation between pairs of hydroxy-PAHs (rho =
      0.50 to 0.93) were highest for mid-shift samples. Concentrations of PM(2.5)
      (geometric mean = 64 MUg/m(3); 95% confidence limits = 52 MUg/m(3), 78 MUg/m(3))
      is similar to those measured in many other studies of traffic exposure. There was
      significant change across work shift for concentrations of only two of the OH
      PAHs (2-FLU and 4-PHE). Results indicate that the drivers may have had limited
      time for clearance of PAH exposure from the body between work shifts. Comparisons
      of the concentrations of creatinine-corrected hydroxy-PAH to those reported in
      other studies indicate that exposure of public transport drivers to PAH could be
      similar. By following the subjects over multiple days, this study gives an
      indication of appropriate exposure situations for the use of hydroxy-PAHs and
      will be beneficial in designing future occupational studies of PAH exposure.

PMID- 22455672
TI  - Ring-opening polymerization in carnosine under pressure.
AB  - Our high pressure Raman scattering experiments on carnosine, a dipeptide of L
      histidine and beta-alanine, show pressure induced ring-opening polymerization
      involving the imidazole ring. While the onset of polymeric transformation is
      found to be at ~2.8 GPa, a substantial fraction of the monomeric solid becomes
      polymerized by 12 GPa. On release to ambient conditions, the observed Raman
      spectra do not contain any of the Raman modes of the ambient phase.

PMID- 22455671
TI  - Use of the internet by Italian pediatricians: habits, impact on clinical practice
      and expectations.
AB  - BACKGROUND: Medical professionals go online for literature searches and
      communication with families.We administered a questionnaire to members of the
      Italian Society of Pediatrics to assess determinants of their use of the
      Internet, of social platforms and of personal health records during clinical
      practice. METHODS: All the 9180 members of the Italian Society of Pediatrics were
      invited to fill in a questionnaire concerning use of the Internet and usefulness
      of Internet-based tools during clinical practice. The questionnaire was
      administered through the SurveyMonkey(r) web platform. Logistic regression
      analysis was used to study factors affecting use and influence of the Internet in
      clinical practice. RESULTS: A total of 1335 (14.5%) members returned the
      questionnaire. Mean age was 49.2 years, 58.6% were female. 32.3% had access to
      the Internet through a Smartphone. 71.9% of respondents used the Internet during
      clinical practice, mainly searching for guidelines and drug references. Use of
      the Internet during clinical practice was more frequent among younger
      pediatricians (OR 0.964; 95% CI 0.591-0.978), males (OR 1.602; 95% CI 1.209
      2.123) and those living in Northern and Central Italy (OR 1.441; 95% CI 1.111
      1.869), while it was lower among family pediatricians. 94.6% of respondents were
      influenced in their clinical practice by information found on the Internet, in
      particular younger pediatricians (OR 0.96, 95% CI 0.932-0.989), hospital
      pediatricians (OR 2.929, 95% CI 1.708-5.024), and other pediatric profiles (OR
      6.143, 95%CI 1.848-20.423). 15.9% of respondents stated that social networks may
      be useful in pediatric practice. Slightly more than half (50.5%) of respondents
      stated that personal health records may be clinically relevant. Registrars and
      hospital pediatricians were more likely to perceive personal health records as
      useful tools for clinical practice. Additional resources pediatricians would like
      to access were free bibliographic databases and tools for interacting with
      families. CONCLUSIONS: Italian pediatricians frequently use the Internet during
      their practice. One-third of them access the Internet through a Smartphone.
      Interaction with families and their empowerment can be improved by the use of
      Internet tools, including personal health records, toward which respondents show
      a significant interest. Though, they show a general resistance to the
      introduction of social networks in clinical practice.

PMID- 22455674
TI  - Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science. A
      decade in biosecurity. Introduction.

PMID- 22455675
TI  - Public health surveillance and infectious disease detection.
AB  - Emerging infectious diseases, such as HIV/AIDS, SARS, and pandemic influenza, and
      the anthrax attacks of 2001, have demonstrated that we remain vulnerable to
      health threats caused by infectious diseases. The importance of strengthening
      global public health surveillance to provide early warning has been the primary
      recommendation of expert groups for at least the past 2 decades. However, despite
      improvements in the past decade, public health surveillance capabilities remain
      limited and fragmented, with uneven global coverage. Recent initiatives provide
      hope of addressing this issue, and new technological and conceptual advances
      could, for the first time, place capability for global surveillance within reach.
      Such advances include the revised International Health Regulations (IHR 2005) and
      the use of new data sources and methods to improve global coverage, sensitivity,
      and timeliness, which show promise for providing capabilities to extend and
      complement the existing infrastructure. One example is syndromic surveillance,
      using nontraditional and often automated data sources. Over the past 20 years,
      other initiatives, including ProMED-mail, GPHIN, and HealthMap, have demonstrated
      new mechanisms for acquiring surveillance data. In 2009 the U.S. Agency for
      International Development (USAID) began the Emerging Pandemic Threats (EPT)
      program, which includes the PREDICT project, to build global capacity for
      surveillance of novel infections that have pandemic potential (originating in
      wildlife and at the animal-human interface) and to develop a framework for risk
      assessment. Improved understanding of factors driving infectious disease
      emergence and new technological capabilities in modeling, diagnostics and
      pathogen identification, and communications, such as using the increasing global
      coverage of cellphones for public health surveillance, can further enhance global
      surveillance.

PMID- 22455676
TI  - Preventing biological weapon development through the governance of life science
      research.
AB  - The dual-use dilemma in the life sciences-that illicit applications draw on the
      same science and technology base as legitimate applications-makes it inherently
      difficult to control one without inhibiting the other. Since before the September
      11 attacks, the science and security communities in the United States have
      struggled to develop governance processes that can simultaneously minimize the
      risk of misuse of the life sciences, promote their beneficial applications, and
      protect the public trust. What has become clear over that time is that while
      procedural steps can be specified for assessing and managing dual-use risks in
      the review of research proposals, oversight of ongoing research, and
      communication of research results, the actions or decisions to be taken at each
      of these steps to mitigate dual-use risk defy codification. Yet the stakes are
      too high to do nothing, or to be seen as doing nothing. The U.S. government
      should therefore adopt an oversight framework largely along the lines recommended
      by the National Science Advisory Board for Biosecurity almost 5 years ago-one
      that builds on existing processes, can gain buy-in from the scientific community,
      and can be implemented at modest cost (both direct and opportunity), while
      providing assurance that a considered and independent examination of dual-use
      risks is being applied. Without extraordinary visibility into the actions of
      those who would misuse biology, it may be impossible to know how well such an
      oversight system will actually succeed at mitigating misuse. But maintaining the
      public trust will require a system to be established in which reasonably
      foreseeable dual-use consequences of life science research are anticipated,
      evaluated, and addressed.

PMID- 22455677
TI  - The evolution of law in biopreparedness.
AB  - The decade following the terrorist attacks on September 11, 2001, and ensuing
      anthrax exposures that same fall has seen significant legal reforms designed to
      improve biopreparedness nationally. Over the past 10 years, a transformative
      series of legal changes have effectively (1) rebuilt components of federal,
      state, and local governments to improve response efforts; (2) created an entire
      new legal classification known as "public health emergencies"; and (3) overhauled
      existing legal norms defining the roles and responsibilities of public and
      private actors in emergency response efforts. The back story as to how law plays
      an essential role in facilitating biopreparedness, however, is pocked with
      controversies and conflicts between law- and policymakers, public health
      officials, emergency managers, civil libertarians, scholars, and others.
      Significant legal challenges for the next decade remain. Issues related to
      interjurisdictional coordination; duplicative legal declarations of emergency,
      disaster, and public health emergency; real-time legal decision making; and
      liability protections for emergency responders and entities remain unresolved.
      This article explores the evolving tale underlying the rise and prominence of law
      as a pivotal tool in national biopreparedness and response efforts in the
      interests of preventing excess morbidity and mortality during public health
      emergencies.

PMID- 22455678
TI  - A decade of countering bioterrorism: incremental progress, fundamental failings.
AB  - The fear and disruption caused by the 2001 anthrax attacks understandably led
      Americans to seek enhanced biodefenses. However, the path followed since those
      attacks has left the country inadequately prepared to face further risks from
      biological attacks. Why has security against these threats been only partially
      achieved? This article suggests that our responses over the past decade can be
      sorted into 4 levels in order of increasing difficulty. First, we rapidly
      appropriated funds, augmented personnel, and mandated reorganization of agencies.
      Though not easy to accomplish, these steps were easily conceptualized and,
      whatever their imperfections, could rather assuredly be achieved. A second level
      was more demanding, but also quite achievable. It involved the amplification of
      ongoing efforts. These efforts sometimes suffered as they scaled up, but, though
      they were qualified by delays and uncertainties, we can point to real
      achievements at this level. A third level was more difficult: It required
      evolving new strategies to deal with this largely unprecedented problem. In this
      regard, we have so far had only glimmers of possibility. At a fourth level, our
      performance and our prospects are worse still. At this level, our problems stem
      from resistances inherent in our country's cultural and political framework. This
      article identifies some of these problems and suggests, regrettably, that they
      are not likely to be resolved until change is catalyzed by further, and more
      dramatically traumatic, attacks or natural disasters. If this situational
      assessment is correct, what remedial strategies should we pursue? The article
      distinguishes 3 strategic approaches: an evolutionary one in which the U.S.
      continues advancing along its present path; a radical approach that attempts to
      address the fourth-level issues; and a third approach that prepares for
      punctuated evolution. This third approach accepts the improbability of level 4
      change either by gradual evolution or by radical argument, but asserts that it is
      possible to lay the conceptual groundwork now for the radical changes that will
      be possible, even demanded, after a catastrophic incident. This approach,
      neglected at present, would be a valuable addition to our present efforts.

PMID- 22455679
TI  - Assessing a decade of public health preparedness: progress on the precipice?
AB  - September 11 and the subsequent anthrax attacks marked the beginning of
      significant investment by the federal government to develop a national public
      health emergency response capability. Recognizing the importance of the public
      health sector's contribution to the burgeoning homeland security enterprise, this
      investment was intended to convey a "dual benefit" by strengthening the overall
      public health infrastructure while building preparedness capabilities. In many
      instances, federal funds were used successfully for preparedness activities. For
      example, electronic health information networks, a Strategic National Stockpile,
      and increased interagency cooperation have all contributed to creating a more
      robust and prepared enterprise. Additionally, the knowledge of rarely seen or
      forgotten pathogens has been regenerated through newly established public health
      learning consortia, which, too, have strengthened relationships between the
      practice and academic communities. Balancing traditional public health roles with
      new preparedness responsibilities heightened public health's visibility, but it
      also presented significant complexities, including expanded lines of reporting
      and unremitting inflows of new guidance documents. Currently, a rapidly
      diminishing public health infrastructure at the state and local levels as a
      result of federal budget cuts and a poor economy serve as significant barriers to
      sustaining these nascent federal public health preparedness efforts. Sustaining
      these improvements will require enhanced coordination, collaboration, and
      planning across the homeland security enterprise; an infusion of innovation and
      leadership; and sustained transformative investment for governmental public
      health.

PMID- 22455680
TI  - U.S. medical countermeasure development since 2001: a long way yet to go.
AB  - The U.S. government has taken significant steps toward developing and acquiring
      vaccines, drugs, and other medical countermeasures (MCMs) to protect and treat
      the population after a biological attack. In contrast to 2001, there is now a
      procedure for the Department of Health and Human Services (HHS) to develop,
      license, and stockpile MCMs for civilian use. Another major accomplishment is
      smallpox preparedness: There is now an adequate supply of vaccine for every
      person in the U.S., and there is an alternative vaccine meant for
      immunocompromised people and those with close contact with them. In spite of
      these and other accomplishments, the U.S. government MCM effort has been
      criticized by federal advisory committees, National Academy of Sciences reports,
      a congressional commission, and outside analysts who state that the efforts lack
      central leadership and accountability and that the pace of progress has been
      slow. A clear operational strategy for using MCMs, which would guide their
      development and acquisition, is also lacking. In this article, we review key
      areas of progress made since 2001 to develop and acquire MCMs, and we summarize
      what we judge to be the most critical and often mentioned areas where
      improvements are needed.

PMID- 22455681
TI  - The people's role in U.S. national health security: past, present, and future.
AB  - Over the past decade, assumptions have been made and unmade about what officials
      can expect of average people confronting a bioterrorist attack or other major
      health incident. The reframing of the public in national discourse and doctrine
      from a panic-stricken mob to a band of hearty survivors is a positive development
      and more realistic in terms of the empirical record. So, too, is the realization
      that citizen contributions to national health security encompass not only
      individual preparedness and volunteerism but also mutual aid and collective
      deliberation of the tough choices posed by health disasters. In projecting what
      needs to occur over the next 10 years in biosecurity, 2 priority challenges
      emerge: retaining the lesson that a public prone to panic, social disorder, and
      civil unrest is a myth, and building an infrastructure to bolster the public's
      full contributions to health emergency management.

PMID- 22455682
TI  - Collaboration in state health departments on the immunization program during the
      H1N1 response.

PMID- 22455683
TI  - [To create with meticulous care so as to reach a new hight].

PMID- 22455684
TI  - [New understanding of genetics of polycystic ovary syndrome].

PMID- 22455685
TI  - [Effect of follicle stimulating hormone on the secretion of anti-mullerian
      hormone in the granulosa cells in patients with polycystic ovarian syndrome].
AB  - OBJECTIVE: To study the effect of follicle stimulating hormone (FSH) on the
      secretion of anti-mullerian hormone (AMH) in granulosa cells in patients with
      polycystic ovarian syndrome (PCOS). METHODS: From Aug. 2008 to Dec. 2009, 33
      patients with PCOS in Reproductive Medicine Research Center, Sixth Affiliated
      Hospital of Sun Yat-sen University were collected from 8-10 mm antral follicles
      and classified into the following three groups: FSH-unstimulated granulosa cells
      (unstimulated group, n = 12), exogenous FSH-stimulated granulosa cells (exo
      stimulated group, n = 12) and internal FSH-stimulated granulosa cells (int
      stimulated group, n = 21). ELISA and real-time PCR were relatively used to
      measure protein and mRNA level of AMH. Luciferase reporting vector was
      constructed to detect the promoter activity of AMH. RESULTS: The levels of AMH
      secretion in PCOS granulosa cells were (11.4 +/- 4.0) ug/L in unstimulated group,
      (7.9 +/- 1.1) ug/L in exo-stimulated group and (5.6 +/- 1.7) ug/L in int
      stimulated group. Both the external and internal stimulation of FSH may suppress
      AMH secretion significantly (P < 0.05). The mRNA level of AMH in PCOS granulosa
      cells were 2.5 +/- 1.2 in unstimulated group, which were higher than 1.5 +/- 0.5
      in exo-stimulated group and 1.1 +/- 0.7 in int-stimulated group significantly (P
      < 0.05). The luciferase activity of AMH in PCOS granulosa cells were 11.5 +/- 2.3
      in unstimulated group, 8.7 +/- 2.4 in exo-stimulated group and 6.8 +/- 2.4 in int
      stimulated group. The luciferase activity of AMH in unstimulated group was
      significantly higher than those in exo-stimulated and int-stimulated groups (P <
      0.05). CONCLUSION: FSH may inhibit the excessive secretion of AMH and stimulate
      follicle growth in PCOS granulosa cells by suppressing activity and expression of
      promoter.

PMID- 22455686
TI  - [Correlation between interleukin-1 and the obesity of polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate the correlation between interleukin-1beta (IL-1beta),
      interleukin-1 receptor antagonist (IL-1ra) and the obesity of polycystic ovary
      syndrome (PCOS). METHODS: (1) From Oct. 2006 to Jan. 2007, 118 PCOS patients were
      enrolled in this study in Peking University Third Hospital, which were divided
      into 56 patients in obese PCOS group and 62 patients in non-obese PCOS group
      according to the WHO International Obesity Task Force Asia-Pacific criteria [body
      mass index (BMI) 25 kg/m(2)]. The polymorphism of IL-1beta gene promoter region,
      exon-5 and intron 2 of IL-1ra gene were detected by PCR. (2) Twenty-nine obese
      PCOS patients and 31 non-obese PCOS patients were selected randomizedly serum
      levels of IL-1beta, IL-1ra were measured by ELISA, in the mean time, serum levels
      of fasting glucose, fasting insulin and the total white blood cell,
      hypersensitive C-reactive protein levels were measured. RESULTS: (1) Genetic
      test:the frequency of TT genotype and T allele of IL-1beta promoter region (-511)
      in obese PCOS patients were significantly higher than those in non-obese patients
      (44.6% vs. 11.3%, 63.4% vs. 39.5%, all P < 0.05). The frequency of IL-1raI/V
      genotype and V allele of IL-1ra gene were 19.6% and 9.8% in obese PCOS patients,
      which were significantly higher than those in non-obese group (3.2% and 1.6%, P <
      0.05). (2) Serological test:serum level of IL-1beta and IL-1ra of (149 +/- 36)
      and (284 +/- 97) ng/L in obese PCOS group which were significantly higher than
      those in non-obese PCOS group [(96 +/- 42) and (208 +/- 84) ng/L, P < 0.05].
      Fasting blood glucose, fasting insulin and hypersensitive C-reactive protein and
      white blood cell count were (5.1 +/- 0.7) mmol/L, (17 +/- 9) mU/L, (1.5 +/- 0.6)
      mg/L and (7.0 +/- 2.3) * 10(9)/L in obese PCOS group, which were significantly
      higher than in non-obese PCOS group [(4.9 +/- 0.5) mmol/L, (11 +/- 8) mU/L, (0.9
      +/- 0.4) mg/L and (5.9 +/- 1.3) * 10(9)/L, P < 0.05]. (3)The correlation between
      interleukin and BMI: serum levels of IL-1beta (r = 0.673) and IL-1ra (r = 0.557)
      were positively correlated with BMI in PCOS patients (P < 0.05). CONCLUSIONS:
      Inflammatory factors IL-1beta and IL-1ra had correlation with obesity of PCOS
      patients, PCOS patients who carried T allele of IL-1beta gene promoter region (
      511) and V allele of IL-1ra gene were high risk of obesity.

PMID- 22455687
TI  - [Clinical application of in vitro maturation of human immature oocytes for
      infertile women with polycystic ovary syndrome].
AB  - OBJECTIVE: To investigate clinical effect and safety of in vitro maturation (IVM)
      of human immature oocytes in infertile women with polycystic ovary syndrome by
      comparing with conventional in vitro fertilization(IVF)and intracytoplasmic sperm
      injection(ICSI). METHODS: From Jan. 2003 to Dec. 2009, 157 infertile women with
      PCOS underwent 162 cycles IVM in Center for Reproductive Medicine, the First
      Affiliated Hospital of Anhui Medical University. In the mean time, 109 patients
      with PCOS underwent 114 IVF/ICSI cycles as control group 1 and 106 patients with
      other factors underwent 106 IVF/ICSI cycles as control group 2. Treatment and
      outcome of pregnancy and infant were compared among those 3 groups. RESULTS: No
      statistically significant difference were found in terms of the positive rate of
      hCG in urine [35.7% (56/157), 42.2% (46/109), 44.3% (47/106)], the rate of
      clinical pregnancy [29.3% (46/157), 37.6% (41/109), 41.5% (44/106)], the rate of
      entopic pregnancy [1.9% (3/157), 1.8% (2/109), 0.9% (1/106)], the rate of
      miscarriage [18.6% (8/43), 12.8% (5/39), 20.9% (9/43)] and the rate of live-birth
      [22.3% (35/157), 31.2% (34/109), 32.1% (34/106)] among three groups (IVM group,
      control group 1, control group 2, P > 0.05). The rate of preterm labor, low
      weight newborn, mean birth weight, ratio of male to female did not show
      significantly difference among 3 groups (P > 0.05). The average control ovarian
      stimulation was 6 days, the median dose of gonadotropin (Gn) was 675 IU, and the
      total hospital cost was (8392 +/- 1328) RMB in IVM group, which were
      statistically lower than those in the other two control groups (P < 0.01). The
      rate of multiple pregnancy was 4.7% (2/43) and ovarian hyperstimulation syndrome
      (OHSS) 0 in IVM group, which were significantly lower than those in the other
      control group (P < 0.01). CONCLUSION: In vitro maturation is an effective
      treatment in infertile women with PCOS, it could obtain the similar pregnancy
      outcome and reduce total cost, the dosage of gonadotropin-releasing hormone and
      rate of OHSS compared with conventional IVF/ICSI.

PMID- 22455688
TI  - [Activation and significance of the PI3K/Akt pathway in endometrium with
      polycystic ovary syndrome patients].
AB  - OBJECTIVE: To investigate activation of the phosphatidylinositol 3-kinase
      (PI3K)/protein kinase B (Akt) pathway in the endometrium of women with polycystic
      ovary syndrome (PCOS) and its role in endometrium hyperplasia and carcinogenesis,
      and the factors affecting the activation of the PI3K/Akt pathway. METHODS: From
      Jan 2007 to Jun 2008, 52 patients with PCOS who underwent dilatation and
      curettage were selected as experimental group matched with 32 non-PCOS patients
      as control group. Serous hormonal parameters, fasting blood glucose and insulin,
      body mass index (BMI), and endometrium pathology were measured and evaluated in
      all patients. The PCOS patients were divided into insulin resistance and non
      insulin resistance group according to homeostasis model assessment-insulin
      resistance index (HOMA-IR). Meanwhile, the PCOS patients were grouped as normal,
      endometrial hyperplasia and carcinoma depending on outcome of pathology. The
      expression of Akt and phosphorylated Akt (p-Akt) were determined by western blot.
      RESULTS: (1) The expression of p-Akt was significantly higher in PCOS group [(46
      +/- 18)%] than that in control [(33 +/- 9)%, P < 0.01)]. (2) The expression of p
      Akt was significantly higher in group of endometrial hyperplasia and carcinoma
      [(56 +/- 19)%] when compared with those in normal endometria group [(31 +/- 12)%,
      P < 0.05]; the expression of p-Akt was significantly higher in group of insulin
      resistance [(50 +/- 19)%] compared with that in non-insulin resistance group [(34
      +/- 10)%, P < 0.01]. (3) There was a positive correlation between the expression
      level of p-Akt in endometrium with PCOS and HOMA-IR and BMI respectively (r =
      0.400, 0.326, both P < 0.05). CONCLUSIONS: The PI3K/Akt pathway was over
      activated in endometrium with PCOS which may be associated with the formation of
      endometrial hyperplasia and carcinoma in PCOS patients. Insulin resistance and
      obesity may be high risk factors for over-activation of the PI3K/Akt pathway in
      endometrium with PCOS.

PMID- 22455689
TI  - [Association between osteoprotegerin gene polymorphisms and severe pre-eclampsia
      in Chinese women].
AB  - OBJECTIVE: To investigate the potential association between 163A/G and 950T/C
      polymorphisms of osteoprotegerin (OPG) gene and severe pre-eclampsia. METHODS:
      Eighty-five severe pre-eclamptic patients and 81 normal term pregnant women (as
      control group) were recruited from the Department of Obstetrics and Gynecology,
      West China Second University Hospital, Sichuan University during the period from
      July 2007 to March 2009, and they were all Han population living in Chengdu,
      China. Genotype and allele frequencies of 163A/G and 950T/C were determined by
      the PCR-restriction fragment length polymorphism (RFLP) assay. Clinical and
      biochemical parameters for different alleles between the patients and controls
      were compared for statistical significance respectively, such as blood pressure,
      serum creatinine and 24-hour urine protein. RESULTS: The observed and expected
      genotype counts were consistent with Hardy-Weinberg equilibrium. No significant
      differences were found in the genotype and allele frequencies of 163A/G and
      950T/C polymorphisms between the two groups (P > 0.05). However, in the
      preeclamptic group, serum creatinine was significantly higher in women with the
      AG + GG genotypes [(76 +/- 24) umol/L] compared with AA genotype [(56 +/- 18)
      umol/L]. Reversely, birth weight was lower in the AG + GG genotypes [(2040 +/-
      721) g] than those in the AA genotype [(2520 +/- 810) g], and the P < 0.05,
      respectively. In the severe pre-eclampsia, 950T/C TT genotype carriers exhibited
      significantly higher systolic blood pressure [(153 +/- 16) mm Hg (1 mm Hg = 0.133
      kPa)] and 24-hour urine protein [(4.0 +/- 2.5) g] compared with TT + TC carriers
      [(145 +/- 17) mm Hg, (2.9 +/- 1.8) g], respectively, furthermore the P < 0.05.
      CONCLUSIONS: In severe pre-eclampsia, carriers with G allele at position 163A/G
      has more genetic predisposition than A allele carriers, as well as 950T/C T
      allele carriers compared with C carriers. Taken together, this study suggested
      that OPG gene polymorphisms might be associated with some clinical parameters of
      severe pre-eclampsia.

PMID- 22455690
TI  - [Expression of various subtypes of human leukocyte antigen-G in placenta of
      patients complicated with severe pre-eclampsia].
AB  - OBJECTIVE: To investigate the different expression of various subtypes of human
      leukocyte antigen-G (HLA-G) in placenta of patients complicated with severe pre
      eclampsia. METHODS: Ten placental samples from early-onset severe pre-eclamptic
      pregnancies and ten from late-onset severe pre-eclamptic pregnancies were
      collected as study group; ten placental samples from preterm pregnancies and ten
      from normal pregnancies were collected as control group. The levels of HLA-G
      protein in the four groups were measured by western blot and
      immunohistochemistry. RESULTS: (1) HLA-G1 protein decreased significantly in both
      the early-onset (2.4 +/- 0.6 versus 2.9 +/- 1.1, P < 0.05) and the late-onset pre
      eclampsia groups (3.5 +/- 2.1 versus 4.2 +/- 2.4, P < 0.05). (2) HLA-G5 protein
      increased in the late-onset pre-eclampsia groups (1.8 +/- 1.1 versus 1.1 +/- 0.9,
      P < 0.05); the increase in the early-onset pre-eclampsia group is not obvious
      (1.6 +/- 0.9 versus 1.4 +/- 0.7, P > 0.05). (3) The level of HLA-G1 protein in
      placenta from patients complicated with premature labor is lower (2.9 +/- 1.1
      versus 4.2 +/- 2.4, P < 0.05); HLA-G5 protein does not change significantly (1.4
      +/- 0.7 versus 1.1 +/- 0.9, P > 0.05). (4) HLA-G1 and G5 proteins mainly express
      in the placenta extravillous cytotrophoblast cells. There is also a high level of
      expression around the blood vessels and in the extraembryonic mesoderm.
      CONCLUSIONS: (1) HLA-G1 decreased significantly in both the early-onset and late
      onset pre-eclamptic patients. (2) HLA-G5 increased in both the early-onset and
      late-onset pre-eclamptic patients, and the increase in the late-onset pre
      eclamptic patients is obvious. (3) In late pregnancy, the level of HLA-G1 is
      lower in patients complicated with premature labor, this may be the result of its
      earlier pregnancy week; HLA-G5 does not change significantly. (4) HLA-G1 and G5
      mainly express in the placenta extravillous cytotrophoblast cells.

PMID- 22455691
TI  - [Significance of prognostic evaluation of International Federation of Gynecology
      and Obstetrics 2009 staging system on stage I endometrioid adenocarcinoma].
AB  - OBJECTIVE: To explore the impact of 2009 International Federation of Gynecology
      and Obstetrics (FIGO) staging system alteration for stage I endometrioid
      adenocarcinoma on its' prognosis assessing. METHODS: A retrospective study was
      carried out on 244 cases with endometrial carcinoma admitted in Peking University
      People's Hospital from Jan.1995 to Feb.2008. RESULTS: (1) All 244 patients were
      divided into FIGO 2009 Ia group (n = 200) and FIGO 2009 Ib group (n = 44)
      according to FIGO 2009 staging system, while they were divided into FIGO 1988 Ia
      group (n = 34), FIGO 1988 Ib group (n = 156) and FIGO 1988 Ic group (n = 29). The
      others 25 cases were stage IIa (n = 16) and stage IIIa with merely positive
      abdominal cytology (n = 9) according to FIGO 1988 staging system.(2) The higher
      percentage of low-grade in FIGO 1988 Ia group than that in FIGO 2009 Ia group (P
      = 0.003). Compared with FIGO 2009 Ia group, the age of the patients, surgery
      extent, the percentage of lymph node excision and received chemotherapy and
      radiotherapy, there were no difference in FIGO 1988 Ia and Ib group, respectively
      (P > 0.05). There were 5.9% (2/34) and 6.7% (10/150) found relapse among FIGO
      1988 Ia group and FIGO 1988 Ib group, and there were 2.9% (1/34) and 2.7% (4/150)
      for the two groups died of carcinoma. Compared with FIGO 2009 Ia group, there
      were not significant difference [7.5% (13/200) vs. 3.0% (6/200); P > 0.05]. The 5
      years and 10 years progression-free survival (PFS) of FIGO 1988 Ia group and Ib
      group were (97.0 +/- 3.0)%, (90.9 +/- 6.5)% and (95.3 +/- 2.1)%, (90.2 +/- 3.6)%,
      respectively, in which there were not significant difference compared with that
      in FIGO 2009 Ia group [(96.1 +/- 1.6)%, (89.6 +/- 3.2)%; P > 0.05]. The 5 years
      and 10 years overall survival (OS) in FIGO 1988 Ia group and Ib group were 100%,
      (93.8 +/- 6.0)% and (96.9 +/- 1.8)%, (95.2 +/- 2.5)%, respectively, in which
      there were did not significant difference with that in FIGO 2009 Ia group [(97.9
      +/- 1.2)%, (93.4 +/- 2.8)%; P > 0.05].(3) There were not significant difference
      between FIGO 1988 Ic group and FIGO 2009 Ib group (P > 0.05) for the age of the
      patients, grade, surgery extent, lymph node excision, the percentage of received
      chemotherapy and radiotherapy. Between FIGO 1988 Ic group and FIGO 2009 Ib group,
      there were 3.4% (1/29) and 6.8% (3/44) cases found relapse, respectively. And
      there were 0 and 2.3% (1/44) cases died of carcinoma in the two groups, in which
      there were not differ much either (P > 0.05). The 5 years and 10 years PFS in
      FIGO 1988 Ic group were all 100%, while they were 100% and (90.9 +/- 6.2)% in
      FIGO 2009 Ib group. The 5 years and 10 years OS in FIGO 1988 Ic group were all
      100%, but were 100% and (95.0 +/- 4.9)% in FIGO 2009 Ib group, in which they all
      did not significantly differ much (P > 0.05). (4) The patients in FIGO 2009 Ia
      group were younger than those in FIGO 2009 Ib group (P < 0.01). The percentage of
      low grade in FIGO 2009 Ia group were higher than that in FIGO 2009 Ib group (P =
      0.029). The percentages of received chemotherapy and radiotherapy in FIGO 2009 Ia
      group were lower than that in FIGO 2009 Ib group remarkably (P < 0.01). But there
      were not significant difference in the uterine excision extent and the percentage
      of lymph node excision between the two groups (P > 0.05). There were not
      significantly differ in the relapse rates and the death rates between the FIGO
      2009 Ia group and FIGO 2009 Ib group (P > 0.05). There were also not significant
      difference in PFS and OS between the two groups (P > 0.05). CONCLUSIONS: There
      were not significant difference in the prognosis between FIGO 2009 stage Ia and
      FIGO 1988 stage Ia and Ib. There were also not significant difference in the
      prognosis between FIGO 2009 stage Ia and FIGO 2009 stage Ib, which may be due to
      received more chemotherapy and radiotherapy in FIGO 2009 stage Ib patients.

PMID- 22455694
TI  - How external performance standards inform self-assessment.

PMID- 22455692
TI  - [Clinical analysis of 15 cases of malignant ovarian germ cell tumors with lung
      metastasis].
AB  - OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and
      prognosis of malignant ovarian germ cell tumors (MOGCT) with lung metastasis.
      METHODS: Fifteen patients of MOGCT with lung metastasis treated in Peking Union
      Medical College Hospital from Jan. 1982 to Dec. 2010 was retrospectively
      analyzed. RESULTS: (1) Clinical characteristics: the average onset age of these
      15 patients is (23 +/- 11) years old (6 - 48 years). The majority of these
      patients presented with abdominal pain (8/15) or irregular vaginal bleeding
      (4/15) as their initial symptoms. The primary tumor located in the left ovary in
      8 cases, right ovary in 6 cases, and both sides in only 1 case. Metastatic
      lesions were confined to the lung in 12 patients, while the other 3 patients were
      found to have multi-site distant metastasis. (2) DIAGNOSIS:all 15 cases included
      9 pure non-gestational ovarian choriocarcinoma (NGOC), 3 MOGCT containing
      choriocarcinoma component (one mature teratoma with choriocarcinoma component,
      one endodermal sinus tumor with embryonal carcinoma and choriocarcinoma
      components, one choriocarcinoma with dysgerminoma component), 2 embryonal
      carcinoma, one immature teratoma. Only one patient in these 15 cases was
      correctly diagnosed before surgery. (3) Time of lung metastasis:of 12 MOGCT with
      choriocarcinoma component, 11 patients were found to have lung metastasis in the
      course of their primary treatment, only 1 had lung metastasis 2 months after the
      synthetic treatment finished. Three MOGCT patients without choriocarcinoma
      component were all found to have lung metastasis when tumor relapsed in the
      advanced stages of the disease. (4) TREATMENT:all 15 patients received multi
      agent chemotherapy combined with surgery. The mean courses of chemotherapy for
      these patients were 16 courses (5 - 43 courses). (5) PROGNOSIS: of these 15
      cases, complete remission was obtained in 10 patients of NGOC or mixed ovarian
      germ cell tumors with choriocarcinoma component, 3 patients (one NGOC, one
      endodermal carcinoma and one immature teratoma, respectively) died in the course
      of treatment as result of tumor progression, 2 progressed cases (one NGOC and one
      endodermal carcinoma respectively) abandoning therapy were lost to follow up.
      CONCLUSIONS: MOGCT with lung metastasis are more often to found in NGOC patients.
      These patients could obtain high complete remission rate after standard multi
      agent chemotherapy combined with surgery. The prognosis of MOGCT with lung
      metastasis containing choriocarcinoma component are better than that of those
      without containing choriocarcinoma component.

PMID- 22455695
TI  - Twelve tips for using the objective structured teaching exercise for faculty
      development.
AB  - BACKGROUND: The importance of faculty development to improve clinicians' teaching
      skills has been well articulated in the literature. There are few objective
      measures of the impact of faculty development on teaching skills. The objective
      structured teaching exercise (OSTE) is a faculty development tool that may meet
      this challenge. It also has great potential to be used in the development and
      enhancement of teaching skills. The OSTE consists of a simulated teaching
      scenario involving a standardized learner with objective and immediate feedback
      given to the teacher, and includes a pre-determined behaviourally based scale or
      checklist to assess teaching performance. AIM: There is little information in the
      literature on the practical aspects of how to develop and deliver an OSTE in a
      faculty development context. Based on our experience, we created a framework to
      guide the use of the OSTE for faculty development. METHODS: Twelve tips for using
      the OSTE for faculty development are outlined in this article. These include:
      clarifying the goal and target audience, identifying what teaching skills to
      focus on, developing the scenario and the assessment tool, choosing and training
      the standardized learner, holding a dry run, protecting the teacher, integrating
      the OSTE into one's own context and promoting buy-in, and evaluating the
      activity. CONCLUSIONS: The OSTE is a novel tool to enhance faculty development.
      We describe 12 key elements that are important for its successful development and
      delivery.

PMID- 22455696
TI  - Improving the accuracy of self-assessment of practical clinical skills using
      video feedback--the importance of including benchmarks.
AB  - INTRODUCTION: Isolated video recording has not been demonstrated to improve self
      assessment accuracy. This study examines if the inclusion of a defined standard
      benchmark performance in association with video feedback of a student's own
      performance improves the accuracy of student self-assessment of clinical skills.
      METHODS: Final year medical students were video recorded performing a
      standardised suturing task in a simulated environment. After the exercise, the
      students self-assessed their performance using global rating scales (GRSs). An
      identical self-assessment process was repeated following video review of their
      performance. Students were then shown a video-recorded 'benchmark performance',
      which was specifically developed for the study. This demonstrated the competency
      levels required to score full marks (30 points). A further self-assessment task
      was then completed. Students' scores were correlated against expert assessor
      scores. RESULTS: A total of 31 final year medical students participated. Student
      self-assessment scores before video feedback demonstrated moderate positive
      correlation with expert assessor scores (r = 0.48, p < 0.01) with no change after
      video feedback (r = 0.49, p < 0.01). After video feedback with benchmark
      performance demonstration, self-assessment scores demonstrated a very strong
      positive correlation with expert scores (r = 0.83, p < 0.0001). CONCLUSIONS: The
      demonstration of a video-recorded benchmark performance in combination with video
      feedback may significantly improve the accuracy of students' self-assessments.

PMID- 22455697
TI  - Assessment of an innovative instructional program to return non-practicing
      physicians to the workforce.
AB  - INTRODUCTION: Few formal educational programs are available in the United States
      to assist physicians wishing to return to medical practice after clinical
      inactivity. Little published data on physicians who complete these programs
      exist. We describe the Drexel Medicine Physician Reentry/Refresher course and
      present our findings on participant demographics, performance, and goal
      attainment following course completion. METHODS: Physician self-assessment,
      future career goals, recommendations of referring organizations, and a
      quantitative assessment of knowledge and skills were used to create
      individualized learning objectives and physician's curriculum. Initial assessment
      included demonstration of clinical skills using standardized patients and medical
      knowledge using the National Board of Medical Examiners Comprehensive Clinical
      Medicine Self-Assessment Examination. Progress in knowledge and clinical skills
      was measured by repeat assessment at course completion. We questioned physicians
      3 months after course completion to determine if initial goals were attained.
      RESULTS: Thirty-six physicians completed the program from November 2006 through
      November 2010. Most physicians demonstrated significant improvement in core
      clinical skills and knowledge at the end of the course. All physicians who sought
      employment, hospital privileges, and refreshing skills as initial goals were
      successful. CONCLUSION: The Drexel Medicine Physician Reentry/Refresher course
      provides a unique model for successfully returning inactive physicians to
      clinical practice.

PMID- 22455698
TI  - The multiple mini-interview in the U.K. context: 3 years of experience at Dundee.
AB  - BACKGROUND: The multiple mini-interview (MMI) is a new interview process that
      Dundee Medical School has recently adopted to assess entrants into its
      undergraduate medicine course. This involves an 'objective structured clinical
      examination' like rotational approach in which candidates are assessed on
      specific attributes at a number of stations. AIMS:  To present methodological,
      questionnaire and psychometric data on the transitional process from traditional
      interviews to MMIs over a 3-year period and discuss the implications for those
      considering making this transition. METHODS:  To facilitate the transition, a
      four-station MMI was piloted in 2007. Success encouraged consideration of
      desirable attributes which were used to develop a full 10-station process which
      was implemented in 2009 with assessors being recruited from staff, students and
      simulated patients. A questionnaire was administered to all assessors and
      candidates who participated in the 2009 MMIs. Cronbach's alpha and Pearson's r
      and analysis of variances were used to determine the MMI's psychometric
      properties. Multi-faceted Rasch modelling (MFRM) was modelled to control for
      assessor leniency/stringency and the impact of using 'fair scores' determined.
      Analysis was conducted using SPSS 17 and FACETS 3.65.0. RESULTS:  The
      questionnaire confirmed that the process was acceptable to all parties.
      Cronbach's alpha reliability was satisfactory and consistent. Graduates/mature
      candidates outperformed U.K. school-leavers and overseas candidates. Using MFRM
      fair scores would change the selection outcome of 6.2% and 9.6% of candidates in
      2009 and 2010, respectively. Students were less lenient, made more use of the
      full range of the rating scales and were just as reliable as staff. CONCLUSIONS: 
      The strategy of generating institutional support through staged introduction
      proved effective. The MMI in Dundee was shown to be feasible and displayed sound
      psychometric properties. Student assessors appeared to perform at least as well
      as staff. Despite a considerable intellectual and logistical challenge MMIs were
      successfully introduced and deemed worthwhile.

PMID- 22455699
TI  - Characterizing changes in student empathy throughout medical school.
AB  - BACKGROUND:  Empathy is important in the physician-patient relationship. Prior
      studies suggest that medical student empathy declines with clinical training.
      AIMS:  We examined the trend of empathy longitudinally; determined differences in
      empathy according to gender and medical specialty preferences; and determined
      empathy and career preference differences among students admitted through
      different medical school admission pathways. METHOD:  The data for this study
      were collected using a longitudinal cohort design and included 2652 observations
      nested within 1162 individuals. Participants were medical students at a
      university-based medical school surveyed yearly from 2007 through 2010. Empathy
      was measured by the Jefferson Scale of Physician Empathy-Student Version (JSPE
      S), a validated, 20-item self-administered questionnaire. Predictors of JSPE-S
      scores included gender, age, anticipated financial debt upon graduation and
      future career interest. RESULTS:  Empathy scores of students in preclinical years
      were higher than in clinical years. Gender was a significant predictor of
      empathy, with women having higher empathy scores than men. Students preferring
      technology-oriented specialties had lower empathy scores. When career preference
      was controlled, higher levels of debt were significantly associated with greater
      empathy. Students with high baseline empathy decreased less than students with
      low baseline empathy during medical school. Students in traditional four-year
      medical school programs had higher baseline empathy than those in early pathway
      programs. CONCLUSIONS:  Self-reported empathy for patients, a possibly critical
      factor in high-quality patient-centered care, wanes as students advance in
      clinical training, particularly among those entering technology-oriented
      specialties. In the era of new health care policy and primary care shortages, our
      research may have implications for the medical education system and admission
      policy.

PMID- 22455700
TI  - What do we do? Practices and learning strategies of medical education leaders.
AB  - BACKGROUND: Continuous changes in undergraduate and postgraduate medical
      education require faculty to assume a variety of new leadership roles. While
      numerous faculty development programmes have been developed, there is little
      evidence about the specific practices of medical education leaders or their
      learning strategies to help inform their design. AIM: This study aimed to explore
      what medical education leaders' actually do, their learning strategies and
      recommendations for faculty development. METHOD: A total of 16 medical education
      leaders from a variety of contexts within the faculty of medicine of a large
      North American medical school participated in semi-structured interviews to
      explore the nature of their work and the learning strategies they employ. Using
      thematic analysis, interview transcripts were coded inductively and then
      clustered into emergent themes. RESULTS: Findings clustered into four key themes
      of practice: (1) intrapersonal (e.g., self-awareness), (2) interpersonal (e.g.,
      fostering informal networks), (3) organizational (e.g., creating a shared vision)
      and (4) systemic (e.g. strategic navigation). Learning strategies employed
      included learning from experience and example, reflective practice, strategic
      mentoring or advanced training. CONCLUSIONS: Our findings illuminate a four
      domain framework for understanding medical education leader practices and their
      learning preferences. While some of these findings are not unknown in the general
      leadership literature, our understanding of their application in medical
      education is unique. These practices and preferences have a potential utility for
      conceptualizing a coherent and relevant approach to the design of faculty
      development strategies for medical education leadership.

PMID- 22455701
TI  - Evaluating clinical teachers with the Maastricht clinical teaching questionnaire:
      how much 'teacher' is in student ratings?
AB  - BACKGROUND: Students are a popular source of data to evaluate the performance of
      clinical teachers. Instruments to obtain student evaluations must have proven
      validity. One aspect of validity that often remains underexposed is the
      possibility of effects of between-student differences and teacher and student
      characteristics not directly related to teaching performance. AIM: The authors
      examined the occurrence of such effects, using multilevel analysis to analyse
      data from the Maastricht clinical teaching questionnaire (MCTQ), a validated
      evaluation instrument, in a veterinary curriculum. METHODS: The 15-item MCTQ
      covers five domains. The authors used multilevel analysis to divide the variance
      in the domain scores in components related to, respectively, teachers and
      students. They estimated subsequent models to explore how the MCTQ scores are
      dependent on teacher and student characteristics. RESULTS: Significant amounts of
      variance in student ratings were due to between-teacher differences, particularly
      for learning climate, modelling and coaching. The effects of teacher and student
      characteristics were mostly non-significant or small. CONCLUSION: Large portions
      of variance in MCTQ scores were due to differences between teachers, while the
      contribution of student and teacher characteristics was negligible. The results
      support the validity of student ratings obtained with the MCTQ for evaluating
      teacher performance.

PMID- 22455702
TI  - Teaching about medically unexplained symptoms at medical schools in the United
      Kingdom.
AB  - BACKGROUND: Medically unexplained symptoms (MUS) are very common in primary and
      secondary care. They are often inappropriately managed, resulting in potential
      harm to patients as well as wasted resources. To bring about change, it is
      important that newly qualified doctors are equipped with the skills to manage MUS
      effectively. We do not know if and how this topic is currently taught at U.K.
      medical schools. AIM: To document whether, how and when this topic is currently
      taught in U.K. medical schools. To assess potential barriers to this teaching and
      consider how it can be improved. METHODS: A questionnaire survey emailed to GP
      and psychiatry teaching leads at all 31 U.K. medical schools. RESULTS: Responses
      received from 24/31 schools showed that MUS teaching across U.K. medical schools
      is very variable in terms of amount, method, assessment and integration of the
      teaching within the curriculum. Most respondents identified a need for a greater
      quantity of cross-discipline teaching and for greater value to be attributed to
      the topic. CONCLUSION: Inconsistent and disparate teaching across medical schools
      may lead to very variable practice amongst qualified clinicians. In order to
      overcome this, consensus is needed as to how and where in the undergraduate
      curriculum there should be teaching about MUS.

PMID- 22455703
TI  - Enhancing situational interest in pediatrics.
AB  - BACKGROUND: Individual interest, something that persists regardless of the
      situation, and situational interest, finding personal value in an educational
      context, have not been studied in medical student education. OBJECTIVE: To
      determine if individualized case discussions enhance interest in pediatric
      medicine. METHODS: During the 2008/2009 academic year, 88 clerkship students
      participated in clinical case discussions. At orientation, students completed an
      Interest in Pediatrics (IIP) questionnaire, responding 1 = strongly disagree to 5
      = strongly agree. Intervention and control groups were randomly assigned. The
      intervention group personalized cases to students' medical specialty interests.
      The control group discussed the case presentation. Groups met twice during the 8
      week clerkships, completing a post-IIP at the end of the clerkship. RESULTS:
      Intervention group interest increased from pre-IIP, mean = 3.64, to post-IIP,
      mean = 4.22 (z = -2.994, p < 0.05, r = -0.44). On post-IIP, application of
      pediatric medicine increased for both groups; the intervention group was most
      significant from pre-IIP, mean = 1.09, to post-IIP, mean = 4.33 (z = -6.038, p <
      0.05, r = -0.88). DISCUSSION: Enhanced interest in pediatrics from the
      intervention group indicates that creating a learning environment personally
      relevant to students' careers facilitates interest to learn.

PMID- 22455704
TI  - Study guides improves self-learning skills in clinical endocrinology.

PMID- 22455705
TI  - Medical students in theatre: setting the scene.

PMID- 22455706
TI  - The evaluation of feasibility and expectations of study abroad among Chinese
      medical students.

PMID- 22455707
TI  - Improvement of medical students' clinical performances after remediation program.

PMID- 22455708
TI  - From patient to instructor: honoring the lived experience.

PMID- 22455709
TI  - Experiences with an honors paper as part of the psychiatry clerkship.

PMID- 22455712
TI  - The role of blended learning in the clinical education of healthcare students: a
      systematic review.
AB  - BACKGROUND: Developing practice knowledge in healthcare is a complex process that
      is difficult to teach. Clinical education exposes students to authentic learning
      situations, but students also need epistemological access to tacit knowledge and
      clinical reasoning skills in order to interpret clinical problems. Blended
      learning offers opportunities for the complexity of learning by integrating face
      to-face and online interaction. However, little is known about its use in
      clinical education. AIM: To determine the impact of blended learning in the
      clinical education of healthcare students. METHODS: Articles published between
      2000 and 2010 were retrieved from online and print sources, and included multiple
      search methodologies. Search terms were derived following a preliminary review of
      relevant literature. RESULTS: A total of 71 articles were retrieved and 57 were
      removed after two rounds of analysis. Further methodological appraisals excluded
      another seven, leaving seven for the review. All studies reviewed evaluated the
      use of a blended learning intervention in a clinical context, although each
      intervention was different. Three studies included a control group, and two were
      qualitative in nature. Blended learning was shown to help bridge the gap between
      theory and practice and to improve a range of selected clinical competencies
      among students. CONCLUSION: Few high-quality studies were found to evaluate the
      role of blended learning in clinical education, and those that were found provide
      only rudimentary evidence that integrating technology-enhanced teaching with
      traditional approaches have potential to improve clinical competencies among
      health students. Further well-designed research into the use of blended learning
      in clinical education is therefore needed before we rush to adopt it.

PMID- 22455713
TI  - Virtual patients for assessment of medical student ability to integrate clinical
      and laboratory data to develop differential diagnoses: comparison of results of
      exams with/without time constraints.
AB  - INTRODUCTION: We have evaluated medical student ability in a problem-based
      learning course using a virtual patient (VP)-based exam with variable parameters
      for assessment purposes. METHODS: A class of 155 second year medical students was
      assessed using a VP exam with unlimited access during a 1-week period; 2 years
      later, the identical exam was administered to 175 students with a 3-h time limit.
      RESULTS: Students taking the exam without time constraints utilized approximately
      twice as much time than students with the time limit. Without the pressure of a
      time-limit, students utilized half as many inquiries of the patient history,
      physical, and lab/imaging tests than were used by students having a time
      constraint, indicating that the time limited students used a "shotgun approach"
      to try to collect as many "required" inquiries as possible. Most students (91%)
      taking the untimed exam were able to correctly diagnose the exam case but only
      31% of the time limited students correctly diagnosed the VP exam case, despite
      their higher number of inquiries. CONCLUSIONS: Our results demonstrate that an
      identical VP exam, administered with variables to compare untimed versus time
      limited conditions, resulted in an unraveling of student's ability to integrate
      the data discovered during the process of progressive disclosure.

PMID- 22455714
TI  - Hidden benefits of a peer-mentored 'Hospital Orientation Day': first-year medical
      students' perspectives.
AB  - BACKGROUND: Entering the clinical environment is potentially stressful for junior
      medical students. AIMS: We evaluated first-year medical student feedback on a
      peer-mentored 'Hospital Orientation Day' designed to provide insight into future
      clinical training. METHOD: Using a mixed methodology approach data were collected
      from first-year medical students. Responses to a questionnaire were used to
      develop a topic guide for focus groups held the next academic year. The
      questionnaire was completed by 230 first-year students and 32 second years
      participated in the interviews. Thematic analysis was used to draw conclusions.
      RESULTS: Analysis of questionnaire responses indicated that students gained
      insight into future learning. Focus groups then generated five themes: (1)
      entering the hospital without fear, (2) linking the present with the future, (3)
      understanding the culture of learning in the clinical years, (4) a 'Backstage
      Pass' to the clinical world and (5) peer mentors make or break the day.
      CONCLUSIONS: Using peer mentors during the Hospital Orientation Day allowed
      insight into future learning. We highlight the importance of student Mentors in
      the success of hospital orientation. To maximise the benefits for first years, we
      recommend a mentor selection procedure, mentor training opportunities and
      incentives to optimise mentor performance.

PMID- 22455715
TI  - The relationship between medical students' learning approaches and performance on
      a summative high-stakes clinical performance examination.
AB  - BACKGROUND: A learning approach embeds the intention of the student when starting
      a task and the learning processes and strategies used to carry out a task.
      Student approaches to learning have been categorized as deep, strategic, and
      surface. AIM: To explore the relationships among medical students' learning
      approaches, gender, and performance on a summative high-stakes clinical
      performance examination (CPX). METHODS: We measured medical students' learning
      approaches at the beginning of year four using the Approaches and Study Skills
      Inventory for Students and compared results with CPX scores. RESULTS: Student
      scores in the top two quartiles of the CPX were significantly higher on the deep
      approach than student CPX scores in the bottom quartile, and student scores in
      the bottom quartile of the CPX were significantly higher on the surface approach
      than scores for the other three CPX quartiles. CPX patient-physician interaction
      scores showed a significant positive correlation with deep approach scores, and
      CPX overall patient satisfaction scores showed a significant positive correlation
      with deep and strategic approach scores. Surface approach scores correlated
      negatively with all CPX score categories. CONCLUSION: Approach to learning was
      associated with performance on a high-stakes CPX.

PMID- 22455716
TI  - Using an objective structured video exam to identify differential understanding
      of aspects of communication skills.
AB  - BACKGROUND: Effective communication in health care is associated with patient
      satisfaction and improved clinical outcomes. Professional schools increasingly
      incorporate communication training into their curricula. The objective structured
      video exam (OSVE) is a video-based examination that provides an economical way of
      assessing students' knowledge of communication skills. This study presents a
      scoring strategy that enables blueprinting of an OSVE to consensus guidelines, to
      determine which aspects of communication skills create the most difficulty for
      students to understand and to what degree understanding improves through
      experiential communication skills training. METHODS: Five interactions between a
      healthcare professional and client were scripted and filmed using standardized
      patients. The dialogues were mapped onto the Kalamazoo consensus statement by
      having five communication experts view each video and identify effective and
      ineffective use of communication skills. Undergraduate students enrolled in a
      communications course completed an OSVE on three occasions. RESULTS: A total of
      79 students completed at least one testing session. The scores assigned supported
      the validity of the scoring strategy as an indication of knowledge growth.
      Considerable variability was observed across Kalamazoo sub-domains. CONCLUSION:
      With further refining, this scoring approach may prove useful for educators to
      tailor their education and assessment practices to specific consensus guidelines.

PMID- 22455717
TI  - Clinical audit in the final year of undergraduate medical education: towards
      better care of future generations.
AB  - BACKGROUND: In Australia, in an environment undergoing rapidly changing
      requirements for health services, there is an urgent need for future
      practitioners to be knowledgeable, skilful and self-motivated in ensuring the
      quality and safety of their practice. Postgraduate medical education and
      vocational programs have responded by incorporating training in quality
      improvement into continuing professional development requirements, but
      undergraduate medical education has been slower to respond. AIMS: This article
      describes the clinical audit programme undertaken by all students in the final
      year of the medical course at the University of Notre Dame, Fremantle, Australia,
      and examines the educational worth of this approach. METHODS: Data were obtained
      from curricular documents, including the clinical audit handbook, and from
      evaluation questionnaires administered to students and supervisors. RESULTS: The
      clinical audit programme is based on sound educational principles, including
      situated and participatory learning and reflective practice. It has demonstrated
      multi-dimensional benefits for students in terms of learning the complexities of
      conducting an effective audit in professional practice, and for health services
      in terms of facilitating quality improvement. CONCLUSION: Although this programme
      was developed in a medical course, the concept is readily transferable to a
      variety of other health professional curricula in which students undertake
      clinical placements.

PMID- 22455718
TI  - The development of the CoRE-Values framework as an aid to ethical decision
      making.
AB  - BACKGROUND: Ethical analysis frameworks can help to identify the ethical
      dimensions to clinical care and provide a method for justifying clinical
      decisions. Published frameworks, however, have some limitations to easy,
      practical use. AIMS: The aim was to identify a comprehensive yet easy-to-use
      framework that clarifies ethical decision-making, suitable for use by medical
      learners and clinical educators. METHOD: A literature search identified published
      frameworks that define the components of ethical clinical decision-making. On
      this basis, a new framework, the 'CoRE-Values Compass and Grid' was constructed.
      This was formally evaluated during a medical school interprofessional teaching
      session. RESULTS: For 88% of 228 medical and nursing students, the new framework
      was easy to understand; 85% reported it as easy to use. The framework improved
      awareness of the ethical dimensions to a clinical scenario for 97% of students
      and the ability to systematically identify ethical aspects for 83%. Students and
      instructors reported that the framework helped to link ethics theory with
      clinical practice. The framework was described as a useful educational tool by
      85% of students and 95% of instructors. CONCLUSIONS: The 'CoRE-Values Compass and
      Grid' is a new framework, shown to aid the systematic identification and
      consideration of ethical aspects to clinical cases.

PMID- 22455719
TI  - The audience response system and knowledge gain: a prospective study.
AB  - INTRODUCTION: The introduction of an audience response system (ARS) in the
      obstetrics and gynaecology course for medical students at The University of
      Western Australia provided an opportunity to measure knowledge gain by ARS
      lecture formats compared with didactic lectures. METHODS: The study was conducted
      over four obstetrics and gynaecology terms, alternating the ARS and didactic
      format between two selected lectures each term. Students completed multiple
      choice quizzes immediately post-lectures and 5 weeks later. RESULTS: Immediate
      post-lecture quiz mean scores for the ARS lectures were significantly higher
      compared with scores for the didactic lectures (7.5 vs. 6.7, p < 0.001). Pairwise
      comparisons between ARS and didactic lectures for each lecture topic showed
      significantly higher quiz scores for ARS lectures (preterm labour 8.3 vs. 7.4, p
      = 0.032; and prenatal diagnosis 6.9 vs. 6.0, p = 0.014). Quiz scores for the
      didactic preterm labour lecture were significantly higher than scores for the
      didactic prenatal diagnosis lecture (6.0 vs. 7.4, p < 0.001). Quiz results at 5
      weeks showed no differences in scores between the ARS and the didactic lectures
      and no differences between lecture topics. CONCLUSIONS: Use of the ARS in
      lectures appeared to improve knowledge gain immediately post-lecture but no
      difference was found after retesting at 5 weeks.

PMID- 22455720
TI  - Adverse events from spinal manipulation in the pregnant and postpartum periods: a
      critical review of the literature.
AB  - BACKGROUND: The safety of spinal manipulation during pregnancy and the postpartum
      periods has been a matter of debate among manual therapists. Spinal manipulative
      therapy during these periods is a commonly performed intervention as
      musculoskeletal pain is common in these patients. To date there has not been an
      evaluation of the literature on this topic exclusively. METHODS: A literature
      search was conducted on PubMed, CINAHL and the Index to Chiropractic Literature
      along with reference searching for articles published in English and French in
      the peer-reviewed literature that documented adverse effects of spinal
      manipulation during either pregnancy or postpartum. Case reports, case series,
      and any other clinical study designs were deemed acceptable for inclusion, as
      were systematic reviews. The appropriate Scottish Intercollegiate Guidelines
      Network (SIGN) tools were used to rate included articles for quality when
      applicable. RESULTS: Five articles identifying adverse events in seven subjects
      following spinal manipulation were included in this review, along with two
      systematic reviews. The articles were published between 1978 and 2009. Two
      articles describing adverse effects from spinal manipulation on two postpartum
      patients were included, while the remaining three articles on five patients with
      adverse effects following spinal manipulation were on pregnant patients. Injury
      severity ranged from minor injury such as increasing pain after treatment that
      resolved within a few days to more severe injuries including fracture, stroke,
      and epidural hematoma. SIGN scores of the prospective observational cohort study
      and systematic reviews indicated acceptable quality. CONCLUSIONS: There are only
      a few reported cases of adverse events following spinal manipulation during
      pregnancy and the postpartum period identified in the literature. While improved
      reporting of such events is required in the future, it may be that such injuries
      are relatively rare.

PMID- 22455721
TI  - Helminth parasite proteomics: from experimental models to human infections.
AB  - Schistosomiasis is a major human helminth infection endemic in developing
      countries. Urogenital schistosomiasis, caused by S. haematobium, is the most
      prevalent human schistosome disease in sub-Saharan Africa. Currently control of
      schistosome infection is by treatment of infected people with the anthelmintic
      drug praziquantel, but there are calls for continued efforts to develop a vaccine
      against the parasites. In order for successful vaccine development, it is
      necessary to understand the biology and molecular characteristics of the
      parasite. Ultimately, there is need to understand the nature and dynamics of the
      relationship between the parasite and the natural host. Thus, my studies have
      focused on molecular characterization of different parasite stages and
      integrating this information with quantitative approaches to investigate the
      nature and development of protective immunity against schistosomes in humans.
      Proteomics has proved a powerful tool in these studies allowing the proteins
      expressed by the parasite to be characterized at a molecular and immunological
      level. In this review, the application of proteomic approaches to understanding
      the human-schistosome relationship as well as testing specific hypotheses on the
      nature and development of schistosome-specific immune responses is discussed. The
      contribution of these approaches to informing schistosome vaccine development is
      highlighted.

PMID- 22455723
TI  - Detection and molecular characterization of avian Plasmodium from mosquitoes in
      central Turkey.
AB  - Assessing vector-parasite relationship is important in understanding the
      emergence of vector-borne diseases and the evolution of parasite diversity. This
      study investigates avian Plasmodium parasites in mosquitoes collected from
      Kayseri province in Central Anatolian, Turkey and determines the haemosporidian
      parasite lineages from these mosquito species. A total of 6153 female mosquitos
      from 6 species were collected from 46 sites during June-August of 2008 and 2009.
      Each mosquito's head-thorax and abdomen were separated, categorized with respect
      to species and collection area and pooled for DNA extraction. A total of 1198
      genomic DNA pools (599 thorax-head, 599 abdomen) were constituted of which 128
      pools (59 thorax-head, 69 abdomen) were positive for avian haemosporidian
      parasites (Plasmodium and Haemoproteus) by Nested-PCR analysis. Culex pipens,
      Aedes vexans, Culex theileri and Culiseta annulata were positive with minimum
      infection rates (MIRs) of 16.22 and 18.15, 4.72 and 5.98, 5.18 and 10.36, 10.64
      and 10.64 in their thorax-head and abdomen parts, respectively. No avian
      haemosporidian DNA was detected from Culex hortensis and Anopheles maculipennis.
      Phylogenetic analyses of the partial cytb gene of avian haemosporidian mt-DNA
      from 13 positive pools revealed that 11 lineages in four phylogenic groups were
      Plasmodium and the other two were Haemoproteus. Our results suggest that Cx.
      pipiens could probably be the major vector of avian Plasmodium in Central Turkey.
      This is the first report of molecular detection and characterization of avian
      Plasmodium lineages from mosquitoes in Turkey.

PMID- 22455722
TI  - Determining fetal manganese exposure from mantle dentine of deciduous teeth.
AB  - Studies addressing health effects of manganese (Mn) excess or deficiency during
      prenatal development are hampered by a lack of biomarkers that can reconstruct
      fetal exposure. We propose a method using the neonatal line, a histological
      feature in deciduous teeth, to identify regions of mantle dentine formed at
      different prenatal periods. Micromeasurements of Mn in these regions may be used
      to reconstruct exposure at specific times in fetal development. To test our
      hypothesis, we recruited pregnant women before 20 weeks gestation from a cohort
      of farmworkers exposed to Mn-containing pesticides. We collected house floor dust
      samples and mother's blood during the second trimester; umbilical cord blood at
      birth; and shed deciduous incisors when the child was ~7 years of age. Mn levels
      in mantle dentine formed during the second trimester (as (55)Mn:(43)Ca area under
      curve) were significantly associated with floor dust Mn loading (r(spearman) =
      0.40; p = 0.0005; n = 72). Furthermore, (55)Mn:(43)Ca in sampling points
      immediately adjacent the neonatal line were significantly associated to Mn
      concentrations in cord blood (r(spearman) = 0.70; p = 0.003; n = 16). Our results
      support that Mn levels in mantle dentine are useful in discerning perinatal Mn
      exposure, offering a potentially important biomarker for the study of health
      effects due to environmental Mn exposure.

PMID- 22455724
TI  - In vitro activity of neem (Azadirachta indica) and cassava (Manihot esculenta) on
      three pre-parasitic stages of susceptible and resistant strains of Teladorsagia
      (Ostertagia) circumcincta.
AB  - Anthelmintic resistance of gastrointestinal nematodes is considered as one of the
      main limiting factors causing significant economic losses to the small ruminant
      industry. The anthelmintic properties of some plants are among the suggested
      alternative solutions to control these parasitic worms. The present study
      investigated the anthelmintic activity of neem (Azadirachta indica) and cassava
      (Manihot esculenta) leaf extracts against the susceptible and resistant strains
      of one of the most important nematodes in small ruminants, Teladorsagia
      (Ostertagia) circumcincta. Three different in vitro tests: egg hatch test, larval
      development assay, and larval paralysis assay were used to determine the
      efficiency of neem and cassava extracts on three pre-parasitic stages of T.
      circumcincta. The LC(50) was determined for the most potent extract in each plant
      as well as the phytochemical tests, total tannin quantification and cytotoxicity
      on peripheral blood mononuclear cells of goats. The results revealed a high
      anthelmintic activity of neem methanol extract (NME) and cassava methanol extract
      (CME) on both strains of T. circumcincta without significant differences between
      the strains. The first stage larvae were more sensitive with the lowest LC(50) at
      7.15 mg/ml and 10.72 mg/ml for NME and CME, respectively, compared with
      44.20mg/ml and 56.68 mg/ml on eggs and 24.91 mg/ml and 71.96 mg/ml on infective
      stage larvae.

PMID- 22455725
TI  - Antibody fusions reduce onset of experimental Cryptosporidium parvum infection in
      calves.
AB  - Cryptosporidium parvum is one of the main causes of diarrhea in neonatal calves
      resulting in significant morbidity and economic losses for producers worldwide.
      We have previously demonstrated efficacy of a new class of antimicrobial antibody
      fusions in a neonatal mouse model for C. parvum infection. Here, we extend
      efficacy testing of these products to experimental infection in calves, the
      principal target species. Neonatal calves were challenged with C. parvum oocysts
      and concomitantly treated with antibody-biocide fusion 4H9-G1-LL37 over the
      course of four days. This resulted in reduced severity of the disease when
      compared to control animals. Overall clinical health parameters showed
      significant improvement in treated animals. Oocyst shedding was reduced in
      treated when compared to control animals. Control of oocyst shedding is a
      prerequisite for breaking the cycle of re-infection on dairy farms. Antibody
      biocide fusion products thus have the potential to reduce the impact of the
      infection in both individual animals and in the herd.

PMID- 22455727
TI  - Alan Houghton.

PMID- 22455726
TI  - Protein arginine methyltransferase 6 regulates embryonic stem cell identity.
AB  - Histone arginine methylation has emerged as an important histone modification
      involved in gene regulation. Protein arginine methyltransferase (PRMT) 4 and 5
      have been shown to play essential roles in early embryonic development and in
      embryonic stem (ES) cells. Recently, it has been reported that PRMT6-mediated di
      methylation of histone H3 at arginine 2 (H3R2me2) can antagonize tri-methylation
      of histone H3 at lysine 4 (H3K4me3), which marks active genes. However, whether
      PRMT6 and PRMT6-mediated H3R2me2 play crucial roles in early embryonic
      development and ES cell identity remain unclear. Here, we have investigated their
      roles using gain and loss of function studies with mouse ES cells as a model
      system. We report that Prmt6 and histone H3R2 methylation levels increased when
      ES cells are induced to differentiate. Consistently, we find that differentiation
      of ES cells upon upregulation of Prmt6 is associated with decreased expression of
      pluripotency genes and increased expression of differentiation markers. We also
      observe that elevation of Prmt6 increases the methylation level of histone H3R2
      and decreases H3K4me, Chd1, and Wdr5 levels at the promoter regions of Oct4 and
      Nanog. Surprisingly, knockdown of Prmt6 also leads to downregulation of
      pluripotency genes and induction of expression of differentiation markers
      suggesting that Prmt6 is important for ES cell pluripotency and self-renewal. Our
      results indicate that a critical level of Prmt6 and histone H3R2me must be
      maintained in mouse ES cells to sustain their pluripotency.

PMID- 22455728
TI  - Effect of hydration on structural and thermodynamic properties of pig gastric and
      bovine submaxillary gland mucins.
AB  - One of the essential functions of mucous gel is protection of tissues against
      dehydration. The effect of hydration on the structural and thermodynamic
      properties of pig gastric mucin (PGM) and bovine submaxillary gland mucin (BSM)
      have been studied using atomic force microscopy (AFM), sorption, and differential
      scanning calorimetry (DSC). The analysis of sorption isotherms shows the higher
      water sorption capacity of PGM compared to BSM at RH levels lower than about 78%.
      The value of the hydration enthalpy at zero water content at 25  degrees C for
      both biopolymers is about -20 kJ/mol. Glass transitions of BSM and PGM occur at
      RH levels between 60 and 70% for both mucins. AFM indicates the presence of a
      dumbbell structure as well as a fiber-like structure in PGM samples. The
      experimental volume of the dry dumbbell molecule obtained by AFM is 3140 +/- 340
      nm(3). Using DSC data, the amount of nonfreezing water was calculated to be about
      0.51 g/g of PGM. The phase diagram of PGM demonstrates two regions of different
      Tg: dependent and independent of hydration levels. In particular, at mucin
      concentrations from 0 to 67 wt %, the glass transition occurs at a constant
      temperature of about -15  degrees C. At higher concentrations of mucin, Tg is
      increasing with increasing mucin concentrations. 

PMID- 22455729
TI  - Phylogenetic diversity of nitrogen-fixing bacteria and the nifH gene from
      mangrove rhizosphere soil.
AB  - Nine types of nitrogen-fixing bacterial strains were isolated from 3 rhizosphere
      soil samples taken from mangrove plants in the Dongzhaigang National Mangrove
      Nature Reserve of China. Most isolates belonged to Gammaproteobacteria
      Pseudomonas, showing that these environments constituted favorable niches for
      such abundant nitrogen-fixing bacteria. New members of the diazotrophs were also
      found. Using a soil DNA extraction and PCR-cloning-sequencing approach, 135
      clones were analyzed by restriction fragment length polymorphism (RFLP) analysis,
      and 27 unique nifH sequence phylotypes were identified, most of which were
      closely related to sequences from uncultured bacteria. The diversity of nitrogen
      fixing bacteria was assessed by constructing nifH phylogenetic trees from
      sequences of all isolates and clones in this work, together with related nifH
      sequences from other mangrove ecosystems in GenBank. The nifH diversity varied
      among soil samples, with distinct biogeochemical properties within a mangrove
      ecosystem. When comparing different mangrove ecosystems, the nifH gene sequences
      from a specific site tended to cluster as individual groups. The results provided
      interesting data and novel information on our understanding of diazotroph
      community diversity in the mangrove ecosystems.

PMID- 22455730
TI  - Advances in graphene-related technologies: synthesis, devices and outlook.
AB  - Graphene has been the subject of many scientific investigations since exfoliation
      methods facilitated isolation of the two-dimensional material. During this time,
      new synthesis methods have been developed which have opened technological
      opportunities previously hindered by synthetic constraints. An update on the
      recent advances in graphene-based technologies, including synthesis and
      applications into electrical, mechanical and thermal uses will be covered. A
      special focus on the patent space and commercial landscape will be given in an
      effort to identify current trends and future commercialization of graphene
      related technologies.

PMID- 22455731
TI  - Contact mechanics at nanometric scale using nanoindentation technique for brittle
      and ductile materials.
AB  - In the last years, Nanoindentation or Instrumented Indentation Technique has
      become a powerful tool to study the mechanical properties at micro/nanometric
      scale (commonly known as hardness, elastic modulus and the stress-strain curve).
      In this review, the different contact mechanisms (elastic and elasto-plastic) are
      discussed, the recent patents for each mechanism (elastic and elasto-plastic) are
      summarized in detail, and the basic equations employed to know the mechanical
      behaviour for brittle and ductile materials are described.

PMID- 22455732
TI  - Near infrared spectroscopy patents for the physicochemical characterization of
      nanomaterials: the road from production to routine high-throughput quality
      control.
AB  - The measurement of the physical and chemical ("physicochemical") properties of
      nanomaterials used in industry and science including chemistry, pharmacy,
      medicine, toxicology, etc., is time-consuming, expensive and requires a lot of
      experience of a well trained lab staff. Near-infrared spectroscopy (NIR; 4.000
      12.000 cm(-1)), working in the wavelength region with the highest IR energy,
      allows obtaining multifactorial information of the material under investigation
      due to the occurrence of a high number of combination and overtone vibrations.
      Coupling of an optimized and well-designed measurement technique with
      multivariate data analysis (MVA) leads to a non-destructive, fast, reliable and
      robust novel NIR technique for the fast and non-invasive physicochemical
      characterization, which is suitable for high-throughput quality control due to
      the short analyses times of only a few seconds. In the following chapters, the
      patented basic NIR techniques full-filling these aims are introduced, described,
      summarized and critically discussed.

PMID- 22455733
TI  - C60 fullerene derivatized nanoparticles and their application to therapeutics.
AB  - Fullerenes can be formed into many new materials and devices. They have a wide
      range of applications in medicine, electronics, biomaterials, and energy
      production. An overview of the nanostructure and the physical and chemical
      characteristics of fullerene-drug derivatives is given. The biological behavior
      of fullerene derivatives shows their potential to medical application fields
      because C(60) is rapidly absorbed by tissues and is excreted through urinary
      tract and enterons, which reveals low toxicity in vitro and in vivo studies.
      Nanomedicine has become one of the most promising areas of nanotechnology, while
      many have claimed its therapeutic use against cancer, human immunodeficiency
      virus (HIV), and neurodegenerative disorders. Water-soluble C(60) fullerene
      derivatives that come from chemical modification largely enhance the biological
      efficacy. The blood-brain barrier (BBB) is a physical barrier composed of
      endothelial tight junctions that restrict the paracellular permeability. A major
      challenge facing neuropharmacology is to find compounds that can be delivered
      into the brain through the bloodstream. Fullerene C(60) was demonstratively able
      to cross the BBB by hybridizing a biologically active moiety dyad, which provides
      a promising clue as a pharmacological therapy of neural disorders.

PMID- 22455734
TI  - Microporous polycarbazole with high specific surface area for gas storage and
      separation.
AB  - Microporous polycarbazole via straightforward carbazole-based oxidative coupling
      polymerization is reported. The synthesis route exhibits cost-effective
      advantages, which are essential for scale-up preparation. The Brunauer-Emmett
      Teller specific surface area for obtained polymer is up to 2220 m(2) g(-1). Gas
      (H(2) and CO(2)) adsorption isotherms show that its hydrogen storage can reach to
      2.80 wt % (1.0 bar and 77 K) and the uptake capacity for carbon dioxide is up to
      21.2 wt % (1.0 bar and 273 K), which show a promising potential for clean energy
      application and environmental field. Furthermore, the high selectivity toward
      CO(2) over N(2) and CH(4) makes the obtained polymer possess potential
      application in gas separation.

PMID- 22455736
TI  - [Prenatal diagnosis for thalassemias].

PMID- 22455735
TI  - Simvastatin ointment, a new treatment for skin inflammatory conditions.
AB  - BACKGROUND: Statins represent a class of drugs that effectively lowers
      cholesterol, however they also possess pleiotropic effects, like promotion of
      angiogenesis, prevention of bone loss, immunomodulatory and anti-inflammatory
      effects. OBJECTIVES: Thus, the aim of this study was to investigate the activity
      of simvastatin topically applied in mice in acute and chronic skin inflammation
      models. METHODS: Skin inflammation was induced in mice ears by topical
      application of 12-O-tetradecanoylphorbol acetate (TPA). In the acute model, ear
      oedema was measured by the increase of ear thickness 6h after TPA (2.5MUg/ear).
      The chronic inflammatory process was induced by multiple applications of TPA
      (2.0MUg/ear) for nine alternate days, and the oedema was measured daily as the
      increase in ear thickness. RESULTS: Topical treatment was applied immediately
      after TPA in acute model or started at 5th day of chronic experiment. For acute
      model treatment was simvastatin (0.24, 0.71 and 2.40MUM), dexamethasone
      (0.13MUM), both in acetone or vehicle alone (acetone). In chronic model
      simvastatin (1% and 3%) and dexamethasone (0.5%) were incorporated in ointment
      preparations, and a group received ointment alone (vehicle). Samples of ear
      tissue (6mm) were taken from acute and chronic models, weighted and prepared for
      histological analysis and myeloperoxidase (MPO) enzymatic activity evaluation.
      Application of simvastatin in acetone reduced the ear oedema after a single TPA
      application in a dose dependent manner [ID(50) of 0.47 (0.22-1.13) MUM], and the
      MPO enzymatic activity up to 61+/-10%. Also, both simvastatin ointment
      preparations 1% and 3% reduced acute TPA-induced ear oedema in 55+/-7% and 65+/
      8%, respectively. In the chronic model, simvastatin ointment 1% was able to
      reduce ear oedema (25+/-3%) and ear weight (10+/-1%), though 3% formulation
      augmented both parameters. Histological analysis revealed a reduction of swelling
      and leukocyte migration in the acute model for both the formulations of
      simvastatin (1% and 3%), while in chronic model simvastatin 1% decreased ear
      swelling and epidermal thickness, but simvastatin 3% increased both parameters.
      CONCLUSION: The results confirm the anti-inflammatory activity of simvastatin
      when applied topically in both acute and chronic models of skin inflammation.
      Besides, the formulation of simvastatin ointment 1% shows to be a very effective
      formulation for a chronic usage.

PMID- 22455737
TI  - [A study on gene mutation spectrums of alpha- and beta-thalassemias in
      populations of Yunnan Province and the prenatal gene diagnosis].
AB  - OBJECTIVE: To investigate mutation spectrums of alpha- and beta-haemoglobin genes
      in thalassemia patients and carriers in Yunnan province, and to establish
      procedures on prenatal gene diagnosis. METHODS: Totally 10 033 counseling couples
      and pregnant women, and 22 cases of children with moderate or severe thalassemia
      were recruited from 5 parts of Yunnan Province, middle, western, eastern,
      southern and northern areas, during July 2009 to July 2011. Medical records,
      including results of haemoglobin electrophoresis, blood routine examination, and
      gene diagnosis of subjects were collected and saved in an database in Excel
      software by the Key Laboratory for Birth Defects and Genetic Diseases. Using
      multiple gap-PCR and PCR-reversed dot blotting kits, DNA samples collected from
      1077 cases of haematological positive thalassemia patients and carriers were
      tested to determine common mutations of the alpha- or beta-haemoglobin genes. The
      codon regions of haemoglobin genes were sequenced by the Sanger sequencing in
      cases that the mutation tests were negative. Mutation spectrums of alpha- and
      beta-haemoglobin genes were concluded. Prenatal gene diagnosis was offered to
      fetuses who had risk of thalassemia major. RESULTS: (1) In 1077 cases of
      haemological screen positive subjects, deletions and mutations of alpha
      haemoglobin gene were tested in 119 subjects among 347 cases suspected as alpha
      thalassemia patients and carriers. Five kinds of deletions and mutations on alpha
      haemoglobin gene were found. In 104 subjects, four kinds of common deletions and
      mutations onalpha-haemoglobin gene were determined: --(SEA), -alpha(3.7),
      alpha(CS)alpha, -alpha(4.2). Other 14 subjects were double heterozygotes with
      haemoglobin H disease and severe alpha-thalassemia phenotypes. A rare mutation of
      insertion and deletion in alpha2 haemoglobin gene intron, alpha(301-24_301-23
      indel), was found in one carrier subject. (2) In 1077 cases of haemological
      screen positive subjects, deletions and mutations of beta-haemoglobin gene were
      tested in 297 subjects among 730 cases suspected as beta-thalassemia patients and
      carriers. Sixteen kinds of beta-haemoglobin gene mutations were found, including
      7 cases of rare abnormal haemoglobinopathy patients with beta-haemoglobin gene
      mutations. In one case with beta(+) phenotype patient, the Codon 5(-CT) mutation
      at beta-haemoglobin gene was found (firstly reported in China). (3) Three fetuses
      with high risks of alpha-thalassemia were accepted for prenatal diagnosis. One
      case of Hb Bart's hydrops syndrome fetus with the genotype --(SEA)/--(SEA), and
      one case of mild alpha-thalassemia fetus with the genotype
      alpha(CS)alpha/alphaalpha were found. Another one fetus was found with normal
      alpha-haemoglobin. In 6 fetuses accepted for prenatal diagnosis due to high risks
      of beta-thalassemia, one case of beta-thalassemia major with the genotype
      CD(17)(A->T)/-28(A->G) was found, 3 fetuses were heterozygote carriers, and 2
      fetuses had normal genotypes without mutations found in their parents. Medical
      terminations for 2 fetuses with severe thalassemia were made according to the
      choice of pregnant women. Other 7 pregnancies continued to term. Anemia or growth
      retardation was not found in the 7 infants when following up after given-birth 6
      to 12 months. CONCLUSIONS: The mutation spectrums of alpha- and beta-haemoglobin
      genes of thalassemia patients and carriers in Yunnan province are special, in
      which beta-haemoglobin gene exits more polymorphism in the mutation spectrum.
      Carrier screening in pregnant women, and offering prenatal gene diagnosis to the
      high risk pregnancies should be an efficient strategy to prevent thalassemia
      major.

PMID- 22455738
TI  - [Large-scale population-based genetic screening and prenatal diagnosis for
      thalassemias in Zhuhai City of Guangdong Province].
AB  - OBJECTIVE: To report the results of preventive control program of severe
      thalassemias in Zhuhai City of Guangdong Province from 1998 to 2010. METHODS: As
      the guide centre of marriage and childbearing and the greatest maternity hospital
      in Zhuhai City of Guangdong Province, Zhuhai Municipal Maternity and Child
      Healthcare Hospital constructed the genetic screening network for thalassemias
      testing and referred for follow-up and for genetic counseling. The couples for
      premarital medical examination or regular healthcare examination in pregnancy
      were enrolled to this preventive control program. A conventional strategy of
      screening for heterozygote was used to identify the alpha- and beta-thalassemia
      traits in women and their spouses according to the standard procedures of
      hematological phenotype analysis which was recommended by Thalassemia
      International Federation (TIF). Then those suspected couples at risk were
      diagnosed for alpha- and beta-thalassemia by PCR-based DNA assays. The couples at
      risk for severe thalassemias were counseled and offered prenatal diagnosis and
      termination of pregnancy in case of an affected fetus in the rights of consent
      and of option voluntarily. RESULTS: From January 1998 to December 2010, 85 522
      brides and grooms-to-be for premarital screening and 41 503 pregnant women in
      addition to 14 141 partners for prenatal screening were recorded, the covering
      rates of premarital screening and prenatal screening in the city were 92.698%
      (from 1998 to 2003) and 27.667% (from 2004 to 2010), respectively. Totally 10 726
      cases were found to be the carriers of thalassemias, with 7393 for alpha
      thalassemia (5.237%, 7 393/141 166) and 3333 for beta-thalassemia (2.361%, 3
      333/141 166). A total of 257 couples at-risk for severe thalassemias were
      detected including 190 for alpha-thalassemia and 67 for beta-thalassemia. Among
      them, 251 (97.7%, 251/257) couples were performed prenatal diagnosis. During the
      preventive control program, a total of 72 fetuses with severe thalassemias
      including hemoglobin H disease were voluntarily terminated. In Zhuhai City, the
      average annual birth rate of fetuses with severe thalassemia was declined by
      32.9% (49/149). CONCLUSIONS: This study has reduced effectively birth rate of
      perinatal infants with severe thalassemias in Zhuhai City by genetic screening
      and prenatal diagnosis of thalassemia in the large population of 13 years. Our
      summary comes out of technical proposals for prenatal screening and diagnosis,
      which could be take example by preventative control of thalassemia in other
      regions of China where are prevalent.

PMID- 22455739
TI  - [The value of MCV, MCH and HbA(2) in laboratory screening of thalassemia].
AB  - OBJECTIVES: To explore the roles of mean corpuscular volume (MCV), mean
      corpuscular hemoglobin (MCH) and hemoglobin A(2) (HbA(2)) in the laboratory
      screening of thalassemia, and to find optimal screening modality for different
      conditions. METHODS: From September 2008 to May 2011, 1384 subjects underwent
      thalassemia screening at Department of Obstetrics and Gynecology of Nanfang
      Hospital. Of them, 1036 cases were diagnosed with thalassemia (408 alpha
      thalassemia, 608 beta-thalassemia, and 20 alphabeta compound thalassemia,
      thalassemia group) and 348 without thalassemia, non-thalassemia group. All
      subjects were screened respectively for MCV, MCH and HbA(2). Analyses were
      performed in all subjects to assess the sensitivity, specificity, positive
      predictive value, negative predictive value and diagnostic accuracy respectively
      associated with MCV, MCH and HbA(2) alone, combination of MCV and MCH, and
      combination of MCV, MCH and HbA(2). RESULTS: (1) In the thalassemia group, the
      sensitivity of MCV alone was 92.9% (379/408) for alpha thalassemia, 99.3%
      (604/608) for beta thalassemia and 100.0% (20/20) for alphabeta compound
      thalassemia. In the non-thalassemia group, the specificity of MCV alone was 75.0%
      (261/348). (2) In the thalassemia group, the sensitivity of MCH alone was 92.9%
      (379/408) in alpha thalassemia, 99.0% (602/608) in beta thalassemia and 100.0%
      (20/20) in alphabeta compound thalassemia. In the non-thalassemia group, the
      specificity of MCH alone was 72.7% (253/348). (3) The sensitivity of Hb A(2)
      alone was 67.4% (275/408) for alpha thalassemia, 97.5% (593/608) for beta
      thalassemia, and 100% (20/20) for alphabeta compound thalassemia while it's
      specificity was 72.4% (252/348) in the non-thalassemia group. (4) With positive
      indexes of MCV, MCH and MCV + MCH, when HbA(2) > 3.5% it had a high value in beta
      thalassemia screening, but when HbA(2) < 2.5% it had little value in alpha
      thalassemia screening. (5) As a single marker, MCV and MCH had better
      sensitivity, specificity, positive predictive value, negative predictive value
      and diagnosis accuracy than HbA(2). MCV + MCH was the best for overall screening,
      but for beta thalassemia screening, MCV + MCH + HbA(2) was the best. CONCLUSIONS:
      MCV and MCH are suitable for epidemic screening in a large population, physical
      examination and premarital check-up. Hb electrophoresis and thalassemia gene
      diagnosis are recommended for subjects with positive MCV and MCH indexes.
      Diagnoses of alpha and beta-thalassemia gene are recommended for pregnant women
      with positive MCV and MCH indexes.

PMID- 22455740
TI  - [Clinical study of gasless laparoscopy in the treatment of benign ovarian tumor
      in 10 pregnant women].
AB  - OBJECTIVE: To investigate the feasibility, safety and effect of gasless
      laparoscopic surgery used in patients at the second trimester. METHODS: From Aug.
      2006 to Aug. 2008, the data of 10 cases at gestational 15 - 24 weeks complicated
      by ovary benign tumors (the diameters more than 5 cm) undergoing gasless
      laparoscopic surgery were studied retrospectively. Operation time, bleeding loss,
      period of hospitalization, the status of fetus and newborn babies, and peri
      operative or postoperative complications were observed. RESULTS: All 10 cases
      were treated by gasless laparoscopic surgery, including 4 cases with mature
      teratoma, 5 cases with epithelial tumors and 1 case with ovarian endometrioma.
      The mean time of surgery was (30 +/- 5) minutes, the mean bleeding in the surgery
      was (30 +/- 8) ml, the mean period of in hospitalization was (6 +/- 2) days. The
      blood gas (pH: 7.42 +/- 0.11, 7.41 +/- 0.18, 7.42 +/- 0.12), blood pressure [mean
      arterial pressure (MAP): (90.4 +/- 3.1), (90.6 +/- 0.7), (89.7 +/- 0.8) mm Hg (1
      mm Hg = 0.133 kPa)] and heart rates [(84.0 +/- 1.6), (84.3 +/- 1.7), (82.7 +/-
      1.1) bpm] in all cases at pre, peri and postoperative time did not show
      statistical difference (P all > 0.05). The fetal hearts were all in the normal
      range preoperative, intraoperative and postoperative time (P > 0.05). No
      perioperative and postoperative complications were observed. All the cases
      underwent term delivery. Fetal weight and Apgar score did not show abnormality.
      CONCLUSION: Gasless laparoscopic surgery at the second trimester is feasible and
      safe to mother and fetus.

PMID- 22455741
TI  - [Factors and neonatal outcomes associated with histologic chorioamnionitis after
      premature rupture of membranes in the preterms].
AB  - OBJECTIVE: To investigate factors and neonatal outcomes associated with
      histologic chorioamnionitis (HCA) in preterm premature rupture of membranes
      (PPROM). METHODS: From Jan. 2008 to Jun. 2011, 230 women with PPROM at 28 -
      33(+6) weeks of gestation undergoing deliveries in the Second Affiliated Hospital
      of Wenzhou Medical College were studied retrospectively. According to placental
      histopathologic findings, those patients were categorized into two groups,
      including 138 cases in histologic chorioamnionitis (HCA group) and 65 cases in
      non-chorioamnionitis (control) group. Age, parity, gestational age of PPROM and
      delivery, latency period, oligohydramnios, white blood cell (WBC) count and serum
      C-reactive protein (CRP) level at admission and before delivery, the incidence of
      neonatal respiratory distress syndrome (NRDS), neonatal pneumonia,
      bronchopulmonary dysplasia, necrotizing enterocolitis, early-onset neonatal
      sepsis, abnormal brain sonography findings and mortality were compared between
      two groups. RESULTS: (1) The incidence of HCA was 68.0% (138/203) in all 203
      cases with PPROM. (2) The occurring ruptured membrane gestation in HCA group was
      (31.1 +/- 1.5) weeks, which were significantly earlier than (32.0 +/- 1.3) weeks
      in control group (P < 0.05). The level of CRP of (8.2 +/- 14.9) mg/L before
      delivery in HCA group was significantly higher than (5.5 +/- 7.2) mg/L in control
      group (P < 0.05). The rate of oligohydramnios and cesearean sections were 55.1%
      (76/138) and 45.7% (63/138) in HCA group, which were significantly higher than
      30.8% (20/65) and 29.2% (19/65) in control group (P < 0.05). There were no
      significant difference in patient's age, parity, WBC count and CRP at admission
      between two groups (P > 0.05). The latency period did not show significant
      difference between (140 +/- 116) hours in HCA group and (129 +/- 125) hours in
      control group (P > 0.05). (3) Using multivariable logistic regression models,
      oligohydramnios (OR = 2.937), gestational age of PPROM < 32 weeks (OR = 2.352),
      serum CRP level > 8 mg/L before delivery (OR = 4.923) and latency period > 48 -
      168 hours (OR = 4.439) were significantly associated with HCA (P < 0.05). (4) The
      gestational age of delivery and birth weight of HCA group were significantly
      lower than those of control group [(32.0 +/- 1.5) weeks vs. (32.7 +/- 1.5) weeks,
      (1680 +/- 379) g vs. (2017 +/- 333) g, respectively, P < 0.05]. The incidence of
      Apgar < 7, abnormal brain sonograhy findings, neonatal pneumonia,
      bronchopulmonary dysplasia, early-onset neonatal sepsis and mortality in HCA
      group were significantly higher than those in control group [20.3% (28/138) vs.
      7.7% (5/65), 14.5% (20/138) vs. 4.6% (3/65), 12.3% (17/138) vs. 3.1% (2/65), 5.8%
      (8/138) vs. 0, 6.5% (9/138) vs. 0, 12.3% (17/138) vs. 3.1% (2/65), respectively,
      P < 0.05]. The incidence of necrotizing enterocolitis (1.5%, 2/138) in HCA group
      was higher than that of control group (0) and the incidence of NRDS (18.8%,
      26/138) in HCA group did not show statistical difference with 21.4% (14/65) in
      control group (P > 0.05). CONCLUSIONS: It was found that HCA was significantly
      correlated with lower gestational age of PPROM, higher serum CRP level before
      delivery, prolonged latency period and oligohydramnios in PPROM. HCA could
      increase the neonatal morbidity and mortality.

PMID- 22455742
TI  - [Evaluation of the clinical value of simultaneous hysterectomy and bilateral
      salpingectomy in perimenopausal women].
AB  - OBJECTIVE: To investigate the effects on pelvic pseudocyst, ovarian function and
      symptoms of peri-menopausal period in patients with benign uterine disease
      undergoing simultaneous hysterectomy and bilateral salpingectomy. METHODS: From
      Jan. 2000 to Dec. 2006, 1193 patients with benign uterine disease underwent total
      or subtotal hysterectomy, they were followed up for 48 months, 334 patients lost
      follow-up, the other 859 patients were divided into 2 groups, including 348
      patients undergoing simultaneous hysterectomy and bilateral salpingectomy in
      study group and 511 patients undergoing only hysterectomy in control group. The
      occurrence of pelvic pseudocyst and symptoms of peri-menopausal period and the
      changes of serum sexual hormone were observed. RESULTS: (1) The rate of pelvic
      pseudocyst was 1.7% (6/348) in study group, which was significantly lower than
      4.3% (22/511) in control group (P = 0.036). (2) There was an increasing trend of
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a decreasing
      trend of estradiol (E(2)) at range of 6 - 48 months after surgery. At 3 months
      after surgery, LH in study group was significantly higher than that in control
      group [(13.9 +/- 2.2) U/L vs. (12.6 +/- 2.5) U/L, P = 0.032]; FSH in study group
      at 6 months and 12 months after surgery were (17.6 +/- 2.2) U/L and (26.7 +/-
      5.0) U/L, which were significantly higher than (16.2 +/- 2.8) U/L and (24.3 +/-
      3.1) U/L in control group (P = 0.035 and P = 0.031). At 12 months after surgery,
      LH in study group of (24.1 +/- 3.0) U/L was significantly higher than (22.5 +/-
      1.8) U/L in control group (P = 0.017). E(2) in control group of (97 +/- 22)
      pmol/L was significantly lower than (109 +/- 17) pmol/L in control group at 24
      months after surgery (P = 0.028); FSH in study group was lower than that in
      control group at 48 months after surgery [(34.9 +/- 6.7) U/L vs. (38.0 +/- 4.8)
      U/L, P = 0.043]. There were no significant differences of FSH, LH, and E(2)
      between two groups at the other time points (P > 0.05). (3) At 6 months after
      surgery, the rate of perimenopausl systems of 21.8% (76/348) in study group was
      significantly higher than 15.9% (81/511) in control group (P = 0.026). However,
      at 24 months after surgery, the rate of perimenopausal symptoms of 54.4%
      (278/511) in control group was significantly higher than 47.1% (164/348) in study
      group (P = 0.036). CONCLUSION: Simultaneous hysterectomy and bilateral
      salpingectomy could decrease the occurrence of pelvic pseudocyst, and had similar
      effects on ovarian function and peri-menopausal symptoms compared with only
      hysterectomy in patients with benign uterine diseases.

PMID- 22455743
TI  - [The relationship of serum testosterone and its related index with the metabolism
      syndrome in women at perimenopausal or postmenopausal periods].
AB  - OBJECTIVE: To investigate the relationship between testosterone level and related
      index and metabolic syndrome (MS) of women in perimenopause or postmenopause
      period. METHODS: From May 2009 to August 2010, 911 women aged 40-65 years
      underwent physical examination in the Memorial Hospital, Sun Yat-sen University
      were enrolled in this study, which were divided into 175 women with early
      perimenopause period in group A, 112 women late perimenopause period in group B,
      161 women with early postmenopause period in group C, 132 women with moderate
      postmenopause period in group D, 88 women with late postmenopause period in group
      E, 243 women with regular menstruation as control group (group F). MS was defined
      according to the International Diabetes Federation (IDF) criteria. The
      relationship of free testosterone level and MS of women in different stage of
      menopause was analyzed. RESULTS: (1) Compared with 1.13 nmol/L in group F, median
      testosterone level of 1.03 nmol/L in group A, 0.91 nmol/L in group B, 0.91 nmol/L
      in group C, 0.87 nmol/L in group D, 0.83 nmol/L in group E decreased
      significantly at early peri-menopause period (P < 0.01). Median free androgen
      index (FAI) was 1.33 in group A, 1.56 in group B, 1.69 in group F. When compared
      median FAI in group A with those in group F or B, it all showed significantly
      difference (P < 0.01); Testosterone (T)/estradiol (E(2)) were 0.042 in group C,
      0.040 in group D, 0.042 in group E, 0.010 in group A. When compared T/E(2) in
      group C with group F, D and E, it all reached statistical difference (P < 0.01).
      (2) There were negative correlation among waist circumference (WC, r = -0.287),
      fasting blood glucose (FBG, r = -0.281), triglyceride (TG, r = -0.224) and sex
      hormone-binding globulin (SHBG) and positive correlation with high density
      lipoprotein cholesterone (HDL-C, r = 0.314). The logistic regression analysis for
      MS showed that the MS was associated with SHBG significantly (OR = 0.993, 95%CI:
      0.986 - 0.999, P = 0.035). (3) When cut-off value of SHBG was defined at 56.14
      nmol/L, SHBG was used to predict MS with sensitivity of 63.13% and specificity of
      69.45%. CONCLUSIONS: Serum testosterone was associated with MS in women at
      perimenopausal and postmenopausal period, so window period of preventing MS was
      set at perimenopausal period. A serum testosterone level was elevated from
      premenopause to postmenopause period. Because there was an association between
      SHBG and MS, SHBG was a selectable parameter to predict MS.

PMID- 22455744
TI  - [Influence of EmbryoGlue on the implantation of embryo and pregnancy outcome in
      vitro fertilization-embryo transfer].
AB  - OBJECTIVE: To study the influence of EmbryoGlue on the implantation of embryo and
      pregnancy outcome in vitro fertilization (IVF)-embryo transfer (ET). METHODS:
      From August 2010 to January 2011, 243 infertile patients in Reproductive Medical
      Center of Tianjin Medical University General Hospital who underwent IVF or
      intracytoplasmic sperm injection (ICSI) were divided into two groups, including
      129 cases used EmbryoGlue as the embryo transfer medium in experimental group and
      114 cases used G-2 as embryo transfer medium in control group. Pregnancy outcome
      were compared between two groups. RESULTS: (1) The female age, IVF/ICSI
      constituent ratio, previous failure cycles and infertile factors of patients did
      not show statistical difference between experimental group and control group (P >
      0.05). (2) The implantation rate of women in experimental group increased
      significantly compared with the control group [30.4% (85/280) vs. 18.8% (48/255),
      P < 0.05]; Clinical pregnancy rate increased significantly compared with the
      control group [48.8% (63/129) vs.34.2%(39/114), P < 0.05]; Multiple pregnancy
      rate increased significantly compared with the control group [34.9% (22/63) vs.
      20.5% (8/39), P < 0.05]; Ectopic pregnancy rate decreased significantly compared
      with the control group [4.8% (3/63) vs. 17.9% (7/39), P < 0.05]. CONCLUSION:
      EmbryoGlue can facilitate embryo implantation in IVF-ET and reduce the occurrence
      of ectopic pregnancy.

PMID- 22455745
TI  - [Clinical value of combined detection of serum human epididymal secretory protein
      E4 and CA(125) in the diagnosis of endometrial carcinoma].
AB  - OBJECTIVE: To explore the clinical value of combined detection of serum human
      epididymal secretory protein E4 (HE4) and CA(125) in the diagnosis of endometrial
      carcinoma. METHODS: From Jan 2010 to Apr 2011, the serum specimens were collected
      from 124 cases of endometrial carcinoma, 97 cases of benign disease of uterus and
      109 cases of healthy women. HE4 levels in the serum were detected by ELISA, and
      CA(125) levels in the serum were detected by the electro-chemiluminescent
      immunoassay. Those results were shown with median level. Accuracy of the
      diagnosis was evaluated by the area under the receiver operating characteristic
      curve (ROC-AUC). RESULTS: The median levels of HE4 and CA(125) were 78.09 pmol/L
      and 33.43 kU/L in serum of endometrial carcinoma group. The median levels of HE4
      and CA(125) were 46.37 pmol/L and 18.26 kU/L in serum of benign disease of uterus
      group. The median levels of HE4 and CA(125) were 31.75 pmol/L and 12.64 kU/L in
      serum of healthy women group. The HE4 and CA(125) levels in serum of endometrial
      carcinoma group were significantly higher than those of benign disease of uterus
      group or healthy women group (all P < 0.05). Compared with that benign disease of
      uterus group, the ROC-AUC of HE4 and CA(125) in endometrial carcinoma group were
      0.913 and 0.801, respectively. When the specificity was 95.0%, the sensitivities
      of HE4, CA(125), and combined detection of HE4 and CA(125) in endometrial
      carcinoma group were 41.1%, 22.6% and 46.0%, respectively. The positive rates of
      HE4 and CA(125) were 31% (27/86) and 12% (10/86) in stage I-II of endometrial
      carcinoma, while the positive rates were 63% (24/38) and 47% (18/38) in stage III
      IV of endometrial carcinoma, in which there were significant difference between
      patients in stage III-IV and stage I-II (P < 0.01). CONCLUSIONS: The combined
      detection of serum HE4 and CA(125) is helpful to the diagnosis of endometrial
      carcinoma. The sensitivity, specificity and early diagnosis of HE4 are better
      than that of CA(125). The positive rates of HE4 and CA(125) in endometrial
      carcinoma are related to the clinical staging.

PMID- 22455746
TI  - [MicroRNA expression and its role in the cell cycle regulation in decidualized
      endometrial stromal cells in vitro].
AB  - OBJECTIVE: To study microRNA (miRNA) expression and role of cell cycle regulation
      in decidualized endometrial stormal cells (ESC) in vitro. METHODS: ESC was
      induced decasualization in vitro and matched with non-decidualized cells as
      controls. The expression repertoire of miRNA was measured by microarray chip and
      was validated by real-time PCR. Flow cytometry was used to identify ESC cycle
      during decidual reaction in vitro and after miRNA222 inhibitor was transfected
      into it. RESULTS: (1) Between decidualized and undecidualized stromal cells,
      there were 49 miRNAs significantly different expression by microarray chip,
      including 16 miRNA up-regulation and 33 miRNA down-regulation.hsa-miR-27b, 30c,
      143, 101, 181b, 29b, 30d, 507, 23a, 222, 221 exhibited significantly differential
      expression between decicualized and undecidualized stromal cells by real-time PCR
      (P < 0.05). (2) After miRNA222 inhibitor (NC-FAM) transfection to decidual ESC,
      ESC were cultured by FBS medium for 24 hours, the rate of transfection was 70%.
      ESC were transfected with miRNA 222 inhibitor and cultured for 48 hours, the
      percentage of ESC at S-phase of (6.2 +/- 0.7)% were significantly lower than
      (10.9 +/- 0.8)% in control group (P < 0.05);the percentage of ESC at G(0)/G(1)
      phase increased at transfection group [(77.5 +/- 1.3)% vs. (73.0 +/- 1.6)% at
      control group], but there was no significant difference (P > 0.05).
      Decasualization ESC were transfected with miRNA 222 inhibitor and cultured for 48
      h, the percentage of ESC at S-phase was (3.3 +/- 0.6)% in transfection group,
      which were significantly lower than (7.8 +/- 0.9)% in control group (P < 0.05).
      The percentage of ESC at G(0)/G(1) phase was (80.7 +/- 1.6)% in transfection
      group and (74.9 +/- 1.1)%. In control group, which did not reached statistical
      difference (P > 0.05). CONCLUSION: miRNA was involved in ESC decidual process in
      vitro by regulating cell cycle.

PMID- 22455747
TI  - [Effects of PI3K/Akt/NF-kappaB signal pathway on FSH facilitation on cell
      proliferation and invasion by human epithelial ovarian cancer].
AB  - OBJECTIVE: To explore the effects of phosphatidylinositol 3-kinase (PI3K)/protein
      kinase B (Akt)/nuclear factor-kappa B (NF-kappaB) signal pathway on the process
      of follicle-stimulating hormone (FSH) facilitating cell proliferation and
      invasion in human epithelial ovarian cancer. METHODS: Ovarian cancer cell lines
      SKOV3 and 3AO were cultured to exponential phase, then assigned to control group,
      FSH group, LY294002 group and FSH + LY294002 group, respectively. Cells were
      treated with different concentration of FSH and LY294002, respectively. The
      effects of FSH on cell proliferation were observed by methylthiazolyl tetrazolium
      (MTT). Morphological changes were observed by phase contrast microscope. The
      ability of cell invasion was investigated by transwell invasion assay. The
      expression of FSH receptor (FSHR), Akt1/2, phosphorylated-Akt (p-Akt) and NF
      kappaB p65 protein were detected by western blot. RESULTS: (1) FSH could promote
      the proliferation of SKOV3 and 3AO cells. When the cells were treated with 40 U/L
      FSH for 48 hours (SKOV3) and 24 hours (3AO), compared with those in control
      groups, they reached the highest proliferation rate (P < 0.05), respectively. (2)
      The morphology of SKOV3 and 3AO cells in four groups:in control group, SKOV3
      cells were short spindle and 3AO cells were long spindle, the nuclei of them were
      both roundness or oval, the cytoplasm were bright. In FSH group, the cells
      changed to slightly longer or polygonal, they were full in shape, meanwhile, the
      cell intensity were higher than control group. In LY294002 group, some cells
      changed from spindle to round, and began to shrink. The cell intensity
      diminished. The morphology of FSH + LY294002 group was similar with control
      group, but the cell intensity was lower than that in FSH group. (3) The number of
      SKOV3 cell that passed through the membrane in control group, FSH group, LY294002
      group and FSH + LY294002 group was (26 +/- 6), (118 +/- 19), (18 +/- 5) and (38
      +/- 7), respectively. The number of 3AO cell was (19 +/- 4), (134 +/- 20), (12 +/
      3) and (58 +/- 11), respectively. The results showed that the number of cells in
      FSH group was significantly higher than that in control group (P < 0.05), while
      the number of cell in FSH + LY294002 group was significantly fewer than that in
      FSH group (P < 0.05). (4) There was no significant difference in the expression
      of FSHR and Akt1/2 between FSH group and control group (P > 0.05), but FSH
      increased the expression of p-Akt and the ratio of NF-kappaB p65 in the nucleus
      versus cytoplasm in SKOV3 and 3AO cells, there were significant differences
      compared with control group (P < 0.05). LY294002 reversed the effects of FSH on
      increasing the expression of p-Akt and the ratio of NF-kappaB p65 in the nucleus
      versus cytoplasm, there were significant differences among LY294002 group, FSH +
      LY294002 group and FSH group (P < 0.05). CONCLUSION: The effects of FSH on
      proliferation and invasion of ovarian cancer cell lines SKOV3 and 3AO may be
      realized by regulating the activity of NF-kappaB in PI3K/Akt signal pathway.

PMID- 22455748
TI  - Synthesis of the bacteriocin glycopeptide sublancin 168 and S-glycosylated
      variants.
AB  - The synthesis of sublancin 168, a unique S-glucosylated bacteriocin antibiotic,
      is described. The natural product and two S-glycosylated variants were
      successfully prepared via native chemical ligation followed by folding. The
      synthetic glycopeptides were shown to possess primarily an alpha-helical
      secondary structure by CD and NMR studies.

PMID- 22455749
TI  - Germline transmission of a novel rat embryonic stem cell line derived from
      transgenic rats.
AB  - Germline-competent rat embryonic stem (ES) cell lines are important resources for
      the creation of mutant rat models using ES-cell-based gene targeting technology.
      The ability to isolate germline-competent ES cell lines from any rat strain,
      including genetically modified strains, would allow for more sophisticated
      genetic manipulations without extensive breeding. Sprague Dawley (SD) males
      carrying an enhanced green fluorescent protein (EGFP) transgene were used as the
      founder animals for the derivation of ES cell lines. A number of ES cell lines
      were established and subjected to rigorous quality control testing that included
      assessment of pluripotency factor expression, karyotype analysis, and
      pathogen/sterility testing. Two male ES cell lines, SD-Tg.EC1/Rrrc and SD
      Tg.EC8/Rrrc, were injected into blastocysts recovered from a cross of Dark Agouti
      (DA) males with SD females. Resulting chimeric animals were bred with wild-type
      SD mates to verify the germline transmissibility of the ES cell lines by
      identifying pups carrying the ES cell line-derived EGFP transgene. While both ES
      cell lines gave rise to chimeric animals, only SD-Tg.EC1 was germline competent.
      This confirms the feasibility of deriving germline-competent ES cell lines from
      transgenic rat strains and provides a novel ES cell line with a stable green
      fluorescent protein (GFP) reporter for future genetic manipulations to create new
      rat models.

PMID- 22455750
TI  - Dispersion energy enforced dimerization of a cyclic disilylated plumbylene.
AB  - By reaction of 1,4-dipotassio-1,1,4,4
      tetrakis(trimethylsilyl)tetramethyltetrasilane with PbBr(2) in the presence of
      triethylphosphine a base adduct of a cyclic disilylated plumbylene could be
      obtained. Phosphine abstraction with B(C(6)F(5))(3) led to formation of a base
      free plumbylene dimer, which features an unexpected single donor-acceptor PbPb
      bond. The results of density functional computations at the M06-2X and B3LYP
      level of theory indicate that the dominating interactions which hold the
      plumbylene subunits together and which define its actual molecular structure are
      attracting van der Waals forces between the two large and polarizable plumbylene
      subunits.

PMID- 22455751
TI  - The long-term effect of premier pay for performance on patient outcomes.
AB  - BACKGROUND: Pay for performance has become a central strategy in the drive to
      improve health care. We assessed the long-term effect of the Medicare Premier
      Hospital Quality Incentive Demonstration (HQID) on patient outcomes. METHODS: We
      used Medicare data to compare outcomes between the 252 hospitals participating in
      the Premier HQID and 3363 control hospitals participating in public reporting
      alone. We examined 30-day mortality among more than 6 million patients who had
      acute myocardial infarction, congestive heart failure, or pneumonia or who
      underwent coronary-artery bypass grafting (CABG) between 2003 and 2009. RESULTS:
      At baseline, the composite 30-day mortality was similar for Premier and non
      Premier hospitals (12.33% and 12.40%, respectively; difference, -0.07 percentage
      points; 95% confidence interval [CI], -0.40 to 0.26). The rates of decline in
      mortality per quarter at the two types of hospitals were also similar (0.04% and
      0.04%, respectively; difference, -0.01 percentage points; 95% CI, -0.02 to 0.01),
      and mortality remained similar after 6 years under the pay-for-performance system
      (11.82% for Premier hospitals and 11.74% for non-Premier hospitals; difference,
      0.08 percentage points; 95% CI, -0.30 to 0.46). We found that the effects of pay
      for performance on mortality did not differ significantly among conditions for
      which outcomes were explicitly linked to incentives (acute myocardial infarction
      and CABG) and among conditions not linked to incentives (congestive heart failure
      and pneumonia) (P=0.36 for interaction). Among hospitals that were poor
      performers at baseline, mortality was similar in the two groups of hospitals at
      the start of the study (15.12% and 14.73%; difference, 0.39 percentage points;
      95% CI, -0.36 to 1.15), with similar rates of improvement per quarter (0.10% and
      0.07%; difference, -0.03 percentage points; 95% CI, -0.08 to 0.02) and similar
      mortality rates at the end of the study (13.37% and 13.21%; difference, 0.15
      percentage points; 95% CI, -0.70 to 1.01). CONCLUSIONS: We found no evidence that
      the largest hospital-based pay-for-performance program led to a decrease in 30
      day mortality. Expectations of improved outcomes for programs modeled after
      Premier HQID should therefore remain modest.

PMID- 22455752
TI  - Thirty-day readmissions--truth and consequences.

PMID- 22455753
TI  - Suing states over threatened access to care--the Douglas decision.

PMID- 22455754
TI  - Medicare's readmissions-reduction program--a positive alternative.

PMID- 22455755
TI  - Optimized expression of dual reporter genes in transient transfection of purified
      Toxoplasma gondii  using different promoters.
AB  - Fluorescent protein and luciferase genes are valuable reporter genes and have
      been widely used for noninvasive monitoring of gene expression in living tissues
      and cells. We tested expression of the dual reporter genes in transient
      transfection of purified  Toxoplasma gondii  tachyzoites. Two copies of the
      enhanced yellow fluorescent protein (EYFP) gene were put under the control of 3
      representative T. gondii promoters (GRA1, SAG1, and DHFR). Fluorescence from each
      EYFP reporter was significantly higher than that from a green fluorescent protein
      (GFP) reporter. The GRA1-EYFP reporter gave the highest fluorescence. Although
      both fluorescence and luciferase were expressed in the dual reporter system, the
      luciferase reporter was more efficient than either the EYFP or GFP reporters, and
      it required fewer parasites to be successfully used.

PMID- 22455756
TI  - Closely stacked oligo(phenylene ethynylene)s: effect of pi-stacking on the
      electronic properties of conjugated chromophores.
AB  - In this work, a bicyclo[4.4.1]undecane scaffold is used to hold oligo(phenylene
      ethynylene) units in a cofacially stacked arrangement along the entire length of
      the conjugated units. We study the impact that the resulting strong interchain
      interactions have on the photophysical properties. The length of the individual
      oligomer branches was varied from three to five rings to investigate the effect
      of conjugation on the electronic properties of the stacked segments. Absorption
      and fluorescence spectra were recorded and compared to those of the corresponding
      unstacked analogues. Time-dependent density functional theory calculations were
      carried out and helped to rationalize the low-energy features present in the
      fluorescence spectra of the stacked systems. The calculations indicate that the
      low-energy emissions are due to the presence of excimer-like states. The stronger
      intensity of the low-energy fluorescence band observed in the five-ring stacked
      system compared to the three-ring analogue is attributed to the smaller
      activation barrier that separates the local intrachain state and the excimer-like
      state in the former compound.

PMID- 22455757
TI  - Absence of low back pain in patients followed weekly over one year with automated
      text messages.
AB  - BACKGROUND: In order to define the onset of a new episode of low back pain (LBP),
      the definition of a "non-episode" must be clear. De Vet et al reviewed the
      scientific literature but found no evidence-based definitions of episodes or non
      episodes of LBP. However, they suggested that pain-based episodes should be
      preceded and followed by a period of at least one month without LBP. As LBP is an
      episodic disease, it is not clear whether a sufficient number of patients with
      LBP will be LBP-free for at least one month ("non-episode") to justify the use of
      this duration in the definition of pain free episode. OBJECTIVES: Two clinical
      populations were followed weekly over one year making it possible 1) to determine
      the maximum numbers in a row of weeks without LBP, 2) to determine the prevalence
      of non-episodes throughout a one-year period, and 3) to find the prevalence of
      patients who reported to be in a non-episode of LBP at the end of the study.
      METHODS: Secondary data were used from two recent clinical studies, in which
      weekly automated text messages (SMSes) had been collected on the number of days
      with LBP in the preceding week for one year. Weeks with 0 days of LBP were
      defined as "zero-weeks" and four zero-weeks in a row were defined as a period
      without LBP (a"non-episode") according to de Vet et al's suggestion. The study
      participants, all from the secondary care sector, consisted of: study 1) patients
      with LBP and Magnetic Resonance Imaging-identified Modic changes and study 2)
      patients without obvious acute disc problems, Modic changes or other pathologies,
      who therefore were assumed to have non-specific LBP. Both studies were two-armed
      intervention studies without a significant difference in outcome between
      intervention groups. The number of zero-weeks was identified in each participant.
      Thereafter the numbers of participants who reported at least one non-episode
      during the study period were identified. Finally, the numbers of participants who
      had a non-episode at the end of the study were counted. Estimates are reported
      with their 95% confidence intervals. RESULTS: The numbers of participants
      included in the analyses were 80 and 209. Most commonly, no zero weeks were
      reported, by 65% (55-75) and 56% (49-63) of patients, respectively. The
      percentages of study participants with at least one non-episode at some time
      during the course of the study were 20% (11-29) and 18% (15-21. The percentages
      of participants who were identified as being in a non-episode at the time of the
      last week of the study were, 5% (95% CI: 0-10) and 4% (1-7) respectively.
      CONCLUSIONS: The vast majority of these secondary care sector patients had a
      profile of more or less constant LBP. The estimates for non-episodes during the
      study period and at the end of the study were very similar for participants with
      LBP who also had Modic changes and those with non-specific LBP. It is possible
      that a definition of pain-free periods is pointless in patients seeking care in
      the secondary care sector.

PMID- 22455758
TI  - Usual folic acid intakes: a modelling exercise assessing changes in the amount of
      folic acid in foods and supplements, National Health and Nutrition Examination
      Survey, 2003-2008.
AB  - OBJECTIVE: The USA currently fortifies enriched cereal grain products (ECGP) with
      folic acid at 140 MUg/100 g. In addition, folic acid can be voluntarily added to
      ready-to-eat cereals (RTEC) up to 400 MUg/serving and it is found in many dietary
      supplements, most often at a dose of 400 MUg. We sought to model folic acid
      intake under various fortification and supplementation scenarios. DESIGN: The
      National Health and Nutrition Examination Survey is a population-based cross
      sectional survey representative of the non-institutionalized, civilian US
      population. Information on folic acid intake is collected in two 24 h dietary
      recalls and survey questions on dietary supplement use, which allows estimation
      of usual total folic acid intake. We modelled five different levels of folic acid
      fortification in ECGP, while varying the amounts in RTEC and dietary supplements.
      SETTING: United States. SUBJECTS: US adults (n 14 353) aged >=19 years; non
      pregnant women of childbearing age (n 4272). RESULTS: The percentage of adults
      with usual daily folic acid intake above the tolerable upper intake level of 1000
      MUg was influenced more by the typical amount in supplements, while the median
      intake was influenced more by the ECGP fortification level. By manipulating the
      amount in at least two sources, it was possible to shift the distribution such
      that more women of childbearing age consumed the recommended intake of 400 MUg of
      folic acid without increasing the percentage of adults with intake above the
      tolerable upper intake level. The results varied among population subgroups.
      CONCLUSIONS: Our results suggest that combined strategies are required to meet
      population recommendations for folic acid intake.

PMID- 22455759
TI  - Clinicians' adherence versus non adherence to practice guidelines in the
      management of patients with sarcoma: a cost-effectiveness assessment in two
      European regions.
AB  - BACKGROUND: Although the management of sarcoma is improving, non adherence to
      clinical practice guidelines (CPGs) remains high, mainly because of the low
      incidence of the disease and the variety of histological subtypes. Since little
      is known about the health economics of sarcoma, we undertook a cost-effectiveness
      analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing
      costs and outcomes when clinicians adhered to CPGs and when they did not.
      METHODS: Patients studied had a histological diagnosis of sarcoma, were older
      than 15 years, and had been treated in the Rhone-Alpes region of France (in
      2005/2006) or in the Veneto region of Italy (in 2007). Data collected
      retrospectively for the three years after diagnosis were used to determine
      relapse free survival and health costs (adopting the hospital's perspective and a
      microcosting approach). All costs were expressed in euros (?) at their 2009
      value. A 4% annual discount rate was applied to both costs and effects. The
      incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse
      free year gained when management was compliant with CPGs compared with when it
      was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity
      analysis was performed based on a non-parametric bootstrap method. RESULTS: A
      total of 219 patients were included in the study. Compliance with CPGs was
      observed for 118 patients (54%). Average total costs reached 23,571 euros when
      treatment was in accordance with CPGs and 27,313 euros when it was not. In
      relation to relapse-free survival, compliance with CPGs strictly dominates non
      compliance, i.e. it is both less costly and more effective. Taking uncertainty
      into account, the probability that compliance with CPGs still strictly dominates
      was 75%. CONCLUSIONS: Our findings should encourage physicians to increase their
      compliance with CPGs and healthcare administrators to invest in the
      implementation of CPGs in the management of sarcoma.

PMID- 22455760
TI  - Protein structure validation using side-chain chemical shifts.
AB  - We present a method of assessing the quality of protein structures based on the
      use of side-chain NMR chemical shifts. Because these parameters are very accurate
      reporters of side-chain positions and are highly sensitive to tertiary structure
      and packing, they are particularly useful for structure validation. To analyze a
      given structure, we define a quality score, QCS, that compares the chemical
      shifts calculated from such a structure with the corresponding experimental
      values in a way that takes account of the errors in the calculations. The results
      that we report illustrate the advantages in the examination of the quality of
      protein structures from the perspective of side-chains. 

PMID- 22455762
TI  - Absorption, distribution, metabolism and excretion of [14C]dexlansoprazole in
      healthy male subjects.
AB  - BACKGROUND AND OBJECTIVE: The proton pump inhibitor dexlansoprazole is a modified
      release formulation of dexlansoprazole, an enantiomer of lansoprazole, which
      employs a Dual Delayed ReleaseTM (DDR) delivery system. This study was conducted
      in healthy subjects to assess the absorption, distribution, metabolism and
      excretion of a 60 mg dose of [14C]dexlansoprazole. METHODS: After multiple daily
      doses of dexlansoprazole DDR for 4 days followed by a single dose of
      [14C]dexlansoprazole on day 5, absorption, distribution, metabolism and
      elimination of [14C]dexlansoprazole were assessed in six healthy male subjects
      whose CYP (cytochrome P450) 2C19 metabolizer status was also determined. RESULTS:
      Five subjects were phenotyped as extensive metabolizers (EMs) and one subject was
      a poor metabolizer (PM). Recovery of radioactivity in urine and faeces averaged
      98% after 7 days (51% in urine and 48% in faeces) post-14C dosing. In plasma,
      dexlansoprazole was the largest component detected, with the main metabolites in
      the EM subjects being 5-glucuronyloxy dexlansoprazole and 5-hydroxy
      dexlansoprazole (CYP2C19 mediated), whereas the PM subject had greater amounts of
      dexlansoprazole sulfone (CYP3A mediated). Dexlansoprazole was not detected in
      urine; six metabolites were identified accounting for an average of 86% of the
      urinary radioactivity, with 5-glucuronyloxy dexlansoprazole, 5-glucuronyloxy
      dexlansoprazole sulfide, 2-S-N-acetylcysteinyl benzimidazole and 5-sulfonyloxy
      dexlansoprazole sulfide being the primary metabolites. In faeces, parent drug and
      six identified metabolites accounted for 23% and 72%, respectively, of the faecal
      radioactivity, with 5-hydroxy dexlansoprazole sulfide and dexlansoprazole sulfide
      being predominant. CONCLUSION: Overall, the results indicate that
      [14C]dexlansoprazole was well absorbed and extensively metabolized by oxidation,
      reduction and conjugation to 13 identified metabolites.

PMID- 22455763
TI  - [Work steadfastly and advance steadily].

PMID- 22455764
TI  - [Be practical and innovative, to promote the scientific research on vertiginous
      disease in both basic and clinical aspects].

PMID- 22455765
TI  - [Frequency characteristics of the semicircular canals lesion in Hunt syndrome
      with vertigo].
AB  - OBJECTIVE: To research the frequency characteristics of the semicircular canals
      lesion in Hunt syndrome with vertigo and the clinical value of the video head
      impulse test (vHIT) for vestibular function evaluated in this disease. METHODS:
      Thirty normal persons (control group) accepted the vHIT, 26 patients with Hunt
      syndrome with vertigo (study group) accepted low, mid and high frequency
      vestibular function tests, including caloric test (CT), head shaking test (HST)
      and vHIT. The parameters of the unilateral weakness (UW), head shaking nystagmus
      (HSN) and video head impulse test gain (vHIT-G) were observed. The correlations
      and characteristics of the results of the three tests in Hunt syndrome with
      vertigo deal were analyzed with SPSS 16.0 software. RESULTS: The values of vHIT-G
      of the six groups semicircular canal in the control group were normal
      distribution without statistical significance (F = 0.005, P < 0.01), two sides
      anterior, horizontal and posterior semicircular canals vHIT-G average (x +/- s)
      were (16.80 +/- 9.80)%, (16.57 +/- 10.30)%, (16.52 +/- 11.12)% respectively; in
      the study group the separately vHIT-G of the three canals of the affected side
      were (46.96 +/- 34.54)%, (75.35 +/- 35.29)% and (41.65 +/- 32.87)%, in which
      statistical significance comparing with the control group was detected (all P <
      0.01); the positive one of the three tests vHIT, HSN and CT were 23 cases
      (88.46%), 22 cases (84.61%) and 24 cases (92.31%), bilateral exact probability
      chi2 test all the P > 0.05;there were Positive correlation between UW and the
      vHIT-G of lateral semicircular canal (r = 0.692, P < 0.01). CONCLUSIONS: The
      vestibular lesion of Hunt syndrome with vertigo is almost complete or multiple
      frequency, which is characterized by the reduced or even aborted nerve
      conduction. Therefore, vHIT can be ultimately used for the screening test
      evaluating due to the vestibular function in Hunt syndrome with vertigo.

PMID- 22455766
TI  - [Functional analysis of the vertical semicircular canal using vertical plane
      swing test and study of its normal values].
AB  - OBJECTIVE: The purpose of this study was to set up a method to analyze the
      vertical semicircular canal function and study the normal values of the vertical
      semicircular canal function using the vertical plane swing test. METHODS: A
      prospective analysis of 100 normal persons (aged from 18 to 59 years), who were
      treated by using the vertical plane swing test with the newly developed automatic
      vestibular function diagnosis and therapy system (SRM-IV). These persons were
      rotated 180 degrees  at a sinusoidal speed (acceleration 45 degrees /s, maximum
      speed 90 degrees /s) in the vertical semicircular canal plane. Using a PC, evoked
      vertical nystagmus was analyzed in order to evaluate the excitability of vertical
      semicircular canals, including the number and the duration of nystagmus, the slow
      phase velocity and other parameters. Meanwhile, the all persons were divided into
      two groups, order and younger than 45 years respectively. In the test procedure,
      with the two pairs of the right anterior vertical semicircular canal and left
      posterior vertical semicircular canal (RALP) as well as the left anterior
      vertical semicircular canal and the rear right vertical semicircular canals
      (LARP), the average slow phase velocity of the vertical nystagmus and the canal
      paresis (CP) of the two pairs of vertical semicircular canals were calculated
      using PC and SPSS13.0 software for statistical analysis. RESULTS: There was no
      significant difference between the two groups (P > 0.05). The general CP of RALP
      was 10.2% +/- 7.1%, and LARP was 10.4% +/- 6.2%. The normal CP range of the
      vertical semicircular canal in the health group was identified (idea: <= 20%;
      normal high: 20% - 25%). CONCLUSION: The 180 degrees  vertical plane sinusoidal
      swing method is effective in functional analysis of the vertical semicircular
      canal, it is expected to be reliably used in clinical treatment.

PMID- 22455767
TI  - [Characteristics of the air-conducted ocular evoked myogenic potential in the
      young normal Chinese subjects].
AB  - OBJECTIVE: To identify the characteristics of the air-conducted ocular vestibular
      evoked myogenic potential (oVEMP) in the young normal Chinese subjects. METHODS:
      Twenty five normal subjects were recruited for conventional examinations of
      oVEMP. The subjects were 19 - 45 years of age [(24.3 +/- 5.6) years], 12 males
      and 13 females. 500 Hz air-conducted tone burst was employed for examination. The
      threshold of oVEMP in each ear was examined; patterns of these waves were
      observed and the normal ranges of the oVEMP waves responded to 100 dBnHL were
      calculated. RESULTS: All subjects were elicited with normal oVEMP N1-P1 waves in
      both ears. The response rate in these subjects was 100%. The threshold of oVEMP
      examination was (86.6 +/- 3.6) dBnHL (x(-) +/- s), latency N1 (10.1 +/- 0.4) ms,
      latency P1 (14.7 +/- 1.2) ms, interval N1-P1 (4.5 +/- 1.0) ms, amplitude (7.9 +/-
      4.4) uV. CONCLUSIONS: Air-conducted oVEMP is a kind of vestibular-ocular reflex
      respond to intensive sound generated by otolithic vestibular end organs. It is
      stable in the young normal subjects with minor variabilities.

PMID- 22455769
TI  - [The hotspot of the 30th European Academy of allergy and clinical immunology].

PMID- 22455768
TI  - [Evaluation of exposure and sensitization to house dust mites among rhinitis
      patients in the steppe environment of Inner Mongolia].
AB  - OBJECTIVE: To evaluate the correlation of exposure and sensitization to house
      dust mites among rhinitis patients, and the consistency of skin prick test (SPT)
      and serum specific IgE (sIgE) in the detection of sensitization in a steppe
      environment of inner Mongolia. METHODS: Three hundreds and fourteen patients with
      rhinitis symptoms were recruited in this study in a hospital setting at Xilinhot
      City, inner Mongolia. All patients underwent medical history investigation,
      anterior rhinoscopy, and allergen tests in vivo (SPT) and in vitro (sIgE). Dust
      samples were collected from mattresses in patient's bedroom. The concentrations
      of group I major allergen of Dermatophagoides pteronyssinus (Der p) and
      Dermatophagoides farinae (Der f) were measured by enzyme linked immunosorbent
      assay (ELISA). Statistical analysis was performed using a SPSS 17.0 software (t
      test, chi(2) test and so on). RESULTS: Among a total of 314 patients, the
      prevalence of positive SPT for Der p and Der f was 5.7% and 22.0%, respectively;
      and the prevalence of positive sIgE for Der p and Der f was 9.2% and 7.6%,
      respectively. Sensitization rates for house dust mites (Der p and/or Der f) were
      lower than those of pollens. The pollen allergen with the highest positive rate
      was mugwort (SPT, 51.9%; sIgE, 47.1%). Diagnostic tests using SPT as the gold
      standard for sensitization showed that the positive likelihood ratio of sIgE was
      4.27 for Der p and 10.64 for Der f, and the Kappa value was 0.20 for Der p and
      0.35 for Der f, respectively. A total of 276 dust samples collected from
      patient's mattresses were measured. The concentrations of Der p 1 and Der f1 were
      detectable in 2 (0.7%) and 4 (1.4%) mattress samples, respectively. There was
      positive correlation between the exposure levels of Derp 1 and the SPT positive
      reaction to Der p (r(s) = 0.156, P = 0.01), but no significant correlation was
      found between the exposure levels of Der p 1 and the sIgE positive reaction to
      Der p (r(s) = 0.116, P = 0.055). There was no significant correlation between the
      exposure levels of Der f 1 and the SPT as well as sIgE positive reaction to Der f
      1(r(s) = 0.05, P = 0.931; r(s) = 0.07, P = 0.245). CONCLUSIONS: In the steppe
      environment of inner Mongolia, exposure to house dust mites are very low, and the
      Der p and Der f are not the major allergens in patients with allergic rhinitis.
      Also, it was not a simple dose-response relationship between exposure and
      sensitization to house dust mites. In such a specific environment, there is lower
      consistency between the results of SPT and sIgE in the detection of sensitization
      to house dust mites. Therefore, it is recommended that the allergen testing in
      vivo and in vitro should be combined for clinical diagnosis.

PMID- 22455770
TI  - [Endoscopic transnasal prelacrimal recess-maxillary sinus approach for tumors in
      the pterygopalatine fossa].
AB  - OBJECTIVE: To explore the application of endoscopic transnasal prelacrimal recess
      maxillary sinus approach in surgery for lesions in the pterygopalatine fossa.
      METHODS: Five patients with tumors of pterygopalatine fossa were treated by
      endoscopic transnasal prelacrimal recess-maxillary sinus surgery between May 2008
      and May 2011. The lesions treated included 4 schwannoma. and 1 neurofibroma. The
      operation began with endoscopic transnasal lateral nasal wall approach to
      maxillary sinus. Then after opening posterior wall of maxillary sinus, the
      pterygopalatine fossa was entered and the tumor was removed. The operation was
      performed under hypotension anaesthesia. RESULTS: The tumors were removed totally
      in all 5 patients. No complication was found. After the surgery, all patients
      fully recovered and were discharged from the hospital in 5 to 12 days. No
      recurrence and death occurred during the follow up periods ranging from 5 to 28
      months. CONCLUSIONS: Endoscopic transnasal prelacrimal recess-maxillary sinus
      approach is safe and effective management for benign tumors in the
      pterygopalatine fossa. This approach reserved nasolacrimal duct and turbinate,
      maintained the structure and function of the nose, with decreased morbidity and
      shorter recovery periods.

PMID- 22455771
TI  - [Resection of petrous apex cholesteatoma via endoscopic trans-sphenoidal
      approach].
AB  - OBJECTIVE: To introduce our experience of resection of petrous apex cholesteatoma
      through endoscopic, transnasal, trans-sphenoidal approach in 3 cases, and present
      a surgical technique of intracystic resection of lesion which yielded a
      relatively stable long-term outcome. METHODS: Resection of parasellar and petrous
      apex cholesteatoma via endoscopic transsphenoidal approach was performed in three
      patients between 2001 and 2006. Surgical technique was as follows: the ethmoid
      and sphenoid sinuses were opened under endoscope, the petrous apex was accessed
      by drilling skull base bone at the lateral wall of sphenoid sinus and anterior to
      the internal carotid artery, the cyst wall of cholesteatoma was incised and
      expanded, then intracystic removal of cholesteatoma was achieved by the suction,
      curette and rinsing. RESULTS: The petrous apex cholesteatoma in all 3 patients
      were removed clearly by endoscopic, transnasal, trans-sphenoidal surgery in one
      time. Before surgery, two patients with headache and orbital apex syndrome had a
      remarkable improvement just on the day after operation and completely recovered
      in 1-4 weeks. No postoperative complications happened in all three patients. All
      patients had no recurrence in symptoms and no imaging evidences of recurrence at
      a follow-up of 3 - 7 years. CONCLUSION: The petrous apex cholesteatoma around the
      parasellar region could be treated by intracystic removal via endoscopic,
      transnasal, transsphenoidal approach, without the need to strip and remove the
      cyst wall, and the long-term efficacy was reliable.

PMID- 22455772
TI  - [Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea].
AB  - OBJECTIVE: To present the surgical technique and clinical effect of transnasal
      endoscopic repair of cerebrospinal fluid (CSF) rhinorrhea. METHODS: From 1996 to
      2010, 54 patients with CSF rhinorrhea were treated with intranasal endoscopic
      surgery, including 25 patients with traumatic CSF rhinorrhea, 17 patients with
      spontaneous CSF rhinorrhea, and 12 patients with iatrogenic CSF rhinorrhea. The
      temporalis muscle, temporalis fascial, middle turbinate mucosa, nasal septum
      mucosa, inferior turbinate mucosa, fascia lata, leg muscle, abdominal fat,
      uncinate process mucosa and sinus mucosa were used to repair the fistulae.
      RESULTS: Forty-nine patients were successfully treated after the first operation,
      1 after the second attempt, 1 after the third attempt, and 1 was successfully
      treated at the second operation in other hospital, 1 stopped therapy after an
      unsuccessful repairing. One patient recurred within one and a half years after
      operation and stopped therapy. Seven patients developed complications after the
      operation (high fever in 4, high fever and transient mild coma in 1, epilepsy in
      1, pneumocephalus in 1) and were cured afterwards. CONCLUSIONS: Transnasal
      endoscopic surgery is safe, effective and microinvasive treatment for patients
      with CSF rhinorrhea, it is the first choice for repairing of CSF rhinorrhea for
      its high successful rate. Accurate leakage site identification, selection of
      suitable approach and repairing method are critical to the success of operation.

PMID- 22455773
TI  - [Effect of jaw forward distance on forced inspiratory airflow in patients with
      obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To study the effect of different jaw forward distance on forced
      inspiratory airflow(FIF) in non-apnea subjects and patients with obstructive
      sleep apnea hypopnea syndrome (OSAHS) and to evaluate the effective jaw forward
      distance for the treatment of OSAHS with the oral appliance. METHODS: FIF was
      measured in 18 non-apnea subjects and 18 OSAHS patients at supine and lateral
      body positions with different jaw forward distances (the percentages of maximum
      jaw forward distance): 0%, 25%, 50% and 75%. FIF were converted to percentage
      values (FIF%, x(-) +/- s) followed by averaged. Then the results were analyzed by
      one-way analysis of variance and paired t-test with alpha = 0.05. RESULTS: For
      non-apnea subjects, there was no significant difference in the FIF values between
      different jaw forward distances as well as different body positions. For OSAHS
      patients, the mean FIF% at supine and lateral body positions were 107.1% +/-
      29.0% and 112.0% +/- 33.1% at jaw forward 50%, and were 106.4% +/- 20.7% and
      116.8% +/- 36.4% at jaw forward 75%, respectively, which were significantly
      higher than those (84.0% +/- 18.3% and 98.3% +/- 24.0%) at jaw forward 0% or
      those (92.7% +/- 21.8% and 103.7% +/- 22.6%) at jaw forward 25%, respectively.
      But there was no statistical difference in FIF between the two groups of jaw
      forward 50% and jaw forward 75% and no statistical difference in FIF between
      supine and lateral body positions in the same forward position. CONCLUSION: Jaw
      forward 50% is a effective jaw forward distance by oral appliance for the
      treatment of OSAHS and can improve the airway ventilation in OSAHS patients.

PMID- 22455774
TI  - [Clinical analysis of squamous cell carcinoma of the subglottis].
AB  - OBJECTIVE: To investigate the clinical characteristics, pattern of lymph node
      metastasis, optimal management and relative prognostic factors of subglottic
      squamous cell carcinoma. METHODS: A retrospective review was conducted in 36
      cases with subglottic squamous cell carcinoma from 1970 to 2005. TNM staging
      showed 6 patients with stage I, 9 stage II, 8 stage III and 13 stage IV (AJCC
      2010). Eight of these 36 cases were treated with radiotherapy alone, 18 with
      surgery alone and 10 with surgery plus perioperative radiotherapy. The overall 5
      year survival rate was estimated by the Kaplan-Meier method according to
      different clinical stages and treatments. Log-Rank analysis was used to identify
      the prognostic factors. RESULTS: The overall 5-year survival rate was 58.2%, and
      5-year survival rates were 66.7%, 66.7%, 62.5% and 30.8% for patients with stage
      I, II, III and IV, respectively, and the rates were 43.8%, 66.7% and 51.9% for
      radiotherapy alone, surgery alone, surgery plus perioperative radiotherapy,
      respectively. The 5-year survival rate of patients with stage I-III was
      significantly higher than that of patients with stage IV (chi(2) = 3.955, P <
      0.05). Pathologically confirmed positive rate of cervical lymph node was 25.0%
      (9/36), and the positive cervical lymph nodes were mainly distributed in level
      VI, followed by level II. The 5-year survival rate of patients with negative
      cervical lymph node was significantly higher than that of patients with positive
      cervical lymph node (chi(2) = 6.466, P < 0.05). CONCLUSIONS: The prognosis of
      subglottic squamous cell carcinoma was relatively poor. Total laryngectomy was
      the the main therapeutic management, and only part of the early cases could be
      treated with radiotherapy alone or partial laryngectomy. For locally advanced
      cases, the typical neck dissection including level II-IV and VI should be
      performed.

PMID- 22455775
TI  - [Diagnosis and treatment of the primary parapharyngeal space tumors].
AB  - OBJECTIVE: To study the clinical characteristics, diagnosis and surgical
      managements of the parapharyngeal space tumors. METHODS: A retrospective study of
      40 patients with primary parapharyngeal space tumors treated from January 2006 to
      December 2008 in Chinese PLA General Hospital was performed. Among the 40
      patients, there were male 22 patients, female 18 (45%), age ranged from 1 - 77,
      median 42 years old. CT scan combined with MRI was helpful to diagnose the
      parapharyngeal space tumor and make surgical plan. The surgical approaches
      include: trans-oral in 1 patient, trans-cervical approach in 22, transcervical
      parotid approach in 8, vertical ramus osteotomy approach in 1, transcervical
      partial bone resection in the angle of mandible in 4, transparotid approach in 2,
      and transcervical in combination with post auricle craniotomy approach in 2.
      RESULTS: All 40 patients had undergone surgical treatment. Postoperative
      histopathology showed benign in 28 patients and malignant in 12 patients. The
      tumors originating from salivary glands were in 15 patients, neurogenic tumors in
      12 patients and tumors originating from other tissues were in 13 patients.Among
      28 patients with benign tumors, 23 had been cured with one operation, without
      recurrence during following-up of 13 - 47 months, with a median of 39 months.
      Among 12 patients with malignant tumors, 6 patients alive (with following-up of
      24 - 50 months and a median of 36 months), 3 patients died in half year after
      operation and 3 patients lost. The post-operative complication included
      Cerebrospinal fluid leak in one patient, operative field infection in 2 patients,
      and vagus nerve injury in 3 patients. CONCLUSIONS: Surgery is the first choice
      for parapharyngeal space tumors. Transcervical approach alone can apply to most
      tumors and a broader approach is indicated for malignant or large benign tumors.
      The prognosis is good for the benign lesions, but poor for the malignant tumors.

PMID- 22455776
TI  - [EphA2 promotes angiogenesis and metastasis of head and neck squamous cell
      carcinoma in vivo].
AB  - OBJECTIVE: To investigate the effects of EphA2 on the angiogenesis and cervical
      lymph node metastasis of squamous cell carcinoma of the head and neck (SCCHN) in
      vivo. METHODS: EphA2 short hairpin (shRNA) lentiviral particles were used to
      knockdown the expression of EphA2 in SCCHN cell line M2 with high lymph nodes
      metastasis rate. Stable clones, obtained by puromycin screening, were assayed by
      RT-PCR and Western blot to validate the gene silencing efficiency and were used
      to establish SCCHN metastatic xenograft mouse model. Hematoxylin-eosin staining
      was applied to identify cervical lymph node metastasis of SCCHN in xenografted
      tumors. Immunohistochemistry was used to observe microvessel density. Western
      blot was used to investigate the protein expressions of EphA2 and vascular
      endothelial, growth factor (VEGF). RESULTS: EphA2 shRNA lentiviral particles
      efficiently decreased the mRNA and protein expressions of EphA2 in SCCHN cell
      line M2, which were further successfully utilized to establish SCCHN metastatic
      xenograft mouse model. Compared with xenografted tumors in control group,
      xenografted tumors in M2EphA2RNAi(+) group decreased significantly tumor volume
      [(430.7 +/- 190.0) mm(3) (x(-) +/- s) vs (1179.0 +/- 289.4) mm(3)] and weight
      [(0.26 +/- 0.10) g vs (0.54 +/- 0.12) g] (both P < 0.05). More importantly,
      bilateral cervical lymph node metastasis rate in M2EphA2RNAi(+) was also greatly
      declined (Mann-Whitney U = 10.0, P < 0.05). Decreased protein expressions of
      EphA2 and VEGF and microvessel density were observed in M2EphA2RNAi(+) group (t =
      26.751, P < 0.01). CONCLUSIONS: Knockdown of EphA2 expression led to the
      inhibition of tumor growth and metastasis in SCCHN nude mouse model. More
      importantly, SCCHN angiogenesis was also impeded, which might be associated with
      the decreased expression of VEGF.

PMID- 22455777
TI  - [Suppression of Aurora-A by RNA interference inhibits laryngeal cancer Hep-2 cell
      growth].
AB  - OBJECTIVE: To investigate the effects of knockdown of Aurora-A by RNA
      interference on laryngeal cancer Hep-2 cell growth in vitro and in vivo. METHODS:
      A plasmid containing siRNA against Aurora-A was constructed and transfected into
      human laryngeal cancer cell line Hep-2. Measurements included the CCK-8 assay for
      viability and proliferation, Transwell assay for invasion, colony formation assay
      for cell anchorage-independent growth. Western blot and immunohistochemistry
      assay for protein expression. Tumorigenicity was observed in vivo. RESULTS: In
      Hep-2 cells transfected by Aurora-A siRNA (designated as siRNA-3), protein
      expression of Aurora-A was suppressed by 52%. In CCK-8 assay, absorbance value of
      siRNA-3 cells (3.268 +/- 0.106, (x(-) +/- s)) was lower than that of Hep-2 cells
      (3.722 +/- 0.152, F = 17.634, P < 0.001). In Transwell assay, the average
      invasive cells per field in siRNA-3 cells (110.0 +/- 18.0) was less than that in
      Hep-2 cells (236.0 +/- 26.0, F = 26.462, P < 0.01). In colony formation assay,
      the average colony number of siRNA-3 cells (31.0 +/- 6.6) was lower than that of
      Hep-2 cells (104.0 +/- 14.0). The average tumor size in siRNA-3 group was (127.77
      +/- 174.83) mm(3), which was less than Hep-2 cell group (837.26 +/- 101.80)
      mm(3), (F = 28.187, P < 0.001). Silencing of Aurora-A decreased the expression of
      focal adhesion kinase (FAK) and matrix metalloproteinase-2 (MMP-2), key
      regulators in cell adhesion and invasion. CONCLUSIONS: The knockdown of Aurora-A
      inhibits the growth and invasiveness of Hep-2 cells in vitro and in vivo, which
      may be a promising therapeutic strategy for LSCC.

PMID- 22455778
TI  - [Repairing of palatum durum defects following maxillectomy using nasal septum
      tissue flap].
AB  - OBJECTIVE: To discuss the effect of repairing of palatum durum defects following
      maxillectomy using nasal septum tissue flap. METHODS: Twenty-six patients
      underwent maxillectomy and the defects were repaired by using full (16 cases) and
      partial (10 cases) nasal septum tissue flaps. RESULTS: Twenty-one patients were
      healed by first intention, recovering swallowing and pronunciation function. Five
      patients suffered from fistula holes, and 2 healed after dressing while 2 of the
      other 3 patients healed after second suturing with 1 still got a small fistula
      hole. Facial deformity include 4 exterior cheek mild concave and 6 complained
      about unsuited false teeth and no dorsal subsidence was found. The 3, 5, 10 year
      survival rate was 46.2%, 30.8% and 11.5% respectively. CONCLUSIONS: Repairing
      defects with nasal septum tissue flap has advantages. Nasal septum can not be
      invaded easily, and the material can be got with ease, with rich blood supply,
      being resistant to infection, easy to heal and less chance of leading to fistula
      holes. With the cartilage of nasal septum as support, facial deformity can be
      reduced. And the method is worth spreading and exploiting.

PMID- 22455779
TI  - [One case report of thoracic tracheal stenosis].

PMID- 22455780
TI  - [Internal jugular vein rupture caused by parapharyngeal space infection: one case
      report].

PMID- 22455781
TI  - [A case of hemorrhage of anonym after tracheotomy].

PMID- 22455782
TI  - [Five patients with Madelung's disease].

PMID- 22455783
TI  - [Leiomyosarcoma of the parotid gland: a case report].

PMID- 22455784
TI  - [Carcinoid tumors in middle ear: one case report].

PMID- 22455785
TI  - [Thyroid leiomyosarcoma: report of one cases].

PMID- 22455786
TI  - [Clinical effects of ocular vestibular evoked myogenic potentials in the
      diagnosis of vertigo].

PMID- 22455787
TI  - [Epidemiological research on dizziness].

PMID- 22455788
TI  - [Diagnosis of vascular vertigo].

PMID- 22455789
TI  - Synthesis and evaluation of analogues of estrone-3-O-sulfamate as potent steroid
      sulfatase inhibitors.
AB  - Estrone sulfamate (EMATE) is a potent irreversible inhibitor of steroid sulfatase
      (STS). In order to further expand SAR, the compound was substituted at the 2-
      and/or 4-positions and its 17-carbonyl group was also removed. The following
      general order of potency against STS in two in vitro systems is observed for the
      derivatives: The 4-NO(2) > 2-halogens, 2-cyano > EMATE (unsubstituted)>17
      deoxyEMATE > 2-NO(2) > 4-bromo>2-(2-propenyl), 2-n-propyl > 4-(2-propenyl), 4-n
      propyl > 2,4-(2-propenyl)= 2,4-di-n-propyl. There is a clear advantage in potency
      to place an electron-withdrawing substituent on the A-ring with halogens
      preferred at the 2-position, but nitro at the 4-position. Substitution with 2
      propenyl or n-propyl at the 2- and/or 4-position of EMATE, and also removal of
      the 17-carbonyl group are detrimental to potency. Three cyclic sulfamates
      designed are not STS inhibitors. This further confirms that a free or N
      unsubstituted sulfamate group (H(2)NSO(2)O-) is a prerequisite for potent and
      irreversible inhibition of STS as shown by inhibitors like EMATE and Irosustat.
      The most potent derivative synthesized is 4-nitroEMATE (2), whose IC(50)s in
      placental microsomes and MCF-7 cells are respectively 0.8 nM and 0.01 nM.

PMID- 22455790
TI  - Sarmentosamide, a novel hexadienamide from Thai soil actinomycetes.
AB  - A new hexadienamide derivative named sarmentosamide (1) was identified from the
      culture of Streptomyces sp. SBI108 isolated from Thai soil under an herb. The
      structure was elucidated on the basis of spectroscopic data, and the absolute
      configuration was determined by chemical degradation.

PMID- 22455791
TI  - Is topical diclofenac essential before and after uneventful phacoemulsification
      cataract surgery?
AB  - PURPOSE: The purpose of our study was to evaluate the effectiveness of
      preoperative and postoperative addition of topical diclofenac to
      chloramphenicol/dexamethasone in patients undergoing uneventful
      phacoemulsification cataract surgery. METHODS: Patients were randomized to (1)
      chloramphenicol 0.5%-dexamethasone 0.1%, 1 drop 4 times a day (n=41), or (2)
      chloramphenicol 0.5%-dexamethasone 0.1%, 1 drop 4 times a day, plus diclofenac
      0.1%, 1 drop 3 times a day (n=38). Patients in the second group also received
      diclofenac 0.1% for 3 days before surgery. Topical treatment was administered for
      28 days after phacoemulsification. On postoperative days 1, 14, and 28, best
      corrected visual acuity, macular thickness, endothelial cell density, and central
      corneal thickness (CCT) were measured. RESULTS: The 2 groups did not have a
      statistically significant difference for CCT, endothelial cell density, macular
      thickness, and visual acuity at the 3 time points of the follow-up period.
      CONCLUSIONS: The addition of diclofenac did not seem to offer any additional
      benefit after uneventful phacoemulsification.

PMID- 22455792
TI  - Integrated prevention of obesity and eating disorders: barriers, developments and
      opportunities.
AB  - OBJECTIVE: The serious consequences of obesity and eating disorders (ED),
      difficulties encountered in treatment and the high prevalence of these conditions
      are important reasons to develop efforts aimed at their prevention. The
      implementation of integrated interventions aimed at preventing risk factors for
      both obesity and ED constitutes a very exciting development. In the present paper
      we discuss and review the main reasons for an integrated approach to the spectrum
      of eating- and weight-related problems, which include anorexia nervosa, bulimia
      nervosa, anorexic and bulimic behaviours, unhealthy dieting practices, body
      dissatisfaction, binge-eating disorder, overweight and obesity. Given differences
      between the fields with regard to current perspectives and objectives, key
      barriers to an integrated approach to prevention are discussed. In order to show
      the possibilities of development of this approach, we review the main
      contributions made to date in the fields of both obesity and ED prevention. In
      particular, environmental approaches in the prevention of obesity and ED are
      reviewed, given their potential for preventing a broad spectrum of eating- and
      weight-related problems. Furthermore, several examples of initiatives that have
      utilized an integrated approach to prevention are discussed. DESIGN: Narrative
      review. CONCLUSIONS: We recommend a scenario in which the two fields share
      knowledge to enhance the difficult work of preventing and treating both ED and
      obesity.

PMID- 22455793
TI  - Biocatalysts and small molecule products from metagenomic studies.
AB  - The vast majority of bacteria present in environmental samples have never been
      cultured and therefore have not been exploited for the ability to produce useful
      biocatalysts or collections of biocatalysts generating interesting small
      molecules. Metagenomic libraries constructed using DNA extracted directly from
      natural bacterial communities offer access to the genetic information present in
      the genomes of these as yet uncultured bacteria. This review highlights recent
      efforts to recover both discrete enzymes and small molecules from metagenomic
      libraries.

PMID- 22455794
TI  - High prevalence of OXA-143 and alteration of outer membrane proteins in
      carbapenem-resistant Acinetobacter spp. isolates in Brazil.
AB  - Carbapenem resistance amongst Acinetobacter spp. has been increasing in the last
      decade. This study evaluated the outer membrane protein (OMP) profile and
      production of carbapenemases in 50 carbapenem-resistant Acinetobacter spp.
      isolates from bloodstream infections. Isolates were identified by API20NE.
      Minimum inhibitory concentrations (MICs) for carbapenems were determined by broth
      microdilution. Carbapenemases were studied by phenotypic tests, detection of
      their encoding gene by polymerase chain reaction (PCR) amplification, and
      imipenem hydrolysis. Nucleotide sequencing confirming the enzyme gene type was
      performed using MegaBACE 1000. The presence of OMPs was studied by sodium dodecyl
      sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and PCR. Molecular typing
      was performed using pulsed-field gel electrophoresis (PFGE). All isolates were
      resistant to carbapenems. Moreover, 98% of the isolates were positive for the
      gene encoding the enzyme OXA-51-like, 18% were positive for OXA-23-like (only one
      isolate did not show the presence of the insertion sequence ISAba1 adjacent to
      this gene) and 76% were positive for OXA-143 enzyme. Five isolates (10%) showed
      the presence of the IMP-1 gene. Imipenem hydrolysing activity was detected in
      only three strains containing carbapenemase genes, comprising two isolates
      containing the bla(IMP) gene and one containing the bla(OXA-51/OXA-23-like) gene.
      The OMP of 43 kDa was altered in 17 of 25 strains studied, and this alteration
      was associated with a high meropenem MIC (256 MUg/mL) in 5 of 7 strains without
      43 kDa OMP. On the other hand, decreased OMP 33-36 kDa was found in five strains.
      The high prevalence of OXA-143 and alteration of OMPs might have been associated
      with a high level of carbapenem resistance.

PMID- 22455795
TI  - Imidazol(in)ium hydrogen carbonates as a genuine source of N-heterocyclic
      carbenes (NHCs): applications to the facile preparation of NHC metal complexes
      and to NHC-organocatalyzed molecular and macromolecular syntheses.
AB  - Anion metathesis of imidazol(in)ium chlorides with KHCO(3) afforded an easy one
      step access to air stable imidazol(in)ium hydrogen carbonates, denoted as
      [NHC(H)][HCO(3)]. In solution, these compounds were found to be in equilibrium
      with their corresponding imidazol(in)ium carboxylates, referred to as N
      heterocyclic carbene (NHC)-CO(2) adducts. The [NHC(H)][HCO(3)] salts were next
      shown to behave as masked NHCs, allowing for the NHC moiety to be readily
      transferred to both organic and organometallic substrates, without the need for
      dry and oxygen-free conditions. In addition, such [NHC(H)][HCO(3)] precursors
      were successfully investigated as precatalysts in two selected organocatalyzed
      reactions of molecular chemistry and polymer synthesis, namely, the benzoin
      condensation reaction and the ring-opening polymerization of d,l-lactide,
      respectively. The generation of NHCs from [NHC(H)][HCO(3)] precursors occurred
      via the formal loss of H(2)CO(3)via a concerted low energy pathway, as
      substantiated by Density Functional Theory (DFT) calculations.

PMID- 22455796
TI  - Purification and characterization of azurin from the methylamine-utilizing
      obligate methylotroph  Methylobacillus flagellatus  KT.
AB  - Methylamine dehydrogenase (MADH) and azurin were purified from the periplasmic
      fraction of the methylamine-grown obligate methylotroph Methylobacillus
      flagellatus KT. The molecular mass of the purified azurin was 16.3 kDa, as
      measured by SDS-PAGE, or 13 920 Da as determined by MALDI-TOF mass spectrometry.
      Azurin of M. flagellatus KT contained 1 copper atom per molecule and had an
      absorption maximum at 620 nm in the oxidized state. The redox potential of azurin
      measured at pH 7.0 by square-wave voltammetry was +275 mV versus normal hydrogen
      electrode. MADH reduced azurin in the presence of methylamine, indicating that
      this cupredoxin is likely to be the physiological electron acceptor for MADH in
      the electron transport chain of the methylotroph. A scheme of electron transport
      functioning in M. flagellatus KT during methylamine oxidation is proposed.

PMID- 22455797
TI  - Body weight-dependent pharmacokinetics of busulfan in paediatric haematopoietic
      stem cell transplantation patients: towards individualized dosing.
AB  - BACKGROUND AND OBJECTIVES: The wide variability in pharmacokinetics of busulfan
      in children is one factor influencing outcomes such as toxicity and event-free
      survival. A meta-analysis was conducted to describe the pharmacokinetics of
      busulfan in patients from 0.1 to 26 years of age, elucidate patient
      characteristics that explain the variability in exposure between patients and
      optimize dosing accordingly. PATIENTS AND METHODS: Data were collected from 245
      consecutive patients (from 3 to 100 kg) who underwent haematopoietic stem cell
      transplantation (HSCT) in four participating centres. The inter-patient, inter
      occasion and residual variability in the pharmacokinetics of busulfan were
      estimated with a population analysis using the nonlinear mixed-effects modelling
      software NONMEM VI. Covariates were selected on the basis of their known or
      theoretical relationships with busulfan pharmacokinetics and were plotted
      independently against the individual pharmacokinetic parameters and the weighted
      residuals of the model without covariates to visualize relations. Potential
      covariates were formally tested in the model. RESULTS: In a two-compartment
      model, body weight was the most predictive covariate for clearance, volume of
      distribution and inter-compartmental clearance and explained 65%, 75% and 40% of
      the observed variability, respectively. The relationship between body weight and
      clearance was characterized best using an allometric equation with a scaling
      exponent that changed with body weight from 1.2 in neonates to 0.55 in young
      adults. This implies that an increase in body weight in neonates results in a
      larger increase in busulfan clearance than an increase in body weight in older
      children or adults. Clearance on the first day was 12% higher than that of
      subsequent days (p < 0.001). Inter-occasion variability on clearance was 15%
      between the 4 days. Based on the final pharmacokinetic-model, an individualized
      dosing nomogram was developed. CONCLUSIONS: The model-based individual dosing
      nomogram is expected to result in predictive busulfan exposures in patients
      ranging between 3 and 65 kg and thereby to a safer and more effective
      conditioning regimen for HSCT in children.

PMID- 22455798
TI  - Protective effects of ulinastatin on pulmonary damage in rats following scald
      injury.
AB  - Organ protection is desirable in severe burn/scald injuries, and damage
      mechanisms and thus effective therapies following scald injury have not been
      fully elucidated. Our aim was to examine the beneficial effects of ulinastatin on
      pulmonary damage associated with scald injury. Lewis rats were subjected to 30%
      total body surface area (TBSA) scald injury and were randomly divided into a burn
      control (S group) and an ulinastatin-treated group (U group). Lung
      malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined, and
      the lungs were examined histologically with immunohistochemistry (IHC) as well
      for the major histocompatibility complex (MHC) class I chain-related antigen A
      (MICA) and Bcl-2 at 24, 48 and 72 h after the injury. The expression of spleen
      human leucocyte antigen-DR (HLA-DR) was detected by immunohistochemistry
      analysis. Selectins and adhesion molecules in lungs and serum were also detected.
      The lung injury degree was represented as wet/dry (W/D) values and alveolar
      thickness. Ulinastatin decreased MDA levels and ameliorated the down-regulation
      of SOD activity. MICA was up-regulated after the scald, and this up-regulation
      was greatly diminished by ulinastatin. Bcl-2 was up-regulated after the scald,
      especially in the U group. The spleen HLA-DR expression demonstrated the
      immunoregulatory effects of ulinastatin, which effectively protected the
      pulmonary tissues from scald-induced injury. Our results demonstrated that
      pulmonary damage was associated with autoimmunity and oxidant attack after severe
      scald. Ulinastatin exhibits significant protective effects on these effects.

PMID- 22455799
TI  - Assessment of misorientation in metallic and semiconducting nanowires using
      precession electron diffraction.
AB  - Precession electron diffraction (PED) allows for diffraction pattern collection
      under quasi-kinematical conditions. The combination of PED with fast electron
      diffraction acquisition and pattern matching software techniques is used for the
      high magnification ultra-fast mapping of variable crystal orientations and
      phases, similarly to what is achieved with the Electron Backscattered Diffraction
      technique in Scanning Electron Microscopes at lower magnifications and longer
      acquisition times. Here we report, for the first time, the application of this
      PED-based orientation mapping technique to both metallic and semiconducting
      nanowires.

PMID- 22455800
TI  - Synthesis of 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine derivatives as potent
      antimicrobial agent.
AB  - A series of 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine (7-12) have been
      synthesised by reduction of 3-alkyl-2,6-diarylpiperidin-4-one using the Grignard
      reagent. Structural assignments and conformational analysis of the compounds were
      established based on the spectral studies. All the piperdin-4-ol derivatives (7
      12) were assayed for antibacterial, antifungal and anthelmintic activities and
      they exhibited significant results.

PMID- 22455801
TI  - Cardiovascular disease risk profile and microvascular complications of diabetes:
      comparison of Indigenous cohorts with diabetes in Australia and Canada.
AB  - BACKGROUND: Indigenous populations of Australia and Canada experience
      disproportionately high rates of chronic disease. Our goal was to compare
      cardiovascular (CVD) risk profile and diabetes complications from three recent
      comprehensive studies of diabetes complications in different Indigenous
      populations in Australia and Canada. METHODS: We compared participants from three
      recent studies: remote Indigenous Australians (2002-2003, n = 37 known diabetes),
      urban Indigenous Australians (2003-2005, n = 99 known diabetes), and remote
      Aboriginal Canadians (2001-2002, n = 188 known diabetes). RESULTS: The three
      groups were similar for HbA1c, systolic BP, diabetes duration. Although leaner by
      body-mass-index criteria, remote Indigenous Australians displayed a more adverse
      CVD risk profile with respect to: waist-hip-ratio (1.03, 0.99, 0.94, remote
      Indigenous Australians, urban Indigenous Australians, remote Canadians, p <
      0.001); HDL-cholesterol (0.82, 0.96, 1.17 mmol/L, p < 0.001); urine albumin
      creatinine-ratio (10.3, 2.4, 4.5 mg/mmol); and C-reactive protein. With respect
      to diabetes complications, microalbuminuria (50%, 25%, 41%, p = 0.001) was more
      common among both remote groups than urban Indigenous Australians, but there were
      no differences for peripheral neuropathy, retinopathy or peripheral vascular
      disease. CONCLUSIONS: Although there are many similarities in diabetes phenotype
      in Indigenous populations, this comparison demonstrates that CVD risk profiles
      and diabetes complications may differ among groups. Irrespective, management and
      intervention strategies are required from a young age in Indigenous populations
      and need to be designed in consultation with communities and tailored to
      community and individual needs.

PMID- 22455802
TI  - Insights into udder health and intramammary antibiotic usage on Irish dairy farms
      during 2003-2010.
AB  - By international standards, Ireland is a relatively small dairy producer.
      However, the industry plays a critical role to the national economy, accounting
      for approximately 3% of national gross domestic product. This paper presents
      insights into udder health and intramammary antibiotic usage on Irish dairy farms
      during 2003-2010, based on data from several sources. Three data sources were
      used, including data on milk recording data, intramammary antibiotic sales and
      animal health assessment. The milk recording data included a single unadjusted
      herd-level somatic cell count (SCC) value for each herd at each milk recording,
      being the arithmetic mean of cow-level SCC of each cow at that recording,
      weighted by cow-level yield. These data were used to calculate the percentage of
      herds each month where the unadjusted herd SCC exceeded 200,000 and 400,000
      cells/mL. Two logistic generalised estimating-equations (GEE) models were
      developed, the outcome variable being either the probability that the monthly SCC
      of a herd was greater than 400,000 cells/mL or less than or equal to 200,000
      cells/mL. Spring herds had a lower probability of a high SCC (> 400,000 cells/mL)
      during February to October compared to non-Spring herds but a higher probability
      between November to January. The odds of a high SCC were greater in 2005, 2006,
      2009 and 2010 but less in 2007 and 2008 compared to 2004. Smaller herds had
      higher odds of having a high SCC compared to larger herds. We present the number
      of intramammary tubes and the quantity of active substance (kg) sold annually in
      Ireland during 2003-2010. We infer an incidence of clinical mastitis of 54.0
      cases per 100 cow-years at risk, assuming 4 tubes per treatment regime, one
      affected quarter per cow, tubes restricted to clinical cases only and 100% of
      treated cases considered new cases, based on data collected on sales of in
      lactation intra-mammary antibiotics. With differing assumptions, this estimate
      varied between 25.8 and 77.0 cases per 100 cow-years at risk. Using data on sales
      of dry cow therapy intra-mammary antibiotics, we also infer that most Irish dairy
      farmers use blanket dry cow therapy. It is important that Ireland has an
      objective understanding of current levels of udder health, to facilitate
      benchmarking and improvement into the future. Udder health is a concern on a
      number of Irish dairy farms. High SCC results were present throughout the year,
      but more marked towards the start and end of each milking season. Animal Health
      Ireland recently commenced a major national programme, CellCheck, in
      collaboration with a broad range of stakeholders, to support national SCC
      improvement. In this paper, relevant European and national legislation is also
      reviewed.

PMID- 22455803
TI  - [Upper-airway assessment for sites of airway narrowing among obstructive sleep
      apnea patients].

PMID- 22455804
TI  - [Radiation damage to the ear].

PMID- 22455805
TI  - [Relationship between obstructive sleep apnea-hypopnea syndrome and
      hypertension].
AB  - OBJECTIVE: To explore the relationship between obstructive sleep apnea-hypopnea
      syndrome (OSAHS) and hypertension. METHODS: There were 1149 middle aged patients
      who were suspected to have OSAHS underwent polysomnography (PSG) from Jan, 1999
      to June, 2011. The age of the patients ranged from 45 to 65 years. The patients
      were divided into 10 groups according to sleep apnea hypopnea index (AHI), group
      1: AHI < 5; group 2: 5 <= AHI < 15; group 3: 15 <= AHI < 30; group 4: 30 <= AHI <
      40; group 5: 40 <= AHI < 50; group 6: 50 <= AHI < 60; group 7: 60 <= AHI < 70;
      group 8: 70 <= AHI < 80; group 9: 80 <= AHI < 90; group 10: AHI >= 90. The
      incidence of hypertension in each group was tested using crosstabs method. The
      correlation between AHI, lowest oxygen saturation (LSaO2), age, body mass index
      (BMI) and hypertension were analyzed. RESULTS: Among 1149 suspected OSAHS
      patients, 1004 were diagnosed as OSAHS by PSG. There were positive correlation
      between AHI and diastolic, systolic blood pressure (r were 0.239 and 0.305,
      respectively, P < 0.01). AHI was independent risk factor of hypertension (P <
      0.001). No statistically significant difference in the incidence of hypertension
      was found among group 1 and group 2, 3, group 4 and group 5, group 6 to group 10
      (chi(2) were 3.821, 0.005 and 1.325, P > 0.05, respectively). There was
      significant difference in the incidence of hypertension among group 4 and group
      1, 2, 3, group 5 and group 6 (chi(2) were 2.615 and 4.300, P < 0.05,
      respectively). There were two cutoff points at the AHI of 30 and 50. CONCLUSION:
      With OSAHS exacerbations, the incidence of hypertension was significantly
      increased.

PMID- 22455806
TI  - [Comparation between modified coblation assisted uvulopalatopharyngoplasty and
      conventional uvulopalatopharyngoplasty in operative complication].
AB  - OBJECTIVE: To compare the operative effectivity and incidence of postoperative
      complication between conventional uvulopalatopharyngoplasty (UPPP) and modified
      coblation assisted UPPP (M-CAUP) in treating patients with obstructive sleep
      apnea-hypopnea syndrome (OSAHS). And to explore the more effective, safer and
      minimally invasive operative method in surgical therapy of OSAHS. METHODS: It was
      a controlled trial. A retrospective analysis was made on surgical complications
      of conventional UPPP and of M-CAUP performed on OSAHS patients from 1995 to 2010.
      There were 451 patients in UPPP group and 323 patients in M-CAUP group. chi(2)
      test and Fisher's Exact test were used in statistical analysis. RESULTS: The
      incidence of serious surgical complications was higher in conventional UPPP group
      (3.77%, 17/451) than that in M-CAUP group (0.62%, 2/323), chi(2) = 7.800, P <
      0.01, while the incidence of short-term complications was higher in M-CAUP group
      (90.40%, 292/323) than that in conventional UPPP group (60.98%, 275/451), chi(2)
      = 83.186, P < 0.01. The difference of long-term complications was not
      statistically significant between M-CAUP group and conventional UPPP group (P =
      0.1331, Fisher Exact test). There was no significant difference in incidence of
      asphyxia between M-CAUP group and conventional UPPP group (P < 0.01, Fisher Exact
      test). However, the incidence of post-operative primary hemorrhage was obviously
      lower in M-CAUP group than that in conventional UPPP group (3.99%, 18/451),
      chi(2) = 12.133, P < 0.01. While the incidence of delayed hemorrhage, temporal
      velopharyngeal insufficiency, and foreign body sensation at pharynx were higher
      in M-CAUP group (8.05%, 12.69%, 68.42%, respectively) than that in conventional
      UPPP group (3.77%, 3.33%, 51.00%, respectively) P < 0.01, respectively. There was
      no significant difference in incidence of permanent velopharyngeal insufficiency,
      stenosis of nasopharynx and nasopharyngeal atresia, alteration of taste, throat
      itch and coughing. CONCLUSION: Compared to the conventional UPPP, M-CAUP was more
      effective and safer in treating OSAHS with less severe complications during and
      after the operation.

PMID- 22455807
TI  - [Value of tonsillectomy in patient with obstructive sleep apnea hypopnea syndrome
      with Friedman staging I].
AB  - OBJECTIVE: To evaluate the availability of tonsillectomy in patients with
      obstructive sleep apnea hypopnea syndrome (OSAHS) staged as Friedman I. METHODS:
      Fifty-six patients with OSAHS in Friedman stage I who refused
      uvulopalatopharyngoplasty (UPPP) received tonsillectomy merely from January 2004
      to March 2010. There were 20 mild, 24 moderate and 12 serious patients
      respectively in this group. The other 68 OSAHS patients in Friedman stage I
      received UPPP at the same time as matched group, including 26 mild, 28 moderate
      and 14 serious patients. RESULTS: There was no significant difference before
      operation in terms of age, body mass index, apnea hypopnea index (AHI), the
      lowest pulse oxygen saturation (SPO(2)) and average SPO(2) between the two
      groups. There were significant difference in mean length of operation (U = 0.000,
      P < 0.01), hospitalization day (U = 458.5, P < 0.01), visual analogue scale after
      surgery (U = 0.000, P < 0.01) in these two group. There was no significant
      difference in surgical effective rate between the two groups (chi(2) = 0.857, P >
      0.05). There was also no significant difference in terms of age, body mass index,
      AHI, the lowest SPO(2) and average SPO(2) after operation between the two groups
      (t test P > 0.05). The surgical effective rate for the long term of the two
      groups was equal (chi(2) = 0.857, P > 0.05). Even patients with serious OSAHS in
      Friedman stage I, the surgical effective rate of the two groups was equivalent
      (Fisher's exact test, P > 0.05). CONCLUSIONS: Tonsillectomy is a safe and
      effective surgery for OSAHS in Friedman stage I, whose main structural load lies
      in the hypertrophic tonsil. It should be the first surgical choice for OSAHS in
      Friedman stage I.

PMID- 22455808
TI  - [Evaluation of a portable device based on peripheral arterial tone in the
      detection of obstructive sleep apnea].
AB  - OBJECTIVE: To assess the accuracy of a wrist-worn device (Watch-PAT 200) in the
      diagnosis of obstructive sleep apnea syndrome (OSAHS). METHODS: Forty-three adult
      subjects with suspected OSAHS simultaneously had a standard in-laboratory
      polysomnogram (PSG) and wore the Watch-PAT 200 during a full-night recording. PSG
      sleep and respiratory events were scored according to standard criteria. The PSG
      recordings were blindly manually analyzed, while Watch-PAT data were scored
      automatically based on the algorithm developed previously. RESULTS: The mean age
      of the subjects was (42.2 +/- 12.2) years (x(-) +/- s), and mean body mass index
      was (28.0 +/- 3.9) kg/m(2). Mean PSG apnea hypopnea index (AHI) was (34.9 +/-
      29.9) events per hour, and mean PAT-AHI was (36.0 +/- 29.2) events per hour.
      There was a significant correlation between PAT AHI and AHI by PSG (r = 0.931, P
      < 0.01). A Bland-Altman plot of PAT AHI and PSG AHI was also used to assess the
      accuracy of Watch-PAT 200. At lower levels of AHI, PAT tended to overestimate
      disease severity, while at higher levels of AHI, Watch-PAT underestimated
      severity. To assess sensitivity and specificity of Watch-PAT, constructed
      receiver operator characteristic curves using a variety of AHI threshold values
      (5, 15 and 30 events per hour). For AHI >= 5 events per hour as threshold value,
      the Watch-PAT diagnosing rate was 93%, and sensitivity as well as specificity
      were 94.7% and 80.0%. The misdiagnosis rate and missed diagnosis rate were 20.0%
      and 5.3%. Optimal combinations of sensitivity and specificity for the AHI
      threshold values (15 and 30 events per hour) were 82.6% and 100.0%, 95.0% and
      95.7% respectively. CONCLUSION: The Watch-PAT 200 may offer an accurate, robust,
      and reliable ambulatory method for the detection of OSAHS, with minimal patient
      discomfort.

PMID- 22455809
TI  - [Influence of different degrees of chronic intermittent hypoxia on c-fos protein
      and apoptosis in rats].
AB  - OBJECTIVE: To establish different degrees and duration of animal hypoxia model of
      sleep apnea hypopnea syndrome according to the mechanism of intermittent hypoxia,
      to observe the effect of c-fos protein and apoptosis, and to explore the
      mechanism of nervous system injury. METHODS: By using the model of chronic
      intermittent hypoxia in rats, male Wistar rats (n = 72) were randomly divided
      into three groups: 5% of chronic intermittent hypoxia group (the fraction of
      oxygen volume reduced to 5% under hypoxia), 10% of chronic intermittent hypoxia
      group (the fraction of oxygen volume reduced to 5% under hypoxia) and control
      group. The levels of on c-fos protein and apoptosis of hippocampal cell in three
      groups were detected at the 2nd, 4th, 6th and 8th week respectively. The
      expression of c-fos protein in hippocampal cell was detected by
      immunohistochemical method and the apoptosis of hippocampal cell was detected by
      TUNEL. RESULTS: The relative quantity of c-fos protein and apoptotic index in CIH
      groups were significantly higher than that of the control group on the 2nd, 4th,
      6th and 8th weeks (F were 44.52, 57.56, 24.20 and 13.18, P < 0.05), and these
      were higher obviously in 5% CIH group than that in 10% CIH group (P < 0.05). The
      expression of c-fos protein and apoptotic index in two CIH groups was different
      depending upon the different degree and duration of chronic intermittent hypoxia.
      With increased exposure time, the expression of c-fos protein and apoptotic index
      was high generally at first, peaked at 6th week, then down at 8th week (P <
      0.05). While it in UC group was invariability in different time (P > 0.05). The
      correlation between the relative quantity of c-fos protein and apoptotic index in
      two CIH groups was positive (r were 0.816 and 0.701, P < 0.01). CONCLUSION:
      Moderate and severe intermittent hypoxia induced the excessive expression of c
      fos protein in hippocampus, caused nerve cell apoptosis, and may play an
      important role in the mechanism of early brain injury of intermittent hypoxia.

PMID- 22455810
TI  - [Roles of spectral cues in Mandarin tone perception for sensorineural hearing
      impaired patients].
AB  - OBJECTIVE: This study aimed to evaluate the role of spectral fine structure and
      envelope information in Mandarin tone perception for sensorineural hearing
      impaired patients. METHODS: The linear predictive coding technique was applied to
      synthesize 128 tokens having spectral fine structure from one tone of a
      monosyllabic word and spectral envelope from other tones with the same syllable.
      There after, the tone response performance was assessed using these 128 speech
      materials for 20 normal-hearing and 48 sensorineural hearing-impaired patients,
      including 20 with moderate, 20 with moderate to severe, and 8 with severe hearing
      loss. RESULTS: 99.7%, 97.7%, 96.3% and 83.0% of the mean tone responses were
      consistent with spectral fine structure for the normal hearing, moderate,
      moderate to severe, and severely hearing-impaired groups, respectively. No tone
      recognition responses were observed in consistent with spectral envelope cues.
      There was a significant difference in tone recognition among the normal hearing
      group and three hearing impaired groups (chi(2) = 59.2, P < 0.001). The negative
      correlation between the averages for pure-tone hearing thresholds at frequencies
      of 500, 1000, and 2000 Hz and tone responses that were in consistent with
      spectral fine structure for the hearing-impaired subjects (r = -0.643, P <
      0.001). CONCLUSIONS: For both normal-hearing and hearing-impaired subjects,
      spectral fine structure plays an important role in tone recognition, and the
      impact of changing spectral envelope cues on tone recognition is negligible, when
      spectral fine structure cues are present. Sensorineural hearing impaired patients
      showed a progressive decrease in the recognition of lexical tones based on
      spectral fine structure cues, as their hearing loss becomes more severe.

PMID- 22455811
TI  - [Prenatal genetic test and clinical guidance for 213 hereditary deaf families].
AB  - OBJECTIVE: To summarize the workflow, strategy and experience of prenatal genetic
      test for deafness based on the 6-year clinical practice. METHODS: There were 213
      families who received prenatal test from 2005 to 2011. Among the 213 families,
      205 families had had one deaf child, including 204 couples with normal hearing
      and one couple of the deaf husband and normal wife, 8 families including 6
      couples with normal hearing and 2 deaf couples, had no child before test. Genomic
      and mitochondrial DNA of each subject was extracted from whole blood. The
      etiology and recurrent risks in 212 families were confirmed by means of the
      genetic test of GJB2, SLC26A4 and mtDNA 12sRNA, but one family carried POU3F4
      c.647G > A heterozygous mutation causing X-linked hereditary hearing impairment
      confirmed by pedigree study. The prenatal test was carried out during the
      pregnancy of all mothers from 11 to 30 weeks, and the following genetic
      information and counseling were supplied based on the results. RESULTS: The
      recurrent risk was 25% in 209 families, including 204 families with one deaf
      child and 5 families without child, among which all couples were GJB2 or SLC26A4
      mutation carriers and deaf children were caused by homozygous or compound
      GJB2/SLC26A4 mutations; The recurrent risk was 50% in 3 families, the father and
      his child in one family had compound SLC26A4 mutations and the mother with
      heterozygous SLC26A4 mutation, the wife had POU3F4 c.647G > A heterozygous
      mutation in another one family, and the husband with compound SLC26A4 mutations
      and the wife with mtDNA A1555G mutation and heterozygous SLC26A4 mutation
      simultaneously happened in the rest one family; The recurrent risk was 100% in
      one family of the deaf couple who were both found to carry homozygous or compound
      GJB2 mutations, and the deaf wife got pregnant by artificial insemination with
      the sperm from the local Human Sperm Bank. 226 times of prenatal test were
      applied in all 213 families that 11 families of them received prenatal test
      twice, and one family received three times. 46 times of prenatal testing showed
      that the fetuses carried parental mutations simultaneously or the same mutations
      with probands; while 180 times of prenatal test showed that the fetuses carried
      only one parental mutation or did not carry any mutation from parents. The
      following visit showed that all of these 180 families had given birth to babies
      who were all revealed to have normal hearing by new born hearing screening test.
      CONCLUSIONS: Prenatal diagnosis for deafness assisted by genetic test can provide
      efficient information about offspring's hearing condition, and the normative
      workflow and precise strategy highly guarantee the safe and favorable
      implementation of prenatal diagnosis.

PMID- 22455812
TI  - [Significance of acoustic rhinometry and rhinomanometry in the evaluation of
      submucous correction of nasal septum and submucous resection of inferior
      turbinate].
AB  - OBJECTIVE: To discuss the significance of acoustic rhinometry and rhinomanometry
      (RM) in the evaluation of submucous correction of nasal septum and submucous
      resection of inferior turbinate, and the correlations between the subject
      symptoms and the object results by acoustic rhinometry and RM in patients before
      and after operation. METHODS: A prospective study was conducted in forty-eight
      patients with nasal septal deviation and/or inferior turbinate hypertrophy. The
      patients were treated by submucous correction of nasal septum and/or submucous
      resection of inferior turbinate according to the patients' conditions. Visual
      analogue scale (VAS) was used to estimate the degree of nasal obstruction.
      Acoustic rhinometry and RM were used to obtain the data of nasal inspiratory
      effective resistance (IER), nasal expiratory effective resistance (EER), 0 - 5 cm
      nasal cavity volume (0 - 5 cm NCV), nasal minimal cross-sectional area (NMCA) and
      distance of the minimal cross-sectional area to the nostril (DCAN). The data were
      used to assess the airflow function of nasal cavity. Each patient was tested at
      the time both before and 4 weeks after surgery. The pre-and post operative data
      were used to calculate paired t-test by SPSS 17.0 and to disclose the Spearman
      rank correlation between VAS and IER, EER, 0 - 5 cm NCV, NMCA and DCAN
      individually. RESULTS: The preoperative data showed that VAS was (3.44 +/- 1.22),
      nasal IER was (0.66 +/- 0.27) kPa*s*L(-1), nasal EER was (0.68 +/- 0.29) kPa*s*L(
      1), 0 - 5 cm NCV was (3.98 +/- 1.30) cm(3), NMCA was (0.37 +/- 0.23) cm(2) and
      DCAN was (2.42 +/- 0.34) cm; and the postoperative data showed that VAS was (1.20
      +/- 0.80), nasal IER was (0.44 +/- 0.21) kPa*s*L(-1), nasal EER was (0.46 +/-
      0.23) kPa*s*L(-1), 0 - 5 cm NCV was (4.85 +/- 1.40) cm(3), NMCA was (0.53 +/-
      0.44) cm(2) and DCAN was (2.25 +/- 0.49) cm. Significant differences existed in
      VAS, nasal IER, EER, 0 - 5 cm NCV, NMCA and DCAN between pre-and post operative
      data (t value were 9.163, 4.995, 4.508, -4.204, -2.203, 2.924, all P < 0.05). The
      correlation coefficient between VAS and IER, EER and 0 - 5 cm NMCA was 0.386,
      0.343 and -0.307, respectively (all P < 0.05). CONCLUSION: Both acoustic
      rhinometry and RM are appropriate methods to be used in the evaluation of
      submucous correction of nasal septum and submucous resection of inferior
      turbinate, however, the correlations between the subject symptoms and the object
      results by acoustic rhinometry and RM need further research.

PMID- 22455813
TI  - [Evidence for determining the safe surgical margin for pleomorphic adenoma of
      parotid gland].
AB  - OBJECTIVE: To compare the treatment outcomes, complications and histopathologic
      features between conventional parotidectomy and functional regional parotidectomy
      in the treatment for pleomorphic adenoma of parotid gland and to provide
      clinical, and pathological evidence for determining the safe surgical margin.
      METHODS: Of 109 patients, 60 patients received conventional parotidectomy and 49
      patients received functional regional parotidectomy. The rates of tumor
      recurrence and complications were compared between the groups of patients.
      RESULTS: There was no significant difference in the incidence of tumor
      recurrence, the facial paralysis and sialosyrinx between two groups. The rates of
      Frey's syndrome, numbness of auricular region, and facial asymmetry were 30.0%,
      61.7%, and 38.3% in the patients with conventional parotidectomy respectively,
      while the rates were 6.1%, 30.6%, and 8.2% in the patients with functional
      regional parotidectomy, with significant statistically difference, respectively
      (P < 0.05). Of 109 patients, 33 with incomplete capsule, 29 with capsule
      penetration, 25 with pseudopodia, and 13 with satellite nodules. There was no
      significant difference in the depth of tumor infiltration between two groups of
      patients. For the tumor smaller than 2 cm, the depth of infiltration in
      conventional group was from 0.061 to 1.122 mm, functional group was from 0.442 to
      3.127 mm (Z = -1.093, P = 0.057); for the tumors between 2 - 4 cm, the depth in
      conventional group was from 0.081 to 7.908 mm, functional group was from 0.082 to
      6.632 mm (Z = -0.214, P = 0.831); for the tumor larger than 4 cm, the depth of
      infiltration was from 0.340 to 8.476 mm. CONCLUSIONS: Compared with conventional
      parotidectomy, functional regional parotidectomy has good outcomes and less
      complications. The surgical margins of pleomorphic adenomas of the parotid gland
      should be determined by the size of tumor. The 1 cm-surgical margins are safe for
      the tumors less than 4 cm, and the tumors more than 4 cm should be treated with
      superficial parotidectomy.

PMID- 22455814
TI  - [Resection and one-stage repair of basal cell carcinoma of external nose].
AB  - OBJECTIVE: To present the method of resection and one-stage repair of basal cell
      carcinoma of external nose. METHODS: Sixty-two patients with basal cell carcinoma
      of external nose were hospitalized and underwent surgeries from January 2002 to
      June 2010. The defects after resection were as follows: 1 partial defect of soft
      tissue of lateral ala nasi, associated defect of ala nasi margin, total defect of
      ala nasi, defect of soft tissue of apex nasi, defect of apex nasi and ala nasi,
      defect of the bridge of the nose. Various flaps were applied according to the
      degree of defects. With nasal parabolic sulci and nasolabial sulcus as the
      center, different flaps were used, including advanced skin flap, pedicle tunnel
      island flap of nasolabial sulcus, and flip flap of nasolabial sulcus, forehead
      axial flap, dissociated auricle compound soft tissue flap for one-stage repair
      respectively. RESULTS: Two flaps failed because of thanatosis after the
      surgeries. One flap mostly was a necrosis with the upper small part survived. A
      marginal partial necrosis of the flap appeared in 2 patients. Two fixing nasal
      apex and nasal wing suffered a partial circum exfoliation. All other 55 flaps
      were successfully implanted with satisfying looks and breathing functions with
      the exception of 1 complaining about obvious nasal obstruction. The rest were
      followed up for 6 months to 8 years with no relapse. CONCLUSIONS: Most of the
      tumors of external nose are basaloma, and the margin of safety should be secured
      during the operation with Mohn's surgery, and once thoroughly resected, there are
      barely relapses, and radiotherapy or chemotherapy is unnecessary. Pedicled skin
      flaps can be used as in one-stage repairing of the defect of external nose, with
      high rate of success and close color shade and good outcome.

PMID- 22455815
TI  - [Application of modified sternocleidomastoid myocutaneous flap in hypopharyngeal
      defect].
AB  - OBJECTIVE: To investigate the treatment outcomes of modified sternocleidomastoid
      myocutaneous flap with a pedicle containing superior thyroid artery in repairing
      postoperative hypopharyngeal defect. METHODS: From Dec. 2003 to Sep. 2010, the
      modified sternocleidomastoid myocutaneous flap was used to restore defect
      postoperation of hypopharynx defect for twelve patients with pyriform sinus
      carcinoma, age range from 47 to 72 years old. No patients had treated by
      radiotherapy before operation. Of 12 patients, 5 cases in T2N0M0, 5 cases in
      T3N1M0 and 2 cases in T4N1M0. RESULTS: Two cases in T4 with thyroid invasion and
      2 cases in T3 with vocal cord fixation had total laryngectomy, and the other 8
      cases were non reserved with laryngeal functions. To shape flap with middle and
      lower segment of sternocleidomastoid muscle and with superior artery as pedicle.
      All flaps survived after operation. The following-up time was 7-88 months (median
      30 months). Four patients died of recurrence or metastasis of tumor during
      following-up. CONCLUSIONS: Modified sternocleidomastoid myocutaneous flap with
      pedicle is easy to harvest, with smaller damage and a higher survival rate, which
      is a good flap for the repair of the hypopharyngeal defect after resecting
      tumour.

PMID- 22455816
TI  - [A case of spontaneous cerebrospinal fluid rhinorrhea in lateral recess of the
      sphenoid sinus].

PMID- 22455817
TI  - [Clinical analysis on adenoidectomy in infants].

PMID- 22455818
TI  - [Clinical analysis of 30 patients with severe facial and neck cut wound
      treatment].

PMID- 22455819
TI  - [Ala nasal leiomyoma misdiagnosed as nasal vestibular cyst: a case report].

PMID- 22455820
TI  - [Chondrosarcomas of sphenoid sinus and skull base: report of two cases].

PMID- 22455821
TI  - [With severe onset hypotension, bradycardia as the main performance of
      nasopharyngeal carcinoma in one case].

PMID- 22455822
TI  - [Organ resection being unjustifiable as a surgical principle].

PMID- 22455823
TI  - [The second conference briefing of the ninth editorial board of Chinese Journal
      of Otorhinolaryngology Head and Neck Surgery].

PMID- 22455824
TI  - [Summary of the 2011 national symposium on obstructive sleep apnea hypopnea
      syndrome].

PMID- 22455825
TI  - [Imaging studies of congenital anomalies of the internal auditory canal].

PMID- 22455826
TI  - [Selection and application of oral appliance on patients with obstructive sleep
      apnea hypopnea syndrome].

PMID- 22455827
TI  - [Allergic rhinoconjunctivitis].

PMID- 22455829
TI  - Journal of Women's Health. Message from the editor.

PMID- 22455828
TI  - Staying in school for lunch instead of eating in fast-food restaurants: results
      of a quasi-experimental study among high-school students.
AB  - OBJECTIVE: Following the adoption of food policies replacing unhealthy products
      by healthy foods in school, the present study tested the effectiveness of an
      intervention aimed at encouraging high-school students to stay in school for
      lunch instead of eating in fast-food restaurants. DESIGN: A 12-week multi
      strategy intervention targeting specific determinants of behaviour was evaluated
      via a quasi-experimental pre- and post-intervention design. A self-administered
      questionnaire was employed based on the theory of planned behaviour. SETTING: An
      experimental (n 129) and a control school (n 112) in central Canada. SUBJECTS:
      High-school students aged 12 to 17 years. RESULTS: Compared with control school
      students, those in the experimental school significantly increased the mean
      number of days that they stayed in school for lunch (relative risk = 1.55; 95 %
      CI 1.06, 2.27; P = 0.024), as well as the proportion who remained in school for
      lunch every day (relative risk = 1.21; 95 % CI 1.04, 1.40; P = 0.014). Among the
      psychosocial variables targeted, only self-efficacy appeared to be influenced by
      the intervention, mainly because of a decline in control group values. Mediation
      analysis indicated a significant mediating effect of self-efficacy on the mean
      number of days that students stayed in school for lunch (bias-corrected and
      accelerated point estimate = 0.079; 95 % CI 0.0059, 0.1958). CONCLUSIONS: These
      results suggest that interventions aimed at enhancing self-efficacy can
      successfully contribute to students staying in school during lunch time. Such
      interventions should be considered in obesity prevention programmes adapted to
      high-school students.

PMID- 22455830
TI  - Turkey. Health system review.
AB  - Turkey has accomplished remarkable improvements in terms of health status in the
      last three decades, particularly after the implementation of the Health
      Transformation Program (HTP (Saglikta Donus, um Programi)). Average life
      expectancy reached 71.8 for men and 76.8 for women in 2010. The infant mortality
      rate (IMR) decreased to 10.1 per 1000 live births in 2010, down from 117.5 in
      1980. Despite these achievements, there are still discrepancies in terms of
      infant mortality between rural and urban areas and different parts of the
      country, although these have been diminishing over the years. The higher infant
      mortality rates in rural areas can be attributed to low socioeconomic conditions,
      low female education levels and the prevalence of infectious diseases. The main
      causes of death are diseases of the circulatory system followed by malignant
      neoplasms. Turkeys health care system has been undergoing a far-reaching reform
      process (HTP) since 2003 and radical changes have occurred both in the provision
      and the financing of health care services. Health services are now financed
      through a social security scheme covering the majority of the population, the
      General Health Insurance Scheme (GHIS (Genel Saglik Sigortasi)), and services are
      provided both by public and private sector facilities. The Social Security
      Institution (SSI (Sosyal Guvenlik Kurumu)), financed through payments by
      employers and employees and government contributions in cases of budget deficit,
      has become a monopsonic (single buyer) power on the purchasing side of health
      care services. On the provision side, the Ministry of Health (Saglik Bakenligi)
      is the main actor and provides primary, secondary and tertiary care through its
      facilities across the country. Universities are also major providers of tertiary
      care. The private sector has increased its range over recent years, particularly
      after arrangements paved the way for private sector provision of services to the
      SSI. The most important reforms since 2003 have been improvements in citizens
      health status, the introduction of the GHIS, the instigation of a purchaser
      provider split in the health care system, the introduction of a family
      practitioner scheme nationwide, the introduction of a performance-based payment
      system in Ministry of Health hospitals, and transferring the ownership of the
      majority of public hospitals to the Ministry of Health. Future challenges for the
      Turkish health care system include, reorganizing and enforcing a referral system
      from primary to higher levels of care, improving the supply of health care staff,
      introducing and extending public hospital governance structures that aim to grant
      autonomous status to public hospitals, and further improving patient rights.

PMID- 22455831
TI  - Fabrication of ellagic acid incorporated self-assembled peptide microtubes and
      their applications.
AB  - Ellagic acid (EA), a plant polyphenol known for its wide-range of health benefits
      was encapsulated within self-assembled threonine based peptide microtubes. The
      microtubes were assembled using the synthesized precursor bolaamphiphile bis(N
      alpha-amido threonine)-1,5-pentane dicarboxylate. The self-assembly of the
      microstructures was probed at varying pH. In general, tubular formations were
      observed at a pH range of 4-6. The formed microtubes were then utilized for
      fabrication with EA. We probed the ability of the microtubes as drug release
      vehicles for EA as well as for antibacterial applications. It was found that the
      release of EA was both pH and concentration dependent. The biocompatibility as
      well as cytotoxicity of the EA-fabricated microtubes was examined in the presence
      of mammalian normal rat kidney (NRK) cells. Finally the antibacterial effects of
      the EA incorporated peptide microtubes was examined against Escherichia coli and
      Staphylococcus aureus.

PMID- 22455832
TI  - Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis
      associated major depression.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with
      a high prevalence of depression. Both MS and depression have been linked to
      elevated cortisol levels and inflammation, indicating disturbed endocrine-immune
      regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in
      the CNS has been proposed as a pathogenetic mechanism of depression.
      Intriguingly, both receptors are also expressed in lymphocytes, but their role
      for 'escape' of the immune system from endocrine control is unknown. Using
      steroid sensitivity of T cell function as a read-out system, we here investigate
      a potential role of mineralocorticoid receptor (MR) versus glucocorticoid
      receptor (GR) regulation in the immune system as a biological mechanism
      underlying MS-associated major depression. Twelve female MS patients meeting
      diagnostic criteria for current major depressive disorder (MDD) were compared to
      twelve carefully matched MS patients without depression. We performed lymphocyte
      phenotyping by flow cytometry. In addition, steroid sensitivity of T cell
      proliferation was tested using hydrocortisone as well as MR (aldosterone) and GR
      (dexamethasone) agonists. Sensitivity to hydrocortisone was decreased in T cells
      from depressed MS patients. Experiments with agonists suggested disturbed MR
      regulation, but intact GR function. Importantly, there were no differences in
      lymphocyte composition and frequency of T cell subsets, indicating that the
      differences in steroid sensitivity are unlikely to be secondary to shifts in the
      immune compartment. To our knowledge, this study provides first evidence for
      altered steroid sensitivity of T cells from MS patients with comorbid MDD
      possibly due to MR dysregulation.

PMID- 22455833
TI  - A novel application for 222Rn emanation standards: radon-cryptophane host
      chemistry.
AB  - In collaboration with the University of Pennsylvania, a (222)Rn emanation source
      was used for the determination of the binding affinity of radon to a cryptophane
      molecular host. This source was similar to a (222)Rn emanation standard that was
      developed and disseminated by the National Institute of Standards and Technology
      (NIST). The novel experimental design involved performing the reactions at
      femtomole levels, developing exacting gravimetric sampling methods and making
      precise (222)Rn assays by liquid scintillation counting. A cryptophane-radon
      association constant was determined, K(A)=(49,000+/-12,000) L mol(-1) at 293 K,
      which was the first measurement of radon binding to a molecular host.

PMID- 22455834
TI  - Association of summer temperatures with hospital admissions for renal diseases in
      New York State: a case-crossover study.
AB  - This study assessed the association between high temperatures and increased odds
      of hospitalization for renal diseases that, to date, has been examined in only a
      small number of studies. A case-crossover design was used to study 147,885
      hospital admissions with renal diagnoses during July and August, 1991-2004, in
      New York State. Regional temperature, humidity, and barometric pressure data from
      automated monitors were used as exposure indicators. By use of time-stratified
      referent selection and conditional logistic regression analysis, an overall 9%
      increase in odds of hospitalization for acute renal failure per 5 degrees F (2.78
      degrees C) was found for mean temperature at a 1-day lag (odds ratio = 1.09, 95%
      confidence interval: 1.07, 1.12). The results suggest increased susceptibility to
      hospitalization for acute renal failure for blacks, Hispanics, people aged 25-44
      years, and those in the lowest income quartile. The odds varied geographically
      with the largest associations found in the more urban regions. Increased odds of
      hospitalization were also found for urinary tract infections, renal calculi,
      lower urinary calculi, and other lower urinary tract disorders. The findings can
      help to identify vulnerable subpopulations and to inform decisions and policies
      regarding adaptation strategies and heat-warning systems.

PMID- 22455835
TI  - Does anti-obsessional pharmacotherapy treat so-called comorbid depressive and
      anxiety states?
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic condition that
      normally presents high rates of psychiatric comorbidity. Depression, tic
      disorders and other anxiety disorders are among the most common comorbidities in
      OCD adult patients. There is evidence that the higher the number of psychiatric
      comorbidities, the worse the OCD treatment response. However, little is known
      about the impact of OCD treatment on the outcome of the psychiatric comorbidities
      usually present in OCD patients. The aim of this study was to investigate the
      impact of exclusive, conventional treatments for OCD on the outcome of additional
      psychiatric disorders of OCD patients, detected at baseline. METHODS: Seventy-six
      patients with primary OCD admitted to the treatment protocols of the Obsessive
      Compulsive Spectrum Disorders Program between July 2007 and December 2009 were
      evaluated at pre-treatment and after 12 months. Data were analyzed to verify
      possible associations between OCD treatment response and the outcome of
      psychiatric comorbidities. RESULTS: Results showed a significant association
      between OCD treatment response and improvement of major depression and dysthymia
      (p-value=0.002), other anxiety disorders (generalized anxiety disorder, social
      phobia, specific phobia, posttraumatic stress disorder, panic disorder,
      agoraphobia and anxiety disorder not otherwise specified) (p-value=0.054) and tic
      disorders (p-value=0.043). LIMITATIONS: This is an open, non-blinded study,
      without rating scales for comorbid conditions. Further research is necessary
      focusing on the possible mechanisms by which OCD treatment could improve these
      specific disorders. CONCLUSIONS: Our results suggest that certain comorbid
      disorders may benefit from OCD-targeted treatment.

PMID- 22455836
TI  - Engineering Escherichia coli for succinate production from hemicellulose via
      consolidated bioprocessing.
AB  - BACKGROUND: The recalcitrant nature of hemicellulosic materials and the high cost
      in depolymerization are the primary obstacles preventing the use of xylan as
      feedstock for fuel and chemical production. Consolidated bioprocessing,
      incorporating enzyme-generating, biomass-degrading and bioproduct-producing
      capabilities into a single microorganism, could potentially avoid the cost of the
      dedicated enzyme generation in the process of xylan utilization. In this study,
      we engineered Escherichia coli strains capable of exporting three hemicellulases
      to the broth for the succinate production directly from beechwood xylan. RESULTS:
      Xylanases were extracellular environment-directed by fusing with OsmY.
      Subsequently, twelve variant OsmY fused endoxylanase-xylosidase combinations were
      characterized and tested. The combination of XynC-A from Fibrobacter succinogenes
      S85 and XyloA from Fusarium graminearum which appeared to have optimal enzymatic
      properties was identified as the best choice for xylan hydrolysis (0.18 +/- 0.01
      g/l protein in the broth with endoxylanase activity of 12.14 +/- 0.34 U/mg
      protein and xylosidase activity of 92 +/- 3 mU/mg protein at 8 h after
      induction). Further improvements of hemicellulases secretion were investigated by
      lpp deletion, dsbA overexpression and expression level optimization. With co
      expression of alpha-arabinofuranosidase, the engineered E. coli could hydrolyze
      beechwood xylan to pentose monosaccharides. The hemicellulolytic capacity was
      further integrated with a succinate-producing strain to demonstrate the
      production of succinate directly from xylan without externally supplied
      hydrolases and any other organic nutrient. The resulting E. coli Z6373 was able
      to produce 0.37 g/g succinate from xylan anaerobically equivalent to 76% of that
      from xylan acid hydrolysates. CONCLUSIONS: This report represents a promising
      step towards the goal of hemicellulosic chemical production. This engineered E.
      coli expressing and secreting three hemicellulases demonstrated a considerable
      succinate production on the released monosaccharides from xylan. The ability to
      use lower-cost crude feedstock will make biological succinate production more
      economically attractive.

PMID- 22455837
TI  - Bioconversion of glycerol to ethanol by a mutant Enterobacter aerogenes.
AB  - The main objective of this research is to develop, by adaptive evolution, mutant
      strains of Enterobacter aerogenes ATCC 13048 that are capable of withstanding
      high glycerol concentration as well as resisting ethanol-inhibition. The mutant
      will be used for high ethanol fermentation from glycerol feedstock. Ethanol
      production from pure (P-) and recovered (R-) glycerol using the stock was
      evaluated. A six-tube-subculture-generations method was used for developing the
      mutant. This involved subculturing the organism six consecutive times in tubes
      containing the same glycerol and ethanol concentrations at the same culture
      conditions. Then, the glycerol and/or ethanol concentration was increased and the
      six subculture generations were repeated. A strain capable of growing in 200 g/L
      glycerol and 30 g/L ethanol was obtained. The ability of this mutant, vis-a-vis
      the original strain, in utilizing glycerol in a high glycerol containing medium,
      with the concomitant ethanol yield, was assessed. Tryptic soy broth without
      dextrose (TSB) was used as the fermentation medium. Fermentation products were
      analyzed using HPLC.In a 20 g/L glycerol TSB, E. aerogenes ATCC 13048 converted
      18.5 g/L P-glycerol and 17.8 g/L R-glycerol into 12 and 12.8 g/L ethanol,
      respectively. In a 50 g/L P-glycerol TSB, it utilized only 15.6 g/L glycerol; but
      the new strain used up 39 g/L, yielding 20 g/L ethanol after 120 h, an
      equivalence of 1.02 mol ethanol/mol-glycerol. This is the highest ethanol yield
      reported from glycerol bioconversion. The result of this P-glycerol fermentation
      can be duplicated using the R-glycerol from biodiesel production.

PMID- 22455838
TI  - Chemical composition and in vitro antimicrobial activity of the essential oil of
      Cyclotrichium leucotrichum from Iran.
AB  - The objective of this study was to investigate in vitro antimicrobial activity
      and composition of the essential oil of Cyclotrichium leucotrichum growing wild
      in Iran. The essential oil was obtained by hydro-distillation and analysed by GC
      FID and GC/MS. Fifty-nine components representing 98.9% of the total oil were
      characterised. The essential oil which has 1,8-cineol (14.8%), elemol (12.6%),
      spathulenol (9.4%), E-caryophyllene (5.7%) and hinesol (5.7%) as its main
      components, exhibited moderate activity against seven bacteria and a yeast,
      Candida albicans, with minimum inhibitory concentration values ranging from 0.5
      to 64 mg mL(-1) and minimum bactericidal concentration values ranging from 2 to
      >64 mg mL(-1), respectively. The best inhibitory effects were against three gram
      positive bacteria and tested yeast, C. albicans.

PMID- 22455840
TI  - The role of the frontal eye fields in oculomotor competition: image-guided TMS
      enhances contralateral target selection.
AB  - In order to execute a correct eye movement to a target in a search display, a
      saccade program toward the target element must be activated, while saccade
      programs toward distracting elements must be inhibited. The aim of the present
      study was to elucidate the role of the frontal eye fields (FEFs) in oculomotor
      competition. Functional magnetic resonance imaging-guided single-pulse
      transcranial magnetic stimulation (TMS) was administered over either the left
      FEF, the right FEF, or the vertex (control site) at 3 time intervals after target
      presentation, while subjects performed an oculomotor capture task. When TMS was
      applied over the FEF contralateral to the visual field where a target was
      presented, there was less interference of an ipsilateral distractor compared with
      FEF stimulation ipsilateral to the target's visual field or TMS over vertex.
      Furthermore, TMS over the FEFs decreased latencies of saccades to the
      contralateral visual field, irrespective of whether the saccade was directed to
      the target or to the distractor. These findings show that single-pulse TMS over
      the FEFs enhances the selection of a target in the contralateral visual field and
      decreases saccade latencies to the contralateral visual field.

PMID- 22455841
TI  - [Development and validation of a nutritional knowledge questionnaire among 9- to
      15-year-olds].
AB  - Improving nutritional knowledge is a frequent goal in nutritional education
      programs. However, there is a lack of valid instruments to assess nutritional
      knowledge in children. Questionnaires on nutritional knowledge are usually
      related to a specific curriculum or program, and their development or validation
      process is rarely available. Our goal was to develop a valid, self-administered
      questionnaire to assess nutritional knowledge among French-speaking children and
      adolescents aged 9-15 years. The conceptual framework and concepts were based on
      a literature review. For each concept, an expert panel selected a number of
      items, and successive versions of the questionnaire were pretested. The edited
      version of a 30-item questionnaire (QuesCA) was administered to 475 children aged
      9-15, in two French-speaking cantons in Switzerland. We calculated internal
      consistency (Cronbach alpha), the rate of correct answers for each question, and
      the mean scores for each concept. The mean scores were 16.32 (95% CI: [15.69;
      16.94]) in the 9- to11-year-olds and 18.62 [18.19; 19.06] in the 12- to 15-year
      olds (maximum possible, 30). Beverages, breakfast, fruit, and vegetables were the
      concepts that gathered the most correct answers. The overall Cronbach alpha score
      was good (0.66), but as the internal consistency for each concept was low (0.06
      0.45), we developed an optimal scale for each age group. The result is a two-part
      questionnaire: QuesCA 9-11 and QuesCA 12-15, with 9 items each, that enables a
      rapid and reliable assessment of nutritional knowledge in children and
      adolescents.

PMID- 22455839
TI  - Bilateral subcortical heterotopia with partial callosal agenesis in a mouse
      mutant.
AB  - Cognition and behavior depend on the precise placement and interconnection of
      complex ensembles of neurons in cerebral cortex. Mutations that disrupt migration
      of immature neurons from the ventricular zone to the cortical plate have provided
      major insight into mechanisms of brain development and disease. We have
      discovered a new and highly penetrant spontaneous mutation that leads to large
      nodular bilateral subcortical heterotopias with partial callosal agenesis. The
      mutant phenotype was first detected in a colony of fully inbred BXD29 mice
      already known to harbor a mutation in Tlr4. Neurons confined to the heterotopias
      are mainly born in midgestation to late gestation and would normally have
      migrated into layers 2-4 of overlying neocortex. Callosal cross-sectional area
      and fiber number are reduced up to 50% compared with coisogenic wildtype BXD29
      substrain controls. Mutants have a pronounced and highly selective defect in
      rapid auditory processing. The segregation pattern of the mutant phenotype is
      most consistent with a two-locus autosomal recessive model, and selective
      genotyping definitively rules out the Tlr4 mutation as a cause. The discovery of
      a novel mutation with strong pleiotropic anatomical and behavioral effects
      provides an important new resource for dissecting molecular mechanisms and
      functional consequences of errors of neuronal migration.

PMID- 22455842
TI  - [Application of PCR combined with reverse line blot assay in detection and
      identification of common pathogenic Aspergillus in fungal sinusitis].
AB  - OBJECTIVE: To evaluate the feasibility of PCR/reverse line blot hybridization
      (RLB) assay in the detection and identification of clinical pathogens in fungal
      sinusitis (FS). METHODS: Twenty-six formalin-fixed and paraffin-embedded tissues
      and 8 fresh tissues of FS were collected from Beijing Tongren Hospital, Capital
      Medical University from May 2009 to February 2010. Pathological examination,
      fungal culture and ITS2 region sequencing were carried out. The DNA of all
      samples was extracted by standard procedure and fungal universal primers ITS3 and
      ITS4 were used for PCR amplification of all tissues. Then the amplified products
      were used for RLB with five fungal species-specific probes. The results of
      PCR/RLB were compared with ITS region sequencing, fungal culture and pathological
      examination. RESULTS: For the biopsy tissues, fungal cultures were positive in 14
      cases (41.2%); pathologic examination demonstrated fungal hyphae in all cases;
      ITS2 region sequencing was successful in 16 cases (47.1%); PCR/RLB showed A.
      flavus in 14 cases, A. fumigatus in 10 cases, A. niger in four cases, A. nidulans
      in one case, A. flavus and A. fumigatus in three cases, and A. fumigatus and A.
      niger in two cases. CONCLUSIONS: The PCR/RLB assay is suitable for rapid and
      accurate detection and identification of the pathogenic fungus of FS. Compared
      with the conventional fungal culture and microscopy, pathologic examination and
      DNA sequencing, the PCR/RLB has the advantages of more economy, time saving, and
      higher sensitivity, specificity and throughput.

PMID- 22455843
TI  - [Extranodal Rosai-Dorfman disease of upper respiratory tract: a clinicopathologic
      study].
AB  - OBJECTIVE: To study the clinicopathologic features and differential diagnosis of
      extranodal Rosai-Dorfman disease (RDD) of the upper respiratory tract. METHODS:
      The clinical, pathologic and immunohistochemical features of 10 cases of RDD were
      evaluated. RESULTS: Among the 10 cases studied, there were 3 males and 7 females.
      The age of patients ranged from 20 to 61 years old (mean 38 years). The lesion
      arose in the nasal cavity (7 cases), nasopharynx (2 cases) or hard palate to
      trachea (1 case). Most of the patients presented with nasal obstruction,
      rhinorrhagia or tumor mass in the nasal/nasopharyngeal regions. CT scan often
      showed the presence of soft tissue lesion without bone destruction.
      Histologically, extranodal RDD was characterized by light-staining bands
      alternating with dark-staining bands. The light-staining bands were formed by
      aggregates of large round or polygonal histiocytes with emperipoiesis. The dark
      staining bands were formed by abundant lymphoplasmacytic infiltrates.
      Immunohistochemical study showed that the histiocytes strongly expressed S-100
      protein and partially expressed CD68. Six patients had no recurrence after
      surgical resection. CONCLUSIONS: Extranodal RDD of the upper respiratory tract is
      a rare disorder of histiocytic proliferation, which usually involves the nasal
      cavity and paranasal sinuses. RDD can easily mimic rhinoscleroma, mainly due to
      the overlapping morphologic appearance. Immunohistochemical study is helpful in
      the differential diagnosis.

PMID- 22455844
TI  - [Pulmonary capillary hemangiomatosis: a clinicopathologic analysis of 2 cases
      with review of literature].
AB  - OBJECTIVE: To investigate the clinicopathologic features of pulmonary capillary
      hemangiomatosis (PCH). METHODS: The clinical and pathologic profiles of 2 PCH
      cases were evaluated. Immunohistochemical study (EnVision method) was performed
      on fixed tissues. The biologic behavior was analyzed with follow-up data.
      RESULTS: The main presenting symptom was dyspnea. Chest radiography of the two
      cases depicted diffuse, ground-glass nodules, accompanied by enlarged central
      pulmonary arteries. Microscopically, the most distinctive feature was
      proliferation of capillary channels within pulmonary interstitium and alveolar
      walls, accompanied by muscularization of arterioles. Immunohistochemical study
      showed an abundance of mast cells in the lesion, and staining for platelet
      derived growth factor receptor-beta (PDGFR-beta) localized to vascular smooth
      muscles surrounding the proliferating capillaries and the mast cells. The index
      of Ki-67 was less than 1 percent and the p53 was negative. CONCLUSIONS: PCH is a
      rare vascular proliferative disease of yang patients. Increased number of mast
      cell and the up-regulation of PDGFR-beta may suggest mechanism for PCH. The
      clinical and radiologic diagnosis of PCH can be very difficult, and the
      histological examination is regarded as the most reliable means to establish the
      diagnosis. Pathologists should improve their knowledge on PCH.

PMID- 22455845
TI  - [Detection of epidermal growth factor receptor gene mutation in non-small cell
      lung cancer by allele-specific oligonucleotide-PCR and bi-loop probe specific
      primer quantitative PCR].
AB  - OBJECTIVE: To compare the detection sensitivity of epidermal growth factor
      receptor (EGFR) mutations between allele specific oligonucleotide PCR (ASO-PCR)
      and bi-loop probe and specific primer quantitative PCR (BPSP-qPCR). METHODS: A
      total of 96 non-small cell lung cancer specimens were selected from West China
      Hospital from September 2009 to December 2010. ASO-PCR was developed to detect
      the presence of classical EGFR mutations. A total 39 available specimens were
      also tested by BPSP-qPCR. RESULTS: EGFR mutation detection rate was 30.2% (26/96)
      by ASO-PCR. The mutation rate was higher in female than in male patients [45.5%
      (20/44) vs. 17.3% (9/52), P = 0.003], non-smokers than smokers [44.1% (26/59) vs.
      8.1% (3/37), P < 0.001] and adenocarcinomas than other subtypes of lung cancer
      [37.0% (27/73) vs. 8.7% (2/23), P = 0.01]. Among mutation negative cases by ASO
      PCR, BPSP-qPCR increased the rate of detection of 19-del and L858R mutation by
      10.3% (4/39) in adenocarcinomas and non-smoking subset. Overall, the mutation
      detection rate of BPSP-qPCR was higher than that of ASO-PCR [66.7% (26/39) vs.
      41.0% (16/39), P = 0.02]. CONCLUSION: BPSP-qPCR has a better detection
      sensitivity than that of ASO-PCR.

PMID- 22455846
TI  - [Expression and significance of neurogenic differentiation protein in pancreatic
      carcinoma].
AB  - OBJECTIVE: To investigate the expression and significance of neurogenic
      differentiation protein (NeuroD) in pancreatic carcinoma. METHODS: The expression
      of NeuroD, PCNA and p53 proteins in 127 specimens of pancreatic carcinoma was
      detected by tissue microarray and immunohistochemestry. The correlations were
      analyzed between NeuroD and PCNA, p53, neural invasion, sleeve-like lymphocytic
      infiltration around the nerve, pancreatitis adjacent to carcinoma, lymph node
      metastasis and age, gender, location of tumors, histological types and
      differentiation of pancreatic carcinomas. RESULTS: The positive rates of NeuroD,
      PCNA and p53 expression were higher in pancreatic carcinoma than those in non
      tumor pancreatic tissues [64.6% (82/127) vs 10.5% (8/76), 57.5% (73/127) vs 9.2%
      (7/76), 59.1% (75/127) vs 9.2% (7/76), P < 0.01]. NeuroD expression in pancreatic
      carcinoma was related to that of PCNA and p53 and neural invasion (P < 0.05). No
      significant correlation was found between NeuroD and age, gender, tumor location,
      histological types and differentiation, sleeve-like lymphocytic infiltration,
      pancreatitis adjacent to the carcinoma and lymph node metastasis in pancreatic
      carcinomas. CONCLUSIONS: NeuroD overexpression in pancreatic carcinoma. The
      overexpression of NeuroD may contribute to the tumorogenesis and development of
      pancreatic carcinoma, and is closely correlated to the cancer cell proliferation,
      p53 signal pathway and neural invasion in pancreatic carcinoma.

PMID- 22455847
TI  - [Expression and clinical significance of miR-23a and metastasis suppressor 1 in
      colon carcinoma].
AB  - OBJECTIVE: To investigate the expression of miR-23a and metastasis suppressor 1
      (MTSS1) and their clinical significance in colon carcinoma. METHODS: A total of
      92 cases of colon carcinomas were collected with both the tumor and paired normal
      tissue samples for the study. The miR-23a targeting MTSS1 was evaluated by
      luciferase reporter vector. Cell invasion potential was evaluated by trans-well
      invasion assay. In-situ hybridization and immunohistochemistry were used to
      detect miR-23a and MTSS1 expression. RESULTS: MiR-23a downregulated the
      expression of MTSS protein and enhanced the invasiveness of colon carcinoma. The
      expression rates of miR-23a and MTSS1 were 87.0% (80/92) and 17.4% (16/92) in
      colon carcinoma cases, respectively (P < 0.01). The up-regulation of miR-23a
      expression was associated with an advanced clinical stage (P = 0.029) and depth
      of invasion (P = 0.000). The expression of miR-23a was higher in the tumors with
      lymph node metastasis than those without (P = 0.041). Down-regulation of MTSS1
      expression was associated with an advanced clinical stage (P = 0.027) and depth
      of invasion (P = 0.017). The expression of MTSS1 was lower in the tumors with
      lymph node metastasis than those without (P = 0.009). The expression of miR-23a
      had significantly negative correlation with that of MTSS1 (r = -0.594, P =
      0.013). CONCLUSIONS: MiR-23a expression promotes colon carcinoma cell growth,
      invasion and metastasis through inhibition of MTSS gene. Both the low expression
      of MTSS1 and high expression of miR-23a may serve as important biological markers
      for the malignant phenotypes of colon cancer, such as invasion and metastasis.

PMID- 22455848
TI  - [Expression and promotor methylation of p73 gene in ovarian epithelial tumors].
AB  - OBJECTIVE: To investigate the expression and promoter methylation status of p73
      gene in ovarian epithelial tumors and their clinicopathological correlations.
      METHODS: Tissue microarrays (TMA) consisting of 68 ovarian cancers, 37 ovarian
      borderline tumors and 21 ovarian benign tumors were constructed. p73 expression
      was detected by immunohistochemistry (EnVision method). Fresh-frozen tissue
      samples from 13 cases of ovarian carcinomas and 5 cases of borderline tumors were
      evaluated for the presence of p73 promoter methylation using bisulfite
      sequencing. RESULTS: Overall, 92.6% (63/68) ovarian carcinomas expressed p73,
      with a mean value of 32% (percentage of p73 positive cells in the tumor). The
      mean value of p73 expression rate (40%) in serous carcinoma (26/26) was higher
      than those of other cancer types (P = 0.006). The mean value of p73 expression
      rate (40%) in type II ovarian carcinoma was significantly higher than that in
      type I ovarian carcinoma (24%, P = 0.010). The expression of p73 was not
      associated with FIGO stage and histological grade (both P > 0.05). The mean
      values of p73 expression in ovarian borderline tumor (30/37) and benign tumor
      (12/21) were 16% and 15%, respectively. Of the two groups, the mean value of p73
      expression rate in serous type was higher than that in mucous type (P = 0.003, P
      = 0.026). Ovarian carcinomas had a higher level of p73 expression than borderline
      tumors and benign tumors (both P < 0.05), while that between ovarian borderline
      tumors and benign tumors had no statistical difference (P > 0.05). Among serous
      tumors (49/53), the mean value of p73 expression in the carcinoma group (26/26)
      was significantly higher than those in the borderline tumor group (12/14) and
      benign tumor group (11/13; P = 0.024 and P = 0.002, respectively), while that
      between borderline tumor group and benign tumor group had no statistical
      difference (P = 0.428). Among mucous tumors (15/27), the mean value of p73
      expression in carcinoma group (6/7) was higher than that in benign tumor group
      (1/8; P = 0.032). No statistical difference of p73 expression was seen between
      the carcinoma group and ovarian borderline tumor group (8/12) and between the
      borderline tumor group and benign tumor group (P = 0.234, P = 0.201,
      respectively). p73 promotor methylation was found in 8 of 13 cases of carcinomas
      but at different methylation levels with a mean value of 8.0%. Two of 5 ovarian
      borderline tumors showed detectable p73 promotor methylation with a mean value of
      9.0%. Compared with the borderline tumors, ovarian carcinomas showed a similar
      p73 methylation level (P > 0.05). The p73 methylation level in ovarian carcinomas
      was not associated with histological type, pathogenetic type, histological grade
      and FIGO stage (all P > 0.05). CONCLUSIONS: Most of ovarian epithelial tumors
      express p73 protein with mean values higher in ovarian carcinomas than those in
      the borderline and benign tumors. Ovarian serous carcinomas have the highest
      expression level of p73. A simple linear correlation does not exist between the
      promoter methylation and protein expression of p73.

PMID- 22455849
TI  - [Primary intermediate hemangioendothelioma of bone: a study of 5 cases].
AB  - OBJECTIVE: To study the radiologic and pathologic features of primary
      intermediate hemangioendothelioma of the bone. METHODS: Five cases of primary
      intermediate hemangioendothelioma of bone encountered in the past three years
      were enrolled into the study. The clinical, radiologic, pathologic and
      immunohistochemical features of the tumors were reviewed. RESULTS: The patients
      included 3 children with Kaposiform hemangioendothelioma and 2 elderly with
      retiform hemangioendothelioma. Four of the cases affected long bones and the
      remaining case affected the clavicle. One case showed multifocal involvement of
      the humerus. Radiologically, the tumors showed borderline to low-grade bony
      destruction, with various degrees of cortical defect. Intralesional or
      perilesional bone formation was demonstrated in 4 cases and radial spicules were
      seen in 1 case. The histopathologic features of primary intermediate
      hemangioendothelioma of bone were similar to those of soft tissue, except for the
      presence of reactive bone formation. Immunohistochemically, the tumor cells were
      positive for CD31 (5/5), CD34 (5/5), vimentin (5/5) and smooth muscle actin (3/5)
      but negative for cytokeratin and epithelial membrane antigen. CONCLUSIONS:
      Primary intermediate hemangioendothelioma of bone is a distinct entity and
      similar histologic classification applies as in its soft tissue counterparts.
      Comparison of the biologic behavior requires long-term follow-up studies.

PMID- 22455850
TI  - [Value of cytopathology in endobronchial ultrasound-guided transbronchial needle
      aspiration].
AB  - OBJECTIVE: To evaluate the role of cytopathology in endobronchial ultrasound
      guided transbronchial needle aspiration (EBUS-TBNA) for lung tumor diagnosis and
      staging. METHODS: Two-hundred consecutive cases of lung tumor with EBUS-TBNA
      performed during the period from April, 2009 to September, 2010 in Shanghai
      Cancer Hospital were retrospectively reviewed. The cytologic diagnoses were
      categorized as non-diagnostic, negative, suspicious and malignant. When
      available, cell block preparation and immunohistochemistry were performed. On the
      22 positive cases diagnosed by on-site evaluation, epidermal growth factor
      receptor (EGFR) mutation study was carried out. RESULTS: In the 200 cases of
      cytology specimens, 122 cases (69.3%) were diagnosed as malignant, 42 cases
      (23.9%) as benign and 12 cases (6.8%) as suspicious for malignancy. The non
      diagnostic rate was 12.0% (24/200). Amongst the 200 cases studied, 140 cases
      (70.0%) had histologic correlation available (via core biopsy, mediastinoscopic
      biopsy or surgical excision). The sensitivity and specificity of EBUS-TBNA
      cytologic diagnoses were 94.4% and 100%, when using histopathologic findings and
      clinical follow-up data as gold standard. The cell block preparation and
      immunohistochemistry were useful in subtyping and diagnosis of extrathoracic
      malignancy. EGFR mutations were detected in 8 cytology samples (36.4%).
      CONCLUSIONS: EBUS-TBNA is a sensitive and specific tool for diagnosis and staging
      of lung cancer. The cytology samples can be used for further ancillary
      investigations including cell block preparation, immunohistochemistry and
      molecular studies.

PMID- 22455851
TI  - [Safety issues related to fine needle aspiration cytology of thyroid nodules].

PMID- 22455852
TI  - [Lipidized fibrous histiocytoma: report of a case].

PMID- 22455853
TI  - [Inclusion body fibromatosis: report of a case].

PMID- 22455854
TI  - [Primary pulmonary invasive carcinoma ex pleomorphic adenoma: report of a case].

PMID- 22455855
TI  - [Duodenal gangliocytic paraganglioma: report of a case].

PMID- 22455856
TI  - [Clinical manifestation of lymphoma and its significance in pathological
      diagnosis].

PMID- 22455857
TI  - [Progress of targeted therapy related to K-ras mutation].

PMID- 22455858
TI  - [Mutant K-ras gene in pathogenesis of pancreatic ductal adenocarcinoma].

PMID- 22455859
TI  - Association of comorbid anxiety with social functioning in school-age children
      with and without attention-deficit/hyperactivity disorder (ADHD).
AB  - Although attention-deficit/hyperactivity disorder (ADHD) is frequently comorbid
      with disruptive behavior disorders, less is known about ADHD and comorbid
      anxiety. To improve understanding about the association of anxiety and social
      functioning, we studied 223 6 to 9 year-old ethnically diverse boys and girls
      (M=7.4 years) with and without ADHD. According to parents, children with ADHD and
      anxiety (n=46) and ADHD only (n=71) were consistently less socially competent
      than comparison children (i.e., no anxiety and ADHD: n=80) and children with
      anxiety only (n=26), who did not differ from one another. A similar pattern
      emerged for teacher ratings where youth with ADHD only and ADHD with anxiety
      exhibited the most social problems, but they did not differ from each other.
      These data suggest that comorbid anxiety does not exacerbate social dysfunction
      among 6 to 9 year-old children with ADHD. We consider findings within a
      developmental psychopathology framework to further understand social development
      in children with ADHD and anxiety.

PMID- 22455860
TI  - "Living from day to day": food insecurity, complexity, and coping in muTare,
      Zimbabwe.
AB  - In Zimbabwe, unpredictable conditions associated with structural and
      institutional factors exacerbated the combined effects of structural violence,
      economic and political instability, and climate change in the mid 2000s,
      contributing to widespread food insecurity. Drought, food shortages, and
      government settlement policy affecting both rural and urban populations has
      yielded a national human rights crisis. Drawing on ethnographic research
      conducted in Mutare, southeast Zimbabwe, in 2005-2006, the authors illustrate the
      flow-on effects of drought and government policy on the livelihoods of households
      already suffering as a result of the social impacts of AIDS, and how people in a
      regional city responded to these factors, defining and meeting their basic food
      needs in diverse ways.

PMID- 22455861
TI  - Impact of sodium arsenite on certain biomolecules of nutritional importance on
      the edible components of the economically important catfish C. batrachus (Linn.).
AB  - The toxicity of sublethal concentration (1 mg/L; 5% of 96hLC(50) value) of sodium
      arsenite (NaAsO(2)) for 60 days on certain biomolecules (proteins, lipids, and
      water) of five vital organ systems (muscles, liver, brain, skin, and gills) of
      Clarias batrachus were analyzed to evaluate the damage rendered to the food value
      of the fish. Arsenic disturbs the equilibrium existing between these
      nutritionally important macromolecules in all the organ systems. These tissues
      showed marked fluctuations in their protein (1.56 +/- 0.79% in gills to 4.46 +/-
      1.54% in muscles), lipid (1.79 +/- 0.89% in skins to 4.81 +/- 1.15% in brain
      tissue) and water contents (65.84 +/- 1.01% in brain to 78.66 +/- 0.37% in
      gills).

PMID- 22455862
TI  - Chestnuts and spring chickens: conflict and change in farmers market ideologies.
AB  - The taxonomy of farmers markets requires an update to encompass the expanding
      range of available options. Also absent from the literature is an appreciation of
      the connection between market types, ideological stances, social characteristics,
      and conflict-necessary for understanding the social processes, motivations, and
      expectations that create a farmers market. Our study of a long-standing farmers
      market on the verge of municipal revamping aims to unite these interests, with a
      focus on the diverse demographics and values of the social groups involved. We
      propose a synthetic two-dimensional scheme to classify U.S. farmers markets.
      Bourdieu's theory of distinction is instrumental in making sense of the diversity
      encountered.

PMID- 22455863
TI  - HIV and severity of seasonal household food-related coping behaviors in rural
      Ghana.
AB  - In-depth research was conducted to evaluate the seasonal food insecurity of HIV
      positive and HIV-negative farm households in the Eastern Region, Ghana. A Coping
      Strategy Index (CSI) was used to assess household food-related coping behaviors.
      HIV-positive farm households often relied on both less severe and more severe
      coping behaviors, had a higher CSI, cultivated a smaller field area, harvested
      fewer food species from farms and gardens, and obtained income from fewer sources
      than HIV-negative farm households in both the post-harvest and lean seasons. We
      conclude that food insecurity is more severe in HIV-positive than in HIV-negative
      farm households in both seasons.

PMID- 22455864
TI  - Estimates of child deaths prevented from malaria prevention scale-up in Africa
      2001-2010.
AB  - BACKGROUND: Funding from external agencies for malaria control in Africa has
      increased dramatically over the past decade resulting in substantial increases in
      population coverage by effective malaria prevention interventions. This
      unprecedented effort to scale-up malaria interventions is likely improving child
      survival and will likely contribute to meeting Millennium Development Goal (MDG)
      4 to reduce the < 5 mortality rate by two thirds between 1990 and 2015. METHODS:
      The Lives Saved Tool (LiST) model was used to quantify the likely impact that
      malaria prevention intervention scale-up has had on malaria mortality over the
      past decade (2001-2010) across 43 malaria endemic countries in sub-Saharan
      African. The likely impact of ITNs and malaria prevention interventions in
      pregnancy (intermittent preventive treatment [IPTp] and ITNs used during
      pregnancy) over this period was assessed. RESULTS: The LiST model conservatively
      estimates that malaria prevention intervention scale-up over the past decade has
      prevented 842,800 (uncertainty: 562,800-1,364,645) child deaths due to malaria
      across 43 malaria-endemic countries in Africa, compared to a baseline of the year
      2000. Over the entire decade, this represents an 8.2% decrease in the number of
      malaria-caused child deaths that would have occurred over this period had malaria
      prevention coverage remained unchanged since 2000. The biggest impact occurred in
      2010 with a 24.4% decrease in malaria-caused child deaths compared to what would
      have happened had malaria prevention interventions not been scaled-up beyond 2000
      coverage levels. ITNs accounted for 99% of the lives saved. CONCLUSIONS: The
      results suggest that funding for malaria prevention in Africa over the past
      decade has had a substantial impact on decreasing child deaths due to malaria.
      Rapidly achieving and then maintaining universal coverage of these interventions
      should be an urgent priority for malaria control programmes in the future.
      Successful scale-up in many African countries will likely contribute
      substantially to meeting MDG 4, as well as succeed in meeting MDG 6 (Target 1) to
      halt and reverse malaria incidence by 2015.

PMID- 22455865
TI  - Cyclooxygenase inhibitory properties of nor-neolignans from Styrax pohlii.
AB  - Chemical investigation of the n-hexane and EtOAc fractions of the ethanolic
      extract from Styrax pohlii (Styracaceae) aerial parts resulted in the isolation
      of the benzofuran nor-neolignan derivatives egonol (1), homoegonol (2),
      homoegonol gentiobioside (3), homoegonol glucoside (4) and egonol gentiobioside
      (5). This is the first report of compounds 1-5 in S. pohlii. Compounds 1-5, the
      acetyl derivatives 1 a and 2 a, the ethanolic extract (EE), the n-hexane fraction
      (HF) and EtOAc fraction (EF) were tested for their inhibitory activities against
      COX-1 and COX-2. The results showed that EE, HF, EF and compounds 1-5 and 1 a-2 a
      shown weak to moderate inhibition of COX-1 and COX-2. Among the assayed nor
      neolignans, 4 gave a COX-1 inhibition of 35.7% at 30 uM. Compound 5 displayed a
      COX-2 inhibition of 19.7% at 30 uM.

PMID- 22455866
TI  - The efficacy of renal angioplasty in patients with renal artery stenosis and
      flash oedema or congestive heart failure: a systematic review.
AB  - AIMS: Recent randomized controlled trials have reported that angioplasty does not
      have a beneficial effect compared with pharmacological treatment on blood
      pressure and renal function in patients with atherosclerotic renal artery
      stenosis (RAS). We aimed to explore systematically the evidence that angioplasty
      is effective in subgroups of patients with RAS and either flash pulmonary oedema
      or congestive heart failure (CHF) and renal insufficiency. METHODS AND RESULTS:
      We searched online databases (PubMed and ClinicalTrials.gov) and references of
      included articles. We included 25 articles describing 79 patients with RAS and
      flash oedema and seven articles describing 94 patients with RAS, CHF, and renal
      insufficiency. According to the Grading of Recommendations Assessment,
      Development, and Evaluation (GRADE) system, the quality of the evidence was, at
      best, low. Seventy-six per cent of patients with flash oedema did not have any
      recurrence after angioplasty. Recurrence of symptoms was associated with either
      restenosis of the renal artery or cardiac arrhythmias in all patients. In the
      patients with CHF and renal insufficiency, the severity of heart failure
      symptoms, expressed as New York Heart Association (NYHA) functional class,
      improved after angioplasty in all included articles. CONCLUSION: The evidence
      included in this systematic review justifies a weak recommendation in favour of
      angioplasty in patients with atherosclerotic RAS and either flash pulmonary
      oedema or CHF and renal insufficiency.

PMID- 22455867
TI  - Effect of acute ethanol treatment on biochemical and histopathological factors in
      rat liver in an experimental sepsis model.
AB  - The aim of this study was to investigate the contribution of acute alcohol in
      sepsis-related liver damages using a Cecal Ligation and Puncture (CLP) model.
      Rats were divided into 7 groups (5 rats/group): control (saline-injected), sham
      operated, CLP, ethanol (1.0 and 2.0 g/kg b.w) and CLP+ethanol. The CLP+ethanol
      group received a single dose of ethanol following sepsis induction. Sepsis
      induction caused early changes in lipid peroxidation products in liver, whereas
      ethanol alone (2.0 g/kg b.w) resulted in a significant increase (~21%) in lipid
      peroxidation, which was further increased (~57%) in CLP rats treated with
      alcohol. CLP operation and alcohol treatment exhibited additive effects on plasma
      catalase, liver glutathione and glutathione S-transferase (GST), which were
      primarily suppressed due to ethanol. Hepatic cytochrome P4501A1, which was
      elevated in CLP rats, was reversed in the CLP+ethanol group. Plasma tumor
      necrosis factor-alpha was markedly elevated (~85%) in septic rats, but was
      unaffected in septic rats having received ethanol. Histopathological observations
      revealed that inflammatory reactions in liver in response to CLP operation are
      not intensified by ethanol administration. On the basis of biochemical and
      histopathological results, it can be concluded that acute ethanol treatment is
      responsible for early changes in oxidative stress, which may lead to
      polymicrobial sepsis-related organ damage.

PMID- 22455868
TI  - IRF7, a functional factor associates with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is an autoimmune disease attributing to a
      combination of genetic and environmental factors. Abnormal expression/function of
      type I interferons has been demonstrated with the pathogenesis of SLE, especially
      IFN-alpha, which can be regulated by IFN regulatory factor 7 (IRF7). Single
      nucleotide polymorphisms (SNPs) near/in IRF7 have been substantiated related to
      onset of SLE, moreover, regulation of IRF7 expression/function has been found
      important in SLE. Therefore, we will discuss the association of IRF7 and SLE
      based on recent understandings to render more information about the mechanisms of
      IRF7 might perform in.

PMID- 22455870
TI  - WITHDRAWN: Phytochemical Society of North America.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 22455869
TI  - Sentinel lymph node biopsy using a new indocyanine green fluorescence imaging
      system with a colour charged couple device camera for oral cancer.

PMID- 22455871
TI  - Light quality affects flavonoid biosynthesis in young berries of Cabernet
      Sauvignon grape.
AB  - Biosynthesis of phenolic compounds is known to be sensitive to light
      environments, which reflects the possible role of these compounds for
      photoprotection in plants. Herein, the effects of UV and visible light on
      biosynthesis of flavonoids was investigated, i.e., proanthocyanidins (PAs) and
      flavonols, in young berry skins of a red-wine grape, Vitis vinifera cv. Cabernet
      Sauvignon. Shading with light-proof boxes from the flowering stage until 49 days
      after treatment (DAT) partially decreased PA concentrations, and completely
      decreased flavonol concentrations in the berry skins. Shading decreased the
      transcript abundance of a flavonol-related gene more remarkably than those of PA
      related genes. In addition, light exclusion influenced the composition of PAs,
      such as the decrease in the proportion of trihydroxylated subunits and the mean
      degree of polymerization (mDP) within PAs. However, solar UV exclusion did not
      affect the concentration and composition of PAs, whereas this exclusion
      remarkably decreased the flavonol concentration. Consistently, UV exclusion did
      not influence the transcript levels of PA-related genes, whereas it dramatically
      decreased that of flavonol-related genes. These findings indicated a different
      light regulation of the biosynthesis of these flavonoids in young berry skins of
      wine grape. Visible light primarily induces biosynthesis of PAs and affects their
      composition, whereas UV light specifically induces biosynthesis of flavonols.
      Distinct roles of members of a MYB transcription factor family for light
      regulation of flavonoid biosynthesis were proposed.

PMID- 22455872
TI  - InTERTesting association between telomerase, mTOR and phytochemicals.
AB  - Telomeres are stretches of repeated DNA sequences located at the ends of
      chromosomes that are necessary to prevent loss of gene-coding DNA regions during
      replication. Telomerase - the enzyme responsible for immortalising cancer cells
      through the addition of telomeric repeats - is active in ~90% of human cancers.
      Telomerase activity is inhibited by various phytochemicals such as isoprenoids,
      genistein, curcumin, epigallocatechin-3-gallate, resveratrol and others. Human
      TERT (telomerase reverse transcriptase - the rate-limiting component of
      telomerase), heat shock protein 90, Akt, p70 S6 kinase (S6K) and mammalian target
      of rapamycin (mTOR) form a physical and functional complex with one another. The
      inclusion of Akt, mTOR and S6K in the TERT complex is compelling evidence to
      support mTOR-mediated control of telomerase activity. This review will define the
      role of mTOR, the master regulator of protein translation, in telomerase
      regulation and provide additional insights into the numerous ways in which
      telomerase activity is hindered by phytochemicals.

PMID- 22455873
TI  - [11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux
      transporter P-glycoprotein.
AB  - BACKGROUND: [11C]Flumazenil and positron emission tomography (PET) are used
      clinically to assess gamma-aminobutyric acid (GABA)-ergic function and to
      localize epileptic foci prior to resective surgery. Enhanced P-glycoprotein (P
      gp) activity has been reported in epilepsy and this may confound interpretation
      of clinical scans if [11C]flumazenil is a P-gp substrate. The purpose of this
      study was to investigate whether [11C]flumazenil is a P-gp substrate. METHODS:
      [11C]Flumazenil PET scans were performed in wild type (WT) (n = 9) and Mdr1a/1b,
      (the genes that encode for P-gp) double knockout (dKO) (n = 10) mice, and in
      naive rats (n = 10). In parallel to PET scanning, [11C]flumazenil plasma
      concentrations were measured in rats. For 6 of the WT and 6 of the dKO mice a
      second, [11C]flumazenil scan was acquired after administration of the P-gp
      inhibitor tariquidar. Cerebral [11C]flumazenil concentrations in WT and Mdr1a/1b
      dKO mice were compared (genetic disruption model). Furthermore, pre and post P-gp
      blocking cerebral [11C]flumazenil concentrations were compared in all animals
      (pharmacological inhibition model). RESULTS: Mdr1a/1b dKO mice had approximately
      70% higher [11C]flumazenil uptake in the brain than WT mice. After administration
      of tariquidar, cerebral [11C]flumazenil uptake in WT mice increased by about 80%
      in WT mice, while it remained the same in Mdr1a/1b dKO mice. In rats, cerebral
      [11C]flumazenil uptake increased by about 60% after tariquidar administration.
      Tariquidar had only a small effect on plasma clearance of flumazenil.
      CONCLUSIONS: The present study showed that [11C]flumazenil is a P-gp substrate in
      rodents. Consequently, altered cerebral [11C]flumazenil uptake, as observed in
      epilepsy, may not reflect solely GABAA receptor density changes but also changes
      in P-gp activity.

PMID- 22455874
TI  - Safety considerations in the management of allergic diseases: focus on
      antihistamines.
AB  - OBJECTIVE: To conduct a systematic review of evidence supporting the safety
      profiles of frequently used oral H(1)-antihistamines (AHs) for the treatment of
      patients with histamine-release related allergic diseases, e.g. allergic rhinitis
      and urticaria, and to compare them to the safety profiles of other medications,
      mostly topical corticosteroids and leukotriene antagonists (LTRA). RESEARCH
      DESIGN AND METHODS: Systematic search of the published literature (PubMed) and of
      the regulatory authorities databases (EMA and FDA) for oral AHs. RESULTS:
      Similarly to histamine, antihistamines (AHs) have organ-specific efficacy and
      adverse effects. The peripheral H(1)-receptor (PrH1R) stimulation leads to
      allergic symptoms while the brain H(1)-receptor (BrH1R) blockade leads to
      somnolence, fatigue, increased appetite, decreased cognitive functions (impaired
      memory and learning), seizures, aggressive behaviour, etc. First-generation oral
      AHs (FGAHs) inhibit the effects of histamine not only peripherally but also in
      the brain, and additionally have potent antimuscarinic, anti-alpha-adrenergic and
      antiserotonin effects leading to symptoms such as visual disturbances (mydriasis,
      photophobia, and diplopia), dry mouth, tachycardia, constipation, urinary
      retention, agitation, and confusion. The somnolence caused by FGAHs interferes
      with the natural circadian sleep-wake cycle and therefore FGAHs are not suitable
      to be used as sleeping pills. Second-generation oral AHs (SGAHs) have proven
      better safety and tolerability profiles, much lower proportional impairment
      ratios, with at least similar if not better efficacy, than their predecessors.
      Only SGAHs, and especially those with a proven long-term (e.g., >=12 months)
      clinical safety, should be prescribed for young children. Evidence exist that
      intranasally applied medications, like intranasal antihistamines, have the
      potential to reach the brain and cause somnolence. CONCLUSIONS: Second-generation
      oral antihistamines are the preferred first-line treatment option for allergic
      rhinitis and urticaria. Patients taking SGAHs report relatively little and mild
      adverse events even after long-term continuous treatments. An antihistamine
      should ideally possess high selectivity for the H(1)-receptor, high PrH1R
      occupancy and low to no BrH1R occupancy.

PMID- 22455875
TI  - Russian Federation. Health system review.
AB  - The HiT reviews are country-based reports that provide a detailed description of
      a health system and of policy initiatives in progress or under development. HiTs
      examine different approaches to the organization, financing and delivery of
      health services and the role of the main actors in health systems; describe the
      institutional framework, process, content and implementation of health and health
      care policies; and highlight challenges and areas that require more in-depth
      analysis. At independence from the Soviet Union in 1991, the Russian health
      system inherited an extensive, centralized Semashko system, but was quick to
      reform health financing by adopting a mandatory health insurance (MHI) model in
      1993. MHI was introduced in order to open up an earmarked stream of funding for
      health care in the face of severe fiscal constraints. While the health system has
      evolved and changed significantly since the early 1990 s, the legacy of having
      been a highly centralized system focused on universal access to basic care
      remains. High energy prices on world markets have ensured greater macroeconomic
      stability, a budget surplus and improvements in living standards for most of the
      Russian population. However, despite an overall reduction in the poverty rate,
      there is a marked urban rural split and rural populations have worse health and
      poorer access to health services than urban populations. The increase in
      budgetary resources available to policy-makers have led to a number of recent
      federal-level health programmes that have focused on the delivery of services and
      increasing funding for priority areas including primary care provision in rural
      areas. Nevertheless, public health spending in the Russian Federation remains
      relatively low given the resources available. However, it is also clear that,
      even with the current level of financing, the performance of the health system
      could be improved. Provider payment mechanisms are the main obstacle to improving
      technical efficiency in the Russian health system, as most budget funding
      channelled through local government is input based. For this reason, the most
      recent reforms as well as legislation in the pipeline seek to ensure all health
      care funding is channelled through a strengthened MHI system with contracts for
      provider payments being made using output-based measures.

PMID- 22455876
TI  - Chronic allergic-like inflammation in the tumor stroma of human gastric
      carcinomas: an ultrastructural study.
AB  - Inflammatory cell infiltration around the sites of carcinoma invasion is believed
      to play important roles in tumor biological behavior. The status of inflammatory
      cell infiltration at the sites of frank invasion in 92 cases of gastric
      carcinomas was examined, with special emphasis on tumor-associated tissue
      eosinophilia (TATE). TATE was found in 7 out of 92 (7.6%) gastric carcinomas (6
      of intestinal-type and 1 of diffuse-type). Electron microscopy, selectively
      performed in the 7 cases of gastric carcinomas with TATE, showed that eosinophils
      participated in the stromal reaction by interacting with tumor cells, mast cells,
      and each other. Most of the tumor-infiltrating mast cells exhibited anaphylactic
      or piecemeal degranulation, indicating that the mast cells had been activated in
      situ. Some mast cells were noted in close contact to viable tumor cells,
      suggesting the existence of direct cell-to-cell interactions. There was also
      extracellular deposition of free eosinophil granules and Charcot-Leyden crystals.
      These morphologic findings are similar to that described in late/chronic-phase
      allergic reaction in both human and experimental animals, where angiogenesis and
      fibrosis/tissue repair are also present. In conclusion, TATE may indicate a
      chronic allergic-like Th2 host-tumor reaction, and understanding these pathways
      should create tools to enhance defence and contrast neoplastic disease.

PMID- 22455877
TI  - Morphological and functional adaptation of the maternal heart during pregnancy.
AB  - BACKGROUND: Pregnancy provides a unique model to study the adaptation of the
      heart in a physiological situation of transient load changes. The aim of this
      study was to assess the performance of the left ventricle (LV) in normal,
      uncomplicated pregnancies while considering the actual LV load and shape. METHODS
      AND RESULTS: Serial echocardiographic examinations were performed in 51 women in
      each pregnancy trimester and 3 to 6 months after delivery. Data from 10
      nulliparous, age-matched women were used as the control. Conventional parameters
      of LV function (ejection fraction) as well as myocardial deformation (strain)
      were interpreted, taking into consideration maternal hemodynamics and LV shape.
      Cardiac output increased during pregnancy because of a higher stroke volume in
      early pregnancy and a late increase in heart rate, whereas total vascular
      resistance decreased. Progressive development of eccentric hypertrophy was
      observed, which subsequently recovered postpartum. Sphericity index decreased
      from the first to the third trimester (1.92+/-0.17 versus 1.71+/-0.17) and
      returned postpartum to values comparable to the control. Although higher LV
      stroke work was noted toward the third trimester (5.9+/-1.1 versus 5.3+/-1.0
      Newton meter, P<0.001), ejection fraction showed no significant changes. LV
      strain decreased significantly in late pregnancy (-19.5+/-2% to -17.6+/-1.6%,
      P<0.001) and returned to baseline values after delivery (-19.5+/-2%).
      CONCLUSIONS: Pregnancy is a physiological process associated with increased
      cardiac performance and progressive LV remodeling. These changes are not directly
      reflected by parameters traditionally considered to describe systolic function,
      such as ejection fraction and longitudinal deformation. While ejection fraction
      was insensitive to the functional changes, the transient decrease in longitudinal
      deformation becomes only plausible when considering the changes in LV geometry.

PMID- 22455878
TI  - Efficient and robust RNA-seq process for cultured bacteria and complex community
      transcriptomes.
AB  - We have developed a process for transcriptome analysis of bacterial communities
      that accommodates both intact and fragmented starting RNA and combines efficient
      rRNA removal with strand-specific RNA-seq. We applied this approach to an RNA
      mixture derived from three diverse cultured bacterial species and to RNA isolated
      from clinical stool samples. The resulting expression profiles were highly
      reproducible, enriched up to 40-fold for non-rRNA transcripts, and correlated
      well with profiles representing undepleted total RNA.

PMID- 22455879
TI  - Neuroglia at the crossroads of homoeostasis, metabolism and signalling: evolution
      of the concept.
AB  - Ever since Rudolf Virchow in 1858 publicly announced his apprehension of
      neuroglia being a true connective substance, this concept has been evolving to
      encompass a heterogeneous population of cells with various forms and functions.
      We briefly compare the 19th-20th century perspectives on neuroglia with the up-to
      date view of these cells as an integral, and possibly integrating, component of
      brain metabolism and signalling in heath and disease. We conclude that the
      unifying property of otherwise diverse functions of various neuroglial cell sub
      types is to maintain brain homoeostasis at different levels, from whole organ to
      molecular.

PMID- 22455880
TI  - [Issues on renal biopsy diagnosis].

PMID- 22455881
TI  - [Chromophobe renal cell carcinoma: a clinicopathologic study and immunophenotypes
      of 42 cases].
AB  - OBJECTIVE: To study the clinicopathologic features, immunohistochemical profiles
      and prognosis of chromophobe renal cell carcinoma (ChRCC). METHODS: Forty-two
      cases of ChRCC were retrieved from the archival files of the Affiliated Hospital
      of Qingdao University, 401 Hospital of PLA and Qingdao Municipal Hospital from
      2003 to 2011. The clinical and pathologic features of the tumors were reviewed.
      Hale colloidal iron staining was performed and EnVision immunohistochemistry was
      used to detect the expression of a series of immunologic markers. Forty cases of
      clear cell renal cell carcinoma and 10 cases of renal oncocytoma were selected as
      controls. RESULTS: The patients included 17 males and 25 females. The age of
      patients ranged from 39 years to 78 years (median age = 57 years). On gross
      examination, the tumors ranged from 2 cm to 19 cm in greatest dimension (mean
      size = 7.3 cm). Histologically, the tumors were mainly composed of solid sheets,
      acini or tubules of malignant cells. The tumor cells contained clear finely
      reticular ("chromophobe") and eosinophilic cytoplasm with perinuclear clearing.
      The nuclear outline was irregular and wrinkled. Nucleoli were inconspicuous and
      mitotic figures were barely seen. Hale colloidal iron stain was positive in all
      cases. Immunohistochemically, the tumor cells were variably positive for EMA
      (100%, 42/42), CK7 (95.2%, 40/42), Ksp-cad (92.9%, 39/42), CK18 (88.1%, 37/42),
      CD117 (61.9, 26/42), CD10 (31.0%, 13/42) and PAX2 (28.6%, 12/42). They were
      negative for vimentin, CA IX and TFE3. The follow-up period in 31 patients ranged
      from 2 to 77 months (average duration = 29 months). Three patients died of tumor
      metastasis 3, 8, 13 months respectively after the operation. Twenty-eight
      patients were still alive without evidence of tumor recurrence. CONCLUSIONS:
      ChRCC predominantly occurs in middle-aged and elderly patients. It often carries
      a favorable prognosis. The presence of plant cell-like morphology, pale cells
      with uniform reticular microvesicular appearance and perinuclear clearing are
      characteristic histologic features. The diffuse positivity for Hale colloidal
      iron stain and EMA/CK7/Ksp-cadherin/CD117-positive immunoprofiles are also useful
      in differential diagnosis.

PMID- 22455882
TI  - [Expression of neonatal Fc receptor on human nephritis and rat nephritis models].
AB  - OBJECTIVE: To study the expression of neonatal Fc receptor in podocytes in human
      nephritis and immune-induced rat nephritis models: anti-Thy1.1 nephritis and
      Heymann nephritis. METHODS: Thirty-nine cases of renal biopsies were enrolled
      from September 2009 to February 2010, including 8 cases of minimal change
      disease, 4 cases of focal segmental glomerulosclerosis, 9 cases of membranous
      nephropathy, 12 cases of IgA nephropathy and 6 cases of lupus nephritis. Five
      normal kidney tissue samples adjacent to renal clear-cell carcinoma were served
      as normal controls. Laser capture microdissection and real-time RT-PCR were used
      to assess the expression level of FcRn mRNA in glomeruli of various
      glomerulonephritides, and immunohistochemistry (IHC) of FcRn by SuperVision
      method was performed. In addition, rat models of mesangial proliferative
      nephritis (anti-Thy1.1 nephritis) and passive membranous nephropathy (Heymann
      nephritis) were established and FcRn was examined in renal tissues by IHC.
      RESULTS: The FcRn mRNA level in lupus nephritis was statistically higher than
      that of normal controls (P < 0.05). FcRn protein expression by IHC was seen in
      lupus nephritis (6/6), membranous nephropathy (6/9) and IgA nephropathy (7/12),
      significantly higher than that of normal controls (0/5), P < 0.05. Minimal change
      disease and focal segmental glomerular sclerosis showed minimal or none
      expression of FcRn (1/8, 0/4 respectively) and not statistically difference from
      that of normal controls. Furthermore, FcRn expression in podocytes was detected
      in rat anti-Thy1.1 (3/5) and Heymann nephritis models (2/7) but was not detected
      in normal controls. CONCLUSIONS: Expression of FcRn in podocytes was up-regulated
      in immune-induced human nephritis and rat nephritis models of anti-Thy1.1
      nephritis and Heymann nephritis. FcRn may play a role in the development of
      immune-induced glomerulonephritis.

PMID- 22455883
TI  - [Expression and significance of p-AKT, p-GSK3beta and beta-catenin in epithelial
      carcinoma of ovary].
AB  - OBJECTIVE: To investigate the expressions of phosphorylated protein kinase B (p
      AKT), phosphorylated glycogen synthase kinase 3beta (p-GSK3beta) and beta-catenin
      proteins and to evaluate their relationship with the clinical pathological
      characteristics in epithelial tumors of the ovary. METHODS: The expression of p
      AKT, p-GSK3beta, and beta-catenin was detected with immunohistochemical staining
      (EnVision method) in 10 cases of benign epithelial neoplasia, 10 cases of
      borderline epithelial neoplasia and 70 cases of ovarian carcinoma. The
      relationship of the expression of p-AKT, p-GSK3beta and beta-catenin with the
      clinical pathological features was analyzed. RESULTS: The positive expression
      rates of p-AKT, p-GSK3beta and beta-catenin in epithelial ovarian carcinoma were
      67.1% (47/70), 60.0% (42/70) and 71.4% (50/70), respectively. Compared to the
      results of benign and borderline epithelial neoplasia, the expression of the
      three proteins in carcinoma of the ovary was significantly different (all P <
      0.05).Positive correlation was found between p-AKT and p-GSK3beta, p-GSK3beta and
      beta-catenin, and p-AKT and beta-catenin in epithelial ovarian carcinoma (r =
      0.546, 0.581, 0.500, respectively; all P < 0.05). Compared to the results of
      benign and borderline epithelial neoplasia, the expression of p-AKT protein in
      epithelial ovarian carcinoma was significantly different (all P < 0.05). The
      expression of p-AKT was correlated with the differentiation of epithelial ovarian
      carcinoma (P < 0.05), but no relationship was found between its expression and
      histological classification and FIGO staging (P > 0.05). The expression of p
      GSK3beta and beta-catenin in epithelial ovarian carcinoma were both higher than
      that in benign and borderline epithelial neoplasia (P < 0.05), and correlated
      with tumor differentiation and FIGO staging (P < 0.05), but no relationship were
      found between their expression with histological classification (P > 0.05).
      CONCLUSIONS: Positive correlations are found between p-AKT, p-GSK3beta and beta
      catenin in epithelial ovarian carcinoma. The activation of beta-catenin is
      possibly correlated with inactivation of p-GSK3beta that binds to p-AKT.

PMID- 22455884
TI  - [Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical
      analysis of 258 cases].
AB  - OBJECTIVES: To observe the clinicopathologic features of Langerhans cell
      histiocytosis (LCH), and to evaluate the values of langerin, CD1a and S-100
      protein expression in diagnosis of the tumor. METHODS: Total 258 cases of
      Langerhans cell histiocytosis in the past 18 years (from 1992 to 2008) were
      collected, morphologic review and immunohistochemical staining were performed.
      RESULTS: In all 258 cases, the ages of patients older than 16 years or younger
      than 2 years were 126 (48.8%) and 37 (14.3%), respectively, in the remaining 95
      (36.8%) of the cases, the age of the patients ranged from 2 to 16 years. For all
      of 258 cases, there were 364 diseased sites. Bony lesions accounted for 77.2%
      (281 cases), especially the skull (112 cases, 39.9%), followed by lymph node (25
      cases, 6.9%) and skin (14 cases, 3.8%). Clinically, unisystem or unifocal disease
      was predominant (201 cases, 77.9%), followed by unisystem and multifocal disease
      (21 cases, 8.1%), multi-system disease (26 cases, 10.1%), isolated pulmonary LCH
      (2 cases, 0.8%), and unclassified (8 cases, 3.1%). Histologically, variable
      number of Langerhans cells was present in 265 samples of 258 cases.
      Multinucleated giant cells were found in 166 (62.6%) of the samples. Eosinophils
      were the major infiltrating non-neoplastic cells, and eosinophilic abscess was
      seen in 57 cases (21.5%). Coagulative necrosis and dead bone were detected in 29
      (10.9%) and 124 (46.8%) of the cases, respectively. Immunohistochemically, the
      expression of S-100 protein, CD1a and langerin was 99.1% (209/211), 100%
      (206/206) and 98.5% (193/196), respectively, and the sensitivity of them had no
      statistical difference. CONCLUSIONS: In this group of LCH cases, the ratio of
      adult patients is high, but the proportion of multi-organ lesion is low. No
      significant difference of the sensitivity is found among langerin, CD1a and S-100
      expression in diagnosis of LCH.

PMID- 22455885
TI  - [Clinical and pathologic features of gastric schwannoma].
AB  - OBJECTIVE: To study the clinical and pathologic features of gastric schwannomas.
      METHODS: The macroscopic and microscopic features of 9 cases of gastric
      schwannoma were analyzed. Immunohistochemical study for S-100 protein, CD117,
      CD34, neurofilament, desmin, nestin, glial fibrillary acidic protein, platelet
      derived growth factor-alpha (PDGFR-alpha) and vimentin was carried out. Mutation
      analysis of c-kit gene (exon 9, 11, 13 and 17) and PDGFR-alpha gene (exon 12 and
      18) in 1 case was examined by PCR amplification and direct sequencing. RESULTS:
      The patients included 5 males and 4 females. The age of patients ranged from 42
      to 81 years (median = 56.5 years). The size of the tumors ranged from 2 to 9 cm
      in greatest diameter. Follow-up data in 8 cases (from 1 month to 65 months)
      showed no evidence of recurrence or metastasis. Gross examination showed that
      gastric schwannomas were homogeneous, firm, yellow-white and bore no true fibrous
      capsule. Histologically, all cases were composed of fascicles of spindle cells
      associated with nuclear palisading, Verocay body formation and peripheral cuff of
      reactive lymphoid aggregates. Some of them showed degenerative changes including
      cyst formation, calcification, hemorrhage, necrosis and hyalinization.
      Immunohistochemical study showed that the tumor cells were strongly positive for
      S-100 protein and vimentin. There was various degree of staining for nestin (8/9)
      and glial fibrillary acidic protein (6/9). They were negative for CD117, CD34,
      neurofilament, desmin and smooth muscle actin. One case showed focal positivity
      for PDGFR-alpha (1/9), with no mutations found. CONCLUSIONS: Gastric schwannomas
      share similar histologic features with conventional soft tissue schwannomas, in
      addition to the presence a reactive lymphoid cuff. The clinical, macroscopic,
      histologic and immunohistochemical features of gastric schwannomas were different
      from those of gastrointestinal stromal tumors and leiomyomas.

PMID- 22455886
TI  - [Study on clinicopathologic grading system and prognosis of primary hepatic
      neuroendocrine neoplasms].
AB  - OBJECTIVE: To study the clinicopathologic features, criteria for grading and
      prognostic factors of primary hepatic neuroendocrine neoplasms. METHODS: Thirty
      five cases of primary hepatic neuroendocrine neoplasm were retrieved from the
      archival files over a period of 11 years (with 32 cases having integrated data).
      According to the 2010 WHO classification of tumors of the digestive system, the
      cases were categorized into three groups: neuroendocrine tumor grade 1 (NET G1),
      neuroendocrine tumor grade 2 (NET G2) and neuroendocrine carcinoma (NEC).
      Statistical correlation between various histologic parameters and survival data
      was analyzed. RESULTS: Statistical analysis showed significant difference between
      NET [G1 (1 case)/G2 (14 cases)] and NEC (17 cases) groups in terms of tumor
      differentiation, necrosis, nuclear atypia, mitotic count and Ki-67 proliferative
      index (P < 0.05). There was no statistically significant difference in tumor
      size, growth pattern and presence of vascular tumor emboli (P > 0.05). The
      survival rate of patients correlated with tumor differentiation, growth pattern,
      necrosis, nuclear atypia, mitotic count and proliferative index (P < 0.05). There
      was no statistically significant difference between patient survival and tumor
      size or presence of vascular tumor emboli (P > 0.05). CONCLUSIONS: The
      subdivision of primary hepatic neuroendocrine neoplasm according to the 2010 WHO
      classification of tumors of the digestive system helps to evaluate the malignant
      potential and prognosis of the tumors. Prognostically useful histologic
      parameters include tumor differentiation, growth pattern, necrosis, nuclear
      atypia, mitotic count and proliferative index.

PMID- 22455887
TI  - [FTY720 attenuates rat anti-Thy-1 mesangial proliferative glomerulonephritis by
      inhibition of transforming growth factor beta1-connective tissue growth factor
      pathway].
AB  - OBJECTIVE: To investigate whether FTY720 inhibits rat mesangial proliferation and
      extracellular matrix expansion through suppression of transforming growth factor
      beta1-connective tissue growth factor (TGFbeta1-CTGF) pathway, and to explore
      experimental evidence for its effect on mesangial proliferative
      glomerulonephritis. METHODS: A rat model of anti-Thy-1 mesangial proliferative
      glomerulonephritis was established and FTY720 intervention was performed.
      Periphery blood lymphocyte count, urine protein excretion, glomerular mesangial
      proliferation, protein and gene expression of TGFbeta1 and CTGF and extracellular
      matrix protein including fibronectin, laminin and collagen IV in isolated
      glomeruli were documented at 1, 3 and 7 days after injection of anti-Thy-1
      antibody. RESULTS: The model group developed proteinuria at 1, 3 and 7 days after
      injection of anti-Thy-1 antibody, which were significantly higher [(27.9 +/-
      7.3), (63.5 +/- 18.8) and (52.4 +/- 15.4)mg/d, respectively] than those in the
      control group [(8.4 +/- 2.4), (8.4 +/- 2.1) and (10.4 +/- 3.2) mg/d;
      respectively, P < 0.01]. FTY720 intervention group showed significantly decreased
      proteinuria at 3 and 7 days after injection [(31.4 +/- 7.0), (25.5 +/- 7.7) mg/d,
      respectively] than model group (P < 0.01), although higher than the control group
      (P < 0.01). After intervention for 3 and 7 days, FTY720 significantly down
      regulated both TGFbeta1 and CTGF gene and protein expression in cultured
      glomeruli, and suppressed the production of glomerular extracellular matrix
      protein secretion, leading to attenuated mesangial cell proliferation and
      extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative
      glomerulonephritis. CONCLUSION: FTY720 significantly attenuates mesangial
      proliferation and extracellular matrix expansion through inhibition of TGFbeta1
      CTGF pathway in rat, and thus ameliorates the development of anti-Thy-1 mesangial
      proliferative glomerulonephritis.

PMID- 22455888
TI  - [Mechanism of hepatocyte apoptosis in rats with liver fibrosis induced by
      lipogenic methionine-choline-deficient diet].
AB  - OBJECTIVE: To clarify the effects of endoplasmic reticulum stress (ER stress) and
      mitogen-activated protein kinase (MAPK) on hepatocyte apoptosis in rats with non
      alcoholic fatty liver fibrosis induced by methionine-choline-deficient diet
      (MCDD). METHODS: Nonalcoholic steatohepatitis with advanced fibrosis was induced
      in rats by giving a MCDD for 10 weeks (group M). A methionine-choline-control
      diet (MCCD) instead of MCDD was given for the last 2 weeks to the experimental
      group (group R). Steatosis, fibrosis and inflammation were determined by tissue
      staining. The activation of hepatic stellate cells and oxidative stress were
      determined by immunostaining, immunoblotting or real time-PCR (RT-PCR),
      respectively. Hepatocyte apoptosis was determined by TUNEL staining. Expressions
      of glucose-regulated protein 78 (GRP78), caspase-12, caspase-7, cleaved caspase
      7, caspase-3, cleaved caspase-3, and caspase-9 were evaluated to clarify the
      presence of ER stress. Expressions of c-Jun, ERK1/2, p-ERK1/2 were evaluated to
      clarify the states of MAPK signaling. RESULTS: Changing the diet from MCDD to
      MCCD triggered the reduction of fat in hepatocytes, a decrease in inflammatory
      response, oxidative stress, and fibrosis. The protein expressions of ERP78,
      caspase-12, caspase-7, and cleaved caspase-7 were increased significantly in
      group M compared with normal control group (group N, P < 0.05 or P < 0.01), the
      mRNA expressions of ERP78, caspase-12, and caspase-7 were also increased
      significantly in group M compared with group N (3.03 +/- 0.41 vs 2.12 +/- 0.37,
      1.86 +/- 0.36 vs 0.78 +/- 0.20, and 2.38 +/- 0.19 vs 1.84 +/- 0.13, respectively,
      P < 0.05 or P < 0.01), while they recovered immediately in group R. In contrast,
      the protein levels of caspase-3, cleaved caspase-3 and mRNA expressions of
      caspase-3 and caspase-9 revealed no significant differences in three groups (P >
      0.05). The mRNA expressions of c-Jun and protein levels of ERK1 and p-ERK1 were
      increased significantly in group M compared with group N (P < 0.01), while they
      recovered immediately after changing the diet from MCDD to MCCD. CONCLUSIONS: ER
      stress plays a role in the development and regression of non-alcoholic fatty
      liver fibrosis induced by MCDD, however, ER stress-related caspase-12 pathway may
      not be the main mechanism of hepatic apoptosis, and MAPK signaling may play an
      important role in hepatic apoptosis in the model.

PMID- 22455889
TI  - [Clinicopathologic features of metanephric adenoma].

PMID- 22455890
TI  - [hTERC gene amplification and expression of human papillomavirus in cervical
      carcinogenesis].

PMID- 22455891
TI  - [Clinical and pathologic characteristics of 4 cases of Wegener's granulomatosis
      associated with specific pathogenic infections].

PMID- 22455892
TI  - [Papillary cystadenoma of epididymis in von Hippel-Lindau syndrome: report of a
      case].

PMID- 22455893
TI  - [Verruciform xanthoma of glans penis: report of a case].

PMID- 22455894
TI  - [Alveolar rhabdomyosarcoma of left testis: report of a case].

PMID- 22455895
TI  - [Histiocytic sarcoma of stomach: report of a case].

PMID- 22455896
TI  - [Thymoma with extensive coagulation necrosis: report of two cases].

PMID- 22455897
TI  - [Granuloma-like interdigitating dendritic cell sarcoma: report of a case].

PMID- 22455898
TI  - [Carcinoma showing thymus-like element: report of a case].

PMID- 22455899
TI  - [Primary hemangiopericytoma of bone: report of a case].

PMID- 22455900
TI  - [Autoimmune pancreatitis: report of a case].

PMID- 22455901
TI  - [Correlation between carcinoma-associated fibroblasts and breast cancer].

PMID- 22455902
TI  - [Asymmetric hypertrophy of the masticatory muscles].
AB  - INTRODUCTION: Hypertrophy of the masticatory muscles most commonly affects the
      masseter. Less common cases of isolated or associated temporalis hypertrophy are
      also reported. Parafunctional habits, and more precisely bruxism, can favor the
      onset of the hypertrophy. This condition is generally idiopathic and can require
      both medical and/or surgical management. OBSERVATION: A 29-year-old patient was
      referred to our department for an asymmetric swelling of the masticatory muscles.
      Physical examination revealed a bilateral hypertrophy of the masticatory muscles,
      predominantly affecting the right temporalis and the left masseter. Major bruxism
      was assessed by premature dental wearing. The additional examinations confirmed
      the isolated muscle hypertrophy. Benign asymmetric hypertrophy of the masticatory
      muscles promoted by bruxism was diagnosed. Treatment with injections of type A
      botulinum toxin was conducted in association with a splint and relaxation. Its
      effectiveness has been observed at six months. DISCUSSION: Few cases of
      unilateral or bilateral temporalis hypertrophy have been reported, added to the
      more common isolated masseter muscles hypertrophy. The diagnosis requires to rule
      out secondary hypertrophies and tumors using Magnetic Resonance Imaging. The
      condition is thought to be favoured by parafunctional habits such as bruxism. The
      conservative treatment consists in reducing the volume of the masticatory muscles
      using intramuscular injections of type A botulinum toxin. Other potential
      conservative treatments are wearing splints and muscle relaxant drugs. Surgical
      procedures aiming to reduce the muscle volume and/or the bone volume (mandibular
      gonioplasty) can be proposed.

PMID- 22455903
TI  - Expression patterns of Notch receptors and their ligands in human osteoarthritic
      and healthy articular cartilage.
AB  - Notch pathway plays a pivotal role in cell fate determination. There is much
      interest surrounding its therapeutic potential, in osteoarthritis, but the
      expression profile of Notch-related molecules, as well as their relation with
      cartilage pathological parameters, remains unclear. The purpose of our study is
      to analyze the expression pattern of Notch family members, type II and type I
      collagen, in normal (healthy) and osteoarthritic human knee cartilage.
      Osteoarthritic cartilages were obtained from 3 patients undergoing a total knee
      replacement. Macroscopically normal cartilage was dissected from 3 human knees at
      the time of autopsy or surgery. Immunohistochemical staining was performed using
      Notch1,2,3 and 4, Delta, Jagged, type II collagen and type I collagen antibodies.
      In healthy cartilage, type II collagen was abundantly expressed while type I was
      absent. This latter increased proportionally to the osteoarthritic grade. Type II
      collagen expression remained intense in osteoarthritic cartilage. In healthy
      cartilage as well as in cartilage with minor lesions, Notch family member's
      proteins were not or just weakly expressed at the surface and in the cells.
      However, Notch molecules were over-expressed in osteoarthritic cartilage compared
      to healthy one. This expression pattern was different according to the cartilage
      zone and the severity of OA. Our data suggest that Notch signaling is activated
      in osteoarthritic cartilage, compared to healthy cartilage, with a much more
      abundant expression in the most damaged areas.

PMID- 22455904
TI  - DNA binding by the plant-specific NAC transcription factors in crystal and
      solution: a firm link to WRKY and GCM transcription factors.
AB  - NAC (NAM/ATAF/CUC) plant transcription factors regulate essential processes in
      development, stress responses and nutrient distribution in important crop and
      model plants (rice, Populus, Arabidopsis), which makes them highly relevant in
      the context of crop optimization and bioenergy production. The structure of the
      DNA-binding NAC domain of ANAC019 has previously been determined by X-ray
      crystallography, revealing a dimeric and predominantly beta-fold structure, but
      the mode of binding to cognate DNA has remained elusive. In the present study,
      information from low resolution X-ray structures and small angle X-ray scattering
      on complexes with oligonucleotides, mutagenesis and (DNase I and uranyl photo-)
      footprinting, is combined to form a structural view of DNA-binding, and for the
      first time provide experimental evidence for the speculated relationship between
      plant-specific NAC proteins, WRKY transcription factors and the mammalian GCM
      (Glial cell missing) transcription factors, which all use a beta-strand motif for
      DNA-binding. The structure shows that the NAC domain inserts the edge of its core
      beta-sheet into the major groove, while leaving the DNA largely undistorted. The
      structure of the NAC-DNA complex and a new crystal form of the unbound NAC also
      indicate limited flexibility of the NAC dimer arrangement, which could be
      important in recognizing suboptimal binding sites.

PMID- 22455905
TI  - Use of the Gait Deviation index for the evaluation of patients with Parkinson's
      disease.
AB  - The authors aimed to determine whether the Gait Deviation Index (GDI) could be
      feasible to characterize gait in patients with Parkinson's disease (PD) and
      evaluate outcomes of levodopa treatment. Twenty-two PD participants were
      evaluated with clinical examination and 3-D quantitative gait analysis (GDI was
      calculated from gait analysis) in 2 states (OFF and ON) after taking levodopa.
      Twenty age-matched healthy participants (CG) were included as controls. The GDI
      value in the OFF state was 83.4 +/- 11.5 (statistically different from CG) while
      clinical scales demonstrated a moderate-severe gait impairment of these patients.
      Significant improvements are evident from clinical scores and by GDI values in
      the ON state. The mean GDI for the ON state (GDI(ON): 87.9 +/- 10.4) was
      significantly higher than in for the OFF state (GDI(OFF): 83.4 +/- 11.5),
      indicating a global gait improvement after the treatment. The results show that
      GDI has lower value as an indicator of pathology in PD patients than in
      quantifying the effects of levodopa treatment in PD state.

PMID- 22455906
TI  - Response to a pure tone in a nonlinear mechanical-electrical-acoustical model of
      the cochlea.
AB  - In this article, a nonlinear mathematical model is developed based on the
      physiology of the cochlea of the guinea pig. The three-dimensional intracochlear
      fluid dynamics are coupled to a micromechanical model of the organ of Corti and
      to electrical potentials in the cochlear ducts and outer hair cells (OHC). OHC
      somatic electromotility is modeled by linearized piezoelectric relations whereas
      the OHC hair-bundle mechanoelectrical transduction current is modeled as a
      nonlinear function of the hair-bundle deflection. The steady-state response of
      the cochlea to a single tone is simulated in the frequency domain using an
      alternating frequency time scheme. Compressive nonlinearity, harmonic distortion,
      and DC shift on the basilar membrane (BM), tectorial membrane (TM), and OHC
      potentials are predicted using a single set of parameters. The predictions of the
      model are verified by comparing simulations to available in vivo experimental
      data for basal cochlear mechanics. In particular, the model predicts more
      amplification on the reticular lamina (RL) side of the cochlear partition than on
      the BM, which replicates recent measurements. Moreover, small harmonic distortion
      and DC shifts are predicted on the BM, whereas more significant harmonic
      distortion and DC shifts are predicted in the RL and TM displacements and in the
      OHC potentials.

PMID- 22455907
TI  - Analytical distribution and tunability of noise in a model of promoter progress.
AB  - Chromatin template (CT), which accumulates over time until the promoter becomes
      active, determines upstream dynamics of transcription, but how upstream
      sequential steps impact downstream dynamics qualitatively and quantitatively is
      unclear. Here, we analyze a stochastic gene model with a simple yet typical CT
      that contains one active state and several inactive states of the promoter. We
      derive the analytical expressions for the noise in mRNA probability distributions
      governed by master equations. The derived results extend previous work by
      including the effects of promoter progress on variability and bimodality.
      Specifically, given a CT for transcription, we analytically demonstrate that
      inactive phases of the promoter can modulate the noise intensity to the minimum
      independently of the mean expression of mRNA. If one new inactive state is added
      to the CT, then the resulting noise will be reduced, implying that the multi-off
      mechanism plays a role of attenuating the noise. In contrast to the simple on-off
      mechanism, the multi-off mechanism can also narrow bimodal regions in a certain
      parameter plane and obscure two peaks, explaining why bimodal distributions are
      rarely observed in experiments. Our results provide insight into the role of
      promoter progress in determining the level of cell-to-cell variability in gene
      expression.

PMID- 22455908
TI  - Ultraviolet light transmission through the human corneal stroma is reduced in the
      periphery.
AB  - This article investigates in vitro light transmission through the human cornea in
      the ultraviolet (UV) portion of the electromagnetic spectrum as a function of
      position across the cornea from center to periphery. Spectrophotometry was used
      to measure UV transmission in the wavelength range 310-400 nm, from the central
      cornea to its periphery. UV transmission decreases away from the center, and this
      is attributed to scattering and absorbance. Corneal endothelial cells, which line
      the back of the cornea and are more numerous in the periphery, therefore receive
      a lower dose of UV than do those in the central cornea. This is consistent with
      the recent observation that endothelial cells in the corneal periphery exhibit
      less nuclear oxidative DNA damage than those in the central cornea.

PMID- 22455909
TI  - Mechanical modulation of receptor-ligand interactions at cell-cell interfaces.
AB  - Cell surface receptors have been extensively studied because they initiate and
      regulate signal transduction cascades leading to a variety of functional cellular
      outcomes. An important class of immune receptors (e.g., T-cell antigen receptors)
      whose ligands are anchored to the surfaces of other cells remain poorly
      understood. The mechanism by which ligand binding initiates receptor
      phosphorylation, a process termed "receptor triggering", remains controversial.
      Recently, direct measurements of the (two-dimensional) receptor-ligand complex
      lifetimes at cell-cell interface were found to be smaller than (three
      dimensional) lifetimes in solution but the underlying mechanism is unknown. At
      the cell-cell interface, the receptor-ligand complex spans a short intermembrane
      distance (15 nm) compared to long surface molecules (LSMs) whose ectodomains span
      >40 nm and these LSMs include phosphatases (e.g., CD45) that dephosphorylate the
      receptor. It has been proposed that size-based segregation of LSMs from a
      receptor-ligand complex is a mechanism of receptor triggering but it is unclear
      whether the mechanochemistry supports such small-scale segregation. Here we
      present a nanometer-scale mathematical model that couples membrane elasticity
      with the compressional stiffness and lateral mobility of LSMs. We find robust
      supradiffusive segregation of LSMs from a single receptor-ligand complex. The
      model predicts that LSM redistribution will result in a time-dependent tension on
      the complex leading to a decreased two-dimensional lifetime. Interestingly, the
      model predicts a nonlinear relationship between the three- and two-dimensional
      lifetimes, which can enhance the ability of receptors to discriminate between
      similar ligands.

PMID- 22455910
TI  - Random hydrolysis controls the dynamic instability of microtubules.
AB  - Uncovering mechanisms that control the dynamics of microtubules is fundamental
      for our understanding of multiple cellular processes such as chromosome
      separation and cell motility. Building on previous theoretical work on the
      dynamic instability of microtubules, we propose here a stochastic model that
      includes all relevant biochemical processes that affect the dynamics of
      microtubule plus-end, namely, the binding of GTP-bound monomers, unbinding of GTP
      and GDP-bound monomers, and hydrolysis of GTP monomers. The inclusion of
      dissociation processes, present in our approach but absent from many previous
      studies, is essential to guarantee the thermodynamic consistency of the model.
      Our theoretical method allows us to compute all dynamic properties of
      microtubules explicitly. Using experimentally determined rates, it is found that
      the cap size is ~3.6 layers, an estimate that is compatible with several
      experimental observations. In the end, our model provides a comprehensive
      description of the dynamic instability of microtubules that includes not only the
      statistics of catastrophes but also the statistics of rescues.

PMID- 22455911
TI  - Transport phenomena in articular cartilage cryopreservation as predicted by the
      modified triphasic model and the effect of natural inhomogeneities.
AB  - Knowledge of the spatial and temporal distribution of cryoprotective agent (CPA)
      is necessary for the cryopreservation of articular cartilage. Cartilage
      dehydration and shrinkage, as well as the change in extracellular osmolality, may
      have a significant impact on chondrocyte survival during and after CPA loading,
      freezing, and thawing, and during CPA unloading. In the literature, Fick's law of
      diffusion is commonly used to predict the spatial distribution and overall
      concentration of the CPA in the cartilage matrix, and the shrinkage and stress
      strain in the cartilage matrix during CPA loading are neglected. In this study,
      we used a previously described biomechanical model to predict the spatial and
      temporal distributions of CPA during loading. We measured the intrinsic
      inhomogeneities in initial water and fixed charge densities in the cartilage
      using magnetic resonance imaging and introduced them into the model as initial
      conditions. We then compared the prediction results with the results obtained
      using uniform initial conditions. The simulation results in this study
      demonstrate the presence of a significant mechanical strain in the matrix of the
      cartilage, within all layers, during CPA loading. The osmotic response of the
      chondrocytes to the cartilage dehydration during CPA loading was also simulated.
      The results reveal that a transient shrinking occurs to different levels, and the
      chondrocytes experience a significant decrease in volume, particularly in the
      middle and deep zones of articular cartilage, during CPA loading.

PMID- 22455912
TI  - Cardiac cellular coupling and the spread of early instabilities in intracellular
      Ca2+.
AB  - Recent experimental and modeling studies demonstrate the fine spatial scale,
      complex nature, and independent contribution of Ca(2+) dynamics as a
      proarrhythmic factor in the heart. The mechanism of progression of cell-level
      Ca(2+) instabilities, known as alternans, to tissue-level arrhythmias is not well
      understood. Because gap junction coupling dictates cardiac syncytial properties,
      we set out to elucidate its role in the spatiotemporal evolution of Ca(2+)
      instabilities. We experimentally perturbed cellular coupling in cardiac syncytium
      in vitro. Coupling was quantified by fluorescence recovery after photobleaching,
      and related to function, including subtle fine-scale Ca(2+) alternans, captured
      by optical mapping. Conduction velocity and threshold for alternans monotonically
      increased with coupling. Lower coupling enhanced Ca(2+) alternans amplitude, but
      the spatial spread of early (<2 Hz) alternation was the greatest under
      intermediate (not low) coupling. This nonmonotonic relationship was closely
      matched by the percent of samples exhibiting large-scale alternans at higher
      pacing rates. Computer modeling corroborated these experimental findings for
      strong but not weak electromechanical (voltage-Ca(2+)) coupling, and offered
      mechanistic insight. In conclusion, using experimental and modeling approaches,
      we reveal a general mechanism for the spatial spread of subtle cellular Ca(2+)
      alternans that relies on a combination of gap-junctional and voltage-Ca(2+)
      coupling.

PMID- 22455913
TI  - Multiscale strain analysis of tissue equivalents using a custom-designed biaxial
      testing device.
AB  - Mechanical signals transferred between a cell and its extracellular matrix play
      an important role in regulating fundamental cell behavior. To further define the
      complex mechanical interactions between cells and matrix from a multiscale
      perspective, a biaxial testing device was designed and built. Finite element
      analysis was used to optimize the cruciform specimen geometry so that stresses
      within the central region were concentrated and homogenous while minimizing shear
      and grip effects. This system was used to apply an equibiaxial loading and
      unloading regimen to fibroblast-seeded tissue equivalents. Digital image
      correlation and spot tracking were used to calculate three-dimensional strains
      and associated strain transfer ratios at macro (construct), meso, matrix
      (collagen fibril), cell (mitochondria), and nuclear levels. At meso and matrix
      levels, strains in the 1- and 2-direction were statistically similar throughout
      the loading-unloading cycle. Interestingly, a significant amplification of
      cellular and nuclear strains was observed in the direction perpendicular to the
      cell axis. Findings indicate that strain transfer is dependent upon local
      anisotropies generated by the cell-matrix force balance. Such multiscale
      approaches to tissue mechanics will assist in advancement of modern biomechanical
      theories as well as development and optimization of preconditioning regimens for
      functional engineered tissue constructs.

PMID- 22455914
TI  - Coupling of Ci-VSP modules requires a combination of structure and electrostatics
      within the linker.
AB  - The voltage-sensitive phosphatase Ci-VSP consists of an intracellular phosphatase
      domain (PD) coupled to a transmembrane voltage-sensor domain (VSD).
      Depolarization triggers the selective dephosphorylation of phosphoinositides.
      However, the molecular mechanisms of coupling are still elusive. To clarify the
      role of the VSD-PD linker as a putative partner for electrostatic interactions
      with the membrane, we carried out a cysteine-scanning mutagenesis of the whole
      motif M240-K257. Upon coexpression with PI(4,5)P(2)-sensitive KCNQ2/KCNQ3
      channels in Xenopus oocytes, we identified four positions (A242C, R245C, K252C,
      and Y255C) with a completely abrogated PD activity. Because the mutation effect
      occurred periodically, we hypothesize that alpha-helical elements exist within
      the linker, with a gap near position S249. The combination of these results with
      the analysis of transient sensing currents of the VSD revealed distinct roles for
      the N-terminal (M240-S249) and C-terminal (Q250-K257) linker motifs in the VSD-PD
      coupling. According to our functional results, the computational structure
      prediction of the Q239-D258 fragment confirmed alpha-helical structures within
      the linker, with a short beta-turn around S249 in the activated conformation.
      Remarkably, the position K252 may be a candidate for interacting with the PD
      rather than for binding to the membrane. This provides the first insight (to our
      knowledge) into the direct intervention of the linker in the VSD-PD coupling
      process.

PMID- 22455915
TI  - Three-dimensional analysis of the effect of epidermal growth factor on cell-cell
      adhesion in epithelial cell clusters.
AB  - The effect that growth factors such as epidermal growth factor (EGF) have on cell
      cell adhesion is of interest in the study of cellular processes such as
      epithelial-mesenchymal transition. Because cell-cell adhesions cannot be measured
      directly, we use three-dimensional traction force microscopy to measure the
      tractions applied by clusters of MCF-10A cells to a compliant substrate beneath
      them before and after stimulating the cells with EGF. To better interpret the
      results, a finite element model, which simulates a cluster of individual cells
      adhered to one another and to the substrate with linear springs, is developed to
      better understand the mechanical interaction between the cells in the
      experiments. The experiments and simulations show that the cluster of cells acts
      collectively as a single unit, indicating that cell-cell adhesion remains strong
      before and after stimulation with EGF. In addition, the experiments and model
      emphasize the importance of three-dimensional measurements and analysis in these
      experiments.

PMID- 22455916
TI  - Constraints imposed by the membrane selectively guide the alternating access
      dynamics of the glutamate transporter GltPh.
AB  - Substrate transport in sodium-coupled amino acid symporters involves a large
      scale conformational change that shifts the access to the substrate-binding site
      from one side of the membrane to the other. The structural change is particularly
      substantial and entails a unique piston-like quaternary rearrangement in
      glutamate transporters, as evidenced by the difference between the outward-facing
      and inward-facing structures resolved for the archaeal aspartate transporter
      Glt(Ph). These structural changes occur over time and length scales that extend
      beyond the reach of current fully atomic models, but are regularly explored with
      the use of elastic network models (ENMs). Despite their success with other
      membrane proteins, ENM-based approaches for exploring the collective dynamics of
      Glt(Ph) have fallen short of providing a plausible mechanism. This deficiency is
      attributed here to the anisotropic constraints imposed by the membrane, which are
      not incorporated into conventional ENMs. Here we employ two novel (to our
      knowledge) ENMs to demonstrate that one can largely capture the experimentally
      observed structural change using only the few lowest-energy modes of motion that
      are intrinsically accessible to the transporter, provided that the surrounding
      lipid molecules are incorporated into the ENM. The presence of the membrane
      reduces the overall energy of the transition compared with conventional models,
      showing that the membrane not only guides the selected mechanism but also acts as
      a facilitator. Finally, we show that the dynamics of Glt(Ph) is biased toward
      transitions of individual subunits of the trimer rather than cooperative
      transitions of all three subunits simultaneously, suggesting a mechanism of
      transport that exploits the intrinsic dynamics of individual subunits. Our
      software is available online at http://www.membranm.csb.pitt.edu.

PMID- 22455917
TI  - Molecular dynamics simulations of the Cx26 hemichannel: insights into voltage
      dependent loop-gating.
AB  - Loop-gating is one of two voltage-dependent mechanisms that regulate the open
      probability of connexin channels. The loop-gate permeability barrier is formed by
      a segment of the first extracellular loop (E1) (the parahelix) and appears to be
      accompanied by straightening of the bend angle between E1 and the first
      transmembrane domain (TM1). Here, all-atom molecular dynamics simulations are
      used to identify and characterize interacting van der Waals and electrostatic
      networks that stabilize the parahelices and TM1/E1 bend angles of the open Cx26
      hemichannel. Dynamic fluctuations in an electrostatic network in each subunit are
      directly linked to the stability of parahelix structure and TM1/E1 bend angle in
      adjacent subunits. The electrostatic network includes charged residues that are
      pore-lining and thus positioned to be voltage sensors. We propose that the
      transition to the closed state is initiated by voltage-driven disruption of the
      networks that stabilize the open-state parahelix configuration, allowing the
      parahelix to protrude into the channel pore to form the loop-gate barrier.
      Straightening of the TM1/E1 bend appears to be a consequence of the
      reorganization of the interacting networks that accompany the conformational
      change of the parahelix. The electrostatic network extends across subunit
      boundaries, suggesting a concerted gating mechanism.

PMID- 22455918
TI  - Applicability of cable theory to vascular conducted responses.
AB  - Conduction processes in the vasculature have traditionally been described using
      cable theory, i.e., locally induced signals decaying passively along the
      arteriolar wall. The decay is typically quantified using the steady-state length
      constant, lambda, derived from cable theory. However, the applicability of cable
      theory to blood vessels depends on assumptions that are not necessarily fulfilled
      in small arteries and arterioles. We have employed a morphologically and
      electrophysiologically detailed mathematical model of a rat mesenteric arteriole
      to investigate if the assumptions hold and whether lambda adequately describes
      simulated conduction profiles. We find that several important cable theory
      assumptions are violated when applied to small blood vessels. However, the
      phenomenological use of a length-constant from a single exponential function is a
      good measure of conduction length. Hence, lambda should be interpreted as a
      descriptive measure and not in light of cable theory. Determination of lambda
      using cable theory assumes steady-state conditions. In contrast, using the model
      it is possible to probe how conduction behaves before steady state is achieved.
      As ion channels have time-dependent activation and inactivation, the conduction
      profile changes considerably during this dynamic period with an initially longer
      spread of current. This may have implications in relation to explaining why
      different agonists have different conduction properties. Also, it illustrates the
      necessity of using and developing models that handle the nonlinearity of ion
      channels.

PMID- 22455919
TI  - Molecular dynamics investigation of Cl- and water transport through a eukaryotic
      CLC transporter.
AB  - Early crystal structures of prokaryotic CLC proteins identified three Cl(-)
      binding sites: internal (S(int)), central (S(cen)), and external (S(ext)). A
      conserved external GLU (GLU(ex)) residue acts as a gate competing for S(ext).
      Recently, the first crystal structure of a eukaryotic transporter, CmCLC,
      revealed that in this transporter GLU(ex) competes instead for S(cen). Here, we
      use molecular dynamics simulations to investigate Cl(-) transport through CmCLC.
      The gating and Cl(-)/H(+) transport cycle are inferred through comparative
      molecular dynamics simulations with protonated and deprotonated GLU(ex) in the
      presence/absence of external potentials. Adaptive biasing force calculations are
      employed to estimate the potential of mean force profiles associated with
      transport of a Cl(-) ion from S(ext) to S(int), depending on the Cl(-) occupancy
      of other sites. Our simulations demonstrate that protonation of GLU(ex) is
      essential for Cl(-) transport from S(ext) to S(cen). The S(cen) site may be
      occupied by two Cl(-) ions simultaneously due to a high energy barrier (~8
      Kcal/mol) for a single Cl(-) ion to translocate from S(cen) to S(int). Binding
      two Cl(-) ions to S(cen) induces a continuous water wire from S(cen) to the
      extracellular solution through the side chain of the GLU(ex) gate. This may
      initiate deprotonation of GLU(ex), which then drives the two Cl(-) ions out of
      S(cen) toward the intracellular side via two putative Cl(-) transport paths.
      Finally, a conformational cycle is proposed that would account for the exchange
      stoichiometry.

PMID- 22455920
TI  - Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations
      in the voltage-sensing domain.
AB  - Changes in voltage-dependent gating represent a common pathogenetic mechanism for
      genetically inherited channelopathies, such as benign familial neonatal seizures
      or peripheral nerve hyperexcitability caused by mutations in neuronal K(v)7.2
      channels. Mutation-induced changes in channel voltage dependence are most often
      inferred from macroscopic current measurements, a technique unable to provide a
      detailed assessment of the structural rearrangements underlying channel gating
      behavior; by contrast, gating currents directly measure voltage-sensor
      displacement during voltage-dependent gating. In this work, we describe
      macroscopic and gating current measurements, together with molecular modeling and
      molecular-dynamics simulations, from channels carrying mutations responsible for
      benign familial neonatal seizures and/or peripheral nerve hyperexcitability;
      K(v)7.4 channels, highly related to K(v)7.2 channels both functionally and
      structurally, were used for these experiments. The data obtained showed that
      mutations affecting charged residues located in the more distal portion of S(4)
      decrease the stability of the open state and the active voltage-sensing domain
      configuration but do not directly participate in voltage sensing, whereas
      mutations affecting a residue (R4) located more proximally in S(4) caused
      activation of gating-pore currents at depolarized potentials. These results
      reveal that distinct molecular mechanisms underlie the altered gating behavior of
      channels carrying disease-causing mutations at different voltage-sensing domain
      locations, thereby expanding our current view of the pathogenesis of neuronal
      hyperexcitability diseases.

PMID- 22455921
TI  - P-glycoprotein-ATPase modulation: the molecular mechanisms.
AB  - P-glycoprotein-ATPase is an efflux transporter of broad specificity that
      counteracts passive allocrit influx. Understanding the rate of allocrit transport
      therefore matters. Generally, the rates of allocrit transport and ATP hydrolysis
      decrease exponentially with increasing allocrit affinity to the transporter. Here
      we report unexpectedly strong down-modulation of the P-glycoprotein-ATPase by
      certain detergents. To elucidate the underlying mechanism, we chose 34
      electrically neutral and cationic detergents with different hydrophobic and
      hydrophilic characteristics. Measurement of the P-glycoprotein-ATPase activity as
      a function of concentration showed that seven detergents activated the ATPase as
      expected, whereas 27 closely related detergents reduced it significantly.
      Assessment of the free energy of detergent partitioning into the lipid membrane
      and the free energy of detergent binding from the membrane to the transporter
      revealed that the ratio, q, of the two free energies of binding determined the
      rate of ATP hydrolysis. Neutral (cationic) detergents with a ratio of q = 2.7 +/-
      0.2 (q > 3) followed the aforementioned exponential dependence. Small deviations
      from the optimal ratio strongly reduced the rates of ATP hydrolysis and flopping,
      respectively, whereas larger deviations led to an absence of interaction with the
      transporter. P-glycoprotein-ATPase inhibition due to membrane disordering by
      detergents could be fully excluded using (2)H-NMR-spectroscopy. Similar
      principles apply to modulating drugs.

PMID- 22455922
TI  - Measuring Ca2+-induced structural changes in lipid monolayers: implications for
      synaptic vesicle exocytosis.
AB  - Synaptic vesicles (SVs) are small, membrane-bound organelles that are found in
      the synaptic terminal of neurons. Although tremendous progress has been made in
      understanding the protein machinery that drives fusion of SVs with the
      presynaptic membrane, little progress has been made in understanding changes in
      the membrane structure that accompany this process. We used lipid monolayers of
      defined composition to mimic biological membranes, which were probed by x-ray
      reflectivity and grazing incidence x-ray diffraction. These techniques allowed us
      to successfully monitor structural changes in the membranes at molecular level,
      both in response to injection of SVs in the subphase below the monolayer, as well
      as to physiological cues involved in neurotransmitter release, such as increases
      in the concentration of the membrane lipid PIP(2), or addition of physiological
      levels of Ca(2+). Such structural changes may well modulate vesicle fusion in
      vivo.

PMID- 22455923
TI  - Determining the Gaussian curvature modulus of lipid membranes in simulations.
AB  - The Gaussian curvature modulus kappa- of lipid bilayers likely contributes more
      than 100 kcal/mol to every cellular fission or fusion event. This huge impact on
      membrane remodeling energetics might be a factor that codetermines the complex
      lipid composition of biomembranes through tuning of kappa-. Yet, its value has
      been measured only for a handful of simple lipids, and no simulation has so far
      determined it better than a factor of two, rendering a systematic investigation
      of such enticing speculations impossible. Here we propose a highly accurate
      method to determine kappa- in computer simulations. It relies on the interplay
      between curvature stress and edge tension of partially curved axisymmetric
      membrane disks and requires determining their closing probability. For a
      simplified lipid model we obtain kappa- and its relation to the normal bending
      modulus kappa for membranes differing both in stiffness and spontaneous lipid
      curvature. The elastic ratio kappa-/kappa can be determined with a few percent
      statistical accuracy. Its value agrees with the scarce experimental data, and its
      change with spontaneous lipid curvature is compatible with theoretical
      expectations, thereby granting additional information on monolayer properties. We
      also show that an alternative determination of these elastic parameters based on
      moments of the lateral stress profile gives markedly different and unphysical
      values.

PMID- 22455924
TI  - The amyloid precursor protein forms plasmalemmal clusters via its pathogenic
      amyloid-beta domain.
AB  - The amyloid precursor protein (APP) is a large, ubiquitous integral membrane
      protein with a small amyloid-beta (Abeta) domain. In the human brain, endosomal
      processing of APP produces neurotoxic Abeta-peptides, which are involved in
      Alzheimer's disease. Here, we show that the Abeta sequence exerts a physiological
      function when still present in the unprocessed APP molecule. From the
      extracellular site, Abeta concentrates APP molecules into plasmalemmal membrane
      protein clusters. Moreover, Abeta stabilization of clusters is a prerequisite for
      their targeting to endocytic clathrin structures. Therefore, we conclude that the
      Abeta domain directly mediates a central step in APP trafficking, driving its own
      conversion into neurotoxic peptides.

PMID- 22455926
TI  - Nanopore detachment kinetics of poly(A) binding proteins from RNA molecules
      reveals the critical role of C-terminus interactions.
AB  - The ubiquitous and abundant cytoplasmic poly(A) binding protein (PABP) is a
      highly conserved multifunctional protein, many copies of which bind to the
      poly(A) tail of eukaryotic mRNAs to promote translation initiation. The N
      terminus of PABP is responsible for the high binding specificity and affinity to
      poly(A), whereas the C-terminus is known to stimulate PABP multimerization on
      poly(A). Here, we use single-molecule nanopore force spectroscopy to directly
      measure interactions between poly(A) and PABPs. Both electrical and biochemical
      results show that the C-C domain interaction between two consecutive PABPs
      promotes cooperative binding. Up to now, investigators have not been able to
      probe the detailed polarity configuration (i.e., the internal arrangement of two
      PABPs on a poly(A) streak in which the C-termini face toward or away from each
      other). Our nanopore force spectroscopy system is able to distinguish the
      cooperative binding conformation from the noncooperative one. The ~50%
      cooperative binding conformation of wild-type PABPs indicates that the C-C domain
      interaction doubles the cooperative binding probability. Moreover, the longer
      dissociation time of a cooperatively bound poly(A)/PABP complex as compared with
      a noncooperatively bound one indicates that the cooperative mode is the most
      stable conformation for PABPs binding onto the poly(A). However, ~50% of the
      poly(A)/PABP complexes exhibit a noncooperative binding conformation, which is in
      line with previous studies showing that the PABP C-terminal domain also interacts
      with additional protein cofactors.

PMID- 22455925
TI  - Orientation of the N-terminal lobe of the myosin regulatory light chain in
      skeletal muscle fibers.
AB  - The orientation of the N-terminal lobe of the myosin regulatory light chain (RLC)
      in demembranated fibers of rabbit psoas muscle was determined by polarized
      fluorescence. The native RLC was replaced by a smooth muscle RLC with a
      bifunctional rhodamine probe attached to its A, B, C, or D helix. Fiber
      fluorescence data were interpreted using the crystal structure of the head domain
      of chicken skeletal myosin in the nucleotide-free state. The peak angle between
      the lever axis of the myosin head and the fiber or actin filament axis was 100
      110 degrees  in relaxation, isometric contraction, and rigor. In each state the
      hook helix was at an angle of ~40 degrees  to the lever/filament plane. The in
      situ orientation of the RLC D and E helices, and by implication of its N- and C
      lobes, was similar in smooth and skeletal RLC isoforms. The angle between these
      two RLC lobes in rigor fibers was different from that in the crystal structure.
      These results extend previous crystallographic evidence for bending between the
      two lobes of the RLC to actin-attached myosin heads in muscle fibers, and suggest
      that such bending may have functional significance in contraction and regulation
      of vertebrate striated muscle.

PMID- 22455927
TI  - Dimerization of helical beta-peptides in solution.
AB  - Molecular simulations are used to examine the aggregation behavior of several
      beta-peptides in explicit water. The particular peptides considered here adopt a
      helical, rodlike conformation in aqueous solution. Four distinct molecular
      sequences are considered. Earlier experimental studies have revealed the
      formation of ordered and disordered aggregates for such molecules, depending on
      sequence. The simulations reported here, which are conducted by resorting to
      metadynamics techniques, lead to free energy surfaces for dimerization of the
      peptides in water as a function of separation and relative orientation. Such
      surfaces are used to identify the molecular origins for the behaviors observed in
      the experiments.

PMID- 22455928
TI  - Sequence-dependent stability test of a left-handed beta-helix motif.
AB  - The left-handed beta-helix (LHBH) is an intriguing, rare structural pattern in
      polypeptides that has been implicated in the formation of amyloid aggregates. We
      used accurate all-atom replica-exchange molecular dynamics (REMD) simulations to
      study the relative stability of diverse sequences in the LHBH conformation.
      Ensemble-average coordinates from REMD served as a scoring criterion to identify
      sequences and threadings optimally suited to the LHBH, as in a fold recognition
      paradigm. We examined the repeatability of our REMD simulations, finding that
      single simulations can be reliable to a quantifiable extent. We find expected
      behavior for the positive and negative control cases of a native LHBH and
      intrinsically disordered sequences, respectively. Polyglutamine and a designed
      hexapeptide repeat show remarkable affinity for the LHBH motif. A structural
      model for misfolded murine prion protein was also considered, and showed
      intermediate stability under the given conditions. Our technique is found to be
      an effective probe of LHBH stability, and promises to be scalable to broader
      studies of this and potentially other novel or rare motifs. The superstable
      character of the designed hexapeptide repeat suggests theoretical and
      experimental follow-ups.

PMID- 22455929
TI  - Free-energy simulations reveal that both hydrophobic and polar interactions are
      important for influenza hemagglutinin antibody binding.
AB  - Antibodies binding to conserved epitopes can provide a broad range of
      neutralization to existing influenza subtypes and may also prevent the
      propagation of potential pandemic viruses by fighting against emerging strands.
      Here we propose a computational framework to study structural binding patterns
      and detailed molecular mechanisms of viral surface glycoprotein hemagglutinin
      (HA) binding with a broad spectrum of neutralizing monoclonal antibody fragments
      (Fab). We used rigorous free-energy perturbation (FEP) methods to calculate the
      antigen-antibody binding affinities, with an aggregate underlying molecular
      dynamics simulation time of several microseconds (~2 MUs) using all-atom,
      explicit-solvent models. We achieved a high accuracy in the validation of our FEP
      protocol against a series of known binding affinities for this complex system,
      with <0.5 kcal/mol errors on average. We then introduced what to our knowledge
      are novel mutations into the interfacial region to further study the binding
      mechanism. We found that the stacking interaction between Trp-21 in HA2 and Phe
      55 in the CDR-H2 of Fab is crucial to the antibody-antigen association. A single
      mutation of either W21A or F55A can cause a binding affinity decrease of
      DeltaDeltaG > 4.0 kcal/mol (equivalent to an ~1000-fold increase in the
      dissociation constant K(d)). Moreover, for group 1 HA subtypes (which include
      both the H1N1 swine flu and the H5N1 bird flu), the relative binding affinities
      change only slightly (< +/-1 kcal/mol) when nonpolar residues at the alphaA helix
      of HA mutate to conservative amino acids of similar size, which explains the
      broad neutralization capability of antibodies such as F10 and CR6261. Finally, we
      found that the hydrogen-bonding network between His-38 (in HA1) and Ser-30/Gln-64
      (in Fab) is important for preserving the strong binding of Fab against group 1
      HAs, whereas the lack of such hydrogen bonds with Asn-38 in most group 2 HAs may
      be responsible for the escape of antibody neutralization. These large-scale
      simulations may provide new insight into the antigen-antibody binding mechanism
      at the atomic level, which could be essential for designing more-effective
      vaccines for influenza.

PMID- 22455930
TI  - Residue-specific alpha-helix propensities from molecular simulation.
AB  - Formation of alpha-helices is a fundamental process in protein folding and
      assembly. By studying helix formation in molecular simulations of a series of
      alanine-based peptides, we obtain the temperature-dependent alpha-helix
      propensities of all 20 naturally occurring residues with two recent additive
      force fields, Amber ff03w and Amber ff99SB(*). Encouragingly, we find that the
      overall helix propensity of many residues is captured well by both energy
      functions, with Amber ff99SB(*) being more accurate. Nonetheless, there are some
      residues that deviate considerably from experiment, which can be attributed to
      two aspects of the energy function: i), variations of the charge model used to
      determine the atomic partial charges, with residues whose backbone charges differ
      most from alanine tending to have the largest error; ii), side-chain torsion
      potentials, as illustrated by the effect of modifications to the torsion angles
      of I, L, D, N. We find that constrained refitting of residue charges for charged
      residues in Amber ff99SB(*) significantly improves their helix propensity. The
      resulting parameters should more faithfully reproduce helix propensities in
      simulations of protein folding and disordered proteins.

PMID- 22455931
TI  - Kinetic schemes for post-synchronized single molecule dynamics.
AB  - Recordings from single molecule experiments can be aggregated to determine
      average kinetic properties of the system under observation. The kinetics after a
      synchronized reaction step can be interpreted using all of the standard tools
      developed for ensemble perturbation experiments. The kinetics leading up to a
      synchronized event, determined by the lifetimes of the preceding states; however,
      are not as obvious if the reaction has reversible steps or branches. Here we
      describe a general procedure for dealing with these situations.

PMID- 22455932
TI  - Musca domestica pupae lectin induces apoptosis in HepG2 cells through a NF
      kappaB/p65-mediated caspase pathway.
AB  - A new lectin (42 kDa) from Musca domestica pupae (MPL) has been known to inhibit
      proliferation in tumor cells. In this study, flow cytometry analysis showed that
      MPL induced HepG2 cells apoptosis significantly and the cells were arrested at S
      phase. MPL inhibited IkappaB-alpha degradation and NF-kappaB/p65 translocation
      from cytoplasm into nucleus. Simultaneously, the expressions of FLIP, which is a
      target gene of NF-kappaB/p65 were down-regulated and the caspase-8 and caspase-3
      were then activated to induce apoptosis. Taken together, these results showed
      that MPL induced a caspase-dependent apoptosis via NF-kappaB/p65 pathway in HepG2
      cells.

PMID- 22455933
TI  - Usage of skin care products and risk of rheumatoid arthritis: results from the
      Swedish EIRA study.
AB  - INTRODUCTION: The aim of this study was to investigate the association between
      exposure to cosmetics, often containing mineral oil, and the risk of developing
      rheumatoid arthritis (RA). The study was performed against the background that
      occupational exposure to mineral oil has recently been shown to be associated
      with an increased risk for RA in man, and that injection of or percutaneous
      exposure to mineral-oil-containing cosmetics can induce arthritis in certain rat
      strains. METHODS: A population-based case-control study of incident cases of RA
      was performed among the population aged 18 to 70 years in a defined area of
      Sweden during May 1996 to December 2003. A case was defined as an individual from
      the study base, who received for the first time a diagnosis of RA according to
      the 1987 American College of Rheumatology criteria. Controls were randomly
      selected from the study base with consideration taken for age, gender and
      residential area. Cases (n = 1,419) and controls (n = 1,674) answered an
      extensive questionnaire regarding environmental and lifestyle factors including
      habits of cosmetic usage. The relative risk of developing RA was calculated for
      subjects with different cosmetic usage compared with subjects with low or no
      usage. Analysis was also performed stratifying the cases for presence/absence of
      rheumatoid factor and antibodies to citrulline-containing peptides. RESULTS: The
      relative risks of developing RA associated with use of cosmetics were all close
      to one, both for women and men, for different exposure categories, and in
      relation to different subgroups of RA. CONCLUSION: This study does not support
      the hypothesis that ordinary usage of common cosmetics as body lotions, skin
      creams, and ointments, often containing mineral oil, increase the risk for RA in
      the population in general. We cannot exclude, however, that these cosmetics can
      contribute to arthritis in individuals carrying certain genotypes or
      simultaneously being exposed to other arthritis-inducing environmental agents.

PMID- 22455934
TI  - Comparison on genomic predictions using three GBLUP methods and two single-step
      blending methods in the Nordic Holstein population.
AB  - BACKGROUND: A single-step blending approach allows genomic prediction using
      information of genotyped and non-genotyped animals simultaneously. However, the
      combined relationship matrix in a single-step method may need to be adjusted
      because marker-based and pedigree-based relationship matrices may not be on the
      same scale. The same may apply when a GBLUP model includes both genomic breeding
      values and residual polygenic effects. The objective of this study was to compare
      single-step blending methods and GBLUP methods with and without adjustment of the
      genomic relationship matrix for genomic prediction of 16 traits in the Nordic
      Holstein population. METHODS: The data consisted of de-regressed proofs (DRP) for
      5,214 genotyped and 9,374 non-genotyped bulls. The bulls were divided into a
      training and a validation population by birth date, October 1, 2001. Five
      approaches for genomic prediction were used: 1) a simple GBLUP method, 2) a GBLUP
      method with a polygenic effect, 3) an adjusted GBLUP method with a polygenic
      effect, 4) a single-step blending method, and 5) an adjusted single-step blending
      method. In the adjusted GBLUP and single-step methods, the genomic relationship
      matrix was adjusted for the difference of scale between the genomic and the
      pedigree relationship matrices. A set of weights on the pedigree relationship
      matrix (ranging from 0.05 to 0.40) was used to build the combined relationship
      matrix in the single-step blending method and the GBLUP method with a polygenetic
      effect. RESULTS: Averaged over the 16 traits, reliabilities of genomic breeding
      values predicted using the GBLUP method with a polygenic effect (relative weight
      of 0.20) were 0.3% higher than reliabilities from the simple GBLUP method
      (without a polygenic effect). The adjusted single-step blending and original
      single-step blending methods (relative weight of 0.20) had average reliabilities
      that were 2.1% and 1.8% higher than the simple GBLUP method, respectively. In
      addition, the GBLUP method with a polygenic effect led to less bias of genomic
      predictions than the simple GBLUP method, and both single-step blending methods
      yielded less bias of predictions than all GBLUP methods. CONCLUSIONS: The single
      step blending method is an appealing approach for practical genomic prediction in
      dairy cattle. Genomic prediction from the single-step blending method can be
      improved by adjusting the scale of the genomic relationship matrix.

PMID- 22455936
TI  - [To further standardize the diagnosis and treatment of obstructive sleep apnea
      hypopnea syndrome].

PMID- 22455935
TI  - Clinical observations with Closed Loop Stimulation pacemakers in a large patient
      cohort: the CYLOS routine documentation registry (RECORD).
AB  - AIMS: Closed Loop Stimulation (CLS) pacemakers couple pacing rate to myocardial
      contraction dynamics by monitoring unipolar right ventricular impedance on a beat
      to-beat basis. The aim of this large-scale registry was to evaluate the safety
      and efficacy of the CLS therapy under clinical routine conditions. METHODS AND
      RESULTS: A total of 706 patients was enrolled in the clinical investigation
      'Registry: CYLOS Routine Documentation' (RECORD) at 57 investigational sites in
      Europe and Hong Kong. Not to interfere with clinical routine and therapeutic
      decisions of health care providers, the registry was implemented as a part of the
      standard follow-up schedule. Two follow-ups were conducted within 12 months of
      enrolment in order to evaluate typical programming of CLS-related parameters,
      reasons for their later reprogramming, frequency of patient intolerance to CLS,
      and physicians' satisfaction with medical benefits and technical performance of
      CLS in each patient. The investigators' medical and technical notes on CLS rated
      it excellent in ~80% of patients, poor in 1.4% (medical benefit) or 0.5%
      (technical performance), and adequate in rest of the patients. Closed Loop
      Stimulation functionality was not influenced by pacing site variation within the
      right ventricle (septal, outflow tract) or by advanced heart failure (New York
      Heart Association classes II-IV). Permanent or temporary CLS deactivation was
      undertaken for various reasons in 6.2% of patients. Signs of intolerance to CLS
      or rate-adaptive pacing were reported by 2.3% of patients. Reprogramming of CLS
      related parameters was seldom undertaken, with >90% of pacemakers operating with
      default settings in the long term. CONCLUSION: Clinical performance of CLS was
      very satisfactory in the large cohort studied.

PMID- 22455937
TI  - [The interpretation of the guideline of obstructive sleep apnea hypopnea
      syndrome].

PMID- 22455938
TI  - [The relation of learning deficits with oxidative stress in rats exposed to
      severe intermittent hypoxia].
AB  - OBJECTIVE: To observe the relations between learning memory function and
      oxidative stress in rats exposed to severe intermittent hypoxia (IH). METHODS:
      Adult male Wistar rats (n = 48) were randomly assigned to 2 groups: untreated
      control group (UC) and 5% intermittent hypoxia group (5%IH). At 2, 4, 6 and 8
      weeks, the learning and memory ability of the rats in each group were assessed
      with the Morris water maze (MWM) test. The ultrastructural changes in the
      hippocampus of the rats were observed with transmission electron microscopy
      (TEM). The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were
      detected by colorimetric method. RESULTS: The water maze test showed that the
      rats in the 5% IH group had prolonged latency in escaping, reduced target
      quadrant time in crossing and reduced frequency of crossing the platform, as
      compared to the UC group (P < 0.05). With longer time of hypoxia, the damage
      became more significant. It was observed that the structure of neuron cell was
      complete and organelles were abundant in UC groups. With the extension of
      exposure time, the number of hippocampus neurons and synaptic were decreased in
      5%IH groups, nucleus shrank, synaptic frame became indefinite and synaptic cleft
      widen. Comparing with control group, the level of MDA in the hippocampal region
      group was significantly higher (P < 0.05) and the activity of SOD significantly
      was lower (P < 0.05) in 5%IH, along with the time expand, which aggravated.
      CONCLUSION: Severe intermittent hypoxia that results in learning and memory
      dysfunction. It is possible that oxidative stress change the quantity and
      structure of hippocampal neurons and synaptic, which aggravates along with the
      intermittent low oxygen time expand.

PMID- 22455939
TI  - [The effects of chronic intermittent hypoxia on blood pressure and sympathetic
      nerve activity in rats].
AB  - OBJECTIVE: To observe the changes of blood pressure and sympathetic nerve
      activity under different degrees of chronic intermittent hypoxia (CIH) in rats,
      and therefore to explore the effects of CIH on blood pressure and sympathetic
      nerve activity and the correlation between blood pressure and sympathetic nerve
      activity in the pathogenesis of CIH-induced hypertension. METHODS: Male Wistar
      rats (n = 168) were randomly divided into untreated group (UD), severe
      intermittent hypoxia group (IH(1)), moderate intermittent hypoxia group (IH(2)),
      mild intermittent hypoxia group (IH(3)), continuous hypoxia group (CH), sham
      control group (SC) and were exposed to different conditions. Rats (n = 8) of the
      UD group were sacrificed before the experiment, while rats of the other groups
      were killed in weeks 2, 4, 6, and 8 of the experiment. Anticoagulated venous
      blood was obtained and plasma was stored at -80 degrees C. Systolic arterial
      pressure (SBP) was recorded before and after the experiment, while plasma
      norepinephrine (NE) was measured after the experiment. RESULTS: Before the
      experiment, the SBP of rats showed no significant differences among groups (F =
      0.008, P > 0.05), but the SBP of rats in the intermittent hypoxia groups
      increased gradually, and higher than the UD group, the SC group and the CH group
      from the beginning of week 4 (P < 0.05 or P < 0.01). The blood pressure was
      positively related with the degree of hypoxia (F = 9.844, P < 0.01), and that of
      the IH(1) group was significantly higher than that of the IH(3) group (P < 0.05),
      while no significant changes were found in the SC and the CH groups. The plasma
      NE level of rats in the intermittent hypoxia groups increased gradually with the
      experiment and significantly higher than that of the UD group, the SC group and
      the CH group at week 8 (P < 0.05 or P < 0.01), and the level of NE was positively
      related with the degree of hypoxia (F = 11.537, P < 0.01). The NE level of the
      IH(1) group was significantly higher than that of the IH(3) group (P < 0.05), but
      no significant change was found in the SC and the CH groups. The plasma NE levels
      were positively related with blood pressure (r = 0.530, P < 0.01). CONCLUSIONS:
      CIH can cause increased blood pressure and sympathetic activity in rats, and the
      effect was dependent on the degree of hypoxia and the time of exposure. The
      results suggested that CIH-induced higher blood pressure was associated with
      increased sympathetic activity.

PMID- 22455940
TI  - [Effects of different patterns of hypoxia on renin angiotension system in serum
      and tissues of rats].
AB  - OBJECTIVE: To Investigate the influences of chronic intermittent hypoxia (CIH)
      and continuous hypoxia (CH) on renin angiotensin system (RAS) in serum and
      tissues of rats, and therefore to investigate the mechanism of CIH-induced
      hypertension and hypoxia induced pulmonary hypertension. METHODS: Eighteen male
      Sprague-Dawley (SD) rats were divided into 3 groups: CIH group, CH group and
      control group (UC). CIH rats were subjected to alternating cycles of hypoxia (6%
      ~ 8% O(2) in N(2) for 20 ~ 25 s) and normoxia (21% O(2) in N(2) for 2 min) every
      180 s for 7 h/d. CH rats were consistently given nitrogen (oxygen concentration
      8% - 12% in the cabin, 7 h/d), while the UC rats were not treated. RESULTS:
      Systolic blood pressure (SBP) in the CIH rats at the end of 6th week was
      significantly elevated compared with baseline SBP (P < 0.001), and that in the CH
      and the UC rats (P < 0.05). At the end of 6th week, the expression of ACE and
      ACE2 in the renal arteriole was significantly different (P < 0.05), and the
      levels of AngII in serum and kidney tissues were increased. Ang-(1-7) was
      decreased in the CIH rats compared with the CH and the UC rats (P < 0.05). The
      levels of AngII in pulmonary tissues were increased, while the levels of Ang-(1
      7) were decreased in the CH rats compared with the CIH and the UC rats (P <
      0.05). SBP showed a positive correlation with AngII in serum and kidney tissues,
      and a negative correlation with Ang-(1-7) in serum and kidney tissues. There were
      significant differences in arterial wall thickness, WT%, and WA% of renal
      arterioles and pulmonary arterioles among the 3 groups. Wall thickness of
      pulmonary arterioles and kidney arterioles was positively correlated with AngII
      in pulmonary and kidney tissues (r = 0.386, 0.414, P < 0.05), and negatively
      correlated with Ang-(1-7) (r = -0.401, -0.394, P < 0.05). CONCLUSION: CIH and CH
      showed different effects on RAS in the serum and the tissues of rats. CIH mainly
      affected levels of RAS in the serum, kidney tissues and renal arterioles, and was
      closely related with blood pressure. CH mainly affected the levels of RAS in lung
      tissues and pulmonary small arteries, which may be related with pulmonary,
      hypertension and pulmonary arterial remodeling.

PMID- 22455941
TI  - [A clinical analysis of 7 cases of allergic bronchopulmonary aspergillosis].
AB  - OBJECTIVE: To study the clinical features, diagnosis and treatment of allergic
      bronchopulmonary aspergillosis (ABPA). METHODS: The clinical presentations,
      serologic results, chest radiology, pathological results and treatment of 7
      patients with ABPA in Chinese PLA General Hospital were retrospectively analyzed.
      RESULTS: There were 4 males and 3 females, with a mean age of (33 +/- 16) years.
      Before the diagnosis of ABPA, 6 cases had been misdiagnosed as bronchial asthma,
      3 as pulmonary infection, 2 as tuberculosis and 1 as bronchiectasis. The main
      clinical manifestations included cough (n = 6), sputum production (n = 5),
      hemoptysis (n = 4), wheeze (n = 3), dyspnea(n = 3) and fever(n = 2). All cases
      had increased total serum IgE levels (median 3040 U/ml) and peripheral blood
      eosinophil count (median 0.19). Six of them showed increased peripheral
      eosinophil count median 1.84 * 10(9)/L, and skin test positive for Aspergillus
      antigen. Five of them had increased serum IgE antibodies specific to A. fumigatus
      (22 +/- 15) kU/L, and 4 had increased serum IgG antibodies specific to A.
      fumigatus (108 +/- 96) mg/L. The chest CT scan findings included transient or
      fixed pulmonary opacities, central bronchiectasis and finger-in-glove opacities.
      Five patients were treated with corticosteroids combined with antifungal therapy.
      CONCLUSIONS: Clinical features of ABPA include a history of asthma, elevation of
      the total serum IgE levels, presence of aspergillus IgE antibodies, peripheral
      eosinophilia, and transient or fixed pulmonary opacities and central
      bronchiectasis. Patients with asthma complicated with bronchiectasis should be
      routinely screened for Aspergillus skin test, and measurement of total serum IgE
      levels and chest CT scan are useful for confirmation of the diagnosis of ABPA.
      Oral glucocorticoids and anti-fungal drugs are effective in treatment of ABPA.
      Regular follow-up is needed for prevention of recurrence.

PMID- 22455942
TI  - [The evaluation of combined CT pulmonary and bronchial arteriography for the
      diagnosis of hemoptysis].
AB  - OBJECTIVE: To establish the method of multi-slice spiral CT pulmonary angiography
      (CTPA)combined with bronchial angiography (CTBA) and to evaluate its value for
      diagnosis and treatment in hemoptysis. METHODS: After contrast material was
      administered intravenously, a 16-detector row helical CT scanner (Light Speed
      Ultra 16; GE Medical Systems) was used to complete CTPA first with a scan delay
      time of 12 - 16 s. Then CTBA was carried out, with a scan delay time of 26 - 28
      s. The images were reformatted to evaluate the pulmonary artery and bronchial
      artery (BA). RESULTS: In 36 cases of hemoptysis, CTPA showed 7 pulmonary arterial
      abnormalities (3 cases with pulmonary embolism, 4 cases with one of pulmonary
      artery abnormity, primary pulmonary artery leiomyosarcoma, loss of sharpness of
      pulmonary artery or occlusion of right-inferior lung artery). In the 36 cases,
      CTBA showed 37 right BAs (11 tortuosity and thickening), 40 left right BAs (10
      tortuosity and thickening) and 3 non-bronchial systemic arteries (1 from
      abdominal aorta tortuosity and thickening). Abnormal vessels had a close relation
      with pulmonary diseases. CONCLUSIONS: With this method CTPA and CTBA can be
      completed in a single procedure and abnormal pulmonary arteries and bronchial
      arteries can be shown clearly. This procedure maybe of important value for the
      diagnosis and treatment of hemoptysis.

PMID- 22455943
TI  - [Clinical analysis of 25 cases of allergic granulomatous vasculitis].
AB  - OBJECTIVE: To improve the understanding of allergic granulomatous vasculitis,
      also called Churg-Strauss syndrome (CSS). METHODS: The clinical data, including
      clinical manifestations, laboratory findings, and pathology, of 25 patients with
      CSS were retrospectively investigated. RESULTS: There were 15 males and 10
      females, aging 18 to 72 years (mean 45 +/- 16). The clinical manifestations of
      CSS featured involvement of multiple systems or organs including respiratory
      system, nervous system, skin, digestive system, heart, and kidney. Eighty percent
      (20/25) of CSS patients had asthma as their first symptom, whereas 96.0% (24/25)
      had asthma in the whole course of CSS. The involvement of nasosinusitis of CSS
      was multi-group and the maxillary sinuses were the most frequently involved,
      which accounted for 61.1% (11/18). The peripheral nerves were involved in 72.7%
      (16/22) of patients and the most common manifestation was cerebrovascular event.
      Skin disease occurred in 60.0% (15/25), whereas heart involvement in 48.0%
      (12/25), renal involvement in 48.0% (12/25) and digestive system involvement in
      32.0% (8/25) of the patients. The positive rate of IgE was 90.0% (18/20), and
      that of ANCA was 32.0% (8/25), with P-ANCA as the predominant. The main
      presentation of chest CT scan was patchy infiltration, mostly bilateral, which
      amounted for 71.4% (15/21). The change in electromyography was mononeuritis
      multiplex, of which the peroneal nerves and popliteal nerves were the most
      frequently involved. Electrocardiography of the CSS patients was always normal
      whereas the echocardiograms showed abnormal finds in 70.0% (14/20) of the
      patients. The pathological manifestations were necrotizing vasculitis,
      eosinophilic tissue infiltration, and extravascular granulomas. CONCLUSION: The
      clinical manifestations of CSS are diverse and complex, with a lack of
      pathognomonic symptoms. Clinical manifestations, auxiliary examinations and
      pathology are often required to make a diagnosis. Early diagnosis and treatment
      will be helpful for a better prognosis.

PMID- 22455944
TI  - [Effect of STAT5 gene silencing on the proliferation of T lymphocytes in a mouse
      model of asthma].
AB  - OBJECTIVE: To study the effect of silencing STAT5 gene on the proliferation of T
      lymphocytes in a mouse model of asthma. METHODS: Spleen T-lymphocytes of normal
      and asthmatic mice were selected by immunomagnetic beads, and the STAT5a/b genes
      of these T-lymphocytes were silenced by siRNA. The mRNA of STAT5a/b was detected
      by fluorescence quantitative PCR, and the protein by Western blot. The
      proliferation rates of T-lymphocytes was evaluated by CCK-8, and the cell cycle
      and the cell apoptosis was measured by flow cytometry. RESULTS: (1) Significant
      inflammatory cell infiltration was present in asthmatic mouse airways, as
      compared to the normal control mice. (2) The STAT5a/b mRNA expression of the
      asthmatic group was significantly higher compared with the normal control group.
      (3) Compared to the blank control group, the mRNA expression of STAT5a/b was
      reduced in the siRNA-specific intervention (T: 35.014 vs 14.553, P < 0.01). The
      protein expression of STAT5a/b was also reduced after siRNA-specific intervention
      (T: -10.958 vs -14.706, P < 0.01). The proliferation rates of T lymphocytes was
      reduced after siRNA-specific intervention (T: 8.692 vs 10.540, P < 0.01), and the
      number of T-lymphocytes in proliferative phase was all significantly reduced
      after siRNA-specific intervention (T: 6.975 vs -5.567, P < 0.05). The apoptosis
      rates of T lymphocytes were significantly increased after siRNA-specific
      intervention (T: -6.404 vs -6.038, P < 0.05). CONCLUSION: RNA interference
      specifically reduced the expression of STAT5a/b, inhibited the proliferation of T
      lymphocytes, and promoted the apoptosis of T lymphocytes in a mouse model of
      asthma.

PMID- 22455945
TI  - [Changes of CD(4)(+)Foxp3(+) regulatory T cells and CD(4)(+)IL-17(+)T cells in
      cigarette smoke-exposed rats].
AB  - OBJECTIVE: To evaluate the changes of CD(4)(+)IL-17(+) T (Th17) and
      CD(4)(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood and
      bronchoalveolar lavage fluid (BALF), and therefore to explore the role of Th17
      and Treg in cigarette smoke-induced airway inflammation/COPD in rats. METHODS:
      Forty male Wistar rats were randomly divided into 4 groups: a 12 wk smoke
      exposure group, a 24 wk smoke-exposure group, a 12 wk control group and a 24 wk
      control group (n = 10 each). Cells in BALF were collected and analyzed by
      absolute and differential cell counts. IL-17 and IL-6 levels in serum and BALF
      were tested by enzyme linked immunosorbent assay (ELISA). The proportion of
      CD(4)(+)IL-17(+) T and CD(4)(+)Foxp3(+) Treg in peripheral blood and BALF were
      determined by flow cytometry. The mRNA expressions of IL-17 and Foxp3 were
      measured by real-time PCR. Comparisons of the data between different groups were
      performed using one-way ANOVA, and SNK and Games-Howell test were used for
      comparison between 2 groups. RESULTS: Levels of IL-17 were remarkable increased
      in the 12 wk smoke-exposure group and the 24 wk smoke-exposure group in serum
      [(52.6 +/- 1.8) ng/L, (75.4 +/- 6.0) ng/L] and BALF [(78.1 +/- 5.8) ng/L, (95.0
      +/- 6.8) ng/L] compared with the 12 wk control group [(40.0 +/- 3.2)ng/L, (54.5
      +/- 4.6) ng/L] and the 24 wk control group [(36.7 +/- 3.2) ng/L, (53.9 +/- 3.7)
      ng/L], all P < 0.05. IL-6 in serum was significantly increased in the 24 wk smoke
      exposure group [(31.4 +/- 2.1) ng/L] compared with the 24 wk control group [(11.5
      +/- 0.5) ng/L], and it was increased in the 12 wk and the 24 wk smoke-exposure
      group [(33.3 +/- 2.3) ng/L, (44.6 +/- 3.0) ng/L] compared with the 12 wk and the
      24 wk control group [(15.6 +/- 1.8) ng/L, (18.0 +/- 1.9) ng/L] in BALF. Ratio of
      Th17 was higher in the 12 wk and the 24 wk smoke-exposure groups in peripheral
      blood [(1.81 +/- 0.19)%, (3.74 +/- 0.55)%] and BALF [(7.84 +/- 0.28)%, (8.01 +/-
      0.39)%] compared with the12 wk [(0.97 +/- 0.08)%, (5.64 +/- 0.54)%] and the 24 wk
      control group [(1.08 +/- 0.10)%, (5.95 +/- 0.48)%]. Ratio of Treg in BALF was
      higher in the smoke-exposure groups [(8.81 +/- 0.49)%, (11.98 +/- 0.72)%]
      compared with the control groups [(4.34 +/- 0.28)%, (5.21 +/- 0.42)%]. The level
      of IL-17 mRNA was increased in the 12 wk and the 24 wk smoke-exposure group in
      peripheral blood (25.7 +/- 2.0, 33.9 +/- 1.5) and in BALF (22.2 +/- 1.8, 34.7 +/-
      4.2) compared with the 12 wk (11.3 +/- 2.6, 11.6 +/- 2.4) and the 24 wk (11.1 +/-
      2.0, 13.5 +/- 3.4) control groups. Foxp3 mRNA was increased in the smoke-exposure
      groups (24.4 +/- 2.7, 30.3 +/- 2.7) compared with the control groups (12.7 +/-
      2.7, 14.6 +/- 3.8). Th17 in smoke-exposure groups was positively correlated with
      counts of total cells and macrophages (r = 0.512, 0.543, all P < 0.05).
      CONCLUSIONS: An elevated expression of Th17 and Treg cells and an increase of
      inflammatory cytokines were evident in airway inflammation of cigarette smoke
      exposed rats, suggesting that Treg was involved in the immunological regulation
      and Th17 was associated with the persistent inflammation in cigarette smoke
      induced airway inflammation in rats.

PMID- 22455946
TI  - [The prevalence of influenza virus A in 2010 - 2011].

PMID- 22455947
TI  - [Advances in the diagnosis and treatment of cough variant asthma].

PMID- 22455948
TI  - Is E-cadherin immunoexpression a prognostic factor for head and neck squamous
      cell carcinoma (HNSCC)? A systematic review and meta-analysis.
AB  - We summarized existing evidence about whether the aberrant E-cadherin expression
      is a prognostic factor for patients with HNSCC. Identifying relevant articles,
      filtrating studies and extracting data were independently conducted by two
      reviewers. The quality of eligible studies was assessed according to systematic
      score criteria. Associations between aberrant E-cadherin expression and overall
      survival (OS) or disease-free survival (DFS) were summarized by hazard ratio (HR)
      estimates. Random or fixed effects models were used to investigate the effect of
      E-cadherin across the studies. According to the multivariate and univariate
      analyses, the meta-analysis of the included studies gave a statistically
      significant pooled HR for OS in HNSCC [the pooled HR=2.533; 95% confidence
      interval (CI)=1.971-3.254]. In addition, the subgroup analyses showed that the
      pooled HR of each subgroup also exhibited statistical significance according to
      the subpopulations (Asian and other subpopulations), treatments (surgery and
      other treatments), locations of primary tumors (oral cavity and other subsites),
      and data sources of HR (reported and estimated HR). Similar to the results of OS,
      the analysis of four included trials showed that the aberrant E-cadherin
      expression could predict low DFS. Meanwhile, a cumulative meta-analysis showed
      that the pooled HR became statistically significant. However, a meta-regression
      analysis showed that the OS was not statistically significant with the cutoff
      values of the included studies. Our study gives an important piece of evidence
      that aberrant E-cadherin expression was associated with a poor prognosis in
      patients with HNSCC.

PMID- 22455949
TI  - [Utility of monitoring intra-abdominal pressure in critically ill children].
AB  - OBJECTIVE: To assess the usefulness of intra-abdominal pressure (IAP)
      measurement, by the intra-vesical method, in order to identify those patients at
      risk of developing intra-abdominal hypertension, as well as to analyse the
      factors that affect the IAP, and to determine their influence on the prognosis in
      critically ill patients. PATIENTS AND METHODS: Prospective observational study in
      critically ill children in whom the IAP was monitored as soon as signs of intra
      abdominal hypertension appeared. The following variables were analysed: age, sex,
      reason for admission, underlying disease, previous surgeries, blood pressure,
      heart rate, central venous pressure, urine output, inotropic therapy, sedation,
      muscle relaxation, mechanical ventilation, renal replacement techniques,
      extracorporeal membrane oxygenation, and mortality. RESULTS: A total of 39
      patients were studied. At 24hours from initiating the monitoring of IAP, 74.4%
      showed IAP >= 12mmHg, 33.3%>15mmHg, and 15.4%>20mmHg. After 48hours, 59% had
      intra-abdominal hypertension. There was a correlation between the central venous
      pressure (CVP) and IAP at 24 and 48hours (r=0.500, P=.001 and r=0.360, P=.040,
      respectively). There was no correlation with the other parameters. Only 9
      patients required urgent decompression and none developed abdominal compartment
      syndrome. CONCLUSIONS: IAP monitoring can be useful to diagnose and to promptly
      treat intra-abdominal hypertension, and thus to prevent the abdominal compartment
      syndrome. Therefore, it should be measured in critically ill children with
      abdominal pathology.

PMID- 22455950
TI  - Urinary concentrations of organophosphorus insecticide metabolites in Japanese
      workers.
AB  - A recent development in analytical chemistry has enabled us to monitor systemic
      organophosphorus insecticide (OP) exposure at individual levels. At present,
      however, limited data are currently available on urinary OP metabolite levels
      worldwide. The purpose of this study was to assess urinary dialkylphosphate (DAP)
      concentrations in Japanese workers. Urine samples were collected in both summer
      and winter from 339 Japanese adults who worked as food distributors (FDs, n=164),
      apple farmers (AFs, n=147) and pest control operators (PCOs, n=28). DAPs were
      measured by gas chromatography-mass spectrometry after derivatization with
      pentafluorobenzylbromide. Dimethylphosphate (DMP), diethylphosphate (DEP),
      dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP) were detected in the
      urine of over 87% of the studied populations in both seasons. The geometric mean
      values of total DAPs (nmol g(-1) creatinine), DMP, DMTP, DEP and DETP (MUg g(-1)
      creatinine) in summer and winter were 106.7 and 98.3, 7.0 and 3.8, 3.4 and 4.5,
      0.8 and 1.5, and 0.3 and 0.2 for the FDs, 440.8 and 197.7, 33.1 and 10.8, 10.1
      and 5.8, 4.2 and 4.7 and 1.6 and 0.8 for the AFs, and 473.4 and 284.6, 28.9 and
      22.2, 17.6 and 4.6, 3.5 and 4.4, and 0.5 and 0.6 for the PCOs, respectively,
      thereby revealing significantly higher concentrations in AFs and PCOs groups than
      in the FDs in both seasons except for winter DMTP. These DAP concentrations were
      approximately the same or at lower levels compared with those reported in the
      previous literature. This is one of the first studies to demonstrate urinary DAP
      concentrations in Japanese adults.

PMID- 22455951
TI  - Tolerance of lead by the fruiting body of Oudemansiella radicata.
AB  - This study focused on the tolerance responses of the fruiting body of
      Oudemansiella radicata towards different concentrations of lead (250-1000 mg kg(
      1)) for 2-6 d. To know about the lead tolerance and detoxification strategy, the
      lead content, thiol content and the activities of antioxidant enzymes were
      investigated. The maximum level for the lead concentration in O. radicata was
      recorded in the 6 d sample in each treatment, and for thiols, it was recorded in
      the 500 mg kg(-1) Pb/2d sample, while for superoxide dismutases (SOD) and
      catalases (CAT) activities, it was reached at 1000 mg kg(-1) Pb after 2 d in the
      stipe and cap, respectively. Peroxidases (POD) activities showed a more complex
      trend and glutathione reductases (GR) reached the maximum at 500 mg kg(-1) Pb
      after 2 d in the stipe. Overall, the results showed that low concentration lead
      stimulated the fruiting body of O. radicata to produce the thiols and activate
      the antioxidant enzymes after 2 d/4 d, while high concentration Pb resulted in
      the decline/decrease of the thiols and the activities of antioxidant enzymes
      after 4 d/6 d. Benefiting from the metal accumulation, detoxification potential
      and the short lifetime, mushroom have the potential for bioaccumulation of heavy
      metal in polluted farmland.

PMID- 22455952
TI  - Stereotypic information about drinkers and students' observed alcohol intake: an
      experimental study on prototype-behavior relations in males and females in a
      naturalistic drinking context.
AB  - BACKGROUND: Cross-sectional and longitudinal research has shown that favorable
      drinker prototypes (i.e., perceptions about the typical drinker) are related to
      higher levels of alcohol consumption in adolescents and college students. So far,
      few studies have experimentally tested the causality of this relationship and it
      is not clear what type of manipulation affects drinker prototypes and drinking
      levels. METHODS: In an experimental 1-factor design with two levels, we tested
      the short-term effects of exposing students to either positive or negative
      stereotypic information about drinkers on their drinker prototypes and actual
      drinking behaviors. We exposed 192 male and female college students to positive
      drinker prototype information (drinkers in general were presented as being
      attractive, sociable and successful), or to negative information (unattractive,
      unsociable and unsuccessful). Subsequently, participants' levels of alcohol
      consumption were observed unobtrusively while they were interacting with peers in
      a naturalistic drinking context, namely a bar lab. RESULTS: Participants exposed
      to positive stereotypic information about drinkers reported more favorable
      drinker prototypes than participants exposed to negative stereotypic information.
      Multilevel analyses revealed that men's subsequent alcohol consumption in the bar
      lab was higher in the positive prototype condition than in the negative prototype
      condition. For women, no prototype effects on alcohol use were found.
      CONCLUSIONS: These findings underline that drinker prototypes affect actual
      alcohol use in men and suggest that changing perceptions of drinkers may be a
      useful tool in alcohol prevention programs.

PMID- 22455953
TI  - DNAJB6 governs a novel regulatory loop determining Wnt/beta-catenin signalling
      activity.
AB  - DKK1 (dickkopf 1 homologue) is a secreted inhibitor of the Wnt signalling pathway
      and a critical modulator of tumour promotion and the tumour microenvironment.
      However, mechanisms regulating DKK1 expression are understudied. DNAJB6 {DnaJ
      [HSP40 (heat-shock protein 40 kDa)] homologue, subfamily B, member 6} is an HSP40
      family member whose expression is compromised during progression of breast cancer
      and melanoma. Inhibition of the Wnt/beta-catenin signalling pathway by up
      regulation of DKK1 is one of the key mechanisms by which DNAJB6 suppresses tumour
      metastasis and EMT (epithelial-mesenchymal transition). Analysis of the DKK1
      promoter to define the cis-site responsible for its up-regulation by DNAJB6
      revealed the presence of two binding sites for a transcriptional repressor, MSX1
      (muscle segment homeobox 1). Our investigations showed that MSX1 binds the DKK1
      promoter and inhibits DKK1 transcription. Interestingly, silencing DNAJB6
      resulted in up-regulation of MSX1 concomitant with increased stabilization of
      beta-catenin. ChIP (chromatin immunoprecipitation) studies revealed that beta
      catenin binds the MSX1 promoter and stabilization of beta-catenin elevates MSX1
      transcription, indicating that beta-catenin works as a transcription co-activator
      for MSX1. Functionally, exogenous expression of MSX1 in DNAJB6-expressing cells
      promotes the mesenchymal phenotype by suppression of DKK1. Thus we have
      identified a novel regulatory mechanism of DNAJB6-mediated DKK1 transcriptional
      up-regulation that can influence EMT. DKK1 is a feedback regulator of beta
      catenin levels and thus our studies also define an additional negative control of
      this beta-catenin/DKK1 feedback loop by MSX1, which may potentially contribute to
      excessive stabilization of beta-catenin.

PMID- 22455954
TI  - Egr-1 contributes to IL-1-mediated down-regulation of peroxisome proliferator
      activated receptor gamma expression in human osteoarthritic chondrocytes.
AB  - INTRODUCTION: Peroxisome proliferator-activated receptor (PPAR)gamma has been
      shown to exhibit anti-inflammatory and anti-catabolic properties and to be
      protective in animal models of osteoarthritis (OA). We have previously shown that
      interleukin-1beta (IL-1) down-regulates PPARgamma expression in human OA
      chondrocytes. However, the mechanisms underlying this effect have not been well
      characterized. The PPARgamma promoter harbors an overlapping Egr-1/specificity
      protein 1 (Sp1) binding site. In this study, our objective was to define the
      roles of Egr-1 and Sp1 in IL-1-mediated down-regulation of PPARgamma expression.
      METHODS: Chondrocytes were stimulated with IL-1 and the expression levels of Egr
      1 and Sp1 mRNAs and proteins were evaluated using real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) and Western blotting, respectively. The role
      of de novo protein synthesis was evaluated using the protein synthesis inhibitor
      cycloheximide (CHX). The recruitment of Sp1 and Egr-1 to the PPARgamma promoter
      was evaluated using chromatin immunoprecipitation (ChIP) assays. The PPARgamma
      promoter activity was analyzed in transient transfection experiments. The roles
      of Egr-1 and Sp1 were further evaluated using small interfering RNA (siRNA)
      approaches. The level of Egr-1 in cartilage was determined using
      immunohistochemistry. RESULTS: Down-regulation of PPARgamma expression by IL-1
      requires de novo protein synthesis and was concomitant with the induction of the
      transcription factor Egr-1. Treatment with IL-1 induced Egr-1 recruitment and
      reduced Sp1 occupancy at the PPARgamma promoter. Overexpression of Egr-1
      potentiated, whereas overexpression of Sp1 alleviated, the suppressive effect of
      IL-1 on the PPARgamma promoter, suggesting that Egr-1 may mediate the suppressive
      effect of IL-1. Consistently, Egr-1 silencing prevented IL-1-mediated down
      regulation of PPARgamma expression. We also showed that the level of Egr-1
      expression was elevated in OA cartilage compared to normal cartilage.
      CONCLUSIONS: Our results indicate that induction and recruitment of Egr-1
      contributed to the suppressive effect of IL-1 on PPARgamma expression. They also
      suggest that modulation of Egr-1 levels in the joint may have therapeutic
      potential in OA.

PMID- 22455955
TI  - Multidisciplinarity and medical decision, impact for patients with cancer:
      sociological assessment of two tumour committees' organization.
AB  - PURPOSE: Medical practices in oncology are expected to be multidisciplinary, yet
      few articles studied how this may be concretely applied. In the present study, we
      evaluated the organization of two multidisciplinary committees, one for breast
      cancer and one for sarcoma, in a French Comprehensive Cancer Centre. METHODS:
      Both tumours were specifically chosen so as to emphasise substantial differences
      in relation with incidence, histological subtypes, management strategy, and
      scientific evidence. Between 2003 and 2004, 404 decision processes were observed,
      210 for sarcoma (26 meetings) and 194 for breast cancer (10 meetings). The number
      of physicians who took part in the discussions and their medical specialties were
      systematically noted as well as the number of contradictory discussions, medical
      specialties represented in these contradictory discussions and the topics of
      contradiction. The last measured data was whether the final committee's decision
      was in conformity with the referent preferences or not. All these measures were
      related to the referent's medical speciality and working place, to the stage of
      the disease and to the disease management stage. RESULTS: Committees'
      specificities concerned their organization, referent's medical specialties, the
      number of participants in discussions and their medical specialties. Discussions
      in the sarcoma committee tended to be more multidisciplinary, involving more
      specialties. Initial strategy proposal for one patient was modified during the
      discussions for 86 patients out of 210 (41%) and for 62 out of 194 (32%)
      respectively for sarcoma and breast cancer. However, there was no significant
      difference in the rate of contradictory discussions between breast cancer and
      sarcoma committees (32% versus 41% respectively; P = 0.08). The rates of
      contradictory discussions were similar for localized cancers, local relapse and
      metastasis disease (37%, 41% and 34% respectively; P = 0.86). CONCLUSIONS: The
      present study reports more than 30% of changes concerning strategy for patient
      with cancer due to multidisciplinary discussions. This indicates that, providing
      tumour committees are adapted to the pathologies' characteristics, they can
      promote a collective and multidisciplinary approach to oncology.

PMID- 22455956
TI  - Ion mobility-mass spectrometry (IM-MS) for top-down proteomics: increased dynamic
      range affords increased sequence coverage.
AB  - A general approach that combines mass spectrometry (MS), collision-induced
      dissociation (CID), ion mobility (IM), and MS for top-down proteomics is
      described, denoted as MS-CID-IM-MS. Using this approach, CID product ions are
      dispersed in two dimensions, specifically size-to-charge (IM) and mass-to-charge
      (MS), and the resulting 2D data display greatly facilitates peptide/protein mass
      mapping, amino acid sequence analysis, and determination of site-specific protein
      modifications. Also, this approach alleviates some of the inherent limitations of
      top-down proteomics, viz. the limitations in dynamic range for fragment ion
      abundances owing to the number of fragmentation channels available to large ionic
      systems as well as the resulting spectral congestion. For large peptides such as
      melittin (2845 Da), CID of the [M + 3H](3+), [M + 4H](4+), and [M + 5H](5+) ions
      yields amino acid sequence coverage of 42.3%, 38.5%, and 7.7%, respectively,
      whereas the hybrid MS-CID-IM-MS approach yields amino acid sequence coverages of
      84.6%, 65.4%, and 69.2%, respectively. For large biomolecules such as ubiquitin
      (8565 Da), the amino acid sequence coverage increases from 39% to 76%. The MS-CID
      IM-MS top-down approach allows for greater depth of information by allowing the
      assignment and study of internal fragment ions. Lastly, analysis of the methyl
      esterification of ubiquitin and single point mutation of human iron sulfur
      cluster U (HISCU, 14.3 kDa) demonstrates the ability of MS-CID-IM-MS to rapidly
      identify the presence and sites of modifications.

PMID- 22455957
TI  - Novel method for early investigation of bioactivity in different borate bio
      glasses.
AB  - Some ternary borate glasses were prepared and corrosion behavior of such ternary
      borate glasses after immersion in aqueous dilute phosphate solution was studied
      using different immersion times. Fourier transform infrared (FTIR) absorption
      spectral measurements were done before and after immersion in the mentioned
      solution for extended times up to 2 days to justify the appearance of the
      characteristic FTIR bands due to calcium phosphate (hydroxyapatite (HA)) which is
      considered as the potential indication of bioactivity. Experimental IR data
      confirm the beginning of the appearance of FTIR bands at about 580 and 620 cm(-1)
      after 3 days and the complete resolution with its characteristic split form after
      1 week and more. Deconvolution analysis technique (DAT) of the FTIR spectrum was
      employed to investigate the bioactivity of such ternary borate system after a
      short period of immersion. The corrosion behavior of such glasses is explained in
      relation to a suggested hydrolysis followed by direct dissolution mechanism. The
      ease of dissolution of all the borate glasses constituents explains the formation
      of calcium phosphate and conversion to crystalline hydroxyapatite within the
      borate glass matrix. X-ray diffraction may be used to retrace the structural
      changes and degree of crystallinity of the prepared glasses.

PMID- 22455958
TI  - [Novel methods for early diagnosis of lung cancer].

PMID- 22455959
TI  - [Epidemiology of lung cancer: review and perspective].

PMID- 22455960
TI  - [An overview of female non-small cell lung cancer].

PMID- 22455961
TI  - [Maintenance therapy in advanced non-small cell lung cancer: controversy and
      consensus].

PMID- 22455962
TI  - [Molecular targeted therapy in lung squamous carcinoma: there is always light at
      the end of the tunnel].

PMID- 22455963
TI  - [IASLC/ATS/ERS international multidisciplinary new classification of lung
      adenocarcinoma and its clinical significance].

PMID- 22455964
TI  - [Effect of pemetrexed plus platinum for chemotherapy-naive advanced non-small
      cell lung cancer].
AB  - OBJECTIVE: To evaluate the effect of pemetrexed plus platinum for chemotherapy
      naive advanced non-small cell lung cancer (NSCLC), and to explore thymidylate
      synthetase (TS) expression as the predictive and prognostic factor for this
      treatment. METHODS: This retrospective study enrolled 51 patients with
      chemotherapy-naive advanced NSCLC (non-squamous) treated at Department of
      Thoracic Medical Oncology in Beijing Cancer Hospital from Jan 2008 to Oct 2009.
      All patients received pemetrexed plus platinum as first-line treatment. TS
      expression was detected in 30 patients who had enough tissue samples by
      immunohistochemistry. RESULTS: The objective response rate (ORR) was 37.3%.
      Median progression-free survival (PFS) was 5.3 months (95%CI: 3.9 - 6.7), and
      median overall survival (OS) was 19.0 months (95%CI: 11.6 - 26.4). Univariate
      analysis showed that gender, pathology, smoking status and response were
      significantly correlated with OS. Cox-regression analysis showed that pathology
      was an independent prognostic factor. Rate of Grade 3/4 adverse events was low.
      In 30 patients with enough tissue samples were available, TS expression positive
      rate was 33.3% (10/30). Chi-square test showed that TS expression was not
      associated with ORR. Multivariate analysis showed that pathology, response and TS
      expression (P = 0.003, 0.005 and 0.001, respectively) were the prognostic
      factors. CONCLUSION: The therapeutic effect and tolerance of pemetrexed plus
      platinum regiment were definite as first-line treatment for chemotherapy-naive
      advanced NSCLC, and TS expression was an independent prognostic factor.

PMID- 22455965
TI  - [The level of soluble programmed death-1 in peripheral blood of patients with
      lung cancer and its clinical implications].
AB  - OBJECTIVE: To analyze the expression of soluble programmed death-1 ligand 1 (sPD
      L1) in the serum of patients with lung cancer and to explore its biological and
      clinical implications. METHODS: Fifty-five male and twenty-six female lung cancer
      patients ages 34 to 87 years (mean age 65 +/- 6) were selected from the
      Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow
      University from June 2009 to March 2011. All lung cancer patients were newly
      diagnosed, treatment-free and confirmed by histopathology or cytopathology. Eight
      eight healthy volunteers matching in sex and age from the Healthcare Center of
      the hospital were also enrolled as controls. The sPD-L1 protein expression in
      serum was determined by Western blot and self-developed ELISA kit. Fluorescence
      labeled monoclonal antibody and cytometry were used to examine changes in
      lymphocyte subsets in the peripheral blood of lung cancer patients and healthy
      controls. RESULTS: A higher level of sPD-L1 level in the lung cancer patients
      [1.6 (0.7 - 7.8) ug/L] was found compared to the control group [0.9 (0.4 - 3.7)
      ug/L] (P < 0.001). High expression of sPD-L1 in the lung cancer patients was
      closely correlated to lymph node metastasis and the extent of distant metastasis
      (chi(2) = 5.636, P < 0.05; chi(2) = 4.601, P < 0.05). The sPD-L1 level in lung
      cancer patients with objective response to treatment (complete response + partial
      response) was 2.7 (1.6 - 7.0) ug/L and 1.1 (0.8 - 1.7) ug/L before and after
      treatment, respectively (P < 0.01). The level of sPD-L1 with progression disease
      was 1.9 (1.3 - 8.5 ug/L) which was significantly increased compared to the
      baseline level 1.4 (0.8 - 2.2) ug/L (P < 0.01). Additionally, abnormal changes of
      T and B lymphocytes and their subsets were found, with a significant decrease of
      CD(8)(+) T lymphocytes (P < 0.05) and a rise in CD(4)/CD(8) ratio (P < 0.05).
      Further double-labeling study showed increased percentages of CD(4)(+)PD-1(+) T
      lymphocytes and CD(8)(+)PD-1(+) T lymphocytes (P < 0.05). CONCLUSIONS: The
      elevated expression of sPD-L1 in lung cancer patients was closely related to lung
      cancer staging, metastasis and clinical response. sPD-L1 may become a predictive
      marker and an important anti-tumor target in individualized treatment of lung
      cancer.

PMID- 22455966
TI  - [A study on the effects of indomethacin and oxaliplatin on lymphangiogenesis in a
      nude mice model of transplantation with A549 human lung cancer].
AB  - OBJECTIVE: To investigate the antitumor lymphangiogenesis activity and the
      synergistic effect of indomethacin and oxaliplatin in a transplantation tumor
      model of human lung cancer in nude mice. METHODS: Human lung cancer A549 cells
      were injected subcutaneously into BALB/c nude mice. The mice were randomly
      divided into 4 groups: the control group, the indomethacin group, the oxaliplatin
      group, and the indomethacin combined with oxaliplatin group. The tumor volume was
      measured in a 7 day interval, and the mice were sacrificed after 42 days. The
      tumor tissues were collected and prepared for detection by immunohistochemistry
      of expressions of VEGF-C, Survivin, beta-catenin and intratumoral microlymphatic
      density(MLD). Real-time fluorescence quantitative RT-PCR was performed for
      detecting the expression of VEGF-C and Survivin mRNA. SPSS version 16.0 was used
      for statistical analysis. Data were present as (x(-) +/- s), and means were
      compared with analysis of variance. The correlation of 2 variables was analyzed
      by liner correlation analysis. RESULTS: The tumor volumes in the indomethacin
      group, oxaliplatin group, and indomethacin plus oxaliplatin group [(1322 +/- 327)
      mm(3), (962 +/- 221) mm(3), (611 +/- 161) mm(3)] decreased significantly as
      compared with that of the control group [(1664 +/- 318) mm(3), F = 23.331, P <
      0.01]. Compared with the control group, the expression levels of VEGF-C,
      Survivin, beta-catenin and MLD protein in the indomethacin group, and
      indomethacin plus oxaliplatin group were significantly reduced (P < 0.05).
      Immunohistochemical studies showed an increase in the expression of VEGF-C in the
      oxaliplatin group (20 825 +/- 2067) as compared to the control group (16 075 +/-
      875, F = 97.24, P < 0.05), but no significant differences in beta-catenin and MLD
      (17 396 +/- 1693, 9666 +/- 978) as compared with the control group (9824 +/-
      1181, 17 588 +/- 1698)respectively, P > 0.05. VEGF-C and Survivin proteins were
      positively correlated with MLD respectively (t = 0.737, 0.662, respectively P <
      0.01), and beta-catenin protein was positively correlated with Survivin protein
      (r = 0.582, P < 0.01). VEGF-CmRNA was positively correlated with its protein (r =
      0.873, P < 0.01). CONCLUSION: The combined use of indomethacin and oxaliplatin
      promoted antitumor lymphangiogenesis activity, possible by inhibiting the VEGF
      C/VEGFR-3 and Wnt pathways.

PMID- 22455968
TI  - [A preliminary study on the relationship between HLA-Cw polymorphism and
      susceptibility to pulmonary tuberculosis].
AB  - OBJECTIVE: To analyze the relationship between HLA-Cw polymorphism and
      susceptibility to pulmonary tuberculosis (PTB), and therefore to explore the
      susceptible or resistant genes of PTB. METHODS: A hundred and twelve patients who
      were confirmed to have secondary PTB in Shandong Chest Hospital from May 2010 to
      May 2011 were selected as the PTB group, including 62 males and 50 females aged
      19 - 69 years (mean 41.7). According to the acid-fast staining results, PTB
      patients were divided into a smear-negative group (SN group, 77 cases) and a
      smear-positive group (SP group, 35 cases). A hundred and ten subjects who
      underwent physical examination in Shandong Chest Hospital at the same period were
      selected as the control group, including 59 males and 51 females aged 21 - 67
      years (mean 38.3). After genomic DNA was extracted, genotyping of HLA-Cw was
      conducted by sequence specific primer polymerase chain reaction (PCR-SSP) method.
      Then Hardy-Weinberg (H-W) equilibrium was tested, and gene frequencies(%) were
      estimated = 1-(1-phenotype frequencies)(1/2). Gene frequencies were compared
      between the PTB group and the control group, and between the SN group and SP
      group by chi(2) test. According to Bonferroni's principle, alpha was divided by
      the number of alleles (n = 8), and P < 0.006 25 was regarded as statistically
      significant. RESULTS: The frequency of HLA-Cw08 was significantly higher in PTB
      patients (43.6%, 75/112) compared with the controls (27.4%, 52/110), chi(2) =
      8.790, P < 0.006 25. Among PTB patients, HLA-Cw04 had a significantly higher
      frequency in the SP group (20.7%, 13/35) than in the SN group (4.7%, 7/77), while
      HLA-Cw08 had a significantly lower frequency in the SP group (22.5%, 14/35) than
      in the SN group (54.4%, 61/77), chi(2) = 12.909, 16.732, both P < 0.006 25.
      CONCLUSIONS: HLA-Cw polymorphism is related to susceptibility to PTB. HLA-Cw08
      may be one of the susceptible genes for PTB, and HLA-Cw04 and 08 may be related
      to MTB infectious status and clinical outcomes.

PMID- 22455967
TI  - [Antimicrobial susceptibility of community-acquired respiratory tract pathogens
      isolated from adults in China during 2009 and 2010].
AB  - OBJECTIVE: To investigate the drug-resistance rates of community-acquired
      respiratory tract pathogens isolated from adults in China during 2009 and 2010.
      METHODS: A total of 1793 strains (S. aureus 421, S. pneumoniae 420, K. pneumoniae
      404, H. influenzae 313, other Streptococcus. spp 149, and M. catarrhalis 86) of
      non-duplicated community-acquired respiratory tract pathogens were isolated from
      11 hospitals in 6 cities. The MIC values were determined by the broth
      microdilution method, and the production of beta-lactamase was tested using a
      nitrocefin-based test. RESULTS: All of the S.aureus isolates were methicillin
      sensitive (MSSA). Of the MSSA isolates, less than 1% (4/421) was resistant to
      beta-lactamase inhibitor combinations, about 13.1% (55/421) and 9% (38/421)
      resistant to levofloxacin and moxifloxacin, and 57% (240/421), 53.2% (224/421),
      and 88.7% (373/421) resistant to azithromycin, clarithromycin, and penicillin,
      respectively. No S. aureus isolates resistant to vancomycin were detected in this
      study. Based on different criteria, the percentages of penicillin-sensitive S.
      pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin
      resistant S. pneumoniae (PRSP) were 24.4% (102/420), 27.3% (115/420), 48.3%
      (203/420) (Oral) and 1.9% (8/420), 9% (38/420), 89.1% (374/420) (parenteral),
      respectively. The resistance rates of S. pneumonia to azithromycin,
      clarithromycin, cefaclor, cefuroxime, ceftriaxone and amoxicillin with clavulanic
      acid were 88.2% (370/420), 87.4% (367/420), 45.3% (190/420), 41.9% (176/420),
      10.2% (43/420), and 5.2% (22/420), respectively. About 2.6% (11/420) and 0.2%
      (1/420) of S. pneumonia isolates were resistant to levofloxacin and moxifloxacin.
      More than 70% (104/149) of beta-hemolytic streptococci isolates were resistant to
      azithromycin and clarithromycin, and about 10.1% (15/149) of isolates were
      resistant to levofloxacin. The resistance rates of K.pneumonia to most
      antibiotics were > 20% (81/404), and that of ceftazidime was lower than
      cefuroxime, cefaclor, and ceftriaxone. The mean prevalence value of ESBL
      producing K. pneumonia was 38.8% (157/404), with significantly regional
      variations. More than 90% of H. influenza and M. catarrhalis were susceptible to
      most antibiotics, with resistance rate of < 5% (16/313, H. influenza; 4/86, M.
      catarrhalis). The mean productions of beta-lactamase in H. influenza and M.
      catarrhalis were 13.1% (41/313) and 91.7% (79/86), respectively. CONCLUSIONS: The
      percentage of PRSP increased significantly, and the resistance rates of community
      acquired respiratory tract pathogens to common antibiotics such as macrolide and
      cephalosporins increased gradually. New fluoroquinolones such as moxifloxacin
      showed a high antimicrobial activity against most of the respiratory pathogens.

PMID- 22455969
TI  - [Anaplastic lymphoma kinase with the echinoderm microtubule-associated protein
      like 4, fusion gene and non-small cell lung cancer].

PMID- 22455970
TI  - [Venous thromboembolic diseases in 2011].

PMID- 22455971
TI  - [Progress in pharmacologic treatment of respiratory virus infection].

PMID- 22455972
TI  - Effects of progressive muscular relaxation training on anxiety, depression and
      quality of life of endometriosis patients under gonadotrophin-releasing hormone
      agonist therapy.
AB  - OBJECTIVES: To explore the effects of progressive muscle relaxation (PMR)
      training on anxiety, depression and quality of life (QOL) of endometriosis
      patients under gonadotrophin-releasing hormone (GnRH) agonist therapy. STUDY
      DESIGN: This was a controlled, randomized, open-label study. One hundred
      consecutive Han Chinese endometriosis patients, aged 18-48 years, were randomly
      assigned to a PMR group (n=50) and a control group (n=50). In a study of 12
      weeks' duration, both groups received one dose of depot leuprolide, 11.25mg IM.
      In addition to the GnRH agonist therapy, the PMR group received 12 weeks of PMR
      training. Anxiety level was measured using the state-trait anxiety inventory
      (STAI). Depression was assessed using subscale D of the hospital anxiety and
      depression scale (HADS-D). Health-related QOL was measured with SF-36 instrument.
      The patients were evaluated with STAI, HADS-D and SF-36 before and after the PMR
      intervention. RESULTS: The control group and the PMR group were comparable at
      baseline. After 12 weeks of intervention, both groups showed significant
      improvement in overall QOL (P<0.05). The PMR group, but not the control group,
      showed significant improvement in state anxiety, trait anxiety and depression
      after intervention (P<0.05). Moreover, the PMR group showed significant
      improvement in all QOL domains after intervention; by contrast, the control group
      showed significant improvement in all physical health domains and only two mental
      health domains after intervention. Between-group comparisons of the improvement
      in scores after intervention showed that the PMR group had significantly better
      improvement in the scores of anxiety, depression and overall/domain QOL than the
      control group (P<0.05). Repeated measures ANOVA revealed that both PMR
      intervention and time had significant individual as well as interactive effects
      on state anxiety, trait anxiety depression and overall QOL (P<0.05). CONCLUSIONS:
      This study suggests that PMR training is effective in improving anxiety,
      depression and QOL of endometriosis patients under GnRH agonist therapy. This is
      the first study to explore the effects of psychosomatic therapy on emotional
      status and QOL of endometriosis patients, and may serve as an important reference
      for future psychosomatic interventions on endometriosis.

PMID- 22455973
TI  - Microvesicles derived from endothelial progenitor cells enhance neoangiogenesis
      of human pancreatic islets.
AB  - The efficacy of islet transplantation is limited by poor graft vascularization.
      We herein demonstrated that microvesicles (MVs) released from endothelial
      progenitor cells (EPCs) enhanced human islet vascularization. After incorporation
      into islet endothelium and beta-cells, EPC-derived  MVs favored insulin
      secretion, survival, and revascularization of islets transplanted in SCID mice.
      MVs induced in vitro islet endothelial cell proliferation, migration, resistance
      to apoptosis, and organization in vessel-like structures. Moreover, MVs partially
      overcame the antiangiogenic  effect of rapamycin and inhibited endothelial
      leukocyte interaction via L-selectin and CD40. MVs were previously shown to
      contain defined patterns of mRNAs. Here we demonstrated that MVs carried the
      proangiogenic miR-126 and miR-296 microRNAs (miRNAs). MVs pretreated with RNase
      or derived  from Dicer knocked-down EPCs showed a reduced angiogenic effect. In
      addition, MVs overcame the antiangiogenic effect of the specific antagomiRs of
      miR-126 and miR-296, suggesting a relevant contribution of miRNAs delivered by
      MVs to islet endothelium. Microarray analysis of MV-stimulated islet  endothelium
      indicated the upregulation of mRNAs coding for factors involved in endothelial
      proliferation, differentiation, and angiogenesis. In addition, MVs induced the
      activation of the PI3K-Akt and eNOS signaling pathways in islet endothelium.
      These results suggest that MVs activate an  angiogenic program in islet
      endothelium that may sustain revascularization and beta-cell function.

PMID- 22455974
TI  - Radiocesium and radioiodine in soil particles agitated by agricultural practices:
      field observation after the Fukushima nuclear accident.
AB  - Three weeks after the accident at the Fukushima Daiichi Nuclear Power Plant, we
      determined the activity concentrations of (131)I, (134)Cs and (137)Cs in
      atmospheric dust fugitively resuspended from soil particles due to soil surface
      perturbation by agricultural practices. The atmospheric concentrations of (131)I,
      (134)Cs and (137)Cs increased because of the agitation of soil particles by a
      hammer-knife mower and a rotary tiller. Coarse soil particles were primarily
      agitated by the perturbation of the soil surface of Andosols. For dust particles
      smaller than 10 MUm, the resuspension factors of radiocesium during the operation
      of agricultural equipment were 16-times higher than those under background
      condition. Before tillage, most of the radionuclides accumulated within a few cm
      of the soil surface. Tillage diluted their concentration in the uppermost soil
      layer.

PMID- 22455975
TI  - Multimodal imaging and detection strategy with 124 I-labeled chimeric monoclonal
      antibody cG250 for accurate localization and confirmation of extent of disease
      during laparoscopic and open surgical resection of clear cell renal cell
      carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for approximately 85% to 90% of all primary
      kidney malignancies, with clear cell RCC (ccRCC) constituting approximately 70%
      to 85% of all RCCs. This study describes an innovative multimodal imaging and
      detection strategy that uses (124)I-labeled chimeric monoclonal antibody G250
      ((124)I-cG250) for accurate preoperative and intraoperative localization and
      confirmation of extent of disease for both laparoscopic and open surgical
      resection of ccRCC. Two cases presented herein highlight how this technology can
      potentially guide complete surgical resection and confirm complete removal of all
      diseased tissues. This innovative (124)I-cG250 (ie, (124)I-girentuximab)
      multimodal imaging and detection approach, which would be clinically very useful
      to urologic surgeons, urologic medical oncologists, nuclear medicine physicians,
      radiologists, and pathologists who are involved in the care of ccRCC patients,
      holds great potential for improving the diagnostic accuracy, operative planning
      and approach, verification of disease resection, and monitoring for evidence of
      disease recurrence in ccRCC patients.

PMID- 22455976
TI  - Critical factors affecting cell encapsulation in superporous hydrogels.
AB  - We recently showed that superporous hydrogel (SPH) scaffolds promote long-term
      stem cell viability and cell driven mineralization when cells were seeded within
      the pores of pre-fabricated SPH scaffolds. The possibility of cell encapsulation
      within the SPH matrix during its fabrication was further explored in this study.
      The impact of each chemical component used in SPH fabrication and each step of
      the fabrication process on cell viability was systematically examined. Ammonium
      persulfate, an initiator, and sodium bicarbonate, the gas-generating compound,
      were the two components having significant toxicity toward encapsulated cells at
      the concentrations necessary for SPH fabrication. Cell survival rates were 55.7%
      +/- 19.3% and 88.8% +/- 9.4% after 10 min exposure to ammonium persulfate and
      sodium bicarbonate solutions, respectively. In addition, solution pH change via
      the addition of sodium bicarbonate had significant toxicity toward encapsulated
      cells with cell survival of only 50.3% +/- 2.5%. Despite toxicity of chemical
      components and the SPH fabrication method, cells still exhibited significant
      overall survival rates within SPHs of 81.2% +/- 6.8% and 67.0% +/- 0.9%,
      respectively, 48 and 72 h after encapsulation. This method of cell encapsulation
      holds promise for use in vitro and in vivo as a scaffold material for both
      hydrogel matrix encapsulation and cell seeding within the pores.

PMID- 22455977
TI  - Monolithic LaBr3:Ce crystals on silicon photomultiplier arrays for time-of-flight
      positron emission tomography.
AB  - Positron emission tomography detectors based on monolithic scintillation crystals
      exhibit good spatial and energy resolution, intrinsically provide depth-of
      interaction information, have high gamma-photon capture efficiency, and may
      reduce the manufacturing costs compared to pixelated crystal arrays. Here, we
      present the characterization of a detector consisting of a 18.0 mm*16.2 mm*10.0
      mm monolithic LaBr3:5%Ce scintillator directly coupled to a 4*4 array of silicon
      photomultipliers. An energy resolution of 6.4% full-width-at-half-maximum (FWHM)
      was obtained. The point-spread-function (PSF) was determined for different
      regions of the detector. The full-width-at-half-maximum (FWHM) of the PSF was
      measured to be <1.5 mm at the center of the detector and <1.7 mm averaged over
      the entire crystal. Both values are not corrected for the ~0.6 mm FWHM test beam
      diameter. Furthermore, the influence of edge effects was investigated. We found
      that near the edges of the detector the spatial resolution degrades to 2.2 mm
      (FWHM), and a bias in the position estimates, up to 1.5 mm, was observed.
      Moreover, the coincidence resolving time for two identical detectors in
      coincidence was measured to be as small as ~198 ps FWHM.

PMID- 22455978
TI  - Genetic polymorphism of 17 STR loci in Chinese population from Hunan province in
      Central South China.

PMID- 22455979
TI  - Re: Maurizio A. Brausi. Challenging the EAU guidelines regarding early repeat
      transurethral resection. Eur Urol Suppl 2011;10:e5-7.

PMID- 22455980
TI  - Neuronal expression of F-box and leucine-rich-repeat protein 2 decreases over
      Braak stages in the brains of Alzheimer's disease patients.
AB  - BACKGROUND: The dysfunction of protein degradation through the ubiquitin
      proteasome system is now widely accepted as one of the causes of Alzheimer's
      disease (AD), the pathological hallmarks of which are abnormal protein
      accumulation such as senile plaques and neurofibrillary tangles in the brain.
      OBJECTIVE: To examine the expression of F-box and leucine-rich-repeat protein 2
      (FBL2), a member of the ubiquitin-protein ligase complex expected to be involved
      in the ubiquitin-proteasome system. METHODS AND RESULTS: We investigated the
      expression profile of FBL2 in the brains of AD patients by quantitative PCR and
      immunohistochemical analysis. In healthy subjects, the FBL2 mRNA level was very
      high in the brain when compared to other tissues. FBL2 immunoreactivities were
      detected in somata and dendrites in the neurons, but not detected in astrocytes
      or microglia. The FBL2 mRNA level decreased progressively in the brains of AD
      patients over Braak stages; this was more prominent in the temporal cortex (known
      to be a vulnerable region) than in the frontal cortex. Interestingly, the
      decrease was more severe in AD patients carrying the apolipoprotein E4 allele.
      The FBL2 IR also decreased over Braak stages, and was hardly detected at Braak
      stage 5 in both NeuN-positive and EAAC1-positive glutamatergic neurons.
      CONCLUSION: These results suggest that the involvement of the reduction of FBL2
      level is related to AD progression.

PMID- 22455981
TI  - Bioavailability, antioxidant and non toxic properties of a radioprotective
      formulation prepared from isolated compounds of Podophyllum hexandrum: a study in
      mouse model.
AB  - The current study was aimed to determine the stability, serum protein binding
      ability, biodistribution, antioxidant potential and tissue toxicity status of a
      novel radioprotective formulation (G-002M) from Podophyllum hexandrum. G-002M is
      the combination of a flavonoid, a lignan and its glucoside isolated from P.
      hexandrum rhizome that exhibit high radioprotective potential. Stability of G
      002M tagged with 99mTc was observed in vitro and with mice serum till 24 hr of
      incubation. The formulation was investigated for its antioxidant status and its
      bioavailability and toxicity in different organs of mice. Biodistribution study
      of 99mTc-G-002M revealed its uptake by all the vital organs of mice. Higher
      absorbed dose was observed in lungs, liver, jejunum and kidney. Maximum retention
      of G-002M in kidney revealed that G-002M was excreted predominantly through renal
      route. G-002M was also observed to have high free radical scavenging and total
      reducing properties. Histopathological observations showed no significant
      alterations in tissue morphology of lungs, liver, jejunum and kidney by G-002M
      administration. The data conclusively demonstrate that high stability, multi
      organ availability, longer retention and non-toxic behavior of G-002M might help
      in exhibiting strong protective potential against lethal radiation.

PMID- 22455982
TI  - ROS-mediated lipopolysaccharide-induced apoptosis in INS-1 cells by modulation of
      Bcl-2 and Bax.
AB  - Overproduction of reactive oxygen species (ROS) or exhaustion of antioxidants may
      cause oxidative stress which is a major factor of defective insulin secretion and
      increases apoptosis of pancreatic beta-cells in diabetes. So there comes a
      consideration of whether antioxidant strategies can be used to protect
      deterioration of the beta-cells. In this study, we explored the mechanism of
      oxidative stress mediated lipopolysaccharide (LPS) induced apoptosis in insulin
      secreting (INS-1) cells from a rat pancreatic beta-cell line. ROS was monitored
      by using intracellular ROS capture dihydroethidium (DHE) and dihydrorhodamine123
      (DHR123). Apoptosis rate was measured by flow cytometry (FCM). The pro-apoptotic
      gene Bax and anti-apoptotic gene Bcl-2 were analysed by Western blot and RT-PCR.
      The results demonstrate that LPS-stimulated INS-1 cells manifest intensified
      intracellular fluorescence in both dose- and time- dependent manners. Apoptosis
      rate of LPS stimulated INS-1 cells is significantly increased by FCM, with a
      significant increase in Bax/Bcl-2 ratio revealed by Western blot and RT-PCR.
      Furthermore, alpha-lipoic acid (alpha-LA) inhibits LPS-induced apoptosis, but can
      not restore the function of glucose stimulated insulin secretion (GSIS) in INS-1
      cells.

PMID- 22455983
TI  - Unfractionated heparin promotes LPS-induced endothelial barrier dysfunction: a
      preliminary study on the roles of angiopoietin/Tie2 axis.
AB  - INTRODUCTION: Heparins, including unfractionated heparin (UFH) and low-molecular
      weight heparins (LMWH), are anticoagulants approved as a treatment for severe
      sepsis, which can also prevent apoptosis and inflammation. The aim of this study
      was to investigate whether UFH prevents vascular leakage induced by
      lipopolysaccharide (LPS) and to define the role of angiopoietin (Ang)/Tie2
      signaling pathway since LPS is usually used to mimic the initiation of sepsis.
      METHODS: Human pulmonary microvascular endothelial cells (HPMECs) were pretreated
      with UFH (0.1 U/ml-10 U/ml), 15 min prior to stimulation with LPS (10 MUg/ml).
      Those samples not receiving LPS or UFH received an equal volume of Phosphate
      buffered saline (PBS). Cells were cultured under various experimental conditions
      for 2h, 6h or 12h for analysis. RESULTS: 1) Pretreatment with UFH significantly
      reduced HPMEC permeability compared with LPS-stimulated groups; 2) Pretreatment
      with UFH decreased the formation of stress fiber and intracellular gaps induced
      by LPS; 3) UFH significantly up-regulated gene expression of Tie2 and Ang-1 but
      down-regulated Ang-2 in HPMECs; 4) UFH prevented LPS-induced decrease in the
      level of ZO-1. CONCLUSION: This study demonstrates that UFH enhances endothelial
      barrier function and Ang/Tie2 axis probably represents one of the mechanisms by
      which UFH exerts its protective effect.

PMID- 22455984
TI  - Physiology to assist bedside prognostication in mechanically ventilated patients
      with chronic obstructive pulmonary disease.

PMID- 22455985
TI  - Pedestrian accident analysis with a silicone dummy block.
AB  - When a car is parked in an inclined plane in a parking lot, the car can roll down
      the slope and cause a pedestrian accident, even when the angle of inclination is
      small. A rolling car on a gentle slope seems to be easily halted by human power
      to prevent damage to the car or a possible accident. However, even if the car
      rolls down very slowly, it can cause severe injuries to a pedestrian, especially
      when the pedestrian cannot avoid the rolling car. In an accident case that
      happened in our province, a pedestrian was injured by a rolling car, which had
      been parked on a slope the night before. The accident occurred in the parking lot
      of an apartment complex. The parking lot seemed almost flat with the naked eye.
      We conducted a rolling test with the accident vehicle at the site. The car was
      made to roll down the slope by purely gravitational pull and was made to collide
      with the silicone block leaning against the retaining wall. Silicone has
      characteristics similar to those of a human body, especially with respect to
      stiffness. In the experiment, we measured the shock power quantitatively. The
      results showed that a rolling car could severely damage the chest of a
      pedestrian, even if it moved very slowly.

PMID- 22455986
TI  - A comparative study of phytochemical composition of genetically and non
      genetically modified soybean (Glycine max L.) and evaluation of antitumor
      activity.
AB  - Colon cancer is one of the major causes of cancer mortality worldwide. The
      analysed feeds, containing non-genetically modified (GM) soybean and Roundup
      Ready soybean, showed a different polyphenolic content and lipophilic
      composition. Non-GM soybean extract possessed twice the polyphenolic content of
      GM soybean and the highest number of sterols. Among them, gamma-sitosterol was
      found to be the major constituent. Methanolic extract of non-GM soybean extract
      was more potent than GM soybean extract against colon carcinoma cell line LoVo
      using MTT assay, while the second one showed a slightly higher anti-inflammatory
      activity. The findings add to epidemiological evidence for the therapeutic
      effects of soy foods in colorectal carcinoma.

PMID- 22455988
TI  - Antioxidant profile of selected Mediterranean red wines.
AB  - The polyphenolic composition and antioxidant properties of selected red wines
      from Morocco were evaluated. All of the wines tested showed very similar
      anthocyanin and flavonol patterns: individual compound contents resulted
      generally higher in comparison to conventional wines. Samples revealed a higher
      reducing capacity than radical scavenging property and a good correlation between
      antioxidant activity and polyphenolic content values. Each wine exhibited not
      only a moderate to high natural preserving capacity but also potentially
      beneficial influence on human health.

PMID- 22455987
TI  - Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair
      effect of BMP2 in a murine model of early osteoarthritis.
AB  - The goal of this study was to use bioengineered injectable microgels to enhance
      the action of bone morphogenetic protein 2 (BMP2) and stimulate cartilage matrix
      repair in a reversible animal model of osteoarthritis (OA). A module of perlecan
      (PlnD1) bearing heparan sulfate (HS) chains was covalently immobilized to
      hyaluronic acid (HA) microgels for the controlled release of BMP2 in vivo.
      Articular cartilage damage was induced in mice using a reversible model of
      experimental OA and was treated by intra-articular injection of PlnD1-HA
      particles with BMP2 bound to HS. Control injections consisted of BMP2-free PlnD1
      HA particles, HA particles, free BMP2 or saline. Knees dissected following these
      injections were analyzed using histological, immunostaining and gene expression
      approaches. Our results show that knees treated with PlnD1-HA/BMP2 had lesser OA
      like damage compared to control knees. In addition, the PlnD1-HA/BMP2-treated
      knees had higher mRNA levels encoding for type II collagen, proteoglycans and
      xylosyltransferase 1, a rate-limiting anabolic enzyme involved in the
      biosynthesis of glycosaminoglycan chains, relative to control knees (PlnD1-HA).
      This finding was paralleled by enhanced levels of aggrecan in the articular
      cartilage of PlnD1-HA/BMP2-treated knees. Additionally, decreases in the mRNA
      levels encoding for cartilage-degrading enzymes and type X collagen were seen
      relative to controls. In conclusion, PlnD1-HA microgels constitute a formulation
      improvement compared to HA for efficient in vivo delivery and stimulation of
      proteoglycan and cartilage matrix synthesis in mouse articular cartilage.
      Ultimately, PlnD1-HA/BMP2 may serve as an injectable therapeutic agent for
      slowing or inhibiting the onset of OA after knee injury.

PMID- 22455989
TI  - Comparative characterization of stem cells from human exfoliated deciduous teeth
      and dental pulp stem cells.
AB  - OBJECTIVE: This study focused on the characterization of stem cells from human
      exfoliated deciduous teeth (SHED) in comparison with dental pulp stem cells
      (DPSCs) to certify SHED as a key element in tissue engineering. METHODS: In the
      present study, SHED and DPSCs were assayed for their cell surface antigens and
      proliferation by measuring the cell cycles, growth rates, Ki67-positive
      efficiencies, and colony-forming units (CFUs). The evaluation of multi
      differentiation was performed using alizarin red and oil red O and real-time PCR
      in vitro. The mineralization capability of the cells was examined in vivo by
      implanting with ceramic bovine bone (CBB) into subcutaneous of immunocompromised
      mice for 8weeks. A three-dimensional pellet cultivation system is proposed for
      SHED and DPSCs to recreate the biological microenvironment that is similar to
      that of a regenerative milieu. RESULTS: SHED showed a higher proliferation rate
      and differentiation capability in comparison with DPSCs in vitro, and the results
      of the in vivo transplantation suggest that SHED have a higher capability of
      mineralization than the DPSCs. The mRNA expression levels of inflammatory
      cytokines, including matrix metalloproteinase-1 (MMP1), tissue inhibitors of
      metalloproteinase-1 (TIMP1), matrix metalloproteinase-2 (MMP2), tissue inhibitors
      of metalloproteinase-2 (TIMP2) and interleukin-6 (IL-6) were higher in SHED than
      that in DPSCs. In addition, the expression levels of Col I and proliferating cell
      nuclear antigen (PCNA) in SHED sheets were significantly higher than those in
      DPSCs sheets. CONCLUSIONS: This study systematically demonstrated the differences
      in the growth and differentiation characteristics between SHED and DPSCs.
      Consequently, SHED may represent a suitable, accessible and potential alternative
      source for regenerative medicine and therapeutic applications.

PMID- 22455990
TI  - A breathing thorax phantom with independently programmable 6D tumour motion for
      dosimetric measurements in radiation therapy.
AB  - Irradiation of moving targets using a scanned ion beam can cause clinically
      intolerable under- and overdosages within the target volume due to the interplay
      effect. Several motion mitigation techniques such as gating, beam tracking and
      rescanning are currently investigated to overcome this restriction. To enable
      detailed experimental studies of potential mitigation techniques a complex thorax
      phantom was developed. The phantom consists of an artificial thorax with ribs to
      introduce density changes. The contraction of the thorax can be controlled by a
      stepping motor. A robotic driven detector head positioned inside the thorax
      mimics e.g. a lung tumour. The detector head comprises 20 ionization chambers and
      5 radiographic films for target dose measurements. The phantom's breathing as
      well as the 6D tumour motion (3D translation, 3D rotation) can be programmed
      independently and adjusted online. This flexibility allows studying the
      dosimetric effects of correlation mismatches between internal and external
      motions, irregular breathing, or baseline drifts to name a few. Commercial motion
      detection systems, e.g. VisionRT or Anzai belt, can be mounted as they would be
      mounted in a patient case. They are used to control the 4D treatment delivery and
      to generate data for 4D dose calculation. To evaluate the phantom's properties,
      measurements addressing reproducibility, stability, temporal behaviour and
      performance of dedicated breathing manoeuvres were performed. In addition,
      initial dosimetric tests for treatment with a scanned carbon beam are reported.

PMID- 22455991
TI  - Silicon modifies root anatomy, and uptake and subcellular distribution of cadmium
      in young maize plants.
AB  - BACKGROUND AND AIMS: Silicon (Si) has been shown to ameliorate the negative
      influence of cadmium (Cd) on plant growth and development. However, the mechanism
      of this phenomenon is not fully understood. Here we describe the effect of Si on
      growth, and uptake and subcellular distribution of Cd in maize plants in relation
      to the development of root tissues. METHODS: Young maize plants (Zea mays) were
      cultivated for 10 d hydroponically with 5 or 50 um Cd and/or 5 mm Si. Growth
      parameters and the concentrations of Cd and Si were determined in root and shoot
      by atomic absorption spectrometry or inductively coupled plasma mass
      spectroscopy. The development of apoplasmic barriers (Casparian bands and suberin
      lamellae) and vascular tissues in roots were analysed, and the influence of Si on
      apoplasmic and symplasmic distribution of (109)Cd applied at 34 nm was
      investigated between root and shoot. KEY RESULTS: Si stimulated the growth of
      young maize plants exposed to Cd and influenced the development of Casparian
      bands and suberin lamellae as well as vascular tissues in root. Si did not affect
      the distribution of apoplasmic and symplasmic Cd in maize roots, but considerably
      decreased symplasmic and increased apoplasmic concentration of Cd in maize
      shoots. CONCLUSIONS: Differences in Cd uptake of roots and shoots are probably
      related to the development of apoplasmic barriers and maturation of vascular
      tissues in roots. Alleviation of Cd toxicity by Si might be attributed to
      enhanced binding of Cd to the apoplasmic fraction in maize shoots.

PMID- 22455992
TI  - Functional aspects of floral nectar secretion of Ananas ananassoides, an
      ornithophilous bromeliad from the Brazilian savanna.
AB  - BACKGROUND AND AIMS: Several members of Bromeliaceae show adaptations for
      hummingbird pollination in the Neotropics; however, the relationships between
      floral structure, nectar production, pollination and pollinators are poorly
      understood. The main goal of this study was to analyse the functional aspects of
      nectar secretion related to interaction with pollinators by evaluating floral
      biology, cellular and sub-cellular anatomy of the septal nectary and nectar
      composition of Ananas ananassoides, including an experimental approach to nectar
      dynamics. METHODS: Observations on floral anthesis and visitors were conducted in
      a population of A. ananassoides in the Brazilian savanna. Nectary samples were
      processed using standard methods for light and transmission electron microscopy.
      The main metabolites in nectary tissue were detected via histochemistry. Sugar
      composition was analysed by high-performance liquid chromatography (HPLC). The
      accumulated nectar was determined from bagged flowers ('unvisited'), and floral
      response to repeated nectar removal was evaluated in an experimental design
      simulating multiple visits by pollinators to the same flowers ('visited') over
      the course of anthesis. KEY RESULTS: The hummingbirds Hylocharis chrysura and
      Thalurania glaucopis were the most frequent pollinators. The interlocular septal
      nectary, composed of three lenticular canals, extends from the ovary base to the
      style base. It consists of a secretory epithelium and nectary parenchyma rich in
      starch grains, which are hydrolysed during nectar secretion. The median volume of
      nectar in recently opened 'unvisited' flowers was 27.0 uL, with a mean (sucrose
      dominated) sugar concentration of 30.5 %. Anthesis lasts approx. 11 h, and nectar
      secretion begins before sunrise. In 'visited' flowers (experimentally emptied
      every hour) the nectar total production per flower was significantly higher than
      in the 'unvisited' flowers (control) in terms of volume (t = 4.94, P = 0.0001)
      and mass of sugar (t = 2.95, P = 0.007), and the concentration was significantly
      lower (t = 8.04, P = 0.0001). CONCLUSIONS: The data suggest that the total
      production of floral nectar in A. ananassoides is linked to the pollinators'
      activity and that the rapid renewal of nectar is related to the nectary
      morphological features.

PMID- 22455993
TI  - Physical and rehabilitation medicine (PRM) care pathways: "patients after total
      knee arthroplasty".
AB  - This document is part of a series of documents designed by the French Physical
      and Rehabilitation Medicine Society (SOFMER) and the French Federation of PRM
      (FEDMER). These documents describe the needs for or a specific type of patients;
      PRM care objectives, human and material resources to be implemented, chronology
      as well as expected outcomes. "Care pathways in PRM" is a short document designed
      to enable the reader (physicians, decision-maker, administrator, lawyer or
      finance manager) to quickly apprehend the needs of these patients and the
      available therapeutic care structures for proper organization and pricing of
      these activities. Patients after total knee arthroplasty are classified into
      three care sequences and two clinical categories, each one being treated with the
      same six parameters according to the International Classification of Functioning,
      Disability and Health (WHO), while taking into account personal and environmental
      factors that could influence the needs of these patients.

PMID- 22455994
TI  - Trends in sustainable landfilling in Malaysia, a developing country.
AB  - In Malaysia, landfills are being filled up rapidly due to the current daily
      generation of approximately 30,000 tonnes of municipal solid waste. This
      situation creates the crucial need for improved landfilling practices, as
      sustainable landfilling technology is yet to be achieved here. The objective of
      this paper is to identify and evaluate the development and trends in landfilling
      practices in Malaysia. In 1970, the disposal sites in Malaysia were small and
      prevailing waste disposal practices was mere open-dumping. This network of
      relatively small dumps, typically located close to population centres, was
      considered acceptable for a relatively low population of 10 million in Malaysia.
      In the 1980s, a national programme was developed to manage municipal and
      industrial wastes more systematically and to reduce adverse environmental
      impacts. The early 1990s saw the privatization of waste management in many parts
      of Malaysia, and the establishment of the first sanitary landfills for MSW and an
      engineered landfill (called 'secure landfill' in Malaysia) for hazardous waste. A
      public uproar in 2007 due to contamination of a drinking water source from
      improper landfilling practices led to some significant changes in the
      government's policy regarding the country's waste management strategy. Parliament
      passed the Solid Waste and Public Cleansing Management (SWPCM) Act 2007 in August
      2007. Even though the Act is yet to be implemented, the government has taken big
      steps to improve waste management system further. The future of the waste
      management in Malaysia seems somewhat brighter with a clear waste management
      policy in place. There is now a foundation upon which to build a sound and
      sustainble waste management and disposal system in Malaysia.

PMID- 22455995
TI  - Novel Ocimumoside A and B as anti-stress agents: modulation of brain monoamines
      and antioxidant systems in chronic unpredictable stress model in rats.
AB  - Therapies targeting central stress mechanisms are fundamental for the development
      of successful treatment strategies. Ocimum sanctum (OS) is an Indian medicinal
      plant traditionally used for the treatment of various stress-related conditions.
      Previously, we have isolated and characterized three OS compounds; Ocimarin,
      Ocimumoside A and Ocimumoside B. However, their role in modulating chronic stress
      induced central changes is unexplored. Thus, in the present study the efficacy of
      these OS compounds have been evaluated on the chronic unpredictable stress (CUS)
      induced alterations in the monoaminergic and antioxidant systems in the frontal
      cortex, striatum and hippocampus, along with the changes in the plasma
      corticosterone levels. CUS (two different types of stressors daily for seven
      days) resulted in a significant elevation of plasma corticosterone level, which
      was reversed to control levels by pretreatment with Ocimumoside A and B (40 mg/kg
      p.o.), while Ocimarin showed no effect. The levels of NA, DA and 5-HT were
      significantly decreased in all the three brain regions by CUS, with a selective
      increase of DA metabolites. A significant decrease in the glutathione (GSH)
      content, the activities of superoxide dismutase and catalase with a significant
      increase in the glutathione peroxidase activity and lipid peroxidation was
      observed in all the three regions of the brain by CUS. The OS compounds alone did
      not cause any significant change in the baseline values of these parameters.
      However, Ocimumoside A and B (40 mg/kg body p.o.) attenuated these CUS-induced
      alterations with an efficacy similar to that of standard anti-stress (Panax
      quinquefolium; 100 mg/kg p.o.) and antioxidant (Melatonin; 20 mg/kg i.p.) drugs.
      While, Ocimarin failed to modulate these CUS-induced alterations. Therefore, this
      is the first report which identified the anti-stress activity of novel
      Ocimumoside A and B at the level of central monoamines and antioxidant
      properties, implicating their therapeutic importance in the prevention of stress
      related disorders.

PMID- 22455996
TI  - The multiple facets of dermcidin in cell survival and host defense.
AB  - Eccrine sweat glands, which are distributed over the whole bodies of primates and
      humans, have long been regarded mainly to have a function in thermoregulation.
      However, the discovery of dermcidin-derived antimicrobial peptides in eccrine
      sweat demonstrated that sweat actively participates in the constitutive innate
      immune defense of human skin against infection. In the meantime, a number of
      studies proved the importance of dermcidin in skin host defense. Several reports
      also state that peptides processed from the dermcidin precursor protein exhibit a
      range of other biological functions in neuronal and cancer cells. This review
      summarizes the evidence gathered until now concerning the expression of dermcidin
      and the functional relevance of dermcidin-derived peptides.

PMID- 22455997
TI  - Pulmonary hypertension in a child with mitochondrial A3243G point mutation.
AB  - Mitochondrial diseases are a group of disorders caused by pathologic dysfunction
      of the mitochondrial respiratory chain that present with a wide range of clinical
      expression. Cardiorespiratory complications have previously been described in
      association with mitochondrial disease; however, pulmonary hypertension has
      rarely been reported. Pulmonary hypertension is characterized by elevated
      pulmonary arterial pressure and secondary right ventricular failure. It is a life
      threatening condition with a poor prognosis if untreated. We report a case of 3
      year-4-month-old boy who had mitochondrial A3243G point mutation with pulmonary
      hypertension. The unusual features of our case strengthen the concepts of
      pulmonary hypertension should be considered as another potential manifestation of
      mitochondrial disease.

PMID- 22455998
TI  - Optimization of methods for quantification of rCBF using high-resolution [15O]H2O
      PET images.
AB  - This study aimed to derive accurate estimates of regional cerebral blood flow
      (rCBF) from noisy dynamic [15O]H2O PET images acquired on the high-resolution
      research tomograph, while retaining as much as possible the high spatial
      resolution of this brain scanner (2-3 mm) in parametric maps of rCBF. The PET
      autoradiographic method and generalized linear least-squares (GLLS), with fixed
      or extended to include spatially variable estimates of the dispersion of the
      measured input function, were compared to nonlinear least-squares (NLLS) for rCBF
      estimation. Six healthy volunteers underwent two [15O]H2O PET scans with
      continuous arterial blood sampling. rCBF estimates were obtained from three image
      reconstruction methods (one analytic and two iterative, of which one includes a
      resolution model) to which a range of post-reconstruction filters (3D Gaussian:
      2, 4 and 6 mm FWHM) were applied. The optimal injected activity was estimated to
      be around 11 MBq kg-1 (800 MBq) by extrapolation of patient-specific noise
      equivalent count rates. Whole-brain rCBF values were found to be relatively
      insensitive to the method of reconstruction and rCBF quantification. The grey and
      white matter rCBF for analytic reconstruction and NLLS were 0.44 +/- 0.03 and
      0.15 +/- 0.03 mL min-1 cm-3, respectively, in agreement with literature values.
      Similar values were obtained from the other methods. For generation of parametric
      images using GLLS or the autoradiographic method, a filter of >= 4 mm was
      required in order to suppress noise in the PET images which otherwise produced
      large biases in the rCBF estimates.

PMID- 22456000
TI  - Isolation of a p-hydroxyphenyl anhydride from the leaves of Diphysa
      carthagenensisw.
AB  - Diphysidione (1), a new p-hydroxyphenyl anhydride, and vitexin (2) were isolated
      from the leaves of Diphysa carthagenensis. The structure of the new metabolite
      was characterised as 4-(4-hydroxy-phenyl)-3H-pyran-2,6-dione using 1D and 2D NMR
      spectroscopy.

PMID- 22455999
TI  - Improved cartilage repair via in vitro pre-maturation of MSC-seeded hyaluronic
      acid hydrogels.
AB  - Functional repair of focal cartilage defects requires filling the space with
      neotissue that has compressive properties comparable to native tissue and
      integration with adjacent host cartilage. While poor integration is a common
      complication with current clinical treatments, reports of tissue engineering
      advances in the development of functional compressive properties rarely include
      analyses of their potential for integration. Our objective was thus to assess
      both the maturation and integration of mesenchymal stem cell (MSC)-laden
      hyaluronic acid (HA) hydrogels in an in vitro cartilage defect model.
      Furthermore, we considered the effects of an initial period of pre-maturation as
      well as various material formulations to maximize both construct compressive
      properties and integration strength. MSCs were encapsulated in 1%, 3% and 5%
      methacrylated HA (MeHA) or 2% agarose (Ag) and gelled directly (in situ) within
      an in vitro cartilage defect or were formed and then pre-cultured for 4 weeks
      before implantation. Results showed that the integration strength of pre-cultured
      repair constructs was equal to (1% MeHA) or greater than (2% Ag) the integration
      of in situ repaired cartilage. Moreover, MSC chondrogenesis and maturation was
      restricted by the in situ repair environment with constructs maturing to a much
      lesser extent than pre-matured constructs. These results indicate that construct
      pre-maturation may be an essential element of functional cartilage repair.

PMID- 22456001
TI  - Potential hepatotoxicity of geniposide, the major iridoid glycoside in dried ripe
      fruits of Gardenia jasminoides (Zhi-zi).
AB  - The safety of geniposide, mainly focusing on its hepatotoxicity in rats, was
      determined by liver enzymes in serum and histopathology ultrastructural
      preparation. The lethal dose, 50% (LD50) of per oral geniposide was 1431.1 mg kg(
      1). The acute toxicity study indicated geniposide at dose of 574 mg kg(-1) or
      more could cause hepatic toxicity in rats and the hepatotoxicity often appeared
      at 24-48 h after the oral administration. The hepatotoxicity was associated with
      oxidative stress with decrease of total superoxide dismutase activity and
      increase of malondialdehyde concentration in rats' livers. Subchronic toxicity
      study showed geniposide did not cause hepatotoxicity at the doses of 24.3 and
      72.9 mg kg(-1) orally for 90 days in rats. Thus, acute hepatotoxicity of
      geniposide at high doses was likely to be linked to oxidative stress, while
      geniposide at normal dose of 24.3 mg kg(-1) or less did not cause hepatotoxicity
      even in the repeated dosing study.

PMID- 22456002
TI  - Selection, thirty day outcome and costs for short stay endovascular aortic
      aneurysm repair (SEVAR).
AB  - BACKGROUND: Endovascular aortic aneurysm repair (EVAR) offers the potential for a
      reduced hospital stay. The aim of this study was to identify patients suitable
      for short stay EVAR (SEVAR) with a single night in hospital and document their
      outcome. METHOD: Patients for EVAR were assessed prospectively for SEVAR over a
      21-month period using UK Day Surgery Guidelines. Joint anaesthetic and surgical
      approval were necessary for these patients to be included in this vascular
      pathway. Patients were admitted on the day of surgery with a designated care
      protocol for discharge the day after. RESULTS: 101 patients were assessed for
      SEVAR. 33 (33%) patients met the criteria for SEVAR and 27 of these (81%) were
      successfully discharged one day post-operatively. Total SEVAR median LOS was one
      day (IQR = 0) versus four days (IQR = 2) for the standard EVAR group (P < 0.0001)
      reducing costs from L13,360 (CI = +/-1074) to L9844 (CI = +/-628). Increased
      utilisation of SEVAR during the study period led to reduced overall average EVAR
      costs, L12,102(CI = +/-795) to L10,330(CI = +/-757). CONCLUSION: SEVAR protocol
      reduces hospital stay for selected patients. The outcomes from a larger cohort of
      such patients require further study. This would identify whether SEVAR could be
      expanded to more patients.

PMID- 22456003
TI  - High-sensitive cardiac troponin T outperforms novel diagnostic biomarkers in
      patients with acute chest pain.
AB  - BACKGROUND: Measurement of high-sensitive cardiac troponin (hs-cTn) has
      facilitated the early diagnostic assessment of chest pain patients. However, the
      information obtained from hs-cTnT levels might be improved when combined with
      results of other biomarkers of myocardial injury. METHODS: We measured admission
      levels of hs-cTnT (Roche Diagnostics), heart-type fatty-acid binding protein (H
      FABP; Randox Laboratories) and copeptin using a novel ultra-sensitive (us) assay
      (Thermo Fisher Scientific) in 360 chest pain patients with a non-diagnostic ECG.
      Non-STEMI was defined according to the Universal Definition using cardiac
      troponin I (Stratus CS; Siemens Healthcare Diagnostics) as biochemical gold
      standard. RESULTS: Non-STEMI was diagnosed in 128 (36%) patients. Hs-cTnT had a
      greater diagnostic accuracy regarding non-STEMI (C-statistics 0.84) compared to H
      FABP (C-statistics 0.80; p=0.04) and us-copeptin C-statistics(0.62; p<0.001).
      Compared to hs-cTnT alone, no increase in the C-statistics was noted for the
      combination of hs-cTnT with H-FABP (0.85; p=0.43) or with us-copeptin (0.84;
      p=0.88). Due to suboptimal sensitivities and/or specificities, neither H-FABP nor
      us-copeptin dichotomized at commonly applied diagnostic thresholds added
      information to hs-cTnT that would have facilitated early diagnostic assessment.
      CONCLUSIONS: Hs-cTnT provides an excellent early diagnostic accuracy regarding
      non-STEMI already on admission. Neither H-FABP nor us-copeptin perform better or
      provide diagnostic increment to hs-cTnT levels.

PMID- 22456004
TI  - Age impacts extracellular matrix metabolism in chondrocytes encapsulated in
      degradable hydrogels.
AB  - Encapsulation of autologous adult cartilage cells (chondrocytes) in
      hydrolytically degradable hydrogels may provide a clinically viable tissue
      engineering therapy for replacement of damaged or osteoarthritic cartilage. When
      designing a tissue engineering scaffold, it is crucial to evaluate adult
      chondrocytes due to their limited growth potential. The objective for this study
      was to compare extracellular matrix anabolic and catabolic metabolisms by
      juvenile and adult chondrocytes in hydrolytically degradable hydrogels. Cells
      were photo-encapsulated in bimodal degradable hydrogels composed of slow
      degrading poly(ethylene glycol) (PEG) and the fast-degrading copolymer
      oligo(lactic acid)-b-PEG-b-oligo(lactic acid) crosslinks, and cultured through
      four weeks. Cell density was significantly higher in constructs containing adult
      cells, contributing to higher glycosaminoglycan content per wet weight. However,
      juvenile cells exhibited higher collagen content per cell. Immunohistochemical
      visualization revealed cartilage-specific aggrecan and collagen II deposition by
      both adult and juvenile cells. Immunohistochemically stained catabolically
      degraded collagen fragments and western blot-detected degraded aggrecan
      fragments, especially those associated with an osteoarthritic state, were more
      abundant in constructs with adult cells. Overall, bimodal degradable hydrogel
      environments were supportive of viable adult cells. However, major challenges
      with adult cells include their reduced collagen productivity and high catabolic
      activity, which may impact the quality of the engineered tissues.

PMID- 22456005
TI  - Response to Dr Kuhnisch.

PMID- 22456006
TI  - Influence of veneer application on fracture behavior of lithium-disilicate-based
      ceramic crowns.
AB  - OBJECTIVES: To assess the influence of veneer application on fracture behavior,
      namely failure load and failure mode, of standardized lithium-disilicate-based
      crowns. METHODS: Forty molar crowns (IPS e.max Press, IvoclarVivadent) were
      fabricated in full anatomic (without veneer, 1.5-2.0mm at occlusal surface) and
      bi-layer (the occlusal surface is 0.7 mm of veneer and 0.8-1.3mm core) contour
      representing two groups. Crown specimens were seated and adhered on composite
      resin dies. All specimens were loaded with a 6mm diameter steatite sphere over
      the central fissure to failure. Failure modes and fractographic patterns were
      analyzed by optical stereo and scanning electron microscopy (SEM). Fracture loads
      of the two groups were compared by the t-test, while the failure modes were
      analyzed by Pearson Chi-square test. RESULTS: There was a statistically
      significant difference in mean fracture load values (N+/-S.D.) between full
      anatomic [(2665.4+/-759.2)N] and veneered crowns [(1431.1+/-404.3)N] (p<0.001)
      and also in failure modes (chi(2)=6.465, p=0.011). Full anatomic crowns mainly
      showed bulk fracture, whereas veneered specimens predominately showed cohesive
      veneer and ceramic interface failure (75%); solely cohesive veneer failure (20%);
      and bulk fracture (5%). SIGNIFICANCE: Within the limitations of this study,
      veneer application resulted in significant lower fracture load values compared to
      full anatomic crowns. Fracture initiated from occlusal fissures near the load
      application site. A combination of cohesive veneer and ceramic interface failure
      represents the main failure mode of lithium-disilicate-based bi-layered crowns,
      whereas full anatomic crowns failed mainly from ceramic bulk fracture at the
      occlusal fissures.

PMID- 22456007
TI  - A comparative evaluation of polymerization stress data obtained with four
      different mechanical testing systems.
AB  - OBJECTIVES: The null hypothesis was that mechanical testing systems used to
      determine polymerization stress (sigma(pol)) would rank a series of composites
      similarly. METHODS: Two series of composites were tested in the following
      systems: universal testing machine (UTM) using glass rods as bonding substrate,
      UTM/acrylic rods, "low compliance device", and single cantilever device
      ("Bioman"). One series had five experimental composites containing BisGMA:TEGDMA
      in equimolar concentrations and 60, 65, 70, 75 or 80 wt% of filler. The other
      series had five commercial composites: Filtek Z250 (3M ESPE), Filtek A110 (3M
      ESPE), Tetric Ceram (Ivoclar), Heliomolar (Ivoclar) and Point 4 (Kerr). Specimen
      geometry, dimensions and curing conditions were similar in all systems.
      sigma(pol) was monitored for 10 min. Volumetric shrinkage (VS) was measured in a
      mercury dilatometer and elastic modulus (E) was determined by three-point
      bending. Shrinkage rate was used as a measure of reaction kinetics. ANOVA/Tukey
      test was performed for each variable, separately for each series. RESULTS: For
      the experimental composites, sigma(pol) decreased with filler content in all
      systems, following the variation in VS. For commercial materials, sigma(pol) did
      not vary in the UTM/acrylic system and showed very few similarities in rankings
      in the others tests system. Also, no clear relationships were observed between
      sigma(pol) and VS or E. SIGNIFICANCE: The testing systems showed a good agreement
      for the experimental composites, but very few similarities for the commercial
      composites. Therefore, comparison of polymerization stress results from different
      devices must be done carefully.

PMID- 22456008
TI  - Person: centre both of clinical ethics  and of public health ethics. Commentary.
AB  - The "public health" perspective is different from the "patient-centred" clinical
      perspective for various reasons. Tensions between collective and individual
      interests are unavoidable in public health. Intersections between public health
      ethics and clinical bioethics can be traced to a set of duties which derive from
      respect of the person. Human rights and solidarity are "person-centred"
      cornerstones of both clinical and public health ethics.

PMID- 22456009
TI  - A new technology in biomedical engineering analysis: the 3-Dimensional
      microtomography. Preface.

PMID- 22456010
TI  - Role of X-ray microtomography in tissue engineering.
AB  - The structure and architecture of scaffolds are crucial factors in scaffolds
      based tissue engineering since they affect the functionality of the tissue
      engineering construct and the eventual application in health care. Therefore,
      effective scaffold assessment techniques are required right at the initial stages
      of research and development so as to select or design scaffolds with suitable
      properties. Furthermore, since the biological performances of a scaffold is
      evaluated with respect to its capacity of favouring cell adhesion, proliferation
      as well as production of extracellular matrix, it is important to have an
      analytical technique able to monitor the various stages of cell culture both in
      vitro and especially in vivo. Finally, the development of a vascular network
      inside the cell scaffold construct is a fundamental requisite for achieving a
      full integration of the developing tissue with the host tissue. Also in this
      respect it is mandatory to assess the propensity of the scaffold to be permeated
      by blood vessels. In the review, it will be shown how X-ray microtomography
      (micro-CT) can give fundamental information regarding all the three aspects
      outlined above.

PMID- 22456011
TI  - Variability of morphometric parameters of human trabecular tissue from coxo
      arthritis and osteoporotic samples.
AB  - Morphometric and architectural bone parameters change in diseases such as
      osteoarthritis and osteoporosis.  The mechanical strength of bone is primarily
      influenced by bone quantity and quality. Bone quality is defined by parameters
      such as trabecular thickness, trabecular separation, trabecular density and
      degree of anisotropy that describe the micro-architectural structure of bone. 
      Recently, many studies have validated microtomography as a valuable investigative
      technique to assess bone morphometry, thanks to micro-CT non-destructive,  non
      invasive and reliability features, in comparison to traditional techniques such
      as histology. The aim of this study is the analysis by micro-computed tomography
      of six specimens, extracted from patients affected by osteoarthritis and
      osteoporosis, in order to observe the tridimensional structure and calculate
      several morphometric parameters.

PMID- 22456012
TI  - Present and future in the use of micro-CT  scanner 3D analysis for the study of
      dental and root canal morphology.
AB  - The goal of the present article is to illustrate and analyze the applications and
      the potential of microcomputed tomography (micro-CT) in the analysis of tooth
      anatomy and root canal morphology. The authors performed a micro-CT analysis of
      the following different teeth: maxillary first molars with a second canal in the
      mesiobuccal (MB) root, mandibular first molars with complex anatomy in the mesial
      root, premolars with single and double roots and with complicated apical anatomy.
      The hardware device used in this study was a desktop X-ray microfocus CT scanner
      (SkyScan 1072, SkyScan bvba, Aartselaar, Belgium). A specific software ResolveRT
      Amira (Visage Imaging) was used for the 3D analysis and imaging. The authors
      obtained three-dimensional images from 15 teeth. It was possible to precisely
      visualize and analyze external and internal anatomy of teeth, showing the finest
      details. Among the 5 upper molars analyzed, in three cases, the MB canals joined
      into one canal, while in the other two molars the two mesial canals were
      separate. Among the lower molars two of the five samples exhibited a single canal
      in the mesial root, which had a broad, flat appearance in a mesiodistal
      dimension. In the five premolar teeth, the canals were independent; however, the
      apical delta and ramifications of the root canals were quite complex. Micro-CT
      offers a simple and reproducible technique for 3D noninvasive assessment of the
      anatomy of root canal systems.

PMID- 22456013
TI  - Analysis of single point and continuous  wave of condensation root filling
      techniques by micro-computed tomography.
AB  - The aim of the present microtomographic study was to investigate the quality of
      root canal filling and the voids formation in canals of extracted teeth
      instrumented with a simultaneous technique and filled with two different methods.
      Twenty-four single-rooted teeth were assigned to two experimental groups (no. =
      12); canals were shaped with NiTi rotary files, irrigated with NaOCl and filled
      either with the single point (group 1) or the continuous wave of condensation
      technique (group 2). Specimens underwent microtomographic scanning. Collected
      data were statistically analyzed by nonparametric methods. Void mean percentages
      were found to be limited and similar between the two groups; the single point
      technique led to greater sealer thickness in partially oval canals.

PMID- 22456014
TI  - A new software for dimensional measurements in 3D endodontic root canal
      instrumentation.
AB  - The main issue to be faced to get size estimates of 3D modification of the dental
      canal after endodontic treatment is the co-registration of the image stacks
      obtained through micro computed tomography (micro-CT) scans before and after
      treatment. Here quantitative analysis of micro-CT images have been performed by
      means of new dedicated software targeted to the analysis of root canal after
      endodontic instrumentation. This software analytically calculates the best
      superposition between the pre and post structures using the inertia tensor of the
      tooth. This strategy avoid minimization procedures, which can be user dependent,
      and time consuming. Once the co-registration have been achieved dimensional
      measurements have then been performed by contemporary evaluation of quantitative
      parameters over the two superimposed stacks of micro-CT images. The software
      automatically calculated the changes of volume, surface and symmetry axes in 3D
      occurring after the instrumentation. The calculation is based on direct
      comparison of the canal and canal branches selected by the user on the pre
      treatment image stack.

PMID- 22456015
TI  - Comparative evaluation of cone-beam CT equipment with micro-CT in the
      visualization of root canal system.
AB  - The aim of this study was to compare three different cone-beam CT (CBCT)
      instruments used in dental clinical practice with micro-CT as gold standard.
      Three female monkeys' (Macaca fascicularis) skulls were selected and scanned by
      the tested CBCT-s. The most apical visible root canal level on the CBCT images
      was used as reference level (RL). After the image acquisition by CBCT-s dental
      jaw sections were scanned by micro-CT at a resolution of 17 um. Out of the left
      second and third molars 25 root canals were selected and analysed by three
      observers at RL and following cross sectional parameters were determined: area of
      the lumen, major and minor diameters, aspect ratio and mean thickness. Results
      suggest that only high resolution CBCT instruments allow dentists detecting the
      full length of the root canal.

PMID- 22456016
TI  - Fixture-abutment connection surface  and micro-gap measurements by 3D micro
      tomographic technique analysis.
AB  - X-ray micro-tomography (micro-CT) is a miniaturized form of conventional computed
      axial tomography (CAT) able to investigate small radio-opaque objects at a-few
      microns high resolution, in a non-destructive, non-invasive, and tri-dimensional
      way. Compared to traditional optical and electron microscopy techniques, which
      provide two-dimensional images, this innovative investigation technology enables
      a sample tri-dimensional analysis without cutting, coating or exposing the object
      to any particular chemical treatment. X-ray micro-tomography matches ideal 3D
      microscopy features: the possibility of investigating an object in natural
      conditions and without any preparation or alteration; non-invasive, non
      destructive, and sufficiently magnified 3D reconstruction; reliable measurement
      of numeric data of the internal structure (morphology, structure and ultra
      structure). Hence, this technique has multi-fold applications in a wide range of
      fields, not only in medical and odontostomatologic areas, but also in biomedical
      engineering, materials science, biology, electronics, geology, archaeology, oil
      industry, and semi-conductors industry. This study shows possible applications of
      micro-CT in dental implantology to analyze 3D micro-features of dental implant to
      abutment interface. Indeed, implant-abutment misfit is known to increase
      mechanical stress on connection structures and surrounding bone tissue. This
      condition may cause not only screw preload loss or screw fracture, but also
      biological issues in peri-implant tissues.

PMID- 22456017
TI  - Microtomographic and morphometric  characterization of a bioceramic bone
      substitute in dental implantology.
AB  - In recent years, bone tissue regeneration studies have led to a deeper knowledge
      of chemical and structural features of the best biomaterials to be used as
      replacements for lost bone structures, with the autologus bone still today the
      only graft material able to ostegenerate, osteinduct and/or osteoconduct. The
      difficulties of the small available amount of autologus bone, together with
      morbidity of a second surgical operation on the same patient, have been overcome
      using both synthetic and biologic substitute bones. The possibility of
      investigating morphometric characteristics of substitute bones makes it possible
      to evaluate the predictability of regenerative processes and, so far, a range of
      different methods have been used for the purpose. X-ray microtomography (micro
      CT) is a miniaturized form of conventional tomography, able to analyze the
      internal structure of small objects, performing three-dimensional images with
      high spatial resolution (< 10 micron pixel size). For a correct analysis, samples
      need not be altered or treated in any way, as micro-CT is a non-invasive and non
      destructive technique. It shows promising results in biomaterial studies and
      tissue engineering. This work shows the potential applications of this
      microtomographic technique by means of an in vitro analysis system, in
      characterizing morphometric features of human bone tissue, and contributes to the
      use of this technique in studies concerning biomaterials and bioscaffolds
      inserted in bone tissue.

PMID- 22456018
TI  - Microtomography evaluation of dental tissue wear surface induced by in vitro
      simulated chewing cycles on human and composite teeth.
AB  - In this study a 3D microtomography display of tooth surfaces after in vitro
      dental wear tests has been obtained.  Natural teeth have been compared with
      prosthetic teeth, manufactured by three different polyceramic composite
      materials.  The prosthetic dental element samples, similar to molars, have been
      placed in opposition to human teeth extracted by paradontology diseases.  After
      microtomography analysis, samples have been subjected to in vitro fatigue test
      cycles by servo-hydraulic mechanical testing machine.  After the fatigue test,
      each sample has been subjected again to microtomography analysis to obtain
      volumetric value changes and dental wear surface images.  Wear surface images
      were obtained by 3D reconstruction software and volumetric value changes were
      measured by CT analyser software.  The aim of this work has been to show the
      potential of microtomography technique to display very clear and reliable wear
      surface images.  Microtomography analysis methods to evaluate volumetric value
      changes have been used to quantify dental tissue and composite material wear.

PMID- 22456019
TI  - The application of X-ray microtomography for the assessement of root resorption
      caused by the orthodontic treatment of premolars.
AB  - The purpose of this study was to demonstrate potential application of micro
      computed tomography in the morphometric analysis of the root resorption in
      extracted human first premolars subjected to the orthodontic force. In one
      patient treated in the orthodontic clinic two mandibular first premolars
      subjected to orthodontic force for 4 weeks and one control tooth were selected
      for micro-computed tomographic analysis. The hardware device used in this study
      was a desktop X-ray microfocus CT scanner (SkyScan 1072). The morphology of
      root's surfaces was assessed by TView and Computer Tomography Analyzer (CTAn)
      softwares (SkyScan, bvba) which allowed analysis of all microscans,
      identification of root resorption craters and measurement of their length, width
      and volume. Microscans showed in details the surface morphology of the
      investigated teeth. The analysis of microscans allowed to detect 3 root
      resorption cavities in each of the orthodontically moved tooth and only one
      resorption crater in the control tooth. The volumes of the resorption craters in
      orthodontically-treated teeth were much larger than in a control tooth. Micro
      computed tomography is a reproducible technique for the three-dimensional non
      invasive assessment of root's morphology ex vivo. TView and CTan softwares are
      useful in accurate morphometric measurements of root's resorption.

PMID- 22456020
TI  - Micro-CT examination of human bone: from biopsies towards the entire organ.
AB  - Micro-CT systems are available that facilitate ex vivo examinations of human
      specimens as big as entire vertebrae, with spatial resolutions in the 10
      micrometer range. This opens a new way for looking at entire bones in 3D.
      Accurate description of the internal microarchitecture of the entire organ can be
      obtained, at spatial resolutions previously achievable only on excised biopsies.
      These high resolution scans produce large datasets and come with costs and
      benefits, which have to be considered in the successful planning of an
      experiment. The aim of this paper is to present examples of human vertebrae
      scanned at high resolution (17 um/pixel), allowing the visualization and
      quantification of the microarchitecture, and to discuss some aspects of using
      high resolution scans of such large specimens. The datasets were down-sampled to
      34 um and 68 um pixel size, and their morphometric parameters compared to those
      obtained at 17 um pixel size, in relation to data size and calculation time.

PMID- 22456021
TI  - A proposal of microtomography evaluation for restoration interface gaps.
AB  - Nowadays, several adhesive systems are used in dental restoration and they are
      evaluated by clinical research. In vitro evaluations are often made by means of
      traditional observation techniques (for example scanning electron microscope
      (SEM), while 3D cone-beam microtomography technique (3D micro-CT), that can be
      able to generate 3D sample images without any sample treatment during acquisition
      data, is going to be used a lot in the next few years. In dental cavity restored
      with composite, it is possible to predict the presence of gaps due to
      polymerization shrinkage; that is the reason this work purpose is to reveal by 3D
      images and measure by micro-CT analysis the voids generated applying the most
      used adhesive systems at the moment. By means of microtomographic analysis is
      proposed an aid to overcome bidimensional SEM investigation limits like random
      observation of sample surface, sample sectioning (to see inside it with the
      relative possible structural alterations induced on the same sample) and the gold
      sputtering treatment. For this experimental work, human crown teeth have been
      selected, all restored with the same composite material, using five adhesive
      systems. After about 48 hours each tooth has been acquired by means of Skyscan
      1072 micro-CT instrument and then processed by 3D reconstruction and micro-CT
      analyser software. Three adhesive systems have showed 3D micro-CT images with not
      as much voids as expected, with a very little extent. This kind of micro-CT in
      vitro evaluation proposal suggests a method to observe and quantify the voids
      generated after polymerization shrinkage during tooth restoration.

PMID- 22456022
TI  - Primary empty sella and GH deficiency: prevalence and clinical implications.
AB  - Primary empty sella (PES) is a particular anatomical condition characterized by
      the herniation of liquor within the sella turcica. The pathogenesis of this
      alteration, frequently observed in general population, is not yet completely
      understood. Recently reports demonstrated, in these patients, that hormonal
      pituitary dysfunctions, specially growth hormone (GH)/insulin- like growth factor
      (IGF-I) axis ones, could be relevant. The aim of this paper is to evaluate GH/IGF
      I axis in a group of adult patients affected by PES and to verify its clinical
      relevance. We studied a population of 28 patients with a diagnosis of PES. In
      each patient we performed a basal study of thyroid, adrenal and gonadal -
      pituitary axis and a dynamic evaluation of GH/IGF-I after GH-releasing hormone
      (GHRH) plus arginine stimulation test. To evaluate the clinical significance of
      GH/IGF-I axis dysfunction we performed a metabolic and bone status evaluation in
      every patients. We found the presence of GH deficit in 11 patients (39.2%). The
      group that displayed a GH/IGF-I axis dysfunction showed an impairment in
      metabolic profile and bone densitometry. This study confirms the necessity to
      screen the pituitary function in patients affected by PES and above all GH/IGF-I
      axis. Moreover the presence of GH deficiency could be clinically significant.

PMID- 22456023
TI  - Stray dog and cat laws and enforcement in Czech Republic and in Italy.
AB  - The growing numbers of stray dogs and cats have posed serious public-health,
      socioeconomic, political and animal-welfare problems in many EU countries. Stray
      animal population control is a complex issue and there are no easy solutions.
      Recognising the importance of the issue the European Commission has, since 2007,
      actively contributed to the elaboration of the first global welfare standards for
      the control of dog populations in the framework of the World Organisation for
      Animal Health (OIE). Problem-solving approaches vary in different countries as
      there is no common European Community legislation dealing with stray animal
      control. In this paper the authors describe the characteristics of the stray dog
      and cat problem in general and focus on existing European legislation. A
      comparative overview of policies and measures in place in the Czech Republic and
      in Italy is made to observe the differences between the two countries and
      understand the different needs in each, considering their historical and social
      differences (i.e. a post-communist eastern country vs a western country and
      founder member of what is now the European Union).

PMID- 22456024
TI  - Oscillococcinum for influenza treatment.
AB  - The use of a complementary medicine approach, and specifically of the popular
      medicine Oscillococcinum, for the treatment of influenza-like syndromes remains
      controversial. This brief paper analyses the currently available literature on
      this homeopathic preparation and the Cochrane Collaboration's 2006 systematic
      review, along with other recent studies, in order to clarify certain fundamental
      aspects of its use in the treatment of influenza. In the light of the reported
      findings, and applying the rigorous criteria of evidence-based medicine, we
      suggest that this medicine should be placed in category "BI".

PMID- 22456025
TI  - The impact of anemia on long-term clinical outcome in patients undergoing
      revascularization with the unrestricted use of drug-eluting stents.
AB  - BACKGROUND: Anemia is frequent among patients with cardiovascular disease and
      adversely affects prognosis. The objective of this analysis was to assess the
      impact of anemia on long-term clinical outcomes among patients undergoing
      percutaneous coronary intervention (PCI) with the unrestricted use of drug
      eluting stents (DES). METHODS AND RESULTS: Between April 2002 to March 2009, 6528
      consecutive patients underwent PCI with the unrestricted use of DES. Among
      patients with anemia according to the criteria by the World Health Organization
      (WHO) (hemoglobin <130 g/L for men and <120 g/L for women, respectively) patients
      below the 25(th) percentile separately for men and women were defined to have
      severe anemia. We compared clinical outcomes among patients with severe anemia
      and no/mild anemia during long-term follow-up through 4 years. Whereas 21.6% of
      patients were found to have anemia according to the WHO definition, 347 patients
      (5.5%) had severe anemia (mean hemoglobin, 98+/-11 g/L). Severe anemia was more
      prevalent among the elderly (P<0.001), diabetics (P<0.001), and patients with
      chronic kidney disease (P<0.001). In adjusted analyses, severe anemia was
      associated with an increased risk of death (hazard ratio, 1.86; 95% confidence
      interval, 1.37-2.52; P<0.0001), cardiac death (hazard ratio, 2.32; 95% confidence
      interval, 1.57-3.43; P<0.0001), and myocardial infarction (hazard ratio, 2.02;
      95% confidence interval, 1.36-3.01; P=0.00054) as compared with no/mild anemia
      without significant interaction across sexes (P=0.86) and acute coronary
      syndromes (P=0.61) and a trend toward a particularly high risk of mortality among
      anemic patients <65 years of age (P=0.07). Severe anemia resulted in a greater
      risk of overall definite stent thrombosis (hazard ratio, 2.59; 95% confidence
      interval, 1.48-4.54; P=0.00089). CONCLUSIONS: Severe anemia is common among
      patients undergoing PCI with the unrestricted use of DES and adversely affects
      long-term prognosis, including survival.

PMID- 22456026
TI  - Impact of frequency-domain optical coherence tomography guidance for optimal
      coronary stent implantation in comparison with intravascular ultrasound guidance.
AB  - BACKGROUND: Frequency-domain optical coherence tomography (FD-OCT) is a novel,
      high resolution intravascular imaging modality. Intravascular ultrasound (IVUS)
      is a widely used conventional imaging modality for achieving optimal stent
      deployment. The aim of this study was to evaluate the impact of FD-OCT guidance
      for coronary stent implantation compared with IVUS guidance. METHODS AND RESULTS:
      A total of 70 patients with de novo coronary artery lesions and either unstable
      or stable angina pectoris were enrolled in this randomized study (optical
      coherence tomography [OCT] group: n=35, IVUS group: n=35). In the OCT group,
      stent implantation was performed under FD-OCT guidance alone and final stent
      expansion was evaluated by IVUS. In the IVUS group, conventional IVUS guidance
      was used and final stent apposition was evaluated by FD-OCT. There were no
      significant differences regarding the procedural, fluoroscopy time, and contrast
      volume. Although device and clinical success rates also were similar, the
      visibility of vessel border was significantly lower in the OCT group (P<0.05).
      Minimum and mean stent area and focal and diffuse stent expansion were smaller
      (6.1+/-2.2 mm versus 7.1+/-2.1 mm, 7.5+/-2.5 versus 8.7+/-2.4 mm, 64.7+/-13.7%
      versus 80.3+/-13.4%, 84.2+/-15.8% versus 98.8+/-16.5%, P<0.05, respectively), and
      the frequency of significant residual reference segment stenosis at the proximal
      edge was higher in the OCT group (P<0.05). Incomplete apposed struts in both
      groups were similar (P=0.34). CONCLUSIONS: FD-OCT guidance for stent implantation
      was associated with smaller stent expansion and more frequent significant
      residual reference segment stenosis compared with conventional IVUS guidance.

PMID- 22456027
TI  - Outcomes after coronary stent implantation in patients with metal allergy.
AB  - BACKGROUND: Clinical outcomes after stent placement in patients with a history of
      metal allergy remain incompletely understood. We performed a single-center
      retrospective study to evaluate such outcomes. METHODS AND RESULTS: Twenty-nine
      allergic patients who underwent coronary stent implantation were compared with a
      nonallergic group (n=250) matched for demographics and a propensity score for
      allergy to metal. Hypersensitivity to nickel was reported in 26 of 29 and
      chromium in 9 of 29. Patch testing performed in 11 of 29 patients was positive in
      all. Comparing allergy versus control subjects, there were no differences in
      number of segments treated (1.4+/-0.7 versus 1.5+/-0.7), stents placed (1.7+/-1.1
      versus 1.6+/-0.9), and frequency of drug-eluting stent usage (52% versus 60%). In
      hospital death (0% versus 0%), myocardial infarction (MI, 4% versus 3%, P=0.27),
      and 30-day death (3% versus 0%, P=0.53) and MI (3% versus 4%, P=0.71) were
      statistically similar. There were no differences in 4-year death (12% versus
      13%), target lesion revascularization (TLR, 13 versus 17%, P=0.54), or
      death/MI/TLR (24% versus 34%, P=0.20). Clinically driven repeat angiography in 12
      of 29 allergy patients revealed binary restenosis rates of 27% in bare metal
      stents and 0% in drug-eluting stents, with mean diameter in-stent restenosis of
      36% and 8%, respectively. There was no change in circulating eosinophil and
      lymphocyte counts after stenting in the allergy group (0.19-0.20, P=0.67, and
      1.90-1.79, P=0.59, respectively). CONCLUSIONS: A history of metal allergy was not
      associated with adverse early or late outcomes in this single-center study.

PMID- 22456028
TI  - Evaluation of tumor extent in breast cancer patients using real-time MR navigated
      ultrasound: preliminary study.
AB  - OBJECTIVES: To evaluate the accuracy of real-time MR navigated ultrasound (MRnav
      US) for tumor extent measurements in breast cancer and to investigate variables
      influencing the accuracy of MRnav US in comparison with US alone. METHODS: Fifty
      three patients with 60 malignancies underwent preoperative breast MRI and US with
      or without MRI navigation. Maximum lesion sizes based on MRnav US and US alone
      were measured, and their relationship with the pathology was analyzed considering
      the differences in the clinicopathologic variables of the patients. RESULTS:
      Among 60 breast cancers, mean lesion size at initial breast US without MRI
      navigation and at MRI-navigated US was 19 mm and 24 mm, respectively, compared
      with 28 mm on the histopathology. Overall, the tumor size estimated with MRnav US
      was more strongly correlated with the histologic tumor size than with US alone.
      Accurate measurements by MRnav US were significantly more frequent in the lesions
      that were presented as a mass type on MRI. In addition, the accurate measurement
      of mass extent was improved with MRnav US in patients who had non-mass type
      lesions on MRI and who had undergone neoadjuvant systemic chemotherapy when
      compared with US alone. CONCLUSION: MRnav US was more accurate for tumor extent
      estimation than US alone, and specific clinicopathologic variables can affect the
      accuracy of MRnav US.

PMID- 22456029
TI  - Prospective evaluation of early follicular ovarian stromal blood flow in
      infertile women undergoing IVF-ET treatment.
AB  - BACKGROUND: To evaluate the role of early follicular stromal flow studies in
      predicting ovarian response during IVF-ET treatment and to assess their
      correlation with ovarian reserve parameters and clinical pregnancy achievement.
      MATERIALS & METHODS: One hundred and sixty-eight consecutive and unselected
      infertile women undergoing their first IVF-ET treatment were included in the
      study. Basal ovarian reserve and stromal Doppler flow studies were performed in a
      natural cycle before starting treatment. Four Doppler indices were measured; peak
      systolic velocity (PSV), pulsatility index (PI), resistance index (RI) and
      systole/diastole ratio (S/D). Following completion of IVF-ET treatment Pearson's
      correlation analysis was performed to examine the correlation between Doppler
      indices, ovarian response, basal ovarian reserve parameters and clinical
      pregnancy achievement. RESULTS: A positive correlation was found between the
      number of >=14 mm follicles on hCG day and PSV. The number of >=14 mm follicles
      and retrieved oocytes had a significant negative correlation with RI and S/D
      ratio. As well, the number of fertilized oocytes had a significant negative
      correlation with S/D ratio. Absence of a Doppler signal in one or both ovaries
      was significantly higher in the women with poor response (31%) as compared to
      women with normal response (16%). In addition, RI correlated positively with
      basal FSH as well as FSH/LH ratio and negatively with AFC. The S/D ratio had a
      negative correlation with AFC (p = 0.027). A significant positive correlation
      between PSV, total ovarian volume (p = 0.011) and mean ovarian volume (p = 0.019)
      was detected. However, no correlation between all four Doppler indices and age
      was detected. Moreover, Doppler indices did not differ significantly between
      conception and non-conception cycles following IVF-ET treatment. CONCLUSIONS:
      Early follicular stromal Doppler signals is correlated with ovarian response as
      well as basal ovarian reserve parameters, but have no correlation with age
      neither with clinical pregnancy achievement in infertile women undergoing IVF-ET
      treatment.

PMID- 22456030
TI  - Gorham-Stout disease and cerebrospinal fluid otorrhea.
AB  - OBJECTIVE AND IMPORTANCE: Gorham-Stout disease is a rare entity characterized by
      vascular proliferation causing local destruction of bone tissue. Owing to its low
      incidence and variable clinical presentation, the diagnosis requires a high
      degree of awareness by the clinician. CLINICAL PRESENTATION: We present the case
      of a 2-year-old boy diagnosed of Gorham-Stout syndrome with involvement of the
      temporal bone and secondary cerebrospinal fluid (CSF) leakage. INTERVENTION:
      Because of the CSF leakage, the patient required two surgical interventions. The
      second intervention included mastectomy and placement of a patch and a lumbar
      drainage device during 50 days, after which the leakage ceased. CONCLUSION:
      Gorham-Stout disease is a rare condition that can affect the skull base and even
      present with CSF leakage.

PMID- 22456031
TI  - Hereditary and acquired complement component 1 esterase inhibitor deficiency: a
      review for the hematologist.
AB  - Hereditary angioedema (HAE), a rare autosomal dominant disorder, was first
      described in the late 19th century. The disease remained poorly understood and
      without therapeutic options until the latter half of the 20th century. Advances
      in the understanding of immunologic and hematologic pathways have shed light on
      HAE, a disease characterized by painful and unpredictable recurrent attacks of
      nonpitting edema without urticaria. Recognition that a deficiency of complement
      component 1 (C1) esterase inhibitor leads to overproduction of vasoactive kinins
      that cause angioedema paved the way for the development of early treatments.
      Increased understanding of the role of bradykinin in hereditary and acquired
      forms of C1 esterase inhibitor deficiency has led to the development of more
      targeted treatments for this painful, debilitating and potentially life
      threatening disease.

PMID- 22456032
TI  - An inter-laboratory study to determine the effectiveness of procedures for
      discriminating amphibole asbestos fibers from amphibole cleavage fragments in
      fiber counting by phase-contrast microscopy.
AB  - The US Occupational Safety and Health Administration (OSHA) and Mine Safety and
      Health Administration do not regulate cleavage fragments of amphibole and
      serpentine minerals as asbestos, even when particles meet the dimensional
      criteria for counting under standard phase-contrast microscopy methods. The OSHA
      ID-160 method cautions that discriminatory counting is difficult and should not
      be attempted unless necessary and no procedure is provided for differentiation. A
      standard published by the American Society for Testing and Materials (ASTM
      International D7200-06) includes an attempt to codify a procedure but recognizes
      that the procedure should be validated in an inter-laboratory study. The US
      National Institute for Occupational Safety and Health has carried out such a
      study with multiple laboratories using slides made from riebeckite and
      crocidolite, grunerite and amosite, tremolite and tremolite asbestos, and
      actinolite and actinolite asbestos using two different measurement aids
      (graticules). The asbestos fibers had dimensions consistent with those reported
      for air samples from actual amphibole asbestos operations, and the cleavage
      fragments were also dimensionally consistent with those found in non-asbestos
      mining and milling operations. The procedure for discriminating asbestos fibers
      from other mineral particles in the ASTM Standard calls for the recognition of
      characteristics supposedly common to asbestos. For the asbestos fibers created in
      this study, these characteristics were found not to be common and generally a
      function of length. More importantly, different laboratories did not recognize
      these features consistently. Laboratories were much more consistent in measuring
      dimensions, but excessive overlap in the lengths of asbestos fibers and cleavage
      fragments rendered length a poor criterion for discrimination. The ASTM
      discrimination procedure as written could not be supported on the basis of this
      study. Width was a much more consistent parameter for distinguishing the asbestos
      and non-asbestos fibers in this study and inclusion of aspect ratio, while
      considered important by some researchers, did not refine the discrimination
      further. The ability of the majority of microscopists in this study to
      discriminate fibers and cleavage fragments through measurement of particle widths
      was determined and found to be within limits of uncertainty typical for air
      sampling measurements. A width criterion might be a very simple and useful aid
      where discrimination between asbestos and non-asbestos fibers in fiber counting
      by phase-contrast microscopy is required for further investigation. Recognition
      of asbestos features can also be retained as excessive recognition by some
      laboratories will lead to a conservative decision for additional investigation.

PMID- 22456033
TI  - Congenital deafness in Jack Russell terriers: prevalence and association with
      phenotype.
AB  - Congenital hereditary sensorineural deafness is the most common form of deafness
      in dogs. The objectives of this study were to determine a reliable measure of the
      prevalence of deafness in Jack Russell terriers, an affected breed, and
      associations between deafness and phenotypic characteristics. Brainstem auditory
      evoked response recordings and phenotypic parameters (coat color, coat texture,
      sex, eye color, sire and dam hearing status) were recorded for 1009 Jack Russell
      terriers. The prevalence of unilateral and bilateral deafness was 3.57% and
      0.50%, respectively, lower by a factor of three to four than in earlier reports
      based on smaller and closely related kindreds. Significant association with
      deafness was identified with white coat color and parental hearing status, but
      not with sex or coat type. Lack of significant sex or coat type associations and
      the significant association with white coat color are consistent with previous
      reports. In conclusion the prevalence of deafness in Jack Russell terriers is
      lower than initially reported. Deafness was associated with white coat color and
      parental hearing status. The association with parental hearing status supports
      this form of deafness being a heritable trait in the breed and the association
      with white coat color supports an inheritance linked to pigmentation genes.

PMID- 22456035
TI  - Preterm birth in the Inuit and First Nations populations of Quebec, Canada, 1981
      2008.
AB  - OBJECTIVES: To evaluate preterm birth (PTB) for Inuit and First Nations vs. non
      Indigenous populations in the province of Quebec, Canada. STUDY DESIGN:
      Retrospective cohort study. METHODS: We evaluated singleton live births for
      Quebec residents, 1981-2008 (n = 2,310,466). Municipality of residence (Inuit
      inhabited, First Nations-inhabited, rest of Quebec) and language (Inuit, First
      Nations, French/English) were used to identify Inuit and First Nations births.
      The outcome was PTB (<37 completed weeks). Cox proportional hazards regression
      was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) of
      PTB, adjusting for maternal age, education, marital status, parity and birth
      year. RESULTS: PTB rates were higher for Inuit language speakers in Inuit
      inhabited areas and the rest of Quebec compared with French/English speakers in
      the rest of Quebec, and disparities persisted over time. Relative to
      French/English speakers in the rest of Quebec, Inuit language speakers in the
      rest of Quebec had the highest risk of PTB (HR 1.98, 95% CI: 1.62-2.41). The risk
      was also elevated for Inuit language speakers in Inuit-inhabited areas, though to
      a lesser extent (HR 1.29, 95% CI: 1.18-1.41). In contrast, First Nations language
      speakers in First Nations-inhabited areas and the rest of Quebec had similar or
      lower risks of PTB relative to French/English speakers in the rest of Quebec.
      CONCLUSIONS: Inuit populations, especially those outside Inuit-inhabited areas,
      have persistently elevated risks of PTB, indicating a need for strategies to
      prevent PTB in this population.

PMID- 22456036
TI  - Physical activity and fitness in 8-year-old overweight and normal weight children
      and their parents.
AB  - OBJECTIVES: To compare the physical fitness and physical activity of 8-year-old
      overweight children (n = 53) to normal weight children (n = 65), and to determine
      whether a significant relationship exists between physical activity of parents
      and their children. STUDY DESIGN: A cross-sectional study. METHODS: A total of
      119 children from Northern Finland were recruited for the study. Waist
      circumference, height, weight and BMI were measured. Physical activity of the
      children and their parents was determined with self-administered 7-day recall
      questionnaires (PAQ-C). Physical fitness of the children was evaluated with 7
      items of the EUROFIT-test battery (flamingo balance test, plate tapping, sit-and
      reach test, sit-ups, bent arm hang and 10*5 shuttle run). Aerobic capacity of the
      children was tested with 6-minute walking test. RESULTS: Overweigh was related to
      impaired performance in tests requiring muscle endurance, balance, explosive
      power of lower extremities, upper body strength and endurance, speed and agility
      in both genders and aerobic capacity in boys. Physical activity levels of
      overweight boys (2.41 SD 0.72) were lower than their lean counterparts (2.91 SD
      0.64, p = 0.004); no such difference was observed in girls (2.53 SD 0.64 vs. 2.59
      SD 0.68, p = 0.741). Physical activity was significantly associated with better
      performance in several physical fitness tests in boys, but not in girls. Mothers'
      physical activity was associated with children's physical activity (r = 0.363, p
      < 0.001), but no such association was found between fathers and children (r =
      0.019, p = 0.864). CONCLUSION: This study shows an inverse relationship between
      excess bodyweight and physical fitness in children. Mother-child relationship of
      physical activity appeared to be stronger than father-child relationship.
      Improving physical fitness in children through physical activity might require
      interventions that are responsive to the ability and needs of overweight children
      and their families and focus on helping parents and children to be physically
      active together.

PMID- 22456037
TI  - Health consumption in Sami speaking municipalities and a control group with
      regard to medical imaging.
AB  - OBJECTIVES: The Northern Norway Regional Health Authority trust aims to offer a
      high quality specialist health care to all inhabitants. The objective of this
      study was to document the consumption of medical imaging [conventional
      radiography (CR), computerised tomography (CT), magnetic resonance (MR),
      ultrasound (US)]. METHODS: The eight municipalities in northern Norway included
      in the administration area of the Sami language law (Sami group - 132,490
      persons/year in the period 2003-2009, mean/year 19,363 inhabitants) were matched
      with a control group of 11 municipalities (non-Sami group - 135,539 persons/year,
      mean/year 18,927 inhabitants). Population data was accessed from Statistics
      Norway. Data on imaging exams were derived from a regional database including
      production data from all public and private institutions within the region. All
      four main modality groups (CR, CT, MR, US) were analysed. Variations for imaging
      frequency on each modality were compared between the Sami and non-Sami
      municipalities. RESULTS: A total of 278,832 exams were performed during study
      period. The age adjusted exam rate (all modalities) was significantly higher (p <
      0.001) in non-Sami (females and males) group. There was no difference with regard
      to conventional radiography (CR) (p = 0.855). Whereas MR (p < 0.001) imaging was
      more common in the Sami group, CT (p < 0.001) and US (p = 0.003) exams were more
      frequently used in the control group. CONCLUSION: People living in Sami speaking
      communities experienced significantly less CT and US exams, but had more MR exams
      than the control group. A relatively high physical activity, obesity and a lower
      risk of cancer may be explanations.

PMID- 22456038
TI  - Occurrence of pancreatic, biliary tract, and gallbladder cancers in Alaska Native
      people, 1973-2007.
AB  - OBJECTIVES: To describe the occurrence of pancreatic, biliary tract, and
      gallbladder cancers within the Alaska Native (AN) population. STUDY DESIGN:
      Population-based analysis utilizing a tumor registry and comparative population
      data. METHODS: Pancreaticobiliary cancers rates for AN people during 1973-2007
      were determined from the Surveillance, Epidemiology, and End Results (SEER) AN
      Tumor Registry. Cancer incidence rates were age-adjusted to the World Standard
      Million and compared over 2 time periods with US white and black rates. RESULTS:
      During 1973-2007, 213 AN people developed pancreatic cancer, 73 gallbladder
      cancer and 61 biliary tract cancer. Pancreatic cancer occurs at similar rates in
      AN men and women, but data for 1993-2007 indicate that the rates among AN men may
      be increasing. The incidence rate in AN women (9.5/100,000) was statistically
      higher than in US white women (5.8/100,000). The incidence for biliary tract
      cancer in AN men and gallbladder cancer in AN men and women is statistically
      higher than that for US whites and blacks. CONCLUSIONS: Pancreaticobiliary
      cancers, particularly biliary tract and gallbladder cancers, in both AN men and
      women and pancreatic cancer in women occur at an increased rate in AN people.
      Risk factors relating to the elevated rate are discussed. Certain factors are
      potentially modifiable, such as the use of tobacco and obesity.

PMID- 22456040
TI  - Oral health in a First Nations and a non-Aboriginal population in Manitoba.
AB  - OBJECTIVES: To analyze the prevalence of poor oral health and selected
      determinants in First Nations (FN) and Caucasian samples in Manitoba, Canada.
      STUDY DESIGN: Cross-sectional survey, nested in a cohort study. METHODS: FN and
      Caucasian participants completed a questionnaire on socio-demographic variables,
      oral health symptoms, and oral health-related behaviours as part of a broader
      cohort study comparing these ethnic groups for different chronic immune mediated
      diseases. RESULTS: Caucasians reported higher levels of employment, education,
      and urban dwelling than FNs (p<0.001). FNs reported smoking more, and having
      poorer oral health-related behaviours than Caucasians (p<0.001). After adjustment
      for age and sex, FN reported having more oral health symptoms than Caucasians
      (odds ratio (OR): 2.71; 95% confidence interval (CI): 1.73, 4.52), but the
      association was reduced and not statistically significant after adjustment for
      other socio-demographic variables (OR=1.34; 95% CI: 0.58, 3.10). Oral health
      symptoms were associated with current smoking among FN (adjusted OR=2.67, 95% CI:
      1.05, 6.78). Oral hygiene behaviours were significantly related to smoking
      status, rural living and education for both groups. CONCLUSIONS: Oral health
      related behaviours and smoking were found to be significant factors explaining
      poor oral health, which were lower for the FNs cohort than the Caucasian sample.
      However oral health and related behaviours were less related to their ethnicity
      than to socio-demographic factors, suggesting that policies to change behaviour
      will not result in lasting reductions in oral health differences between these
      groups in Manitoba.

PMID- 22456039
TI  - Gender differences in comorbidity of conduct disorder among adolescents in
      Northern Finland.
AB  - OBJECTIVES: Conduct disorder (CD) refers to a pattern of severe antisocial and
      aggressive behaviour manifested in childhood or adolescence, with heavy costs to
      society. Though CD is a common psychiatric diagnosis among adolescents of both
      genders, gender differences in comorbidity of CD have been little studied. In
      this study we examined gender differences among adolescents with CD in causes for
      hospitalization, comorbid psychiatric diagnoses and somatic conditions. STUDY
      DESIGN: The original study sample consisted of 508 inpatient adolescents in
      Northern Finland (age 12-17); 155 of them (65 girls, 92 boys) fulfilled the DSM
      IV criteria for CD. METHODS: Diagnosis of CD and psychiatric comorbidities were
      obtained from the K-SADS-PL and somatic conditions from the EuropAsi. RESULTS: As
      compared to boys with CD, suicidality (including suicidal ideation and behaviour)
      was significantly more commonly the cause of hospitalization among girls with CD
      (43% vs. 24%, p=0.013). Among somatic conditions, there was a significant
      predominance in self-reported allergies among girls (60% vs. 25%, p<0.001). Girls
      had more often diagnosed comorbid post-traumatic stress disorder (13% vs. 3%,
      p=0.025) and marginally significantly more major depressive disorder (36% vs.
      23%, p=0.086). CONCLUSIONS: Girls with CD seem to have an increased tendency to
      develop both comorbid psychiatric and somatic conditions as well as suicidality.
      New clinical aspects in treatment of CD and comorbid disorders among girls are
      discussed.

PMID- 22456041
TI  - Dietary quality and adequacy among Aboriginal alcohol consumers in the Northwest
      Territories, Canada.
AB  - OBJECTIVES: The present study aimed to assess dietary adequacy and quality among
      Inuvialuit alcohol consumers and non-consumers in the Northwest Territories
      (NWT), Canada. STUDY DESIGN: Cross-sectional study. METHODS: A validated
      quantitative food frequency questionnaire was administered to individuals (n =
      216) of randomly selected households in 3 NWT communities to capture dietary
      intake and alcohol consumption over a 30-day recall period. The daily energy and
      nutrient intake, dietary adequacy and the top food sources of energy and selected
      nutrients were determined by alcohol consumption status. RESULTS: Energy intake
      was higher among all alcohol consumers regardless of gender. Male alcohol
      consumers had lower nutrient intake density (per 4,184 kJ) of protein,
      cholesterol and several micronutrients (p <= 0.05), and female alcohol consumers
      had lower intake density of saturated fat (p <= 0.01), thiamine, folate and
      sodium (p <= 0.05). Among all men and women, 70-100% had inadequate intakes of
      dietary fibre, vitamin E and potassium. Non-nutrient-dense foods contributed
      similar amounts and traditional foods (TF) contributed 3% less to energy
      comparing alcohol consumers to non-consumers. CONCLUSION: Nutrient inadequacies
      are prevalent among Aboriginal populations in the Canadian Arctic and may be
      exacerbated by alcohol consumption due to alcohol's effects on dietary intake,
      nutrient transport and metabolism. Adult Inuvialuit who consumed alcohol had
      increased caloric intake and consumed similar amounts of non-nutrient-dense foods
      and less nutrient-dense TF. Fewer dietary inadequacies were observed among
      alcohol consumers than non-consumers, which might be due to the increase in
      overall food intake among alcohol consumers; however, further exploration of
      volume and pattern of drinking might help explain this result.

PMID- 22456042
TI  - Design and methods in a survey of living conditions in the Arctic - the SLiCA
      study.
AB  - OBJECTIVES: The main objective of this study is to describe the methods and
      design of the survey of living conditions in the Arctic (SLiCA), relevant
      participation rates and the distribution of participants, as applicable to the
      survey data in Alaska, Greenland and Norway. This article briefly addresses
      possible selection bias in the data and also the ways to tackle it in future
      studies. STUDY DESIGN: Population-based cross-sectional survey. METHODS:
      Indigenous individuals aged 16 years and older, living in Greenland, Alaska and
      in traditional settlement areas in Norway, were invited to participate. Random
      sampling methods were applied in Alaska and Greenland, while non-probability
      sampling methods were applied in Norway. Data were collected in 3 periods: in
      Alaska, from January 2002 to February 2003; in Greenland, from December 2003 to
      August 2006; and in Norway, in 2003 and from June 2006 to June 2008. The
      principal method in SLiCA was standardised face-to-face interviews using a
      questionnaire. RESULTS: A total of 663, 1,197 and 445 individuals were
      interviewed in Alaska, Greenland and Norway, respectively. Very high overall
      participation rates of 83% were obtained in Greenland and Alaska, while a more
      conventional rate of 57% was achieved in Norway. A predominance of female
      respondents was obtained in Alaska. Overall, the Sami cohort is older than the
      cohorts from Greenland and Alaska. CONCLUSIONS: Preliminary assessments suggest
      that selection bias in the Sami sample is plausible but not a major threat. Few
      or no threats to validity are detected in the data from Alaska and Greenland.
      Despite different sampling and recruitment methods, and sociocultural
      differences, a unique database has been generated, which shall be used to explore
      relationships between health and other living conditions variables.

PMID- 22456043
TI  - Factors related to fruit, vegetable and traditional food consumption which may
      affect health among Alaska Native People in Western Alaska.
AB  - OBJECTIVES: Determine intake of fruits, vegetables and traditional foods (TF),
      availability of foods, and attitudes towards increasing their consumption. STUDY
      DESIGN: Establish community baseline through a cross-sectional sample of
      residents who were weighed, measured and interviewed. Village stores were
      surveyed for food availability, price and quality. METHODS: Eighty-eight
      respondents self-identified as the household member primarily responsible for
      food shopping and cooking were surveyed in 3 Western Alaska Native villages using
      a food frequency questionnaire, and village stores were evaluated using food
      environment surveys. RESULTS: Overweight (BMI[kg/m(2)] > 25) was present in 68%
      of participants. Fruit and vegetable intake (3.3 median servings/day) was low in
      comparison to recommended intakes of 5-9 servings/d. Seventy-two per cent were
      eating less than 5 servings/d of fruits and vegetables combined. Thirty-four per
      cent of respondents were trying to eat more vegetables; 41% were trying to eat
      more fruits. The median number of servings of TF was 3.2/d (mean 4.3/d). Seventy
      seven per cent of respondents reported that they ate enough TF. CONCLUSION:
      Recommendations to continue use of TF and increase intake of fruits and
      vegetables are consistent with local attitudes. Our findings indicate that
      increasing the availability of fruits and vegetables would be well received.
      Information from this study provides a basis for nutrition education and food
      supplement programs that is responsive to the needs and perceptions of the
      residents. Continued TF intake and increased fruit and vegetable intake have the
      potential to benefit the health of rural residents.

PMID- 22456044
TI  - Metabolic profile in two physically active Inuit groups consuming either a
      western or a traditional Inuit diet.
AB  - OBJECTIVES: To evaluate the effect of regular physical activity on metabolic risk
      factors and blood pressure in Inuit with high BMI consuming a western diet (high
      amount of saturated fatty acids and carbohydrates with a high glycemic index).
      STUDY DESIGN: Cross sectional study, comparing Inuit eating a western diet with
      Inuit eating a traditional diet. METHODS: Two physically active Greenland Inuit
      groups consuming different diet, 20 eating a traditional diet (Qaanaaq) and 15
      eating a western diet (TAB), age (mean (range)); 38, (22-58) yrs, BMI; 28 (20-40)
      were subjected to an oral glucose tolerance test (OGTT), blood sampling, maximal
      oxygen uptake test, food interview/collection and monitoring of physical
      activity. RESULTS: All Inuit had a normal OGTT. Fasting glucose (mmol/l), HbA1c
      (%), total cholesterol (mmol/l) and HDL-C (mmol/l) were for Qaanaaq women: 4.8+/
      0.2, 5.3+/-0.1, 4.96+/-0.42, 1.34+/-0.06, for Qaanaaq men: 4.9+/-0.1, 5.7+/-0.1,
      5.08+/-0.31, 1.28+/-0.09, for TAB women: 5.1+/-0.2, 5.3+/-0.1, 6.22+/-0.39,
      1.86+/-0.13, for TAB men: 5.1+/-0.2, 5.3+/-0.1, 6.23+/-0.15, 1.60+/-0.10. No
      differences were found in systolic or diastolic blood pressure between the
      groups. There was a more adverse distribution of small dense LDL-C particles and
      higher total cholesterol and HDL-C concentration in the western diet group.
      CONCLUSIONS: Diabetes or impaired glucose tolerance was not found in the Inuit
      consuming either the western or the traditional diet, and this could, at least
      partly, be due to the high amount of regular daily physical activity. However,
      when considering the total cardio vascular risk profile the Inuit consuming a
      western diet had a less healthy profile than the Inuit consuming a traditional
      diet.

PMID- 22456045
TI  - Heart rate is associated with markers of fatty acid desaturation: the GOCADAN
      study.
AB  - OBJECTIVES: To determine if heart rate (HR) is associated with desaturation
      indexes as HR is associated with arrhythmia and sudden death. STUDY DESIGN: A
      community based cross-sectional study of 1214 Alaskan Inuit. METHODS: Data of FA
      concentrations from plasma and red blood cell membranes from those >=35 years of
      age (n = 819) were compared to basal HR at the time of examination. Multiple
      linear regression with backward stepwise selection was employed to analyze the
      effect of the desaturase indexes on HR, after adjustment for relevant covariates.
      RESULTS: The Delta(5) desaturase index (Delta(5)-DI) measured in serum has
      recently been associated with a protective role for cardiovascular disease. This
      index measured here in plasma and red blood cells showed a negative correlation
      with HR. The plasma stearoyl-CoA-desaturase (SCD) index, previously determined to
      be related to cardiovascular disease (CVD) mortality, on the other hand, was
      positively associated with HR, while the Delta(6) desaturase index (Delta(6)-DI)
      had no significant effect on HR. CONCLUSION: Endogenous FA desaturation is
      associated with HR and thereby, in the case of SCD, possibly with arrhythmia and
      sudden death, which would at least partially explain the previously observed
      association between cardiovascular mortality and desaturase activity.

PMID- 22456046
TI  - A longitudinal study of the effect of Antarctic residence on energy dynamics and
      aerobic fitness.
AB  - OBJECTIVES: To investigate the effect of Antarctic residence on energy dynamics
      and aerobic fitness over the course of a year in over-wintering personnel. STUDY
      DESIGN: A prospective longitudinal observational study. METHODS: A convenience
      sample of personnel over-wintering at Rothera Research Station in Antarctica was
      studied. Body weight, body fat, food intake, activity and aerobic fitness were
      recorded every 30 days for 1 year. Body weight, body fat and food intake were
      measured using weighing scales, skinfold callipers and diet records,
      respectively; activity was measured using accelerometer-based activity trackers
      and aerobic fitness using a treadmill protocol. Climate markers of temperature
      and sunlight hours were also recorded. RESULTS: Twenty-one subjects took part in
      the study over the 12-month period. A statistically significant increase in body
      weight and body fat in winter was observed (p=0.012 and p=0.049, respectively).
      There were no statistically significant trends in activity, food intake or
      aerobic fitness. CONCLUSIONS: There were significant seasonal changes in body
      weight and body fat, with both measures increasing in winter but no significant
      changes in the other main outcome measures.

PMID- 22456047
TI  - Traditional food consumption behaviour and concern with environmental
      contaminants among Cree schoolchildren of the Mushkegowuk territory.
AB  - OBJECTIVES: To investigate factors influencing consumption of traditional foods
      (e.g. wild game, fish) and concerns about environmental contaminants among
      schoolchildren of the Mushkegowuk Territory First Nations (Moose Factory, Fort
      Albany, Kashechewan, Attawapiskat, and Peawanuck). STUDY DESIGN: Cross-sectional
      data collection from a Web-based Eating Behaviour Questionnaire (WEB-Q). METHODS:
      Schoolchildren in grades 6-12 (n = 262) responded to 4 of the WEB-Q questions:
      (a) Do you eat game? (b) How often do you eat game? (c) How concerned are you
      about the environmental contaminants in the wild game and fish that you eat? (d)
      I would eat more game if... [6 response options]. Data were collected in 2004
      (Fort Albany), 2005 (Peawanuck), 2006 (Attawapiskat), 2007 (Moose Factory) and
      2009 (Kashechewan). Hierarchical log-linear modelling (LLM) was used for analyses
      of multi-way frequency data. RESULTS: Of the schoolchildren answering the
      specific questions: 174 consumed game; 95 reported concerns about contaminants in
      game; and 84 would increase their game consumption if it were more available in
      their homes. LLM revealed significant differences between communities;
      schoolchildren in Moose Factory consumed game "rarely or never" at greater than
      expected frequency, and fewer than expected consumed game "at least once a day".
      Schoolchildren in Kashechewan had greater frequency of daily game consumption and
      few were concerned about contaminants in game. Using LLM, we found that sex was
      an insignificant variable and did not affect game consumption frequency or
      environmental contaminant concern. CONCLUSION: The consumption of traditional
      foods differed between communities and appears to be related to contamination
      concerns. In addition, latitudinal variation appears to influence the frequency
      of traditional food consumption in children; children in the most southerly
      location consumed traditional food less frequently.

PMID- 22456048
TI  - The impact of Action Schools! BC on the health of Aboriginal children and youth
      living in rural and remote communities in British Columbia.
AB  - OBJECTIVES: The aim of the study was to determine the short-term impact of a 7
      month whole-school physical activity and healthy eating intervention (Action
      Schools! BC) over the 2007-2008 school year for children and youth in 3 remote
      First Nations villages in northwestern British Columbia. STUDY DESIGN: A pre
      experimental pre/post design was conducted with 148 children and youth (77 males,
      71 females; age 12.5+/-2.2 yrs). METHODS: We evaluated changes in obesity (body
      mass index [wt/ht(2)] and waist circumference z-scores: zBMI and zWC), aerobic
      fitness (20-m shuttle run), physical activity (PA; physical activity
      questionnaire and accelerometry), healthy eating (dietary recall) and
      cardiovascular risk (CV risk). RESULTS: zBMI remained unchanged while zWC
      increased from 0.46+/-1.07 to 0.57+/-1.04 (p<0.05). No change was detected in PA
      or CV risk but aerobic fitness increased by 22% (25.4+/-15.8 to 30.9+/-20.0 laps;
      p<0.01). There was an increase in the variety of vegetables consumed (1.10+/-1.18
      to 1.45+/-1.24; p<0.05) but otherwise no dietary changes were detected.
      CONCLUSIONS: While no changes were seen in PA or overall CV risk, zWC increased,
      zBMI remained stable and aerobic fitness improved during a 7-month intervention.

PMID- 22456049
TI  - Level and temporal trend of perfluoroalkyl acids in Greenlandic Inuit.
AB  - OBJECTIVES: Perfluoroalkyl acids (PFAAs) have been detected in human blood,
      breast milk and umbilical cord blood across the globe. PFAAs do accumulate in the
      marine food chain in Arctic regions. In Greenland, increasing PFAA concentrations
      were observed during 1982-2006 in ringed seals and polar bears. However, until
      now, no data have been reported for PFAAs in Greenlandic Inuit. This study
      assesses the level and temporal trend of serum PFAAs in Greenlandic Inuit. STUDY
      DESIGN: Cross-section and temporal time trend survey. METHODS: Serum PFAA levels
      were determined in 284 Inuit from different Greenlandic districts using liquid
      chromatography-tandem mass spectrometry with electrospray ionization. The
      temporal time trend of serum PFAAs in Nuuk Inuit during 1998-2005 and the
      correlation between serum PFAAs and legacy persistent organic pollutants (POPs)
      were explored. RESULTS: Serum PFAA levels were higher in Nuuk Inuit than in non
      Nuuk Inuit. Within the same district, higher PFAA levels were observed for males.
      An age-dependent, increasing trend of serum PFAA levels in the period from 1998
      2005 was observed for Nuuk Inuit. For the pooled gender data, no significant
      association between PFAAs and legacy POPs was observed for Nuuk Inuit while for
      non-Nuuk Inuit this correlation was significant. No correlation between PFAAs and
      legacy POPs was found for male Inuit, whereas significant correlation was
      observed both for pooled female Inuit and for non-Nuuk Inuit females.
      CONCLUSIONS: We suggest that sources other than seafood intake might contribute
      to the observed higher PFAA levels in Nuuk Inuit compared to the pooled non-Nuuk
      Inuit.

PMID- 22456050
TI  - Inuit women's attitudes and experiences towards cervical cancer and prevention
      strategies in Nunavik, Quebec.
AB  - OBJECTIVES: To describe the attitudes about and experiences with cervical cancer,
      Pap smear screenings and the HPV vaccine among a sample of Inuit women from
      Nunavik, Quebec, Canada. We also evaluated demographic and social predictors of
      maternal interest in HPV vaccination. STUDY DESIGN: A mixed method design was
      used with a cross-sectional survey and focus group interviews. METHODS: Women
      were recruited through convenience sampling at 2 recruitment sites in Nunavik
      from March 2008 to June 2009. Differences in women's responses by age, education,
      and marital status were assessed. Unconditional logistic regression was used to
      determine predictors of women's interest in HPV vaccination for their children.
      RESULTS: Questionnaires were completed by 175 women aged 18-63, and of these
      women a total of 6 women aged 31-55 participated in 2 focus groups. Almost half
      the survey participants had heard of cervical cancer. Women often reported
      feelings of embarrassment and pain during the Pap smear and older women were more
      likely to feel embarrassed than younger women. Only 27% of women had heard of the
      HPV vaccine, and 72% of these women were interested in vaccinating their child
      for HPV. No statistically significant predictors of maternal interest in HPV
      vaccination were found. CONCLUSIONS: Our findings indicate that health service
      planners and providers in Nunavik should be aware of potential barriers to Pap
      smear attendance, especially in the older age groups. Given the low awareness of
      cervical cancer, the Pap smear and the HPV vaccine, education on cervical cancer
      and prevention strategies may be beneficial.

PMID- 22456051
TI  - Level of selected nutrients in meat, liver, tallow and bone marrow from semi
      domesticated reindeer (Rangifer t. tarandus L.).
AB  - OBJECTIVES: To acquire new knowledge on the nutritional composition of semi
      domesticated reindeer (Rangifer t. tarandus L.) and their nutritional value for
      humans. The results could be useful in updating the Norwegian Food Composition
      Database, whose current data on reindeer is limited. STUDY DESIGN: Cross
      sectional study on population of semi-domesticated reindeer from 2 northern
      Norwegian counties (Finnmark and Nordland). METHODS: Semi-domesticated reindeer
      carcasses (n=31) were randomly selected, from which meat, liver, tallow and bone
      marrow samples were collected. Selected vitamins, minerals, fatty acids and total
      lipids were studied. RESULTS: As expected, reindeer meat was found to be lean (2%
      total lipid), thus it is a good source of low-fat meat. The meat was also found
      to be a good source of vitamin B12, docosapentaenoic acid (C22:5 n-3) and alpha
      linolenic acid (C18:3 n-3). Statistically significant differences (p<0.05) in
      most of the nutrient levels between meat and the rest of the studied reindeer
      tissues were observed. In most cases, the liver, tallow and bone marrow had
      higher nutritional values when compared to meat. Liver had the highest
      concentrations of vitamin A, all vitamin B types, vitamin C, iron, selenium and
      the total amount of polyunsaturated fatty acids (n-3). Additionally, liver was
      the only edible tissue that contained vita-mins B9 and C. The vast majority of
      the vitamin concentrations in liver, tallow and bone marrow were significantly
      correlated with the concentrations in meat (p<0.05). CONCLUSIONS: The studied
      tissues from reindeer demonstrated that reindeer is a valuable food source that
      could meet or contribute to the consumers' nutritional recommended daily
      allowance (RDA).

PMID- 22456052
TI  - Sami-speaking municipalities and a control group's access to somatic specialist
      health care (SHC): a retrospective study on general practitioners' referrals.
AB  - OBJECTIVES: The Sami people constitute the indigenous people in northern Norway.
      The objective of this study was to clarify whether they have a similar supply of
      somatic specialist health care (SHC) as others. METHODS: The referrals from
      general practitioners (GPs) in the primary health care (PHC) in the
      administration area of the Sami language law (8 municipalities) were matched with
      a control group of 11 municipalities. Population data was accessed from
      Statistics Norway and the time period 2007-2010 was analysed. The main outcome
      was the number of referrals per 1,000 inhabitants according to age group, gender
      and place of living. RESULTS: 504,292 referrals in northern Norway were
      indentified and the Sami and control group constituted 23,093 and 22,541
      referrals, respectively. The major findings were a similar referral ratio (RR)
      (1.14 and 1.17) (p = 0.624) and women more commonly referred (female/male ratio
      1.45 and 1.41) in both groups. GPs in both groups were loyal to their local
      hospital trust. CONCLUSION: Inhabitants in Sami-speaking municipalities in
      northern Norway have a similar supply of SHC services as controls. Inter
      municipal variation was significant in both groups.

PMID- 22456053
TI  - Vitamin D deficiency among northern Native Peoples: a real or apparent problem?
AB  - Vitamin D deficiency seems to be common among northern Native peoples, notably
      Inuit and Amerindians. It has usually been attributed to: (1) higher latitudes
      that prevent vitamin D synthesis most of the year; (2) darker skin that blocks
      solar UVB; and (3) fewer dietary sources of vitamin D. Although vitamin D levels
      are clearly lower among northern Natives, it is less clear that these lower
      levels indicate a deficiency. The above factors predate European contact, yet pre
      Columbian skeletons show few signs of rickets-the most visible sign of vitamin D
      deficiency. Furthermore, because northern Natives have long inhabited high
      latitudes, natural selection should have progressively reduced their vitamin D
      requirements. There is in fact evidence that the Inuit have compensated for
      decreased production of vitamin D through increased conversion to its most active
      form and through receptors that bind more effectively. Thus, when diagnosing
      vitamin D deficiency in these populations, we should not use norms that were
      originally developed for European-descended populations who produce this vitamin
      more easily and have adapted accordingly.

PMID- 22456055
TI  - Epidemiology of subarachnoid hemorrhage in the Yaeyama Islands, an isolated
      subtropical region of Japan most frequently affected by typhoons: a population
      based study.
AB  - OBJECTIVE: The present study analyzed epidemiological data for patients with
      subarachnoid hemorrhage (SAH) in a subtropical region of Japan that is the most
      frequently affected by typhoons. PATIENTS AND METHODS: The medical records of
      hospitalized patients who had been diagnosed as having SAH at Okinawa Prefectural
      Yaeyama Hospital during a 13-year period were reviewed. Demographic and
      epidemiological data including date and time of onset and activity at onset and
      clinical data were collected. Meteorological data for typhoon's approaches to the
      Yaeyama Islands were obtained from the web-site of the Japan Meteorological
      Agency. In addition, patients who had developed SAH during a period of 3days
      before and after the closest approach of a typhoon (CAT) were examined. RESULTS:
      A total of 94 patients were identified. A monthly peak in August, a weekly peak
      on Monday, and two daily peaks in the evening and morning were observed. The
      incidence of SAH during a period of 3days before and after the CAT was
      approximately twice as high as that on other days, and a statistically
      significant difference was found. CONCLUSION: Periodic patterns of SAH onset
      revealed unusual monthly and circaseptan variations and the usual circadian
      variation. SAH onset was associated with typhoon's approaches.

PMID- 22456056
TI  - Radiation-induced cavernous malformation at the site of arteriovenous
      malformation following gamma knife radiosurgery: case report.

PMID- 22456054
TI  - Stability control of grasping objects with different locations of center of mass
      and rotational inertia.
AB  - The objective of this study was to observe how the digits of the hand adjust to
      varying location of the center of mass (CoM) above or below the grasp and
      rotational inertia (RI) of a handheld object. Such manipulations do not
      immediately affect the equilibrium equations while stability control is affected.
      Participants were instructed to hold a handle, instrumented with 5 force-torque
      transducers and a 3-D rotational tilt sensor, while either the location of the
      CoM or the RI values were adjusted. On the whole, people use 2 mechanisms to
      adjust to the changed stability requirements; they increase the grip force and
      redistribute the total moment between the normal and tangential forces offsetting
      internal torques. The increase in grip force, an internal force, and offsetting
      internal torques allows for increases in joint and hand rotational apparent
      stiffness while not creating external forces-torques that would unbalance the
      equations of equilibrium.

PMID- 22456057
TI  - Injectable reactive biocomposites for bone healing in critical-size rabbit
      calvarial defects.
AB  - Craniofacial injuries can result from trauma, tumor ablation, or infection and
      may require multiple surgical revisions. To address the challenges associated
      with treating craniofacial bone defects, an ideal material should have the
      ability to fit complex defects (i.e. be conformable), provide temporary
      protection to the brain until the bone heals, and enhance tissue regeneration
      with the delivery of biologics. In this study, we evaluated the ability of
      injectable lysine-derived polyurethane (PUR)/allograft biocomposites to promote
      bone healing in critical-size rabbit calvarial defects. The biocomposites
      exhibited favorable injectability, characterized by a low yield stress to
      initiate flow of the material and a high initial viscosity to minimize the
      adverse phenomena of extravasation and filter pressing. After injection, the
      materials cured within 10-12 min to form a tough, elastomeric solid that
      maintained mechanical integrity during the healing process. When injected into a
      critical-size calvarial defect in rabbits, the biocomposites supported ingrowth
      of new bone. The addition of 80 ug mL(-1) recombinant human bone morphogenetic
      protein-2 (rhBMP-2) enhanced new bone formation in the interior of the defect, as
      well as bridging of the defect with new bone. These observations suggest that
      injectable reactive PUR/allograft biocomposites are a promising approach for
      healing calvarial defects by providing both mechanical stability as well as local
      delivery of rhBMP-2.

PMID- 22456058
TI  - Nuclear factor I genes regulate neuronal migration.
AB  - Neuronal migration plays a central role in the formation of the brain, and
      deficits in this process can lead to aberrant brain function and subsequent
      disease. Neuronal migration is a complex process that involves the interaction of
      the neuron with the surrounding environmental milieu, and as such involves both
      cell-intrinsic and cell-extrinsic mechanisms. Studies performed in rodent models
      to investigate the formation of brain structures have provided key insights into
      how neuronal migration is coordinated during development. Within the cerebral
      cortex, glutamatergic neurons derived from the cortical ventricular zone migrate
      radially into the cortical plate, whereas interneurons derived within the
      ventrally located ganglionic eminences migrate tangentially into the cortex.
      Within the embryonic cerebellum, cerebellar granule neuron progenitors migrate
      from the rhombic lip over the surface of the cerebellar anlage, before
      differentiating and migrating radially into the internal granule layer of the
      cerebellum perinatally. In this review, we focus on one family of proteins, the
      nuclear factor I transcription factors, and review our understanding of how these
      molecules contribute to the formation of the hippocampus and the cerebellum via
      the regulation of neuronal migration.

PMID- 22456059
TI  - Modern haemophilia care.
AB  - Haemophilia care has undergone substantial improvements during the past 40-50
      years. Early clotting factor concentrates were not sufficiently refined to enable
      self-administered treatment at home until the 1970s. Unfortunately, these
      advances led to transmission of viral diseases including HIV and hepatitis,
      resulting in an increased burden of morbidity and mortality, especially during
      the 1980s. Throughout the past two decades, product development, including the
      advent of recombinant concentrates, has greatly improved the safety and
      availability of therapy and the focus of care is shifting towards prevention and
      management of disease sequelae. Long-term substitution therapy (prophylaxis) of
      the missing clotting factor is the recommended treatment in severe haemophilia,
      but several research issues remain to be elucidated such as when to start and how
      to optimise these regimens, and when or whether to stop this expensive treatment.
      The major side-effect of treatment, development of inhibitors to the infused
      concentrate, is the main threat to the health of patients and consequently the
      goal of intense research. Development of new products with improved
      pharmacokinetics is the next step to improved therapy.

PMID- 22456060
TI  - Tacrolimus improves the proteinuria remission in patients with refractory IgA
      nephropathy.
AB  - BACKGROUND: Tacrolimus has been reported to be effective in refractory nephrotic
      syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy.
      Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance
      to steroids and/or cytotoxic immunosuppressants based on the supportive therapy
      with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in
      such refractory IgAN patients are extremely ambiguous, and the mechanism of
      tacrolimus improving proteinuria remission needs to be investigated. METHODS: 14
      refractory IgAN patients were enrolled. The patients received tacrolimus (0.05
      0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin
      and calcineurin expression were detected in renal tissues of patients who
      received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte
      injury model was applied to investigate the possible role of tacrolimus in
      proteinuria remission. RESULTS: Of the 14 patients enrolled, 3 were withdrawn
      because serum creatinine increased over 30% baseline. In 11 patients treated with
      tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved
      remission within 1 month. In renal tissues, the expression of calcineurin
      increased while synaptopodin decreased and recovered partially after tacrolimus
      therapy. In an in vitro study, F-actin disrupted in human podocytes after
      stimulation of PAN, while calcineurin increased and synaptopodin decreased. After
      co-treatment with tacrolimus the reorganization of F-actin and the expression of
      calcineurin and synaptopodin recovered. CONCLUSIONS: Tacrolimus showed a rapid
      proteinuria remission in refractory IgAN patients. The possible mechanism of
      tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization
      through inhibition of calcineurin expression.

PMID- 22456061
TI  - Plasticity of surface structures and beta(2)-adrenergic receptor localization in
      failing ventricular cardiomyocytes during recovery from heart failure.
AB  - BACKGROUND: Cardiomyocyte surface morphology and T-tubular structure are
      significantly disrupted in chronic heart failure, with important functional
      sequelae, including redistribution of sarcolemmal beta(2)-adrenergic receptors
      (beta(2)AR) and localized secondary messenger signaling. Plasticity of these
      changes in the reverse remodeled failing ventricle is unknown. We used
      AAV9.SERCA2a gene therapy to rescue failing rat hearts and measured z-groove
      index, T-tubule density, and compartmentalized beta(2)AR-mediated cAMP signals,
      using a combined nanoscale scanning ion conductance microscopy-Forster resonance
      energy transfer technique. METHODS AND RESULTS: Cardiomyocyte surface morphology,
      quantified by z-groove index and T-tubule density, was normalized in reverse
      remodeled hearts after SERCA2a gene therapy. Recovery of sarcolemmal
      microstructure correlated with functional beta(2)AR redistribution back into the
      z-groove and T-tubular network, whereas minimal cAMP responses were initiated
      after local beta(2)AR stimulation of crest membrane, as observed in failing
      cardiomyocytes. Improvement of beta(2)AR localization was associated with
      recovery of betaAR-stimulated contractile responses in rescued cardiomyocytes.
      Retubulation was associated with reduced spatial heterogeneity of electrically
      stimulated calcium transients and recovery of myocardial BIN-1 and TCAP protein
      expression but not junctophilin-2. CONCLUSIONS: In summary, abnormalities of
      sarcolemmal structure in heart failure show plasticity with reappearance of z
      grooves and T-tubules in reverse-remodeled hearts. Recovery of surface topology
      is necessary for normalization of beta(2)AR location and signaling responses.

PMID- 22456062
TI  - Monitoring stimulated cycles during in vitro fertilization treatment with
      ultrasound only--preliminary results.
AB  - OBJECTIVE: To evaluate if monitoring patients by ultrasound (US) only during in
      vitro fertilization (IVF) treatment is safe. DESIGN: Randomized prospective
      study. INTERVENTION: Patients undergoing their first IVF treatment were
      randomized into two groups. The ultrasound only group (study group) was monitored
      by US for follicle size and endometrial thickness without blood tests. In this
      group, only one blood test was taken before human chorionic gonadotropin (hCG)
      injection, to ensure a safe level of estradiol (E(2)) regarding ovarian
      hyperstimulation syndrome (OHSS) risk. The control group was monitored by
      ultrasound plus serum estradiol and progesterone concentration at each visit.
      MAIN OUTCOME MEASURE: Clinical pregnancy rate. RESULTS: No differences were found
      between the groups in the parameters of IVF treatment, induction days, number of
      ampoules, E(2) level of hCG, as well as embryo quality. The clinical pregnancy
      rate was not statistically different between the groups, 57.5% vs. 40.0%,
      respectively (p = 0.25). No OHSS cases were found among the study or control
      groups. CONCLUSION: Ultrasound as a single monitoring tool for IVF cycles is
      reliable, safe, patient friendly, and reduces treatment expenses. In an era of
      cost effectiveness awareness, this regimen should be considered for routine
      management in IVF programs.

PMID- 22456063
TI  - Pencil in the brain: a case of temporal lobe abscess following an intracranial
      penetrating pencil injury.
AB  - The case of a 7-year-old girl with an intracranial penetrating injury due to a
      pencil is presented. The difficulties in diagnosis and the need for a high degree
      of suspicion and for prompt adequate surgical treatment are highlighted.

PMID- 22456064
TI  - Degradation of dichlorvos containing wastewaters using sonochemical reactors.
AB  - The present work deals with application of sonochemical reactors for the
      degradation of dichlorvos containing wastewaters. The sonochemical reactor used
      in the work is a simple ultrasonic horn type operating at 20 kHz with a power
      rating of 270 W. The effect of different operating parameters such as operating
      pH, temperature and power density on the extent of degradation has been
      investigated initially followed by intensification studies using additives such
      as hydrogen peroxide, Fenton's reagent and CCl(4). It has been observed that low
      frequency sonochemical reactors can be effectively used for treatment of
      pesticide wastewaters and acidic conditions and optimum values of temperature and
      power dissipation favors the degradation of dichlorvos. The efficacy of
      sonochemical reactors can be further enhanced by using different additives at
      optimized loadings. Complete removal of the pesticide at the given loading has
      been obtained using an optimized combination of ultrasound and Fenton's
      chemistry. The controlling mechanism for the sonochemical degradation has been
      confirmed to be the free radical attack based on the studies involving radical
      scavengers. The novelty of the present work is clearly established as there have
      been no earlier studies dealing with degradation of dichlorvos pesticide using
      sonochemical reactors operating at low frequency which offers distinct advantage
      in terms of cost and the stability of the reactor.

PMID- 22456066
TI  - [Challenges and upcoming revolution in autoimmune diseases in children].

PMID- 22456067
TI  - [Prevalence of food allergy in children under 2 years of age in three cities in
      China].
AB  - OBJECTIVE: To estimate the prevalence and clinical features of food allergy in
      children aged 0 - 2 years. METHOD: From January to February, 2009 and January to
      May, 2010, all well-infants and young children between the age of 0 and 2 years
      attending routine health visits at the Department of Primary Child Care, in
      Chongqing, Zhuhai and Hangzhou were invited to participate in the study. Parents
      completed questionnaires and all children were skin prick tested (SPT) to a panel
      of 10 foods (egg white, egg yolk, cow's milk, soybean, peanut, wheat, fish,
      shrimp, orange and carrot). Based on the results of SPT and medical history, the
      subjects under went the suspected food elimination and oral food challenge under
      medical supervision. Food allergy was confirmed by the food challenge test.
      RESULT: Totally 1687 children were recruited by the consent of their parents. Of
      1687 children approached, 1604 (550 of Chongqing, 573 of Zhuhai and 481 of
      Hangzhou) fulfilled the study criteria for diagnosing food allergy. One hundred
      children were confirmed to have challenge-proven food allergy in 3 cities (40 of
      Chongqing, 33 of Zhuhai and 27 of Hangzhou). The prevalence of food allergy in 0
      2 years old children in Chongqing was 7.3%, in Zhuhai was 5.8% and in Hangzhou
      was 5.5%. There was no significant difference in the prevalence of food allergy
      in children under 2 years among the three cities, and the average prevalence for
      food allergy in children under 2 years was 6.2%. Egg (3.0% - 4.4%) was the most
      common allergen, followed by cow's milk (0.83% - 3.5%), shrimp (0.17% - 0.42%)
      and fish (0.17% - 0.21%). CONCLUSION: The prevalence of food allergy in 0 - 2
      years old children in China was 5.5% - 7.3%. There was no significant difference
      in the prevalence of food allergy in children under 2 years of age among the
      three cities. Egg was the most common allergen, followed by cow's milk, shrimp
      and fish.

PMID- 22456068
TI  - [Clinical features, mutation of the GNAS1 and pathogenesis of progressive osseous
      heteroplasia].
AB  - OBJECTIVE: To investigate the clinical features, mutation of the GNAS1 and
      pathogenesis of progressive osseous heteroplasia (POH). METHOD: The typical
      clinical, pathological and radiographic features of a boy with POH were collected
      and summarized following family survey. The GNAS1 gene sequence of all family
      members were amplified by polymerase chain reaction (PCR) and the products were
      sequenced directly to identify the mutations. A literature review and long-term
      follow up were also conducted. RESULT: The patient was an 11-year-old boy who had
      the onset in infancy, which indicates a chronic progressive cause of disease. The
      clinical features include the unsmooth local skin of the right shank where spread
      many rigid rice-like or irregular slabby uplifts, slabby bone-like sclerosis on
      the left lower mandible, left masticatory muscles, in lateral subcutaneous site
      of left hip joint and deep tissue, accompanied by gradually progressive
      difficulty in opening mouth. Histopathology showed that there were loosened
      hyperplasia of fibroblast and interstitial edema with punctiformed ossification.
      Radiographs showed flocculence hyperdense image in the subcutaneous tissues and
      muscles around left lower mandible, and the left masticatory muscles were
      obviously involved. The 3-dimensional computed tomography showed dislocations of
      the left temporomandibular joint. Sheeted hyperdense image with inequable density
      could be noted in lateral muscles of the left hip. And lamellar hyperdense image
      parallel to the long axis of the bone could be seen in the subcutaneous dorsum of
      the left foot and achilles tendon. Macro-thumb and of brachydactylia of the hands
      and feet were not present. The level of calcium, phosphorus and alkaline
      phosphatase in the blood were normal. Brother of same father but different
      mothers was free of the disease and no patient of the same disease was found in
      maternal line and paternal lines. A mutated allele in exon 7 and a polymorphism
      in exon 5 were found in GNAS1 gene in both of the patient and his father.
      CONCLUSION: There is possibility/likelihood/probability that Chinese children
      could develop POH. Translocated dermal ossification began in infancy and shows a
      progressive cause in childhood. The disease is characterized by the heterotopic
      ossification of the skin, deep tissue, muscles and facial surface tissues. The
      location of the mutation in this study was different from that reported in abroad
      studies although exist in the same exons.

PMID- 22456065
TI  - Persistence of hyperdense middle cerebral artery sign on follow-up CT scan after
      intravenous thrombolysis is associated with poor outcome.
AB  - BACKGROUND: The rates and extent of recovery in acute ischemic stroke (AIS)
      patients treated with intravenous tissue plasminogen activator (IV-tPA) remain
      highly variable. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment
      unenhanced computerized tomography (CT) of the brain represents the presence of
      thrombus, often associated with severe neurological deficits and poor clinical
      outcome at 3 months. However, HMCAS is reliable only in AIS patients managed
      conservatively. In patients treated with systemic thrombolysis, HMCAS may
      disappear (representing clot dissolution) or persist (persisting clot) on the
      follow-up CT scan of the brain. We aimed at evaluating whether disappearance or
      the persistence of HMCAS on follow-up CT scan of the brain can predict the final
      outcome at 3 months. METHODS: Data from consecutive AIS patients treated with IV
      tPA, in a standardized protocol, from January 2007 to March 2010 were included in
      the prospective thrombolysis registry at our tertiary care center. For this
      evaluation, posterior circulation stroke was excluded. HMCAS was assessed on
      admission as well as follow-up CT by 2 independent stroke neurologists, blinded
      to the patient data or outcomes. Functional outcomes assessed by the modified
      Rankin Scale (mRS) at 3 months were dichotomized as good (mRS score 0-1) and poor
      (mRS score 2-6). The data were analyzed for the early predictors of poor
      functional outcome with SPSS version 19 for Windows. RESULTS: Of the total of
      2,238 patients admitted during the study period, 226 (11%) with anterior
      circulation AIS treated with intravenous thrombolysis were included. Median age
      of the patients was 65 years (range 19-92), 63% were males and they had a median
      National Institutes of Health Stroke Scale (NIHSS) score of 16 points (range 4
      32). HMCAS was observed on admission CT scan in 109 (48.2%) patients and
      persisted on follow-up CT in 52 (47.7%) of them. Overall, 108 (47.8%) patients
      achieved poor functional outcome at 3 months. Admission NIHSS score (OR per 1
      point increase = 1.241; 95% CI = 1.151-1.337, p < 0.0005), lesser change in NIHSS
      score at 24 h (OR per 1-point reduction = 0.730; 95% CI = 0.666-0.800, p <
      0.0005) and persistence of HMCAS on follow-up CT scan (OR = 3.352; 95% CI = 1.991
      11.333, p = 0.039) were associated with poor outcome at 3 months. CONCLUSION:
      Persistence of HMCAS on the follow-up CT scan of the brain in acute ischemic
      stroke patients treated with IV-tPA can be used as an early predictor of poor
      functional outcome.

PMID- 22456069
TI  - [Analysis of prenatal diagnosis for seven high-risk fetuses with Wiskott-Aldrich
      syndrome].
AB  - OBJECTIVE: To investigate the value of gene analysis of amniotic fluid exfoliated
      cells and WASP detection from cord blood in prenatal diagnosis of high-risk fetus
      with Wiskott-Aldrich syndrome. METHOD: Seven patients with Wiskott-Aldrich
      syndrome were diagnosed by gene analysis and WASP detected by flow cytometry from
      2008 to 2010. After detailed inquiry for medical history and gene analysis of
      related family members, seven pedigree trees were drawn, including 15 carriers of
      abnormal genes. From 2008 to 2011, seven samples of amniotic cell gotten by
      amniocentesis were collected from seven high-risk pregnant women with abnormal
      gene during 18 to 20 gestational weeks. WASP gene was amplified by polymerase
      chain reaction (PCR) from DNA of amniotic cell gotten and sequencing was
      performed directly on the PCR products forward and reversely. Embryo blood sample
      was collected from one high-risk fetus by needle puncture of umbilical blood
      vessel and WASP expression was detected by flow cytometry. Karyotyping was
      performed in amniotic cell gotten cultivated by orthotopic slice and G band
      staining. Gene analysis of WASP, WASP expression detected by flow cytometry and
      evaluation of immune function were reexamined in high-risk fetus after delivery.
      RESULT: Amniocentesis and culture of amniotic cell succeeded in all the seven
      fetuses. Gene analysis and karyotyping showed that one male fetus and four female
      fetuses were normal and two female fetuses were carriers. WASP expression
      detected from embryo blood sample of the patient was normal. After delivery, the
      result of gene analysis, WASP detection and evaluation of immune function was the
      same as that of prenatal diagnosis. CONCLUSION: Karyotyping, gene analysis and
      WASP detection of cord blood can provide reliable service of prenatal diagnosis
      for high-risk pregnant women with Wiskott-Aldrich syndrome.

PMID- 22456070
TI  - [SGI-PS-CMA evidence-based recommendations for the diagnosis and management of
      juvenile idiopathic arthritis (oligoarticular and polyarticular)].

PMID- 22456071
TI  - [Interpretation of the evidence-based recommendations for the diagnosis and
      management of juvenile idiopathic arthritis (oligoarticular and polyarticular)].

PMID- 22456072
TI  - [Joints assessment for juvenile arthritis].

PMID- 22456073
TI  - [Changing in pathological classification of IgA nephropathy].

PMID- 22456074
TI  - [Molecular characteristics of methicillin resistant Staphylococcus aureus
      isolated from Chinese children].
AB  - OBJECTIVE: To investigate the molecular characteristics of methicillin-resistant
      Staphylococcus aureus (MRSA) isolates from Chinese children in seven cities.
      METHOD: A total of 134 MRSA isolates were collected from nine hospitals.
      Multilocus sequence typing and spa typing were analyzed by polymerase chain
      reaction (PCR), and staphylococcal chromosomal cassette mec (SCCmec) type was
      analyzed by multiplex PCR. The Panton-Valentine leukocidin (pvl) gene was also
      detected. RESULT: Most MRSA strains were isolated from pneumonia and skin and
      soft tissue infection (SSTIs) patients, accounting for 82.1%. Overall, 16
      sequence types (STs) were obtained, and CC59 (51.7%) was found to be the most
      prevalent, which included ST 59 and ST 338, followed by ST239 (16.4%). SCCmec
      types II, III, IV, and V were also identified in the current study. SCCmec type
      IV was the most predominant type at 50.0%, followed by SCCmec type V at 23.9% and
      III at 23.9%. SCCmec subtypes IVa, IVc, and IVg were found among SCCmec type IV
      strains, whereas IVa was the main subtype at 77.6%. Twenty-six spa types were
      also identified, among which the predominant type was t437 (47.8%). The
      prevalence of pvl genes and the SCCmec type of strain was relevant, and the pvl
      gene positive rate was higher in SCCmec type IV and V-type strains than in SCCmec
      type II and III strains (58.6% vs. 14.3%, P < 0.05); there was a significant
      difference between them. In the strains isolated from pneumonia and SSTIs, ST59
      MRSA-IVa(t437) was the predominant clone. There were five clones detected from
      the strains isolated from septicemia, with ST59-MRSA-IVa(t437) and ST59-MRSA
      V(t437) as the main clones (57.1%). Various predominant clones existed in
      different regions. ST59-MRSA-IVa(t437) was the prevalent clone in the Guangzhou,
      Beijing, Chongqing, and Shenzhen areas, whereas ST239-MRSA-III(t037) was the
      prevalent clone in the Shanghai area. Fifty percent of the isolates from the
      Wenzhou area belonged to ST910-MRSA-V(t318), whereas three clinical strains
      isolated from the Shenyang region belonged to three different types. CONCLUSION:
      The results indicate that MRSA isolates from Chinese children are largely
      associated with the ST59-MRSA-IV(t437) and ST239-MRSA-III(t037) clones. These two
      may belong to community-acquired MRSA and hospital-acquired ones, respectively.
      Different prevalent clones were detected in different diseases and different
      regions. Therefore, there is a need to conduct further research on clinical
      isolates, which can guide the choice of antibiotic treatment and the examination
      of MRSA prevalence.

PMID- 22456075
TI  - [Effect of bronchoscopic cryosurgery in twenty-two children with lower airway
      stenosis].
AB  - OBJECTIVE: To analyze the effect and safety of bronchoscopic cryosurgery in
      children with lower airway stenosis caused by granulation and fiber hyperplasia.
      METHOD: Twenty-two patients had undergone bronchoscopic examination and
      cryosurgery, 18 patients with atelectasis caused by Mycoplasma pneumoniae
      pneumonia, 2 patients with endobronchial tuberculosis (EBTB), 1 patient with
      atelectasis caused by granulation tissue after bronchial foreign body, and 1 case
      who had severe dyspnea, with tracheal stenosis after long-term endotracheal
      intubation during surgery for heart disease. All the patients under went
      bronchoscopic cryosurgery for several times, 1 case with severe tracheal stenosis
      was operated by electric coagulation before cryosurgery. Before and after the
      treatment, all the patients were evaluated based on clinical symptoms, tracheal
      lumen by bronchoscopy, chest CT for atelectasis and pulmonary function for
      tracheal stenosis. RESULT: The patients were treated with cryosurgery for 1-4
      times. Sixteen cases were markedly improved, clinical symptoms disappeared
      completely, no granulation and fiber hyperplasia were found during bronchoscopy,
      and all the atelectasis were cured. After the treatment, the bronchial lumen
      diameter of the patient with tracheal stenosis was increased from 2 mm to about 5
      mm, the tidal volume increased from 3.0 ml/kg to 8.8 ml/kg. Five cases were
      effectively improved, the clinical symptoms also disappeared, during bronchoscopy
      and bronchial alveolar lavage (BAL), no granulation and fiber hyperplasia were
      found, but some distal bronchial tubes were atresia or narrowed, the lumen was
      patent, the atelectasis recovered partially. In 1 case the treatment was
      ineffective, as the clinical symptoms and granulation disappeared, but because
      almost all distal bronchi were atresia or narrow, the lumen was not patent during
      BAL, there was no change on chest CT. The total effective rate was 21/22 (95.5%).
      No severe complications occurred during and after the procedures. All the patient
      were followed up for 1 - 12 months, no case had recurrence. CONCLUSION: Treatment
      with bronchoscopic cryosurgery is a safe and effective methods to tracheal
      stenosis caused by granulation tissue and fiber hyperplasia in children.

PMID- 22456076
TI  - [Clinical and genetic analysis of a family with leukoencephalopathy with brain
      stem and spinal cord involvement and lactate elevation].
AB  - OBJECTIVE: Leukoencephalopathy with brain stem and spinal cord involvement and
      lactate elevation (LBSL) is a rare autosomal recessive disease. Affected
      individuals are invariably compound heterozygous for two mutations in DARS2. No
      reports of LBSL patients have been published in the mainland of China. The aim of
      this study was to explore the clinical and genetic features of a family with
      LBSL, which may contribute to definite diagnosis, genetic counseling and prenatal
      diagnosis of this rare disease in China. METHODS: Clinical data of the proband
      and other family members as well as DNA samples were collected. Clinical features
      including symptoms, signs and cranial MRI were analyzed. All 17 exons and exon
      intron boundaries of DARS2 gene were amplified with polymerase chain reaction
      (PCR) and directly sequenced for genomic DNA. The mutation was proved by DNA
      restriction enzyme digestion of PCR-amplified fragments. RESULTS: (1) The
      clinical features of patient with LBSL included slowly progressive cerebellar
      ataxia and spasticity, the neurologic dysfunction involving the legs more than
      the arms, and with characteristic abnormalities observed on brain and spinal cord
      MRI. (2) Two mutations were identified, one was a novel missense mutation [c.665
      G > A(p.Gly222Asp)] in DARS2 gene exon 8, the other (c.228-16 C > G) was in DARS2
      gene intron 3. CONCLUSION: This is the first report on LBSL patient and DARS2
      mutation in China. p.Gly222Asp mutation is a novel mutation not reported around
      the world yet.

PMID- 22456077
TI  - [Relationship between waist circumference development curve of children and
      hypertension and risk of hypertension].
AB  - OBJECTIVE: The 85th percentile of waist circumference (WC) is considered an
      appropriate cutoff for Chinese children in the prediction of cardiovascular risks
      in previous researches, but the risk for hypertension of moderate WC maybe
      underestimated. The purpose of this study was to understand the characteristics
      of the WC curve trajectory of children with hypertension and to determine the
      appropriate cutoffs for waist circumference for Chinese school-age children and
      adolescents for predicting hypertension risk factors. METHODS: A total of 8194
      Han children aged 7 - 17 years were selected from schools in Suzhou, Hefei, and
      Chizhou cities in Anhui province by stratified cluster sampling. WC and blood
      pressure were accurately measured in all subjects. LMS (lambda-mu-sigma) method
      was used to construct WC centile curves. Optimal WC cutoffs were determined by
      comparing the performance of different percentile sets of WC cutoffs in
      predicting hypertension risk factors. RESULTS: The fitted LMS curves of WC for
      the group of boys with hypertension deviate in parallel from that for the
      corresponding curve in the entire boy study population with higher WC. The WC
      curves for the group of girls with hypertension gradually upward deviated from
      the corresponding curve before 12 years of age and then gradually returned to the
      corresponding curve. WC of boys at the percentiles of 60 was already associated
      with an increased risk of hypertension and hazard ratio of WC at percentiles of
      60, 70, 80, and 90 increased from 1.88(95%CI: 1.18 - 2.99) to 4.87 (95%CI: 3.31 -
      7.16). WC of girls at the percentiles of 70 was already associated with an
      increased risk of hypertension and hazard ratio of WC at percentiles of 70, 80,
      and 90 increased from 1.71 (95%CI: 1.07 - 2.73) to 3.32 (95%CI: 2.16 - 5.09).
      CONCLUSIONS: The WC growth trajectory of children with hypertension varies with
      gender. WC is an independent predictor of childhood hypertension, even when it is
      well within what is now defined as the normal range of WC. Thus, it is helpful to
      prevent the risk of cardiovascular disease of children using the parameter that
      WC cut-off level lower than 85th percentile.

PMID- 22456078
TI  - [Diagnosis and treatment of leukocyte adhesion deficiency].

PMID- 22456079
TI  - [Progresses in laboratory diagnosis of common pediatric viral infections].

PMID- 22456080
TI  - [Dose option of haemophilia prophylaxis in children].

PMID- 22456081
TI  - [Recent advances in leukemia stem cell research].

PMID- 22456082
TI  - [Summary of National Conference on Pediatric Rheumatology in 2011].

PMID- 22456083
TI  - Injectable calcium-phosphate-based composites for skeletal bone treatments.
AB  - Alpha-tricalcium-phosphate-based bone cements hydrolyze and set, producing
      calcium-deficient hydroxyapatite. They can result in an effective solution for
      bone defect reconstruction due to their biocompatibility, bioactivity and
      adaptation to shape and bone defect sizes, together with an excellent contact
      between bone and graft. Moreover, the integration of hydrogel phase based on
      poly(vinyl alcohol) (PVA) to H-cem-composed of alpha-tricalcium phosphate (98%
      wt) and hydroxyapatite (2% wt)-allows improving the mechanical and biological
      properties of the cement. The aim of this work was to evaluate the influence of
      the PVA on relevant properties for the final use of the injectable bone
      substitute, such as setting, hardening, injectability and in vivo behaviour. It
      was shown that by using PVA it is possible to modulate the setting and hardening
      properties: large increase in injectability time (1 h) in relation with the plain
      cement (few minutes) was achieved. Moreover, in vivo tests confirmed the ability
      of the composite to enhance bone healing in trabecular tissue. Histological
      results from critical size defects produced in rabbit distal femoral condyles
      showed after 12 weeks implantation a greater deposition of new tissue on bone
      composite interfaces in comparison to bone-cement interfaces. The quality of bone
      growth was confirmed through histomorphometric and microhardness analysis. Bone
      formation in the composite implantation sites was significantly higher than in H
      cem implants at both times of evaluation.

PMID- 22456084
TI  - The performance of decellularized adipose tissue microcarriers as an inductive
      substrate for human adipose-derived stem cells.
AB  - With the aim of developing a clinically-translatable cell expansion and delivery
      vehicle for adipose tissue engineering, the adipogenic differentiation of human
      adipose-derived stem cells (ASCs) was investigated on microcarriers fabricated
      from human decellularized adipose tissue (DAT). ASCs seeded on the DAT
      microcarriers and cultured in adipogenic differentiation medium within a low
      shear spinner culture system demonstrated high levels of adipogenic
      differentiation, as measured by the expression of adipogenic genes, glycerol-3
      phosphate dehydrogenase (GPDH) enzyme activity, and intracellular lipid
      accumulation. In contrast, gelatin microcarrier controls did not demonstrate
      significant adipogenesis, emphasizing the role of the native matrix in mediating
      ASC differentiation. Interestingly, ASCs cultured on the DAT microcarriers in
      proliferation medium expressed elevated levels of the adipogenic markers,
      suggesting that the DAT provided an adipo-inductive substrate for the human ASCs.
      In vivo testing of the DAT and gelatin microcarriers in a subcutaneous Wistar rat
      model confirmed injectability and demonstrated stable volume retention over 28
      days. Under histological analysis, the DAT microcarriers demonstrated no evidence
      of immunogenicity or cytotoxicity, with the DAT supporting cellular infiltration
      and tissue remodeling. Pre-seeding the DAT microcarriers with allogenic rat ASCs
      enhanced cellularity and angiogenesis within the implant region.

PMID- 22456085
TI  - The migration of olfactory ensheathing cells during development and regeneration.
AB  - The primary olfactory nervous system is unique in that it continuously renews
      itself and regenerates after injury. These properties are attributed to the
      presence of olfactory glia, termed olfactory ensheathing cells (OECs). Evidence
      is now emerging that individual OEC populations exist with distinct anatomical
      localisations and physiological properties, but their differential roles have not
      been determined. Unlike other glia, OECs can migrate from the periphery into the
      central nervous system, and organised OEC migration can enhance axonal extension
      after injury. Despite this, the mechanisms regulating OEC migration are largely
      unknown. Here, we provide an overview of the roles of OECs in development and
      adulthood. We review the latest research describing the differences between
      individual OEC subpopulations and discuss potential regulatory mechanisms for OEC
      guidance and migration. Using advanced time lapse techniques, we have obtained
      novel insights into how OECs behave in a complex multicellular environment which
      we discuss here with particular focus on cell-cell interactions. Significantly,
      transplantation of OECs constitutes a promising novel therapy for nerve injuries,
      but results are highly variable and the method needs improvement. We here review
      the roles of transplanted OECs in neural repair of damaged neuronal tracts
      distinct from the primary olfactory nervous system.

PMID- 22456086
TI  - Landfill leachate treatment using sub-surface flow constructed wetland by Cyperus
      haspan.
AB  - Performance evaluation of pilot scale sub-surface constructed wetlands was
      carried out in treating leachate from Pulau Burung Sanitary Landfill (PBSL). The
      constructed wetland was planted with Cyperus haspan with sand and gravel used as
      substrate media. The experiment was operated for three weeks retention time and
      during the experimentation, the influent and effluent samples were tested for its
      pH, turbidity, color, total suspended solid (TSS), chemical oxygen demand (COD),
      biochemical oxygen demand (BOD(5)), ammonia nitrogen (NH(3)-N), Total phosphorus
      (TP), total nitrogen (TN) and also for heavy metals such as iron (Fe), magnesium
      (Mg), manganese (Mn) and zinc (Zn) concentrations. The results showed that the
      constructed wetlands with C. haspan were capable of removing 7.2-12.4% of pH,
      39.3-86.6% of turbidity, 63.5-86.6% of color, 59.7-98.8% of TSS, 39.2-91.8% of
      COD, 60.8-78.7% of BOD(5), 29.8-53.8% of NH(3)-N, 59.8-99.7% of TP, 33.8-67.0% of
      TN, 34.9-59.0% of Fe, 29.0-75.0% of Mg, 51.2-70.5% of Mn, and 75.9-89.4% of Zn.
      The significance of removal was manifested in the quality of the effluent
      obtained at the end of the study. High removal efficiencies in the study proved
      that leachate could be treated effectively using subsurface constructed wetlands
      with C. haspan plant.

PMID- 22456087
TI  - MspA1 polymorphism of the CYP17 gene in breast cysts.
AB  - OBJECTIVE: To study the prevalence of breast cysts in several age groups of the
      general female population and their association with the MspAI polymorphism of
      the gene CYP17. RESULTS: In 204 ultrasound tests, cysts were present in 22% of
      the studied population. The epidemiological-clinical profile of these women was
      Caucasian, aged 41-50 years, regular menstrual cycles, multiparous and
      complaining of mastalgia. The genetic distribution of polymorphisms of the gene
      displayed Hardy-Weinberg equilibrium and the wild homozygous phenotype was
      observed in 36.4% of the case group and in 37.6% of the control groups; the
      heterozygous phenotype was observed in 50% of the study group and 46.3% of
      control group and a mutated homozygous phenotype was seen in 13.6% of the study
      group and 16.1% of the controls. There was no statistically significant
      difference between the groups (p = 0.92). CONCLUSION: The prevalence and most of
      the epidemiological profile of breast cysts were in agreement with the
      literature. There was no statistically significant difference among the genotypic
      groups (wild homozygous, heterozygous and mutated homozygous), despite a slightly
      increased frequency of the mutated genotype in the control group. This difference
      indicates a trend of the MspAI polymorphism of the gene CYP17 to act as a
      protective factor against the development of breast cysts.

PMID- 22456088
TI  - Integrating usability testing and think-aloud protocol analysis with "near-live"
      clinical simulations in evaluating clinical decision support.
AB  - PURPOSE: Usability evaluations can improve the usability and workflow integration
      of clinical decision support (CDS). Traditional usability testing using scripted
      scenarios with think-aloud protocol analysis provide a useful but incomplete
      assessment of how new CDS tools interact with users and clinical workflow. "Near
      live" clinical simulations are a newer usability evaluation tool that more
      closely mimics clinical workflow and that allows for a complementary evaluation
      of CDS usability as well as impact on workflow. METHODS: This study employed two
      phases of testing a new CDS tool that embedded clinical prediction rules (an
      evidence-based medicine tool) into primary care workflow within a commercial
      electronic health record. Phase I applied usability testing involving "think
      aloud" protocol analysis of 8 primary care providers encountering several
      scripted clinical scenarios. Phase II used "near-live" clinical simulations of 8
      providers interacting with video clips of standardized trained patient actors
      enacting the clinical scenario. In both phases, all sessions were audiotaped and
      had screen-capture software activated for onscreen recordings. Transcripts were
      coded using qualitative analysis methods. RESULTS: In Phase I, the impact of the
      CDS on navigation and workflow were associated with the largest volume of
      negative comments (accounting for over 90% of user raised issues) while the
      overall usability and the content of the CDS were associated with the most
      positive comments. However, usability had a positive-to-negative comment ratio of
      only 0.93 reflecting mixed perceptions about the usability of the CDS. In Phase
      II, the duration of encounters with simulated patients was approximately 12 min
      with 71% of the clinical prediction rules being activated after half of the visit
      had already elapsed. Upon activation, providers accepted the CDS tool pathway 82%
      of times offered and completed all of its elements in 53% of all simulation
      cases. Only 12.2% of encounter time was spent using the CDS tool. Two predominant
      clinical workflows, accounting for 75% of all cases simulations, were identified
      that characterized the sequence of provider interactions with the CDS. These
      workflows demonstrated a significant variation in temporal sequence of potential
      activation of the CDS. CONCLUSIONS: This study successfully combined "think
      aloud" protocol analysis with "near-live" clinical simulations in a usability
      evaluation of a new primary care CDS tool. Each phase of the study provided
      complementary observations on problems with the new onscreen tool and was used to
      refine both its usability and workflow integration. Synergistic use of "think
      aloud" protocol analysis and "near-live" clinical simulations provide a robust
      assessment of how CDS tools would interact in live clinical environments and
      allows for enhanced early redesign to augment clinician utilization. The findings
      suggest the importance of using complementary testing methods before releasing
      CDS for live use.

PMID- 22456089
TI  - The influence of the blood handling process on the measurement of circulating TGF
      beta1.
AB  - In order to evaluate the impact of blood sample handling processes on circulating
      TGF-beta1 levels, blood specimens were obtained from 13 healthy volunteers using
      different handling processes (kept at room temperature (RT) or on ice before
      centrifugation, using different centrifugal forces). TGF-beta1 levels were
      measured using an enzyme-linked immunosorbent assay. A paired-T test was used for
      statistical analysis. The TGF-beta1 level in on-ice serum was significantly lower
      than that in room-temperature serum (P<0.001), and both were significantly higher
      than that found in on-ice plasma (P<0.001). Compared with on-ice plasma samples,
      the longer the samples were kept at RT, the higher the levels of TGF-beta1 in
      plasma (P=0.268, 0.040, and 0.0015 for 5 min, 30 min, and 60 min in RT,
      respectively). Compared with plasma centrifuged at 2,500*g for 30 min, the TGF
      beta1 levels were much lower than those found in plasma centrifuged at 1,200*g
      for 10 min (P=0.003); and a double centrifugation before TGF-beta1 detection,
      significantly decreased the level (P<0.001). It is suggested that the optimal
      sampling conditions for the detection of TGF-beta1 should be plasma prepared on
      ice and spun down at a higher centrifugal force.

PMID- 22456090
TI  - Development of an outpatient native kidney biopsy service in low-risk patients: a
      multidisciplinary approach.
AB  - BACKGROUND: In the US, native kidney biopsies are usually inpatient procedures.
      We developed an outpatient biopsy protocol for low-risk patients and assessed its
      safety and efficacy. METHODS: Patients with an SBP <140 mm Hg and a BMI <=35 who
      were not taking anticoagulants, ASA and NSAIDS in the preceding week were
      included. Biopsies were performed under ultrasound guidance using a 15-gauge
      needle that changed to a 14-gauge needle during the study. Patients were
      discharged after 5 h of observation if there were no signs of bleeding.
      Complications were carefully recorded. RESULTS: Between November 2008 and April
      2011, 105 patients underwent outpatient renal biopsies. A 15-gauge needle was
      used in 43 patients (group A) while a 14-gauge needle was used in 62 (group B). A
      median of 25 (range 4-64) glomeruli were obtained in group A versus 39 (range 0
      107) in group B (p < 0.001). Complications requiring admission for observation
      occurred in 7 patients (16%) in group A versus 5 patients (8%) in group B (p =
      0.22). One patient in group B had bleeding requiring intervention, while all
      other complications were minor. Nine complications occurred during the
      observation period, while 3 patients presented >48 h after biopsy. The mean cost
      per patient for each outpatient biopsy was USD 976 versus USD 5,489 for
      inpatients. CONCLUSIONS: In a selected low-risk population, outpatient renal
      biopsy is safe with low complication rates and results in significant cost
      savings relative to elective inpatient biopsies. The use of a 14-gauge biopsy
      needle resulted in a greater yield of glomeruli without increased complications.

PMID- 22456091
TI  - Symptomatic apoplexy in intramedullary ependymoma: a report of a pediatric
      patient.
AB  - Spinal intramedullary ependymomas often harbor clinically asymptomatic
      intratumoral bleeds. Such tumors presenting with apoplectic events have not been
      described in the literature. The authors report on a 2-year-old female who
      presented with sudden loss of sensorimotor functions below the thoracic spine as
      a consequence of hemorrhage within an intramedullary ependymoma. The clinical,
      radiological, and surgical findings are described. Gross total resection provided
      near-normal spinal functions in the present case.

PMID- 22456092
TI  - Polycystin-1 and polycystin-2 are both required to amplify inositol-trisphosphate
      induced Ca2+ release.
AB  - Autosomal dominant polycystic kidney disease is caused by loss-of-function
      mutations in the PKD1 or PKD2 genes encoding respectively polycystin-1 and
      polycystin-2. Polycystin-2 stimulates the inositol trisphosphate (IP(3)) receptor
      (IP(3)R), a Ca(2+)-release channel in the endoplasmic reticulum (ER). The effect
      of ER-located polycystin-1 is less clear. Polycystin-1 has been reported both to
      stimulate and to inhibit the IP(3)R. We now studied the effect of polycystin-1
      and of polycystin-2 on the IP(3)R activity under conditions where the cytosolic
      Ca(2+) concentration was kept constant and the reuptake of released Ca(2+) was
      prevented. We also studied the interdependence of the interaction of polycystin-1
      and polycystin-2 with the IP(3)R. The experiments were done in conditionally
      immortalized human proximal-tubule epithelial cells in which one or both
      polycystins were knocked down using lentiviral vectors containing miRNA-based
      short hairpins. The Ca(2+) release was induced in plasma membrane-permeabilized
      cells by various IP(3) concentrations at a fixed Ca(2+) concentration under
      unidirectional (45)Ca(2+)-efflux conditions. We now report that knock down of
      polycystin-1 or of polycystin-2 inhibited the IP(3)-induced Ca(2+) release. The
      simultaneous presence of the two polycystins was required to fully amplify the
      IP(3)-induced Ca(2+) release, since the presence of polycystin-1 alone or of
      polycystin-2 alone did not result in an increased Ca(2+) release. These novel
      findings indicate that ER-located polycystin-1 and polycystin-2 operate as a
      functional complex. They are compatible with the view that loss-of-function
      mutations in PKD1 and in PKD2 both cause autosomal dominant polycystic kidney
      disease.

PMID- 22456093
TI  - Handgrip strength predicts pressure ulcers in patients with hip fractures.
AB  - OBJECTIVE: Pressure ulcer (PU) is a frequent complication of hip fracture.
      Studies were carried out to identify the risk factors of PU development after hip
      fractures. The objective of the study was to determine the role of anthropometric
      measurements and handgrip strength as predictors of PUs in patients with hip
      fractures during their hospital stay and 30 d after discharge, which has not yet
      been established. METHODS: Ninety-two consecutive patients with hip fractures who
      were older than 65 y old and admitted to an orthopedic unit were prospectively
      evaluated. Within the first 72 h of admission, each patient's characteristics
      were recorded, anthropometric measurements were taken (circumferences of the arm,
      waist, thigh, calf, triceps, and biceps and subscapular and suprailiac
      skinfolds), handgrip strength was measured, and blood samples were collected. PU
      evaluations were performed during the hospital stay and 30 d after hospital
      discharge. RESULTS: Three patients were excluded because of PUs before
      hospitalization. Eighty-nine patients (average age 80.6 +/- 7.5 y) were studied;
      70.8% were women, and 49.4% developed PUs during their hospital stay. In a
      univariate analysis, length of hospital stay (P = 0.001) and handgrip strength (P
      = 0.02), but not body circumferences and skinfolds, were associated with PUs
      during a hospital stay. Only handgrip strength (P = 0.007) was associated with
      PUs 30 d after hospital discharge. In a multivariate analysis, only handgrip
      strength was found to predict PU development at these points. CONCLUSION:
      Handgrip strength was found to predict PU development in patients with hip
      fractures during their hospital stay and 30 d after discharge.

PMID- 22456094
TI  - Does antidepressant treatment improve cognition in older people with
      schizophrenia or schizoaffective disorder and comorbid subsyndromal depression?
AB  - BACKGROUND: Subsyndromal symptoms of depression (SSD) in patients with
      schizophrenia are common and clinically important. While treatment of depression
      in major depressive disorder may partially ameliorate cognitive deficits, the
      cognitive effects of antidepressant medications in patients with schizophrenia or
      schizoaffective disorder and SSD are unknown. METHODS: The goal of this study was
      to assess the impact of SSD and their treatment on cognition in participants with
      schizophrenia or schizoaffective disorder aged >=40 years. Participants were
      randomly assigned to a flexible dose treatment with citalopram or placebo
      augmentation of their current medication for 12 weeks. An ANCOVA compared
      improvement in the cognitive composite scores, and a linear model determined the
      moderation of cognition on treatment effects based on the Hamilton Depression
      Rating Scale and the Calgary Depression Rating Scale scores between treatment
      groups. RESULTS: There were no differences between the citalopram and placebo
      groups in changes in cognition. Baseline cognitive status did not moderate
      antidepressant treatment response. CONCLUSIONS: Although there are other cogent
      reasons why SSD in schizophrenia warrant direct intervention, treatment does not
      substantially affect the level of cognitive functioning. Given the effects of
      cognitive deficits associated with schizophrenia on functional disability, there
      remains an ongoing need to identify effective means of directly ameliorating
      them.

PMID- 22456095
TI  - Effects of women's body mass index on in vitro fertilization success: a
      retrospective cohort study.
AB  - BACKGROUND: The purpose of this study is to evaluate the influence of body mass
      index (BMI) on the reproductive outcomes and clinical pregnancy rate after in
      vitro fertilization (IVF). METHODS: This retrospective study was performed on 230
      women undergoing first cycle of standard IVF between October 2008 and February
      2010. The patients were classified into three groups according to their BMI (BMI
      < 20 kg/m2, 20 kg/m2 < BMI < 27.9 kg/m2 and BMI > 28 kg/m2). Information
      regarding clinical pregnancy was compared within these three groups. RESULTS:
      There was no significant relation between BMI and age, the number of aspirated
      follicles, transferred embryos, mature oocytes, days of taking human menopausal
      gonadotropin (HMG) ampules and the total number of HMG ampules among three BMI
      studied groups. Statistically significant difference was detected between BMI and
      endometrial thickness. CONCLUSIONS: BMI has no effect on IVF outcomes and
      clinical pregnancy after IVF. However, losing weight in obese women seems
      reasonable to prevent possible obstetrics complications.

PMID- 22456096
TI  - Long period grating based biosensor for the detection of Escherichia coli
      bacteria.
AB  - In this paper we report a stable, label-free, bacteriophage-based detection of
      Escherichia coli (E. coli) using ultra sensitive long-period fiber gratings
      (LPFGs). Bacteriophage T4 was covalently immobilized on optical fiber surface and
      the E. coli binding was investigated using the highly accurate spectral
      interrogation mechanism. In contrast to the widely used surface plasmon resonance
      (SPR) based sensors, no moving part or metal deposition is required in our
      sensor, making the present sensor extremely accurate, very compact and cost
      effective. We demonstrated that our detection mechanism is capable of reliable
      detection of E. coli concentrations as low as 10(3)cfu/ml with an experimental
      accuracy greater than 99%.

PMID- 22456097
TI  - A quantitative study of detection mechanism of a label-free impedance biosensor
      using ultrananocrystalline diamond microelectrode array.
AB  - It is well recognized that label-free biosensors are the only class of sensors
      that can rapidly detect antigens in real-time and provide remote environmental
      monitoring and point-of-care diagnosis that is low-cost, specific, and sensitive.
      Electrical impedance spectroscopy (EIS) based label-free biosensors have been
      used to detect a wide variety of antigens including bacteria, viruses, DNA, and
      proteins due to the simplicity of their detection technique. However, their
      commercial development has been hindered due to difficulty in interpreting the
      change in impedance upon antigen binding and poor signal reproducibility as a
      result of surface fouling and non-specific binding. In this study, we develop a
      circuit model to adequately describe the physical changes at bio functionalized
      surface and provide an understanding of the detection mechanism based on electron
      exchange between electrolyte and surface through pores surrounding antibody
      antigen. The model was successfully applied to extract quantitative information
      about the bio surface at different stages of surface functionalization. Further,
      we demonstrate boron-doped ultrananocrystalline diamond (UNCD) microelectrode
      array (3 * 3 format, 200 MUm diameter) improves signal reproducibility
      significantly and increases sensitivity by four orders of magnitude. This study
      marks the first demonstration of UNCD array based biosensor that can reliably
      detect a model Escherichia coli K12 bacterium using EIS, positioning this
      technology for rapid adoption in point-of-use applications.

PMID- 22456098
TI  - Altered face inversion effect and association between face N170 reduction and
      social dysfunction in patients with schizophrenia.
AB  - OBJECTIVE: There is accumulating evidence that schizophrenics may have deficits
      in facial recognition, which has been related to disease-specific disturbances in
      normal social interaction. Neurophysiologically, face inversion results in an
      amplitude increase of the event-related potential (ERP) component N170. This face
      inversion effect (FIE) presumably reflects a disruption of face-specific
      configuration processing. The present study investigated FIE and the associations
      between social functioning and N170 in patients with schizophrenia. METHODS: The
      subjects consisted of 15 schizophrenics and 15 controls. Event-related potentials
      (ERPs) to upright and inverted neutral faces and cars were recorded. The
      relationships between the Social Functioning Scale (SFS) scores and N170
      amplitude to upright faces or cars were also evaluated. RESULTS: Normal controls
      exhibited a significant FIE of the N170 amplitude, while schizophrenics showed no
      FIE. In both normal controls and schizophrenics, no inversion effect was observed
      for car stimuli. For face stimuli, schizophrenics showed significant bilateral
      N170 reduction; additionally, in schizophrenics, but not in controls, the SFS was
      significantly correlated with N170 amplitudes to upright faces. CONCLUSIONS:
      These results indicate face-specific configuration processing deficits and
      significant associations between face-N170 reduction and social dysfunction in
      schizophrenia. SIGNIFICANCE: Abnormal face-specific configuration processing may
      underlie some of the social dysfunctions in schizophrenia.

PMID- 22456099
TI  - Effects of aqueous polymeric surfactants on silicone-hydrogel soft- contact-lens
      wettability and bacterial adhesion of Pseudomonas aeruginosa.
AB  - Prevention of Pseudomonas aeruginosa binding to soft-contact lenses (SCLs) may
      curtail sight-threatening microbial keratitis. Substrate surface wettability is
      known to modulate adhesion of P. aeruginosa. This study investigates the use of
      aqueous alkoxylate block co-polymer surfactants for enhanced wettability and
      antibacterial adhesion of SCLs under leaching conditions. Specifically,
      Pluronic((r)) F127 (PF) and three ethylene oxide-butylene oxide (EOBO)
      surfactants were studied with four commercially available silicone-hydrogel
      contact lenses: Pure VisionTM, Acuvue AdvanceTM, Acuvue OasysTM and O(2)OptixTM.
      Dilute aqueous PF and EOBO surfactants impregnated all four soft-contact lenses,
      as demonstrated by surface-tension decline for leached surfactant. For PF
      surfactant, significant surface-wettability improvement upon rinsing occurred
      only after overnight leaching. EOBO surfactant showed a similar pattern with
      O(2)OptixTM lenses. EOBO-pretreated Pure VisionTM lenses, however, showed fast
      leaching and a significant change in surface energy towards improved wettability.
      Adhesion assays of P. aeruginosa displayed a small decrease in the binding rate
      of PAK bacteria for EOBO-pretreated Pure VisionTM lenses, but not for EOBO
      pretreated O(2)OptixTM lenses. P. aeruginosa strain-PAO1 bacteria adhesion to all
      lenses was independent of surface wettability. Despite the ability of polymeric
      surfactants to lower advancing contact angles under leaching conditions,
      increased lens wettability is not a universal panacea for antifouling of soft
      contact lenses.

PMID- 22456100
TI  - Incidence and risk factors for acute kidney injury in HIV Infection.
AB  - BACKGROUND/AIMS: Although HIV-infected persons are at higher risk for acute
      kidney injury (AKI) during hospitalization compared with their uninfected
      counterparts, risk factors for AKI are not well-defined. We aimed to describe the
      evolving incidence of AKI among HIV-infected individuals and to identify
      important AKI risk factors. METHODS: We conducted a prospective cohort study of
      56,823 HIV-infected persons in the Department of Veterans Affairs Clinical Case
      Registry. Outcomes were: AKI (acute in-hospital serum creatinine increase of
      >=0.3 mg/dl, or a relative increase by 50% or greater), and dialysis-requiring
      AKI. We used proportional hazards regressions to identify risk factors. RESULTS:
      From its peak in 1995 at 62 per 1,000 person-years, the incidence of AKI declined
      after the introduction of highly active antiretroviral therapy (HAART) in 1996 to
      a low point of 25 per 1,000 person-years in 2006. Incidence of dialysis-requiring
      AKI declined in the early 1990s, but doubled between 2000 and 2006. Using
      multivariate proportional hazard regression, we identified the following strong
      risk factors for AKI: chronic kidney disease (eGFR <60 ml/min/1.73 m(2)) (5.38,
      95% CI: 5.11-5.67), proteinuria (1.78, 1.70-1.87), low serum albumin (<3.7 mg/dl)
      (5.24, 4.82-5.71), low body mass index (<18.5 kg/m(2)) (1.69, 1.54-1.86),
      cardiovascular disease (1.77, 1.66-1.89), low CD4 count (<200 cells/mm(3)) (2.54,
      2.33-2.77), and high viral load (>=100,000 copies/ml) (2.51, 2.28-2.75). In
      addition, there was substantial heterogeneity in the strengths of risk factors
      for dialysis-requiring AKI before and after the introduction of HAART.
      CONCLUSIONS: Although AKI incidence has decreased during the HAART era, it
      remains common in HIV-infected persons and appears attributable to both kidney-
      and HIV-related factors.

PMID- 22456101
TI  - Heroin-induced chronic symmetrical skin ulcers of the forearms in a young adult.

PMID- 22456102
TI  - Structure of lipid A from a stem-nodulating bacterium Azorhizobium caulinodans.
AB  - The structure of the lipid A of the lipopolysaccharide (LPS) from Azorhizobium
      caulinodans, a symbiont of the tropical legume Sesbania rostrata, was
      investigated by chemical compositional analyses, mass spectrometry, as well as 1D
      and 2D NMR spectroscopy techniques. The lipid A backbone was composed of a beta
      (1->6)-linked 2,3-diamino-2,3-dideoxy-D-glucopyranose (GlcpN3N) disaccharide and
      alpha-D-glucuronic acid (GlcpA). Nuclear magnetic resonance spectroscopy revealed
      that the GlcpA was connected to the reducing end of the diaminosugar disaccharide
      via an alpha-(1->1) glycosidic bond. The lipid A was deprived of phosphate
      residues. ESI-MS analysis showed that the lipid A preparation was a mixture of
      molecules due to the occurrence of different acylation patterns. The GlcpN3N
      disaccharide backbone was N-acylated at the C-2, C-3, C-2' and C-3' positions
      with 3-OH-18:0, 3-OH-14:0, 3-OH-20:1 and 3-OH-14:0 fatty acids, respectively.
      Nonpolar fatty acids as well as 3-OH-18:0 were found to be ester-linked. They
      were attached to hydroxyl groups of primary 3-OH fatty acids giving three
      acyloxyacyl moieties. Thus, the complete lipid A from A. caulinodans comprised
      seven acyl residues. Part of the lipid A molecules was esterified by 3
      methoxybutyric acid. Azorhizobium caulinodans did not incorporate omega-1
      hydroxylated very long chain fatty acids (e.g., 27-OH-28:0) into the lipid A,
      which makes this variant of endotoxin unusual among rhizobial lipids A.

PMID- 22456103
TI  - Effect of cultured autologous oral keratinocyte suspension in fibrin glue on oral
      wound healing in rabbits.
AB  - The effect of cultured autologous oral keratinocyte suspension in fibrin glue on
      the healing of surgically produced oral mucosal wounds was assessed in the rabbit
      model. Using the light microscope and a digital image analysis system, the
      epithelization parameters (marginal epithelization and percentage of wound re
      epithelization) were measured in haematoxylin-eosin stained sections of the wound
      area and compared with those of wounds treated with fibrin glue alone and
      untreated ones. The epithelization was significantly higher in keratinocytes plus
      fibrin glue-treated wounds on postoperative days 3 and 7. No significant
      differences were observed on postoperative day 1, when the healing process had
      just begun, and on postoperative day 14, when re-epithelization was completed or
      nearly completed in all groups. The inflammatory infiltration of the wounded
      mucosa was weakest in keratinocyte-treated wounds and strongest in untreated
      wounds. In conclusion, suspension of cultured autologous oral keratinocytes in
      fibrin glue significantly accelerates oral wound healing in the rabbit model and
      could be beneficial in the treatment of oral wounds in patients.

PMID- 22456104
TI  - Facial mimicry after conservative parotidectomy: a three-dimensional
      optoelectronic study.
AB  - Facial nerve paralysis is one of several possible complications following
      conservative parotidectomy. To assess three-dimensional facial movements non
      invasively in patients with unilateral facial palsy following parotidectomy for
      benign tumours, the three-dimensional coordinates of 21 soft-tissue facial
      landmarks were recorded in 32 patients (21 HB I, 5 HB II, 6 HB III-IV; 3 months
      post-surgery follow-up), and 40 control subjects, during the performance of
      facial movements (smile, 'surprise', eye closure, single eye closure). For all
      symmetric animations, control subjects had larger total mobility than patients;
      mobility progressively decreased in patients with larger clinical grades. For
      asymmetric eye closures, HB I patients and control subjects had similar total
      movements, while HB II patients had smaller movements, especially for the paretic
      side eye closure; smaller total movements were found in HB III-IV patients. The
      method allowed the quantitative detection of alterations in facial movements.
      Significant differences between patients and control subjects in the magnitude
      and asymmetry of movements were found.

PMID- 22456105
TI  - Ejaculatory abstinence influences intravaginal ejaculatory latency time: results
      from a prospective randomized trial.
AB  - INTRODUCTION: The relationship between ejaculatory frequency and ejaculatory
      latency time is under-investigated. SUBJECTS AND METHODS: 120 healthy subjects
      were enrolled in a prospective randomized trial. Patients in group A engaged in
      sexual intercourse after a 10-day abstinence period for 3 months. Patients in
      group B engaged in sexual intercourse twice a week for 3 months. Ejaculation
      function was evaluated through the measurement of the intravaginal ejaculatory
      latency time (IELT) and through the premature ejaculation diagnostic tool (PEDT)
      at baseline and at the end of the study. RESULTS: At the end of the study, mean
      IELT values in group A were significantly lower compared to baseline values.
      Results from the PEDT questionnaire at the end of the study demonstrated a
      significantly worse ejaculatory control and ability to delay ejaculation by
      patients in group A. CONCLUSIONS: Reduced ejaculatory frequency impairs
      ejaculation control.

PMID- 22456106
TI  - Tinzaparin is safe and effective in the management of hemodialysis catheter
      thrombosis.
AB  - Children on hemodialysis are at increased risk of thrombosis, especially when
      dialyzed via a central venous catheter (CVC); there are limited published data
      regarding the safety and efficacy of tinzaparin in this group. We conducted a
      retrospective chart review of all children in the National Pediatric Hemodialysis
      Centre for Ireland diagnosed with a CVC thrombus and treated with subcutaneous
      tinzaparin over a 10 year period. Seven children were treated with subcutaneous
      tinzaparin for 10 CVC thrombi. Tinzaparin was commenced at 175 IU/kg/day and the
      dose was titrated by measuring anti-factor Xa levels, aiming for levels of 0.3
      1.0 IU/ml. Treatment was continued until resolution of the CVC thrombus.
      Restoration of normal flows during dialysis occurred within 3 days in all
      patients. There were no episodes of bleeding and all children tolerated the
      treatment well.

PMID- 22456107
TI  - MicroRNA-372 is associated with poor prognosis in colorectal cancer.
AB  - OBJECTIVE: MicroRNA-372 (miR-372) is reportedly shown to be an oncogene in human
      testicular germ cell tumors and gastric cancers, but its expression in colorectal
      cancer (CRC) is not yet determined. This study investigated the clinical
      significance of miR-372 expression in CRC. METHODS: qRT-PCR was used to evaluate
      miR-372 in 144 CRC patients, and large tumor suppressor 2 (LATS2) expression was
      also examined as the likely target gene of miR-372. In vitroassays were performed
      to evaluate the biological function of miR-372. RESULTS: Multivariate analysis
      indicated that high miR-372 expression was an independent prognostic factor (p =
      0.006). High miR-372 expression was associated with synchronous liver metastasis
      (p = 0.035). We found an inverse relationship between miR-372 and LATS2 by qRT
      PCR (p = 0.007) and immunohistochemistry (p = 0.042) using CRC tissue samples.
      Furthermore, pre-miR-372 led to a decrease in the LATS2 protein and an increase
      in proliferative activity of LoVo cells. We also found a significant association
      between low LATS2 expression and liver metastasis (p = 0.042). CONCLUSIONS: This
      study suggested that miR-372 was a novel independent prognostic factor in CRC.
      Our data suggest that LATS2 may serve as one of the target genes of miR-372 in
      clinical CRC tissues.

PMID- 22456108
TI  - Subthalamic deep brain stimulation modulates small fiber-dependent sensory
      thresholds in Parkinson's disease.
AB  - The effects of deep brain stimulation of the subthalamic nucleus on nonmotor
      symptoms of Parkinson's disease (PD) rarely have been investigated. Among these,
      sensory disturbances, including chronic pain (CP), are frequent in these
      patients. The aim of this study was to evaluate the changes induced by deep brain
      stimulation in the perception of sensory stimuli, either noxious or innocuous,
      mediated by small or large nerve fibers. Sensory detection and pain thresholds
      were assessed in 25 PD patients all in the off-medication condition with the
      stimulator turned on or off (on- and off-stimulation conditions, respectively).
      The relationship between the changes induced by surgery on quantitative sensory
      testing, spontaneous CP, and motor abilities were studied. Quantitative sensory
      test results obtained in PD patients were compared with those of age-matched
      healthy subjects. Chronic pain was present in 72% of patients before vs 36% after
      surgery (P=.019). Compared with healthy subjects, PD patients had an increased
      sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced
      sensitivity to innocuous mechanical stimuli. In addition, they had an increased
      pain rating when painful thermal stimuli were applied, particularly in the off
      stimulation condition. In the on-stimulation condition, there was an increased
      sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical
      or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator
      was turned on. Motor improvement positively correlated with changes in warm
      detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation
      contributes to relieve pain associated with PD and specifically modulates small
      fiber-mediated sensations.

PMID- 22456109
TI  - Analysis of footprint and its parts for stature estimation in Indian population.
AB  - BACKGROUND: Most often, forensic podiatrists are called upon in crime scene
      investigations where pedal evidence is encountered at the crime scenes. The main
      aim of the forensic podiatrist is such case is to contribute towards the
      establishment of the identity of the suspects on the basis of the evidence. One
      form of the pedal evidence is footprints that are often recovered at the crime
      scenes. Estimation of stature from footprints forms a major parameter of personal
      identification in forensic examinations. OBJECTIVES: The main aim of the present
      study is to make stature estimation standards based on detailed analysis of
      length measurements of footprints in Indian population using statistical
      considerations. METHODS: A sample of 100 young adults (50 males and 50 females)
      was included in the study conducted at the Department of Forensic Medicine,
      Kasturba Medical College, Mangalore, India. Footprints were obtained from both
      the feet of each subject. Besides stature, five length measurements i.e. T1, T2,
      T3, T4 and T5 were measured on both the footprints of each subject using
      international standards. Bilateral asymmetry in the measurements on footprints
      was calculated and tested using paired t-test. Pearson's correlation coefficients
      were calculated between stature and various footprint length measurements and the
      stature was estimated using linear and multiple regression analysis. RESULTS: Our
      study observes a statistically significant sex difference (p<0.001) in the
      footprint length measurements between males and females in both right and left
      feet. A positive and strong correlation exists between various length
      measurements of the footprint and stature in both the sexes. Males show
      relatively higher values of correlation coefficients than females. Bilateral
      differences (right-left differences) were also observed in some of the footprint
      length measurements among males and females. Linear and multiple regression
      models are derived for estimation of stature from various footprint length
      measurements in males, females and for the pooled sample. CONCLUSIONS: The
      footprints can provide a reliable estimate of stature in forensic investigations.
      Sex specific regression models give a more accurate estimate of stature than the
      pooled sample.

PMID- 22456110
TI  - Prevalence of restless legs syndrome in runners.

PMID- 22456111
TI  - Defining the borders between Sleep-Related Eating Disorder and Night Eating
      Syndrome.
AB  - OBJECTIVES: Nocturnal eating is a common symptom of two clinical conditions with
      different pathogenesis and needing different therapeutic approaches: Sleep
      Related Eating Disorder (SRED) and Night Eating Syndrome (NES). The first is
      considered a parasomnia while the second is an eating disorder; however, the
      distinction between SRED and NES is still a controversial matter. The aim of this
      study was to better define psychological, behavioral, and polysomnographic
      characteristics of the two syndromes. METHODS: An eating disorders' specialist
      tested a group of 28 nocturnal eaters diagnosed as affected by SRED by a sleep
      expert, following the current criteria of the international classification of
      sleep disorders, to find out if any of them was affected by NES according to the
      criteria suggested by both sleep and eating disorders specialists during the
      first international meeting on Night Eating Syndrome (Minneapolis, 2009) and if
      they had specific psychological or polysomnographic characteristics. RESULTS:
      Twenty-two subjects were diagnosed to be affected by NES. They scored higher on
      the physical tension subscale of the Sleep Disturbance Questionnaire (SDQ) and on
      the mood and sleep subscale of the Night Eating Questionnaire (NEQ), but there
      were no other significant differences between SRED and NES patients nor for age,
      Body Mass Index (BMI), or gender distribution. CONCLUSIONS: The overlap between
      the symptomatology and the polysomnographic characteristics of the two
      pathologies and the difficulty in making a differential diagnosis between NES and
      SRED indicate the need for an update of the diagnostic criteria for SRED, as was
      recently done for NES.

PMID- 22456112
TI  - Preference-based SF-6D scores derived from the SF-36 and SF-12 have different
      discriminative power in a population health survey.
AB  - OBJECTIVE: To compare the discriminative power of the SF-6D index scores derived
      from the SF-36 (SF-6D36) and SF-12 (SF-6D12) in the general population. METHODS:
      Data from the National Health Measurement Study were used. The F statistic was
      used to compare the relative efficiency of the SF-6D36 and SF-6D12, as well as
      the EQ-5D, HUI2, and HUI3 index scores, in discriminating between respondents
      with and without 1 of the 11 chronic medical conditions. The efficiency of the
      multiattribute health classification systems of the study instruments was
      measured using the Shannon index (H'). The relative efficiency of the SF-6D36 and
      SF-6D12 was also compared in respondents who were on the ceilings of the EQ-5D,
      HUI2, and HUI3 scales. RESULTS: The SF-6D36 score was systematically lower than
      the SF-6D12 score at the group level (range, 0.022-0.036). The SF-6D36 exhibited
      higher discriminative power in 8 and 5 conditions than the SF-6D12 and all other
      index scores, respectively. The SF-6D36 had higher H' values than the SF-6D12 in
      the dimensions of physical functioning (1.73 vs. 0.78), mental health (1.70 vs.
      1.39), and bodily pain (2.16 vs. 1.56) as well as than all other instruments in
      similar health dimensions. In respondents reporting full health on the EQ-5D,
      HUI2, or HUI3, the SF-6D36 better discriminated between those with and without
      medical conditions than the SF-6D12. CONCLUSIONS: The SF-6D derived from the SF
      36 is more discriminative than that derived from the SF-12 and is therefore
      preferred for use in population health surveys where a preference-based health
      index is needed.

PMID- 22456113
TI  - Regional associations between Medicare Advantage penetration and administrative
      claims-based measures of hospital outcomes.
AB  - BACKGROUND: Risk-standardized measures of hospital outcomes reported by the
      Centers for Medicare and Medicaid Services include Medicare fee-for-service (FFS)
      patients and exclude Medicare Advantage (MA) patients due to data availability.
      MA penetration varies greatly nationwide and seems to be associated with
      increased FFS population risk. Whether variation in MA penetration affects the
      performance on the Centers for Medicare and Medicaid Service measures is unknown.
      OBJECTIVE: To determine whether the MA penetration rate is associated with
      outcomes measures based on FFS patients. RESEARCH DESIGN: In this retrospective
      study, 2008 MA penetration was estimated at the Hospital Referral Region (HRR)
      level. Risk-standardized mortality rates and risk-standardized readmission rates
      for heart failure, acute myocardial infarction, and pneumonia from 2006 to 2008
      were estimated among HRRs, along with several markers of FFS population risk.
      Weighted linear regression was used to test the association between each of these
      variables and MA penetration among HRRs. RESULTS: Among 304 HRRs, MA penetration
      varied greatly (median, 17.0%; range, 2.1%-56.6%). Although MA penetration was
      significantly (P<0.05) associated with 5 of the 6 markers of FFS population risk,
      MA penetration was insignificantly (P>=0.05) associated with 5 of 6 hospital
      outcome measures. CONCLUSION: Risk-standardized mortality rates and risk
      standardized readmission rates for heart failure, acute myocardial infarction,
      and pneumonia do not seem to differ systematically with MA penetration, lending
      support to the widespread use of these measures even in areas of high MA
      penetration.

PMID- 22456114
TI  - Elevated plasma levels of endostatin are associated with chronic kidney disease.
AB  - BACKGROUND/AIMS: Angiogenesis may play an important role in the renal repair
      process after injury. We investigated the association between plasma endostatin,
      an endothelial-specific antiangiogenic factor, and chronic kidney disease (CKD).
      METHODS: We compared plasma endostatin levels in 201 CKD patients and 201
      controls. CKD was defined as estimated glomerular filtration rate (eGFR) <60
      ml/min/1.73 m(2) or presence of albuminuria (>=30 mg/24 h). RESULTS: After
      adjustment for established CKD risk factors, the median (interquartile range) of
      plasma endostatin was 276.7 ng/dl (199.3-357.5) in patients with CKD and 119.4
      ng/dl (103.7-134.6) in controls without CKD (p < 0.0001 for group difference).
      log-transformed plasma endostatin was significantly and inversely correlated with
      eGFR (r = -0.83, p < 0.0001) and positively correlated with log-transformed urine
      albumin (r = 0.66, p < 0.0001) in the study participants. In addition, one
      standard deviation increase in log-transformed plasma endostatin (0.55 ng/dl) was
      associated with a decline in eGFR of -26.2 ml/min and an increase in urine
      albumin of 3.26 mg/ 24 h after adjusting for multiple covariables. Furthermore,
      the multivariable-adjusted odds ratio for CKD comparing the highest tertile
      (>=131.4 ng/dl) to the two lower tertiles of plasma endostatin was 21.6 (95% CI:
      10.2-45.5; p < 0.0001). CONCLUSION: These data indicate that elevated plasma
      endostatin is strongly and independently associated with CKD. Prospective cohort
      studies and clinical trials are warranted to further examine the causal
      relationship between endostatin and risk of CKD and to develop novel
      interventions targeting circulating endostatin aimed at reducing CKD risk.

PMID- 22456116
TI  - Clinical significance of serum decoy receptor 3 levels in patients with systemic
      sclerosis.
AB  - Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis
      in certain pathological conditions. We herein measured serum DcR3 levels in 51
      patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated
      their clinical significance in this disorder. Serum DcR3 levels were
      significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited
      cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were
      significantly elevated in patients with disease duration of <=6 years compared
      with healthy controls, but not in those with disease duration of >6 years. Serum
      DcR3 levels correlated negatively with the percentage of predicted diffusion lung
      capacity for carbon monoxide and positively with right ventricular systolic
      pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive
      protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the
      elevation of serum DcR3 levels is associated with the development of pulmonary
      arterial hypertension and systemic inflammation in SSc.

PMID- 22456117
TI  - The tangled web of non-canonical Wnt signalling in neural migration.
AB  - In all multicellular animals, successful embryogenesis is dependent on the
      ability of cells to detect the status of the local environment and respond
      appropriately. The nature of the extracellular environment is communicated to the
      intracellular compartment by ligand/receptor interactions at the cell surface.
      The Wnt canonical and non-canonical signalling pathways are found in the most
      primitive metazoans, and they play an essential role in the most fundamental
      developmental processes in all multicellular organisms. Vertebrates have expanded
      the number of Wnts and Frizzled receptors and have additionally evolved novel Wnt
      receptor families (Ryk, Ror). The multiplicity of potential interactions between
      Wnts, their receptors and downstream effectors has exponentially increased the
      complexity of the signal transduction network. Signalling through each of the Wnt
      pathways, as well as crosstalk between them, plays a critical role in the
      establishment of the complex architecture of the vertebrate central nervous
      system. In this review, we explore the signalling networks triggered by non
      canonical Wnt/receptor interactions, focussing on the emerging roles of the non
      conventional Wnt receptors Ryk and Ror. We describe the role of these pathways in
      neural tube formation and axon guidance where Wnt signalling controls tissue
      polarity, coordinated cell migration and axon guidance via remodelling of the
      cytoskeleton.

PMID- 22456118
TI  - State cigarette excise taxes - United States, 2010-2011.
AB  - Increasing the price of cigarettes reduces the demand for cigarettes, thereby
      reducing youth smoking initiation and cigarette consumption and decreasing the
      prevalence of cigarette use in the United States overall, particularly among
      youths and young adults. The most common way governments have increased the price
      of cigarettes is by increasing cigarette excise taxes, which currently are
      imposed by all states and the District of Columbia. To update data on state
      cigarette excise taxes in 2009, CDC conducted a survey of changes in state
      cigarette excise taxes during 2010-2011. During that period, eight states
      increased their cigarette excise taxes, and one state decreased its tax; as a
      result, the mean state tax increased from $1.34 in 2009 to $1.46 in 2011.
      Previous evidence indicates that further increases in cigarette excise taxes
      would be expected to result in further reductions in demand for cigarettes,
      decreasing smoking and associated morbidity and mortality.

PMID- 22456119
TI  - The epidemiology workforce in state and local health departments - United States,
      2010.
AB  - During 2001-2009, the Council of State and Territorial Epidemiologists (CSTE)
      conducted four epidemiology capacity assessments (ECAs) in state and territorial
      public health departments in the United States. In October 2010, CSTE sent a
      follow-up, Internet-based questionnaire to the state epidemiologist in each of
      the 50 states and the District of Columbia. The purpose was to enumerate the
      state-level epidemiology workforce and determine whether it had varied since 2009
      because of changes in state and federal funding and, for the first time, to
      estimate concurrently the number of epidemiologists working in local health
      departments using the same definition for local health department epidemiologist
      as for state-level epidemiologist. A total of 3,754 epidemiologists working in
      state and local health departments were reported: 2,476 (66%) at the state level
      and 1,278 (34%) at the local level, the latter number consistent with results of
      several recent surveys. The state-level epidemiology workforce increased 12.9%
      during the 18 months since the previous assessment. Although 63% of states
      reported fewer state-funded positions, only 24% reported fewer federally funded
      positions. Federal stimulus funding might have helped preserve and enhance the
      state-level epidemiology workforce. Future epidemiology workforce assessments
      should include both the state and local epidemiology workforce, possibly through
      CSTE coordination with the National Association of County and City Health
      Officials and other agencies.

PMID- 22456120
TI  - Caterpillar-associated rashes in children - Hillsborough County, Florida, 2011.
AB  - In March and April 2011, the Hillsborough County Health Department (HCHD)
      Epidemiology Department (Tampa, Florida) investigated three clusters of rash
      illness linked to the white-marked tussock moth caterpillar among persons at two
      child care centers and one elementary school. At least 23 children and one adult
      were affected; most had direct contact with caterpillars. HCHD provided
      recommendations on treatment and preventing caterpillar exposure to the three
      facilities, health-care providers, and local agencies, and through local news
      media. Child care centers and elementary schools in Hillsborough County
      previously have experienced caterpillar-associated rash outbreaks in 2004 and
      2005. Awareness of this problem, particularly during periods of caterpillar
      infestation, can minimize morbidity and help to avoid inappropriate diagnoses and
      treatment by health-care providers.

PMID- 22456121
TI  - FDA approval of an extended period for administering VariZIG for postexposure
      prophylaxis of varicella.
AB  - VariZIG (Cangene Corporation, Winnipeg, Canada) is the only varicella zoster
      immune globulin preparation available in the United States for postexposure
      prophylaxis of varicella in persons at high risk for severe disease who lack
      evidence of immunity to varicella and are ineligible for varicella vaccine.
      VariZIG is available in the United States through an investigational new drug
      (IND) application expanded access protocol. VariZIG is a purified immune globulin
      preparation made from human plasma containing high levels of anti-varicella
      zoster virus antibodies (immunoglobulin G). In May 2011, the Food and Drug
      Administration (FDA) approved an extended period for administering VariZIG. The
      period after exposure to varicella zoster virus during which a patient may
      receive VariZIG, which had been 96 hours (4 days), is now 10 days. VariZIG should
      be administered as soon as possible after exposure.

PMID- 22456122
TI  - Notes from the field: severe hand, foot, and mouth disease associated with
      coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 2011
      February 2012.
AB  - Hand, foot, and mouth disease (HFMD) is a common viral illness caused by
      enteroviruses that predominantly affects children aged <5 years. In the United
      States, outbreaks of HFMD typically occur during summer and autumn months. The
      most common cause of HFMD in the United States has been enterovirus serotype
      coxsackievirus A16. Most infections are asymptomatic; persons with signs and
      symptoms typically have a mild febrile illness with rash on the palms of the
      hands and soles of the feet, and sores in the mouth. HFMD also has been
      associated, often weeks after initial symptom onset, with nail dystrophies (e.g.,
      Beau's lines or nail shedding).

PMID- 22456123
TI  - Comparison of nephrostomy drainage types. Re: Comparison of nephrostomy drainage
      types following percutaneous nephrolithotomy requiring multiple tracts: single
      tube versus multiple tubes versus tubeless [Urol Int 2011;87:23-27].

PMID- 22456125
TI  - Writing is part of  medicine.

PMID- 22456124
TI  - Activation of the sonic hedgehog pathway and its prognostic impact in patients
      with gastric cancer.
AB  - BACKGROUND: The sonic hedgehog (SHH) signaling pathway is critical in fetal
      organogenesis. Activation of the SHH pathway has been associated with several
      types of human cancer; however, the clinical impact of SHH activation in patients
      with gastric cancer is still unknown. METHODS: The present study included 41
      patients with gastric cancer who underwent gastrectomy between 2000 and 2004.
      SHH, Patched-1 (PTCH1), Smoothened (SMO) and Glioma-associated oncogene-1 (GLI1)
      were examined immunohistochemically, and these of mRNAs from the cancer lesions
      were evaluated using real-time quantitative RT-PCR. RESULTS: Immunohistological
      expressions of SHH-related molecules were relatively intense in cancer tissue,
      but no significant correlation was found with any clinicopathological factors of
      tumor. PTCH1 was only the molecule associated with poor prognosis of patients
      with differentiated type of tumor. For mRNA analysis, a significant correlation
      was demonstrated between certain clinicopathological factors and PTCH1, SMO
      or/and GLI1 mRNA levels. High levels of SHH and PTCH1 mRNA were associated with
      poor prognosis. Multivariate analysis demonstrated the PTCH1 mRNA level and liver
      metastasis as significant independent prognostic factors. CONCLUSIONS: PTCH1
      expression in the SHH pathway was possibly involved in gastric cancer tumor
      progression, and could be a useful indicator for the prognosis of gastric cancer.

PMID- 22456126
TI  - [Malaria treatment--herbal therapy in new clothes].

PMID- 22456127
TI  - [Difficult prioritizations].

PMID- 22456128
TI  - [Measurement methods in questionnaire studies].

PMID- 22456129
TI  - [Expertise in the supreme court].

PMID- 22456131
TI  - [Afraid of patient experiences].

PMID- 22456132
TI  - [Necessary power shift].

PMID- 22456133
TI  - [Adverse treatment].

PMID- 22456134
TI  - [If Earth was our patient].

PMID- 22456135
TI  - [Oral application of chlorhexidine prevents pneumonia in intubated patients].

PMID- 22456136
TI  - Internal quality register  for joint prostheses.

PMID- 22456137
TI  - Pedagogical training  for health personnel.

PMID- 22456138
TI  - [Neuroma in clitoris after circumcision].

PMID- 22456139
TI  - [The right of reservation is necessary].

PMID- 22456140
TI  - [What is an intensive Department of Internal Medicine?].

PMID- 22456141
TI  - [Totally drug resistant tuberculosis?].

PMID- 22456142
TI  - [Physician's responsibility or loss of authorization].

PMID- 22456143
TI  - [What is evidence-based advice?].

PMID- 22456144
TI  - Intestinal and multivisceral  transplantation in patients with chronic intestinal
      failure.
AB  - BACKGROUND: Patients with chronic intestinal failure are treated primarily with
      parenteral nutrition, often for many years. If serious complications arise for
      intravenous nutritional therapy, it is possible to perform intestinal or multi
      organ transplantation in selected patients. We have established a collaboration
      with Professor Michael Olausson at Sahlgrenska University Hospital in Gothenburg
      and Professor Andreas Tzakis at the Jackson Memorial Hospital in Miami, USA, to
      provide an option for Norwegian patients with chronic intestinal failure.
      MATERIAL AND METHOD: Retrospective long-term study of seven patients (five in
      Gothenburg and two in Miami) with chronic intestinal failure who underwent
      intestinal or multi-organ transplantation (ventricle, duodenum, pancreas and
      small intestine) in the period 2001-2009. At the same time, liver and kidney
      transplantations were performed on six and two patients, respectively. RESULTS:
      Four of seven patients are alive and have a good quality of life 24-120 months
      after the transplantation. The graft function is satisfactory, so that the
      patients' food intake is mainly oral. Three patients died following a serious
      infection one, ten and 24 months, respectively, after transplantation took place.
      INTERPRETATION: Intestinal and multi-organ transplantation is a demanding and
      expensive treatment. Life-long multi-disciplinary follow-up of the patients is
      necessary after the transplantation in order to ensure early diagnosis of
      rejection and infections. Collaboration with international centres has given
      Norwegian patients with chronic intestinal failure an option of transplantation
      with satisfactory long-term results.

PMID- 22456145
TI  - Twelve years of "Case reports" in the Journal of the Norwegian Medical
      Association.
AB  - BACKGROUND: "Case reports" is the title of a column in the Journal of the
      Norwegian Medical Association devoted to educational patient histories
      accompanied by an expert commentary. The aim of this study is to describe the
      patients and authors in this column since its introduction in 1999. MATERIAL AND
      METHOD: The study is based on electronic literature searches in the Journal's
      internet archive (2000-2011) supplemented by manual searches in the printed
      edition (1999). The medical specialities of the authors were defined on the basis
      of their workplace affiliations. RESULTS: Literature searches identified 157 case
      reports and 157 accompanying commentaries that had been published in "Case
      reports". Of the 157 patients, 73 (46.0 %) were men and 84 (54.0 %) women aged 0
      90. The most frequently represented age group was 51-60 years. First authors were
      most often affiliated with departments of internal medicine with associated
      subspecialties (34.0 %), neurology (13.0 %), general surgery with subspecialties
      (11.0 %) and paediatrics (10.0 %). Paraclinical specialties, most frequently
      pathology and radiology, were mainly represented by co-authorships. Only 7 (1.0
      %) of a total of 676 authors were associated with psychiatry and 5 (0.7 %) with
      general practice. INTERPRETATION: The column "Case reports" has been illustrated
      through a period of 12 years by a wide range of patients, but the medical
      specialties are unevenly represented. It would be desirable to have more articles
      from specialties such as psychiatry and general practice.

PMID- 22456146
TI  - [Chronic inflammatory arthritis and pregnancy].
AB  - BACKGROUND: Chronic inflammatory arthritis often appears first in women of
      fertile age. Their pregnancies are considered to be of low risk compared with
      pregnancies in women with systemic inflammatory connective tissue disease.
      METHOD: The article is based on literature searches in PubMed for studies of the
      pregnancy outcomes of women with chronic inflammatory arthritis. Studies without
      a reference group or studies based on analyses of mixed populations of
      inflammatory arthritis and connective tissue disease patients were excluded.
      RESULTS: Recurrent findings in the published literature were: low mean birth
      weight, a higher proportion of children with a birth weight of less than 2500
      grams, children born small for gestational age, preterm births and a higher
      proportion of Caesarean sections. A high level of disease activity is associated
      with the risk of low birth weight and preterm birth. However, serious
      complications are not frequently reported. Glucocorticosteroids and disease
      modifying medicines such as sulphasalazine and hydroxychloroquine may be used
      during pregnancy. Non-steroidal anti-inflammatory drugs such as ibuprofen and
      naproxen may be used until gestational week 32. Methotrexate is contraindicated
      and must be terminated three months before conception. The TNF inhibitors
      adalimumab, etanercept and infliximab may be used until conception.
      INTERPRETATION: Pregnancy is seldom absolutely contraindicated for women with
      inflammatory arthritis. Pregnancy should be planned carefully and preferably be
      confined to periods with a low level of disease activity. First pregnancies
      require special attention. Interdisciplinary collaboration between
      rheumatologists and gynaecologists is recommended for monitoring patients with
      active arthritis.

PMID- 22456147
TI  - [Pseudoarthrosis after costal fracture].

PMID- 22456148
TI  - Treatment of malaria in  Norway.

PMID- 22456149
TI  - A fit man with fever  and pain in both thighs.

PMID- 22456150
TI  - Tourism, climate change and diagnostics.

PMID- 22456151
TI  - [A man in his 60's with acute headache].

PMID- 22456152
TI  - [The family physician system requires more physicians].

PMID- 22456153
TI  - Colleague Peter Andreas Munch.

PMID- 22456154
TI  - [Epilepsy in literature and film].

PMID- 22456155
TI  - [A literary varix].

PMID- 22456156
TI  - Sickness in the Nidaros Cathedral?

PMID- 22456157
TI  - New  cardiovascular hospital in Astrakhan, Russia.

PMID- 22456158
TI  - [I'm not a doctor anymore - what am I?].

PMID- 22456161
TI  - [Lazarus, lazaret and lazaron].

PMID- 22456164
TI  - Childhood and adult social conditions and risk of stroke.
AB  - BACKGROUND: Socioeconomic conditions may strongly influence the risk of stroke.
      We tested the hypotheses that indexes of social status in different life periods
      including childhood are inversely associated with stroke risk and that there is a
      cumulative effect of social conditions during lifetime on the risk of stroke.
      Furthermore, we investigated whether social advancement compared to the parental
      generation is associated with reduced stroke risk. METHODS: In a case-control
      study, we assessed parental professional status, highest school degree,
      professional education and the last professional activity in 370 consecutive
      patients with ischemic or hemorrhagic stroke or transient ischemic attack [TIA;
      age 60.7 +/- 12.8 years (mean +/- standard deviation); 31.1% women] and 370 age-
      and sex-matched control subjects randomly selected from the general population of
      the same area. RESULTS: Higher level of school exams [odds ratio (OR) 0.58, 95%
      confidence interval (CI) 0.39-0.86], university or polytechnic high school
      degrees (OR 0.39, 95% CI 0.24-0.63), nonmanual (last or current) professional
      activity (OR 0.51, 95% CI 0.37-0.71) and father's nonmanual professional activity
      (OR 0.64, 95% 0.43-0.97) were associated with a lower risk of stroke/TIA.
      Adjustment for vascular risk factors including current smoking and alcohol
      consumption reduced the strength of these associations and rendered them
      nonsignificant except for university or polytechnic high school degrees (OR 0.49,
      95% CI 0.27-0.87). Additional adjustment for regular sports activity further
      attenuated the association between academic degrees and risk of stroke/TIA (OR
      0.56, 95% CI 0.31-1.02). A score summarizing 4 lifetime social indexes was not
      independently associated with stroke risk (OR 0.67, 95% CI 0.39-1.16). Social
      advancement as assessed by changes from paternal manual work to nonmanual work in
      the index generation was more common among control subjects (23.5%) than patients
      (15.3%; p = 0.0097), but such advancement was not independently associated with
      stroke/TIA after adjustment for all covariables (OR 0.82, 95% CI 0.50-1.33).
      CONCLUSIONS: Socioeconomic conditions were inversely linked to the risk of
      stroke/TIA. These associations were strongly influenced by lifestyle factors such
      as smoking, alcohol consumption and mainly sports activity. Stroke preventive
      strategies may have a particularly large potential if they focus on such
      lifestyle habits in socially disadvantaged groups.

PMID- 22456165
TI  - Decisive role of SPECT/CT in localization of unusual periscapular sentinel nodes
      in patients with posterior trunk melanoma:  three illustrative cases and a review
      of the literature.
AB  - Sentinel node mapping is widely applied in patients with melanoma. Although this
      type of skin cancer usually drains to the standard regional nodal basins, some
      patients have drainage to an unpredicted site. Nodes lying along a lymphatic
      channel, between the primary melanoma site and a common basin, are often called
      interval, in-transit, ectopic, intercalated, or aberrant nodes. They must be
      considered sentinel lymph nodes because they receive direct lymphatic drainage
      from a primary tumor site. Most investigators agree that interval sentinel nodes
      should be harvested; however, the management of melanoma patients with an
      involved interval sentinel node without established metastasis in the regional
      basin downstream is controversial. New and innovating technologies have improved
      nuclear medicine images, including single-photon emission computed
      tomography/computed tomography (SPECT/CT), a multimodal technique that fuses the
      radioactivity distribution detected by SPECT with the anatomic information
      harvested by CT. SPECT/CT does not replace the conventional planar images; it
      should be considered as a complementary modality for the search of sentinel lymph
      nodes. We report three illustrative cases that underline the decisive role of
      SPECT/CT with two-dimensional and three-dimensional reconstruction images to
      localize the uncommon periscapular sentinel nodes in patients with melanoma of
      the posterior trunk. The use of this image fusion technique on these patients
      leads to improved preoperative visualization of the sentinel nodes, may help
      identify additional periscapular interval sentinel nodes, and enables precise
      localization of the nodes with their surrounding anatomic structures. The cases
      are discussed together with a review of the literature.

PMID- 22456166
TI  - Marked genetic differences between BRAF and NRAS mutated primary melanomas as
      revealed by array comparative genomic hybridization.
AB  - Somatic mutations of BRAF and NRAS oncogenes are thought to be among the first
      steps in melanoma initiation, but these mutations alone are insufficient to cause
      tumor progression. Our group studied the distinct genomic imbalances of primary
      melanomas harboring different BRAF or NRAS genotypes. We also aimed to highlight
      regions of change commonly seen together in different melanoma subgroups. Array
      comparative genomic hybridization was performed to assess copy number changes in
      47 primary melanomas. BRAF and NRAS were screened for mutations by melting curve
      analysis. Reverse transcription PCR and fluorescence in-situ hybridization were
      performed to confirm the array comparative genomic hybridization results.
      Pairwise comparisons revealed distinct genomic profiles between melanomas
      harboring different mutations. Primary melanomas with the BRAF mutation exhibited
      more frequent losses on 10q23-q26 and gains on chromosome 7 and 1q23-q25 compared
      with melanomas with the NRAS mutation. Loss on the 11q23-q25 sequence was found
      mainly in conjunction with the NRAS mutation. Primary melanomas without the BRAF
      or the NRAS mutation showed frequent alterations in chromosomes 17 and 4.
      Correlation analysis revealed chromosomal alterations that coexist more often in
      these tumor subgroups. To find classifiers for BRAF mutation, random forest
      analysis was used. Fifteen candidates emerged with 87% prediction accuracy.
      Signaling interactions between the EGF/MAPK-JAK pathways were observed to be
      extensively altered in melanomas with the BRAF mutation. We found marked
      differences in the genetic pattern of the BRAF and NRAS mutated melanoma
      subgroups that might suggest that these mutations contribute to malignant
      melanoma in conjunction with distinct cooperating oncogenic events.

PMID- 22456167
TI  - Effect of adenotonsillectomy on the use of respiratory medication.
AB  - OBJECTIVE: Recurrent tonsillitis and upper respiratory tract obstruction due to
      adenotonsillar hypertrophy are the most common indications for
      (adeno)tonsillectomy ((A)TE). Symptoms of upper respiratory tract infection and
      obstruction can, however, be attributed to lower airway pathology and thus
      treated with respiratory medication - this is non-antimicrobial medication used
      for lower respiratory diseases like bronchitis, bronchiolitis, asthma and
      episodic wheezing. The aim of this study is to investigate the effect of the
      current (A)TE practice in Belgium on the use of respiratory medication in
      subjects aged 0-15. METHODS: Retrospective data on 11.114 subjects aged 0-15
      years old who underwent (A)TE from January 1st 2002 until Sept 30th 2003 were
      retrieved from the database of the Christelijke Mutualiteit, the largest mutual
      health insurance society in Belgium. We compared the use of respiratory
      medication 12 months before and 12 months after (A)TE. RESULTS: Out of 11.114
      subjects, 4.654 received at least one prescription for respiratory medication in
      the year before and/or after (A)TE. In this subgroup, the median respiratory
      medication use reduced with 32% in the year after surgery. CONCLUSION: Compared
      with the year before surgery, the median use of respiratory medication in
      subjects aged 0-15 drastically reduces in the year after (A)TE. A possible reason
      for this reduction is that children with upper airway obstruction and infections
      are often wrongly diagnosed as having lower airway problems.

PMID- 22456168
TI  - Effect of tympanostomy tube surface on occlusion.
AB  - OBJECTIVE: Premature tympanostomy tube (TT) occlusion frequently leads to TT
      replacement surgery. TT surface preparations have been suggested as a means of
      reducing TT occlusion. The purpose of this study is to determine if commercial TT
      compositions or surface preparations impact the rate of TT occlusion using an in
      vitro model. METHODS: Commercial TTs composed of titanium, fluoroplastic, and
      silicone, as well as human serum albumin coated titanium, phosphorylcholine
      coated fluoroplastic, and polyvinylpyrrolidone coated silicone TTs, were tested
      for occlusion development in a previously validated in vitro model that simulates
      middle ear air and mucus flow. RESULTS: Time to occlusion was longer with all
      coated TTs relative to all uncoated TTs (p=0.038). Polyvinylpyrrolidone coated
      silicone TTs had the lowest rate of occlusion and improvement relative to
      silicone (36% vs. 70%). Time to occlusion was longer in all coated TTs, but
      individually, none reached statistical significance. CONCLUSION: TT composition
      and surface preparations do not dramatically impact the development of TT
      occlusion. All tested surface coatings seem to delay TT occlusion in this in
      vitro model. In vivo testing will be necessary to validate these findings.

PMID- 22456169
TI  - [Repeated liver resections in colorectal metastases].

PMID- 22456170
TI  - [Cardiac arrest in hospital].

PMID- 22456171
TI  - [Registries of in-hospital cardiac arrest are a challenge in daily clinical
      practice].
AB  - In-hospital cardiac arrest carries a poor prognosis. Registries of in-hospital
      cardiac arrest provide the opportunity to improve quality of care and conduct
      research of disease mechanisms and treatment. This paper describes the
      preliminary experience with systematic registration of in-hospital cardiac arrest
      at Aarhus University Hospital, Denmark. Data from 102 patients are presented and
      practical aspects and challenges of establishing a registry and implementing the
      collection of data in daily clinical practice are discussed.

PMID- 22456172
TI  - [Unclear effect of influenza vaccination in healthy adults].
AB  - At some Danish workplaces, healthy employees are offered an influenza
      vaccination, although vaccination has not been proven to have a protective effect
      on healthy adults. This article gives an overview of the effect of influenza
      vaccination on healthy adults based on the results from the Cochrane review
      "Vaccines for preventing influenza in healthy adults" and new studies in the
      field of interest. These studies show a limited effect on influenza, influenza
      like illness, lost workdays, physician visits and days of illness.

PMID- 22456173
TI  - [Diagnosis of multiple sclerosis--the 2010 revision of the McDonald criteria].
AB  - The 2010 revision of the McDonald diagnostic criteria for multiple sclerosis is
      reviewed. The diagnostic criteria have been simplified, which allows earlier
      diagnosis and treatment of multiple sclerosis.

PMID- 22456174
TI  - [Treatment of epithelian ovarian cancer should be followed by lymphadenectomy--a
      systematic review].
AB  - The role of lymphadenectomy in the treatment of epithelial ovarian cancer has
      been the object of controversy for years. The effect regarding stage and
      prognosis has been systematically reviewed through the existing literature.
      Lymphadenectomy gives a better clinical staging and is correlated with a better
      survival, but causes more surgical complications. It is advisable that all women
      with epithelial ovarian cancer have lymphadenectomy performed, thus ensuring a
      correct staging and thereby the optimal treatment.

PMID- 22456175
TI  - [Atrial myxom is a rare cause of peripheral embolus].
AB  - Two case stories of seemingly healthy individuals, a 45 year-old male and a 54
      year-old woman, with acute lower extremity ischemia caused by cardiac myxomas.
      Both patients had a lower extremity amputated and a removal of myxomas by
      surgery. In patients presenting with acute ischemia of the lower extremity
      surgeons need to consider this rare, but important diagnosis; especially in
      middle-aged, otherwise healthy patients. Performing an ultrasound sonography of
      the heart is the best way to make a diagnosis.

PMID- 22456176
TI  - [Spontaneous, bilateral fracture of the collum femoris by diabetic kidney
      insufficiency].
AB  - Spontaneous, bilateral, atraumatic pains from the hip is seldom regarded as a
      fracture. Often bilateral hip fracture is caused by a major degree of trauma or
      after a mechanical fall in elderly with bone disease. The treatment of patients
      with secondary osteoporosis such as renal osteodystrophy is an interdisciplinary
      task. Fracture of the collum femoris is also a relevant differential diagnosis in
      an uncharacteristic syndrome including abdominal pain, pain in the hips when
      moving, and in patients with severe diabetes.

PMID- 22456177
TI  - [Neglected non-melanoma skin cancer].
AB  - In Denmark the incidence of non-melanoma skin cancer (NMSC) has increased over
      the past 30 years, and it is presumed that the incidence of neglected NMSC will
      increase. Neglected NMSC is frequently seen in patients with psychosocial
      disabilities. If treatment is delayed consequences regarding treatment options
      and prognosis can be severe. We describe two cases of patients with psychosocial
      disabilities and neglected NMSC. In conclusion physicians, who treat patients
      with psychosocial disabilities and NMSCs, should be aware of the risk of neglect
      and ensure that treatment is complied.

PMID- 22456178
TI  - TRAIL-activated EGFR by Cbl-b-regulated EGFR redistribution in lipid rafts
      antagonises TRAIL-induced apoptosis in gastric cancer cells.
AB  - Most gastric cancer cells are resistant to tumour necrosis factor-related
      apoptosis-inducing ligand (TRAIL). Since TRAIL resistance is associated with
      lipid rafts, in which both death receptors and epidermal growth factor receptors
      (EGFR) are enriched, our aim is to identify how lipid raft-regulated receptor
      redistribution influences the sensitivity of TRAIL in gastric cancer cells. In
      TRAIL-resistant gastric cancer cells, TRAIL did not induce effective death
      inducing signalling complex (DISC) formation in lipid rafts, accompanied with
      EGFR translocation into lipid rafts, and activation of EGFR pathway. Knockdown of
      casitas B-lineage lymphoma-b (Cbl-b) enhanced TRAIL-induced apoptosis by
      promoting DISC formation in lipid rafts. However, knockdown of Cbl-b also
      enhanced EGFR translocation into lipid rafts and EGFR pathway activation induced
      by TRAIL. Either using inhibitors of EGFR or depletion of EGFR with small
      interfering RNA (siRNA) prevented EGFR pathway activation, and thus increased
      TRAIL-induced apoptosis, especially in Cbl-b knockdown clones. Taken together,
      TRAIL-induced EGFR activation through Cbl-b-regulated EGFR redistribution in
      lipid rafts antagonised TRAIL-induced apoptosis. The contribution of DISC
      formation and the inhibition of EGFR signal triggered in lipid rafts are both
      essential for increasing the sensitivity of gastric cancer cells to TRAIL.

PMID- 22456179
TI  - Effect of hospital volume on postoperative mortality and survival after
      oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009.
AB  - BACKGROUND: High hospital volume is associated with better outcomes after
      oesophagectomy and gastrectomy. In the Netherlands, a minimal volume standard of
      10 oesophagectomies per year was introduced in 2006. For gastrectomy, no minimal
      volume standard was set. Aims of this study were to describe changes in hospital
      volumes, mortality and survival and to explore if high hospital volume is
      associated with better outcomes after oesophagectomy and gastrectomy in the
      Netherlands. METHODS: From 1989 to 2009, 24,246 patients underwent oesophagectomy
      (N = 10,025) or gastrectomy (N = 14,221) in the Netherlands. Annual hospital
      volumes were defined as very low (1-5), low (6-10), medium (11-20), and high (>=
      21). Volume-outcome analyses were performed using Cox regression, adjusting for
      year of diagnosis, case-mix and the use of multi-modality treatment. RESULTS:
      From 1989 to 2009, the percentage of patients treated in high-volume hospitals
      increased for oesophagectomy (from 7% to 64%), but decreased for gastrectomy
      (from 8% to 5%). Six-month mortality (from 15% to 7%) and 3-year survival (from
      41% to 52%) improved after oesophagectomy, and to a lesser extent after
      gastrectomy (6-month mortality: 15%-10%, three-year survival: 55-58%). High
      hospital volume was associated with lower 6-month mortality (hazard ratio (HR)
      0.48, P<0.001) and longer 3-year survival (HR 0.77, P<0.001) after
      oesophagectomy, but not after gastrectomy. CONCLUSIONS: Oesophagectomy was
      effectively centralised in the Netherlands, improving mortality and survival.
      Gastrectomies were mainly performed in low volumes, and outcomes after
      gastrectomy improved to a lesser extent, indicating an urgent need for
      improvement in quality of surgery and perioperative care for gastric cancer in
      the Netherlands.

PMID- 22456180
TI  - Transient magnetic birefringence for determining magnetic nanoparticle diameters
      in dense, highly light scattering media.
AB  - The increasing use of biofunctionalized magnetic nanoparticles in biomedical
      applications calls for further development of characterization tools that allow
      for determining the interactions of the nanoparticles with the biological medium
      in situ. In cell-incubating conditions, for example, nanoparticles may aggregate
      and serum proteins adsorb on the particles, altering the nanoparticles'
      performance and their interaction with cell membranes. In this work we show that
      the aggregation of spherical magnetite nanoparticles can be detected with high
      sensitivity in dense, highly light scattering media by making use of magnetically
      induced birefringence. Moreover, the hydrodynamic particle diameter distribution
      of anisometric nanoparticle aggregates can be determined directly in these media
      by monitoring the relaxation time of the magnetically induced birefringence. As a
      proof of concept, we performed measurements on nanoparticles included in an
      agarose gel, which scatters light in a similar way as a more complex biological
      medium but where particle-matrix interactions are weak. Magnetite nanoparticles
      were separated by agarose gel electrophoresis and the hydrodynamic diameter
      distribution was determined in situ. For the different particle
      functionalizations and agarose concentrations tested, we could show that gel
      electrophoresis did not yield a complete separation of monomers and small
      aggregates, and that the electrophoretic mobility of the aggregates decreased
      linearly with the hydrodynamic diameter. Furthermore, the rotational particle
      diffusion was not clearly affected by nanoparticle-gel interactions. The
      possibility to detect nanoparticle aggregates and their hydrodynamic diameters in
      complex scattering media like cell tissue makes transient magnetic birefringence
      an interesting technique for biological applications.

PMID- 22456181
TI  - Platelets contribute to the pathogenesis of experimental autoimmune
      encephalomyelitis.
AB  - RATIONALE: Multiple sclerosis (MS) and its mouse model, experimental autoimmune
      encephalomyelitis (EAE), are inflammatory disorders of the central nervous system
      (CNS). The function of platelets in inflammatory and autoimmune pathologies is
      thus far poorly defined. OBJECTIVE: We addressed the role of platelets in
      mediating CNS inflammation in EAE. METHODS AND RESULTS: We found that platelets
      were present in human MS lesions as well as in the CNS of mice subjected to EAE
      but not in the CNS from control nondiseased mice. Platelet depletion at the
      effector-inflammatory phase of EAE in mice resulted in significantly ameliorated
      disease development and progression. EAE suppression on platelet depletion was
      associated with reduced recruitment of leukocytes to the inflamed CNS, as
      assessed by intravital microscopy, and with a blunted inflammatory response. The
      platelet-specific receptor glycoprotein Ibalpha (GPIbalpha) promotes both
      platelet adhesion and inflammatory actions of platelets and targeting of
      GPIbalpha attenuated EAE in mice. Moreover, targeting another platelet adhesion
      receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice.
      CONCLUSIONS: Platelets contribute to the pathogenesis of EAE by promoting CNS
      inflammation. Targeting platelets may therefore represent an important new
      therapeutic approach for MS treatment.

PMID- 22456182
TI  - Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase.
AB  - RATIONALE: The function of Nox4, a source of vascular H(2)O(2), is unknown. Other
      Nox proteins were identified as mediators of endothelial dysfunction. OBJECTIVE:
      We determined the function of Nox4 in situations of increased stress induced by
      ischemia or angiotensin II with global and tamoxifen-inducible Nox4(-/-) mice.
      METHODS AND RESULTS: Nox4 was highly expressed in the endothelium and contributed
      to H(2)O(2) formation. Nox4(-/-) mice exhibited attenuated angiogenesis (femoral
      artery ligation) and PEG-catalase treatment in control mice had a similar effect.
      Tube formation in cultured Nox4(-/-) lung endothelial cells (LECs) was attenuated
      and restored by low concentrations of H(2)O(2,) whereas PEG-catalase attenuated
      tube formation in control LECs. Angiotensin II infusion was used as a model of
      oxidative stress. Compared to wild-type, aortas from inducible Nox4-deficient
      animals had development of increased inflammation, media hypertrophy, and
      endothelial dysfunction. Mechanistically, loss of Nox4 resulted in reduction of
      endothelial nitric oxide synthase expression, nitric oxide production, and heme
      oxygenase-1 (HO-1) expression, which was associated with apoptosis and
      inflammatory activation. HO-1 expression is controlled by Nrf-2. Accordingly,
      Nox4-deficient LECs exhibited reduced Nrf-2 protein level and deletion of Nox4
      reduced Nrf-2 reporter gene activity. In vivo treatment with hemin, an inducer of
      HO-1, blocked the vascular hypertrophy induced by Nox4 deletion in the
      angiotensin II infusion model and carbon monoxide, the product of HO-1, blocked
      the Nox4-deletion-induced apoptosis in LECs. CONCLUSION: Endogenous Nox4 protects
      the vasculature during ischemic or inflammatory stress. Different from Nox1 and
      Nox2, this particular NADPH oxidase therefore may have a protective vascular
      function.

PMID- 22456183
TI  - Substrate- and isoform-specific proteome stability in normal and stressed cardiac
      mitochondria.
AB  - RATIONALE: Mitochondrial protein homeostasis is an essential component of the
      functions and oxidative stress responses of the heart. OBJECTIVE: To determine
      the specificity and efficiency of proteome turnover of the cardiac mitochondria
      by endogenous and exogenous proteolytic mechanisms. METHODS AND RESULTS:
      Proteolytic degradation of the murine cardiac mitochondria was assessed by 2
      dimensional differential gel electrophoresis and liquid chromatography-tandem
      mass spectrometry. Mitochondrial proteases demonstrated a substrate preference
      for basic protein variants, which indicates a possible recognition mechanism
      based on protein modifications. Endogenous mitochondrial proteases and the
      cytosolic 20S proteasome exhibited different substrate specificities.
      CONCLUSIONS: The cardiac mitochondrial proteome contains low amounts of proteases
      and is remarkably stable in isolation. Oxidative damage lowers the proteolytic
      capacity of cardiac mitochondria and reduces substrate availability for
      mitochondrial proteases. The 20S proteasome preferentially degrades specific
      substrates in the mitochondria and may contribute to cardiac mitochondrial
      proteostasis.

PMID- 22456184
TI  - AMP-activated protein kinase phosphorylates cardiac troponin I and alters
      contractility of murine ventricular myocytes.
AB  - RATIONALE: AMP-activated protein kinase (AMPK) is an important regulator of
      energy balance and signaling in the heart. Mutations affecting the regulatory
      gamma2 subunit have been shown to cause an essentially cardiac-restricted
      phenotype of hypertrophy and conduction disease, suggesting a specific role for
      this subunit in the heart. OBJECTIVE: The gamma isoforms are highly conserved at
      their C-termini but have unique N-terminal sequences, and we hypothesized that
      the N-terminus of gamma2 may be involved in conferring substrate specificity or
      in determining intracellular localization. METHODS AND RESULTS: A yeast 2-hybrid
      screen of a human heart cDNA library using the N-terminal 273 residues of gamma2
      as bait identified cardiac troponin I (cTnI) as a putative interactor. In vitro
      studies showed that cTnI is a good AMPK substrate and that Ser150 is the
      principal residue phosphorylated. Furthermore, on AMPK activation during
      ischemia, Ser150 is phosphorylated in whole hearts. Using phosphomimics,
      measurements of actomyosin ATPase in vitro and force generation in demembraneated
      trabeculae showed that modification at Ser150 resulted in increased Ca(2+)
      sensitivity of contractile regulation. Treatment of cardiomyocytes with the AMPK
      activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) resulted in
      increased myocyte contractility without changing the amplitude of Ca(2+)
      transient and prolonged relaxation despite shortening the time constant of Ca(2+)
      transient decay (tau). Compound C prevented the effect of AICAR on myocyte
      function. These results suggest that AMPK activation increases myocyte
      contraction and prolongs relaxation by increasing myofilament Ca(2+) sensitivity.
      CONCLUSIONS: We conclude that cTnI phosphorylation by AMPK may represent a novel
      mechanism of regulation of cardiac function.

PMID- 22456185
TI  - Blocking the rise of intracellular calcium inhibits the growth of cells cultured
      in different concentrations of magnesium.
AB  - Divalent cations, especially calcium and magnesium, have been shown to play an
      important regulatory role in endothelial and immune cells. To learn more about
      the interaction of these two metals in the regulation of cell growth, we altered
      the calcium/magnesium ratio by culturing human endothelial cells, macrophages,
      and T lymphocytes in media containing different concentrations of magnesium. We
      observed that the growth of the three cell types was retarded in low
      extracellular magnesium, and this retardation is particularly evident in highly
      proliferating cells. High concentrations of magnesium does not exert any effect
      on cell growth. When (i) calcium influx was blocked by adding the calcium
      antagonist verapamil, and (ii) calcium release from intracellular stores was
      inhibited by exposure to TMB-8, the growth of endothelial cells, macrophages, and
      T lymphocytes was inhibited. In particular, the release of calcium from
      intracellular stores seems to be more important than its influx in sustaining
      cell proliferation. Our results indicate that calcium plays a crucial role in
      mediating cell proliferation independently from the extracellular concentrations
      of magnesium.

PMID- 22456186
TI  - Endoscopic minimally invasive neurosurgery: emerging techniques and expanding
      role through an extensive review of the literature and our own experience - part
      I: intraendoscopic neurosurgery.
AB  - BACKGROUND/AIMS: Minimally invasive neurosurgery is a growing field, more so in
      recent decades. The modernization of tools, especially the endoscope, has allowed
      for critical improvements and crucial advancements in minimally invasive
      neurosurgery. The current classification scheme for endoscopic procedures needs
      to be updated to reflect these advancements. METHODS: Although the field of
      neuroendoscopy is continually evolving, the terminologies utilized to describe
      endoscopic procedures reflect and favor its use as mostly an assisting device
      complementing the microscope. Even though the classification was adequate for its
      time, it has become inexact and therefore confusing. We therefore propose a new
      classification scheme that encompasses the growing independence of endoscopic
      minimally invasive neurosurgery (EMIN) as well as the changing landscape within
      EMIN procedures. RESULTS: We have classified our EMIN procedures, since 2002, as
      either 'intraendoscopic' (IEN) or 'extraendoscopic' (XEN) in relation to the
      endoscope's axis. Exemplary cases of IEN and a review of the literature are
      presented as well. CONCLUSION: Our proposed classification scheme for solely
      endoscopic procedures is presented. The role of the endoscope as an independent
      tool is clarified.

PMID- 22456187
TI  - Assessing the quality of research needs to go beyond scoring: commentary on Crowe
      and Sheppard (2011).

PMID- 22456188
TI  - Should I stay or should I go? Ephs and ephrins in neuronal migration.
AB  - In neuroscience, Ephs and ephrins are perhaps best known for their role in axon
      guidance. It was first shown in the visual system that graded expression of these
      proteins is instrumental in providing molecular coordinates that define
      topographic maps, particularly in the visual system, but also in the auditory,
      vomeronasal and somatosensory systems as well as in the hippocampus, cerebellum
      and other structures. Perhaps unsurprisingly, the role of these proteins in
      regulating cell-cell interactions also has an impact on cell mobility, with
      evidence that Eph-ephrin interactions segregate cell populations based on contact
      mediated attraction or repulsion. Consistent with these studies, evidence has
      accumulated that Ephs and ephrins play important roles in the migration of
      specific cell populations in the developing and adult brain. This review focusses
      on two examples of neuronal migration that require Eph/ephrin signalling - radial
      and tangential migration of neurons in cortical development and the migration of
      newly generated neurons along the rostral migratory stream to the olfactory bulb
      in the adult brain. We discuss the challenge involved in understanding how cells
      determine whether they respond to signals by migration or axon guidance.

PMID- 22456190
TI  - Ghrelin prevents neuronal apoptosis and cognitive impairments in sepsis
      associated encephalopathy: Retraction.

PMID- 22456191
TI  - Current world literature.

PMID- 22456193
TI  - Prevalence of autism spectrum disorders--Autism and Developmental Disabilities
      Monitoring Network, 14 sites, United States, 2008.
AB  - PROBLEM/CONDITION: Autism spectrum disorders (ASDs) are a group of developmental
      disabilities characterized by impairments in social interaction and communication
      and by restricted, repetitive, and stereotyped patterns of behavior. Symptoms
      typically are apparent before age 3 years. The complex nature of these disorders,
      coupled with a lack of biologic markers for diagnosis and changes in clinical
      definitions over time, creates challenges in monitoring the prevalence of ASDs.
      Accurate reporting of data is essential to understand the prevalence of ASDs in
      the population and can help direct research. PERIOD COVERED: 2008. DESCRIPTION OF
      SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an
      active surveillance system that estimates the prevalence of ASDs and describes
      other characteristics among children aged 8 years whose parents or guardians
      reside within 14 ADDM sites in the United States. ADDM does not rely on
      professional or family reporting of an existing ASD diagnosis or classification
      to ascertain case status. Instead, information is obtained from children's
      evaluation records to determine the presence of ASD symptoms at any time from
      birth through the end of the year when the child reaches age 8 years. ADDM
      focuses on children aged 8 years because a baseline study conducted by CDC
      demonstrated that this is the age of identified peak prevalence. A child is
      included as meeting the surveillance case definition for an ASD if he or she
      displays behaviors (as described on a comprehensive evaluation completed by a
      qualified professional) consistent with the American Psychiatric Association's
      Diagnostic and Statistical Manual-IV, Text Revision (DSM-IV-TR) diagnostic
      criteria for any of the following conditions: Autistic Disorder; Pervasive
      Developmental Disorder-Not Otherwise Specified (PDD-NOS, including Atypical
      Autism); or Asperger Disorder. The first phase of the ADDM methodology involves
      screening and abstraction of comprehensive evaluations completed by professional
      providers at multiple data sources in the community. Multiple data sources are
      included, ranging from general pediatric health clinics to specialized programs
      for children with developmental disabilities. In addition, many ADDM sites also
      review and abstract records of children receiving special education services in
      public schools. In the second phase of the study, all abstracted evaluations are
      reviewed by trained clinicians to determine ASD case status. Because the case
      definition and surveillance methods have remained consistent across all ADDM
      surveillance years to date, comparisons to results for earlier surveillance years
      can be made. This report provides updated ASD prevalence estimates from the 2008
      surveillance year, representing 14 ADDM areas in the United States. In addition
      to prevalence estimates, characteristics of the population of children with ASDs
      are described, as well as detailed comparisons of the 2008 surveillance year
      findings with those for the 2002 and 2006 surveillance years. RESULTS: For 2008,
      the overall estimated prevalence of ASDs among the 14 ADDM sites was 11.3 per
      1,000 (one in 88) children aged 8 years who were living in these communities
      during 2008. Overall ASD prevalence estimates varied widely across all sites
      (range: 4.8-21.2 per 1,000 children aged 8 years). ASD prevalence estimates also
      varied widely by sex and by racial/ethnic group. Approximately one in 54 boys and
      one in 252 girls living in the ADDM Network communities were identified as having
      ASDs. Comparison of 2008 findings with those for earlier surveillance years
      indicated an increase in estimated ASD prevalence of 23% when the 2008 data were
      compared with the data for 2006 (from 9.0 per 1,000 children aged 8 years in 2006
      to 11.0 in 2008 for the 11 sites that provided data for both surveillance years)
      and an estimated increase of 78% when the 2008 data were compared with the data
      for 2002 (from 6.4 per 1,000 children aged 8 years in 2002 to 11.4 in 2008 for
      the 13 sites that provided data for both surveillance years). Because the ADDM
      Network sites do not make up a nationally representative sample, these combined
      prevalence estimates should not be generalized to the United States as a whole.
      INTERPRETATION: These data confirm that the estimated prevalence of ASDs
      identified in the ADDM network surveillance populations continues to increase.
      The extent to which these increases reflect better case ascertainment as a result
      of increases in awareness and access to services or true increases in prevalence
      of ASD symptoms is not known. ASDs continue to be an important public health
      concern in the United States, underscoring the need for continued resources to
      identify potential risk factors and to provide essential supports for persons
      with ASDs and their families. PUBLIC HEALTH ACTION: Given substantial increases
      in ASD prevalence estimates over a relatively short period, overall and within
      various subgroups of the population, continued monitoring is needed to quantify
      and understand these patterns. With 5 biennial surveillance years completed in
      the past decade, the ADDM Network continues to monitor prevalence and
      characteristics of ASDs and other developmental disabilities for the 2010
      surveillance year. Further work is needed to evaluate multiple factors
      contributing to increases in estimated ASD prevalence over time. ADDM Network
      investigators continue to explore these factors, with a focus on understanding
      disparities in the identification of ASDs among certain subgroups and on how
      these disparities have contributed to changes in the estimated prevalence of
      ASDs. CDC is partnering with other federal and private partners in a coordinated
      response to identify risk factors for ASDs and to meet the needs of persons with
      ASDs and their families.

PMID- 22456194
TI  - Differential profiles of crack users in respondent-driven and institutional
      samples: a three-site comparison.
AB  - BACKGROUND/AIM: Respondent-driven sampling (RDS) is increasingly applied in
      social epidemiological surveys among 'hidden populations' of hard drug users. The
      objective of the present study was to assess whether the profile of frequent
      crack users recruited through RDS differed from those surveyed in two random
      institutional samples, i.e. low-threshold opiate substitution treatment (ST) and
      user rooms (URs). METHODS: A total of 1,039 crack users (mean age 45.1 +/- 9.1
      years; 81.5% males; 49.5% non-Western ethnicity) were interviewed in three Dutch
      cities, using each sampling strategy in each city. Characteristics of respondents
      in the three samples (per city and aggregated) were compared. RESULTS: Crack
      users in the RDS sample were more likely to be younger and less likely to be
      poorly educated, have a long crack-using career (>=10 years), use opiates and
      attend ST than those in both of the other samples. The RDS and UR samples showed
      the most differences, with more female and Western crack users in the RDS group,
      and UR participants were more likely to have been arrested and to have entered
      inpatient drug treatment in the last year. CONCLUSION: RDS resulted in a
      different profile of crack users. It is a valuable methodology to achieve a more
      diverse representation of crack-using populations than institutional random
      samples.

PMID- 22456195
TI  - Pharmacokinetic, distribution, metabolism, and excretion of (Z)-2-amino-1,5
      dihydro-1-methyl-5-[4-(mesyl)benzylidene]-4H-imidazol-4-one mesilate (ZLJ-601) in
      Sprague-Dawley rats.
AB  - (Z)-2-amino-1,5-dihydro-1-methyl-5-[4-(mesyl)benzylidene]-4H-imidazol-4-one
      mesilate (ZLJ-601) is an imidazolone COX/5-LOX inhibitor, which has excellent
      anti-inflammatory activity with an improved gastrointestinal safety profile. The
      purpose of this study was to evaluate the in vivo absorption, distribution,
      metabolism, and excretion of ZLJ-601 in Sprague-Dawley rats. After intravenous or
      intragastric administration to rats, the concentration of ZLJ-601 in plasma,
      bile, urine, feces and various types of tissues was detected by LC-MS. We also
      conducted the identification of metabolites using tandem mass spectrometry. After
      the intravenous administration, the t(1/2) ranged from 38.71 to 42.62 min and the
      AUC increased in a dose-proportional manner. After oral dosing, the plasma level
      of ZLJ-601 peaked at 28.33 min, having a C(max) value of 0.26 mg/l, and the
      bioavailability was only 4.92%. The highest tissue concentration of ZLJ-601 was
      observed in lung and kidney, but it was not found in brain. The majority of
      unchanged ZLJ-601 was excreted in urine (~35.87%) within 36 h. Two main
      metabolites are the hydroxylation product and the glucuronide conjugate of the
      hydroxylation product.

PMID- 22456197
TI  - TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated
      and castration-resistant growth of prostate cancer.
AB  - Despite the existence of effective antiandrogen therapy for prostate cancer, the
      disease often progresses to castration-resistant states. Elucidation of the
      molecular mechanisms underlying the resistance for androgen deprivation in terms
      of the androgen receptor (AR)-regulated pathways is a requisite to manage
      castration-resistant prostate cancer (CRPC). Using a ChIP-cloning strategy, we
      identified functional AR binding sites (ARBS) in the genome of prostate cancer
      cells. We discovered that a centrosome- and microtubule-interacting gene,
      transforming acidic coiled-coil protein 2 (TACC2), is a novel androgen-regulated
      gene. We identified a functional AR-binding site (ARBS) including two canonical
      androgen response elements in the vicinity of TACC2 gene, in which activated
      hallmarks of histone modification were observed. Androgen-dependent TACC2
      induction is regulated by AR, as confirmed by AR knockdown or its pharmacological
      inhibitor bicalutamide. Using long-term androgen-deprived cells as cellular
      models of CRPC, we demonstrated that TACC2 is highly expressed and contributes to
      hormone-refractory proliferation, as small interfering RNA-mediated knockdown of
      TACC2 reduced cell growth and cell cycle progression. By contrast, in TACC2
      overexpressing cells, an acceleration of the cell cycle was observed. In vivo
      tumor formation study of prostate cancer in castrated immunocompromised mice
      revealed that TACC2 is a tumor-promoting factor. Notably, the clinical
      significance of TACC2 was demonstrated by a correlation between high TACC2
      expression and poor survival rates. Taken together with the critical roles of
      TACC2 in the cell cycle and the biology of prostate cancer, we infer that the
      molecule is a potential therapeutic target in CRPC as well as hormone-sensitive
      prostate cancer.

PMID- 22456196
TI  - RhoA as a mediator of clinically relevant androgen action in prostate cancer
      cells.
AB  - Recently, we have identified serum response factor (SRF) as a mediator of
      clinically relevant androgen receptor (AR) action in prostate cancer (PCa). Genes
      that rely on SRF for androgen responsiveness represent a small fraction of
      androgen-regulated genes, but distinguish benign from malignant prostate,
      correlate with aggressive disease, and are associated with biochemical
      recurrence. Thus, understanding the mechanism(s) by which SRF conveys androgen
      regulation to its target genes may provide novel opportunities to target
      clinically relevant androgen signaling. Here, we show that the small GTPase ras
      homolog family member A (RhoA) mediates androgen-responsiveness of more than half
      of SRF target genes. Interference with expression of RhoA, activity of the RhoA
      effector Rho-associated coiled-coil containing protein kinase 1 (ROCK), and actin
      polymerization necessary for nuclear translocation of the SRF cofactor
      megakaryocytic acute leukemia (MAL) prevented full androgen regulation of SRF
      target genes. Androgen treatment induced RhoA activation, increased the nuclear
      content of MAL, and led to MAL recruitment to the promoter of the SRF target gene
      FHL2. In clinical specimens RhoA expression was higher in PCa cells than benign
      prostate cells, and elevated RhoA expression levels were associated with
      aggressive disease features and decreased disease-free survival after radical
      prostatectomy. Overexpression of RhoA markedly increased the androgen
      responsiveness of select SRF target genes, in a manner that depends on its GTPase
      activity. The use of isogenic cell lines and a xenograft model that mimics the
      transition from androgen-stimulated to castration-recurrent PCa indicated that
      RhoA levels are not altered during disease progression, suggesting that RhoA
      expression levels in the primary tumor determine disease aggressiveness. Androgen
      responsiveness of SRF target genes in castration-recurrent PCa cells continued to
      rely on AR, RhoA, SRF, and MAL and the presence of intact SRF binding sites.
      Silencing of RhoA, use of Rho-associated coiled-coil containing protein kinase 1
      inhibitors, or an inhibitor of SRF-MAL interaction attenuated (androgen
      regulated) cell viability and blunted PCa cell migration. Taken together, these
      studies demonstrate that the RhoA signaling axis mediates clinically relevant AR
      action in PCa.

PMID- 22456198
TI  - Adenocarcinoma arising from a gastric duplication cyst.
AB  - Malignant transformation in a gastric duplication cyst (GDC) is extremely rare,
      with only eight reported cases to date. An additional case of an adenocarcinoma
      arising from a GDC in a 25-year-old male is reported here. Ultrasonography and
      computed tomography (CT) scans detected a well-defined cyst arising from the
      greater curvature of the stomach. The patient was submitted to en-bloc resection
      of the mass with total gastrectomy and regional lymphadenectomy. At the time of
      laparotomy, the unilocular cyst was full of a thick substance and had no
      association with the gastric lumen. Microscopic examination revealed that the
      cystic mass had a well-formed cyst wall with an inner mucosal lining, submucosal
      layer, muscularis propria, and outer serosal layer. The inner cyst was lined by
      gastric mucosa. A mediated differentiated adenocarcinoma was found in the
      duplication cyst, which had invaded the serosa of the cyst wall and the gastric
      muscular wall. To our knowledge, this is the youngest and only asymptomatic
      patient in whom neoplastic GDC changes have been reported.

PMID- 22456199
TI  - Endoscopic minimally invasive neurosurgery: emerging techniques and expanding
      role through an extensive review of the literature and our own experience - part
      II: extraendoscopic neurosurgery.
AB  - BACKGROUND/AIMS: The field of minimally invasive neurosurgery has grown
      dramatically especially in the last decades. This has been possible, in the most
      part, due to the advancements in technology especially in tools such as the
      endoscope. The contemporary classification scheme for endoscopic procedures needs
      to advance as well. METHODS: The present classification scheme for
      neuroendoscopic procedures has become confusing because it mainly describes the
      use of the endoscope as an assisting device to the microscope. The authors
      propose an update to the current classification that reflects the independence of
      the endoscope as a tool in minimally invasive neurosurgery. RESULTS: The proposed
      classification groups the procedures as 'intraendoscopic' neurosurgery or
      'extraendoscopic' neurosurgery (XEN) in relation to the 'axis' of the endoscope.
      A review of the literature for the XEN group together with exemplary cases is
      presented. CONCLUSION: We presented our proposed classification for the endoscope
      only surgical procedures. The XEN group is expanded in this article.

PMID- 22456200
TI  - Surface functionalization for tailoring the aggregation and magnetic behaviour of
      silica-coated iron oxide nanostructures.
AB  - We report here a detailed structural and magnetic study of different silica
      nanocapsules containing uniform and highly crystalline maghemite nanoparticles.
      The magnetic phase consists of 5 nm triethylene glycol (TREG)- or
      dimercaptosuccinic acid (DMSA)-coated maghemite particles. TREG-coated
      nanoparticles were synthesized by thermal decomposition. In a second step, TREG
      ligands were exchanged by DMSA. After the ligand exchange, the zeta potential of
      the particles changed from -10 to -40 mV, whereas the hydrodynamic size remained
      constant at around 15 nm. Particles coated by TREG and DMSA were encapsulated in
      silica following a sol-gel procedure. The encapsulation of TREG-coated
      nanoparticles led to large magnetic aggregates, which were embedded in coalesced
      silica structures. However, DMSA-coated nanoparticles led to small magnetic
      clusters inserted in silica spheres of around 100 nm. The final nanostructures
      can be described as the result of several competing factors at play. Magnetic
      measurements indicate that in the TREG-coated nanoparticles the interparticle
      magnetic interaction scenario has not dramatically changed after the silica
      encapsulation, whereas in the DMSA-coated nanoparticles, the magnetic
      interactions were screened due to the function of the silica template. Moreover,
      the analysis of the AC susceptibility suggests that our systems essentially
      behave as cluster spin glass systems.

PMID- 22456201
TI  - Eruptive vellus hair cysts: report of a new case with immunohistochemical study
      and literature review.
AB  - Eruptive vellus hair cysts (EVHC) are rather uncommon lesions, of which 222 cases
      have been published in the literature. Their etiopathogenesis is poorly known. We
      report herein a new typical case of EVHC that was studied immunohistochemically.
      A 15-year-old male presented with a 4-year history of progressively developing
      small brown-gray papules on the trunk and extremities. Microscopically the
      lesions consisted of small epidermoid cysts containing vellus hairs.
      Immunohistochemically, the lesions expressed keratin 1/10, calretinin and p63 but
      no epithelial membrane antigen, filaggrin or androgen receptors. A review of the
      relevant literature shows that EVHC may be inherited or acquired and may be
      associated to other genodermatoses, namely sebocystomatosis. They could be due to
      hamartomatous follicular growth, to a trouble in infundibular keratinization
      leading to vellus hair follicle occlusion, or represent an example of acquired
      hamartoma. Although benign, this condition is difficult to treat.

PMID- 22456202
TI  - Still haunted by an error.

PMID- 22456207
TI  - Instituting Quiet Hour improves patient satisfaction.

PMID- 22456208
TI  - A voice for Hope.

PMID- 22456211
TI  - Congratulations to the Nursing2012 nurse of the year.

PMID- 22456213
TI  - New hope for those with hereditary angioedema.

PMID- 22456214
TI  - Pump it up with an LVAD left ventricular assist device.

PMID- 22456215
TI  - Patient education series. Mitral valve prolapse.

PMID- 22456216
TI  - An inside look at correctional health nursing.

PMID- 22456217
TI  - Transporting critically ill patients.

PMID- 22456218
TI  - Fluffing the pillows.

PMID- 22456219
TI  - "Swoop and scoop": pediatric emergencies in an adult hospital.

PMID- 22456220
TI  - Systemic heparinization after subarachnoid hemorrhage.

PMID- 22456221
TI  - NDM-1: the newest superbug?

PMID- 22456223
TI  - Urinary tract infection in older adults.

PMID- 22456224
TI  - Vascularization in tissue engineering: angiogenesis versus inosculation.
AB  - BACKGROUND/PURPOSE: The key challenge in tissue engineering is the establishment
      of an efficient vascularization for tissue constructs guaranteeing long-term
      survival and function. Vascularization may be achieved by the stimulation of
      angiogenesis or the inosculation of preformed microvascular networks within the
      implants to the host microvasculature. The present review provides an overview of
      these two concepts applied in tissue engineering. METHODS: A literature search
      was performed in PubMed for publications focusing on vascularization,
      angiogenesis and inosculation in tissue engineering. RESULTS: Several strategies
      have been proposed to stimulate the ingrowth of new blood vessels into tissue
      constructs. These include the modification of the chemical composition and
      architecture of scaffolds, their bioactivation by incorporation of growth factor
      delivery systems or by cell seeding as well as the stimulation of stem cell
      recruitment. However, because angiogenesis is a time-consuming process, all of
      these approaches cannot prevent ischemic cell death within larger 3-dimensional
      tissue constructs during the initial phase after implantation. To overcome this
      problem, in vitro or in situ prevascularization has emerged as a novel concept in
      tissue engineering. This bears the advantage that preformed microvascular
      networks within tissue constructs simply have to inosculate with the host
      microvasculature at the implantation site to get completely blood-perfused within
      a short period of time. CONCLUSIONS: During the last years, considerable progress
      has been made in the development of promising vascularization strategies in
      tissue engineering. Particularly the inosculation of preformed microvascular
      networks has the great potential to markedly improve the survival of tissue
      constructs after implantation. The optimization of this vascularization strategy
      may pave the way for a broad clinical use of tissue engineering applications in
      the future.

PMID- 22456225
TI  - Association of heart failure hospitalizations with combined electrocardiography
      and echocardiography criteria for left ventricular hypertrophy.
AB  - BACKGROUND: The value of performing echocardiography in hypertensive patients
      with electrocardiographic left ventricular hypertrophy (LVH) is uncertain.
      METHODS: Baseline echo- and electrocardiographic data and cardiovascular events
      over 4.8 years study treatment were assessed in 922 hypertensive patients in the
      Losartan Intervention For Endpoint reduction in hypertension echocardiography
      substudy. Patients were grouped according to presence of LVH on both
      electrocardiogram (ECG) and echocardiogram (n = 515), only on ECG (n = 172), only
      on echocardiogram (n = 135), or on none tests (n = 100). LVH was diagnosed by
      Sokolow Lyon and Cornell product criteria by electrocardiography and as LV mass
      index >116 g/m(2) in men and >104 g/m(2) in women by echocardiography. RESULTS:
      Patients with LVH on both tests were older, had higher systolic blood pressure
      and LV mass, lower LV systolic function, and included more patients with aortic
      regurgitation, albuminuria, and history of ischemic heart disease (all P < 0.05).
      Incidence of combined myocardial infarction, stroke, or cardiovascular death did
      not differ between groups. Incidence of hospitalization for heart failure was 5.3
      and 2.6 times higher in patients with LVH on both tests compared to patients with
      LVH on ECG or echocardiogram only (P < 0.01). In Cox regression, LVH on both
      tests predicted hospitalization for heart failure (hazard ratio 4.29 (95%
      confidence interval 1.26-14.65), P = 0.020) independent of other covariates
      including study treatment allocation and history of ischemic heart disease.
      CONCLUSIONS: Our results suggest that combining LVH assessment on a single ECG
      and echocardiogram provides a simple tool for additional heart failure risk
      stratification in asymptomatic high-risk hypertensive patients.

PMID- 22456227
TI  - Na+-dependent and Na+-independent mechanisms for inorganic phosphate uptake in
      Trypanosoma rangeli.
AB  - BACKGROUND: Trypanosoma rangeli is dependent on the presence of exogenous
      orthophosphate (Pi) for maximal growth and ecto-phosphatase activity is
      responsible for Pi supply under low Pi. Here we investigated the mechanisms of Pi
      uptake. METHODS: We investigated the kinetics of 32Pi transport, its Na+ and H+
      dependence, its correlation with the Na+-ATPase and H+-ATPase, and gene
      expression of the Na+:Pi cotransporter and Na+-ATPase. RESULTS: T. rangeli grown
      under limiting Pi transports this anion to the cytosol in the absence and
      presence of Na+, suggesting that influx is mediated by both Na+-independent and
      Na+-dependent transporters. Cloning studies demonstrated that this parasite
      expresses a Pi transporter not previously studied in trypanosomatids. The H+
      ionophore, carbonylcyanide-p-trifluoromethoxyphenylhydrazone, decreased both
      components of 32Pi influx by 80-95%. The H+-ATPase inhibitor, bafilomycin A1,
      inhibited the Na+-independent mechanism. Furosemide, an inhibitor of ouabain
      insensitive Na+-ATPase, decreased both uptake mechanisms of 32Pi to the same
      extent, whereas ouabain had no effect, indicating that the former is the pump
      responsible for inwardly directed Na+ and the electric gradients required by the
      transporters. Parasite growth in high Pi had a lower Pi influx than that found in
      those grown in low Pi, without alteration in TrPho89 expression, showing that
      turnover of the transporters is stimulated by Pi starvation. CONCLUSIONS: Two
      modes of Pi transport, one coupled to Na+-ATPase and other coupled to H+-ATPase
      seem to be responsible for Pi acquisition during development of T. rangeli.
      GENERAL SIGNIFICANCE: This study provides the first description of the mechanism
      of Pi transport across the plasma membrane of trypanosomatids.

PMID- 22456228
TI  - Intracellular free calcium content plays a role in low magnesium-induced
      increases in prostacyclin production.
AB  - In a previous study, we found that magnesium deficiency stimulated prostacyclin
      production and suggested that this stimulation resulted from an enhanced Ca2+
      influx induced by magnesium deficiency. In this study, we further examined
      prostacyclin generation in cultured human umbilical vein endothelial cells after
      intracellular free calcium content ([Ca2+]i) was altered by addition of
      diltiazem, nifedipine, verapamil, sodium cyanide (NaCN), ruthenium red or
      quinidine to a low magnesium medium. The results showed that diltiazem,
      nifedipine, verapamil and ruthenium red inhibited 45Ca2+ influx, and NaCN and
      quinidine had no effect on 45Ca2+ influx. However, all of these compounds
      decreased [Ca2+]i, [3H]arachidonic acid release and prostacyclin production. The
      reduced [3H]arachidonic acid content in cellular phospholipids caused by low
      magnesium treatment was not altered by the added compounds. We suggested that
      arachidonic acid release and prostacyclin production was calcium-dependent in
      cultured endothelial cells.

PMID- 22456226
TI  - Anorexigenic and orexigenic hormone modulation of mammalian target of rapamycin
      complex 1 activity and the regulation of hypothalamic agouti-related protein mRNA
      expression.
AB  - Activation of mammalian target of rapamycin 1 (mTORC1) by nutrients, insulin and
      leptin leads to appetite suppression (anorexia). Contrastingly, increased AMP
      activated protein kinase (AMPK) activity by ghrelin promotes appetite (orexia).
      However, the interplay between these mechanisms remains poorly defined. The
      relationship between the anorexigenic hormones, insulin and leptin, and the
      orexigenic hormone, ghrelin, on mTORC1 signalling was examined using S6 kinase
      phosphorylation as a marker for changes in mTORC1 activity in mouse hypothalamic
      GT1-7 cells. Additionally, the contribution of AMPK and mTORC1 signalling in
      relation to insulin-, leptin- and ghrelin-driven alterations to mouse
      hypothalamic agouti-related protein (AgRP) mRNA levels was examined. Insulin and
      leptin increase mTORC1 activity in a phosphoinositide-3-kinase (PI3K)- and
      protein kinase B (PKB)-dependent manner, compared to vehicle controls, whereas
      increasing AMPK activity inhibits mTORC1 activity and blocks the actions of the
      anorexigenic hormones. Ghrelin mediates an AMPK-dependent decrease in mTORC1
      activity and increases hypothalamic AgRP mRNA levels, the latter effect being
      prevented by insulin in an mTORC1-dependent manner. In conclusion, mTORC1 acts as
      an integration node in hypothalamic neurons for hormone-derived PI3K and AMPK
      signalling and mediates at least part of the assimilated output of anorexigenic
      and orexigenic hormone actions in the hypothalamus.

PMID- 22456229
TI  - Oligosaccharide/silicon-containing block copolymers with 5 nm features for
      lithographic applications.
AB  - Block copolymers demonstrate potential for use in next-generation lithography due
      to their ability to self-assemble into well-ordered periodic arrays on the 3-100
      nm length scale. The successful lithographic application of block copolymers
      relies on three critical conditions being met: high Flory-Huggins interaction
      parameters (chi), which enable formation of <10 nm features, etch selectivity
      between blocks for facile pattern transfer, and thin film self-assembly control.
      The present paper describes the synthesis and self-assembly of block copolymers
      composed of naturally derived oligosaccharides coupled to a silicon-containing
      polystyrene derivative synthesized by activators regenerated by electron transfer
      atom transfer radical polymerization. The block copolymers have a large chi and a
      low degree of polymerization (N) enabling formation of 5 nm feature diameters,
      incorporate silicon in one block for oxygen reactive ion etch contrast, and
      exhibit bulk and thin film self-assembly of hexagonally packed cylinders
      facilitated by a combination of spin coating and solvent annealing techniques. As
      observed by small angle X-ray scattering and atomic force microscopy, these
      materials exhibit some of the smallest block copolymer features in the bulk and
      in thin films reported to date.

PMID- 22456231
TI  - Novel intrapleural therapies for malignant diseases.
AB  - Pleural malignancies, either primary or metastatic, are common and problematic
      clinical issues in thoracic oncology and pulmonary medicine. Malignant pleural
      mesothelioma and metastatic pleural effusions often present late in the course of
      a disease and have a dramatic impact on the patient's quality of life and
      survival. Novel approaches to manage mesothelioma and malignant pleural effusions
      are desperately needed and the pleural space provides a unique platform as an
      easily accessible body cavity for developing and assessing these treatments and
      their responses. In this review, we discuss the unique intrapleural
      chemotherapeutic, immunotherapeutic and genetic treatments that have been
      investigated, as well as those under current clinical development. While
      responses have been demonstrated to variable degrees with all these approaches,
      an integrated multimodality approach incorporating these methods with other anti
      neoplastic interventions ultimately will ensure the best responses and patient
      outcomes.

PMID- 22456230
TI  - Inflammation modulates human HDL composition and function in vivo.
AB  - OBJECTIVES: Inflammation may directly impair HDL functions, in particular reverse
      cholesterol transport (RCT), but limited data support this concept in humans.
      METHODS AND RESULTS: We employed low-dose human endotoxemia to assess the effects
      of inflammation on HDL and RCT-related parameters in vivo. Endotoxemia induced
      remodelling of HDL with depletion of pre-beta1a HDL particles determined by 2-D
      gel electrophoresis (-32.2+/-9.3% at 24 h, p<0.05) as well as small (-23.0+/
      5.1%, p<0.01, at 24 h) and medium (-57.6+/-8.0% at 16 h, p<0.001) HDL estimated
      by nuclear magnetic resonance (NMR). This was associated with induction of class
      II secretory phospholipase A2 (~36 fold increase) and suppression of
      lecithin:cholesterol acyltransferase activity (-20.8+/-3.4% at 24 h, p<0.01) and
      cholesterol ester transfer protein mass (-22.2+/-6.8% at 24 h, p<0.001). The HDL
      fraction, isolated following endotoxemia, had reduced capacity to efflux
      cholesterol in vitro from SR-BI and ABCA1, but not ABCG1 transporter cell models.
      CONCLUSIONS: These data support the concept that "atherogenic-HDL dysfunction"
      and impaired RCT occur in human inflammatory syndromes, largely independent of
      changes in plasma HDL-C and ApoA-I levels.

PMID- 22456232
TI  - Diabetes: treating hypertension.
AB  - INTRODUCTION: Among people with diabetes, about 40% of those aged 45 years, and
      more than 60% of those aged 75 years or over, will have a blood pressure over
      140/90 mmHg. Major cardiac events occur in approximately 5% of people with
      diabetes and untreated hypertension each year, and the risk is higher in those
      with other risk factors, such as diabetic nephropathy. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of antihypertensives in people with diabetes and
      hypertension? What are the effects of different blood pressure targets in people
      with diabetes and hypertension? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to April 2011 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 24
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. CONCLUSIONS: In this systematic review, we present information relating
      to the effectiveness and safety of the following interventions: alpha-blockers,
      angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE)
      inhibitors, beta-blockers, blood pressure targets (lower or higher), calcium
      channel blockers, and diuretics.

PMID- 22456233
TI  - Resistive switching memory properties of layer-by-layer assembled enzyme
      multilayers.
AB  - The properties of enzymes, which can cause reversible changes in currents through
      redox reactions in solution, are of fundamental and practical importance in bio
      electrochemical applications. These redox properties of enzymes are often
      associated with their charge-trap sites. Here, we demonstrate that reversible
      changes in resistance in dried lysozyme (LYS) films can be generated by an
      externally applied voltage as a result of charge trap/release. Based on such
      changes, LYS can be used as resistive switching active material for nonvolatile
      memory devices. In this study, cationic LYS and anionic poly(styrene sulfonate)
      (PSS) layers were alternately deposited onto Pt-coated silicon substrates using a
      layer-by-layer assembly method. Then, top electrodes were deposited onto the top
      of LYS/PSS multilayers to complete the fabrication of the memory-like device. The
      LYS/PSS multilayer devices exhibited typical resistive switching characteristics
      with an ON/OFF current ratio above 10(2), a fast switching speed of 100 ns and
      stable performance. Furthermore, the insertion of insulating polyelectrolytes
      (PEs) between the respective LYS layers significantly enhanced the memory
      performance of the devices showing a high ON/OFF current ratio of ~10(6) and low
      levels of power consumption.

PMID- 22456234
TI  - Biological treatment of TMAH (tetra-methyl ammonium hydroxide) in a full-scale
      TFT-LCD wastewater treatment plant.
AB  - This study evaluated biological treatment of TMAH in a full-scale methanogenic up
      flow anaerobic sludge blanket (UASB) followed by an aerobic bioreactor. In
      general, the UASB was able to perform a satisfactory TMAH degradation efficiency,
      but the effluent COD of the aerobic bioreactor seemed to increase with an
      increased TMAH in the influent wastewater. The batch test results confirmed that
      the UASB sludge under methanogenic conditions would be favored over the aerobic
      ones for TMAH treatment due to its superb ability of handling high strength of
      TMAH-containing wastewaters. Based on batch experiments, inhibitory chemicals
      present in TFT-LCD wastewater like surfactants and sulfate should be avoided to
      secure a stable methanogenic TMAH degradation. Finally, molecular monitoring of
      Methanomethylovorans hollandica and Methanosarcina mazei in the full-scale plant,
      the dominant methanogens in the UASB responsible for TMAH degradation, may be
      beneficial for a stable TMAH treatment performance.

PMID- 22456235
TI  - Modification of tryptophan transport system and its impact on production of L
      tryptophan in Escherichia coli.
AB  - The production of L-tryptophan through chemical synthesis, direct fermentation,
      bioconversion and enzymatic conversion has been reported. However, the role of
      transport system for aromatic amino acids in L-tryptophan producing strains has
      not been fully explored. In this study, the fact was revealed that L-tryptophan
      production and cell growth were affected by the modification of transport systems
      based on YddG functioning as aromatic amino acid excretion and AroP functioning
      as general aromatic amino acid permease. Through comparing glucose conversion
      rates of recombinant strains such as Escherichia coli TRTH DeltaaroP, E. coli
      TRTH-Y, and E. coli TRTH DeltaaroP-Y, the moderate modification of transport
      system resulted in the metabolic flux redistribution of L-tryptophan biosynthesis
      pathway. In the fed-batch fermentation by E. coli TRTH and E. coli TRTH-Y in 30
      liter fermentor, the final production of L-tryptophan fermented by E. coli TRTH-Y
      was 36.3 g/L, which was 12.6% higher than fermentation by E. coli TRTH.

PMID- 22456236
TI  - Effect of substrate load and nutrients concentration on the polyhydroxyalkanoates
      (PHA) production using mixed consortia through wastewater treatment.
AB  - Production of biodegradable plastics in the form of polyhydroxyalkanoates (PHA)
      especially from renewable substrates is gaining interest. The present work mainly
      aims to investigate the influence of substrate load and nutrient concentration
      (nitrogen and phosphorous) on PHA production using wastewater as substrate and
      mixed culture as biocatalyst. PHA accumulation was high at higher substrate load
      [OLR3, 40.3% of dry cell weight (DCW)], low nitrogen (N(1), 45.1% DCW) and low
      phosphorous (P(1), 54.2% DCW) conditions. With optimized nutrient conditions
      production efficiency increased by 14%. Fractional composition of PHA showed co
      polymer [poly(beta-OH) butyrate-co-poly(beta-OH) valerate, P3(HB-co-HV)] contains
      PHB (88%) in more concentration compared to PHV (8%). Dehydrogenase and
      phosphatase enzymatic activities were monitored during process operation. Good
      substrate degradation (as COD) of 75% was registered during PHA production. The
      phylogenetic profile of 16S rRNA sequencing showed the dominance of Firmicutes
      (71.4%) and Proteobacteria (28.6%), which are known to involve in PHA
      accumulation and waste treatment.

PMID- 22456237
TI  - Removal of water-insoluble Sudan dyes by Shewanella oneidensis MR-1.
AB  - Decolorization of water-insoluble Sudan dyes was studied with Shewanella
      oneidensis MR-1, which removed 66.8%, 43.4%, 56.0% and 33.7% Sudan I-IV in 104 h,
      respectively and reduced Sudan I to aniline and 1-amino-2-naphthol. Lactate was
      identified as the most efficient electron donor for Sudan I reduction. Improved
      reduction performance was obtained in the presence of higher lactate or biomass
      concentration. The correlation between specific reduction rate and initial Sudan
      I concentration could be described with Michaelis-Menten kinetics (V(max)=1.8 mg
      Sudan I mg cell(-1) h(-1) and K(m)=5.3 mg l(-1)). The addition of anthraquinone-2
      sulfonate stimulated the reduction significantly whereas the presence of 2
      hydroxy-1,4-naphthoquinone had little enhancing effect. The main azoreductase
      activity was found with membrane-bound proteins of MR-1 and no reduction occurred
      when Sudan I was incubated with cell extracts. These data indicated for the first
      time that Shewanella could reduce solid-phase Sudan dye particles.

PMID- 22456238
TI  - Integrated analysis of gene copy number, copy neutral LOH, and microRNA profiles
      in adult acute lymphoblastic leukemia.
AB  - We adopted an integrated analysis of gene copy number alterations (CNAs), copy
      number neutral loss of heterozygosity (CNN LOH), and microRNA (miRNA) profiling
      in 21 adult acute lymphoblastic leukemia (ALL) patients. This study revealed the
      most frequent CNAs to be at chromosomes 9p, 7, and 17 and recurrent CNN LOH at
      5p, 9p, and Xq. As for the most differentially expressed miRNAs, they included 8
      upregulated and 14 downregulated miRNAs, of which miR-148a at 7p15.2, miR-22 at
      17p13.3, miR-223 at Xq12, as well as miR-101-2 at 9p24.1 exhibited recurrent CNAs
      or CNN LOH. miR-101-2 was recurrently downregulated, and although the related CNN
      LOH was detected only in BCR-ABL1 negative cases (2/14), deletions of miR-101-2
      were observed solely in BCR-ABL1 positive cases (4/7). Finally, BCR-ABL1 positive
      cases, in contrast to negative ones, were characterized by slightly, but still
      significantly, higher expression levels of miR-29b.

PMID- 22456239
TI  - Alcohol-related risk of driver fatalities: an update using 2007 data.
AB  - OBJECTIVE: The purpose of this study was to determine whether the relative risk
      of being involved in an alcohol-related crash has changed over the decade from
      1996 to 2007, a period during which there has been little evidence of a reduction
      in the percentage of all fatal crashes involving alcohol. METHOD: We compared
      blood-alcohol information for the 2006 and 2007 crash cases (N = 6,863, 22.8% of
      them women) drawn from the U.S. Fatality Analysis Reporting System (FARS) with
      control blood-alcohol data from participants in the 2007 U.S. National Roadside
      Survey (N = 6,823). Risk estimates were computed and compared with those
      previously obtained from the 1996 FARS and roadside survey data. RESULTS:
      Although the adult relative risk of being involved in a fatal alcohol-related
      crash apparently did not change from 1996 to 2007, the risk for involvement in an
      alcohol-related crash for underage women has increased to the point where it has
      become the same as that for underage men. Further, the risk that sober underage
      men will become involved in a fatal crash has doubled over the 1996-2007 period.
      CONCLUSIONS: Compared with estimates obtained from a decade earlier, young women
      in this study are at an increased risk of involvement in alcohol-related crashes.
      Similarly, underage sober drivers in this study are more at risk of involvement
      in a crash than they were a decade earlier.

PMID- 22456240
TI  - Intimate partner violence and patterns of alcohol abuse and dependence criteria
      among women: a latent class analysis.
AB  - OBJECTIVE: Intimate partner violence (IPV) is a major public health issue, yet
      little is known about the association between IPV victimization and problem
      drinking among women. Study objectives were to (a) identify subtypes of problem
      drinking among women according to abuse and dependence criteria from the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV);
      (b) examine the association between recent IPV and the problem drinking classes;
      and (c) evaluate major depressive disorder (MDD) as a mediator of the IPV-alcohol
      relationship. METHOD: Data come from a cohort of 11,782 female current drinkers
      participating in Wave 2 (2004-2005) of the National Epidemiologic Survey on
      Alcohol and Related Conditions. Latent class analysis was used to group
      participants into problem drinking classes according to 11 DSM-IV abuse and
      dependence criteria. The IPV measure was derived from six questions regarding
      abusive behaviors perpetrated by a romantic partner in the past year. Past-year
      MDD was assessed according to DSM-IV criteria. Latent class regression was used
      to test the association between drinking class and IPV. RESULTS: Three classes of
      problem drinkers were identified: Severe (Class 1: 1.9%; n = 224), moderate
      (Class 2: 14.2%; n = 1,676), and nonsymptomatic (Class 3: 83.9%; n = 9,882). Past
      year IPV was associated with severe and moderate classes (severe: adjusted odds
      ratio [aOR] = 5.70, 95% CI [3.70, 8.77]; moderate: aOR = 1.92, 95% CI [1.43,
      2.57]). Past-year MDD was a possible mediator of the IPV-drinking class
      relationship. CONCLUSIONS: Results indicate a strong association between recent
      IPV and problem drinking class membership. This study offers preliminary evidence
      that programs aimed at preventing problem drinking among women should take IPV
      and MDD into consideration.

PMID- 22456241
TI  - Alcohol policies and practices among four-year colleges in the United States:
      prevalence and patterns.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of college
      alcohol policies and practices and to identify patterns of policies/practices
      across colleges. METHOD: An online survey of administrators at a random sample of
      351 4-year U.S. colleges was conducted in 2008. The prevalence of 31 alcohol
      policies and practices was assessed as well as differences across size and type
      of colleges. Latent class analyses identified classes of colleges based on their
      alcohol policies/practices. RESULTS: The majority of colleges prohibit alcohol
      use at sporting events, whereas less than half prohibit alcohol use at fraternity
      and sorority events. Less than half of the colleges also prohibit alcohol
      advertising in/on campus newspapers and radio stations. Small colleges are more
      likely than large colleges to prohibit alcohol use at tailgating events and to
      prohibit newspaper alcohol advertising. Public colleges are more likely than
      private colleges to prohibit alcohol use in dorms but less likely to prohibit
      alcohol advertising. We identified four classes of colleges-the largest class
      (38%) was characterized by having many alcohol policies/practices, the smallest
      class (13%) had none or few alcohol policies/practices, and the remainder fit
      into two middle classes that had certain policies/practices in place but lacked
      others. CONCLUSIONS: Most colleges report implementing some alcohol policies/
      practices but are lacking others. Only two of every five colleges fit into a
      class that has many alcohol policies. More studies are needed to validate our
      findings and assess whether certain policies/practices and patterns of policies
      are associated with reducing student alcohol consumption and related problems.

PMID- 22456242
TI  - Relationship of substance abuse to dependence in the U.S. general population.
AB  - OBJECTIVE: The diagnostic categories of the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, for substance abuse and dependence are commonly
      used in clinical work and research studies, but whether abuse and dependence
      represent two different syndromes has been debated. The purpose of this article
      is to investigate the relationship of substance abuse and dependence for
      cannabis, cocaine, stimulants and sedatives among lifetime users of these
      substances in the National Epidemiologic Survey on Alcohol and Related
      Conditions, a nationally representative survey conducted in 2001-2002. METHOD:
      The multiple indicators multiple causes (MIMIC) model addresses three sets of
      relationships: those between (1) diagnostic criteria and latent factors, (2)
      latent factors and covariates, and (3) criteria and covariates. This approach
      allows for the detection of and compensation for noninvariance of the measurement
      of criteria across subgroups. RESULTS: Compared with one-factor models, two
      factor models (factors roughly corresponding to abuse and dependence) fit
      significantly better across all substances, with abuse and dependence factors
      highly correlated. The MIMIC model indicated that race/ethnicity, age, income,
      and marital status showed some differential relationships across substance
      groups, although most covariates showed similar associations to dependence and
      abuse factors. Noninvariance of criteria measurement by demographic covariates
      was most pronounced for cannabis abuse and dependence criteria. CONCLUSIONS: The
      general relationship of abuse to dependence was consistent across substances.
      Results were equivocal on the value of retaining separate factors; therefore,
      investigating the relationships of specific genetic variants and treatment
      outcomes to dimensional indicators of abuse, dependence, and measures combining
      these criteria is warranted. Measurement of cannabis abuse and dependence
      criteria appears most affected by demographic characteristics.

PMID- 22456244
TI  - Association between alcohol screening scores and alcohol-related risks among
      female veterans affairs patients.
AB  - OBJECTIVE: Evidence-based brief interventions for primary care patients with at
      risk drinking include personalized feedback on alcohol-related risks, yet little
      is known about associations between alcohol screening scores and outcomes among
      women. This study evaluated associations between scores on the three-item Alcohol
      Use Disorders Identification Test-consumption (AUDIT-C) questionnaire and self
      reported alcohol-related risks and consequences among veteran women. METHOD:
      Female outpatients from an urban Veterans Affairs facility were mailed annual
      surveys (1998-2000) (response rates: 65% Years 1 and 2, 55% Year 3). Measures
      were obtained from each respondent's first completed survey and included a gender
      specific AUDIT-C (0-12 points), self-reported alcohol-related consequences,
      problem drinking or other drug use, and health risks. The prevalence of each
      outcome across AUDIT-C score groups (0, 1-2, 3, 4, 5-7, 8-12) was estimated using
      logistic regression, adjusting for age, race, and marital status. RESULTS: Among
      2,670 respondents, 23.7% screened positive for alcohol misuse (AUDIT-C >=3). For
      three out of the five alcohol-related consequences (tolerance, blackouts, felt
      needed to cut down), adjusted prevalence increased at AUDIT-C scores of 3 or
      more. The remaining alcohol-related consequences (morning eye openers,
      family/friends worried) increased at scores of 4 or more, as did self-reported
      problem drinking or other drug use. Associations between health risks (two or
      more sexual partners, sexually transmitted diseases, injuries, domestic violence,
      hepatitis/cirrhosis) and AUDIT-C scores were less consistent, but prevalence
      generally increased at scores of 5 or more. CONCLUSIONS: Increasing scores on the
      AUDIT-C reflect increasing prevalence of self-reported alcohol-related risks and
      consequences among women. These results provide clinicians with gender-specific
      information on alcohol-related risks that could be incorporated into brief
      interventions.

PMID- 22456243
TI  - Examining explanatory mechanisms of the effects of early alcohol use on young
      adult alcohol dependence.
AB  - OBJECTIVE: This study examined potential explanatory mechanisms linking childhood
      alcohol use onset and chronicity of adult alcohol dependence by testing the
      following three competing hypotheses: (1) a marker hypothesis, where early onset
      of alcohol use may be simply a marker for other factors that have been linked to
      both age at initiation and adult alcohol problems; (2) a compromised development
      hypothesis, where early alcohol initiation may interfere with adolescent
      development, which can lead to later alcohol problems; and (3) an increased
      substance use hypothesis, where early onset of alcohol use may lead to increased
      substance use in adolescence and, in turn, chronic alcohol dependence. METHOD:
      Data came from a longitudinal community sample of 808 participants recruited at
      age 10 in 1985. Participants were followed through age 33 in 2008 with 92%
      retention. RESULTS: Childhood onset of alcohol use (before age 11), when compared
      with initiation during adolescence, predicted an increased chronicity of adult
      alcohol dependence, even after accounting for the hypothesized confounds from the
      marker hypothesis. In addition, adolescent compromised functioning did not
      mediate this relationship between early alcohol use and chronicity of adult
      dependence (Hypothesis 2), nor did adolescent substance use (Hypothesis 3).
      However, compromised functioning and substance use in adolescence predicted
      increased chronicity of alcohol dependence in young adulthood. CONCLUSIONS:
      Prevention efforts as early as the elementary grades should focus on delaying the
      onset of alcohol use and reducing substance use in adolescence as well as
      improving school functioning, reducing adolescent problem behaviors, and
      targeting adolescent peer networks.

PMID- 22456245
TI  - Impact of sexual orientation and co-occurring disorders on chemical dependency
      treatment outcomes.
AB  - OBJECTIVE: The aims of this study were to compare client characteristics at
      admission to chemical dependency (CD) treatment by sexual orientation, examine
      sexual orientation as a predictor of co-occurring CD and mental health problems
      (hereafter referred to as co-occurring disorders [COD]), and to examine the
      effect of sexual orientation and COD on 1-year CD treatment outcomes (treatment
      completion, treatment reentry, and arrest) among men and women. METHOD: This
      retrospective cohort study used 2004-2008 data from publicly funded CD treatment
      programs in Washington State (n = 69,525 clients). Bivariate comparisons were
      made using chi-square tests; logistic and Cox regressions were to estimate risk
      in multivariate analyses. RESULTS: Risk factors associated with sexual minority
      status (lesbian/gay/bisexual) included COD, primary drug (vs. alcohol) use, and
      greater substance use. In multivariate analyses, sexual minority clients were
      more than twice as likely as their heterosexual counterparts to have COD. COD,
      but not sexual orientation, negatively predicted treatment completion and arrest
      overall in the year following treatment among male and female clients and
      positively predicted treatment reentry and intimate partner violence-related
      arrest among women. COD moderated the effect of sexual orientation on arrest; gay
      men with COD were less likely to be arrested, particularly for substance use and
      other violence-related crimes. CONCLUSIONS: These findings highlight the
      importance of assessing mental health among sexual minority clients in treatment
      settings and addressing issues specific to both female and male sexual
      minorities.

PMID- 22456246
TI  - Advancing recovery: implementing evidence-based treatment for substance use
      disorders at the systems level.
AB  - OBJECTIVE: A multisite evaluation examined the process and outcomes of Advancing
      Recovery, a Robert Wood Johnson Foundation initiative to overcome barriers to
      implementing evidence-based treatments within alcohol and drug treatment systems.
      METHOD: We report findings from a 3-year, mixed-method study of how treatment
      systems promoted two evidence-based practices: medication-assisted treatment and
      continuing care management. We compared outcomes and implementation strategies
      across 12 state/county agencies responsible for alcohol and drug treatment and
      their selected treatment centers. Each partnership received 2 years of financial
      and technical support to increase adoption of evidence-based treatments. RESULTS:
      Partnerships flexibly applied the Advancing Recovery model to promote the
      adoption of evidence-based treatments. Most sites achieved a measurable increase
      in the numbers of patients served with evidence-based practices, up from a
      baseline of virtually no use. Rates of adopting medication-based treatments were
      higher than those for continuing care management. Partnerships used a menu of top
      down and bottom-up strategies that varied in specifics across sites but shared a
      general process of incremental testing and piecemeal adaptation. CONCLUSIONS:
      Supported partnerships between providers and policymakers can achieve wider
      adoption of evidence-based treatment practices. Systems change unfolds through a
      trial-and-error process of adaptation and political learning that is unique to
      each treatment system. This leads to considerable state and local variation in
      implementation strategies and outcomes.

PMID- 22456247
TI  - Do peers' parents matter? A new link between positive parenting and adolescent
      substance use.
AB  - OBJECTIVE: Although studies have demonstrated that an adolescent's parents and
      friends both influence adolescent substance use, it is not known whether the
      parenting experienced by one's friends also affects one's own use. Drawing on
      conceptions of shared parenting and the tenets of coercion theory, we
      investigated the extent to which three domains of parenting behaviors (parental
      knowledge, inductive reasoning, and consistent discipline) influenced the
      alcohol, cigarette, and marijuana use of not only their own adolescent children
      but also of members of their adolescents' friendship groups. METHOD: Analyses of
      friendship nominations within each of two successive ninth-grade cohorts in 27
      Iowa and Pennsylvania schools (N = 7,439 students, 53.6% female) were used to
      identify 897 friendship groups. Hierarchical logistic regression models were used
      to examine prospective associations between 9th-grade friendship group-level
      parenting behaviors and adolescent self-reported alcohol, cigarette, and
      marijuana use in 10th grade. RESULTS: Adolescent substance use in 10th grade was
      significantly related to parenting behaviors of friends' parents, after
      controlling for adolescents' reports of their own substance use and their own
      parents' behaviors at the 9th grade level. These associations were particularly
      strong for parents' knowledge about their children and use of inconsistent
      discipline strategies. Significant interaction effects indicated that these
      relationships were strongest when adolescents received positive parenting at
      home. Some, but not all, of the main effects of friends' parents' parenting
      became nonsignificant after friends' substance use in ninth grade was included in
      the model. CONCLUSIONS: The findings suggest that the parenting style in
      adolescents' friends' homes plays an important role in determining adolescent
      substance use. Implications of the joint contribution of parents and peers for
      prevention and intervention are discussed.

PMID- 22456248
TI  - Using parental profiles to predict membership in a subset of college students
      experiencing excessive alcohol consequences: findings from a longitudinal study.
AB  - OBJECTIVE: Previous research identified a high-risk subset of college students
      experiencing a disproportionate number of alcohol-related consequences at the end
      of their first year. With the goal of identifying pre-college predictors of
      membership in this high-risk subset, the present study used a prospective design
      to identify latent profiles of student-reported maternal and paternal parenting
      styles and alcohol-specific behaviors and to determine whether these profiles
      were associated with membership in the high-risk consequences subset. METHOD: A
      sample of randomly selected 370 incoming first-year students at a large public
      university reported on their mothers' and fathers' communication quality,
      monitoring, approval of alcohol use, and modeling of drinking behaviors and on
      consequences experienced across the first year of college. RESULTS: Students in
      the high-risk subset comprised 15.5% of the sample but accounted for almost half
      (46.6%) of the total consequences reported by the entire sample. Latent profile
      analyses identified four parental profiles: positive pro-alcohol, positive anti
      alcohol, negative mother, and negative father. Logistic regression analyses
      revealed that students in the negative-father profile were at greatest odds of
      being in the high-risk consequences subset at a follow-up assessment 1 year
      later, even after drinking at baseline was controlled for. Students in the
      positive pro-alcohol profile also were at increased odds of being in the high
      risk subset, although this association was attenuated after baseline drinking was
      controlled for. CONCLUSIONS: These findings have important implications for the
      improvement of existing parent- and individual-based college student drinking
      interventions designed to reduce alcohol-related consequences.

PMID- 22456249
TI  - Developmental consistency in associations between depressive symptoms and alcohol
      use in early adolescence.
AB  - OBJECTIVE: Despite frequent theorizing, prior literature on the association
      between depressive symptoms and alcohol use in adolescence has been inconsistent.
      Yet studies have varied widely with respect to age at assessments, time frame of
      prediction, and controls for comorbid conditions and demographic factors. The
      current study examined whether the associations between depressive symptoms and
      alcohol use were similar in valence and magnitude over a 4-year period in early
      adolescence. METHOD: A sample of 521 young adolescents and their parents were
      interviewed every year from sixth (Mage = 12.0 years) through ninth grades. At
      each interview, symptom counts on depressive and conduct disorders were generated
      from the Diagnostic Interview Schedule for Children. Adolescents also reported on
      their alcohol use, which was converted to a binary variable. Autoregressive,
      cross-lagged panel models specifying depressive and conduct disorder symptoms as
      predictors of alcohol use 1 year later with equality constraints were tested and
      compared with models allowing path coefficients to vary over time. RESULTS: For
      youth self-report, depressive symptoms were positively associated with alcohol
      use 1 year later over and above conduct problems and earlier alcohol use
      throughout early adolescence. By parental report, only very early adolescent
      depressive symptoms (sixth to seventh grades) were associated with alcohol use.
      Gender did not moderate findings for analyses with self- or parental-report data.
      CONCLUSIONS: These results indicate that, even in the context of conduct disorder
      symptoms, depressive symptoms are important indicators of risk for use of alcohol
      across early adolescence.

PMID- 22456250
TI  - Trends in alcohol- and drug-related emergency department and primary care visits:
      data from four U.S. national surveys (1995-2010).
AB  - OBJECTIVE: The purpose of this study was to update trends in alcohol- and drug
      related emergency department and primary care visits over the last 15 years in
      the United States. METHOD: A trend analysis was conducted on substance-related
      health services visits, based on self-reported alcohol or other drug use within 6
      hours before an injury and/or illness event, from four National Alcohol Surveys:
      1995, 2000, 2005, and 2010. RESULTS: A significant upward trend was found from
      1995 to 2010 in alcohol-related emergency department visits but not in alcohol
      related primary care visits. The odds of an alcohol-related emergency department
      visit doubled between 1995 and 2010 (odds ratio = 2.36). No significant trend was
      found in either drug-related emergency department or drug-related primary care
      visits between 1995 and 2010. CONCLUSIONS: These data suggest that alcohol
      related emergency department visits have increased significantly over the past 15
      years, whereas drug-related emergency department visits may have stabilized.
      These findings underscore the opportunity provided by the emergency department
      for screening and brief intervention for alcohol-related problems and suggest
      that Healthy People 2010 objectives calling for a reduction in substance-related
      emergency department visits were not realized. Thus, it might be prudent to
      adjust Healthy People 2020 objectives accordingly.

PMID- 22456251
TI  - Effects of age and life transitions on alcohol and drug treatment outcome over
      nine years.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of age, common
      life transitions, treatment, and social support on outcomes 5-9 years after
      alcohol and other drug (AOD) treatment intake. METHOD: Participants were patients
      from a large outpatient AOD treatment program in an integrated health plan. There
      were 1,951 participants interviewed at intake, of whom 1,646 (84%) completed one
      or more telephone follow-up interviews at 5, 7, and 9 years. Measures included
      AOD use based on the Addiction Severity Index; treatment; and changes in marital,
      employment, and health status in the years between each follow-up. We compared
      participants by age group (18-39, 40-54, and >=55 years old at intake) and
      examined factors (time invariant and time varying) associated with outcomes at 5,
      7, and 9 years by fitting mixed-effects logistic random intercept models.
      RESULTS: Changes in marital, employment, and health status varied significantly
      by age. Factors associated with remission across Years 5-9 included being in the
      middle-aged versus younger group (p < .001); female gender (p < .001); not losing
      a partner to separation, divorce, or death (p < .001); not experiencing a decline
      in health (p = .021); having any close friends supportive of recovery (p < .001);
      and not having any close friends who encourage AOD use (p < .001). Additional
      predictors, including employment changes, varied by drug versus alcohol
      abstinence outcome measures. CONCLUSIONS: Negative life transitions vary by age
      and are associated with worse outcomes. Older age and social support are
      associated with long-term AOD remission and abstinence. Findings inform treatment
      strategies to enhance recovery across the life span.

PMID- 22456252
TI  - Self-efficacy and HIV risk behaviors among heroin users in Taiwan.
AB  - OBJECTIVE: This study examined the predictors of self-efficacy in reducing risky
      injection behaviors among heroin users receiving methadone maintenance treatment
      (MMT). METHOD: The Methadone Maintenance Treatment Outcome Study was an 18-month
      prospective study from March 2007 to July 2008. Data collection was conducted in
      the substance use disorders treatment outpatient clinics of three hospitals in
      southern Taiwan. A total of 368 opioid-dependent heroin users (13.6% women) were
      interviewed at baseline and at 3-, 6-, 9-, 12-, 15- and 18-month follow-ups. The
      level of self-efficacy in reducing risky injection behaviors was repeatedly
      assessed using the Self-Efficacy Scale for HIV Risk Behaviors. Demographic and
      substance use characteristics, HIV serostatus, family function, depression, and
      pros and cons of heroin use were collected at baseline, and methadone dosage at
      each follow-up interview and the duration of retention in the MMT program were
      also recorded. RESULTS: The results of the generalized estimating equation
      indicated that a lower educational level, concurrent methamphetamine use, a
      younger age at first heroin use, a lower methadone dosage, a higher level of
      depression, and a shorter duration of retention in the MMT program were
      predictive of a lower level of self-efficacy in reducing risky injection
      behaviors. CONCLUSIONS: This study found that personal and MMT-related factors
      were predictive of a lower level of self-efficacy among heroin users receiving
      MMT. Programs implemented to promote a higher level of self-efficacy should be
      provided to heroin users in the MMT program.

PMID- 22456253
TI  - A systematic review of family-based interventions targeting alcohol misuse and
      their potential to reduce alcohol-related harm in indigenous communities.
AB  - OBJECTIVE: Alcohol misuse is a major risk factor for harm in indigenous
      communities. The indigenous family unit is often the setting for, and is most
      adversely affected by, alcohol-related harm. Therefore, family-based alcohol
      interventions offer great potential to reduce alcohol-related harm in indigenous
      communities. This systematic review aims to identify peer-reviewed published
      evaluations of family-based alcohol interventions, critique the methodological
      quality of those studies, describe their intervention characteristics, and
      identify which interventions appear most promising to reduce alcohol-related harm
      in indigenous communities. METHOD: Eleven electronic databases were searched. The
      reference lists of reviews of family-based approaches focused on alcohol
      interventions were hand-searched for additional relevant studies not identified
      by the electronic database search. RESULTS: Initially, 1,369 studies were
      identified, of which 21% (n = 142) were classified as intervention studies.
      Nineteen intervention studies were family-based alcohol interventions. Eleven of
      these studies included family members in the treatment of problem drinkers, and
      eight studies specifically targeted family members of problem drinkers.
      Methodological quality of studies varied, particularly in relation to study
      design, including confounding variables in the analyses, and follow-up rates.
      CONCLUSIONS: The evidence for the effectiveness of family-based alcohol
      interventions is less than optimal, although the reviewed studies did show
      improved outcomes. Given the important role of family in indigenous communities,
      there is merit in exploring family-based approaches to reduce alcohol-related
      harms. Tailored family-based approaches should be developed that include direct
      consultation with targeted indigenous communities.

PMID- 22456254
TI  - Association between social influences and drinking outcomes across three years.
AB  - OBJECTIVE: Multiple studies have shown social network variables to mediate and
      predict drinking outcome, but, because of self-selection biases, these studies
      cannot reliably determine whether the influence is causal or correlational. The
      goal of this study was to evaluate evidence for a causal role for social network
      characteristics in determining long-term outcomes using state-of-the-art
      statistical methods. METHOD: Outpatient and aftercare clients enrolled in Project
      MATCH (N = 1,726) were assessed at intake and at 3, 6, 9, 12, and 15 months; the
      outpatient sample was also followed to 39 months. Generalized linear modeling
      with propensity stratification tested whether changes in social network ties
      (i.e., number of pro-abstainers and pro-drinkers) at Month 9 predicted percentage
      of days abstinent and drinks per drinking day at 15 and 39 months, covarying for
      Alcoholics Anonymous (AA) attendance at Month 9. RESULTS: An increase in the
      number of pro-drinkers predicted worse drinking outcomes, measured by percentage
      of days abstinent and drinks per drinking day, at Months 15 and 39 (p < .0001).
      An increase in the number of pro-abstainers predicted more percentage of days
      abstinent for both time periods (p < .01). The social network variables uniquely
      predicted 5%-12% of the outcome variance; AA attendance predicted an additional
      1%-6%. CONCLUSIONS: Network composition following treatment is an important and
      plausibly causal predictor of alcohol outcome across 3 years, adjusting for
      multiple confounders. The effects are consistent across patients exhibiting a
      broad range of alcohol-related impairment. Results support the further
      development of treatments that promote positive social changes and highlight the
      need for additional research on the determinants of social network changes.

PMID- 22456255
TI  - Do protective behavioral strategies moderate the relationship between negative
      urgency and alcohol-related outcomes among intercollegiate athletes?
AB  - OBJECTIVE: The purpose of this study was to examine the moderating effect of
      protective behavioral strategies on the relationship between negative urgency and
      alcohol outcomes. METHOD: Participants were college students who endorsed
      participating in club/intramural or varsity athletics. The students (N = 234;
      73.9% female) completed measures of negative urgency, protective behavioral
      strategies, alcohol use, and alcohol-related problems. Separate hierarchical
      multiple regression analyses were conducted for each subscale of the Protective
      Behavioral Strategies Scale to test for moderation. RESULTS: Results indicated
      that protective behavioral strategies aimed at serious harm reduction moderated
      the relationship between negative urgency and alcohol use, whereas strategies
      aimed at avoiding excessive or rapid drinking moderated the relationship between
      negative urgency and alcohol-related problems. Strategies that involved planning
      drinking activities in advance did not moderate the relationship between negative
      urgency and alcohol outcomes. CONCLUSIONS: The current investigation provides
      further evidence for the role of protective behavioral strategies against known
      risk factors for alcohol use and related problems. Further, the paper suggests
      that type of strategy used matters when attempting to mitigate the relationship
      between negative urgency and alcohol outcomes. Limitations and future directions
      are discussed.

PMID- 22456256
TI  - Motivation to change as a mediator for the longitudinal relationships of gender
      and alcohol severity with one-year drinking outcome.
AB  - OBJECTIVE: We examined whether motivation to change mediated the relationships
      between gender and baseline alcohol severity with drinking outcome at 12-month
      follow-up in a longitudinal community sample. METHOD: Data were from baseline and
      12-month interviews from the Rural Alcohol Study, a probability sample of rural
      and urban at-risk drinkers (N = 733) from six southern states. At-risk drinkers
      were identified through a telephone-screening interview. Measures of motivation
      (problem recognition and taking action) were the resultant two factors derived
      from the Stages of Change Readiness and Treatment Eagerness Scale. Items on
      social consequences of drinking measured alcohol severity. Structural equation
      models examined relationships between baseline alcohol severity and motivation
      with drinks per drinking day at 12 months. RESULTS: We identified significant,
      direct paths between drinking at 12 months and alcohol severity and taking action
      with an unstandardized estimate of 0.116 (p < .05), alcohol severity and problem
      recognition (0.423, p < .01), and each of the two "motivation" latent constructs
      problem recognition (1.846, p < .01) and taking action (-0.660, p < .01).
      Finally, the combined direct and negative effect of gender on alcohol consumption
      at 12-month follow-up was statistically significant, with an unstandardized
      estimate of -0.970 (p < .01). CONCLUSIONS: The current study offers evidence for
      motivation to change as a viable mechanism through which alcohol severity is
      associated with subsequent drinking outcomes. More research is needed to further
      explore the persistence of motivation to change on drinking outcomes over time.

PMID- 22456257
TI  - Prevalence of bicuspid aortic valve in patients presenting with subarachnoid
      hemorrhage related to an intracerebral aneurysm.

PMID- 22456258
TI  - Questionnaire survey on depression for patients with heart failure: validation
      for selecting appropriate cut-off points.

PMID- 22456259
TI  - Fatal Tako-Tsubo cardiomyopathy recurrence after beta2-agonist administration.

PMID- 22456260
TI  - Endocarditis due to a stealthy bug.

PMID- 22456261
TI  - Is interleukin-6 circulating levels associated with coronary artery disease?

PMID- 22456262
TI  - The research collaboration in Chinese cardiology and cardiovasology field.
AB  - BACKGROUND: China has become the world's second-largest economy after the United
      States since 2010. The cardiovascular diseases in have deteriorated significantly
      in resent 20 years. There is few published report about collaboration in Chinese
      Cardiology and Cardiovasology (C&C) field so far. The current study reveals the
      status of the collaboration activities in Chinese C&C field. METHODS: Articles
      published in 5 journals related to C&C from 2000 to 2010 were retrieved from
      China National Knowledge Infrastructure (CNKI) and VIP Journal Integration
      Platform(VJIP). Methods such as co-authorship, co-word analysis, centrality, k
      core, m-slice were used in this study. RESULTS: Although the percentage of co
      authored papers and the average number of authors per paper in Chinese C&C field
      were generally increasing, the geographic distribution of the research
      collaboration activities was extremely uneven. There were 87 authors and 5
      institutions ranking in top 1% of all the three centralities but 92.8% authors
      belonged to 10-Core and below. 90.93% authors are among 1-slice, 2-slice and 3
      slice. We found 63 cohesive research groups in the focuses of research
      collaboration for Coronary artery disease and myocardial infarction, etc.
      CONCLUSION: The government should provide important role in supporting or
      encouraging the research collaboration among different regional areas. Based on
      the author ranking in the centralities, we will be able to select academic
      leaders more easily. The research studies in the field of collaboration network
      will provide important role to assist researchers to master the forefront
      research subjects, and to help research scientists to apply for scientific
      project funding.

PMID- 22456263
TI  - Acoustic cardiography helps to identify heart failure and its phenotypes.
AB  - BACKGROUND: The prevalence of heart failure (HF) is increasing as the population
      ages, but its rapid diagnosis and phenotype identification remain challenging. We
      sought to determine whether acoustic cardiography can accurately identify HF and
      its phenotypes. METHODS: Three cohorts of patients were studied [94 with
      hypertension, 109 with HF and normal ejection fraction (HFNEF, EF >= 50%) and 89
      with HF and reduced ejection fraction (HFREF, EF<50%)]. All participants received
      acoustic cardiography and echocardiography examinations. Acoustic cardiographic
      parameters included S3 score (probability that the third heart sound exists),
      electromechanical activation time (EMAT, interval from Q wave to the first heart
      sound; EMAT/RR is EMAT normalized by heart rate), and systolic dysfunction index
      (SDI, a combination of EMAT/RR, S3 score, QRS duration and QR interval). Receiver
      operative characteristic curves were used to determine diagnostic utility of
      acoustic cardiography. RESULTS: EMAT/RR significantly differentiated HFNEF from
      hypertension (area under curve [AUC], 0.83; 95% confidence interval [CI], 0.77
      0.89) with an EMAT/RR>11.54% yielded 55% sensitivity and 90% specificity.
      Similarly, an echo-measured E/e'>15 yielded 55% sensitivity, 90% specificity and
      0.84 AUC in detecting HFNEF. Whereas SDI out-performed the other acoustic
      cardiographic parameters in differentiating HFREF from HFNEF (AUC, 0.81; 95% CI,
      0.75-0.87), and an SDI>5.43 yielded 53% sensitivity and 91% specificity. The E/e'
      ratio had a similar diagnostic performance. CONCLUSIONS: Our study demonstrates
      that this bedside technology may be helpful in identifying HF and its phenotypes,
      especially when echocardiography is not immediately available.

PMID- 22456264
TI  - Transient CPEB dimerization and translational control.
AB  - During oocyte development, the cytoplasmic polyadenylation element-binding
      protein (CPEB) nucleates a set of factors on mRNA that controls cytoplasmic
      polyadenylation and translation. The regulation of polyadenylation is mediated in
      part through serial phosphorylations of CPEB, which control both the dynamic
      integrity of the cytoplasmic polyadenylation apparatus and CPEB stability, events
      necessary for meiotic progression. Because the precise stoichiometry between CPEB
      and CPE-containing RNA is responsible for the temporal order of mRNA
      polyadenylation during meiosis, we hypothesized that, if CPEB production exceeded
      the amount required to bind mRNA, the excess would be sequestered in an inactive
      form. One attractive possibility for the sequestration is protein dimerization.
      We demonstrate that not only does CPEB form a dimer, but dimerization requires
      its RNA-binding domains. Dimer formation prevents CPEB from being UV cross-linked
      to RNA, which establishes a second pool of CPEB that is inert for polyadenylation
      and translational control. During oocyte maturation, the dimers are degraded much
      more rapidly than the CPEB monomers, due to their greater affinity for polo-like
      kinase 1 (plx1) and the ubiquitin E3 ligase beta-TrCP. Because dimeric CPEB also
      binds cytoplasmic polyadenylation factors with greater affinity than monomeric
      CPEB, it may act as a hub or reservoir for the polyadenylation machinery. We
      propose that the balance between CPEB and its target mRNAs is maintained by CPEB
      dimerization, which inactivates spare proteins and prevents them from inducing
      polyadenylation of RNAs with low affinity binding sites. In addition, the dimers
      might serve as molecular hubs that release polyadenylation factors for
      translational activation upon CPEB dimer destruction.

PMID- 22456265
TI  - Doing it in reverse: 3'-to-5' polymerization by the Thg1 superfamily.
AB  - The tRNA(His) guanylyltransferase (Thg1) family of enzymes comprises members from
      all three domains of life (Eucarya, Bacteria, Archaea). Although the initial
      activity associated with Thg1 enzymes was a single 3'-to-5' nucleotide addition
      reaction that specifies tRNA(His) identity in eukaryotes, the discovery of a
      generalized base pair-dependent 3'-to-5' polymerase reaction greatly expanded the
      scope of Thg1 family-catalyzed reactions to include tRNA repair and editing
      activities in bacteria, archaea, and organelles. While the identification of the
      3'-to-5' polymerase activity associated with Thg1 enzymes is relatively recent,
      the roots of this discovery and its likely physiological relevance were described
      ~ 30 yr ago. Here we review recent advances toward understanding diverse Thg1
      family enzyme functions and mechanisms. We also discuss possible evolutionary
      origins of Thg1 family-catalyzed 3'-to-5' addition activities and their
      implications for the currently observed phylogenetic distribution of Thg1-related
      enzymes in biology.

PMID- 22456267
TI  - Epigenetic aspects on therapy development for gastroenteropancreatic
      neuroendocrine tumors.
AB  - The understanding of epigenetic modifications in gastroenteropancreatic
      neuroendocrine tumors is a novel and still small field. Activation of the insulin
      like growth factor 2 gene locus by loss of imprinting is a classical epigenetic
      alteration frequently observed in insulinoma. Inactivation of the MEN1 gene,
      commonly involved in endocrine pancreatic tumors, impairs the association with
      mixed lineage leukemia involved in histone H3K4me3 methylation. In addition,
      promising effects on tumor phenotypes such as growth, apoptosis, cell cycle
      arrest, and expression of neuroendocrine markers have been obtained in vitro for
      inhibitors of DNA methyltransferase (azacytidine) and histone deacetylation
      (butyrate, valproic acid, trichostatin A and MS-275). The frequent need for
      complementary treatments in addition to surgery in this tumor entity supports
      further efforts in the development and application of drugs acting at general as
      well as more specific epigenetic alterations.

PMID- 22456266
TI  - The cardiotonic steroid digitoxin regulates alternative splicing through
      depletion of the splicing factors SRSF3 and TRA2B.
AB  - Modulation of alternative pre-mRNA splicing is a potential approach to
      therapeutic targeting for a variety of human diseases. We investigated the
      mechanism by which digitoxin, a member of the cardiotonic steroid class of drugs,
      regulates alternative splicing. Transcriptome-wide analysis identified a large
      set of alternative splicing events that change after digitoxin treatment. Within
      and adjacent to these regulated exons, we identified enrichment of potential
      binding sites for the splicing factors SRp20 (SRSF3/SFRS3) and Tra2-beta
      (SFRS10/TRA2B). We further find that both of these proteins are depleted from
      cells by digitoxin treatment. Characterization of SRp20 and Tra2-beta splicing
      targets revealed that many, but not all, digitoxin-induced splicing changes can
      be attributed to the depletion of one or both of these factors. Re-expression of
      SRp20 or Tra2-beta after digitoxin treatment restores normal splicing of their
      targets, indicating that the digitoxin effect is directly due to these factors.
      These results demonstrate that cardiotonic steroids, long prescribed in the
      clinical treatment of heart failure, have broad effects on the cellular
      transcriptome through these and likely other RNA binding proteins. The approach
      described here can be used to identify targets of other potential therapeutics
      that act as alternative splicing modulators.

PMID- 22456268
TI  - Open access and optometry and vision science.

PMID- 22456269
TI  - Therapeutics and the profession of optometry-a look back.

PMID- 22456272
TI  - Opticochiasmatic apoplexy in a five-year-old.
AB  - A 5-year-old female presented to the emergency department with a 24-hour history
      of nausea, vomiting and mental status changes. Imaging demonstrated hemorrhage
      from a suprasellar mass consistent with an optic nerve glioma. The patient was
      taken to surgery for an open biopsy and hematoma evacuation. Pathology revealed a
      grade 3 fibrillary astrocytoma. She was subsequently treated with carboplatin and
      vincristine and is now 2 years out without evidence of recurrence. Apoplexy is a
      rare presentation for an optic pathway glioma. To the authors' knowledge, this is
      the first reported case in the pediatric population. Clinical presentation
      appears similar to the symptoms observed in pituitary apoplexy. Timely surgery
      should be directed at obtaining diagnostic tissue, prevention of long-term
      nervous system damage and evacuation of the hematoma where feasible.

PMID- 22456273
TI  - Using amphiphilic nanostructures to enable long-range ensemble coalescence and
      surface rejuvenation in dropwise condensation.
AB  - Controlling coalescence events in a heterogeneous ensemble of condensing droplets
      on a surface is an outstanding fundamental challenge in surface and interfacial
      sciences, with a broad practical importance in applications ranging from thermal
      management of high-performance electronic devices to moisture management in high
      humidity environments. Nature-inspired superhydrophobic surfaces have been
      actively explored to enhance heat and mass transfer rates by achieving favorable
      dynamics during dropwise condensation; however, the effectiveness of such
      chemically homogeneous surfaces has been limited because condensing droplets tend
      to form as pinned Wenzel drops rather than mobile Cassie ones. Here, we introduce
      an amphiphilic nanostructured surface, consisting of a hydrophilic base with
      hydrophobic tips, which promotes the periodic regeneration of nucleation sites
      for small droplets, thus rendering the surface self-rejuvenating. This unique
      amphiphilic nanointerface generates an arrangement of condensed Wenzel droplets
      that are fluidically linked by a wetted sublayer, promoting previously unobserved
      coalescence events where numerous droplets simultaneously merge, without direct
      contact. Such ensemble coalescences rapidly create fresh nucleation sites,
      thereby shifting the overall population toward smaller droplets and enhancing the
      rates of mass and heat transfer during condensation.

PMID- 22456274
TI  - Functionalization of organic membranes by polyelectrolyte multilayer assemblies:
      application to the removal of copper ions from aqueous solutions.
AB  - The functionalization of an organic polyethersulfone membrane (PES) was performed
      by alternating deposition of poly(allylamine hydrochloride) (PAH) and poly(sodium
      4-styrene sulfonate) (PSS), leading to the formation of a polyelectrolyte
      multilayer film (PEM). The resulting assembly was characterized by tangential
      streaming potential measurements to determine the charge of the modified
      membranes as a function of the polyelectrolyte solution concentration and as a
      function of the immersion time of the membrane in the polyelectrolyte solutions.
      Then, the modified membranes were used to perform the ultrafiltration of aqueous
      solutions containing copper(II) ions. Different operating conditions were tested
      including: polyelectrolyte concentration, polyelectrolyte nature, thickness of
      the PEM film or pH of the Cu(2+) solutions. These filtration experiments
      demonstrated that it was possible to obtain a satisfactory retention of the
      copper ions (88%), thus proving that this type of assembly can be useful for the
      removal of copper ions from contaminated aqueous solutions.

PMID- 22456275
TI  - Electrospinning preparation, characterization and magnetic properties of cobalt
      nickel ferrite (Co(1-x)Ni(x)Fe2)O4) nanofibers.
AB  - Uniform Co(1-)(x)Ni(x)Fe(2)O(4) (x=0.0, 0.2, 0.4, 0.6, 0.8 and 1.0) nanofibers
      with average diameter of 110 nm and length up to several millimeters were
      prepared by calcination of electrospun precursor nanofibers containing polymer
      and inorganic salts. The as-spun and calcined nanofibers were characterized in
      detail by TG-DTA, XRD, FE-SEM, TEM, SAED and VSM, respectively. The effect of
      composition of the nanofibers on the structure and magnetic properties were
      investigated. The nanofibers are formed through assembling magnetic nanoparticles
      with poly(vinyl pyrrolidone) as the structure-directing template. The structural
      characteristics and magnetic properties of the resultant nanofibers vary with
      chemical composition and can be tuned by adjusting the Co/Ni ratio. Both lattice
      parameter and particle size decrease gradually with increasing nickel
      concentration. The saturation magnetization and coercivity lie in the range 29.3
      56.4 emu/g and 210-1255 Oe, respectively, and both show a monotonously decreasing
      behavior with the increase in nickel concentration. Such changes in magnetic
      properties can mainly be attributed to the lower magnetocrystalline anisotropy
      and the smaller magnetic moment of Ni(2+) ions compared to Co(2+) ions.
      Furthermore, the coercivity of Co-Ni ferrite nanofibers is found to be superior
      to that of the corresponding nanoparticle counterparts, presumably due to their
      large shape anisotropy. These novel one-dimensional Co-Ni ferrite magnetic
      nanofibers can potentially be used in micro-/nanoelectronic devices, microwave
      absorbers and sensing devices.

PMID- 22456276
TI  - Precipitation of silver/palladium alloy platelets from homogeneous solutions.
AB  - Dispersed silver/palladium (Ag/Pd) nanoplatelets were prepared by delivering in
      parallel solutions of mixed metal nitrates and L-ascorbic acid into a nitric acid
      solution containing Arabic gum. The shape and size of bimetallic nanoparticles
      varied with the silver/palladium weight ratio and the concentration of nitric
      acid. The optimum conditions for platelets formation were a palladium content of
      ~2.0 wt.% and nitric acid concentrations above 1.0 mol dm(-3). The data presented
      show that both parameters play a critical role in the nucleation and growth of
      AgPd particles. A mechanism explaining the formation of the bimetallic
      nanoplatelets is proposed.

PMID- 22456277
TI  - Vav1 GEF activity is required for T cell mediated allograft rejection.
AB  - The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of
      the T cell receptor and has been identified as a key factor for T cell activation
      in the context of allograft rejection. Vav1 has been shown to transduce signals
      both dependent and independent of its GEF function. The most promising approach
      to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF
      function. However, the contribution of Vav1 GEF activity for allogeneic T cell
      activation has not been clarified yet. To address this question, we used knock-in
      mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF
      independent functions. T cells from these mice showed strongly reduced
      proliferation and activation in response to allogeneic stimulation. Furthermore,
      lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in
      a systemic graft-versus-host model. In a cardiac transplantation model, mice with
      disrupted Vav1 GEF activity show prolonged allograft survival. These findings
      demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell
      activation and graft rejection suggesting that disruption of Vav1 GEF activity
      alone is sufficient to induce significant immunosuppression.

PMID- 22456278
TI  - Evidence for an intronic cis-regulatory element within CD69 gene.
AB  - CD69 is one of the earliest proteins expressed after leukocyte activation and its
      engagement is essential in the control of innate and adaptive immune responses.
      Inducible CD69 expression is strongly controlled at the transcriptional level.
      The molecular basis for developmental- and stage-specific regulation in T cells
      is beginning to be elucidated while it remains largely unknown in the rest of
      immune cells. DNase I hypersensitivity experiments in lymphocytes identified a
      novel hypersensitive region within mouse and human intron I, which was inducible
      upon stimulation. In silico analysis of CD69 gene revealed that this open
      chromatin region was present in different cell types and was associated with
      positioned nucleosomes. Analysis of histone post-translational modifications of
      intron I indicated that acetylation and lysine 4 dimethylation of histone H3 were
      dynamically regulated during thymocyte development and were constitutively high
      in resting and stimulated mature T lymphocytes. Thus, we provide evidence for the
      existence of a cis-acting element in intron I that is more accessible to DNase I
      digestion and that it is developmentally regulated at the chromatin level.

PMID- 22456279
TI  - The effect of allogenetic bone marrow-derived mesenchymal stem cell
      transplantation on lung aquaporin-1 and -5 in a rat model of severe acute
      pancreatitis.
AB  - BACKGROUND/AIMS: We aimed to determine the effect of transplantation on post- ALI
      (acute lung injury) edema in severe acute pancreatitis (SAP) and the expression
      levels of aquaporins -1 and -5 (AQP-1 and -5). METHODOLOGY: Sprague-Dawley (SD)
      rats were randomized into control-SAP and BMSCs-SAP groups. SAP model was
      prepared through retrograde injection of 5% taurocholic acid. BMSCs were isolated
      from the bone marrow of SD rats. We examined SAP rats for levels of IL-1beta and
      TNF-a, and for AQP-1 and -5 expression in lung tissues at 6 and 12 hours.
      RESULTS: The levels of IL-1beta and TNF-a in BMSC-SAP rats were lower than in
      control-SAP rats (both, p<0.001). Real-time RT-PCR analysis showed that AQP-1
      mRNA expression in BMSC-SAP rats was higher than that in control-SAP rats
      (p=0.005 and p<0.001), and AQP-5 mRNA expression in BMSC-SAP rats was also higher
      than that in control-SAP rats (p=0.031 and p=0.006). Western blotting analysis
      showed that AQP-1 and AQP-5 protein levels at 12h were significantly higher in
      BMSC-SAP rats than in control-SAP rats (p<0.001). CONCLUSIONS: Allogenic BMSC
      transplantation can protect against ALI in a rat SAP model and can also regulate
      the expression levels of AQP-1 and -5 by inhibiting IL-1beta and TNF-a.

PMID- 22456280
TI  - Comparison of preoperative images with gross and histopathological findings of
      liver slices in patients with liver metastases from colorectal cancer after
      chemotherapy.
AB  - BACKGROUND/AIMS: Since there is a difference in the slice thickness between
      preoperative images of liver metastases (1-3mm slices) and surgical liver
      pathology specimens (5mm slices), micrometastases may not be detected in these
      specimens. In addition, the accuracy of preoperative imaging for the detection of
      metastases degenerated by chemotherapy is unclear. METHODOLOGY: Five patients
      with liver metastases from colorectal cancer who had received adjuvant
      chemotherapy and undergone hepatectomy were included. The whole resected liver
      was sliced at approximately 1mm intervals and the slices were examined carefully
      for gross lesions. The preoperative CT and EOB-MRI findings of each lesion were
      compared with gross and histopathological findings. RESULTS: The accuracy of EOB
      MRI was higher than that of CT for the detection of liver metastases. The number
      of lesions detected on EOB-MRI was in agreement with that of histopathologically
      proven liver metastases in 4 of the 5 patients. All lesions that were grossly
      identified but turned out to be non-neoplastic were regenerative nodules
      associated with drug-induced liver injury or lobular nodules associated with
      marked fatty change, measuring about 1mm in diameter. CONCLUSIONS: EOB-MRI was
      the most accurate method for the preoperative detection of liver metastases,
      enabling the visualization of almost all liver metastases.

PMID- 22456281
TI  - Combined laparoendoscopic single-site surgery: initial experience of a single
      center.
AB  - BACKGROUND/AIMS: This study reports the initial experience with combined
      laparoendoscopic single-site surgery (LESS) referring to cholecystectomy,
      appendectomy, oophorocystectomy and liver cyst and renal cyst fenestration and
      explore the feasibility and safety of combined LESS. METHODOLOGY: From October
      2008 to May 2011 selective 24 patients underwent combined LESS in our center. The
      single incision in umbilicus was about 2cm. All the operations were performed by
      the same surgical team and used conventional rigid instruments. RESULTS: In 24
      patients, combined laparoendoscopic single-site cholecystectomy and appendectomy
      were performed in 17 cases, combined cholecystectomy and liver cyst fenestration
      in 5 cases and combined cholecystectomy and oophorocystectomy in 2 cases. Twenty
      one patients were successfully operated and the other 3 were converted to
      conventional laparoscopic surgery because of separating Calot's triangle
      difficulty. The mean operating time was 87.3 minutes. One urinary retention
      (4.2%) and one fat liquefaction in abdominal incision (4.2%) occurred and were
      cured conservatively. There was no mortality in the study. CONCLUSIONS: Combined
      laparoendoscopic single-site surgery is safe, feasible, minimally invasive and
      cosmetic technique but is more difficult than conventional laparoscopic surgery.
      It is a reasonable alternative to be performed in selective patients by
      experienced laparoscopic surgeons.

PMID- 22456282
TI  - Fgl2 prothrombinase is involved in severe acute pancreatitis-associated liver
      injury.
AB  - BACKGROUND/AIMS: Severe acute pancreatitis (SAP)-associated liver injury is
      systematically one of main pathophysiological events due to SAP development. The
      aim of the study was to investigate whether fgl2 prothrombinase is involved in
      SAP-associated liver injury. METHODOLOGY: Microthrombosis in the liver of rats
      with SAP was observed by Masson staining. Fgl2 prothrombinase expression in the
      liver of rats with SAP was analyzed by real-time PCR and immunohistochemistry
      methods. RESULTS: Fgl2 prothrombinase gene and protein expression in SAP group
      were significantly up-regulated compared to sham-operation (SO) group.
      Immunohistochemistry staining showed that fgl2 prothrombinase was localized
      speci?cally to the endothelial cells of intrahepatic veins and hepatic sinusoids.
      Furthermore, Masson staining demonstrated that the proportion of hepatic
      microthrombotic capillaries in SAP group were evidently increasing in comparison
      to SO group and closely correlated with fgl2 expression (r=0.948, p<0.01 ). In
      addition, there was a positive correlation between fgl2 expression and the
      severity of hepatocellular injury as indicated by hepatic pathological grade
      (r=0.704, p<0.01). CONCLUSIONS: Fgl2 prothrombinase may contribute to
      microthrombosis in SAP-associated liver injury, thus resulting in hepatic
      microcirculatory disturbance and measurement of fgl2 may be used as a helpful
      biomarker in the prognosis of the severity of hepatic pathological injury in SAP.

PMID- 22456283
TI  - Therapeutic plasma exchange in systemic vasculitis:  an update on indications and
      results.
AB  - PURPOSE OF REVIEW: Therapeutic plasma exchange has been long proposed as a
      potentially useful modality to treat several systemic vasculitis conditions. This
      review summarizes the available evidence for the effectiveness of plasma exchange
      in systemic vasculitis. RECENT FINDINGS: Therapy with plasma exchange, most often
      combined with immunosuppressive agents, has been found effective for
      antiglomerular basement membrane disease, antineutrophil cytoplasmic antibody
      associated vasculitis (AAV), Henoch-Schonlein purpura, cryoglobulinemic
      vasculitis, hepatitis B virus-associated polyarteritis nodosa and Kawasaki
      disease. The most common indications are life-threatening or organ function
      threatening manifestations, particularly advanced renal dysfunction and disease
      refractory to traditional therapy. Thus, most of the available evidence favoring
      plasma exchange in these circumstances is from small observational studies or
      expert consensus. Recent advances in findings include results strengthening the
      notion of a small beneficial effect on preserving renal function with adjunct
      plasma exchange therapy in AAV with renal failure and observational data
      suggesting plasma exchange as a promising effective salvage option for children
      with Kawasaki disease not responding to standard therapy with intravenous
      immunoglobulins. SUMMARY: Evidence from case reports and case series and a few
      randomized controlled trials continues to support plasma exchange as a major
      rescue-treatment modality for several systemic vasculitis diseases. These studies
      offer some guidance for use of plasma exchange in systemic vasculitis, but
      additional data from controlled trials are needed for more accurate assessment of
      the indications, practical modalities, benefits and shortcomings of this
      treatment approach.

PMID- 22456284
TI  - Current world literature.

PMID- 22456286
TI  - Phosphine-boronates: efficient bifunctional organocatalysts for Michael addition.
AB  - Phosphine-boronates R(2)P(o-C(6)H(4))B(OR')(2) have been evaluated as
      bifunctional organocatalysts for the Michael addition of malonate pronucleophiles
      to methylvinylketone. The presence of the Lewis acidic boron center adjacent to
      phosphorus significantly improves catalytic performance. Isolation and complete
      characterization of a key intermediate, namely a beta-phosphonium enolate,
      substantiate the role of the Lewis acidic moiety in the catalytic process.

PMID- 22456287
TI  - [EndoBarrier for counteracting obesity and metabolic syndrome].
AB  - The prevalence of obesity is increasing worldwide. Its primary treatment consists
      of lifestyle changes. In severely obese (BMI > 40 kg/m2 or >= 35 kg/m2 with
      comorbidity) patients though, bariatric surgery has been found to be the only way
      to achieve permanent weight loss. Operations such as the placement of a gastric
      band or a gastric bypass can, however, lead to complications and necessitate
      secondary interventions. In search of less invasive treatments, placement of the
      EndoBarrier duodenal jejunal bypass liner appears to be a promising, safe and
      effective method for facilitating weight loss. The EndoBarrier is a plastic
      flexible tube which is gastroscopically placed in the duodenal bulb, directly
      behind the pylorus. It extends from the duodenum to the proximal jejunum. Recent
      studies have demonstrated significant weight reduction in comparison to control
      diet patients. Concomitant positive effects on cardiovascular risk factors
      including diabetes type 2 were observed. A multicentre trial is currently being
      executed in order to unravel the mechanism behind these effects.

PMID- 22456288
TI  - [Bariatric surgery with an adjustable gastric band; long-term follow-up of the
      first 30 patients in the Netherlands].
AB  - OBJECTIVE: Evaluation of the long-term results of bariatric surgery with an
      adjustable gastric band for the treatment of morbid obesity. DESIGN:
      Retrospective, descriptive. METHOD: From September 1991-September 1993, 30
      patients (6 males, 24 females) received an adjustable gastric band because of
      morbid obesity, being the first group in the Netherlands. The long-term data on
      these patients: weight loss, band adjustments, complications, reoperations and
      patient satisfaction, were collected using a medical record survey and a
      questionnaire and then analysed. RESULTS: Before the operation, the mean BMI was
      42.5 kg/m2 (SD: 5.7) and the mean excess body weight was 50.8 kg (SD: 16.7). The
      mean follow-up time for all patients was 15.3 years (SD: 5.4) and for the
      responders to the questionnaire, 17.7 years (SD: 0.7); three patients died during
      follow-up. After surgery, the mean BMI was reduced to 34.7 kg/m2 (SD: 6.4). The
      mean excess body weight loss of the entire group was 38.1% (SD: 67.8) and of the
      patients who still had a gastric band in situ, 27.9% (SD: 67.4). In 15 patients,
      the gastric band reservoir was replaced at least once. The gastric band was
      replaced in 18 patients due to complications and eventually permanently removed
      in 6 patients. Of the respondents, 62% were satisfied with the weight loss and
      52% were satisfied with regard to possible side effects and complications.
      CONCLUSION: The treatment of morbid obesity with an adjustable gastric band in
      this very first group of patients has resulted in substantial weight loss, but
      also a high rate of complications and reoperations. Treatment of these kinds of
      complications is an important aspect of bariatric surgery today. The efficacy of
      gastric banding is therefore currently under debate.

PMID- 22456289
TI  - [Myocardial infarction without ECG abnormalities: consider occlusion of the
      circumflex coronary artery].
AB  - BACKGROUND: In patients with posterior wall myocardial infarction due to an
      occlusion of the circumflex coronary artery, a standard ECG does not show ST
      elevation in half of the cases. CASE DESCRIPTION: Two male patients aged 55 and
      52 years were admitted to our hospital because of chest pain and suspected
      myocardial infarction. In both patients, standard electrocardiograms (ECGs)
      showed no signs of ischemia. Pharmacological treatment with acetylsalicylic acid,
      heparin, clopidogrel and nitroglycerin did not relieve their chest pain.
      Echocardiography and the posterior ECG leads revealed signs of ischemia in the
      posterior wall. Coronary angiography revealed that the circumflex coronary artery
      was totally occluded in both patients. They were treated successfully by
      percutaneous coronary intervention. CONCLUSION: In approximately 50% of patients
      with myocardial infarction due to occlusion of the circumflex coronary artery, ST
      segment elevation is limited or absent on the standard 12-lead ECG. These two
      cases emphasise that posterior ECG and echocardiography are valuable tools for
      detecting posterior wall infarction.

PMID- 22456290
TI  - [Bilateral Achilles tendon rupture following levofloxacin and glucocorticoid
      use].
AB  - The combination of fluorquinolones and glucocorticoids leads to a high risk of
      tendon rupture. Especially the Achilles tendon is at risk. We present a report of
      a 65-year-old woman with a bilateral Achilles tendon rupture following use of
      levofloxacin and corticosteroids for pneumonia. Symptoms of the tendons in
      patients using glucocorticoids and fluorquinolones should be evaluated. The
      physician should be aware of the high risk of an Achilles tendon rupture,
      particularly in older patients using this combination.

PMID- 22456291
TI  - [Bias in observational research: 'confounding'].
AB  - Confounding is an important and common issue in observational (non-randomized)
      research on the effects of pharmaceuticals or exposure to etiologic factors
      (determinants). Confounding is present when a third factor, related to both the
      determinant and the outcome, distorts the causal relation between these two.
      There are different methods to control for confounding. The most commonly used
      are restriction, stratification, multivariable regression models, and propensity
      score methods. With these methods it is only possible to control for variables
      for which data is known: measured confounders. Research in the area of
      confounding is currently directed at the incorporation of external knowledge on
      unmeasured confounders, the evaluation of instrumental variables, and the impact
      of time-dependent confounding.

PMID- 22456292
TI  - [Endobarrier: a unique but still premature concept].
AB  - The EndoBarrier, an endoscopically delivered duodeno-jejunal bypass device, is a
      unique concept that starts to ameliorate the symptoms of diabetes mellitus type
      2, soon after positioning. Weight-loss results are moderate, with 85% of patients
      showing a more than 10% excess weight loss in the 12 weeks preoperatively.
      Sufficient implant training is required, but problems can still occur, e.g., due
      to a short duodenal bulb length. The stability of the anchors and the
      tolerability of the device still leave much to be desired. In 25% of patients the
      EndoBarrier is explanted early, because of migration, physical symptoms,
      gastrointestinal haemorrhage, rotation and obstruction. Only seven studies on the
      EndoBarrier are available and these are mostly small in size, short-term and with
      limited follow-up, and many questions regarding the safety and long-term effects
      of the device remain. This calls for a large, long-term, randomised, placebo
      controlled, double-blind trial. Lessons should have been learned from the
      disastrous results with intragastric balloon implantation before commercialising
      another such product.

PMID- 22456293
TI  - Methylation and expression analyses of the 7q autism susceptibility locus genes
      MEST , COPG2, and TSGA14 in human and anthropoid primate cortices.
AB  - The autism susceptibility locus on human chromosome 7q32 contains the maternally
      imprinted MEST and the non-imprinted COPG2 and TSGA14 genes. Autism is a disorder
      of the 'social brain' that has been proposed to be due to an overbalance of
      paternally expressed genes. To study regulation of the 7q32 locus during
      anthropoid primate evolution, we analyzed the methylation and expression patterns
      of MEST, COPG2, and TSGA14 in human, chimpanzee, Old World monkey (baboon and
      rhesus macaque), and New World monkey (marmoset) cortices. In all human and
      anthropoid primate cortices, the MEST promoter was hemimethylated, as expected
      for a differentially methylated imprinting control region, whereas the COPG2 and
      TSGA14 promoters were completely demethylated, typical for transcriptionally
      active non-imprinted genes. The MEST gene also showed comparable mRNA expression
      levels in all analyzed species. In contrast, COPG2 expression was downregulated
      in the human cortex compared to chimpanzee, Old and New World monkeys. TSGA14
      either showed no differential regulation in the human brain compared to
      chimpanzee and marmoset or a slight upregulation compared to baboon. The human
      specific downregulation supports a role for COPG2 in the development of a 'social
      brain'. Promoter methylation patterns appear to be more stable during evolution
      than gene expression patterns, suggesting that other mechanisms may be more
      important for inter-primate differences in gene expression.

PMID- 22456294
TI  - Effects of meal timing relative to dosing on the pharmacokinetics and
      pharmacodynamics of vildagliptin in Japanese patients with Type 2 diabetes.
AB  - OBJECTIVE: To assess the effects of meal timing on the pharmacokinetics and
      pharmacodynamics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin in
      Japanese patients with Type 2 diabetes. METHODS: In this open-label, single
      center crossover study, 12 Japanese patients with Type 2 diabetes were randomized
      to twice-daily vildagliptin 50 mg, administered 30 min before or immediately
      before breakfast and dinner for 7 days. After a 7-day washout period, patients
      received the other regimen. Blood samples were collected for the determination of
      vildagliptin, DPP-4, glucagon-like peptide-1 (GLP-1) and glucose. RESULTS:
      Vildagliptin absorption appeared slower when administered 30 min before rather
      than immediately before meals (tmax absolute range: 1.00 - 2.00 h vs. 0.33 - 1.58
      h). Vildagliptin Cmax and AUC0-8 h were essentially the same irrespective of meal
      timing (geometric mean ratio: Cmax 1.08 (90% CI; 0.92 - 1.26); AUC0-8 h 0.97 (90%
      CI; 0.91 - 1.05)). Meal timing did not affect pharmacodynamics; complete DPP-4
      inhibition (> 90%) was sustained for 8 h post-dose, and plasma active glucagon
      like peptide-1 levels increased 2 - 3-fold from baseline. Fasting plasma glucose
      (FPG) and postprandial plasma glucose (PPPG) reductions from baseline did not
      differ significantly with meal timing (30 min before vs. immediately before: FPG,
      -8.9 vs. -5.8 mg/dl; adjusted AUE0-4 h, -67.0 vs. -51.0 mg*h/dl). Vildagliptin
      was well tolerated. CONCLUSIONS: Dosing 30 min or immediately before meals did
      not affect vildagliptin pharmacokinetics or pharmacodynamics in Japanese patients
      with Type 2 diabetes.

PMID- 22456295
TI  - No clinically relevant drug-drug interactions when dalcetrapib is co-administered
      with a monophasic oral contraceptive (Microgynon(r) 30).
AB  - Dalcetrapib, a cholesteryl ester transfer protein modulator, under development to
      increase high-density lipoprotein cholesterol and potentially decrease
      cardiovascular risk, will potentially be co-prescribed to women on oral
      contraceptive (OC). OBJECTIVE: Assess the effect of dalcetrapib on the
      pharmacokinetics and ability to suppress ovulation of Microgynon(r) 30, a
      representative monophasic OC. MATERIALS AND METHODS: A single-center, randomized,
      open-label, two-period crossover study in healthy women receiving monophasic OC.
      Subjects received Microgynon(r) 30 (ethinylestradiol 0.03 mg/levonorgestrel 0.15
      mg) once daily for 21 days followed by 7 treatment-free days (run-in period),
      then were randomized to Microgynon(r) 30 daily for 21 days with or without
      dalcetrapib 900 mg daily for Day 1 - 14. Plasma ethinylestradiol and
      levonorgestrel were measured on Day 14, and luteinizing hormone, follicle
      stimulating hormone, progesterone and estrogen from Day 11 - 14. The primary
      endpoint plasma exposure (AUC0-24 and Cmax) on Day 14 was evaluated for
      ethinylestradiol and levonorgestrel. Safety was monitored throughout. RESULTS: 30
      subjects were randomized. The exposure of ethinylestradiol and levonorgestrel was
      similar when Microgynon(r) 30 was administered with or without dalcetrapib; for
      ethinylestradiol the geometric mean ratio %, (90% confidence interval (CI)) for
      AUC0-24 and Cmax were 92 (86 - 98) and 105 (95 - 115) and for levonorgestrel 92
      (88 - 96) and 93 (87 - 99), respectively. Concentrations of luteinizing hormone,
      follicle stimulating hormone, estrogen and progesterone were comparable between
      treatments. CONCLUSIONS: Dalcetrapib has no clinically relevant effect on the
      pharmacokinetics of ethinylestradiol and levonorgestrel. Contraceptive efficacy
      of Microgynon(r) 30 is not anticipated to be compromised by co-administration of
      dalcetrapib.

PMID- 22456296
TI  - A retrospective database analysis on persistence with inhaled corticosteroid
      therapy: comparison of two dry powder inhalers during asthma treatment in
      Germany.
AB  - BACKGROUND: Asthma is one of the most common chronic diseases worldwide. Patient
      persistence with treatment is essential to achieve sufficient outcomes, in
      particular to avoid exacerbations. OBJECTIVE: To investigate inhaled
      corticosteroid (ICS) therapy with two different inhalers (Novolizer(r) and
      Turbuhaler(r)) by comparing persistence, concomitant use of additional asthma
      medication and occurrence of exacerbations in real life. STUDY DESIGN: A
      retrospective analysis of prescription data from outpatient treatment was
      performed using the IMS Disease Analyzer. It provides longitudinal anonymized
      patient data from ~ 3,000 office-based physicians in Germany. Treatment
      persistence of asthma patients (ICD 10 code: J45) using 200 MUg budesonide either
      via Novopulmon(r)/Budecort(r) (Novolizer group = NOV) or Pulmicort(r) (Turbuhaler
      group = TUR) was compared. Eligible patients hadthe first prescription of ICS
      medication (index day) between June 2001 and September 2007 and a data history
      available for at least twelve months before and after the index day. RESULTS:
      Analysis of 1,780 NOV and 664 TUR patients revealed that 1 year after index day,
      89% NOV patients remained on their ICS compared to 85% TUR patients. NOV patients
      changed significantly less often and later to another ICS (p = 0.0108; log-rank
      test). Significantly fewer NOV patients switched temporarily or permanently to
      another ICS during the observation time (NOV group: 14.7%; TUR group: 20.8%; p =
      0.0002, log-rank test). On average, NOV and TUR patients received comparable
      prescriptions of short acting medication (NOV more SABA, TUR more formoterol).
      There was a trend towards fewer prescriptions of systemic corticosteroids in NOV
      patients. CONCLUSIONS: Our results suggest better therapy persistence with NOV
      compared to TUR during asthma treatment in Germany. This can be a marker of
      better compliance and may contribute to prevent exacerbations. However, the
      number of exacerbations per patient year in the NOV group (0.12) compared to the
      TUR group (0.18) was not statically significantly lower (p = 0.4096).

PMID- 22456297
TI  - Relationship between serum allantoin and urate in healthy subjects and effects of
      benzbromarone in gout patients.
AB  - BACKGROUND: Although hyperuricemia is suggested to increase allantoin production
      in both pro- and antioxidant manners, it remains undetermined whether it
      increases the serum concentration of allantoin. In addition, since uric acid has
      both pro- and antioxidant actions, a decrease in the serum concentration of uric
      acid may have an effect on the pro-oxidant-antioxidant balance. METHODS: To
      examine whether serum allantoin is correlated with serum urate, we measured those
      levels as well as other parameters in 63 healthy subjects. In addition, to
      determine whether serum allantoin is correlated with reactive oxygen species
      (ROS) biomarkers, we measured 8-hydroxy deoxyguanosine and 15-F2t-isoprostane,
      markers of ROS, in urine samples from 30 gout patients before and 1 year after
      benzbromarone treatment (50 mg/d). RESULTS: The serum concentration of allantoin
      was correlated with that of urate in healthy subjects (R = 0.27, p < 0.05).
      Benzbromarone treatment in the patients decreased the concentrations of allantoin
      and urate in serum by 17% (p < 0.05) and 49% (p < 0.05), respectively, and the
      benzbromarone-induced change in serum allantoin was correlated with that in serum
      urate (R = 0.39, p < 0.05). However, benzbromarone treatment did not change the
      ratios of 8-hydroxydeoxyguanosine/creatinine or 15-F2t-isoprostane/creatinine in
      urine. CONCLUSIONS: Our findings suggest that hyperuricemia contributes to an
      increase in serum concentration of allantoin, though they do not indicate that
      hyperuricemia is a major factor for controlling oxidative stress in vivo.

PMID- 22456298
TI  - Population pharmacokinetics of mycophenolate mofetil in Thai lupus nephritis
      patients.
AB  - OBJECTIVE: Mycophenolic acid (MPA) has become the first-line drug therapy for
      proliferative lupus nephritis, a common and serious complication of systemic
      lupus erythematosus. Although a sufficient MPA exposure is required, a high
      interindividual variability in the pharmacokinetics of MPA has been observed. The
      knowledge of MPA pharmacokinetics in lupus nephritis patients is limited,
      especially in Asian patients. This study aimed to develop a population
      pharmacokinetic model for MPA and determine the population pharmacokinetic
      parameters and their interindividual variability in Thai patients with lupus
      nephritis. METHODS: A total of 112 MPA plasma concentrations from 14 adult lupus
      nephritis patients (International Society of Nephrology/Renal Pathology Society
      Class III/IV) receiving mycophenolate mofetil were included in this study. The
      data was analyzed using NONMEM. The model evaluation was performed by the
      bootstrap approach and visual predictive check. RESULTS: A two-compartment model
      with a lag time best described the data. The estimated mean apparent clearance
      (CL/F) was 14.5 l/h with an interindividual variability of 45.2%. The estimated
      mean CL/F was found to be lower than the values previously reported. The
      estimated mean apparent volume of the central compartment was 12.2 l with an
      interindividual variability of 166%. None of the covariates were found to
      significantly influence MPA pharmacokinetics. CONCLUSION: In this study, a
      population pharmacokinetic model of MPA in severe lupus nephritis patients was
      successfully developed. The mean pharmacokinetic parameters were estimated and a
      high interindividual variability of MPA in this population was observed. This
      provides evidence to show that individualizing dosage regimens in this population
      is crucial. The model developed in this study could be used to obtain initial
      information for MPA dose adjustments in Thai and Asian patients with lupus
      nephritis. Further studies are required to validate the results and clarify the
      influence of covariates on MMF pharmacokinetics.

PMID- 22456299
TI  - Cost comparison of outpatient treatment with granulocyte colony-stimulating
      factors (G-CSF) in Germany.
AB  - BACKGROUND: Granulocyte colony-stimulating factors (G-CSF), are available for
      prevention of neutropenia and reduction of its complications in cytostatic
      chemotherapy. The purpose of this analysis was to determine the consumption rates
      for various G-CSF and to compare outpatient medication costs per patient and
      treatment cycle. METHODS: Prescription data of statutory health insurance members
      in Germany (IMS(r)LRx database) with G-CSF prescriptions between January 2008 and
      July 2010 were evaluated. A period of observation of at least 6 months prior to
      and after the G-CSF prescription was required. RESULTS: Prescription data of
      8,726 patients treated with original filgrastim, 4,240 with biosimilar
      filgrastim, 6,456 with lenograstim, and 9,939 with pegfilgrastim were analyzed.
      The regression model showed statistically significant costreducing effects per
      cycle for treatment with lenograstim compared with non-lenograstim (-0.47 vs.
      original filgrastim; -0.15 vs. biosimilar filgrastim; -1.04 vs. pegfilgrastim;
      each p < 0.0001). This result has been adjusted for patient age, gender, number
      of injections, and prescribing specialist group. CONCLUSIONS: Treatment with the
      original preparation lenograstim is significantly cheaper compared to the other
      two original drugs and biosimilar. The costs of G-CSF treatment with the original
      preparation lenograstim and the filgrastim biosimilars are in a similar range,
      but with a significantly lower cost for lenograstim. Compared to their reference
      product the biosimilars thus show a cost advantage.

PMID- 22456300
TI  - QT effect of semagacestat at therapeutic and supratherapeutic doses.
AB  - OBJECTIVE: This thorough QT/ QT interval corrected for heart rate (QTc) study was
      designed to assess the potential of semagacestat, a functional gamma-secretase
      inhibitor, to delay cardiac repolarization. METHODS: In this Phase I, single
      dose, randomized, 4-period crossover study, semagacestat was compared with
      placebo in 54 healthy male and female subjects between the ages of 19 and 63
      years, inclusive. Each study period included single oral-dose administrations of
      semagacestat 140 mg, semagacestat 280 mg, moxifloxacin 400 mg, or placebo. Study
      subjects and the investigator were blinded to the identity of semagacestat and
      placebo; however, moxifloxacin was administered as open-label. Moxifloxacin was
      compared with placebo for assay sensitivity analysis. Pharmacokinetic parameters
      were also assessed. RESULTS: For each QTc, the upper bound of the 2-sided 90%
      confidence interval (CI) for the least squares mean difference between
      semagacestat (at both the 140- and 280-mg dose levels) and placebo was < 10 msec
      at all time points, and thus, within the limits set for clinical relevance in
      regulatory guidelines. CONCLUSIONS: The results of this study indicate that
      single doses of 140 and 280 mg semagacestat did not prolong QTc to a clinically
      significant degree.

PMID- 22456301
TI  - Myoclonus precipitated by oral suspension of oxcarbazepine in idiopathic
      generalized epilepsy.
AB  - Oxcarbazepine (OXC) is widely registered for the treatment of partial seizures
      and generalized tonic-clonic seizures (GTCS). Myoclonic seizures induced by OXC
      are uncommon. We report a child with idiopathic generalized epilepsy who
      developed myoclonic seizures and had an abnormal electroencephalogram (EEG) when
      oral suspension of OXC was introduced. This study suggests that oral suspension
      of OXC can precipitate myoclonus.

PMID- 22456302
TI  - Severe hypoglycemia associated with levofloxacin in Type 2 diabetic patients
      receiving polytherapy: two case reports.
AB  - OBJECTIVE: Although hypoglycemia is known to be associated with levofloxacin,
      patients are continually being hospitalized because of this adverse event. Here
      we have reported two further cases of severe hypoglycemia and discussed the
      possibility that the hypoglycemia is the result of interactions between
      levofloxacin and certain drugs, in order to alert physicians to be aware that
      geriatric patients, particularly those with Type 2 diabetes and in polytherapy,
      are at risk of showing this adverse reaction. CASES SUMMARY: A 91-year-old woman
      with Type 2 diabetes on metformin and glibenclamide, also under treatment with
      oral antihypertensive drugs, platelet antiaggregant, low-molecular- weight
      heparin and buprenorphine, was prescribed levofloxacin for a bacterial infection.
      Liver function and renal function parameters were within normal limits. After
      repeated administration of levofloxacin, her serum glycemic levels had decreased
      to 47 mg/dl and the patient was in a coma. After stopping levofloxacin her
      glycemia level returned to the normal value. A 61 year-old male, affected by
      tonsillar squamous cell carcinoma, with Type 2 diabetes on metformin and
      glibenclamide, under treatment with low-molecular-weight heparin for deep venous
      thrombosis, hydromorphone and undergoing nutritional support, was treated with
      levofloxacin for a bacterial infection. After 72 h the patient was unresponsive
      and his blood glucose levels were 38 mg/dl. After discontinuation of levofloxacin
      administration the patient was treated with glucose infusion and his glycemic
      values gradually returned to the normal range. DISCUSSION: The causality
      relationship between the levofloxacin and the hypoglycemia was established using
      Naranjo's ADR probability scale. These case reports confirm the literature data
      that serious hypoglycemia may develop due to the use of levofloxacin and appears
      to occur most frequently in elderly patients with Type 2 diabetes who are
      receiving oral hypoglycemic agents. We described the possible pharmacokinetic and
      pharmacodinamic mechanisms of the interaction between levofloxacin and the other
      drugs. CONCLUSIONS: We hypothesized that the concomitant use of several drugs and
      particularly levofloxacin in association with oral antidiabetic drugs, opioid
      analgesics and low-molecular-weight heparin could concur to cause this side
      effect. The safety and tolerability of this anti-infective agent should be
      revised urgently.

PMID- 22456303
TI  - Effect of food on the bioavailability of lesogaberan given as an oral solution or
      as modified-release capsules in healthy male volunteers.
AB  - The novel Type B gamma-aminobutyric acid (GABAB)-receptor agonist lesogaberan
      (AZD3355) has been evaluated as an add-on to proton pump inhibitor treatment for
      gastroesophageal reflux disease, but the effect of food on the bioavailability of
      this compound has not been assessed. In this openlabel crossover study, healthy
      males received single 100 mg doses of lesogaberan (oral solution (A) or oral
      modified release (MR) capsules with a dissolution rate of 50% (B) or 100% (C)
      over 4 h) with and without food. Blood plasma concentrations of lesogaberan were
      assessed over 48 h. A log-transformed geometric mean Cmax and AUC ratio within
      the 90% confidence interval (CI) range (0.80 - 1.25) was defined as excluding a
      clinically relevant food effect. Overall, 57 subjects completed the study. Only
      the oral lesogaberan solution had a fed/fasting Cmax ratio outside the 90% CI
      range (Cmax ratio: 0.76). AUC ratios were within the 90% CI limits for all three
      lesogaberan formulations. The only substantial change in tmax associated with
      food intake was observed for the oral solution (1.0 h without food, 1.8 h with
      food). In conclusion, a clinically relevant food effect could be excluded for the
      lesogaberan MR formulations, but not for the oral lesogaberan solution.

PMID- 22456304
TI  - Laparoendoscopic single-site surgery in patients with benign adnexal disease: a
      comparative study.
AB  - BACKGROUND: Laparoendoscopic single-site surgery (LESS) is becoming increasingly
      popular in different disciplines. Evidence is scarce about its utility in
      gynecologic surgery. AIM: To compare our initial experience using LESS for benign
      adnexal disease to traditional laparoscopy. METHODS: Since November 2008, we have
      performed LESS in 28 patients diagnosed with benign adnexal disease (group I).
      Patients with adnexal masses and a body mass index <35 were selected. An age
      matched control group of patients with similar diagnoses who underwent
      traditional operative laparoscopy was included (n = 50; group II). RESULTS: Both
      groups were comparable with regard to age, body mass index, preoperative
      diagnosis, indication of surgery and history of previous abdominal surgery. The
      operative blood loss ranged from minimal to <50 ml for both groups. The mean +/-
      SD duration of surgery in group I (45 +/- 19.5 min) was comparable to that of
      group II (46.4 +/- 18.3 min). The duration of hospital stay was <24 h in both
      groups. Minimal use of postoperative narcotics was required in study subjects and
      no intraoperative complications occurred. CONCLUSIONS: LESS for benign adnexal
      disease is feasible in patients with or without previous surgery and is
      comparable to traditional laparoscopic surgery. Additional investigation is
      needed to evaluate the safety, cost-effectiveness and long-term outcomes of this
      new approach.

PMID- 22456305
TI  - The additional value of bioelectrical impedance analysis-derived muscle mass as a
      screening tool in geriatric assessment for fall prevention.
AB  - BACKGROUND: The decline in skeletal muscle in old age is a factor in the
      development of functional limitations. OBJECTIVE: The objective of this study was
      to assess if there is a correlation between muscle mass based on bioelectrical
      impedance analysis (BIA) detection and the fall incidence in nursing home
      residents and to examine the risk factors for falling in nursing home residents.
      METHODS: This prospective cohort study was part of a longitudinal study on
      nutritional issues in 52 nursing homes in Antwerp (Belgium) from October 2007 to
      April 2008. Two hundred and seventy-six people aged 65 years and older were
      included. Each subject was assessed with BIA, the timed get-up-and-go test, the
      Katz score, the Mini Nutritional Assessment - Short Form and the 36-Item Short
      Form Health Survey. The primary outcome parameter was fall incidence during the
      study. RESULTS: The prevalence of sarcopenia varied from 24.3 to 81.5% depending
      on which definition was used. No association was found between BIA-derived muscle
      mass and fall incidence. Logistic regression analysis showed that gait speed
      (odds ratio 1.029; p = 0.003) and mental health (odds ratio 0.981; p = 0.015) are
      significantly associated with fall incidence in nursing homes. A receiver
      operating characteristic curve showed that none of the BIA-derived muscle
      parameters are good predictors of the risk of falling. CONCLUSIONS: This study
      shows that there is no association between sarcopenia based on BIA and fall
      incidence and that BIA-derived muscle mass has no additional value in predicting
      fall incidents compared to the timed get-up-and-go test.

PMID- 22456306
TI  - Patterning-induced strain relief in single lithographic SiGe nanostructures
      studied by nanobeam x-ray diffraction.
AB  - The continued downscaling in SiGe heterostructures is approaching the point at
      which lateral confinement leads to a uniaxial strain state, giving high
      enhancements of the charge carrier mobility. Investigation of the strain
      relaxation as induced by the patterning of a continuous SiGe layer is thus of
      scientific and technological importance. In the present work, the strain in
      single lithographically defined low-dimensional SiGe structures has been directly
      mapped via nanobeam x-ray diffraction. We found that the nanopatterning is able
      to induce an anisotropic strain relaxation, leading to a conversion of the strain
      state from biaxial to uniaxial. Its origin is fully compatible with a pure
      elastic deformation of the crystal lattice without involving plastic relaxation
      by injection of misfit dislocations.

PMID- 22456307
TI  - Isoflavones inhibit the clonogenicity of human colon cancer cells.
AB  - Isoflavones are a class of polyphenols that contain various substituents such as
      hydroxy, methoxy, and glycosyl groups. Methoxy groups are known to increase cell
      permeability and stability, but small structural changes can result in large
      differences in biological activity. In this study, the anticancer activities of
      several methoxy isoflavones were tested using a clonogenic survival assay. The
      relationship between structural properties of methoxy isoflavones and their
      anticancer activities on HCT116 colon cancer cell lines were studied
      quantitatively using comparative molecular field analysis and comparative
      molecular similarity indices analysis. The purpose of this study was to identify
      structural changes in isoflavones that increase the inhibitory effect on HCT116
      colon cancer cell clonogenicity.

PMID- 22456308
TI  - The exon 3-deleted/full-length growth hormone receptor polymorphism and response
      to growth hormone therapy in growth hormone deficiency and Turner syndrome: a
      multicenter study.
AB  - BACKGROUND/AIM: The exon 3-deleted/full-length (d3/fl) growth hormone (GH)
      receptor (GHR) polymorphism has been associated with responsiveness to GH therapy
      in some diagnostic groups. However, there are still controversies on this issue.
      To evaluate the effect of the GHR exon 3 polymorphism on growth after 1 and 2
      years of GH therapy in Turkish patients with GH deficiency (GHD) and Turner's
      syndrome (TS) and the distribution of GHR exon 3 isoforms. MATERIALS AND METHODS:
      218 patients with GHD (125 males/93 females) and 43 patients with TS were
      included in the study. The control group included 477 healthy adults aged from 18
      to 57 years (54 females/423 males). Anthropometric parameters and insulin-like
      growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were evaluated annually.
      GHR isoforms were studied using simple multiplex PCR. Height and body mass index
      were expressed as standard deviation score (SDS). RESULTS: There were no
      differences among TS, GHD and healthy adults regarding the distribution of GHR
      exon 3 isoforms (fl/fl, fl/d3 and d3/d3). There was a significant increase in
      height SDS in both diagnostic groups on GH therapy; however, there were neither
      differences in height SDS and Deltaheight velocity between fl/fl, fl/d3 and d3/d3
      groups nor a correlation between the distribution of GHR exon 3 isoforms and
      change in IGF-1 SDS and IGFBP-3 SDS levels on GH therapy in either of the
      diagnostic groups. There was also no gender difference in GHR isoforms in healthy
      adults. CONCLUSION: The results suggest that responsiveness to GH therapy does
      not depend on the exon 3 GHR genotypes in GHD and TS patients.

PMID- 22456309
TI  - Effects of dietary vitamin B1 (thiamine) and magnesium on the survival, growth
      and histological indicators in lake trout (Salvelinus namaycush) juveniles.
AB  - An interaction of two essential nutrients, thiamine and magnesium (Mg) has been
      documented in in vitro and in vivo studies in mammalian metabolism. However, the
      role of this association in poikilothermic vertebrates, such as fish, remains
      elusive. The purpose of this study was first to investigate the effects of
      dietary thiamine and Mg, and their interaction in lake trout and second to better
      understand the mechanism leading to early mortality syndrome (EMS), which is
      caused by a low thiamine level in embryos of many species of salmonids in the
      wild. Semi-purified diets (SPD) were prepared to accomplish 2 * 2 factorial
      design that were either devoid of or supplemented with thiamine mononitrate (20
      mg/kg diet), magnesium oxide (700 mg/kg diet), or both. Lake trout alevins at the
      swim-up stage were fed for 10 wk one of the SPD diets or a commercial diet at the
      same rate (2.0-1.5%) based on recorded biomass. Our results showed that the
      concentrations of thiamine in the trunk muscle and Mg of whole body were closely
      associated with the dietary level of two nutrients. The interaction of low
      dietary Mg and thiamine resulted in apparently worsened overt symptoms of
      thiamine deficiency in lake trout leading to a higher mortality of fish during
      the seven week long trial (P<0.05). The fish fed a thiamine-devoid and Mg
      supplemented diet were presumed to survive longer (10 wk) than the fish fed diets
      devoid of both nutrients (discontinued after 7th wk due to high mortality).
      However, we did not observe histopathological changes in the brain and liver
      corresponding to thiamine concentrations in tissues. These data suggest that Mg
      enhanced utilization of the thiamine remaining in the fish body and its
      interdependence was consistent with observations in mammals. EMS severity might
      be worsened when Mg is deficient in parental diets (and consequently in yolk sac)
      and/or first feed.

PMID- 22456310
TI  - Daytime restricted feeding modifies 24 h rhythmicity and subcellular distribution
      of liver glucocorticoid receptor and the urea cycle in rat liver.
AB  - The timing system in mammals is formed by a set of peripheral biological clocks
      coordinated by a light-entrainable pacemaker located in the suprachiasmatic
      nucleus. Daytime restricted feeding (DRF) modifies the circadian control and
      uncouples the light-dependent physiological rhythmicity, food access becoming the
      principal external time cue. In these conditions, an alternative biological clock
      is expressed, the food-entrainable oscillator (FEO). Glucocorticoid hormones are
      an important part of the humoral mechanisms in the daily synchronisation of the
      metabolic response of peripheral oscillators by the timing system. A peak of
      circulating corticosterone has been reported before food access in DRF protocols.
      In the present study we explored in the liver the 24 h variations of: (1) the
      subcellular distribution of glucocorticoid receptor (GCR), (2) the activities of
      the corticosterone-forming and NADPH-generating enzymes (11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD-1) and hexose-6-phosphate dehydrogenase
      (H6PDH)), and, (3) parameters related with the urea cycle (circulating urea and
      activities of carbamoyl phosphate synthetase and ornithine transcarbamylase)
      elicited by DRF. The results showed that DRF promoted an increase of more than
      two times of the hepatic GCR, but exclusively in the cytosolic compartment, since
      the GCR in the nuclear fraction showed a reduction. No changes were observed in
      the activities of 11beta-HSD-1 and H6PDH, but the rhythmicity of all of the urea
      cycle-related parameters was modified. It is concluded that liver glucocorticoid
      signalling and the urea cycle are responsive to feeding-restricted schedules and
      could be part of the FEO.

PMID- 22456311
TI  - Soluble platelet/endothelial cell adhesion molecule (sPECAM)-1 is increased in
      polycystic ovary syndrome and related to endothelial dysfunction.
AB  - Striking evidence indicates endothelial impairment in polycystic ovary syndrome
      (PCOS) but the mechanisms linking PCOS status to cardiovascular risk remain
      elusive. Platelet/endothelial cell adhesion molecule (PECAM)-1 is a soluble (s)
      signaling molecule involved in inflammation and angiogenesis with predictive
      value for endothelial dysfunction in patients at risk. In a prospective,
      controlled study, sPECAM-1 levels and the relationships to metabolic,
      inflammatory and vascular PCOS traits were evaluated in 26 patients and 29-age-
      and body mass index-matched controls. To assess endothelial injury, carotid
      artery intimae-media thickness (CIMT) and brachial artery flow-mediated
      vasodilatation (FMD) were employed. Of the 26 women with PCOS, 25 completed a six
      month metformin combined with ethinylestradiol 0.3 mg/drospirenone 3 mg therapy.
      Soluble PECAM-1 levels were increased in PCOS (p = 0.018 vs. Controls) and
      significantly decreased at follow-up (p = 0.0002). Smoking and weight had no
      effect on sPECAM-1 dynamics. In both univariate and multivariate analysis, basal
      sPECAM-1 was inversely related to FMD (r = -0.311, p = 0.021) but not CIMT. To
      conclude, sPECAM-1 is increased in PCOS, an effect reversed by combined metformin
      and anti-androgenic contraceptive therapy. Elevated sPECAM-1 contributes to
      endothelial dysfunction however further studies are inquired to assess its
      relevance as biomarker and potential therapeutic target in PCOS.

PMID- 22456313
TI  - Structural and functional aspects of winged-helix domains at the core of
      transcription initiation complexes.
AB  - The winged helix (WH) domain is found in core components of transcription systems
      in eukaryotes and prokaryotes. It represents a sub-class of the helix-turn-helix
      motif. The WH domain participates in establishing protein-DNA and protein-protein
      interactions. Here, we discuss possible explanations for the enrichment of this
      motif in transcription systems.

PMID- 22456314
TI  - Prp19C and TREX: interacting to promote transcription elongation?and mRNA export.
AB  - During transcription of protein coding genes by RNA Polymerase II the mRNA is
      processed and packaged into an mRNP. Among the proteins binding
      cotranscriptionally to the mRNP are mRNA export factors. One of the protein
      complexes thus coupling transcription to mRNA export is the TREX complex.
      However, despite the fact that TREX was identified and characterized about a
      decade ago, it had remained enigmatic how TREX is recruited to genes. The
      conserved Prp19 complex (Prp19C) has long been known for its function in
      splicing. We recently identified Prp19C to be essential for a second step in gene
      expression namely TREX occupancy at transcribed genes, answering this long
      standing question but also raising new ones.

PMID- 22456315
TI  - New insights into the SAGA complex from studies of the Tra1 subunit in budding
      and fission yeast.
AB  - The SAGA complex is a conserved, multifunctional co-activator that controls the
      transcription of many inducible genes in response to environmental changes.
      Recent studies have provided new insights into the functions of one of its
      subunits, Tra1/TRRAP, and suggest that it controls SAGA activity in response to
      external stimuli.

PMID- 22456316
TI  - Cross-species ChIP-seq studies provide insights into regulatory strategies of
      PPARgamma in adipocytes.
AB  - Three recent studies have investigated interspecies retention of binding sites of
      peroxisome proliferator-activated receptor gamma (PPARgamma), the master
      regulator of adipocyte differention, between mouse and human adipocytes. Here we
      discuss the major findings and demonstrate that retention of binding events is
      highly context-dependent.

PMID- 22456318
TI  - RNA polymerase II transcription on the fast lane.
AB  - Transcription by RNA polymerase II is the process that copies DNA into RNA
      leading to the expression of a specific gene. Averaged estimates of polymerase
      elongation rates in mammalian cells have been shown to vary between 1 and 4
      kilobases per minute. However, recent advances in live cell imaging allowed
      direct measurements of RNA biogenesis from a single gene exceeded 50 kb.min(-1) .
      This unexpected finding opens novel and intriguing perspectives on the control of
      metazoan transcription.

PMID- 22456317
TI  - MINIYO and transcriptional elongation: lifting the roadblock to differentiation.
AB  - Inhibiting transcriptional elongation is a recurrent mechanism to keep cells in
      an undifferentiated, pluripotent state in metazoans. It remains, however, unclear
      whether lifting the barrier to transcriptional elongation acts as the switch to
      initiate differentiation in those organisms. Recent results suggest that such a
      mechanism for turning on differentiation does exist in plants. We argue that
      targeting the elongation phase of transcription may be a solution adopted widely
      in evolution to allow for the global transcriptional changes needed in cellular
      differentiation.

PMID- 22456319
TI  - Gene expression at the Iguazu Falls: a report from the "Gene Expression and RNA
      Processing" symposium; Iguazu Falls, Province of Misiones, Argentina.
AB  - The fourth edition of the "Gene Expression and RNA Processing" symposium took
      place this year at the Iguazu Falls, one of the most renowned South American
      natural wonders, and brought together an outstanding array of speakers from all
      over the world to discuss mechanisms of transcriptional regulation and RNA
      processing.

PMID- 22456320
TI  - The relative importance of transcription rate, cryptic transcription and mRNA
      stability on shaping stress responses in yeast.
AB  - It has been recently stated that stress-responding genes in yeast are enriched in
      cryptic transcripts and that this is the cause of the differences observed
      between mRNA amount and RNA polymerase occupancy profiles. Other studies have
      shown that such differences are mainly due to modulation of mRNA stabilities.
      Here we analyze the relationship between the presence of cryptic transcripts in
      genes and their stress response profiles. Despite some of the stress-responding
      gene groups being indeed enriched in specific classes of cryptic transcripts, we
      found no statistically significant evidence that cryptic transcription is
      responsible for the differences observed between mRNA and transcription rate
      profiles.

PMID- 22456321
TI  - A label-free fluorescence DNA probe based on ligation reaction with quadruplex
      formation for highly sensitive and selective detection of nicotinamide adenine
      dinucleotide.
AB  - A simple label-free fluorescent sensing scheme for sensitive and selective
      detection of nicotinamide adenine dinucleotide (NAD(+)) has been developed based
      on DNA ligation reaction with ligand-responsive quadruplex formation. This
      approach can detect 0.5 nM NAD(+) with high selectivity against other NAD(+)
      analogs.

PMID- 22456322
TI  - Monte-Carlo dosimetry on a realistic cell monolayer geometry exposed to alpha
      particles.
AB  - The energy and specific energy absorbed in the main cell compartments (nucleus
      and cytoplasm) in typical radiobiology experiments are usually estimated by
      calculations as they are not accessible for a direct measurement. In most of the
      work, the cell geometry is modelled using the combination of simple mathematical
      volumes. We propose a method based on high resolution confocal imaging and ion
      beam analysis (IBA) in order to import realistic cell nuclei geometries in Monte
      Carlo simulations and thus take into account the variety of different geometries
      encountered in a typical cell population. Seventy-six cell nuclei have been
      imaged using confocal microscopy and their chemical composition has been measured
      using IBA. A cellular phantom was created from these data using the ImageJ image
      analysis software and imported in the Geant4 Monte-Carlo simulation toolkit.
      Total energy and specific energy distributions in the 76 cell nuclei have been
      calculated for two types of irradiation protocols: a 3 MeV alpha particle
      microbeam used for targeted irradiation and a 239Pu alpha source used for large
      angle random irradiation. Qualitative images of the energy deposited along the
      particle tracks have been produced and show good agreement with images of DNA
      double strand break signalling proteins obtained experimentally. The methodology
      presented in this paper provides microdosimetric quantities calculated from
      realistic cellular volumes. It is based on open-source oriented software that is
      publicly available.

PMID- 22456323
TI  - Imaging neuroinflammation after stroke: current status of cellular and molecular
      MRI strategies.
AB  - Cellular and molecular magnetic resonance imaging (MRI) strategies for studying
      the spatiotemporal profile of neuroinflammatory processes after stroke are
      increasingly being explored since the first reports appeared about a decade ago.
      These strategies most often employ (super)paramagnetic contrast agents, such as
      (ultra)small particles of iron oxide and gadolinium chelates, for MRI-based
      detection of specific leukocyte populations or molecular inflammatory markers
      that are involved in the pathophysiology of stroke or plasticity. In this review
      we describe achievements, limitations and prospects in the field of cellular and
      molecular MRI of neuroinflammation in preclinical and clinical stroke. Several
      studies in rodent stroke models have demonstrated the application of MRI contrast
      agents for imaging of monocyte infiltration, which served as the foundation for
      pilot (small-scale proof-of-concept) cellular MRI studies in stroke patients.
      This may be achieved with isolated cells that are loaded with contrast agent
      through in vitro incubation prior to systemic administration. Alternatively,
      superparamagnetic iron oxide particles may be directly injected into the
      circulation to allow in vivo uptake by phagocytic cells. Both strategies have
      been successfully employed to measure the spatiotemporal profile of invasion of
      monocytes in and around cerebral ischemic lesions in experimental stroke models.
      Molecular MRI studies with target-specific contrast agents have shown the
      capability for in vivo detection of molecular markers after experimental stroke.
      For example, (super)paramagnetic micro- or nanoparticles that are functionalized
      with a ligand (e.g. an antibody) for specific cell adhesion molecules, such as E
      selectin and vascular cell adhesion molecule 1 (VCAM-1), can target inflamed,
      activated endothelium, whose presence can subsequently be detected with MRI.
      Present applications remain limited as most of the currently available contrast
      agents provide relatively poor contrast enhancement, which is not easily
      discriminated from endogenous sources of tissue contrast. Nevertheless, current
      developments of more efficient particles, such as biocompatible liposomes,
      micelles and nanoemulsions that can contain high payloads of (super)paramagnetic
      material as well as other substances, such as dyes and drugs, may open a window
      of opportunities for promising translational multimodal imaging strategies that
      enable in vivo assessment of (neuroinflammatory) disease markers, therapeutic
      targets as well as drug delivery after stroke.

PMID- 22456324
TI  - Coincidence signaling of dopamine D1-like and M1 muscarinic receptors in the
      regulation of cyclic AMP formation and CREB phosphorylation in mouse prefrontal
      cortex.
AB  - In the prefrontal cortex, dopamine D1-like and M1 muscarinic receptors are both
      involved in the regulation of attentional, cognitive and emotional processes but
      so far no information has been provided on their functional interaction. In the
      present study we show that in mouse medial prefrontal cortex, concomitant
      activation of M1 muscarinic receptors potentiated D1-like receptor-induced cyclic
      AMP formation through a mechanism involving activation of Gq/11 and the release
      of G protein betagamma subunits. Immunohistochemical studies indicated that the
      adenylyl cyclase isoforms AC2 and AC4 are expressed in mouse prefrontal cortex
      and that they colocalize with D1-like receptors with a greater association for
      AC4. In primary cultures of frontal cortex neurons, D1-like receptor-induced
      Ser133 phosphorylation of the transcription factor cyclic AMP-responsive element
      binding protein (CREB) was potentiated by concurrent stimulation of M1 receptors.
      Suppression of AC4 expression with small interfering RNA transfection reduced D1
      stimulation of cyclic AMP formation and CREB phosphorylation and abolished the M1
      potentiation, whereas knockdown of AC2 had no significant effects. These data
      indicate that in mouse prefrontal cortex Gq/11-coupled M1 receptor and Gs-coupled
      D1-like receptor inputs converge on AC4 with a consequent enhancement of cyclic
      AMP formation and signaling to the nucleus.

PMID- 22456325
TI  - A calcium-sensitive promoter construct for gene therapy.
AB  - Targeting diseased cells is a challenging issue in both pharmacological and
      biological therapeutics. Gene therapy is emerging as a novel approach for
      treating rare diseases and for illnesses for which there is no other alternative.
      An important limitation of gene therapy has been the off-target effects and
      therefore efforts have been focused on increasing the specificity of gene
      transfer to the targeted organ. Here, we describe a promoter containing six
      nuclear factor of activated T cells (NFAT) consensus sequences, which is as
      efficient as the cytomegalovirus (CMV) promoter to drive expression in vascular
      smooth muscle cells both in vitro and in vivo. In contrast to the CMV promoter it
      is activated in a Ca(2+)-dependent manner after endoplasmic reticulum depletion
      and allows the transgene expression only in proliferative/diseased cells.
      Overexpression of sarco/endoplasmic reticulum (SR/ER) Ca(2+) ATPase 2a under the
      control of this NFAT promoter inhibits restenosis after angioplasty in rats. In
      conclusion, this promoter may be useful for gene therapy in vascular
      proliferative diseases and other diseases involving upregulation of the NFAT
      pathway.

PMID- 22456326
TI  - Vein graft failure: current clinical practice and potential for gene
      therapeutics.
AB  - Autologous saphenous vein is commonly used as a conduit to bypass atherosclerotic
      lesions in coronary and femoral arteries. Despite the wide use of arterial
      conduits, which are less susceptible to complications and failure, as alternative
      conduits, the saphenous vein will continue to be used in coronary artery bypass
      grafting until acceptable alternative approaches are evaluated. Hence,
      preservation of vein graft patency is essential for the long-term success. Gene
      therapy is attractive in this setting as an ex-vivo technology to genetically
      manipulate the conduit before grafting. The use of safe and efficient vectors for
      delivery is a necessity as well as a strategy to improve patency in the long
      term. Here, we review the current clinical practice, the pathogenesis of bypass
      graft failure and adenovirus-mediated gene therapy strategies designed to improve
      late vein graft failure by modulation of smooth muscle cells in the vein wall.

PMID- 22456327
TI  - Cathelicidin gene therapy: a new therapeutic option in ulcerative colitis and
      beyond?

PMID- 22456328
TI  - Electroporation-mediated gene transfer directly to the swine heart.
AB  - In vivo gene transfer to the ischemic heart via electroporation holds promise as
      a potential therapeutic approach for the treatment of heart disease. In the
      current study, we investigated the use of in vivo electroporation for gene
      transfer using three different penetrating electrodes and one non-penetrating
      electrode. The hearts of adult male swine were exposed through a sternotomy.
      Eight electric pulses synchronized to the rising phase of the R wave of the
      electrocardiogram were administered at varying pulse widths and field strengths
      following an injection of either a plasmid encoding luciferase or one encoding
      green fluorescent protein. Four sites on the anterior wall of the left ventricle
      were treated. Animals were killed 48 h after injection and electroporation and
      gene expression was determined. Results were compared with sites in the heart
      that received plasmid injection but no electric pulses or were not treated. Gene
      expression was higher in all electroporated sites when compared with injection
      only sites demonstrating the robustness of this approach. Our results provide
      evidence that in vivo electroporation can be a safe and effective non-viral
      method for delivering genes to the heart, in vivo.

PMID- 22456329
TI  - Endostatin inhibits angiogenesis in hepatocellular carcinoma after transarterial
      chemoembolization.
AB  - BACKGROUND/AIMS: This study aims to investigate the influence of endostatin on
      angiogenesis in hepatocellular carcinoma (HCC) after transarterial
      chemoembolization (TACE). METHODOLOGY: Ninety-five patients with HCC were
      enrolled. Twenty-six patients received initial liver resection without
      preoperative TACE (non-TACE), 24 received preoperative TACE without endostatin
      (TACE), 22 received endostatin (15mg/m2) right after TACE intravenously (TACE-V)
      and 23 received endostatin (15mg/m2) through the hepatic artery during TACE (TACE
      A). TACE was performed using Gemcitabine 1000mg/m2 (emulsified with lipiodol, 10
      12mL), cisplatin 40 mg/m2 and 5-fluorouracil 500mg/m2 through the hepatic artery
      feeding the tumor. Patients received liver resection 4 weeks after second course
      of TACE. RESULTS: The mean microvessel density (MVD) was 32.23+/-12.71, 57.46+/
      18.38, 44.36+/-15.13 and 43.48+/-15.59 in non-TACE, TACE, TACE-V and TACE-A group
      respectively. The positive rate of vascular endothelial growth factor (VEGF)
      expression was 46.15%, 91.67%, 77.27% and 73.91% in non-TACE, TACE, TACE-V and
      TACE-A groups, respectively. Compared to the non-TACE group, MVD and VEGF
      expression in TACE, TACE-V and TACE-A groups were significantly higher (p<0.05).
      MVD and VEGF expression in the TACE-V and TACE-A groups were significantly lower
      than in the TACE group (p<0.05). CONCLUSIONS: Endostatin could significantly
      repress angiogenesis in HCC after TACE by down-regulating expression of VEGF.

PMID- 22456330
TI  - Fetal and maternal complications after selective fetoscopic laser surgery for
      twin-to-twin transfusion syndrome: a single-center experience.
AB  - OBJECTIVE: To report the incidence of fetal and maternal complications after
      selective fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS).
      METHODS: A total of 150 cases of TTTS were treated from January 2004 to June 2009
      (period 1, 2004-2006, 62 cases; period 2, 2007 to June 2009, 88 cases). Fetal
      complications (double and single intrauterine fetal death, recurrence of TTTS,
      twin anemia-polycythemia sequence (TAPS), reversal of TTTS, cerebral lesions in
      one twin) and maternal complications were recorded, and retrospectively analyzed.
      RESULTS: Nineteen (12.6%), 58 (38.7%), 61 (40.7%) and 12 cases (8.0%) were
      classified preoperatively as Quintero stage I, II, III and IV, respectively. The
      anterior placenta was described in 73 cases (48.6%). Double and single fetal
      death occurred overall in 7.3 and 36.0% of cases, respectively. The rate of
      recurrence was 11.3%, of TAPS 3.3%, and of reversal of TTTS 1.3%. Cerebral
      lesions were diagnosed in 3 donors (2.0%). Eighteen cases (12.0%) of fetal
      complications had a second procedure (6 repeat laser, 4 serial amnioreduction, 8
      bipolar cord coagulation). Pregnancies undergoing a second procedure delivered at
      a median gestational age of 30.2 weeks compared to 32.1 weeks for those not
      repeating (p = 0.04). Perinatal survival of at least one twin improved from 66.1
      to 79.5% (p = 0.06) in the two consecutive periods. For every 10 laser surgeries
      performed, there was an average improvement of 1.5% in the predicted percentage
      of survival of at least one twin (OR 1.09, 95% CI 1.00-1.19). Major maternal
      complications occurred in 9 cases (6.0%), 3 of which required admission to
      intensive care unit. CONCLUSIONS: Fetal complications are common after fetoscopic
      laser surgery. In this experience, an increasing number of procedures improved
      the performance of a new fetoscopic laser center.

PMID- 22456331
TI  - The directional flow of visual information transfer between pedestrians.
AB  - Close behavioural coupling of visual orientation may provide a range of adaptive
      benefits to social species. In order to investigate the natural properties of
      gaze-following between pedestrians, we displayed an attractive stimulus in a
      frequently trafficked corridor within which a hidden camera was placed to detect
      directed gaze from passers-by. The presence of visual cues towards the stimulus
      by nearby pedestrians increased the probability of passers-by looking as well. In
      contrast to cueing paradigms used for laboratory research, however, we found that
      individuals were more responsive to changes in the visual orientation of those
      walking in the same direction in front of them (i.e. viewing head direction from
      behind). In fact, visual attention towards the stimulus diminished when oncoming
      pedestrians had previously looked. Information was therefore transferred more
      effectively behind, rather than in front of, gaze cues. Further analyses show
      that neither crowding nor group interactions were driving these effects,
      suggesting that, within natural settings gaze-following is strongly mediated by
      social interaction and facilitates acquisition of environmentally relevant
      information.

PMID- 22456332
TI  - Oncology trials--the elephant in the room.

PMID- 22456333
TI  - Lebanese parents' experiences with a child with cancer.
AB  - BACKGROUND: The impact of childhood cancer on the family has been studied in
      different cultures and continues to be an object of study and concern, In
      Lebanon, a country of 4 million people 282 new pediatric cases of cancer age <20
      years diagnosed in 2004 were reported in 2008. OBJECTIVES: The purpose of this
      study was to explore the experiences of Lebanese families living with a child
      with cancer. METHOD: The study followed purposeful sampling in which 12 parents
      (mother or father) of a child with cancer were interviewed. Data were analyzed
      following the hermeneutical process as described by Diekelmann and Ironsides
      (1998). RESULTS: A constitutive pattern "It is a continuous battle" and five
      themes emerged from the data analysis. Living with the shock of the diagnosis;
      Alterations in the quality of the family's life; Living with added burdens;
      Disease impact on the family and sibling dynamics; Living with uncertainty
      represent the major themes that emerged from the participants' experiences while
      living with a child with cancer. CONCLUSION: The study contributes to the
      knowledge that would help health care professionals understand the experiences
      and challenges that are faced by Lebanese families living with a child with
      cancer. This awareness would serve as a basis for health care professionals in
      general and nurses in particular to understand parents' experiences, and offer
      support, elicit communication of feelings, and examine possibilities for forming
      a partnership during the challenging course of the child's illness. Supported
      parents are more likely to provide more effective care to their child with
      cancer.

PMID- 22456334
TI  - Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage.
AB  - The cellular DNA damage response (DDR) machinery that maintains genomic integrity
      and prevents severe pathologies, including cancer, is orchestrated by signaling
      through protein modifications. Protein ubiquitylation regulates repair of DNA
      double-strand breaks (DSBs), toxic lesions caused by various metabolic as well as
      environmental insults such as ionizing radiation (IR). Whereas several components
      of the DSB-evoked ubiquitylation cascade have been identified, including RNF168
      and BRCA1 ubiquitin ligases, whose genetic defects predispose to a syndrome
      mimicking ataxia-telangiectasia and cancer, respectively, the identity of the
      apical E1 enzyme involved in DDR has not been established. Here, we identify
      ubiquitin-activating enzyme UBA1 as the E1 enzyme required for responses to IR
      and replication stress in human cells. We show that siRNA-mediated knockdown of
      UBA1, but not of another UBA family member UBA6, impaired formation of both
      ubiquitin conjugates at the sites of DNA damage and IR-induced foci (IRIF) by the
      downstream components of the DSB response pathway, 53BP1 and BRCA1. Furthermore,
      chemical inhibition of UBA1 prevented IRIF formation and severely impaired DSB
      repair and formation of 53BP1 bodies in G 1, a marker of response to replication
      stress. In contrast, the upstream steps of DSB response, such as phosphorylation
      of histone H2AX and recruitment of MDC1, remained unaffected by UBA1 depletion.
      Overall, our data establish UBA1 as the apical enzyme critical for ubiquitylation
      dependent signaling of both DSBs and replication stress in human cells, with
      implications for maintenance of genomic integrity, disease pathogenesis and
      cancer treatment.

PMID- 22456336
TI  - Chemical genetic induction of meiosis in Schizosaccharomyces pombe.
AB  - In the fission yeast Schizosaccharomyces pombe, meiosis is inhibited by the
      protein kinase Pat1, which phosphorylates and inactivates Mei2, an RNA binding
      protein essential for the initiation of meiosis. When diploid cells are deprived
      of nutrients, they initiate a cascade of events leading to the inactivation of
      Pat1 and entry into meiosis. Strains carrying the temperature-sensitive pat1-114
      allele are forced to enter into meiosis when shifted to the non-permissive
      temperature, independently of the ploidity of the cell. This system has been
      extensively used, since it is possible to achieve a highly synchronous meiosis,
      which is a must for any molecular or microscopic approach that aims to decipher
      the mechanisms governing meiosis. Here, we have designed a new system to obtain a
      similarly synchronous meiosis, but independently of temperature shifts. Thus, by
      introducing a mutation in the ATP pocket of Pat1, we have generated a protein
      kinase that, in the presence of small specific inhibitors, can be inactivated.
      This results in forced entry into meiosis without the need of a temperature
      shift, minimizing the introduction of heat shock or any other stress responses
      along the meiotic waves of transcription.

PMID- 22456335
TI  - MYC directs transcription of MCL1 and eIF4E genes to control sensitivity of
      gastric cancer cells toward HDAC inhibitors.
AB  - Histone deacetylases (HDACs) control fundamental physiological processes such as
      proliferation and differentiation. HDAC inhibitors (HDACi) induce cell cycle
      arrest and apoptosis of tumor cells. Therefore, they represent promising cancer
      therapeutics that appear particularly useful in combination therapies. Although
      HDACi are tested in current clinical trials, the molecular mechanisms modulating
      the cellular responses toward HDACi are incompletely understood. To gain insight
      into pathways that limit HDACi efficacy in gastric cancer, we treated a panel of
      gastric cancer cells with the clinically relevant HDACi suberoylanilide
      hydroxamic acid (SAHA). We report that higher expression levels of the anti
      apoptotic BCL2 family members MCL1 and BCL(XL) were detectable in cells with high
      inhibitory concentration 50 (IC(50)) values for SAHA. Using RNAi, we show that
      MCL1 and BCL(XL) lower the efficacy of SAHA. To find strategies to interfere with
      MCL1 and BCL(XL) expression, we investigated molecular regulation of both
      proteins. We show that specific siRNAs against c-MYC as well as pharmacological
      inhibition of this cancer-relevant transcription factor reduced MCL1 and BCL(XL)
      expression. Subsequently, we observed an increase in SAHA efficacy. Our data
      furthermore demonstrate that two different molecular mechanisms are responsible
      for the modulation of these factors. Whereas c-MYC controls transcription of MCL1
      directly, regulation of BCL(XL) was due to c-MYC's capability to regulate the
      eIF4E gene, which encodes a rate-limiting factor of eukaryotic translation. Our
      data reveal a new molecular mechanism for how c-MYC controls cell autonomous
      apoptosis and provide a rationale for a concerted inhibition of HDACs and c-MYC
      in gastric cancer.

PMID- 22456337
TI  - Cyclin-dependent kinase 5 regulates E2F transcription factor through
      phosphorylation of Rb protein in neurons.
AB  - Recent studies have shown the involvement of cyclin-dependent kinase 5 (Cdk5) in
      cell cycle regulation in postmitotic neurons. In this study, we demonstrate that
      Cdk5 and its co-activator p35 were detected in the nuclear fraction in neurons
      and Cdk5/p35 phosphorylated retinoblastoma (Rb) protein, a key protein
      controlling cell cycle re-entry. Cdk5/p35 phosphorylates Rb at the sites similar
      to those phosphorylated by Cdk4 and Cdk2. Furthermore, increased Cdk5 activity
      elevates activity of E2F transcription factor, which can trigger cell cycle re
      entry, leading to neuronal cell death. A normal Cdk5 activity in neurons did not
      induce E2F activation, suggesting that Cdk5 does not induce cell cycle re-entry
      under normal conditions. Taken together, these results indicate that Cdk5 can
      regulate cell cycle by its ability to phosphorylate Rb. Most importantly,
      increased Cdk5 activity induces cell cycle re-entry, which is especially
      detrimental for survival of postmitotic neurons.

PMID- 22456338
TI  - Weighing on autophagy: a novel mechanism for the CNS regulation of energy
      balance.

PMID- 22456339
TI  - Expression of the 49 human ATP binding cassette (ABC) genes in pluripotent
      embryonic stem cells and in early- and late-stage multipotent mesenchymal stem
      cells: possible role of ABC plasma membrane transporters in maintaining human
      stem cell pluripotency.
AB  - The 49-member human ATP binding cassette (ABC) gene family encodes 44 membrane
      transporters for lipids, ions, peptides or xenobiotics, four translation factors
      without transport activity, as they lack transmembrane domains, and one
      pseudogene. To understand the roles of ABC genes in pluripotency and
      multipotency, we performed a sensitive qRT-PCR analysis of their expression in
      embryonic stem cells (hESCs), bone marrow-derived mesenchymal stem cells (hMSCs)
      and hESC-derived hMSCs (hES-MSCs). We confirm that hES-MSCs represent an
      intermediate developmental stage between hESCs and hMSCs. We observed that 44
      ABCs were significantly expressed in hESCs, 37 in hES-MSCs and 35 in hMSCs. These
      variations are mainly due to plasma membrane transporters with low but
      significant gene expression: 18 are expressed in hESCs compared with 16 in hES
      MSCs and 8 in hMSCs, suggesting important roles in pluripotency. Several of these
      ABCs shared similar substrates but differ regarding gene regulation. ABCA13 and
      ABCB4, similarly to ABCB1, could be new markers to select primitive hMSCs with
      specific plasma membrane transporter (low)  phenotypes. ABC proteins performing
      basal intracellular functions, including translation factors and mitochondrial
      heme transporters, showed the highest constant gene expression among the three
      populations. Peptide transporters in the endoplasmic reticulum, Golgi and
      lysosome were well expressed in hESCs and slightly upregulated in hMSCs, which
      play important roles during the development of stem cell niches in bone marrow or
      meningeal tissue. These results will be useful to study specific cell cycle
      regulation of pluripotent stem cells or ABC dysregulation in complex pathologies,
      such as cancers or neurological disorders.

PMID- 22456340
TI  - Collective regulatory stock management and spatiotemporal dynamics of the food
      flow in ants.
AB  - The organization of complex societies requires constant information flow between
      individuals. The shape of the food web organizes itself according to the spatial
      distribution of the individuals and of the stocks. To understand how the spatial
      organization of the food stocks changes with the colony needs, we monitored the
      flow of radiolabeled sugar solution inside an ant nest at different degrees of
      starvation. The spatial dynamics of the food flow revealed stable patterns and
      fine-tuning regulation of the feeding process. The complex collective regulatory
      stock management task can be reproduced by a surprising simple model that
      integrates a positive and a negative feedback proportional to the number of ants
      that already received food. Spatial analysis of the food distribution showed that
      sucrose is heterogeneously stocked among individuals and also heterogeneously
      consumed. Furthermore, we observed a regular spatial structure, leading to
      centralization of the stocks: heavily loaded individuals being at the center of
      the cluster and weakly loaded individuals at its periphery. The centralization of
      both resources and information in self-organized systems might be a widespread
      phenomenon that deserves further studies.

PMID- 22456341
TI  - Binding of galectin-1 to alphaIIbbeta3 integrin triggers "outside-in" signals,
      stimulates platelet activation, and controls primary hemostasis.
AB  - Understanding noncanonical mechanisms of platelet activation represents an
      important challenge for the identification of novel therapeutic targets in
      bleeding disorders, thrombosis, and cancer. We previously reported that galectin
      1 (Gal-1), a beta-galactoside-binding protein, triggers platelet activation in
      vitro. Here we investigated the molecular mechanisms underlying this function and
      the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry
      analysis, as well as studies using blocking antibodies against the anti
      alpha(IIb) subunit ofalpha(IIb)beta(3) integrin or platelets from patients with
      Glanzmann's thrombasthenia syndrome (alpha(IIb)beta(3) deficiency), identified
      this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to
      platelets triggered the phosphorylation of beta(3)-integrin, Syk, MAPKs, PI3K,
      PLCgamma2, thromboxane (TXA(2)) release, and Ca(2+) mobilization. Not only
      soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient
      (Lgals1(-/-)) mice showed increased bleeding time (P<0.0002, knockout vs. wild
      type), which was not associated with an abnormal platelet count. Lgals1(-/-)
      platelets exhibited normal aggregation to PAR4, ADP, arachidonic acid, or
      collagen but abnormal ATP release at low collagen concentrations. Impaired
      spreading on fibrinogen and clot retraction with normal levels of
      alpha(IIb)beta(3) was also observed in Lgals1(-/-) platelets, indicating a
      failure in the "outside-in" signaling through this integrin. This study
      identifies a noncanonical mechanism, based on galectin-integrin interactions, for
      regulating platelet activation.

PMID- 22456342
TI  - Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1)
      locus enables explanation of phenotypic differences in patients with X-linked
      congenital adrenal hypoplasia.
AB  - BACKGROUND/AIM: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder
      characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It
      is caused by deletions or point mutations of the NR0B1 gene, on Xp21. AHC can be
      associated with glycerol kinase deficiency, Duchenne muscular dystrophy and
      mental retardation (MR), as part of a contiguous gene deletion syndrome. A
      synthetic probe set for multiplex ligation-dependent probe amplification analysis
      was developed to confirm and characterize NR0B1 deletions in patients with AHC
      and to correlate their genotypes with their divergent phenotypes. RESULTS: In 2
      patients, isolated AHC was confirmed, while a patient at risk for metabolic
      crisis was revealed as the deletion extends to the GK gene. A deletion extending
      to IL1RAPL1 was confirmed in both patients showing MR. Thus, a good genotype
      phenotype correlation was confirmed. CONCLUSIONS: Multiplex ligation-dependent
      probe amplification analysis is a valuable tool to detect NR0B1 and contiguous
      gene deletions in patients with AHC. It is especially helpful for IL1RAPL1
      deletion detection as no clinical markers for MR are available. Furthermore,
      multiplex ligation-dependent probe amplification has the advantage to identify
      female carriers that, depending on the deletion extension, have a high risk of
      giving birth to children with MR, AHC, glycerol kinase deficiency and Duchenne
      muscular dystrophy.

PMID- 22456343
TI  - Weight reduction alone may not be sufficient to maintain disease remission in
      obese patients with psoriasis: a randomized, investigator-blinded study.
AB  - BACKGROUND: The relative risk of psoriasis and its severity are directly related
      to the body mass index. OBJECTIVE: To investigate the effects of a hypoenergetic
      diet to maintain disease remission in obese patients. METHODS: A questionnaire
      was administered to 200 patients with moderate-to-severe chronic plaque psoriasis
      asking whether diet could influence psoriasis severity. Forty-two obese patients
      in remission (PASI improvement >=75%) for at least 12 weeks after methotrexate
      therapy were randomly assigned to receive a hypocaloric diet or free diet for 24
      weeks, and were then followed up for an additional 12 weeks. RESULTS: Most of the
      patients considered that a diet regimen could influence their psoriasis, and
      desired to enter a dietary program. Obese patients who were in disease remission
      and entered a hypocaloric diet regimen showed a significant body weight reduction
      after 12 weeks which was maintained at week 24. However, patients under
      hypocaloric and free diets did not significantly differ in the maintenance of
      psoriasis remission, with relapse observed already at week 12, but with a trend
      in favor of the intervention group. CONCLUSIONS: Body weight reduction alone may
      not be sufficient for maintaining remission of moderate-to-severe psoriasis in
      obese patients.

PMID- 22456344
TI  - Immunophenotype of Chinese patients with T-lineage acute lymphoblastic leukemia
      and its association to biological and clinical features.
AB  - BACKGROUND/AIMS: To investigate the immunophenotype of 46 Chinese patients with T
      lineage acute lymphoblastic leukemia (T-ALL) and its association with biological
      and clinical features. METHODS: 46 patients with T-ALL were immunophenotyped by
      flow cytometry, and 30 cases were also subjected to karyotype analysis by R
      banding technology. The clinical and biological characteristics of T-ALL patients
      between MyAg+ and MyAg- groups were analyzed. RESULTS: Myeloid antigen (MyAg)
      expression was documented in 41.3% of the 46 T-ALL cases. Abnormal karyotypes
      were detected in 17 out of 30 (56.7%) cases. Our data showed that the median
      lowest white blood cell (WBC) count and lowest hemoglobin level, higher CD34
      positivity, and a lower proportion of patients with splenomegaly were found to be
      correlated with MyAg+ T-ALL. No statistical difference was noted in the complete
      remission (CR) rate, relapse rate, induction death rate or total death rate among
      MyAg+ and MyAg- patients. In our cohort, none of the antigens tested affected the
      CR rate after the first induction. CONCLUSION: Our results indicate that MyAg
      expression in patients with T-ALL was not associated with adverse presenting
      clinical and biological features as well as response to induction treatment. The
      expression of surface antigens had no impact on initial chemotherapy CR
      achievement.

PMID- 22456345
TI  - Identification of new biomarkers for Down's syndrome in maternal plasma.
AB  - Using ProteinChip Technology (SELDI TOF MS), the maternal plasma of 53
      chromosomally-normal control and 28 Down's syndrome affected pregnancies was
      profiled between 10 and 20 weeks' gestation. Preliminary studies demonstrated two
      distinct phases of changes in protein expression, the first at 10-14 weeks and
      second at 14-20 weeks. Using this data, analysis of the 10-14 weeks' plasma
      samples (Down's syndrome n=13, control n=20) showed the presence of a protein of
      mass 100.3 kDa that was elevated in the Down's syndrome group compared to the
      controls (p<0.002). This protein was further isolated using SAX Q-spin columns
      and identified using QTOF MS and Western blotting as being plasma protease C1
      inhibitor. Analysis of the 14-20 week cohort demonstrated changes in protein
      expression of three additional proteins. Two of these proteins were found to be
      up-regulated (serum amyloid P-component, p<0.004 and transthyretin, p<0.006) and
      complement C3-alpha chain was observed to be down-regulated (p<0.0005). The
      identification of these biomarkers in maternal plasma and their potential to
      improve current Down's syndrome screening are discussed.

PMID- 22456346
TI  - Reevaluation of the association of seven candidate genes with blood pressure and
      hypertension: a replication study and meta-analysis with a larger sample size.
AB  - To obtain evidence for blood pressure (BP) trait association, we conducted an
      association study of selected candidate gene variants. In Japan, a total of
      19,426 individuals underwent testing for genetic associations with systolic BP
      (SBP)/diastolic BP (DBP) and 9271 individuals (3460 cases and 5811 controls)
      underwent testing for genetic associations with dichotomous hypertension.
      Association with seven notable candidate genes was tested, namely, ACE, ADD1,
      ADRB2, AGT, CYP11B2, GNB3 and NOS3, followed by a joint meta-analysis involving
      previously reported multi-study populations, including >20,000 individuals (for
      SBP/DBP) and >17,000 individuals (for hypertension). BP trait associations at two
      loci (AGT rs699 and CYP11B2 rs1799998) were consistently replicated in the
      Japanese association study and joint meta-analysis involving the populations
      described above. Hypertension association reached genome-wide significance for
      the two variants, specifically, P=7.3 * 10(-10) for AGT rs699 and P=3.9 * 10(-8)
      for CYP11B2 rs1799998. In our study panels, the most significant association was
      found for CYP11B2 rs1799998 with all three BP traits: P=1.5 * 10(-5) for SBP,
      P=1.8 * 10(-5) for DBP and P=2.3 * 10(-5) for hypertension. A suggestive
      association with SBP (P=0.042), DBP (P=0.01) and hypertension (P=1.4 * 10(-5))
      was also detected for ACE rs4340 (a proxy for ACE D/I polymorphism) in the joint
      meta-analysis. Our data provide evidence for true BP trait associations with two
      candidate gene variants. These variants were not identified in the previous
      genome-wide association studies, presumably because they did not reach a given
      threshold in the discovery stage. Thus, certain variants in genes with clinical
      and physiological relevance are likely to account for a portion of BP variance in
      the general population and are worth following up via a target gene approach.

PMID- 22456347
TI  - The ratio of observed to predicted left ventricular mass is independently
      associated with increased cardiovascular events in patients with chronic kidney
      disease.
AB  - A condition involving the growth of the myocardium that exceeds hemodynamic needs
      has been reported and called as inappropriate left ventricular mass (LVM). The
      appropriateness of LVM can be estimated by the ratio of observed LVM to predicted
      LVM. The excessive growth of LVM is frequently noted in patients with chronic
      kidney disease (CKD). This study is designed to assess whether the ratio of
      observed to predicted LVM is a useful prognostic indicator of cardiovascular
      events in patients with moderate to advanced CKD. We consecutively enrolled 485
      patients with CKD stages 3-5 from our Outpatient Department of Internal Medicine.
      Inappropriate LVM was defined as observed LVM more than 28% greater than the
      predicted value. The relative risk of cardiovascular events was analyzed by Cox
      regression methods. There was a significant trend for a stepwise increase in the
      observed/predicted LVM ratio (P<0.001) and the prevalence of inappropriate LVM
      (P=0.003) corresponding to advances in CKD stages. In the multivariate analysis,
      old age, a history of coronary artery disease, congestive heart failure, atrial
      fibrillation, wide pulse pressure, decreased serum albumin and hemoglobin levels,
      left atrial diameter >4.7 cm and increased observed/predicted LVM were
      independently associated with increased cardiovascular events. Our findings show
      that increased observed/predicted LVM is independently associated with adverse
      cardiovascular outcomes in patients with CKD stages 3-5.

PMID- 22456348
TI  - High-protein-low-carbohydrate diet during pregnancy alters maternal plasma amino
      acid concentration and placental amino acid extraction but not fetal plasma amino
      acids in pigs.
AB  - A high protein-low-carbohydrate diet during pregnancy can cause intra-uterine
      growth restriction. However, its impact during pregnancy on maternal, umbilical
      and fetal plasma amino acid (AA) profiles is unknown. A maternal high-protein (30
      %)-low-carbohydrate (HP-LC) diet was compared with isoenergetic standard (12.1 %
      crude protein; ST) and low-protein (6.5 %)-high-carbohydrate (LP-HC) diets fed to
      nulliparous pregnant sows to examine changes in AA concentrations in maternal,
      venous and arterial umbilical and fetal plasma in mid and late pregnancy. At 64
      and 94 days of pregnancy (dp), sows underwent Caesarean section, and maternal,
      umbilical and fetal plasma samples were collected. The HP-LC diet mainly affected
      maternal plasma AA concentrations. Plasma concentrations of Ile and Val were
      increased and those of Ala, Glu and Gly were decreased (P <= 0.05) in HP-LC
      compared with ST sows at 64 and 94 dp. The LP-HC diet decreased fetal plasma Glu
      concentration compared with the ST diet at 94 dp. Substantial AA catabolism was
      reflected by increased (P <= 0.05) maternal and fetal plasma urea concentrations
      with the HP-LC compared with the ST and LP-HC diets at 94 dp. Fractional
      placental extraction of Val was higher whereas those of Ala, Gln and Glu were
      lower in the HP-LC compared with the ST sows at 64 and 94 dp (P <= 0.05). Reduced
      fetal mass at 94 dp was accompanied by reduced fetal extraction of Lys and Pro in
      the HP-LC group (P <= 0.05). In conclusion, a maternal HP-LC diet during
      pregnancy altered maternal plasma composition of many AA and modified placental
      AA extraction to compensate for imbalanced maternal nutrient intake.

PMID- 22456350
TI  - Developmental biology: Re-evaluating gut insulin instinct.

PMID- 22456349
TI  - Molecular phylogenetics: principles and practice.
AB  - Phylogenies are important for addressing various biological questions such as
      relationships among species or genes, the origin and spread of viral infection
      and the demographic changes and migration patterns of species. The advancement of
      sequencing technologies has taken phylogenetic analysis to a new height.
      Phylogenies have permeated nearly every branch of biology, and the plethora of
      phylogenetic methods and software packages that are now available may seem
      daunting to an experimental biologist. Here, we review the major methods of
      phylogenetic analysis, including parsimony, distance, likelihood and Bayesian
      methods. We discuss their strengths and weaknesses and provide guidance for their
      use.

PMID- 22456351
TI  - Discussion: are pfannenstiel scars a boon or a curse for DIEP flap breast
      reconstructions?

PMID- 22456352
TI  - Strategies for recognizing and managing intraoperative venous congestion in
      abdominally based autologous breast reconstruction.
AB  - BACKGROUND: Despite common superficial venous system dominance of the abdominal
      wall, the majority of transverse rectus abdominis musculocutaneous (TRAM)/deep
      inferior epigastric perforator (DIEP) flaps drain adequately, due to
      communicating veins with the deep system. In cases where such connections are
      inadequate, it is necessary for the surgeon to correctly recognize resultant
      congestion as an intrinsic flap issue, and treat it intraoperatively. METHODS: A
      retrospective analysis of 1201 consecutive TRAM/DIEP free flaps over a 5-year
      period was performed. All cases of inadequate venous outflow not due to technical
      anastomotic problems or venous thrombosis were identified and analyzed. RESULTS:
      From a cohort of 1201 patients undergoing free TRAM and DIEP flap breast
      reconstruction, 11 (0.9 percent) exhibited intraoperative congestion due to
      persistent superficial venous system dominance, despite patent deep vein
      anastomosis. Most commonly (five flaps), anastomosis of the superficial inferior
      epigastric vein (SIEV) to a proximally dissected vena comitans of the flap deep
      inferior epigastric vein system (DIEV) was performed; thus, a superficial to deep
      venous loop was created within the flap. Intraoperative salvage rate was 100
      percent. CONCLUSIONS: In this series, intraoperative congestion is most commonly
      due to a superficially dominant flap. In such flaps, the deep venous anastomosis
      is patent, and yet adequate venous drainage cannot be achieved due to the lack of
      communicating vessels between the two systems, or due to inadequate perforator
      selection. Anastomosis of the SIEV to a proximally dissected vena comitans of the
      DIEV on the flap was performed most commonly in our series. This allows
      anastomosis of two veins in close proximity, and avoidance of using a second
      recipient vein. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22456353
TI  - Implant-based, two-stage breast reconstruction in the setting of radiation
      injury:  an outcome study.
AB  - BACKGROUND: More women with breast cancer who either have already had radiation
      therapy or will be getting radiation therapy as part of their treatment protocol
      are now seeking implant-based breast reconstruction. The literature on the
      success of this type of reconstruction in the setting of radiation injury is
      mixed. METHODS: A single reconstructive surgeon's experience over a 10-year
      period with implant-based, two-stage breast reconstruction was retrospectively
      examined. A total of 267 breasts in 194 patients were included in the study and
      divided into three groups. Reconstruction was performed for breasts that had no
      radiation exposure (n = 218), radiation exposure before mastectomy/reconstruction
      (n = 32), or radiation exposure after mastectomy and first-stage reconstruction
      but before completion of the second stage of reconstruction (n = 17). Age, follow
      up time, history (of diabetes, smoking, and chemotherapy), body mass index, and
      expander volume were recorded. Logistical regression analysis was performed for
      major reoperative complications following the reconstruction. RESULTS: Radiation
      exposure before reconstruction resulted in a 43.8 percent complication rate,
      during reconstruction had a 41.2 percent complication rate, and no radiation
      exposure had a 13.8 percent complication rate. The most common complication in
      both radiation groups was wound dehiscence, but there were also a significant
      number of patients who had failure of expansion. In addition, smoking
      significantly influenced the occurrence of complications. CONCLUSIONS: Radiation
      therapy for the treatment of breast cancer significantly increased the incidence
      of major, reoperative complications in implant-based, two-stage breast
      reconstruction. Despite this high rate, however, in the present study, 80 percent
      of patients with major complications went on to complete their breast
      reconstructions with either implants or autogenous tissue. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 22456354
TI  - Regulation of adipogenesis by lymphatic fluid stasis:  part I. Adipogenesis,
      fibrosis, and inflammation.
AB  - BACKGROUND: Although fat deposition is a defining clinical characteristic of
      lymphedema, the cellular mechanisms that regulate this response remain unknown.
      The goals of this two-part study were to determine the effect of lymphatic fluid
      stasis on adipogenesis and inflammation (part I) and how these changes regulate
      the temporal and spatial expression of fat differentiation genes (part II).
      METHODS: Adult female mice underwent tail lymphatic ablation and were euthanized
      6 weeks after surgery (n = 20). Fat deposition, fibrosis, and inflammation were
      then analyzed in the regions of the tail exposed to lymphatic fluid stasis as
      compared with normal lymphatic flow. RESULTS: Lymphatic fluid stasis in the tail
      resulted in significant subcutaneous fat deposition, with a 2-fold increase in
      fat thickness (p < 0.01). In addition, lymphatic stasis was associated with
      subcutaneous fat fibrosis and collagen deposition. Adipogenesis in response to
      lymphatic fluid stasis was associated with a marked mononuclear cell inflammatory
      response (5-fold increase in CD45 cells; p < 0.001). In addition, the authors
      noted a significant increase in the number of monocytes/macrophages as identified
      by F4/80 immunohistochemistry (p < 0.001). CONCLUSIONS: The mouse-tail model has
      pathologic findings that are similar to clinical lymphedema, including fat
      deposition, fibrosis, and inflammation. Adipogenesis in response to lymphatic
      fluid stasis closely resembles this process in obesity. This model therefore
      provides an excellent means with which to study the molecular mechanisms that
      regulate the pathophysiology of lymphedema.

PMID- 22456355
TI  - Discussion:  regulation of adipogenesis by lymphatic fluid stasis:  part I.
      Adipogenesis, fibrosis, and inflammation.

PMID- 22456356
TI  - Regulation of adipogenesis by lymphatic fluid stasis: part II. Expression of
      adipose differentiation genes.
AB  - BACKGROUND: Although fat deposition is a defining clinical characteristic of
      lymphedema, the cellular mechanisms that regulate this response remain unknown.
      The goal of this study was to determine how lymphatic fluid stasis regulates
      adipogenic gene activation and fat deposition. METHODS: Adult female mice
      underwent tail lymphatic ablation and were euthanied at 1, 3, or 6 weeks
      postoperatively (n = 8 per group). Samples were analyzed by immunohistochemistry
      and Western blot analysis. An alternative group of mice underwent axillary
      dissections or sham incisions, and limb tissues were harvested 3 weeks
      postoperatively (n = 8 per group). RESULTS: Lymphatic fluid stasis resulted in
      significant subcutaneous fat deposition and fibrosis in lymphedematous tail
      regions (p < 0.001). Western blot analysis demonstrated that proteins regulating
      adipose differentiation including CCAAT/enhancer-binding protein-alpha and
      adiponectin were markedly up-regulated in response to lymphatic fluid stasis in
      the tail and axillary models. Expression of these markers increased in edematous
      tissues according to the gradient of lymphatic stasis distal to the wound.
      Immunohistochemical analysis further demonstrated that adiponectin and peroxisome
      proliferator-activated receptor-gamma, another critical adipogenic transcription
      factor, followed similar expression gradients. Finally, adiponectin and
      peroxisome proliferator-activated receptor-gamma expression localized to a
      variety of cell types in newly formed subcutaneous fat. CONCLUSIONS: The mouse
      tail model of lymphedema demonstrates pathologic findings similar to clinical
      lymphedema, including fat deposition and fibrosis. The authors show that
      lymphatic fluid stasis potently up-regulates the expression of fat
      differentiation markers both spatially and temporally. These studies elucidate
      mechanisms regulating abnormal fat deposition in lymphedema pathogenesis and
      therefore provide a basis for developing targeted treatments.

PMID- 22456357
TI  - Deferoxamine enhances the vascular response of bone regeneration in mandibular
      distraction osteogenesis.
AB  - BACKGROUND: Bone regeneration during distraction osteogenesis is intricately
      associated with an enhanced vascular response. Augmenting this response may offer
      considerable clinical advantages such as optimizing the quality of regenerate
      formation, decreasing lengthy consolidation periods, or increasing regenerate
      size and distance. Using deferoxamine, an angiogenic transcriptional activator,
      the authors posit that substantial increases in vascular volume beyond the normal
      response to mechanical distraction can be quantified with micro-computed
      tomography after vessel perfusion during mandibular distraction osteogenesis.
      METHODS: Two groups of Sprague-Dawley rats (n = 12) underwent external fixator
      placement, mandibular osteotomy, and 5.1-mm distraction. During distraction, the
      experimental group (n = 6) was treated with deferoxamine injections into the
      distraction gap. After consolidation, the animals were perfused and imaged with
      micro-computed tomography. Vascular radiomorphometrics were calculated and
      statistical comparison was conducted with the independent samples t test. A value
      of p <= 0.05 was considered statistically significant. RESULTS: A 40 percent
      statistically significant increase in the number of vessels (0.82 vessels/mm
      versus 1.15 vessels/mm; p < 0.012) and a complementary decrease in the space
      between vessels (1.18 mm versus 0.86 mm; p < 0.012) were calculated in the
      experimental regenerate when compared with controls. This robust increase in
      vascularity could also be readily observed with micro-computed tomographic image
      reconstruction. Gross examination revealed a denser regenerate in the
      deferoxamine-injected group that is clearly illustrated with Faxitron
      radiography. CONCLUSION: The authors' study quantifies the ability of
      deferoxamine to augment the vascular response of mandibular distraction
      osteogenesis and establishes correlations between this therapeutic enrichment and
      enhanced regenerate formation.

PMID- 22456358
TI  - Subcutaneous injections of platelet-rich plasma into skin flaps modulate
      proangiogenic gene expression and improve survival rates.
AB  - BACKGROUND: Flap necrosis remains a major complication of reconstructive surgery.
      To improve skin flap survival, various treatments with vasodilators, antiplatelet
      drugs, or the local administration of growth factors have been performed.
      However, the sufficient prevention of skin necrosis is not well established.
      Platelet-rich plasma has been used as an autologous factor and includes various
      growth factors. The authors evaluated whether or not platelet-rich plasma can
      improve skin flap survival in an experimental rat model. METHODS: Cranially based
      dorsal cutaneous flaps were elevated in 48 rats. The animals received
      subcutaneous injections of either platelet-rich plasma (100 MUl) or platelet-poor
      plasma (100 MUl). The rats were divided into three groups: the platelet-rich
      plasma group (n = 16), the platelet-poor plasma group (n = 16), and the
      nontreatment group (n = 16). Flap survival was measured and histologic specimens
      were collected on day 7. Real-time polymerase chain reaction specimens were
      collected after 8 hours, 24 hours, 3 days, and 7 days. RESULTS: Platelet-rich
      plasma significantly improved flap survival rates (61.2 percent) compared with
      the platelet-poor plasma treatment (35.8 percent) and nontreatment groups (28.0
      percent). A histologic analysis showed that significantly fewer inflammatory
      cells and an increased blood vessel density were observed in the platelet-rich
      plasma rats versus the platelet-poor plasma or nontreatment rats. In addition,
      platelet-rich plasma treatment significantly increased the mRNA levels of
      vascular endothelial growth factor and platelet-derived growth factor.
      CONCLUSION: Platelet-rich plasma modulates the genes involved in angiogenesis and
      improves skin flap survival.

PMID- 22456359
TI  - Hemiface allotransplantation in the mouse.
AB  - Rat models of experimental face transplantation have been widely used to study
      vascularized composite tissue allotransplantation. Because the mouse represents a
      superior species for vascularized composite tissue allotransplantation research,
      the authors developed a novel surgical technique with which to perform hemiface
      transplantation in mice. BALB/c hemifacial grafts were transplanted into BALB/c
      (group 1) or C57BL6 (group 2) recipients (n = 6 per group). Myocutaneous hemiface
      grafts including a vascular pedicle consisting of the common carotid artery and
      the external jugular vein were retrieved using superfine microsurgical
      instruments. The graft was transplanted orthotopically and revascularized using
      the recipient common carotid artery and external jugular vein for anastomosis
      applying a non-suture cuff technique. After an initial learning curve, the
      surgical procedure was performed with a constant and high success rate (78
      percent). Operating time was comparable in all groups and lasted 120 +/- 15
      minutes for the donor and 150 +/- 12 minutes for the recipient. All syngeneic
      grafts survived long term (>100 days). Allograft rejection in group 2 occurred
      within 14 +/- 2 days. Hematoxylin and eosin stains of syngeneic grafts revealed
      unaltered muscle and skin histology. Allogeneic grafts gradually showed distinct
      rejection patterns progressing with time and similar to those observed after
      human face transplantation. This is the first description of a mouse hemiface
      allotransplantation model. The microsurgically demanding procedure may be used to
      investigate basic immunology and rejection and to address questions related to
      nerve regeneration in reconstructive face transplantation.

PMID- 22456360
TI  - Perforator-supercharged occipitocervicopectoral flaps for lower face and neck
      reconstruction.
AB  - BACKGROUND: The occipitocervicopectoral flap has a local skin pedicle in the
      occipital region, with the distal portion of the flap in the pectoral region. One
      disadvantage of the occipitocervicopectoral flap is its limited flap length. To
      overcome this disadvantage, a perforator supercharging technique was applied to
      enlarge the original flap length. The aims of this study are to present a
      clinical application of the perforator-supercharged occipitocervicopectoral flap
      for face and neck reconstruction and to discuss a perforator supercharging
      technique and perforator anatomy. METHODS: All perforator-supercharged
      occipitocervicopectoral flaps that were used for face and neck reconstructions
      were analyzed retrospectively. RESULTS: In all nine cases, the second internal
      mammary artery perforator was attached at the end of the occipitocervicopectoral
      flap and supercharged with the contralateral recipient facial artery vessels. The
      average flap size was 22.6 * 6.2 cm, without any flap loss. It was possible to
      cover a large defect extending to bilateral sides with thin and pliable local
      skin tissue. All patients were satisfied with functional and aesthetic results
      achieved postoperatively after 6 months. CONCLUSIONS: The internal mammary artery
      perforator-supercharged occipitocervicopectoral flap can be considered a type of
      bipedicle perforator flap and can provide reliable flap vascularity. By using a
      perforator supercharging technique, we can adjust and enlarge the flap length
      tailored to the defect. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22456361
TI  - Metrics of cellular and vascular infiltration of human acellular dermal matrix in
      ventral hernia repairs.
AB  - BACKGROUND: Human acellular dermal matrix is used for ventral hernia repair, as
      it resists infection and remodels by means of surrounding tissue. However, the
      tissue source and impact of basement membrane on cell and vessel infiltration
      have not been determined. The authors hypothesized that musculofascia would be
      the primary tissue source of cells and vessels infiltrating into human acellular
      dermal matrix and that the basement membrane would inhibit infiltration. METHODS:
      Fifty-six guinea pigs underwent inlay human acellular dermal matrix ventral
      hernia repair with the basement membrane oriented toward or away from the
      peritoneum. At postoperative weeks 1, 2, or 4, repair sites were completely
      excised. Histologic and immunohistochemical analyses were performed to quantify
      cell and vessel density within repair-site zones, including interface (lateral,
      beneath musculofascia) and center (beneath subcutaneous fat) zones. Cell and
      vessel quantities were compared as functions of zone, basement membrane
      orientation, and time. RESULTS: Cellular and vascular infiltration increased over
      time universally. The interface demonstrated greater mean cell density than the
      center (weeks 1 and 2, p = 0.01 and p < 0.0001, respectively). Cell density was
      greater with the basement membrane oriented toward the peritoneum at week 4 (p =
      0.02). The interface zone had greater mean vessel density than the center zone at
      week 4 (p < 0.0001). Orienting the basement membrane toward the peritoneum
      increased vessel density at week 4 (p = 0.0004). CONCLUSIONS: Cellular and
      vascular infiltration into human acellular dermal matrix for ventral hernia
      repairs was greater from musculofascia than from subcutaneous fat, and the
      basement membrane inhibited cellular and vascular infiltration. Human acellular
      dermal matrix should be placed adjacent to the best vascularizing tissue to
      improve fibrovascular incorporation.

PMID- 22456362
TI  - The sympathetic innervation of the human foot.
AB  - BACKGROUND: The sympathetic innervation of the hand was demonstrated using
      formaldehyde staining techniques in the 1990s and provides a basis for both
      medical (botulinum toxin type A) and surgical (sympathectomy) therapeutic
      approaches. This research investigates the sympathetic innervation of the human
      foot using tyrosine hydroxylase immunohistochemistry. METHODS: With institutional
      review board approval, six freshly amputated lower extremities had arterial,
      venous, and peripheral nerve biopsies obtained at the distal leg, ankle, and
      forefoot levels. Tibial, peroneal, sural, and saphenous nerves were processed
      immediately for immunohistochemical staining using an anti-tyrosine hydroxylase
      antibody, for light and electron microscopy evaluation. Qualitative assessments
      noted the presence or absence of tyrosine hydroxylase-positive fibers in artery,
      vein, and peripheral nerve. Within the nerve, location of the tyrosine
      hydroxylase staining was noted. RESULTS: The presence of tyrosine hydroxylase
      positive material was identified in each artery, vein, and nerve examined at each
      level of the foot and ankle. For the artery, the staining was in the adventitia,
      and rarely in the media of the vessel wall. There were clear entry points into
      the artery from the connective tissue. For the vein, the staining was more evenly
      distributed but to a lesser intensity than in the artery. Within each nerve at
      the proximal levels, the staining was diffusely throughout the fascicles, with
      clear sites of fibers leaving the periphery. CONCLUSIONS: It is concluded that
      (1) sympathetic innervation of the foot arrives along each peripheral nerve, (2)
      the vessels already contain sympathetic innervation at the level of the ankle,
      and (3) the sympathetic innervation of the foot is extensive.

PMID- 22456363
TI  - PEDOT electrochemical polymerization improves electrode fidelity and sensitivity.
AB  - BACKGROUND: The goal of the authors is to restore fine motor control and
      sensation for high-arm amputees. They developed a regenerative peripheral nerve
      interface with the aim of attaining closed loop neural control by integrating
      directly with the amputee's residual motor and sensory peripheral nerves. PEDOT,
      poly(3,4-ethylenedioxythiophene), has both electrical and ionic conduction
      characteristics. This hybrid character could help bridge the salutatory
      conduction of the nervous system to an electrode. The purpose of this study was
      to determine whether electrodes polymerized with PEDOT have improved ability to
      both record and stimulate peripheral nerve action potentials. METHODS: Impedance
      spectroscopy and cyclic voltammetry were performed on electrodes before and after
      polymerization to measure electrode impedance and charge capacity. Both recording
      needle and bipolar stimulating electrodes were polymerized with PEDOT. Plain and
      PEDOT electrodes were tested using rat (n = 18) in situ nerve conduction studies.
      The peroneal nerve was stimulated using a bipolar electrode at multiple locations
      along the nerve. Action potentials were measured in the extensor digitorum longus
      muscle. RESULTS: Bench testing showed PEDOT electrodes had a higher charge
      capacity and lower impedance than plain electrodes, indicating significantly
      improved electrode fidelity. Nerve conduction testing indicated a significant
      reduction in the stimulus threshold for both PEDOT recording and PEDOT
      stimulatory electrodes when compared with plain electrodes, indicating an
      increase in sensitivity. CONCLUSIONS: PEDOT electrochemical polymerization
      improves electrode fidelity. Electrodes that have been electropolymerized with
      PEDOT show improved sensitivity when recording or stimulating action potentials
      at the tissue-electrode interface.

PMID- 22456364
TI  - Genetic and epigenetic influences of twins on the pathogenesis of
      craniosynostosis:  a meta-analysis.
AB  - BACKGROUND: The pathoetiology of craniosynostosis is not well understood. It
      likely results from a combination of genetic and epigenetic phenomena, such as
      intrauterine constraint from multiple gestations. Information on craniosynostosis
      in twins is limited to case reports and series. The authors conducted a
      systematic review and meta-analysis of the literature to elucidate the genetic
      and nongenetic influences of twins on the pathogenesis of craniosynostosis.
      METHODS: PubMed and Ovid databases were reviewed for the key terms
      "craniosynostosis and twins." Data analyzed included demographical information,
      incidence rates, concordance, and phenotypic variability. Risk factors for
      craniosynostosis, concordance, and phenotypic variability were assessed by
      univariate and multivariate analyses. A case series was presented. RESULTS: Data
      were extracted from 34 journal articles, including the authors' five patients,
      and representing a total of 199 twins with craniosynostosis. Twinning was 2.62
      times greater in patients with craniosynostosis (6.29 percent) compared with
      unaffected controls (2.4 percent; p < 0.0001). Boys were affected more than girls
      (65.30 versus 34.70 percent, respectively; p < 0.0001). Monozygotic concordance
      rates were greater than dizygotic (60.90 versus 5.30 percent, respectively; p <
      0.0001) but were not 100 percent. Phenotypic variability was present in 62
      percent of monozygotic twin sets (p < 0.05). CONCLUSIONS: Increased concordance
      rates among monozygotic compared with dizygotic twins confirm the genetic role of
      twins on craniosynostosis. Evidence to support the epigenetic influence of
      twinning on the pathogenesis of craniosynostosis includes the elevated incidence
      of twins among a craniosynostotic population compared with unaffected twins in
      the general population and male gender predominance, as well as monozygotic
      phenotypic variability and discordance. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Risk, IV.

PMID- 22456365
TI  - Conjoined twin separation:  lessons learned.
AB  - BACKGROUND: The separation of conjoined twins presents a unique challenge to many
      pediatric surgical specialties. A multidisciplinary approach is essential for
      successful twin separation, and plastic surgeons are critical members of this
      surgical team when soft-tissue requirements preclude simple closure. METHODS: In
      this article, the authors review multiple techniques available to plastic
      surgeons for providing adequate soft-tissue coverage in this unique clinical
      situation and present lessons learned from their experience at The Children's
      Hospital of Philadelphia with seven conjoined twin separations performed between
      the years 1980 and 2007. RESULTS: Successful separation was accomplished in six
      of the seven conjoined twin pairs, expander complications requiring reoperation
      occurred in three twin pairs, and skin grafting was required because of
      insufficient expansion in two twin pairs. The techniques found to be critical to
      successful separation include maximal extracavitary tissue expansion with smooth
      wall remote port tissue expanders, protection of expanded skin through pressure
      reducing strategies, fluorescein vascular territory mapping, the use of frozen
      banked autogenous skin for salvage, and the use of supplemental nutritional
      support. CONCLUSIONS: The overall success of conjoined twin separation depends on
      the experience and preparedness of the treating team and the resources available
      at the pediatric specialty center. Multiple techniques are available to plastic
      surgeons to optimize success in this challenging clinical situation. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 22456366
TI  - Discussion:  prospective outcome study of 360 patients treated with liposuction,
      lipoabdominoplasty, and abdominoplasty.

PMID- 22456367
TI  - A measurement system for evaluation of shape changes and proportions after
      cosmetic breast surgery.
AB  - BACKGROUND: Evaluation of changes in breast shape, particularly "upper pole
      fullness," "breast projection," and "bottoming out," has been made difficult by
      the lack of an accepted definition of these entities and no standardized system
      for measurements and comparison. Three-dimensional imaging is impractical for
      most surgeons and limited in providing evidence-based assessments. METHODS: Using
      standardized photographs and computer imaging software to match size and
      orientation, breast shape and size are measured and compared before and after
      cosmetic breast surgery. Practical landmarks and analysis allow assessment of
      results using standard two-dimensional frontal and lateral views. A horizontal
      plane at the level of maximum postoperative breast projection and a vertical
      plane dropped from the sternal notch serve as the reference planes. Breast
      projection, upper pole projection, lower pole level, nipple level, lower pole
      width, breast parenchymal ratio, and lower pole ratio (a measure of the boxiness
      of the lower pole) are defined and measured. RESULTS: These simple measurements
      may be easily used by surgeons to evaluate the effectiveness of their techniques
      in breast augmentation, mastopexy, augmentation/mastopexy, and reduction. Claims
      regarding changes in breast projection, upper pole projection, and breast mound
      elevation may be objectively evaluated. CONCLUSION: This measurement system
      provides a highly practical means with which to quantitate breast shape changes
      after surgery and assess surgical results using well-defined references. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 22456368
TI  - Discussion:  a measurement system for evaluation of shape changes and proportions
      after cosmetic breast surgery.

PMID- 22456369
TI  - Blindness following cosmetic injections of the face.
AB  - BACKGROUND: Complications following facial cosmetic injections have recently
      heightened awareness of the possibility of iatrogenic blindness. The authors
      conducted a systematic review of the available literature to provide the best
      evidence for the prevention and treatment of this serious eye injury. METHODS:
      The authors included in the study only the cases in which blindness was a direct
      consequence of a cosmetic injection procedure of the face. RESULTS: Twenty-nine
      articles describing 32 patients were identified. In 15 patients, blindness
      occurred after injections of adipose tissue; in the other 17, it followed
      injections of various materials, including corticosteroids, paraffin, silicone
      oil, bovine collagen, polymethylmethacrylate, hyaluronic acid, and calcium
      hydroxyapatite. CONCLUSIONS: Some precautions may minimize the risk of
      embolization of filler into the ophthalmic artery following facial cosmetic
      injections. Intravascular placement of the needle or cannula should be
      demonstrated by aspiration before injection and should be further prevented by
      application of local vasoconstrictor. Needles, syringes, and cannulas of small
      size should be preferred to larger ones and be replaced with blunt flexible
      needles and microcannulas when possible. Low-pressure injections with the release
      of the least amount of substance possible should be considered safer than bolus
      injections. The total volume of filler injected during the entire treatment
      session should be limited, and injections into pretraumatized tissues should be
      avoided. Actually, no safe, feasible, and reliable treatment exists for
      iatrogenic retinal embolism. Nonetheless, therapy should theoretically be
      directed to lowering intraocular pressure to dislodge the embolus into more
      peripheral vessels of the retinal circulation, increasing retinal perfusion and
      oxygen delivery to hypoxic tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

PMID- 22456370
TI  - Beyond working hours:  part I. Genesis and current difficulties.
AB  - The roots of the working hours mandate and controversy are outlined, the effect
      on resident education is described, and the service versus education equation is
      defined.

PMID- 22456371
TI  - Training the contemporary surgeon-scientist.

PMID- 22456375
TI  - Anaplastic large cell lymphoma and breast implants:  five Australian cases.
AB  - BACKGROUND: There has never been a convincing association between breast implants
      and breast malignancy. A total of 42 cases of non-Hodgkin's lymphoma of the
      breast associated with implant capsules have been reported. The majority of the
      patients have anaplastic large cell lymphoma of T-cell origin. These lymphoma
      types have less frequently been observed in women without implants. METHODS: The
      senior author (H.R.W.) diagnosed and treated two women with anaplastic large cell
      lymphoma in a short period of time. After this, the authors were contacted by
      other surgeons in Australia who had treated similar cases. RESULTS: The authors
      report five new cases of anaplastic large cell lymphoma associated with breast
      implants. There is an apparent spectrum of disease, with some cases pursuing an
      aggressive clinical course, although most have experienced a good prognosis. Both
      saline and silicone implants are implicated. All implant shells were textured.
      CONCLUSIONS: Textured surface implants only became widely used in the 1990s and
      therefore were not significantly represented in the large cohort studies of
      breast implant safety undertaken in the early 1990s. The diagnosis of anaplastic
      large cell lymphoma in the breast needs to be considered in patients,
      particularly those presenting with a periprosthetic seroma 6 months or more after
      breast implant insertion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

PMID- 22456376
TI  - Assessment of zonal perfusion using intraoperative angiography during abdominal
      flap breast reconstruction.
AB  - BACKGROUND: There is an ongoing debate about the reliability of various lower
      abdominal flaps for breast reconstruction. The authors evaluate in vivo perfusion
      of these flaps to objectively determine which techniques and which skin island
      zones had better perfusion. METHODS: A prospective study was performed on 77
      single-pedicle breast reconstructions [pedicled transverse rectus abdominis
      muscle (TRAM), n = 22; muscle-sparing free TRAM, n = 37; deep inferior epigastric
      perforator (DIEP), n = 18]. Perfusion was measured intraoperatively using
      indocyanine green angiography following flap harvest and before transfer. Flow
      quantification was performed at 12 standardized data points in each of the four
      zones of the skin island. Patient risk factors for flap ischemia were assessed,
      perfusion was quantified, and comparisons were made between the various flaps and
      between zones. RESULTS: Mean perfusion was significantly higher in the 37 free
      muscle-sparing flaps (24.9) and the 18 DIEP flaps (21.8) when compared with the
      22 pedicled TRAM flaps (19.6) (p < 0.001). Zones I and IV had significantly
      higher and lower perfusion, respectively (28.4 versus 13.9), when compared with
      the other zones. There was no significant difference in perfusion between zones
      II and III (20.6 versus 21.6). Differences in flap flow were significant (p <
      0.001) independent of zonal differences. CONCLUSIONS: The authors demonstrated
      objectively that lower abdominal free flaps based on the inferior epigastric
      system have better perfusion when compared with pedicled TRAM flaps. There is no
      appreciable difference in perfusion between zones II and III; however, it is
      likely related to the perforator location and dominance. Clinical correlation
      between these absolute perfusion values and flap viability is required. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 22456377
TI  - Radiation-induced craniofacial bone growth inhibition: acute and long-term
      effects on bone histopathology with and without cytoprotection.
AB  - BACKGROUND: The authors previously established an animal model of radiation
      induced craniofacial bone growth inhibition and demonstrated the effectiveness of
      cytoprotection in preserving growth using amifostine, but the mechanism is
      unclear. The objective of this study was to investigate the acute and long-term
      histopathologic effects of single-dose orthovoltage irradiation on craniofacial
      bone with and without cytoprotection. METHODS: Sixty infant New Zealand White
      rabbits (7-week-old) were randomized into three groups (n = 20 per group): group
      1, 0-Gy, sham irradiation; group 2, 35-Gy single-dose orthovoltage irradiation;
      and group 3, cytoprotection with amifostine before irradiation. Orbitozygomatic
      complex bone was harvested from animals 12 hours after irradiation and at
      skeletal maturity (21 weeks of age). Histologic parameters measured included
      native bone cell (osteoblast, osteoclast, and osteocyte) populations, periosteal
      proliferation indices (MIB-1 stains), bone turnover rates [triple fluorochromes:
      tetracycline administered at 7 weeks of age (before irradiation), alizarin
      complexone at 12 weeks, and calcein at 16 weeks of age], and endosteal space
      fibrosis levels. RESULTS: Orthovoltage irradiation significantly (p < 0.05)
      reduced osteoblast and osteoclast counts 12 hours after irradiation (age, 7
      weeks) with or without pretreatment with amifostine but had no effect on
      osteocyte populations. Long-term analysis at age 21 weeks demonstrated
      significantly (p < 0.05) increased osteoblast counts, reduced endosteal space
      fibrosis, reduced periosteal proliferation indices, and improved bone turnover
      (fluorochrome stains) in amifostine-treated animals. CONCLUSION: This study
      suggests that amifostine cytoprotection is mediated through a combination of
      reduced cellular injury with enhanced promotion of cellular bone rebuilding
      potential.

PMID- 22456378
TI  - Amifostine remediates the degenerative effects of radiation on the mineralization
      capacity of the murine mandible.
AB  - BACKGROUND: Radiotherapy, a cornerstone of head and neck cancer treatment, causes
      substantial morbidity to normal adjoining bone. The authors assessed the
      radioprotective effect of amifostine therapy on the mineralization of the
      mandible using micro-computed tomography. They hypothesized that amifostine would
      safeguard the mandible from radiation-induced disruption of the mineralization
      process and the associated failure of new bone creation. METHODS: Male Sprague
      Dawley rats were randomized into three groups: control (n = 8), radiation therapy
      (n = 5), and amifostine (n = 8). Animals in the radiation therapy and amifostine
      groups underwent human bioequivalent radiation of 70 Gy in five fractions to the
      left hemimandible. Fifty-six days after irradiation, the hemimandibles were
      harvested for radiomorphometric analyses. RESULTS: Amifostine-treated animals
      exhibited less alopecia, mucositis, and weight loss in addition to increased
      cortical density in comparison with those treated with radiation therapy. Bone
      and tissue mineral densities showed statistically significant improvement in
      amifostine versus radiation therapy, and no difference was observed between
      amifostine and control groups. Detailed micro-computed tomographic analysis
      further demonstrated significant differences in the mineralization profile when
      comparing radiation therapy and amifostine. Amifostine maintained regions of
      lower mineralization consistent with the preservation of normal remodeling.
      CONCLUSIONS: The authors have successfully demonstrated the ability of amifostine
      pretreatment to protect the natural mineralization profile of bone. This reflects
      the capacity of amifostine prophylaxis to safeguard the normal surrounding
      mandible from the impediments of collateral damage imposed by irradiation.
      Further study can correlate these findings with the potential use of amifostine
      to prevent the devastating associated morbidities of radiotherapy such as
      pathologic fractures and osteoradionecrosis.

PMID- 22456379
TI  - Clinical outcomes following supraorbital foraminotomy for treatment of frontal
      migraine headache.
AB  - BACKGROUND: Although 92 percent of patients who undergo surgical decompression of
      the supraorbital nerve for treatment of frontal migraine headaches through
      resection of the glabellar muscle group achieve at least 50 percent improvement,
      only two-thirds demonstrate complete resolution of symptoms. The authors
      investigated the role of additional decompression methods by comparing surgery
      outcomes between patients who underwent glabellar myectomy alone and patients who
      also underwent supraorbital foraminotomy. METHODS: Outcome measures including
      migraine headache frequency, severity, and duration; Migraine Headache Index
      score; and forehead pain were reviewed retrospectively and analyzed statistically
      for 43 age-matched control patients who underwent glabellar myectomy for release
      of the supraorbital nerve and 43 patients who underwent glabellar myectomy with
      supraorbital foraminotomy from 2002 to 2010. RESULTS: The myectomy group
      statistically matched the myectomy with foraminotomy group for age, number of
      surgical sites, and preoperative headache characteristics (p > 0.05). For the
      myectomy and myectomy with foraminotomy groups, postoperative migraine frequency
      was 7.8 per month versus 4.1 per month, severity was 5.6 versus 4.4, Migraine
      Headache Index score was 26.5 versus 11.1, and persistent forehead pain was 48.8
      percent versus 25.6 percent, respectively. These differences were all
      statistically significant (p < 0.05). Duration of headache was unchanged (p =
      0.17). CONCLUSIONS: The supraorbital foramen is a potential site of supraorbital
      nerve compression that can trigger frontal migraine headache. If it is present,
      the authors strongly recommend foraminotomy to ensure complete release of the
      supraorbital nerve to optimize outcomes. Their results also support consideration
      of release of any fibrous bands across the supraorbital notch. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 22456380
TI  - An individualized approach to severe elbow burn contractures.
AB  - Contracture of the antecubital fossa is a common occurrence following thermal
      burn injury to the upper extremity. Scarring of the superficial tissues can be
      treated with a variety of surgical methods to provide release and coverage.
      However, complex scarring of the elbow, which involves the deeper structures,
      requires a patient-specific technique for which each scarred, shortened, or
      contracted component is purposefully addressed during the operation. In addition,
      severe elbow contractures may be complicated by other conditions, such as
      peripheral neuropathy and heterotopic ossification. This article will discuss the
      evaluation of the patient with a severe elbow burn contracture and emphasize the
      importance of an individualized and comprehensive surgical approach. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 22456381
TI  - Perioperative morbidity in posterior cranial vault expansion: distraction
      osteogenesis versus conventional osteotomy.
AB  - BACKGROUND: The treatment of multisuture syndromic craniosynostosis is in
      evolution, with an increasing prevalence of reports on posterior vault expansion
      with distraction osteogenesis over conventional osteotomy. The purported benefits
      of distraction osteogenesis include less perioperative morbidity. The authors
      conducted this preliminary study to compare the perioperative course in children
      undergoing posterior cranial vault expansion with distraction osteogenesis versus
      conventional osteotomy. METHODS: A query was performed of the authors'
      institutional review board-approved, prospective, craniofacial registry for
      posterior cranial expansion between 2008 and 2011. Data collected included age,
      weight, diagnosis, surgical procedure and duration, perioperative laboratory
      data, number of perioperative blood donor exposures, length of intensive care
      unit and hospital stay, and intraoperative and postoperative complications. Data
      for conventional osteotomy and distraction osteogenesis were then compared.
      RESULTS: The registry query returned data from 25 subjects (16 with conventional
      osteotomy and nine with distraction osteogenesis). There were no significant
      differences in age or weight between the two groups. Mean total surgery time for
      conventional osteotomy was 239 +/- 48 minutes versus 200 +/- 70 minutes for
      distraction osteogenesis (p = 0.11). Intensive care unit stay was a median of 3.5
      days with conventional osteotomy versus 4.0 days for distraction osteogenesis (p
      = 0.10). There was no statistically significant difference in median hospital
      length of stay, calculated blood loss in blood volumes, total perioperative blood
      donor exposures, intraoperative complications, or postoperative complications.
      CONCLUSIONS: The results from this review of the authors' early experience with
      posterior vault distraction osteogenesis suggest that distraction osteogenesis
      and conventional osteotomy have similar perioperative safety and morbidity
      profiles. These data may seem counterintuitive, and the perioperative course of
      children undergoing distraction osteogenesis is likely to improve as experience
      with distraction osteogenesis increases. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 22456382
TI  - A multicenter, prospective, randomized, single-blind, controlled clinical trial
      comparing VASER-assisted Lipoplasty and suction-assisted Lipoplasty.
AB  - BACKGROUND: No scientific comparative study has demonstrated any statistically
      significant clinical improvement attributable to a new lipoplasty technology
      relative to traditional suction-assisted lipoplasty. This prospective study used
      a contralateral study design to evaluate postoperative differences between
      vibration amplification of sound energy at resonance (VASER)-assisted lipoplasty
      and suction-assisted lipoplasty. METHODS: Twenty female patients between the ages
      of 20 and 48 years received contralateral treatment with suction-assisted
      lipoplasty and VASER-assisted lipoplasty in one or more anatomical regions for a
      total of 33 regions. Patients received suction-assisted lipoplasty on one side of
      the body and VASER-assisted lipoplasty on the contralateral side. Patients were
      blinded to technology application. Aspirate was analyzed for blood content, and
      skin retraction was analyzed by measuring changes in ultraviolet light tattoos.
      RESULTS: Regarding skin retraction, the VASER-assisted lipoplasty-treated side
      resulted in a statistically significant improvement in skin retraction of 53
      percent relative to suction-assisted lipoplasty (17 percent per liter versus 11
      percent per liter, p = 0.003) with 33 paired sites using a two-tailed t test.
      Regarding blood loss, VASER-assisted lipoplasty treatment resulted in a
      statistically significant reduction in blood loss of 26 percent (11.2 versus 14.0
      cc blood/100 cc) relative to the suction-assisted lipoplasty side (p = 0.019 with
      n = 20 using a two-tailed t test). Subjective measures (i.e., pain, swelling,
      appearance, and patient and physician preference) showed no statistical
      difference between the two methods at the 6-month evaluation. CONCLUSIONS: The
      VASER-assisted lipoplasty method demonstrated improved skin retraction and
      reduction in blood loss compared with suction-assisted lipoplasty. This is the
      first study to demonstrate statistically significant and clinically relevant
      improvements in a new lipoplasty technology relative to suction-assisted
      lipoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

PMID- 22456383
TI  - Discussion: a multicenter, prospective, randomized, single-blind, controlled
      clinical trial comparing VASER-assisted lipoplasty and suction-assisted
      lipoplasty.

PMID- 22456384
TI  - Lysis of the orbicularis retaining ligament and orbicularis oculi insertion:  a
      powerful modality for lower eyelid and cheek rejuvenation.
AB  - BACKGROUND: The techniques of lower blepharoplasty are evolving to reflect the
      concept that the lower eyelid contour does not stop at the inferior orbital rim,
      and that the lid-cheek junction must often be modified to restore the midface to
      a youthful configuration. Multiple procedures have been proposed to smooth the
      lid-cheek junction and tear trough. The author proposes a technique of carbon
      dioxide laser lysis of the orbicularis retaining ligament and of the orbicularis
      oculi insertion onto the maxilla to release the tethering of the lower lid and
      cheek and allow recontouring of the lid-cheek junction in an extended
      transcutaneous lower blepharoplasty. METHODS: Retrospective review of 80 extended
      lower blepharoplasty procedures with carbon dioxide laser lysis of the
      orbicularis retaining ligament and of the orbicularis oculi insertion performed
      in the past 3 years was undertaken. Follow-up ranged from 4 to 26 months, with an
      average of 7.2 months. The efficacy, risks, and complications of this procedure
      were assessed. RESULTS: The complication rate for this procedure is not
      significantly higher than that for standard transcutaneous blepharoplasty, and
      the procedure allows significant improvement of the lid-cheek junction and
      rejuvenation of the upper midface. CONCLUSIONS: Lysis of the orbicularis
      retaining ligament and lower orbicularis oculi insertion is a safe and effective
      adjunct to lower blepharoplasty. It is a powerful modality that allows
      significant rejuvenation of the lid-cheek complex and upper cheek. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 22456385
TI  - Ear deformities, otoplasty, and ear reconstruction.
AB  - LEARNING OBJECTIVES: After reviewing this article, the participant should be able
      to: 1. Evaluate patient's ears for needed adjustments to size, shape, prominence,
      and symmetry. 2. Identify common ear deformities and describe methods to repair
      them. 3. Avoid or manage common complications associated with otoplasty and ear
      reconstruction. SUMMARY: The essentials of otoplasty will be
      described/illustrated for the following conditions: Prominent ears,
      underdeveloped helical rims (shell ear), macrotia, Stahl's ear, constricted ear,
      cryptotia, and question mark ear.

PMID- 22456386
TI  - Beyond working hours: part II. incentive to improve.
AB  - Efforts to limit resident work hours are conceptually flawed. A fundamental
      solution to resident service requires funding, which currently is not feasible.
      An equally fundamental structuring of the system of surgical resident education
      is feasible and should be attained.

PMID- 22456387
TI  - Deep and superficial eyelid fascia.

PMID- 22456389
TI  - Nasal reconstruction with free tissue transfer assisted by "delay".

PMID- 22456390
TI  - Pharmacologic therapies for infantile hemangioma:  is there a rational basis?

PMID- 22456392
TI  - TallyHo diabetic phenotype limited to male mice: female mice provide obese,
      nondiabetic mouse model.

PMID- 22456395
TI  - External or internal jugular vein? Recipient vein selection in head and neck free
      tissue transfer:  an evidence-based systematic analysis.

PMID- 22456396
TI  - Incidence of postoperative obstruction at different sites of lacrimal canalicular
      injury.

PMID- 22456397
TI  - Comparison of efficacy of intralesional bleomycin and oral propanolol in
      management of hemangiomas.

PMID- 22456398
TI  - Objective quantification of wrinkles:  three-dimensional analysis of surface
      irregularity.

PMID- 22456399
TI  - Establishing the safety and efficacy of simultaneous face lift and intraoperative
      full face and neck fractional carbon dioxide resurfacing.

PMID- 22456400
TI  - A new method for evaluating the outcome of rhinoplasty on the nasal tip.

PMID- 22456401
TI  - A modified application of pyriform ligament release for nasal base reduction.

PMID- 22456402
TI  - Stereolithographic modeling in reconstructive surgery of the craniofacial
      skeleton after tumor resection.

PMID- 22456403
TI  - Introduction of an individualized palatal splint for wound protection after cleft
      palate repair.

PMID- 22456404
TI  - A technique to improve the geometric and unnatural appearance of the inferior
      triangular flap in primary unilateral cleft lip repair.

PMID- 22456405
TI  - Treatment of mandibular angle fractures using the modified Risdon approach.

PMID- 22456406
TI  - Mandibular volumetric comparison of treacher collins syndrome and hemifacial
      microsomia.

PMID- 22456407
TI  - An analysis of mandibular volume in treacher collins syndrome.

PMID- 22456408
TI  - Desmoid tumor (fibromatosis) of the breast after augmentation with saline
      implants.

PMID- 22456409
TI  - Breastfeeding from mammary glands covered at the beginning of breast development
      by an expanded abdominal flap.

PMID- 22456410
TI  - A method of preoperatively assessing the volume of abdominal tissue available for
      an autologous breast reconstruction.

PMID- 22456411
TI  - Clockwise pattern pathologic examination in breast reduction mammaplasty.

PMID- 22456412
TI  - How to improve shape and projection in mastopexy.

PMID- 22456413
TI  - Use of a headless compressive screw (acutrak) for radioulnar joint fusion in the
      Sauve-Kapandji procedure.

PMID- 22456414
TI  - Modified camitz opponensplasty using transverse carpal ligament loop pulley in
      patients with advanced carpal tunnel syndrome.

PMID- 22456415
TI  - Self-wrist cutting injury:  a traumatologic and psychological analysis.

PMID- 22456416
TI  - Liposuction:  an exceptional case of skin necrosis secondary to an error of
      infiltration.

PMID- 22456417
TI  - Free-flap salvage by thrombolytic agents? An evidence-based systemic analysis.

PMID- 22456418
TI  - Overview of treatments for male genital lymphedema:  critical literature review
      and anatomical considerations.

PMID- 22456419
TI  - Evaluation of diagnostic accuracy using preoperative handheld Doppler in
      identifying the cutaneous perforators in the anterolateral thigh flap:  a
      systematic review.

PMID- 22456420
TI  - Efficacy study of hyaluronidase as a diffusion promoter for lidocaine in
      infiltration analgesia of skin.

PMID- 22456421
TI  - Intradermal injection of normal saline prevents cutaneous complications
      associated with sclerotherapy for superficial venous malformations.

PMID- 22456422
TI  - Paging plastics:  the issues confronting the most consulted service.

PMID- 22456423
TI  - Activation and amplification of the third-order NLO and luminescent responses of
      a precursor cluster by a supramolecular approach.
AB  - Solvothermal reactions of [Et(4)N][Tp*WS(3)(CuCl)(3)] (1) (Tp* = hydridotris(3,5
      dimethylpyrazol-1-yl)borate) with CuCN and KCu(CN)(2) afforded two
      [Tp*WS(3)Cu(3)]-based coordination polymers [Tp*WS(3)Cu(3)(MU(3)
      DMF){Cu(CN)(3)}](2) (2) and K[Tp*WS(3)Cu(3)(MU(3)-DMF){Cu(2)(CN)(4.5)}](2) (3).
      The third-order NLO and PL responses of 1 were activated and greatly amplified
      through its assembly via the [Cu(CN)(3)](2-) and [Cu(4)(CN)(9)](5-) species in 2
      and 3.

PMID- 22456424
TI  - Investigation of signal fading in lithium formate EPR dosimeters using a new
      sensitive method.
AB  - The aim of this study was to investigate signal fading in lithium formate
      electron paramagnetic resonance (EPR) dosimeters used for clinical applications
      in radiotherapy. A new experimental method for determination of signal fading,
      designed to resolve small changes in signal from slowly decaying unstable
      radicals, was used. Possible signal fading in lithium formate due to different
      storage temperatures was also tested. Air humidity was kept at a constant level
      of 33% throughout the experiments. The conclusion drawn from the investigations
      was that the EPR signal from lithium formate is stable during at least 1 month
      after irradiation and is not sensitive to variations in storage temperature <40 
      degrees C when kept at a relative air humidity of 33%. This makes lithium formate
      a suitable dosimeter for transfer dosimetry in clinical audits.

PMID- 22456425
TI  - Combination chemoprevention:  future direction of colorectal cancer prevention.
AB  - Recent research has drawn attention to protective effects of chemopreventive
      agents that reverse, suppress, or prevent the carcinogenic progression using
      pharmacological or nutritional agents. Aspirin and celecoxib are the promising
      preventive agents to effectively reduce the risk of colorectal cancer, but such
      agents are associated with severe gastrointestinal and cardiovascular side
      effects in long-term administration at high doses. Recently, the strategy that
      combinational use with several chemopreventive agents at low doses induces
      greater inhibition of carcinogenesis has become the focus. The nonsteroidal anti
      inflammatory drugs (NSAIDs) may combine with ornithine decarboxylase inhibitors,
      hydroxymethylglutaryl-CoA reductase inhibitors, epidermal growth factor signaling
      inhibitors, peroxisome proliferator-activated receptor-gamma ligands, and tumor
      necrosis factor-related apoptosis-inducing ligand, to magnify the
      chemoprophylactic effect. It is noteworthy that the phase III trial of
      difluoromethylornithine combination with sulidac has shown greater and effective
      preventive roles, which pave the way for the use of combinations of other agents.
      The long-term statins and low-dose NSAIDs have also been associated with risk
      reduction in vitro, in vivo, and in retrospective studies; however, the data are
      inconsistent. Epidermal growth factor signaling inhibitors, peroxisome
      proliferator-activated receptor-gamma ligands and tumor necrosis factor-related
      apoptosis-inducing ligand have been demonstrated to potentiate the preventive
      effects of NSAIDs in vitro and in vivo, but these combinational regimens have not
      yet been applied to clinical research. The major goal of this study was to review
      combination chemoprevention for colorectal cancer by means of combining low doses
      of potential preventive agents to increase their chemoprophylaxis efficacy and to
      minimize toxicity.

PMID- 22456426
TI  - Risk of lymphoma in women with breast implants:  analysis of clinical studies.
AB  - Large studies suggest that the overall rate of lymphoma in women with breast
      implants is no greater than in the general population; clinical reports suggest
      an association between breast implants and the rare non-Hodgkin lymphoma,
      anaplastic large cell lymphoma (ALCL). Observed cases of lymphoma reported in
      Allergan-sponsored breast implant clinical studies were compared with expected
      cases on the basis of the incidence of lymphoma among women in the National
      Cancer Institute's Surveillance Epidemiology and End Results program, using
      standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). In
      clinical studies, there were 28 observed cases of lymphoma among 89 382 patients
      and 204 682 person-years of follow-up compared with 43 expected cases [SIR:
      28/43=0.65 (95% CI: 0.43-0.94), P=0.02]. SIRs were calculated stratifying by
      baseline cancer history: women without prior cancer [SIR: 17/24=0.70 (95% CI:
      0.41-1.13), P=0.17] and women with prior cancer [SIR: 11/14=0.79 (95% CI: 0.39
      1.41), P=0.52]. SIRs were calculated by implant shell type: textured shell
      implants [SIR: 16/23=0.70 (95% CI: 0.40-1.13), P=0.16] and smooth shell implants
      [SIR: 12/19=0.63 (95% CI: 0.33-1.10), P=0.12]. Surveillance Epidemiology and End
      Results reported 12 cases of primary breast ALCL in women between 1996 and 2007
      without a history of cancer, for an average annual incidence of 4.28 (95% CI:
      3.51-5.05)/100 million women in the US - these women may or may not have breast
      implants. In clinical studies, three ALCL cases were reported in women with
      breast implants and a history of breast cancer, yielding a crude incidence rate
      of 1.46 (95% CI: 0.30-4.3)/100 000 person-years. Large clinical studies, based on
      over 200 000 person-years of follow-up, suggest no evidence of an increased risk
      of lymphoma among women who have received breast implants.

PMID- 22456427
TI  - An increased pulsatility index in transcranial Doppler sonography is associated
      with Shiga-toxin-related encephalopathy in hemolytic uremic syndrome.

PMID- 22456428
TI  - Maternal high-fat diet programs for metabolic disturbances in offspring despite
      leptin sensitivity.
AB  - A fatty diet during pregnancy in mouse dams causes metabolic abnormalities
      (similar to metabolic syndrome in humans) in the rodents' offspring. We tested
      the hypothesis that the offspring of dams fed a high-fat diet during pregnancy
      and lactation develop metabolic abnormalities and leptin resistance. Pregnant
      C57BL/6 mice (n = 20) were fed either standard chow (SC; 19% fat) or a high-fat
      diet (HF; 49% fat). After weaning, male offspring were divided into four groups,
      according to the diet of dams and offspring: SC(dams)/SC(offspring), SC/HF, HF/SC
      and HF/HF (n = 30/group). For a metabolic analysis, we evaluated body mass, fat
      mass depots, blood plasma and adipocyte structure at 12 weeks of age. To analyse
      leptin sensitivity, each group was divided into two groups (vehicle or leptin) to
      identify the feeding response and pSTAT3 expression after acute
      intracerebroventricular (ICV) treatment. The offspring of mothers fed a high-fat
      diet presented increased body mass and visceral fat, adipocyte hypertrophy and
      insulin resistance. This phenotype was not associated with central leptin
      resistance. Thus, maternal programming by HF predisposes offspring to metabolic
      abnormalities despite leptin sensitivity.

PMID- 22456429
TI  - Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2
      trial.
AB  - BACKGROUND: Brain metastases commonly develop in patients with melanoma and are a
      frequent cause of death of patients with this disease. Ipilimumab improves
      survival in patients with advanced melanoma. We aimed to investigate the safety
      and activity of this drug specifically in patients with brain metastases.
      METHODS: Between July 31, 2008, and June 3, 2009, we enrolled patients with
      melanoma and brain metastases from ten US centres who were older than 16 years
      into two parallel cohorts. Patients in cohort A were neurologically asymptomatic
      and were not receiving corticosteroid treatment at study entry; those in cohort B
      were symptomatic and on a stable dose of corticosteroids. Patients were to
      receive four doses of 10 mg/kg intravenous ipilimumab, one every 3 weeks.
      Individuals who were clinically stable at week 24 were eligible to receive 10
      mg/kg intravenous ipilimumab every 12 weeks. The primary endpoint was the
      proportion of patients with disease control, defined as complete response,
      partial response, or stable disease after 12 weeks, assessed with modified WHO
      criteria. Analyses of safety and efficacy included all treated patients. This
      trial is registered with ClinicalTrials.gov, number NCT00623766. FINDINGS: We
      enrolled 72 patients: 51 into cohort A and 21 into cohort B. After 12 weeks, nine
      patients in cohort A exhibited disease control (18%, 95% CI 8-31), as did one
      patient in cohort B (5%, 0.1-24). When the brain alone was assessed, 12 patients
      in cohort A (24%, 13-38) and two in cohort B (10%, 1-30) achieved disease
      control. We noted disease control outside of the brain in 14 patients (27%, 16
      42) in cohort A and in one individual (5%, 0.1-24) in cohort B. The most common
      grade 3 adverse events in cohort A were diarrhoea (six patients [12%]) and
      fatigue (six [12%]); in cohort B, they were dehydration (two individuals [10%]),
      hyperglycaemia (two [10%]), and increased concentrations of serum aspartate
      aminotransferase (two [10%]). One patient in each cohort had grade 4 confusion.
      The most common grade 3 immune-related adverse events were diarrhoea (six
      patients [12%]) and rash (one [2%]) in cohort A, and rash (one individual [5%])
      and increased concentrations of serum aspartate aminotransferase (two [10%]) in
      cohort B. One patient in cohort A died of drug-related complications of immune
      related colitis. INTERPRETATION: Ipilimumab has activity in some patients with
      advanced melanoma and brain metastases, particularly when metastases are small
      and asymptomatic. The drug has no unexpected toxic effects in this population.
      FUNDING: Bristol-Myers Squibb.

PMID- 22456430
TI  - Treatment of brain metastases in patients with melanoma.

PMID- 22456432
TI  - Expression of hMLH1, hMSH2 and hMSH6 in small intestinal carcinomas.
AB  - BACKGROUND/AIMS: Although primary small intestinal carcinoma (SIC) is
      morphologically similar to colorectal carcinoma and shares many of the genetic
      changes of carcinogenesis, little is known about the role of defective mismatch
      repair (MMR) genes involved in the SIC. The aim of this study is to investigate
      the role of defective MMR genes and correlation between clinicopathological
      factors and loss of MMR protein in SIC. METHODOLOGY: A total of 195 SIC cases
      were collected from 20 institutions in Korea and tissue microarrays (TMA) were
      made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by
      immunohistochemistry (IHC). RESULTS: The loss of expression of hMLH1, hMSH2 and
      hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%),
      respectively. The loss of hMSH2 expression was associated with retroperitoneal
      seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply
      and a higher frequency of pancreas invasion. The loss of hMSH6 expression was
      associated less frequently with peritumoral adenoma. There was no survival
      difference by MMR protein expression status. CONCLUSIONS: The loss of MMR protein
      was associated with some distinct clinicopathological features. MMR pathway seems
      to be major pathway in carcinogenesis of SICs. MMR defect seems to be related
      with sporadic-microsatellite instability (MSI).

PMID- 22456433
TI  - Surgical outcomes of minor hepatectomy for locally advanced gallbladder
      carcinoma.
AB  - BACKGROUND/AIMS: This study aimed to evaluate whether wedge resection or S4bS5
      resection was the more beneficial hepatectomy procedure for patients with locally
      advanced gallbladder carcinoma. METHODOLOGY: A retrospective analysis of 70
      patients who underwent either wedge resection (n=58) or S4bS5 resection (n=12)
      for locally advanced gallbladder carcinoma without clinically evident liver
      metastases was conducted. Clinicopathological characteristics, histological
      features of hepatic invasion and surgical outcomes were analyzed. RESULTS:
      Sixteen patients had tumors with hepatic invasion. Of the 16 patients with
      hepatic invasion, 6 had direct liver invasion alone and 10 had portal tract
      invasion featuring intrahepatic stromal invasion (n=5), intrahepatic lymphatic
      invasion (n=4) and intrahepatic venous invasion (n=l). The hepatectomy procedure
      was not significantly associated with survival after resection (p=0.518) as
      patients who underwent wedge resection showed an overall cumulative 3-year
      survival rate of 74% compared with 60% for patients who underwent S4bS5
      resection. The Cox proportional hazard regression analysis revealed that pT
      classification (p<0.001), pM classification (p=0.001) and resection of the
      extrahepatic bile duct (p=0.048) were independently significant factors
      associated with survival after resection. CONCLUSIONS: Hepatectomy procedure may
      not significantly affect surgical outcomes in patients with gallbladder
      carcinoma. Partial hepatectomy involving the gallbladder bed is critical due to
      possible tumor cells.

PMID- 22456434
TI  - Study on the DNA repair gene XRCC1 and XRCC3 polymorphism in prediction and
      prognosis of hepatocellular carcinoma risk.
AB  - BACKGROUND/AIMS: We conducted a case-control study in China to clarify the
      association between XRCC1-Arg-399Gin polymorphism and HCC risk. METHODOLOGY: A
      total of 150 cases and 158 controls were selected from May 2008 to May 2010.
      XRCC1-Arg399Gin and XRCC3-Thr241Met polymorphisms were based upon duplex
      polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method.
      All analysis was performed by using the STATA statistical package. RESULTS: A
      significant increased risk of HCC was associated with XRCC1 399Arg/Gin, and a
      heavy risk of HCC was also found in individuals with XRCC3 241Met/Met genotypes.
      A significant association was found between positive HBsAg and Arg/Gin. XRCC3
      Thr/Met genotypes had a significant positive association with HBsAg (+) and a
      heavy risk of HCC was found in HBsAg (+) individuals with XRCC3 Met/Met genotype.
      Individuals carrying XRCC1 Gin/Gin genotypes showed significantly lower median
      survival than XRCC1 Arg/ Arg genotypes and significant hazard ratio (HR=l.38, 95%
      CI=l.04-1.84) was found. Meanwhile, we found a moderate HR for XRCC3 Thr/Met
      (HR=l.96, 95% CI=l.23-3.15) and a heavy HR for XRCC3 Met/Met (HR=2.98, 95%
      CI=1.77-7.54). CONCLUSIONS: In conclusion, we observed that XRCC1-Arg399Gln and
      XRCC3-Thr241Met polymorphism is associated with susceptibility to HCC and XRCC1
      Gin allele and XRCC3 Met allele genotype showed significant poor prognosis of
      HCC.

PMID- 22456436
TI  - 3' self-inactivating long terminal repeat inserts for the modulation of transgene
      expression from lentiviral vectors.
AB  - Gene transfer for research or gene therapy requires the design of vectors that
      allow for adequate and safe transgene expression. Current methods to modulate the
      safety and expression profile of retroviral vectors can involve the insertion of
      insulators or scaffold/matrix-attachment regions in self-inactivating long
      terminal repeats (SIN-LTRs). Here, we generated a set of lentiviral vectors (with
      internal CMV or PGK promoter) in which we inserted (at the level of SIN-LTRs)
      sequences of avian (i.e., chicken hypersensitive site-4, cHS4), human (i.e.,
      putative insulator and desert sequence), or bacterial origin. We characterized
      them with respect to viral titer, integration, transduction efficiency and
      transgene expression levels, in both integrase-proficient and -deficient
      contexts. We found that the cHS4 insulator enhanced transgene expression by a
      factor of 1.5 only when cloned in the antisense orientation. On the other hand,
      cHS4 in the sense orientation as well as all other inserts decreased transgene
      expression. This attenuation phenomenon persisted over long periods of time and
      did not correspond to extinction or variegation. Decreased transgene expression
      was associated with lower mRNA levels, yet RNA stability was not affected.
      Insertions within the SIN-LTRs may negatively affect transgene transcription in a
      direct fashion through topological rearrangements. The lentiviral vectors that we
      generated constitute valuable genetic tools for manipulating the level of
      transgene expression. Moreover, this study demonstrates that SIN-LTR inserts can
      decrease transgene expression, a phenomenon that might be overcome by modifying
      insert orientation, thereby highlighting the importance of careful vector design
      for gene therapy.

PMID- 22456437
TI  - Osteoporosis-pseudoglioma syndrome: three novel mutations in the LRP5 gene and
      response to bisphosphonate treatment.
AB  - BACKGROUND/AIMS: Osteoporosis-pseudoglioma (OPPG) syndrome is a rare disorder
      characterized by congenital or infancy-onset visual loss and severe juvenile
      osteoporosis. OPPG is caused by homozygous mutations in the low-density
      lipoprotein receptor-related protein 5 (LRP5) gene. We present three novel
      homozygous LRP5 mutations found in 3 unrelated Turkish children with
      consanguineous parents, along with clinical phenotypes and response to treatment
      with bisphosphonates (bisP). METHODS/RESULTS: The LRP5 gene was analyzed by
      direct sequencing after PCR amplification. Mutation screening for LRP5 revealed
      homozygous nonsense R1002X mutation in the first patient and homozygous missense
      mutations V336M and G507S in the second and third patient, respectively. The
      parents were heterozygous for these mutations. The patients' eye symptoms began
      during the first months of life but the OPPG diagnoses were made based on
      skeletal deformities and osteopenia after 4 years of age. The patients' bone
      mineral density Z scores were very low and consistent with osteopenia. All
      patients were treated with bisP for 3.5-7 years. CONCLUSION: We report three
      novel LRP5 mutations in 3 Turkish patients with OPPG. We show that the response
      of bisP therapy has improved the lumbar spinal bone mineral density Z scores and
      the patients' quality of life as the bone pains decreased.

PMID- 22456438
TI  - Fetal-type erythropoiesis is more closely linked to glycated minor hemoglobin
      fractions than hemoglobin A(1c) in diabetics.

PMID- 22456439
TI  - Reversal of severe methotrexate-induced intestinal damage using enteral n-3 fatty
      acids.
AB  - Growing evidence suggests that n-3 PUFA and their specific lipid mediators can
      reduce the activity of inflammatory processes. In the present study, we evaluated
      the effects of oral n-3 PUFA supplementation on intestinal structural changes,
      enterocyte proliferation and apoptosis during methotrexate (MTX)-induced
      intestinal damage in the rat. A total of thirty-two male rats were divided into
      four experimental groups: control (CONTR) rats; CONTR-n-3 PUFA rats treated with
      oral administration of n-3 PUFA at a dose of 300 MUg/kg once per d 72 h before
      and 72 h following vehicle injection; MTX rats treated with a single dose of MTX;
      MTX-n-3 PUFA rats treated with oral n-3 PUFA following the injection of MTX.
      Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation
      and enterocyte apoptosis determined 72 h following MTX injection. Real-time PCR
      was used to determine B-cell lymphoma 2 (Bcl2)-associated X protein (Bax) and
      Bcl2 mRNA expression. Western blotting was used to determine phosphorylated
      extracellular signal-related kinase, beta-catenin, Bax and Bcl2 protein levels.
      MTX-n-3 PUFA rats demonstrated a greater jejunal and ileal bowel weight, greater
      ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater
      villus height in the jejunum and ileum and crypt depth in the ileum, compared
      with MTX animals. A significant decrease in enterocyte apoptosis in the ileum of
      MTX-n-3 PUFA rats (v. MTX) was accompanied by decreased Bax mRNA and protein
      expression and increased Bcl2 mRNA levels. Thus, the treatment with oral n-3 PUFA
      prevented mucosal injury and improved intestinal recovery following MTX-injury in
      rats.

PMID- 22456440
TI  - Ion clustering in electrospray mass spectrometry of brine and other electrolyte
      solutions.
AB  - Electrospray ionization is suggested as a complementary technique for the
      investigation of the solution chemistry of metal salts, which allows us to
      achieve direct insight into the molecular entities present in solution. While the
      transfer of the metal ions from solution to the gas phase in the course of the
      electrospray process is associated with significant changes in concentration, pH,
      and also composition in the case of mixed solvents, systematic studies of
      concentration series can provide criteria to assess the extent to which the gas
      phase data correlate with the situation in solution. While there does not exist a
      1 ? 1 correlation between mass spectrometric measurements and solution
      properties, very useful qualitative molecular insights can be achieved and
      quantitative analysis can be made once the specific circumstances of the
      ionization process are taken into account.

PMID- 22456441
TI  - Adaptation: Malarial bet hedging.

PMID- 22456442
TI  - DNA tetraplex structure formation from human telomeric repeat motif
      (TTAGGG):(CCCTAA) in nanocavity water pools of reverse micelles.
AB  - In an equimolar ratio the human telomeric oligonucleotides d[AGGG(TTAGGG)(3)] and
      d[(CCCTAA)(3)CCCT] formed mixed structures of duplex and tetraplex in bis(2
      ethylhexyl)sulfosuccinate reverse micelles; only the duplex was observed in
      aqueous buffer. This finding suggests that heterogeneous confined media in the
      cell nucleus might induce a significant fraction of the telomeric region of
      genomic DNA to adopt non-canonical tetraplex structure.

PMID- 22456443
TI  - Sensation seeking and impulsivity: combined associations with risky sexual
      behavior in a large sample of young adults.
AB  - Although prior studies have shown that sensation seeking and impulsive decision
      making are related to sexual risk-taking, it is still unclear whether these
      personality traits operate independently or synergistically. The purpose of this
      study was to elucidate the joint contribution of these personality traits to HIV
      and sexually transmitted disease (STD) risk behaviors using data from a large
      sample of sexually active young adults (N = 2,386). Regression modeling indicated
      that both sensation seeking and impulsive decision-making were consistently
      associated with sexual risk behaviors across 11 risk-related outcomes. Results
      further indicated that sensation seeking and impulsive decision-making operated
      synergistically with respect to the outcome variables of sex acts using drugs,
      acts with a partner using alcohol, and acts with a partner using drugs. In
      contrast to this, sensation seeking and impulsive decision-making operated
      independently with respect to the other sexual risk outcomes. Theoretical
      implications, as well as implications for HIV/STD prevention among high sensation
      seekers and impulsive decision-makers, are discussed.

PMID- 22456444
TI  - Spatial and temporal dynamics of the microbial community in the Hanford
      unconfined aquifer.
AB  - Pyrosequencing analysis of 16S rRNA genes was used to study temporal dynamics of
      groundwater bacteria and archaea over 10 months within three well clusters
      separated by ~30 m and located 250 m from the Columbia River on the Hanford Site,
      WA. Each cluster contained three wells screened at different depths ranging from
      10 to 17 m that differed in hydraulic conductivities. Representative samples were
      selected for analyses of prokaryotic 16S and eukaryotic 18S rRNA gene copy
      numbers. Temporal changes in community composition occurred in all nine wells
      over the 10-month sampling period. However, there were particularly strong
      effects near the top of the water table when the seasonal rise in the Columbia
      River caused river water intrusion at the top of the aquifer. The occurrence and
      disappearance of some microbial assemblages (such as Actinobacteria ACK-M1) were
      correlated with river water intrusion. This seasonal impact on microbial
      community structure was greater in the shallow saturated zone than deeper zone in
      the aquifer. Spatial and temporal patterns for several 16S rRNA gene operational
      taxonomic units associated with particular physiological functions (for example,
      methane oxidizers and metal reducers) suggests dynamic changes in fluxes of
      electron donors and acceptors over an annual cycle. In addition, temporal
      dynamics in eukaryotic 18S rRNA gene copies and the dominance of protozoa in 18S
      clone libraries suggest that bacterial community dynamics could be affected not
      only by the physical and chemical environment but also by top-down biological
      control.

PMID- 22456445
TI  - Stochastic and deterministic assembly processes in subsurface microbial
      communities.
AB  - A major goal of microbial community ecology is to understand the forces that
      structure community composition. Deterministic selection by specific
      environmental factors is sometimes important, but in other cases stochastic or
      ecologically neutral processes dominate. Lacking is a unified conceptual
      framework aiming to understand why deterministic processes dominate in some
      contexts but not others. Here we work toward such a framework. By testing
      predictions derived from general ecological theory we aim to uncover factors that
      govern the relative influences of deterministic and stochastic processes. We
      couple spatiotemporal data on subsurface microbial communities and environmental
      parameters with metrics and null models of within and between community
      phylogenetic composition. Testing for phylogenetic signal in organismal niches
      showed that more closely related taxa have more similar habitat associations.
      Community phylogenetic analyses further showed that ecologically similar taxa
      coexist to a greater degree than expected by chance. Environmental filtering thus
      deterministically governs subsurface microbial community composition. More
      importantly, the influence of deterministic environmental filtering relative to
      stochastic factors was maximized at both ends of an environmental variation
      gradient. A stronger role of stochastic factors was, however, supported through
      analyses of phylogenetic temporal turnover. Although phylogenetic turnover was on
      average faster than expected, most pairwise comparisons were not themselves
      significantly non-random. The relative influence of deterministic environmental
      filtering over community dynamics was elevated, however, in the most temporally
      and spatially variable environments. Our results point to general rules governing
      the relative influences of stochastic and deterministic processes across micro-
      and macro-organisms.

PMID- 22456446
TI  - Viral clones from the GOS expedition with an unusual photosystem-I gene cassette
      organization.
AB  - Cyanobacteria have a key role in marine photosynthesis, which contributes to the
      global carbon cycle and to the world oxygen supply. Genes encoding for
      photosystem-II (PSII) and photosystem-I (PSI) reaction centers are found in
      different cyanophage genomes, and it was suggested that the horizontal transfer
      of these genes might be involved in increasing phage fitness. We have further
      analyzed a rare viral Global Ocean Sampling (GOS) clone containing PSI genes.
      This clone contains the unusual PSI gene organization psaD->C->A, as opposed to
      the more frequently observed viral psaJF->C->A->B->K->E->D organization, and was
      detected only once in the GOS metagenome. Our analyses identified more
      occurrences with similar arrangement and indicate that this PSI viral gene
      organization (now psaD->C->A->B), although rare, is authentic and represents a
      new PSI gene arrangement.

PMID- 22456447
TI  - 'Candidatus Thermochlorobacter aerophilum:' an aerobic chlorophotoheterotrophic
      member of the phylum Chlorobi defined by metagenomics and metatranscriptomics.
AB  - An uncultured member of the phylum Chlorobi, provisionally named 'Candidatus
      Thermochlorobacter aerophilum', occurs in the microbial mats of alkaline
      siliceous hot springs at the Yellowstone National Park. 'Ca. T. aerophilum' was
      investigated through metagenomic and metatranscriptomic approaches. 'Ca. T.
      aerophilum' is a member of a novel, family-level lineage of Chlorobi, a
      chlorophototroph that synthesizes type-1 reaction centers and chlorosomes similar
      to cultivated relatives among the green sulfur bacteria, but is otherwise very
      different physiologically. 'Ca. T. aerophilum' is proposed to be an aerobic
      photoheterotroph that cannot oxidize sulfur compounds, cannot fix N(2), and does
      not fix CO(2) autotrophically. Metagenomic analyses suggest that 'Ca. T.
      aerophilum' depends on other mat organisms for fixed carbon and nitrogen, several
      amino acids, and other important nutrients. The failure to detect bchU suggests
      that 'Ca. T. aerophilum' synthesizes bacteriochlorophyll (BChl) d, and thus it
      occupies a different ecological niche than other chlorosome-containing
      chlorophototrophs in the mat. Transcription profiling throughout a diel cycle
      revealed distinctive gene expression patterns. Although 'Ca. T. aerophilum'
      probably photoassimilates organic carbon sources and synthesizes most of its cell
      materials during the day, it mainly transcribes genes for BChl synthesis during
      late afternoon and early morning, and it synthesizes and assembles its
      photosynthetic apparatus during the night.

PMID- 22456449
TI  - Turing patterns in the chlorine dioxide-iodine-malonic acid reaction with square
      spatial periodic forcing.
AB  - We use the photosensitive chlorine dioxide-iodine-malonic acid reaction-diffusion
      system to study wavenumber locking of Turing patterns to two-dimensional "square"
      spatial forcing, implemented as orthogonal sets of bright bands projected onto
      the reaction medium. Various resonant structures emerge in a broad range of
      forcing wavelengths and amplitudes, including square lattices and superlattices,
      one-dimensional stripe patterns and oblique rectangular patterns. Numerical
      simulations using a model that incorporates additive two-dimensional spatially
      periodic forcing reproduce well the experimental observations.

PMID- 22456448
TI  - Nodularin, a cyanobacterial toxin, is synthesized in planta by symbiotic Nostoc
      sp.
AB  - The nitrogen-fixing bacterium, Nostoc, is a commonly occurring cyanobacterium
      often found in symbiotic associations. We investigated the potential of cycad
      cyanobacterial endosymbionts to synthesize microcystin/nodularin. Endosymbiont
      DNA was screened for the aminotransferase domain of the toxin biosynthesis gene
      clusters. Five endosymbionts carrying the gene were screened for bioactivity.
      Extracts of two isolates inhibited protein phosphatase 2A and were further
      analyzed using electrospray ionization mass spectrometry (ESI-MS)/MS. Nostoc sp.
      'Macrozamia riedlei 65.1' and Nostoc sp. 'Macrozamia serpentina 73.1' both
      contained nodularin. High performance liquid chromatography (HPLC) HESI-MS/MS
      analysis confirmed the presence of nodularin at 9.55+/-2.4 ng MUg-1 chlorophyll a
      in Nostoc sp. 'Macrozamia riedlei 65.1' and 12.5+/-8.4 ng MUg-1 Chl a in Nostoc
      sp. 'Macrozamia serpentina 73.1' extracts. Further scans indicated the presence
      of the rare isoform [L-Har(2)] nodularin, which contains L-homoarginine instead
      of L-arginine. Nodularin was also present at 1.34+/-0.74 ng ml(-1) (approximately
      3 pmol per g plant ww) in the methanol root extracts of M. riedlei MZ65, while
      the presence of [L-Har(2)] nodularin in the roots of M. serpentina MZ73 was
      suggested by HPLC HESI-MS/MS analysis. The ndaA-B and ndaF genomic regions were
      sequenced to confirm the presence of the hybrid polyketide/non-ribosomal gene
      cluster. A seven amino-acid insertion into the NdaA-C1 domain of N. spumigena
      NSOR10 protein was observed in all endosymbiont-derived sequences, suggesting the
      transfer of the nda cluster from N. spumigena to terrestrial Nostoc species. This
      study demonstrates the synthesis of nodularin and [L-Har(2)] nodularin in a non
      Nodularia species and the production of cyanobacterial hepatotoxin by a symbiont
      in planta.

PMID- 22456450
TI  - Novel application of EEG source localization in the assessment of the penumbra.

PMID- 22456452
TI  - DFT investigation of NH3 physisorption on CuSO4 impregnated SiO2.
AB  - In this quantum chemical investigation, NH(3) physisorption onto a model of
      copper sulfate impregnated silica is compared with pure silica and copper sulfate
      adsorbents. The physisorption process is modeled as direct binding of the NH(3)
      molecule to the adsorption site of the dry adsorbents and as displacement of a
      H(2)O molecule by NH(3) in the hydrated complexes. The surface of silica is
      represented by a hydroxyl group attached to a silsesquioxane cage,
      H(7)Si(8)O(12)(OH) and silica impregnated with CuSO(4) by the most stable
      configuration of the cluster containing a CuSO(4) ion pair placed adjacent to the
      silica cage. H(2)O is systematically added to the dehydrated adsorbents to
      investigate the role of water in NH(3) adsorption. Modeling hydrated environments
      of each type of adsorbent is focused on H(2)O molecules that directly coordinate
      with the active sites. The results indicate that the binding energy of adsorbing
      NH(3) onto the mixed adsorbent is greater than in pure silica. This enhanced
      binding in the mixed adsorbent is consistent with improved Bronsted acidity of
      the silanol in the presence of CuSO(4).

PMID- 22456451
TI  - Tracking cognitive change over 24 weeks with longitudinal functional magnetic
      resonance imaging in Alzheimer's disease.
AB  - BACKGROUND: Previous studies have revealed that functional magnetic resonance
      imaging (fMRI) blood oxygen level-dependent (BOLD) signal in specific brain
      regions correlates with cross-sectional performance on standardized clinical
      trial measures in Alzheimer's disease (AD); however, the relationship between
      longitudinal change in fMRI-BOLD signal and neuropsychological performance
      remains unknown. OBJECTIVE: To identify changes in regional fMRI-BOLD activity
      that tracks change in neuropsychological performance in mild AD dementia over 6
      months. METHODS: Twenty-four subjects (mean age 71.6) with mild AD dementia (mean
      Mini Mental State Examination 21.7, Global Clinical Dementia Rating 1.0) on
      stable donepezil dosing participated in two task-related fMRI sessions consisting
      of a face-name paired associative encoding memory paradigm 24 weeks apart during
      a randomized placebo-controlled pharmaco-fMRI drug study. Regression analysis was
      used to identify regions where the change in fMRI activity for Novel > Repeated
      stimulus contrast was associated with the change scores on postscan memory tests
      and the Free and Cued Selective Reminding Test (FCSRT). RESULTS: Correlations
      between changes in postscan memory accuracy and changes in fMRI activity were
      observed in regions including the angular gyrus, parahippocampal gyrus, inferior
      frontal gyrus and cerebellum. Correlations between changes in FCSRT-free recall
      and changes in fMRI were observed in regions including the inferior parietal
      lobule, precuneus, hippocampus and parahippocampal gyrus. CONCLUSION: Changes in
      encoding-related fMRI activity in regions implicated in mnemonic networks
      correlated with changes in psychometric measures of episodic memory retrieval
      performed outside the scanner. These exploratory results support the potential of
      fMRI activity to track cognitive change and detect signals of short-term
      pharmacologic effect in early-phase AD studies.

PMID- 22456453
TI  - Barriers and opportunities of empowerment as applied in diabetes settings: a
      focus on health care professionals' experiences.
AB  - This exploratory study examines the opportunities and barriers health care
      professionals (HCPs) working with diabetes patients face when they try to
      implement the rhetoric of patient empowerment in practice. A small sample of
      diabetes HCPs (N=13), from National Health Service (NHS) hospital, walk-in and
      general practitioner (GP) clinics in South-East England, was interviewed through
      in-depth semi-structured interviews. Interviews were recorded, transcribed
      verbatim and analysed thematically. The analysis showed that empowerment was seen
      as beneficial for patients and HCPs. Time and resources could be moved from
      successfully empowered patients and focussed on more complex patients, this was
      termed 'selective empowerment'. The main barriers to empowerment were identified
      as a lack of resources, time and HCPs trained in empowerment techniques.
      Empowerment is a popular concept in theory, and presents HCPs with several
      opportunities but also important barriers in its practical, clinical
      implementation day-to-day.

PMID- 22456454
TI  - Utility of HbA1c for diagnosis of gestational diabetes mellitus.
AB  - OBJECTIVE: To evaluate the utility of HbA(1c) in combination with OGTT for
      diagnosis of GDM. MATERIALS AND METHODS: 607 pregnant women with their estimated
      gestational age between 24 and 28 weeks were evaluated for GDM using OGTT based
      on ADA criteria. HbA(1c) was also done at the same time. RESULTS: The mean
      HbA(1c) value in women with GDM was significantly higher than women without GDM
      (5.73 +/- 0.34% compared to 5.34 +/- 0.35%). The area under ROC curve of HbA(1c)
      to detect GDM was 0.805 and an HbA(1c) cutoff value of >=5.95% had sensitivity of
      28.6% and specificity of 97.2% in diagnosing GDM while an HbA(1c) cutoff value of
      >=5.45% had sensitivity of 85.7% and specificity of 61.1% in diagnosing GDM. For
      women with an HbA(1c) value between 5.45% and 5.95%, an OGTT should be performed
      to correctly identify women with GDM. Using this methodology 85.7% of the GDM
      cases would have been detected and only 2.8% of normal women would have been
      wrongly labeled as having GDM. Also, this methodology would have obviated an OGTT
      in 61.8% women in our study. CONCLUSION: HbA(1c) in combination with OGTT can
      obviate the need of OGTT in almost two-thirds of women with GDM.

PMID- 22456455
TI  - Identifying individual DNA species in a complex mixture by precisely measuring
      the spacing between nicking restriction enzymes with atomic force microscope.
AB  - We discuss a novel atomic force microscope-based method for identifying
      individual short DNA molecules (<5000 bp) within a complex mixture by measuring
      the intra-molecular spacing of a few sequence-specific topographical labels in
      each molecule. Using this method, we accurately determined the relative abundance
      of individual DNA species in a 15-species mixture, with fewer than 100 copies per
      species sampled. To assess the scalability of our approach, we conducted a
      computer simulation, with realistic parameters, of the hypothetical problem of
      detecting abundance changes in individual gene transcripts between two single
      cell human messenger RNA samples, each containing roughly 9000 species. We found
      that this approach can distinguish transcript species abundance changes
      accurately in most cases, including transcript isoforms which would be
      challenging to quantitate with traditional methods. Given its sensitivity and
      procedural simplicity, our approach could be used to identify transcript-derived
      complementary DNAs, where it would have substantial technical and practical
      advantages versus established techniques in situations where sample material is
      scarce.

PMID- 22456456
TI  - Brownian motion or Levy walk? Stepping towards an extended statistical mechanics
      for animal locomotion.
AB  - Animals moving under the influence of spatio-temporal scaling and long-term
      memory generate a kind of space-use pattern that has proved difficult to model
      within a coherent theoretical framework. An extended kind of statistical
      mechanics is needed, accounting for both the effects of spatial memory and scale
      free space use, and put into a context of ecological conditions. Simulations
      illustrating the distinction between scale-specific and scale-free locomotion are
      presented. The results show how observational scale (time lag between relocations
      of an individual) may critically influence the interpretation of the underlying
      process. In this respect, a novel protocol is proposed as a method to distinguish
      between some main movement classes. For example, the 'power law in disguise'
      paradox-from a composite Brownian motion consisting of a superposition of
      independent movement processes at different scales-may be resolved by shifting
      the focus from pattern analysis at one particular temporal resolution towards a
      more process-oriented approach involving several scales of observation. A more
      explicit consideration of system complexity within a statistical mechanical
      framework, supplementing the more traditional mechanistic modelling approach, is
      advocated.

PMID- 22456457
TI  - Improving care through effectiveness, efficiency, equity, patient centeredness,
      safety, and timeliness with a diabetes update.

PMID- 22456458
TI  - Resolving moral distress when caring for patients who smoke while using home
      oxygen therapy.
AB  - More than 1 million people in the United States use home oxygen therapy and its
      demand is growing. However, there are dangers associated with its use, such as
      burns and home fires, and smoking is the most common cause of these incidents. As
      a result, home healthcare nurses feel intense emotional distress when caring for
      patients who smoke while using home oxygen therapy. This distress arises from the
      nurse's competing sense of moral duties toward these patients. The purpose of
      this article is to describe this distress, then to propose a 3-step process of
      taking concrete actions to resolve the distress.

PMID- 22456459
TI  - A pilot study using electronic communication in home healthcare: implications on
      parental well-being and satisfaction caring for medically fragile children.
AB  - The aim of this study was to explore the impact of a nurse-established and nurse
      managed electronic communication in the form of e-mail on the self-reported well
      being and satisfaction of parent's caring for medically fragile and
      technologically dependent children. This study was conducted in a pediatric home
      care agency located in the southeastern region of the United States. Nineteen
      parents and caregivers participated in a 3-month intervention. A
      quasiexperimental pre- and posttest design was used. There were no significant
      differences in pre- and postintervention parental self-reported well-being (p <
      .227) or satisfaction (p < .528). Parental qualitative comments suggest positive
      outcomes related to well-being and satisfaction. Further investigation into the
      utility of e-mail communication with parents of medically fragile and
      technologically dependent children cared for at home is warranted.

PMID- 22456460
TI  - Online resources for culturally and linguistically appropriate services in home
      healthcare and hospice, part 2: resources for Asian patients.
AB  - Home care and hospice clinicians are increasingly working with patients for whom
      English is not their primary language. Provision of culturally respectful and
      acceptable patient-centered care includes both an awareness of cultural beliefs
      that influence the patient's health and also the ability to provide the patient
      with health information in the language with which he or she is most comfortable.
      This article identifies resources for understanding the cultural norms of Asian
      born patients and appropriate patient education materials in the many languages
      spoken by this population. The resources have been made available free on the Web
      by healthcare professionals and government agencies from around the world.

PMID- 22456462
TI  - Cognitive impairment and medication self-management errors in older adults
      discharged home from a community hospital.
AB  - The purpose of this article is to report the results of a pilot study of the
      relationship between cognitive impairment and medication self-management errors
      in older adults discharged home from a community hospital. It is hoped that these
      preliminary data will provide some new ideas for reducing errors in medication
      self-management posthospitalization.

PMID- 22456463
TI  - An empirical study of self-efficacy and social support in diabetes self
      management: implications for home healthcare nurses.
AB  - This pilot study was conducted to evaluate relationships among self-efficacy,
      social support, social problem solving, and diabetes self-management in people
      living with Type 2 diabetes mellitus. Self-efficacy, social support, and social
      problem solving were significantly correlated with diabetes self-management.
      These relationships indicate the importance of including interventions to promote
      self-efficacy, social support, and social problem solving in diabetes self
      management programs.

PMID- 22456464
TI  - In healthcare quality, improvement starts with passionate leadership.

PMID- 22456465
TI  - Adverse drug reactions in older patients during hospitalisation: are they
      predictable?
AB  - BACKGROUND: adverse drug reactions (ADRs) are a major cause of morbidity and
      healthcare utilisation in older people. The GerontoNet ADR risk score aims to
      identify older people at risk of ADRs during hospitalisation. We aimed to assess
      the clinical applicability of this score and identify other variables that
      predict ADRs in hospitalised older people. METHODS: we prospectively studied 513
      acutely ill patients aged >=65 years. The GerontoNet ADR risk score was
      calculated for all patients. ADRs were identified through patient and physician
      consultation together with analysis of case notes. Receiver operator
      characteristic (ROC) curves were constructed to test the ability of the
      GerontoNet risk score to predict ADRs. Multivariate logistic regression examined
      the influence of individual variables on the presence of ADRs. RESULTS: in
      hospital ADRs were identified in 135 patients (26%). The area under the ROC curve
      was 0.62 (95% CI: 0.57-0.68). Variables which increased ADR risk include (i)
      renal failure (OR: 1.81, 95% CI: 1.12-2.92), (ii) increasing number of
      medications (OR: 1.09, 95% CI: 1.02-1.17) (iii) inappropriate medications (OR:
      2.40, 95% CI: 1.26-4.50) and (iv) age >=75 years (OR: 2.12, 95% CI: 1.23-3.70).
      CONCLUSION: the GerontoNet ADR risk score incorrectly classified 38% of patients
      as low risk. Inappropriate medications and increasing age also contribute to ADR
      risk.

PMID- 22456467
TI  - Asymmetric catalysts for stereocontrolled olefin metathesis reactions.
AB  - Since the discovery of metathesis as an instrument to reorganize olefinic double
      bonds, substantial progress has been attained, establishing this method as a
      versatile and efficient tool for C-C-bond formation. In the last decade
      fundamental achievements were accomplished in the field of chiral Ru- and Mo
      based olefin metathesis, providing an asymmetric access to structures, which are
      difficult to obtain by alternative routes. The reader is taken behind the scenes
      of catalyst development, important areas of application are described up to the
      current state of research; this tutorial review deals with the question, how
      metathesis is connected to enantioselective synthesis.

PMID- 22456466
TI  - Inflammatory regulators of redirected neural migration in the injured brain.
AB  - Brain injury following stroke or trauma induces the migration of neuroblasts
      derived from subventricular zone neural precursor cells (NPCs) towards the
      damaged tissue, where they then have the potential to contribute to repair.
      Enhancing the recruitment of new cells thus presents an enticing prospect for the
      development of new therapeutic approaches to treat brain injury; to this end, an
      understanding of the factors regulating this process is required. During the
      neuroinflammatory response to ischemic and traumatic brain injuries, a plethora
      of pro- and anti-inflammatory cytokines, chemokines and growth factors are
      released in the damaged tissue, and recent work indicates that a variety of these
      are able to influence injury-induced migration. In this review, we will discuss
      the contribution of specific chemokines and growth factors towards stimulating
      NPC migration in the injured brain.

PMID- 22456469
TI  - Takayasu arteritis presenting with internal carotid artery dissection.

PMID- 22456468
TI  - Pioglitazone prevents capillary rarefaction in streptozotocin-diabetic rats
      independently of glucose control and vascular endothelial growth factor
      expression.
AB  - BACKGROUND/AIMS: Reduction of capillary network density occurs early in the
      development of metabolic syndrome and may be relevant for the precipitation of
      diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma
      transcription factor are vasculoprotective, but their capacity for structural
      preservation of the microcirculation is unclear. METHODS: Male Wistar rats were
      rendered diabetic by streptozotocin and treated with pioglitazone in chow for up
      to 12 weeks. Capillary density was determined in heart and skeletal muscle after
      platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks
      of apoptosis and angiogenesis were determined. RESULTS: Capillary density
      deteriorated progressively in the presence of hyperglycemia (from 971/mm2 to
      475/mm2 in quadriceps muscle during 13 weeks). Pioglitazone did not influence
      plasma glucose, left ventricular weight, or body weight but nearly doubled
      absolute and relative capillary densities compared to untreated controls (1.2 vs.
      0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in
      quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic
      influence of pioglitazone was detected while a reduced expression of hypoxia
      inducible factor-3alpha and PPAR coactivator-1alpha (PGC-1alpha) mRNA as well as
      vascular endothelial growth factor (VEGF) protein possibly occurred as a
      consequence of improved vascularization. CONCLUSION: Pioglitazone preserves
      microvascular structure in diabetes independently of improvements in glycemic
      control and by a mechanism unrelated to VEGF-mediated angiogenesis.

PMID- 22456470
TI  - Sunlight induced cycloaddition and host-guest property of self-assembled
      organometallic macrocycles based on a versatile building block.
AB  - Organometallic rectangle 1 which undergoes [2+2] cycloaddition upon irradiation
      with sunlight and organometallic prism 3 which displayed interesting host-guest
      property were self-assembled based on a versatile building block.

PMID- 22456471
TI  - NMR in natural products: understanding conformation, configuration and receptor
      interactions.
AB  - Covering: up to 2011. Natural products are of tremendous importance in both
      traditional and modern medicine. For medicinal chemistry natural products
      represent a challenge, as their chemical synthesis and modification are complex
      processes, which require many, often stereo-selective, synthetic steps. A
      prerequisite for the design of analogs of natural products, with more accessible
      synthetic routes, is the availability of their bioactive conformation. Nuclear
      Magnetic Resonance (NMR) spectroscopy and X-ray crystallography are the two
      techniques of choice to investigate the structure of natural products. In this
      review, I describe the most recent advances in NMR to study the conformation of
      natural products either free in solution or bound to their cellular receptors. In
      chapter 2, I focus on the use of residual dipolar couplings (RDC). On the basis
      of a few examples, I discuss the benefit of complementing classical NMR
      parameters, such as NOEs and scalar couplings, with dipolar couplings to
      simultaneously determine both the conformation and the relative configuration of
      natural products in solution. Chapter 3 is dedicated to the study of the
      structure of natural products in complex with their cellular receptors and is
      further divided in two sections. In the first section, I describe two solution
      state NMR methodologies to investigate the binding mode of low-affinity ligands
      to macromolecular receptors. The first approach, INPHARMA (Interligand Noes for
      PHArmacophore Mapping), is based on the observation of interligand NOEs between
      two small molecules binding competitively to a common receptor. INPHARMA reveals
      the relative binding mode of the two ligands, thus allowing ligand
      superimposition. The second approach is based on paramagnetic relaxation
      enhancement (PRE) of ligand resonances in the presence of a receptor containing a
      paramagnetic center. In the second section, I focus on solid-state NMR
      spectroscopy as a tool to access the bioactive conformation of natural products
      in complex with macromolecular receptors.

PMID- 22456472
TI  - Long-term outcomes of mechanical valve replacement in patients with atrial
      fibrillation: impact of the maze procedure.
AB  - BACKGROUND: The long-term benefits of the maze procedure in patients with chronic
      atrial fibrillation undergoing mechanical valve replacement who already require
      lifelong anticoagulation remain unclear. METHODS AND RESULTS: We evaluated
      adverse outcomes (death; thromboembolic events; composite of death, heart
      failure, or valve-related complications) in 569 patients with atrial fibrillation
      associated valvular heart disease who underwent mechanical valve replacement with
      (n=317) or without (n=252) a concomitant maze procedure between 1999 and 2010.
      After adjustment for differences in baseline risk profiles, patients who had
      undergone the maze procedure were at similar risks of death (hazard ratio, 1.15;
      95% confidence interval, 0.65-2.03; P=0.63) and the composite outcomes (hazard
      ratio, 0.82; 95% confidence interval, 0.50-1.34; P=0.42) but a significantly
      lower risk of thromboembolic events (hazard ratio, 0.29; 95% confidence interval,
      0.12-0.73; P=0.008) compared with those who underwent valve replacement alone at
      a median follow-up of 63.6 months (range, 0.2-149.9 months). The effect of
      superior event-free survival by the concomitant maze procedure was notable in a
      low-risk EuroSCORE (0-3) subgroup (P=0.049), but it was insignificant in a high
      risk EuroSCORE (>=4) subgroup (P=0.65). Furthermore, the combination of the maze
      procedure resulted in superior left ventricular (P<0.001) and tricuspid valvular
      functions (P<0.001) compared with valve replacement alone on echocardiographic
      assessments performed at a median of 52.7 months (range, 6.0-146.8 months) after
      surgery. CONCLUSION: Compared with valve replacement alone, the addition of the
      maze procedure was associated with a reduction in thromboembolic complications
      and improvements in hemodynamic performance in patients undergoing mechanical
      valve replacement, particularly in those with low risk of surgery.

PMID- 22456473
TI  - Multiple biomarkers and risk of clinical and subclinical vascular brain injury:
      the Framingham Offspring Study.
AB  - BACKGROUND: Several biomarkers have been individually associated with vascular
      brain injury, but no prior study has explored the simultaneous association of a
      biologically plausible panel of biomarkers with the incidence of stroke/transient
      ischemic attack and the prevalence of subclinical brain injury. METHODS AND
      RESULTS: In 3127 stroke-free Framingham offspring (age, 59+/-10 years; 54%
      female), we related a panel of 8 biomarkers assessing inflammation (C-reactive
      protein), hemostasis (D-dimer and plasminogen activator inhibitor-1),
      neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide,
      and N-terminal proatrial natriuretic peptides), and endothelial function
      (homocysteine and urinary albumin/creatinine ratio) measured at the sixth
      examination (1995-1998) to risk of incident stroke/transient ischemic attack. In
      a subset of 1901 participants with available brain magnetic resonance imaging
      (1999-2005), we further related these biomarkers to total cerebral brain volume,
      covert brain infarcts, and large white-matter hyperintensity volume. During a
      median follow-up of 9.2 years, 130 participants experienced incident
      stroke/transient ischemic attack. In multivariable analyses adjusted for stroke
      risk factors, the biomarker panel was associated with incident stroke/transient
      ischemic attack and with total cerebral brain volume (P<0.05 for both) but not
      with covert brain infarcts or white-matter hyperintensity volume (P>0.05). In
      backward elimination analyses, higher log-B-type natriuretic peptide (hazard
      ratio, 1.39 per 1-SD increment; P=0.002) and log-urinary albumin/creatinine ratio
      (hazard ratio, 1.31 per 1-SD increment; P=0.004) were associated with increased
      risk of stroke/transient ischemic attack and improved risk prediction compared
      with the Framingham Stroke Risk Profile alone; when the <5%, 5% to 15%, or >15%
      10-year risk category was used, the net reclassification index was 0.109
      (P=0.037). Higher C-reactive protein (beta=-0.21 per 1-SD increment; P=0.008), D
      dimer (beta=-0.18 per 1-SD increment; P=0.041), total homocysteine (beta=-0.21
      per 1-SD increment; P=0.005), and urinary albumin/creatinine ratio (beta=-0.15
      per 1-SD increment; P=0.042) were associated with lower total cerebral brain
      volume. CONCLUSION: In a middle-aged community sample, we identified multiple
      biomarkers that were associated with clinical and subclinical vascular brain
      injury and could improve risk stratification.

PMID- 22456474
TI  - Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger
      function underlie delayed afterdepolarizations in patients with chronic atrial
      fibrillation.
AB  - BACKGROUND: Delayed afterdepolarizations (DADs) carried by Na(+)-Ca(2+)-exchange
      current (I(NCX)) in response to sarcoplasmic reticulum (SR) Ca(2+) leak can
      promote atrial fibrillation (AF). The mechanisms leading to delayed
      afterdepolarizations in AF patients have not been defined. METHODS AND RESULTS:
      Protein levels (Western blot), membrane currents and action potentials (patch
      clamp), and [Ca(2+)](i) (Fluo-3) were measured in right atrial samples from 76
      sinus rhythm (control) and 72 chronic AF (cAF) patients. Diastolic [Ca(2+)](i)
      and SR Ca(2+) content (integrated I(NCX) during caffeine-induced Ca(2+)
      transient) were unchanged, whereas diastolic SR Ca(2+) leak, estimated by
      blocking ryanodine receptors (RyR2) with tetracaine, was ~50% higher in cAF
      versus control. Single-channel recordings from atrial RyR2 reconstituted into
      lipid bilayers revealed enhanced open probability in cAF samples, providing a
      molecular basis for increased SR Ca(2+) leak. Calmodulin expression (60%),
      Ca(2+)/calmodulin-dependent protein kinase-II (CaMKII) autophosphorylation at
      Thr287 (87%), and RyR2 phosphorylation at Ser2808 (protein kinase A/CaMKII site,
      236%) and Ser2814 (CaMKII site, 77%) were increased in cAF. The selective CaMKII
      blocker KN-93 decreased SR Ca(2+) leak, the frequency of spontaneous Ca(2+)
      release events, and RyR2 open probability in cAF, whereas protein kinase A
      inhibition with H-89 was ineffective. Knock-in mice with constitutively
      phosphorylated RyR2 at Ser2814 showed a higher incidence of Ca(2+) sparks and
      increased susceptibility to pacing-induced AF compared with controls. The
      relationship between [Ca(2+)](i) and I(NCX) density revealed I(NCX) upregulation
      in cAF. Spontaneous Ca(2+) release events accompanied by inward I(NCX) currents
      and delayed afterdepolarizations/triggered activity occurred more often and the
      sensitivity of resting membrane voltage to elevated [Ca(2+)](i) (diastolic
      [Ca(2+)](i)-voltage coupling gain) was higher in cAF compared with control.
      CONCLUSIONS: Enhanced SR Ca(2+) leak through CaMKII-hyperphosphorylated RyR2, in
      combination with larger I(NCX) for a given SR Ca(2+) release and increased
      diastolic [Ca(2+)](i)-voltage coupling gain, causes AF-promoting atrial delayed
      afterdepolarizations/triggered activity in cAF patients.

PMID- 22456476
TI  - Meandering pathway leading from genotyping to personalized management of long-QT
      syndrome.

PMID- 22456477
TI  - Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life
      threatening events: implications for mutation-specific response to beta-blocker
      therapy in type 1 long-QT syndrome.
AB  - BACKGROUND: beta-Adrenergic stimulation is the main trigger for cardiac events in
      type 1 long-QT syndrome (LQT1). We evaluated a possible association between ion
      channel response to beta-adrenergic stimulation and clinical response to beta
      blocker therapy according to mutation location. METHODS AND RESULTS: The study
      sample comprised 860 patients with genetically confirmed mutations in the KCNQ1
      channel. Patients were categorized into carriers of missense mutations located in
      the cytoplasmic loops (C loops), membrane-spanning domain, C/N terminus, and
      nonmissense mutations. There were 27 aborted cardiac arrest and 78 sudden cardiac
      death events from birth through 40 years of age. After multivariable adjustment
      for clinical factors, the presence of C-loop mutations was associated with the
      highest risk for aborted cardiac arrest or sudden cardiac death (hazard ratio
      versus nonmissense mutations=2.75; 95% confidence interval, 1.29-5.86; P=0.009).
      beta-Blocker therapy was associated with a significantly greater reduction in the
      risk of aborted cardiac arrest or sudden cardiac death among patients with C-loop
      mutations than among all other patients (hazard ratio=0.12; 95% confidence
      interval, 0.02-0.73; P=0.02; and hazard ratio=0.82; 95% confidence interval, 0.31
      2.13; P=0.68, respectively; P for interaction=0.04). Cellular expression studies
      showed that membrane spanning and C-loop mutations produced a similar decrease in
      current, but only C-loop mutations showed a pronounced reduction in channel
      activation in response to beta-adrenergic stimulation. CONCLUSIONS: Patients with
      C-loop missense mutations in the KCNQ1 channel exhibit a high risk for life
      threatening events and derive a pronounced benefit from treatment with beta
      blockers. Reduced channel activation after sympathetic activation can explain the
      increased clinical risk and response to therapy in patients with C-loop
      mutations.

PMID- 22456479
TI  - Ruthenium-catalyzed intramolecular cyclization of diazo-beta-ketoanilides for the
      synthesis of 3-alkylideneoxindoles.
AB  - With [Ru(p-cymene)Cl(2)](2) as catalyst, diazo-beta-ketoanilides would undergo
      intramolecular carbenoid arene C-H bond functionalization to afford 3
      alkylideneoxindoles in up to 92% yields. The reaction occurs under mild
      conditions and exhibits excellent chemoselectivity. The lack of primary KIE
      (k(H)/k(D) ~ 1) suggests that the reaction should not proceed by rate-limiting C
      H bond cleavage; a mechanism involving cyclopropanation of the arene is proposed.

PMID- 22456478
TI  - Late results of percutaneous mitral commissurotomy up to 20 years: development
      and validation of a risk score predicting late functional results from a series
      of 912 patients.
AB  - BACKGROUND: Long-term follow-up after percutaneous mitral commissurotomy enables
      predictive factors of late results to be identified. METHODS AND RESULTS: Late
      results of percutaneous mitral commissurotomy were assessed in 1024 consecutive
      patients. Good immediate results, defined as valve area >=1.5 cm(2) without
      mitral regurgitation >2/4, were obtained in 912 patients (89%). These 912
      patients were randomly split into 2 cohorts comprising 609 and 303 patients that
      were used to develop and validate, respectively, a scoring system predicting late
      functional results. The 20-year rate of good functional results (survival without
      cardiovascular death, mitral surgery, or repeat percutaneous mitral
      commissurotomy and in New York Heart Association class I or II) was 30.2 +/-
      2.0%. A multivariable Cox model identified 7 predictive factors of poor late
      functional results: higher final mean gradient (P<0.0001), interaction between
      age and final mitral valve area (P<0.0001) showing that the impact of valve area
      decreases with age, interaction between sex and valve calcification (P<0.0001)
      showing that the impact of valve anatomy is stronger in men, and interaction
      between rhythm and New York Heart Association class showing an impact of New York
      Heart Association class only in patients in atrial fibrillation (P<0.0001). A 13
      point score enabled 3 risk groups to be defined, corresponding to predicted good
      functional results of 55.1%, 29.1%, and 10.5% at 20 years in the validation
      cohort. CONCLUSIONS: Twenty years after percutaneous mitral commissurotomy in a
      population of patients with varied characteristics, 30% still had good functional
      results. Prediction of late functional results is multifactorial and strongly
      determined by age and the quality of immediate results. A simple validated
      scoring system is useful for estimating individual patient outcome.

PMID- 22456480
TI  - Genetic differences in the two main groups of the Japanese population based on
      autosomal SNPs and haplotypes.
AB  - Although the Japanese population has a rather low genetic diversity, we recently
      confirmed the presence of two main clusters (the Hondo and Ryukyu clusters)
      through principal component analysis of genome-wide single-nucleotide
      polymorphism (SNP) genotypes. Understanding the genetic differences between the
      two main clusters requires further genome-wide analyses based on a dense SNP set
      and comparison of haplotype frequencies. In the present study, we determined
      haplotypes for the Hondo cluster of the Japanese population by detecting SNP
      homozygotes with 388,591 autosomal SNPs from 18,379 individuals and estimated the
      haplotype frequencies. Haplotypes for the Ryukyu cluster were inferred by a
      statistical approach using the genotype data from 504 individuals. We then
      compared the haplotype frequencies between the Hondo and Ryukyu clusters. In most
      genomic regions, the haplotype frequencies in the Hondo and Ryukyu clusters were
      very similar. However, in addition to the human leukocyte antigen region on
      chromosome 6, other genomic regions (chromosomes 3, 4, 5, 7, 10 and 12) showed
      dissimilarities in haplotype frequency. These regions were enriched for genes
      involved in the immune system, cell-cell adhesion and the intracellular signaling
      cascade. These differentiated genomic regions between the Hondo and Ryukyu
      clusters are of interest because they (1) should be examined carefully in
      association studies and (2) likely contain genes responsible for morphological or
      physiological differences between the two groups.

PMID- 22456481
TI  - Novel TARDBP mutations in Nordic ALS patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative syndrome primarily
      affecting the upper and lower motor neurons. A characteristic neuropathological
      finding in ALS patients is neuronal inclusions positive for TAR DNA-binding
      protein 43 (TDP-43). Subsequently, mutations in the gene encoding TDP-43, TARDBP,
      proved to be involved in the development of ALS. We thus sequenced TARDBP in 177
      Nordic ALS patients and found two previously reported (p.A90V and p.S379P) and
      two novel (p.G357R and p.R361T) missense variations in three familial ALS
      patients. The p.A90V and p.G357R variations were detected in the same patient and
      p.R361T was present in a family with both ALS and frontotemporal dementia-ALS.
      None of the missense variations were present in 200 neurologically healthy
      controls. However, p.A90V has also been reported in healthy individuals by
      others. Thus, the data suggest that these variations are rare and p.G357R,
      p.R361T and p.S379P are likely pathogenic but further functional characterization
      is needed to prove their pathogenicity. The mutation frequency in TARDBP in
      Nordic ALS patients was 1.7%. The ALS cohort was highly selected for a positive
      family history suggesting that mutations in TARDBP generally are a rare cause of
      ALS in Nordic countries.

PMID- 22456475
TI  - Early developmental outcome in children with hypoplastic left heart syndrome and
      related anomalies: the single ventricle reconstruction trial.
AB  - BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental
      impairment. Clinical trials to improve outcomes have focused primarily on methods
      of vital organ support during cardiopulmonary bypass. METHODS AND RESULTS: In the
      Single Ventricle Reconstruction trial of the Norwood procedure with modified
      Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month
      neurodevelopmental outcome was assessed by use of the Psychomotor Development
      Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant
      Development-II. We used multivariable regression to identify risk factors for
      adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age
      14.3 +/- 1.1 (mean +/- SD) months. Mean PDI (74 +/- 19) and MDI (89 +/- 18)
      scores were lower than normative means (each P<0.001). Neither PDI nor MDI score
      was associated with type of Norwood shunt. Independent predictors of lower PDI
      score (R(2)=26%) were clinical center (P=0.003), birth weight <2.5 kg (P=0.023),
      longer Norwood hospitalization (P<0.001), and more complications between Norwood
      procedure discharge and age 12 months (P<0.001). Independent risk factors for
      lower MDI score (R(2)=34%) included center (P<0.001), birth weight <2.5 kg
      (P=0.04), genetic syndrome/anomalies (P=0.04), lower maternal education (P=0.04),
      longer mechanical ventilation after the Norwood procedure (P<0.001), and more
      complications after Norwood discharge to age 12 months (P<0.001). We found no
      significant relationship of PDI or MDI score to perfusion type, other aspects of
      vital organ support (eg, hematocrit, pH strategy), or cardiac anatomy.
      CONCLUSIONS: Neurodevelopmental impairment in Norwood survivors is more highly
      associated with innate patient factors and overall morbidity in the first year
      than with intraoperative management strategies. Improved outcomes are likely to
      require interventions that occur outside the operating room. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

PMID- 22456482
TI  - Phenotype variations in Lafora progressive myoclonus epilepsy: possible
      involvement of genetic modifiers?
AB  - Lafora progressive myoclonus epilepsy, also known as Lafora disease (LD), is the
      most severe and fatal form of progressive myoclonus epilepsy with its typical
      onset during the late childhood or early adolescence. LD is characterized by
      recurrent epileptic seizures and progressive decline in intellectual function. LD
      can be caused by defects in any of the two known genes and the clinical features
      of these two genetic groups are almost identical. The past one decade has
      witnessed considerable success in identifying the LD genes, their mutations, the
      cellular functions of gene products and on molecular basis of LD. Here, we
      briefly review the current literature on the phenotype variations, on possible
      presence of genetic modifiers, and candidate modifiers as targets for therapeutic
      interventions in LD.

PMID- 22456484
TI  - Summary of the British Transplantation Society/Renal Association U.K. guidelines
      for living donor kidney transplantation.
AB  - The third edition of the joint British Transplantation Society/Renal Association
      guidelines for living donor kidney transplantation was published in May 2011. The
      guideline has been extensively revised since the previous edition in 2005 and has
      used the GRADE system to rate the strength of evidence and recommendations. This
      article summarizes the statements of recommendation contained in the guideline,
      which provide a framework for the delivery of living kidney donation in the
      United Kingdom and may be of wide international interest. It is recommended that
      the full guideline document is consulted for details of the relevant references
      and evidence base. This may be accessed at
      http://www.bts.org.uk/transplantation/standards-and-guidelines/ and
      http://www.renal.org/clinical/OtherGuidelines.aspx (transplantation is welcome to
      add a web link in this article to/through its own Web site to increase traffic).

PMID- 22456485
TI  - Changing stripes to avoid graft versus leukemia.

PMID- 22456486
TI  - Endothelial chimerism after ABO-incompatible kidney transplantation.
AB  - BACKGROUND: Endothelial chimerism in transplanted organs can be defined as the
      presence of recipient-derived endothelial cells in the donor organ. The mechanism
      of endothelial chimerism is not well understood and remains controversial. The
      purpose of this study was twofold. First, we investigated the presence of
      chimerism in renal allografts of ABO-incompatible kidney transplantation
      recipients. Second, we analyzed the association between chimerism and the
      clinical course and histopathological changes. METHODS: We investigated the
      presence of chimerism in renal allografts of ABO-incompatible kidney
      transplantation recipients by immunohistochemical detection of blood type A and B
      antigens and assessed the association between chimerism, the clinical course, and
      histopathological changes. Among a total of 56 patients (29 blood group A
      incompatible and 27 blood group B incompatible), 49 cases (28 blood group A
      incompatible and 21 blood group B incompatible) were enrolled in this study.
      Blood group antigens were stained using immunohistochemistry. RESULTS: Twelve of
      the 49 patients (12/49, 24.5%) exhibited endothelium chimerism in a biopsy
      sample. Among the 12 patients with endothelium chimerism, 7 patients (7/12, 59%)
      had acute and chronic active antibody-mediated rejection and 2 patients (2/12,
      17%) had severe calcineurin inhibitor toxicity. The graft survival rate in the
      chimerism group was significantly lower than that in the no-chimerism group
      ([chimerism vs. no-chimerism] 3 years, 83.3% vs. 97.1%; 5 years, 74.1% vs. 97.1%;
      8 years, 46.3% vs. 97.1%; P<0.0001). CONCLUSIONS: Endothelial chimerism seems to
      be a hallmark of vigorous immune or nonimmune responses, such as antibody
      mediated rejection or calcineurin inhibitor toxicity, and not of the induction of
      tolerance.

PMID- 22456483
TI  - Ether- and alcohol-functionalized task-specific ionic liquids: attractive
      properties and applications.
AB  - In recent years, the designer nature of ionic liquids (ILs) has driven their
      exploration and exploitation in countless fields among the physical and chemical
      sciences. A fair measure of the tremendous attention placed on these fluids has
      been attributed to their inherent designer nature. And yet, there are relatively
      few examples of reviews that emphasize this vital aspect in an exhaustive or
      meaningful way. In this critical review, we systematically survey the
      physicochemical properties of the collective library of ether- and alcohol
      functionalized ILs, highlighting the impact of ionic structure on features such
      as viscosity, phase behavior/transitions, density, thermostability,
      electrochemical properties, and polarity (e.g. hydrophilicity, hydrogen bonding
      capability). In the latter portions of this review, we emphasize the attractive
      applications of these functionalized ILs across a range of disciplines, including
      their use as electrolytes or functional fluids for electrochemistry, extractions,
      biphasic systems, gas separations, carbon capture, carbohydrate dissolution
      (particularly, the (ligno)celluloses), polymer chemistry, antimicrobial and
      antielectrostatic agents, organic synthesis, biomolecular stabilization and
      activation, and nanoscience. Finally, this review discusses anion-functionalized
      ILs, including sulfur- and oxygen-functionalized analogs, as well as choline
      based deep eutectic solvents (DESs), an emerging class of fluids which can be
      sensibly categorized as semi-molecular cousins to the IL. Finally, the toxicity
      and biodegradability of ether- and alcohol-functionalized ILs are discussed and
      cautiously evaluated in light of recent reports. By carefully summarizing
      literature examples on the properties and applications of oxy-functional designer
      ILs up till now, it is our intent that this review offers a barometer for gauging
      future advances in the field as well as a trigger to spur further contemplation
      of these seemingly inexhaustible and--relative to their potential--virtually
      untouched fluids. It is abundantly clear that these remarkable fluidic materials
      are here to stay, just as certain design rules are slowly beginning to emerge.
      However, in fairness, serendipity also still plays an undeniable role,
      highlighting the need for both expanded in silico studies and a beacon to attract
      bright, young researchers to the field (406 references).

PMID- 22456487
TI  - Child sexual behavior inventory: a comparison between Latino and normative
      samples of preschoolers.
AB  - There is a relative dearth of research examining normative sexual behavior in
      Latino preschool children, despite an increased presence of Latinos as a minority
      population in the United States. To meet this need, a sample of Latino mothers
      were asked to complete the Child Sexual Behavior Inventory (CSBI; Friedrich et
      al., 1992 ) on their preschool-aged children (3 to 5 years old; n = 188). When
      their children's scores were compared to CSBI normative data, significant
      differences emerged. Compared to the normative sample, Latino boys and girls
      scored significantly higher on the sexual abuse specific items subscale, and
      Latino girls scored significantly higher on the developmentally related sexual
      behavior subscale. Possible cultural explanations for these elevations are
      explored.

PMID- 22456488
TI  - Chronological change in pulmonary vascular response to hypoxia in hepatopulmonary
      syndrome.
AB  - Here we present a case of hepatopulmonary syndrome (HPS) where spontaneous
      resolution of severe hypoxaemia occurred with the development of pulmonary
      hypertension over several years after the initial diagnosis of HPS. The pulmonary
      vascular responses to hypoxia examined before and after the spontaneous
      resolution of HPS confirmed that the pathogenesis of HPS could be functional and
      reversible in nature. To the best of our knowledge, this is the first report
      demonstrating a remarkable change in the pulmonary vascular response to hypoxia
      before and after the spontaneous resolution of hypoxaemia in HPS.

PMID- 22456489
TI  - Optimization of a heterologous signal peptide by site-directed mutagenesis for
      improved secretion of recombinant proteins in Escherichia coli.
AB  - A heterologous signal peptide (SP) from Bacillus sp. G1 was optimized for
      secretion of recombinant cyclodextrin glucanotransferase (CGTase) to the
      periplasmic and, eventually, extracellular space of Escherichia coli. Eight
      mutant SPs were constructed using site-directed mutagenesis to improve the
      secretion of recombinant CGTase. M5 is a mutated SP in which replacement of an
      isoleucine residue in the h-region to glycine created a helix-breaking or G-turn
      motif with decreased hydrophobicity. The mutant SP resulted in 110 and 94%
      increases in periplasmic and extracellular recombinant CGTase, respectively,
      compared to the wild-type SP at a similar level of cell lysis. The formation of
      intracellular inclusion bodies was also reduced, as determined by sodium dodecyl
      sulfate-polyacrylamyde gel electrophoresis, when this mutated SP was used. The
      addition of as low as 0.08% glycine at the beginning of cell growth improved cell
      viability of the E. coli host. Secretory production of other proteins, such as
      mannosidase, also showed similar improvement, as demonstrated by CGTase
      production, suggesting that the combination of an optimized SP and a suitable
      chemical additive leads to significant improvements of extracellular recombinant
      protein production and cell viability. These findings will be valuable for the
      extracellular production of recombinant proteins in E. coli.

PMID- 22456490
TI  - An infant with a unilateral mandibular fracture: when to consider nonaccidental
      trauma.

PMID- 22456491
TI  - Current national patterns of comorbid diabetes among acute ischemic stroke
      patients.
AB  - BACKGROUND: Type 2 diabetes rates in the general population have risen with the
      growing obesity epidemic. Knowledge of temporal patterns and factors associated
      with comorbid diabetes among stroke patients may enable health practitioners and
      policy makers to develop interventions aimed at reducing diabetes rates, which
      may consequently lead to declines in stroke incidence and improvements in stroke
      outcomes. METHODS: Using the Nationwide Inpatient Sample (NIS), a nationally
      representative data set of US hospital admissions, we assessed trends in the
      proportion of acute ischemic stroke (AIS) patients with comorbid diabetes from
      1997 to 2006. Independent factors associated with comorbid diabetes were
      evaluated using multivariable logistic regression. RESULTS: Over the study
      period, the absolute number of AIS hospitalizations declined by 17% (from 489,766
      in 1997 to 408,378 in 2006); however, the absolute number of AIS hospitalizations
      with comorbid type 2 diabetes rose by 27% [from 97,577 (20%) in 1997 to 124,244
      (30%) in 2006, p < 0.001]. The rise in comorbid diabetes over time was more
      pronounced in patients who were relatively younger, Black or 'other' race, on
      Medicaid, or admitted to hospitals located in the South. Factors independently
      associated with higher odds of diabetes in AIS patients were Black or 'other'
      versus White race, congestive heart failure, peripheral vascular disease, history
      of myocardial infarction, renal disease and hypertension. CONCLUSIONS: Although
      hospitalizations for AIS in the US decreased from 1997 to 2006, there was a steep
      rise in the proportion with comorbid diabetes (from 1 in 5 to almost 1 in 3).
      Specific patient populations may be potential targets for mitigating this trend.

PMID- 22456492
TI  - Use of cognitive enhancement medication among northern Italian university
      students.
AB  - This study assesses the use of cognitive enhancement medication among university
      students in Northern Italy. It was conducted as a cross-sectional analysis on the
      basis of a paper-and-pencil survey of 77 undergraduate students attending courses
      in the Faculty of Medicine of the University of Milan, Milano, Italy. Although
      the share of students who have taken cognitive enhancement medication themselves
      in the past is still small (16%), the use of these drugs is rather common and
      freely communicated in some social circles. Enhancing the ability to study
      outside of the class was students' primary motive for use. Students who think
      that there is no or an acceptable risk involved in cognitive enhancement
      medication are more likely to take drugs and dietary supplements than those who
      perceive the risk as high.

PMID- 22456493
TI  - Double successful buprenorphine/naloxone induction to facilitate cardiac
      transplantation in an iatrogenically opiate-dependent patient.
AB  - Buprenorphine/naloxone is used for the treatment of opioid dependence. In the
      following case, a potential use for the medication combination is explored in the
      arena of transplant surgery. Psychiatry was consulted for a 29-year-old woman
      with iatrogenic opioid dependence after bilateral ventricular assist device
      placement for congenital cardiomyopathy. Her ejection fraction was less than 15%
      and she was considered a poor candidate for transplant due to drug-seeking
      behaviors. We transitioned her onto buprenorphine/naloxone to prevent abuse and
      control symptoms, qualifying her for cardiac transplant. After transplant, we
      coordinated care with cardiothoracic surgeons to restart buprenorphine/naloxone,
      and the patient has been stable for 8 months.

PMID- 22456495
TI  - Dense scents of nature.

PMID- 22456496
TI  - Interaction between single gold atom and the graphene edge: a study via
      aberration-corrected transmission electron microscopy.
AB  - Interaction between single noble metal atoms and graphene edges has been
      investigated via aberration-corrected and monochromated transmission electron
      microscopy. A collective motion of the Au atom and the nearby carbon atoms is
      observed in transition between energy-favorable configurations. Most trapping and
      detrapping processes are assisted by the dangling carbon atoms, which are more
      susceptible to knock-on displacements by electron irradiation. Thermal energy is
      lower than the activation barriers in transition among different energy-favorable
      configurations, which suggests electron-beam irradiation can be an efficient way
      of engineering the graphene edge with metal atoms.

PMID- 22456494
TI  - Estimated global mortality attributable to smoke from landscape fires.
AB  - BACKGROUND: Forest, grass, and peat fires release approximately 2 petagrams of
      carbon into the atmosphere each year, influencing weather, climate, and air
      quality. OBJECTIVE: We estimated the annual global mortality attributable to
      landscape fire smoke (LFS). METHODS: Daily and annual exposure to particulate
      matter <= 2.5 MUm in aerodynamic diameter (PM(2.5)) from fire emissions was
      estimated globally for 1997 through 2006 by combining outputs from a chemical
      transport model with satellite-based observations of aerosol optical depth. In
      World Health Organization (WHO) subregions classified as sporadically affected,
      the daily burden of mortality was estimated using previously published
      concentration-response coefficients for the association between short-term
      elevations in PM(2.5) from LFS (contrasted with 0 MUg/m3 from LFS) and all-cause
      mortality. In subregions classified as chronically affected, the annual burden of
      mortality was estimated using the American Cancer Society study coefficient for
      the association between long-term PM(2.5) exposure and all-cause mortality. The
      annual average PM(2.5) estimates were contrasted with theoretical minimum
      (counterfactual) concentrations in each chronically affected subregion.
      Sensitivity of mortality estimates to different exposure assessments,
      counterfactual estimates, and concentration-response functions was evaluated.
      Strong La Nina and El Nino years were compared to assess the influence of
      interannual climatic variability. RESULTS: Our principal estimate for the average
      mortality attributable to LFS exposure was 339,000 deaths annually. In
      sensitivity analyses the interquartile range of all tested estimates was 260,000
      600,000. The regions most affected were sub-Saharan Africa (157,000) and
      Southeast Asia (110,000). Estimated annual mortality during La Nina was 262,000,
      compared with 532,000 during El Nino. CONCLUSIONS: Fire emissions are an
      important contributor to global mortality. Adverse health outcomes associated
      with LFS could be substantially reduced by curtailing burning of tropical
      rainforests, which rarely burn naturally. The large estimated influence of El
      Nino suggests a relationship between climate and the burden of mortality
      attributable to LFS.

PMID- 22456497
TI  - One-pot synthesis of 4-substituted isoquinolinium zwitterionic salts by metal
      free C-H bond activation.
AB  - The unprecedented isoquinolinium zwitterionic salts with an unusual C-4
      substitution pattern were efficiently prepared via the multicomponent reaction of
      in situ formed N-benzylisoquinolinium bromide with aromatic aldehydes and cyclic
      1,3-dicarbonyl compounds.

PMID- 22456499
TI  - The all non-metal homodinuclear and heterodinuclear sandwich-like compounds
      C2(eta3-L3)2 and BN(eta3-L3)2 (L = BCO, BNN and CBO).
AB  - Density functional theory studies on the all non-metal homodinuclear and
      heterodinuclear sandwich-like compounds C(2)(eta(3)-L(3))(2) and BN(eta(3)
      L(3))(2) (L = BCO, BNN and CBO) have been performed. The staggered conformations
      of both C(2)(eta(3)-L(3))(2) and BN(eta(3)-L(3))(2) are predicted to be stable.
      The non-metal direct C-C and B-N bonds are covalent with sigma interactions,
      which are formed by the interactions of s and p(z) orbitals of the center atoms.
      Different from the ionic metal-ligand bond in the traditional metal center
      sandwich-like compounds, the C-L, B-L, and N-L bonds are covalent in these all
      non-metal sandwich-like compounds. The NICS values indicate that the ligands of
      C(2)(eta(3)-L(3))(2) and BN(eta(3)-L(3))(2), as well as their bare rings, display
      multiple aromaticity (sigma and pi aromaticity). Both sigma and pi aromaticity of
      the ring ligands towards the center atoms become stronger after complexation with
      the center atoms, while the pi aromaticity against the center atoms is reduced.
      The pi aromaticity of the ligands bonded to different center atoms follows a
      trend of B > C > N, and the (CBO)(3)(+) ligands bonded to B possess the strongest
      pi aromaticity. The dissociation reactions and possible synthetic reactions
      analysis show that these all non-metal sandwich-like compounds are stable, and
      the homodinuclear species are more stable than the heterodinuclear ones. These
      all non-metal binuclear sandwich-like compounds can be regarded as potential
      synthetic targets according to the highly negative free energies of the possible
      synthetic reactions. The isomerization reactions demonstrate that the CBO-based
      compounds should be more possible to synthesize in experiments than their BCO
      based isomers.

PMID- 22456498
TI  - Infectious (Non)tolerance--frustrated commensalism gone awry?
AB  - Despite advances in medicine, infectious diseases remain major causes of death
      and disability worldwide. Acute or chronic infectious agents mediate host tissue
      damage and cause a spectrum of disease as diverse as overwhelming sepsis and
      shock within hours to persistent tissue inflammation causing organ failure or
      even cancer over years. Although pathogen exposure can cause disease via host
      derived inflammation, pathogens share recognized elements with harmless human
      commensals. Mouse models and organisms with simpler flora are revealing the
      dialogue between multicellular hosts and commensal flora. In some instances the
      persistent inflammation associated with pathogens can be interpreted within a
      framework of frustrated commensalism in which the host and pathogen cannot
      complete the requisite dialogue that establishes homeostasis. In contrast,
      coevolved commensals interact cooperatively with the host immune system,
      resulting in immunotolerance. Attempts to more thoroughly understand the
      molecular nature of the dialogue may uncover novel approaches to the control of
      inflammation and tissue damage.

PMID- 22456500
TI  - PCNA-dependent accumulation of CDKN1A into nuclear foci after ionizing
      irradiation.
AB  - The cyclin-dependent kinase inhibitor CDKN1A/p21 confers cell-cycle arrest in
      response to DNA damage and inhibits DNA replication through its direct
      interaction with the proliferating cell nuclear antigen (PCNA) and cyclin/cyclin
      dependent kinase complexes. Previously, we reported that in response to densely
      ionizing radiation CDKN1A rapidly is recruited to the sites of particle
      traversal, and that CDKN1A foci formation in response to heavy ions is
      independent of its transactivation by TP53. Here, we show that exposure of normal
      human fibroblasts to X-rays or to H2O2 also induces nuclear accumulations of
      CDKN1A. We find that CDKN1A foci formation in response to radiation damage is
      dependent on its dephosphorylation and on its direct physical interaction with
      PCNA. Live cell imaging analyses of ectopically expressed EGFP-CDKN1A and dsRed
      PCNA show rapid recruitment of both proteins into foci after radiation damage.
      Detailed dynamic measurements reveal a slightly delayed recruitment of CDKN1A
      compared to PCNA, which is best described by bi-exponential curve fitting, taking
      the preceding binding of PCNA to DNA into account. We propose a regulatory role
      for CDKN1A in mediating PCNA function after radiation damage, and provide
      evidence that this role is distinct from its involvement in nucleotide excision
      repair and unrelated to double-strand break repair.

PMID- 22456501
TI  - Cardiovascular risk in nonobese hypertensive adolescents: a study based on plasma
      biomarkers and ultrasonographic assessment of early atherosclerosis.
AB  - The objective of this study was to investigate the vascular status, left
      ventricular mass and biomarkers of endothelial activation in hypertensive (HT)
      adolescents, with particular attention to comparing nonobese with obese patients.
      Seventy-nine newly diagnosed HT adolescents aged 15.1+/-2.1 years (divided into
      34 nonobese and 45 obese) were compared with 35 healthy volunteers. Intima-media
      thickness (IMT), flow-mediated dilation (FMD) and left-ventricular mass index
      (LVMi) were determined using ultrasound. Adhesion molecules and inflammatory
      interleukins (ILs), together with lipids and insulin resistance (HOMA), were also
      studied. HT obese adolescents had higher triglycerides, HOMA, and elevated levels
      of interleukin-6, tumor necrosis factor-alpha, soluble intercellular adhesion
      molecule-1 and soluble E-selectin compared with controls and nonobese HT
      patients. FMD was lower in HT groups (8.5+/-4.5% in nonobese, P=0.004; 8.1+/
      4.9%, P=0.01 in obese vs 12.5+/-4.9%; in control), and IMT was higher (0.52+/
      0.06 mm, P<0.001 in nonobese; 0.54+/-0.05 mm, P<0.001 in obese vs 0.42+/-0.05 mm
      in control). Higher LVMi was found in both HT groups, with the highest value in
      the nonobese group being 37.8+/-5.3 g m(-2.7) vs 28.4+/-5.3 g m(-2.7) in controls
      (P=0.003). In conclusion, nonobese HT adolescents had the same early
      cardiovascular deteriorations assessed ultrasonographically as their obese HT
      peers, although metabolic alterations and endothelial activation measured as
      plasma biomarkers were more pronounced in obese individuals. The potential
      mechanisms of early atherosclerosis in nonobese HT adolescents need further
      evaluation in prospective studies because these factors may differ considerably
      from those found in young obese individuals with HT.

PMID- 22456502
TI  - Fetus in feto with spinal dysraphism.

PMID- 22456503
TI  - Postlipolytic insulin-dependent remodeling of micro lipid droplets in adipocytes.
AB  - Despite the lipolysis-lipogenesis cycle being a fundamental process in adipocyte
      biology, very little is known about the morphological changes that occur during
      this process. The remodeling of lipid droplets to form micro lipid droplets
      (mLDs) is a striking feature of lipolysis in adipocytes, but once lipolysis
      ceases, the cell must regain its basal morphology. We characterized mLD formation
      in cultured adipocytes, and in primary adipocytes isolated from mouse epididymal
      fat pads, in response to acute activation of lipolysis. Using real-time
      quantitative imaging and electron tomography, we show that formation of mLDs in
      cultured adipocytes occurs throughout the cell to increase total LD surface area
      by ~30% but does not involve detectable fission from large LDs. Peripheral mLDs
      are monolayered structures with a neutral lipid core and are sites of active
      lipolysis. Electron tomography reveals preferential association of mLDs with the
      endoplasmic reticulum. Treatment with insulin and fatty acids results in the
      reformation of macroLDs and return to the basal state. Insulin-dependent
      reformation of large LDs involves two distinct processes: microtubule-dependent
      homotypic fusion of mLDs and expansion of individual mLDs. We identify a
      physiologically important role for LD fusion that is involved in a reversible
      lipolytic cycle in adipocytes.

PMID- 22456504
TI  - cPLA2alpha and EHD1 interact and regulate the vesiculation of cholesterol-rich,
      GPI-anchored, protein-containing endosomes.
AB  - The lipid modifier phospholipase A2 catalyzes the hydrolysis of phospholipids to
      inverted-cone-shaped lysophospholipids that contribute to membrane curvature
      and/or tubulation. Conflicting findings exist regarding the function of cytosolic
      phospholipase A2 (cPLA2) and its role in membrane regulation at the Golgi and
      early endosomes. However, no studies addressed the role of cPLA2 in the
      regulation of cholesterol-rich membranes that contain
      glycosylphosphatidylinositol-anchored proteins (GPI-APs). Our studies support a
      role for cPLA2alpha in the vesiculation of GPI-AP-containing membranes, using
      endogenous CD59 as a model for GPI-APs. On cPLA2alpha depletion, CD59-containing
      endosomes became hypertubular. Moreover, accumulation of lysophospholipids
      induced by a lysophospholipid acyltransferase inhibitor extensively vesiculated
      CD59-containing endosomes. However, overexpression of cPLA2alpha did not increase
      the endosomal vesiculation, implying a requirement for additional factors.
      Indeed, depletion of the "pinchase" EHD1, a C-terminal Eps15 homology domain
      (EHD) ATPase, also induced hypertubulation of CD59-containing endosomes.
      Furthermore, EHD1 and cPLA2alpha demonstrated in situ proximity (<40 nm) and
      interacted in vivo. The results presented here provide evidence that the lipid
      modifier cPLA2alpha and EHD1 are involved in the vesiculation of CD59-containing
      endosomes. We speculate that cPLA2alpha induces membrane curvature and allows
      EHD1, possibly in the context of a complex, to sever the curved membranes into
      vesicles.

PMID- 22456505
TI  - A conserved cell growth cycle can account for the environmental stress responses
      of divergent eukaryotes.
AB  - The respiratory metabolic cycle in budding yeast (Saccharomyces cerevisiae)
      consists of two phases that are most simply defined phenomenologically: low
      oxygen consumption (LOC) and high oxygen consumption (HOC). Each phase is
      associated with the periodic expression of thousands of genes, producing
      oscillating patterns of gene expression found in synchronized cultures and in
      single cells of slowly growing unsynchronized cultures. Systematic variation in
      the durations of the HOC and LOC phases can account quantitatively for well
      studied transcriptional responses to growth rate differences. Here we show that a
      similar mechanism-transitions from the HOC phase to the LOC phase-can account for
      much of the common environmental stress response (ESR) and for the cross
      protection by a preliminary heat stress (or slow growth rate) to subsequent
      lethal heat stress. Similar to the budding yeast metabolic cycle, we suggest that
      a metabolic cycle, coupled in a similar way to the ESR, in the distantly related
      fission yeast, Schizosaccharomyces pombe, and in humans can explain gene
      expression and respiratory patterns observed in these eukaryotes. Although
      metabolic cycling is associated with the G0/G1 phase of the cell division cycle
      of slowly growing budding yeast, transcriptional cycling was detected in the G2
      phase of the division cycle in fission yeast, consistent with the idea that
      respiratory metabolic cycling occurs during the phases of the cell division cycle
      associated with mass accumulation in these divergent eukaryotes.

PMID- 22456506
TI  - Arp2/3 mediates early endosome dynamics necessary for the maintenance of PAR
      asymmetry in Caenorhabditis elegans.
AB  - The widely conserved Arp2/3 complex regulates branched actin dynamics that are
      necessary for a variety of cellular processes. In Caenorhabditis elegans, the
      actin cytoskeleton has been extensively characterized in its role in establishing
      PAR asymmetry; however, the contributions of actin to the maintenance of polarity
      before the onset of mitosis are less clear. Endocytic recycling has emerged as a
      key mechanism in the dynamic stabilization of cellular polarity, and the large
      GTPase dynamin participates in the stabilization of cortical polarity during
      maintenance phase via endocytosis in C. elegans. Here we show that disruption of
      Arp2/3 function affects the formation and localization of short cortical actin
      filaments and foci, endocytic regulators, and polarity proteins during
      maintenance phase. We detect actin associated with events similar to early
      endosomal fission, movement of endosomes into the cytoplasm, and endosomal
      movement from the cytoplasm to the plasma membrane, suggesting the involvement of
      actin in regulating processes at the early endosome. We also observe aberrant
      accumulations of PAR-6 cytoplasmic puncta near the centrosome along with early
      endosomes. We propose a model in which Arp2/3 affects the efficiency of rapid
      endocytic recycling of polarity cues that ultimately contributes to their stable
      maintenance.

PMID- 22456507
TI  - Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane
      integration, are required for autophagy.
AB  - Autophagy is a catabolic process essential for cell homeostasis, at the core of
      which is the formation of double-membrane organelles called autophagosomes. Atg9
      is the only known transmembrane protein required for autophagy and is proposed to
      deliver membrane to the preautophagosome structures and autophagosomes. We show
      here that mammalian Atg9 (mAtg9) is required for the formation of DFCP1-positive
      autophagosome precursors called phagophores. mAtg9 is recruited to phagophores
      independent of early autophagy proteins, such as ULK1 and WIPI2, but does not
      become a stable component of the autophagosome membrane. In fact, mAtg9-positive
      structures interact dynamically with phagophores and autophagosomes without being
      incorporated into them. The membrane compartment enriched in mAtg9 displays a
      unique sedimentation profile, which is unaltered upon starvation-induced
      autophagy. Correlative light electron microscopy reveals that mAtg9 is present on
      tubular-vesicular membranes emanating from vacuolar structures. We show that
      mAtg9 resides in a unique endosomal-like compartment and on endosomes, including
      recycling endosomes, where it interacts with the transferrin receptor. We propose
      that mAtg9 trafficking through multiple organelles, including recycling
      endosomes, is essential for the initiation and progression of autophagy; however,
      rather than acting as a structural component of the autophagosome, it is required
      for the expansion of the autophagosome precursor.

PMID- 22456508
TI  - Stretch-induced actin remodeling requires targeting of zyxin to stress fibers and
      recruitment of actin regulators.
AB  - Reinforcement of actin stress fibers in response to mechanical stimulation
      depends on a posttranslational mechanism that requires the LIM protein zyxin. The
      C-terminal LIM region of zyxin directs the force-sensitive accumulation of zyxin
      on actin stress fibers. The N-terminal region of zyxin promotes actin
      reinforcement even when Rho kinase is inhibited. The mechanosensitive integrin
      effector p130Cas binds zyxin but is not required for mitogen-activated protein
      kinase-dependent zyxin phosphorylation or stress fiber remodeling in cells
      exposed to uniaxial cyclic stretch. alpha-Actinin and Ena/VASP proteins bind to
      the stress fiber reinforcement domain of zyxin. Mutation of their docking sites
      reveals that zyxin is required for recruitment of both groups of proteins to
      regions of stress fiber remodeling. Zyxin-null cells reconstituted with zyxin
      variants that lack either alpha-actinin or Ena/VASP-binding capacity display
      compromised response to mechanical stimulation. Our findings define a bipartite
      mechanism for stretch-induced actin remodeling that involves mechanosensitive
      targeting of zyxin to actin stress fibers and localized recruitment of actin
      regulatory machinery.

PMID- 22456509
TI  - Endosomal maturation by Rab conversion in Aspergillus nidulans is coupled to
      dynein-mediated basipetal movement.
AB  - We exploit the ease with which highly motile early endosomes are distinguished
      from static late endosomes in order to study Aspergillus nidulans endosomal
      traffic. RabS(Rab7) mediates homotypic fusion of late endosomes/vacuoles in a
      homotypic fusion- and vacuole protein sorting/Vps41-dependent manner. Progression
      across the endocytic pathway involves endosomal maturation because the end
      products of the pathway in the absence of RabS(Rab7) are minivacuoles that are
      competent in multivesicular body sorting and cargo degradation but retain early
      endosomal features, such as the ability to undergo long-distance movement and
      propensity to accumulate in the tip region if dynein function is impaired.
      Without RabS(Rab7), early endosomal Rab5s-RabA and RabB-reach minivacuoles, in
      agreement with the view that Rab7 homologues facilitate the release of Rab5
      homologues from endosomes. RabS(Rab7) is recruited to membranes already at the
      stage of late endosomes still lacking vacuolar morphology, but the transition
      between early and late endosomes is sharp, as only in a minor proportion of
      examples are RabA/RabB and RabS(Rab7) detectable in the same-frequently the less
      motile-structures. This early-to-late endosome/vacuole transition is coupled to
      dynein-dependent movement away from the tip, resembling the periphery-to-center
      traffic of endosomes accompanying mammalian cell endosomal maturation. Genetic
      studies establish that endosomal maturation is essential, whereas homotypic
      vacuolar fusion is not.

PMID- 22456511
TI  - Polo-like kinase 4 controls centriole duplication but does not directly regulate
      cytokinesis.
AB  - Centrioles organize the centrosome, and accurate control of their number is
      critical for the maintenance of genomic integrity. Centrioles duplicate once per
      cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We
      previously demonstrated that Plk4 accumulation is autoregulated by its own kinase
      activity. However, loss of heterozygosity of Plk4 in mouse embryonic fibroblasts
      has been proposed to cause cytokinesis failure as a primary event, leading to
      centrosome amplification and gross chromosomal abnormalities. Using targeted gene
      disruption, we show that human epithelial cells with one inactivated Plk4 allele
      undergo neither cytokinesis failure nor increase in centrosome amplification.
      Plk4 is shown to localize exclusively at the centrosome, with none in the spindle
      midbody. Substantial depletion of Plk4 by small interfering RNA leads to loss of
      centrioles and subsequent spindle defects that lead to a modest increase in the
      rate of cytokinesis failure. Therefore, Plk4 is a centriole-localized kinase that
      does not directly regulate cytokinesis.

PMID- 22456510
TI  - c-Jun N-terminal kinase-mediated Rad18 phosphorylation facilitates Poleta
      recruitment to stalled replication forks.
AB  - The E3 ubiquitin ligase Rad18 chaperones DNA polymerase eta (Poleta) to sites of
      UV-induced DNA damage and monoubiquitinates proliferating cell nuclear antigen
      (PCNA), facilitating engagement of Poleta with stalled replication forks and
      promoting translesion synthesis (TLS). It is unclear how Rad18 activities are
      coordinated with other elements of the DNA damage response. We show here that Ser
      409 residing in the Poleta-binding motif of Rad18 is phosphorylated in a
      checkpoint kinase 1-dependent manner in genotoxin-treated cells. Recombinant
      Rad18 was phosphorylated specifically at S409 by c-Jun N-terminal kinase (JNK) in
      vitro. In UV-treated cells, Rad18 S409 phosphorylation was inhibited by a
      pharmacological JNK inhibitor. Conversely, ectopic expression of JNK and its
      upstream kinase mitogen-activated protein kinase kinase 4 led to DNA damage
      independent Rad18 S409 phosphorylation. These results identify Rad18 as a novel
      JNK substrate. A Rad18 mutant harboring a Ser -> Ala substitution at S409 was
      compromised for Poleta association and did not redistribute Poleta to nuclear
      foci or promote Poleta-PCNA interaction efficiently relative to wild-type Rad18.
      Rad18 S409A also failed to fully complement the UV sensitivity of Rad18-depleted
      cells. Taken together, these results show that Rad18 phosphorylation by JNK
      represents a novel mechanism for promoting TLS and DNA damage tolerance.

PMID- 22456513
TI  - Homogeneous staining regions for cyclin D1, a marker of poor prognosis in
      malignant melanoma.
AB  - Homogeneous staining regions (HSRs) have been previously shown to confer a worse
      prognosis in solid tumors and myelodysplastic syndromes. We previously reported a
      single case of melanoma with HSR for cyclin D1 and postulated that HSR for cyclin
      D1 is an independent poor prognostic indicator. Herein, we report 7 cases of
      melanoma with HSR for cyclin D1. The cases occurred in elderly men and women with
      an average age of 65 years. Three cases occurred in areas of intermittent sun
      exposure, 2 cases occurred in chronically sun-damaged areas, and 2 cases were
      acral. HSR correlated with aggressive histology. The average Breslow depth was
      2.7 mm (range, 1-11 mm), the average mitotic index was 5.1 per square millimeter,
      and 5 of the 7 cases were ulcerated. Clinical follow-up was available for 6 of
      the 7 cases. Five of the 6 cases for which clinical follow-up was available
      metastasized, and 1 patient died of metastatic melanoma. Three cases with
      metastatic disease occurred in primary melanomas with lower Breslow depths,
      ranging from 1.0 to 1.4 mm. These additional cases of melanoma with an aggressive
      clinical course provide further evidence of the prognostic significance of HSR
      for cyclin D1 in melanoma. Larger cohort studies are needed to validate this
      observation.

PMID- 22456512
TI  - Protein kinase C delta regulates the release of collagen type I from vascular
      smooth muscle cells via regulation of Cdc42.
AB  - Collagen type I is the most abundant component of extracellular matrix in the
      arterial wall. Mice knocked out for the protein kinase C delta gene (PKCdelta KO)
      show a marked reduction of collagen I in the arterial wall. The lack of PKCdelta
      diminished the ability of arterial smooth muscle cells (SMCs) to secrete collagen
      I without significantly altering the intracellular collagen content. Moreover,
      the unsecreted collagen I molecules accumulate in large perinuclear puncta. These
      perinuclear structures colocalize with the trans-Golgi network (TGN) marker TGN38
      and to a lesser degree with cis-Golgi marker (GM130) but not with early endosomal
      marker (EEA1). Associated with diminished collagen I secretion, PKCdelta KO SMCs
      exhibit a significant reduction in levels of cell division cycle 42 (Cdc42)
      protein and mRNA. Restoring PKCdelta expression partially rescues Cdc42
      expression and collagen I secretion in PKCdelta KO SMCs. Inhibition of Cdc42
      expression or activity with small interfering RNA or secramine A in PKCdelta WT
      SMCs eliminates collagen I secretion. Conversely, restoring Cdc42 expression in
      PKCdelta KO SMCs enables collagen I secretion. Taken together, our data
      demonstrate that PKCdelta mediates collagen I secretion from SMCs, likely through
      a Cdc42-dependent mechanism.

PMID- 22456514
TI  - Lymph node melanosis from a primary cutaneous lesion combining a nodular
      (tumoral) melanosis and a congenital dermal melanocytic nevus.
AB  - Tumoral or nodular melanosis is considered as a rare manifestation of a
      completely regressed melanoma whose histopathological features include confluent
      dermal nodular aggregates of heavily melanized polygonal cells consistent with
      melanophages. Tumoral melanosis involving also lymph node is an even rarer event
      that has been reported only twice in the literature. We report a case of lymph
      node melanosis in the sentinel lymph node draining from a primary cutaneous
      lesion combining a dermal tumoral melanosis consistent with a complete regressed
      melanoma associated with a residual part of a deep congenital nevus. We discuss
      the histopathological diagnosis of our primary cutaneous lesion and the sentinel
      lymph node microscopic findings, compare our case with the previous ones, and
      discuss the possible prognostic and therapeutic implications.

PMID- 22456515
TI  - Neurofibroma-like spindle cell melanoma: CD34 fingerprint and CGH for diagnosis.
AB  - We present a case that highlights the use of two maneuvers useful in the
      diagnosis of spindle cell melanoma. A shave biopsy from the cheek of a 58-year
      old man demonstrated a thin invasive melanoma of 0.3 mm thickness with a less
      than 2-mm-wide intra-epidermal component. Below this melanocytic lesion, but not
      contiguous with it, there was a transected S-100-positive and Melan-A-negative
      spindle cell proliferation. Upon re-excision, no residuum of conventional
      melanoma was identified, but a residual spindle cell neoplasm that was 4 mm in
      diameter, nodular, well-circumscribed, cytologically bland, and S-100 positive
      was noted. At our consensus conference, our group favored neurofibroma but agreed
      that spindle cell melanoma could not be excluded based on histopathologic
      features alone. To further address the differential diagnosis, we performed CD34
      staining that demonstrated lack of a CD34 fingerprint. We also completed array
      based comparative genomic hybridization, which demonstrated gain of chromosome
      6p, loss of 6p and gain of 7. These two methods of analysis support a diagnosis
      of spindle cell melanoma.

PMID- 22456516
TI  - Oral lesions in leprosy revisited:  a case report.
AB  - There is a scarcity of the histopathologically proven lesions of leprosy in the
      oral cavity, in the world literature. A 55-year-old man had come with a complaint
      of asymptomatic nodular lesions in the oral cavity. Cutaneous lesions and
      peripheral nerve examination were suggestive of lepromatous leprosy.
      Histopathologic examination of a nodule on the palate demonstrated diffuse
      macrophagic granulomas and acid-fast bacilli.

PMID- 22456517
TI  - Broken livedo:  clue to a systemic disease.

PMID- 22456518
TI  - Expression of lysozymes from Erwinia amylovora phages and Erwinia genomes and
      inhibition by a bacterial protein.
AB  - Genes coding for lysozyme-inhibiting proteins (Ivy) were cloned from the
      chromosomes of the plant pathogens Erwinia amylovora and Erwinia pyrifoliae. The
      product interfered not only with activity of hen egg white lysozyme, but also
      with an enzyme from E. amylovora phage PhiEa1h. We have expressed lysozyme genes
      from the genomes of three Erwinia species in Escherichia coli. The lysozymes
      expressed from genes of the E. amylovora phages PhiEa104 and PhiEa116, Erwinia
      chromosomes and Arabidopsis thaliana were not affected by Ivy. The enzyme from
      bacteriophage PhiEa1h was fused at the N- or C-terminus to other peptides.
      Compared to the intact lysozyme, a His-tag reduced its lytic activity about 10
      fold and larger fusion proteins abolished activity completely. Specific protease
      cleavage restored lysozyme activity of a GST-fusion. The bacteriophage-encoded
      lysozymes were more active than the enzymes from bacterial chromosomes. Viral lyz
      genes were inserted into a broad-host range vector, and transfer to E. amylovora
      inhibited cell growth. Inserted in the yeast Pichia pastoris, the PhiEa1h
      lysozyme was secreted and also inhibited by Ivy. Here we describe expression of
      unrelated cloned 'silent' lyz genes from Erwinia chromosomes and a novel
      interference of bacterial Ivy proteins with a viral lysozyme.

PMID- 22456519
TI  - Basic science for the clinician 55: CTLA-4.
AB  - In physiological systems, for every "yang," there must be a "yin," for
      uncontrolled systems can run amok. This is the case for the T-cell compartment of
      the immune system, where activation must be modulated, dampened, and ultimately
      reversed; to not apply the brakes leads to dire consequences. In less than 20
      years, CTLA-4 has emerged from being an orphan, next becoming a physiological
      star with ever-emerging effects, and finally to being a therapeutic target-an
      impressive example of evolution and one that continues. Understanding the
      costimulatory effects and mechanisms of CTLA-4 and the redundancies intrinsic to
      costimulation is important in understanding T-cell function and dysfunction in
      disease. A future article in this series will describe inducible T-cell
      costimulator, which is a normal by-pass to CTLA-4's effects.

PMID- 22456520
TI  - "Renal rim sign": a diagnostic radiological sign of IgG4-related
      tubulointerstitial nephritis?

PMID- 22456521
TI  - Bone changes in a patient with tuberous sclerosis complex.

PMID- 22456522
TI  - An unusual presentation of acute calcium pyrophosphate dihydrate arthropathy of
      the sternoclavicular joint in a patient with systemic lupus erythematosus.

PMID- 22456524
TI  - Rapid, progressive tumoral calcinosis mimicking treatment-resistant rheumatoid
      arthritis.

PMID- 22456525
TI  - Construction of multi-component supramolecular architectures of bile acids and
      cinchona alkaloids through helical-pitch-synchronized crystallization.
AB  - Molecular assemblies based on helical motifs are of substantial interest from the
      view point of fundamental science as well as application. In this study, we
      propose a new class of organic crystal, that is, heteroH-MOC (multi-component
      organic crystal containing different kinds of helical motifs consisted of
      different components), and describe successful construction of heteroH-MOCs with
      P2(1) and P2(1)2(1)2(1) space groups by using steroidal bile acids and cinchona
      alkaloids. In the P2(1) crystals, two kinds of helices composed of the steroid
      and alkaloid are arranged in a parallel fashion, while, in the P2(1)2(1)2(1)
      crystals, those are in a perpendicular fashion. It is remarkable that, in such
      systems, particularly in the latter crystals, components ingeniously achieved
      highly-ordered synchronization of periodicity (helical pitches r and periodic
      distances in the array of helices p), which is first demonstrated in this study
      through hierarchical interpretation of the crystal structures.

PMID- 22456526
TI  - Prognostic significance of MCM7 expression in the bronchial brushings of patients
      with non-small cell lung cancer (NSCLC).
AB  - PURPOSE: To identify potential biomarkers for the prognosis of non-small cell
      lung cancer (NSCLC) patients by using bronchial brushing specimens. METHODS: The
      expression of MCM7, Ki67 and EGFR was evaluated in 494 NSCLC tissues and 174
      bronchial brushings using immunohistochemical and immunocytochemical techniques.
      Associations between protein expression and clinico-pathologic parameters were
      assessed, and the impact on overall survival (OS) was analyzed. RESULTS: High
      expression of MCM7, Ki67 and EGFR was detected in 33.3%, 23.5% and 12.7% of
      tissues and in 52.4%, 52.7% and 20.6% of bronchial brushings, respectively.
      Expression of MCM7 and Ki67 was associated with squamous cell carcinoma (SCC) in
      both tissues and bronchial brushings (MCM7: P = 0.0007, 0.00003; Ki67: P <
      0.00001, 0.00001). Overexpression of MCM7 in tumor tissues was detected more
      frequently in poorly differentiated tumors (P = 0.0120) and non
      bronchioloalveolar carcinomas (non-BACs) (P = 0.0238). EGFR overexpression was
      observed in tissues of larger tumors (P = 0.00004) and in bronchial brushings at
      later stage (P = 0.0262). Kaplan-Meier curves indicated that patients with
      overexpression of MCM7 or Ki67 had a poorer OS compared to those with low
      expression for all stages (P < 0.00001, 0.0233) and early-stages (P < 0.00001,
      0.0032). In particular, the patients with MCM7 overexpression in bronchial
      brushings had a poorer prognosis (P = 0.0045). Multivariate Cox regression
      analysis showed that MCM7 was an independent prognostic indicator both in tissue
      samples and bronchial brushings. CONCLUSIONS: Our data suggest that MCM7 and Ki67
      in tumor tissues may be potential markers of a poor prognosis for NSCLC patients.
      MCM7 in bronchial brushings also showed an independent prognostic value, which
      may be useful when biopsies are unavailable.

PMID- 22456527
TI  - Granulocyte colony-stimulating factor improves cerebrovascular reserve capacity
      by enhancing collateral growth in the circle of Willis.
AB  - BACKGROUND AND PURPOSE: Restoration of cerebrovascular reserve capacity (CVRC)
      depends on the recruitment and positive outward remodeling of preexistent
      collaterals (arteriogenesis). With this study, we provide functional evidence
      that granulocyte colony-stimulating factor (G-CSF) augments therapeutic
      arteriogenesis in two animal models of cerebral hypoperfusion. We identified an
      effective dosing regimen that improved CVRC and stimulated collateral growth,
      thereby improving the outcome after experimentally induced stroke. METHODS: We
      used two established animal models of (a) cerebral hypoperfusion (mouse, common
      carotid artery ligation) and (b) cerebral arteriogenesis (rat, 3-vessel
      occlusion). Following therapeutic dose determination, both models received either
      G-CSF, 40 MUg/kg every other day, or vehicle for 1 week. Collateral vessel
      diameters were measured following latex angiography. Cerebrovascular reserve
      capacities were assessed after acetazolamide stimulation. Mice with left common
      carotid artery occlusion (CCAO) were additionally subjected to middle cerebral
      artery occlusion, and stroke volumes were assessed after triphenyltetrazolium
      chloride staining. Given the vital role of monocytes in arteriogenesis, we
      assessed (a) the influence of G-CSF on monocyte migration in vitro and (b)
      monocyte counts in the adventitial tissues of the growing collaterals in vivo.
      RESULTS: CVRC was impaired in both animal models 1 week after induction of
      hypoperfusion. While G-CSF, 40 MUg/kg every other day, significantly augmented
      cerebral arteriogenesis in the rat model, 50 or 150 MUg/kg every day did not show
      any noticeable therapeutic impact. G-CSF restored CVRC in mice (5 +/- 2 to 12 +/-
      6%) and rats (3 +/- 4 to 19 +/- 12%). Vessel diameters changed accordingly: in
      rats, the diameters of posterior cerebral arteries (ipsilateral: 209 +/- 7-271 +/
      57 MUm; contralateral: 208 +/- 11-252 +/- 28 MUm) and in mice the diameter of
      anterior cerebral arteries (185 +/- 15-222 +/- 12 MUm) significantly increased in
      the G-CSF groups compared to controls. Stroke volume in mice (10 +/- 2%) was
      diminished following CCAO (7 +/- 4%) and G-CSF treatment (4 +/- 2%). G-CSF
      significantly increased monocyte migration in vitro and perivascular monocyte
      numbers in vivo. CONCLUSION: G-CSF augments cerebral collateral artery growth,
      increases CVRC and protects from experimentally induced ischemic stroke. When
      comparing three different dosing regimens, a relatively low dosage of G-CSF was
      most effective, indicating that the common side effects of this cytokine might be
      significantly reduced or possibly even avoided in this indication.

PMID- 22456528
TI  - Comparison of two methods for the management of intraoperative hypothermia in
      dogs.

PMID- 22456529
TI  - Use of a circular fixator construct for metacarpal fracture stabilisation in a
      fawn.

PMID- 22456530
TI  - The hepatic soluble guanylyl cyclase-cyclic guanosine monophosphate pathway
      mediates the protection of remote ischemic preconditioning on the
      microcirculation in liver ischemia-reperfusion injury.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) protects against liver
      ischemia reperfusion (IR) injury. An essential circulating mediator of this
      protection is nitric oxide (NO) induced by lower limb RIPC. One of the mechanisms
      through which NO generally acts is the soluble guanylyl cyclase-cyclic GMP (sGC
      cGMP) pathway. The present study aimed to assess the role of hepatic sGC-cGMP in
      lower limb RIPC-induced protection against liver IR injury. METHODS: Mice were
      allocated to 4 groups: 1.Sham; 2.IR: 40 min of lobar hepatic ischemia and 2 hr
      reperfusion; 3.RIPC+IR: 6 cycles of 4x4 min IR of the lower limb followed by IR
      group procedure; (4) 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ)+RIPC+IR:
      ODQ (sGC inhibitor) was administered followed by RIPC+IR group procedure. Hepatic
      microcirculatory blood flow (MBF) was measured throughout the experiment. Plasma
      transaminases, hepatic histopathological and transmission electron microscopy
      studies were performed at the end of the experiment. Hepatic cGMP levels were
      measured in groups 1-3 in addition to an RIPC alone group. RESULTS: Compared to
      liver IR alone, RIPC+IR increased hepatic MBF during liver reperfusion (P<0.05),
      and reduced plasma transaminases (P<0.05) and ultrastructural markers of injury.
      In contrast compared to RIPC+IR, ODQ+RIPC+IR decreased hepatic MBF (P<0.05) and
      ultrastructural markers of injury. However, plasma transaminases were not
      significantly different in the ODQ+RIPC+IR compared to the RIPC+IR group. Hepatic
      cGMP levels were significantly elevated in the RIPC compared to sham group.
      CONCLUSIONS: The hepatic sGC-cGMP pathway is required for mediating the
      protective effects of lower limb RIPC on hepatic MBF in liver IR injury.

PMID- 22456531
TI  - Tuning metal hydride thermodynamics via size and composition: Li-H, Mg-H, Al-H,
      and Mg-Al-H nanoclusters for hydrogen storage.
AB  - Nanoscale Li and intermetallic Al-Mg metal hydride clusters are investigated as a
      possible hydrogen storage material using the high-level quantum Monte Carlo
      computational method. Lower level methods such as density functional theory are
      qualitatively, not quantitatively accurate for the calculation of the enthalpy of
      absorption of H(2). At sizes around 1 nm, it is predicted that Al/Mg alloyed
      nanoparticles are stable relative to the pure compositions and the metal
      composition can be tuned in tandem with the size to tune the hydrogen absorption
      energy, making this a promising route to a rechargeable hydrogen storage
      material.

PMID- 22456532
TI  - Pressure and temperature dependence of the decomposition pathway of LiBH4.
AB  - The decomposition pathway is crucial for the applicability of LiBH(4) as a
      hydrogen storage material. We discuss and compare the different decomposition
      pathways of LiBH(4) according to the thermodynamic parameters and show the
      experimental ways to realize them. Two pathways, i.e. the direct decomposition
      into boron and the decomposition via Li(2)B(12)H(12), were realized under
      appropriate conditions, respectively. By applying a H(2) pressure of 50 bar at
      873 K or 10 bar at 700 K, LiBH(4) is forced to decompose into Li(2)B(12)H(12). In
      a lower pressure range of 0.1 to 10 bar at 873 K and 800 K, the concurrence of
      both decomposition pathways is observed. Raman spectroscopy and (11)B MAS NMR
      measurements confirm the formation of an intermediate Li(2)B(12)H(12) phase
      (mostly Li(2)B(12)H(12) adducts, such as dimers or trimers) and amorphous boron.

PMID- 22456533
TI  - Keggin polyanion and copper cluster based coordination polymer towards model for
      complex nanosystem.
AB  - Synthesis and tuning the structure of metal-organic nanoclusters in coordination
      polymer by different charged polyanions ([PMo(12)O(40)](3-) and [SiMo(12)O(40)](4
      )).

PMID- 22456534
TI  - Analysis of fatty acid composition in insulin secreting cells by comprehensive
      two-dimensional gas chromatography time-of-flight mass spectrometry.
AB  - A comprehensive two-dimensional gas chromatography (GC*GC) time-of-flight mass
      spectrometry method was developed for determination of fatty acids (irrespective
      of origin, i.e., both free fatty acids and fatty acids bound in sources such as
      triglycerides) in cultured mammalian cells. The method was applied to INS-1
      cells, an insulin-secreting cell line commonly used as a model in diabetes
      studies. In the method, lipids were extracted and transformed to fatty acid
      methyl esters for analysis. GC*GC analysis revealed the presence of 30
      identifiable fatty acids in the extract. This result doubles the number of fatty
      acids previously identified in these cells. The method yielded linear
      calibrations and an average relative standard deviation of 8.4% for replicate
      injections of samples and 12.4% for replicate analysis of different samples. The
      method was used to demonstrate changes in fatty acid content as a function of
      glucose concentration on the cells. These results demonstrate the utility of this
      method for analysis of fatty acids in mammalian cell cultures.

PMID- 22456535
TI  - Validation of the PCR-dHPLC method for rapid identification of Candida glabrata
      phylogenetically related species in different biological matrices.
AB  - Since two new species phylogenetically related to Candida glabrata with slightly
      different phenotypes and antifungal susceptibility profiles have been described,
      it seems to be necessary from clinical point of view, to develop a rapid and
      accurate identification system in order to distinguish between these three fungal
      species. We studied the performance of denaturing high performance liquid
      chromatography (dHPLC) as a faster (less than 7 min) and alternative novel
      technique for simultaneous analysis of Candida species in different biological
      matrices. The analyses show the good low limit of detection (LLOD) in all
      biological matrices studied (5.16-9.56 ngMUL(-1), 4.14-4.70 ng MUL(-1) and 3.99
      4.66 ng MUL(-1) for Candida bracarensis, Candida nivariensis and C. glabrata,
      respectively). 180 Candida isolates were analyzed in order to demonstrate the
      method suitability for screening analysis to identify C. glabrata and its cryptic
      species (C. bracarensis and C. nivariensis) in clinical routine.

PMID- 22456537
TI  - Differential impact of REM sleep deprivation on cytoskeletal proteins of brain
      regions involved in sleep regulation.
AB  - Rapid eye movement (REM) sleep is involved in memory consolidation, which implies
      synaptic plasticity. This process requires protein synthesis and the
      reorganization of the neural cytoskeleton. REM sleep deprivation (REMSD) has an
      impact on some neuronal proteins involved in synaptic plasticity, such as
      glutamate receptors and postsynaptic density protein 95, but its effects on
      cytoskeletal proteins is unknown. In this study, the effects of REMSD on the
      content of the cytoskeletal proteins MAP2 and TAU were analyzed. Adult female
      rats were submitted to selective REMSD by using the multiple platform technique.
      After 24, 48 or 72 h of REMSD, rats were decapitated and the following brain
      areas were dissected: pons, preoptic area, hippocampus and frontal cortex.
      Protein extraction and Western blot were performed. Results showed an increase in
      TAU content in the pons, preoptic area and hippocampus after 24 h of REMSD, while
      in the frontal cortex a significant increase in TAU content was observed after 72
      h of REMSD. A TAU content decrease was observed in the hippocampus after 48 h of
      REMSD. Interestingly, a marked increase in TAU content was observed after 72 h of
      REMSD. MAP2 content only increased in the preoptic area at 24 h, and in the
      frontal cortex after 24 and 72 h of REMSD, without significant changes in the
      pons and hippocampus. These results support the idea that REM sleep plays an
      important role in the organization of neural cytoskeleton, and that this effect
      is tissue-specific.

PMID- 22456536
TI  - Neighborhood built environment and transport and leisure physical activity:
      findings using objective exposure and outcome measures in New Zealand.
AB  - BACKGROUND: Evidence of associations between neighborhood built environments and
      transport-related physical activity (PA) is accumulating, but few studies have
      investigated associations with leisure-time PA. OBJECTIVE: We investigated
      associations of five objectively measured characteristics of the neighborhood
      built environment-destination access, street connectivity, dwelling density, land
      use mix and streetscape quality-with residents' self-reported PA (transport,
      leisure, and walking) and accelerometer-derived measures of PA. METHODS: Using a
      multicity stratified cluster sampling design, we conducted a cross-sectional
      survey of 2,033 adults who lived in 48 New Zealand neighborhoods. Multilevel
      regression modeling, which was adjusted for individual-level (sociodemographic
      and neighborhood preference) and neighborhood-level (deprivation) confounders,
      was used to estimate associations of built environment with PA. RESULTS: We found
      that 1-SD increases in destination access, street connectivity, and dwelling
      density were associated with any versus no self-reported transport, leisure, or
      walking PA, with increased odds ranging from 21% [street connectivity with
      leisure PA, 95% confidence interval (CI): 0%, 47%] to 44% (destination
      accessibility with walking, 95% CI: 17%, 79%). Among participants who self
      reported some PA, a 1-SD increase in street connectivity was associated with a
      13% increase in leisure PA (95% CI: 0, 28%). SD increases in destination access,
      street connectivity, and dwelling density were each associated with 7% increases
      in accelerometer counts. CONCLUSIONS: Associations of neighborhood destination
      access, street connectivity, and dwelling density with self-reported and
      objectively measured PA were moderately strong, indicating the potential to
      increase PA through changes in neighborhood characteristics.

PMID- 22456538
TI  - Bioinspired steel surfaces with extreme wettability contrast.
AB  - The exterior structures of natural organisms have continuously evolved by
      controlling wettability, such as the Namib Desert beetle, whose back has
      hydrophilic/hydrophobic contrast for water harvesting by mist condensation in dry
      desert environments, and some plant leaves that have hierarchical
      micro/nanostructures to collect or repel liquid water. In this work, we have
      provided a method for wettability contrast on alloy steels by both nano-flake or
      needle patterns and tuning of the surface energy. Steels were provided with
      hierarchical micro/nanostructures of Fe oxides by fluorination and by a
      subsequent catalytic reaction of fluorine ions on the steel surfaces in water. A
      hydrophobic material was deposited on the structured surfaces, rendering
      superhydrophobicity. Plasma oxidization induces the formation of superhydrophilic
      surfaces on selective regions surrounded by superhydrophobic surfaces. We show
      that wettability contrast surfaces align liquid water within patterned
      hydrophilic regions during the condensation process. Furthermore, this method
      could have a greater potential to align other liquids or living cells.

PMID- 22456539
TI  - Gottron's papules exhibit dermal accumulation of CD44 variant 7 (CD44v7) and its
      binding partner osteopontin: a unique molecular signature.
AB  - The accumulated mucin in non-Gottron's dermatomyositis (DM) lesions is primarily
      chondroitin-4-sulfate (C4S), which is immunomodulatory in vitro. Gottron's
      papules are a particularly resistant manifestation of DM that often persist after
      other lesions have resolved with therapy. We examined non-Gottron's DM lesions
      and Gottron's papule skin biopsies for C4S, CD44 variant 7 (CD44v7), a
      chondroitin sulfate-binding isoform causally implicated in autoimmunity, and
      osteopontin (OPN), a CD44v7 ligand implicated in chronic inflammation. Gottron's
      papule dermis contained more C4S and CD44v7 than non-Gottron's lesions. Normal
      skin showed less CD44v7 over joints relative to Gottron's lesions. All DM dermis
      had increased OPN compared with healthy skin. Mechanically stretching cultured
      fibroblasts for 6 hours induced CD44v7 mRNA and protein, whereas IFN-gamma
      treatment induced OPN mRNA and protein. OPN alone did not induce CD44v7, but
      stretching dermal fibroblasts in the presence of OPN increased human acute
      monocytic leukemia cell line (THP-1) monocyte binding, which is blunted by anti
      CD44v7 blocking antibody. C4S, CD44v7, and OPN are three molecules uniquely
      present in Gottron's papules that contribute to inflammation individually and in
      association with one another. We propose that stretch-induced CD44v7 over joints,
      in concert with dysregulated OPN levels in the skin of DM patients, increases
      local inflammatory cell recruitment and contributes to the pathogenesis and
      resistance of Gottron's papules.

PMID- 22456540
TI  - Genetic barrier to the development of resistance to integrase inhibitors in HIV-1
      subtypes CRF01_AE and B.
AB  - OBJECTIVE: The genetic barrier for the evolution of integrase inhibitors (INIs)
      including raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG)
      resistance was compared between HIV-1 subtypes CRF01_AE and B. METHODS: Analysis
      of 66 substitutions associated with INI resistance at 41 amino acid positions in
      144 nucleotide sequences (109 HIV-1 subtype CRF01_AE and 35 HIV-1 subtype B) of
      integrase-coding region of polymerase gene derived from INI-naive patients.
      RESULTS: 28/41 studied amino acid positions were conserved, leading to a similar
      genetic barrier between the two subtypes. At six codon positions with different
      genetic barriers, six mutations (V72I, L101I, A124T, T125K, and G140C/S)
      displayed a higher genetic barrier and one mutation (V201I) showed a lower
      genetic barrier in subtype CRF01_AE than subtype B. CONCLUSIONS: Most studied
      amino acid positions including all corresponding to RAL and EVG primary mutations
      show a high level of conservation, indicating the same genetic barrier between
      subtypes CRF01_AE and B. Nevertheless, different genetic barriers were observed
      in two mutations described to be associated with DTG resistance (L101I, A124T)
      and other five RAL and EVG secondary mutations (V72I, T125K, G140C/S, V201I),
      which could have an impact on the development of resistance to RAL, EVG, and DTG.

PMID- 22456542
TI  - 1D 13C-NMR data as molecular descriptors in spectra--structure relationship
      analysis of oligosaccharides.
AB  - Spectra-structure relationships were investigated for estimating the anomeric
      configuration, residues and type of linkages of linear and branched
      trisaccharides using 13C-NMR chemical shifts. For this study, 119 pyranosyl
      trisaccharides were used that are trimers of the alpha or beta anomers of D
      glucose, D-galactose, D-mannose, L-fucose or L-rhamnose residues bonded through a
      or b glycosidic linkages of types 1->2, 1->3, 1->4, or 1->6, as well as
      methoxylated and/or N-acetylated amino trisaccharides. Machine learning
      experiments were performed for: (1) classification of the anomeric configuration
      of the first unit, second unit and reducing end; (2) classification of the type
      of first and second linkages; (3) classification of the three residues: reducing
      end, middle and first residue; and (4) classification of the chain type. Our
      previously model for predicting the structure of disaccharides was incorporated
      in this new model with an improvement of the predictive power. The best results
      were achieved using Random Forests with 204 di- and trisaccharides for the
      training set-it could correctly classify 83%, 90%, 88%, 85%, 85%, 75%, 79%, 68%
      and 94% of the test set (69 compounds) for the nine tasks, respectively, on the
      basis of unassigned chemical shifts.

PMID- 22456541
TI  - Metabolic syndrome is linked to chromosome 7q21 and associated with genetic
      variants in CD36 and GNAT3 in Mexican Americans.
AB  - The prevalence of metabolic syndrome (MS) has been rising alarmingly worldwide,
      including in the United States, but knowledge on specific genetic determinants of
      MS is very limited. Therefore, we planned to identify the genetic determinants of
      MS as defined by National Cholesterol Education Program/Adult Treatment Panel III
      (NCEP/ATPIII) criteria. We performed linkage screen for MS using data from 692
      Mexican Americans, who participated in the San Antonio Family
      Diabetes/Gallbladder Study (SAFDGS). We found strong evidence for linkage of MS
      on chromosome 7q (LOD = 3.6, empirical P = 6.0 * 10(-5)), between markers D7S2212
      and D7S821. In addition, six chromosomal regions exhibited potential evidence for
      linkage (LOD >=1.2) with MS. Furthermore, we examined 29 single-nucleotide
      polymorphisms (SNPs) from the fatty acid translocase (FAT or CD36, 18 SNPs) gene
      and guanine nucleotide binding protein, alpha transducing 3 (GNAT3, 11 SNPs)
      gene, located within the 1-LOD support interval region for their association with
      MS and its related traits. Several SNPs were associated with MS and its related
      traits. Remarkably, rs11760281 in GNAT3 and rs1194197 near CD36 exhibited the
      strongest associations with MS (P = 0.0003, relative risk (RR) = 1.6 and P =
      0.004, RR = 1.7, respectively) and several other related traits. These two
      variants explained ~18% of the MS linkage evidence on chromosome 7q21, and
      together conferred approximately threefold increase in MS risk (RR = 2.7). In
      conclusion, our linkage and subsequent association studies implicate a region on
      chromosome 7q21 to influence MS in Mexican Americans.

PMID- 22456543
TI  - Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects
      in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of
      toxicity using non-tumor cells.
AB  - Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N
      Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate
      with different bromonitrobenzenes, followed by reduction of the nitro groups of
      the coupling products to the corresponding amino compounds. The
      aminodi(hetero)arylamines thus obtained were evaluated for their growth
      inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma),
      A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG(2)
      (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated
      using a porcine liver primary cell culture (PLP1), established by us. The
      aminodi(hetero)arylamine with the NH(2) group in the ortho position and an OMe
      group in the para position to the NH of the di(hetero)arylamine, is the most
      promising compound giving the lowest GI(50) values (1.30-1.63 uM) in all the
      tested human tumor cell lines, presenting no toxicity to PLP1 at those
      concentrations. The effect of this compound on the cell cycle and induction of
      apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered
      the cell cycle profile causing a decrease in the percentage of cells in the G0/G1
      phase and an increase of the apoptosis levels.

PMID- 22456544
TI  - HPAI 9G DNAChip: discrimination of highly pathogenic influenza virus genes.
AB  - The HPAI 9G DNAChip discriminates the single nucleotide polymorphism of H5N1,
      H5N1 (K), and H5N3 in a 60:1 ratio. It allows the simultaneous detection of
      highly pathogenic avian influenza viruses with a signal to background ratio of
      200 and 100% target-specific hybridization in 30 min at 25  degrees C.

PMID- 22456545
TI  - Improving the experiences of people with disabilities.

PMID- 22456548
TI  - Don't forget the family.

PMID- 22456549
TI  - Emphasis on breastfeeding.

PMID- 22456550
TI  - Emphasis on breastfeeding.

PMID- 22456551
TI  - Emphasis on breastfeeding.

PMID- 22456552
TI  - Nursing behind bars.

PMID- 22456553
TI  - Stretching the time between bone density screenings.

PMID- 22456554
TI  - Nurse-led teams in chronic disease management.

PMID- 22456556
TI  - Hospital noise puts patients at risk.

PMID- 22456558
TI  - Abortion rate stays flat worldwide, but unsafe abortion rates climb.

PMID- 22456560
TI  - Elective early births put moms and infants at risk.

PMID- 22456561
TI  - The ACA and the undocumented.
AB  - With shrinking charity care subsidies, who will care for those excluded from
      health care reform's benefits?

PMID- 22456563
TI  - New indication for HIV drug.

PMID- 22456565
TI  - Hard lessons from a long hospital stay.
AB  - This narrative is related in the alternating voices of the two authors. One
      author, a 55-year-old man, quadriplegic from primary progressive multiple
      sclerosis, describes the 10 weeks he spent in four facilities for treatment of a
      stage IV ischial pressure ulcer. The other author, his friend and health care
      proxy, describes the advocacy and personal assistance she gave him in the face of
      often inadequate care that at times threatened his safety, comfort, and emotional
      well-being. The authors describe their differing perspectives on this care, which
      involved a transfer onto his open wound, frequently missed meals, and poor bowel
      management and personal hygiene. They believe that inadequate staffing and
      insufficient training and supervision of nursing assistants, among other factors,
      underlay these problems.

PMID- 22456569
TI  - Are you 'PPD positive'?

PMID- 22456570
TI  - Cancer-related fatigue.

PMID- 22456575
TI  - Cultivating quality:  early postoperative ambulation:  back to basics.

PMID- 22456576
TI  - Giving up--or not?

PMID- 22456577
TI  - Cerebral microbleeds and long-term cognitive outcome: longitudinal cohort study
      of stroke clinic patients.
AB  - BACKGROUND: Vascular cognitive impairment causes significant disability in the
      elderly and is common following ischaemic stroke. Although the underlying
      mechanisms and prognostic factors remain unclear, small vessel diseases are known
      to contribute. Cerebral microbleeds (CMBs) are a magnetic resonance imaging (MRI)
      manifestation of small vessel diseases and may contribute to vascular cognitive
      impairment, particularly frontal-executive functions. We hypothesized that
      baseline CMBs would predict long-term cognitive outcome, specifically frontal
      executive function. METHODS: A cohort of consecutive patients found to have CMBs
      when first referred to a stroke clinic, together with a CMB-free control group
      matched for age, gender and clinicoradiological characteristics, were invited for
      follow-up cognitive assessment a median of 5.7 years later. MRI and detailed
      cognitive assessment (including current intellectual function, verbal memory,
      visual memory, naming skills, perceptual functions, frontal-executive functions;
      and speed and attention) were performed at baseline and follow-up. Patients were
      classified (blinded to MRI and clinical data) as impaired or unimpaired in each
      domain using predefined criteria. We compared the prevalence of cognitive
      impairments in each domain at baseline and follow-up and investigated clinical
      and radiological predictors [including baseline CMBs and white matter changes
      (WMCs)] of frontal-executive cognitive impairment. RESULTS: Of the original
      cohort of 55 patients, 13 died without follow-up. Twenty-six of the surviving
      patients (9 with, 17 without baseline CMBs) agreed to follow-up
      neuropsychological assessment; 21 of these patients had a repeat MRI scan. The
      median number of cognitive domains impaired increased, regardless of the presence
      of baseline CMBs (with baseline CMBs: median 3, range 0-5 at follow-up vs. median
      2, range 0-2 at baseline, p = 0.016; without CMBs: median 1.0, range 0-5 at
      follow-up vs. median 0, range 0-5 at baseline, p = 0.035). Frontal-executive
      impairment at follow-up was more prevalent in patients with baseline CMBs than in
      those without (78 vs. 29%, p = 0.038). The presence of baseline CMBs predicted
      frontal-executive impairment at follow-up (OR 8.40, 95% CI 1.27-55.39, p =
      0.027). Fifty percent of patients with CMBs versus 8% of patients without
      baseline CMBs developed new CMBs (p = 0.047). The severity of WMCs increased; the
      difference was statistically significant only in patients without baseline CMBs
      (p = 0.027). There were no new cortical infarcts. CONCLUSION: In stroke clinic
      patients, CMBs are consistently associated with frontal-executive impairment;
      baseline CMBs are associated with frontal-executive impairment at follow-up after
      5.7 years. The presence of CMBs has prognostic relevance for long-term cognitive
      outcome in stroke clinic patients, and may help to optimally target preventive
      strategies in individuals at highest risk of cognitive decline.

PMID- 22456579
TI  - A didactic note on alcoholism. 1943.

PMID- 22456580
TI  - Commentary on 'A didactic note on alcoholism'.

PMID- 22456581
TI  - Development of personal narratives as a mediator of the impact of deficits in
      social cognition and social withdrawal on negative symptoms in schizophrenia.
AB  - Although negative symptoms are a barrier to recovery from schizophrenia, little
      is understood about the psychological processes that reinforce and sustain them.
      To explore this issue, this study used structural equation modeling to test
      whether the impact of social withdrawal and emotion recognition deficits upon
      negative symptoms is mediated by the richness or poverty of personal narratives.
      The participants were 99 adults with schizophrenia spectrum disorders. Social
      cognition was assessed using the Bell-Lysaker Emotional Recognition Task; social
      withdrawal, using the Quality of Life Scale; narrative coherence, using the Scale
      To Assess Narrative Development; and negative symptoms, using the Positive and
      Negative Syndrome Scale. The findings reveal that although social cognition
      deficits and social withdrawal are significantly associated with negative symptom
      severity, these relationships become nonsignificant when personal narrative
      integrity is examined as a mediating factor. These results indicate that the
      development of personal narratives may be directly linked to the severity of
      negative symptoms; this construct may be a useful target for future
      interventions.

PMID- 22456582
TI  - Patterns of autobiographical memory in bipolar disorder examined by psychometric
      and functional neuroimaging methods.
AB  - This is the first study to combine psychometric and functional neuroimaging
      methods to study altered patterns of autobiographical memory in bipolar disorder
      (BD). All participants were interviewed with an expanded version of the
      Bielefelder Autobiographical Memory Inventory (Bielefelder Autobiographisches
      Gedachtnis Inventar 2004;Lisse: Swets and Zeitlinger). We then acquired
      functional magnetic resonance imaging data during a task of individually designed
      autobiographical recall. Compared with healthy controls, BD patients reported a
      stronger emotionality of autobiographical memories and more frequent
      recollections of autobiographical events during their everyday life. Furthermore,
      they failed to deactivate areas in the cuneus and lingual gyrus and showed
      decreased activation in the inferior frontal and precentral areas compared with
      the control group. More frequent intrusions from a person's past, which had a
      neural correlate in the lack of deactivation in some default mode network areas
      in BD patients, may contribute to manic or depressive symptoms.

PMID- 22456583
TI  - Not only body weight perception but also body mass index is relevant to suicidal
      ideation and self-harming behavior in Japanese adolescents.
AB  - Whether a low body mass index (BMI) is directly associated with a high risk of
      suicidal ideation or self-harming behavior in adolescents is still inconclusive.
      This study has, therefore, evaluated the relevance of BMI to suicidal ideation
      and self-harming behavior after controlling for body weight perception (BWP) and
      other potential confounding factors. BMI, BWP, suicidal ideation, and self
      harming behavior were all assessed using a self-report questionnaire administered
      to 18,104 Japanese adolescents. Potential confounding factors were also
      evaluated. The data were then analyzed using bivariate and multivariate logistic
      regression. Low BMI was associated with suicidal ideation and deliberate self
      harm when controlling for sex, age, drug use, emotional distress, and BWP. Low
      BMI may be an independent risk factor for suicidal ideation and deliberate self
      harming behavior in Japanese adolescents.

PMID- 22456584
TI  - Hallucination-like experiences in the nonclinical population.
AB  - Unusual subjective experiences are relatively common in the general population
      and have been associated with an increased level of vulnerability to psychosis.
      The current study aimed to a) determine the distribution of hallucination-like
      experiences (HLEs) in a community sample of young adults, b) investigate their
      dimensional subtypes, and c) test the association of HLEs with indicators of poor
      mental health. Four hundred thirty-seven participants (men, 41%) completed a
      battery of questionnaires including the 16-item Launay-Slade Hallucination Scale
      (LSHS), the 12-item General Health Questionnaire (GHQ-12) and the 21-item Peters
      et al. Delusions Inventory (PDI). The LSHS correlated significantly with GHQ-12
      and PDI. Individuals with higher levels of psychological distress were found to
      report higher frequencies of the HLEs compared with those in the reference range.
      Exploratory factor analysis of LSHS produced a four-factor solution: a) "auditory
      and visual HLEs," b) "multisensory HLEs," c) "intrusive thoughts," and d) "vivid
      daydreams." The current results provide further support for the multidimensional
      nature of hallucination proneness in the general population and indicate that
      some HLEs (particularly those related to intrusiveness of thought) are associated
      with a lower level of perceived well-being.

PMID- 22456585
TI  - Cognitive impairments in schizophrenia and schizoaffective disorder: relationship
      with clinical characteristics.
AB  - The present study aimed to compare population-based familial samples of patients
      with schizophrenia (n = 218) and schizoaffective disorder (n = 62) and a healthy
      control group (n = 123). Patients with schizoaffective disorder outperformed
      patients with schizophrenia in verbal ability, processing speed, visual working
      memory, and verbal memory. When compared with controls, patients with
      schizoaffective disorder also had a generalized cognitive impairment. Adjusting
      for clinical characteristics removed significant differences between the patient
      groups. Irrespective of the diagnosis, patients with the most severe negative
      symptoms and highest dose of antipsychotics had the most severe cognitive
      impairments, whereas mood symptoms were not related to cognitive performance. In
      conclusion, people with schizoaffective disorder have severe cognitive
      impairments, but the impairments are milder than in schizophrenia. Mood symptoms
      may not explain the difference between the diagnostic groups in cognitive
      functions, but the difference may be related to differences in the severity of
      negative symptoms.

PMID- 22456586
TI  - Defense mechanisms in congenital and acquired facial disfigurement: a clinical
      empirical study.
AB  - It is of clinical interest to investigate the degree to which patients with
      facial disfigurement use defense styles. Therefore, 59 adults born with rare
      facial clefts, 59 patients with facial deformities acquired at an adult age, and
      a reference group of 141 adults without facial disfigurements completed
      standardized questionnaires. There was a significant difference between the group
      with and the group without disfigurements on immature defense styles, with the
      disfigured group using the immature style more frequently. There was a trend for
      the nondisfigured group to use more mature defense styles. No difference between
      congenital and acquired groups was seen on individual types of defense style.
      Self-esteem had the strength to differentiate mature and immature defense styles
      within our disfigured groups. The association of low self-esteem and the
      utilization of immature defense styles suggests that professional help may tailor
      treatment on discussing immature defense style and problems triggering or
      maintaining this style.

PMID- 22456587
TI  - The interactive effect of blame attribution with characteristics of child sexual
      abuse on posttraumatic stress disorder.
AB  - The present study examined the role of attributions of blame for child sexual
      abuse (CSA) in posttraumatic stress disorder (PTSD) symptoms. The interactive
      effects of attribution of blame with characteristics of abuse on PTSD were
      studied. A sample of 151 female victims of CSA participated in the study. Self
      blame and family blame were related to higher PTSD scores, whereas perpetrator
      blame was not related to PTSD. The strength of the relationship between blame and
      PTSD score was higher in cases of more severe, isolated, and extrafamilial abuse.
      The findings suggest that diminishing self-blame attributions may be particularly
      advantageous in cases of isolated and extrafamilial CSA, whereas diminishing
      family blame would be more advantageous in cases of severe abuse.

PMID- 22456588
TI  - Sex differences in neuropsychological performance as an effect of human
      immunodeficiency virus infection: a pilot study in Zambia, Africa.
AB  - This study examined whether there are neuropsychological performance differences
      between human immunodeficiency virus-seropositive participants being followed at
      a University of Zambia clinic and demographically comparable seronegative
      controls being tested for infection in the same setting. All participants were
      administered a standardized neurocognitive test battery that has been found
      sensitive to HIV-associated Neurocognitive Disorder in the United States and
      internationally (e.g., in China, India, Romania, and Cameroon). The test battery
      was found to be applicable to a Zambian population. A clear HIV effect was seen
      with a medium to large overall effect size (Cohen d = 0.74). However, it was only
      the female seropositive participants who showed this HIV effect. HIV can result
      in neuropsychological deficits in Zambia, where clade C of the virus dominates.
      It is suggested that the HIV-infected women are more at risk of developing
      cognitive deficits than are men in this population, possibly because of sex
      related social, financial, and healthcare disadvantages. However, further
      analyses are required regarding this conclusion because the finding was a result
      of an unplanned subanalysis.

PMID- 22456589
TI  - Construct validity of the Schwartz Outcome Scale: validation using a 28-day
      inpatient chemical rehabilitation patient sample.
AB  - The Schwartz Outcome Scale-10 (SOS-10) is a 10-item self-report that measures
      quality of life and psychological well-being. It is easy to administer and score,
      and past research has revealed its utility, validity, and reliability with
      different samples (i.e., clinical and nonclinical) and in different clinical
      settings (i.e., inpatient, outpatient, nonpsychiatry medical settings). The
      present study looks to investigate the utility of the SOS-10 in measuring
      psychological well-being and quality of life with the 28-day inpatient chemical
      dependency sample. In addition, the current study looks to investigate its
      ability to be used as a treatment outcome measure for chemical-dependent
      inpatients. The results revealed that the SOS-10 was associated with aspects of
      interpersonal dependency and alexithymia in predicted ways. The SOS-10 was
      positively associated to "Healthy Dependence" and negatively related to
      alexithymia and "Destructive Overdependence" and "Dysfunctional Detachment." The
      results also showed that the SOS-10 showed healthy change from admission to
      discharge and that this change was paralleled by healthy change in interpersonal
      dependency and alexithymia.

PMID- 22456590
TI  - The Multidimensional Loss Scale: validating a cross-cultural instrument for
      measuring loss.
AB  - The Multidimensional Loss Scale (MLS) represents the first instrument designed
      specifically to index Experience of Loss Events and Loss Distress across multiple
      domains (cultural, social, material, and intrapersonal) relevant to refugee
      settlement. Recently settled Burmese adult refugees (N = 70) completed a
      questionnaire battery, including MLS items. Analyses explored MLS internal
      consistency, convergent and divergent validity, and factor structure. Cronbach
      alphas indicated satisfactory internal consistency for Experience of Loss Events
      (0.85) and Loss Distress (0.92), reflecting a unitary construct of
      multidimensional loss. Loss Distress did not correlate with depression or anxiety
      symptoms and correlated moderately with interpersonal grief and trauma symptoms,
      supporting divergent and convergent validity. Factor analysis provided
      preliminary support for a five-factor model: Loss of Symbolic Self, Loss of
      Interdependence, Loss of Home, Interpersonal Loss, and Loss of Intrapersonal
      Integrity. Received well by participants, the new scale shows promise for
      application in future research and practice.

PMID- 22456591
TI  - Effect of video self-observations vs. observations of others on insight in
      psychotic disorders.
AB  - Improving insight in patients with schizophrenia and related disorders is a
      worthwhile goal. Previous work has suggested that patients' insight may improve
      if they see videos of themselves taken when ill. Our aim was to test the
      hypothesis that schizophrenia patients improve their insight after viewing videos
      of themselves when unwell more so than after viewing an actor. Forty patients
      admitted with an acute psychotic disorder underwent a videotaped recording of a
      clinical interview. The patients were then randomized to viewing this or a
      "control" video of a same-sex actor displaying psychotic symptoms approximately 3
      weeks later. Insight, psychopathology, and mood were assessed before and 24 to 48
      hours after viewing the videos. All participants showed general improvement
      across all measures. There was a trend for scores on the Schedule for the
      Assessment of Insight to improve more in those who viewed themselves when ill,
      but there were no clear statistically significant differences between the "self"
      and "other" video groups. In conclusion, video self-confrontation seems to be a
      safe and potentially effective means of enhancing insight, but evidence for a
      specific effect is lacking.

PMID- 22456593
TI  - Solvatochromic investigation of highly fluorescent 2-aminobithiophene
      derivatives.
AB  - The solvatochromic and electrochemical properties of electronic push-pull 2
      aminobithiophenes consisting of an aldehyde and nitro withdrawing groups were
      examined. With the use of an integrating sphere, the absolute quantum yields of
      the bithiophenes were measured. They were found to be highly fluorescent (Phifl >
      70%), provided the nitro group was not located in the 4'-position. High
      fluorescence yields were observed regardless of solvent, except for alcohols,
      notably methanol and ethanol. Cryofluorescence was used to probe the bithiophene
      temperature dependent excited state deactivation modes. The singlet excited state
      deactivation mode other than fluorescence was found to be internal conversion
      involving rotation around the thiophene-thiophene bond. Deactivation by
      intersystem crossing to the triplet state occurred in ca. 40% only for the
      unsubstituted 2-aminobithiophene. In contrast, the fluorescence was quenched by
      photoinduced intramolecular electron transfer when the nitro group was located in
      the 4'-position of the bithiophene. Both the absorbance and fluorescence of the
      bithiophenes were found to be solvatochromic with more pronounced solvent
      dependent shifts being observed with the fluorescence. In fact, both the
      fluorescence and Stokes shifts were linearly dependent on the ET(30) solvent
      parameter. Deviations from the linear trend of the Stokes shift with ET(30) were
      observed in ethanol and methanol as a result of intermolecular hydrogen
      abstraction from the solvent and by the excited nitro group. The oxidation
      potential of the bithiophenes was also highly dependent on the type and number of
      the electron withdrawing substituents, with values ranging between 0.8 and 1.2 V
      vs. SCE. 

PMID- 22456592
TI  - Peritraumatic dissociation after loss: latent structure and associations with
      psychopathology.
AB  - This study investigated the factor-structure of retrospectively assessed
      peritraumatic dissociation in the moments surrounding the death of a loved one
      and concurrent and prospective associations of such peritraumatic dissociation
      with loss-related emotional distress. Data were available from 168 people,
      bereaved in the preceding year. They completed the Peritraumatic Dissociative
      Experiences Questionnaire with their loss as the index event, together with
      measures of prolonged grief disorder, depression, and posttraumatic stress
      disorder; 117 completed symptom measures again 1 year later. Confirmatory factor
      analysis comparing the fit of four competing models showed that the eight-item
      one-factor model found in the first study using the Peritraumatic Dissociative
      Experiences Questionnaire provided the best fit to the data. Peritraumatic
      dissociation predicted concurrent and prospective symptom levels even when
      controlling for neuroticism and demographic and loss-related variables.

PMID- 22456594
TI  - Analysis of genetic polymorphism of the HLA-B and HLA-DR loci in patients with
      dermatophytic onychomycosis and in their first-degree relatives.
AB  - Onychomycosis is known to have predisposing factors and a high prevalence within
      families that cannot be explained by within-family transmission. We determined
      the frequency of HLA-B and HLA-DR haplotypes in 25 families of Mexican patients
      with onychomycosis in order to define the role of the class II major
      histocompatibility complex (MHC) in genetic susceptibility to this infection.
      Seventy-eight subjects participated in the study, 47 with onychomycosis and 31
      healthy individuals. The frequencies of the HLA-B and HLA-DR haplotypes were
      compared with those found in first-degree relatives without onychomycosis and in
      a historic control group of healthy individuals. The frequencies in the controls
      were similar to those of the healthy relatives of the patients. However, on
      comparison of the patients with historic controls, we detected a higher frequency
      of the HLA-DR8 haplotype (P=.03; odds ratio, 1.89; 95% confidence interval, 0.98
      36). These findings suggest that there are polymorphisms in genes of the MHC that
      increase susceptibility to onychomycosis, particularly haplotype HLA-DR8.

PMID- 22456595
TI  - Pellagra: a clinical, histopathological, and epidemiological study of 7 cases.
AB  - BACKGROUND AND OBJECTIVES: In the developed world, pellagra is a rare condition
      that is restricted to a small number of at-risk groups. It mainly affects
      alcoholic patients and those with dietary deficiencies, with intestinal
      malabsorption, or in treatment with certain drugs. The aim of this study was to
      analyze the clinical, histopathological, and epidemiological characteristics of
      patients diagnosed with pellagra in our hospital and to compare the results with
      the findings traditionally described for this disease. PATIENTS AND METHODS: We
      undertook a retrospective study of patients with clinical or pathological
      evidence of pellagra who were seen in our hospital between 1998 and 2009.
      RESULTS: Seven patients met the inclusion criteria. All were men and the most
      common predisposing factors were alcoholism and dietary deficiency. All exhibited
      photosensitivity mainly affecting the forearms and the upper surface of the feet,
      where the lesions were more severe. The most consistent histopathological
      findings were the presence of dilated blood vessels with extravasation and little
      or no inflammatory infiltrate. Various changes were observed in the epidermis,
      including those suggestive of mild pellagra, such as epidermal pallor and some
      degree of ballooning of the keratinocytes. Other abnormalities such as epidermal
      necrosis and hyperkeratosis were also observed. In most patients, pellagra was
      not initially suspected. Additional noncutaneous findings were observed in almost
      all cases. CONCLUSIONS: Pellagra should be ruled out in patients with lesions on
      sun-exposed areas. Predisposing factors for pellagra should be assessed along
      with the social situation of patients and the presence of digestive or
      neurological abnormalities.

PMID- 22456596
TI  - Editorial note.

PMID- 22456597
TI  - Thio-Pybox and Thio-Phebox complexes of chromium, iron, cobalt and nickel and
      their application in ethylene and butadiene polymerisation catalysis.
AB  - A series of bis(thiazolinyl)- and bis(thiazolyl)pyridine Thio-Pybox ligands and
      their metal complexes of chromium(III), iron(II), cobalt(II) and nickel(II) has
      been prepared, as well as a nickel(II) complex containing a monoanionic
      bis(thiazolinyl)phenyl Thio-Phebox ligand. These new metal complexes have been
      characterised and used as catalysts, in combination with the co-catalyst MAO, for
      the polymerisation of ethylene and for the polymerisation of butadiene. In the
      case of ethylene polymerisation, the Thio-Pybox and Thio-Phebox metal complexes
      have shown relatively low polymerisation activities, much lower compared to the
      related bis(imino)pyridine complexes of the same metals. In the polymerisation of
      butadiene, several Thio-Pybox cobalt(II) complexes show very high activities,
      significantly higher than the other metal complexes with the same ligand. It is
      the metal, rather than the ligand, that appears to have the most profound effect
      on the catalytic activity in butadiene polymerisation, unlike in the
      polymerisation of ethylene, where bis(imino)pyridine ligands provide highly
      active catalysts for a range of 1st row transition metals.

PMID- 22456598
TI  - Chronic exposure to fine particles and mortality: an extended follow-up of the
      Harvard Six Cities study from 1974 to 2009.
AB  - BACKGROUND: Epidemiologic studies have reported associations between fine
      particles (aerodynamic diameter <= 2.5 um; PM2.5) and mortality. However,
      concerns have been raised regarding the sensitivity of the results to model
      specifications, lower exposures, and averaging time. OBJECTIVE: We addressed
      these issues using 11 additional years of follow-up of the Harvard Six Cities
      study, incorporating recent lower exposures. METHODS: We replicated the
      previously applied Cox regression, and examined different time lags, the shape of
      the concentration-response relationship using penalized splines, and changes in
      the slope of the relation over time. We then conducted Poisson survival analysis
      with time-varying effects for smoking, sex, and education. RESULTS: Since 2001,
      average PM2.5 levels, for all six cities, were < 18 ug/m3. Each increase in PM2.5
      (10 ug/m3) was associated with an adjusted increased risk of all-cause mortality
      (PM2.5 average on previous year) of 14% [95% confidence interval (CI): 7, 22],
      and with 26% (95% CI: 14, 40) and 37% (95% CI: 7, 75) increases in cardiovascular
      and lung-cancer mortality (PM2.5 average of three previous years), respectively.
      The concentration-response relationship was linear down to PM2.5 concentrations
      of 8 ug/m3. Mortality rate ratios for PM2.5 fluctuated over time, but without
      clear trends despite a substantial drop in the sulfate fraction. Poisson models
      produced similar results. CONCLUSIONS: These results suggest that further public
      policy efforts that reduce fine particulate matter air pollution are likely to
      have continuing public health benefits.

PMID- 22456599
TI  - Electrical and thermal properties of a carbon nanotube/polycrystalline BiFeO3/Pt
      photovoltaic heterojunction with CdSe quantum dots sensitization.
AB  - Electrical and thermal properties of a carbon nanotube (CNT)/multiferroic
      BiFeO(3) (BFO)/Pt photovoltaic heterojunction are investigated for the first
      time. Enhanced photovoltaic properties (J(sc)~ 2.1 MUA cm(-2) and V(oc)~ 0.47 V),
      as compared to the traditional polycrystalline BFO with indium tin oxide (ITO) as
      the top electrode, are observed due to the unique properties of CNT. An
      equivalent electrical and thermal model is constructed based on the energy band
      diagram of the CNT/BFO/Pt heterojunction for the first time and the carriers'
      transportation behavior is depicted theoretically. The influence of CdSe quantum
      dots (QDs) sensitization on the photovoltaic properties is presented, and a clear
      improvement of ~4 fold in photocurrent density is observed.

PMID- 22456600
TI  - Bone-specific alkaline phosphatase concentrations are less variable than those of
      parathyroid hormone in stable hemodialysis patients.
AB  - Abnormalities of bone mineral metabolism and vascular calcification are prevalent
      in patients with kidney failure. Clinical management is based on biochemical
      targets, in particular parathyroid hormone (PTH) concentrations, but this has
      many limitations including high biological variation. A possible alternative is
      bone-specific alkaline phosphatase (ALP); therefore, we evaluated the biological
      variation of this marker in patients undergoing hemodialysis. Bone ALP was
      measured in non-fasting serum samples taken twice a week over a 6-week period in
      22 stable hemodialysis patients and 12 healthy volunteers. The within-individual
      coefficients of variance were calculated and used to derive the critical
      difference required to be certain that an observed change was significant. The
      coefficient of variance for bone ALP was significantly higher in hemodialysis
      patients compared to healthy individuals. Seven samples were required to estimate
      the homeostatic set point of bone ALP, within 10%, in a hemodialysis patient. The
      concentration of serial bone ALP measurements would need to change by 36% between
      any two measurements before it can be considered a significant change. Since the
      biological variation of bone ALP is less than half that reported for PTH, our
      study provides further support for the use of bone ALP as an alternative marker
      of bone mineral metabolism in the setting of chronic kidney disease-mineral and
      bone disorder.

PMID- 22456601
TI  - Acquired and genetic complement abnormalities play a critical role in dense
      deposit disease and other C3 glomerulopathies.
AB  - Dense deposit disease and glomerulonephritis with isolated C3 deposits are
      glomerulopathies characterized by deposits of C3 within or along the glomerular
      basement membrane. Previous studies found a link between dysregulation of the
      complement alternative pathway and the pathogenesis of these diseases. We
      analyzed the role of acquired and genetic complement abnormalities in a cohort of
      134 patients, of whom 29 have dense deposit disease, 56 have glomerulonephritis
      with isolated C3 deposits, and 49 have primary membranoproliferative
      glomerulonephritis type I, with adult and pediatric onset. A total of 53 patients
      presented with a low C3 level, and 65 were positive for C3 nephritic factor that
      was significantly more frequently detected in patients with dense deposit disease
      than in other histological types. Mutations in CFH and CFI genes were identified
      in 24 patients associated with a C3 nephritic factor in half the cases. We found
      evidence for complement alternative pathway dysregulation in 26 patients with
      membranoproliferative glomerulonephritis type I. The complement factor H Y402H
      variant was significantly increased in dense deposit disease. We identified one
      at-risk membrane cofactor protein (MCP) haplotype for glomerulonephritis with
      isolated C3 deposits and membranoproliferative glomerulonephritis type I. Thus,
      our results suggest a critical role of fluid-phase alternative pathway
      dysregulation in the pathogenesis of C3 glomerulopathies as well as in immune
      complex-mediated glomerular diseases. The localization of the C3 deposits may be
      under the influence of MCP expression.

PMID- 22456603
TI  - New insights into urea and glucose handling by the kidney, and the urine
      concentrating mechanism.
AB  - The mechanism by which urine is concentrated in the mammalian kidney remains
      incompletely understood. Urea is the dominant urinary osmole in most mammals and
      may be concentrated a 100-fold above its plasma level in humans and even more in
      rodents. Several facilitated urea transporters have been cloned. The phenotypes
      of mice with deletion of the transporters expressed in the kidney have challenged
      two previously well-accepted paradigms regarding urea and sodium handling in the
      renal medulla but have provided no alternative explanation for the accumulation
      of solutes that occurs in the inner medulla. In this review, we present evidence
      supporting the existence of an active urea secretion in the pars recta of the
      proximal tubule and explain how it changes our views regarding intrarenal urea
      handling and UT-A2 function. The transporter responsible for this secretion could
      be SGLT1, a sodium-glucose cotransporter that also transports urea. Glucagon may
      have a role in the regulation of this secretion. Further, we describe a possible
      transfer of osmotic energy from the outer to the inner medulla via an intrarenal
      Cori cycle converting glucose to lactate and back. Finally, we propose that an
      active urea transporter, expressed in the urothelium, may continuously reclaim
      urea that diffuses out of the ureter and bladder. These hypotheses are all based
      on published findings. They may not all be confirmed later on, but we hope they
      will stimulate further research in new directions.

PMID- 22456604
TI  - Solubility of gold nanoparticles as a function of ligand shell and alkane
      solvent.
AB  - The solubility of ca. 5.0 nm gold nanoparticles was studied systematically as a
      function of ligand shell and solvent. The ligands were octane-, decane-, dodecane
      and hexadecanethiols; the solvents were the n-alkanes from hexane to hexadecane
      and toluene. Supernatant concentrations in equilibrium with precipitated
      superclusters of nanoparticles were measured at room temperature (23  degrees C)
      with UV-Vis spectrophotometry. The solubility of nanoparticles ligated with
      decane- and dodecanethiol was greatest in n-decane and n-dodecane, respectively.
      In contrast, the solubility of nanoparticles ligated with octane- and
      hexadecanethiol showed decreasing solubility with increasing solvent chain
      length. In addition the solubility of the octanethiol ligated system showed a
      nonmonotonic solvent carbon number functionality with even numbered solvents
      being better solvents than neighboring odd numbered solvents.

PMID- 22456605
TI  - Impact of microRNA regulation on variation in human gene expression.
AB  - MicroRNAs (miRNAs) are endogenously expressed small RNAs that regulate expression
      of mRNAs at the post-transcriptional level. The consequence of miRNA regulation
      is hypothesized to reduce the expression variation of target genes. However, it
      is possible that mutations in miRNAs and target sites cause rewiring of the miRNA
      regulatory networks resulting in increased variation in gene expression. By
      examining variation in gene expression patterns in human populations and between
      human and other primate species, we find that miRNAs have stabilized expression
      of a small number of target genes during primate evolution. Compared with genes
      not regulated by miRNAs, however, genes regulated by miRNAs overall have higher
      expression variation at the population level, and they display greater variation
      in expression among human ethnic groups or between human and other primate
      species. By integrating expression data with genotypes determined in the HapMap 3
      and the 1000 Genomes Projects, we found that expression variation in miRNAs,
      genetic variants in miRNA loci, and mutations in miRNA target sites are important
      sources of elevated expression variation of miRNA target genes. A reasonable case
      can be made that natural selection is driving this pattern of variation.

PMID- 22456602
TI  - The effect of frequent hemodialysis on nutrition and body composition: frequent
      Hemodialysis Network Trial.
AB  - We investigated the effects of frequency of hemodialysis on nutritional status by
      analyzing the data in the Frequent Hemodialysis Network Trial. We compared
      changes in albumin, body weight, and composition among 245 patients randomized to
      six or three times per week in-center hemodialysis (Daily Trial) and 87 patients
      randomized to six times per week nocturnal or three times per week conventional
      hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial,
      there were no significant differences between groups in changes in serum albumin
      or the equilibrated protein catabolic rate by 12 months. There was a significant
      relative decrease in predialysis body weight of 1.5 +/- 0.2 kg in the six times
      per week group at 1 month, but this significantly rebounded by 1.3 +/- 0.5 kg
      over the remaining 11 months. Extracellular water (ECW) decreased in the six
      times per week compared with the three per week hemodialysis group. There were no
      significant between-group differences in phase angle, intracellular water, or
      body cell mass (BCM). In the Nocturnal Trial, there were no significant between
      group differences in any study parameter. Any gain in 'dry' body weight
      corresponded to increased adiposity rather than muscle mass but was not
      statistically significant. Thus, frequent in-center hemodialysis reduced ECW but
      did not increase serum albumin or BCM while frequent nocturnal hemodialysis
      yielded no net effect on parameters of nutritional status or body composition.

PMID- 22456608
TI  - Theory of the Overhauser effect in the pulsed mode of EPR pumping: exploiting the
      advantages of coherent electron spin motion.
AB  - A theoretical approach is proposed to describe Overhauser-type Dynamic Nuclear
      Polarization (DNP) for pulsed EPR pumping by application of a train of short
      pulses with a duration on the nanosecond time scale. We obtained an elegant
      general expression for the NMR enhancement provided by the DNP effect. The
      expression for the enhancement is similar to that known for cw-pumping except for
      the saturation factor, which is re-defined as the deviation of the electron spin
      magnetization from its equilibrium value averaged over the cycle of the pulse
      sequence. It is shown that one can achieve the maximal theoretically allowed NMR
      enhancement for pulsed pumping even when the duty cycle of pumping is low. This
      becomes possible because coherent motion of the electron spins in the B(1)-field
      is exploited, a key feature of the pulsed DNP experiment also enabling
      optimization of the achievable NMR enhancement. The dependence of the effect on
      the duty cycle, pulse duration and electron spin relaxation times has been
      studied in detail. Once the lines in the EPR spectrum are inhomogeneously
      broadened, higher DNP effects are expected in the pulsed pumping mode than in the
      cw-mode for the same total power of microwave irradiation. The theoretical
      results are in good agreement with experimental data obtained for the pumping
      frequencies of 300 MHz and 1.4 GHz.

PMID- 22456606
TI  - Predictive regulatory models in Drosophila melanogaster by integrative inference
      of transcriptional networks.
AB  - Gaining insights on gene regulation from large-scale functional data sets is a
      grand challenge in systems biology. In this article, we develop and apply methods
      for transcriptional regulatory network inference from diverse functional genomics
      data sets and demonstrate their value for gene function and gene expression
      prediction. We formulate the network inference problem in a machine-learning
      framework and use both supervised and unsupervised methods to predict regulatory
      edges by integrating transcription factor (TF) binding, evolutionarily conserved
      sequence motifs, gene expression, and chromatin modification data sets as input
      features. Applying these methods to Drosophila melanogaster, we predict ~300,000
      regulatory edges in a network of ~600 TFs and 12,000 target genes. We validate
      our predictions using known regulatory interactions, gene functional annotations,
      tissue-specific expression, protein-protein interactions, and three-dimensional
      maps of chromosome conformation. We use the inferred network to identify putative
      functions for hundreds of previously uncharacterized genes, including many in
      nervous system development, which are independently confirmed based on their
      tissue-specific expression patterns. Last, we use the regulatory network to
      predict target gene expression levels as a function of TF expression, and find
      significantly higher predictive power for integrative networks than for motif or
      ChIP-based networks. Our work reveals the complementarity between physical
      evidence of regulatory interactions (TF binding, motif conservation) and
      functional evidence (coordinated expression or chromatin patterns) and
      demonstrates the power of data integration for network inference and studies of
      gene regulation at the systems level.

PMID- 22456607
TI  - A genome-wide analysis of common fragile sites: what features determine
      chromosomal instability in the human genome?
AB  - Chromosomal common fragile sites (CFSs) are unstable genomic regions that break
      under replication stress and are involved in structural variation. They
      frequently are sites of chromosomal rearrangements in cancer and of viral
      integration. However, CFSs are undercharacterized at the molecular level and thus
      difficult to predict computationally. Newly available genome-wide profiling
      studies provide us with an unprecedented opportunity to associate CFSs with
      features of their local genomic contexts. Here, we contrasted the genomic
      landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of
      nonfragile sites, using multiple logistic regression. We also analyzed aCFS
      breakage frequencies as a function of their genomic landscape, using standard
      multiple regression. We show that local genomic features are effective predictors
      both of regions harboring aCFSs (explaining ~77% of the deviance in logistic
      regression models) and of aCFS breakage frequencies (explaining ~45% of the
      variance in standard regression models). In our optimal models (having highest
      explanatory power), aCFSs are predominantly located in G-negative chromosomal
      bands and away from centromeres, are enriched in Alu repeats, and have high DNA
      flexibility. In alternative models, CpG island density, transcription start site
      density, H3K4me1 coverage, and mononucleotide microsatellite coverage are
      significant predictors. Also, aCFSs have high fragility when colocated with
      evolutionarily conserved chromosomal breakpoints. Our models are predictive of
      the fragility of aCFSs mapped at a higher resolution. Importantly, the genomic
      features we identified here as significant predictors of fragility allow us to
      draw valuable inferences on the molecular mechanisms underlying aCFSs.

PMID- 22456609
TI  - Mesonephric adenocarcinomas of the uterine cervix and corpus: HPV-negative
      neoplasms that are commonly PAX8, CA125, and HMGA2 positive and that may be
      immunoreactive with TTF1 and hepatocyte nuclear factor 1-beta.
AB  - Mesonephric adenocarcinomas are rare neoplasms that most commonly arise in the
      uterine cervix and exceptionally rarely in the uterine corpus. Although the
      morphologic features of these neoplasms are well described, there has been
      relatively limited investigation of the immunoprofile. We report a series of 8
      mesonephric adenocarcinomas arising in the uterine cervix (7 cases) and corpus (1
      case) and undertake a comprehensive immunohistochemical analysis. This includes
      markers that have not been investigated previously in mesonephric adenocarcinomas
      but that are commonly used in gynecologic pathology and may be undertaken when
      other, mainly Mullerian, adenocarcinomas are considered in the differential
      diagnosis. Linear array human papillomavirus (HPV) genotyping was also performed.
      Our results broadly confirm the immunohistochemical profile demonstrated in
      previous studies with the majority of mesonephric adenocarcinomas staining
      positively with CD10 (6 of 8), epithelial membrane antigen (8 of 8), vimentin (8
      of 8), and calretinin (7 of 8). Estrogen receptor was positive in 2,
      carcinoembryonic antigen in 3, and inhibin in 4 cases. p16 was positive in 5
      cases (1 diffuse and strong), despite all being HPV negative (in 1 case, there
      was insufficient DNA for HPV analysis). Novel findings in our study were the
      demonstration of nuclear positivity with PAX8 and HMGA2 in 7 cases, CA125
      immunoreactivity in all 8 cases, and TTF1 and hepatocyte nuclear factor 1-beta
      staining in 3 cases. As PAX8, CA125, HMGA2, and hepatocyte nuclear factor 1-beta
      are commonly positive in a variety of Mullerian adenocarcinomas arising in the
      female genital tract, this may result in diagnostic confusion. All cases were WT1
      negative.

PMID- 22456610
TI  - The clinicopathologic features of YWHAE-FAM22 endometrial stromal sarcomas: a
      histologically high-grade and clinically aggressive tumor.
AB  - Endometrial stromal sarcoma (ESS) is a genetically heterogenous group of uterine
      sarcomas, of which almost half are associated with JAZF1 rearrangement. We
      recently identified a novel genetic fusion between YWHAE and FAM22A/B in ESS
      harboring t(10;17)(q22;p13) and herein describe the clinicopathologic features of
      13 YWHAE-FAM22 ESS cases (11 primary and 3 metastatic) and compare them with 20
      ESS cases with JAZF1 rearrangement. Ten of 11 primary uterine tumors contained
      morphologically high-grade areas composed of round cells arranged in nests with a
      delicate stromal capillary network. The tumor cells showed large nuclei with
      irregular nuclear contours and significant mitotic activity (>10 mitoses/10 HPF)
      in addition to focal tumor necrosis, in contrast to JAZF1 ESS, which lacked a
      nested growth pattern, were composed of cells with small round/oval nuclei, and
      typically had <5 MF/10 HPF. In 7 of the 11 uterine tumors, there was an
      additional cytologically bland and mitotically weakly active spindle cell
      component with a fibrous/fibromyxoid stroma (ESS, fibromyxoid variant). Two
      metastatic tumors (pulmonary) also contained round cell and spindle cell
      components, whereas 1 metastasis (vaginal) was composed solely of the spindle
      cell component. In both primary and metastatic tumors, the spindle cells were
      diffusely positive for estrogen and progesterone receptors and CD10, in contrast
      to the round cell areas, which were negative. Clinically, 10 of 12 patients with
      YWHAE-FAM22 ESS presented with FIGO stages II to III disease, in contrast to only
      4 of 16 patients with JAZF1 ESS presenting with stages II to III disease
      (P<0.05). Tumors with YWHAE-FAM22 rearrangements constitute a distinct group of
      ESS, which is associated with high-grade morphology and aggressive clinical
      behavior compared to JAZF1 ESS. Thus, their distinction from typical JAZF1 ESS is
      important for prognostic and therapeutic purposes.

PMID- 22456611
TI  - Perivascular epithelioid cell tumors (PEComas) harboring TFE3 gene rearrangements
      lack the TSC2 alterations characteristic of conventional PEComas: further
      evidence for a biological distinction.

PMID- 22456612
TI  - [Hereditary cutaneous leiomyomatosis].
AB  - The occurrence of multiple cutaneous leiomyomas can be indicative of hereditary
      cutaneous leiomyomatosis. This autosomal dominant disorder is due to germline
      mutations in the fumarate hydratase (FH) gene. Associations with uterine myomas
      and renal cell carcinomas have been described and are referred to as Multiple
      Cutaneous and Uterine Leiomyomas (MCUL) or Hereditary Leiomyomatosis and Renal
      Cell Cancer (HLRCC), respectively. A 34-year-old man presented with multiple red
      brown papules and nodules. After histopathologic confirmation of piloleiomyomas,
      we made the diagnosis of hereditary cutaneous leiomyomatosis. Taking into
      consideration the aforementioned complications, close interdisciplinary
      management of these patients and regular screening examinations within affected
      families are mandatory.

PMID- 22456614
TI  - Development of hepatitis C virus production reporter-assay systems using two
      different hepatoma cell lines.
AB  - A hepatitis C virus (HCV) infection system was developed previously using the HCV
      JFH-1 strain (genotype 2a) and HuH-7 cells, and this cell culture is so far the
      only robust production system for HCV. In patients with chronic hepatitis C, the
      virological effects of pegylated interferon and ribavirin therapy differ
      depending on the HCV strain and the genetic background of the host. Recently, we
      reported the hepatoma-derived Li23 cell line, in which the JFH-1 life cycle is
      reproduced at a level almost equal to that in HuH-7-derived RSc cells. To monitor
      the HCV life cycle more easily, we here developed JFH-1 reporter-assay systems
      using both HuH-7- and Li23-derived cell lines. To identify any genetic mutations
      by long-term cell culture, HCV RNAs in HuH-7 cells were amplified 130 days after
      infection and subjected to sequence analysis to find adaptive mutation(s) for
      robust virus replication. We identified two mutations, H2505Q and V2995L, in the
      NS5B region. V2995L but not H2505Q enhanced JFH-1 RNA replication. However, we
      found that H2505Q but not V2995L enhanced HCV RNA replication of strain O
      (genotype 1b). We also selected highly permissive D7 cells by serial subcloning
      of Li23 cells. The expression levels of claudin-1 and Niemann-Pick C1-like 1 in
      D7 cells are higher than those in parental Li23 cells. In this study, we
      developed HCV JFH-1 reporter-assay systems using two distinct hepatoma cell
      lines, HuH-7 and Li23. The mutations in NS5B resulted in different effects on
      strains O and JFH-1 HCV RNA replication.

PMID- 22456613
TI  - Epidemic history of hepatitis C virus infection in two remote communities in
      Nigeria, West Africa.
AB  - We investigated the molecular epidemiology and population dynamics of HCV
      infection among indigenes of two semi-isolated communities in North-Central
      Nigeria. Despite remoteness and isolation, ~15% of the population had serological
      or molecular markers of hepatitis C virus (HCV) infection. Phylogenetic analysis
      of the NS5b sequences obtained from 60 HCV-infected residents showed that HCV
      variants belonged to genotype 1 (n=51; 85%) and genotype 2 (n=9; 15%). All
      sequences were unique and intermixed in the phylogenetic tree with HCV sequences
      from people infected from other West African countries. The high-throughput 454
      pyrosequencing of the HCV hypervariable region 1 and an empirical threshold error
      correction algorithm were used to evaluate intra-host heterogeneity of HCV
      strains of genotype 1 (n=43) and genotype 2 (n=6) from residents of the
      communities. Analysis revealed a rare detectable intermixing of HCV intra-host
      variants among residents. Identification of genetically close HCV variants among
      all known groups of relatives suggests a common intra-familial HCV transmission
      in the communities. Applying Bayesian coalescent analysis to the NS5b sequences,
      the most recent common ancestors for genotype 1 and 2 variants were estimated to
      have existed 675 and 286 years ago, respectively. Bayesian skyline plots suggest
      that HCV lineages of both genotypes identified in the Nigerian communities
      experienced epidemic growth for 200-300 years until the mid-20th century. The
      data suggest a massive introduction of numerous HCV variants to the communities
      during the 20th century in the background of a dynamic evolutionary history of
      the hepatitis C epidemic in Nigeria over the past three centuries.

PMID- 22456615
TI  - Baicalin induces apoptosis in SW620 human colorectal carcinoma cells in vitro and
      suppresses tumor growth in vivo.
AB  - In the United States, colorectal cancer (CRC) is the second most frequent
      malignancy and the fourth most common cause of cancer death. Baicalin, a flavone
      derivative isolated and purified from the dry root of Scutellaria, was assessed
      for its antitumor effects in human SW620 CRC cells. Baicalin (200 MUM) inhibited
      proliferation of SW620 cells. Baicalin (200 MUM) increased activities of caspase
      3, -8, and -9 in SW620 cells. Furthermore, flow cytometric analysis of baicalin
      treated SW620 cells showed an increase in sub-G1 cells, and the dihydroethidium
      assay showed significant enhancement of intracellular peroxide production in
      baicalin-treated cells. Addition of N-acetylcysteine prevented most of the
      baicalin-induced apoptosis, which in turn mediated cytotoxicity in human SW620
      cells. In vivo, baicalin (50 mg/kg/day, i.p.) treatment inhibited 55% of tumor
      growth in xenografted nude mice by 4 weeks, compared to that of the vehicle
      control (p < 0.05). Baicalin had no noteworthy influence on body weight. Thus, we
      suggest the development of baicalin as a potential leading antitumor agent in
      CRC.

PMID- 22456616
TI  - Synthesis and characterization of fullerene nanowhiskers by liquid-liquid
      interfacial precipitation: influence of C60 solubility.
AB  - Fullerene nanowhiskers (FNWs) composed of C(60) fullerene molecules were prepared
      using the liquid-liquid interfacial precipitation (LLIP) method in the carbon
      disulfide (CS(2)) and isopropyl alcohol (IPA) system. The electron microscopic
      images reveal the formation of non-tubular FNWs. The X-ray diffraction (XRD)
      pattern studies indicate the presence of fcc crystalline structure and unusual
      triclinic structure in the FNWs. The selected area electron diffraction pattern
      (SAED) analysis demonstrates the existence of triclinic and electron beam
      assisted fcc to tetragonal crystalline phase transformation. The formation of
      triclinic structure might be validated due to the partial polymerization of FNWs
      at C(60) saturated CS(2)-IPA interface. The high solubility of C(60) in CS(2)
      solvent system results in partial polymerization of FNWs. The polymerization of
      fullerene molecules in the FNWs has been further confirmed using Raman
      spectroscopy.

PMID- 22456617
TI  - Efficacy of prophylactic blood pressure lowering according to a standardized
      postoperative management protocol to prevent symptomatic cerebral hyperperfusion
      after direct revascularization surgery for moyamoya disease.
AB  - BACKGROUND: Cerebral hyperperfusion is a potential complication of superficial
      temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya
      disease, but the optimal postoperative management has not been determined.
      Aggressive blood pressure lowering is controversial because of the risk of
      ischemic complications. OBJECTIVE: To establish the optimal postoperative
      management protocol to prevent symptomatic cerebral hyperperfusion in moyamoya
      disease. METHODS: N-isopropyl-p-[(123)I]-iodoamphetamine single-photon emission
      computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 152
      hemispheres from 108 consecutive patients with moyamoya disease (2-69, mean 33.3
      years). Between 2004 and 2007 (period 1), 65 patients were maintained under
      normotensive conditions after 93 operations, and only patients with cerebral
      hyperperfusion underwent blood pressure lowering. Between 2008 and 2010 (period
      2), all 43 patients were prospectively subjected to intensive blood pressure
      lowering (<130 mm Hg of systolic blood pressure) immediately after 59 operations.
      Then the incidence of symptomatic cerebral hyperperfusion was compared between
      the two groups. RESULTS: Systolic blood pressure the day after surgery was
      significantly lower in period 2 (mean, 120.9 mm Hg) than in period 1 (133.9 mm
      Hg) (p < 0.0001). Symptomatic cerebral hyperperfusion was seen in 22 patients
      during period 1 (23 hemispheres, 24.7%), but only in 4 patients during period 2
      (6.7%, p = 0.0047). Multivariate analysis revealed that prophylactic blood
      pressure lowering was significantly associated with the prevention of symptomatic
      cerebral hyperperfusion (p = 0.015). Symptomatic cerebral hyperperfusion was
      relieved in all patients without developing a permanent neurological deficit due
      to cerebral hyperperfusion. CONCLUSION: Prophylactic blood pressure lowering
      prevents symptomatic cerebral hyperperfusion after STA-MCA anastomosis in
      patients with moyamoya disease. Accurate diagnosis of cerebral hyperperfusion and
      blood pressure lowering, and considering the severity of hemodynamic compromise
      in the contralateral and/or remote areas are essential for postoperative
      management of moyamoya disease.

PMID- 22456618
TI  - The endemic paraganglioma syndrome type 1: origin, spread, and clinical
      expression.
AB  - CONTEXT: Anecdotal evidence suggests a high incidence in Trentino, Italy, of head
      and neck paragangliomas (HNPGL), a rare autosomal dominant disease called
      paraganglioma type 1 syndrome and caused by germ-line mutations of the SDHD gene.
      OBJECTIVE: The aim of this study was to investigate the origin, spread, and
      clinical expression of the disease in this geographic region. DESIGN, SETTING,
      AND PARTICIPANTS: Trentino natives with HNPGL were recruited for establishing
      clinical expression of the disease, presence of a founder effect, and age of
      common ancestor. A large sample of the local population was recruited for
      determination of mutation prevalence and spread. MAIN OUTCOME MEASURES: SDHD
      genetic testing was offered to first-degree relatives, and clinical surveillance
      was offered to at-risk carriers. The hypothesis of a founder effect was explored
      by haplotype analysis, and time to the most recent common ancestor was estimated
      by decay of haplotype sharing over time. RESULTS: A total of 287 of the 540
      recruited individuals from 95 kindreds carried the SDHD c.341A>G p.Tyr114Cys
      mutation. The prevalent phenotype was bilateral or multiple HNPGL, with low
      prevalence of pheochromocytoma and malignant forms. Penetrance was high. A common
      ancestor was dated between the 14th and 15th century, with the mutation spreading
      from the Mocheni Valley, a geographic, cultural and, presumably, a genetic
      isolate to 1.5% of the region's population. CONCLUSIONS: A combination of
      particular demographic, geographical, and historical conditions has resulted in
      the oldest and largest SDHD founder effect so far characterized and has
      transformed a rare disease into an endemic disease with major public health
      implications.

PMID- 22456620
TI  - Differential microRNA expression in peripheral blood mononuclear cells from
      Graves' disease patients.
AB  - CONTEXT: Graves' disease (GD) is a common autoimmune disease that affects the
      thyroid gland. As a new class of modulators of gene expression, microRNA (miRNA)
      have been reported to play a vital role in immune functions and in the
      development of autoimmunity and autoimmune disease. OBJECTIVE: This study sought
      to characterize the different miRNA expression in peripheral blood mononuclear
      cells (PBMC) from GD patients and healthy individuals and examine their direct
      responses to T(3) treatment. METHODS: Forty-one patients who met criteria for
      initial GD, 13 GD patients in remission, and 35 healthy controls were recruited.
      Microarray was used to analyze the expression patterns of miRNA in PBMC obtained
      from initial GD patients and healthy controls. Three top-ranked miRNA were
      selected and validated by TaqMan-based real-time PCR in healthy controls, initial
      GD patients, and GD patients in remission. Furthermore, we cultured PBMC from
      healthy donors with or without T(3) treatment to examine direct effects of T(3)
      on selective miRNA. RESULTS: There were sixteen miRNA expressed differently in
      PBMC from initial GD patients compared with normal subjects. Further analysis
      consistently showed that the expression of miR-154*, miR-376b, and miR-431* were
      suppressed in PBMC from initial GD patients. In addition, their expression levels
      were recovered in GD patients in remission. Meanwhile, T(3) treatment could
      directly inhibit the expression of these miRNA in cultured PBMC from healthy
      subjects. CONCLUSIONS: The present work revealed that differentially expressed
      miRNA were associated with GD and T(3) exposure, which might serve as novel
      biomarkers of GD and potential targets for GD treatment.

PMID- 22456619
TI  - Treatment of vitamin D insufficiency in children and adolescents with
      inflammatory bowel disease: a randomized clinical trial comparing three regimens.
AB  - CONTEXT: Vitamin D insufficiency [serum 25-hydroxyvitamin D (25OHD) concentration
      less than 20 ng/ml] is prevalent among children with inflammatory bowel disease
      (IBD), and its treatment has not been studied. OBJECTIVE: The aim of this study
      was to compare the efficacy and safety of three vitamin D repletion regimens.
      DESIGN AND SETTING: We conducted a randomized, controlled clinical trial from
      November 2007 to June 2010 at the Clinical and Translational Study Unit of
      Children's Hospital Boston. The study was not blinded to participants and
      investigators. PATIENTS: Eligibility criteria included diagnosis of IBD, age 5
      21, and serum 25OHD concentration below 20 ng/ml. Seventy-one patients enrolled,
      61 completed the trial, and two withdrew due to adverse events. INTERVENTION:
      Patients received orally for 6 wk: vitamin D(2), 2,000 IU daily (arm A, control);
      vitamin D(3), 2,000 IU daily (arm B); vitamin D(2), 50,000 IU weekly (arm C); and
      an age-appropriate calcium supplement. MAIN OUTCOME MEASURE: We measured the
      change in serum 25OHD concentration (Delta25OHD) (ng/ml). Secondary outcomes
      included change in serum intact PTH concentration (DeltaPTH) (pg/ml) and the
      adverse event occurrence rate. RESULTS: After 6 wk, Delta25OHD +/- se was: 9.3 +/
      1.8 (arm A); 16.4 +/- 2.0 (arm B); 25.4 +/- 2.5 (arm C); P (A vs. C) = 0.0004; P
      (A vs. B) = 0.03. DeltaPTH +/- SE was -5.6 +/- 5.5 (arm A); -0.1 +/- 4.2 (arm B);
      -4.4 +/- 3.9 (arm C); P = 0.57. No participant experienced hypercalcemia or
      hyperphosphatemia, and the prevalence of hypercalciuria did not differ among arms
      at follow-up. CONCLUSIONS: Oral doses of 2,000 IU vitamin D(3) daily and 50,000
      IU vitamin D(2) weekly for 6 wk are superior to 2,000 IU vitamin D(2) daily for 6
      wk in raising serum 25OHD concentration and are well-tolerated among children and
      adolescents with IBD. The change in serum PTH concentration did not differ among
      arms.

PMID- 22456621
TI  - Erythrocyte n-3 fatty acids and metabolic syndrome in middle-aged and older
      Chinese.
AB  - CONTEXT: Few studies examined associations of circulating n-3 fatty acid levels
      with metabolic syndrome (MetS) among Chinese populations who have low consumption
      of these fatty acids and high risk of developing MetS. OBJECTIVE: The objective
      of the study was to determine associations between erythrocyte n-3 fatty acids
      and MetS as well as its components among middle-aged and older Chinese men and
      women. DESIGN AND PARTICIPANTS: Erythrocyte levels of docosahexaenoic acid (DHA),
      docosapentaenoic acid, eicosapentaenoic acid, and alpha-linolenic acid (ALA) were
      measured by gas chromatography among 2754 participants aged 50-70 yr living in
      Beijing and Shanghai. MetS was defined using the updated National Cholesterol
      Education Program Adult Treatment Panel III criteria for Asian-Americans.
      RESULTS: After multivariable adjustment, higher levels of DHA, but neither
      eicosapentaenoic acid nor docosapentaenoic acid, were associated with lower odds
      of MetS as well as elevated blood pressure and triglycerides. Comparing extreme
      quartiles of DHA, odds ratios (95% confidence interval) were 0.75 (0.55, 1.01; P
      for trend = 0.04) for MetS; 0.70 (0.53, 0.92; P for trend = 0.01) for elevated
      blood pressure; and 0.64 (0.48, 0.87; P for trend = 0.005) for elevated
      triglycerides. In contrast, ALA concentrations were positively associated with
      MetS odds (odds ratio 4.06; 95% confidence interval 2.85, 5.80; P for trend
      <0.001). CONCLUSIONS: Higher concentrations of erythrocyte DHA were associated
      with lower odds of MetS, whereas higher concentrations of ALA were associated
      with increased odds among middle-aged and older Chinese. These findings warrant
      replication in other populations.

PMID- 22456622
TI  - Possible role of adrenomedullin in the pathogenesis of tubal ectopic pregnancy.
AB  - CONTEXT: Tubal ectopic pregnancy (tEP) is currently the leading cause of
      pregnancy-related deaths during the first trimester. Our current knowledge on the
      molecular pathogenesis is limited. OBJECTIVE: The objective of the study was to
      find out the possible role of adrenomedullin (ADM) in the pathogenesis of tEP.
      DESIGN: This was an experimental in vitro study on oviductal tissue. SETTING: The
      study was conducted at a university teaching hospital. PATIENTS AND
      INTERVENTIONS: Patients included those having oviducts removed surgically during
      salpingectomy for tEP or hysterectomy for benign gynecological conditions.
      Oviductal tissues were incubated in hormonal condition mimicking early pregnancy
      before used for in vitro experiments. MAIN OUTCOME MEASURES: Plasma ADM
      concentration, oviductal expression of ADM and its receptors, ciliary beat
      frequency, smooth muscle contraction were measured. RESULTS: The ciliary beat
      frequency and frequency of muscle contraction were lower in the oviducts from
      patients with tEP than those from simulated normal pregnancy. The plasma and
      oviductal tissue ADM levels were also lower. The decreases in ciliary beat and
      frequency of contraction were restored to normal after ADM treatment.
      CONCLUSIONS: The results suggest that the lower ADM level in the oviducts of tEP
      may lead to the decrease in ciliary beating and muscle contraction, with the
      result that the embryo is retained and implanted in the oviduct. Our findings
      explain for the first time the etiology of tubal pregnancy on the basis of an
      impairment of the transport of the fertilized ovum resulting from an ADM
      deficiency and raise the possibility of using the plasma ADM level as a predictor
      for tubal ectopic pregnancy.

PMID- 22456623
TI  - A high prevalence of dual thyroid ectopy in congenital hypothyroidism: evidence
      for insufficient signaling gradients during embryonic thyroid migration or for
      the polyclonal nature of the thyroid gland?
AB  - BACKGROUND: Thyroid ectopy results from the failure of the thyroid precursor
      cells to migrate from the primordial pharynx to the anterior part of the neck.
      Most ectopic thyroids are revealed by congenital hypothyroidism and present as a
      single round mass at the base of the tongue, with no other thyroid tissue.
      However, some cases have dual ectopy, with part of the tissue having partially
      migrated. We hypothesized that this occurs more frequently than previously
      reported. METHODS: To determine the prevalence of dual ectopy, we reviewed the
      pertechnetate scintigraphies of 81 patients with congenital hypothyroidism from
      thyroid ectopy diagnosed between 2002 and 2011 at our institution. RESULTS: We
      report a series of seven cases (9%) of dual ectopy, representing an incidence
      ranging from 1:50,000 to 1:70,000. CONCLUSIONS: Almost one in 10 cases with
      congenital hypothyroidism due to thyroid ectopy has dual ectopy. This suggests
      that two populations of cells diverged at an early stage of development, which
      may arise from insufficient signaling gradients in surrounding tissues during
      early organogenesis or may indirectly support the polyclonal nature of the
      thyroid.

PMID- 22456625
TI  - MiR-125 in normal and malignant hematopoiesis.
AB  - MiR-125 is a highly conserved microRNA throughout many different species from
      nematode to humans. In humans, there are three homologs (hsa-miR-125b-1, hsa-miR
      125b-2 and hsa-miR-125a). Here we review a recent research on the role of miR-125
      in normal and malignant hematopoietic cells. Its high expression in hematopoietic
      stem cells (HSCs) enhances self-renewal and survival. Its expression in specific
      subtypes of myeloid and lymphoid leukemias provides resistance to apoptosis and
      blocks further differentiation. A direct oncogenic role in the hematopoietic
      system has recently been demonstrated by several mouse models. Targets of miR
      125b include key proteins regulating apoptosis, innate immunity, inflammation and
      hematopoietic differentiation.

PMID- 22456624
TI  - Bowel preparation with polyethylene glycol electrolyte solution: optimizing the
      splitting regimen.
AB  - AIM: Quality of bowel cleansing significantly increases the shorter the time
      between bowel solution intake and endoscopic examination. We tested the efficacy
      and patient tolerability following a modified polyethylene glycol electrolyte
      (PEG) splitting regimen. METHODS: This was a prospective, single-blind,
      randomized, study. Patients were assigned to receive either PEG 4 L the afternoon
      before colonoscopy or PEG 3 L the day before and 1 L 3h before the procedure the
      day of colonoscopy. RESULTS: The study population consisted of 336 patients,
      including 168 participants in each study arm. Although the bowel preparation
      quality was similarly quoted as excellent/good following the split and full
      regimen (95.2% vs 92.8%; p=0.3), a significant (p<0.0001) shift from good towards
      an excellent preparation (26.8% vs 68.4%) was observed following the split
      regimen as compared to the full regimen (55.4% vs 37.5%). The incidence of side
      effects did not differ. When patients were asked about a future preparation if
      needed, 69% and 31% following the split and full regimen, respectively, declared
      to accept again the same preparation, the difference being statistically
      significant (p<0.001). CONCLUSIONS: Our data found that an excellent bowel
      cleansing could be frequently achieved by simply modifying the split regimen from
      the standard PEG 2 plus 2 L to 3 plus 1 L.

PMID- 22456626
TI  - Common genetic variation contributes significantly to the risk of childhood B
      cell precursor acute lymphoblastic leukemia.
AB  - Recent genome-wide association studies (GWAS) have provided the first unambiguous
      evidence that common genetic variation influences the risk of childhood B-cell
      precursor acute lymphoblastic leukemia (BCP-ALL), identifying risk single
      nucleotide polymorphisms (SNPs) localizing to 7p12.2, 9p21.3, 10q21.2 and
      14q11.2. The testing of SNPs individually for an association in GWA studies
      necessitates the imposition of a very stringent P-value to address the issue of
      multiple testing. While this reduces false positives, real associations may be
      missed and therefore any estimate of the total heritability will be negatively
      biased. Using GWAS data on 823 BCP-ALL cases by considering all typed SNPs
      simultaneously, we have calculated that 24% of the total variation in BCP-ALL
      risk is accounted for common genetic variation (95% confidence interval 6-42%).
      Our findings provide support for a polygenic basis for susceptibility to BCP-ALL
      and have wider implications for future searches for novel disease-causing risk
      variants.

PMID- 22456627
TI  - Folding-promoted TBAX-mediated selective demethylation of methoxybenzene-based
      macrocyclic aromatic pentamers.
AB  - Described in this study is the ability of tetrabutylammonium salts (TBAX) to
      mediate an efficient mono- or di-demethylation removing one or two out of five
      aromatic methoxy methyl groups situated in similar chemical microenvironments in
      a H-bonded macrocyclic aromatic pentamer. These demethylations are found to be
      both chemo- and regioselective, and promoted by the H-bonding directed folding of
      the macrocyclic backbone.

PMID- 22456628
TI  - Adaptation dynamics of Clostridium butyricum in high 1,3-propanediol content
      media.
AB  - Aim of the present study was to evaluate the effect of exogenous additions of 1,3
      propanediol (1,3-PDO) on microbial growth and metabolites production of
      Clostridium butyricum VPI 1718 strain, during crude glycerol fermentation.
      Preliminary batch cultures in anaerobic Duran bottles revealed that early
      addition of 1,3-PDO caused growth cessation in rather low quantities (15 g/L),
      while 1,3-PDO additions during the middle exponential growth phase up to 70 g/L
      resulted in an almost linear decrease of the specific growth rate (MU),
      accompanied by reduced glycerol assimilation, with substrate consumption being
      used mainly for energy of maintenance requirements. During batch trials in a 3-L
      bioreactor, the strain proved able to withstand more than 70 g/L of both
      biologically produced and externally added 1,3-PDO, whereas glycerol assimilation
      and metabolite production were carried on at a lower rate. Adaptation of the
      strain in high 1,3-PDO concentration environments was validated during its
      continuous cultivation with pulses of 1,3-PDO in concentrations of 31 and 46 g/L,
      where no washout phenomena were noticed. As far as C. butyricum cellular lipids
      were concerned, during batch bioreactor cultivations, 1,3-PDO addition was found
      to favor the biosynthesis of unsaturated fatty acids. Also, fatty acid
      composition was studied during continuous cultures, in which additions of 1,3-PDO
      were performed at steady states. Lipids were globally more saturated compared to
      batch cultures, while by monitoring of the transitory phases, it was noticed that
      the gradual diol washout had an evident impact in the alteration of the fatty
      acid composition, by rendering them more unsaturated.

PMID- 22456629
TI  - Chiari III malformation with proatlas abnormality.
AB  - Chiari III malformations are extremely rare hindbrain malformations that are
      associated with a high early mortality rate, or severe neurologic deficits in the
      survivors. They are characterized by an occipital or cervical encephalocele,
      along with anomalies commonly seen with the type II malformation. Chiari III in
      association with proatlas abnormality is very rare. Here we describe a patient
      with Chiari III malformation associated with occipital condyle hypoplasia.

PMID- 22456630
TI  - Influence of lattice integrity and phase composition on the photocatalytic
      hydrogen production efficiency of ZnS nanomaterials.
AB  - Ambient S annealing was adopted to regulate the crystallinity of a ZnS
      microsphere, which resulted in a significant improvement in the photocatalytic
      hydrogen production activity (PHPA). Moreover, with S ambient treatment, wurtzite
      ZnS showed better PHPA than sphalerite ZnS, possibly because the inter-polar
      electric field of the wurtzite phase could promote the separation of photo
      excited electron-hole pairs.

PMID- 22456631
TI  - Injectable gels for tissue/organ repair.

PMID- 22456632
TI  - Limited effects of a 2-year school-based physical activity intervention on body
      composition and cardiorespiratory fitness in 7-year-old children.
AB  - The aim of this study was to assess the effects of a 2-year cluster-randomized
      physical activity and dietary intervention program among 7-year-old (at baseline)
      elementary school participants on body composition and objectively measured
      cardiorespiratory fitness. Three pairs of schools were selected and matched, then
      randomly selected as either an intervention (n = 151) or control school (n =
      170). None of the effect sizes of body composition were statistically
      significant. Children in the intervention group increased their fitness by an
      average of 0.37 z score units more than the controls (95% CI:-0.27 to 1.01, P =
      0.18), representing an improvement of 0.286 W/kg. Boys had higher fitness
      (mean(diff) = 0.35 z scores, 95% CI: 0.13-0.58, P = 0.001) than girls,
      independent of study group, fitness z score at baseline and body mass index. Post
      hoc analysis showed that the intervention school with the highest fitness z score
      change was significantly different from two of the lowest control schools
      (mean(diff) = 0.83 z scores, 95% CI: 0.44-1.21, P < 0.0001 and mean(diff) = 0.70
      z scores, 95% CI: 0.29-1.10, P = 0.01), but it was also significantly different
      from the lowest intervention school (mean(diff) = 0.59 z scores, 95% CI: 0.19
      0.99, P = 0.05). The results of this intervention are inconclusive as regards to
      the effects on fitness, but the intervention did not have any statistically
      significant effect on body composition.

PMID- 22456633
TI  - Pulmonary vascular resistance in repaired congenital diaphragmatic hernia vs. age
      matched controls.
AB  - INTRODUCTION: Infants and children with repaired congenital diaphragmatic hernia
      (CDH) often continue to show delayed growth and development that may be, in part,
      secondary to unrecognized persistence of increased pulmonary vascular resistance
      (PVR). METHODS: Data were reviewed from all patients ages 6-36 mo with repaired
      CDH who underwent cardiac catheterization from 2007 to 2010 and were compared to
      data from a control population of patients undergoing percutaneous closure of a
      patent ductus arteriosus (PDA). Indexed pulmonary blood flow (Qp), mean pulmonary
      artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and PVR were
      examined. RESULTS: Data from 8 CDH patients and 10 control patients were
      examined. The mPAP (22.5 +/- 3.33 vs. 18.2 +/- 4.13 mm Hg) and PVR (3.66 +/- 0.79
      vs. 1.22 +/- 0.4 iwU (indexed Wood's units)) were both significantly elevated in
      the CDH population, whereas the Qp (4.08 +/- 1.43 vs. 6.82 +/- 1.46 l/min/m(2))
      was significantly lower in this population. There was no significant difference
      in pulmonary capillary wedge pressure (PCWP). Less than half of the CDH patients
      had signs of pulmonary hypertension (PH) on echocardiogram. DISCUSSION: Our data
      suggest that children who are ages 6-36 mo with repaired CDH have significantly
      increased PVR compared with controls and early consideration of cardiac
      catheterization may be warranted.

PMID- 22456634
TI  - Left subclavian artery coverage during TEVAR: is revascularization necessary?
AB  - Thoracic endovascular aortic repair (TEVAR) has rapidly become a viable and
      accepted treatment option for atherosclerotic aortic aneurysms as well as a
      variety of other aortic pathologies including ulcers, dissection, coarctation and
      disruption. Left subclavian artery (LSA) coverage is often necessary to achieve
      proximal seal in up to 40% of patients treated with TEVAR. The management of the
      LSA in this cohort of patients remains controversial. Studies in support of
      routine pre-operative LSA revascularization show that coverage of the LSA during
      TEVAR is associated with an increased risk of stroke, paraplegia and arm
      ischemia. Other studies show that intentional coverage of the LSA without
      revascularization is not associated with increased morbidity and lends support to
      those who advocate more selective LSA revascularization during TEVAR (i.e. in
      those patients with patent LIMA-coronary bypass, dominant or isolated left
      vertebral artery, or a functioning left upper extremity (LUE) dialysis
      arteriovenous fistula). This paper is intended to review the literature comparing
      routine and selective LSA revascularization after TEVAR to determine the best
      management strategy.

PMID- 22456635
TI  - Unusual inflow sources and device introduction sites in aortic arch debranching.
AB  - AIM: Aim of the study was to evaluate a single center experience on hybrid
      treatment for thoracic aortic diseases, including aortic arch and ascending aorta
      endografting needing a total debranching from descending thoracic aorta and an
      antegrade endograft deployment from left ventricle. METHODS: Between January 2004
      and December 2010 48 patients underwent thoracic aorta endografting, with
      coverage of at least one supra-aortic artery, because of atherosclerotic,
      dissecting and post-traumatic aneurysms or complications of previous aortic
      surgery. Supra-aortic trunks revascularization was obtained from ascending aorta,
      common carotid arteries and, in three cases, from descending thoracic aorta since
      the unavailability of common inflow sites. In three cases the antegrade endograft
      introduction through left ventricle (transapical approach, 2 cases) or ascending
      aorta (one case) was the only possibility for a safe deployment. RESULTS: Three
      groups have been identified on the basis of the proximal landing zone. Group A
      (27 patients): zone 2; Group B (9 patients): zone 1; Group C (12 patients): zone
      0. The 30 days mortality was respectively 7.4%, 0% and 16%. Post operative
      paraplegia occurred in the 7.4% of group A, respiratory insufficiency and
      infections were the main post-operative complications with an incidence reaching
      30% in each group. CONCLUSION: Hybrid procedures on aortic arch represent a
      possible treatment for cases unfit for open surgery despite the complication
      rates and mortality are not negligible. In selected cases, the endografting can
      be extended up to beyond the landing zone 0 where an antegrade transventricular
      endograft deployment and a supra-aortic perfusion from descending thoracic aorta
      represent a feasible option.

PMID- 22456636
TI  - Zenith TX2LowProfile TAA Endovascular Graft: a next generation thoracic stent
      graft.
AB  - AIM: The aim of the present article is to describe a new thoracic stent graft
      (Zenith TX2 Low-Profile TAA Endovascular Graft). METHODS: Feasibility of
      endovascular repair of thoracic aortic aneurysms depends on several anatomic
      factors. A primary limitation is an adequate arterial approach. Since most
      currently used endografts require large introducer sheaths, patients with
      severely diseased iliofemoral vessels are often excluded from this less-invasive
      technique. Attempts to overcome access difficulties increase the risk for
      arterial access-site complications such as aortoiliac rupture. In addition,
      highly angulated proximal landing zones provide challenges in obtaining proximal
      graft conformance and sealing. RESULTS: The introduction of next-generation
      endografts such as the Zenith TX2LowProfile TAA Endovascular Graft provides a
      solution for a larger number of patients, including those with small vessels,
      vascular access problems and tortuous aortic anatomy. CONCLUSION: The ongoing
      Zenith TX2 Low-Profile Endovascular Graft trial will build further understanding
      of the performance of the device allowing for treatment of a wider patient
      population.

PMID- 22456638
TI  - New C-TAG device and overcome of compression events.
AB  - This article describes the modifications made to the TAG thoracic device (WL
      Gore, Flagstaff, AZ, USA) to better accommodate to anatomies seen in young trauma
      patients and patients with dissections. The device was initially approved and
      tested for degenerative thoracic aneurysms. The newer conformable-TAG (cTAG) is
      better able to accommodate to tight aortic arches and smaller aortic diameter
      with circumferential aortic wall opposition.

PMID- 22456637
TI  - Influence of clinical presentation on the outcome of acute B aortic dissection:
      evidences from IRAD.
AB  - AIM: In-hospital outcome of acute type B dissection (ABAD) is strongly related to
      preoperative aortic conditions. In order to clarify the influence of the clinical
      presentation on the outcome, we analyzed the patients of the International
      Registry of Acute Aortic Dissection (IRAD). All patients affected by complicated
      ABAD, enrolled in the IRAD from 1996-2004, were included. Complications were
      defined as the presence of shock, periaortic hematoma, spinal cord ischemia,
      preoperative mesenteric ischemia/infarction, acute renal failure, limb ischemia,
      recurrent pain, refractory pain or refractory hypertension (group I). All other
      patients were categorized as uncomplicated (group II). A comprehensive analysis
      was performed of all clinical variables in relation to in-hospital outcome.
      RESULTS: The overall in-hospital mortality among 550 patients was 12.4%.
      Mortality in group I (250 patients) was 20.0 %, compared to 6.1% in group II (300
      patients) (P<0.001). Univariate predictors of ABAD complications were Marfan
      syndrome, abrupt onset of pain, migrating pain, any focal neurological deficits,
      need for higher number of diagnostic examinations and use of magnetic resonance
      and/or aortogram, abdominal vessels involvement at aortogram, larger descending
      aortic diameter, especially >6 cm, pleural effusion, and widened mediastinum on
      chest X-ray. Univariate predictors of a non complicated status were normal chest
      X-ray and medical management. In group I, in-hospital mortality following
      surgical and endovascular intervention were 28.6% and 10.1% (P=0.006),
      respectively. Independent predictors of overall in-hospital mortality included
      age >70 years, female gender, ECG showing ischemia, preoperative acute renal
      failure, preoperative limb ischemia, periaortic hematoma, and surgical
      management. The only independent variable protective for mortality was magnetic
      resonance as diagnostic test. CONCLUSION: ABAD is a heterogeneous disease that
      produces dissimilar clinical subsets, each of which can have specific clinical
      signs, management and in-hospital results. In IRAD ABAD uncomplicated patients,
      medical therapy was associated with best hospital outcome, while endovascular
      interventions were associated with better results than surgery when invasive
      treatments were required. Although selection bias may be possible, and
      irrespective of treatments, knowledge of significant risk factors for mortality
      may contribute to a better management and a more defined risk-assessment in
      patients affected by ABAD.

PMID- 22456639
TI  - When is embolic protection needed in lower extremity interventions and how should
      it be done.
AB  - Distal embolization (DE) during lower extremity arterial intervention is a
      potentially devastating complication which could lead to limb loss. The use of a
      distal embolic protection device (EP) may prevent significant DE during
      intervention. Studies investigating the incidence and impact of DE suggest that
      it is a rare event with low impact on clinical outcomes. The use of EP during
      peripheral interventions has only been studied in uncontrolled small series with
      no comparison to unprotected interventions. In spite of the absence of good
      quality studies, there may be situations where EP is helpful. These situations
      may be when lesions or devices are particularly prone to produce emboli. The EP
      device may produce its own serious complications which must be considered prior
      to their use. In addition these devices are fairly expensive, a factor that needs
      to be considered when deciding to employ EP. A simple direct comparison of EP vs.
      no EP during lower extremity intervention could answer many clinical questions
      surrounding this controversy.

PMID- 22456640
TI  - Treatment of femoropopliteal stenoses and occlusions with mechanical rotational
      catheters: comparison of results with the Rotarex and Pathway devices.
AB  - AIM: For the treatment of chronic lesions, various ablative procedures have been
      developed with the aim of improving the outcome of percutaneous transluminal
      angioplasty (PTA)/stent and/or reducing the length and number of implanted stents
      by removing stenotic or occlusive material. The objective of this study was to
      compare two mechanical rotational catheters (Rotarex and Pathway) with regard to
      their safety and effectiveness in the treatment of stenoses and occlusions of the
      femoropopliteal arteries. METHODS: A total of 156 patients with chronic stenoses
      or occlusions of the femoropopliteal vasculature were treated, 114 of them with
      the Rotarex catheter and 42 with the Pathway catheter. The pre-interventional
      Rutherford classification was on average 3.32 (2-5) in the Rotarex group and 2.93
      (2-5) in the Pathway group. The mean lesion length was 13.9 cm (2-30 cm) and 5.1
      cm (1-10 cm), respectively (P<0.05). The Ankle-Brachial Index (ABI) was
      determined pre- and postinterventionally and after 12 months. Colour-coded duplex
      ultrasound was additionally performed as a follow-up. RESULTS: The technical
      success rate was 98.2 % in the Rotarex group and 97.6% in the Pathway group. In
      the Rotarex group, additional balloon dilatation was performed in 75 patients
      (65.8%) and stent implantation was necessary in 12 patients (10.5%). In the
      Pathway group, 27 patients (64.3%) underwent additional balloon dilatation and 5
      (11.9%) stent implantation. Clinically, there was an increase in the ankle
      brachial index from 0.59 to 0.84 +/- 0.15 postinterventionally and 0.80 +/- 0.16
      12 months after Rotarex treatment, compared with an increase from 0.62 +/- 0.14
      to 0.84 +/- 0.15 postinterventionally and 0.81 +/- 0.12 12 months after Pathway
      treatment. In addition, there was a reduction in the Rutherford stage to 1.73 (1
      3) and 1.43 (1-3), respectively. During the follow-up period, 21 (21.4%)
      restenoses occurred in the Rotarex group and 8 (19.0%) in the Pathway group. Peri
      interventional complications included 7 dissections (4 after Rotarex, 3 after
      Pathway). Two distal embolisations were observed (both after Pathway). Throughout
      the entire duration of the study there were no amputations or fatalities.
      CONCLUSION: The atherectomy of lesions of the femoropopliteal arteries using the
      Rotarex and Pathway systems is safe. The low stent rate peri-interventionally and
      the low restenosis rate after 12 months, with a significantly longer lesion
      length, indicate a better effectiveness of the Rotarex system as a whole.

PMID- 22456642
TI  - Does below-the-knee placement of drug-eluting stents improve clinical outcomes?
AB  - Modern critical limb ischemia management algorithms endorse an "endovascular
      first" strategy of treatment. The advent of stents coated with anti-restenotic
      agents that are gradually eluted to the vessel wall has revolutionized modern
      endovascular therapies. Several single-center, non-randomized cohort series have
      provided compelling data about the short- to mid-term safety and effectiveness of
      drug-eluting stents in below-the-knee lesions and have fuelled further large
      scale research. Three multicenter randomized trials (the YUKON-BTX, the DESTINY
      and the ACHILLES trials) are now available and have paved the way for level I-A
      evidence about infrapopliteal use of drug-eluting stents. Amassed evidence
      strongly supports the use of olimus-eluting metal stents for focal obstructive
      infrapopliteal lesions in order to inhibit restenosis, prolong vessel patency and
      thereby achieve sustained patient improvement, as reflected by the significantly
      improved Rutherford-Becker classification, reduced number of repeat procedures
      and a trend towards improved wound healing. The present overview outlines current
      evidence about clinical outcomes after below-the-knee drug-eluting stent
      placement compared to more traditional endovascular treatments like conventional
      old balloon angioplasty and bare metal stents. Available evidence is appraised in
      the context of clinically meaningful results and relevant unresolved issues are
      highlighted.

PMID- 22456641
TI  - Results from an Italian multicentric registry comparing heparin-bonded ePTFE
      graft and autologous saphenous vein in below-knee femoro-popliteal bypasses.
AB  - AIM: The aim of this study was to evaluate early and follow-up results of below
      knee bypasses performed with a bioactive heparin-treated ePTFE graft in patients
      with peripheral arterial obstructive disease (PAOD) in a multicentric
      retrospective registry involving seven Italian vascular centers and to compare
      them with those obtained in patients operated on with autologous saphenous vein
      (ASV) in the same centres in the same period of time. METHODS: Over a nine-year
      period, ending in 2010, a heparin bonded prosthetic graft (Propaten Gore-Tex,
      W.L. Gore & Associates Inc, Flagstaff, AZ, USA) was implanted in 556 patients
      undergoing below-knee revascularization for PAOD (HePTFE group). In the same
      period of time 394 below-knee bypasses with ipsilateral ASV were performed (ASV
      group). Data concerning these interventions were retrospectively collected in a
      multicenter registry with a dedicated database. Early (<30 days) results were
      analyzed in terms of graft patency, major amputation rates and mortality. Follow
      up results were analyzed in terms of primary and secondary graft patency, limb
      salvage and survival. RESULTS: Among patients of HePTFE group, 413 had critical
      limb ischemia (74%); the corresponding figure for ASV group was 84% (332
      interventions, P<0.001). Eighty-nine patients in HePTFE group (16%) and 207
      patients in ASV group (52.5%; P<0.001) had distal tibial anastomosis. Patients in
      HePTFE group had more frequently adjunctive procedures performed at distal
      anastomotic sites in order to improve run-off status. Thirty-day death rate was
      1.9% in HePTFE group and 0.5% in ASV group (P=0.08). The rates of perioperative
      thromboses and amputations were 6% and 3.5% in HePTFE group, and 5% and 1.7% in
      ASV group, without significant differences between the two groups. Mean duration
      of follow-up was 28.5+/-22.1 months; 921 patients (97%) had at least one
      postoperative clinical and ultrasonographic control. Estimated 48-month survival
      rates were 81% in HePTFE group and 74% in ASV group (P=0.7, log rank 0.1).
      Primary patency rate at 48 months was significantly better in ASV group (61%)
      than in HePTFE group (44.5%; P=0.004, log rank 8.1). The rates of secondary
      patency at 48 months were 57% in HePTFE group and 67.5% in ASV group (P=0.1, log
      rank 1.9); the corresponding values in terms of limb salvage in patients with
      critical limb ischemia were 77% and 79.5% (P=0.3, log rank 0.9), respectively.
      CONCLUSION: Data from this large, retrospective registry confirmed that the
      indexed heparin-bonded ePTFE graft provides satisfactory early and mid-term
      results in patients undergoing surgical below-knee revascularization. While
      autologous saphenous vein maintains its superiority in terms of primary patency,
      secondary patency and limb salvage rates are comparable.

PMID- 22456643
TI  - Advances in below-the-knee drug-eluting balloons.
AB  - The management of critical limb ischemia due to below-the-knee disease remains
      challenging due to the frequent patient comorbidities, diffuse vascular
      involvement, and high rates of restenosis and disease progression. The BASIL
      study has established the substantial equivalence between bypass surgery and
      percutaneous transluminal angioplasty in this setting, at least at mid-term
      follow-up, but percutaneous techniques and devices have seen major developments
      since the publication of this pivotal trial in 2005. A major breakthrough has
      indeed been the introduction of drug-eluting balloons, which have several
      theoretical advantages in comparison to standard balloons and metallic stents for
      infra-popliteal lesions. Two clinical trials have already been reported with
      favorable results for the In.Pact Amphirion paclitaxel-eluting balloon, when
      employed for below-the-knee lesions. We hereby discuss the rationale for the use
      of drug-eluting balloons in this complex setting and the main findings of the
      study by Schmidt et al. and the DEBATE-BTK trial.

PMID- 22456644
TI  - Endovascular treatment of in-stent restenosis using excimer laser angioplasty and
      drug eluting balloons.
AB  - In-stent restenosis after endovascular treatment of stenotic and occlusive
      disease of the infrainguinal arteries is still a clinical challenge. In this
      paper an overview of the current status of drug-eluting balloon technology and
      results of clinical trials with drug-eluting balloon angioplasty is given.
      Furthermore a case series of 10 patients with in-stent restenosis that were
      treated with excimer laser angioplasty and drug eluting balloons is described. In
      this case series the mean lesion length treated was 115 mm, and the mean time to
      occurrence of restenosis after initial treatment was 7.2 months. At a mean follow
      up (of all patients) of 7.6 months no target vessel revascularization was seen.
      In 7 patients that had Duplex and/or angiographic control (mean follow-up 7
      months) no signs of neointimal hyperplasia were demonstrated. These short-term
      data compare favorable to results obtained with standard balloon angioplasty and
      cutting-balloon angioplasty. Long-term follow-up is necessary to define the role
      of combined excimer laser and drug-eluting balloon angioplasty in the treatment
      of in-stent restenosis further.

PMID- 22456645
TI  - In lower extremity PTAs intraluminal is better than subintimal.
AB  - With subintimal recanalization, a channel is deliberately created by dissecting
      the vessel wall in order to replace the native occluded lumen. This is opposed to
      intraluminal recanalization, where passage of an arterial obstructive lesion is
      performed by central luminal navigation. Both intraluminal and subintimal
      treatment has its proponents and adversaries. The appreciation of an investigator
      for a certain technique is commonly related to the training received and the
      personal experience. Yet, the intraluminal technique uses the clinically
      preferred route for adjunctive treatment, such as balloon angioplasty or stent
      deployment. A wide variety of devices designed to obtain intraluminal lesion
      passage is available and is currently being used in vascular centers worldwide.
      With intraluminal techniques, success rates of up to 95% have been reported.

PMID- 22456646
TI  - Siena EVAR Score.
AB  - AIM: Although several randomized trial and monocentric study reported good
      results EVAR of abdominal aortic aneurysm (AAA), the long-term results of EVAR is
      still debated for the incidence of complication and the necessity of
      reintervention and or surgical conversion. The aim of the present study was to
      generate a score to grade the risk of reintervention/conversion after EVAR.
      METHODS: We present a five-year prospective study. All patients with AAA and
      treated by EVAR were inserted in the study. Patients with ruptured AAA or treated
      with fenestrated-graft or chimney technique were excluded from the analysis. The
      rates of reintervention, surgical conversion and aneurysm-related death were
      recorded at 6 months after the procedure. Complication predictors were analyzed
      and was generated a numeric score for all the variables to predict the patient
      individual risk. RESULTS: During the study period 976 EVAR procedures were
      successfully performed. No patients were lost during follow-up. We report 23
      reinterventions (2.35%), the majority were performed electively. In six cases
      (0.61%) was performed conversion to surgical repair (1 graft infection, 3 for
      continuous growing of the aneurysmal sac and 2 cases for a ruptured AAA). In our
      experience, we report 4 deaths (0.4%) due to aneurysm rupture (1 case), acute
      myocardial infarction (2 cases) and colon cancer (1 case). The procedures were
      defined at low, moderate or high risk, respectively, according to whether the
      Siena EVAR Score was defined as EVAR1 (score <3), EVAR2 (3-6) or EVAR3 (>6).
      CONCLUSION: Our Score could be an useful tool to predict patients individual risk
      after EVAR but, to be validated, needs to be analyzed in independents cohorts in
      different Center.

PMID- 22456647
TI  - Early and mid-term results of total laparoscopic bypass for aortoiliac occlusive
      lesions.
AB  - AIM: The aim of this study was to investigate the early and mid term results of
      total laparoscopic bypass for aortoiliac occlusive lesions. METHODS: From
      December 2001 to January 2007, we performed 32 laparoscopic bypasses for
      aortoiliac lesions. The mean age was 52.9 years. Clinical stages included: severe
      intermittent claudication (N.=24) ischemic rest pain (N.=5) and tissue loss or
      gangrene (N.=3). According to the TASC classification, the lesions were type B in
      three cases, C in nine cases and D in 20 cases. Graft patency was controlled by
      means of duplex scan before discharge and during the follow-up. The patency rates
      were calculated using Kaplan-Meier analysis. RESULTS: In 27 out of 32 patients
      the total laparoscopic bypass was successful (84%). Conversion was necessary in
      five patients. The mean operative time was 338 minutes (range, 200-620 minutes),
      the mean aortic clamping time was 73 minutes (range, 35-144 minutes). Mortality
      was 0%. The postoperative course was uneventful in 19 patients (70%). The mean
      follow-up was 32.1 months. In this period we had two deaths, one from breast
      cancer after 12 months. The second patient has committed suicide after 48 months.
      Two graft occlusions occurred at 3 and 21 months. No other late complications
      were observed. The primary and secondary graft patency rate was estimated by
      Kaplan-Meier analysis at 92% and 96% on the first year and 87% and 93% at three
      years, respectively. CONCLUSION: Early and mid-term results of total laparoscopic
      bypass are good in selected patients and comparable to these of conventional
      surgery.

PMID- 22456648
TI  - Late spontaneous recanalization of a symptomatically occluded internal carotid
      artery two years after extra-intracranial bypass. Case report and review of the
      literature.
AB  - Spontaneous recanalization of the internal carotid artery (ICA) is rarely
      observed. Mainly case reports are published. Most often early recanalization
      occurs within days or weeks and only a few cases of late recanalization months or
      years after detected occlusion are reported. Symptomatic bilateral ICA occlusion
      is regarded as an acceptable indication for extra-intracranial (EC-IC) bypass.
      The authors report on a case with bilateral symptomatic ICA occlusion and EC-IC
      bypass >2 years prior to detected spontaneous leftsided recanalization.
      Spontaneous recanalization unmasking a high degree ICA stenosis at the carotid
      bifurcation allowed a successful subsequent surgical recanalization in this
      patients. Mechanisms of early and late recanalization as well as treatment
      options are discussed.

PMID- 22456649
TI  - Dual-Source computed tomography of the chest in the surgical planning of repeated
      cardiac surgery.
AB  - AIM: When reoperative cardiac surgery is indicated, detailed, three-dimensional
      imaging of the thorax permits accurate depiction of cardiac anatomy and vascular
      structures potentially increasing the safety of the surgical procedure. We sought
      to evaluate the contribution of dual-source multidetector-row computed tomography
      (DSCT) of the heart and thorax in planning repeated open heart surgery. METHODS:
      Twenty-eight patients (mean age, 68 years) scheduled for repeated cardiac surgery
      who had undergone previous coronary artery bypass grafting (n=19) or cardiac
      valve replacement (8) or combined valvular and bypass surgery (1) underwent
      contrast-enhanced ECG-gated DSCT (Somatom Definition, Siemens Medical Solutions)
      of the whole thorax with a temporal resolution of 82 ms and a spatial resolution
      of 0.4 mm3. The indication for repeated surgery was bypass surgery (N.=6), valve
      replacement (16), combined bypass and valvular surgery (5) or other reasons (1).
      Assessment of surgical risk based on DSCT data were performed in terms of the
      relation of the ascending aorta and cardiac structures to the expected median
      sternotomy line, graft patency and anatomic course, and the degree of
      calcification of the ascending aorta and coronary arteries. RESULTS: DSCT
      findings led to a change of surgical approach for 9/28 (32.1%) patients (non
      midline incision, N.=3; surgery performed under circulatory arrest, N.=5;
      peripheral arterial cannulation before sternotomy, N.=1) and cancellation of
      surgery for 4/28 (14.3%) patients (heavy aortic and coronary calcifications
      impeding bypass surgery, N.=2; right heart or aortic aneurysm in close proximity
      to the sternum in high risk patients, N.=2). The planned surgical approach
      remained unchanged after DSCT for the remaining15/28 (53.6%) patients. Of 54
      bypass graft conduits (20 arterial, 34 venous) visualized on DSCT in 20 patients
      after previous bypass grafting, 16 arterial and 24 venous grafts were patent,
      while 4 arterial and 10 venous grafts were occluded. CONCLUSION: DSCT of the
      heart and thorax is an effective, non-invasive tool for the preoperative planning
      of repeated cardiac surgery. The technique provides significant information to
      modify the surgical approach and may increase the safety of the procedure.

PMID- 22456650
TI  - Endoscopic versus open radial artery harvesting for coronary artery bypass
      grafting.
AB  - AIM: The radial artery has become the artery of choice after the internal
      thoracic artery for coronary artery bypass grafting (CABG). This study compares
      wound healing and arm complications after endoscopic versus open radial artery
      harvesting for CABG. METHODS: From January 2002 to July 2004, 509 patients
      underwent CABG in which a radial artery conduit was used. Thirty-nine had
      endoscopic and 470 had conventional open radial artery harvesting. A propensity
      score was used to obtain 1:3 matching of all endoscopic to 117 open-harvesting
      patients. Postoperative wound healing using the Hollander scale, local neurologic
      deficits, wound infection, and pain scores were compared. RESULTS: Wound healing:
      34 of 39 endoscopic wounds exhibited a perfect Hollander score versus 339 of 470
      open-harvest wounds (P=0.01). Wound appearance in particular was better than for
      open harvesting (P=0.004), with no abnormal step-off borders, irregular contours,
      or abnormal scar width observed. Neurologic deficits. Three incomplete neurologic
      deficits were observed after open harvesting (two being distal sensitivity
      localized in the interspace between the first and second metacarpals); one
      complete neurologic deficit occurred after endoscopic harvesting, but improved
      remarkably prior to hospital discharge. Wound infection. Occurrence of wound
      infection was similar in the two groups (P=0.7), although infection was more
      severe with open harvesting. Pain: pain score was lower (P=0.006) with endoscopic
      harvesting. CONCLUSION: Compared with conventional open harvesting, endoscopic
      radial artery harvesting was associated with better wound appearance and less
      pain. Occurrence of neurologic deficits and wound infection was infrequent in
      both groups.

PMID- 22456651
TI  - Anatomic repair of interrupted aortic arch in adult.

PMID- 22456652
TI  - Popliteal artery pseudoaneurysms after total knee arthroplasty.

PMID- 22456653
TI  - Percutaneous closure of iatrogenic atrial septal defect due to implantation of a
      left-left "Tandem Heart" ventricle assistance device in a postcardiotomy cardiac
      failure: six-year follow-up.

PMID- 22456654
TI  - Minimally invasive right mini-thoracotomy for reoperative mitral valve
      replacement after deep sternal wound infection.

PMID- 22456655
TI  - Do lifestyle choices explain the effect of alcohol on bone mineral density in
      women around menopause?
AB  - BACKGROUND: Moderate alcohol consumption has been shown to be positively
      associated with increased bone mineral density (BMD). However, other lifestyle
      choices have also been shown to have an effect on bone health. OBJECTIVE: The
      objective was to examine the association between alcohol intake and BMD in women
      around menopause in the United Kingdom and to determine whether any association
      is independent of other lifestyle choices. DESIGN: A cross-sectional study design
      was used to examine the relation between alcohol intake and BMD in a cohort of
      3218 women aged 50-62 y from the Aberdeen Prospective Osteoporosis Screening
      Study. Women were grouped into clusters according to their lifestyle choices.
      ANCOVA was used to examine the effect of categorized alcohol intake on BMD
      adjusted for cluster of lifestyle and other baseline covariates. The ANCOVA was
      repeated for different types of alcoholic beverage (eg, beer, liquor, and wine)
      separately. RESULTS: Three lifestyle clusters were identified and were based on
      different levels of the following 3 factors: smoking pack-years, fruit and
      vegetable intakes, and physical activity. In the lifestyle-adjusted models, women
      who consumed >1 drink/d of alcohol had a significantly greater femoral neck BMD
      (P = 0.008) and lumbar spine BMD (P = 0.007) than did those who never consumed
      alcohol. For separate alcoholic drinks, only beer had a positive significant
      effect on lumbar spine BMD after adjustment for lifestyle (P = 0.005).
      CONCLUSION: Moderate alcohol intake appears to be positively associated with BMD
      independently of the type of lifestyle led by women around menopause.

PMID- 22456656
TI  - Carbohydrate nutrition is associated with changes in the retinal vascular
      structure and branching pattern in children.
AB  - BACKGROUND: Higher intake of carbohydrates and high-glycemic index (high-GI)
      diets could lead to small vessel dysfunction. OBJECTIVES: We aimed to assess the
      associations between intakes of high-GI and high-glycemic load (high-GL) diets,
      carbohydrate, and the main carbohydrate-containing food groups and retinal
      microvascular changes in preadolescents. DESIGN: Students aged 12 y (n = 2353)
      from a random cluster sample of 21 schools underwent detailed eye examinations.
      Retinal vessel caliber and fractal dimension were measured from digital retinal
      images. A validated semiquantitative food-frequency questionnaire was
      administered. RESULTS: After multivariable adjustment, children who consumed soft
      drinks once or more per day had significantly narrower mean retinal arterioles
      (~1.9 MUm) than did those who never or rarely consumed soft drinks (P-trend =
      0.03). When the highest to lowest tertiles of carbohydrate consumption were
      compared, girls had significantly narrower retinal arterioles (~1.4 MUm; P-trend
      = 0.03) and boys had wider venules (~2.3 MUm; P-trend = 0.02). In girls only, a
      higher-GI diet was associated with narrower retinal arterioles (0.98-MUm
      narrowing of retinal arteriolar caliber per SD increase in GI, P = 0.01).
      Carbohydrate intake and a high-GL diet were associated with greater retinal
      fractal dimension in girls (highest compared with lowest tertiles: P-trend =
      0.003 and 0.01, respectively). CONCLUSIONS: Greater consumption of carbohydrates
      and soft drinks was associated with retinal arteriolar narrowing and venular
      widening. Because these microvascular signs have been shown to be markers of
      future cardiovascular disease risk, the presence of this risk factor in children
      could support the need for healthy dietary patterns that include lower
      consumption of high-GI foods and soft drinks.

PMID- 22456657
TI  - Breastfeeding after cesarean delivery: a systematic review and meta-analysis of
      world literature.
AB  - BACKGROUND: The rate of exclusive breastfeeding remains low in many countries.
      Furthermore, cesarean delivery (CD) is increasing and may affect breastfeeding
      success. OBJECTIVE: The objective was to conduct a systematic review and meta
      analysis of observational studies to determine whether CD (prelabor or in-labor)
      is associated with a lower rate of breastfeeding compared with vaginal delivery
      (VD). DESIGN: Studies published before January 2011 that reported breastfeeding
      up to 6 mo postpartum and compared outcomes after CD or VD, including foreign
      language publications, were identified through PubMed and bibliographic review.
      Prespecified data were extracted independently by multiple observers. The types
      of CD [prelabor (elective/scheduled) or in-labor (emergency)] were compared by
      subgroup analyses. Potential sources of study-level bias were analyzed by using
      meta-regression and sensitivity analyses. RESULTS: The systematic review included
      53 studies (554,568 subjects, 33 countries); 25 authors contributed additional
      data (245,455 subjects), and 48 studies (553,306 subjects, 31 countries) were
      included in the meta-analysis. Rates of early breastfeeding (any initiation or at
      hospital discharge) were lower after CD compared with after VD (pooled OR: 0.57;
      95% CI: 0.50, 0.64; P < 0.00001) and lower after prelabor but not after in-labor
      CD (prelabor OR: 0.83; 95% CI: 0.80, 0.86; P < 0.00001; in-labor OR: 1.00; 95%
      CI: 0.97, 1.04; P = 0.86). In mothers who initiated breastfeeding, CD had no
      significant effect on any breastfeeding at 6 mo (OR: 0.95; 95% CI: 0.89, 1.01; P
      = 0.08). CONCLUSIONS: There was a negative association between prelabor CD and
      early breastfeeding. If breastfeeding is initiated, mode of delivery has no
      apparent effect on the number of mothers still breastfeeding at 6 mo. Women and
      health care workers should be aware of the negative associations between CD and
      early breastfeeding and consequent implications for infants' well-being.

PMID- 22456658
TI  - Feeding behaviors of low-income mothers: directive control relates to a lower BMI
      in children, and a nondirective control relates to a healthier diet in
      preschoolers.
AB  - BACKGROUND: A topic of interest in the etiology of child obesity is whether and
      how parental feeding behaviors are associated with the food intake and weight
      status of children. OBJECTIVE: The objective was to explore whether and how
      directive (overt) and nondirective (covert and food environmental structure)
      types of parental feeding control were associated with children's food intake and
      weight status. DESIGN: This was a cross-sectional exploratory study using
      structural equation modeling to determine directional associations between
      maternal feeding practices and children's food intake and weight status.
      Researchers collected data from 330 dyads of children aged 3-5 y and mothers
      participating in a federal preschool program for low-income families (Head Start)
      in Michigan. The mothers' feeding practices (directive and nondirective control),
      the children's food intakes, and the height and weight of both the mothers and
      children were measured. Structural equation models tested the relations between
      maternal feeding practices, the children's food intake, and weight status.
      RESULTS: The structural equation model confirmed that children's weight status
      was inversely associated with mothers' directive control, and mothers'
      nondirective control was associated with children's intakes of more nutrient
      dense foods and less energy-dense foods. No association was found between the
      mothers' directive control and the children's food intakes. CONCLUSIONS: Mothers'
      use of nondirective feeding practices was associated with children's intakes of
      more nutrient-dense foods. However, use of more directive feeding control was
      associated with lower weight status in preschoolers of low-income mothers. These
      findings need to be examined in longitudinal studies. This trial was registered
      at clinicaltrials.gov as NCT01525186.

PMID- 22456659
TI  - Inverse association between brown adipose tissue activation and white adipose
      tissue accumulation in successfully treated pediatric malignancy.
AB  - BACKGROUND: Although the accumulation of white adipose tissue (WAT) is a risk
      factor for disease, brown adipose tissue (BAT) has been suggested to have a
      protective role against obesity. OBJECTIVE: We studied whether changes in BAT
      were related to changes in the amounts of subcutaneous adipose tissue (SAT) and
      visceral adipose tissue (VAT) in children treated for malignancy. DESIGN: We
      examined the effect of BAT activity on weight, SAT, and VAT in 32 pediatric
      patients with cancer whose positron emission tomography-computed tomography (PET
      CT) scans at diagnosis showed no BAT activity. Changes in weight, SAT, and VAT
      from diagnosis to remission for children with metabolically active BAT at disease
      free follow-up (BAT+) were compared with those in children without visualized BAT
      when free of disease (BAT-). RESULTS: Follow-up PET-CT studies (4.7 +/- 2.4 mo
      later) after successful treatment of the cancer showed BAT+ in 19 patients but no
      active BAT (BAT-) in 13 patients. BAT+ patients, in comparison with BAT-
      patients, gained significantly less weight (3.3 +/- 6.6% compared with 11.0 +/-
      11.6%; P = 0.02) and had significantly less SAT (18.2 +/- 26.5% compared with
      67.4 +/- 71.7%; P = 0.01) and VAT (22.6 +/- 33.5% compared with 131.6 +/- 171.8%;
      P = 0.01) during treatment. Multiple regression analysis indicated that the
      inverse relations between BAT activation and measures of weight, SAT, and VAT
      persisted even after age, glucocorticoid treatment, and the season when the PET
      CT scans were obtained were accounted for. CONCLUSION: The activation of BAT in
      pediatric patients undergoing treatment of malignancy is associated with
      significantly less adipose accumulation. This trial was registered at
      clinicaltrials.gov as NCT01517581.

PMID- 22456660
TI  - Eating patterns and type 2 diabetes risk in men: breakfast omission, eating
      frequency, and snacking.
AB  - BACKGROUND: Little is known about the association between eating patterns and
      type 2 diabetes (T2D) risk. OBJECTIVE: The objective of this study was to
      prospectively examine associations between breakfast omission, eating frequency,
      snacking, and T2D risk in men. DESIGN: Eating patterns were assessed in 1992 in a
      cohort of 29,206 US men in the Health Professionals Follow-Up Study who were free
      of T2D, cardiovascular disease, and cancer and were followed for 16 y. We used
      Cox proportional hazards analysis to evaluate associations with incident T2D.
      RESULTS: We documented 1944 T2D cases during follow-up. After adjustment for
      known risk factors for T2D, including BMI, men who skipped breakfast had 21%
      higher risk of T2D than did men who consumed breakfast (RR: 1.21; 95% CI: 1.07,
      1.35). Compared with men who ate 3 times/d, men who ate 1-2 times/d had a higher
      risk of T2D (RR: 1.25; 95% CI: 1.08, 1.45). These findings persisted after
      stratification by BMI or diet quality. Additional snacks beyond the 3 main meals
      (breakfast, lunch, and dinner) were associated with increased T2D risk, but these
      associations were attenuated after adjustment for BMI. CONCLUSIONS: Breakfast
      omission was associated with an increased risk of T2D in men even after
      adjustment for BMI. A direct association between snacking between meals and T2D
      risk was mediated by BMI.

PMID- 22456661
TI  - Comparison of indicators of iron deficiency in Kenyan children.
AB  - BACKGROUND: In the absence of a feasible, noninvasive gold standard, iron
      deficiency (ID) is best measured by the use of multiple indicators. However, the
      choice of an appropriate single iron biomarker to replace the multiple-criteria
      model for screening for ID at the population level continues to be debated.
      OBJECTIVE: We compared ID defined as >= 2 of 3 abnormal ferritin (< 12 MUg/L),
      soluble transferrin receptor (TfR; > 8.3 mg/L), or zinc protoporphyrin (ZP; > 80
      MUmol/mol) concentrations (ie, multiple-criteria model) with ID defined by
      abnormal concentrations of any of the independent candidate iron biomarkers
      (ferritin alone, TfR alone, or ZP alone) and TfR/ferritin index (ID, > 500).
      Values either were adjusted for inflammation [as measured by C-reactive protein
      (> 5 mg/L) and alpha(1)-acid glycoprotein (> 1 g/L) before applying cutoffs for
      ID] or were unadjusted. DESIGN: In this community-based cluster survey, capillary
      blood was obtained from 680 children (aged 6-35 mo) for measurement of iron
      status by using ferritin, TfR, and ZP. RESULTS: On the basis of the multiple
      criteria model, the mean (+/-SE) prevalence of ID was 61.9 +/- 2.2%, whereas the
      prevalences based on abnormal ferritin, TfR, or ZP concentrations or an abnormal
      TfR/ferritin index were 26.9 +/- 1.7%, 60.9 +/- 2.2%, 82.8 +/- 1.6%, and 43.1 +/-
      2.3%, respectively, for unadjusted values. The prevalences of ID were higher for
      adjusted values only for low ferritin and an elevated TfR/ferritin index compared
      with the unadjusted values. The kappa statistics for agreement between the
      multiple-criteria model and the other iron indicators ranged from 0.35 to 0.88;
      TfR had the best agreement (kappa = 0.88) with the multiple-criteria model.
      Positive predictive values of ID based on the other iron indicators in predicting
      ID based on the multiple-criteria model were highest for ferritin and TfR.
      Receiver operating characteristic curve analysis indicated that TfR (AUC = 0.94)
      was superior to the other indicators in diagnosing ID based on the multiple
      criteria model (P < 0.001). The inflammation effect did not appear to alter these
      observations appreciably. CONCLUSION: TfR better estimates the prevalence of ID
      in preschoolers than do ferritin, ZP, and the TfR/ferritin index on the basis of
      multiple indexes in a high inflammation, resource-poor setting. This trial was
      registered at clinicaltrials.gov as NCT101088958.

PMID- 22456662
TI  - Proteomic analysis shows the upregulation of erythrocyte dematin in zinc
      restricted human subjects.
AB  - BACKGROUND: Although the importance of adequate zinc intake has been known for
      decades, the estimated global prevalence of zinc deficiency remains high. This
      substantiates the need for a specific and sensitive status assessment tool.
      OBJECTIVE: The objective was to evaluate erythrocyte zinc transporters as
      candidate molecules with the potential of being a biomarker of dietary zinc
      status in humans. DESIGN: A 24-d observational study with acclimation (7 d, 10.4
      mg Zn/d), zinc-depletion (10 d, 0.3 mg Zn/d), and zinc-repletion (7 d, 29.5 mg
      Zn/d) phases was conducted in healthy men (n = 9). Proteomic approaches including
      Western blot analyses and tandem mass spectrometry were implemented to identify
      the zinc responsiveness of selected red blood cell membrane proteins. RESULTS:
      Zinc transporter 1 (ZnT1) and Zrt/Irt-like proteins ZIP8 and ZIP10 were detected
      in human erythrocyte membranes. No effects of short-term dietary zinc depletion
      were observed on the amounts of these proteins. However, changes in a
      cytoskeletal protein, dematin, by zinc depletion were identified through the
      nonspecific signals produced by an anti-ZIP8 antibody. This response was further
      validated by a dematin-specific antibody and with erythrocytes collected from
      mice fed a zinc-deficient diet. CONCLUSIONS: The presence of ZnT1, ZIP8, and
      ZIP10 in human red blood cells implicates their role in the regulation of
      cellular zinc metabolism in the human erythroid system. The zinc responsiveness
      of membrane dematin suggests its capability to serve as a biomarker for dietary
      zinc depletion and its involvement in impaired erythroid membrane fragility by
      zinc restriction. This trial was registered at clinicaltrials.gov as NCT01221129.

PMID- 22456663
TI  - Adult obesity susceptibility variants are associated with greater childhood
      weight gain and a faster tempo of growth: the 1946 British Birth Cohort Study.
AB  - BACKGROUND: Longitudinal growth associations with genetic variants identified for
      adult BMI may provide insights into the timing of obesity susceptibility.
      OBJECTIVE: The objective was to explore associations of known BMI loci with
      measures of body size from birth to adulthood. DESIGN: A total of 2537
      individuals from a longitudinal British birth cohort were genotyped for 11
      genetic variants robustly associated with adult BMI (in/near FTO, MC4R, TMEM18,
      GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, SH2B1, and MTCH2). We derived an
      obesity-risk-allele score, comprising the sum of BMI-increasing alleles in each
      individual, and examined this for an association with birth weight and repeated
      measures of weight, height, and BMI SD scores (SDS) at 11 time points between
      ages 2 and 53 y. RESULTS: The obesity-risk-allele score showed borderline
      significant association with birth weight (0.019 SDS/allele; P = 0.05) and was
      more clearly associated with higher weight and BMI at all time points between
      ages 2 and 53 y; the strongest associations with weight occurred at ages 11 and
      20 y (both 0.056 SDS/allele). In longitudinal analyses, the score was positively
      associated with weight gain only between birth and 11 y (0.003 SDS/allele per
      year; 95% CI: 0.001, 0.004; P = 0.001). The risk-allele score was associated with
      taller height at 7 y (0.031 SDS/allele; P = 0.002) and greater height gains
      between 2 and 7 y (0.007 SDS/allele per year; P < 0.001), but not with adult
      height (P = 0.5). CONCLUSIONS: The combined effect of adult obesity
      susceptibility variants on weight gain was confined to childhood. These variants
      conferred a faster tempo of height growth that was evident before the pubertal
      years.

PMID- 22456673
TI  - Radioactive fallout in the United States due to the Fukushima nuclear plant
      accident.
AB  - The release of radioactivity into the atmosphere from the damaged Fukushima
      Daiichi nuclear power plant started on March 12th, 2011. Among the various
      radionuclides released, iodine -131 ((131)I) and cesium isotopes ((137)Cs and
      (134)Cs) were transported across the Pacific Ocean and reached the United States
      on 17-18 March 2011. Consequently, an elevated level of fission products (131)I,
      (132)I, (132)Te, (134)Cs and (137)Cs were detected in air, water, and milk
      samples collected across the United States between March 17 and April 4, 2011.
      The continuous monitoring of activities over a period of 25 days and spatial
      variations across more than 100 sampling locations in the United States made it
      possible to characterize the contaminated air masses. For the entire period, the
      highest detected activity values ranged from less than 1 m Bq m(-3) to 31 m Bq m(
      3) for the particulate (131)I, and up to 96 m Bq m(-3) for the gaseous (131)I
      fraction.

PMID- 22456678
TI  - AT14A mediates the cell wall-plasma membrane-cytoskeleton continuum in
      Arabidopsis thaliana cells.
AB  - AT14A has a small domain that has sequence similarities to integrins from
      animals. Integrins serve as a transmembrane linker between the extracellular
      matrix and the cytoskeleton, which play critical roles in a variety of biological
      processes. Because the function of AT14A is unknown, Arabidopsis thaliana AT14A,
      which is a transmembrane receptor for cell adhesion molecules and a middle member
      of the cell wall-plasma membrane-cytoskeleton continuum in plants, has been
      described. AT14A, co-expressed with green fluorescent protein (GFP), was found to
      localize mainly to the plasma membrane. The mutant Arabidopsis at14a-1 cells
      exhibit various phenotypes with cell shape, cell cluster size, thickness, and
      cellulose content of cell wall, the adhesion between cells, and the adhesion of
      plasma membrane to cell wall varied by plasmolysis. Using direct staining of
      filamentous actin and indirect immunofluorescence staining of microtubules,
      cortical actin filaments and microtubules arrays were significantly altered in
      cells, either where AT14A was absent or over-expressed. It is concluded that
      AT14A may be a substantial middle member of the cell wall-plasma membrane
      cytoskeleton continuum and play an important role in the continuum by regulating
      cell wall and cortical cytoskeleton organization.

PMID- 22456679
TI  - Enhanced electronic conductivity by controlled self-doping in pyrochlores.
AB  - Most 5d transition-metal (TM) pyrochlores exhibit metallic behavior, but 3d and
      4d TM pyrochlores are generally electronic semiconductors or insulators. Here, we
      report a semiconductor-metal transition induced by introducing excess Ti metal as
      interstitials into Y(2)Ti(2)O(7). These Ti interstitials prefer anion vacant 8a
      sites or bridge sites between two neighboring cations along the <010> direction.
      Density functional theory calculations suggest that an increased electronic
      conductivity originates from the interplay between the extra Ti and its
      neighboring cations. These findings suggest a means for achieving metallic
      behavior in semiconducting pyrochlore oxides and tuning the electronic conduction
      in pyrochlores for their electrochemical applications in solid oxide fuel cells.

PMID- 22456680
TI  - Grain size effects in polycrystalline gold nanoparticles.
AB  - We report a structure-property relationship in gold nanoparticles (NPs), grain
      size effects, which not only allow material properties observed on different
      characteristic length scales to be engineered in a single NP but further enhance
      those properties due to the coupling among different-size grains. The grain size
      effects were achieved by creating polycrystalline gold NPs (pAuNPs) with two
      distinct grain-size populations (5 and 1 nm) comparable to electron mean free
      path and electron Fermi wavelength (EFW), respectively. Successful integration of
      molecular and plasmonic properties into a single nanostructure without additional
      fluorophores enables these highly polycrystalline AuNPs to serve as multimodal
      probes in a variety of optical microscopic imaging techniques.

PMID- 22456681
TI  - Segmental acne versus mosaic conditions with acne lesions.
AB  - Acne rarely presents in segmental patterns, which are encountered only in
      cutaneous mosaicism. We report herein two cases of segmentally arranged acne and
      systematically review the literature on the topic. Beside already known mosaic
      conditions which may show primary lesions typical of acne, i.e. nevus
      comedonicus, Happle-Tinschert syndrome, acne superimposed on epidermal nevi and
      mosaic Apert syndrome, we introduce the possibility that acne itself may present
      in a mosaic form. As from the extremely small casuistics retrieved, segmental
      acne is not present at birth, follows Blaschko lines, is polymorphous in nature
      and occurs on locations typical of common acne.

PMID- 22456682
TI  - Oxo-ester mediated native chemical ligation on microarrays: an efficient and
      chemoselective coupling methodology.
AB  - We report a highly efficient and selective method for the coupling of peptides
      and glycoconjugates bearing N-terminal cysteines to activated surfaces. This
      chemoselective method generates stable amide linkages without using any thiol
      additives.

PMID- 22456683
TI  - Irreversible phototautomerization of o-phthalaldehyde through electronic
      relocation.
AB  - The potential energy surface for the intramolecular excited state hydrogen
      transfer (IESHT) in ortho-phthalaldehyde (OPA), which generates an enol ketene,
      has been studied with ab initio calculations (MS-CASPT2//CASSCF). The goal of our
      study is to establish the mechanistic factors that make the primary
      phototautomerization step irreversible. Similar to what we recently described for
      ortho-nitrobenzaldehyde (NBA) (Migani et al., Chem. Commun., 2011, 47, 6383
      6385), the IESHT in OPA is characterized by the relocation of two electrons from
      the in-plane to the out-of-plane orbital system. Consistent with this, OPA has
      the same IESHT mechanism as NBA. The first step of ketene formation is the
      hydrogen transfer, which starts on an (n, pi*) state. The reaction coordinate
      goes through a conical intersection with the ground state and leads to a
      biradical intermediate with a bent ketene moiety. The second step is the
      linearization of the ketene moiety, which is associated to a change in the
      electronic configuration from biradical to ketene. Because of the electron
      relocation, the reverse transfer is similar to a Woodward-Hoffmann forbidden
      process with a sizeable barrier. This makes the tautomerization irreversible and
      allows the ketene to react further to biphthalide and benzaldehyde. Together with
      our previous NBA study, we establish the electronic relocation mechanism as a new
      mechanism for IESHT. This mechanism explains the different reactivity of OPA and
      NBA compared to organic photoprotectors, where the IESHT is reversed on a very
      short time scale.

PMID- 22456684
TI  - Injectable hydrogels for central nervous system therapy.
AB  - Diseases and injuries of the central nervous system (CNS) including those in the
      brain, spinal cord and retina are devastating because the CNS has limited
      intrinsic regenerative capacity and currently available therapies are unable to
      provide significant functional recovery. Several promising therapies have been
      identified with the goal of restoring at least some of this lost function and
      include neuroprotective agents to stop or slow cellular degeneration,
      neurotrophic factors to stimulate cellular growth, neutralizing molecules to
      overcome the inhibitory environment at the site of injury, and stem cell
      transplant strategies to replace lost tissue. The delivery of these therapies to
      the CNS is a challenge because the blood-brain barrier limits the diffusion of
      molecules into the brain by traditional oral or intravenous routes. Injectable
      hydrogels have the capacity to overcome the challenges associated with drug
      delivery to the CNS, by providing a minimally invasive, localized, void-filling
      platform for therapeutic use. Small molecule or protein drugs can be distributed
      throughout the hydrogel which then acts as a depot for their sustained release at
      the injury site. For cell delivery, the hydrogel can reduce cell aggregation and
      provide an adhesive matrix for improved cell survival and integration.
      Additionally, by choosing a biodegradable or bioresorbable hydrogel material, the
      system will eventually be eliminated from the body. This review discusses both
      natural and synthetic injectable hydrogel materials that have been used for drug
      or cell delivery to the CNS including hyaluronan, methylcellulose, chitosan,
      poly(N-isopropylacrylamide) and Matrigel.

PMID- 22456685
TI  - Magnifying loupes versus microscope for microdiscectomy and microdecompression.
AB  - STUDY DESIGN: Consecutive case series of 51 patients in each group--single
      surgeon experience. OBJECTIVE: Comparing magnifying loupes and microscopes for
      microdiscectomy and microdecompression. SUMMARY OF BACKGROUND DATA: Prospective
      peroperative data and retrospective outcome data. METHODS: All patients had
      unilateral single-level magnetic resonance imaging-proven radicular pain. All
      relevant preoperative, peroperative, and postoperative data were collected
      prospectively, including operating time, complications, and return to the
      preprolapse functional level. Retrospective patient satisfaction, employment
      level, workman's compensation claim status, smoking status, pain, and functional
      outcome scores were collected through a telephonic interview. RESULTS: The
      microscope group was significantly (P < 0.05) better than the loupes group with
      respect to patient outcome and earlier return of the preprolapse functional
      level. Patient satisfaction scores, Visual Analogue Scores for pain, and rate of
      complications were also better in the microscope group but were not statistically
      significant at P < 0.05. CONCLUSIONS: Microscopes are better than loupes as they
      provide a much better visualization, are more comfortable for the surgeon, and
      are a much better teaching tool.

PMID- 22456686
TI  - Radiographic assessment of thoracolumbar fractures based on axial zones.
AB  - STUDY DESIGN: Retrospective study of computed tomography imaging of patients with
      thoracolumbar (TL) fractures. OBJECTIVE: To propose an axial model of spinal
      fractures based on the osteoligamentous continuity of the TL spinal segments in
      the axial plane and to determine the correlation between the 3-column theory and
      the proposed axial zone model. SUMMARY OF BACKGROUND DATA: Predicting spinal
      instability of TL fractures is based on several radiologic and clinical
      parameters. Efforts to refine fracture classification schemes to better predict
      instability continue. METHODS: Computed tomography scans of 229 consecutive
      patients who presented with TL fractures between March 2005 and April 2007 were
      reviewed. TL fractures were classified according to both the Denis 3-column
      theory and the proposed axial zone model. The incidence of column and axial zone
      injuries was determined. On the basis of these results, a treatment algorithm was
      developed. RESULTS: Zone disruption in surgical fractures was distributed as
      follows: 24 (96%) involved zone A, 25 (100%) involved zone B, 17 (68%) involved
      zone C, and 15 (60%) involved zone D. All surgical fractures involved 2 or more
      zones. Zone B was involved in all surgical fractures. The likelihood of surgical
      intervention increased as the number of zones increased, especially if the injury
      was a 2-column or 3-column injury. CONCLUSIONS: The current 3-column theory of
      spinal stability does not account for the axial component of an injury.
      Application of our proposed "axial zone model" may enhance the ability to predict
      stability, depending not only on the number of columns, but also on the number of
      zones involved in the injuries. Further clinical and biomechanical studies are
      warranted to validate this model.

PMID- 22456687
TI  - Differentiation of spinal schwannomas and myxopapillary ependymomas: MR imaging
      and pathologic features.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: The objective of this
      study is to evaluate magnetic resonance imaging and pathologic features of spinal
      schwannomas (SCHs) and myxopapillary ependymomas (MPEs) with focus on
      differentiating 2 disease entities. SUMMARY OF BACKGROUND DATA: Few studies have
      reported on the differentiation of SCHs and MPEs. METHODS: Fifty-three patients
      were retrospectively reviewed with histologically confirmed spinal SCHs (41
      patients) or MPEs (12 patients) of the cauda equina and/or conus medullaris. We
      evaluated neurological deterioration after surgery in association with the
      intraoperative findings of the tumor, as well as with the preoperative magnetic
      resonance images and postoperative histologic findings. RESULTS: Patients in the
      SCH group had a greater mean age at surgery and a greater mean disease duration.
      In the SCH group, all 24 tumors that were homogeneously hyperintense on the T2
      weighted (T2W) images showed rim enhancement on the postcontrast T1-weighted
      (T1W) images. Moreover, all 14 of the SCHs with homogeneous enhancement on the
      postcontrast T1W images were isointense on the T2W images. However, in the MPE
      group, all 8 of the tumors that were homogeneously hyperintense on T2W images
      showed homogeneous enhancement on their postcontrast T1W images. CONCLUSIONS: It
      is very important to differentiate SCHs and MPEs before surgery, because there
      are reported cases of dissemination of MPEs through cerebrospinal fluid
      throughout the neuraxis; the tumor must be removed en block to prevent this.
      Although MPEs and SCHs may have similar imaging characteristics, detailed
      examination of the magnetic resonance T2W image and postcontrast T1W image
      facilitates their differentiation.

PMID- 22456688
TI  - Percutaneous lumbar and thoracic pedicle screws: a trauma experience.
AB  - DESIGN: Retrospective case study. OBJECTIVE: Percutaneous pedicle screw (PPS)
      techniques do not allow direct visualization and may lead to erroneous screw
      placement. A technique utilizing only fluoroscopy is described. Verification of
      its accuracy and morphometric validation are presented. BACKGROUND: Minimally
      invasive spine surgical techniques, particularly PPS placement, have been growing
      in popularity. The purported benefits of minimally invasive spine surgical stated
      may be even more advantageous in the trauma setting. METHODS: Jamshidi needles
      were docked in the typical starting position verified with posterior-anterior
      image. Jamshidi needle (20 mm) was advanced ensuring that the tip remained
      lateral to the medial pedicle wall. A Kirschner (K-wire) was placed through the
      needle. Once all the K-wires were placed, a lateral image was taken confirming
      the correct trajectory and that the wire passed the posterior vertebral body
      wall. Patients with PPS fixation were retrospectively studied with postoperative
      computed tomography to verify screw accuracy. Screw grade was assessed as grade I
      when completely within the pedicle, II <2 mm, III 2-4 mm, and IV >4 mm outside
      the pedicle. Morphometrically, 40 thoracic and lumbar computed tomography scans
      of patients (<40 y) without spine fractures were reviewed. The pedicle length was
      defined as the distance from the dorsal cortical margin to the posterior
      vertebral body in the pedicle's midaxis. RESULTS: A total of 172 screws were
      placed. Eighteen percent were found to have cortical breach, but only 2.9% were
      found to have >grade II breach. The morphometric study demonstrated the pedicle
      length to range from 14.4 to 22.1 mm. The shortest was in the upper thoracic and
      the longest at L1-L2. CONCLUSIONS: The morphometric study demonstrates if a K
      wire is placed 20 mm into the bone and remains lateral to the medial pedicle wall
      and the tip just engages the vertebral body, the screw trajectory is safe
      particularly in the lower thoracic and upper lumbar spine. A smaller distance may
      be utilized in the upper thoracic. Breach rates are similar to other reports
      using other techniques; none were clinically significant. The advantage of this
      technique is the use of only PA fluoroscopy for placing all the wires
      percutaneously.

PMID- 22456689
TI  - Anti-N-methyl D-aspartate receptor encephalitis in childhood.
AB  - OBJECTIVE: To discuss the differential diagnosis of encephalitis beyond that of
      infectious etiology and to inform pediatricians about the possibility of anti-N
      methyl-D-aspartate receptor (NMDAr) encephalitis in children by highlighting its
      most important clinical features. DESCRIPTION: Three patients presented with an
      initial neuropsychiatric syndrome followed by encephalopathy and movement
      disorder. The initial neuropsychiatric features which developed over days to
      weeks included a change in personality, anxiety, confusion, and speech
      regression. This was followed by a choreoathetoid or dystonic movement disorder
      affecting the orofacial region and the limbs. After the exclusion of the major
      causes of encephalitis, NMDAr antibodies were identified in serum and
      cerebrospinal fluid, and neoplasm screening did not detect any tumor. Patients
      were submitted to immunosuppression, and two of them had a full neurological
      recovery. One of them still presents a mild dystonic posture in a limb. COMMENTS:
      Clinical signs of anti-NMDAr encephalitis in children are similar to those
      previously described in adults. Tumors are not usually detected by this age. The
      diagnosis of anti-NMDAr encephalitis must be addressed only after the exclusion
      of infectious and other recognizable causes of encephalitis. Pediatricians should
      be aware of this treatable autoimmune condition.

PMID- 22456690
TI  - Do obesity and parental history of myocardial infarction improve cardiovascular
      risk prediction?
AB  - BACKGROUND: In clinical practice, individuals at increased risk of cardiovascular
      diseases (CVD) are identified on the basis of age, sex, smoking, blood pressure,
      and serum total and high-density lipoprotein cholesterol. We examined whether CVD
      risk prediction improved when obesity (body mass index >=30 kg/m(2)) and
      premature (<70 years) parental myocardial infarction (MI) were added to the
      classical risk factor model. METHODS: Risk factors were measured in 1993-97 in
      12,818 participants (53% female) aged 35-65 in the Dutch MORGEN project. Cases of
      fatal and nonfatal CVD during 10 years of follow up were identified through
      record linkage. Classical risk factor equations, obtained by Cox proportional
      hazard analysis, were extended with obesity, paternal MI, and maternal MI. We
      calculated the net reclassification index (NRI), a measure for correct
      reclassification of subjects, to check improvement in risk prediction using 5 and
      10% increments in absolute CVD risk. RESULTS: A CVD event occurred in 280 men and
      140 women. Obesity and maternal MI were positively and significantly related to
      total CVD after adjustment for classical risk factors (both hazard ratios ~1.5).
      Adding obesity and parental MI to CVD risk prediction yielded a significant NRI
      of 4.5% in men and a non-significant NRI of 2.6% in women when 5% risk categories
      were used. For 10% categories, the NRIs were slightly larger (5.5% and 3.3%,
      respectively). The improvements in risk prediction were mainly due to obesity.
      CONCLUSION: Modest improvements in CVD risk prediction can be obtained when
      obesity and, to a lesser extent, parental MI are added to the risk function.

PMID- 22456691
TI  - Modest weight loss in moderately overweight postmenopausal women improves heart
      rate variability.
AB  - PURPOSE: To evaluate the effects of weight loss on heart rate (HR) and heart rate
      variability (HRV) parameters in overweight postmenopausal women. DESIGN AND
      METHODS: Forty-nine overweight postmenopausal women with an average body mass
      index of 28.8 +/- 1.9 kg/m(2) underwent a 12-week dietary weight-loss programme.
      Accepted variables for characterization of HRV were analysed before and after the
      weight loss by 24-h ambulatory ECG monitoring; mean and standard deviation for
      the time between normal-to-normal complexes (MeanNN and SDNN, respectively), and
      the mean of standard deviations of normal-to-normal intervals for each 5-min
      period (SDNNindex). Baseline body fat mass (FM%) and changes in body composition
      was determined by dual X-ray absorptiometry. Before and after the weight-loss
      period, total abdominal fat, intra-abdominal fat (IAAT), and subcutaneous
      abdominal fat (SCAT) were measured by single-slice MRI at L3. RESULTS: The weight
      loss of 3.9 +/- 2.0 kg was accompanied by an improvement of HRV. SDNN increased
      by 9.2% (p = 0.003) and SDNNindex increased by 11.4% (p = 0.0003). MeanNN
      increased by 2.4%, reflecting a decrease in mean heart rate from 74.1 to 72.3
      beats/min (p = 0.033). Systolic blood pressure (SBP) decreased by 2.7%, total
      cholesterol by 5.1% and high-sensitivity C-reactive protein (hsCRP) by 15.8% (p =
      0.002). Improvements in SDNN and cholesterol were correlated with weight loss (r
      = -0.329, p = 0.024 and r = 0.327, p = 0.020, respectively) but changes in HR,
      SBP, and hsCRP were not. IAAT and the IAAT/SCAT-ratio were found to be negatively
      associated with HRV parameters but changes in body composition were not
      associated with changes in HRV. CONCLUSIONS: The observed improvement of HRV
      seems to be facilitated by weight loss. IAAT and the IAAT/SCAT ratio were found
      to be associated with low HRV.

PMID- 22456692
TI  - Age and gender differences of endothelial function in 4739 healthy adults: the
      HUNT3 Fitness Study.
AB  - AIMS: Endothelial dysfunction is an important marker for prognosis in patients
      with coronary heart disease. However, there are no reference values for
      endothelial function in a healthy population. Our aim was to determine the
      distribution of flow-mediated dilation (FMD) values by gender and age in healthy
      adults. METHODS: FMD was measured by ultrasound during reactive hyperaemia in the
      brachial artery of 4739 adults aged 20-89 years, who were free from self-reported
      cardiovascular or pulmonary disease. Differences in FMD across age and gender
      were analysed by multiple linear regression. RESULTS: Total mean +/- SD FMD was
      4.8 +/- 4.2%, with corresponding estimates of 4.3 +/- 3.9% for men and 5.3 +/-
      4.5% for women (p < 0.001). In total, 17% had FMD <=0%, indicating endothelial
      dysfunction. FMD decreased with increasing age in both genders up to 70 years for
      men and 80 for women (p < 0.001). In women, age-related decline in FMD was
      steepest after age 45; in men, a steady decline after age 30. In men 80 years and
      older, FMD was higher than in men aged 50-79 years. CONCLUSIONS: The distribution
      of FMD in this study is representative of the respective age and gender groups of
      a healthy population and may be a useful reference for future studies. The high
      proportion of endothelial dysfunction came as a surprise. Its age and gender
      distribution suggest that FMD <=0% precedes cardiovascular disease and that it
      may be a powerful non-invasive biomarker for identifying high-risk individuals.

PMID- 22456693
TI  - Right ventricular load and function during exercise in patients with open and
      closed atrial septal defect type secundum.
AB  - PURPOSE: This study aimed at evaluating (1) right ventricular (RV) mean power
      during exercise, (2) the contribution of flow and pressure to RV mean power, and
      (3) the impact of pulmonary artery pressure on RV function during exercise.
      METHODS: Fifty patients with atrial septal defect (ASD) type secundum (20 open,
      30 closed) were enrolled. All underwent standard echocardiography, a bicycle
      stress echocardiography, and symptom-limited cardiopulmonary exercise testing. RV
      mean power was calculated as the product of RV cardiac output and mean pulmonary
      artery pressure (mPAP). RV function was assessed using RV fractional area change
      (FAC) at rest and at peak exercise. RESULTS: RV mean power was linearly related
      with oxygen uptake (VO2) in patients with open (R (2)= 0.88; p < 0.0001) and
      closed ASD (R(2)= 0.90; p < 0.0001). The increase in RV mean power was steeper in
      open than in closed ASD patients (p < 0.0001). The change in RV cardiac output
      (7.1 +/- 3.4 vs. 5.7 +/- 2.4 l/min; p = 0.132) was not statistically different,
      but the change in mPAP (21.7 +/- 9.6 vs. 12.8 +/- 4.6 mmHg; p < 0.0001) and RV
      mean power (0.97 +/- 0.56 vs. 0.53 +/- 0.22 W; p = 0.009) were higher in patients
      with an open ASD. The change in RV FAC from rest to peak exercise was related to
      peak mPAP in open (R = -0.589; p =  0.010) and closed (R = -0.450; p = 0.021) ASD
      patients. CONCLUSION: RV mean power during exercise is higher in patients with an
      open than in patients with a closed ASD. The workload of the RV in patients with
      an open ASD is higher at rest due to a left-to-right shunt, at peak exercise due
      to an additional increase in mPAP. A higher increase in afterload may affect RV
      function during exercise.

PMID- 22456694
TI  - Effect of exercise on heart-rate response to mental stress in teenagers.
AB  - PURPOSE: We sought to determine if an exercise programme of moderate aerobic
      intensity would decrease the heart-rate response to mental stress in teenagers
      with normal hearts. METHODS: Mental stress testing (50 arithmetic problems) was
      performed in student volunteers before and after a 5-week period of rigorous
      aerobic exercise training of 2.5 h for 5 days/week. RESULTS: In the baseline
      state, the mental stress test increased the heart rate by an average of 20 +/- 12
      bpm to its observed peak at 30 s of testing (p < 0.001). Exercise training had a
      significant effect on the maximum heart rate (106 +/- 19 vs. 89 +/- 13 bpm, p <
      0.001) and on the maximum increase in heart rate with mental stress (20 +/- 12
      pre vs. 9 +/- 15 bpm post training, p < 0.001). CONCLUSION: Mental stress results
      in a marked heart response consistent with a marked neurohormonal effect. This
      response is effectively blunted by a 5-week moderately intensive exercise
      programme. These results should encourage endorsement of a regular exercise
      programme as an important lifestyle modification for improving maladaptive
      responses to stress.

PMID- 22456695
TI  - Fasting glucose, HbA1c, or oral glucose tolerance testing for the detection of
      glucose abnormalities in patients with acute coronary syndromes.
AB  - BACKGROUND: Due to the negative prognostic impact, it is important to accurately
      detect undiagnosed glucose perturbations in patients with acute coronary
      syndromes (ACS). DESIGN: This study compares oral glucose tolerance test (OGTT)
      to fasting plasma glucose (FPG) and HbA1c as screening tools. METHODS: Patients
      hospitalized for ACS had an OGTT, FPG, and HbA1c measured 4-21 (median 6) days
      after admission as a screening process for an intervention study. RESULTS: Out of
      174 patients, 75 (43%) had a normal glucose tolerance, 63 (36%) impaired glucose
      tolerance (IGT), and 36 (21%) diabetes type 2 (T2DM). Of these, 20 were non
      eligible, and of the remaining 79 patients, 52 had IGT and 27 T2DM according to
      the OGTT. In patients with IGT, the median FPG was 6.0 mmol/l and the median
      HbA1c was 39 mmol/mol. The corresponding levels in patients with T2DM were 6.3
      mmol/l and 41 mmol/mol, respectively. Seventeen of the 27 patients with T2DM
      according to OGTT had not been disclosed if the screening had been based on FPG.
      HbA1c identified two patients. CONCLUSIONS: Compared to OGTT, the use of FPG or
      HbA1c alone leaves a majority of patients with IGT or T2DM undetected when
      screening for unknown glucose perturbations as a part of total risk assessment of
      patients with ACS.

PMID- 22456697
TI  - Control of beta cell function and proliferation in mice stimulated by small
      molecule glucokinase activator under various conditions.
AB  - AIMS/HYPOTHESIS: We investigated changes in the expression of genes involved in
      beta cell function and proliferation in mouse islets stimulated with glucokinase
      activator (GKA) in order to elucidate the mechanisms by which GKA stimulates beta
      cell function and proliferation. METHODS: Islets isolated from mice were used to
      investigate changes in the expression of genes related to beta cell function and
      proliferation stimulated by GKA. In addition, Irs2 knockout (Irs2 (-/-)) mice on
      a high-fat diet or a high-fat diet containing GKA were used to investigate the
      effects of GKA on beta cell proliferation in vivo. RESULTS: In wild-type mice,
      Irs2 and Pdx1 expression was increased by GKA. In Irs2 (-/-) mice, GKA
      administration increased the glucose-stimulated secretion of insulin and Pdx1
      expression, but not beta cell proliferation. It was particularly noteworthy that
      oxidative stress inhibited the upregulation of the Irs2 and Pdx1 genes induced by
      GKA. Moreover, whereas neither GKA alone nor exendin-4 alone upregulated the
      expression of Irs2 and Pdx1 in the islets of db/db mice, prior administration of
      exendin-4 to the mice caused GKA to increase the expression of these genes.
      CONCLUSIONS/INTERPRETATION: GKA-stimulated IRS2 production affected beta cell
      proliferation but not beta cell function. Oxidative stress diminished the effects
      of GKA on the changes in expression of genes involved in beta cell function and
      proliferation. A combination of GKA and an incretin-related agent might therefore
      be effective in therapy.

PMID- 22456698
TI  - alpha-Lipoic acid regulates lipid metabolism through induction of sirtuin 1
      (SIRT1) and activation of AMP-activated protein kinase.
AB  - AIMS/HYPOTHESIS: Sirtuin 1 (SIRT1) is a longevity-associated protein, which
      regulates energy metabolism and lifespan in response to nutrient deprivation. It
      has been proposed to be a therapeutic target for obesity and metabolic syndrome.
      We investigated whether alpha-lipoic acid (ALA) exerts a lipid-lowering effect
      through regulation of SIRT1 activation and production in C(2)C(12) myotubes.
      METHODS: ALA-stimulated AMP-activated protein kinase (AMPK), acetyl-CoA
      carboxylase (ACC), adipose triacylglycerol lipase (ATGL) and fatty acid synthase
      (FAS) production, as well as intracellular triacylglycerol accumulation and fatty
      acid beta-oxidation were analysed in the absence or presence of a SIRT1 inhibitor
      (nicotinamide), SIRT1 small interfering (si) RNA and an AMPK inhibitor (compound
      C) in C(2)C(12) myotubes. Mice with streptozotocin/nicotinamide-induced diabetes
      and db/db mice fed on a high-fat diet were used to study the ALA-mediated lipid
      lowering effects in vivo. RESULTS: ALA increased the NAD(+)/NADH ratio to enhance
      SIRT1 activity and production in C(2)C(12) myotubes. ALA subsequently increased
      AMPK and ACC phosphorylation, leading to increased palmitate beta-oxidation and
      decreased intracellular triacylglycerol accumulation in C(2)C(12) myotubes. In
      cells treated with nicotinamide or transfected with SIRT1 siRNA, ALA-mediated
      AMPK/ACC phosphorylation, intracellular triacylglycerol accumulation and
      palmitate beta-oxidation were reduced, suggesting that SIRT1 is an upstream
      regulator of AMPK. ALA increased ATGL and suppressed FAS protein production in
      C(2)C(12) myotubes. Oral administration of ALA in diabetic mice fed on a high-fat
      diet and db/db mice dramatically reduced the body weight and visceral fat
      content. CONCLUSIONS/INTERPRETATION: ALA activates both SIRT1 and AMPK, which
      leads to lipid-lowering effects in vitro and in vivo. These findings suggest that
      ALA may have beneficial effects in the treatment of dyslipidaemia and obesity.

PMID- 22456700
TI  - Visible light powered self-disinfecting coatings for influenza viruses.
AB  - Influenza A viruses, the pathogens responsible for the recent swine flu outbreak
      and many historical pandemics, remain a threat to the public health. We report
      herein the fabrication of self-disinfecting surfaces from photoactive building
      nanocrystals, which can inactivate influenza viruses rapidly, spontaneously and
      continuously under visible light illumination.

PMID- 22456699
TI  - Survey of usual practice: dysphagia therapy in head and neck cancer patients.
AB  - There is no standardized dysphagia therapy for head and neck cancer patients and
      scant evidence to support any particular protocol, leaving institutions and
      individual speech-language pathologists (SLPs) to determine their own protocols
      based on "typical" practices or anecdotal evidence. To gain an understanding of
      current usual practices, a national internet-based survey was developed and
      disseminated to SLPs who treat head and neck cancer (HNC) patients. From a random
      sample of 4,000 ASHA SID13 members, 1,931 fit the inclusion criteria, and 759
      complete responses were recorded for a 39.3 % response rate. Results were
      analyzed by institution type as well as by individual clinical experience. While
      some interesting trends emerged from the data, a lack of uniformity and consensus
      regarding best practices was apparent. This is undoubtedly due to a paucity of
      research adequately addressing the efficacy of any one therapy for dysphagia in
      the HNC population.

PMID- 22456701
TI  - [Commentary on the 2010 ESC guidelines on device therapy in heart failure ].
AB  - As part of the 2010 focused update of ESC guidelines on device therapy in heart
      failure, the guidelines on pacemakers in the treatment of heart failure were
      renewed. A new feature is that cardiac resynchronization therapy (CRT) is
      indicated for New York Heart Association (NYHA) class III and IV irrespective of
      the presence of left ventricular dilatation and specified for NYHA class IV
      (patient ambulatory, stable, life expectancy >6 months). Furthermore, NYHA class
      II (but not class I) has been added when there is left bundle branch block and
      QRS duration >=150 ms. CRT is also indicated for patients in NYHA class III-IV
      with permanent atrial fibrillation and heart failure [left ventricular ejection
      fraction (LVEF) <= 35%] when QRS is >= 130 ms and ventricular rate has slowed
      either spontaneously or by AV node ablation. In patients with heart failure (NYHA
      class II-IV, LVEF <= 35%) who need a pacemaker for AV block, CRT is generally
      indicated to avoid progression of heart failure caused by right ventricular
      stimulation, also in cases of intrinsic QRS <120 ms. For patients with terminal
      heart failure who are not eligible for heart transplantation, treatment with a
      left ventricular assist device can be performed as destination therapy. The new
      guidelines expand the indication for device therapy in heart failure based on the
      newest study findings, particularly for patients in NYHA class II, and specify
      the old guidelines. There are still uncertainties that must be investigated in
      randomized trials regarding patients with permanent atrial fibrillation, the
      indication for CRT in heart block, and the question of CRT with pacemaker or
      defibrillator.

PMID- 22456703
TI  - Air density 2.7 billion years ago limited to less than twice modern levels by
      fossil raindrop imprints.
AB  - According to the 'Faint Young Sun' paradox, during the late Archaean eon a Sun
      approximately 20% dimmer warmed the early Earth such that it had liquid water and
      a clement climate. Explanations for this phenomenon have invoked a denser
      atmosphere that provided warmth by nitrogen pressure broadening or enhanced
      greenhouse gas concentrations. Such solutions are allowed by geochemical studies
      and numerical investigations that place approximate concentration limits on
      Archaean atmospheric gases, including methane, carbon dioxide and oxygen. But no
      field data constraining ground-level air density and barometric pressure have
      been reported, leaving the plausibility of these various hypotheses in doubt.
      Here we show that raindrop imprints in tuffs of the Ventersdorp Supergroup, South
      Africa, constrain surface air density 2.7 billion years ago to less than twice
      modern levels. We interpret the raindrop fossils using experiments in which water
      droplets of known size fall at terminal velocity into fresh and weathered
      volcanic ash, thus defining a relationship between imprint size and raindrop
      impact momentum. Fragmentation following raindrop flattening limits raindrop size
      to a maximum value independent of air density, whereas raindrop terminal velocity
      varies as the inverse of the square root of air density. If the Archaean
      raindrops reached the modern maximum measured size, air density must have been
      less than 2.3 kg m(-3), compared to today's 1.2 kg m(-3), but because such drops
      rarely occur, air density was more probably below 1.3 kg m(-3). The upper
      estimate for air density renders the pressure broadening explanation possible,
      but it is improbable under the likely lower estimates. Our results also disallow
      the extreme CO(2) levels required for hot Archaean climates.

PMID- 22456704
TI  - The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in
      bacteria.
AB  - Protein synthesis by ribosomes takes place on a linear substrate but at non
      uniform speeds. Transient pausing of ribosomes can affect a variety of co
      translational processes, including protein targeting and folding. These pauses
      are influenced by the sequence of the messenger RNA. Thus, redundancy in the
      genetic code allows the same protein to be translated at different rates.
      However, our knowledge of both the position and the mechanism of translational
      pausing in vivo is highly limited. Here we present a genome-wide analysis of
      translational pausing in bacteria by ribosome profiling--deep sequencing of
      ribosome-protected mRNA fragments. This approach enables the high-resolution
      measurement of ribosome density profiles along most transcripts at unperturbed,
      endogenous expression levels. Unexpectedly, we found that codons decoded by rare
      transfer RNAs do not lead to slow translation under nutrient-rich conditions.
      Instead, Shine-Dalgarno-(SD)-like features within coding sequences cause
      pervasive translational pausing. Using an orthogonal ribosome possessing an
      altered anti-SD sequence, we show that pausing is due to hybridization between
      the mRNA and 16S ribosomal RNA of the translating ribosome. In protein-coding
      sequences, internal SD sequences are disfavoured, which leads to biased usage,
      avoiding codons and codon pairs that resemble canonical SD sites. Our results
      indicate that internal SD-like sequences are a major determinant of translation
      rates and a global driving force for the coding of bacterial genomes.

PMID- 22456706
TI  - Differential positioning of adherens junctions is associated with initiation of
      epithelial folding.
AB  - During tissue morphogenesis, simple epithelial sheets undergo folding to form
      complex structures. The prevailing model underlying epithelial folding involves
      cell shape changes driven by myosin-dependent apical constriction. Here we
      describe an alternative mechanism that requires differential positioning of
      adherens junctions controlled by modulation of epithelial apical-basal polarity.
      Using live embryo imaging, we show that before the initiation of dorsal
      transverse folds during Drosophila gastrulation, adherens junctions shift basally
      in the initiating cells, but maintain their original subapical positioning in the
      neighbouring cells. Junctional positioning in the dorsal epithelium depends on
      the polarity proteins Bazooka and Par-1. In particular, the basal shift that
      occurs in the initiating cells is associated with a progressive decrease in Par-1
      levels. We show that uniform reduction of the activity of Bazooka or Par-1
      results in uniform apical or lateral positioning of junctions and in each case
      dorsal fold initiation is abolished. In addition, an increase in the Bazooka/Par
      1 ratio causes formation of ectopic dorsal folds. The basal shift of junctions
      not only alters the apical shape of the initiating cells, but also forces the
      lateral membrane of the adjacent cells to bend towards the initiating cells,
      thereby facilitating tissue deformation. Our data thus establish a direct link
      between modification of epithelial polarity and initiation of epithelial folding.

PMID- 22456707
TI  - Geoscience: Fossil raindrops and ancient air.

PMID- 22456708
TI  - Local generation of glia is a major astrocyte source in postnatal cortex.
AB  - Glial cells constitute nearly 50% of the cells in the human brain. Astrocytes,
      which make up the largest glial population, are crucial to the regulation of
      synaptic connectivity during postnatal development. Because defects in astrocyte
      generation are associated with severe neurological disorders such as brain
      tumours, it is important to understand how astrocytes are produced. Astrocytes
      reportedly arise from two sources: radial glia in the ventricular zone and
      progenitors in the subventricular zone, with the contribution from each region
      shifting with time. During the first three weeks of postnatal development, the
      glial cell population, which contains predominantly astrocytes, expands 6-8-fold
      in the rodent brain. Little is known about the mechanisms underlying this
      expansion. Here we show that a major source of glia in the postnatal cortex in
      mice is the local proliferation of differentiated astrocytes. Unlike glial
      progenitors in the subventricular zone, differentiated astrocytes undergo
      symmetric division, and their progeny integrate functionally into the existing
      glial network as mature astrocytes that form endfeet with blood vessels, couple
      electrically to neighbouring astrocytes, and take up glutamate after neuronal
      activity.

PMID- 22456709
TI  - Crystal structure of a membrane-embedded H+-translocating pyrophosphatase.
AB  - H(+)-translocating pyrophosphatases (H(+)-PPases) are active proton transporters
      that establish a proton gradient across the endomembrane by means of
      pyrophosphate (PP(i)) hydrolysis. H(+)-PPases are found primarily as homodimers
      in the vacuolar membrane of plants and the plasma membrane of several protozoa
      and prokaryotes. The three-dimensional structure and detailed mechanisms
      underlying the enzymatic and proton translocation reactions of H(+)-PPases are
      unclear. Here we report the crystal structure of a Vigna radiata H(+)-PPase
      (VrH(+)-PPase) in complex with a non-hydrolysable substrate analogue,
      imidodiphosphate (IDP), at 2.35 A resolution. Each VrH(+)-PPase subunit consists
      of an integral membrane domain formed by 16 transmembrane helices. IDP is bound
      in the cytosolic region of each subunit and trapped by numerous charged residues
      and five Mg(2+) ions. A previously undescribed proton translocation pathway is
      formed by six core transmembrane helices. Proton pumping can be initialized by
      PP(i) hydrolysis, and H(+) is then transported into the vacuolar lumen through a
      pathway consisting of Arg 242, Asp 294, Lys 742 and Glu 301. We propose a working
      model of the mechanism for the coupling between proton pumping and PP(i)
      hydrolysis by H(+)-PPases.

PMID- 22456713
TI  - From dewetting to wetting molecular layers: C60 on CaCO3(10 14) as a case study.
AB  - We report the formation of extended molecular layers of C(60) molecules on a
      dielectric surface at room temperature. In sharp contrast to previous C(60)
      adsorption studies on prototypical ionic crystal surfaces, a wetting layer is
      obtained when choosing the calcite (CaCO(3))(10 14) surface as a substrate. Non
      contact atomic force microscopy data reveal an excellent match of the hexagonal
      lattice of the molecular layer with the unit cell dimension of CaCO(3)(10 14) in
      the [01 10] direction, while a lattice mismatch along the [ 4 261] direction
      results in a large-scale moire modulation. Overall, a (2 * 15) wetting layer is
      obtained. The distinct difference observed microscopically upon C(60) adsorption
      on CaCO(3)(10 14) compared to other dielectric surfaces is explained by a
      macroscopic picture based on surface energies. Our example demonstrates that this
      simple surface-energy based approach can provide a valuable estimate for choosing
      molecule-insulator systems suitable for molecular self-assembly at room
      temperature.

PMID- 22456714
TI  - Common and unusual urogenital Crohn's disease complications: spectrum of cross
      sectional imaging findings.
AB  - Involvement of the urinary tract and genital organs is not uncommon in patients
      affected with Crohn's disease (CD). Occurring in both sexes, uro-gynecological
      complications are often clinically unsuspected because of the dominant intestinal
      or systemic symptoms. Knowledge of their manifestations and cross-sectional
      imaging appearances is necessary to recognize and report them, since correct
      medical or surgical treatment choice with appropriate specialist consultation
      allows to prevent further complications. Besides uncomplicated urinary tract
      infections that usually do not require imaging, urolithiasis and pyelonephritis
      represent the most commonly encountered urinary disorders: although very useful,
      use of computed tomography (CT) should be avoided whenever possible, to limit
      lifetime radiation exposure. Hydronephrosis due to ureteral inflammatory
      entrapment and enterovesical fistulization may result from penetrating CD, and
      require precise imaging assessment with contrast-enhanced CT to ensure correct
      surgical planning. Representing the majority of genital complication, ano- and
      rectovaginal fistulas and abscesses frequently complicate perianal inflammatory
      CD and are comprehensively investigated with high-resolution perianal MRI
      acquired with phased-array coils, high-resolution T2-weighted sequences and
      intravenous contrast. Finally, rare gynecological manifestations including
      internal genital fistulas, vulvar and male genital involvement are discussed.

PMID- 22456710
TI  - A unique regulatory phase of DNA methylation in the early mammalian embryo.
AB  - DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly
      accepted that the paternal genome is actively depleted of 5-methylcytosine at
      fertilization, followed by passive loss that reaches a minimum at the blastocyst
      stage. However, this model is based on limited data, and so far no base
      resolution maps exist to support and refine it. Here we generate genome-scale DNA
      methylation maps in mouse gametes and from the zygote through post-implantation.
      We find that the oocyte already exhibits global hypomethylation, particularly at
      specific families of long interspersed element 1 and long terminal repeat
      retroelements, which are disparately methylated between gametes and have lower
      methylation values in the zygote than in sperm. Surprisingly, the oocyte
      contributes a unique set of differentially methylated regions (DMRs)--including
      many CpG island promoters--that are maintained in the early embryo but are lost
      upon specification and absent from somatic cells. In contrast, sperm-contributed
      DMRs are largely intergenic and become hypermethylated after the blastocyst
      stage. Our data provide a genome-scale, base-resolution timeline of DNA
      methylation in the pre-specified embryo, when this epigenetic modification is
      most dynamic, before returning to the canonical somatic pattern.

PMID- 22456715
TI  - Gallbladder and muscular endometriosis: a case report.
AB  - A 55-year-old woman referred to Radiology Department, with abdominal mass and
      chronic indefinite and vague abdominal pain, most severe in right hypochondrium
      and accentuated during menstruation. A history of two cesarean sections was
      revealed. The patient underwent an ultrasound and Computed Tomography with
      intravenous contrast media revealing the presence of gallbladder and abdominal
      wall hyperenhancing masses. Finally, Magnetic Resonance study with intravenous
      administration of paramagnetic contrast media confirmed the involvement of
      gallbladder by a solid tissue and the presence of a solid nodule on the abdominal
      wall. Considering imaging features and the contrast enhancement of the nodules,
      the patient was sent to surgery. Surgical removal of both gallbladder and
      abdominal solid implant was performed and histology confirmed the diagnosis of
      gallbladder and abdominal wall endometriosis.

PMID- 22456716
TI  - Auxiliary basis sets for density-fitted correlated wavefunction calculations:
      weighted core-valence and ECP basis sets for post-d elements.
AB  - We report optimised auxiliary basis sets for the resolution-of-the-identity (or
      density-fitting) approximation of two-electron integrals in second-order Moller
      Plesset perturbation theory (MP2) and similar electronic structure calculations
      with correlation-consistent basis sets for the post-d elements Ga-Kr, In-Xe, and
      Tl-Rn. The auxiliary basis sets are optimised such that the density-fitting error
      is negligible compared to the one-electron basis set error. To check to which
      extent this criterion is fulfilled we estimated for a test set of 80 molecules
      the basis set limit of the correlation energy at the MP2 level and evaluated the
      remaining density-fitting and the one-electron basis set errors. The resulting
      auxiliary basis sets are only 2-6 times larger than the corresponding one
      electron basis sets and lead in MP2 calculations to speed-ups of the integral
      evaluation by one to three orders of magnitude. The density-fitting errors in the
      correlation energy are at least hundred times smaller than the one-electron basis
      set error, i.e. in the order of only 1-100 MUH per atom.

PMID- 22456722
TI  - Injectable systems and implantable conduits for peripheral nerve repair.
AB  - Acute sensory problems following peripheral nerve injury include pain and loss of
      sensation. Approximately 360,000 people in the United States suffer from upper
      extremity paralytic syndromes every year. Restoration of sufficient functional
      recovery after long-gap peripheral nerve damage remains a clinical challenge.
      Potential nerve repair therapies have increased in the past decade as the field
      of tissue engineering expands. The following review describes the use of
      biomaterials in nerve tissue engineering. Namely, the use of both synthetic and
      natural biomaterials, including non-degradable and degradable nerve grafts, is
      addressed. The enhancement of axonal regeneration can be achieved by further
      modification of the nerve guides. These approaches include injectable hydrogel
      fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are
      a class of liquid-gel biomaterials with high water content. Injectable and
      gelling hydrogels can serve as growth factor delivery vehicles and cell carriers
      for tissue engineering applications. While natural hydrogels and polymers are
      suitable for short gap nerve repair, the use of polymers for relatively long gaps
      remains a clinical challenge.

PMID- 22456723
TI  - A novel nanosized {Co16} metallamacrocycle incorporating four linear {Co4}
      subunits bridged by polytriazolate ligands.
AB  - The solvothermal reactions of Co(II) salts and three rigid polytriazolate ligands
      lead to a linear Co(4) cluster, [Co(4)(3,5
      bptp)(2)(OMe)(2)(NO(3))(2)(MeOH)(2)].1.5H(2)O.MeCN (1), and a square-shaped
      {Co(16)} metallamacrocycle, [Co(16)(1,3-bptb)(4)(3,5
      bptpt)(4)(OMe)(12)(H(2)O)(2)].25H(2)O (2), which comprises four linear {Co(4)}
      subunits similar to those of 1 bridged by the longer 3,5-bptpt(3-) ligands into a
      nanoscale molecular square.

PMID- 22456724
TI  - High-energy 'composite' layered manganese-rich cathode materials via controlling
      Li2MnO3 phase activation for lithium-ion batteries.
AB  - The 'composite' layered materials for lithium-ion batteries have recently
      attracted great attention owing to their large discharge capacities. Here, the
      0.5Li(2)MnO(3).0.5LiMn(0.42)Ni(0.42)Co(0.16)O(2)'composite' layered manganese
      rich material is prepared and characterized by the synchrotron X-ray powder
      diffraction (SXPD). The relationship between its electrochemical performance and
      its 'composite' components, the Li(2)MnO(3) phase activation process during
      cycling and the cycle stability of this material at room temperature are
      elucidated based on its kinetic controlled electrochemical properties, dQ/dV
      curves and Raman scattering spectroscopies associated with different initial
      charge-discharge current densities (5 mA g(-1), 20 mA g(-1) and 50 mA g(-1)), cut
      off voltages (4.6 V and 4.8 V) and cycle numbers (50 cycles and 150 cycles).
      Furthermore, its reaction pathways are tracked via a firstly introduced
      integrated compositional phase diagram of four components, Li(2)MnO(3),
      LiMn(0.42)Ni(0.42)Co(0.16)O(2), MO(2) (M = Mn(1-alpha-beta)Ni(alpha)Co(beta); 0
      <=alpha<= 5/12, 0 <=beta<= 1/6) and LiMnO(2), which turns out to be a very
      important guiding tool for understanding and utilizing this 'composite' material.

PMID- 22456725
TI  - Effects of tea and coffee on cardiovascular disease risk.
AB  - Tea and coffee have been associated with risk of cardiovascular disease (CVD),
      both positively and negatively. Epidemiological data suggest that black and green
      tea may reduce the risk of both coronary heart disease and stroke by between 10
      and 20%. Experimental and clinical trial data generally indicate either neutral
      or beneficial effects on risk factors and pathways linked to the development of
      CVD. Controversy still exists regarding the effects of coffee, where there have
      been concerns regarding associations with hypercholesterolaemia, hypertension and
      myocardial infarction. However, long term moderate intake of coffee is not
      associated with detrimental effects in healthy individuals and may even protect
      against the risk of developing type 2 diabetes. The detrimental effects of coffee
      may be associated with the acute pressor effects, most likely due to caffeine at
      high daily intakes, and lipids from boiled coffee can contribute to raised serum
      cholesterol. Genetic polymorphisms in enzymes involved in uptake, metabolism and
      excretion of tea and coffee compounds are also associated with differential
      biological effects. Potential mechanisms by which tea and coffee phytochemicals
      can exert effects for CVD protection include the regulation of vascular tone
      through effects on endothelial function, improved glucose metabolism, increased
      reverse cholesterol transport and inhibition of foam cell formation, inhibition
      of oxidative stress, immunomodulation and effects on platelet function (adhesion
      and activation, aggregation and clotting). The phytochemical compounds in tea and
      coffee and their metabolites are suggested to influence protective endogenous
      pathways by modulation of gene-expression. It is not known exactly which
      compounds are responsible for the suggestive protective effects of tea and
      coffee. Although many biologically active compounds have been identified with
      known biological effects, tea and coffee contain many unidentified compounds with
      potential bioactivity.

PMID- 22456726
TI  - A refined cluster-in-molecule local correlation approach for predicting the
      relative energies of large systems.
AB  - A refined cluster-in-molecule (CIM) method for local correlation calculations of
      large molecules is presented. In the present work, two new strategies are
      introduced to further improve the CIM approach: (1) Some medium-range electron
      correlation energies, which are neglected in the previous CIM approach, are taken
      into account. (2) A much simpler procedure using only a distance threshold is
      used to construct various clusters. To cover the medium-range correlation effect
      as much as possible, some two-atom-centered clusters are built, in addition to
      one-atom-centered clusters. Our test calculations at the second order
      perturbation theory (MP2) level show that the refined CIM method can recover
      about 99.9% of the conventional MP2 correlation energy using an appropriate
      distance threshold. The accuracy of the present CIM method is capable of
      providing reliable relative energies of medium-sized systems such as polyalanines
      with 10 residues, and water molecules with 50 water molecules. For polyalanines
      with up to 30 residues, we have demonstrated that the computational cost of the
      CIM-MP2 calculation increases linearly with the molecular size, but the required
      memory and disc-space do not need to increase for large systems. The improved CIM
      method has been used to compute the relative energy of ice-like (H(2)O)(96)
      clusters (with 2400 basis functions) and to predict the dimerization energy of a
      double-helical foldamer (with 2330 basis functions). The present CIM method is
      expected to be a practical local correlation method for describing the relative
      energies of large systems.

PMID- 22456728
TI  - Polycyclic aromatic hydrocarbon-degrading bacteria from aviation fuel spill site
      at Ibeno, Nigeria.
AB  - Polycyclic aromatic hydrocarbon (PAH)-degrading bacteria were isolated from
      aviation fuel contaminated soil at Inua Eyet Ikot in Ibeno, Nigeria. PAH
      degrading bacteria in the contaminated soil were isolated by enrichment culture
      technique. Isolates with high PAH degrading potential characterized by their
      extensive growth on PAH-supplemented minimal salt medium were screened for their
      naphthalene, phenanthrene and chrysene degradability. The screening medium which
      contained selected PAHs as the sole source of carbon and energy showed that
      Micrococcus varians AFS-2, Pseudomonas putida AFS-3 and Alcaligenes faecalis AFS
      5 exhibited a concentration-dependent growth in all the PAH-compounds tested.
      There were visible changes in the color of growth medium suggesting the
      production of different metabolites. Their acclimation to different PAH
      substrates was also evident as A. faecalis AFS-5 isolated from chrysene grew well
      on other less complex aromatic compounds. The isolate exhibited best growth (0.44
      OD(600)) when exposed to 10 ppm of chrysene for 5 days and could utilize up to 90
      ppm of chrysene. This isolate and others with strong PAH-degrading potentials are
      recommended for bioremediation of PAHs in aviation fuel-contaminated sites in the
      tropics.

PMID- 22456727
TI  - Selenium:mercury molar ratios in freshwater fish from Tennessee: individual,
      species, and geographical variations have implications for management.
AB  - Vertebrates, including humans, can experience adverse effects from mercury
      consumed in fish. Humans often prefer large predatory fish that bioaccumulate
      high mercury levels. Recent attention has focused on the role of selenium
      countering mercury toxicity, but there is little research on the selenium:mercury
      molar ratios in freshwater fish. We examine selenium:mercury molar ratios in
      freshwater fish from Tennessee at Poplar Creek which receives ongoing inputs of
      mercury from the Department of Energy's Oak Ridge Y-12 facility. Our objective
      was to determine variation of the ratios within species that might affect the
      protectiveness of selenium against mercury toxicity. Within species, the ratio
      was correlated significantly and positively with fish length only for two
      species. There was great individual variation in the selenium:mercury molar ratio
      within each species, except striped bass. The lack of a clear relationship
      between the selenium:mercury molar ratio and fish length, and the intraspecific
      variation, suggests that it would be difficult to use the molar ratio in
      predicting either the risk from mercury toxicity or in devising consumption
      advisories.

PMID- 22456729
TI  - Effects of lead exposure on growth and bone biology in growing rats exposed to
      simulated high altitude.
AB  - The existence of children living at high altitude suffering from lead (Pb)
      poisoning prompted us to investigate the long term effects of this pollutant on
      growth and bone biology in growing rats maintained at simulated high altitude
      (SHA). Pb and hypoxia (HX) significantly reduced body weight (-9.4 % and -24 %; p
      < 0.01) and length (-3 % and -8 %; p < 0.01); decreased femoral ultimate load (
      16 % and -40 %; p < 0.01) and femoral energy absorption capacity (-18 % and -74
      %; p < 0.01). Oral pathologic alterations were observed in experimental groups.
      Our findings revealed growth retardation and damages on femoral and mandibular
      bones that predispose to fractures.

PMID- 22456730
TI  - Determination of vitamin A and its metabolites in rat testis: possible
      involvement of vitamin A in testicular toxicity caused by molinate.
AB  - This study was conducted to evaluate the effect of molinate on retinoids
      homeostasis in rat testis. Molinate was administrated to male Sprague-Dawley rats
      (200 mg kg(-1) in corn oil, ip). Retinoid measurements were made at 6, 12, 48 and
      168 h time points after administration. Testis levels of retinoic acid decreased
      (32 %) in a statistically significant manner at the 12 and 48 h time points.
      However, retinol and retinaldehyde were not significantly affected by molinate.
      These results suggest that molinate affects retinoic acid synthesis in testis and
      could contribute to understanding the molecular mechanism of molinate involved
      testicular toxicity.

PMID- 22456731
TI  - Your data are not a product.

PMID- 22456732
TI  - The role of ATM in response to metformin treatment and activation of AMPK.

PMID- 22456733
TI  - The role of ATM in response to metformin treatment and activation of AMPK.

PMID- 22456734
TI  - The role of ATM in response to metformin treatment and activation of AMPK.

PMID- 22456735
TI  - Gut insulin from Foxo1 loss.
AB  - Neuroendocrine cells, including those in the gut, have a vast array of functions.
      A new study shows that conditional inactivation of the gene encoding Foxo1 in
      mouse intestinal endocrine cells converts them into cells synthesizing and
      secreting insulin. Ectopic gut insulin production was sufficient to ameliorate
      glucose control in mice with conditional pancreatic beta-cell loss and diabetes
      mellitus.

PMID- 22456736
TI  - Genome-wide recombination in Chlamydia trachomatis.
AB  - A new study reports comparative genomic analysis of 52 geographically diverse
      strains of Chlamydia trachomatis. The authors reconstruct a genome-wide phylogeny
      of the species and report extensive genome-wide recombination across multiple
      lineages of this intracellular bacterial pathogen.

PMID- 22456737
TI  - Vitamin C improves the quality of somatic cell reprogramming.
AB  - The reprogramming of somatic cells to a pluripotent state is prone to errors that
      could hamper the use of this technology. A new study now shows that vitamin C
      enhances the quality of somatic cell reprogramming in mice, highlighting the
      possibility that further manipulation of culture conditions could improve this
      technology for regenerative medicine.

PMID- 22456744
TI  - Role of chemotherapy in treatments for biliary tract cancer.
AB  - The purpose of chemotherapy in patients with advanced solid cancers, including
      biliary tract cancer, is generally to improve the survival and quality of life of
      the patients. Also, adjuvant chemotherapy is expected to increase the curability
      of surgery in patients scheduled to undergo surgery. Most patients with
      unresectable biliary tract cancer develop obstructive jaundice, and biliary
      drainage is needed before any of the aforementioned treatments. Once jaundice is
      resolved by stenting of the bile duct or bilio-intestinal bypass, cholangitis
      often develops, leading to rapid deterioration of the patient's general
      condition. Therefore, the beneficial effect of chemotherapy in such patients
      remains controversial. A few randomized controlled trials have demonstrated the
      survival benefit of chemotherapy as compared with supportive care. In one of
      these trials, improvement of the quality of life was also confirmed. Recently,
      since the survival benefit of combined gemcitabine plus cisplatin therapy over
      gemcitabine alone has been demonstrated in randomized controlled clinical trials,
      this combined regimen has been recognized as a standard therapy for unresectable
      biliary tract cancer. A second-line regimen is now expected to be established for
      patients with gemcitabine-refractory biliary tract cancer, although the
      significance of second-line therapy remains unclear. One of the next issues in
      relation to chemotherapy for biliary tract cancer is the development of molecular
      targeted agents; however, few large clinical trials of such agents have been
      conducted for biliary tract cancer. Various issues in chemotherapy for biliary
      tract cancer remain to be investigated, and global cooperation is necessary to
      conduct large clinical trials.

PMID- 22456753
TI  - Relationships between phenylalanine levels, intelligence and socioeconomic status
      of patients with phenylketonuria.
AB  - OBJECTIVES: To assess intelligence and its relationship with blood phenylalanine
      concentrations and socioeconomic status in patients with phenylketonuria after 6
      to 12 years of treatment. METHODS: Sixty-three children were classified according
      to phenylalanine levels and socioeconomic status and assessed using the Wechsler
      Intelligence Scale for Children. The Statistical Package for the Social Sciences
      (SPSS) was used to analyze phenylalanine; ANOVA was used to analyze intelligence
      quotients (IQ) and phenylalanine levels; and ordinal logistic regression was used
      to analyze the likelihood of higher IQ. RESULTS: The overall IQ scores of 90.5%
      of the children were within a range from borderline intellectual deficiency to
      very high intelligence; for verbal IQ this proportion was 96.8% and 92.1% had
      performance IQ scores within this band. The categories from low to upper-medium
      socioeconomic status contained 98.4% of patients' families. The likelihood of
      having medium to high IQ was 4.29 times greater for children with good
      phenylalanine control and 4.03 greater for those from higher socioeconomic
      strata. CONCLUSIONS: Treatment prevented mental retardation in 90.5% of the
      patients. Control of phenylalanine levels and higher socioeconomic status were
      associated with higher IQ scores.

PMID- 22456754
TI  - Controlling bubbles using bubbles--microfluidic synthesis of ultra-small gold
      nanocrystals with gas-evolving reducing agents.
AB  - Microfluidic wet-chemical synthesis of nanoparticles is a growing area of
      research in chemical microfluidics, enabling the development of continuous
      manufacturing processes that overcome the drawbacks of conventional batch-based
      synthesis methods. The synthesis of ultra-small (<5 nm) metallic nanocrystals is
      an interesting area with many applications in diverse fields, but is typically
      very challenging to accomplish in a microfluidics-based system due to the use of
      a strong gas-evolving reducing agent, aqueous sodium borohydride (NaBH(4)), which
      causes uncontrolled out-gassing and bubble formation, flow disruption and
      ultimately reactor failure. Here we present a simple method, rooted in the
      concepts of multiphase mass transfer that completely overcomes this challenge-we
      simply inject a stream of inert gas bubbles into our channels that essentially
      capture the evolving gas from the reactive aqueous solution, thereby preventing
      aqueous dissolved gas concentration from reaching the solubility threshold for
      bubble nucleation. We present a simple model for coupled mass transfer and
      chemical reaction that adequately captures device behaviour. We demonstrate the
      applicability of our method by synthesizing ultra-small gold nanocrystals (<5
      nm); the quality of nanocrystals thus synthesized is further demonstrated by
      their use in an off-chip synthesis of high-quality gold nanorods. This is a
      general approach that can be extended to a variety of metallic nanomaterials.

PMID- 22456752
TI  - Social support and adaptation to the disease in men and women with psoriasis.
AB  - Social support was shown to be an important factor buffering negative effects of
      stress in a range of clinical populations. Little is known, however, about the
      role of social support in the population of patients with psoriasis although
      strong psychosocial stress has been implicated in this disease. The objective of
      this study was to evaluate the association between social support and selected
      indices of adaptation to life with the disease, including health-related quality
      of life, depressive symptoms and acceptance of life with the disease, in a sample
      of patients with psoriasis. Additionally, gender differences in these
      relationships were analyzed. One-hundred-four patients with psoriasis completed
      psychological tests measuring disease-related social support, health-related
      quality of life, depressive symptoms and acceptance of life with the disease.
      Psoriasis severity was assessed by Psoriasis Area and Severity Index. The
      patients reporting higher social support levels had significantly higher quality
      of life, lower depression levels, and higher acceptance of life with the disease.
      The strengths of these effects, however, were different in women and men. Higher
      social support was slightly more closely associated with better acceptance of
      life with the disease in men than in women. However, higher social support was
      more closely associated to lower depression and better quality of life in women
      than in men. Among different types of social support, tangible support was found
      to be the best predictor for the all adaptation indices. Effects of social
      support perceived by psoriasis patients on adaptation to the disease may be
      gender-related and exact pathways of these effects may depend on the type on the
      dimension of social support and the selected type of adaptation indicator.
      Tangible support seems the most important type of support contributing to better
      adaptation in both women and men with psoriasis.

PMID- 22456755
TI  - Lymph node yield and oncologic outcome after colorectal cancer resection.

PMID- 22456756
TI  - Therapeutic potential of gel-based injectables for vocal fold regeneration.
AB  - Vocal folds are anatomically and biomechanically unique, thus complicating the
      design and implementation of tissue engineering strategies for repair and
      regeneration. Integration of an enhanced understanding of tissue biomechanics,
      wound healing dynamics and innovative gel-based therapeutics has generated
      enthusiasm for the notion that an efficacious treatment for vocal fold scarring
      could be clinically attainable within several years. Fibroblast phenotype and
      gene expression are mediated by the three-dimensional mechanical and chemical
      microenvironment at an injury site. Thus, therapeutic approaches need to
      coordinate spatial and temporal aspects of the wound healing response in an
      injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based
      injectables for vocal fold scarring will require a keen understanding of how the
      native inflammatory response sets into motion the later extracellular matrix
      remodeling, which in turn will determine the ultimate biomechanical properties of
      the tissue. We present an overview of the challenges associated with this
      translation as well as the proposed gel-based injectable solutions.

PMID- 22456759
TI  - The role of long-range interactions in the phase behavior of ionic liquids.
AB  - The COSMO-type liquid activity coefficient models are among the most successful
      methods for the prediction of the phase behaviours of fluids containing ionic
      liquids. However, these models consider only interactions between species that
      are in close contact; in other words, the long-range Coulomb interactions, which
      are known to be important for systems containing charged species, are completely
      ignored. Here we show that the inclusion of long-range terms (with, e.g., the
      Pitzer-Debye-Huckel model) is indeed critical to obtain the correct osmotic
      coefficients and the asymptotic behaviours in the infinite dilution of IL
      solutions. However, the direct combination of PDH and COSMO-type models does not
      produce accurate activity coefficient over the whole concentration range because
      both models contain short range interactions. We show that a recent revision of
      the COSMO-SAC model, which includes the PDH contributions and a specific
      treatment of solvent-ion and ion-ion interactions, is capable of providing an
      accurate description of the properties (phase behaviour, osmotic coefficients) of
      aqueous IL solutions over the whole concentration range.

PMID- 22456757
TI  - Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with
      advance non-small cell lung cancer.
AB  - Accumulating preclinical evidence suggests that anticancer immune responses
      contribute to the success of chemotherapy. The predictive significance of tumor
      infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non
      small cell lung cancer (NSCLC) remains unknown. The aim of this study was to
      investigate the prognostic and predictive value of TIL subtypes in patients with
      advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients
      with stage III and IV NSCLC were retrospectively enrolled. The prevalence of
      CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in
      tumor tissue obtained before chemotherapy. The density of TILs subgroups was
      treated as dichotomous variables using the median values as cutoff. Survival
      curves were estimated by the Kaplan-Meier method, and differences in overall
      survival between groups were determined using the Log-rank test. Prognostic
      effects of TIL subsets density were evaluated by Cox regression analysis. The
      presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any
      clinicopathological features. Neither the prevalence of TILs nor combined
      analysis displayed obvious prognostic performances for overall survival in Cox
      regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an
      independent factor for poor response to platinum-based chemotherapy in overall
      cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell
      infiltrate within tumor environment is predictive of response to platinum-based
      neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the
      clinical relevance of the microenvironmental immunological milieu might provide
      an important clue for the design of novel strategies in cancer immunotherapy.

PMID- 22456764
TI  - An unusual case of IgA-mediated anti-glomerular basement membrane disease.
AB  - Anti-glomerular basement membrane (GBM) disease is mediated by circulating
      autoantibodies, principally IgG, targeted at the type IV collagen of GBM. The IgA
      variant of anti-GBM disease has rarely been described. We report a 65-year-old
      man with uremia, undergoing hemodialysis, who was referred because of hemoptysis.
      A chest X-ray showed diffuse infiltration in the right lung field. Laboratory
      data were remarkable for renal failure, anemia, and thrombocytopenia.
      Furthermore, laboratory evidence of microangiopathic hemolytic anemia was
      present. A kidney biopsy revealed diffuse crescentic glomerulonephritis.
      Circulating IgA anti-GBM antibody was found, as well as the presence of
      significant IgA deposition in a linear pattern along the GBM, suggesting an anti
      GBM antibody-mediated disease. The patient was treated with plasmapheresis and
      pulse steroid therapy, which resulted in an immediate improvement in the
      pulmonary hemorrhage and hematological abnormalities. However, the patient did
      not regain renal function and remained on hemodialysis. 

PMID- 22456765
TI  - Renal cell carcinoma stage migration in a single European centre over 25 years:
      effects on 5- and 10-year metastasis-free survival.
AB  - PURPOSE: To assess renal cell carcinoma (RCC) stage migration in a large European
      academic centre series over 25 years and its possible impact on patients'
      metastasis-free survival. METHODS: The pathology reports of 2,333 consecutive
      patients with RCC who underwent nephrectomy from 1984 to 2006 at our institution
      were systematically re-evaluated. Patients were pooled into four groups according
      to the date of surgery: group 1: 1984-1989, group 2: 1990-1995, group 3: 1996
      2001 and group 4: 2002-2006, respectively. Changes in pT-categories over time and
      the impact on 5- and 10-year metastasis-free survival were evaluated. RESULTS:
      Organ-confined (pT1 and pT2) tumours were found in 191/502 (38.0 %) and 372/535
      (69.5 %) surgical specimens in groups 1 and 4, respectively (p < 0.001). This
      stage migration was mainly the result of an increase in pT1a tumours (overall:
      32.6 %) from 12.5 % in group 1 to 45.8 % in group 4 and a decrease in pT3a
      tumours (overall: 24.1 %) from 46.6 % in group 1 to 11.0 % in group 4 (p <
      0.001). The mean tumour size decreased from 6.7 cm in group 1 to 4.8 cm in group
      4 (p < 0.001). In 2,152 patients with non-metastatic RCC, median follow-up was
      76.2 (interquartile range: 36.2-133.9) months. Five- and 10-year metastasis-free
      survival probabilities were 78.7 and 71.9 % in group 1, 85.3 and 80.0 % in group
      2, and 86.9 and 82.7 % in group 3, respectively. Five-year metastasis-free
      survival in group 4 was 90.3 % (p < 0.001). CONCLUSION: A statistically
      significant stage migration towards organ-confined RCC was observed in the cohort
      studied. This stage migration was accompanied by a significant improvement in
      metastasis-free survival comparing the period 1984-1989 and following time
      periods.

PMID- 22456768
TI  - Prevalence and outcome of cirrhosis patients admitted to UK intensive care: a
      comparison against dialysis-dependent chronic renal failure patients.
AB  - PURPOSE: Patients with decompensated liver cirrhosis who are admitted to
      intensive care units (ICU) are perceived, within the UK, as having a particularly
      poor prognosis. METHODS: We performed a descriptive analysis of cirrhosis
      patients admitted to general critical care units 1995-2008 compared to patients
      admitted with pre-existing chronic renal failure. Data were obtained from the
      Intensive Care National Audit and Research Centre Case Mix Programme Database
      incorporating 192 adult critical care units in England, Wales and Northern
      Ireland. RESULTS: Cirrhosis accounted for 2.6 % (16,096 patients) of total
      admissions with mean age 52.5 years and male preponderance (~60 %). Hospital
      mortality was high (>55 %) although this improved 5 % in recent years, and median
      length of stay was short (2.5 days). Mortality in cirrhotics with severe sepsis
      requiring organ support was 65-90 %, compared to 33-39 % in those without.
      Conversely, patients with chronic renal failure had lower mortality (42 %)
      despite similar characteristics and higher acute physiology and chronic health
      evaluation (APACHE) II scores. The APACHE II score under-predicted mortality in
      cirrhotics. CONCLUSIONS: Cirrhosis patients exhibit worse outcomes compared to
      pre-existing renal failure patients, despite similar characteristics. Survival
      worsens considerably with organ failure, especially with sepsis. They represent a
      small number of admissions, albeit increasing over recent years, and, in general,
      have a short ICU stay. Patients with single organ failure have acceptable
      survival rates and mortality has improved; although we have no data on those
      refused ICU admission potentially causing survival bias. Given the extremely high
      mortality in patients with multi-organ failure, support should be
      limited/withdrawn in such patients.

PMID- 22456769
TI  - NT-proBNP levels at spontaneous breathing trial help in the prediction of post
      extubation respiratory distress.
AB  - PURPOSE: To evaluate and compare the performance of NT-proBNP levels, plasma
      protein concentration, hematocrit, and fluid balance for the preceding 24 h in
      predicting the outcome of the two steps of weaning: (1) spontaneous breathing
      trial (SBT), (2) extubation. METHODS: This was a prospective observational study
      of 143 patients who were mechanically ventilated for more than 48 h (55% COPD)
      and were ready to wean. They underwent an SBT and were extubated when they passed
      the trial. Immediately before the SBT, we measured the evaluated diagnosis tools.
      RESULTS: Of 143 patients, 80 (56%) passed the SBT and were extubated. Of these,
      two were reintubated for laryngeal dyspnea, 57 had no respiratory problem during
      the next 48 h, and 21 developed post-extubation respiratory distress (26%).
      Rescue noninvasive ventilation (NIV) prevented reintubation in 15 (71%). None of
      the tested diagnosis tools predicted the outcome of the SBT. Patients who
      developed post-extubation respiratory distress were older, had lower values of
      plasma protein concentration and higher values of NT-proBNP than those who did
      not. Only NT-proBNP was an independent predictor of the occurrence of post
      extubation respiratory distress (OR 1.2; 95% CI 1.09-1.4; p = 0.003); the area
      under the ROC curve for NT-proBNP to predict post-extubation respiratory distress
      was 0.78 (95% CI 0.67-0.89; p = 0.0001). NT-proBNP was more accurate to rule out
      (negative likelihood ratio 0.09 for a cutoff of no greater than 1,000 pg/ml) than
      to rule in the risk of post-extubation respiratory distress (positive likelihood
      ratio 3.45 for a cutoff of at least 2,000 pg/ml). CONCLUSION: NT-proBNP levels at
      SBT help in the prediction of post-extubation respiratory distress and could
      identify the subgroup of extubated patients requiring close observation and/or
      prophylactic NIV.

PMID- 22456770
TI  - Remifentanil/midazolam versus fentanyl/midazolam for analgesia and sedation of
      mechanically ventilated neonates and young infants: a randomized controlled
      trial.
AB  - PURPOSE: Common opioids for analgesia and sedation of mechanically ventilated
      infants may tend to accumulate and cause prolonged sedation with an unpredictable
      extubation time. Remifentanil is a promising option due to its unique
      pharmacokinetic properties, which seem to be valid in adults as well as in
      infants. METHODS: In this double-blind, randomized, controlled trial mechanically
      ventilated neonates and young infants (<60 days) received either a remifentanil
      or fentanyl-based analgesia and sedation regimen with low dose midazolam. The
      primary endpoint of the trial was the extubation time following discontinuation
      of the opioid infusion. Secondary endpoints included efficacy and safety aspects.
      RESULTS: Between November 2006 and March 2010, we screened 431 mechanically
      ventilated infants for eligibility. The intention to treat group included 23
      infants who were assigned to receive either remifentanil (n = 11) or fentanyl (n
      = 12). Although this was designed as a pilot study, median extubation time was
      significantly shorter in the remifentanil group (80.0 min, IQR = 15.0-165.0)
      compared to the fentanyl group (782.5 min, IQR = 250.8-1,875.0) (p = 0.005).
      Remifentanil and fentanyl provided comparable efficacy with more than two-thirds
      of the measurements indicating optimal analgesia and sedation (66.4 and 70.2 %,
      respectively; p = 0.743). Overall, both groups had good hemodynamic stability and
      a comparably low incidence of adverse events. CONCLUSIONS: As neonates and young
      infants have a decreased metabolism of common opioids like fentanyl and are more
      prone to respiratory depression, remifentanil could be the ideal opioid for
      analgesia and sedation of mechanically ventilated infants.

PMID- 22456771
TI  - Quantification of recirculation as an adjuvant to transthoracic echocardiography
      for optimization of dual-lumen extracorporeal life support.
AB  - PURPOSE: Proper cannula positioning in single site veno-venous extracorporeal
      life support (vv-ELS) is cumbersome and necessitates image guidance to obtain a
      safe and stable position within the heart and the caval veins. Importantly, image
      guided cannula positioning alone is not sufficient, as possible recirculation
      cannot be quantified. METHODS AND RESULTS: We present an ultrasound dilution
      technique allowing quantification of recirculation for optimizing vv-ELS.
      CONCLUSION: We suggest quantification of recirculation in addition to image
      guidance to provide optimal vv-ELS.

PMID- 22456772
TI  - Issues associated with the use of modified texture foods.
AB  - Use of modified texture foods (MTF) is common in the geriatric population. There
      is a potential for increased prevalence of use of MTF due in part to longer
      survival of persons with dementia, those who have suffered from a stroke, as well
      as other degenerative diseases that affect chewing and swallowing. Unfortunately,
      little clinical, nutritional and sensory research has been conducted on MTF to
      inform practice. This review highlights issues identified in the literature to
      date that influence nutritional and sensory quality and acceptability of these
      foods. Use of MTF is highly associated with undernutrition, however causality is
      difficult to demonstrate due to confounding factors such as the requirement for
      feeding assistance. Knowledge gaps and considerations that need to be taken into
      account when conducting research are identified.

PMID- 22456773
TI  - Changes in blood oxidative and antioxidant parameters in a group of Chinese
      patients with age-related macular degeneration.
AB  - OBJECTIVE: To measure the oxidative and antioxidant biochemical parameters in the
      serum of Chinese patients with age-related macular degeneration (AMD) and in a
      similar age control group from the same area. DESIGN: A case-control study.
      PARTICIPANTS: 56 AMD patients ( 21 early dry, 13 geographic atrophy and 22 wet
      form) and 34 normal subjects, similar for age and sex were studied. MEASUREMENTS:
      Both groups completed a questionnaire about demographic characters and dieatry
      habit, and the levels of serum lipid peroxidation (malondialdehyde, MDA) and
      antioxidants parameters (vitamin C and E, the activities of superoxide dismutase-
      SOD, total antioxidant capacity--TAC ) were determined. RESULTS: There was a
      significantly higher frequency of daily intake of fruit and legumes in controls
      than in AMD patients. There was a significantly increased serum MDA levels and
      SOD activities, and significantly decreased serum vitamin C and total antioxidant
      capacity in AMD patients as compared to controls. The intensity of lipid
      peroxidation was higher with the progression of AMD. There was not difference in
      serum vitamin E levels between AMD patients and controls. CONCLUSION: Oxido
      reduction disturbance may be involved in the pathogenesis of AMD. There is a
      significantly decreased antioxidant capacity in AMD patients.

PMID- 22456775
TI  - Automatic video monitoring system for assessment of Alzheimer's disease symptoms.
AB  - In order to fully capture the complexity of the behavioural, functioning and
      cognitive disturbances in Alzheimer Disease (AD) and related disorders
      information and communication techniques (ICT), could be of interest. This
      article presents using 3 clinical cases the feasibility results of an automatic
      video monitoring system aiming to assess subjects involved in a clinical
      scenario. METHOD AND POPULATION: The study was conducted in an observation room
      equipped with everyday objects for use in activities of daily living. The overall
      aim of the clinical scenario was to enable the participants to undertake a set of
      daily tasks that could realistically be achieved in the setting of the
      observation room. The scenario was divided in three steps covering basic to more
      complex activities: (1) Directed activities, (2) Semi-directed activities, (3)
      Undirected ("free") activities. The assessment of each participant of the study
      was done with an automatic video monitoring system composed of a vision component
      and an event recognition component. The feasibility study involved three
      participants: two AD patients and one elderly control participant. RESULTS: The
      first result of the study was to demonstrate the feasibility of this new
      assessment method from both the patient and the technical points of view. During
      the first step the control participant performed all these activities faster than
      the two AD participants. During the second step of the scenario AD participants
      were not able to follow the correct order of the tasks and even omitted some of
      them. Finally during the last step of the scenario devoted to free activities the
      control participant chose one of the proposed activities (reading) and undertook
      this activity for almost the entire duration. In contrast, the two AD
      participants had more difficulties choosing one of the suggested activities and
      were not able to undertake any one activity in a sustained manner. DISCUSSION:
      The automatic video monitoring system presented here analyzes human behaviours
      and looks for changes in activity through the detection of the presence of people
      and their movements in real time. Once the technique has been standardized, it
      could significantly enhance the assessment of AD patients in both clinical and
      clinical trial settings as well as providing further information regarding
      patient frailty that could enhance their safety and ease caregiver burden.

PMID- 22456774
TI  - Vitamin status in elderly people in relation to the use of nutritional
      supplements.
AB  - OBJECTIVE: This study aimed to evaluate the status of several vitamins and to
      investigate the effect of regular individual supplementation on their status in
      this population. DESIGN: An observational study. SETTING: State of Burgenland,
      Austria. PARTICIPANTS: A total of 102 non-institutionalized subjects (49%
      supplementing regularly, 51% without supplementation) aged between 70-90 years
      were recruited. MEASUREMENTS: Plasma levels of vitamins A, D, E, K and C were
      determined by HPLC. The functional parameters of vitamins B1, B2 and B6, i.e. the
      activities of the erythrocyte enzymes transketolase, glutathione reductase and
      glutamic oxaloacetic transaminase, were analyzed photometrically; plasma folate
      and vitamin B12 were determined by RIA. RESULTS: The status of vitamins A, E and
      C was generally satisfactory. Eighty-eight percent and 42% of participants were
      deficient in vitamins D and K, respectively, as were 29% for B6; up to 10% of
      participants were deficient in vitamins B1, B2, B12 and folate. A considerable
      percentage of participants was, however, at risk for vitamin deficiencies
      (vitamins B1, B6, B12, folate: 20-30%, vitamin B2: 60%). Except for vitamins A
      and K, regular intake of supplements had a significant positive influence on
      vitamin levels. CONCLUSION: These results indicate that use of supplements
      significantly improved the status of several vitamins in elderly people. Due to
      age-related problems concerning the intake and digestion of nutrients, a
      moderate, regular supplementation might be a useful option for older people who
      are otherwise unable to satisfy their micronutrient requirements.

PMID- 22456776
TI  - Iron deficiency can cause cognitive impairment in geriatric patients.
AB  - OBJECTIVES: Deficiency of iron, which plays an important role in oxygen transport
      and storage, may lead to cerebral hypoxia and cognitive decline. This
      relationship which was studied in children and adults was not evaluated in the
      elderly. The objective of this study is to examine the effect of iron deficiency
      on cognitive function in the elderly. DESIGN, SETTING, PARTICIPANTS: This is a
      cross-sectional study conducted in a geriatric medicine outpatient clinic of a
      university hospital. Consecutive 2009 patients admitted to Geriatric Medicine
      outpatient clinic were examined and 622 patients who fulfilled the inclusion
      criteria were enrolled in the study. MEASUREMENTS: Comprehensive geriatric
      assessment, cognitive assessment and laboratory analysis including blood count,
      iron, total iron binding capacity, ferritin, and transferrin saturation were
      performed. RESULTS: Mean age of the study group was 72.5+/-6.5 and 439 (70.6%)
      were women. MMSE scores were moderately and significantly correlated with iron
      levels (r=0.33, p<0.001) and transferrin saturation (r=0.32, p<0.001).
      Transferrin saturation was significantly lower in the patients with dementia
      (p=0.040). It was found that patients with iron deficiency had lower MMSE scores
      (p<0.001) and this relationship was also present in patients without anemia
      (p=0.004). CONCLUSION: The results of this study revealed a negative influence of
      iron deficiency on cognitive function and this influence was independent from the
      presence of anemia. As iron deficiency can be easily diagnosed and treated,
      detecting its effect on cognitive function is of importance. Screening for iron
      deficiency and initiating appropriate treatment should be a routine part of
      comprehensive geriatric assessment.

PMID- 22456777
TI  - Telomere length, comorbidity, functional, nutritional and cognitive status as
      predictors of 5 years post hospital discharge survival in the oldest old.
AB  - BACKGROUND: Telomere length has been considered in many cross-sectional studies
      as a biomarker of aging. However the association between shorter telomeres with
      lower survival at advanced ages remains a controversial issue. This association
      could reflect the impact of other health conditions than a direct biological
      effect. OBJECTIVE: To test whether leukocyte telomere length is associated with 5
      year survival beyond the impact of other risk factors of mortality like
      comorbidity, functional, nutritional and cognitive status. DESIGN: Prospective
      study. SETTING AND PARTICIPANTS: A population representative sample of 444
      patients (mean age 85 years; 74% female) discharged from the acute geriatric
      hospital of Geneva University Hospitals (January-December 2004), since then 263
      (59.2%) had died (December 2009). MEASUREMENTS: Telomere length in leukocytes by
      flow cytometry. RESULTS: In univariate model, telomere length at baseline and
      cognitive status were not significantly associated with mortality even when
      adjusting for age (R2=9.5%) and gender (R2=1.9%). The best prognostic predictor
      was the geriatric index of comorbidity (GIC) (R2=8.8%; HR=3.85) followed by more
      dependence in instrumental (R2=5.9%; HR=3.85) and based (R2=2.3%; HR=0.84)
      activities of daily living and lower albumin levels (R2=1.5%; HR=0.97). Obesity
      (BMI>30: R2=1.6%; HR=0.55) was significantly associated with a two-fold decrease
      in the risk of mortality compared to BMI between 20-25. When all independent
      variables were entered in a full multiple Cox regression model (R2=21.4%), the
      GIC was the strongest risk predictor followed by the nutritional and functional
      variables. CONCLUSION: Neither telomeres length nor the presence of dementia are
      predictors of survival whereas the weight of multiple comorbidity conditions,
      nutritional and functional impairment are significantly associated with 5-year
      mortality in the oldest old.

PMID- 22456779
TI  - Exercise training and the control of skin blood flow in older adults.
AB  - The ability to control skin blood flow decreases with primary aging, making older
      adults less able to adequately thermoregulate and repair cutaneous wounds.
      Lifestyle factors such as physical activity, diet, and smoking might interact
      with the aging process to modulate "normal" age-associated changes in the
      cutaneous microcirculation. The main focus of this brief review is the effects of
      exercise training on the control of skin blood flow in older adults.

PMID- 22456778
TI  - Nutritional and psycho-functional status in elderly patients with Alzheimer's
      disease.
AB  - OBJECTIVES: Analysis of variations of nutritional status in relation to psycho
      functional conditions in elderly patients with mild to moderate Alzheimer's
      disease (AD) by means of bioelectrical impedance vector analysis (BIVA). DESIGN:
      Cross-sectional study. SETTING: Alzheimer Center, SS. Trinita Hospital, Cagliari
      (Italy). PARTICIPANTS: 83 free-living patients (29 men, 54 women) with mild
      moderate Alzheimer's disease, aged 66 to 96 years, and 91 age-matched controls
      (37 men and 54 women). MEASUREMENTS: Nutritional status was evaluated by
      anthropometry (weight, height, waist and upper arm circumferences, triceps
      skinfold; body mass index, BMI; arm muscle area, AMA); Mini Nutritional
      Assessment, MNA(r); bioelectrical impedance vector analysis, BIVA. Psycho
      functional status was assessed by the Mini Mental State Examination (MMSE),
      Geriatric Depression Scale (GDS), Activities of Daily Living (ADL), and
      Instrumental Activities of Daily Living (IADL). RESULTS: Compared to the control
      groups, patients with Alzheimer's disease had a worse psycho-functional and
      nutritional status. BIVA detected lower body cell mass in Alzheimer's patients
      with respect to controls (men: T2= 23.4; women: T2=27.3; p<0.01), as well as in
      the female patients with lower levels of IADL and MMSE (respectively, T2= 8.0;
      T2=7.4; p<0.05). In patients with AD, a worse psycho-functional status was
      associated with obesity. CONCLUSION: The psycho-functional decline of patients
      with AD is related to body composition variations, with a relative increase of
      fat mass with respect to the muscle component. The BIVA technique distinguished
      patients from controls and patients with different levels of cognitive decline.
      Therefore, it is a suitable tool for the screening and monitoring of nutritional
      status in Alzheimer's disease.

PMID- 22456781
TI  - Malic enzyme gene polymorphism is associated with responsiveness in circulating
      parathyroid hormone after long-term calcium supplementation.
AB  - OBJECTIVE: To identify genetic variations associated with parathyroid hormone
      (PTH) suppression after long-term calcium supplementation. DESIGN AND
      PARTICIPANTS: For high throughput SNP screening, subjects consisted of 171
      postmenopausal women without osteoporosis at the lumbar spine. A separate group
      of 19 premenpausal women were recruited for calcium absorption study.
      Postmenopausal women in the screening group were given 500 mg/day calcium
      supplementation. SETTING: Bangkok, Thailand. MEASUREMENTS: Parathyroid hormone
      (PTH) and bone mineral density (BMD) were measured at baseline and 2 years after
      calcium supplementation. High throughput single-nucleotide polymorphism (SNP)
      screening was performed by comparing estimated allele frequencies derived from
      hybridization signal intensities of pooled DNA samples on Affymetrix's 10K SNP
      genotyping microarrays based responsiveness in PTH after calcium supplementation.
      Genotyping of SNP rs1112482 in malic enzyme gene (ME1) gene, a SNP among those
      with highest odds ratio of being related to PTH suppression after calcium, was
      performed in all postmenopausal subjects in the screening group and premenopausal
      women in the calcium absorption study group in which fractional calcium
      absorption was assessed by stable isotope dilution. Data were expressed as mean
      +/- SEM. RESULTS: PTH significantly decreased after 2 years of calcium
      supplementation (4.7 +/- 1.9 vs. 4.4 +/- 1.6 pmol/L, P < 0.01). There was a
      significant increase in lumbar spine BMD (1.03 +/- 0.01 vs. 1.01 +/- 0.01 g/cm2,
      P < 0.001) but not femoral neck BMD. In 108 subjects whose PTH levels decreased
      after calcium, the suppression of PTH was higher in those with at least one C
      allele in rs1112482 of ME1 gene (-26.3 +/- 2.1 vs. -16.9 +/- 1.4%, P < 0.001).
      Fractional calcium absorption also tends to the higher in subjects in the calcium
      absorption study group with at least one C allele (n = 6) compared to those
      without the C allele (n = 13) (58.0 +/- 4.9 vs. 49.3 +/- 2.8%, P = 0.054).
      CONCLUSION: Cytosolic malic enzyme 1 gene polymorphism is associated with the
      degree of suppression of parathyroid hormone after long-term calcium
      supplementation. The effect is probably mediated through an increase in
      intestinal calcium absorption.

PMID- 22456780
TI  - New chitin complexes and their anti-aging activity from inside out.
AB  - BACKGROUND: Nutritional and topical antioxidants and immuno-modulant compounds
      play a key role in maintaining healthy skin. However, little is known about the
      combined effects antioxidant cosmeceuticals and nutricosmetics can have on the
      appearance of aging skin. OBJECTIVE: The clinical trial was designed to study the
      combined effects on skin hydration, superficial lipids, elasticity, peroxidation
      and global clinical appearance, of melatonin, Vit. E and Betaglucan (MEB)
      complexed with chitin nano-crystals administered both topically and orally.
      Clinical examinations were conducted by dermatologists. DESIGN: By a randomized
      placebo-controlled, 12 week multicenter study on 70 healthy subjects, affected
      with skin photo-aging, the anti-aging efficacy and tolerability of the combined
      activity of topical emulsion and oral hard capsules, containing MEB complexed
      with chitin nano-crystals (CN) was evaluated clinically and by biophysical non
      invasive measurements at week 4,8 and 12. RESULTS: The effects of MEB intake
      resulted significantly higher (p<0.005) than placebo for all the parameters
      evaluated by biophysical and clinical measurements. The values resulted higher
      when the active ingredients MEB were complexed with CN, whether used topically,
      orally or a combination of both (p<0.05). The positive results, observed since
      week 4, were accompanied by no side-effects throughout the entire study.
      CONCLUSION: The combined topical and oral use of MEB was associated with reduced
      wrinkling, better skin appearance and general overall wellness. When MEB were
      complexed with CN, the obtained results were statistically more positive (p<0.05)
      for all the biophysical and clinical parameters considered.

PMID- 22456782
TI  - Effects of tea drinking on auditory functions in aged subjects.
AB  - The purpose of this study was to investigate the effects of Oolong tea drinking
      on the auditory functions in aged subjects. Retrospective cohort study was
      conducted on 265 subjects who were older than 55 years old. Tea drinking was
      determined from responses to a medical and food consumption questionnaires. The
      effects of Oolong tea drinking on pure tone thresholds (PTAs) for peripheral
      hearing and pitch pattern sequence (PPS) scores for central hearing were
      analyzed. Results showed that, before adjusting for other factors, PTAs were not
      significantly different between "non-tea drinkers" and "Oolong tea drinkes". But,
      the mean PPS score was higher in the "Oolong tea drinkers" (74.5 +/- 12.7%) than
      in the "non-tea drinkers" (68.4 +/- 13.9%). After adjusting for age, gender,
      waist circumference, and other variables, Oolong tea drinking (coefficient (beta)
      +/- standard error (SE) = 2.60 +/- 0.67, P<0.001) was positively associated with
      PPS score, but not with PTAs, by multivariate linear regression analysis. In
      subgroup analysis for PPS score by gender, Oolong tea drinking showed a
      significant positive association with PPS score in males (beta+/- SE=4.75 +/-
      0.95, P<0.001), but showed association of borderline significance with PPS score
      in females (beta+/- SE=1.57 +/- 0.94, P=0.097), with adjustment of other risk
      factors. In conclusion, Oolong tea drinking was associated with better central
      auditory function, but not with peripheral hearing thresholds, especially in male
      aged subjects.

PMID- 22456783
TI  - Prevalence and factors associated with feeding difficulty in institutionalized
      elderly with dementia in Taiwan.
AB  - OBJECTIVES: The purpose of this study was to establish the prevalence rate of
      feeding difficulty and to understand the factors associated with it among people
      with dementia. DESIGN: A cross-sectional design was used. SETTING: Five nursing
      homes in Taiwan. PARTICIPANTS: Ninety-three residents with dementia were
      enrolled. MEASUREMENTS: Feeding difficulty was measured by The Edinburgh Feeding
      Evaluation in Dementia (EdFED) scale. Data included demographics, nutritional
      data, cognition, and independence were also collected. RESULTS: Residents with
      EdFED scores above five had significantly longer duration of dementia (56.3+/
      27.4 vs 42.2+/-22.8, P<0.05), greater dependence (26.2+/-20.8 vs 57.4+/-25.7,
      P<0.0001), lower BMI (21.5+/-3.8 vs 23.2+/-4.6, P<0.05), and greater cognitive
      impairment (8.4+/-2.6 vs 6.4+/-3.3, P<0.001) than those with EdFED scores under
      five. Using 5 points as the EdFED cutoff score, the prevalence rate of feeding
      difficulties was 60.2%. Using multiple regression to examine the predictors of
      feeding difficulty, 35.1% of the variance was explained, with ADL, cognition and
      number of medications being significant (beta = .46,.23 and .19, respectively),
      while non-significant factors were age, gender, duration of dementia and eating
      time. CONCLUSION: The prevalence of feeding difficulty was high among Taiwanese
      elderly with dementia. Training nurses or nursing assistants to notice feeding
      problems in order to provide adequate assistance is important for preventing
      malnutrition among residents with dementia in Taiwan nursing homes.

PMID- 22456784
TI  - The Alu polymorphism of angiotensin I converting enzyme (ACE) and
      atherosclerosis, incident chronic diseases and mortality in an elderly Chinese
      population.
AB  - OBJECTIVE: We examined the contribution of ACE I/D polymorphism in a large
      Chinese population to four year change in ankle-brachial index (ABI), development
      of cardiovascular diseases and mortality in a prospective study adjusting for
      many confounding factors. METHOD: Data are drawn from a longitudinal study of
      4000 community-living men and women aged 65 years and over, for which detailed
      information regarding lifestyle, chronic diseases, body mass index (BMI), ABI
      measurements and ACE polymorphisms were documented at baseline. During the fifth
      year of follow up, incident cardiovascular diseases, ABI, and mortality were
      documented, and related to ACE genotype adjusting for age, smoking, alcohol,
      dietary intake, physical activity, body mass index, and use of ACE inhibitors.
      RESULTS: Women with the D/D genotype had the greatest reduction in mean ABI after
      adjusting for confounding factors. D/D genotype was also more common among women
      who developed hypertension or myocardial infarction. However D/D genotype was
      associated with mortality only in men. CONCLUSION: In a Chinese elderly
      population, ACE polymorphism may be considered "deleterious" to longevity, the
      D/D genotype being associated with mortality, the atherosclerotic process,
      hypertension and myocardial infarction. There are gender differences in the
      relationship between D/D genotype and cardiovascular diseases and mortality may
      not be mediated by the atherosclerotic process alone.

PMID- 22456785
TI  - Vitamin D status in relation to postural stability in the elderly.
AB  - OBJECTIVES: Postural instability (PI) is an important risk factor for falls,
      especially in the frail older population. In this study, we investigated the
      impact of vitamin D deficiency on PI in a sample of community dwelling older
      subjects. Our objective was to determine the potential association between
      vitamin D deficiency and PI in older fallers. DESIGN: Cross-sectional study.
      SETTING: Falls and Fractures Clinic, Department of Geriatric Medicine, Nepean
      Hospital, Penrith, Australia. PARTICIPANTS: One hundred and forty-five adults
      aged 65 years and older who have had at least one episode of a fall within the
      six months prior to assessment at the Falls and Fractures Clinic. MEASUREMENTS:
      Serum 25(OH) vitamin D3 [25(OH)D3] and parathyroid hormone concentrations were
      determined at baseline. Subjects were separated into 3 groups based on serum
      25(OH)D3 levels with the following cut-off values: < 30 nmol/L (deficient), 30-50
      nmol/L (insufficient) and > 50 nmol/L (normal). Other baseline measurements
      included body mass index, mini-nutritional assessment, grip strength, serum
      calcium concentration and creatinine clearance, which were used as covariables.
      PI was assessed using a computerized virtual reality system (Medicaa, Uruguay).
      Measured parameters included limits of stability (LOS) and centre of pressure
      (COP) under eyes closed on foam (ECF) and visio-vestibular stimulation. The
      estimated swaying area, computed from the ellipse of confidence under eyes closed
      standing on foam (ECF), was also used as a PI parameter. Gait velocity (GV) was
      measured using a GaitRITE walkway system. RESULTS: Posture was impaired in
      vitamin D deficiency (<30 nmol/L) as indicated by lower LOS (90 +/- 18), higher
      ECF (25 +/- 10) and slower GV (55 +/- 7) as compared with the insufficient and
      normal groups. After adjustment for demographic, biochemical and anthropometric
      variables, vitamin D deficiency significantly correlated with low LOS and high
      COP under ECF. CONCLUSION: Low levels of vitamin D were associated with PI. This
      association could also have an effect on slow GV and increased risk of falls. In
      conclusion, using an objective method to measure balance in older fallers we have
      identified a novel role of vitamin D in balance control. Prospective studies are
      required to confirm the effect of vitamin D on PI and elucidate the mechanisms of
      this association.

PMID- 22456786
TI  - Vitamin B12 deficiency in Australian residential aged care facilities.
AB  - OBJECTIVE: To determine the prevalence of undiagnosed vitamin B12 deficiency
      among residential aged care facility residents in southern Tasmania, Australia,
      and to identify associated risk factors. DESIGN AND SETTING: Cross-sectional
      study of residents from five southern Tasmanian residential aged care facilities.
      PARTICIPANTS: Two hundred and fifty-nine residents without a prior diagnosis of
      vitamin B12 deficiency or recorded serum B12 level within the past 6 months were
      approached to have their serum B12 level tested. One hundred and sixty (61%)
      residents consented and their doctors were contacted for further consent. A total
      of 130 (50%) residents completed the study. MEASUREMENTS: Clinical and
      demographic characteristics, and serum B12 level. RESULTS: Of the 130 residents
      tested, 18 residents (14%) were considered vitamin B12 deficient (serum level
      <150 pmol/L), 47 (36%) were equivocal (150 pmol/L to 250 pmol/L) and 65 (50%) had
      normal serum B12 levels (>250 pmol/L). There was a weak negative correlation
      between age and serum B12 level in those residents not taking a multivitamin
      (n=120, r=-0.19, p<0.05). The use of a multivitamin or antipsychotic drug were
      associated with altered mean serum B12 levels (+137 pmol/L, p<0.001 and -70
      pmol/L, p<0.001 respectively). CONCLUSION: As vitamin B12 deficiency can manifest
      in a range of symptoms that are frequently misdiagnosed, the finding of
      undetected deficiency in 14% of residents is a cause for concern. Oral
      multivitamin supplementation may help prevent deficiency, and potentially treat
      existing deficiencies in older institutionalised people.

PMID- 22456787
TI  - BiClamp((r)) forceps was significantly superior to conventional suture ligation
      in radical abdominal hysterectomy: a retrospective cohort study in 391 cases.
AB  - OBJECTIVE: To evaluate the efficacy and security of ERBE BiClamp((r)) forceps in
      radical abdominal hysterectomy for managing those cervical cancers, extending to
      other gynecologic cancers such as endometrial cancer and ovarian cancer as well.
      METHODS: A retrospective cohort study was made in 391 cases from 450 FIGO IA2-IIB
      cervical cancers between November 2005 and September 2010. After baseline
      character analysis, the conventional group (n = 195) was compared with the
      BiClamp group (n = 196) on the basis of surgical outcome and complications. Data
      analysis was based on intention to treat with statistics software SPSS17.0.
      RESULTS: Comparison between conventional suture ligation and BiClamp((r)) forceps
      is as follows: the operation time was 247.7 +/- 47.7 min for the conventional
      suture ligation versus 224.1 +/- 36.2 min (P < 0.001) for BiClamp((r)) forceps,
      estimated blood loss was 769.2 +/- 310.4 ml versus 534.8 +/- 232.5 ml (P <
      0.001), gauze consumption was 35.3 +/- 10.6 sheets versus 28.2 +/- 7.4 sheets (P
      < 0.001), intra-operative blood transfusion rate was 75.9 versus 28.1% (P <
      0.001), hemoglobin decline was 29.2 +/- 10.1 g/L versus 26.5 +/- 9.2 g/L (P =
      0.085), postoperative blood transfusion rate was 17.0 versus 15.6% (P = 0.818),
      closed suction drainage was 268.8 +/- 162.0 ml versus 208.3 +/- 141.7 ml (P <
      0.001), hospital stay was 8.8 +/- 2.5 days versus 7.1 +/- 2.2 days (P < 0.001),
      postoperative complications was 23.6 versus 14.8% (P = 0.027). CONCLUSION: With
      obvious decrease of operation time, blood loss, postoperative complications,
      hospital stay and particularly, intra-operative blood transfusion rate,
      BiClamp((r)) forceps has been proved more efficient and controllable in radical
      abdominal hysterectomies of cervical cancers than conventional suture ligations,
      extending to endometrial cancers and ovarian cancers, hence deserves to be
      popularized.

PMID- 22456788
TI  - Temporal trends of latency period and perinatal survival after very early preterm
      premature rupture of fetal membranes.
AB  - PURPOSE: This paper shows temporal trends of latency period and perinatal
      survival after preterm premature rupture of membranes at or before 28 weeks (very
      early PPROM). METHODS: We have studied retrospectively medical records of all
      cases of very early PPROM attended in our Obstetric Department from January 1,
      2000 to December 31, 2010. RESULTS: A total of 327 cases of very early PPROM were
      attended, representing 0.4 % of all deliveries, 3.68 % of all preterm births and
      15 % of cases all of PPROM. The mean gestational age at delivery was 27 weeks
      (range 20-34). The mean duration of latency period for the total of 327 cases was
      12.1 days (range 0-83, SD 13.3), with a clear trend to its increase from 2005 (p
      < 0.05). The mean duration of latency period was largest in 2010 (p < 0.05). For
      the whole period 2000-2010, perinatal deaths reached 30.6 % of all cases, with a
      clear trend to decrease as gestational age at diagnosis increased, and over the
      years of study. We have also found a high rate of obstetric complications and a
      high rate of cesarean deliveries. CONCLUSIONS: The upward trend in the duration
      of latency period in all groups over the years of study and the encouraging
      perinatal survival observed, even in previable PPROM, are incentives to follow
      expectant/conservative management in these cases.

PMID- 22456789
TI  - Acute lobar nephronia in pregnancy: a rarely reported entity in obstetric renal
      medicine.

PMID- 22456793
TI  - Candida sirachaensis sp. nov. and Candida sakaeoensis sp. nov. two anamorphic
      yeast species from phylloplane in Thailand.
AB  - Three strains (LM008(T), LM068 and LM078(T)), representing two novel yeast
      species were isolated from the phylloplane of three plant species by an
      enrichment technique. On the basis of morphological, biochemical, physiological
      and chemotaxonomic characteristics, and the sequence analysis of the D1/D2 domain
      of the large subunit rRNA gene and the internal spacer region, the three strains
      were assigned as two novel Candida species. Strain LM008(T) was assigned to be
      Candida sirachaensis sp. nov. (type strain LM008(T) = BCC 47628(T) = NBRC
      108605(T) CBS 12094(T)) in the Starmerella clade. Two strains (LM068 and
      LM078(T)) represent a single species in the Lodderomyces-Spathaspora clade for
      which the name Candida sakaeoensis sp. nov. is proposed with the type strain
      LM078(T) = BCC 47632(T) = NBRC 108895(T) = CBS 12318(T).

PMID- 22456792
TI  - Janibacter alkaliphilus sp. nov., isolated from coral Anthogorgia sp.
AB  - A novel actinobacterium, designated strain SCSIO 10480(T), was isolated from a
      gorgonian coral sample of Anthogorgia sp. Phylogenetic and phenotypic properties
      of the organism supported that it belonged to the genus Janibacter. Phylogenetic
      analysis indicated that the levels of 16S rRNA gene sequence similarity between
      strain SCSIO 10480(T) and other type strains of recognized members of the genus
      Janibacter were 96.0-97.8 %. Growth in the presence of up to 17 % (w/v) NaCl and
      optimally at pH 9.0-10.0 was a distinctive characteristic of strain SCSIO
      10480(T). Other biochemical and physiological properties and the fatty acid
      profile also differentiated the isolate from other members of Janibacter species.
      Based on the results obtained in this study, we propose that strain SCSIO
      10480(T) should be classified within a novel species of the genus Janibacter, for
      which the name Janibacter alkaliphilus sp. nov. is proposed, with SCSIO 10480(T)
      (=CCTCC AB 2011027(T) = DSM 24723(T)) as the type strain.

PMID- 22456794
TI  - Investigation of LiAlH4-THF formation by direct hydrogenation of catalyzed Al and
      LiH.
AB  - The formation of LiAlH(4)-THF by direct hydrogenation of Al and LiH in
      tetrahydrofuran (THF) was investigated using spectroscopic and computational
      methods. The molecular structures and free energies of the various possible
      adducts (THF-AlH(3), THF-LiH and THF-LiAlH(4)) present in a LiAlH(4)/THF solution
      were calculated and the dominant species were determined to be contact ion pairs
      where three THF molecules coordinate the lithium. Raman and X-ray absorption
      spectroscopy were used to investigate the effect of different Ti precursors on
      the formation of Al-H species and LiAlH(4)-THF and determine the optimal reaction
      conditions. A unique sample stage was developed from a microfluidic cell to
      evaluate the catalysts in situ. The effectiveness of two types of catalysts,
      titanium chloride (TiCl(3)) and titanium butoxide (Ti(C(4)H(9)O)(4)), and the
      catalyst concentration were evaluated under similar reaction conditions. Both
      catalysts were effective at facilitating hydrogenation, although TiCl(3) was more
      effective over the first few cycles with the greatest kinetic enhancement
      achieved with a low concentration of around 0.15 mol%. These results were
      qualitatively supported by infrared spectroscopy, which indicated that although a
      small amount of Ti is necessary for disassociating H(2), excess surface Ti (>0.1
      ML) hinders the formation of Al-H species.

PMID- 22456795
TI  - Fish-hook injury of the eye.
AB  - The objective of this case report is to report two cases of fish-hook injury to
      the eye and ocular adnexa with review of literature. Both patients with fish-hook
      injuries were professional fishermen. The first subject was hit in his right eye
      by a hook which became embedded in the right cornea. He cut off the line but made
      no attempt to remove the hook and presented to the emergency department with the
      hook hanging from his right eye. Under general anaesthesia, the hook was rotated
      out without causing any further damage to the cornea and intraocular structures.
      The second subject was reeling the hook back to shore when it hit him in the face
      and embedded itself in the upper eyelid. He was immediately taken to the
      emergency department and after careful examination the eye was found to be
      unharmed and the hook was removed through a small incision under local
      anaesthesia. Fish-hook injuries, though rare, can result in visual morbidity. The
      hook should be removed under careful examination using the correct technique. The
      shaft of the hook should be left long and no attempt should be made by the
      subject or any non-trained person to remove it as doing so can result in further
      damage.

PMID- 22456797
TI  - A convenient biomimetic synthesis of optically active putative neurotoxic
      metabolites of MDMA ("ecstasy") from R-(-)- and S-(+)-N-methyl-alpha
      methyldopamine precursors.
AB  - (+/-)-3,4-Methylenedioxymethamphetamine (MDMA, also known as "ecstasy") is a
      psychoactive drug with selective neurotoxic potential toward brain serotonin (5
      HT) neurons. One hypothesis holds that MDMA neurotoxicity may at least partially
      be a consequence of its metabolism. In most species (including primates), O
      demethylenated MDMA metabolites such as N-methyl-alpha-methyldopamine (HHMA) have
      been postulated to serve as precursors for toxic thioether conjugates. As yet,
      chirality of MDMA was not considered in previously reported in vivo studies
      because HHMA was used as the racemate. Since the stereochemistry of this chiral
      drug needs to be considered, the total synthesis of enantiomerically pure
      precursors, R-(-)-HHMA and S-(+)-HHMA, was envisioned with the ultimate goal to
      prepare substantial amounts of optically active thioether conjugates. Recently,
      we reported the first total synthesis of the R-enantiomer. In this paper, a novel
      synthesis of the S-enantiomer is described, in 45% overall yield (six steps) and
      99% ee, using commercially available l-Boc-alanine (99% ee) as the chiral source.
      Having at our disposal suitable amounts of R-(-)-HHMA and S-(+)-HHMA precursors,
      a straightforward one-pot electrochemical procedure has been further developed
      for the synthesis of several catechol-thioether conjugates in acceptable yields
      (40-53%) and high degree of purity (99%), with complete diastereoselectivity. The
      availability of these newly synthesized optically active catechol-thioether
      conjugates is crucial for ongoing future in vivo studies about their role in MDMA
      neurotoxicity.

PMID- 22456798
TI  - A programmable microfluidic cell array for combinatorial drug screening.
AB  - We describe the development of a fully automatic and programmable microfluidic
      cell culture array that integrates on-chip generation of drug concentrations and
      pair-wise combinations with parallel culture of cells for drug candidate
      screening applications. The device has 64 individually addressable cell culture
      chambers in which cells can be cultured and exposed either sequentially or
      simultaneously to 64 pair-wise concentration combinations of two drugs. For
      sequential exposure, a simple microfluidic diffusive mixer is used to generate
      different concentrations of drugs from two inputs. For generation of 64 pair-wise
      combinations from two drug inputs, a novel time dependent variable concentration
      scheme is used in conjunction with the simple diffusive mixer to generate the
      desired combinations without the need for complex multi-layer structures or
      continuous medium perfusion. The generation of drug combinations and exposure to
      specific cell culture chambers are controlled using a LabVIEW interface capable
      of automatically running a multi-day drug screening experiment. Our cell array
      does not require continuous perfusion for keeping cells exposed to concentration
      gradients, minimizing the amount of drug used per experiment, and cells cultured
      in the chamber are not exposed to significant shear stress continuously. The
      utility of this platform is demonstrated for inducing loss of viability of PC3
      prostate cancer cells using combinations of either doxorubicin or mitoxantrone
      with TRAIL (TNF-alpha Related Apoptosis Inducing Ligand) either in a sequential
      or simultaneous format. Our results demonstrate that the device can capture the
      synergy between different sensitizer drugs and TRAIL and demonstrate the
      potential of the microfluidic cell array for screening and optimizing
      combinatorial drug treatments for cancer therapy.

PMID- 22456799
TI  - Neurological recovery in patients of old healed tubercular rigid kyphosis with
      myelopathy treated with transpedicular decancellation osteotomy.
AB  - PURPOSE: The purpose of the study was to find out if transpedicular
      decancellation osteotomy (TDO) is recommendable for neurological recovery in
      patients with myelopathy due to tubercular rigid kyphosis. We have analyzed the
      pattern of recovery seen after the surgery and also made an effort to correlate
      the neurological recovery with preoperative clinical and radiological features.
      METHODS: The clinical parameters used were (1) ASIA impairment scale for motor
      and sensory function, (2) sphincter dysfunction score, (3) time duration from the
      onset of myelopathy till the date of surgery, and (4) SRS 30 outcomes
      questionnaire. Radiological parameters used were (1) Cobb's angle in
      standing/sitting radiographs, (2) levels of gibbus, (3) cord changes in sagittal
      T2 MRI images, and (4) percentage of cord compression. Assessment was done
      preoperatively and at 1 month, 3 months, 6 months, 1 year and at 2 years
      postoperatively. RESULTS: Seventeen patients were included. The follow-up period
      was 2 years. We had one patient in ASIA A, nine patients in ASIA C and seven
      patients in ASIA D. Four patients with ASIA C presented with mild sphincter
      disturbance (score 2) and one presented with severe disturbance (score 1). The
      ASIA A patient had complete retention (score 0). The ASIA impairment scale
      improved after surgery, with maximum improvement at 3 months and improvement
      continuing up to 6 months. 16 (94 %) patients had improvement in lower limb
      function and 5 (83 %) patients had improvement of sphincter function. 94 %
      patients had neurological recovery after the operation. The neurological recovery
      reached a plateau at 6 months with no significant improvement in the further
      follow-up. Preoperative MRI changes, cord compression and duration from onset of
      myelopathy to day of surgery were not predictive of the final neurological
      outcome after surgery. CONCLUSION: TDO gives good results in delayed onset
      neurological deficits in caries spine with rigid kyphosis. At least, one grade
      improvement in the neurological status of patients with ASIA C and ASIA D can be
      expected. Maximum improvement in the neurology is seen in the first 3 months and
      up to 6 months from the date of surgery, without much improvement thereafter.
      Level of evidence Level IV.

PMID- 22456800
TI  - Factors affecting shoulder-pelvic integration during axial trunk rotation in
      subjects with recurrent low back pain.
AB  - INTRODUCTION: Shoulder-pelvic integration could play a central role in the
      control of dynamic posture and movement. However, kinematic coordination during
      axial trunk rotation has not been carefully investigated in subjects with
      recurrent low back pain (LBP). The purpose of this study was to compare the
      maximum rotational angles of the shoulders and pelvis in the transverse plane
      between subjects with and without recurrent LBP. MATERIALS AND METHODS: A total
      of 38 age-matched subjects (19 control subjects: 69.00 +/- 5.75 years old and 19
      subjects with LBP: 68.79 +/- 5.40 years old) participated in the study. The axial
      trunk rotation test was conducted in the upright position with bilateral hips and
      knees fully extended and both feet shoulder width apart. RESULTS: The results of
      this study indicated that there was a difference in pelvic girdle rotation
      between groups (100.79 +/- 26.46 in the control group, 82.12 +/- 23.16 in the LBP
      group; t = 2.31, p = 0.02); however, there was no difference for the shoulder
      girdle (177.63 +/- 36.98 in the control group, 156.42 +/- 30.09 in the LBP group;
      t = 1.91, p = 0.06). There were interactions with age (F = 9.27, p = 0.004) and
      BMI (F = 7.50, p = 0.01) with the rotational angles of the shoulder and pelvis.
      CONCLUSION: These results indicated a different pattern of trunk rotation
      movement with the age and BMI serving as important factors to consider for
      recurrent LBP. The results of our study also indicated a different pattern of
      shoulder and pelvic coordination with age and gender. Clinicians need to consider
      the consequences of limited shoulder-pelvic rotational angles, especially limited
      rotational angle on the pelvis during trunk axial rotation. Further studies are
      required to determine the causes of the underlying problems for clinical decision
      making and altered shoulder-pelvic rotation in subjects with recurrent LBP.

PMID- 22456802
TI  - Prolonged portal triad clamping increases postoperative sepsis after major
      hepatectomy in patients with sinusoidal obstruction syndrome and/or
      steatohepatitis.
AB  - BACKGROUND: Portal triad clamping (PTC) has been widely adopted in an attempt to
      decrease bleeding during liver parenchymal transection. As a larger proportion of
      patients are treated with chemotherapy prior to liver resection, the safety of
      PTC in patients with chemotherapy-associated liver injury remains poorly
      investigated. This study aims to evaluate the influence of PTC on early
      postoperative outcomes in patients with chemotherapy-associated liver injury
      undergoing major hepatectomy for colorectal liver metastases (CLM). PATIENTS AND
      METHODS: From January 2000 to October 2010, 53 patients with histologically
      proven chemotherapy-associated liver injuries [sinusoidal obstruction syndrome
      (SOS; n = 41), steatohepatitis (n = 5), and both SOS and steatohepatitis (n = 7)]
      who underwent major hepatectomy for CLM were divided into two groups; patients
      undergoing intermittent TPC (n = 20) and those who did not undergo TPC (n = 33).
      Perioperative clinicobiological factors, morbidity including septic
      complications, and mortality were analyzed and compared between the two groups.
      RESULTS: Intraoperative blood transfusions and postoperative liver function were
      comparable between the two groups. Sepsis and biloma occurred more often in
      patients undergoing PTC longer than 30 min than in those undergoing PTC <= 30 min
      (66.7 % versus 17.1 %, p = 0.002, and 33.3 versus 0 %, p = 0.002, respectively).
      A multiple logistic regression analysis showed that prolonged PTC (>30 min) and
      the ratio of future liver remnant volume to total liver volume <= 43 % were
      independent factors for predicting postoperative sepsis [odds ratio (OR): 32.68;
      95 % confidence interval (95 % CI): 2.86-372.82; p = 0.005--and odds ratio: 9.70;
      95 % CI: 1.04-90.86; p = 0.047, respectively]. CONCLUSIONS: Portal triad clamping
      can be safely used in patients with chemotherapy-associated liver injury who
      require major liver resection. Prolonged PTC can increase the occurrence of
      postoperative biliary and septic complications.

PMID- 22456796
TI  - A single-nucleotide polymorphism in ANK1 is associated with susceptibility to
      type 2 diabetes in Japanese populations.
AB  - To identify a novel susceptibility locus for type 2 diabetes, we performed an
      imputation-based, genome-wide association study (GWAS) in a Japanese population
      using newly obtained imputed-genotype data for 2 229 890 single-nucleotide
      polymorphisms (SNPs) estimated from previously reported, directly genotyped GWAS
      data in the same samples (stage 1: 4470 type 2 diabetes versus 3071 controls). We
      directly genotyped 43 new SNPs with P-values of <10(-4) in a part of stage-1
      samples (2692 type 2 diabetes versus 3071 controls), and the associations of
      validated SNPs were evaluated in another 11 139 Japanese individuals (stage 2:
      7605 type 2 diabetes versus 3534 controls). Combined meta-analysis using directly
      genotyped data for stages 1 and 2 revealed that rs515071 in ANK1 and rs7656416
      near MGC21675 were associated with type 2 diabetes in the Japanese population at
      the genome-wide significant level (P < 5 * 10(-8)). The association of rs515071
      was also observed in European GWAS data (combined P for all populations = 6.14 *
      10(-10)). Rs7656416 was in linkage disequilibrium to rs6815464, which had
      recently been identified as a top signal in a meta-analysis of East Asian GWAS
      for type 2 diabetes (r(2) = 0.76 in stage 2). The association of rs7656416 with
      type 2 diabetes disappeared after conditioning on rs6815464. These results
      indicate that the ANK1 locus is a new, common susceptibility locus for type 2
      diabetes across different ethnic groups. The signal of association was weaker in
      the directly genotyped data, so the improvement in signal indicates the
      importance of imputation in this particular case.

PMID- 22456803
TI  - Role of antibiotic therapy in mild acute calculus cholecystitis: a prospective
      randomized controlled trial.
AB  - BACKGROUND: Current recommendations for treating acute calculus cholecystitis
      include the use of intravenous antibiotics, although these recommendations were
      never tested scientifically. The aim of this study was to evaluate the role of
      intravenous antibiotic therapy in patients with mild acute calculus
      cholecystitis. METHODS: In this prospective, randomized controlled trial, 84
      patients with a diagnosis of mild acute calculus cholecystitis were randomly
      assigned to supportive treatment only or supportive treatment with intravenous
      antibiotic treatment (42 patients in each arm). Patients were followed through
      their index admission and until delayed laparoscopic cholecystectomy was
      performed. RESULTS: The two study groups did not differ in their demographic data
      or in the clinical presentation and disease severity. Analysis was conducted on
      the intent-to-treat basis. Patients in the intravenous antibiotics arm resumed a
      liquid diet earlier (1.7 vs. 2.2 days, p = 0.02) but did not significantly differ
      in resumption of regular diet (2.8 vs. 3.2 days, p = 0.16) or hospital length of
      stay (LOS) (3.9 vs. 3.8 days, p = 0.89). Patients in the intravenous antibiotics
      arm had rates of percutaneous cholecystostomy tube placement (12 vs. 5 %, p =
      0.43), readmissions (19 vs. 13 %, p = 0.73), and perioperative course similar to
      those not receiving antibiotics. The overall hospital LOS, including initial
      hospitalization and subsequent cholecystectomy, was similar for both groups (5.6
      vs. 5.1 days, p = 0.29). Eight (19 %) patients in the supportive arm were crossed
      over to the intravenous antibiotic arm during the index admission. CONCLUSIONS:
      Intravenous antibiotic treatment does not improve the hospital course or early
      outcome in most of the patients with mild acute calculus cholecystitis.

PMID- 22456806
TI  - Validity and reliability of the Turkish version of the Pelvic Floor Distress
      Inventory-20.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to investigate the
      reliability and validity of the Turkish version of the Pelvic Floor Distress
      Inventory-20 (PFDI-20). METHODS: One hundred and twenty-eight women with pelvic
      floor disorders, including pelvic organ prolapse, urinary incontinence, and anal
      incontinence were enrolled in the study. The Turkish version was developed using
      forward back translation. Construct validity was examined by correlation of
      clinical methods. Interclass correlation coefficients (ICC) compared the PFDI-20
      and subscale scores. Cronbach's alpha assessed the internal consistency of the
      Turkish version. RESULTS: The PFDI-20 has three subscales. The test-retest
      reliability of the PFDI-20 and subscale was excellent (ICC 0.96 to 0.98, p <
      0.001). Cronbach's alpha value (0.79) was moderate for the PFDI-20. Construct
      validity demonstrated that the PFDI-20 and each subscale displayed significant
      correlation with other clinical methods used (p < 0.05). CONCLUSIONS: The PFDI-20
      is a valid and reliable condition-specific questionnaire for Turkish women with
      pelvic floor disorders.

PMID- 22456810
TI  - MRI assessment of internal acoustic canal variations using 3D-FIESTA sequences.
AB  - Magnetic resonance imaging (MRI) of the internal acoustic canal is the standard
      diagnostic tool for a wide range of indications in patients. This study aims to
      investigate the vascular variations and compression of the cranial nerves (CNs)
      VII and VIII at the cerebellopontine angle in patients with neuro-otologic
      symptoms using 3D-fast imaging employing steady-state acquisition (FIESTA) MR
      imaging. One hundred and eighty-seven patients (374 temporal bones) were examined
      on a 1.5-T MRI. In addition to conventional MR sequences, a 3D-FIESTA MR imaging
      was acquired. Magnetic resonance images thus obtained were evaluated with special
      regard to the presence of vascular contact to the CNs VII and VIII, as well as
      the presence of the vascular variations of the anterior inferior cerebellar
      artery (AICA) causing the compression of CNs. The Chi-squared test was used for
      statistical analysis. No statistically significant differences were found between
      the presence and absence of the AICA loop and/or vascular contact for the
      clinical symptoms of patients (P > 0.05). The cisternal and canalicular segments
      of CNs VII and VIII and adjacent vascular variations are well identified using 3D
      FIESTA, especially by determining the relationship of the AICA variations between
      CNs.

PMID- 22456805
TI  - Injectable biomaterials for adipose tissue engineering.
AB  - Adipose tissue engineering has recently gained significant attention from
      materials scientists as a result of the exponential growth of soft tissue filler
      procedures being performed within the clinic. While several injectable materials
      are currently being marketed for filling subcutaneous voids, they often face
      limited longevity due to rapid resorption. Their inability to encourage natural
      adipose formation or ingrowth necessitates repeated injections for a prolonged
      effect and thus classifies them as temporary fillers. As a result, a significant
      need for injectable materials that not only act as fillers but also promote in
      vivo adipogenesis is beginning to be realized. This paper will discuss the
      advantages and disadvantages of commercially available soft tissue fillers. It
      will then summarize the current state of research using injectable synthetic
      materials, biopolymers and extracellular matrix-derived materials for adipose
      tissue engineering. Furthermore, the successful attributes observed across each
      of these materials will be outlined along with a discussion of the current
      difficulties and future directions for adipose tissue engineering.

PMID- 22456811
TI  - Overview of a classical biological control project directed against the red palm
      mite in Florida.
AB  - Information is provided on the steps involved in classical biological control
      programs, with an outline of the steps achieved in the classical biological
      control of the red palm mite, Raoiella indica (Acari: Tenuipalpidae), in Florida.
      An overview is provided of the results and an accompanying paper by Bowman and
      Hoy (2012) describes the molecular analyses conducted to characterize phytoseiid
      predators of the red palm mite collected from Mauritius. The Mauritius
      phytoseiids were identified as Amblyseius largoensis, using morphological
      criteria, and compared to four populations of A. largoensis from Florida. The
      difficulties encountered in the systematics, rearing, and evaluation of the
      Mauritius phytoseiids are described. A method was tested for obtaining DNA from
      single mites without destroying the body so that voucher specimens can be
      maintained. Ultimately, the project was terminated due to constraints expected in
      obtaining permission to make releases.

PMID- 22456812
TI  - Obtaining molecular data for all life stages of Typhlodromus (Typhlodromus)
      exhilaratus (Mesostigmata: Phytoseiidae): consequences for species
      identification.
AB  - Several species of the family Phytoseiidae are known to control mite pests in
      many crops worldwide. However, biological control success greatly depends on the
      accurate identification of these predatory mites. Species diagnostics is
      essentially based on the morphological characters of females. Thus, when only
      immature stages and/or males are collected, their identification is poorly
      supported. Molecular tools could be of great help to overcome these difficulties,
      as molecular sequences are assumed to be identical for the life stage considered.
      However, one of the essential points is to extract a sufficient DNA amount from a
      single specimen of immature stages (eggs, protonymphs, deutonymphs) and males
      (less than 300 MUm in length) to amplify and sequence DNA. The markers used were
      two mitochondrial DNA fragments (12S rRNA and Cytb mtDNA) and the species studied
      were Typhlodromus (Typhlodromus) exhilaratus and T. (T.) phialatus, two cryptic
      species, reported to control mite pests in crops of southern Europe and commonly
      found on the same plants. Despite a low quantity of DNA extracted, particularly
      for the egg, larva and protonymph stages, DNA was amplified and sequences were
      obtained from all the life stages considered with the two mtDNA fragments.
      Sequences from all the developmental stages of T. (T.) exhilaratus were identical
      and well differentiated from those of its sister-species. However, contaminations
      were observed especially for eggs and DNA amplified with the Cytb mt marker.
      Utility of the present results are discussed and protocol improvements are
      proposed.

PMID- 22456813
TI  - Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a
      mouse model of pleurisy: evidence for the role of adenosine A2 receptors.
AB  - Adenosine and its metabolite, inosine, have been described as molecules that
      participate in regulation of inflammatory response. The aim of this study was to
      investigate the effect of adenosine and inosine in a mouse model of carrageenan
      induced pleurisy as well as the participation of adenosine receptors in this
      response. Injection of carrageenan into the pleural cavity induced an acute
      inflammatory response characterized by leukocyte migration, pleural exudation,
      and increased release of interleukin-1beta and tumor necrosis factor-alpha in
      pleural exudates. The treatment with adenosine (0.3-100 mg/kg, i.p.) and inosine
      (0.1-300 mg/kg, i.p.) 30 min before carrageenan injection reduced significantly
      all these parameters analyzed. Our results also demonstrated that A(2A) and A(2B)
      receptors seem to mediate the adenosine and inosine effects observed, since
      pretreatment with selective antagonists of adenosine A(2A) (ZM241385) and A(2B)
      (alloxazine) receptors, reverted the inhibitory effects of adenosine and inosine
      in pleural inflammation. The involvement of A(2) receptors was reinforced with
      adenosine receptor agonist CGS21680 treatment, since its anti-inflammatory
      effects were reversed completely and partially with ZM241385 and alloxazine
      injection, respectively. Moreover, the combined treatment with subeffective dose
      of adenosine (0.3 mg/kg) and inosine (1.0 mg/kg) induced a synergistic anti
      inflammatory effect. Thus, based on these findings, we propose that inosine
      contributes with adenosine to exert anti-inflammatory effects in pleural
      inflammation, reinforcing the notion that endogenous nucleosides play an
      important role in controlling inflammatory diseases. This effect is likely
      mediated by the activation of adenosine A(2) subtype receptors and inhibition of
      production or release of pro-inflammatory cytokines.

PMID- 22456815
TI  - Cognitive flexibility in ASD; task switching with emotional faces.
AB  - Children with autism spectrum disorders (ASDs) show daily cognitive flexibility
      deficits, but laboratory data are unconvincing. The current study aimed to bridge
      this gap. Thirty-one children with ASD (8-12 years) and 31 age- and IQ-matched
      typically developing children performed a gender emotion switch task. Unannounced
      switches and complex stimuli (emotional faces) improved ecological validity;
      minimal working memory-load prevented bias in the findings. Overall performance
      did not differ between groups, but in a part of the ASD group performance was
      slow and inaccurate. Moreover, within the ASD group switching from emotion to
      gender trials was slower than vice versa. Children with ASD do not show
      difficulties on an ecological valid switch task, but have difficulty disengaging
      from an emotional task set.

PMID- 22456816
TI  - The implications of social neuroscience for social disability.
AB  - Social disability represents a unifying feature in the diverse group of
      individuals with autism spectrum disorder (ASD). Social neuroscience is the study
      of brain mechanisms supporting interpersonal interaction. In this paper, we
      review brain imaging studies of the social brain and highlight practical
      applications of these scientific insights. Understanding of social brain
      mechanisms holds promise as a tool for defining meaningful subgroups of children
      with ASD to facilitate genetic analyses and to inform treatment selection.
      Because social brain systems emerge in infancy, social neuroscience may help to
      detect atypical development before symptoms manifest. This conceptualization of
      ASD is a hopeful one, as social brain systems remain malleable well into
      development and are thus amenable to targeted intervention.

PMID- 22456817
TI  - Atypical social referencing in infant siblings of children with autism spectrum
      disorders.
AB  - Social referencing was investigated in 18-month-old siblings of children with
      autism spectrum disorders (ASD; "high-risk infants"). Infants were exposed to
      novel toys, which were emotionally tagged via adults' facial and vocal signals.
      Infants' information seeking (initiation of joint attention with an adult) and
      their approach/withdrawal behavior toward the toys before versus after the
      adults' emotional signals was measured. Compared to both typically developing
      infants and high-risk infants without ASD, infants later diagnosed with ASD
      engaged in slower information seeking, suggesting that this aspect of referencing
      may be an early indicator of ASD. High-risk infants, both those who were and
      those who were not later diagnosed with ASD, exhibited impairments in regulating
      their behavior based on the adults' emotional signals, suggesting that this
      aspect of social referencing may reflect an endophenotype for ASD.

PMID- 22456818
TI  - Use of audio cuing to expand employment opportunities for adolescents with autism
      spectrum disorders and intellectual disabilities.
AB  - We evaluated audio cuing to facilitate community employment of individuals with
      autism and intellectual disability. The job required promoting products in retail
      stores by wearing an air-inflated WalkAround(r) costume of a popular commercial
      character. Three adolescents, ages 16-18, were initially trained with video
      modeling. Audio cuing was then used by an attendant who delivered prompts
      regarding when to perform job skills. The two interventions were evaluated in an
      interrupted time series withdrawal design during training and then again in an
      actual job setting. Results show video modeling was not effective. However, the
      audio cuing produced job performances well above the designated criteria during
      training and when on the job. These changes were replicated with each
      participant, demonstrating clear experimental control. The changes proved
      statistically significant as well. Participants and parents reported high job
      satisfaction. The challenges of competitive employment for individuals with
      autism and intellectual disabilities are discussed.

PMID- 22456819
TI  - Understanding parent-child social informant discrepancy in youth with high
      functioning autism spectrum disorders.
AB  - We investigated discrepancies between parent- and self-reported social
      functioning among youth with autism spectrum disorders (ASD). Three distinct
      samples showed discrepancies indicating that parents viewed their children as
      performing one standard deviation below a standardization mean, while youth
      viewed themselves as comparably-skilled relative to peers. Discrepancies
      predicted lower parental self-efficacy, and lower youth-reported hostile
      attributions to peers, marginally-lower depression, and decreased post-treatment
      social anxiety. Discrepancies predicted outcomes better than parent- or youth
      report alone. Informant discrepancies may provide valuable additional information
      regarding child psychopathology, parental perceptions of parenting stress, and
      youth treatment response. Findings support a model where abnormal self
      perceptions in ASD stem from inflated imputation of subjective experiences to
      others, and provide direction for improving interventions for youth and parents.

PMID- 22456820
TI  - Are prenatal ultrasound scans associated with the autism phenotype? Follow-up of
      a randomised controlled trial.
AB  - An existing randomised controlled trial was used to investigate whether multiple
      ultrasound scans may be associated with the autism phenotype. From 2,834 single
      pregnancies, 1,415 were selected at random to receive ultrasound imaging and
      continuous wave Doppler flow studies at five points throughout pregnancy
      (Intensive) and 1,419 to receive a single imaging scan at 18 weeks (Regular),
      with further scans only as indicated on clinical grounds. There was no
      significant difference in the rate of Autism Spectrum Disorder between the
      Regular (9/1,125, 0.8 %) and Intensive (7/1,167, 0.6 %) groups, nor a difference
      between groups in the level of autistic-like traits in early adulthood. There is
      no clear link between the frequency and timing of prenatal ultrasound scans and
      the autism phenotype.

PMID- 22456823
TI  - Reduced amygdala response in youths with disruptive behavior disorders and
      psychopathic traits: decreased emotional response versus increased top-down
      attention to nonemotional features.
AB  - OBJECTIVE: Amygdala dysfunction has been reported to exist in youths and adults
      with psychopathic traits. However, there has been disagreement as to whether this
      dysfunction reflects a primary emotional deficit or is secondary to atypical
      attentional control. The authors examined the validity of the contrasting
      predictions. METHOD: Participants were 15 children and adolescents (ages 10-17
      years) with both disruptive behavior disorders and psychopathic traits and 17
      healthy comparison youths. Functional MRI was used to assess the response of the
      amygdala and regions implicated in top-down attentional control (the dorsomedial
      and lateral frontal cortices) to emotional expression under conditions of high
      and low attentional load. RESULTS: Relative to youths with disruptive behavior
      disorders and psychopathic traits, healthy comparison subjects showed a
      significantly greater increase in the typical amygdala response to fearful
      expressions under low relative to high attentional load conditions. There was
      also a selective inverse relationship between the response to fearful expressions
      under low attentional load and the callous-unemotional component (but not the
      narcissism or impulsivity component) of psychopathic traits. In contrast, the two
      groups did not differ in the significant recruitment of the dorsomedial and
      lateral frontal cortices as a function of attentional load. CONCLUSIONS: Youths
      with disruptive behavior disorders and psychopathic traits showed reduced
      amygdala responses to fearful expressions under low attentional load but no
      indications of increased recruitment of regions implicated in top-down
      attentional control. These findings suggest that the emotional deficit observed
      in youths with disruptive behavior disorders and psychopathic traits is primary
      and not secondary to increased top-down attention to nonemotional stimulus
      features.

PMID- 22456826
TI  - Low temperature activation and reactivity of CO2 over a Cr(II)-based
      heterogeneous catalyst: a spectroscopic study.
AB  - A new heterogeneous catalyst for CO(2) activation was identified in the
      Cr(II)/SiO(2) Phillips catalyst, one of the most important catalysts used
      industrially for olefin polymerization. Interestingly, it was found that
      Cr(II)/SiO(2) strongly activates CO(2) already at room temperature, making it
      available for chemicals synthesis. A preliminary attempt in this direction was
      done by following the reaction of CO(2) with ethylene oxide at room temperature
      by means of FT-IR spectroscopy, which showed the formation of ethylene carbonate.
      Besides non-reductive CO(2) activation, Cr(II)/SiO(2) showed good performances in
      catalytic reduction of CO(2) to CO, when heated under mild conditions or
      irradiated with UV-Vis light. Both, in situ FT-IR and UV-Vis spectroscopy, were
      applied to highlight the redox process occurring at the Cr centres. These results
      open interesting perspectives to be developed in the field of CO(2) chemical
      fixation.

PMID- 22456827
TI  - Positive regulatory dynamics by a small noncoding RNA: speeding up responses
      under temperature stress.
AB  - Recent discoveries of noncoding regulatory RNAs have led to further understanding
      of the elements controlling genetic expression. In E. coli, most of those ncRNAs
      for which functional knowledge is available were shown to be dependent on the Hfq
      RNA chaperone and to act as inhibitors of translation by base pairing with their
      mRNA target. Nevertheless, there are also some examples where the sRNA plays a
      role of a translational activator, structurally enhancing ribosome binding to
      mRNA. In this work, we seek to understand the dynamics of DsrA-based positive
      regulation of rpoS mRNA, encoding the sigma(S) RNA polymerase subunit, and to
      understand how it helps to mitigate environmental stress in bacteria. Our
      analysis is based on the first absolute quantification of the copy number of both
      the sRNA and of its corresponding mRNA in combination with mathematical models
      for post-transcriptional regulation. We show that on average, DsrA is present at
      a ratio of 3 to 24 copies per cell, while an rpoS transcript is present at a
      level of 1 to 4 copies per cell, both levels increasing when temperature is
      decreased. Our analysis supports the idea that temperature dependency of DsrA
      degradation is not a crucial condition for the attainment of observed DsrA steady
      levels, but highlights that this may have a marked influence on the dynamics of
      the regulation, notably to speed up the time of recovery to normal RNA levels
      after ending the stress signal. Further, our analysis also reveals how
      reversibility of RNA complex formation and sigma(S)-regulated degradation act to
      reduce intrinsic noise in sigma(S) induction. Taking into account the importance
      of this master regulator, which allows E. coli as well as other important
      pathogens to survive their environment, the present work contributes to complete
      the panel of multiple signals used to regulate bacterial transcription.

PMID- 22456825
TI  - Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y
      chromosome in 1,306 infertile Korean men.
AB  - OBJECTIVES: To determine the prevalence of Y chromosome microdeletions in
      infertile Korean men with abnormal sperm counts and to assess the clinical
      features and frequency of chromosomal abnormalities in Korean patients with
      microdeletions. METHODS: A total of 1,306 infertile men were screened for Y
      chromosome microdeletions, and 101 of them had microdeletions. These 101 men were
      then retrospectively studied for cytogenetic evaluation, testicular biopsy and
      outcomes of IVF and ICSI. RESULTS: The overall prevalence of Y chromosome
      microdeletions in infertile men was 7.7% (101/1,306). Most microdeletions were in
      the AZFc region (87.1%), including deletions of AZFbc (24.7%) and AZFabc (8.9%).
      All patients with AZFa, AZFbc and AZFabc deletions had azoospermia, whereas
      patients with an AZFc deletion usually had low levels of sperm in the ejaculate
      or in the testis tissues. Chromosomal studies were performed in 99 men with
      microdeletions, 36 (36.4%) of whom had chromosomal abnormalities. Among the
      infertile men with Y chromosome microdeletions in this study, the incidence of
      chromosomal abnormality was 48.6% in the azoospermic group and 3.7% in the
      oligozoospermic group. Among the 69 patients with microdeletions and available
      histological results, 100.0% of the azoospermic group and 85.7% of the
      oligozoospermic group had histological abnormalities. The frequency of both
      chromosomal abnormalities and histological abnormalities was higher in the
      azoospermic group compared to the oligozoospermic group. Thirty-four ICSI cycles
      with either testicular (n = 14) or ejaculated spermatozoa (n = 20) were performed
      in 23 couples with men with AZFc microdeletion. Thirteen clinical pregnancies
      (39.4%) were obtained, leading to the birth of 13 babies. CONCLUSIONS: The study
      results revealed a close relationship between microdeletions and spermatogenesis,
      although IVF outcome was not significantly affected by the presence of the AZFc
      microdeletion. Nevertheless, Y chromosome microdeletions have the potential risk
      of being transmitted from infertile fathers to their offspring by ICSI.
      Therefore, before using ICSI in infertile patients with severe spermatogenic
      defects, careful evaluations of chromosomal abnormalities and Y chromosome
      microdeletions screening should be performed and genetic counseling should be
      provided before IVF-ET.

PMID- 22456828
TI  - Second-order many-body perturbation study of solid hydrogen fluoride under
      pressure.
AB  - A linear-scaling, embedded-fragment, second-order many-body perturbation (MP2)
      method with basis sets up to aug-cc-pVTZ is applied to the antiparallel structure
      of solid hydrogen fluoride and deuterium fluoride under 0-20 GPa of ambient
      pressure. The optimized structures, including the lattice parameters and molar
      volume, and phonon dispersion as well as phonon density of states (DOS), are
      determined as a function of pressure. The basis-set superposition errors are
      removed by the counterpoise correction. The structural parameters at 0 GPa
      calculated by MP2 agree accurately with the observed, making the predicted values
      at higher pressures a useful pilot for future experiments. The corresponding
      values obtained by the Hartree-Fock method have large, systematic errors. The
      MP2/aug-cc-pVDZ frequencies of the infrared- and Raman-active vibrations of the
      three-dimensional solids are in good agreement with the observed and also justify
      previous vibrational analyses based on one-dimensional chain models; the non
      coincidence of the infrared and Raman mode pairs can be explained as factor-group
      (Davydov) splitting. The exceptions are one pair of modes in the librational
      region, for which band assignments based on a one-dimensional chain model need to
      be revised, as well as the five pseudo-translational modes that exist only in a
      three-dimensional treatment. The observed pressure dependence of Raman bands in
      the stretching region, which red-shift with pressure, is accounted for by theory
      only qualitatively, while that in the pseudo-translational region is reproduced
      with quantitative accuracy. The present calculation proves to be limited in
      explaining the complex pressure dependence of the librational modes. The hydrogen
      amplitude-weighted phonon DOS at 0 GPa is much less structured than the DOS
      obtained from one-dimensional models and may be more realistic in view of the
      also broad, structureless observed inelastic neutron scattering spectra. All
      major observed peaks can be straightforwardly assigned to the calculated peaks in
      the DOS. With increasing pressure, MP2 predicts further broadening of bands and
      breach of the demarcation between the pseudo-translational and librational bands.

PMID- 22456829
TI  - Catalytic activity of nanoalloys from gold and palladium.
AB  - We present a quantitative study of the catalytic activity of well-defined faceted
      gold-palladium nanoalloys which are immobilized on cationic spherical
      polyelectrolyte brushes. The spherical polyelectrolyte brush particles used as
      carriers for the nanoalloys consist of a solid polystyrene core onto which
      cationic polyelectrolyte chains of 2-aminoethyl methacrylate are attached. Au/Pd
      nanoalloy particles with sizes in the range from 1 to 3 nm have been generated
      which are homogeneously distributed on the surface of the spherical
      polyelectrolyte brushes. The reduction of 4-nitrophenol has been chosen as a well
      controlled model reaction allowing us to determine the catalytic activity of the
      nanoalloys as a function of the Au/Pd composition. The adsorption behavior was
      studied by Langmuir-Hinshelwood kinetics. We find a pronounced maximum of the
      catalytic activity at 75 molar % Au. A comparison of gold, platinum, palladium
      and gold-palladium alloy nanoparticles is made in terms of Langmuir-Hinshelwood
      kinetics. Density functional calculations for Au/Pd clusters with up to 38 atoms
      show that the density of states at the Fermi level increases with increasing Pd
      content, and that the highest occupied orbitals are associated with Pd atoms. The
      calculations confirm that small changes in the atomic arrangement can lead to
      pronounced changes in the particles' electronic properties, indicating that the
      known importance of surface effects is further enhanced in nanoalloys.

PMID- 22456834
TI  - Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and
      environmental relevance.
AB  - Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of
      clothes, carpets and leather products, and as lubricants, pesticides, in paints
      and medicine. Recent developments in chemical analysis have revealed that
      fluorinated compounds have become ubiquitously spread and are regarded as a
      potential threats to the environment. Due to the carbon-fluorine bond, which has
      a very high bond strength, these chemicals are extremely persistent towards
      degradation and some PFCs have a potential for bioaccumulation in organisms. Of
      particular concern has been the developmental toxicity of PFOS and PFOA, which
      has been manifested in rodent studies as high mortality of prenatally exposed
      newborn rats and mice within 24 h after delivery. The nervous system appears to
      be one of the most sensitive targets of environmental contaminants. The serious
      developmental effects of PFCs have lead to the upcoming of studies that have
      investigated neurotoxic effects of these substances. In this review the major
      findings of the neurotoxicity of the main PFCs and their suggested mechanisms of
      action are presented. The neurotoxic effects are discussed in light of other
      toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The
      main findings are that PFCs may induce neurobehavioral effects, particularly in
      developmentally exposed animals. The effects are, however, subtle and
      inconclusive and are often induced at concentrations where other toxic effects
      also are expected. Mechanistic studies have shown that PFCs may affect the
      thyroid system, influence the calcium homeostasis, protein kinase C, synaptic
      plasticity and cellular differentiation. Compared to other environmental
      toxicants the human blood levels of PFCs are high and of particular concern is
      that susceptible groups may be exposed to a cocktail of substances that in
      combination reach harmful concentrations.

PMID- 22456836
TI  - Genotoxicity investigations on nanomaterials.
AB  - This review is based on the lecture presented at the April 2010 nanomaterials
      safety assessment Postsatellite to the 2009 EUROTOX Meeting and summarizes
      genotoxicity investigations on nanomaterials published in the open scientific
      literature (up to 2008). Special attention is paid to the relationship between
      particle size and positive versus negative outcome, as well as the dependence of
      the outcome on the test used. Salient conclusions and outstanding recommendations
      emerging from the information summarized in this review are as follows: recognize
      that nanomaterials are not all the same; therefore know and document what
      nanomaterial has been tested and in what form; take nanomaterials specific
      properties into account; in order to make your results comparable with those of
      others and on other nanomaterials: use or at least include in your studies
      standardized methods; use in vivo studies to put in vitro results into
      perspective; take uptake and distribution of the nanomaterial into account; and
      in order to become able to make extrapolations to risk for human: learn about the
      mechanism of nanomaterials genotoxic effects. Past experience with standard non
      nanosubstances already had shown that mechanisms of genotoxic effects can be
      complex and their elucidation can be demanding, while there often is an immediate
      need to assess the genotoxic hazard. Thus, a practical and pragmatic approach to
      genotoxicity investigations of novel nanomaterials is the use of a battery of
      standard genotoxicity testing methods covering a wide range of mechanisms.
      Application of these standard methods to nanomaterials demands, however,
      adaptations, and the interpretation of results from the genotoxicity testing of
      nanomaterials needs additional considerations exceeding those used for standard
      size materials.

PMID- 22456835
TI  - A novel type of silver nanoparticles and their advantages in toxicity testing in
      cell culture systems.
AB  - Silver nanoparticles (SNPs) are among the most commercialized nanoparticles
      worldwide. Often SNP are used because of their antibacterial properties. Besides
      that they possess unique optic and catalytic features, making them highly
      interesting for the creation of novel and advanced functional materials. Despite
      its widespread use only little data exist in terms of possible adverse effects of
      SNP on human health. Conventional synthesis routes usually yield products of
      varying quality and property. It thus may become puzzling to compare biological
      data from different studies due to the great variety in sizes, coatings or shapes
      of the particles applied. Here, we applied a novel synthesis approach to obtain
      SNP of well-defined colloidal and structural properties. Being stabilized by a
      covalently linked small peptide, these particles are nicely homogenous, with
      narrow size distribution, and form monodisperse suspensions in aqueous solutions.
      We applied these peptide-coated SNP in two different sizes of 20 or 40 nm
      (Ag20Pep and Ag40Pep) and analyzed responses of THP-1-derived human macrophages
      while being exposed against these particles. Gold nanoparticles of similar size
      and coating (Au20Pep) were used for comparison. The cytotoxicity of particles was
      assessed by WST-1 and LDH assays, and the uptake into the cells was confirmed via
      transmission electron microscopy. In summary, our data demonstrate that this
      novel type of SNP is well suited to serve as model system for nanoparticles to be
      tested in toxicological studies in vitro.

PMID- 22456837
TI  - Injectable hydrogels for bone and cartilage repair.
AB  - Injectable in situ crosslinkable gels are highly desirable clinically as they can
      be introduced into a body via a minimally invasive manner using endoscopic or
      percutaneous procedures. Several hydrophilic polymeric systems that respond to
      stimuli such as light, temperature, pH, ionic concentration as well as those that
      can undergo chemical reactions to form crosslinked matrices are currently under
      development. This paper discusses the applications of hydrogels as scaffolds to
      mimic the native extracellular matrix of bone and cartilage. A comprehensive
      description of various gelation methods used in hydrogel preparation and their
      application as injectable cell and protein delivery vehicle for bone and
      cartilage regeneration is also presented.

PMID- 22456847
TI  - Primary infrarenal aortic stenting with or without iliac stenting for isolated
      and aortoiliac stenoses: single-centre experience with long-term follow-up.
AB  - PURPOSE: The purpose of this study was to evaluate the technical success,
      complications, long-term clinical outcome, and patency after primary infrarenal
      aortic stenting for aortic and aortoiliac stenosis. Between January 1999 and
      January 2006, 22 consecutive patients underwent endovascular treatment because of
      infrarenal aortic stenosis with and without common iliac stenosis (10 men; mean
      age 64 +/- 14 years). Eleven (11 of 22) patients had an isolated aortic stenosis,
      whereas 11 of 22 had aortic stenosis that extended into the common iliac arteries
      (CIAs). Thirteen patients were Rutherford classification type 3, and 9 patients
      were type 4. Statistical analysis included paired Student t test and Kaplan-Meier
      life table analysis; p < 0.05 was considered significant. Technical and initial
      clinical success was achieved in all patients. There were three (14 %) procedure
      related complications, which included two access-point pseudoaneurysms and one
      non-flow-limiting left external iliac dissection. Patients were followed-up for a
      mean period of 88 months (range 60-132). Mean preprocedure ankle brachial
      pressure indexes (ABPI) were 0.60 +/- -0.15 (right) and 0.61 +/- -0.16 (left).
      After the procedure they were 0.86 +/- -0.07 (right) and 0.90 +/- -0.09 (left).
      The increase in ABPI was significant (p < 0.05), and this continued throughout
      follow-up. Four (18 %) patients had recurrence of symptoms during follow-up.
      These occurred at 36, 48, 48, and 50 months after the original procedure. All
      four patients were successfully treated with repeat angioplasty procedures. There
      was a significant difference in primary patency between isolated aortic stenosis
      (100 %) and aortoiliac stenosis (60 %) (p = 0.031). Cumulative follow-up was 1920
      months yielding a reintervention rate of 0.025/events/year. CONCLUSION: Primary
      stenting of infrarenal stenosis is safe and successful with a low reintervention
      rate. It should be considered as first-line treatment for patients with
      infrarenal aortic stenotic disease.

PMID- 22456851
TI  - Structural characterization of the lithium silicides Li15Si4, Li13Si4, and Li7Si3
      using solid state NMR.
AB  - Local environments and lithium ion dynamics in the binary lithium silicides
      Li(15)Si(4), Li(13)Si(4), and Li(7)Si(3) have been characterized by detailed
      variable temperature static and magic-angle spinning (MAS) NMR spectroscopic
      experiments. In the (6)Li MAS-NMR spectra, individual lithium sites are generally
      well-resolved at temperatures below 200 K, whereas at higher temperatures partial
      or complete site averaging is observed on the ms timescale. The NMR spectra also
      serve to monitor the phase transitions occurring in Li(7)Si(3) and Li(13)Si(4) at
      235 K and 146 K, respectively. The observed lithium isotropic shift ranges of up
      to approximately 50 ppm indicate a significant amount of electronic charge stored
      on the lithium species, consistent with the expectation of the extended Zintl
      Klemm-Busmann concept for the electronic structure of these materials. The (29)Si
      MAS-NMR spectra obtained on isotopically enriched samples, aided by double
      quantum spectroscopy, are well suited for differentiating between the individual
      types of silicon sites within the silicon frameworks, and in Li(13)Si(4) their
      identification aids in the assignment of individual lithium sites
      via(29)Si{(7)Li} cross-polarization/heteronuclear correlation NMR. Variable
      temperature static (7)Li NMR spectra reveal motional narrowing effects,
      illustrating high lithium ionic mobilities in all of these compounds. Differences
      in the mobilities of individual lithium sites can be resolved by temperature
      dependent (6)Li MAS-NMR as well as (6)Li{(7)Li} rotational echo double resonance
      (REDOR) spectroscopy. For the compound Li(15)Si(4) the lithium mobility appears
      to be strongly geometrically restricted, which may result in a significant
      impediment for the use of Li-Si anodes for high-performance batteries. A
      comparison of all the (6)Li and (7)Li NMR spectroscopic data obtained for the
      three different lithium silicides and of Li(12)Si(7) previously studied suggests
      that lithium ions in the vicinity of silicon clusters or dimers have generally
      higher mobilities than those interacting with monomeric silicon atoms.

PMID- 22456850
TI  - Evaluation of environmental magnetic pollution screening in soils of basaltic
      origin: results from Nashik Thermal Power Station, Maharashtra, India.
AB  - BACKGROUND, AIM, AND SCOPE: Soils of basaltic origin cause difficulties in
      environmental magnetic screening for heavy metal pollution due to their natural
      high background values. Magnetic parameters and heavy metal content of highly
      magnetic topsoils from the Deccan Trap basalts are investigated to assess their
      potential for use in environmental magnetic pollution screening. This work
      extends the fast and cost-effective magnetic pollution screening techniques into
      soils with high natural magnetic signals. MATERIALS AND METHODS: Fifty-five
      topsoil samples from N-S and W-E transects were collected and subdivided
      according to grain size using wet sieving technique. Magnetic susceptibility,
      soft isothermal remanent magnetization (Soft IRM), thermomagnetic analysis,
      scanning electron microscopy (SEM), and heavy metal analysis were performed on
      the samples. RESULTS: Magnetic analyses reveal a significant input of
      anthropogenic magnetic particulate matter within 6 km of the power plant and the
      adjacent ash pond. Results depend strongly on the stage of soil development and
      vary spatially. While results in the W, E, and S directions are easily
      interpretable, in the N direction, the contribution of the anthropogenic magnetic
      matter is difficult to assess due to high magnetic background values, less
      developed soils, and a more limited contribution from the fly ash sources.
      Prevailing winds towards directions with more enhanced values seem to have a
      certain effect on particulate matter accumulation in the topsoil. Thermomagnetic
      measurements show Verwey transition and Hopkinson peak, thus proving the presence
      of ferrimagnetic mineral phases close to the pollution source. A quantitative
      decrease of the anthropogenic ferrimagnetic mineral concentration with increased
      distance is evident in Soft IRM measurements. SEM investigations of
      quantitatively extracted magnetic particles confirm the fly ash distribution
      pattern obtained from the magnetic and heavy metal analyses. Evaluation of
      magnetic and chemical data in concert with the Pollution Load IndiceS (PLIS) of
      Pb, Zn, and Cu reveals a good relationship between magnetic susceptibility and
      the metal content. CONCLUSIONS: Integrated approaches in data acquisition of
      magnetic and chemical parameters enable the application of magnetic screening
      methods in highly magnetic soils. Combined data evaluation allows identification
      of sampling sites that are affected by human activity, through the deviation of
      the magnetic and chemical data from the general trend. It is shown that
      integrative analysis of magnetic parameters and a limited metal concentration
      dataset can enhance the quality of the output of environmental magnetic pollution
      screening significantly.

PMID- 22456852
TI  - Procalcitonin and C-reactive protein in pericardial fluid for postmortem
      diagnosis of sepsis.
AB  - The aim of this study was to investigate the presence and concentrations of
      procalcitonin and C-reactive protein in pericardial fluid and compare these
      levels to those found in the postmortem serum obtained from the femoral blood.
      Two groups were formed, a sepsis-related fatalities group and a control group.
      Postmortem native CT scans, autopsies, histology, neuropathology and toxicology
      as well as other postmortem biochemistry investigations were performed in all
      cases. Pericardial fluid procalcitonin levels were significantly different
      between the cases of sepsis-related fatalities and those of the control group.
      Postmortem serum procalcitonin levels below the detection limit were also
      reflected in undetectable pericardial fluid levels. Similarly, a large increase
      in postmortem serum procalcitonin levels was reflected in a large increase of
      procalcitonin pericardial fluid levels. Based on these findings, pericardial
      fluid could be an alternative to postmortem serum for the determination of
      procalcitonin levels in cases where postmortem serum is not available and
      measurements of procalcitonin are required to circumstantiate the pathogenesis of
      death.

PMID- 22456853
TI  - Membrane potential-dependent inhibition of the Na+,K+-ATPase by para
      nitrobenzyltriethylammonium bromide.
AB  - Membrane potential (V(M))-dependent inhibitors of the Na(+),K(+)-ATPase are a new
      class of compounds that may have inherent advantages over currently available
      drugs targeting this enzyme. However, two questions remain unanswered regarding
      these inhibitors: (1) what is the mechanism of V(M)-dependent Na(+),K(+)-ATPase
      inhibition, and (2) is their binding affinity high enough to consider them as
      possible lead compounds? To address these questions, we investigated how a
      recently synthesized V(M)-dependent Na(+),K(+)-ATPase inhibitor, para
      nitrobenzyltriethylamine (pNBTEA), binds to the enzyme by measuring the
      extracellular pNBTEA concentration and V(M) dependence of ouabain-sensitive
      transient charge movements in whole-cell patch-clamped rat cardiac ventricular
      myocytes. By analyzing the kinetics of charge movements and the steady-state
      distribution of charge, we show that the V(M)-dependent properties of pNBTEA
      binding differ from those for extracellular Na(+) and K(+) binding, even though
      inhibitor binding is competitive with extracellular K(+). The data were also fit
      to specific models for pNBTEA binding to show that pNBTEA binding is a rate
      limiting V(M)-dependent reaction that, in light of homology models for the
      Na(+),K(+)-ATPase, we interpret as a transfer reaction of pNBTEA from a
      peripheral binding site in the enzyme to a site near the known K(+) coordination
      sites buried within the transmembrane helices of the enzyme. These models also
      suggest that binding occurs with an apparent affinity of 7 MUM. This apparent
      binding affinity suggests that high-affinity V(M)-dependent Na(+),K(+)-ATPase
      inhibitors should be feasible to design and test as specific enzyme inhibitors.

PMID- 22456854
TI  - Children's gender and parents' color preferences.
AB  - Gender differences in color preferences have been found in adults and children,
      but they remain unexplained. This study asks whether the gendered social
      environment in adulthood affects parents' color preferences. The analysis used
      the gender of children to represent one aspect of the gendered social
      environment. Because having male versus female children in the U.S. is generally
      randomly distributed, it provides something of a natural experiment, offering
      evidence about the social construction of gender in adulthood. The participants
      were 749 adults with children who responded to an online survey invitation,
      asking "What's your favorite color?" Men were more likely to prefer blue, while
      women were more likely to prefer red, purple, and pink, consistent with long
      standing U.S. patterns. The effect of having only sons was to widen the existing
      gender differences between men and women, increasing the odds that men prefer
      blue while reducing the odds that women do; and a marginally significant effect
      showed women having higher odds of preferring pink when they have sons only. The
      results suggest that, in addition to any genetic, biological or child
      socialization effects shaping adults' tendency to segregate their color
      preferences by gender, the gender context of adulthood matters as well.

PMID- 22456855
TI  - Cosmetic clitoridectomy in a 33-year-old woman: reply to Friedman (2011) and
      Levine (2011).

PMID- 22456856
TI  - Effectiveness of anterior cruciate ligament injury prevention training programs.
AB  - BACKGROUND: The objective of this study was to systematically review the
      literature on anterior cruciate ligament (ACL) injury prevention programs and to
      perform a meta-analysis to address three questions: First, what is the
      effectiveness of ACL injury prevention programs? Second, is there evidence for a
      "best" program? Third, what is the quality of the current literature on ACL
      injury prevention? METHODS: We conducted a systematic review with use of the
      online PubMed, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied
      Health), and Cochrane Central Register of Controlled Trials databases. Search
      terms were anterior cruciate ligament, knee, injury, prevention, and control.
      Data on study design and clinical outcomes were extracted independently in
      triplicate. After assessment of between-study heterogeneity, DerSimonian-Laird
      random-effect models were used to calculate pooled risk ratios and risk
      differences. The risk difference was used to estimate the number needed to treat
      (the number of individuals who would need to be treated to avoid one ACL tear).
      RESULTS: The pooled risk ratio was 0.38 (95% confidence interval [CI], 0.20 to
      0.72), reflecting a significant reduction in the risk of ACL rupture in the
      prevention group (p = 0.003). The number needed to treat ranged from five to 187
      in the individual studies. Stratified by sex, the pooled risk ratio was 0.48 (95%
      CI, 0.26 to 0.89) for female athletes and 0.15 (95% CI, 0.08 to 0.28) for male
      athletes. CONCLUSIONS: Our study indicated strong evidence in support of a
      significant effect of ACL injury prevention programs. Our pooled estimates
      suggest a substantial beneficial effect of ACL injury prevention programs, with a
      risk reduction of 52% in the female athletes and 85% in the male athletes.

PMID- 22456857
TI  - An ounce of prevention beats a pound of reconstruction: commentary on an article
      by Patrick Sadoghi, MD, et al.: "Effectiveness of anterior cruciate ligament
      injury prevention training programs".

PMID- 22456858
TI  - Stability and free energy calculation of LNA modified quadruplex: a molecular
      dynamics study.
AB  - Telomeric ends of chromosomes, which comprise noncoding repeat sequences of
      guanine-rich DNA, which are the fundamental in protecting the cell from
      recombination and degradation. Telomeric DNA sequences can form four stranded
      quadruplex structures, which are involved in the structure of telomere ends. The
      formation and stabilization of telomeric quadruplexes has been shown to inhibit
      the activity of telomerase, thus establishing telomeric DNA quadrulex as an
      attractive target for cancer therapeutic intervention. Molecular dynamic
      simulation offers the prospects of detailed description of the dynamical
      structure with ion and water at molecular level. In this work we have taken a
      oligomeric part of human telomeric DNA, d(TAGGGT) to form different monomeric
      quadruplex structures d(TAGGGT)4. Here we report the relative stabilities of
      these structures under K+ ion conditions and binding interaction between the
      strands, as determined by molecular dynamic simulations followed by energy
      calculation. We have taken locked nucleic acid (LNA) in this study. The free
      energy molecular mechanics Poission Boltzman surface area calculations are
      performed for the determination of most stable complex structure between all
      modified structures. We calculated binding free energy for the combination of
      different strands as the ligand and receptor for all structures. The energetic
      study shows that, a mixed hybrid type quadruplex conformation in which two
      parallel strands are bind with other two antiparallel strands, are more stable
      than other conformations. The possible mechanism for the inhibition of the
      cancerous growth has been discussed. Such studies may be helpful for the rational
      drug designing.

PMID- 22456859
TI  - Computer-aided design of novel antibacterial 3-hydroxypyridine-4-ones:
      application of QSAR methods based on the MOLMAP approach.
AB  - 3-Hydroxypyridine-4-one derivatives have shown good inhibitory activity against
      bacterial strains. In this work we report the application of MOLMAP descriptors
      based on empirical physicochemical properties with genetic algorithm partial
      least squares (GA-PLS) and counter propagation artificial neural networks (CP
      ANN) methods to propose some novel 3-hydroxypyridine-4-one derivatives with
      improved antibacterial activity against Staphylococcus aureus. A large collection
      of 302 novel derivatives of this chemical scaffold was selected for this purpose.
      The activity classes of these compounds were determined using the two
      quantitative structure activity relationships models. To evaluate the
      predictability and accuracy of the obtained models, nineteen compounds belonging
      to all three activity classes were prepared and the activity of them was
      determined against S. aureus. Comparing the experimental results and the
      predicted activity classes revealed the accuracy of the obtained models.
      Seventeen of the nineteen synthesized molecules were correctly predicted by GA
      PLS model according to the antimicrobial evaluation method. Molecules 5f and 5h
      proved to be moderately active and active experimentally, but were predicted as
      inactive and moderately active compounds, respectively by this model. The CP-ANN
      based prediction was correct for sixteen out of the nineteen synthesized
      molecules. 5a, 5h and 5q were moderately active and active based on the
      antimicrobial assays, but they were introduced as members of inactive, moderately
      active and inactive classes of compounds, respectively according to CP-ANN model.

PMID- 22456860
TI  - Viral infections of the lower respiratory tract.
AB  - Lower respiratory tract infections (LRTIs) are a global burden to public health
      and are frequently caused by respiratory viruses. Advances in molecular
      diagnostic techniques have allowed the identification of previously undetected
      viral pathogens and have improved our understanding of respiratory virus
      infections. Here we review the epidemiological and clinical characteristics of
      recently identified viruses including human metapneumovirus, human coronaviruses
      NL63 and HKU1, human rhinovirus C, bocavirus, WU and KI polyomaviruses, and
      parechovirus. The roles of these viruses in LRTIs in children and adults are
      discussed.

PMID- 22456861
TI  - Determination of gas-phase ozonolysis rate coefficients of a number of
      sesquiterpenes at elevated temperatures using the relative rate method.
AB  - The rates of ozonolysis of four sesquiterpenes, beta-caryophyllene, alpha
      humulene, isolongifolene and alpha-cedrene, are determined in the gas phase at an
      elevated temperature of 366 +/- 3 K and a pressure of ~780 Torr using the EXTreme
      RAnge chamber (EXTRA). The experimentally obtained rate coefficients agree with
      extrapolated room temperature rate coefficients for isolongifolene and alpha
      cedrene but not for beta-caryophyllene and alpha-humulene, which were found to be
      three orders of magnitude slower than this in the literature. These new
      measurements support the hypothesis that operating under ambient conditions,
      kinetic measurements of condensable species can be influenced adversely by
      heterogeneous processes and should therefore be treated with caution.

PMID- 22456862
TI  - The effects of energy drink in combination with alcohol on performance and
      subjective awareness.
AB  - RATIONALE: This study investigated the coadministration of an energy drink with
      alcohol to study the effects on subjective intoxication and objective
      performance. OBJECTIVES: This study aims to evaluate the objective and subjective
      effects of alcohol versus placebo at two alcohol doses, alone and in combination
      with an energy drink, in a balanced order, placebo-controlled, double-blind
      design. METHODS: Two groups of ten healthy volunteers, mean (SD) age of 24 (6.5),
      participated in the study. One group consumed energy drink containing 80 mg of
      caffeine and the other consumed a placebo drink, with both receiving two alcohol
      doses (0.046 and 0.087% breathalyser alcohol concentration). Tests included
      breath alcohol assessment, objective measures of performance (reaction time, word
      memory and Stroop task) and subjective visual analogue mood scales. RESULTS:
      Participants showed significantly impaired reaction time and memory after alcohol
      compared to the no alcohol condition and had poorer memory after the higher
      alcohol dose. Stroop performance was improved with the energy drink plus alcohol
      combination compared to the placebo drink plus alcohol combination. Participants
      felt significant subjective dose-related impairment after alcohol compared to no
      alcohol. Neither breath alcohol concentration nor the subjective measures showed
      a significant difference between the energy drink and the placebo energy drink
      when combined with alcohol. CONCLUSIONS: Subjective effects reflected awareness
      of alcohol intoxication and sensitivity to increasing alcohol dose. There were no
      overall significant group differences for subjective measures between energy
      drink and placebo groups in the presence of alcohol and no evidence that the
      energy drink masked the subjective effects of alcohol at either dose.

PMID- 22456863
TI  - Vascular injury in cancer survivors.
AB  - With an increase in the number of patients surviving many years following
      successful cancer treatment, has come an improved understanding of the long-term
      effects of cancer therapy and its implications on future health. Premature
      cardiovascular disease is a significant cause of early morbidity and the leading
      non-cancer cause of death in this population. Chemotherapeutic agents and
      radiation therapy are known to be cardiotoxic. However, numerous vascular-related
      toxicities have also been observed among cancer survivors, such as myocardial
      ischemia, transient ischemic attacks, and stroke, suggesting a degree of chronic
      endothelial injury and dysfunction leading to premature atherosclerotic disease.
      Vascular health in cancer survivors may be further compromised by metabolic
      abnormalities such as obesity, insulin resistance, and dyslipidemias which have
      also been reported following cancer therapy. Furthermore, some survivors
      experience gonadal dysfunction and loss of potentially protective sex steroids or
      undergo hormonal therapies that induce additional metabolic abnormalities. The
      effects of cancer therapies upon the endothelial monolayer have not been fully
      explored. An understanding of potential injury to and dysfunction of the
      circulatory system among cancer survivors is essential for identifying preventive
      strategies and therapeutic targets.

PMID- 22456864
TI  - Assessment of patient-led or physician-driven continuous glucose monitoring in
      patients with poorly controlled type 1 diabetes using basal-bolus insulin
      regimens: a 1-year multicenter study.
AB  - OBJECTIVE: The benefits of real-time continuous glucose monitoring (CGM) have
      been demonstrated in patients with type 1 diabetes. Our aim was to compare the
      effect of two modes of use of CGM, patient led or physician driven, for 1 year in
      subjects with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS:
      Patients with type 1 diabetes aged 8-60 years with HbA(1c) >= 8% were randomly
      assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1
      year for two modes of CGM (group 1: patient led; group 2: physician driven)
      versus conventional self-monitoring of blood glucose (group 3: control). RESULTS:
      A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197
      were randomized, with 178 patients completing the study (age: 36 +/- 14 years;
      HbA(1c): 8.9 +/- 0.9%). HbA(1c) improved similarly in both CGM groups and was
      reduced compared with the control group (group 1 vs. group 3: -0.52%, P = 0.0006;
      group 2 vs. group 3: -0.47%, P = 0.0008; groups 1 + 2 vs. group 3: -0.50%, P <
      0.0001). The incidence of hypoglycemia was similar in the three groups. Patient
      SF-36 questionnaire physical health score improved in both experimental CGM
      groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1
      (median [Q1-Q3] consumption: group 1: 3.42/month [2.20-3.91] vs. group 2:
      2.25/month [1.27-2.99], P = 0.001). CONCLUSIONS: Both patient-led and physician
      driven CGM provide similar long-term improvement in glucose control in patients
      with poorly controlled type 1 diabetes, but the physician-driven CGM mode used
      fewer sensors.

PMID- 22456865
TI  - Longitudinal trajectories of HbA1c and fasting plasma glucose levels during the
      development of type 2 diabetes: the Toranomon Hospital Health Management Center
      Study 7 (TOPICS 7).
AB  - OBJECTIVE: To describe the trajectory of HbA(1c) and glucose concentrations
      before the diagnosis of diabetes. RESEARCH DESIGN AND METHODS: The study
      comprised 1,722 nondiabetic Japanese individuals aged 26-80 years. Fasting plasma
      glucose (FPG) and HbA(1c) were measured annually for a mean of 9.5 (SD 1.8)
      years. RESULTS: Diabetes occurred in 193 individuals (FPG >= 7.0 mmol/L, self
      reported clinician-diagnosed diabetes, or HbA(1c) >= 6.5%). Mean HbA(1c) values
      were >5.6% each year before diagnosis in diabetes cases. Mean HbA(1c) (5.69% [95%
      CI 5.50-5.88]) was higher in the 21 individuals who developed diabetes 10 years
      after the baseline examination than in nondiabetic individuals after 10 years
      (5.27% [5.25-5.28]). From 3 years to 1 year prediagnosis, HbA(1c) increased 0.09%
      (SE 0.01)/year, reaching 5.90% (5.84-5.96) 1 year prediagnosis. In the entire
      group, marked increases in HbA(1c) of 0.3% (SE 0.05%)/year and FPG of 0.63 (0.07)
      mmol/L/year predicted diabetes. CONCLUSIONS: HbA(1c) trajectory increased sharply
      after gradual long-term increases in diabetic individuals.

PMID- 22456866
TI  - The relationship between financial incentives and quality of diabetes care in
      Ontario, Canada.
AB  - OBJECTIVE: We assessed the impact of a diabetes incentive code introduced for
      primary care physicians in Ontario, Canada, in 2002 on quality of diabetes care
      at the population and patient level. RESEARCH DESIGN AND METHODS: We analyzed
      administrative data for 757,928 Ontarians with diabetes to examine the use of the
      code and receipt of three evidence-based monitoring tests from 2006 to 2008. We
      assessed testing rates over time and before and after billing of the incentive
      code. RESULTS: One-quarter of Ontarians with diabetes had an incentive code
      billed by their physician. The proportion receiving the optimal number of all
      three monitoring tests (HbA(1c), cholesterol, and eye tests) rose gradually from
      16% in 2000 to 27% in 2008. Individuals who were younger, lived in rural areas,
      were not enrolled in a primary care model, or had a mental illness were less
      likely to receive all three recommended tests. Patients with higher numbers of
      incentive code billings in 2006-2008 were more likely to receive recommended
      testing but also were more likely to have received the highest level of
      recommended testing prior to introduction of the incentive code. Following the
      same patients over time, improvement in recommended testing was no greater after
      billing of the first incentive code than before. CONCLUSIONS: The diabetes
      incentive code led to minimal improvement in quality of diabetes care at the
      population and patient level. Our findings suggest that physicians who provide
      the highest quality care prior to incentives may be those most likely to claim
      incentive payments.

PMID- 22456867
TI  - Statin use as a moderator of metformin effect on risk for prostate cancer among
      type 2 diabetic patients.
AB  - OBJECTIVE: Metformin and statins have shown promise for cancer prevention. This
      study assessed whether the effect of metformin on prostate cancer (PCa) incidence
      varied by statin use among type 2 diabetic patients. RESEARCH DESIGN AND METHODS:
      The study cohort consisted of 5,042 type 2 diabetic male patients seen in the
      Veteran Administration Health Care System who were without prior cancer and were
      prescribed with metformin or sulfonylurea as the exclusive hypoglycemic
      medication between fiscal years 1999 and 2005. Cox proportional hazards analyses
      were conducted to assess the differential hazard ratio (HR) of PCa due to
      metformin by statin use versus sulfonylurea use, where propensity scores of
      metformin and statin use were adjusted to account for imbalances in baseline
      covariates across medication groups. RESULTS: Mean follow-up was 5 years, and
      7.5% had a PCa diagnosis. Statin use modified the effect of metformin on PCa
      incidence (P < 0.0001). Metformin was associated with a significantly reduced PCa
      incidence among patients on statins (HR 0.69 [95% CI 0.50-0.92]; 17 cases/533
      metformin users vs. 135 cases/2,404 sulfonylureas users) and an increased PCa
      incidence among patients not on statins (HR 2.15 [1.83-2.52]; 22 cases/175
      metformin users vs. 186 cases/1,930 sulfonylureas users). The HR of PCa incidence
      for those taking metformin and statins versus those taking neither medication was
      0.32 (0.25-0.42). CONCLUSIONS: Among men with type 2 diabetes, PCa incidence
      among metformin users varied by their statin use. The potential beneficial
      influence on PCa by combination use of metformin and statin may be due to
      synergistic effects.

PMID- 22456869
TI  - Degradable, click poly(vinyl alcohol) hydrogels: characterization of degradation
      and cellular compatibility.
AB  - The aim of this research was to understand the influence of functional group
      density on degradation and cell survival within injectable poly(vinyl alcohol)
      (PVA) hydrogels crosslinked through hydrazone bonds. For this purpose, PVA was
      modified with aldehyde and hydrazide functional groups. The click reaction
      between these two macromers, performed under physiologic conditions, led to
      hydrogel formation in less than 3 min. The influence of the crosslinking density
      on the gelation time, volumetric swelling ratio and mass loss of the hydrogels
      was investigated. These systems were slowly degradable as they maintained their
      gel-like state for more than 120 days. However, these networks also exhibited
      unusual degradation behaviour that could be the result of a breaking-forming bond
      phenomenon, attributable to the reversible nature of the hydrazone bond. This
      study also demonstrated that these networks maintained their mechanical strength
      while degrading, and cell encapsulation revealed the cytocompatibility of these
      systems.

PMID- 22456871
TI  - A novel case of concurrent renal tumors: chromophobe renal cell carcinoma and
      carcinoid tumor of the kidney with brief review of renal neuroendocrine tumors.
AB  - Renal cell carcinoma of chromophobe type is a malignant neoplasm with
      characteristic large cells that exhibit prominent cell membranes. Primary renal
      carcinoid tumors are rare tumors with the histological appearance similar to well
      differentiated neuroendocrine tumors at other sites. Chromophobe renal cell
      carcinoma with neuroendocrine differentiation is exceedingly rare. The authors
      describe a case of a chromophobe renal cell carcinoma and carcinoid tumor of the
      kidney presenting as distinct masses in the same kidney in a 34-year-old male.
      The histologic and immunohistochemical features of both the tumors were
      characteristic with no overlapping features. The carcinoid tumor presented at a
      higher stage with nodal metastasis. To the best of the authors' knowledge, this
      is the first case of 2 morphologically distinct tumors, one chromophobe renal
      cell carcinoma and the other primary carcinoid tumor in the same kidney.

PMID- 22456868
TI  - Estimating hepatic glucokinase activity using a simple model of lactate kinetics.
AB  - OBJECTIVE: Glucokinase (GCK) acts as a component of the "glucose sensor" in
      pancreatic beta-cells and possibly in other tissues, including the brain.
      However, >99% of GCK in the body is located in the liver, where it serves as a
      "gatekeeper", determining the rate of hepatic glucose phosphorylation. Mutations
      in GCK are a cause of maturity-onset diabetes of the young (MODY), and GCKR, the
      regulator of GCK in the liver, is a diabetes susceptibility locus. In addition,
      several GCK activators are being studied as potential regulators of blood
      glucose. The ability to estimate liver GCK activity in vivo for genetic and
      pharmacologic studies may provide important physiologic insights into the
      regulation of hepatic glucose metabolism. RESEARCH DESIGN AND METHODS: Here we
      introduce a simple, linear, two-compartment kinetic model that exploits lactate
      and glucose kinetics observed during the frequently sampled intravenous glucose
      tolerance test (FSIGT) to estimate liver GCK activity (K(GK)), glycolysis
      (K(12)), and whole body fractional lactate clearance (K(01)). RESULTS To test our
      working model of lactate, we used cross-sectional FSIGT data on 142 nondiabetic
      individuals chosen at random from the Finland-United States Investigation of
      NIDDM Genetics study cohort. Parameters K(GK), K(12), and K(01) were precisely
      estimated. Median model parameter estimates were consistent with previously
      published values. CONCLUSIONS: This novel model of lactate kinetics extends the
      utility of the FSIGT protocol beyond whole-body glucose homeostasis by providing
      estimates for indices pertaining to hepatic glucose metabolism, including hepatic
      GCK activity and glycolysis rate.

PMID- 22456872
TI  - Multilocular cystic renal cell carcinoma in lower pole moiety of a duplex kidney.
AB  - Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon low-grade renal
      cell carcinoma with unique morphologic features. The 2004 World Health
      Organization classification of kidney tumors categorized MCRCC as a separate
      entity. The authors report the case of a 48-year-old man whose MCRCC originated
      from the lower portion of the duplex kidney (DK). Because the oncological outcome
      of MCRCC is favorable, regardless of tumor size and stage, patients with MCRCC
      might benefit from nephron-sparing surgery. It is important to distinguish larger
      MCRCCs from other renal cell carcinomas, especially when comorbid with DK,
      because the characteristic anatomy of DK warrants the nephron-sparing surgery. To
      the authors' knowledge, MCRCC in DK has not been reported previously in the
      English literature.

PMID- 22456873
TI  - Do adventitial mast cells contribute to the pathogenesis of ascending thoracic
      aorta aneurysm?
AB  - The precise pathogenesis of the ascending aortic aneurysm (AscAA) remains to be
      determined. Mast cells in the adventitia of human AscAA lesions may play a role
      in this pathogenesis. Adventitial mast cell density per 10 high-power fields
      (0.25 mm(2)) was assessed in multiple biopsy samples, from aneurysmal aortic
      sections (n = 41) and control (nondilated) aortic specimens (n = 50), stained by
      orcein-Giemsa method, an inexpensive (<$1) method. In a multivariable adjusted
      logistic regression model, using AscAA as the dependent variable, mast cell
      density was found to be an independent predictor of AscAA occurrence (odds ratio
      = 2.21; 95% confidence interval = 1.58-3.08; P < .001). Receiver operating
      characteristic curve analysis showed that the proposed cutoff value of >= 3 mast
      cells per 10 high-power fields was very sensitive to detect AscAA occurrence,
      yielding a sensitivity of 90% with a specificity of 80%. In conclusion, a
      significant increase in the number of mast cells in the adventitia of human
      ascending aortic lesions proposes a role for these cells in the pathogenesis of
      AscAA.

PMID- 22456874
TI  - Probing adenylation: using a fluorescently labelled ATP probe to directly label
      and immunoprecipitate VopS substrates.
AB  - The bacterial effector VopS from Vibrio parahaemolyticus modifies host Rho
      GTPases to prevent downstream signalling, which leads to cell rounding and
      eventually apoptosis. While previous studies have used [alpha-(32)P] ATP for
      studying this enzyme, we sought to develop a non-radioactive chemical probe of
      VopS function. To guide these studies, the kinetic parameters were determined for
      a variety of nucleotides and the results indicated that the C6 position of
      adenosine was amenable to modification. Since Fl-ATP is a commercially available
      ATP analogue that is fluorescently tagged at the C6 position, we tested it as a
      VopS substrate, and the results show that VopS uses Fl-ATP to label Cdc42 in
      vitro and in MCF7 whole cell extracts. The utility of this probe was further
      demonstrated by immunoprecipitating Fl-ATP labeled Cdc42 as well as several novel
      substrate proteins. The proteins, which were identified by LC-MS/MS, include the
      small GTPases Rac1 and Cdc42 as well as several proteins that are potential VopS
      substrates and may be important for V. parahaemolyticus pathology. In total,
      these studies identify Fl-ATP as a valuable chemical probe of protein AMPylation.

PMID- 22456876
TI  - Optimal shape and motion of undulatory swimming organisms.
AB  - Undulatory swimming animals exhibit diverse ranges of body shapes and motion
      patterns and are often considered as having superior locomotory performance. The
      extent to which morphological traits of swimming animals have evolved owing to
      primarily locomotion considerations is, however, not clear. To shed some light on
      that question, we present here the optimal shape and motion of undulatory
      swimming organisms obtained by optimizing locomotive performance measures within
      the framework of a combined hydrodynamical, structural and novel muscular model.
      We develop a muscular model for periodic muscle contraction which provides
      relevant kinematic and energetic quantities required to describe swimming. Using
      an evolutionary algorithm, we performed a multi-objective optimization for
      achieving maximum sustained swimming speed U and minimum cost of transport (COT)-
      two conflicting locomotive performance measures that have been conjectured as
      likely to increase fitness for survival. Starting from an initial population of
      random characteristics, our results show that, for a range of size scales, fish
      like body shapes and motion indeed emerge when U and COT are optimized. Inherent
      boundary-layer-dependent allometric scaling between body mass and kinematic and
      energetic quantities of the optimal populations is observed. The trade-off
      between U and COT affects the geometry, kinematics and energetics of swimming
      organisms. Our results are corroborated by empirical data from swimming animals
      over nine orders of magnitude in size, supporting the notion that optimizing U
      and COT could be the driving force of evolution in many species.

PMID- 22456877
TI  - Relationship between propagule pressure and colonization pressure in invasion
      ecology: a test with ships' ballast.
AB  - Increasing empirical evidence indicates the number of released individuals (i.e.
      propagule pressure) and number of released species (i.e. colonization pressure)
      are key determinants of the number of species that successfully invade new
      habitats. In view of these relationships, and the possibility that ships
      transport whole communities of organisms, we collected 333 ballast water and
      sediment samples to investigate the relationship between propagule and
      colonization pressure for a variety of diverse taxonomic groups (diatoms,
      dinoflagellates and invertebrates). We also reviewed the scientific literature to
      compare the number of species transported by ships to those reported in nature.
      Here, we show that even though ships transport nearly entire local communities, a
      strong relationship between propagule and colonization pressure exists only for
      dinoflagellates. Our study provides evidence that colonization pressure of
      invertebrates and diatoms may fluctuate widely irrespective of propagule
      pressure. We suggest that the lack of correspondence is explained by reduced
      uptake of invertebrates into the transport vector and the sensitivity of
      invertebrates and diatoms to selective pressures during transportation. Selection
      during transportation is initially evident through decreases in propagule
      pressure, followed by decreased colonization pressure in the most sensitive taxa.

PMID- 22456878
TI  - Disentangling effects of uncertainties on population projections: climate change
      impact on an epixylic bryophyte.
AB  - Assessment of future ecosystem risks should account for the relevant uncertainty
      sources. This means accounting for the joint effects of climate variables and
      using modelling techniques that allow proper treatment of uncertainties. We
      investigate the influence of three of the IPCC's scenarios of greenhouse gas
      emissions (special report on emission scenarios (SRES)) on projections of the
      future abundance of a bryophyte model species. We also compare the relative
      importance of uncertainty sources on the population projections. The whole chain
      global climate model (GCM)-regional climate model-population dynamics model is
      addressed. The uncertainty depends on both natural- and model-related sources, in
      particular on GCM uncertainty. Ignoring the uncertainties gives an unwarranted
      impression of confidence in the results. The most likely population development
      of the bryophyte Buxbaumia viridis towards the end of this century is negative:
      even with a low-emission scenario, there is more than a 65 per cent risk for the
      population to be halved. The conclusion of a population decline is valid for all
      SRES scenarios investigated. Uncertainties are no longer an obstacle, but a
      mandatory aspect to include in the viability analysis of populations.

PMID- 22456879
TI  - Species richness matters for the quality of ecosystem services: a test using seed
      dispersal by frugivorous birds.
AB  - The positive link between biodiversity and ecosystem functioning is a current
      paradigm in ecological science. However, little is known of how different
      attributes of species assemblages condition the quality of many services in real
      ecosystems affected by human impact. We explore the links between the attributes
      of a frugivore assemblage and the quantitative and qualitative components of its
      derived ecosystem service, seed dispersal, along a landscape-scale gradient of
      anthropogenic forest loss. Both the number and the richness of seeds being
      dispersed were positively related to frugivore abundance and richness. Seed
      dispersal quality, determined by the fine-scale spatial patterns of seed
      deposition, mostly depended on frugivore richness. In fact, richness was the only
      attribute of the frugivore assemblage affecting the probability of seed dispersal
      into deforested areas of the landscape. The positive relationships between
      frugivore richness per se (i.e. independent of frugivore abundance and
      composition) and all components of seed dispersal suggest the existence of
      functional complementarity and/or facilitation between frugivores. These links
      also point to the whole assemblage of frugivores as a conservation target, if we
      aim to preserve a complete seed dispersal service and, hence, the potential for
      vegetation regeneration and recovery, in human-impacted landscapes.

PMID- 22456880
TI  - Insertions and deletions trigger adaptive walks in Drosophila proteins.
AB  - Maps that relate all possible genotypes or phenotypes to fitness--fitness
      landscapes--are central to the evolution of life, but remain poorly known. An
      insertion or a deletion (indel) of one or several amino acids constitutes a
      substantial leap of a protein within the space of amino acid sequences, and it is
      unlikely that after such a leap the new sequence corresponds precisely to a
      fitness peak. Thus, one can expect an indel in the protein-coding sequence that
      gets fixed in a population to be followed by some number of adaptive amino acid
      substitutions, which move the new sequence towards a nearby fitness peak. Here,
      we study substitutions that occur after a frame-preserving indel in evolving
      proteins of Drosophila. An insertion triggers 1.03 +/- 0.75 amino acid
      substitutions within the protein region centred at the site of insertion, and a
      deletion triggers 4.77 +/- 1.03 substitutions within such a region. The
      difference between these values is probably owing to a higher fraction of
      effectively neutral insertions. Almost all of the triggered amino acid
      substitutions can be attributed to positive selection, and most of them occur
      relatively soon after the triggering indel and take place upstream of its site. A
      high fraction of substitutions that follow an indel occur at previously conserved
      sites, suggesting that an indel substantially changes selection that shapes the
      protein region around it. Thus, an indel is often followed by an adaptive walk of
      length that is in agreement with the theory of molecular adaptation.

PMID- 22456881
TI  - Does famine influence sex ratio at birth? Evidence from the 1959-1961 Great Leap
      Forward Famine in China.
AB  - The current study examined the long-term trend in sex ratio at birth between 1929
      and 1982 using retrospective birth histories of 310 101 Chinese women collected
      in a large, nationally representative sample survey in 1982. The study identified
      an abrupt decline in sex ratio at birth between April 1960, over a year after the
      Great Leap Forward Famine began, and October 1963, approximately 2 years after
      the famine ended, followed by a compensatory rise between October 1963 and July
      1965. These findings support the adaptive sex ratio adjustment hypothesis that
      mothers in good condition are more likely to give birth to sons, whereas mothers
      in poor condition are more likely to give birth to daughters. In addition, these
      findings help explain the lack of consistent evidence reported by earlier studies
      based on the 1944-1945 Dutch Hunger Winter or the 1942 Leningrad Siege.

PMID- 22456882
TI  - Is visual processing in the dorsal stream accessible to consciousness?
AB  - There are two highly interconnected clusters of visually responsive areas in the
      primate cortex. These two clusters have relatively few interconnections with each
      other, though those interconnections are undoubtedly important. One of the two
      main clusters (the dorsal stream) links the primary visual cortex (V1) to
      superior regions of the occipito-parietal cortex, while the other (the ventral
      stream) links V1 to inferior regions of the occipito-temporal cortex. According
      to our current understanding of the functional anatomy of these two systems, the
      dorsal stream's principal role is to provide real-time 'bottom-up' visual
      guidance of our movements online. In contrast, the ventral stream, in conjunction
      with top-down information from visual and semantic memory, provides perceptual
      representations that can serve recognition, visual thought, planning and memory
      offline. In recent years, this interpretation, initially based chiefly on studies
      of non-human primates and human neurological patients, has been well supported by
      functional MRI studies in humans. This perspective presents empirical evidence
      for the contention that the dorsal stream governs the visual control of movement
      without the intervention of visual awareness.

PMID- 22456883
TI  - Coprolites as a source of information on the genome and diet of the cave hyena.
AB  - We performed high-throughput sequencing of DNA from fossilized faeces to evaluate
      this material as a source of information on the genome and diet of Pleistocene
      carnivores. We analysed coprolites derived from the extinct cave hyena (Crocuta
      crocuta spelaea), and sequenced 90 million DNA fragments from two specimens. The
      DNA reads enabled a reconstruction of the cave hyena mitochondrial genome with up
      to a 158-fold coverage. This genome, and those sequenced from extant spotted
      (Crocuta crocuta) and striped (Hyaena hyaena) hyena specimens, allows for the
      establishment of a robust phylogeny that supports a close relationship between
      the cave and the spotted hyena. We also demonstrate that high-throughput
      sequencing yields data for cave hyena multi-copy and single-copy nuclear genes,
      and that about 50 per cent of the coprolite DNA can be ascribed to this species.
      Analysing the data for additional species to indicate the cave hyena diet, we
      retrieved abundant sequences for the red deer (Cervus elaphus), and characterized
      its mitochondrial genome with up to a 3.8-fold coverage. In conclusion, we have
      demonstrated the presence of abundant ancient DNA in the coprolites surveyed.
      Shotgun sequencing of this material yielded a wealth of DNA sequences for a
      Pleistocene carnivore and allowed unbiased identification of diet.

PMID- 22456884
TI  - Dental functional traits of mammals resolve productivity in terrestrial
      ecosystems past and present.
AB  - We have recently shown that rainfall, one of the main climatic determinants of
      terrestrial net primary productivity (NPP), can be robustly estimated from mean
      molar tooth crown height (hypsodonty) of mammalian herbivores. Here, we show that
      another functional trait of herbivore molar surfaces, longitudinal loph count,
      can be similarly used to extract reasonable estimates of rainfall but also of
      temperature, the other main climatic determinant of terrestrial NPP. Together,
      molar height and the number of longitudinal lophs explain 73 per cent of the
      global variation in terrestrial NPP today and resolve the main terrestrial biomes
      in bivariate space. We explain the functional interpretation of the relationships
      between dental function and climate variables in terms of long- and short-term
      demands. We also show how the spatially and temporally dense fossil record of
      terrestrial mammals can be used to investigate the relationship between
      biodiversity and productivity under changing climates in geological time. The
      placement of the fossil chronofaunas in biome space suggests that they most
      probably represent multiple palaeobiomes, at least some of which do not
      correspond directly to any biomes of today's world.

PMID- 22456885
TI  - Variation in founder groups promotes establishment success in the wild.
AB  - Environmental changes currently pose severe threats to biodiversity, and
      reintroductions and translocations are increasingly used to protect declining
      populations and species from extinction. Theory predicts that establishment
      success should be higher for more variable groups of dissimilar individuals. To
      test this 'diversity promotes establishment' hypothesis, we introduced colour
      polymorphic pygmy grasshoppers (Tetrix subulata) to different sites in the wild.
      The number of descendants found at the release sites the subsequent year
      increased with increasing number of colour morphs in the founder group, and
      variation in founder groups also positively affected colour morph diversity in
      the established populations. Since colour morphs differ in morphology,
      physiology, behaviour, reproductive life history and types of niche used, these
      findings demonstrate that variation among individuals in functionally important
      traits promotes establishment success under natural conditions, and further
      indicate that founder diversity may contribute to evolutionary rescue and
      increased population persistence.

PMID- 22456886
TI  - A novel mammalian social structure in Indo-Pacific bottlenose dolphins (Tursiops
      sp.): complex male alliances in an open social network.
AB  - Terrestrial mammals with differentiated social relationships live in 'semi-closed
      groups' that occasionally accept new members emigrating from other groups.
      Bottlenose dolphins (Tursiops sp.) in Shark Bay, Western Australia, exhibit a
      fission-fusion grouping pattern with strongly differentiated relationships,
      including nested male alliances. Previous studies failed to detect a group
      membership 'boundary', suggesting that the dolphins live in an open social
      network. However, two alternative hypotheses have not been excluded. The
      community defence model posits that the dolphins live in a large semi-closed
      'chimpanzee-like' community defended by males and predicts that a dominant
      alliance(s) will range over the entire community range. The mating season defence
      model predicts that alliances will defend mating-season territories or sets of
      females. Here, both models are tested and rejected: no alliances ranged over the
      entire community range and alliances showed extensive overlap in mating season
      ranges and consorted females. The Shark Bay dolphins, therefore, present a
      combination of traits that is unique among mammals: complex male alliances in an
      open social network. The open social network of dolphins is linked to their
      relatively low costs of locomotion. This reveals a surprising and previously
      unrecognized convergence between adaptations reducing travel costs and complex
      intergroup-alliance relationships in dolphins, elephants and humans.

PMID- 22456887
TI  - Sex-biased terminal investment in offspring induced by maternal immune challenge
      in the house wren (Troglodytes aedon).
AB  - The reproductive costs associated with the upregulation of immunity have been
      well-documented and constitute a fundamental trade-off between reproduction and
      self-maintenance. However, recent experimental work suggests that parents may
      increase their reproductive effort following immunostimulation as a form of
      terminal parental investment as prospects for future reproduction decline. We
      tested the trade-off and terminal investment hypotheses in a wild population of
      house wrens (Troglodytes aedon) by challenging the immune system of breeding
      females with lipopolysaccharide, a potent but non-lethal antigen. Immunized
      females showed no evidence of reproductive costs; instead, they produced
      offspring of higher phenotypic quality, but in a sex-specific manner. Relative to
      control offspring, sons of immunized females had increased body mass and their
      sisters exhibited higher cutaneous immune responsiveness to phytohaemagglutinin
      injection, constituting an adaptive strategy of sex-biased allocation by immune
      challenged females to enhance the reproductive value of their offspring. Thus,
      our results are consistent with the terminal investment hypothesis, and suggest
      that maternal immunization can induce pronounced transgenerational effects on
      offspring phenotypes.

PMID- 22456888
TI  - Physical competition increases testosterone among Amazonian forager
      horticulturalists: a test of the 'challenge hypothesis'.
AB  - The challenge hypothesis posits that acute increases in testosterone (T) during
      male-male competition enhance performance and survivability while limiting the
      physiological costs of consistently high T. Human challenge hypothesis research
      focuses on young men in industrial populations, who have higher baseline T levels
      than men in subsistence populations. We tested whether the Tsimane,
      pathogenically stressed forager-horticulturalists of the Bolivian Amazon, would
      express acute T increases in response to physical competition. Saliva was
      collected from 88 Tsimane men (aged 16-59 years) before and after a competitive
      soccer match. Tsimane men had significantly lower baseline levels of T (beta = 
      0.41, p < 0.001) when compared with age-matched United States (US) males. Linear
      mixed-effects models were used to establish that T increased significantly
      immediately following competition (beta = 0.23, p < 0.001), remaining high 1 h
      later (beta = 0.09, p = 0.007); equivalent to 30.1 and 15.5 per cent increases in
      T, respectively. We did not find larger increases in T among winners (p = 0.412),
      although T increases were positively associated with self-rated performance (beta
      = 9.07, p = 0.004). These results suggest that despite lower levels of T than US
      males, Tsimane males exhibit acute increases in T at the same relative magnitude
      reported by studies in industrialized settings, with larger increases in T for
      those who report better individual performance.

PMID- 22456889
TI  - Life-history theory, chronic childhood illness and the timing of first
      reproduction in a British birth cohort.
AB  - Life-history theoretical models show that a typical evolutionarily optimal
      response of a juvenile organism to high mortality risk is to reach reproductive
      maturity earlier. Experimental studies in a range of species suggest the
      existence of adaptive flexibility in reproductive scheduling to maximize fitness
      just as life-history theory predicts. In humans, supportive evidence has come
      from studies comparing neighbourhoods with different mortality rates, historical
      and cross-cultural data. Here, the prediction is tested in a novel way in a large
      (n = 9099), longitudinal sample using data comparing age at first reproduction in
      individuals with and without life-expectancy-reducing chronic disease diagnosed
      during childhood. Diseases selected for inclusion as chronic illnesses were those
      unlikely to be significantly affected by shifting allocation of effort away from
      reproduction towards survival; those which have comparatively large effects on
      mortality and life expectancy; and those which are not profoundly disabling. The
      results confirmed the prediction that chronic disease would associate with early
      age at first reproduction: individuals growing up with a serious chronic disease
      were 1.6 times more likely to have had a first child by age 30. Analysis of
      control variables also confirmed past research findings on links between being
      raised father-absent and early pubertal development and reproduction.

PMID- 22456890
TI  - Tradeoffs limit the evolution of male traits that are attractive to females.
AB  - Tradeoffs occur between a variety of traits in a diversity of organisms, and
      these tradeoffs can have major effects on ecological and evolutionary processes.
      Far less is known, however, about tradeoffs between male traits that affect mate
      attraction than about tradeoffs between other types of traits. Previous results
      indicate that females of the variable field cricket, Gryllus lineaticeps, prefer
      male songs with higher chirp rates and longer chirp durations. In the current
      study, we tested the hypothesis that a tradeoff between these traits affects the
      evolution of male song. The two traits were negatively correlated among full
      sibling families, consistent with a genetically based tradeoff, and the tradeoff
      was stronger when nutrients were limiting. In addition, for males from 12
      populations reared in a common environment, the traits were negatively correlated
      within populations, the strength of the tradeoff was largely invariant across
      populations, and the within-population tradeoff predicted how the traits have
      evolved among populations. A widespread tradeoff thus affects male trait
      evolution. Finally, for males from four populations assayed in the field, the
      traits were negatively correlated within and among populations. The tradeoff is
      thus robust to the presence of environmental factors that might mask its effects.
      Together, our results indicate there is a fundamental tradeoff between male
      traits that: (i) limits the ability of males to produce multiple attractive
      traits; (ii) limits how male traits evolve; and (iii) might favour plasticity in
      female mating preferences.

PMID- 22456892
TI  - Toward highly efficient CdS/CdSe quantum dots-sensitized solar cells
      incorporating ordered photoanodes on transparent conductive substrates.
AB  - A series of ordered photoanodic architectures (including ordered TiO(2) nanotube
      arrays (TNT), ZnO nanorods, ZnO/TiO(2) core/shell nanostructures) for CdS/CdSe
      sensitized solar cells (QDSCs), were fabricated directly on transparent
      conductive oxide glasses by a facile sol-gel assisted template process. The
      morphologies, optical and electrical properties of TNTs and CdS/CdSe co
      sensitized TNTs have been demonstrated. The effect of CdSe deposition time on the
      cell performance was clarified, and the growth mechanism of the CdSe quantum dots
      on the surface of the TNTs has been proposed as well. Furthermore, the evolution
      of open-circuit photovoltage (V(oc)) towards CdSe deposition time has been
      investigated by electrochemical impedance spectroscopy (EIS). A promising light
      to-electricity conversion efficiency of up to 4.61% has been achieved with 3 MUm
      long TNT arrays, which is the best record for sandwich-type ordered TNT-based
      QDSCs.

PMID- 22456893
TI  - The prognostic value of serum methotrexate area under curve in elderly primary
      CNS lymphoma patients.
AB  - Studies on pharmacokinetics and pharmacodynamics of high-dose methotrexate
      chemotherapy (HD-MTX) in elderly primary central nervous system lymphoma (PCNSL)
      patients are rare. MTX exposure time has recently been proposed as an outcome
      determining factor in PCNSL. We investigated 49 immunocompetent PCNSL patients
      (female N=30, male N=19, median age 73 years) who were treated according to HD
      MTX-based protocols. A two-compartment pharmacokinetic model was used to describe
      the MTX clearance. Response to treatment was assessed by MRI. We used
      multivariable models to investigate the association between MTX exposure and
      tumor response as well as survival. Dose normalized MTX peak serum levels [C
      (max), MUmol/L g] and dose normalized area under the curve [AUC(dn), MUmol h/L g]
      were higher in females than in males, respectively [59.4 (f) vs. 48.1 (m),
      P<0.001; 373.2 (f) vs. 271.9 (m), P=0.008]. Increasing AUC was inversely
      correlated with tumor response. AUC values above 2,126 h MUmol/L were
      independently associated with shorter overall and progression-free survival
      [hazard ratio (HR), 4.56, 95 % CI 1.74-11.94; HR 2.87, 95 % CI 1.18-7.00].
      Exceedingly high MTX AUC levels can have a negative impact on progression-free
      and overall survivals in elderly PCNSL patients.

PMID- 22456894
TI  - A condensed phenylpropanoid glucoside and pregnane saponins from the roots of
      Hemidesmus indicus.
AB  - From the roots of Hemidesmus indicus, one new condensed phenylpropanoid glucoside
      and three new pregnenolone glycosides, named hemidesmosides A-C, were isolated
      along with one known related compound, plocoside A.

PMID- 22456895
TI  - Cyclic diarylheptanoids as inhibitors of NO production from Acer nikoense.
AB  - We prepared a series of acerogenins A and B derivatives as inhibitors of nitric
      oxide (NO) production in vitro. Our results suggested that an ester group at a
      hydroxyl at C-2 improved inhibitory effects without cytotoxicity. A benzoyl ester
      derivative of acerogenin C showed the most potent inhibitory activity of NO
      production from lipopolysaccharide-activated macrophages.

PMID- 22456896
TI  - Samuel Goldflam (1852-1932).

PMID- 22456897
TI  - A small molecule sensor for fluoride based on an autoinductive, colorimetric
      signal amplification reaction.
AB  - This article describes a small molecule reagent that is capable of detecting
      fluoride down to 0.12 mM (2.3 ppm) in water. The reagent reveals this level of
      fluoride through a novel autoinductive signal amplification reaction that
      produces an unambiguous colorimetric readout.

PMID- 22456898
TI  - Integrated microring resonator sensor arrays for labs-on-chips.
AB  - Planar waveguide optical ring resonators have shown great potential as compact
      and sensitive biochemical sensors. Advances in integrated optics based on Si
      technologies have allowed researchers to integrate multiple micron-sized ring
      resonator sensors with other optical and fluidic functions on Si chips using mass
      production techniques. Recent demonstrations of clinically relevant analyte
      detection by MRR sensor arrays have moved this technology closer to
      commercialization. Here, a survey of the development of microring sensor arrays
      for lab-on-a-chip applications is presented and illustrated with state-of-the-art
      examples.

PMID- 22456899
TI  - A metallomics approach discovers selenium-containing proteins in selenium
      enriched soybean.
AB  - Our previous study found that high-molecular-weight selenium (Se) species make up
      82% of the total Se in the bean of Se-enriched soybean plants (Chan et al. 2010,
      Metallomics, 2(2): p. 147-153). The Se species have been commonly seen in other
      plants in addition to soybean, but their identities remain unresolved. The
      present study employs a multi-technique metallomics approach to characterize the
      proteins containing Se in the beans of Se-enriched soybean plants. Two main
      categories of proteins, maturation proteins and protease inhibitors, were found
      in Se-containing high-performance liquid chromatography (HPLC) fractions. The
      proteins were screened by two-dimensional HPLC-inductively coupled plasma mass
      spectrometry, size-exclusion chromatography, and anion-exchange chromatography,
      and the Se-containing fractions were then identified by peptide mapping using
      HPLC-Chip-electrospray ion trap mass spectrometry. Based on the belief that Se
      goes into proteins through non-specific incorporation, a new method was designed
      and applied for the Se-containing peptide identification. The Se-containing
      peptide KSDQSSSYDDDEYSKPCCDLCMCTRS, part of the sequence of protein Bowman-Birk
      proteinase isoinhibitor (Glycine max), was found in one of the Se-containing
      fractions. The nutritional value of the Se-containing proteins in Se-enriched
      soybeans will be an interesting topic for the future studies.

PMID- 22456900
TI  - Porcine testicular extract inhibits T cell proliferation by blocking cell cycle
      transition from G1 phase to S phase.
AB  - Since T cells express diverse sex steroid hormone receptors, they might be a good
      model to evaluate the effects of sex steroid hormones on immune modulation.
      Porcine testicular extract contains several sex steroid hormones and may be
      useful to study the effects of sex steroid hormones during T cell activation. We
      have examined the effects of the porcine testicular extract on T cell activation:
      proliferation and secretion of cytokines (IL-2 and IFN-gamma) by activated T
      cells were severely decreased after treatment with porcine testicular extract.
      The extract produced an immunosuppressive effect and inhibited the proliferation
      of activated T cells by blocking the cell cycle transition from the G(1) phase to
      S phase. These effects were mediated by a decrease in the expression of cyclin D1
      and cyclin E and constitutive expression of p27(KIP1) after T cell activation.

PMID- 22456901
TI  - Changes in the expression of serum markers CA242, CA199, CA125, CEA, TNF-alpha
      and TSGF after cryosurgery in pancreatic cancer patients.
AB  - The presence of serum tumor markers, carbohydrate antigen 242 (CA242),
      carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125),
      carcinoembryonic antigen (CEA), tumor-supplied group of factors (TSGF) and tumor
      necrosis factor-alpha (TNF-alpha), is closely associated with invasion and
      metastasis of many malignancies. The expression of these markers were measured in
      serum taken from 37 pancreatic cancer patients prior to treatment. Levels of
      CA242, CA199, CA125, CEA and TNF-alpha expression correlated with tumor size,
      clinical stage, tumor differentiation, lymph node and liver metastasis (P <
      0.05). One month after cryosurgery, serum levels of these markers were
      significantly reduced compared with levels prior to cryosurgery (P < 0.05),
      whereas there was no significant difference was found between serum levels before
      and after chemotherapy (P > 0.05). Thus, cryosurgery is more effective than
      chemotherapy for decreasing CA242, CA199, CA125, CEA, TSGF and TNF-alpha serum
      levels in these patients.

PMID- 22456902
TI  - Biotransformation of isonitrosoacetophenone (2-keto-2-phenyl-acetaldoxime) in
      tobacco cell suspensions.
AB  - Nicotiana tabacum cell suspensions, 2 g wet wt/ml, rapidly took up 1 mM
      isonitrosoacetophenone (INAP), a plant-derived stress metabolite with anti
      oxidative and anti-fungal properties, producing 4'-hexopyranosyloxy-3'
      methoxyisonitrosoacetophenone in 54 % yield over 18 h. Unconverted INAP was at 33
      MUM. UPLC-MS/MS analyses with MassFragment software were used for metabolite
      identification. INAP had been hydroxylated at its meta- and para-positions as
      well as undergoing subsequent methoxylation and glycosylation. INAP is thus
      recognized by the enzymatic machinery of the phenylpropanoid pathway and is
      converted to a molecule with a substitution pattern similar to ferulic acid.

PMID- 22456903
TI  - NahK/GlmU fusion enzyme: characterization and one-step enzymatic synthesis of UDP
      N-acetylglucosamine.
AB  - The availability of uridine 5'-diphosphate N-acetylglucosamine (UDP-GlcNAc) is a
      prerequisite for the GlcNAc-transferase-catalyzed glycosylation reaction. UDP
      GlcNAc has already been synthesized using an N-acetylhexosamine 1-kinase (NahK)
      and a GlcNAc-1-P uridyltransferase (truncated GlmU) and here, a fusion enzyme was
      constructed with truncated GlmU and NahK. After determination of the optimum
      catalytic condition (pH 8.0 at 40  degrees C), the fusion enzyme was used to
      synthesize UDP-GlcNAc in a single step with a yield of 88 % from GlcNAc, ATP and
      UTP. Furthermore, a simplified purification method was demonstrated using
      separation by gel filtration after by-product digestion with alkaline
      phosphatase. An overall yield of 77 % and a purity of over 90 % were achieved.

PMID- 22456904
TI  - Enhanced expression of recombinant human cyclooxygenase 1 from stably-transfected
      Drosophila melanogaster S2 cells by dimethyl sulfoxide is mediated by up
      regulation of nitric oxide synthase and transcription factor Kr-h1.
AB  - Recombinant human cyclooxygenase 1 (COX-1) was expressed from stably-transfected
      Drosophila melanogaster S2 (S2) cells. DMSO improved the expression of
      recombinant COX-1 by 180 %. DMSO increased the expression of nitric oxide
      synthase (NOS) at both the RNA and protein levels; NOS expression was closely
      correlated with the synthesis of recombinant COX-1 mRNA in stably-transfected S2
      cells. DMSO also induced the gene encoding Kr-h1 which binds to the CACCC element
      of the metallothionein promoter to enhance the expression of recombinant COX-1.
      Therefore, DMSO improves the expression of recombinant COX-1 via NOS and/or the
      transcription factor Kr-h1.

PMID- 22456905
TI  - Immunomodulatory efficiency of poly(2-oxazolines).
AB  - Poly(2-oxazolines) represent promising polymer materials for biomedical
      applications. The activation of mouse lymphoid macrophage line P388.D1 (clone
      3124) by two selected representatives of poly(2-oxazolines), namely poly(2-ethyl
      2-oxazoline) (PETOX100) and poly[2-(4-aminophenyl)-2-oxazoline-co-2-ethyl-2
      oxazoline] (AEOX10), was assessed in vitro. The immunomodulatory efficacy of both
      polymers was evaluated via the induced release of pro-inflammatory cytokines (TNF
      alpha, IL-1alpha and IL-6) and the acceleration of reactive free radicals. The
      present study revealed effective structure-immunomodulating associations of
      AEOX10 and PETOX100, which are desirable in biomedical and pharmaceutical
      applications of aliphatic and aromatic poly (2-oxazolines) in vivo.

PMID- 22456906
TI  - Schizophrenia genetics: putting all the pieces together.
AB  - Schizophrenia is a major mental disorder characterized by a deep disruption of
      the thinking process and of emotional response. For many decades, genetics
      studies have yielded little success in identifying genetic factors responsible
      for the disease. However, with the recent breakthroughs in genome analysis
      technologies, the field of the genetics of schizophrenia has progressed a lot in
      the last years. Both common and rare variants have been successfully associated
      with the disease and a particular emphasis has been made on rare copy number
      variations. Recently, a new paradigm linking de novo mutations to the genetic
      mechanism of schizophrenia has been unravelled. The aim of this review is to
      discuss the most important genetic studies made in the field to give a general
      perspective of where to go in the future.

PMID- 22456907
TI  - Serum IL-31 levels are increased in patients with cutaneous T-cell lymphoma.

PMID- 22456909
TI  - Complete genome sequence of the first Andean strain of potato virus S from Brazil
      and evidence of recombination between PVS strains.
AB  - An isolate of the Andean strain of potato virus S (PVS), named BB-AND, was
      detected for the first time in a Brazilian potato crop, fully sequenced and
      analyzed. A comparison of BB-AND with other PVS isolates (Andean and Ordinary)
      showed that BB-AND is quite distinct. The lowest amino acid sequence identity to
      the only other fully sequenced Andean isolate was found in ORF 1 (82%) and ORF 6
      (87%). Recombination analysis showed that the isolate Vltava (AJ863510), from
      Germany, is a recombinant between PVS(O) and PVS(A) isolates, with the
      recombination event located between nucleotides 6125 and 8324.

PMID- 22456910
TI  - Characterization of the complete genome of ribgrass mosaic virus isolated from
      Plantago major L. from New Zealand and Actinidia spp. from China.
AB  - The complete genomes of tobamovirus isolates from Plantago major L. from New
      Zealand (NZ-439), Plantago sp. from Germany (Kons 1105), Actinidia chinensis
      (Actinidia-AC) and A. deliciosa (Actinidia-AD) from China were sequenced and
      compared to previously published tobamovirus genomes. Their genome organization
      and phylogenetic analysis of the putative replicase component, replicase
      readthrough component, movement protein, coat protein and complete genome placed
      all four isolates in subgroup 3 of the tobamoviruses. The complete genomes
      differed from each other by <8.5% and from published sequences of turnip vein
      clearing virus and youcai mosaic virus by about 12-13% and 19-20%, respectively.
      The aa sequences of the individual ORFs of the Plantago and Actinidia isolates
      differed from each other by <4% and were most similar to published (partial)
      sequences of ribgrass mosaic virus (RMV). We propose that these sequences
      constitute the first complete published sequences for RMV.

PMID- 22456911
TI  - Development of a multiplex polymerase chain reaction for simultaneous detection
      of wheat viruses and a phytoplasma in China.
AB  - Barley yellow dwarf viruses (BYDVs, mainly consisting of three strains, GAV, GPV
      and PAV, in China), barley stripe mosaic virus (BSMV), wheat yellow mosaic virus
      (WYMV), wheat dwarf virus (WDV) and wheat blue dwarf phytoplasma (WBD) constitute
      a group of major wheat pathogens that have caused huge yield losses but are
      scarcely distinguished by their phenotype alone. For the simultaneous detection
      and discrimination of these seven pathogens in wheat, a multiplex polymerase
      chain reaction (M-PCR) method was developed in this study through a series of
      parameter optimizations. Detection and sensitivity tests using samples collected
      from the field indicate that the M-PCR method can rapidly, simultaneously and
      relatively effectively detect BYDV-GAV, -GPV, -PAV, BSMV, WYMV, WDV and WBD.

PMID- 22456913
TI  - [Basics of tumor development and importance of human papilloma virus (HPV) for
      head and neck cancer].
AB  - Head and Neck Squamous Cell Carcinoma (HNSCC) are the 6th most common cancers
      worldwide. While the incidence of larynx-hypopharynx carcinoma decreases,
      actually an increase in oropharyngeal squamous cell carcinoma (OSCC) is observed.
      Classical risk factors for HNSCC are smoking and alcohol. Though, it was shown
      recently for 25 to 60% of OSCC, to be associated with an infection by oncogenic
      human papilloma virus (HPV). The development of "common" head-neck-tumors is
      substantially enhanced by an accumulation of genetic changes, which lead to an
      inactivation of tumor suppressor genes or to an activation of proto-oncogenes. A
      more or less uniform sequence of different DNA-damages leads to genetic
      instability. In this context, an early and frequent event is deletion on the
      short arm of chromosome 9, which results in inactivation of the p16-gene. On the
      contrary, for HPV-induced carcinogenesis, expression of the viral proteins E6 and
      E7 is most important, since E6 and E7 lead to inactivation of the cellular tumor
      suppressor-proteins p53 and Rb. The process of natural transoral infection is not
      yet clear. However, as a matter of fact peroral HPV-infection is not seldom and
      in most cases such an infection heals completely and uneventfully. Smoking seems
      to increases the probability for developing an HPV-associated tumor. The
      association of HNSCC with HPV can be proven with established methods in clinical
      diagnostics. In addition to classical prognostic factors, diagnosis of an HPV
      association may become important for future therapies. Prognostic relevance of
      HPV probably surmounts many known risk-factors, for instance regional metastasis.
      Until now, no other molecular markers are established in clinical routine. Future
      therapy concepts may vary for the two subgroups of patients, especially patients
      with HPV-associated OSCC may take advantage of a less aggressive postoperative
      treatment. Finally an outlook will be given on possible target-aimed therapies,
      of which so far only antibodies against EGF-receptors are established in clinical
      practice.

PMID- 22456912
TI  - Household income and spiritual well-being but not body mass index as determinants
      of poor self-rated health among African American adolescents.
AB  - Very little is known about predictors of subjective health status among African
      American adolescents. This study was designed to determine whether selected
      anthropometric, psychological, lifestyle behavioral, and structural variables
      predicted poor self-rated general health in a cross-sectional nonclinical sample
      of 310 female African American adolescents, 14-18 years old. The odds of
      reporting poor self-rated health were 2-3 times greater for African American
      teens from lower socioeconomic households when compared to teens residing in
      higher socioeconomic households and for those reporting infrequent participation
      in activities that promote spiritual well-being compared to those who participate
      more frequently in activities that enhance spiritual health. Findings indicate
      that socioeconomic level and engagement in behaviors that enhance healthy
      spirituality appear to be the most salient predictors of self-rated health. In
      addition to biodiversity considerations that influence perceptions of health
      status, culturally focused interventions should integrate variables shown to
      influence self-rated health among African American teens. These inclusions may
      inform a more integrated understanding of health, health outcomes, and health
      disparities in this vulnerable population.

PMID- 22456914
TI  - [Current advances in diagnosis and surgical treatment of lymph node metastasis in
      head and neck cancer].
AB  - Still today, the status of the cervical lymph nodes is the most important
      prognostic factor for head and neck cancer. So the individual treatment concept
      of the lymphatic drainage depends on the treatment of the primary tumor as well
      as on the presence or absence of suspect lymph nodes in the imaging diagnosis.
      Neck dissection may have either a therapeutic objective or a diagnostic one. The
      selective neck dissection is currently the method of choice for the treatment of
      patients with advanced head and neck cancers and clinical N0 neck. For oncologic
      reasons, this procedure is generally recommended with acceptable functional and
      aesthetic results, especially under the aspect of the mentioned staging
      procedure. In this review article, current aspects on pre- and posttherapeutic
      staging of the cervical lymph nodes are described and the indication and the
      necessary extent of neck dissection for head and neck cancer is discussed.
      Additionally the critical question is discussed if the lymph node metastasis
      bears an intrinsic risk of metastatic development and thus its removal in a most
      possible early stage plays an important role.

PMID- 22456915
TI  - [Current strategies in radiotherapy of head- and neck cancer].
AB  - Over the last 20 years there was a dramatic change in therapeutic options for
      head and neck tumors mainly due to improvements in surgical and radiotherapeutic
      techniques and in the increasing use of multimodal therapy. Especially for
      locally advanced tumors, one can achieve long lasting disease free intervals in a
      large proportion of patients. The following article will focus on the novel
      techniques in radiation oncology and combined radiochemotherapy giving an
      overview without too many technical details.

PMID- 22456917
TI  - [Systemic therapy strategies for head-neck carcinomas: current status].
AB  - Head and neck cancers, most of which are squamous cell tumours, have an
      unsatisfactory prognosis despite intensive local treatment. This can be
      attributed, among other factors, to tumour recurrences inside or outside the
      treated area, and metastases at more distal locations. These tumours therefore
      require not only the standard surgical and radiation treatments, but also
      effective systemic treatment. The main option here is antineoplastic
      chemotherapy, which is firmly established in the palliative treatment of
      recurrent or metastatic stages of disease, and is used with curative intent in
      the form of combined simultaneous or adjuvant chemoradiotherapy in patients with
      inoperable or advanced tumour stages. Neoadjuvant treatment strategies for tumour
      reduction before surgery have yet to gain acceptance. Induction chemotherapy
      protocols before radiotherapy have to date been used in patients at high risk of
      distant metastases or as an aid for decision-making ("chemoselection") in those
      with extensive laryngeal cancers, prior to definitive chemoradiotherapy or
      laryngectomy. Triple-combination induction therapy (taxanes, cisplatin, 5
      fluorouraeil) shows high remission rates with significant toxicity and, in
      combination with (chemo-)radiotherapy, is currently being compared with
      simultaneous chemoradiotherapy the current gold standard with regards to efficacy
      and long-term toxicity. A further systemic treatment strategy, called 'targeted
      therapy', has been developed to help increase specificity and reduce toxicity. An
      example of targeted therapy, EGFR-specific antibodies, can be used in palliative
      settings and, in combination with radiotherapy, to treat advanced head and neck
      cancers. A series of other novel biologicals such as signal cascade inhibitors,
      genetic agents, or immunotherapies, are currently being evaluated in large-scale
      clinical studies, and could prove useful in patients with advanced, recurring or
      metastatic head and neck cancers. When developing a lasting, individualised
      systemic tumour therapy, the critical evaluation criteria are not only efficacy
      and acute toxicity but also (Iong-term) quality-of-life and the identification of
      dedicated predictive biomarkers.

PMID- 22456916
TI  - [Supportive therapy in medical therapy of head and neck tumors].
AB  - Fever during neutropenia may be a symptom of severe life threatening infection,
      which must be treated immediately with antibiotics. If signs of infection
      persist, therapy must be modified. Diagnostic measures should not delay
      treatment. If the risk of febrile neutropenia after chemotherapy is >= 20%, then
      prophylactic therapy with G-CSF is standard of care. After protocols with a risk
      of febrile neutropenia of 10-20%, G-CSF is necessary, in patients older than 65
      years or with severe comorbidity, open wounds, reduced general condition. Anemia
      in cancer patients must be diagnosed carefully, even preoperatively. Transfusions
      of red blood cells are indicated in Hb levels below 7-8 g/dl. Erythropoiesis
      stimulating agents (ESA) are recommended after chemotherapy only when hemoglobin
      levels are below 11 g/dl. The Hb-level must not be increased above 12 g/dl.
      Anemia with functional iron deficiency (transferrin saturation < 20%) should be
      treated with intravenous iron, as oral iron is ineffective being not absorbed.
      Therapy of pain must follow diagnostic and treatment standards. Nausea or emesis
      following chemotherapy can be classified as minimal, low, moderate and high. The
      antiemetic prophylaxis should be escalated accordingly. In chemotherapy with low
      emetogenic potential steroids are sufficient, in the moderate level 5-HT3
      receptor antagonists (setrons) are added, and in the highest level Aprepitant as
      third drug.

PMID- 22456918
TI  - [Current oncologic concepts and emerging techniques for imaging of head and neck
      squamous cell cancer].
AB  - The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and
      currently they account for 5% of all malignancies worldwide. Inspite of ongoing
      developments in diagnostic imaging and new therapeutic facilities, HNSCC still
      represents a multidisciplinary challenge. One of the most important prognostic
      factors in HNSCC is the presence of lymph node metastases. Patients with
      confirmed nodal involvement have a considerable reduction of their 5-year overall
      survival rate. In the era of individually optimised surgery, chemotherapy and
      intensity modulated radiotherapy, the main role of pre- and posttherapeutic
      imaging remains cancer detection at an early stage and accurate follow-up. The
      combined effort of early diagnosis and close patient monitoring after surgery
      and/or radio-chemotherapy influences disease progression and outcome prediction
      in patients with HNSCC. This review article focuses on currrent oncologic
      concepts and emerging tools in imaging of head and neck squamous cell cancer.
      Besides the diagnostic spectrum of the individual imaging modalities, their
      limitations are also discussed. One main part of this article is dedicated to PET
      CT which combines functional and morphological imaging. Furthermore latest
      developments in MRT are presented with regard to lymph node staging and response
      prediction. Last but not least, a clinical contribution in this review explains,
      which information the head and neck surgeon requires from the multimodality
      imaging and its impact on operation planning.

PMID- 22456919
TI  - [Preservation of organ function in head and neck cancer].
AB  - Preservation of function is a crucial aspect for the evaluation of therapies
      applied in the field of head and neck cancer. However, preservation of anatomic
      structures does not equalize preservation of function. Particularly for the
      evaluation of alternative treatment options with equivalent oncologic outcome
      functional outcome becomes increasingly important. Present studies collect with
      varying emphasize (1) the effects of therapy on essential body functions, (2)
      additional therapy-induced toxic effects, and (3) health-related quality of life.
      The present article summarizes vital aspects of clinical research from the last
      years. Preservation of function after surgical and non-surgical treatment
      approaches are presented according to tumour localisation and staging criteria.
      Additional methodological aspects of study design and documentation as well as
      challenges and present activities for the transformation into clinical practise
      are discussed.

PMID- 22456920
TI  - [Traditional transcutaneous approaches in head & neck surgery].
AB  - The treatment of laryngeal and hypopharyngeal malignancies remains a challenging
      task for the head and neck surgeon as the chosen treatment modality often has to
      bridge the gap between oncologically sound radicality and preservation of
      function. Due to the increase in transoral laser surgery in early tumor stages
      and chemoradiation in advanced stages, the usage of traditional transcutaneous
      approaches has decreased over the recent past. In addition, the need for a
      function-sparing surgical approach as well as highest possible quality of life
      has become evident. In view of these facts, rationale and importance of
      traditional transcutaneous approaches to the treatment of laryngeal and
      hypopharyngeal malignancies are discussed in a contemporary background. The
      transcutaneous open partial laryngectomies remain a valuable tool in the
      surgeon's armamentarium for the treatment of early and advanced laryngeal
      carcinomas, especially in cases of impossible laryngeal overview using the rigid
      laryngoscope. Open partial laryngetomies offer superior overview and oncologic
      safety at the anterior commissure, especially in recurrencies. In select advanced
      cases and salvage settings, the supracricoid laryngectomy offers a valuable tool
      for function-preserving but oncologically safe surgical therapy at the cost of
      high postoperative morbidity and a very demanding rehabilitation of swallowing.
      In hypopharyngeal malignancies, the increasing use of transoral laser surgery has
      led to a decline in transcutaneous resections via partial pharyngectomy with
      partial laryngectomy in early tumor stages. In advanced stages of tumors of the
      piriform sinus and the postcricoid area with involvement of the larynx, total
      laryngectomy with partial pharyngectomy is an oncologically safe approach. The
      radical surgical approach using circumferent laryngopharyngectomy with/without
      esophagectomy is indicated in salvage cases with advanced recurrences or as a
      primary surgical approach in patients where chemoradiation does not offer
      sufficient oncologic control or preservation of function. In cases with impending
      reconstruction, fasciocutaneous free flaps (anterolateral thigh flap, radial
      forearm flap) seem to offer superior results to enteric flaps in cases where the
      cervical esophagus is not involved leading to better voice rehabilitation with
      fewer complications and postoperative morbidity. In salvage situations, the
      Gastroomental Free Flap has proven to be a valuable tool. In conclusion, the
      choice of a surgical treatment modality is influenced by the patient's anatomy,
      tumor size and location as well as the surgeon's personal expertise.

PMID- 22456921
TI  - [Transoral treatment strategies in head and neck tumors].
AB  - The introduction of transoral endoscopic surgery resulted in a significant
      reduction of surgical trauma and a paradigm change from transcervical to
      transoral surgical treatment in head and neck tumors. In selected cases minimally
      invasive transoral resections allow a reduction of morbidity without
      deteriorating oncological results. Thus, transoral surgical techniques gained
      more acceptance, led to an extension of the indications and technologies as well
      as an improvement of surgical instruments.Depending on the anatomical
      localization transoral treatment strategies and their indications are described
      and relevant literature is discussed according to new developments and results.

PMID- 22456923
TI  - Recombinant human phospholipase C zeta 1 induces intracellular calcium
      oscillations and oocyte activation in mouse and human oocytes.
AB  - BACKGROUND: Oocyte activation is a crucial step that comprises the release of the
      oocyte from meiotic arrest, pronuclear formation and subsequent embryo
      development. Oocytes are activated by repetitive increases in the intracellular
      concentration of free Ca(2+), [Ca(2+)](i) oscillations, which are triggered
      during fertilization by the introduction of the sperm-specific phospholipase C
      zeta 1 (PLCZ1). Recent studies have shown that sperm from patients lacking
      expression of PLCZ1 or expressing mutant forms of PLCZ1 fail to induce
      [Ca(2+)](i) oscillations or oocyte activation. We first purified recombinant
      human PLCZ1 (hPLCZ1) protein and evaluated its [Ca(2+)](i) oscillation activity
      in mouse and human oocytes with the view to investigate its application in the
      clinic for assisted oocytes activation in lieu of chemical agents. METHODS:
      Recombinant hPLCZ1 was synthesized using the Escherichia coli system, and
      subjected to immunoblot analysis with anti-PLCZ1 and anti-His tag antibodies.
      [Ca(2+)](i) oscillations by microinjection of recombinant hPLCZ1 into mouse or
      human oocytes were examined by [Ca(2+)](i) monitoring with Fluo 4. Ploidy of the
      oocytes with recombinant hPLCZ1 injection was confirmed with fluorescence in situ
      hybridization. RESULTS: A band of 68 kDa on recombinant protein was detected with
      both antibodies. Injection of recombinant hPLCZ1 induced [Ca(2+)](i) oscillations
      in a dose-dependent manner in both mouse and human oocytes. These oscillations,
      which closely resembled those initiated by the sperm upon fertilization,
      triggered activation and cleavage in oocytes of both species, although further
      development of the mice embryos was low. U73122, a PLC inhibitor, blocked the
      ability of hPLCZ1 to initiate oscillations. Microinjection of recombinant hPLCZ1
      into ICSI-failed human oocytes rescued fertilization failure in five of eight
      attempts. CONCLUSIONS: Repeated [Ca(2+)](i) oscillations and oocyte activation
      were induced in mouse and human oocytes by microinjection of recombinant hPLCZ1
      synthesized in E. Coli. Injection of recombinant protein could thus provide a
      biological solution for inducing artificial activation of oocytes.

PMID- 22456922
TI  - Isolated primate primordial follicles require a rigid physical environment to
      survive and grow in vitro.
AB  - BACKGROUND: In vitro follicle growth is a promising fertility preservation
      strategy in which ovarian follicles are cultured to produce mature and
      fertilization-competent oocytes. However, in primates, there has been limited
      success with in vitro follicle growth starting from primordial and primary
      follicles because adequate isolation methods and culture strategies have not been
      established. Understanding how to use primordial follicles for fertility
      preservation has significant implications because these follicles are the most
      abundant in the ovary, are found in all females and are fairly resistant to
      cryopreservation and chemotherapeutics. METHODS: In the primate ovary, primordial
      follicles are concentrated near the collagen-rich ovarian cortex. To obtain these
      follicles, we separated the ovarian cortex prior to enzymatic digestion and
      enriched the primordial follicle concentration by using a novel double filtration
      system. To test the hypothesis that a rigid physical environment, as found in
      vivo, is optimal for survival, primordial follicles were cultured in different
      concentrations of alginate for up to 6 days. Follicle survival and morphology
      were monitored throughout the culture. RESULTS: We found that primate ovarian
      tissue can be maintained for up to 24 h at 4 degrees C without compromising
      tissue or follicle health. Hundreds of intact and viable primordial follicles
      were isolated from each ovary independent of animal age. Follicle survival and
      morphology were more optimal when follicles were cultured in 2% alginate compared
      with 0.5% alginate. CONCLUSIONS: By mimicking the rigid ovarian environment
      through the use of biomaterials, we have established conditions that support
      primordial follicle culture. These results lay the foundations for studying the
      basic biology of primordial follicles in a controlled environment and for using
      primordial follicles for fertility preservation methods.

PMID- 22456924
TI  - Non-mass-like lesions on breast ultrasonography: a systematic review.
AB  - This article reviews various non-mass-like ultrasonography (US) findings of the
      breast and the sonographic-pathologic correlation with Doppler techniques,
      elastography, and MRI. High-resolution US allows for identification of small,
      clinically occult non-mass-like US findings. Ductal carcinoma in situ and
      invasive lobular carcinoma usually manifest as a non-mass-like lesion on US. It
      is useful to classify non-mass-like lesions on US in a similar manner to the
      classification of non-mass-like enhancement on MRI.

PMID- 22456931
TI  - Injectable and thermosensitive PLGA-g-PEG hydrogels containing hydroxyapatite:
      preparation, characterization and in vitro release behavior.
AB  - Here we report the design and characterization of injectable and thermosensitive
      hydrogel composites comprised of poly(lactic acid-co-glycolic acid)-g
      poly(ethylene glycol)(PLGA-g-PEG) containing hydroxyapatite (HA) for potential
      application in bone tissue engineering. Inclusion of HA into the hydrogels would
      provide both enhanced mechanical properties and bioactivity to the composites.
      The effects of HA on the properties of the hydrogels were investigated in terms
      of storage modulus, sol-gel transition properties, pH and in vitro dye release
      behavior. The hydrogel composites were also studied by scanning electron
      microscopy (SEM), x-ray diffraction (XRD) and Fourier transform infrared
      spectroscopy (FTIR). The results revealed that hydrogel composites preserved
      their sol-gel transition properties in the presence of HA. The storage modulus of
      the hydrogels was enhanced in a HA-content dependent manner, and the acidic pH
      environment of the hydrogel was neutralized by HA, both representing great
      advantages over the hydrogel alone. SEM images showed that HA particles were well
      dispersed and distributed within the hydrogel matrix. The composites showed a
      sustained release of a small molecule model dye for up to two weeks with slight
      increase of release with addition of HA. This work demonstrates the formation of
      novel thermogelling composites of PLGA-g-PEG and HA that are injectable and
      promote controlled release.

PMID- 22456936
TI  - Identification of mercury and other metals complexes with metallothioneins in
      dolphin liver by hydrophilic interaction liquid chromatography with the parallel
      detection by ICP MS and electrospray hybrid linear/orbital trap MS/MS.
AB  - A novel analytical procedure for the identification of metal (Hg, Cd, Cu, Zn)
      complexes with individual metallothionein (MT) isoforms in biological tissues by
      electrospray MS/MS was developed. The sample preparation was reduced to three
      rapid steps: the two-fold dilution of the sample cytosol with acetonitrile, the
      recovery of the supernatant containing MT-complexes by centrifugation and its
      concentration under nitrogen flow. The replacement of reversed phase HPLC by
      hydrophilic interaction LC (HILIC) allowed the preservation of the unstable and
      low abundant metallothionein zinc-mercury mixed complexes (MT-Zn(6)Hg). The MT
      complexes eluted were detected by ICP MS and identified in terms of molecular
      mass by electrospray high resolution (100,000) MS. The identification was
      completed by on line demetallation and the determination of the molecular mass of
      the apoform, followed by amino acid sequencing in the top-down mode using high
      energy collision fragmentation (HCD). The method was applied to the
      identification of MT complexes in a white-sided dolphin (Lagenorhynchus acutus)
      liver homogenate. The Zn complex of the N-acetylated MT2 isoform was found to be
      predominant, the presence of mixed complexes with Cd, Cu and, for the first time
      ever, Hg, was demonstrated. The latter finding has the potential to shed new
      light on the mercury detoxification mechanism in marine organisms.

PMID- 22456937
TI  - A simple liquid chromatography-tandem mass spectrometry method to determine
      relative plasma exposures of drug metabolites across species for metabolite
      safety assessments (metabolites in safety testing). II. Application to unstable
      metabolites.
AB  - We previously described a simple liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method to determine relative plasma exposures of drug metabolites
      across species for metabolite safety assessments. It offers time- and resource
      sparing advantages to ascertain metabolite exposure comparisons between humans
      and laboratory animal species for stable metabolites with high confidence. In
      this study, we tested the limitation of the methodology with compounds possessing
      six substituents found in unstable metabolites. Stabilization procedures were
      used, and stabilized samples were compared with untreated samples for structures
      with established stabilization processes. In most cases, the parent compounds
      with established stability were used as the intrinsic stability references except
      in cases in which the metabolite was more stable than the parent compound. Long
      term storage stability of the unstable structures was tested by comparing the
      response ratio of the metabolite to the stability reference compound for multiple
      independent analyses covering the storage duration. Autosampler stability was
      tested using the same response ratio of the reinjections of the reconstituted
      solution overnight over the first injections. The results supported that the
      possibility that an abbreviated LC-MS/MS peak area ratio comparison can be
      applied to epoxide, amide, catechol, and acyl glucuronides to determine the
      relative plasma exposure of drug metabolites across species; but it may not be
      suitable for iminium ions and esters. Stability of suspected unstable metabolites
      can be tested using the methodology described above.

PMID- 22456938
TI  - Lipolytic, proteolytic, and cholesterol-degrading bacteria from the human
      cerumen.
AB  - Cerumen, also known as ear wax, is a yellowish waxy substance secreted from
      specialized glands in the ear canal of mammals. Human cerumen is rich in protein
      (mainly keratin), lipids (long-chain fatty acids), alcohols, squalene, and
      cholesterol. To-date the role of cerumen is not totally clear but it is believed
      to have antimicrobial properties. Here we describe the isolation of multiple
      bacterial species from human cerumen (among them many Staphylococcus spp. and,
      interestingly, multiple Bacillus spp.) showing that many of these bacteria harbor
      biochemical traits enabling them to utilize different cerumen components for
      their growth. We also suggest the existence of microbial consortia.

PMID- 22456940
TI  - Beetroot red (betanin) inhibits vinyl carbamate- and benzo(a)pyrene-induced lung
      tumorigenesis through apoptosis.
AB  - Betanin, also called beetroot red, has been extensively used as a food colorant.
      In this study, the chemopreventive activity of betanin by oral consumption was
      investigated in two mouse lung tumor models. Vinyl carbamate (VC) and
      benzo(a)pyrene (B(a)P) were used to induce lung tumors, and female A/J mice were
      treated with betanin in drinking water. Betanin significantly decreased tumor
      multiplicity and tumor load induced by both carcinogens. Tumor multiplicity and
      tumor load were decreased by 20% and 39% in the VC lung model, and by 46% and 65%
      in the B(a)P lung model, respectively. Betanin reduced the number of CD31+
      endothelial microvessels and increased the expression of caspase-3, suggesting
      that the lung tumor inhibitory effects were through induction of apoptosis and
      inhibition of angiogenesis. Betanin also induced apoptosis through activated
      caspase-3, -7, -9, and PARP in human lung cancer cell lines. Our data show that
      betanin significantly inhibits lung tumorigenesis in A/J mice and merits
      investigation as a chemopreventive agent for human lung cancer.

PMID- 22456941
TI  - Evolution of inflammasome functions in vertebrates: Inflammasome and caspase-1
      trigger fish macrophage cell death but are dispensable for the processing of IL
      1beta.
AB  - Members of the nucleotide binding and oligomerization domain-like receptors
      (NLRs) and the PYD and CARD domain containing adaptor protein (PYCARD) assemble
      into multi-protein platforms, termed inflammasomes, to mediate in the activation
      of caspase-1 and the subsequent secretion of IL-1beta and IL-18, and the
      induction of pyroptotic cell death. While the recognition site for caspase-1 is
      well conserved in mammals, most of the non-mammalian IL-1beta genes cloned so far
      lack this conserved site. We report here that stimulation or infection of
      seabream macrophages (MO) led to the caspase-1-independent processing and release
      of IL-1beta. In addition, several classical activators of the NLRP3 inflammasome
      failed to activate caspase-1 and to induce the processing and release of IL
      1beta. Furthermore, the processing of IL-1beta in seabream MO is not prevented by
      caspase-1 or pan-caspase inhibitors, and recombinant seabream caspase-1 failed to
      process IL-1beta. However, the pharmacological inhibition of caspase-1 impaired
      Salmonella enterica sv. Typhimurium-induced cell death. These results suggest a
      role for the inflammasome and caspase-1 in the regulation of pyroptotic cell
      death in fish and support the idea that its use as a molecular platform for the
      processing of pro-inflammatory cytokines arose after the divergence of fish and
      tetrapods.

PMID- 22456942
TI  - Perceiving transformed movements when using tools.

PMID- 22456943
TI  - Fos protein-like immunoreactive neurons induced by electrical stimulation in the
      trigeminal sensory nuclear complex of rats with chronically injured peripheral
      nerve.
AB  - The rat trigeminal sensory nuclear complex (TSNC) was examined for Fos protein
      like immunoreactive (Fos-LI) neurons induced by electrical stimulation (ES) of
      the lingual nerve (LN) at 2 weeks after injury to the LN or the inferior alveolar
      nerve (IAN). Intensity-dependent increase in the number of Fos-LI neurons was
      observed in the subnucleus oralis (Vo) and caudalis (Vc) of the spinal trigeminal
      tract nucleus irrespective of nerve injury. The number of Fos-LI neurons induced
      by ES of the chronically injured LN at A-fiber intensity (0.1 mA) was
      significantly increased in the Vo but not the Vc. On the other hand, in rats with
      chronically injured IAN, the number of Fos-LI neurons induced by ES of the LN at
      C-fiber intensity (10 mA) was significantly increased in the Vc but not the Vo.
      These results indicated that injury of a nerve innervating intraoral structures
      increased the c-Fos response of Vo neurons to A-fiber intensity ES of the injured
      nerve. A similar nerve injury enhanced the c-Fos response of Vc neurons to C
      fiber intensity ES of a spared uninjured nerve innervating an intraoral territory
      neighboring that of the injured nerve. The present result show that nerve injury
      causes differential effects on c-Fos expression in the Vo and Vc, which may
      explain complexity of neuropathic pain symptoms in clinical cases.

PMID- 22456944
TI  - Orbscan II and double-K method for IOL calculation after refractive surgery.
AB  - BACKGROUND: Precise IOL calculation in post-refractive surgery patients is still
      a challenge for the cataract surgeon. The purpose of this study is to test
      whether adding Orbscan II values into the double-K method improves IOL
      calculation in this group of patients. METHODS: A prospective study with 43 eyes
      previously submitted to refractive surgery that underwent cataract extraction.
      IOL calculation was performed with double-K method. Post-K value was derived from
      Orbscan total-mean power map. The average corneal curvature of the general
      population (43.8D) was used as the pre-K value. Refraction results 30 days after
      surgery were compared with refraction that would be obtained if we used: (1) post
      K values from keratometry, (2) post-K values from topography, and (3) pre-K
      values from Orbscan total-mean power. Anterior chamber depth measures obtained
      with the IOL Master and Orbscan II were compared. RESULTS: Mean postoperative
      spherical equivalent (SE) was -0.25 +/- 1.10 D in eyes submitted to radial
      keratotomy , -1.04 +/- 1.42 D in eyes previously submitted to myopic Lasik, and
      +0.05 +/- 1.76 D in those submitted to hyperopic surgeries. Had we inputted post
      K values derived from keratometer and from topography, we would have obtained
      significantly higher postoperative refractive errors in eyes previously submitted
      to myopic refractive surgery (p < 0.05). Refractions using pre-K derived from the
      central 8 mm Orbscan instead of 43.8 D were similar in all studied groups (p >
      0.05). Anterior chamber depth measured with IOL Master or Orbscan were similar.
      CONCLUSIONS: Orbscan measurements used as the post-K values into the double-K
      method provide a precise IOL calculation, especially in post myopic refractive
      surgery patients.

PMID- 22456946
TI  - Plasma succinylacetone is persistently raised after liver transplantation in
      tyrosinaemia type 1.
AB  - BACKGROUND: Tyrosinaemia type 1 (HT1) is a rare disorder leading to accumulation
      of toxic metabolites such as succinylacetone (SA) and a high risk of
      hepatocellular carcinoma. Children with HT1 traditionally required liver
      transplantation (OLT) and while the need for this has been reduced by the
      introduction of nitisinone some still require OLT. SA inhibits the enzyme
      porphobilinogen (PBG) synthase and its activity can be used as a marker of active
      SA. Elevated urinary SA post OLT has been reported previously. This study
      describes a novel finding of elevated plasma SA following OLT for HT1. METHODS: A
      retrospective analysis was performed of patients treated for HT1 at our
      institution from 1989-2010. RESULTS: Thirteen patients had an OLT for HT1. In
      patients who received nitisinone prior to OLT, mean urinary and plasma SA were
      elevated prior to treatment but normalised by the time of OLT (p <= 0.01). Mean
      PBG synthase activity increased from 0.032 to 0.99 nkat/gHb (ref range 0.58-1.25)
      at the time of OLT (p < 0.01). Mean urinary SA in patients not treated with
      nitisinone was also elevated prior to OLT; plasma levels and PBG synthase
      activity were not available prior to OLT for this group. Following OLT, mean
      urinary and plasma SA were elevated in all for the duration of follow-up and
      associated with low-normal PBG synthase activity. CONCLUSION: Urinary and plasma
      SA levels are elevated following OLT for HT1. Low-normal PBG synthase activity
      suggests the plasma SA may be active. The clinical significance of this is
      unclear.

PMID- 22456947
TI  - Treatment of adolescents with a periacetabular osteotomy after previous pelvic
      surgery.
AB  - BACKGROUND: Although the success of the Bernese periacetabular osteotomy (PAO)
      has been reported for primary dysplasia, there is no study analyzing the
      radiographic, functional, and gait results of the PAO to correct residual hip
      dysplasia after previous pelvic surgery. QUESTIONS/PURPOSES: We assessed (1)
      radiographic and (2) functional and gait outcomes of patients treated with a PAO
      after previous pelvic surgery (PPSx) and compared their results with results of
      patients with no previous surgery (NPSx) to determine whether the PAO was equally
      effective in patients with revision pelvic surgery. METHODS: Twenty-nine
      dysplastic hips in 26 patients (average age, 16.3 years) were included: 13 in the
      PPSx group and 13 in the NPSx group. Radiographic parameters included the lateral
      center-edge angle, acetabular index, and femoral head extrusion index measured
      preoperatively and at 6 months and 1 year. We assessed preoperative and
      postoperative function using the Harris hip score (HHS). Preoperative and
      postoperative gait analysis included the hip abductor impulse. RESULTS:
      Improvements in groups were seen from preoperatively to 1 year postoperatively
      for the lateral center-edge angle, acetabular index, and femoral head extrusion
      index without differences between groups. The modified HHSs improved at 6 months
      and were maintained at 1 year for patients in both groups without differences
      between groups. The hip abductor impulse returned to preoperative values at 6
      months in the NPSx group but not until 1 year in the PPSx group. CONCLUSIONS: The
      Bernese PAO is effective in providing similar final radiographic and functional
      results, however, a trend toward decreased hip flexion and abduction power at 1
      year was seen with previous pelvic surgery.

PMID- 22456948
TI  - Male-produced pheromone of Spathius agrili, a parasitoid introduced for the
      biological control of the invasive emerald ash borer, Agrilus planipennis.
AB  - The braconid wasp, Spathius agrili, has been released in the U.S. as a biocontrol
      agent for the invasive emerald ash borer (Coleoptera: Buprestidae: Agrilus
      planipennis), a destructive pest of ash trees (Fraxinus spp.). We identified and
      synthesized seven male-specific volatile compounds. Three of these, dodecanal,
      (4R,11E)-tetradecen-4-olide, and (Z)-10-heptadecen-2-one, were the key
      behaviorally active components in flight tunnel bioassays. Male specificity was
      demonstrated by gas chromatographic comparison of male and female volatile
      emissions and whole body extracts. Identifications were aided by coupled gas
      chromatographic-mass spectrometric (GC-MS) analysis, microchemical reactions,
      NMR, chiral GC analysis, and GC and MS comparison with authentic standards. Both
      the racemic and chiral forms of the gamma-lactone, as well as both E- and Z
      isomers were synthesized. Flight tunnel behavioral tests showed positive male and
      female S. agrili responses to both natural pheromone and synthetic blends, with
      upwind flight and landing on the source. Large field-cage tests, using yellow
      sticky traps baited with pheromone, captured approximately 50% of the released
      male and female wasps in 24-h periods. The use of pheromone-baited traps in the
      field could simplify the current detection method for determining parasitoid
      establishment (i.e., laboriously felling and peeling ash trees for recovery of S.
      agrili from infested EAB larvae).

PMID- 22456949
TI  - Pyrethrins protect pyrethrum leaves against attack by western flower thrips,
      Frankliniella occidentalis.
AB  - Pyrethrins are active ingredients extracted from pyrethrum flowers (Tanacetum
      cinerariifolium), and are the most widely used botanical insecticide. However,
      several thrips species are commonly found on pyrethrum flowers in the field, and
      are the dominant insects found inside the flowers. Up to 80% of western flower
      thrips (WFT, Frankliniella occidentalis) adults died within 3 days of initiating
      feeding on leaves of pyrethrum, leading us to evaluate the role of pyrethrins in
      the defense of pyrethrum leaves against WFT. The effects of pyrethrins on WFT
      survival, feeding behavior, and reproduction were measured both in vitro and in
      planta (infiltrated leaves). The lethal concentration value (LC50) for pyrethrins
      against WFT adults was 12.9 mg/ml, and pyrethrins at 0.1% (w/v) and 1% (w/v) had
      significantly negative effects on feeding, embryo development, and oviposition.
      About 20-70% of WFT were killed within 2 days when they were fed chrysanthemum
      leaves containing 0.01-1% pyrethrins. Chrysanthemum leaves containing 0.1% or 1%
      pyrethrins were significantly deterrent to WFT. In a no-choice assay, the
      reproduction of WFT was reduced significantly when the insects were fed leaves
      containing 0.1% pyrethrins, and no eggs were found in leaves containing 1%
      pyrethrins. Our results suggest that the natural concentrations of pyrethrins in
      the leaves may be responsible for the observed high mortality of WFT on
      pyrethrum.

PMID- 22456951
TI  - DEN+2-AAF-induced multistep hepatotumorigenesis in Wistar rats: supportive
      evidence and insights.
AB  - Diethylnitrosamine (DEN), found in many commonly consumed foods, has been
      reported to induce cancers in animals and humans. Several models have been
      developed to study multistage carcinogenesis in rat liver; these include the Solt
      Farber-resistant hepatocyte model. In the Solt-Farber model, the initiation
      consists of either a necrogenic dose of a hepatocarcinogen or a non-necrogenic
      dose in conjunction with partial hepatectomy (PH). We report a novel protocol for
      tumor induction in liver which eliminates the need for PH. Male Wistar rats were
      injected with single i.p. dose of DEN (200 mg/kg body weight), controls received
      saline only. After 1 week of recovery, the DEN-treated animals were administered
      with the repeated doses of 2-acetyamino fluorine (150 mg/kg body weight) orally
      in 1 % carboxymethyl cellulose that served as promoting agent. Thirty days after
      the DEN administration, hepatocellular damage was observed as evident by
      histopathological analysis. The marker enzyme analysis showed elevated levels of
      serum AST, ALT, and alkaline phosphatase and a decrease in the levels of liver
      superoxide dismutase and catalase. The oxidative stress in liver was confirmed by
      elevated levels of lipid peroxidation and a decrease in antioxidant parameters.

PMID- 22456950
TI  - Less is more: treatment with BTH and laminarin reduces herbivore-induced volatile
      emissions in maize but increases parasitoid attraction.
AB  - Chemical plant strengtheners find increasing use in agriculture to enhance
      resistance against pathogens. In an earlier study, it was found that treatment
      with one such resistance elicitor, BTH (benzo-(1, 2, 3)-thiadiazole-7-carbothioic
      acid S-methyl ester), increases the attractiveness of maize plants to a parasitic
      wasp. This surprising additional benefit of treating plants with BTH prompted us
      to conduct a series of olfactometer tests to find out if BTH and another
      commercially available plant strengthener, Laminarin, increase the attractiveness
      of maize to three important parasitic wasps, Cotesia marginventris, Campoletis
      sonorensis, and Microplitis rufiventris. In each case, plants that were sprayed
      with the plant strengtheners and subsequently induced to release volatiles by
      real or mimicked attack by Spodoptera littoralis caterpillars became more
      attractive to the parasitoids than water treated plants. The elicitors alone or
      in combination with plants that were not induced by herbivory were not attractive
      to the wasps. Interestingly, plants treated with the plant strengtheners did not
      show any consistent increase in volatile emissions. On the contrary, treated
      plants released less herbivore-induced volatiles, most notably indole, which has
      been reported to interfere with parasitoid attraction. The emission of the
      sesquiterpenes (E)-beta-caryophyllene, beta-bergamotene, and (E)-beta-farnesene
      was similarly reduced by the treatment. Expression profiles of marker genes
      showed that BTH and Laminarin induced several pathogenesis related (PR) genes.
      The results support the notion that, as yet undetectable and unidentified
      compounds, are of major importance for parasitoid attraction, and that these
      attractants may be masked by some of the major compounds in the volatile blends.
      This study confirms that elicitors of pathogen resistance are compatible with the
      biological control of insect pests and may even help to improve it.

PMID- 22456953
TI  - Stress-induced expression of the transcription factor RERJ1 is tightly regulated
      in response to jasmonic acid accumulation in rice.
AB  - The plant hormone jasmonic acid (JA) regulates various developmental processes
      and plant defence responses to environmental stresses. We previously reported
      that RERJ1, a JA-inducible transcription factor in rice, is up-regulated by
      exposure to wounding and drought stress. Here, we demonstrated that the
      expression of RERJ1 after wounding is regulated in a JA-dependent manner in rice,
      based on histochemical analysis of RERJ1 promoter-GUS transgenic plants. RERJ1
      expression was induced only at the region of injury after wounding, whereas
      expression was induced in the entire leaf after drought. According to JA
      measurements of stressed leaves, high accumulation of endogenous JA was only
      detected around the wound site in a rice leaves, whereas the drought treatment
      led to uniform accumulation of JA in the entire leaf, suggesting that RERJ1 will
      be a useful marker gene for studies on localization of JA in rice. Nuclear
      localization and transactivation ability of RERJ1 were also demonstrated. These
      results suggest that RERJ1 plays a role as a transcriptional activator for
      regulating stress-inducible gene expression, with a strong correlation to JA
      accumulation in the stressed region.

PMID- 22456955
TI  - Phosphino-carboxamides: the inconspicuous gems.
AB  - Compounds combining phosphine and carboxamide moieties in their molecules have
      developed virtually unnoticed into a specific class of highly structurally
      versatile and tuneable donor molecules finding manifold use in various fields,
      particularly in coordination chemistry, biomedical sciences and in catalysis. In
      the latter field, some phosphinoamides became the real privileged ligands and an
      indispensable part of a standard toolbox for synthetic chemists. This critical
      review aims to give an overview of the multifaceted chemistry of such compounds,
      paying attention to both the fundamentals and recent developments in this
      continuously expanding field.

PMID- 22456952
TI  - Pisum sativum wild-type and mutant stipules and those induced by an auxin
      transport inhibitor demonstrate the entire diversity of laminated stipules
      observed in angiosperms.
AB  - About a quarter of angiosperm species are stipulate. They produce stipule pairs
      at stem nodes in association with leaves. Stipule morphology is treated as a
      species-specific characteristic. Many species bear stipules as laminated organs
      in a variety of configurations, including laterally free large foliaceous, small,
      or wholly leaf-like stipules, and as fused intrapetiolar, opposite, ochreate or
      interpetiolar stipules. In Pisum sativum, the wild-type and stipule-reduced and
      cochleata mutants are known to form free large, small, and leaf-like stipules,
      respectively. Auxin controls initiation and development of plant organs and
      perturbations in its availability and distribution in the meristems, caused by
      auxin transport inhibitor(s) (ATIs), lead to aberrations in leaf development. The
      effect(s) of ATI(s) on stipule development are unexplored. To study the effect of
      the ATI 1-N-naphthylphthalamic acid (NPA) on stipule morphogenesis, P. sativum
      explants were grown in vitro in presence of a sublethal concentration of NPA. The
      NPA-treated shoots produced fused stipules of all the different types described
      in angiosperms. The observations indicate that (a) the gene sets for stipule
      differentiation may be common in angiosperms and (b) the interspecies stipule
      architectural differences are due to mutations, affecting gene expression or
      activity that got selected in the course of evolution.

PMID- 22456954
TI  - Immunological markers in allergic rhinitis patients treated with date palm
      immunotherapy.
AB  - OBJECTIVE: Allergic rhinitis (AR) is regulated by the local production and
      release of several cytokines. Allergen specific immunotherapy (IT) has been
      widely used for many years as a specific treatment of allergic diseases. This
      study aimed to investigate the changes in clinical and immunological markers
      before and after Phoenix dactylifera IT in AR patients. MATERIALS AND METHODS:
      Total symptom score and levels of total immunoglobulin E (IgE), albumin,
      interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-10,
      IL-4, and IL-13 were measured in the serum and nasal samples of thirty non-atopic
      healthy controls and thirty patients with allergic rhinitis before and after 15
      months of IT. RESULTS: We found significantly higher concentrations of serum TNF
      alpha and nasal TNF-alpha and IL-13, and significantly lower concentration of
      nasal IL-10, in allergic patients than in non-allergic. Moreover, serum and nasal
      IL-10 increased significantly after IT. However, there was neither a significant
      reduction in total IgE nor a significant increase in IFN-gamma at the end of IT.
      CONCLUSIONS: Our data show a clinical improvement associated with a decline in
      some inflammation parameters after IT. Moreover, date palm IT induced a
      significant increase in serum and nasal IL-10 levels.

PMID- 22456956
TI  - Naturalistic pharmacotherapy of acute episodes of schizophrenic disorders in
      comparison to treatment guidelines.
AB  - INTRODUCTION: This study was designed to investigate to what extent guidelines
      regarding the pharmacological treatment of patients suffering from schizophrenia
      like psychosis are adopted in a naturalistic treatment setting. METHODS: Medical
      records of n=819 patients undergoing inpatient treatment for schizophrenia-like
      psychosis in 11 psychiatric hospitals in northwestern Germany were
      retrospectively analyzed and findings were compared to current schizophrenia
      guideline recommendations. RESULTS: The prescription rate of second generation
      antipsychotics increased from 47.1% on admission to 62.5% at discharge. Only half
      the patients (52.3%) received antipsychotic monotherapy while 47.7% took between
      2 and 4 antipsychotic substances at a time. Dosage increases occurred most
      frequently (in 60%) within the first week of inpatient treatment, 16.6%
      experienced an elevation between days 15 and 29. A change within the atypical
      medication was found in 19.3%. Clozapine prescriptions increased throughout the
      treatment but were combined with other antipsychotic substances in the majority
      of cases. CONCLUSION: Under naturalistic conditions guideline recommendations for
      treatment of schizophrenia-like psychosis are adhered to only partially.
      Combination therapy with 2 or more antipsychotic drugs is quite common despite a
      clear recommendation for monotherapy.

PMID- 22456957
TI  - Orthology relations, symbolic ultrametrics, and cographs.
AB  - Orthology detection is an important problem in comparative and evolutionary
      genomics and, consequently, a variety of orthology detection methods have been
      devised in recent years. Although many of these methods are dependent on
      generating gene and/or species trees, it has been shown that orthology can be
      estimated at acceptable levels of accuracy without having to infer gene trees
      and/or reconciling gene trees with species trees. Thus, it is of interest to
      understand how much information about the gene tree, the species tree, and their
      reconciliation is already contained in the orthology relation on the underlying
      set of genes. Here we shall show that a result by Bocker and Dress concerning
      symbolic ultrametrics, and subsequent algorithmic results by Semple and Steel for
      processing these structures can throw a considerable amount of light on this
      problem. More specifically, building upon these authors' results, we present some
      new characterizations for symbolic ultrametrics and new algorithms for recovering
      the associated trees, with an emphasis on how these algorithms could be
      potentially extended to deal with arbitrary orthology relations. In so doing we
      shall also show that, somewhat surprisingly, symbolic ultrametrics are very
      closely related to cographs, graphs that do not contain an induced path on any
      subset of four vertices. We conclude with a discussion on how our results might
      be applied in practice to orthology detection.

PMID- 22456967
TI  - Correlative imaging of spontaneous coronary artery dissection.

PMID- 22456968
TI  - Advances in SPECT camera software and hardware: currently available and new on
      the horizon.

PMID- 22456969
TI  - Stress CT perfusion: coupling coronary anatomy with physiology.
AB  - While multiple different imaging tests can be used to evaluate patients with
      known or suspected coronary artery disease (CAD), each of them is designed to
      evaluate either coronary anatomy or physiology. Recently, it has been recognized
      that cardiac CT can be used to evaluate stress and rest myocardial perfusion in
      addition to its capabilities to image the coronary arteries, thus allowing for
      the simultaneous evaluation of the anatomical burden and physiological
      significance of CAD in a single exam. In this review, the strengths and the
      limitations of imaging coronary anatomy and myocardial perfusion will be
      discussed. Next, key technical aspects of how to perform and interpret CT
      perfusion imaging will be summarized while providing an update of the most recent
      data in this emerging field. Finally, future directions and opportunities for
      further research will be discussed.

PMID- 22456975
TI  - PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review
      estimating the chance of healthy offspring.
AB  - BACKGROUND: Mitochondrial disorders are often fatal multisystem disorders,
      partially caused by heteroplasmic mitochondrial DNA (mtDNA) point mutations.
      Prenatal diagnosis is generally not possible for these maternally inherited
      mutations because of extensive variation in mutation load among embryos and the
      inability to accurately predict the clinical expression. The aim of this study is
      to investigate if PGD could be a better alternative, by investigating the
      existence of a minimal mutation level below which the chance of an embryo being
      affected is acceptably low, irrespective of the mtDNA mutation. METHODS: We
      performed a systematic review of muscle mutation levels, evaluating 159 different
      heteroplasmic mtDNA point mutations derived from 327 unrelated patients or
      pedigrees, and reviewed three overrepresented mtDNA mutations (m.3243A>G,
      m.8344A>G and m.8993T>C/G) separately. RESULTS: Mutation levels were included for
      familial mtDNA point mutations only, covering all affected (n = 195) and
      unaffected maternal relatives (n = 19) from 137 pedigrees. Mean muscle mutation
      levels were comparable between probands and affected maternal relatives, and
      between affected individuals with tRNA- versus protein-coding mutations. Using an
      estimated a priori prevalence of being affected in pedigrees of 0.477, we
      calculated that a 95% or higher chance of being unaffected was associated with a
      muscle mutation level of 18% or less. At a mutation level of 18%, the predicted
      probability of being affected is 0.00744. The chance of being unaffected was
      lower only for the m.3243A>G mutation (P < 0.001). Most carriers of mtDNA
      mutations will have oocytes with mutation levels below this threshold.
      CONCLUSIONS: Our data show, for the first time, that carriers of heteroplasmic
      mtDNA mutations will have a fair chance of having healthy offspring, by applying
      PGD. Nevertheless, our conclusions are partly based on estimations and, as
      indicated, do not provide absolute certainty. Carriers of mtDNA should be
      informed about these constraints.

PMID- 22456977
TI  - Childhood and young adult-onset depression are associated with similar
      psychosocial risk factors.

PMID- 22456976
TI  - Analysis of the DNA damage produced by a platinum-acridine antitumor agent and
      its effects in NCI-H460 lung cancer cells.
AB  - High-performance liquid chromatography in conjunction with electrospray mass
      spectrometry (LC-ESMS) was used to structurally characterize the adducts formed
      by the platinum-acridine agent [PtCl(en)(N-(2-(acridin-9-ylamino)ethyl)-N
      methylpropionimidamide)](NO(3))(2) (compound 1) in cell-free DNA. Compound 1
      forms monofunctional adducts exclusively with guanine, based on the fragments
      identified in enzymatic digests (dG*, dGMP*, dApG*, and dTpG*, where the asterisk
      denotes bound drug). The time course of accumulation and DNA adduct formation of
      compound 1 and the clinical drug cisplatin in NCI-H460 lung cancer cells at
      physiologically relevant drug concentrations (0.1 MUM) was studied by inductively
      coupled plasma mass spectrometry (ICP-MS). Compound 1 accumulates rapidly in
      cells and reaches intracellular levels of up to 60-fold higher than those
      determined for cisplatin. The hybrid agent shows unusually high DNA binding
      levels: while cisplatin adducts form at a maximum frequency of 5 adducts per
      10(6) nucleotides, compound 1 produces 25 adducts per 10(6) nucleotides after
      only 3 h of continuous incubation with the lung cancer cells. The high overall
      levels of compound 1 in the cells and in cellular DNA over the entire 12-h
      treatment period translate into a rapid decrease in cell viability. Possible
      implications of these findings for the mechanism of action of compound 1 and the
      agent's potential to overcome tumor resistance to cisplatin are discussed.

PMID- 22456978
TI  - Is cultural activity at work related to mental health in employees?
AB  - OBJECTIVE: To examine relationships between work-based cultural activities and
      mental employee health in working Swedes. HYPOTHESIS: A positive relationship
      between frequent cultural activity at work and good employee health was expected.
      RESEARCH DESIGN: Random sample of working Swedish men and women in three waves,
      2006, 2008 and 2010, on average 60 % participation rate. METHODS: A postal
      questionnaire with questions about cultural activities organised for employees
      and about emotional exhaustion (Maslach) and depressive symptoms (short form of
      SCL). Employee assessments of "non-listening manager" and work environment
      ("psychological demands" and "decision latitude") as well as socioeconomic
      variables were covariates. Cross-sectional analyses for each study year as well
      as prospective analyses for 2006-2008 and 2008-2010 were performed. MAIN OUTCOME
      AND RESULTS: Lower frequency of cultural activities at work during the period of
      high unemployment. The effects of relationships with emotional exhaustion were
      more significant than those with depressive symptoms. The associations were
      attenuated when adjustments were made for manager function (does your manager
      listen?) and demand/control. Associations were more pronounced during the period
      with low unemployment and high cultural activity at work (2008). In a prospective
      analysis, cultural activity at work in 2008 had an independent statistically
      significant "protective" effect on emotional exhaustion in 2010. No corresponding
      such association was found between 2006 and 2008. CONCLUSIONS: Cultural
      activities at work vary according to business cycle and have a statistical
      association with mental employee health, particularly with emotional exhaustion.
      IMPLICATIONS FOR FUTURE RESEARCH: There are particularly pronounced statistical
      protective effects of frequent cultural activity at work on likelihood of
      emotional exhaustion among employees.

PMID- 22456979
TI  - Physical job demands and related health complaints among surgeons.
AB  - PURPOSE: Surgeons' poor physical health and high physical job demands might
      threaten good quality of care. We aimed to compare the prevalence of physical
      complaints of surgeons, their physical work ability and the physical job demands
      of surgeons with that of other hospital physicians. METHODS: All medical doctors
      (n = 958) of one academic medical center were invited to complete the online
      questionnaire to assess the physical work ability and the prevalence of regional
      musculoskeletal complaints. A purposive sample of 44 surgeons and 82 other
      hospital physicians were systematically observed during work to quantify the
      physical job demands for an average working day. RESULTS: More surgeons found
      their work to be physically strenuous (41 vs. 13 %, p < .000) and more were
      bothered by working in uncomfortable or exhausting postures (73 vs. 27 %, p <
      .001). Both groups reported that most of their physical complaints were in the
      neck (39 and 32 %) and arm regions (36 and 27 %). The majority of surgeons (86 %)
      and other hospital physicians (79 %) experienced difficulties coping with their
      job demands because of their physical state once a month or less. Compared with
      other hospital physicians, surgeons stand longer (4 vs. 3 h, p = .004) and
      perform fine repetitive movements longer (80 vs. 3 min, p < .001) during an
      average working day. CONCLUSIONS: Exposure to several physical job demands that
      are perceived as uncomfortable and exhausting and the presence of physical health
      complaints reduce surgeons' work functioning.

PMID- 22456981
TI  - Risk factors of portal vein thrombosis in Crohn's disease patients.
AB  - INTRODUCTION: Patients with inflammatory bowel disease, such as Crohn's disease
      (CD), suffer from a threefold increase in the risk of venous thromboembolism.
      Small bowel, segmental bowel, or ileocolonic resection to treat Crohn's disease
      can lead to rare complications of portal vein thrombosis (PVT), which can lead to
      further poor health outcomes, such as small bowel ischemia. The study attempts to
      find different risk factors that may be associated with postoperative
      complications of PVT in Crohn's disease patients. METHODS: In a 1 to 3 case
      control study following Institutional Review Board approval, 13 Crohn's disease
      patients with documented radiological postoperative diagnosis of PVT from 2004 to
      2011 and 39 CD patients who did not have postoperative PVT were matched by
      retrospective chart review for patient demographics, preoperative course and
      workup, anticoagulant use, and operative procedure. Univariate analysis was
      performed to draw correlations on risk factors for the development of PVT.
      RESULTS: In the 13 CD patients with PVT, concurrent cancer, liver disease, and
      dyslipidemia were present in 23.1%, 23.1%, and 15.4% of the population,
      respectively. Compared to the 39 CD only patients, concurrent cancer, liver
      disease, and dyslipidemia were present in only 2.6%, 2.6%, and 0% of the
      population, respectively. Of the CD patients with PVT, 61.5% were on preoperative
      steroids compared to 28.9% of the CD only patients. PVT development in CD
      patients is correlated with concurrent cancer (p = 0.016), liver disease (p =
      0.016), dyslipidemia (p = 0.012), and preoperative steroid usage (p = 0.036).
      CONCLUSIONS: Concurrent cancer, liver disease, dyslipidemia, and preoperative
      steroid usage were risk factors associated with the development of PVT in Crohn's
      patients. Since there is limited literature on PVT in CD, more data needs to be
      collected, and additional studies should be done to further assess the
      prevention, diagnosis, and management of the disease.

PMID- 22456982
TI  - Effect of reactivity on cellular accumulation and cytotoxicity of oxaliplatin
      analogues.
AB  - The purpose of this study was to systematically investigate the relationships
      between reactivity, cellular accumulation, and cytotoxicity of a panel of
      oxaliplatin analogues with different leaving groups in human carcinoma cells. The
      reactivity of the complexes towards the nucleotides 2'-deoxyguanosine 5'
      monophosphate and 2'-deoxyadenosine 5'-monophosphate was studied using capillary
      electrophoresis. Cellular accumulation and cytotoxicity were measured in an
      oxaliplatin-sensitive and oxaliplatin-resistant ileocecal colorectal
      adenocarcinoma cell line pair (HCT-8/HCT-8ox). Platinum concentrations were
      determined by flameless atomic absorption spectrometry. The 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to
      assess cytotoxicity. Early cellular platinum accumulation was predominantly
      affected by lipophilicity. A relationship between reactivity and cellular
      accumulation was observed for three of four platinum complexes investigated,
      whereas the most lipophilic oxaliplatin analogue was an exception. Increased
      reactivity and reduced lipophilicity were associated with high cytotoxic
      activity. Resistance was influenced by lipophilicity but not by reactivity. The
      observed relationships may help in the design of analogues with high antitumoral
      activity in oxaliplatin-sensitive as well as oxaliplatin-resistant cells.

PMID- 22456983
TI  - Breast cancer incidence trends in European women aged 20-39 years at diagnosis.
AB  - An increase in the incidence of breast cancer in women aged<40 years has been
      reported in recent years. Increased incidence could be partly explained by subtle
      detection biases, but the role of other risk factors cannot be ruled out. The
      purpose of the present study was to investigate the changes in temporal trends in
      breast cancer incidence in European women aged 20-39 years at diagnosis. Age
      specific breast cancer incidence rates for 17 European Cancer Registries were
      retrieved for the calendar period 1995-2006. Cancer registries data were pooled
      to reduce annual fluctuations present in single registries and increase incidence
      rates stability. Regression models were fitted to the data assuming that the
      number of cancer cases followed the Poisson distribution. Mean annual changes in
      the incidence rate (AIC) across the considered time window were calculated. The
      AIC estimated from all European registries was 1.032 (95% CI=1.019-1.045) and
      1.014 (95% CI=1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis,
      respectively. The major change was detected among women aged 25-29 years at
      diagnosis: AIC=1.033 (95% CI=1.020-1.046). The upward trend was not affected when
      registries with high or low AIC were removed from the analysis (sensitivity
      analysis). Our findings support the presence of an increase in the incidence of
      breast cancer in European women in their 20s and 30s during the decade 1995-2006.
      The interpretation of the observed increase is not straightforward since a number
      of factors may have affected our results. The estimated annual increase in breast
      cancer incidence may result in a burden of the disease that is important in terms
      of public health and deserves further investigation of possible risk factors.

PMID- 22456984
TI  - Mechanisms of estrogen-independent breast cancer growth driven by low estrogen
      concentrations are unique versus complete estrogen deprivation.
AB  - Despite the success of the aromatase inhibitors (AIs) in treating estrogen
      receptor positive breast cancer, 15-20 % of patients receiving adjuvant AIs will
      relapse within 5-10 years of treatment initiation. Long-term estrogen deprivation
      (LTED) of breast cancer cells in culture mimics AI-induced estrogen depletion to
      dissect mechanisms of AI resistance. However, we hypothesized that a subset of
      patients receiving AI therapy may maintain low circulating concentrations of
      estrogens that influence the development of endocrine resistance. We expanded
      established LTED models to account for incomplete suppression of estrogen
      synthesis during AI therapy. MCF-7 cells were grown in medium with charcoal
      stripped serum supplemented with defined concentrations of 17beta-estradiol (E2)
      or the estrogenic androgen metabolite 5alpha-androstane-3beta,17beta-diol
      (3betaAdiol), an endogenous selective estrogen receptor modulator. Cells were
      selected in concentrations of E2 or 3betaAdiol that induce 10 or 90 percent of
      maximal proliferation (EC(10) and EC(90), respectively), or estrogen deprived.
      Estrogen independence was evaluated during selection by assessing cell growth in
      the absence or presence of E2 or 3betaAdiol. Following >7 months of selection,
      estrogen independence developed in estrogen-deprived cells and EC(10)-selected
      cells. Functional analyses demonstrated that estrogen-deprived and EC(10)
      selected cells developed estrogen independence via unique mechanisms, ERalpha
      independent and dependent, respectively. Estrogen-independent proliferation in
      EC(10)-selected cells could be blocked by kinase inhibitors. However, these cells
      were resistant to kinase inhibition in the presence of low steroid
      concentrations. These data demonstrate that further understanding of the total
      estrogen environment in patients on AI therapy who experience recurrence is
      necessary to effectively treat endocrine-resistant disease.

PMID- 22456985
TI  - Measuring the impact of Hurricane Katrina on access to a personal healthcare
      provider: the use of the National Survey of Children's Health for an external
      comparison group.
AB  - This paper examined the effect of Hurricane Katrina on children's access to
      personal healthcare providers and evaluated the use of propensity score methods
      to compare a nationally representative sample of children, as a proxy for an
      unexposed group, with a smaller exposed sample. 2007 data from the Gulf Coast
      Child and Family Health (G-CAFH) Study, a longitudinal cohort of households
      displaced or greatly impacted by Hurricane Katrina, were matched with 2007
      National Survey of Children's Health (NSCH) data using propensity score
      techniques. Propensity scores were created using poverty level, household
      educational attainment, and race/ethnicity, with and without the addition of
      child age and gender. The outcome was defined as having a personal healthcare
      provider. Additional confounders (household structure, neighborhood safety,
      health and insurance status) were also examined. All covariates except gender
      differed significantly between the exposed (G-CAFH) and unexposed (NSCH) samples.
      Fewer G-CAFH children had a personal healthcare provider (65 %) compared to those
      from NSCH (90 %). Adjusting for all covariates, the propensity score analysis
      showed exposed children were 20 % less likely to have a personal healthcare
      provider compared to unexposed children in the US (OR = 0.80, 95 % CI 0.76,
      0.84), whereas the logistic regression analysis estimated a stronger effect (OR =
      0.28, 95 % CI 0.21, 0.39). Two years after Hurricane Katrina, children exposed to
      the storm had significantly lower odds of having a personal health care provider
      compared to unexposed children. Propensity score matching techniques may be
      useful for combining separate data samples when no clear unexposed group exists.

PMID- 22456986
TI  - Oral health need and access to dental services: evidence from the National Survey
      of Children's Health, 2007.
AB  - This study examines associations between parents' report of their children's oral
      health and receipt of a dental visit for preventive care. We conducted a cross
      sectional analysis of oral health status and receipt of a preventive dental visit
      among US children and youth, ages 1-17 years, using data from the 2007 National
      Survey of Children's Health (n = 86,764). Survey-weighted logistic regression was
      used to estimate associations between perceived oral health status and receipt of
      a preventive dental health visit in the prior 12 months. Overall, 78 % of
      children and youth received at least one preventive dental health visit in the
      prior year. Among the youngest children, lower oral health status was associated
      with higher odds of receiving a preventive dental visit; among older children,
      lower oral health status was associated with lower odds of receiving a dental
      visit for preventive care. Use of preventive dental health care is below national
      target goals. Younger children in worse oral health are more likely, and older
      youth less likely, to receive preventive dental care. Public health efforts to
      educate parents to seek early and ongoing preventive oral health care, rather
      than services in response to problems, may yield oral health benefits later in
      childhood and over the life course.

PMID- 22456987
TI  - The impact of tobacco control policies on disparities in children's secondhand
      smoke exposure: a comparison of methods.
AB  - To examine the impact of cigarette excise taxes and smoke-free legislation on
      tobacco use among households with school-age children and adolescents as well as
      disparities in children's secondhand smoke exposure. We compare the results from
      models using causal inference techniques to those from cross-sectional models. We
      linked families of 6-17-year-olds from the 2003 (N = 67,607) and 2007 (N =
      62,768) contacts of the National Survey of Children's Health with state-level
      cigarette excise taxes and smoke-free legislation total score (0 [none]-32 [very
      strong]) in 2001 and 2005. Parents reported whether anyone in the household used
      tobacco products. In adjusted causal inference models every $1.00 increase in
      cigarette excise tax between 2001 and 2005 was associated with a 4 percentage
      point decrease in household tobacco use between 2003 and 2007 (p = 0.008);
      however, there was no effect of smoke-free legislation on household tobacco use.
      Significant interactions revealed that cigarette tax increases were only
      associated with reductions in household tobacco use for parents of white children
      and, separately, lower income households. In contrast, in adjusted cross
      sectional models, a higher smoke-free legislation total score was associated with
      a lower prevalence of household tobacco use. Stronger cigarette excise taxes
      decrease tobacco use among households with school-age children and adolescents,
      but smoke-free legislation at the state level does not change parental smoking.
      Since cross-sectional models cannot assess the direction of causality,
      evaluations should employ causal inference methods to help inform policy
      decisions to reduce disparities in adult smoking and, ultimately, protect
      children from secondhand smoke.

PMID- 22456989
TI  - Radioactivity concentrations in soil and dose assessment for Samsun city centre,
      Turkey.
AB  - In this study, natural gamma radioactivity levels were determined in the soil
      samples of the Samsun city centre by using the gamma ray spectrometry method. The
      analysis carried out with the high-purity germanium gamma spectrometry system has
      shown that average activity concentrations of (238)U, (232)Th, (40)K and (137)Cs
      were 19+/-2, 22+/-4, 521+/-23 and 15+/-1 Bq kg(-1), respectively. From the gamma
      analysis of soil samples, the average value of the absorbed gamma dose rates in
      air and the average value of the external annual effective dose rates were
      calculated as 45+/-4 nGy h(-1) and 55+/-5 uSv y(-1), respectively. The external
      hazard index has also been calculated and it has been found that the radiation
      hazard in Samsun is insignificant.

PMID- 22456990
TI  - Assessment of paediatric CT exposure in a Portuguese hospital.
AB  - In this study, the characterisation of radiation exposure of paediatric patients
      in computerised tomography (CT) procedures was performed for a Portuguese
      hospital. Dosimetric data and technical parameters used for CT examinations were
      retrieved, compiled and analysed over a period of 1 y. Five paediatric age groups
      were considered, covering the age interval from 0 (newborn) to 18 y old and, for
      each age group, the relative frequency of the most frequent CT examinations
      (head, ears, sinuses, chest and abdomen examinations) is analysed. The exposure
      settings used (kilovolt and milliampire) were compared with the values
      established in the local (hospital) clinical protocols for consistency analysis.
      Average CT dose index(vol) and dose length product values, per age group, are
      presented as well as the corresponding estimated mean effective dose values.
      Results showed an evident need for a protocol review, in order to adjust
      practices to international guidelines for performing optimised paediatric CT
      examinations. Also, an increased awareness of staff to Radiological Protection
      principles in CT in particular, these of utmost importance, seems necessary.

PMID- 22456988
TI  - Antithrombotic therapy in patients with acute coronary syndrome and diabetes
      mellitus.
AB  - Acute coronary syndrome (ACS) is associated with high mortality even in the acute
      phase as well as in the post-acute (chronic) phase. Diabetes mellitus type 2 (DM
      2), on the other hand, further increases mortality after ACS. Several new
      antiplatelet and antithrombotic drugs available for clinical use have also been
      investigated in patients with DM-2, and the guidelines of the European Society of
      Cardiology (ESC) were recently adapted. However, in daily clinical practice
      choosing the most suitable regimen is a challenge in many cases. This review
      article aims to shed light on and simplify antiplatelet and antithrombotic
      therapy in ACS patients with DM-2 in order to ease the clinician's decision
      making.

PMID- 22456991
TI  - Measurement procedure to assess exposure to extremely low-frequency fields: a
      primary school case study.
AB  - How to correctly measure the exposure of general public to extremely low
      frequency (ELF) radiation is a key issue for ELF epidemiological studies. This
      paper proposes a measurement procedure to accurately assess the exposure of
      people to electric and magnetic field in the frequency band from 5 Hz to 100 kHz
      in buildings and their premises. As ELF radiation could be particularly harmful
      to children, the measurement procedure is focused on exposure to ELF in schools.
      Thus, the students' exposure to ELF fields can be assessed by correlating the ELF
      measurements to the hours of school activity. In this paper, the measurement
      protocol was applied to study the ELF exposure on students from Garcia Quintana
      primary school in Valladolid, Spain. The campaign of measurements for ELF
      exposure assessment in this primary school was of great interest for the Regional
      Council of Public Health because of the social alarm generated by the presence of
      a significant number cancer cases in children.

PMID- 22456996
TI  - Angiotensin-(1-7) suppresses the number and function of the circulating
      fibrocytes by upregulating endothelial nitric oxide synthase expression.
AB  - There is growing evidence suggesting that circulating fibrocytes (CFs) play a
      pivotal role in tissue repair and fibrosis. In contrast, in recent studies,
      angiotensin-(1-7) [Ang-(1-7)] has been shown to antagonize fibrosis. The purpose
      of this study was to examine the direct effect of Ang-(1-7) on CFs. Total
      mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density
      gradient centrifugation. Using laser scanning confocal microscopy, CFs were
      identified as adherent cells that stained positive for both CD34 and collagen-I.
      After 14 days of culture, CFs were stimulated with Ang-(1-7) at concentrations of
      10 nM, 100 nM, 1 MUM or 10 MUM, in the absence and presence of pretreatment with
      A-779, N(G)-nitro-L-arginine methyl ester (L-NAME) or both, for 24, 48 or 72 h.
      The number of cells, cellular proliferation, and level of apoptosis were
      determined by hematoxylin and eosin staining, the Cell Counting Kit-8 (CCK8)
      assay and the annexin V/propidium iodide binding assay, respectively. The
      collagen content of CFs was measured by the concentration of hydroxyproline,
      which was detected using the enzymatic digestion method. The expression of
      endothelial nitric oxide synthase (eNOS) was assayed by western Blot analysis,
      while nitric oxide (NO) generation was detected using the Griess method. We found
      that Ang-(1-7) increases apoptosis and eNOS/NO production in CFs. In addition,
      Ang-(1-7) decreases the number, proliferative capacity and collagen-secretion of
      CFs in a concentration- and time-dependent manner. These data suggest that Ang-(1
      7) suppresses the both the number and function of CFs possibly by increasing
      eNOS/NO production in the CFs.

PMID- 22456997
TI  - Carboxy terminus of heat shock protein (HSP) 70-interacting protein (CHIP)
      inhibits HSP70 in the heart.
AB  - Heat shock protein (HSP) 70 plays a critical role in protecting the heart from
      various stressor-induced cell injuries; the mechanism remains to be further
      understood. The present study aims to elucidate the effect of a probiotics
      derived protein, LGG-derived protein p75 (LGP), in alleviating the
      ischemia/reperfusion (I/R)-induced heart injury. We treated rats with the I/R
      with or without preadministration with LGP. The levels of HSP70 and carboxy
      terminus of HSP70-interacting protein (CHIP) in the heart tissue were assessed by
      enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of
      CHIP on suppression of HSP70 and the effect of LGP on suppression of CHIP were
      investigated with an I/R rat model and a cell culture model. The results showed
      that I/R-induced infarction in the heart could be alleviated by pretreatment with
      LGP. HSP70 was detected in naive rat heart tissue extracts. I/R treatment
      significantly suppressed the level of HSP70 and increased the levels of CHIP in
      the heart. A complex of CHIP/HSP70 was detected in heart tissue extracts. The
      addition of recombinant CHIP to culture inhibited HSP70 in heart cells. LGP was
      bound CHIP in heart cells and prevented the CHIP from binding HSP70. In summary,
      I/R can suppress HSP70 and increase CHIP in heart cells. CHIP can suppress HSP70
      that can be prevented by pretreatment with LGP. The results imply that CHIP may
      be a potential target in the prevention of I/R-induced heart cell injury.

PMID- 22456998
TI  - The interdependence of the reactive species of oxygen, nitrogen, and carbon.
AB  - This mini-review tries to summarize the main interdependences between the free
      radicals of oxygen, nitrogen, and carbon. Also, the main metabolic pathways for
      these radical species are described, as well as how these affect their
      interaction and functional implications. Emphasis is made on the metabolic
      disturbances induced by stressing aggressions that produce radical species. In
      this way, cellular oxidative imbalances created by the superiority of reactive
      oxygen species over the antioxidant systems produce both activation of nitroxide
      synthases and the oxidation of terminal nitrogen from L-arginine, as well as the
      metabolization of heme until carbon monoxide by nitric oxide-activated
      hemoxygenase. Also, multiple cellular protein and nucleoprotein alterations
      determined by these three kinds of radical species are completed by the
      involvement of hydrogen sulfide, which results from the degradation of L-cysteine
      by cistationine-gamma-lyase. In this way, sufficient experimental data tend to
      demonstrate the involvement of hydrogen sulfide and other thiol derivatives in
      the interrelations between oxygen, nitrogen, and carbon, which results in a true
      radical cascade. Thus, oxidative stress, together with nitrosative and carbonilic
      stress, may constitute a central point where other factors of vulnerability meet,
      and their interactions could have an important impact in many modern diseases.
      Considering that the actions of reactive species can be most of the time
      corrected, future studies need to establish the therapeutical importance of
      various agents which modulate oxidative, nitrosative, or carbonilic stress.

PMID- 22456999
TI  - Family history of malignant and benign thyroid diseases and risk of thyroid
      cancer: a population-based case-control study in New Caledonia.
AB  - PURPOSE: Exceptionally high incidence rates of thyroid cancer have been observed
      in New Caledonia, particularly in Melanesian women, but familial aggregation of
      thyroid diseases in this population is unknown. We study the association between
      family history of malignant or benign thyroid diseases and non-medullary thyroid
      cancer in this country. METHODS: We conducted a population-based case-control
      study including 332 cases with papillary or follicular carcinoma diagnosed in
      1993-1999 and 412 controls, matched by sex and 5-year age-group. RESULTS: Thyroid
      cancer was associated with a history of thyroid cancer in first-degree relatives
      (odds ratio (OR), 3.2; 95 % CI, 1.6-6.2) and with a family history of
      multinodular goiter (OR, 3.6; 95 % CI, 1.9-7.0). The ORs did not change by age at
      diagnosis and with the number of affected relatives. The study provides evidence
      that the familial component of thyroid cancer is particularly strong in men.
      Thyroid cancer was not associated with a family history of thyroid diseases in
      Melanesians from the Loyalty Islands, the area with the highest incidence rates
      for thyroid cancer, possibly indicating a high frequency of genetic
      susceptibility variants and lack of genetic variation in this population
      subgroup. CONCLUSION: Overall our findings confirm an elevated risk of thyroid
      cancer in individuals with a family history of malignant or benign thyroid
      diseases, particularly in Melanesians where familial aggregation of thyroid
      cancer had never been investigated before. The study of genetic variants in
      candidate susceptibility genes for thyroid cancer may help clarifying the absence
      of an association in the subgroup of Melanesians from the Loyalty Islands.

PMID- 22457000
TI  - Coffee, tea, soda, and caffeine intake in relation to risk of adult glioma in the
      NIH-AARP Diet and Health Study.
AB  - PURPOSE: We utilized the large, prospective NIH-AARP Diet and Health Study to
      further explore the hypothesis, suggested by two recent prospective cohort
      studies, that increased intake of coffee, tea, soda, and/or caffeine is
      associated with reduced adult glioma risk. METHODS: At baseline in 1995-1996,
      dietary intake, including coffee, tea, and soda, was assessed with a food
      frequency questionnaire. We used Cox proportional hazards models to calculate
      adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for glioma risk in
      relation to beverage intake. RESULTS: During follow-up of 545,771 participants
      through 2006, 904 participants were diagnosed with glioma. We found no trends of
      decreasing glioma risk with increasing intake of specific beverages or total
      caffeine. HR patterns for consumption of the caffeinated versus decaffeinated
      form of each beverage were inconsistent with a specific caffeine effect. HR
      patterns of reduced glioma risk for most categories of beverage intake greater
      than "none" prompted a post hoc analysis that revealed borderline-significant
      inverse associations for any versus no intake of tea (HR = 0.84; 95 % CI, 0.69
      1.03), total coffee plus tea (HR = 0.70; 95 % CI, 0.48-1.03), and soda (HR =
      0.82; 95 % CI, 0.67-1.01). CONCLUSIONS: The borderline-significant inverse
      associations could be explained by a threshold effect in which any beverage
      intake above a low level confers a beneficial effect, most likely due to beverage
      constituents other than caffeine. They could also be explained by non-drinkers of
      these beverages sharing unknown extraneous characteristics associated with
      increased glioma risk, or by chance.

PMID- 22457004
TI  - Association of MMP-3 (-1612 5A/6A) polymorphism with knee osteoarthritis in Thai
      population.
AB  - Osteoarthritis (OA) is a degenerative joint disorder resulting in destruction of
      articular cartilage, osteophyte formation, and subchondral bone sclerosis. In
      recent years, numerous genetic factors have been identified and implicated in
      causing osteoarthritis. One such genetic defect is a single nucleotide
      polymorphism at position -1612 of matrix metalloproteinase-3 (MMP-3) promoter
      region, known to lead to three possible genotypes, 5A/5A, 6A/6A, and 5A/6A. The
      purpose of this study was to investigate the association of MMP-3 -1612 5A/6A
      gene polymorphism with knee osteoarthritis in Thai population. Genotype
      distributions and allelic frequencies of MMP-3 -1612 5A/6A polymorphism were
      investigated in 200 participants (100 patients with knee osteoarthritis and 100
      healthy controls). Genotyping was performed using polymerase chain reaction
      restriction fragment length polymorphism. There was no statistically significant
      difference between the groups with respect to genotype distribution (P > 0.05).
      The 5A allele frequency was indicated as 15.5 %, and 6A allele was as 84.5 % in
      OA patients, whereas it was 10-90 % in the control group. Accordingly, the
      present study has indicated that the -1612 5A/6A polymorphism genotypes of MMP-3
      gene promoter do not play a role in the development of osteoarthritis in the Thai
      population.

PMID- 22457005
TI  - TLR3-mediated apoptosis and activation of phosphorylated Akt in the salivary
      gland epithelial cells of primary Sjogren's syndrome patients.
AB  - This study aimed at ascertain whether innate immunity is involved in the
      apoptosis of primary cultured salivary gland epithelial cells (SGECs) in primary
      Sjogren's syndrome (pSS). Induction of apoptosis of SGECs was performed using a
      TLR3 ligand, poly (I:C). Activation of phosphorylated-Akt (pAkt) and cleaved
      caspase 3 was determined by Western blotting or immunofluorescence. Expression of
      TLR2 and TLR3 with pAkt was observed in cultured SGECs after 24-h stimulation
      with each ligand. Compared with stimulation with the peptidoglycan or
      lipopolysaccharide, that with poly (I:C) induced significant nuclear
      fragmentation, as determined by Hoechst staining (p = 0.0098). Apoptosis was
      confirmed by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling
      (TUNEL) staining of SGECs from pSS patients and a normal subject. A significant
      increase in TUNEL-positive cells was observed by the addition of a PI3K
      inhibitor, LY294002. Poly (I:C) phosphorylated stress-activated protein
      kinase/Jun-terminal kinase and p44/42 MAP kinase as well as Akt. Furthermore,
      poly (I:C)-induced caspase 3 cleavage in SGECs was also inhibited by LY294002.
      Similar results were obtained using SGECs obtained from a normal subject. The
      results demonstrated for the first time that TLR3 induces the apoptotic cell
      death of SGECs via the PI3K-Akt signaling pathway.

PMID- 22457006
TI  - Swollen knee due to primary synovial chondromatosis in pediatrics: a rare and
      possibly misdiagnosed condition.

PMID- 22457007
TI  - Baseline anti-citrullinated peptide antibody (ACPA) titers and serum interleukin
      6 (IL-6) levels possibly predict progression of bone destruction in early stages
      of rheumatoid arthritis (ERA).
AB  - A prospective study was made to seek for a convenient biomarker to predict
      progression of bone destruction (PBD) in early stages of rheumatoid arthritis
      (ERA). All participated patients had definite RA and their radiographic stages
      were mild less than stage II of the Steinbrocker classification, naive for
      treatment of any DMARDs or corticosteroids. After the entry, they were treated
      according to the 2002 ACR management guideline for RA. The candidate biomarkers
      (RF-IgM, RF-IgG, CARF, ACPA, CRP, ESR, NTx, MMP-3, IL-6 and osteopontin) were
      measured at the entry. PBD was assessed radiographically by interval changes in
      the modified Sharp scores (DeltaSHS) for 24 months. The associations between
      DeltaSHS and baseline biomarkers were assessed statistically by multivariate
      regression analyses. Both the baseline ACPA and IL-6 levels correlated with PBD,
      suggesting that they could predict PBD in ERA.

PMID- 22457008
TI  - Reversal of multidrug resistance of KBV200 cells by triterpenoids isolated from
      Poria cocos.
AB  - Multidrug resistance (MDR) of tumor cells is one of the major problems
      encountered during cancer chemotherapy. In this paper, we isolated eight
      triterpenoids from Poria cocos and evaluated their effects on reversing MDR of
      KBV200 cells. Eight triterpenoids increase significantly vincristine-induced
      cytotoxicity in drug-resistant KBV200 cells at the concentrations of 12.5 ug/mL
      and 25 ug/mL. Dehydrotumulosic acid showed the best reversal effect: it increased
      KBV200 apoptosis induced by vincristine and inhibited P-gp function through
      enhancing the accumulation and retention of fluorescent P-gp substrate rhodamine
      123 in KBV200 cells but had no effect on P-gp expression.

PMID- 22457009
TI  - Clinical consequences of levator trauma.

PMID- 22457010
TI  - Comparing reliability between different ultrasound techniques.

PMID- 22457012
TI  - Energetics and mechanics of running men: the influence of body mass.
AB  - We investigated the relationship between mechanical and energy cost of transport
      and body mass in running humans. Ten severely obese (body mass ranging from 108.5
      to 172.0 kg) and 15 normal-weighted (52.0-89.0 kg) boys and men, aged 16.0-45.8
      years, participated in this study. The rate of O(2) consumption was measured and
      the subjects were filmed with four cameras for kinematic analysis, while running
      on a treadmill at 8 km h(-1). Mass specific energy cost (C (r)) and external
      mechanical work (W (ext)) per unit distance were calculated and expressed in
      joules per kilogram per meter, efficiency (eta) was then calculated as W (ext) *
      C (r) (-1) * 100. Both mass-specific C (r) and W (ext) were found to be
      independent of body mass (M) (C (r) = 0.002 M + 3.729, n = 25, R (2) = 0.05; W
      (ext) = -0.001 M + 1.963, n = 25, R (2) = 0.01). It necessarily follows that the
      efficiency is also independent of M (eta = -0.062 M + 53.3298, n = 25, R (2) =
      0.05). The results strongly suggest that the elastic tissues of obese subjects
      can adapt (e.g., thickening) to the increased mass of the body thus maintaining
      their ability to store elastic energy, at least at 8 km h(-1) speed, at the same
      level as the normal-weighted subjects.

PMID- 22457013
TI  - Patient turnover and the relationship between nurse staffing and patient
      outcomes.
AB  - High patient turnover (patient throughput generated by admissions, discharges,
      and transfers) contributes to increased demands and resources for care. We
      examined how the relationship between registered nurse (RN) staffing and failure
      to-rescue (FTR) varied with patient turnover levels by analyzing quarterly data
      from the University HealthSystem Consortium. The data included 42 hospitals,
      representing 759 nursing units and about 1 million inpatients. Higher RN staffing
      was associated with lower FTR. When patient turnover increased from 48.6% to
      60.7% on nonintensive units (non-ICUs), the beneficial effect of non-ICU RN
      staffing on FTR was reduced by 11.5%. RN staffing should be adjusted according to
      patient turnover because turnover increases patient care demand beyond that
      presented by patient count, and outcomes may be adversely affected.

PMID- 22457014
TI  - Salbutamol but not ipratropium abolishes leukotriene D4-induced gas exchange
      abnormalities in asthma.
AB  - PURPOSE: Leukotriene D(4) (LTD(4)) is a central mediator in asthma inducing
      bronchoconstriction and profound disturbances in pulmonary gas exchange in
      asthmatic subjects. The aim of the study was to compare, for the first time, the
      influence of the bronchodilators salbutamol (400 MUg) and ipratropium (80 MUg) on
      lung function changes induced by inhaled LTD(4). METHODS: Treatments were
      evaluated in a randomized, three-period, double-blind, placebo-controlled, cross
      over study where spirometric and pulmonary gas exchange indices were followed in
      12 subjects with mild asthma before and after LTD(4) challenge. RESULTS: Compared
      with placebo, salbutamol provided significant protection against the fall in
      FEV(1) (forced expiratory volume in 1 s) after LTD(4) challenge. Salbutamol also
      abolished the LTD(4)-induced gas exchange disturbances [decreased arterial oxygen
      tension (PaO(2)) and increased alveolar-arterial oxygen tension difference
      (AaPO(2))]. Ipratropium provided significant but less marked attenuation of the
      changes in FEV(1) and arterial oxygenation induced by LTD(4). CONCLUSION: Despite
      the equal bronchodilatory effects of salbutamol and ipratropium before the
      challenge with LTD(4), salbutamol was superior to ipratropium in preventing
      spirometric and gas exchange abnormalities. This result indicates a broader
      action of salbutamol on several of the disturbances that contribute to airway
      obstruction including, for example, exudation of plasma in the airway mucosa. The
      clinical implication of this new finding is that in this model of acute asthmatic
      airway obstruction, salbutamol was more effective than ipratropium.

PMID- 22457015
TI  - Pharmacokinetics, pharmacodynamics, and safety of clevidipine after prolonged
      continuous infusion in subjects with mild to moderate essential hypertension.
AB  - PURPOSE: Clevidipine is a rapidly-acting intravenous dihydropyridine
      antihypertensive acting via calcium channel blockade. This was a randomized,
      single-blind, parallel-design study of a 72-h continuous clevidipine infusion.
      METHOD: Doses of 2, 4, 8, or 16.0 mg/h or placebo were evaluated in 61 subjects
      with mild to moderate essential hypertension. IV clevidipine or placebo was
      initiated at 2.0 mg/h and force-titrated in doubling increments every 3 min to
      target dose, then maintained for 72 h. Blood pressure and heart rate were
      measured during infusion, and for 4, 6 and 8 h after termination of infusion,
      although oral therapy could be restarted at 4 h. Clevidipine blood levels were
      obtained during infusion and for 1 hour after termination. RESULTS: Rapid onset
      of drug effect occurred at all clevidipine dose levels, with consistent
      pharmacokinetics and rapid offset after 72-h infusion. No evidence of tolerance
      to the clevidipine drug effect was observed at any dose level over the 72-h
      infusion. No evidence of rebound hypertension was found for either 4 or 6 h after
      termination of the clevidipine infusion. At 8 h following cessation of
      clevidipine, blood pressure was not significantly higher than at baseline.
      Placebo-treated subjects had blood pressures lower than baseline at 8 h following
      infusion termination; hence, placebo-adjusted blood pressures tended to be
      slightly higher than baseline. CONCLUSION: This study supports the use of up to
      72 h of IV clevidipine therapy for the management of blood pressure, with
      consistent pharmacokinetic/pharmacodynamic characteristics and context
      insensitive half-life across the dose ranges evaluated.

PMID- 22457016
TI  - Systems genetic analysis of the effects of iron deficiency in mouse brain.
AB  - Iron regulation in the brain is both necessary and highly complex. Too little or
      too much iron can compromise neurological function, yet we still do not know all
      of the regulatory processes. In our research, we seek to identify genes and gene
      networks underlying individual differences in brain iron regulation. To this end,
      we fed mice from 20+ inbred strains a diet low in iron from weaning to 4 months
      of age. At sacrifice, we measured iron content in the ventral midbrain (VMB). The
      VMB contains the substantia nigra, a region particularly vulnerable to iron
      imbalance. The results showed high, inter-strain variability in dietary iron
      reduction, from almost no loss to more than 40 % vs. control. When we performed
      quantitative trait loci (QTL) analysis, we observed a significant area on
      chromosome 2. Within this QTL, we selected glial high-affinity glutamate
      transporter 1 (Glt1) as the leading candidate. Expression of this gene is both
      correlated with VMB iron and is also cis-modulated by local sequence variants
      that segregate in the BXD family. VMB expression differences of Glt1 in six
      strains covary with differential susceptibility to VMB iron loss.

PMID- 22457017
TI  - Regulation of estrogen receptor alpha gene expression in the mouse prefrontal
      cortex during early postnatal development.
AB  - Estrogens have many functions in the developing rodent brain, and most of these
      depend on the presence of estrogen receptors. Understanding how expression of
      these receptors are regulated is crucial for understanding the roles of estradiol
      in the male and female brain during development In rodents, the prefrontal cortex
      (PFC) has been shown to be involved in working memory, attention, and behavioral
      inhibition. Many studies have demonstrated an effect of estradiol on sex
      difference in these functions attributed to differences in the PFC. We have
      previously demonstrated that estrogen receptor alpha (ERalpha) expression
      decreases in the isocortex across early postnatal development. This decrease
      corresponds with an increase in methylation of many sites along the ERalpha
      promoter. Here we have examined both ERalpha and ERbeta mRNA expression in the
      PFC to determine if methylation also plays a role in this important brain region.
      We investigated expression of alternate promoters for ERalpha and methylation of
      CpG sites along two of these promoters. We found that the pattern of ERalpha mRNA
      expression in PFC was similar to the pattern of ERalpha expression in the
      isocortex and that there were no sex differences in the level of expression
      across development. We did, however, find subtle differences in promoter
      expression and methylation that may indicate a sex-specific difference in PFC
      during development resulting in a difference in adult response.

PMID- 22457018
TI  - [Current requirements for image management in radiotherapy].
AB  - AIMS AND METHODS: Treatment techniques of increasing complexity such as
      dynamic/rotational techniques mandate digital management and increasingly image
      guidance. This constantly increases requirements for image management and
      archiving. This article discusses the current status of these requirements and
      will present potential image administration strategies. RESULTS: Fundamentals of
      image administration and storage/archiving are presented (DICOM Standard,
      radiotherapy-specific issues) along the typical patient pathway (demographic
      data, radiotherapy treatment planning, signatures/approval of plan and image
      data, archiving of plan and image data). Different strategies for image
      management are presented (archiving centered on individual application vs.
      integral approach with central archiving in a DICOM-RT-PACS governed by a
      radiation oncology information system (ROCIS)). Infrastructural requirements
      depending on the amount of image data generated in the department are discussed.
      CONCLUSION: Application-centered image management provides access to image data
      including all relevant RT-specific elements. This approach, however, is not
      migration-safe, requires significant administrative work to ensure a redundancy
      level that protects against data loss and does not provide datasets that are
      linked to respective therapeutic interventions. Therefore, centralized image
      management and archiving that links images to patients and individual steps in
      the treatment pathway within a standardized DICOM(-RT) environment is preferable
      despite occasional problems with visualization of specific data elements.

PMID- 22457020
TI  - [HIV/AIDS care and international migrations in the rural district of Nanoro,
      Burkina Faso].
AB  - West African Countries account for almost half of the estimated 20 000 000
      international migrants in the continent. In the frame of the scaling up of HAART,
      our study aims to identify specific features and constraints of access to care
      for HIV migrant patients returning to Burkina Faso. From January 2007 to August
      2011, the Nanoro District Hospital, serving a rural area in the Centre-West of
      Burkina Faso, followed 437 HIV/AIDS adult patients. Migrants were 139/437 (31.8
      %), of whom 108/139 (77.7 %), declared they returned to Burkina Faso to seek
      care, because the area they migrated to did not offer specific HIV health
      assistance. At baseline, 113/139 (81,3 %) migrants and 181/298 (60,7 %) residents
      were in WHO clinical stages III or IV (p< 0.01). For every 100 patients/ year
      under HAART, 25.5 migrants (91.4 % of whom to foreign countries) and 5.7 Burkina
      residents were transferred to other centers (p<0.01). 21.8 migrants and 8.5
      residents were dead or lost to follow up (p<0.05). For migrant patients, access
      to HIV screening and care seems to be delayed. The high frequency of migrants
      under HAART working abroad requires an improved cooperation among the health
      systems of the African Countries.

PMID- 22457021
TI  - Effects of chronic cadmium poisoning on Zn, Cu, Fe, Ca, and metallothionein in
      liver and kidney of rats.
AB  - An experiment was conducted to invest effects of chronic cadmium poisoning on Zn,
      Cu, Fe, Ca, and metallothionein gene expression and protein synthesis in liver
      and kidney in rats. Forty rats, 6 weeks old, were randomly allocated into two
      groups. A group was given CdCl(2) (1 mg/KgCd(2+)) by intraperitoneal injection
      once a day. The other group was treated with normal saline in the same way. Liver
      and kidney were collected for analysis at the end of the third week. Results
      showed that Cd exposure increased Cd (P<0.01) and Zn (P<0.01) content both in
      liver and kidney. Fe and Ca concentration had a considerable increase in kidney
      (P<0.01), while both had different degree reduction in liver. Discrepancies
      between MT mRNA and protein were observed in liver and kidney. In liver, both MT
      mRNA and protein had a significant increase (P<0.01), while in kidney, only MT
      gene increase was checked. Meanwhile, the expression levels of MT-1 mRNA and MT-2
      mRNA were distinct between liver and kidney. The present study indicated that
      changes in tissue Cd and Zn levels tended to reflect MT mRNA expression, but bear
      no clear relationship with MT protein. There did not have a strict dose-dependent
      relationship among Cd content, MT gene expression, and MT protein synthesis. What
      is more, changes of Zn, Fe, Cu, and Ca had a certain interaction with both MT
      mRNA and protein.

PMID- 22457028
TI  - Next-generation sequencing demands next-generation phenotyping.
AB  - Next-generation sequencing (NGS) is the most powerful diagnostic tool since the
      roentgenogram. NGS will facilitate diagnosis on a massive scale, allowing
      interrogation of all genes in a single assay. It has been suggested that NGS will
      decrease the need for phenotyping in general and medical geneticists in
      particular. We argue that NGS will shift focus and approach of phenotyping. We
      predict that NGS performed for diagnostic purposes will yield variants in several
      genes, and consequences of these variants will need to be analyzed and integrated
      with clinical findings to make a diagnosis. Diagnostic skills of medical
      specialists will shift from a pre-NGS-test differential diagnostic mode to a post
      NGS-test diagnostic assessment mode. In research phenotyping and medical genetic
      assessments will remain essential as well. NGS can identify primary causative
      variants in phenotypes inherited in a Mendelian pattern, but biology is much more
      complex. Phenotypes are caused by the actions of several genes and epigenetic and
      environmental influences. Dissecting all influences necessitates ongoing and
      detailed phenotyping, refinement of clinical diagnostic assignments, and
      iterative analyses of NGS data. We conclude that there will be a critical need
      for phenotyping and clinical analysis, and that medical geneticists are uniquely
      positioned to address this need.

PMID- 22457029
TI  - A cycle of success: the interdependence of surgery and science.

PMID- 22457031
TI  - Easy operation for a huge coronary artery aneurysm.

PMID- 22457032
TI  - Penile prosthesis implantation for the treatment for male erectile dysfunction:
      clinical outcomes and lessons learnt after 955 procedures.
AB  - PURPOSE: To evaluate the clinical outcomes of penile prosthesis implantation for
      the treatment for erectile dysfunction (ED) over 3 decades in a centre of
      excellence. METHODS: A total of 955 penile prostheses were implanted between June
      1981 and June 2010. The mean age of the men was 53.2 (28-80) years, and the mean
      follow-up was 76 (12-355) months. A total of 771 men had primary implants. The
      most common implant was Ultrex cylinder (54 %), and the main cause of ED was
      organic (32 %). RESULTS: Primary implants showed higher rate of intra-operative
      complications than revision surgery (3.5 vs. 0.1 %) (p < 0.05). Prosthesis
      infection occurred in 0.8 % and equal incidence between diabetic and pelvic
      trauma patients. The average time to prosthetic revision was 102 (30-210) months.
      Kaplan-Meier estimates of overall penile prosthesis survival at 5 and 10 years
      were around 90.8 and 85.0 %. The most common mechanical failures were fluid loss
      (75 %). The majority of men were satisfied with the surgical outcomes, and 90 %
      of men would undergo penile prosthesis implant again. CONCLUSIONS: Penile
      prosthesis surgery is a safe and durable treatment option for male ED. Strict
      adherence to antimicrobial prophylaxis and surgical practice is paramount to
      ensure low complication rates and high patient satisfaction rate.

PMID- 22457033
TI  - Radical cystectomy with orthotopic neobladder reconstruction following prior
      radical prostatectomy.
AB  - PURPOSE: To review the perioperative and follow-up outcomes of patients
      undergoing radical cystectomy with orthotopic neobladder reconstruction for
      bladder cancer after prior radical prostatectomy (RP) for prostate cancer.
      METHODS: A retrospective review of more than 1,900 patients treated with radical
      cystectomy at USC between 1990 and 2011 was conducted. Fifty-six patients were
      identified who were previously treated with RP for prostate cancer. Twenty-four
      of these patients (43 %) underwent orthotopic neobladder reconstruction.
      Perioperative data and follow-up including postoperative continence were
      analyzed. RESULTS: The median age at cystectomy for these 24 patients was 68
      years (range 55-89). The types of neobladder reconstruction were Kock neobladder
      in 3, Sigmoid reservoir in 1, Studer neobladder in 12, and T-pouch ileal
      neobladder in 8 patients. There were no major intraoperative complications. Of 19
      patients eligible for evaluation of post-cystectomy urinary control, 11 patients
      (57.9 %) with good continence (0-1 pad/day) after RP regained preoperative level
      of urinary control after cystectomy within 1 year. The continence rate of 13 post
      RP patients with good continence was 84.6 %. Among the 4 patients who received
      adjuvant radiotherapy after RP, 1 regained good continence. One with poor
      continence after prostatectomy had an artificial urethral sphincter (AUS) placed
      2 months after cystectomy, and 2 with fair and poor continence after
      prostatectomy had an AUS placed at the time of cystectomy. CONCLUSIONS: Patients
      undergoing radical cystectomy after prior RP pose a challenge to urologists.
      Those who are continent post-RP have a fair chance of regaining good urinary
      control with neobladder reconstruction. Adjuvant radiotherapy for prostate cancer
      may have a negative impact on continence with neobladder reconstruction.

PMID- 22457034
TI  - Allergic bronchopulmonary aspergillosis with aspergilloma: an immunologically
      severe disease with poor outcome.
AB  - BACKGROUND AND AIMS: The association between allergic bronchopulmonary
      aspergillosis (ABPA) and aspergilloma has been proposed as a severe form of ABPA.
      However, this conclusion is based on single-patient case reports. In this study,
      we describe the clinical details and immunological findings of this association
      and compare patients of ABPA with aspergilloma and those without. METHODS: This
      is a retrospective analysis of data of patients with ABPA managed in the Chest
      Clinic. We compared the clinical, radiological and immunological profile of
      patients with ABPA and central bronchiectasis, with and without the presence of
      aspergilloma on HRCT scan. RESULTS: There were 98 men and 81 women with a mean
      (SD) age of 33.6 (12.2) years. Eight patients were diagnosed to have
      aspergilloma. Sputum cultures grew Aspergillus fumigatus in all these eight
      patients. The aspergilloma was solitary in six patients, and two each in two
      patients. Patients with aspergilloma had higher IgE levels (both total and A.
      fumigatus specific) than those without aspergilloma. Bronchiectasis was also more
      extensive in patients with aspergilloma. Overall, 70 % of the ABPA patients
      experienced relapse during the median (interquartile range) follow-up of 27 (19
      39) months. The number of relapses was significantly higher in patients with
      aspergilloma (p = 0.0001). On a multivariate linear regression analysis, high
      attenuation mucus and aspergilloma were independent predictors of relapse
      frequency. CONCLUSIONS: The concurrent presentation of ABPA and aspergilloma is
      associated with an immunologically severe disease and risk of recurrent relapses.

PMID- 22457038
TI  - The weakness of the strong/weak comparison of modes of inquiry.

PMID- 22457039
TI  - Prolonged electrical quiescence after direct current cardioversion for atrial
      flutter in congenital heart disease.
AB  - Elective direct current cardioversion is considered first-line treatment in many
      cases of atrial flutter and fibrillation. This also is true in the pediatric
      population. This report describes a case of successful cardioversion that
      resulted in a very prolonged electrical quiescence.

PMID- 22457040
TI  - Impact of polyelectrolytes and their corresponding multilayers to human primary
      endothelial cells.
AB  - The layer-by-layer technique, which allows simple preparation of polyelectrolyte
      multilayers, came into the focus of research for development of functionalized
      medical devices. Numerous literature exist that concentrate on the film build-up
      and the behaviour of cells on polyelectrolyte multilayers. However, in case of
      very soft polyelectrolyte multilayers, studies of the cell behaviour on these
      films are sometimes misleading with regard to clinical applications because cells
      do not die due to cytotoxicity but due to apoptosis by missing cell adhesion. It
      turns out that the adhesion in vitro, and thus, the viability of cells on
      polyelectrolyte multilayers is mostly influenced by their mechanical properties.
      In order to decide, which polyelectrolyte multilayers are suitable for implants,
      we take this problem into account by putting the substrates with soft films on
      top of pre-cultured human primary endothelial cells ('reverse assay'). Hence, the
      present work aims giving a more complete and reliable study of typical
      polyelectrolyte multilayers with regard to clinical applications. In particular,
      coatings consisting of hyaluronic acid and chitosan as natural polymers and
      sulfonated polystyrene and polyallylamine hydrochlorite as synthetic polymers
      were studied. The adsorption of polyelectrolytes was characterized by physico
      chemical methods which show regular buildup. Biological examination of the native
      or modified polyelectrolyte multilayers was based on their effect to cell
      adhesion and morphology of endothelial cells by viability assays, immunostaining
      and scanning electron microscopy. Using the standard method, which is typically
      applied in literature--seeding cells on top of films--shows that the best
      adhesion and thus, viability can be achieved using sulfonated
      polystyrene/polyallylamine hydrochlorite. However, putting the films on top of
      endothelial cells reveals that hyaluronic acid/chitosan may also be suitable for
      clinical applications: This result is especially remarkable, since hyaluronic
      acid and chitosan mediate per se no cytotoxic effects, whereas the individual
      polyelectrolytes, sulfonated polystyrene and polyallylamine hydrochlorite, and
      their complexes show slight cytotoxicity.

PMID- 22457041
TI  - Differential cellular and microbial responses to nano-/micron-scale titanium
      surface roughness induced by hydrogen peroxide treatment.
AB  - This study investigated the effects of combined titanium nano-/micron-scale
      roughness, induced by hydrogen peroxide pre-treatments, on bone marrow stromal
      cell responses and Porphyromonas gingivalis adherence in vitro. Untreated
      surfaces exhibited nano-scale features, while hydrogen peroxide treatments
      promoted increased nano-/micron-scale roughness. Bone marrow stromal cell
      attachment and proliferation were maintained with 6 h and 24 h treatments, but
      significantly decreased on 1-week and 4-week-treated surfaces. Bone marrow
      stromal cells on 6 h-4 week-treated titanium demonstrated enhanced osteogenic
      differentiation versus untreated surfaces. P. gingivalis adherence was
      significantly increased on 24 h-4 week surfaces. Results suggest that 6 h but
      less than 24 h treatments maintain or promote bone marrow stromal cell responses
      while minimizing microbial adherence, potentially enhancing titanium surface bio
      activation for osseointegration. 

PMID- 22457043
TI  - Surface-functionalized diatom microcapsules for drug delivery of water-insoluble
      drugs.
AB  - Naturally available and biocompatible materials are potential substitutes for
      synthetic mesoporous materials as suitable drug carriers for the development of
      cost-effective drug delivery systems. This work investigates the application of a
      porous silica material derived from diatoms, also known as diatomaceous earth.
      The aim is to explore the surface functionalization of diatom microcapsules and
      their impact on the drug loading and release characteristics of water-insoluble
      drugs. Indomethacin was used as the model for poorly soluble drug. The surface
      modification on diatoms was performed with two organosilanes; 3
      aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene diamine
      and phosphonic acids (2-carboxyethyl-phosphonic acid and 16-phosphono
      hexadecanoic acid) providing organic surface hydrophilic and hydrophobic
      properties. Extensive characterizations using scanning electron microscopy, X-ray
      photoelectron spectroscopy and differential scanning calorimetry was performed to
      confirm covalent grafting of monolayer aminosilane and phosphonic acid on the
      diatom surfaces. Differences in loading capacity of diatoms (15-24%) and release
      time (6-15 days) were observed which is due to the presence of different
      functional groups on the surface. It was found that 2-carboxyethyl-phosphonic
      acid, 3-aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene
      diamine render diatom surfaces hydrophilic, due to polar carboxyl functional
      group (COOH) and active amine species (NH and NH2) that favor drug adsorption;
      better encapsulation efficiency and prolonged release of drugs, over the
      hydrophobic surface created by 16-phosphono-hexadecanoic acid. This work
      demonstrates diatom porous silica as a promising drug carrier, with possibility
      to further improve their performances by tailoring their surface functionalities
      to achieve the required drug loading and release characteristics for different
      therapeutic conditions. 

PMID- 22457042
TI  - In vivo chondrocyte and transforming growth factor-beta1 delivery using the
      thermosensitive chitosan/starch/beta-glycerol phosphate hydrogel.
AB  - In present study, the chitosan/starch/beta-glycerol phosphate hydrogel was
      investigated as an effective carrier for chondrocytes and delivery of
      transforming growth factor-beta1. In vitro study indicated that transforming
      growth factor-beta1 was released sustainably for 14 days with its biological
      activity to stimulate chondrocyte functions, as indicated by the strong
      expression of type II collagen protein. Subcutaneous implantation to rats
      revealed the strong expressions of type II collagen and aggrecan messenger
      ribonucleic acids, and also type II collagen protein was observed in the hydrogel
      in combination with transforming growth factor-beta1 within 2 weeks. Our
      collective results showed the potential of chitosan/starch/beta-glycerol
      phosphate hydrogel for effective delivery of chondrocytes and transforming growth
      factor-beta1, and preserve chondrocytes' phenotype and functions in vitro. 

PMID- 22457044
TI  - Patterns of lymph node metastasis and their influence on outcomes in patients
      with submandibular gland carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Little is known about lymph node metastasis and the
      extent of neck dissection (ND) in patients with submandibular gland (SMG)
      carcinoma. We therefore evaluated the metastatic topography of neck lymph nodes
      in patients with SMG carcinoma and the influence of metastases on tumor
      recurrence and patient survival. METHODS: The pattern of lymph node spread was
      analyzed in 64 patients with SMG carcinoma treated from January 1994 to January
      2009. Disease-free survival (DFS), overall survival (OS), and distant metastasis
      free survival (DMFS) were calculated, and the clinicopathological factors
      associated with each were analyzed. RESULTS: Positive pathological lymph nodes
      were detected in 31 (48.4%) patients and was found to correlate significantly
      with histologic grade (P<0.001) on univariate analysis. Eight patients (19.5%)
      had occult cervical metastases. The 5-year DFS, OS, and DMFS rates were 46.8,
      56.2, and 58.5%, respectively, and 23 patients (35.9%) experienced systemic
      failure. Multivariate analyses revealed that T-classification (P=0.043) and N
      classification (P=0.006) were significantly independent predictors of DFS,
      whereas only N-classification (P=0.049) was significantly associated with DMFS.
      CONCLUSIONS: Elective ND should be recommended for preoperatively suspected high
      grade malignancy in SMG carcinoma. Patients with nodal metastasis should receive
      more effective therapy to hinder recurrence and distant metastasis.

PMID- 22457045
TI  - Electroretinographic findings associated with panretinal photocoagulation (PRP)
      versus PRP plus intravitreal ranibizumab treatment for high-risk proliferative
      diabetic retinopathy.
AB  - To evaluate changes in electroretinographic (ERG) findings after panretinal
      photocoagulation (PRP) compared to PRP plus intravitreal injection of ranibizumab
      (IVR) in eyes with high-risk proliferative diabetic retinopathy (PDR). Patients
      with high-risk PDR and no prior laser treatment were assigned randomly to receive
      PRP (PRP group; n = 9) or PRP plus IVR (PRPplus group; n = 11). PRP was
      administered in two sessions (weeks 0 and 2), and IVR was administered at the end
      of the first laser session (week 0) in the PRPplus group. Standardized ophthalmic
      evaluations including (ETDRS) best-corrected visual acuity (BCVA), and
      fluorescein angiography to measure area of fluorescein leakage (FLA), were
      performed at baseline and at weeks 16 (+/-2), 32 (+/-2) and 48 (+/-2). ERG was
      measured according to ISCEV standards at baseline and at week 48 (+/-2). At 48
      weeks, 2,400-3,000 laser spots had been placed in eyes in the PRP group, while
      only 1,400-1,800 spots had been placed in the PRPplus group. Compared to
      baseline, there was a statistically significant (P < 0.05) FLA reduction observed
      at all study visits in both groups, with the reduction observed in the PRPplus
      group significantly larger than that in the PRP group at week 48. ROD b-wave
      amplitude was significantly reduced to 46 +/- 5% (P < 0.05) of baseline in the
      PRP group and 64 +/- 6% (P < 0.05) in the PRPplus group. This reduction was
      significantly larger in the PRP group than in the PRPplus group (P = 0.024; t
      Test). Similar results were observed for the dark-adapted Combined Response (CR)
      b-wave amplitude, with a reduction at 48 weeks compared to baseline of 45 +/- 4%
      in the PRP group and 62 +/- 5% in the PRPplus group; the reduction in CR b-wave
      amplitude was significantly larger in the PRP group than in the PRPplus group (P
      = 0.0094). CR a-wave, oscillatory potentials, cone single flash, and 30 Hz
      flicker responses showed statistically significant within-group reductions, but
      no differences in between-group analyses. These results suggest that treating
      high-risk PDR with PRP plus IVR is effective for PDR control, and permits the use
      of less extensive PRP which, in turn, induces less retinal functional loss, in
      particular for rod-driven post-receptoral responses, than treatment with PRP
      alone.

PMID- 22457046
TI  - On- and off-response ERGs elicited by sawtooth stimuli in normal subjects and
      glaucoma patients.
AB  - The aim of this study is to measure the on- and off-responses and their response
      asymmetries elicited by sawtooth stimuli in normal subjects and glaucoma
      patients. Furthermore, the correlation between the ERGs and other functional and
      structural parameters are investigated. Full-field stimuli were produced using a
      Ganzfeld bowl with Light Emitting Diodes (LEDs) as light sources. On- and off
      response ERGs were recorded from 17 healthy subjects, 12 pre-perimetric and 15
      perimetric glaucoma patients using 4-Hz luminance rapid-on and rapid-off sawtooth
      stimuli (white light; mean luminance 55 cd/m(2)) at 100% contrast. The on- and
      off-responses were added to study response asymmetries. In addition, flash ERGs
      were elicited by red stimuli (200 cd/m(2)) on a blue background (10 cd/m(2)). The
      mean deviations (MD) of the visual field defects were obtained by standard
      automated perimetry. The retinal nerve fibre layer thickness (RNFLT) was measured
      with Spectral Domain Optical Coherence Tomography (SOCT). We studied the
      correlation between ERG response amplitudes, visual field mean deviation (MDs)
      and RNFLT values. The on-responses showed an initial negative (N-on) followed by
      a positive (P-on), a late positive (LP-on) and a late negative responses (LN-on).
      The off-responses showed an initial positive (P-off) a late positive (LP-off) and
      a late negative response (LN-off). The addition of on- and off-responses revealed
      an initial positive (P-add) and a late negative response (LN-add). The on
      response components (N-on, P-on and LN-on) in the glaucoma patients were
      relatively similar to those of the control subjects. However, the LP-on was
      significantly elevated (p = 0.03) in perimetric patients. The LP-off was
      significantly elevated (p < 0.001), and the amplitude of LN-off was significantly
      reduced in perimetric patients (p = 0.02). The LN-add amplitude was significantly
      reduced (p < 0.001) and delayed (p = 0.03) in perimetric patients. The amplitudes
      of the LN-off and LN-add ERG components were significantly correlated with the
      PhNR in the flash ERG (LN-off: p = 0.01; LN-add: p < 0.001) and with RNFLT (LN
      off: p = 0.006; LN-add: p = 0.001). On- and off-response ERGs and their response
      asymmetries, elicited by sawtooth stimuli, are altered in the glaucoma patients.
      The late components are affected. Changes in the late negative components are
      correlated with structural and other functional changes.

PMID- 22457047
TI  - Salivary cortisol and the diagnosis of Cushing's syndrome: a coming of age.

PMID- 22457048
TI  - Pathology in Africa: back to basics.

PMID- 22457049
TI  - Genome-wide analysis of DNA methylation identifies novel cancer-related genes in
      hepatocellular carcinoma.
AB  - Aberrant DNA methylation has been implicated in the development of hepatocellular
      carcinoma (HCC). Our aim was to clarify its molecular mechanism and to identify
      useful biomarkers by screening for DNA methylation in HCC. Methylated CpG island
      amplification coupled with CpG island microarray (MCAM) analysis was carried out
      to screen for methylated genes in primary HCC specimens [hepatitis B virus (HBV)
      positive, n = 4; hepatitis C virus (HCV)-positive, n = 5; HBV/HCV-negative, n =
      7]. Bisulfite pyrosequencing was used to analyze the methylation of selected
      genes and long interspersed nuclear element (LINE)-1 in HCC tissue (n = 57) and
      noncancerous liver tissue (n = 50) from HCC patients and in HCC cell lines (n =
      10). MCAM analysis identified 332, 342, and 259 genes that were methylated in HBV
      positive, HCV-positive, and HBV/HCV-negative HCC tissues, respectively. Among
      these genes, methylation of KLHL35, PAX5, PENK, and SPDYA was significantly
      higher in HCC tissue than in noncancerous liver tissue, irrespective of the
      hepatitis virus status. LINE-1 hypomethylation was also prevalent in HCC and
      correlated positively with KLHL35 and SPDYA methylation. Receiver operating
      characteristic curve analysis revealed that methylation of the four genes and
      LINE-1 strongly discriminated between HCC tissue and noncancerous liver tissue.
      Our data suggest that aberrant hyper- and hypomethylation may contribute to a
      common pathogenesis mechanism in HCC. Hypermethylation of KLHL35, PAX, PENK, and
      SDPYA and hypomethylation of LINE-1 could be useful biomarkers for the detection
      of HCC.

PMID- 22457050
TI  - Association between EGF +61 genetic polymorphisms and non-small cell lung cancer
      increased risk in a Portuguese population: a case-control study.
AB  - Epidermal growth factor (EGF) and its receptor play critical roles in non-small
      cell lung cancer (NSCLC) carcinogenesis. A functional polymorphism in the EGF
      gene has been linked to increased cancer susceptibility. This study aimed to
      evaluate the role of the EGF +61A/G polymorphism as risk factors in NSCLC
      patients. For the present case-control study, we analyzed 112 NSCLC and 126
      cancer-free controls from Portugal. Following DNA isolation from peripheral
      blood, EGF +61A/G polymorphism was assessed by polymerase chain reaction
      restriction fragment length polymorphism. Univariate and multivariate logistic
      regression analyses were used to calculate odds ratio (OR) and 95 % confidence
      intervals (95 % CI). False-positive report probability was also assessed. The EGF
      +61 genotypes frequencies in NSCLC were AA (23.2 %), AG (51.8 %), and GG (25 %)
      and in controls, AA (40.5 %), AG (41.3 %), and GG (18.3 %). When compared to the
      reference genotype (EGF +61A/A), we found a statistically significant association
      between EGF +61 A/G (OR = 2.142, 95 % CI 1.170-3.924) and EGF +61G/G (OR = 2.398,
      95 % CI 1.157-4.968) genotypes and susceptibility to development of NSCLC.
      Furthermore, stratification by sex revealed a trend to increased risk of males
      carrying +61A/G genotype for developing NSCLC (OR = 2.044, 95 % CI 0.998-4.188)
      when compared to A/A genotype. Our data suggest an increased risk to develop
      NSCLC in Portuguese population carrying the EGF +61A/G and +61G/G genotypes.

PMID- 22457051
TI  - Novel mutations in the KCND3-encoded Kv4.3 K+ channel associated with autopsy
      negative sudden unexplained death.
AB  - Heritable arrhythmia syndromes, including Brugada syndrome (BrS) and idiopathic
      ventricular fibrillation (IVF), may serve as the pathogenic basis for autopsy
      negative sudden unexplained death (SUD) and sudden infant death syndrome (SIDS).
      Emerging evidence has linked perturbations in the transient outward current
      (I(to) ) conducted by the KCND3-encoded Kv4.3 pore-forming alpha-subunit to BrS
      or IVF. However, the contribution of KCND3 mutations to autopsy-negative SUD/SIDS
      is unknown. To investigate the potential association between KCND3 and SUD/SIDS,
      mutational analysis of KCND3 was conducted in 123 SUDS and 292 SIDS victims using
      polymerase chain reaction, denaturing high-performance liquid chromatography, and
      direct sequencing. Overall, one SIDS case (<1.0%) and two SUDS cases (1.6%)
      harbored potentially pathogenic mutations in KCND3. The novel p.Val392Ile,
      p.Ser530Pro, and p.Gly600Arg mutations involved highly conserved residues and
      were absent in 1,560 reference alleles. Although the SIDS-associated p.Ser530Pro
      mutation demonstrated a wild-type (WT) electrophysiological phenotype when
      heterologously expressed, the SUDS-associated p.Val392Ile and p.Gly600Arg
      mutations significantly increased peak current density at +40 mV in comparison
      with WT by 100.4% (P < 0.05) and 50.4% (P < 0.05), respectively. p.Val392Ile also
      slowed recovery from inactivation 3.6-fold, indicating a mixed
      electrophysiological phenotype. This is the first report indicating that KCND3
      may serve as a rare genetic substrate in the pathogenesis of SUDS but not SIDS
      cases.

PMID- 22457052
TI  - Potential for osteogenic and chondrogenic differentiation of MSC.
AB  - The introduction of mesenchymal stem cells (MSC) into the field of tissue
      engineering for bone and cartilage repair is a promising development, since these
      cells can be expanded ex vivo to clinically relevant numbers and, after
      expansion, retain their ability to differentiate into different cell lineages.
      Mesenchymal stem cells isolated from various tissues have been intensively
      studied and characterized by many research groups. To obtain functionally active
      differentiated tissue, tissue engineered constructs are cultivated in vitro
      statically or dynamically in bioreactors under controlled conditions. These
      conditions include special cell culture media, addition of signalling molecules,
      various physical and chemical factors and the application of different mechanical
      stimuli. Oxygen concentration in the culture environment is also a significant
      factor which influences MSC proliferation, stemness and differentiation capacity.
      Knowledge of the different aspects which affect MSC differentiation in vivo and
      in vitro will help researchers to achieve directed cell fate without the addition
      of differentiation agents in concentrations above the physiological range.

PMID- 22457059
TI  - Urethral pressure reflectometry before and after tension-free vaginal tape.
AB  - AIM: Urethral pressure reflectometry (UPR) is a new method for measuring pressure
      and cross-sectional area in the urethra. Our aim was to investigate if the UPR
      parameters at rest and during squeeze were unchanged after TVT. METHODS: The
      technique enables measurement along the entire length of the urethra
      simultaneously and avoids the common artefacts encountered with conventional
      catheters. Twenty-two stress urinary incontinent women were included. The UPR
      polyurethane bag was placed in the urethra and connected to a pump and an
      acoustic transmitter. The bag was inflated, distending it accordingly, and the CA
      within the bag, and thus the urethra, was measured with acoustic reflectometry.
      Opening and closing pressure and elastance, and hysteresis were measured.
      "Relaxing" and "squeezing" measurements were conducted in the supine and standing
      position before and after TVT. RESULTS: Subjective and objective cure rates were
      82% and 100%, respectively. Maximum urine flow rate decreased from 31 to 18
      ml/sec (P = 0.0002). Supine and standing relaxing urethral opening and closing
      pressures were unchanged. Supine opening elastance increased 18% (P = 0.04),
      which indicates an increased resistance against the opening of the urethra.
      Supine squeezing opening pressure decreased 10%. CONCLUSIONS: UPR measurements
      confirmed that urethral opening pressure at rest is unchanged after TVT. The TVT
      somewhat improves the closure function by providing increased resistance against
      the dilation of the urethra, which probably explains the decreased maximum urine
      flow rate.

PMID- 22457060
TI  - Molecular dynamics extended for fluctuating networks: application to water.
AB  - Molecular simulation models are increasingly important tools in efforts to
      understand the role that water plays in biochemical processes. However, existing
      models of water have limited capacity to deal with the characteristics of
      hydrogen bond networks. This article proposes a new fluctuating network (FN)
      algorithm as an extension of the standard molecular dynamics algorithm. The new
      algorithm allows for the simulation of a molecular system based on an underlying
      network, such as the hydrogen bond network in water. This algorithm distinguishes
      strong from weak network connections, applying a potential that best describes
      the specific connection behavior. We model liquid water with this new technique
      using a single-site, isotropic, short-range potential. We successfully reproduce
      liquid water's signature molecular spacing (as represented by the radial
      distribution function) and characterize its dynamic properties including the
      exponential hydrogen bond lifetime distribution, diffusion rate, and average
      hydrogen bonds per molecule. The FN algorithm allows exploration of the behavior
      of networked systems where explicit coordination limits are required. As such it
      could also be used to model covalent interactions, reaction dynamics, and applied
      to simulation of cellular networks.

PMID- 22457061
TI  - The cognitive capabilities of farm animals: categorisation learning in dwarf
      goats (Capra hircus).
AB  - The ability to establish categories enables organisms to classify stimuli,
      objects and events by assessing perceptual, associative or rational similarities
      and provides the basis for higher cognitive processing. The cognitive
      capabilities of farm animals are receiving increasing attention in applied
      ethology, a development driven primarily by scientifically based efforts to
      improve animal welfare. The present study investigated the learning of perceptual
      categories in Nigerian dwarf goats (Capra hircus) by using an automated learning
      device installed in the animals' pen. Thirteen group-housed goats were trained in
      a closed-economy approach to discriminate artificial two-dimensional symbols
      presented in a four-choice design. The symbols belonged to two categories:
      category I, black symbols with an open centre (rewarded) and category II, the
      same symbols but filled black (unrewarded). One symbol from category I and three
      different symbols from category II were used to define a discrimination problem.
      After the training of eight problems, the animals were presented with a transfer
      series containing the training problems interspersed with completely new problems
      made from new symbols belonging to the same categories. The results clearly
      demonstrate that dwarf goats are able to form categories based on similarities in
      the visual appearance of artificial symbols and to generalise across new symbols.
      However, the goats had difficulties in discriminating specific symbols. It is
      probable that perceptual problems caused these difficulties. Nevertheless, the
      present study suggests that goats housed under farming conditions have well
      developed cognitive abilities, including learning of open-ended categories. This
      result could prove beneficial by facilitating animals' adaptation to housing
      environments that favour their cognitive capabilities.

PMID- 22457062
TI  - Usual and unusual causes of pediatric gastric outlet obstruction.
AB  - Gastric outlet obstruction in children encompasses a spectrum of disorders that
      extends beyond hypertrophic pyloric stenosis. Each condition can result in the
      clinical syndrome of persistent nonbilious vomiting, which can progress to
      dehydration and electrolyte imbalances. This paper reviews the spectrum of both
      the common and uncommon entities that cause partial or complete gastric outlet
      obstruction and their imaging appearances. The correct diagnosis of those with
      gastric outlet obstruction can be achieved by combining clinical presentation
      with appropriate imaging, leading to optimal and timely patient management.

PMID- 22457063
TI  - Comparative analysis of human and mouse expression data illuminates tissue
      specific evolutionary patterns of miRNAs.
AB  - MicroRNAs (miRNAs) constitute an important class of gene regulators. While models
      have been proposed to explain their appearance and expansion, the validation of
      these models has been difficult due to the lack of comparative studies. Here, we
      analyze miRNA evolutionary patterns in two mammals, human and mouse, in relation
      to the age of miRNA families. In this comparative framework, we confirm some
      predictions of previously advanced models of miRNA evolution, e.g. that miRNAs
      arise more frequently de novo than by duplication, or that the number of protein
      coding gene targeted by miRNAs decreases with evolutionary time. We also
      corroborate that miRNAs display an increase in expression level with evolutionary
      time, however we show that this relation is largely tissue-dependent, and
      especially low in embryonic or nervous tissues. We identify a bias of tag
      sequencing techniques regarding the assessment of breadth of expression, leading
      us, contrary to predictions, to find more tissue-specific expression of older
      miRNAs. Together, our results refine the models used so far to depict the
      evolution of miRNA genes. They underline the role of tissue-specific selective
      forces on the evolution of miRNAs, as well as the potential co-evolution patterns
      between miRNAs and the protein-coding genes they target.

PMID- 22457064
TI  - Evolutionary and genetic analyses of mitochondrial translation initiation factors
      identify the missing mitochondrial IF3 in S. cerevisiae.
AB  - Mitochondrial translation is essentially bacteria-like, reflecting the bacterial
      endosymbiotic ancestry of the eukaryotic organelle. However, unlike the
      translation system of its bacterial ancestors, mitochondrial translation is
      limited to just a few mRNAs, mainly coding for components of the respiratory
      complex. The classical bacterial initiation factors (IFs) IF1, IF2 and IF3 are
      universal in bacteria, but only IF2 is universal in mitochondria (mIF2). We
      analyse the distribution of mitochondrial translation initiation factors and
      their sequence features, given two well-propagated claims: first, a sequence
      insertion in mitochondrial IF2 (mIF2) compensates for the universal lack of IF1
      in mitochondria, and secondly, no homologue of mitochondrial IF3 (mIF3) is
      identifiable in Saccharomyces cerevisiae. Our comparative sequence analysis shows
      that, in fact, the mIF2 insertion is highly variable and restricted in length and
      primary sequence conservation to vertebrates, while phylogenetic and in vivo
      complementation analyses reveal that an uncharacterized S. cerevisiae
      mitochondrial protein currently named Aim23p is a bona fide evolutionary and
      functional orthologue of mIF3. Our results highlight the lineage-specific nature
      of mitochondrial translation and emphasise that comparative analyses among
      diverse taxa are essential for understanding whether generalizations from model
      organisms can be made across eukaryotes.

PMID- 22457065
TI  - Fast production of homogeneous recombinant RNA--towards large-scale production of
      RNA.
AB  - In the past decades, RNA molecules have emerged as important players in numerous
      cellular processes. To understand these processes at the molecular and atomic
      level, large amounts of homogeneous RNA are required for structural, biochemical
      and pharmacological investigations. Such RNAs are generally obtained from
      laborious and costly in vitro transcriptions or chemical synthesis. In 2007, a
      recombinant RNA technology has been described for the constitutive production of
      large amounts of recombinant RNA in Escherichia coli using a tRNA-scaffold
      approach. We demonstrate a general applicable extension to the described approach
      by introducing the following improvements: (i) enhanced transcription of large
      recombinant RNAs by T7 RNA polymerase (high transcription rates, versatile), (ii)
      efficient and facile excision of the RNA of interest from the tRNA-scaffold by
      dual cis-acting hammerhead ribozyme mediated cleavage and (iii) rapid
      purification of the RNA of interest employing anion-exchange chromatography or
      affinity chromatography followed by denaturing polyacrylamide gel
      electrophoresis. These improvements in the existing method pave the tRNA-scaffold
      approach further such that any (non-)structured product RNA of a defined length
      can cost-efficiently be obtained in (multi-)milligram quantities without in vitro
      enzymatic manipulations.

PMID- 22457066
TI  - Role of SUMO modification of human PCNA at stalled replication fork.
AB  - DNA double-strand breaks (DSBs) can be generated not only by reactive agents but
      also as a result of replication fork collapse at unrepaired DNA lesions. Whereas
      ubiquitylation of proliferating cell nuclear antigen (PCNA) facilitates damage
      bypass, modification of yeast PCNA by small ubiquitin-like modifier (SUMO)
      controls recombination by providing access for the Srs2 helicase to disrupt Rad51
      nucleoprotein filaments. However, in human cells, the roles of PCNA SUMOylation
      have not been explored. Here, we characterize the modification of human PCNA by
      SUMO in vivo as well as in vitro. We establish that human PCNA can be SUMOylated
      at multiple sites including its highly conserved K164 residue and that SUMO
      modification is facilitated by replication factor C (RFC). We also show that
      expression of SUMOylation site PCNA mutants leads to increased DSB formation in
      the Rad18(-/-) cell line where the effect of Rad18-dependent K164 PCNA
      ubiquitylation can be ruled out. Moreover, expression of PCNA-SUMO1 fusion
      prevents DSB formation as well as inhibits recombination if replication stalls at
      DNA lesions. These findings suggest the importance of SUMO modification of human
      PCNA in preventing replication fork collapse to DSB and providing genome
      stability.

PMID- 22457067
TI  - The eukaryotic initiation factor eIF4H facilitates loop-binding, repetitive RNA
      unwinding by the eIF4A DEAD-box helicase.
AB  - Eukaryotic translation initiation is a highly regulated process in protein
      synthesis. The principal translation initiation factor eIF4AI displays helicase
      activity, unwinding secondary structures in the mRNAs 5'-UTR. Single molecule
      fluorescence resonance energy transfer (sm-FRET) is applied here to directly
      observe and quantify the helicase activity of eIF4AI in the presence of the
      ancillary RNA-binding factor eIF4H. Results show that eIF4H can significantly
      enhance the helicase activity of eIF4AI by strongly binding both to loop
      structures within the RNA transcript as well as to eIF4AI. In the presence of
      ATP, the eIF4AI/eIF4H complex exhibits persistent rapid and repetitive cycles of
      unwinding and re-annealing. ATP titration assays suggest that this process
      consumes a single ATP molecule per cycle. In contrast, helicase unwinding
      activity does not occur in the presence of the non-hydrolysable analog ATP
      gammaS. Based on our sm-FRET results, we propose an unwinding mechanism where
      eIF4AI/eIF4H can bind directly to loop structures to destabilize duplexes. Since
      eIF4AI is the prototypical example of a DEA(D/H)-box RNA helicase, it is highly
      likely that this unwinding mechanism is applicable to a myriad of DEAD-box
      helicases employed in RNA metabolism.

PMID- 22457069
TI  - Fluorescence-based incision assay for human XPF-ERCC1 activity identifies
      important elements of DNA junction recognition.
AB  - The structure-specific endonuclease activity of the human XPF-ERCC1 complex is
      essential for a number of DNA processing mechanisms that help to maintain genomic
      integrity. XPF-ERCC1 cleaves DNA structures such as stem-loops, bubbles or flaps
      in one strand of a duplex where there is at least one downstream single strand.
      Here, we define the minimal substrate requirements for cleavage of stem-loop
      substrates allowing us to develop a real-time fluorescence-based assay to measure
      endonuclease activity. Using this assay, we show that changes in the sequence of
      the duplex upstream of the incision site results in up to 100-fold variation in
      cleavage rate of a stem-loop substrate by XPF-ERCC1. XPF-ERCC1 has a preference
      for cleaving the phosphodiester bond positioned on the 3'-side of a T or a U,
      which is flanked by an upstream T or U suggesting that a T/U pocket may exist
      within the catalytic domain. In addition to an endonuclease domain and tandem
      helix-hairpin-helix domains, XPF has a divergent and inactive DEAH helicase-like
      domain (HLD). We show that deletion of HLD eliminates endonuclease activity and
      demonstrate that purified recombinant XPF-HLD shows a preference for binding stem
      loop structures over single strand or duplex alone, suggesting a role for the HLD
      in initial structure recognition. Together our data describe features of XPF
      ERCC1 and an accepted model substrate that are important for recognition and
      efficient incision activity.

PMID- 22457070
TI  - A mostly traditional approach improves alignment of bisulfite-converted DNA.
AB  - Cytosines in genomic DNA are sometimes methylated. This affects many biological
      processes and diseases. The standard way of measuring methylation is to use
      bisulfite, which converts unmethylated cytosines to thymines, then sequence the
      DNA and compare it to a reference genome sequence. We describe a method for the
      critical step of aligning the DNA reads to the correct genomic locations. Our
      method builds on classic alignment techniques, including likelihood-ratio scores
      and spaced seeds. In a realistic benchmark, our method has a better combination
      of sensitivity, specificity and speed than nine other high-throughput bisulfite
      aligners. This study enables more accurate and rational analysis of DNA
      methylation. It also illustrates how to adapt general-purpose alignment methods
      to a special case with distorted base patterns: this should be informative for
      other special cases such as ancient DNA and AT-rich genomes.

PMID- 22457068
TI  - Transient structure and dynamics in the disordered c-Myc transactivation domain
      affect Bin1 binding.
AB  - The crucial role of Myc as an oncoprotein and as a key regulator of cell growth
      makes it essential to understand the molecular basis of Myc function. The N
      terminal region of c-Myc coordinates a wealth of protein interactions involved in
      transformation, differentiation and apoptosis. We have characterized in detail
      the intrinsically disordered properties of Myc-1-88, where hierarchical
      phosphorylation of S62 and T58 regulates activation and destruction of the Myc
      protein. By nuclear magnetic resonance (NMR) chemical shift analysis, relaxation
      measurements and NOE analysis, we show that although Myc occupies a very
      heterogeneous conformational space, we find transiently structured regions in
      residues 22-33 and in the Myc homology box I (MBI; residues 45-65); both these
      regions are conserved in other members of the Myc family. Binding of Bin1 to Myc
      1-88 as assayed by NMR and surface plasmon resonance (SPR) revealed primary
      binding to the S62 region in a dynamically disordered and multivalent complex,
      accompanied by population shifts leading to altered intramolecular conformational
      dynamics. These findings expand the increasingly recognized concept of
      intrinsically disordered regions mediating transient interactions to Myc, a key
      transcriptional regulator of major medical importance, and have important
      implications for further understanding its multifaceted role in gene regulation.

PMID- 22457071
TI  - Functional interaction between the Arabidopsis orthologs of spindle assembly
      checkpoint proteins MAD1 and MAD2 and the nucleoporin NUA.
AB  - In eukaryotes, the spindle assembly checkpoint (SAC) ensures the fidelity of
      chromosome segregation through monitoring the bipolar attachment of microtubules
      to kinetochores. Recently, the SAC components Mitotic Arrest Deficient 1 and 2
      (MAD1 and MAD2) were found to associate with the nuclear pore complex (NPC)
      during interphase and to require certain nucleoporins, such as Tpr in animal
      cells, to properly localize to kinetochores. In plants, the SAC components MAD2,
      BUR1, BUB3 and Mps1 have been identified, but their connection to the nuclear
      pore has not been explored. Here, we show that AtMAD1 and AtMAD2 are associated
      with the nuclear envelope during interphase, requiring the Arabidopsis homolog of
      Tpr, NUA. Both NUA and AtMAD2 loss-of-function mutants have a shorter primary
      root and a smaller root meristem, and this defect can be partially rescued by
      sucrose. Mild AtMAD2 over-expressors exhibit a longer primary root, and an
      extended root meristem. In BY-2 cells, AtMAD2 is associated with kinetochores
      during prophase and prometaphase, but not metaphase, anaphase and telophase.
      Protein-interaction assays demonstrate binding of AtMAD2 to AtMAD1 and AtMAD1 to
      NUA. Together, these data suggest that NUA scaffolds AtMAD1 and AtMAD2 at the
      nuclear pore to form a functional complex and that both NUA and AtMAD2 suppress
      premature exit from cell division at the Arabidopsis root meristem.

PMID- 22457074
TI  - Saccadic tracking of targets mediated by the anterior-lateral eyes of jumping
      spiders.
AB  - The modular visual system of jumping spiders (Salticidae) divides characteristics
      such as high spatial acuity and wide-field motion detection between different
      pairs of eyes. A large pair of telescope-like anterior-median (AM) eyes is
      supported by 2-3 pairs of 'secondary' eyes, which provide almost 360 degrees of
      visual coverage at lower resolution. The AM retinae are moveable and can be
      pointed at stimuli within their range of motion, but salticids have to turn to
      bring targets into this frontal zone in the first place. We describe how the
      front-facing pair of secondary eyes (anterior lateral, AL) mediates this through
      a series of whole-body 'tracking saccades' in response to computer-generated
      stimuli. We investigated the 'response area' of the AL eyes and show a clear
      correspondence between the physical margins of the retina and stimulus position
      at the onset of the first saccade. Saccade frequency is maximal at the margin of
      AL and AM fields of view. Furthermore, spiders markedly increase the velocity
      with which higher magnitude tracking saccades are carried out. This has the
      effect that the time during which vision is impaired due to motion blur is kept
      at an almost constant low level, even during saccades of large magnitude.

PMID- 22457075
TI  - Effect of dietary calcium (Ca) on body composition and Ca metabolism during
      growth in genetically obese (beta) male rats.
AB  - INTRODUCTION: Obese beta rats may be a suitable model to evaluate the association
      between calcium intake (CaI) and obesity during growth. OBJECTIVE: The present
      study comparatively evaluated Ca absorption and retention, and changes in body
      composition in spontaneously genetically obese (beta) male rats fed three
      different dietary Ca levels: high 0.9% (HCa); normal: 0.5% (NCa); low: 0.2%
      (LCa). METHODS: Pregnant rats were fed isocaloric diets which varied in Ca
      content only. Male pups continued feeding the same maternal diet until postnatal
      day 60. The percentage of Apparent Ca absorption (CaA %), Ca balance (CaB), body
      composition, glucose, triglycerides (TGL), and insulin levels were evaluated.
      RESULTS: Food consumption and body weight (BW) were higher in Group LCa than in
      Groups NCa and HCa (p < 0.01); no differences were observed between the latter
      two groups. Group LCa presented the highest body fat, liver weight, perigonadal
      and retroperitoneal fat (p < 0.05); conversely, body ashes and total skeleton
      bone mineral content were significantly lower compared with animals in both the
      NCa (p < 0.01) and HCa groups (p < 0.01). CaB (mg/day) reached a plateau at the
      highest CaI (mg/day) value (r = 0.985, p < 0.001). CaA%, serum glucose, insulin,
      and TGL levels rose as CaI decreased (p < 0.01). CONCLUSIONS: Although further
      studies are required, low Ca consumption in this strain of rats could modulate BW
      inducing changes in several lipid metabolism parameters, which in turn lead to an
      increase in body fat.

PMID- 22457076
TI  - Attempted suicide with an axe: a hanged waiter with multiple healed chop wounds
      to the crown of the head.

PMID- 22457077
TI  - Growth and histopathological effects of chronic exposition of marine pejerrey
      Odontesthes argentinensis larvae to petroleum water-soluble fraction (WSF).
AB  - The water-soluble fraction (WSF) of petroleum contains a mixture of polycyclic
      aromatic hydrocarbons, volatile hydrocarbons, phenols, and heterocyclic
      compounds, considered deleterious to aquatic biota. Marine "pejerrey" Odontesthes
      argentinensis (Teleostei: Atherinopsidae) has a great commercial importance in
      local fisheries and a high potential for aquaculture. The aim of this study was
      to evaluate the histopathological effects in "pejerrey" larvae exposed to
      different concentrations of petroleum WSF. The chronic toxicity test was
      conducted with newly hatched larvae exposed for 21 days to sublethal
      concentrations of WSF (2.5, 5, 10, and 20 % of WSF), plus one control. Survival
      and growth were significantly lower in the highest concentration. Several
      histopathological changes were found in the gills (e.g., hyperplasia, aneurisms,
      edema, and necrosis), kidney (e.g., nuclear alterations, decrease in the
      hematopoietic cells), and liver (e.g., hypertrophy, karyorrhexis, and
      karyopyknosis). An index of branchial lesion was proposed to standardize gill
      lesions to different pollutants.

PMID- 22457078
TI  - China's Wetlands: conservation plans and policy impacts.

PMID- 22457079
TI  - What's the problem? River management, education, and public beliefs.
AB  - This paper invokes the theory of planned behavior (TPB) as a diagnostic tool to
      explain an existing public education program's limited success at improving river
      water quality in the City of Perth, Western Australia. A reflective, client
      driven research approach was used. A facilitated expert workshop defined an
      environmental problem (excess nutrients leaving gardens and entering waterways)
      and a desired behavior (residents purchasing environmentally sensitive
      fertilizer) to address the problem. A TPB-based belief elicitation survey
      captured respondents' beliefs regarding the desired behavior. The findings
      suggest respondents were aware of the links between purchasing environmentally
      sensitive fertilizer and river water quality. However, this behavior is
      compromised by the challenges in identifying appropriate products, product
      quality concerns, and cost. Viewing the content of a public education program
      through the lens of the TPB reveals insights into how and why the program fell
      short in achieving one of its key behavioral change goals.

PMID- 22457080
TI  - Non transmissible diseases are often transmissible.

PMID- 22457081
TI  - Metabolic acidosis mimicking diabetic ketoacidosis after use of calorie-free
      mineral water.
AB  - A previously healthy boy was admitted with fever, tachycardia, dyspnea, and was
      vomiting. A blood test showed a severe metabolic acidosis with pH 7.08 and an
      anion gap of 36 mmol/L. His urine had an odor of acetone. The serum glucose was
      5.6 mmol/L, and no glucosuria was found. Diabetic ketoacidosis could therefore be
      eliminated. Lactate level was normal. Tests for the most common metabolic
      diseases were negative. Because of herpes stomatitis, the boy had lost appetite
      and only been drinking Diet Coke and water the last days. Diet Coke or Coca-Cola
      Light is sweetened with a blend containing cyclamates, aspartame, and acesulfame
      potassium, all free of calories. The etiology of the metabolic acidosis appeared
      to be a catabolic situation exaggerated by fasting with no intake of calories.
      The elevated anion gap was due to a severe starvation ketoacidosis, mimicking a
      diabetic ketoacidosis. Pediatricians should recommend carbohydrate/calorie
      containing fluids for rehydration of children with acute fever, diarrhea, or
      illness.

PMID- 22457082
TI  - Comparing the reprogramming efficiency of mouse embryonic fibroblasts, mouse bone
      marrow mesenchymal stem cells and bone marrow mononuclear cells to iPSCs.
AB  - Induced pluripotent stem cells have been derived from various cell types via the
      ectopic expression of a cocktail of transcription factors. Previous studies have
      reported that induced pluripotent stem cells can be differentiated into multiple
      somatic cells, providing an invaluable resource in regenerative medicine. In this
      study, we compared the reprogramming efficiency of mouse embryonic fibroblasts,
      mouse bone marrow mesenchymal stem cells, and mouse bone marrow mononuclear cells
      by counting the number of alkaline phosphatase staining positive clones on day 15
      after induced pluripotent stem cells induction. We found that a very low number
      of alkaline phosphatase-staining positive clones were derived from mouse bone
      marrow mesenchymal stem cells. We then evaluated the pluripotency of the clones
      by detecting the expression of embryonic stem cells markers and assessing their
      ability to form embryoid bodies and teratomas. Mouse bone marrow mesenchymal stem
      cells population is more homogeneous than mouse bone marrow mononuclear cells,
      which includes a variety of cell types. Our study indicated that the extremely
      low efficiency of mouse bone marrow mesenchymal stem cells induction implies that
      mouse bone marrow mesenchymal stem cells may not be a suitable cell type for the
      induction of induced pluripotent stem cells unless the efficiency of induction
      can be improved.

PMID- 22457083
TI  - Effects of joint contracture on the contralateral unoperated limb in a rabbit
      knee contracture model: a biomechanical and genetic study.
AB  - In most animal models, unoperated contralateral limbs are used as controls.
      However, in some experimental circumstances, the contralateral limb may represent
      a skewed control. The main purpose of this study was to determine if the
      unoperated contralateral limb could be used as a control, or if a different
      unoperated animal's limb should be used instead. Seventeen rabbits were divided
      into two groups. Group 1 rabbits (n = 12) underwent surgery on their right limbs
      to induce a contracture. Group 2 rabbits (n = 5) underwent no surgery. The left
      non-operated limbs of rabbits in group 1 were biomechanically and genetically
      compared to the limbs of unoperated rabbits in group 2 with the use of a
      validated joint measuring device and custom microarray, respectively. After 8
      weeks of immobilization, there was a statistically greater flexion contracture in
      the unoperated contralateral limbs compared to the limbs of animals that received
      no surgery(8.4 +/- 8.9 degrees  vs. 0 +/- 0 degrees ; p-value = 0.03). When
      animals were remobilized for an additional 16 weeks, the significance between
      groups was lost (11.9 +/- 21.4 degrees  vs. 8.9 +/- 9.5 degrees ; p = 0.38).
      Similarly, there was a statistically significant increase in nine genes at 8
      weeks (p < 0.001). However, at 24 weeks, only the PMCA 1 gene was statically
      increased (p < 0.001). In our rabbit model, the non-operated limb develops a
      small flexion contracture at 8 weeks. After 16 weeks of remobilization, there is
      no biomechanical or genetic difference between contralateral non-operated limbs
      and limbs of animals not undergoing any surgical intervention. Given the
      biomechanical and genetic findings, the contralateral non-operated limb can be
      used as a valid control.

PMID- 22457084
TI  - Number of harvested lymph nodes is the main prognostic factor in Stage IIa
      colorectal cancer patients.
AB  - BACKGROUND: Current international guidelines on colorectal cancer (CRC) treatment
      suggest performing adjuvant chemotherapy only in Stage II patients presenting
      with high-risk prognostic factors. Aim of the study was to a the impact of these
      parameters on the survival of Stage IIa CRC patients, focusing on the prognostic
      value of the number of harvested lymph nodes (NHLN). PATIENTS AND METHODS: Out of
      651 CRC patients undergoing surgical resection, 204 T3-N0-M0 were selected and
      reviewed. Univariate and multivariate survival analyses were adapted for the
      evaluation of the prognostic factors. RESULTS: The 5 years actuarial DFS, DSS,
      and OS rates of patients with a NHLN >12 were significantly better compared to
      those of patients with a NHLN <12 (respectively: 72.8% vs. 50.4% P=0.001; 82% vs.
      56% P=0.001; 78.5% vs. 53.1% P=0.001). Multivariate analysis revealed that a NHLN
      >12 was the only independent parameter of statistical significance influencing
      DFS, DSS, and OS. CONCLUSIONS: According to our findings, the NHLN is the main
      predictor of survival in Stage IIa CRC patients. This would appear to suggest the
      need of a better stratification of Stage IIa CRC patients, sub-dividing patients
      with more or less than 12 NHLN.

PMID- 22457086
TI  - Serum levels of soluble secreted alpha-Klotho are decreased in the early stages
      of chronic kidney disease, making it a probable novel biomarker for early
      diagnosis.
AB  - BACKGROUND: alpha-Klotho was first identified as an aging gene and was later
      shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23
      (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble
      alpha-Klotho in chronic kidney disease (CKD) patients have not previously been
      determined, especially in relation with FGF23 and creatinine levels. This study
      was designed to investigate whether serum soluble alpha-Klotho levels are
      modulated by renal function, age, and FGF23 level in CKD patients. This study is
      the first report on the utility of measuring soluble alpha-Klotho levels in human
      CKD. METHODS: A total of 292 CKD patients were enrolled. Serum samples were
      collected, and FGF23 and soluble alpha-Klotho levels were measured using enzyme
      linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin,
      albumin, calcium, and phosphate levels were measured. RESULTS: Serum soluble
      alpha-Klotho levels were associated positively with estimated glomerular
      filtration rate (eGFR) (P < 0.0001) and inversely with serum creatinine level (P
      < 0.01). Interestingly, alpha-Klotho levels were significantly decreased in stage
      2 CKD compared with stage 1 (P = 0.0001). Serum FGF23 levels were associated
      positively with serum creatinine and negatively with eGFR. FGF23 levels were
      significantly increased in stage 5 compared with stage 1 CKD. Soluble alpha
      Klotho was associated inversely with log-transformed FGF23 level (P < 0.01).
      CONCLUSION: Our data indicate that soluble alpha-Klotho levels are significantly
      decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages
      of the disease. Soluble alpha-Klotho may thus represent a new biomarker for the
      diagnosis of CKD, especially in the early stage.

PMID- 22457088
TI  - Vitamin D receptor agonist supplementation and suppression of inflammation may
      have advantage for all-cause mortality in hemodialysis patients.
AB  - BACKGROUND: Vitamin D deficiency is common in hemodialysis (HD) patients. The aim
      of this study was to determine whether HD patients with low 25-hydroxyvitamin D
      [25(OH)D] levels are at increased risk of mortality. METHODS: This was a
      prospective cohort study of Japanese HD patients. We selected all patients with
      measured serum 25(OH)D levels at the time of entry. We assessed the impact of low
      serum 25(OH)D levels on the long-term mortality of HD patients by performing Cox
      regression analyses. Associations between serum 25(OH)D levels and all-cause
      mortality were also investigated. RESULTS: Data from 100 patients (mean age 61.0
      +/- 11.8 years, 64 % males) were available. There was a high prevalence (55 %) of
      25(OH)D insufficiency < 20 ng/ml, and 51 % of study subjects were treated with
      alfacalcidol. Twenty-four patients died during a follow-up period of 4.6 years.
      There were no significant associations between serum 25(OH)D levels and all-cause
      mortality (p = 0.777). After adjustments for possible confounders, the hazard
      ratio (with 95 % CI) for all-cause mortality was 1.091 (1.024-1.167) for age,
      0.734 (0.566-1.167) for dialysis vintage, 1.012 (0.995-1.031) for serum total
      cholesterol values, 2.028 (1.093-3.701) for serum phosphate levels, and 0.291
      (0.088-0.855) for treatment with alfacalcidol. A survival advantage of
      alfacalcidol treatment was observed (log-rank, p = 0.0150). The group of subjects
      whose serum (25(OH)D level was <20 ng/ml and who were not treated with
      alfacalcidol had the highest mortality rate. CONCLUSION: Vitamin D deficiency in
      HD patients who had not taken vitamin D receptor agonist (VDRA) is associated
      with an increased risk of all-cause mortality. VDRA supplementation may suppress
      chronic inflammation and have some advantage for mortality of HD patients with
      vitamin D deficiency.

PMID- 22457087
TI  - Perioperative fluid balance and acute kidney injury.
AB  - BACKGROUND: Positive fluid balance (FB) has been linked to adverse clinical
      outcomes. We performed this study to explore the relationship between
      perioperative fluid balance and acute kidney injury (AKI). METHODS: The
      relationships between FB and AKI were explored using a prospective, observational
      design. Patients were divided into quartiles based on FB status in the first 24 h
      from initiation of surgery in order to further explore this relationship.
      RESULTS: One hundred adult patients undergoing cardiovascular surgery were
      included in the analysis. The major finding of the study was that positive FB
      occurred early in the intraoperative period and progressed into the postoperative
      period and that fluid administration was not clearly associated with any
      identifiable volume-sensitive event. The evolution of positive FB preceded the
      rise in serum creatinine. Progressive severity of positive FB was associated with
      increased incidence of AKI. The highest quartile FB group had a five-fold
      increased risk for AKI (adjusted odds ratio 4.98, 95 % confidence interval 1.38
      24.10, p = 0.046) compared to the lowest quartile group, higher postoperative
      peak serum creatinine values (p < 0.001), surgery-related complications (p <
      0.001) and intensive care unit (p < 0.001) and hospital length of stay (p =
      0.048). CONCLUSIONS: Positive FB was associated with increased incidence of AKI.

PMID- 22457093
TI  - Reinterpretation of the electron density at the site of the eighth
      bacteriochlorophyll in the FMO protein from Pelodictyon phaeum.
AB  - The Fenna-Matthews-Olson antenna protein from the green bacterium Pelodictyon
      phaeum mediates the energy transfer from a peripheral antenna complex to the
      membrane-bound reaction center. The three-dimensional structure of this protein
      has been previously modeled using X-ray diffraction to a resolution limit of 2.0
      A, with R (work) and R (free) values of 16.6 and 19.9%, respectively (Larson et
      al., Photosynth Res 107:139-150, 2011). This model shows the protein as
      consisting of beta-sheets surrounding several bacteriochlorophyll cofactors.
      While most of the model clearly matches the electron density maps, in this paper
      we re-examine the electron density for a specific feature, namely the eighth
      bacteriochlorophyll a cofactor. This electron density is now interpreted as
      arising primarily from the end of an otherwise disordered polyethylene glycol
      molecule. Additional electron density is present but the density is weak and
      cannot be unambiguously assigned. The new model has R (work) and R (free) values
      of 16.2 and 19.0%, respectively.

PMID- 22457094
TI  - Genetic and epigenetic mechanisms in thyroid autoimmunity.
AB  - Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's
      thyroiditis, are among the commonest autoimmune disorders, affecting
      approximately 5 % of the population. Epidemiological data support strong genetic
      influences on the development of AITD. Since the identification of HLA-DR3 as a
      major AITD susceptibility gene, there have been significant advances made in our
      understanding of the genetic mechanisms leading to AITD. We have shown that an
      amino acid substitution of alanine or glutamine with arginine at position 74 in
      the HLA-DR peptide binding pocket is a critical factor in the development of
      AITD, and we are continuing to dissect these mechanisms at the molecular level.
      In addition to the MHC class II genes, there are now several other confirmed gene
      loci associated with AITD, including immune-regulatory (CD40, CTLA-4, PTPN22,
      FOXP3, and CD25) and thyroid-specific genes (thyroglobulin and TSHR).
      Mechanistically, it is postulated that susceptibility genes interact with certain
      environmental triggers to induce AITD through epigenetic effects. In this review,
      we summarize some of the recent advances made in our laboratory dissecting the
      genetic-epigenetic interactions underlying AITD. As shown in our recent studies,
      epigenetic modifications offer an attractive mechanistic possibility that can
      provide further insight into the etiology of AITD.

PMID- 22457095
TI  - Characterization of the effect of serum bilirubin concentrations on coronary
      endothelial function via measurement of high-sensitivity C-reactive protein and
      high-density lipoprotein cholesterol.
AB  - Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect
      against atherosclerosis and coronary heart disease (CHD). The goal of this study
      was to characterize the relationship between bilirubin and CHD through
      measurements of bilirubin concentration, coronary endothelial function, and
      markers of oxidative stress, inflammation, and lipid/glucose metabolism. The
      study population consisted of 141 patients without CHD who underwent Doppler flow
      study. Vascular reactivity was examined by intracoronary administration of
      papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire.
      Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde
      modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL
      C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured.
      Homeostasis model assessment insulin resistance index and estimated glomerular
      filtration rate (eGFR) were calculated. Univariate analysis revealed that both
      percent change in coronary blood flow (CBF) and coronary artery diameter induced
      by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05;
      r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh
      correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely
      with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P <
      0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log
      transformed bilirubin was the only independent predictor of percent change in CBF
      in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and
      HDL-C were independent predictors of log-transformed bilirubin. These results
      suggest that a high level of bilirubin is associated with favorable coronary
      endothelial function, which may be mediated via the effect of bilirubin on
      inflammation and HDL-C.

PMID- 22457096
TI  - Complications of cardiac catheterization in adults and children with congenital
      heart disease in the current era.
AB  - The number of adults with congenital heart disease (CHD) requiring diagnostic
      and/or therapeutic cardiac catheterization has been increasing. However, there
      have been few studies on the complications of performing cardiac catheterization
      in adults with CHD. The aim of this study was to determine the incidence of
      complications during congenital cardiac catheterization in both adults and
      pediatric patients. A total of 2134 consecutive cardiac catheterizations
      performed between 2003 and 2008 were prospectively analyzed. Complications were
      graded from 1 to 5 based on severity and these, with >= grade 3 being defined as
      major. During the study period, 576 procedures (393 diagnostic, 90
      interventional, and 93 electrophysiological) were performed in adult patients (>=
      18 years). Complex heart disease was present in 435 of 576 procedures (75.6 %). A
      total of 65 complications (11.3 %) with 13 major complications including 1 death
      (2.3 %) were encountered. The most common complications were arrhythmias. The
      majority of complications were successfully treated or temporary, and all but one
      of the patients were without residua. Of the 1558 pediatric procedures performed
      during the same period, we found a total of 229 complications (14.7 %), of which
      89 (5.7 %) were major complications including 5 deaths. The safety of performing
      cardiac catheterization for adult CHD appears to be similar to that for pediatric
      patients. The complication rates in adults with CHD are low, but not negligible.

PMID- 22457097
TI  - Randomized and double-blind controlled clinical trial of extracorporeal cardiac
      shock wave therapy for coronary heart disease.
AB  - Our aim was to evaluate the safety and effectiveness of extracorporeal cardiac
      shock wave therapy (CSWT) for the patients with coronary heart disease (CHD)
      using a randomized, double-blind, controlled clinical trial design. Twenty-five
      patients with CHD were enrolled in this study. Fourteen of the patients were
      randomized into the CSWT group and 11 into the control group. We applied the CSWT
      procedure to each patient by using nine shock treatments during 3 months, but the
      shock wave (SW) energy was only applied to the patients in the CSWT group and not
      to the patients in the control group. Technetium-99m sestamibi myocardial
      perfusion, fluorine-18 fluorodeoxyglucose myocardial metabolism single-photon
      emission computed tomography (SPECT), and two-dimensional echocardiography were
      performed to identify segments of myocardial ischemia, myocardial viability, and
      ejection fraction before and after CSWT. We also followed the patients to
      evaluate adverse effects. After CSWT, the New York Heart Association class, the
      Canadian Cardiovascular Society angina scale, nitroglycerin dosage, myocardial
      perfusion and myocardial metabolic imaging scores of dual-isotope SPECT in the
      CSWT group were reduced significantly (P = 0.019, 0.027, 0.039, 0.000, 0.001,
      respectively), and the Seattle Angina Questionnaire scale, 6-min walking test,
      and left ventricular ejection fraction were increased significantly (P = 0.021,
      0.024, 0.016, respectively) compared with those before the SW treatment. All of
      the parameters in the control group did not change significantly after the
      treatment (all P > 0.05). No serious adverse effects of CSWT were observed.
      Cardiac shock wave therapy is a safe and effective treatment for CHD patients.

PMID- 22457099
TI  - The frontiers of organ transplantation and cell therapy.
AB  - The biggest problem in the area of organ transplantation is often the mismatch
      between supply and demand. Extrapolating the transplant waiting lists in Spain at
      the end of a year to the global population, more than one million people would be
      able to benefit from a transplant if there were enough available organs and
      adequate infrastructure. The first frontier and the most important is therefore
      the donation of organs. The aim of this chapter is to set out the most notable
      points concerning the various themes (donation, rejection, xenotrasnplants,
      tissue transplantation and stem cells therapy), and describe new avenues to be
      explored: The frontiers that it will be necessary to cross in order to continue
      the progress in saving lives and improving the health of hundreds of thousands of
      people across world.In the last years, embryonic stem cells have become in the
      great hope of many millions of patients across the world. In theory, the
      possibility to have unlimited quantities of these cells, to culture them, and to
      make them differentiate into cells of the liver, nervous system or heart would in
      fact become the ideal solution for the treatment of millions of patients. It is
      quite plausible that what organ transplantation has represented in the 20th
      century, bringing down taboos and saving hundreds of thousands of lives, is going
      to be replaced by stem cell therapy in the 21st Century.

PMID- 22457098
TI  - Pressure applied during surgery alters the biomechanical properties of human
      saphenous vein graft.
AB  - Pressure applied during harvesting of the saphenous vein (SV) graft in coronary
      artery bypass surgery might change its mechanical properties and thereby decrease
      the patency. This study was performed to assess the mechanical properties of the
      SV graft distended manually with different levels of pressure and to determine
      the pressure level that induces changes in its structure and mechanics. Saphenous
      vein graft segments, collected from 36 patients undergoing coronary artery bypass
      surgery, were distended with pressures of either 50-60, 75-100, or 130-150 mmHg.
      Grafts were tested for the stress-strain relationship; the Young's moduli at the
      low- and high-strain regions were calculated, and their structures were examined
      by light and electron microscopy. Pressures of 50-60 mmHg did not influence the
      mechanics of the vein graft, whereas pressures of 75-100 mmHg elevated the
      elastic modulus of the vein at the low-strain region while pressures above 130
      mmHg increased the elastic moduli at both low- and high-strain regions. There was
      a prominent loss of microfibrils at all distending pressure levels. The
      mechanical results suggest that distending pressures above 75 mmHg might play a
      role in graft failure. Furthermore, the absence of microfibrils surrounding
      elastin suggests that application of distending pressures, even as low as 50
      mmHg, can cause degeneration of the elastic fibers following implantation,
      increasing the stiffness of the graft and thus impairing the graft's function
      under its new hemodynamic conditions.

PMID- 22457100
TI  - Organ transplantation in the 21th century.
AB  - Mankind has always been interested in investigating and searching for solutions
      regarding the body deterioration due to factors such as disease, damage caused by
      trauma, toxins or radiation or just the process of ageing. Here, we summarize the
      history of scientific advances in solid organ transplantation, in the areas
      strictly linked to transplantation. The period between the end of the 19th and
      beginning of the 20th century has been called by some authors the "Era of
      allografting". This was a muddled period with many studies and publications on
      very diverse transplants, from Kocher's (Nobel Prize in 1909) who transplanted
      thyroid extracts, to Brown-Sequard who tried to rejuvenate people by using grafts
      of guinea pig testicle extracts. In the midst of the 20th century, Sir Medawar
      pointed out that the rejection of transplant organs by the recipient body was
      mediated by an immunological reaction, which should be modified. Since then,
      there has been an open period of discovery of new immunosuppressive drugs which
      have revolutionised the outcomes of solid organ transplantations. New challenges
      have appeared over the last few years, these efforts have focused on the search
      to extend graft durability and with it recipient patient survival times, as well
      as improve their quality of life.

PMID- 22457101
TI  - Immunology and the challenge of transplantation.
AB  - Transplantation of tissues or organs between individuals who are not genetically
      related often leads to rejection by the recipient. The human genes responsible
      for this process are located on the short arm of the chromosome 6 and are called
      Major Histocompatibility Complex (MHC). Six main loci have been identified in the
      human MHC: HLA-A, HLA-B and HLA-C belong to the HLA class I, while HLA-DP, HLA-DQ
      and HLA-DR belong to HLA class II. The physiological function of MHC molecules is
      to present peptides to the T cells. Indeed, they are integral components of the
      ligands that recognise most T cells, since the receptor of the T cell (TCR) has
      specificity for complexes of foreign antigenic peptides, and self-MHC molecules.
      Thus the proteins of the MHC are responsible for the body being able to
      distinguish between its own and foreign cells, known as self-tolerance and
      consequently are the proteins which determine the evolution of transplants. The
      special case of foreign MHC antigen recognition is known as allorecognition and
      consists of the capacity of T cells to recognise peptide/MHC complexes with which
      they have not been in contact during the process of maturation in the thymus.
      There are two mechanisms of allorecognition, direct and indirect; both can lead
      to rejection of the transplant. Direct recognition prevails during the first few
      weeks or months after transplantation, and is caused by the APCs of the donor.
      These cells start disappearing from the transplanted organ and indirect
      recognition becomes important. There is evidence that the indirect pathway is
      sufficient to mediate both acute and chronic rejection. In this chapter we will
      describe fundamental aspects of the MHC system, as well as, specifically, its
      involvement in the allogenic response of the immune system against organ
      transplants.

PMID- 22457102
TI  - Cellular immunotolerance in the transplant.
AB  - In humans, a state of operational tolerance has been observed in some recipients
      who anecdotally or experimentally abandoned their immunosuppressive treatment.
      Besides, advances in the understanding of the immune response and the continuous
      appearance of new biological molecules have boosted the growing interest in
      transferring the knowledge concerning immune tolerance from experimental models
      to clinical transplantation. Most of the strategies for inducing tolerance target
      the T-lymphocytes, especially T CD4(+) since they play a central role in the
      regulation of the immune response. However, an effective tolerogenic treatment
      must also take into account the role of alloantibody producing B-lymphocytes,
      which have been shown to play a fundamental role in chronic rejection phenomena.
      There are multiple regulation and silencing mechanisms that operate both during
      lymphocyte ontogeny in the bone marrow and thymus (central tolerance) and in the
      periphery (peripheral tolerance). These regulatory mechanisms include the
      destruction of APCs by cytotoxic lymphocytes, suppressive cytokines, and
      activation-induced cell death, among others. However, the mechanism that in
      recent years has come to be attributed the greatest role has been the active
      suppression of the response by T-lymphocytes themselves. These lymphocytes are
      named as regulatory T cells that include Tregs CD4(+)CD25(+), Tr1 cells and Th3.
      The great therapeutic potential of regulatory lymphocyte populations for the
      control of allogeneic rejection is evident and several clinical trials in humans
      have been started to be implemented using populations of both Tregs and Tr1 cells
      for the prevention of allogeneic reactions.

PMID- 22457103
TI  - Immunosuppression in the era of biological agents.
AB  - Immunosuppression is the mayor mechanism to prevent allograft rejection and to
      induce tolerance. Since the first solid organ transplant, the development of safe
      and effective immunosuppressive regimens was a constant over the last decades. A
      lot of immunosuppressants have been discovered, and today the immunosuppressive
      agents are classified in two broad groups: Xenobiotic immunosuppressants and
      biological immunosuppressants. Xenobiotics, like corticoids and calcineurin and
      mTOR inhibitors, mainly interfere with the intracellular molecular mechanisms of
      the various types of cells involved in the immune response and generally these
      immunosuppressants are used early on in the transplantation process to prevent
      rejection as well as in long-term maintenance therapy. On the other hand, target
      molecules of biological immunosuppressants are on the surface of these
      immunological cells and normally in clinical immunosuppressive protocols have
      been used as auxiliary agents of xenobiotics to prevent rejection as well as in
      the treatment of acute rejection. However, these xenobiotics and biological
      agents have multiple side effects; that is why there has been a search for new
      drugs to minimise these side effects and to improve patients' quality of life. In
      this way, new biological agents have been proposed as maintenance
      immunosuppressive agents. The majority of these new immunosuppressive agents are
      polyclonal or monoclonal antibodies and recently the so-called fusion proteins
      may be the start of a new era of biological immunosuppression for maintenance
      regimens.

PMID- 22457104
TI  - Transgenic organs and xenotransplants.
AB  - Advances in immunosuppressive treatments reached in the last decades of the 20th
      century have made solid organ transplantation the treatment of choice for cases
      of irreversible organ failure. However, the availability of human cadaver organs
      is limited and the demand for transplants is still on the rise. Also, there is a
      recognised lack of cells and human tissues for generalised use in transplantation
      for the treatment of diseases that are characterised by failure of specialised
      cells (such as pancreatic cells to cure diabetes). Xenotransplantation, which is
      the transplant of cells, tissues or organs from other species, became the focus
      of attention in the nineteen-nineties as a solution to the lack of organs and
      tissues for transplantation. Previous clinical studies using nonhuman primates
      produced poor outcomes (survival from days to a few months) and confirmed the
      difficulty of obtaining organs from these species. Since then, progress in
      xenotransplantation has been slow and still now various immunological and non
      immunological barriers need to be overcome. These barriers are reviewed in this
      chapter and the various approaches explored to date to overcome them, in
      particular those based on the genetic modification of pigs. Also, cell transplant
      studies such as those of pancreatic islets in monkeys have led to even more
      hopeful results. The range of possibilities offered by this technology will be
      unlimited, making it possible for xenotransplantation to be a clinical reality in
      a not very distant future.

PMID- 22457105
TI  - Cell and tissue therapy in regenerative medicine.
AB  - Cell therapy is one of the most promising future techniques in the medical
      arsenal for the repair of damaged or destroyed tissue. The diseases which cell
      therapy can target are very varied: Hormonal dysfunction, such as diabetes and
      growth hormone deficiency; neurodegenerative diseases, such as Parkinson's,
      Alzheimer's and Huntington's; and cardiovascular lesions, such as myocardial
      infarction, peripheral vascular ischaemia; as well as lesions in the cornea,
      skeletal muscle, skin, joints and bones etc. The objective of cell therapy is to
      restore the lost function rather than produce a new organ, which could cause
      duplicity and undesirable effects. Several resources of cells can be used to
      restore the damaged tissue, such as resident stem cells, multipotent adult
      progenitor cells or embryonic stem cells. Some cell therapies have been
      established and approved for clinical use, such as artificial skin derived from
      keratinocytes, derived from chondrocyte, cells of the corneal limbus or
      pancreatic islet transplantation. These therapies have had good results, although
      the scarcity of the starting material may represent a serious limitation. Other
      therapies under research, using pluripotent stem cells, have been modest so it is
      useful to review the protocols and try to improve the outcomes. In this chapter
      we will review the new advances made in this way.

PMID- 22457106
TI  - Characteristics of adult stem cells.
AB  - Stem cells are characterized by their unlimited ability to divide specifically; a
      stem cell is capable of making an immense number of copies of itself, maintaining
      the same characteristics. Moreover, these cells are able to generate several of
      the cell lineages which make up the body, including cells from the heart, liver,
      kidney, neurons, and muscles. Investigation of the mechanisms through which this
      differentiation occurs, the genes involved and the possibility of increasing the
      efficiency with which stem cells can be isolated and/or characterized are
      currently among the most important fields in biology and biomedicine.To date,
      stems cells have been identified from four different sources: Embryonic stem
      cells (ESC), germinal stem cells, and those derived from embryonic carcinomas
      (teratocarcinomas) and from somatic tissues (somatic stem cells). The latter are
      called adult stem cells (ASC) when they are found in postnatal tissues. We now
      know that there is a great diversity among ASC, with some tissues, such as the
      bone marrow, containing more than one type of ASC. Adult stem cells have several
      characteristics that make them to be the main players in current regenerative
      medicine and are being investigated as potential therapeutic agents for a wide
      variety of diseases. Specifically, HSC and MSC are being assessed in increasing
      numbers of clinical trials.

PMID- 22457107
TI  - Bone marrow transplantation extends its scope.
AB  - The term hematopoietic stem cell transplantation (HSCT) has completely replaced
      the most widespread bone marrow transplantation (BMT). This semantic change is
      based on the fact that not only hematopoietic stem cells with capacity for
      regenerating haematopoiesis and the immune system of the recipient are located in
      the BM. It was later observed that is possible to mobilise these cells into the
      peripheral blood, with the aid of certain cytokines, and then collect them
      through the process of aphaeresis. Moreover, hematopoietic stem cells from
      umbilical cord blood have been used successfully, and their use in on the
      increase. The main objectives of HSCT are, first, to substitute a defective
      haematopoietic system for a healthy one and, secondly, to allow the use of chemo
      and/or radiotherapy treatment at what would otherwise be supralethal doses, re
      establishing haematopoiesis through the administration of haematopoietic
      progenitor cells. The complications of HSCT tend to be the result of the various
      factors including toxicity, release of certain cytokine, immunological processes
      associated with allo-HSCT (especially GVHD) and the effect of immunosuppressive
      drugs, as we discussed below.

PMID- 22457108
TI  - Biology of stem cells: the role of microenvironments.
AB  - From the discovery of the first line of human embryonic stem cells, thousands of
      studies have been published concerning adult stem cells and their possible
      alleged therapeutic potential. However, very little real progress has been made
      in the application of cell therapy to patients. We can conclude that there
      remains a great deal for us to learn about the biology of stem cells, and
      especially, the mechanisms that regulate their differentiation and use under
      conditions of biosafety. In this chapter, we are going to review some of the
      mechanisms that seem to control the biology of stem cells, in particular the
      microenvironments, also called niches, where they house and which exert a strong
      influence over them. The regulation, survival, proliferation and differentiation
      of stem cells is ultimately determined by a combination of factors intrinsic to
      the stem cells themselves and extrinsic signals received from the
      microenvironment. A better understanding of the cellular components of
      microenvironments and their cellular and molecular interactions with the other
      components of the niche, including the stem cells themselves, will be key to make
      progress in this field.

PMID- 22457109
TI  - Mobilization and homing of hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSC) are a population of precursor cells that posses
      the capacity for self-renewal and multilineage differentiation. In the bone
      marrow (BM), HSCs warrant blood cell homeostasis, but at the same time a stable
      pool of functional cells must be constantly maintained. For this, HSCs constitute
      a model in which subpopulations of quiescent and active adult stem cells co-exist
      in the same tissue, in specific microenvironment called stem-cell "niches." These
      microenvironments keep the stem cells at quiescent (osteoblastic niche) for its
      self-renewal and activate the stem cells (vascular niche) for proliferation
      and/or injury repair, maintaining a dynamic balance between self-renewal and
      differentiation. HSC reside in the bone marrow but can be forces into the blood,
      a process termed mobilization used clinically to harvest large number of cells
      for transplantation. At the same time, homing to the BM is necessary to optimize
      cell engraftment. Here, we summarize current understanding of HSC niche
      characteristics, and the physiological and pathological mechanisms that guide HSC
      mobilization both within the BM and to distant niches in the periphery.
      Mobilization and Homing are mirror process depending on an interplay between
      chemokines, chemokine receptors, intracellular signaling, adhesion moleculas and
      proteases. The interaction between SDF-1/CXCL12 and its receptor CXCR4 is
      critical to retain HSCs within the bone marrow. Current mobilization strategies
      used in clinic, mainly G-CSF cytokine, are well tolerated but often produce
      suboptimal number of collected HSCs. Novel agents (AMD3100, stem cell factor,
      GRObetaT.) are being developed to enhance the mobilization to modify the
      signaling into the niche and boost the stem cell harvest, increasing the number
      of HSCs available for the transplant.

PMID- 22457111
TI  - Multipotent mesenchymal stromal cells: clinical applications and cancer modeling.
AB  - The recognition of the therapeutic potential of Multipotent Mesenchymal Stromal
      Cells (MSCs) is one of the most exciting recent advances in cell therapy. In just
      ten years, since the description of the multilineage potential of MSCs by
      Pittenger et al in 1999 until now, MSCs are being used in more than 150 clinical
      trials as therapeutic agents. The potential of these cells for cell-based
      therapies relies on several key properties: (1) their capacity to differentiate
      into several cell lineages; (2) their lack of immunogenicity and their
      immunomodulatory properties; (3) their ex vivo expansion potential; (4) their
      ability to secrete soluble factors which regulate crucial biological functions
      such as proliferation and differentiation over a broad spectrum of target cells;
      and (5) their ability to home to damaged tissues and tumor sites. Based on these
      properties MSCs are being exploited worldwide for a wide range of potential
      clinical applications including cell replacement strategies, treatment of graft
      versus-host disease, autoimmune diseases and rejection after solid organ
      transplantation as well as their use as vehicles to deliver anti-cancer
      therapies. Importantly, the low inherent immunogenicity of MSCs means that they
      could be used not only for autologous but also for allogeneic cell therapies. In
      addition, increasing evidence has revealed a complex relationship between MSCs
      and cancer. Thus, solid evidence has placed MSCs transformed with specific
      mutations as the most likely cell of origin for certain sarcomas, and MSCs have
      been reported to both, inhibit or promote tumor growth depending on yet undefined
      conditions. Here we will thoroughly discuss the different potential clinical
      applications of MSC as well as the role of MSCs on sarcomagenesis and the control
      of tumor growth.

PMID- 22457112
TI  - Neural stem cells and transplantation studies in Parkinson's disease.
AB  - Parkinson's disease (PD), one of the most frequent neurodegenerative disorders,
      is primarily caused by the selective degeneration of specific neuronal
      populations, particularly dopaminergic neurons within the substantia nigra
      projecting to the striatum (nigrostriatal neurons). The current pharmacological
      treatments are efficient in the early stage of the disease but with the
      continuous use of the pro-dopaminergic medication may become less effective and
      cause motor complications. Cell therapy is an emergent alternative therapeutic
      strategy to PD and consists in the replacement of damaged neurons by new cells
      that could help to restore the nigrostriatal pathway. For this purpose, stem
      cells constitute a promising tool that could provide new sources of cells to be
      used for experimental transplantation studies in PD, as well as in other
      neurological disorders. Numerous studies are being made with the use of tissue
      specific neural progenitors obtained from either fetal or adult nervous systems.
      In this chapter we will summarize the numerous preclinical and clinical studies
      performed so far in animal models of the disease as well as in patients and how
      the use of neural stem cells might improve the current cell therapies.

PMID- 22457110
TI  - Great promise of tissue-resident adult stem/progenitor cells in transplantation
      and cancer therapies.
AB  - Recent progress in tissue-resident adult stem/progenitor cell research has
      inspired great interest because these immature cells from your own body can act
      as potential, easily accessible cell sources for cell transplantation in
      regenerative medicine and cancer therapies. The use of adult stem/progenitor
      cells endowed with a high self-renewal ability and multilineage differentiation
      potential, which are able to regenerate all the mature cells in the tissues from
      their origin, offers great promise in replacing non-functioning or lost cells and
      regenerating diseased and damaged tissues. The presence of a small subpopulation
      of adult stem/progenitor cells in most tissues and organs provides the
      possibility of stimulating their in vivo differentiation, or of using their ex
      vivo expanded progenies for cell-replacement and gene therapies with multiple
      applications in humans without a high-risk of graft rejection and major side
      effects. Among the diseases that could be treated by adult stem cell-based
      therapies are hematopoietic and immune disorders, multiple degenerative disorders
      such as Parkinson's and Alzheimer's diseases, Types 1 and 2 diabetes mellitus as
      well as skin, eye, liver, lung, tooth and cardiovascular disorders. In addition,
      a combination of the current cancer treatments with an adjuvant treatment
      consisting of an autologous or allogeneic adult stem/progenitor cell
      transplantation also represents a promising strategy for treating and even curing
      diverse aggressive, metastatic, recurrent and lethal cancers. In this chapter, we
      reviewed the most recent advancements on the characterization of phenotypic and
      functional properties of adult stem/progenitor cell types found in bone marrow,
      heart, brain and other tissues and discussed their therapeutic implications in
      the stem cell-based transplantation therapy.

PMID- 22457113
TI  - Biological impact of human embryonic stem cells.
AB  - Research on human embryonic stem cells (hESCs) and induced pluripotent (iPS) stem
      cells is currently a field of great potential in biomedicine. These cells
      represent a highly valuable tool for developmental biology studies, disease
      models, and drug screening and toxicity. The ultimate goal of hESCs and iPS cell
      research is the treatment of diseases or disorders for which there is currently
      no treatment or existing therapies are only partially effective. Despite the
      disproportionate short-term hopes generated, which are putting too much pressure
      on scientists, the international scientific community is making rapid progress in
      understanding hESCs and iPS cells. Nonetheless, great efforts have to be made to
      provide an answer to still quite basic questions concerning their biology.
      Moreover, translation to clinical applications in cell replacement therapy
      requires prior solution to ethical barriers. The recent development of iPS cells
      has provided a strong alternative to overcome ethical issues concerning hESCs.
      However, an in-depth characterization of their genetic and epigenetic features,
      as well as their differentiation potential still remains to be undertaken. This
      chapter will describe, precisely, what the critical issues are, where scientific
      and ethical barriers stand, and how we are to overcome them. Only then, we shall
      finally discover whether hESCs and iPS cells will allow building reproducible
      disease models, and whether they really are a safe tool, with great potential for
      regenerative medicine.

PMID- 22457114
TI  - Epigenetics of embryonic stem cells.
AB  - Understanding the molecular mechanisms involved in the control of cell
      differentiation during embryonic development is currently one of the main
      objectives of developmental biology. This knowledge will provide a basis for the
      development of new strategies in the field of regenerative medicine, one of the
      most promising weapons to fight many human diseases. Cell differentiation during
      embryonic development is controlled primarily by epigenetic factors, that is,
      mechanisms involved in the regulation of chromatin structure and gene expression.
      Here we describe the best known epigenetic modifications, and pathways, mainly
      focused on DNA methylation and histone modifications, and try to depict the state
      of art in our knowledge about epigenetic regulation of embryonic stem cell
      maintenance and differentiation.

PMID- 22457115
TI  - New tools in regenerative medicine: gene therapy.
AB  - Gene therapy aims to transfer genetic material into cells to provide them with
      new functions. A gene transfer agent has to be safe, capable of expressing the
      desired gene for a sustained period of time in a sufficiently large population of
      cells to produce a biological effect. Identifying a gene transfer tool that meets
      all of these criteria has proven to be a difficult objective. Viral and nonviral
      vectors, in vivo, ex vivo and in situ strategies co-exist at present, although ex
      vivo lenti-or retroviral vectors are presently the most popular.Natural stem
      cells (from embryonic, hematopoietic, mesenchymal, or adult tissues) or induced
      progenitor stem (iPS) cells can be modified by gene therapy for use in
      regenerative medicine. Among them, hematopoietic stem cells have shown clear
      clinical benefit, but iPS cells hold humongous potential with no ethical
      concerns.

PMID- 22457116
TI  - Therapeutic cloning and cellular reprogramming.
AB  - Embryonic stem cells are capable of differentiating into any cell-type present in
      an adult organism, and constitute a renewable source of tissue for regenerative
      therapies. The transplant of allogenic stem cells is challenging due to the risk
      of immune rejection. Nevertheless, somatic cell reprogramming techniques allow
      the generation of isogenic embryonic stem cells, genetically identical to the
      patient. In this chapter we will discuss the cellular reprogramming techniques in
      the context of regenerative therapy and the biological and technical barriers
      that they will need to overcome before clinical use.

PMID- 22457117
TI  - Advances in stem cell therapy.
AB  - Since the beginning of stem cell biology, considerable effort has been focused in
      the translation of scientific insights into new therapies. Cell-based assays
      represent a new strategy for organ and tissue repair in several pathologies.
      Moreover, alternative treatment strategies are urgently needed due to donor organ
      shortage that costs many lives every year and results in lifelong
      immunosuppression. At the moment, only the use of hematopoietic stem cells is
      considered as the standard for the treatment of malignant and genetic bone marrow
      disorders, being all other stem cell applications highly experimental. The
      present chapter tries to summarize some ongoing approaches of stem cell
      regenerative medicine and also introduces recent findings from published studies
      and trials conducted in various tissues such as skeletal muscle, liver and lung.

PMID- 22457118
TI  - Tissue bioengineering and artificial organs.
AB  - The scarcity of organs and tissues for transplant and the need of
      immunosuppressive drugs to avoid rejection constitute two reasons that justify
      organ and tissue production in the laboratory. Tissue engineering based tissues
      (TE) could allow to regenerate the whole organ from a fragment or even to produce
      several organs from an organ donor for grafting purposes. TE is based in: (1) the
      ex vivo expansion of cells, (2) the seeding of these expanded cells in
      tridimensional structures that mimic physiological conditions and, (3) grafting
      the prototype. In order to graft big structures it is necessary that the organ or
      tissue produced "ex vivo" bears a vascular tree to ensure the nutrition of its
      deep layers. At present, no technology has been developed to provide this
      vascular tree to TE derived products. Thus, these tissues must be thin enough to
      acquire nutrients during the first days by diffusion from surrounding tissues.
      This fact constitutes nowadays the greatest limitation of technologies for organ
      development in the laboratory.In this chapter, all these problems and their
      possible solutions are commented. Also, the present status of TE techniques in
      the regeneration of different organ systems is reviewed.

PMID- 22457119
TI  - Benchmarking the thermodynamic analysis of water molecules around a model beta
      sheet.
AB  - Water molecules play a vital role in biological and engineered systems by
      controlling intermolecular interactions in the aqueous phase. Inhomogeneous fluid
      solvation theory provides a method to quantify solvent thermodynamics from
      molecular dynamics or Monte Carlo simulations and provides an insight into
      intermolecular interactions. In this study, simulations of TIP4P-2005 and TIP5P
      Ewald water molecules around a model beta sheet are used to investigate the
      orientational correlations and predicted thermodynamic properties of water
      molecules at a protein surface. This allows the method to be benchmarked and
      provides information about the effect of a protein on the thermodynamics of
      nearby water molecules. The results show that the enthalpy converges with
      relatively little sampling, but the entropy and thus the free energy require
      considerably more sampling to converge. The two water models yield a very similar
      pattern of hydration sites, and these hydration sites have very similar
      thermodynamic properties, despite notable differences in their orientational
      preferences. The results also predict that a protein surface affects the free
      energy of water molecules to a distance of approximately 4.0 A, which is in line
      with previous work. In addition, all hydration sites have a favorable free energy
      with respect to bulk water, but only when the water-water entropy term is
      included. A new technique for calculating this term is presented and its use is
      expected to be very important in accurately calculating solvent thermodynamics
      for quantitative application.

PMID- 22457120
TI  - Lipolytic activity levels and colipase presence in digestive glands of some
      marine animals.
AB  - Studies on the digestive secretions in aquatic animals can elucidate certain
      aspects of their nutritive physiology. The aim of the present study was to
      compare the digestive lipase and phospholipase activities in ten marine species
      belonging to four classes following the taxonomic classification of marine
      organisms. All aquatic digestive tissues tested are equipped with lipase and
      phospholipase activities, assuming the hydrolysis of fat-rich food. The lipolytic
      activities determined in the pancreases of cartilaginous fishes were greater than
      those in bony fishes, molluscs and crustaceans. This finding might be explained
      by the strong digestive utilization of fat-rich macronutrients by these
      carnivorous fishes. A trend of activities and stabilities at different pH and
      temperatures for crude lipases and phospholipases from these aquatic animals
      suggests that the optimum pH and temperature for marine lipases are species
      dependent. Interestingly, the sardine caecal lipase and phospholipase were found
      to be mostly stable in a broad range of acidic pH values. The maximum activities
      of lipolytic enzymes from the hepatopancreases of Hexaplex trunculus (molluscs)
      and Carcinus mediterranus (crustaceans) were found to be 50 and 60  degrees C,
      respectively, whereas the optimal temperature of lipolytic enzymes for the other
      species was classically around 40  degrees C. Thermoactivity of molluscs'
      lipolytic preparations makes them potential candidates in industrial
      applications. Among digestive glands studied, only pancreas (cartilaginous fish)
      contained the classically known colipase. Regarded as the most primitive living
      jawed vertebrates, cartilaginous fishes represented by sharks and rays could be
      considered as the oldest vertebrates possessing a complex digestive system like
      that of mammals.

PMID- 22457123
TI  - Genetic suppression of Galphas protein provides rate control in atrial
      fibrillation.
AB  - Gene therapy-based modulation of atrioventricular (AV) conduction by
      overexpression of a constitutively active inhibitory Galpha(i) protein
      effectively reduced heart rates in atrial fibrillation (AF). However,
      catecholamine stimulation caused an excessive increase in ventricular rate. We
      hypothesized that modest genetic suppression of a stimulatory G protein in the AV
      node would allow persistent rate control in acute AF and would prevent undesired
      heart rate acceleration during beta-adrenergic activation. Atrial fibrillation
      was induced in 12 pigs by atrial burst pacing via an implanted cardiac pacemaker.
      Study animals were then assigned to receive either Ad-siRNA-Galpha(s) gene
      therapy to inactivate Galpha(s) protein or Ad-beta-gal as control. Galpha(s)
      protein inactivation resulted in a 20 % heart rate reduction (P < 0.01). AH and
      HV intervals were prolonged by 37 ms (P < 0.001) and 28 ms (P < 0.001),
      respectively, demonstrating atrioventricular conduction delay. Impairment of left
      ventricular ejection fraction (LVEF) during AF was attenuated by Galpha(s)
      suppression (LVEF 49 %) compared with controls (LVEF 34 %; P = 0.03).
      Isoproterenol application accelerated ventricular heart rate from 233 to 281 bpm
      (P < 0.001) in control animals but did not significantly affect pigs treated with
      Ad-siRNA-Galpha(s) (192 vs. 216 bpm; P = 0.19). In conclusion, genetic inhibition
      of Galpha(s) protein in the AV node reduced heart rate and prevented AF
      associated reduction of cardiac function in a porcine model. Rate control by gene
      therapy may provide an alternative to current pharmacological treatment of AF.

PMID- 22457132
TI  - The continuing confusion in figuring out the surname of a Chinese author: a
      proposed solution.

PMID- 22457133
TI  - Identifying the targets for treatment of liver fibrosis and hepatocellular
      carcinoma from both Western medicine and Chinese medicine.
AB  - Liver fibrosis and hepatocellular carcinoma (HCC) are emerging health problems
      worldwide. Number of death due to HCC was steadily increased during the last
      decade. Although liver fibrosis and HCC have been investigated extensively, there
      are no successful and/or satisfactory therapies especially for patients with HCC.
      From our understanding of both Western medicine and Chinese medicine, it could
      identify the targets in liver fibrosis and HCC for intervention with Chinese
      medicine such as bone morphogenetic protein 4 (BMP-4). BMP-4 expression was
      significantly increased in both liver fibrosis and HCC and saponin class of
      certain Chinese herbs could regulate its expression. Therefore, BMP-4 could be
      one of the targets for treatment of liver fibrosis and HCC from integrative
      medicine.

PMID- 22457134
TI  - The theory of homogeny of liver and kidney in the treatment of kidney and liver
      fibrosis.
AB  - Chronic kidney disease (CKD) and chronic liver disease are both very harmful to
      human health almost all over the world, which lead to the fibrosis of the two
      organs ultimately. Currently, there are few satisfactory therapeutic methods in
      treating the two diseases. Some research works from Chinese medicine and Western
      medicine were done in the area recently, the results showed that kidney and liver
      fibrosis shared similar biological signals and events such as epithelial
      mesenchymal transition (EMT) and transforming growth factor beta 1, the same
      herbal mesenchymal medicine exhibited significantly improving effects on both
      liver fibrosis and kidney fibrosis by involving similar mechanism. This coincides
      with the theory of homogeny of Liver (Gan) and Kidney (Shen) of Chinese medicine.
      It would provides new clues in exploring the treatment of liver fibrosis and
      kidney fibrosis.

PMID- 22457135
TI  - Chinese medicine for treatment of chronic hepatitis B.
AB  - Contemporary Western medicines approved by the U.S. Food and Drug Administration
      (FDA) for the treatment of chronic hepatitis B (CHB), although available in
      China, have high costs, or major side effects and limited effectiveness. Research
      efforts have focused on looking for natural products as alternative medicines
      with low cost and good safety for CHB treatment. Chinese medicine (CM) has
      ancient, time-honored theories about methods of diagnosis and treatment for liver
      diseases. In recent decades, a large number of clinical trials and pre-clinical
      studies, which were performed in China and other countries, indicated that CM has
      potential benefit in several aspects of the treatment of CHB, e.g., anti
      inflammatory, anticancer, antioxidant, immunomodulating, antifibrosis, and
      antiviral. However, there are many concerns regarding the study design and the
      quality of clinical trials. Further larger, stringently designed, double-blind,
      placebo control, randomized clinical trials and long-term follow-up are needed to
      provide conclusive evidence of their efficacy and safety. Components of CM
      deserve further study in pre-clinical models of HBV infection and in clinical
      trials world-wide.

PMID- 22457137
TI  - Study on the effect of Youguiyin () on regulating gene expression profile of the
      rats with femoral head necrosis induced by steroid.
AB  - OBJECTIVE: To observe the regulation of Youguiyin (YGY, ) on the gene expression
      profile of the rat with steroid-induced femoral head necrosis (sFHN), for the
      sake of investigating its molecular mechanism of sFHN prevention and treatment.
      METHODS: All the 30 rats were randomly divided into three groups, the normal
      control group (A), the model control group (B), and the YGY treated group (C), 10
      in each group. After rats in Groups B and C were being made into FHN models with
      steroid injection, they received a daily intragastric administration of saline
      and YGY respectively in equal volume for a total of 6 weeks, while to the
      unmodeled normal rats in Group A, saline was administered instead. The rats were
      sacrificed at the terminal of administration; their mRNA from femoral head tissue
      was extracted and prepared to cDNA probe through inverse transcription for
      detecting gene expression profile by microarray, outcomes of which was passing
      fluorescence quantitative PCR verification, and the differential expressed genes
      were analyzed adopting gene ontology (GO) method. RESULTS: Compared with Group A,
      the numbers of differential genes found in Groups B and C were 190 and 92,
      respectively, but the changing trend in the two groups was opposite, mainly
      manifested as down-regulating in Group B/Group A (GB/GA) and up-regulating in
      Group C/Group B (GC/GB). The analysis showed that these differential genes were
      mainly assigned to cell apoptosis, signal transduction, metabolism, cell
      proliferation and differentiation, cell cycle, blood coagulation, antioxidant
      activity, etc. CONCLUSIONS: sFHN was regulated by various genes; the regulation
      of YGY on expressions of these genes and the intra/extra-cellular signaling
      processes was possibly the molecular mechanism of YGY for preventing/treating
      sFHN. This study gave an explanation to the effectiveness of Chinese medicine in
      preventing/treating FHN from aspects of gene expression and enriched the Chinese
      medicine theory of "Kidney (Shen) governing bones".

PMID- 22457136
TI  - Ping-tang Recipe () improves insulin resistance and attenuates hepatic steatosis
      in high-fat diet-induced obese rats.
AB  - OBJECTIVE: To investigate the therapeutic effects of Ping-tang Recipe (, PTR) on
      high-fat diet (HFD)-induced insulin resistance and non-alcoholic fatty liver
      disease (NAFLD), and to elucidate the underlying mechanisms. METHODS: Forty male
      SD rats were included in the study. Ten rats were fed on normal diet as normal
      control, and thirty rats were fed on HFD for 8 weeks to induce obesity, followed
      with low dose (0.42 g/kg) or high dose (0.84 g/kg) of PTR or vehicle for 8 weeks
      with 10 animals for each group. Glucose metabolism and insulin sensitivity were
      evaluated by oral glucose tolerance test and insulin tolerance test. Hepatic
      steatosis was measured by immunohistochemistry. Liver lipid metabolic genes were
      analyzed by quantitative real-time polymerase chain reaction, while AMP-activated
      protein kinase (AMPK) expression was examined by Western blot. RESULTS: Rats fed
      on HFD developed abdominal obesity, insulin resistance and NAFLD. PTR treatment
      reduced visceral fat (peri-epididymal and peri-renal) accumulation, improved
      glucose metabolism, and attenuated hepatic steatosis. The expressions of the key
      lipolytic regulating genes, including peroxisome proliferators-activated receptor
      gamma co-activator 1alpha (PGC-1alpha), peroxisome proliferator-activated
      receptor gamma (PRAR-gamma) and alpha (PRAR-alpha), were up-regulated (P<0.05 or
      P<0.01), while the expressions of lipogenic genes such as sterol regulatory
      element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and liver fatty
      acid-binding protein (L-FABP) were down-regulated (P<0.05 or P<0.01). In
      addition, PTR activated AMPK and promoted acetyl-CoA carboxylase phosphorylation
      in the liver. CONCLUSIONS: PTR improves insulin resistance and reverse hepatic
      steatosis in the rat model of HFD-induced obesity through promotion of lipolysis
      and reduction of lipogenesis, which involves the AMPK signaling pathway, thus
      representing a new therapeutic intervention for obesity related insulin
      resistance and NAFLD.

PMID- 22457138
TI  - In vitro and in vivo effects of puerarin on promotion of osteoblast bone
      formation.
AB  - OBJECTIVE: To assess the effect of puerarin, a natural flavonoid found in Chinese
      Pueraria Lobata (Wild.) Ohwi, on promotion of new bone formation. METHODS:
      Osteoblasts isolated from calvarial of newborn rats were cultured in vitro in the
      presence of puerarin at various concentrations. The viability of osteoblasts and
      alkaline phosphotase activity and mineral node formation were determined. In
      addition, osteoblasts seeded in the beta-tricaclium phosphate scalfolds as bone
      substitute were implanted in rat dorsal muscles. Half -of the recipient rats
      received intramuscular injection of puerarin at 10 mg/(kg.d) for 7 days.
      Osteogenesis was analyzed by examining the histology after 4 weeks of
      implantation. RESULTS: The viability of osteoblasts treated with puerarin at
      either 40 or 80 MUmol/L was significantly higher than that of the control (P<0.05
      and P<0.01, respectively). Alkaline phosphatase and mineral modules were
      significantly increased in osteoblasts cultured with puerarin at 40 or 80 mol/L
      when compared with that of the untreated cells. The puerarin-treated rats had a
      higher rate of bone formation in the osteoblast implants than the control rats
      (6.35% vs. 1.32%, respectively, P<0.05). CONCLUSION: Puerarin was able to affect
      osteoblast proliferation and differentiation, and promote the new bone formation
      in osteoblast implants.

PMID- 22457139
TI  - Effect of puerarin on the release of interleukin-8 in co-culture of human
      bronchial epithelial cells and neutrophils.
AB  - OBJECTIVE: To investigate the effect of puerarin on interleukin (IL)-8 mRNA
      expression and the protein release in the co-culture of human bronchial
      epithelial (BEAS-2B) cells and human neutrophils. METHODS: BEAS-2B cells and
      neutrophills were cultured separately and co-cultured with puerarin (50, 100, and
      200 MUg/mL) for a predetermined time. Cytokines in culture supernatant were
      evaluated by protein array and IL-8 quantified by enzyme-linked immunosorbent
      assay (ELISA). IL-8 mRNA expression was evaluated by real-time quantitative
      polymerase chain reaction (real-time qPCR). RESULTS: The co-culture of BEAS-2B
      cells and neutrophils exhibited synergistic effects on IL-8 mRNA expression in
      BEAS-2B cells, but not in neutrophils after 12 h incubation (P<0.01), as compared
      with that in BEAS-2B cells or neutrophils alone. IL-8 protein release in the
      culture supernatant was obviously elevated when BEAS-2B cells were co-cultured
      with human neutrophils as compared with that in the supernatant of BEAS-2B cells
      or neutrophils alone after incubated for 2, 6, 12, and 18 h (P<0.01). Treatment
      with puerarin could significantly down-regulate the expression of IL-8 mRNA in
      BEAS-2B cells and IL-8 release in the supernatant of the co-culture of BEAS-2B
      cells and neutrophils (P<0.01). CONCLUSION: Puerarin could exhibit anti
      inflammatory activity by suppressing IL-8 production from the co-culture of human
      bronchial epithelial cells and neutrophils.

PMID- 22457140
TI  - Effect of electro-acupuncture at different acupoints on neuropeptide and
      somatostatin in rat brain with irritable bowel syndrome.
AB  - OBJECTIVE: To compare the regulatory effects of electro-acupuncture (EA) at
      acupoints Zusanli (ST36) and Hegu (LI4) on the visceral hyper-sensitivity in the
      rat model of irritable bowel syndrome (IBS), and to explore the acting targets
      and specialty of acupoints. METHODS: Except 8 rats of the normal control group,
      the rest 32 rats were prepared to set up the IBS models. IBS animal model was
      prepared by enema with acetic acid. Model rats were divided into three groups.
      Except for rats in the model group for control, those in the other two groups
      were treated 20 min by EA on ST36 (EA-ST36) and LI4 (EA-LI4) respectively for 2
      weeks to observe the effect on behavior response of viscera sensitivity. The
      changes of neuropeptide (NPY), the somatostatin (SS) levels in blood and tissues
      of brain and intestine were monitored as well. RESULTS: The volume thresholds for
      abdomen uplifting and back hunching were obviously increased after EA-ST36
      (P<0.05), but showed insignificant change after EA-LI4. NPY contents lowered and
      SS contents increased in model rats; both EA-ST36 and EA-LI4 could raise the
      level of thalamic NPY (P<0.01 and P<0.05, respectively), but showed insignificant
      effects on NPY in colonic tissue. As for SS content, its colonic level could be
      reduced by EA-S36 and EA-LI4 (P<0.01 and P<0.05, respectively), however, its
      blood level was affected only by EA-ST36 (P<0.05). CONCLUSIONS: EA-ST36 or EA-LI4
      could regulate the NPY in thalamus and SS in colonic tissue, the former could
      affect blood level of SS as well. It is deemed that NPY and SS may be the key
      substances for regulating the action of acupuncture in the brain-intestinal axis;
      their different levels could be regarded as an indicator for the functional
      difference between the acupoints.

PMID- 22457141
TI  - Puerarin improve insulin resistance of adipocyte through activating Cb1 binding
      protein path.
AB  - OBJECTIVE: To explore the molecular mechanism of puerarin (Pue) in improving
      insulin resistance through observing its effect on the insulin resistance of 3T3
      Li lipocyte induced by free fatty acid (FFA). METHODS: 3T3-L1 preadipocyte was
      induced by a culture solution containing insulin, isobutyo-menthyl-xanthine, and
      dexamethasone to mature lipocyte, and it was divided into six groups: the control
      group (normal cells), the model group (untreated model cells), and the four drug
      treatment group exposed to dimethyl biguanide (Met group), highdose puerarin
      (PueH group), low-dose puerarin (PueL group), and propylene glycol (PG group),
      respectively. Mature lipocytes in various groups, except those in the normal
      group, were established into insulin resistance model by FFA induction and
      treated respectively with corresponding drugs. Peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) mRNA expressions at the fourth, sixth, and eighth day
      were observed using reverse transcription polymerase chain reaction (RT-PCR);
      glucose transportation in various groups were observed by 2-deoxy-[(3)H]-D
      glucose intake method; mRNA expression of Cb1 binding protein (CAP) was
      determined by RT-PCR; and glucose transporter-4 (Glut-4) transposition was
      detected by immune-fluorescence method. RESULTS: PPAR-gammamRNA expression
      increased gradually, and it showed lower levels at the fourth, sixth, and eighth
      day in all treatment groups than that in the model group. Glucose transportation
      determination showed that the transportation in the model group was 2.23+/-0.63,
      significantly lower than that in the normal group 5.05 +/- 0.66 (P<0.01); as
      compared with the model group, they were significantly higher in the PueH and the
      PueL groups. In addition, the CAP mRNA expression and membranous distribution of
      Glut-4 were higher in the two Pue treated groups than those in the model group,
      respectively. CONCLUSION: Pue could markedly improve the insulin resistance of
      3T3-L1 lipocyte, which is realized possibly by way of inactivating CAP path,
      promoting Glut-4 transposition to cell membrane to increase the transportation of
      glucose.

PMID- 22457142
TI  - The effect of Vaccinium uliginosum on rabbit retinal structure and light-induced
      function damage.
AB  - OBJECTIVE: To study the effect of Vaccinium uliginosum L., (VU) on the
      electroretinogram (ERG) and retinal pathological changes in rabbits after light
      induced damage. METHODS: Twenty-eight Chinchilla rabbits were randomly divided
      into four groups: administration beforehand (A), administration after injury (B),
      light injury without administration (C), and blank (D) groups. After a 4-week
      administration of VU homogenate at 4.8 g/(kg.d) once a day in group A, ERG in
      groups A, B and C were recorded according to the standards set by the
      International Society for Clinical Electrophysiology of Vision (ISCEV). Except
      for group D, the groups were then exposed to strong light. Just after that, group
      A stopped receiving VU treatment and group B started to receive it. Then ERGs in
      all groups were recorded after 1 day, 1 week, and 2 weeks. Throughout the whole
      process groups which were not fed with VU were fed with normal saline. Finally,
      the tissues and structures of all the groups were observed and the thickness of
      the outer nuclear layers (ONL) was measured. RESULTS: (1) After 4-week feeding
      with VU, the latency time of ERG in group A became shorter than those in the
      other groups and the amplitude increased. After being exposed to strong light,
      the latency time lengthened and amplitude decreased in all the injury groups, but
      comparing at each time point, the measured values in group A were better than
      those in group C. With the accumulation of VU, the ERG in group B improved, and
      finally, all of the detected values became better than those in group C. (2)
      Retinae in group D were normal in histology and the layers were in order but
      those in group C became disarranged. The injuries in groups A and B were minor
      compared with those in group C. The thickness of the ONL in group C was
      significantly thinner than in the other groups (P=0.000), and that in groups A
      and B was thicker than that in group C, although thinner than in group D. That in
      group A was thicker than in group B. CONCLUSIONS: VU can relieve the injury to
      rabbit retinae exposed to normal day and night rhythm, alleviate the harm caused
      by light when used beforehand, and repair the light damage to the retina.

PMID- 22457143
TI  - Effect of Sangu Decoction () on metastatic bone destruction in rats with mammary
      cancer.
AB  - OBJECTIVE: To study and evaluate the effect of Sangu Decoction (SGD, ) on the
      bone destruction due to mammary cancer metastasis. METHODS: Metastasis rat
      mammary tumor-1 cells were transplanted into the left hind limb tibia of SD rats
      to establish the bone metastasis of the mammary cancer model. The modeled rats
      were treated with SGD for observing its effect on rats' pain behavior, including
      50% paw withdrawal threshold (50% PWT) after von Frey fiber stimulation, burden
      difference of bilateral feet, and thermal withdrawal latency (TWL), with
      zoledronic acid as the positive control. Moreover, the damage in the tibia sample
      of rats was scored by an iconographic method, and the bone mineral density (BMD)
      as well as the bone mineral content (BMC) were estimated. RESULTS: The model
      established showed characteristics of mixed metastasis, revealing the
      manifestations of tumor development, bone destruction, cancerous pain, etc. In
      the SGD-treated group, 50% PWT was prolonged (8.13 +/- 4.76 vs. 2.30 +/- 2.19),
      and TWL was longer (3.48 +/- 0.62 s vs. 2.89 +/- 0.26 s) than those in the
      control group, respectively (P<0.05 or P<0.01). Iconographic scoring also showed
      improvement of BMD (0.134 +/- 0.009 vs. 0.120 +/- 0.007, P<0.01) and an elevating
      trend of BMC in the SGD-treated group. CONCLUSION: SGD could effectively
      alleviate the cancerous pain of bone metastasis and mitigate the metastasis that
      cause osteolytic destruction of bone.

PMID- 22457144
TI  - Current progress of research on pharmacologic actions of salvianolic acid B.
AB  - As one of the main water-soluble composites of Radix Salviae, salvianolic acid B
      is a phenolic acid ingredient of the Chinese drug, which is rich content in the
      herb and has strong pharmaceutical activity. It is used to treat cardiocerebral
      vascular diseases, antagonize hepatic/renal fibrosis, prevent cancer, and promote
      stem cell proliferation and differentiation. In the researches of its acting
      mechanisms, rather deepened studies have been carried out for its application on
      cardiocerebral vascular diseases, but that for others are rather fewer.

PMID- 22457145
TI  - Intrasynovial flexor tendon repair: a biomechanical study of variations in suture
      application in human cadavera.
AB  - To improve the functional outcomes of intrasynovial tendon suture, prior
      experiments evaluated individual technical modifications used in the repair
      process. Few studies, however, have assessed the combinatorial effects of those
      suture modifications in an integrated biomechanical manner, including a sample
      size sufficient to make definitive observations on repair technique. Two hundred
      fifty-six flexor tendon repairs were performed in human cadavera, and
      biomechanical properties were determined. The effects of five factors for flexor
      tendon repair were tested: core suture caliber (4-0 or 3-0), number of sutures
      crossing the repair site (four- or eight-strand), core suture purchase (0.75 or
      1.2 cm), peripheral suture caliber (6-0 or 5-0), and peripheral suture purchase
      (superficial or 2 mm). Significant factors affecting the properties of the repair
      were the number of core suture strands and the peripheral suture purchase. The
      least significant factors were core suture purchase and peripheral suture
      caliber. The choice of core suture caliber affected the properties of repair
      marginally. Based on these results, we recommend that surgeons continue to focus
      on multi-strand repair methods, as the properties of eight-strand repairs were
      far better than those of four-strand repairs. To resist gap formation and enhance
      repair strength, a peripheral suture with 2 mm purchase is also recommended.
      Finally, since core suture caliber affected some biomechanical properties,
      including the failure mode, a 3-0 suture could be considered, provided that
      future in vivo studies can confirm that gliding properties are not adversely
      influenced.

PMID- 22457147
TI  - Cardiovascular hybrid procedure in severe congenital diaphragmatic hernia with
      significant left heart hypoplasia.
AB  - The authors discuss an early hybrid cardiovascular intervention in a neonate with
      left-sided congenital diaphragmatic hernia and significant left heart hypoplasia.
      The operation included persistent ductus arteriosus stenting and right pulmonary
      artery calibrated banding (3.5 mm) to increase blood flow in the aorta and to
      decrease right ventricle overload and decrease blood pressure and overflow in
      pulmonary circulation. The operation improved the child's general condition and
      gained time for left ventricle growth and restoration of its function.

PMID- 22457148
TI  - Congenitally corrected transposition of the great arteries associated with
      partial anomalous pulmonary venous connection in a quinquagenarian with
      dextrocardia.

PMID- 22457146
TI  - Differential gene expression profile in PBMCs from subjects with AERD and ATA: a
      gene marker for AERD.
AB  - Aspirin-exacerbated respiratory disease (AERD) is associated with severe asthma
      and aspirin can cause asthma to worsen, often in the form of a severe and sudden
      attack. The oral aspirin challenge is the gold standard to confirm the diagnosis
      of AERD, but it is time consuming and produces serious complications in some
      cases. Therefore, more efficient and practical method is needed to predict AERD
      patients. The aim of the present study was to identify AERD-related gene
      expression in peripheral blood mononuclear cells (PBMCs) and examine the
      diagnostic potential of these candidate gene(s) for predicting AERD. To do this,
      RNAs from 24 subjects with AERD and 18 subjects with aspirin-tolerant asthma
      (ATA) were subjected to microarray analysis of ~34,560 genes. In total, 10 genes
      were selected as candidate gene markers by applying p <= 0.001(t test) and >=8
      fold change, and to correct for multiple comparisons, the false discovery rate
      analyses were performed. By applying multiple logistic regression analysis, among
      possible 1,023 models (2(10)-1), a model consisting of CNKSR3, SPTBN2, and IMPACT
      was selected as candidate set, because this set showed the best AUC (0.98) with
      88 % sensitivity and 89 % specificity. For validation, mRNA levels by real-time
      PCR on PBMCs from two population sets in a gene-chip study and another
      replication sample, 20 AERD, 20 ATA, and 8 normal controls, were significantly
      different between groups with 100 % sensitivity and 100 % specificity in each of
      the two population sets. However, IMPACT gene did not differentiate between AERD
      and normal controls. The set of the two genes (CNKSR3 and SPTBN2) showed the best
      AUC (0.96) with 88 % sensitivity and 94 % specificity in a gene-chip study
      sample. In addition, this set showed perfect discriminative power with AUC (1.0,
      100 % sensitivity and 100 % specificity) in each of the two population sets: the
      gene-chip samples and the replication samples. It also showed perfect
      discrimination for AERD from NC (AUC: 1.0) and ATA from NC (AUC: 1.0). In
      conclusion, we developed the two gene markers (CNKSR3 and SPTBN2) of PBMC which
      differentiate between AERD and ATA with a perfect discriminative power. These
      gene markers may be an efficient and practical method for predicting AERD.

PMID- 22457149
TI  - Recombinant factor VIIa while on extracorporeal membrane oxygenator support: a
      word of caution.

PMID- 22457150
TI  - Severe mitral valve regurgitation caused by a swallowed foreign body.

PMID- 22457151
TI  - Assessment of prognostic factors after primary tumor resection in metastatic
      colon cancer patients: a Veteran's Affairs Central Cancer Registry (VACCR)
      analysis, 1995-2008.
AB  - BACKGROUND: Resection of the primary tumor in metastatic colon cancer may occur
      for palliation of bleeding or obstruction despite distant metastases. This study
      evaluates clinicopathologic features that serve as prognostic markers in those
      patients with stage IV colon cancer who undergo resection of their primary tumor.
      METHODS: Retrospective analysis of stage IV colon cancer patients who underwent
      surgical resection of the primary tumor from 1995 to 2008 was done via the
      Veteran's Affairs Central Cancer Registry. Age, Charlson co-morbidity index
      score, extent of metastases, sex, number of lymph nodes examined, lymph node
      ratio (LNR), type of surgery, use of adjuvant chemotherapy, primary tumor site,
      and grade were studied with respect to overall survival by using log-rank and
      Kaplan-Meier analysis. RESULTS: There were 2,625 patients with stage IV colon
      cancer who had primary tumor resection. Age at diagnosis, Charlson co-morbidity
      index score, lymph node ratio, and use of chemotherapy were found to be
      independent predictors of survival by multivariate analysis. CONCLUSION:
      Clinicopathologic factors such as LNR, use of chemotherapy, age, co-morbidities,
      site of primary colon tumor, and number of sites of metastasis are all
      independent predictors of overall survival in patients who undergo primary colon
      tumor resection in the metastatic setting.

PMID- 22457152
TI  - Sample-to-sample torque fluctuations in a system of coaxial randomly charged
      surfaces.
AB  - Polarizable randomly charged dielectric objects have been recently shown to
      exhibit long-range lateral and normal interaction forces even when they are
      effectively net-neutral. These forces stem from an interplay between the quenched
      statistics of random charges and the induced dielectric image charges. This type
      of interaction has recently been evoked to interpret measurements of Casimir
      forces in vacuo, where a precise analysis of such disorder-induced effects
      appears to be necessary. Here we consider the torque acting on a randomly charged
      dielectric surface (or a sphere) mounted on a central axle next to another
      randomly charged surface and show that although the resultant mean torque is
      zero, its sample-to-sample fluctuation exhibits a long-range behavior with the
      separation distance between the juxtaposed surfaces and that, in particular, its
      root-mean-square value scales with the total area of the surfaces. Therefore, the
      disorder-induced torque between two randomly charged surfaces is expected to be
      much more pronounced than the disorder-induced lateral force and may provide an
      effective way to determine possible disorder effects in experiments, in a manner
      that is independent of the usual normal force measurement.

PMID- 22457153
TI  - Simulating self-organized molecular patterns using interaction-site models.
AB  - Molecular building blocks interacting at the nanoscale organize spontaneously
      into stable monolayers that display intriguing long-range ordering motifs on the
      surface of atomic substrates. The patterning process, if appropriately
      controlled, represents a viable route to manufacture practical nanodevices. With
      this goal in mind, we seek to capture the salient features of the self-assembly
      process by means of an interaction-site model. The geometry of the building
      blocks, the symmetry of the underlying substrate, and the strength and range of
      interactions encode the self-assembly process. By means of Monte Carlo
      simulations, we have predicted an ample variety of ordering motifs which nicely
      reproduce the experimental results. Here, we explore in detail the phase behavior
      of the system in terms of the temperature and the lattice constant of the
      underlying substrate.

PMID- 22457157
TI  - Assess before ASCERT.

PMID- 22457158
TI  - TAVI and impaired left ventricular systolic function: a peak around the corner.

PMID- 22457159
TI  - New treatments, new complications...and new solutions.

PMID- 22457162
TI  - The slippery slope of platelet transfusion for intracerebral hemorrhage.

PMID- 22457161
TI  - Age-related differences in treatment strategies and clinical outcomes in
      unselected cohort of patients with ST-segment elevation myocardial infarction
      transferred for primary angioplasty.
AB  - Data concerning the benefits and risks of primary PCI in the elderly patients
      presenting with ST-segment elevation myocardial infarction (STEMI) are limited.
      Thus, the objective of the study was to assess age-dependent differences in the
      treatment and outcomes of STEMI patients transferred for primary PCI. Data were
      gathered on 1,650 consecutive STEMI patients from hospital networks in seven
      countries of Europe from November 2005 to January 2007 (the EUROTRANSFER Registry
      population). Patients <65, 65 to 74, 75 to 84, and >= 85 years of age comprised
      49.3, 27.5, 20.2, and 3 % of the registry population, respectively. Elderly
      patients were higher risk individuals and have experienced longer delays to
      reperfusion than their younger counterparts and were more likely to be treated
      conservatively after coronary angiography. Despite similar frequency of TIMI 3
      flow before PCI, elderly patients were less likely to achieve TIMI 3 flow and ST
      segment resolution >50 % after PCI, and were more likely to have PCI
      complications. The rates of death at 30 days, as well as at 1 year were increased
      with age. In the Cox regression analysis model age was an independent predictor
      of 30-day mortality. A trend toward higher risk of major bleeding requiring
      transfusion was observed. Age was an important determinant of treatment
      strategies selection and clinical outcomes in the group of consecutive STEMI
      patients transferred for primary PCI. Further efforts should be made to reduce
      delays and to optimize treatment of STEMI, regardless of patients' age.

PMID- 22457163
TI  - Continuous 24-hour intraocular pressure monitoring for glaucoma--time for a
      paradigm change.
AB  - Glaucoma is the main cause of irreversible blindness and intraocular pressure
      (IOP) is its only modifiable risk factor. The importance of robust lowering of
      IOP for prevention of glaucoma onset and progression is well established.
      Although IOP is a dynamic parameter with individual circadian rhythms, current
      management usually relies on single IOP measurements during regular clinic hours
      performed a few times a year. Recent technological advances have provided
      clinicians with tools for continuous IOP monitoring during a 24 hour period in an
      ambulatory setting. There are two approaches being investigated. The first is
      permanent IOP monitoring through an implantable sensor and the other is temporary
      monitoring through a contact lens sensor. In this article, we discuss the
      shortcomings of the current gold standard for tonometry (Goldmann Applanation
      Tonometry) and the current experience with the first commercially available
      continuous 24 hour IOP monitoring technology (SENSIMED Triggerfish(r)); a
      telemetric contact lens sensor produced by a Swiss start-up company (Sensimed AG,
      Lausanne, Switzerland). Recent studies suggest that 24 hour continuous monitoring
      of IOP can be integrated into clinical practice and have the potential to
      contribute to the reduction of glaucoma-related vision loss.

PMID- 22457164
TI  - History of the development of pediatric neurosurgery in Ottawa and the Children's
      Hospital of Eastern Ontario (1975-2012).

PMID- 22457165
TI  - Acquired and reversible Chiari-like descent following a single lumbar puncture:
      case report.

PMID- 22457167
TI  - Unmasking of myopotential oversensing by an integrated bipolar defibrillator lead
      following AV node ablation.
AB  - A 73-year-old man with nonischemic cardiomyopathy underwent catheter ablation of
      ventricular tachycardia that had resulted in frequent shocks from his implanted
      cardiac resynchronization therapy defibrillator (CRT-D). Coexisting atrial
      fibrillation required AV node ablation which rendered the patient pacemaker
      dependent. During follow-up, recurrent episodes of dizziness occurred caused by
      inhibition of pacing due to oversensing of pectoral muscle myopotentials.
      Surgical revision was performed and the intraoperative examination revealed an
      intact integrated bipolar defibrillator lead with appropriate connections to the
      CRT-D header. The placement of an additional pace/sense lead completely resolved
      the patient's symptoms and no further myopotential oversensing was recorded.

PMID- 22457166
TI  - Development of a fast LC-MS/MS assay for the determination of deferiprone in
      human plasma and application to pharmacokinetics.
AB  - A fast and accurate liquid chromatography/tandem mass spectrometric (LC-MS/MS)
      assay was first developed and validated for the determination of deferiprone in
      human plasma. The analytes were extracted with acetonitrile from only 50 MUL
      aliquots of human plasma to achieve the protein precipitation. After extraction,
      chromatographic separation of analytes in human plasma was performed using a
      Synergi Fusion-RP 80A column at 30  degrees C. The mobile phase consisted of
      methanol and 0.2% formic acid containing 0.2 mM EDTA (60:40, v/v). The flow rate
      of the mobile phase was 0.8 mL/min. The total run time for each sample analysis
      was 4 min. Detection was performed using electrospray ionization in positive ion
      multiple reaction monitoring mode by monitoring the precursor-to-parent ion
      transitions m/z 140.1 -> 53.1 for deferiprone and m/z 143.1 -> 98.1 for internal
      standard. A linear range was established from 0.1 to 20 ug/mL. The limit of
      detection was determined as 0.05 ug/mL. The validated method was estimated for
      linearity, recovery, stability, precision and accuracy. Intraday and interday
      precisions were 4.3-5.5 and 4.6-7.3%, respectively. The recovery of deferiprone
      was in the range of 80.1-86.8%. The method was successfully applied to a
      pharmacokinetic study of deferiprone in six thalassemia patients.

PMID- 22457168
TI  - Optimal incentives for allocating HIV/AIDS prevention resources among multiple
      populations.
AB  - Many agencies, such as the United Nations Program on HIV/AIDS (UNAIDS), the World
      Health Organization (WHO), the World Bank, the U.S. President's Emergency Plan
      for AIDS Relief (PEPFAR), and the Global Fund to Fight AIDS, Tuberculosis and
      Malaria, provide funding to prevent HIV/AIDS infections worldwide. These funds
      are allocated at multiple levels, resulting in a highly complicated distribution
      process. An oversight agency allocates funds to various national-level decision
      makers who then allocate funds to regional-level decision-makers who in turn
      distribute the monies to local organizations, programs, or risk groups. Simple
      allocation techniques are often preferred by the decision-makers at each
      administrative level, but such methods can lead to sub-optimal allocation of
      funds. Thus, incentives could be provided to decisionmakers in order to encourage
      optimal allocation of HIV/AIDS prevention resources. We formulate an incentive
      based resource allocation model that takes into consideration strategic
      interactions between decision-makers in a multiple-level resource-allocation
      process. We analyze each decision-maker's behavior at the equilibrium and
      summarize the results that characterize the optimal solution to the resource
      allocation problem. Our intended audiences are technical experts, decision
      makers, and policy-makers in governments who can make use of incentives to
      encourage effective decisions regarding HIV/AIDS policy modeling and budget
      allocation at local levels.

PMID- 22457169
TI  - Phlebectomies: to delay or not to delay?

PMID- 22457170
TI  - Interpreting confidence intervals.

PMID- 22457171
TI  - The study on Chan-meditation electrocardiogram by pattern analysis of continuous
      wavelet transform-coefficient map.
AB  - OBJECTIVE: To investigate the effect of Chan-meditation on electrocardiogram
      (ECG) regulated by various respiratory rhythms. METHODS: ECG complexes were
      firstly transformed into continuous wavelet transform (CWT) coefficient map.
      Three schemes were employed in the interpretation of CWT map: the moment
      invariants analysis, the correlation-coefficient analysis of eigenvector derived
      by singular value decomposition (SVD), and the analysis of variance (ANOVA). This
      study involved 17 subjects: 8 experimental subjects with Chan-meditation
      experience and 9 without any Chan-mediation experience as the control subjects in
      the same age range. RESULTS: The results of all 3 different schemes for
      interpreting the CWT map coincidently demonstrated the extraordinary state of
      cardiorespiratory interaction behavior for the experimental subjects breathing at
      higher respiratory rate. According to the ANOVA analysis, the control group
      exhibited statistically significant difference in CWT map of ECG complex at low
      respiratory rates, while experimental group did not. CONCLUSION: This might
      preliminarily suggest that, with slow respiration, Chan-meditation practitioners
      had their cardiac operation more stable than normal people.

PMID- 22457172
TI  - Review of the phytochemical, pharmacological and toxicological properties of
      Alstonia Scholaris Linn. R. Br (Saptaparna).
AB  - The use of ethnornedical information has immensely contributed to health care,
      and scientific studies have shown that the evaluation of traditionally used
      medicines may provide leads towards effective drug discovery. Since antiquity,
      Alstonia scholaris connmonly known as devil's tree has been used for the
      treatment of many human ailments. Literature suggests that Alstonia scholaris is
      useful in treating malaria, abdominal disorders, dyspepsia, leprosy, skin
      diseases, tumors, chronic and foul ulcers, asthma, bronchitis, helminthiasis,
      agalactia, and debility. Preclinical studies have shown that it possesses anti
      microbial, anti-diarrhoeal, anti-plasmodial, anti-oxidant, anti-inflammatory
      hepatoprotective, nootrophic, anti-stress, anti-fertility, immunomodulatory,
      analgesic, anti-ulcer, wound healing, anti-cancer, chemopreventive, radiation
      protection, radiation sensitization, and chemosensitization activities. The
      diverse pharmacological observations are supposed to be due to the presence of
      alkaloids, flavonoids and phenolic acids. The bark and leaf extract when
      administered orally did not induce lethality or adverse affects at the limit
      doses of 2 000 mg/kg body weight. However when administered intraperitoneally at
      high concentrations, the extract showed systemic and developmental toxicities.
      This review addresses the experimentally authenticated facts and also suggests
      the need for research on chemical and pharmacological properties of Alstonia
      scholaris.

PMID- 22457174
TI  - Organ repair and regeneration: an overview.
AB  - A number of organs have the intrinsic ability to regenerate, a distinctive
      feature that varies among organisms. Organ regeneration is a process not fully
      yet understood. However, when its underlying mechanisms are unraveled, it holds
      tremendous therapeutic potential for humans. In this review, we chose to
      summarize the repair and regenerative potential of the following organs and organ
      systems: thymus, adrenal gland, thyroid gland, intestine, lungs, heart, liver,
      blood vessels, germ cells, nervous system, eye tissues, hair cells, kidney and
      bladder, skin, hair follicles, pancreas, bone, and cartilage. For each organ, a
      review of the following is presented: (a) factors, pathways, and cells that are
      involved in the organ's intrinsic regenerative ability, (b) contribution of
      exogenous cells - such as progenitor cells, embryonic stem cells, induced
      pluripotent stem cells, and bone marrow-, adipose- and umbilical cord blood
      derived stem cells - in repairing and regenerating organs in the absence of an
      innate intrinsic regenerative capability, (c) and the progress made in
      engineering bio-artificial scaffolds, tissues, and organs. Organ regeneration is
      a promising therapy that can alleviate humans from diseases that have not been
      yet cured. It is also superior to already existing treatments that utilize
      exogenous sources to substitute for the organ's lost structure and/or
      function(s).

PMID- 22457173
TI  - Jueming Prescription reduces body weight by increasing the mRNA expressions of
      beta3-adrenergic receptor and uncoupling protein-2 in adipose tissue of diet
      induced obese rats.
AB  - OBJECTIVE: To investigate the antiobesity effect of Jueming Prescription (JMP), a
      Chinese herbal medicine formula, and its influence on mRNA expressions of beta3
      adrenergic receptor (beta3-AR) and uncoupling protein-2 (UCP-2) in adipose tissue
      of diet-induced obese rats. METHODS: Fifty male Sprague-Dawley rats were randomly
      divided into the normal control group (n =8) that was on a standard chow diet,
      and the obese model group (n =42) that was on a diet of high fat chow. Two weeks
      after the high fat diet, 29 obese rats in the obese model group were further
      randomly divided into 3 groups: the untreated obese model group (n =9), the
      metformin group (n =10, metformin 300 mg kg-1 day)-1, and the JMP group (n =10,
      JMP 4 g kg-1 day-1). After 8-week treatment, body weight, wet weight of visceral
      fat, and percentage of body fat (PBF) were measured. The levels of fasting blood
      glucose, serum lipids, and insulin were assessed, and insulin sensitivity index
      (ISI) was calculated. The adipose tissue section was stained with hematoxylin
      Eosin, and the cellular diameter and quantity of adipocytes were evaluated by
      light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the peri-renal
      fat tissue were determined by real-time reverse transcription polymerase chain
      reaction (RT-PCR). RESULTS: Compared with the obese model group, treatment with
      JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF,
      and diameter of adipocytes, and significantly higher level of high-density
      lipoprotein cholesterol, ISI (all P<0.01), JMP increased the mRNA expressions of
      beta3-AR and UCP-2 from perirenal fat tissue (P <0.05, P<0.01). CONCLUSIONS: JMP
      could reduce body weight and adipocyte size; and the effect was associated with
      the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and
      improvement of insulin sensitivity.

PMID- 22457175
TI  - Developmental engineering the kidney: leveraging principles of morphogenesis for
      renal regeneration.
AB  - Multiple methodological approaches are currently under active development for
      application in tissue engineering and regenerative medicine of tubular and solid
      organs. Most recently, developmental engineering (TE/RM), or the leveraging of
      embryonic and morphological paradigms to recapitulate aspects of organ
      development, has been proposed as a strategy for the sequential, iterative de
      novo assembly of tissues and organs as discrete developmental modules ex vivo,
      prior to implantation in vivo. In this article, we focus on the kidney to
      highlight in detail how principles of developmental biology are impacting
      approaches to TE of this complex solid organ. Ultimately, such methodologies may
      facilitate the establishment of clinically relevant therapeutic strategies for
      regeneration of renal structure and function, greatly impacting treatment
      regimens for chronic kidney disease.

PMID- 22457176
TI  - Animal models for basic and translational research in reconstructive
      transplantation.
AB  - Reconstructive transplantation represents a bona fide option for select patients
      with devastating tissue loss, which could better restore the appearance, anatomy,
      and function than any other conventional treatment currently available. Despite
      favorable outcomes, broad clinical application of reconstructive transplantation
      is limited by the potential side effects of chronic multidrug immunosuppression.
      Thus, any reconstructive measures to improve these non-life-threatening
      conditions must address a delicate balance of risks and benefits. Today, several
      exciting novel therapeutic strategies, such as the implementation of cellular
      therapies including bone marrow or stem cells that integrate the concepts of
      immune regulation with those of nerve regeneration, are on the horizon. The
      development of reliable and reproducible small and large animal models is
      essential for the study of the unique immunological and biological aspects of
      vascularized composite allografts and to translate such novel immunoregulatory
      and tolerance-inducing strategies and therapeutic concepts from the bench to
      bedside. This review provides an overview of the multitude of small and large
      animal models that have been particularly designed for basic and translational
      research related to reconstructive transplantation.

PMID- 22457177
TI  - Deer antler regeneration: a stem cell-based epimorphic process.
AB  - Full regeneration of deer antlers, a bona fide epimorphic process in mammals, is
      in defiance of the general rule of nature. Revealing the mechanism underlying
      this unique exception would place us in a better position to promote organ
      regeneration in humans. Antler regeneration takes place in yearly cycles from its
      pedicle, a permanent protuberance on the frontal bone. Both growing antlers and
      pedicles consist of internal (cartilage and bone) and external components (skin,
      blood vessels, and nerves). Recent studies have demonstrated that the
      regeneration of both internal and external components relies on the presence of
      pedicle periosteum (PP). PP cells express key embryonic stem cell markers (Oct4,
      Nanog, and SOX2) and are multipotent, so are termed antler stem cells. Now it is
      clear that proliferation and differentiation of PP cells directly forms internal
      antler components; however, how PP initiates and maintains the regeneration of
      external antler components is thus far not known. Based on the direct as well as
      indirect evidence that is presented in this review, I put forward the following
      hypothesis to address this issue. The full regenerative ability of external
      antler tissue components is achieved through PP-derived chemical induction and PP
      derived mechanical stimulation: the former triggers the regeneration of these
      external components, whereas the latter drives their rapid elongation. Eventual
      identification of the putative PP-derived chemical factors would open up a new
      avenue for devising effective therapies for lesions involving each of these
      tissue components, be they traumatic, degenerative, or linked to developmental
      (genetic) anomalies.

PMID- 22457180
TI  - The potential of adipose-derived stem cells in craniofacial repair and
      regeneration.
AB  - The recent identification of a mesenchymal stem cell population in adipose tissue
      has led to an abundance of research focused on the regenerative properties of
      these cells. As such, adipose-derived stem cells (ASCs) and potential therapies
      in craniofacial regeneration have been widely studied. This review will discuss
      the identification and potential of ASCs, and specifically, preclinical and
      clinical studies using ASCs in craniofacial repair. Studies involving ASCs in the
      repair of defects caused by craniosynostosis and Treacher Collins syndrome will
      be discussed. A comprehensive review of the literature will be presented,
      focusing on fat grafting and biomaterials-based approaches that include ASCs for
      craniofacial regeneration.

PMID- 22457181
TI  - Pluripotent stem cell-based heart regeneration: from the developmental and
      immunological perspectives.
AB  - Heart diseases such as myocardial infarction cause massive loss of
      cardiomyocytes, but the human heart lacks the innate ability to regenerate. In
      the adult mammalian heart, a resident progenitor cell population, termed
      epicardial progenitors, has been identified and reported to stay quiescent under
      uninjured conditions; however, myocardial infarction induces their proliferation
      and de novo differentiation into cardiac cells. It is conceivable to develop
      novel therapeutic approaches for myocardial repair by targeting such expandable
      sources of cardiac progenitors, thereby giving rise to new muscle and
      vasculatures. Human pluripotent stem cells such as embryonic stem cells and
      induced pluripotent stem cells can self-renew and differentiate into the three
      major cell types of the heart, namely cardiomyocytes, smooth muscle, and
      endothelial cells. In this review, we describe our current knowledge of the
      therapeutic potential and challenges associated with the use of pluripotent stem
      cell and progenitor biology in cell therapy. An emphasis is placed on the
      contribution of paracrine factors in the growth of myocardium and
      neovascularization as well as the role of immunogenicity in cell survival and
      engraftment.

PMID- 22457178
TI  - Using polymeric materials to control stem cell behavior for tissue regeneration.
AB  - Patients with organ failure often suffer from increased morbidity and decreased
      quality of life. Current strategies of treating organ failure have limitations,
      including shortage of donor organs, low efficiency of grafts, and immunological
      problems. Tissue engineering emerged about two decades ago as a strategy to
      restore organ function with a living, functional engineered substitute. However,
      the ability to engineer a functional organ is limited by a limited understanding
      of the interactions between materials and cells that are required to yield
      functional tissue equivalents. Polymeric materials are one of the most promising
      classes of materials for use in tissue engineering, due to their
      biodegradability, flexibility in processing and property design, and the
      potential to use polymer properties to control cell function. Stem cells offer
      potential in tissue engineering because of their unique capacity to self-renew
      and differentiate into neurogenic, osteogenic, chondrogenic, and myogenic
      lineages under appropriate stimuli from extracellular components. This review
      examines recent advances in stem cell-polymer interactions for tissue
      regeneration, specifically highlighting control of polymer properties to direct
      adhesion, proliferation, and differentiation of stem cells, and how biomaterials
      can be designed to provide some of the stimuli to cells that the natural
      extracellular matrix does.

PMID- 22457182
TI  - Giant saphenous vein graft pseudoaneurysm: treatment with a vascular occlusion
      device.
AB  - We report the case of a 74-year old male who was evaluated for progressively
      enlarging right heart border on serial chest radiographs. Computed tomography of
      the chest revealed a pseudoaneurysm arising from the saphenous vein graft (SVG)
      to the posterior descending artery with mass effect on the right atrium. Coronary
      angiography showed severely compromised distal flow and an angiographically small
      territory at risk. Using a minimally invasive, catheter-based approach, an
      Amplatzer Vascular Plug II occlusion device was utilized successfully for
      embolizing the SVG pseudoaneurysm.

PMID- 22457179
TI  - Biological approaches to improve skeletal muscle healing after injury and
      disease.
AB  - Skeletal muscle injury and repair are complex processes, including well
      coordinated steps of degeneration, inflammation, regeneration, and fibrosis. We
      have reviewed the recent literature including studies by our group that describe
      how to modulate the processes of skeletal muscle repair and regeneration.
      Antiinflammatory drugs that target cyclooxygenase-2 were found to hamper the
      skeletal muscle repair process. Muscle regeneration phase can be aided by growth
      factors, including insulin-like growth factor-1 and nerve growth factor, but
      these factors are typically short-lived, and thus more effective methods of
      delivery are needed. Skeletal muscle damage caused by traumatic injury or genetic
      diseases can benefit from cell therapy; however, the majority of transplanted
      muscle cells (myoblasts) are unable to survive the immune response and hypoxic
      conditions. Our group has isolated neonatal skeletal muscle derived stem cells
      (MDSCs) that appear to repair muscle tissue in a more effective manner than
      myoblasts, most likely due to their better resistance to oxidative stress.
      Enhancing antioxidant levels of MDSCs led to improved regenerative potential. It
      is becoming increasingly clear that stem cells tissue repair by direct
      differentiation and paracrine effects leading to neovascularization of injured
      site and chemoattraction of host cells. The factors invoked in paracrine action
      are still under investigation. Our group has found that angiotensin II receptor
      blocker (losartan) significantly reduces fibrotic tissue formation and improves
      repair of murine injured muscle. Based on these data, we have conducted a case
      study on two hamstring injury patients and found that losartan treatment was well
      tolerated and possibly improved recovery time. We believe this medication holds
      great promise to optimize muscle repair in humans.

PMID- 22457183
TI  - Stage I non-small cell lung cancer: the presence of the lymphocyte-specific
      protein tyrosin kinase in the tumour infiltrate is associated with a better long
      term prognosis.
AB  - We studied the expression in the tumour infiltrate of a T-cell activation marker,
      the lymphocyte-specific protein tyrosin kinase (LCK), to assess if it could be
      associated with a better prognostic outcome in early stage non-small cell lung
      cancer (NSCLC) patients. This retrospective study included 25 patients undergoing
      lobectomy with systematic hilo-mediastinal lymphadenectomy for pathological stage
      I NSCLC between July 2003 and June 2005. The presence of LCK was detected in the
      tumour infiltrate by immunohistochemistry on the specimens of all patients. No
      patient received adjuvant therapy. Twelve patients resulted LCK-positive and 13
      LCK-negative. The distribution of patients according to the T-stage was similar
      between the LCK-positive group (1 T1a, 5 T1b, 6 T2a) and the LCK-negative group
      (1 T1a, 5 T1b, 7 T2a). Median overall survival (OS) time was not reached in the
      LCK-positive group and 30 months in the LCK-negative group (P = 0.01). OS was
      longer than 40 months in 75% of the LCK-positive patients and in 31% of the LCK
      negative patients (P = 0.01). Median time to relapse (TTR) was significantly
      longer in LCK-positive patients than in LCK-negative patients (not reached vs. 25
      months; P < 0.001). In conclusion, LCK-positive tumour infiltrate has been found
      to be associated with a significantly longer OS and TTR in patients with
      radically resected stage I NSCLC.

PMID- 22457184
TI  - A successful third resection-anastomosis in a tracheal restenosis.
AB  - Reoperation due to recurrence after tracheal resection and reconstruction still
      seems challenging. Although recurrence may lead to serious morbidity, an
      appropriate surgical technique plays a significant role in the cure of these
      patients. We report our experience of a patient who successfully underwent a
      third resection and anastomosis of the trachea. We believe that the number of
      previous operations is not a contraindication by itself against reoperating on a
      patient with restenosis. Also the success rate might be acceptably high if a
      sufficiently healthy tracheal length remains.

PMID- 22457185
TI  - Intravital microscopy to study myocardial engraftment.
AB  - Tissue engineering and stem cell transplantation are promising novel therapies
      for myocardial repair. A major barrier to cell survival after transplantation
      involves inadequate vascularization. Continuous observation of cardiac tissue
      engraftment and angiogenesis could help understand these processes and allow for
      identification of the optimal conditions for these therapeutic interventions. We
      investigated the ability of a skin-fold chamber model to allow for engraftment of
      differentiated myocardial tissue in mice. Neonatal atrial and ventricular tissues
      were implanted in the in vivo chambers. All myocardial implants had a high rate
      of engraftment (86-95%). Tissue engraftment was preceded by a 'bleeding phase' in
      both the atrial and ventricular implants. This occurred earlier in ventricular
      compared with atrial implants. Spontaneous contractions were observed after an
      average of 13 days after implantation in all chambers but occurred earlier in
      ventricular compared with atrial implants. The host cells surrounded the
      myocardial implants circumferentially, but have limited infiltration into these
      grafts. This is the first report of successful ectopic engraftment of
      differentiated myocardium using a skin-fold chamber. This model is invaluable for
      real-time observation of early angiogenesis and tissue growth during in vivo
      myocardial engineering and myocardial regeneration.

PMID- 22457186
TI  - Systemic oxygen transport derived by using continuous measured oxygen consumption
      after the Norwood procedure-an interim review.
AB  - The balance between systemic O(2)consumption (VO(2)) and O(2)delivery (DO(2)) is
      impaired in children after cardiopulmonary bypass surgery, with decreased
      DO(2)and increased VO(2). The major goal, and the major challenge, of
      postoperative management has been to match DO(2)to VO(2)in order to sustain
      cellular metabolism, particularly in neonates after the Norwood procedure. While
      much effort has been put into augmenting cardiac output and DO(2), VO(2)remains
      largely ignored. Respiratory mass spectrometry allows the precise and continuous
      measurement of VO(2). Measured VO(2), using the direct Fick principle, allows for
      the calculation of each element of systemic O(2)transport in the complex Norwood
      circulation. The actual measurements of O(2)transport have allowed us, in the
      past five years or so, to extensively investigate the Norwood physiology in terms
      of the VO(2)-DO(2)relationship and the factors affecting it in clinical
      treatments. Therefore, the first objective of this article is to introduce the
      technique of respiratory mass spectrometry and its adaption to measure
      VO(2)across paediatric ventilators with continuous flow. The second objective is
      to give an interim review of the main findings in our studies on systemic
      O(2)transport in 17 neonates in the first 72 h after the Norwood procedure. These
      findings include the profiles of systemic O(2)transport, the important
      contribution of VO(2)to the impaired balance of O(2)transport and the complex
      effects of some routine clinical treatments on the VO(2)-DO(2)relationship
      (including catecholamines, PaCO(2), Mg(2+)and hyperglycaemia, as well as patient
      specific anatomical variations). The influence of systemic O(2)transport on
      cerebral oxygenation is also introduced. This information may help us to refine
      postoperative management in neonates after the Norwood procedure. Our initial
      studies mark the end of the beginning, but much is yet explored. Ultimately, the
      resultant improved systemic and regional O(2)transport in the early postoperative
      period may have an important impact on long-term outcomes, thereby improving the
      quality of life for these vulnerable children.

PMID- 22457187
TI  - What do you do with the antiplatelet agents in patients with drug eluting stents
      who then receive a mechanical valve?
AB  - Dual antiplatelet therapy (DAT) with aspirin and clopidogrel is a cornerstone of
      treatment during and after percutaneous coronary interventions with drug-eluting
      stent (DES) implantation. Oral anticoagulation (OAC) is the recommended treatment
      for patients with mechanical heart valves. When patients with DES need a
      mechanical heart valve or vice versa, we face the difficult choice of their
      antithrombotic therapy. Different institutions empirically follow a combination
      of OAC and single or DAT, the so-called triple antithrombotic therapy (TT) aiming
      to find the best balance between the thrombotic and bleeding risk for this subset
      of patients. A best evidence topic in cardiac surgery was written according to a
      structured protocol. The question addressed was whether there is an optimal
      antithrombotic management for patients with DES undergoing mechanical heart valve
      or vice versa. Altogether, more than 148 papers were found using the reported
      search, of which 16 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.
      We conclude that DES implantation in patients who could potentially need valve
      surgery in the future should be discouraged and bare-metal stent or an aortic
      bioprosthesis preferred. However, in high-risk patients with DES, the
      recommendation is to postpone elective surgery for 1 year and, if surgery cannot
      be deferred, continue aspirin during the perioperative period. Moreover, when OAC
      is given in combination with clopidogrel and/or low-dose aspirin, the target INR
      should be 2.0-2.5 (Class IIb, level of evidence C). As per the long-term
      management, antithrombotic management with DAT alone in mechanical aortic valve
      replacement might be possible, but there is not enough evidence to support it.
      The available evidence suggests that triple anticoagulation (OAC + DAT) is
      associated with the best clinical outcome compared with all the other possible
      strategies. The duration of TT should be 3 months after sirolimus DES
      implantation, and 6 months after paclitaxel DES implantation, followed by long
      term therapy with OAC plus clopidogrel or aspirin with either PPIs, or H2
      receptor antagonists (Class IIa Level of Evidence C).

PMID- 22457188
TI  - Tricuspid regurgitation after successful mitral valve surgery.
AB  - The tricuspid valve (TV) is inseparably connected with the mitral valve (MV) in
      terms of function. Any pathophysiological condition concerning the MV is
      potentially a threat for the normal function of the TV as well. One of the most
      challenging cases is functional tricuspid regurgitation (TR) after surgical MV
      correction. In the past, TR was considered to progressively revert with time
      after left-sided valve restoration. Nevertheless, more recent studies showed that
      TR could develop and evolve postoperatively over time, as well as being closely
      associated with a poorer prognosis in terms of morbidity and mortality. Pressure
      and volume overload are usually the underlying pathophysiological mechanisms;
      structural alterations, like tricuspid annulus dilatation, increased leaflet
      tethering and right ventricular remodelling are almost always present when
      regurgitation develops. The most important risk factors associated with a higher
      probability of late TR development involve the elderly, female gender, larger
      left atrial size, atrial fibrillation, right chamber dilatation, higher pulmonary
      artery systolic pressures, longer times from the onset of MV disease to surgery,
      history of rheumatic heart disease, ischaemic heart disease and prosthetic valve
      malfunction. The time of TR manifestation can be up to 10 years or more after an
      MV surgery. Echocardiography, including the novel 3D Echo techniques, is crucial
      in the early diagnosis and prognosis of future TV disease development.
      Appropriate surgical technique and timing still need to be clarified.

PMID- 22457189
TI  - Is a tricuspid annuloplasty ring significantly better than a De Vega's
      annuloplasty stitch when repairing severe tricuspid regurgitation?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether tricuspid valve (TV) repair with an
      annuloplasty ring leads to an improved outcome over a conventional suture
      annuloplasty for patients with severe tricuspid incompetence. Altogether, 306
      papers were found using the reported search, of which 14 presented the best
      evidence to answer the clinical question. The author, journal, date and country
      of publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of these papers are tabulated. We found seven studies supporting
      the use of ring annuloplasty over De Vega's suture annuloplasty. Five studies
      found no significant difference in outcome between the two techniques. We found
      only two studies supporting the use of De Vega's suture annuloplasty over ring
      annuloplasty. Therefore, most of the tabulated studies show good evidence in
      support of ring annuloplasty compared with De Vega's suture repair for treatment
      of moderate to severe TV regurgitation. One cohort study identified a 20.4%
      postoperative failure rate for tricuspid regurgitation (TR) repair and concluded
      non-application of ring as a predictor for reoperation. One cohort study with a
      mean follow-up of 17 months reported success rates as high as 97% with ring
      annuloplasty for TV regurgitation. One large cohort study of 2277 patients with
      TR who had undergone repair reported a sustained reduction in TR and the rate of
      recurrence in a 5-year echocardiographic follow-up. One cohort study of 129
      patients concluded that ring annuloplasty has the lowest rate of recurrence
      compared with De Vega's suture repair. An old randomized controlled trial (RCT)
      on the subject also reported a similar result to the mentioned studies. In
      contrast, we reviewed one recent study and four older studies and found no
      significant difference between the two techniques. We reviewed one study that
      reported De Vega's suture repair as a superior technique to ring annuloplasty. We
      conclude that there is good evidence supporting ring annuloplasty over
      conventional De Vega's suture annuloplasty.

PMID- 22457190
TI  - Radiotherapy-related axillary arteriopathy.
AB  - Treatment of breast cancer involves surgery, then perhaps radiation, hormonal or
      chemotherapy. Radiation-induced arterial injury is a well-known entity that
      represents a rare cause of arterial occlusion. We present the case of a 76-year
      old woman who complained of a severe intermittent claudication of the right upper
      limb. Twenty years before, she underwent a right-sided radical mastectomy
      followed by intense radiation therapy for several weeks. The patient was found to
      suffer of a radiotherapy-related axillary artery thrombosis and was successfully
      treated by angioplasty and stenting.

PMID- 22457191
TI  - Serosurvey and molecular detection of Crimean-Congo hemorrhagic fever virus
      (CCHFV) in northern Turkey.
AB  - In this study, the hard ticks, whole blood and serum samples collected from small
      ruminants (sheep and goat) in middle Black Sea region of Turkey where Crimean
      Congo hemorrhagic fever (CCHF) human cases were observed in the past years were
      surveyed for the presence of RNA and specific IgG antibodies from CCFH virus
      (CCHFV). CCHFV RNA was found in 30 of 255 tick pools (11.76%) and nine of 105
      (8.57%) leucocyte samples. No CCHFV genomic RNA was detected from animals in
      Yildizeli and Vezirkopru. However, CCHFV RNA was found from animals in Gerze and
      Resadiye. Seventy-eight of 105 goat and sheep blood serum samples tested were
      antibody-positive for CCHFV by enzyme-linked immunosorbent assay (ELISA) (goat:
      42/63; sheep: 36/42). Viral RNA was detected from tick samples in all of four
      provinces. Positivity rates for the provinces varied and were as follows: Gerze
      13.04%, Resadiye 35.41%, Vezirkopru 1.61% and Yildizeli 6.06%. CCHFV genomic RNA
      was detected in four of seven tick species tested. These results suggest that
      these hard ticks may act as a reservoir for CCHFV in northern Turkey.

PMID- 22457192
TI  - Indeterminate pulmonary nodules in rectal cancer: a recommendation for follow-up
      guidelines.
AB  - BACKGROUND: Incidental visualization of indeterminate pulmonary nodules is
      considered a clinical dilemma. METHODS: We identified patients for inclusion in
      this study by searching for the term "indeterminate nodules" in the radiology
      database of rectal cancer patients who underwent surgery. Patients with definite
      metastatic disease were excluded. RESULTS: In total, 224 patients underwent chest
      computerized tomography (CT) and 59 of these patients had indeterminate pulmonary
      nodules detected more than twice by CT scan. Six patients (10.2%) were confirmed
      to have metastatic lesions on follow-up evaluation. Pulmonary nodule size
      (P=0.028), pathologic N status (P=0.049), positive nodal status (P=0.036) and the
      number of positive lymph nodes (P=0.033) were significant risk factors for
      pulmonary metastasis. In the pulmonary metastasis group, the patients who had
      received adjuvant oxaliplatin-based (FOLFOX4) chemotherapy had longer intervals
      to developing metastasis compared to patients who had not received it.
      CONCLUSIONS: It is not necessary to perform excessive surveillance routinely for
      all rectal cancer patients who have indeterminate pulmonary lesions. Intensive
      follow-up chest CT or other invasive diagnostic modalities should be considered
      only in patients with pulmonary nodules larger than 5.7 mm or positive nodal
      status. In addition, patients receiving adjuvant FOLFOX4 chemotherapy should be
      followed-up for longer periods.

PMID- 22457198
TI  - Inhibition of sclerostin by systemic treatment with sclerostin antibody enhances
      healing of proximal tibial defects in ovariectomized rats.
AB  - Recent studies suggest a possible role for inhibitors of sclerostin such as
      sclerostin antibody (Scl-Ab) as an anabolic treatment for osteoporosis. Since Scl
      Ab has also been shown to potentiate bone repair, we examined the effect of Scl
      Ab treatment in a metaphyseal defect repair model in ovariectomized (OVX) rats.
      Four weeks after OVX or sham surgery, 3 mm circular defects were created
      bilaterally in the proximal tibia of all rats. After defect surgery, Saline or 25
      mg/kg Scl-Ab was administered twice weekly for 3 weeks. Of note, healing was
      advanced in the 1-week post-defect surgery in OVX controls over Sham controls,
      with increases in bone volume and fluorochrome labeling observed. However, by
      week 2, OVX controls fell significantly behind in the repair response compared
      with Sham controls. Scl-Ab treatment significantly increased bone volume in the
      defect in OVX rats over the 3-week time course as examined by either microCT or
      histology. Significant increases in bone formation via fluorochrome labeling of
      the new bone were observed with Scl-Ab treatment, while osteoclast parameters
      were not different. With its powerful anabolic potential, bone-specific activity,
      and potential for low dosing frequency, Scl-Ab treatment could provide enhanced
      bone repair, particularly in situations of compromised bone repair such as
      osteoporotic bone.

PMID- 22457199
TI  - Transmembrane collagen XVII is a novel component of the glomerular filtration
      barrier.
AB  - The kidney filtration barrier consists of the capillary endothelium, the
      glomerular basement membrane and the slit diaphragm localized between foot
      processes of neighbouring podocytes. We report that collagen XVII, a
      transmembrane molecule known to be required for epithelial adhesion, is expressed
      in podocytes of normal human and mouse kidneys and in endothelial cells of the
      glomerular filtration barrier. Immunoelectron microscopy has revealed that
      collagen XVII is localized in foot processes of podocytes and in the glomerular
      basement membrane. Its role in kidney has been analysed in knockout mice, which
      survive to birth but have high neonatal mortality and skin blistering and
      structural abnormalities in their glomeruli. Morphometric analysis has shown
      increases in glomerular volume fraction and surface densities of knockout
      kidneys, indicating an increased glomerular amount in the cortex. Collagen XVII
      deficiency causes effacement of podocyte foot processes; however, major slit
      diaphragm disruptions have not been detected. The glomerular basement membrane is
      split in areas in which glomerular and endothelial basement membranes meet.
      Differences in the expression of collagen IV, integrins alpha3 or beta1, laminin
      alpha5 and nephrin have not been observed in mutant mice compared with controls.
      We propose that collagen XVII has a function in the attachment of podocyte foot
      processes to the glomerular basement membrane. It probably contributes to
      podocyte maturation and might have a role in glomerular filtration.

PMID- 22457200
TI  - Why and how to support screening strategies to prevent sudden death in athletes.
AB  - Sudden death in athletes occurs because of the existence of hidden cardiovascular
      disorders which, during effort, may jeopardize the electrical stability of the
      heart, triggering ventricular tachycardia and/or fibrillation. Apart from rare
      conditions of ion channel diseases in the setting of a structurally normal heart,
      in which the disorder may be easily diagnosed on basal or stress test ECG,
      cardiac abnormalities at risk of causing sudden death may affect the aorta
      (Marfan syndrome), the coronary arteries (congenital coronary artery anomalies,
      premature coronary atherosclerosis), the myocardium (hypertrophic and
      arrhythmogenic cardiomyopathy), the valves (bicuspid aortic valve, mitral valve
      prolapse) and the conduction system (pre-excitation syndromes). These structural
      heart disorders may be detected by ECG and/or echo. The employment of these tools
      at pre-participation screening can help to identify concealed anomalies, which
      may play a major role in early diagnosis, risk stratification, and prevention of
      sudden death.

PMID- 22457201
TI  - Combination of calcitriol and dietary soy exhibits enhanced anticancer activity
      and increased hypercalcemic toxicity in a mouse xenograft model of prostate
      cancer.
AB  - BACKGROUND: The potential role of vitamin D and soy in prostate cancer (PCa)
      prevention/treatment has gained much attention in recent years. In this study, we
      evaluated the anticancer activity of calcitriol, the active form of vitamin D,
      dietary soy, and their combinations in a mouse model of PCa. METHODS: Athymic
      male nude mice bearing PC-3 human PCa xenografts received diets containing 10 or
      20 kcal% soy, calcitriol injections, or a combination of dietary soy and
      calcitriol. Changes in tumor growth, serum levels of 1,25(OH)(2)D and calcium,
      and regulation of tumor gene expression were examined. RESULTS: The combination
      treatments resulted in substantially greater inhibition of tumor growth than
      either agent alone. Soy diets alone caused a modest elevation in serum
      1,25(OH)(2)D, whereas the calcitriol-soy combinations led to substantially
      elevated serum 1,25(OH)(2) D, hypercalcemia, and in some cases lethal toxicity.
      The combinations enhanced calcitriol activity in regulating target gene
      expression, including greater up-regulation of anti-proliferative (p21, IGFBP-3)
      and pro-apoptotic (Bax) genes, increased inhibition of anti-apoptotic (Bcl-2) and
      cell cycle promoting (cyclin D1) genes, and suppression of prostaglandin (PG)
      synthesis and signaling (COX-2, 15-PGDH, PG receptors). Increases in serum
      calcium were accompanied by elevated expression of intestinal calcium absorption
      genes (TRPV6, calbindin-9k). CONCLUSIONS: Soy increases the bioavailability of
      endogenous and administered calcitriol, thereby enhancing its anticancer effects
      and risk of hypercalcemia. Since both agents are easily available as dietary
      supplements, the increased potential for hypercalcemic toxicity becomes an
      important factor when considering the combined use of vitamin D and soy in PCa
      therapy.

PMID- 22457202
TI  - Knockdown of angiopoietin-2 suppresses metastasis in human pancreatic carcinoma
      by reduced matrix metalloproteinase-2.
AB  - Angiopoietin-2 (Ang2) has been shown highly expressed in resected human
      pancreatic carcinoma samples, and has tightly combination with tumor
      angiogenesis, but the role in metastasis of it is less clear. We were, therefore,
      interested in exploring the effects of Ang2 silencing on the invasion and
      metastasis of pancreatic carcinoma. Lentivirus (LV)-mediated Ang2 small hairpin
      RNA (LV-RNAi) and mock lentivirus (LV-NC) were transfected into pancreatic
      carcinoma cell line MIA PaCa-2. Groups were designed in this study: the control
      group (MIA PaCa-2 cells), the LV-NC group (cells transfected with the LV-NC), the
      LV-RNAi-KD1 group (cells transfected with LV-RNAi of knock down sequence (1) and
      the LV-RNAi-KD2 group (cells transfected with LV-RNAi of knock down sequence (2).
      Boyden chamber transwell assay was used to detect the cell invasion change. The
      protein levels of Ang2, MMP-2, and MMP-9 gene and mRNA level of MMP-2, MMP-9 were
      detected by Western blot and real-time polymerase chain reaction, respectively.
      Orthotopic pancreatic carcinoma xenotransplantation model were successfully built
      with MIA PaCa-2 cells injection. After treatment with intraperitoneal injection
      of LV-RNAi-KD2 (LV-RNAi), mice growth, liver function test, tumor volume and
      peritoneal metastatic numbers were observed and counted. Moreover, expression of
      Ang2, MMP-2, MMP-9 were measured by immunohistochemistry. Ang2 expression were
      successfully knocked down in two LV-RNAi groups, especially in the LV-RNAi
      KD2group. Compared with the control group and the LV-NC group, the mRNA and
      protein level of MMP-2 gene were downregulated significantly in LV-RNAi groups,
      also the invasion cell number decreased in boyden chamber transwell assay after
      LV-RNAi transfection. Meanwhile, no obvious MMP-9 gene expression changes were
      found among all the groups. LV-RNAi injection inhibited pancreatic carcinoma
      metastasis and growth in vivo by downregulating the expression of MMP-2 not MMP
      9. Most importantly, LV-mediated gene therapy with Ang2 knockdown exhibited
      almost no toxicity in vivo. These findings demonstrate that Ang2 gene silencing
      exert an anti-metastasis effect in vitro and in vivo, and Ang2 targeted gene
      therapy has the potential to serve as a novel way for pancreatic carcinoma
      treatment.

PMID- 22457205
TI  - Mechanisms underlying decreased hepatic triacylglycerol and cholesterol by
      dietary bitter melon extract in the rat.
AB  - In these studies, we focused on finding the mechanism(s) underlying the bitter
      melon (Momordica charantia L.) methanol fraction (MF)-dependent reduction in the
      concentration of hepatic triacylglycerol (TAG) and cholesterol in the rat. Rats
      were fed diets containing low (5 %) fat for 2 weeks (experiment 1), or low (5 %)
      and high (15 %) fat for a longer period of 8 weeks (experiment 2). MF was
      supplemented at 1 % level in both experiments. After feeding, rats were
      sacrificed, and their livers were prepared as slices and hepatocytes, followed by
      incubation with [1(2)-14C] acetate or [1-14C] oleic acid (18:1 n-6). Under these
      conditions, we found that rats fed diets containing MF, as compared to those
      without MF, showed: (1) no adverse effects on food intake and growth, (2) a
      decreased hepatic TAG and total cholesterol, irrespective of the difference in
      dietary fat level or feeding period, and (3) a decreased incorporation of [1(2)
      (14C] acetate and [1-14C] oleic acid into TAG of liver slices and hepatocytes. MF
      supplemented rats also showed no altered incorporation of labeled acetate into
      cholesterol and cholesterol ester, an increased fecal excretion of neutral
      steroids, but not of acidic steroids, and an enhanced mRNA abundance of carnitine
      palmitoylacyltransferase I, which is the rate-limiting enzyme for fatty acid
      oxidation. These results suggest that dietary MF decreases hepatic TAG synthesis
      while enhancing fatty acid oxidation, thereby reducing the concentration of
      hepatic TAG. The liver cholesterol-lowering effect of MF, however, is probably
      mediated through an increased fecal excretion of neutral steroids, without an
      effect on cholesterogenesis.

PMID- 22457213
TI  - Results of surgical resection in pelvic Ewing's sarcoma.
AB  - OBJECTIVE: To evaluate the results of patients with non-metastatic Ewing's
      sarcoma of the pelvis treated with surgical resection as part of their
      multimodality treatment METHODS: Twenty-six patients treated between September
      2000 and September 2009 were evaluated. Thirteen resections included the
      acetabulum and 13 did not. Thirteen resections excluding the acetabulum had no
      reconstruction. Arthrodesis was done in two, extracorporeal radiation and
      reimplantation in two, and pseudarthrosis in nine patients. RESULTS: Three
      patients had involved margins. Seventeen patients had good response to
      chemotherapy and nine were poor responders. Twenty-one patients were available
      for follow-up. The follow-up ranged from 4 to 129 months (mean 36 months).
      Thirteen patients are currently alive. There was one local recurrence. On Kaplan
      Meier analysis the overall survival was 72% at 5 years. The 3-year survival in
      good responders to chemotherapy was 94% compared to 30% in poor responders. The
      Musculoskeletal Tumor Society Score ranged from 23 to 29, with patients in whom
      the acetabulum was retained having better function compared to patients in whom
      acetabulum was resected. CONCLUSION: Surgery provides good local control and
      oncologic outcomes with acceptable function in these patients.

PMID- 22457206
TI  - Pilot study of vascular health in survivors of Hodgkin lymphoma.
AB  - BACKGROUND: Vascular-related toxicities have been reported among survivors of
      Hodgkin lymphoma (HL), but their genesis is not well understood. PROCEDURE:
      Fasting blood samples from 25 previously irradiated HL survivors were analyzed
      for biomarkers that can reveal underlying inflammation and/or endothelial cell
      activation: high-sensitivity C-reactive protein (hsCRP), triglycerides, total
      cholesterol, high-density lipoprotein (HDL), apolipoprotein beta, lipoprotein
      (a), fibrinogen, circulating endothelial cells (CECs), and vascular cell adhesion
      molecule-1 (VCAM-1) expression. Values were compared to subjects in the Coronary
      Artery Risk Development in Young Adults (CARDIA) study. CECs and VCAM-1 were
      compared to healthy controls. RESULTS: Survivors (76% male), median age 17.6
      years (5-33) at diagnosis, 33.0 years (19-55) at follow-up, included stages IA (n
      = 6), IIA (n = 10), IIB (n = 2), IIIA (n = 4), and IVA (n = 3) patients. Twenty
      four received at least chest radiation therapy (RT) (median dose 3,150 cGy;
      range: 175-4,650 cGy), one received neck only; 14 (56%) had a history of
      anthracycline exposure (median dose: 124 mg/m(2) range: 63-200 mg/m2). Compared
      to CARDIA subjects, mean hsCRP (3.0 mg/L +/- 2.0 vs. 1.6 +/- 1.9), total
      cholesterol (194.1 mg/dl +/- 33.2 vs. 179.4 +/- 32.9), lipoprotein (a) (34.2
      mg/dl +/- 17.5 vs. 13.8 +/- 17.5), and fibrinogen (342.0 mg/dl +/- 49.1 vs. 252.6
      +/- 48.4) were significantly elevated. CECs (2.3 cells/ml +/- 1.5 vs. 0.34 +/-
      1.4) were significantly elevated compared to controls. No difference in VCAM-1
      expression (51.1% +/- 36.8 vs. 42.3 +/- 35.6) was detected. CONCLUSION: HL
      survivors exposed to RT have evidence of vascular inflammation, dyslipidemia, and
      injury suggestive of early atherogenesis.

PMID- 22457212
TI  - Hedgehog signaling inhibition by the small molecule smoothened inhibitor GDC-0449
      in the bone forming prostate cancer xenograft MDA PCa 118b.
AB  - BACKGROUND: Hedgehog signaling is a stromal-mesenchymal pathway central to the
      development and homeostasis of both the prostate and the bone. Aberrant Hedgehog
      signaling activation has been associated with prostate cancer aggressiveness. We
      hypothesize that Hedgehog pathway is a candidate therapeutic target in advanced
      prostate cancer. We confirm increased Hedgehog signaling in advanced and bone
      metastatic castrate resistant prostate cancer and examine the pharmacodynamic
      effect of Smoothened inhibition by the novel reagent GDC-0449 in an experimental
      prostate cancer model. METHODS: Hedgehog signaling component expression was
      assessed in tissue microarrays of high grade locally advanced and bone metastatic
      disease. Male SCID mice subcutaneously injected with the bone forming xenograft
      MDA PCa 118b were treated with GDC-0449. Hedgehog signaling in the tumor
      microenvironment was assessed by proteomic and species specific RNA expression
      and compared between GDC-0449 treated and untreated animals. RESULTS: We observe
      Hedgehog signaling in high grade locally advanced and bone marrow infiltrating
      disease. Evidence of paracrine activation of Hedgehog signaling in the tumor
      xenograft, was provided by increased Sonic Hedgehog expression in human tumor
      epithelial cells, coupled with increased Gli1 and Patched1 expression in the
      murine stromal compartment, while normal murine stroma did not exhibit Hh
      signaling expression. GDC-0449 treatment attenuated Hh signaling as evidenced by
      reduced expression of Gli1 and Ptch1. Reduction in proliferation (Ki67) was
      observed with no change in tumor volume. CONCLUSIONS: GDC-0449 treatment is
      pharmacodynamically effective as evidenced by paracrine Hedgehog signaling
      inhibition and results in tumor cell proliferation reduction. Understanding these
      observations will inform the clinical development of therapy based on Hedgehog
      signaling inhibition.

PMID- 22457214
TI  - Degeneration and recovery of the neuromuscular junction after application of
      extracorporeal shock wave therapy.
AB  - It is known that free nerve endings are degenerated after application of shock
      waves. We therefore hypothesized that the application of shock waves to muscle
      induces dysfunction of neuromuscular transmission at neuromuscular junctions. We
      investigated changes in neuromuscular transmission in response to shock wave
      application. Sprague-Dawley rats were used in this study. Two thousand shock
      waves at an energy flux density of 0.18 mJ/mm(2) were applied to their right calf
      muscles. Neuromuscular junctions of gastrocnemius muscles were evaluated using
      rhodamine-alpha-bungarotoxin on the day of treatment (n  =  5). Amplitude and
      latency of compound muscle action potentials were measured on the day of
      treatment and 1, 2, 4, 6, and 8 weeks after treatment (n  =  10, each group).
      Degenerated acetylcholine receptors existed in all treated muscles. Although the
      action potential amplitude on the treated side was significantly less than on the
      control side from the day of treatment (25.1 +/- 7.8 vs. 34.5 +/- 9.1, p  = 
      0.012) to 6 weeks (27.9 +/- 7.2 vs. 34.5 +/- 7.2, p  =  0.037), there was no
      significant difference at 8 weeks. There was no significant difference in
      transmission latency between the groups. The application of shock waves to muscle
      induced a transient dysfunction of nerve conduction at neuromuscular junctions.

PMID- 22457216
TI  - Targeting TNF receptors in rheumatoid arthritis.
AB  - Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that signals through
      two distinct receptors, TNFR1 and TNFR2. TNF is essentially involved in the
      pathogenesis of various inflammatory and autoimmune diseases. Blocking TNF, in
      turn, has been proven to be highly effective in treating a variety of diseases.
      However, the role of its two receptors in these conditions is not very well
      understood. It is established that TNFR1 is mainly responsible for the
      detrimental effects of TNF. However, accumulating evidence suggests differential
      or even opposing effects of TNFR2 in the pathogenesis of a number of inflammatory
      and autoimmune conditions. In this review, we summarize the available data
      concerning biological and functional properties of the two TNF receptors and
      potential therapeutic consequences of these insights.

PMID- 22457217
TI  - A cohort study of permanently reduced work ability in breast cancer patients.
AB  - PURPOSE: The aims of this cohort study were to explore various longitudinal
      aspects of employment and disability pension due to permanently reduced work
      ability among women with breast cancer and to investigate the impact of breast
      cancer on income. PATIENTS AND METHODS: In a national register-based controlled
      cohort study from Norway, 1,548 women diagnosed with breast cancer (all stages)
      between 1992 and 1996 at the age 45-54 years and 1,548 cancer-free women matched
      for age, municipality and civil status were followed for up to 14 years. Medical
      data from the Cancer Registry of Norway were linked with longitudinal data on
      employment, social security benefits and socio-demography collected from other
      national official registries. RESULTS: Compared to cancer-free controls, breast
      cancer patients were significantly more likely to receive disability pension
      (hazard ratio (HR) 2.7, 95% CI 2.3-3.2) after adjustment for unmatched socio
      demographic variables (education, income and children <18 years in the
      household). Adjusted HR in breast cancer stage I patients was 1.8 (95% CI 1.5
      2.3) and 3.0 (95% CI 2.4-3.8) in stage II/III patients compared to controls. The
      risk increased with mastectomy compared to breast-conserving surgery (HR 1.5, 95%
      CI 1.2-1.9). At the end of the observation period, employment rates were higher
      in non-disabled patients than in non-disabled controls (82% vs. 77%, p = 0.008).
      Working breast cancer patients experienced a temporary negative effect on
      employment income. CONCLUSION: A considerable proportion of women with breast
      cancer will over time experience permanently reduced work ability and become
      disability pension holders. In case of reduced work ability in breast cancer
      survivors, medical personel caring for them should consider and discuss with them
      rehabilitation and workplace adjustment in order to prevent early disability
      pension.

PMID- 22457218
TI  - Cancer perceptions: implications from the 2007 Health Information National Trends
      Survey.
AB  - INTRODUCTION: Research has demonstrated associations between sociodemographic
      characteristics and illness perceptions; however, the impact of cancer exposure
      through personal or family diagnoses is not well-studied. The purposes of this
      study were to examine different cancer beliefs and disparities in cancer beliefs
      across groups of individuals with distinct cancer histories and to identify
      whether cancer history predicts a set of cancer beliefs. METHODS: Using
      Leventhal's Common Sense Model and data from the 2007 Health Information National
      Trends Survey (N = 7,172), we constructed multivariable logistic regression
      models to evaluate the effect of different stimuli, including cancer experience
      on cancer perceptions (e.g., prevention, causation, outcome, worry). RESULTS:
      Findings indicated significant associations between cancer history and cancer
      perceptions. Individuals with family and personal cancer histories were more
      likely than individuals without any cancer history to worry about getting cancer
      (OR = 3.55, 95 %CI = 2.53-4.99), agree they will develop cancer in the future (OR
      = 8.81, 95 %CI = 6.12-12.67) and disagree that cancer is most often caused by a
      person's behavior or lifestyle (OR = 1.24, 95 %CI = 1.01-1.52). CONCLUSIONS:
      Cancer history affects perceptions throughout the cancer continuum. Additionally,
      cancer history may influence coping behaviors and outcomes. Cancer education and
      survivorship programs should assess important variables such as cancer history to
      more effectively tailor services and monitor evolving needs throughout cancer
      care. IMPLICATIONS FOR CANCER SURVIVORS: Integrating cancer history information
      into patient education programs tailored to an individual's needs may better
      empower survivors and their family members to effectively promote informed
      decision-making about screening and preventive health behaviors, manage cancer
      worry, and enhance quality of life.

PMID- 22457220
TI  - Hyperimmunoglobulinemia in pediatric Gaucher patients in Southern Brazil.

PMID- 22457221
TI  - Immigrant workers and worker's compensation: the need for reform.
AB  - Foreign-born workers in the United States suffer high rates of workplace injuries
      and accidents. Both for workers who are unauthorized to work in the United States
      and for those who are present legally under guest worker programs, access to
      workers' compensation benefits presents nearly insurmountable barriers. Some of
      these are longstanding, such as employer retaliation and aggressive litigation of
      claims. Some are more recent and related to the increasingly transnational
      character of the workforce and to barriers put in place by administrators. This
      is a legal overview of the cases, statutes, and policies that act as barriers to
      access for immigrant workers, conducted by reviewing case law and basic
      compensation statutes in all fifty states. Where these are known, policies that
      keep workers locked out of workers' compensation are also discussed. It concludes
      that reform of the system is needed in order to ensure its standing as an
      insurance program with universal application. As part of that reform, further
      state by state research and advocacy would discover specific administrative
      practices in each state that keep immigrant workers from receiving the benefits
      to which they are entitled.

PMID- 22457219
TI  - Unmet adolescent and young adult cancer survivors information and service needs:
      a population-based cancer registry study.
AB  - PURPOSE: We described unmet information and service needs of adolescent and young
      adult (AYA) cancer survivors (15-39 years of age) and identified sociodemographic
      and health-related factors associated with these unmet needs. METHODS: We studied
      523 AYAs recruited from seven population-based cancer registries, diagnosed with
      acute lymphocytic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, germ cell
      cancer, or sarcoma in 2007-2008. Participants completed surveys a median of 11
      months from diagnosis. Multivariable logistic regression analyses were used to
      estimate associations between unmet (information and service) needs and
      sociodemographic and health-related factors. RESULTS: More than half of AYAs had
      unmet information needs relating to their cancer returning and cancer treatments.
      AYAs needing services, but not receiving them, ranged from 29 % for in-home
      nursing to 75 % for a support group. The majority of AYAs who needed a pain
      management expert, physical/occupational therapist, mental health worker, or
      financial advice on paying for health care did not receive services. In
      multivariable analyses, older participants, men, participants of non-white
      race/ethnicity, and participants who reported less than excellent general health
      or fair/poor quality of care were more likely to report unmet information needs.
      Factors associated with both unmet service and information needs included
      physical health or emotional problems interfering with social activities or
      having >=3 physical treatment-related symptoms. CONCLUSIONS: Recently diagnosed
      AYA cancer survivors have substantial unmet information needs varying by
      demographic and health-related factors. IMPLICATIONS FOR CANCER SURVIVORS: We
      identified subgroups of AYA cancer survivors with high unmet needs that can be
      targeted for interventions and referrals.

PMID- 22457222
TI  - Spontaneous rupture of a middle colic artery aneurysm arising from superior
      mesenteric artery dissection: Diagnosis by color Doppler ultrasonography and CT
      angiography.
AB  - Both middle colic artery (MCA) aneurysm and spontaneous dissection of the
      superior mesenteric artery (SMA) are rare. We report the first case of
      concomitancy of both conditions, diagnosed by ultrasonography and CT angiography.
      A 56-year-old man with abrupt abdominal pain and hypovolemic shock was diagnosed
      initially with ruptured MCA aneurysm by color Doppler ultrasonography. Computed
      tomography and angiography confirmed MCA aneurysm and showed that it was arising
      from the false lumen of an SMA dissection and was probably associated with
      segmental arterial mediolysis. The MCA aneurysm was treated successfully by
      transcatheter coil embolization, and the SMA dissection was treated
      conservatively.

PMID- 22457223
TI  - Heat shock proteins induction reduces stress kinases activation, potentially
      improving insulin signalling in monocytes from obese subjects.
AB  - Induction of heat shock proteins (Hsp) 72 and 27 can improve insulin signalling
      in obesity and type 2 diabetes via inhibition of key stress kinases. In metabolic
      disease, altered insulin signalling, as illustrated by increased serine
      phosphorylation of insulin receptor substrate (IRS)-1 (Ser312), is not confined
      to muscle or liver and can also affect other tissues and cell types, potentially
      impairing their primary biological function. This study specifically investigated
      insulin-stimulated glucose metabolism in monocytes and examined the impact of HSP
      induction on insulin signalling. Control (CG, BMI < 25 kg/m(2)) or obese (OG, BMI
      > 30 kg/m(2)) participants were included in the study. Glucose transporter
      (GLUT)4 expression on monocytes, phosphorylated JNK, IKK-beta and IRS-1, as well
      as Hsp27 and Hsp72, were measured in monocytes under fasting conditions. GLUT4
      expression was also measured during an oral glucose tolerance test (OGTT). HSP
      induction as well as JNK, IKK-beta activation and IRS-1 serine phosphorylation
      was investigated following heat stress. Obese patients showed lower GLUT4 levels
      on monocytes during the OGTT. pJNK, pIKK-beta and pIRS-1 levels were increased in
      OG with pJNK and pIKK-beta levels positively correlated with serine pIRS-1 and
      negatively with GLUT4 supporting their role in insulin resistance. Heat exposure
      induced Hsp72 and Hps27, but only in CG for the latter, and decreased pJNK, pIKK
      beta and pIRS-1. Our results show that induction of Hsp72 and 27 via heat stress
      is associated with inactivation of stress kinases and reduced serine pIRS-1 in
      monocytes from obese participants. This indicates that metabolic diseases can
      also affect monocyte metabolism via cellular stress that can be modulated via HSP
      induction.

PMID- 22457224
TI  - Time-resolved spin-labeled balanced steady-state free precession cineangiography
      for visualizing intracardiac shunt: technical considerations and clinical
      feasibility.
AB  - A time-resolved spin-labeled cineangiographic MRI technique for visualizing blood
      flow in the heart and defects of the atrial septum is described. The method
      utilizes a spin labeling preparation and a time-resolved balanced steady-state
      free precession imaging readout that enhances blood in the left atrium or right
      atrium and suppresses background signal through inversion recovery. Four
      volunteer studies and 10 patient studies were performed at 1.5 T to characterize
      the signal properties and to test the clinical feasibility of depicting atrial
      septal defects. In volunteers, the spin-labeled cineangiographic method depicted
      intracardiac blood flow patterns and demarcated the intact atrial septum. Peak
      target to adjacent atrial chamber contrast-to-noise ratios of 84 and 94 were
      obtained 758 and 689 ms postlabeling; 50% of peak contrast-to-noise ratio was
      maintained for 803 and 599 ms in the left atrium and right atrium, respectively.
      In all patients with an atrial septal defect, the spin-labeled cineangiographic
      method demonstrated left-to-right flow and maintained good morphological
      assessment of surrounding cardiac structures. Right-to-left flow was seen in
      three patients. In conclusion, the spin-labeled cineangiographic method displayed
      favorable signal properties in volunteers and demonstrated shunting in patients
      with atrial septal defects. The technique is expected to be a viable alternative
      to the few techniques available for visualizing blood flow in the heart.

PMID- 22457225
TI  - Is allergy related to Meniere's disease?
AB  - Meniere's disease (MD) is characterized by episodic rotational vertigo,
      fluctuating sensorineural hearing loss, aural pressure, and tinnitus. The cause
      of MD is thought to be multifactorial, with anatomic and genetic contributions.
      Allergy is thought to be one of the possible extrinsic factors that, when
      combined with underlying intrinsic factors, may lead to MD. We review the
      epidemiologic associations of MD and allergy and review the recent literature on
      the association of allergy and MD.

PMID- 22457226
TI  - [Atypical Parkinson syndromes--recent advances in diagnosis and therapy].
AB  - The term "atypical Parkinson syndromes" usually encompasses the following
      diseases: multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and
      corticobasal syndrome (CBS). The differential diagnosis is still a challenge even
      for a movement disorders specialist, not least because of the distinct
      therapeutic approaches and disease prognosis. The aim of this review is to
      provide an overview of current diagnostic criteria and therapeutic approaches and
      to cite recent findings from clinical and experimental studies.

PMID- 22457227
TI  - Methylation of the RASSF1A promoter is predictive of poor outcome among patients
      with Wilms tumor.
AB  - BACKGROUND: Wilms tumor (WT) has a survival rate of 90% following multimodality
      therapy. Nevertheless, there are some groups of patients with event-free survival
      rates less than 75%. In addition to clinical prognostic factors, loss of
      heterozygosity at 1p and/or 16q has been used to determine treatment intensity.
      However, the incidence of this abnormality is low, and new biomarkers are still
      needed. PROCEDURE: We analyzed methylation status of three tumor suppressor
      genes; Ras-association domain family 1 protein, isoform A (RASSF1A), DCR2, and
      CASP8, in 84 WTs using conventional methylation-specific PCR (cMSP), and the
      results were correlated with outcome. Furthermore, we analyzed the methylation
      status of RASSF1A by quantitative MSP (qMSP) in 171 WTs, and evaluated clinical
      and genetic differences between the methylated and unmethylated tumors. RESULTS:
      RASSF1A was the most frequently methylated gene identified by cMSP, and
      associated with a poor outcome. Patients with a RASSF1A-methylated tumor had
      shorter overall and event-free survival periods (P = 0.043 and 0.018,
      respectively), when a cut-off value of 7% by qMSP was used. The methylation was
      more frequent in tumors of older children than younger children (P < 0.001), and
      in advanced-stage tumors than early stage tumors (P = 0.001). However,
      multivariate analysis could not confirm the prognostic significance of RASSF1A
      methylation, possibly because of a small number of advanced stage tumors
      examined. RASSF1A methylation was correlated with LOH at 1p and/or 16q (P =
      0.017), but not with WT1 abnormality, suggesting the methylation and LOH to
      involve the same tumorigenic pathway. CONCLUSIONS: The methylation status of
      RASSF1A might be a novel biomarker to predict outcome of WT patients.

PMID- 22457228
TI  - Intratendinous gouty tophus mimics patellar tendonitis in an athlete.
AB  - We describe the imaging and pathologic features of a case of intratendinous
      patellar gouty tophus incidentally discovered in a patient with knee pain. The
      possibility of intratendinous gouty tophus must be kept in mind by sports
      physicians, especially in the management of patellar tendinopathy in athletes. It
      may be associated with other injuries, such as enthesopathies or partial tendon
      tears.

PMID- 22457229
TI  - Laryngeal cancer and silica dust exposure: a systematic review and meta-analysis.
AB  - BACKGROUND: Individual epidemiological studies generally lack the power to
      examine the association between silica exposure or silicosis and laryngeal
      cancer. We summarized pertinent evidence from published literature by using meta
      analysis. METHODS: A systematic literature search was performed to identify
      cohort and case-control studies, and the method of meta-analysis was used to
      combine standardized mortality ratios (SMRs) or standardized incidence ratios
      (SIRs) from cohort studies and odds ratios (ORs) from case-control studies.
      RESULTS: A significantly increased risk of laryngeal cancer (pooled OR = 1.39,
      95% confidence interval (95% CI): 1.17-1.67) among workers exposed to silica dust
      was observed by combining six case-control studies with adjustment for smoking
      and alcohol consumption. A similarly increased but statistically non-significant
      risk estimate was observed from cohort studies, with a pooled SMR of 1.38 (95%
      CI: 0.79-1.96) for silicosis cases; and a pooled SMR of 1.13 (95% CI: 0.82-1.45)
      and a pooled SIR of 1.50 (95% CI: 0.59-2.42) for workers with silica dust
      exposure. CONCLUSION: This systematic review demonstrated a weak association
      between silica or silicosis and laryngeal cancer. Owing to the inherent
      limitations of the original studies, interpretation of the results of this meta
      analysis should be cautious.

PMID- 22457231
TI  - Modulation of fungicidal potential of Anabaena strains by light and temperature.
AB  - The regulation of fungicidal and hydrolytic enzyme activity was investigated in a
      set of cyanobacterial strains belonging to the genus Anabaena (Anabaena laxa
      RPAN8, Anabaena iyengarii RPAN9, Anabaena variabilis RPAN59 and Anabaena
      oscillarioides RPAN69), with A. variabilis RPAN16 serving as negative control.
      Time course studies undertaken with cultures incubated under different light and
      temperature conditions revealed enhancement in growth and fungicidal activity
      under continuous light (CL) and light dark (LD, 16:8) conditions and temperature
      of 30  degrees C and 40  degrees C. A significant increase of 3-18 % in
      chitosanase activity was recorded in all the 4-week-old cultures under CL
      condition and at 40  degrees C. Endoglucanase activity of RPAN8 and 9 was
      twofolds higher than the other strains under all light/dark conditions and
      temperature in the 4-week-old cultures, while continuous dark (CD) enhanced
      CMCase activity in RPAN69. This study provided useful information regarding the
      most suitable conditions of light and temperature for maximizing hydrolytic
      enzyme activity and fungicidal activity, as a prelude to their effective use as
      biocontrol agents.

PMID- 22457230
TI  - Receptor for advanced glycation end products (RAGE) and implications for the
      pathophysiology of heart failure.
AB  - The receptor for advanced glycation end products (RAGE) is expressed in the heart
      in cardiomyocytes, vascular cells, fibroblasts, and in infiltrating inflammatory
      cells. Experiments in murine, rat, and swine models of injury suggest that RAGE
      and the ligands of RAGE are upregulated in key injuries to the heart, including
      ischemia/reperfusion injury, diabetes, and inflammation. Pharmacological
      antagonism of RAGE or genetic deletion of the receptor in mice is strikingly
      protective in models of these stresses. Data emerging from human studies suggest
      that measurement of levels of RAGE ligands or soluble RAGEs in plasma or serum
      may correlate with the degree of heart failure. Taken together, the ligand-RAGE
      axis is implicated in heart failure and we predict that therapeutic antagonism of
      RAGE might be a unique target for therapeutic intervention in this disorder.

PMID- 22457232
TI  - Isolation, identification, and characterization of Vibrio cholerae from the
      Danube River in Slovakia.
AB  - The occurrence of Vibrio cholerae, an important aquatic pathogen, was assessed in
      the surface water of the Danube River near Bratislava. The isolates were
      distinguished by biochemical tests and grouped by ARDRA to three clusters
      corresponding to three species (V. cholerae, Vibrio metschnikovii, and Aeromonas
      spp.). The identification of V. cholerae was confirmed by multiplex PCR using
      primer pairs targeted to ompW gene (membrane protein), ctxA gene (toxicity gene),
      and toxR gene (regulatory gene). None from the isolated V. cholerae from surface
      water contained ctxA gene; seven of them possessed toxR gene. Serotyping of V.
      cholerae isolates with polyvalent O antiserum and O/139 antiserum was negative.
      All isolates of V. cholerae were susceptible to chloramphenicol, rifampicin,
      tetracycline, variable to ampicillin, and resistant to kanamycin and
      streptomycin.

PMID- 22457233
TI  - Feasibility of shutter-speed DCE-MRI for improved prostate cancer detection.
AB  - The feasibility of shutter-speed model dynamic-contrast-enhanced MRI
      pharmacokinetic analyses for prostate cancer detection was investigated in a
      prebiopsy patient cohort. Differences of results from the fast-exchange-regime
      allowed (FXR-a) shutter-speed model version and the fast-exchange-limit
      constrained (FXL-c) standard model are demonstrated. Although the spatial
      information is more limited, postdynamic-contrast-enhanced MRI biopsy specimens
      were also examined. The MRI results were correlated with the biopsy pathology
      findings. Of all the model parameters, region-of-interest-averaged K(trans)
      difference [DeltaK(trans) = K(trans)(FXR-a) - K(trans)(FXL-c)] or two-dimensional
      K(trans)(FXR-a) vs. k(ep)(FXR-a) values were found to provide the most useful
      biomarkers for malignant/benign prostate tissue discrimination (at 100%
      sensitivity for a population of 13, the specificity is 88%) and disease burden
      determination. (The best specificity for the fast-exchange-limit-constrained
      analysis is 63%, with the two-dimensional plot.) K(trans) and k(ep) are each
      measures of passive transcapillary contrast reagent transfer rate constants.
      Parameter value increases with shutter-speed model (relative to standard model)
      analysis are larger in malignant foci than in normal-appearing glandular tissue.
      Pathology analyses verify the shutter-speed model (FXR-a) promise for prostate
      cancer detection. Parametric mapping may further improve pharmacokinetic
      biomarker performance.

PMID- 22457234
TI  - Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult
      cases with post-Chornobyl papillary thyroid carcinoma.
AB  - BACKGROUND: Increased incidence of papillary thyroid carcinoma (PTC) is observed
      as a consequence of radiation exposure in connection to the Chornobyl nuclear
      plant accident in 1986. In this study, we report a cohort of adult Ukrainian
      patients diagnosed with PTC from 2004 to 2008 following exposure at the age of 18
      years or younger. METHODS: In total, 70 patients were identified and clinically
      characterized. The common BRAF 1799T>A mutation was assessed by pyrosequencing,
      the RET/PTC1 and RET/PTC3 (NCOA4) rearrangements by RT-PCR, and the expression of
      Ki-67 (MIB-1 index), BCL2, cyclin A, and cyclin D1 by immunohistochemistry.
      RESULTS: In total, 46/70 (66%) cases carried a BRAF mutation and/or a RET/PTC
      rearrangement. A BRAF mutation was detected in 26 tumors, RET/PTC1 in 20 cases,
      and RET/PTC3 in four cases. In four of these cases, BRAF mutation and RET/PTC
      rearrangement were coexisting. The BRAF mutation was underrepresented among PTCs
      with accompanying chronic lymphocytic thyroiditis (CLT) compared with PTCs
      without this feature (12 vs 44%). MIB-1 proliferation index determined by double
      staining with leukocyte common antigen was low (mean 0.8%; range 0.05-4.5%).
      Moreover, increased expression of cyclin A was observed in PTCs with a tumor size
      >2 cm compared with PTCs <=2 cm (1.2 vs 0.6%). BCL2 and cyclin D1 showed frequent
      expression but without associations to clinical characteristics or amplification
      of the CCND1 locus. CONCLUSIONS: Our results suggest that this cohort has
      frequent BRAF mutation, RET/PTC1 rearrangement, and low proliferation index.
      Furthermore, BRAF 1799T>A was underrepresented in PTCs with CLT, and cyclin A
      expression was associated with increased PTC tumor size.

PMID- 22457235
TI  - Tumour recurrence and enlargement in patients with craniopharyngioma with and
      without GH replacement therapy during more than 10 years of follow-up.
AB  - OBJECTIVE: Most patients who have been treated for craniopharyngioma (CP) are GH
      deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and
      one of the concerns with long-term GHRT is the risk of tumour progression.
      Therefore, the objective was to study tumour progression in CP patients on long
      term GHRT. DESIGN: Case-control study. PATIENTS AND METHODS: The criteria for
      inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular
      imaging. This resulted in 56 patients (mean age at diagnosis 25+/-16 years) with
      a mean duration of GHRT of 13.6+/-5.0 years. As controls, 70 CP patients who had
      not received GHRT were sampled with regard to follow-up, gender, age at diagnosis
      and initial radiation therapy (RT). RESULTS: The 10-year tumour progression-free
      survival rate (PFSR) for the entire population was 72%. There was an association
      (hazard ratio, P value) between PFSR and initial RT (0.13, 0.001) and residual
      tumour (3.2, 0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the
      control group. Substitution with GHRT resulted in the following associations to
      PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01)
      and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for
      the GHRT group and 65% for the control group. CONCLUSIONS: In patients with CP,
      the most important prognostic factors for the PFSR were initial RT and residual
      tumour after initial treatment. Long-term GHRT did not affect the PFSR in
      patients with CP.

PMID- 22457236
TI  - Overall and cause-specific mortality in GH-deficient adults on GH replacement.
AB  - OBJECTIVE: Hypopituitarism is associated with an increased mortality rate but the
      reasons underlying this have not been fully elucidated. The purpose of this study
      was to evaluate mortality and associated factors within a large GH-replaced
      population of hypopituitary patients. DESIGN: In KIMS (Pfizer International
      Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of
      follow-up were available. METHODS: This study analysed standardised mortality
      ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of
      adequacy of GH replacement. Statistical significance was set to P<0.05. RESULTS:
      All-cause mortality was 13% higher compared with normal population rates (SMR,
      1.13; 95% confidence interval, 1.04-1.24). Significant associations were female
      gender, younger age at follow-up, underlying diagnosis of Cushing's disease,
      craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After
      controlling for confounding factors, there were statistically significant
      negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement
      and SMR. For cause-specific mortality there was a negative association between 1
      year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and
      malignancies (P=0.044). CONCLUSIONS: GH-replaced patients with hypopituitarism
      demonstrated a modest increase in mortality rate; this appears lower than that
      previously published in GH-deficient patients. Factors associated with increased
      mortality included female gender, younger attained age, aetiology and lower IGF1
      SDS during therapy. These data indicate that GH replacement in hypopituitary
      adults with GH deficiency may be considered a safe treatment.

PMID- 22457237
TI  - GH secretagogue receptor gene polymorphisms are associated with stature
      throughout childhood.
AB  - CONTEXT: Ghrelin plays a major role in GH physiology and energy metabolism.
      Polymorphisms of its receptor (GH secretagogue receptor (GHSR)) may influence
      childhood growth and weight regulation. OBJECTIVE: To correlate GHSR
      polymorphisms with auxological parameters throughout childhood in a healthy
      cohort. STUDY DESIGN: Longitudinal retrospective population-based genetic
      association study. SUBJECTS AND METHODS: GHSR genotypes were evaluated in 1362
      children and compared with height/length, weight, and body mass index (BMI) data
      across an observation span of 10 years (0, 1, 3, 5, 8, and 10 years). Five
      different GHSR SNPs (rs2922126, rs2981464, rs482204, rs562416, and rs572169),
      minor allele frequency >0.1, were genotyped. Identification of potential genetic
      associations with height, weight, and BMI, using additive and dominant/recessive
      models, was optimized by comparing allele or genotype frequencies between the
      tallest and the shortest 27% of subjects for each auxological variable.
      Significance of association was evaluated by chi(2) test. RESULTS: The rs482204
      TT genotype, vs TC/CC, was associated with greater stature across the entire
      observation period (P<0.05). Similarly, the rs562416 TT genotype, vs TG/GG,
      correlated positively with tall stature at 3, 8, and 10 years. Other SNPs and
      genotypes showed no association with height at any age. No association was found
      between any tested SNPs and weight or BMI. CONCLUSIONS: Longitudinal
      investigation between birth and 10 years in a population-based cohort revealed a
      significant association of the rs482204 and rs562416 GHSR polymorphisms on
      height, whereas no association between GHSR polymorphisms and weight or BMI was
      ascertainable.

PMID- 22457238
TI  - Chondroitin sulfate and epidermal growth factor immobilization after plasma
      polymerization: a versatile anti-apoptotic coating to promote healing around
      stent grafts.
AB  - Bioactive coatings constitute an interesting approach to enhance healing around
      implants, such as stent-grafts used in endovascular aneurysm repair. Three
      different plasma techniques, namely NH3 plasma functionalization and atmospheric-
      or low-pressure plasma polymerization, are compared to create amino groups and
      covalently bind CS and EGF bioactive molecules on PET. The latter presents the
      greatest potential. CS + EGF coating is shown to strongly decrease cell apoptosis
      and cell depletion in serum-free medium, while increasing cell growth compared to
      unmodified PET. This versatile biomimetic coating holds promise in promoting
      vascular repair around stent-grafts, where resistance to apoptosis is a key
      issue.

PMID- 22457239
TI  - Comparison of transcranial color Doppler sonography without and with contrast
      enhancement for detection and characterization of intracranial aneurysms.
AB  - OBJECTIVE: To compare the diagnostic value of transcranial color Doppler
      sonography (TCCS) with contrast-enhanced transcranial color Doppler sonography
      (CE-TCCS) for the detection and characterization of intracranial aneurysms.
      METHODS: Thirty patients highly suspected of having an intracranial aneurysm were
      imaged using TCCS and CE-TCCS. The ability to detect the aneurysms and determine
      their size and location accurately was compared with findings from digital
      subtraction angiography. RESULTS: The overall sensitivity of CE-TCCS was greater
      than that of TCCS (24/30 versus 20/30, respectively) (p = 0.125), but the
      difference was not significant. Neither TCCS nor CE-TCCS could detect the three
      small (<=5 mm diameter) aneurysms. The detection rate for larger aneurysms (5-15
      mm diameter, n = 17) was nonsignificantly greater with CE-TCCS (14/17) than with
      TCCS (11/17) (p = 0.438). Similarly, CE-TCCS detected more large or giant
      aneurysms (>16 mm diameter) than TCCS (10/10 versus 9/10, respectively) but the
      difference was not significant (p = 1.000). The benefit of contrast enhancement
      was identical for aneurysms >=10 mm or <10 mm in diameter. All (7/7) middle
      cerebral artery aneurysms were detected by both TCCS and CE-TCCS. CE-TCCS yielded
      similar or slightly better results than TCCS for all other aneurysm locations.
      CONCLUSION: CE-TCCS can improve the sensitivity and detection rate of
      intracranial aneurysms >=5 mm in size.

PMID- 22457240
TI  - Associations between rationing of nursing care and inpatient mortality in Swiss
      hospitals.
AB  - OBJECTIVE: To explore the relationship between inpatient mortality and implicit
      rationing of nursing care, the quality of nurse work environments and the patient
      to-nurse staffing ratio in Swiss acute care hospitals. DESIGN: Cross-sectional
      correlational design. SETTING: Eight Swiss acute care hospitals examined in a
      survey-based study and 71 comparison institutions. PARTICIPANTS: A total of 165
      862 discharge abstracts from patients treated in the 8 RICH Nursing Study (the
      Rationing of Nursing Care in Switzerland Study) hospitals and 760 608 discharge
      abstracts from patients treated in 71 Swiss acute care hospitals offering similar
      services and maintaining comparable patient volumes to the RICH Nursing
      hospitals. MAIN OUTCOME MEASURES: The dependent variable was inpatient mortality.
      Logistic regression models were used to estimate the effects of the independent
      hospital-level measures. RESULTS: Patients treated in the hospital with the
      highest rationing level were 51% more likely to die than those in peer
      institutions (adjusted OR: 1.51, 95% CI: 1.34-1.70). Patients treated in the
      study hospitals with higher nurse work environment quality ratings had a
      significantly lower likelihood of death (adjusted OR: 0.80, 95% CI: 0.67-0.97)
      and those treated in the hospital with the highest measured patient-to-nurse
      ratio (10:1) had a 37% higher risk of death (adjusted OR: 1.37, 95% CI: 1.24
      1.52) than those in comparison institutions. CONCLUSIONS: Measures of rationing
      may reflect care conditions that place hospital patients at risk of negative
      outcomes and thus deserve attention in future hospital outcomes research studies.

PMID- 22457241
TI  - Finding the right indicators for assessing quality midwifery care.
AB  - OBJECTIVE: To identify a set of indicators for monitoring the quality of
      maternity care for low-risk women provided by primary care midwives and general
      practitioners (GPs) in the Netherlands. DESIGN: A Project Group (midwives, GPs,
      policymakers and researchers) defined a long list of potential indicators based
      on the literature, national guidelines and expert opinion. This list was assessed
      against the AIRE (Appraisal of Indicators through Research and Evaluation)
      instrument criteria, resulting in a short list of draft indicators. In a two
      round Delphi survey, a multidisciplinary group of stakeholders reviewed the
      elaborated draft indicators, rating both the relationship between indicator and
      quality of care and the feasibility. SETTING AND PARTICIPANTS: A
      multidisciplinary expert panel consisting of 28 midwives, 2 GPs, 3 obstetricians
      and 3 maternity assistants, randomly selected from different regions in the
      Netherlands. INTERVENTION: None. MAIN OUTCOME MEASURE: Set of quality indicators
      for midwifery care. RESULTS: The Project Group generated a list of 115 potential
      indicators which was reduced to 35 using the AIRE criteria. The 35 draft
      indicators were discussed by a Delphi panel. In total, 26 indicators were
      recommended by the participants as relevant indicators of midwifery care,
      representing several levels of measurement. Eight structure indicators, 12
      process indicators and 6 outcome indicators were addressing the various phases of
      midwifery care. CONCLUSIONS: We identified a set of quality indicators concerning
      midwifery care provision in a low-risk population. Practicing maternity care
      providers adopted the large majority (83%) of the draft indicators proposed as a
      feasible set of indicators, describing the structure, process and outcome. The
      input from multidisciplinary experts in the process of identifying the right
      indicators showed to be essential in all phases of development.

PMID- 22457242
TI  - Carotid baroreceptor activation for the treatment of resistant hypertension and
      heart failure.
AB  - Carotid baroreceptors play an important role in blood pressure regulation through
      modification of sympathetic nervous activity. Conditions associated with
      increased sympathetic activity, such as resistant hypertension and heart failure,
      represent potential targets for carotid baroreceptor activation. Recent
      technological advances made available a small device, like a pacemaker, that
      constantly activates carotid baroreceptors. Primary experimental and clinical
      data obtained from use of this device point toward significant blood pressure
      reduction in patients with resistant hypertension, as well as beneficial effects
      on cardiac structure and function. A large feasibility trial revealed promising
      results; however, the first randomized study in patients with resistant
      hypertension raised several concerns regarding the efficacy and safety of
      baroreceptor activation with the device. This review critically evaluates
      available data obtained with carotid baroreceptor activation, emphasizing data
      acquired during the past year, and discusses the advantages and disadvantages as
      well as the future prospects of this intervention.

PMID- 22457244
TI  - Renal denervation in human hypertension: mechanisms, current findings, and future
      prospects.
AB  - Denervating the human kidney to improve blood pressure control is an old
      therapeutic concept first applied on a larger scale by surgeons in the 1920s.
      With the advent of modern pharmacology and the development of powerful drugs to
      lower blood pressure, approaches to directly target the sympathetic nerves were
      more or less abandoned. Over the past 2-3 years, however, we have witnessed
      enormous renewed interest in novel and minimally invasive device-based approaches
      to specifically target the renal nerves. The enthusiasm is fueled by promising
      results from proof-of-concept studies and clinical trials demonstrating
      convincing blood pressure-lowering effects in the majority of treated patients,
      and perhaps even more so by observations indicating potential additional benefits
      relating to common comorbidities of hypertension, such as impaired glucose
      metabolism, renal impairment, left ventricular hypertrophy, and others. Herein we
      review the current findings and assess whether these high hopes are justified.

PMID- 22457247
TI  - [Everything new in May].

PMID- 22457245
TI  - Suppressed hepcidin expression correlates with hypotransferrinemia in copper
      deficient rat pups but not dams.
AB  - Copper deficiency leads to anemia but the mechanism is unknown. Copper deficiency
      also leads to hypoferremia, which may limit erythropoiesis. The hypoferremia may
      be due to limited function of multicopper oxidases (MCO) hephaestin in
      enterocytes or GPI-ceruloplasmin in macrophages of liver and spleen whose
      function as a ferroxidase is thought essential for iron transfer out of cells.
      Iron release may also be limited by ferroportin (Fpn), the iron efflux
      transporter. Fpn may be lower following copper deficiency because of impaired
      ferroxidase activity of MCO. Fpn is also dependent on the liver hormone hepcidin
      as Fpn is degraded when hepcidin binds to Fpn. Anemia and hypoferremia both down
      regulate hepcidin by separate mechanisms. Current studies confirmed and extended
      earlier studies with copper-deficient (CuD) rats that suggested low hepicidin
      resulted in augmented Fpn. However, current studies in CuD dams failed to confirm
      a correlation that hepcidin expression was associated with low transferrin
      receptor 2 (TfR2) levels and also challenged the dogma that holotransferrin can
      explain the correlation with hepcidin. CuD dams exhibited hypoferremia, low liver
      TfR2, anemia in some rats, yet no depression in Hamp expression, the hepcidin
      gene. Normal levels of GDF-15, the putative erythroid cytokine that suppresses
      hepcidin, were detected in plasma of CuD and iron-deficient (FeD) dams.
      Importantly, FeD dams did display greatly lower Hamp expression. Normal hepcidin
      in these CuD dams is puzzling since these rats may need extra iron to meet needs
      of lactation and the impaired iron transfer noted previously.

PMID- 22457243
TI  - Vitamin D and cardiovascular risk.
AB  - Vitamin D deficiency is a common condition that has well-documented effects on
      musculoskeletal health. A growing body of literature has related vitamin D
      deficiency to other chronic disorders, including cardiovascular disease. Several
      plausible biological mechanisms have been postulated to explain this association,
      including the effect of poor vitamin D status on intermediate risk factors (eg,
      hypertension and diabetes), neurohormonal activation, inflammation, and cardiac
      remodeling. These mechanisms have been explored in experimental and animal
      studies, as well as several small interventional studies. The results of the
      controlled trials have not been conclusive to date. In this review, we summarize
      the existing studies investigating the effects of vitamin D on cardiovascular
      health, and propose that additional well-designed, prospective, randomized
      controlled trials are necessary to delineate the appropriate role of vitamin D
      supplementation in reducing the burden of cardiovascular disease.

PMID- 22457249
TI  - Minimal clinically important differences in the Carpal Tunnel Questionnaire after
      carpal tunnel release.
AB  - Minimal clinically important difference is the smallest difference in the score
      of an outcome instrument that patients perceive as important. A prospective
      observational study was conducted involving 66 consecutive patients undergoing
      limited open carpal tunnel release. Patients completed the Carpal Tunnel
      Questionnaire (CTQ) before surgery and 3 months post-surgery. A transition item
      for patient satisfaction after 3 months of surgery was used as an anchor.
      Receiver operator characteristic curves were used to determine the minimal
      clinically important differences for the CTQ and its two subscales that best
      separated satisfied and unsatisfied patients. A 0.92 point change in the CTQ, a
      1.14 point change in the symptom subscale, and a 0.74 point change in the
      function subscale indicated a clinically relevant threshold of satisfaction, and
      those values were greater than what could be accounted for by measurement errors.

PMID- 22457248
TI  - Reducing artifacts in one-dimensional Fourier velocity encoding for fast and
      pulsatile flow.
AB  - When evaluating the severity of valvular stenosis, the peak velocity of the blood
      flow is routinely used to estimate the transvalvular pressure gradient. One
      dimensional Fourier velocity encoding effectively detects the peak velocity with
      an ungated time series of spatially resolved velocity spectra in real time.
      However, measurement accuracy can be degraded by the pulsatile and turbulent
      nature of stenotic flow and the existence of spatially varying off-resonance. In
      this work, we investigate the feasibility of improving the peak velocity
      detection capability of one-dimensional Fourier velocity encoding for stenotic
      flow using a novel echo-shifted interleaved readout combined with a variable
      density circular k-space trajectory. The shorter echo and readout times of the
      echo-shifted interleaved acquisitions are designed to reduce sensitivity to off
      resonance. Preliminary results from limited phantom and in vivo results also
      indicate that some artifacts from pulsatile flow appear to be suppressed when
      using this trajectory compared to conventional single-shot readouts, suggesting
      that peak velocity detection may be improved. The efficiency of the new
      trajectory improves the temporal and spatial resolutions. To realize the proposed
      readout, a novel multipoint-traversing algorithm is introduced for flexible and
      automated gradient-waveform design.

PMID- 22457250
TI  - A new type of carpal coalition.

PMID- 22457251
TI  - Hand infection due to Mycobacterium neoaurum.

PMID- 22457252
TI  - Modelling for crossed Kirschner wire fixation.

PMID- 22457253
TI  - Bilateral sequential closed traumatic wrist flexor tendon ruptures.

PMID- 22457254
TI  - The deleterious effects of exsanguination with a tight bandage on tourniquet
      tolerance in the upper arm.
AB  - Tourniquet tolerance is affected by the method of exsanguination. Two commonly
      used methods, tight elastic bandaging and limb elevation, were tested to
      determine their effects on upper extremity tourniquet tolerance in 23 healthy
      adult volunteers. We found that tourniquet tolerance was significantly lower
      among the bandaging group compared with the limb elevation group (average 19.4
      min and 24.1 min, respectively). Overall, the tourniquet tolerance was not
      affected by hand dominance or arm circumference.

PMID- 22457255
TI  - Index finger clawing associated with fracture of the distal radius.

PMID- 22457256
TI  - Long-term follow-up of periarterial sympathectomy for chronic digital ischaemia.
AB  - This study investigates long-term clinical results (> 10 years) of periarterial
      sympathectomy in chronic ischaemic digits compared with intermediate-term results
      (3 years). Periarterial sympathectomy via the palm and volar wrist was carried
      out on 11 hands of seven patients with digital ischaemia but no gangrene or
      severe ulceration. The aetiology of ischaemia was Buerger's disease in four
      hands, collagen disease in three hands, and repetitive digital trauma in four
      hands. Subjective symptoms were evaluated at a mean follow-up period of 12 years.
      The efficacy of surgery was assessed objectively using thermography and
      plethysmography. Although five of seven patients continued on oral vasodilators
      and antiplatelet agents until the final follow-up, improvement of symptoms was
      maintained in all patients between intermediate- and long-term evaluations. Our
      results suggest that periarterial sympathectomy via the palm and wrist could
      prevent long-term aggravation of symptoms of chronic digital ischaemia when
      combined with adequate postoperative drug therapy.

PMID- 22457257
TI  - Load transfer through the radiocarpal joint and the effects of partial wrist
      arthrodesis on carpal bone behaviour: a finite element study.
AB  - A finite element model of the wrist was developed to simulate mechanical changes
      that occur after surgery of the wrist. After partial arthrodesis, the wrist will
      experience altered force transmission during loading. Three different types of
      partial arthrodesis were investigated - radiolunate, radioscaphoid, and
      radioscapholunate - and compared with the healthy untreated wrist. The results
      showed that the compressive forces on the radiocarpal joint decreased compared
      with the untreated wrist with both radiolunate and radioscaphoid fusions. The
      load transmission through the midcarpal joints varied depending on arthrodesis
      type. The forces in the extrinsic ligaments decreased with the fusion, most
      noticeably in the dorsal radiotriquetral ligament, but increased in the dorsal
      scaphotriquetral ligament. From the results of the study it can be concluded that
      the radioscapholunate fusion shows the most biomechanically similar behaviour out
      of the three fusion types compared with the healthy wrist. The modelling
      described in this paper may be a useful approach to pre-operative planning in
      wrist surgery.

PMID- 22457258
TI  - Posterior interosseous neurectomy for extensive idiopathic avascular necrosis of
      the capitate in an adolescent.

PMID- 22457259
TI  - A novel approach to manage skin toxicity caused by therapeutic agents targeting
      epidermal growth factor receptor.

PMID- 22457260
TI  - Mitogenic activity of sulfated chitosan and cellulose derivatives is related to
      protection of FGF-2 from proteolytic cleavage.
AB  - Novel chitosan (CHS) and cellulose sulfates (CSs) are studied regarding their
      mitogenic activity and their protective effect against proteolytic digestion of
      FGF-2. An intermediate degree of sulfation (DS(S) ) and lower concentration of
      CHS have superior effect on 3T3 cell growth while the mitogenic activity of CS
      increases with DS(S)  and concentration. Experiments with trypsin as model
      proteinase show that protection of FGF-2 from proteolytic digestion depends on
      DS(S)  and the concentration of derivatives in the same manner as cell growth.
      Studies on stability of FGF-2 added to cultures of 3T3 cells show that the FGF-2
      concentration remains higher in the presence of derivatives. Results indicate
      that the mitogenic activity of CHS and CS is due to protection of FGF-2 from
      proteolytic cleavage.

PMID- 22457261
TI  - Coexistence of multiple and widespread cardiovascular complications in a patient
      with Marfan syndrome.
AB  - Inherited connective tissue diseases such as Marfan syndrome are frequently
      associated with cardiovascular manifestations. Aortic involvement with dilation
      and dissection is the most common finding and the major cause of death in Marfan
      syndrome patients. We report the echocardiographic study of a 53-year-old male
      patient with uncommon coexistence of cardiovascular abnormalities typical of
      connective tissue disease at first clinical presentation in acute clinical
      setting: dissection of the descending aorta associated with severe mitral
      regurgitation due to leaflet flail and massive aortic insufficiency due to
      ascending aortic enlargement, leading to left ventricular dilation and
      dysfunction.

PMID- 22457262
TI  - Automatic off-resonance correction in spiral imaging with piecewise linear
      autofocus.
AB  - Off-resonance generates blurring artifacts in spiral images. Applications that
      often utilize spiral trajectories, such as fine-resolution imaging and rapid
      scanning, typically preclude the measurement of accurate field maps needed for
      effective off-resonance correction. Automatic deblurring, or autofocus,
      algorithms have been developed to estimate the field map directly from the
      corrupted data prior to off-resonance correction, eliminating the need for field
      map measurements. These algorithms rely in whole or in part on optimizing an
      objective function, and suffer from problems related to the accurate minimization
      and utility of the function. Here, a new method is presented to correct off
      resonance blurring automatically without an objective function using a piecewise
      linear framework. Local linear field maps are estimated with a combination of k
      space spectral analysis and mapdrift, an image feature-based correlation
      technique, for subsequent piecewise linear deblurring. This approach enables
      field map estimation without optimization, provides accurate off-resonance
      correction, is suitable for low signal-to-noise ratio and fine-resolution
      applications, and does not require access to the raw data. Deblurred images from
      fine-resolution spiral scans of a phantom and healthy volunteers at 3T show that
      the proposed method can be superior to conventional autofocus and comparable to
      field map-based correction.

PMID- 22457264
TI  - "We're going through a lot of struggles that people don't even know about": the
      need to understand African American males' help-seeking for mental health on
      multiple levels.
AB  - Young adult Black males face challenges related to addressing their mental health
      needs, yet there is much more to know about their help-seeking experiences.
      Twenty-seven Black males, recruited from four community-based organizations,
      participated in four focus groups to explore perceptions of help-seeking for
      mental health. Identified themes, which function at individual, social network,
      community, and health care system levels, may facilitate or hinder Black males'
      mental health help-seeking. Themes included (a) "taking care of it oneself" as
      opposed to seeking help from someone; (b) issues engaging sources of help,
      including the ability to trust providers or the relationship closeness with
      social network members; and (c) "tipping points" that activate help-seeking to
      avert crises. Study findings provide initial evidence about the importance of
      addressing mental health interventions for Black males on multiple levels beyond
      the individual including engaging men's social supports, community, and the
      health care system.

PMID- 22457265
TI  - Iatrogenic fistula between coronary artery bypass graft and cardiac venous
      system.

PMID- 22457266
TI  - Transient constrictive pericarditis in systemic lupus erythematous.

PMID- 22457267
TI  - Pulmonary vein spontaneous echocontrast and stroke after pulmonary lobectomy.
AB  - Assessment of possible cardiac sources of cerebral embolism is a frequent
      indication for transesophageal echocardiography. We report the case of a patient
      with a previous left upper pulmonary lobe resection who presented with an
      ischemic stroke suggestive of cardioembolic origin. A dense spontaneous echo
      contrast was found in the left upper pulmonary vein stump, which, in the absence
      of other potential causes of stroke, was considered to be related to the embolic
      event. We discuss the clinical significance of this finding as a possibly
      underappreciated source of systemic embolization.

PMID- 22457268
TI  - Modified Look-Locker T1 evaluation using Bloch simulations: human and phantom
      validation.
AB  - Modified Look-Locker imaging is frequently used for T(1) mapping of the
      myocardium. However, the specific effect of various MRI parameters (e.g.,
      encoding scheme, modifications of flip angle, heart rate, T(2), and inversion
      times) on the accuracy of T(1) measurement has not been studied through Bloch
      simulations. In this work, modified Look-Locker imaging was characterized through
      a numerical solution for Bloch equations. MRI sequence parameters that may affect
      T(1) accuracy were systematically varied in the simulation. For validation,
      phantoms were constructed with various T(2) and T(1) times and compared with
      Bloch equation simulations. Human volunteers were also evaluated with various
      pulse sequences parameters to assess the validity of the numerical simulations.
      There was close agreement between simulated T(1) times and T(1) times measured in
      phantoms and volunteers. Lower T(2) times (i.e., <30 ms) resulted in errors
      greater than 5% for T(1) determination. Increasing maximum inversion time value
      improved T(1) accuracy particularly for precontrast myocardial T(1). Balanced
      steady-state free precession k space centric encoding improved accuracy for short
      T(1) times (post gadolinium), but linear encoding provided improved accuracy for
      precontrast T(1) values. Lower flip angles are preferred if the signal-to-noise
      ratio is sufficiently high. Bloch simulations for modified Look-Locker imaging
      provide an accurate method to comprehensively quantify the effect of pulse
      sequence parameters on T(1) accuracy. As an alternative to otherwise lengthy
      phantom studies or human studies, such simulations may be useful to optimize the
      modified Look-Locker imaging sequence and compare differences in T(1)-derived
      measurements from different scanners or institutions.

PMID- 22457269
TI  - Behavioral counseling for cardiovascular disease prevention in primary care
      settings: a systematic review of practice and associated factors.
AB  - Cardiovascular disease carries a substantial public health burden. Physician
      advice on modifying behavioral risk factors is effective, yet the practice of and
      factors associated with behavioral counseling in primary care have not been
      systematically investigated. The authors conducted a systematic review that
      identified 18 studies providing data on 6,338 physicians. The provision of
      preventive services differed by patients' individual risk. Physicians' counseling
      on smoking cessation was most commonly reported. The proportions of physicians
      counseling about nutrition and physical activity were notably lower and few
      physicians took further action by using more intensive counseling approaches. As
      studies were mainly based on self-reports, current delivery of preventive
      services may be overestimated. There is a need to increase the frequency of
      behavioral counseling in primary care settings, particularly for nutrition and
      physical activity, and to emphasize that counseling may also benefit individuals
      without cardiovascular disease risk factors.

PMID- 22457270
TI  - LKB1 mutations and their correlation with LKB1 and Rheb expression in bladder
      cancer.
AB  - Although there are extensive studies on the genetics of bladder cancer, several
      questions remain unanswered. One of the pathways which are altered in bladder
      cancer is the mTOR signaling pathway. In the present study, we analyzed the
      expression of Rheb gene and genetic alterations in the LKB1 gene which are the
      key components of mTOR pathway. Nine exons of the LKB1 gene were analyzed by
      direct sequencing in 51 bladder cancer patients. To investigate the expression of
      Rheb and LKB1, real-time quantitative RT-PCR was performed in bladder tumor and
      normal bladder tissue samples. We did not observed a statistically significant
      difference in Rheb or LKB1 expression between the tumor and normal tissue
      samples. We detected a novel missense mutation creating stop codon in a high
      percent of the tumor samples. Five different single nucleotide substitutions were
      also observed in the introns. Our results indicate that LKB1 gene may play a role
      in the progression of bladder cancer.

PMID- 22457272
TI  - The changing spectrum of microbial keratitis: is microsporia increasing as a
      cause of microbial keratitis or is it a previously unrecognised cause?

PMID- 22457273
TI  - Severe immune dysregulation affects CD4+CD25(hi)FoxP3+ regulatory T cells in HIV
      infected patients with low-level CD4 T-cell repopulation despite suppressive
      highly active antiretroviral therapy.
AB  - We hypothesized that CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Tregs) could be
      involved in the high immune activation existing in patients with low-level CD4 T
      cell repopulation under suppressive high active antiretroviral therapy
      (hereafter, "LLR patients"). Sixteen LLR patients, 18 human immunodeficiency
      virus (HIV)-infected controls (hereafter, "HIV controls"), and 16 healthy
      subjects were included. The frequency of CD4(+)CD25(hi)FoxP3(+) and HIV-specific
      Treg suppressive function were assessed. Relationships between Treg and CD4/CD8
      activation (HLA-DR/CD38) and the frequency of naive CD4 T-cells were assessed.
      Low-level patients showed a higher Treg frequency but reduced HIV-specific
      immunosuppressive functions than HIV controls. Whereas in healthy subjects a
      strong negative correlation between Tregs and activated CD8 T cells emerged (r = 
      0.75, P < .001), it appeared disrupted in both HIV-infected groups (r = -0.06 and
      P = .83 for LLR patients; r = -0.11 and P = .68 for and HIV controls).
      Nevertheless, in LLR patients, Tregs negatively correlated with naive CD4 T cells
      (r = -0.60, P = .01), whereas there was no such correlation in HIV controls (r = 
      0.19, P = .46) or healthy subjects (r = -0.10, P = .73). Remarkably, a higher
      ratio of Tregs to naive CD4 T cells was observed in LLR patients than in HIV
      controls (P = .001) and healthy subjects (P < .001). We conclude that LLR
      patients have important alterations in immunoregulation involving
      CD4(+)CD25(hi)FoxP3(+) Tregs. In this scenario, the role of Tregs seems to be
      more related to the control of the naive CD4 T-cell homeostatic proliferation,
      rather than to the immune activation.

PMID- 22457275
TI  - Staphylococcus aureus activation of caspase 1/calpain signaling mediates invasion
      through human keratinocytes.
AB  - The USA300 strains of Staphylococcus aureus are the major cause of skin and soft
      tissue infection in the United States. Invasive USA300 infection has been
      attributed to several virulence factors, including protein A and the alpha
      hemolysin (Hla), which cause pathology by activating host signaling cascades.
      Here we show that S. aureus exploits the proinflammatory bias of human
      keratinocytes to activate pyroptosis, a caspase 1-dependent form of inflammatory
      cell death, which was required for staphylococci to penetrate across a
      keratinocyte barrier. Keratinocyte necrosis was mediated by calpains, Ca(2+)
      dependent intracellular proteases whose endogenous inhibitor, calpastatin, is
      targeted by Hla-induced caspase 1. Neither Panton-Valentine leukocidin nor
      protein A expression was essential, but inhibition of either calpain or caspase 1
      activity was sufficient to prevent staphylococcal invasion across the
      keratinocytes. These studies suggest that pharmacological interruption of
      specific keratinocyte signaling cascades as well as targeting the Hla might
      prevent invasive skin infection by staphylococci.

PMID- 22457274
TI  - HIV infection and the incidence of malaria among HIV-exposed children from
      Tanzania.
AB  - OBJECTIVE: To determine whether human immunodeficiency virus (HIV) infection is
      associated with increased risk of malaria incidence and recurrence in children.
      METHODS: Newborn infants of HIV-infected mothers were enrolled at 6 weeks and
      followed for 2 years. HIV status was assessed by enzyme-linked immunosorbant
      assay and confirmed by HIV DNA polymerase chain reaction. Malaria was defined as
      (1) physician-diagnosed clinical malaria; (2) probable malaria, in which
      laboratory testing is requested for parasitemia; and (3) blood smear-confirmed
      malaria. Cox proportional hazards models estimated hazard ratios (HRs) for
      development of first and second malaria episodes, and generalized estimating
      equation models estimated malaria rate differences per 100-child-years in
      relation to time-updated HIV status. RESULTS: Child HIV infection was associated
      with clinical (HR, 1.34; 95% confidence interval [CI], 1.12-1.61), probable (HR,
      1.47; 95% CI, 1.19-1.81), and confirmed (HR, 1.67; 95% CI, 1.18-2.36) malaria
      episodes. Per 100 child-years, HIV-infected children experienced 88 (95% CI, 65
      113), 36 (95% CI, 19-53), and 20 (95% CI, 9-31) more episodes of clinical,
      probable, and confirmed malaria episodes, respectively, than HIV-uninfected
      children. Among children with >=1 malaria episodes, those with HIV infection
      developed second clinical (HR, 1.28; 95% CI, 1.04-1.57), probable (HR, 1.60; 95%
      CI, 1.26-2.14), and confirmed (HR, 2.27; 95% CI, 1.06-3.89) malaria sooner than
      HIV-uninfected children. CONCLUSIONS: HIV infection is a risk factor for the
      development of malaria. Proactive malaria disease prevention and treatment is
      warranted for all children, particularly those with HIV infection in settings of
      coendemicity.

PMID- 22457276
TI  - How Staphylococcus aureus breaches our skin to cause infection.

PMID- 22457277
TI  - A functional single-nucleotide polymorphism in the promoter of the gene encoding
      interleukin 6 is associated with susceptibility to tuberculosis.
AB  - BACKGROUND: Genetic variation influences susceptibility or resistance to
      tuberculosis. Interleukin 6 (IL-6) contributes to protection against tuberculosis
      in mice. However, its role in regulating susceptibility or resistance to
      tuberculosis in humans is unclear. METHODS: Genotyping of polymorphisms in IL-6
      and IL-6R (CD126) genes was performed in 2 independent cohorts, an experimental
      population (495 cases and 358 controls) and a validation population (1383 cases
      and 1149 controls). The associations of the variants with tuberculosis were
      tested using 2 case-control association studies. In addition, the regulatory
      effects of single-nucleotide polymorphism rs1800796 (-572C > G) on IL-6
      production in plasma and CD14(+) monocyte cultures stimulated with a
      Mycobacterium tuberculosis (M. tuberculosis) product were assessed. RESULTS: The
      rs1800796 polymorphism is associated with increased resistance to tuberculosis
      (odds ratio [OR], 0.771; 95% confidential interval, .684-.870). The rs1800796GG
      genotype is strongly associated with reduced risk to tuberculosis (OR, 0.621; 95%
      CI, .460-.838). Interestingly, CD14(+) monocytes isolated from individuals with
      rs1800796GG genotype produced significantly less IL-6 in response to M.
      tuberculosis 19-kDa lipoprotein than those with CC or CG genotype. CONCLUSIONS:
      We identified a genetic polymorphism in the IL-6 promoter that regulates cytokine
      production and host resistance to pulmonary tuberculosis in Chinese populations.

PMID- 22457278
TI  - Association of polymorphisms of the mu opioid receptor gene with the severity of
      HIV infection and response to HIV treatment.
AB  - BACKGROUND: Mu opioid receptor (OPRM1) ligands may alter expression of chemokines
      and chemokine receptors involved in penetration of human immunodeficiency virus
      (HIV) type 1 into the cell. We suggest that OPRM1 variants may affect the
      pathophysiology of HIV infection. METHODS: DNA samples from 1031 eligible African
      Americans, Hispanics, and whites from the Women's Interagency HIV Study (WIHS)
      who were alive as of April 2006 were analyzed. We performed regression analysis
      of association of 18 OPRM1 variants with a change of viral load and CD4 cell
      count during 2 periods: between admission to WIHS and the start of highly active
      antiretroviral therapy (HAART) (interval X) and between the start of HAART and
      the most recent WIHS visit (interval Y), and examined the association of these
      variants with HIV status. RESULTS: Regardless of genotype, a significant decrease
      in viral load during interval X was found for each ethnicity. Whites with allele
      G of the functional polymorphism 118A > G (reference sequence rs1799971) showed a
      smaller decrease in viral load; those bearing minor alleles IVS1 + 1050A, IVS1 +
      14123A, and IVS2 + 31A showed a larger decrease in viral load over interval X
      (0.01 < P < .05). Hispanics with the same alleles showed a greater increase in
      CD4 cell count over interval Y (0.01 < P < .05). We found an association between
      OPRM1 variants and HIV status in African Americans and whites. CONCLUSIONS: OPRM1
      polymorphisms may alter the severity of HIV infection before and after HAART.

PMID- 22457280
TI  - Early and long-lasting alteration of effector CD45RA(-)Foxp3(high) regulatory T
      cell homeostasis during HIV infection.
AB  - Regulatory T-cell (Treg) quantification in human immunodeficiency virus (HIV)
      infection remains ill defined because of the lack of reliable specific markers to
      identify human Tregs and the diversity of clinical stages of HIV infection. Using
      a recently described Treg identification strategy based on CD45RA and Foxp3
      expression, we performed an extensive quantification of total, naive
      (CD45RA(+)Foxp3(low)), and effector (CD45RA(-)Foxp3(high)) Tregs in different
      contexts of HIV infection: primary HIV infection, long-term viremic patients,
      aviremic patients treated with highly active antiretroviral therapy, and HIV
      controllers. We showed that although total Treg percentages were mildly affected
      by HIV infection, Treg absolute numbers were significantly reduced in all groups
      studied. We demonstrated that although naive Treg numbers were essentially
      preserved, effector Tregs were consistently affected during HIV infection.
      Finally, we demonstrated that effector but not total or naive Treg numbers were
      negatively correlated with the magnitude of HIV-specific CD8 T-cell responses.

PMID- 22457281
TI  - A new class of synthetic peptide inhibitors blocks attachment and entry of human
      pathogenic viruses.
AB  - Many enveloped viruses, including herpes viruses, hepatitis B virus (HBV), and
      hepatitis C virus (HCV), and human immunodeficiency virus (HIV), are among the
      most important human pathogens and are often responsible for coinfections
      involving >=2 types of viruses. However, therapies that are effective against
      multiple virus classes are rare. Here we present a new class of synthetic anti
      lipopolysaccharide peptides (SALPs) that bind to heparan sulfate moieties on the
      cell surface and inhibit infection with a variety of enveloped viruses. We
      demonstrate that SALPs inhibit entry of human immunodeficiency virus type 1 (HIV
      1), herpes simplex virus (HSV) 1 and 2, HBV, and HCV to their respective host
      cells. Despite their high antiviral efficiency, SALPs were well tolerated, and
      neither toxicity nor measurable inhibitor-induced adverse effects were observed.
      Since these broad-spectrum antiviral peptides target a host cell rather than a
      viral component, they may also be useful for suppression of viruses that are
      resistant to antiviral drugs.

PMID- 22457282
TI  - Latent acyclovir-resistant herpes simplex virus type 1 in trigeminal ganglia of
      immunocompetent individuals.
AB  - Specific mutations within the hypervariable herpes simplex virus (HSV) gene
      thymidine kinase (TK) gene lead to acyclovir (ACV) resistance. To uncover the
      existence of latent ACV-resistant (ACV(R)) HSV-1, we determined the genetic and
      functional variability of the HSV-1 TK gene pool in paired trigeminal ganglia
      (TG) of 5 immunocompetent individuals. The latent virus pool consisted of a donor
      specific HSV-1 quasispecies, including one major ACV-sensitive (ACV(S)) and
      multiple phylogenetic-related minor ACV(S) and ACV(R) TK variants. Contrary to
      minor variants, major TK variants were shared between paired TG. The data
      demonstrate the coexistence of phylogenetic-related ACV(S) and ACV(R) latent HSV
      1 in human TG.

PMID- 22457283
TI  - Regulatory T cells in HIV-1 infection: the good, the bad, and the ugly.

PMID- 22457284
TI  - Phenotypic and functional characterization of human gammadelta T-cell subsets in
      response to influenza A viruses.
AB  - Like alphabeta T cells, human gammadelta T cells also have different subsets with
      distinct characteristics. Whether human Vgamma9Vdelta2 T cells have functionally
      different subsets in response to influenza A (fluA) viruses remains unknown. In
      this study, we show for the first time that both central (CD45RA(-)CD27(+)) and
      effector (CD45RA(-)CD27(-)) memory Vgamma9Vdelta2 T cells have similar levels of
      immediate interferon (IFN) gamma and cytotoxic responses to human and avian fluA
      virus-infected cells. In contrast, CD56(+) Vgamma9Vdelta2 T cells have
      significantly higher cytotoxicity against fluA virus-infected cells compared with
      their CD56(-) counterparts, whereas both subsets have similar IFN-gamma
      responses. We further demonstrate that the CD16-dependent degranulation pathway,
      but not antibody-dependent cell-mediated cytotoxicity, contribute to the superior
      cytotoxicity of CD56(+) Vgamma9Vdelta2 T cells. Our study provides further
      evidence for the phenotypic and functional characterization of human
      Vgamma9Vdelta2 T-cell subsets during fluA virus infection and may help improve
      the gammadelta T-cell-based immunotherapy for viral infection.

PMID- 22457285
TI  - Indirect protection and indirect measures of protection from rotavirus in adults.

PMID- 22457288
TI  - Common and diverse features of cocirculating type 2 and 3 recombinant vaccine
      derived polioviruses isolated from patients with poliomyelitis and healthy
      children.
AB  - BACKGROUND: Five cases of poliomyelitis due to type 2 or 3 recombinant vaccine
      derived polioviruses (VDPVs) were reported in the Toliara province of Madagascar
      in 2005. METHODS: We sequenced the genome of the VDPVs isolated from the patients
      and from 12 healthy children and characterized phenotypic aspects, including
      pathogenicity, in mice transgenic for the poliovirus receptor. RESULTS: We
      identified 6 highly complex mosaic recombinant lineages composed of sequences
      derived from different vaccine polioviruses and other species C human
      enteroviruses (HEV-Cs). Most had some recombinant genome features in common and
      contained nucleotide sequences closely related to certain cocirculating coxsackie
      A virus isolates. However, they differed in terms of their recombinant
      characteristics or nucleotide substitutions and phenotypic features. All VDPVs
      were neurovirulent in mice. CONCLUSIONS: This study confirms the genetic
      relationship between type 2 and 3 VDPVs, indicating that both types can be
      involved in a single outbreak of disease. Our results highlight the various ways
      in which a vaccine-derived poliovirus may become pathogenic in complex viral
      ecosystems, through frequent recombination events and mutations. Intertypic
      recombination between cocirculating HEV-Cs (including polioviruses) appears to be
      a common mechanism of genetic plasticity underlying transverse genetic
      variability.

PMID- 22457286
TI  - Opportunities and challenges for cost-efficient implementation of new point-of
      care diagnostics for HIV and tuberculosis.
AB  - Stakeholders agree that supporting high-quality diagnostics is essential if we
      are to continue to make strides in the fight against human immunodeficiency virus
      (HIV) and tuberculosis. Despite the need to strengthen existing laboratory
      infrastructure, which includes expanding and developing new laboratories, there
      are clear diagnostic needs where conventional laboratory support is insufficient.
      Regarding HIV, rapid point-of-care (POC) testing for initial HIV diagnosis has
      been successful, but several needs remain. For tuberculosis, several new
      diagnostic tests have recently been endorsed by the World Health Organization,
      but a POC test remains elusive. Human immunodeficiency virus and tuberculosis are
      coendemic in many high prevalence locations, making parallel diagnosis of these
      conditions an important consideration. Despite its clear advantages, POC testing
      has important limitations, and laboratory-based testing will continue to be an
      important component of future diagnostic networks. Ideally, a strategic
      deployment plan should be used to define where and how POC technologies can be
      most efficiently and cost effectively integrated into diagnostic algorithms and
      existing test networks prior to widespread scale-up. In this fashion, the global
      community can best harness the tremendous capacity of novel diagnostics in
      fighting these 2 scourges.

PMID- 22457289
TI  - Cross-species immunity following immunization with a circumsporozoite protein
      based vaccine for malaria.
AB  - Malaria continues to be a major public health concern, and there are concerted
      efforts to eliminate it. The quest for a vaccine remains a top priority, and
      vaccines based on the circumsporozoite protein (CSP) are among the lead
      candidates, with the RTS,S vaccine currently undergoing phase 3 testing in
      Africa. Previous studies have reported anti-CSP antibody-mediated enhancement of
      in vitro invasion of homologous sporozoites. This effect has been shown to be
      concentration dependent; high-level antibodies are inhibitory, whereas low-level
      antibodies lead to enhancement of invasion. Nondominant shared epitopes may lead
      to the generation of low titers of cross-reactive antibodies that may prove to be
      detrimental. We report cross-species recognition of Plasmodium falciparum and
      Plasmodium berghei sporozoites by anti-Plasmodium vivax CSP serum samples. In
      addition, we report that vaccination of mice with VMP001, a P. vivax CSP vaccine
      candidate, reduces, not enhances, P. berghei infection in mice.

PMID- 22457290
TI  - Interferon alpha-stimulated natural killer cells from patients with acute
      hepatitis C virus (HCV) infection recognize HCV-infected and uninfected hepatoma
      cells via DNAX accessory molecule-1.
AB  - BACKGROUND: Natural killer (NK) cells are an important component of the innate
      immune defense against viruses, including hepatitis C virus (HCV). The cell
      culture system using HCV-permissive Huh-7.5 cells make studies on interaction of
      NK cells and HCV-infected target cells possible. We used this system to
      characterize interactions of HCV-infected Huh-7.5 cells and NK cells from healthy
      controls and patients with acute HCV infection. METHODS: IFNalpha- and IL-2
      stimulated NK cells were cultured with HCV-infected hepatoma cells and
      subsequently analyzed (for degranulation and cytokine production) via multicolour
      flow cytometry. Luciferase assyas have been used to study inhibition of HCV
      replication. Further, PBMC from patients with acute hepatitis C as well as HCV
      infected Huh7.5 cells have been analyzed via flow cytometry for expression of NK
      cell receptors and ligands, respectively. RESULTS: After interferon (IFN) alpha
      stimulation, NK cells from healthy controls and patients with acute hepatitis C
      efficiently recognized both HCV-infected and uninfected hepatoma cells.
      Subsequent dissection of receptor-ligand interaction revealed a dominant role for
      DNAM-1 and a complementary contribution of NKG2D for NK cell activation in this
      setting. Furthermore, IFN-alpha-stimulated NK cells effectively inhibited HCV
      replication in a DNAM-1-dependent manner. CONCLUSIONS: Human NK cells recognize
      HCV-infected hepatoma cells after IFN-alpha stimulation in a DNAM-1-dependent
      manner. Furthermore, interaction of IFN-alpha-stimulated NK cells with HCV
      infected hepatoma cells efficiently reduced HCV replication. This study opens up
      future studies of NK cell interaction with HCV-infected hepatocytes to gain
      further insight into the pathogenesis of human HCV infection and the therapeutic
      effects of IFN-alpha.

PMID- 22457292
TI  - The more you look, the more you find: effects of hepatitis C virus testing
      interval on reinfection incidence and clearance and implications for future
      vaccine study design.
AB  - INTRODUCTION: Studies have explored whether spontaneous clearance of hepatitis C
      virus (HCV) infection decreases the likelihood of reinfection or increases the
      probability of clearance. This analysis investigates whether the conflicting
      findings from these studies could be due to differences in frequency of HCV RNA
      testing. METHODS: A model simulated the dynamics of HCV reinfection and clearance
      among a cohort of injection drug users. For different reinfection incidence and
      clearance rates, the model evaluated the accuracy of epidemiological studies that
      used different HCV testing frequencies. RESULTS: Experimental estimates for the
      reinfection incidence and clearance probability will be accurate (<20% error) if
      the testing interval is less than the reinfection clearance duration. Otherwise,
      experimental estimates can greatly underestimate the real values (<=66% error if
      reinfection duration is 1 month and the testing interval is 3 months).
      Uncertainty in experimental estimates also increases at lower reinfection
      incidences, whereas for lower clearance probabilities the uncertainty in the
      estimated clearance probability increases but estimated reinfection incidence
      decreases. DISCUSSION: Differences in HCV testing interval could account for most
      between-study variability in the estimated probability of clearing reinfections
      and is likely to have biased reinfection incidence estimates. Our findings
      suggest that a high reinfection clearance probability (>75%) is consistent with
      data.

PMID- 22457291
TI  - Staphylococcus epidermidis colonization is highly clonal across US cardiac
      centers.
AB  - BACKGROUND: Little is known about the clonality of Staphylococcus epidermidis in
      the United States, although it is the predominant pathogen in infections
      involving prosthetic materials, including ventricular assist devices (VADs).
      METHODS: Seventy-five VAD recipients at 4 geographically diverse US cardiac
      centers were prospectively followed up to 1 year of VAD support. The anterior
      nares, sternum, and (future) driveline exit site were cultured for S. epidermidis
      before VAD insertion and at 7 times after surgery. Infection isolates were also
      collected. Isolates were typed by pulsed-field gel electrophoresis. A subset
      underwent susceptibility testing and staphylococcal chromosomal cassette mec and
      multilocus sequence typing. RESULTS: A total of 1559 cultures yielded 565 S.
      epidermidis isolates; 254 of 548 typed isolates (46%) belonged to 1 of 7 clonal
      types as defined by pulsed-field gel electrophoresis. These clones were
      identified in up to 27 people distributed across all 4 cardiac centers. They
      caused 3 of 6 VAD-related infections. Disseminated clones were more antibiotic
      resistant than were less prevalent isolates (eg, 79% vs 54% methicillin
      resistant; P = .0021). CONCLUSIONS: This study revealed that healthcare
      associated S. epidermidis infection is remarkably clonal. We describe S.
      epidermidis clones that are highly resistant to antibiotics distributed across US
      cardiac centers. These clones may have determinants that enhance
      transmissibility, persistence, or invasiveness. Clinical Trials Registration.
      NCT01471795.

PMID- 22457293
TI  - Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects
      on antigen-specific B cells.
AB  - BACKGROUND: A 23-valent unconjugated pneumococcal polysaccharide vaccine (23vP),
      routinely administered at the age of 65, has limited effectiveness, and
      revaccination induces attenuated antibody responses. It is not known whether
      pneumococcal polysaccharide-protein conjugated vaccines (PCV), although highly
      effective in infants, offer any immunological advantages over 23vP in adults.
      METHODS: We immunized adults with schedules combining both PCV and 23vP and
      investigated B-cell responses to establish whether PCV7 (a 7-valent PCV) induced
      T-dependent responses in adults, to assess the role of memory B cells in 23vP
      induced antibody hyporesponsiveness, and to identify the B-cell subtypes
      involved. RESULTS: A single dose of PCV7 induced significant increases in
      serotype-specific memory B-cell populations in peripheral blood indicating a T
      dependent response. Conversely, immunization with 23vP resulted in a decrease in
      memory B-cell frequency. Furthermore, memory B-cell responses to subsequent
      immunization with PCV7, when given after 23vP, were attenuated. Notably, B1b
      cells, a subset important in protecting mice against pneumococci, were also
      depleted following immunization with 23vP in humans. CONCLUSIONS: This study
      indicates that PCV7 may have an immunological advantage over 23vP in adults and
      that 23vP-induced depletion of memory and B1b-cell subsets may provide a basis
      for antibody hyporesponsiveness and the limited effectiveness of 23vP. Clinical
      Trials Registration. ISRCTN: 78768849.

PMID- 22457294
TI  - P4-mediated antibody therapy in an acute model of invasive pneumococcal disease.
AB  - New treatments against severe bacterial infections are needed because the
      response to antibiotic treatment is slow in acute settings and is becoming less
      effective owing to the emergence of antibiotic-resistant pathogens. P4-mediated
      antibody therapy offers a unique treatment strategy that combines exogenous
      immunoglobulin with the immunoactivating peptide P4. In an acute model of
      pneumococcal disease, mice were infected with Streptococcus pneumoniae and
      treated intravenously or intranasally with P4 and intravenous immunoglobulin
      (IVIG). Survival of P4-IVIG-treated mice increased from 0% to 60% among those
      that received intravenous treatment and from 0% to 100% among those that received
      intranasal treatment. Importantly, intranasal administration of P4 at an early
      stage of infection prevented the onset of bacteremia and sepsis. Increased
      survival was associated with reduced bacterial burden in affected tissues and
      with recruitment and activation of professional phagocytes, as manifested by
      increased expression of Fc-gamma receptors. In vitro studies involving P4
      stimulated alveolar, peritoneal, and J774.2 murine macrophages showed an
      increased ability of these immune cells to phagocytose pneumococci independent of
      capsule. The use of adjunct antibody therapies to treat infectious diseases shows
      promise.

PMID- 22457295
TI  - Specific T cells restore the autophagic flux inhibited by Mycobacterium
      tuberculosis in human primary macrophages.
AB  - BACKGROUND: Autophagy inhibits survival of intracellular Mycobacterium
      tuberculosis when induced by rapamycin or interferon gamma (IFN-gamma), but it
      remains unclear whether M. tuberculosis itself can induce autophagy and whether T
      cells play a role in M. tuberculosis-mediated autophagy. The aim of this study
      was to evaluate the impact of M. tuberculosis on autophagy in human primary
      macrophages and the role of specific T cells in this process. METHODS: M.
      tuberculosis (H37Rv)-infected macrophages were incubated with naive or M.
      tuberculosis-specific T cells. Autophagy was evaluated at 4 hours and 8 hours
      after infection by analyzing the levels of LC3-II (a hallmark of autophagy) and
      p62 (a protein degraded by autophagy). M. tuberculosis survival was evaluated by
      counting the colony-forming units. RESULTS: M. tuberculosis infection of
      macrophages inhibited the autophagic process at 8 hours after infection. Naive T
      cells could not rescue this block, whereas M. tuberculosis-specific T cells
      restored autophagy degradation, accompanied by enhanced bacterial killing.
      Notably, the effect of M. tuberculosis-specific T cells was not affected by
      neutralization of endogenous IFN-gamma and tumor necrosis factor alpha and was
      blocked by preventing contact between macrophages and T cells, suggesting that
      cell-cell interaction is crucial. CONCLUSIONS: M. tuberculosis inhibits autophagy
      in human primary macrophages, and specific T cells can restore functional
      autophagic flux through cell-cell contact.

PMID- 22457296
TI  - High-quality meta-analyses are required for development of evidence in medicine.

PMID- 22457297
TI  - Investing in improved performance of national tuberculosis programs reduces the
      tuberculosis burden: analysis of 22 high-burden countries, 2002-2009.
AB  - OBJECTIVE: To assess the impact of investment in national tuberculosis programs
      (NTPs) on NTP performance and tuberculosis burden in 22 high-burden countries, as
      determined by the World Health Organization (WHO). DATA SOURCE/STUDY SETTING:
      Estimates of annual tuberculosis burden and NTP performance indicators and
      control variables during 2002-2009 were obtained from the Organization for
      Economic Cooperation and Development, the WHO, the World Bank, and the Penn World
      Table for the 22 high-burden countries. STUDY DESIGN: Panel data analysis was
      performed using the outcome variables tuberculosis incidence, prevalence, and
      mortality and the key explanatory variables Partnership case detection rate and
      treatment success rate, controlling for gross domestic product per capita,
      population structure, and human immunodeficiency virus (HIV) prevalence. RESULTS:
      A $1 per capita (general population) higher NTP budget (including domestic and
      external sources) was associated with a 1.9% (95% confidence interval, .12%-3.6%)
      higher estimated case detection rate the following year for the 22 high-burden
      countries between 2002 and 2009. In the final models, which corrected for
      autocorrelation and heteroskedasticity, achieving the STOP TB Partnership case
      detection rate target of >70% was associated with significantly (P < .01) lower
      tuberculosis incidence, prevalence, and mortality the following year, even when
      controlling for general economic development and HIV prevalence as potential
      confounding variables. CONCLUSIONS: Increased investment in NTPs was
      significantly associated with improved performance and with a downward trend in
      the tuberculosis burden in the 22 high-burden countries during 2002-2009.

PMID- 22457298
TI  - Adjunct immunotherapies for tuberculosis.
AB  - The continued spread of multidrug-resistant (MDR) tuberculosis and extensively
      drug-resistant tuberculosis poses a major threat to global tuberculosis control.
      Treatment is complex and requires longer use of more-expensive, less effective,
      and toxic anti-tuberculosis drugs, which results in high morbidity and mortality.
      The poor treatment outcomes and the slow progress in the development and
      evaluation of new tuberculosis drugs have given rise to the development of
      adjunct immunotherapy. The host immune system is a critical factor both for
      containment and cure of Mycobacterium tuberculosis infection. Augmentation or
      dampening of proinflammatory responses can be of value in the treatment of
      individuals who have nonproductive M. tuberculosis infection with inflammation
      induced tissue damage. The use of immunotherapy with interleukin 2, interferon
      gamma, and interleukin 7 as an adjunct to drug treatment may improve success
      rates for treatment of MDR tuberculosis, shorten treatment time for drug
      sensitive tuberculosis, and improve the immunity of individuals by enhancing M.
      tuberculosis elimination to prevent recurrence of disease. A broad range of
      immunological treatments, including cytokine treatment or cell-based therapy, is
      now available, although not all have been evaluated in humans. This review gives
      a critical overview of current adjunct immunotherapies for active tuberculosis,
      which are at various stages of development.

PMID- 22457299
TI  - VEnous INtervention (VEIN) 3 project: introduction.

PMID- 22457300
TI  - Epidemiology, risk factors and sequelae of venous thromboembolism.
AB  - The aim of this review was to discuss the epidemiology, risk factors and sequelae
      of venous thromboembolism (VTE). VTE has an incidence of 1-2 per 1000 people
      annually. The risk of VTE increases with age and is highest in Caucasians and
      African Americans. Combined oral contraceptives (COC), especially the third
      generation COCs, have been strongly implicated in VTE. Hospitalized patients,
      especially patients with underlying malignancy and undergoing surgery, have a
      host of risk factors for VTE. Thrombophilia can predispose an individual to VTE
      but indiscriminate testing for thrombophilia in patients presenting with VTE is
      not indicated. VTE can have serious chronic sequelae in the form of post
      thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension
      (CTPH). The risk of PTS and CTPH is increased with recurrent deep vein thrombosis
      and pulmonary embolism, respectively. Mortality from VTE can be as high as 21.6%
      at one year. Patients who had an episode of VTE have a high risk of subsequent
      VTE and this risk is highest in patients who had a first VTE event associated
      with malignancy. A good understanding of the epidemiology and risk factors of VTE
      will enable the treating medical practitioners to identify patients at risk and
      administer appropriate VTE prophylaxis to prevent the long-term consequences of
      VTE.

PMID- 22457301
TI  - Thrombosis: simplified.
AB  - The devastating consequences of venous thromboembolism have forever provided the
      impetus to explore safe and effective treatment strategies. To date, the
      pathophysiology and mechanism of thrombosis have been extensively studied and
      details of new thrombophilic conditions are continually being discovered.
      Although there has been extensive research detailing various predispositions to
      thrombosis, uncertainties regarding their appropriate management continue. This
      review aims to highlight the various challenges involved in identifying those at
      risk; provide appropriate management options; and lastly present the current
      views on the development of new anticoagulants that are competing to replace the
      traditional agents.

PMID- 22457302
TI  - Primary prevention of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is the most common cause of preventable in-hospital
      mortality and all hospitalized patients should be VTE risk assessed. The VTE risk
      should be weighed up against risk of bleeding on an individualized basis to guide
      choice of prophylaxis. The most common method of mechanical thromboprophylaxis is
      graduated compression stockings, although others, such as intermittent pneumatic
      devices, are available. Stockings have the greatest benefit when used in
      combination with pharmacological prophylaxis. However, stockings are
      contraindicated in some patients, including those with stroke or peripheral
      arterial disease. Various options for pharmacological thromboprophylaxis are
      available. The most commonly used agents are the low-molecular-weight heparins,
      but newer orally active agents may play an increasing role in the future.

PMID- 22457303
TI  - Pathways for venous thromboembolic prophylaxis in medical and surgical patients.
AB  - Despite the fact that venous thromboembolism (VTE) is one of the most widely
      studied areas in medicine, and despite the availability of data from numerous
      RCTs, there are many areas where the evidence is insufficient to allow grade A
      recommendations to be made. In these areas published guidelines often differ in
      their advice. In this chapter we primarily discuss the National Institute of
      Clinical and Health Excellence (NICE) VTE prophylaxis pathways in the context of
      other guidance published by the Scottish Intercollegiate Guideline Network and
      the American Colleges of Physicians and Chest Physicians. Evidence for the use of
      both mechanical and pharmacological thromboprophylaxis is discussed for both
      medical and surgical patients.

PMID- 22457304
TI  - Diagnostic tests and strategies in venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a term including deep vein thrombosis (DVT) and
      pulmonary embolism (PE). Timely and accurate diagnosis of both is essential as
      delayed or missed diagnoses can result in death or longer term complications.
      Patients with suspected DVT should initially undergo a pretest probability Wells
      score. Depending on pretest probability Wells score they should then either
      proceed to two-point ultrasound scanning or D-dimer testing. Likewise, patients
      suspected of PE should undergo a two-level PE Wells score, and, if scored likely,
      a computed tomography pulmonary angiogram (CTPA), or, if there is a low pretest
      probability score, D-dimer testing. If positive, patients should undergo CTPA.
      Ventilation perfusion scanning (V/Q scan) or V/Q SPECT should be considered in
      place of CTPA if there is allergy to contrast media or renal impairment.

PMID- 22457305
TI  - Cancer-related venous thromboembolic disease: current management and areas of
      uncertainty.
AB  - The relationship between cancer and venothromboembolic events is a complex,
      multifactorial process which is still not fully understood and therefore the use
      of current generic guidelines may be inadequate. Current management of cancer
      related VTE may be suboptimal because of the lack of cancer-specific studies into
      the role of primary prophylaxis in both ambulant and non-ambulant cancer
      patients. Further research into developing cancer-specific risk assessment tools
      and the choice, dose and duration of prophylaxis is required. The management of
      confirmed symptomatic VTE in cancer patients is outlined but certain
      controversies remain. Areas for further research include the management of
      asymptomatic unsuspected VTE events, recurrent VTE events on treatment and the
      role of IVC filters and other treatment options are required. This paper attempts
      to cover some of the recent developments and areas of uncertainty surrounding the
      management of cancer-related VTE.

PMID- 22457306
TI  - Management of proximal deep vein thrombosis.
AB  - Iliofemoral DVT constitutes approximately 20-25% of lower limb DVT and represents
      a specific subgroup of patients at highest risk for post-thrombotic syndrome
      (PTS). Anticoagulation alone has no significant thrombolytic activity and has not
      impact on PTS prevention. Early thrombus removal has reduced PTS in uncontrolled
      reports and reviews but major trials are awaited. The optimal timing for
      treatment appear to be thrombus <2 weeks old and, methods for thrombus removal
      include direct open or suction thrombectomy, catheter directed thrombolysis
      (CDT), with or without percutaneous mechanical thrombectomy (PMT) devices. Three
      principle types of PMT device are in use (rotational, rheolytic and ultrasound
      enhanced devices) and are combined with CDT in pharmocomechanical thrombolysis
      (PhMT) to enhance early thrombus removal. These devices have individual device
      specific attributes and side effects that are additional to the bleeding
      complications of thrombolysis. A number of additional interventions may be
      utilised to the improve results of CDT and PhMT. IVC filter deployment to reduce
      periprocedural PE, is supported by little evidence unless an indication for its
      use already exists. However, balloon venoplasty and vein stents undoubtedly vein
      patency after treatment. Early thrombus removal comes with additional upfront
      costs derived from devices, imaging and critical care bed usage. However,
      significant potential savings from reduction in PTS and rethrombosis rates may
      reduce overall societal costs. This review focuses on iliofemoral thrombosis,
      however, the less commonly encountered but clinically important subclavian vein
      thrombosis is also discussed.

PMID- 22457307
TI  - Pregnancy-associated venous thrombosis.
AB  - Pregnant women are at an increased risk of venous thromboembolism (VTE) and the
      consequences of an acute event in pregnancy can be debilitating, long-lasting or
      fatal. Screening for risk factors early in pregnancy and the provision of
      thromboprophylaxis are useful ways of preventing VTE in some women, but even when
      performed diligently, acute events are likely to remain common for the
      foreseeable future. It is therefore important for obstetric and non-obstetric
      clinicians to recognize the symptoms and signs of deep vein thrombosis and
      pulmonary embolism in pregnancy, to understand how a diagnosis can be reached in
      an effective yet safe manner and to be aware of the available treatment
      modalities.

PMID- 22457308
TI  - Venous thromboembolism in the paediatric patient.
AB  - Venous thromboembolism is a concern in the paediatric population and its
      incidence seems to be increasing. Symptoms and signs may be subtle so a high
      degree of suspicion is needed. Paediatric patients represent a unique challenge
      in the provision of anticoagulation due to their unique physiology.

PMID- 22457309
TI  - Class 1 integron-associated spread of resistance regions in Pseudomonas
      aeruginosa: plasmid or chromosomal platforms?

PMID- 22457310
TI  - VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa causing an outbreak
      in South Africa.

PMID- 22457312
TI  - Target gene mutations among methicillin-resistant Staphylococcus aureus and
      methicillin-susceptible S. aureus with elevated MICs of enrofloxacin obtained
      from diseased food-producing animals or food of animal origin.

PMID- 22457311
TI  - The 2011 Garrod Lecture: From penicillin-binding proteins to molecular
      epidemiology.
AB  - In this review, based on my Garrod Lecture to the British Society for
      Antimicrobial Chemotherapy, I have given a brief outline of my career over the
      past 40 years, starting with research in the 1970s into the properties and
      functions of penicillin-binding proteins (PBPs), leading to the identification of
      the high molecular mass PBPs as the physiological targets of penicillin, and
      subsequent studies showing the emergence of low-affinity PBPs in penicillin
      resistant clinical isolates by inter-species recombination and the generation of
      mosaic PBP genes. The studies of clinical isolates of gonococci, meningococci and
      pneumococci with PBP-mediated resistance to penicillin led to new interests in
      molecular epidemiology and the population and evolutionary biology of bacterial
      pathogens. The development (with colleagues) of multilocus sequence typing
      provided a method for the unambiguous characterization of bacterial strains that
      has proved to be very widely used, but the recent remarkable (and ongoing)
      developments in DNA sequencing technologies have provided the prospect of being
      able routinely to use whole genome sequences to characterize pathogen isolates.
      These developments will soon have major implications for diagnostic microbiology,
      outbreak investigations and our ability to follow the spread of strains of
      community-acquired and nosocomial pathogens at local, national and international
      levels. However, there are major barriers to be overcome, particularly with
      respect to how the avalanche of genome sequence data will be stored so that its
      transformative potential for molecular epidemiology and international public
      health are fully realized.

PMID- 22457313
TI  - Pharmacokinetics of doripenem in CSF of patients with non-inflamed meninges.
AB  - OBJECTIVES: To investigate intact blood-brain barrier (BBB) penetration by
      doripenem and characterize doripenem pharmacokinetics in CSF using a
      pharmacokinetic model. PATIENTS AND METHODS: Thirty-eight neurological patients
      with no active neurological disease or CNS infection received a single 500 mg
      doripenem dose before pump implantation surgery, or lumbar puncture, for
      intrathecal baclofen administration. In most cases single CSF and blood samples
      were collected per patient and analysed for doripenem with HPLC. A two-stage
      pharmacokinetic analysis was performed to estimate: (i) empirical Bayesian
      estimates (EBEs) of individual doripenem plasma pharmacokinetic parameters, using
      plasma doripenem concentrations and literature population priors for a two
      compartment model; and (ii) doripenem CSF pharmacokinetic parameters using
      simulated plasma concentrations from stage (i) as a forcing function. The mean
      values of the structural model parameters, k(CSF) (distribution rate constant)
      and PC (CSF/plasma partition coefficient), and the residual variability were
      estimated. RESULTS: The mean estimates of the parameters were k(CSF)= 0.105 h(-1)
      and PC= 0.053, corresponding to mean steady-state doripenem CSF concentrations of
      0.20 mg/L and 0.40 mg/L for regimens of 3 * 500 mg daily and 3 * 1000 mg daily,
      respectively, and a mean equilibrium half-life of 6.6 h. The model was validated
      internally using a visual predictive check (VPC) and bootstrap. Simulating two
      dosing scenarios gave doripenem levels in the CSF above or close to the
      literature MIC values. CONCLUSIONS: The present NONMEM software analysis shows
      that doripenem crosses intact BBB significantly and suggests that the drug should
      be further evaluated as a candidate to treat certain CNS infections, since drug
      penetration through BBB is enhanced by meningeal inflammation.

PMID- 22457314
TI  - Prevalence of HIV among men who have sex with men in Chongqing, China, 2006-2009:
      cross-sectional biological and behavioural surveys.
AB  - OBJECTIVE: To assess the prevalence of HIV among men who have sex with men (MSM)
      in Chongqing, China from 2006 to 2009. METHODS: The authors used a snowball
      sampling method to perform a 3-month cross-sectional study each year from 2006 to
      2009. Every participant was asked to complete a questionnaire about demographic
      and behavioural characteristics, and blood samples were taken for antibody
      testing for HIV and syphilis. RESULTS: A total of 953, 1015, 743 and 603
      participants were investigated in 2006, 2007, 2008 and 2009, respectively. HIV
      prevalence rates were 10.9%, 12.8%, 10.6% and 19.1%, respectively. The rates
      increased by 2.3% averagely per year (p<0.001). The HIV prevalence rates were
      significantly higher than the total population in subjects who were aged more
      than 40 years, subjects with an educational background of a junior high school
      level or lower, subjects with a positive syphilis infection or subjects who were
      recruited from a public bath (p<0.01). The HIV prevalence rates increased on
      average per year more than 4% in subjects over 30, subjects who worked in the
      entertainment business, subjects who were married or divorced, subjects with a
      positive syphilis infection or subjects who were not informed HIV test results.
      Although most subjects had good HIV/AIDS knowledge awareness (90%), the rate of
      consistent condom use was low (<37%). CONCLUSIONS: The prevalence of HIV is high
      and is rapidly growing among MSM in Chongqing, China. More appropriate responses
      are urgently needed to promote a change in the behaviour of MSM.

PMID- 22457315
TI  - Acceptability of providing self-taken vaginal samples and allowing access to NHS
      numbers and medical records: feasibility study in young female genitourinary
      medicine clinic attenders.

PMID- 22457316
TI  - Troponin-positive chest pain with unobstructed coronary arteries: definitive
      differential diagnosis using cardiac MRI.
AB  - OBJECTIVE: The purpose of this study was to assess the outcome of cardiac MRI
      (CMRI) with late gadolinium enhancement (LGE) at outpatient follow-up in a
      consecutive series of patients with troponin-positive chest pain but unobstructed
      coronary arteries at the index admission. METHODS: The study group comprised 91
      consecutive patients who presented to our institution with cardiac chest pain,
      elevated troponin I and unobstructed coronary arteries on coronary angiography.
      All patients underwent an outpatient CMRI with LGE imaging in order to establish
      a definitive diagnosis. RESULTS: The average time from coronary angiography to
      LGE-CMRI was 2 months. 73% of patients had no abnormality on their LGE-CMRI, 16%
      of patients had patchy late enhancement consistent with myocarditis and 11% had
      focal subendocardial or full thickness late enhancement consistent with
      myocardial infarction. There were no deaths in this cohort during a mean follow
      up of 21 months. CONCLUSION: LGE-CMRI is a useful tool for establishing whether
      such patients have definitive evidence of non-ST-segment elevation myocardial
      infarction (NSTEMI), and can make an important contribution to the long-term
      management strategy of these patients as an inappropriate diagnosis of NSTEMI
      carries important medical, social and financial implications.

PMID- 22457317
TI  - Simultaneous irradiation of the breast and regional lymph nodes in prone position
      using helical tomotherapy.
AB  - OBJECTIVE: We investigated dosimetric advantages of using helical tomotherapy to
      simultaneously irradiate the breast and regional lymph nodes for patients
      positioned prone, and compared tomotherapy plan qualities for the prone position
      with those previously published for the supine position. METHODS: Tomotherapy
      plans for 11 patients (5 left breast, 6 right) simulated with the involved breast
      suspended downward were generated. Each target (ipsilateral breast and
      supraclavicular, axillary and internal mammary chain nodes) was to receive 45 Gy.
      RESULTS: For targets, V(40.5)>=99.9% and V(42.8)>=99.5% for all patients, where
      V(40.5) and V(42.8) denote the relative target volume receiving at least 40.5 and
      42.8 Gy, respectively. The targets' maximum dose was, on average, approximately
      49.5 Gy. The mean doses to the contralateral lung and heart were lower for right
      breast cases (2.8 Gy lung, 2.7 Gy heart) than for left-breast cases (3.8 Gy lung,
      8.7 Gy heart). Mean organ doses to the ipsilateral lung (9.3 Gy) and
      contralateral breast (2.3 Gy) from the prone breast tomotherapy plans were
      similar to those reported for conventional radiotherapy techniques. For the left
      breast with regional nodes, tomotherapy plans for prone-positioned patients
      yielded lower mean doses to the contralateral breast and heart than previously
      reported data for tomotherapy plans for supine-positioned patients. CONCLUSION:
      Helical tomotherapy with prone breast positioning can simultaneously cover the
      breast and regional nodes with acceptable uniformity and can provide reduced mean
      dose to proximal organs at risk compared with tomotherapy with supine position.
      The similarity of plan quality to existing data for conventional breast
      radiotherapy indicates that this planning approach is appropriate, and that the
      risk of secondary tumour formation should not be significantly greater.

PMID- 22457318
TI  - Radiobiologically guided optimisation of the prescription dose and fractionation
      scheme in radiotherapy using BioSuite.
AB  - OBJECTIVE: Radiobiological models provide a means of evaluating treatment plans.
      Keeping in mind their inherent limitations, they can also be used prospectively
      to design new treatment strategies which maximise therapeutic ratio. We propose
      here a new method to customise fractionation and prescription dose. METHODS: To
      illustrate our new approach, two non-small cell lung cancer treatment plans and
      one prostate plan from our archive are analysed using the in-house software tool
      BioSuite. BioSuite computes normal tissue complication probability and tumour
      control probability using various radiobiological models and can suggest
      radiobiologically optimal prescription doses and fractionation schemes with
      limited toxicity. RESULTS: Dose-response curves present varied aspects depending
      on the nature of each case. The optimisation process suggests doses and
      fractionation schemes differing from the original ones. Patterns of optimisation
      depend on the degree of conformality, the behaviour of the normal tissue (i.e.
      "serial" or "parallel"), the volume of the tumour and the parameters of clonogen
      proliferation. CONCLUSION: Individualising the prescription dose and number of
      fractions with the help of BioSuite results in improved therapeutic ratios as
      evaluated by radiobiological models.

PMID- 22457319
TI  - Bone metastases from prostate, breast and multiple myeloma: differences in lesion
      conspicuity at short-tau inversion recovery and diffusion-weighted MRI.
AB  - OBJECTIVES: The objective of this study was to compare the relative conspicuity
      of bone metastases on short-tau inversion recovery (STIR) and diffusion-weighted
      MRI (DWI) whole-body MR sequences for breast, prostate and myeloma malignancies.
      METHODS: 44 whole-body MRI scans were reviewed retrospectively (coronal T(1)
      weighted, STIR and DWI with b=800). On each scan, up to four of the largest bone
      lesions were identified on T(1) weighting, and the region of interest signal
      intensity was measured on STIR and DWI, as well as the background signal
      intensity. The mean lesion signal to background ratio was calculated for each
      patient and then for each malignancy group. RESULTS: In prostate cancer patients,
      the DWI signal/background ratio was greater than that of STIR in 22 out of 24
      patients (mean DWI lesion/background ratio 3.91, mean STIR lesion/background
      ratio 2.31; p=0.0001). In multiple myeloma, the DWI ratio was higher in 6/7
      patients (DWI group mean ratio 7.59, STIR group mean ratio 3.7; p=0.0366). In 13
      breast cancer patients, mean STIR and DWI signal/background were similar (DWI
      group mean ratio 4.13, group mean STIR ratio 4.26; p=0.8587). CONCLUSION: Bone
      lesion conspicuity measured by lesion/background signal intensity was higher on
      DWI b=800 than on STIR in patients with prostate cancer and multiple myeloma. DWI
      should be used in whole-body MR oncology protocols in these conditions to
      maximise lesion detection.

PMID- 22457321
TI  - The efficacy and safety of degarelix, a GnRH antagonist: a 12-month, multicentre,
      randomized, maintenance dose-finding phase II study in Japanese patients with
      prostate cancer.
AB  - OBJECTIVE: To assess the efficacy and safety of degarelix, a new gonadotropin
      releasing hormone antagonist, for achieving and maintaining serum testosterone
      suppression (<=0.5 ng/ml) during the 12-month treatment of Japanese patients with
      prostate cancer. METHODS: This Phase II study was conducted as a multicentre,
      randomized, parallel-group, open-label study. A total of 273 patients with
      adenocarcinoma of the prostate (any stage) were treated. Degarelix was
      administered subcutaneously at an initial dose of 240 mg followed by monthly
      maintenance doses of either 80 or 160 mg for a total of 12 doses. The treatment
      continued for 12 months. RESULTS: Dose regimens of 240/80 and 240/160 mg
      maintained castrate levels of testosterone in 94.5 and 95.2% of the patients,
      respectively. After 3 days, 99.3 and 98.5% of the patients, respectively, reached
      these levels without a testosterone surge. Prostate-specific antigen levels
      decreased rapidly following degarelix administration and remained low throughout
      the study. Best overall response rates according to RECIST were 71.4 (20/28) and
      72.7% (16/22), respectively. Eighteen patients (6.6%) withdrew from the study due
      to adverse events. The most common adverse events were injection site reactions;
      other adverse events included hot flush, nasopharyngitis, weight increase and
      pyrexia. CONCLUSIONS: Both monthly degarelix dosing regimens were found to be
      effective in testosterone suppression without a testosterone surge, prostate
      specific antigen reductions and anti-tumour effect in Japanese patients with
      prostate cancer, as was shown in the overseas Phase III study. Degarelix was also
      well tolerated.

PMID- 22457320
TI  - Stress cardiovascular MR in routine clinical practice: referral patterns,
      accuracy, tolerance, safety and incidental findings.
AB  - OBJECTIVE: The use of stress cardiovascular MR (CMR) to evaluate myocardial
      ischaemia has increased significantly over recent years. We aimed to assess the
      indications, incidental findings, tolerance, safety and accuracy of stress CMR in
      routine clinical practice. METHODS: We retrospectively examined all stress CMR
      studies performed at our tertiary referral centre over a 20-month period.
      Patients were scanned at 1.5 T, using a standardised protocol with routine
      imaging for late gadolinium enhancement. Angiograms of patients were assessed by
      an interventional cardiologist blinded to the CMR data. RESULTS: 654 patients
      were scanned (mean age 65+/-29 years; 63 inpatients; 9.6%). 14% of patients had
      incidental extracardiac findings, the commonest being liver or renal cysts (6%)
      and pulmonary nodules (4%). 639 patients (97.7%) received intravenous adenosine,
      10 received intravenous dobutamine and 5 patients had both. Of the 15 patients
      who received dobutamine, 12 had no side-effects/complications, 2 experienced
      nausea and 1 chest tightness. Of the 644 patients who received adenosine, 43%
      experienced minor symptoms, 1% had transient heart block and 0.2% had severe
      bronchospasm requiring termination of infusion. There were no cases of
      hospitalisation or myocardial infarction. 241 patients also had coronary
      angiography. For detecting at least moderate stenosis of >=50%, sensitivity was
      86%, specificity 98% and accuracy 89%. For detecting severe stenoses of >=70%,
      sensitivity was 91%, specificity 86% and overall accuracy 90%. These results
      compare very favourably with previous smaller research studies and meta-analyses.
      CONCLUSION: We conclude that stress CMR, with adenosine as the main stress agent,
      is well tolerated, safe and accurate in routine clinical practice.

PMID- 22457322
TI  - Physician preferences and knowledge regarding the care of childhood cancer
      survivors in Japan: a mailed survey of the Japanese Society of Pediatric
      Oncology.
AB  - OBJECTIVE: Japanese physicians' attitudes regarding the health-care needs of
      young adult childhood cancer survivors (CCSs) are not well described. Thus, we
      examined the self-reported preferences and knowledge of pediatric oncologists and
      surgeons. METHODS: A mailed survey was sent to 858 physician members of the
      Japanese Society of Pediatric Oncology. We compared the responses of pediatric
      oncologists and pediatric surgeons. RESULTS: The pediatric oncologists' response
      rate was 56% (300 out of 533) and that of pediatric surgeons 32% (105 out of
      325). The median age of respondents was 46 and 48 years, respectively; 79 and 84%
      were men. When comfort levels in caring for CCSs were described (i.e. 1 = very
      uncomfortable; 7 = very comfortable), the mean levels were 4.4 and 3.8 with CCSs
      <= 21 years, 3.6 and 3.6 with 21 years < CCSs <= 30 years, and 2.8 and 3.3 with
      CCSs > 30 years, respectively. In clinical vignette questions, 62% of the
      pediatric oncologists and 43% of the surgeons answered three or more questions
      appropriately. Pediatric surgeons reported significantly lower familiarity with
      long-term follow-up guidelines than pediatric oncologists. Most pediatric
      oncologists and many surgeons conducted truth-telling of cancer diagnosis to
      adult CCSs now. They thought that the most important issues are an original long
      term follow-up guideline suitable for the Japanese situation and collaborations
      with adult-based general physicians. CONCLUSIONS: Many Japanese pediatric
      oncologists are uncomfortable with caring for survivors as they age and have
      suboptimal knowledge regarding late effects. The change in truth-telling
      situation and preference for collaboration with adult-based physicians was
      demonstrated also in Japan.

PMID- 22457324
TI  - Oncology information on the Internet.
AB  - Owing to new developments in Internet technologies, the amount of available
      oncology information is growing. Both patients and caregivers are increasingly
      using the Internet to obtain medical information. However, while it is easy to
      provide information, ensuring its quality is always a concern. Thus, many
      instruments for evaluating the quality of health information have been created,
      each with its own advantages and disadvantages. The increasing importance of
      online search engines such as Google warrants the examination of the correlation
      between their rankings and medical quality. The Internet also mediates the
      exchange of information from one individual to another. Mailing lists of advocate
      groups and social networking sites help spread information to patients and
      caregivers. While text messages are still the main medium of communication, audio
      and video messages are also increasing rapidly, accelerating the communication on
      the Internet. Future health information developments on the Internet include
      merging patients' personal information on the Internet with their traditional
      health records and facilitating the interaction among patients, caregivers and
      health-care providers. Through these developments, the Internet is expected to
      strengthen the mutually beneficial relationships among all stakeholders in the
      field of medicine.

PMID- 22457323
TI  - Clinical impact of switching to a second EGFR-TKI after a severe AE related to a
      first EGFR-TKI in EGFR-mutated NSCLC.
AB  - OBJECTIVE: Somatic mutations in the epidermal growth factor receptor gene are
      associated with a therapeutic response to epidermal growth factor receptor
      tyrosine kinase inhibitors such as gefitinib and erlotinib in patients with non
      small cell lung cancer. Although the safety profile of these drugs is favorable,
      a small proportion of patients with EGFR mutation-positive non-small cell lung
      cancer must discontinue treatment because of adverse events such as interstitial
      lung disease and hepatotoxicity. Subsequent chemotherapy has not been optimized
      in such patients. METHODS: We performed a retrospective analysis of EGFR mutation
      positive non-small cell lung cancer patients who received both gefitinib and
      erlotinib at our institution. Patients received the second epidermal growth
      factor receptor-tyrosine kinase inhibitor after experiencing an adverse event or
      progressive disease on the first epidermal growth factor receptor-tyrosine kinase
      inhibitor. RESULTS: We identified 14 patients who received both gefitinib and
      erlotinib in the course of their treatment. Three patients initially treated with
      gefitinib and two with erlotinib discontinued epidermal growth factor receptor
      tyrosine kinase inhibitor therapy because of severe non-hematologic toxicity (one
      because of gefitinib-induced interstitial lung disease, one because of erlotinib
      induced lupus erythematosus-like eruption and three because of hepatotoxicity).
      All five of these patients were able successfully to continue therapy with the
      second epidermal growth factor receptor-tyrosine kinase inhibitor with no
      evidence of a recurrent adverse event. Progression-free survival was
      significantly longer in these five patients than in the nine patients who
      discontinued treatment with the first epidermal growth factor receptor-tyrosine
      kinase inhibitor because of disease progression. CONCLUSIONS: EGFR mutation
      positive non-small cell lung cancer patients who discontinue treatment with a
      first epidermal growth factor receptor-tyrosine kinase inhibitor because of an
      adverse event benefit substantially from switching to a second epidermal growth
      factor receptor-tyrosine kinase inhibitor before the development of drug
      resistance.

PMID- 22457325
TI  - Prediction of lateral lymph node metastasis in lower rectal cancer: analysis of
      paraffin-embedded sections.
AB  - OBJECTIVE: In the surgical treatment for lower rectal cancer, preoperative
      selection of patients at high risk for lateral lymph node metastasis is
      important, since lateral lymph node dissection might impair genitourinary
      functions. We examined whether the status of lateral lymph node metastasis can be
      predicted from the lymph node size. METHODS: The subjects were 533 (35 positive
      and 498 negative) lateral lymph nodes from 47 patients with lower rectal cancer
      who underwent curative resection with lateral lymph node dissection. The sizes of
      the lateral lymph nodes immediately after removal and those in paraffin-embedded
      sections were compared for 108 lateral lymph nodes from 13 patients. In addition,
      receiver-operating characteristic curves were generated for the 533 paraffin
      embedded lateral lymph nodes from the 47 patients to determine the optimal cut
      off size for discriminating between positive and negative lateral lymph nodes.
      RESULTS: Irrespective of the presence/absence of metastasis and the long-/short
      axis diameter, a positive relationship was noted between the sizes of the lateral
      lymph nodes measured immediately after removal and those measured on paraffin
      embedded sections (P< 0.01). The area under the curve for the short-axis diameter
      differed little from that for the long-axis diameter (0.77 vs. 0.76, P =0.80).
      The optimal cut-off values of the short- and long-axis diameter extrapolated to
      the living body were 5.4 and 8.4 mm, respectively, with an accuracy of 72.8% for
      the short-axis diameter and 71.9% for the long-axis diameter. CONCLUSIONS:
      Prediction of the status of lateral lymph node metastasis from the lymph node
      size (long-/short-axis diameter) may be a simple and reliable method. The optimal
      cut-off diameter should be validated in prospective imaging studies.

PMID- 22457327
TI  - Focus issue: TOR signaling, a tale of two complexes.
AB  - Through its association with two distinct protein complexes, target of rapamycin
      (TOR) complex 1 (TORC1) and TOR complex 2 (TORC2), the kinase TOR coordinates
      cellular growth with cell cycles, growth factors, and nutrients. The
      interconnected TOR signaling network participates in various physiological and
      pathophysiological conditions, such as aging, stem cell renewal, cell
      specification, and carcinogenesis; therefore, understanding the details of this
      system may yield new ways to promote longer, healthier living. This issue
      provides an overview of research on TOR signaling that has emerged since the
      issue Science Signaling devoted to this topic in 2009.

PMID- 22457326
TI  - Long-term oncological outcome and risk stratification in men with high-risk
      prostate cancer treated with radical prostatectomy.
AB  - OBJECTIVE: To evaluate the long-term oncological outcome of radical prostatectomy
      for patients with high-risk prostate cancer. METHODS: Among 378 patients with
      prostate cancer who underwent radical prostatectomy at our hospital, 189 had high
      risk prostate cancer defined as presenting with at least one of the following
      high-risk factors: prostate-specific antigen >20 ng/ml, clinical T3 and biopsy
      Gleason score >=8. RESULTS: The median follow-up was 8.1 years. Of all patients,
      106 and 61 had one and two high-risk factors, respectively, and the remaining 22
      had all three high-risk factors. Pathological examination of the prostatectomy
      specimens revealed organ-confined disease, specimen-confined disease and lymph
      node metastasis in 80 (42%), 102 (54%) and 22 (12%), respectively. The 10-year
      prostate-specific antigen failure-free and local progression-free survival rates
      were 48.5 and 87.6%, respectively. The 10-year cancer-specific and overall
      survival rates were 94.1 and 88.7%, respectively. The 10-year prostate-specific
      antigen failure-free survivals of patients with one, two and all three high-risk
      factors were 58.5, 39.9 and 22.7%, respectively (P = 0.0001). Of the 106 patients
      with one high-risk factor only, the high Gleason score group had the best 10-year
      prostate-specific antigen failure-free survival (69.1%); in particular, that of
      patients without Gleason grade 5 was 100% (P= 0.032). CONCLUSIONS: Approximately
      half of patients with high-risk prostate cancer can be cured by radical
      prostatectomy without any adjuvant treatment. Radical prostatectomy for high-risk
      prostate cancer provides good long-term local cancer control and cancer-specific
      survival. In particular, radical prostatectomy for patients with only one high
      risk factor can be considered a valuable therapeutic option as the first
      treatment.

PMID- 22457328
TI  - Deconvolution of mTORC2 "in Silico".
AB  - The protein kinase mTOR (mammalian or mechanistic target of rapamycin)
      coordinates a complex signal transduction network. By assembling with unique and
      shared partner proteins, mTOR forms the catalytic core of at least two complexes,
      mTOR complex 1 (mTORC1) and mTORC2, that show differential sensitivity to the
      allosteric mTOR inhibitor rapamycin and that phosphorylate distinct substrates to
      modulate cell growth, proliferation, survival, and metabolism in response to
      diverse environmental cues. Understanding mTOR network circuitry will provide
      insight into how its deregulation contributes to pathologic states such as
      diabetes, cancer, and cardiovascular disease. Research published in Science
      Signaling describes an investigation of the complex insulin-mTOR network by
      combining classic biochemical approaches with dynamic mathematical modeling in
      silico to elucidate how insulin activates mTORC2, an event that remains poorly
      defined.

PMID- 22457329
TI  - Phospholipase D and mTORC1: nutrients are what bring them together.
AB  - Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) plays a central role in
      translating nutrient abundance into cell growth and proliferation. Although
      specific proteins have been described as mediators of this nutrient input, their
      mechanistic linkage remains incomplete. Two studies have added phospholipase D
      (PLD) as a mediator of nutrients to mTORC1. Furthermore, these studies link PLD
      and its product phosphatidic acid to previously identified activators of mTORC1
      signaling, including the class III phosphoinositide-3 kinase, and provide
      evidence of the existence of two parallel nutrient-regulated pathways that
      converge on mTORC1 at late endosomes and/or lysosomes.

PMID- 22457330
TI  - Chronic activation of mTOR complex 1 is sufficient to cause hepatocellular
      carcinoma in mice.
AB  - The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a nutrient
      sensitive protein kinase that is aberrantly activated in many human cancers.
      Whether dysregulation of mTORC1 signaling in normal tissues increases the risk
      for cancer, however, is unknown. We focused on hepatocellular carcinoma, which
      has been linked to environmental factors that affect mTORC1 activity, including
      diet. Ablation of the gene encoding TSC1 (tuberous sclerosis complex 1), which as
      part of the TSC1-TSC2 complex is an upstream inhibitor of mTORC1, results in
      constitutively increased mTORC1 signaling, an effect on this pathway similar to
      that of obesity. We found that mice with liver-specific knockout of Tsc1
      developed sporadic hepatocellular carcinoma with heterogeneous histological and
      biochemical features. The spontaneous development of hepatocellular carcinoma in
      this mouse model was preceded by a series of pathological changes that accompany
      the primary etiologies of this cancer in humans, including liver damage,
      inflammation, necrosis, and regeneration. Chronic mTORC1 signaling led to
      unresolved endoplasmic reticulum stress and defects in autophagy, factors that
      contributed to hepatocyte damage and hepatocellular carcinoma development.
      Therefore, we conclude that increased activation of mTORC1 can promote
      carcinogenesis and may thus represent a key molecular link between cancer risk
      and environmental factors, such as diet.

PMID- 22457331
TI  - A dynamic network model of mTOR signaling reveals TSC-independent mTORC2
      regulation.
AB  - The kinase mammalian target of rapamycin (mTOR) exists in two multiprotein
      complexes (mTORC1 and mTORC2) and is a central regulator of growth and
      metabolism. Insulin activation of mTORC1, mediated by phosphoinositide 3-kinase
      (PI3K), Akt, and the inhibitory tuberous sclerosis complex 1/2 (TSC1-TSC2),
      initiates a negative feedback loop that ultimately inhibits PI3K. We present a
      data-driven dynamic insulin-mTOR network model that integrates the entire core
      network and used this model to investigate the less well understood mechanisms by
      which insulin regulates mTORC2. By analyzing the effects of perturbations
      targeting several levels within the network in silico and experimentally, we
      found that, in contrast to current hypotheses, the TSC1-TSC2 complex was not a
      direct or indirect (acting through the negative feedback loop) regulator of
      mTORC2. Although mTORC2 activation required active PI3K, this was not affected by
      the negative feedback loop. Therefore, we propose an mTORC2 activation pathway
      through a PI3K variant that is insensitive to the negative feedback loop that
      regulates mTORC1. This putative pathway predicts that mTORC2 would be refractory
      to Akt, which inhibits TSC1-TSC2, and, indeed, we found that mTORC2 was
      insensitive to constitutive Akt activation in several cell types. Our results
      suggest that a previously unknown network structure connects mTORC2 to its
      upstream cues and clarifies which molecular connectors contribute to mTORC2
      activation.

PMID- 22457333
TI  - The myth of Jocasta and maternal narcissism.
AB  - OBJECTIVE: This paper utilises the ancient Greek myth of Oedipus, and in
      particular the character's frequently overlooked mother Jocasta, to highlight
      some of the issues associated with maternal narcissism. CONCLUSIONS: A discussion
      of Jocasta forms the background to case studies where a mother's narcissism,
      along with an absent father, was pivotal to coping difficulties, which ultimately
      compelled the patient to seek therapy. Consideration of the Oedipus-Jocasta
      interpersonal dynamic can contribute to a greater understanding of these
      patients.

PMID- 22457332
TI  - Hyperplexing: a method for higher-order multiplexed quantitative proteomics
      provides a map of the dynamic response to rapamycin in yeast.
AB  - Large-scale quantitative proteomics can provide a near-global view of cellular
      protein abundance. Yet, the time, effort, and expertise required to achieve
      reasonable protein coverage and reliable quantification have limited the broad
      application of this technology. To fully leverage mass spectrometry for the
      elucidation of biological systems requires sufficient throughput to monitor
      dynamic changes across conditions and to enable replicate analysis to provide
      statistical power. We report a straightforward approach to increase the
      multiplexing capacity of quantitative mass spectrometry, which provides a
      platform for the analysis of cellular signaling pathways. Using triplex metabolic
      labeling and six-plex isobaric tags, we monitored changes in protein abundance
      from 18 samples simultaneously, performing biological triplicates of a six-point
      time course of rapamycin-stimulated yeast. The data set provides temporal
      abundance profiles for thousands of yeast proteins, highlighting the complex
      cellular roles of the TOR (target of rapamycin) pathway.

PMID- 22457334
TI  - Johann Christian Reil and the naming of our specialty.

PMID- 22457335
TI  - Pattern-based formulation: a methodology for psychiatric case formulation.
AB  - OBJECTIVE: Psychiatric formulation is often considered a challenging task,
      particularly for trainees and students in psychiatry. The process of arriving at
      a good psychiatric formulation involves identifying major issues of the patient,
      and developing an explanatory system, which can be derived using known
      theoretical models in psychiatry. A good explanatory system should provide a high
      degree of coherence by linking the most relevant data, justification for the
      proposed management plan, and its feasibility. Unfortunately, the literature on
      'how' to develop psychiatric formulation is limited, and for the trainees,
      psychiatric formulation remains a challenging task. METHOD: Based on the clinical
      reasoning strategy known as pattern recognition, a methodology for psychiatric
      case formulation has been proposed. The methodology uses a repository of
      templates, which are derived from major theoretical models in psychiatry.
      Developing a formulation involves a process of selecting, prioritising and
      combining templates according to the elicited set of main issues or
      psychopathology. The pattern resulting from the combination of different
      templates provides a degree of uniqueness to the explanatory system. CONCLUSION:
      It is expected that this methodology will help trainees and students to develop a
      broader understanding and skills in psychiatric formulation.

PMID- 22457336
TI  - Improving mental health awareness among rural Aboriginal men: perspectives from
      Gippsland.
AB  - OBJECTIVE: To identify views of Aboriginal people in rural areas about improving
      mental health awareness among Aboriginal men. METHOD: Semi-structured interviews
      were conducted with 17 Aboriginal people, including men, carers and health
      workers. RESULTS: Participants highlighted the need for mental health awareness
      programs in the community. They described the type of programs to be conducted as
      well as their method, content and frequency. CONCLUSIONS: This study demonstrates
      that mental health awareness programs designed specifically for rural Aboriginal
      men need to involve local Elders and other significant individuals from the
      community, be de-stigmatised by including mental health under Men's Health and by
      embedding the messages within a cultural framework.

PMID- 22457337
TI  - Lessons from an investigation of seclusion at an older adolescent inpatient unit.
AB  - OBJECTIVE: To determine the rate, indications and process for using seclusion for
      patients undergoing treatment at an older adolescent inpatient unit. METHOD: Data
      were gathered prospectively and retrospectively as part of a quality assurance
      initiative at the Christchurch Youth Inpatient Unit (YIU); paper, electronic and
      legal documentation were examined. RESULTS: During the time period of the
      investigation, approximately 13% of individuals admitted to the unit were
      secluded. Psychosis, involuntary admission and Maori ethnicity were significantly
      associated with the use of seclusion with aggression being the most documented
      indication. The vast majority of seclusions occurred within the first seven days
      of admission and over half utilized pro re nata medication prior to seclusion.
      CONCLUSIONS: Opportunities exist for intensifying and focusing efforts to
      minimize the use of seclusion and restraint, particularly during the first week
      of hospitalization.

PMID- 22457338
TI  - Dichotomizing continuous variables in statistical analysis: a practice to avoid.

PMID- 22457341
TI  - Visual performance feedback: effects on targeted and nontargeted staff.
AB  - This study used a multiple baseline with reversal design to assess whether visual
      performance feedback (VPF) influenced targeted and nontargeted staffs' use of
      behavior-specific praise (BSP) in a day-treatment program. This study expands on
      the typical VPF audience and assesses whether VPF can be effective with
      noncertified staff in a day-treatment program for young children with behavior
      disorders, an environment in which it is difficult to maintain high rates of BSP.
      In previous school-based studies, VPF has been collected by researchers and
      provided to targeted teaching staff. In the current study, rather than relying on
      researchers, the authors used staff instructors to collect VPF and assessed how
      that experience influenced the instructors' use of BSP. Results suggest that VPF
      provided, on average, a doubling in rates of BSP use by directly targeted staff
      and more than a 50% increase in rates of BSP in nontargeted instructors who
      collected BSP data. Furthermore, three of the four participants had substantially
      higher praise-to-correction ratios during the VPF intervention when compared with
      baseline and reversal conditions. Implications for improving treatment fidelity
      and reducing supervision time are discussed.

PMID- 22457342
TI  - Metaphoric language and the articulation of emotions by people affected by motor
      neurone disease.
AB  - OBJECTIVE: To explore the use of metaphoric language to convey emotion in
      interviews with people affected by motor neurone disease, a progressive
      neurological condition that sits between chronic and terminal illness. METHODS:
      Secondary analysis of 46 interviews with people affected by motor neurone disease
      in the United Kingdom (35 individuals with the condition, 11 carers). RESULTS:
      Metaphor and figurative language was used to communicate the intensely emotional
      experiences of being diagnosed with and living with motor neurone disease. We
      focus on three pervasive themes that were threaded throughout the interviews:
      battling and fighting; the self under attack and journeying through a physical
      and emotional landscape. DISCUSSION: This secondary analysis of qualitative
      research interviews enriches our understanding of the articulation of emotion in
      motor neurone disease and adds to the literature on metaphor in chronic illness.
      Of particular interest is how the metaphors used contrasted with other conditions
      in the relative absence of metaphors of 'fighting' the disease. Furthermore, we
      analyse the ways in which participants used metaphors to give voice to emotions
      that are extremely difficult to articulate in 'literal' language, and how, in
      doing so, they blurred the distinction between 'physical' symptoms and
      'emotional' states. Sensitivity to metaphors may help professionals communicate
      with people affected by motor neurone disease.

PMID- 22457343
TI  - A genome-wide association study in progressive multiple sclerosis.
AB  - BACKGROUND: The role played by genetic factors in influencing the clinical course
      of multiple sclerosis (MS) is not yet well established. OBJECTIVE: We aimed to
      identify genetic variants associated with progressive MS (PrMS). METHODS: We
      conducted a genome-wide association study (GWAS) in 197 patients with PrMS and
      234 controls of Italian origin. We tested the top 20 single nucleotide
      polymorphisms (SNPs) with suggestive evidence of association (p-value<10(-4)) in
      two independent sets of primary progressive MS cases and controls. RESULTS: We
      identified a risk-associated SNP in the HLA region in linkage disequilibrium (LD)
      with DRB1*1501 and DQB*0602 loci, with genome-wide significance (rs3129934(T), p
      (combined)=6.7*10(-16), OR=2.34, 95% CI=1.90-2.87), and a novel locus on
      chromosome 7q35 with suggestive evidence of association (rs996343(G), p
      (combined)=2.4*10(-5), OR=0.70, 95% CI=0.59-0.83) which maps within a human
      endogenous retroviral (HERV) element. The new locus did not have a 'cis' effect
      on RNA expression in lymphoblastic cell lines, but pathway analyses of 'trans'
      effects point to an expression regulation of genes involved in neurodegeneration,
      including glutamate metabolism (p<0.01) and axonal guidance signalling (p<0.02).
      CONCLUSIONS: We have confirmed the established association with the HLA region
      and, despite the low statistical power of the study, we found suggestive evidence
      for association with a novel locus on chromosome 7, with a putative regulatory
      role.

PMID- 22457344
TI  - A pilot study of the immunological effects of high-dose vitamin D in healthy
      volunteers.
AB  - Although vitamin D deficiency is considered an environmental factor in multiple
      sclerosis (MS), the immunological and clinical effects of vitamin D
      supplementation remain unclear. We performed a pilot study of the
      immunomodulatory effects of vitamin D in healthy individuals (n=4), who took 5000
      10,000 IU/day of vitamin D over 15 weeks. After 15 weeks of vitamin D
      supplementation, serum 25(OH) vitamin D levels rose significantly from baseline,
      with a corresponding increase in IL-10 production by peripheral blood mononuclear
      cells and a reduced frequency of Th17 cells. These data provide a strong
      rationale for randomised trials to assess the clinical effects of vitamin D
      supplementation in MS.

PMID- 22457345
TI  - Human endogenous retrovirus type W envelope expression in blood and brain cells
      provides new insights into multiple sclerosis disease.
AB  - BACKGROUND: The envelope protein from multiple sclerosis (MS) associated
      retroviral element (MSRV), a member of the Human Endogenous Retroviral family 'W'
      (HERV-W), induces dysimmunity and inflammation. OBJECTIVE: The objective of this
      study was to confirm and specify the association between HERV-W/MSRV envelope
      (Env) expression and MS. METHODS: 103 MS, 199 healthy controls (HC) and controls
      with other neurological diseases (28), chronic infections (30) or autoimmunity
      (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA
      copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a
      quantitative polymerase chain reaction (PCR). Env was detected by immunohistology
      in the brains of patients with MS with three specific monoclonals. RESULTS: Env
      antigen was detected in a serum of 73% of patients with MS with similar
      prevalence in all clinical forms, and not in chronic infection, systemic lupus,
      most other neurological diseases and healthy donors (p<0.01). Cases with chronic
      inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were
      positive. RNA expression in PBMC and DNA copy numbers were significantly elevated
      in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers
      were significantly increased in chronic progressive MS (secondary progressive MS
      vs relapsing-remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS -<0.02).
      Env protein was evidenced in macrophages within MS brain lesions with particular
      concentrations around vascular elements. CONCLUSION: The association between MS
      disease and the MSRV-type HERV-W element now appears quite strong, as evidenced
      ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions.
      Chronic progressive MS, RRMS and clinically isolated syndrome show different
      ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an
      increase with disease evolution, and amplicon sequencing confirms the association
      with particular HERV-W elements.

PMID- 22457346
TI  - Caudal-related homeobox (Cdx) protein-dependent integration of canonical Wnt
      signaling on paired-box 3 (Pax3) neural crest enhancer.
AB  - One of the earliest events in neural crest development takes place at the neural
      plate border and consists in the induction of Pax3 expression by posteriorizing
      Wnt.beta-catenin signaling. The molecular mechanism of this regulation is not
      well understood, but several observations suggest a role for posteriorizing Cdx
      transcription factors (Cdx1/2/4) in this process. Cdx genes are known as
      integrators of posteriorizing signals from Wnt, retinoic acid, and FGF pathways.
      In this work, we report that Wnt-mediated regulation of murine Pax3 expression is
      indirect and involves Cdx proteins as intermediates. We show that Pax3
      transcripts co-localize with Cdx proteins in the posterior neurectoderm and that
      neural Pax3 expression is reduced in Cdx1-null embryos. Using Wnt3a-treated P19
      cells and neural crest-derived Neuro2a cells, we demonstrate that Pax3 expression
      is induced by the Wnt-Cdx pathway. Co-transfection analyses, electrophoretic
      mobility shift assays, chromatin immunoprecipitation, and transgenic studies
      further indicate that Cdx proteins operate via direct binding to an
      evolutionarily conserved neural crest enhancer of the Pax3 proximal promoter.
      Taken together, these results suggest a novel neural function for Cdx proteins
      within the gene regulatory network controlling neural crest development.

PMID- 22457347
TI  - Impact of manganese on and transfer across blood-brain and blood-cerebrospinal
      fluid barrier in vitro.
AB  - Manganese occupational and dietary overexposure has been shown to result in
      specific clinical central nervous system syndromes, which are similar to those
      observed in Parkinson disease. To date, modes of neurotoxic action of Mn are
      still to be elucidated but are thought to be strongly related to Mn accumulation
      in brain and oxidative stress. However, the pathway and the exact process of Mn
      uptake in the brain are yet not fully understood. Here, two well characterized
      primary porcine in vitro models of the blood-brain and the blood-cerebrospinal
      fluid (CSF) barrier were applied to assess the transfer of Mn in the brain while
      monitoring its effect on the barrier properties. Thus, for the first time effects
      of MnCl(2) on the integrity of these two barriers as well as Mn transfer across
      the respective barriers are compared in one study. The data reveal a stronger Mn
      sensitivity of the in vitro blood-CSF barrier compared with the blood-brain
      barrier. Very interestingly, the negative effects of Mn on the structural and
      functional properties of the highly Mn-sensitive blood-CSF barrier were partly
      reversible after incubation with calcium. In summary, both the observed stronger
      Mn sensitivity of the in vitro blood-CSF barrier and the observed site-directed,
      most probably active, Mn transport toward the brain facing compartment, reveal
      that, in contrast to the general assumption in literature, after oral Mn intake
      the blood-CSF barrier might be the major route for Mn into the brain.

PMID- 22457348
TI  - Selective Galphai subunits as novel direct activators of transient receptor
      potential canonical (TRPC)4 and TRPC5 channels.
AB  - The ubiquitous transient receptor potential canonical (TRPC) channels function as
      non-selective, Ca(2+)-permeable channels and mediate numerous cellular functions.
      It is commonly assumed that TRPC channels are activated by stimulation of
      Galpha(q)-PLC-coupled receptors. However, whether the Galpha(q)-PLC pathway is
      the main regulator of TRPC4/5 channels and how other Galpha proteins may regulate
      these channels are poorly understood. We previously reported that TRPC4/TRPC5 can
      be activated by Galpha(i). In the current work, we found that Galpha(i) subunits,
      rather than Galpha(q), are the primary and direct activators of TRPC4 and TRPC5.
      We report a novel molecular mechanism in which TRPC4 is activated by several
      Galpha(i) subunits, most prominently by Galpha(i2), and TRPC5 is activated
      primarily by Galpha(i3). Activation of Galpha(i) by the muscarinic M2 receptors
      or expression of the constitutively active Galpha(i) mutants equally and fully
      activates the channels. Moreover, both TRPC4 and TRPC5 are activated by direct
      interaction of their conserved C-terminal SESTD (SEC14-like and spectrin-type
      domains) with the Galpha(i) subunits. Two amino acids (lysine 715 and arginine
      716) of the TRPC4 C terminus were identified by structural modeling as mediating
      the interaction with Galpha(i2). These findings indicate an essential role of
      Galpha(i) proteins as novel activators for TRPC4/5 and reveal the molecular
      mechanism by which G-proteins activate the channels.

PMID- 22457349
TI  - L-MPZ, a novel isoform of myelin P0, is produced by stop codon readthrough.
AB  - Myelin protein zero (P0 or MPZ) is a major myelin protein (~30 kDa) expressed in
      the peripheral nervous system (PNS) in terrestrial vertebrates. Several groups
      have detected a P0-related 36-kDa (or 35-kDa) protein that is expressed in the
      PNS as an antigen for the serum IgG of patients with neuropathy. The molecular
      structure and function of this 36-kDa protein are, however, still unknown. We
      hypothesized that the 36-kDa protein may be derived from P0 mRNA by stop codon
      readthrough. We found a highly conserved region after the regular stop codon in
      predicted sequences from the 3'-UTR of P0 in higher animals. MS of the 36-kDa
      protein revealed that both P0 peptides and peptides deduced from the P0 3'-UTR
      sequence were found among the tryptic fragments. In transfected cells and in an
      in vitro transcription/translation system, the 36-kDa molecule was also produced
      from the identical mRNA that produced P0. We designated this 36-kDa molecule as
      large myelin protein zero (L-MPZ), a novel isoform of P0 that contains an
      additional domain at the C terminus. In the PNS, L-MPZ was localized in compact
      myelin. In transfected cells, just like P0, L-MPZ was localized at cell-cell
      adhesion sites in the plasma membrane. These results suggest that L-MPZ produced
      by the stop codon readthrough mechanism is potentially involved in myelination.
      Since this is the first finding of stop codon readthrough in a common mammalian
      protein, detailed analysis of L-MPZ expression will help to understand the
      mechanism of stop codon readthrough in mammals.

PMID- 22457350
TI  - Calsequestrin accumulation in rough endoplasmic reticulum promotes perinuclear
      Ca2+ release.
AB  - Molecular mechanisms underlying Ca(2+) regulation by perinuclear
      endoplasmic/sarcoplasmic reticulum (ER/SR) cisternae in cardiomyocytes remain
      obscure. To investigate the mechanisms of changes in cardiac calsequestrin (CSQ2)
      trafficking on perinuclear Ca(2+) signaling, we manipulated the subcellular
      distribution of CSQ2 by overexpression of CSQ2-DsRed, which specifically
      accumulates in the perinuclear rough ER. Adult ventricular myocytes were infected
      with adenoviruses expressing CSQ2-DsRed, CSQ2-WT, or empty vector. We found that
      perinuclear enriched CSQ2-DsRed, but not normally distributed CSQ2-WT, enhanced
      nuclear Ca(2+) transients more potently than cytosolic Ca(2+) transients.
      Overexpression of CSQ2-DsRed produced more actively propagating Ca(2+) waves from
      perinuclear regions than did CSQ2-WT. Activities of the SR/ER Ca(2+)-ATPase and
      ryanodine receptor type 2, but not inositol 1,4,5-trisphosphate receptor type 2,
      were required for the generation of these perinuclear initiated Ca(2+) waves. In
      addition, CSQ2-DsRed was more potent than CSQ2-WT in inducing cellular
      hypertrophy in cultured neonatal cardiomyocytes. Our data demonstrate for the
      first time that CSQ2 retention in the rough ER/perinuclear region promotes
      perinuclear Ca(2+) signaling and predisposes to ryanodine receptor type 2
      mediated Ca(2+) waves from CSQ2-enriched perinuclear compartments and myocyte
      hypotrophy. These findings provide new insights into the mechanism of CSQ2 in
      Ca(2+) homeostasis, suggesting that rough ER-localized Ca(2+) stores can operate
      independently in raising levels of cytosolic/nucleoplasmic Ca(2+) as a source of
      Ca(2+) for Ca(2+)-dependent signaling in health and disease.

PMID- 22457351
TI  - Mammary epithelial cell polarity is regulated differentially by p73 isoforms via
      epithelial-to-mesenchymal transition.
AB  - p73 is expressed as TA and DeltaN isoforms, both of which are implicated in tumor
      suppression and/or promotion. To address how p73 possesses these opposing
      functions, we developed three-dimensional culture of MCF10A cells, which undergo
      cell morphogenesis to form polarized spheroids with hollow lumen similar to
      normal mammary acini in vivo. Here, we showed that upon knockdown of p73,
      particularly TAp73 but not DeltaNp73, MCF10A cells formed irregular and near
      normal acini without hollow lumen in three-dimensional culture. We also found
      that upon knockdown of p73 or TAp73, but not DeltaNp73, MCF10A cells underwent
      epithelial-to-mesenchymal transition (EMT) via down-regulation of E-cadherin
      coupled with up-regulation of beta-catenin and laminin V. In addition, we found
      that Snail-1, Slug, and Twist, all of which are known to act as EMT inducers by
      repressing E-cadherin expression, were increased markedly upon knockdown of p73
      and TAp73 but little if any by DeltaNp73. Furthermore, we showed that knockdown
      of p73 or TAp73 in MCF10A cells led to a marked increase in cell proliferation
      and migration. Together, our data suggest that TAp73 is necessary for maintaining
      normal cell polarity by suppressing EMT.

PMID- 22457352
TI  - Mechanisms for defining supercoiling set point of DNA gyrase orthologs: II. The
      shape of the GyrA subunit C-terminal domain (CTD) is not a sole determinant for
      controlling supercoiling efficiency.
AB  - DNA topoisomerases are essential enzymes that can overwind, underwind, and
      disentangle double-helical DNA segments to maintain the topological state of
      chromosomes. Nearly all bacteria utilize a unique type II topoisomerase, gyrase,
      which actively adds negative supercoils to chromosomes using an ATP-dependent DNA
      strand passage mechanism; however, the specific activities of these enzymes can
      vary markedly from species to species. Escherichia coli gyrase is known to favor
      supercoiling over decatenation (Zechiedrich, E. L., Khodursky, A. B., and
      Cozzarelli, N. R. (1997) Genes Dev. 11, 2580-2592), whereas the opposite has been
      reported for Mycobacterium tuberculosis gyrase (Aubry, A., Fisher, L. M.,
      Jarlier, V., and Cambau, E. (2006) Biochem. Biophys. Res. Commun. 348, 158-165).
      Here, we set out to understand the molecular basis for these differences using
      structural and biochemical approaches. Contrary to expectations based on
      phylogenetic inferences, we find that the dedicated DNA wrapping domains (the C
      terminal domains) of both gyrases are highly similar, both architecturally and in
      their ability to introduce writhe into DNA. However, the M. tuberculosis enzyme
      lacks a C-terminal control element recently uncovered in E. coli gyrase (see
      accompanying article (Tretter, E. M., and Berger, J. M. (2012) J. Biol. Chem.
      287, 18636-18644)) and turns over ATP at a much slower rate. Together, these
      findings demonstrate that C-terminal domain shape is not the sole regulatory
      determinant of gyrase activity and instead indicate that an inability to tightly
      couple DNA wrapping to ATP turnover is why M. tuberculosis gyrase cannot
      supercoil DNA to the same extent as its gamma-proteobacterial counterpart. Our
      observations demonstrate that gyrase has been modified in multiple ways
      throughout evolution to fine-tune its specific catalytic properties.

PMID- 22457353
TI  - Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A
      nonconserved acidic C-terminal tail modulates Escherichia coli gyrase activity.
AB  - DNA topoisomerases manage chromosome supercoiling and organization in all cells.
      Gyrase, a prokaryotic type IIA topoisomerase, consumes ATP to introduce negative
      supercoils through a strand passage mechanism. All type IIA topoisomerases employ
      a similar set of catalytic domains for function; however, the activity and
      specificity of gyrase are augmented by a specialized DNA binding and wrapping
      element, termed the C-terminal domain (CTD), which is appended to its GyrA
      subunit. We have discovered that a nonconserved, acidic tail at the extreme C
      terminus of the Escherichia coli GyrA CTD has a dramatic and unexpected impact on
      gyrase function. Removal of the CTD tail enables GyrA to introduce writhe into
      DNA in the absence of GyrB, an activity exhibited by other GyrA orthologs, but
      not by wild-type E. coli GyrA. Strikingly, a "tail-less" gyrase holoenzyme is
      markedly impaired for DNA supercoiling capacity, but displays normal ATPase
      function. Our findings reveal that the E. coli GyrA tail regulates DNA wrapping
      by the CTD to increase the coupling efficiency between ATP turnover and
      supercoiling, demonstrating that CTD functions can be fine-tuned to control
      gyrase activity in a highly sophisticated manner.

PMID- 22457354
TI  - Deletion of GalphaZ protein protects against diet-induced glucose intolerance via
      expansion of beta-cell mass.
AB  - Insufficient plasma insulin levels caused by deficits in both pancreatic beta
      cell function and mass contribute to the pathogenesis of type 2 diabetes. This
      loss of insulin-producing capacity is termed beta-cell decompensation. Our work
      is focused on defining the role(s) of guanine nucleotide-binding protein (G
      protein) signaling pathways in regulating beta-cell decompensation. We have
      previously demonstrated that the alpha-subunit of the heterotrimeric G(z)
      protein, Galpha(z), impairs insulin secretion by suppressing production of cAMP.
      Pancreatic islets from Galpha(z)-null mice also exhibit constitutively increased
      cAMP production and augmented glucose-stimulated insulin secretion, suggesting
      that Galpha(z) is a tonic inhibitor of adenylate cyclase, the enzyme responsible
      for the conversion of ATP to cAMP. In the present study, we show that mice
      genetically deficient for Galpha(z) are protected from developing glucose
      intolerance when fed a high fat (45 kcal%) diet. In these mice, a robust increase
      in beta-cell proliferation is correlated with significantly increased beta-cell
      mass. Further, an endogenous Galpha(z) signaling pathway, through circulating
      prostaglandin E activating the EP3 isoform of the E prostanoid receptor, appears
      to be up-regulated in insulin-resistant, glucose-intolerant mice. These results,
      along with those of our previous work, link signaling through Galpha(z) to both
      major aspects of beta-cell decompensation: insufficient beta-cell function and
      mass.

PMID- 22457356
TI  - Subunit D of RNA polymerase from Methanosarcina acetivorans contains two oxygen
      labile [4Fe-4S] clusters: implications for oxidant-dependent regulation of
      transcription.
AB  - Subunit D of multisubunit RNA polymerase from many species of archaea is
      predicted to bind one to two iron-sulfur (Fe-S) clusters, the function of which
      is unknown. A survey of encoded subunit D in the genomes of sequenced archaea
      revealed six distinct groups based on the number of complete or partial [4Fe-4S]
      cluster motifs within domain 3. Only subunit D from strictly anaerobic archaea,
      including all members of the Methanosarcinales, are predicted to bind two [4Fe
      4S] clusters. We report herein the purification and characterization of
      Methanosarcina acetivorans subunit D in complex with subunit L. Expression of
      subunit D and subunit L in Escherichia coli resulted in the purification of a D-L
      heterodimer with only partial [4Fe-4S] cluster content. Reconstitution in vitro
      with iron and sulfide revealed that the M. acetivorans D-L heterodimer is capable
      of binding two redox-active [4Fe-4S] clusters. M. acetivorans subunit D deleted
      of domain 3 (DDeltaD3) was still capable of co-purifying with subunit L but was
      devoid of [4Fe-4S] clusters. Affinity purification of subunit D or subunit
      DDeltaD3 from M. acetivorans resulted in the co-purification of endogenous
      subunit L with each tagged subunit D. Overall, these results suggest that domain
      3 of subunit D is required for [4Fe-4S] cluster binding, but the [4Fe-4S]
      clusters and domain 3 are not required for the formation of the D-L heterodimer.
      However, exposure of two [4Fe-4S] cluster-containing D-L heterodimer to oxygen
      resulted in loss of the [4Fe-4S] clusters and subsequent protein aggregation,
      indicating that the [4Fe-4S] clusters influence the stability of the D-L
      heterodimer and therefore have the potential to regulate the assembly and/or
      activity of RNA polymerase in an oxidant-dependent manner.

PMID- 22457355
TI  - Redifferentiation of expanded human pancreatic beta-cell-derived cells by
      inhibition of the NOTCH pathway.
AB  - In vitro expansion of beta-cells from adult human pancreatic islets would
      overcome donor beta-cell shortage for cell replacement therapy for diabetes.
      Using a beta-cell-specific labeling system we have shown that beta-cell expansion
      is accompanied by dedifferentiation resembling epithelial-mesenchymal transition
      and loss of insulin expression. Epigenetic analyses indicate that key beta-cell
      genes maintain open chromatin structure in expanded beta-cell-derived (BCD)
      cells, although they are not transcribed. In the developing pancreas important
      cell-fate decisions are regulated by NOTCH receptors, which signal through the
      Hairy and Enhancer of Split 1 (HES1) transcription regulator. We have reported
      that BCD cell dedifferentiation and proliferation in vitro correlate with
      reactivation of the NOTCH pathway. Inhibition of HES1 expression using shRNA
      during culture initiation results in reduced beta-cell replication and
      dedifferentiation, suggesting that HES1 inhibition may also affect BCD cell
      redifferentiation following expansion. Here, we used HES1 shRNA to down-regulate
      HES1 expression in expanded human BCD cells, showing that HES1 inhibition is
      sufficient to induce BCD cell redifferentiation, as manifested by a significant
      increase in insulin expression. Combined treatment with HES1 shRNA, cell
      aggregation in serum-free medium, and a mixture of soluble factors further
      stimulated the redifferentiation of BCD cells. In vivo analyses demonstrated the
      ability of the redifferentiated cells to replace beta-cell function in
      hyperglycemic immunodeficient mice. These findings demonstrate the
      redifferentiation potential of ex vivo expanded BCD cells and the reproducible
      differentiating effect of HES1 inhibition in these cells.

PMID- 22457357
TI  - Adaptor autoregulation promotes coordinated binding within clathrin coats.
AB  - Membrane traffic is an essential process that allows protein and lipid exchange
      between the endocytic, lysosomal, and secretory compartments. Clathrin-mediated
      traffic between the trans-Golgi network and endosomes mediates responses to the
      environment through the sorting of biosynthetic and endocytic protein cargo.
      Traffic through this pathway is initiated by the controlled assembly of a
      clathrin-adaptor protein coat on the cytosolic surface of the originating
      organelle. In this process, clathrin is recruited by different adaptor proteins
      that act as a bridge between clathrin and the transmembrane cargo proteins to be
      transported. Interactions between adaptors and clathrin and between different
      types of adaptors lead to the formation of a densely packed protein network
      within the coat. A key unresolved issue is how the highly complex adaptor
      clathrin interaction and adaptor-adaptor interaction landscape lead to the
      correct spatiotemporal assembly of the clathrin coat. Here we report the
      discovery of a new autoregulatory motif within the clathrin adaptor Gga2 that
      drives synergistic binding of Gga2 to clathrin and the adaptor Ent5. This
      autoregulation influences the temporal and/or spatial location of the Gga2-Ent5
      interaction. We propose that this synergistic binding provides built-in
      regulation to ensure the correct assembly of clathrin coats.

PMID- 22457358
TI  - alpha2beta1 integrin promotes chemoresistance against doxorubicin in cancer cells
      through extracellular signal-regulated kinase (ERK).
AB  - The role and the mechanisms by which beta1 integrins regulate the survival and
      chemoresistance of T cell acute lymphoblastic leukemia (T-ALL) still are poorly
      addressed. In this study, we demonstrate in T-ALL cell lines and primary blasts,
      that engagement of alpha2beta1 integrin with its ligand collagen I (ColI),
      reduces doxorubicin-induced apoptosis, whereas fibronectin (Fn) had no effect.
      ColI but not Fn inhibited doxorubicin-induced mitochondrial depolarization,
      cytochrome c release, and activation of caspase-9 and -3. ColI but not Fn also
      prevented doxorubicin from down-regulating the levels of the prosurvival Bcl-2
      protein family member Mcl-1. The effect of ColI on Mcl-1 occurred through the
      inhibition of doxorubicin-induced activation of c-Jun N-terminal kinase (JNK).
      Mcl-1 knockdown experiments showed that the maintenance of Mcl-1 levels is
      essential for ColI-mediated T-ALL cell survival. Furthermore, activation of
      MAPK/ERK, but not PI3K/AKT, is required for ColI-mediated inhibition of
      doxorubicin-induced JNK activation and apoptosis and for ColI-mediated
      maintenance of Mcl-1 levels. Thus, our study identifies alpha2beta1 integrin as
      an important survival pathway in drug-induced apoptosis of T-ALL cells and
      suggests that its activation can contribute to the generation of drug resistance.

PMID- 22457359
TI  - Thioredoxin-1 regulates cellular heme insertion by controlling S-nitrosation of
      glyceraldehyde-3-phosphate dehydrogenase.
AB  - NO generated by inducible NOS (iNOS) causes buildup of S-nitrosated GAPDH (SNO
      GAPDH) in cells, which then inhibits further iNOS maturation by limiting the heme
      insertion step (Chakravarti, R., Aulak, K. S., Fox, P. L., and Stuehr, D. J.
      (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 18004-18009). We investigated what
      regulates this process utilizing a slow-release NO donor (NOC-18) and studying
      changes in cellular SNO-GAPDH levels during and after NO exposure. Culturing
      macrophage-like cells with NOC-18 during cytokine activation caused buildup of
      heme-free (apo) iNOS and SNO-GAPDH. Upon NOC-18 removal, the cells quickly
      recovered their heme insertion capacity in association with rapid SNO-GAPDH
      denitrosation, implying that these processes are linked. We then altered cell
      expression of thioredoxin-1 (Trx1) or S-nitrosoglutathione reductase, both of
      which can function as a protein denitrosylase. Trx1 knockdown increased SNO-GAPDH
      levels in cells, made heme insertion hypersensitive to NO, and increased the
      recovery time, whereas Trx1 overexpression greatly diminished SNO-GAPDH buildup
      and protected heme insertion from NO inhibition. In contrast, knockdown of S
      nitrosoglutathione reductase expression had little effect on these parameters.
      Experiments utilizing C152S GAPDH confirmed that the NO effects are all linked to
      S-nitrosation of GAPDH at Cys-152. We conclude (i) that NO inhibition of heme
      insertion and its recovery can be rapid and dynamic processes and are inversely
      linked to the S-nitrosation of GAPDH and (ii) that the NO sensitivity of heme
      insertion can vary depending on the Trx1 expression level due to Trx1 acting as
      an SNO-GAPDH denitrosylase. Together, our results identify a new way that cells
      regulate heme protein maturation during inflammation.

PMID- 22457360
TI  - Endothelin induces rapid, dynamin-mediated budding of endothelial caveolae rich
      in ET-B.
AB  - Clathrin-independent trafficking pathways for internalizing G protein-coupled
      receptors (GPCRs) remain undefined. Clathrin-mediated endocytosis of receptors
      including ligand-engaged GPCRs can be very rapid and comprehensive (<10 min).
      Caveolae-mediated endocytosis of ligands and antibodies has been reported to be
      much slower in cell culture (?10 min). Little is known about the role of
      physiological ligands and specific GPCRs in regulating caveolae trafficking.
      Here, we find that one receptor for endothelin, ET-B but not ET-A, resides on
      endothelial cell surfaces in both tissue and cell culture primarily concentrated
      within caveolae. Reconstituted cell-free budding assays show that endothelins
      (ETs) induce the fission of caveolae from endothelial plasma membranes purified
      from rat lungs. Electron microcopy of lung tissue sections and tissue subcellular
      fractionation both show that endothelin administered intravascularly in rats also
      induces a significant loss of caveolae at the luminal surface of lung vascular
      endothelium. Endothelial cells in culture show that ET stimulates very rapid
      internalization of caveolae and cargo including caveolin, caveolae-targeting
      antibody, and itself. The ET-B inhibitor BQ788, but not the ET-A inhibitor BQ123,
      blocks the ET-induced budding of caveolae. Both the pharmacological inhibitor
      Dynasore and the genetic dominant negative K44A mutant of dynamin prevent this
      induced budding and internalization of caveolae. Also shRNA lentivirus knockdown
      of caveolin-1 expression prevents rapid internalization of ET and ET-B. It
      appears that endothelin can engage ET-B already highly concentrated in caveolae
      of endothelial cells to induce very rapid caveolae fission and endocytosis. This
      transport requires active dynamin function. Caveolae trafficking may occur more
      rapidly than previously documented when it is stimulated by a specific ligand to
      signaling receptors already located in caveolae before ligand engagement.

PMID- 22457362
TI  - Astellas' drug discovery strategy: focus on oncology.
AB  - Based on the goal of delivering innovative and reliable pharmaceutical products
      to cancer patients for whom no effective treatments exist, Astellas is focusing
      its efforts on a strategy of precision medicine in its drug discovery which is
      carried out at three research sites with diversity in their research platforms
      and research styles.

PMID- 22457361
TI  - Extra double-stranded RNA binding domain (dsRBD) in a squid RNA editing enzyme
      confers resistance to high salt environment.
AB  - A-to-I RNA editing is particularly common in coding regions of squid mRNAs.
      Previously, we isolated a squid editing enzyme (sqADAR2) that shows a unique
      structural feature when compared with other ADAR2 family members: an additional
      double-stranded RNA (dsRNA) binding domain (dsRBD). Alternative splicing includes
      or excludes this motif, generating a novel or a conventional variant termed
      sqADAR2a and sqADAR2b, respectively. The extra dsRBD of sqADAR2a increases its
      editing activity in vitro. We hypothesized that the high activity is due to an
      increase in the affinity of the enzyme for dsRNA. This may be important because
      protein-RNA interactions can be influenced by physical factors. We became
      particularly interested in analyzing the effects of salt on interactions between
      sqADAR2 and RNA because squid cells have a ~3-fold higher ionic strength and
      proportionally more Cl(-) than vertebrate cells. To date, in vitro biochemical
      analyses of adenosine deamination have been conducted using vertebrate-like ionic
      strength buffers containing chloride as the major anion, although the vast
      majority of cellular anions are known to be organic. We found that squid-like
      salt conditions severely impair the binding affinity of conventional ADAR2s for
      dsRNA, leading to a decrease in nonspecific and site-specific editing activity.
      Inhibition of editing was mostly due to high Cl(-) levels and not to the high
      concentrations of K(+), Na(+), and organic anions like glutamate. Interestingly,
      the extra dsRBD in sqADAR2a conferred resistance to the high Cl(-) levels found
      in squid neurons. It does so by increasing the affinity of sqADAR2 for dsRNA by
      30- or 100-fold in vertebrate-like or squid-like conditions, respectively. Site
      directed mutagenesis of squid ADAR2a showed that its increased affinity and
      editing activity are directly attributable to the RNA binding activity of the
      extra dsRBD.

PMID- 22457363
TI  - A case of stage IV neuroblastoma treated with aggressive surgery following
      intensive neoadjuvant chemotherapy with autologous stem cell transplantation.

PMID- 22457364
TI  - Trends in liver cancer mortality rates in Japan, USA, UK, France and Korea based
      on the WHO mortality database.

PMID- 22457365
TI  - Visualization of mucosal homeostasis via single- and multiphoton intravital
      fluorescence microscopy.
AB  - FIVM has provided many insights into the regulation of immunity. We report the
      validation of an approach for visualizing murine small bowel via single- and
      multiphoton FIVM. Tissue damage is limited to ~200 MUm, immediately adjacent to
      the incision, as confirmed by intravital PI staining. Treatment with 10 KDa
      dextran-FITC and 70 KDa dextran-TR confirms that perfusion is intact. Selective
      filtration of 10 KDa but not 70 KDa dextran from the blood indicated that kidney
      function is also intact. Interestingly, lamina propria vasculature is
      semipermeable to 10 KDa dextran. Next, reporter mice expressing egfp from the
      CX3CR1 locus, egfp from the FoxP3 locus, or RFP from the IL-17F locus were used
      to track DC subsets, FoxP3(+) Tregs, or Th17f cells, respectively. Resident
      cx3cr1(+/egfp) cells were sessile but actively probed the surrounding
      microenvironment. Both T cell populations patrol the lamina propria, but the
      Th17f cells migrate more rapidly than Tregs. Together, these data demonstrate
      intact vascular perfusion, while intravitally visualizing the mucosal surface of
      the small bowel. Lastly, the cx3cr1(+) DCs and T cells display activity similar
      to that found in steady-state, secondary lymphoid organs.

PMID- 22457366
TI  - HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis.
AB  - HIF-1 is active in hypoxia, such as inflamed mucosa, and HIF-1 in epithelium has
      been reported to control inflamed mucosa in IBD models. Although T cells play an
      important role for pathogenesis of IBD, the function of HIF-1 in T cells remains
      to be elucidated. We aimed to clarify the function of HIF-1 in T cells in IBD
      with focus on the balance between Treg and Teff. Double immunohistochemistry of
      colonic mucosa in IBD patients showed that HIF-1 was expressed in T cells
      infiltrating the inflamed mucosa, suggesting that HIF-1 in T cells is involved in
      the pathogenesis. DSS administration to T cell-specific HIF-1alpha KO mice showed
      more severe colonic inflammation than control mice with the up-regulation of Th1
      and Th17. Hypoxic stimulation in vitro increased Treg activation in WT T cells
      but not in HIF-1-deleted T cells. In contrast, hypoxic stimulation increased Th17
      activation, and the degree was higher in HIF-1-deleted cells than in control
      cells. These results show that hypoxia controls intestinal inflammation by
      regulating cytokine balance in a HIF-1-dependent manner, suggesting that
      strengthening HIF-1 induction in T cells at the sites of inflammation might be a
      therapeutic strategy for IBD regulation.

PMID- 22457367
TI  - CX3CL1/fractalkine is a novel regulator of normal and malignant human B cell
      function.
AB  - CX(3)CL1, or fractalkine, the unique member of the CX(3)C chemokine family,
      exists as a transmembrane glycoprotein, as well as in soluble form, each
      mediating different biological activities, and is constitutively expressed in
      many hematopoietic and nonhematopoietic tissues. CX(3)CR1, the CX(3)CL1 exclusive
      receptor, is a classical GPCR, expressed on NK cells, CD14(+) monocytes, and some
      subpopulation of T cells, B cells, and mast cells. A recent paper by our group
      has demonstrated for the first time that highly purified human B cells from
      tonsil and peripheral blood expressed CX(3)CR1 at mRNA and protein levels. In
      particular, tonsil naive, GC, and memory B cells expressed CX(3)CR1, but only GC
      centrocytes were attracted by soluble CX(3)CL1, which with its receptor, are also
      involved in the pathogenesis of several inflammatory disorders, as well as of
      cancer. Previous studies have shown that CX(3)CR1 is up-regulated in different
      types of B cell lymphoma, as well as in B-CLL. Recently, we have demonstrated
      that the CX(3)CL1/CX(3)CR1 axis is involved in the interaction of B-CLL cells
      with their microenvironment. Taken together, our data delineate a novel role for
      the CX(3)CL1/CX(3)CR1 complex in the biology of normal B cells and B-CLL cells.
      These topics are the subject of this review article.

PMID- 22457368
TI  - Neuronal nitric oxide synthase regulates endothelial inflammation.
AB  - NO, produced by the endothelium, is a modulator of vascular inflammation.
      Traditionally, eNOS was believed to be the primary source of NO in the
      endothelium. However, recent data suggest an important role for nNOS in the
      endothelium, although little is known about factors regulating this novel eNOS.
      We examined the localization, regulation, and significance of endothelial nNOS in
      this study. Primary HUVECs were used as a model system. Inflammatory changes were
      induced by stimulation with TNF. We report that unlike eNOS, nNOS is
      predominantly localized to the nucleus of resting endothelial cells. This nNOS
      also contributed to basal NO production in the resting endothelium. Ablation of
      endothelial nNOS by pharmacological inhibition (using L-NPA) or siRNA further
      enhanced cytokine-mediated inflammatory responses, such as up-regulation of VCAM
      1 and proinflammatory cytokines, as well as increased leukocyte recruitment.
      Based on these findings, we suggest a potential anti-inflammatory role of
      endothelial nNOS that can attenuate unopposed, proinflammatory cytokine actions.
      Our data indicate a novel location and an immunoregulatory role for nNOS in the
      endothelium.

PMID- 22457369
TI  - Social support and its association with health-related quality of life among
      older patients with chronic heart failure.
AB  - BACKGROUND: Social support is generally known to influence health-related quality
      of life (HRQoL), but this association is not well explored among older patients
      with chronic heart failure. AIMS: (1) To describe social support in older
      patients with chronic heart failure in relation to gender. (2) To investigate if
      age, gender, cohabitation, perceived financial situation, and disease severity
      are associated with social support. (3) To investigate if social support is
      associated with HRQoL after controlling for age, gender, and disease severity.
      METHODS: Data were collected in a sample of 349 patients (>= 65 years) with
      chronic heart failure. Patients' HRQoL was measured with the Minnesota Living
      with Heart Failure Questionnaire and the Short Form-12 Health Survey
      Questionnaire. The Interview Schedule for Social Interaction measured social
      support. Data were analysed with descriptive statistics, repeated-measure ANOVA,
      and multiple linear regression analyses with robust standard errors. RESULTS:
      Social support was generally rated high, although being a man, living alone,
      perceiving a problematic financial situation, and high disease severity (NYHA)
      were associated with lower levels of social support. Age was not associated with
      social support. Social support was generally associated with HRQoL, in particular
      the emotional dimensions. CONCLUSION: Taking social support into account when
      caring for older patients with heart failure can be of importance for improving
      or maintaining HRQoL.

PMID- 22457370
TI  - Development and evaluation of a computer-based educational program for adults
      with congenitally malformed hearts.
AB  - BACKGROUND: There is a lack of educational material for adults with congenitally
      malformed hearts. Computer-based education has shown to have significant effects
      on knowledge and management of chronic diseases. AIM: The aim of this study was
      to develop and evaluate a computer-based educational program for adults with
      congenitally malformed hearts. METHODS: The program was developed by a
      multidisciplinary team. Data were collected by questionnaires, observations, and
      structured interviews. RESULTS: The final product was a computer-based
      educational program consisting of ten separate modules, one for each particular
      malformation. The program was experienced as stimulating and easy to use. The
      appearance and quantity of the text was graded as good and the content as
      relevant and very useful. CONCLUSION: This is the first computer-based program
      developed for adults with congenitally malformed hearts. The evaluation found the
      program to have great potential as an important tool for improving care. Further
      studies are needed to test the outcomes of the program on knowledge, perceived
      control over the heart condition, anxiety/depression. and health-related quality
      of life. PRACTICE IMPLICATIONS: The program may be used as a complement to verbal
      information and every adult with a congenitally malformed hearts can receive
      individualized information from a personal CD.

PMID- 22457371
TI  - Spouses' coping alongside myocardial infarction patients.
AB  - BACKGROUND: The purpose of the research was to develop a substantive theory to
      describe the coping of myocardial infarction (MI) patients' spouses. The theory
      describes spousal coping experiences at 4 and 12 months after the patient's MI.
      METHODS: The data were collected by means of theme interviews from 28 spouses in
      the years 2006 and 2007 and analysed using Strauss and Corbin's grounded theory
      method. RESULTS: The substantive theory describes four main categories of spousal
      coping. The categories are: serene and balanced coping; action-centred coping;
      illness-centred coping; and coping based on denial of illness. CONCLUSIONS: The
      theory can be useful when developing support and counselling interventions for
      the spouses of MI patients. The study provides new knowledge about the spouses'
      coping experiences and about the factors that influence their coping over a
      longer period of time. The theory also discusses causal, contextual, and
      concurrent factors, which affect the coping experience and whose identification
      is important when seeking to support the spouses. Another application of the
      theory can be found in nursing education.

PMID- 22457372
TI  - Pre-operative education and counselling are associated with reduced anxiety
      symptoms following carotid endarterectomy: a randomized and open-label study.
AB  - BACKGROUND: Post-operative anxiety is common and may have significant impact on
      the post-operative recovery of the patients. Theatre nurse visits before surgery
      has been shown to reduce patient's anxiety levels following general surgery. AIM:
      To investigate the effect of pre-operative visits and counselling by intensive
      care unit (ICU) nurses on patient's anxiety levels following carotid
      endarterectomy. METHODS: This is an open-label and randomized clinical trial.
      Patients undergoing carotid endarterectomy were divided into study (n=60) and
      control group (n=60). For the study group, in addition to routine pre-operational
      counselling by the surgeons, ICU nurses visited the patients and provided a
      structured counselling the day before surgery. For the control group, only
      routine pre-operative counselling was provided. Anxiety levels were assessed by
      Zung self-rating anxiety scale (SAS) the day before surgery and on the day after
      being discharged from ICU to the ward. RESULTS: The two groups were comparable in
      age, sex, surgical methods, and duration of ICU stays. Following the surgery, the
      mean SAS score in the control group increased from 50.5+/-5.4 to 58.5+/-7.3
      (p=0.03), whereas the mean SAS score in the study group reduced from 51.5+/-4.3
      to 45.1+/-6.5 (p=0.02). The proportion of patients with anxiety symptoms in the
      control group was higher than in the study group following the surgery (58.3% vs.
      33.3%, p=0.001). CONCLUSIONS: Pre-operative visits and counselling by ICU nurses
      could reduce patient's anxiety levels following carotid endarterectomy.

PMID- 22457373
TI  - Increased confidence to engage in physical exertion: older ICD recipients'
      experiences of participating in an exercise training programme.
AB  - BACKGROUND: Research suggests that exercise training (ET) programmes may improve
      both physical and psychosocial functioning in implantable cardioverter
      defibrillator (ICD) recipients. Most of this research has been conducted by means
      of quantitative methods. However, knowledge of older ICD recipients' experiences
      of participating in such programmes is sparse. There is thus a need for more
      detailed qualitative data from the perspective of older patients. AIM: To
      describe older ICD recipients' experiences of participating in an ET programme.
      METHODS: A qualitative design with semistructured interviews involving 12 older
      ICD recipients who had participated in a 3-month ET programme. Mini-disc
      recordings of the interviews were transcribed verbatim and analysed using content
      analysis. RESULTS: The analysis revealed two major themes: (1) 'increased
      confidence to engage in physical exertion'; and (2) 'increased satisfaction with
      life'. The first theme is illustrated by three subthemes: 'perceived support from
      physiotherapists', 'perceiving the heart rate monitor as a motivation to
      exercise', and 'perceiving peers as motivators for enjoyment and making the
      effort to exercise'. The second theme was illustrated by the following subthemes:
      'perceived psychosocial benefits', 'perceived physical benefits', and 'exercise
      as a new health habit'. CONCLUSION: The findings indicate that exercising in a
      cardiac rehabilitation centre together with peers and supervised by skilled
      healthcare professionals may increase motivation to exert oneself, leading to
      emotional and physical benefits as well as a more social and active lifestyle for
      older ICD recipients.

PMID- 22457375
TI  - Gender differences in respiratory disturbance, sleep and daytime sleepiness in
      hypertensive patients with different degrees of obesity.
AB  - BACKGROUND: Hypertension (HT) and obesity have both been linked to obstructive
      sleep apnoea (OSA). Difficulties have been described in identifying patients with
      OSA in primary care, causing low referral rates to sleep clinics. Increased
      knowledge about gender-specific characteristics and symptoms may help to identify
      patients. AIM: The aim was to describe gender differences regarding undiagnosed
      OSA, self-rated sleep, insomnia and daytime sleepiness in middle-aged primary
      care patients with HT and different degrees of obesity. METHODS: A cross
      sectional design was used and 394 patients (52.5% women), mean age 57.8 years (SD
      6.7 years), with HT (BP >140/90 mmHg) were included. Clinical examinations,
      respiratory recordings and self-rated scales regarding OSA symptoms, sleep,
      insomnia and daytime sleepiness were used. Body mass index (BMI) was classified
      according to the criteria from the National Institutes of Health. RESULTS: Pre
      obesity and obesity classes I and II were seen among 53%, 26% and 8% of the men
      and 37%, 19% and 14% of the women, respectively. Occurrence of mild, moderate and
      severe OSA increased significantly across the BMI classes for both genders
      (p<0.01). Ninety percent of the men and 80% of the women in obesity class II had
      OSA. Insomnia was prevalent in obese patients. Other clinical variables did not
      differ between BMI classes or genders. CONCLUSION: The occurrence of
      overweight/obesity and OSA was high among both genders. A high BMI might be a
      convenient clinical marker for healthcare personnel to identify hypertensive
      patients with possible OSA in need of further evaluation and treatment.

PMID- 22457376
TI  - Documentation and interventions in the problem of caregiver burden.

PMID- 22457377
TI  - Cypriot nurses' knowledge of heart failure self-management principles.
AB  - BACKGROUND: The nurse's role as educator has become very crucial in heart failure
      management; thus, nurses must be adequately prepared to undertake this task. AIM:
      The main objective of the study was to estimate the level of Cypriot nurses'
      knowledge on basic heart failure self-care principles. METHODS: A questionnaire
      measuring knowledge on heart failure self-care principles was administered among
      cardiology nurses working in five public urban hospitals of Cyprus. Data were
      analysed by using descriptive statistics, t-test and analysis of variance for
      categorical variables (such as gender and working setting) and correlation tests
      (Pearson's) plus simple linear regression for continuous variables (such as
      working experience). RESULTS: Participants were 143 nurses. The mean heart
      failure self-care knowledge score was 13.57/20 (SD 2.33). Gender, hospital and
      cardiac clinical experience do not significantly affect scoring. Significant
      difference in the knowledge score was observed among critical care, cardiology
      and medical unit nurses (f=4.1, p=0.018). Post hoc analysis showed that this
      significant difference originated from the comparison of critical care nurses
      with cardiology unit nurses (14.1, SD 2.3 vs. 13.0, SD 2.1 respectively).
      Correlation and linear regression analyses yielded only weak negative correlation
      between correct scoring and duration of nursing practice (r=-0.262, p=0.002),
      with 6% of the total variation in scoring being explained by this relationship.
      CONCLUSIONS: Results are consistent with previous findings and it is thus under
      question whether cardiology nurses are properly educating their heart failure
      patients. Consequently, there is an urgent need for nurses to update their
      knowledge and enhance their educational skills.

PMID- 22457378
TI  - Food pattern and quality of life in metabolic syndrome patients: debatable facts.

PMID- 22457379
TI  - Psychometric properties of the Kansas City Cardiomyopathy Questionnaire (KCCQ).
AB  - BACKGROUND: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a well
      established instrument used to evaluate the health status of heart failure (HF)
      patients. There has been a lack of clarity about the best way to conceptualize
      the KCCQ. The purpose of this investigation of the KCCQ was to: (1) explore the
      factor structure with an exploratory factor analyses; (2) perform reliability and
      validity testing to determine the best factor solution for item groupings; and
      (3) determine the most meaningful components of health status captured by the
      KCCQ. METHODS AND RESULTS: A secondary analysis of data from 280 adults with
      stage-C HF enrolled from three US northeastern sites was conducted to test the
      KCCQ subscale structure. Criterion-related validity for the Self-efficacy
      subscale was tested with the Dutch Heart Failure Knowledge Scale and the Self
      care of Heart Failure Index Self-care Confidence Scale. Overall, internal
      consistency reliability (Cronbach's alpha) for the KCCQ and subscales was 0.92,
      social interference (seven items, 0.90), physical limitation (four items, 0.84),
      symptoms (eight items, 0.86), independent care (two items, 0.80), and self
      efficacy (two items, 0.63). Two items failed to correspond to a previously
      identified factor so the independent care subscale was added. Items intending to
      measure quality of life were loaded in the social interference subscale.
      CONCLUSIONS: We recommend eliminating the quality of life subscale and including
      those items in the social interference subscale, and eliminating the self
      efficacy items and re-evaluating the items related to independent care.

PMID- 22457380
TI  - STEMI--taking the acute cardiac care to the patient.

PMID- 22457381
TI  - Depression and health-related quality of life in people with coronary heart
      disease: a systematic review.
AB  - BACKGROUND: Depression affects 20% of people with coronary heart disease (CHD)
      and predicts worse health-related quality of life (HRQoL), but in primary studies
      the strength of this reported relationship has been inconsistent. AIMS AND
      METHODS: We conducted a systematic review to investigate the extent to which
      depression independently predicts subsequent physical HRQoL. We searched
      electronic databases (MEDLINE, PsycINFO, CINAHL and EMBASE) to identify
      prospective cohort studies that included CHD patients, focused on depression and
      subsequent physical HRQoL using standardised measures. Included studies were
      assessed for methodological quality. RESULTS: We identified 11 independent
      studies, of which nine showed a significant association between depression and
      subsequent physical HRQoL. There was no systematic methodological difference
      between those studies that did and did not show a significant association; in
      particular the results did not appear to be affected by the way depression or
      physical HRQoL was measured. Five of the 11 studies were of moderate to high
      methodological quality and controlled for both HRQoL and the severity of CHD at
      baseline. Four studies showed a significant association between depression and
      HRQoL. CONCLUSIONS: Depression predicts subsequent physical HRQoL and this
      association was not attributable to confounding effects of baseline HRQoL or the
      severity of the CHD. Identification of depressed CHD patients may improve
      targeting of resources at people at increased risk of worse physical HRQoL.
      Treating depression may improve subsequent physical HRQoL, though this needs to
      be established in future randomised controlled trials.

PMID- 22457382
TI  - Four countries, four views of nursing ... the best of times, the worst of times?

PMID- 22457383
TI  - Moral distress in nurses in oncology and haematology units.
AB  - One of the difficulties nurses experience in clinical practice in relation to
      ethical issues in connection with young oncology patients is moral distress. In
      this descriptive correlational study, the Moral Distress Scale-Paediatric Version
      (MDS-PV) was translated from the original language and tested on a conventional
      sample of nurses working in paediatric oncology and haematology wards, in six
      north paediatric hospitals of Italy. 13.7% of the total respondents claimed that
      they had changed unit or hospital due to moral distress. The items with the
      highest mean intensity in the sample were almost all connected with medical and
      nursing competence and have considerably higher values than frequency. The
      instrument was found to be reliable. The results confirmed the validity of the
      MDS-PV (Cronbach's alpha = 0.959). This study represents the first small-scale
      attempt to validate MDS-PV for use in paediatric oncology-haematology nurses in
      Italy.

PMID- 22457384
TI  - Stress of Conscience among psychiatric nursing staff in relation to environmental
      and individual factors.
AB  - The present study aimed at investigating the relationship between environmental
      and individual factors and Stress of Conscience among nursing staff in
      psychiatric in-patient care. A questionnaire involving six different instruments
      measuring Stress of Conscience, the ward atmosphere, the psychosocial work
      environment, Perceived Stress, Moral Sensitivity, and Mastery was answered by 93
      nursing staff at 12 psychiatric in-patient wards in Sweden. The findings showed
      that Sense of Moral Burden, Mastery, Control at Work and Angry and Aggressive
      Behavior were related to Stress of Conscience. We conclude that Mastery and
      Control at Work seemed to work as protective factors, while Sense of Moral Burden
      and perceptions of Angry and Aggressive Behavior made the nursing staff more
      vulnerable to Stress of Conscience. Future research should investigate whether
      measures to increase the level of perceived control and being part of decision
      making will decrease the level of Stress of Conscience among the staff.

PMID- 22457385
TI  - Exploring clinical wisdom in nursing education.
AB  - The recent interest in wisdom in professional health care practice is explored in
      this article. Key features of wisdom are identified via consideration of certain
      classical, ancient and modern sources. Common themes are discussed in terms of
      their contribution to 'clinical wisdom' itself and this is reviewed against the
      nature of contemporary nursing education. The distinctive features of wisdom
      (recognition of contextual factors, the place of the person and timeliness) may
      enable their significance for practice to be promoted in more coherent ways in
      nursing education. Wisdom as practical knowledge (phronesis) is offered as a
      complementary perspective within the educational preparation and practice of
      students of nursing. Certain limitations within contemporary UK nursing education
      are identified that may inhibit development of clinical wisdom. These are: the
      modularization of programmes in higher education institutions, the division of
      pastoral and academic support and the relationship between theory and practice.

PMID- 22457386
TI  - Publishing ethics in paediatric research: a cross-cultural comparative review.
AB  - The present article aims to scrutinize publishing ethics in the fields of
      paediatrics and paediatric nursing. Full-text readings of all original research
      articles in paediatrics from a high-income economy, i.e. Sweden, and from all low
      income economies in Sub-Saharan Africa, were reviewed as they were indexed and
      stored in Web of Science for the search period from 1 January 2007 to 7 October
      2009. The application of quantitative and qualitative content analysis revealed a
      marked discrepancy in publishing frequencies between the two contrasting
      economies. Authors from 16 low-income economies in Sub-Saharan Africa, with at
      least one article stored, were obviously closely linked to co-authorships and
      foreign funding sources, predominantly from Europe and the USA. Statements
      concerning conflicts of interest were frequently missing (both regions), even
      when multiple financial sources, including companies, were involved. It is
      necessary to be aware of possible systematic bias when using electronic databases
      to search for certain topics and regions. Further research regarding publishing
      ethics in paediatrics and paediatric nursing is emphasized.

PMID- 22457387
TI  - Development of an administrative ethical behaviour scale.
AB  - The aim of this study was to develop an Administrative Ethical Behaviour Scale
      (AEBS) and to determine whether nurses found their head nurses' behaviours
      ethical and to reveal head nurses' ethical and unethical administrative
      behaviour. It was conducted on 264 nurses working in five state hospitals in
      Trabzon, Turkey. Content validity index of the scale was 0.87, item-to-total
      correlations ranged from 0.50 to 0.81 and Chronbach Alpha was 0.98. The scale
      included five subscales, i.e. truthfulness and honesty, liabilities and supremacy
      of laws, rights and freedom, good human relationships and humanism, justice and
      equality. Overall, head nurses' behaviour was considered ethical by nurses;
      however, their behaviour in terms of justice and equality, good human
      relationships and humanism was not found ethical. Positions, satisfaction with
      head nurses' behaviour and frequency of contact with them affect nurses'
      opinions.

PMID- 22457388
TI  - A gamma-tocopherol-rich mixture of tocopherols maintains Nrf2 expression in
      prostate tumors of TRAMP mice via epigenetic inhibition of CpG methylation.
AB  - Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a pivotal role in
      maintaining cellular redox homeostasis and eliminating reactive toxic species.
      Nrf2 is epigenetically suppressed due to CpG hypermethylation in prostate tumors
      from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. We
      previously showed that dietary feeding of a gamma-tocopherol-rich mixture of
      tocopherols (gamma-TmT) suppressed prostate tumorigenesis in TRAMP mice
      associated with higher Nrf2 protein expression. We hypothesized that gamma-TmT
      may maintain Nrf2 through epigenetic inhibition of promoter CpG methylation. In
      this study, 8-wk-old male TRAMP mice were fed 0.1% gamma-TmT or a control diet
      for 16 wk. The methylation in the Nrf2 promoter was inhibited in the prostate of
      the gamma-TmT group compared with the control group. Protein expressions of DNA
      methyltransferase (DNMT), including DNMT1, DNMT3A, and DNMT3B, were lower in the
      prostate of the gamma-TmT group than in the controls. TRAMP-C1 cells were treated
      with 30 MUmol/L of gamma-TmT or blank medium for 5 d. The methylation in the Nrf2
      promoter was inhibited in the gamma-TmT-treated cells compared with the untreated
      cells at d 5, and mRNA and protein expressions of Nrf2 and NAD(P)H:quinone
      oxidoreductase 1 were higher. Interestingly, only DNMT3B was inhibited in the
      gamma-TmT-treated cells compared with the untreated cells. In the aggregate, our
      findings demonstrate that gamma-TmT could inhibit CpG methylation in the Nrf2
      promoter in the prostate of TRAMP mice and in TRAMP-C1 cells, which might lead to
      higher Nrf2 expression and potentially contribute to the prevention of prostate
      tumorigenesis in this TRAMP model.

PMID- 22457389
TI  - Prebiotics and the health benefits of fiber: current regulatory status, future
      research, and goals.
AB  - First defined in the mid-1990s, prebiotics, which alter the composition and
      activity of gastrointestinal (GI) microbiota to improve health and well-being,
      have generated scientific and consumer interest and regulatory debate. The Life
      Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the
      Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess
      the current state of the science and the international regulatory environment for
      prebiotics, identify research gaps, and create a strategy for future research. A
      developing body of evidence supports a role for prebiotics in reducing the risk
      and severity of GI infection and inflammation, including diarrhea, inflammatory
      bowel disease, and ulcerative colitis as well as bowel function disorders,
      including irritable bowel syndrome. Prebiotics also increase the bioavailability
      and uptake of minerals and data suggest that they reduce the risk of obesity by
      promoting satiety and weight loss. Additional research is needed to define the
      relationship between the consumption of different prebiotics and improvement of
      human health. New information derived from the characterization of the
      composition and function of different prebiotics as well as the interactions
      among and between gut microbiota and the human host would improve our
      understanding of the effects of prebiotics on health and disease and could assist
      in surmounting regulatory issues related to prebiotic use.

PMID- 22457390
TI  - Healthier home food preparation methods and youth and caregiver psychosocial
      factors are associated with lower BMI in African American youth.
AB  - Obesity disproportionately affects African American (AA) children and adolescents
      and leads to an increased risk of adult chronic diseases. Eating few meals at
      home has been implicated as a cause of obesity among youth, but to our knowledge,
      previous studies have not specifically investigated this relationship in AA
      adolescents or looked at both the healthfulness and frequency of home meals in AA
      households. The objective of the present study was to investigate the
      relationship between home food preparation and adolescent BMI in a sample of 240
      AA adolescents aged 10-15 y and their caregivers. Multiple linear regressions
      were used to model psychosocial characteristics, household factors, and
      adolescent and caregiver food preparation behaviors as predictors of adolescent
      BMI, and psychosocial and household factors as predictors of food preparation
      behavior. Adolescents in the sample had a mean BMI-for-age percentile of 70.4,
      and >90% of the sample families received at least one form of food assistance.
      Adolescent children of caregivers who used healthier cooking methods were more
      likely to use healthy cooking methods themselves (P = 0.02). Having more meals
      prepared by a caregiver was predictive of higher BMI-for-age percentile in
      adolescents (P = 0.02), but healthier cooking methods used by the caregiver was
      associated with reduced risk of adolescent overweight or obesity (P < 0.01).
      Meals prepared at home in AA households do not necessarily promote healthy BMI in
      youth. Family meals are a promising adolescent obesity prevention strategy, but
      it is important to target both frequency and healthfulness of meals prepared at
      home for effective health promotion in AA families.

PMID- 22457391
TI  - A healthy dietary pattern at midlife is associated with subsequent cognitive
      performance.
AB  - Few studies have investigated the long-term impact of overall dietary patterns
      (DP) on cognition. We evaluated the association between empirically derived DP in
      midlife and cognitive performance 13 y later. Dietary data were based on 24-h
      dietary records obtained from a subsample of the Supplementation en Vitamines et
      Mineraux Antioxydant Study. Cognitive performance was assessed via a battery of
      neuropsychological tests that included verbal fluency, the RI-48 cued recall
      test, the trail-making test, and forward and backward digit span. Three composite
      variables, for global cognitive function, verbal memory, and executive
      functioning, were built. The multivariate analyses were adjusted for baseline
      characteristics (age, gender, intervention group, education, alcohol and energy
      intake, number of dietary records, physical activity, BMI, tobacco use, self
      reported memory troubles, diabetes, hypertension, and, for women, menopausal
      status and hormone therapy use), follow-up time, history of cardiovascular
      disease, and depressive symptoms. Adjusted means +/- SEM of composite variables
      across quartiles (Q4 vs. Q1) of DP were estimated using ANCOVA. A healthy and a
      traditional DP were identified. In the multivariate model, the healthy pattern
      was associated with better global cognitive function (50.1 +/- 0.7 vs. 48.9 +/-
      0.7; P-trend = 0.001) and verbal memory (49.7 +/- 0.4 vs. 48.7 +/- 0.4; P-trend =
      0.01). These relationships were stronger in participants scoring below the gender
      specific median values for energy intake (<2490 kcal for men and <1810 for women)
      than in those scoring at or above those values. Adherence to a healthy DP in
      middle life may help preserve global cognitive function, especially verbal
      memory, when total energy intake is regulated.

PMID- 22457392
TI  - Leucine is essential for attenuating fetal growth restriction caused by a protein
      restricted diet in rats.
AB  - Certain amino acids, such as leucine (Leu) are not only substrates for protein
      synthesis but also are important regulators of protein metabolism. Moreover, it
      is known that alterations in intrauterine growth favor the development of chronic
      diseases in adulthood. Therefore, we investigated the role of Leu in combination
      with other BCAA on effects that are induced by maternal protein restriction on
      fetal growth. Wistar rats were divided into 4 groups according to the diet
      provided during pregnancy: control (C; 20% casein); V+I [5% casein + 2% L-valine
      (Val) + 2% L-isoleucine (Ile)]; KYT [5% casein + 1.8% L-lysine (Lys) + 1.2% L
      tyrosine (Tyr) + 1% L-threonine (Thr)]; and BCAA (5% casein + 1.8% L-Leu + 1.2% L
      Val + 1% L-Ile). Maternal protein restriction reduced the growth and organ weight
      of the offspring of dams receiving the V+I and KYT diets compared with the C
      group. Supplementation with BCAA reversed this growth deficit, minimizing the
      difference or restoring the mass of organs and carcass fat, the liver and muscle
      protein, and the RNA concentrations compared with newborns in the C group (P <
      0.05). These effects could be explained by the activation of the mTOR signaling
      pathway, because phosphorylation of 4E-BP1 in the liver of offspring of the BCAA
      group was greater than that in the C, V+I, and KYT groups. The present results
      identify a critical role for Leu in association with other BCAA in the activation
      of the mTOR signaling pathway for the control of altered intrauterine growth
      induced by a maternal low-protein diet.

PMID- 22457393
TI  - An index measuring adherence to complementary feeding guidelines has convergent
      validity as a measure of infant diet quality.
AB  - The complementary feeding period is an important stage of child development. The
      study aim was to develop an index reflecting the degree of adherence to
      complementary feeding guidelines, evaluate its convergent validity, and explore
      associations with socio-demographic factors and dietary pattern scores in
      childhood. Data were analyzed from the Avon Longitudinal Study of Parents and
      Children (n = 6065) using parent-completed dietary questionnaires at 6 mo of age,
      socio-demographic information, and dietary patterns derived by principal
      component analysis at age 3 y. The Complementary Feeding Utility Index (CFUI)
      consists of 14 components: breastfeeding duration, feeding to appetite, timing of
      introduction to solids, exposure to iron-rich cereals, fruit and vegetable
      intake, exposure to high-fat/-salt/-sugar foods including sugary drinks, food
      texture, and meal/snack frequency. Regression analyses were undertaken to
      investigate associations between index scores, socio-demographic factors, food
      and nutrient intakes, and dietary pattern scores at age 3 y. Milk and food intake
      at 6 mo and nutrient intake at 8 mo of age varied across quintiles of index score
      in largely the expected directions. Associations were found among index score,
      maternal age, education, social class, maternal smoking history, and prepregnancy
      BMI. After adjustment for socio-demographic factors, the index score was
      associated with "processed" [beta = -0.234 (95% CI = -0.260, -0.209)] and
      "healthy" [beta = 0.185 (95% CI = 0.155, 0.215)] dietary pattern scores at age 3
      y. The CFUI is able to discriminate across food intake, nutrient intake, and
      socio-demographic factors and is associated with later dietary patterns.

PMID- 22457394
TI  - High dietary saturated fat intake accentuates obesity risk associated with the
      fat mass and obesity-associated gene in adults.
AB  - Fat mass and obesity-associated (FTO) is the strongest genetic determinant of
      obesity identified to date. Dietary fat is a key environmental factor that may
      interact with genotype to affect risk of obesity and metabolic syndrome (MetS).
      This study investigated associations among FTO rs9939609, obesity measures, and
      MetS phenotypes in adults and determined potential modulation by dietary fat
      intake at baseline and after a 7.5-y follow-up when MetS cases and controls were
      selected. FTO rs9939609 genotype, biochemical, dietary, and lifestyle
      measurements were determined in the LIPGENE-SU.VI.MAX study (n = 1754). FTO
      rs9939609 A allele carriers had a higher risk of being overweight or obese [OR =
      1.66 (95% CI: 1.07, 2.57); P = 0.02] and of having a larger abdominal
      circumference [OR = 1.42 (95% CI: 1.01, 1.99); P = 0.04] compared with the TT
      homozygotes. These associations were independent of physical activity and energy
      intake and were maintained over the follow-up period, particularly in the MetS
      individuals. High dietary SFA intake (>= 15.5% energy) and a low dietary PUFA:SFA
      intake ratio (<0.38) further accentuated the risk of having a BMI >= 25 kg/m(2)
      and being abdominally obese. Non-risk allele carriers appeared to be unresponsive
      to dietary SFA intake or to the dietary PUFA:SFA intake ratio with respect to
      obesity measures. In conclusion, FTO rs9939609 was associated with obesity
      measures, especially in those with the MetS, which was further exacerbated by
      high dietary SFA intake at baseline and 7.5 y later. These data indicate
      important novel modulation of genetic risk by dietary fat exposure in individuals
      with increased cardiometabolic risk.

PMID- 22457395
TI  - Resistant starches protect against colonic DNA damage and alter microbiota and
      gene expression in rats fed a Western diet.
AB  - Resistant starch (RS), fed as high amylose maize starch (HAMS) or butyrylated
      HAMS (HAMSB), opposes dietary protein-induced colonocyte DNA damage in rats. In
      this study, rats were fed Western-type diets moderate in fat (19%) and protein
      (20%) containing digestible starches [low amylose maize starch (LAMS) or low
      amylose whole wheat (LAW)] or RS [HAMS, HAMSB, or a whole high amylose wheat
      (HAW) generated by RNA interference] for 11 wk (n = 10/group). A control diet
      included 7% fat, 13% protein, and LAMS. Colonocyte DNA single-strand breaks (SSB)
      were significantly higher (by 70%) in rats fed the Western diet containing LAMS
      relative to controls. Dietary HAW, HAMS, and HAMSB opposed this effect while
      raising digesta levels of SCFA and lowering ammonia and phenol levels. SSB
      correlated inversely with total large bowel SCFA, including colonic butyrate
      concentration (R(2) = 0.40; P = 0.009), and positively with colonic ammonia
      concentration (R(2) = 0.40; P = 0.014). Analysis of gut microbiota populations
      using a phylogenetic microarray revealed profiles that fell into 3 distinct
      groups: control and LAMS; HAMS and HAMSB; and LAW and HAW. The expression of
      colonic genes associated with the maintenance of genomic integrity (notably Mdm2,
      Top1, Msh3, Ung, Rere, Cebpa, Gmnn, and Parg) was altered and varied with RS
      source. HAW is as effective as HAMS and HAMSB in opposing diet-induced colonic
      DNA damage in rats, but their effects on the large bowel microbiota and
      colonocyte gene expression differ, possibly due to the presence of other fiber
      components in HAW.

PMID- 22457396
TI  - Low-cost, ready-to-use therapeutic foods can be designed using locally available
      commodities with the aid of linear programming.
AB  - According to the United Nations (UN), 25 million children <5 y of age are
      currently affected by severe acute malnutrition and need to be treated using
      special nutritional products such as ready-to-use therapeutic foods (RUTF).
      Improved formulations are in demand, but a standardized approach for RUTF design
      has not yet been described. A method relying on linear programming (LP) analysis
      was developed and piloted in the design of a RUTF prototype for the treatment of
      wasting in East African children and adults. The LP objective function and
      decision variables consisted of the lowest formulation price and the weights of
      the chosen commodities (soy, sorghum, maize, oil, and sugar), respectively. The
      LP constraints were based on current UN recommendations for the macronutrient
      content of therapeutic food and included palatability, texture, and maximum food
      ingredient weight criteria. Nonlinear constraints for nutrient ratios were
      converted to linear equations to allow their use in LP. The formulation was
      considered accurate if laboratory results confirmed an energy density difference
      <10% and a protein or lipid difference <5 g . 100 g(-1) compared to the LP
      formulation estimates. With this test prototype, the differences were 7%, and 2.3
      and -1.0 g . 100 g(-1), respectively, and the formulation accuracy was considered
      good. LP can contribute to the design of ready-to-use foods (therapeutic,
      supplementary, or complementary), targeting different forms of malnutrition,
      while using commodities that are cheaper, regionally available, and meet local
      cultural preferences. However, as with all prototype feeding products for medical
      use, composition analysis, safety, acceptability, and clinical effectiveness
      trials must be conducted to validate the formulation.

PMID- 22457397
TI  - The effects of fructose intake on serum uric acid vary among controlled dietary
      trials.
AB  - Hyperuricemia is linked to gout and features of metabolic syndrome. There is
      concern that dietary fructose may increase uric acid concentrations. To assess
      the effects of fructose on serum uric acid concentrations in people with and
      without diabetes, we conducted a systematic review and meta-analysis of
      controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library
      for relevant trials (through August 19, 2011). Analyses included all controlled
      feeding trials >= 7 d investigating the effect of fructose feeding on uric acid
      under isocaloric conditions, where fructose was isocalorically exchanged with
      other carbohydrate, or hypercaloric conditions, and where a control diet was
      supplemented with excess energy from fructose. Data were aggregated by the
      generic inverse variance method using random effects models and expressed as mean
      difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and
      quantified by I(2). A total of 21 trials in 425 participants met the eligibility
      criteria. Isocaloric exchange of fructose for other carbohydrate did not affect
      serum uric acid in diabetic and nondiabetic participants [MD = 0.56 MUmol/L (95%
      CI: -6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric
      supplementation of control diets with fructose (+35% excess energy) at extreme
      doses (213-219 g/d) significantly increased serum uric acid compared with the
      control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4,
      46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot
      be ruled out in the hypercaloric trials. These analyses do not support a uric
      acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic
      participants. Hypercaloric fructose intake may, however, increase uric acid
      concentrations. The effect of the interaction of energy and fructose remains
      unclear. Larger, well-designed trials of fructose feeding at "real world" doses
      are needed.

PMID- 22457399
TI  - Organic anion transporters and their implications in pharmacotherapy.
AB  - Organic anion transporters play an essential role in the distribution and
      excretion of numerous endogenous metabolic products and exogenous organic anions,
      including a host of widely prescribed drugs. The expression and activity of these
      transporters is influenced by several conditions, including transcriptional
      regulation, gender-dependent regulation, and genetic variation. In addition, the
      interaction of these transporters with several drugs and endogenous substrates
      has been well documented and may play a significant role in drug disposition and
      development of various disease states, such as nephrotoxicity and familial
      idiopathic hypouricemia. Members of this family of transporters have been
      localized mainly to the renal epithelia of various species. Much of the early
      research in this field has focused on their role in renal drug transport, yet
      increasing research on this family of transporters has localized them to various
      other epithelial tissues, including liver, brain, and placenta. Thus, an
      understanding of the role of these transporters in drug interaction and
      disposition in the kidney and other tissues may help in the determination of
      individual drug response, susceptibility to drug toxicity, and chemical
      carcinogenesis. This review seeks to summarize current knowledge of the molecular
      function and substrate profile of cloned organic anion transporters and to
      discuss recent progress in the understanding of the impact of interindividual
      variability, transcriptional regulation, and tissue distribution on individual
      drug response.

PMID- 22457398
TI  - Stress-induced chromatin changes: a critical view on their heritability.
AB  - The investigation of stress responses has been a focus of plant research,
      breeding and biotechnology for a long time. Insight into stress perception,
      signaling and genetic determinants of resistance has recently been complemented
      by growing evidence for substantial stress-induced changes at the chromatin
      level. These affect specific sequences or occur genome-wide and are often
      correlated with transcriptional regulation. The majority of these changes only
      occur during stress exposure, and both expression and chromatin states typically
      revert to the pre-stress state shortly thereafter. Other changes result in the
      maintenance of new chromatin states and modified gene expression for a longer
      time after stress exposure, preparing an individual for developmental decisions
      or more effective defence. Beyond this, there are claims for stress-induced
      heritable chromatin modifications that are transmitted to progeny, thereby
      improving their characteristics. These effects resemble the concept of Lamarckian
      inheritance of acquired characters and represent a challenge to the uniqueness of
      DNA sequence-based inheritance. However, with the growing insight into epigenetic
      regulation and transmission of chromatin states, it is worth investigating these
      phenomena carefully. While genetic changes (mainly transposon mobility) in
      response to stress-induced interference with chromatin are well documented and
      heritable, in our view there is no unambiguous evidence for transmission of
      exclusively chromatin-controlled stress effects to progeny. We propose a set of
      criteria that should be applied to substantiate the data for stress-induced,
      chromatin-encoded new traits. Well-controlled stress treatments, thorough
      phenotyping and application of refined genome-wide epigenetic analysis tools
      should be helpful in moving from interesting observations towards robust
      evidence.

PMID- 22457400
TI  - Occupational exposure in MRI.
AB  - This article reviews occupational exposure in clinical MRI; it specifically
      considers units of exposure, basic physical interactions, health effects,
      guideline limits, dosimetry, results of exposure surveys, calculation of induced
      fields and the status of the European Physical Agents Directive. Electromagnetic
      field exposure in MRI from the static field B(0), imaging gradients and
      radiofrequency transmission fields induces electric fields and currents in
      tissue, which are responsible for various acute sensory effects. The underlying
      theory and its application to the formulation of incident and induced field
      limits are presented. The recent International Commission on Non-Ionizing
      Radiation Protection (ICNIRP) Bundesministerium fur Arbeit und Soziales and
      Institute of Electrical and Electronics Engineers limits for incident field
      exposure are interpreted in a manner applicable to MRI. Field measurements show
      that exposure from movement within the B(0) fringe field can exceed ICNIRP
      reference levels within 0.5 m of the bore entrance. Rate of change of field dB/dt
      from the imaging gradients is unlikely to exceed the new limits, although
      incident field limits can be exceeded for radiofrequency (RF) exposure within 0.2
      0.5 m of the bore entrance. Dosimetric surveys of routine clinical practice show
      that staff are exposed to peak values of 42 +/- 24% of B(0), with time-averaged
      exposures of 5.2 +/- 2.8 mT for magnets in the range 0.6-4 T. Exposure to time
      varying fields arising from movement within the B(0) fringe resulted in peak
      dB/dt of approximately 2 T s(-1). Modelling of induced electric fields from the
      imaging gradients shows that ICNIRP-induced field limits are unlikely to be
      exceeded in most situations; however, movement through the static field may still
      present a problem. The likely application of the limits is discussed with respect
      to the reformulation of the European Union (EU) directive and its possible
      implications for MRI.

PMID- 22457402
TI  - Image quality associated with the use of an MR-compatible incubator in neonatal
      neuroimaging.
AB  - OBJECTIVES: MRI in the neonate poses significant challenges associated with
      patient transport and monitoring, and the potential for diminished image quality
      owing to patient motion. The objective of this study was to evaluate the
      usefulness of a dedicated MR-compatible incubator with integrated radiofrequency
      coils in improving image quality of MRI studies of the brain acquired in term and
      preterm neonates using standard MRI equipment. METHODS: Subjective and objective
      analyses of image quality of neonatal brain MR examinations were performed before
      and after the introduction of an MR-compatible incubator. For all studies, the
      signal-to-noise ratio (SNR) was calculated, image quality was graded (1-3) and
      each was assessed for image artefact (e.g. motion). Student's t-test and the Mann
      Whitney U-test were used to compare mean SNR values. RESULTS: 39 patients were
      included [mean gestational age 39 weeks (range 30-42 weeks); mean postnatal age
      13 days (range 1-56 days); mean weight 3.5 kg (range 1.4-4.5 kg)]. Following the
      introduction of the MR-compatible incubator, diagnostic quality scans increased
      from 50 to 89% and motion artefact decreased from 73 to 44% of studies. SNR did
      not increase initially, but, when using MR sequences and parameters specifically
      tailored for neonatal brain imaging, SNR increased from 70 to 213 (p=0.001).
      CONCLUSION: Use of an MR-compatible incubator in neonatal neuroimaging provides a
      safe environment for MRI of the neonate and also facilitates patient monitoring
      and transport. When specifically tailored MR protocols are used, this results in
      improved image quality.

PMID- 22457401
TI  - Experimental venous thrombi: MRI characteristics with histopathological
      correlation.
AB  - OBJECTIVES: The purpose of this study was to evaluate the MRI characteristics of
      venous thrombus over set time thresholds with histopathological correlation in a
      porcine model. METHODS: Inferior vena cava thrombi were induced in 12 pigs. MRI
      was performed in three pigs 2 h, 1 day, 3 days and 2 weeks after thrombus
      induction. RESULTS: The MRI characteristics were analysed in correlation with
      histopathological findings. The thrombi after 2 hours, which consisted of red
      blood cells (RBCs), showed isointensity on T(1 )weighted images (T(1)WIs) and
      hyperintensity on both T(2 )weighted images (T(2)WIs) and diffusion-weighted
      images (DWIs). The mean apparent diffusion coefficient (ADC) value was 1.93 * 10(
      3) mm(2) s(-1). The thrombi after Day 1, which consisted of RBCs and migrating
      neutrophils at the periphery, showed isointensity on T(1)WIs, slight
      hyperintensity on T(2)WIs and hypointensity on DWIs. The mean ADC value was 1.62
      * 10(-3) mm(2) s(-1) [corrected]. The thrombi after Day 3, which consisted of
      RBCs and peripheral inflammatory cells including macrophages, showed isointensity
      with peripheral hyperintense regions on T(1)WIs and hypointensity on both T(2)WIs
      and DWIs. The mean ADC value was 1.67 * 10(-3) mm(2) s(-1). After 2 weeks, the
      thrombi, which revealed RBC lysis surrounded by granulation tissues, showed
      isointensity on T(1)WIs and hyperintensity on T(2)WIs and DWIs. The mean ADC
      value was 2.48 * 10(-3) mm(2) s(-1). CONCLUSION: The temporal MRI characteristics
      seemed to be related to chemical and physical changes in RBC and organisation of
      granulation tissues. Free radicals generated by macrophages might also be related
      to some extent.

PMID- 22457403
TI  - Pleuropulmonary and abdominal paragonimiasis: CT and ultrasound findings.
AB  - OBJECTIVES: The purpose of this study was to review radiological images of
      patients with Paragonimus westermani (PW) that simultaneously involved the chest
      and abdomen. METHODS: Our study included four patients with serologically and
      histopathologically confirmed paragonimiasis. Abdomen CT (n=3) and chest CT (n=3)
      scans were available, and abdominal wall ultrasonography was performed in all
      patients. We retrospectively reviewed the clinical, radiological and
      histopathological findings of these patients. RESULTS: The most common abdominal
      CT findings were ascites and intraperitoneal or abdominal wall nodules. Low
      attenuated serpentine lesions of the liver were another common and relatively
      specific feature. CONCLUSION: Radiologists should consider the possibility of PW
      when these abdominal CT findings are noted, especially with pleural effusion or
      subpleural nodules in patients with initial abdominal symptoms.

PMID- 22457405
TI  - Laterality of motor control and breathing.

PMID- 22457404
TI  - Main clinical, therapeutic and technical factors related to patient's maximum
      skin dose in interventional cardiology procedures.
AB  - OBJECTIVE: The study aimed to characterise the factors related to the X-ray dose
      delivered to the patient's skin during interventional cardiology procedures.
      METHODS: We studied 177 coronary angiographies (CAs) and/or percutaneous
      transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the
      same radiography table. The clinical and therapeutic characteristics, and the
      technical parameters of the procedures, were collected. The dose area product
      (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber
      (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film
      (Gafchromic; International Specialty Products Advanced Materials Group, Wayne,
      NJ). Multivariate analyses were used to assess the effects of the factors of
      interest on dose. RESULTS: The mean MSD and DAP were respectively 389 mGy and 65
      Gy cm(-2) for CAs, and 916 mGy and 69 Gy cm(-2) for PTCAs. For 8% of the
      procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD
      and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model
      to PTCAs would lead to an inadequate assessment of the risk, especially for the
      highest dose values. For PTCAs, the body mass index, the therapeutic complexity,
      the fluoroscopy time and the number of cine frames were independent explanatory
      factors of the MSD, whoever the practitioner was. Moreover, the effect of
      technical factors such as collimation, cinematography settings and X-ray tube
      orientations on the DAP was shown. CONCLUSION: Optimising the technical options
      for interventional procedures and training staff on radiation protection might
      notably reduce the dose and ultimately avoid patient skin lesions.

PMID- 22457407
TI  - The association between tobacco burden and "dirty chest" is unlikely to follow a
      linear dose-response pattern.

PMID- 22457409
TI  - Acute abdominal pain and shortness of breath in a female patient.

PMID- 22457410
TI  - Pre-existing oral contrast from lanthanum carbonate: a confounding factor in CT
      mesenteric angiography.
AB  - A 69-year-old male was referred from the renal unit to radiology for
      investigation of bleeding per rectum. A CT mesenteric angiogram was performed.
      However, it was noted on the pre-contrast images that the large bowel contained
      positive oral contrast media. The procedure was abandoned as it would have been
      difficult to see extravasation of intravenous contrast from a bleeding point in
      the large bowel. The initial belief was that either the patient had been given
      oral contrast by ward staff on the assumption that it would be needed, or had had
      a recent radiological study requiring contrast, which was still present. Neither
      was the case; it emerged that the patient was taking Fosrenol (Shire
      Pharmaceuticals, Wayne, PA), a lanthanum carbonate medication used in the
      treatment of hyperphosphataemia. Lanthanum is densely radio-opaque and appears as
      positive bowel contrast on CT and plain radiography studies. When considering
      radiological studies specifically requiring the absence of oral contrast, it is
      important to be aware of the patient's drug history to avoid non-diagnostic scans
      with the associated radiation exposure.

PMID- 22457411
TI  - Radioiodine retention on percutaneous endoscopic gastrostomy tubes.
AB  - An 80-year-old male with recurrent thyroid cancer and a percutaneous endoscopic
      gastrostomy (PEG) tube in situ was referred for radioiodine therapy and was
      administered 5510 MBq I-131 sodium iodide intravenously. Sequential whole-body
      images taken over the subsequent 7 days for dosimetric evaluation revealed an
      area of persistent high uptake in the abdomen. Delayed imaging with single photon
      emission CT/CT at 15 days post administration revealed this uptake to be at the
      junction of the PEG tube with the anatomically normal stomach wall. We
      hypothesise that the PEG tube became contaminated by radioiodine secreted in the
      gastric mucosa during therapy and this radioactivity subsequently decayed with an
      increased effective half-life relative to the stomach, leading to the apparent
      hot spot.

PMID- 22457412
TI  - Primary anaplastic lymphoma kinase-negative anaplastic   large-cell lymphoma of
      the breast in a male patient.
AB  - Anaplastic large-cell lymphoma is an extremely rare lymphoma subtype. We describe
      the mammographic and ultrasonographic findings in a 51-year-old male patient who
      suffered from a palpable lump caused by this rare disease.

PMID- 22457413
TI  - Endovascular treatment of isolated systemic arterial supply to normal lung with
      coil and glue embolisation.
AB  - Surgery is the standard treatment for the extremely rare pathology of isolated
      anomalous systemic arterial supply to normal lung (ISSNL). We describe our
      experience with this anomaly in a 29-year-old male presenting with recurrent
      haemoptysis that was successfully treated with a combination of metallic coils
      and cyanoacrylate glue. In addition to contributing to the extremely limited data
      on endovascular therapeutic options in ISSNL, we also intend to raise the
      awareness among endovascular therapists of the need to be cautious ofand preserve
      the radiculomedullary/pial branches arising from an anomalous artery before
      embolising it.

PMID- 22457414
TI  - MRI findings of corticosubcortical lesions in osmotic myelinolysis: report of two
      cases.
AB  - Reports on the MRI findings of cerebral corticosubcortical lesions in osmotic
      myelinolysis (OM) are rare despite several pathological descriptions of this
      involvement. We report two patients with subcortical lesions associated with OM
      that were characteristically distributed along the crowns and sides of the
      cerebral gyri on T(2) weighted or fluid-attenuated inversion-recovery MRI. We
      also discuss the MRI characteristics of corticosubcortical lesions in OM.

PMID- 22457415
TI  - Abundant macroscopic fat in intra-abdominal lymph nodes involved in the course of
      a patient with chronic lymphocytic leukaemia: presentation of imaging findings
      with biopsy correlation.
AB  - The presence of a small amount of macroscopic fat is not unusual in the hilar
      region of normal lymph nodes. However, abundant replacement of the lymph node
      with fat is highly unusual and may appear as metastatic lymph node disease in the
      course of fat-predominant liposarcomas or in the case of coeliac disease
      complicated by cavitating lymph node syndrome. In this case report, a patient
      with chronic lymphocytic leukaemia/small lymphocytic lymphoma who demonstrated an
      increasing abundance of macroscopic fat in the diseased lymph nodes is presented.
      To the best of our knowledge, the imaging findings of abundant fat in lymph nodes
      in the course of lymphoma have not been reported before. The presence of
      macroscopic fat may be seen in the presence of actively involved lymph nodes in
      the presence of chronic lymphocytic leukaemia.

PMID- 22457416
TI  - PET/CT and MRI of intra-osseous haemangioma of the tibia.
AB  - Intra-osseous haemangioma is a rare, benign neoplasm that usually involves the
      vertebrae and craniofacial bones. Furthermore, its occurrence in the long bones
      is extremely rare. We report the findings of fluorine-18-fludeoxyglucose ((18)F
      FDG) positron emission tomography (PET)/CT and MRI in a patient with intra
      osseous haemangioma in the proximal tibia, who was initially misdiagnosed as
      having a malignancy based on (18)F-FDG PET/CT. (18)F-FDG PET/CT showed a well
      marginated osteolytic lesion with abnormal FDG uptake. The mass demonstrated low
      signal intensity on T(1) weighted MRI. On T(2) weighted images, the lesion
      appeared as a cluster of high signal intensity lobules and showed strong
      enhancement on contrast-enhanced T(1) weighted images. Surgical curettage was
      performed and histopathological examination of the excised tissue confirmed a
      cavernous haemangioma.

PMID- 22457417
TI  - Calcification in biliary hamartomatosis.
AB  - We report a case of histologically confirmed biliary hamartomatosis with
      calcifications studied by CT.

PMID- 22457418
TI  - Influence of the slow infusion of a soybean oil emulsion on plasma cytokines and
      ex vivo T cell proliferation after an esophagectomy.
AB  - BACKGROUND: Lipid emulsions have been suggested to reduce immune responses,
      particularly in severely stressed patients. The authors investigated the
      influence of the slow intravenous infusion of a soybean oil-based lipid emulsion
      on some immune parameters in patients who had undergone an esophagectomy for
      esophageal cancer. METHODS: Thirty-two patients who had undergone an
      esophagectomy were randomly divided into a lipid emulsion (LPD)-treated group and
      a control group. All patients received parenteral feeding with a glucose-based
      solution. Patients in the LPD group received 100 mL of a 20% soybean oil emulsion
      for 7 days after the esophagectomy in addition to the glucose-based feeding. A
      slow infusion rate (0.09-0.12 g/kg/h) was adopted to take account of the
      intrinsic degradation of infused lipids. Immune responses were measured based on
      lymphocyte proliferation and serum concentrations of monocyte chemoattractant
      protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF
      alpha). The authors also measured levels of rapid turnover proteins (ie,
      transferrin, prealbumin, and retinol-binding protein). RESULTS:
      Phytohemagglutinin- and concanavalin A-stimulated lymphocyte proliferation
      significantly decreased after the esophagectomy, but no significant difference
      was seen between the LPD and control groups. No significant difference in changes
      in plasma concentrations of MCP-1, IL-6 and TNF-alpha occurred between the 2
      groups either. Plasma concentrations of rapid turnover proteins did not differ
      between the groups. CONCLUSIONS: These results indicate that the lipid emulsion
      did not affect the immune parameters measured in patients who had undergone an
      esophagectomy when administered at a slow rate.

PMID- 22457419
TI  - Obesity is not associated with increased mortality and morbidity in critically
      ill children.
AB  - AIM: To evaluate the effect of obesity on mortality, length of mechanical
      ventilation, and length of stay (LOS) in critically ill children. METHODS:
      Retrospective cohort study in 2- to 18-year-olds, admitted to the pediatric
      intensive care unit (PICU) at the Children's Hospital of Wisconsin from 2005-2009
      who required invasive ventilation. Weight z score was used to categorize patients
      as normal (-1.89 to 1.04), overweight (1.05-1.65), obese (1.66-2.33), and
      severely obese (>2.33). Underweight patients were excluded. Age, gender,
      admission type, Pediatric Index of Mortality 2 score, operative status, trauma
      status, admission Pediatric Outcome Performance Category, and diagnosis
      categories were also collected. The outcomes were mortality, total ventilator
      days, and PICU LOS. Univariate analysis was used to compare the groups, and
      multivariate logistic regression was used to compare mortality. Total ventilation
      days and LOS were modeled with linear regression. RESULTS: In total, 1030
      patients were included in the study, with 753 normal weight, 137 overweight, 76
      obese, and 64 severely obese. The risk-adjusted mortality rates in overweight
      (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.62-1.82), obese (OR,
      0.68; 95% CI, 0.31-1.48), and severely obese patients (OR, 1.02; 95% CI, 0.45
      2.34) were not significantly different compared with the normal-weight group.
      Total ventilation days (P = .9628) and PICU LOS (P = .8431) were not
      significantly different between the groups after adjusting for risk factors.
      CONCLUSION: Critically ill overweight, obese, and severely obese children who
      require invasive mechanical ventilation have similar mortality, length of stay in
      the PICU, and ventilator days as compared with normal-weight children.

PMID- 22457420
TI  - Agreement on defining malnutrition.

PMID- 22457421
TI  - International consensus guidelines for nutrition therapy in pancreatitis.
AB  - Guidelines for nutrition support in pancreatitis have been inconsistently adapted
      to clinical practice. The International Consensus Guideline Committee (ICGC)
      established a pancreatitis task force to review published guidelines for
      pancreatitis in nutrition support. A PubMed search using the terms pancreatitis,
      acute pancreatitis, chronic pancreatitis, nutrition support, parenteral
      nutrition, enteral nutrition, and guidelines was conducted for the period from
      January 1999 to May 2011. Eleven guidelines were identified for review. The ICGC
      used the following process to develop unified guideline statements: summarize the
      strength of evidence (grading) of the guidelines; establish level of evidence for
      ICGC statements as high, intermediate, and low; assign published guideline levels
      of evidence; and define an ICGC grading system. International Pancreatitis
      Guideline Grades were established as follows: platinum-high level of evidence and
      consistent agreement among the guidelines; gold-acceptable level of evidence and
      no conflicting statements in guidelines; and silver-single existing guideline
      statement with no conflict in other guidelines. Eighteen ICGC statements were
      derived from the 11 published pancreatitis guidelines. Uniform agreement from
      widely disparate groups (United States, Europe, Japan, and China) resulted in 4
      platinum-level guideline statements for nutrition in pancreatitis: nutrition
      support therapy (NST) is generally not needed for mild to moderate disease, NST
      is needed for severe disease, enteral nutrition (EN) is preferred over parenteral
      nutrition (PN), and use PN when EN is contraindicated or not feasible. This
      methodology provides a template for future ICGC nutrition guideline development.

PMID- 22457422
TI  - Vitamin serum level variations between cycles of intermittent parenteral
      nutrition in adult patients with short bowel syndrome.
AB  - BACKGROUND: An alternative form of nutrition therapy for patients with short
      bowel syndrome (SBS) who do not have home parenteral nutrition (PN) available is
      the administration of the PN cycle during regular hospital admissions and oral
      vitamin supplement at home. The aim of this study was to evaluate serum levels of
      folic acid and vitamins A, B(12), C, and E before and after the PN cycle in
      patients with SBS. MATERIALS AND METHODS: This research was conducted with 10
      patients with SBS (less than 15 minutes of total barium transit time) who were
      receiving the PN cycle and oral vitamin supplement at home. Patients were
      evaluated regarding total food ingestion and oral vitamin supplement intake.
      Serum levels of vitamins were evaluated immediately after the end of each PN
      cycle (phase 1) and before the beginning of the next PN cycle (phase 2). RESULTS:
      Patients' nutrient ingestion was in accordance with recommendations for healthy
      individuals. Regarding the oral vitamin supplement intake, 20% of the patients
      presented low adherence. Although all patients had a normal serum level of folic
      acid and vitamin B(12), PN vitamin infusion during hospitalization and home oral
      vitamin supplement were not enough to make the serum levels of vitamins A, C, and
      E achieve normal values. CONCLUSION: This study documented that patients did not
      receive an adequate administration of oral vitamin supplements of vitamins A, C,
      and E through PN. More studies need to be conducted investigating higher doses of
      vitamin administration (oral or intravenous administration), assessing
      differences between water and liposoluble supplements.

PMID- 22457423
TI  - The evolving utility and emergent uses of novel lipid emulsions: new horizons and
      rediscovered prospects.

PMID- 22457424
TI  - Evolution of a complex disease resistance gene cluster in diploid Phaseolus and
      tetraploid Glycine.
AB  - We used a comparative genomics approach to investigate the evolution of a complex
      nucleotide-binding (NB)-leucine-rich repeat (LRR) gene cluster found in soybean
      (Glycine max) and common bean (Phaseolus vulgaris) that is associated with
      several disease resistance (R) genes of known function, including Rpg1b (for
      Resistance to Pseudomonas glycinea1b), an R gene effective against specific races
      of bacterial blight. Analysis of domains revealed that the amino-terminal coiled
      coil (CC) domain, central nucleotide-binding domain (NB-ARC [for APAF1,
      Resistance genes, and CED4]), and carboxyl-terminal LRR domain have undergone
      distinct evolutionary paths. Sequence exchanges within the NB-ARC domain were
      rare. In contrast, interparalogue exchanges involving the CC and LRR domains were
      common, consistent with both of these regions coevolving with pathogens. Residues
      under positive selection were overrepresented within the predicted solvent
      exposed face of the LRR domain, although several also were detected within the CC
      and NB-ARC domains. Superimposition of these latter residues onto predicted
      tertiary structures revealed that the majority are located on the surface,
      suggestive of a role in interactions with other domains or proteins. Following
      polyploidy in the Glycine lineage, NB-LRR genes have been preferentially lost
      from one of the duplicated chromosomes (homeologues found in soybean), and there
      has been partitioning of NB-LRR clades between the two homeologues. The single
      orthologous region in common bean contains approximately the same number of
      paralogues as found in the two soybean homeologues combined. We conclude that
      while polyploidization in Glycine has not driven a stable increase in family size
      for NB-LRR genes, it has generated two recombinationally isolated clusters, one
      of which appears to be in the process of decay.

PMID- 22457426
TI  - Undercontrolled temperament at age 3 predicts disordered gambling at age 32: a
      longitudinal study of a complete birth cohort.
AB  - Using data from the large, 30-year prospective Dunedin cohort study, we examined
      whether preexisting individual differences in childhood temperament predicted
      adulthood disordered gambling (a diagnosis covering the full continuum of
      gambling-related problems). A 90-min observational assessment at age 3 was used
      to categorize children into five temperament groups, including one primarily
      characterized by behavioral and emotional undercontrol. The children with
      undercontrolled temperament at 3 years of age were more than twice as likely to
      evidence disordered gambling at ages 21 and 32 than were children who were well
      adjusted at age 3. These associations could not be explained by differences in
      childhood IQ or family socioeconomic status. Cleanly demonstrating the temporal
      relation between behavioral undercontrol and adult disordered gambling is an
      important step toward building more developmentally sensitive theories of
      disordered gambling and may put researchers in a better position to begin
      considering potential routes to disordered-gambling prevention through enhancing
      self-control and emotional regulation.

PMID- 22457425
TI  - Regulation of plasmodesmatal permeability and stomatal patterning by the
      glycosyltransferase-like protein KOBITO1.
AB  - The differentiation of stomata provides a convenient model for studying pattern
      formation in plant tissues. Stomata formation is induced by a set of basic helix
      loop-helix transcription factors and inhibited by a signal transduction pathway
      initiated by TOO MANY MOUTHS (TMM) and ERECTA family (ERf) receptors. The
      formation of a proper stomata pattern is also dependent upon the restriction of
      symplastic movement of basic helix-loop-helix transcription factors into
      neighboring cells, especially in the backgrounds where the function of the
      TMM/ERf signaling pathway is compromised. Here, we describe a novel mutant of
      KOBITO1 in Arabidopsis (Arabidopsis thaliana). The kob1-3 mutation leads to the
      formation of stomata clusters in the erl1 erl2 background but not in the wild
      type. Cell-to-cell mobility assays demonstrated an increase in intercellular
      protein trafficking in kob1-3, including increased diffusion of SPEECHLESS,
      suggesting that the formation of stomata clusters is due to an escape of cell
      fate-specifying factors from stomatal lineage cells. While plasmodesmatal
      permeability is increased in kob1-3, we did not detect drastic changes in callose
      accumulation at the neck regions of the plasmodesmata. Previously, KOBITO1 has
      been proposed to function in cellulose biosynthesis. Our data demonstrate that
      disruption of cellulose biosynthesis in the erl1 erl2 background does not lead to
      the formation of stomata clusters, indicating that cellulose biosynthesis is not
      a major determining factor for regulating plasmodesmatal permeability. Analysis
      of KOBITO1 structure suggests that it is a glycosyltransferase-like protein.
      KOBITO1 might be involved in a carbohydrate metabolic pathway that is essential
      for both cellulose biosynthesis and the regulation of plasmodesmatal
      permeability.

PMID- 22457427
TI  - The neurogenetics of nice: receptor genes for oxytocin and vasopressin interact
      with threat to predict prosocial behavior.
AB  - Oxytocin, vasopressin, and their receptor genes influence prosocial behavior in
      the laboratory and in the context of close relationships. These peptides may also
      promote social engagement following threat. However, the scope of their prosocial
      effects is unknown. We examined oxytocin receptor (OXTR) polymorphism rs53576, as
      well as vasopressin receptor 1a (AVPR1a) polymorphisms rs1 and rs3 in a national
      sample of U.S. residents (n = 348). These polymorphisms interacted with perceived
      threat to predict engagement in volunteer work or charitable activities and
      commitment to civic duty. Specifically, greater perceived threat predicted
      engagement in fewer charitable activities for individuals with A/A and A/G
      genotypes of OXTR rs53576, but not for G/G individuals. Similarly, greater
      perceived threat predicted lower commitment to civic duty for individuals with
      one or two short alleles for AVPR1a rs1, but not for individuals with only long
      alleles. Oxytocin, vasopressin, and their receptor genes may significantly
      influence prosocial behavior and may lie at the core of the caregiving behavioral
      system.

PMID- 22457428
TI  - An unusual cause of syncope.

PMID- 22457429
TI  - The hormonal profile of norethindrone acetate: rationale for add-back therapy
      with gonadotropin-releasing hormone agonists in women with endometriosis.
AB  - Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of
      endometriosis-associated pelvic pain. The use of hormonal add-back therapy can
      alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while
      preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique
      progestin that has both estrogenic and androgenic properties and is effective as
      an add-back regimen without estrogen supplementation. Through its estrogenic
      activity, NETA exerts beneficial effects on bone mineral density and vasomotor
      symptoms in women treated with GnRHa. In addition, NETA exhibits strong
      endometrial antiproliferative effects, which may result in further benefits for
      the endometriosis patient population. However, NETA add-back may be associated
      with progestogenic side effects and may lower high-density lipoprotein due to
      androgenic activity. These effects must be balanced with the overall benefits of
      NETA add-back therapy.

PMID- 22457430
TI  - Noninvasive prediction of intra-amniotic infection and/or inflammation in preterm
      premature rupture of membranes.
AB  - OBJECTIVE: To develop a model based on noninvasive parameters to predict the
      probability of intra-amniotic infection and/or inflammation (IAI) in women with
      preterm premature rupture of membranes (PPROMs). METHODS: Maternal blood was
      collected for determination of the C-reactive protein (CRP) level and white blood
      cell (WBC) count immediately after amniocentesis in 171 consecutive women with
      PPROMs. Intra-amniotic infection and/or inflammation was defined as a positive
      amniotic fluid (AF) culture and/or an elevated AF interleukin 6 level (>=2.6
      ng/mL). RESULTS: A risk score based on a model including maternal blood CRP, WBC,
      parity, and gestational age was calculated for each patient. The model was shown
      to have an adequate goodness of fit (P = .516), and the area under the receiver
      operating characteristic curve was 0.848, indicating very good discrimination.
      CONCLUSION: The noninvasive model based on maternal blood CRP, WBC, parity, and
      gestational age is highly predictive of IAI in women with PPROMs.

PMID- 22457431
TI  - Binder of sperm 1 and epididymal sperm binding protein 1 are associated with
      different bull sperm subpopulations.
AB  - Previously, we showed that binder of sperm 1 (BSP1) and epididymal sperm binding
      protein 1 (ELSPBP1) proteins are more abundant in the immotile bovine sperm
      subpopulation following cryopreservation. In this study, we investigated the
      association of BSP1 and ELSPBP1 with sperm in relation to their ability to
      survive the cryopreservation process. Fresh and cryopreserved semen samples from
      the same ejaculate collected from nine Holstein bulls were incubated with a
      fixable viability probe, fixed and permeabilised and then immunolabelled with
      rabbit anti-BSP1, rabbit anti-ELSPBP1 or rabbit IgG as negative control.
      Spermatozoa were then incubated with Alexa 488-conjugated secondary antibody and
      Hoechst 33342. For each sample, 10 000 'Hoechst positive' events were analysed by
      flow cytometry. Alternatively, sperm populations were obtained by fluorescence
      activated cell sorting. In freshly ejaculated live sperm, two distinct BSP1
      detection patterns were revealed: a first population where BSP1 is present along
      the flagellar region (P1 subpopulation) and a second population where BSP1 is
      localised on both the flagellar and the acrosomal regions (P3 subpopulation). The
      dead population presented a BSP1 distribution similar to P3 but with a more
      intense fluorescence signal (P4 subpopulation). In the corresponding
      cryopreserved samples, all sperm in the P3 subpopulation were dead while only a
      small proportion of the P1 subpopulation was dead (P2 subpopulation). ELSPBP1 was
      detected only in dead spermatozoa and in comparable proportions in both freshly
      ejaculated and cryopreserved semen. These results show that the presence of BSP1
      over the acrosomal region characterises spermatozoa sensitive to cryopreservation
      and that ELSPBP1 characterises spermatozoa that are already dead at ejaculation.

PMID- 22457432
TI  - Luteal maintenance of pregnancy in the African elephant (Loxodonta africana).
AB  - The ovaries of eight African elephant foetuses and their mothers between 2 and 22
      months of gestation, and those of two cycling and two lactating elephants, were
      examined grossly, histologically and immunocytochemically, with emphasis on the
      development and regression of accessory corpora lutea (CL) of pregnancy and the
      steroidogenic capacities of the accessory CL and the foetal ovaries. The results
      supported recent findings that the accessory CL form as a result of
      luteinisation, with and without ovulation, of medium-sized follicles during the 3
      week inter-luteal period of the oestrous cycle. They enlarge significantly and
      become steroidogenically active around 5 weeks of gestation, probably in response
      to the placental lactogen which is secreted by the implanting trophoblast of the
      conceptus. The large luteal cells stained strongly for 3beta hydroxysteroid
      dehydrogenase (3betaHSD) activity throughout the 22-month gestation period
      although they showed vacuolation and other degenerative changes in the final
      months of gestation coincident with hypertrophy and hyperplasia of 3betaHSD
      positive interstitial cells in the foetal gonads. It is proposed that the
      progestagens secreted by the enlarged gonads of the elephant foetus may function
      both to assist the maternal ovaries in supporting the pregnancy state and to
      induce torpor and intrauterine immobility of the rapidly growing foetus.

PMID- 22457433
TI  - Impact of the LH surge on granulosa cell transcript levels as markers of oocyte
      developmental competence in cattle.
AB  - In the case of in vitro embryonic production, it is known that not all oocytes
      detain the developmental capacity to form an embryo. This capacity appears to be
      acquired through completion of folliculogenesis, during which the oocyte and
      follicular cells influence their respective destinies. The differentiation status
      of granulosa cells (GCs) could therefore offer an indicator of oocyte quality.
      The aim of this study was to compare mRNA transcript abundance in GCs associated
      with oocytes that subsequently reach or not the blastocyst stage. GCs were
      collected from cattle following an ovarian stimulation protocol that did or did
      not include the administration of LH. GCs were classified according to the
      developmental stage achieved by the associated oocytes. Transcript abundance was
      measured by microarray. Follicles (n=189) obtained from cows before and after the
      LH surge were essentially similar and the rates of oocytes reaching the
      blastocyst stage were not significantly different (52 vs 41%), but blastocyst
      quality was significantly better in the post-LH-surge group. In GCs from the pre
      LH-surge group and associated with developmentally competent oocytes, 18
      overexpressed and 22 underexpressed transcripts were found, including novel
      uncharacterized transcripts, whereas no differentially expressed transcripts were
      associated with developmentally different oocytes in the post-LH-surge group. The
      novel transcriptomic response associated with LH appeared to mask the difference.
      Based on oocyte developmental competence, the period prior to the LH surge
      appears best suited for studying competence-associated mRNA transcripts in bovine
      follicle cells.

PMID- 22457434
TI  - The effect of oviductal deleted in malignant brain tumor 1 over porcine sperm is
      mediated by a signal transduction pathway that involves pro-AKAP4
      phosphorylation.
AB  - The interaction between sperm and oviduct results in the selection of sperm with
      certain qualities. Porcine oviductal deleted in malignant brain tumor 1, DMBT1
      (previously called sperm-binding glycoprotein, SBG), has been proposed to be
      implicated in sperm selection through acrosome alteration and suppression of
      motility of a subpopulation of sperm that have begun capacitation prematurely. It
      produces in vitro acrosome alteration and decrease of motility of boar sperm,
      concomitant with tyrosine phosphorylation of a 97 kDa sperm protein (p97). We
      hypothesized that the phosphorylation of p97 may be a link between DMBT1 sensing
      by a subpopulation of boar sperm and its biological effect. In this work, p97 was
      identified by mass spectrometry and immunoprecipitation as a porcine homologue of
      AKAP4. Pro-AKAP4 was localized by immunofluorescence and subcellular
      fractionation to the periacrosomal membranes and was shown to be tyrosine
      phosphorylated by DMBT1 regardless of the presence of calcium or bicarbonate, and
      of cAMP analogs, protein kinase A inhibitors, or a protein kinase C inductor. A
      processed ~80 kDa form of AKAP4 was also detected at the tail of boar sperm,
      which was not tyrosine phosphorylated by DMBT1 under the conditions tested.
      Immunohistochemistry of testis showed presence of AKAP4 in boar sperm precursor
      cells. The evidence presented here supports the involvement of AKAP4 in the
      formation of the fibrous sheath on boar precursor sperm cells and implicates the
      phosphorylation of pro-AKAP4 as an early step in the signal transduction pathway
      gated by DMBT1 that leads to sperm selection through acrosome alteration.

PMID- 22457435
TI  - FGF10 inhibits dominant follicle growth and estradiol secretion in vivo in
      cattle.
AB  - Fibroblast growth factors (FGFs) are involved in paracrine control of follicle
      development. It was previously demonstrated that FGF10 decreases estradiol (E(2))
      secretion in granulosa cell culture and that theca cell FGF10 mRNA expression is
      decreased in healthy follicles from abattoir ovaries. The main objectives of this
      study were to evaluate FGF10 and FGFR2b mRNA expression during follicular
      development in vivo, to evaluate the effect of FGF10 on follicle growth using Bos
      taurus taurus cows as a model, and to gain more insight into the mechanisms
      through which FGF10 inhibits steroidogenesis. Messenger RNA encoding both FGF10
      and FGFR2b (main FGF10 receptor) was significantly more expressed in subordinate
      follicles (SFs) than in dominant follicles (DFs). The intrafollicular injection
      of FGF10 into the largest growing follicle at 7-8 mm in diameter interrupted the
      DF growth in a dose-dependent manner (11+/-0.4, 8.3+/-1 and 5.9+/-0.3 mm for 0,
      0.1, and 1 MUg/ml FGF10, respectively, at 72 h after treatment; P<0.05). In a
      third experiment, follicles were obtained 24 h after FGF10 (1 MUg/ml) or PBS
      treatment through ovariectomy. In theca cells, FGF10 treatment did not affect
      mRNA encoding steroidogenic enzymes, LHCGR and IGFBPs, but significantly
      upregulated FGF10 mRNA expression. The expression of CYP19A1 mRNA in granulosa
      cells was downregulated by FGF10 treatment, which was accompanied by a 50-fold
      decrease in E(2) production, and decreased cyclin D2 mRNA. These results have
      shown that FGF10 and its receptor FGFR2b are more expressed in SFs and provide
      solid in vivo evidence that FGF10 acts as an important regulator of follicular
      growth in cattle.

PMID- 22457436
TI  - Comment on: periarticular osteoporosis: a useful feature in the diagnosis of
      early rheumatoid arthritis? Reliability and validity in a cross-sectional
      diagnostic study using dual-energy X-ray absorptiometry.

PMID- 22457437
TI  - Evaluation of Chronic Kidney Disease Epidemiology Collaboration equation to
      estimate glomerular filtration rate in scleroderma patients.
AB  - OBJECTIVE: Renal involvement in SSc is often subclinical and chronic kidney
      disease (CKD) develops, with slow worsening of glomerular filtration rate (GFR).
      The present investigation was undertaken in order to study how well the Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) correlates with measured GFR
      (mGFR) in a group of SSc patients with serum creatinine (sCr) in the normal
      range. METHODS: Forty-one scleroderma patients (37 females and 4 males) with a
      median age of 46 years were enrolled. GFR was measured using technetium-99 m DTPA
      (Tc-99 m DTPA). The modified Cockroft-Gault formula, 4- and 7-variable
      Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations were used for
      estimated GFR (eGFR). RESULTS: mGFR showed a median value of 84 ml/min (range
      32.8-121.2 ml/min). Seven patients had reduced GFR (<60 ml/min), 19 had GFR
      within 60-90 ml/min and 15 had GFR >90 ml/min. The results showed mild
      correlation between the BSA-modified Cockroft-Gault and mGFR (P > 0.05), mild
      statistically significant correlation with 4-variable MDRD (P < 0.05), high
      statistically significant correlation with 7-variable MDRD (P = 0.01), but the
      greatest correlation was obtained using CKD-EPI (P = 0.002). No correlation with
      age, disease duration or subset of disease was found. CONCLUSIONS: In scleroderma
      patients with normal sCr value, CKD-EPI is a useful formula to assess GFR.

PMID- 22457438
TI  - Assessment and management of vulval pain.

PMID- 22457439
TI  - Influenza vaccination in healthcare professionals.

PMID- 22457440
TI  - Universal health coverage for India.

PMID- 22457441
TI  - A scaly rash on the hands.

PMID- 22457443
TI  - BMJ readers raise almost 34,000 pound for Lifebox.

PMID- 22457444
TI  - Times like these you need some "One Four Five".

PMID- 22457445
TI  - Bad medicine: modern medicine.

PMID- 22457446
TI  - Our relationship with poo.

PMID- 22457447
TI  - 5m Pound UK study aims to discover what causes cleft lip and palate.

PMID- 22457448
TI  - NHS should replace PIP implants even when privately fitted.

PMID- 22457449
TI  - Routine testicular self examination: it's time to stop.

PMID- 22457450
TI  - What companies don't tell you about screening.

PMID- 22457451
TI  - A trail of artificial vestibular stimulation: electricity, heat, and magnet.
AB  - The interaction between the magnetic field of a magnetic resonance imaging (MRI)
      machine and ion currents within the inner-ear endolymph results in a Lorentz
      force. This force produces a pressure that pushes on the cupula within the
      semicircular canals causing nystagmus and vertigo. Here I discuss several
      implications of this unique and noninvasive way to stimulate the vestibular
      system in experimental neurophysiology and clinical neurology.

PMID- 22457452
TI  - Glucose is an adequate energy substrate for the depolarizing action of GABA and
      glycine in the neonatal rat spinal cord in vitro.
AB  - In vitro studies have repeatedly demonstrated that the neurotransmitters gamma
      aminobutyric acid (GABA) and glycine depolarize immature neurons in many areas of
      the CNS, including the spinal cord. This widely accepted phenomenon was recently
      challenged by experiments showing that the depolarizing action of GABA on
      neonatal hippocampus and neocortex in vitro was prevented by adding energy
      substrates (ES), such as the ketone body metabolite dl-beta-hydroxybutyric acid
      (DL-BHB), lactate, or pyruvate to the artificial cerebrospinal fluid (ACSF). It
      was suggested that GABA-induced depolarizations in vitro might be an artifact due
      to inadequate energy supply when glucose is the sole energy source, consistent
      with the energy metabolism of neonatal rat brain being largely dependent on ESs
      other than glucose. Here we examined the effects of these ESs (DL-BHB, lactate,
      pyruvate) on inhibitory postsynaptic potentials (IPSPs) recorded from neonatal
      rat lumbar spinal cord motoneurons (MNs), in vitro. We report that supplementing
      the ACSF with physiologic concentrations of DL-BHB, lactate, or pyruvate does not
      alter the reversal potential of IPSPs (E(IPSP)). Only high concentrations of
      pyruvate hyperpolarized E(IPSP). In addition, the depolarizing action of GABA on
      primary afferent terminals was not affected by supplementing the ACSF with ES at
      physiologic concentrations. We conclude that depolarizing IPSPs in immature MNs
      and the primary afferent depolarizations are not caused by inadequate energy
      supply. Glucose at its standard concentration appears to be an adequate ES for
      the neonatal spinal cord in vitro.

PMID- 22457453
TI  - Greater benefits of multisensory integration during complex sensorimotor
      transformations.
AB  - Multisensory integration enables rapid and accurate behavior. To orient in space,
      sensory information registered initially in different reference frames has to be
      integrated with the current postural information to produce an appropriate motor
      response. In some postures, multisensory integration requires convergence of
      sensory evidence across hemispheres, which would presumably lessen or hinder
      integration. Here, we examined orienting gaze shifts in humans to visual,
      tactile, or visuotactile stimuli when the hands were either in a default
      uncrossed posture or a crossed posture requiring convergence across hemispheres.
      Surprisingly, we observed the greatest benefits of multisensory integration in
      the crossed posture, as indexed by reaction time (RT) decreases. Moreover, such
      shortening of RTs to multisensory stimuli did not come at the cost of increased
      error propensity. To explain these results, we propose that two accepted
      principles of multisensory integration, the spatial principle and inverse
      effectiveness, dynamically interact to aid the rapid and accurate resolution of
      complex sensorimotor transformations. First, early mutual inhibition of initial
      visual and tactile responses registered in different hemispheres reduces error
      propensity. Second, inverse effectiveness in the integration of the weakened
      visual response with the remapped tactile representation expedites the generation
      of the correct motor response. Our results imply that the concept of inverse
      effectiveness, which is usually associated with external stimulus properties,
      might extend to internal spatial representations that are more complex given
      certain body postures.

PMID- 22457455
TI  - Increase in flexor but not extensor corticospinal motor outputs following
      ischemic nerve block.
AB  - Human motor cortex is capable of rapid and long-lasting reorganization, evident
      globally, as shifts in body part representations, and at the level of individual
      muscles as changes in corticospinal excitability. Representational shifts provide
      an overview of how various body parts reorganize relative to each other but do
      not tell us whether all muscles in a given body part reorganize in the same
      manner and to the same extent. Transcranial magnetic stimulation (TMS) provides
      information about individual muscles and can therefore inform us about the
      uniformity of plastic changes within a body part. We used TMS to investigate
      changes in corticospinal excitability of forearm flexors and extensors after
      inflation of a tourniquet around the wrist. Motor evoked potential (MEP)
      amplitudes and input/output (I/O) curves were obtained from wrist flexors and
      extensors simultaneously before and during block. TMS was delivered to the
      optimal site for eliciting MEPs in flexors in experiment 1, extensors in
      experiment 2, and both flexors and extensors in experiment 3. In all experiments
      flexor MEP amplitude increased during block while extensor MEP amplitude showed
      no systematic change, and the slope of flexor but not extensor I/O curves
      increased. Flexor H-reflex amplitude normalized to maximal M wave showed
      negligible changes during block, suggesting that the increase in corticospinal
      excitability in the flexors cannot be completely explained by increased
      excitability at the spinal cord level. These findings show that forearm flexors
      and extensors differ in their potential for plastic changes, highlight the
      importance of investigating how experimentally induced plasticity affects
      anatomically close, but functionally distinct, muscle groups, and suggest that
      rehabilitation interventions aiming to alter cortical organization should
      consider the differential sensitivity of various muscle groups to plasticity
      processes.

PMID- 22457454
TI  - Inferring the role of inhibition in auditory processing of complex natural
      stimuli.
AB  - Intracellular studies have revealed the importance of cotuned excitatory and
      inhibitory inputs to neurons in auditory cortex, but typical spectrotemporal
      receptive field models of neuronal processing cannot account for this overlapping
      tuning. Here, we apply a new nonlinear modeling framework to extracellular data
      recorded from primary auditory cortex (A1) that enables us to explore how the
      interplay of excitation and inhibition contributes to the processing of complex
      natural sounds. The resulting description produces more accurate predictions of
      observed spike trains than the linear spectrotemporal model, and the properties
      of excitation and inhibition inferred by the model are furthermore consistent
      with previous intracellular observations. It can also describe several nonlinear
      properties of A1 that are not captured by linear models, including intensity
      tuning and selectivity to sound onsets and offsets. These results thus offer a
      broader picture of the computational role of excitation and inhibition in A1 and
      support the hypothesis that their interactions play an important role in the
      processing of natural auditory stimuli.

PMID- 22457456
TI  - Dual pools of actin at presynaptic terminals.
AB  - We investigated actin's function in vesicle recycling and exocytosis at lamprey
      synapses and show that FM1-43 puncta and phalloidin-labeled filamentous actin (F
      actin) structures are colocalized, yet recycling vesicles are not contained
      within F-actin clusters. Additionally, phalloidin also labels a plasma membrane
      associated cortical actin. Injection of fluorescent G-actin revealed activity
      independent dynamic actin incorporation into presynaptic synaptic vesicle
      clusters but not into cortical actin. Latrunculin-A, which sequesters G-actin,
      dispersed vesicle-associated actin structures and prevented subsequent labeled G
      actin and phalloidin accumulation at presynaptic puncta, yet cortical phalloidin
      labeling persisted. Dispersal of presynaptic F-actin structures by latrunculin-A
      did not disrupt vesicle clustering or recycling or alter the amplitude or
      kinetics of excitatory postsynaptic currents (EPSCs). However, it slightly
      enhanced release during repetitive stimulation. While dispersal of presynaptic
      actin puncta with latrunculin-A failed to disperse synaptic vesicles or inhibit
      synaptic transmission, presynaptic phalloidin injection blocked exocytosis and
      reduced endocytosis measured by action potential-evoked FM1-43 staining.
      Furthermore, phalloidin stabilization of only cortical actin following
      pretreatment with latrunculin-A was sufficient to inhibit synaptic transmission.
      Conversely, treatment of axons with jasplakinolide, which induces F-actin
      accumulation but disrupts F-actin structures in vivo, resulted in increased
      synaptic transmission accompanied by a loss of phalloidin labeling of cortical
      actin but no loss of actin labeling within vesicle clusters. Marked synaptic
      deficits seen with phalloidin stabilization of cortical F-actin, in contrast to
      the minimal effects of disruption of a synaptic vesicle-associated F-actin, led
      us to conclude that two structurally and functionally distinct pools of actin
      exist at presynaptic sites.

PMID- 22457457
TI  - Integration of target and hand position signals in the posterior parietal cortex:
      effects of workspace and hand vision.
AB  - Previous findings suggest the posterior parietal cortex (PPC) contributes to arm
      movement planning by transforming target and limb position signals into a desired
      reach vector. However, the neural mechanisms underlying this transformation
      remain unclear. In the present study we examined the responses of 109 PPC neurons
      as movements were planned and executed to visual targets presented over a large
      portion of the reaching workspace. In contrast to previous studies, movements
      were made without concurrent visual and somatic cues about the starting position
      of the hand. For comparison, a subset of neurons was also examined with
      concurrent visual and somatic hand position cues. We found that single cells
      integrated target and limb position information in a very consistent manner
      across the reaching workspace. Approximately two-thirds of the neurons with
      significantly tuned activity (42/61 and 30/46 for left and right workspaces,
      respectively) coded targets and initial hand positions separably, indicating no
      hand-centered encoding, whereas the remaining one-third coded targets and hand
      positions inseparably, in a manner more consistent with the influence of hand
      centered coordinates. The responses of both types of neurons were largely
      invariant with respect to the presence or absence of visual hand position cues,
      suggesting their corresponding coordinate frames and gain effects were unaffected
      by cue integration. The results suggest that the PPC uses a consistent scheme for
      computing reach vectors in different parts of the workspace that is robust to
      changes in the availability of somatic and visual cues about hand position.

PMID- 22457458
TI  - Effector selection precedes reach planning in the dorsal parietofrontal cortex.
AB  - Experimental evidence and computational modeling suggest that target selection
      for reaching is associated with the parallel encoding of multiple movement plans
      in the dorsomedial posterior parietal cortex (dmPPC) and the caudal part of the
      dorsal premotor cortex (PMdc). We tested the hypothesis that a similar mechanism
      also accounts for arm selection for unimanual reaching, with simultaneous and
      separate motor goal representations for the left and right arms existing in the
      right and left parietofrontal cortex, respectively. We recorded simultaneous
      electroencephalograms and functional MRI and studied a condition in which
      subjects had to select the appropriate arm for reaching based on the color of an
      appearing visuospatial target, contrasting it to a condition in which they had
      full knowledge of the arm to be used before target onset. We showed that
      irrespective of whether subjects had to select the arm or not, activity in dmPPC
      and PMdc was only observed contralateral to the reaching arm after target onset.
      Furthermore, the latency of activation in these regions was significantly delayed
      when arm selection had to be achieved during movement planning. Together, these
      results demonstrate that effector selection is not achieved through the
      simultaneous specification of motor goals tied to the two arms in bilateral
      parietofrontal cortex, but suggest that a motor goal is formed in these regions
      only after an arm is selected for action.

PMID- 22457459
TI  - Sustained BOLD and theta activity in auditory cortex are related to slow stimulus
      fluctuations rather than to pitch.
AB  - Human functional MRI (fMRI) and magnetoencephalography (MEG) studies indicate a
      pitch-specific area in lateral Heschl's gyrus. Single-cell recordings in monkey
      suggest that sustained-firing, pitch-specific neurons are located lateral to
      primary auditory cortex. We reevaluated whether pitch strength contrasts reveal
      sustained pitch-specific responses in human auditory cortex. Sustained BOLD
      activity in auditory cortex was found for iterated rippled noise (vs. noise or
      silence) but not for regular click trains (vs. jittered click trains or silence).
      In contrast, iterated rippled noise and click trains produced similar pitch
      responses in MEG. Subsequently performed time-frequency analysis of the MEG data
      suggested that the dissociation of cortical BOLD activity between iterated
      rippled noise and click trains is related to theta band activity. It appears that
      both sustained BOLD and theta activity are associated with slow non-pitch
      specific stimulus fluctuations. BOLD activity in the inferior colliculus was
      sustained for both stimulus types and varied neither with pitch strength nor with
      the presence of slow stimulus fluctuations. These results suggest that BOLD
      activity in auditory cortex is much more sensitive to slow stimulus fluctuations
      than to constant pitch, compromising the accessibility of the latter. In
      contrast, pitch-related activity in MEG can easily be separated from theta band
      activity related to slow stimulus fluctuations.

PMID- 22457460
TI  - Human brain cortical correlates of short-latency afferent inhibition: a combined
      EEG-TMS study.
AB  - When linking in time electrical stimulation of the peripheral nerve with
      transcranial magnetic stimulation (TMS), the excitability of the motor cortex can
      be modulated to evoke clear inhibition, as reflected by the amplitude decrement
      in the motor-evoked potentials (MEPs). This specific property, designated short
      latency afferent inhibition (SAI), occurs when the nerve-TMS interstimulus
      interval (ISI) is approximately 25 ms and is considered to be a corticothalamic
      phenomenon. The aim of the present study was to use the electroencephalographic
      (EEG) responses to navigated-TMS coregistration to better characterize the
      neuronal circuits underlying SAI. The present experimental set included magnetic
      resonance imaging (MRI)-navigated TMS and 60-channel TMS-compatible EEG devices.
      TMS-evoked EEG responses and MEPs were analyzed in eight healthy volunteers; ISIs
      between median nerve and cortical stimulation were determined relative to the
      latency of the individual N20 component of the somatosensory-evoked potential
      (SEP) obtained after stimulation of the median nerve. ISIs from the latency of
      the N20 plus 3 ms and N20 plus 10 ms were investigated. In all experimental
      conditions, TMS-evoked EEG responses were characterized by a sequence of negative
      deflections peaking at approximately 7, 44, and 100 ms alternating with positive
      peaks at approximately 30, 60, and 180 ms post-TMS. Moreover, ISI N20+3 ms
      modulated both EEG-evoked activity and MEPs. In particular, it inhibited MEP
      amplitudes, attenuated cortical P60 and N100 responses, and induced motor cortex
      beta rhythm selective decrement of phase locking. The findings of the present
      experiment suggest the cortical origin of SAI that could result from the cortico
      cortical activation of GABAergic-mediated inhibition onto the corticospinal
      neurons modulated by cholinergic activation able to reducing intralaminar
      inhibition and promoting intracolumnar inhibition.

PMID- 22457461
TI  - Activity of the same motor cortex neurons during repeated experience with
      perturbed movement dynamics.
AB  - Neurons in the primary motor cortex (M1) have been shown to have persistent,
      memory-like activity following adaptation to altered movement dynamics. However,
      the techniques used to study these memory traces limited recordings to only
      single sessions lasting no more than a few hours. Here, chronically implanted
      microelectrode arrays were used to study the long-term neuronal responses to
      repeated experience with perturbing, velocity-dependent force fields. Force-field
      related neuronal activity within each session was similar to that found
      previously. That is, the directional tuning curves of the M1 neurons shifted in a
      manner appropriate to compensate for the forces. Next, the across-session
      behavior was examined. Long-term learning was evident in the performance
      improvements across multiple force-field sessions. Correlated with this change,
      the neuronal population had smaller within-session spike rate changes as
      experience with the force field increased. The smaller within-session changes
      were a result of persistent across-session shifts in directional tuning. The
      results extend the observation of memory traces of newly learned dynamics and
      provide further evidence for the role of M1 in early motor memory formation.

PMID- 22457462
TI  - Frequency-dependent effects of electrical stimulation in the globus pallidus of
      dystonia patients.
AB  - Deep brain stimulation (DBS) in the globus pallidus internus (GPi) has been shown
      to improve dystonia, a movement disorder of repetitive twisting movements and
      postures. DBS at frequencies above 60 Hz improves dystonia, but the mechanisms
      underlying this frequency dependence are unclear. In patients undergoing dual
      microelectrode mapping of the GPi, microstimulation has been shown to reduce
      neuronal firing, presumably due to synaptic GABA release. This study examined the
      effects of different microstimulation frequencies (1-100 Hz) and train length
      (0.5-20 s), with and without prior high-frequency stimulation (HFS) on neuronal
      firing and evoked field potentials (fEPs) in 13 dystonia patients. Pre-HFS, the
      average firing decreased as stimulation frequency increased and was silenced
      above 50 Hz. The average fEP amplitudes increased up to frequencies of 20-30 Hz
      but then declined and at 50 Hz, were only at 75% of baseline. In some cases,
      short latency fiber volleys and antidromic-like spikes were observed and followed
      high frequencies. Post-HFS, overall firing was reduced compared with pre-HFS, and
      the fEP amplitudes were enhanced at low frequencies, providing evidence of
      inhibitory synaptic plasticity in the GPi. In a patient with DBS electrodes
      already implanted in the GPi, recordings from four neurons in the subthalamic
      nucleus showed almost complete inhibition of firing with clinically effective but
      not clinically ineffective stimulation parameters. These data provide additional
      support for the hypothesis of stimulation-evoked GABA release from afferent
      synaptic terminals and reduction of neuronal firing during DBS and additionally,
      implicate excitation of GPi axon fibers and neurons and enhancement of inhibitory
      synaptic transmission by high-frequency GPi DBS as additional putative mechanisms
      underlying the clinical benefits of DBS in dystonia.

PMID- 22457463
TI  - Frequency tuning of the contralateral medial olivocochlear reflex in humans.
AB  - Activation of the medial olivocochlear (MOC) efferents attenuates cochlear gain
      and reduces the amplitudes of mechanical, electrical, and neural cochlear
      outputs. The functional roles of the MOC efferents are not fully understood,
      especially in humans, despite postulations that they are involved in protection
      against acoustic trauma, facilitation of transient-sound perception, etc.
      Delineating the frequency tuning properties of the MOC efferents would provide
      critical evidence to support or refute these postulated functional roles. By
      utilizing spontaneous otoacoustic emissions (SOAEs), a cochlear measure sensitive
      to MOC modulation, we systematically demonstrate in humans that the contralateral
      MOC reflex is tuned to a fixed frequency band between 500 and 1,000 Hz
      independent of SOAE frequency. Our results question the role of the MOC reflex in
      protection against acoustic trauma or facilitation of transient-sound perception.

PMID- 22457465
TI  - Time course of dynamic range adaptation in the auditory nerve.
AB  - Auditory adaptation to sound-level statistics occurs as early as in the auditory
      nerve (AN), the first stage of neural auditory processing. In addition to firing
      rate adaptation characterized by a rate decrement dependent on previous spike
      activity, AN fibers show dynamic range adaptation, which is characterized by a
      shift of the rate-level function or dynamic range toward the most frequently
      occurring levels in a dynamic stimulus, thereby improving the precision of coding
      of the most common sound levels (Wen B, Wang GI, Dean I, Delgutte B. J Neurosci
      29: 13797-13808, 2009). We investigated the time course of dynamic range
      adaptation by recording from AN fibers with a stimulus in which the sound levels
      periodically switch from one nonuniform level distribution to another (Dean I,
      Robinson BL, Harper NS, McAlpine D. J Neurosci 28: 6430-6438, 2008). Dynamic
      range adaptation occurred rapidly, but its exact time course was difficult to
      determine directly from the data because of the concomitant firing rate
      adaptation. To characterize the time course of dynamic range adaptation without
      the confound of firing rate adaptation, we developed a phenomenological "dual
      adaptation" model that accounts for both forms of AN adaptation. When fitted to
      the data, the model predicts that dynamic range adaptation occurs as rapidly as
      firing rate adaptation, over 100-400 ms, and the time constants of the two forms
      of adaptation are correlated. These findings suggest that adaptive processing in
      the auditory periphery in response to changes in mean sound level occurs rapidly
      enough to have significant impact on the coding of natural sounds.

PMID- 22457464
TI  - Molecular and functional expression of cation-chloride cotransporters in dorsal
      root ganglion neurons during postnatal maturation.
AB  - GABA depolarizes and excites central neurons during early development, becoming
      inhibitory and hyperpolarizing with maturation. This "developmental shift" occurs
      abruptly, reflecting a decrease in intracellular Cl(-) concentration ([Cl(-)](i))
      and a hyperpolarizing shift in Cl(-) equilibrium potential due to upregulation of
      the K(+)-Cl(-) cotransporter KCC2b, a neuron-specific Cl(-) extruder. In
      contrast, primary afferent neurons (PANs) are depolarized by GABA throughout
      adulthood because of expression of NKCC1, a Na(+)-K(+)-2Cl(-) cotransporter that
      accumulates Cl(-) above equilibrium. The GABA(A)-mediated depolarization of PANs
      determines presynaptic inhibition in the spinal cord, a key mechanism gating
      somatosensory information. Little is known about developmental changes in Cl(-)
      transporter expression and Cl(-) homeostasis in PANs. Whether NKCC1 is expressed
      in PANs of all phenotypes or is restricted to subpopulations (e.g., nociceptors)
      is debatable. Likewise, whether PANs express KCC2s is controversial. We
      investigated NKCC1 and K(+)-Cl(-) cotransporter expression in rat and mouse
      dorsal root ganglion (DRG) neurons with molecular methods. Using fluorescence
      imaging microscopy, we measured [Cl(-)](i) in acutely dissociated rat DRG neurons
      (P0-P21) loaded with N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide and
      classified with phenotypic markers. DRG neurons of all sizes express two NKCC1
      mRNAs, one full-length and a shorter splice variant lacking exon 21.
      Immunolabeling with validated antibodies revealed ubiquitous expression of NKCC1
      in DRG neurons irrespective of postnatal age and phenotype. As maturation
      progresses [Cl(-)](i) decreases gradually, persisting above equilibrium in >95%
      mature neurons. DRG neurons express mRNAs for KCC1, KCC3s, and KCC4, but not for
      KCC2s. Mechanisms underlying PANs' developmental changes in Cl(-) homeostasis are
      discussed and compared with those of central neurons.

PMID- 22457466
TI  - Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.
AB  - Neuroinflammation has the capacity to alter normal central nervous system (CNS)
      homeostasis and function. The objective of the present study was to examine the
      effects of an inflammatory milieu on the electrophysiological properties of
      striatal astrocyte subpopulations with a mouse bacterial brain abscess model.
      Whole cell patch-clamp recordings were performed in striatal glial fibrillary
      acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring
      abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance
      (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting
      membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2
      astrocytes were identified by negative and positive G(i) increments vs. V(m),
      respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i),
      and cell membrane capacitance that were influenced by both time after bacterial
      exposure and astrocyte proximity to the inflammatory site. Specifically, the
      percentage of A1 astrocytes was decreased immediately surrounding the
      inflammatory lesion, whereas A2 cells were increased. These changes were
      particularly evident at postinfection day 7, revealing increased cell numbers
      with an outward current component. Furthermore, RMP was inversely modified in A1
      and A2 astrocytes during neuroinflammation, and resting G(i) was increased from
      21 to 30 nS in the latter. In contrast, gap junction communication was
      significantly decreased in all astrocyte populations associated with inflamed
      tissues. Collectively, these findings demonstrate the heterogeneity of striatal
      astrocyte populations, which experience distinct electrophysiological
      modifications in response to CNS inflammation.

PMID- 22457469
TI  - Human eye-head gaze shifts preserve their accuracy and spatiotemporal trajectory
      profiles despite long-duration torque perturbations that assist or oppose head
      motion.
AB  - Humans routinely use coordinated eye-head gaze saccades to rapidly and accurately
      redirect the line of sight (Land MF. Vis Neurosci 26: 51-62, 2009). With a fixed
      body, the gaze control system combines visual, vestibular, and neck
      proprioceptive sensory information and coordinates two moving platforms, the eyes
      and head. Classic engineering tools have investigated the structure of motor
      systems by testing their ability to compensate for perturbations. When a reaching
      movement of the hand is subjected to an unexpected force field of random
      direction and strength, the trajectory is deviated and its final position is
      inaccurate. Here, we found that the gaze control system behaves differently. We
      perturbed horizontal gaze shifts with long-duration torques applied to the head
      that unpredictably either assisted or opposed head motion and very significantly
      altered the intended head trajectory. We found, as others have with brief head
      perturbations, that gaze accuracy was preserved. Unexpectedly, we found also that
      the eye compensated well--with saccadic and rollback movements--for long-duration
      head perturbations such that resulting gaze trajectories remained close to that
      when the head was not perturbed. However, the ocular compensation was best when
      torques assisted, compared with opposed, head motion. If the vestibuloocular
      reflex (VOR) is suppressed during gaze shifts, as currently thought, what caused
      invariant gaze trajectories and accuracy, early eye-direction reversals, and
      asymmetric compensations? We propose three mechanisms: a gaze feedback loop that
      generates a gaze-position error signal; a vestibular-to-oculomotor signal that
      dissociates self-generated from passively imposed head motion; and a saturation
      element that limits orbital eye excursion.

PMID- 22457468
TI  - Second-order receptive fields reveal multidigit interactions in area 3b of the
      macaque monkey.
AB  - Linear receptive field (RF) models of area 3b neurons reveal a three-component
      structure: a central excitatory region flanked by two inhibitory regions that are
      spatially and temporally nonoverlapping with the excitation. Previous studies
      also report that there is an "infield" inhibitory region throughout the neuronal
      RF, which is a nonlinear interactive (second order) effect whereby stimuli
      lagging an input to the excitatory region are suppressed. Thus linear models may
      be inaccurate approximations of the neurons' true RFs. In this study, we
      characterize the RFs of area 3b neurons, using a second-order quadratic model.
      Data were collected from 80 neurons of two awake, behaving macaque monkeys while
      a random dot pattern was scanned simultaneously across the distal pads of digits
      D2, 3, and 4. We used an iterative method derived from matching pursuit to
      identify a set of linear and nonlinear terms with significant effects on the
      neuronal response. For most neurons (65/80), the linear component of the
      quadratic RF was characterized by a single excitatory region on the dominant
      digit. Interactions within the dominant digit were characterized by two quadratic
      filters that capture the spatial aspects of the interactive infield inhibition.
      Interactions between the dominant (most responsive) digit and its adjacent
      digit(s) formed the largest class of cross-digit interactions. The results
      demonstrate that a significant part of area 3b responses is due to nonlinear
      mechanisms, and furthermore, the data support the notion that area 3b neurons
      have "nonclassical RF"-like input from adjacent fingers, indicating that area 3b
      plays a role in integrating shape inputs across digits.

PMID- 22457467
TI  - Dynamic afferent synapses to decision-making networks improve performance in
      tasks requiring stimulus associations and discriminations.
AB  - Animals must often make opposing responses to similar complex stimuli. Multiple
      sensory inputs from such stimuli combine to produce stimulus-specific patterns of
      neural activity. It is the differences between these activity patterns, even when
      small, that provide the basis for any differences in behavioral response. In the
      present study, we investigate three tasks with differing degrees of overlap in
      the inputs, each with just two response possibilities. We simulate behavioral
      output via winner-takes-all activity in one of two pools of neurons forming a
      biologically based decision-making layer. The decision-making layer receives
      inputs either in a direct stimulus-dependent manner or via an intervening
      recurrent network of neurons that form the associative layer, whose activity
      helps distinguish the stimuli of each task. We show that synaptic facilitation of
      synapses to the decision-making layer improves performance in these tasks,
      robustly increasing accuracy and speed of responses across multiple
      configurations of network inputs. Conversely, we find that synaptic depression
      worsens performance. In a linearly nonseparable task with exclusive-or logic, the
      benefit of synaptic facilitation lies in its superlinear transmission: effective
      synaptic strength increases with presynaptic firing rate, which enhances the
      already present superlinearity of presynaptic firing rate as a function of
      stimulus-dependent input. In linearly separable single-stimulus discrimination
      tasks, we find that facilitating synapses are always beneficial because synaptic
      facilitation always enhances any differences between inputs. Thus we predict that
      for optimal decision-making accuracy and speed, synapses from sensory or
      associative areas to decision-making or premotor areas should be facilitating.

PMID- 22457471
TI  - European researchers are urged to do more trials in children, conference hears.

PMID- 22457470
TI  - Macaque V1 representations in natural and reduced visual contexts: spatial and
      temporal properties and influence of saccadic eye movements.
AB  - Vision in natural situations is different from the paradigms generally used to
      study vision in the laboratory. In natural vision, stimuli usually appear in a
      receptive field as the result of saccadic eye movements rather than suddenly
      flashing into view. The stimuli themselves are rich with meaningful and
      recognizable objects rather than simple abstract patterns. In this study we
      examined the sensitivity of neurons in macaque area V1 to saccades and to complex
      background contexts. Using a variety of visual conditions, we find that natural
      visual response patterns are unique. Compared with standard laboratory
      situations, in more natural vision V1 responses have longer latency, slower time
      course, delayed orientation selectivity, higher peak selectivity, and lower
      amplitude. Furthermore, the influences of saccades and background type (complex
      picture vs. uniform gray) interact to give a distinctive, and presumably more
      natural, response pattern. While in most of the experiments natural images were
      used as background, we find that similar synthetic unnatural background stimuli
      produce nearly identical responses (i.e., complexity matters more than
      "naturalness"). These findings have important implications for our understanding
      of vision in more natural situations. They suggest that with the saccades used to
      explore complex images, visual context ("surround effects") would have a far
      greater effect on perception than in standard experiments with stimuli flashed on
      a uniform background. Perceptual thresholds for contrast and orientation should
      also be significantly different in more natural situations.

PMID- 22457472
TI  - European Medicines Agency is to tighten up on advisers' conflicts of interest.

PMID- 22457473
TI  - NHS costs could rise and emergency care suffer under health bill, says leaked
      risk register.

PMID- 22457474
TI  - Biological, clinical, and psychosocial correlates at the interface of cancer and
      aging research.
AB  - In September 2010, the Cancer and Aging Research Group, in collaboration with the
      National Cancer Institute and the National Institute on Aging, conducted the
      first of three planned conferences to discuss research methodology to generate
      the highest quality research in older adults with cancer and then disseminate
      these findings among those working in the fields of cancer and aging. Conference
      speakers discussed the current level of research evidence in geriatric oncology,
      outlined the current knowledge gaps, and put forth principles for research
      designs and strategies that would address these gaps within the next 10 years. It
      was agreed that future oncology research trials that enroll older adults should
      include: (1) improved standardized geriatric assessment of older oncology
      patients, (2) substantially enhanced biological assessment of older oncology
      patients, (3) specific trials for the most vulnerable and/or those older than 75
      years, and (4) research infrastructure that specifically targets older adults and
      substantially strengthened geriatrics and oncology research collaborations. This
      initial conference laid the foundation for the next two meetings, which will
      address the research designs and collaborations needed to enhance therapeutic and
      intervention trials in older adults with cancer.

PMID- 22457475
TI  - Body mass index and risk of lung cancer among never, former, and current smokers.
AB  - BACKGROUND: Although obesity has been directly linked to the development of many
      cancers, many epidemiological studies have found that body mass index (BMI)--a
      surrogate marker of obesity--is inversely associated with the risk of lung
      cancer. These studies are difficult to interpret because of potential confounding
      by cigarette smoking, a major risk factor for lung cancer that is associated with
      lower BMI. METHODS: We prospectively examined the association between BMI and the
      risk of lung cancer among 448 732 men and women aged 50-71 years who were
      recruited during 1995-1996 for the National Institutes of Health-AARP Diet and
      Health Study. BMI was calculated based on the participant's self-reported height
      and weight on the baseline questionnaire. We identified 9437 incident lung
      carcinomas (including 415 in never smokers) during a mean follow-up of 9.7 years
      through 2006. Multivariable Cox proportional hazards regression models were used
      to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with
      adjustment for lung cancer risk factors, including smoking status. To address
      potential bias due to preexisting undiagnosed disease, we excluded potentially
      unhealthy participants in sensitivity analyses. All statistical tests were two
      sided. RESULTS: The crude incidence rate of lung cancer over the study follow-up
      period was 233 per 100 000 person-years among men and 192 per 100 000 person
      years among women. BMI was inversely associated with the risk of lung cancer
      among both men and women (BMI >=35 vs 22.5-24.99 kg/m(2): HR = 0.81, 95% CI =
      0.70 to 0.94 and HR = 0.73, 95% CI = 0.61 to 0.87, respectively). The inverse
      association was restricted to current and former smokers and was stronger after
      adjustment for smoking. Among smokers, the inverse association persisted even
      after finely stratifying on smoking status, time since quitting smoking, and
      number of cigarettes smoked per day. Sensitivity analyses did not support the
      possibility that the inverse association was due to prevalent undiagnosed
      disease. CONCLUSIONS: Our results suggest that a higher BMI is associated with a
      reduced risk of lung cancer in current and former smokers. Our inability to
      attribute the inverse association between BMI and the risk of lung cancer to
      residual confounding by smoking or to bias suggests the need for considering
      other explanations.

PMID- 22457476
TI  - Therapeutic potential of amanitin-conjugated anti-epithelial cell adhesion
      molecule monoclonal antibody against pancreatic carcinoma.
AB  - BACKGROUND: Human epithelial cell adhesion molecule (EpCAM) is overexpressed in
      many cancers. Anti-EpCAM antibodies have shown promise in preclinical studies,
      but showed no tumor regression in a recent phase II clinical trial. Therefore, we
      generated a novel anti-EpCAM antibody-drug conjugate and assessed whether it
      showed enhanced antitumor effects. METHODS: Chemical cross-linking was conducted
      to covalently conjugate alpha-amanitin, a toxin known to inhibit DNA
      transcription, with chiHEA125, a chimerized anti-EpCAM monoclonal antibody, to
      generate the antibody-drug conjugate alpha-amanitin-glutarate-chiHEA125
      (chiHEA125-Ama). Antiproliferative activity of chiHEA125-Ama was tested in human
      pancreatic (BxPc-3 and Capan-1), colorectal (Colo205), breast (MCF-7), and bile
      duct (OZ) cancer cell lines in vitro using [(3)H]-thymidine incorporation assay.
      Antitumor activity of chiHEA125-Ama was assessed in vivo in immunocompromised
      mice bearing subcutaneous human BxPc-3 pancreatic carcinoma xenograft tumors (n =
      66 mice). Cell proliferation and apoptosis were evaluated in xenograft tumors by
      immunohistochemistry. All statistical tests were two-sided. RESULTS: In all cell
      lines, chiHEA125-Ama reduced cell proliferation (mean half maximal inhibitory
      concentration [IC(50)] = 2.5 * 10(-10) to 5.4 * 10(-12) M). A single dose of
      chiHEA125-Ama inhibited BxPc-3 xenograft tumor growth (chiHEA125 [control, n = 4
      mice] vs. chiHEA125-Ama [n = 6 mice], dose of 15 mg/kg with respect to IgG and 50
      MUg/kg with respect to alpha-amanitin, mean relative increase in tumor volume on
      day 16 = 884% vs. -79%, difference = 963%, 95% CI = 582% to 1344%, P = .019). Two
      higher doses of chiHEA125-Ama (100 MUg/kg with respect to alpha-amanitin),
      administered 1 week apart (n = 10 mice per group), led to complete tumor
      regression in nine of 10 (90%) mice compared with chiHEA125, during the
      observation period of 16 days; increased apoptosis and reduced cell proliferation
      were observed in mice treated with chiHEA125-Ama. CONCLUSION: This preclinical
      study suggests that anti-EpCAM antibody conjugates with alpha-amanitin have the
      potential to be highly effective therapeutic agents for pancreatic carcinomas and
      various EpCAM-expressing malignancies.

PMID- 22457477
TI  - A qualitative evaluation of general practitioners' perceptions regarding access
      to medicines in New Zealand.
AB  - OBJECTIVE: The objective of this study was to evaluate general practitioners'
      (GPs) perceptions regarding access to medicines in New Zealand. DESIGN:
      Qualitative. SETTING: Primary care. PARTICIPANTS: GPs. MAIN OUTCOME MEASURES:
      GPs' views and perceptions. RESULTS: GPs were of the view that the current range
      of medicines available in New Zealand was reasonable; however, it was
      acknowledged that there were some drugs that patients were missing out on. When
      considering the range of subsidised medicines available in New Zealand, some GPs
      felt that there had been an improvement over recent years. It was highlighted
      that unexpected funding changes could create financial barriers for some patients
      and that administrative procedures and other complexities created barriers in
      receiving a subsidy for restricted medicines. GPs also reported problems with the
      availability and sole supply of certain medicines and claimed that switching from
      a branded medicine to its generic counterpart could be disruptive for patients.
      CONCLUSIONS: The research concluded that although there were some issues with the
      availability of certain drugs, most GPs were satisfied with the broader access to
      medicines situation in New Zealand. This view is to contrary to the situation
      presented by the pharmaceutical industry. The issues around sole supply, the use
      of generic medicines and the administrative barriers regarding funding of
      medicines could be improved with better systems. The current work provides a
      solid account of what GPs see as the advantages and disadvantages of the current
      system and how they balance these demands in practice.

PMID- 22457478
TI  - International collaboration: a retrospective study examining the survival of
      Irish citizens following lung transplantation in both the UK and Ireland.
AB  - OBJECTIVE: Prior to 2005, Irish citizens had exclusively availed of lung
      transplantation services in the UK. Since 2005, lung transplantation has been
      available to these patients in both the UK and Ireland. We aimed to evaluate the
      outcomes of Irish patients undergoing lung transplantation in both the UK and
      Ireland. DESIGN: We retrospectively examined the outcome of Irish patients
      transplanted in the UK and Ireland. Lung allocation score (LAS) was used as a
      marker of disease severity. RESULTS: A total of 134 patients have undergone
      transplantation. 102 patients underwent transplantation in the UK and 32 patients
      in Ireland. In total, 52% were patients with cystic fibrosis, 19% had emphysema
      and 15% had idiopathic pulmonary fibrosis. In Ireland, 44% of the patients
      suffered from idiopathic pulmonary fibrosis, 31% had emphysema and 16% had cystic
      fibrosis. A total of 96 double sequential transplants and 38 single transplants
      have been performed. LAS of all patients undergoing lung transplantation was 37.8
      (+/-1.02). The mean LAS for patients undergoing lung transplantation in Ireland
      was 44.7 (+/-3.1), and 35 (+/-0.4) for patients undergoing lung transplantation
      in the UK (p<0.05). The 5-year survival of all Irish citizens who had undergone
      lung transplantation was 73%. The 5-year survival of Irish patients transplanted
      in the UK was 69% and in Ireland was 91% and 73% at 5.01 years. CONCLUSIONS:
      International collaboration can be achieved, as evidenced by the favourable
      outcomes seen in Irish citizens who undergo lung transplantation in both the UK
      and Ireland. Irish citizens undergoing lung transplantation in Ireland have a
      higher LAS score. Despite excellent outcomes, an intention-to-treat analysis of
      the treatment utility (transplant) indicates the limited effectiveness of lung
      transplantation in Ireland and emphasises the need for increased rates of lung
      transplantation.

PMID- 22457479
TI  - Have the public's expectations for antibiotics for acute uncomplicated
      respiratory tract infections changed since the H1N1 influenza pandemic? A
      qualitative interview and quantitative questionnaire study.
AB  - OBJECTIVE: To investigate the effect of the H1N1 influenza pandemic on the
      public's expectations for a general practice consultation and antibiotic for
      acute respiratory illness. DESIGN: Mixed methods. PARTICIPANTS: Qualitative
      interviews: 17 participants with acute respiratory tract infection (RTI) visiting
      English pharmacies. Face-to-face survey: about 1700 adults aged 15 years and
      older were recruited from households in England in January 2008, 2009 and 2011.
      RESULTS: The qualitative data indicated that the general public had either
      forgotten about the 'swine flu' (H1N1 influenza) pandemic or it did not concern
      them as it had not affected them directly or affected their management of their
      current RTI illness. Between 2009 and 2011, we found that there was little or no
      change in people's expectations for antibiotics for runny nose, colds, sore
      throat or cough, but people's expectations for antibiotics for flu increased (26%
      32%, p=0.004). Of the 1000 respondents in 2011 with an RTI in the previous 6
      months, 13% reported that they took care of themselves without contacting their
      general practitioners and would not have done so before the pandemic, 9% reported
      that they had contacted their doctor's surgery and would not have done so before
      the pandemic and 0.6% stated that they had asked for antibiotics and would not
      have done so before the pandemic. In 2011, of 123 respondents with a young child
      (0-4 years) having an RTI in the previous 6 months, 7.4% requested antibiotics
      and would not have done so before the pandemic. Unprompted, 20% of respondents
      thought Tamiflu(c) (oseltamivir) was a vaccine. CONCLUSIONS: Expectations of the
      general public for a consultation or antibiotics with an RTI are similar now to
      before the H1N1 influenza pandemic; therefore, public antibiotic campaign
      messages and general practice advice to patients can remain unchanged. Parents
      with young children and those with personal experience of the H1N1 influenza are
      more likely to consult and will need more reassurance. The public need more
      education about Tamiflu(c).

PMID- 22457480
TI  - Time trends in STEMI--improved treatment and outcome but still a gender gap: a
      prospective observational cohort study from the SWEDEHEART register.
AB  - OBJECTIVE: In ST elevation myocardial infarction women received less evidence
      based medicine and had worse outcome during the fibrinolytic era. With the shift
      to primary percutaneous coronary intervention (pPCI) as preferred reperfusion
      strategy, the authors aimed to investigate whether these gender differences has
      diminished. DESIGN, SETTING AND PARTICIPANTS: Cohort study including consecutive
      ST elevation myocardial infarction patients registered 1998-2000 (n=15 697) and
      2004-2006 (n=14 380) in the Register of Information and Knowledge about Swedish
      Heart Intensive care Admissions. OUTCOME MEASURES: 1. Use of evidence-based
      medicine such as reperfusion therapy (pPCI or fibrinolysis) and evidence-based
      drugs at discharge. 2. Inhospital and 1-year mortality. RESULTS: Of those who got
      reperfusion therapy, pPCI was the choice in 9% in the early period compared with
      68% in the late period. In the early period, reperfusion therapy was given to 63%
      of women versus 71% of men, p<0.001. Corresponding figures in the late period
      were 64% vs 75%, p<0.001. After multivariable adjustments, the ORs (women vs men)
      were 0.86 (95% CI 0.78 to 0.94) in the early and 0.80 (95% CI 0.73 to 0.89) in
      the late period. As regards evidence-based secondary preventive drugs at
      discharge in hospital survivors (platelet inhibitors, statins, ACE
      inhibitors/angiotensin receptor blockers and beta-blockers), there were small
      gender differences in the early period. In the late period, women had 14%-25%
      less chance of receiving these drugs, OR 0.75 (95% CI 0.68 to 0.81) through 0.86
      (95% CI 0.73 to 1.00). In both periods, multivariable-adjusted inhospital
      mortality was higher in women, OR 1.18 (95% CI 1.02 to 1.36) and 1.21 (1.00 to
      1.46). One-year mortality was gender equal, HR 0.95 (95% CI 0.87 to 1.05) and
      0.96 (0.86 to 1.08), after adding evidence-based medicine to the multivariable
      adjustments. CONCLUSION: In spite of an intense gender debate, focus on guideline
      adherence and the change in reperfusion strategy, the last decade gender
      differences in use of reperfusion therapy and evidence-based therapy at discharge
      did not decline during the study period, rather the opposite. Moreover, higher
      mortality in women persisted.

PMID- 22457481
TI  - Trends in the coverage of 'universal' child health reviews: observational study
      using routinely available data.
AB  - OBJECTIVES: Universally offered child health reviews form the backbone of the UK
      child health programme. The reviews assess children's health, development and
      well-being and facilitate access to additional support as required. The number of
      reviews offered per child has been reduced over recent years to allow more
      flexible provision of support to families in need: equitable coverage of the
      remaining reviews is therefore particularly important. This study assessed the
      coverage of universal child health reviews, with an emphasis on trends over time
      and inequalities in coverage by deprivation. DESIGN: Assessment of the coverage
      of child health reviews by area-based deprivation using routinely available data.
      Supplementary audit of the quality of the routine data source used. SETTING:
      Scotland. PARTICIPANTS: Two cohorts of around 40 000 children each. The cohorts
      were born in 1998/1999 and 2007/2008 and eligible for the previous programme of
      five and the current programme of two preschool reviews, respectively. OUTCOME
      MEASURES: Coverage of the specified child health reviews for the whole cohorts
      and by deprivation. RESULTS: Coverage of the 10 day review is high (99%), but it
      progressively declines for reviews at older ages (86% for the 39-42 month
      review). Coverage is lower in children living in the most deprived areas for all
      reviews, and the discrepancy progressively increases for reviews at older ages
      (78% and 92% coverage for the 39-42 month review in most and least deprived
      groups). Coverage has been stable over time: it has not increased for the
      remaining reviews after reduction in the number of reviews provided. CONCLUSIONS:
      The inverse care law continues to operate in relation to 'universal' child health
      reviews. Equitable uptake of reviews is important to ensure maximum likely impact
      on inequalities in children's outcomes.

PMID- 22457482
TI  - Leadership competencies for medical education and healthcare professions:
      population-based study.
AB  - OBJECTIVE: To identify and empirically investigate the dimensions of leadership
      in medical education and healthcare professions. DESIGN: A population-based
      design with a focus group and a survey were used to identify the perceived
      competencies for effective leadership in medical education. SETTING: The focus
      group, consisting of five experts from three countries (Austria n=1; Germany n=2;
      Switzerland n=2), was conducted (all masters of medical education), and the
      survey was sent to health professionals from medical schools and teaching
      hospitals in six countries (Austria, Canada, Germany, Switzerland, the UK and the
      USA). PARTICIPANTS: The participants were educators, physicians, nurses and other
      health professionals who held academic positions in medical education. A total of
      229 completed the survey: 135 (59.0%) women (mean age=50.3 years) and 94 (41.0%)
      men (mean age=51.0 years). MEASURES: A 63-item survey measuring leadership
      competencies was developed and administered via electronic mail to participants.
      RESULTS: Exploratory principal component analyses yielded five factors accounting
      for 51.2% of the variance: (1) social responsibility, (2) innovation, (3) self
      management, (4) task management and (5) justice orientation. There were
      significant differences between physicians and other health professionals on some
      factors (Wilk's lambda=0.93, p<0.01). Social responsibility was rated higher by
      other health professionals (M=71.09) than by physicians (M=67.12), as was
      innovation (health professionals M=80.83; physicians M=76.20) and justice
      orientation (health professionals M=21.27; physicians M=20.46). CONCLUSIONS: The
      results of the principal component analyses support the theoretical
      meaningfulness of these factors, their coherence, internal consistency and
      parsimony in explaining the variance of the data. Although there are some between
      group differences, the competencies appear to be stable and coherent.

PMID- 22457483
TI  - First robotic tracheal intubations in humans using the Kepler intubation system.
AB  - BACKGROUND: Intubation is one of the most important anaesthetic skills. We
      developed a robotic intubation system (Kepler intubation system, KIS) for oral
      tracheal intubation. METHODS: In this pilot study, 12 patients were enrolled
      after approval of the local Ethics board and written informed consent. The KIS
      consists of four main components: a ThrustMaster T.Flight Hotas X joystick
      (Guillemot Inc., New York, NY, USA), a JACO robotic arm (Kinova Rehab, Montreal,
      QC, Canada), a Pentax AWS video laryngoscope (Ambu A/S, Ballerup, Denmark), and a
      software control system. The joystick allows simulation of the wrist or arm
      movements of a human operator. The success rate of intubation and intubation
      times were measured. RESULTS: Eleven men and one woman aged 66 yr were included
      in this study. Intubation was successful in all but one patient using KIS at a
      total time of [median (inter-quartile range; range)] 93 (87, 109; 76, 153) s; in
      one patient, fogging of the video laryngoscope prevented intubation using KIS.
      CONCLUSIONS: We present the first human testing of a robotic intubation system
      for oral tracheal intubation. The success rate was high at 91%. Future studies
      are needed to assess the performance and safety of such a system.

PMID- 22457484
TI  - Keratan sulfate proteoglycans in plasticity and recovery after spinal cord
      injury.

PMID- 22457485
TI  - Bidirectional relationship between functional connectivity and amyloid-beta
      deposition in mouse brain.
AB  - Brain region-specific deposition of extracellular amyloid plaques principally
      composed of aggregated amyloid-beta (Abeta) peptide is a pathological signature
      of Alzheimer's disease (AD). Recent human neuroimaging data suggest that resting
      state functional connectivity strength is reduced in patients with AD,
      cognitively normal elderly harboring elevated amyloid burden, and in advanced
      aging. Interestingly, there exists a striking spatial correlation between
      functional connectivity strength in cognitively normal adults and the location of
      Abeta plaque deposition in AD. However, technical limitations have heretofore
      precluded examination of the relationship between functional connectivity, Abeta
      deposition, and normal aging in mouse models. Using a novel functional
      connectivity optical intrinsic signal (fcOIS) imaging technique, we demonstrate
      that Abeta deposition is associated with significantly reduced bilateral
      functional connectivity in multiple brain regions of older APP/PS1 transgenic
      mice. The amount of Abeta deposition in each brain region was associated with the
      degree of local, age-related bilateral functional connectivity decline. Normal
      aging was associated with reduced bilateral functional connectivity specifically
      in retrosplenial cortex. Furthermore, we found that the magnitude of regional
      bilateral functional correlation in young APP/PS1 mice before Abeta plaque
      formation was proportional to the amount of region-specific plaque deposition
      seen later in older APP/PS1 mice. Together, these findings suggest that Abeta
      deposition and normal aging are associated with region-specific disruption of
      functional connectivity and that the magnitude of local bilateral functional
      connectivity predicts regional vulnerability to subsequent Abeta deposition in
      mouse brain.

PMID- 22457487
TI  - The mode of retinal presynaptic inhibition switches with light intensity.
AB  - Excitatory amino acid transporters (EAATs) terminate signaling in the CNS by
      clearing released glutamate. Glutamate also evokes an EAAT-mediated Cl(-)
      current, but its role in CNS signaling is poorly understood. We show in mouse
      retina that EAAT-mediated Cl(-) currents that were evoked by light inhibit rod
      pathway signaling. EAATs reside on rod bipolar cell axon terminals where GABA and
      glycine receptors also mediate light-evoked inhibition. We found that the mode of
      inhibition depended on light intensity. Dim light evoked GABAergic and
      glycinergic inhibition with rapid kinetics and a large spatial extent. Bright
      light evoked predominantly EAAT-mediated inhibition with slow kinetics and a
      small spatial extent. The switch to EAAT-mediated signaling in bright light
      supplements receptor-mediated signaling to expand the dynamic range of inhibition
      and contributes to the transition from rod to cone signaling by suppressing rod
      pathway signaling in bright light conditions.

PMID- 22457488
TI  - The lhx2 transcription factor controls thalamocortical axonal guidance by
      specific regulation of robo1 and robo2 receptors.
AB  - The assembly of neural circuits is dependent upon the generation of specific
      neuronal subtypes, each subtype displaying unique properties that direct the
      formation of selective connections with appropriate target cells. Actions of
      transcription factors in neural progenitors and postmitotic cells are key
      regulators in this process. LIM-homeodomain transcription factors control crucial
      aspects of neuronal differentiation, including subtype identity and axon
      guidance. Nonetheless, their regulation during development is poorly understood
      and the identity of the downstream molecular effectors of their activity remains
      largely unknown. Here, we demonstrate that the Lhx2 transcription factor is
      dynamically regulated in distinct pools of thalamic neurons during the
      development of thalamocortical connectivity in mice. Indeed, overexpression of
      Lhx2 provokes defective thalamocortical axon guidance in vivo, while specific
      conditional deletion of Lhx2 in the thalamus produces topographic defects that
      alter projections from the medial geniculate nucleus and from the caudal
      ventrobasal nucleus in particular. Moreover, we demonstrate that Lhx2 influences
      axon guidance and the topographical sorting of axons by regulating the expression
      of Robo1 and Robo2 guidance receptors, which are essential for these axons to
      establish correct connections in the cerebral cortex. Finally, augmenting Robo1
      function restores normal axon guidance in Lhx2-overexpressing neurons. By
      regulating axon guidance receptors, such as Robo1 and Robo2, Lhx2 differentially
      regulates the axon guidance program of distinct populations of thalamic neurons,
      thus enabling the establishment of specific neural connections.

PMID- 22457486
TI  - Synergy between electrical coupling and membrane properties promotes strong
      synchronization of neurons of the mesencephalic trigeminal nucleus.
AB  - Electrical synapses are known to form networks of extensively coupled neurons in
      various regions of the mammalian brain. The mesencephalic trigeminal (MesV)
      nucleus, formed by the somata of primary afferents originating in jaw-closing
      muscles, constitutes one of the first examples supporting the presence of
      electrical synapses in the mammalian CNS; however, the properties, functional
      organization, and developmental emergence of electrical coupling within this
      structure remain unknown. By combining electrophysiological, tracer coupling, and
      immunochemical analysis in brain slices of rat and mouse, we found that coupling
      is mostly restricted to pairs or small clusters of MesV neurons. Electrical
      transmission is supported by connexin36 (Cx36)-containing gap junctions at somato
      somatic contacts where only a small proportion of channels appear to be open
      (~0.1%). In marked contrast with most brain structures, coupling among MesV
      neurons increases with age, such that it is absent during early development and
      appears at postnatal day 8. Interestingly, the development of coupling parallels
      the development of intrinsic membrane properties responsible for repetitive
      firing in these neurons. We found that, acting together, sodium and potassium
      conductances enhance the transfer of signals with high-frequency content via
      electrical synapses, leading to strong spiking synchronization of the coupled
      neurons. Together, our data indicate that coupling in the MesV nucleus is
      restricted to mostly pairs of somata between which electrical transmission is
      supported by a surprisingly small fraction of the channels estimated to be
      present, and that coupling synergically interacts with specific membrane
      conductances to promote synchronization of these neurons.

PMID- 22457489
TI  - Network analysis of corticocortical connections reveals ventral and dorsal
      processing streams in mouse visual cortex.
AB  - Much of the information used for visual perception and visually guided actions is
      processed in complex networks of connections within the cortex. To understand how
      this works in the normal brain and to determine the impact of disease, mice are
      promising models. In primate visual cortex, information is processed in a dorsal
      stream specialized for visuospatial processing and guided action and a ventral
      stream for object recognition. Here, we traced the outputs of 10 visual areas and
      used quantitative graph analytic tools of modern network science to determine,
      from the projection strengths in 39 cortical targets, the community structure of
      the network. We found a high density of the cortical graph that exceeded that
      shown previously in monkey. Each source area showed a unique distribution of
      projection weights across its targets (i.e., connectivity profile) that was well
      fit by a lognormal function. Importantly, the community structure was strongly
      dependent on the location of the source area: outputs from medial/anterior
      extrastriate areas were more strongly linked to parietal, motor, and limbic
      cortices, whereas lateral extrastriate areas were preferentially connected to
      temporal and parahippocampal cortices. These two subnetworks resemble dorsal and
      ventral cortical streams in primates, demonstrating that the basic layout of
      cortical networks is conserved across species.

PMID- 22457490
TI  - HDAC6 regulates glucocorticoid receptor signaling in serotonin pathways with
      critical impact on stress resilience.
AB  - Genetic variations in certain components of the glucocorticoid receptor (GR)
      chaperone complex have been associated with the development of stress-related
      affective disorders and individual variability in therapeutic responses to
      antidepressants. Mechanisms that link GR chaperoning and stress susceptibility
      are not well understood. Here, we show that the effects of glucocorticoid
      hormones on socioaffective behaviors are critically regulated via reversible
      acetylation of Hsp90, a key component of the GR chaperone complex. We provide
      pharmacological and genetic evidence indicating that the cytoplasmic lysine
      deacetylase HDAC6 controls Hsp90 acetylation in the brain, and thereby modulates
      Hsp90-GR protein-protein interactions, as well as hormone- and stress-induced GR
      translocation, with a critical impact on GR downstream signaling and behavior.
      Pet1-Cre-driven deletion of HDAC6 in serotonin neurons, the densest HDAC6
      expressing cell group in the mouse brain, dramatically reduced acute anxiogenic
      effects of the glucocorticoid hormone corticosterone in the open-field, elevated
      plus maze, and social interaction tests. Serotonin-selective depletion of HDAC6
      also blocked the expression of social avoidance in mice exposed to chronic social
      defeat and concurrently prevented the electrophysiological and morphological
      changes induced, in serotonin neurons, by this murine model of traumatic stress.
      Together, these results identify HDAC6 inhibition as a potential new strategy for
      proresilience and antidepressant interventions through regulation of the Hsp90-GR
      heterocomplex and focal prevention of GR signaling in serotonin pathways. Our
      data thus uncover an alternate mechanism by which pan-HDAC inhibitors may
      regulate stress-related behaviors independently of their action on histones.

PMID- 22457491
TI  - Wakefulness affects synaptic and network activity by increasing extracellular
      astrocyte-derived adenosine.
AB  - Loss of sleep causes an increase in sleep drive and deficits in hippocampal
      dependent memory. Both of these responses are thought to require activation of
      adenosine A1 receptors (adorA1Rs) and release of transmitter molecules including
      ATP, which is rapidly converted to adenosine in the extracellular space, from
      astrocytes in a process termed gliotransmission. Although it is increasingly
      clear that astrocyte-derived adenosine plays an important role in driving the
      homeostatic sleep response and the effects of sleep loss on memory (Halassa et
      al., 2009; Florian et al., 2011), previous studies have not determined whether
      the concentration of this signaling molecule increases in response to
      wakefulness. Here, we show that the level of adorA1R activation increases in
      response to wakefulness in mice (Mus musculus). We found that this increase
      affected synaptic transmission in the hippocampus and modulated network activity
      in the cortex. Direct biosensor-based measurement of adenosine showed that the
      net extracellular concentration of this transmitter increased in response to
      normal wakefulness and sleep deprivation. Genetic inhibition of gliotransmission
      prevented this increase and attenuated the wakefulness-dependent changes in
      synaptic and network regulation by adorA1R. Consequently, we conclude that
      wakefulness increases the level of extracellular adenosine in the hippocampus and
      that this increase requires the release of transmitters from astroctyes.

PMID- 22457492
TI  - Chondrolectin mediates growth cone interactions of motor axons with an
      intermediate target.
AB  - The C-type lectin chondrolectin (chodl) represents one of the major gene products
      dysregulated in spinal muscular atrophy models in mice. However, to date, no
      function has been determined for the gene. We have identified chodl and other
      novel genes potentially involved in motor axon differentiation, by expression
      profiling of transgenically labeled motor neurons in embryonic zebrafish. To
      enrich the profile for genes involved in differentiation of peripheral motor
      axons, we inhibited the function of LIM-HDs (LIM homeodomain factors) by
      overexpression of a dominant-negative cofactor, thereby rendering labeled axons
      unable to grow out of the spinal cord. Importantly, labeled cells still exhibited
      axon growth and most cells retained markers of motor neuron identity. Functional
      tests of chodl, by overexpression and knockdown, confirm crucial functions of
      this gene for motor axon growth in vivo. Indeed, knockdown of chodl induces
      arrest or stalling of motor axon growth at the horizontal myoseptum, an
      intermediate target and navigational choice point, and reduced muscle innervation
      at later developmental stages. This phenotype is rescued by chodl overexpression,
      suggesting that correct expression levels of chodl are important for interactions
      of growth cones of motor axons with the horizontal myoseptum. Combined, these
      results identify upstream regulators and downstream functions of chodl during
      motor axon growth.

PMID- 22457494
TI  - Understanding how the brain changes its mind: microstimulation in the macaque
      frontal eye field reveals how saccade plans are changed.
AB  - Accumulator models that integrate incoming sensory information into motor plans
      provide a robust framework to understand decision making. However, their
      applicability to situations that demand a change of plan raises an interesting
      problem for the brain. This is because interruption of the current motor plan
      must occur by a competing motor plan, which is necessarily weaker in strength. To
      understand how changes of mind get expressed in behavior, we used a version of
      the double-step task called the redirect task, in which monkeys were trained to
      modify a saccade plan. We microstimulated the frontal eye fields during redirect
      behavior and systematically measured the deviation of the evoked saccade from the
      response field to causally track the changing saccade plan. Further, to identify
      the underlying mechanisms, eight different computational models of redirect
      behavior were assessed. It was observed that the model that included an
      independent, spatially specific inhibitory process, in addition to the two
      accumulators representing the preparatory processes of initial and final motor
      plans, best predicted the performance and the pattern of saccade deviation
      profile in the task. Such an inhibitory process suppressed the preparation of the
      initial motor plan, allowing the final motor plan to proceed unhindered. Thus,
      changes of mind are consistent with the notion of a spatially specific,
      inhibitory process that inhibits the current inappropriate plan, allowing
      expression of the new plan.

PMID- 22457495
TI  - A role for perirhinal cortex in memory for novel object-context associations.
AB  - It is debated whether functional divisions between structures in the medial
      temporal lobe (MTL), in particular the perirhinal cortex (PrC) and hippocampus
      (HC), are best conceptualized according to memory process (Diana et al., 2007;
      Ranganath, 2010; Wixted et al., 2010) or stimulus category (Graham et al., 2010).
      In the former account, PrC is critical for item familiarity but not recollection
      of associations between items and their contexts (which is instead dependent upon
      the HC; Ranganath et al., 2004). In the latter theory, complex object
      representations in PrC are capable of supporting memory for objects as well as
      for object-context associations, particularly when there is a demand to
      discriminate between highly visually similar objects (Cowell et al., 2010). To
      adjudicate between these accounts, human participants were scanned while making
      two different judgments about visually presented objects (is the object common or
      uncommon, or does the object have more edges or curves). In a subsequent,
      unscanned, retrieval phase, participants made item (old/new) followed by context
      (encoding task) judgments about previously seen and novel objects. Neural
      activity at encoding was separated according to the accuracy of the retrieval
      judgments. PrC activity predicted successful item-context judgments, a result
      that remained when item-memory strength was equated across objects for which the
      context was remembered or forgotten. These data imply that the function of PrC
      goes beyond processing item-based memory information, contributing additionally
      to memory for item-context associations when the stimuli are objects (Graham et
      al., 2010).

PMID- 22457493
TI  - Netrin/DCC signaling guides olfactory sensory axons to their correct location in
      the olfactory bulb.
AB  - Olfactory sensory neurons expressing particular olfactory receptors project to
      specific reproducible locations within the bulb. The axonal guidance cues that
      organize this precise projection pattern are only beginning to be identified. To
      aid in their identification and characterization, we generated a transgenic
      zebrafish line, OR111-7:IRES:Gal4, in which a small subset of olfactory sensory
      neurons is labeled. Most sensory neurons expressing the OR111-7 transgene project
      to a specific location within the bulb, the central zone protoglomerulus, while a
      smaller number project to the lateral glomerulus 1 protoglomerulus. Inhibiting
      Netrin/DCC (deleted in colorectal cancer) signaling perturbs the ability of OR111
      7-expressing axons to enter the olfactory bulb and alters their patterns of
      termination within the bulb. The Netrin receptor DCC is expressed in olfactory
      sensory neurons around the time that they elaborate their axons, netrin1a is
      expressed near the medial-most margin of the olfactory bulb, and netrin1b is
      expressed within the ventral region of the bulb. Loss of Netrin/DCC signaling
      components causes some OR111-7-expressing sensory axons to wander posteriorly
      after exiting the olfactory pit, away from netrin-expressing areas in the bulb.
      OR111-7-expressing axons that enter the bulb target the central zone less
      precisely than normal, spreading away from netrin-expressing regions. These
      pathfinding errors can be corrected by the reexpression of DCC within OR111-7
      transgene-expressing neurons in DCC morphant embryos. These findings implicate
      Netrins as the only known attractants for olfactory sensory neurons, first
      drawing OR111-7-expressing axons into the bulb and then into the ventromedially
      positioned central zone protoglomerulus.

PMID- 22457496
TI  - Eye movements modulate the spatiotemporal dynamics of word processing.
AB  - Active reading requires coordination between frequent eye movements (saccades)
      and short fixations in text. Yet, the impact of saccades on word processing
      remains unknown, as neuroimaging studies typically employ constant eye fixation.
      Here we investigate eye-movement effects on word recognition processes in healthy
      human subjects using anatomically constrained magnetoencephalography,
      psychophysical measurements, and saccade detection in real time. Word recognition
      was slower and brain responses were reduced to words presented early versus late
      after saccades, suggesting an overall transient impairment of word processing
      after eye movements. Response reductions occurred early in visual cortices and
      later in language regions, where they colocalized with repetition priming
      effects. Qualitatively similar effects occurred when words appeared early versus
      late after background movement that mimicked saccades, suggesting that retinal
      motion contributes to postsaccadic inhibition. Further, differences in
      postsaccadic and background-movement effects suggest that central mechanisms also
      contribute to postsaccadic modulation. Together, these results suggest a complex
      interplay between visual and central saccadic mechanisms during reading.

PMID- 22457497
TI  - Extent of bilateral neuronal network reorganization and functional recovery in
      relation to stroke severity.
AB  - Remodeling of neuronal structures and networks is believed to significantly
      contribute to (partial) restoration of functions after stroke. However, it has
      been unclear to what extent the brain reorganizes and how this correlates with
      functional recovery in relation to stroke severity. We applied serial resting
      state functional MRI and diffusion tensor imaging together with behavioral
      testing to relate longitudinal modifications in functional and structural
      connectivity of the sensorimotor neuronal network to changes in sensorimotor
      function after unilateral stroke in rats. We found that gradual improvement of
      functions is associated with wide-ranging changes in functional and structural
      connectivity within bilateral neuronal networks, particularly after large stroke.
      Both after medium and large stroke, brain reorganization eventually leads to
      (partial) normalization of neuronal signal synchronization within the affected
      sensorimotor cortical network (intraregional signal coherence), as well as
      between the affected and unaffected sensorimotor cortices (interhemispheric
      functional connectivity). Furthermore, the bilateral network configuration shifts
      from subacutely increased "small-worldness," possibly reflective of initial
      excessive neuronal clustering and wiring, toward a baseline small-world topology,
      optimal for global information transfer and local processing, at chronic stages.
      Cortical network remodeling was accompanied by recovery of initially disrupted
      structural integrity in corticospinal tract regions, which correlated positively
      with retrieval of sensorimotor functions. Our study demonstrates that the degree
      of functional recovery after stroke is associated with the extent of preservation
      or restoration of ipsilesional corticospinal tracts in combination with
      reinstatement of interhemispheric neuronal signal synchronization and
      normalization of small-world cortical network organization.

PMID- 22457498
TI  - Cortical dynamics of sensorimotor integration during grasp planning.
AB  - Our sensorimotor interactions with objects are guided by their current spatial
      and perceptual features, as well as by learned object knowledge. A fresh red
      tomato is grasped differently than a soft overripe tomato, even when those
      objects possess the same spatial metrics of size and shape. Objects' spatial and
      perceptual features need to be integrated during grasping, but those features are
      analyzed in two anatomically distinct neural pathways. The anterior intraparietal
      sulcus (aIPS) might support the integration of those features. We combine
      transcranial magnetic stimulation (TMS) interference, EEG recordings, and
      psychophysical methods to test aIPS causal contributions to sensorimotor
      integration, characterizing the dynamics of those contributions during motor
      planning. Human subjects performing grasping movements were provided with visual
      information about a target object, namely spatial and pictorial cues, whose
      availability and information value were independently modulated on each trial.
      Maximally informative visual cues, irrespective of their spatial or perceptual
      nature, led to enhanced motor preparatory activity early during movement
      planning, and to stronger spatial congruency between finger trajectories and
      target object. Disturbing aIPS activity with single-pulse TMS within 200 ms after
      object presentation reduced those electrophysiological and behavioral indices of
      enhanced motor planning. TMS interference with aIPS also disturbed subjects'
      ability to use learned object knowledge during motor planning. These results
      indicate that aIPS is necessary for the fast generation of a new motor plan on
      the basis of both spatial and pictorial cues. Furthermore, as learned object
      knowledge becomes available, aIPS comes to strongly depend on this prior
      information for structuring the motor plan.

PMID- 22457500
TI  - Early binding of gaze, gesture, and emotion: neural time course and correlates.
AB  - Communicative intentions are transmitted by many perceptual cues, including gaze
      direction, body gesture, and facial expressions. However, little is known about
      how these visual social cues are integrated over time in the brain and, notably,
      whether this binding occurs in the emotional or the motor system. By coupling
      magnetic resonance and electroencephalography imaging in humans, we were able to
      show that, 200 ms after stimulus onset, the premotor cortex integrated gaze,
      gesture, and emotion displayed by a congener. At earlier stages, emotional
      content was processed independently in the amygdala (170 ms), whereas directional
      cues (gaze direction with pointing gesture) were combined at ~190 ms in the
      parietal and supplementary motor cortices. These results demonstrate that the
      early binding of visual social signals displayed by an agent engaged the dorsal
      pathway and the premotor cortex, possibly to facilitate the preparation of an
      adaptive response to another person's immediate intention.

PMID- 22457499
TI  - Cholinergic induction of input-specific late-phase LTP via localized Ca2+ release
      in the visual cortex.
AB  - Acetylcholine facilitates long-term potentiation (LTP) and long-term depression
      (LTD), substrates of learning, memory, and sensory processing, in which
      acetylcholine also plays a crucial role. Ca(2+) ions serve as a canonical
      regulator of LTP/LTD but little is known about the effect of acetylcholine on
      intracellular Ca(2+) dynamics. Here, we investigated dendritic Ca(2+) dynamics
      evoked by synaptic stimulation and the resulting LTP/LTD in layer 2/3 pyramidal
      neurons of the rat visual cortex. Under muscarinic stimulation, single-shock
      electrical stimulation (SES) inducing ~20 mV EPSP, applied via a glass electrode
      located ~10 MUm from the basal dendrite, evoked NMDA receptor-dependent fast
      Ca(2+) transients and the subsequent Ca(2+) release from the inositol 1,4,5
      trisphosphate (IP(3))-sensitive stores. These secondary dendritic Ca(2+)
      transients were highly localized within 10 MUm from the center (SD = 5.0 MUm).
      The dendritic release of Ca(2+) was a prerequisite for input-specific muscarinic
      LTP (LTPm). Without the secondary Ca(2+) release, only muscarinic LTD (LTDm) was
      induced. D(-)-2-amino-5-phosphopentanoic acid and intracellular heparin blocked
      LTPm as well as dendritic Ca(2+) release. A single burst consisting of 3 EPSPs
      with weak stimulus intensities instead of the SES also induced secondary Ca(2+)
      release and LTPm. LTPm and LTDm were protein synthesis-dependent. Furthermore,
      LTPm was confined to specific dendritic compartments and not inducible in distal
      apical dendrites. Thus, cholinergic activation facilitated selectively
      compartment-specific induction of late-phase LTP through IP(3)-dependent Ca(2+)
      release.

PMID- 22457501
TI  - delta-opioid receptor function in the dorsal striatum plays a role in high levels
      of ethanol consumption in rats.
AB  - Binge-like patterns of excessive drinking during young adulthood increase the
      propensity for alcohol use disorders (AUDs) later in adult life; however, the
      mechanisms that drive this are not completely understood. Previous studies showed
      that the delta-opioid peptide receptor (DOP-R) is dynamically regulated by
      exposure to ethanol and that the DOP-R plays a role in ethanol-mediated
      behaviors. The aim of this study was to determine the role of the DOP-R in high
      ethanol consumption from young adulthood through to late adulthood by measuring
      DOP-R-mediated [(35)S]GTPgammaS binding in brain membranes and DOP-R-mediated
      analgesia using a rat model of high ethanol consumption in Long Evans rats. We
      show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia
      changes during development, being highest during early adulthood and reduced in
      late adulthood. Intermittent access to ethanol but not continuous ethanol or
      water from young adulthood leads to an increase in DOP-R activity in the dorsal
      striatum and DOP-R-mediated analgesia into late adulthood. Multiple
      microinfusions of naltrindole into the dorsal striatum or multiple systemic
      administration of naltrindole reduces ethanol consumption, and following
      termination of treatment, DOP-R activity in the dorsal striatum is attenuated.
      These findings suggest that DOP-R activity in the dorsal striatum plays a role in
      high levels of ethanol consumption and suggest that targeting the DOP-R is an
      alternative strategy for the treatment of AUDs.

PMID- 22457502
TI  - Interaction of BDNF and COMT polymorphisms on paired-associative stimulation
      induced cortical plasticity.
AB  - The common single-nucleotide polymorphism (SNP) brain-derived neurotrophic factor
      (BDNF) valine-to-methionine substitution at codon 66 (Val66Met) has been
      associated with differences in memory functions and cortical plasticity following
      brain stimulation. Other studies could not confirm these results, though, and
      potential interactions of BDNF carrier status with other learning-relevant SNPs
      are largely unknown. The present study aimed to evaluate the effects of BDNF
      Val66Met genotype on paired associative stimulation (PAS)-induced motor cortex
      plasticity, while additionally taking catechol-O-methyltransferase (COMT)
      Val158Met and kidney and brain (KIBRA) rs17070145 carrier status into account.
      Therefore, a cohort of 2 * 16 age- and education-matched healthy young females
      underwent transcranial magnetic stimulation using an excitatory PAS(25) protocol
      to induce cortical plasticity. Cognitive performance was assessed using implicit
      grammar- and motor-learning tasks and a detailed neuropsychological test battery.
      While BDNF carrier status alone did not significantly influence PAS-induced
      cortical plasticity, we found a significant BDNF * COMT interaction, showing
      higher plasticity immediately following the PAS(25) protocol for the BDNF Val/Val
      vs Met genotype in COMT Met homozygotes only (ANOVA, p = 0.027). A similar
      advantage for this group was noted for implicit grammar learning (ANOVA, p =
      0.021). Accounting for KIBRA rs17070145 did not explain significant variance. Our
      findings for the first time demonstrate an interaction of BDNF by COMT on human
      cortical plasticity. Moreover, they show that genotype-related differences in
      neurophysiology translate into behavioral differences. These findings might
      contribute to a better understanding of the mechanisms of interindividual
      differences in cognition.

PMID- 22457503
TI  - MAGE-D1 regulates expression of depression-like behavior through serotonin
      transporter ubiquitylation.
AB  - The ubiquitin-proteasome system (UPS) controls the stability of most cellular
      proteins. The polymorphism of UPS-related genes is associated with major
      depression disorder, but less is known about the molecule that plays a role in
      depression by modulating the UPS. Melanoma antigen gene-D1 (MAGE-D1) interacts
      with RING E3 ubiquitin ligase and is implicated in protein degradation. MAGE-D1
      may thus play an important role in the CNS via ubiquitylation. Here, we clarified
      a novel role of MAGE-D1 in emotional functions, namely its modulation of
      ubiquitylation to the serotonin transporter (SERT). The MAGE-D1 knock-out and
      knockdown by small interfering RNA (siRNA) in the prefrontal cortex showed
      depression-like behavior, such as a decrease in exploratory behavior in both the
      home cage and novel apparatus, a decrease in social interaction, increased
      immobility time during forced swimming and tail suspension, and a decrease in
      sucrose preference without any anxiety, or cognitive or motor dysfunction. Acute
      and chronic (28 d) administration of sertraline (10 mg/kg) and imipramine (20
      mg/kg) reversed all or part of depression-like behavior in knock-out mice. In
      these mice, the serotonergic function in the prefrontal cortex and hippocampus
      was hypoactive, accompanied by hyperexpression of SERT attributable to a decrease
      in ubiquitylation. Furthermore, MAGE-D1 binds to SERT via the necdin homology
      domain. MAGE-D1 overexpression in cells resulted in a decrease in serotonin
      uptake activity and the protein level of SERT but an increase in ubiquitylated
      SERT. Together, the present findings suggest a novel role for MAGE-D1 in
      depressive behaviors: modulating SERT ubiquitylation.

PMID- 22457504
TI  - Massed training-induced intermediate-term operant memory in aplysia requires
      protein synthesis and multiple persistent kinase cascades.
AB  - The Aplysia feeding system with its high degree of plasticity and well
      characterized neuronal circuitry is well suited for investigations of memory
      formation. We used an operant paradigm, learning that food is inedible (LFI), to
      investigate the signaling pathways underlying intermediate-term memory (ITM) in
      Aplysia. During a single massed training session, the animal associates a
      specific seaweed with the failure to swallow, generating short-term (30 min) and
      long-term (24 h) memory. We investigated whether the same training protocol
      induced the formation of ITM. We found that massed LFI training resulted in
      temporally distinct protein synthesis-dependent memory evident 4-6 h after
      training. Through in vivo experiments, we determined that the formation of ITM
      required protein kinase A, protein kinase C, and MAPK. Moreover, the maintenance
      of ITM required PKA, PKM Apl III, and MAPK because inhibition of any of these
      kinases after training or before testing blocked the expression of memory. In
      contrast, additional experiments determined that the maintenance of long-term
      memory appeared independent of PKM Apl III. Using Western blotting, we found that
      sustained MAPK phosphorylation was dependent upon protein synthesis, but not PKA
      or PKC activity. Thus, massed training-induced intermediate-term operant memory
      requires protein synthesis as well as persistent or sustained kinase signaling
      for PKA, PKC, and MAPK. While short-, intermediate-, and long-term memory are
      induced by the same training protocol, considerable differences exist in both the
      combination and timing of signaling cascades that induce the formation and
      maintenance of these temporally distinct memories.

PMID- 22457505
TI  - Push-pull control of motor output.
AB  - Inhibition usually decreases input-output excitability of neurons. If, however,
      inhibition is coupled to excitation in a push-pull fashion, where inhibition
      decreases as excitation increases, neuron excitability can be increased. Although
      the presence of push-pull organization has been demonstrated in single cells, its
      functional impact on neural processing depends on its effect on the system level.
      We studied push-pull in the motor output stage of the feline spinal cord, a
      system that allows independent control of inhibitory and excitatory components.
      Push-pull organization was clearly present in ankle extensor motoneurons,
      producing increased peak-to-peak modulation of synaptic currents. The effect at
      the system level was equally strong. Independent control of the inhibitory
      component showed that the stronger the background of inhibition, the greater the
      peak force production. This illustrates the paradox at the heart of push-pull
      organization: increased force output can be achieved by increasing background
      inhibition to provide greater disinhibition.

PMID- 22457506
TI  - Large membrane domains in hair bundles specify spatially constricted radixin
      activation.
AB  - The plasma membrane of vertebrate hair bundles interacts intimately with the
      bundle cytoskeleton to support mechanotransduction and homeostasis. To determine
      the membrane composition of bundles, we used lipid mass spectrometry with
      purified chick vestibular bundles. While the bundle glycerophospholipids and acyl
      chains resemble those of other endomembranes, bundle ceramide and sphingomyelin
      nearly exclusively contain short-chain, saturated acyl chains. Confocal imaging
      of isolated bullfrog vestibular hair cells shows that the bundle membrane
      segregates spatially into at least three large structural and functional domains.
      One membrane domain, including the stereocilia basal tapers and ~1 MUm of the
      shaft, the location of the ankle links, is enriched in the lipid phosphatase
      PTPRQ (protein tyrosine phosphatase Q) and polysialylated gangliosides. The taper
      domain forms a sharp boundary with the shaft domain, which contains the plasma
      membrane Ca(2+)-ATPase isoform 2 (PMCA2) and phosphatidylinositol 4,5
      bisphosphate [PI(4,5)P(2)]; moreover, a tip domain has elevated levels of
      cholesterol, PMCA2, and PI(4,5)P(2). Protein mass spectrometry shows that bundles
      from chick vestibular hair cells contain a complete set of proteins that
      transport, synthesize, and degrade PI(4,5)P(2). The membrane domains have
      functional significance; radixin, essential for hair-bundle stability, is
      activated at the taper-shaft boundary in a PI(4,5)P(2)-dependent manner, allowing
      assembly of protein complexes at that site. Membrane domains within stereocilia
      thus define regions within hair bundles that allow compartmentalization of Ca(2+)
      extrusion and assembly of protein complexes at discrete locations.

PMID- 22457507
TI  - Excitotoxicity downregulates TrkB.FL signaling and upregulates the
      neuroprotective truncated TrkB receptors in cultured hippocampal and striatal
      neurons.
AB  - Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal
      survival through activation of TrkB receptors. The trkB gene encodes a full
      length receptor tyrosine kinase (TrkB.FL) and its truncated (T1/T2) isoforms. We
      investigated the changes in TrkB protein levels and signaling activity under
      excitotoxic conditions, which are characteristic of brain ischemia, traumatic
      brain injury, and neurodegenerative disorders. Excitotoxic stimulation of
      cultured rat hippocampal or striatal neurons downregulated TrkB.FL and
      upregulated a truncated form of the receptor (TrkB.T). Downregulation of TrkB.FL
      was mediated by calpains, whereas the increase in TrkB.T protein levels required
      transcription and translation activities. Downregulation of TrkB.FL receptors in
      hippocampal neurons correlated with a decrease in BDNF-induced activation of the
      Ras/ERK and PLCgamma pathways. However, calpain inhibition, which prevents
      TrkB.FL degradation, did not preclude the decrease in signaling activity of these
      receptors. On the other hand, incubation with anisomycin, to prevent the
      upregulation of TrkB.T, protected to a large extent the TrkB.FL signaling
      activity, suggesting that truncated receptors may act as dominant-negatives. The
      upregulation of TrkB.T under excitotoxic conditions was correlated with an
      increase in BDNF-induced inhibition of RhoA, a mediator of excitotoxic neuronal
      death. BDNF fully protected hippocampal neurons transduced with TrkB.T when
      present during excitotoxic stimulation with glutamate, in contrast with the
      partial protection observed in cells overexpressing TrkB.FL or expressing GFP.
      These results indicate that BDNF protects hippocampal neurons by two distinct
      mechanisms: through the neurotrophic effects of TrkB.FL receptors and by
      activation of TrkB.T receptors coupled to inhibition of the excitotoxic
      signaling.

PMID- 22457509
TI  - Mixed inhibitory synaptic balance correlates with glutamatergic synaptic
      phenotype in cerebellar unipolar brush cells.
AB  - Inhibitory synapses display a great diversity through varying combinations of
      presynaptic GABA and glycine release and postsynaptic expression of GABA and
      glycine receptor subtypes. We hypothesized that increased flexibility offered by
      this dual transmitter system might serve to tune the inhibitory phenotype to the
      properties of afferent excitatory synaptic inputs in individual cells.
      Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic
      synapse from a mossy fiber (MF), which makes them an ideal model to study
      excitatory-inhibitory interactions. We examined the functional phenotypes of
      mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices.
      We show that glycinergic IPSCs are present in all cells. An additional GABAergic
      component of large amplitude is only detected in a subpopulation of UBCs. This
      GABAergic phenotype is strictly anti-correlated with the expression of type II,
      but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse.
      Immunohistochemical stainings and agonist applications show that global UBC
      expression of glycine and GABA(A) receptors matches the pharmacological profile
      of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic
      origin of the inhibitory phenotype, including the slow kinetics of glycinergic
      components. These results strongly suggest the presence of a functional
      coregulation of excitatory and inhibitory phenotypes at the single-cell level. We
      propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the
      gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in
      addition control spike timing in mGluRII-negative UBCs.

PMID- 22457508
TI  - A septal-hypothalamic pathway drives orexin neurons, which is necessary for
      conditioned cocaine preference.
AB  - Orexins (also called hypocretins) have been shown to be importantly involved in
      reward and addiction, but little is known about the circuitry that regulates
      orexin neuronal activity during drug-seeking behaviors. Here, we examined inputs
      to the lateral hypothalamus (LH) orexin cell field from the lateral septum (LS)
      using tract-tracing and Fos immunohistochemistry after cocaine (10 mg/kg)
      conditioned place preference (CPP) in Sprague Dawley rats. We found that neurons
      in rostral LS (LSr) that project to LH are Fos-activated in proportion to cocaine
      CPP, and that inhibition of LSr neurons with local baclofen and muscimol
      microinjection (0.3/0.03 nmol) blocks expression of Fos in LH orexin cells and
      cocaine preference. In addition, using local inactivation in LS and orexin
      antisense morpholinos in LH, we found that LSr influences on LH orexin neurons
      are critical for the expression of cocaine preference. These results indicate
      that LSr activates LH orexin neurons during cocaine place preference, and that
      this circuit is essential for expression of cocaine place preference.

PMID- 22457510
TI  - Differential roles of the dorsolateral and midlateral striatum in punished
      cocaine seeking.
AB  - Continued instrumental drug seeking despite contingent punishment is a core
      phenotype of drug addiction. Although the neuroanatomical basis of punished drug
      seeking is unclear, we hypothesize that the sensorimotor striatum, a structure
      that mediates habitual drug seeking, also mediates punished cocaine seeking.
      Forelimb sensorimotor projections into the striatum of the rat extend from the
      dorsolateral to midlateral striatum. Here, we selectively inactivated the
      dorsolateral and midlateral striatum in rats responding for cocaine in a seeking
      taking task. We inactivated both regions after the acquisition of cocaine
      seeking, after extended cocaine self-administration and finally after the
      introduction of intermittent, seeking-contingent foot shock. The results show
      that inactivation of the dorsolateral striatum selectively disrupted punished
      drug seeking but did not affect unpunished drug seeking, even after extended
      training. Inactivation of the midlateral striatum, on the other hand, disrupted
      drug seeking at all stages of training. The effect of inactivating the
      dorsolateral striatum under punishment conditions was present before delivery of
      the first shock in the session, and responding reverted to baseline the next day.
      Thus, inactivation of the dorsolateral striatum seems to enhance the influence of
      recalled threat of negative consequences of cocaine seeking. The proportional
      reduction in responding after inactivation of the dorsolateral striatum did not
      vary with the individual level of compulsivity. Together, these results suggest a
      novel differentiation of function in the sensorimotor striatum, where the
      dorsolateral striatum selectively mediates the rigidity of responding after
      overtraining, while the midlateral striatum mediates responding itself at all
      stages of training.

PMID- 22457511
TI  - Epigenetic modulation of Homer1a transcription regulation in amygdala and
      hippocampus with pavlovian fear conditioning.
AB  - The consolidation of conditioned fear involves upregulation of genes necessary
      for long-term memory formation. An important question remains as to whether this
      results in part from epigenetic regulation and chromatin modulation. We examined
      whether Homer1a, which is required for memory formation, is necessary for
      Pavlovian cued fear conditioning, whether it is downstream of BDNF-TrkB
      activation, and whether this pathway utilizes histone modifications for activity
      dependent transcriptional regulation. We initially found that Homer1a knock-out
      mice exhibited deficits in cued fear conditioning (5 tone-shock presentations
      with 70 dB, 6 kHz tones and 0.5 s, 0.6 mA footshocks). We then demonstrated that:
      (1) Homer1a mRNA increases after fear conditioning in vivo within both amygdala
      and hippocampus of wild-type mice; (2) it increases after BDNF application to
      primary hippocampal and amygdala cultures in vitro; and (3) these increases are
      dependent on transcription and MAPK signaling. Furthermore, using chromatin
      immunoprecipitation we found that both in vitro and in vivo manipulations result
      in decreases in Homer1 promoter H3K9 methylation in amygdala cells but increases
      in Homer1 promoter H3 acetylation in hippocampal cells. However, no changes were
      observed in H4 acetylation or H3K27 dimethylation. Inhibition of histone
      deacetylation by sodium butyrate enhanced contextual but not cued fear
      conditioning and enhanced Homer1 H3 acetylation in the hippocampus. These data
      provide evidence for dynamic epigenetic regulation of Homer1a following BDNF
      induced plasticity and during a BDNF-dependent learning process. Furthermore,
      upregulation of this gene may be regulated through distinct epigenetic
      modifications in the hippocampus and amygdala.

PMID- 22457512
TI  - Global not local masker features govern the auditory continuity illusion.
AB  - When an acoustic signal is temporarily interrupted by another sound, it is
      sometimes heard as continuing through, even when the signal is actually turned
      off during the interruption-an effect known as the "auditory continuity
      illusion." A widespread view is that the illusion can only occur when peripheral
      neural responses contain no evidence that the signal was interrupted. Here we
      challenge this view using a combination of psychophysical measures from human
      listeners and computational simulations with a model of the auditory periphery.
      The results reveal that the illusion seems to depend more on the overall specific
      loudness than on the peripheral masking properties of the interrupting sound.
      This finding indicates that the continuity illusion is determined by the global
      features, rather than the fine-grained temporal structure, of the interrupting
      sound, and argues against the view that the illusion arises in the auditory
      periphery.

PMID- 22457513
TI  - A Drosophila DEG/ENaC subunit functions specifically in gustatory neurons
      required for male courtship behavior.
AB  - Detection of specific female pheromones stimulates courtship behavior in
      Drosophila melanogaster males, but the chemosensory molecules, cells, and
      mechanisms involved remain poorly understood. Here we show that ppk25, a DEG/ENaC
      ion channel subunit required for normal male response to females, is expressed at
      highest levels in a single sexually dimorphic gustatory neuron of most taste
      hairs on legs and wings, but not in neurons that detect courtship-inhibiting
      pheromones or food. Synaptic inactivation of ppk25-expressing neurons, or
      knockdown of ppk25 expression in all gustatory neurons, significantly impairs
      male response to females, whereas gustatory expression of ppk25 rescues the
      courtship behavior of ppk25 mutant males. Remarkably, the only other detectable
      albeit significantly weaker expression of ppk25 occurs in olfactory neurons
      implicated in modulation of courtship behavior. However, expression of ppk25 in
      olfactory neurons is not required for male courtship under our experimental
      conditions. These data show that ppk25 functions specifically in peripheral taste
      neurons involved in activation of courtship behavior, an unexpected function for
      this type of channel. Furthermore, our work identifies a small subset of
      gustatory neurons with an essential role in activation of male courtship
      behavior, most likely in response to female pheromones.

PMID- 22457515
TI  - GluRdelta2 assembles four neurexins into trans-synaptic triad to trigger synapse
      formation.
AB  - Elucidation of molecular mechanisms of synapse formation is a prerequisite for
      the understanding of neural wiring, higher brain functions, and mental disorders.
      The trans-synaptic interaction of postsynaptic glutamate receptor delta2
      (GluRdelta2) and presynaptic neurexins (NRXNs) through cerebellin precursor
      protein 1 (Cbln1) mediates synapse formation in vivo in the cerebellum. Here, we
      asked how the trans-synaptic triad induces synapse formation. Native GluRdelta2
      existed as a tetramer in the membrane, whereas the N-terminal domain (NTD) of
      GluRdelta2 formed a stable homodimer. When incubated with cultured mouse
      cerebellar granule cells (GCs), dimeric GluRdelta2-NTD and Cbln1 exerted little
      effect on the accumulation of punctate immunostaining signals for Bassoon and
      vesicular glutamate transporter 1 in GC axons. However, tetramerized GluRdelta2
      NTD stimulated the accumulation of these presynaptic proteins in the axons.
      Analysis of Cbln1 mutants suggested that the binding sites of GluRdelta2 and
      NRXN1beta on Cbln1 are differential. Furthermore, there was no competition in the
      binding to Cbln1 between GluRdelta2-NTD and the extracellular domain (ECD) of
      NRXN1beta. Thus, GluRdelta2 and Cbln1 interacted with each other rather
      independently of Cbln1-NRXN1beta interaction and vice versa. Gel filtration and
      isothermal titration calorimetry analyses consistently showed that dimeric
      GluRdelta2-NTD and hexameric Cbln1 assembled in the 1:1 ratio, whereas hexameric
      Cbln1 and the laminin-neurexin-sex hormone-binding globulin domain of NRXN1beta
      ECD assembled in the 1:2 ratio. Thus, the synaptogenic triad is assembled from
      tetrameric GluRdelta2, hexameric Cbln1, and monomeric NRXN in the ratio of 1:2:4.
      These results suggest that GluRdelta2 triggers synapse formation by clustering
      four NRXNs through triad formation.

PMID- 22457514
TI  - Photoreceptor coupling mediated by connexin36 in the primate retina.
AB  - Photoreceptors are coupled via gap junctions in many mammalian species. Cone-to
      cone coupling is thought to improve sensitivity and signal-to-noise ratio, while
      rod-to-cone coupling provides an alternative rod pathway active under twilight or
      mesopic conditions (Smith et al., 1986; DeVries et al., 2002; Hornstein et al.,
      2005). Gap junctions are composed of connexins, and connexin36 (Cx36), the
      dominant neuronal connexin, is expressed in the outer plexiform layer. Primate
      (Macaca mulatta) cone pedicles, labeled with an antibody against cone arrestin
      (7G6) were connected by a network of fine processes called telodendria and, in
      double-labeled material, Cx36 plaques were located precisely at telodendrial
      contacts between cones, suggesting strongly they are Cx36 gap junctions. Each
      red/green cone made nonselective connections with neighboring red/green cones. In
      contrast, blue cone pedicles were smaller with relatively few short telodendria
      and they made only rare or equivocal Cx36 contacts with adjacent cones. There
      were also many smaller Cx36 plaques around the periphery of every cone pedicle
      and along a series of very fine telodendria that were too short to reach adjacent
      members of the cone pedicle mosaic. These small Cx36 plaques were closely aligned
      with nearly every rod spherule and may identify sites of rod-to-cone coupling,
      even though the identity of the rod connexin has not been established. We
      conclude that the matrix of cone telodendria is the substrate for photoreceptor
      coupling. Red/green cones were coupled indiscriminately but blue cones were
      rarely connected with other cones. All cone types, including blue cones, made gap
      junctions with surrounding rod spherules.

PMID- 22457516
TI  - Food intake in lean and obese mice after peripheral administration of glucagon
      like peptide 2.
AB  - We investigated the potential anorectic action of peripherally administered
      glucagon-like peptide 2 (GLP2) in lean and diet-induced obese (DIO) mice. Mice,
      fasted for 16 h, were injected i.p. with native GLP2 or [Gly2]GLP2, stable analog
      of GLP2, before or after GLP2 (3-33), a GLP2 receptor (GLP2R) antagonist, or
      exendin (9-39), a GLP1R antagonist. Food intake was measured at intervals 1, 2,
      4, 8, and 24 h postinjection. In addition, we tested in lean mice the influence
      of [Gly2]GLP2 on gastric emptying and the effects of GLP1 alone or in combination
      with [Gly2]GLP2 on food intake. [Gly2]GLP2 dose dependently and significantly
      inhibited food intake in lean and DIO mice. The reduction of food intake occurred
      in the first hour postinjection and it was sustained until 4 h postinjection in
      lean mice while it was sustained until 2 h postinjection in DIO mice. GLP2
      significantly inhibited food intake in both lean and DIO mice but only in the
      first hour postinjection. The efficiency of [Gly2]GLP2 or GLP2 in suppressing
      food intake was significantly weaker in DIO mice compared with lean animals. The
      [Gly2]GLP2 anorectic actions were blocked by the GLP2R antagonist GLP2 (3-33) or
      by the GLP1R antagonist exendin (9-39). The coadministration of [Gly2]GLP2 and
      GLP1 did not cause additive effects. [Gly2]GLP2 decreased the gastric emptying
      rate. Results suggest that GLP2 can reduce food intake in mice in the short term,
      likely acting at a peripheral level. DIO mice are less sensitive to the anorectic
      effect of the peptide.

PMID- 22457518
TI  - Reconstruction of human papillomavirus type 16-mediated early-stage neoplasia
      implicates E6/E7 deregulation and the loss of contact inhibition in neoplastic
      progression.
AB  - Infection with human papillomavirus type 16 (HPV-16) can lead to low- or high
      grade squamous intraepithelial lesions (LSIL or HSIL). Here we show that these in
      vivo disease states can be replicated in raft cultures of early-pass HPV-16
      episomal cell lines, at both the level of pathology and the level of viral gene
      expression. A reduced responsiveness to cell-cell contact inhibition and an
      increase in E6/E7 activity correlated closely with phenotype. Similar
      deregulation is likely to underlie the appearance of LSIL or HSIL soon after
      infection.

PMID- 22457517
TI  - Role of beta-adrenergic receptors in regulation of hepatic fat accumulation
      during aging.
AB  - Excessive fat accumulation in liver (hepatic steatosis) predisposes to hepatic
      functional and structural impairment and overall metabolic risk. Previous studies
      noted an association between hepatic steatosis and age in humans and rodents.
      However, the mechanisms leading to age-associated hepatic fat accumulation remain
      unknown. Earlier work from our group showed that beta-adrenergic receptor (beta
      AR) levels and beta-AR-stimulated adenylyl cyclase activity increase in rat liver
      during aging. Here we investigated whether age-associated increases in beta-AR
      signaling play a role in augmenting hepatic lipid accumulation. We demonstrate an
      increase in hepatic lipid content during senescence and a significant correlation
      between hepatic fat content and stimulation of adenylyl cyclase activity by the
      beta-AR agonist isoproterenol in rat liver. Isoproterenol administration to young
      and old rodents in vivo increased hepatic lipid accumulation. Furthermore, in
      vitro overexpression of beta1- and beta2-AR subtypes in hepatocytes from young
      rodents increased cellular lipid content, whereas inhibition of beta-ARs by
      receptor subtype-specific inhibitors reduced lipid levels in hepatocytes from
      senescent animals. Isoproterenol-induced hepatic lipid accumulation in vivo was
      prevented by the beta-AR nonselective blocker propranolol, suggesting a novel
      therapeutic effect of this class of drugs in hepatic steatosis. Acipimox, which
      inhibits adipose tissue lipolysis, did not alter isoproterenol-mediated hepatic
      fat accumulation; thus beta-AR responsive hepatic lipid accumulation does not
      appear to be related primarily to altered lipolysis. These findings suggest that
      augmented hepatic beta-AR signaling during aging may increase lipid accumulation
      in liver and advocate a possible role for beta-adrenergic blockers in preventing
      or retarding the development of hepatic steatosis.

PMID- 22457519
TI  - Attenuation of Chikungunya virus vaccine strain 181/clone 25 is determined by two
      amino acid substitutions in the E2 envelope glycoprotein.
AB  - Chikungunya virus (CHIKV) is the mosquito-borne alphavirus that is the etiologic
      agent of massive outbreaks of arthralgic febrile illness that recently affected
      millions of people in Africa and Asia. The only CHIKV vaccine that has been
      tested in humans, strain 181/clone 25, is a live-attenuated derivative of
      Southeast Asian human isolate strain AF15561. The vaccine was immunogenic in
      phase I and II clinical trials; however, it induced transient arthralgia in 8% of
      the vaccinees. There are five amino acid differences between the vaccine and its
      parent, as well as five synonymous mutations, none of which involves cis-acting
      genome regions known to be responsible for replication or packaging. To identify
      the determinants of attenuation, we therefore tested the five nonsynonymous
      mutations by cloning them individually or in different combinations into
      infectious clones derived from two wild-type (WT) CHIKV strains, La Reunion and
      AF15561. Levels of virulence were compared with those of the WT strains and the
      vaccine strain in two different murine models: infant CD1 and adult A129 mice. An
      attenuated phenotype indistinguishable from that of the 181/clone 25 vaccine
      strain was obtained by the simultaneous expression of two E2 glycoprotein
      substitutions, with intermediate levels of attenuation obtained with the single
      E2 mutations. The other three amino acid mutations, in nsP1, 6K, and E1, did not
      have a detectable effect on CHIKV virulence. These results indicate that the
      attenuation of strain 181/clone 25 is mediated by two point mutations, explaining
      the phenotypic instability observed in human vaccinees and also in our studies.

PMID- 22457520
TI  - Human monoclonal antibodies to pandemic 1957 H2N2 and pandemic 1968 H3N2
      influenza viruses.
AB  - Investigation of the human antibody response to the 1957 pandemic H2N2 influenza
      A virus has been largely limited to serologic studies. We generated five
      influenza virus hemagglutinin (HA)-reactive human monoclonal antibodies (MAbs) by
      hybridoma technology from the peripheral blood of healthy donors who were born
      between 1950 and 1968. Two MAbs reacted with the pandemic H2N2 virus, two
      recognized the pandemic H3N2 virus, and remarkably, one reacted with both the
      pandemic H2N2 and H3N2 viruses. Each of these five naturally occurring MAbs
      displayed hemagglutination inhibition activity, suggesting specificity for the
      globular head domain of influenza virus HA. When incubated with virus, MAbs 8F8,
      8M2, and 2G1 each elicited H2N2 escape mutations immediately adjacent to the
      receptor-binding domain on the HA globular head in embryonated chicken eggs. All
      H2N2-specific MAbs were able to inhibit a 2006 swine H2N3 influenza virus. MAbs
      8M2 and 2G1 shared the V(H)1-69 germ line gene, but these antibodies were
      otherwise not genetically related. Each antibody was able to protect mice in a
      lethal H2N2 virus challenge. Thus, even 43 years after circulation of H2N2
      viruses, these subjects possessed peripheral blood B cells encoding potent
      inhibiting antibodies specific for a conserved region on the globular head of the
      pandemic H2 HA.

PMID- 22457521
TI  - Identical consensus sequence and conserved genomic polymorphism of hepatitis E
      virus during controlled interspecies transmission.
AB  - High-throughput sequencing of bile and feces from two pigs experimentally
      infected with human hepatitis E virus (HEV) of genotype 3f revealed the same full
      length consensus sequence as in the human sample. Twenty-nine percent of
      polymorphic sites found in HEV from the human sample were conserved throughout
      the infection of the heterologous host. The interspecies transmission of HEV
      quasispecies is the result of a genomic negative-selection pressure on random
      mutations which can be deleterious to the viral population. HEV intrahost
      nucleotide diversity was found to be in the lower range of other human RNA
      viruses but correlated with values found for zoonotic viruses. HEV transmission
      between humans and pigs does not seem to be modulated by host-specific mutations,
      suggesting that adaptation is mainly regulated by ecological drivers.

PMID- 22457522
TI  - Deep sequencing reveals minor protease resistance mutations in patients failing a
      protease inhibitor regimen.
AB  - Standard genotypic antiretroviral resistance testing, performed by bulk
      sequencing, does not readily detect variants that comprise <20% of the
      circulating HIV-1 RNA population. Nevertheless, it is valuable in selecting an
      antiretroviral regimen after antiretroviral failure. In patients with poor
      adherence, resistant variants may not reach this threshold. Therefore, deep
      sequencing would be potentially valuable for detecting minority resistant
      variants. We compared bulk sequencing and deep sequencing to detect HIV-1 drug
      resistance at the time of a second-line protease inhibitor (PI)-based
      antiretroviral regimen failure. Eligibility criteria were virologic failure (HIV
      1 RNA load of >500 copies/ml) of a first-line nonnucleoside reverse transcriptase
      inhibitor-based regimen, with at least the M184V mutation (lamivudine
      resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based
      regimen. An amplicon-sequencing approach on the Roche 454 system was used. Six
      patients with viral loads of >90,000 copies/ml and one patient with a viral load
      of 520 copies/ml were included. Mutations not detectable by bulk sequencing
      during first- and second-line failure were detected by deep sequencing during
      second-line failure. Low-frequency variants (>0.5% of the sequence population)
      harboring major protease inhibitor resistance mutations were found in 5 of 7
      patients despite poor adherence to the LPV/r-based regimen. In patients with
      intermittent adherence to a boosted PI regimen, deep sequencing may detect
      minority PI-resistant variants, which likely represent early events in resistance
      selection. In patients with poor or intermittent adherence, there may be low
      evolutionary impetus for such variants to reach fixation, explaining the low
      prevalence of PI resistance.

PMID- 22457523
TI  - Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1
      function for insulin resistance.
AB  - Hepatitis C virus (HCV) infection significantly increases the prevalence of type
      2 diabetes mellitus (T2DM). Insulin receptor substrate 1 (IRS-1) plays a key role
      in insulin signaling, thus enabling metabolic regulation in mammalian cells. We
      have previously shown that HCV infection modulates phosphorylation of Akt, a
      downstream target of IRS-1. In this study, we further examined the status of
      total IRS-1 and the downstream regulation of the Akt pathway in understanding
      mTOR/S6K1 signaling using HCV genotype 2a (clone JFH1)-infected hepatocytes.
      Inhibition of IRS-1 expression was observed in HCV-infected hepatocytes compared
      to that in a mock-infected control. The status of the tuberous sclerosis complex
      (TSC-1/TSC-2) was significantly decreased after HCV infection of human
      hepatocytes, showing a modulation of the downstream Akt pathway. Subsequent study
      indicated an increased level of Rheb and mTOR expression in HCV-infected
      hepatocytes. Interestingly, the phosphoS6K1 level was higher in HCV-infected
      hepatocytes, suggesting a novel mechanism for IRS-1 inhibition. Ectopic
      expression of TSC-1/TSC-2 significantly recovered the IRS-1 protein expression
      level in HCV-infected hepatocytes. Further analyses indicated that HCV core
      protein plays a significant role in modulating the mTOR/S6K1 signaling pathway.
      Proteasome inhibitor MG 132 recovered IRS-1 and TSC1/2 expression, suggesting
      that degradation occurred via the ubiquitin proteasome pathway. A functional
      consequence of IRS-1 inhibition was reflected in a decrease in GLUT4 protein
      expression and upregulation of the gluconeogenic enzyme PCK2 in HCV-infected
      hepatocytes. Together, these observations suggested that HCV infection activates
      the mTOR/S6K1 pathway in inhibiting IRS-1 function and perturbs glucose
      metabolism via downregulation of GLUT4 and upregulation of PCK2 for insulin
      resistance.

PMID- 22457524
TI  - The Epstein-Barr virus BcRF1 gene product is a TBP-like protein with an essential
      role in late gene expression.
AB  - That the expression of late genes is coupled to viral genome replication is well
      established for all herpesviruses, but the exact mechanisms of their regulation,
      especially by viral proteins, are poorly understood. Here, we report the
      identification of the Epstein-Barr virus (EBV) early protein BcRF1 as a viral
      factor crucial for the activation of late gene transcription following viral DNA
      replication during the productive cycle. In order to study the function of the
      BcRF1 protein, we constructed a recombinant EBV lacking this gene. In HEK293
      cells, this recombinant virus underwent normal DNA replication during the
      productive cycle but failed to express high levels of late gene transcripts or
      proteins, resulting in a nonproductive infection. Interestingly, a TATT motif is
      present in the promoter of most EBV late genes, at the position of the TATA box.
      We show here that BcRF1 forms a complex with the TATT motif and that this
      interaction is required for activation of late viral gene expression. Moreover,
      our results suggest that BcRF1 acts via interaction with other viral proteins.

PMID- 22457525
TI  - Mus spicilegus endogenous retrovirus HEMV uses murine sodium-dependent myo
      inositol transporter 1 as a receptor.
AB  - We sought to determine the relationship between two recent additions to the
      murine leukemia virus (MLV) ecotropic subgroup: Mus cervicolor isolate M813 and
      Mus spicilegus endogenous retrovirus HEMV. Though divergent in sequence, the two
      viruses share an Env protein with similarly curtailed VRA and VRB regions, and
      infection by both is restricted to mouse cells. HEMV and M813 displayed
      reciprocal receptor interference, suggesting that they share a receptor.
      Expression of the M813 receptor murine sodium-dependent myo-inositol transporter
      1 (mSMIT1) allowed previously nonpermissive cells to be infected by HEMV,
      indicating that mSMIT1 also serves as a receptor for HEMV. Our findings add HEMV
      as a second member to the MLV subgroup that uses mSMIT1 to gain entry into cells.

PMID- 22457526
TI  - A new human DSG2-transgenic mouse model for studying the tropism and pathology of
      human adenoviruses.
AB  - We have recently reported that a group of human adenoviruses (HAdVs) uses
      desmoglein 2 (DSG2) as a receptor for infection. Among these are the widely
      distributed serotypes HAdV-B3 and HAdV-B7, as well as a newly emerged strain
      derived from HAdV-B14. These serotypes do not infect rodent cells and could not
      up until now be studied in small-animal models. We therefore generated transgenic
      mice containing the human DSG2 locus. These mice expressed human DSG2 (hDSG2) at
      a level and in a pattern similar to those found for humans and nonhuman primates.
      As an initial application of hDSG2-transgenic mice, we used a green fluorescent
      protein (GFP)-expressing HAdV-B3 vector (Ad3-GFP) and studied GFP transgene
      expression by quantitative reverse transcription-PCR (qRT-PCR) and
      immunohistochemistry subsequent to intranasal and intravenous virus application.
      After intranasal application, we found efficient transduction of bronchial and
      alveolar epithelial cells in hDSG2-transgenic mice. Intravenous Ad3-GFP injection
      into hDSG2-transgenic mice resulted in hDSG2-dependent transduction of epithelial
      cells in the intestinal and colon mucosa. Our findings give an explanation for
      clinical symptoms associated with infection by DSG2-interacting HAdVs and provide
      a rationale for using Ad3-derived vectors in gene therapy.

PMID- 22457527
TI  - A nonfucosylated variant of the anti-HIV-1 monoclonal antibody b12 has enhanced
      FcgammaRIIIa-mediated antiviral activity in vitro but does not improve protection
      against mucosal SHIV challenge in macaques.
AB  - Eliciting neutralizing antibodies is thought to be a key activity of a vaccine
      against human immunodeficiency virus (HIV). However, a number of studies have
      suggested that in addition to neutralization, interaction of IgG with Fc gamma
      receptors (FcgammaR) may play an important role in antibody-mediated protection.
      We have previously obtained evidence that the protective activity of the broadly
      neutralizing human IgG1 anti-HIV monoclonal antibody (MAb) b12 in macaques is
      diminished in the absence of FcgammaR binding capacity. To investigate antibody
      dependent cellular cytotoxicity (ADCC) as a contributor to FcgammaR-associated
      protection, we developed a nonfucosylated variant of b12 (NFb12). We showed that,
      compared to fully fucosylated (referred to as wild-type in the text) b12, NFb12
      had higher affinity for human and rhesus macaque FcgammaRIIIa and was more
      efficient in inhibiting viral replication and more effective in killing HIV
      infected cells in an ADCC assay. Despite these more potent in vitro antiviral
      activities, NFb12 did not enhance protection in vivo against repeated low-dose
      vaginal challenge in the simian-human immunodeficiency virus (SHIV)/macaque model
      compared to wild-type b12. No difference in protection, viral load, or infection
      susceptibility was observed between animals given NFb12 and those given fully
      fucosylated b12, indicating that FcgammaR-mediated activities distinct from
      FcgammaRIIIa-mediated ADCC may be important in the observed protection against
      SHIV challenge.

PMID- 22457528
TI  - Ultrastructural visualization of individual tegument protein dissociation during
      entry of herpes simplex virus 1 into human and rat dorsal root ganglion neurons.
AB  - Herpes simplex virus 1 (HSV-1) enters neurons primarily by fusion of the viral
      envelope with the host cell plasma membrane, leading to the release of the capsid
      into the cytosol. The capsid travels via microtubule-mediated retrograde
      transport to the nuclear membrane, where the viral DNA is released for
      replication in the nucleus. In the present study, the composition and kinetics of
      incoming HSV-1 capsids during entry and retrograde transport in axons of human
      fetal and dissociated rat dorsal root ganglia (DRG) neurons were examined by wide
      field deconvolution microscopy and transmission immunoelectron microscopy (TIEM).
      We show that HSV-1 tegument proteins, including VP16, VP22, most pUL37, and some
      pUL36, dissociated from the incoming virions. The inner tegument proteins,
      including pUL36 and some pUL37, remained associated with the capsid during virus
      entry and transit to the nucleus in the neuronal cell body. By TIEM, a
      progressive loss of tegument proteins, including VP16, VP22, most pUL37, and some
      pUL36, was observed, with most of the tegument dissociating at the plasma
      membrane of the axons and the neuronal cell body. Further dissociation occurred
      within the axons and the cytosol as the capsids moved to the nucleus, resulting
      in the release of free tegument proteins, especially VP16, VP22, pUL37, and some
      pUL36, into the cytosol. This study elucidates ultrastructurally the composition
      of HSV-1 capsids that encounter the microtubules in the core of human axons and
      the complement of free tegument proteins released into the cytosol during virus
      entry.

PMID- 22457530
TI  - Full genomic sequence of the prototype strain (M64) of Rio Bravo virus.
AB  - Rio Bravo virus (RBV) is a member of the family Flaviviridae, genus Flavivirus.
      It belongs to a group of viruses in the genus with no known vector. In this
      report, we analyze the complete genome of the prototype RBV, strain M64.

PMID- 22457529
TI  - APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus
      type 1.
AB  - The human APOBEC3 family consists of seven cytidine deaminases (A3A to A3H), some
      of which display potent antiretroviral activity against HIV-1 and other
      retroviruses. Studies that analyzed the effect of A3G on human T-lymphotropic
      virus type 1 (HTLV-1) infectivity resulted in conflicting findings, and our
      knowledge of HTLV-1 restriction by other A3 proteins remains limited. Since HTLV
      1, much like HIV, targets CD4(+) T cells, we hypothesized that A3 proteins other
      than A3G restrict HTLV-1. All seven human A3 proteins were tested in HTLV-1
      reporter and HIV-1 infectivity assays. We show that A3A, A3B, and A3H haplotype 2
      (A3H hapII) acted as potent inhibitors of HTLV-1. Wild-type HIV-1, in contrast,
      was restricted by A3B and A3H hapII, but not by A3A. Catalytic site mutants of
      A3A, A3B, and A3H hapII showed that A3A and A3B restriction of HTLV-1 required
      deaminase activity. However, A3H hapII acted in a deaminase-independent manner
      when restricting HTLV-1, while requiring deaminase activity for HIV-1
      restriction. We also analyzed A3 editing of HTLV-1 in five T-cell lines obtained
      from HTLV-1-infected patients. These cell lines contained extensively edited HTLV
      1 sequences with G-to-A mutations in dinucleotide contexts suggestive of APOBEC3
      mutagenesis. Comparison of the A3-induced mutations from reporter cells and the
      patient-derived cell lines indicate that A3G but also other A3 members, possibly
      A3A and A3B, affect HTLV-1 in vivo. Taken together, our data indicate that HTLV-1
      is a likely target for multiple A3 proteins.

PMID- 22457531
TI  - Complete genome sequence of a highly prevalent porcine circovirus 2 isolated from
      piglet stool samples in China.
AB  - Porcine circovirus type 2 (PCV2) is the etiologic agent of porcine circovirus
      associated disease. Here, we first report the complete genome sequence of PCV2
      strain JSTZ, which was isolated from piglet stool samples and is highly prevalent
      in China. It will help in understanding the epidemiology and molecular
      characteristics of PCV2.

PMID- 22457532
TI  - Full genome sequence of bluetongue virus serotype 1 from India.
AB  - We report the full-genome sequence of an Indian isolate of bluetongue virus
      serotype 1 (BTV-1), strain IND1992/01. This is the first report of the entire
      genome sequence (Seg-1 to Seg-10) of an Eastern (e) strain of BTV-1. These
      sequence data provide a reference for BTV-1e that will help to define the
      phylogenetic relationships and geographic origins of distinct Indian lineages of
      BTV-1 as well as their relationships with other BTV strains from around the
      world. The availability of data for all 10 genome segments of this strain will
      also help to identify reassortment events involving this and other virus
      lineages.

PMID- 22457533
TI  - Metabolic flux increases glycoprotein sialylation: implications for cell adhesion
      and cancer metastasis.
AB  - This study reports a global glycoproteomic analysis of pancreatic cancer cells
      that describes how flux through the sialic acid biosynthetic pathway selectively
      modulates a subset of N-glycosylation sites found within cellular proteins. These
      results provide evidence that sialoglycoprotein patterns are not determined
      exclusively by the transcription of biosynthetic enzymes or the availability of N
      glycan sequons; instead, bulk metabolic flux through the sialic acid pathway has
      a remarkable ability to increase the abundance of certain sialoglycoproteins
      while having a minimal impact on others. Specifically, of 82 glycoproteins
      identified through a mass spectrometry and bioinformatics approach, ~ 31% showed
      no change in sialylation, ~ 29% exhibited a modest increase, whereas ~ 40%
      experienced an increase of greater than twofold. Increased sialylation of
      specific glycoproteins resulted in changes to the adhesive properties of SW1990
      pancreatic cancer cells (e.g. increased CD44-mediated adhesion to selectins under
      physiological flow and enhanced integrin-mediated cell mobility on collagen and
      fibronectin). These results indicate that cancer cells can become more
      aggressively malignant by controlling the sialylation of proteins implicated in
      metastatic transformation via metabolic flux.

PMID- 22457535
TI  - Spinal manipulative therapy and its role in the prevention, treatment and
      management of chronic pain.

PMID- 22457536
TI  - The CCRF Board is delighted to announce the recent appointments of Dr. Brynne
      Stainsby BA, DC and Dr. Ryan Larson BSc, DC to the Research Foundation.

PMID- 22457534
TI  - Proteomic analysis of microvesicles released by the human prostate cancer cell
      line PC-3.
AB  - Cancer biomarkers are invaluable tools for cancer detection, prognosis, and
      treatment. Recently, microvesicles have appeared as a novel source for cancer
      biomarkers. We present here the results from a proteomic analysis of
      microvesicles released to the extracellular environment by the metastatic
      prostate cancer cell line PC-3. Using nanocapillary liquid chromatography-tandem
      mass spectrometry 266 proteins were identified with two or more peptide
      sequences. Further analysis showed that 16% of the proteins were classified as
      extracellular and that intracellular proteins were annotated in a variety of
      locations. Concerning biological processes, the proteins found in PC-3 cell
      released microvesicles are mainly involved in transport, cell organization and
      biogenesis, metabolic process, response to stimulus, and regulation of biological
      processes. Several of the proteins identified (tetraspanins, annexins, Rab
      proteins, integrins, heat shock proteins, cytoskeletal proteins, 14-3-3 proteins)
      have previously been found in microvesicles isolated from other sources. However,
      some of the proteins seem to be more specific to the vesicular population
      released by the metastatic prostate cancer PC-3 cell line. Among these proteins
      are the tetraspanin protein CD151 and the glycoprotein CUB domain-containing
      protein 1. Interestingly, our results show these proteins are promising
      biomarkers for prostate cancer and therefore candidates for clinical validation
      studies in biological fluids.

PMID- 22457537
TI  - Use of post-isometric relaxation in the chiropractic management of a 55-year-old
      man with cervical radiculopathy.
AB  - This case report chronicles the successful management of a 55-year-old patient
      diagnosed with cervical radiculopathy using spinal manipulative therapy and
      cervical paraspinal post-isometric relaxation stretches.

PMID- 22457538
TI  - Cervical radiculopathy: a systematic review on treatment by spinal manipulation
      and measurement with the Neck Disability Index.
AB  - Cervical radiculopathy (CR), while less common than conditions with neck pain
      alone, can be a significant cause of neck pain and disability; thus the
      determination of adequate treatment options for patients is essential. Currently,
      inadequate scientific literature restricts specific conservative management
      recommendations for CR. Despite a paucity of evidence for high-velocity low
      amplitude (HVLA) spinal manipulation in the treatment for CR, this strategy has
      been frequently labeled as contraindicated. Scientific support for appropriate
      outcome measures for CR is equally deficient. While more scientific data is
      needed to draw firm conclusions, the present review suggests that spinal
      manipulation may be cautiously considered as a therapeutic option for patients
      suffering from CR. With respect to outcome measures, the Neck Disability Index
      appears well-suited for spinal manipulative treatment of CR.

PMID- 22457539
TI  - Conservative management of a lumbar compression fracture in an osteoporotic
      patient: a case report.
AB  - OBJECTIVE: To chronicle the conservative treatment and management of an
      osteoporotic patient presenting with acute back pain resulting from a lumbar
      compression fracture. CLINICAL FEATURES: A 74-year old male presented with acute
      back pain in the thoracolumbar region after an episode of lifting. Radiographic
      evaluation revealed generalized demineralization and a moderate wedge compression
      fracture at L1. INTERVENTION AND OUTCOME: The conservative treatment approach
      included postural education, activity modification, interferential current,
      taping into extension, Graston Technique((r)), and rehabilitative exercise
      prescription. Outcome measures included verbal pain rating scale, medication use,
      and a return to activities of daily living (ADLs). The patient attained long-term
      symptom resolution with no recurrence of pain at 12 month follow-up. SUMMARY: A
      combination of conservative rehabilitation strategies may be successfully
      implemented to treat osteoporotic patients with mild to moderate osteoporotic
      vertebral compression fracture of the lumbar spine.

PMID- 22457540
TI  - Prognostic significance of subgroup classification for infant patients with
      crying disorders: A prospective cohort study.
AB  - INTRODUCTION: Few convincing treatment options have been identified for the
      excessively crying infant. One explanation may be a lack of identification of
      patient subgroups. This study used a clinically plausible categorization protocol
      to subgroup infants and compared changes in symptoms between these subgroups
      during treatment. METHODS: An observational cohort design was employed. All
      infants presenting with excessive infant crying between July 2007 and March 2008
      were categorized into three subgroups, (A) infant colic, (B) irritable infant
      syndrome of musculoskeletal origin (IISMO) and (C) inefficient feeding crying
      infants with disordered sleep (IFCIDS) based on history and physical findings.
      Mothers completed questionnaires which rated their own and their child's
      characteristics prior to and at the end, of a course of manual therapy.
      Independent associations between infant subgroups and changes in continuous
      outcomes (crying, stress, sleep, and consolability) were assessed. Multivariable
      analysis of covariance was used to identify and control for potential
      confounders. RESULTS: A total of 158 infants were enrolled. There was no
      significant difference in demographic profile between groups or any significant
      difference in infant crying or level of maternal stress at the start. Only the
      putative subgroups were significantly associated with differences in outcomes. In
      general, colic babies improved the most in consolability and crying. CONCLUSION:
      Babies with excessive crying should not be viewed as a homogenous group.
      Treatment outcomes may be improved by targeting appropriate subgroups prior to
      treatment.

PMID- 22457541
TI  - Clinical effectiveness of the activator adjusting instrument in the management of
      musculoskeletal disorders: a systematic review of the literature.
AB  - OBJECTIVE: The purpose of this study was to conduct a systematic review of the
      literature investigating clinical outcomes involving the use of the Activator
      Adjusting Instrument (AAI) or Activator Methods Chiropractic Technique (AMCT).
      METHODS: A literature synthesis was performed on the available research and
      electronic databases, along with hand-searching of journals and reference
      tracking for any studies that investigated the AAI in terms of clinical
      effectiveness. Studies that met the inclusion criteria were evaluated using an
      instrument that assessed their methodological quality. RESULTS: Eight articles
      met the inclusion criteria. Overall, the AAI provided comparable clinically
      meaningful benefits to patients when compared to high-velocity, low-amplitude
      (HVLA) manual manipulation or trigger point therapy for patients with acute and
      chronic spinal pain, temporomandibular joint (TMJ) dysfunction and trigger points
      of the trapezius muscles. CONCLUSION: This systematic review of 8 clinical trials
      involving the use of the AAI found reported benefits to patients with a spinal
      pain and trigger points, although the clinical trials reviewed suffered from many
      methodological limitations, including small sample size, relatively brief follow
      up period and lack of control or sham treatment groups.

PMID- 22457542
TI  - Spontaneous conus medullaris infarction in a 79 year-old female with
      cardiovascular risk factors: a case report.
AB  - OBJECTIVE: To detail the case of a 79 year-old female who presented with sudden
      bilateral neurological deficits of the lower extremities and was later diagnosed
      with non-traumatic conus medullaris infarction. The purpose of this case report
      is to inform primary contact practitioners of the presentation, diagnosis and the
      associated risk factors of this condition in order to facilitate prompt
      management. CLINICAL FEATURES: Spinal cord infarction presenting as low back pain
      with a high degree of bilateral loss of motor strength, sensation and reflexes in
      the lower extremities and bowel/bladder dysfunction, in a patient with previous
      coronary artery bypass graft surgery and renal insufficiency. INTERVENTION AND
      OUTCOME: Referral to emergency within hours of symptom onset allowed for
      immediate assessment, management and relatively favourable partial recovery.
      SUMMARY: Although rare, conus medullaris infarction is potentially devastating
      and requires an appropriate clinical index of suspicion for timely diagnosis,
      treatment and optimal neurological recovery.

PMID- 22457544
TI  - Letters to the editor.

PMID- 22457543
TI  - Chiropractic leadership in the eradication of sexual abuse.
AB  - Health practitioners work under fiduciary constraint, and are obligated to favour
      patient needs over all others and in particular their own. The principles of
      professionalism demand that professionals take great care to ensure that
      boundaries are maintained safely to provide an optimal setting in facilitating
      patient care. Boundary violations cause serious harm to the patient. Any romantic
      or sexual activity between parties is the most serious form of boundary
      violation. The chiropractic profession is included in the list of disciplines
      which are at an increased risk for boundary violations. The authors propose a
      four stage protocol which is designed to offer all parties maximal protection
      beginning with undergraduate professional education and then mandatory continuing
      education for registrants in professional practice. The protocol would affect all
      aspects of professional life including training in boundaries and jurisdictional
      regulation.

PMID- 22457545
TI  - Design and Evaluation of Prophylactic Interventions Using Infectious Disease
      Incidence Data from Close Contact Groups.
AB  - Prophylaxis of contacts of infectious cases such as household members and
      treatment of infectious cases are methods to prevent spread of infectious
      diseases. We develop a method based on maximum likelihood to estimate the
      efficacy of such interventions and the transmission probabilities. We consider
      both the design with prospective follow-up of close contact groups and the design
      with ascertainment of close contact groups by an index case as well as
      randomization by groups and by individuals. We compare the designs using
      simulations. We estimate the efficacy of the influenza antiviral agent
      oseltamivir in reducing susceptibility and infectiousness in two case-ascertained
      household trials.

PMID- 22457546
TI  - Young Girls' and Caretakers' Reports of Problem Behavior: Comprehension and
      Concordance Across Age, Race, and Behavior.
AB  - The article discusses a research instrument developed and utilized by the
      Pittsburgh Girls Study that asked young girls (ages 7 and 8) and their caretakers
      to report on the girls' involvement in a variety of problem behaviors. In this
      article, the authors evaluate whether comprehension, prevalence, and caretaker
      child concordance of problem behaviors varied by child age and race. Results
      indicate that the girls understood most questions (except for some related to
      drug use) and that comprehension and reported involvement increased with age.
      Findings show that nonwhites showed greater comprehension and reported more
      involvement in problem behavior than Whites. Overall, the authors find modest
      concordance between reports from the girls and their caretakers, with greater
      agreement for nonwhites and older children. The authors conclude that a more
      comprehensive understanding of youth problem behavior is gained when both
      caretakers and children provide reports.

PMID- 22457547
TI  - Boswellia serrata, a potential antiinflammatory agent: an overview.
AB  - The resin of Boswellia species has been used as incense in religious and cultural
      ceremonies and in medicines since time immemorial. Boswellia serrata (Salai/Salai
      guggul), is a moderate to large sized branching tree of family Burseraceae (Genus
      Boswellia), grows in dry mountainous regions of India, Northern Africa and Middle
      East. Oleo gum-resin is tapped from the incision made on the trunk of the tree
      and is then stored in specially made bamboo basket for removal of oil content and
      getting the resin solidified. After processing, the gum-resin is then graded
      according to its flavour, colour, shape and size. In India, the States of Andhra
      Pradesh, Gujarat, Madhya Pradesh, Jharkhand and Chhattisgarh are the main source
      of Boswellia serrata. Regionally, it is also known by different names. The oleo
      gum-resins contain 30-60% resin, 5-10% essential oils, which are soluble in the
      organic solvents, and the rest is made up of polysaccharides. Gum-resin extracts
      of Boswellia serrata have been traditionally used in folk medicine for centuries
      to treat various chronic inflammatory diseases. The resinous part of Boswellia
      serrata possesses monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic
      acids and four major pentacyclic triterpenic acids i.e. beta-boswellic acid,
      acetyl-beta-boswellic acid, 11-keto-beta-boswellic acid and acetyl-11-keto-beta
      boswellic acid, responsible for inhibition of pro-inflammatory enzymes. Out of
      these four boswellic acids, acetyl-11-keto-beta-boswellic acid is the most potent
      inhibitor of 5-lipoxygenase, an enzyme responsible for inflammation.

PMID- 22457548
TI  - Revisiting curcumin chemistry part I: a new strategy for the synthesis of
      curcuminoids.
AB  - A new strategy for the synthesis of curcuminoids is described involving the
      reaction of acetylacetone difluroboronite with an aromatic aldehyde in the
      presence of n-butylamine as catalyst. The new intermediate products, curcuminoid
      difluroboronites, of symmetrically substituted curcuminoids like curcumin and
      bisdemethoxycurcumin are stable, can be isolated and hydrolysed with aq. methanol
      at pH 5.8 to get the curcuminoids of high purity. The method is applicable for
      unsymmetrical curcuminoids like demethoxycurcumin also with some modification
      involving column chromatography. The intermediate curcuminoid difluroboronites,
      as also the natural beta-diketone pongamol difluroboronite, prepared for the
      first time were characterized on the basis of physical and chemical properties
      and spectroscopic data. The advantage of using borontrifluoride to protect the
      enol group in acetylacetone over the generally used boric oxide is brought out.
      The importance of conducting biological activity studies using pure curcuminoids
      is explained.

PMID- 22457549
TI  - Enhancing hepatoprotective bioactives of phyllanthus amarus through
      immobilization by growth promoters and media changes.
AB  - The present paper describes enhancement of lignans, phyllanthin and
      hypophyllanthin present in Phyllanthus amarus plant. Supplementation was done to
      enhance secondary metabolites by modifying the media and treatment with different
      growth promoters and abiotic elicitors to increase the content of
      hepatoprotective bioactives in immobilized cell cultures, after incubation for 21
      days. MS medium was supplemented with gibberellic acid and to make whole process
      commercially viable, when coconut water, sugarcane juice and water-melon extract
      were treated, it was revealed that watermelon extract, enhances maximum
      phyllanthin and hypophyllanthin yield followed by sugarcane juice, coconut water
      and gibberellic acid after estimation by HPTLC. The present method was found to
      be accurate, economical and viable to enhance the content of phyllanthin and
      hypophyllanthin in P. amarus for large-scale commercial production.

PMID- 22457550
TI  - Preparation of evodiamine solid dispersions and its pharmacokinetics.
AB  - In order to increase the dissolution rate and bioavailability, solid dispersions
      of evodiamine in PVP K(30) with different enriched samples of evodiamine to PVP
      K(30) ratios were prepared by solvent method. Our studies showed that the
      dissolution rate of evodiamine was significantly higher in the solid dispersion
      system in comparison with that in enriched samples of evodiamine or physical
      mixtures. The increase of the dissolution rate was evidently related to the ratio
      of evodiamine to PVP K(30). The solid dispersion system (enriched samples of
      evodiamine/PVP K(30)= 1/6, w/w) gave the highest dissolution rate: about 27.7
      fold higher than that of enriched samples of evodiamine in hard capsules. Powder
      X-ray diffraction studies showed that enriched samples of evodiamine presented a
      total chemical stability after its preparation as solid dispersions. In vivo
      administration studies indicated that solid dispersions of evodiamine in hard
      capsules had a higher C(max) and a shorter T(max) than those of physical mixture
      in hard capsules, and the differences of C(max) and T(max) between them were
      significant. These results suggest that solid dispersions of evodiamine in hard
      capsules has a notably faster and greater absorption rate than enriched samples
      of evodiamine in physical mixture hard capsule and corresponds with the in vitro
      dissolution.

PMID- 22457551
TI  - Comparison of aerosol formulations of formoterol fumarate and budesonide.
AB  - The aerodynamic diameter of pharmaceutical aerosols is the main factor governing
      their deposition in the human respiratory tract. Particle size of the
      pharmaceutical aerosols is characterized by liquid impingers and Andersen Cascade
      Impactors. The present study was aimed at comparing two metered dose inhaler
      formulation containing formoterol fumarate (6 MUg) and budesonide (200 MUg).
      These two formulations were evaluated by using Twin Stage Impinger and Andersen
      Cascade Impactor. Study revealed that developed metered dose inhaler I
      formulation of the formoterol fumarate and budesonide had lower mass median
      aerodynamic diameter and higher fine particle fraction than marketed formulation.

PMID- 22457552
TI  - Identification of Forced Degradation Products of Itopride by LC-PDA and LC-MS.
AB  - Degradation products of itopride formed under different forced conditions have
      been identified using LC-PDA and LC-MS techniques. Itopride was subjected to
      forced degradation under the conditions of hydrolysis, photolysis, oxidation, dry
      and wet heat, in accordance with the International Conference on Harmonization.
      The stress solutions were chromatographed on reversed phase C18 (250*4.6 mm, 5
      MUm) column with a mobile phase methanol:water (55:45, v/v) at a detection
      wavelength of 215 nm. Itopride degraded in acid, alkali and oxidative stress
      conditions. The stability indicating method was developed and validated. The
      degradation pathway of the drug to products II-VIII is proposed.

PMID- 22457553
TI  - Synthesis, antimicrobial and antioxidant activity of some oxindoles.
AB  - The present work describes the synthesis and spectral analysis of some new 3(Z)
      {4-[4-(arylsulfonyl)piperazin-1-ylbenzylidene)-1,3-dihydro-2H-indol-2-one (5a-j).
      Ten of the synthesized compounds were screened in vitro against six species of
      microorganisms, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli,
      Pseudomonas aeruginosa, Asperigellus niger and Asperigellus clavatus. Most of the
      compounds exhibited significant antimicrobial activity. All of these compounds
      were also screened in vitro for the antioxidant activity using DPPH assay. Most
      of them have shown very significant antioxidant activity.

PMID- 22457554
TI  - Development and validation of simultaneous spectrophotometric methods for
      drotaverine hydrochloride and aceclofenac from tablet dosage form.
AB  - Two simple spectrophotometric methods have been developed for simultaneous
      estimation of drotaverine hydrochloride and aceclofenac from tablet dosage form.
      Method I is a simultaneous equation method (Vierodt's method), wavelengths
      selected are 306.5 and 276 nm. Method II is the absorbance ratio method (Q
      Analysis), which employs 298.5 nm as lambda(1) and 276 nm as lambda(2) (lambdamax
      of AF) for formation of equations. Both the methods were found to be linear
      between the range of 8-32 MUg/ml for drotaverine and 10-40 MUg/ml for
      aceclofenac. The accuracy and precision were determined and found to comply with
      ICH guidelines. Both the methods showed good reproducibility and recovery with %
      RSD in the desired range. The methods were found to be rapid, specific, precise
      and accurate and can be successfully applied for the routine analysis of
      drotaverine and aceclofenac in their combined tablet dosage form.

PMID- 22457555
TI  - Role of butea frondosa in ameliorating gastric markers in induced gastric lesions
      of rats.
AB  - The study evaluated the ability of the alcohol extract of Butea frondosa to
      protect the gastro-duodenal lining from injury inflicted by acetic acid and
      pyloric ligation in rats. The induced gastric lesions lead to the generation of
      alkaline phosphatase and pepsin, which serve as important markers of gastric
      damage. Alcohol extract of Butea frondosa was administered in doses of 10, 100,
      300 and 500 mg/kg as a single schedule and for the time dependent studies in a
      dose of 100 mg/kg for 7, 14, 21 and 28 days, respectively. Our studies reveal a
      decline in the formation of alkaline phosphatase and pepsin with 300 and 500
      mg/kg of the extract and following treatment for 21 and 28 days, respectively.
      Extract of Butea frondosa produces significant diminution in the formation of
      gastric markers implying possible gastro-protective action.

PMID- 22457556
TI  - Evaluation of wound healing potential of topical formulation of leaf juice of
      tridax procumbens L. In mice.
AB  - Tridax procumbens L. (Compositae) is a common weed that grows in the rice fields
      of India. Traditionally the juice from leaves of Tridax procumbens has been used
      for healing dermal wound. However, in experimental studies, equivocal pro and
      anti-healing action of T. procumbens has been demonstrated. The present study
      evaluates the effect of topical ointment formulation of the leaf juice of T.
      procumbens using excision wound model in mice. Excision wounds (4 mm, i.d.) were
      inflicted on depilated back of mice. Ointment formulation of TP (50 mg of either
      1 or 4 mg/g) was applied twice daily for 4 days on the dermal wound. Similarly,
      control group was treated with VEGF ointment (50 mg of 1 MUg/g). The parameters
      observed were re-epithelization, vascularity, fibroblast number, collagen
      content. The healing exerted by TP (1 mg/g) was comparable to VEGF (1 MUg/g). On
      the other hand, TP (4 mg/g) induced inflammation, edematous tissue and decreased
      vascularity. Taken together, the results imply that TP possesses dose dependent
      pro-healing potential, and its high dose exerts inflammatory reaction.

PMID- 22457557
TI  - Diuretic effects of young fruit extracts of bombax ceiba L. In rats.
AB  - The present study was aimed to investigate the diuretic effects of aqueous and
      crude ethanol extracts of Bombax ceiba L. fruits (family, Bombacaceae) using
      acute model in rats. A single individual dose of aqueous and ethanol extract of
      B. ceiba fruit (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 pairs and
      their urine output was monitored at 5 and 24 h intervals. 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 aqueous
      extract (400 mg/kg) in 5 h was almost similar to that of frusemide and
      hydrochlothiazide. Aqueous extract of B. ceiba fruit 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 B. ceiba fruits. These effects demonstrate possible diuretic actions
      of B. ceiba fruit extracts and support its folklore use in various urinary
      ailments. Further studies need to be done to characterize the active
      phytoconstituents from fruits.

PMID- 22457558
TI  - Microencapsulation of eugenol by gelatin-sodium alginate complex coacervation.
AB  - Present study describes microencapsulation of eugenol using gelatin-sodium
      alginate complex coacervation. The effects of core to coat ratio and drying
      method on properties of the eugenol microcapsules were investigated. The eugenol
      microcapsules were evaluated for surface characteristics, micromeritic
      properties, oil loading and encapsulation efficiency. Eugenol microcapsules
      possessed good flow properties, thus improved handling. The scanning electron
      photomicrographs showed globular surface of microcapsules prepared with core:
      coat ratio1:1.The treatment with dehydrating agent isopropanol lead to shrinking
      of microcapsule wall with cracks on it. The percent oil loading and encapsulation
      efficiency increased with increase in core: coat ratio whereas treatment with
      dehydrating agent resulted in reduction in loading and percent encapsulation
      efficiency of eugenol microcapsules.

PMID- 22457559
TI  - Extended hildebrand solubility approach: satranidazole in mixtures of dioxane and
      water.
AB  - The extended Hildebrand solubility parameter approach is used to estimate the
      solubility of satranidazole in binary solvent systems. The solubility of
      satranidazole in various dioxane-water mixtures was analyzed in terms of solute
      solvent interactions using a modified version of Hildebrand-Scatchard treatment
      for regular solutions. The solubility of satranidazole in the binary solvent,
      dioxane-water shows a bell-shaped profile with a solubility maximum well above
      the ideal solubility of the drug. This is attributed to solvation of the drug
      with the dioxane-water mixture, and indicates that the solute-solvent interaction
      energy is larger than the geometric mean (delta(1)delta(2)) of regular solution
      theory. The new approach provides an accurate prediction of solubility once the
      interaction energy is obtained. In this case, the energy term is regressed
      against a polynomial in delta(1) of the binary mixture. A quartic expression of W
      in terms of solvent solubility parameter was found for predicting the solubility
      of satranidazole in dioxane-water mixtures. The method has potential usefulness
      in preformulation and formulation studies during which solubility prediction is
      important for drug design.

PMID- 22457560
TI  - A Sensitive RP-HPLC Method for Simultaneous Estimation of Diethylcarbamazine and
      Levocetirizine in Tablet Formulation.
AB  - A simple, sensitive and reproducible method was developed and validated for the
      simultaneous estimation of diethylcarbamazine and levocetirizine in its tablet
      formulation by reverse phase high performance liquid chromatography using
      Waters1515 HPLC with UV detector at the lambda(max) of 224 nm, using Princeton
      Sphere-100 C(18) (250*4.6 mm. 5 MU) column. The mobile phase used was 20mM
      potassium dihydrogen orthophosphate buffer (pH: 3.2):acetonitrile (50:50 v/v)
      with isocratic flow (flow rate 1 ml/min) and the pH was adjusted with
      orthophosphoric acid. Losartan potassium was used as an internal standard. The
      compounds diethylcarbamazine, levocetirizine and losartan potassium were eluted
      at 2.12, 4.27 and 5.96 min, respectively. The peaks were eluted with better
      resolution. The method was accurate with assay values of 96.32 and 93.04% w/w,
      precise (%RSD) with intra-day 1.72 and 1.89 and inter-day 1.85 and 1.92,
      recoveries 102.86 and 101.1% w/w, which are very sensitive with limit of
      detections (LOD)'s 75, 50 ng/ml and limit of quantification (LOQ)'s 100, 75 ng/ml
      and linear with R(2) values 0.994 in the range of 5 to 30 MUg/ml 0.1 to 1 MUg/ml
      for diethylcarbamazine and levocetirizine, respectively. Hence this method can be
      applied for quantification of different formulations containing
      diethylcarbamazine and levocetirizine simultaneously.

PMID- 22457561
TI  - Formulation and evaluation of niosomes.
AB  - Span 20-based niosome was prepared by lipid film hydration technique and loaded
      with Newcastle disease vaccine. Three batches with Span 20, cholesterol and
      dicetyl phosphate in micro molar ratios of 10:10:1; 15:15:1 and 20:20:1 were
      prepared and evaluated for encapsulation efficiency using haemagglutination test.
      The morphology of the vesicles was studied by means of transmission electron
      microscopy. Particle size, zeta potential and polydispersity index were
      determined by photon correlation spectroscopy using a nanosizer. Adjuvanticity
      was assessed using haemagglutination inhibition test. The vesicles of Span 20
      based niosomes were distinct, near spherical large unilamellar vesicles. The
      vesicles were of varied sizes (<1000 nm) with the entrapped Newcastle disease
      vaccine in the core of the vaccine. The zeta potential had a peak at -50 mV. The
      polydispersity index was 0.68. Haemagglutination inhibition test showed a 71%
      increment in immune response over that of the marketed La Sota((r)) vaccine which
      had a 60% increment in immune response. The niosomal vaccine did not alter but
      rather enhanced the immunogenicity of the Newcastle disease vaccine.

PMID- 22457562
TI  - Evaluation of the antibacterial and antidiarrhoeal activities of heeria insignis
      o. Ktze.
AB  - Heeria insignis O. Ktze (Anacardiaceae) is an indigenous African shrub used in
      treatment of diarrhea, venereal diseases, tapeworm, hookworm, schistosomiasis,
      kidney trouble and for increasing lactation in women after childbirth. The
      methanol and dichloromethane extracts of the leaves were evaluated for
      antibacterial activity (using agar-diffusion method) and antidairrheal activity
      (using isolated rabbit jejunum and castor-oil induced diarrhea in mice). The
      methanol extract gave higher antibacterial activity than dichloromethane. The
      order of susceptibility of test microorganisms to methanol extract were
      Salmonella typhi>Pseudomous aeruginosa> Staphylococcus aureus>Bacillus
      subtilis>Escherichia coli which were comparable to standard. The minimum
      inhibitory concentration of the methanol extract for these microorganisms was
      also determined. The minimum inhibitory concentration (mg/ml) of methanol extract
      against microorganisms is; B. subtilis (3.9), S. aureus (1.95), E. coli (62.5),
      Ps. aeruginosa (3.9) and S. typhi (1.95). On the isolated rabbit jejunum
      evaluation, both extracts produced concentration-dependent relation of isolated
      rabbit jejunum that was not blocked by phentolamine, suggesting that extracts act
      via mechanisms other than alpha-adrenergic receptor. In the castor oil-induced
      diarrheoeal test, each extract gave 80% protection at 200 mg/kg, which is
      comparable to loperamide 2 mg/kg with 80% protection. This finding may explain
      the use of the plant in diarrhea and bacterial diseases.

PMID- 22457563
TI  - New 6-Bromo-2-Methyl-3-(Substituted Phenyl)-(3H)-Quinazolin-4-Ones with
      Antimicrobial and Antiinflammatory Activities.
AB  - New quinazolin-4-one derivatives, 6-bromo-2-methyl-3-(substituted phenyl)-(3H)
      quinazolin-4-one, were synthesized and evaluated for antimicrobial and
      antiinflammatory activities. The structures attributed to synthesized compounds 1
      8 were supported by the results of elemental analysis as well as by the UV, IR
      and (1)H NMR spectral data. Investigation of antimicrobial activity was performed
      using cup-plate agar diffusion method against Bacillus subtilis, Staphylococcus
      aureus and Pseudomonas aeruginosa and Candida albicans, Aspergillus niger and
      Curvularia lunata. Antiinflammatory activity was evaluated using the carrageenan
      induced paw oedema test in rats. The results showed that compounds 2b, 2c, 2d, 2g
      and 2h exhibited significant antibacterial and antifungal activity comparable to
      standard drugs and compounds 2b and 2c showed good antiinflammatory activity
      comparable to ibuprofen.

PMID- 22457564
TI  - Both Risk and Reward are Processed Differently in Decisions Made Under Stress.
AB  - Years of research show that stress influences cognition. Most of this research
      has focused on how stress affects memory and the hippocampus. However, stress
      impacts other regions involved in cognitive and emotional processing, including
      the prefrontal cortex, striatum, and insula. New research examining how stress
      affects decision processes reveals two consistent findings. First, acute stress
      enhances selection of previously rewarding outcomes but impairs selection of
      previously negative outcomes, possibly due to stress-induced changes in dopamine
      in reward-processing brain regions. Second, stress amplifies gender differences
      in strategies during risky decisions, with males taking more risk and females
      less risk under stress. These gender differences in behavior are associated with
      differences in activity in the insula and dorsal striatum, brain regions involved
      in computing risk and preparing to take action.

PMID- 22457565
TI  - The Role of Headwater Streams in Downstream Water Quality.
AB  - Knowledge of headwater influences on the water-quality and flow conditions of
      downstream waters is essential to water-resource management at all governmental
      levels; this includes recent court decisions on the jurisdiction of the Federal
      Clean Water Act (CWA) over upland areas that contribute to larger downstream
      water bodies. We review current watershed research and use a water-quality model
      to investigate headwater influences on downstream receiving waters. Our
      evaluations demonstrate the intrinsic connections of headwaters to landscape
      processes and downstream waters through their influence on the supply, transport,
      and fate of water and solutes in watersheds. Hydrological processes in headwater
      catchments control the recharge of subsurface water stores, flow paths, and
      residence times of water throughout landscapes. The dynamic coupling of
      hydrological and biogeochemical processes in upland streams further controls the
      chemical form, timing, and longitudinal distances of solute transport to
      downstream waters. We apply the spatially explicit, mass-balance watershed model
      SPARROW to consider transport and transformations of water and nutrients
      throughout stream networks in the northeastern United States. We simulate fluxes
      of nitrogen, a primary nutrient that is a water-quality concern for acidification
      of streams and lakes and eutrophication of coastal waters, and refine the model
      structure to include literature observations of nitrogen removal in streams and
      lakes. We quantify nitrogen transport from headwaters to downstream navigable
      waters, where headwaters are defined within the model as first-order, perennial
      streams that include flow and nitrogen contributions from smaller, intermittent
      and ephemeral streams. We find that first-order headwaters contribute
      approximately 70% of the mean-annual water volume and 65% of the nitrogen flux in
      second-order streams. Their contributions to mean water volume and nitrogen flux
      decline only marginally to about 55% and 40% in fourth- and higher-order rivers
      that include navigable waters and their tributaries. These results underscore the
      profound influence that headwater areas have on shaping downstream water quantity
      and water quality. The results have relevance to water-resource management and
      regulatory decisions and potentially broaden understanding of the spatial extent
      of Federal CWA jurisdiction in U.S. waters.

PMID- 22457566
TI  - Linking Hydrologic Alteration to Biological Impairment in Urbanizing Streams of
      the Puget Lowland, Washington, USA.
AB  - We used a retrospective approach to identify hydrologic metrics with the greatest
      potential for ecological relevance for use as resource management tools (i.e.,
      hydrologic indicators) in rapidly urbanizing basins of the Puget Lowland. We
      proposed four criteria for identifying useful hydrologic indicators: (1)
      sensitive to urbanization consistent with expected hydrologic response, (2)
      demonstrate statistically significant trends in urbanizing basins (and not in
      undeveloped basins), (3) be correlated with measures of biological response to
      urbanization, and (4) be relatively insensitive to potentially confounding
      variables like basin area. Data utilized in the analysis included gauged flow and
      benthic macroinvertebrate data collected at 16 locations in 11 King County stream
      basins. Fifteen hydrologic metrics were calculated from daily average flow data
      and the Pacific Northwest Benthic Index of Biological Integrity (B-IBI) was used
      to represent the gradient of response of stream macroinvertebrates to
      urbanization. Urbanization was represented by percent Total Impervious Area
      (%TIA) and percent urban land cover (%Urban). We found eight hydrologic metrics
      that were significantly correlated with B-IBI scores (Low Pulse Count and
      Duration; High Pulse Count, Duration, and Range; Flow Reversals, T(Qmean), and R
      B Index). Although there appeared to be a great deal of redundancy among these
      metrics with respect to their response to urbanization, only two of the metrics
      tested - High Pulse Count and High Pulse Range - best met all four criteria we
      established for selecting hydrologic indicators. The increase in these high pulse
      metrics with respect to urbanization is the result of an increase in winter high
      pulses and the occurrence of high pulse events during summer (increasing the
      frequency and range of high pulses), when practically none would have occurred
      prior to development. We performed an initial evaluation of the usefulness of our
      hydrologic indicators by calculating and comparing hydrologic metrics derived
      from continuous hydrologic simulations of selected basin management alternatives
      for Miller Creek, one of the most highly urbanized basins used in our study. We
      found that the preferred basin management alternative appeared to be effective in
      restoring some flow metrics close to simulated fully forested conditions (e.g.,
      T(Qmean)), but less effective in restoring other metrics such as High Pulse Count
      and Range. If future research continues to support our hypothesis that the flow
      regime, particularly High Pulse Count and Range, is an important control of
      biotic integrity in Puget Lowland streams, it would have significant implications
      for stormwater management.

PMID- 22457567
TI  - Incorporating Uncertainty Into the Ranking of SPARROW Model Nutrient Yields From
      Mississippi/Atchafalaya River Basin Watersheds.
AB  - Excessive loads of nutrients transported by tributary rivers have been linked to
      hypoxia in the Gulf of Mexico. Management efforts to reduce the hypoxic zone in
      the Gulf of Mexico and improve the water quality of rivers and streams could
      benefit from targeting nutrient reductions toward watersheds with the highest
      nutrient yields delivered to sensitive downstream waters. One challenge is that
      most conventional watershed modeling approaches (e.g., mechanistic models) used
      in these management decisions do not consider uncertainties in the predictions of
      nutrient yields and their downstream delivery. The increasing use of parameter
      estimation procedures to statistically estimate model coefficients, however,
      allows uncertainties in these predictions to be reliably estimated. Here, we use
      a robust bootstrapping procedure applied to the results of a previous application
      of the hybrid statistical/mechanistic watershed model SPARROW (Spatially
      Referenced Regression On Watershed attributes) to develop a statistically
      reliable method for identifying "high priority" areas for management, based on a
      probabilistic ranking of delivered nutrient yields from watersheds throughout a
      basin. The method is designed to be used by managers to prioritize watersheds
      where additional stream monitoring and evaluations of nutrient-reduction
      strategies could be undertaken. Our ranking procedure incorporates information on
      the confidence intervals of model predictions and the corresponding watershed
      rankings of the delivered nutrient yields. From this quantified uncertainty, we
      estimate the probability that individual watersheds are among a collection of
      watersheds that have the highest delivered nutrient yields. We illustrate the
      application of the procedure to 818 eight-digit Hydrologic Unit Code watersheds
      in the Mississippi/Atchafalaya River basin by identifying 150 watersheds having
      the highest delivered nutrient yields to the Gulf of Mexico. Highest delivered
      yields were from watersheds in the Central Mississippi, Ohio, and Lower
      Mississippi River basins. With 90% confidence, only a few watersheds can be
      reliably placed into the highest 150 category; however, many more watersheds can
      be removed from consideration as not belonging to the highest 150 category.
      Results from this ranking procedure provide robust information on watershed
      nutrient yields that can benefit management efforts to reduce nutrient loadings
      to downstream coastal waters, such as the Gulf of Mexico, or to local receiving
      streams and reservoirs.

PMID- 22457568
TI  - Influence of Environmental Factors on Biotic Responses to Nutrient Enrichment in
      Agricultural Streams.
AB  - The influence of environmental factors on biotic responses to nutrients was
      examined in three diverse agricultural regions of the United States. Seventy
      wadeable sites were selected along an agricultural land use gradient while
      minimizing natural variation within each region. Nutrients, habitat, algae,
      macroinvertebrates, and macrophyte cover were sampled during a single summer low
      flow period in 2006 or 2007. Continuous stream stage and water temperature were
      collected at each site for 30 days prior to sampling. Wide ranges of
      concentrations were found for total nitrogen (TN) (0.07-9.61 mg/l) and total
      phosphorus (TP) (<0.004-0.361 mg/l), but biotic responses including periphytic
      and sestonic chlorophyll a (RCHL and SCHL, respectively), and percent of stream
      bed with aquatic macrophyte (AQM) growth were not strongly related to
      concentrations of TN or TP. Pearson's coefficient of determination (R(2)) for
      nutrients and biotic measures across all sites ranged from 0.08 to 0.32 and
      generally were not higher within each region. The biotic measures (RCHL, SCHL,
      and AQM) were combined in an index to evaluate eutrophic status across sites that
      could have different biotic responses to nutrient enrichment. Stepwise multiple
      regression identified TN, percent canopy, median riffle depth, and daily percent
      change in stage as significant factors for the eutrophic index (R(2) = 0.50, p <
      0.001). A TN threshold of 0.48 mg/l was identified where eutrophic index scores
      became less responsive to increasing TN concentrations, for all sites. Multiple
      plant growth indicators should be used when evaluating eutrophication, especially
      when streams contain an abundance of macrophytes.

PMID- 22457569
TI  - Weighted Regressions on Time, Discharge, and Season (WRTDS), with an Application
      to Chesapeake Bay River Inputs.
AB  - A new approach to the analysis of long-term surface water-quality data is
      proposed and implemented. The goal of this approach is to increase the amount of
      information that is extracted from the types of rich water-quality datasets that
      now exist. The method is formulated to allow for maximum flexibility in
      representations of the long-term trend, seasonal components, and discharge
      related components of the behavior of the water-quality variable of interest. It
      is designed to provide internally consistent estimates of the actual history of
      concentrations and fluxes as well as histories that eliminate the influence of
      year-to-year variations in streamflow. The method employs the use of weighted
      regressions of concentrations on time, discharge, and season. Finally, the method
      is designed to be useful as a diagnostic tool regarding the kinds of changes that
      are taking place in the watershed related to point sources, groundwater sources,
      and surface-water nonpoint sources. The method is applied to datasets for the
      nine large tributaries of Chesapeake Bay from 1978 to 2008. The results show a
      wide range of patterns of change in total phosphorus and in dissolved nitrate
      plus nitrite. These results should prove useful in further examination of the
      causes of changes, or lack of changes, and may help inform decisions about future
      actions to reduce nutrient enrichment in the Chesapeake Bay and its
      watershed.Hirsch, Robert M., Douglas L. Moyer, and Stacey A. Archfield, 2010.
      Weighted Regressions on Time, Discharge, and Season (WRTDS), With an Application
      to Chesapeake Bay River Inputs. Journal of the American Water Resources
      Association (JAWRA) 46(5):857-880. DOI: 10.1111/j.1752-1688.2010.00482.x.

PMID- 22457570
TI  - Trends in Pesticide Concentrations in Streams of the Western United States, 1993
      2005.
AB  - Trends in pesticide concentrations for 15 streams in California, Oregon,
      Washington, and Idaho were determined for the organophosphate insecticides
      chlorpyrifos and diazinon and the herbicides atrazine, s-ethyl
      diproplythiocarbamate (EPTC), metolachlor, simazine, and trifluralin. A
      parametric regression model was used to account for flow, seasonality, and
      antecedent hydrologic conditions and thereby estimate trends in pesticide
      concentrations in streams arising from changes in use amount and application
      method in their associated catchments. Decreasing trends most often were observed
      for diazinon, and reflect the shift to alternative pesticides by farmers,
      commercial applicators, and homeowners because of use restrictions and product
      cancelation. Consistent trends were observed for several herbicides, including
      upward trends in simazine at urban-influenced sites from 2000 to 2005, and
      downward trends in atrazine and EPTC at agricultural sites from the mid-1990s to
      2005. The model provided additional information about pesticide occurrence and
      transport in the modeled streams. Two examples are presented and briefly
      discussed: (1) timing of peak concentrations for individual compounds varied
      greatly across this geographic gradient because of different application periods
      and the effects of local rain patterns, irrigation, and soil drainage and (2)
      reconstructions of continuous diazinon concentrations at sites in California are
      used to evaluate compliance with total maximum daily load targets.

PMID- 22457571
TI  - Modeling the Potential Impact of Seasonal and Inactive Multi-Aquifer Wells on
      Contaminant Movement to Public Water-Supply Wells.
AB  - Wells screened across multiple aquifers can provide pathways for the movement of
      surprisingly large volumes of groundwater to confined aquifers used for public
      water supply (PWS). Using a simple numerical model, we examine the impact of
      several pumping scenarios on leakage from an unconfined aquifer to a confined
      aquifer and conclude that a single inactive multi-aquifer well can contribute
      nearly 10% of total PWS well flow over a wide range of pumping rates. This
      leakage can occur even when the multi-aquifer well is more than a kilometer from
      the PWS well. The contribution from multi-aquifer wells may be greater under
      conditions where seasonal pumping (e.g., irrigation) creates large, widespread
      downward hydraulic gradients between aquifers. Under those conditions, water can
      continue to leak down a multi-aquifer well from an unconfined aquifer to a
      confined aquifer even when those multi-aquifer wells are actively pumped. An
      important implication is that, if an unconfined aquifer is contaminated, multi
      aquifer wells can increase the vulnerability of a confined-aquifer PWS well.

PMID- 22457572
TI  - The Impacts of Water Conservation Strategies on Water Use: Four Case Studies.
AB  - We assessed impacts on water use achieved by implementation of controlled
      experiments relating to four water conservation strategies in four towns within
      the Ipswich watershed in Massachusetts. The strategies included (1) installation
      of weather-sensitive irrigation controller switches (WSICS) in residences and
      municipal athletic fields; (2) installation of rainwater harvesting systems in
      residences; (3) two outreach programs: (a) free home indoor water use audits and
      water fixture retrofit kits and (b) rebates for low-water-demand toilets and
      washing machines; and (4) soil amendments to improve soil moisture retention at a
      municipal athletic field. The goals of this study are to summarize the
      effectiveness of the four water conservation strategies and to introduce
      nonparametric statistical methods for evaluating the effectiveness of these
      conservation strategies in reducing water use. It was found that (1) the
      municipal WSICS significantly reduced water use; (2) residences with high
      irrigation demand were more likely than low water users to experience a
      substantial demand decrease when equipped with the WSICS; (3) rainwater
      harvesting provided substantial rainwater use, but these volumes were small
      relative to total domestic water use and relative to the natural fluctuations in
      domestic water use; (4) both the audits/retrofit and rebate programs resulted in
      significant water savings; and (5) a modeling approach showed potential water
      savings from soil amendments in ball fields.

PMID- 22457573
TI  - Sparrow Modeling to Understand Water-Quality Conditions in Major Regions of the
      United States: A Featured Collection Introduction.

PMID- 22457574
TI  - Factors Affecting Stream Nutrient Loads: A Synthesis of Regional SPARROW Model
      Results for the Continental United States.
AB  - We compared the results of 12 recently calibrated regional SPARROW (SPAtially
      Referenced Regressions On Watershed attributes) models covering most of the
      continental United States to evaluate the consistency and regional differences in
      factors affecting stream nutrient loads. The models - 6 for total nitrogen and 6
      for total phosphorus - all provide similar levels of prediction accuracy, but
      those for major river basins in the eastern half of the country were somewhat
      more accurate. The models simulate long-term mean annual stream nutrient loads as
      a function of a wide range of known sources and climatic (precipitation,
      temperature), landscape (e.g., soils, geology), and aquatic factors affecting
      nutrient fate and transport. The results confirm the dominant effects of urban
      and agricultural sources on stream nutrient loads nationally and regionally, but
      reveal considerable spatial variability in the specific types of sources that
      control water quality. These include regional differences in the relative
      importance of different types of urban (municipal and industrial point vs.
      diffuse urban runoff) and agriculture (crop cultivation vs. animal waste)
      sources, as well as the effects of atmospheric deposition, mining, and background
      (e.g., soil phosphorus) sources on stream nutrients. Overall, we found that the
      SPARROW model results provide a consistent set of information for identifying the
      major sources and environmental factors affecting nutrient fate and transport in
      United States watersheds at regional and subregional scales.

PMID- 22457575
TI  - Digital Hydrologic Networks Supporting Applications Related to Spatially
      Referenced Regression Modeling.
AB  - Digital hydrologic networks depicting surface-water pathways and their associated
      drainage catchments provide a key component to hydrologic analysis and modeling.
      Collectively, they form common spatial units that can be used to frame the
      descriptions of aquatic and watershed processes. In addition, they provide the
      ability to simulate and route the movement of water and associated constituents
      throughout the landscape. Digital hydrologic networks have evolved from
      derivatives of mapping products to detailed, interconnected, spatially referenced
      networks of water pathways, drainage areas, and stream and watershed
      characteristics. These properties are important because they enhance the ability
      to spatially evaluate factors that affect the sources and transport of water
      quality constituents at various scales. SPAtially Referenced Regressions On
      Watershed attributes (SPARROW), a process-based/statistical model, relies on a
      digital hydrologic network in order to establish relations between quantities of
      monitored contaminant flux, contaminant sources, and the associated physical
      characteristics affecting contaminant transport. Digital hydrologic networks
      modified from the River Reach File (RF1) and National Hydrography Dataset (NHD)
      geospatial datasets provided frameworks for SPARROW in six regions of the
      conterminous United States. In addition, characteristics of the modified RF1 were
      used to update estimates of mean-annual streamflow. This produced more current
      flow estimates for use in SPARROW modeling.

PMID- 22457576
TI  - A Multi-Agency Nutrient Dataset Used to Estimate Loads, Improve Monitoring
      Design, and Calibrate Regional Nutrient SPARROW Models.
AB  - Stream-loading information was compiled from federal, state, and local agencies,
      and selected universities as part of an effort to develop regional SPAtially
      Referenced Regressions On Watershed attributes (SPARROW) models to help describe
      the distribution, sources, and transport of nutrients in streams throughout much
      of the United States. After screening, 2,739 sites, sampled by 73 agencies, were
      identified as having suitable data for calculating long-term mean annual nutrient
      loads required for SPARROW model calibration. These sites had a wide range in
      nutrient concentrations, loads, and yields, and environmental characteristics in
      their basins. An analysis of the accuracy in load estimates relative to site
      attributes indicated that accuracy in loads improve with increases in the number
      of observations, the proportion of uncensored data, and the variability in flow
      on observation days, whereas accuracy declines with increases in the root mean
      square error of the water-quality model, the flow-bias ratio, the number of days
      between samples, the variability in daily streamflow for the prediction period,
      and if the load estimate has been detrended. Based on compiled data, all areas of
      the country had recent declines in the number of sites with sufficient water
      quality data to compute accurate annual loads and support regional modeling
      analyses. These declines were caused by decreases in the number of sites being
      sampled and data not being entered in readily accessible databases.

PMID- 22457577
TI  - Nutrient Loadings to Streams of the Continental United States from Municipal and
      Industrial Effluent.
AB  - Data from the United States Environmental Protection Agency Permit Compliance
      System national database were used to calculate annual total nitrogen (TN) and
      total phosphorus (TP) loads to surface waters from municipal and industrial
      facilities in six major regions of the United States for 1992, 1997, and 2002.
      Concentration and effluent flow data were examined for approximately 118,250
      facilities in 45 states and the District of Columbia. Inconsistent and incomplete
      discharge locations, effluent flows, and effluent nutrient concentrations limited
      the use of these data for calculating nutrient loads. More concentrations were
      reported for major facilities, those discharging more than 1 million gallons per
      day, than for minor facilities, and more concentrations were reported for TP than
      for TN. Analytical methods to check and improve the quality of the Permit
      Compliance System data were used. Annual loads were calculated using "typical
      pollutant concentrations" to supplement missing concentrations based on the type
      and size of facilities. Annual nutrient loads for over 26,600 facilities were
      calculated for at least one of the three years. Sewage systems represented 74% of
      all TN loads and 58% of all TP loads. This work represents an initial set of data
      to develop a comprehensive and consistent national database of point-source
      nutrient loads. These loads can be used to inform a wide range of water-quality
      management, watershed modeling, and research efforts at multiple scales.

PMID- 22457578
TI  - Source and Delivery of Nutrients to Receiving Waters in the Northeastern and Mid
      Atlantic Regions of the United States.
AB  - This study investigates nutrient sources and transport to receiving waters, in
      order to provide spatially detailed information to aid water-resources managers
      concerned with eutrophication and nutrient management strategies. SPAtially
      Referenced Regressions On Watershed attributes (SPARROW) nutrient models were
      developed for the Northeastern and Mid-Atlantic (NE US) regions of the United
      States to represent source conditions for the year 2002. The model developed to
      examine the source and delivery of nitrogen to the estuaries of nine large rivers
      along the NE US Seaboard indicated that agricultural sources contribute the
      largest percentage (37%) of the total nitrogen load delivered to the estuaries.
      Point sources account for 28% while atmospheric deposition accounts for 20%. A
      second SPARROW model was used to examine the sources and delivery of phosphorus
      to lakes and reservoirs throughout the NE US. The greatest attenuation of
      phosphorus occurred in lakes that were large relative to the size of their
      watershed. Model results show that, within the NE US, aquatic decay of nutrients
      is quite limited on an annual basis and that we especially cannot rely on natural
      attenuation to remove nutrients within the larger rivers nor within lakes with
      large watersheds relative to the size of the lake.

PMID- 22457579
TI  - A Regional Modeling Framework of Phosphorus Sources and Transport in Streams of
      the Southeastern United States.
AB  - We applied the SPARROW model to estimate phosphorus transport from catchments to
      stream reaches and subsequent delivery to major receiving water bodies in the
      Southeastern United States (U.S.). We show that six source variables and five
      land-to-water transport variables are significant (p<0.05) in explaining 67% of
      the variability in long-term log-transformed mean annual phosphorus yields. Three
      land-to-water variables are a subset of landscape characteristics that have been
      used as transport factors in phosphorus indices developed by state agencies and
      are identified through experimental research as influencing land-to-water
      phosphorus transport at field and plot scales. Two land-to-water variables - soil
      organic matter and soil pH - are associated with phosphorus sorption, a
      significant finding given that most state-developed phosphorus indices do not
      explicitly contain variables for sorption processes. Our findings for
      Southeastern U.S. streams emphasize the importance of accounting for phosphorus
      present in the soil profile to predict attainable instream water quality.
      Regional estimates of phosphorus associated with soil-parent rock were highly
      significant in explaining instream phosphorus yield variability. Model
      predictions associate 31% of phosphorus delivered to receiving water bodies to
      geology and the highest total phosphorus yields in the Southeast were catchments
      with already high background levels that have been impacted by human activity.

PMID- 22457580
TI  - Nutrient Inputs to the Laurentian Great Lakes by Source and Watershed Estimated
      Using SPARROW Watershed Models.
AB  - Nutrient input to the Laurentian Great Lakes continues to cause problems with
      eutrophication. To reduce the extent and severity of these problems, target
      nutrient loads were established and Total Maximum Daily Loads are being developed
      for many tributaries. Without detailed loading information it is difficult to
      determine if the targets are being met and how to prioritize rehabilitation
      efforts. To help address these issues, SPAtially Referenced Regressions On
      Watershed attributes (SPARROW) models were developed for estimating loads and
      sources of phosphorus (P) and nitrogen (N) from the United States (U.S.) portion
      of the Great Lakes, Upper Mississippi, Ohio, and Red River Basins. Results
      indicated that recent U.S. loadings to Lakes Michigan and Ontario are similar to
      those in the 1980s, whereas loadings to Lakes Superior, Huron, and Erie
      decreased. Highest loads were from tributaries with the largest watersheds,
      whereas highest yields were from areas with intense agriculture and large point
      sources of nutrients. Tributaries were ranked based on their relative loads and
      yields to each lake. Input from agricultural areas was a significant source of
      nutrients, contributing ~33-44% of the P and ~33-58% of the N, except for areas
      around Superior with little agriculture. Point sources were also significant,
      contributing ~14-44% of the P and 13-34% of the N. Watersheds around Lake Erie
      contributed nutrients at the highest rate (similar to intensively farmed areas in
      the Midwest) because they have the largest nutrient inputs and highest delivery
      ratio.

PMID- 22457581
TI  - Nutrient Sources and Transport in the Missouri River Basin, with Emphasis on the
      Effects of Irrigation and Reservoirs.
AB  - SPAtially Referenced Regressions On Watershed attributes (SPARROW) models were
      used to relate instream nutrient loads to sources and factors influencing the
      transport of nutrients in the Missouri River Basin. Agricultural inputs from
      fertilizer and manure were the largest nutrient sources throughout a large part
      of the basin, although atmospheric and urban inputs were important sources in
      some areas. Sediment mobilized from stream channels was a source of phosphorus in
      medium and larger streams. Irrigation on agricultural land was estimated to
      decrease the nitrogen load reaching the Mississippi River by as much as 17%,
      likely as a result of increased anoxia and denitrification in the soil zone.
      Approximately 16% of the nitrogen load and 33% of the phosphorus load that would
      have otherwise reached the Mississippi River was retained in reservoirs and lakes
      throughout the basin. Nearly half of the total attenuation occurred in the eight
      largest water bodies. Unlike the other major tributary basins, nearly the entire
      instream nutrient load leaving the outlet of the Platte and Kansas River
      subbasins reached the Mississippi River. Most of the larger reservoirs and lakes
      in the Platte River subbasin are upstream of the major sources, whereas in the
      Kansas River subbasin, most of the source inputs are in the southeast part of the
      subbasin where characteristics of the area and proximity to the Missouri River
      facilitate delivery of nutrients to the Mississippi River.

PMID- 22457582
TI  - Sources and Delivery of Nutrients to the Northwestern Gulf of Mexico from Streams
      in the South-Central United States.
AB  - SPAtially Referenced Regressions On Watershed attributes (SPARROW) models were
      developed to estimate nutrient inputs [total nitrogen (TN) and total phosphorus
      (TP)] to the northwestern part of the Gulf of Mexico from streams in the South
      Central United States (U.S.). This area included drainages of the Lower
      Mississippi, Arkansas-White-Red, and Texas-Gulf hydrologic regions. The models
      were standardized to reflect nutrient sources and stream conditions during 2002.
      Model predictions of nutrient loads (mass per time) and yields (mass per area per
      time) generally were greatest in streams in the eastern part of the region and
      along reaches near the Texas and Louisiana shoreline. The Mississippi River and
      Atchafalaya River watersheds, which drain nearly two-thirds of the conterminous
      U.S., delivered the largest nutrient loads to the Gulf of Mexico, as expected.
      However, the three largest delivered TN yields were from the Trinity
      River/Galveston Bay, Calcasieu River, and Aransas River watersheds, while the
      three largest delivered TP yields were from the Calcasieu River, Mermentau River,
      and Trinity River/Galveston Bay watersheds. Model output indicated that the three
      largest sources of nitrogen from the region were atmospheric deposition (42%),
      commercial fertilizer (20%), and livestock manure (unconfined, 17%). The three
      largest sources of phosphorus were commercial fertilizer (28%), urban runoff
      (23%), and livestock manure (confined and unconfined, 23%).

PMID- 22457583
TI  - Modeled Sources, Transport, and Accumulation of Dissolved Solids in Water
      Resources of the Southwestern United States.
AB  - Information on important source areas for dissolved solids in streams of the
      southwestern United States, the relative share of deliveries of dissolved solids
      to streams from natural and human sources, and the potential for salt
      accumulation in soil or groundwater was developed using a SPAtially Referenced
      Regressions On Watershed attributes model. Predicted area-normalized reach
      catchment delivery rates of dissolved solids to streams ranged from <10
      (kg/year)/km(2) for catchments with little or no natural or human-related solute
      sources in them to 563,000 (kg/year)/km(2) for catchments that were almost
      entirely cultivated land. For the region as a whole, geologic units contributed
      44% of the dissolved-solids deliveries to streams and the remaining 56% of the
      deliveries came from the release of solutes through irrigation of cultivated and
      pasture lands, which comprise only 2.5% of the land area. Dissolved-solids
      accumulation is manifested as precipitated salts in the soil or underlying
      sediments, and (or) dissolved salts in soil-pore or sediment-pore water, or
      groundwater, and therefore represents a potential for aquifer contamination.
      Accumulation rates were <10,000 (kg/year)/km(2) for many hydrologic accounting
      units (large river basins), but were more than 40,000 (kg/year)/km(2) for the
      Middle Gila, Lower Gila-Agua Fria, Lower Gila, Lower Bear, Great Salt Lake
      accounting units, and 247,000 (kg/year)/km(2) for the Salton Sea accounting unit.

PMID- 22457584
TI  - Surface-Water Nutrient Conditions and Sources in the United States Pacific
      Northwest.
AB  - The SPAtially Referenced Regressions On Watershed attributes (SPARROW) model was
      used to perform an assessment of surface-water nutrient conditions and to
      identify important nutrient sources in watersheds of the Pacific Northwest region
      of the United States (U.S.) for the year 2002. Our models included variables
      representing nutrient sources as well as landscape characteristics that affect
      nutrient delivery to streams. Annual nutrient yields were higher in watersheds on
      the wetter, west side of the Cascade Range compared to watersheds on the drier,
      east side. High nutrient enrichment (relative to the U.S. Environmental
      Protection Agency's recommended nutrient criteria) was estimated in watersheds
      throughout the region. Forest land was generally the largest source of total
      nitrogen stream load and geologic material was generally the largest source of
      total phosphorus stream load generated within the 12,039 modeled watersheds.
      These results reflected the prevalence of these two natural sources and the low
      input from other nutrient sources across the region. However, the combined input
      from agriculture, point sources, and developed land, rather than natural nutrient
      sources, was responsible for most of the nutrient load discharged from many of
      the largest watersheds. Our results provided an understanding of the regional
      patterns in surface-water nutrient conditions and should be useful to
      environmental managers in future water-quality planning efforts.

PMID- 22457585
TI  - A Web-Based Decision Support System for Assessing Regional Water-Quality
      Conditions and Management Actions.
AB  - The U.S. Geological Survey National Water Quality Assessment Program has
      completed a number of water-quality prediction models for nitrogen and phosphorus
      for the conterminous United States as well as for regional areas of the nation.
      In addition to estimating water-quality conditions at unmonitored streams, the
      calibrated SPAtially Referenced Regressions On Watershed attributes (SPARROW)
      models can be used to produce estimates of yield, flow-weighted concentration, or
      load of constituents in water under various land-use condition, change, or
      resource management scenarios. A web-based decision support infrastructure has
      been developed to provide access to SPARROW simulation results on stream water
      quality conditions and to offer sophisticated scenario testing capabilities for
      research and water-quality planning via a graphical user interface with familiar
      controls. The SPARROW decision support system (DSS) is delivered through a web
      browser over an Internet connection, making it widely accessible to the public in
      a format that allows users to easily display water-quality conditions and to
      describe, test, and share modeled scenarios of future conditions. SPARROW models
      currently supported by the DSS are based on the modified digital versions of the
      1:500,000-scale River Reach File (RF1) and 1:100,000-scale National Hydrography
      Dataset (medium-resolution, NHDPlus) stream networks.

PMID- 22457586
TI  - The Regionalization of National-Scale SPARROW Models for Stream Nutrients.
AB  - This analysis modifies the parsimonious specification of recently published total
      nitrogen (TN) and total phosphorus (TP) national-scale SPAtially Referenced
      Regressions On Watershed attributes models to allow each model coefficient to
      vary geographically among three major river basins of the conterminous United
      States. Regionalization of the national models reduces the standard errors in the
      prediction of TN and TP loads, expressed as a percentage of the predicted load,
      by about 6 and 7%. We develop and apply a method for combining national-scale and
      regional-scale information to estimate a hybrid model that imposes cross-region
      constraints that limit regional variation in model coefficients, effectively
      reducing the number of free model parameters as compared to a collection of
      independent regional models. The hybrid TN and TP regional models have improved
      model fit relative to the respective national models, reducing the standard error
      in the prediction of loads, expressed as a percentage of load, by about 5 and 4%.
      Only 19% of the TN hybrid model coefficients and just 2% of the TP hybrid model
      coefficients show evidence of substantial regional specificity (more than +/-100%
      deviation from the national model estimate). The hybrid models have much greater
      precision in the estimated coefficients than do the unconstrained regional
      models, demonstrating the efficacy of pooling information across regions to
      improve regional models.

PMID- 22457587
TI  - Retinal toxicity to antimalarial drugs: chloroquine and hydroxychloroquine: a
      neurophysiologic study.
AB  - Over a 30-year period, 29 cases of antimalarial retinal toxicity were studied in
      a tertiary medical center. Three cases of chloroquine and 26 cases of
      hydroxychloroquine toxicity were studied. A number of these cases were studied
      before multifocal electroretinogram (mfERG) became available and show how
      insensitive the corneal full-field flash ERG is in diagnosing this condition. It
      became apparent that even mfERG failed to diagnose some early patients who either
      had an abnormal fundus examination or Humphrey's automated perimetry (protocol 10
      2). The age of the patient and the number of years of exposure to antimalarial
      drugs appears to be directly related to the development of this retinal disorder.
      All three of the "quantitative retinal tests" recommended in the "Guidelines" -
      mfERG, spectral domain optical coherence tomography (SD-OCT), and
      autofluorescence - fail to identify all of the cases of antimalarial retinal
      toxicity. mfERG is probably the most sensitive of the three tests, but no direct
      comparison has yet been accomplished. None of these "quantitative tests" appear
      to provide the "gold standard" necessary for detecting early hydroxychloroquine
      retinal toxicity.

PMID- 22457588
TI  - Pneumatic tools for vitreoretinal surgery.
AB  - One of the difficulties of microsurgery is learning how to control physiological
      tremors. The pneumatic tool eliminates the physiological tremor, but no tactile
      feedback is provided. The manual tremor when closing the forceps is completely
      eliminated and the exact target can be more easily grabbed. Forceps closure
      pressure can rise up to 50 psi, whereas the scissors can be used in two modes:
      multicut and proportional. When performing bimanual surgery the pedal range is
      divided into two steps: in the first step, the forceps are controlled, and in the
      second step, the forceps remain closed. At the same time the scissors start to
      work in the preselected mode. No adverse events occurred and no iatrogenic
      retinal breaks were produced. Precision and control sensation were a grateful
      surprise.

PMID- 22457589
TI  - Optic neuritis in a child with biotinidase deficiency: case report and literature
      review.
AB  - Optic atrophy has often been reported in children with biotinidase deficiency.
      The visual prognosis is usually poor. This report is of a 6-year-old boy with an
      early onset of biotinidase deficiency who presented with acute profound visual
      loss in both eyes. Fundoscopy revealed swollen discs in both eyes, and the
      imaging was consistent with bilateral optic neuritis. He was treated with
      systemic corticosteroid, and commenced on oral biotin. The final visual outcome
      was promising.

PMID- 22457590
TI  - An evaluation of the accuracy of the ORange (Gen II) by comparing it to the
      IOLMaster in the prediction of postoperative refraction.
AB  - PURPOSE: The aim of this study was to evaluate the accuracy of ORange((r)) Gen II
      (WaveTec Vision, Aliso Viejo, CA). SETTING: The Surgical Suites, Honolulu, HI.
      METHODS: The prospective 28 consecutive cataract surgical cases were selected
      from 85 cataract surgical cases between December 16, 2010 and February 24, 2011.
      With the same intraocular lens implantation, the predicted spherical equivalent
      refraction from IOLMaster((r)) (Carl Zeiss AG, Oberkochen, Germany) and ORange
      Gen II were statistically compared and verified with 1-month postoperative
      manifest refraction. The data were put into IBM SPSS 19 (SPSS Inc, Chicago, IL)
      for analysis of variance. Pearson's correlation coefficient was also calculated
      to evaluate the correlation between the IOLMaster, ORange Gen II, and 1-month
      postoperative manifest refraction. RESULTS: There were no statistically
      significant differences in the mean spherical equivalent refraction from the
      IOLMaster, ORange Gen II, and 1-month postoperative manifest refraction
      (IOLMaster -0.40 diopters, P = 0.07; ORange Gen II -0.43 diopters, P = 0.16; 1
      month refraction -0.41 diopters, P = 0.07). Pearson's correlation study
      demonstrated that all three were positively correlated (P < 0.05), with the
      strongest correlation between the ORange Gen II and 1-month postoperative
      manifest refraction (r = +0.6, P < 0.01). CONCLUSION: The ORange Gen II can be
      considered as an alternative method for intraocular lens selection for cataract
      patients.

PMID- 22457591
TI  - Degradable biocomposite of nano calcium-deficient hydroxyapatite-multi(amino
      acid) copolymer.
AB  - BACKGROUND AND METHODS: A nano calcium-deficient hydroxyapatite (n-CDHA)
      multi(amino acid) copolymer (MAC) composite bone substitute biomaterial was
      prepared using an in situ polymerization method. The composition, structure, and
      compressive strength of the composite was characterized, and the in vitro
      degradability in phosphate-buffered solution and preliminary cell responses to
      the composite were investigated. RESULTS: The composite comprised n-CDHA and an
      amide linkage copolymer. The compressive strength of the composite was in the
      range of 88-129 MPa, varying with the amount of n-CDHA in the MAC (ranging from
      10 wt% to 50 wt%). Weight loss from the composite increased (from 32.2 wt% to
      44.3 wt%) with increasing n-CDHA content (from 10 wt% to 40 wt%) in the MAC after
      the composite was soaked in phosphate-buffered solution for 12 weeks. The pH of
      the soaking medium varied from 6.9 to 7.5. MG-63 cells with an osteogenic
      phenotype were well adhered and spread on the composite surface. Viability and
      differentiation increased with time, indicating that the composite had no
      negative effects on MG-63 cells. CONCLUSION: The n-CDHA-MAC composite had good
      cytocompatibility and has potential to be used as a bone substitute.

PMID- 22457592
TI  - Delivery of a transforming growth factor beta-1 plasmid to mesenchymal stem cells
      via cationized Pleurotus eryngii polysaccharide nanoparticles.
AB  - The objective of this study was to investigate the use of cationized Pleurotus
      eryngii polysaccharide (CPEPS) as a nonviral gene delivery vehicle to transfer
      plasmid DNA encoding transforming growth factor beta-1 (pTGF-beta1) into
      mesenchymal stem cells (MSCs) in vitro. Crude P. eryngii polysaccharide was
      purified, and then cationized by grafting spermine onto the backbone of the
      polysaccharide. Agarose gel electrophoresis, transmission electron microscopy,
      and a Nano Sense Zetasizer (Malvern Instruments, Malvern, UK) were used to
      characterize the CPEPS-pTGF-beta1 nanoparticles. The findings of cytotoxicity
      analysis showed that when the nanoparticles were formulated with a CPEPS/pTGF
      beta1 weight ratio >= 10:1, a greater gel retardation effect was observed during
      agarose gel electrophoresis. The CPEPS-pTGF-beta1 nanoparticles with a weight
      ratio of 20:1, respectively, possessed an average particle size of 80.8 nm in
      diameter and a zeta potential of +17.4 +/- 0.1 mV. Significantly, these CPEPS
      pTGF-beta1 nanoparticles showed lower cytotoxicity and higher transfection
      efficiency than both polyethylenimine (25 kDa) (P = 0.006, Student's t-test) and
      Lipofectamine(TM) 2000 (P = 0.002, Student's t-test). Additionally, the messenger
      RNA expression level of TGF-beta1 in MSCs transfected with CPEPS-pTGF-beta1
      nanoparticles was significantly higher than that of free plasmid DNA-transfected
      MSCs and slightly elevated compared with that of Lipofectamine 2000-transfected
      MSCs. Flow cytometry analysis demonstrated that 92.38% of MSCs were arrested in
      the G1 phase after being transfected with CPEPS-pTGF-beta1 nanoparticles,
      indicating a tendency toward differentiation. In summary, the findings of this
      study suggest that the CPEPS-pTGF-beta1 nanoparticles prepared in this work
      exhibited excellent transfection efficiency and low toxicity. Therefore, they
      could be developed into a promising nonviral vector for gene delivery in vitro.

PMID- 22457593
TI  - Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in
      allergic airway inflammation.
AB  - The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a
      murine model of asthma in a previous study. But more specific mechanisms of
      silver NPs in an attenuation of allergic airway inflammation have not yet been
      established. Vascular and mucous changes are believed to contribute largely in
      pathophysiology in asthma. Among various factors related to vascular changes,
      vascular endothelial growth factor (VEGF) plays a pivotal role in vascular
      changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as
      markers of goblet cell metaplasia in lung pathologies. The aim of this study was
      to investigate the effects of silver NPs on VEGF signaling pathways and mucus
      hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate
      the role of silver NPs and the related molecular mechanisms in allergic airway
      disease. In this study, with an OVA-induced murine model of allergic airway
      disease, it was found that the increased levels of hypoxia-inducible factor (HIF)
      1alpha, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels,
      and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially
      decreased by the administration of silver NPs. In summary, silver NPs
      substantially suppressed mucus hypersecretion and PI3K/HIF-1alpha/VEGF signaling
      pathway in an allergic airway inflammation.

PMID- 22457594
TI  - Role of hydroxypropyl-beta-cyclodextrin on freeze-dried and gamma-irradiated PLGA
      and PLGA-PEG diblock copolymer nanospheres for ophthalmic flurbiprofen delivery.
AB  - Poly(D,L-lactide-co-glycolide) and poly(D,L-lactide-co-glycolide) with
      poly(ethylene glycol) nanospheres (NSs) incorporating flurbiprofen (FB) were
      freeze-dried with several cryoprotective agents and sterilized by gamma
      irradiation. Only when 5.0% (w/v) hydroxypropyl-beta-cyclodextrin (HPbetaCD) was
      used, a complete resuspension by manual shaking and almost identical particle
      size of the NSs was obtained after freeze-drying. In vitro drug release and ex
      vivo corneal permeation of NSs with and without HPbetaCD were evaluated. The
      presence of HPbetaCD resulted in a reduction of burst effect, providing a more
      sustained release of the drug. A significant decrease in the FB transcorneal
      permeation of NSs containing HPbetaCD was obtained, related to the slower
      diffusion of FB observed in the in vitro results. The uptake mechanism of the NSs
      was examined by confocal microscopy, suggesting that NSs penetrate corneal
      epithelium through a transcellular pathway. Ocular tolerance was assessed in
      vitro and in vivo by the EytexTM and Draize test, respectively. Long-term
      stability studies revealed that gamma-irradiated NSs stored as freeze-dried
      powders maintained their initial characteristics. Stability studies of the
      resuspended NSs after 3 months of storage in the aqueous form showed that NSs
      were stable at 4 degrees C, while formulations stored at 25 degrees C and 40
      degrees C increased their initial particle size.

PMID- 22457595
TI  - Increased brain radioactivity by intranasal P-labeled siRNA dendriplexes within
      in situ-forming mucoadhesive gels.
AB  - BACKGROUND: Molecules taken up by olfactory and trigeminal nerve neurons directly
      access the brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels
      would increase the residence time of intranasal material, favoring the nose-to
      brain delivery. In this first approach, brain radioactivity after intranasal
      administration of (32)P-small interference RNA (siRNA) complexed with
      poly(amidoamine) G7 dendrimers (siRNA dendriplexes) within in situ-forming
      mucoadhesive gels, was determined. MATERIALS: (32)P-siRNA dendriplexes were
      incorporated into in situ-forming mucoadhesive gels prepared by blending
      thermosensitive poloxamer (23% w/w) with mucoadhesive chitosan (1% w/w, PxChi) or
      carbopol (0.25% w/w, PxBCP). Rheological properties, radiolabel release profile,
      and local toxicity in rat nasal mucosa were determined. The best-suited
      formulation was intranasally administered to rats, and blood absorption and brain
      distribution of radioactivity were measured. RESULTS: The gelation temperature of
      both formulations was 23 degrees C. The PxChi liquid showed non-Newtonian
      pseudoplastic behavior of high consistency and difficult manipulation, and the
      gel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a
      Newtonian behavior of low viscosity and easy manipulation, while in the gel phase
      showed apparent viscosity similar to that of the mucus but higher than that of
      aqueous solution. The gel released 35% of radiolabel and the released material
      showed silencing activity in vitro. Three intranasal doses of dendriplexes in
      PxCBP gel did not damage the rat nasal mucosa. A combination of (32)P-siRNA
      complexation with dendrimers, incorporation of the dendriplexes into PxCBP gel,
      and administration of two intranasal doses was necessary to achieve higher brain
      radioactivity than that achieved by intravenous dendriplexes or intranasal naked
      siRNA. CONCLUSION: The increased radioactivity within the olfactory bulb
      suggested that the combination above mentioned favored the mediation of a direct
      brain delivery.

PMID- 22457596
TI  - Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced
      inflammatory response in human monocytes.
AB  - BACKGROUND: Cerium dioxide (CeO(2)) nanoparticles have potential therapeutic
      applications and are widely used for industrial purposes. However, the effects of
      these nanoparticles on primary human cells are largely unknown. The ability of
      nanoparticles to exacerbate pre-existing inflammatory disorders is not well
      documented for engineered nanoparticles, and is certainly lacking for CeO(2)
      nanoparticles. We investigated the inflammation-modulating effects of CeO(2)
      nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes.
      METHODS: CD14(+) cells were isolated from peripheral blood samples of human
      volunteers. Cells were exposed to either 0.5 or 1 MUg/mL of CeO(2) nanoparticles
      over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL)
      prestimulation. Modulation of the inflammatory response was studied by measuring
      secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic
      protein-1, interferon-gamma, and interferon gamma-induced protein 10. RESULTS:
      CeO(2) nanoparticle suspensions were thoroughly characterized using dynamic light
      scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (-14
      mV), and transmission electron microscopy (irregular-shaped particles).
      Transmission electron microscopy of CD14(+) cells exposed to CeO(2) nanoparticles
      revealed that these nanoparticles were efficiently internalized by monocytes and
      were found either in vesicles or free in the cytoplasm. However, no significant
      differences in secreted cytokine profiles were observed between CeO(2)
      nanoparticle-treated cells and control cells at noncytotoxic doses. No
      significant effects of CeO(2) nanoparticle exposure subsequent to
      lipopolysaccharide priming was observed on cytokine secretion. Moreover, no
      significant difference in lipopolysaccharide-induced cytokine production was
      observed after exposure to CeO(2) nanoparticles followed by lipopolysaccharide
      exposure. CONCLUSION: CeO(2) nanoparticles at noncytotoxic concentrations neither
      modulate pre-existing inflammation nor prime for subsequent exposure to
      lipopolysaccharides in human monocytes from healthy subjects.

PMID- 22457598
TI  - A scalable fabrication process of polymer microneedles.
AB  - While polymer microneedles may easily be fabricated by casting a solution in a
      mold, either centrifugation or vacuumizing is needed to pull the viscous polymer
      solution into the microholes of the mold. We report a novel process to fabricate
      polymer microneedles with a one-sided vacuum using a ceramic mold that is
      breathable but water impermeable. A polymer solution containing polyvinyl alcohol
      and polysaccharide was cast in a ceramic mold and then pulled into the microholes
      by a vacuum applied to the opposite side of the mold. After cross-linking and
      solidification through freeze-thawing, the microneedle patch was detached from
      the mold and transferred with a specially designed instrument for the drying
      process, during which the patch shrank evenly to form an array of regular and
      uniform needles without deformation. Moreover, the shrinkage of the patches
      helped to reduce the needles' size to ease microfabrication of the male mold. The
      dried microneedle patches were finally punched to the desired sizes to achieve
      various properties, including sufficient strength to penetrate skin, microneedles
      absorbed water-swelling ratios, and drug-release kinetics. The results showed
      that the microneedles were strong enough to penetrate pigskin and that their
      performance was satisfactory in terms of swelling and drug release.

PMID- 22457597
TI  - Low molecular weight chitosan nanoparticulate system at low N:P ratio for
      nontoxic polynucleotide delivery.
AB  - Chitosan, a natural polymer, is a promising system for the therapeutic delivery
      of both plasmid DNA and synthetic small interfering RNA. Reports attempting to
      identify the optimal parameters of chitosan for synthetic small interfering RNA
      delivery were inconclusive with high molecular weight at high amine-to-phosphate
      (N:P) ratios apparently required for efficient transfection. Here we show, for
      the first time, that low molecular weight chitosan (LMW-CS) formulations at low
      N:P ratios are suitable for the in vitro delivery of small interfering RNA. LMW
      CS nanoparticles at low N:P ratios were positively charged (zeta-potential ~20
      mV) with an average size below 100 nm as demonstrated by dynamic light scattering
      and environmental scanning electron microscopy, respectively. Nanoparticles were
      spherical, a shape promoting decreased cytotoxicity and enhanced cellular uptake.
      Nanoparticle stability was effective for at least 20 hours at N:P ratios above
      two in a slightly acidic pH of 6.5. At a higher basic pH of 8, these
      nanoparticles were unravelled due to chitosan neutralization, exposing their
      polynucleotide cargo. Cellular uptake ranged from 50% to 95% in six different
      cell lines as measured by cytometry. Increasing chitosan molecular weight
      improved nanoparticle stability as well as the ability of nanoparticles to
      protect the oligonucleotide cargo from nucleases at supraphysiological
      concentrations. The highest knockdown efficiency was obtained with the specific
      formulation 92-10-5 that combines sufficient nuclease protection with effective
      intracellular release. This system attained >70% knockdown of the messenger RNA,
      similar to commercially available lipoplexes, without apparent cytotoxicity.
      Contrary to previous reports, our data demonstrate that LMW-CS at low N:P ratios
      are efficient and nontoxic polynucleotide delivery systems capable of
      transfecting a plethora of cell lines.

PMID- 22457599
TI  - Update on non-bismuth quadruple (concomitant) therapy for eradication of
      Helicobacter pylori.
AB  - BACKGROUND: Traditional standard triple therapy for Helicobacter pylori (H.
      pylori) infection (proton pump inhibitor-clarithromycin-amoxicillin) can easily
      be converted to non-bismuth quadruple (concomitant) therapy by the addition of a
      nitroimidazole twice daily. AIM: To critically review evidence on the role of non
      bismuth quadruple therapy (proton pump inhibitor-clarithromycin-amoxicillin
      nitroimidazole) in the treatment of H. pylori infection. METHODS: Bibliographical
      searches were performed in MEDLINE and relevant congresses up to December 2011.
      We performed a meta-analysis of the studies evaluating the concomitant therapy,
      and of the randomized controlled trials comparing the concomitant and the
      standard triple therapy. RESULTS: A meta-analysis of 19 studies (2070 patients)
      revealed a mean H. pylori cure rate (intention-to-treat) of 88% (95% confidence
      interval from 85% to 91%) for non-bismuth quadruple therapy. We performed a meta
      analysis of the randomized controlled studies comparing the concomitant (481
      patients) and the standard triple therapy (503 patients). The former was more
      effective than the latter: 90% versus 78% (intention-to-treat analysis). Results
      were homogeneous (I(2) = 0%). The odds ratio for this comparison was 2.36 (95%
      confidence interval from 1.67 to 3.34). A tendency toward better results with
      longer treatments (7-10 days versus 3-5 days) has been observed, so it seems
      reasonable to recommend the length of treatment achieving the highest cure rates
      (10 days). Clarithromycin resistance may reduce the efficacy of non-bismuth
      quadruple therapy, although the decrease in eradication rates seems to be far
      lower than in standard triple therapy. Experience with the non-bismuth quadruple
      therapy in patients with metronidazole-resistant strains is still very limited.
      CONCLUSION: Non-bismuth quadruple (concomitant) therapy appears to be an
      effective, safe, and well-tolerated alternative to triple therapy and is less
      complex than sequential therapy. Therefore, this regimen appears well suited for
      use in settings where the efficacy of triple therapy is unacceptably low.

PMID- 22457600
TI  - Current and future options for the management of phantom-limb pain.
AB  - Phantom-limb pain (PLP) belongs among difficult-to-treat chronic pain syndromes.
      Treatment options for PLP are to a large degree implicated by the level of
      understanding the mechanisms and nature of PLP. Research and clinical findings
      acknowledge the neuropathic nature of PLP and also suggest that both peripheral
      as well as central mechanisms, including neuroplastic changes in central nervous
      system, can contribute to PLP. Neuroimaging studies in PLP have indicated a
      relation between PLP and the neuroplastic changes. Further, it has been shown
      that the pathological neuroplastic changes could be reverted, and there is a
      parallel between an improvement (reversal) of the neuroplastic changes in PLP and
      pain relief. These findings facilitated explorations of novel neuromodulatory
      treatment strategies, adding to the variety of treatment approaches in PLP.
      Overall, available treatment options in PLP include pharmacological treatment,
      supportive non-pharmacological non-invasive strategies (eg, neuromodulation using
      transcranial magnetic stimulation, visual feedback therapy, or motor imagery;
      peripheral transcutaneous electrical nerve stimulation, physical therapy,
      reflexology, or various psychotherapeutic approaches), and invasive treatment
      strategies (eg, surgical destructive procedures, nerve blocks, or invasive
      neuromodulation using deep brain stimulation, motor cortex stimulation, or spinal
      cord stimulation). Venues of further development in PLP management include a
      technological and methodological improvement of existing treatment methods, an
      implementation of new techniques and products, and a development of new treatment
      approaches.

PMID- 22457601
TI  - New treatment options in the management of hypertension: appraising the potential
      role of azilsartan medoxomil.
AB  - Renin-angiotensin-system (RAS) activation plays a key role in the development of
      hypertension and cardiovascular disease. Drugs that antagonize the RAS
      (angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers
      [ARBs]) have proven clinical efficacy in reducing blood pressure values and
      cardiovascular morbidity and mortality. ACE inhibitors partially inhibit plasma
      ACE, and angiotensin II generation. Thus, ARBs, which block selectively type 1
      angiotensin II receptor (AT(1)R), have been developed and used in the clinical
      management of hypertension and cardiovascular disease. Experimental and clinical
      trials with ARBs indicate that this class of drug represents an effective, safe
      and well tolerated therapeutic option for the prevention and care of
      hypertension, even though there is no proven superiority as compared to ACE
      inhibitors except for the better tolerability. Most ARBs may not completely
      inhibit the AT(1)R at the approved clinical doses. Azilsartan medoxomil is a
      newly approved ARB for the management of hypertension. This ARB induces a potent
      and long-lasting antihypertensive effect and may have cardioprotective
      properties. This article reviews the current evidence on the clinical
      effectiveness of azilsartan in hypertension.

PMID- 22457603
TI  - Bevacizumab for the treatment of nonsquamous non-small-cell lung cancer in
      Portugal: a retrospective, multicenter study.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer-related mortality. In
      patients with nonsquamous non-small-cell lung cancer (NSCLC) stage IIIB/IV
      treatment with chemotherapy plus bevacizumab led to significant improvements in
      progression-free and median overall survival (OS). AIM: To report the experience
      of five Portuguese centers in treating patients with nonsquamous NSCLC in stage
      IIIB or IV with bevacizumab and chemotherapy regarding survival and toxicity
      outcomes. MATERIALS AND METHODS: This was a retrospective, multicenter study on
      patients with nonsquamous stage IIIB/IV NSCLC treated with bevacizumab and
      chemotherapy from November 2007 to August 2010 through special use permits. We
      reviewed the medical records, registry of demographic characteristics, treatments
      provided, treatment responses, adverse events, and dates of death. Statistical
      analysis was performed with SPSS statistics software. Median OS and event-free
      survival (EFS) were calculated using the Kaplan-Meier method. RESULTS: From an
      eligible population of 41 patients, 37 participants were registered. Study
      participants were predominantly male (78.4%) with a median age of 53 years (29-75
      years). In total, 83.8% patients had stage IV disease (TNM, 6th Ed.). The OS was
      21.5 months (95% confidence interval [CI]: 12.6-30.5] and median EFS was 9.4
      months (95% CI9: 7.1-11.7). Hematologic toxicity grade 3/4 occurred in 35.1% of
      patients, and nonhematologic toxicity in 24.3% patients. One fatal thromboembolic
      event was recorded (2.7%). CONCLUSIONS: The results of chemotherapy plus
      bevacizumab treatment for nonsquamous NSCLC obtained from the daily clinical
      practice of the centers involved in this study were similar to those of published
      clinical trials. Collaboration between the different Portuguese centers is
      crucial for this kind of study.

PMID- 22457602
TI  - Management of cutaneous T cell lymphoma: new and emerging targets and treatment
      options.
AB  - Cutaneous T cell lymphomas (CTCL) clinically and biologically represent a
      heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sezary
      syndrome being the most common subtypes. Over the last decade, new immunological
      and molecular pathways have been identified that not only influence CTCL
      phenotype and growth, but also provide targets for therapies and prognostication.
      This review will focus on recent advances in the development of therapeutic
      agents, including bortezomib, the histone deacetylase inhibitors (vorinostat and
      romidepsin), and pralatrexate in CTCL.

PMID- 22457604
TI  - A comparative study of mammalian diversification pattern.
AB  - Although mammals have long been regarded as a successful radiation, the
      diversification pattern among the clades is still poorly known. Higher-level
      phylogenies are conflicting and comprehensive comparative analyses are still
      lacking. Using a recently published supermatrix encompassing nearly all extant
      mammalian families and a novel comparative likelihood approach (MEDUSA), the
      diversification pattern of mammalian groups was examined. Both order- and family
      level phylogenetic analyses revealed the rapid radiation of Boreoeutheria and
      Euaustralidelphia in the early mammalian history. The observation of a
      diversification burst within Boreoeutheria at approximately 100 My supports the
      Long Fuse model in elucidating placental diversification progress, and the rapid
      radiation of Euaustralidelphia suggests an important role of biogeographic
      dispersal events in triggering early Australian marsupial rapid radiation.
      Diversification analyses based on family-level diversity tree revealed seven
      additional clades with exceptional diversification rate shifts, six of which
      represent accelerations in net diversification rate as compared to the background
      pattern. The shifts gave origin to the clades Muridae+Cricetidae,
      Bovidae+Moschidae+Cervidae, Simiiformes, Echimyidae, Odontoceti (excluding
      Physeteridae+Kogiidae+Platanistidae), Macropodidae, and Vespertilionidae.
      Moderate to high extinction rates from background and boreoeutherian
      diversification patterns indicate the important role of turnovers in shaping the
      heterogeneous taxonomic richness observed among extant mammalian groups.
      Furthermore, the present results emphasize the key role of extinction on erasing
      unusual diversification signals, and suggest that further studies are needed to
      clarify the historical radiation of some mammalian groups for which MEDUSA did
      not detect exceptional diversification rates.

PMID- 22457605
TI  - Characterization of bovine induced pluripotent stem cells by lentiviral
      transduction of reprogramming factor fusion proteins.
AB  - Pluripotent stem cells from domesticated animals have potential applications in
      transgenic breeding. Here, we describe induced pluripotent stem (iPS) cells
      derived from bovine fetal fibroblasts by lentiviral transduction of Oct4, Sox2,
      Klf4 and c-Myc defined-factor fusion proteins. Bovine iPS cells showed typical
      colony morphology, normal karyotypes, stained positively for alkaline phosphatase
      (AP) and expressed Oct4, Nanog and SSEA1. The CpG in the promoter regions of Oct4
      and Nanog were highly unmethylated in bovine iPS cells compared to the
      fibroblasts. The cells were able to differentiate into cell types of all three
      germ layers in vitro and in vivo. In addition, these cells were induced into
      female germ cells under defined culture conditions and expressed early and late
      female germ cell-specific genes Vasa, Dazl, Gdf9, Nobox, Zp2, and Zp3. Our data
      suggest that bovine iPS cells were generated from bovine fetal fibroblasts with
      defined-factor fusion proteins mediated by lentivirus and have potential
      applications in bovine transgenic breeding and gene-modified animals.

PMID- 22457606
TI  - Propolis standardized extract (EPP-AF(r)), an innovative chemically and
      biologically reproducible pharmaceutical compound for treating wounds.
AB  - The aim of this study was to develop a formulation, containing the propolis
      standardized extract (EPP-AF((r))), which can assist in the healing of skin
      lesions. To achieve this objective the antimicrobial activity and chemical
      composition of the propolis extract was determined. The final product was
      subjected to in vitro and in vivo pre-clinical evaluation. The broth
      macrodilution method was used to determine the antimicrobial activity of the
      extracts and formulations against the microorganisms most commonly found in
      burns, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli,
      Staphylococcus aureus and Staphylococcus epidermidis. Wistar rats with puncture
      wounded skin were used to evaluate the wound healing properties of propolis. The
      results of chemical and biological characterization demonstrated the batch-to
      batch reproducibility of the standardized extract which is an unprecedented
      result. The antimicrobial and wound healing activity of the pharmaceutical
      studied showed the best results when samples contain 3.6% propolis, suggesting
      that this is the most promising composition.

PMID- 22457607
TI  - TWIST represses estrogen receptor-alpha expression by recruiting the NuRD protein
      complex in breast cancer cells.
AB  - Loss of estrogen receptor alpha (ERalpha) expression and gain of TWIST (TWIST1)
      expression in breast tumors correlate with increased disease recurrence and
      metastasis and poor disease-free survival. However, the molecular and functional
      regulatory relationship between TWIST and ERalpha are unclear. In this study, we
      found TWIST was associated with a chromatin region in intron 7 of the human ESR1
      gene coding for ERalpha. This association of TWIST efficiently recruited the
      nucleosome remodeling and deacetylase (NuRD) repressor complex to this region,
      which subsequently decreased histone H3K9 acetylation, increased histone H3K9
      methylation and repressed ESR1 expression in breast cancer cells. In agreement
      with these molecular events, TWIST expression was inversely correlated with
      ERalpha expression in both breast cancer cell lines and human breast ductal
      carcinomas. Forced expression of TWIST in TWIST-negative and ERalpha-positive
      breast cancer cells such as T47D and MCF-7 cells reduced ERalpha expression,
      while knockdown of TWIST in TWIST-positive and ERalpha-negative breast cancer
      cells such as MDA-MB-435 and 4T1 cells increased ERalpha expression. Furthermore,
      inhibition of histone deacetylase (HDAC) activity including the one in NuRD
      complex significantly increased ERalpha expression in MDA-MB-435 and 4T1 cells.
      HDAC inhibition together with TWIST knockdown did not further increase ERalpha
      expression in 4T1 and MDA-MB-435 cells. These results demonstrate that TWIST/NuRD
      represses ERalpha expression in breast cancer cells. Therefore, TWIST may serve
      as a potential molecular target for converting ERalpha-negative breast cancers to
      ERalpha-positive breast cancers, allowing these cancers to restore their
      sensitivity to endocrine therapy with selective ERalpha antagonists such as
      tamoxifen and raloxifene.

PMID- 22457608
TI  - Impact of network structure and cellular response on spike time correlations.
AB  - Novel experimental techniques reveal the simultaneous activity of larger and
      larger numbers of neurons. As a result there is increasing interest in the
      structure of cooperative--or correlated--activity in neural populations, and in
      the possible impact of such correlations on the neural code. A fundamental
      theoretical challenge is to understand how the architecture of network
      connectivity along with the dynamical properties of single cells shape the
      magnitude and timescale of correlations. We provide a general approach to this
      problem by extending prior techniques based on linear response theory. We
      consider networks of general integrate-and-fire cells with arbitrary
      architecture, and provide explicit expressions for the approximate cross
      correlation between constituent cells. These correlations depend strongly on the
      operating point (input mean and variance) of the neurons, even when connectivity
      is fixed. Moreover, the approximations admit an expansion in powers of the
      matrices that describe the network architecture. This expansion can be readily
      interpreted in terms of paths between different cells. We apply our results to
      large excitatory-inhibitory networks, and demonstrate first how precise balance-
      or lack thereof--between the strengths and timescales of excitatory and
      inhibitory synapses is reflected in the overall correlation structure of the
      network. We then derive explicit expressions for the average correlation
      structure in randomly connected networks. These expressions help to identify the
      important factors that shape coordinated neural activity in such networks.

PMID- 22457609
TI  - Implications of behavioral architecture for the evolution of self-organized
      division of labor.
AB  - Division of labor has been studied separately from a proximate self-organization
      and an ultimate evolutionary perspective. We aim to bring together these two
      perspectives. So far this has been done by choosing a behavioral mechanism a
      priori and considering the evolution of the properties of this mechanism. Here we
      use artificial neural networks to allow for a more open architecture. We study
      whether emergent division of labor can evolve in two different network
      architectures; a simple feedforward network, and a more complex network that
      includes the possibility of self-feedback from previous experiences. We focus on
      two aspects of division of labor; worker specialization and the ratio of work
      performed for each task. Colony fitness is maximized by both reducing idleness
      and achieving a predefined optimal work ratio. Our results indicate that
      architectural constraints play an important role for the outcome of evolution.
      With the simplest network, only genetically determined specialization is
      possible. This imposes several limitations on worker specialization. Moreover, in
      order to minimize idleness, networks evolve a biased work ratio, even when an
      unbiased work ratio would be optimal. By adding self-feedback to the network we
      increase the network's flexibility and worker specialization evolves under a
      wider parameter range. Optimal work ratios are more easily achieved with the self
      feedback network, but still provide a challenge when combined with worker
      specialization.

PMID- 22457610
TI  - Feedforward inhibition and synaptic scaling--two sides of the same coin?
AB  - Feedforward inhibition and synaptic scaling are important adaptive processes that
      control the total input a neuron can receive from its afferents. While often
      studied in isolation, the two have been reported to co-occur in various brain
      regions. The functional implications of their interactions remain unclear,
      however. Based on a probabilistic modeling approach, we show here that fast
      feedforward inhibition and synaptic scaling interact synergistically during
      unsupervised learning. In technical terms, we model the input to a neural circuit
      using a normalized mixture model with Poisson noise. We demonstrate analytically
      and numerically that, in the presence of lateral inhibition introducing
      competition between different neurons, Hebbian plasticity and synaptic scaling
      approximate the optimal maximum likelihood solutions for this model. Our results
      suggest that, beyond its conventional use as a mechanism to remove undesired
      pattern variations, input normalization can make typical neural interaction and
      learning rules optimal on the stimulus subspace defined through feedforward
      inhibition. Furthermore, learning within this subspace is more efficient in
      practice, as it helps avoid locally optimal solutions. Our results suggest a
      close connection between feedforward inhibition and synaptic scaling which may
      have important functional implications for general cortical processing.

PMID- 22457611
TI  - Corresponding functional dynamics across the Hsp90 Chaperone family: insights
      from a multiscale analysis of MD simulations.
AB  - Understanding how local protein modifications, such as binding small-molecule
      ligands, can trigger and regulate large-scale motions of large protein domains is
      a major open issue in molecular biology. We address various aspects of this
      problem by analyzing and comparing atomistic simulations of Hsp90 family
      representatives for which crystal structures of the full length protein are
      available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are
      studied in complex with the natural ligands ATP, ADP and in the Apo state. Common
      key aspects of their functional dynamics are elucidated with a novel multi-scale
      comparison of their internal dynamics. Starting from the atomic resolution
      investigation of internal fluctuations and geometric strain patterns, a novel
      analysis of domain dynamics is developed. The results reveal that the ligand
      dependent structural modulations mostly consist of relative rigid-like movements
      of a limited number of quasi-rigid domains, shared by the three proteins. Two
      common primary hinges for such movements are identified. The first hinge, whose
      functional role has been demonstrated by several experimental approaches, is
      located at the boundary between the N-terminal and Middle-domains. The second
      hinge is located at the end of a three-helix bundle in the Middle-domain and
      unfolds/unpacks going from the ATP- to the ADP-state. This latter site could
      represent a promising novel druggable allosteric site common to all chaperones.

PMID- 22457612
TI  - Hemodynamic traveling waves in human visual cortex.
AB  - Functional MRI (fMRI) experiments rely on precise characterization of the blood
      oxygen level dependent (BOLD) signal. As the spatial resolution of fMRI reaches
      the sub-millimeter range, the need for quantitative modelling of spatiotemporal
      properties of this hemodynamic signal has become pressing. Here, we find that a
      detailed physiologically-based model of spatiotemporal BOLD responses predicts
      traveling waves with velocities and spatial ranges in empirically observable
      ranges. Two measurable parameters, related to physiology, characterize these
      waves: wave velocity and damping rate. To test these predictions, high-resolution
      fMRI data are acquired from subjects viewing discrete visual stimuli. Predictions
      and experiment show strong agreement, in particular confirming BOLD waves
      propagating for at least 5-10 mm across the cortical surface at speeds of 2-12 mm
      s-1. These observations enable fundamentally new approaches to fMRI analysis,
      crucial for fMRI data acquired at high spatial resolution.

PMID- 22457613
TI  - Influence of the fibroblastic reticular network on cell-cell interactions in
      lymphoid organs.
AB  - Secondary lymphoid organs (SLO), such as lymph nodes and the spleen, display a
      complex micro-architecture. In the T cell zone the micro-architecture is provided
      by a network of fibroblastic reticular cells (FRC) and their filaments. The FRC
      network is thought to enhance the interaction between immune cells and their
      cognate antigen. However, the effect of the FRC network on cell interaction
      cannot be quantified to date because of limitations in immunological methodology.
      We use computational models to study the influence of different densities of FRC
      networks on the probability that two cells meet. We developed a 3D cellular
      automaton model to simulate cell movements and interactions along the FRC network
      inside lymphatic tissue. We show that the FRC network density has only a small
      effect on the probability of a cell to come into contact with a static or motile
      target. However, damage caused by a disruption of the FRC network is greatest at
      FRC densities corresponding to densities observed in the spleen of naive mice.
      Our analysis suggests that the FRC network as a guiding structure for moving T
      cells has only a minor effect on the probability to find a corresponding
      dendritic cell. We propose alternative hypotheses by which the FRC network might
      influence the functionality of immune responses in a more significant way.

PMID- 22457615
TI  - Traffic instabilities in self-organized pedestrian crowds.
AB  - In human crowds as well as in many animal societies, local interactions among
      individuals often give rise to self-organized collective organizations that offer
      functional benefits to the group. For instance, flows of pedestrians moving in
      opposite directions spontaneously segregate into lanes of uniform walking
      directions. This phenomenon is often referred to as a smart collective pattern,
      as it increases the traffic efficiency with no need of external control. However,
      the functional benefits of this emergent organization have never been
      experimentally measured, and the underlying behavioral mechanisms are poorly
      understood. In this work, we have studied this phenomenon under controlled
      laboratory conditions. We found that the traffic segregation exhibits structural
      instabilities characterized by the alternation of organized and disorganized
      states, where the lifetime of well-organized clusters of pedestrians follow a
      stretched exponential relaxation process. Further analysis show that the inter
      pedestrian variability of comfortable walking speeds is a key variable at the
      origin of the observed traffic perturbations. We show that the collective benefit
      of the emerging pattern is maximized when all pedestrians walk at the average
      speed of the group. In practice, however, local interactions between slow- and
      fast-walking pedestrians trigger global breakdowns of organization, which reduce
      the collective and the individual payoff provided by the traffic segregation.
      This work is a step ahead toward the understanding of traffic self-organization
      in crowds, which turns out to be modulated by complex behavioral mechanisms that
      do not always maximize the group's benefits. The quantitative understanding of
      crowd behaviors opens the way for designing bottom-up management strategies bound
      to promote the emergence of efficient collective behaviors in crowds.

PMID- 22457614
TI  - Dynamic effective connectivity of inter-areal brain circuits.
AB  - Anatomic connections between brain areas affect information flow between neuronal
      circuits and the synchronization of neuronal activity. However, such structural
      connectivity does not coincide with effective connectivity (or, more precisely,
      causal connectivity), related to the elusive question "Which areas cause the
      present activity of which others?". Effective connectivity is directed and
      depends flexibly on contexts and tasks. Here we show that dynamic effective
      connectivity can emerge from transitions in the collective organization of
      coherent neural activity. Integrating simulation and semi-analytic approaches, we
      study mesoscale network motifs of interacting cortical areas, modeled as large
      random networks of spiking neurons or as simple rate units. Through a causal
      analysis of time-series of model neural activity, we show that different
      dynamical states generated by a same structural connectivity motif correspond to
      distinct effective connectivity motifs. Such effective motifs can display a
      dominant directionality, due to spontaneous symmetry breaking and effective
      entrainment between local brain rhythms, although all connections in the
      considered structural motifs are reciprocal. We show then that transitions
      between effective connectivity configurations (like, for instance, reversal in
      the direction of inter-areal interactions) can be triggered reliably by brief
      perturbation inputs, properly timed with respect to an ongoing local oscillation,
      without the need for plastic synaptic changes. Finally, we analyze how the
      information encoded in spiking patterns of a local neuronal population is
      propagated across a fixed structural connectivity motif, demonstrating that
      changes in the active effective connectivity regulate both the efficiency and the
      directionality of information transfer. Previous studies stressed the role played
      by coherent oscillations in establishing efficient communication between distant
      areas. Going beyond these early proposals, we advance here that dynamic
      interactions between brain rhythms provide as well the basis for the self
      organized control of this "communication-through-coherence", making thus possible
      a fast "on-demand" reconfiguration of global information routing modalities.

PMID- 22457616
TI  - Sleeping with the enemy: how intracellular pathogens cope with a macrophage
      lifestyle.

PMID- 22457618
TI  - Additive function of Vibrio vulnificus MARTX(Vv) and VvhA cytolysins promotes
      rapid growth and epithelial tissue necrosis during intestinal infection.
AB  - Vibrio vulnificus is a pathogen that causes both severe necrotizing wound
      infections and life-threatening food-borne infections. Food-borne infection is
      particularly lethal as the infection can progress rapidly to primary septicemia
      resulting in death from septic shock and multiorgan failure. In this study, we
      use both bioluminescence whole animal imaging and V. vulnificus bacterial
      colonization of orally infected mice to demonstrate that the secreted
      multifunctional-autoprocessing RTX toxin (MARTX(Vv)) and the cytolysin/hemolysin
      VvhA of clinical isolate CMCP6 have an important function in the gut to promote
      early in vivo growth and dissemination of this pathogen from the small intestine
      to other organs. Using histopathology, we find that both cytotoxins can cause
      villi disruption, epithelial necrosis, and inflammation in the mouse small
      intestine. A double mutant deleted of genes for both cytotoxins was essentially
      avirulent, did not cause intestinal epithelial tissue damage, and was cleared
      from infected mice by 36 hours by an effective immune response. Therefore,
      MARTX(Vv) and VvhA seem to play an additive role for pathogenesis of CMCP6
      causing intestinal tissue damage and inflammation that then promotes
      dissemination of the infecting bacteria to the bloodstream and other organs. In
      the absence of these two secreted factors, we propose that this bacterium is
      unable to cause intestinal infection in humans.

PMID- 22457617
TI  - Comparative genomics of the apicomplexan parasites Toxoplasma gondii and Neospora
      caninum: Coccidia differing in host range and transmission strategy.
AB  - Toxoplasma gondii is a zoonotic protozoan parasite which infects nearly one third
      of the human population and is found in an extraordinary range of vertebrate
      hosts. Its epidemiology depends heavily on horizontal transmission, especially
      between rodents and its definitive host, the cat. Neospora caninum is a recently
      discovered close relative of Toxoplasma, whose definitive host is the dog. Both
      species are tissue-dwelling Coccidia and members of the phylum Apicomplexa; they
      share many common features, but Neospora neither infects humans nor shares the
      same wide host range as Toxoplasma, rather it shows a striking preference for
      highly efficient vertical transmission in cattle. These species therefore provide
      a remarkable opportunity to investigate mechanisms of host restriction,
      transmission strategies, virulence and zoonotic potential. We sequenced the
      genome of N. caninum and transcriptomes of the invasive stage of both species,
      undertaking an extensive comparative genomics and transcriptomics analysis. We
      estimate that these organisms diverged from their common ancestor around 28
      million years ago and find that both genomes and gene expression are remarkably
      conserved. However, in N. caninum we identified an unexpected expansion of
      surface antigen gene families and the divergence of secreted virulence factors,
      including rhoptry kinases. Specifically we show that the rhoptry kinase ROP18 is
      pseudogenised in N. caninum and that, as a possible consequence, Neospora is
      unable to phosphorylate host immunity-related GTPases, as Toxoplasma does. This
      defense strategy is thought to be key to virulence in Toxoplasma. We conclude
      that the ecological niches occupied by these species are influenced by a
      relatively small number of gene products which operate at the host-parasite
      interface and that the dominance of vertical transmission in N. caninum may be
      associated with the evolution of reduced virulence in this species.

PMID- 22457619
TI  - Dengue virus infection perturbs lipid homeostasis in infected mosquito cells.
AB  - Dengue virus causes ~50-100 million infections per year and thus is considered
      one of the most aggressive arthropod-borne human pathogen worldwide. During its
      replication, dengue virus induces dramatic alterations in the intracellular
      membranes of infected cells. This phenomenon is observed both in human and vector
      derived cells. Using high-resolution mass spectrometry of mosquito cells, we show
      that this membrane remodeling is directly linked to a unique lipid repertoire
      induced by dengue virus infection. Specifically, 15% of the metabolites detected
      were significantly different between DENV infected and uninfected cells while 85%
      of the metabolites detected were significantly different in isolated replication
      complex membranes. Furthermore, we demonstrate that intracellular lipid
      redistribution induced by the inhibition of fatty acid synthase, the rate
      limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is
      inhibitory to dengue virus replication. Lipids that have the capacity to
      destabilize and change the curvature of membranes as well as lipids that change
      the permeability of membranes are enriched in dengue virus infected cells.
      Several sphingolipids and other bioactive signaling molecules that are involved
      in controlling membrane fusion, fission, and trafficking as well as molecules
      that influence cytoskeletal reorganization are also up regulated during dengue
      infection. These observations shed light on the emerging role of lipids in
      shaping the membrane and protein environments during viral infections and suggest
      membrane-organizing principles that may influence virus-induced intracellular
      membrane architecture.

PMID- 22457620
TI  - Mannose binding lectin is required for alphavirus-induced arthritis/myositis.
AB  - Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV)
      are emerging pathogens capable of causing large-scale epidemics of virus-induced
      arthritis and myositis. The pathology of RRV-induced disease in both humans and
      mice is associated with induction of the host inflammatory response within the
      muscle and joints, and prior studies have demonstrated that the host complement
      system contributes to development of disease. In this study, we have used a mouse
      model of RRV-induced disease to identify and characterize which complement
      activation pathways mediate disease progression after infection, and we have
      identified the mannose binding lectin (MBL) pathway, but not the classical or
      alternative complement activation pathways, as essential for development of RRV
      induced disease. MBL deposition was enhanced in RRV infected muscle tissue from
      wild type mice and RRV infected MBL deficient mice exhibited reduced disease,
      tissue damage, and complement deposition compared to wild-type mice. In contrast,
      mice deficient for key components of the classical or alternative complement
      activation pathways still developed severe RRV-induced disease. Further
      characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice,
      viral replication and inflammatory cell recruitment were equivalent to wild type
      animals, suggesting that RRV-mediated induction of complement dependent immune
      pathology is largely MBL dependent. Consistent with these findings, human
      patients diagnosed with RRV disease had elevated serum MBL levels compared to
      healthy controls, and MBL levels in the serum and synovial fluid correlated with
      severity of disease. These findings demonstrate a role for MBL in promoting RRV
      induced disease in both mice and humans and suggest that the MBL pathway of
      complement activation may be an effective target for therapeutic intervention for
      humans suffering from RRV-induced arthritis and myositis.

PMID- 22457621
TI  - A single nucleotide polymorphism in tetherin promotes retrovirus restriction in
      vivo.
AB  - Tetherin is a membrane protein of unusual topology expressed from rodents to
      humans that accumulates enveloped virus particles on the surface of infected
      cells. However, whether this 'tethering' activity promotes or restricts
      retroviral spread during acute retrovirus infection in vivo is controversial. We
      report here the identification of a single nucleotide polymorphism in the
      Tetherin gene of NZW/LacJ (NZW) mice that mutated the canonical ATG start site to
      GTG. Translation of NZW Tetherin from downstream ATGs deleted a conserved dual
      tyrosine endosomal sorting motif, resulting in higher cell surface expression and
      more potent inhibition of Friend retrovirus release compared to C57BL/6 (B6)
      Tetherin in vitro. Analysis of (B6*NZW)F(1) hybrid mice revealed that increased
      Tetherin cell surface expression in NZW mice is a recessive trait in vivo. Using
      a classical genetic backcrossing approach, NZW Tetherin expression strongly
      correlated with decreased Friend retrovirus replication and pathogenesis.
      However, the protective effect of NZW Tetherin was not observed in the context of
      B6 Apobec3/Rfv3 resistance. These findings identify the first functional Tetherin
      polymorphism within a mammalian host, demonstrate that Tetherin cell surface
      expression is a key parameter for retroviral restriction, and suggest the
      existence of a restriction factor hierarchy to counteract pathogenic retrovirus
      infections in vivo.

PMID- 22457622
TI  - The core protein of classical Swine Fever virus is dispensable for virus
      propagation in vitro.
AB  - Core protein of Flaviviridae is regarded as essential factor for nucleocapsid
      formation. Yet, core protein is not encoded by all isolates (GBV- A and GBV- C).
      Pestiviruses are a genus within the family Flaviviridae that affect cloven-hoofed
      animals, causing economically important diseases like classical swine fever (CSF)
      and bovine viral diarrhea (BVD). Recent findings describe the ability of NS3 of
      classical swine fever virus (CSFV) to compensate for disabling size increase of
      core protein (Riedel et al., 2010). NS3 is a nonstructural protein possessing
      protease, helicase and NTPase activity and a key player in virus replication. A
      role of NS3 in particle morphogenesis has also been described for other members
      of the Flaviviridae (Patkar et al., 2008; Ma et al., 2008). These findings raise
      questions about the necessity and function of core protein and the role of NS3 in
      particle assembly. A reverse genetic system for CSFV was employed to generate
      poorly growing CSFVs by modification of the core gene. After passaging, rescued
      viruses had acquired single amino acid substitutions (SAAS) within NS3 helicase
      subdomain 3. Upon introduction of these SAAS in a nonviable CSFV with deletion of
      almost the entire core gene (Vp447(Deltac)), virus could be rescued. Further
      characterization of this virus with regard to its physical properties, morphology
      and behavior in cell culture did not reveal major differences between wildtype
      (Vp447) and Vp447(Deltac). Upon infection of the natural host, Vp447(Deltac) was
      attenuated. Hence we conclude that core protein is not essential for particle
      assembly of a core-encoding member of the Flaviviridae, but important for its
      virulence. This raises questions about capsid structure and necessity, the role
      of NS3 in particle assembly and the function of core protein in general.

PMID- 22457623
TI  - Direct recognition of Fusobacterium nucleatum by the NK cell natural cytotoxicity
      receptor NKp46 aggravates periodontal disease.
AB  - Periodontitis is a common human chronic inflammatory disease that results in the
      destruction of the tooth attachment apparatus and tooth loss. Although infections
      with periopathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis)
      and Fusobacterium nucleatum (F. nucleatum) are essential for inducing
      periodontitis, the nature and magnitude of the disease is determined by the
      host's immune response. Here, we investigate the role played by the NK killer
      receptor NKp46 (NCR1 in mice), in the pathogenesis of periodontitis. Using an
      oral infection periodontitis model we demonstrate that following F. nucleatum
      infection no alveolar bone loss is observed in mice deficient for NCR1
      expression, whereas around 20% bone loss is observed in wild type mice and in
      mice infected with P. gingivalis. By using subcutaneous chambers inoculated with
      F. nucleatum we demonstrate that immune cells, including NK cells, rapidly
      accumulate in the chambers and that this leads to a fast and transient, NCR1
      dependant TNF-alpha secretion. We further show that both the mouse NCR1 and the
      human NKp46 bind directly to F. nucleatum and we demonstrate that this binding is
      sensitive to heat, to proteinase K and to pronase treatments. Finally, we show in
      vitro that the interaction of NK cells with F. nucleatum leads to an NCR1
      dependent secretion of TNF-alpha. Thus, the present study provides the first
      evidence that NCR1 and NKp46 directly recognize a periodontal pathogen and that
      this interaction influences the outcome of F. nucleatum-mediated periodontitis.

PMID- 22457624
TI  - Peptidoglycan-modifying enzyme Pgp1 is required for helical cell shape and
      pathogenicity traits in Campylobacter jejuni.
AB  - The impact of bacterial morphology on virulence and transmission attributes of
      pathogens is poorly understood. The prevalent enteric pathogen Campylobacter
      jejuni displays a helical shape postulated as important for colonization and host
      interactions. However, this had not previously been demonstrated experimentally.
      C. jejuni is thus a good organism for exploring the role of factors modulating
      helical morphology on pathogenesis. We identified an uncharacterized gene,
      designated pgp1 (peptidoglycan peptidase 1), in a calcofluor white-based screen
      to explore cell envelope properties important for C. jejuni virulence and stress
      survival. Bioinformatics showed that Pgp1 is conserved primarily in curved and
      helical bacteria. Deletion of pgp1 resulted in a striking, rod-shaped morphology,
      making pgp1 the first C. jejuni gene shown to be involved in maintenance of C.
      jejuni cell shape. Pgp1 contributes to key pathogenic and cell envelope
      phenotypes. In comparison to wild type, the rod-shaped pgp1 mutant was deficient
      in chick colonization by over three orders of magnitude and elicited enhanced
      secretion of the chemokine IL-8 in epithelial cell infections. Both the pgp1
      mutant and a pgp1 overexpressing strain - which similarly produced straight or
      kinked cells - exhibited biofilm and motility defects. Detailed peptidoglycan
      analyses via HPLC and mass spectrometry, as well as Pgp1 enzyme assays, confirmed
      Pgp1 as a novel peptidoglycan DL-carboxypeptidase cleaving monomeric tripeptides
      to dipeptides. Peptidoglycan from the pgp1 mutant activated the host cell
      receptor Nod1 to a greater extent than did that of wild type. This work provides
      the first link between a C. jejuni gene and morphology, peptidoglycan
      biosynthesis, and key host- and transmission-related characteristics.

PMID- 22457625
TI  - Multiple peptidoglycan modification networks modulate Helicobacter pylori's cell
      shape, motility, and colonization potential.
AB  - Helical cell shape of the gastric pathogen Helicobacter pylori has been suggested
      to promote virulence through viscosity-dependent enhancement of swimming
      velocity. However, H. pylori csd1 mutants, which are curved but lack helical
      twist, show normal velocity in viscous polymer solutions and the reason for their
      deficiency in stomach colonization has remained unclear. Characterization of new
      rod shaped mutants identified Csd4, a DL-carboxypeptidase of peptidoglycan (PG)
      tripeptide monomers and Csd5, a putative scaffolding protein. Morphological and
      biochemical studies indicated Csd4 tripeptide cleavage and Csd1 crosslinking
      relaxation modify the PG sacculus through independent networks that coordinately
      generate helical shape. csd4 mutants show attenuation of stomach colonization,
      but no change in proinflammatory cytokine induction, despite four-fold higher
      levels of Nod1-agonist tripeptides in the PG sacculus. Motility analysis of
      similarly shaped mutants bearing distinct alterations in PG modifications
      revealed deficits associated with shape, but only in gel-like media and not
      viscous solutions. As gastric mucus displays viscoelastic gel-like properties,
      our results suggest enhanced penetration of the mucus barrier underlies the
      fitness advantage conferred by H. pylori's characteristic shape.

PMID- 22457626
TI  - Chemoenzymatic site-specific labeling of influenza glycoproteins as a tool to
      observe virus budding in real time.
AB  - The influenza virus uses the hemagglutinin (HA) and neuraminidase (NA)
      glycoproteins to interact with and infect host cells. While biochemical and
      microscopic methods allow examination of the early steps in flu infection, the
      genesis of progeny virions has been more difficult to follow, mainly because of
      difficulties inherent in fluorescent labeling of flu proteins in a manner
      compatible with live cell imaging. We here apply sortagging as a chemoenzymatic
      approach to label genetically modified but infectious flu and track the flu
      glycoproteins during the course of infection. This method cleanly distinguishes
      influenza glycoproteins from host glycoproteins and so can be used to assess the
      behavior of HA or NA biochemically and to observe the flu glycoproteins directly
      by live cell imaging.

PMID- 22457627
TI  - Inactivation of staphylococcal phenol soluble modulins by serum lipoprotein
      particles.
AB  - Staphylococcus aureus virulence has been associated with the production of phenol
      soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils.
      However, the functional characterizations were generally performed in the absence
      of human serum. Here, we demonstrate that human serum can inhibit all the
      previously-described activities of PSM. We observed that serum can fully block
      both the cell lysis and FPR2 activation of neutrophils. We show a direct
      interaction between PSM and serum lipoproteins in human serum and whole blood.
      Subsequent analysis using purified high, low, and very low density lipoproteins
      (HDL, LDL, and VLDL) revealed that they indeed neutralize PSM. The lipoprotein
      HDL showed highest binding and antagonizing capacity for PSM. Furthermore, we
      show potential intracellular production of PSM by S. aureus upon phagocytosis by
      neutrophils, which opens a new area for exploration of the intracellular lytic
      capacity of PSM. Collectively, our data show that in a serum environment the
      function of PSM as important extracellular toxins should be reconsidered.

PMID- 22457628
TI  - Induced release of a plant-defense volatile 'deceptively' attracts insect vectors
      to plants infected with a bacterial pathogen.
AB  - Transmission of plant pathogens by insect vectors is a complex biological process
      involving interactions between the plant, insect, and pathogen. Pathogen-induced
      plant responses can include changes in volatile and nonvolatile secondary
      metabolites as well as major plant nutrients. Experiments were conducted to
      understand how a plant pathogenic bacterium, Candidatus Liberibacter asiaticus
      (Las), affects host preference behavior of its psyllid (Diaphorina citri
      Kuwayama) vector. D. citri were attracted to volatiles from pathogen-infected
      plants more than to those from non-infected counterparts. Las-infected plants
      were more attractive to D. citri adults than non-infected plants initially;
      however after feeding, psyllids subsequently dispersed to non-infected rather
      than infected plants as their preferred settling point. Experiments with Las
      infected and non-infected plants under complete darkness yielded similar results
      to those recorded under light. The behavior of psyllids in response to infected
      versus non-infected plants was not influenced by whether or not they were
      carriers of the pathogen. Quantification of volatile release from non-infected
      and infected plants supported the hypothesis that odorants mediate psyllid
      preference. Significantly more methyl salicylate, yet less methyl anthranilate
      and D-limonene, was released by infected than non-infected plants. Methyl
      salicylate was attractive to psyllids, while methyl anthranilate did not affect
      their behavior. Feeding on citrus by D. citri adults also induced release of
      methyl salicylate, suggesting that it may be a cue revealing location of
      conspecifics on host plants. Infected plants were characterized by lower levels
      of nitrogen, phosphorus, sulfur, zinc, and iron, as well as, higher levels of
      potassium and boron than non-infected plants. Collectively, our results suggest
      that host selection behavior of D. citri may be modified by bacterial infection
      of plants, which alters release of specific headspace volatiles and plant
      nutritional contents. Furthermore, we show in a laboratory setting that this
      apparent pathogen-mediated manipulation of vector behavior may facilitate
      pathogen spread.

PMID- 22457629
TI  - Thriving under stress: selective translation of HIV-1 structural protein mRNA
      during Vpr-mediated impairment of eIF4E translation activity.
AB  - Translation is a regulated process and is pivotal to proper cell growth and
      homeostasis. All retroviruses rely on the host translational machinery for viral
      protein synthesis and thus may be susceptible to its perturbation in response to
      stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell
      cycle in the G2/M phase, potentially disrupting the regulation of host cell
      translation. In this study, we present evidence that HIV-1 infection
      downregulates translation in lymphocytes, attributable to the cell cycle arrest
      induced by the HIV-1 accessory protein Vpr. The molecular basis of the
      translation suppression is reduced accumulation of the active form of the
      translation initiation factor 4E (eIF4E). However, synthesis of viral structural
      proteins is sustained despite the general suppression of protein production. HIV
      1 mRNA translation is sustained due to the distinct composition of the HIV-1
      ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the
      HIV-1 unspliced and singly spliced transcripts are predominantly associated with
      nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral
      and cellular mRNAs that are associated with eIF4E. The active translation of the
      nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal
      RNA profile analyses. Thus, our findings have uncovered that the maintenance of
      CBC association is a novel mechanism used by HIV-1 to bypass downregulation of
      eIF4E activity and sustain viral protein synthesis. We speculate that a subset of
      CBP80-bound cellular mRNAs contribute to recovery from significant cellular
      stress, including human retrovirus infection.

PMID- 22457631
TI  - Contrasted patterns of molecular evolution in dominant and recessive self
      incompatibility haplotypes in Arabidopsis.
AB  - Self-incompatibility has been considered by geneticists a model system for
      reproductive biology and balancing selection, but our understanding of the
      genetic basis and evolution of this molecular lock-and-key system has remained
      limited by the extreme level of sequence divergence among haplotypes, resulting
      in a lack of appropriate genomic sequences. In this study, we report and analyze
      the full sequence of eleven distinct haplotypes of the self-incompatibility locus
      (S-locus) in two closely related Arabidopsis species, obtained from individual
      BAC libraries. We use this extensive dataset to highlight sharply contrasted
      patterns of molecular evolution of each of the two genes controlling self
      incompatibility themselves, as well as of the genomic region surrounding them. We
      find strong collinearity of the flanking regions among haplotypes on each side of
      the S-locus together with high levels of sequence similarity. In contrast, the S
      locus region itself shows spectacularly deep gene genealogies, high variability
      in size and gene organization, as well as complete absence of sequence similarity
      in intergenic sequences and striking accumulation of transposable elements. Of
      particular interest, we demonstrate that dominant and recessive S-haplotypes
      experience sharply contrasted patterns of molecular evolution. Indeed, dominant
      haplotypes exhibit larger size and a much higher density of transposable
      elements, being matched only by that in the centromere. Overall, these properties
      highlight that the S-locus presents many striking similarities with other regions
      involved in the determination of mating-types, such as sex chromosomes in animals
      or in plants, or the mating-type locus in fungi and green algae.

PMID- 22457632
TI  - EMF1 and PRC2 cooperate to repress key regulators of Arabidopsis development.
AB  - EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene crucial to Arabidopsis
      vegetative development. Loss of function mutants in the EMF1 gene mimic the
      phenotype caused by mutations in Polycomb Group protein (PcG) genes, which encode
      epigenetic repressors that regulate many aspects of eukaryotic development. In
      Arabidopsis, Polycomb Repressor Complex 2 (PRC2), made of PcG proteins, catalyzes
      trimethylation of lysine 27 on histone H3 (H3K27me3) and PRC1-like proteins
      catalyze H2AK119 ubiquitination. Despite functional similarity to PcG proteins,
      EMF1 lacks sequence homology with known PcG proteins; thus, its role in the PcG
      mechanism is unclear. To study the EMF1 functions and its mechanism of action, we
      performed genome-wide mapping of EMF1 binding and H3K27me3 modification sites in
      Arabidopsis seedlings. The EMF1 binding pattern is similar to that of H3K27me3
      modification on the chromosomal and genic level. ChIPOTLe peak finding and
      clustering analyses both show that the highly trimethylated genes also have high
      enrichment levels of EMF1 binding, termed EMF1_K27 genes. EMF1 interacts with
      regulatory genes, which are silenced to allow vegetative growth, and with genes
      specifying cell fates during growth and differentiation. H3K27me3 marks not only
      these genes but also some genes that are involved in endosperm development and
      maternal effects. Transcriptome analysis, coupled with the H3K27me3 pattern, of
      EMF1_K27 genes in emf1 and PRC2 mutants showed that EMF1 represses gene
      activities via diverse mechanisms and plays a novel role in the PcG mechanism.

PMID- 22457634
TI  - The Min system and nucleoid occlusion are not required for identifying the
      division site in Bacillus subtilis but ensure its efficient utilization.
AB  - Precise temporal and spatial control of cell division is essential for progeny
      survival. The current general view is that precise positioning of the division
      site at midcell in rod-shaped bacteria is a result of the combined action of the
      Min system and nucleoid (chromosome) occlusion. Both systems prevent assembly of
      the cytokinetic Z ring at inappropriate places in the cell, restricting Z rings
      to the correct site at midcell. Here we show that in the bacterium Bacillus
      subtilis Z rings are positioned precisely at midcell in the complete absence of
      both these systems, revealing the existence of a mechanism independent of Min and
      nucleoid occlusion that identifies midcell in this organism. We further show that
      Z ring assembly at midcell is delayed in the absence of Min and Noc proteins,
      while at the same time FtsZ accumulates at other potential division sites. This
      suggests that a major role for Min and Noc is to ensure efficient utilization of
      the midcell division site by preventing Z ring assembly at potential division
      sites, including the cell poles. Our data lead us to propose a model in which
      spatial regulation of division in B. subtilis involves identification of the
      division site at midcell that requires Min and nucleoid occlusion to ensure
      efficient Z ring assembly there and only there, at the right time in the cell
      cycle.

PMID- 22457633
TI  - APOBEC3G-induced hypermutation of human immunodeficiency virus type-1 is
      typically a discrete "all or nothing" phenomenon.
AB  - The rapid evolution of Human Immunodeficiency Virus (HIV-1) allows studies of
      ongoing host-pathogen interactions. One key selective host factor is APOBEC3G
      (hA3G) that can cause extensive and inactivating Guanosine-to-Adenosine (G-to-A)
      mutation on HIV plus-strand DNA (termed hypermutation). HIV can inhibit this
      innate anti-viral defense through binding of the viral protein Vif to hA3G, but
      binding efficiency varies and hypermutation frequencies fluctuate in patients. A
      pivotal question is whether hA3G-induced G-to-A mutation is always lethal to the
      virus or if it may occur at sub-lethal frequencies that could increase viral
      diversification. We show in vitro that limiting-levels of hA3G-activity (i.e.
      when only a single hA3G-unit is likely to act on HIV) produce hypermutation
      frequencies similar to those in patients and demonstrate in silico that
      potentially non-lethal G-to-A mutation rates are ~10-fold lower than the lowest
      observed hypermutation levels in vitro and in vivo. Our results suggest that even
      a single incorporated hA3G-unit is likely to cause extensive and inactivating
      levels of HIV hypermutation and that hypermutation therefore is typically a
      discrete "all or nothing" phenomenon. Thus, therapeutic measures that inhibit the
      interaction between Vif and hA3G will likely not increase virus diversification
      but expand the fraction of hypermutated proviruses within the infected host.

PMID- 22457635
TI  - Physiological notch signaling maintains bone homeostasis via RBPjk and Hey
      upstream of NFATc1.
AB  - Notch signaling between neighboring cells controls many cell fate decisions in
      metazoans both during embryogenesis and in postnatal life. Previously, we
      uncovered a critical role for physiological Notch signaling in suppressing
      osteoblast differentiation in vivo. However, the contribution of individual Notch
      receptors and the downstream signaling mechanism have not been elucidated. Here
      we report that removal of Notch2, but not Notch1, from the embryonic limb
      mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion
      of the transcription factor RBPjk, a mediator of all canonical Notch signaling,
      in the mesenchymal progenitors but not the more mature osteoblast-lineage cells,
      caused a dramatic high-bone-mass phenotype characterized by increased osteoblast
      numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age
      dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes
      of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to
      and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1
      expression in bone. Finally, pharmacological inhibition of NFAT alleviated the
      high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling
      functions in part through Hey1-mediated inhibition of NFATc1 to suppress
      osteoblastogenesis, contributing to bone homeostasis in vivo.

PMID- 22457636
TI  - Evidence for positive selection on a number of MicroRNA regulatory interactions
      during recent human evolution.
AB  - MicroRNA (miRNA)-mediated gene regulation is of critical functional importance in
      animals and is thought to be largely constrained during evolution. However,
      little is known regarding evolutionary changes of the miRNA network and their
      role in human evolution. Here we show that a number of miRNA binding sites
      display high levels of population differentiation in humans and thus are likely
      targets of local adaptation. In a subset we demonstrate that allelic differences
      modulate miRNA regulation in mammalian cells, including an interaction between
      miR-155 and TYRP1, an important melanosomal enzyme associated with human
      pigmentary differences. We identify alternate alleles of TYRP1 that induce or
      disrupt miR-155 regulation and demonstrate that these alleles are selected with
      different modes among human populations, causing a strong negative correlation
      between the frequency of miR-155 regulation of TYRP1 in human populations and
      their latitude of residence. We propose that local adaptation of microRNA
      regulation acts as a rheostat to optimize TYRP1 expression in response to
      differential UV radiation. Our findings illustrate the evolutionary plasticity of
      the microRNA regulatory network in recent human evolution.

PMID- 22457637
TI  - lin-28 controls the succession of cell fate choices via two distinct activities.
AB  - lin-28 is a conserved regulator of cell fate succession in animals. In
      Caenorhabditis elegans, it is a component of the heterochronic gene pathway that
      governs larval developmental timing, while its vertebrate homologs promote
      pluripotency and control differentiation in diverse tissues. The RNA binding
      protein encoded by lin-28 can directly inhibit let-7 microRNA processing by a
      novel mechanism that is conserved from worms to humans. We found that C. elegans
      LIN-28 protein can interact with four distinct let-7 family pre-microRNAs, but in
      vivo inhibits the premature accumulation of only let-7. Surprisingly, however,
      lin-28 does not require let-7 or its relatives for its characteristic promotion
      of second larval stage cell fates. In other words, we find that the premature
      accumulation of mature let-7 does not account for lin-28's precocious phenotype.
      To explain let-7's role in lin-28 activity, we provide evidence that lin-28 acts
      in two steps: first, the let-7-independent positive regulation of hbl-1 through
      its 3'UTR to control L2 stage-specific cell fates; and second, a let-7-dependent
      step that controls subsequent fates via repression of lin-41. Our evidence also
      indicates that let-7 functions one stage earlier in C. elegans development than
      previously thought. Importantly, lin-28's two-step mechanism resembles that of
      the heterochronic gene lin-14, and the overlap of their activities suggests a
      clockwork mechanism for developmental timing. Furthermore, this model explains
      the previous observation that mammalian Lin28 has two genetically separable
      activities. Thus, lin-28's two-step mechanism may be an essential feature of its
      evolutionarily conserved role in cell fate succession.

PMID- 22457638
TI  - Age-dependent brain gene expression and copy number anomalies in autism suggest
      distinct pathological processes at young versus mature ages.
AB  - Autism is a highly heritable neurodevelopmental disorder, yet the genetic
      underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a
      well-replicated observation in the autism literature; but association, linkage,
      and expression studies have not identified genetic factors that explain this
      trajectory. Few studies have had sufficient statistical power to investigate
      whole-genome gene expression and genotypic variation in the autistic brain,
      especially in regions that display the greatest growth abnormality. Previous
      functional genomic studies have identified possible alterations in transcript
      levels of genes related to neurodevelopment and immune function. Thus, there is a
      need for genetic studies involving key brain regions to replicate these findings
      and solidify the role of particular functional pathways in autism pathogenesis.
      We therefore sought to identify abnormal brain gene expression patterns via whole
      genome analysis of mRNA levels and copy number variations (CNVs) in autistic and
      control postmortem brain samples. We focused on prefrontal cortex tissue where
      excess neuron numbers and cortical overgrowth are pronounced in the majority of
      autism cases. We found evidence for dysregulation in pathways governing cell
      number, cortical patterning, and differentiation in young autistic prefrontal
      cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of
      signaling and repair pathways. Genes regulating cell cycle also exhibited autism
      specific CNVs in DNA derived from prefrontal cortex, and these genes were
      significantly associated with autism in genome-wide association study datasets.
      Our results suggest that CNVs and age-dependent gene expression changes in autism
      may reflect distinct pathological processes in the developing versus the mature
      autistic prefrontal cortex. Our results raise the hypothesis that genetic
      dysregulation in the developing brain leads to abnormal regional patterning,
      excess prefrontal neurons, cortical overgrowth, and neural dysfunction in autism.

PMID- 22457639
TI  - Cis-by-Trans regulatory divergence causes the asymmetric lethal effects of an
      ancestral hybrid incompatibility gene.
AB  - The Dobzhansky and Muller (D-M) model explains the evolution of hybrid
      incompatibility (HI) through the interaction between lineage-specific derived
      alleles at two or more loci. In agreement with the expectation that HI results
      from functional divergence, many protein-coding genes that contribute to
      incompatibilities between species show signatures of adaptive evolution,
      including Lhr, which encodes a heterochromatin protein whose amino acid sequence
      has diverged extensively between Drosophila melanogaster and D. simulans by
      natural selection. The lethality of D. melanogaster/D. simulans F1 hybrid sons is
      rescued by removing D. simulans Lhr, but not D. melanogaster Lhr, suggesting that
      the lethal effect results from adaptive evolution in the D. simulans lineage. It
      has been proposed that adaptive protein divergence in Lhr reflects antagonistic
      coevolution with species-specific heterochromatin sequences and that defects in
      LHR protein localization cause hybrid lethality. Here we present surprising
      results that are inconsistent with this coding-sequence-based model. Using Lhr
      transgenes expressed under native conditions, we find no evidence that LHR
      localization differs between D. melanogaster and D. simulans, nor do we find
      evidence that it mislocalizes in their interspecific hybrids. Rather, we
      demonstrate that Lhr orthologs are differentially expressed in the hybrid
      background, with the levels of D. simulans Lhr double that of D. melanogaster
      Lhr. We further show that this asymmetric expression is caused by cis-by-trans
      regulatory divergence of Lhr. Therefore, the non-equivalent hybrid lethal effects
      of Lhr orthologs can be explained by asymmetric expression of a molecular
      function that is shared by both orthologs and thus was presumably inherited from
      the ancestral allele of Lhr. We present a model whereby hybrid lethality occurs
      by the interaction between evolutionarily ancestral and derived alleles.

PMID- 22457640
TI  - Broad-specificity mRNA-rRNA complementarity in efficient protein translation.
AB  - Studies of synthetic, well-defined biomolecular systems can elucidate inherent
      capabilities that may be difficult to uncover in a native biological context.
      Here, we used a minimal, reconstituted translation system from Escherichia coli
      to identify efficient ribosome binding sites (RBSs) in an unbiased, high
      throughput manner. We applied ribosome display, a powerful in vitro selection
      method, to enrich only those mRNA sequences which could direct rapid protein
      translation. In addition to canonical Shine-Dalgarno (SD) motifs, we unexpectedly
      recovered highly efficient cytosine-rich (C-rich) sequences that exhibit
      unmistakable complementarity to the 16S rRNA of the small subunit of the
      ribosome, indicating that broad-specificity base-pairing may be an inherent,
      general mechanism for efficient translation. Furthermore, given the conservation
      of ribosomal structure and function across species, the broader relevance of C
      rich RBS sequences identified through our in vitro evolution approach is
      supported by multiple, diverse examples in nature, including C-rich RBSs in
      several bacteriophage and plants, a poly-C consensus before the start codon in a
      lower eukaryote, and Kozak-like sequences in vertebrates.

PMID- 22457641
TI  - Widespread site-dependent buffering of human regulatory polymorphism.
AB  - The average individual is expected to harbor thousands of variants within non
      coding genomic regions involved in gene regulation. However, it is currently not
      possible to interpret reliably the functional consequences of genetic variation
      within any given transcription factor recognition sequence. To address this, we
      comprehensively analyzed heritable genome-wide binding patterns of a major
      sequence-specific regulator (CTCF) in relation to genetic variability in binding
      site sequences across a multi-generational pedigree. We localized and quantified
      CTCF occupancy by ChIP-seq in 12 related and unrelated individuals spanning three
      generations, followed by comprehensive targeted resequencing of the entire CTCF
      binding landscape across all individuals. We identified hundreds of variants with
      reproducible quantitative effects on CTCF occupancy (both positive and negative).
      While these effects paralleled protein-DNA recognition energetics when averaged,
      they were extensively buffered by striking local context dependencies. In the
      significant majority of cases buffering was complete, resulting in silent
      variants spanning every position within the DNA recognition interface
      irrespective of level of binding energy or evolutionary constraint. The
      prevalence of complex partial or complete buffering effects severely constrained
      the ability to predict reliably the impact of variation within any given binding
      site instance. Surprisingly, 40% of variants that increased CTCF occupancy
      occurred at positions of human-chimp divergence, challenging the expectation that
      the vast majority of functional regulatory variants should be deleterious. Our
      results suggest that, even in the presence of "perfect" genetic information
      afforded by resequencing and parallel studies in multiple related individuals,
      genomic site-specific prediction of the consequences of individual variation in
      regulatory DNA will require systematic coupling with empirical functional genomic
      measurements.

PMID- 22457642
TI  - A fundamental regulatory mechanism operating through OmpR and DNA topology
      controls expression of Salmonella pathogenicity islands SPI-1 and SPI-2.
AB  - DNA topology has fundamental control over the ability of transcription factors to
      access their target DNA sites at gene promoters. However, the influence of DNA
      topology on protein-DNA and protein-protein interactions is poorly understood.
      For example, relaxation of DNA supercoiling strongly induces the well-studied
      pathogenicity gene ssrA (also called spiR) in Salmonella enterica, but neither
      the mechanism nor the proteins involved are known. We have found that relaxation
      of DNA supercoiling induces expression of the Salmonella pathogenicity island
      (SPI)-2 regulator ssrA as well as the SPI-1 regulator hilC through a mechanism
      that requires the two-component regulator OmpR-EnvZ. Additionally, the ompR
      promoter is autoregulated in the same fashion. Conversely, the SPI-1 regulator
      hilD is induced by DNA relaxation but is repressed by OmpR. Relaxation of DNA
      supercoiling caused an increase in OmpR binding to DNA and a concomitant decrease
      in binding by the nucleoid-associated protein FIS. The reciprocal occupancy of
      DNA by OmpR and FIS was not due to antagonism between these transcription
      factors, but was instead a more intrinsic response to altered DNA topology.
      Surprisingly, DNA relaxation had no detectable effect on the binding of the
      global repressor H-NS. These results reveal the underlying molecular mechanism
      that primes SPI genes for rapid induction at the onset of host invasion.
      Additionally, our results reveal novel features of the archetypal two-component
      regulator OmpR. OmpR binding to relaxed DNA appears to generate a locally
      supercoiled state, which may assist promoter activation by relocating
      supercoiling stress-induced destabilization of DNA strands. Much has been made of
      the mechanisms that have evolved to regulate horizontally-acquired genes such as
      SPIs, but parallels among the ssrA, hilC, and ompR promoters illustrate that a
      fundamental form of regulation based on DNA topology coordinates the expression
      of these genes regardless of their origins.

PMID- 22457643
TI  - Progress in the diagnosis and treatment of inflammatory bowel disease.

PMID- 22457644
TI  - The endocannabinoid system: an overview.
AB  - Upon the identification of anandamide (AEA) in the porcine brain, numerous
      studies contributed to the current state of knowledge regarding all elements that
      form the "endocannabinoid system (ECS)."How this complex system of receptors,
      ligands, and enzymes is integrated in helping to regulate fundamental processes
      at level of central nervous and peripheral systems and how its regulation and
      dysregulation might counteract disturbances of such functions, is nowadays still
      under investigation. However, the most recent advances on the physiological
      distribution and functional role of ECS allowed the progress of various research
      tools aimed at the therapeutic exploitation of endocannabinoid (eCB) signaling,
      as well as the development of novel drugs with pharmacological advantages. Here,
      we shall briefly overview the metabolic and signal transduction pathways of the
      main eCBs representatives, AEA, and 2-arachidonoylglycerol (2-AG), and we will
      discuss the therapeutic potential of new ECS-oriented drugs.

PMID- 22457645
TI  - Neuroimaging of child abuse: a critical review.
AB  - Childhood maltreatment is a stressor that can lead to the development of behavior
      problems and affect brain structure and function. This review summarizes the
      current evidence for the effects of childhood maltreatment on behavior, cognition
      and the brain in adults and children. Neuropsychological studies suggest an
      association between child abuse and deficits in IQ, memory, working memory,
      attention, response inhibition and emotion discrimination. Structural
      neuroimaging studies provide evidence for deficits in brain volume, gray and
      white matter of several regions, most prominently the dorsolateral and
      ventromedial prefrontal cortex but also hippocampus, amygdala, and corpus
      callosum (CC). Diffusion tensor imaging (DTI) studies show evidence for deficits
      in structural interregional connectivity between these areas, suggesting neural
      network abnormalities. Functional imaging studies support this evidence by
      reporting atypical activation in the same brain regions during response
      inhibition, working memory, and emotion processing. There are, however, several
      limitations of the abuse research literature which are discussed, most
      prominently the lack of control for co-morbid psychiatric disorders, which make
      it difficult to disentangle which of the above effects are due to maltreatment,
      the associated psychiatric conditions or a combination or interaction between
      both. Overall, the better controlled studies that show a direct correlation
      between childhood abuse and brain measures suggest that the most prominent
      deficits associated with early childhood abuse are in the function and structure
      of lateral and ventromedial fronto-limbic brain areas and networks that mediate
      behavioral and affect control. Future, large scale multimodal neuroimaging
      studies in medication-naive subjects, however, are needed that control for
      psychiatric co-morbidities in order to elucidate the structural and functional
      brain sequelae that are associated with early environmental adversity,
      independently of secondary co-morbid conditions.

PMID- 22457646
TI  - Meditation-induced changes in high-frequency heart rate variability predict
      smoking outcomes.
AB  - BACKGROUND: High-frequency heart rate variability (HF-HRV) is a measure of
      parasympathetic nervous system (PNS) output that has been associated with
      enhanced self-regulation. Low resting levels of HF-HRV are associated with
      nicotine dependence and blunted stress-related changes in HF-HRV are associated
      with decreased ability to resist smoking. Meditation has been shown to increase
      HF-HRV. However, it is unknown whether tonic levels of HF-HRV or acute changes in
      HF-HRV during meditation predict treatment responses in addictive behaviors such
      as smoking cessation. PURPOSE: To investigate the relationship between HF-HRV and
      subsequent smoking outcomes. METHODS: HF-HRV during resting baseline and during
      mindfulness meditation was measured within two weeks of completing a 4-week
      smoking cessation intervention in a sample of 31 community participants. Self
      report measures of smoking were obtained at a follow up 17-weeks after the
      initiation of treatment. RESULTS: Regression analyses indicated that individuals
      exhibiting acute increases in HF-HRV from resting baseline to meditation smoked
      fewer cigarettes at follow-up than those who exhibited acute decreases in HF-HRV
      (b = -4.89, p = 0.008). CONCLUSION: Acute changes in HF-HRV in response to
      meditation may be a useful tool to predict smoking cessation treatment response.

PMID- 22457647
TI  - Is lactate a volume transmitter of metabolic states of the brain?
AB  - We present the perspective that lactate is a volume transmitter of cellular
      signals in brain that acutely and chronically regulate the energy metabolism of
      large neuronal ensembles. From this perspective, we interpret recent evidence to
      mean that lactate transmission serves the maintenance of network metabolism by
      two different mechanisms, one by regulating the formation of cAMP via the lactate
      receptor GPR81, the other by adjusting the NADH/NAD(+) redox ratios, both linked
      to the maintenance of brain energy turnover and possibly cerebral blood flow. The
      role of lactate as mediator of metabolic information rather than metabolic
      substrate answers a number of questions raised by the controversial oxidativeness
      of astrocytic metabolism and its contribution to neuronal function.

PMID- 22457648
TI  - Physiological antioxidative network of the bilirubin system in aging and age
      related diseases.
AB  - Oxidative stress is detrimental to life process and is particularly responsible
      for aging and age-related diseases. Thus, most organisms are well equipped with a
      spectrum of biological defense mechanisms against oxidative stress. The major
      efficient antioxidative mechanism is the glutathione system, operating a redox
      cycling mechanism for glutathione utilization, which consists of glutathione and
      its peroxidase and reductase. However, this system is mainly effective for
      hydrophilic oxidants, while lipophilic oxidants require another scavenging
      system. Since many age-related pathological conditions are related to lipid
      peroxidation, especially in association with the aging process, the physiological
      role of the scavenging system for lipophilic oxidants should be considered. In
      this regard, the biliverdin to bilirubin conversion pathway, via biliverdin
      reductase (BVR), is suggested to be another major protective mechanism that
      scavenges lipophilic oxidants because of the lipophilic nature of bilirubin. The
      efficiency of this bilirubin system might be potentiated by operation of the
      intertwined bicyclic systems of the suggested redox metabolic cycle of biliverdin
      and bilirubin and the interactive control cycle of BVR and heme oxygenase. In
      order to combat oxidative stress, both antioxidative systems against hydrophilic
      and lipophilic oxidants are required to work cooperatively. In this regard, the
      roles of the bilirubin system in aging and age-related diseases are reassessed in
      this review, and their interacting networks are evaluated.

PMID- 22457649
TI  - Phenotypic and functional heterogeneity of macrophages and dendritic cell subsets
      in the healthy and atherosclerosis-prone aorta.
AB  - Atherosclerosis continues to be the leading cause of cardiovascular disease.
      Development of atherosclerosis depends on chronic inflammation in the aorta and
      multiple immune cells are involved in this process. Importantly, resident
      macrophages and dendritic cells (DCs) are present within the healthy aorta, but
      the functions of these cells remain poorly characterized. Local inflammation
      within the aortic wall promotes the recruitment of monocytes and DC precursors to
      the aorta and micro-environmental factors direct the differentiation of these
      emigrated cells into multiple subsets of macrophages and DCs. Recent data suggest
      that several populations of macrophages and DCs can co-exist within the aorta.
      Although the functions of M1, M2, Mox, and M4 macrophages are well characterized
      in vitro, there is a limited set of data on the role of these populations in
      atherogenesis in vivo. Recent studies on the origin and the potential role of
      aortic DCs provide novel insights into the biology of aortic DC subsets and
      prospective mechanisms of the immune response in atherosclerosis. This review
      integrates the results of experiments analyzing heterogeneity of DCs and
      macrophage subsets in healthy and diseased vessels and briefly discusses the
      known and potential functions of these cells in atherogenesis.

PMID- 22457650
TI  - Generation and applications of human pluripotent stem cells induced into neural
      lineages and neural tissues.
AB  - Human pluripotent stem cells (hPSCs) represent a new and exciting field in modern
      medicine, now the focus of many researchers and media outlets. The hype is well
      earned because of the potential of stem cells to contribute to disease modeling,
      drug screening, and even therapeutic approaches. In this review, we focus first
      on neural differentiation of these cells. In a second part we compare the various
      cell types available and their advantages for in vitro modeling. Then we provide
      a "state-of-the-art" report about two major biomedical applications: (1) the drug
      and toxicity screening and (2) the neural tissue replacement. Finally, we made an
      overview about current biomedical research using differentiated hPSCs.

PMID- 22457651
TI  - microRNA are Central Players in Anti- and Profibrotic Gene Regulation during
      Liver Fibrosis.
AB  - MicroRNA (miRNA) are small non-coding RNA molecules that posttranscriptionally
      effect mRNA stability and translation by targeting the 3'-untranslated region (3'
      UTR) of various transcripts. Thus, dysregulation of miRNA affects a wide range of
      cellular processes such as cell proliferation and differentiation involved in
      organ remodeling processes. Divergent miRNA patterns were observed during chronic
      liver diseases of various etiologies. Chronic liver diseases result in
      uncontrolled scar formation ending up in liver fibrosis or even cirrhosis. Since
      it has been shown that miR-29 dysregulation is involved in synthesis of
      extracellular matrix proteins, miR-29 is of special interest. The importance of
      miR-29 in hepatic collagen homeostasis is underlined by in vivo data showing that
      experimental severe fibrosis is associated with a prominent miR-29 decrease. The
      loss of miR-29 is due to the response of hepatic stellate cells to exposure to
      the profibrogenic mediators TGF-beta and PDGF-BB. Several putative binding sites
      for the Smad proteins and the Ap1 complex are located in the miR-29 promoter,
      which are suggested to mediate miR-29 decrease in fibrosis. Other miRNA are
      highly increased after profibrogenic stimulation, such as miR-21. miR-21 is
      transcriptionally upregulated in response to Smad-3 rather than Smad-2 activation
      after TGF-beta stimulation. In addition, TGF-beta promotes miR-21 expression by
      formation of a microprocessor complex containing Smad proteins. Elevated miR-21
      may then act as a profibrogenic miRNA by its repression of the TGF-beta
      inhibitory Smad-7 protein.

PMID- 22457652
TI  - Differential Regulation of TGF-beta/Smad Signaling in Hepatic Stellate Cells
      between Acute and Chronic Liver Injuries.
AB  - Current evidence suggests that regulation of extracellular matrix (ECM)
      accumulation by fibrogenic transforming growth factor (TGF)-beta and platelet
      derived growth factor (PDGF) signals involves different mechanisms in acute and
      chronic liver injuries, even though hepatic stellate cells (HSC) are the
      principal effecter in both cases. As a result of chronic liver damage, HSC
      undergo progressive activation to become myofibroblasts (MFB)-like cells. Our
      current review will discuss the differential regulation of TGF-beta signaling
      between HSC and MFB in vitro and in vivo. Smad proteins, which convey signals
      from TGF-beta receptors to the nucleus, have intermediate linker regions between
      conserved Mad-homology (MH) 1 and MH2 domains. TGF-beta type I receptor and Ras
      associated kinases differentially phosphorylate Smad2 and Smad3 to create COOH
      terminally (C), linker (L), or dually (L/C) phosphorylated (p) isoforms. After
      acute liver injury, TGF-beta and PDGF synergistically promote collagen synthesis
      in the activated HSC via pSmad2L/C and pSmad3L/C pathways. To avoid unlimited ECM
      deposition, Smad7 induced by TGF-beta negatively regulates the fibrogenic TGF
      beta signaling. In contrast, TGF-beta and PDGF can transmit the fibrogenic
      pSmad2L/C and mitogenic pSmad3L signals in MFB throughout chronic liver injury,
      because Smad7 cannot be induced by the pSmad3L pathway. This lack of Smad7
      induction might lead to constitutive fibrogenesis in MFB, which eventually
      develop into accelerated liver fibrosis.

PMID- 22457653
TI  - Pest insect olfaction in an insecticide-contaminated environment: info-disruption
      or hormesis effect.
AB  - Most animals, including pest insects, live in an "odor world" and depend strongly
      on chemical stimuli to get information on their biotic and abiotic environment.
      Although integrated pest management strategies including the use of insect growth
      regulators (IGRs) are increasingly developed, most insect pest treatments rely on
      neurotoxic chemicals. These molecules are known to disrupt synaptic transmission,
      affecting therefore sensory systems. The wide-spread use of neurotoxic
      insecticides and the growing use of IGRs result in residual accumulation of low
      concentrations in the environment. These insecticide residues could act as an
      "info-disruptor" by modifying the chemical communication system, and therefore
      decrease chances of reproduction in target insects. However, residues can also
      induce a non-expected hormesis effect by enhancing reproduction abilities. Low
      insecticide doses might thus induce adaptive processes in the olfactory pathway
      of target insects, favoring the development of resistance. The effect of
      sublethal doses of insecticides has mainly been studied in beneficial insects
      such as honeybees. We review here what is known on the effects of sublethal doses
      of insecticides on the olfactory system of insect pests.

PMID- 22457655
TI  - Tools to support interpreting multiple regression in the face of
      multicollinearity.
AB  - While multicollinearity may increase the difficulty of interpreting multiple
      regression (MR) results, it should not cause undue problems for the knowledgeable
      researcher. In the current paper, we argue that rather than using one technique
      to investigate regression results, researchers should consider multiple indices
      to understand the contributions that predictors make not only to a regression
      model, but to each other as well. Some of the techniques to interpret MR effects
      include, but are not limited to, correlation coefficients, beta weights,
      structure coefficients, all possible subsets regression, commonality
      coefficients, dominance weights, and relative importance weights. This article
      will review a set of techniques to interpret MR effects, identify the elements of
      the data on which the methods focus, and identify statistical software to support
      such analyses.

PMID- 22457654
TI  - Epilepsy as a neurodevelopmental disorder.
AB  - Epilepsy is characterized by spontaneous recurrent seizures and comprises a
      diverse group of syndromes with different etiologies. Epileptogenesis refers to
      the process whereby the brain becomes epileptic and can be related to several
      factors, such as acquired structural brain lesions, inborn brain malformations,
      alterations in neuronal signaling, and defects in maturation and plasticity of
      neuronal networks. In this review, we will focus on alterations of brain
      development that lead to an hyperexcitability phenotype in adulthood, providing
      examples from both animal and human studies. Malformations of cortical
      development (including focal cortical dysplasia, lissencephaly, heterotopia, and
      polymicrogyria) are frequently epileptogenic and result from defects in cell
      proliferation in the germinal zone and/or impaired neuronal migration and
      differentiation. Delayed or reduced arrival of inhibitory interneurons into the
      cortical plate is another possible cause of epileptogenesis. GABAergic neurons
      are generated during early development in the ganglionic eminences, and failure
      to pursue migration toward the cortex alters the excitatory/inhibitory balance
      resulting in aberrant network hyperexcitability. More subtle defects in the
      developmental assembly of excitatory and inhibitory synapses are also involved in
      epilepsy. For example, mutations in the presynaptic proteins synapsins and SNAP
      25 cause derangements of synaptic transmission and plasticity which underlie
      appearance of an epileptic phenotype. Finally, there is evidence that defects in
      synapse elimination and remodeling during early "critical periods" can trigger
      hyperexcitability later in life. Further clarification of the developmental
      pathways to epilepsy has important implications for disease prevention and
      therapy.

PMID- 22457656
TI  - Developing representations of compound stimuli.
AB  - Classification based on multiple dimensions of stimuli is usually associated with
      similarity-based representations, whereas uni-dimensional classifications are
      associated with rule-based representations. This paper studies classification of
      stimuli and category representations in school-aged children and adults when
      learning to categorize compound, multi-dimensional stimuli. Stimuli were such
      that both similarity-based and rule-based representations would lead to correct
      classification. This allows testing whether children have a bias for formation of
      similarity-based representations. The results are at odds with this expectation.
      Children use both uni-dimensional and multi-dimensional classification, and the
      use of both strategies increases with age. Multi-dimensional classification is
      best characterized as resulting from an analytic strategy rather than from
      procedural processing of overall-similarity. The conclusion is that children are
      capable of using complex rule-based categorization strategies that involve the
      use of multiple features of the stimuli. The main developmental change concerns
      the efficiency and consistency of the explicit learning system.

PMID- 22457657
TI  - Gesture facilitates the syntactic analysis of speech.
AB  - Recent research suggests that the brain routinely binds together information from
      gesture and speech. However, most of this research focused on the integration of
      representational gestures with the semantic content of speech. Much less is known
      about how other aspects of gesture, such as emphasis, influence the
      interpretation of the syntactic relations in a spoken message. Here, we
      investigated whether beat gestures alter which syntactic structure is assigned to
      ambiguous spoken German sentences. The P600 component of the Event Related Brain
      Potential indicated that the more complex syntactic structure is easier to
      process when the speaker emphasizes the subject of a sentence with a beat. Thus,
      a simple flick of the hand can change our interpretation of who has been doing
      what to whom in a spoken sentence. We conclude that gestures and speech are
      integrated systems. Unlike previous studies, which have shown that the brain
      effortlessly integrates semantic information from gesture and speech, our study
      is the first to demonstrate that this integration also occurs for syntactic
      information. Moreover, the effect appears to be gesture-specific and was not
      found for other stimuli that draw attention to certain parts of speech, including
      prosodic emphasis, or a moving visual stimulus with the same trajectory as the
      gesture. This suggests that only visual emphasis produced with a communicative
      intention in mind (that is, beat gestures) influences language comprehension, but
      not a simple visual movement lacking such an intention.

PMID- 22457658
TI  - On the utilization of social animals as a model for social robotics.
AB  - Social robotics is a thriving field in building artificial agents. The
      possibility to construct agents that can engage in meaningful social interaction
      with humans presents new challenges for engineers. In general, social robotics
      has been inspired primarily by psychologists with the aim of building human-like
      robots. Only a small subcategory of "companion robots" (also referred to as
      robotic pets) was built to mimic animals. In this opinion essay we argue that all
      social robots should be seen as companions and more conceptual emphasis should be
      put on the inter-specific interaction between humans and social robots. This view
      is underlined by the means of an ethological analysis and critical evaluation of
      present day companion robots. We suggest that human-animal interaction provides a
      rich source of knowledge for designing social robots that are able to interact
      with humans under a wide range of conditions.

PMID- 22457659
TI  - Perception of words and pitch patterns in song and speech.
AB  - THIS FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY EXAMINES SHARED AND DISTINCT
      CORTICAL AREAS INVOLVED IN THE AUDITORY PERCEPTION OF SONG AND SPEECH AT THE
      LEVEL OF THEIR UNDERLYING CONSTITUENTS: words and pitch patterns. Univariate and
      multivariate analyses were performed to isolate the neural correlates of the word
      and pitch-based discrimination between song and speech, corrected for rhythmic
      differences in both. Therefore, six conditions, arranged in a subtractive
      hierarchy were created: sung sentences including words, pitch and rhythm; hummed
      speech prosody and song melody containing only pitch patterns and rhythm; and as
      a control the pure musical or speech rhythm. Systematic contrasts between these
      balanced conditions following their hierarchical organization showed a great
      overlap between song and speech at all levels in the bilateral temporal lobe, but
      suggested a differential role of the inferior frontal gyrus (IFG) and
      intraparietal sulcus (IPS) in processing song and speech. While the left IFG
      coded for spoken words and showed predominance over the right IFG in prosodic
      pitch processing, an opposite lateralization was found for pitch in song. The IPS
      showed sensitivity to discrete pitch relations in song as opposed to the gliding
      pitch in speech. Finally, the superior temporal gyrus and premotor cortex coded
      for general differences between words and pitch patterns, irrespective of whether
      they were sung or spoken. Thus, song and speech share many features which are
      reflected in a fundamental similarity of brain areas involved in their
      perception. However, fine-grained acoustic differences on word and pitch level
      are reflected in the IPS and the lateralized activity of the IFG.

PMID- 22457660
TI  - Biotechnology and pasta-making: lactic Acid bacteria as a new driver of
      innovation.
AB  - Cereals-derived foods represent a key constituent in the diet of many
      populations. In particular, pasta is consumed in large quantities throughout the
      world in reason of its nutritive importance, containing significant amounts of
      complex carbohydrates, proteins, B-vitamins, and iron. Lactic acid bacteria (LAB)
      are a heterogeneous group of bacteria that play a key role in the production of
      fermented foods and beverages with high relevance for human and animal health. A
      wide literature testifies the multifaceted importance of LAB biotechnological
      applications in cereal-based products. Several studies focused on LAB isolation
      and characterization in durum wheat environment, in some cases with preliminary
      experimental applications of LAB in pasta-making. In this paper, using sourdough
      as a model, we focus on the relevant state-of-art to introduce a LAB-based
      biotechnological step in industrial pasta-making, a potential world driver of
      innovation that might represent a cutting-edge advancement in pasta production.

PMID- 22457661
TI  - Dissolved phosphorus pools and alkaline phosphatase activity in the euphotic zone
      of the Western north pacific ocean.
AB  - We measured pools of dissolved phosphorus (P), including dissolved inorganic P
      (DIP), dissolved organic P (DOP) and alkaline phosphatase (AP)-hydrolyzable
      labile DOP (L-DOP), and kinetic parameters of AP activity (APA) in the euphotic
      zone in the western North Pacific Ocean. Samples were collected from one coastal
      station in Sagami Bay, Japan, and three offshore stations between the North
      Pacific subtropical gyre (NPSG) and the Kuroshio region. Although DIP
      concentrations in the euphotic zone at all stations were equally low, around the
      nominal method detection limit of 20 nmol L(-1), chlorophyll a (Chl a)
      concentrations were one order of magnitude greater at the coastal station. DOP
      was the dominant P pool, comprising 62-92% of total dissolved P at and above the
      Chl a maximum layer (CML). L-DOP represented 22-39% of the total DOP at the
      offshore stations, whereas it accounted for a much higher proportion (about 85%)
      in the coastal surface layers. Significant correlations between maximum potential
      AP hydrolysis rates and DIP concentrations or bacterial cell abundance in the
      offshore euphotic zone suggest that major APA in the oligotrophic surface ocean
      is from bacterial activity and regulated largely by DIP availability. Although
      the range of maximum potential APA was comparable among the environmental
      conditions, the in situ hydrolysis rate of L-DOP in the coastal station was 10
      times those in the offshore stations. L-DOP turnover time at the CML ranged from
      4.5 days at the coastal station to 84.4 days in the NPSG. The ratio of the APA
      half-saturation constant to the ambient L-DOP concentration decreased markedly
      from the NPSG to the coastal station. There were substantial differences in the
      rate and efficiency of DOP remineralization and its contribution as the potential
      P source between the low-phosphate/high-biomass coastal ecosystem and the low
      phosphate/low biomass oligotrophic ocean.

PMID- 22457662
TI  - Enhancing effects on vacuole-targeting fungicidal activity of amphotericin B.
AB  - Invasive fungal infections are major threats for immunocompromised patients as
      well as for those undergoing cancer chemotherapy. Amphotericin B (AmB), a
      classical antifungal drug with a polyene macrolide structure, is widely used for
      the control of serious fungal infections. However, the clinical use of this
      antifungal drug is limited by its side effects and the emergence of drug
      resistant strains. AmB lethality has been generally attributed to alterations in
      plasma membrane ion permeability due to its specific binding to plasma membrane
      ergosterol. Recent studies with Saccharomyces cerevisiae and Candida albicans
      reveal the vacuole disruptive action as another cause of AmB lethality on the
      basis of marked amplification of its activity in combination with allicin, an
      allyl-sulfur compound from garlic. The enhancing effect of allicin is dependent
      on the inhibition of ergosterol-trafficking from the plasma membrane to the
      vacuole membrane, which is considered to be a cellular response to protect
      against disintegration of the vacuole membrane. The polyol macrolide niphimycin
      (NM) also possesses vacuole-targeting fungicidal activity, which is greater than
      that of AmB and nystatin. The alkyl side chain attached to the macrolide ring of
      NM is considered to possess an allicin-like inhibitory effect on the
      intracellular trafficking of ergosterol. The vacuole-targeting fungicidal
      activity was additionally detected with a bactericidal cyclic peptide polymyxin B
      (PMB), and was markedly enhanced when administered together with allicin,
      monensin, or salinomycin. The synergistic fungicidal activities of AmB and
      allicin may have significant implications for the development of vacuole
      targeting chemotherapy against fungal infections.

PMID- 22457664
TI  - The effects of statins on blood pressure: current knowledge and future
      perspectives.

PMID- 22457665
TI  - Vitamin D: a novel player in endothelial function and dysfunction.

PMID- 22457663
TI  - Genetics of recurrent miscarriage: challenges, current knowledge, future
      directions.
AB  - Recurrent miscarriage (RM) occurs in 1-3% of couples aiming at childbirth. Due to
      multifactorial etiology the clinical diagnosis of RM varies. The design of
      genetic/"omics" studies to identify genes and biological mechanisms involved in
      pathogenesis of RM has challenges as there are several options in defining the
      study subjects (female patient and/or couple with miscarriages, fetus/placenta)
      and controls. An ideal study would attempt a trio-design focusing on both
      partners as well as pregnancies of the couple. Application of genetic association
      studies focusing on pre-selected candidate genes with potential pathological
      effect in RM show limitations. Polymorphisms in ~100 genes have been investigated
      and association with RM is often inconclusive or negative. Also, implication of
      prognostic molecular diagnostic tests in clinical practice exhibits
      uncertainties. Future directions in investigating biomolecular risk factors for
      RM rely on integrating alternative approaches (SNPs, copy number variations,
      gene/protein expression, epigenetic regulation) in studies of single genes as
      well as whole-genome analysis. This would be enhanced by collaborative network
      between research centers and RM clinics.

PMID- 22457666
TI  - The clinical benefit of implementing guidelines in cardiovascular disease
      prevention in real world settings.

PMID- 22457667
TI  - Right heart perforation by pacemaker leads.

PMID- 22457668
TI  - Coarctation of the aorta.

PMID- 22457669
TI  - Effects of 4-week administration of simvastatin in different doses on heart rate
      and blood pressure after metoprolol injection in normocholesterolaemic and
      normotensive rats.
AB  - INTRODUCTION: Statins and beta1-adrenergic antagonists are well established in
      cardiovascular events therapy and prevention. The previous study showed that
      statins might impact on beta-adrenergic signalling and blood pressure in a dose
      dependent manner. The aim of the study was to evaluate the impact of 4-week
      administration of simvastatin given at different doses on the heart rate and
      blood pressure after injection of metoprolol in rats. MATERIAL AND METHODS: The
      experiments were performed in normocholesterolaemic and normotensive Wistar rats.
      Rats received simvastatin in doses of 1, 10 and 20 mg/kg body weight (bw) for 4
      weeks. The control group received 0.2% methylcellulose. For the further
      estimation of the heart rate and blood pressure, metoprolol at 5 mg/kg bw or 0.9%
      NaCl was injected intraperitoneally. RESULTS: Simvastatin at doses of 1, 10 and
      20 mg/kg bw did not influence the heart rate or blood pressure as compared to the
      control group. Metoprolol injection statistically significantly decreased the
      heart rate (439.29+/-14.03 min(-1) vs. 374.41+/-13.32 min(-1); p<0.05). In rats
      receiving simvastatin during the 4-week period after metoprolol injection, heart
      rate and blood pressure (mean, systolic, diastolic) were similar as compared to
      the group receiving metoprolol alone. CONCLUSIONS: Simvastatin administration
      during a 4-week period in different doses did not influence the heart rate or
      blood pressure after metoprolol injection in normocholesterolaemic and
      normotensive rats.

PMID- 22457670
TI  - The effects of palm vitamin E on stress hormone levels and gastric lesions in
      stress-induced rats.
AB  - INTRODUCTION: This study examines the effects of palm vitamin E (PVE) or alpha
      tocopherol (alpha-TF) supplementation on adrenocorticotropin hormone (ACTH),
      corticosterone and gastric lesions in rats exposed to water-immersion restraint
      stress (WIRS). MATERIAL AND METHODS: Sixty male Sprague-Dawley rats (200-250 g)
      were divided into three groups. Group I: 20 rats as a control group were given a
      normal diet. Group II: 20 rats received oral supplementation of PVE at 60 mg/kg
      body weight. Group III: 20 rats received oral supplementation of alpha-TF at 60
      mg/kg body weight. After the treatment period of 28 days, each group was further
      subdivided into two groups: 10 rats not exposed to stress, and the other 10 rats
      subjected to WIRS for 3.5 h. Blood samples were taken to measure the ACTH and
      corticosterone levels. The rats were then sacrificed and the stomach excised and
      opened along the greater curvature and examined for lesions. RESULTS: Rats
      exposed to WIRS had lesions in their stomach mucosa. Our findings showed that
      dietary supplementation of PVE or alpha-TF was able to reduce gastric lesions
      significantly in comparison to the stressed controls. The WIRS increased plasma
      ACTH and corticosterone significantly. Palm vitamin E and alpha-TF treatments
      reduced these parameters significantly compared to the stressed controls.
      CONCLUSIONS: Supplementation with either PVE or alpha-TF reduces the formation of
      gastric lesions, probably by inhibiting the elevation of ACTH and corticosterone
      levels induced by stress.

PMID- 22457671
TI  - Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and
      osteo-differentiation potential.
AB  - INTRODUCTION: Aging people's bone regeneration potential is always impaired. Bone
      marrow stromal cells (MSCs) contain progenitors of osteoblasts. Donor age may
      affect MSCs' proliferation and differentiation potential, but the genomic base is
      still unknown. Due to recent research's indication that a core circadian
      component, brain and muscle ARNT-like 1 protein (BMAL1), has a role in premature
      aging, we investigated the normal aging mechanism in mice with their MSCs and
      Bmal1 gene/protein level. MATERIAL AND METHODS: 1, 6 and 16 month old C57BL/6
      mice were used and the bone marrow stromal cells were gained and cultured at
      early passage. Bmal1 gene and protein level were detected in these cells. Marrow
      stromal cells were also induced to differentiate to osteoblasts or adipocytes.
      Three groups of mice MSCs were compared on proliferation by flow cytometry, on
      cell senescence by SA-beta-gal expression and after osteo-induction on osteogenic
      potential by the expression of osterix (Osx), alkaline phosphatase (ALP) and
      osteocalcin (OCN). RESULTS: Bmal1 gene and protein level as well as S-phase
      fraction of the cell cycle decreased in MSCs along with the aging process. At the
      same time, SA-beta-gal+ levels increased, especially in the aged mice MSCs. When
      induced to be osteogenic, Osx gene expression and ALP activity declined in the
      mid-age and aged mice MSCs, while OCN protein secretion deteriorated in the aged
      mice MSCs. CONCLUSIONS: These findings demonstrate that mouse MSCs changed with
      their proliferation and osteo-differentiation abilities at different aging
      stages, and that Bmal1 is related to the normal aging process in MSCs.

PMID- 22457672
TI  - Antimicrobial-resistant Klebsiella species isolated from free-range chicken
      samples in an informal settlement.
AB  - INTRODUCTION: Sub-therapeutic doses of antimicrobial agents are administered
      routinely to poultry to aid growth and to prevent disease, with prolonged
      exposure often resulting in bacterial resistance. Crossover of antibiotic
      resistant bacteria from poultry to humans poses a risk to human health. MATERIAL
      AND METHODS: In this study, 17 chicken samples collected from a vendor operating
      in an informal settlement in the Cape Town Metropolitan area, South Africa were
      screened for antimicrobial-resistant Gram-negative bacilli using the Kirby Bauer
      disk diffusion assay. RESULTS: IN TOTAL, SIX ANTIBIOTICS WERE SCREENED:
      ampicillin, ciprofloxacin, gentamicin, nalidixic acid, tetracycline and
      trimethoprim. Surprisingly, Klebsiella ozaenae was identified in 96 and K.
      rhinoscleromatis in 6 (n=102) of the samples tested. Interestingly, ~40% of the
      isolated Klebsiella spp. showed multiple resistance to at least three of the six
      antibiotics tested. CONCLUSIONS: Klebsiella ozaenae and K. rhinoscleromatis cause
      clinical chronic rhinitis and are almost exclusively associated with people
      living in areas of poor hygiene.

PMID- 22457673
TI  - The influence of extracts from Peucedanum salinum on the replication of
      adenovirus type 5.
AB  - INTRODUCTION: The aim of the study was to examine the cytotoxicity and evaluate
      the antiviral and virucidal activity of methanol and methanol/H(2)O extracts from
      the herb of Peucedanum salinum. Plants belonging to the genus Peucedanum
      (Apiaceae family) have been used in traditional medicine for a long time.
      MATERIAL AND METHODS: The examination of the cytotoxicity of the extracts in the
      concentrations of 0.1, 0.2, 0.5, 1, 2, 4 mg/ml was carried out on the cell
      culture line HEK-293. Cytotoxicity of the examined extracts was measured by the
      colorimetric MTT (tetrazolium) method. After determination of the highest non
      toxic concentration of examined extracts, antiviral and virucidal activity
      against adenovirus type 5 (Adenoviridae) was established. RESULTS: The non-toxic
      doses were as follows: 1 mg/ml of methanol extract and 2 mg/ml of methanol/H(2)O
      extract (1 : 1 v/v). Antiviral activity was observed for the methanol extract of
      Peucedanum salinum in concentrations of 0.5 and 1 mg/ml. The extract caused the
      decrease of titre of the virus by 2 log and 1.33 log, respectively. The
      methanol/H(2)O extract (1 : 1 v/v) decreased the titre of the virus by 1.33 log
      and 1.5 log in concentrations of 1 and 2 mg/ml, respectively. The examined
      extracts had no virucidal activity against adenovirus type 5. CONCLUSIONS: The
      examined extract is a new, potentially active source of active substances
      possessing antiviral activity and further studies are needed.

PMID- 22457674
TI  - 25-Hydroxy vitamin D levels and endothelial vasodilator function in normotensive
      women.
AB  - INTRODUCTION: Vitamin D was shown to be related to endothelial function and blood
      pressure. Reactive hyperaemia index (RHI) measurement by pulse arterial tonometry
      is a new method to evaluate vasodilator function of endothelium. We aimed to
      evaluate the relationship between vitamin D levels and RHI in women. MATERIAL AND
      METHODS: We enrolled 56 normotensive, nonsmoker, normolipidemic and normoglycemic
      women, (23 with 25-OH-vitamin D levels>20 ug/l, and 33 with values lower than 20
      ug/l). The cardiologist who was blind for vitamin D results executed measurements
      by pulse arterial tonometry. The measurement was performed on the lying patient
      with pre- and post-occlusion measurements of RHI by digital sensors placed on
      each index finger, by 5 min intervals. Pulse amplitudes were recorded, pre
      occlusion and post-occlusion ratio was compared by the software of device.
      Stepwise linear regression and multiple regression analyses were performed to
      evaluate predictors of endothelial function. RESULTS: The low vitamin D group had
      a lower RHI value than the normal vitamin D group (p = 0.042). In regression
      analysis, positive predictors of RHI were serum 25-OHD (beta = 0.401; 95% CI
      0.010-0.042, p = 0.002), serum albumin (beta = 0.315; 95% CI 0.286-2.350, p =
      0.013), and, inversely, serum calcium (beta = -0.247; 95% CI (-1.347)-(-0.010), p
      = 0.047). CONCLUSIONS: Serum 25-hydroxy vitamin D was significantly related to
      endothelial functions measured as RHI, even in healthy non-smoker women.

PMID- 22457675
TI  - The impact of statin therapy on long-term cardiovascular outcomes in an
      outpatient cardiology practice.
AB  - INTRODUCTION: Statins reduce coronary events in patients with coronary artery
      disease. MATERIAL AND METHODS: Chart reviews were performed in 305 patients (217
      men and 88 women, mean age 74 years) not treated with statins during the first
      year of being seen in an outpatient cardiology practice but subsequently treated
      with statins. Based on the starting date of statins use, the long-term outcomes
      of myocardial infarction (MI), percutaneous coronary intervention (PCI), and
      coronary artery bypass graft surgery (CABGs) before and after statin use were
      compared. RESULTS: Mean follow-up was 65 months before statins use and 66 months
      after statins use. Myocardial infarction occurred in 31 of 305 patients (10%)
      before statins, and in 13 of 305 patients (4%) after statins (p < 0.01).
      Percutaneous coronary intervention had been performed in 66 of 305 patients (22%)
      before statins and was performed in 41 of 305 patients (13%) after statins (p <
      0.01). Coronary artery bypass graft surgery had been performed in 56 of 305
      patients (18%) before statins and in 20 of 305 patients (7%) after statins (p <
      0.001). Stepwise logistic regression showed statins use was an independent risk
      factor for MI (odds ratio = 0.0207, 95% CI, 0.0082-0.0522, p < 0.0001), PCI (odds
      ratio = 0.0109, 95% CI, 0.0038-0.0315, p < 0.0001) and CABGs (odds ratio =
      0.0177, 95% CI = 0.0072-0.0431, p < 0.0001) CONCLUSIONS: Statins use in an
      outpatient cardiology practice reduces the incidence of MI, PCI, and CABGs.

PMID- 22457676
TI  - Reduction in atherosclerotic events: a retrospective study in an outpatient
      cardiology practice.
AB  - INTRODUCTION: Although atherosclerotic disease cannot be cured, risk of recurrent
      events can be reduced by application of evidence-based treatment protocols
      involving aspirin, beta blockers, angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers, and statin medications. We studied atherosclerotic
      event rates in a patient population treated before and after the development of
      aggressive risk factor reduction treatment protocols. MATERIAL AND METHODS: We
      performed a retrospective chart review of patients presenting for follow-up
      treatment of coronary artery disease in a community cardiology practice,
      comparing atherosclerotic event rates and medication usage in a 2-year treatment
      period prior to 2002 and a 2-year period in 2005-2008. Care was provided in both
      the early and later eras by 7 board-certified cardiologists in a suburban
      cardiology practice. Medication usage was compared in both treatment eras. The
      primary outcome was a composite event rate of myocardial infarction,
      cerebrovascular events, and coronary interventions. RESULTS: Three hundred and
      fifty-seven patients were studied, with a follow-up duration of 12.1 (+/-3.5)
      years. There were 132 composite events in 104 patients (29.1%) in the early era
      compared to 40 events in 33 patients (9.2%) in the later era (p < 0.0001). From
      the early to the later eras, there was an increase in use of beta-blockers (66%
      to 83%, p < 0.0001), angiotensin-converting enzyme inhibitors or angiotensin
      receptor blockers (34% to 80%, p < 0.0001), and statins (40% to 90%, p < 0.0001).
      CONCLUSIONS: Application of aggressive evidence-based medication protocols for
      treatment of atherosclerosis is associated with a significant decrease in
      atherosclerotic events or need for coronary intervention.

PMID- 22457677
TI  - Changes in left ventricular ejection fraction and coronary flow reserve after
      coronary microembolization.
AB  - INTRODUCTION: Although coronary microembolization (CME) is a frequent phenomenon
      in patients undergoing percutaneous coronary intervention, few data are available
      on the changes in left ventricular ejection fraction (LVEF) and coronary flow
      reserve (CFR) after CME. MATERIAL AND METHODS: In this study, six miniature swine
      of either sex (body weight 21-25 kg) were used to prepare a CME model. After
      coronary angiography, 1.2 * 10(5) microspheres (42 um) were selectively infused
      into the left anterior descending artery via an infusion catheter. Left
      ventricular ejection fraction was evaluated using transthoracic echocardiography;
      myocardial blood flow was measured using coloured microspheres; and CFR and
      coronary pressure were measured using Doppler and a pressure wire. RESULTS: Left
      ventricular ejection fraction was 0.77 +/-0.08 at baseline, 0.69 +/-0.08 at 2 h,
      0.68 +/-0.08 at 6 h, and 0.76 +/-0.06 at 1 week (2 h vs. baseline p < 0.05; 6 h
      vs. baseline p < 0.01). After CME, left ventricular end systolic volume (LVESV)
      and end diastolic volume (LVEDV) were significant larger 1 week later (p < 0.01
      for both), while CFR was significantly reduced at 6 h (1.24 +/-0.10 at 6 h vs.
      1.77 +/-0.30 at baseline, p < 0.01) and myocardial blood flow remained unchanged.
      Serum ET-1 level was significantly higher only at 6 h after CME (6 h vs. baseline
      p < 0.05). CONCLUSIONS: Reduction of CFR and LVEF is significant at 6 h after CME
      and recovers 1 week later with left ventricular dilation.

PMID- 22457678
TI  - Heart perforation in patients with permanent cardiac pacing - pilot personal
      observations.
AB  - INTRODUCTION: Heart perforation is a rare complication of pacemaker
      (PM)/implantable cardioverter-defibrillator (ICD) implantation. MATERIAL AND
      METHODS: In our clinic in 2005-2010, 6 patients with heart perforation were
      hospitalized (3 women, 3 men), mean age 58.6 +/-20.8 years (17 to 73 years). The
      indication to PM/ICD implantation was tachy-brady syndrome in 3 cases, second
      degree atrioventricular block, advanced with losses of consciousness, vaso-vagal
      syndrome type II B with asystole lasting 12 s and recurrent non-sustained
      ventricular tachycardia in 1 patient. We analyzed patient's medical records, X
      rays, echocardiography, computed tomography (CT) and procedure protocols.
      RESULTS: The incidence of heart perforation was 0.09%. Symptoms developed 4 to
      990 days (mean 186.3 +/-394.3) after PM/ICD implantation. The perforation site
      was found in the right atrial wall in 1 cases and the right ventricular wall in 6
      cases. The TTE revealed an accumulation of fluid in the pericardium over 10 mm
      behind the posterior wall of the left ventricle in all patients. The CT scan
      confirmed perforation of the heart chambers (atrium and in 6 cases ventricle). In
      5 cases the whole device was removed by direct traction or percutaneous lead
      extraction with pericardiocentesis when necessary (pericardium drainage in 3
      cases) while in 1 case cardiac surgery was needed. CONCLUSIONS: The perforating
      lead may be removed by direct traction in the operating room with cardiosurgical,
      anesthesiological and echocardiographical backup. In case of the lead perforation
      outside the pericardial sac or its atypical location, cardiac surgery is a safer
      method. The most important diagnostic method remains computed tomography.

PMID- 22457679
TI  - Comparison of mid-term outcomes of carotid artery stenting for moderate versus
      critical stenosis.
AB  - INTRODUCTION: Little is known about the prognosis of moderate versus critical
      carotid stenosis treated by carotid artery stenting (CAS). MATERIAL AND METHODS:
      This was a retrospective analysis of a single-centre registry including 271
      consecutive patients (69 +/-9 years, 87% at high risk for surgery), in whom 308
      procedures were performed. The study included both symptomatic (>= 50% carotid
      artery stenosis) and asymptomatic (>= 70% carotid artery stenosis) patients. The
      primary endpoint was the rate of adverse events during follow-up (range 1-48
      months), defined as all-cause death or stroke. RESULTS: We treated 115 critical
      and 193 moderate stenoses and implanted 318 stents (56% with closed cell design).
      Embolic protection systems were used in 296 cases (96%). The technical success
      rate was 98.2% in the critical stenoses group and 99% in the moderate group (NS).
      During follow-up, the incidence of the primary endpoint was 12.9% (13 pts) in the
      critical stenoses group and 14.7% (25 pts) in the moderate stenoses group
      (estimated 3-year freedom from death/stroke was 0.844 vs. 0.812; log-rank test p
      = 0.983). Left ventricular ejection fraction < 40%, significant contralateral
      carotid artery occlusion or stenosis and renal insufficiency were identified as
      significant predictors of the primary endpoint (p < 0.03). CONCLUSIONS: Carotid
      artery stenting with embolic protection systems in patients at high risk for
      carotid endarterectomy is safe. Patients with initially moderate and critical
      stenoses have an identical mid-term prognosis with regard to death and stroke.

PMID- 22457680
TI  - Prosthetic status and treatment needs for lost masticatory function in
      haemodialysis patients.
AB  - INTRODUCTION: Premature loss of permanent teeth leads to stomatognathic system
      disability. It is a very serious but underrated problem for patients with chronic
      renal failure. The aim of study was analyse the degree of loss of masticatory
      function and number of teeth present for haemodialysis patients, and to define
      patients' needs for prosthetic treatment, which could restore correct occlusal
      condition. MATERIAL AND METHODS: Sixty-nine haemodialysis patients treated at the
      Nephrology and Transplantology Clinic with the Dialysis Centre at the Medical
      University of Bialystok, Poland. We checked: 1) the total number of teeth and
      number of teeth separately for upper and lower jaws, 2) the existing prosthetic
      restorations and 3) the preserved masticatory function. RESULTS: More male than
      female patients were in possession of full dentition.All patients with at least
      28 natural teeth with retained occlusal contacts whilst chewing were males (4;
      10% males; 5.7% of the whole group). There were 15 edentulous patients: 7 males
      (10%) and 8 females (11.5%). Hundered percent of female patients presented with
      various degrees of tooth loss and needed prosthetic treatment. Nearly 70% of
      tested haemodialysis patients did not have a reconstructed masticatory function.
      CONCLUSIONS: The population of haemodialysis patients from the North East part of
      Poland are patients with severe stomatognathic system dysfunctions. It is of
      importance for dentists, as well as nephrologists, to understand the essence of
      the problem, as the general health of a patient cannot be improved without
      ensuring functional comfort of such as important system as the masticatory one.

PMID- 22457681
TI  - Pharmacokinetics of mycophenolic acid and its phenyl glucuronide metabolite in
      kidney transplant recipients with renal impairment.
AB  - INTRODUCTION: The aim of the study was to analyse the influence of renal
      impairment on the pharmacokinetic parameters (PK) of mycophenolic acid (MPA) and
      its glucuronide metabolite (MPAG) in renal transplant recipients. MATERIAL AND
      METHODS: The study included 43 adult patients during the maintenance period (> 6
      months) following renal transplantation, treated with mycophenolate mofetil
      (MMF), calcineurin inhibitors (CNI) (tacrolimus or cyclosporine) and steroids.
      The study compared patients with normal renal function (n = 17; creatinine
      clearance (C(cr)) > 60 ml/min) and with renal impairment (n = 26; C(cr) < 60
      ml/min). Areas under the 4-h curve (AUC(0-4 h)) of MPA and MPAG were determined
      using a validated HPLC method. RESULTS: The renal impairment group showed
      significantly increased AUC(0-4 h) and pre-dose (C(0)) for MPAG compared to
      patients with normal renal function and increased MPA C(0). However, there was no
      significant difference in MPA AUC(0-4 h) between patients with renal impairment
      and patients with normal renal function. In multivariate analysis some MPA and
      MPAG PK parameters were correlated with sex, CNI co-administered and body weight.
      CONCLUSIONS: Although MPAG is an inactive metabolite, its accumulation in
      patients with renal impairment can be unfavourable. The results of our study
      indicate that solely MPA C(0) determination in patients receiving MMF may be
      insufficient in clinical practice because of great inter-patient variability of
      this PK parameter caused mainly by enterohepatic recirculation.

PMID- 22457682
TI  - Hormonal activity in clinically silent adrenal incidentalomas.
AB  - INTRODUCTION: The rapid development of modern imaging techniques, has led to an
      increase in accidentally discovered adrenal masses without clinically apparent
      hormonal abnormalities. Such tumours have been termed "incidentalomas". The
      diagnostic work-up in patients with adrenal incidentalomas is aimed at the
      determination of hormonal activity of the tumour and identification of patients
      with potentially malignant tumours. The aim of our study was a retrospective
      analysis of selected clinical characteristics and hormonal studies in
      accidentally discovered adrenal tumours. MATERIAL AND METHODS: Fourty hundred
      sixty-three patients with serendipitously discovered adrenal masses, diagnosed
      and treated in the Department of Endocrinology and Internal Diseases, Medical
      University of Gdansk as well as in the affiliated Endocrinology Clinic between
      1993 and October of 2009 were included in the analysis. Out of all patients, 245
      were referred for adrenalectomy. RESULTS: We found that clinically "silent"
      tumours often demonstrate subclinical hormonal activity. In our report, increased
      24-h urinary excretion of cortisol correlated positively with tumour size (p <
      0.001). Moreover, a statistical relationship was demonstrated between tumour size
      and serum cortisol concentration assessed in the 1 mg dexamethasone suppression
      test (p < 0.001). Increased values of
      dehydroepiandrosterone/dehydroepiandrosterone sulphate were more often found in
      malignant than in benign tumours (p < 0.01). Urinary concentrations of 17
      ketosteroids correlate positively with diagnosis of adrenocortical cancer (p =
      0.02). CONCLUSIONS: We found that clinically "silent" tumours often demonstrate
      subclinical hormonal activity (subclinical Cushing syndrome, subclinical
      pheochromocytoma, low-symptomatic adrenocortical cancer).

PMID- 22457683
TI  - Correlation between eye and ear symptoms and lack of teeth, bruxism and other
      parafunctions in a population of 1006 patients in 2003-2008.
AB  - INTRODUCTION: Parafunctions (harmful habits) play a crucial role in the formation
      of temporo-mandibular joint (TMJ) dysfunction syndrome with disc displacement.
      Disorder symptoms in temporo-mandibular joints manifest themselves in the eye and
      ear but are usually not associated with the dysfunction of temporo-mandibular
      joints and that might lead to errors in diagnosis. The aim of the study was to
      examine the influence of missing teeth and parafunctions on the occurrence of ear
      and eye symptoms in patients treated in the Department of Prosthodontics of the
      Medical University of Lublin. MATERIAL AND METHODS: The patient group consisted
      of 753 women and 253 men aged 10 to 82 years who had been treated in the
      Department of Prosthodontics, Medical University of Lublin in the years 2003-2008
      due to various symptoms associated with temporo-mandibular joint dysfunction.
      RESULTS: Eye (24.84%, n = 785) and ear (33.38%, n = 785) syndromes occur on
      average more often in patients with parafunctions than without them (15.98%, n =
      219 and 23.29%, n = 219). However, only parafunctions involving tooth contact
      should be taken into consideration when diagnosing eye and ear syndromes. The
      data presented here show that the number of missing teeth does not have a
      significant influence on the frequency of occurrence of parafunctions.
      Parafunctions have become a very important factor in the diagnosis of diseases
      and pathological symptoms of eye and ear as the rate at which they occur is
      growing. CONCLUSIONS: The kind of parafunction is very important. Only those
      involving tooth contact should be taken into consideration when diagnosing eye
      and ear syndromes.

PMID- 22457684
TI  - Lunar phase does not influence perioperative complications in total hip
      arthroplasty.
AB  - INTRODUCTION: Lunar calendars, publishing recommendations for daily life, are
      gaining more and more attention in Germany, where 10.5% of the population believe
      in lunar effects on disease. A widespread and often heard belief is that a full
      moon has the most negative effects on surgical outcome. The present study
      evaluates the effects of lunar phase on perioperative complications in total hip
      arthroplasty. MATERIAL AND METHODS: We performed a retrospective study with 305
      patients being provided with a primary hip arthroplasty. To identify possible
      influences of the lunar phase on perioperative complications we investigated data
      such as operation length, blood loss and course of C-reactive protein that were
      collected during the patients' stay in the hospital and allocated them to moon
      illumination. RESULTS: There were no significant differences in all collected
      data concerning the lunar phase (p > 0.05). Although not statistically
      significant, there were fewer operations during the full moon phase. CONCLUSIONS:
      Therefore there is no evidence that lunar phase has an effect on perioperative
      complications in total hip arthroplasty. Fewer, though not significantly fewer,
      operations were performed during the full moon phase. Although this was not a
      prospective randomized trial, the statistical magnitude of the results does not
      support any recommendations for scheduling patients for total hip arthroplasty at
      any particular day of the lunar phase.

PMID- 22457685
TI  - Is pre-fracture functional status better than cognitive level in predicting short
      term outcome of elderly hip fracture patients?
AB  - INTRODUCTION: The aim of the study was to determine to what extent severe
      cognitive impairment impacts short-term rehabilitation outcomes of elderly
      patients with proximal hip fracture. MATERIAL AND METHODS: A total of 337
      community-dwelling elderly patients with acute hip fracture were observed during
      a 12-month period at a major teaching hospital in Serbia. Cognitive status was
      assessed at admission with the Short Portable Mental Status Questionnaire
      (SPMSQ). Outcome after 4 months was analysed with respect to presence of severe
      cognitive impairment, defined as an SPMSQ score of < 3. Outcome assessment
      included presence of postoperative complications, absolute motor Functional
      Independence Measure (FIM) gain, Activities of Daily Living index (ADL),
      Instrumental Activities of Daily Living score (IADL), and walking ability.
      RESULTS: An SPMSQ score of < 3 was observed in 36 patients (10.7%) with acute hip
      fracture. Patients with an SPMSQ score of < 3 achieved worse short-term outcomes
      regarding all observed variables. However, cognitive status was found to be an
      independent predictor only with respect to mortality at 4 months (odds ratio (OR)
      = 0.969, 95% confidence interval (CI) = 0.947-0.992, p = 0.009). In contrast, pre
      fracture motor FIM independently predicted mortality (OR = 2.982, 95% CI = 1.271
      7.000, p = 0.012), and preserved walking ability at 4 months follow-up (OR =
      0.945, 95% CI = 0.912-0.980, p = 0.002). Correspondingly, pre-fracture ADL was an
      independent predictor of absolute motor FIM gain at 4 months follow-up (OR =
      0.175, 95% CI = 0.405-11.426, p = 0.035). CONCLUSIONS: Failure to consider
      functional status prior to fracture might overestimate the impact of cognitive
      status on functional outcome of hip fracture patients.

PMID- 22457686
TI  - Irritable bowel syndrome treatment: cognitive behavioral therapy versus medical
      treatment.
AB  - INTRODUCTION: The study aims to investigate two kinds of treatment in patients
      suffering from irritable bowel syndrome (IBS) and consequently compares its
      efficacy on improving the symptoms and mental health of patients; one with just
      medical treatment and another through a combination of psychotherapy and medical
      treatment. MATERIAL AND METHODS: Applying general sampling, 50 IBS patients were
      selected from among those who used to refer to a Gastroenterology Clinic. After
      physical and mental evaluations based on ROME-II scale and SCL-90-R
      questionnaires, the subjects were randomly superseded into: the control group
      with medical treatment and, the case group with a combination of medical and
      psychological treatments. The acquired data were then analyzed through t-test and
      Mann-Whitney U-test. RESULTS: The findings show that the mental health of
      patients receiving cognitive behavioral therapy along with the medical treatment
      was higher than those of the control group at post-test level. It was observed
      that the therapy reduces the disability caused by IBS. Comparatively, while the
      cognitive therapy and medical treatments cured 80% of the patients, those
      receiving cognitive therapy alone showed an extensive reduction of symptoms.
      CONCLUSIONS: Considering the role of cognitive behavioral therapy, it is
      therefore recommend that such patients be managed by a combined team of
      gastroenterologists and psychologists.

PMID- 22457687
TI  - Application of Choynowski's Memory Scale in assessment of patients with dementia.
AB  - INTRODUCTION: Neuropsychological assessment of patients with dementia
      necessitates the use of varied memory tasks designed to measure different memory
      processes, including information memorization, retention and retrieval. A valid
      memory battery should be demonstrated to discriminate between demented and non
      demented subjects and its scores should be related to the degree of intellectual
      impairment. The objective of this study was to evaluate the potential usefulness
      of Choynowski's Memory Scale in assessment of patients with dementia. MATERIAL
      AND METHODS: Thirty-two patients with dementia and 64 age- and gender- matched
      healthy controls took part in the study. All participants were examined by means
      of Choynowski's Memory Scale, and the patients were additionally assessed by the
      Mini Mental State Examination and Clock Drawing Test (CDT). RESULTS: All subtests
      of Choynowski's Memory Scale were found to highly significantly (p <= 0.001)
      discriminate between patients with dementia and healthy controls. Except for
      Digit Span, all other subtests of Choynowski's battery were highly correlated
      with the global mental status as assessed by MMSE with correlation coefficients
      ranging from 0.59 to 0.81. Most subtests of Choynowski's Memory Scale were also
      moderately or highly correlated with performance on the CDT, and the correlations
      coefficients between the total score on Memory Scale and the CDT were r = 0.66
      and r = 0.61 (p <= 0.001) for the free recall drawing and copying, respectively.
      CONCLUSIONS: Choynowski's Memory Scale showed high discriminative properties and
      strong associations with the degree of intellectual impairment in dementia. The
      results encourage the use of this battery in clinical settings.

PMID- 22457691
TI  - Bovine arch.

PMID- 22457689
TI  - T lymphocytes as a target of histamine action.
AB  - Histamine is one of the most important biogenic amines in medicine and biology
      but its role in allergy, autoimmune and neoplastic diseases has not yet been
      fully defined. The last few years have brought many discoveries concerning
      important modulatory effects of histamine and its receptors on basic mechanisms
      of the immunological processes. The role of histamine H1 and H2 receptors in
      immunomodulation has been established. The immunomodulatory function of a newly
      described histamine H4 receptor has been revealed. One of the most important
      modulatory effects of histamine currently studied is its influence on T
      lymphocyte differentiation and function. Our present knowledge suggests that
      histamine may have a wider influence on various immunological processes than is
      now accepted; therefore, we need further studies to fully clarify the role of
      histamine and its receptors. This knowledge can bring new therapeutic solutions
      in allergies, autoimmune diseases and malignancies.

PMID- 22457690
TI  - Non-invasive detection of concomitant coronary artery anomaly and atherosclerotic
      coronary disease using transthoracic Doppler echocardiography.

PMID- 22457688
TI  - Relationship between paraoxonase and homocysteine: crossroads of oxidative
      diseases.
AB  - Homocysteine (Hcy) is an accepted independent risk factor for several major
      pathologies including cardiovascular disease, birth defects, osteoporosis,
      Alzheimer's disease, and renal failure. Interestingly, many of the pathologies
      associated with homocysteine are also linked to oxidative stress. The enzyme
      paraoxonase (PON1) - so named because of its ability to hydrolyse the toxic
      metabolite of parathion, paraoxon - was also shown early after its identification
      to manifest arylesterase activity. Although the preferred endogenous substrate of
      PON1 remains unknown, lactones comprise one possible candidate class.
      Homocysteine-thiolactone can be disposed of by enzymatic hydrolysis by the serum
      Hcy-thiolactonase/paraoxonase carried on high-density lipoprotein (HDL). In this
      review, Hcy and the PON1 enzyme family were scrutinized from different points of
      view in the literature and the recent articles on these subjects were examined to
      determine whether these two molecular groups are related to each other like a
      coin with two different sides, so close and yet so different and so opposite.

PMID- 22457692
TI  - Hypertension without renovascular stenosis: a rare case of abdominal aorta
      coarctation treated with percutaneous transluminal angioplasty.

PMID- 22457693
TI  - Isolated metastasis to the foot as an extremely rare presenting feature of
      primary endometrial cancer.

PMID- 22457694
TI  - Carney's complex: a successful pregnancy after bilateral adrenalectomy.

PMID- 22457695
TI  - Na, K-ATPase: Ubiquitous Multifunctional Transmembrane Protein and its Relevance
      to Various Pathophysiological Conditions.
AB  - The Na(+), K(+)-ATPase (NKA) is an ubiquitous enzyme consisting of alpha, beta
      and gamma subunits, and is responsible for the creation and maintenance of the
      Na(+) and K(+) gradients across the cell membrane by transporting 3 Na(+) out and
      2 K(+) into the cell. Sodium pump regulation is tissue as well as isoform
      specific. Intracellular messengers differentially regulate the activity of the
      individual NKA isozymes. Regulation of specific NKA isozymes gives cells the
      ability to precisely coordinate NKA activity to their physiological requirements.
      It is the only known receptor for the cardiac glycosides used to treat congestive
      heart failure and cardiac arrhythmias. Endogenous ligands structurally similar to
      cardiac glycosides may act as natural regulators of the sodium pump in heart and
      other tissues. Identification of naturally occurring regulators of  NKA could
      initiate the discovery of new hormone-like control systems involved in the
      etiology of selected disease processes, hence the importance of understanding the
      relation of the sodium pump and its ligands to disease. Diabetes has a marked
      effect on the metabolism of a variety of tissues and because the NKA is critical
      for the membrane potential and many transports, a change in its activity in
      diabetes would have profound consequence in these tissues. NKA is also involved
      in hypertension, salt balance, cardiovascular and renal disorders, sperm
      capacitation, cell volume regulation, apoptosis, rheumatoid arthritis, sepsis,
      neurological disorders, lung edema clearance and preeclampsia. NKA activity and
      expression in the collecting duct of kidney are modulated physiologically by
      hormones like aldosterone, vasopressin, and insulin. NKA enzyme activity and
      subunit levels are reduced in carcinoma, NKA-beta levels were highly reduced in
      an invasive form of human renal clear cell carcinoma, androgen-dependent prostate
      cancer, in early stages of urothelial cancer, as well as in poorly
      differentiated, highly motile carcinoma cell lines obtained from various tissues
      suggesting a functional link between reduced NKA-beta expression and cancer
      progression. It could be a target for the development of anticancer drugs as it
      serves as a signal transducer, it is a player in cell adhesion and its aberrant
      expression and activity are implicated in the development and progression of
      different cancers. KEYWORDS: Na(+), K(+)-ATPase (NKA); Cardiotonic steroids
      (CTS); Diabetes; Hypertension; Cardiovascular and renal disorders; Signal
      transducer; Anticancer drugs.

PMID- 22457696
TI  - Recurrent pregnancy loss and thrombophilia.
AB  - Emerging data seem to be available also on the role of active thromboprophylaxis
      with heparin and pregnancy outcome. In the last decades we found many data
      concerning the association between a hypercoagulable state and its causes and
      adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). First
      studies which focused on the association between thrombophilia and RPL underlined
      the role of reduced clotting inhibitors and RPL, and subsequent studies
      underlined a pathogenetic role of gene variant associated to hypercoagulable
      state in the occurrence of RPL. On the other hand, acquired thrombophilic
      abnormalities as antiphipsholipid syndrome are a well known cause of RPL and
      should be considered for a screening. These data are relevant because recent
      studies suggested a role of an extensive thromprophilaxis in women with RPL that
      should be addressed only in case of known thrombophilia and high risk of venous
      thromboembolism. KEYWORDS: Thrombophilia; Recurrent pregnancy loss; Factor V
      Leiden; Hyperhomocysteinemia; Antiphospholipid antibodies; PAI 4G?4G.

PMID- 22457697
TI  - Social Change Communication: Need of the Hour for the Prevention of HIV/AIDS.
AB  - For the last three decades or so, we all have been living with the pandemic of
      HIV and AIDS. Human behaviour is complex; widespread behaviour changes are
      challenging to achieve. Understanding the dynamics of HIV transmission can not be
      separated from an understanding of the broader context of poverty, inequality and
      social exclusion which create conditions where unsafe behaviour flourishes.
      HIV/AIDS is not a mere health issue: its occurrence is influenced by a number of
      socio-economic, cultural and ecological determinants. Social change communication
      is an inclusive way of responding to HIV/AIDS issues. Social change communication
      can tackle structural drivers of the HIV epidemic, with a particular focus on the
      drivers of gender inequality, stigma and discrimination, and human rights
      violations. Social change communication is bound to emerge as the vaccine and
      panacea for HIV and AIDS. KEYWORDS: HIV; AIDS; Behaviour; Social change
      communication.

PMID- 22457698
TI  - The Value of Patient-administered Depression Rating Scale in Detecting Cognitive
      Deficits in Depressed Patients.
AB  - BACKGROUND: The aims of this study was to clarify how accurate the depressed
      patients perceive their cognitive symptoms, and verify the appropriateness of the
      depressive rating scales in evaluating cognitive deficits in major depressive
      disorder (MDD) patients. METHODS: The subjects consisted of 19 well-characterized
      medication-free patients with MDD and 19 healthy volunteers. The clinical and
      neuropsychological assessments, including Hamilton Rating Scale for Depression
      (HAM-D), Taiwanese Depression Questionnaire (TDQ), Finger Tapping Test, Wechsler
      Memory Scale-Revised, Stroop Color-Word Test, and Continuous Performance Test,
      were administered at the time of recruitment and repeated six months after
      treatment. RESULTS: Depressed patients exhibited significant impairment in
      several neurocognitive domains. Neurocognitive impairment was correlated with
      both the affective and somatic factors, but not with the cognitive factors of
      TDQ. The similar results were shown after 6-month treatment. CONCLUSIONS: Our
      results suggest that the MDD patients do not perceive their cognitive dysfunction
      correctly. The depression rating scales, especially the patient-administered
      scale, need to be validated for measuring neurocognitive deficits of MDD patients
      in the future, if cognitive component is suspected as one of the major domains of
      self-rating scale. KEYWORDS: Major depressive disorder; Cognitive deficits;
      Depression rating scale.

PMID- 22457699
TI  - Prevalence and Immunization Status of Hepatitis B Virus in the HIV Cohort in
      Fife, Scotland.
AB  - BACKGROUND: Routes of transmission of hepatitis B virus (HBV)/HIV infections are
      similar and there is a significant rate of co-infection in patients. A study was
      recently carried out in NHS Fife, Scotland from February 2007 - February 2008 to
      estimate the prevalence of HBV/HIV co-infection, occult HBV infection and
      immunisation status against HBV in a cohort of patients with HIV attending the
      departments of infectious diseases and genitourinary medicine. METHODS: Case
      notes were reviewed retrospectively (n = 70). Details on patient demographics,
      risk category, nadir/current CD4 count, HIV viral load and vaccination history
      were analysed. HBV markers (HBsAg/anti-HBs/anti-HBc/HBV DNA) and alanine
      transaminase (ALT) levels were tested prospectively if these tests had not been
      carried out in the previous 12 months. RESULTS AND CONCLUSION: Prevalence of
      HBV/HIV co-infection was 5.6% of which 2.8% of patients had occult infection and
      22.9% had evidence of previous exposure. Although HBV is preventable by
      vaccination, only 24.2% of patients had been vaccinated against it. Improvements
      could therefore be made in the field of prevention with vaccination and
      monitoring the immune response in this cohort. KEYWORDS: Prevalence; Immunization
      status; Hepatitis B Virus; HIV.

PMID- 22457700
TI  - Depression and recovery of daily life autonomy in patients with stroke receiving
      home rehabilitative treatment.
AB  - BACKGROUND: The object of this study was to evaluate the prevalence of post
      stroke depression and its possible role as a predictive negative factor in
      patients receiving home rehabilitation treatment. METHODS: We analyzed 103
      patients with stroke by correlating comorbidities, clinical and blood test
      parameters and characteristics of the lesion with depression class identified
      according to the Hamilton scale and the outcome of the rehabilitation program.
      RESULTS: A significant association between hypertension and post-stroke severe
      depression emerged in the female patients. CONCLUSIONS: Since the literature
      offers conflicting data, our results may contribute a stimulus for further
      studies. KEYWORDS: Home care; Rehabilitation; Stroke; Depression; Hypertension.

PMID- 22457701
TI  - Cyclic vomiting syndrome in a male patient with history of renal cell carcinoma
      status post nephrectomy.
AB  - Cyclic vomiting syndrome (CVS) is a condition whose symptoms are recurring
      attacks of intense nausea, vomiting and sometimes abdominal pain and/or headaches
      or migraines. Cyclic vomiting usually develops during the childhood ages of 3 -
      7; whereas it often remits during adolescence, it can persist into adult life. We
      report a case of a 57 years old Caucasian male with a history of renal cell
      carcinoma status post left nephrectomy presenting with a 7 years history of
      intermittent nausea and vomiting with prodromal malaise, watery diarrhea,
      flushing and diaphoresis. Cyclic vomiting syndrome is a debilitating functional
      brain-gut disorder that was initially characterized in children, but now is
      increasingly recognized to occur also in adults. KEYWORDS: Cyclic vomiting
      syndrome; Vomitting; Post nephrectomy.

PMID- 22457702
TI  - A Primary Testicular Diffuse Large B-cell Lymphoma Belonging to the Germinal
      Center B-cell-like Group.
AB  - Testicular lymphoma was first reported by Malassez and Curling in 1866. Primary
      testicular lymphoma constitutes only 1 - 7% of all testicular neoplasms and less
      than 1% of all non Hodgkin lymphoma. The authors report a new case of primary
      testicular lymphoma and highlight its diagnostic and therapeutic challenge. We
      report the case of a 26-year old man without a particular past medical history,
      who presented with a painful right testicular swelling that he has noticed for
      several weeks. Radiological findings consisted in multiple hypoechoic masses that
      corresponded in histological examination to a diffuse intratubular lymphomatous
      infiltration situated away from the spermatic cord, the epididymis, ductuli
      efferentes and rete testis. Immunohistochemical study showed positivity for
      leukocytic common antigen (CD45), B-cell marker (CD20) and bcl 6. The patient
      underwent full staging for lymphoma showing no evidence of extra-testicular
      involvement by lymphoma and no lymph nodes. The diagnosis of stage I primary
      testicular large B-cell lymphoma of germinal center B-cell-like group was made.
      The patient is now treated by chemotherapy. Primary testicular lymphoma is a rare
      tumour whose diagnosis is based on histological findings. There are non
      consensual etiological or predisposing factors. Treatment modalities consist in
      surgical excision, chemotherapy and radiation therapy but the accurate procedures
      are not standardized. Factors that have been linked to more favorable outcomes
      include younger patient age, localized disease, presence of sclerosis at
      pathologic analysis, smaller tumour size, lower histological tumor grade and lack
      of epididymal or spermatic cord involvement. KEYWORDS: Testicular lymphoma;
      Germinal center; B-cell.

PMID- 22457703
TI  - Successful cardiopulmonary resuscitation in pregnancy: a case report.
AB  - The management of cardiac arrest in pregnancy is an important task for the
      emergency physicians. The clinical outcome of mother or fetus will often depend
      on the successful resuscitation of the first few minutes. Furthermore, the
      resuscitation team leader should consider the necessity of emergency hysterotomy
      (cesarean delivery) as soon as a pregnant woman develops cardiac arrest. We
      report a case of a 28-year-old pregnant woman who had a ventricular fibrillation
      cardiac arrest. She was successfully resuscitated in our emergency department and
      a single male healthy infant was delivered via cesarean section at 36 weeks'
      gestation. Mother and baby were discharged survival and neurologically intact
      from the intensive care unit (ICU) on day 25. We emphasize that understanding the
      causes of cardiac arrest during pregnancy, its early recognition and prompt
      resuscitation by recent ACLS guidelines may decrease both maternal and fetal
      morbidity or mortality. KEYWORDS: Cardiac arrest; Cardiopulmonary resuscitation;
      Cesarean delivery; Fetus; Pregnant.

PMID- 22457704
TI  - B-cell lymphoma of the thoracic spine presenting with spinal cord pressure
      syndrome.

PMID- 22457705
TI  - An automated method to quantify microglia morphology and application to monitor
      activation state longitudinally in vivo.
AB  - Microglia are specialized immune cells of the brain. Upon insult, microglia
      initiate a cascade of cellular responses including a characteristic change in
      cell morphology. To study the dynamics of microglia immune response in situ, we
      developed an automated image analysis method that enables the quantitative
      assessment of microglia activation state within tissue based solely on cell
      morphology. Per cell morphometric analysis of fluorescently labeled microglia is
      achieved through local iterative threshold segmentation, which reduces errors
      caused by signal-to-noise variation across large volumes. We demonstrate,
      utilizing systemic application of lipopolysaccharide as a model of immune
      challenge, that several morphological parameters, including cell perimeter
      length, cell roundness and soma size, quantitatively distinguish resting versus
      activated populations of microglia within tissue comparable to traditional
      immunohistochemistry methods. Furthermore, we provide proof-of-concept data that
      monitoring soma size enables the longitudinal assessment of microglia activation
      in the mouse neocortex imaged via 2-photon in vivo microscopy. The ability to
      quantify microglia activation automatically by shape alone allows unbiased and
      rapid analysis of both fixed and in vivo central nervous system tissue.

PMID- 22457708
TI  - Liver x receptors regulate the transcriptional activity of the glucocorticoid
      receptor: implications for the carbohydrate metabolism.
AB  - GLUCOCORTICOIDS are steroid hormones that strongly influence intermediary
      carbohydrate metabolism by increasing the transcription rate of glucose-6
      phosphatase (G6Pase), a key enzyme of gluconeogenesis, and suppress the immune
      system through the glucocorticoid receptor (GR). The liver X receptors (LXRs), on
      the other hand, bind to cholesterol metabolites, heterodimerize with the retinoid
      X receptor (RXR), and regulate the cholesterol turnover, the hepatic glucose
      metabolism by decreasing the expression of G6Pase, and repress a set of
      inflammatory genes in immune cells. Since the actions of these receptors overlap
      with each other, we evaluated the crosstalk between the GR- and LXR-mediated
      signaling systems. Transient transfection-based reporter assays and gene
      silencing methods using siRNAs for LXRs showed that overexpression/ligand
      (GW3965) activation of LXRs/RXRs repressed GR-stimulated transactivation of
      certain glucocorticoid response element (GRE)-driven promoters in a gene-specific
      fashion. Activation of LXRs by GW3965 attenuated dexamethasone-stimulated
      elevation of circulating glucose in rats. It also suppressed dexamethasone
      induced mRNA expression of hepatic glucose-6-phosphatase (G6Pase) in rats, mice
      and human hepatoma HepG2 cells, whereas endogenous, unliganded LXRs were required
      for dexamethasone-induced mRNA expression of phosphoenolpyruvate carboxylase. In
      microarray transcriptomic analysis of rat liver, GW3965 differentially regulated
      glucocorticoid-induced transcriptional activity of about 15% of endogenous
      glucocorticoid-responsive genes. To examine the mechanism through which activated
      LXRs attenuated GR transcriptional activity, we examined LXRalpha/RXRalpha
      binding to GREs. Endogenous LXRalpha/RXRalpha bound GREs and inhibited GR binding
      to these DNA sequences both in in vitro and in vivo chromatin immunoprecipitation
      assays, while their recombinant proteins did so on classic or G6Pase GREs in gel
      mobility shift assays. We propose that administration of LXR agonists may be
      beneficial in glucocorticoid treatment- or stress-associated dysmetabolic states
      by directly and gene-specifically attenuating the transcriptional activity of the
      GR on glucose and/or lipid metabolism.

PMID- 22457709
TI  - Mitochondrial DNA variation, but not nuclear DNA, sharply divides morphologically
      identical chameleons along an ancient geographic barrier.
AB  - The Levant is an important migration bridge, harboring border-zones between
      Afrotropical and palearctic species. Accordingly, Chameleo chameleon, a common
      species throughout the Mediterranean basin, is morphologically divided in the
      southern Levant (Israel) into two subspecies, Chamaeleo chamaeleon recticrista
      (CCR) and C. c. musae (CCM). CCR mostly inhabits the Mediterranean climate
      (northern Israel), while CCM inhabits the sands of the north-western Negev Desert
      (southern Israel). AFLP analysis of 94 geographically well dispersed specimens
      indicated moderate genetic differentiation (PhiPT = 0.097), consistent with the
      classical division into the two subspecies, CCR and CCM. In contrast, sequence
      analysis of a 637 bp coding mitochondrial DNA (mtDNA) fragment revealed two
      distinct phylogenetic clusters which were not consistent with the morphological
      division: one mtDNA cluster consisted of CCR specimens collected in regions
      northern of the Jezreel Valley and another mtDNA cluster harboring specimens
      pertaining to both the CCR and CCM subspecies but collected southern of the
      Jezreel Valley. AMOVA indicated clear mtDNA differentiation between specimens
      collected northern and southern to the Jezreel Valley (PhiPT = 0.79), which was
      further supported by a very low coalescent-based estimate of effective migration
      rates. Whole chameleon mtDNA sequencing (~17,400 bp) generated from 11 well
      dispersed geographic locations revealed 325 mutations sharply differentiating the
      two mtDNA clusters, suggesting a long allopatric history further supported by
      BEAST. This separation correlated temporally with the existence of an at least 1
      million year old marine barrier at the Jezreel Valley exactly where the mtDNA
      clusters meet. We discuss possible involvement of gender-dependent life history
      differences in maintaining such mtDNA genetic differentiation and suggest that it
      reflects (ancient) local adaptation to mitochondrial-related traits.

PMID- 22457711
TI  - Eimeripain, a cathepsin B-like cysteine protease, expressed throughout
      sporulation of the apicomplexan parasite Eimeria tenella.
AB  - The invasion and replication of Eimeria tenella in the chicken intestine is
      responsible for avian coccidiosis, a disease that has major economic impacts on
      poultry industries worldwide. E. tenella is transmitted to naive animals via shed
      unsporulated oocysts that need contact with air and humidity to form the
      infectious sporulated oocysts, which contain the first invasive form of the
      parasite, the sporozoite. Cysteine proteases (CPs) are major virulence factors
      expressed by protozoa. In this study, we show that E. tenella expresses five
      transcriptionally regulated genes encoding one cathepsin L, one cathepsin B and
      three cathepsin Cs. Biot-LC-LVG-CHN2, a cystatin derived probe, tagged eight
      polypeptides in unsporulated oocysts but only one in sporulated oocysts. CP
      dependant activities were found against the fluorescent substrates, Z-FR-AMC and
      Z-LR-AMC, throughout the sporulation process. These activities corresponded to a
      cathepsin B-like enzyme since they were inhibited by CA-074, a specific cathepsin
      B inhibitor. A 3D model of the catalytic domain of the cathepsin B-like protease,
      based on its sequence homology with human cathepsin B, further confirmed its
      classification as a papain-like protease with similar characteristics to toxopain
      1 from the related apicomplexan parasite, Toxoplasma gondii; we have, therefore,
      named the E. tenella cathepsin B, eimeripain. Following stable transfection of E.
      tenella sporozoites with a plasmid allowing the expression of eimeripain fused to
      the fluorescent protein mCherry, we demonstrated that eimeripain is detected
      throughout sporulation and has a punctate distribution in the bodies of extra-
      and intracellular parasites. Furthermore, CA-074 Me, the membrane-permeable
      derivative of CA-074, impairs invasion of epithelial MDBK cells by E. tenella
      sporozoites. This study represents the first characterization of CPs expressed by
      a parasite from the Eimeria genus. Moreover, it emphasizes the role of CPs in
      transmission and dissemination of exogenous stages of apicomplexan parasites.

PMID- 22457710
TI  - Incidence of schizophrenia and other psychoses in England, 1950-2009: a
      systematic review and meta-analyses.
AB  - BACKGROUND: We conducted a systematic review of incidence rates in England over a
      sixty-year period to determine the extent to which rates varied along accepted
      (age, sex) and less-accepted epidemiological gradients (ethnicity, migration and
      place of birth and upbringing, time). OBJECTIVES: To determine variation in
      incidence of several psychotic disorders as above. DATA SOURCES: Published and
      grey literature searches (MEDLINE, PSycINFO, EMBASE, CINAHL, ASSIA, HMIC), and
      identification of unpublished data through bibliographic searches and author
      communication. STUDY ELIGIBILITY CRITERIA: Published 1950-2009; conducted wholly
      or partially in England; original data on incidence of non-organic adult-onset
      psychosis or one or more factor(s) pertaining to incidence. PARTICIPANTS: People,
      16-64 years, with first -onset psychosis, including non-affective psychoses,
      schizophrenia, bipolar disorder, psychotic depression and substance-induced
      psychosis. STUDY APPRAISAL AND SYNTHESIS METHODS: Title, abstract and full-text
      review by two independent raters to identify suitable citations. Data were
      extracted to a standardized extraction form. Descriptive appraisals of variation
      in rates, including tables and forest plots, and where suitable, random-effects
      meta-analyses and meta-regressions to test specific hypotheses; rate
      heterogeneity was assessed by the I2-statistic. RESULTS: 83 citations met
      inclusion. Pooled incidence of all psychoses (N = 9) was 31.7 per 100,000 person
      years (95%CI: 24.6-40.9), 23.2 (95%CI: 18.3-29.5) for non-affective psychoses (N
      = 8), 15.2 (95%CI: 11.9-19.5) for schizophrenia (N = 15) and 12.4 (95%CI: 9.0
      17.1) for affective psychoses (N = 7). This masked rate heterogeneity (I2: 0.54
      0.97), possibly explained by socio-environmental factors; our review confirmed
      (via meta-regression) the typical age-sex interaction in psychosis risk,
      including secondary peak onset in women after 45 years. Rates of most disorders
      were elevated in several ethnic minority groups compared with the white (British)
      population. For example, for schizophrenia: black Caribbean (pooled RR: 5.6;
      95%CI: 3.4-9.2; N = 5), black African (pooled RR: 4.7; 95%CI: 3.3-6.8; N = 5) and
      South Asian groups in England (pooled RR: 2.4; 95%CI: 1.3-4.5; N = 3). We found
      no evidence to support an overall change in the incidence of psychotic disorder
      over time, though diagnostic shifts (away from schizophrenia) were reported.
      LIMITATIONS: Incidence studies were predominantly cross-sectional, limiting
      causal inference. Heterogeneity, while evidencing important variation, suggested
      pooled estimates require interpretation alongside our descriptive systematic
      results. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Incidence of psychotic
      disorders varied markedly by age, sex, place and migration status/ethnicity.
      Stable incidence over time, together with a robust socio-environmental
      epidemiology, provides a platform for developing prediction models for health
      service planning.

PMID- 22457712
TI  - A genome-wide association study identifies two novel promising candidate genes
      affecting Escherichia coli F4ab/F4ac susceptibility in swine.
AB  - Enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbria is the major
      pathogenic bacteria causing diarrhoea in neonatal and post-weaning piglets.
      Previous studies have revealed that the susceptibility to ETEC F4ab/F4ac is an
      autosomal Mendelian dominant trait and the loci controlling the F4ab/F4ac
      receptor are located on SSC13q41, between markers SW207 and S0283. To pinpoint
      these loci and further validate previous findings, we performed a genome-wide
      association study (GWAS) using a two generation family-based population,
      consisting of 301 piglets with phenotypes of susceptibility to ETEC F4ab/F4ac by
      the vitro adhesion test. The DNA of all piglets and their parents was genotyped
      using the Illumina PorcineSNP60 BeadChip, and 50,972 and 50,483 SNPs were
      available for F4ab and F4ac susceptibility, respectively, in the association
      analysis after quality control. In summary, 28 and 18 significant SNPs (p<0.05)
      were detected associated with F4ab and F4ac susceptibility respectively at genome
      wide significance level. From these significant findings, two novel candidate
      genes, HEG1 and ITGB5, were firstly identified as the most promising genes
      underlying F4ab/F4ac susceptibility in swine according to their functions and
      positions. Our findings herein provide a novel evidence for unravelling genetic
      mechanism of diarrhoea risk in piglets.

PMID- 22457713
TI  - Impaired trunk stability in individuals at high risk for Parkinson's disease.
AB  - BACKGROUND: The search for disease-modifying treatments for Parkinson's disease
      advances, however necessary markers for early detection of the disease are still
      lacking. There is compelling evidence that changes of postural stability occur at
      very early clinical stages of Parkinson's disease, making it tempting to
      speculate that changes in sway performance may even occur at a prodromal stage,
      and may have the potential to serve as a prodromal marker for the disease.
      METHODOLOGY/PRINCIPAL FINDINGS: Balance performance was tested in 20 individuals
      with an increased risk of Parkinson's disease, 12 Parkinson's disease patients
      and 14 controls using a cross-sectional approach. All individuals were 50 years
      or older. Investigated groups were similar with respect to age, gender, and
      height. An accelerometer at the centre of mass at the lower spine quantified sway
      during quiet semitandem stance with eyes open and closed, as well as with and
      without foam. With increasing task difficulty, individuals with an increased risk
      of Parkinson's disease showed an increased variability of trunk acceleration and
      a decrease of smoothness of sway, compared to both other groups. These
      differences reached significance in the most challenging condition, i.e. the eyes
      closed with foam condition. CONCLUSIONS/SIGNIFICANCE: Individuals with an
      increased risk of Parkinson's disease have subtle signs of a balance deficit
      under most challenging conditions. This preliminary finding should motivate
      further studies on sway performance in individuals with an increased risk of
      Parkinson's disease, to evaluate the potential of this symptom to serve as a
      biological marker for prodromal Parkinson's disease.

PMID- 22457714
TI  - Sample size under inverse negative binomial group testing for accuracy in
      parameter estimation.
AB  - BACKGROUND: The group testing method has been proposed for the detection and
      estimation of genetically modified plants (adventitious presence of unwanted
      transgenic plants, AP). For binary response variables (presence or absence),
      group testing is efficient when the prevalence is low, so that estimation,
      detection, and sample size methods have been developed under the binomial model.
      However, when the event is rare (low prevalence <0.1), and testing occurs
      sequentially, inverse (negative) binomial pooled sampling may be preferred.
      METHODOLOGY/PRINCIPAL FINDINGS: This research proposes three sample size
      procedures (two computational and one analytic) for estimating prevalence using
      group testing under inverse (negative) binomial sampling. These methods provide
      the required number of positive pools ([Formula: see text]), given a pool size
      (k), for estimating the proportion of AP plants using the Dorfman model and
      inverse (negative) binomial sampling. We give real and simulated examples to show
      how to apply these methods and the proposed sample-size formula. The Monte Carlo
      method was used to study the coverage and level of assurance achieved by the
      proposed sample sizes. An R program to create other scenarios is given in
      Appendix S2. CONCLUSIONS: The three methods ensure precision in the estimated
      proportion of AP because they guarantee that the width (W) of the confidence
      interval (CI) will be equal to, or narrower than, the desired width ([Formula:
      see text]), with a probability of [Formula: see text]. With the Monte Carlo study
      we found that the computational Wald procedure (method 2) produces the more
      precise sample size (with coverage and assurance levels very close to nominal
      values) and that the samples size based on the Clopper-Pearson CI (method 1) is
      conservative (overestimates the sample size); the analytic Wald sample size
      method we developed (method 3) sometimes underestimated the optimum number of
      pools.

PMID- 22457715
TI  - Origin of the diversity in DNA recognition domains in phasevarion associated modA
      genes of pathogenic Neisseria and Haemophilus influenzae.
AB  - Phase variable restriction-modification (R-M) systems have been identified in a
      range of pathogenic bacteria. In some it has been demonstrated that the random
      switching of the mod (DNA methyltransferase) gene mediates the coordinated
      expression of multiple genes and constitutes a phasevarion (phase variable
      regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable,
      DNA recognition domain (DRD) that defines the target sequence that is modified by
      methylation and is used to define modA alleles. 18 distinct modA alleles have
      been identified in H. influenzae and the pathogenic Neisseria. To determine the
      origin of DRD variability, the 18 modA DRDs were used to search the available
      databases for similar sequences. Significant matches were identified between
      several modA alleles and mod gene from distinct bacterial species, indicating one
      source of the DRD variability was via horizontal gene transfer. Comparison of DRD
      sequences revealed significant mosaicism, indicating exchange between the
      Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele
      similarity indicate that some modA alleles had undergone recombination more
      frequently than others, generating further diversity. Furthermore, the DRD from
      some modA alleles, such as modA12, have been transferred en bloc to replace the
      DRD from different modA alleles.

PMID- 22457716
TI  - Pulmonary function and incident bronchitis and asthma in children: a community
      based prospective cohort study.
AB  - BACKGROUND: Previous studies revealed that reduction of airway caliber in infancy
      might increase the risks for wheezing and asthma. However, the evidence for the
      predictive effects of pulmonary function on respiratory health in children was
      still inconsistent. METHODS: We conducted a population-based prospective cohort
      study among children in 14 Taiwanese communities. There were 3,160 children
      completed pulmonary function tests in 2007 and follow-up questionnaire in 2009.
      Poisson regression models were performed to estimate the effect of pulmonary
      function on the development of bronchitis and asthma. RESULTS: After adjustment
      for potential confounders, pulmonary function indices consistently showed
      protective effects on respiratory diseases in children. The incidence rate ratios
      of bronchitis and asthma were 0.86 (95% CI 0.79-0.95) and 0.91 (95% CI 0.82-0.99)
      for forced expiratory volume in 1 second (FEV1). Similar adverse effects of
      maximal mid-expiratory flow (MMEF) were also observed on bronchitis (RR = 0.73,
      95% CI 0.67-0.81) and asthma (RR = 0.85, 95% CI 0.77-0.93). We found significant
      decreasing trends in categorized FEV1 (p for trend = 0.02) and categories of MMEF
      (p for trend = 0.01) for incident bronchitis. Significant modification effects of
      traffic-related air pollution were noted for FEV1 and MMEF on bronchitis and also
      for MMEF on asthma. CONCLUSIONS: Children with high pulmonary function would have
      lower risks on the development of bronchitis and asthma. The protective effect of
      high pulmonary function would be modified by traffic-related air pollution
      exposure.

PMID- 22457717
TI  - Protecting important sites for biodiversity contributes to meeting global
      conservation targets.
AB  - Protected areas (PAs) are a cornerstone of conservation efforts and now cover
      nearly 13% of the world's land surface, with the world's governments committed to
      expand this to 17%. However, as biodiversity continues to decline, the
      effectiveness of PAs in reducing the extinction risk of species remains largely
      untested. We analyzed PA coverage and trends in species' extinction risk at
      globally significant sites for conserving birds (10,993 Important Bird Areas,
      IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero
      Extinction sites, AZEs) (referred to collectively hereafter as 'important
      sites'). Species occurring in important sites with greater PA coverage
      experienced smaller increases in extinction risk over recent decades: the
      increase was half as large for bird species with>50% of the IBAs at which they
      occur completely covered by PAs, and a third lower for birds, mammals and
      amphibians restricted to protected AZEs (compared with unprotected or partially
      protected sites). Globally, half of the important sites for biodiversity
      conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of
      important sites has increased over time, the proportion of PA area covering
      important sites, as opposed to less important land, has declined (by 0.45-1.14%
      annually since 1950 for IBAs and 0.79-1.49% annually for AZEs). Thus, while
      appropriately located PAs may slow the rate at which species are driven towards
      extinction, recent PA network expansion has under-represented important sites. We
      conclude that better targeted expansion of PA networks would help to improve
      biodiversity trends.

PMID- 22457718
TI  - Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast
      cancer cells.
AB  - Benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables,
      inhibits growth of breast cancer cells but the mechanisms underlying growth
      inhibitory effect of BITC are not fully understood. Here, we demonstrate that
      BITC treatment causes FoxO1-mediated autophagic death in cultured human breast
      cancer cells. The BITC-treated breast cancer cells (MDA-MB-231, MCF-7, MDA-MB
      468, BT-474, and BRI-JM04) and MDA-MB-231 xenografts from BITC-treated mice
      exhibited several features characteristic of autophagy, including appearance of
      double-membrane vacuoles (transmission electron microscopy) and acidic vesicular
      organelles (acridine orange staining), cleavage of microtubule-associated protein
      1 light chain 3 (LC3), and/or suppression of p62 (p62/SQSTM1 or sequestosome 1)
      expression. On the other hand, a normal human mammary epithelial cell line (MCF
      10A) was resistant to BITC-induced autophagy. BITC-mediated inhibition of MDA-MB
      231 and MCF-7 cell viability was partially but statistically significantly
      attenuated in the presence of autophagy inhibitors 3-methyl adenine and
      bafilomycin A1. Stable overexpression of Mn-superoxide dismutase, which was fully
      protective against apoptosis, conferred only partial protection against BITC
      induced autophagy. BITC treatment decreased phosphorylation of mTOR and its
      downstream targets (P70s6k and 4E-BP1) in cultured MDA-MB-231 and MCF-7 cells and
      MDA-MB-231 xenografts, but activation of mTOR by transient overexpression of its
      positive regulator Rheb failed to confer protection against BITC-induced
      autophagy. Autophagy induction by BITC was associated with increased expression
      and acetylation of FoxO1. Furthermore, autophagy induction and cell growth
      inhibition resulting from BITC exposure were significantly attenuated by small
      interfering RNA knockdown of FoxO1. In conclusion, the present study provides
      novel insights into the molecular circuitry of BITC-induced cell death involving
      FoxO1-mediated autophagy.

PMID- 22457719
TI  - Phenomenological analysis of ATP dependence of motor proteins.
AB  - In this study, through phenomenological comparison of the velocity-force data of
      processive motor proteins, including conventional kinesin, cytoplasmic dynein and
      myosin V, I found that, the ratio between motor velocities of two different ATP
      concentrations is almost invariant for any substall, superstall or negative
      external loads. Therefore, the velocity of motors can be well approximated by a
      Michaelis-Menten like formula V = [ATP]k(F)L([ATP] + K(M)), with L the step size,
      and k(F) the external load F dependent rate of one mechanochemical cycle of motor
      motion in saturated ATP solution. The difference of Michaelis-Menten constant
      K(M) for substall, superstall and negative external load indicates, the
      configurations at which ATP molecule can bind to motor heads for these three
      cases might be different, though the expression of k(F) as a function of F might
      be unchanged for any external load F. Verifications of this Michaelis-Menten like
      formula has also been done by fitting to the recent experimental data.

PMID- 22457720
TI  - Transient protein-protein interaction of the SH3-peptide complex via closely
      located multiple binding sites.
AB  - Protein-protein interactions play an essential role in cellular processes.
      Certain proteins form stable complexes with their partner proteins, whereas
      others function by forming transient complexes. The conventional protein-protein
      interaction model describes an interaction between two proteins under the
      assumption that a protein binds to its partner protein through a single binding
      site. In this study, we improved the conventional interaction model by developing
      a Multiple-Site (MS) model in which a protein binds to its partner protein
      through closely located multiple binding sites on a surface of the partner
      protein by transiently docking at each binding site with individual binding free
      energies. To test this model, we used the protein-protein interaction mediated by
      Src homology 3 (SH3) domains. SH3 domains recognize their partners via a weak,
      transient interaction and are therefore promiscuous in nature. Because the MS
      model requires large amounts of data compared with the conventional interaction
      model, we used experimental data from the positionally addressable syntheses of
      peptides on cellulose membranes (SPOT-synthesis) technique. From the analysis of
      the experimental data, individual binding free energies for each binding site of
      peptides were extracted. A comparison of the individual binding free energies
      from the analysis with those from atomistic force fields gave a correlation
      coefficient of 0.66. Furthermore, application of the MS model to 10 SH3 domains
      lowers the prediction error by up to 9% compared with the conventional
      interaction model. This improvement in prediction originates from a more
      realistic description of complex formation than the conventional interaction
      model. The results suggested that, in many cases, SH3 domains increased the
      protein complex population through multiple binding sites of their partner
      proteins. Our study indicates that the consideration of general complex formation
      is important for the accurate description of protein complex formation, and
      especially for those of weak or transient protein complexes.

PMID- 22457721
TI  - Genital HSV-2 infection induces short-term NK cell memory.
AB  - NK cells are known as innate immune cells that lack immunological memory.
      Recently, it has been shown that NK cells remember encounters with chemical
      haptens that induce contact hypersensitivity and cytomegalovirus infection. Here,
      we show the existence of NK cell memory following HSV-2 infection. Stimulation
      with HSV-2 Ags led to higher IFNgamma production in NK cells that were exposed 30
      days previously to HSV-2, compared to NK cells from naive mice. More importantly,
      this increased production of IFNgamma in NK cells was independent of B- and T-
      lymphocytes and specific for the HSV-2 Ags. We also showed that previously
      exposed NK cells in a B- and T-lymphocyte free environment mediate protection
      against HSV-2 infection and they are necessary for the protection of mice against
      HSV-2 infection. Collectively, NK cells remember prior HSV-2 encounters
      independent of B- and T- lymphocytes leading to protection against HSV-2 mediated
      morbidity and mortality upon re-exposure.

PMID- 22457722
TI  - Evidence for a trade-off strategy in stone oak (Lithocarpus) seeds between
      physical and chemical defense highlights fiber as an important antifeedant.
AB  - Trees in the beech or oak family (Fagaceae) have a mutualistic relationship with
      scatter-hoarding rodents. Rodents obtain nutrients and energy by consuming seeds,
      while providing seed dispersal for the tree by allowing some cached seeds to
      germinate. Seed predation and caching behavior of rodents is primarily affected
      by seed size, mechanical protection, macronutrient content, and chemical
      antifeedants. To enhance seed dispersal, trees must optimize trade-offs in
      investment between macronutrients and antifeedants. Here, we examine this
      important chemical balance in the seeds of tropical stone oak species with two
      substantially different fruit morphologies. These two distinct fruit morphologies
      in Lithocarpus differ in the degree of mechanical protection of the seed. For
      'acorn' fruit, a thin exocarp forms a shell around the seed while for 'enclosed
      receptacle' (ER) fruit, the seed is embedded in a woody receptacle. We compared
      the chemical composition of numerous macronutrient and antifeedant in seeds from
      several Lithocarpus species, focusing on two pairs of sympatric species with
      different fruit morphologies. We found that macronutrients, particularly total
      non-structural carbohydrate, was more concentrated in seeds of ER fruits while
      antifeedants, primarily fibers, were more concentrated in seeds of acorn fruits.
      The trade-off in these two major chemical components was more evident between the
      two sympatric lowland species than between two highland species. Surprisingly, no
      significant difference in overall tannin concentrations in the seeds was observed
      between the two fruit morphologies. Instead, the major trade-off between
      macronutrients and antifeedants involved indigestible fibers. Future studies of
      this complex mutualism should carefully consider the role of indigestible fibers
      in the foraging behavior of scatter-hoarding rodents.

PMID- 22457723
TI  - Biosafety of non-surface modified carbon nanocapsules as a potential alternative
      to carbon nanotubes for drug delivery purposes.
AB  - BACKGROUND: Carbon nanotubes (CNTs) have found wide success in circuitry,
      photovoltaics, and other applications. In contrast, several hurdles exist in
      using CNTs towards applications in drug delivery. Raw, non-modified CNTs are
      widely known for their toxicity. As such, many have attempted to reduce CNT
      toxicity for intravenous drug delivery purposes by post-process surface
      modification. Alternatively, a novel sphere-like carbon nanocapsule (CNC)
      developed by the arc-discharge method holds similar electric and thermal
      conductivities, as well as high strength. This study investigated the systemic
      toxicity and biocompatibility of different non-surface modified carbon
      nanomaterials in mice, including multi-walled carbon nanotubes (MWCNTs), single
      walled carbon nanotubes (SWCNTs), carbon nanocapsules (CNCs), and C 60 fullerene
      (C 60). The retention of the nanomaterials and systemic effects after intravenous
      injections were studied. METHODOLOGY AND PRINCIPAL FINDINGS: MWCNTs, SWCNTs,
      CNCs, and C 60 were injected intravenously into FVB mice and then sacrificed for
      tissue section examination. Inflammatory cytokine levels were evaluated with
      ELISA. Mice receiving injection of MWCNTs or SWCNTs at 50 ug/g b.w. died while C
      60 injected group survived at a 50% rate. Surprisingly, mortality rate of mice
      injected with CNCs was only at 10%. Tissue sections revealed that most carbon
      nanomaterials retained in the lung. Furthermore, serum and lung-tissue cytokine
      levels did not reveal any inflammatory response compared to those in mice
      receiving normal saline injection. CONCLUSION: Carbon nanocapsules are more
      biocompatible than other carbon nanomaterials and are more suitable for
      intravenous drug delivery. These results indicate potential biomedical use of non
      surface modified carbon allotrope. Additionally, functionalization of the carbon
      nanocapsules could further enhance dispersion and biocompatibility for
      intravenous injection.

PMID- 22457724
TI  - High density microarray analysis reveals new insights into genetic footprints of
      Listeria monocytogenes strains involved in listeriosis outbreaks.
AB  - Listeria monocytogenes, a foodborne bacterial pathogen, causes invasive and
      febrile gastroenteritis forms of listeriosis in humans. Both invasive and febrile
      gastroenteritis listeriosis is caused mostly by serotypes 1/2a, 1/2b and 4b
      strains. The outbreak strains of serotype 1/2a and 4b could be further classified
      into several epidemic clones but the genetic bases for the diverse
      pathophysiology have been unsuccessful. DNA microarray provides an important tool
      to scan the entire genome for genetic signatures that may distinguish the L.
      monocytogenes strains belonging to different outbreaks. We have designed a pan
      genomic microarray chip (Listeria GeneChip) containing sequences from 24 L.
      monocytogenes strains. The chip was designed to identify the presence/absence of
      genomic sequences, analyze transcription profiles and identify SNPs. Analysis of
      the genomic profiles of 38 outbreak strains representing 1/2a, 1/2b and 4b
      serotypes, revealed that the strains formed distinct genetic clusters adhering to
      their serotypes and epidemic clone types. Although serologically 1/2a and 1/b
      strains share common antigenic markers microarray analysis revealed that 1/2a
      strains are further apart from the closely related 1/2b and 4b strains. Within
      any given serotype and epidemic clone type the febrile gastroenteritis and
      invasive strains can be further distinguished based on several genetic markers
      including large numbers of phage genome, and intergenic sequences. Our results
      showed that the microarray-based data can be an important tool in
      characterization of L. monocytogenes strains involved in both invasive and
      gastroenteritis outbreaks. The results for the first time showed that the
      serotypes and epidemic clones are based on extensive pan-genomic variability and
      the 1/2b and 4bstrains are more closely related to each other than the 1/2a
      strains. The data also supported the hypothesis that the strains causing these
      two diverse outbreaks are genotypically different and this finding might be
      important in understanding the pathophysiology of this organism.

PMID- 22457725
TI  - MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide and induces
      its fibrillization.
AB  - Increasing evidence supports the contribution of local inflammation to the
      development of Alzheimer's disease (AD) pathology, although the precise
      mechanisms are not clear. In this study, we demonstrate that the pro-inflammatory
      protein S100A9 interacts with the Abeta1-40 peptide and promotes the formation of
      fibrillar beta-amyloid structures. This interaction also results in reduced
      S100A9 cytotoxicity by the binding of S100A9 toxic species to Abeta1-40 amyloid
      structures. These results suggest that secretion of S100A9 during inflammation
      promotes the formation of amyloid plaques. By acting as a sink for toxic species,
      plaque formation may be the result of a protective response within the brain of
      AD patients, in part mediated by S100A9.

PMID- 22457726
TI  - Exploitation of insect vibrational signals reveals a new method of pest
      management.
AB  - Food production is considered to be the main source of human impact on the
      environment and the concerns about detrimental effects of pesticides on
      biodiversity and human health are likely to lead to an increasingly restricted
      use of chemicals in agriculture. Since the first successful field trial,
      pheromone based mating disruption enabled sustainable insect control, which
      resulted in reduced levels of pesticide use. Organic farming is one of the
      fastest growing segments of agriculture and with the continuously growing public
      concern about use of pesticides, the main remaining challenge in increasing the
      safety of the global food production is to identify appropriate alternative
      mating disruption approaches for the numerous insect pests that do not rely on
      chemical communication. In the present study, we show for the first time that
      effective mating disruption based on substrate-borne vibrational signals can be
      achieved in the field. When disruptive vibrational signals were applied to
      grapevine plants through a supporting wire, mating frequency of the leafhopper
      pest Scaphoideus titanus dropped to 9 % in semi-field conditions and to 4 % in a
      mature vineyard. The underlying mechanism of this environmentally friendly pest
      control tactic is a masking of the vibrational signals used in mate recognition
      and location. Because vibrational communication is widespread in insects, mating
      disruption using substrate vibrations can transform many open field and
      greenhouse based farming systems.

PMID- 22457727
TI  - RUNX3 mediates suppression of tumor growth and metastasis of human CCRCC by
      regulating cyclin related proteins and TIMP-1.
AB  - Here we presented that the expression of RUNX3 was significantly decreased in 75
      cases of clear cell renal cell carcinoma (CCRCC) tissues (p<0.05). Enforced RUNX3
      expression mediated 786-O cells to exhibit inhibition of growth, G1 cell-cycle
      arrest and metastasis in vitro, and to lost tumorigenicity in nude mouse model in
      vivo. RUNX3-induced growth suppression was found partially to regulate various
      proteins, including inhibition of cyclinD1, cyclinE, cdk2, cdk4 and p-Rb, but
      increase of p27(Kip1), Rb and TIMP-1. Therefore, RUNX3 had the function of
      inhibiting the proliferative and metastatic abilities of CCRCC cells by
      regulating cyclins and TIMP1.

PMID- 22457729
TI  - Apology isn't good enough: an apology suppresses an approach motivation but not
      the physiological and psychological anger.
AB  - Although studies have emphasized the multiple components of anger, little is
      known about the physiological and psychological mechanisms of the approach
      motivational component and the negative emotional component of anger. In the
      present study, participants wrote brief opinions about social problems (e.g.,
      tuition hikes) and received a handwritten, insulting comment about their
      composition from the experimenter. Half of the participants (apology group)
      received a simple apologetic sentence at the end of the insulting comment. Half
      of the participants (no apology group) did not receive one. The physiological
      responses of the participants were recorded prior to, and after they read the
      comments. Increases in heart rate and asymmetric frontal brain activity were
      suppressed only in the apology group. Both groups showed an increase in skin
      conductance response. Our psychological scales showed that the apology suppressed
      self reported state anger from an approach-motivational standpoint but not from a
      negative emotional standpoint. The results suggest that anger is not a unitary
      process but has multiple components. The apology did provide a different
      physiological profile but did not dampen down the subjective experience of anger.
      Thus, providing an apology may not always be effective for alleviating the
      experience of anger to an insult.

PMID- 22457728
TI  - Hypoxia negatively regulates antimetastatic PEDF in melanoma cells by a hypoxia
      inducible factor-independent, autophagy dependent mechanism.
AB  - Pigment epithelium-derived factor (PEDF), a member of the serine protease
      inhibitor (SERPIN) superfamily, displays a potent antiangiogenic and
      antimetastatic activity in a broad range of tumor types. Melanocytes and low
      aggressive melanoma cells secrete high levels of PEDF, while its expression is
      lost in highly aggressive melanomas. PEDF efficiently abrogates a number of
      functional properties critical for the acquisition of metastatic ability by
      melanoma cells, such as neovascularization, proliferation, migration,
      invasiveness and extravasation. In this study, we identify hypoxia as a relevant
      negative regulator of PEDF in melanocytes and low aggressive melanoma cells. PEDF
      was regulated at the protein level. Importantly, although downregulation of PEDF
      was induced by inhibition of 2-oxoglutarate-dependent dioxygenases, it was
      independent of the hypoxia inducible factor (HIF), a key mediator of the
      adaptation to hypoxia. Decreased PEDF protein was not mediated by inhibition of
      translation through untranslated regions (UTRs) in melanoma cells. Degradation by
      metalloproteinases, implicated on PEDF degradation in retinal pigment epithelial
      cells, or by the proteasome, was also excluded as regulatory mechanism in
      melanoma cells. Instead, we found that degradation by autophagy was critical for
      PEDF downregulation under hypoxia in human melanoma cells. Our findings show that
      hypoxic conditions encountered during primary melanoma growth downregulate
      antiangiogenic and antimetastasic PEDF by a posttranslational mechanism involving
      degradation by autophagy and could therefore contribute to the acquisition of
      highly metastatic potential characteristic of aggressive melanoma cells.

PMID- 22457730
TI  - Subcellular localization of total and activated Src kinase in African American
      and Caucasian breast cancer.
AB  - BACKGROUND: Src, a non-receptor tyrosine kinase is elevated in cancer with
      expression and activity correlated with cell proliferation, adhesion, survival,
      motility, metastasis and angiogenesis. There is limited data on Src expression
      and subcellular localization in breast cancer and no information about expression
      in racial/ethnic groups. METHODOLOGY/PRINCIPAL FINDINGS: The present study
      evaluated Src expression, activity, and subcellular localization in triple
      negative breast cancer (TNBC) and ERalpha positive breast cancer (ER+BC), cancer
      tissue and adjacent normal epithelial ducts, and Caucasian and African American
      cases. 79 paraffin embedded breast carcinoma cases were obtained from Tulane
      University Hospital between 2007-2009. 39 cases represented TNBC (33-African
      Americans, 4-Caucasians, 2-unknowns) and 40 cases represented ER+BC (21-African
      Americans, 16-Caucasians, 3-unknowns). Immunohistochemistry was used to measure
      staining distribution and intensity of total Src and activated phospho-SrcY416 (p
      Y416Src) in carcinoma tissue and adjacent normal mammary ducts. In TNBC and
      ER+BC, total Src was significantly higher in cancer compared to adjacent normal
      ducts (P<0.0001) in both cell membrane and cytoplasm. In membranes, p-Y416Src was
      elevated in cancer compared to normal ducts. Total Src in the tumor cytoplasm was
      significantly higher in TNBC compared to ER+BC (P = 0.0028); conversely, p
      Y416Src in the tumor cell membranes was higher in TNBC compared to ER+BC (P =
      0.0106). Comparison between African American (n = 21) and Caucasian ER+BC (n =
      16) revealed no significant difference in expression and localization of total
      Src and p-Y416Src. TNBC cases positive for lymph node metastasis showed elevated
      membrane p-Y416Src compared to lymph node negative TNBC (P = 0.027).
      CONCLUSION/SIGNIFICANCE: Total Src and p-Y416Src were expressed higher in cancer
      compared to adjacent normal ducts. Cytoplasmic total Src and membrane p-Y416Src
      were significantly higher in TNBC compared to ER+BC. TNBC cases with lymph node
      metastasis showed elevated membrane p-Y416Src. Taken together, Src was elevated
      in the membrane and cytoplasm of more aggressive TNBC.

PMID- 22457732
TI  - Biomass of scyphozoan jellyfish, and its spatial association with 0-group fish in
      the Barents Sea.
AB  - An 0-group fish survey is conducted annually in the Barents Sea in order to
      estimate fish population abundance. Data on jellyfish by-catch have been recorded
      since 1980, although this dataset has never been analysed. In recent years,
      however, the ecological importance of jellyfish medusae has become widely
      recognized. In this paper the biomass of jellyfish (medusae) in 0-60 m depths is
      calculated for the period 1980-2010. During this period the climate changed from
      cold to warm, and changes in zooplankton and fish distribution and abundance were
      observed. This paper discusses the less well known ecosystem component; jellyfish
      medusae within the Phylum Cnidaria, and their spatial and temporal variation. The
      long term average was ca. 9*108 kg, with some years showing biomasses in excess
      of 5*109 kg. The biomasses were low during 1980s, increased during 1990s, and
      were highest in early 2000s with a subsequent decline. The bulk of the jellyfish
      were observed in the central parts of the Barents Sea, which is a core area for
      most 0-group fishes. Jellyfish were associated with haddock in the western area,
      with haddock and herring in the central and coastal area, and with capelin in the
      northern area of the Barents Sea. The jellyfish were present in the temperature
      interval 1 degrees C<T<10 degrees C, with peak densities at ca. 5.5 degrees C,
      and the greatest proportion of the jellyfish occurring between 4.0-7.0 degrees C.
      It seems that the ongoing warming trend may be favourable for Barents Sea
      jellyfish medusae; however their biomass has showed a recent moderate decline
      during years with record high temperatures in the Barents Sea. Jellyfish are
      undoubtedly an important component of the Barents Sea ecosystem, and the data
      presented here represent the best summary of jellyfish biomass and distribution
      yet published for the region.

PMID- 22457731
TI  - Pandemic influenza A H1N1 2009 infection versus vaccination: a cohort study
      comparing immune responses in pregnancy.
AB  - BACKGROUND: With the emergence of H1N1 pandemic (pH1N1) influenza, the CDC
      recommended that pregnant women be one of five initial target groups to receive
      the 2009 monovalent H1N1 vaccine, regardless of prior infection with this
      influenza strain. We sought to compare the immune response of pregnant women to
      H1N1 infection versus vaccination and to determine the extent of passive immunity
      conferred to the newborn. METHODS/FINDINGS: During the 2009-2010 influenza
      season, we enrolled a cohort of women who either had confirmed pH1N1 infection
      during pregnancy, did not have pH1N1 during pregnancy but were vaccinated against
      pH1N1, or did not have illness or vaccination. Maternal and umbilical cord venous
      blood samples were collected at delivery. Hemagglutination inhibition assays
      (HAI) for pH1N1 were performed. Data were analyzed using linear regression
      analyses. HAIs were performed for matched maternal/cord blood pairs for 16 women
      with confirmed pH1N1 infection, 14 women vaccinated against pH1N1, and 10 women
      without infection or vaccination. We found that pH1N1 vaccination and wild-type
      infection during pregnancy did not differ with respect to (1) HAI titers at
      delivery, (2) HAI antibody decay slopes over time, and (3) HAI titers in the cord
      blood. CONCLUSIONS: Vaccination against pH1N1 confers a similar HAI antibody
      response as compared to pH1N1 infection during pregnancy, both in quantity and
      quality. Illness or vaccination during pregnancy confers passive immunity to the
      newborn.

PMID- 22457733
TI  - Advantage of hole stimulus in rivalry competition.
AB  - Mounting psychophysical evidence suggests that early visual computations are
      sensitive to the topological properties of stimuli, such as the determination of
      whether the object has a hole or not. Previous studies have demonstrated that the
      hole feature took some advantages during conscious perception. In this study, we
      investigate whether there exists a privileged processing for hole stimuli during
      unconscious perception. By applying a continuous flash suppression paradigm, the
      target was gradually introduced to one eye to compete against a flashed full
      contrast Mondrian pattern which was presented to the other eye. This method
      ensured that the target image was suppressed during the initial perceptual
      period. We compared the initial suppressed duration between the stimuli with and
      without the hole feature and found that hole stimuli required less time than no
      hole stimuli to gain dominance against the identical suppression noise. These
      results suggest the hole feature could be processed in the absence of awareness,
      and there exists a privileged detection of hole stimuli during suppressed phase
      in the interocular rivalry.

PMID- 22457734
TI  - Incidence of H1N1 2009 virus infection through the analysis of paired plasma
      specimens among blood donors, France.
AB  - BACKGROUND: Knowledge of the age-specific prevalence of seroprotection and
      incidence of seroconversion infection is necessary to complement clinical
      surveillance data and statistical models. It provides the basis for estimating
      the future impact of influenza A (H1N1pdm09) and implementing appropriate
      prevention and response strategies. METHODS: Using a cross-sectional design, two
      stage stratified sampling and paired plasma samples, we estimated the age
      specific prevalence of a protective level of H1N1pdm09 antibodies in the French
      adult population before and after the 2009/10 pandemic, and the proportion of
      those susceptible that seroconverted due to infection, from a single sample of
      1,936 blood donors aged 20-70 years in mainland France in June 2010. Samples with
      a haemagglutination inhibition (HI) titre >=1?40 were considered seropositive,
      and seroconversion due to infection was defined as a 4-fold increase in titre in
      the absence of H1N1pdm09 vaccination or pre-pandemic seropositivity. RESULTS: Out
      of the 1,936 donors, 1,708 were included in the analysis. Seroprevalence before
      the pandemic was 6.7% (95% CI 5.0, 8.9) with no significant differences by age
      group (p = 0.3). Seroprevalence afterwards was 23.0% (95% CI 17.7, 29.3) with 20
      29 year olds having a higher level than older groups (p<0.001). Seroconversion
      due to infection was 12.2% (95% CI 6.9, 20.5). Younger age-group, vaccination
      against H1N1 and being seropositive before the pandemic were strongly associated
      with post-pandemic seropositivity. CONCLUSIONS: Before the 2009/2010 winter
      influenza season, only 6.7% of the French mainland population aged 20-70 had a
      level of antibodies usually considered protective. During the first pandemic
      wave, 12.2% of the population seroconverted due to infection and the
      seroprevalence after the wave rose to 23%, either due to prepandemic
      seropositivity, infection or vaccination. This relatively low latter figure
      contributed to an extension of target groups for influenza vaccination for the
      2010/2011 season.

PMID- 22457735
TI  - The US distribution of physicians from lower income countries.
AB  - INTRODUCTION: Since the 1960 s, the number of international medical graduates
      (IMGs) in the United States has increased significantly. Given concerns regarding
      the effects of this loss to their countries of origin, the authors undertook a
      study of IMGs from lower income countries currently practicing in the United
      States. METHODS: The AMA Physician Masterfile was accessed to identify all
      265,851 IMGs in active practice in the United States. These were divided by state
      of practice and country of origin. World Bank income classification was used to
      identify lower income countries. RESULTS: 128,729 IMGs were identified from 53
      lower income countries, constituting 15 percent of the US active physician
      workforce. As a percentage of the workforce, West Virginia (29%), New Jersey
      (27%), and Michigan (26%) had the most IMGs from lower income countries, and
      Montana, Idaho, and Alaska (all less than 2%), the least. The countries with the
      greatest loss of physicians to the United States per 100,000 population were the
      Philippines, Syria, Jordan, and Haiti. DISCUSSION: The reliance of US medicine on
      physicians from lower income countries is beneficial to the United States both
      clinically and economically. However, it results in a loss of the lower income
      country's investment in the IMG's education. We discuss possible mechanisms to
      compensate the lower income countries for the medical education costs of their
      physicians who immigrate to the US.

PMID- 22457736
TI  - Memory for semantically related and unrelated declarative information: the
      benefit of sleep, the cost of wake.
AB  - Numerous studies have examined sleep's influence on a range of hippocampus
      dependent declarative memory tasks, from text learning to spatial navigation. In
      this study, we examined the impact of sleep, wake, and time-of-day influences on
      the processing of declarative information with strong semantic links
      (semantically related word pairs) and information requiring the formation of
      novel associations (unrelated word pairs). Participants encoded a set of related
      or unrelated word pairs at either 9 am or 9 pm, and were then tested after an
      interval of 30 min, 12 hr, or 24 hr. The time of day at which subjects were
      trained had no effect on training performance or initial memory of either word
      pair type. At 12 hr retest, memory overall was superior following a night of
      sleep compared to a day of wakefulness. However, this performance difference was
      a result of a pronounced deterioration in memory for unrelated word pairs across
      wake; there was no sleep-wake difference for related word pairs. At 24 hr retest,
      with all subjects having received both a full night of sleep and a full day of
      wakefulness, we found that memory was superior when sleep occurred shortly after
      learning rather than following a full day of wakefulness. Lastly, we present
      evidence that the rate of deterioration across wakefulness was significantly
      diminished when a night of sleep preceded the wake period compared to when no
      sleep preceded wake, suggesting that sleep served to stabilize the memories
      against the deleterious effects of subsequent wakefulness. Overall, our results
      demonstrate that 1) the impact of 12 hr of waking interference on memory
      retention is strongly determined by word-pair type, 2) sleep is most beneficial
      to memory 24 hr later if it occurs shortly after learning, and 3) sleep does in
      fact stabilize declarative memories, diminishing the negative impact of
      subsequent wakefulness.

PMID- 22457737
TI  - Deregulation of sucrose-controlled translation of a bZIP-type transcription
      factor results in sucrose accumulation in leaves.
AB  - Sucrose is known to repress the translation of Arabidopsis thaliana AtbZIP11
      transcript which encodes a protein belonging to the group of S (S--stands for
      small) basic region-leucine zipper (bZIP)-type transcription factor. This
      repression is called sucrose-induced repression of translation (SIRT). It is
      mediated through the sucrose-controlled upstream open reading frame (SC-uORF)
      found in the AtbZIP11 transcript. The SIRT is reported for 4 other genes
      belonging to the group of S bZIP in Arabidopsis. Tobacco tbz17 is
      phylogenetically closely related to AtbZIP11 and carries a putative SC-uORF in
      its 5'-leader region. Here we demonstrate that tbz17 exhibits SIRT mediated by
      its SC-uORF in a manner similar to genes belonging to the S bZIP group of the
      Arabidopsis genus. Furthermore, constitutive transgenic expression of tbz17
      lacking its 5'-leader region containing the SC-uORF leads to production of
      tobacco plants with thicker leaves composed of enlarged cells with 3-4 times
      higher sucrose content compared to wild type plants. Our finding provides a novel
      strategy to generate plants with high sucrose content.

PMID- 22457738
TI  - Outcomes of TB treatment by HIV status in national recording systems in Brazil,
      2003-2008.
AB  - BACKGROUND: Although the Brazilian national reporting system for tuberculosis
      cases (SINAN) has enormous potential to generate data for policy makers, formal
      assessments of treatment outcomes and other aspects of TB morbidity and mortality
      are not produced with enough depth and rigor. In particular, the effect of HIV
      status on these outcomes has not been fully explored, partly due to incomplete
      recording in the national database. METHODOLOGY/PRINCIPAL FINDINGS: In a
      retrospective cohort study, we assessed TB treatment outcomes, including rates of
      cure, default, mortality, transfer and multidrug resistant TB (MDR-TB) among a
      purposively chosen sample of 161,481 new cases reported in SINAN between 2003 and
      2008. The study population included all new cases reported in the six States with
      the highest level of completeness of the HIV status field in the system. These
      cases were mostly male (67%), white (62%), had pulmonary TB (79%) and a suspect
      chest X ray (83%). Treatment outcomes were best for those HIV negative cases and
      worst for those known HIV positive patients (cure rate of 85.7% and 55.7%
      respectively). In multivariate modeling, the risk of having an unfavorable
      outcome (all outcomes except cure) was 3.09 times higher for those HIV positive
      compared with those HIV negative (95% CI 3.02-3.16). The risk of death and
      default also increased with HIV positivity. The group without a known HIV status
      showed intermediate outcomes between the groups above, suggesting that this group
      includes some with HIV infection. CONCLUSIONS: HIV status played an important
      role in TB treatment outcomes in the study period. The outcomes observed in those
      with known HIV were poor and need to be improved. Those in the group with unknown
      HIV status indicate the need for wider HIV testing among new TB cases.

PMID- 22457739
TI  - Impact of normothermic preservation with extracellular type solution containing
      trehalose on rat kidney grafting from a cardiac death donor.
AB  - BACKGROUND: The aim of this study was to investigate factors that may improve the
      condition of a marginal kidney preserved with a normothermic solution following
      cardiac death (CD) in a model of rat kidney transplantation (RTx). METHODS: Post
      euthanasia, Lewis (LEW) donor rats were left for 1 h in a 23 degrees C room.
      These critical kidney grafts were preserved in University of Wisconsin (UW),
      lactate Ringer's (LR), or extracellular-trehalose-Kyoto (ETK) solution, followed
      by intracellular-trehalose-Kyoto (ITK) solution at 4, 23, or 37 degrees C for
      another 1 h, and finally transplanted into bilaterally nephrectomized LEW
      recipient rats (n = 4-6). Grafts of rats surviving to day 14 after RTx were
      evaluated by histopathological examination. The energy activity of these marginal
      rat kidneys was measured by high-performance liquid chromatography (HPLC; n = 4
      per group) and fluorescence intensity assay (n = 6 per group) after preservation
      with UW or ETK solutions at each temperature. Finally, the transplanted kidney
      was assessed by an in vivo luciferase imaging system (n = 2). RESULTS: Using the
      1-h normothermic preservation of post-CD kidneys, five out of six recipients in
      the ETK group survived until 14 days, in contrast to zero out of six in the UW
      group (p<0.01). Preservation with ITK rather than ETK at 23 degrees C tended to
      have an inferior effect on recipient survival (p = 0.12). Energy activities of
      the fresh donor kidneys decreased in a temperature-dependent manner, while those
      of post-CD kidneys remained at the lower level. ETK was superior to UW in
      protecting against edema of the post-CD kidneys at the higher temperature.
      Luminescence intensity of successful grafts recovered within 1 h, while the
      intensity of grafts of deceased recipients did not change at 1 h post
      reperfusion. CONCLUSIONS: Normothermic storage with extracellular-type solution
      containing trehalose might prevent reperfusion injury due to temperature
      dependent tissue edema.

PMID- 22457740
TI  - Microfluidic chip for molecular amplification of influenza A RNA in human
      respiratory specimens.
AB  - A rapid, low cost, accurate point-of-care (POC) device to detect influenza virus
      is needed for effective treatment and control of both seasonal and pandemic
      strains. We developed a single-use microfluidic chip that integrates solid phase
      extraction (SPE) and molecular amplification via a reverse transcription
      polymerase chain reaction (RT-PCR) to amplify influenza virus type A RNA. We
      demonstrated the ability of the chip to amplify influenza A RNA in human
      nasopharyngeal aspirate (NPA) and nasopharyngeal swab (NPS) specimens collected
      at two clinical sites from 2008-2010. The microfluidic test was dramatically more
      sensitive than two currently used rapid immunoassays and had high specificity
      that was essentially equivalent to the rapid assays and direct fluorescent
      antigen (DFA) testing. We report 96% (CI 89%,99%) sensitivity and 100% (CI
      95%,100%) specificity compared to conventional (bench top) RT-PCR based on the
      testing of n = 146 specimens (positive predictive value = 100%(CI 94%,100%) and
      negative predictive value = 96%(CI 88%,98%)). These results compare well with DFA
      performed on samples taken during the same time period (98% (CI 91%,100%)
      sensitivity and 96%(CI 86%,99%) specificity compared to our gold standard
      testing). Rapid immunoassay tests on samples taken during the enrollment period
      were less reliable (49%(CI 38%,61%) sensitivity and 98%(CI 98%,100%)
      specificity). The microfluidic test extracted and amplified influenza A RNA
      directly from clinical specimens with viral loads down to 103 copies/ml in 3 h or
      less. The new test represents a major improvement over viral culture in terms of
      turn around time, over rapid immunoassay tests in terms of sensitivity, and over
      bench top RT-PCR and DFA in terms of ease of use and portability.

PMID- 22457741
TI  - Predicting future clinical changes of MCI patients using longitudinal and
      multimodal biomarkers.
AB  - Accurate prediction of clinical changes of mild cognitive impairment (MCI)
      patients, including both qualitative change (i.e., conversion to Alzheimer's
      disease (AD)) and quantitative change (i.e., cognitive scores) at future time
      points, is important for early diagnosis of AD and for monitoring the disease
      progression. In this paper, we propose to predict future clinical changes of MCI
      patients by using both baseline and longitudinal multimodality data. To do this,
      we first develop a longitudinal feature selection method to jointly select brain
      regions across multiple time points for each modality. Specifically, for each
      time point, we train a sparse linear regression model by using the imaging data
      and the corresponding clinical scores, with an extra 'group regularization' to
      group the weights corresponding to the same brain region across multiple time
      points together and to allow for selection of brain regions based on the strength
      of multiple time points jointly. Then, to further reflect the longitudinal
      changes on the selected brain regions, we extract a set of longitudinal features
      from the original baseline and longitudinal data. Finally, we combine all
      features on the selected brain regions, from different modalities, for prediction
      by using our previously proposed multi-kernel SVM. We validate our method on 88
      ADNI MCI subjects, with both MRI and FDG-PET data and the corresponding clinical
      scores (i.e., MMSE and ADAS-Cog) at 5 different time points. We first predict the
      clinical scores (MMSE and ADAS-Cog) at 24-month by using the multimodality data
      at previous time points, and then predict the conversion of MCI to AD by using
      the multimodality data at time points which are at least 6-month ahead of the
      conversion. The results on both sets of experiments show that our proposed method
      can achieve better performance in predicting future clinical changes of MCI
      patients than the conventional methods.

PMID- 22457742
TI  - Multi-level communication of human retinal pigment epithelial cells via tunneling
      nanotubes.
AB  - BACKGROUND: Tunneling nanotubes (TNTs) may offer a very specific and effective
      way of intercellular communication. Here we investigated TNTs in the human
      retinal pigment epithelial (RPE) cell line ARPE-19. Morphology of TNTs was
      examined by immunostaining and scanning electron microscopy. To determine the
      function of TNTs between cells, we studied the TNT-dependent intercellular
      communication at different levels including electrical and calcium signalling,
      small molecular diffusion as well as mitochondrial re-localization. Further,
      intercellular organelles transfer was assayed by FACS analysis. METHODOLOGY AND
      PRINCIPAL FINDINGS: Microscopy showed that cultured ARPE-19 cells are frequently
      connected by TNTs, which are not attached to the substratum. The TNTs were
      straight connections between cells, had a typical diameter of 50 to 300 nm and a
      length of up to 120 um. We observed de novo formation of TNTs by diverging from
      migrating cells after a short time of interaction. Scanning electron microscopy
      confirmed characteristic features of TNTs. Fluorescence microscopy revealed that
      TNTs between ARPE-19 cells contain F-actin but no microtubules. Depolymerisation
      of F-actin, induced by addition of latrunculin-B, led to disappearance of TNTs.
      Importantly, these TNTs could function as channels for the diffusion of small
      molecules such as Lucifer Yellow, but not for large molecules like Dextran Red.
      Further, organelle exchange between cells via TNTs was observed by microscopy.
      Using Ca2+ imaging we show the intercellular transmission of calcium signals
      through TNTs. Mechanical stimulation led to membrane depolarisation, which expand
      through TNT connections between ARPE-19 cells. We further demonstrate that TNTs
      can mediate electrical coupling between distant cells. Immunolabelling for Cx43
      showed that this gap junction protein is interposed at one end of 44% of TNTs
      between ARPE-19 cells. CONCLUSIONS AND SIGNIFICANCE: Our observations indicate
      that human RPE cell line ARPE-19 cells communicate by tunneling nanotubes and can
      support different types of intercellular traffic.

PMID- 22457743
TI  - Validation study of existing gene expression signatures for anti-TNF treatment in
      patients with rheumatoid arthritis.
AB  - So far, there are no means of identifying rheumatoid arthritis (RA) patients who
      will fail to respond to tumour necrosis factor blocking agents (anti-TNF), prior
      to treatment. We set out to validate eight previously reported gene expression
      signatures predicting therapy outcome. Genome-wide expression profiling using
      Affymetrix GeneChip Exon 1.0 ST arrays was performed on RNA isolated from whole
      blood of 42 RA patients starting treatment with infliximab or adalimumab.
      Clinical response according to EULAR criteria was determined at week 14 of
      therapy. Genes that have been reported to be associated with anti-TNF treatment
      were extracted from our dataset. K-means partition clustering was performed to
      assess the predictive value of the gene-sets. We performed a hypothesis-driven
      analysis of the dataset using eight existing gene sets predictive of anti-TNF
      treatment outcome. The set that performed best reached a sensitivity of 71% and a
      specificity of 61%, for classifying the patients in the current study. We
      successfully validated one of eight previously reported predictive expression
      profile. This replicated expression signature is a good starting point for
      developing a prediction model for anti-TNF treatment outcome that can be used in
      a daily clinical setting. Our results confirm that gene expression profiling
      prior to treatment is a useful tool to predict anti-TNF (non) response.

PMID- 22457744
TI  - Electrical pulse stimulation of cultured human skeletal muscle cells as an in
      vitro model of exercise.
AB  - BACKGROUND AND AIMS: Physical exercise leads to substantial adaptive responses in
      skeletal muscles and plays a central role in a healthy life style. Since exercise
      induces major systemic responses, underlying cellular mechanisms are difficult to
      study in vivo. It was therefore desirable to develop an in vitro model that would
      resemble training in cultured human myotubes. METHODS: Electrical pulse
      stimulation (EPS) was applied to adherent human myotubes. Cellular contents of
      ATP, phosphocreatine (PCr) and lactate were determined. Glucose and oleic acid
      metabolism were studied using radio-labeled substrates, and gene expression was
      analyzed using real-time RT-PCR. Mitochondrial content and function were measured
      by live imaging and determination of citrate synthase activity, respectively.
      Protein expression was assessed by electrophoresis and immunoblotting. RESULTS:
      High-frequency, acute EPS increased deoxyglucose uptake and lactate production,
      while cell contents of both ATP and PCr decreased. Chronic, low-frequency EPS
      increased oxidative capacity of cultured myotubes by increasing glucose
      metabolism (uptake and oxidation) and complete fatty acid oxidation. mRNA
      expression level of pyruvate dehydrogenase complex 4 (PDK4) was significantly
      increased in EPS-treated cells, while mRNA expressions of interleukin 6 (IL-6),
      cytochrome C and carnitin palmitoyl transferase b (CPT1b) also tended to
      increase. Intensity of MitoTracker(r)Red FM was doubled after 48 h of chronic,
      low-frequency EPS. Protein expression of a slow fiber type marker (MHCI) was
      increased in EPS-treated cells. CONCLUSIONS: Our results imply that in vitro EPS
      (acute, high-frequent as well as chronic, low-frequent) of human myotubes may be
      used to study effects of exercise.

PMID- 22457745
TI  - Gestational weight gain and body mass index in children: results from three
      german cohort studies.
AB  - INTRODUCTION: Previous studies suggested potential priming effects of gestational
      weight gain (GWG) on offspring's body composition in later life. However,
      consistency of these effects in normal weight, overweight and obese mothers is
      less clear. METHODS: We combined the individual data of three German cohorts and
      assessed associations of total and excessive GWG (as defined by criteria of the
      Institute of Medicine) with offspring's mean body mass index (BMI) standard
      deviation scores (SDS) and overweight at the age of 5-6 years (total: n = 6,254).
      Quantile regression was used to examine potentially different effects on
      different parts of the BMI SDS distribution. All models were adjusted for birth
      weight, maternal age and maternal smoking during pregnancy and stratified by
      maternal pre-pregnancy weight status. RESULTS: In adjusted models, positive
      associations of total and excessive GWG with mean BMI SDS and overweight were
      observed only in children of non- overweight mothers. For example, excessive GWG
      was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS
      (0.13 (0.02, 0.24) kg/m(2) of 'real' BMI) in children of normal-weight mothers.
      The effects of total and excessive GWG on BMI SDS increased for higher- BMI
      children of normal-weight mothers. DISCUSSION: Increased GWG is likely to be
      associated with overweight in offspring of non-overweight mothers.

PMID- 22457746
TI  - One-step derivation of mesenchymal stem cell (MSC)-like cells from human
      pluripotent stem cells on a fibrillar collagen coating.
AB  - Controlled differentiation of human embryonic stem cells (hESCs) and induced
      pluripotent stem cells (iPSCs) into cells that resemble adult mesenchymal stem
      cells (MSCs) is an attractive approach to obtain a readily available source of
      progenitor cells for tissue engineering. The present study reports a new method
      to rapidly derive MSC-like cells from hESCs and hiPSCs, in one step, based on
      culturing the cells on thin, fibrillar, type I collagen coatings that mimic the
      structure of physiological collagen. Human H9 ESCs and HDFa-YK26 iPSCs were
      singly dissociated in the presence of ROCK inhibitor Y-27632, plated onto
      fibrillar collagen coated plates and cultured in alpha minimum essential medium
      (alpha-MEM) supplemented with 10% fetal bovine serum, 50 uM magnesium L-ascorbic
      acid phosphate and 100 nM dexamethasone. While fewer cells attached on the
      collagen surface initially than standard tissue culture plastic, after culturing
      for 10 days, resilient colonies of homogenous spindle-shaped cells were obtained.
      Flow cytometric analysis showed that a high percentage of the derived cells
      expressed typical MSC surface markers including CD73, CD90, CD105, CD146 and
      CD166 and were negative as expected for hematopoietic markers CD34 and CD45. The
      MSC-like cells derived from pluripotent cells were successfully differentiated in
      vitro into three different lineages: osteogenic, chondrogenic, and adipogenic.
      Both H9 hES and YK26 iPS cells displayed similar morphological changes during the
      derivation process and yielded MSC-like cells with similar properties. In
      conclusion, this study demonstrates that bioimimetic, fibrillar, type I collagen
      coatings applied to cell culture plates can be used to guide a rapid, efficient
      derivation of MSC-like cells from both human ES and iPS cells.

PMID- 22457747
TI  - Copy number variation affecting the Photoperiod-B1 and Vernalization-A1 genes is
      associated with altered flowering time in wheat (Triticum aestivum).
AB  - The timing of flowering during the year is an important adaptive character
      affecting reproductive success in plants and is critical to crop yield. Flowering
      time has been extensively manipulated in crops such as wheat (Triticum aestivum
      L.) during domestication, and this enables them to grow productively in a wide
      range of environments. Several major genes controlling flowering time have been
      identified in wheat with mutant alleles having sequence changes such as
      insertions, deletions or point mutations. We investigated genetic variants in
      commercial varieties of wheat that regulate flowering by altering photoperiod
      response (Ppd-B1 alleles) or vernalization requirement (Vrn-A1 alleles) and for
      which no candidate mutation was found within the gene sequence. Genetic and
      genomic approaches showed that in both cases alleles conferring altered flowering
      time had an increased copy number of the gene and altered gene expression.
      Alleles with an increased copy number of Ppd-B1 confer an early flowering day
      neutral phenotype and have arisen independently at least twice. Plants with an
      increased copy number of Vrn-A1 have an increased requirement for vernalization
      so that longer periods of cold are required to potentiate flowering. The results
      suggest that copy number variation (CNV) plays a significant role in wheat
      adaptation.

PMID- 22457748
TI  - Towards endometriosis diagnosis by gadofosveset-trisodium enhanced magnetic
      resonance imaging.
AB  - Endometriosis is defined as the presence of endometrial tissue outside the
      uterus. It affects 10-15% of women during reproductive age and has a big personal
      and social impact due to chronic pelvic pain, subfertility, loss of work-hours
      and medical costs. Such conditions are exacerbated by the fact that the correct
      diagnosis is made as late as 8-11 years after symptom presentation. This is due
      to the lack of a reliable non-invasive diagnostic test and the fact that the
      reference diagnostic standard is laparoscopy (invasive, expensive and not without
      risks). High-molecular weight gadofosveset-trisodium is used as contrast agent in
      Magnetic Resonance Imaging (MRI). Since it extravasates from hyperpermeable
      vessels more easily than from mature blood vessels, this contrast agent detects
      angiogenesis efficiently. Endometriosis has high angiogenic activity. Therefore,
      we have tested the possibility to detect endometriosis non-invasively using
      Dynamic Contrast-Enhanced MRI (DCE-MRI) and gadofosveset-trisodium as a contrast
      agent in a mouse model. Endometriotic lesions were surgically induced in nine
      mice by autologous transplantation. Three weeks after lesion induction, mice were
      scanned by DCE-MRI. Dynamic image analysis showed that the rates of uptake
      (inwash), persistence and outwash of the contrast agent were different between
      endometriosis and control tissues (large blood vessels and back muscle). Due to
      the extensive angiogenesis in induced lesions, the contrast agent persisted
      longer in endometriotic than control tissues, thus enhancing the MRI signal
      intensity. DCE-MRI was repeated five weeks after lesion induction, and contrast
      enhancement was similar to that observed three weeks after endometriosis
      induction. The endothelial-cell marker CD31 and the pericyte marker alpha-smooth
      muscle-actin (mature vessels) were detected with immunohistochemistry and
      confirmed that endometriotic lesions had significantly higher prevalence of new
      vessels (CD31 only positive) than the uterus and control tissues. The diagnostic
      value of gadofosveset-trisodium to detect endometriosis should be tested in human
      settings.

PMID- 22457749
TI  - Sociodemographic and disease correlates of body image distress among patients
      with systemic sclerosis.
AB  - BACKGROUND: Body image concerns are infrequently studied in systemic sclerosis
      (SSc), even though significant visible disfigurement is common. The objective of
      this study was to identify sociodemographic and disease-related correlates of
      dissatisfaction with appearance and social discomfort among people with SSc.
      METHODS: SSc patients came from the 15-center Canadian Scleroderma Research Group
      Registry. Sociodemographic information was based on patient self-report. Disease
      characteristics were obtained via physician examinations. The Brief-SWAP was used
      to assess dissatisfaction with appearance and social discomfort. Structural
      equation models were conducted with MPlus to determine the relationship of
      dissatisfaction with appearance and social discomfort with age, sex, education,
      marital status, race/ethnicity, disease duration, skin involvement,
      telangiectasias, skin pigmentation changes, and hand contractures. RESULTS: A
      total of 489 SSc patients (432 female, 57 male) were included. Extent of skin
      involvement was significantly associated with both dissatisfaction with
      appearance and social discomfort (standardized regression coefficients = 0.02, p
      = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face
      (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was
      robustly associated with younger age (-0.017, p<0.001) and upper-body
      telangiectasias (0.32, p = 0.021). Dissatisfaction with appearance was associated
      with hand contractures (0.07, p = 0.036). CONCLUSION: This study found that
      dissatisfaction with appearance and social discomfort were associated with
      numerous disfiguring characteristics of SSc, in addition to age. These results
      underline that there are multiple factors contributing to body image distress in
      SSc, as well as the need to attend to both disease and social contexts in
      understanding the impact of disfigurement among patients.

PMID- 22457750
TI  - Leukocytes are recruited through the bronchial circulation to the lung in a
      spontaneously hypertensive rat model of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) kills approximately 2.8 million
      people each year, and more than 80% of COPD cases can be attributed to smoking.
      Leukocytes recruited to the lung contribute to COPD pathology by releasing
      reactive oxygen metabolites and proteolytic enzymes. In this work, we
      investigated where leukocytes enter the lung in the early stages of COPD in order
      to better understand their effect as a contributor to the development of COPD. We
      simultaneously evaluated the parenchyma and airways for neutrophil accumulation,
      as well as increases in the adhesion molecules and chemokines that cause
      leukocyte recruitment in the early stages of tobacco smoke induced lung disease.
      We found neutrophil accumulation and increased expression of adhesion molecules
      and chemokines in the bronchial blood vessels that correlated with the
      accumulation of leukocytes recovered from the lung. The expression of adhesion
      molecules and chemokines in other vascular beds did not correlate with leukocytes
      recovered in bronchoalveolar lavage fluid (BALF). These data strongly suggest
      leukocytes are recruited in large measure through the bronchial circulation in
      response to tobacco smoke. Our findings have important implications for
      understanding the etiology of COPD and suggest that pharmaceuticals designed to
      reduce leukocyte recruitment through the bronchial circulation may be a potential
      therapy to treat COPD.

PMID- 22457751
TI  - Characterizing the collective personality of ant societies: aggressive colonies
      do not abandon their home.
AB  - Animal groups can show consistent behaviors or personalities just like solitary
      animals. We studied the collective behavior of Temnothorax nylanderi ant
      colonies, including consistency in behavior and correlations between different
      behavioral traits. We focused on four collective behaviors (aggression against
      intruders, nest relocation, removal of infected corpses and nest reconstruction)
      and also tested for links to the immune defense level of a colony and a fitness
      component (per-capita productivity). Behaviors leading to an increased exposure
      of ants to micro-parasites were expected to be positively associated with immune
      defense measures and indeed colonies that often relocated to other nest sites
      showed increased immune defense levels. Besides, colonies that responded with low
      aggression to intruders or failed to remove infected corpses, showed a higher
      likelihood to move to a new nest site. This resembles the trade-off between
      aggression and relocation often observed in solitary animals. Finally, one of the
      behaviors, nest reconstruction, was positively linked to per-capita productivity,
      whereas other colony-level behaviors, such as aggression against intruders,
      showed no association, albeit all behaviors were expected to be important for
      fitness under field conditions. In summary, our study shows that ant societies
      exhibit complex personalities that can be associated to the physiology and
      fitness of the colony. Some of these behaviors are linked in suites of correlated
      behaviors, similar to personalities of solitary animals.

PMID- 22457752
TI  - A common SMAD7 variant is associated with risk of colorectal cancer: evidence
      from a case-control study and a meta-analysis.
AB  - BACKGROUND: A common genetic variant, rs4939827, located in SMAD7, was identified
      by two recent genome-wide association (GWA) studies to be strongly associated
      with the risk of colorectal cancer (CRC). However, the following replication
      studies yielded conflicting results. METHOD AND FINDINGS: We conducted a case
      control study of 641 cases and 1037 controls in a Chinese population and then
      performed a meta-analysis, integrating our and published data of 34313 cases and
      33251 controls, to clarify the relationship between rs4939827 and CRC risk. In
      our case-control study, the dominant model was significant associated with
      increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI),
      1.19-1.80]. The following meta-analysis further confirmed this significant
      association for all genetic models but with significant between-study
      heterogeneity (all P for heterogeneity <0.1). By stratified analysis, we revealed
      that ethnicity, sample size, and tumor sites might constitute the source of
      heterogeneity. The cumulative analysis suggested that evident tendency to
      significant association was seen with adding study samples over time; whilst,
      sensitive analysis showed results before and after removal of each study were
      similar, indicating the highly stability of the current results. CONCLUSION:
      Results from our case-control study and the meta-analysis collectively confirmed
      the significant association of the variant rs4939827 with increased risk of
      colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined
      by rs4939287 should be imposed to reveal causal variant.

PMID- 22457753
TI  - Rationalization and design of the complementarity determining region sequences in
      an antibody-antigen recognition interface.
AB  - Protein-protein interactions are critical determinants in biological systems.
      Engineered proteins binding to specific areas on protein surfaces could lead to
      therapeutics or diagnostics for treating diseases in humans. But designing
      epitope-specific protein-protein interactions with computational atomistic
      interaction free energy remains a difficult challenge. Here we show that, with
      the antibody-VEGF (vascular endothelial growth factor) interaction as a model
      system, the experimentally observed amino acid preferences in the antibody
      antigen interface can be rationalized with 3-dimensional distributions of
      interacting atoms derived from the database of protein structures. Machine
      learning models established on the rationalization can be generalized to design
      amino acid preferences in antibody-antigen interfaces, for which the experimental
      validations are tractable with current high throughput synthetic antibody display
      technologies. Leave-one-out cross validation on the benchmark system yielded the
      accuracy, precision, recall (sensitivity) and specificity of the overall binary
      predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall
      Matthews correlation coefficient of the 20 amino acid types in the 24 interface
      CDR positions was 0.312. The structure-based computational antibody design
      methodology was further tested with other antibodies binding to VEGF. The results
      indicate that the methodology could provide alternatives to the current antibody
      technologies based on animal immune systems in engineering therapeutic and
      diagnostic antibodies against predetermined antigen epitopes.

PMID- 22457754
TI  - Motor simulation without motor expertise: enhanced corticospinal excitability in
      visually experienced dance spectators.
AB  - The human "mirror-system" is suggested to play a crucial role in action
      observation and execution, and is characterized by activity in the premotor and
      parietal cortices during the passive observation of movements. The previous motor
      experience of the observer has been shown to enhance the activity in this
      network. Yet visual experience could also have a determinant influence when
      watching more complex actions, as in dance performances. Here we tested the
      impact visual experience has on motor simulation when watching dance, by
      measuring changes in corticospinal excitability. We also tested the effects of
      empathic abilities. To fully match the participants' long-term visual experience
      with the present experimental setting, we used three live solo dance
      performances: ballet, Indian dance, and non-dance. Participants were either
      frequent dance spectators of ballet or Indian dance, or "novices" who never
      watched dance. None of the spectators had been physically trained in these dance
      styles. Transcranial magnetic stimulation was used to measure corticospinal
      excitability by means of motor-evoked potentials (MEPs) in both the hand and the
      arm, because the hand is specifically used in Indian dance and the arm is
      frequently engaged in ballet dance movements. We observed that frequent ballet
      spectators showed larger MEP amplitudes in the arm muscles when watching ballet
      compared to when they watched other performances. We also found that the higher
      Indian dance spectators scored on the fantasy subscale of the Interpersonal
      Reactivity Index, the larger their MEPs were in the arms when watching Indian
      dance. Our results show that even without physical training, corticospinal
      excitability can be enhanced as a function of either visual experience or the
      tendency to imaginatively transpose oneself into fictional characters. We suggest
      that spectators covertly simulate the movements for which they have acquired
      visual experience, and that empathic abilities heighten motor resonance during
      dance observation.

PMID- 22457755
TI  - Induction of the GABA cell phenotype: an in vitro model for studying
      neurodevelopmental disorders.
AB  - Recent studies of the hippocampus have suggested that a network of genes is
      associated with the regulation of the GAD67 (GAD1) expression and may play a role
      in gamma-amino butyric acid (GABA) dysfunction in schizophrenia (SZ) and bipolar
      disorder (BD). To obtain a more detailed understanding of how GAD67 regulation
      may result in GABAergic dysfunction, we have developed an in vitro model in which
      GABA cells are differentiated from the hippocampal precursor cell line, HiB5.
      Growth factors, such as PDGF, and BDNF, regulate the GABA phenotype by inducing
      the expression of GAD67 and stimulating the growth of cellular processes, many
      with growth cones that form appositions with the cell bodies and processes of
      other GAD67-positive cells. These changes are associated with increased
      expression of acetylated tubulin, microtubule-associated protein 2 (MAP2) and the
      post-synaptic density protein 95 (PSD95). The addition of BDNF, together with
      PDGF, increases the levels of mRNA and protein for GAD67, as well as the high
      affinity GABA uptake protein, GAT1. These changes are associated with increased
      concentrations of GABA in the cytoplasm of "differentiated" HiB5 neurons. In the
      presence of Ca2+ and K+, newly synthesized GABA is released extracellularly. When
      the HiB5 cells appear to be fully differentiated, they also express GAD65,
      parvalbumin and calbindin, and GluR subtypes as well as HDAC1, DAXX, PAX5, Runx2,
      associated with GAD67 regulation. Overall, these results suggest that the HiB5
      cells can differentiate into functionally mature GABA neurons in the presence of
      gene products that are associated with GAD67 regulation in the adult hippocampus.

PMID- 22457756
TI  - Learning about the functions of the olfactory system from people without a sense
      of smell.
AB  - The olfactory system provides numerous functions to humans, influencing ingestive
      behavior, awareness of environmental hazards and social communication.
      Approximately 1/5 of the general population exhibit an impaired sense of smell.
      However, in contrast to the many affected, only few patients complain of their
      impairment. So how important is it for humans to have an intact sense of smell?
      Or is it even dispensable, at least in the Western world? To investigate this, we
      compared 32 patients, who were born without a sense of smell (isolated congenital
      anosmia--ICA) with 36 age-matched controls. A broad questionnaire was used,
      containing domains relevant to olfaction in daily life, along with a
      questionnaire about social relationships and the BDI-questionnaire. ICA-patients
      differed only slightly from controls in functions of daily life related to
      olfaction. These differences included enhanced social insecurity, increased risk
      for depressive symptoms and increased risk for household accidents. In these
      domains the sense of olfaction seems to play a key role.

PMID- 22457757
TI  - Effects of antenatal glucocorticoid therapy on hippocampal histology of preterm
      infants.
AB  - OBJECTIVE: To investigate if antenatal glucocorticoid treatment has an effect on
      hippocampal histology of the human preterm newborn. PATIENTS AND METHODS:
      Included were consecutive neonates with a gestational age between 24 and 32
      weeks, who were born between 1991 to 2009, who had died within 4 days after
      delivery and underwent brain autopsy. Excluded were neonates with congenital
      malformations and neonates treated postnatally with glucocorticoids. The brains
      were routinely fixed, samples of the hippocampus were stained with haematoxylin
      and eosin and sections were examined for presence or absence of large and small
      neurons in regions of the hippocampus. Additional staining with GFAP,
      neurofilament and vimentin was performed to evaluate gliosis and myelination. The
      proliferation marker Ki67 was used to evaluate neuronal proliferation. Staining
      with acid fuchsin-thionin was performed to evaluate ischemic damage. RESULTS: The
      hippocampi of ten neonates who had been treated with antenatal glucocorticoids
      showed a lower density of large neurons (p = 0.01) and neurons irrespective of
      size (p = 0.02) as compared to eleven neonates who had not been treated with
      glucocorticoids. No difference was found in density of small neurons, in
      myelination, gliosis, proliferation or ischemic damage. CONCLUSION: We found a
      significantly lower density of neurons in the hippocampus of neonates after
      antenatal glucocorticoid treatment. Although the pathophysiological and clinical
      interpretations of these findings are not clear, they are consistent with those
      from experiments in mice and rhesus monkeys.

PMID- 22457758
TI  - Nanostructured oxygen sensor--using micelles to incorporate a hydrophobic
      platinum porphyrin.
AB  - Hydrophobic platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)
      porphyrin (PtTFPP) was physically incorporated into micelles formed from
      poly(epsilon-caprolactone)-block-poly(ethylene glycol) to enable the application
      of PtTFPP in aqueous solution. Micelles were characterized using dynamic light
      scattering (DLS) and atomic force microscopy (AFM) to show an average diameter of
      about 140 nm. PtTFPP showed higher quantum efficiency in micellar solution than
      in tetrahydrofuran (THF) and dichloromethane (CH2Cl2). PtTFPP in micelles also
      exhibited higher photostability than that of PtTFPP suspended in water. PtTFPP in
      micelles exhibited good oxygen sensitivity and response time. This study provided
      an efficient approach to enable the application of hydrophobic oxygen sensors in
      a biological environment.

PMID- 22457759
TI  - Rapidly measuring the speed of unconscious learning: amnesics learn quickly and
      happy people slowly.
AB  - BACKGROUND: We introduce a method for quickly determining the rate of implicit
      learning. METHODOLOGY/PRINCIPAL FINDINGS: The task involves making a binary
      prediction for a probabilistic sequence over 10 minutes; from this it is possible
      to determine the influence of events of a different number of trials in the past
      on the current decision. This profile directly reflects the learning rate
      parameter of a large class of learning algorithms including the delta and
      Rescorla-Wagner rules. To illustrate the use of the method, we compare a person
      with amnesia with normal controls and we compare people with induced happy and
      sad moods. CONCLUSIONS/SIGNIFICANCE: Learning on the task is likely both
      associative and implicit. We argue theoretically and demonstrate empirically that
      both amnesia and also transient negative moods can be associated with an
      especially large learning rate: People with amnesia can learn quickly and happy
      people slowly.

PMID- 22457760
TI  - Invariant NKT cells drive hepatic cytokinic microenvironment favoring efficient
      granuloma formation and early control of Leishmania donovani infection.
AB  - The development of inflammatory granulomas around infected Kupffer cells is
      necessary for hepatic parasite clearance during visceral leishmaniasis. Invariant
      NKT (iNKT) cells are predominant T cells in the mouse liver and can synthesize
      large quantities of IL-4 and IFN-gamma, two cytokines involved in granuloma
      formation. This study analyzed the role of iNKT cells in the hepatic immune
      response during Leishmania donovani infection, using a murine model of wild-type
      (WT) and iNKT cell-deficient (Jalpha18-/-) C57BL/6 mice sacrificed 15, 30 or 60
      days post-infection. We recorded hepatic parasite loads, cytokine expression, and
      analyzed granulomatous response by immunohistochemistry and hepatic immune cell
      infiltration by flow cytometry. Whereas WT animals rapidly controlled the
      infection and developed an inflammatory response associated with a massive influx
      of iNKT cells observed by flow cytometry, Jalpha18-/- mice had significantly
      higher parasitic loads on all time points. This lack of control of parasite
      burden was associated with a delay in granuloma maturation (28.1% of large
      granulomas at day 60 versus 50.7% in WT). Cytokine transcriptome analysis showed
      that mRNA of 90/101 genes encoding chemokines, cytokines and their receptors, was
      underexpressed in Jalpha18-/- mice. Detection of IL-4 and TNF-alpha by ELISA in
      liver extracts was also significantly lower in Jalpha18-/- mice. Consistent with
      flow cytometry analysis, cytokinome profile in WT mice showed a bias of
      expression towards T cell-chemoattractant chemokines on D15, and displayed a
      switch towards expression of granulocytes and/or monocytes -chemoattractant
      chemokines on D60. In Jalpha18-/- mice, the significantly lower expression of
      CXCL5, MIP-2 and CCL2 mRNA was correlated with a defect in myeloperoxidase
      positive-cell attraction observed by immunohistochemistry and with a lower
      granulocyte and monocyte infiltration in the liver, as shown by flow cytometry.
      These data indicate that iNKT cells play a role in early and sustained pro
      inflammatory cytokine response warranting efficient organization of hepatic
      granulomas and parasite clearance.

PMID- 22457761
TI  - Activation status of Wnt/beta-catenin signaling in normal and neoplastic breast
      tissues: relationship to HER2/neu expression in human and mouse.
AB  - Wnt/beta-catenin signaling is strongly implicated in neoplasia, but the role of
      this pathway in human breast cancer has been controversial. Here, we examined
      Wnt/beta-catenin pathway activation as a function of breast cancer progression,
      and tested for a relationship with HER2/neu expression, using a human tissue
      microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS), and
      invasive carcinomas. Cores were scored for membranous beta-catenin, a key
      functional component of adherens junctions, and for nucleocytoplasmic beta
      catenin, a hallmark of Wnt/beta-catenin pathway activation. Only 82% of benign
      samples exhibited membrane-associated beta-catenin, indicating a finite frequency
      of false-negative staining. The frequency of membrane positivity was similar in
      DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001),
      consistent with loss of adherens junctions during acquisition of invasiveness.
      Negative membrane status in cancers correlated with higher grade (P = 0.04) and
      estrogen receptor-negative status (P = 0.03), both indices of poor prognosis.
      Unexpectedly, a substantial frequency of nucleocytoplasmic beta-catenin was
      observed in benign breast tissues (36%), similar to that in carcinomas (35%).
      Positive-staining basal nuclei observed in benign breast may identify putative
      stem cells. An increased frequency of nucleocytoplasmic beta-catenin was observed
      in DCIS tumors (56%), suggesting that pathway activation may be an early event in
      human breast neoplasia. A correlation was observed between HER2/neu expression
      and nucleocytoplasmic beta-catenin in node-positive carcinomas (P = 0.02).
      Furthermore, cytoplasmic beta-catenin was detected in HER2/neu-induced mouse
      mammary tumors. The Axin2(NLSlacZ) mouse strain, a previously validated reporter
      of mammary Wnt/beta-catenin signaling, was utilized to define in vivo
      transcriptional consequences of HER2/neu-induced beta-catenin accumulation.
      Discrete hyperplastic foci observed in mammary glands from bigenic MMTV/neu,
      Axin2(NLSlacZ) mice, highlighted by robust beta-catenin/TCF signaling, likely
      represent the earliest stage of mammary intraepithelial neoplasia in MMTV/neu
      mice. Our study thus provides provocative evidence for Wnt/beta-catenin signaling
      as an early, HER2/neu-inducible event in breast neoplasia.

PMID- 22457762
TI  - Vitamin D levels in asymptomatic adults--a population survey in Karachi,
      Pakistan.
AB  - BACKGROUND: It is well established that low levels of 25(OH) Vitamin D (<30
      ng/dL) are a common finding world over, affecting over a billion of the global
      population. Our primary objective was to determine the prevalence of vitamin D
      deficiency and insufficiency in the asymptomatic adult population of Karachi,
      Pakistan and the demographic, nutritional and co-morbidity characteristics
      associated with serum vitamin D levels. METHODS: A cross-sectional population
      survey was conducted at two spaced out densely populated areas of the city. Serum
      levels of 25OH vitamin D were measured and GFR as renal function was assessed by
      using 4 variable MDRD formula. RESULTS: Our sample of 300 had a median age of
      48(interquartile range 38-55) years. The median level of serum vitamin D was 18.8
      (IQ range 12.65-24.62) ng/dL. A total of 253 (84.3%) respondents had low levels
      (<30 ng/dL) of 25OH vitamin D. Serum PTH and vitamin D were negatively correlated
      (r = -0.176, p = 0.001). The median PTH in the vitamin D sufficiency group was
      38.4 (IQ range28.0-48.8)pg/mL compared with 44.4 (IQ range 34.3-56.8) pg/mL in
      the deficiency group (p = 0.011).The median serum calcium level in the sample was
      9.46(IQ range 9.18-9.68) ng/dL. Low serum levels of vitamin D were not associated
      with hypertension (p = 0.771) or with an elevated spot blood pressure (p =
      0.164).In our sample 75(26%) respondents had an eGFR corresponding to stage 2 and
      stage 3 CKD. There was no significant correlation between levels of vitamin D and
      eGFR (r = -0.127, p-value = 0.277). Respondents using daily vitamin D supplements
      had higher 25 OH vitamin D levels (p-value = 0.021). CONCLUSION: We observed a
      high proportion of the asymptomatic adult population having low levels of vitamin
      D and subclinical deterioration of eGFR. The specific cause(s) for this observed
      high prevalence of low 25OH vitamin D levels are not clear and need to be
      investigated further upon.

PMID- 22457763
TI  - Inhibitory activity of bevacizumab to differentiation of retinoblastoma cells.
AB  - Vascular endothelial growth factor (VEGF) is a major regulator in retinal and
      choroidal angiogenesis, which are common causes of blindness in all age groups.
      Recently anti-VEGF treatment using anti-VEGF antibody has revolutionarily
      improved the visual outcome in patients with vaso-proliferative retinopathies.
      Herein, we demonstrated that bevacizumab as an anti-VEGF antibody could inhibit
      differentiation of retinoblastoma cells without affection to cellular viability,
      which would be mediated via blockade of extracellular signal-regulated kinase
      (ERK) 1/2 activation. The retinoblastoma cells expressed VEGFR-2 as well as TrkA
      which is a neurotrophin receptor associated with differentiation of
      retinoblastoma cells. TrkA in retinoblastoma cells was activated with VEGF
      treatment. Interestingly even in the concentration of no cellular death,
      bevascizumab significantly attenuated the neurite formation of differentiated
      retinoblastoma cells, which was accompanied by inhibition of neurofilament and
      shank2 expression. Furthermore, bevacizumab inhibited differentiation of
      retinoblastoma cells by blockade of ERK 1/2 activation. Therefore, based on that
      the differentiated retinoblastoma cells are mostly photoreceptors, our results
      suggest that anti-VEGF therapies would affect to the maintenance or function of
      photoreceptors in mature retina.

PMID- 22457764
TI  - Functional gene-expression analysis shows involvement of schizophrenia-relevant
      pathways in patients with 22q11 deletion syndrome.
AB  - 22q11 Deletion Syndrome (22q11DS) is associated with dysmorphology and a high
      prevalence of schizophrenia-like symptoms. Several genes located on chromosome
      22q11 have been linked to schizophrenia. The deletion is thought to disrupt the
      expression of multiple genes involved in maturation and development of neurons
      and neuronal circuits, and neurotransmission. We investigated whole-genome gene
      expression of Peripheral Blood Mononuclear Cells (PBMC's) of 8 22q11DS patients
      and 8 age- and gender-matched controls, to (1) investigate the expression levels
      of 22q11 genes and (2) to investigate whether 22q11 genes participate in
      functional genetic networks relevant to schizophrenia. Functional relationships
      between genes differentially expressed in patients (as identified by Locally
      Adaptive Statistical procedure (LAP) or satisfying p<0.05 and fold-change >1.5)
      were investigated with the Ingenuity Pathways Analysis (IPA). 14 samples (7
      patients, 7 controls) passed quality controls. LAP identified 29 deregulated
      genes. Pathway analysis showed 262 transcripts differentially expressed between
      patients and controls. Functional pathways most disturbed were cell death, cell
      morphology, cellular assembly and organization, and cell-to-cell signaling. In
      addition, 10 canonical pathways were identified, among which the signal pathways
      for Natural Killer-cells, neurotrophin/Trk, neuregulin, axonal guidance, and
      Huntington's disease. Our findings support the use of 22q11DS as a research model
      for schizophrenia. We identified decreased expression of several genes (among
      which COMT, Ufd1L, PCQAP, and GNB1L) previously linked to schizophrenia as well
      as involvement of signaling pathways relevant to schizophrenia, of which
      Neurotrophin/Trk and neuregulin signaling seems to be especially notable.

PMID- 22457765
TI  - Prevalence of hepatitis e virus in swine fed on kitchen residue.
AB  - The aim of this study was to investigate the prevalence of swine hepatitis E
      virus (HEV) in pigs fed different feedstuffs (kitchen residue or mixed feeds) and
      genetic identification of HEV isolated in Hebei province, China. Serum and fecal
      samples were collected from adult swine. Anti-HEV antibody was evaluated by
      double sandwich antigen enzyme immunoassay. HEV RNA was extracted from fecal
      samples and amplified by nested RT-PCR. The reaction products were sequenced, and
      the sequence analyzed. Virus-like particles were distinguishable by negative
      staining in the electron microscope. Histopathological observation and
      immunohistochemical localization were used in the animal models. Overall, the
      anti-HEV positive percentage of serum samples from pigs fed on kitchen residue
      was 87.10% (27/31), and 53.06% (130/245) from pigs fed on complete feed. The HEV
      RNA positivity rate of fecal samples from pigs fed on kitchen residue was 61.54%
      (8/13), but zero for pigs fed on complete feed. Sequence analysis of these eight
      samples and comparison with the published sequence showed that there were eight
      groups that belonged to genotype 4 d and the nucleotide identity was 95.6-99.3%.
      swHE11 is most closely related to strain CCC220, and the other seven HEV isolates
      were most closely related to strains swGX40, SwCH189 and V0008ORF3, which are
      isolates from human and pigs. Histopathological observation showed that there was
      liver damage in the experimental group, and immunohistochemistry indicated that
      the HEV antigens were strongly positive at 7 days after infection. The results
      demonstrated that the prevalence of HEV in pigs fed on kitchen residue was higher
      than in those fed on complete feed (P<0.05).

PMID- 22457766
TI  - WormScan: a technique for high-throughput phenotypic analysis of Caenorhabditis
      elegans.
AB  - BACKGROUND: There are four main phenotypes that are assessed in whole organism
      studies of Caenorhabditis elegans; mortality, movement, fecundity and size.
      Procedures have been developed that focus on the digital analysis of some, but
      not all of these phenotypes and may be limited by expense and limited throughput.
      We have developed WormScan, an automated image acquisition system that allows
      quantitative analysis of each of these four phenotypes on standard NGM plates
      seeded with E. coli. This system is very easy to implement and has the capacity
      to be used in high-throughput analysis. METHODOLOGY/PRINCIPAL FINDINGS: Our
      system employs a readily available consumer grade flatbed scanner. The method
      uses light stimulus from the scanner rather than physical stimulus to induce
      movement. With two sequential scans it is possible to quantify the induced
      phototactic response. To demonstrate the utility of the method, we measured the
      phenotypic response of C. elegans to phosphine gas exposure. We found that
      stimulation of movement by the light of the scanner was equivalent to physical
      stimulation for the determination of mortality. WormScan also provided a
      quantitative assessment of health for the survivors. Habituation from light
      stimulation of continuous scans was similar to habituation caused by physical
      stimulus. CONCLUSIONS/SIGNIFICANCE: There are existing systems for the automated
      phenotypic data collection of C. elegans. The specific advantages of our method
      over existing systems are high-throughput assessment of a greater range of
      phenotypic endpoints including determination of mortality and quantification of
      the mobility of survivors. Our system is also inexpensive and very easy to
      implement. Even though we have focused on demonstrating the usefulness of
      WormScan in toxicology, it can be used in a wide range of additional C. elegans
      studies including lifespan determination, development, pathology and behavior.
      Moreover, we have even adapted the method to study other species of similar
      dimensions.

PMID- 22457767
TI  - Hepatitis B vaccine antibody response and the risk of clinical AIDS or death.
AB  - BACKGROUND: Whether seroresponse to a vaccine such as hepatitis B virus (HBV)
      vaccine can provide a measure of the functional immune status of HIV-infected
      persons is unknown.This study evaluated the relationship between HBV vaccine
      seroresponses and progression to clinical AIDS or death. METHODS AND FINDINGS:
      From a large HIV cohort, we evaluated those who received HBV vaccine only after
      HIV diagnosis and had anti-HBs determination 1-12 months after the last vaccine
      dose. Non-response and positive response were defined as anti-HBs <10 and >= 10
      IU/L, respectively. Participants were followed from date of last vaccination to
      clinical AIDS, death, or last visit. Univariate and multivariable risk of
      progression to clinical AIDS or death were evaluated with Cox regression models.
      A total of 795 participants vaccinated from 1986-2010 were included, of which 41%
      were responders. During 3,872 person-years of observation, 122 AIDS or death
      events occurred (53% after 1995). Twenty-two percent of non-responders
      experienced clinical AIDS or death compared with 5% of responders (p<0.001). Non
      response to HBV vaccine was associated with a greater than 2-fold increased risk
      of clinical AIDS or death (HR 2.47; 95% CI, 1.38-4.43) compared with a positive
      response, after adjusting for CD4 count, HIV viral load, HAART use, and delayed
      type hypersensitivity skin test responses (an in vivo marker of cell-mediated
      immunity). This association remained evident among those with CD4 count >= 500
      cells/mm3 (HR 3.40; 95% CI, 1.39-8.32). CONCLUSIONS: HBV vaccine responses may
      have utility in assessing functional immune status and risk stratificating HIV
      infected individuals, including those with CD4 count >= 500 cells/mm3.

PMID- 22457768
TI  - A preliminary evaluation of limb salvage surgery for osteosarcoma around knee
      joint.
AB  - OBJECTIVE: To evaluate the effectiveness and drawbacks of diversified procedures
      of limb salvage surgery (LSS), providing a reference of rational surgical
      criterion of LSS. METHODS: Fifty eight patients with stage IIB extremity
      osteosarcoma around knee joint area between 1992 and 2002 were studied
      retrospectively. Among them, 43 patients were treated by LSS followed by
      reconstruction. Reconstruction approaches included re-implantation of irradiation
      devitalized tumor bone (n = 12), autoclaving-devitalized tumor bone (n = 8),
      prosthetic replacement (n = 11), allograft transplantation (n = 8) and
      vascularized fibula autograft implantation (n = 4). Amputations were performed in
      15 patients. Patients were followed up for 6-16 years. RESULTS: There were no
      significant difference between LSS and amputation groups regarding disease free
      survival and local recurrence rates. The actuarial 5-year continuous disease free
      survival and local recurrence rate were 30.0% and 25.0% in patients of
      devitalized LSS group, whereas those were 56.5% and 8.7% in patients of non
      devitalized reconstruction group. The complication rate was significantly higher
      in LSS group compared to amputation group (P = 0.003). CONCLUSION: LSS with non
      devitalized procedures is the optimal treatment for osteosarcoma around knee
      joint area. Prosthesis implantation is the preferred option for bone
      reconstruction following LSS. Prevention and treatment of post-operative
      complications should be paid more attention to get good long-term outcomes of
      surgery.

PMID- 22457769
TI  - Daf-2 signaling modifies mutant SOD1 toxicity in C. elegans.
AB  - The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of
      Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk
      factor for developing neurodegenerative diseases such as Amyotrophic Lateral
      Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies
      disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans.
      Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired
      locomotion as compared to WT SOD1 expressing controls and they develop insoluble
      SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic
      allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1
      and results in improved locomotion in a DAF-16 dependant manner. These results
      suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have
      therapeutic potential for the treatment of ALS.

PMID- 22457770
TI  - Increased expression and altered methylation of HERVWE1 in the human placentas of
      smaller fetuses from monozygotic, dichorionic, discordant twins.
AB  - BACKGROUND: The human endogenous retroviral family W, Env(C7), member 1 gene
      (HERVWE1) is thought to participate in trophoblast cell fusion, and its
      expression is diminished in the placentas of singleton intrauterine growth
      retarded pregnancies. However, there is limited information about the role of
      HERVWE1 in discordant fetal growth in twins. This study was to compare HERVWE1
      gene expression between the placentas of discordant monozygotic twins and to
      identify its regulation by methylation. METHODOLOGY/PRINCIPAL FINDINGS: Fetuses
      from twenty-one pairs of monozygotic, dichorionic, discordant twins were marked
      as "smaller" or "larger" according to birth weight. Placental HERVWE1 mRNA and
      protein expression profiles were analyzed using quantitative RT-PCR and
      immunohistochemistry (IHC) staining. Methylation profiles of the HERVWE1 promoter
      region were analyzed using a pyrosequencing assay. DNA methyltransferase (DNMT)
      transcript levels were analyzed by RT-PCR. 5-methyl cytosine (5-MC) was stained
      using an immunohistochemical assay. There was a significant negative correlation
      between HERVWE1 mRNA levels and birth weight in twins (P<0.01). Whereas the mean
      methylation level of the HERVWE1 promoter region was diminished in the smaller
      group in discordant twins(P<0.01), increased mRNA and protein levels of HERVWE1
      were found in smaller fetuses compared with larger fetuses in discordant
      twins(P<0.01). There was no significant difference in 5-MC staining intensity
      between discordant twins (P>0.05). The DNMT3b3 mRNA levels in the smaller group
      were significantly downregulated compared with the larger group in discordant
      twins(P<0.05), whereas the DNMT3b7 mRNA levels in the smaller group were
      significantly upregulated compared with the larger group in discordant
      twins(P<0.05). CONCLUSIONS/SIGNIFICANCE: In discordant, monozygotic, dichorionic
      twins, HERVWE1 expression was higher in smaller fetuses and lower in larger
      fetuses. Methylation of the HERVWE1 gene promoter region may participate in the
      regulation of HERVWE1 gene expression in discordant twin pregnancies.

PMID- 22457771
TI  - Blueberry husks and probiotics attenuate colorectal inflammation and oncogenesis,
      and liver injuries in rats exposed to cycling DSS-treatment.
AB  - Long-term colonic inflammation promotes carcinogenesis and histological
      abnormalities of the liver, and colorectal tumours frequently arise in a
      background of dysplasia, a precursor of adenomas. Altered colonic microbiota with
      an increased proportion of bacteria with pro-inflammatory characteristics, have
      been implicated in neoplastic progression. The composition of the microbiota can
      be modified by dietary components such as probiotics, polyphenols and dietary
      fibres. In the present study, the influence of probiotics in combination with
      blueberry husks on colorectal carcinogenesis and subsequent liver damage was
      evaluated.Colorectal tumours were induced in rats by cyclic treatment with
      dextran sulphate sodium (DSS). Blueberry husks and a mixture of three probiotic
      strains (Bifidobacterium infantis DSM 15159, Lactobacillus gasseri, DSM 16737 and
      Lactobacillus plantarum DSM 15313) supplemented a basic diet fortified with oats.
      The condition of the rats was monitored using a disease activity index (DAI). A
      qualitative and quantitative histological judgement was performed on segments of
      distal colon and rectum and the caudate lobe of the liver. The formation of short
      chain fatty acids, bacterial translocation, the inflammatory reaction and viable
      count of lactobacilli and Enterobaceriaceae were addressed.Blueberry husks with
      or without probiotics significantly decreased DAI, and significantly reduced the
      number of colonic ulcers and dysplastic lesions. With a decreased proportion of
      blueberry husk in the diet, the probiotic supplement was needed to achieve a
      significant decrease in numbers of dysplastic lesions. Probiotics decreased
      faecal viable count of Enterobacteriaceae and increased that of lactobacilli.
      Blueberry husks with or without probiotics lowered the proportion of butyric acid
      in distal colon, and decreased the haptoglobin levels. Probiotics mitigated
      hepatic injuries by decreasing parenchymal infiltration and the incidence of
      stasis and translocation. The results demonstrate a dietary option for use of
      blueberry husks and probiotics to delay colonic carcinogenesis and hepatic
      injuries in the rat model.

PMID- 22457772
TI  - An excitable cortex and memory model successfully predicts new pseudopod
      dynamics.
AB  - Motile eukaryotic cells migrate with directional persistence by alternating left
      and right turns, even in the absence of external cues. For example, Dictyostelium
      discoideum cells crawl by extending distinct pseudopods in an alternating right
      left pattern. The mechanisms underlying this zig-zag behavior, however, remain
      unknown. Here we propose a new Excitable Cortex and Memory (EC&M) model for
      understanding the alternating, zig-zag extension of pseudopods. Incorporating
      elements of previous models, we consider the cell cortex as an excitable system
      and include global inhibition of new pseudopods while a pseudopod is active. With
      the novel hypothesis that pseudopod activity makes the local cortex temporarily
      more excitable--thus creating a memory of previous pseudopod locations--the model
      reproduces experimentally observed zig-zag behavior. Furthermore, the EC&M model
      makes four new predictions concerning pseudopod dynamics. To test these
      predictions we develop an algorithm that detects pseudopods via hierarchical
      clustering of individual membrane extensions. Data from cell-tracking experiments
      agrees with all four predictions of the model, revealing that pseudopod placement
      is a non-Markovian process affected by the dynamics of previous pseudopods. The
      model is also compatible with known limits of chemotactic sensitivity. In
      addition to providing a predictive approach to studying eukaryotic cell motion,
      the EC&M model provides a general framework for future models, and suggests
      directions for new research regarding the molecular mechanisms underlying
      directional persistence.

PMID- 22457773
TI  - Site-specific and time-dependent activation of the endocannabinoid system after
      transection of long-range projections.
AB  - BACKGROUND: After focal neuronal injury the endocannabinioid system becomes
      activated and protects or harms neurons depending on cannabinoid derivates and
      receptor subtypes. Endocannabinoids (eCBs) play a central role in controlling
      local responses and influencing neural plasticity and survival. However, little
      is known about the functional relevance of eCBs in long-range projection damage
      as observed in stroke or spinal cord injury (SCI). METHODS: In rat organotypic
      entorhino-hippocampal slice cultures (OHSC) as a relevant and suitable model for
      investigating projection fibers in the CNS we performed perforant pathway
      transection (PPT) and subsequently analyzed the spatial and temporal dynamics of
      eCB levels. This approach allows proper distinction of responses in originating
      neurons (entorhinal cortex), areas of deafferentiation/anterograde axonal
      degeneration (dentate gyrus) and putative changes in more distant but
      synaptically connected subfields (cornu ammonis (CA) 1 region). RESULTS: Using LC
      MS/MS, we measured a strong increase in arachidonoylethanolamide (AEA),
      oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) levels in the
      denervation zone (dentate gyrus) 24 hours post lesion (hpl), whereas entorhinal
      cortex and CA1 region exhibited little if any changes. NAPE-PLD, responsible for
      biosynthesis of eCBs, was increased early, whereas FAAH, a catabolizing enzyme,
      was up-regulated 48hpl. CONCLUSION: Neuronal damage as assessed by transection of
      long-range projections apparently provides a strong time-dependent and area
      confined signal for de novo synthesis of eCB, presumably to restrict neuronal
      damage. The present data underlines the importance of activation of the eCB
      system in CNS pathologies and identifies a novel site-specific intrinsic
      regulation of eCBs after long-range projection damage.

PMID- 22457774
TI  - Disrupted small-world brain networks in moderate Alzheimer's disease: a resting
      state FMRI study.
AB  - The small-world organization has been hypothesized to reflect a balance between
      local processing and global integration in the human brain. Previous multimodal
      imaging studies have consistently demonstrated that the topological architecture
      of the brain network is disrupted in Alzheimer's disease (AD). However, these
      studies have reported inconsistent results regarding the topological properties
      of brain alterations in AD. One potential explanation for these inconsistent
      results lies with the diverse homogeneity and distinct progressive stages of the
      AD involved in these studies, which are thought to be critical factors that might
      affect the results. We investigated the topological properties of brain
      functional networks derived from resting functional magnetic resonance imaging
      (fMRI) of carefully selected moderate AD patients and normal controls (NCs). Our
      results showed that the topological properties were found to be disrupted in AD
      patients, which showing increased local efficiency but decreased global
      efficiency. We found that the altered brain regions are mainly located in the
      default mode network, the temporal lobe and certain subcortical regions that are
      closely associated with the neuropathological changes in AD. Of note, our
      exploratory study revealed that the ApoE genotype modulates brain network
      properties, especially in AD patients.

PMID- 22457775
TI  - Identification of a novel idiopathic epilepsy locus in Belgian Shepherd dogs.
AB  - Epilepsy is the most common neurological disorder in dogs, with an incidence
      ranging from 0.5% to up to 20% in particular breeds. Canine epilepsy can be
      etiologically defined as idiopathic or symptomatic. Epileptic seizures may be
      classified as focal with or without secondary generalization, or as primary
      generalized. Nine genes have been identified for symptomatic (storage diseases)
      and one for idiopathic epilepsy in different breeds. However, the genetic
      background of common canine epilepsies remains unknown. We have studied the
      clinical and genetic background of epilepsy in Belgian Shepherds. We collected
      159 cases and 148 controls and confirmed the presence of epilepsy through
      epilepsy questionnaires and clinical examinations. The MRI was normal while
      interictal EEG revealed abnormalities and variable foci in the clinically
      examined affected dogs. A genome-wide association study using Affymetrix 50K SNP
      arrays in 40 cases and 44 controls mapped the epilepsy locus on CFA37, which was
      replicated in an independent cohort (81 cases and 88 controls; combined p =
      9.70*10-10, OR = 3.3). Fine mapping study defined a ~1 Mb region including 12
      genes of which none are known epilepsy genes or encode ion channels. Exonic
      sequencing was performed for two candidate genes, KLF7 and ADAM23. No variation
      was found in KLF7 but a highly-associated non-synonymous variant, G1203A (R387H)
      was present in the ADAM23 gene (p = 3.7*10-8, OR = 3.9 for homozygosity).
      Homozygosity for a two-SNP haplotype within the ADAM23 gene conferred the highest
      risk for epilepsy (p = 6.28*10-11, OR = 7.4). ADAM23 interacts with known
      epilepsy proteins LGI1 and LGI2. However, our data suggests that the ADAM23
      variant is a polymorphism and we have initiated a targeted re-sequencing study
      across the locus to identify the causative mutation. It would establish the
      affected breed as a novel therapeutic model, help to develop a DNA test for
      breeding purposes and introduce a novel candidate gene for human idiopathic
      epilepsies.

PMID- 22457776
TI  - The zinc dyshomeostasis hypothesis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia in the elderly.
      Hallmark AD neuropathology includes extracellular amyloid plaques composed
      largely of the amyloid-beta protein (Abeta), intracellular neurofibrillary
      tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein
      tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD
      genes are associated with excessive Abeta accumulation, however cognitive
      impairment best correlates with NFTs and disrupted microtubules. The mechanisms
      linking Abeta and NFT pathologies in AD are unknown. Here, we propose that
      sequestration of zinc by Abeta-amyloid deposits (Abeta oligomers and plaques) not
      only drives Abeta aggregation, but also disrupts zinc homeostasis in zinc
      enriched brain regions important for memory and vulnerable to AD pathology,
      resulting in intra-neuronal zinc levels, which are either too low, or excessively
      high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding
      to the microtubule component protein tubulin, identifying specific, high-affinity
      zinc binding sites that influence side-to-side tubulin interaction, the sensitive
      link in microtubule polymerization and stability. We also 2) performed kinetic
      modeling showing zinc distribution in extra-neuronal Abeta deposits can reduce
      intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally,
      we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically
      localized and age-dependent zinc dyshomeostasis in specific brain regions of
      Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions
      associated with memory processing and NFT pathology. Overall, we present a
      theoretical framework and support for a new theory of AD linking extra-neuronal
      Abeta amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection,
      we propose, is based on beta-amyloid-induced alterations in zinc ion
      concentration inside neurons affecting stability of polymerized microtubules,
      their binding to MAP-tau, and molecular dynamics involved in cognition. Further,
      our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc
      homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive
      decline.

PMID- 22457777
TI  - Molecular characterisation of transport mechanisms at the developing mouse blood
      CSF interface: a transcriptome approach.
AB  - Exchange mechanisms across the blood-cerebrospinal fluid (CSF) barrier in the
      choroid plexuses within the cerebral ventricles control access of molecules to
      the central nervous system, especially in early development when the brain is
      poorly vascularised. However, little is known about their molecular or
      developmental characteristics. We examined the transcriptome of lateral
      ventricular choroid plexus in embryonic day 15 (E15) and adult mice. Numerous
      genes identified in the adult were expressed at similar levels at E15, indicating
      substantial plexus maturity early in development. Some genes coding for key
      functions (intercellular/tight junctions, influx/efflux transporters) changed
      expression during development and their expression patterns are discussed in the
      context of available physiological/permeability results in the developing brain.
      Three genes: Secreted protein acidic and rich in cysteine (Sparc), Glycophorin A
      (Gypa) and C (Gypc), were identified as those whose gene products are candidates
      to target plasma proteins to choroid plexus cells. These were investigated using
      quantitative- and single-cell-PCR on plexus epithelial cells that were albumin-
      or total plasma protein-immunopositive. Results showed a significant degree of
      concordance between plasma protein/albumin immunoreactivity and expression of the
      putative transporters. Immunohistochemistry identified SPARC and GYPA in choroid
      plexus epithelial cells in the embryo with a subcellular distribution that was
      consistent with transport of albumin from blood to cerebrospinal fluid. In adult
      plexus this pattern of immunostaining was absent. We propose a model of the
      cellular mechanism in which SPARC and GYPA, together with identified vesicle
      associated membrane proteins (VAMPs) may act as receptors/transporters in
      developmentally regulated transfer of plasma proteins at the blood-CSF interface.

PMID- 22457778
TI  - Characterization of a FGF19 variant with altered receptor specificity revealed a
      central role for FGFR1c in the regulation of glucose metabolism.
AB  - Diabetes and associated metabolic conditions have reached pandemic proportions
      worldwide, and there is a clear unmet medical need for new therapies that are
      both effective and safe. FGF19 and FGF21 are distinctive members of the FGF
      family that function as endocrine hormones. Both have potent effects on
      normalizing glucose, lipid, and energy homeostasis, and therefore, represent
      attractive potential next generation therapies for combating the growing
      epidemics of type 2 diabetes and obesity. The mechanism responsible for these
      impressive metabolic effects remains unknown. While both FGF19 and FGF21 can
      activate FGFRs 1c, 2c, and 3c in the presence of co-receptor betaKlotho in vitro,
      which receptor is responsible for the metabolic activities observed in vivo
      remains unknown. Here we have generated a variant of FGF19, FGF19-7, that has
      altered receptor specificity with a strong bias toward FGFR1c. We show that FGF19
      7 is equally efficacious as wild type FGF19 in regulating glucose, lipid, and
      energy metabolism in both diet-induced obesity and leptin-deficient mouse models.
      These results are the first direct demonstration of the central role of the
      betaKlotho/FGFR1c receptor complex in glucose and lipid regulation, and also
      strongly suggest that activation of this receptor complex alone might be
      sufficient to achieve all the metabolic functions of endocrine FGF molecules.

PMID- 22457779
TI  - How morphological constraints affect axonal polarity in mouse neurons.
AB  - Neuronal differentiation is under the tight control of both biochemical and
      physical information arising from neighboring cells and micro-environment. Here
      we wished to assay how external geometrical constraints applied to the cell body
      and/or the neurites of hippocampal neurons may modulate axonal polarization in
      vitro. Through the use of a panel of non-specific poly-L-lysine micropatterns, we
      manipulated the neuronal shape. By applying geometrical constraints on the cell
      body we provided evidence that centrosome location was not predictive of axonal
      polarization but rather follows axonal fate. When the geometrical constraints
      were applied to the neurites trajectories we demonstrated that axonal
      specification was inhibited by curved lines. Altogether these results indicated
      that intrinsic mechanical tensions occur during neuritic growth and that maximal
      tension was developed by the axon and expressed on straight trajectories. The
      strong inhibitory effect of curved lines on axon specification was further
      demonstrated by their ability to prevent formation of multiple axons normally
      induced by cytochalasin or taxol treatments. Finally we provided evidence that
      microtubules were involved in the tension-mediated axonal polarization, acting as
      curvature sensors during neuronal differentiation. Thus, biomechanics coupled to
      physical constraints might be the first level of regulation during neuronal
      development, primary to biochemical and guidance regulations.

PMID- 22457780
TI  - Ligation of the jugular veins does not result in brain inflammation or
      demyelination in mice.
AB  - An alternative hypothesis has been proposed implicating chronic cerebrospinal
      venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We
      aimed to evaluate the validity of this hypothesis in a controlled animal model.
      Animal experiments were approved by the institutional animal care committee. The
      jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were
      observed for up to six months after ligation. Sham-operated mice (n = 15) and
      mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as
      negative and positive controls, respectively. The animals were evaluated using CT
      venography and (99m)Tc-exametazime to assess for structural and hemodynamic
      changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB)
      breakdown and neuroinflammation. Flow cytometry and histopathology were performed
      to assess inflammatory cell populations and demyelination. There were both
      structural changes (stenosis, collaterals) in the jugular venous drainage and
      hemodynamic disturbances in the brain on Tc99m-exametazime scintigraphy (p =
      0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for
      barrier molecules did not reveal evidence of BBB breakdown (p = 0.58).
      Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not
      reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and
      histopathology also did not reveal increase in inflammatory cell infiltration or
      population shifts. No evidence of demyelination was found, and the mice remained
      without clinical signs. Despite the structural and hemodynamic changes, we did
      not identify changes in the BBB permeability, neuroinflammation, demyelination,
      or clinical signs in the JVL group compared to the sham group. Therefore, our
      murine model does not support CCSVI as a cause of demyelinating diseases such as
      multiple sclerosis.

PMID- 22457781
TI  - PTPN2 gene variants are associated with susceptibility to both Crohn's disease
      and ulcerative colitis supporting a common genetic disease background.
AB  - BACKGROUND: Genome-wide association studies identified PTPN2 (protein tyrosine
      phosphatase, non-receptor type 2) as susceptibility gene for inflammatory bowel
      diseases (IBD). However, the exact role of PTPN2 in Crohn's disease (CD) and
      ulcerative colitis (UC) and its phenotypic effect are unclear. We therefore
      performed a detailed genotype-phenotype and epistasis analysis of PTPN2 gene
      variants. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 2131 individuals of
      Caucasian origin (905 patients with CD, 318 patients with UC, and 908 healthy,
      unrelated controls) was analyzed for two SNPs in the PTPN2 region (rs2542151,
      rs7234029) for which associations with IBD were found in previous studies in
      other cohorts. Our analysis revealed a significant association of PTPN2 SNP
      rs2542151 with both susceptibility to CD (p = 1.95*10-5; OR 1.49 [1.34-1.79]) and
      UC (p = 3.87*10-2, OR 1.31 [1.02-1.68]). Moreover, PTPN2 SNP rs7234029
      demonstrated a significant association with susceptibility to CD (p = 1.30*10-3;
      OR 1.35 [1.13-1.62]) and a trend towards association with UC (p = 7.53*10-2; OR
      1.26 [0.98-1.62]). Genotype-phenotype analysis revealed an association of PTPN2
      SNP rs7234029 with a stricturing disease phenotype (B2) in CD patients (p =
      6.62*10-3). Epistasis analysis showed weak epistasis between the ATG16L1 SNP
      rs2241879 and PTPN2 SNP rs2542151 (p = 0.024) in CD and between ATG16L1 SNP
      rs4663396 and PTPN2 SNP rs7234029 (p = 4.68*10-3) in UC. There was no evidence of
      epistasis between PTPN2 and NOD2 and PTPN2 and IL23R. In silico analysis revealed
      that the SNP rs7234029 modulates potentially the binding sites of several
      transcription factors involved in inflammation including GATA-3, NF-kappaB,
      C/EBP, and E4BP4. CONCLUSIONS/SIGNIFICANCE: Our data confirm the association of
      PTPN2 variants with susceptibility to both CD and UC, suggesting a common disease
      pathomechanism for these diseases. Given recent evidence that PTPN2 regulates
      autophagosome formation in intestinal epithelial cells, the potential link
      between PTPN2 and ATG16L1 should be further investigated.

PMID- 22457782
TI  - HIV status disclosure and retention in care in HIV-infected adolescents on
      antiretroviral therapy (ART) in West Africa.
AB  - OBJECTIVE: We assessed the effect of HIV status disclosure on retention in care
      from initiation of antiretroviral therapy (ART) among HIV-infected children aged
      10 years or more in Cote d'Ivoire, Mali and Senegal. METHODS: Multi-centre cohort
      study within five paediatric clinics participating in the IeDEA West Africa
      collaboration. HIV-infected patients were included in this study if they met the
      following inclusion criteria: aged 10-21 years while on ART; having initiated ART
      >= 200 days before the closure date of the clinic database; followed >= 15 days
      from ART initiation in clinics with >= 10 adolescents enrolled. Routine follow-up
      data were merged with those collected through a standardized ad hoc questionnaire
      on awareness of HIV status. Probability of retention (no death or loss-to-follow
      up) was estimated with Kaplan-Meier method. Cox proportional hazard model with
      date of ART initiation as origin and a delayed entry at date of 10th birthday was
      used to identify factors associated with death or loss-to-follow-up. RESULTS: 650
      adolescents were available for this analysis. Characteristics at ART initiation
      were: median age of 10.4 years; median CD4 count of 224 cells/mm3 (47% with
      severe immunosuppression), 48% CDC stage C/WHO stage 3/4. The median follow-up on
      ART after the age of 10 was 23.3 months; 187 adolescents (28.8%) knew their HIV
      status. The overall probability of retention at 36 months after ART initiation
      was 74.6% (95% confidence interval [CI]: 70.5-79.0) and was higher for those
      disclosed compared to those not: adjusted hazard ratio for the risk of being
      death or loss-to-follow-up = 0.23 (95% CI: 0.13-0.39). CONCLUSION: About 2/3 of
      HIV-infected adolescents on ART were not aware of their HIV status in these ART
      clinics in West Africa but disclosed HIV status improved retention in care. The
      disclosure process should be thus systematically encouraged and organized in
      adolescent populations.

PMID- 22457784
TI  - Computable features required to evaluate the efficacy of drugs and a universal
      algorithm to find optimally effective drug in a drug complex.
AB  - BACKGROUND: The H1N1 pandemic in 2009 and the H5N1 pandemic in 2005 demonstrated
      that the drugs approved to treat influenza A viruses have low efficacy. This
      provided a stimulus for new studies of influenza A viruses in the context of the
      methods used in drug design developed over the past 100 years. Finding new
      universal drugs is the ultimate goal but its long time horizon is incompatible
      with emergency situations created by reoccurring influenza outbreaks. Therefore,
      we propose a computer-aided method for finding efficacious drugs and drug
      complexes based on the use of the DrugBank database. METHODS: (1) We start by
      assembling a panel of target proteins. (2) We then assemble a panel of drugs. (3)
      This is followed by a selection of benchmark binding pockets based on the panel
      of target proteins and the panel of drugs. (4) We generate a set of computational
      features, which measure the efficacy of a drug. (5) We propose a universal
      program to search for drugs and drug complexes. (6) A case study we report here
      illustrates how to use this universal program for finding an optimal drug and a
      drug complex for a given target. (7) Validation of the Azirchromycin and Aspirin
      complex is provided mathematically. (8) Finally, we propose a simple strategy to
      validate our computational prediction that the Azirchromycin and Aspirin complex
      should prove clinically effective. RESULT: A set of computable features are mined
      and then based on these features, a universal program for finding the potential
      drug &drug complexes is proposed. Using this universal program, the Azirchromycin
      and Aspirin complex is selected and its efficacy is predicted mathematically. For
      clinical validation of this finding, future work is still required.

PMID- 22457783
TI  - Abnormal distracter processing in adults with attention-deficit-hyperactivity
      disorder.
AB  - BACKGROUND: Subjects with Attention-Deficit Hyperactivity Disorder (ADHD) are
      overdistractible by stimuli out of the intended focus of attention. This control
      deficit could be due to primarily reduced attentional capacities or, e. g., to
      overshooting orienting to unexpected events. Here, we aimed at identifying
      disease-related abnormalities of novelty processing and, therefore, studied event
      related potentials (ERP) to respective stimuli in adult ADHD patients compared to
      healthy subjects. METHODS: Fifteen unmedicated subjects with ADHD and fifteen
      matched controls engaged in a visual oddball task (OT) under simultaneous EEG
      recordings. A target stimulus, upon which a motor response was required, and non
      target stimuli, which did not demand a specific reaction, were presented in
      random order. Target and most non-target stimuli were presented repeatedly, but
      some non-target stimuli occurred only once ('novels'). These unique stimuli were
      either 'relative novels' with which a meaning could be associated, or 'complete
      novels', if no association was available. RESULTS: In frontal recordings, a
      positive component with a peak latency of some 400 ms became maximal after
      novels. In healthy subjects, this novelty-P3 (or 'orienting response') was of
      higher magnitude after complete than after relative novels, in contrast to the
      patients with an undifferentially high frontal responsivity. Instead, ADHD
      patients tended to smaller centro-parietal P3 responses after target signals and,
      on a behavioural level, responded slower than controls. CONCLUSION: The results
      demonstrate abnormal novelty processing in adult subjects with ADHD. In controls,
      the ERP pattern indicates that allocation of meaning modulates the processing of
      new stimuli. However, in ADHD such a modulation was not prevalent. Instead, also
      familiar, only context-wise new stimuli were treated as complete novels. We
      propose that disturbed semantic processing of new stimuli resembles a mechanism
      for excessive orienting to commonly negligible stimuli in ADHD.

PMID- 22457785
TI  - A fragment of the LG3 peptide of endorepellin is present in the urine of
      physically active mining workers: a potential marker of physical activity.
AB  - Biomarker analysis has been implemented in sports research in an attempt to
      monitor the effects of exertion and fatigue in athletes. This study proposed that
      while such biomarkers may be useful for monitoring injury risk in workers,
      proteomic approaches might also be utilised to identify novel exertion or injury
      markers. We found that urinary urea and cortisol levels were significantly
      elevated in mining workers following a 12 hour overnight shift. These levels
      failed to return to baseline over 24 h in the more active maintenance crew
      compared to truck drivers (operators) suggesting a lack of recovery between
      shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers
      revealed a spectral feature which was associated with workers in both work
      categories who were engaged in higher levels of physical activity. This feature
      was identified as the LG3 peptide, a C-terminal fragment of the anti
      angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that
      urinary LG3 peptide may be a biomarker of physical activity. It is also possible
      that the activity mediated release of LG3/endorepellin into the circulation may
      represent a biological mechanism for the known inverse association between
      physical activity and cancer risk/survival.

PMID- 22457786
TI  - Transient focal cerebral ischemia/reperfusion induces early and chronic axonal
      changes in rats: its importance for the risk of Alzheimer's disease.
AB  - The dementia of Alzheimer's type and brain ischemia are known to increase at
      comparable rates with age. Recent advances suggest that cerebral ischemia may
      contribute to the pathogenesis of Alzheimer's disease (AD), however, the
      neuropathological relationship between these two disorders is largely unclear. It
      has been demonstrated that axonopathy, mainly manifesting as impairment of axonal
      transport and swelling of the axon and varicosity, is a prominent feature in AD
      and may play an important role in the neuropathological mechanisms in AD. In this
      study, we investigated the early and chronic changes of the axons of neurons in
      the different brain areas (cortex, hippocampus and striatum) using in vivo
      tracing technique and grading analysis method in a rat model of transient focal
      cerebral ischemia/reperfusion (middle cerebral artery occlusion, MCAO). In
      addition, the relationship between the changes of axons and the expression of
      beta-amyloid 42 (Abeta42) and hyperphosphorylated Tau, which have been considered
      as the key neuropathological processes of AD, was analyzed by combining tracing
      technique with immunohistochemistry or western blotting. Subsequently, we found
      that transient cerebral ischemia/reperfusion produced obvious swelling of the
      axons and varicosities, from 6 hours after transient cerebral
      ischemia/reperfusion even up to 4 weeks. We could not observe Abeta plaques or
      overexpression of Abeta42 in the ischemic brain areas, however, the site-specific
      hyperphosphorylated Tau could be detected in the ischemic cortex. These results
      suggest that transient cerebral ischemia/reperfusion induce early and chronic
      axonal changes, which may be an important mechanism affecting the clinical
      outcome and possibly contributing to the development of AD after stroke.

PMID- 22457787
TI  - A new method to predict the epidemiology of fungal keratitis by monitoring the
      sales distribution of antifungal eye drops in Brazil.
AB  - PURPOSE: Fungi are a major cause of keratitis, although few medications are
      licensed for their treatment. The aim of this study is to observe the variation
      in commercialisation of antifungal eye drops, and to predict the seasonal
      distribution of fungal keratitis in Brazil. METHODS: Data from a retrospective
      study of antifungal eye drops sales from the only pharmaceutical ophthalmologic
      laboratory, authorized to dispense them in Brazil (Opthalmos) were gathered.
      These data were correlated with geographic and seasonal distribution of fungal
      keratitis in Brazil between July 2002 and June 2008. RESULTS: A total of 26,087
      antifungal eye drop units were sold, with a mean of 2.3 per patient. There was
      significant variation in antifungal sales during the year (p<0.01). A linear
      regression model displayed a significant association between reduced relative
      humidity and antifungal drug sales (R2 = 0.17,p<0.01). CONCLUSIONS: Antifungal
      eye drops sales suggest that there is a seasonal distribution of fungal
      keratitis. A possible interpretation is that the third quarter of the year (a
      period when the climate is drier), when agricultural activity is more intense in
      Brazil, suggests a correlation with a higher incidence of fungal keratitis. A
      similar model could be applied to other diseases, that are managed with unique,
      or few, and monitorable medications to predict epidemiological aspects.

PMID- 22457788
TI  - MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both
      in vitro and in vivo.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of endogenously expressed, small
      noncoding RNAs, which suppress its target mRNAs at the post-transcriptional
      level. Studies have demonstrated that miR-34a, which is a direct target of the
      p53 tumor suppressor gene, functions as a tumor suppressor and is associated with
      the tumor growth and metastasis of various human malignances. However, the role
      of miR-34a in osteosarcoma has not been totally elucidated. In the present study,
      the effects of miR-34a on osteosarcoma and the possible mechanism by which miR
      34a affected the tumor growth and metastasis of osteosarcoma were investigated.
      METHODOLOGY/PRINCIPAL FINDING: Over-expression of miR-34a partially inhibited
      proliferation, migration and invasion of osteosarcoma cells in vitro, as well as
      the tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. c-Met is
      a target of miR-34a, and regulates the migration and invasion of osteosarcoma
      cells. Osteosarcoma cells over-expressing miR-34a exhibited a significant
      decrease in the expression levels of c-Met mRNA and protein simultaneously.
      Finally, the results from bioinformatics analysis demonstrated that there were
      multiple putative targets of miR-34a that may be associated with the
      proliferation and metastasis of osteosarcoma, including factors in Wnt and Notch
      signaling pathways. CONCLUSION/SIGNIFICANCE: The results presented in this study
      demonstrated that over-expression of miR-34a could inhibit the tumor growth and
      metastasis of osteosarcoma probably through down regulating c-Met. And there are
      other putative miR-34a target genes beside c-Met which could potentially be key
      players in the development of osteosarcoma. Since pulmonary metastases are
      responsible for mortality of patient carrying osteosarcoma, miR-34a may prove to
      be a promising gene therapeutic agent. It will be interesting to further
      investigate the mechanism by which miR-34a functions as a tumor suppressor gene
      in osteosarcoma.

PMID- 22457789
TI  - Phylogenetic position of a copper age sheep (Ovis aries) mitochondrial DNA.
AB  - BACKGROUND: Sheep (Ovis aries) were domesticated in the Fertile Crescent region
      about 9,000-8,000 years ago. Currently, few mitochondrial (mt) DNA studies are
      available on archaeological sheep. In particular, no data on archaeological
      European sheep are available. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe
      the first portion of mtDNA sequence of a Copper Age European sheep. DNA was
      extracted from hair shafts which were part of the clothes of the so-called
      Tyrolean Iceman or Otzi (5,350-5,100 years before present). Mitochondrial DNA (a
      total of 2,429 base pairs, encompassing a portion of the control region,
      tRNA(Phe), a portion of the 12S rRNA gene, and the whole cytochrome B gene) was
      sequenced using a mixed sequencing procedure based on PCR amplification and 454
      sequencing of pooled amplification products. We have compared the sequence with
      the corresponding sequence of 334 extant lineages. CONCLUSIONS/SIGNIFICANCE: A
      phylogenetic network based on a new cladistic notation for the mitochondrial
      diversity of domestic sheep shows that the Otzi's sheep falls within haplogroup
      B, thus demonstrating that sheep belonging to this haplogroup were already
      present in the Alps more than 5,000 years ago. On the other hand, the lineage of
      the Otzi's sheep is defined by two transitions (16147, and 16440) which,
      assembled together, define a motif that has not yet been identified in modern
      sheep populations.

PMID- 22457790
TI  - Patterns of diversity in soft-bodied meiofauna: dispersal ability and body size
      matter.
AB  - BACKGROUND: Biogeographical and macroecological principles are derived from
      patterns of distribution in large organisms, whereas microscopic ones have often
      been considered uninteresting, because of their supposed wide distribution. Here,
      after reporting the results of an intensive faunistic survey of marine
      microscopic animals (meiofauna) in Northern Sardinia, we test for the effect of
      body size, dispersal ability, and habitat features on the patterns of
      distribution of several groups. METHODOLOGY/PRINCIPAL FINDINGS: As a dataset we
      use the results of a workshop held at La Maddalena (Sardinia, Italy) in September
      2010, aimed at studying selected taxa of soft-bodied meiofauna (Acoela, Annelida,
      Gastrotricha, Nemertodermatida, Platyhelminthes and Rotifera), in conjunction
      with data on the same taxa obtained during a previous workshop hosted at Tjarno
      (Western Sweden) in September 2007. Using linear mixed effects models and model
      averaging while accounting for sampling bias and potential pseudoreplication, we
      found evidence that: (1) meiofaunal groups with more restricted distribution are
      the ones with low dispersal potential; (2) meiofaunal groups with higher
      probability of finding new species for science are the ones with low dispersal
      potential; (3) the proportion of the global species pool of each meiofaunal group
      present in each area at the regional scale is negatively related to body size,
      and positively related to their occurrence in the endobenthic habitat.
      CONCLUSION/SIGNIFICANCE: Our macroecological analysis of meiofauna, in the
      framework of the ubiquity hypothesis for microscopic organisms, indicates that
      not only body size but mostly dispersal ability and also occurrence in the
      endobenthic habitat are important correlates of diversity for these understudied
      animals, with different importance at different spatial scales. Furthermore,
      since the Western Mediterranean is one of the best-studied areas in the world,
      the large number of undescribed species (37%) highlights that the census of
      marine meiofauna is still very far from being complete.

PMID- 22457791
TI  - SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty
      acids.
AB  - Increased metabolism is a requirement for tumor cell proliferation. To understand
      the dependence of tumor cells on fatty acid metabolism, we evaluated various
      nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that
      depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116
      colon cancer cells results in cytotoxicity that is reversible by addition of
      exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is
      depleted. We used this fatty-acid rescue strategy to characterize several small
      molecule inhibitors of fatty acid synthesis, including identification of TOFA as
      a potent SCD1 inhibitor, representing a previously undescribed activity for this
      compound. Reference FASN and ACC inhibitors show cytotoxicity that is less
      pronounced than that of TOFA, and fatty-acid rescue profiles consistent with
      their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar
      cytotoxicity that is offset by at least two orders of magnitude by exogenous
      oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data
      outline an effective strategy for interrogation of on-mechanism potency and
      pathway-node-specificity of fatty acid synthesis inhibitors, establish an
      unambiguous link between fatty acid synthesis and cancer cell survival, and point
      toward SCD1 as a key target in this pathway.

PMID- 22457792
TI  - Context-dependency in the effects of nutrient loading and consumers on the
      availability of space in marine rocky environments.
AB  - BACKGROUND: Enhanced nutrient loading and depletion of consumer populations
      interact to alter the structure of aquatic plant communities. Nonetheless,
      variation between adjacent habitats in the relative strength of bottom-up (i.e.
      nutrients) versus top-down (i.e. grazing) forces as determinants of community
      structure across broad spatial scales remains unexplored. We experimentally
      assessed the importance of grazing pressure and nutrient availability on the
      development of macroalgal assemblages and the maintenance of unoccupied space in
      habitats differing in physical conditions (i.e. intertidal versus subtidal),
      across regions of contrasting productivity (oligotrophic coasts of South
      Australia versus the more productive coasts of Eastern Australia).
      METHODOLOGY/PRINCIPAL FINDINGS: In Eastern Australia, grazers were effective in
      maintaining space free of macroalgae in both intertidal and subtidal habitats,
      irrespective of nutrient levels. Conversely, in South Australia, grazers could
      not prevent colonization of space by turf-forming macroalgae in subtidal habitats
      regardless of nutrients levels, yet in intertidal habitats removal of grazers
      reduced unoccupied space when nutrients were elevated. CONCLUSIONS/SIGNIFICANCE:
      Assessing the effects of eutrophication in coastal waters requires balancing our
      understanding between local consumer pressure and background oceanographic
      conditions that affect productivity. This broader-based understanding may assist
      in reconciling disproportionately large local-scale variation, a characteristic
      of ecology, with regional scale processes that are often of greater relevance to
      policy making and tractability to management.

PMID- 22457793
TI  - Integration of subthreshold and suprathreshold excitatory barrages along the
      somatodendritic axis of pyramidal neurons.
AB  - Neurons integrate inputs arriving in different cellular compartments to produce
      action potentials that are transmitted to other neurons. Because of the voltage-
      and time-dependent conductances in the dendrites and soma, summation of synaptic
      inputs is complex. To examine summation of membrane potentials and firing rates,
      we performed whole-cell recordings from layer 5 cortical pyramidal neurons in
      acute slices of the rat's somatosensory cortex. We delivered subthreshold and
      suprathreshold stimuli at the soma and several sites on the apical dendrite, and
      injected inputs that mimic synaptic barrages at individual or distributed sites.
      We found that summation of subthreshold potentials differed from that of firing
      rates. Subthreshold summation was linear when barrages were small but became
      supralinear as barrages increased. When neurons were discharging repetitively the
      rules were more diverse. At the soma and proximal apical dendrite summation of
      the evoked firing rates was predominantly sublinear whereas in the distal
      dendrite summation ranged from supralinear to sublinear. In addition, the
      integration of inputs delivered at a single location differed from that of
      distributed inputs only for suprathreshold responses. These results indicate that
      convergent inputs onto the apical dendrite and soma do not simply summate
      linearly, as suggested previously, and that distinct presynaptic afferents that
      target specific sites on the dendritic tree may perform unique sets of
      computations.

PMID- 22457794
TI  - MUC1 contributes to BPDE-induced human bronchial epithelial cell transformation
      through facilitating EGFR activation.
AB  - Although it is well known that epidermal growth factor receptor (EGFR) is
      involved in lung cancer progression, whether EGFR contributes to lung epithelial
      cell transformation is less clear. Mucin 1 (MUC1 in human and Muc1 in animals), a
      glycoprotein component of airway mucus, is overexpressed in lung tumors; however,
      its role and underlying mechanisms in early stage lung carcinogenesis is still
      elusive. This study provides strong evidence demonstrating that EGFR and MUC1 are
      involved in bronchial epithelial cell transformation. Knockdown of MUC1
      expression significantly reduced transformation of immortalized human bronchial
      epithelial cells induced by benzo[a]pyrene diol epoxide (BPDE), the active form
      of the cigarette smoke (CS) carcinogen benzo(a)pyrene (BaP)s. BPDE exposure
      robustly activated a pathway consisting of EGFR, Akt and ERK, and blocking this
      pathway significantly increased BPDE-induced cell death and inhibited cell
      transformation. Suppression of MUC1 expression resulted in EGFR destabilization
      and inhibition of the BPDE-induced activation of Akt and ERK and increase of
      cytotoxicity. These results strongly suggest an important role for EGFR in BPDE
      induced transformation, and substantiate that MUC1 is involved in lung cancer
      development, at least partly through mediating carcinogen-induced activation of
      the EGFR-mediated cell survival pathway that facilitates cell transformation.

PMID- 22457795
TI  - Low-dose Cd induces hepatic gene hypermethylation, along with the persistent
      reduction of cell death and increase of cell proliferation in rats and mice.
AB  - BACKGROUND: Cadmium (Cd) is classified as a human carcinogen probably associated
      with epigenetic changes. DNA methylation is one of epigenetic mechanisms by which
      cells control gene expression. Therefore, the present study genome-widely
      screened the methylation-altered genes in the liver of rats previously exposed to
      low-dose Cd. METHODOLOGY PRINCIPAL FINDINGS: Rats were exposed to Cd at 20
      nmol/kg every other day for 4 weeks and gene methylation was analyzed at the
      48(th) week with methylated DNA immunoprecipitation-CpG island microarray. Among
      the 1629 altered genes, there were 675 genes whose promoter CpG islands (CGIs)
      were hypermethylated, 899 genes whose promoter CGIs were hypomethylated, and 55
      genes whose promoter CGIs were mixed with hyper- and hypo-methylation. Caspase-8
      gene promoter CGIs and TNF gene promoter CGIs were hypermethylated and
      hypomethylated, respectively, along with a low apoptosis rate in Cd-treated rat
      livers. To link the aberrant methylation of caspase-8 and TNF genes to the low
      apoptosis induced by low-dose Cd, mice were given chronic exposure to low-dose Cd
      with and without methylation inhibitor (5-aza-2'-deoxyctidene, 5-aza). At the
      48(th) week after Cd exposure, livers from Cd-treated mice displayed the
      increased caspase-8 CGI methylation and decreased caspase-8 protein expression,
      along with significant increases in cell proliferation and overexpression of TGF
      beta1 and cytokeratin 8/18 (the latter is a new marker of mouse liver
      preneoplastic lesions), all which were prevented by 5-aza treatment.
      CONCLUSION/SIGNIFICANCE: These results suggest that Cd-induced global gene
      hypermethylation, most likely caspase-8 gene promoter hypermethylation that down
      regulated its expression, leading to the decreased hepatic apoptosis and
      increased preneoplastic lesions.

PMID- 22457796
TI  - Evaluation of methods for the extraction and purification of DNA from the human
      microbiome.
AB  - BACKGROUND: DNA extraction is an essential step in all cultivation-independent
      approaches to characterize microbial diversity, including that associated with
      the human body. A fundamental challenge in using these approaches has been to
      isolate DNA that is representative of the microbial community sampled.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we statistically evaluated six
      commonly used DNA extraction procedures using eleven human-associated bacterial
      species and a mock community that contained equal numbers of those eleven
      species. These methods were compared on the basis of DNA yield, DNA shearing,
      reproducibility, and most importantly representation of microbial diversity. The
      analysis of 16S rRNA gene sequences from a mock community showed that the
      observed species abundances were significantly different from the expected
      species abundances for all six DNA extraction methods used.
      CONCLUSIONS/SIGNIFICANCE: Protocols that included bead beating and/or mutanolysin
      produced significantly better bacterial community structure representation than
      methods without both of them. The reproducibility of all six methods was similar,
      and results from different experimenters and different times were in good
      agreement. Based on the evaluations done it appears that DNA extraction
      procedures for bacterial community analysis of human associated samples should
      include bead beating and/or mutanolysin to effectively lyse cells.

PMID- 22457797
TI  - EEG-based automatic classification of 'awake' versus 'anesthetized' state in
      general anesthesia using Granger causality.
AB  - BACKGROUND: General anesthesia is a reversible state of unconsciousness and
      depression of reflexes to afferent stimuli induced by administration of a
      "cocktail" of chemical agents. The multi-component nature of general anesthesia
      complicates the identification of the precise mechanisms by which anesthetics
      disrupt consciousness. Devices that monitor the depth of anesthesia are an
      important aide for the anesthetist. This paper investigates the use of effective
      connectivity measures from human electrical brain activity as a means of
      discriminating between 'awake' and 'anesthetized' state during induction and
      recovery of consciousness under general anesthesia. METHODOLOGY/PRINCIPAL
      FINDINGS: Granger Causality (GC), a linear measure of effective connectivity, is
      utilized in automated classification of 'awake' versus 'anesthetized' state using
      Linear Discriminant Analysis and Support Vector Machines (with linear and non
      linear kernel). Based on our investigations, the most characteristic change of GC
      observed between the two states is the sharp increase of GC from frontal to
      posterior regions when the subject was anesthetized, and reversal at recovery of
      consciousness. Features derived from the GC estimates resulted in classification
      of 'awake' and 'anesthetized' states in 21 patients with maximum average
      accuracies of 0.98 and 0.95, during loss and recovery of consciousness
      respectively. The differences in linear and non-linear classification are not
      statistically significant, implying that GC features are linearly separable,
      eliminating the need for a complex and computationally expensive non-linear
      classifier. In addition, the observed GC patterns are particularly interesting in
      terms of a physiological interpretation of the disruption of consciousness by
      anesthetics. Bidirectional interaction or strong unidirectional interaction in
      the presence of a common input as captured by GC are most likely related to
      mechanisms of information flow in cortical circuits. CONCLUSIONS/SIGNIFICANCE: GC
      based features could be utilized effectively in a device for monitoring depth of
      anesthesia during surgery.

PMID- 22457798
TI  - Reanalysis and simulation suggest a phylogenetic microarray does not accurately
      profile microbial communities.
AB  - The second generation (G2) PhyloChip is designed to detect over 8700 bacteria and
      archaeal and has been used over 50 publications and conference presentations.
      Many of those publications reveal that the PhyloChip measures of species richness
      greatly exceed statistical estimates of richness based on other methods. An
      examination of probes downloaded from Greengenes suggested that the system may
      have the potential to distort the observed community structure. This may be due
      to the sharing of probes by taxa; more than 21% of the taxa in that downloaded
      data have no unique probes. In-silico simulations using these data showed that a
      population of 64 taxa representing a typical anaerobic subterranean community
      returned 96 different taxa, including 15 families incorrectly called present and
      19 families incorrectly called absent. A study of nasal and oropharyngeal
      microbial communities by Lemon et al (2010) found some 1325 taxa using the G2
      PhyloChip, however, about 950 of these taxa have, in the downloaded data, no
      unique probes and cannot be definitively called present. Finally, data from
      Brodie et al (2007), when re-examined, indicate that the abundance of the
      majority of detected taxa, are highly correlated with one another, suggesting
      that many probe sets do not act independently. Based on our analyses of
      downloaded data, we conclude that outputs from the G2 PhyloChip should be treated
      with some caution, and that the presence of taxa represented solely by non-unique
      probes be independently verified.

PMID- 22457800
TI  - A macroecological analysis of SERA derived forest heights and implications for
      forest volume remote sensing.
AB  - Individual trees have been shown to exhibit strong relationships between DBH,
      height and volume. Often such studies are cited as justification for forest
      volume or standing biomass estimation through remote sensing. With resolution of
      common satellite remote sensing systems generally too low to resolve individuals,
      and a need for larger coverage, these systems rely on descriptive heights, which
      account for tree collections in forests. For remote sensing and allometric
      applications, this height is not entirely understood in terms of its location.
      Here, a forest growth model (SERA) analyzes forest canopy height relationships
      with forest wood volume. Maximum height, mean, H100, and Lorey's height are
      examined for variability under plant number density, resource and species. Our
      findings, shown to be allometrically consistent with empirical measurements for
      forested communities world-wide, are analyzed for implications to forest remote
      sensing techniques such as LiDAR and RADAR. Traditional forestry measures of
      maximum height, and to a lesser extent H100 and Lorey's, exhibit little
      consistent correlation with forest volume across modeled conditions. The
      implication is that using forest height to infer volume or biomass from remote
      sensing requires species and community behavioral information to infer accurate
      estimates using height alone. SERA predicts mean height to provide the most
      consistent relationship with volume of the height classifications studied and
      overall across forest variations. This prediction agrees with empirical data
      collected from conifer and angiosperm forests with plant densities ranging
      between 102-106 plants/hectare and heights 6-49 m. Height classifications
      investigated are potentially linked to radar scattering centers with implications
      for allometry. These findings may be used to advance forest biomass estimation
      accuracy through remote sensing. Furthermore, Lorey's height with its specific
      relationship to remote sensing physics is recommended as a more universal
      indicator of volume when using remote sensing than achieved using either maximum
      height or H100.

PMID- 22457799
TI  - Mirror symmetric bimanual movement priming can increase corticomotor excitability
      and enhance motor learning.
AB  - Repetitive mirror symmetric bilateral upper limb may be a suitable priming
      technique for upper limb rehabilitation after stroke. Here we demonstrate
      neurophysiological and behavioural after-effects in healthy participants after
      priming with 20 minutes of repetitive active-passive bimanual wrist flexion and
      extension in a mirror symmetric pattern with respect to the body midline (MIR)
      compared to an control priming condition with alternating flexion-extension
      (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor
      excitability (CME) of the passive hemisphere remained elevated compared to
      baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase
      in the size of motor evoked potentials in ECR and FCR. Short and long-latency
      intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and
      interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI
      differed between patterns, with less LICI after MIR compared with ALT, and an
      effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR
      compared with ALT and baseline. There was no effect of pattern on SAI or FCR H
      reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had
      participants complete a timed manual dexterity motor learning task with the
      passive hand during, immediately after, and 24 hours after MIR or control
      priming. The rate of task completion was faster with MIR priming compared to
      control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement
      facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR,
      MEPs were consistently facilitated before and after MIR, demonstrating no
      degradation of selective muscle activation. In summary, mirror symmetric active
      passive bimanual movement increases CME and can enhance motor learning without
      degradation of muscle selectivity. These findings rationalise the use of mirror
      symmetric bimanual movement as a priming modality in post-stroke upper limb
      rehabilitation.

PMID- 22457801
TI  - Identification of early zygotic genes in the yellow fever mosquito Aedes aegypti
      and discovery of a motif involved in early zygotic genome activation.
AB  - During early embryogenesis the zygotic genome is transcriptionally silent and all
      mRNAs present are of maternal origin. The maternal-zygotic transition marks the
      time over which embryogenesis changes its dependence from maternal RNAs to
      zygotically transcribed RNAs. Here we present the first systematic investigation
      of early zygotic genes (EZGs) in a mosquito species and focus on genes involved
      in the onset of transcription during 2-4 hr. We used transcriptome sequencing to
      identify the "pure" (without maternal expression) EZGs by analyzing transcripts
      from four embryonic time ranges of 0-2, 2-4, 4-8, and 8-12 hr, which includes the
      time of cellular blastoderm formation and up to the start of gastrulation. Blast
      of 16,789 annotated transcripts vs. the transcriptome reads revealed evidence for
      63 (P<0.001) and 143 (P<0.05) nonmaternally derived transcripts having a
      significant increase in expression at 2-4 hr. One third of the 63 EZG transcripts
      do not have predicted introns compared to 10% of all Ae. aegypti genes. We have
      confirmed by RT-PCR that zygotic transcription starts as early as 2-3 hours. A
      degenerate motif VBRGGTA was found to be overrepresented in the upstream
      sequences of the identified EZGs using a motif identification software called
      SCOPE. We find evidence for homology between this motif and the TAGteam motif
      found in Drosophila that has been implicated in EZG activation. A 38 bp sequence
      in the proximal upstream sequence of a kinesin light chain EZG (KLC2.1) contains
      two copies of the mosquito motif. This sequence was shown to support EZG
      transcription by luciferase reporter assays performed on injected early embryos,
      and confers early zygotic activity to a heterologous promoter from a divergent
      mosquito species. The results of these studies are consistent with the model of
      early zygotic genome activation via transcriptional activators, similar to what
      has been found recently in Drosophila.

PMID- 22457802
TI  - Carbon monoxide induced erythroid differentiation of K562 cells mimics the
      central macrophage milieu in erythroblastic islands.
AB  - Growing evidence supports the role of erythroblastic islands (EI) as
      microenvironmental niches within bone marrow (BM), where cell-cell attachments
      are suggested as crucial for erythroid maturation. The inducible form of the
      enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in
      erythroblasts where hemoglobin (Hb) is synthesized. Yet, the central macrophage,
      which retains high HO-1 activity, might be suitable to take over degradation of
      extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas
      molecule--CO can transfer from the macrophage to surrounding erythroblasts
      directly via their tightly attached membranes in the terminal differentiation
      stage.Based on the above, the study hypothesized CO to have a role in erythroid
      maturation. Thus, the effect of CO gas as a potential erythroid differentiation
      inducer on the common model for erythroid progenitors, K562 cells, was explored.
      Cells were kept under oxygen lacking environment to mimic BM conditions. Nitrogen
      anaerobic atmosphere (N2A) served as control for CO atmosphere (COA). Under both
      atmospheres cells proliferation ceased: in N2A due to cell death, while in COA as
      a result of erythroid differentiation. Maturation was evaluated by increased
      glycophorin A expression and Hb concentration. Addition of 1%CO only to N2A, was
      adequate for maintaining cell viability. Yet, the average Hb concentration was
      low as compared to COA. This was validated to be the outcome of diversified
      maturation stages of the progenitor's population.In fact, the above scenario
      mimics the in vivo EI conditions, where at any given moment only a minute portion
      of the progenitors proceeds into terminal differentiation. Hence, this model
      might provide a basis for further molecular investigations of the EI
      structure/function relationship.

PMID- 22457803
TI  - Cell fusion reprogramming leads to a specific hepatic expression pattern during
      mouse bone marrow derived hepatocyte formation in vivo.
AB  - The fusion of bone marrow (BM) hematopoietic cells with hepatocytes to generate
      BM derived hepatocytes (BMDH) is a natural process, which is enhanced in damaged
      tissues. However, the reprogramming needed to generate BMDH and the identity of
      the resultant cells is essentially unknown. In a mouse model of chronic liver
      damage, here we identify a modification in the chromatin structure of the
      hematopoietic nucleus during BMDH formation, accompanied by the loss of the key
      hematopoietic transcription factor PU.1/Sfpi1 (SFFV proviral integration 1) and
      gain of the key hepatic transcriptional regulator HNF-1A homeobox A (HNF
      1A/Hnf1a). Through genome-wide expression analysis of laser captured BMDH, a
      differential gene expression pattern was detected and the chromatin changes
      observed were confirmed at the level of chromatin regulator genes. Similarly,
      Tranforming Growth Factor-beta1 (TGF-beta(1)) and neurotransmitter (e.g.
      Prostaglandin E Receptor 4 [Ptger4]) pathway genes were over-expressed. In
      summary, in vivo BMDH generation is a process in which the hematopoietic cell
      nucleus changes its identity and acquires hepatic features. These BMDHs have
      their own cell identity characterized by an expression pattern different from
      hematopoietic cells or hepatocytes. The role of these BMDHs in the liver requires
      further investigation.

PMID- 22457804
TI  - Risk of stillbirth in the relation to water disinfection by-products: a
      population-based case-control study in Taiwan.
AB  - BACKGROUND: Few epidemiological studies that have assessed the relation between
      water disinfection by-products (DBPs) and the risk of stillbirth provide
      inconsistent results. The objective was to assess the relation between exposure
      to water disinfection by-products and the risk of stillbirth. METHODS: We
      conducted a population-based case-control study of 3,289 cases of stillbirth and
      a random sample of 32,890 control subjects from 396,049 Taiwanese newborns in
      2001-2003 using information from the Birth Registry and Waterworks Registry in
      Taiwan. We compared the risk of stillbirth in four disinfection by-product
      exposure categories based on the levels of total trihalomethanes (TTHMs)
      representing high (TTHMs 20+ ug/L), medium (TTHMs 10-19 ug/L), low exposure
      (TTHMs 5-9 ug/L), and 0-4 ug/L as the reference category. In addition, we
      conducted a meta-analysis of the results from the present and 5 previous studies
      focusing on stillbirth. FINDINGS: In logistic regression analysis adjusting for
      gender, maternal age, plurality, conception of season and population density of
      the municipality where the mother lived during pregnancy, the odds ratio (OR) for
      stillbirth was 1.10 (95% CI 1.00-1.21) for medium exposure and 1.06 (95% 0.96
      1.17) for high exposure compared to reference category. In the meta-analysis, the
      summary odds ratio for stillbirth (1.11, 95% CI: 1.03, 1.19) was consistently
      elevated. CONCLUSIONS: The present study is consistent with the hypothesis that
      the risk of stillbirth is related to prenatal exposure to disinfection by
      products. This finding on stillbirth is consistent with previous epidemiologic
      studies, which strengthens the weight of evidence.

PMID- 22457805
TI  - Maxadilan prevents apoptosis in iPS cells and shows no effects on the pluripotent
      state or karyotype.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a structurally
      endogenous peptide with many biological roles. Maxadilan, a 61-amino acid
      vasodilatory peptide, specifically activates the PACAP type I receptor (PAC1).
      Although PAC1 has been identified in embryonic stem cells, little is known about
      its presence or effects in human induced pluripotent stem (iPS) cells. In the
      present study, we investigated the expression of PAC1 in human iPS cells by
      reverse transcriptase polymerase chain reaction (RT-PCR) and western blot
      analysis. To study the physiological effects mediated by PAC1, we evaluated the
      role of maxadilan in preventing apoptotic cell death induced by ultraviolet C
      (UVC). After exposure to UVC, the iPS cells showed a marked reduction in cell
      viability and a parallel increase of apoptotic cells, as demonstrated by WST-8
      analysis, annexin V/propidium iodide (PI) analysis and the terminal transferase
      dUTP nick end labeling (TUNEL) assay. The addition of 30 nM of maxadilan
      dramatically increased iPS cell viability and reduced the percentage of apoptotic
      cells. The anti-apoptotic effects of maxadilan were correlated to the
      downregulation of caspase-3 and caspase-9. Concomitantly, immunofluorescence,
      western blot analysis, real-time quantitative polymerase chain reaction (RT-qPCR)
      analysis and in vitro differentiation results showed that maxadilan did not
      affect the pluripotent state of iPS cells. Moreover, karyotype analysis showed
      that maxadilan did not affect the karyotype of iPS cells. In summary, these
      results demonstrate that PAC1 is present in iPS cells and that maxadilan
      effectively protects iPS cells against UVC-induced apoptotic cell death while not
      affecting the pluripotent state or karyotype.

PMID- 22457806
TI  - Suppression of adiponectin by aberrantly glycosylated IgA1 in glomerular
      mesangial cells in vitro and in vivo.
AB  - The pathogenesis of IgA nephropathy (IgAN) may be associated with the mesangial
      deposition of aberrantly glycosylated IgA1. To identify mediators affected by
      aberrantly glycosylated IgA1 in cultured human mesangial cells (HMCs), we
      generated enzymatically modified desialylated and degalactosylated (deSial/deGal)
      IgA1. The state of deglycosylated IgA1 was confirmed by lectin binding to Helix
      aspersa (HAA) and Sambucus nigra (SNA). In the cytokine array analysis, 52
      proteins were upregulated and 34 were downregulated in HMCs after stimulation
      with deSial/deGal IgA1. Among them, the secretion of adiponectin was suppressed
      in HMCs after stimulation with deSial/deGal IgA1. HMCs expressed mRNAs for
      adiponectin and its type 1 receptor, but not the type 2 receptor. Moreover, we
      revealed a downregulation of adiponectin expression in the glomeruli of renal
      biopsy specimens from patients with IgAN compared to those with lupus nephritis.
      We also demonstrated that aberrantly glycosylated IgA1 was deposited in the
      mesangium of patients with IgAN by dual staining of HAA and IgA. Moreover, the
      urinary HAA/SNA ratio of lectin binding was significantly higher in IgAN compared
      to other kidney diseases. Since adiponectin has anti-inflammatory effects,
      including the inhibition of adhesion molecules and cytokines, these data suggest
      that the local suppression of this adipokine by aberrantly glycosylated IgA1
      could be involved in the regulation of glomerular inflammation and sclerosis in
      IgAN.

PMID- 22457807
TI  - A novel high-content flow cytometric method for assessing the viability and
      damage of rat retinal ganglion cells.
AB  - PURPOSE: The aim of the study was to develop a high-content flow cytometric
      method for assessing the viability and damage of small, medium, and large retinal
      ganglion cells (RGCs) in N-methyl-D-aspartic acid (NMDA)-injury model.
      METHODS/RESULTS: Retinal toxicity was induced in rats by intravitreal injection
      of NMDA and RGCs were retrogradely labeled with Fluoro-Gold (FG). Seven days post
      NMDA injection, flatmount and flow cytometric methods were used to evaluate RGCs.
      In addition, the RGC area diameter (D((a))) obtained from retinal flatmount
      imaging were plotted versus apparent volume diameter (D((v))) obtained from flow
      cytometry for the same cumulative cell number (sequentially from small to large
      RGCs) percentile (Q) to establish their relationship for accurately determining
      RGC sizes. Good correlation (r = 0.9718) was found between D((a)) and apparent
      D((v)). Both flatmount and flow cytometric analyses of RGCs showed that 40 mM
      NMDA significantly reduced the numbers of small and medium RGCs but not large
      RGCs. Additionally, flow cytometry showed that the geometric means of FG and thy
      1 intensities in three types of RGCs decreased to 90.96+/-2.24% (P<0.05) and
      91.78+/-1.89% (P>0.05) for small, 69.62+/-2.11% (P<0.01) and 69.07+/-2.98%
      (P<0.01) for medium, and 69.68+/-6.48% (P<0.05) and 69.91+/-6.23% (P<0.05) for
      large as compared with the normal RGCs. CONCLUSION: The established flow
      cytometric method provides high-content analysis for differential evaluation of
      RGC number and status and should be useful for the evaluation of various models
      of optic nerve injury and the effects of potential neuroprotective agents.

PMID- 22457808
TI  - The cluster of miR-143 and miR-145 affects the risk for esophageal squamous cell
      carcinoma through co-regulating fascin homolog 1.
AB  - MicroRNAs (miRNAs), 18-24 nt non-coding RNAs, are thought to play important roles
      in cell proliferation, differentiation, apoptosis, and development. Recent
      studies suggest that some of the known microRNAs map to a single genomic locale
      within a single polycistronic transcript. But the roles of the cluster remain to
      be known. In order to understand the role and mechanism of a cluster of miR-143
      and miR-145 in esophageal squamous cell carcinoma (ESCC), the association of
      mature miR-143 and miR-145 expression with the risk for esophageal cancer was
      evaluated in ESCC patients with a case-control study, and target protein
      regulated by mature miRNA was analyzed in ESCC cell lines with 3'UTR luciferase
      reporter assay. The expression levels of miR-143 and miR-145 were determined in
      110 pairs of esophageal cancer tissues and adjacent normal tissues using real
      time reverse transcription PCR. The relative expression of miR-143 and miR-145
      were statistically different between cancer tissues and matched controls. The
      combined expression of miR-143 and miR-145 was significantly associated with the
      risk for esophageal cancer. Meanwhile, the reduced expression of two miRNAs in
      tumor patient was supposed to have a trend of lymph node metastases. The co
      expression pattern of miR-143 and miR-145 was analyzed with Pearson correlation.
      It showed a significant correlation between these two miRNAs expression both in
      tissues and tumor cell lines. 3'UTR luciferase reporter assay indicated that
      Fascin Homolog 1 (FSCN1) could be co-regulated by miR-143 and miR-145. The
      protein level of FSCN1 showed no significant linear correlation with miR-143 and
      miR-145 expression in ESCC cell lines with Western blotting analysis. In
      conclusion, since miR-143 and miR-145 could regulate oncogenic FSCN1 and take
      part in the modulation of metastases, the result suggested the combination
      variable of miR-143 and miR-145 as a potential biomarker for earlier diagnosis
      and prognosis of esophageal cancer.

PMID- 22457809
TI  - In ovo monitoring of smooth muscle fiber development in the chick embryo:
      diffusion tensor imaging with histologic correlation.
AB  - BACKGROUND: Magnetic resonance imaging is a noninvasive method of evaluating
      embryonic development. Magnetic resonance diffusion tensor imaging, which is
      based on the measuring the directional diffusivity of water molecules, is an
      established method of evaluating tissue structure. Prolonged imaging times have
      precluded the use of embryonic diffusion tensor imaging due to motion artifact.
      Using temperature-based motion suppression, we aimed to investigate whether
      diffusion tensor imaging can be used to monitor embryonic smooth muscle
      development in ovo, and to determine the correlation between histologically
      derived muscle fiber fraction, day of incubation and diffusion tensor imaging
      fractional anisotropy values and length of tracked fibers. METHODOLOGY/PRINCIPAL
      FINDINGS: From a set of 82 normally developing fertile chicken eggs, 5 eggs were
      randomly chosen each day from incubation days 5 to 18 and cooled using a dual
      cooling technique prior to and during magnetic resonance imaging at 3.0 Tesla.
      Smooth muscle fibers of the gizzard were tracked using region of interests placed
      over the gizzard. Following imaging, the egg was cracked and the embryo was
      fixated and sectioned, and a micrograph most closely corresponding to the
      acquired magnetic resonance image was made. Smooth muscle fiber fraction was
      determined using an automated computer algorithm. CONCLUSIONS/SIGNIFICANCE: We
      show that diffusion tensor images of smooth muscle within the embryonic gizzard
      can be acquired in ovo from incubation day 11 through hatching. Length of tracked
      fibers and day of incubation were found to have statistical significance (p<0.05)
      by multiple linear regression correlation with histologic specimens of sacrificed
      embryos from day 11 of incubation through hatching. The morphologic pattern of
      development in our histologic specimens corresponds to the development of
      embryonic gizzard as reported in the literature. These results suggest that
      diffusion tensor imaging can provide a noninvasive method of evaluating in ovo
      development of smooth muscle tissue.

PMID- 22457810
TI  - Common genetic variation in the SERPINF1 locus determines overall adiposity,
      obesity-related insulin resistance, and circulating leptin levels.
AB  - OBJECTIVE: Pigment epithelium-derived factor (PEDF) belongs to the serpin family
      of peptidase inhibitors (serpin F1) and is among the most abundant glycoproteins
      secreted by adipocytes. In vitro and mouse in vivo data revealed PEDF as a
      candidate mediator of obesity-induced insulin resistance. Therefore, we assessed
      whether common genetic variation within the SERPINF1 locus contributes to adipose
      tissue-related prediabetic phenotypes in humans. SUBJECTS/METHODS: A population
      of 1,974 White European individuals at increased risk for type 2 diabetes was
      characterized by an oral glucose tolerance test with glucose and insulin
      measurements (1,409 leptin measurements) and genotyped for five tagging SNPs
      covering 100% of common genetic variation (minor allele frequency >= 0.05) in the
      SERPINF1 locus. In addition, a subgroup of 486 subjects underwent a
      hyperinsulinaemic-euglycaemic clamp and a subgroup of 340 magnetic resonance
      imaging (MRI) and spectroscopy (MRS). RESULTS: After adjustment for gender and
      age and Bonferroni correction for the number of SNPs tested, SNP rs12603825
      revealed significant association with MRI-derived total adipose tissue mass (p =
      0.0094) and fasting leptin concentrations (p = 0.0035) as well as nominal
      associations with bioelectrical impedance-derived percentage of body fat (p =
      0.0182) and clamp-derived insulin sensitivity (p = 0.0251). The association with
      insulin sensitivity was completely abolished by additional adjustment for body
      fat (p = 0.8). Moreover, the fat mass-increasing allele of SNP rs12603825 was
      significantly associated with elevated fasting PEDF concentrations (p = 0.0436),
      and the PEDF levels were robustly and positively associated with all body fat
      parameters measured and with fasting leptin concentrations (p<0.0001, all).
      CONCLUSION: In humans at increased risk for type 2 diabetes, a functional common
      genetic variant in the gene locus encoding PEDF contributes to overall body
      adiposity, obesity-related insulin resistance, and circulating leptin levels.

PMID- 22457811
TI  - Kindlins, integrin activation and the regulation of talin recruitment to
      alphaIIbbeta3.
AB  - Talins and kindlins bind to the integrin beta3 cytoplasmic tail and both are
      required for effective activation of integrin alphaIIbbeta3 and resulting high
      affinity ligand binding in platelets. However, binding of the talin head domain
      alone to beta3 is sufficient to activate purified integrin alphaIIbbeta3 in
      vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its
      re-localization to the plasma membrane and to the integrin is required for
      activation. Here we explored the mechanism whereby kindlins function as integrin
      co-activators. To test whether kindlins regulate talin recruitment to plasma
      membranes and to alphaIIbbeta3, full-length talin and kindlin recruitment to
      beta3 was studied using a reconstructed CHO cell model system that recapitulates
      agonist-induced alphaIIbbeta3 activation. Over-expression of kindlin-2, the
      endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin
      dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited
      ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin
      recruitment to the plasma membrane, as assessed by sub-cellular fractionation,
      and neither over-expression of kindlins nor depletion of kindlin-2 affected talin
      interaction with alphaIIbbeta3 in living cells, as monitored by bimolecular
      fluorescence complementation. Furthermore, talin failed to promote kindlin-2
      association with alphaIIbbeta3 in CHO cells. In addition, purified talin and
      kindlin-3, the kindlin isoform expressed in platelets, failed to promote each
      other's binding to the beta3 cytoplasmic tail in vitro. Thus, kindlins do not
      promote initial talin recruitment to alphaIIbbeta3, suggesting that they co
      activate integrin through a mechanism independent of recruitment.

PMID- 22457812
TI  - Progesterone receptor activates Msx2 expression by downregulating TNAP/Akp2 and
      activating the Bmp pathway in EpH4 mouse mammary epithelial cells.
AB  - Previously we demonstrated that EpH4 mouse mammary epithelial cells induced the
      homeobox transcription factor Msx2 either when transfected with the progesterone
      receptor (PR) or when treated with Bmp2/4. Msx2 upregulation was unaffected by
      Wnt inhibitors s-FRP or Dkk1, but was inhibited by the Bmp antagonist Noggin. We
      therefore hypothesized that PR signaling to Msx2 acts through the Bmp receptor
      pathway. Herein, we confirm that transcripts for Alk2/ActR1A, a non-canonical
      BmpR Type I, are upregulated in mammary epithelial cells overexpressing PR (EpH4
      PR). Increased phosphorylation of Smads 1,5, 8, known substrates for Alk2 and
      other BmpR Type I proteins, was observed as was their translocation to the
      nucleus in EpH4-PR cells. Analysis also showed that Tissue Non-Specific Alkaline
      Phosphatase (TNAP/Akp2) was also found to be downregulated in EpH4-PR cells. When
      an Akp2 promoter-reporter construct containing a 1/2PRE site was transfected into
      EpH4-PR cells, its expression was downregulated. Moreover, siRNA mediated
      knockdown of Akp2 increased both Alk2 and Msx2 expression. Collectively these
      data suggest that PR inhibition of Akp2 results in increased Alk2 activity,
      increased phosphorylation of Smads 1,5,8, and ultimately upregulation of Msx2.
      These studies imply that re-activation of the Akp2 gene could be helpful in
      downregulating aberrant Msx2 expression in PR+ breast cancers.

PMID- 22457813
TI  - RNA interference mediated inhibition of dengue virus multiplication and entry in
      HepG2 cells.
AB  - BACKGROUND: Dengue virus-host cell interaction initiates when the virus binds to
      the attachment receptors followed by endocytic internalization of the virus
      particle. Successful entry into the cell is necessary for infection initiation.
      Currently, there is no protective vaccine or antiviral treatment for dengue
      infection. Targeting the viral entry pathway has become an attractive therapeutic
      strategy to block infection. This study aimed to investigate the effect of
      silencing the GRP78 and clathrin-mediated endocytosis on dengue virus entry and
      multiplication into HepG2 cells. METHODOLOGY/PRINCIPAL FINDINGS: HepG2 cells were
      transfected using specific siRNAs to silence the cellular surface receptor
      (GRP78) and clathrin-mediated endocytosis pathway. Gene expression analysis
      showed a marked down-regulation of the targeted genes (87.2%, 90.3%, and 87.8%
      for GRP78, CLTC, and DNM2 respectively) in transfected HepG2 cells when measured
      by RT-qPCR. Intracellular and extracellular viral RNA loads were quantified by RT
      qPCR to investigate the effect of silencing the attachment receptor and clathrin
      mediated endocytosis on dengue virus entry. Silenced cells showed a significant
      reduction of intracellular (92.4%) and extracellular viral RNA load (71.4%)
      compared to non-silenced cells. Flow cytometry analysis showed a marked reduction
      of infected cells (89.7%) in silenced HepG2 cells compared to non-silenced cells.
      Furthermore, the ability to generate infectious virions using the plaque assay
      was reduced 1.07 log in silenced HepG2 cells. CONCLUSIONS/SIGNIFICANCE: Silencing
      the attachment receptor and clathrin-mediated endocytosis using siRNA could
      inhibit dengue virus entry and multiplication into HepG2 cells. This leads to
      reduction of infected cells as well as the viral load, which might function as a
      unique and promising therapeutic agent for attenuating dengue infection and
      prevent the development of dengue fever to the severe life-threatening DHF or
      DSS. Furthermore, a decrease of viremia in humans can result in the reduction of
      infected vectors and thus, halt of the transmission cycle.

PMID- 22457814
TI  - The p21-dependent radiosensitization of human breast cancer cells by MLN4924, an
      investigational inhibitor of NEDD8 activating enzyme.
AB  - Radiotherapy is a treatment choice for local control of breast cancer. However,
      intrinsic radioresistance of cancer cells limits therapeutic efficacy. We have
      recently validated that SCF (SKP1, Cullins, and F-box protein) E3 ubiquitin
      ligase is an attractive radiosensitizing target. Here we tested our hypothesis
      that MLN4924, a newly discovered investigational small molecule inhibitor of NAE
      (NEDD8 Activating Enzyme) that inactivates SCF E3 ligase, could act as a novel
      radiosensitizing agent in breast cancer cells. Indeed, we found that MLN4924
      effectively inhibited cullin neddylation, and sensitized breast cancer cells to
      radiation with a sensitivity enhancement ratio (SER) of 1.75 for SK-BR-3 cells
      and 1.32 for MCF7 cells, respectively. Mechanistically, MLN4924 significantly
      enhanced radiation-induced G2/M arrest in SK-BR-3 cells, but not in MCF7 cells at
      early time point, and enhanced radiation-induced apoptosis in both lines at later
      time point. However, blockage of apoptosis by Z-VAD failed to abrogate MLN4924
      radiosensitization, suggesting that apoptosis was not causally related. We
      further showed that MLN4924 failed to enhance radiation-induced DNA damage
      response, but did cause minor delay in DNA damage repair. Among a number of
      tested SCF E3 substrates known to regulate growth arrest, apoptosis and DNA
      damage response, p21 was the only one showing an enhanced accumulation in MLN4924
      radiation combination group, as compared to the single treatment groups.
      Importantly, p21 knockdown via siRNA partialy inhibited MLN4924-induced G2/M
      arrest and radiosensitization, indicating a causal role played by p21. Our study
      suggested that MLN4924 could be further developed as a novel class of
      radiosensitizer for the treatment of breast cancer.

PMID- 22457815
TI  - Prognostic value of survivin in patients with non-small cell lung carcinoma: a
      systematic review with meta-analysis.
AB  - PURPOSE: The potential prognostic value of survivin in resected non-small cell
      lung carcinoma (NSCLC) is variably reported. The objective of this study was to
      conduct a systematic review of literatures evaluating survivin expression in
      resected NSCLC as a prognostic indicator. METHODS: Relevant literatures were
      identified using PubMed, EMBASE and Chinese Biomedicine Databases. We present the
      results of a meta-analysis of the association between survivin expression and
      overall survival (OS) in NSCLC patients. Studies were pooled and summary hazard
      ratios (HR) were calculated. Subgroup analyses and publication bias were also
      conducted. RESULTS: We performed a final analysis of 2703 patients from 28
      evaluable studies. Combined HRs suggested that survivin overexpression had an
      unfavorable impact on NSCLC patients' survival with no evidence of any
      significant publication bias (HR = 2.03, 95%CI: 1.78-2.33, Egger's test, P =
      0.24) and no severe heterogeneity between studies (I2  =  26.9%). Its effect also
      appeared significant when stratified according to the studies categorized by
      histological type, HR estimate, patient race, cutoff point (5%, 10%), detection
      methods and literature written language except for disease stage. Survivin was
      identified as a prognostic marker of advanced-stage NSCLC (HR = 1.93, 95%CI: 1.49
      2.51), but not early-stage NSCLC (HR = 1.97, 95%CI: 0.76-5.14), in spite of the
      combined data being relatively small. CONCLUSION: This study shows that survivin
      expression appears to be a pejorative prognostic factor in terms of overall
      survival in surgically treated NSCLC. Large prospective studies are now needed to
      confirm the clinical utility of survivin as an independent prognostic marker.

PMID- 22457816
TI  - Association of the MTHFR A1298C variant with unexplained severe male infertility.
AB  - The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main
      regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation
      reactions. The influence of MTHFR variants on male infertility is not completely
      understood. The objective of this study was to analyze the distribution of the
      MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length
      Polymorphism (RFLP) in a case group consisting of 344 men with unexplained
      reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic
      controls. The Chi square test was used to analyze the genotype distributions of
      MTHFR polymorphisms. Our data indicated a lack of association of the C677T
      variant with infertility. However, the homozygous (C/C) A1298C polymorphism of
      the MTHFR gene was present at a statistically high significance in severe
      oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval
      CI = 1.27-8.238; p = 0.01431). The genotype distribution of the A1298C variants
      showed significant deviation from the expected Hardy-Weinberg equilibrium,
      suggesting that purifying selection may be acting on the 1298CC genotype. Further
      studies are necessary to determine the influence of the environment, especially
      the consumption of diet folate on sperm counts of men with different MTHFR
      variants.

PMID- 22457817
TI  - Hormone treatment, estrogen receptor polymorphisms and mortality: a prospective
      cohort study.
AB  - BACKGROUND: The association between hormone treatment (HT) and mortality remains
      controversial. This study aimed to determine whether the risk of mortality
      associated with HT use varies depending on the specific characteristics of
      treatment and genetic variability in terms of the estrogen receptor.
      METHODOLOGY/PRINCIPAL FINDINGS: A prospective, population-based study of 5135
      women aged 65 years and older who were recruited from three cities in France and
      followed over six years. Detailed information related to HT use was obtained and
      five estrogen receptor polymorphisms were genotyped. The total follow-up was
      25,436 person-years and during this time 352 women died. Cancer (36.4%) and
      cardiovascular disease (19.3%) were the major causes of death. Cox proportional
      hazards models adjusted for age, education, centre, living situation,
      comorbidity, depression, physical and mental incapacities, indicated no
      significant association between HT and mortality, regardless of the type or
      duration of treatment, or the age at initiation. However, the association between
      HT and all-cause or cancer-related mortality varied across women, with
      significant interactions identified with three estrogen receptor polymorphisms (p
      values = 0.004 to 0.03) in adjusted analyses. Women carrying the C allele of ESR1
      rs2234693 had a decreased risk of all-cause mortality with HT (HR: 0.42, 95% CI:
      0.18-0.97), while in stark contrast, those homozygous for the T allele had a
      significantly increased risk of cancer-related mortality (HR: 3.18, 95% CI: 1.23
      8.20). The findings were similar for ESR1 rs9340799 and ESR2 rs1271572.
      CONCLUSIONS/SIGNIFICANCE: The risk of mortality was not associated with HT
      duration, type or age at initiation. It was however not equal across all women,
      with some women appearing genetically more vulnerable to the effects of HT in
      terms of their estrogen receptor genotype. These findings, if confirmed in
      another independent study, may help explain the differential susceptibility of
      women to the beneficial or adverse effects of HT.

PMID- 22457818
TI  - Genetic evidence of functional ficolin-2 haplotype as susceptibility factor in
      cutaneous leishmaniasis.
AB  - BACKGROUND: Ficolin-2 coded by FCN2 gene is a soluble serum protein that plays an
      important role in innate immunity. In this study, we analyzed five functional
      polymorphisms of the FCN2 gene for their possible association with cutaneous
      leishmaniasis. METHODS: Initially we screened 40 Syrian Arabs for the entire FCN2
      gene. We investigated the contribution of FCN2 functional variants in 226
      patients with cutaneous leishmaniasis and 286 healthy controls from Syria.
      Polymorphisms in the promoter regions (-986G/A, -602G/A, -4A/G) of the FCN2 gene
      were assessed by TaqMan real time PCR, whereas polymorphisms in exon8 (+6359C/T
      and +6424G/T) were assessed by DNA sequencing. We also measured serum ficolin-2
      levels in 70 control Syrian Arabs and correlated the serum concentrations to FCN2
      genotypes and haplotypes respectively. RESULTS: Nine new FCN2 variants including
      two with non synonymous substitutions in exon6 and exon8 were observed. The
      homozygous genotypes +6424T/T were distributed more in controls and none in
      patients (P = 0.04). The AGACG haplotype were observed more in patients than in
      controls (OR = 2.0, 95%CI 1.2-3.4, P = 0.006). The serum ficolin-2 levels were
      significantly distributed among the reconstructed ficolin-2 haplotypes (P<0.008)
      and the haplotype AGACG was observed with higher ficolin-2 levels in 70 control
      individuals. CONCLUSION: Our results demonstrate a significant association of
      FCN2 AGACG haplotype with cutaneous leishmaniasis in a Syrian Arab population.
      These first results provide a basis for a future study that could confirm or
      disprove possible relationships between FCN2 gene polymorphisms with cutaneous
      leishmaniasis.

PMID- 22457819
TI  - Antecedent avian immunity limits tangential transmission of West Nile virus to
      humans.
AB  - BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus maintained and
      amplified among birds and tangentially transmitted to humans and horses which may
      develop terminal neuroinvasive disease. Outbreaks typically have a three-year
      pattern of silent introduction, rapid amplification and subsidence, followed by
      intermittent recrudescence. Our hypothesis that amplification to outbreak levels
      is contingent upon antecedent seroprevalence within maintenance host populations
      was tested by tracking WNV transmission in Los Angeles, California from 2003
      through 2011. METHODS: Prevalence of antibodies against WNV was monitored weekly
      in House Finches and House Sparrows. Tangential or spillover transmission was
      measured by seroconversions in sentinel chickens and by the number of West Nile
      neuroinvasive disease (WNND) cases reported to the Los Angeles County Department
      of Public Health. RESULTS: Elevated seroprevalence in these avian populations was
      associated with the subsidence of outbreaks and in the antecedent dampening of
      amplification during succeeding years. Dilution of seroprevalence by recruitment
      resulted in the progressive loss of herd immunity following the 2004 outbreak,
      leading to recrudescence during 2008 and 2011. WNV appeared to be a significant
      cause of death in these avian species, because the survivorship of antibody
      positive birds significantly exceeded that of antibody negative birds. Cross
      correlation analysis showed that seroprevalence was negatively correlated prior
      to the onset of human cases and then positively correlated, peaking at 4-6 weeks
      after the onset of tangential transmission. Antecedent seroprevalence during
      winter (Jan - Mar) was negatively correlated with the number of WNND cases during
      the succeeding summer (Jul-Sep). CONCLUSIONS: Herd immunity levels within after
      hatching year avian maintenance host populations <10% during the antecedent late
      winter and spring period were followed on three occasions by outbreaks of WNND
      cases during the succeeding summer. Because mosquitoes feed almost exclusively on
      these avian species, amplification was directly related to the availability of
      receptive non-immune hosts.

PMID- 22457820
TI  - Prostate cancer risk is not altered by TP53AIP1 germline mutations in a German
      case-control series.
AB  - Prostate cancer susceptibility has previously been associated with truncating
      germline variants in the gene TP53AIP1 (tumor protein p53 regulated apoptosis
      inducing protein 1). For two apparently recurrent mutations (p.Q22fs and p.S32X)
      a remarkable OR of 5.1 was reported for prostate cancer risk. Since these
      findings have not been validated so far, we genotyped p.Q22fs and p.S32X in two
      German series with a total of 1,207 prostate cancer cases and 1,495 controls. The
      truncating variants were not significantly associated with prostate cancer in
      none of the two cohorts, nor in the combined analysis [odds ratio (OR) = 1.16;
      95% confidence interval (CI 95%) = 0.62-2.15; p = 0.66]. Carriers showed no
      significant differences in family history of prostate cancer, age at diagnosis,
      Gleason score or PSA at diagnosis when compared to non-carrier prostate cancer
      cases. The large sample size of the combined cohort rejects a high-risk effect
      greater than 2.2 and indicates a limited role of TP53AIP1 in prostate cancer
      predisposition.

PMID- 22457821
TI  - Brief exposure to sensory cues elicits stimulus-nonspecific general sensitization
      in an insect.
AB  - The effect of repeated exposure to sensory stimuli, with or without reward is
      well known to induce stimulus-specific modifications of behaviour, described as
      different forms of learning. In recent studies we showed that a brief single pre
      exposure to the female-produced sex pheromone or even a predator sound can
      increase the behavioural and central nervous responses to this pheromone in males
      of the noctuid moth Spodoptera littoralis. To investigate if this increase in
      sensitivity might be restricted to the pheromone system or is a form of general
      sensitization, we studied here if a brief pre-exposure to stimuli of different
      modalities can reciprocally change behavioural and physiological responses to
      olfactory and gustatory stimuli. Olfactory and gustatory pre-exposure and
      subsequent behavioural tests were carried out to reveal possible intra- and cross
      modal effects. Attraction to pheromone, monitored with a locomotion compensator,
      increased after exposure to olfactory and gustatory stimuli. Behavioural
      responses to sucrose, investigated using the proboscis extension reflex,
      increased equally after pre-exposure to olfactory and gustatory cues. Pheromone
      specific neurons in the brain and antennal gustatory neurons did, however, not
      change their sensitivity after sucrose exposure. The observed intra- and
      reciprocal cross-modal effects of pre-exposure may represent a new form of
      stimulus-nonspecific general sensitization originating from modifications at
      higher sensory processing levels.

PMID- 22457822
TI  - The role of the Parkinson's disease gene PARK9 in essential cellular pathways and
      the manganese homeostasis network in yeast.
AB  - YPK9 (Yeast PARK9; also known as YOR291W) is a non-essential yeast gene predicted
      by sequence to encode a transmembrane P-type transport ATPase. However, its
      substrate specificity is unknown. Mutations in the human homolog of YPK9,
      ATP13A2/PARK9, have been linked to genetic forms of early onset parkinsonism. We
      previously described a strong genetic interaction between Ypk9 and another
      Parkinson's disease (PD) protein alpha-synuclein in multiple model systems, and a
      role for Ypk9 in manganese detoxification in yeast. In humans, environmental
      exposure to toxic levels of manganese causes a syndrome similar to PD and is thus
      an environmental risk factor for the disease. How manganese contributes to
      neurodegeneration is poorly understood. Here we describe multiple genome-wide
      screens in yeast aimed at defining the cellular function of Ypk9 and the
      mechanisms by which it protects cells from manganese toxicity. In physiological
      conditions, we found that Ypk9 genetically interacts with essential genes
      involved in cellular trafficking and the cell cycle. Deletion of Ypk9 sensitizes
      yeast cells to exposure to excess manganese. Using a library of non-essential
      gene deletions, we screened for additional genes involved in tolerance to excess
      manganese exposure, discovering several novel pathways involved in manganese
      homeostasis. We defined the dependence of the deletion strain phenotypes in the
      presence of manganese on Ypk9, and found that Ypk9 deletion modifies the
      manganese tolerance of only a subset of strains. These results confirm a role for
      Ypk9 in manganese homeostasis and illuminates cellular pathways and biological
      processes in which Ypk9 likely functions.

PMID- 22457823
TI  - Puerarin induces mitochondria-dependent apoptosis in hypoxic human pulmonary
      arterial smooth muscle cells.
AB  - BACKGROUND: Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial
      hypertension (PAH) is caused in part by decreased apoptosis in pulmonary artery
      smooth muscle cells (PASMCs). Puerarin, an isoflavone purified from the Chinese
      medicinal herb kudzu, ameliorates chronic hypoxic PAH in animal models. Here we
      investigated the effects of puerarin on apoptosis of hypoxic human PASMCs
      (HPASMCs), and to determine the possible underlying mechanisms.
      METHODOLOGY/PRINCIPAL FINDINGS: HPASMCs were cultured for 24 h in normoxia or
      hypoxia (5% O2) conditions with and without puerarin. Cell number and viability
      were determined with a hemacytometer or a cell counting kit. Apoptosis was
      detected with a TUNEL test, rhodamine-123 (R-123) fluorescence, a colorimetric
      assay, western blots, immunohistochemical staining and RT-PCR. Hypoxia inhibited
      mitochondria-dependent apoptosis and promoted HPASMC growth. In contrast, after
      puerarin (50 uM or more) intervention, cell growth was inhibited and apoptosis
      was observed. Puerarin-induced apoptosis in hypoxic HPASMCs was accompanied by
      reduced mitochondrial membrane potential, cytochrome c release from the
      mitochondria, caspase-9 activation, and Bcl-2 down-regulation with concurrent Bax
      up-regulation. CONCLUSIONS/SIGNIFICANCE: Puerarin promoted apoptosis in hypoxic
      HPASMCs by acting on the mitochondria-dependent pathway. These results suggest a
      new mechanism of puerarin relevant to the management of clinical hypoxic
      pulmonary hypertension.

PMID- 22457824
TI  - Ubiquitination of CXCR7 controls receptor trafficking.
AB  - The chemokine receptor CXCR7 binds CXCL11 and CXCL12 with high affinity,
      chemokines that were previously thought to bind exclusively to CXCR4 and CXCR3,
      respectively. Expression of CXCR7 has been associated with cardiac development as
      well as with tumor growth and progression. Despite having all the canonical
      features of G protein-coupled receptors (GPCRs), the signalling pathways
      following CXCR7 activation remain controversial, since unlike typical chemokine
      receptors, CXCR7 fails to activate Galpha(i)-proteins. CXCR7 has recently been
      shown to interact with beta-arrestins and such interaction has been suggested to
      be responsible for G protein-independent signals through ERK-1/2 phosphorylation.
      Signal transduction by CXCR7 is controlled at the membrane by the process of GPCR
      trafficking. In the present study we investigated the regulatory processes
      triggered by CXCR7 activation as well as the molecular interactions that
      participate in such processes. We show that, CXCR7 internalizes and recycles back
      to the cell surface after agonist exposure, and that internalization is not only
      beta-arrestin-mediated but also dependent on the Serine/Threonine residues at the
      C-terminus of the receptor. Furthermore we describe, for the first time, the
      constitutive ubiquitination of CXCR7. Such ubiquitination is a key modification
      responsible for the correct trafficking of CXCR7 from and to the plasma membrane.
      Moreover, we found that CXCR7 is reversibly de-ubiquitinated upon treatment with
      CXCL12. Finally, we have also identified the Lysine residues at the C-terminus of
      CXCR7 to be essential for receptor cell surface delivery. Together these data
      demonstrate the differential regulation of CXCR7 compared to the related CXCR3
      and CXCR4 receptors, and highlight the importance of understanding the molecular
      determinants responsible for this process.

PMID- 22457825
TI  - The tumor suppressive role of eIF3f and its function in translation inhibition
      and rRNA degradation.
AB  - Deregulated translation plays an important role in human cancer. We previously
      reported decreased eukaryotic initiation factor 3 subunit f (eIF3f) expression in
      pancreatic cancer. Whether decreased eIF3f expression can transform normal
      epithelial cells is not known. In our current study, we found evidence that
      stable knockdown of eIF3f in normal human pancreatic ductal epithelial cells
      increased cell size, nuclear pleomorphism, cytokinesis defects, cell
      proliferation, clonogenicity, apoptotic resistance, migration, and formation of 3
      dimensional irregular masses. Our findings support the tumor suppressive role of
      eIF3f in pancreatic cancer. Mechanistically, we found that eIF3f inhibited both
      cap-dependent and cap-independent translation. An increase in the ribosomal RNA
      (rRNA) level was suggested to promote the generation of cancer. The regulatory
      mechanism of rRNA degradation in mammals is not well understood. We demonstrated
      here that eIF3f promotes rRNA degradation through direct interaction with
      heterogeneous nuclear ribonucleoprotein (hnRNP) K. We showed that hnRNP K is
      required for maintaining rRNA stability: under stress conditions, eIF3f
      dissociates hnRNP K from rRNA, thereby preventing it from protecting rRNA from
      degradation. We also demonstrated that rRNA degradation occurred in non-P body,
      non-stress granule cytoplasmic foci that contain eIF3f. Our findings established
      a new mechanism of rRNA decay regulation mediated by hnRNP K/eIF3f and suggest
      that the tumor suppressive function of eIF3f may link to impaired rRNA
      degradation and translation.

PMID- 22457826
TI  - Detection of human papillomaviruses by polymerase chain reaction and ligation
      reaction on universal microarray.
AB  - Sensitive and specific detection of human papillomaviruses (HPV) in cervical
      samples is a useful tool for the early diagnosis of epithelial neoplasia and
      anogenital lesions. Recent studies support the feasibility of HPV DNA testing
      instead of cytology (Pap smear) as a primary test in population screening for
      cervical cancer. This is likely to be an option in the near future in many
      countries, and it would increase the efficiency of screening for cervical
      abnormalities. We present here a microarray test for the detection and typing of
      15 most important high-risk HPV types and two low risk types. The method is based
      on type specific multiplex PCR amplification of the L1 viral genomic region
      followed by ligation detection reaction where two specific ssDNA probes, one
      containing a fluorescent label and the other a flanking ZipCode sequence, are
      joined by enzymatic ligation in the presence of the correct HPV PCR product.
      Human beta-globin is amplified in the same reaction to control for sample quality
      and adequacy. The genotyping capacity of our approach was evaluated against
      Linear Array test using cervical samples collected in transport medium.
      Altogether 14 out of 15 valid samples (93%) gave concordant results between our
      test and Linear Array. One sample was HPV56 positive in our test and high-risk
      positive in Hybrid Capture 2 but remained negative in Linear Array. The
      preliminary results suggest that our test has accurate multiple HPV genotyping
      capability with the additional advantages of generic detection format, and
      potential for high-throughput screening.

PMID- 22457827
TI  - Expression profile of nuclear receptors along male mouse nephron segments reveals
      a link between ERRbeta and thick ascending limb function.
AB  - The nuclear receptor family orchestrates many functions related to reproduction,
      development, metabolism, and adaptation to the circadian cycle. The majority of
      these receptors are expressed in the kidney, but their exact quantitative
      localization in this ultrastructured organ remains poorly described, making it
      difficult to elucidate the renal function of these receptors. In this report,
      using quantitative PCR on microdissected mouse renal tubules, we established a
      detailed quantitative expression map of nuclear receptors along the nephron. This
      map can serve to identify nuclear receptors with specific localization. Thus, we
      unexpectedly found that the estrogen-related receptor beta (ERRbeta) is expressed
      predominantly in the thick ascending limb (TAL) and, to a much lesser extent, in
      the distal convoluted tubules. In vivo treatment with an ERR inverse agonist
      (diethylstilbestrol) showed a link between this receptor family and the
      expression of the Na+,K+-2Cl- cotransporter type 2 (NKCC2), and resulted in
      phenotype presenting some similarities with the Bartter syndrom (hypokalemia,
      urinary Na+ loss and volume contraction). Conversely, stimulation of ERRbeta with
      a selective agonist (GSK4716) in a TAL cell line stimulated NKCC2 expression. All
      together, these results provide broad information regarding the renal expression
      of all members of the nuclear receptor family and have allowed us to identify a
      new regulator of ion transport in the TAL segments.

PMID- 22457828
TI  - The rice HGW gene encodes a ubiquitin-associated (UBA) domain protein that
      regulates heading date and grain weight.
AB  - Heading date and grain weight are two determining agronomic traits of crop yield.
      To date, molecular factors controlling both heading date and grain weight have
      not been identified. Here we report the isolation of a hemizygous mutation,
      heading and grain weight (hgw), which delays heading and reduces grain weight in
      rice. Analysis of hgw mutant phenotypes indicate that the hemizygous hgw mutation
      decreases latitudinal cell number in the lemma and palea, both composing the
      spikelet hull that is known to determine the size and shape of brown grain.
      Molecular cloning and characterization of the HGW gene showed that it encodes a
      novel plant-specific ubiquitin-associated (UBA) domain protein localized in the
      cytoplasm and nucleus, and functions as a key upstream regulator to promote
      expressions of heading date- and grain weight-related genes. Moreover, co
      expression analysis in rice and Arabidopsis indicated that HGW and its
      Arabidopsis homolog are co-expressed with genes encoding various components of
      ubiquitination machinery, implying a fundamental role for the ubiquitination
      pathway in heading date and grain weight control.

PMID- 22457829
TI  - Increased gut permeability and microbiota change associate with mesenteric fat
      inflammation and metabolic dysfunction in diet-induced obese mice.
AB  - We investigated the relationship between gut health, visceral fat dysfunction and
      metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or
      high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory
      markers were measured. Proximal colon barrier function was assessed by measuring
      transepithelial resistance and mRNA expression of tight-junction proteins. Gut
      microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-6 mRNA levels were measured in proximal
      colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration
      (F4/80+) was assessed using immunohistochemical staining. HFD mice had a higher
      insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P =
      0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of
      HFD mice compared to mice fed the control diet, transepithelial resistance and
      mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P =
      0.025) respectively and TNF-alpha mRNA level was 6.6-fold higher (P = 0.037). HFD
      reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P =
      0.004) in fecal microbiota. Correlations were found between abundances of
      Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = -0.55; P = 0.007) with
      transepithelial resistance of the proximal colon. HFD increased macrophage
      infiltration (58%; P = 0.020), TNF-alpha (2.5-fold, P<0.001) and IL-6 mRNA levels
      (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in
      epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither
      TNF-alpha nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed
      no signs of inflammation in HFD mice. The current results implicate gut
      dysfunction, and attendant inflammation of contiguous adipose, as salient
      features of the metabolic dysregulation of diet-induced obesity.

PMID- 22457830
TI  - Characterization of periplasmic protein BP26 epitopes of Brucella melitensis
      reacting with murine monoclonal and sheep antibodies.
AB  - More than 35,000 new cases of human brucellosis were reported in 2010 by the
      Chinese Center for Disease Control and Prevention. An attenuated B. melitensis
      vaccine M5-90 is currently used for vaccination of sheep and goats in China. In
      the study, a periplasmic protein BP26 from M5-90 was characterized for its
      epitope reactivity with mouse monoclonal and sheep antibodies. A total of 29
      monoclonal antibodies (mAbs) against recombinant BP26 (rBP26) were produced,
      which were tested for reactivity with a panel of BP26 peptides, three truncated
      rBP26 and native BP26 containing membrane protein extracts (NMP) of B. melitensis
      M5-90 in ELISA and Western-Blot. The linear, semi-conformational and
      conformational epitopes from native BP26 were identified. Two linear epitopes
      recognized by mAbs were revealed by 28 of 16mer overlapping peptides, which were
      accurately mapped as the core motif of amino acid residues 93DRDLQTGGI101
      (position 93 to 101) or residues 104QPIYVYPD111, respectively. The reactivity of
      linear epitope peptides, rBP26 and NMP was tested with 137 sheep sera by ELISAs,
      of which the two linear epitopes had 65-70% reactivity and NMP 90% consistent
      with the results of a combination of two standard serological tests. The results
      were helpful for evaluating the reactivity of BP26 antigen in M5-90.

PMID- 22457831
TI  - Propionyl-L-carnitine corrects metabolic and cardiovascular alterations in diet
      induced obese mice and improves liver respiratory chain activity.
AB  - AIMS: Obesity is a primary contributor to acquired insulin resistance leading to
      the development of type 2 diabetes and cardiovascular alterations. The carnitine
      derivate, propionyl-L-carnitine (PLC), plays a key role in energy control. Our
      aim was to evaluate metabolic and cardiovascular effects of PLC in diet-induced
      obese mice. METHODS: C57BL/6 mice were fed a high-fat diet for 9 weeks and then
      divided into two groups, receiving either free- (vehicle-HF) or PLC-supplemented
      water (200 mg/kg/day) during 4 additional weeks. Standard diet-fed animals were
      used as lean controls (vehicle-ST). Body weight and food intake were monitored.
      Glucose and insulin tolerance tests were assessed, as well as the HOMA(IR), the
      serum lipid profile, the hepatic and muscular mitochondrial activity and the
      tissue nitric oxide (NO) liberation. Systolic blood pressure, cardiac and
      endothelial functions were also evaluated. RESULTS: Vehicle-HF displayed a
      greater increase of body weight compared to vehicle-ST that was completely
      reversed by PLC treatment without affecting food intake. PLC improved the insulin
      resistant state and reversed the increased total cholesterol but not the increase
      in free fatty acid, triglyceride and HDL/LDL ratio induced by high-fat diet.
      Vehicle-HF exhibited a reduced cardiac output/body weight ratio, endothelial
      dysfunction and tissue decrease of NO production, all of them being improved by
      PLC treatment. Finally, the decrease of hepatic mitochondrial activity by high
      fat diet was reversed by PLC. CONCLUSIONS: Oral administration of PLC improves
      the insulin-resistant state developed by obese animals and decreases the
      cardiovascular risk associated to this metabolic alteration probably via
      correction of mitochondrial function.

PMID- 22457832
TI  - Virulence potential and genomic mapping of the worldwide clone Escherichia coli
      ST131.
AB  - Recently, the worldwide propagation of clonal CTX-M-15-producing Escherichia coli
      isolates, namely ST131 and O25b:H4, has been reported. Like the majority of extra
      intestinal pathogenic E. coli isolates, the pandemic clone ST131 belongs to
      phylogenetic group B2, and has recently been shown to be highly virulent in a
      mouse model, even though it lacks several genes encoding key virulence factors
      (Pap, Cnf1 and HlyA). Using two animal models, Caenorhabditis elegans and
      zebrafish embryos, we assessed the virulence of three E. coli ST131 strains (2
      CTX-M-15- producing urine and 1 non-ESBL-producing faecal isolate), comparing
      them with five non-ST131 B2 and a group A uropathogenic E. coli (UPEC). In C.
      elegans, the three ST131 strains showed intermediate virulence between the non
      virulent group A isolate and the virulent non-ST131 B2 strains. In zebrafish, the
      CTX-M-15-producing ST131 UPEC isolates were also less virulent than the non-ST131
      B2 strains, suggesting that the production of CTX-M-15 is not correlated with
      enhanced virulence. Amongst the non-ST131 B2 group isolates, variation in
      pathogenic potential in zebrafish embryos was observed ranging from intermediate
      to highly virulent. Interestingly, the ST131 strains were equally persistent in
      surviving embryos as the non-ST131-group B2 strains, suggesting similar
      mechanisms may account for development of persistent infection. Optical maps of
      the genome of the ST131 strains were compared with those of 24 reference E. coli
      strains. Although small differences were seen within the ST131 strains, the tree
      built on the optical maps showed that these strains belonged to a specific
      cluster (86% similarity) with only 45% similarity with the other group B2 strains
      and 25% with strains of group A and D. Thus, the ST131 clone has a genetic
      composition that differs from other group B2 strains, and appears to be less
      virulent than previously suspected.

PMID- 22457833
TI  - Rational design and characterization of D-Phe-Pro-D-Arg-derived direct thrombin
      inhibitors.
AB  - The tremendous social and economic impact of thrombotic disorders, together with
      the considerable risks associated to the currently available therapies, prompt
      for the development of more efficient and safer anticoagulants. Novel peptide
      based thrombin inhibitors were identified using in silico structure-based design
      and further validated in vitro. The best candidate compounds contained both L-
      and D-amino acids, with the general sequence D-Phe(P3)-Pro(P2)-D-Arg(P1)-P1'
      CONH2. The P1' position was scanned with L- and D-isomers of natural or unnatural
      amino acids, covering the major chemical classes. The most potent non-covalent
      and proteolysis-resistant inhibitors contain small hydrophobic or polar amino
      acids (Gly, Ala, Ser, Cys, Thr) at the P1' position. The lead tetrapeptide, D-Phe
      Pro-D-Arg-D-Thr-CONH2, competitively inhibits alpha-thrombin's cleavage of the
      S2238 chromogenic substrate with a K(i) of 0.92 uM. In order to understand the
      molecular details of their inhibitory action, the three-dimensional structure of
      three peptides (with P1' L-isoleucine (fPrI), L-cysteine (fPrC) or D-threonine
      (fPrt)) in complex with human alpha-thrombin were determined by X-ray
      crystallography. All the inhibitors bind in a substrate-like orientation to the
      active site of the enzyme. The contacts established between the D-Arg residue in
      position P1 and thrombin are similar to those observed for the L-isomer in other
      substrates and inhibitors. However, fPrC and fPrt disrupt the active site His57
      Ser195 hydrogen bond, while the combination of a P1 D-Arg and a bulkier P1'
      residue in fPrI induce an unfavorable geometry for the nucleophilic attack of the
      scissile bond by the catalytic serine. The experimental models explain the
      observed relative potency of the inhibitors, as well as their stability to
      proteolysis. Moreover, the newly identified direct thrombin inhibitors provide a
      novel pharmacophore platform for developing antithrombotic agents by exploring
      the conformational constrains imposed by the D-stereochemistry of the residues at
      positions P1 and P1'.

PMID- 22457834
TI  - Host differences in influenza-specific CD4 T cell and B cell responses are
      modulated by viral strain and route of immunization.
AB  - The antibody response to influenza infection is largely dependent on CD4 T cell
      help for B cells. Cognate signals and secreted factors provided by CD4 T cells
      drive B cell activation and regulate antibody isotype switching for optimal
      antiviral activity. Recently, we analyzed HLA-DR1 transgenic (DR1) mice and
      C57BL/10 (B10) mice after infection with influenza virus A/New Caledonia/20/99
      (NC) and defined epitopes recognized by virus-specific CD4 T cells. Using this
      information in the current study, we demonstrate that the pattern of secretion of
      IL-2, IFN-gamma, and IL-4 by CD4 T cells activated by NC infection is largely
      independent of epitope specificity and the magnitude of the epitope-specific
      response. Interestingly, however, the characteristics of the virus-specific CD4 T
      cell and the B cell response to NC infection differed in DR1 and B10 mice. The
      response in B10 mice featured predominantly IFN-gamma-secreting CD4 T cells and
      strong IgG2b/IgG2c production. In contrast, in DR1 mice most CD4 T cells secreted
      IL-2 and IgG production was IgG1-biased. Infection of DR1 mice with influenza PR8
      generated a response that was comparable to that in B10 mice, with predominantly
      IFN-gamma-secreting CD4 T cells and greater numbers of IgG2c than IgG1 antibody
      secreting cells. The response to intramuscular vaccination with inactivated NC
      was similar in DR1 and B10 mice; the majority of CD4 T cells secreted IL-2 and
      most IgG antibody-secreting cells produced IgG2b or IgG2c. Our findings identify
      inherent host influences on characteristics of the virus-specific CD4 T cell and
      B cell responses that are restricted to the lung environment. Furthermore, we
      show that these host influences are substantially modulated by the type of
      infecting virus via the early induction of innate factors. Our findings emphasize
      the importance of immunization strategy for demonstrating inherent host
      differences in CD4 T cell and B cell responses.

PMID- 22457836
TI  - In vitro study of transverse strength of fiber reinforced composites.
AB  - OBJECTIVE: Reinforcement with fiber is an effective method for considerable
      improvement in flexural properties of indirect composite resin restorations. The
      aim of this in-vitro study was to compare the transverse strength of composite
      resin bars reinforced with pre-impregnated and non-impregnated fibers. MATERIALS
      AND METHODS: Thirty six bar type composite resin specimens (3*2*25 mm) were
      constructed in three groups. The first group was the control group (C) without
      any fiber reinforcement. The specimens in the second group (P) were reinforced
      with pre-impregnated fibers and the third group (N) with non-impregnated fibers.
      These specimens were tested by the three-point bending method to measure primary
      transverse strength. Data were statistically analyzed with one way ANOVA and
      Tukey's tests. RESULTS: There was a significant difference among the mean primary
      transverse strength in the three groups (P<0.001). The post-hoc (Tukey) test
      showed that there was a significant difference between the pre-impregnated and
      control groups in their primary transverse strength (P<0.001). Regarding
      deflection, there was also a significant difference among the three groups
      (P=0.001). There were significant differences among the mean deflection of the
      control group and two other groups (P(C&N)<.001 and P(C&P)=.004), but there was
      no significant difference between the non-and pre-impregnated groups
      (P(N&P)=.813). CONCLUSION: Within the limitations of this study, it was concluded
      that reinforcement with fiber considerably increased the transverse strength of
      composite resin specimens, but impregnation of the fiber used implemented no
      significant difference in the transverse strength of composite resin samples.

PMID- 22457835
TI  - Next generation sequencing for profiling expression of miRNAs: technical progress
      and applications in drug development.
AB  - miRNAs are non-coding RNAs that play a regulatory role in expression of genes and
      are associated with diseases. Quantitatively measuring expression levels of
      miRNAs can help in understanding the mechanisms of human diseases and discovering
      new drug targets. There are three major methods that have been used to measure
      the expression levels of miRNAs: real-time reverse transcription PCR (qRT-PCR),
      microarray, and the newly introduced next-generation sequencing (NGS). NGS is not
      only suitable for profiling of known miRNAs as qRT-PCR and microarray can do too
      but it also is able to detect unknown miRNAs which the other two methods are
      incapable of doing. Profiling of miRNAs by NGS has progressed rapidly and is a
      promising field for applications in drug development. This paper reviews the
      technical advancement of NGS for profiling miRNAs, including comparative analyses
      between different platforms and software packages for analyzing NGS data.
      Examples and future perspectives of applications of NGS profiling miRNAs in drug
      development will be discussed.

PMID- 22457837
TI  - Fabrication and evaluation of a noncompliant molar distalizing appliance: bonded
      molar distalizer.
AB  - OBJECTIVE: Attempts to treat class II malocclusions without extraction in non
      compliant patients have led to utilization of intraoral molar distalizing
      appliances. The purpose of this study was to investigate dental and skeletal
      effects of Bonded Molar Distalizer (BMD) which is a simple molar distalizing
      appliance. MATERIALS AND METHODS: Sixteen patients (12 girls, four boys) with
      bilateral half-cusp class II molar relationship, erupted permanent second molars
      and normal or vertical growth pattern were selected for bilateral distalization
      of maxillary molars via BMD. The screws were activated every other day,
      alternately. Lateral cephalograms and study models were obtained before treatment
      and after 11 weeks activation of the appliance. RESULTS: Significant amounts of
      molar distalization, molar distal tipping and anchorage loss were observed. The
      mean maxillary first molar distal movement was 1.22+/-0.936 mm with a distal
      tipping of 2.97+/-3.74 degrees in 11 weeks. The rate of distal movement was 0.48
      mm per month. Reciprocal mesial movement of the first premolars was 2.26+/-1.12
      mm with a mesial tipping of 4.25+/-3.12 degrees. Maxillary incisors moved 3.55+/
      1.46 mm and tipped 9.87+/-5.03 degrees mesially. Lower anterior face height
      (LAFH) decreased 1.28+/-1.36 mm. CONCLUSION: BMD is appropriate for distalizing
      maxillary molars, especially in patients with critical LAFH, although significant
      amounts of anchorage loss occur using this appliance.

PMID- 22457838
TI  - Primary school teachers' knowledge regarding emergency management of avulsed
      permanent incisors.
AB  - OBJECTIVE: The goal of this study was to evaluate primary school teachers'
      knowledge regarding emergency management of avulsed permanent incisors. MATERIALS
      AND METHODS: The study was conducted in fifty randomly chosen primary schools
      from Casablanca, Morocco. All teachers of the selected schools were included in
      the study. The data were collected by self administered questionnaires. The
      questions focused on the teachers' general characteristics, experience of avulsed
      teeth and the importance of emergency management. The data were analyzed using
      chi square test. RESULTS: A total of 501 teachers, of which 23.6% were male and
      75.4% were female, answered the questionnaire. The results showed that 44.5 % of
      the teachers had an experience of avulsed tooth at school, 82.82% of them knew
      the importance of emergency management and 32.6% would look for a dentist for
      treatment of the cases. Only 15.8% would reimplant the tooth themselves.
      Regarding the storage media, 21.95% would keep the avulsed tooth in milk. There
      was no significant difference between gender and education level (p>0.05).
      CONCLUSION: This study shows school teachers' lack of knowledge regarding dental
      trauma and especially tooth avulsion. Therefore, the results indicated that
      educational programs are necessary for improvement in their level of knowledge.

PMID- 22457839
TI  - The effect of preparation design on the fracture resistance of zirconia crown
      copings (computer associated design/computer associated machine, CAD/CAM system).
AB  - OBJECTIVE: One of the major problems of all ceramic restorations is their
      probable fracture against the occlusal force. The aim of the present in-vitro
      study is was to compare the effect of two marginal designs (chamfer & shoulder)
      on the fracture resistance of zirconia copings, CERCON (CAD/CAM). MATERIALS AND
      METHODS: This in vitro study was done with single blind experimental technique.
      One stainless steel dye with 50' chamfer finish line design (0.8 mm depth) was
      prepared using milling machine. Ten epoxy resin dyes were made, The same dye was
      retrieved and 50' chamfer was converted into shoulder (1 mm).again ten epoxy
      resin dyes were made from shoulder dyes. Zirconia cores with 0.4 mm thickness and
      35 MUm cement Space fabricated on the 20 epoxy resin dyes (10 samples chamfer and
      10 samples shoulder) in a dental laboratory. Then the zirconia cores were
      cemented on the epoxy resin dyes and underwent a fracture test with a universal
      testing machine (GOTECH AI-700LAC, Arson, USA) and samples were investigated from
      the point of view of the origin of the failure. RESULT: The mean value of
      fracture resistance for shoulder margins were 788.90+/-99.56 N and for the
      chamfer margins were 991.75+/-112.00 N. The student's T-test revealed a
      statistically significant difference between groups (P=0.001). CONCLUSION: The
      result of this study indicates that marginal design of the zirconia cores effects
      on their fracture resistance. A chamfer margin could improve the biomechanical
      performance of posterior single zirconia crown restorations. This may be because
      of strong unity and round internal angle in chamfer margin.

PMID- 22457840
TI  - Comparison of peri-implant bone loss and survival of maxillary intrasinus and
      extrasinus implants after 2 years.
AB  - OBJECTIVE: Low quality of the bone and insufficient bone due to the size of the
      sinus and resorption of the alveolar ridge decrease the long-term survival of
      implants in the posterior maxilla compared to other regions of the jaws. Surgical
      procedures to increase bone volume make it possible to place implants longer than
      8 mm. In this situation sinus elevation makes it possible to place implants. We
      intend to evaluate peri-implant bone loss and survival of implants placed in
      elevated sinuses after 2 years and to compare with implants placed in the native
      posterior maxilla. MATERIALS AND METHODS: Twenty-five implants placed in sinuses
      that had been reconstructed with Bio-Oss and healed after 9 months were compared
      with 30 implants placed in the posterior maxilla without any surgery. The groups
      were compared using probing pocket depth, bleeding on probing, Plaque Index and
      bone loss immediately after implant placement surgery and 2 years
      postoperatively. The criterion for implant survival was presence or absence of
      the implant in the oral cavity, which was recorded in relevant forms in both
      groups. RESULTS: Three implants were lost; one in control and two in grafted
      sinuses. No significant differences were observed in the survival rates. In
      general, the mean bone loss around intrasinus and extrasinus implants was not
      significantly different. In the same context, no differences were observed
      between bleeding on probing, Plaque Index and probing pocket depths of two groups
      (P=0.397, P=0.637 and P=0.224, respectively). CONCLUSION: The survival and bone
      loss around intrasinus and extrasinus implants are similar.

PMID- 22457841
TI  - In vitro color change of three dental veneering resins in tea, coffee and
      tamarind extracts.
AB  - OBJECTIVE: To study the in vitro color changes of three dental resin veneering
      materials when immersed in tea, coffee and tamarind extracts. MATERIALS AND
      METHODS: The color changes of heat polymerized tooth colored acrylic resin
      (Stellondetrey, B, F14, DPI Dental products of India Ltd, Mumbai), auto
      polymerized tooth colored acrylic resin (DPI, B, QV5, DPI Dental products of
      India Ltd, Mumbai) and light polymerized resin composite (Herculite XRV, Enamel
      A2, part no. 22860, lot no. 910437, Kerr Corporation, West Collins Avenue,
      Orange, CA, USA) when immersed in water extracts of tea (Tata Tea Ltd. Bangalore,
      India), coffee (Tata Coffee Ltd. Coorg, India) and tamarind were evaluated using
      computer vision systems. The color images were recorded in R (red), G (green) and
      B (blue) form and converted into H (hue), S (saturation) and V (value). RESULTS:
      Significant color change occurred for auto polymerized tooth colored acrylic
      resin in tamarind extract, for heat polymerized tooth colored acrylic resin in
      tea extract and for light polymerized resin composite in coffee extract. Auto
      polymerized tooth colored acrylic resin samples showed an overall higher color
      change. However, for all the material samples coffee extract produced more color
      change. CONCLUSION: These results suggest that the color stability of the resins
      is influenced by the presence of secondary metabolites such as tartaric acid,
      tannins, caffeine, saponins and phenols in tamarind, tea and coffee extracts.

PMID- 22457842
TI  - Oro-dental health status and salivary characteristics in children with chronic
      renal failure.
AB  - Children suffering from decreased renal function may demand unique considerations
      regarding special oral and dental conditions they are encountered to. It is
      mentioned that renal function deterioration may affect the hard or soft tissues
      of the mouth. Having knowledge about the high prevalence of dental defects,
      calculus, gingival hyperplasia, modified salivary composition and tissue
      responses to the dental plaque may aid the physician and the dentist to help
      nurture the patient with chronic renal failure through the crisis, with an
      aesthetically satisfying and functioning dentition.

PMID- 22457843
TI  - Spontaneous regeneration of the mandible after hemimandibulectomy: report of a
      case.
AB  - Mandibular defects may result from many conditions such as trauma, inflammatory
      diseases and tumors. There are rare cases reported in the literature that have
      demonstrated spontaneous bone regeneration after resection of the mandible.
      Several factors such as age, preservation of the periosteum and genetics seem to
      influence spontaneous bone regeneration capacity in individuals. Evaluation of
      these factors may lead to a better understanding of the mechanism of spontaneous
      bone regeneration and also help to create new methods for bone reconstruction.
      The purpose of this article was to describe the spontaneous regeneration of the
      hemi-mandible with a well shaped condyle and coronoid after resecting a
      mandibular pathologic lesion in a young man.

PMID- 22457844
TI  - Heritability Estimation using Regression Models for Correlation.
AB  - Heritability estimates a polygenic effect on a trait for a population. Reliable
      interpretation of heritability is critical in planning further genetic studies to
      locate a gene responsible for the trait. This study accommodates both single and
      multiple trait cases by employing regression models for correlation parameter to
      infer the heritability. Sharing the properties of regression approach, the
      proposed methods are exible to incorporate non-genetic and/or non-additive
      genetic information in the analysis. The performances of the proposed model are
      compared with those using the likelihood approach through simulations and carotid
      Intima Media Thickness analysis from Northern Manhattan family Study.

PMID- 22307216
TI  - Pharmacokinetics of memantine in rats and mice.
AB  - To evaluate the potential of memantine as a therapeutic agent for Huntington's
      disease (HD) we have undertaken a series of in vitro, ex vivo and whole animal
      studies to characterize its pharmacokinetics (PK) and pharmacodynamics (PD) in
      rats and mice. Results from these studies will enable determination of memantine
      exposures needed to engage the related functional PD marker and help predict the
      dose regimen for clinical trials to test its proposed mechanism of action; the
      selective blockade of extrasynaptic, but not synaptic, NMDA receptors. The
      studies reported here describe the PK of memantine in rats and mice at low (1
      mg/kg) and high (10 mg/kg) doses. Our studies indicate that the clearance
      mechanisms of memantine in rats and mice are different from those in human, and
      that clearance needs to be taken into account when extrapolating to the human. In
      rats only, there is a significant metabolic contribution to memantine clearance
      at lower dose levels. While memantine is primarily cleared renally in all three
      species, the proportion of total systemic clearance above the glomerular
      filtration rate (GFR) is much higher in rats and mice (~13, 4.5, and 1.4 times
      higher than GFR in rats, mice, and humans, respectively), suggesting that the
      contribution of active transport to memantine elimination in rats and mice is
      more significant than in the human. In rats and mice, memantine had a short half
      life (<4 h) and steep Cmax/Cmin ratios (>100). In the human, the half-life of
      memantine was reported to be very long (60-80 h) with a Cmax/Cmin ratio at steady
      state concentrations of ~1.5. A small change in the clearance of memantine - for
      example due to renal impairment or competition for the elimination pathway with a
      co-administered drug - will likely affect exposure and, therefore, the
      selectivity of memantine on NMDA receptors . The PK differences observed between
      these species demonstrate that the PK in mice and rats cannot be directly
      extrapolated to the human. Further, the relationship between the plasma
      concentration (and therefore dose) needed to elicit a mechanism-related in vivo
      functional effect (PD readout) while maintaining the selectivity of the
      extrasynaptic blockade of the NMDA receptors needs to be established before
      clinical trials can be appropriately planned.

PMID- 22307262
TI  - Stability effects on results of diffusion tensor imaging analysis by reduction of
      the number of gradient directions due to motion artifacts: an application to
      presymptomatic Huntington's disease.
AB  - In diffusion tensor imaging (DTI), an improvement in the signal-to-noise ratio
      (SNR) of the fractional anisotropy (FA) maps can be obtained when the number of
      recorded gradient directions (GD) is increased. Vice versa, elimination of motion
      corrupted or noisy GD leads to a more accurate characterization of the diffusion
      tensor. We previously suggest a slice-wise method for artifact detection in FA
      maps. This current study applies this approach to a cohort of 18 premanifest
      Huntington's disease (pHD) subjects and 23 controls. By 2-D voxelwise statistical
      comparison of original FA-maps and FA-maps with a reduced number of GD, the
      effect of eliminating GD that were affected by motion was demonstrated.We present
      an evaluation metric that allows to test if the computed FA-maps (with a reduced
      number of GD) still reflect a "true" FA-map, as defined by simulations in the
      control sample. Furthermore, we investigated if omitting data volumes affected by
      motion in the pHD cohort could lead to an increased SNR in the resulting FA
      maps.A high agreement between original FA maps (with all GD) and corrected FA
      maps (i.e. without GD corrupted by motion) were observed even for numbers of
      eliminated GD up to 13. Even in one data set in which 46 GD had to be eliminated,
      the results showed a moderate agreement.

PMID- 22457847
TI  - Voluntary wheel running in dystrophin-deficient (mdx) mice: Relationships between
      exercise parameters and exacerbation of the dystrophic phenotype.
AB  - Voluntary wheel running can potentially be used to exacerbate the disease
      phenotype in dystrophin-deficient mdx mice. While it has been established that
      voluntary wheel running is highly variable between individuals, the key
      parameters of wheel running that impact the most on muscle pathology have not
      been examined in detail. We conducted a 2-week test of voluntary wheel running by
      mdx mice and the impact of wheel running on disease pathology. There was
      significant individual variation in the average daily distance (ranging from
      0.003 +/- 0.005 km to 4.48 +/- 0.96 km), culminating in a wide range (0.040 km to
      67.24 km) of total cumulative distances run by individuals. There was also
      variation in the number and length of run/rest cycles per night, and the average
      running rate. Correlation analyses demonstrated that in the quadriceps muscle, a
      low number of high distance run/rest cycles was the most consistent indicator for
      increased tissue damage. The amount of rest time between running bouts was a key
      factor associated with gastrocnemius damage. These data emphasize the need for
      detailed analysis of individual running performance, consideration of the length
      of wheel exposure time, and the selection of appropriate muscle groups for
      analysis, when applying the use of voluntary wheel running to disease
      exacerbation and/or pre-clinical testing of the efficacy of therapeutic agents in
      the mdx mouse.

PMID- 22307361
TI  - Aspiration pneumonia and death in Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurodegenerative autosomal dominant
      disease characterized by choreatic and hypokinetic movements, disturbed
      behaviour, and cognitive decline. Pneumonia is the most common cause of death,
      followed by cardiovasculair diseases. It has been suggested that choking is the
      causative underlying factor for pneumonia in HD. As a detailed specification of
      the type of pneumonia has never been performed, we analyzed the records of our
      Brain Bank containing 224 cases to determine the exact cause of death and type of
      pneumonia. The conclusion is that the majority (86.8%) of our HD patients where
      the cause of death could be identified died from aspiration pneumonia.

PMID- 22306689
TI  - Percent-predicted 6-minute walk distance in duchenne muscular dystrophy to
      account for maturational influences.
AB  - We recently described a modified version of the 6-minute walk test (6MWT) for
      Duchenne muscular dystrophy (DMD) based partly on the American Thoracic Society
      (ATS) guidelines. This measure has shown reliability, validity and utility as a
      primary outcome measure in DMD clinical trials. Because loss of muscle function
      in DMD occurs against the background of normal childhood growth and development,
      younger children with DMD can show increase in distance walked during 6MWT over
      ~1 year despite progressive muscular impairment. In this study, we compare 6
      minute walk distance (6MWD) data from DMD boys (n=17) and typically developing
      control subjects (n=22) to existing normative data from age- and sex-matched
      children and adolescents. An age- and height-based equation fitted to normative
      data by Geiger and colleagues was used to convert 6MWD to a percent-predicted (%
      predicted) value in boys with DMD. Analysis of %-predicted 6MWD data represents a
      method to account for normal growth and development, and shows that gains in
      function at early ages represents stable rather than improving abilities in boys
      with DMD. Boys with DMD from 4-7 years of age maintain a stable 6MWD
      approximately 80% of that of typically developing peers, with the deficit
      progressing at a variable rate thereafter.

PMID- 22457851
TI  - Predecidualized endometriosis presenting as rectosigmoid polyps with stenosis.

PMID- 22367358
TI  - Dysferlin-deficient immortalized human myoblasts and myotubes as a useful tool to
      study dysferlinopathy.
AB  - Dysferlin gene mutations causing LGMD2B are associated with defects in muscle
      membrane repair. Four stable cell lines have been established from primary human
      dysferlin-deficient myoblasts harbouring different mutations in the dysferlin
      gene. We have compared immortalized human myoblasts and myotubes carrying disease
      causing mutations in dysferlin to their wild-type counterparts. Fusion of
      myoblasts into myotubes and expression of muscle-specific differentiation markers
      were investigated with special emphasis on dysferlin protein expression,
      subcellular localization and function in membrane repair. We found that the
      immortalized myoblasts and myotubes were virtually indistinguishable from their
      parental cell line for all of the criteria we investigated. They therefore will
      provide a very useful tool to further investigate dysferlin function and
      pathophysiology as well as to test therapeutic strategies at the cellular level.

PMID- 22457852
TI  - Ischemic gastropathy.

PMID- 22457853
TI  - Cat scratch colon during tumor observation prior to endoscopic treatment.

PMID- 22457854
TI  - Patients with coeliac disease are increasingly overweight or obese on
      presentation.
AB  - BACKGROUND: Historically weight loss is a classic symptom of Coeliac Disease
      (CD). Recent studies suggest CD sufferers are significantly more likely to be
      obese or underweight at the time of presentation. This study aimed to establish
      the frequency of obesity in newly diagnosed Coeliac Disease (CD). METHODS:
      Dietetic records of CD patients were reviewed and patient demographics, initial
      assessment date, and Body Mass Index (BMI) recorded and statistically analysed.
      RESULTS: out of 187 CD patients diagnosed between 1999 and 2009, 127 patients
      were female (68%) and 60 male (32%) (ratio 2:1). Overall median age was 54 years
      (range 18 to 87). Median BMI was 23.6, inter-quartile range (IQR) 21.5 - 28.1.
      Male median BMI was 23.9, IQR 21.8 - 27.3. Female median BMI was 23.2, IQR 21.4 -
      28.6. Overall 83 patients (44%) had a BMI of 25 or above. No significant
      difference was found in the proportion of patients with a BMI of 25 or above when
      compared according to gender, age or year of referral. Twenty-five patients (13
      %) had a BMI of 30 or above. Twenty were female with a median age of 56 years
      (range 18 - 71). The proportion of females with a BMI of 30 or more was 11%
      compared with only 3% males (ratio 5:1). Only 5 patients (3%) had a BMI less than
      18.5. CONCLUSION: A significant proportion of CD patients (close to half of
      patients) were diagnosed with a BMI of 25 or over. Compared to males, females
      have a wider range of BMI and more likely to be obese (BMI of 30 or more).

PMID- 22457855
TI  - Patients' experiences and perceptions of living with coeliac disease -
      implications for optimizing care.
AB  - BACKGROUND AND AIMS: Little is known regarding the impact of coeliac disease on
      daily living from patients' own viewpoints. The aim of the study was to
      investigate patients' perceptions of their disease, dietary treatment and self
      rated healthcare needs. METHODS: This prospective study involved 698 newly
      detected adult coeliac disease patients diagnosed due to classical abdominal
      symptoms, extraintestinal symptoms or active screening in at-risk groups.
      Participants were asked about their experiences of living with coeliac disease
      and of adopting a gluten-free diet, as well as their disease-related needs at
      diagnosis and after one year on treatment. RESULTS: All patients were equally
      satisfied that they had been diagnosed with coeliac disease irrespective of
      initial clinical presentation. However, young patients and those with
      extraintestinal symptoms or asymptomatic and detected by screening in at-risk
      groups rated the impact on daily living of the disease and adherence to a gluten
      free diet with significantly more disapproval than those with classical symptoms.
      The former groups clarify also reported dietary lapses and a negative attitude to
      the disease more frequently. Negative perceptions were associated with
      dissatisfaction with the quality of doctor-patient communication and younger age
      at diagnosis. CONCLUSIONS: Established doctor-patient communication is essential
      in minimizing the disease burden. Particularly young and screen-detected
      asymptomatic patients and those with extraintestinal manifestations require
      extensive support.

PMID- 22457856
TI  - IL-6 and IL-11 as markers for tumor aggressiveness and prognosis in gastric
      adenocarcinoma patients without mutations in Gp130 subunits.
AB  - BACKGROUND AND AIMS: A point mutation (gp130Y757F/Y759F) was identified as being
      responsible for aberrant activation of gp130 in mice and associated with gastric
      adenocarcinoma induction. As a result, we investigated the possible role of key
      point mutations in Tyr from IL6ST exon 17 that encode for the catalytic domain of
      gp130, and of its respective activators (IL-6 family member cytokines) in human
      gastric cancer initiation and development. METHOD: DNA, protein and plasma from
      51 patients with gastric adenocarcinoma have been used in exploring gp130 status.
      We used sequencing analysis of IL6ST exon 17 in order to identify possible
      mutations that would lead to constitutive active forms of the receptor. The
      levels of gp130 activators (IL-6, IL-11, LIF) were analyzed by ELISA in plasma
      and mucosa of patients with gastric adenocarcinoma. RESULTS: Sequencing analysis
      did not identify mutations in gp130 key positions (Y759, Y767, Y814, Y905 and
      Y915). An increased IL-6 and IL-11 level in gastric mucosa was observed,
      correlated with staging, indicating these cytokines as gp130 activators in tumor
      epithelial cell. Those variations were consistent with increased IL-6 level in
      plasma. Furthermore, IL-6, but not IL-11 showed a significant correlation with
      patient's survival time, suggesting that tissue and plasma concentration of IL-6
      might be a marker of tumor aggressiveness with prognostic value. CONCLUSIONS:
      According to our results, no mutations were detected in gp130 key positions in
      human gastric adenocarcinoma samples. However, gp130 activation may occur due to
      the increased level of IL-6 and IL-11 cytokines detected that can become valuable
      biomarkers.

PMID- 22457857
TI  - Serotonin transporter gene (SLC6A4) polymorphism in patients with irritable bowel
      syndrome and healthy controls.
AB  - BACKGROUND: Polymorphisms in serotonin re-uptake transporter (SERT or SLC6A4)
      gene may play role in disturbance in gut function in irritable bowel syndrome
      (IBS). The aim of this study was to evaluate the association between SLC6A4
      polymorphism of SERT-P and serotonin (5-hydroxytryptamine, 5-HT) concentration in
      IBS as compared with controls. METHODS: 150 patients with IBS (Rome-III criteria)
      and 252 controls were subjected to SLC6A4 genotyping. 5-HT was measured in the
      rectal biopsy of patients only. RESULTS: Patients and controls were age and
      gender-matched. Patients were classified into D-IBS: 79 (52%), C-IBS: 52 (35%)
      and A-IBS: 19 (13%). SLC6A4 polymorphism differed in IBS and controls [genotypes
      s/s, 89 (59%), l/s, 44 (29%), and l/l, 17 (12%) vs. s/s, 92 (37%), l/s, 114
      (45%), and l/l, 46 (18%), p<0.001]. SLC6A4 s/s genotype was commoner in D-IBS
      than C-IBS, A-IBS and controls (p<0.001). 5-HT level was higher in D-IBS than A
      IBS and C-IBS (154.7+/-37.1 vs. 112.4+/-24.6 vs. 104.3+/-23.7-pmol/mL, p<0.001)
      and in s/s than l/s and l/l genotypes (151.1+/-37.3 vs. 105.0+/-20.9 vs. 100.9+/
      28.0-pmol/mL, p<0.001). IBS with s/s genotype more often had abdominal pain than
      l/s and l/l [78/89 (87.6%) vs. 19/44 (43%) vs. 5/17 (29%), p<0.001]. 5-HT level
      was higher among IBS patients with abdominal pain and diarrhea than without
      (142.9+/-39.4 vs. 108.4+/-28.9-pmol/mL, p<0.001) and (140.2+/-41.3-pmol/mL vs.
      121.3+/-35.0-pmol/mL, p=0.003). CONCLUSION: The frequency of SLC6A4-polymorphism
      and higher levels of 5-HT were significantly associated with IBS, particularly in
      patients with diarrhea and abdominal pain, suggesting that SLC6A4 is a potential
      candidate gene involved in the pathogenesis of IBS.

PMID- 22457859
TI  - Single nucleotide polymorphisms in colorectal cancer: associations with tumor
      site and TNM stage.
AB  - BACKGROUND AND AIM: Colon tumor carcinogenesis and rectal tumor carcinogenesis
      have each been associated with different genetic features, but data are still
      controversial and are insufficient to support their distinct molecular biology.
      Recently, genome-wide association studies (GWAS) have also found heterogeneity in
      colorectal cancer (CRC) risks based on population ethnicity and tumor features.
      Several single nucleotide polymorphism (SNP) markers are described in the
      literature as having site and/or stage specificity, including rs10795668,
      rs3802842, rs6983267, and rs4939827. Replication of initial findings in different
      ethnic groups by independent studies is required to unravel the population
      specific differences in risk. METHODS: We examined whether inherited risk
      variants at rs10795668, rs3802842, rs6983267, and rs4939827 exerted a
      differential effect on colon and rectal cancers in a Romanian hospital based
      series of 153 CRC cases and 182 non-affected control subjects prospectively
      recruited between 2007 and 2010. RESULTS: Rectal tumors were significantly
      associated with rs4939827 (OR = 4.85, P = 0.002) and rs6983267 (OR = 3.00, P =
      0.036), suggesting that carriers of risk alleles at these loci had increased
      susceptibility to development of rectal cancer rather than colon cancer. Carrying
      the C allele at rs3802842 appeared to be associated with a lower risk for rectal
      tumors in our dataset. We found no association between genotypes and tumor
      aggressiveness as reflected by TNM staging. CONCLUSIONS: The associations between
      SNPs, and tumor site and staging remain to be further clarified. Our results
      should be considered cautiously, but may be taken into account in future, larger
      epidemiological studies.

PMID- 22457858
TI  - Higher titers of anti-Saccharomyces cerevisiae antibodies IgA and IgG are
      associated with more aggressive phenotypes in Romanian patients with Crohn's
      disease.
AB  - BACKGROUND AND AIMS: Serological markers have been widely used for diagnostic
      purposes and disease stratification in inflammatory bowel diseases (IBD). The aim
      of this study was to investigate the seroprevalence and the correlations of anti
      Saccharomyces cerevisiae antibodies (ASCA) titers with different clinical
      phenotypes in Romanian patients with Crohn's disease (CD). METHODS: The study
      included 107 CD and 86 ulcerative colitis (UC) patients from the Gastroenterology
      Departments of three University Hospitals, and 60 healthy subjects. ASCA IgA and
      IgG titers were determined using ELISA test. For CD patients the phenotype was
      established according to the Montreal classification. The differences in ASCA
      titers for different CD phenotypes were assessed using the Mann-Whitney U test.
      RESULTS: ASCA prevalence was 33.6% in CD group, 12.8% in UC group and 6.6% in the
      control group. Significantly higher IgA (p=0.05) and IgG (p=0.03) titers were
      found in patients from the Montreal A1+A2 groups (age at onset below 40) compared
      with the older patients (A3). Higher titers were found in patients with extensive
      ileo-colonic lesions (L3) and upper gastrointestinal tract involvement (L4) than
      in patients having only colonic disease (L2). Significantly higher IgA (p=0.03)
      and IgG (p=0.03) titers were observed in patients with stenosing (B2) and
      penetrating (B3) disease compared with the nonstricturing, nonpenetrating (B1)
      phenotype. No correlation between ASCA titers and disease duration was found.
      CONCLUSION: ASCA seropositivity in Romanian CD patients is lower than in Western
      Europe. Higher ASCA IgA and IgG titers are associated with a younger age at
      diagnosis and more aggressive phenotypes.

PMID- 22457860
TI  - Serum ferritin levels do not predict the stage of underlying non-alcoholic fatty
      liver disease.
AB  - BACKGROUND AND AIM: Hepatic endothelial cells release ferritin in response to
      increased oxidative stress and lipid peroxidation. The principal aim of this
      study was to determine if serum ferritin levels predict the underlying stage of
      non-alcoholic fatty liver disease (NAFLD). METHODS: The clinical, biochemical,
      radiologic and histologic findings of consecutive adult NAFLD patients accessed
      at a tertiary care center over a 15-year period were analyzed. Those with
      concurrent liver diseases were excluded. Patients were stratified into three
      groups based on their histologic stage of disease: simple steatosis, non
      alcoholic steatohepatitis (NASH) or cirrhosis. Analysis of Variance and Tukey
      Kramer Multiple Comparison tests were used to assess the relationship between
      serum ferritin levels and stages of NAFLD. RESULTS: 482 patients fulfilled
      inclusion criteria, including 60 subjects with biopsy proven simple steatosis, 28
      subjects with steatohepatitis (NASH) and 20 subjects with histologic or
      radiologic evidence of cirrhosis. Mean serum ferritin levels were similar in all
      three groups (simple steatosis: 223.9 ug/L; NASH: 240.7 ug/L; cirrhosis: 271.3
      ug/L; p=0.84). NAFLD-induced cirrhotic patients were significantly older, more
      often diabetic and hypertensive, and had more frequent evidence of splenomegaly
      and hepatic dysfunction. Following univariate and multivariate modeling, only
      AST/ALT ratio, diabetes, splenomegaly and age accurately predicted the stage of
      underlying NAFLD-induced liver disease. CONCLUSION: Hyperferritinemia is common
      in patients with NAFLD but the extent of serum ferritin elevations do not predict
      the stage of underlying NAFLD disease.

PMID- 22457861
TI  - Changes in adipocytokines and insulin sensitivity during and after antiviral
      therapy for hepatitis C genotype 4.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection, especially genotypes 1 and 4, is
      associated with wide metabolic disarrangements. AIM: To assess whether host
      metabolic factors influence sustained virological response (SVR) in patients with
      chronic hepatitis C genotype 4 (HCV-4) treated with peginterferon / ribavirin and
      to evaluate the impact of antiviral therapy on insulin resistance (IR) and serum
      levels of adipocytokines. METHODS: Changes in levels of adiponectin, leptin, TNF
      alpha and the homeostasis model assessment for insulin resistance (HOMA-IR) on
      antiviral combination in patients with HCV-4 were analyzed and effect on response
      was studied. RESULTS: 107 patients were included (M/F 86/21; mean age 41.4+/-5.6
      years). Neither serum adipocytokines nor HOMA-IR was correlated with viral load.
      SVR was achieved by 57% of patients and was associated with fibrosis score (odds
      ratio: 6.5; P = 0.001) and adiponectin level (odds ratio: 1.3; P = 0.01). At the
      end of follow-up, HOMA-IR, adiponectin, leptin and TNF-alpha were reduced, all
      these changes unrelated to predicting the outcome of treatment. At follow-up,
      HOMA-IR and adiponectin continued to decrease in patients with SVR, but remained
      unchanged significantly in patients who did not response or relapse. CONCLUSIONS:
      Serum adiponectin at baseline appears to be an independent predictor for the
      achievement of SVR and can be utilized as an additional predictive marker.
      Changes of IR and adipocytokines occur under treatment which is more evident with
      the resolution of HCV infection, suggesting that HCV could have a direct role in
      these metabolic changes.

PMID- 22457862
TI  - Early treatment in Crohn's disease: do we have enough evidence to reverse the
      therapeutic pyramid?
AB  - Current guidelines on the medical therapy of Crohn's disease recommend a step-up
      strategy consisting of a progressive intensification of treatment as the disease
      severity increases. In the last fifteen years, the introduction of biologic
      therapies, particularly anti-TNFalpha antibodies, has offered new therapeutic
      opportunities. The efficacy of anti-TNF-alpha therapy for inducing and
      maintaining clinical response or remission in moderate to severe Crohn's disease
      has been extensively evaluated in randomised controlled trials and meta-analyses.
      Moreover, anti-TNF-alpha therapy can induce mucosal healing and this property may
      be potentially disease-modifying. Consequently, an early introduction of
      biologics and/or immunomodulators (top-down strategy) in newly diagnosed Crohn's
      disease has been advocated. This paper will review the evidence in favour and
      against this approach to Crohn's disease therapy, discuss which patients are
      potential candidates to early aggressive treatment, and how a conventional step
      up approach can be optimized. The conclusion is that an indiscriminate top-down
      approach does not seem to be appropriate for all patients with moderate to severe
      Crohn's disease.

PMID- 22457863
TI  - Gastrointestinal involvement in spinal cord injury: a clinical perspective.
AB  - Bowel problems occur in 27% to 62% of patients with spinal cord injuries (SCI),
      most commonly constipation, distention, abdominal pain, rectal bleeding,
      hemorrhoids, bowel accidents, and autonomic hyperreflexia. The acute abdomen,
      with a mortality of 9.5%, does not present with rigidity or absent bowel sounds
      but rather with dull/poorly-localized pain, vomiting, or restlessness, with
      tenderness, fever, and leukocytosis in up to 50% of patients. Fecal impaction may
      present with anorexia and nausea. Methods used for bowel care include laxatives,
      anal massage, manual evacuation, and enemas. Randomized, double-blind studies
      demonstrated the effectiveness of neostigmine, which increases cholinergic tone,
      combined with glycopyrrolate, an anticholinergic agent with minimal activity in
      the colon that reduces extracolonic side-effects. Improved bowel function occurs
      with anterior sacral root stimulators which may be combined with an S2 to S4
      posterior sacral rhizotomy which interrupts the reflex arc by cutting the
      posterior roots carrying the spasticity-causing sensory nerves. For severe
      constipation, a colostomy reduces time for bowel care, providing a clean
      environment so decubitus ulcers may heal. Gallstones occur in 17% to 31% of
      patients, and acalculous cholecystitis in 3.7% of patients with acute SCI. A high
      index of suspicion is needed to properly diagnose bowel problems in SCI.

PMID- 22457864
TI  - Colorectal liver metastases: an update on palliative treatment options.
AB  - Only approximately 30% of patients with colorectal cancer liver metastasis
      qualify for curative therapy, which is in most cases liver lesion resection. Due
      primarily to the extent of the tumors and patient comorbidities, palliative
      therapy remains the only option in non-resection cases. Palliation enables local,
      symptomatic control and prolonged survival in some cases. As established methods
      are continuously improved, new palliative therapy methods are tested in clinical
      trials and subsequently introduced into clinical practice. The present review
      provides an overview of current colorectal liver metastasis treatment when
      resection is not an option. This review gives the basis for an interdisciplinary
      decision making process for the treatment of liver metastasis.

PMID- 22457865
TI  - Acquired haemophilia complicated with gastrointestinal bleeding and spontaneous
      iliopsoas muscle haematoma in a woman with chronic C hepatitis under treatment
      with pegylated IFN alpha 2a and ribavirin.
AB  - Acquired haemophilia A is a very rare (1-2 cases per million people) but often
      life-threatening haemorrhagic disorder characterized by antibodies directed
      against coagulation factor VIII. We report the case of a 55-year old woman under
      treatment with Pegylated alpha 2a interferon (IFN) and Ribavirin for chronic
      viral C hepatitis, who developed a progressive severe haemorrhagic syndrome
      diagnosed as acquired haemophilia based on supplementary laboratory data
      (prolonged activated partial thromboplastin time, extremely low factor VIII level
      - 1%, high titre of factor VIII inhibitor - 30 Bethesda U/ml).The onset was
      insidious, about three months before presenting to our unit. Antiviral therapy
      had been stopped three weeks before current admission. Emergency intensive
      treatment included: haemostatic agents - rFVII (Novoseven), FEIBA (Factor VIII
      Inhibitor Bypassing Activity), vitamin K, adrenostazin, cryoprecipitate, fresh
      frozen plasma, as well as immunosuppressive therapy (high dose corticotherapy and
      cyclophoshamide), immunoglobulins (Humaglobin), prophylactic PPI and antibiotics.
      The evolution was slowly favourable with the remission of the haemorrhagic
      syndrome and regression of the iliopsoas muscle haematoma. Clinicians should be
      aware that acquired forms of haemophilia do exist, representing a rare diagnosis
      and a therapeutic challenge. To our knowledge, this is the first reported case of
      acquired haemophilia in Romania, in a patient with chronic viral C hepatitis
      under antiviral treatment.

PMID- 22457866
TI  - Russell body gastritis: case report and review of the literature.
AB  - An unusual and rare gastric mucosal lesion histologically consisting of Russell
      bodies and plasma cell infiltration and termed as Russell body gastritis is
      presented. In the literature there are only ten such case reports and of these,
      seven including this present case were associated with Helicobacter pylori
      infection. The high rate of Helicobacter pylori infections in cases of Russell
      body gastritis suggests that the correlation is not merely coincidental. All data
      in the literature related to Russell body gastritis were scanned, and
      histopathologic findings and the clinical characteristics associated with such
      lesions were discussed.

PMID- 22457867
TI  - Gastrointestinal stromal tumor (GIST) associated with synchronous colon
      adenocarcinoma - a case report.
AB  - Gastrointestinal stromal tumors (GIST) are rare mesenchymal neoplasms of the
      gastrointestinal tract with a malignant potential and unpredictable behavior. In
      the literature a few cases of synchronous development of a GIST and another
      neoplasia with different incidence, etiology, evolution and prognostic have been
      described. We report a case of a 61 year old male with a simultaneous occurrence
      of a GIST and a colon adenocarcinoma.

PMID- 22457868
TI  - Tuberculosis and the pancreas: a diagnostic challenge solved by endoscopic
      ultrasound. A case series.
AB  - Pancreatic tuberculosis is a rare disease. It can be easily confused with
      malignancy or pancreatitis on imaging. This could result in unnecessary surgery.
      As this is a treatable disease it is imperative to diagnose this condition pre
      operatively. We report three cases of pancreatic tuberculosis that were diagnosed
      by endoscopic ultrasound. In conclusion, endoscopic ultrasound is the diagnostic
      modality of choice for pancreatic tuberculosis facilitating high resolution
      imaging, as well as sampling of tissue for staining, cytology, culture and
      polymerase chain reaction assay.

PMID- 22457869
TI  - Clinical feature of a small intestinal mucosal injury in chronic NSAID users in
      Japan.

PMID- 22457870
TI  - Hepatic arteriovenous malformation in Rendu-Osler-Weber syndrome.

PMID- 22457871
TI  - Clostridium difficile infection in gastroenterology settings: more frequent or
      better diagnosed?

PMID- 22457872
TI  - Retraction. Parsian H, Rahimipour A, Nouri M, Somi MH, Qujeq D, Fard MK, Agcheli
      K. Serum hyaluronic acid and laminin as biomarkers in liver fibrosis. J
      Gastrointestin Liver Dis 2010; 19 (2): 169-174.

PMID- 22457873
TI  - Chiral acid selectivity displayed by PEDOT electropolymerised in the presence of
      chiral molecules.
AB  - Chiral conducting polymers prepared by electropolymerising PEDOT in the presence
      of chiral anions such as hyaluronic acid and anionic collagen or in a chiral
      nematic phase (hydroxypropyl cellulose, HPC) show excellent chiral acid
      recognition. This paper demonstrates the enantioselective recognition and
      transfer of protonated mandelic acid and protons using chiral PEDOTs.
      Discrimination between (R)-(-)- and (S)-(+)-mandelic acid was observed using
      cyclic voltammetry and square-wave voltammetry.

PMID- 22457874
TI  - Au@SiO2 core-shell nanoparticles for laser desorption/ionization time of flight
      mass spectrometry.
AB  - In matrix-assisted laser desorption/ionization time of flight mass spectrometry
      (MALDI-TOF-MS), the analysis capability, especially for small molecules, is often
      compromised by the addition of organic matrices due to the existence of
      background signals. Herein we report a new detection method on the utility of
      core-shell nanoparticles (CSNPs) as energy transfer structure in LDI-TOF-MS. The
      LDI-TOF-MS based on gold-silica core-shell nanoparticles with ultrathin silica
      shell of 2-4 nm (Au@utSiO(2) CSNPs) was effectively applied to the analysis of
      many compounds, especially for small functional molecules and polymers, which was
      more promising than MALDI-TOF-MS.

PMID- 22457875
TI  - Magnetic cellulose-chitosan hydrogels prepared from ionic liquids as reusable
      adsorbent for removal of heavy metal ions.
AB  - Magnetic hybrid hydrogels with a novel polymeric coating consisting of chitosan
      and cellulose were prepared. By coating cellulose and chitosan, we combined the
      renewability and biocompatibility of cellulose and chitosan as well as the
      magnetic properties of Fe(3)O(4) to create a hybrid system to adsorb heavy
      metals.

PMID- 22457876
TI  - Monoacylglycerols as transmembrane Cl- anion transporters.
AB  - We report that the amphiphilic natural product, monoacylglycerol 1, functions as
      a transmembrane Cl(-)/NO(3)(-) anion transporter. The 1,2-diol group is crucial
      for the transport function since diacylglycerol and triacylglycerol analogs are
      not anion transporters. Furthermore, adding another hydrogen bond donor to the
      glycerol head-group and perfluorination of the acyl tail gave synthetic analogs
      with improved Cl(-) membrane transport properties.

PMID- 22457877
TI  - Cryo-EM--the first thirty years.
AB  - Thirty years ago, in December 1981, The Journal of Microscopy published a very
      short paper entitled 'Vitrification of pure water for electron microscopy'. It
      turned out to be important for the development of cryo-electron microscopy and it
      contributed to reverse, from foe to friend, the status of water in electron
      microscopists' minds. This change has brought obvious gains. The future will tell
      how many more are still to come.

PMID- 22457878
TI  - [Neuroendocrine tumors of the gastroenteropancreatic system. An interdisciplinary
      challenge].

PMID- 22457879
TI  - [Genetic risk of atopic dermatitis. Epidermal barrier and immunological
      dysregulation].

PMID- 22457881
TI  - Fleet afoot: what's new in the realm of ambulance safety?

PMID- 22457880
TI  - Self portrait: what does the National EMS Assessment tell us about ourselves?

PMID- 22457882
TI  - Hippocratic Oath.

PMID- 22457892
TI  - The disgrace of commodification and shameful convenience: a critical race
      critique of the NBA.
AB  - This essay positions sport as a pedagogical social institution from which people
      learn about race, gender, power, and privilege. The National Basketball
      Association is examined closely with a critical race lens with regard to the
      commodification of Black masculinity. A critical race analysis reveals the sharp
      contradictions between the league's progressive image as an "industry leader" of
      racial diversity (Lapchick, Bustamante, & Ruiz, 2007, p.1) and the actualization
      of league discourse, policy, and practice.

PMID- 22457894
TI  - Black women talk about workplace stress and how they cope.
AB  - Black women face the same struggles as White women; however, they have to face
      issues of diversity on top of inequality. The purpose of this study was to
      explore work-related stressors that affect the lives of Black women and how they
      cope with them. Using an exploratory design with grounded-theory methods, five
      basic themes emerged that identify when racism and sexism are experienced as
      stressors for African American women in the workplace. The themes are: (1) being
      hired or promoted in the workplace, (2) defending one's race and lack of
      mentorship, (3) shifting or code switching to overcome barriers to employment,
      (4) coping with racism and discrimination, and (5) being isolated and/or
      excluded. The results from this study indicate African American women use emotion
      and problem-focused coping responses to manage stress (e.g., racism and sexism)
      in the workplace. The article concludes with a discussion of practice
      implications of these findings.

PMID- 22457895
TI  - The man with the dirty black beard: race, class, and schools in the antebellum
      South.
AB  - The problem of poor, degraded white people in the antebellum South presented a
      problem to both reformers and proponents of slavery. Sharpening the differences
      of race meant easing those of class, ensuring that public schooling did not
      always receive widespread support. The cult of white superiority absolved the
      state of responsibility for social mobility. As better schooling was advocated
      for religious and civic reasons, wealthy planters determined to avoid taxes
      joined with their illiterate neighbors in fighting attempts at "improvement" that
      undermined the slave system based on the notion of black inferiority.

PMID- 22457896
TI  - "So truly afflicting and distressing to me his sorrowing mother": expressions of
      maternal grief in eighteenth-century Philadelphia.
AB  - In 1781, Lowry Wister produced an eight-page account of her three-year son's
      death from small pox. Lowry Wister's narrative offers important insights into the
      emotional landscape of mothering, mourning, and religion in late eighteenth
      century America. Religious and cultural prescriptions stressed restraint
      throughout the mourning process, and in particular admonished women to avoid
      excessive displays of grief. Lowry Wister's emotional struggles as a "sorrowing
      mother" enable us to examine the relationship between individual experiences and
      prescribed expressions of grief and mourning. While eighteenth-century
      conventions stressed quiet resignation to God's will, emerging cultural changes
      increasingly enabled - indeed, encouraged - women to give public voice to their
      private emotions. By the nineteenth century, sentimental views of childhood,
      along with a culture of mourning, inspired parents - especially mothers - to give
      full expression to intense feelings of loss and sorrow. Lowry Wister's narrative
      reveals how women responded to and negotiated various religious, cultural and
      literary conventions that shaped their understandings of motherhood and mourning.
      Her narrative illustrates the various ways in which individual women challenged
      cultural norms and helped usher in new forms of emotional and literary
      expression. Comparisons of Wister's narrative to other eighteenth-century women's
      writings on grief and mourning further illuminate the interplay between cultural
      convention and individual expression.

PMID- 22457898
TI  - Camp Chase Prison: a study of power and resistance on the northern home front,
      1863.

PMID- 22457899
TI  - The National Cash Register Company and the neighborhoods: new perspectives on
      relief in the Dayton flood of 1913.

PMID- 22457900
TI  - Challenges in biocooperative rehabilitation robotics.
AB  - Psychological states such as mood, motivation and engagement are known to be
      critical for the success of rehabilitation, and encouraging unmotivated stroke
      patients improves the likelihood of their eventual recovery. Psychological
      factors can be incorporated into the closed-loop control of biocooperative
      rehabilitation systems, augmenting the device with critical information about the
      patient state. However, in rehabilitation robotics, interpretation of
      psychophysiological measurements is made complex by the multi-task environment,
      the presence of strenuous physical activity and patient's damage to the central
      and autonomic nervous systems. The study examines these challenges and proposes
      possible solutions for implementation in biocooperative control of rehabilitation
      robots.

PMID- 22457901
TI  - Uncontrolled manifold analysis of standing-up motion for development of an
      assistance system.
AB  - Standing-up motion is essential to performance of the activities of daily life
      (ADL). In this research, we analyse human standing-up motion in terms of how
      joint angles coordinate to contribute to the motion. Uncontrolled manifold (UCM)
      analysis is applied, and degrees of joint coordination are calculated for the
      entire course of the motion. Those values are investigated for the four phases of
      the motion to understand which positions of the body are under explicit control.
      Results indicate that individuals control their hip and shoulder positions in the
      horizontal direction until extending their upper body and also after they finish
      lifting up their body. On the other hand, it is shown that vertical direction of
      the hip and shoulder are controlled until the time they bend their back and lift
      up their hip. Based on time series of calculated joint coordination over the
      entire standing-up motion, we suggest a new control method for our previously
      developed force assisting system. The controller allows deviated range of
      movement during the time points in which healthy participants show less explicit
      control of their body positions, and requires more consistent trajectories during
      times when participants show more explicit control.

PMID- 22457903
TI  - Abstracts of the 9th Liver Update, July 13-17, 2011, Petaling Jaya, Malasia.

PMID- 22457902
TI  - Rendering potential wearable robot designs with the LOPES gait trainer.
AB  - In recent years, wearable robots (WRs) for rehabilitation, personal assistance,
      or human augmentation are gaining increasing interest. To make these devices more
      energy efficient, radical changes to the mechanical structure of the device are
      being considered. However, it remains very difficult to predict how people will
      respond to, and interact with, WRs that differ in terms of mechanical design.
      Users may adjust their gait pattern in response to the mechanical restrictions or
      properties of the device. The goal of this pilot study is to show the feasibility
      of rendering the mechanical properties of different potential WR designs using
      the robotic gait training device LOPES. This paper describes a new method that
      selectively cancels the dynamics of LOPES itself and adds the dynamics of the
      rendered WR using two parallel inverse models. Adaptive frequency oscillators
      were used to get estimates of the joint position, velocity, and acceleration.
      Using the inverse models, different WR designs can be evaluated, eliminating the
      need to build several prototypes. As a proof of principle, we simulated the
      effect of a very simple WR that consisted of a mass attached to the ankles.
      Preliminary results show that we are partially able to cancel the dynamics of
      LOPES. Additionally, the simulation of the mass showed an increase in muscle
      activity but not in the same level as during the control, where subjects actually
      carried the mass. In conclusion, the results in this paper suggest that LOPES can
      be used to render different WRs. In addition, it is very likely that the results
      can be further optimized when more effort is put in retrieving proper estimations
      for the velocity and acceleration, which are required for the inverse models.

PMID- 22457904
TI  - [Best practices in perinatology. Best practices of the Neonatal Czech Society].

PMID- 22457905
TI  - Abstracts of the 11th Congress of the World Federation of Interventional and
      Therapeutic Neuroradiology, November 8-11, 2011, Cape Town, South Africa.

PMID- 22457906
TI  - [Abstracts of the 52nd National Congress of the Italian Society of Nephrology,
      September 21-24, 2011, Geneva, Switzerland].

PMID- 22457907
TI  - [Proceedings of the conference "New Challenges for Occupational Medicine:
      Immigration - Health Promotion." November 6, 2010, Brescia, Italy].

PMID- 22457908
TI  - Psychophysiological responses to robot training in different recovery phases
      after stroke.
AB  - Psychophysiological responses have become a valuable tool in human-robot
      interaction since they provide an objective estimate of the user's psychological
      state. Unfortunately, their usefulness in rehabilitation robotics is uncertain
      since they are influenced by both physical activity and pathological conditions
      such as stroke. We performed psychophysiological measurements in subacute and
      chronic stroke patients as well as healthy controls during a reaching and
      grasping exercise task performed in a multimodal virtual environment.
      Furthermore, we evaluated the differences in kinematic and static parameters
      between the three groups of subjects. The results of the observed kinematic and
      static evaluation parameters showed significant differences when different
      assistive modes enabled the subject to focus on a particular function of the
      exercise, like reaching or grasping, or coordinated actions that combine reaching
      and grasping, reflecting the motor abilities of the individual. The analysis of
      psychophysiological responses suggests that both chronic and subacute stroke
      subjects have weaker psychophysiological responses than healthy subjects, though
      the responses of chronic patients have recovered somewhat. This certainly
      indicates that further studies are needed before psychophysiological responses
      can be used in clinical practice.

PMID- 22457909
TI  - Quality, safety, outcomes: do we need a unified approach?

PMID- 22457910
TI  - [Commentary on the guidelines for clinical evaluation of diagnostic
      radiopharmaceuticals by the Japanese Society of Nuclear Medicine (2). The
      guidance on development of radiopharmaceuticals for diagnostic imagings in the
      United States and Europe].

PMID- 22457911
TI  - [The past, present and future of anesthesiology: Scientific and clinical
      development for the near future].

PMID- 22457912
TI  - [HIV infection. Status of the epidemic and the latest therapy].

PMID- 22457913
TI  - [Discovery of the pulmonary circulation by Inv Nafis in 13th century].

PMID- 22457914
TI  - [Research on the Ikeda Documents(40)].

PMID- 22457915
TI  - H-2 antigen variants in a cultured heterozygous mouse leukemia cell line. VI.
      Rate of emergence of the hemizygous variants and evidence that the variants
      preexist the selection.
AB  - The rates of emergence of H-2b- and H-2d- variants from an H-2b+/ H-2d+
      heterozygous mouse leukemia cell line were determined by fluctuation analyses.
      The results show that the wild type cells throw off the H-2b- variants at about
      10(-5) per cell per generation and the H-2d- variants at 10(-6) per cell per
      generation. The reason for this tenfold difference in the rates for the two
      symmetrical variants is not clear. The fluctuation analyses also indicate that
      the variants exist in the wild type population prior to exposure to the selective
      agents.

PMID- 22457916
TI  - H-2 antigen variants in a cultured heterozygous mouse leukemia cell line. VII.
      Effect of selection with a hybridoma antibody.
AB  - An (H-2k/H-2d)F1 sarcoma cell line was subjected to immunoselection using ascites
      fluid from a mouse growing a hybridoma secreting an anti H-2Kk antibody.One
      hundred random clones were picked from the surviving population and screened by
      direct cytolysis using the hybridoma antibody or alloantisera against H-2Kk and H
      2Dk. Fifty-nine clones were resistant to all three antisera, indicating that they
      no longer expressed the entire H-2k haplotype. Thirty-two were resistant to the
      ascites and to the anti H-2Kk alloantiserum, but sensitive to the anti H-2Dk
      serum, indicating that they had lost H-2Kk antigen, but retained H-2Dk. Nine
      clones were sensitive to the alloantisera, but resistant to the hybridoma,
      indicating that, though they retained the product(s) recognized by the
      alloantiserum against H-2Kk, they had lost the site(s) that bound the hybridoma
      antibody. Quantitative absorption assays using lymph-node cells from young BALB.K
      (H-2Kk) mice as targets show that one representative clone from the last group
      absorbs the anti H-2Kk activity in the alloantiserum. This implies that the
      sensitivity of the variant clone to the alloantiserum is not due to contaminating
      anti C-type virus antibodies in the serum. The possible implications of these
      data are discussed.

PMID- 22457917
TI  - A public HLA antigen associated with HLA-A9, Aw32, and Bw4.
AB  - The HLA complex codes for three distinct 44000 dalton molecules associated with
      beta2 microglobulin--HLA-A, B and C--each with its own multiallelic series of
      private antigens. The HLA-B molecule is exceptional in that it also carries a
      diallelic system, Bw4 and Bw6. One of these, Bw4, is often associated with the A
      locus specificity A9. This finding has usually been ascribed to linkage
      disequilibrium between A- and B-locus antigens. We have shown, however, that an
      epitope called LHe is actually shared by A-locus and B-locus molecules. This
      epitope is found on all HLA-B molecules bearing the Bw4 determinant and is also
      found on all HLA-A molecules carrying the A9 (Aw23 and Aw24) or Aw32
      specificities. We consider this a "public" HLA antigen; the possible molecular
      basis for both subtypic and public antigens on a single glycoprotein is
      discussed.

PMID- 22457918
TI  - Identification of two Ia-like alloantigens on rabbit B lymphocytes.
AB  - Alloimmunizations with rabbit lymphoid cells have resulted in the identification
      of two cell-surface alloantigens, Ia1 and Ia2. These antigens reside on nearly
      all B cells; few, if any thymus cells or T cells of mesenteric lymph nodes bear
      these antigens. Genetic studies showed that Ia1 and Ia2 molecules appear to be
      controlled by allelic genes at a locus closely linked to the MHC. Immunochemical
      analyses revealed that Ia1 and Ia2 are glycoproteins and that each is composed of
      two polypeptide chains of molecular weights of 28 000 and 30 000-32 000. Thus,
      the alloantigens identified by these two antisera appear to be Ia-like molecules.

PMID- 22457919
TI  - Genetic polymorphism of serum complement components in the chimpanzee.
AB  - Significant polymorphism of serum complement components Bf, C2, C3, C6, and C8 in
      the chimpanzee has been demonstrated. The data are consistent with the hypothesis
      that C2 and Bf are closely linked to ChLA and argue against close linkage of ChLA
      to C3 or to C8, as in man. In addition, a blank allele for C6 and C6 deficiency
      was detected in several chimps.

PMID- 22457920
TI  - The spatial relationship of the viral and H-2 antigens recognized by anti-viral
      CTLs.
AB  - With the use of monospecific rabbit anti-G protein and mouse monoclonal anti-H
      2Kk, we have analyzed the spatial relationship of the serologically defined H-2Kk
      antigens and the major surface glycoprotein (G protein) of vesicular stomatitis
      virus (VSV) to those antigens recognized by B10.A (k, d) anti-VSV cytotoxic T
      lymphocytes (CTLs). The ability of monoclonal anti-H-2Kk or rabbit anti-G protein
      to inhibit specifically the cytolytic activity of B10.A anti-VSV CTLs indicates
      that the G protein and the H-2Kk molecules are in close proximity to the viral
      and H-2Kk antigens recognized by the anti-VSV (CTLs. By the method of sequential
      immunoprecipitation, we also demonstrated that only 10-30 percent of the
      serologically defined G and H-2Kk molecules are in the G-H-2Kk complexes.

PMID- 22457921
TI  - T lymphocytes responding to Mls-locus antigens are Lyt-1+, 2- and I-A restricted.
AB  - We have investigated primary and secondary responses of mouse splenic T cells to
      strong mixed lymphocyte stimulating antigens controlled by the Mls locus using
      MHC-identical mixtures of cells. Our studies show that strong primary Mls-locus
      specific responses involve recognition of self I-A antigens, since BUdR and light
      suicide or F1 into parent radiation bone-marrow chimeras both demonstrate a
      preference of unprimed F1 T cells to respond to Mls-locus antigens associated
      with one parent's MHC antigens. Furthermore, conventional anti-I-A antisera and
      monoclonal anti-I-A antibody both inhibit Mls-locus responses in an MHC-specific
      manner. Finally, as is typical of T cells responding to I-A antigens or to
      nominal antigens associated with self I-A, Mls-locus responses are mediated by
      Lyt-1+, 2 cells. One striking finding in these studies was the very high
      frequency of cells capable of responding to Mls-locus antigens, the highest being
      1/300 splenic T cells. This plus evidence for recruitment during primary Mls
      locus responses may account for reports of a lack of I-A restriction in secondary
      anti-Mls locus responses to strong Mls-locus antigens, a finding with which we
      concur. The possibility that these secondary responses between noncongenic
      strains of mice may be directed at other genetic loci is also discussed. These
      experiments leave open the question of the biological role of the Mls-locus and
      of the very large number of T cells reactive to it.

PMID- 22457922
TI  - Genetic control of the serum concentration of an H-2-antigen-like polypeptide
      chain.
AB  - Mouse serum contains a protein complex consisting of at least three polypeptide
      chains. One of the chains with an approximate molecular weight of 40000 is
      similar to the heavy chain of normal H-2 antigens. The serum concentration of
      this 40000 dalton chain is under genetic control. Formal genetic analyses in
      B10.M and B10.S mice, their F1 progeny and in backcrosses show that there are two
      codominantly expressed alleles at a single locus regulating the serum
      concentration. Measurements of the 40 000 dalton chain in recombinant mice
      suggest that the controlling locus is situated to the right of the S region.

PMID- 22457923
TI  - Biochemical characterization of murine Ia antigens with xenoantisera. I.
      Identification of a second la molecule (I-E?) in H-2s haplotype.
AB  - Rabbit anti-Ia sera was produced by immunization with detergent-solubilized
      extracts from splenic, lymph-node and thymus cells. The antisera contained
      activity against H-2 as well as Ia molecules. By a sequential immunoprecipitation
      assay it was shown that the rabbit anti-mouse H-2s serum precipitated a second Ia
      molecule in the H-2s haplotype. Previous studies with alloantisera have shown
      only one Ia molecule associated with this haplotype. Sequential precipitations
      with alloantiserum against the whole I region were used to show that this second
      Ia molecule is coded by genes within the I region. Since only I-A- and I-E-region
      coded molecules are immunoprecipitable in most haplotypes, we presume that the
      rabbit antiserum could be identifying the I-E-subregion coded molecule in the H
      2s haplotype. The rabbit antiserum reacts with an isotypic specificity on the
      molecule. The studies suggest that the I-E subregion does exist in the H-2s
      haplotype even though alloantiserum cannot be produced to identify allotypic
      variants associated with this subregion.

PMID- 22457924
TI  - Anti-H-2 antibodies induced by syngeneic immunization.
AB  - Abstract. Alloreactive cytotoxic antibodies were induced in BALB/c mice by
      syngeneic immunization with normal lymphoid cells. Sixteen out of 41 mice
      produced antibodies with distinct anti-H-2 specificity. Anti-Kk antibodies were
      present in all positive sera, but the individual sera produced different
      reactivity patterns when tested on a panel of H-2 haplotypes. Absorption and
      immunoprecipitation experiments confirmed the H-2 specificity of the syngeneic
      sera. We hypothesize that virus-modified H-2d structures have triggered
      alloreactive B-cell clones to produce anti-H-2 antibodies.

PMID- 22457925
TI  - A new cytotoxic lymphocyte-defined antigen coded by a gene closely linked to the
      H-3 locus.
AB  - F1 complementation results indicate that a new gene, putatively controlling a
      minor histocompatibility antigen, is closely linked to the minor
      histocompatibility gene, H-3, in the fifth linkage group of chromosome 2 of the
      mouse. This gene controls a product that was capable of inducing as well as
      acting as a target for cytotoxic lymphocytes (CTL). The lytic activity of CTL
      developed in B10.LP-H-3D mice specific for the product of the new gene of B10 was
      restricted to target cells possessing H-2Db antigens. This contrasts to the H-2Kb
      restricted activity of H-3.1 specific CTL.

PMID- 22457926
TI  - The partial isolation of subcellular MHC products which are recognized by
      alloimmune T lymphocytes.
AB  - H-2 antigens from three murine tumor-cell lines (YAC, EL-4 and P815) were
      solubilized with triton X-100 and separated by SDS-polyacrylamide gel
      electrophoresis. Proteins were eluted from gel slices and assayed for inhibition
      by a target-effector binding (TBC) assay. Fractions inhibiting alloimmune T cells
      also contained serologically detectable H-2 molecules as judged by a complement
      dependent microcytotoxicity-inhibition assay. Fractions containing Moloney cell
      surface antigen (MCSA), gp 71, or p30 did not inhibit alloimmune TBC. H-2
      antigens were selective for T cells since they failed to inhibit binding of
      natural killer (NK) cells to NK-sensitive targets, whereas, in the reciprocal
      experiment, the NK target antigens inhibited NK cells but not alloimmune T cell
      binding to intact targets. Cross inhibition tests in the T-cell system revealed
      that the H-2 molecules maintained their specific antigenic structure. These
      observations suggest that it will be possible to characterize further those parts
      of the subcellular H-2 preparations reacting with distinct killer T-cell clones.

PMID- 22457927
TI  - Genetic control of acquired resistance to visceral leishmaniasis in mice.
AB  - A series of H-2 and non-H-2 congenic resistant (CR) strains on a C57BL/10Sn
      background were infected with 10(7) amastigotes of Leishmania donovani. Non-H-2
      congenic strains B10.LP-H-3b and B10.CE(30NX) and (B10.LP-H-3b x B10)F1 hybrids
      showed a very rapid decrease in liver-parasite burdens beyond day 21. Parasite
      counts for these strains at day 35 were significantly lower than for all other
      strains tested. The rapid decrease in parasite numbers, massive lymphocellular
      infiltration into the liver and strong delayed hypersensitivity reactions to
      parasite antigens in strains congenic for a portion of chromosome 2 indicated
      that acquired immunity to L. donovani was controlled by a dominant gene at or
      near the Ir-2 locus. In addition, B10.129(10M) mice, which differ from C57BL/10Sn
      at the H-11 locus, showed highly significant increases in parasite numbers at day
      35. Other observations supporting the absence of acquired immunity in
      B10.129(10M) included negative delayed hypersensitivity tests to parasite
      antigens and the absence of lymphocellular infiltrate into the liver. Although
      the differences were not as pronounced, H-2 CR strains with H-2b, H-2a, and H-2k
      haplotypes also showed significantly greater decreases in parasite numbers by day
      35 as compared to other H-2 CR strains.

PMID- 22457928
TI  - A new lymphocyte alloantigen (Ly-10) controlled by a gene linked to the Lyt-1
      locus.
AB  - Spleen cells from a (BALB/c x C57BL/6)F1 mouse immunized with CBA/J spleen cells
      were fused with the myeloma cell line NS-1. One of the six established hybrid
      cell lines continuously secreted antibody that recognized a new antigenic
      specificity, tentatively called "Ly-10.1". This newly found antigen is expressed
      on thymocytes, on splenic T and B cells, on bone-marrow cells, and on the cells
      derived from brain, kidney and liver. It is also expressed on a continuous cell
      line, 416B, with stem-cell characteristics. The unique tissue distribution and,
      furthermore, a distinct strain distribution pattern distinguishes Ly-10.1 from
      any known murine lymphocyte alloantigen. On the basis of reactivity with cells of
      the C57BL/6-Lyt-1a congenic strain, one gene governing Ly-10 expression is
      assigned to the Lyt-1 region of chromosome 19.

PMID- 22457929
TI  - Activation or suppression of bactericidal activity of macrophages during a graft
      versus-host reaction against I-A and I-J-region differences, respectively.
AB  - Systemic graft-versus-host reactions (GVHR) were induced in F1 heterozygous mice
      by injecting 10(8) parental lymphocytes. The Anti-Thy 1.2-sensitive, T-cell
      mediated activation of macrophages was assessed by their increased capacity to
      destroy a facultative intracellular bacterium Listeria monocytogenes. The
      difference in MHC regions causing a GVHR that induced high levels of macrophage
      activation mapped to I-A. In contrast, differences at K or D, in any of the other
      H-2 subregions or in the non-H-2 background, including Mls alone or in
      combination, did not induce a GVHR leading to macrophage activation, unless these
      differences were combined with a difference at I-A. The numbers of parental cells
      needed to activate macrophages via a GVHR caused by I-A vs. non-I-A differences,
      varied at least 30- to 100-fold. When parental cells were injected into F1
      offspring of parents differing at I-J, growth of Listeria was enhanced
      significantly; this negative effect on macrophages was not seen when parental
      combinations differing at I-A alone were compared with those differing at I-A
      plus I-J or I-J plus other H-2 regions.

PMID- 22457930
TI  - Semisyngeneic hybrid resistance to murine teratocarcinoma cells.
AB  - Resistance to two cultured lines of murine embryonal carcinoma was studied in F1
      hybrids constructed between the tumor-syngeneic mouse strain 129/J and several
      allogeneic strains. Three of four such hybrid strains were significantly more
      resistant to the multipotent embryonal carcinoma line PCC3 than the tumor
      syngeneic 129/J parent strain. All hybrid strains tested showed significantly
      higher resistance to the nullipotent embryonal carcinoma line F9 than the
      syngeneic strain. Hybrid resistance to embryonal carcinoma lines does not require
      a hybrid H-2 complex. Several kinds of evidence indicate that this hybrid
      resistance has an immunological basis.

PMID- 22457931
TI  - Anti H-2Dd alloreactivity mediated by herpes-simplex-virus specific cytotoxic H
      2k T lymphocytes is associated with H-2Dk.
AB  - Herpes-simplex-virus (HSV) specific, H-2k-restricted, immune cytotoxic T
      lymphocytes also lyse noninfected H-2d target cells. Genetic mapping studies
      revealed that HSV-specific Dk-restricted CTL cross-react with allogeneic targets
      expressing Dd alloantigens. Cold target inhibition experiments indicate that only
      a minority of HSV-specific CTL mediate cross-reactive cytolysis. The data give an
      example of where the phenomenon of H-2-restricted versus nonrestricted
      responsiveness is not due to distinct subsets of T cells but solely depends on
      the antigenic determinants recognized.

PMID- 22457932
TI  - Heterogeneity of HLA defined in PLT: a cellular assay detects differences not
      seen using HLA-DRw serology.
AB  - The primed lymphocyte typing test (PLT) is used to detect the gene products of
      the HLA-D region which are responsible for secondary restimulation of cells
      primed in MLC. Alternatively, products of the HLA-D region may be detected
      serologically using antisera directed against a subpopulation of lymphocytes;
      these are the so-called DRw determinants. The PLT was used to see if it were
      possible to detect heterogeneity within a given serologically defined group using
      a cellular test. As priming combinations, we used family members identical for
      one haplotype and differing in the HLA-A, B and C regions, but not the D region
      of the second haplotype. Our results indicated that it was possible to prime
      against this second haplotype and that the segregation of the difference followed
      HLA. Therefore, using a cellular test it was possible to detect differences among
      cells belonging to a given DRw group. This suggests that PLT can be a useful tool
      to identify those serological groups which are composed of heterogenous
      determinants. In addition, it points out the problem in using any one test to
      establish identity of the HLA-D region, especially for clinical purposes.

PMID- 22457933
TI  - Surface markers on the T cells that regulate cytotoxic T-cell responses I. The Ly
      phenotype of suppressor T cells changes as a function of time, and is distinct
      from that of helper or cytotoxic T cells.
AB  - Regulatory T cells can be obtained from primary mixed lymphocyte cultures of CBA
      spleen cells responding to BALB/c stimulators. At day 3 of culture, T cells are
      generated which can either help or suppress the generation of cytotoxic T cells
      in a second primary MLC culture. The regulatory activity observed depends on the
      conditions employed in the assay system allowing independent assay of different
      functional cell types which coexist in the cultures. Both the helper activity and
      the suppressor activity are mediated by differentiated antigen-specific T cells
      whose function is radioresistant. The Ly phenotype of these regulatory cells was
      tested. At day 3 of the first-step culture, the phenotype of the helper cells is
      Ly 1.1+ Ly 2.1-, whereas the inhibitory cells are Ly 1.1 Ly 2.1+. At day 5 of M
      LC culture, suppressor activity and helper activity are also observed. However,
      at this point, a suppressor cell which is Ly 1.1-Ly 2.1+ represents the major
      inhibitory activity. It is not clear whether this change in suppressor cell
      phenotype as a function of time in culture represents one differentiation pathway
      or cells derived from two different precursor cells. The Ly phenotype of helper
      or cytotoxic T cells did not change as a function of time in culture. In day 5
      first-step cells, the cytotoxic cells were typed as Ly 1.1+ 2.1+, whereas the
      inhibitory cells present in aliquots of the same treated cell population
      expressed the Ly 1.1- Ly 2.1 phenotype. Taken together, these observations show
      that the antigen-specific suppressor cells and helper cells which regulate the
      generation of cytotoxicity, and the cytotoxic cells themselves represent
      physically distinct subclasses of T cells.

PMID- 22457934
TI  - I-region linked complementing loci in resistance to viral leukemogenesis in the
      mouse.
AB  - A-RadLV, a variant of the radiation leukemia virus, inoculated intrathymically
      into adult mice, causes a high frequency of leukemia in haplotypes b, f, k, d, p
      and j on the B10 background, whereas H-2s mice are resistant. Resistance is
      dominant and segregates with H-2s in the offspring of (b x s)b and (b x t2)b
      backcrosses. Analysis of recombinant strains revealed that resistance is
      associated with I-A and I-B. B10.A(5R), a recombinant of two sensitive
      haplotypes, was found to be resistant, suggesting intra-H-2-gene complementation.
      The resistance of such complementing loci was demonstrated also in the trans
      position by testing F1 mice bred from sensitive parents. These data are taken to
      suggest that I-region linked complementing loci, similar to classical Ir genes,
      may be involved in resistance to murine leukemia.

PMID- 22457935
TI  - Construction and properties of new Lyt-congenic strains and anti-Lyt-2.2 and anti
      Lyt-3.1 monoclonal antibodies.
AB  - Hybridomas producing mouse monoclonal IgM antibodies specific for Lyt-2.2 and Lyt
      3.1 T-cell surface alloantigens have been constructed. Cytotoxic titers of
      ascites fluids were found to be 10(-6) or greater and no lysis of thymocytes of
      congenic strains bearing the alternative allele was observed at the lowest
      dilutions tested (1:2). The anti-Lyt-2.2 monoclonal antibody (HO-2.2)
      specifically precipiated from extracts of Lyt-2.2-positive thymocytes molecular
      species indistinguishable from those precipitated by conventional anti-Lyt-2.2
      sera. However, by immunoprecipitation criteria (though not by cytotoxicity), the
      anti-Lyt-3.1 antibody (HO-3.1) demonstrated some cross-reactivity with similar
      molecular species from Lyt-3.1-negative thymocytes. In addition, three new
      strains of mice differing from existing strains in the region of the Lyt-2 and
      Lyt-3 loci have been constructed. They are: C.C58-Lyt-2a, Lyt-3a and C.AKR-Lyt
      2a, Lyt-3a, congenic with Balb/cAn and bearing Lyt-2a and Lyt-3a alleles of C58/J
      and AKR/J, respectively; and AKR.C-Lyt-2b, Lyt-3b congenic with AKR/J and bearing
      the Lyt-2b and Lyt-3b alleles of Balb/cJ.

PMID- 22457936
TI  - Genetics of the anti-dextran B512 and the autoanti-idiotypic response: codominant
      expression in F1 hybrids and dichotomy of response and allotype-linked idiotype.
AB  - The IgM plaque-forming response to the alpha 1-6 epitope of dextran B512 is
      linked to the Ig-1 heavy chain allotypes j and b characteristic of CBA and C57BL
      strains, respectively, and the response typically induces the formation of
      autoanti-idiotypic antibodies that can distinguish between anti-dextran
      antibodies of CBA and C57BL origin. Nevertheless, some substrains of Balb/c mice
      (allotype a) and some Bailey recombinant stains give a PFC response although they
      do not possess allotypes j or b. The anti-dextran antibodies in these strains
      lack the idiotypes characteristic of either CBA and C57BL antibodies to dextran,
      but they possess their own particular idiotype. F1 hybrids between two responder
      strains possessing different idiotypes on their antibodies against dextran,
      produce both idiotypes and two different autoanti-idiotypic antibodies. CBA(Ig
      1b) mice were high responders to dextran and possessed the idiotype of C57BL,
      whereas C57BL/6(Ig-1a) mice were low responders. The V(H) recombinant strains
      BAB.14 and CB-8KN that possess the Ig-1b allotype of C57BL, but have some of the
      V(H) genes from Balb/c and the rest from C57BL/6 were high responders to dextran,
      but did not possess the C57BL idiotype, suggesting that the genes determining the
      response against dextran and the idiotype may have different locations in the
      heavy chain locus.

PMID- 22457937
TI  - Biochemical identification of rat ART-1 and Ly-1 alloantigens.
AB  - The results of this study indicate that the ART-1 and Ly-1 rat alloantigens are
      synonymous with each other and also with the leukocyte-common (L-C) antigen which
      has been previously identified as a major glycoprotein of rat thymocytes and T
      and B lymphocytes. This conclusion is supported by the following observations:
      (i) when labeling of rat lymphoid cells was studied with a fluorescence-activated
      cell sorter, the profiles obtained were similar for labeling with ART-1 and Ly-1
      alloantibodies and a monoclonal antibody to L-C antigen: (ii) this labeling was
      almost completely inhibited by purified L-C antigen: (iii) preincubation with L-C
      antigen completely inhibited binding of the alloantibodies in a cellular
      radioimmunoassay; (iv) the cytotoxic effect of the alloantibodies was completely
      abolished by preincubation with purified L-C antigen; (v) the strain distribution
      of the ART-1 and Ly-1 alloantigens was identical for 11 rat strains and in
      linkage analysis the ART-1 and Ly-1 alloantigens were found to cosegregate.
      Genetic linkage studies have shown that the L-C antigen locus is unlinked to the
      major histocompatibility antigen (RT1), the immunoglobulin light chain (1k) and
      to the coat color gene (C) loci.

PMID- 22457938
TI  - Serological analysis of xenogeneic anti-lymphoblastoid cell-line sera with
      specificity against HLA-B12.
AB  - In view of the importance of potent anti-HLA sera with narrow reaction patterns
      against defined HLA antigens, two xenogeneic antisera were raised in rabbits
      following immunization with human lymphoblastoid cell lines from HLA-nonidentical
      donors homozygous for HLA-B12. After absorption with lymphoblastoid cell lines of
      an appropriate HLA phenotype, the antisera were purified over DEAE-cellulose ion
      exchange chromatography and reconcentrated. Both antisera recognized HLA-B12
      positive peripheral blood cells of unrelated donors tested in the
      microcytotoxicity assay. The two rabbit antisera revealed a high degree of
      similarity in their anti-HLA-B12 antibody specificity. One antiserum showed some
      cross reactivity with HLA-B13 as has been reported in allo-anti-HLA-B12 sera. The
      other antiserum revealed some activity against HLA-DRw7-positive donors. Antibody
      activity could be removed completely from two further rabbit anti-HLA antisera by
      absorption with lymphoblastoid cell lines from related and unrelated HLA
      identical donors. The advantages of using lymphoblastoid cell lines as immunogens
      and absorption material for the production of heterologous anti-HLA typing sera
      are discussed.

PMID- 22457939
TI  - The Lyb-2 phenotype of hemolytic PFC.

PMID- 22457940
TI  - Susceptibility of allogeneic mice to teratocarcinoma 402AX.

PMID- 22457941
TI  - Spectroscopy and astronomy: H3+ from the laboratory to the Galactic center.
AB  - Since the serendipitous discovery of the Fraunhofer spectrum in the Sun in 1814
      which initiated spectroscopy and astrophysics, spectroscopy developed hand in
      hand with astronomy. I discuss my own work on the infrared spectrum of H3+ from
      its discovery in the laboratory in 1980, in interstellar space in 1996, to recent
      studies in the Galactic center as an example of astronomical spectroscopy. Its
      spin-off, the spectroscopy of simple molecular ions, is also briefly discussed.

PMID- 22457942
TI  - Optical frequency comb spectroscopy.
AB  - Optical frequency combs offer enormous potential in the detection and control of
      atoms and molecules by combining their vast spectral coverage with the extremely
      high spectral resolution of each individual comb component. Sensitive and
      multiplexed trace gas detection via cavity-enhanced direct frequency comb
      spectroscopy has been demonstrated for various molecules and applications;
      however, previous demonstrations have been confined to the visible and near
      infrared wavelength range. Future spectroscopic capabilities are created by
      developing comb sources and spectrometers for the deep ultraviolet and mid
      infrared spectral regions. Here we present a broadband high resolution mid
      infrared frequency comb-based Fourier transform spectrometer operating in the
      important molecular fingerprint spectral region of 2100-3600 cm(-1) (2.8-4.8
      microm). The spectrometer, employing a multipass cell, allows simultaneous
      acquisition of broadband, high resolution spectra (down to 0.0035 cm(-1) of many
      molecular species at concentrations in the part-per-billion range in less than 1
      min acquisition time. The system enables precise measurements of concentration
      even in gas mixtures that exhibit continuous absorption bands. The current
      sensitivity, 2 x 10(-8) cm(-1) Hz-1/2 per spectral element, is expected to
      improve by two orders of magnitude with an external enhancement cavity. We have
      demonstrated this sensitivity increase by combining cavity-enhanced frequency
      comb spectroscopy with a scanning Fourier transform spectrometer in the near
      infrared region and achieving a sensitivity of 4.7 x 10(-10) cm(-1) Hz(-1/2). A
      cavity-enhanced mid-infrared comb spectrometer will provide a near real-time,
      high sensitivity, high resolution, precisely frequency calibrated, broad
      bandwidth system for many applications.

PMID- 22457943
TI  - Tailored molecular samples for precision spectroscopy experiments.
AB  - The resolution of any spectroscopy experiment is ultimately limited by the
      observation time. The ability to produce slow, yet intense molecular beams
      significantly increases the attainable observation time and thus the resolution
      in the spectroscopic experiment. Such slow molecular samples are ideal starting
      points for novel precision spectroscopy experiments aiming at, for example,
      determining the time variation of fundamental constants or the effect of parity
      violation in chiral molecules. We consider the use of decelerated chiral polar
      molecules to perform very high-resolution rotational spectroscopy aiming at
      measuring the energy difference of the two enantiomers due to parity violation.
      Using molecule velocities around 20 m s(-1) and a microwave resonator consisting
      of 50 cm-reflectors (in diameter) and a reflector distance of up to one meter,
      spectral resolutions on the order of only a few Hz become feasible using Fourier
      transform microwave spectroscopy. This should be sufficient to resolve the parity
      violation effect for species containing heavy atoms, such as SOCH3Ph and SeOFI.
      We also discuss the possibilities to use trapped molecules for high-resolution
      spectroscopy--and work out their advantages, such as long observation times, and
      their disadvantages, such as line broadening due to the inhomogeneous trapping
      fields.

PMID- 22457944
TI  - Towards measuring the ionisation and dissociation energies of molecular hydrogen
      with sub-MHz accuracy.
AB  - The most precise determination of the ionisation and dissociation energies of
      molecular hydrogen H2 was carried out recently by measuring three intervals
      independently: the X --> EF interval, the EF --> n = 54p interval, and the
      electron binding energy of the n = 54p Rydberg state. The values of the
      ionisation and dissociation energies obtained for H2, and for HD and D2 in
      similar measurements, are in agreement with the results of the latest ab initio
      calculations [Piszczatowski et al., J. Chem. Theory Comput., 2009, 5, 3039;
      Pachucki and Komasa, Phys. Chem. Chem. Phys., 2010, 12, 9188] within the combined
      uncertainty limit of 30 MHz (0.001 cm(-1)). We report on a new determination of
      the electron binding energies of H2 Rydberg states with principal quantum numbers
      in the range n = 51-64 with a precision of better than 100 kHz using a
      combination of millimetre-wave spectroscopy and multichannel quantum-defect
      theory (MQDT). The positions of 33 np (S = 0) Rydberg states of ortho-H2 relative
      to the position of the reference 51d (N+ = 1, N = 1, G+ = 1/2, G = 1, F = 0)
      Rydberg state have been determined with a precision and accuracy of 50 kHz. By
      analysing these positions using MQDT, the electron binding energy of the
      reference state could be determined to be 42.3009108(14) cm(-1), which represents
      an improvement by a factor of -7 over the previous value obtained by Osterwalder
      et al [J. Chem. Phys., 2004, 121, 11810]. Because the electron binding energy of
      the high-n Rydberg states will ultimately be the limiting factor in our method of
      determining the ionisation and dissociation energies of molecular hydrogen, this
      result opens up the possibility of carrying out a new determination of these
      quantities. By evaluating several schemes for the new measurement, the precision
      limit is estimated to be 50-100 kHz, approaching the fundamental limit for
      theoretical values of -10 kHz imposed by the current uncertainty of the proton-to
      electron mass ratio.

PMID- 22457945
TI  - Synchrotron-based highest resolution Fourier Transform infrared spectroscopy of
      naphthalene (C10H8) and indole (C8H7N) and its application to astrophysical
      problems.
AB  - We report a rotationally resolved analysis of the high resolution FTIR spectrum
      of naphthalene which can be considered as a prototypical molecule for polycyclic
      aromatic hydrocarbons (PAHs), and a similar analysis for the prototypical
      heterocyclic aromatic molecule indole. The spectra have been measured using a
      resolution of 0.0008 cm(-1) (21 MHz) with the new high resolution FTIR prototype
      spectrometer of the Molecular Kinetics and Spectroscopy Group at ETH Zurich. The
      spectrometer is connected to the infrared port available at the Swiss Light
      Source (SLS) at the Paul-Scherrer-Institute (PSI). Due to the high brightness of
      the synchrotron radiation in the spectral region of interest, effectively up to
      20 times brighter than thermal sources, and the high resolution of the new
      interferometer, it was possible to record the rotationally resolved infrared
      spectra of naphthalene and indole at room temperature, and to analyse the nu46 c
      type band (nu(0) = 782.330949 cm(-1)) of naphthalene as well as the nu35 c-type
      band (nu(0) = 738.483592 cm(-1)) of indole and an a-type band at nu(0) =
      790.864370 cm(-1) tentatively assigned as the overtone 2nu(40) of indole. The
      results of the naphthalene band analysis are discussed in relation to the
      Unidentified Infrared Band (UIB) found in interstellar spectra at 12.8 MUm.

PMID- 22457946
TI  - Spectroscopy of molecules in very high rotational states using an optical
      centrifuge.
AB  - We have developed a high power optical centrifuge for measuring the spectroscopy
      of molecules in extreme rotational states. The optical centrifuge has a pulse
      energy that is more than 2 orders of magnitude greater than in earlier
      instruments. The large pulse energy allows us to drive substantial number
      densities of molecules to extreme rotational states in order to measure new
      spectroscopic transitions that are not accessible with traditional methods. Here
      we demonstrate the use of the optical centrifuge for measuring IR transitions of
      N2O from states that have been inaccessible until now. In these studies, the
      optical centrifuge drives N2O molecules into states with J ~ 200 and we use high
      resolution transient IR probing to measure the appearance of population in states
      with J = 93-99 that result from collisional cooling of the centrifuged molecules.
      High resolution Doppler broadened line profile measurements yield information
      about the rotational and translational energy distributions in the optical
      centrifuge.

PMID- 22457947
TI  - Potential for the detection of molecular complexes and determination of
      interaction geometry by 2DIR: application to protein sciences.
AB  - The ability to detect molecular complexes and determine their geometries is
      crucial to our understanding of all biological phenomena, including protein
      structures and functions. We recently demonstrated that a novel 2DIR technique,
      EVV 2DIR spectroscopy, can be used for this purpose. In this paper, we evaluate
      the potential utility of the method for the analysis of protein composition,
      structure and function. In order to do this we apply computational tools to a
      group of selected biological systems, for which our calculated spectra all showed
      features that can in principle be detected with existing sensitivities. We also
      investigate the possibility of using our technique to detect and analyse hydrogen
      bonded systems through a tyrosine-water model.

PMID- 22457948
TI  - State-resolved THz spectroscopy and dynamics of crystalline peptide-water
      systems.
AB  - Vibrationally state-resolved THz spectra are obtained at cryogenic temperatures
      for three crystalline peptide-water systems that represent different structural
      motifs. The systems include two types of secondary structures and a hydrophobic
      peptide nanopore structure. Almost all of these systems are shown to undergo
      exchange with water at room temperature that alters the hydrogen bonding network
      in ways easily detectable in the THz region at cryogenic temperatures. Stark
      differences are observed in the spectra of model alpha-helical and beta-sheet
      structures upon water removal at hydrophilic binding sites. However, within the
      confined pore of a hydrophobic nanotube, water in the form of helical wires has a
      subtle but significant impact on the phonon modes of the tube. The THz spectra
      are shown to easily distinguish between the different hydration states of the
      system that have been independently characterized by mass change measurements.
      Spectral comparisons with quantum chemical predictions of fully relaxed crystal
      structures confirm the hydration states and give detailed information about the
      free energies associated with dehydration. The vibrational free energies are
      shown to make significant contributions to the overall energy balance of the
      dehydration processes.

PMID- 22457949
TI  - Exploring hydrophobicity by THz absorption spectroscopy of solvated amino acids.
AB  - Although hydrophobicity is a commonly used concept, its microscopic nature,
      particularly in the context of hydration, is not well understood. Here, we
      present a study of hydrophobic and hydrophilic solutes using terahertz (THz)
      spectroscopy and molecular dynamics (MD) simulations. We measured the
      concentration dependent THz absorption (2.1-2.7 THz) of several amino acids and
      peptides in aqueous solution. Experimentally, we find a correlation between the
      change in THz absorption of solvating water and specific properties of the solute
      such as polarity and hydrophobicity. In addition, we studied the effect of
      hydrophobic and hydrophilic model particles on water dynamics by MD simulations.
      We are able to link the vibrational density of states (VDOS) in hydration water
      around the model particles to the experimentally observed change in THz
      absorption of solvated amino acids. We find a stronger increase in THz absorption
      and in the oxygen VDOS of solvating water molecules for the hydrophilic versus
      hydrophobic solutes. The simulations provide us with a microscopic insight into
      the change of the hydration dynamics as induced by hydrophobic and hydrophilic
      solutes. For hydrophobic and hydrophilic model particles a retardation of
      dynamical processes on the picosecond timescale is found, which is more
      pronounced for hydrophilic compared to hydrophobic solutes.

PMID- 22457950
TI  - Single-conformation spectroscopy and population analysis of model gamma-peptides:
      new tests of amide stacking.
AB  - Single-conformation ultraviolet and infrared spectra of a series of model gamma
      peptides are reported, with the goal of providing new tests of amide stacking as
      an amide-amide binding motif. The data also serve to illustrate the power and
      challenges of carrying out single-conformation spectroscopy of neutral molecules
      of this size in the gas phase under jet-cooled conditions. Building on recent
      work on Ac-gamma2-hPhe-NHMe (James et al., J. Am. Chem. Soc., 2009, 131, 14243),
      the effects of derivatization and H2O complexation on amide stacking are studied.
      Ac-gamma2-hPhe-N(Me)2 shows only amide stacked structures, blocking the competing
      position for formation of an amide-amide H-bond. The Ac-gamma2-hPhe-NHMe-H2O
      complex includes structures in which the H2O molecule forms a bridge between the
      two stacked amide planes, retaining and enhancing amide stacking. IR population
      transfer methods are also employed to study the dynamics of photodissociation of
      the amide stacked-H2O complex. Finally, IR ion-gain spectroscopy is introduced as
      a means of recording infrared spectra containing contributions from all
      conformers present, based on IR-induced broadening of the UV absorptions. Its
      role in estimating fractional abundances is tested on Ac-gamma2-hPhe-NHMe.

PMID- 22457951
TI  - Structural studies of biomolecules in the gas phase by chirped-pulse Fourier
      transform microwave spectroscopy.
AB  - Studies of the gas phase structures of biomolecules provide an important
      connection to theoretical methods for modeling large molecular structures. The
      key features of biomolecule structures, such as their conformational flexibility
      and the complexes they form through intermolecular interactions, pose major
      challenges to spectroscopic techniques. Rotationally resolved spectroscopy holds
      the possibility of true structure determination where analysis of the spectra of
      isotopic species provides actual atom positions in the three-dimensional
      structure. Molecular rotational spectroscopy is ideally suited for this type of
      study because it offers high spectral resolution and is generally applicable
      (requiring only a polar molecule). A chirped-pulse Fourier transform microwave
      (CP-FTMW) spectrometer has been optimized for biomolecular spectroscopy. The
      sensitivity of this technique makes it possible to perform heavy atom (13C, 15N,
      18O) structure determination using the natural abundance of the isotopes. The
      performance of the spectrometer is illustrated by obtaining the structure of the
      phenol dimer, a model system that is a challenge for theoretical methods. For
      application to larger biomolecule systems, it is expected that rotational
      spectroscopy alone will face challenges in making structural determinations. The
      scope of problems that can be addressed by rotational spectroscopy can be
      expanded through double-resonance spectroscopy approaches that provide a "second
      dimension" of structural information. A general method to implement laser
      microwave double resonance spectroscopy is described. We also discuss the
      potential for developing low-cost microwave detectors for biomolecular
      spectroscopy that achieve savings by reducing the measurement bandwidth. This
      approach is particularly promising for developing low-frequency CP-FTMW
      spectrometers that are well-suited for large molecule rotational spectroscopy.

PMID- 22457952
TI  - Spectroscopy of mobility-selected biomolecular ions.
AB  - We describe here experiments that combine differential ion mobility, which
      separates conformational isomers of biomolecular ions, with electronic
      spectroscopy in a cold, radio-frequency ion trap. Although the low temperature
      attainable in a cold ion trap greatly simplifies the electronic spectra of large
      molecules, conformational heterogeneity can still be a significant source of
      congestion, complicating spectroscopic analysis. We demonstrate here that using
      differential ion mobility to separate gas-phase peptide conformers before
      injecting them into a cold ion trap allows one to decompose a dense spectrum into
      contributions from different conformational families. In the inverse sense, cold
      ion spectroscopy can be used as a conformation-specific detector for ion
      mobility, allowing one to separate an unresolved peak into contributions from
      different conformational families. The doubly protonated peptide bradykinin
      serves as a good test case for the marriage of these two techniques as it
      exhibits a considerable degree of conformational heterogeneity that results in a
      highly congested electronic spectrum. Our results demonstrate the feasibility and
      advantages of directly coupling ion mobility with spectroscopy and provide a
      diagnostic of conformational isomerization of this peptide after being produced
      in the gas phase by electrospray.

PMID- 22457953
TI  - Time-resolved photoelectron spectroscopy from first principles: excited state
      dynamics of benzene.
AB  - We use the ab initio multiple spawning (AIMS) method to follow the dynamics of
      benzene after excitation to the second singlet excited state (S2). The results
      are validated by comparison to potential energy surfaces including dynamical
      electron correlation effects. Time-resolved photoelectron spectra are computed
      and compared to experimental results. Simulations agree with experiment that
      there are both short-lived and long-lived components of the excited state
      population. We show that these components both originate from quenching through
      the same S2/S1 conical intersection and that the difference between them comes
      from their behavior immediately after decay to S1. This is presumed to be a
      function of the details of the way in which the S2/S1 intersection region is
      accessed; for example, the momentum distribution and the topology of the seam in
      the relevant region.

PMID- 22457954
TI  - The effect of microhydration on ionization energies of thymine.
AB  - A combined theoretical and experimental study of the effect of microhydration on
      ionization energies (IEs) of thymine is presented. The experimental IEs are
      derived from photoionization efficiency curves recorded using tunable synchrotron
      VUV radiation. The onsets of the PIE curves are 8.85 +/- 0.05, 8.60 +/- 0.05,
      8.55 +/- 0.05, and 8.40 +/- 0.05 eV for thymine, thymine mono-, di-, and
      trihydrates, respectively. The computed (EOM-IP-CCSD/cc-pVTZ) AIEs are 8.90,
      8.51, 8.52, and 8.35 eV for thymine and the lowest isomers of thymine mono-, di-,
      and tri-hydrates. Due to large structural relaxation, the Franck-Condon factors
      for the 0 <-- 0 transitions are very small shifting the apparent PIE onsets to
      higher energies. Microsolvation strongly affects IEs of thymine--the addition of
      each water molecule reduces the first vertical IE by 0.10-0.15 eV. The adiabatic
      IE decreases even more (up to 0.4 eV). The magnitude of the effect varies for
      different ionized states and for different isomers. For the ionized states that
      are localized on thymine the dominant contribution to the IE reduction is the
      electrostatic interaction between the delocalized positive charge on thymine and
      the dipole moment of the water molecule.

PMID- 22457955
TI  - Quantitative vibronic coupling calculations. The visible spectrum of
      propadienylidene.
AB  - High-level ab initio calculations that employ the equation-of-motion coupled
      cluster method in the singles, doubles and triples approximation (EOMEE-CCSDT)
      have been used in conjunction with a quasidiabatic ab initio approximation to
      construct a vibronic Hamiltonian for the strongly coupled A1A2 and B1B1 states of
      propadienylidene (CCCH2). Simulations based on the model Hamiltonian reproduce
      all of the major features of the visible absorption spectrum of this molecule,
      with regard to both intensities and band positions, especially in the region that
      is more than 1000 cm(-1) above the B1B1 origin. Despite the fact that a great
      number of individual vibronic levels contribute to each major band in this higher
      energy region, the spectrum is qualitatively similar to that from a Franck-Condon
      treatment, apart from a consequent broadening of the features. By contrast, the
      range from 15 800-16 500 cm(-1), which comprises the B1B1 <-- X1A1 origin, is
      profoundly affected in appearance by the vibronic interaction. The simulations do
      a credible job of accounting for the spectrum in this region, although a thorough
      analysis of all features cannot be made at this time. A combination of ab initio
      calculations, experimental observations and the spectral simulation allows an
      estimate for the position of the (electric dipole forbidden) A1A2 <-- X1A1
      origin: 13 600 +/- 200 cm(-1).

PMID- 22457956
TI  - Charge-transfer and the hydrogen bond: spectroscopic and structural implications
      from electronic structure calculations.
AB  - The absolutely localized molecular orbital (ALMO) model is a fully variational
      approach which permits polarization of molecules interacting in a cluster while
      prohibiting charge-transfer (or dative interactions) between individual
      molecules. The ALMO model can be applied within any density functional theory
      calculation--the B3LYP functional is employed in this work. ALMO DFT calculations
      of observables such as optimized geometry, vibrational frequencies and their
      intensities, and vertical detachment energies are performed for the water dimer,
      the chloride-water complex and the cyanide-water complex. The vibrational spectra
      are obtained both within the harmonic approximation and by quasiclassical
      trajectory simulations. By comparing these ALMO DFT calculations with full DFT
      calculations using precisely the same functional and basis, the role of charge
      transfer on observables in these model hydrogen bonding systems can be assessed.
      The results can be further interpreted using ALMO-based energy decomposition
      analysis, which help to reveal the origin of sensitivity or insensitivity of
      observables to dative interactions. Analysis of the results also suggests that
      the B3LYP functional, while qualitatively adequate, appears to somewhat
      overestimate charge-transfer effects.

PMID- 22457957
TI  - Application of time-independent cumulant expansion to calculation of Franck
      Condon profiles for large molecular systems.
AB  - In this contribution, advantages and disadvantages of the time-independent and
      time-dependent approaches for Franck-Condon profile calculations are discussed
      within the displaced-distorted-rotated harmonic oscillator approximation.
      Particular strengths and prospects of a previously developed time-independent
      cumulant expansion in the calculation of a Franck-Condon profile for UV/Vis
      absorption spectra are demonstrated for the specific case of the S0(1Ag) -->
      S1(1B3u) transition of terrylene at various temperatures.

PMID- 22457958
TI  - Structural characterization of spectroscopic substates in carbonmonoxy
      neuroglobin.
AB  - Relating structure and spectroscopy is fundamental in characterizing the
      conformational dynamics and elucidating function at an atomistic level in
      condensed-phase environments. In particular, the combination of infrared
      spectroscopy and atomistic simulations has provided fundamental insight into
      structural assignments of spectroscopic bands. Infrared spectroscopy and
      Molecular Dynamics (MD) simulations on carbonmonoxy myoglobin (MbCO) were able to
      partially identify three major CO infrared bands (A0, A1 and A3) which are
      related to different conformational substates in the active site of the protein.
      Recently, two similar CO bands were identified from experiments in human
      carbonmonoxy neuroglobin (NgbCO), named N0 and N3. Time-dependent frequency
      changes found in the N0 band and a large variation of relaxation times for these
      bands made the characterization of these substates considerably more difficult
      compared to MbCO. In this work we discuss the structure-spectroscopy relationship
      for three different His64 protonation states in human and murine NgbCO using MD
      simulations and density functional theory (DFT) calculations. The present work
      assigns the N3 band to the His(epsilon)64 tautomer having its side chain in
      hydrogen bonding contact to CO. Frequencies of the corresponding His64H+ and
      His(delta)64 tautomers show characteristic contributions to the N0 band.

PMID- 22457959
TI  - Non-Born-Oppenheimer wavepacket dynamics in polyatomic molecules: vibrations at
      conical intersections in DABCO.
AB  - The role of vibrational dynamics in the vicinity of conical intersections is
      investigated using the first two electronically excited states of 1,4
      diazabicyclo[2,2,2]octane (DABCO) by combining time-resolved photoelectron
      spectroscopy with ab initio computation. Upon resonant excitation of the origin
      band of the short-lived S2 (1E') state, oscillations in the electronic population
      between the S2 (1E') and the S1 (1A'1) electronic states are observed with a
      period of -3 ps. Ab initio computations are employed to characterise these low
      lying excited states, which arise from single excitations into the 3s and 3p
      Rydberg orbitals. Although Rydberg states are generally only weakly coupled,
      DABCO exhibits rapid nonadiabatic dynamics. This implies that strong coupling
      occurs only in the immediate vicinity of a conical intersection, enabling unique
      identification of those vibrations which generate the nonadiabatic transitions.
      To this end, seams of conical intersection are located at energetically relevant
      geometries, engendered by differential distortions of the S1 and S2 potentials
      due to vibronic coupling and a Jahn-Teller-distorted S2 minimum energy point.
      From an analysis of the conical intersection topography, those vibrations leading
      to a maximal modulation of the coupling between the electronic states are readily
      identified. The observed oscillation in the decay of S2 state population is
      thereby assigned to the beat frequency between two sets of vibronic eigenstates
      within the S1 manifold, coherently prepared together with another set at the S2
      band origin, and whose nominal e' degeneracy is lifted due to differential
      coupling to the Jahn-Teller-distorted components of S2.

PMID- 22457960
TI  - Linking photochemistry in the gas and solution phase: S-H bond fission in p
      methylthiophenol following UV photoexcitation.
AB  - Gas-phase H (Rydberg) atom photofragment translational spectroscopy and solution
      phase femtosecond-pump dispersed-probe transient absorption techniques are
      applied to explore the excited state dynamics of p-methylthiophenol connecting
      the short time reactive dynamics in the two phases. The molecule is excited at a
      range of UV wavelengths from 286 to 193 nm. The experiments clearly demonstrate
      that photoexcitation results in S-H bond fission--both in the gas phase and in
      ethanol solution-and that the resulting p-methythiophenoxyl radical fragments are
      formed with significant vibrational excitation. In the gas phase, the recoil
      anisotropy of the H atom and the vibrational energy disposal in the p-MePhS
      radical products formed at the longer excitation wavelengths reveal the operation
      of two excited state dissociation mechanisms. The prompt excited state
      dissociation motif appears to map into the condensed phase also. In both phases,
      radicals are produced in both their ground and first excited electronic states;
      characteristic signatures for both sets of radical products are already apparent
      in the condensed phase studies after 50 fs. No evidence is seen for either solute
      ionisation or proton coupled electron transfer--two alternate mechanisms that
      have been proposed for similar heteroaromatics in solution. Therefore, at least
      for prompt S-H bond fissions, the direct observation of the dissociation process
      in solution confirms that the gas phase photofragmentation studies indeed provide
      important insights into the early time dynamics that transfer to the condensed
      phase.

PMID- 22457961
TI  - Robustness of electronic coherence in the Fenna-Matthews-Olson complex to
      vibronic and structural modifications.
AB  - We present the first two-dimensional electronic spectra of photosynthetic antenna
      complexes bearing modifications to the protein and the chromophores. The vibronic
      structure of the Fenna-Matthews-Olson complex was altered by near-complete
      substitution of 13C for naturally abundant carbon and separately by randomly
      distributed partial deuteration. The structure and arrangement of the
      bacteriochlorophyll a chromophores were modified by deletion of the gene encoding
      the enzyme responsible for reducing the isoprenoid tail of the
      bacteriochlorophylls. Analysis of the time-dependent amplitude of the crosspeak
      corresponding to excitons 1 and 2 indicates that these modifications do not
      affect the frequency or dephasing of the beating observed in this particular
      peak. This result leads us to conclude that this beating indeed arises from
      electronic coherence and not vibrational wavepacket motion. We further conclude
      that the protection of zero-quantum coherences afforded by the protein matrix of
      this photosynthetic complex is not the result of a finely-tuned series of system
      bath interactions perfected by billions of years of evolution but rather a simple
      downstream property of a close arrangement of chromophores within a phonon bath.
      We conclude with a brief discussion of the outstanding questions and possible
      applications of this phenomenon.

PMID- 22457962
TI  - Quantum state resolved velocity-map imaging spectroscopy: a new tool for
      collision dynamics at gas/self-assembled monolayer interfaces.
AB  - The dynamics of HCI scattering from a room-temperature -CH3 terminated self
      assembled monolayer (SAM) is probed via state-resolved spectroscopy coupled to a
      velocity-map imaging (VMI) apparatus. The resulting velocity maps provide new
      insight into the HCl scattering trajectories, revealing for the first time
      correlations between internal and translational degrees of freedom. Velocity maps
      at low J are dominated by signatures of both the incident beam (17.3(3) kcal mol(
      1)) and a room-temperature trapping-desorption component (TD). At high J,
      however, the maps contain a large, continuous feature associated primarily with
      impulsive scattering (IS). Trajectories resulting from these strongly inelastic
      interactions are readily isolated in the map, and provide a new glimpse into
      purely impulsive scattering dynamics. Specifically, within the purely-IS HCI
      region of the velocity maps, the rotational distribution is found to be
      remarkably Boltzmann like, but with a temperature (472 K) significantly higher
      than the SAM surface (300 K). By way of contrast, the translational degree of
      freedom of the impulsively-scattered flux is clearly non-Boltzmann in character,
      with a strong propensity for in-plane scattering in the forward direction, and
      yet still exhibiting out-of-plane velocity distributions reasonably well
      characterized by a temperature of 690 K. These first data establish the prospects
      for a new class of experimental tools aimed at exploring energy transfer and
      reactive scattering events on SAMs, liquid, and metal interfaces with quantum
      state resolved information on correlated internal and translational
      distributions.

PMID- 22457963
TI  - Photoelectron-photofragment coincidence studies of NO(-)-X clusters (X = H2O,
      CD4).
AB  - The dissociative photodetachment of NO-(H2O)and NO-(CD4) anion clusters was
      studied at 775 nm (1.60 eV) using photoelectron-photofragment coincidence
      spectroscopy. The correlation between the photoelectron and photodetached neutral
      spectra indicates vibrational excitation in the recoiling NO neutral fragments
      from NO-(H2O), with a progression consistent with vibrational excitation up to
      upsilon(NO) = 3 in the products. The correlation remains when D2O is substituted
      for H2O, implying the NO vibrational mode plays a role in the dissociation
      coordinate of the complex. In contrast, no correlation was observed between
      photoelectron kinetic energy and kinetic energy release from NO-(CD4).
      Consideration of the maximum available kinetic energy allows the binding energies
      to be detemined as 0.57 and 0.07 eV for NO-(H2O) and NO-(CD4), respectively.

PMID- 22457964
TI  - The structure and terahertz dynamics of water confined in nanoscale pools in salt
      solutions.
AB  - The behaviour of liquid water below its melting point is of great interest as it
      may hold clues to the properties of normal liquid water and of water in and on
      the surfaces of biomolecules. A second critical point, giving rise to a
      polyamorphic transition between high and low density water, may be hidden in the
      supercooled region but cannot be observed directly. Here it is shown that water
      can be locked up in nano-pools or worm-like structures using aqueous LiCl salt
      solutions and can be studied with terahertz spectroscopies. Very high dynamic
      range ultrafast femtosecond optical Kerr effect (OKE) spectroscopy is used to
      study the temperature-dependent behaviour of water in these nano-pools on
      timescales from 10 fs to 4 ns. These experiments are complemented by temperature
      dependent nuclear magnetic resonance (NMR) diffusion measurements, concentration
      dependent Fourier-transform infrared (FTIR) measurements, and temperature
      dependent rheology. It is found that liquid water in the nanoscale pools
      undergoes a fragile-to-strong transition at about 220 K associated with a sharp
      increase in the inhomogeneity of translational dynamics.

PMID- 22457965
TI  - Frontiers in spectroscopy.
AB  - We review the frontiers of spectroscopy from a historical perspective, starting
      with the development of atomic spectroscopy about 150 years ago, followed by some
      comments on selected previous Faraday Discussions. As the spectrum of frontiers
      at the Faraday Discussion 150 is very broad, we give only a brief survey
      providing a map of the various frontiers approached today. This is followed by an
      exemplary discussion of one particular frontier towards the spectroscopic
      detection of symmetry violations in fundamental physics. In particular the
      understanding of parity violation in chiral molecules has recently made great
      progress. We briefly describe the advances made in recent decades as well as the
      current status of theory and experiments in this exciting field of research. We
      conclude with an outlook on open questions and frontiers of the future in
      spectroscopy.

PMID- 22457966
TI  - A conversation with Karl K. Turekian. Interview by J Kirk Cochran.

PMID- 22457967
TI  - Climate change impacts on marine ecosystems.
AB  - In marine ecosystems, rising atmospheric CO2 and climate change are associated
      with concurrent shifts in temperature, circulation, stratification, nutrient
      input, oxygen content, and ocean acidification, with potentially wide-ranging
      biological effects. Population-level shifts are occurring because of
      physiological intolerance to new environments, altered dispersal patterns, and
      changes in species interactions. Together with local climate-driven invasion and
      extinction, these processes result in altered community structure and diversity,
      including possible emergence of novel ecosystems. Impacts are particularly
      striking for the poles and the tropics, because of the sensitivity of polar
      ecosystems to sea-ice retreat and poleward species migrations as well as the
      sensitivity of coral-algal symbiosis to minor increases in temperature.
      Midlatitude upwelling systems, like the California Current, exhibit strong
      linkages between climate and species distributions, phenology, and demography.
      Aggregated effects may modify energy and material flows as well as biogeochemical
      cycles, eventually impacting the overall ecosystem functioning and services upon
      which people and societies depend.

PMID- 22457968
TI  - The physiology of global change: linking patterns to mechanisms.
AB  - Global change includes alterations in ocean temperature, oxygen availability,
      salinity, and pH, abiotic variables with strong and interacting influences on the
      physiology of all taxa. Physiological stresses resulting from changes in these
      four variables may cause broad biogeographic shifts as well as localized changes
      in distribution in mosaic habitats. To elucidate these causal linkages, I address
      the following questions: What types of physiological limitations can alter
      species' distributions and, in cases of extreme stress, cause extinctions? Which
      species are most threatened by these physiological challenges--and why? How do
      contents of genomes establish capacities to respond to global change, notably in
      the case of species that have evolved in highly stable habitats? How fully can
      phenotypic acclimatization offset abiotic stress? Can physiological measurements,
      including new molecular ("-omic") approaches, provide indices of the degree of
      sublethal stress an organism experiences? And can physiological evolution keep
      pace with global change?

PMID- 22457969
TI  - Shifting patterns of life in the Pacific Arctic and sub-Arctic seas.
AB  - Recent changes in the timing of sea ice formation and retreat, along with
      increasing seawater temperatures, are driving shifts in marine species
      composition that may signal marine ecosystem reorganization in the Pacific Arctic
      sector. Interannual variability in seasonal sea ice retreat in the northern
      Bering Sea has been observed over the past decade; north of the Bering Strait,
      the Chukchi Sea ecosystem has had consistent earlier spring sea ice retreat and
      later fall sea ice formation. The latitudinal gradient in sea ice persistence,
      water column chlorophyll, and carbon export to the sediments has a direct impact
      on ecosystem structure in this Arctic/sub-Arctic complex. Large-scale decadal
      patterns in the benthic biological system are driven by sea ice extent,
      hydrographic forcing, and export production that influences benthic processes.
      Shifts in species composition and northward faunal range expansions indicate a
      changing system. The shifting patterns of life and change in key biological
      processes have the potential for a system-wide reorganization of the marine
      ecosystem.

PMID- 22457970
TI  - Understanding continental margin biodiversity: a new imperative.
AB  - Until recently, the deep continental margins (200-4,000 m) were perceived as
      monotonous mud slopes of limited ecological or environmental concern. Progress in
      seafloor mapping and direct observation now reveals unexpected heterogeneity,
      with a mosaic of habitats and ecosystems linked to geomorphological, geochemical,
      and hydrographic features that influence biotic diversity. Interactions among
      water masses, terrestrial inputs, sediment diagenesis, and tectonic activity
      create a multitude of ecological settings supporting distinct communities that
      populate canyons and seamounts, high-stress oxygen minimum zones, and methane
      seeps, as well as vast reefs of cold corals and sponges. This high regional
      biodiversity is fundamental to the production of valuable fisheries, energy, and
      mineral resources, and performs critical ecological services (nutrient cycling,
      carbon sequestration, nursery and habitat support). It is under significant
      threat from climate change and human resource extraction activities. Serious
      actions are required to preserve the functions and services provided by the deep
      sea settings we are just now getting to know.

PMID- 22457971
TI  - Nutrient ratios as a tracer and driver of ocean biogeochemistry.
AB  - Microbial life in the ocean contains immense taxonomic and physiological
      diversity, yet its collective activity yields global cycles of the major
      biolimiting elements N and P that are tightly linked. Moreover, the availability
      of N and P in seawater is closely matched to the metabolic demands of "average"
      plankton, as if plankton composition and the oceanic nutrient reservoirs were
      mutually influenced. These simple observations have broad implications for the
      function of nutrient cycles within the Earth system, which can operate either as
      a biological homeostat that buffers ocean fertility against large changes or as
      an amplifier of climate perturbations, by alleviating or exacerbating the
      nutrient limitation of biological productivity and ocean C storage. A mechanistic
      understanding of these observations and dynamics must draw upon diverse fields,
      from physiology and evolution to physical oceanography and paleoceanography, and
      must account for processes spanning a wide range of spatial and temporal scales.
      Here we summarize this understanding from the perspective of the nutrient
      distributions themselves and their changes over time. We offer a synthesis view
      in which ocean circulation communicates the resource constraints of
      stoichiometrically distinct planktonic biomes across large spatial scales,
      allowing geochemical constancy to emerge from rich biological diversity.

PMID- 22457972
TI  - Progress in understanding harmful algal blooms: paradigm shifts and new
      technologies for research, monitoring, and management.
AB  - The public health, tourism, fisheries, and ecosystem impacts from harmful algal
      blooms (HABs) have all increased over the past few decades. This has led to
      heightened scientific and regulatory attention, and the development of many new
      technologies and approaches for research and management. This, in turn, is
      leading to significant paradigm shifts with regard to, e.g., our interpretation
      of the phytoplankton species concept (strain variation), the dogma of their
      apparent cosmopolitanism, the role of bacteria and zooplankton grazing in HABs,
      and our approaches to investigating the ecological and genetic basis for the
      production of toxins and allelochemicals. Increasingly, eutrophication and
      climate change are viewed and managed as multifactorial environmental stressors
      that will further challenge managers of coastal resources and those responsible
      for protecting human health. Here we review HAB science with an eye toward new
      concepts and approaches, emphasizing, where possible, the unexpected yet
      promising new directions that research has taken in this diverse field.

PMID- 22457973
TI  - Thin phytoplankton layers: characteristics, mechanisms, and consequences.
AB  - For over four decades, aggregations of phytoplankton known as thin layers have
      been observed to harbor large amounts of photosynthetic cells within narrow
      horizontal bands. Field observations have revealed complex linkages among thin
      phytoplankton layers, the physical environment, cell behavior, and higher trophic
      levels. Several mechanisms have been proposed to explain layer formation and
      persistence, in the face of the homogenizing effect of turbulent dispersion. The
      challenge ahead is to connect mechanistic hypotheses with field observations to
      gain better insight on the phenomena that shape layer dynamics. Only through a
      mechanistic understanding of the relevant biological and physical processes can
      we begin to predict the effect of thin layers on the ecology of phytoplankton and
      higher organisms.

PMID- 22457974
TI  - Jellyfish and ctenophore blooms coincide with human proliferations and
      environmental perturbations.
AB  - Human populations have been concentrated along and exploiting the coastal zones
      for millennia. Ofregions with the highest human impacts on the oceans (Halpern et
      al. 2008), 6 of the top 10 have recently experienced blooms or problems with
      jellies. I review the time lines of human population growth and their effects on
      the coastal environment. I explore evidence suggesting that human activities-
      specifically, seafood harvest, eutrophication, hard substrate additions,
      transport ofnonindigenous species, aquaculture, and climate change--may benefit
      jelly populations. Direct evidence is lacking for most of these factors; however,
      numerous correlations show abundant jellies in areas with warm temperatures and
      low forage fish populations. Jelly populations fluctuate in approximately 10- and
      approximately 20-year cycles in concert with solar and climate cycles. Global
      warming will provide a rising baseline against which climate cycles will cause
      fluctuations in jelly populations. The probable acceleration of anthropogenic
      effects may lead to further problems with jellies.

PMID- 22457975
TI  - Benthic foraminiferal biogeography: controls on global distribution patterns in
      deep-water settings.
AB  - Benthic foraminifera, shell-bearing protists, are familiar from geological
      studies. Although many species are well known, undescribed single-chambered forms
      are common in the deep sea. Coastal and sublittoral species often have restricted
      distributions, but wide ranges are more frequent among deep-water species,
      particularly at abyssal depths. This probably reflects the transport of tiny
      propagules by currents across ocean basins that present few insurmountable
      barriers to dispersal, combined with slow rates of evolution. Undersampling of
      the vast deep-sea habitat, however, makes it very difficult to establish the
      ranges of less common foraminiferal species, and endemism may be more prevalent
      than currently realized. On continental slopes, some species have restricted
      distributions, but wide-ranging bathyal species that exhibit considerable
      morphological variation are more common. This may be linked to the greater
      heterogeneity of continental slopes compared with oceans basins. Improved
      knowledge of deep-sea foraminiferal biogeography requires sound morphology-based
      taxonomy combined with molecular genetic studies.

PMID- 22457976
TI  - Plankton and particle size and packaging: from determining optical properties to
      driving the biological pump.
AB  - Understanding pelagic ecology and quantifying energy fluxes through the trophic
      web and from the surface to the deep ocean requires the ability to detect and
      identify all organisms and particles in situ and in a synoptic manner. An
      idealized sensor should observe both the very small living or dead particles such
      as picoplankton and detritus, respectively, and the large particles such as
      aggregates and meso- to macroplankton. Such an instrument would reveal an
      astonishing amount and diversity of living and nonliving particles present in a
      parcel of water. Unfortunately such sensors do not exist. However, complex
      interactions constrain the space, temporal, and size distributions of these
      objects in such ways that general rules can be inferred from the measurement of
      their optical properties. Recent technological developments allow for the in situ
      measurement of the optical properties and size distributions of particles and
      plankton in a way such that synoptic surveys are possible. This review deals with
      particle and plankton size distributions (PSDs) as well as how particles'
      geometry and nature affect their optical properties. Finally, we propose the
      integration of the PSD into size-structured mathematical models of biogeochemical
      fluxes.

PMID- 22457977
TI  - Overturning in the North Atlantic.
AB  - The global overturning of ocean waters involves the equatorward transport of
      cold, deep waters and the poleward transport of warm, near-surface waters. Such
      movement creates a net poleward transport of heat that, in partnership with the
      atmosphere, establishes the global and regional climates. Although oceanographers
      have long assumed that a reduction in deep water formation at high latitudes in
      the North Atlantic translates into a slowing of the ocean's overturning and hence
      in Earth's climate, observational and modeling studies over the past decade have
      called this assumed linkage into question. The observational basis for linking
      water mass formation with the ocean's meridional overturning is reviewed herein.
      Understanding this linkage is crucial to efforts aimed at predicting the
      consequences of the warming and freshening of high-latitude surface waters to the
      climate system.

PMID- 22457978
TI  - The wind- and wave-driven inner-shelf circulation.
AB  - The inner continental shelf, which spans water depths ofa few meters to tens of
      meters, is a dynamically defined region that lies between the surf zone (where
      waves break) and the middle continental shelf (where the along-shelf circulation
      is usually in geostrophic balance). Many types of forcing that are often
      neglected over the deeper shelf-such as tides, buoyant plumes, surface
      gravitywaves, and cross-shelfwind stress-drive substantial circulations over the
      inner shelf. Cross-shelf circulation over the inner shelf has ecological and
      geophysical consequences: It connects the shore to the open ocean by transporting
      pollutants, larvae, phytoplankton, nutrients, and sediment. This review of
      circulation and momentum balances over the inner continental shelf contrasts
      prior studies, which focused mainly on the roles of along-shelfwind and pressure
      gradients, with recent understanding of the dominant roles of cross-shelf wind
      and surface gravity waves.

PMID- 22457979
TI  - Serpentinite mud volcanism: observations, processes, and implications.
AB  - Large serpentinite mud volcanoes form on the overriding plate of the Mariana
      subduction zone. Fluids from the descending plate hydrate (serpentinize) the
      forearc mantle and enable serpentinite muds to rise along faults to the seafloor.
      The seamounts are direct windows into subduction processes at depths far too deep
      to be accessed by any known technology. Fluid compositions vary with distance
      from the trench, signaling changes in chemical reactions as temperature and
      pressure increase. The parageneses of rocks in the mudflows permits us to
      constrain the physical conditions of the decollement region. If eruptive episodes
      are related to seismicity, seafloor observatories at these seamounts hold the
      potential to capture a subduction event and trace the effects of eruption on the
      biological communities that the slab fluids support, such as extremophile
      Archaea. The microorganisms that inhabit this high-pH, extreme environment
      support their growth by utilizing chemical constituents present in the slab
      fluids. Some researchers now contend that the serpentinization process itself may
      hold the key to the origin of life on Earth.

PMID- 22457980
TI  - Marine microgels.
AB  - The ocean plays a critical role in global carbon cycling: it handles half of the
      global primary production, yielding the world's largest stock of reduced organic
      carbon (ROC) that supports one of the world's largest biomasses. However, the
      mechanisms whereby ROC becomes mineralized remain unresolved. This review focuses
      on laboratory and field observations that dissolved organic carbon (DOC) self
      assembles, forming self-assembled microgels (SAGs). Self-assembly has
      approximately10% yield, generating an estimated global seawater SAG budget of
      approximately 10(16) g C. Transects at depths of 10-4,000 m reveal concentrations
      of approximately 10(6) to approximately 3 x 10(12) SAG L(-1), respectively,
      forming an estimated ROC stock larger than the global marine biomass. Because
      hydrogels have approximately 1% solids (10 g L(-1)), whereas seawater DOC reaches
      approximately 10(-3) g L(-1), SAGs contain approximately 10(4) more bacterial
      substrate than seawater. Thus, microgels represent an unsuspected and huge micron
      level ocean patchiness that could profoundly influence the passage of DOC through
      the microbial loop, with ramifications that may scale to global cycles of
      bioactive elements.

PMID- 22457981
TI  - The fate of terrestrial organic carbon in the marine environment.
AB  - Understanding the fate of terrestrial organic carbon (Corg) delivered to oceans
      by rivers is critical for constraining models of biogeochemical cycling and Earth
      surface evolution. Corg fate is dependent on both intrinsic characteristics
      (molecular structure, matrix) and the environmental conditions to which fluvial
      Corg is subjected. Three distinct patterns are evident on continental margins
      supplied by rivers: (a) high-energy, mobile muds with enhanced oxygen exposure
      and efficient metabolite exchange have very low preservation of both terrestrial
      and marine Corg (e.g., Amazon subaqueous delta); (b) low-energy facies with
      extreme accumulation have high Corg preservation (e.g., Ganges-Brahmaputra); and
      (c) small, mountainous river systems that sustain average accumulation rates but
      deliver a large fraction of low-reactivity, fossil Corg in episodic events have
      the highest preservation efficiencies. The global patterns of terrestrial Corg
      preservation reflect broadly different roles for passive and active margin
      systems in the sedimentary Corg cycle.

PMID- 22457982
TI  - Marine viruses: truth or dare.
AB  - Over the past two decades, marine virology has progressed from a curiosity to an
      intensely studied topic of critical importance to oceanography. At concentrations
      of approximately 10 million viruses per milliliter of surface seawater, viruses
      are the most abundant biological entities in the oceans. The majority of these
      viruses are phages (viruses that infect bacteria). Through lysing their bacterial
      hosts, marine phages control bacterial abundance, affect community composition,
      and impact global biogeochemical cycles. In addition, phages influence their
      hosts through selection for resistance, horizontal gene transfer, and
      manipulation of bacterial metabolism. Recent work has also demonstrated that
      marine phages are extremely diverse and can carry a variety of auxiliary
      metabolic genes encoding critical ecological functions. This review is structured
      as a scientific "truth or dare," revealing several well-established "truths"
      about marine viruses and presenting a few "dares" for the research community to
      undertake in future studies.

PMID- 22457983
TI  - The rare bacterial biosphere.
AB  - All communities are dominated by a few species that account for most of the
      biomass and carbon cycling. On the other hand, a large number of species are
      represented by only a few individuals. In the case of bacteria, these rare
      species were until recently invisible. Owing to their low numbers, conventional
      molecular techniques could not retrieve them. Isolation in pure culture was the
      only way to identify some of them, but current culturing techniques are unable to
      isolate most of the bacteria in nature. The recent development of fast and cheap
      high-throughput sequencing has begun to allow access to the rare species. In the
      case of bacteria, the exploration of this rare biosphere has several points of
      interest. First, it will eventually produce a reasonable estimate of the total
      number of bacterial taxa in the oceans; right now, we do not even know the right
      order of magnitude. Second, it will answer the question of whether "everything is
      everywhere." Third, it will require hypothesizing and testing the ecological
      mechanisms that allow subsistence of many species in low numbers. And fourth, it
      will open an avenue of research into the immense reserve of genes with potential
      applications hidden in the rare biosphere.

PMID- 22457984
TI  - Marine protistan diversity.
AB  - Protists have fascinated microbiologists since their discovery nearly 350 years
      ago. These single-celled, eukaryotic species span an incredible range of sizes,
      forms, and functions and, despite their generally diminutive size, constitute
      much of the genetic diversity within the domain Eukarya. Protists in marine
      ecosystems play fundamental ecological roles as primary producers, consumers,
      decomposers, and trophic links in aquatic food webs. Much of our knowledge
      regarding the diversity and ecological activities of these species has been
      obtained during the past half century, and only within the past few decades have
      hypotheses depicting the evolutionary relationships among the major clades of
      protists attained some degree of consensus. This recent progress is attributable
      to the development of genetic approaches, which have revealed an unexpectedly
      large diversity of protists, including cryptic species and previously undescribed
      clades of protists. New genetic tools now exist for identifying protistan species
      of interest and for reexamining long-standing debates regarding the biogeography
      of protists. Studies of protistan diversity provide insight regarding how species
      richness and community composition contribute to ecosystem function. These
      activities support the development of predictive models that describe how
      microbial communities will respond to natural or anthropogenically mediated
      changes in environmental conditions.

PMID- 22457985
TI  - Marine fungi: their ecology and molecular diversity.
AB  - Fungi appear to be rare in marine environments. There are relatively few marine
      isolates in culture, and fungal small subunit ribosomal DNA (SSU rDNA) sequences
      are rarely recovered in marine clone library experiments (i.e., culture
      independent sequence surveys of eukaryotic microbial diversity from environmental
      DNA samples). To explore the diversity of marine fungi, we took a broad selection
      of SSU rDNA data sets and calculated a summary phylogeny. Bringing these data
      together identified a diverse collection of marine fungi, including sequences
      branching close to chytrids (flagellated fungi), filamentous hypha-forming fungi,
      and multicellular fungi. However, the majority of the sequences branched with
      ascomycete and basidiomycete yeasts. We discuss evidence for 36 novel marine
      lineages, the majority and most divergent of which branch with the chytrids. We
      then investigate what these data mean for the evolutionary history of the Fungi
      and specifically marine-terrestrial transitions. Finally, we discuss the roles of
      fungi in marine ecosystems.

PMID- 22457987
TI  - [Passive correction of an anterior open bite related to non-nutritive sucking
      habits: report of a case].
AB  - The term anterior open bite refers to a vertical space between the upper and
      lower front teeth in maximum intercuspation. This malocclusal trait can accompany
      many malocclusions of the Angle's classification. Two types of anterior open bite
      have been described: skeletal and dental open bite. The latter may have Non
      Nutritive Sucking Habits (NNSH) as causal factor and is deemed to aggravate
      without treatment. This article presents an interceptive approach based on the
      use of a fixed passive appliance interfering with sucking habit. It consists of a
      crib soldered to bands adjusted to the maxillary first permanent or temporary
      second molars. The device was globally well accepted by the patient and has been
      effective in breaking the sucking habit and subsequently in closing the bite
      after only 5 month. When psychological approach is not effective, a fixed
      deterrent device may be recommended for weaning children off nonnutritive sucking
      habits.

PMID- 22457986
TI  - Genomic insights into bacterial DMSP transformations.
AB  - Genomic and functional genomic methods applied to both model organisms and
      natural communities have rapidly advanced understanding of bacterial
      dimethylsulfoniopropionate (DMSP) degradation in the ocean. The genes for the two
      main pathways in bacterial degradation, routing DMSP to distinctly different
      biogeochemical fates, have recently been identified. The genes dmdA, -B, -C, and 
      D mediate the demethylation of DMSP and facilitate retention of carbon and sulfur
      in the marine microbial food web. The genes dddD, -L, -P, -Q, -W, and -Y mediate
      the cleavage of DMSP to dimethylsulfide (DMS), with important consequences for
      ocean-atmosphere sulfur flux. In ocean metagenomes, sufficient copies of these
      genes are present for approximately 60% of surface ocean bacterial cells to
      directly participate in DMSP degradation. The factors that regulate these two
      competing pathways remain elusive, but gene transcription analyses of natural
      bacterioplankton communities are making headway in unraveling the intricacies of
      bacterial DMSP processing in the ocean.

PMID- 22457988
TI  - Entoconulid (cusp 6), metaconulid (cusp 7), post-metaconulid and pre-entoconulid
      expression on permanent mandibular first molar in the living Jordanian population
      and inter-trait interactions.
AB  - OBJECTIVES: To determine the frequency of expression and sexual dimorphism of the
      following dental morphological traits on the permanent mandibular first molar
      (LM1) in the living Jordanians: Entoconulid (cusp 6; tuberculum sextum),
      metaconulid (cusp 7, tuberculum intermedium), post-metaconulid and pre
      entoconulid (entostylid) traits. In addition, to analyze inter-trait interactions
      whenever possible was one of the aims. METHODS: Three hundred sixty school
      children (176 males, 184 females, ages 15.5 +/- 0.4 years) from the middle of
      Jordan were involved. Impressions for the mandibular dental arches were taken,
      and dental casts were produced in 2009. The above-mentioned traits were observed.
      Z-value test between two proportions and nonparametric correlation analysis were
      used for data analysis. RESULTS: Cusp 7 on LM1 was found in 15.83 %, while cusp 6
      on this tooth was found in 21.67% of the examined students. In comparison, both
      post-metaconulid and pre-entoconulid traits were found to be absent on LM1 in all
      observed subjects. Nonparametric correlation analysis revealed weak negative and
      statistically insignificant association between the expression of cusp 6 and 7 on
      LM1 among the living Jordanians. CONCLUSION: Both cusp 6 and cusp 7 on LM1 are
      expressed in a relatively higher rate among the living Jordanian Arabs than other
      studied Western Eurasians, suggesting a significant gene flow from Sub-Saharan
      Africans and Mongolians to the Middle East. In addition, the insignificant weak
      correlation between cusp 6 and 7 on LM1 suggests that these two dental
      morphological traits are both genetically and phenotypically independent.

PMID- 22457989
TI  - [Fluoride levels in commercial dentifrices and drinking water in Algeria].
AB  - More and more scientific evidence show that fluorides have a cariostatic action
      to the plaque-saliva-tooth interface during cariogenous dissolution. Fluorides
      slow down demineralization and enhance remineralization. Their action is optimal,
      in the oral environment, when used at low concentrations on a continuous basis.
      The use of the fluorinated toothpastes during brushing of the teeth is a simple,
      rational method of daily topics application of fluorine, largely used in the
      context of prevention of dental caries and which can even be regarded as a public
      health measure. The water ingestion fluorinated represents itself an excellent
      average of the local application of fluorine. Our work concerned a quantitative
      study of fluorine in toothpaste and drinking water, and comparative between the
      local product and the imported one for the toothpastes, and the mineral water and
      public supply. The standard method of fluorine based on the potentiometry and
      distillation has shown that 50% of the tested toothpastes contain adequate
      concentration so that a product of dental care fights against decay. The Tlemcen
      tap water contains acceptable fluorine content, but the mineral water, with an
      excessive contribution, can cause fluorose. Of this, we can deduce that a topical
      application of a suitable quantity of fluorine on a daily basis in accordance
      with the precautions is not only the prevention of dental caries, but also to
      stabilize it if it already exists.

PMID- 22457990
TI  - [The effect of autoclave sterilization on the surface properties of orthodontic
      brackets after fitting in the mouth].
AB  - Repeated sterilizations of the orthodontic bands, after fitting in mouth, are
      likely to involve modifications of their surface properties. Through this study
      we have tried to observe the effect of sterilization by autoclave on the surface
      of the orthodontic bands, as well as the contribution of the use of ultrasound in
      the chain of sterilization. The sample was composed of 30 orthodontic bands
      divided into 5 groups: a group of new bands (witnesses) and 4 groups having
      undergone respectively 1 cycle, 3 cycles, 5 cycles and 7 cycles of autoclave
      sterilization according to the World Health Organization recommendations. For
      half of each group bands, ultrasonic cleaning has not been provided. The scanning
      electron microscopy with the elementary microanalysis by X-rays was used for the
      investigation of surface. At the exam, new bands showed surface irregularities
      probably due to manufacturing procedures. And the bands, without ultrasonic
      cleaning, showed the presence of contamination and discolourations. Moreover,
      there were no modifications on the surface of the bands cleaned by ultrasounds
      before sterilization. The presence of surface irregularities associated with
      deposits observed on the bands surface, may be the site of bio corrosion by
      contributing bio film accumulation. The stay duration of the orthodontic bands in
      mouth, during orthodontic treatment, is important. So the effect of sterilization
      on the surface of the orthodontic bands must encourage other scientific research
      to determine the long term effects of sterilization which remains an essential
      process in our daily practice.

PMID- 22457991
TI  - Traditional and emerging oral health practices in parts of Nigeria.
AB  - OBJECTIVE: The purpose of this study was to document the beliefs and perceptions
      and emerging oral health care practices in parts of Nigeria. METHODS: A
      descriptive study, based in four different locations that were selected to
      reflect urban-rural and geographical spread, was conducted. Focus group
      discussions and in-depth interviews were conducted among representative groups
      and significant gatekeepers in the study areas. The discussions focused on oral
      health problems frequently encountered in the communities, their dietary and
      snacking habits as well as the dental remedies commonly employed by the people
      for prophylactic and therapeutic purposes. RESULTS: It was revealed that in both
      rural and urban low- to- middle socio-economic classes, periodontitis was the
      commonest dental problem in adults, while dental caries in children appeared to
      be also a cause for concern especially in northern Nigeria and the urban south.
      Most adults ate the local staple carbohydrate diets, however large quantities of
      cariogenic snacks were reported to be consumed. Chewing sticks and locally
      prepared toothpastes ranked prominent among the tooth cleaning implements, but
      many in the cities used toothbrushes. Various dental care remedies were employed
      ranging from warm saline wash to herbal preparations, antibiotics and battery
      water. In communities studied, the belief in ill defined "worms" as causative
      agents of all oral health problems was very firm. Consultation with traditional
      oral healthcare practitioners was a practice commonly observed in all study
      sites. CONCLUSION: This study has highlighted specific areas for intervention in
      disease prevention and oral health promotion in Nigeria.

PMID- 22457993
TI  - Science convicting the innocent.
AB  - This paper focuses on the dangers of scientific evidence in criminal cases. The
      general reliability of scientific evidence is reviewed. Second, cases are
      evaluated thus tracing the development of the rules set out for the admissibility
      of scientific expert evidence. Third, cases are analyzed and the existing rules
      are criticized; this analysis grounds several proposed changes set forth as a
      protection for an accused person from possible dangers accompanied with
      scientific evidence. And finally, this paper proposes that the trial judge should
      exercise more active and comprehensive discretion to exclude potentially
      dangerous scientific evidence. Instead of assessing threshold reliability
      questions, the trial judge should determine the actual reliability of scientific
      evidence under the ad-hoc circumstances of the particular case before him. The
      trial judge should then determine if the scientific evidence meets the new tests,
      as proposed in this paper, for scientific admissibility, depending on whether the
      defense or the prosecution relies on science and how close science is to the
      ultimate issue of guilt or innocence. In judge-rule trails, judges must rule on
      the scientifically more accurate theory, but not on the more convincing expert.

PMID- 22457992
TI  - [A comparative study of the transverse dimensions of the dental arches between
      Class I dental occlusion and Class II1 and Class II2 malocclusions].
AB  - The purpose of this work was to compare transverse dimensions of the maxillary
      and mandibular arches in the canine and molar region between three groups of
      patients: the first group had an occlusion in class II division 1, the second one
      a dental class II division 2 and the third one, a class I bite. Our sample is
      composed of 94 patients, with an average age of 20 +/- 3 years: 31 patients
      presented a class I occlusion, 33 a class III1 and 30 cases presented a dental
      class II2. For this study, we measured, on the maxillary and mandibular dental
      casts of each patient, the intercanine and intermolar canine (central inter
      fossa). Comparison of variables was conducted using the variance analysis ANOVA;
      the selected post-hoc test is the Bonferrroni test. On the basis of our study, we
      can get the following results: Maxillary intercanine distance is narrower in
      class II1 compared to class II2 of 2 mm "p < 0.05". Mandibular intercanine
      distance is narrower in class III1 compared to class II2 of 1, 3 mm "p < 0.05".
      Maxillary intermolar distance (inter fossa) is narrower in class II1 compared to
      class I of 2, 2 mm "p < 0.05".

PMID- 22457994
TI  - Advance directives in the clinical ethics context: an African perspective.
AB  - In this paper I examine issues associated with advance directives and the impact
      these issues have on people's lives based on their value systems. I ague from an
      African perspective, where I defend the view that competent persons ought to be
      allowed to decide on medical interventions they want (or do not want) should they
      become incompetent. My arguments are derived from the idea of African concepts of
      death, dying and belief in ancestral realm. The principle of collective
      autonomous decision is used to explain how decisions on advance directives to
      reject a medical intervention can be implemented in the African context.

PMID- 22457995
TI  - How do we care for our future caregivers? Rethinking education in bioethics with
      regard to professionalism and institutions.
AB  - BACKGROUND: Bioethics is an integral part of most medical curricula. It
      complements medical skills training to help future caregivers make morally good
      decisions in their encounters with patients. Principle-based concepts are
      commonly regarded as the mainstream approach to bioethics in today's world.
      However, despite its clear merits, principlism alone is not sufficient for
      educating future caregivers. Hence, additional perspectives of health care
      education are required and will be taken into account in this paper. OBJECTIVES:
      Two shortcomings of typical health care training must be addressed: insufficient
      consideration of the nature of the health care profession and of institutional
      requirements. Notions and relevance of professionalism in health care have been
      intensively discussed in recent years. In this paper, I argue that a caring
      understanding of professionalism is essential for good quality care for the
      patient and for the physicians themselves. With reference to the ethics of care,
      the scope of caring professionalism and its implications for health care
      education are considered and placed within an analytical framework that combines
      the individual and the institutional context of health care. CONCLUSIONS: To
      educate our future caregivers, we must address aspects of professionalism more
      intensively in medical and nursing schools, and even more so during residencies.
      This is not just a task of training in knowledge or competencies, but also
      involves the character formation of the individual and the whole organization.
      Rethinking health care education from this perspective will allow us to answer
      the question 'How do we care for our future caregivers?' with an easier
      conscience.

PMID- 22457996
TI  - Research ethics committees and community values: Devlin, Dworkin, Hart and
      beyond.
AB  - Two fundamental requirements ought to be met in any selection to research ethics
      committees: (i) professional scientific competence, and (ii) the understanding of
      moral values which prevail in any community. The question is: Should the verdicts
      of research ethics committees be based on community values? This article
      critically examines theories of community as were propounded by Devlin, Dworkin
      and Hart in answer to this question. It is argued that community values are
      complementary rather than conflicting, and that Dworkin's theory of community
      provides an analytical framework for research ethics on the new genetic
      technologies. Finally, it is submitted that the verdicts of research ethics
      committees should be based on community values.

PMID- 22457997
TI  - Autopsy of 15 clinical death cases: relationship between medicine and
      jurisprudence.
AB  - OBJECTIVE: Autopsy has been performed on the 15 clinical death cases with
      complete data, through which the relationship between medicine and jurisprudence
      will be analyzed. METHODS: The data of the diagnosis and treatment about the 15
      clinical death cases were analyzed in comparison with the results of the autopsy.
      RESULTS: Six cases were misdiagnosed, five cases mistreated, four cases with
      multi-factors. With the help of autopsy the twelve cases were not identified as
      malpractice, which were accredited as medical fault. CONCLUSIONS: The autopsy is
      playing a unique role in defining the cause of death. It can clarify the medical
      responsibility and resolve the medical dispute.

PMID- 22457998
TI  - Medicinal products in the European Union--between harmonization and divergence.
AB  - The rules governing the manufacture and trade in medicinal products in the
      European Union are, to a large extent, harmonized covering almost the entire life
      cycle of a medicinal product, starting from the conduct of clinical trials
      (Directive 2001/20, 2005/28), through manufacture (Directive 2003/94),
      registration, distribution and pharmacovigilance (Directive 2001/83) to the
      principles concerning pricing and reimbursement (Directive 89/105). A unified
      registration procedure has been established with respect to highly innovative
      medicinal products (Regulation 726/2004). There is also abundant case law of the
      European Court of Justice concerning medicinal products. The harmonization both
      judicial and legislative--took place in spite of the lack of explicit competence
      of the EU as regards healthcare and was based to a large extent on the provisions
      of economic nature, whose aim was to ensure the unfettered functioning of the
      internal market. In spite of those harmonization efforts, national rules
      governing pharmaceuticals are still to a large extent divergent, in particular as
      regards financing and distribution of medicinal products. This paper explores the
      level of harmonization of pharmaceutical market in Europe, in particular in the
      light of the primary competence of the Member States in the field of healthcare
      and discusses its implications.

PMID- 22457999
TI  - Do men have rights in abortion? The Greek view.
AB  - AIM: We have examined from a legal perspective the father's role in the decision
      to abort a pregnancy in western society. Furthermore, we have taken a closer look
      into the inadequacies the Greek legal framework on this issue, from a legal and
      social point of view. METHODS: Literature in the Greek and English language.
      RESULTS: One of abortion's many victims is the father of the child. In most
      European countries and the United States of America, the law does not give any
      rights to the father on the issue of an abortion. Quite simply, men have no legal
      rights when it comes to abortion. Legally, an abortion is a private matter
      between a woman and her doctor, even if she is married. Greece was one of the
      last countries in Europe to legalize abortion after a long debate in Parliament
      and the publication of numerous declarations by women's rights organizations.
      However, despite the liberalization of abortion, which followed the ratification
      of L 1609/86, the legal framework in which abortions are carried out is not
      entirely satisfactory. One of the areas that require clarification is the role of
      father. L 1609/86 does not specify men's rights in abortion. Post-abortion
      counseling services are dealing with an increasing number of men coming forward,
      grieving their aborted children. CONCLUSION: A more careful approach is required
      and a possible review of the law on abortion may be useful. Counselling for women
      and their male partners should be offered by state organisations. Clarity of
      thinking, sympathy and understanding are prerequisites in order for a solution
      respecting the personality of both the woman and her male partner to be reached.

PMID- 22458000
TI  - Use and disclosure of health information and protection of patient privacy in
      Taiwan.
AB  - This paper examines Taiwan's current regulatory system for the use of healthcare
      information from the viewpoint of patient privacy protection. The author proposes
      a patient-centered, cooperative system centered on the "traffic light theory", as
      a solution to the potential conflict between the use of healthcare information
      and the protection of patient privacy. Taiwan, a country with a national
      healthcare insurance program and state-of-the-art electronic technology, takes a
      distinctive approach to the protection of patient privacy. On January 1st, 2004,
      the Bureau of National Health Insurance (BNHI) implemented a comprehensive
      embedded integrated circuit (IC) card, which puts the wide-ranging health
      information of its 22 million beneficiaries online to facilitate review of use
      and disclosure. It is well understood that healthcare information is of a
      personal and sensitive nature, demanding stringent privacy protection.
      Nevertheless, there is no denying the potential benefit of using personal health
      information (PHI) to achieve public good, especially in the area of cost
      containment. The comprehensive e-health system in Taiwan greatly facilitates
      copying, transmission, and use of PHI, but does the regulatory system provide
      enough safeguards for patient privacy? Because the law in Taiwan does not provide
      clear standards for the use and disclosure of healthcare information, healthcare
      providers are either too conservative or too aggressive. While most healthcare
      providers keep their oath of confidentiality, some rogue members severely abuse
      patient privacy. This paper proposes a "traffic-light system" to remedy this
      situation. Flashing yellow lights allow aggressive drivers to ignore others,
      while causing overly cautious drivers to be too hesitant. The author contends
      that clear standards should have been established for healthcare providers. Like
      car drivers, healthcare providers need red and green traffic signals. The law
      should indicate, through workable privacy regulations and guidelines, when the
      light is red or green-when to stop or to advance.

PMID- 22458001
TI  - Reflections on the syndrome of the "shaken baby".
AB  - A full appreciation of the development of current concepts concerning the "shaken
      baby syndrome" requires a systematic review of historic and more recent
      interpretations of scientific data that form the bases for diagnosis in these
      cases. This discussion relates to the dilemma in determining the cause of shaking
      injuries in this age group that are not obviously accidental or inflicted. The
      cases in question can present with similar clinical and pathological findings and
      possibly result from innocent activity. Shaking of infants and children for any
      reason should be avoided. Debates related to the circumstances and forces
      required for the development of intracranial and ophthalmic pathology as a result
      of shaking are discussed. References to the application of "markers of abuse" and
      other criteria in determining guilt or innocence in these specific situations are
      presented and evaluated.

PMID- 22458002
TI  - [What does the insurance business expect after the EuGH (court of justice)
      decision on the "Test Achats" case?].

PMID- 22458003
TI  - [Thyroid disorders].

PMID- 22458004
TI  - [Predicting long-term disability after one year for claimants with psychological
      disorders applying for vocational disability].
AB  - There is a growing amount of research on predicting the outcome of illnesses,
      return to work and early retirement. Up to now, these general findings have not
      been examined for claimants of vocational disability in the context of a private
      life insurance in Germany ("Private Berufsunfahigkeit" = BU). In this prospective
      study we tested general outcome variables for psychosomatic illnesses, when
      applying for a disability pension, to predict vocational disability after one
      year as defined by private life insurance (BU) in Germany. The results are
      consistent with the research generated in similar insurance fields, highlighting
      the relevance of the variables: Age, subjective appraisal of the vocational and
      health perspective in the following year, the amount of attempts to prevent
      disability (number of inpatient treatments) and motivational aspects like the
      extent of commitment. These variables were then used to compose a first screening
      questionnaire to predict vocational disability at an early stage of the claims
      process.

PMID- 22458005
TI  - [Health insurance companies and medical genetics, what do they want to know?
      Expert opinions concerning medical genetic services].
AB  - Based on the compilation of medical opinions delivered by a medical genetic
      expert between 2002 and 2010, solicited by private health insurance companies in
      Germany, an analysis of the main issues raised was made to identify the
      information needs of company employees with respect to human and medical
      genetics. The findings are discussed and recommendations for improvement and
      further training are suggested.

PMID- 22458006
TI  - [Comparison of two access portals of an employee assistance program at an
      insurance corporation targeted to reduce stress levels of employees].
AB  - Support programmes for stress reduction were offered independently in two
      departments (650 employees in total) of an insurance group. Both departments,
      referred to as comparison group 1 and 2 (CG1 and CG2), offered an Employee
      Assistance Programme (EAP) featuring individual consultations. The employees were
      addressed through different channels of communication, such as staff meetings,
      superiors and email. In CG1, a staff adviser additionally called on all employees
      at their workplace and showed them a brief relaxing technique in order to raise
      awareness of stress reduction. By contacting employees personally it was also
      intended to reduce the inhibition threshold for the following individual talks.
      In CG2 individual talks were done face-to-face, whereas CG1 used telephone
      counselling. By using the new access channel with an additional personal contact
      at the workplace, an above average percentage of employees in CG1 could be
      motivated to participate in the following talks. The rate of participants was
      five times as high as in CG1, with lower costs for the consultation in each case.

PMID- 22458007
TI  - [Self-discovery and self-realisation in occupational life].
AB  - Self-discovery as a maturation process begins early in infancy and is part of
      juvenile socialisation. In this early phase in life the drive of self-realisation
      may rise and continue to motivate the adolescent and further the grown-up in his
      working life. The impulse of self-realisation tends to vary along the course of
      life. While a successful carreer will strengthen the drive for self-realisation,
      lessened stimulation through continuous and dull work may result in its fading,
      as might inevitably be the case in the long-term unemployed. In occupational
      life, loss of motivation for self-realisation can induce lack of interest in
      accomplishment of the work task, thus diminishing the individual's productivity
      at the work place.

PMID- 22458008
TI  - ["Education" in an age of increasing equality--a path towards 'ochlocracy"?].
AB  - A philosophical and scientific analysis of how the concept of equality has
      developed from biological, political, sociological, social, economic and--not
      least--cultural points of view. The focus here is on the German chronic shortage
      of educational facilities continuing for decades, a cultural revolution without
      any foreseeable end. These reflections encompass a period of around two and a
      half millennia, beginning with the Ancient Greek state philosophy, reaching into
      our epoch of advanced globalisation with momentous changes in Western social
      welfare states. In consideration of a biochemical and intrinsic individuality
      based on genetic and epi-genetic factors, equal opportunities are an unlikely
      prerequisite in evolution. With regard to free education, equality can only be a
      starting point since, due to individual differences, egalitarian aims of
      education within a "group university" can never open up equally good chances to
      everybody. Because of a misunderstanding of equality, the student revolt in 1968
      brought forth an egalitarian remodeling of school and university careers
      accompanied by a leveling, among other things a "university of education for the
      masses". Instead of "educational knowledge" based on scientific nature, an
      education towards vocational knowledge and regulation of studies took place. At
      present, a socialistic reversal of the school system aimed at learning together
      in ,community schools" until the 10th grade is in progress. The unity of (pure)
      research and teaching no longer exists. The change in the system supported by a
      welfare state will have consequences in worldwide competition. The final point of
      the Cultural Revolution, following historical examples, could be the emergence of
      a degenerate form of democracy: Ochlocracy.

PMID- 22458009
TI  - [Nonsurgical therapy in symptomatic myomas].

PMID- 22458010
TI  - [Alternative medicine diagnosis and therapy of "immune deficiency"].

PMID- 22458011
TI  - [Letter to the editor on R. Hakimi: "Treatment of Struma diffusa with dried
      encapsulated swine thyroid." In: Versicherungsmedizin 2011 63(3):151-2].

PMID- 22458012
TI  - MRSA in pork production shower facilities: an intervention to reduce occupational
      exposure.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization has been
      documented in swine and swine workers. MRSA has also been found in the shower
      facilities of conventional swine farms. We previously conducted a review of the
      literature to identify measures used to reduce MRSA prevalence in athletic
      facilities. In this study, we evaluated those measures for adaptability to the
      pork production environment. A best practices protocol was developed to reduce
      MRSA levels in pork production shower facilities and implemented in two
      conventional swine production systems.

PMID- 22458013
TI  - The economic cost of farm-related fatalities in Australia.
AB  - Farm-related fatalities are a significant problem in Australian agriculture. Over
      the period 2001-2004, there were 404 fatalities that occurred as a direct
      consequence of visiting, residing, or working on a farm. This study employed a
      human capital approach to establish the economic costs of farm-related fatalities
      to the Australian economy. Modeling of direct and indirect costs associated with
      farm-related fatalities estimated that the 404 traumatic deaths over the period
      2001-2004 cost the Australian economy $650.6 million in 2008 Australian dollars
      (AUD). This equates to 2.7% of the 2008 farm gross domestic product (GDP) due to
      potentially preventable farm accidents and injuries. Farm-related deaths are a
      significant economic cost to the Australian economy. Greater resources need to be
      directed to farm health and safety interventions to increase their effectiveness
      at reducing the risk exposure of those visiting, residing, and working on
      Australian farms.

PMID- 22458014
TI  - Expected injury cost indices on Finnish farms.
AB  - Annually, more than 6000 work-related injuries occur on Finnish farms. One-fourth
      of these injuries are classified as severe, resulting in considerable economic
      losses to agricultural enterprises and the national economy. The injury rate
      among farmers is more than twice that among all employees on average. This study
      aimed to identify the risk factors that should be considered when targeting
      interventions, thus improving their cost-effectiveness. The expected injury cost
      (EIC) risk index method, which combines the probability of injuries with their
      severity and costs, was implemented. The potential risk factors included the type
      of agricultural operation, worker characteristics (gender, age), agricultural
      work tasks performed, and the geographical location of the farm enterprise. Crop
      production emerged as the type of agricultural operation with the highest risk
      index (1.12). The lowest risk index was in sheep and goat husbandry operations
      (0.35). The risk index was higher for men compared to women (1.11 vs. 0.77). The
      highest risk age group was farmers from 55 to 59 years of age (1.36). Farmers
      under 40 (0.17 to 0.89) and over 65 years old (0.70) had the lowest injury risks.
      No evidence was found that dangerous regions are concentrated in certain
      geographical parts of the country. The most common agricultural work tasks in
      which injuries occurred were the repair and maintenance of machinery and
      equipment, the transportation and relocation of animals, and milking. These
      accounted for more than one-third of all compensated work injuries in 2005. The
      identified risk factors could be considered when setting priorities in injury
      prevention and resource allocation.

PMID- 22458015
TI  - Human energy expenditure in lowland rice cultivation in Malaysia.
AB  - A study was undertaken to evaluate the human energy consumption of various field
      operations involved in lowland rice cultivation in Malaysia. Based on recorded
      average heart rates, fertilizing was found to be the most strenuous operation,
      with an average heart rate of 138 beats min(-1). There were no significant
      differences in the average heart rates of the subjects among the individual tasks
      within the first plowing, second plowing, and harvesting operations, with the
      average heart rates for these three tasks being 116, 106, and 106 beats min(-1),
      respectively. The corresponding energy expenditures were 3.90, 3.43, and 3.35
      kcal min(-1). Loading the seed into the blower tank and broadcasting the seed
      were the most critical tasks for the seed broadcasting operation, with average
      heart rates of 124 and 136 beats min(-1), respectively. The highest energy
      expenditure of 418.38 kcal ha(-1) was observed for seed broadcasting, and the
      lowest energy expenditure of 127.96 kcal ha(-1) was for second plowing. The total
      seasonal human energy expenditure for rice cultivation was estimated to be
      5810.71 kcal ha(-1), 55.7% of which was spent on pesticide spraying. Although the
      sample size in this study was relatively small, the results indicated that human
      energy expenditure per unit area (kcal ha(-1)) was positively linked to the
      average heart rate of the subjects and negatively linked to the field capacity.
      Thus, mechanization of certain tasks could decrease worker physical effort and
      fatigue and increase production.

PMID- 22458016
TI  - Identifying culturally and age appropriate farm safety curricula for Amish and
      other conservative Anabaptist youth.
AB  - In conservative Anabaptist families, especially the Amish, children play many
      vital roles; this includes participation in daily living chores as well as
      occupationally related tasks. The goal of this qualitative study was to determine
      a culturally and age appropriate farm safety curriculum useful for the children
      of Amish and other conservative Anabaptist groups. The top areas of concern
      identified were lawnmowers and string trimmers, chemicals, water, livestock,
      confined spaces, tractors, and skid loaders. Amish children were reported to
      perform farm chores at a young age. Through this study, researchers did not find
      a strong tendency for parents to assign chores based on age or gender; rather,
      these assignments were based on the child's physical development, maturity,
      interest in the task, and birth order. The findings of this study hold up the
      need for additional agricultural safety curricula targeted toward children of
      these church groups for a broad range of ages and on a variety of farm topics.

PMID- 22458017
TI  - [Significance of endothelium-derived hyperpolarizing factor].

PMID- 22458018
TI  - [Global understanding at molecular level of pain response: objective analysis of
      pain-induced distortion and pain signals].

PMID- 22458019
TI  - [Intervention by NGO of drug addicts who are in the criminal justice system in
      Japan].

PMID- 22458020
TI  - [The center of central venous catheterization (CVC) for prevention of
      complications of CVC].

PMID- 22458021
TI  - [Transition and problems of ethical guidelines for medical research in Japan].

PMID- 22458022
TI  - [Outcome research of patients with cardiac disease: comparison between Japan and
      other countries].

PMID- 22458023
TI  - [Pulmonary thromboembolism].

PMID- 22458024
TI  - [Hypoxia-inducible factor 1 constitutes a critical target for inflammatory
      regulation].

PMID- 22458025
TI  - [Brain protection in aortic surgery].

PMID- 22458026
TI  - [State of sleep science in anesthesiology].

PMID- 22458027
TI  - [Literature review: pediatric anesthesia].

PMID- 22458028
TI  - [Current topics in local anesthesia].

PMID- 22458029
TI  - [Mechanisms of action of therapeutic agents in the treatment of chronic pain in
      the spinal cord].

PMID- 22458030
TI  - [Pediatric difficult airway management].

PMID- 22458032
TI  - [What if Drucker manage a hospital?--Monitoring medical economics].

PMID- 22458031
TI  - [Fever in non-neurological critically ill patients; friends or foe?].

PMID- 22458033
TI  - [Local anesthetics inhibit NMDA-mediated glutamatergic transmission in spinal
      dorsal horn neurons].

PMID- 22458034
TI  - [Selection of pediatric endotracheal tube size by ultrasonography].

PMID- 22458035
TI  - [Gendai Kamata-Gendai and Mafutsutoron].

PMID- 22458036
TI  - [Studies on mechanism and treatment of dyspnea].

PMID- 22458037
TI  - [Study of cancer pain].

PMID- 22458040
TI  - My New Year wish list...

PMID- 22458038
TI  - [Quest for hypoxia biology as perioperative medicine].

PMID- 22458041
TI  - Question: Does sunscreen use cause vitamin D deficiency?

PMID- 22458042
TI  - Liver transplantation for hepatocellular carcinoma: indications, bridge therapy
      and adjuvant therapy.
AB  - Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide,
      and its incidence is increasing in the United and States. Liver transplantation
      has the potential to improve survival for patients with HCC. Unfortunately, not
      enough donor livers are available to meet demand for liver transplantation. The
      Milan Criteria were established to provide candidate selection guidelines for
      liver transplantation in patients with HCC. Well-established oncologic therapy
      for HCC ("bridge therapy") has the capacity to suspend tumor progression and to
      allow HCC patients to maintain active candidacy as long as necessary to obtain a
      liver. Several techniques are utilized as bridge therapies for HCC patients
      awaiting liver transplantation. Adjuvant therapies after liver transplantation
      may reduce HCC recurrence, and may be required for patients with tumors having
      high-risk biologic or histologic features. Selection criteria, adjunctive
      techniques, and outcomes in liver transplantation for HCC patients are described.

PMID- 22458043
TI  - A professional development model for medical laboratory scientists working in the
      immunohematology laboratory.
AB  - Transfusion medicine, a section of the Department of Laboratory Medicine at The
      University of Texas MD Anderson Cancer Center is committed to the education and
      advancement of its health care professionals. It is our belief that giving
      medical laboratory professionals a path for advancement leads to excellence and
      increases overall professionalism in the Immunohematology Laboratory. As a result
      of this strong commitment to excellence and professionalism, the Immunohematology
      laboratory has instituted a Professional Development Model (PDM) that aims to
      create Medical Laboratory Scientists (MLS) that are not only more knowledgeable,
      but are continually striving for excellence. In addition, these MLS are poised
      for advancement in their careers. The professional development model consists of
      four levels: Discovery, Application, Maturation, and Expert. The model was
      formulated to serve as a detailed path to the mastery of all process and methods
      in the Immunohematology Laboratory. Each level in the professional development
      model consists of tasks that optimize the laboratory workflow and allow for
      concurrent training. Completion of a level in the PDM is rewarded with financial
      incentive and further advancement in the field. The PDM for Medical Laboratory
      Scientists in the Immunohematology Laboratory fosters personal development,
      rewards growth and competency, and sets high standards for all services and
      skills provided. This model is a vital component of the Immunohematology
      Laboratory and aims to ensure the highest quality of care and standards in their
      testing. It is because of the success of this model and the robustness of its
      content that we hope other medical laboratories aim to reach the same level of
      excellence and professionalism, and adapt this model into their own environment.

PMID- 22458044
TI  - Evaluation of iron status in anemia of chronic disease among patients with HIV
      infection.
AB  - OBJECTIVE: In HIV-infected populations from developing countries, it is unclear
      what proportion of anemia is attributable to iron deficiency (ID). The objective
      of this study was to evaluate the iron status in anemia of chronic disease of
      patients with Human Immunodeficiency Virus (HIV) infection attending Federal
      Medical Centre, Makurdi. DESIGN AND SETTING: A total of 312 subjects comprising
      of 207 confirmed HIV positive patients and 105 apparently healthy subjects as
      control were evaluated for indices of anemia using SYSMEX KX 21N hematology
      analyzer machine (Kobe, Japan), CD4 count using CYFLOW SL machine (Artec,
      Germany), and total iron binding capacity and serum iron using colorimetric
      method. RESULTS: While results showed that Serum Iron, Transferrin Saturation,
      PCV, RBC, MCV, MCH, MCHC and RDWCV are within normal reference range but
      statistically different (p < 0.05) compared to the controls. Stratifying them on
      the basis of CD4 count showed that in AIDS patients the indicators are generally
      lower with Hb, PCV, MCH and RDWCV showing statistical significance (p < 0.05)
      compared with patients with CD4 > 200 cells/mm3. Serum iron (50%) and
      transferring saturation (47.9%) contributed highest to anemia prevalence
      especially in males while Hb concentration (47.2%) is the major contributor to
      anemia in females. CONCLUSION: It was concluded therefore that albeit, on
      average, the parameters of iron status did not indicate iron deficiency or iron
      overload in the HIV-status groups and AIDS patients, a large percentage of
      patients did have anemia of chronic disease with HIV-infected women afflicted
      more often. The anemia is generally normocytic hypochromic in AIDS patients.

PMID- 22458045
TI  - Improving the inter-laboratory harmonization of the international normalized
      ratio (INR): utilizing the concept of transference to estimate and/or validate
      international sensitivity index (ISI) and mean normal prothrombin time (MNPT)
      values and/or to eliminate measurement bias.
AB  - BACKGROUND: The Prothrombin Time (PT) assay is clinically the most often
      requested coagulation test, as used primarily for monitoring of Vitamin K
      antagonist therapy where results are typically expressed as an International
      Normalized Ratio (INR). The INR reflects the patient's PT adjusted for the
      specific test reagent and instrument combination used by applying two correction
      factors, namely the International Sensitivity Index (ISI) and the Mean Normal
      Prothrombin Time (MNPT), according to the formula: INR = (patient PT/MNPT)ISI.
      When the manufacturer provides an ISI, laboratories are encumbered to check or
      locally validate the assigned value. Where a manufacturer does not provide an
      ISI, the laboratory needs to define its own (local ISI) value. The MNPT typically
      has to be locally defined, based on the population being tested. The main current
      CLSI recommendation for defining ISI values comprises use of commercial reference
      ('certified') plasma calibration sets, but FDA cleared material is limited, and
      different results may arise using different products. The MNPT can be defined
      using a WHO/CLSI recommended procedure requiring 20 normal individuals or with
      some calibration sets. Overall, there is limited data to validate the performance
      of these processes in laboratory practice, and ongoing evidence from external
      quality assurance (proficiency testing) programs indicates continued failure in
      INR harmonization, suggesting that ISI and MNPT values used by laboratories (and
      presumably assessed using current recommended processes) continue to be
      inaccurate. OBJECTIVE: To assess some novel approaches to the laboratory
      estimation and/or validation of ISI and MNPT values for use in the INR
      calculation, and including the process of 'transference', normally used to assess
      the comparability of analytical systems or to transfer reference intervals
      between comparable systems. RESULTS: We have successfully adapted these
      comparative procedures, including 'transference', to permit ongoing estimation
      and/or validation of ISI and MNPT values for use in INR calculations for a range
      of instrumentation, which has led to improved harmonization of INR values
      obtained in our pathology network. These processes do not require the use of any
      normal individual plasmas or calibrator sets and greatly simplifies the INR
      process. Evidence for validation of the processes used is provided by ongoing
      satisfactory performance in external quality assurance (proficiency testing).

PMID- 22458046
TI  - Novel test method (sickle confirm) to differentiate sickle cell anemia from
      sickle cell trait for potential use in developing countries.
AB  - The objective of this study was to develop a diagnostic testing method to detect
      HbS, distinguish sickle cell homozygotes from heterozygotes, and overcome testing
      barriers encountered in laboratories in underdeveloped countries. Blood samples
      positive and negative for sickle cell were subjected to the standard hemoglobin
      solubility test followed by a variety of centrifugation and filtration
      procedures. Each procedure was evaluated for the ability to remove insoluble HbS
      from the sample. The hemoglobin types that remain (HbA, HbA2 and HbF) were
      measured spectrophotometrically or estimated visually allowing samples to be
      categorized into three genotypes (AA, AS and SS) as confirmed by hemoglobin
      electrophoresis. De-identified EDTA blood samples were obtained from Saint Louis
      University and Cardinal Glennon Children's hospitals and tested in the Department
      of Clinical Laboratory Science at Saint Louis University. The main outcome
      measures were turbidity of the solubility solution; color of the supernatant and
      the material on the surface of the solution following centrifugation; precipitate
      trapped on the filter paper; absorbance of the filtrate; and hemoglobin
      electrophoresis patterns. Centrifugation and filtration successfully separated
      HbS from HbA/A2/F allowing for the differentiation of seven sickle cell
      homozygotes from sixteen heterozygotes with a sensitivity and specificity of
      100%. This method has the potential to reliably distinguish homozygous from
      heterozygous sickle cell patients and it is fast, inexpensive, and simple. These
      characteristics make Sickle Confirm a desirable method in developing countries
      like Haiti and Africa where sickle cell anemia is prevalent and modern diagnostic
      methods like electrophoresis, HPLC and nucleic acid testing are impractical.

PMID- 22458048
TI  - Proteasome inhibitors in cancer therapy: a novel approach to a ubiquitous
      problem.
AB  - The cellular proteasome is an important molecular target in cancer therapy and
      drug resistance research. Proteasome inhibitors are effective agents against
      multiple myeloma and mantle cell lymphoma and display great potential as
      treatment for a variety of other malignancies. The proteasome is a large
      multicatalytic, proteinase complex located in the cytosol and the nucleus of
      eukaryotic cells. The ubiquitin proteasome system is responsible for the
      degradation of most intracellular proteins and therefore plays an essential
      regulatory role in critical cellular processes including cell cycle progression,
      proliferation, differentiation, angiogenesis, and apoptosis. Cancer cells are
      particularly sensitive to proteasome inhibitors, indicating the utility for
      inhibition of the ubiquitin-proteasome pathway as an approach for cancer therapy.

PMID- 22458047
TI  - Focus: advances in clinical cancer research.

PMID- 22458049
TI  - Anti-hormones: mechanism and use in treatment of breast cancer.
AB  - Breast cancer is the second-leading cause of cancer-related death in women.
      Recently, new drugs are being developed based on the molecular mechanisms of
      receptors, tumor suppressor genes, monoclonal antibodies, tumor markers and
      antihormone therapy. Anti-hormone therapy is used in the treatment of hormone
      dependent breast tumors. Among the anti-hormone therapies, a substantial amount
      of research has been focused on the development of the ideal selective estrogen
      receptor modulator to treat metastatic breast tumors and to prevent breast cancer
      in high risk women.

PMID- 22458051
TI  - [The Department of Orthopaedics and Traumatology of the University Clinics of
      Brussels, Erasme Hospital].
AB  - On the occasion of the thirty years since its inauguration, the Department of
      Orthopaedics and Traumatology of the University Hospital Erasme reviews the
      milestones of its development. Various original new techniques have been
      implemented: monitoring of implants using strain gauges, external fixation of the
      limbs, external minifixation, miniinvasive anterior approach in hip arthroplasty,
      knee ligamentoplasties, orthopaedic microsurgery and composite tissue
      allotransplantation. The care of aged patients takes place in close collaboration
      with the Department of Geriatrics. Two new clinical units have been created, the
      Unit of Hand and Peripheral Nerve Surgery, and the Centre for Sports. The
      Department has organized an efficient Bone Bank. The new day care hospital
      improves the possibilities of ambulatory surgery. The article details as well the
      activities of teaching and research of the members of the Department.

PMID- 22458050
TI  - Cancer stem cells.
AB  - The cancer stem cell (CSC) hypothesis has had a major effect on the fields of
      cancer cell biology and clinical oncology. CSCs were originally described in
      hematologic malignancies, and subsequently in a variety of solid tumors. Their
      unique biological characteristics, including self-renewal capability, stem cell
      signaling pathways, relative quiescence and resistance to standard chemotherapy
      and radiotherapy are providing researchers and clinicians with new challenges.
      One important outcome of this new perspective on tumors is the recognition that
      effective treatment approaches will need to target both the rapidly proliferating
      bulk tumor cells, and the quiescent CSCs, which contain the ability to
      reestablish the malignancy when treatment is withdrawn. The clinical laboratory
      will undoubtedly see an influx of new molecular and histopathological tests to
      augment initial diagnosis, treatment decisions, and prognostic monitoring of
      cancer patients related to identifying and quantifying these as CSCs.

PMID- 22458052
TI  - [The Orthopaedic and Traumatology Research Laboratory].
AB  - The history of the Orthopaedics and Traumatology Research Laboratory (LROT) is
      summarized during the last thirty years. The approach, initially focused on bone
      biomechanics and strength of materials, underwent a rapid diversification as
      expressed by the list of research topics: monitoring of bone healing; bone
      strains measurements for different level of activities including microgravity and
      prevention of disuse osteoporosis; biological effects of electromagnetic fields;
      evolution of the viscoelastic properties of the callus during bone healing;
      improvement of the osteoinductive properties of bone substitutes produced by the
      Tissues Bank of the University Hospital Erasme; Kashin-Beck disease; SICOT
      telediagnostic, and biomechanics of threaded implants. Those topics, event the
      most fundamental ones, have immediate significant clinical applications allowing
      a decrease of the morbidity and an acceleration of the rehabilitation of the
      patients. The results show the need of multidisciplinary collaborations
      coordinated around one autonomous laboratory, able to handle specific protocols
      requiring a dedicate environment.

PMID- 22458054
TI  - [Historical review of the treatment of fractures. Contribution of the Belgian
      surgery to the origin and development of osteosynthesis].
AB  - The word osteosynthesis was proposed by A. Lambotte in 1904. His definition,
      given in 1908, is still valid today: "Osteo-synthesis is the artificial
      contention of the bone fragments of fractures, by special devices acting directly
      on bones, exposed or not, with the aim to strongly fix them in their original
      position". The authors review the methods of contention before the invention of
      osteosynthesis and later the developments of bone fixation techniques. They
      insist in particular on the durable innovations of various pioneers including A.
      Lambotte, R. Danis, R. Hoffmann and G. Kuntscher. The School of Brussels has been
      implicated in the developments and conceptualisation of osteo-synthesis.

PMID- 22458053
TI  - [Original developments of navigation techniques in traumatology].
AB  - This article presents an original method for long objects modeling and two
      navigation applications in trauma surgery. Both concern long bone fracture
      treatment. Our modeling method requires only two x-ray views. The projection
      cones of the object are determined and their intersection is computed, providing
      an approached 30 model, which can be improved by adding a priori knowledge or
      other information. The first application concerns the control of diaphyseal
      fracture reduction treated by external fixation. Reference frames are fixed to
      the bone fragments and tracked by a 3D optical localizer, allowing the
      computation of their relative position. Approached 3D models of the fragments are
      displayed in real time according to the manipulation effected by the surgeon. The
      principal axes of the fragments, very useful for the fracture reduction, are also
      displayed. The alignment of the bone fragments is quantified by parameters
      provided in real time during the reduction. The second application concerns the
      distal locking of intra-medullary nails. A 3D model of the nail and its locking
      holes is built from two calibrated fluoroscopic views. The nail and the surgical
      tool are tracked thanks to reference frames fixed to each of them. A 3D view of
      these two elements is displayed in real time, guiding the surgeon in the
      difficult task of distal targeting. Experiments and results are presented for
      both applications. These techniques provide real 3D models to the surgeon during
      the operation, allowing precise guidance of the surgical gesture and considerable
      reduction of the irradiation to the patient and the surgical team.

PMID- 22458055
TI  - [Evolution of the biomechanical principle of osteosynthesis].
AB  - Through the technological evolution of the medical devices used for the treatment
      of bone fractures, two main concepts are in opposition: the internal rigid and
      the external elastic fixations. For forty years, the limitation due to the
      mechanical resistance of the materials have determined the various methods of
      treatment of fractures and influenced the comprehension of the physiopathology of
      bone healing. Two main figures of the Belgian orthopaedics and traumatology,
      Robert Danis and Franz Burny, had a determinant impact in this evolution.

PMID- 22458056
TI  - [Over thirty years of experience with Hoffmann external fixation in paediatric
      orthopaedics and traumatology].
AB  - The development at the Erasme University Hospital of external fixation in
      paediatric traumatology is presented following a diachronic order. External
      fixation is particularly indicated in the polytraumatized child, and/or in the
      case of an open fracture or of a fracture with associated neuro-vascular lesion.
      The indications of external fixation have been broadened to diaphyseal femoral
      fractures occurring at school age. The obtained osteosynthesis is stable and--in
      the case of an adapted mounting--elastic enough to allow the rapid constitution
      of a periosteal callus, which is mechanically favourable. The supra-condylar
      fractures of the elbow of the child may be treated by humero-ulnar distraction
      external fixation, following the principle of ligamentotaxis.

PMID- 22458057
TI  - [The Tissue Bank of the University Hospital Erasme].
AB  - The evolution of the Tissue Bank belonging to the University Hospital Erasme is
      summarized during its 13 years of experience. In parallel with this evolution,
      the important modifications of the legislation, the selection criteria and the
      bone graft processing are reported. The significant improvement of the safety of
      the allograft related to the risk of infection is also mentioned. In constant
      progression, the ongoing research within the BTE studies the osteogenic activity
      of the graft, mostly of bone demineralized matrix.

PMID- 22458058
TI  - [Nerve transfers].
AB  - Nerve transfers are recent surgical techniques where an unaffected nerve or part
      of its fascicules is transferred onto another nerve and co-apted end-to-end, or
      sometimes end-to-side, in order to "reanimate", sensitive or motor deficits. The
      technique is indicated when the proximal nerve stump has been destroyed or is of
      bad histological quality (brachial plexus root avulsion, or stump hidden in an
      extended scar), far from the target (important loss of substance), or difficult
      to access. Nerve transfers may be indicated for the microsurgical repair of
      brachial or lumbo-sacral plexus lesions, and in specific upper and lower limb
      peripheral nerve injuries : rupture of the axillary nerve in the quadrilateral
      space, irreversible lesion of the upper trunk of the brachial plexus, and in
      facial nerve surgery.

PMID- 22458059
TI  - [Treatment of severe proximal humeral fractures by proximal nailing (Telegraph).
      A prospective preliminary study].
AB  - Treatment of complex fractures of the proximal humerus is still controversial.
      This prospective study was designed to evaluate the results of open reduction and
      proximal nailing in complex fractures of the proximal humerus. Fifteen patients
      aged 39 to 83 years (average: 59 years) presenting severely displaced fractures
      of the proximal humerus were observed after open reduction and fixation by
      proximal nailing (Telegraph) combined with screwing and/or osteosuture of the
      tuberosities. The patients were evaluated at one year clinically and
      radiologically. The Constant score, DASH score and Simple Shoulder Test were
      calculated. Complementarily, patients were submitted to an isokinetic test. At
      one year follow-up, the average range of motion was 85 degrees (40 degrees-170
      degrees) for elevation, 82 degrees (40 degrees-170 degrees) for abduction, L3 for
      internal rotation and 34 degrees (10-60 degrees) for external rotation. The
      average visual analog score was 3 points (0-8 points). The Constant score varied
      from 17 to 92 points (average: 48 points). Isokinetic evaluation showed mostly a
      strength deficit in abduction even for patients presenting an excellent result.
      Functional results were related to the quality of the surgical reduction but also
      to patients' collaboration. Various treatment methods for complex fracture of the
      proximal humerus are reported in the literature. When a nearly anatomical
      reduction is achieved, the here-described method of open reduction and proximal
      nailing permits to obtain good functional results in most patients. This option
      should be considered for young patients and even in the elderly where results are
      comparable to that obtained with hemiarthroplasty in the same condition.

PMID- 22458060
TI  - [The first Belgian hand transplantation case. Nine years follow-up].
AB  - The authors report the clinical result at 9 years followup of a unilateral hand
      transplantation performed on the dominant side after traumatic forearm
      amputation. The patient is back to work and sporting activities. The allograft
      has been fully incorporated into his self-image. The satisfaction index is 10/10,
      the DASH 5/100, and the 400-points score 68.1 %. The Lanzetta HTSS score is 91
      (excellent). Good function of extrinsic and intrinsic muscles is observed. The
      grasping strength is markedly decreased (7.4 % as compared to the normal non
      dominant side). The patient has experienced several rejection episodes,
      controlled by the immunosuppressant drugs.

PMID- 22458061
TI  - [External fixation at the wrist and hand].
AB  - Distraction radio-metacarpal external fixation is an excellent technique for the
      osteosynthesis of distal radius fractures, in particular of comminuted articular
      fractures. The alternative is the locked palmar plate, a more demanding
      technique. The published literature does not allow concluding if one method is
      better than the other. The other main possible indications of external fixation
      at the wrist are comminuted fractures of the base of the thumb metacarpal, distal
      radius osteotomies, and wrist arthrodeses. At the hand, external minifixation is
      an excellent technique of osteosynthesis. Stable bone fixation is obtained,
      allowing early active mobilization of the fingers. The technique is especially
      indicated to treat open lesions or to perform lengthening, but we use also
      external minifixation to treat closed fractures, to perform arthrodesis or to
      cure non-unions, and to maintain the length of the thumb after trapeziectomy for
      osteoarthrosis.

PMID- 22458062
TI  - [Total hip arthroplasty by mini-approach: review of literature and experience of
      direct anterior approach on orthopaedic table].
AB  - In addition to the choice of the surgical approach, the respective place of the
      mini-incisions and mini-invasive surgery for total hip arthroplasty (THA) remains
      a controversial topic. The purpose of this study was to specify the advantages
      and disadvantages of these different approaches by a systematic review of the
      orthopedic literature and by our experience of the first 100 THA implanted by
      mini-invasive direct anterior approach (DAA) on orthopedic table. Selecting 15
      orthopedic journals, we found 252 articles among which 65 are particularly
      relevant; 25 correspond to randomized studies. Mini-invasive approaches permit to
      obtain results at least equivalent to standard approaches with regard to
      operative time, general complications and adequate component positioning.
      Contrarily to posterior approach, DAA is associated to a low dislocation rate,
      even in so-called "at risks patients". Recent randomized studies highlight an
      earlier functional recovery in patients treated by mini-invasive approaches and
      particularly by DAA. This advantage seems to persist only the first six weeks but
      it could be interesting to patients avid to resume quickly their activities.
      Nevertheless, further studies are mandatory to confirm the observed results and
      to specify the place of the mini-invasive approaches with regard to early
      recovery as long-term results.

PMID- 22458063
TI  - [Management of the meniscal lesion].
AB  - About 1,5 million arthroscopies are each year performed in the world, 50 % for
      meniscal affections. The menisci participate in the femoro-tibial load
      transmission and in the joint shock absorption; they contribute to the knee
      stability and play a role in the joint lubrication. The menisci are therefore
      important structures, and, in the case of a lesion, surgical abstention or repair
      should be favoured. When a meniscectomy has to be performed, it should be
      economical, preserving the meniscal wall. Meniscectomy is contra-indicated in the
      child and in the case of knee osteoarthrosis. Meniscal healing is compromised if
      the knee is unstable. If after total meniscectomy a patient presents symptomatic
      early osteoarthrosis, without marked loss of alignment, meniscal allografting is
      a therapeutic option, especially at the lateral compartment.

PMID- 22458064
TI  - [Reconstruction of the knee anterior cruciate ligament: single or double
      bundle?].
AB  - Anatomical and biomechanical studies have shown that the anterior cruciate
      ligament (ACL) consists of two distinct bundles, the anteromedial (AM) and
      posterolateral. Each bundle has its specific role during the motion of the knee.
      ACL reconstruction techniques have focused on the restauration of the
      anteroposterior stability by substituting the more isometric AM bundle. Although
      these ligamentoplasties provide overall good results, in the last ten years
      double-bundle ACL reconstruction techniques have been developed, to better
      replicate the ligament anatomy. Despite the growing number of published studies,
      including randomized controlled trials comparing single bundle and double bundle
      reconstructions, there is still a lack of evidence of any superiority of the
      double-bundle technique. Furthermore, many series are criticized for their poor
      assessement of rotational stability, using most of the time subjective pivot
      shift clinical testing. Among the methods available to measure tibial rotation, 3
      D optoelectronic evaluation is an attractive tool and has been used in some
      studies reporting rotational mesurements after ACL single-bundle reconstruction.
      Our Department of Orthopaedics and Traumatology has been using double-bundle
      techniques for a few years. We conducted a preliminary prospective randomized
      study, in order to compare single and double-bundle techniques by clinical and
      optoelectronic evaluations.

PMID- 22458065
TI  - Sneak preview.
AB  - Hospitals were grateful for the advance look they got of the value-based
      purchasing program, but the convoluted calculations have some nonplused.
      "Competition is so high that even if you are above the 90th percentile, you could
      still have a very poor score and leave money on the table," says Tami Lewis, of
      Robinson Memorial Hospital, Ravenna, Ohio. "How do you convey a message like that
      to employees?"

PMID- 22458066
TI  - Drug-diversion turf war: will Cardinal ruling reinvent roles, DEA strategy?

PMID- 22458067
TI  - Battle not over: FTC wants Supreme Court to review Palmyra case.

PMID- 22458068
TI  - Certification could expand: proposed rule suggests testing long-term-care EHRs.

PMID- 22458069
TI  - CEO turnover holds: but it's not likely to stay that way: ACHE president.

PMID- 22458070
TI  - New deals, new friction: competition heads up for payers, providers.

PMID- 22458071
TI  - Data satisfaction: home health reps say there are no OASIS issues.

PMID- 22458072
TI  - Shaky outlook: Roman Catholic healthcare being dragged down by inflexibility.

PMID- 22458073
TI  - New standard of care: health IT not only benefits patients, but will offer
      healthy return on investment.

PMID- 22458074
TI  - For-profits rising.

PMID- 22458075
TI  - The direct route: more hospitals turning to banks for direct-placement borrowing.

PMID- 22458076
TI  - Nurses face new "customer rating".

PMID- 22458077
TI  - "NMC review must hear nurses' concerns about their regulator".

PMID- 22458078
TI  - "Emotional support for nurses is as vital as doughnuts for the police".

PMID- 22458079
TI  - "Systems such as red trays erode essential nursing skills".

PMID- 22458080
TI  - Using OSCE for mandatory training.
AB  - Mandatory training for nursing staff is vital to ensure the safety of patients,
      staff and visitors. This article discusses using objective structured clinical
      examination to structure this training.

PMID- 22458081
TI  - Education to increase sexual health screening.
AB  - Rates of sexually transmitted infections among young people aged 16-24 years have
      soared in recent years. Opportunistic screening for chlamydia and other STIs
      identifies asymptomatic infection but encouraging this group to take up screening
      remains a major challenge. National guidance recommends structured one-to-one
      discussions with young people to achieve behavioural change. Although
      opportunities for this are rare, the sexual health outreach team in Nottingham
      has developed an interactive educational module for use with groups of young
      people and combined it with sexual health screening, with initial positive
      results.

PMID- 22458082
TI  - Using ARC to avoid unplanned pregnancy.
AB  - Long-acting reversible contraception (LARC) extends choice for women about when
      and how they use contraception. This article outlines the advantages and
      disactdisadvantages of different LARC methods.

PMID- 22458084
TI  - 60 seconds with Tara Bartley.

PMID- 22458083
TI  - Osteoarthritis 2: pain management and treatment strategies.
AB  - Osteoarthritis (OA) is a painful, progressive joint disorder. This article
      discusses pharmacological management of OA, such as non-steroidal anti
      inflammatory drugs and opioids, and non-pharmacological management, including
      weight reduction, acupuncture and joint replacement surgery. The third part, to
      be published online, will cover the physical, psychological and social impact of
      OA.

PMID- 22458085
TI  - Starting clinics from scratch.

PMID- 22458086
TI  - How to get a new idea to work.

PMID- 22458087
TI  - Filling the gap in Afghanistan.

PMID- 22458088
TI  - Moving the foundation forward. Interview by Michi Trota.

PMID- 22458089
TI  - Supporting our community.

PMID- 22458090
TI  - Military community involvement in Germany.

PMID- 22458091
TI  - Providing oral care for those in need.

PMID- 22458092
TI  - Best practices for aging adults in private dental practice.

PMID- 22458093
TI  - A case of relapsed disseminated cutaneous MALT lymphoma.
AB  - A 50-year-old African American woman, with a history of hepatitis C and prior
      Mucosal Associated Lymphoid Tissue (MALT) lymphoma of the hard palate, presented
      to the Emergency Department with a chief complaint of fatigue and "bumps on my
      skin." Examination revealed multiple subcutaneous nodules on her extremities,
      torso, and back including a 10 by 6 cm mass on her left anterior thigh. Cytology
      from one of these subcutaneous nodules was consistent with extranodal marginal
      zone B cell lymphoma. This is a unique case in that it represents relapse and
      dissemination of MALT lymphoma to a completely new site following a complete
      remission status post radiation and chemotherapy.

PMID- 22458094
TI  - Walking the walk to better health.

PMID- 22458095
TI  - Different direction, opportunities.

PMID- 22458096
TI  - ANA survey: improved work environment, more can be done.

PMID- 22458097
TI  - Action urged to fight health care worker fatigue.

PMID- 22458098
TI  - MONA nurse researches lymphedema.

PMID- 22458099
TI  - Clinical privileges: opening doors for APRNs.

PMID- 22458100
TI  - Surge in younger nurses spurs RN growth.

PMID- 22458101
TI  - Repaving tobacco road.

PMID- 22458102
TI  - Steps that lead to success.

PMID- 22458103
TI  - Marketing on a shoestring.

PMID- 22458104
TI  - We are family.

PMID- 22458105
TI  - In with the new.

PMID- 22458106
TI  - Build a confident employee culture.

PMID- 22458107
TI  - The supercommittee failed; health care must not.

PMID- 22458108
TI  - Change of status: the conversion from nonprofit to for-profit status requires
      extensive due diligence from the board.
AB  - Trustees must demonstrate due diligence in a for-profit conversion.

PMID- 22458109
TI  - Telemedicine today: new gadgets and lower costs make this mode of care a
      strategic advantage for rural and urban hospitals.
AB  - Across the country or across town, connecting patients to clinicians is easier
      and cheaper than ever.

PMID- 22458110
TI  - Action plans for better care: hospitals are using a variety of strategies to
      improve the patient experience.
AB  - With an eye on HCAHPS, hospitals are using a variety of strategies to improve the
      patient experience.

PMID- 22458111
TI  - Under the microscope: public boards face unique governance challenges, yet find
      ways to thrive.
AB  - Boards of publicly funded hospitals learn how to navigate unique governance
      challenges.

PMID- 22458112
TI  - The next great explorers: only the bravest, most skilled leaders will discover
      health care's new world.
AB  - As with health care, the CEO role is undergoing a transformation. New skill sets
      will be needed.

PMID- 22458113
TI  - Environmental sustainability programs for hospitals.
AB  - The board and CEO must lead environmental sustainability efforts.

PMID- 22458114
TI  - Brief tenure, lasting benefits: an interim CEO can stabilize an organization and
      provide the foundation for long-term success.
AB  - Interim leaders can set the stage for long-term success.

PMID- 22458115
TI  - How to build an ACO: Medicare's shared savings program includes specific
      structural and governance requirements.
AB  - Is your organization prepared to build a shared savings ACO?

PMID- 22458116
TI  - Lymphatic architecture of the human gingival interdental papilla.
AB  - Many studies have investigated the lymphatic architecture of head and neck using
      experimental animals, confirming the existence of lymphatic networks beneath the
      epithelium in gingival tissue. In this study, we investigated the use of these
      lymphatics as a drug delivery route by studying the architecture of lymphatic
      vessels in human interdental papilla. Serial cryosections were cut using the film
      transfer method. To identify lymphatics, the sections were stained using enzyme
      histochemical and immunohistochemical techniques and three-dimensional images of
      lymphatics were reconstructed using 3D visualization software. Capillary
      lymphatic networks were observed in the lamina propria beneath the epithelium in
      human interdental papilla, and they joined with lymphatic networks beneath the
      epithelium in free gingiva. The networks consisted of a single layer of large
      irregular, hexagonal meshes and precollecting lymphatic vessels heading toward
      collecting lymphatic vessels that exited on the periosteum of the alveolar crest.
      These findings suggest that lymphatic flow from the interdental papilla drains
      into collecting lymphatic vessels running buccolingually on the alveolar crest of
      the interdental papilla. This may be an important anatomical feature during
      inflammation throughout the oral cavity in that the drainage function is
      maintained by part of lymphatic flow that is not impaired during the healing
      process.

PMID- 22458117
TI  - Classification of lymphoscintigraphy and relevance to surgical indication for
      lymphaticovenous anastomosis in upper limb lymphedema.
AB  - Upper limb lymphedema that develops after breast cancer surgery causes physical
      discomfort and psychological distress, and it can require both conservative and
      surgical treatment. Lymphaticovenous anastomosis has been reported to be an
      effective treatment; however the disease severity criteria that define
      indications for this treatment remain unclear. Here, we examined
      lymphoscintigraphic findings in 78 patients with secondary upper limb lymphedema
      and classified them into 5 major types (Type I-V) and 3 subtypes (Subtype E, L,
      and 0). Results revealed that this classification is related to the clinical
      stage scale of the International Society of Lymphology. Based on intraoperative
      examination findings in 20 of the 78 patients, lymphatic pressure is likely to be
      further elevated in Type II-V cases which are characterized by the presence of
      dermal back flow. Therefore, lymphaticovenous anastomosis should be considered as
      a treatment option for lymphedema in Type II-V cases. Furthermore, there are only
      limited lymph vessel sites usable for lymphaticovenous anastomosis in more severe
      lymphedema types [Types IV and Type V (which is characterized by dermal backflow
      only in the hand)]. The findings in Type IV-V cases suggest that therapeutic
      strategies for severe upper limb lymphedema need further consideration.

PMID- 22458118
TI  - Changes in tissue water and indentation resistance of lymphedematous limbs
      accompanying low level laser therapy (LLLT) of fibrotic skin.
AB  - Our goal was to determine effects of low-level-laser-therapy (LLLT) on skin water
      and tissue indentation resistance (TIR) in patients with arm (N = 38) or leg (N =
      38) lymphedema. Skin water was determined from tissue dielectric constant (TDC)
      measurements and TIR determined from measurements of force resulting from tissue
      indentations of 3-4 mm. A limb-location with fibrosis was identified by palpation
      and treated with an LLLT device for one minute at each of five points within a 3
      cm2 area. TDC and TIR at these sites and corresponding sites on the contralateral
      limb were measured prior to LLLT (pre-LLLT), immediately after LLLT (post-LLLT)
      and after a manual lymphatic drainage (MLD) session (post-MLD). Results, from
      arms and legs, showed that post-LLLT values of TIR and TDC were significantly
      less than pre-LLLT. TIR values remained significantly reduced at post-MLD whereas
      TDC values were not significantly different from pre-LLLT values. On follow-up
      visit, 17 previously LLLT treated legs were sham treated with an inactive LLLT
      unit and measurements replicated. A TIR and TDC change-pattern similar to that
      obtained with the active LLLT was obtained, but sham-related reductions in TIR
      and TDC immediately post sham-treatment were significantly less than achieved
      with the prior active LLLT treatment.

PMID- 22458119
TI  - Lymphedema treatment decreases pain intensity in lipedema.
AB  - Lipedema is a disproportional obesity featuring light pressure-induced or
      spontaneous pain. On the basis of our clinical observations, lymphedema therapy,
      as practiced in our clinic, reduces the perception of pain beyond leg volume
      reduction. We therefore aimed to measure pain intensity prior and subsequent to
      treatment. 38 women with lipedema were enrolled in the study with 19 patients
      undergoing treatment and 19 serving as the control group using exclusively
      moisturizers. Treatment consisted of once daily manual lymph drainage (MLD),
      intermittent pneumatic compression (IPC), and multilayered short-stretch
      bandaging performed throughout a 5-day-course. Pain was evaluated with a 10-item
      questionnaire, a pain rating scale (PRS), and the Wong-Baker Faces scale.
      Treatment resulted in a significant reduction of pain with a decrease in mean
      scores of all three measures. In the control group, only PRS showed significant
      decrease. Our study results indicate that this treatment regimen not only reduces
      leg volume and capillary fragility, but also improves pain intensity in patients
      with lipedema.

PMID- 22458120
TI  - Severe lymphedema caused by repeated self-injury.
AB  - Lymphedema is divided into primary and secondary forms. Primary lymphedema often
      develops in young people and may be caused by lymphvascular aplasia, hypoplasia,
      and hyperplasia. The most frequent cause of secondary lymphedema after lymphatic
      filariasis is regional lymph node dissection for treatment of a malignant tumor,
      and this complication occurs most frequently in middle aged or older patients.
      Here, we describe a relatively young patient (27 years old) in whom collecting
      lymph vessels in the upper limb were disrupted by repeated self-injury, with
      resultant lymphedema. There have been very few reports on lymphedema caused by
      self-induced trauma. This case report illustrates that secondary lymphedema
      should also be considered and evaluated appropriately when diagnosed in a
      relatively young patient without a history of cancer or infection.

PMID- 22458121
TI  - [Strange wounds and skin changes--consider leishmaniasis].

PMID- 22458122
TI  - [Cutaneous leishmaniasis is a neglected tropical skin infection. Swedish military
      infected in Afghanistan].

PMID- 22458123
TI  - [Female breast deviations].

PMID- 22458124
TI  - [High survival rate among newborns with congenital diaphragmatic hernia. 20-year
      follow up of patients treated in Stockholm].

PMID- 22458125
TI  - [When research ethics goes astray].

PMID- 22458126
TI  - [Snuff use cessation with varenicline: Swedish snuff - again].

PMID- 22458127
TI  - [The registration of Swedish fibrillation surgery fails. What about the
      evidence?].

PMID- 22458128
TI  - [Screening for lung cancer can save lives, according to US study. Too early for
      mass screening--but refer smokers to CT on broad indications].

PMID- 22458130
TI  - [Lactose intolerance in children is an overdiagnosed condition. Risk of missing
      intestinal diseases such as IBD and celiac disease].

PMID- 22458129
TI  - [Surgical treatment of atrial fibrillation in connection with cardiac surgery.
      Consensus report from Swedish cardiac surgeons responsible for arrhythmia].

PMID- 22458131
TI  - [Moderate intake of alcohol did not cause hepatic steatosis. However significant
      reduction of LDL cholesterol was observed in a prospective study].

PMID- 22458132
TI  - [Psychosomatic pain diagnosis should be based on established criteria. Can
      provide opportunities for improved care].

PMID- 22458133
TI  - [Two cases of pellagra. The 4D disease--forgotten but fatal].

PMID- 22458134
TI  - [Do women with premenstrual symptoms benefit from the condition being
      ideologized?].

PMID- 22458135
TI  - [Change in the Driver's Licence Act from February 1 applies to all physicians:
      Reporting is now mandatory, not optional].

PMID- 22458136
TI  - [Simple cure for the corn eaters mysterious soot].

PMID- 22458137
TI  - Not all about bones: the non classical role of vitamin D in public health.

PMID- 22458138
TI  - Sun exposure and vitamin D.

PMID- 22458139
TI  - Intersections of context and HIV/AIDS in sub-Saharan Africa: what can we learn
      from feminist theory?

PMID- 22458140
TI  - A brief introduction to ... public health and midwifery.

PMID- 22458141
TI  - Championing health in your community.

PMID- 22458142
TI  - Health promotion awards 2011: recognising today's health promotion.

PMID- 22458143
TI  - Debate about the purposes of education.

PMID- 22458144
TI  - How to avoid 'dad dancing': a peer-led approach to the delivery of health
      education in secondary schools.

PMID- 22458145
TI  - Health education in schools: strengths and weaknesses in relation to long-term
      behaviour development.

PMID- 22458146
TI  - ESOL for health: helping those with limited English language skills to use the
      NHS.

PMID- 22458147
TI  - Health literacy and public health: a framework for developing skills and
      empowering citizens.

PMID- 22458148
TI  - Understanding and health literacy.

PMID- 22458149
TI  - 'No decision about me, without me': a place for social marketing within the new
      public health architecture?
AB  - July 2011 marked the 40th anniversary of social marketing. However, while the
      previous Labour administration dedicated sustained resources and support to
      developing the field of social marketing, this was followed by a time of
      uncertainty during the Coalition Government's ascent to power. This paper
      explores the potential future position of social marketing within David Cameron's
      evolving public health landscape, outlining areas of synergy between social
      marketing's key features, and the coalition's emergent public health
      architecture. The paper concludes with an exploration of the development
      opportunities nascent within social marketing, suggesting that support for the
      new commissioners (GP and local authority), and an enhanced emphasis on
      evaluation of financial and social outcomes, will be required if the evidence
      base for strong practice is to continue to grow and evolve.

PMID- 22458150
TI  - Health literacy in Ireland: reading between the lines.
AB  - Health literacy may be defined as the degree to which individuals have the
      capacity to obtain, process, and understand basic health information and services
      needed to make appropriate health decisions. While health literacy has become a
      vibrant area of international research, Ireland has lagged behind and to date few
      data exist. This article summarises the research that has been carried out in
      Ireland, highlighting key findings and recommendations. With several new
      initiatives in place such as the Crystal Clear health literacy Awards, it is
      expected that Ireland will lag behind in this field no longer. Inadequate health
      literacy is at epidemic levels in Ireland and is fast becoming recognised as a
      national issue. Simplification of the healthcare system, in its entirety is
      required but the much needed financial investment will only be made after
      original research, demonstrating successful interventions has been conducted.
      With a trend worldwide towards personalized medicine, this theme should be
      extended to include tailor-made personalized health care information. An
      investment in health literacy will ultimately increase a patient's self-esteem,
      compliance, capacity to self-manage and most importantly patient outcomes and
      safety.

PMID- 22458151
TI  - Health literacy and the clozapine patient.
AB  - AIMS: To estimate the prevalence of limited health literacy in patients receiving
      clozapine for schizophrenia. To develop and produce a pharmacist-designed
      clozapine patient information leaflet (PIL) which has a higher readability score
      than the company-produced PIL. STUDY DESIGN: This was a cross sectional
      prevalence study. METHODS: Ethical approval for the study was granted by the
      local ethics committee. Patients, over 18 years, attending the Clozapine Clinic
      of a Cork urban teaching hospital, were asked to participate in the study.
      Demographics such as gender, age, employment and smoking status, were gathered
      from all participants. The total daily clozapine dose, duration of clozapine
      treatment, and information regarding the clozapine DVD was also noted. The Rapid
      Estimate of Adult Literacy in Medicine (REALM) health literacy (HL) screening
      tool was then administered to each patient. A user-friendly PIL on clozapine was
      designed by the pharmacist, which was assessed for readability and compared to
      the company-produced PIL using the FRES and FKGL. Data were analysed using SPSS
      Version 15. RESULTS: Forty patients (65% male, 95% unemployed and 70% smokers) of
      average age 38.0 years (+/- 11.2) completed the REALM. The average score was 60.6
      (+/- 8.7). Twenty-nine patients (72.5%) were found to have "adequate" health
      literacy. The remaining eleven patients were found to have either "marginal" or
      "low" health literacy. The pharmacist-designed PIL would have been readable by
      95% of the study population, in contrast to 72.5% with the company-designed PIL.
      CONCLUSIONS: More than a quarter of the population were found to have marginal or
      low health literacy. Patient information should be matched to the health literacy
      level of the target population.

PMID- 22458152
TI  - Charting a health literacy journey--overview and outcomes from a stakeholder
      workshop.
AB  - Through a combination of Personal, social, health and economic education (PSHE),
      Science, Healthy Schools and a range of other initiatives, we are increasingly
      preparing our children to understand key topics in health education. However, to
      what extent are we equipping them with a picture of a healthy, happy future and
      giving them the tools to access this? In June, The Royal Society for Public
      Health (RSPH) hosted a workshop entitled "Charting a Health Literacy Journey" to
      examine this. The workshop brought together a broad group of over 20 stakeholders
      from the health and education sectors. The aims of the day were to address the
      following six questions: What is health literacy? What does health literacy look
      like in action? What are the benefits of health literacy? How is health literacy
      reflected on the ground at present? How does health literacy fit with the current
      policy context? What are the options going forward? This report summarises the
      key findings of the workshop.

PMID- 22458153
TI  - FIPPA and Ontario hospitals: issues for shared service entities.

PMID- 22458154
TI  - Federal court invalidates Sanofi's Plavix patent for alleged insufficiency and
      obviousness.

PMID- 22458155
TI  - Employee dismissed for incomplete medical disclosure prior to hiring.

PMID- 22458156
TI  - [At 16 degrees C unconscious in the woods. The damage cold causes].

PMID- 22458157
TI  - [French health care system in crisis. United Europe - also in physician
      frustration].

PMID- 22458158
TI  - [Professional politics. Reducing bureaucracy involves drilling through thick
      planks].

PMID- 22458159
TI  - [Treating wrinkles in the man. "Men want to be extremely smooth" (interview by
      Dr. Beate Schumacher)].

PMID- 22458160
TI  - [From earache to hearing loss. Otology for the family physician].

PMID- 22458161
TI  - [Burnout. What to do when "simply nothing works out"?].

PMID- 22458162
TI  - [Incidental finding in an alcoholic patient. Aortic dissection - but the patient
      doesn't notice anything].

PMID- 22458163
TI  - [Anemia in the elderly patient. Is it a myelodysplastic syndrome?].

PMID- 22458165
TI  - [Physical activity in aging. Proper training protects seniors from accidental
      falls].

PMID- 22458164
TI  - [Important therapy goal in diabetics. Intercept hypoglycemias!].

PMID- 22458166
TI  - [Rheumatoid arthritis plus osteoporosis. How much corticoid will this patient
      still tolerate?].

PMID- 22458167
TI  - [Patients with unexplained symptoms in general practice].

PMID- 22458168
TI  - [Depression in general practice].

PMID- 22458169
TI  - [Never say: "it's nothing. Improving care for patients with non-specific,
      functional and somatoform bodily complaints].

PMID- 22458170
TI  - [Heat inactivated lactobacilli in diarrhea. Rapid management of diarrheal
      diseases of various origins].

PMID- 22458171
TI  - [Acute exacerbation of chronic obstructive pulmonary disease].

PMID- 22458172
TI  - [Acute lower back pain].

PMID- 22458173
TI  - [Dislocation of the total hip arthroplasty].

PMID- 22458174
TI  - [Mandibula advancement devices in therapy of snoring and apneas].

PMID- 22458175
TI  - [Laparoscopic methods in visceral surgery--is minimal access surgery better than
      open surgery?].

PMID- 22458176
TI  - [5 plant combination with antiviral effect. With bioflavonoids against
      rhinosinusitis viruses].

PMID- 22458177
TI  - [Blood pressure control in patients with diabetes mellitus. Focus on postprandial
      blood glucose values and cardiovascular risk].

PMID- 22458178
TI  - [Chronic backache. Rational therapy of muscle-induced pain].

PMID- 22458179
TI  - Heterotopic implantation of autologous bone marrow in rock pigeons (Columba
      livia): possible applications in avian bone grafting.
AB  - Autologous bone marrow, alone or as a composite marrow graft, has received much
      attention in various species. To assess the potential osteogenicity of
      autologous, extramedullary bone marrow implants in an avian model, 24 adult
      pigeons (Columba livia) were given intramuscular implantations of autologous
      marrow aspirated from the medial tibiotarsus. Birds were euthanatized at 1, 4, 6,
      8, 10, and 12 weeks after surgery to evaluate whether ectopic bone had formed at
      the implant sites. Primary evaluations by in situ radiography and postmortem
      histologic examinations showed no evidence of bone formation. Further evaluation
      with histologic scores and histomorphometry revealed a significantly increased
      rate of angiogenesis at the implant sites by the sixth and tenth week
      postimplantation (P < .05). No significant differences between the treatment and
      control sites were present at any other endpoints. Results of this study show
      that, although autologous bone marrow lacks heterotopic osteogenic potentials in
      this avian model, it could still function as a useful adjunct to routine bone
      grafting techniques because of its unique capabilities to promote early
      angiogenesis.

PMID- 22458180
TI  - Radiographic measurement of internal organs in Spix's macaws (Cyanopsitta
      spixii).
AB  - Radiology is an important diagnostic instrument in avian medicine, but standard
      measurement ranges for the objective evaluation of radiographs of birds are rare.
      To establish radiographic reference ranges for the critically endangered Spix's
      macaw (Cyanopsitta spixii), we measured radiographic silhouettes of the heart,
      liver, kidneys, spleen, proventriculus, and keel of the sternum on 29 radiographs
      taken under standardized conditions in adult and juvenile, clinically healthy
      birds. Ratios were determined for the proventricular diameter-to-keel height, the
      width of the heart to the width of the thorax, and for the "hourglass shape"
      (ratio of the width of the heart to the width of the liver). No significant
      differences were found between the sexes among the adult birds. Compared with
      adult birds, juvenile females had a significantly larger heart width (19.8 +/-
      1.4 mm versus 21.2 +/- 0.7 mm), ratio of the heart width to the thorax width
      (0.86 +/- 0.08 versus 0.94 +/- 0.09), and horizontal width of the spleen (7.7 +/-
      0.6 mm versus 8.5 +/- 0.4 mm). Results of radiographic measurements in the Spix's
      macaws were comparable to those published from other psittacine species. These
      reference ranges will facilitate a more objective radiographic evaluation of
      captive Spix's macaws.

PMID- 22458181
TI  - Pharmacokinetics of clindamycin administered orally to pigeons.
AB  - To determine the plasma concentration of clindamycin in pigeons after oral
      administration, 12 rock pigeons (Columba livia) were used in a 2-phase study. In
      the first phase, 8 pigeons received clindamycin by gavage at 100 mg/kg as a
      single dose. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, and 6
      hours, and the plasma was separated, frozen, and subsequently analyzed by liquid
      chromatography-mass spectrometry for clindamycin and its active metabolites, N
      demethylclindamycin (NCLD) and clindamycin sulfoxide. Clindamycin was rapidly
      absorbed with plasma concentrations peaking at 0.5 hours at 1.43 microg/mL. The
      terminal half-life (t(1/2)) was 1.25 hours, and the mean residence time was 2.49
      hours. N-demethylclindamycin was detected in 7 of 8 birds (88%), whereas
      clindamycin sulfoxide was not found in any samples. In phase 2, clindamycin was
      administered to 3 birds by gavage at 100 mg/ kg q6h for 5 doses. Mean peak plasma
      concentrations were 2.46 and 0.64 microg/mL, with trough concentrations of 0.11
      and 0.44 microg/mL for clindamycin and NCLD, respectively. No adverse effects
      were observed in any birds. Based on an additive antimicrobial effect of NCLD
      with clindamycin, an oral dosage of 100 mg/kg q6h in pigeons should reach
      effective plasma concentrations against common susceptible pathogens. If dose
      proportionality exists, lower doses and longer intervals likely produce
      subtherapeutic concentrations to treat systemic infections. How well birds would
      tolerate an extended oral dose regimen, how frequently birds fail to produce the
      active metabolite critical for an additive effect, and the application of these
      results to other avian species require further study.

PMID- 22458182
TI  - Intermittent claudication-like syndrome secondary to atherosclerosis in a yellow
      naped Amazon parrot (Amazona ochrocephala auropalliata).
AB  - A 25-year-old yellow-naped Amazon parrot (Amazona ochrocephala auropalliata) was
      presented for nasal discharge and sneezing. Physical examination revealed poor
      feather quality, a mild serous nasal discharge, and a mass on the dorsal surface
      of the oral cavity. Cytologic examination of a mass aspirate as well as results
      of a choanal culture revealed squamous metaplasia of the salivary glands and
      bacterial rhinitis, respectively. Following resolution of the presenting
      conditions, the patient was presented for hind limb weakness and ataxia. The
      clinical signs were transient and generally resolved with rest but could be
      reproduced after stressful episodes, such as restraint for procedures or
      treatment. Test results from a complete blood count, biochemistry profile, whole
      body radiographs, needle electromyography of the leg muscles, and an edrophonium
      challenge test were within reference limits. Based on the clinical signs and
      results of the diagnostic workup, the presumptive diagnosis was intermittent
      claudication, a condition caused by peripheral vascular disease and defined as
      intermittent weakness and pain in the legs induced by exercise and relieved by
      rest. Shortly after initiation of treatment with isoxsuprine, the bird died.
      Postmortem examination and histopathology revealed severe atherosclerotic lesions
      throughout the vascular system with stenotic lesions present in the abdominal
      aorta and femoral arteries. Electron microscopic examination of the great
      arteries was also performed and helped to further characterize the nature of the
      lesions. This case is the first report, to our knowledge, of an intermittent
      claudication-like syndrome associated with peripheral atherosclerosis in a
      psittacine bird. In addition, the distribution and some of the macroscopic and
      histopathologic features of the lesions differ from previous descriptions of
      atherosclerosis in psittacine birds.

PMID- 22458183
TI  - Cloacal fibrosarcoma in a canary (Serinus canaria).
AB  - A 1-year-old, male canary (Serinus canaria) with a history of an enlarged abdomen
      of several days duration died acutely and was submitted for necropsy. Results
      revealed a yellow to tan hard mass, 2 cm in diameter, adherent to the cloacal
      wall. Histologically, the mass was composed of interlacing bundles of pleomorphic
      spindle cells with numerous and bizarre mitotic figures. Neoplastic cells were
      positive for vimentin and negative for desmin and actin and showed
      ultrastructural features (dilated stacks of rough endoplasmic reticulum,
      intermediate filaments, rare collagen secretion granules, lack of external
      lamina) typical of fibroblasts. Based on these results, the diagnosis was cloacal
      fibrosarcoma, previously not reported in canaries.

PMID- 22458184
TI  - Suspected osteoma in an eclectus parrot (Eclectus roratus roratus).
AB  - A 7-month-old, male eclectus parrot (Eclectus roratus roratus) was presented with
      a slow-growing mass over the chest and localized self-trauma to the area.
      Repeated sternal trauma secondary to an improper wing trim was observed in this
      case before development of the lesion. Surgical excision of the mass was
      performed for diagnostic and treatment purposes. On histopathologic examination,
      the mass was characterized by well-differentiated trabecular bone surrounded by a
      thin layer of periosteum. These findings were consistent with, but not exclusive
      to, a diagnosis of osteoma. This benign bone lesion is rare in human and
      veterinary medicine, with even fewer reports of this condition in avian patients.
      Trauma to the sternum from falling because of wing clipping was the most likely
      inciting cause in this parrot.

PMID- 22458185
TI  - T-cell chronic lymphocytic leukemia in a double yellow-headed Amazon parrot
      (Amazona ochrocephala oratrix).
AB  - An adult, male double yellow-headed Amazon parrot (Amazona ochrocephala oratrix)
      was diagnosed with chronic lymphocytic leukemia based on results of a complete
      blood cell count and cytologic examination of a bone marrow aspirate. Treatment
      with oral chlorambucil was attempted, but no response was evident after 40 days.
      The bird was euthanatized, and the diagnosis of chronic lymphocytic leukemia was
      confirmed on gross and microscopic examination of tissues. Neoplastic lymphocytes
      were found in the bone marrow, liver, kidney, testes, and blood vessels. Based on
      CD3-positive immunocytochemical and immunohistochemical immunophenotyping, the
      chronic lymphocytic leukemia was determined to be of T-cell origin.

PMID- 22458186
TI  - Technology and the 21st century exotic animal veterinarian: positives and
      negatives.

PMID- 22458188
TI  - Safer passage.

PMID- 22458187
TI  - What is your diagnosis? Squamous cell carcinoma.

PMID- 22458189
TI  - The myths of bullying.

PMID- 22458190
TI  - Living alone is the new norm.

PMID- 22458191
TI  - Big gulp.

PMID- 22458192
TI  - AIDS memorial winner announced.

PMID- 22458193
TI  - Changes in blood glucose and insulin responses to intravenous glucose tolerance
      tests and blood biochemical values in adult female Japanese black bears (Ursus
      thibetanus japonicus).
AB  - The metabolic mechanisms to circannual changes in body mass of bears have yet to
      be elucidated. We hypothesized that the Japanese black bear (Ursus thibetanus
      japonicus) has a metabolic mechanism that efficiently converts carbohydrates into
      body fat by altering insulin sensitivity during the hyperphagic stage before
      hibernation. To test this hypothesis, we investigated the changes in blood
      biochemical values and glucose and insulin responses to intravenous glucose
      tolerance tests (IVGTT) during the active season (August, early and late
      November). Four, adult, female bears (5-17 years old) were anesthetized with 6
      mg/kg TZ (tiletamine HCl and zolazepam HCl) in combination with 0.1 mg/kg
      acepromazine maleate. The bears were injected intravenously with glucose (0.5
      g/kg of body mass), and blood samples were obtained before, at, and
      intermittently after glucose injection. The basal triglycerides concentration
      decreased significantly with increase in body mass from August to November. Basal
      levels of plasma glucose and serum insulin concentrations were not significantly
      different among groups. The results of IVGTT demonstrated the increased
      peripheral insulin sensitivity and glucose tolerance in early November. In
      contrast, peripheral insulin resistance was indicated by the exaggerated insulin
      response in late November. Our findings suggest that bears shift their glucose
      and lipid metabolism from the stage of normal activity to the hyperphagic stage
      in which they show lipogenic-predominant metabolism and accelerate glucose uptake
      by increasing the peripheral insulin sensitivity.

PMID- 22458194
TI  - Phylogenetic relationships of three species within the family Heligmonellidae
      (Nematoda; Heligmosomoidea) from Japanese rodents and a lagomorph based on the
      sequences of ribosomal DNA internal transcribed spacers, ITS-1 and ITS-2.
AB  - Nematodes of the family Heligmonellidae (Heligmosomoidea; Trichostrongylina)
      reside in the digestive tracts of rodents and lagomorphs. Although this family
      contains large numbers of genera and species, genetic information on the
      Heligmonellidae is very limited. We collected and isolated adult worms of three
      species in Japan that belong to the family Heligmonellidae, namely Heligmonoides
      speciosus (Konno, 1963) Durette-Desset, 1970 (Hs) from Apodemus argenteus,
      Orientostrongylus ezoensis Tada, 1975 (Oe) from Rattus norvegicus and
      Lagostrongylus leporis (Schulz, 1931) (Ll) from Pentalagus furnessi, and
      sequenced the entire internal transcribed spacer regions, ITS-1 and ITS-2 of
      ribosomal DNA. ITS-1 of Hs, Oe and Ll was 426, 468 and 449 bp in length, and had
      a G+C content of about 41, 41 and 37 %, respectively. ITS-2 of Hs, Oe and Ll was
      297, 319 and 276 bp in length and had a G+C content of about 38, 40 and 28%,
      respectively. The data of Hs, Oe and Ll were compared with those of two other
      known species within the family Heligmonellidae, Calorinensis minutus (Dujardin,
      1845) (Cm) and Nippostrogylus brasiliensis (Travassos, 1914) (Nb), and with those
      of two species of Heligmosomidae (Heligmosomoidea), Heligmosomoides polygyrus
      bakeri and Ohbayashinema erbaevae. Phylogenetic analysis placed Hs, Oe and Ll in
      the same clade with Cm and Nb, forming a Heligmonellidae branch in both ITS-1 and
      ITS-2, separate from the Heligmosomoidea branch. These results demonstrated that
      the ITS-1 and ITS-2 sequences are useful for differentiating the Heligmonellidae
      nematode species. This study is the first to describe the ITS-1 and ITS-2
      sequences of Hs, Oe and Ll.

PMID- 22458195
TI  - Examples and suggestions for the control of paratuberculosis in European cattle.
AB  - Paratuberculosis, or Johne's disease (JD), is caused by Mycobacterium avium
      subspecies paratuberculosis (MAP), is found in ruminants worldwide and can cause
      considerable economic losses in cattle. Control efforts and programs for JD in
      cattle are very diverse among European states, in Austria clinical JD is rated as
      a notifiable disease since 2006. The voluntary control programs established in
      many European countries, show different aims, measurements and acceptance. Most
      control programs for JD are based on a test and cull strategy, combined with
      hygienic precautions. Unfortunately, the willingness to participate in such
      programs by farmers and veterinarians is limited due to high costs, intensive
      workload, long duration and limited success. To overcome this drawback and to
      harmonize the control of MAP in Europe, a basic program with defined minimum
      standards is suggested. This "minimal program" for the control of JD in cattle
      consists of 3 steps. Step 1 includes diagnostic evaluation of every case of
      diarrhea in adult cattle and culling of animals with clinical JD. Step 2 is the
      implementation of basic management measures, adapted to the potentials of the
      individual farm. Step 3 consists of regularly evaluation of the MAP-herd status
      with the focus on MAP-shedding animals. This basic control program can be
      performed with reasonable costs and work load in most cattle herds and might
      serve as an international minimum standard for MAP-control in cattle. Such a
      program can also pose an incentive to decrease MAP-infections for those not
      willing to participate in more sophisticated control programs.

PMID- 22458196
TI  - Prevalence and prevention of paratuberculosis in North America.
AB  - The United States of America (U.S.) has made several attempts over the years to
      develop a producer accepted voluntary program. The focus of the U.S. Voluntary
      Bovine Johne's Disease Control Program (VBJDCP) is to provide producers with the
      tools to control Johne's disease on their farms and identify herds with a low
      risk for the presence of Mycobacterium avium subspecies paratuberculosis (MAP)
      infection. The VBJDCP includes an evaluation of producers' operations to identify
      practices that could allow the transmission of MAP among animals or between
      premises. Once risky practices havebeen identified, a herd management plan is
      developed to assist the producer in correcting risky practices. In addition to
      management changes, vaccination is a control tool allowed in the U.S. because it
      reduces the clinical signs of Johne's disease and the shedding of MAP. Testing is
      used in addition to management changes. While the classification component of the
      VBJDCP dictates the amount and type of testing herd owners are required to
      conduct, the education and management components of the VBJDCP does not specify
      testing protocols. The testing for control is intended to fit the needs and
      resources of producers and can be quite flexible. Management changes on the farm
      remain the key to control and programs cannot replace well thought out plans by
      producers that are specific to their resources, facilities, and operation.

PMID- 22458197
TI  - Epidemiological situation and control strategies for paratuberculosis in Japan.
AB  - Paratuberculosis (Ptb), caused by Mycobacterium avium subsp. paratuberculosis
      (Map), is a chronic and progressive granulomatous enteritis that affects many
      livestock and wild animals worldwide. The clinical disease is called Johne's
      disease (JD). In Japan, all dairy cattle (harf million head) are examined for Ptb
      every five years. About 1000 the officially examined cattle are diagnosed
      annually as positive for Ptb, but most of these exhibit only minor or no clinical
      signs and typical lesions in recent years. In contrast to the situation in Japan,
      the disease prevalence in western countries is very high. We have used ELISA and
      a culture examination of Map, and recently real-time PCR to diagnose this
      disease. In this review, the author outlines the history of the epidemic and
      national practical strategies to control paratuberculosis in Japan.

PMID- 22458198
TI  - BVDV control and eradication in Europe--an update.
AB  - Infections with bovine viral diarrhoea virus (BVDV) are endemic in cattle
      populations worldwide and result in major economic losses. For long, attempts to
      control BVDV were limited to prophylactic vaccination practices, implemented
      primarily to reduce or prevent clinical disease on a herd basis. However, the
      benefit of preventing clinical disease in transiently infected animals is
      negligible when considering the overall losses of the disease. Another more
      systematic strategy to control evolved during the 1990s within eradication
      programmes in the Scandinavian countries. This was based on an initial
      determination of herd BVDV status, followed by implementation of systematic zoo
      sanitary measures at a regional or national scale (without the use of vaccines)
      to prevent introduction of BVDV in non-infected herds, and to reduce the
      prevalence of infected herds by identification and elimination of PI animals.
      These programmes have been very successful, and all of the Scandinavian countries
      are currently either free, or almost free from BVDV. Today control programmes are
      underway in several European countries. This short review discusses the general
      model of BVDV control, and gives an overview of strategies used within, and the
      current status of, the ongoing control programmes in Europe.

PMID- 22458199
TI  - Preventive strategy for BVDV infection in North America.
AB  - Despite 60 years of vaccination, bovine viral diarrhea virus (BVDV) infections
      remain a source of significant economic loss for producers in the United States.
      Control program design in the United States varies by region based on the
      incidence of BVDV, density of animal populations, animal movement, contact with
      wildlife populations, level of producer compliance, variation among circulating
      BVDV strains, prevalent type of production unit or industry and support offered
      by state institutions. The Upper Peninsula BVDV Eradication Program in Michigan,
      the Montana BVD-PI Herd Biosecurity Project, the Washington State BVDV Testing
      program and the Alabama Voluntary BVD Control Program illustrates four different
      regional approaches. All four programs are voluntary rather than government
      mandated and a large component of each was the identification and removal of
      animals persistently infected with BVDV. The Washington, Montana and Alabama
      programs focus on herd screening to eliminate PI's but did not have eradication
      as a goal. The Michigan program was unique in that its goal was to eradicate BVDV
      from a defined geographic region. While the Washington, Alabama and Montana
      programs were beneficial to individual producers they did not have a significant
      impact on the prevalence of BVDV. In contrast, the Michigan program has reduced
      incidence of herds harboring PI animals in the region. Organizers of all four
      programs noted that compliance with control programs was directly linked to
      education and the presence of a support network composed of fellow producers,
      engaged veterinarians and knowledgeable diagnosticians.

PMID- 22458200
TI  - Neosporosis in dairy cattle.

PMID- 22458201
TI  - Prevalence of leptospirosis in farm animals.

PMID- 22458202
TI  - Practicing in dreams can improve your performance.

PMID- 22458203
TI  - Coming through when it matters most.
AB  - All teams would like to think they do their best work when the stakes are highest
      when the company's future or their own rests on the outcome of their projects.
      But too often something else happens. In extensive studies of teams at
      professional service firms, Harvard Business School's Gardner has seen the same
      pattern emerge over and over: Teams become increasingly concerned with the risks
      of failure rather than the requirements of excellence. As a result, they revert
      to safe, standard approaches instead of delivering original solutions tailored to
      clients' needs. Gardner has a name for this phenomenon: the performance pressure
      paradox. Here's how it develops: As pressure mounts, team members start driving
      toward consensus in ways that shut out vital information. Without even realizing
      it, they give more weight to shared knowledge and dismiss specialized expertise,
      such as insights into the client's technologies, culture, and aspirations. The
      more generically inclined the team becomes, the more concerned the client grows,
      which turns up the pressure and pushes the team even further down the generic
      road. But forewarned is forearmed. By measuring each person's contribution
      deliberately, ruthlessly insisting that no one's contribution be marginalized,
      and framing new information within familiar contexts, teams can escape the
      performance pressure paradox and keep doing their best work when it matters most.

PMID- 22458204
TI  - The real leadership lessons of Steve Jobs.
AB  - The author, whose biography of Steve Jobs was an instant best seller after the
      Apple CEO's death in October 2011, sets out here to correct what he perceives as
      an undue fixation by many commentators on the rough edges of Jobs's personality.
      That personality was integral to his way of doing business, Isaacson writes, but
      the real lessons from Steve Jobs come from what he actually accomplished. He
      built the world's most valuable company, and along the way he helped to transform
      a number of industries: personal computing, animated movies, music, phones,
      tablet computing, retail stores, and digital publishing. In this essay Isaacson
      describes the 14 imperatives behind Jobs's approach: focus; simplify; take
      responsibility end to end; when behind, leapfrog; put products before profits;
      don't be a slave to focus groups; bend reality; impute; push for perfection; know
      both the big picture and the details; tolerate only "A" players; engage face-to
      face; combine the humanities with the sciences; and "stay hungry, stay foolish."

PMID- 22458205
TI  - Wilderness leadership--on the job.
AB  - Lessons taught and learned in the challenging, unpredictable environment of a
      wilderness expedition have direct applications to today's business world. That's
      according to two directors at the National Outdoor Leadership School, who in this
      article share five principles for expedition--and career-success. (1) Practice
      leadership. The fundamental philosophy of NOLS is that leadership can be learned
      even by those who don't think they have a natural ability to lead. You just need
      to practice making decisions, then reflecting on and learning from the outcomes.
      (2) Lead from everywhere. In an expedition group, or in an organization, you can
      play four roles, often simultaneously: designated leader, active follower, peer
      leader, and self-leader. Effective teamwork rests on knowing how and when to step
      into each role. (3) Behave well Leadership means getting along in a diverse
      group, cooperating with teammates, effectively resolving conflict, and keeping
      yourself and others motivated. (4) Keep calm. On expeditions and in business,
      people often end up scrapping not only Plan A but also Plan B. Leadership
      involves planning for things you can control, letting go of things you can't,
      expecting the unexpected, and maintaining composure when unforeseen circumstances
      arise. (5) Disconnect to connect. The fast-paced, high-tech world of work wreaks
      havoc on leaders' ability to engage in the careful, strategic thinking required
      of them. It's important to disconnect from 21st-century distractions and to
      connect with nature once in a while.

PMID- 22458206
TI  - Genetic diversity and structure of wild populations of the tropical dry forest
      tree Jacaratia mexicana (Brassicales: Caricaceae) at a local scale in Mexico.
AB  - The tropical dry forest is a greatly endangered ecosystem, from which Jacaratia
      mexicana is a native tree. With the aim to assess the levels of genetic variation
      and population structure, four wild populations of J. mexicana were studied in
      the Sierra de Huautla Biosphere Reserve, Morelos, Mexico. For this, DNA was
      extracted from 159 individuals and were amplified with six random primers using
      the Random Amplified Polymorphic DNA (RAPD). A total of 54 bands were obtained,
      of which 50 (92.6%) were polymorphic. The total genetic diversity found within
      the four populations was 0.451 when estimated by Shannon's index. An AMOVA
      analysis showed that 84% of the total genetic variation was found within
      populations and 16% was among populations. The UPGMA dendrogram showed that all
      individuals from one of the populations (Huaxtla) formed one distinct genetic
      group, while the rest of the individuals did not cluster according to population.
      A Mantel test did not show an association between genetic and geographical
      distances among populations (r=0.893, p=0.20). A Bayesian cluster analysis
      performed with STRUCTURE, showed that the most probable number of genetic groups
      in the data was four (K=4), and confirmed the distinctness of Huaxtla population.
      Our results showed that important genetic differentiation among populations can
      occur even at this small geographic scale and this has to be considered in
      conservation actions for this genetic resource.

PMID- 22458207
TI  - Changes in structure and composition of evergreen forests on an altitudinal
      gradient in the Venezuelan Guayana shield.
AB  - There have been several ecological studies in forests of the Guayana Shield, but
      so far none had examined the changes in structure and composition of evergreen
      forests with altitude. This study describes and analyzes the structure, species
      composition and soil characteristics of forest stands at different altitudinal
      zones in Southeastern Venezuelan Guayana, in order to explain the patterns and
      the main factors that determine the structure and composition of evergreen
      forests along the altitudinal gradient. Inventories of 3 948 big (>10cm DBH) and
      1 328 small (5-10cm DBH) woody stems were carried out in eleven plots, ranging
      from 0.1 to 1.0ha, along a 188km long transect with elevations between 290 and 1
      395masl. It has been found that 1) hemiepihytes become more dominant and lianas
      reduce their dominance with increasing altitude and 2) the forest structure in
      the study area is size-dependent. Five families and 12 genera represented only 9%
      of the total number of families and genera, respectively, recorded troughout the
      gradient, but the two groups of taxa comprised more than 50% of the Importance
      Value (the sum of the relative density and the relative dominance) of all
      measured stems. Moreover, the results suggest that low species richness seems to
      be associated with the dominance of one or few species. Stand-level wood density
      (WD) of trees decreased significantly with increasing elevation. WD is an
      indicator of trees'life history strategy. Its decline suggests a change in the
      functional composition of the forest with increasing altitude. The Canonical
      Correspondence Analysis (CCA) indicated a distinction of the studied forests on
      the basis of their altitudinal levels and geographic location, and revealed
      different ecological responses by the forests, to environmental variables along
      the altitudinal gradient. The variation in species composition, in terms of basal
      area among stands, was controlled primarily by elevation and secondarily by
      rainfall and soil conditions. There are other interacting factors not considered
      in this study like disturbance regime, biological interactions, productivity, and
      dispersal history, which could affect the structure and composition of the
      forests in the altitudinal gradient. In conclusion, it appears that the
      structural and floristic variability observed in the studied transect is produced
      by a combination of different climates and randomly expressed local processes
      interacting across a complex physical landscape.

PMID- 22458208
TI  - [Plant communities in the terrestrial-aquatic transition zone in the paramo of
      Chingaza, Colombia].
AB  - Plant communities in the terrestrial-aquatic transition zone in the paramo of
      Chingaza, Colombia. High Andean paramo ecosystems are an important water resource
      for many towns, and major cities in this region. The aquatic and wetland
      vegetation of different paramo lakes, pond, swamps and bogs was studied according
      to the classical phytosociological approach, which is based on homogenous stands,
      but excludes any border phenomena or transitional zone. The present research
      aimed at determining the aquatic and wetland vegetation along different moisture
      gradients. A total of 89 species in 30 transects were reported, of which Crassula
      venezuelensis, Carex honplandii, Callitriche nubigena, Eleocharis macrostachya,
      Ranunculus flagelliformis, R. nubigenus, Eleocharis stenocarpa, Galium ascendens
      y Alopecurus aequalis were present in more than one third of the transects.
      Numerical classification and indicator species analysis resulted in the
      definition of the next 18 communities: 1) Calamagrostis effusa, 2) Sphagnum
      cuspidatum, 3) Cyperus rufus, 4) Eleocharis stenocarpa, 5) Carex acutata, 6) Poa
      annua,7) Valeriana sp., 8) Ranunculus flagelliformis, 9) Carex bonplandii, 10)
      Festuca andicola. 11) Muhlenbergia fustigiata, 12) Elatine paramoana, 13) Isoetes
      palmeri, 14) Crassula venezuelensis, 15) Lilaeopsis macloviana, 16) Callitriche
      nubigena, 17) Potamogeton paramoanus and 18) Potamogeton illinoensis. The
      ordination of communities reveals the presence of three different aquatic
      terrestrial gradients which are related to the life form structure of species
      that characterized the various communities. We concluded that patchiness and
      heterogeneity of the vegetation is mainly the result of alterations caused by
      human activities (burning, cattle raise and material extraction for road and dam
      construction).

PMID- 22458209
TI  - Effect of artificial feeders on pollen loads of the hummingbirds of Cerro de la
      Muerte, Costa Rica.
AB  - Although sugar-water feeders are commonly used by enthusiasts to attract
      hummingbirds, little is known about how they affect hummingbird behavior and
      flower use. We studied the highland hummingbird assemblage of Cerro de La Muerte,
      Costa Rica, both at a site with permanent feeders (La Georgina Restaurant) and
      further from it. We examined how feeder use and monopolization affected seasonal
      changes in pollen loads during four sampling periods, including dry and wet
      seasons, from 2003-2005. We expected that species monopolizing the feeders would
      carry little or no pollen whatsoever, and would have pollen loads characterized
      by low floral diversity, in contrast with species less dependent on feeders. We
      obtained pollen samples from 183 individuals of four hummingbird species captured
      around the feeders using mist nets, which were compared with a pollen reference
      collection of plants with a pollination syndrome by hummingbirds. The same
      methods were implemented at a site 3km away from the feeders. Feeder usage was
      quantified by counting the number of times hummingbirds drank from the feeders in
      periods of 4min separated by 1min. The effects of hummingbird species and season
      on pollen load categories were assessed using a nominal logistic regression. The
      alpha species at the site, the Fiery-throated Hummingbird (Panterpe insignis),
      dominated the feeders during the dry season. Meanwhile, in the wet season, feeder
      usage was more evenly distributed across species, with the exception of the
      Volcano Hummingbird, Selasphorus flammula, which occupies the last place in the
      dominance hierarchy. Pollen loads of hummingbirds captured near feeders were low
      in abundance (more than 50% of captured individuals had zero or low pollen
      loads), and low in species richness (96% of the hummingbirds with pollen from
      only one plant genus, Centropogon). Overall pollen loads increased during the dry
      season coinciding with peaks in flower availability, although the majority of
      captured hummingbirds carried no pollen. Mist nets located 3km from La Georgina
      returned few captures (one-to-three specimens) per sampling date, contrasting
      with observations made before feeders were present. These results suggest that
      sugar-water feeders gather hummingbirds in over considerable distances drawing
      them away from flowers. The competitive and antagonistic pattern shown between
      feeders and flowers indicate that natural pollination system could be
      significantly altered. Supplementing hummingbirds with food seems likely to
      interfere with pollination networks already stressed by many anthropogenic
      effects.

PMID- 22458210
TI  - [Morphological evidence of hybridization between Ramphocelus flammigerus
      subspecies (Passeriformes: Thraupidae) in Colombia].
AB  - Habitat modifications such as deforestation and the increase of agricultural
      activities, have led to uncommon faunal interactions. In Colombia, this condition
      have caused the secondary contact of subspecies of Ramphocelus flammigerus
      populations from Cauca valley and the Pacific coast; and some specimens with
      rumps of intermediate colors of the subspecies have been found and are thought as
      hybrids. The objective of this study was to assess the presence of morphological
      evidence that may suggest hybridization and may explain the origin of individuals
      with intermediate coloration. We predict that if subspecies hybridize, they will
      be more similar in morphology when coexisting than when separated. Alternatively,
      coexisting subspecies might diverge in sympatry, because of selection to reduce
      competition for resources (character displacement). For this, a survey in 15
      localities was undertaken: 10 allopatric areas (five for each subspecies), and
      five sympatric areas. Mist nets were used to capture individuals and a total of
      seven morphological characters were measured. To identify the patterns of
      morphological variation, we compared morphology of subspecies, sympatric and
      allopatric populations and individuals of intermediate colors. Consequently, we
      performed discriminant analysis and test for differences between groups by using
      95% confidence intervals for log-ratio tests. A total of 112 individuals were
      captured (46 intermediate-colored individuals, 20 R. f. flammigerus, and 46 R.f.
      icteronotus. Discriminant analyses showed that subspecies were well
      differentiated, and intermediate individuals overlapped with them. Log-ratio
      test, based on Mahalanobis distances, showed that intermediate individuals were
      morphologically more similar to both subspecies than subspecies themselves. In
      addition, log-ratio tests showed that subspecies sympatric populations were
      similar but allopatric ones were different, and that individuals of intermediate
      colors were more similar to sympatric than to allopatric populations of the two
      subspecies. Therefore, morphological evidence supports the predictions of a
      hybridization hypothesis among the subspecies of R. flammigerus. In conclusion,
      the analysis of morphological variation in R. flammigerus suggests that
      hybridization between subspecies is occurring and that a process of genetic
      introgression is probably in progress.

PMID- 22458211
TI  - Prosopis laevigata and Mimosa biuncifera (Leguminosae), jointly influence plant
      diversity and soil fertility of a Mexican semiarid ecosystem.
AB  - Prosopis laevigata and Mimosa biuncifera are frequently found in arid and
      semiarid shrublands, but scarce information is available about their influence on
      plant community structure and soil fertility. We compared plant community
      structure, diversity and soil nutrients of three semiarid shrubland sites located
      in Mezquital Valley, Mexico. These sites differ in their dominant species: Site 1
      (Bingu) P. laevigata, Site 2 (Gonzalez) M. biuncifera, and Site 3 (Rincon) with
      the presence of both legumes. The results showed that the plant community with P.
      laevigata and M. biuncifera (Site 3) had more cover, taller plants and higher
      plant diversity than sites with only one legume (Site 1 and Site 2). Soil organic
      matter (SOM), soil organic carbon (SOC), total nitrogen (TN), phosphorus-Olsen
      (P) and C mineralization were higher in the soil under the canopy of both legumes
      than in bare soil. In contrast, soil cation concentrations were lower under the
      canopy of P. laevigata, but not for M. biuncifera. In addition, the density of
      arbuscular mycorrhizal fungi spores was higher within the soil under the canopy
      of M. biuncifera than in the soil under the canopy of P. laevigata. Thus,
      resource islands (RI) created by P. laevigata increased the amounts of SOC, TN
      and P when compared with the RI of M. biuncifera. This study provided evidences
      about the importance of species identity in order to expand the niche
      availability for the establishment of other plants, and highlights that P.
      laevigata and M. biuncifera jointly influencing plant colonization within
      semiarid ecosystems.

PMID- 22458212
TI  - Mechanisms of Oryza sativa (Poaceae) resistance to Tagosodes orizicolus
      (Homoptera: Delphacidae) under greenhouse condition in Venezuela.
AB  - Tagosodes orizicolus is one of the main plagues of rice in tropical America
      causing two types of damages, the direct one, feeding and oviposition effect, and
      an indirect one, by the transmission of the "Rice hoja blanca virus". During 2006
      2007 we carried out research under greenhouse conditions at Fundaci6n Danac,
      Venezuela, in order to determine the mechanisms of antixenosis, antibiosis and
      tolerance to T. orizicolus, which could be acting in commercial varieties and
      advanced lines of the rice genetic breeding programs of INIA and Fundaci6n Danac.
      The method of free feeding was used for the antixenosis evaluation, whereas the
      method of forced feeding was used for antibiosis evaluation (effect on survival
      and oviposition). Additionally, we used the indirect method based on biomass
      depression to estimate the tolerance. Some of the evaluated traits included:
      grade of damage, number of insects settling on rice plants, percentage of sogata
      mortality at the mature state, number of eggs in the leaf midrib and an index of
      tolerance. The results showed that rice genotypes possess different combinations
      of resistance mechanisms, as well as different grades of reactions. The
      susceptible control 'Bluebonnet 50' was consistently susceptible across
      experiments and the resistant control 'Makalioka' had high antixenosis and high
      antibiosis based on survival and oviposition. The rest of the genotypes presented
      lower or higher degrees of antixenosis and antibiosis for survival and
      oviposition. The genotype 'FD0241-M-17-6-1-1-1-1' was identified with possible
      tolerance to the direct damage of sogata.

PMID- 22458213
TI  - [Thysanoptera (Insecta)-Vicia faba (Fabaceae) association in Prepuna and Puna in
      Jujuy, Argentina].
AB  - The different phenological stages of Vicia faba provide food resources and
      substrates for the development of a significant diversity of insects. This study
      aimed to identify the complex of anthophyllous thrips, analyze the species
      population fluctuations, to obtain some bioecological aspects and the role they
      play in this association. The study and sampling was conducted during the
      flowering-fruiting bean crop stages in two phytogeographical regions of Jujuy:
      Prepuna (2 479m asl) on a weekly basis, from October-December 1995-1996 and Puna
      (3 367m asl) every two weeks, from December 2007-March 2008. Each sample
      consisted of 25 flowers taken at random; only at Prepuna a complementary sampling
      of three hits per plant (n=10 plants) was conducted. Observations were made on
      oviposition sites, admission to the flower, pupation sites, feeding behavior and
      injuries caused. In Prepuna, the Thysanoptera complex consisted of Frankliniella
      australis, F. occidentalis, F. gemina, F. schultzei and Thrips tabaci; in Puna,
      the specific diversity was restricted to F. australis and F. gemina. Although the
      planting-harvest period in both areas did not match, the fluctuations in
      populations showed the same pattern: as flowering progressed, the number of
      thrips coincided with the availability of food resources. In both areas, F.
      australis was the dominant species and maintained successive populations; it
      layed eggs in flower buds, and larvae hatched when flowers opened; feeding larvae
      and adults brought about silvery stains with black spots. In Prepuna, F.
      australis went through the mobile immature stages on flowers, while quiescent
      stages were on the ground; in the Puna, all development stages took place within
      the flowers. Thrips tabaci, F. shultzei, F. occidentalis and F. gemina were
      temporary and opportunistic in Prepuna, while the presence of F. gemina was
      sporadic in Puna. The number of Thysanoptera species associated with beans
      cultivation in Argentina has increased.

PMID- 22458214
TI  - Costa Rica's Marine Protected Areas: status and perspectives.
AB  - With 51 100km2 of terrestrial area and 589 000km2 of national waters, Costa Rica
      is considered one of the countries with the greatest biodiversity. It has
      approximately 3.5% of the world marine species. In the last four decades, Costa
      Rica has done a considerable effort to create a representative system of
      Protected Areas (PA), mainly terrestrial. We present an assessment of the current
      situation of the Marine Protected Areas (MPA) in Costa Rica, through an
      historical analysis, and an evaluation of their distribution, coverage and
      management categories. Costa Rica has 166 protected areas covering 50% of the
      coastline; of these 20 are MPAs, classified as National Parks (90.6%), National
      Wildlife Refuges (6.6%), Wetlands (1.5%), Biological Reserves (1%), and one
      Absolute Natural Reserve (0.3%). According to IUCN criteria, 93.7% correspond to
      category II, 5% to IV and 1.3% to I. The marine protected surface is 5 296.5km2,
      corresponding to 17.5% of the territorial waters and 0.9% of the Exclusive
      Economic Zone. The median distance between MPAs is 22.4km in the Pacific and
      32.9km along the Caribbean. The median size is close to 54km2. The main threats
      to MPAs are the lack of coordination between governmental agencies, limited
      economic resources, restricted patrolling and control, poor watershed management,
      and rampant coastal alteration.

PMID- 22458215
TI  - Successional pattern of phytoplankton (>55 microm) in Lekki lagoon, Nigeria.
AB  - Lagoons are dominant features along large stretches of the West Africa coast.
      These freshwater environments are very valuable areas where phytoplankton
      constitute the basis of aquatic food webs. In order to know the effects of
      environmental variables on phytoplankton, a study of the successional pattern of
      phytoplankton in Lekki lagoon was carried out monthly for two years (June 2003
      May 2005). Phytoplankton samples were collected from 12 stations using a plankton
      net of 55 microm mesh, and samples preserved in 4% unbuffered formalin. Besides,
      surface water samples were taken for physico-chemical analysis. For each year,
      the seasonal distribution and succession of dominant phytoplankton followed
      different patterns. Phytoplankton abundance was higher during the dry season
      (November-April) for the two annual cycles. The diatoms (Aulacoseira granulata
      and A. granulata var angustissima) and blue green algaes, Microcystis aeruginosa,
      Merismopedia tennuissima and Trichodesmium lacustre showed this trend by being
      the abundant species in some of these months. For the rainy season, the green
      alga Mougeotia sp. dominated. The replacement of one form by another throughout
      seasonal cycles was probably controlled by the changes in environmental variables
      such as rainfall, nitrate-nitrogen and phosphate-phosphorus.

PMID- 22458216
TI  - [Seasonal variations of community structures phytoplankton in groundwater
      discharge areas along the Northern Yucatan Peninsula coast].
AB  - The highly touristic Yucatan Peninsula is principally constituted with coastal
      marine environments. Like other coastal areas, this has been affected by the
      increase of waste water discharge, hydrological modifications and land use
      changes in the area. The phytoplankton community structure is one of the main
      components of coastal ecosystems and the most affected in hydrological processes.
      In order to follow the seasonal variations, the phytoplankton was characterized
      to follow the hydrological variability in two sites (Dzilam and Progreso) of the
      Northern Yucatan Peninsula. For this, cruises were carried out monthly during one
      year, from April 2004 to March 2005, with two samplings per season (dry, rainy
      and "nortes"). Hydrological variability was associated with seasonality and
      directly linked to groundwater discharges in the Dzilam area, and waste water
      discharges in the Progreso area. The highest nutrient concentrations occurred
      mainly during the rainy season. The phytoplankton community changes observed
      throughout the year suggested that the hydrological and chemical variability
      associated with seasonality and anthropogenic impacts have a strong influence.
      The substitution of diatoms by dinoflagellates as the dominant group in Progreso
      was the result of seasonal variability itself, but also could have been caused by
      eutrophic processes; while in Dzilam, the major presence of diatoms could have
      been favored by groundwater discharges. The results of this study can be used to
      understand the linkages between stressors from the anthropogenic activities and
      coastal water quality and changes.

PMID- 22458217
TI  - Bloom of Gymnodinium catenatum in Bahia Santiago and Bahia Manzanillo, Colima,
      Mexico.
AB  - Gymnodinium bloom events are of concern, since they produce toxins, which have
      unfavorable consequences to marine ecosystems, human health and the economy. This
      report describes the physico-chemical conditions that were present during the
      algal bloom event on May 2010 in Bahia Manzanillo and Bahia Santiago, Colima,
      Mexico. For this, seawater nutrient analysis, phytoplankton counts,
      identification, and toxicity tests were undertaken. Nutrients in seawater were
      determined using colorimetric techniques, the higher concentrations (8.88 microM
      DIN, 0.78 microM PO4 and 24.34 microM SiO2) were related with upwelling waters
      that promoted the algal bloom that began after registering the year lowest sea
      surface temperature, favoring the rapid growth of G. catenatum (up to 1.02 x
      10(7) cells/L). Phytoplankton counting was carried out using sedimentation
      chambers and cells enumerated on appropriated area. The bloom persisted in the
      bays for approximately two weeks and was associated with toxicity (determined
      with HPLC) in local oysters (1525.8 microg STXeq/100g), and in phytoplankton
      (10.9 pg STXeq/cells) samples. Strong variations in cell toxicity (1.4 to 10.9pg
      STXeq/cells), most likely reflected the availability of inorganic nutrients. The
      toxin profile of the phytoplankton samples consisted of 11 toxins and resembled
      those recorded for several strains of G. catenatum isolated from other coastal
      areas of Mexico.

PMID- 22458218
TI  - Distribution of some calanoida (Crustacea: Copepoda) from the Yucatan Peninsula,
      Belize and Guatemala.
AB  - Southern Mexico and Central America have many water bodies of different
      morphology and water chemistry with an interesting zooplankton fauna, originating
      from North or South America. A set of 63 samples, taken in 2005 and 2008, from
      water bodies of the Yucatan Peninsula karst, Belize and Guatemala, were studied
      for the content of calanoid copepods. Old and recent literature was used to
      determine animals to species level. Drawings were prepared with a microscope and
      a camera lucida. A total of 32 samples with totally six species contained
      calanoid copepods: one estuarine pseudodiaptomid and five freshwater diaptomids.
      Pseudodiaptomus marshi was found at different salinities. It is confirmed that
      the commonest diaptomids in the Yucatan Peninsula are Arctodiaptomus dorsalis and
      Mastigodiaptomus nesus. The former was also recorded from Lake Amatitlan.
      Mastigodiaptomus nesus is as widespread as A. dorsalis but it is absent from the
      Lake Peten area in Guatemala. Mastigodiaptomus reidae was found in two shallow
      habitats, these specimens differ from those from the type locality by having a
      set of peculiar large spine-like processes on the last thoracic and the urosome
      segments of the females. Leptodiaptomus siciloides was found only in Lake Ayarza
      with high salinity. Prionodiaptomus colombiensis occurred in the highlands of
      Guatemala in Lago de Guija and in the Peten area in Laguna Sacpuy. We contributed
      with our occurrence records to a better knowledge of the geographic distribution
      of some calanoid copepods. Morphological findings in some species are of value
      for taxonomic differentiation between species.

PMID- 22458219
TI  - [The fisheries and growth of Ark Clams (Arcoida: Arcidae) Anadara tuberculosa in
      Malaga Bay, Colombian Pacific, 2005-2007].
AB  - A. tuberculosa, is the most important bivalve species under exploitation in
      Colombia. Here, this species is found from Cabo Corrientes (Choco) to the Ecuador
      border, in muddy substrates of mangrove forests. In order to determine the growth
      and the state of fisheries of A. tuberculosa, between December 2005 and April
      2007, both, biological (in situ) and commercial studies were performed at Bahia
      Malaga (Colombian Pacific). The growth was estimated using the general equation
      of von Bertalanffy, with prior application of the methods of Bhattacharya and
      Powell-Wetherall. Mortality and exploitation rate were determined using the
      inverse model of von Bertalanffy. For the biological samplings, a total of 446
      individuals of A. tuberculosa (0.64 +/- 0.13 individuals/m2) and 53 individuals
      (0.05 +/- 0.049 individuals/m2) of Anadara similis were collected. 79% of the
      catch was below 51mm. In the commercial samplings, 836 individuals of A.
      tuberculosa (size range: 31.1-92.2mm) were measured, but no A. similis samples
      were available for this. Recruitment of A. tuberculosa was higher during March,
      May, July and November. According to the data, A. tuberculosa might be
      reproducing during December, February, April and August. The data gathered with
      the biological samples were more reliable on explaining the growth of A.
      tuberculosa (K=0.332 per year, L(infinity)=88.256mm, t0=0.0556 years) than the
      one taken from market samples (K=0.256 per year, L(infinity)=89.77mm, t0=0733
      years). The high exploitation rate (77%), the low density and the high mortality
      suggest that A. tuberculosa is in overexploitation state in Bahia Malaga and
      management strategies are urgently required.

PMID- 22458220
TI  - [Distribution of the mangrove gastropods Neritina virginea (Neritidae) and
      Littoraria angulifera (Littorinidae) within the Colombian Caribbean Darien
      Ecoregion].
AB  - Gastropods are one of the most abundant groups within the Caribbean mangroves,
      however, little is known about the distribution of particular species at a
      regional scale. With this aim, we studied the geographic distribution of
      Littoraria (Littorinopsis) angulifera and Neritina (Vitta) virginea within the
      Darien Ecoregion in the Caribbean coast of Colombia, from 77 sampling stations
      along 609km between the Colombian-Panama border and Cordoba State, Colombia. The
      fieldwork was conducted in June-August 2009, and a total of 3 963 individuals of
      both species were hand-picked from the ground, prop-roots and trunks along 50m
      transects, and shell sizes were measured. The description of geographic patterns
      considered surface water salinity, mangrove cover and gastropod distribution
      within the Gulf of Uraba. In the outer-most part of the Gulf, L. angulifera was
      present in 84.8% of the stations, while N. virginea was only present in 15.2% of
      the stations. In this part, mangroves areas were patchily distributed, and the
      gastropods (mainly L. angulifera) were found on woody debris along the
      supralittoral zone in sandy shores. In the inner-most part, in contrast, N.
      virginea occurred in 84.6% of the stations, mostly in estuaries, deltas and river
      margins, while L. angulifera only appeared in Turbo Bay (15.4%). Mean shell size
      also exhibited a clear geographic pattern: size range was 6-22mm in L.
      angulifera, and 6-12mm in N. virginea. L. angulifera was found in open-water
      stations with water salinities >10PSU, but it was absent in sites with lower
      salinities like the Atrato River Delta and other small rivers. Its presence on
      coastal woody debris suggests that despite of the recruitment of small
      individuals from the nearshore stock of larvae, populations are unable to
      establish due to the absence of mangroves protection. Oppositely, N. virginea was
      found under estuarine conditions on mangrove roots and ground. Our results
      confirm that L. angulifera is an esteno-tolerant marine species, and N. virginea
      is an eury-tolerant estuarine species, thus their geographic distribution is
      strongly shaped by the large freshwater discharge of the Atrato River. We
      hypothesize that absence or limited distribution of gastropods in various areas
      of the Darien Ecoregion may be further explained by the poor conservation state
      of mangroves.

PMID- 22458221
TI  - [Hermit crabs (Anomura: Paguroidea) distribution patterns in the Colombian
      Caribbean Sea].
AB  - Hermit crabs represent the marine life in the Colombian Caribbean, and are
      important for the dynamic equilibrium maintenance in ecosystems, the ecological
      interactions and their impact on food web stability. Generally, in order to come
      up with some conservation strategies, strong bio-geographical information is
      needed for poll cies definition. With this aim, this study analyzed the
      distribution patterns of hermit crabs in the Colombian Caribbean Sea. through
      classification and spatial ordination multivariate analyses, using historical
      records from years 1916 to 2006. Besides, the world distribution of Colombian
      species and their geographic affinity in the Caribbean and Western Atlantic were
      identified. The results show deep differences between coastal and continental
      slope faunas, and latitudinal differences in the assemblages, with the
      identification of three groups: Northeast. Center and Southwest. The differences
      in faunal composition that support these three groups were determined. Based on
      maps of the Colombian marine ecosystems, it was found that the main factors
      affecting the distribution of hermit crabs were the Caribana slope (depth), water
      mass temperature, Guajira sea-grass beds, and particular conditions of "Coralline
      Archipelagos" and "Darien" eco-regions. Colombian hermit crab fauna is more
      related to the North Atlantic and the Antilles, than to the South Atlantic and
      the Gulf of Mexico. Additionally, geographical sub-provinces in which Colombia is
      included, these were found as transition zones among Northern and Austral
      subprovinces of the Greater Caribbean.

PMID- 22458222
TI  - Vitellogenin levels in hemolymph, ovary and hepatopancreas of the freshwater
      crayfish Cherax quadricarinatus (Decapoda: Parastacidae) during the reproductive
      cycle.
AB  - The freshwater crayfish Cherax quadricarinatus is a tropical species of great
      interest for aquaculture. Vitellogenin (Vg), a lipoprotein precursor of the
      vitellum accumulated in spawned eggs, can be synthesized in the ovary and/or
      hepatopancreas of most crustaceans, being the hemolymph the way for transporting
      Vg throughout the reproductive cycle. Concentration of Vg in hemolymph, ovary and
      hepatopancreas of Cherax quadricarinatus adult females was measured by means of
      ELISA, specifically developed after purifying the native Vg. Measurements were
      made at four periods of the reproductive cycle: pre-reproductive, mid
      reproductive, late reproductive and post-reproductive. Besides, both
      hepatosomatic (HSI) and gonadosomatic (GSI) indexes were determined in each
      period. Significant variations in Vg levels were detected in both hemolymph and
      hepatopancreas, being the highest values observed during the mid-reproductive
      period. Besides, such variations were positively correlated to the HSI. A
      positive correlation between Vg levels in hepatopancreas and ovary was also seen.
      These results support previous evidences about the central role of the
      hepatopancreas as a site of Vg synthesis in the studied species, together with
      the relevancy of hemolymph for transporting Vg from the hepatopancreas to the
      ovary. For aquaculture purposes, Vg monitoring in hemolymph could be used as a
      non-injurious method, to check the reproductive activity of C. quadricarinatus
      females.

PMID- 22458223
TI  - [Variations of the nutritional condition of lobsters Panulirus argus (Decapoda:
      Palinuridae) in Eastern region of the Gulf of Batabano, Cuba].
AB  - Nutritional condition can affect survival and growth rate of crustaceans, and
      this is mostly affected by habitat conditions. This study describes the space
      temporary nutritional changes in this commercially important species. With this
      aim, the variations in the nutritional condition (K) of lobsters from four zones
      (1, 2, 4 and 5) in the Gulf of Batabano, Cuba, were determined. For this, the
      weight/length ratio (K=Pt/Lt) was calculated using animals captured in 1981 and
      2010. The nutritional condition between areas and sexes, and years and sexes, was
      contrasted by a bifactorial ANOVA, and the overall length and weight of lobsters
      were compared using a t-Test for independent samples and unifactorial ANOVA. It
      was found that the nutritional condition was significantly greater in males than
      in females. In addition, significant variations between zones were detected for
      both years. Nutritional condition of lobsters from Zone five was the highest for
      1981, while it was Zone two for 2010. Lobsters nutritional state showed
      significant variations between years, being greater in 1981 (2.34 +/- 0.84g/mm)
      than in 2010 (1.96 +/- 0.49g/mm). The inter-zones variations as well as the inter
      annual ones seem to be related to the reported variations of the bottom type and
      the vegetation cover. Seasonal variations in the abundance and distribution of
      benthic organisms, that constitute food for lobsters, could also be influencing.
      The differences between sexes, however, were assumed as a consequence of the
      methodology used and the sexual dimorphism of the species. Due to other K
      estimation methods, that do not include morphometric measurements, these
      differences were not detected. We suggested that the P. argus nutritional
      condition is a good estimator of the habitat condition. Besides, according to the
      applied K estimation methodology, it was found that different groups of lobsters
      that have resemblant nutritional condition, did not necessarily observe
      similarities in the overall mean length or weight, so they could exist under
      different habitat conditions.

PMID- 22458224
TI  - Diversity and distribution of aquatic insects in Southern Brazil wetlands:
      implications for biodiversity conservation in a Neotropical region.
AB  - The selection of priority areas is an enormous challenge for biodiversity
      conservation. Some biogeographic methods have been used to identify the priority
      areas to conservation, and panbiogeography is one of them. This study aimed at
      the utilization of panbiogeographic tools, to identify the distribution patterns
      of aquatic insect genera, in wetland systems of an extensive area in the
      Neotropical region (approximately 280 000km2), and to compare the distribution of
      the biogeographic units identified by the aquatic insects, with the conservation
      units of Southern Brazil. We analyzed the distribution pattern of 82 genera
      distributed in four orders of aquatic insects (Diptera, Odonata, Ephemeroptera
      and Trichoptera) in Southern Brazil wetlands. Therefore, 32 biogeographic nodes
      corresponded to the priority areas for conservation of the aquatic insect
      diversity. Among this total, 13 were located in the Atlantic Rainforest, 16 in
      the Pampa and three amongst both biomes. The distribution of nodes showed that
      only 15% of the dispersion centers of insects were inserted in conservation
      units. The four priority areas pointed by node cluster criterion must be
      considered in further inclusions of areas for biodiversity conservation in
      Southern Brazil wetlands, since such areas present species from different
      ancestral biota. The inclusion of such areas into the conservation units would be
      a strong way to conserve the aquatic biodiversity in this region.

PMID- 22458225
TI  - Longitudinal variation in the composition of the benthic macroinvertebrate fauna
      of a typical North coast Jamaican river.
AB  - Benthic macroinvertebrate fauna plays a major role in river ecosystems,
      especially those of tropical islands. Since there is no information on the
      distribution of benthic invertebrates along a Jamaican river, we report here on
      the composition of the benthic fauna of the Buff Bay river, on the Northern coast
      of Jamaica. A total of 14 samples were collected from five sites, using kick nets
      and a Surber sampler, between May 1997 and October 1998. We also examined the
      applicability of the rhithron/potamon model, and some of the premises of the
      River Continuum Concept (RCC) in relation to the distribution of invertebrate
      taxa. The results showed a total of 38 taxa of identified invertebrates. A group
      of dominant taxa, composed mainly of immature stages of insects, occurred at all
      sites. Two notable characteristics of the river were the absence of a true
      potamonic fauna and the low representation of the shredder functional feeding
      group in the community We conclude that, while there was minor variation in the
      composition of the benthic macroinvertebrate fauna among the sites, this was a
      response to local conditions within the river system. The characteristics of the
      community did not conform to either of the models.

PMID- 22458226
TI  - Trophic ecology of the freshwater prawn, Pseudopalaemon bouvieri (Decapoda:
      Palaemonidae) in Northeastern Argentina, with remarks on population structure.
AB  - Freshwater decapod crustaceans are important components of food webs in these
      environments, but little is known about the diet of species that live in tropical
      waters. We studied the feeding ecology of the prawn Pseudopalaemon bouvieri and
      its population structure in two different areas with six lagoons, with a
      different composition and abundance of aquatic macrophytes. At each site of
      macrophytes banks, 18 prawns sample was collected with a hand net (1mm mesh size)
      from 1m2. In the laboratory, prawns cephalothorax length was measured, sex
      determined, and a total of 208 stomachs were examined for food items. Our results
      showed that the population abundance varied between 10 ind/m2 and 1 411 ind/m2.
      The cephalothorax length ranged between 6mm and 21mm, and the male:female ratio
      varied between 0.3 and 1.0, with a higher proportion of ovigerous females (21%)
      in area one than area two. P. bouvieri is omnivorous, and its diet was
      principally based on algae, plant remains, Protozoa, Rotifera, Oligochaeta,
      Crustacea, Insecta, detritus and other items. The analysis of the stomach content
      did not reveal any significant difference in the diet between juveniles and
      adults, and males and females of both areas consumed a similar diet (Kruskal
      Wallis test p=0.8273). We concluded that the dietary items consumed by prawns and
      the niche breadth were similar between the two areas, although the proportion of
      items consumed varied between lagoons of both areas. The density of P. bouvieri
      was different between areas, but the size of cephalothorax (CL) was similar.

PMID- 22458227
TI  - [Terrestrial gastropods zoogeography in Southern Tamaulipas, Mexico].
AB  - Biogeography of Mexican terrestrial mollusks is poorly known, although many
      studies have described some of their biological aspects. This study aimed to
      contribute with new information on the distribution of terrestrial mollusks in
      this region of high altitudinal, topographic and climatic variations of Southern
      Tamaulipas State, Mexico. For this, terrestrial gastropods were surveyed from
      December 1990 to November 2006. A total of 525 samples were obtained from 121
      localities, characterized with different vegetation types. The primary
      zoogeographical feature was the presence of many endemic taxa, with 45 species or
      subspecies, representing the 43%, the highest value for Northeastern Mexico. In
      addition, a total of 24 species (23%), were of Neotropical and Neartic
      distributions, and 15 species or subspecies (14%) exhibited Neotropical
      distributions. Furthermore, the family Spiraxidae showed the largest number of
      endemic species, with 17 species and two subspecies, and had the largest number
      of endemic species (27) for Northeastern Mexico.

PMID- 22458228
TI  - Effect of ivermectin on the survival and fecundity of Euoniticellus intermedius
      (Coleoptera: Scarabaeidae).
AB  - The State of Veracruz in Mexico is one of the main cattle producers, and uses
      several veterinary products for disease and parasite control. For parasite
      control, ivermectin is one of the most frequently used substances. Nevertheless,
      even though previous research conducted in other countries has found that this
      product has negative effects on beneficial coprophagous fauna, no studies have
      described its effects on coprophagous insects at a local scale in Veracruz,
      Mexico. This study evaluated Euoniticellus intermedius survival, fecundity,
      fertility and preimaginal development under laboratory conditions when ivermectin
      was added to cattle dung at three different concentrations. The design included
      two controls (spiked dung), and the following product concentrations: 0.01, 1.0
      and 100ppm, which were homogenized with wet cattle dung. 20 female-male E.
      intermedius couples between five and 15 days old were used and kept at 27 degrees
      C, 70% RH, and 12h light for 10 days. The survival of all specimens, the
      fertility of 20 females and the gonadal maturity of 17 males were verified. The
      larval development in 162 pieces of brood-mass was examined, and a total of 974
      larvae developed and reached adulthood. The highest ivermectin concentration was
      toxic at 1.0ppm dose, the survival of adults was reduced to almost the half, and
      at 100ppm, total mortality was observed. The effects on specimen reproductive
      systems showed that the ovary was not affected, that the testicle size increased,
      and that the fecundity and weight of brood-masses were reduced. Pre-imaginal
      development increased 0.5 times at 0.01ppm concentration, and the width of the
      cephalic capsule in third instar larvae diminished. The prolonging of development
      time may cause a phase lag in the field activity cycle, this lag may reduce the
      number of E. intermedius individuals and the efficiency of the environmental
      services that they provide.

PMID- 22458229
TI  - [Taxonomic composition and zoogeographical aspects of deep sea fishes (90-540m)
      from the Gulf of California, Mexico].
AB  - The Gulf of California has a high variety of ecosystems that allow different
      services and the fishery resources play a prominent role in its ecology,
      evolution and economics. Fish coastal species have been previously reported for
      most coastal areas, especially those species that are subject to fishing,
      however, little is known on the species from deep sea zones, due to sampling
      difficulties. We studied the deep sea fishes collected with trawl nets during
      three research surveys in the Gulf of California, Mexico in 2004-2005. We provide
      a systematic checklist and some notes on biogeographical aspects. For this, 74
      fishing hauls were done, and a total of 9 898 fishes were captured, belonging to
      two classes, 15 orders, 35 families, 53 genera and 70 species. The best
      represented families in number of species were: Paralichthyidae (eight),
      Serranidae (six), and Scorpaenidae and Triglidae with five species each one. The
      typical families from deep waters were: Ophidiidae, Moridae, Lophiidae,
      Scorpaenidae, Triglidae, Paralichthydae, Pleuronectidae and Cynoglossidae. Size
      range varied from 13cm for the Splinose searobin (Bellator xenisma) to 234cm in
      the Pacific Cutlassfish (Trichiurus nitens). The biogeographical affinity showed
      that species with affinity to the East Tropical Pacific (ETP) dominated, followed
      by species from San Diego-Panamic, San Diego-Panamic-Peruvian-Chilean and
      Oregonian-Cortes provinces, respectively. A biogeographic overlap was found in
      the fauna, which reflects the Gulf of California's geographical position, with
      distribution limits of species from temperate, tropical and warm-temperature
      transition affinities, divisions that characterize the Gulf of California.
      Taxonomic status of fish with a focus on composition, location, characterization
      and zoogeography are fundamental to any subject of biodiversity and fisheries
      management actions.

PMID- 22458230
TI  - Acute toxicity and cholinesterase inhibition of the nematicide ethoprophos in
      larvae of gar Atractosteus tropicus (Semionotiformes: Lepisosteidae).
AB  - Biomarkers are a widely applied approach in environmental studies. Analyses of
      cholinesterase (ChE), glutathione S-transferase (GST) and lipid peroxidation
      (LPO) are biomarkers that can provide information regarding early effects of
      pollutants at different biochemical levels on an organism. The aim of this study
      was to evaluate the biomarker approach on a Costa Rican native and relevant
      species. For this, larvae of gar (Atractosteus tropicus) were exposed to the
      organophosphorus nematicide, ethoprophos. Acute (96hr) exposure was conducted
      with pesticide concentrations ranging from 0.1 microg/L to 1 500 microg/L. The
      96hr LC50 calculated was 859.7 microg/L. After exposure, three biomarkers (ChE,
      GST and LPO) were analyzed in fish that survived the acute test. The lowest
      observed effect concentration (LOEC) regarding ChE activity inhibition was 50
      microg/L. This concentration produced a significant inhibition (p<0.05) of the
      enzyme by 20%. The highest concentration tested without showing any effect on ChE
      activity and therefore considered as no observed effect concentration (NOEC) was
      10 microg/L. Ethoprophos concentration of 400 microg/L caused a ChE inhibition by
      79%. In this study, no significant variations (p>0.05) in GST activity and LPO
      were observed in A. tropicus larvae after exposure to ethoprophos.

PMID- 22458231
TI  - Embryonic and larval development of Eugerres mexicanus (Perciformes: Gerreidae)
      in Tenosique, Tabasco, Mexico.
AB  - Most studies on Eugerres mexicanus mainly consider biogeographic and systematic
      aspects and rarely address reproductive characteristics, which are useful for
      fishery population management plans. This study aimed at evaluating the ontogeny
      of E. mexicanus, based on 30 embryos and 30 larvae sampled by induced spawning of
      breeders, taken in February 2009 from the Usumacinta River in Tenosique, Tabasco,
      Mexico. All descriptions of the embryonic development were based on morphometric
      and meristic data and followed standard methods. Eggs, recovered at the gastrula
      stage, had an average diameter of 1.17mm (SD=0.08). The bud stage appeared during
      the first three hours of development, in which the posterior side was adhered to
      the vitellus; Kupffer's vesicle was visible. Yolk-sac larvae hatched 18 hours
      after fertilization, exhibiting a light brown color and an average total length
      of 2.94mm (SD=0.70); the preflexion stage was reached eight days after hatching,
      with a total average length of 4.67mm (SD=0.50) and a total notochord length of
      4.45mm (SD=0.50). The flexion stage was reached on the 16th day, with an average
      total length of 6.66mm (SD=1.53), while postflexion was reached on the 24th day,
      with 10.33mm (SD=1.45). The pre-juvenile stage was reached on the 33rd day, with
      a total length of 14.30mm (SD=0.93), showing IX spines and 10 rays and III spines
      and eight rays in the dorsal and anal fins, respectively. The juvenile stage was
      reached by the 45th day, with an average length of 28.16mm (SD=1.93) and average
      weight of 4.75g (SD=1.49). Prejuveniles showed an initial pigmentation with dark
      colored dots in the superior and inferior jaw and dispersed on the head, while
      juveniles presented the same pigmentation pattern, decreasing towards the margin
      of the caudal peduncle. In conclusion, the embryonic developmental stages of E.
      mexicanus were typical for the Gerreidae group. However, their morphometric
      characters were slightly different since the diameter and size of the drop of oil
      were bigger than those reported for marine species. In addition, regarding
      pigmentation, the yolk-sac larvae of E. mexicanus were olive and yellow on the
      margin of the notochord, which differs from those reported for other species.
      This is the first recorded report on the reproductive biology and early life
      development of this species.

PMID- 22458232
TI  - [Performance of recirculating aquaculture systems in the intensive farming of
      Pacu Piaractus mesopotamicus (Characiformes: Characidae)].
AB  - An alternative to intensify fish production, reducing the environmental impact
      and production costs are recirculating aquaculture systems (RAS). The performance
      of a RAS was evaluated, as fish growth and water quality conditions, in a culture
      of Piaractus mesopotamicus reared for ornamental purposes. Two commercial food
      brands with different protein contents (18%-T1 and 28%-T2), were given to
      juvenile fishes during an eight weeks period. Growth was measured bi-weekly:
      standard length (Lp), peak height (A), weight and multiple condition factor (KM).
      The evaluation of water parameters included: dissolved oxygen, NH3-NH4, pH, NO2,
      NO3, KH carbonate hardness and PO4. NH3-N rate production was analyzed following
      Timmons-Ebeling model. Results demonstrated significant differences in weight
      only, and T2 showed a 7.5% higher value than T1; nevertheless, treatment T1 had a
      higher KM. In general, water quality values were suitable for growth: OD=T1: 4.23
      +/- 1.23; T2: 4.13 +/- 0.86; NH3=T1: 0.02 +/- 0.02; T2: 0.06 +/- 0.10; however,
      pH was an exception (T1: 6.95 +/- 0.98; T2: 7.11 +/- 1.03), displaying lethal
      rates (<5) by the fifth week. Systems NH3 removal had a 99.4% to 100% efficiency.
      Final fish biomass was 22.03kg for T1 and 27.49kg for T2. We concluded that the
      systems were able to maintain suggested density up to the experimental fifth
      week. Water quality parameters remained in suitable levels, with the pH
      exception. Cultured fishes reached their commercial size (10cm) in eight weeks.

PMID- 22458233
TI  - [Reproductive biology of the golden snapper Lutjanus inermis (Perciformes:
      Lutjanidae) in the central Mexican Pacific].
AB  - Reproductive aspects and information on the effect of fishery activities over
      this species stock are scarce, despite the imperative need of effective
      protection and resource management programs. To support the possible
      establishment of closed seasons and catch levels for the area, our study aimed to
      evaluate the spawning season of the Golden snapper (Lutjanus inermis). For this,
      fish caught by artisanal fisheries in the Navidad, Tenacatita and Chamela bays
      (Jalisco, Mexico) were sampled monthly from 1999-2008, and analyzed sex ratios,
      spawning season and size at first maturity. A total of 311 (53.1%) females and
      275 (46.9%) males were caught, and the observed sex ratio was 1:0.88. The total
      length range was 14.4-37.0cm and total weight range from 48-575g. The length at
      first maturity was 23.9cm TL for females and 23.6cm TL for males. The
      gonadosomatic index showed two principal reproductive periods in the year
      (February-April and September-November), when the largest number of mature gonads
      were observed. Ovaries were of asynchronic development type and seven oocyte
      development stages were identified. Testicles showed lobular development and
      spermatozoa were observed in the center of the cysts and in the collecting ducts.
      It is important to mention that our results support the current suitable
      exploitation of this species in the area.

PMID- 22458234
TI  - [Seasonal changes in the dorsal coloration in the lizard Aspidoscelis costata
      costata (Squamata: Teiidae)].
AB  - Color and color patterns in animals are important characteristics that bring
      protection, by dampening the ability of predators that depend on their sight to
      detect their preys. In lizards, the dorsal coloration plays a key role in
      communication of intraspecific signals such as social cues. In this study, we
      evaluated the seasonal changes in the dorsal coloration of the wide foraging
      lizard A. costata costata, in Tonatico, State of Mexico, Mexico. The seasonal
      evaluation included: the rainy season from mid June to mid September (can also
      include the end of May to early October); and the dry season for the rest of the
      year. The dorsal coloration of A. costata costata and their microhabitats were
      evaluated by contrasting the color pattern with an identification guide and the
      control colors of Pantone, during 11 samplings carried out from February-October
      2007. Individual lizard analysis recorded snout-vent length, sex and stage
      (juveniles and adults). Besides, all animals were marked by toe-clipping,
      allowing to distinguish dorsal coloration between seasons, sex and stage. A total
      of 95 lizards were analyzed (53 and 42 for the dry and rainy seasons
      respectively). We found that the dorsal coloration in A. costata costata varies
      seasonally and with microhabitats: during the dry season individuals show a brown
      coloration whereas during the rainy season becomes greener, as the background
      dominant vegetation color. The results of the present study suggest that: 1) the
      variation in dorsal coloration in A. costata costata plays an important role in
      the survival (by cryptic camouflage) of this widely foraging species; 2) the
      changes in the dorsal coloration of A. costata costata are individually expressed
      traits, since the coloration of the same lizard is either brown or green
      depending on the season; and 3) the cryptic functions of the dorsal coloration in
      widely foraging species have been largely underestimated. We discuss the possible
      influence of the changes in coloration in an habitat that changes drastically
      between both dry and rainy seasons.

PMID- 22458235
TI  - Habitat use, size structure and sex ratio of the spot-legged turtle, Rhinoclemmys
      punctularia punctularia (Testudines: Geoemydidae), in Algodoal-Maiandeua Island,
      Para, Brazil.
AB  - Rhinoclemmys punctularia punctularia is a semi-aquatic chelonian found in
      Northern South America. We analyzed the habitat use, size structure and sex ratio
      of the species on Algodoal-Maiandeua Island, a protected area on the Northeastern
      coast of the Brazilian state of Para. Four distinct habitats (coastal plain lake,
      flooded forest "igapo", interdunal lakes, and tidal channels) were surveyed
      during the rainy (March and April) and dry (August and September) seasons of
      2009, using hoop traps. For the analysis of population structure, additional data
      were taken in March and August, 2008. A total of 169 individuals were captured in
      flooded forest (igapo), lakes of the coastal plain and, occasionally, in
      temporary pools. Capture rates were highest in the coastal plain lake, possibly
      due to the greater availability of the fruits that form part of the diet of R. p.
      punctularia. Of the physical-chemical variables measured, salinity appeared to be
      the only factor to have a significant negative effect on capture rates. The sex
      ratio was only slightly biased to females, and did not vary between habitats or
      seasons. Straight carapace length was significantly larger in females, but did
      not vary between habitats. Overall, the evidence indicates that both biotic and
      abiotic factors like food availability, low current and salinity, influence the
      habitats selection and use by R. p. punctularia on Algodoal-Maiandeua Island.

PMID- 22458236
TI  - [Genetic variability in captive populations of Crocodylus moreletii (Crocodylia:
      Crocodylidae) using microsatellites markers].
AB  - Crocodylus moreletii, an extinction threatened species, represents an emblem for
      tropical ecosystems in Mexico. Surprisingly, there is a lack of information about
      their genetic constitution, which should be evaluated for a proper management ex
      situ and for making decisions on the release of crocodiles into natural habitats.
      The aim of this study was to characterize and compare the genetic variability of
      four populations of C. moreletii (two wild versus two born ex situ). Through PCR
      were amplified seven microsatellite polymorphic loci, however a heterozygote
      deficit, diminished by the presence of null alleles, was found in the populations
      (average Ho=0.02). The AMOVA indicated that the highest proportion of genetic
      variability is within populations, and a limited genetic differentiation among
      populations (average F(ST)=0.03), probably due to high inbreeding index (average
      F(IS)=0.97). When comparing the genetic variability between and within other
      crocodilian species, we found that in C. moreletii is well below those reported.
      We concluded that the limited genetic variability in ex situ born populations is
      probably due to a founder effect derived from the social structure of their
      progenitors, and by the bottleneck effect, inferred by the limited effective
      population size, that historically characterizes their natural distribution in
      wild populations.

PMID- 22458237
TI  - Ovarian folliculogenesis in collared peccary, Pecari tajacu (Artiodactyla:
      Tayassuidae).
AB  - The sustainability and production of collared peccary (Pecari tajacu) has been
      studied in the last few years; however, further information on its reproduction
      is necessary for breeding systems success. Understanding folliculogenesis aspects
      will contribute to effective reproductive biotechniques, which are useful in the
      preservation and production of wildlife. The aim of this study was-to evaluate
      the ovarian folliculogenesis in collared peccary. Ovaries from six adult females
      of collared peccary were obtained through ovariectomy and analyzed. These were
      fixed in aqueous Bouin's solution and sectioned into 7 microm slices, stained
      with hematoxilin-eosin and analyzed by light microscopy. The number of pre-antral
      and antral follicles per ovary was estimated using the Fractionator Method. The
      follicles, oocytes and oocyte nuclei were measured using an ocular micrometer.
      Results showed that the length, width, thickness, weight, and the gross anatomy
      of the right and left ovaries were not significantly different. However, the mean
      number of corpora lutea was different between the phases of the estrous cycle
      (p<0.05), with the highest mean in the luteal phase. Primordial follicles were
      found in the cortex; the oocytes were enveloped by a single layer of flattened
      follicular cells. In the primary follicles, proliferation of the follicular cells
      gave rise to cuboidal cells (granulosa cells). The secondary follicle was
      characterized by two or more concentric layers of cuboidal cells (granulosa),
      beginning of antrum formation, and the presence of pellucid zone and theca cells.
      Antral follicles were characterized by a central cavity (antrum), the presence of
      cumulus oophorus and theca layers (interna and externa). In the right ovary, the
      values of the primordial and primary follicles were similar, but significantly
      different from the secondary ones (p<0.05). In the left ovary, significant
      differences were observed between all follicles in the follicular phase (p<0.05);
      the mean number of primordial and primary follicles was similar in the luteal
      phase. The mean number of pre-antral follicles and antral follicles in the
      follicular phase was higher in the left ovary (p<0.05). The mean number of antral
      follicles in the luteal phase was similar in both ovaries. We also found
      significant differences in mean diameter of preantral follicles, oocyte,
      granulosa layer and oocyte nucleus during the estrous cycle. In the antral
      follicles a significant difference was observed only in follicular diameter
      (p<0.05). The predominance of active primordial and primary follicles was found
      in both phases; otherwise the secondary follicles and antral follicles showed a
      high degree of degeneration. The results obtained in the present work will
      strengthen the development of biotechnology programs to improve the productive
      potential and conservation of the collared peccary.

PMID- 22458238
TI  - [Odocoileus virginianus diet (Artiodactyla: Cervidae) in a temperate forest of
      Northern Oaxaca, Mexico].
AB  - The Sierra Madre de Oaxaca region, located in the Northern state of Oaxaca,
      Mexico, is an area of forest ecosystems subject to high exploitation rates,
      although in some areas its temperate forests are conserved by indigenous
      community initiatives that live there. We analyzed the diet of white tailed-deer
      (Odocoileus virginianus) in the localities of Santa Catarina Lachatao and San
      Miguel Amatlan from June 1998 to August 1999. Sampling was done during both the
      wet and dry seasons, and included the observation of browsing traces (238
      observations), microhistological analysis of deer feces (28 deer pellet-groups),
      and two stomach content analysis. The annual diet of white-tailed deer was
      composed of 42 species from 23 botanical families. The most represented families
      in the diet of this deer were Fagaceae, Asteraceae, Ericaceae and Fabaceae. There
      were significant differences in the alpha diversity of the diet during the wet
      and dry seasons (H'=2.957 and H'=1.832, respectively). The similarity percentage
      between seasons was 56%. Differences in plant species frequency were
      significantly higher during the wet season. Herbaceous plants made up the
      greatest percentage of all the species consumed. The preferred species throughout
      the year were Senecio sp. (shrub), Sedum dendroideum (herbaceous), Arctostaphylos
      pungens (shrub) and Satureja macrostema (shrub). Diet species richness was found
      to be lower than that observed in a tropical forest (Venezuela), tropical dry
      forest (Mexico) and temperate deciduous and mixed forest (Mexico), but similar to
      the diet species richness observed in a tropical dry forest (Costa Rica) and
      temperate coniferous and deciduous forests (USA).

PMID- 22458239
TI  - Preliminary inventory of mammals from Yurubi National Park, Yaracuy, Venezuela
      with some comments on their natural history.
AB  - In Venezuela, mammals represent an important group of wildlife with high
      anthropogenic pressures that threaten their permanence. Focused on the need to
      generate baseline information that allows us to contribute to document and
      conserve the richness of local wildlife, we conducted a mammalogical inventory in
      Yurubi National Park, located in Yaracuy State in Venezuela. We carried out
      fieldworks in three selected vegetation types: an evergreen forest at 197m, a
      semi-deciduous forest ranging between 100-230m, and a cloud forest at 1 446m. We
      used Victor, Sherman, Havahart and pitfall traps for the capture of small non
      volant mammals and mist nets for bats. In addition, we carried out interviews
      with local residents and direct-indirect observations for medium-large sized
      mammals. At least 79 species inhabit the area, representing 28% of the species
      recorded for the North side of the country. Chiroptera (39 spp.), Carnivora (13
      spp.) and Rodentia (9 spp.) were the orders with the highest richness, as
      expected for the Neotropics. The evergreen forest had the greatest species
      richness (n=68), with a sampling effort of 128 net-hours, 32 bucket-days, 16
      hours of observations, and three persons interviewed, followed by cloud forest
      (n=45) with 324 net-hours, 790 traps-night, 77 bucket-days, 10 hours of
      observations, and one person interviewed. The lowest richness value was in the
      semi-deciduous forest (n=41), with 591 traps-night, 15 net-hours, 10 hours of
      observations and three persons interviewed. Data and observations obtained in
      this inventory (e.g., endemism, species known as "surrogate species" threatened
      in Venezuela) give an important role at the Yurubi National Park in the
      maintenance and conservation of local ecosystems and wildlife, threatened by
      human pressures in the Cordillera de la Costa.

PMID- 22458240
TI  - A method for seedling recovery in Jatropha curcas after cryogenic exposure of the
      seeds.
AB  - Actually, the germplasm of Jatropha spp. is conserved as whole plants in field
      collections. Under this storage method, the genetic resources are exposed to
      disease, pest and natural hazards such as human error, drought and weather
      damage. Besides, field genebanks are costly to maintain and with important
      requirements of trained personnel. Thus, the development of efficient techniques
      to ensure its safe conservation and regeneration is therefore of paramount
      importance. In this work we describe a method for Jatropha curcas seeds
      cryoexposure and seedling recovery after thawed. In a first experiment, an
      efficient protocol for in vitro plant recovery was carried out using zygotic
      embryo or seeds with or without coat. In a second experiment, desiccated seeds
      with or without coat were exposed to liquid nitrogen and evaluated after
      cryoexposure. Germination percentages were variable among treatments, and seeds
      demonstrated tolerance to liquid nitrogen exposure under certain conditions.
      Seeds of J. curcas presented up to 99.6% germination after seed coat removal.
      Seeds with coat cultured in vitro did not germinate, and were 60% contaminated.
      The germination of the zygotic embryos was significantly higher in the 1/2 MS
      medium (93.1%) than in WPM medium (76.2%), but from zygotic embryo, abnormal
      seedlings reached up to 99%. Seeds with coat exposed to liquid nitrogen showed
      60% germination in culture after coat removal with good plant growth, and seeds
      cryopreserved without coat presented 82% germination, but seedlings showed a
      reduced vigor and a significant increase in abnormal plants. Seeds cultured in
      vitro with coat did not germinate, independently of cryoexposure or not. This
      study reports the first successful in vitro seedling recovery methodology for
      Jatropha curcas seeds, after a cryopreservation treatment, and is recommended as
      an efficient procedure for in vitro plant recovery, when seeds are conserved in
      germplasm banks by low or cryotemperatures.

PMID- 22458241
TI  - Growth rate and ring width variability of teak, Tectona grandis (Verbenaceae) in
      an unmanaged forest in East Timor.
AB  - Teak (Tectona grandis) is one of the most valuable timbers in international trade
      and an important species for tropical forestry. Teak is found on the island of
      East Timor but no information is available on teak growth from this region. A
      pure stand planted in 1940-50 in the North of East Timor and left unmanaged was
      studied. Fifteen trees were sampled in October-November 2003 and stem discs taken
      at three height levels of its height (1.7m, 9.5m and 18.7m), and cores were
      collected at DBH. Transverse surfaces of the discs and cores were polished for
      ring identification. Core cross sections were first digitized and disc cross
      sections were observed under the microscope. Three randomly selected radii were
      analyzed in each disc. Ring width measurement and ring counting were done using
      image analysis software. The distinction between heartwood and sapwood was
      performed macroscopically by colour difference, and heartwood radius and sapwood
      width were measured. The relationship between stem and heartwood radius was
      studied for each disc and heartwood percentage by radius was determined. Radial
      ring width curves are presented for the different axial positions within the
      stem, and ring width variability was analyzed. Growth rates were calculated and
      age-radius relationships were estimated using cumulative growth curves. Growth
      rings were large and well defined in the juvenile phase, reflecting the specie's
      fast-growing character. The year-to-year variation of ring width showed a similar
      pattern among trees. Mean ring width ranged between 4.3-7.3mm for the first 20
      years and 3.3-5.1mm for 30 to 45 years. Pith eccentricity was evident in the
      lower part of the stem and ring wedging occurred. On average, heartwood
      represented 84% of the radius and sapwood contained 6 to 11 rings. The age
      related variation of ring width and the occurrence in the lower part of the tree
      stems of eccentricity and wedging rings, highlights the importance of appropriate
      stand management, particularly regarding basal density distribution over time,
      whenever optimized timber production is envisaged.

PMID- 22458242
TI  - Germination and seedling morphology of four South American Smilax (Smilacaceae).
AB  - Species of Smilax, also known as greenbrier, are widely distributed in Brazil and
      their commercial trades are carried out by the extractivism of native species. We
      the aim to provide information about the germination and development of seedlings
      in four Smilax species, different experiments were developed under controlled
      conditions. We evaluated two germination treatments: temperature (30 degrees C
      and 20-30 degrees C) and light (presence/ absence), and for few cases the
      tetrazolium treatment was applied. A different treatment response was observed
      among the studied species. Light had a significant influence in S. brasiliensis,
      with the highest germination rates at 20-30 degrees C in dark conditions. S.
      campestris showed significant differences among temperature treatments, but not
      to light; while S. cissoides showed high germination rates (66-78%),
      independently of treatment. However, S. polyantha had low germination rates (19
      24%). After one year, the expanded leaves showed different characteristics among
      the studied species. Leaves of S. brasiliensis were ovate, coriaceous, three main
      veins and prickle-like structures only on the midrib on abaxial face. S.
      campestris leaves were oblong, coriaceous and prickle-like structures were
      located at the leaf midrib and margin. S. cissoides had ovate-elliptic,
      membranaceous leaves, with three main veins with prickle-like structures on the
      abaxial face. S. polyantha leaves showed ovate-elliptic, coriaceous leaves, with
      three main veins, translucent secondary veins and no prickle-like structures. A
      seedling identification key was elaborated based on morphological
      characteristics.

PMID- 22458243
TI  - Glandular trichomes in Connarus suberosus (Connaraceae): distribution, structural
      organization and probable functions.
AB  - Connarus suberosus is a typical species of the Brazilian Cerrado biome, and its
      inflorescences and young vegetative branches are densely covered by dendritic
      trichomes. The objective of this study was to report the occurrence of a
      previously undescribed glandular trichome of this species. The localization,
      origin and structure of these trichomes were investigated under light,
      transmission and scanning electron microscopy. Collections were made throughout
      the year, from five adult specimens of Connarus suberosus near Botucatu, Sao
      Paulo, Brazil, including vegetative and reproductive apices, leaves and fruits in
      different developmental stages, as well as floral buds and flowers at anthesis.
      Glandular trichomes (GTs) occurred on vegetative and reproductive organs during
      their juvenile stages. The GTs consisted of a uniseriate, multicellular peduncle,
      whose cells contain phenolic compounds, as well as a multicellular glandular
      portion that accumulates lipids. The glandular cell has thin wall, dense
      cytoplasm (with many mitochondria, plastids and dictyosomes), and a large nucleus
      with a visible nucleolus. The starch present in the plastids was hydrolyzed
      during the synthesis phase, reducing the density of the plastid stroma. Some
      plastids were fused to vacuoles, and some evidence suggested the conversion of
      plastids into vacuoles. During the final activity stages of the GTs, a darkening
      of the protoplasm was observed in some of the glandular cells, as a programmed
      cell death; afterwards, became caducous. The GTs in C. suberosus had a temporal
      restriction, being limited to the juvenile phase of the organs. Their presence on
      the exposed surfaces of developing organs and the chemical nature of the reserve
      products, suggest that these structures are food bodies. Field observations and
      detailed studies of plant-environment interactions, as well as chemical analysis
      of the reserve compounds, are still necessary to confirm the role of these GTs as
      feeding rewards.

PMID- 22458244
TI  - The case management process in effective and efficient action.

PMID- 22458245
TI  - Performing the necessary assessments.

PMID- 22458246
TI  - Lupus tumidus following the lines of Blaschko.

PMID- 22458247
TI  - A multicenter, randomized controlled trial of immediate total-body CT scanning in
      trauma patients (REACT-2).
AB  - BACKGROUND: Computed tomography (CT) scanning has become essential in the early
      diagnostic phase of trauma care because of its high diagnostic accuracy. The
      introduction of multi-slice CT scanners and infrastructural improvements made
      total-body CT scanning technically feasible and its usage is currently becoming
      common practice in several trauma centers. However, literature provides limited
      evidence whether immediate total-body CT leads to better clinical outcome then
      conventional radiographic imaging supplemented with selective CT scanning in
      trauma patients. The aim of the REACT-2 trial is to determine the value of
      immediate total-body CT scanning in trauma patients. METHODS/DESIGN: The REACT-2
      trial is an international, multicenter randomized clinical trial. All
      participating trauma centers have a multi-slice CT scanner located in the trauma
      room or at the Emergency Department (ED). All adult, non-pregnant, severely
      injured trauma patients according to predefined criteria will be included.
      Patients in whom direct scanning will hamper necessary cardiopulmonary
      resuscitation or who require an immediate operation because of imminent death
      (both as judged by the trauma team leader) are excluded. Randomization will be
      computer assisted. The intervention group will receive a contrast-enhanced total
      body CT scan (head to pelvis) during the primary survey. The control group will
      be evaluated according to local conventional trauma imaging protocols (based on
      ATLS guidelines) supplemented with selective CT scanning. Primary outcome will be
      in-hospital mortality. Secondary outcomes are differences in mortality and
      morbidity during the first year post trauma, several trauma work-up time
      intervals, radiation exposure, general health and quality of life at 6 and 12
      months post trauma and cost-effectiveness. DISCUSSION: The REACT-2 trial is a
      multicenter randomized clinical trial that will provide evidence on the value of
      immediate total-body CT scanning during the primary survey of severely injured
      trauma patients. If immediate total-body CT scanning is found to be the best
      imaging strategy in severely injured trauma patients it could replace
      conventional imaging supplemented with CT in this specific group. TRIAL
      REGISTRATION: ClinicalTrials.gov: (NCT01523626).

PMID- 22458248
TI  - Possible cross-infection of Dichelobacter nodosus between co-grazing sheep and
      cattle.
AB  - BACKGROUND: The aim of this study was to investigate possible cross-infection of
      Dichelobacter nodosus in Norwegian farms practising co-grazing of sheep and
      cattle. METHODS: Thirteen farms practising co-grazing of sheep and cattle were
      included in this descriptive study: five farms with a history of severe ovine
      footrot (Group I) and eight farms with free-stall housing of cattle and signs of
      mild or no footrot in sheep (Group II). Sampling for PCR detection of D. nodosus
      was performed from animals in all farms, and clinical claw examination of sheep
      and cattle was performed in Group II. D. nodosus positive samples were analysed
      by a multiplex PCR method that detects variants of the fimA gene corresponding to
      D. nodosus serogroups A through I. RESULTS: D. nodosus serogroup A was identified
      more frequently in sheep from farms with a history of severe footrot (Group I)
      versus from Group II, and in most of the farms with a history of severe footrot
      there was a coexistence of D. nodosus serogroup A in sheep and cattle. In one
      farm heel horn erosion and dermatitis emerged in cattle after co-grazing with
      sheep suffering from severe footrot where D. nodosus serogroup A was detected.
      Six months later heel horn erosion and dermatitis were still diagnosed, and D.
      nodosus serogroup A was identified. Out of the 16 D. nodosus positive sheep
      samples from Group II, ten of the samples were positive by the fimA serogrouping
      PCR. Among these 10 samples all serogroups except G were detected. All the D.
      nodosus serogroups detected in sheep were also present in the corresponding
      cattle herds. CONCLUSION: The clinical findings and the coexistence of the same
      serogroups in co-grazing sheep and cattle could indicate cross-infection.
      However, further research including isolation of the bacterial strains, virulence
      testing and genetic identification, is needed.

PMID- 22458249
TI  - Responses of potential users to the intracortical visual prosthesis: final themes
      from the analysis of focus group data.
AB  - Although visual implant prosthesis projects are advancing, little exists in the
      literature on the factors that would lead an individual to volunteer for such an
      experimental procedure. Many ethical issues are raised in recruiting and
      involving individuals in experimental implant procedures, most involving autonomy
      and informed consent. This report provides perspectives of 30 totally or legally
      blind older individuals on their expectations about a potential visual implant,
      their motivations for volunteering, and the processes they would use for decision
      making. Data were collected in eight focus groups, using semistructured focus
      group processes. Among the primary reasons a person with seriously impaired
      vision would volunteer for a new implant procedure are helping others, exploring
      the unknown, and restoring perception. The decision to participate in an
      experimental brain implant procedure is complex. Potential recipients have many
      questions about the device and the procedure, the perceived risks, and the
      commitment of a research team to the participants once a device has been
      implanted. Some would involve their family in a decision; others are more
      comfortable making the decision independent, after consulting others. The themes
      identified provide a guide for recruiting and ensuring an ethical experience for
      participants in experimental protocols.

PMID- 22458251
TI  - Experimental murine model of disseminated infection by Saksenaea vasiformis:
      successful treatment with posaconazole.
AB  - We have determined the in vitro activity of amphotericin B (AMB) and posaconazole
      (PSC) against Saksenaea vasiformis using broth microdilution and disk diffusion
      methods and determined the minimal fungicidal concentration (MFC). PSC was found
      to have the greatest in vitro activity in all cases and was the most efficacious
      in prolonging survival and reducing the fungal load in an immunocompetent murine
      model of disseminated infection caused by four strains of the fungus.

PMID- 22458250
TI  - Trypanosoma cruzi antioxidant enzymes as virulence factors in Chagas disease.
AB  - SIGNIFICANCE: Chagas disease (CD) affects several million people in Latin America
      and is spreading beyond its classical boundaries due to the migration of infected
      host and insect vectors, HIV co-infection, and blood transfusion. The current
      therapy is not adequate for treatment of the chronic phase of CD, and new drugs
      are warranted. RECENT ADVANCES: Trypanosoma cruzi is equipped with a specialized
      and complex network of antioxidant enzymes that are located at different
      subcellular compartments which defend the parasite against host oxidative
      assaults. Recently, strong evidence has emerged which indicates that enzyme
      components of the T. cruzi antioxidant network (cytosolic and mitochondrial
      peroxiredoxins and trypanothione synthetase) in naturally occurring strains act
      as a virulence factor for CD. This precept is recapitulated with the observed
      increased resistance of T. cruzi peroxirredoxins overexpressers to in vivo or in
      vitro nitroxidative stress conditions. In addition, the modulation of
      mitochondrial superoxide radical levels by iron superoxide dismutase (FeSODA)
      influences parasite programmed cell death, underscoring the role of this enzyme
      in parasite survival. CRITICAL ISSUES: The unraveling of the biological
      significance of FeSODs in T. cruzi programmed cell death in the context of
      chronic infection in CD is still under examination. FUTURE DIRECTIONS: The role
      of the antioxidant enzymes in the pathogenesis of CD, including parasite
      virulence and persistence, and their feasibility as pharmacological targets
      justifies further investigation.

PMID- 22458252
TI  - Rare and new etiological agents revealed among 178 clinical Aspergillus strains
      obtained from Czech patients and characterized by molecular sequencing.
AB  - A collection of 178 Aspergillus isolates, recovered from Czech patients, mostly
      from 2007-2011, was subjected to multilocus DNA sequence typing using the ITS
      region, beta-tubulin, and calmodulin genes. An unusually wide spectrum of
      etiologic agents that included 36 species of Aspergillus is discussed in the
      context of recent taxonomic and clinical reports. Invasive aspergillosis (IA),
      onychomycosis, and otitis externa were the predominant clinical entities. Five
      cases due to species newly proven as etiologic agents of human mycoses, as well
      as cases with unique clinical manifestations caused by unusual agents are
      discussed in more detail. Three species (i.e., A. insulicola, A. westerdijkiae
      and A. tritici) were identified as the confirmed etiologic agents of non
      dermatophytic onychomycosis. Emericella rugulosa was recovered from a premature
      newborn with a fatal necrotising disseminated infection and is reported for only
      the second time as the cause of IA. Furthermore, we document the first infection
      due to A. calidoustus in a patient with chronic granulomatous disease. The
      infection manifested as a latent brain aspergilloma with an unusual clinical
      laboratory finding. In addition to the well-known agents of human mycosis,
      several rarely isolated or poorly documented species were identified. An
      undescribed cryptic species related to A. versicolor was found to be common among
      isolates linked to proven and probable onychomycosis. An isolate representing A.
      fresenii, or an unnamed sister species, were causal agents of otomycosis. Three
      well defined, and tentative new species belonging to section Cervini, Candidi and
      Aspergillus (Eurotium spp.), were associated with cases of probable
      onychomycosis.

PMID- 22458253
TI  - Additional insights into luminescence process of polycyclic aromatic hydrocarbons
      with carbonyl groups: photophysical properties of secondary N-alkyl and tertiary
      n,n-dialkyl carboxamides of naphthalene, anthracene, and pyrene.
AB  - Here we report the substitution effects of N-alkyl and N,N-dialkyl carboxamide
      groups on the fluorescence properties of polycyclic aromatic hydrocarbon
      chromophores, so as to control their fluorescence properties. The fluorescence
      properties of compounds obtained using solvents with different polarities showed
      very little change, indicating that the modified compounds do not form charge
      transfer states. TD-DFT calculations and measurements performed at low
      temperature (78 K) and in viscous solvents revealed that the N-alkyl and N,N
      dialkyl carboxamide groups tend to reduce the contributions from intersystem
      crossing and increase those from internal conversion. Considering that the
      fluorescence mechanism of low-fluorescence carbonyl compounds such as aldehyde
      and ketone is dominated by intersystem crossing and that of high-luminescence
      carbonyl compounds such as carboxylic acid and ester is dominated by a radiative
      process, it can be said that the photophysical process of N-alkyl and N,N-dialkyl
      carboxamides is novel. In addition, the calculation results for excited states
      indicated that such contributions can be controlled by selecting the appropriate
      polycyclic aromatic hydrocarbon or amide structure, in addition to solvent
      viscosity and temperature.

PMID- 22458254
TI  - Database on radiogenic cancer in animals.

PMID- 22458255
TI  - Database of radiogenic cancer in experimental animals exposed to low doses of
      ionizing radiation.
AB  - For decades, there have been debates regarding the nature of the relationship
      between exposure to low doses of ionizing radiation and cancer risk. Under the
      linear no-threshold hypothesis, which serves as a theoretical basis for current
      radiation protection standards, the risk of cancer at low levels of exposure is
      presumed to be directly proportional to dose. Opponents of this hypothesis claim
      that there are threshold doses for radiation carcinogenesis, or even a reduction
      in cancer risk at low doses (a phenomenon referred to as "radiation hormesis").
      Epidemiological, animal, molecular, and cellular studies were conducted to
      resolve this controversy, although each of these study types has its strengths
      and limitations. Although the results of animal experiments are not directly
      applicable to humans, data can substantially add to our knowledge on the form of
      relationship between radiation dose and cancer risk in a wide range of doses.
      Laboratory animals are a homogeneous population with little biological
      variability; animal experiments are conducted under controlled conditions with
      good estimates of radiation doses. In order to address the question of whether or
      not the dose-response curve for radiation carcinogens is linear at low doses, a
      comprehensive database of animal carcinogenesis experiments was assembled
      involving exposure to different types of ionizing gradation. The database
      includes virtually all publicly accessible data on the induction of radiogenic
      cancer in laboratory mammals. This review provides a descriptive overview of the
      experiments included in the database, along with a qualitative assessment of the
      shape of the dose-response relationship for radiation carcinogenesis at low doses
      in experimental animals.

PMID- 22458256
TI  - A meta-analysis of evidence for hormesis in animal radiation carcinogenesis,
      including a discussion of potential pitfalls in statistical analyses to detect
      hormesis.
AB  - A database containing 800 datasets on the incidence of specific tumor types from
      262 radiation carcinogenicity experiments identified in a comprehensive
      literature search through September 2000 was analyzed for evidence of hormesis.
      This database includes lifetime studies of tumorigenic responses in mice, rats,
      and dogs to exposures to alpha, beta, gamma, neutron, or x-ray radiation. A J
      shaped dose response, in the form of a significant decreased response at some low
      dose followed by a significant increased response at a higher dose, was found in
      only four datasets from three experiments. Three of these datasets involved the
      same control animals and two also shared dosed animals; the J shape in the fourth
      dataset appeared to be the result of an outlier within an otherwise monotonic
      dose response. A meta-analysis was conducted to determine whether there was an
      excess of dose groups with decreases in tumor response below that in controls at
      doses below no-observed-effect levels (NOELs) in individual datasets. Because the
      probability of a decreased response is generally not equal to the probability of
      an increased response even in the null case, the meta-analysis focused on
      comparing the number of statistically significant diminished responses to the
      number expected, assuming no dose effect below the NOEL. Only 54 dose groups out
      of the total of 2579 in the database had doses below the dataset-specific NOEL
      and that satisfied an a priori criterion for sufficient power to detect a reduced
      response. Among these 54, a liberal criterion for defining a significant
      decreases identified 15 such decreases, versus 54 * 0.2 = 10.8 expected. The
      excess in significant reductions was accounted for almost entirely by the excess
      from neutron experiments (10 observed, 6.2 expected). Nine of these 10 dose
      groups involved only 2 distinct control groups, and 2 pairs from the 10 even
      shared dosed animals. Given this high degree of overlap, this small excess did
      not appear remarkable, although the overlap prevented a formal statistical
      analysis. A comprehensive post hoc evaluation using a range of NOEL definitions
      and alternative ways of restricting the data entering the analysis did not
      produce materially different results. A second meta-analysis found that, in every
      possible low dose range ([0, d] for every dose, d) of each of the radiation
      types, the number of dose groups with significantly increased tumorigenic
      responses was either close to or exceeded the number showing significantly
      reduced responses. This meta-analysis was considered to be the more definitive
      one. Not only did it take dose into account by looking for consistent evidence of
      hormesis throughout defined low-dose ranges, it was also potentially less
      susceptible to limitations in experimental protocols that would cause individual
      animals to respond in a non-independent fashion. Overall, this study found little
      evidence in a comprehensive animal radiation database to support the hormesis
      hypothesis. However, the ability of the database to detect a hormetic effect was
      limited both by the small number of dose groups with doses below the range where
      positive effects have been found in epidemiological studies (<= 0.1 Gy) and by
      the limited power of many of these dose groups for detecting a decrease in
      response.

PMID- 22458259
TI  - Synthesis, crystal structure, and optical properties of a three-dimensional
      quaternary Hg-In-S-Cl chalcohalide: Hg7InS6Cl5.
AB  - A crystalline three-dimensional (3D) quaternary chalcohalide, Hg(7)InS(6)Cl(5)
      (1), has been synthesized through a solid-state reaction under medium
      temperature. It is the first example in the family of the Hg-IIIA-Q-X (Q = S, Se,
      Te; X = F, Cl, Br, I) systems. Compound 1 features a 3D network and has an
      optical band gap of 2.54 eV.

PMID- 22458257
TI  - Higher medical morbidity burden is associated with external locus of control.
AB  - OBJECTIVES: To describe the association between an increasing number of
      coexisting conditions and locus of control (LOC), a psychological construct
      reflecting the degree to which one perceives circumstances to be controlled by
      personal actions (internal LOC) versus outside factors (external LOC) in older
      adults. DESIGN: Cross-sectional study using survey data from the North Carolina
      Established Population for Epidemiologic Studies of the Elderly (NC EPESE) data
      set. SETTING: Community. PARTICIPANTS: Three thousand two hundred twelve
      community-dwelling adults aged 68 and older. MEASUREMENTS: Nine common medical
      conditions were assessed according to self-report. LOC was measured using a
      standard questionnaire. Analyses were adjusted for demographics, functional
      status (self-reported activities of daily living), cognition (Short Portable
      Mental Status Questionnaire), and depression score (Center for Epidemiologic
      Studies Depression Scale). RESULTS: A higher number of chronic conditions was
      associated with external LOC (beta = 0.37, P < .001). This relationship persisted
      after adjustment for age, race, sex, functional status, cognition, and depression
      (beta = 0.17, P < .001). Most individual conditions were not associated with LOC,
      although vision impairment (P < .001) and arthritis (P = .02) were associated
      with more-internal LOC. CONCLUSION: These results suggest that medically complex
      patients tend to exhibit a more-external LOC, meaning that they perceive little
      personal control over circumstances and environment. Clinicians should be aware
      of this tendency, because external LOC may impede an older adult's willingness to
      engage in the considerable task of managing multiple chronic conditions.

PMID- 22458258
TI  - On-chip synthesis of RNA aptamer microarrays for multiplexed protein biosensing
      with SPR imaging measurements.
AB  - Microarrays of RNA aptamers are fabricated in a one-step, multiplexed enzymatic
      synthesis on gold thin films in a microfluidic format and then employed in the
      detection of protein biomarkers with surface plasmon resonance imaging (SPRI)
      measurements. Single-stranded RNA (ssRNA) oligonucleotides are transcribed on
      chip from double-stranded DNA (dsDNA) templates attached to microarray elements
      (denoted as generator elements) by the surface transcription reaction of T7 RNA
      polymerase. As they are synthesized, the ssRNA oligonucleotides diffuse in the
      microfluidic channel and are quickly captured by hybridization adsorption onto
      adjacent single-stranded DNA (ssDNA) microarray elements (denoted as detector
      elements) that contain a sequence complementary to 5'-end of the ssRNA. The RNA
      aptamers attached to these detector elements are subsequently used in SPRI
      measurements for the bioaffinity detection of protein biomarkers. The
      microfluidic generator-detector element format permits the simultaneous
      fabrication of multiple ssRNA oligonucleotides with different capture sequences
      that can hybridize simultaneously to distinct detector elements and thus create a
      multiplexed aptamer microarray. In an initial set of demonstration experiments,
      SPRI measurements are used to monitor the bioaffinity adsorption of human
      thrombin (hTh) and vascular endothelial growth factor (VEGF) proteins onto RNA
      aptamer microarrays fabricated in situ with this on-chip RNA polymerase synthesis
      methodology. Additional SPRI measurements of the hydrolysis and desorption of the
      surface-bound ssRNA aptamers with a surface RNase H are used to verify the
      capture of ssRNA with RNA-DNA surface hybridization onto the detector elements.
      The on-chip RNA synthesis described here is an elegant, one-step multiplexed
      methodology for the rapid and contamination-free fabrication of RNA aptamer
      microarrays for protein biosensing with SPRI.

PMID- 22458260
TI  - Value assignment of the WHO 8th International Standard for factor VIII,
      concentrate (07/350).

PMID- 22458261
TI  - Ten-year follow-up observations of periapical and endodontic status in a Danish
      population.
AB  - AIM: To describe changes in periapical and endodontic status in a general adult
      Danish population examined in 1997, 2003 and 2008. METHODOLOGY: The study
      provides longitudinal, observational information on endodontic status for 327
      individuals who participated in three consecutive full-mouth radiographic
      examinations performed with an approximately 5-year interval. The collected data
      allow changes to be investigated within and between age-cohorts. RESULTS: The
      median number of teeth declined slightly, but the number of individuals with
      apical periodontitis (AP) and with root filled teeth increased. The number of
      teeth with AP and of teeth with root fillings increased, whereas the number of
      root filled teeth with AP was almost stable. The proportion of individuals who
      had no AP and the proportion of individuals who had no root fillings decreased
      during the 10-year observation period. The proportion of teeth with AP/individual
      increased steadily with age, unaffected by the different time periods.
      Differences were found between the age groups for the proportion of root filled
      teeth/individual where the younger age-cohorts had root fillings performed later
      in life and at a slower rate. In the old age-cohort, the proportion of lost
      teeth/individual was much larger and showed a stronger increase with age, than in
      the younger age-cohorts. CONCLUSION: The younger age-cohorts will probably never
      reach the proportion of root fillings or lost teeth seen in the oldest age
      cohort. However, it is disturbing that the proportion of teeth with AP/individual
      increased steadily with age, completely unaffected by the different time periods.

PMID- 22458262
TI  - Microbial profiles in saliva from children with and without caries in mixed
      dentition.
AB  - OBJECTIVE: The purpose of this study was to determine the bacterial profiles in
      saliva of the isolated children for studying caries etiology. MATERIALS AND
      METHODS:   Samples were collected from isolated children from 6 to 8years old
      including 20 caries-free (dmfs=0) (healthy) and 30 caries-active individuals
      (dmfs>8) (patients). 16S rRNA genes were amplified by PCR from bacterial DNA of
      saliva sample and labeled via incorporation of Cy3-dCTP in second nested PCR.
      After hybridization of labeled amplicons on HOMIM, the microarray slides were
      scanned and original data acquired from professional software. RESULTS:
      Collectively, 94 bacterial species or clusters representing six bacterial phyla
      and 30 genera were detected. A higher bacterial diversity was observed in
      patients than in healthy samples. Statistical analyses revealed eight species or
      clusters were detected more frequently in diseased patients than in healthy
      samples, while six different species were detected more frequently in healthy as
      compared to diseased patients. CONCLUSION: The diversity of microbe within saliva
      derived from isolated population increased in caries-active status, and there are
      some bacteria in salivary flora can be as candidate biomarkers for caries
      prognosis in mixed dentition. The imbalances in the resident microflora may be
      the ultimate mechanism of dental caries.

PMID- 22458263
TI  - The surfactant protein C mutation A116D alters cellular processing, stress
      tolerance, surfactant lipid composition, and immune cell activation.
AB  - BACKGROUND: Surfactant protein C (SP-C) is important for the function of
      pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C,
      cause sporadic and familial interstitial lung disease (ILD) in children and
      adults. Mutations mapping to the BRICHOS domain located within the SP-C
      proprotein result in perinuclear aggregation of the proprotein. In this study, we
      investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on
      cellular homeostasis. We also evaluated the ability of drugs currently used in
      ILD therapy to counteract these effects. METHODS: SP-CA116D was expressed in MLE
      12 alveolar epithelial cells. We assessed in vitro the consequences for cellular
      homeostasis, immune response and effects of azathioprine, hydroxychloroquine,
      methylprednisolone and cyclophosphamide. RESULTS: Stable expression of SP-CA116D
      in MLE-12 alveolar epithelial cells resulted in increased intracellular
      accumulation of proSP-C processing intermediates. SP-CA116D expression further
      led to reduced cell viability and increased levels of the chaperones Hsp90,
      Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular
      levels of phosphatidylcholine (PC) and increased lyso-PC levels. Treatment with
      methylprednisolone or hydroxychloroquine partially restored these lipid
      alterations. Furthermore, SP-CA116D cells secreted soluble factors into the
      medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+
      lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on
      neighboring cells in the alveolar space. CONCLUSIONS: We show that the A116D
      mutation leads to impaired processing of proSP-C in alveolar epithelial cells,
      alters cell viability and lipid composition, and also activates cells of the
      immune system. In addition, we show that some of the effects of the mutation on
      cellular homeostasis can be antagonized by application of pharmaceuticals
      commonly applied in ILD therapy. Our findings shed new light on the
      pathomechanisms underlying SP-C deficiency associated ILD and provide insight
      into the mechanisms by which drugs currently used in ILD therapy act.

PMID- 22458264
TI  - Proliposome powders for enhanced intestinal absorption and bioavailability of
      raloxifene hydrochloride: effect of surface charge.
AB  - The primary goal of the present study was to investigate the combined prospective
      of proliposomes and surface charge for the improved oral delivery of raloxifene
      hydrochloride (RXH). Keeping this objective, the present systematic study was
      focused to formulate proliposomes by varying the ratio of hydrogenated
      soyphosphatidylcholine and cholesterol. Furthermore, to assess the role of
      surface charge on improved absorption of RXH, anionic and cationic vesicles were
      prepared using dicetyl phosphate and stearylamine, respectively. The formulations
      were characterized for size, zeta potential and entrapment efficiency. The
      improved dissolution characteristics assessed from dissolution efficiency, mean
      dissolution rate were higher for proliposome formulations. The solid state
      characterization studies indicate the transformation of native crystalline form
      of the drug to amorphous and/or molecular state. The higher effective
      permeability coefficient and fraction absorbed in humans extrapolated from in
      situ single-pass intestinal absorption study data in rats provide an insight on
      the potential of proliposomes and cationic surface charge for augment in
      absorption across gastro intestinal barrier. To draw the conclusions, in vivo
      pharmacokinetic study carried out in rats indicate a threefold enhancement in the
      rate and extent of absorption of RXH from cationic proliposome formulation which
      unfurl the potential of proliposomes and role of cationic charge for improved
      oral delivery of RXH. 

PMID- 22458266
TI  - Social exclusion and people with intellectual disabilities: a rural-urban
      comparison.
AB  - BACKGROUND: Research suggests that social exclusion is a problem both for people
      with intellectual disabilities (ID) and for people living in rural areas. This
      may give rise to a double disadvantage for people with ID living in rural areas.
      Conversely, aspects of rural life such as community spirit and social support may
      protect against social exclusion in this population. This study was designed to
      compare a number of measures of social exclusion in adults with ID living in
      rural and urban areas, with the aim of identifying whether a double disadvantage
      exists. METHOD: Adults with ID were recruited from a rural and an urban area in
      Scotland. Participants participated in a face-to-face interview and their medical
      notes were accessed. Social exclusion was investigated using a number of measures
      comprising: daytime opportunities and physical access to community facilities
      (using part of the British Institute of Learning Disabilities questionnaire),
      recent contact with others and the quality of personal relationships (using a
      modified Interview Measure of Social Relationships questionnaire) and area
      deprivation by postcode (using the Scottish Index of Multiple Deprivation). The
      data were analysed using a series of binary logistic regression models that
      adjusted for variables including age, gender, level of ID, mental illhealth and
      common physical co-morbidities. RESULTS: A representative sample of adults with
      ID from rural (n = 39) and urban (n = 633) areas participated. Participants from
      rural areas were significantly more likely to have any regular daytime
      opportunity [odds ratio (OR) = 10.8, 95% CI = 2.3-51.5] including employment (OR
      = 22.1, 95% CI = 5.7-85.5) and attending resource centres (OR = 6.7, 95% CI = 2.6
      17.2) than were participants from urban areas. They were also more likely to have
      been on holiday (OR = 17.8, 95% CI = 4.9-60.1); however, were less likely to use
      community facilities on a regular basis. Participants from urban and rural areas
      had a similar number of contacts with other people in a wide range of situations,
      but the quality of relationships may have been less close in rural areas.
      Finally, participants lived in significantly less deprived areas when in rural
      compared with urban areas (Mann-Whitney U = 7826, Z = -3.675, P <= 0.001).
      CONCLUSIONS: These results suggest that adults with ID living in rural areas have
      better opportunities and live in less deprived areas than adults with ID living
      in urban areas. However, they may not hold such positive or close relationships,
      and this may be important when considering the subjective experience of social
      exclusion.

PMID- 22458267
TI  - Quality of life in men receiving radiotherapy and neo-adjuvant androgen
      deprivation for prostate cancer: results from a prospective longitudinal study.
AB  - AIM: To report a study measuring the quality of life and side effects in men
      receiving radiotherapy and hormone ablation for prostate cancer up to 1 year
      after treatment. BACKGROUND: Prostate cancer incidence is increasing with the
      result that more men are living longer with the disease and the side effects of
      treatment. It is important to know the effects this has on their quality of life.
      DESIGN: Survey. METHOD: Between September 2006-September 2007, all men who were
      about to undergo radical conformal radiotherapy +/- neo-adjuvant androgen
      deprivation for localized prostate cancer were invited to participate in the
      study; 149 men were recruited. They completed the European Organization on
      Research and Treatment of Cancer quality of life questionnaire C-30 and Prostate
      Cancer module PR25 at four time-points. RESULTS: At 4-6 weeks after radiotherapy,
      participants experienced the biggest relative decline in global quality of life,
      social, physical, and role functioning and an increase in treatment side effects.
      At 6 months postradiotherapy the majority of men experienced an improvement in
      their side effects. However, a minority of men were experiencing severe side
      effects of radiotherapy at 1 year post-treatment. Single men and men who had a
      low quality of life prior to radiotherapy, reported a lower quality of life at 1
      year after treatment in comparison to married men. CONCLUSION: Men with prostate
      cancer suffer limitations due to the symptoms they experience and disruption to
      their quality of life. It is essential that nurses develop and deliver follow-up
      care which is flexible and appropriate to the individual needs of these men.

PMID- 22458265
TI  - Viral hemorrhagic fevers: advancing the level of treatment.
AB  - The management of viral hemorrhagic fevers (VHFs) has mainly focused on strict
      infection control measures, while standard clinical interventions that are
      provided to patients with other life-threatening conditions are rarely offered to
      patients with VHFs. Despite its complexity, a proper clinical case management of
      VHFs is neither futile nor is it lacking in scientific rationale. Given that
      patient outcomes improve when treatment is started as soon as possible,
      development and implementation of protocols to promptly identify and treat
      patients in the earliest phases of diseases are urgently needed. Different
      pharmacological options have been proposed to manage patients and, as for other
      life-threatening conditions, advanced life support has been proved effective to
      address multiorgan failure. In addition, high throughput screening of small
      molecular libraries has emerged as a novel promising way to find new candidates
      drugs for VHFs therapy and a relevant number of new molecules are currently under
      investigation. Here we discuss the current knowledge about VHF clinical
      management to propose a way to step up the approach to VHFs beyond the mere
      application of infection control measures.

PMID- 22458268
TI  - The effects of similarity in sexual excitation, inhibition, and mood on sexual
      arousal problems and sexual satisfaction in newlywed couples.
AB  - INTRODUCTION: Despite the importance of sexuality for romantic relationships,
      there has been little research attention to individual differences and dyadic
      variables, including couple similarity, and their association with sexual
      problems and satisfaction. AIM: The current study examined the effects of the
      propensity for sexual inhibition and sexual excitation scales (SIS/SES) and the
      effects of different mood states on sexuality (Mood and Sexuality Questionnaire
      [MSQ]), at both the individual and the dyad level, on sexual arousal problems and
      sexual satisfaction. METHODS: Similarity in SIS/SES and MSQ was measured in a
      nonclinical sample of 35 newlywed couples and operationally defined as the within
      couple, z-transformed correlations between the two partners' item responses. MAIN
      OUTCOME MEASURES: Sexual arousal problems were assessed using self-report
      measures (Demographic and Sexual History Questionnaire) and focused on the past 3
      months. Sexual satisfaction was assessed using the Global Measure of Sexual
      Satisfaction. RESULTS: Regression analyses revealed that greater similarity in
      the effects of anxiety and stress on sexuality was associated with more reported
      sexual arousal problems of wives. In contrast, the husbands' sexual arousal
      problems were related only to their own higher SIS1 scores. Higher SES scores
      predicted lower sexual satisfaction for both husbands and wives. Wives who
      reported strong positive mood effects on their sexuality indicated greater sexual
      satisfaction, while husbands who were more similar to their wives in the effect
      of positive moods on sexuality indicated greater sexual satisfaction.
      CONCLUSIONS: The findings show that, above and beyond one's own sexual
      propensities, similarity in various aspects of sexuality predicts sexual problems
      (more so in women) and sexual satisfaction (in both men and women).

PMID- 22458270
TI  - Optimizing the conditions for in vitro maturation and artificial activation of
      sika deer (Cervus nippon hortulorum) oocytes.
AB  - With the goal of establishing experimental protocols for cloning sika deer,
      various conditions for in vitro maturation (IVM) and artificial activation of
      sika deer oocytes were examined. In vitro maturation was evaluated in seven
      different culture media. The highest rate of oocyte maturation was 75.4% in 10
      MUg/ml follicle-stimulating hormone (FSH), 1 MUg/ml LH, 0.2 mm cysteamine and 50
      ng/ml epidermal growth factor (EGF) after 24 h of IVM. The efficiency after 24 h
      of IVM did not differ significantly (p > 0.05) from that observed after 20 h.
      Cysteamine (0.2 mm) significantly increased the maturation rates after 20 h (from
      59.1% to 67.2%, p < 0.05) and after 24 h (from 63.2% to 71.6%, p < 0.05) of IVM.
      The IVM rates of oocytes collected during the oestrous season (75.4%) and the
      anoestrous season (23.3%) were significantly different at 24 h. The 20 MUg/ml
      FSH, 2 MUg/ml LH, 0.4 mm cysteamine and 100 ng/ml EGF significantly increased the
      maturation rates (from 23.3% to 54.2%, p < 0.01) at 24 h during the anoestrous
      season. For the activation experiments, the most effective method was chemical
      activation [ionomycin + 6-dimethylaminopurine (6-DMAP)], which promoted the
      development of sika deer oocytes to the blastocyst stage (32.4%). Our results
      indicate that in vitro matured sika deer oocytes are good candidates for
      parthenogenetic activation and that chemical treatment is needed for relatively
      efficient activation of the oocytes. These optimized conditions for IVM and
      parthenogenetic activation may be useful for efforts to restore populations of
      the endangered sika deer using the somatic cell nuclear transfer technique.

PMID- 22458271
TI  - Texture of cellulose microfibrils of root hair cell walls of Arabidopsis
      thaliana, Medicago truncatula, and Vicia sativa.
AB  - Cellulose is the most abundant biopolymer on earth, and has qualities that make
      it suitable for biofuel. There are new tools for the visualisation of the
      cellulose synthase complexes in living cells, but those do not show their
      product, the cellulose microfibrils (CMFs). In this study we report the
      characteristics of cell wall textures, i.e. the architectures of the CMFs in the
      wall, of root hairs of Arabidopsis thaliana, Medicago truncatula and Vicia sativa
      and compare the different techniques we used to study them. Root hairs of these
      species have a random primary cell wall deposited at the root hair tip, which
      covers the outside of the growing and fully grown hair. The secondary wall starts
      between 10 (Arabidopsis) and 40 (Vicia) MUm from the hair tip and the CMFs make a
      small angle, Z as well as S direction, with the long axis of the root hair. CMFs
      are 3-4 nm wide in thin sections, indicating that single cellulose synthase
      complexes make them. Thin sections after extraction of cell wall matrix, leaving
      only the CMFs, reveal the type of wall texture and the orientation and width of
      CMFs, but CMF density within a lamella cannot be quantified, and CMF length is
      always underestimated by this technique. Field emission scanning electron
      microscopy and surface preparations for transmission electron microscopy reveal
      the type of wall texture and the orientation of individual CMFs. Only when the
      orientation of CMFs in subsequent deposited lamellae is different, their density
      per lamella can be determined. It is impossible to measure CMF length with any of
      the EM techniques.

PMID- 22458272
TI  - Does metabolic syndrome influence bioprosthetic mitral valve degeneration and
      reoperation rate?
AB  - BACKGROUND: Evidence suggests that metabolic syndrome (MbS) is associated with
      early senescence of bioprosthetic aortic valve prostheses. The purpose of this
      study was to determine whether MbS is also associated with accelerated failure of
      bioprosthetic valves prostheses in the mitral position. METHODS: Records of all
      patients undergoing bioprosthetic mitral valve replacement (MVR) from 1993 to
      2000 were reviewed. RESULTS: Of 114 patients undergoing bioprosthetic MVR, 48
      (42%) had MbS. Mean age was 73 years (vs. 74 years for no MbS). Patients
      underwent MVR for regurgitation (n = 97; 85%), stenosis (n = 12; 11%), or mixed
      lesions (n = 4; 4%). Etiology was degenerative (n = 35; 32%), rheumatic (n = 26;
      24%), ischemic (n = 30; 28%), calcific (n = 9; 8%), and endocarditis (n = 8; 8%).
      Mean follow-up was 4.5 years. Overall survival at 5 and 10 years was 56% and 26%,
      respectively. Survival was similar between groups (p = 0.15). Five patients (2
      MbS; 4% vs. 3 no MbS; 5%) required mitral reoperation at a mean of 3.8 years
      after initial MVR. The risk of prosthetic valve failure was not different between
      groups (p = 0.66). Despite no initial difference in transmitral gradients,
      gradients beyond five-year follow-up were greater for those with MbS (6.8 mmHg
      MbS vs. 4.7 mmHg no MbS, p = 0.007). Independent predictors of gradient
      progression beyond two years were MbS (p = 0.027) and female gender (p = 0.012).
      There were no significant differences in valve area, regurgitation, or ejection
      fraction. CONCLUSIONS: Although overall survival following bioprosthetic MVR is
      challenging, MbS did not predict diminished survival or excess reoperative risk
      compared to non-MbS patients. The trend toward more rapid progression of
      transprosthetic gradients in MbS patients warrants further investigation.

PMID- 22458269
TI  - Translating basic science insight into public health action for multidrug- and
      extensively drug-resistant tuberculosis.
AB  - Multidrug (MDR)- and extensively drug-resistant (XDR) tuberculosis (TB) impose a
      heavy toll of human suffering and social costs. Controlling drug-resistant TB is
      a complex global public health challenge. Basic science advances including
      elucidation of the genetic basis of resistance have enabled development of new
      assays that are transforming the diagnosis of MDR-TB. Molecular epidemiological
      approaches have provided new insights into the natural history of TB with
      important implications for drug resistance. In the future, progress in
      understanding Mycobacterium tuberculosis strain-specific human immune responses,
      integration of systems biology approaches with traditional epidemiology and
      insight into the biology of mycobacterial persistence have potential to be
      translated into new tools for diagnosis and treatment of MDR- and XDR-TB. We
      review recent basic sciences developments that have contributed or may contribute
      to improved public health response.

PMID- 22458273
TI  - A modified chordal transfer technique to treat anterior mitral leaflet prolapse.
AB  - Chordal transfer from the intact posterior mitral leaflet (PML) to the anterior
      mitral leaflet (AML) is an effective way to correct anterior leaflet prolapse and
      provides good long-term results. However, it is difficult to determine the
      accurate segment of the PML which needs to be transferred and the suture point of
      the leaflets. We describe a modified technique to determine the correct segment
      that needs to be transferred to effectively correct AMLs with elongated or
      ruptured chordae. This technique renders performing chordal transfer easier and
      more accurate.

PMID- 22458274
TI  - Surgical management of cardiac liposarcomas.
AB  - Cardiac liposarcoma is an uncommon tumor with a poor prognosis. The diagnosis and
      surgical treatment of this malignant tumor are the subject of this review.

PMID- 22458275
TI  - Transatrial transcatheter tricuspid valve-in-valve technique.
AB  - A novel approach to reoperative tricuspid valve replacement using the
      transcatheter valve-in-valve concept is studied. Three consecutive transapica
      transcatheter tricuspid Sapien balloon-expandable valve-in-valve cases, including
      the first-in-man case, are described. The technical lessons learnt and the
      clinical outcomes are elaborated.

PMID- 22458276
TI  - Indirect re-implantation of the left coronary artery during aortic surgery.
AB  - OBJECTIVE: Indirect re-implantation of the left coronary artery (LCA) via an
      interposition graft simplifies difficult LCA re-implantation during aortic root
      replacement. Little information exists regarding the results of this technique.
      In this study, we report our experience. METHODS: Between January 2001 and July
      2008, of 82 aortic root replacements, 24 (mean age 48.2 years, 83% male) used the
      indirect re-implantation technique. All case notes were retrospectively analyzed.
      Indications for operation were; aortic root aneurysm (n = 16), acute dissection
      (n = 6), existent homograft calcification (n = 1), failed Ross procedure (n = 1).
      Reasons for indirect re-implantation were: difficult LCA mobilization secondary
      to previous cardiac surgery (n = 7), short left main stem (n = 6), acute
      dissection (n = 6), adherence to surrounding tissues (n = 5). All patients had
      yearly CT or MRI follow-up. RESULTS: Mechanical and tissue valved conduits were
      implanted in 22 and two patients, respectively. Ten millimeters (n = 17) or 8 mm
      (n = 7) Dacron grafts were used for LCA re-implantation. Thirty-day mortality was
      12.5%. Postoperative complications were: re-opening for bleeding (n = 2),
      pericardial effusion (n = 4), renal failure (n = 1). Over a median follow-up of
      26 months (range 4 to 81), one developed a false aneurysm at the right coronary
      artery anastomosis five months postoperatively, which was subsequently repaired.
      All interposition grafts remained patent on MRI or CT. There were six late
      deaths. At median follow-up survival rate was 71%. CONCLUSIONS: The indirect re
      implantation of the LCA during aortic root replacements is a reliable, safe, and
      effective method in dealing with the LCA in difficult circumstances. Survival at
      26 months is equivalent to other series of similar patients.

PMID- 22458277
TI  - Effective cerebral protection using near-infrared spectroscopy monitoring with
      antegrade cerebral perfusion during aortic surgery.
AB  - OBJECTIVE: Antegrade cerebral perfusion (ACP) under moderate hypothermia may
      improve cerebral protection. Intraoperative measurement of cerebral regional
      oxygen saturations (rSO2) using near-infrared spectroscopy (NIRS) can provide
      accurate monitoring of cerebral perfusion during ACP. We evaluated the role,
      outcomes, and advantages of using NIRS in providing effective cerebral protection
      with ACP. METHODS: Between May 2006 and March 2009, 27 patients (mean age 60%,
      93% elective) underwent ascending aorta replacement with ACP monitored by NIRS.
      ACP was established through the right axillary artery (n = 26). All patients had
      continuous intraoperative measurement of both anterior cerebral rSO2 using NIRS
      (INVOS; Somanetics Corporation, Troy, MI, USA). Posterior cerebral perfusion was
      measured using left radial artery pressures. Quality of life (QoL) was assessed
      using a Short Form 36 questionnaire. RESULTS: Mean cardiopulmonary bypass and
      aortic cross clamp time were 169 +/- 27 and 95 +/- 22 minutes, respectively. Mean
      ACP rate of 1.27 +/- 0.35 L/min provided a mean left radial artery pressure of at
      least 60 mmHg. All patients' cerebral rSO2 were maintained above their baseline
      using NIRS. Mean ACP time was 14.3 +/- 2.6 minutes at a mean core temperature of
      23.4  degrees C +/- 2.0  degrees C. Temporary neurological deficit was observed
      in two patients (7.4%). No permanent neurological dysfunction was observed.
      Thirty-day mortality was 3.7%. At median follow-up of 18.3 (interquartile range
      10.8 to 23.3) months survival was 92% and mean norm-based QoL score was above
      average at 52.5 +/- 6.5. CONCLUSION: Cerebral rSO2 and left radial artery
      pressure monitoring with ACP during aortic surgery provides accurate measurement
      of cerebral perfusion resulting in minimal neurological and perioperative
      complications and good midterm QoL outcomes.

PMID- 22458278
TI  - Reverse elephant trunk technique: a novel approach to pseudoaneurysm repair.
AB  - Traditional surgical access to the upper descending aorta is via a left
      thoracotomy. For postcoarctation pseudoaneurysm repair, this approach is
      difficult because of the risk of rupture while dissecting the aorta for proximal
      and distal control. Access from a median sternotomy may be safer, but is
      difficult because of the depth of the wound and because of the angle of approach
      to the distal aspect of the repair site. We describe a novel approach via a
      median sternotomy incision, using circulatory arrest and "elephant trunk"
      principles to achieve tube graft replacement of the aneurysmal section of aorta.

PMID- 22458279
TI  - Emergent pectus excavatum repair after aortic root replacement in Marfan patient.
AB  - Chest wall deformities, including pectus excavatum, can complicate cardiac
      operations by impeding sternal entry and cardiac exposure and by affecting
      cardiac hemodynamic performance. We describe a patient with Marfan syndrome who
      underwent elective replacement of an aortic root aneurysm. The patient required a
      simultaneous, unplanned, emergent repair of her severe pectus excavatum because
      of hemodynamic instability after sternal closure. The success of this procedure
      suggests that emergent single-stage repair of pectus excavatum should be
      considered when median sternotomy closure precipitates hemodynamic instability in
      such patients.

PMID- 22458280
TI  - Spinal cord injury after ascending aorta and aortic arch replacement combined
      with antegrade stent grafting: role of postoperative cerebrospinal fluid
      drainage.
AB  - Ascending aorta and aortic arch replacement combined with antegrade stent
      grafting of the descending thoracic aorta represents an emerging hybrid surgical
      approach for complex and extensive thoracic aortic disease. We present a case of
      a patient at low risk for spinal cord ischemia who underwent hybrid thoracic
      aortic surgery (aortic arch replacement and E-vita prosthesis implantation) and
      developed a spinal cord injury (SCI) after the intervention. Treatment aimed at
      increasing spinal cord perfusion pressure with the aid of cerebrospinal fluid
      (CSF) drainage was effective in recovering neuromuscular function.

PMID- 22458281
TI  - Mid-term results after correction of type I and type II persistent truncus
      arteriosus in older patients.
AB  - OBJECTIVE: This study aims to analyze long-term results after correction of type
      I and type II truncus arteriosus in older patients operated in one institution
      over five years. METHODS: Between 2006 and 2010, 12 patients, median age 4 years,
      underwent repair of truncus arteriosus. Repair with reconstruction of the right
      ventricular to pulmonary artery continuity was performed using a valved conduit
      in 12 patients. RESULTS: There was no early mortality. All patients are alive
      with their original conduit 0.6 to 5 years after correction. No patients required
      reoperations for conduit dysfunction. Recent clinical examination was undertaken
      in all patients and they are in good condition. CONCLUSIONS: Though mean age at
      operation was higher in this study than published results, the operation should
      be performed if the pulmonary vascular resistance is under 8 units.m(2) before
      operation.

PMID- 22458282
TI  - Surgical repair of a submitral aneurysm in a three-year-old child.
AB  - Submitral aneurysm (SMA) is a rare anomaly occurring adjacent to the posterior
      leaflet of the mitral valve. It usually presents in young adults and it is
      uncommon in the pediatric age group. We report one case of SMA in a three-year
      old child and its successful surgical management.

PMID- 22458283
TI  - Interrupted left aortic arch and isolated right subclavian artery from the right
      pulmonary artery.
AB  - We report a 10-day-old newborn, weighing 2.9 kg with an interrupted left aortic
      arch type B, a large subarterial ventricular septal defect and a right ductus
      connecting the right pulmonary artery to an isolated right subclavian artery. The
      patient underwent successful total surgical repair and the isolated right
      subclavian artery was ligated. He was discharged from hospital without
      complication and maintains excellent perfusion to the right arm via collaterals.

PMID- 22458284
TI  - Defying death: can new ECMO technology improve the outcomes of postcardiotomy
      shock?

PMID- 22458285
TI  - Left ventricular assist device implantation in a patient who had previously
      undergone apical myectomy for hypertrophic cardiomyopathy.
AB  - Apical hypertrophy is a rare variant of hypertropic cardiomyopathy. These
      patients may present with end-stage congestive heart failure subsequent to long
      standing diastolic dysfunction. We report the technique for left ventricular
      assist device insertion in a patient with previous apical myectomy for
      hypertrophic cardiomyopathy.

PMID- 22458286
TI  - Assessing the immediate and sustained effectiveness of circular epicardial
      surgical ligation of the left atrial appendage.
AB  - BACKGROUND/AIM: Obliterating the left atrial appendage from systemic circulation
      in patients with atrial fibrillation has been proposed to reduce thromboembolic
      events. The goal of this study was to assess the effectiveness of a circular
      method of epicardial surgical ligation in obliterating the left atrial appendage
      and maintaining sustained exclusion. METHODS: Patients with permanent atrial
      fibrillation and an indication for elective cardiac surgery were enrolled. All
      patients underwent preoperative cardiac gated computerized tomography (CT) and
      transesophageal echocardiography (TEE). During the cardiac procedure circular
      ligation of the appendage was performed. RESULTS: Twelve patients, mean (SD) age
      65 (12) years completed the study. Intraoperative TEE demonstrated all patients
      (12/12) had complete postligation occlusion of the left atrial appendage. At
      three-month follow-up, cardiac gated CT demonstrated that 75% (9/12) of the
      patients had communication of contrast dye from the left atrial appendage to body
      of left atrium. Left atrial appendage orifice area and volume were reduced from
      mean (SD) (5.5 cm(2) [1.8] to 0.5 cm(2) [0.4] p = 0.002) and (14.0 cm(3) [8.3] to
      2.7 cm(3) [1.3] p = .005) postligation, respectively. No clinically significant
      thromboembolic events were reported. CONCLUSIONS: Epicardial suture ligation of
      the left atrial appendage resulted in successful intra-operative exclusion on
      TEE; however, a significant portion of patient's demonstrated communication of
      contrast on CT. This is suggestive of incomplete long-term exclusion. The
      clinical significance of reduction in left atrial appendage orifice area and
      volume with a persistent communication requires further study.

PMID- 22458287
TI  - Assessing educational outcomes in middle childhood: validation of the Teacher
      Academic Attainment Scale.
AB  - AIM: Assessing educational outcomes in high-risk populations is crucial for
      defining long-term outcomes. As standardized tests are costly and time-consuming,
      we assessed the use of the Teacher Academic Attainment Scale (TAAS) as an outcome
      measure. METHOD: Three hundred and forty three children in mainstream schools
      aged 10 to 11 years (144 males, 199 females; 190 extremely preterm and 153 term;
      mean age 10 y 9 mo, SD 5.5 mo, range 9 y 8 mo-12 y 3 mo) were assessed using the
      reading and mathematics scales of the criterion standard Wechsler Individual
      Achievement Test, 2nd (UK) edition (WIAT-II). Class teachers completed the TAAS,
      a seven-item questionnaire for assessing academic attainment. The TAAS was also
      completed at 6 years of age for 266 children. RESULTS: Cronbach's alpha 0.95
      indicated excellent internal consistency, and the correlation between TAAS scores
      at 6 and 11 years indicated good test-retest reliability (r=0.77, p<0.001).
      Significantly higher TAAS scores for term vs preterm children demonstrated
      discriminative validity. TAAS scores at 6 and 11 years were significantly
      correlated with WIAT-II reading (r=0.69 and 0.75, p<0.001) and mathematics
      (r=0.75 and 0.82, p<0.001) scores, demonstrating good predictive and concurrent
      validity respectively. TAAS scores of <2.5 were good predictors of learning
      difficulties. INTERPRETATION: The TAAS is a brief, psychometrically sound teacher
      report of academic attainment that yields continuous and categorical outcomes. It
      provides a cost- and time-efficient outcome measure for large-scale studies.

PMID- 22458288
TI  - Health and sexual outcomes of women who have experienced forced or coercive sex.
AB  - Previous research has linked women's history of experiencing sexual assault with
      negative health outcomes; however, much of this research is over a decade old.
      Furthermore, little research has examined the relationship between sexual assault
      and women's sexuality. In the current study the authors aimed to assess the
      relation of experiencing sexual assault to women's health and sexuality and the
      relation of repeat victimization by multiple different perpetrators to such
      outcomes. Data were collected from a convenience sample of 2,915 women using an
      online questionnaire. Nearly half (n = 1,394, 47.8%) indicated having experienced
      forced or coercive sex. Women who had experienced forced or coercive sex were
      more likely to report negative health outcomes (Adj. OR = 1.56; 95% CI: 1.35
      1.82, p < .001) and some negative sexual outcomes compared to women without a
      history of forced or coercive sex. Similarly, women who experienced repeat
      victimizations by multiple different perpetrators were even more likely to report
      negative health outcomes (Adj. OR = 1.43; 95% CI: 1.28-1.59, p < .001) as well as
      some negative sexual outcomes. Healthcare providers should be aware of the
      relation of sexual assault to health and sexuality and continue to address health
      and sexuality issues associated with sexual assault for their patients.

PMID- 22458290
TI  - Lower prevalence of cigarette and waterpipe smoking, but a higher risk of
      waterpipe dependence in Lebanese adult women than in men.
AB  - The objective of this study was to evaluate whether nicotine dependence was
      higher in Lebanese women smokers compared with men smokers. Data were taken from
      a national cross-sectional study. Lebanese residents aged >= 40 years were
      enrolled between October 2009 and September 2010. After informed consent,
      participants answered a standardized questionnaire about smoking behaviors and
      dependence (measured by the Fagerstrom-Test-Nicotine-Dependence for cigarettes
      and the Lebanon-Waterpipe-Dependence-Scale 11 for waterpipes): 1,066 males and
      1,134 females were interviewed. 58.7% versus 42.9% of them, respectively, ever
      smoked cigarettes, while 6.9% versus 6.7% ever smoked a waterpipe (p < 0.001).
      Moreover, 57.5% in male versus 49.1% in female cigarette smokers (p = 0.041),
      35.9% versus 51.6% in waterpipe smokers (p = 0.076), and 67.9% versus 43.6% in
      mixed smokers were tobacco dependent. A dose-effect relationship was observed
      with increased rates of women versus men with waterpipe dependence) and an
      increased odds of dependence among women in multivariable analysis (ORa = 2.28).
      Positive (smoking waterpipe for pleasure and conviviality) and negative (smoking
      waterpipe to relax nerves and improve morale) reinforcements were significantly
      more frequent in women, while no significant sex difference was observed for
      nicotine dependence or psychological craving. In exclusive waterpipe smokers,
      significantly higher respiratory diseases and symptoms prevalences were found in
      females compared with males. Women who smoke waterpipes should receive attention
      during tobacco health education and smoking cessation.

PMID- 22458289
TI  - Prevalence and predictors of sexually transmitted infections in hazardously
      drinking incarcerated women.
AB  - Incarcerated women are at high risk for sexually transmitted infections. Left
      untreated, these infections can have severe adverse health effects. In this study
      the authors present prevalence rates of trichomonas, chlamydia, and gonorrhea,
      and factors related to having a sexually transmitted infection in a sample of 245
      hazardously-drinking incarcerated women who reported heterosexual intercourse in
      the previous 3 months. Vaginal swabs were collected following the self-report
      baseline assessment. Participants averaged 34.0 (+/-8.8) years of age; 174
      (71.3%) were non-Hispanic Caucasian, 47 (19.3%) were African-American, 17 (7.0%)
      were Hispanic, and 6 (2.5%) were of other racial or ethnic origins. Twenty-three
      percent of participants tested positive for chlamydia, trichomonas, or gonorrhea.
      Being African-American, more frequent sex with a casual partner, and reporting
      more than one male partner were significantly positively related to sexually
      transmitted infection, while more frequent sex with a main partner was inversely
      related. Due to the high rates of infection in this population, jail admission
      provides a public health opportunity to access a concentrated group of sexually
      transmitted infectious women. Sexually transmitted infection testing targeted at
      specific demographic factors, for instance younger age, will miss infected women.
      Risky sexual partnerships, as well as the benefit of maintaining stable main
      partnerships may be important topics during sexually transmitted infection
      prevention interventions.

PMID- 22458291
TI  - Provision of contraceptive services to homeless women: results of a survey of
      health care for the homeless providers.
AB  - Homeless women have both a higher rate of pregnancy and a higher proportion of
      unintended pregnancies than other American women. The authors sought to learn
      about contraception services offered by providers of health care to homeless
      women and barriers to provision of long-acting, reversible contraception in these
      settings. A survey of the 31 member organizations in the national Health Care for
      the Homeless Practice-Based Research Network was conducted, inquiring about
      services provided and barriers to service provision. Among the 20 responding
      organizations (65% response rate), 17 directly provided contraceptive services;
      two referred patients elsewhere, and one provided no contraceptive services. All
      17 that provided such services provided condoms; 15 provided oral contraceptives;
      14 provided injectable contraception; 6 provided intrauterine devices, and 2
      provided contraceptive implants. Barriers to providing the last two methods
      included lack of provider training, lack of resources for placement, costs, and
      concerns about complications. The present survey results suggested very limited
      access for homeless women across the country to the two most effective means of
      long-acting, reversible contraception. Modest investments of resources could
      reduce a number of barriers to providing these services.

PMID- 22458292
TI  - Empowerment beliefs and intention to uptake cervical cancer screening: three
      psychosocial mediating mechanisms.
AB  - Three studies tested if the associations between women's empowerment beliefs and
      intentions to attend cervical cancer screening could be explained by mediating
      psychological mechanisms: control-related beliefs, well being-related beliefs,
      and beliefs and evaluations referring to social functioning. Data were collected
      from January to March 2011 in the rural and urban areas across regions of Poland.
      Study 1 (N = 386) indicated that women with strong empowerment harbored stronger
      self-efficacy and beliefs that screening participation would make them feel in
      control of their own health and body. These two types of cognitions were, in
      turn, associated with stronger cervical cancer screening intentions. Results of
      Study 2 (N = 527) confirmed three significant well being-related mediators in the
      relationship between empowerment beliefs and cervical cancer screening: perceived
      benefits of screening related to well being, appearance satisfaction, discomfort-
      and shame-related barriers for screening. Finally, Study 3 (N = 424) showed that
      empowerment enabled receiving higher social support for cervical cancer
      screening, promoted perceiving fewer barriers for cervical cancer screening
      related communication and more social benefits of engaging in cervical cancer
      screening. Support for cervical cancer screening, social barriers, and benefits
      were, in turn, related to screening intentions. Across the studies similar shares
      of intention variance were explained, and thus the hypothesized mediating
      mechanisms may have similar explanatory power.

PMID- 22458293
TI  - The impact of gender roles on health.
AB  - The present research focused on a sample of Spanish undergraduate women and men
      to evaluate whether gender was related to substance use and chronic illness. This
      research examined the associations of conformity to masculine norms for men and
      conformity to feminine norms for women with substance use in chronic illnesses.
      Spanish male (n = 226) and female (n = 234) college undergraduates completed
      measures of chronic diseases, alcohol and tobacco consumption, and conformity to
      gender norms. Multivariable regression analyses demonstrated that being female
      was related to lower alcohol and cigarette consumption but a greater rate of
      chronic illnesses. Although masculinity did not explain the rate of chronic
      illnesses, specific feminine and masculine gender norms were related to alcohol
      and tobacco use and prevalence of chronic diseases. The present study provides
      insights for further cross-cultural psychological studies on the mediating effect
      of self-reported conformity to gender norms (rather than only sex) on health.
      Limitations and implications are discussed.

PMID- 22458295
TI  - Workplace-based assessment as an educational tool. Guide supplement 31.5-
      Viewpoint.

PMID- 22458294
TI  - The oral-systemic personalized medicine model at Marshfield Clinic.
AB  - Periodontal disease and diabetes, two diseases that have achieved epidemic
      status, share a bidirectional relationship driven by micro-inflammatory
      processes. The present review frames the current understanding of the
      pathological processes that appear to link these diseases and advances the
      hypothesis that reversal of the epidemic is possible through application of
      interdisciplinary intervention and advancement of oral-systemic personalized
      medicine. An overview of how Marshfield Clinic's unique clinical, informatics and
      bio-repository resources and infrastructures are being aligned to advance oral
      systemic personalized medicine is presented as an interventional model with the
      potential to reverse the epidemic trends seen for these two chronic diseases over
      the past several decades. The overall vision is to engineer a transformational
      shift in paradigm from 'personalized medicine' to 'personalized health'.

PMID- 22458296
TI  - Targeted gene inactivation reveals a functional role of calpain-1 in platelet
      spreading.
AB  - BACKGROUND: Calpains are implicated in a wide range of cellular functions
      including the maintenance of hemostasis via the regulation of cytoskeletal
      modifications in platelets. OBJECTIVES: Determine the functional role of calpain
      isoforms in platelet spreading. METHODS AND RESULTS: Platelets from calpain-1(-/
      ) mice show enhanced spreading on collagen- and fibrinogen-coated surfaces as
      revealed by immunofluorescence, differential interference contrast (DIC) and
      scanning electron microscopy. The treatment of mouse platelets with MDL, a cell
      permeable inhibitor of calpains 1/2, resulted in increased spreading. The PTP1B
      mediated enhanced tyrosine dephosphorylation in calpain-1(-/-) platelets did not
      fully account for the enhanced spreading as platelets from the double knockout
      mice lacking calpain-1 and PTP1B showed only a partial rescue of the spreading
      phenotype. In non-adherent platelets, proteolysis and GTPase activity of RhoA and
      Rac1 were indistinguishable between the wild-type (WT) and calpain-1(-/-)
      platelets. In contrast, the ECM-adherent calpain-1(-/-) platelets showed higher
      Rac1 activity at the beginning of spreading, whereas RhoA was more active at
      later time points. The ECM-adherent calpain-1(-/-) platelets showed an elevated
      level of RhoA protein but not Rac1 and Cdc42. Proteolysis of recombinant RhoA,
      but not Rac1 and Cdc42, indicates that RhoA is a calpain-1 substrate in vitro.
      CONCLUSIONS: Potentiation of the platelet spreading phenotype in calpain-1(-/-)
      mice suggests a novel role of calpain-1 in hemostasis, and may explain the normal
      bleeding time observed in the calpain-1(-/-) mice.

PMID- 22458298
TI  - Clinical implications of pleural effusions in ovarian cancer.
AB  - The pleural cavity constitutes the most frequent extra-abdominal metastatic site
      in ovarian carcinoma (OC). In patients with OC and pleural effusions, a positive
      fluid cytology is required for a stage IV diagnosis. Unfortunately, about 30% of
      malignant pleural effusions exhibit false-negative cytological pleural fluid
      results. In those circumstances, exploratory video-assisted thoracoscopic surgery
      (VATS) serves as a diagnostic, staging and even therapeutic modality. Maximal (no
      visible disease) or, at least, optimal (no residual implant greater than 1 cm)
      cytoreduction should be the primary surgical goal in stage IV OC patients. This
      is due to residual tumour after cytoreductive surgery being one of the most
      important factors impacting on survival. Although malignant pleural effusions do
      not preclude abdominal surgical debulking, excision of gross pleural nodules may
      be necessary to achieve optimal cytoreduction. VATS quantifies pleural tumour
      burden and allows for intrathoracic cytoreduction or, if the latter is not
      feasible, ensures that abdominal surgery is not unnecessarily performed on women
      in whom gross tumour would still remain in the pleural space afterwards. Taxane
      platinum neoadjuvant chemotherapy should be offered to this group. Patients with
      tumour extension into the pleural space have a median overall survival of 2
      years.

PMID- 22458297
TI  - Superfolder GFP reporters validate diverse new mRNA targets of the classic porin
      regulator, MicF RNA.
AB  - MicF is a textbook example of a small regulatory RNA (sRNA) that acts on a trans
      encoded target mRNA through imperfect base pairing. Discovery of MicF as a post
      transcriptional repressor of the major Escherichia coli porin OmpF established
      the paradigm for a meanwhile common mechanism of translational inhibition,
      through antisense sequestration of a ribosome binding site. However, whether MicF
      regulates additional genes has remained unknown for almost three decades. Here,
      we have harnessed the new superfolder variant of GFP for reporter-gene fusions to
      validate newly predicted targets of MicF in Salmonella. We show that the
      conserved 5' end of MicF acts by seed pairing to repress the mRNAs of global
      transcriptional regulator Lrp, and periplasmic protein YahO, while a second
      targeting region is also required to regulate the mRNA of the lipid A-modifying
      enzyme LpxR. Interestingly, MicF targets lpxR at both the ribosome binding site
      and deep within the coding sequence. MicF binding in the coding sequence of lpxR
      decreases mRNA stability through exacerbating the use of a native RNase E site
      proximal to the short MicF-lpxR duplex. Altogether, this study assigns the
      classic MicF sRNA to the growing class of Hfq-associated regulators that use
      diverse mechanisms to impact multiple loci.

PMID- 22458299
TI  - Towards more reliable automated multi-dose dispensing: retrospective follow-up
      study on medication dose errors and product defects.
AB  - To date, little is known on applicability of different types of pharmaceutical
      dosage forms in an automated high-speed multi-dose dispensing process. The
      purpose of the present study was to identify and further investigate various
      process-induced and/or product-related limitations associated with multi-dose
      dispensing process. The rates of product defects and dose dispensing errors in
      automated multi-dose dispensing were retrospectively investigated during a 6
      months follow-up period. The study was based on the analysis of process data of
      totally nine automated high-speed multi-dose dispensing systems. Special
      attention was paid to the dependence of multi-dose dispensing errors/product
      defects and pharmaceutical tablet properties (such as shape, dimensions, weight,
      scored lines, coatings, etc.) to profile the most suitable forms of tablets for
      automated dose dispensing systems. The relationship between the risk of errors in
      dose dispensing and tablet characteristics were visualized by creating a
      principal component analysis (PCA) model for the outcome of dispensed tablets.
      The two most common process-induced failures identified in the multi-dose
      dispensing are predisposal of tablet defects and unexpected product transitions
      in the medication cassette (dose dispensing error). The tablet defects are
      product-dependent failures, while the tablet transitions are dependent on
      automated multi-dose dispensing systems used. The occurrence of tablet defects is
      approximately twice as common as tablet transitions. Optimal tablet preparation
      for the high-speed multi-dose dispensing would be a round-shaped, relatively
      small/middle-sized, film-coated tablet without any scored line. Commercial tablet
      products can be profiled and classified based on their suitability to a high
      speed multi-dose dispensing process.

PMID- 22458300
TI  - Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a
      population-based case-control study.
AB  - OBJECTIVES: To explore the risk of developing Alzheimer's disease (AD) in
      individuals with diabetes mellitus treated with metformin or other antidiabetic
      drugs. DESIGN: Case-control study. SETTING: The United Kingdom-based General
      Practice Research Database (GPRD), a well-established primary care database.
      PARTICIPANTS: Seven thousand eighty-six individuals aged 65 and older with an
      incident diagnosis of AD identified between 1998 and 2008 and the same number of
      matched controls without dementia. Matching criteria were age, sex, general
      practice, calendar time, and years of history in the database. MEASUREMENTS:
      Comparison of previous use of metformin or other antidiabetic drugs between cases
      and controls and calculation of corresponding odds ratios (ORs) with 95%
      confidence intervals (CIs), using conditional logistic regression. Risk estimates
      were stratified according to duration of use and adjusted for potential
      confounders. RESULTS: As compared with nonusers, long-term users of 60 or more
      metformin prescriptions were at greater risk of developing AD (adjusted OR (AOR)
      = 1.71, 95% CI = 1.12-2.60), but there was no consistent trend with increasing
      number of prescriptions. Long-term use of other antidiabetic drugs such as
      sulfonylureas (AOR = 1.01, 95% CI = 0.72-1.42), thiazolidinediones (AOR = 0.87,
      95% CI = 0.31-2.40), or insulin (AOR = 1.01, 95% CI = 0.58-1.73) was not related
      to an altered risk of developing AD. CONCLUSION: Long-term use of sulfonylureas,
      thiazolidinediones, or insulin was not associated with an altered risk of
      developing AD. There was a suggestion of a slightly higher risk of AD in long
      term users of metformin.

PMID- 22458301
TI  - Tobacco and alcohol-related interventions for people with mild/moderate
      intellectual disabilities: a systematic review of the literature.
AB  - BACKGROUND: The behavioural determinants of health among people with
      mild/moderate intellectual disabilities (ID) are of increasing concern. With the
      closure of long-stay institutions, more people with ID are living in the
      community. As they lead more ordinary and less restricted lives, people with ID
      may be exposed to social and environmental pressures that encourage them to adopt
      behaviours that impact negatively on their health. Levels of smoking and alcohol
      consumption in this client group are of particular concern. METHODS: We undertook
      a mixed method review of the literature, aiming to assess the Feasibility,
      Appropriateness, Meaningfulness and Effectiveness (FAME) of interventions
      designed to address the use of tobacco and/or alcohol in people with
      mild/moderate ID. Key electronic databases were searched (e.g., Medline, Cochrane
      Register of Controlled Trials, PsycINFO) from 1996 to 2011. The search was
      developed using appropriate subject headings and key words (e.g., intellectual
      disability, tobacco use, alcohol drinking, health promotion). On completion of
      the database searches, inclusion/exclusion criteria, based on an adaptation of
      the PICO framework (Population, Intervention, Comparison, Outcomes), were
      applied. Methodological quality was assessed using a seven-point rating scale.
      RESULTS: Database searches identified 501 unique records, of which nine satisfied
      the inclusion criteria. Four focused on tobacco, three on alcohol and two on both
      tobacco and alcohol. Located in the U.K., the U.S.A. and Australia, the studies
      aimed to increase knowledge levels and/or change behaviour (e.g., to encourage
      smoking cessation). One was a randomised controlled trial, one a quasi-experiment
      and the others were before and after studies and/or case studies. Methodological
      quality was poor or moderate. The combined studies had a sample size of 341, with
      ages ranging from 14 to 54 years. The interventions were delivered by
      professionals (e.g., in health, social care, education) during sessions that
      spanned a period of three weeks to one academic year. The studies highlighted a
      number of important issues linked to the appropriateness of interventions for
      this client group (e.g., use of pictures, quizzes, role play, incentives);
      however, in the majority of cases the interventions appeared to lack a
      theoretical framework (e.g., behaviour change theory). The appropriateness of the
      outcome measures for use with this client group was not tested. One study
      discussed feasibility (teachers delivering lessons on alcohol and tobacco) and
      only one was informative in terms of effectiveness, i.e., increasing knowledge of
      the health and social dangers of smoking and excessive alcohol consumption.
      CONCLUSIONS: This review is the first to systematically collate evidence on
      tobacco and alcohol-related interventions for people with ID. While there is
      currently little evidence to guide practice, the review delivers clear insights
      for the development of interventions and presents a strong case for more robust
      research methods. In particular there is a need to test the effectiveness of
      interventions in large-scale, well-designed trials and to ensure that outcome
      measures are developed/tailored appropriately for this client group.

PMID- 22458302
TI  - The evolution of orgasmic pain (dysorgasmia) following radical prostatectomy.
AB  - INTRODUCTION: It is recognized that some patients experience painful orgasms
      known as dysorgasmia after radical prostatectomy (RP). This problem poses a
      barrier to satisfactory sexual relations for some couples. However, the natural
      history of this condition remains unknown. AIM: To assess the evolution of
      dysorgasmia in patients who underwent RP. METHODS: The study population included
      men who had been seen initially within 6 months after RP and complained of
      postoperative dysorgasmia and opted for no medical therapy with postoperative
      follow-up at least 24 months, and were seen at least twice over 2 years. MAIN
      OUTCOME MEASURES: A proprietary dysorgasmia frequency scale and visual analog
      scale (VAS) for pain were used at each visit. RESULTS: Data from 702 patients who
      had RP and presented for sexual function evaluation between 2002 and 2008 were
      prospectively collected and analyzed at Memorial Sloan-Kettering Cancer Center.
      Of the 702 patients, 84 (12%) complained of dysorgasmia. Mean patient age was 64
      +/- 16 years. Mean time interval since RP to initial sexual medicine interview
      was 2.2 +/- 3.2 months. Mean number of visits was 4 +/- 1.4. For the 84 patients
      who had dysorgasmia, mean dysorgasmia frequency and VAS score for pain at initial
      interview were 3.9 and 4.1, respectively. At 24 months, a statistically
      significant decrease in symptoms occurred, with 72%, 26%, and 7% of patients
      still complaining of pain at 12, 18, and 24 months, respectively. At 6 months,
      26% of patients had a VAS score >=6/10 and at 24 months this figure was 16%.
      CONCLUSIONS: Our data provide evidence that dysorgasmia decreases in frequency
      and degree over time after RP. These data are in support of a surveillance
      strategy for all but the most bothered patients with dysorgasmia after RP.

PMID- 22458303
TI  - Liminality as a framework for understanding the experience of cancer
      survivorship: a literature review.
AB  - AIMS: To report a narrative review of literature that drew on the concept of
      liminality as a framework for understanding the cancer experience. In doing so,
      we explored the utility of liminality for guiding research on experiences of
      cancer survivorship. BACKGROUND: The 'rites of passage' model uses the concept of
      liminality to explore transition. Taking cancer survivorship as a process,
      liminality may facilitate our understanding of this phenomenon. DATA SOURCES:
      Searches of Medline, PsycInfo, British Nursing Index, Cinahl, ASSIA, Web of
      Science, Cochrane Library and British Library databases were conducted, covering
      1985-2011. Search terms were cancer and liminal* or rite* of passage. DESIGN: A
      narrative review, using a textual narrative approach, was undertaken to provide a
      comprehensive overview of the topic. REVIEW METHODS: Studies were arranged into
      groups according to the stage of the cancer trajectory on which they focused.
      Findings from each study were presented to highlight facets of the liminal
      experience at each stage. RESULTS: Ten studies were included for review.
      Liminality depicts the ambiguity and uncertainty often experienced by people
      affected by cancer. Although liminality appears useful for understanding
      experiences of cancer risk, diagnosis, treatment and the period following active
      treatment, little research has explored the concept with respect to long-term
      survivorship. CONCLUSION: Gaps in current evidence highlight the need for
      additional research to ascertain the utility of liminality for understanding
      experiences of long-term survivorship. Research exploring the personal and social
      implications of living a liminal life, at all stages of the cancer trajectory, is
      also warranted.

PMID- 22458304
TI  - Conception rate, uterine infection and embryo quality after artificial
      insemination and natural breeding with a stallion carrier of Pseudomonas
      aeruginosa: a case report.
AB  - BACKGROUND: Pseudomonas aeruginosa may cause venereal disease and infertility in
      horses. A Pseudomonas aeruginosa - carrier stallion, often unresponsive to
      artificial vagina collection, was used to naturally breed mares. Semen collected
      from the same stallion was also used to perform artificial inseminations.
      Pregnancy rates, embryo quality and incidence of uterine infection were compared
      between inseminated or naturally-bred mares. METHODS: P. aeruginosa was isolated
      from swabbing of the penis, prepuce and distal urethra of the stallion. Before
      being bred or inseminated, clitoral/vestibular samples were collected from all
      mares, and cultured for isolation of P. aeruginosa. At the first observed estrus,
      endometrial swabs were also collected. All mares subjected to natural mating (NS)
      were re-evaluated for P.aeruginosa by culture of clitoral and endometrial swabs.
      Artificial inseminations (AI) were performed either with fresh-extended semen (11
      AI/7 mares) or frozen semen (10 AI/7 mares). The stallion was also used to breed
      3 mares (4 services). For embryo collection, 2 mares were inseminated with fresh
      extended semen (1 AI/mare), and 2 additional mares were inseminated with frozen
      semen (2 AI/mare). Two mares were naturally-bred with a total of 9 services, for
      embryo collection. All mares were examined after AI or natural service (NS), for
      uterine pathologies. Embryo recoveries were attempted passing a catheter with
      inflatable cuff connected to a sterile flexible 2-way flushing catheter, through
      the cervix. Flushed media was recovered into an Em-Con filter, and embryos
      searched using a stereoscope. Embryos were graded from 1 (excellent) to 4
      (degenerated/dead). RESULTS: Pregnancy rates obtained after NS was 50% per cycle.
      However, more than half of the NS resulted in uterine disease, while uterine
      pathology was seen only in 22% of the time following AI. Half of the mares bred
      by NS got positive to P. aeruginosa. Percentage of embryo recovery rates was
      identical after AI or NS (66.7%). The 4 embryos recovered after AI were
      classified as Grade 1, while after NS only 2 out of the 6 recovered embryos were
      Grade 1. CONCLUSION: a) there was no evidence of reduced fertilization after AI
      or NS, b) a numerically higher incidence of uterine disease was noticed after NS,
      c) venereal transmission of P. aeruginosa after NS was confirmed, d) a lower
      percentage of G1 embryos may be obtained after NS. Overall, the data supports the
      indication for P. aeruginosa-carrier stallions to be bred by AI rather than by
      NS, and raises the possibility that P. aeruginosa may affect embryo quality.

PMID- 22458305
TI  - Medication and supplement use for managing joint symptoms among patients with
      knee and hip osteoarthritis: a cross-sectional study.
AB  - BACKGROUND: The purpose was to determine the professionally-guided and self
      guided medication and supplement use for joint symptom management among patients
      with knee and/or hip osteoarthritis (OA) in an urban hospital-based outpatient
      orthopedic practice. METHODS: The study design was cross-sectional. Patients
      diagnosed by radiographs and clinical symptoms with knee and/or hip OA were
      recruited from an inner-city hospital-based outpatient orthopaedic office. A
      total of 184 patients were queried for their participation. Four investigator
      generated, interview-based questionnaires were used. Sampling error was +/-7.84%.
      Logistic regression models and Fisher Exact Tests were performed to determine
      factors that may be associated with negative behaviors related to medication or
      supplement use (e.g., reporting medication as ineffective, using multiple
      medications in the same day to manage symptoms). Odds ratios (OR) and 95%
      confidence intervals (CI) were calculated for significant findings. RESULTS:
      Among the 162 participants, a majority reported professionally-guided
      recommendations and over 40% reported at least one self-guided intervention. 37
      participants reported dual-use during the same day, and among those,15 reported
      dual-use at the same time. Among participants taking multiple interventions in
      the same day, 40.5% reported using prescription and over-the-counter medications.
      Use of multiple medications or supplements in one day was more common among
      participants who reported OA at multiple joints (OR [95% CI]=2.48 [1.03 to 5.96])
      but less common among participants who did not complete high school (OR [95%
      CI]=0.26 [0.08 to 0.83]). Of the 15 participants who reported dual-use at the
      same time, 11 were professionally-guided, 5 were professional and self-guided,
      and 1 was solely self-guided. Overall, 28% of participants reported their
      intervention as ineffective, sought an alternative method to achieve symptomatic
      relief, or were prescribed a stronger medication. Participants who reported not
      always taking their medication consistently for 2 weeks were more likely to
      report their medication as ineffective (OR [95% CI]=2.87 [1.19 to 6.92]).
      CONCLUSIONS: Both professional and self-guided medications and supplements are
      used by inner city OA patients to manage their joint symptoms. It is important
      for clinicians to discuss with these patients how to effectively manage multiple
      joint symptoms, the importance of taking medications as prescribed, and what they
      should if they believe a treatment is ineffective or their medication runs out.

PMID- 22458306
TI  - Peroxisome deficiency but not the defect in ether lipid synthesis causes
      activation of the innate immune system and axonal loss in the central nervous
      system.
AB  - BACKGROUND: Mice with peroxisome deficiency in neural cells (Nestin-Pex5-/-)
      develop a neurodegenerative phenotype leading to motor and cognitive disabilities
      and early death. Major pathologies at the end stage of disease include severe
      demyelination, axonal degeneration and neuroinflammation. We now investigated the
      onset and progression of these pathological processes, and their potential
      interrelationship. In addition, the putative role of oxidative stress, the impact
      of plasmalogen depletion on the neurodegenerative phenotype, and the consequences
      of peroxisome elimination in the postnatal period were studied. METHODS:
      Immunohistochemistry in association with gene expression analysis was performed
      on Nestin-Pex5-/- mice to document demyelination, axonal damage and
      neuroinflammation. Also Gnpat-/- mice, with selective plasmalogen deficiency and
      CMV-Tx-Pex5-/- mice, with tamoxifen induced generalized loss of peroxisomes were
      analysed. RESULTS: Activation of the innate immune system is a very early event
      in the pathological process in Nestin-Pex5-/- mice which evolves in chronic
      neuroinflammation. The complement factor C1q, one of the earliest up regulated
      transcripts, was expressed on neurons and oligodendrocytes but not on microglia.
      Transcripts of other pro- and anti-inflammatory genes and markers of phagocytotic
      activity were already significantly induced before detecting pathologies with
      immunofluorescent staining. Demyelination, macrophage activity and axonal loss co
      occurred throughout the brain. As in patients with mild peroxisome biogenesis
      disorders who develop regressive changes, demyelination in cerebellum and brain
      stem preceded major myelin loss in corpus callosum of both Nestin-Pex5-/- and CMV
      Tx-Pex5-/- mice. These lesions were not accompanied by generalized oxidative
      stress throughout the brain. Although Gnpat-/- mice displayed dysmyelination and
      Purkinje cell axon damage in cerebellum, confirming previous observations, no
      signs of inflammation or demyelination aggravating with age were observed.
      CONCLUSIONS: Peroxisome inactivity triggers a fast neuroinflammatory reaction,
      which is not solely due to the depletion of plasmalogens. In association with
      myelin abnormalities this causes axon damage and loss.

PMID- 22458307
TI  - Friedel-Crafts amidoalkylation via thermolysis and oxidative photocatalysis.
AB  - Friedel-Crafts amidoalkylation was achieved by oxidation of dialkylamides using
      persulfate (S(2)O(8)(2-)) in the presence of the visible light catalyst,
      Ru(bpy)(3)Cl(2), at room temperature, via a reactive N-acyliminium intermediate.
      Alternatively, mild heating of the dialkylamides and persulfate afforded a metal
      and Lewis acid-free Friedel-Crafts amidoalkylation. Alcohols and electron-rich
      arenes served as effective nucleophiles, forming new C-O or C-C bonds. In
      general, photocatalysis provided higher yields and better selectivities.

PMID- 22458309
TI  - Synergetic effect of MoS2 and graphene as cocatalysts for enhanced photocatalytic
      H2 production activity of TiO2 nanoparticles.
AB  - The production of H(2) by photocatalytic water splitting has attracted a lot
      attention as a clean and renewable solar H(2) generation system. Despite
      tremendous efforts, the present great challenge in materials science is to
      develop highly active photocatalysts for splitting of water at low cost. Here we
      report a new composite material consisting of TiO(2) nanocrystals grown in the
      presence of a layered MoS(2)/graphene hybrid as a high-performance photocatalyst
      for H(2) evolution. This composite material was prepared by a two-step simple
      hydrothermal process using sodium molybdate, thiourea, and graphene oxide as
      precursors of the MoS(2)/graphene hybrid and tetrabutylorthotitanate as the
      titanium precursor. Even without a noble-metal cocatalyst, the
      TiO(2)/MoS(2)/graphene composite reaches a high H(2) production rate of 165.3
      MUmol h(-1) when the content of the MoS(2)/graphene cocatalyst is 0.5 wt % and
      the content of graphene in this cocatalyst is 5.0 wt %, and the apparent quantum
      efficiency reaches 9.7% at 365 nm. This unusual photocatalytic activity arises
      from the positive synergetic effect between the MoS(2) and graphene components in
      this hybrid cocatalyst, which serve as an electron collector and a source of
      active adsorption sites, respectively. This study presents an inexpensive
      photocatalyst for energy conversion to achieve highly efficient H(2) evolution
      without noble metals.

PMID- 22458308
TI  - Childhood body mass index trajectories: modeling, characterizing, pairwise
      correlations and socio-demographic predictors of trajectory characteristics.
AB  - BACKGROUND: Modeling childhood body mass index (BMI) trajectories, versus
      estimating change in BMI between specific ages, may improve prediction of later
      body-size-related outcomes. Prior studies of BMI trajectories are limited by
      restricted age periods and insufficient use of trajectory information. METHODS:
      Among 3,289 children seen at 81,550 pediatric well-child visits from infancy to
      18 years between 1980 and 2008, we fit individual BMI trajectories using mixed
      effect models with fractional polynomial functions. From each child's fitted
      trajectory, we estimated age and BMI at infancy peak and adiposity rebound, and
      velocity and area under curve between 1 week, infancy peak, adiposity rebound,
      and 18 years. RESULTS: Among boys, mean (SD) ages at infancy BMI peak and
      adiposity rebound were 7.2 (0.9) and 49.2 (11.9) months, respectively. Among
      girls, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.4 (1.1)
      and 46.8 (11.0) months, respectively. Ages at infancy peak and adiposity rebound
      were weakly inversely correlated (r = -0.09). BMI at infancy peak and adiposity
      rebound were positively correlated (r = 0.76). Blacks had earlier adiposity
      rebound and greater velocity from adiposity rebound to 18 years of age than
      whites. Higher birth weight z-score predicted earlier adiposity rebound and
      higher BMI at infancy peak and adiposity rebound. BMI trajectories did not differ
      by birth year or type of health insurance, after adjusting for other socio
      demographics and birth weight z-score. CONCLUSIONS: Childhood BMI trajectory
      characteristics are informative in describing childhood body mass changes and can
      be estimated conveniently. Future research should evaluate associations of these
      novel BMI trajectory characteristics with adult outcomes.

PMID- 22458310
TI  - Theoretical study on the transition-metal oxoboryl complex: M-BO bonding nature,
      mechanism of the formation reaction, and prediction of a new oxoboryl complex.
AB  - The Pt-BO bonding nature and the formation reaction of the experimentally
      reported platinum(II) oxoboryl complex, simplified to PtBr(BO)(PMe(3))(2), were
      theoretically investigated with the density functional theory method. The BO(-)
      ligand was quantitatively demonstrated to have extremely strong sigma-donation
      but very weak d(pi)-electron-accepting abilities. Therefore, it exhibits a strong
      trans influence. The formation reaction occurs through a four-center transition
      state, in which the B(delta+)-Br(delta-) polarization and the Br -> Si and O
      p(pi) -> B p(pi) charge-transfer interactions play key roles. The Gibbs
      activation energy (DeltaG degrees (++)) and Gibbs reaction energy (DeltaG degrees
      ) of the formation reaction are 32.2 and -6.1 kcal/mol, respectively. The
      electron-donating bulky phosphine ligand is found to be favorable for lowering
      both DeltaG degrees (++) and DeltaG degrees . In addition, the metal effect is
      examined with the nickel and palladium analogues and
      MBrCl[BBr(OSiMe(3))](CO)(PR(3))(2) (M = Ir and Rh). By a comparison of the DeltaG
      degrees (++) and DeltaG degrees  values, the M-BO (M = Ni, Pd, Ir, and Rh)
      bonding nature, and the interaction energy between [MBrCl(CO)(PR(3))(2)](+) and
      BO(-) with those of the platinum system, MBrCl(BO)(CO)(PR(3))(2) (M = Ir and Rh)
      is predicted to be a good candidate for a stable oxoboryl complex.

PMID- 22458311
TI  - Farmers' concerns: a qualitative assessment to plan rural medical education.
AB  - CONTEXT: Limited research suggests that translational approaches are needed to
      decrease the distance, physical and cultural, between farmers and health care.
      PURPOSE: This study seeks to identify special concerns of farmers in Alabama and
      explore the need for a medical education program tailored to prepare physicians
      to address those concerns. METHODS: We conducted 2 focus groups with 20 farmers
      from diverse communities, backgrounds, and farming operations. The sessions were
      audio-recorded, transcribed, coded, and analyzed for determined patterns.
      FINDINGS: The following categories were developed as areas of importance to
      farmers: the need for physicians to understand the culture of farming,
      occupational exposures in farming, and recommendations for improving the health
      of farmers. CONCLUSION: Findings suggest that to adequately serve farmers,
      medical students interested in entering practice in rural areas should have or
      develop a relevant and adequate understanding of farming practices.

PMID- 22458312
TI  - Teaching and learning resilience: building adaptive capacity for rural practice.
      A report and subsequent analysis of a workshop conducted at the Rural Medical
      Educators Conference, Savannah, Georgia, May 18, 2010.
AB  - PURPOSE: Resilience, the capacity to endure and overcome hardship, has been
      suggested as a basic competency for rural medical practice. Unfortunately for
      physician educators, the medical education literature offers only limited
      guidance for nurturing this adaptive capacity. We describe the process and
      subsequent analysis of a daylong curriculum development workshop conducted at the
      annual meeting of Rural Medical Educators in 2010. METHODS: Fifty administrator,
      faculty and student attendees reflected individually and worked in groups to
      construct key curricular components and modalities for teaching this competency.
      Prior to the meeting, participants were asked to submit a personal story about
      resilience. The 22 narratives received were distributed across 8 groups and
      provided the grist for the small group discussions, in which each group
      identified key concepts for teaching and learning about resilience, constructed a
      concept map, and developed a curriculum that was presented to all session
      participants. Concept maps, curriculum outlines and notes taken during the
      presentations were analyzed using content analysis techniques. FINDINGS: Data
      highlight the importance of (1) embracing hardship as an opportunity for growth,
      (2) viewing resilience as both an individual and community property, (3) pursuing
      adaptability more than hardiness, and (4) setting a lifelong pattern of learning
      this competency in practice. Specific teaching modalities are suggested including
      individual reflective time and group activities. CONCLUSIONS: To our knowledge
      this represents a first effort to define and develop a medical curriculum for
      teaching resiliency in rural predoctoral and residency education.

PMID- 22458314
TI  - Orthopedic surgery in rural American hospitals: a survey of rural hospital
      administrators.
AB  - Rural American residents prefer to receive their medical care locally. Lack of
      specific medical services in the local community necessitates travel to a larger
      center which is less favorable. This study was done to identify how rural
      hospitals choose to provide orthopedic surgical services to their communities.
      METHODS: All hospitals in 5 states located in communities that met the criteria
      for a rural town according to the Rural Urban Commuting Area codes were included.
      A survey with topics including community and hospital demographics, orthopedic
      surgical workforce and demand, surgical services, and the perceived benefit of
      orthopedic services was sent to the hospital administrators. RESULTS: Of the 223
      rural hospitals surveyed, 145 completed the survey. Of those completing the
      survey, 30% had at least one full-time orthopedic surgeon, 25% did not provide
      any orthopedic surgical services, 65% never had an orthopedic surgeon on ER call,
      33% were recruiting an orthopedic surgeon, 52% stated that it is more difficult
      to recruit an orthopedic surgeon vs a general surgeon, and 71% of the
      administrators acknowledged a need for additional orthopedic surgical services in
      their community. For those hospitals that did not have a full-time orthopedic
      surgeon, members of those communities traveled a mean distance of 55 miles for
      emergency orthopedic surgical care as reported by the hospital administrators.
      CONCLUSIONS: There are many rural communities that have limited access to
      orthopedic surgical services. While many of the rural hospital administrators
      feel that there is a need for additional orthopedic surgical services in their
      communities, it is difficult to recruit orthopedic surgeons to these areas.

PMID- 22458313
TI  - Admission factors predicting family medicine specialty choice: a literature
      review and exploratory study among students in the Rural Medical Scholars
      Program.
AB  - PURPOSE: The Rural Medical Scholars Program (RMSP) was created to increase
      production of rural family physicians in Alabama. Literature review reveals
      reasons medical students choose careers in family medicine, and these reasons can
      be categorized into domains that medical schools can address through admission,
      curriculum, and structural interventions. We examine whether admission factors
      can predict family medicine specialty choice among students recruited from rural
      Alabama. METHODS: We developed a questionnaire to study the ability of admission
      factors to predict family medicine specialty choice among Rural Medical Scholars
      (RMS). Eighty RMS graduates were surveyed by mail and 64 (80%) responded.
      FINDINGS: Student characteristics of humanitarian outlook with commitment to
      rural or underserved populations, family medicine decision or intention made
      before or at medical school admission, and community influence were positive
      associations with RMS choosing family medicine residencies; shadowing in an urban
      hospital was a negative association. CONCLUSIONS: Statements of interest,
      intentions, plans, and decisions regarding family medicine should be elicited at
      the time of RMSP admission interview. Strong attachment to home community and
      commitment to serving and living in a rural area are also important. Students
      whose introduction to medicine was informed through shadowing or observing in
      urban hospitals should be considered less likely to become family physicians.
      Larger sample size studies are needed to assess the role of gender, race, marital
      status, size of rural town, and MCAT score of candidates in affecting residency
      choices of students selected for this rural medical education track.

PMID- 22458315
TI  - Cognitive appraisals of specialty mental health services and their relation to
      mental health service utilization in the rural population.
AB  - PURPOSE: Rural individuals utilize specialty mental health services (eg,
      psychiatrists, psychologists, counselors, and social workers) at lower rates than
      their urban counterparts. This study explores whether cognitive appraisals (ie,
      individual perceptions of need for services, outcome expectancies, and value of a
      positive therapeutic outcome) of help-seeking for depression symptoms are related
      to the utilization of specialty mental health services in a rural sample.
      METHODS: Demographic and environmental characteristics, cultural barriers,
      cognitive appraisals, and depression symptoms were assessed in one model
      predicting specialty mental health service utilization (MHSU) in a rural sample.
      Three hypotheses were proposed: (1) a higher number of environmental barriers
      (eg, lack of insurance or transportation) would predict lower specialty mental
      health service utilization; (2) an increase in cultural barriers (stigma,
      stoicism, and lack of anonymity) would predict lower specialty mental health
      utilization; and (3) higher cognitive appraisals of mental health services would
      predict specialty mental health care utilization beyond the predictive capacities
      of psychiatric symptoms, demographic variables, environmental barriers, and
      cultural barriers. FINDINGS: Current depression symptoms significantly predicted
      lifetime specialty mental health service utilization. Hypotheses 1 and 2 were not
      supported: more environmental barriers predicted higher levels of specialty MHSU
      while cultural barriers did not predict specialty mental health service
      utilization. Hypothesis 3 was supported: cognitive appraisals significantly
      predicted specialty mental health service utilization. CONCLUSIONS: It will be
      important to target perceptions and attitudes about mental health services to
      reduce disparities in specialty MHSU for the rural population.

PMID- 22458316
TI  - Emergency department reliance among rural children in Medicaid in New York State.
AB  - PURPOSE: This study examines variation in emergency department reliance (EDR)
      between rural and metro pediatric Medicaid patients in New York State for
      noninjury, nonpoisoning primary diagnoses and seeks to determine the relationship
      between receipt of preventive care and the likelihood of EDR. METHODS:
      Rural/urban designations were based on Urban Influence Codes established by the
      United States Department of Agriculture (USDA). Healthcare Effectiveness Data and
      Information Set (HEDIS((r))) well-visit measures were calculated using 2008
      Medicaid claims and encounter data. Well-child numerator status and location of
      residence variables were then entered as independent variables in multivariate
      logistic regression models. Models controlled for the effects of Medicaid
      financing system (fee-for-service vs managed care), Medicaid aid type,
      race/ethnicity, gender, and 2008 clinical risk group category. FINDINGS: The
      likelihood of EDR was higher in all age categories for rural compared to metro
      residing Medicaid children in New York State. Meeting HEDIS well-child criteria
      was protective against emergency department (ED) reliance in the adolescence age
      group (OR = 0.84). CONCLUSION: ED reliance is associated with rural residence.
      Increased access to primary and specialty care in rural settings could help
      reduce EDR, particularly among rural adolescents.

PMID- 22458317
TI  - Birth outcomes across three rural-urban typologies in the Finger Lakes region of
      New York.
AB  - PURPOSE: The study is a descriptive, population-based analysis of birth outcomes
      in the New York State Finger Lakes region designed to determine whether perinatal
      outcomes differed across 3 rural typologies. METHODS: Hospital birth data for the
      Finger Lakes region from 2006 to 2007 were used to identify births classified as
      low birthweight (LBW), small for gestational age (SGA), and preterm delivery
      (PTD). Maternal residences were defined using 3 existing ZIP code-level rural
      urban typologies: Census Bureau ZIP codes, Rural-Urban Commuting Area codes, and
      Primary Service Areas. Within each typology, rural maternal characteristics and
      birth outcomes were compared to those in urban areas using multivariable logistic
      regression models. FINDINGS: In bivariate analyses, rurality was associated with
      LBW and SGA for all typologies, whereas PTD was associated with residence in the
      Census Bureau typology only. After controlling for demographic characteristics,
      births to mothers in the most rural level of the Census Bureau typology and to
      all rural mothers in the Rural-Urban Commuting Area (RUCA) and Primary Service
      Area typologies were more likely to be LBW and PTD. SGA was not consistently
      associated with residence across typologies. CONCLUSIONS: The typologies produced
      similar results for these outcomes, although effects were of greater magnitude in
      the RUCA and Primary Service Area typologies than in the Census Bureau typology.
      Comparison across typologies can have practical implications for researchers and
      policy makers interested in understanding the dynamics of rurality and birth
      outcomes in their regions.

PMID- 22458318
TI  - White infant mortality in Appalachian states, 1976-1980 and 1996-2000: changing
      patterns and persistent disparities.
AB  - PURPOSE: Appalachian counties have historically had elevated infant mortality
      rates. Changes in infant mortality disparities over time in Appalachia are not
      well-understood. This study explores spatial inequalities in white infant
      mortality rates over time in the 13 Appalachian states, comparing counties in
      Appalachia with non-Appalachian counties. METHODS: Data are analyzed for 1,100
      counties in 13 Appalachian states that include 420 counties designated as
      Appalachian by the Appalachian Regional Commission. Area Resource File data for
      1976-1980 and 1996-2000 provide county- and city-level infant mortality rates,
      poverty rates, rural-urban continuum codes, and numbers of physicians per 1,000
      residents. Multiple regression analyses evaluate whether Appalachian counties are
      significantly associated with elevated white infant mortality in each time
      period, accounting for covariates. FINDINGS: White infant mortality rates
      decreased substantially in all sub-regions over the last 2 decades; however,
      disparities in infant mortality did not diminish in Appalachian counties compared
      to non-Appalachian counties. After accounting for poverty, rural/urban status,
      and health care resources, Appalachian counties were significantly associated
      with comparatively higher infant mortality during the late 1970s but not in the
      late 1990s. At the more recent time point, higher poverty rates, residence in
      more rural areas, and lower physician density were associated with greater infant
      mortality risk. CONCLUSION: Appalachian counties continue to experience
      relatively elevated infant mortality rates. Poverty and rurality remain important
      dimensions of health service need in Appalachia.

PMID- 22458319
TI  - Self-rated health and the "first move" around retirement: a longitudinal study of
      older Americans.
AB  - PURPOSE: I examine whether less favorable self-rated health raises the risk of
      outmigration more for young-old adults (aged 53-63 at the start of the 10-year
      longitudinal study in 1994) in nonmetro than metro counties and increases the
      odds that both groups of outmigrants will choose metro over nonmetro
      destinations. Finally, I examine whether nonmetro outmigrants are more likely
      than metro outmigrants to cite a health concern or a desire to get closer to
      relatives or friends as a reason for the migration. METHODS: I use the Health and
      Retirement Study (HRS) to track the main residences of nonmetro and metro older
      adults from 1994-2003. With a discrete-time Event History Analysis, I assess the
      joint effects of nonmetro/metro residence in 1994 and self-rated health (updated
      at each biennial wave) upon the risk of a first migration. Those who migrated
      were asked to recall why. FINDINGS: At worse levels of self-rated health, the
      odds of remaining in a nonmetro county of residence drop in favor of migrating to
      another nonmetro county. Among migrants, the worse the self-rated health, the
      higher the odds of within-type migration (nonmetro-nonmetro and metro-metro) over
      cross-type migration (nonmetro-metro and metro-nonmetro). The percentages of
      migrants citing a health concern or a desire to live closer to relatives or
      friends as a reason for migration do not differ by county type of origin.
      CONCLUSIONS: An implication for rural health policy is that young-old adults with
      worse self-rated health tend to remain in nonmetro areas, even when they migrate.

PMID- 22458320
TI  - The effect of increased travel reimbursement rates on health care utilization in
      the VA.
AB  - PURPOSE: The reimbursement rate that eligible veterans receive for travel to
      Department of Veterans Affairs (VA) facilities increased from 11 to 28.5 cents
      per mile on February 1, 2008. We examined the effect of this policy change on
      utilization of outpatient, inpatient, and pharmacy services, stratifying veterans
      based on distance from a VA facility. METHODS: We compared health care
      utilization and costs on a sample of VA patients in the 10.5 months before the
      reimbursement rate increase and the 10.5 months after the reimbursement rate
      increase. Using a difference-in-difference technique, we ran multivariable
      logistic and count regressions for utilization and generalized linear models
      (GLM) for cost outcomes. Regressions were stratified based on urban and rural
      residence, as well as by distance thresholds. FINDINGS: Our cohort contained
      250,958 veterans, 76.7% (n = 192,559) of whom were eligible to receive a travel
      reimbursement. After the reimbursement rate increase, eligible veterans at all
      distances were 6.8% more likely to have an outpatient encounter and had 2.6% more
      outpatient encounters in the VA compared to those not eligible for the
      reimbursement (P< .001). Similar results were found for prescription fills at all
      distances, but inpatient encounters remained generally unaffected. CONCLUSIONS:
      Our results suggest that this policy change was successful in increasing access
      to VA care for patients regardless of location of residence.

PMID- 22458321
TI  - Alcohol consumption among urban, suburban, and rural Veterans Affairs
      outpatients.
AB  - PURPOSE: United States rural residents tend toward poorer health than urban
      residents. Although alcohol use is associated with multiple medical conditions
      and can be reduced via brief primary care-based interventions, it is unknown
      whether alcohol consumption differs by rurality among primary care patients. We
      sought to describe alcohol consumption among urban, suburban, and rural Veterans
      Affairs (VA) outpatients. METHODS: Outpatients from 7 VA facilities responded to
      mailed surveys that included the validated Alcohol Use Disorders Identification
      Test Consumption (AUDIT-C) screening questionnaire. The ZIP code approximation of
      the US Department of Agriculture's rural-urban commuting area (RUCA) codes
      classified participants into urban, suburban, and rural areas. For each area,
      adjusted logistic regression models estimated the prevalence of past-year
      abstinence among all participants and unhealthy alcohol use (AUDIT-C >= 3 for
      women and >= 4 for men) among drinkers. FINDINGS: Among 33,883 outpatients,
      14,967 (44%) reported abstinence. Among 18,916 drinkers, 8,524 (45%) screened
      positive for unhealthy alcohol use. The adjusted prevalence of abstinence was
      lowest in urban residents (43%, 95% CI 42%-43%) with significantly higher rates
      in both suburban and rural residents [45% (44%-46%) and 46% (45%-47%),
      respectively]. No significant differences were observed in the adjusted
      prevalence of unhealthy alcohol use among drinkers. CONCLUSIONS: Abstinence is
      slightly more common among rural and suburban than urban VA outpatients, but
      unhealthy alcohol use does not vary by rurality. As the VA and other health
      systems implement evidence-based care for unhealthy alcohol use, more research is
      needed to identify whether preventive strategies targeted to high-risk areas are
      needed.

PMID- 22458322
TI  - Layer thickness of hydrophobin films leads to oscillation in wettability.
AB  - In nanobiotechnology, the properties of surfaces are often key to sensor
      applications. If analytes possess a low tolerance or affinity regarding the
      sensory substrate (surface), then the setup of mediators may be indicated.
      Hydrophobins enable biocompatible surface functionalization without significant
      restrictions of the physicochemical substrate properties. Because of the
      imperfect formation of hydrophobin films, a high variation in surface properties
      is observed. In this study, we report on the relation between the film thickness
      of hydrophobin-coated solid surfaces and their wettability. We found that the
      wettability of protein-coated surfaces strictly depends on the amount of adsorbed
      protein, as reflected in an oscillation of the contact angles of hydrophobin
      coated silicon wafers. Fusion proteins of Ccg2 and HFBI, representatives of class
      I and II hydrophobins, document the influence of fused peptide tags on the
      wettability. The orientation of the first crystal nuclei plays a decisive role in
      the formation of the growing hydrophobin layers. Here, a simple method of
      deducing the film thickness of hydrophobin assemblies on solid surfaces is
      presented. The determination of the static contact angle allows the prediction of
      which part of the protein is exposed to possible analytes.

PMID- 22458323
TI  - Effects of silver nanoparticles on rat hepatic cytochrome P450 enzyme activity.
AB  - Silver nanoparticles (AgNPs) are increasingly used in various products and
      consequentially the potential adverse effects associated with exposure to them
      are of concern. This study investigated the effects of AgNPs on the hepatic drug
      metabolizing enzymes of the cytochrome P450 (CYP) families 1, 2 and 3, using both
      in vitro and in vivo biological assays. AgNPs were orally administered to Sprague
      Dawley rats at various concentrations (0-1000 mg/kg body weight/day) for 2 weeks.
      No effect was found on the plasma levels of ALT, AST and ALP in all treated rat
      groups, and no significant change in the activities of CYP1A, CYP2C, CYP2D,
      CYP2E1 and CYP3A was observed for all tested AgNP doses. The results correlated
      with the observation that no AgNPs were detected in the liver sections of the
      tested rats. However, the in vitro system using rat liver microsomes demonstrated
      a strong inhibition of CYP2C (IC(50) = 28 ug/mL) and CYP2D (IC(50) = 23 ug/mL)
      activities, but not of CYP1A, CYP2E1 and CYP3A activities (IC(50) > 100 ug/mL) at
      concentrations up to 100 ug/mL of AgNPs. The inhibitory effect of AgNPs on these
      CYPs indicates the possibility of the AgNP-drug interaction when co-administered
      with some medicines and this may cause adverse effects to patients.

PMID- 22458324
TI  - Predicting the sites and energies of noncovalent intermolecular interactions
      using local properties.
AB  - Feed-forward artificial neural nets have been used to recognize H-bond donor and
      acceptor sites on drug-like molecules based on local properties (electron
      density, molecular electrostatic potential and local ionization energy, electron
      affinity, and polarizability) calculated at grid points around the molecule.
      Interaction energies for training were obtained from B97-D and omegaB97X-D/aug-cc
      pVDZ density-functional theory calculations on a series of model central
      molecules and H-bond acceptor and donor probes constrained to the grid points
      used for training. The resulting models provide maps of both classical and
      unusual H- and halogen-bonding sites. Note that these reactions result even
      though only classical H-bond donors and acceptors were used as probes around the
      central molecules. Some examples demonstrate the ability of the models to take
      the electronics of the central molecule into consideration and to provide
      semiquantitative estimates of interaction energies at low computational cost.

PMID- 22458325
TI  - Magnetite nanoparticles can be coupled to microbubbles to support multimodal
      imaging.
AB  - Microbubbles (MBs) are commonly used as injectable ultrasound contrast agent
      (UCA) in modern ultrasonography. Polymer-shelled UCAs present additional
      potentialities with respect to marketed lipid-shelled UCAs. They are more robust;
      that is, they have longer shelf and circulation life, and surface modifications
      are quite easily accomplished to obtain enhanced targeting and local drug
      delivery. The next generation of UCAs will be required to support not only
      ultrasound-based imaging methods but also other complementary diagnostic
      approaches such as magnetic resonance imaging or computer tomography. This work
      addresses the features of MBs that could function as contrast agents for both
      ultrasound and magnetic resonance imaging. The results indicate that the
      introduction of iron oxide nanoparticles (SPIONs) in the poly(vinyl alcohol)
      shell or on the external surface of the MBs does not greatly decrease the
      echogenicity of the host MBs compared with the unmodified one. The presence of
      SPIONs provides enough magnetic susceptibility to the MBs to accomplish good
      detectability both in vitro and in vivo. The distribution of SPIONs on the shell
      and their aggregation state seem to be key factors for the optimization of the
      transverse relaxation rate.

PMID- 22458326
TI  - Biomarkers of exposure to aromatic hydrocarbons and methyl tert-butyl ether in
      petrol station workers.
AB  - This cross-sectional study was aimed at reconstructing the exposure to gasoline
      in 102 petrol station attendants by environmental and biological monitoring of
      benzene, toluene, ethylbenzene and xylene (BTEX) and biomonitoring of methyl tert
      butyl ether (MTBE). Airborne BTEX were higher for manual refuelers than self
      service assistants and were highly correlated with each other. Significant
      relationships were found between airborne BTX and the corresponding urinary
      solvents (U-BTX) and beween airborne B and urinary MTBE (U-MTBE). Smokers
      eliminated higher values of U-B, trans,trans-muconic (t,t-MA) and S
      phenylmercapturic (S-PMA) acids but not U-MTBE. All these biomarkers were,
      however, significantly raised during the shift, independently from smoking.
      Linear regression confirmed that occupational exposure was a main predictor of U
      MTBE, U-B and S-PMA values, both the latter confounded by smoking habits. The
      study supports the usefulness of biomonitoring even at low exposure levels.

PMID- 22458327
TI  - Screening for autism in extremely preterm infants: problems in interpretation.
AB  - AIM: The aim of this article was to report the prevalence of, and risk factors
      for, positive autism screens using the Modified Checklist for Autism in Toddlers
      (M-CHAT) in children born extremely preterm in England. METHOD: All children born
      at not more than 26 weeks' gestational age in England during 2006 were recruited
      to the EPICure-2 study. At 2 years of age, postal questionnaires incorporating
      the M-CHAT and additional developmental questions were sent to the parents of
      each survivor (n=1031; 499 male, 532 female), of which 523 (266 male, 257 female;
      51%) were returned completed. RESULTS: The prevalence of positive M-CHAT screens
      in this extremely preterm population was 41% (216/523; 130 male; 86 female).
      Severe bronchopulmonary dysplasia, administration of postnatal steroids, late
      onset bacteraemia, and being male were statistically significantly associated
      with a positive screen. Coexisting disabilities were present in 320 (62%)
      children. Of 200 children without disability, 16.5% screened positive. In
      contrast, 63 (95.5%) of those with severe motor impairment (odds ratio 42; 95%
      confidence interval [CI] 12.9-135) and 175 (55.9%) of those with cognitive
      impairment (odds ratio 5.3; CI 3.5-8) screened positive. All children with a
      significant vision or hearing impairment screened positive. INTERPRETATION: The
      prevalence of positive M-CHAT screens in extremely preterm children is high,
      especially in children with neurodevelopmental impairment. Positive screens
      should be interpreted in the light of other neurodevelopmental sequelae in
      clinical practice to avoid false-positive referrals.

PMID- 22458328
TI  - A new design immunotoxin for killing high-grade glioma U87 cells: from in vitro
      to in vivo.
AB  - A new wave of engineered antibodies, leading to increased effectiveness of
      functions such as antibody-dependent cell-mediated cytotoxicity or complement
      dependent cytotoxicity, is being evaluated in clinical settings. Several, such as
      immunotoxins, are expected to receive approval for usage soon. In this study,
      using a cognate heavy framework region (HFR2), two complementarity-determining
      regions (CDRs, i.e., LCDR1 and HCDR3) were fused to the first 388 amino acid
      residues of diphtheria toxin (DT388) to establish the immunotoxin IT-87. It was
      found that the mimetics of LCDR1-HFR2-HCDR3 retained the antigen recognition of
      their parent antibody. The immunotoxin IT-87 could especially kill the U87 MG
      glioblastoma cell line, the targets of the parent antibody, in vitro; however,
      the IT-87 could not kill Rajicells. In SCID mice bearing both U87 and Raji cells,
      the IT-87 directly targeted the U87-induced tumors (via tumor-specific surface
      markers) and inhibited the growth of the cells in vivo over a 20-day daily IT-87
      treatment period. It is believed that the design of this particular immunotoxin
      could be the basis for even more promising molecules to be used in the treatment
      of human cancers.

PMID- 22458329
TI  - Dental postoperative bleeding complications in patients with suspected and
      documented liver disease.
AB  - OBJECTIVES: The aims of this study were to determine the frequency of bleeding
      complications following dental procedures in patients with known or suspected
      chronic liver disease and whether international normalized ratio (INR)
      determination could aid in predicting bleeding complications in these patients.
      PATIENTS AND METHOD: We identified 90 patients (mean age: 51 +/- 9 years) in this
      retrospective chart review. Sixty-nine patients had a known history of chronic
      liver disease and 21 had suspected chronic liver disease. Descriptive statistics
      were determined. Independent sample t-test and one-way variance test were
      utilized for continuous variables and chi-square test for dichotomous variables.
      RESULTS: The mean INR value for all patients was 1.2 +/- 0.3. The INR value was
      significantly associated with the diagnosis of liver cirrhosis, the diagnoses of
      Hepatitis B and C together, the presence of ascites alone, and the number of
      clinical signs and symptoms (i.e. ascites, jaundice and encephalopathy) present.
      Nine patients with INR values between 1.5 and 2 underwent invasive dental
      procedures without postoperative bleeding complications. CONCLUSION: There were
      no episodes of postoperative bleeding in patients. The findings suggest that
      clinicians should not rely solely on an INR value to predict post-procedure
      bleeding in patients with liver disease.

PMID- 22458331
TI  - Capability beliefs regarding evidence-based practice are associated with
      application of EBP and research use: validation of a new measure.
AB  - BACKGROUND: Beliefs about capabilities, or self-efficacy, is a construct
      originating in social cognitive psychology. Capability beliefs have been found to
      be positively associated with intention and healthcare practice behaviour. A
      measure of an individual's beliefs about his/her capability to apply the
      components of evidence-based practice (EBP) has potential to be useful in
      implementation research. AIMS: To evaluate the concurrent validity and internal
      structure of a new scale measuring nurses' capability beliefs regarding EBP.
      METHODS: Data were taken from a prospective longitudinal study in Sweden (the
      Longitudinal Analyses of Nursing Education and Entry in Worklife [LANE]). A
      cohort of nursing students who graduated in the autumn of 2004 that was followed
      up 2 years after their graduation was used (n= 1,256). Concurrent validity was
      tested relating different levels of capability beliefs to extent of research use
      and application of EBP. An item-response approach was applied in the evaluation
      of internal structure of the proposed scale (six items). RESULTS: The
      psychometric analyses indicated that the six items could be summed to reflect a
      one-dimensional scale. Nurses with the highest level of capability beliefs
      reported that they used research findings in clinical practice more than twice as
      often as those with lower levels of capability beliefs. They also participated in
      the implementation of evidence seven times more often. IMPLICATIONS: There is a
      need for further studies of the construct and predictive validity of the scale.
      It should also be validated in other groups of health professionals. Learning
      including mastery experiences, role modelling, social persuasion, and manageable
      stress could be used in undergraduate education as well as practice development
      to increase beliefs about capabilities which might open the way to increased
      application of EBP in healthcare practice. CONCLUSIONS: This new measure is well
      grounded in social cognitive theory, functions as a one-dimensional scale and
      possesses promising properties of concurrent validity.

PMID- 22458330
TI  - Involvement of multiple distinct Bordetella receptor proteins in the utilization
      of iron liberated from transferrin by host catecholamine stress hormones.
AB  - Bordetella bronchiseptica is a pathogen that can acquire iron using its native
      alcaligin siderophore system, but can also use the catechol xenosiderophore
      enterobactin via the BfeA outer membrane receptor. Transcription of bfeA is
      positively controlled by a regulator that requires induction by enterobactin.
      Catecholamine hormones also induce bfeA transcription and B. bronchiseptica can
      use the catecholamine noradrenaline for growth on transferrin. In this study, B.
      bronchiseptica was shown to use catecholamines to obtain iron from both
      transferrin and lactoferrin in the absence of siderophore. In the presence of
      siderophore, noradrenaline augmented transferrin utilization by B.
      bronchiseptica, as well as siderophore function in vitro. Genetic analysis
      identified BfrA, BfrD and BfrE as TonB-dependent outer membrane catecholamine
      receptors. The BfeA enterobactin receptor was found to not be involved directly
      in catecholamine utilization; however, the BfrA, BfrD and BfrE catecholamine
      receptors could serve as receptors for enterobactin and its degradation product
      2,3-dihydroxybenzoic acid. Thus, there is a functional link between enterobactin
      dependent and catecholamine-dependent transferrin utilization. This investigation
      characterizes a new B. bronchiseptica mechanism for iron uptake from transferrin
      that uses host stress hormones that not only deliver iron directly to
      catecholamine receptors, but also potentiate siderophore activity by acting as
      iron shuttles.

PMID- 22458332
TI  - Gender variance in childhood and sexual orientation in adulthood: a prospective
      study.
AB  - INTRODUCTION: Several retrospective and prospective studies have reported on the
      association between childhood gender variance and sexual orientation and gender
      discomfort in adulthood. In most of the retrospective studies, samples were drawn
      from the general population. The samples in the prospective studies consisted of
      clinically referred children. In understanding the extent to which the
      association applies for the general population, prospective studies using random
      samples are needed. AIM: This prospective study examined the association between
      childhood gender variance, and sexual orientation and gender discomfort in
      adulthood in the general population. METHODS: In 1983, we measured childhood
      gender variance, in 406 boys and 473 girls. In 2007, sexual orientation and
      gender discomfort were assessed. MAIN OUTCOME MEASURES: Childhood gender variance
      was measured with two items from the Child Behavior Checklist/4-18. Sexual
      orientation was measured for four parameters of sexual orientation (attraction,
      fantasy, behavior, and identity). Gender discomfort was assessed by four
      questions (unhappiness and/or uncertainty about one's gender, wish or desire to
      be of the other gender, and consideration of living in the role of the other
      gender). RESULTS: For both men and women, the presence of childhood gender
      variance was associated with homosexuality for all four parameters of sexual
      orientation, but not with bisexuality. The report of adulthood homosexuality was
      8 to 15 times higher for participants with a history of gender variance (10.2% to
      12.2%), compared to participants without a history of gender variance (1.2% to
      1.7%). The presence of childhood gender variance was not significantly associated
      with gender discomfort in adulthood. CONCLUSIONS: This study clearly showed a
      significant association between childhood gender variance and a homosexual sexual
      orientation in adulthood in the general population. In contrast to the findings
      in clinically referred gender-variant children, the presence of a homosexual
      sexual orientation in adulthood was substantially lower.

PMID- 22458333
TI  - Relation between physical activity and exercise capacity of >=5 metabolic
      equivalents in middle- and older-aged patients with chronic heart failure.
AB  - PURPOSE: Patients with exercise capacity of <5 metabolic equivalents (METs) are
      considered to have a high risk of death. The aim of this study was to determine
      age-related differences in physical activity associated with an exercise capacity
      of >=5 METs in chronic heart failure (CHF) outpatients. METHODS: We enrolled 157
      stable CHF patients (79.6% men, age 60.3 +/- 11.5 years). Patients were divided
      into two age-based groups (middle-aged, <65 years, n = 97) and (older-aged, >=65
      years, n = 60). Peak oxygen uptake (peak (V)O(2)) was assessed by cardiopulmonary
      exercise testing. We further divided patients into groups according to exercise
      capacity: >=5 METs and <5 METs. Physical activity was assessed by measuring the
      average number of steps/day for 1 week with an electronic pedometer. RESULTS:
      Receiver-operating characteristic curves were used to select cutoff values for
      steps associated with an exercise capacity of >=5 METs in the middle- and older
      aged patients. Cutoff values of 6045 steps in the middle-aged and 6070 steps in
      the older-aged patients were determined. CONCLUSIONS: Both middle- and older-aged
      CHF patients with exercise capacity of >=5 METs completed approximately 6000
      steps/day. This could become a target amount for minimal physical activity that
      could contribute to increased exercise capacity in CHF patients. IMPLICATIONS FOR
      REHABILITATION: * Middle-aged and older-aged chronic heart failure (CHF) patients
      with a measured exercise capacity of >=5 METs completed approximately 6000
      steps/day as measured by electronic pedometer. * This amount of steps could
      become a target amount for minimal physical activity that could contribute to
      increased exercise capacity in CHF patients.

PMID- 22458334
TI  - Models of intellectual disability: towards a perspective of (poss)ability.
AB  - BACKGROUND: The social and medical models of disability configure the
      relationship between disability and impairment differently. Neither of these
      models has provided a comprehensive theoretical or practical basis for talking
      about intellectual disability (ID). Models that emphasise the interactive nature
      of disability appear to be more promising. This study explores the ways in which
      models of disability are reflected in disability discourse in an empirical
      discourse analysis conducted in the Eastern Cape Province of South Africa.
      METHODS: Q methodology was used in this study as a discourse analysis tool.
      Adults with ID, parents of children with ID and professionals who work with
      people with ID completed a sorting task where they stated the degree to which
      they agreed or disagreed with statements that are made about people with ID. This
      exercise resulted in a pattern of responses for each participant, termed a Q sort
      and these were used as data in a factor analysis using dedicated Q method
      software. A second order factor analysis was then performed on the resulting
      factors. RESULTS: Four discourses were identified: the Social Model/Human Rights
      Discourse, the Medical Model/Professional Religious Discourse, the Community
      Model/Community Religious Discourse and the Interactive Discourse. Except for the
      last one, each of these discourses adopts a model of disability with a static
      view of impairment as fixed. The Interactive Discourse appears to be related to
      dynamic, environmental conceptions of disability where competence is built
      through social interaction. CONCLUSIONS: A theory of (poss)ability is proposed
      and some of its concerns are suggested. This perspective views impairment as an
      interaction between individuals and their environment and postulates that
      competence is a function of context, rather than a property of the individual.

PMID- 22458335
TI  - Cognitive barriers to readiness to change in alcohol-dependent patients.
AB  - BACKGROUND: Patients' personal investment and readiness to change have proved to
      be a prerequisite for the successful treatment of alcohol addiction. The aim of
      this study was to determine the contribution of cognitive functions to the
      motivation process to abandon maladjusted behavior in favor of a healthier
      lifestyle. METHODS: An adapted version of the "readiness to change" questionnaire
      was completed by 31 alcohol-dependent patients after detoxification and at
      alcohol treatment entry. This tool is designed to assess the 3 main stages of
      motivation to change regarding alcohol consumption: precontemplation (substance
      abuse and no intention to stop drinking), contemplation (strong intention to
      change habits but ambivalent behavior), and action (cessation of excessive
      alcohol consumption and behavioral changes for healthier habits) stages. Patients
      and 37 healthy controls also underwent an extensive neuropsychological battery
      including episodic memory, metamemory, executive functions, and decision-making
      assessment. RESULTS: When alcohol-dependent patients were considered as a group,
      the mean score on the action subscale was significantly higher than the
      precontemplation and contemplation ones. Nevertheless, when the stage of change
      reached by each patient was considered individually, we found that some alcohol
      dependent patients were still in the earlier precontemplation and contemplation
      stages. Stepwise regression analysis revealed links between impaired memory and
      executive functions and low motivation, and between good decision-making skills
      and high motivation. CONCLUSIONS: Our results suggest that a set of complementary
      cognitive abilities is needed to achieve awareness and resolve ambivalence toward
      alcohol addiction, which is essential for activating the desire to change
      problematic behavior.

PMID- 22458336
TI  - Effect of a disease-specific advance care planning intervention on end-of-life
      care.
AB  - OBJECTIVES: To compare patient preferences for end-of-life care with care
      received at the end of life. DESIGN: A randomized controlled trial was conducted
      with individuals with congestive heart failure or end-stage renal disease and
      their surrogates who were randomized to receive patient-centered advance care
      planning (PC-ACP) or usual care. SETTING: Two centers in Wisconsin with
      associated clinics and dialysis units. PARTICIPANTS: Of the 313 individuals and
      their surrogates who completed entry data, 110 died. INTERVENTION: During PC-ACP,
      the trained facilitator assessed individual and surrogate understanding of and
      experiences with the illness, provided information about disease-specific
      treatment options and their benefits and burden, assisted in documentation of
      treatment preferences, and assisted the surrogates in understanding the patient's
      preferences and the surrogate's role. MEASUREMENTS: Preferences were documented
      and compared with care received at the end of life according to surrogate
      interviews or medical charts. RESULTS: Patients (74%) frequently continued to
      make their own decisions about care to the end. The experimental group had fewer
      (1/62) cases in which patients' wishes about cardiopulmonary resuscitation were
      not met than in the control group (6/48) but not significantly so. Significantly
      more experimental patients withdrew from dialysis than controls. CONCLUSION:
      Patients and their surrogates were generally willing to discuss preferences with
      a trained facilitator. Most patients received the care they desired at end of
      life or altered their preferences to be in accord with the care they could
      receive. A larger sample with surrogate decision-makers is needed to detect
      significant differences.

PMID- 22458337
TI  - Synthesis of ureidomuraymycidine derivatives for structure-activity relationship
      studies of muraymycins.
AB  - One of the key constituents of the muraymycins is the 6-membered cyclic
      guanidine,  (2S,3S)-muraymycidine (or epi-capreomycidine). In order to diversify
      the structure of the oligopeptide moiety of the muraymycins for thorough
      structure-activity relationship studies, we have developed a highly
      stereoselective synthesis of ureidomuraymycidine derivatives with the lactone 4a.

PMID- 22458339
TI  - Copper-mediated aerobic fluoroalkylation of arylboronic acids with fluoroalkyl
      iodides at room temperature.
AB  - A Cu-mediated ligandless aerobic fluoroalkylation of arylboronic acids under mild
      conditions is described for the first time. The reaction tolerates a wide range
      of functional groups, allowing for further transformation. Mechanistic studies
      suggest that [R(f)Cu] is the active Cu species that forms the desired
      perfluoroalkylarenes and that [R(f)Cu] is generated from [PhCu] by either an
      oxidative addition/reductive elimination mechanism or nucleophilic substitution
      via a halogen "ate" intermediate.

PMID- 22458340
TI  - Measuring sidewalk distances using Google Earth.
AB  - BACKGROUND: Physical activity is an important determinant of health. Walking is
      the most common physical activity performed by adults and the presence of
      sidewalks along roads is a determinant of walking. Geographic information systems
      (GIS) can be used to measure sidewalks; however, GIS sidewalk data are difficult
      to access. The purpose of this study was to present a new GIS method for
      measuring the distance and coverage of sidewalks along roadways. METHODS: The new
      method contains three stages. Stage 1 involves calculating the distance of all
      road segments within the region of interest (e.g., neighborhood), extracting
      geospatial information on these road segments, and saving this information as a
      Google Earth file. This stage was performed in ArcGIS software. Stage 2 involves
      opening the extracted road segment geospatial data in Google Earth, visually
      examining road segments to see if they contain sidewalks, and deleting road
      segments without sidewalks. Stage 3 involves importing the modified road
      geospatial data into ArcGIS and calculating the length of road segments with
      sidewalks. The new method was tested in 315 sites across Canada. Each site
      consisted of a one km radius circular buffer surrounding a school. RESULTS: A
      detailed, step-by-step protocol is provided in the paper. The length of road
      segments with sidewalks in the testing sites ranged from 0.00 to 55.05 km (median
      16.20 km). When expressed relative to the length of all road segments, the length
      of road segments with sidewalks ranged from 0% to 100% (median 53%). By
      comparison to urban testing sites, rural sites had shorter sidewalk lengths and a
      smaller proportion of the roads had sidewalk coverage. CONCLUSION: This study
      provides a new GIS protocol that researchers can use to measure the distance and
      coverage of sidewalks along roadways.

PMID- 22458338
TI  - Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T
      lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a
      causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to
      HTLV-1, causes no known overt disease. HTLV gene products are engaged in a
      dynamic struggle of activating and antagonistic interactions with host cells.
      Investigations focused on one or a few genes have identified several human
      factors interacting with HTLV viral proteins. Most of the available interaction
      data concern the highly investigated HTLV-1 Tax protein. Identifying shared and
      distinct host-pathogen protein interaction profiles for these two viruses would
      enlighten how they exploit distinctive or common strategies to subvert cellular
      pathways toward disease progression. RESULTS: We employ a scalable methodology
      for the systematic mapping and comparison of pathogen-host protein interactions
      that includes stringent yeast two-hybrid screening and systematic retest, as well
      as two independent validations through an additional protein interaction
      detection method and a functional transactivation assay. The final data set
      contained 166 interactions between 10 viral proteins and 122 human proteins.
      Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 
      encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate
      a diverse set of cellular processes including the ubiquitin-proteasome system,
      the apoptosis, different cancer pathways and the Notch signaling pathway.
      CONCLUSIONS: This study constitutes a first pass, with homogeneous data, at
      comparative analysis of host targets for HTLV-1 and -2 retroviruses, complements
      currently existing data for formulation of systems biology models of retroviral
      induced diseases and presents new insights on biological pathways involved in
      retroviral infection.

PMID- 22458341
TI  - Reducing serious fall-related injuries in acute hospitals: are low-low beds a
      critical success factor?
AB  - AIM: This article is a report of a study of associations between occurrence of
      serious fall-related injuries and implementation of low-low beds at The Northern
      Hospital, Victoria, Australia. BACKGROUND: A 9-year evaluation at The Northern
      Hospital found an important reduction in fall-related injuries after the 6-PACK
      falls prevention program was implemented. Low-low beds are a key component of the
      6-PACK that aims to decrease fall-related injuries. DESIGN: A retrospective
      cohort study. METHODS: Retrospective audit of The Northern Hospital inpatients
      admitted between 1999-2009. Changes in serious fall-related injuries throughout
      the period and associations with available low-low beds were analysed using
      Poisson regression. RESULTS: During the observation of 356,158 inpatients, there
      were 3946 falls and 1005 fall-related injuries of which 60 (5.9%) were serious
      (55 fractures and five subdural haematomas). Serious fall-related injuries
      declined significantly throughout the period. When there was one low-low bed to
      nine or more standard beds there was no statistically significant decrease in
      serious fall-related injuries. An important reduction only occurred when there
      was one low-low bed to three standard beds. CONCLUSION: The 6-PACK program has
      been in place since 2002 at The Northern Hospital. Throughout this time serious
      fall-related injuries have decreased. There appears to be an association between
      serious fall-related injuries and the number of available low-low beds. Threshold
      numbers of these beds may be required to achieve optimal usability and
      effectiveness. A randomized controlled trial is required to give additional
      evidence for use of low-low beds for injury prevention in hospitals.

PMID- 22458342
TI  - New iron(II) spin crossover coordination polymers [Fe(MU-atrz)3]X2.2H2O (X = ClO4
      , BF4-) and [Fe(MU-atrz)(MU-pyz)(NCS)2].4H2O with an interesting solvent effect.
AB  - A potential bridging triazole-based ligand, atrz (trans-4,4'-azo-1,2,4-triazole),
      is chosen to serve as building sticks and incorporated with a spin crossover
      metal center to form a metal organic framework. Coordination polymers of iron(II)
      with the formula [Fe(MU-atrz)(3)]X(2).2H(2)O (where X = ClO(4)(-) (1.2H(2)O) and
      BF(4)(-) (2.2H(2)O)) in a 3D framework and [Fe(MU-atrz)(MU-pyz)(NCS)(2)].4H(2)O
      (3.4H(2)O) in a 2D layer structure were synthesized and structurally
      characterized. The magnetic measurements of 1.2H(2)O and 2.2H(2)O reveal spin
      transitions near room temperature; that of 3 exhibits an abrupt spin transition
      at ~200 K with a wide thermal hysteresis, and the spin transition behavior of
      these polymers are apparently correlated with the water content of the sample.
      Crystal structures have been determined both at high spin and at low spin states
      for 1.2H(2)O, 2.2H(2)O, and 3.4H(2)O. Each iron(II) center in 1.2H(2)O and
      2.2H(2)O is octahedrally coordinated with six MU-atrz ligands, which in turn
      links the other Fe center forming a strong three-dimensional (3D) network;
      counteranion and water molecules are located in the voids of the lattice. The
      FeN(6) octahedron of 3.4H(2)O is formed with two atrz, two pyrazine (pyz)
      ligands, and two NCS(-) ligands, where the ligands atrz and pyz are bridged
      between iron centers forming a 2D layer polymer. A zigzag chain of water
      molecules is found between the layers, and there is a distinct correlation
      between the thermal hysteresis with the amount of water molecules the exist in
      the crystal.

PMID- 22458344
TI  - A cervical ligamentum flavum cyst in an 82-year-old woman presenting with spinal
      cord compression: a case report and review of the literature.
AB  - INTRODUCTION: We report on a very rare case of a cervical ligamentum flavum cyst,
      which presented with progressive myelopathy and radiculopathy. The cyst was
      radically extirpated and our patient showed significant recovery. A review of the
      relevant literature yielded seven cases. CASE PRESENTATION: An 82-year-old Greek
      woman presented with progressive bilateral weakness of her upper extremities and
      causalgia, cervical pain, episodes of upper extremity numbness and significant
      walking difficulties. Her neurological examination showed diffusely decreased
      motor strength in both her upper and lower extremities. Magnetic resonance
      imaging of her cervical spine demonstrated a large, well-demarcated cystic lesion
      on the dorsal aspect of her spinal cord at the C3 to C4 level, significantly
      compressing the spinal cord at this level, in close proximity to the yellow
      ligament and the C3 left lamina. The largest diameter of this lesion was 1.4 cm,
      and there was no lesion enhancement after the intravenous administration of a
      paramagnetic contrast. The lesion was surgically removed after a bilateral C3
      laminectomy. The thick cystic wall was yellow and fibro-elastic in consistency,
      while its content was gelatinous and yellow-brownish. A postoperative cervical
      spine magnetic resonance image was obtained before her discharge, demonstrating
      decompression of her spinal cord and dural expansion. Her six-month follow-up
      evaluation revealed complete resolution of her walking difficulties, improvement
      in the muscle strength of her arms (4+/5 in all the affected muscle groups), no
      causalgia and a significant decrease in her preoperative upper extremity
      numbness. CONCLUSION: Cervical ligamentum flavum cysts are rare benign lesions,
      which should be included in the list of differential diagnosis of spinal cystic
      lesions. They can be differentiated from other intracanalicular lesions by their
      hypointense appearance on T1-weighted and hyperintense appearance on T2-weighted
      magnetic resonance images, with contrast enhancement of the cystic wall. Surgical
      extirpation of the cyst is required for symptom alleviation and decompression of
      the spinal cord. The outcome of these cysts is excellent with no risk of
      recurrence.

PMID- 22458343
TI  - Study protocol- Lumbar Epidural steroid injections for Spinal Stenosis (LESS): a
      double-blind randomized controlled trial of epidural steroid injections for
      lumbar spinal stenosis among older adults.
AB  - BACKGROUND: Lumbar spinal stenosis is one of the most common causes of low back
      pain among older adults and can cause significant disability. Despite its
      prevalence, treatment of spinal stenosis symptoms remains controversial. Epidural
      steroid injections are used with increasing frequency as a less invasive,
      potentially safer, and more cost-effective treatment than surgery. However, there
      is a lack of data to judge the effectiveness and safety of epidural steroid
      injections for spinal stenosis. We describe our prospective, double-blind,
      randomized controlled trial that tests the hypothesis that epidural injections
      with steroids plus local anesthetic are more effective than epidural injections
      of local anesthetic alone in improving pain and function among older adults with
      lumbar spinal stenosis. METHODS: We will recruit up to 400 patients with lumbar
      central canal spinal stenosis from at least 9 clinical sites over 2 years.
      Patients with spinal instability who require surgical fusion, a history of prior
      lumbar surgery, or prior epidural steroid injection within the past 6 months are
      excluded. Participants are randomly assigned to receive either ESI with local
      anesthetic or the control intervention (epidural injections with local anesthetic
      alone). Subjects receive up to 2 injections prior to the primary endpoint at 6
      weeks, at which time they may choose to crossover to the other
      intervention.Participants complete validated, standardized measures of pain,
      functional disability, and health-related quality of life at baseline and at 3
      weeks, 6 weeks, and 3, 6, and 12 months after randomization. The primary outcomes
      are Roland-Morris Disability Questionnaire and a numerical rating scale measure
      of pain intensity at 6 weeks. In order to better understand their safety, we also
      measure cortisol, HbA1c, fasting blood glucose, weight, and blood pressure at
      baseline, and at 3 and 6 weeks post-injection. We also obtain data on resource
      utilization and costs to assess cost-effectiveness of epidural steroid injection.
      DISCUSSION: This study is the first multi-center, double-blind RCT to evaluate
      the effectiveness of epidural steroid injections in improving pain and function
      among older adults with lumbar spinal stenosis. The study will also yield data on
      the safety and cost-effectiveness of this procedure for older adults. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01238536.

PMID- 22458345
TI  - Effect of sample storage on blood crossmatching in horses.
AB  - BACKGROUND: Blood samples banked for up to 1 month are typically used to perform
      pretransfusion testing in humans and small animals, but this has not been
      validated using blood from horses. HYPOTHESIS: Compatibility of equine blood
      samples is repeatable using fresh samples, and reproducible using donor blood
      samples stored for up to 4 weeks. ANIMALS: Six healthy adult horses. METHODS:
      Randomized, blinded experimental study. Immunologic compatibility of the blood of
      all horses was assessed using a major and minor saline agglutination and
      hemolysin crossmatch using blood samples refrigerated for 0-4 weeks and fresh
      blood from the same horses. Crossmatch results were scored and then compared to
      identify changes of compatibility in each of the 4 tests. In addition,
      repeatability of the crossmatch technique itself was assessed by performing 6
      iterations of this procedure in immediate succession with fresh blood from 3
      horses. RESULTS: No significant difference in crossmatch results was found using
      fresh blood (P = .39-1.00). Reproducibility was poor using blood stored for 1-4
      weeks, especially in tests using stored erythrocytes (major antigen
      crossmatches), with significant differences from baseline at all weeks (P < .05);
      13 of these differences were positive, indicating poorer compatibility.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Equine blood crossmatching is repeatable
      using fresh blood, although decreased apparent compatibility after storage makes
      exclusion of compatible donors more likely than mistaken administration of
      incompatible blood. These data suggest that fresh samples should be collected
      from potential donors before crossmatching equine blood.

PMID- 22458346
TI  - Naturally occurring flavonoids as inhibitors of purified cytosolic glutathione S
      transferase.
AB  - Flavonoids are known to modulate catalytic activity and expression of various
      enzymes. Glutathione S-transferases (GSTs) are the important biotransformation
      enzymes defending cells against potentially toxic xenobiotics. Therefore, the
      modulation of GST activity may influence detoxification of xenobiotics. The aim
      of this study was to evaluate the in vitro inhibitory activity of several dietary
      flavonoids towards purified equine liver cytosolic GST. Pure GST was incubated in
      the presence or absence of flavonoids (10 nM-100 uM), its activity was assayed
      using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate, and half maximal
      inhibitory concentrations (IC(50)) were determined. The obtained results were
      confirmed by GST activity staining of native polyacrylamide gel electrophoresis
      (PAGE) gels. For the most potent inhibitor, the inhibition kinetics study was
      performed. From 24 flavonoids tested, the most potent GST inhibitor was
      gallocatechin gallate (IC(50) = 1.26 uM). The inhibition kinetics of this
      compound followed noncompetitive mechanism versus both glutathione (K(i) = 35.9
      uM) and CDNB (K(i) = 34.1 uM). The inhibitory potency of different flavonoids for
      GST activity depended mainly on the pattern of hydroxylation and number of
      hydroxyl groups in the ring B. Especially, pyrogallol-type catechins with 3-OH
      group esterified with gallic acid showed strong potential to inhibit GST in
      vitro.

PMID- 22458347
TI  - Absorption, distribution, metabolism, and excretion of macitentan, a dual
      endothelin receptor antagonist, in humans.
AB  - Macitentan is a tissue-targeting, dual endothelin receptor antagonist, currently
      under phase 3 investigation in pulmonary arterial hypertension. In this study the
      disposition and metabolism of macitentan were investigated following
      administration of a single oral 10 mg dose of (14)C-macitentan to six healthy
      male subjects. The total radioactivity in matrices was determined using liquid
      scintillation counting. The proposed structure of metabolites was based on mass
      spectrometry characteristics and, when available, confirmed by comparison with
      reference compounds. Mean (+/- SD) cumulative recovery of radioactivity from
      faeces and urine was 73.6% (+/- 6.2%) of the administered radioactive dose, with
      49.7% (+/- 3.9%) cumulative recovery from urine, and 23.9% (+/- 4.8%) from
      faeces. In plasma, in addition to parent macitentan, ACT-132577, a
      pharmacologically active metabolite elicited by oxidative depropylation and the
      carboxylic acid metabolite ACT-373898 were identified. In urine, four entities
      were identified, with the hydrolysis product of ACT-373898 as the most abundant
      one. In faeces, five entities were identified, with the hydrolysis product of
      macitentan and ACT-132577 as the most abundant one. Concentrations of total
      radioactivity in whole blood were lower compared to plasma, which indicates that
      macitentan and its metabolites poorly bind to or penetrate into erythrocytes.

PMID- 22458348
TI  - Characteristics of children with cerebral palsy in the ORACLE children study.
AB  - AIMS: We have identified an excess of children with cerebral palsy (CP) born to
      women who received antibiotic treatment for spontaneous preterm labour (SPL).
      This nested study investigated the profile of impairment among children with CP
      in the ORACLE Children Study (OCS), and contrasted outcomes with those in 4Child,
      a population CP registry. METHOD: The study group comprised 167 children aged
      from 7 to 10 years (100 males, 67 females) with CP from the OCS, who were
      subdivided into a preterm rupture of membranes (PROM) group (87 children) and an
      SPL group (80 children). The OCS sought follow-up information regarding the
      health and behaviour of surviving children at 7 years of age in the UK using a
      parent-report postal questionnaire. Families provided further information to
      define wider aspects of function and were offered a physiotherapy assessment.
      RESULTS: The prevalence of CP was higher among children in the OCS than among
      those in 4Child (standardized morbidity ratios: SPL group, 3.12 [95% confidence
      interval {CI} 2.47-3.87); PROM group: 1.56 (CI 1.24-1.92)]. The proportion of
      children with CP born after 32 weeks of gestation was higher in in the SPL group
      (73%) than in the PROM group (30%); the prevalence of CP was higher in the SPL
      group than in the PROM group or 4Child. Children with CP in the OCS tended to
      have similar distributions of neuroimpairment as children in 4Child, but motor
      impairment and associated vision and hearing problems were found to be less
      severe. INTERPRETATION: The pattern of CP in both the PROM and the SPL groups was
      similar, but functional outcomes were milder, compared with children with CP in
      the general population. However, in these groups the risk of CP was increased
      independently of gestational age. This is consistent with findings that ongoing
      inflammatory damage can cause CP.

PMID- 22458349
TI  - The association of a distinct plasma proteomic profile with the cervical high
      grade squamous intraepithelial lesion of Uyghur women: a 2D liquid-phase
      chromatography/mass spectrometry study.
AB  - OBJECTIVE: To identify plasma protein biomarkers of cervical high-grade squamous
      intraepithelial lesion (HSIL) of Uyghur women by proteomics approach. METHODS:
      Plasma protein samples of Uyghur women with HSIL and chronic cervicitis were
      analyzed with 2D HPLC followed by detection of target proteins with Linear Trap
      Quadrupole Mass Spectrometer (LTQ MS/MS). RESULTS: We detected three upregulated
      and one downregulated protein peaks representing protein constituents
      distinguishing HSIL from controls by 2D HPLC, identified 31 target proteins by
      LTQ MS/MS. Further confirmed analysis with online software IPA(r) 8.7 and ELISA
      assay showed APOA1 and mTOR as potential biomarkers. CONCLUSIONS: A distinct
      plasma proteomic profile may be associated with HSIL of Uyghur women.

PMID- 22458350
TI  - Cognitive functioning in persons with lower limb amputations: a review.
AB  - PURPOSE: To review the literature on cognitive functioning in persons with lower
      limb amputations. METHOD: A search of the MEDLINE, PsycINFO and Web of Science
      databases was carried out. RESULTS: Thirty papers were found that met the
      inclusion criteria. The studies were characterised by heterogeneity of design,
      methodological quality, sample characteristics, assessment of cognitive
      functioning, and outcomes examined. The research published to date suggests that
      cognitive impairment is more prevalent among persons with lower limb amputations
      than in the general population, and is linked with a number of important outcomes
      in this patient group, including mobility, prosthesis use, and maintenance of
      independence following amputation. CONCLUSIONS: These findings highlight the
      importance of assessing the cognitive abilities of persons with lower limb
      amputations. An understanding of the cognitive profile of these patients could
      assist rehabilitation teams in determining their suitability for prosthetic or
      wheelchair rehabilitation, ascertaining appropriate and realistic goals for
      rehabilitation, and tailoring rehabilitation programmes to patients' strengths so
      that maximal mobility and independence is achieved. IMPLICATIONS FOR
      REHABILITATION: * Cognitive impairment appears to be more prevalent among persons
      with lower limb amputations than in the general population. * Cognitive
      impairment is negatively associated with mobility, prosthesis use, and
      maintenance of independence following amputation. * Cognitive screening prior to
      rehabilitation could assist in determining patients' suitability for prosthetic
      or wheelchair use, ascertaining appropriate goals, and tailoring rehabilitation
      to patients' strengths so as to optimise their mobility and independence.

PMID- 22458353
TI  - Formation of phosphatidylethanol and its subsequent elimination during an
      extensive drinking experiment over 5 days.
AB  - BACKGROUND: For almost 30 years, phosphatidylethanol (PEth) has been known as a
      direct marker of alcohol consumption. This marker stands for consumption in high
      amounts and for a longer time period, but it has been also detected after 1 high
      single intake of ethanol (EtOH). The aim of this study was to obtain further
      information about the formation and elimination of PEth 16:0/18:1 by simulating
      extensive drinking. METHODS: After 3 weeks of alcohol abstinence, 11 test persons
      drank an amount of EtOH leading to an estimated blood ethanol concentration of 1
      g/kg on each of 5 successive days. After the drinking episode, they stayed
      abstinent for 16 days with regular blood sampling. PEth 16:0/18:1 analysis was
      performed using liquid chromatography-tandem mass spectrometry (high-performance
      liquid chromatography 1100 system and QTrap 2000 triple quadrupole linear ion
      trap mass spectrometer. Values of blood alcohol were obtained using a
      standardized method with headspace gas chromatography flame ionization detector.
      RESULTS: Maximum measured concentrations of EtOH were 0.99 to 1.83 g/kg (mean
      1.32 g/kg). These values were reached 1 to 3 hours after the start of drinking
      (mean 1.9 hours). For comparison, 10 of 11 volunteers had detectable PEth
      16:0/18:1 values 1 hour after the start of drinking, ranging from 45 to 138 ng/ml
      PEth 16:0/18:1. Over the following days, concentrations of PEth 16:0/18:1
      increased continuously and reached the maximum concentrations of 74 to 237 ng/ml
      between days 3 and 6. CONCLUSIONS: This drinking experiment led to measurable
      PEth concentrations. However, PEth 16:0/18:1 concentrations stayed rather low
      compared with those of alcohol abusers from previous studies.

PMID- 22458354
TI  - Intrusive fathering, children's self-regulation and social skills: a mediation
      analysis.
AB  - BACKGROUND: Fathers have unique influences on children's development, and
      particularly in the development of social skills. Although father-child
      relationship influences on children's social competence have received increased
      attention in general, research on fathering in families of children with
      developmental delays (DD) is scant. This study examined the pathway of influence
      among paternal intrusive behaviour, child social skills and child self-regulatory
      ability, testing a model whereby child regulatory behaviour mediates relations
      between fathering and child social skills. METHODS: Participants were 97 families
      of children with early identified DD enrolled in an extensive longitudinal study.
      Father and mother child-directed intrusiveness was coded live in naturalistic
      home observations at child age 4.5, child behaviour dysregulation was coded from
      a video-taped laboratory problem-solving task at child age 5, and child social
      skills were measured using independent teacher reports at child age 6. Analyses
      tested for mediation of the relationship between fathers' intrusiveness and child
      social skills by child behaviour dysregulation. RESULTS: Fathers' intrusiveness,
      controlling for mothers' intrusiveness and child behaviour problems, was related
      to later child decreased social skills and this relationship was mediated by
      child behaviour dysregulation. CONCLUSIONS: Intrusive fathering appears to carry
      unique risk for the development of social skills in children with DD. Findings
      are discussed as they related to theories of fatherhood and parenting in children
      with DD, as well as implications for intervention and future research.

PMID- 22458355
TI  - Successful mobilization using a combination of plerixafor and G-CSF in pediatric
      patients who failed previous chemomobilization with G-CSF alone and possible
      complications of the treatment.
AB  - Peripheral blood stem cell (PBSC) mobilization, which uses plerixafor (AMD 3100),
      a newly developed specific inhibitor of the CXCR4 receptor, in combination with
      granulocyte-colony stimulating factor(G-CSF), has been shown to enhance the stem
      cell mobilization in adult patients, but pediatric data are scarce. We documented
      our experience with this drug in 6 Korean pediatric patients who had failed in
      chemomobilization, using G-CSF, alone. All patients were mobilized CD34+ cells
      (median, 11.08 * 106/kg: range, 6.34-28.97 * 106/kg) successfully within 2 to 3
      cycles of apheresis, without complications. A total of 7 autologous
      transplantations were performed, including 1 tandem transplantation. However, 2
      patients with brain tumors showed severe pulmonary complications, including
      spontaneous pneumomediastinum. This is the first study of PBSC mobilization with
      plerixafor in Asian pediatric patients. Furthermore our study suggests that
      mobilization with plerixafor may be effective in Korean pediatric patients, who
      have previously been heavily treated and have failed PBSC mobilization with
      classical chemomobilization, using G-CSF. However, further studies are needed to
      examine the possible complications of autologous transplantation, using a
      mobilized plerixafor product in children.

PMID- 22458356
TI  - Immobilization of biotinylated hGBP1 in a defined orientation on surfaces is
      crucial for uniform interaction with analyte proteins and catalytic activity.
AB  - Guanylate binding proteins (GBPs) belong to the dynamin superfamily of large GTP
      binding proteins. A biochemical feature common to these proteins is guanosine
      triphosphate (GTP) binding leading to self-assembly of the proteins, and this in
      turn results in higher catalytic GTP hydrolysis activity. In the case of human
      guanylate binding protein 1 (hGBP1) homodimer formation is observed after binding
      of nonhydrolyzable GTP analogs like GppNHp. hGBP1 is one of seven GBP isoforms
      identified in human. While cellular studies suggest heterocomplex formation of
      various isoforms biochemical binding studies in quantitative terms are lacking.
      In this work we established a method to study hGBP1 interactions by attaching
      this protein in a defined orientation to a surface allowing for interaction with
      molecules from the solution. Briefly, specifically biotinylated hGBP1 is attached
      to a streptavidin layer on a self-assembled monolayer (SAM) surface allowing for
      characterization of the packing density of the immobilized protein by surface
      plasmon resonance (SPR) technology and atomic force microscopy (AFM),
      respectively. In addition, the enzymatic activity of immobilized hGBP1 and the
      kinetics of interaction with binding partners in solution are quantified. We
      present a procedure for attaching an enzyme in a defined orientation to a surface
      which exposes its active end, the GTPase domain to the solution resulting in a
      homogeneous population of this enzyme in terms of enzymatic activity and of
      interaction with soluble proteins.

PMID- 22458357
TI  - Orofacial diseases in solid organ and hematopoietic stem cell transplant
      recipients.
AB  - OBJECTIVE: Solid organ transplant (SOT) and hematopoietic stem cell transplant
      (HSCT) recipients are at risk of several diseases, principally attributable to
      immunosuppression. This global overview of SOT/HSCT-associated orofacial diseases
      is aimed at providing a practical instrument for the oral healthcare management
      of SOT/HSCT recipients. METHODS: Literature search was made through MEDLINE. The
      associations between orofacial diseases and SOT/HSCT were assessed using
      observational studies and case series and were classified into 'association', 'no
      association', and 'unclear association'. RESULTS: Lip/oral cancers, drug-induced
      gingival overgrowth (DIGO), infections, including hairy leukoplakia and, less
      frequently, post-transplantation lymphoproliferative disorders (PTLDs) and oral
      lichenoid lesions of graft-versus-host disease (GVHD), were associated with SOT.
      Lip/oral cancers, GVHD, mucositis, DIGO, infections and, less frequently, PTLDs
      were associated with HSCT. Associations of orofacial granulomatosis-like lesions
      and oral mucosa-associated lymphoid tissue-type lymphoma with SOT, and of
      pyogenic granuloma and hairy leukoplakia with HSCT were unclear. Periodontal
      disease and dental caries were not associated with SOT/HSCT. For none of the
      local treatments was there a strong evidence of effectiveness. CONCLUSIONS: Solid
      organ transplant/HSCT recipients are at risk of orofacial diseases. Adequate
      management of these patients alleviates local symptoms responsible for impaired
      eating, helps prevent systemic and lethal complications, and helps where dental
      healthcare has been neglected.

PMID- 22458359
TI  - Surgical treatment of congenital biliary duct cyst.
AB  - BACKGROUND: It is acknowledged that total cyst excision is a safe and ideal
      surgical treatment for congenital biliary duct cyst, compared to simple internal
      drainage. The aim of this study was to determine the optimal operation occasion
      and the effect of laparoscopy on congenital biliary duct cyst based upon total
      cyst excision. METHODS: From January 2002 to January 2011, 217 patients were
      admitted to Southwest Hospital for congenital biliary duct cyst. To determine the
      optimal surgery occasion, we divided these subjects into three groups, the infant
      group (age <= 3 years), the immaturity group (3 < age <= 18 years), and the
      maturity group (age > 18 years), and then evaluated the feasibility, risk and
      long-term outcome after surgery in the three groups. To analyze the effect of
      laparoscopic technique on congenital biliary duct cyst, we divided the patients
      into the laparoscopy and the open surgery groups. RESULTS: Among the three
      groups, the morbidity from cholangiolithiasis before surgical treatment had
      obvious discrepancy (p < 0.05) (lowest in the infant group), and intraoperative
      blood loss also had apparent diversity (p < 0.05). Furthermore, long-term
      outcomes (secondary cholangiolithiasis, stoma stenosis and cholangiocarcinoma)
      showed no significant difference between different groups (p > 0.05).Similarly,
      no significant discrepancy was observed in the morbidity from postoperative
      complications or long-term postoperative complications (p > 0.05) between the
      laparoscopic and the open surgery groups. CONCLUSIONS: We conclude that total
      cyst excision should be performed as early as possible. The optimal treatment
      occasion is the infant period, and laparoscopic resection may be a new safe and
      feasible minimally invasive surgery for this disease.

PMID- 22458358
TI  - Tailored enrichment strategy detects low abundant small noncoding RNAs in HIV-1
      infected cells.
AB  - BACKGROUND: The various classes of small noncoding RNAs (sncRNAs) are important
      regulators of gene expression across divergent types of organisms. While a
      rapidly increasing number of sncRNAs has been identified over recent years, the
      isolation of sncRNAs of low abundance remains challenging. Virally encoded
      sncRNAs, particularly those of RNA viruses, can be expressed at very low levels.
      This is best illustrated by HIV-1 where virus encoded sncRNAs represent
      approximately 0.1-1.0% of all sncRNAs in HIV-1 infected cells or were found to be
      undetected. Thus, we applied a novel, sequence targeted enrichment strategy to
      capture HIV-1 derived sncRNAs in HIV-1 infected primary CD4+ T-lymphocytes and
      macrophages that allows a greater than 100-fold enrichment of low abundant
      sncRNAs. RESULTS: Eight hundred and ninety-two individual HIV-1 sncRNAs were
      cloned and sequenced from nine different sncRNA libraries derived from five
      independent experiments. These clones represent up to 90% of all sncRNA clones in
      the generated libraries. Two hundred and sixteen HIV-1 sncRNAs were
      distinguishable as unique clones. They are spread throughout the HIV-1 genome,
      however, forming certain clusters, and almost 10% show an antisense orientation.
      The length of HIV-1 sncRNAs varies between 16 and 89 nucleotides with an
      unexpected peak at 31 to 50 nucleotides, thus, longer than cellular microRNAs or
      short-interfering RNAs (siRNAs). Exemplary HIV-1 sncRNAs were also generated in
      cells infected with different primary HIV-1 isolates and can inhibit HIV-1
      replication. CONCLUSIONS: HIV-1 infected cells generate virally encoded sncRNAs,
      which might play a role in the HIV-1 life cycle. Furthermore, the enormous
      capacity to enrich low abundance sncRNAs in a sequence specific manner highly
      recommends our selection strategy for any type of investigation where origin or
      target sequences of the sought-after sncRNAs are known.

PMID- 22458360
TI  - Flexural properties and shock-absorbing capabilities of new face guard materials
      reinforced with fiberglass cloth.
AB  - AIM:  Experimental materials incorporating fiberglass cloth were used to develop
      a thin and lightweight face guard (FG). This study aims to evaluate the effect of
      fiberglass reinforcement on the flexural and shock absorption properties compared
      with conventional thermoplastic materials. MATERIAL AND METHOD:  Four commercial
      3.2-mm and 1.6-mm medical splint materials (Aquaplast, Polyform, Co-polymer, and
      Erkodur) and two experimental materials were examined for use in FGs. The
      experimental materials were prepared by embedding two or four sheets of a plain
      woven fiberglass cloth on both surfaces of 1.5-mm Aquaplast. The flexural
      strength and flexural modulus were determined using a three-point bending test.
      The shock absorption properties were evaluated for a 5200-N impact load using the
      first peak intensity with a load cell system and the maximum stress with a film
      sensor system. RESULTS AND CONCLUSIONS:  The flexural strength (74.6 MPa) and
      flexural modulus (6.3 GPa) of the experimental material with four sheets were
      significantly greater than those of the 3.2-mm commercial specimens, except for
      the flexural strength of one product. The first peak intensity (515 N) and
      maximum stress (2.2 MPa) of the experimental material with four sheets were
      significantly lower than those of the commercial 3.2-mm specimens, except for one
      product for each property. These results suggest that the thickness and weight of
      the FG can be reduced using the experimental fiber-reinforced material.

PMID- 22458361
TI  - Chronic low back pain is associated with reduced vertebral bone mineral measures
      in community-dwelling adults.
AB  - BACKGROUND: Chronic low back pain (CLBP) experienced in middle-age may have
      important implications for vertebral bone health, although this issue has not
      been investigated as a primary aim previously. This study investigated the
      associations between CLBP and dual energy X-ray absorptiometry (DXA)-derived
      vertebral bone mineral measures acquired from postero-anterior and lateral
      projections, among community-dwelling, middle-aged adults. METHODS: Twenty-nine
      adults with CLBP (11 male, 18 female) and 42 adults with no history of LBP in the
      preceding year (17 male, 25 female) were evaluated. Self-reported demographic and
      clinical data were collected via questionnaires. Areal bone mineral density
      (aBMD) was measured in the lumbar spine by DXA. Apparent volumetric (ap.v) BMD in
      the lumbar spine was also calculated. Multiple linear regression models were used
      to examine associations between study group (CLBP and control) and vertebral DXA
      variables by gender, adjusting for height, mass and age. RESULTS: There was no
      difference between groups by gender in anthropometrics or clinical
      characteristics. In the CLBP group, the mean (SD) duration of CLBP was 13.3
      (10.4) years in males and 11.6 (9.9) years in females, with Oswestry Disability
      Index scores of 16.2 (8.7)% and 15.4 (9.1)%, respectively. Males with CLBP had
      significantly lower adjusted lateral-projection aBMD and lateral-projection
      ap.vBMD than controls at L3 with mean differences (standard error) of 0.09 (0.04)
      g/cm2 (p = 0.03) and 0.02 (0.01) g/cm3 (p = 0.04). These multivariate models
      accounted for 55% and 53% of the variance in lateral-projection L3 aBMD and
      lateral-projection L3 ap.vBMD. CONCLUSIONS: CLBP in males is associated with some
      lumbar vertebral BMD measures, raising important questions about the mechanism
      and potential clinical impact of this association.

PMID- 22458362
TI  - Investigation of rheological properties and conformation of silk fibroin in the
      solution of AmimCl.
AB  - The conformation and eventual morphology of silk fibroin (SF) chains are crucial
      for the mechanical properties of SF materials, and are strongly related to the
      solvation step as a key stage in their processing conditions. In this work, a
      novel SF/AmimCl (1-allyl-3-methylimidazolium chloride) solution with unique
      properties is reported and compared with conventional regenerated SF aqueous
      solutions, based on an investigation of its rheological properties. The steady
      shearing behavior suggested that AmimCl is a good solvent for SF molecules, and
      shear thinning of semidiluted SF/AmimCl solution at high shear rates showed
      behavior similar to that in native spinning, which is due to the rearrangement
      and orientation of SF molecular chains. Fitting of experimental dynamic
      viscoelastic data to the Rouse model provided an effective method to estimate the
      molecular weight of SF. We believe that this work not only provides a better
      understanding of the relationship between properties of silk protein and
      aggregation states of their molecular chains, but also provides tools to
      fabricate high-performance SF-based materials.

PMID- 22458363
TI  - Potentially avoidable hospitalizations of dually eligible Medicare and Medicaid
      beneficiaries from nursing facility and Home- and Community-Based Services waiver
      programs.
AB  - OBJECTIVES: Beneficiaries dually eligible for Medicare and Medicaid are of
      increasing interest because of their clinical complexity and high costs. The
      objective of this study was to examine the incidence, costs, and factors
      associated with potentially avoidable hospitalizations (PAH) in this population.
      DESIGN: Retrospective study of hospitalizations. SETTING: Hospitalizations from
      nursing facilities (NF) including Medicare and Medicaid-covered stays, and
      Medicaid Home and Community-Based Services (HCBS) waiver programs. PARTICIPANTS:
      Dually eligible individuals who received Medicare skilled nursing facility (SNF)
      or Medicaid NF services or HCBS waiver services in 2005. INTERVENTIONS: None.
      MEASUREMENTS: Potentially avoidable hospitalizations were defined by an expert
      panel that identified conditions and associated Diagnostic Related Groups (DRGs)
      which can often be prevented or safely and effectively managed without
      hospitalization. RESULTS: More than one-third of the population was hospitalized
      at least once, totaling almost 1 million hospitalizations. The admitting DRG for
      382,846 (39%) admissions were identified as PAH. PAH rates varied considerably
      among states, and blacks had a higher rate and costs for PAH than whites. Five
      conditions (pneumonia, congestive heart failure, urinary tract infections,
      dehydration, and chronic obstructive pulmonary disease/asthma) were responsible
      for 78% of the PAH. The total Medicare costs for these hospitalizations were $3
      billion, but only $463 million for Medicaid. A sensitivity analysis, assuming
      that 20%-60% of these hospitalizations could be prevented, revealed that between
      77,000 and 260,000 hospitalizations and between $625 million and $1.9 billion in
      expenditures could be avoided annually in this population. CONCLUSION:
      Potentially avoidable hospitalizations are common and costly in the dually
      eligible population. New initiatives are needed to reduce PAH in this population
      as they are costly and can adversely affect function and quality of life.

PMID- 22458364
TI  - Thermodynamics of fragment binding.
AB  - The ligand binding pockets of proteins have preponderance of hydrophobic amino
      acids and are typically within the apolar interior of the protein; nevertheless,
      they are able to bind low complexity, polar, water-soluble fragments. In order to
      understand this phenomenon, we analyzed high resolution X-ray data of protein
      ligand complexes from the Protein Data Bank and found that fragments bind to
      proteins with two near optimal geometry H-bonds on average. The linear extent of
      the fragment binding site was found not to be larger than 10 A, and the H-bonding
      region was found to be restricted to about 5 A on average. The number of
      conserved H-bonds in proteins cocrystallized with multiple different fragments is
      also near to 2. These fragment binding sites that are able to form limited number
      of strong H-bonds in a hydrophobic environment are identified as hot spots. An
      estimate of the free-energy gain of H-bond formation versus apolar desolvation
      supports that fragment sized compounds need H-bonds to achieve detectable
      binding. This suggests that fragment binding is mostly enthalpic that is in line
      with their observed binding thermodynamics documented in Isothermal Titration
      Calorimetry (ITC) data sets and gives a thermodynamic rationale for fragment
      based approaches. The binding of larger compounds tends to more rely on apolar
      desolvation with a corresponding increase of the entropy content of their binding
      free-energy. These findings explain the reported size-dependence of maximal
      available affinity and ligand efficiency both behaving differently in the small
      molecule region featured by strong H-bond formation and in the larger molecule
      region featured by apolar desolvation.

PMID- 22458366
TI  - Fortification of CdSe quantum dots with graphene oxide. Excited state
      interactions and light energy conversion.
AB  - Graphene based 2-D carbon nanostructures provide new opportunities to fortify
      semiconductor based light harvesting assemblies. Electron and energy transfer
      rates from photoexcited CdSe colloidal quantum dots (QDs) to graphene oxide (GO)
      and reduced graphene oxide (RGO) were isolated by analysis of excited state
      deactivation lifetimes as a function of degree of oxidation and charging in
      (R)GO. Apparent rate constants for energy and electron transfer determined for
      CdSe-GO composites were 5.5 * 10(8) and 6.7 * 10(8) s(-1), respectively.
      Additionally, incorporation of GO in colloidal CdSe QD films deposited on
      conducting glass electrodes was found to enhance the charge separation and
      electron conduction through the QD film, thus allowing three-dimensional
      sensitization. Photoanodes assembled from CdSe-graphene composites in quantum dot
      sensitized solar cells display improved photocurrent response (~150%) over those
      prepared without GO.

PMID- 22458365
TI  - Dramatic improvement in sexual function induced by intranasal oxytocin.
AB  - INTRODUCTION: A variety of sources indicate that oxytocin has beneficial effects
      on several components of sexuality. This is a case report on a male who had
      significant, broad-spectrum improvements in sexual function during a course of
      intranasal oxytocin treatment for social anxiety. AIM: To document a case of
      diverse, salutary effects of oxytocin on sexual function. METHODS: The patient
      was in individual treatment for a variety of difficulties, including social
      avoidance and relational problems. A biopsychosocial evaluation ruled out medical
      conditions and substance-related issues as a cause of sexual difficulties. After
      obtaining informed consent, an off-label trial of intranasal oxytocin was
      administered targeting his social anxiety and relational avoidance. RESULTS:
      Oxytocin positively impacted a number of components of sexual function, including
      libido, erection, and orgasm, and was well tolerated. CONCLUSIONS: This is the
      first case we are aware of documenting broad-spectrum benefits of chronic
      intranasal oxytocin on male sexual function. Future trials of oxytocin for
      psychiatric indications should specifically monitor its effects on sexuality, and
      trials directly investigating oxytocin's impact on aspects of sexual function are
      warranted.

PMID- 22458367
TI  - Nonprecious metal catalysts for fuel cell applications: electrochemical dioxygen
      activation by a series of first row transition metal tris(2-pyridylmethyl)amine
      complexes.
AB  - A series of divalent first row triflate complexes supported by the ligand tris(2
      pyridylmethyl)amine (TPA) have been investigated as oxygen reduction catalysts
      for fuel cell applications. [(TPA)M(2+)](n+) (M = Mn, Fe, Co, Ni, and Cu)
      derivatives were synthesized and characterized by X-ray crystallography, cyclic
      voltammetry, NMR spectroscopy, magnetic susceptibility, IR spectroscopy, and
      conductance measurements. The stoichiometric and electrochemical O(2)
      reactivities of the series were examined. Rotating-ring disk electrode (RRDE)
      voltammetry was used to examine the catalytic activity of the complexes on a
      carbon support in acidic media, emulating fuel cell performance. The iron complex
      displayed a selectivity of 89% for four-electron conversion and demonstrated the
      fastest reaction kinetics, as determined by a kinetic current of 7.6 mA.
      Additionally, the Mn, Co, and Cu complexes all showed selective four-electron
      oxygen reduction (<28% H(2)O(2)) at onset potentials (~0.44 V vs RHE) comparable
      to state of the art molecular catalysts, while being straightforward to access
      synthetically and derived from nonprecious metals.

PMID- 22458368
TI  - Effect of NT-pro-BNP assay on accuracy and confidence of general practitioners in
      diagnosing heart failure or respiratory disease in cats with respiratory signs.
AB  - BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) can distinguish
      congestive heart failure (CHF) from primary respiratory disease in cats with
      respiratory signs with approximately 90% diagnostic accuracy, but the additive
      benefit of NT-proBNP to improve the diagnosis obtained from conventional testing
      in individual cases remains unknown. HYPOTHESIS: NT-proBNP will improve the
      diagnostic accuracy and confidence of general practice veterinarians in assessing
      cats with respiratory signs. ANIMALS: Ten cats with respiratory signs. METHODS:
      History, physical examination, thoracic radiographs, electrocardiogram (ECG), and
      biochemical analysis of 10 cats presented to the University of Pennsylvania or
      Tufts University with a history of respiratory signs were evaluated by 50 general
      practice veterinarians using an online survey tool. Participants were asked to
      provide (1) diagnosis of CHF or primary respiratory disease, and (2) level of
      confidence in their diagnosis (1, lowest to 10, highest) before and after
      disclosure of NT-proBNP results. Diagnoses (CHF, n = 5; primary respiratory, n =
      5) were compared to the gold standard defined as consensus opinion of 3 board
      certified cardiologists blinded to the NT-proBNP results. RESULTS: Overall
      correctness of the practitioners was 69.2%, and significantly increased after
      practitioners were provided NT-proBNP results (87.0%, P = .0039). Median
      practitioner confidence before NT-proBNP disclosure was 6 (IQR, 5-8) and
      significantly increased after disclosure (8; IQR, 6-10; P = .0039). CONCLUSIONS:
      These data indicate a relatively low accuracy and level of confidence in the
      diagnosis of feline respiratory signs. Use of NT-proBNP assay in conjunction with
      conventional evaluation by general practitioners significantly improved their
      diagnostic accuracy and confidence.

PMID- 22458370
TI  - Lessons and opportunities from autism screening in high-risk children.

PMID- 22458369
TI  - Synthesis of 4-substituted chlorophthalazines, dihydrobenzoazepinediones, 2
      pyrazolylbenzoic acid, and 2-pyrazolylbenzohydrazide via 3-substituted 3
      hydroxyisoindolin-1-ones.
AB  - Herein we describe a general three-step synthesis of 4-substituted
      chlorophthalazines in good overall yields. In the key step, N,N
      dimethylaminophthalimide (8a) directs the selective monoaddition of alkyl, aryl,
      and heteroaryl organometallic reagents to afford 3-substituted 3
      hydroxyisoindolinones 9b, 9i-9am. Many of these hydroxyisoindolinones are
      converted to chlorophthalazines 1b-1v via reaction with hydrazine, followed by
      chlorination with POCl(3). We have also discovered two novel transformations of 3
      vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic
      reagents to N,N-dimethylaminophthalimide (8a) provided dihydrobenzoazepinediones
      15a-15c via the proposed ring expansion of 3-vinyl-3-hydroxyisoindolinone
      intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and
      substituted hydrazines to afford 2-pyrazolyl benzoic acids 16a-16d and 2
      pyrazolyl benzohydrazides 17a-17g rather than the expected alkynyl
      phthalazinones.

PMID- 22458371
TI  - Rattle-type carbon-alumina core-shell spheres: synthesis and application for
      adsorption of organic dyes.
AB  - Porous micro- and nanostructured materials with desired morphologies and tunable
      pore sizes are of great interests because of their potential applications in
      environmental remediation. In this study, novel rattle-type carbon-alumina core
      shell spheres were prepared by using glucose and metal salt as precursors via a
      simple one-pot hydrothermal synthesis followed by calcination. The
      microstructure, morphology, and chemical composition of the resulting materials
      were characterized by X-ray diffraction (XRD), energy dispersive X-ray
      spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and N(2) adsorption-desorption techniques. These rattle-type
      spheres are composed of a porous Al(2)O(3) shell (thickness ~ 80 nm) and a solid
      carbon core (diameter ~ 200 nm) with variable space between the core and shell.
      Furthermore, adsorption experiments indicate that the resulting carbon-alumina
      particles are powerful adsorbents for the removal of Orange-II dye from water
      with maximum adsorption capacity of ~210 mg/g. It is envisioned that these rattle
      type composite particles with high surface area and large cavities are of
      particular interest for adsorption of pollutants, separation, and water
      purification.

PMID- 22458373
TI  - Kisspeptin-immunoreactivity changes in a sex- and hypothalamic-region-specific
      manner across rat postnatal development.
AB  - Kisspeptins are potent secretagogues of gonadotrophin-releasing hormone, playing
      a key role in puberty onset. These peptides are produced by distinct neuronal
      populations of the hypothalamus located in the rostral periventricular area of
      the third ventricle (RP3V) and arcuate nucleus (ARC). The present
      immunohistochemical study aimed to determine the spatiotemporal onset of
      kisspeptin-immunoreactivity (-IR) in the neonatal hypothalamus of male and female
      rats and to evaluate changes in kisspeptin-IR around puberty. Kisspeptin-IR cells
      and fibres could be detected from the day of birth in the ARC of both males and
      females. At this stage, only females displayed some kisspeptin-IR fibres in the
      RP3V. From postnatal day 7 to adulthood, males displayed lower levels of
      kisspeptin-IR than females in both regions. During infancy, kisspeptin-IR fibre
      density in the female decreased in the ARC, whereas it increased in the RP3V. A
      sex-independent decline in RP3V kisspeptin-IR fibre density was observed in the
      juvenile, followed by a peripubertal increase in RP3V and ARC kisspeptin-IR.
      These peripubertal increases in kisspeptin-IR occurred at different timings
      dependent on sex and region. In females specifically, the increase in kisspeptin
      IR fibre density occurred first in the ARC and later in the RP3V under constant
      levels of circulating oestradiol. In conclusion, the present study highlights the
      expression of hypothalamic kisspeptins soon after birth, as well as the neonatal
      establishment of a strong and persisting sex difference in ARC kisspeptin-IR in
      rats. Moreover, a female-specific desynchronisation of the ARC and RP3V was
      observed with respect to the increase in kisspeptin-IR fibre density around
      puberty, which was not related to peripubertal variations in circulating
      oestradiol.

PMID- 22458372
TI  - Delays in auditory processing identified in preschool children with FASD.
AB  - BACKGROUND: Both sensory and cognitive deficits have been associated with
      prenatal exposure to alcohol; however, very few studies have focused on sensory
      deficits in preschool-aged children. As sensory skills develop early,
      characterization of sensory deficits using novel imaging methods may reveal
      important neural markers of prenatal alcohol exposure. METHODS: Participants in
      this study were 10 children with a fetal alcohol spectrum disorder (FASD) and 15
      healthy control (HC) children aged 3 to 6 years. All participants had normal
      hearing as determined by clinical screens. We measured their neurophysiological
      responses to auditory stimuli (1,000 Hz, 72 dB tone) using magnetoencephalography
      (MEG). We used a multidipole spatio-temporal modeling technique to identify the
      location and timecourse of cortical activity in response to the auditory tones.
      The timing and amplitude of the left and right superior temporal gyrus sources
      associated with activation of left and right primary/secondary auditory cortices
      were compared across groups. RESULTS: There was a significant delay in M100 and
      M200 latencies for the FASD children relative to the HC children (p = 0.01), when
      including age as a covariate. The within-subjects effect of hemisphere was not
      significant. A comparable delay in M100 and M200 latencies was observed in
      children across the FASD subtypes. CONCLUSIONS: Auditory delay revealed by MEG in
      children with FASDs may prove to be a useful neural marker of information
      processing difficulties in young children with prenatal alcohol exposure. The
      fact that delayed auditory responses were observed across the FASD spectrum
      suggests that it may be a sensitive measure of alcohol-induced brain damage.
      Therefore, this measure in conjunction with other clinical tools may prove useful
      for early identification of alcohol affected children, particularly those without
      dysmorphia.

PMID- 22458374
TI  - Directed orientation of asymmetric composite dumbbells by electric field induced
      assembly.
AB  - Assembly and directed orientation of anisotropic particles with an external ac
      electric field in a range from 1 kHz to 2 MHz were studied for asymmetric
      composite dumbbells incorporating a silica, titania, or titania/silica
      (titania:silica = 75:25 vol %) sphere. The asymmetric composite dumbbells, which
      were composed of a polymethylmethacrylate (PMMA)-coated sphere (core-shell part)
      and a polystyrene (PSt) lobe, were synthesized with a soap-free emulsion
      polymerization to prepare PMMA-coated inorganic spheres and another soap-free
      emulsion polymerization to form a polystyrene (PSt) lobe from the PMMA-coated
      inorganic spheres. The composite dumbbells dispersed in water were directly
      observed with optical microscopy. The dumbbells incorporating a silica sphere
      oriented parallel to an electric field in the whole frequency range and they
      formed a pearl chain structure at a high frequency of 2 MHz. The titania
      incorporated dumbbells formed chain structures, in which they contacted their
      core-shell parts and oriented perpendicularly to a low-frequency (kHz) field,
      whereas they oriented parallel to a high-frequency (MHz) field. Since the
      alignment of dumbbells in the chains depends not only on the interparticle forces
      but also on the torque that the induced dipoles in the dumbbells experience in
      the electric field, the orientation of dumbbells perpendicular to the electric
      field was the case dominated by the interparticle force, whereas the other
      orientation was the case dominated by the torque. The present experiments show
      that the incorporation of inorganic dumbbells is an effective way to control the
      assembled structure and orientation with an electric field. 

PMID- 22458375
TI  - A pilot study of the effects of internet-based cognitive stimulation on
      neuropsychological function in HIV disease.
AB  - PURPOSE: Mild cognitive deficits associated with HIV disease can affect
      activities of daily living, so interventions that reduce them may have a long
      term effect on quality of life. We evaluated the feasibility of a cognitive
      stimulation program (CSP) to improve neuropsychological test performance in HIV
      disease. METHODS: Sixty volunteers (30 HIV-infected) participated. The primary
      outcome was the change in neuropsychological test performance as indexed by the
      Global Impairment Rating; secondary outcomes included mood (Brief Symptom
      Inventory subscales) and quality of life rating (Medical Outcomes Survey-HIV)
      scales. RESULTS: Fifty-two participants completed all 24 weeks of the study, and
      54% of the participants in the CSP group successfully used the system via
      internet access from their home or other location. There was a significant
      interaction between usage and study visit such that the participants who used the
      program most frequently showed significantly greater improvements in cognitive
      functioning (F(3, 46.4 = 3.26, p = 0.030); none of the secondary outcomes were
      affected by the dose of CSP. CONCLUSIONS: We found it possible to complete an
      internet-based CSP in HIV-infected individuals; ease of internet access was a key
      component for success. Participants who used the program most showed improvements
      in cognitive function over the 24-week period, suggesting that a larger clinical
      trial of CSP may be warranted.

PMID- 22458376
TI  - Differential patterns of connectivity in progressive mild cognitive impairment.
AB  - It is now widely accepted that Alzheimer's disease is characterized by a
      functional disconnection between brain regions. The disease appears to begin up
      to decades prior to clinical diagnosis. Therefore, in the present study, we
      combined magnetoencephalography, a memory task, and functional connectivity
      analysis in mild cognitive impairment subjects in order to identify functional
      connectivity patterns that could characterize subjects who would eventually go on
      to develop the disease. We monitored 19 subjects and finally 5 of them developed
      Alzheimer's disease. These progressive patients showed a differential profile of
      functional connectivity values compared with those patients who remained stable
      over time. Specifically there were higher synchronization values over the parieto
      occipital region in alpha and beta frequency bands. The involvement of this brain
      region in amyloid-beta accumulation and its possible association with hyper
      synchronization are also discussed.

PMID- 22458377
TI  - Nanoaggregates of biodegradable amphiphilic random polycations for delivering
      water-insoluble drugs.
AB  - Cationic amphiphilic random copolyesters were obtained by copolymerization of 5-Z
      amino-delta-valerolactone and epsilon-caprolactone. The amino content of the
      final copolymers was controlled by the polymerization feed ratio and was in the
      range 10 to 100%. Copolymers solubility and aggregation behavior was assessed by
      conductometric and zeta potential analyses. A critical aggregation concentration
      of ca. 0.05% (w/v) was found for all water-soluble copolymers that formed
      nanoaggregates. Two populations were found to be present in equilibrium with
      hydrodynamic diameters in the range of 30-50 and 100-250 nm. The capacity to use
      the amphiphilic and cationic character of the nanoaggregates to encapsulate
      highly hydrophobic compounds was further investigated. Finally, copolymers hemo-
      and cytocompatibility were evaluated by hemagglutination, hemolysis, and cells
      proliferation tests. The results showed that the proposed cationic amphiphilic
      random copolyesters are biocompatible.

PMID- 22458378
TI  - Protein phosphorylation in encystment-induced Colpoda cucullus: localization and
      identification of phosphoproteins.
AB  - In Colpoda cucullus, the morphogenetic transformation was preceded by an
      enhancement of the in vivo protein phosphorylation level. Immunofluorescence
      microscopy using antiphosphoserine antibody showed that these phosphorylated
      proteins were localized in the macronucleus and other cytoplasmic regions.
      Biotinylated Phos-tag/ECL assays of isolated macronuclei showed that a 33-kDa
      protein (p33) was localized within them. The p33 obtained from isolated
      macronuclei was tentatively identified as ribosomal P0 protein by LC-MS/MS
      analysis. In addition, among the encystment-specific phosphoproteins obtained by
      phosphate-affinity chromatography, the 29-, 31-, and 33-kDa proteins (p29, p31,
      and p33) were tentatively identified as ribosomal P0 protein, whereas the 24-kDa
      phosphoprotein (p24) was tentatively identified as ribosomal S5 protein.

PMID- 22458380
TI  - The AJT report: news and issues that affect organ and tissue transplantation. A
      maze of information.

PMID- 22458379
TI  - Response gene to complement-32 enhances metastatic phenotype by mediating
      transforming growth factor beta-induced epithelial-mesenchymal transition in
      human pancreatic cancer cell line BxPC-3.
AB  - BACKGROUND: Response gene to complement-32 (RGC-32) is comprehensively expressed
      in many kinds of tissues and has been reported to be expressed abnormally in
      different kinds of human tumors. However, the role of RGC-32 in cancer remains
      controversial and no reports have described the effect of RGC-32 in pancreatic
      cancer. The present study investigated the expression of RGC-32 in pancreatic
      cancer tissues and explored the role of RGC-32 in transforming growth factor-beta
      (TGF-beta)-induced epithelial-mesenchymal transition (EMT) in human pancreatic
      cancer cell line BxPC-3. METHODS: Immunohistochemical staining of RGC-32 and E
      cadherin was performed on specimens from 42 patients with pancreatic cancer, 12
      with chronic pancreatitis and 8 with normal pancreas. To evaluate the role of RGC
      32 in TGF-beta-induced EMT in pancreatic cancer cells, BxPC-3 cells were treated
      with TGF-beta1, and RGC-32 siRNA silencing and gene overexpression were performed
      as well. The mRNA expression and protein expression of RGC-32 and EMT markers
      such E-cadherin and vimentin were determined by quantitative reverse
      transcription-PCR (qRT-PCR) and western blot respectively. Finally, migration
      ability of BxPC-3 cells treated with TGF-beta and RGC-32 siRNA transfection was
      examined by transwell cell migration assay. RESULTS: We found stronger expression
      of RGC-32 and higher abnormal expression rate of E-cadherin in pancreatic cancer
      tissues than those in chronic pancreatitis tissues and normal pancreatic tissues.
      Immunohistochemical analysis revealed that both RGC-32 positive expression and E
      cadherin abnormal expression in pancreatic cancer were correlated with lymph node
      metastasis and TNM staging. In addition, a significant and positive correlation
      was found between positive expression of RGC-32 and abnormal expression of E
      cadherin. Furthermore, in vitro, we found sustained TGF-beta stimuli induced EMT
      and up-regulated RGC-32 expression in BxPC-3 cells. By means of siRNA silencing
      and gene overexpression, we further demonstrated that RGC-32 mediated TGF-beta
      induced EMT and migration in BxPC-3 cells. CONCLUSIONS: The results above
      indicated that RGC-32 might be a novel metastasis promoting gene in pancreatic
      cancer and it enhances metastatic phenotype by mediating TGF-beta-induced EMT in
      human pancreatic cancer cell line BxPC-3.

PMID- 22458381
TI  - Literature watch: implications for transplantation. AHR and tryptophan
      catabolism: putting the effector T-cell response to sleep.

PMID- 22458382
TI  - Truth and consequences: the challenge of greater transparency in liver
      distribution and utilization.

PMID- 22458384
TI  - Tongue ulcer in a liver transplant recipient on a new immunosuppressive regimen.

PMID- 22458385
TI  - An investigation of striae distensae using reflectance confocal microscopy.
AB  - BACKGROUND:   Striae distensae, otherwise known as stretch marks, are white or
      red scar-like streaks on the skin. Although they are not associated with adverse
      health outcomes, striae are associated with significant cosmetic morbidity. While
      they have been well characterised histopathologically, a non-invasive method of
      microscopic lesion assessment of striae would be welcome. METHODS:   To gain
      insight into the small-scale morphological features associated with striae we
      undertook an in vivo investigation of nine patients with striae alba and one with
      striae rubra utilising reflectance confocal microscopy (RCM). RESULTS:   Here we
      demonstrate that features known to be present using light microscopy, such as
      parallel collagen bundles in the dermis, and some features that are not well
      recognised by light microscopy, including distortion of dermal papillae, are
      demonstrable using RCM. CONCLUSIONS:   Characterising the features of early and
      established striae distensae with confocal microscopy is an important foundation
      for future work. The potential ability to reliably identify the earliest
      pathological changes in skin in early lesions or before clinically manifest
      striae develop--a task facilitated by our findings--will increase the
      understanding of their pathogenesis and will have significant practical utility
      in monitoring the impact of future preventative interventions.

PMID- 22458386
TI  - Double-blind, within-patient, randomized, clinical trial comparing fluorine
      synthetic fiber socks with standard cotton socks in improving plantar psoriasis.
AB  - BACKGROUND: Rubbing the skin and trauma may influence the persistence of
      psoriasis over time. OBJECTIVES: To assess the impact of a new fabric made with a
      special fluorine-synthetic fiber in improving plantar psoriasis. METHODS: A total
      of 20 patients with symmetrical lesions were randomized to receive on one side a
      sock made of fluorine-synthetic fiber and on the other side a sock made of cotton
      fabric for 4 weeks. The main outcome was the percentage reduction of lesional
      area. RESULTS: In an intention-to-treat analysis, the median lesion reduction was
      11.95% in fluorine-synthetic fiber arm and 11.89% in cotton arm (p = 0.776).
      Among secondary outcomes, patient global satisfaction showed a statistically
      significant median score of 32 toward fluorine-synthetic fiber arm (p = 0.011).
      CONCLUSION: In spite of our main negative results, it is important to continue
      investigating on the relation between textiles and skin disorders to improve
      patient well-being.

PMID- 22458387
TI  - Mixed-valent uranium(IV,VI) diphosphonate: synthesis, structure, and
      spectroscopy.
AB  - A mixed-valent uranium(IV,VI) diphosphonate,
      (H(3)O)(2)(UO(2))(3)U(H(2)O)(2)[CH(2)(PO(3))(2)](3).6H(2)O (UC1P2S), has been
      synthesized under hydrothermal conditions. S-2-butanol was used to reduce uranium
      VI to IV. The tetravalent uranium centers adopt eight-coordinate geometries,
      while hexavalent uranyl units are all tetragonal bipyramids. The UV-vis-NIR
      spectrum of UC1P2S shows absorption features for both U(VI) and U(IV).

PMID- 22458389
TI  - Geriatric nutritional risk index may be a significant predictor of mortality in
      Korean hemodialysis patients: a single center study.
AB  - Our objective was to examine the association between the Geriatric Nutritional
      Risk Index (GNRI) and mortality in Korean hemodialysis (HD) patients. We examined
      the GNRI of 120 maintenance HD patients and followed these patients for 120
      months. Predictors for all-cause death were examined using life table analysis
      and the Cox proportional hazards model. Life table analysis revealed that
      subjects with a GNRI < 90 (n = 19) had a marginally lower survival rate than did
      those with a GNRI >= 90 (n = 101) (Wilcoxon test, P = 0.048). Multivariate Cox
      proportional hazards analyses demonstrated that the GNRI was a significant
      predictor of mortality (hazard ratio 0.966, 95% confidence interval 0.945-0.995,
      P = 0.018), after adjusting for age, sex, presence of diabetes mellitus, and body
      weight. These results demonstrate that the GNRI may be a significant predictor of
      mortality in Korean HD patients.

PMID- 22458388
TI  - Late dialysis start did not affect long-term outcome in Japanese dialysis
      patients: long-term prognosis from Japanese Society for [corrected] Dialysis
      Therapy Registry.
AB  - Early initiation of dialysis had been considered one of the most important
      methods for better prognosis of dialysis patients. One of the reasons for this
      was that long-term as well as short-term prognosis was poor with late initiation
      of dialysis. In this study, we analyzed the effects of residual renal function
      and comorbidity on both short- and long-term outcomes of ESRD patients. The
      subjects of this study were 20 854 patients who started renal replacement therapy
      (RRT) in 1989 and 1990, when we conducted national surveillance for new ESRD
      patients. The effects of glomerular filtration rate (GFR) at dialysis start and
      comorbidity conditions on survival were measured. Mortality hazard ratio (HR) was
      calculated using a Cox proportional hazard model. Multivariate analysis included
      pre-dialysis estimated GFR, age, sex, and underlying renal disease. The mean age
      of the subjects was 57.7 years old. Mean GFR at dialysis initiation was 5.00
      mL/min per 1.73 m(2) and GFR was significantly higher in patients with diabetes.
      The median survival time from the start of dialysis was 69 months, excluding
      subjects who died within 3 months; 1-year survival was 89.7%, while 2-year, 3
      year, 5-year, 10-year, and 15-year cumulative survival rates were 79.3%, 71.1%,
      57.8%, 37.3%, and 26.1%, respectively. For mortality risks, the higher the GFR at
      dialysis initiation, the worse the HR for mortality in both short-term and long
      term prognoses by unadjusted analysis. However, after adjustments for age,
      gender, underlying renal diagnosis, and symptom at dialysis initiation, both late
      and early initiation of RRT did not affect long-term prognosis.

PMID- 22458390
TI  - Elemental concentrations in scalp hair, nutritional status and health-related
      quality of life in hemodialysis patients.
AB  - Elemental concentrations in hair from hemodialysis (HD) patients have not been
      well investigated. We examined the relationships between the elemental
      concentrations in scalp hair and health-related quality of life (HRQOL) and
      nutritional status in HD patients. Twenty six elemental concentrations were
      measured in scalp hair samples from 60 male HD patients using inductively-coupled
      plasma mass spectrometry. To evaluate HRQOL, the Short Form 36 item health survey
      (SF36) was used. As indices of nutritional status, body mass index, serum
      parameters, and geriatric nutritional risk index (GNRI) were used. Phosphorus
      correlated positively with serum creatinine, blood urea nitrogen (BUN), GNRI and
      the physical domains of the SF36. Zinc correlated positively with serum
      creatinine, BUN and the physical domains of the SF36. Mercury and arsenic
      correlated positively with BUN. Cadmium correlated negatively with serum albumin,
      BUN and GNRI. Copper correlated positively with the physical domains of the SF36.
      Iodine correlated negatively with the physical domains of the SF36. Selenium
      correlated negatively with the mental domains of the SF36. In conclusion,
      phosphorus and zinc concentrations in scalp hair can be additional biomarkers of
      HRQOL and/or nutritional status in HD patients. Cadmium accumulation correlated
      with malnutrition. Iodine and selenium accumulation may adversely affect HRQOL.
      Further investigation is necessary to determine precisely how these elements
      affect these measures.

PMID- 22458391
TI  - Left ventricular end-diastolic diameter is an independent predictor of mortality
      in hemodialysis patients.
AB  - Left ventricular (LV) function is impaired in most hemodialysis (HD) patients. We
      conducted an observational cohort study to investigate whether LV end-diastolic
      diameter (LVDd) could predict all-cause mortality in a cohort of 166 HD patients.
      The LVDd values (5.06 +/- 0.64 cm) of the non-survivor group were significantly
      greater than in the survivor group (4.78 +/- 0.71 cm). The area under the
      receiver operating characteristic curve for an LVDd cut-off value of 5.01 cm was
      0.6145 (P = 0.0234). The sensitivity and specificity of the LVDd threshold of
      5.01 cm were 75.7% and 50.4%, respectively. The 4-year survival rate was
      significantly lower in the group with LVDd >= 5.01 cm than in the group with LVDd
      < 5.01 cm (log-rank test, P = 0.0047). Multivariate analysis with adjustments for
      clinical and echocardiographic parameters showed that increased LVDd was an
      independent predictor of all-cause mortality (hazard ratio 2.363, 95% CI 1.320
      4.228, P = 0.0013). The results of the present study showed that increased LVDd
      predicts the all-cause mortality of chronic HD patients better than other
      echocardiographic parameters. Our findings suggest that LVDd measurements may be
      helpful for risk stratification and providing therapeutic direction for the
      management of HD patients.

PMID- 22458392
TI  - Zinc sulfate for relief of pruritus in patients on maintenance hemodialysis.
AB  - Pruritus is a common complaint in patients undergoing maintenance hemodialysis.
      The pathophysiology of pruritus in these patients is not well known, but the role
      of histamine release from mast cells has been reported. According to the
      inhibitory effects of zinc on histamine release and reported low levels of serum
      zinc in hemodialysis patients, we aimed to evaluate the effects of zinc sulfate
      for the relief of pruritus in these patients. This double-blind, randomized,
      placebo-controlled trial was conducted on 40 adults with end stage renal disease
      (ESRD) who were on maintenance hemodialysis in two university hospitals in
      Isfahan, Iran. Patients were randomized to receive either zinc sulfate (440
      mg/day) or placebo for two consecutive months. Pruritus was assessed at baseline
      and then every two weeks using a numerical rating scale from 0 to 10 until one
      month after treatment. Drug side effects were also assessed along with pruritus.
      There were 40 patients with a mean age of 55.5 +/- 15.2 (72.5% male) who
      completed the study. The two groups were similar in baseline characteristics.
      Pruritus was decreased in both groups after treatment but there was a
      significantly greater decrease in the zinc sulfate group compared with placebo (P
      = 0.018). Patient compliance was good and no severe side effects were observed.
      Zinc sulfate (440 mg/day) is more effective than placebo for the relief of
      pruritus in patients under maintenance hemodialysis. Further studies with larger
      sample size, longer treatment duration and follow-up and with various dosages of
      zinc sulfate are recommended.

PMID- 22458393
TI  - Low molecular weight iron dextran increases fibroblast growth factor-23
      concentration, together with parathyroid hormone decrease in hemodialyzed
      patients.
AB  - Fibroblast growth factor (FGF)-23 inhibits PTH production. Elevated FGF-23 and
      parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients.
      Iron polymaltose was shown to increase FGF-23 concentration. The effect of
      intravenous low molecular weight iron dextran (LMID) on these hormones and bone
      metabolism has not been studied in hemodialysis (HD). Twelve HD patients were
      prospectively followed up for 3 weeks after a single infusion of LMID. Calcium,
      phosphate, FGF-23, PTH, degradation products of C-terminal telopeptides of type I
      collagen (CTX) and procollagen I N-terminal propeptide (PINP) were measured prior
      to, and at week 1 and week 3 after the LMID administration. FGF-23 increased
      significantly from 453.4 (68.6-3971.5) pg/mL at baseline to 971.8 (779.5-3361.4)
      pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at
      week 3. The changes were accompanied by a significant decline in PTH from 367.6
      (21.4-1487.4) pg/mL at baseline to 315.7 (16.4-1339.8) pg/mL (P = 0.018) at week
      1 and subsequently began to increase toward the initial values. Phosphate,
      calcium, CTX and PINP did not change over the study course. LMID causes an
      increase in FGF-23 concentration together with a decrease in PTH. Our study
      highlights a pathophysiological element, which may connect suppression of
      parathyroid glands with intravenous iron supplementation.

PMID- 22458394
TI  - A model to predict optimal dialysate flow.
AB  - Diffusive clearance depends on blood (Qb) and dialysate flow (Qd) rates and the
      overall mass transfer area coefficient (KoA) of the dialyzer. In this article we
      describe a model to predict an appropriated AutoFlow (AF) factor (AF factor =
      Ratio Qd/Qb), that is able to provide adequate Kt/V for hemodialysis patients
      (HDP), while consuming lower amounts of dialysate, water and energy during the
      treatment. We studied in vivo the effects of three various Qd on the delivered
      dose of dialysis in 33 stable HDP. Hemodialysis was performed at Qd of 700 mL/mn,
      500 mL/mn, and with AF, whereas specific dialysis prescriptions (treatment time,
      blood flow rate [Qb], and type and size of dialyzer) were kept constant. The
      results showed that increasing the dialysate flow rate more than the model of AF
      predicted had a small effect on the delivered dose of dialysis. The Kt/V (mean +/
      SD) was 1.52 +/- 0.16 at Qd 700, 1.50 +/- 0.16 at Qd 500, and 1.49 +/- 0.15 with
      AF. The use of the AF function leads to a significant saving of dialysate fluid.
      The model predicts the appropriate AF factor that automatically adjusts the
      dialysate flow rate according to the effective blood flow rate of the patient to
      achieve an appreciable increase in dialysis dose at the lowest additional cost.

PMID- 22458395
TI  - Effect of heparin on conformation of the beta2-microglobulin molecule.
AB  - Heparin, one of the essential molecules called glycosaminoglycans (GAGs), is the
      anticoagulant that is commonly used in regular hemodialysis, during which
      dialysis-related amyloidosis (DRA) may develop. The pathogenic protein, i.e.
      precursor protein, in DRA is beta(2)-microglobulin (beta(2)m). Recent studies
      defined amyloidosis as a protein misfolding disease of precursor proteins
      including beta(2)m. Because the analytic technique capillary electrophoresis can
      identify molecular variants of the folded beta(2)m, i.e. conformational variants,
      we utilized it to investigate the effect of heparin on beta(2)m conformation and
      thus determined whether heparin can promote DRA development by inducing a
      conformational change in the amyloidogenic beta(2)m molecule. Heparin had a
      slight but significant effect on intermediate beta(2)m conformation but no effect
      on native beta(2)m conformation and on conversion of native to intermediate
      beta(2)m. Our findings thus suggest a possible association of beta(2)m with GAGs
      containing a sulfate moiety, including heparin, in HD patients.

PMID- 22458396
TI  - Renal replacement therapy in cardiology wards: changing trends in a transitional
      country.
AB  - The leading causes of death in patients with chronic kidney disease (CKD) are
      cardiovascular diseases, regardless of the stage of disease or method of renal
      replacement therapy. On the other hand, CKD is a major risk factor for
      cardiovascular complications after acute myocardial infarction, as well as for
      adverse outcome in patients with chronic heart failure. In the present study we
      prospectively followed-up nephrological interventions in cardiology wards in
      order to determine changes in indications, treatment possibilities and outcome of
      patients. All patients treated at cardiology ward of the Clinical Hospital Centre
      Zagreb and requiring renal replacement therapy from January 2003 to December 2009
      were included in the investigation. Cardiology hospital unit (intensive care or
      regular hospital cardiology ward), age, gender, Sepsis-related Organ Failure
      Assessment (SOFA) score, indication for dialysis, primary diagnosis, vascular
      access, methods of treatment, number of treatments, prescribed and delivered dose
      of dialysis and outcome were recorded. Patients were followed up until death
      during hospitalization or discharge from the hospital. From January 2003 to
      December 2009, 251 patients had been hospitalized at different cardiology wards
      and required renal replacement therapy. Mean age was 64.95 years (range 22 to 97
      years), and there were 27.8% female patients. 52.9% of patients were hospitalized
      in the coronary intensive care unit. SOFA score had increased during the observed
      period from average 6.5 in 2003 to 13.45 in 2009. Specific knowledge with close
      collaboration between nephrologists and cardiologists is needed to achieve
      optimal outcome in this complex condition.

PMID- 22458397
TI  - Systematic evaluation of vascular access by color-Doppler ultrasound decreased
      the incidence of emergent vascular access intervention therapy and X-ray exposure
      time: a single-center observational study.
AB  - Arteriovenous fistula has superior patency over other accesses, but vascular
      access intervention therapy (VAIVT) for stenosis or thrombosis still remain major
      reasons for hospital admission of dialysis patients. The aim of this study was to
      examine the usefulness of systematic evaluation of vascular access by color
      Doppler ultrasound (CDUS). This study was a single-center observational design
      study. We planned screening CDUS to evaluate all vascular accesses once per year,
      and additionally, follow-up CDUS of post-interventional patients 1 month, 3
      months and 6 months after their recent VAIVT. This systematic evaluation was
      started from September 2009. The observational period between September 2008 and
      August 2009 was defined as period A. The observational period between September
      2009 and August 2010 was defined as period B. We compared the incidence of
      emergent VAIVT and X-ray exposure time during the period A to B. 131 patients
      with AV fistula were assigned. 13 patients were excluded due to death, hospital
      transfer or re-operation of their accesses. During period A, 57 VAIVTs were
      carried out, and 37 cases (65%) were emergent. During period B, 42 VAIVTs were
      carried out, and 11 cases (25%) were emergent. The incidence of emergent
      intervention therapy was lower during period B than period A (P < 0.001). The
      amount of X-ray exposure time per patient was decreased in patients who received
      VAIVT during both periods (P < 0.03). Systematic evaluation of vascular access by
      CDUS decreased the incidence of emergent VAIVT and X-ray exposure time.

PMID- 22458398
TI  - Effects of peripheral blood mononuclear cells morphology on vascular
      calcification in uremic patients on maintenance hemodialysis.
AB  - We used high-resolution atomic force microscopy (AFM) to examine possible changes
      in the morphology of peripheral blood mononuclear cells (PBMCs), and to
      investigate their influence on vascular calcification in uremic patients on
      maintenance hemodialysis (MHD). 36 uremic patients had cardiovascular diseases
      after MHD (MHD group1) and 30 uremic patients did not (MHD group 2), and 20
      healthy volunteers were the control group. The extent of coronary artery
      calcification was assessed with coronary artery calcification score (CACS). AFM
      was used to analyze PBMCs nuances. Concentrations of bone morphogenetic protein-2
      (BMP-2) in PBMC supernatants were detected by ELISA. Protein expressions of BMP-2
      were measured by Western blot. No significant differences in PBMC morphology were
      observed among groups by light microscopy. AFM images revealed that uremic
      patients exhibited significant differences of PBMC morphology and vascular
      calcification when compared with healthy volunteers. The PBMCs in uremic patients
      were larger in volume, mean height, half-maximum amplitude, average roughness and
      higher concentrations and expression of BMP-2 and CACS (P < 0.05), with granular
      processes or caveolae of uneven size distributed over cell surfaces. These
      differences were also significant between MHD group 1 and group 2 (P < 0.05).
      PBMC volume, mean height, half-maximum amplitude, and average roughness were
      positively correlated with BMP-2 and CACS. Moreover, the correlation PBMC with
      BMP-2 was higher than with CACS. PBMC morphology in MHD patients was related to
      the degree of vascular calcification. The larger mean height, half-maximum
      amplitude, average roughness and cell volume were, the higher degree of vascular
      calcification was.

PMID- 22458399
TI  - Cardiovascular protective effects of on-line hemodiafiltration: comparison with
      conventional hemodialysis.
AB  - Atherosclerotic complications have a significant effect on mortality in patients
      undergoing hemodialysis (HD) therapy. However, anti-atherosclerotic and
      cardioprotective effects of on-line hemodiafiltration (HDF) remain to be
      elucidated. We prospectively compared the anti-atherosclerotic and
      cardioprotective effects in two randomly divided groups, i.e. on-line HDF group
      (n = 13) and conventional HD group (n = 9) for 1 year. Surrogate markers were
      brachial-ankle pulse wave velocity (baPWV), intima-media thickness (IMT) of
      carotid artery as an atherosclerosis marker, and cardiac functional surrogate
      markers included left ventricular mass index (LVMI), ejection fraction (EF), and
      LV diastolic capacity represented as E/A and deceleration time (DT). LVMI in on
      line HDF patients showed significant regression after 1 year of treatment (131.9
      +/- 25.8 to 116.5 +/- 24.7 g/m(2), P = 0.03), while LVMI in HD patients did not
      show any significant change (148.0 +/- 47.1 to 142.3 +/- 35.5 g/m(2)). Levels of
      baPWV in HD patients showed a significant increase (11.4%) from basal levels,
      while on-line HDF groups showed no significant increase. Furthermore, HD patients
      showed significant worsening of LV diastolic capacity (E/A: from 0.87 +/- 0.12 to
      0.79 +/- 0.08, P = 0.03), while it was not shown in on-line HDF patients.
      Ejection fraction and IMT did not show any significant change in both groups.
      Serum albumin, C-reactive protein, beta2 microglobulin, blood pressure, and anti
      hypertensive drug use did not change in both groups. On-line HDF showed a
      significant improvement in LVMI and prevented a significant worsening of baPWV or
      LV diastolic capacity compared with patients on conventional HD therapy.

PMID- 22458400
TI  - Low density lipoprotein apheresis ameliorates interferon-gamma production in
      patients with nephrotic syndrome.
AB  - Rapid amelioration of hypercholesterolemia in nephrotic syndrome (NS) using low
      density lipoprotein-apheresis (LDL-A) sometimes leads to NS remission, along with
      improvement of impaired biodefense system; however, the mechanism of how LDL-A
      affects NS is still unknown. We studied IFN-gamma production under IL-12
      stimulation for 24 h in whole blood from 30 NS patients, 31 non-NS patients, 35
      healthy volunteers and another four persistent NS patients due to refractory
      focal segmental glomerulonephritis and minimal change type nephrotic syndrome. We
      compared IFN-gamma production in whole blood and peripheral blood mononuclear
      cells (PBMC) from persistent NS patients before and after each of 14 LDL-A
      procedures. Finally, we studied the effect that persistent NS patients' serum
      before and after LDL-A had on IFN-gamma production in healthy volunteers' PBMC.
      Whole blood IFN-gamma production was significantly lower in NS patients compared
      with healthy volunteers or non-NS patients. In persistent NS, after LDL-A, IFN
      gamma production returned to normal levels. IFN-gamma production in PBMC varied
      greatly among these patients and did not show consistent changes after LDL-A.
      Healthy volunteers PBMC incubated with persistent NS patients' serum obtained
      after LDLA showed higher IFN-gamma production than before LDL-A. IFN-gamma
      production in peripheral blood is impaired if a patient is in a nephrotic state.
      LDL-A might restore suppressed PBMC function in persistent NS patients, thereby
      ameliorating the nephrotic state, possibly through removing interfering serum
      factors.

PMID- 22458401
TI  - Continuous hemodiafiltration for potential amniotic fluid embolism: dramatic
      responses observed during a 10-year period report of three cases.

PMID- 22458402
TI  - Peritoneal dialysis with Takayasu arteritis: a report of three cases.

PMID- 22458403
TI  - Retraction. An Australian experience with the Molecular Adsorbents Recirculating
      System (MARS).

PMID- 22458407
TI  - Lanthanide-based NMR: a tool to investigate component distribution in mixed
      monolayer-protected nanoparticles.
AB  - Gd(3+) ions, once bound to the monolayer of organic molecules coating the surface
      of gold nanoparticles, produce a paramagnetic relaxation enhancement (PRE) that
      broadens and eventually cancels the signals of the nuclear spins located nearby
      (within 1.6 nm distance). In the case of nanoparticles coated with mixed
      monolayers, the signals arising from the different coating molecules experience
      different PRE, depending on their distance from the binding site. As a
      consequence, observation of the signal broadening patterns provides direct
      information on the monolayer organization.

PMID- 22458406
TI  - Atypical antipsychotics--effects of amisulpride on salivary secretion and on
      clozapine-induced sialorrhea.
AB  - OBJECTIVE: Amisulpride is suggested for treatment of clozapine-induced
      sialorrhea. However, objective measurements of its effectiveness are lacking and,
      preclinically, amisulpride has no effect. We currently hypothesise that
      amisulpride acts by reducing the nervous- rather than the clozapine-driven
      salivary secretion. MATERIAL AND METHODS: Effects of intravenous amisulpride (as
      well as of clozapine and raclopride, a dopamine D2/D3 antagonist) were
      investigated in rats, including those subjected to chronic preganglionic
      parasympathetic denervation (submandibular glands) or combined postganglionic
      parasympathetic and sympathetic denervation (parotid glands). In duct-cannulated
      glands, secretion was evoked reflexly, at low and maximum flow rates, and by
      electrical stimulation of the parasympathetic and sympathetic innervations, and
      administration of autonomimetics (including substance P). RESULTS: Unlike
      clozapine, amisulpride had no effect on the reflexly evoked secretion at maximum
      rate. With respect to reflex secretion at low rate and to the secretion evoked by
      muscarinic, alpha-adrenergic, beta-adrenergic and substance P receptors,
      amisulpride (in contrast to raclopride) dose dependently potentiated the
      responses. Amisulpride had no effect on gland blood flow. CONCLUSIONS: No support
      for any inhibitory influence of amisulpride was found. Conversely, amisulpride
      universally enhanced secretion, suggesting that amisulpride is a potential drug
      for dry-mouth treatment. The mechanism behind the potentiation is currently
      unknown.

PMID- 22458408
TI  - Novel 3D hierarchical cotton-candy-like CuO: surfactant-free solvothermal
      synthesis and application in As(III) removal.
AB  - Novel three-dimensional (3D) hierarchical cotton-candy-like CuO microspheres were
      synthesized by a facile precursor templated conversion method. The precursor was
      prepared by solvothermal method in ethylene glycol (EG) without the use of any
      surfactant. The possible formation mechanism of the precursor was proposed and it
      was found that the synthetic parameters for the precursor such as the ratio of
      Cu(2+) to urea, the reaction temperature, and the use of EG are crucial for the
      formation of the cotton-candy-like CuO precursor nanostructures. The cotton-candy
      like CuO obtained by calcination were used as an adsorbent for removing As(III)
      in water. The adsorption isotherm, adsorption kinetics, the effects of competing
      anions and pH, and the adsorption mechanism were also investigated.

PMID- 22458409
TI  - Opposing actions of ethanol and nicotine on microRNAs are mediated by nicotinic
      acetylcholine receptors in fetal cerebral cortical-derived neural progenitor
      cells.
AB  - BACKGROUND: Ethanol (EtOH) and nicotine are often co-abused. However, their
      combined effects on fetal neural development, particularly on fetal neural stem
      cells (NSCs), which generate most neurons of the adult brain during the second
      trimester of pregnancy, are poorly understood. We previously showed that EtOH
      influenced NSC maturation in part, by suppressing the expression of specific
      microRNAs (miRNAs). Here, we tested in fetal NSCs the extent to which EtOH and
      nicotine coregulated known EtOH-sensitive (miR-9, miR-21, miR-153, and miR-335),
      a nicotine-sensitive miRNA (miR-140-3p), and mRNAs for nicotinic acetylcholine
      receptor (nAChR) subunits. Additionally, we tested the extent to which these
      effects were nAChR dependent. METHODS: Gestational day 12.5 mouse fetal murine
      cerebral cortical-derived neurosphere cultures were exposed to EtOH, nicotine,
      and mecamylamine, a noncompetitive nAChR antagonist, individually or in
      combination, for short (24 hour) and long (5 day) periods, to mimic exposure
      during the in vivo period of neurogenesis. Levels of miRNAs, miRNA-regulated
      transcripts, and nAChR subunit mRNAs were assessed by quantitative reverse
      transcription polymerase chain reaction. RESULTS: EtOH suppressed the expression
      of known EtOH-sensitive miRNAs and miR-140-3p, while nicotine at concentrations
      attained by cigarette smokers induced a dose-related increase in these miRNAs.
      Nicotine's effect was blocked by EtOH and by mecamylamine. Finally, EtOH
      decreased the expression of nAChR subunit mRNAs and, like mecamylamine, prevented
      the nicotine-associated increase in alpha4 and beta2 nAChR transcripts.
      CONCLUSIONS: EtOH and nicotine exert mutually antagonistic, nAChR-mediated
      effects on teratogen-sensitive miRNAs in fetal NSCs. These data suggest that
      concurrent exposure to EtOH and nicotine disrupts miRNA regulatory networks that
      are important for NSC maturation.

PMID- 22458410
TI  - Knowledge of HIV status prior to a community HIV counseling and testing
      intervention in a rural district of south Africa: results of a community based
      survey.
AB  - BACKGROUND: The low uptake of facility-based HIV counseling and testing (HCT) in
      South Africa, particularly amongst men and youth has hindered attempts to
      increase access to effective treatment and prevention strategies. Many barriers
      to HIV testing have been described including long waiting times, transport to
      reach facilities, fear of lack of confidentiality and health systems factors such
      as stock outs of HIV test kits. The aim of this study was to undertake a
      community survey to determine rates of HCT in a rural area in order to plan a
      community intervention. METHODS: A community-based survey was undertaken in 16
      communities in Sisonke district, KwaZulu-Natal between September and November
      2008. A total of 5821 individuals participated in the survey of which 66% were
      females. Gender specific mixed effects logistic regression models were used to
      describe differences in socio-economic characteristics, and their association
      with HIV testing histories. RESULTS: Overall 1833 (32%) individuals in this rural
      area knew their HIV status. Prior testing was higher amongst women (39%) than
      amongst men (17%). Older men (> 24 years) were more likely to report having
      tested for HIV previously, with the highest likelihood (adjusted OR = 4.02; 95%
      CI: 2.71-5.99) among men in age group, 35-49 years. For women, age group 25-34
      years had the highest likelihood of having been previously tested (adjusted OR =
      1.30; 95% CI: 1.05-1.66). Being currently pregnant (adjusted OR 3.31; 95% CI:
      2.29-4.78) or having a child under five (adjusted OR 7.00; 95% CI: 5.84-8.39)
      were also associated with prior HIV testing amongst women. CONCLUSIONS: Overall,
      knowledge of HIV status in this rural sub-district is low. The relatively higher
      uptake of HIV testing among women is encouraging as it shows that PMTCT services
      are well functioning. However, these data suggest that there is an urgent need
      for scaling up HIV testing services in rural communities specifically targeting
      men and youth.

PMID- 22458411
TI  - Alcohol limits in older people.

PMID- 22458413
TI  - Palladium-catalyzed C-N cross coupling of sulfinamides and aryl halides.
AB  - The palladium-catalyzed C-N cross coupling of sulfinamides and aryl halides is
      reported. In the presence of Pd(2)(dba)(3), tBuXPhos, NaOH, and a small amount of
      water, the C-N cross coupling of chiral tert-butanesulfinamide and aryl halides
      was accomplished to give N-aryl tert-butanesulfinamide without racemization, and
      the coupling of racemic p-toluenesulfinamide smoothly afforded N-aryl p
      toluenesulfinamides. 2-Bromopyridine was also suitable for the coupling. Addition
      of a small amount of water to the catalytic system was of importance to obtain
      high yields.

PMID- 22458412
TI  - Screening and functional analysis of differentially expressed genes in EBV
      transformed lymphoblasts.
AB  - BACKGROUND: Epstain-Barr virus (EBV) can transform human B lymphocytes making
      them immortalized and inducing tumorigenic ability in vitro, but the molecular
      mechanisms remain unclear. The aim of the present study is to detect and analyze
      differentially expressed genes in two types of host cells, normal human
      lymphocytes and coupled EBV-transformed lymphoblasts in vitro using gene chips,
      and to screen the key regulatory genes of lymphocyte transformation induced by EB
      virus. METHODS: Fresh peripheral blood samples from seven healthy donors were
      collected. EBV was used to transform lymphocytes in vitro. Total RNA was
      extracted from 7 cases of the normal lymphocytes and transformed lymphoblasts
      respectively, marked with dihydroxyfluorane after reverse transcription, then
      hybridized with 4 * 44 K Agilent human whole genome microarray. LIMMA, String,
      Cytoscape and other softwares were used to screen and analyze differentially
      expressed genes. Real-time PCR was applied to verify the result of gene
      expression microarrays. RESULTS: There were 1745 differentially expressed genes
      that had been screened, including 917 up-regulated genes and 828 down-regulated
      genes. According to the results of Generank, String and Cytoscape analyses, 38
      genes may be key controlled genes related to EBV-transformed lymphocytes,
      including 22 up-regulated genes(PLK1, E2F1, AURKB, CDK2, PLCG2, CD80, PIK3R3,
      CDC20, CDC6, AURKA, CENPA, BUB1B, NUP37, MAD2L1, BIRC5, CDC25A, CCNB1, RPA3,
      HJURP, KIF2C, CDK1, CDCA8) and 16 down-regulated genes(FYN, CD3D, CD4, CD3G,
      ZAP70, FOS, HCK, CD247, PRKCQ, ITK, LCP2, CXCL1, CD8A, ITGB5, VAV3, CXCR4), which
      primarily control biological processes such as cell cycle, mitosis, cytokine
      cytokine pathway, immunity response and so on. CONCLUSIONS: Human lymphocyte
      transformation induced by EB virus is a complicated process, involving multiple
      genes and -pathways in virus-host interactions. Global gene expression profile
      analysis showed that EBV may transform human B lymphocytes by promoting cell
      cycle and mitosis, inhibiting cell apoptosis, hindering host immune function and
      secretion of cytokines.

PMID- 22458414
TI  - Allopregnanolone protects against dopamine-induced striatal damage after in vitro
      ischaemia via interaction at GABA A receptors.
AB  - Sex steroid hormones, such as progesterone, have been shown to display
      neuroprotective properties after various models of central nervous system injury,
      including cerebral ischaemia, although the mechanism(s) of action remain largely
      undetermined. Allopregnanolone, an active progesterone metabolite, may explain
      some of the protective actions of progesterone. We utilised an in vitro model of
      ischaemia to evaluate the neuroprotective potential of allopregnanolone and
      examine its interaction at the GABA(A)  receptor, which is hypothesised to be its
      main neuroprotective mechanism. In adult male mouse coronal caudate slices
      exposed to oxygen glucose deprivation (OGD), we measured aspects of OGD-induced
      dopamine release, which is neurotoxic during ischaemia, using fast cyclic
      voltammetry and also assessed tissue viability. The GABA(A)  agonist, muscimol,
      displayed a neuroprotective profile in terms of delaying the OGD-evoked dopamine
      efflux (P < 0.05) and reducing the amount of dopamine released after OGD (P <
      0.05). Allopregnanolone, at a concentration of 10(-6)  m, also displayed a
      neuroprotective profile because it significantly reduced the amount of dopamine
      efflux (P < 0.05) and reduced the loss of viable tissue after OGD compared to
      slices exposed to vehicle during OGD (P < 0.05). However, the effect of 10(-6)  m
      allopregnanolone on dopamine efflux was prevented in the presence of bicuculline,
      a competitive GABA(A)  receptor antagonist. These results describe the use of an
      in vitro model of ischaemia with respect to determining that allopregnanolone is
      neuroprotective during the acute phase of ischaemia, and also demonstrate that
      such actions are dependent, at least in part, upon interaction at the GABA(A) 
      receptor.

PMID- 22458415
TI  - Socioeconomic conditions and number of pain sites in women.
AB  - BACKGROUND: Women in deprived socioeconomic situations run a high pain risk.
      Although number of pain sites (NPS) is considered highly relevant in pain
      assessment, little is known regarding the relationship between socioeconomic
      conditions and NPS. METHODS: The study population comprised 653 women; 160
      recurrence-free long-term gynecological cancer survivors, and 493 women selected
      at random from the general population. Demographic characteristics and co
      morbidity over the past 12 months were assessed. Socioeconomic conditions were
      measured by Socioeconomic Condition Index (SCI), comprising education, employment
      status, income, ability to pay bills, self-perceived health, and satisfaction
      with number of close friends. Main outcome measure NPS was recorded using a body
      outline diagram indicating where the respondents had experienced pain during the
      past week. Chi-square test and forward stepwise logistic regression were applied.
      RESULTS AND CONCLUSION: There were only minor differences in SCI scores between
      women with 0, 1-2 or 3 NPS. Four or more NPS was associated with younger age,
      higher BMI and low SCI. After adjustment for age, BMI and co-morbidity, we found
      a strong association between low SCI scores and four or more NPS, indicating that
      there is a threshold in the NPS count for when socioeconomic determinants are
      associated to NPS in women.

PMID- 22458416
TI  - Measurement of educational attainment in school-aged children born preterm.

PMID- 22458417
TI  - Appreciating age diversity and German nurse well-being and commitment: co-worker
      trust as the mediator.
AB  - Nursing practice faces the challenges of succeeding with a great diversity of
      customers and managing a diverse workforce with a wide range of age differences.
      While age diversity can lead to increased creativity and a greater richness of
      values and skills, it can also lead to value clashes, disrespect of each other's
      viewpoints, and increased conflict. As a result, nurses frequently experience
      stress, work-life imbalance, and a withdrawal from commitment. We propose the
      injection of positive diversity mindsets (age diversity appreciation) as one
      remedy. Specifically, we suggest that age diversity appreciation is positively
      related to nurses' well-being (stress and work-life balance), and also positively
      related to their team commitment. We further hypothesize that nurses' trust in co
      workers mediates the hypothesized relationships. Our survey data of 138 nurses in
      a large hospital in Germany supported our hypotheses. We discuss both theoretical
      and managerial implications of our findings in the context of age diversity and
      nursing work outcomes in hospitals.

PMID- 22458418
TI  - Current perspectives on the volatile-producing fungal endophytes.
AB  - Microbial-derived volatiles are ubiquitous in the environment and actively
      engaged in bio-communication with other organisms. Recently, some volatile
      producing endophytes (VPEs), cryptic fungal symbionts persisting in healthy plant
      tissues, have attracted great attention due to their strong antibiotic activity
      or production of carbon chains that are identical to many of those found in
      petroleum, while other fragrant volatiles can be used in the flavoring
      industries. From an application-oriented and biotechnological point of view,
      these findings show significant promise for sustainable development of
      agriculture, forestry, and industry, especially in the control of fruit
      postharvest diseases, soil-borne pathogen management, and bio-fuel production. In
      comparison, the ecological importance of VPEs has only rarely been addressed and
      warrants further exploration. In this review, we summarize the current knowledge
      and future directions in this fascinating research field, and also highlight the
      constraints and progresses towards commercialization of VPEs products.

PMID- 22458419
TI  - The relationship between pain, disability, quality of life and cognitive
      behavioural factors in chronic back pain.
AB  - PURPOSE: This pilot study systematically examined the correlations between the
      outcome variables pain intensity, disability and health-related quality of life
      (HRQOL) and between these outcomes and known psychological risk factors for
      chronic low back pain (CLBP), such as depression, trait anxiety, avoidance- and
      endurance-related pain responses at two different assessment points. METHOD: Data
      from 52 CLBP inpatients treated in an orthopedic clinic were investigated at two
      points in time: during the first days after admission and 6 months after the
      termination of the inpatient treatment. Bivariate relationships between pain
      intensity, disability, HRQOL and psychological variables were examined with the
      help of Pearson product moment correlations. Furthermore, the differences that
      exist between correlations at baseline and follow-up were tested for
      significance. RESULTS: Significant and large differences were found between the
      correlations with low correlations at baseline and high correlations at the
      follow-up. Furthermore, HRQOL showed a positive correlation with endurance
      related and a negative correlation with avoidance-related pain responses.
      CONCLUSIONS: Focusing on a systematic comparison of two significant assessment
      time points in CLBP with an acute exacerbation at baseline, the results of this
      study underlined the recurrent course of LBP. The results highlight that the
      assessment time points play an important role in CLBP. IMPLICATIONS FOR
      REHABILITATION: * Low back pain is a major public health problem with high direct
      and indirect back-pain-related costs. * Chronic low back pain is a disabling
      disease which restricts quality of life. * Psychological factors may have a
      larger impact on disability and quality of life than pain itself. * The recurrent
      course of low back pain highlights the importance of multidisciplinary pain
      management even during acute exacerbations of pain.

PMID- 22458420
TI  - Patient-specific analysis of  FLT3 internal tandem duplications for the
      prognostication and monitoring of acute myeloid leukemia.
AB  - OBJECTIVES: Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3
      ( FLT3) gene occur in 13-35% of patients with acute myeloid leukemia (AML). FLT3
      ITD is associated with poor clinical outcome and is an indication for allogeneic
      stem cell transplantation (allo-SCT). METHODS: To investigate FLT3-ITD length,
      position, and mutational load in AML cases, we developed patient-specific
      quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR)
      assays and correlated the results with established sensitive minimal residual
      disease (MRD) parameters and clinical outcome. RESULTS: In 409 patients with AML,
      FLT3-ITDs could be detected in 54 cases (13%). Within our cohort, patients with
      FLT3-ITD >= 45 base pairs had significantly higher relapse rates (P = 0.03) and a
      worse overall survival (P = 0.03). Our method could be applied to 97% of FLT3-ITD
      positive patients and was as sensitive as other MRD parameters such as PML-RARA ,
      NPM1 mutations, or MLL -PTD (correlation: r = 0.63; 0.99, and 0.99,
      respectively). MRD negativity predicted lasting remission independent of allo-SCT
      (N = 7) or non-allo-SCT (N = 9). All paired diagnostic/relapsed samples showed
      FLT3-ITD positivity. Compared with bone marrow samples, FLT3-ITD analyses
      appeared to be equivalently sensitive in peripheral blood. CONCLUSIONS: We
      conclude that individualized monitoring of FLT3-ITD in patients with AML may
      guide treatment decisions and should be evaluated for the indication for allo
      SCT.

PMID- 22458422
TI  - Various colour gradations as a dermatoscopic feature of cutaneous angiosarcoma of
      the scalp.

PMID- 22458425
TI  - Arts-based research and knowledge translation: some key concerns for health-care
      professionals.

PMID- 22458423
TI  - Enhanced midbrain response at 6-month follow-up in cocaine addiction, association
      with reduced drug-related choice.
AB  - Drug addiction is characterized by dysregulated dopamine neurotransmission.
      Although dopamine functioning appears to partially recover with abstinence, the
      specific regions that recover and potential impact on drug seeking remain to be
      determined. Here we used functional magnetic resonance imaging (fMRI) to study an
      ecologically valid sample of 15 treatment-seeking cocaine addicted individuals at
      baseline and 6-month follow-up. At both study sessions, we collected fMRI scans
      during performance of a drug Stroop task, clinical self-report measures of
      addiction severity and behavioral measures of cocaine seeking (simulated cocaine
      choice); actual drug use in between the two study sessions was also monitored. At
      6-month follow-up (compared with baseline), we predicted functional enhancement
      of dopaminergically innervated brain regions, relevant to the behavioral
      responsiveness toward salient stimuli. Consistent with predictions, whole-brain
      analyses revealed responses in the midbrain (encompassing the ventral tegmental
      area/substantia nigra complex) and thalamus (encompassing the mediodorsal
      nucleus) that were higher (and more positively correlated) at follow-up than
      baseline. Increased midbrain activity from baseline to follow-up correlated with
      reduced simulated cocaine choice, indicating that heightened midbrain activations
      in this context may be marking lower approach motivation for cocaine.
      Normalization of midbrain function at follow-up was also suggested by exploratory
      comparisons with active cocaine users and healthy controls (who were assessed
      only at baseline). Enhanced self-control at follow-up was suggested by a trend
      for the commonly hypoactive dorsal anterior cingulate cortex to increase response
      during a drug-related context. Together, these results suggest that fMRI could be
      useful in sensitively tracking follow-up outcomes in drug addiction.

PMID- 22458424
TI  - Btc22  chaperone is required for secretion and stability of the type III secreted
      protein  Bsp22  in  Bordetella bronchiseptica.
AB  - The type III secretion system (T3SS) is a sophisticated protein secretion
      machinery that delivers bacterial virulence proteins into host cells. A needle
      tip protein, Bsp22 , is one of the secreted substrates of the T3SS and plays an
      essential role in the full function of the T3SS in Bordetella bronchiseptica. In
      this study, we found that BB1618 functions as a chaperone for Bsp22 . The
      deletion of BB1618 resulted in a dramatic impairment of Bsp22 secretion into the
      culture supernatants and Bsp22 stability in the bacterial cytosol. In contrast,
      the secretion of other type III secreted proteins was not affected by the BB1618
      mutation. Furthermore, the BB1618 mutant strain could not induce cytotoxicity and
      displayed the same phenotypes as the Bsp22 mutant strain. An immunoprecipitation
      assay demonstrated that BB1618 interacts with Bsp22 , but not with BopB and BopD
      . Thus, we identified BB1618 as a specific type III chaperone for Bsp22 .
      Therefore, we propose that BB1618 be renamed Btc22 for the Bordetella type III
      chaperone for Bsp22 .

PMID- 22458426
TI  - The first report of orthotopic liver transplantation in the Western world.
AB  - Until the present time, the first experimental liver transplant which led to the
      development of human liver transplantation is attributed to C. Stuart Welch who
      performed a heterotopic transplant in the canine species in 1955. In 1956, Jack
      Cannon is credited with the first animal orthotopic liver transplant although the
      species was not disclosed. This report is intended to set the historical record
      straight by acknowledging that Vittorio Staudacher in 1952 was the first to
      perform a liver transplant in a large animal model.

PMID- 22458427
TI  - Nosocomial acquisition of methicillin-resistant Staphyloccocus aureus (MRSA) and
      extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae in hospitalised
      patients: a prospective multicenter study.
AB  - BACKGROUND: The risk of acquisition of antibiotic resistant-bacteria during or
      shortly after antibiotic therapy is still unclear and it is often confounded by
      scarce data on antibiotic usage.Primary objective of the study is to compare
      rates of acquisition of methicillin-resistant Staphylococcus aureus and extended
      spectrum beta-lactamase-producing Enterobacteriaceae in hospitalised patients,
      after starting antibiotic therapy. METHODS/DESIGN: The study, running in three
      European hospitals, is a multicenter, prospective, longitudinal, observational
      cohort study funded from the European Community's Seventh Framework Programme
      [FP7/2007-2013] within the project 'Impact of Specific Antibiotic Therapies on
      the prevalence of hUman host ResistaNt bacteria' (acronym SATURN). Nasal and
      rectal screening for methicillin-resistant Staphylococcus aureus and extended
      spectrum beta-lactamase-producing Enterobacteriaceae will be obtained at hospital
      admission, discharge, at antibiotic start (t0, within one hour) and at the
      following intervals: day 3 (t1), 7 (t2), 15 (t3), and 30 (t4). Two nested case
      control studies will be performed. The objective of the first study will be to
      define individual level of risk related to specific antibiotics. Patients
      acquiring methicillin-resistant Staphylococcus aureus and extended spectrum beta
      lactamase-producing Enterobacteriaceae (cases) will be compared with patients not
      acquiring antibiotic-resistant strains after starting antibiotic therapy
      (controls; ratio 1:4). To define the impact of antibiotics on new acquisition of
      target antibiotic-resistant bacteria, a second nested case-control study will be
      done (ratio 1:4). Control group will be selected among patients not receiving
      antibiotics, admitted in the same ward on the day of the corresponding case, with
      negative cultures at admission. Epidemiological, clinical and microbiological
      data will be prospective collected. DISCUSSION: The rationale of this study is to
      better understand the impact of antibiotic use on acquisition, selection and
      transmission of antimicrobial resistant-bacteria in European hospitals. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01208519.

PMID- 22458428
TI  - The drunken self: the five-factor model as an organizational framework for
      characterizing perceptions of one's own drunkenness.
AB  - BACKGROUND: Existing literature supports the use of the five-factor model (FFM)
      personality dimensions (i.e., Neuroticism, Extraversion, Agreeableness,
      Intellect, and Conscientiousness) as a comprehensive representation of mood,
      affect, and behavior. This study evaluated the use of the FFM as an
      organizational framework for understanding self-reported perceptions of
      drunkenness (i.e., mood, affect, and behavior associated with alcohol
      intoxication). METHODS: Cross-sectional data were obtained through an online
      survey of college student drinkers (N = 988; 50% male, 85% white, mean age =
      18.2) in an Introductory Psychology course at a large, mid-western university.
      Participants reported on their perceptions of their sober and drunk
      "personalities" by rating items from Goldberg's International Personality Item
      Pool. RESULTS: Confirmatory factor analysis showed that sober and drunk
      personality structures fit the data equally well. On average, differences between
      perceived drunken and sober personality were pervasive; each of the 5 factors
      differed as a function of drunk versus sober state with perceived drunken
      personality associated with (in order of effect size) less conscientiousness,
      less intellect, less agreeableness, more extraversion, and less neuroticism.
      These general patterns varied by sex and drinking pattern. CONCLUSIONS: Findings
      support the use of the FFM as a framework for organizing self-reported
      perceptions of global changes in "personality" that occur under intoxication.

PMID- 22458430
TI  - Microbial community analysis in biocathode microbial fuel cells packed with
      different materials.
AB  - Biocathode MFCs using microorganisms as catalysts have important advantages in
      lowering cost and improving sustainability. Electrode materials and microbial
      synergy determines biocathode MFCs performance. In this study, four materials,
      granular activated carbon (GAC), granular semicoke (GS), granular graphite (GG)
      and carbon felt cube (CFC) were used as packed cathodic materials. The microbial
      composition on each material and its correlation with the electricity generation
      performance of MFCs were investigated. Results showed that different biocathode
      materials had an important effect on the type of microbial species in biocathode
      MFCs. The microbes belonging to Bacteroidetes and Proteobacteria were the
      dominant phyla in the four materials packed biocathode MFCs. Comamonas of
      Betaproteobacteria might play significant roles in electron transfer process of
      GAC, GS and CFC packed biocathode MFCs, while in GG packed MFC Acidovorax may be
      correlated with power generation. The biocathode materials also had influence on
      the microbial diversity and evenness, but the differences in them were not
      positively related to the power production.

PMID- 22458429
TI  - Multiannual patterns of influenza A transmission in Chinese live bird market
      systems.
AB  - BACKGROUND: Avian influenza viruses (AIV) cause huge economic losses in poultry
      industries and pose a substantial threat to human health. However, predicting AIV
      epizootics and emergence in humans is confounded by insufficient empirical data
      on the ecology and dynamics of AIV in poultry systems. To address this gap, we
      quantified incidence patterns for 13 hemagglutinin subtypes of AIV using 6 years
      of surveillance data that were collected from ten different species of poultry
      and three different types of poultry holdings (contexts) - retail, wholesale, or
      farms. METHODS: We collected 42 646 samples in Shantou, China between 2000 and
      2006. We screened samples for hemagglutinin subtypes 1-13 of AIV and Avian
      Paramyxovirus-type-1 (APMV-1) using monospecific antisera in hemagglutination
      inhibition tests. We analyzed the data to determine seasonality patterns, subtype
      host, and subtype-subtype interactions as well as subtype bias in incidence in
      different contexts. RESULTS: H3, H6, H9, and APMV-1 were the most prevalent. No
      significant seasonality was found when all subtypes were considered together. For
      most AIV subtypes and APMV-1, there was subtype specificity for host, context,
      and coinfection partner. H5 showed the most generalized host usage pattern,
      followed by H9 and H6. CONCLUSION: Subtype-specific patterns because of host,
      context, and other subtypes suggest that risk assessments that exclude these
      details are likely inaccurate. Surveillance should include longitudinal sampling
      of multiple host species in multiple contexts. Quantitative models of control
      strategies must consider multiple subtypes, hosts, and source contexts to assess
      the effectiveness of interventions.

PMID- 22458431
TI  - Multifunctional protein-enabled patterning on arrayed ferroelectric materials.
AB  - This study demonstrates a biological route to programming well-defined protein
      inorganic interfaces with an arrayed geometry via modular peptide tag technology.
      To illustrate this concept, we designed a model multifunctional fusion protein,
      which simultaneously displays a maltose-binding protein (MBP), a green
      fluorescence protein (GFPuv) and an inorganic-binding peptide (AgBP2C). The fused
      combinatorially selected AgBP2C tag controls and site-directs the multifunctional
      fusion protein to immobilize on silver nanoparticle arrays that are fabricated on
      specific domain surfaces of ferroelectric LiNbO(3) via photochemical deposition
      and in situ synthesis. Our combined peptide-assisted biological and ferroelectric
      lithography approach offers modular design and versatility in tailoring surface
      reactivity for fabrication of nanoscale devices in environmentally benign
      conditions.

PMID- 22458432
TI  - "Largest amplitude ablation" is the optimal approach for typical atrial flutter
      ablation: a subanalysis from the AURUM 8 study.
AB  - INTRODUCTION: The recently proposed "maximum voltage-guided" (MVG) technique for
      radiofrequency catheter ablation of atrial flutter targets high-voltage
      electrograms along cavotricuspid isthmus (CTI) to ablate the functionally
      important anatomic muscle bundles alone, without drawing a complete anatomic line
      across the CTI. This innovative approach may shorten ablation time and procedure
      duration. METHODS AND RESULTS: Within the multicenter AURUM 8 study, which
      compared 8-mm gold- and Pt-Ir-tip catheters in atrial flutter ablation, we made a
      post hoc comparison of procedural data from 72 patients treated with MVG
      technique with data from 281 patients undergoing anatomic CTI ablation
      (unmatched) and with data from 72 patients selected from among those 281 patients
      such that they were matched with the MVG group with respect to selected baseline
      parameters and catheter type (matched). The MVG technique markedly reduced (P <
      0.001) ablation time (mean 6.9 minutes vs 10.9/9.7 minutes [unmatched/matched]),
      number of lesions (8.3 vs 13.7/12.9), fluoroscopy time (9.5 minutes vs 20.6/17.9
      minutes), procedure duration (59 minutes vs 93/86 minutes), and energy delivered
      (19 kJ vs 34/30 kJ) compared with anatomic CTI ablation. The incidence of
      charring was higher for MVG than for anatomic ablation technique (31.9% vs
      18.5/15.3%, P < 0.05), where Pt-Ir tip catheters were 6-fold more susceptible to
      charring than gold-tip catheters (P < 0.001), likely because of a lower thermal
      conductivity of the Pt-Ir material. The acute success rate was slightly better
      for MVG than for anatomic ablation technique (97.2% vs 92.2/91.7%, P = n.s.).
      CONCLUSION: Major procedural parameters are remarkably improved with MVG
      technique. Gold-tip catheters are substantially less susceptible to charring and
      may therefore be preferred over Pt-Ir-tip catheters for MVG ablation technique.

PMID- 22458433
TI  - High-precision tracking with non-blinking quantum dots resolves nanoscale
      vertical displacement.
AB  - Novel non-blinking quantum dots (NBQDs) were utilized in three-dimensional super
      localization, high-precision tracking applications under an automated scanning
      angle total internal reflection fluorescence microscope (SA-TIRFM). NBQDs were
      randomly attached to stationary microtubules along the radial axis under gliding
      assay conditions. By automatically scanning through a wide range of incident
      angles with different evanescent-field layer thicknesses, the fluorescence
      intensity decay curves were obtained. Fit with theoretical decay functions, the
      absolute vertical positions were determined with sub-10-nm localization
      precision. The emission intensity profile of the NBQDs attached to kinesin
      propelled microtubules was used to resolve the self-rotation of gliding
      microtubules within a small vertical distance of ~50 nm. We demonstrate the
      applicability of NBQDs in high-precision fluorescence imaging experiments.

PMID- 22458434
TI  - Suicide risk assessment practices: a national survey of generalist drug and
      alcohol residential rehabilitation services.
AB  - INTRODUCTION AND AIMS: Clients of drug and alcohol treatment services represent a
      high-risk group for attempted and completed suicide. The current study sought to
      examine suicide risk assessment practices in Australian generalist residential
      rehabilitation services. DESIGN AND METHODS: Semistructured interviews were
      conducted with managers of residential rehabilitation services and with
      volunteers from staff responsible for the case management/treatment of clients.
      RESULTS: Ninety per cent of services participated. In total, 64 managers and 142
      staff were interviewed. One-third of services had no documented policy for the
      assessment and management of suicide risk, and one-quarter of staff had never
      received formal training in risk assessment. In more than one-third of agencies
      staff were not expected to use a structured suicide risk assessment tool when
      assessing a client's acute risk. To varying degrees agencies were gathering
      information about psychiatric comorbidity, but this information did not appear to
      be routinely integrated into the client's suicide risk assessment. DISCUSSION AND
      CONCLUSIONS: The development of clearly documented polices, standardised
      assessment tools and the provision of annual training for all staff would help to
      address some of the gaps identified in current practice.

PMID- 22458436
TI  - Genetic effects of supportive stockings on native pikeperch populations in boreal
      lakes--cases, three different outcomes.
AB  - The genetic consequences and gene flow of pikeperch (Sander lucioperca) stocking
      were assessed in three boreal lakes based on admixture model analysis and
      comparison of the pre- and post-release patterns of genetic variability at 9 DNA
      microsatellite loci in the recipient populations. In two out of the three cases,
      the releases of fish from foreign populations caused significant changes in the
      genetic structure of the recipient population. The largest changes were observed
      in Lake Oulujarvi, where the post-release sample was almost identical to the
      released Lake Vanajanselka population, and about 90% of the catch was composed of
      the released population. The genetic composition of Lake Lohjanjarvi pikeperch
      also shifted markedly towards that of the released Lake Vanajanselka population,
      and about half of the later catch was of released Vanajanselka origin. In Lake
      Vanajanselka, in contrast, releases of pikeperch from lakes Painio and Averia had
      only a small impact on the genetic structure of the pikeperch population. These
      results indicate that the current stocking practices create an effective
      artificial gene flow that may strongly shape and reduce the genetic
      differentiation among the remaining native pikeperch populations. A common
      feature of all three cases was the lack of prior appraisal of the potential
      genetic and ecological risks in relation to the expected benefits of the release
      programmes.

PMID- 22458437
TI  - Identification of quantitative trait loci associated with small brown planthopper
      (Laodelphax striatellus Fallen) resistance in rice (Oryza sativa L.).
AB  - F(2) and BC(1) populations derived from the cross between 02428 / Rathu Heenati
      were used to investigate small brown planthopper (SBPH) resistance. Using the
      F(2) population, three QTLs for antixenosis against SBPH were located on
      chromosomes 2, 5 and 6, and accounted for 30.75% of the phenotypic variance;
      three QTLs for antibiosis against SBPH were detected on chromosomes 8, 9 and 12.
      qSBPH5-c explaining 7.21% of phenotypic variance for antibiosis was identified on
      chromosome 5 using the BC(1) population. A major QTL, qSBPH12-a1, explained about
      40% of the phenotypic variance, and a minor QTL, qSBPH4-a, was detected by the
      SSST method in both the F(2) and BC(1) populations. The QTLs indentified in the
      present study will be useful for marker assisted selection of SBPH resistance in
      rice.

PMID- 22458435
TI  - Regulation of reverse cholesterol transport - a comprehensive appraisal of
      available animal studies.
AB  - Plasma levels of high density lipoprotein (HDL) cholesterol are strongly
      inversely correlated to the risk of atherosclerotic cardiovascular disease. A
      major recognized functional property of HDL particles is to elicit cholesterol
      efflux and consequently mediate reverse cholesterol transport (RCT). The recent
      introduction of a surrogate method aiming at determining specifically RCT from
      the macrophage compartment has facilitated research on the different components
      and pathways relevant for RCT. The current review provides a comprehensive
      overview of studies carried out on macrophage-specific RCT including a quick
      reference guide of available data. Knowledge and insights gained on the
      regulation of the RCT pathway are summarized. A discussion of methodological
      issues as well as of the respective relevance of specific pathways for RCT is
      also included.

PMID- 22458438
TI  - Sympatric occurrence of four cytotypes and one extra chromosome in Bryconamericus
      ecai (Characidae): 18S rDNA polymorphism and heterochromatin composition.
AB  - In the present study, specimens of Bryconamericus ecai collected from the
      Forquetinha River/RS, were cytogenetically analyzed, disclosing a wide karyotypic
      diversity in this species. All individuals had 2n = 50, with different karyotypic
      formulae, resulting in four cytotypes and one B macrochromosome observed in
      cytotype III. Heterochromatin was distributed in the pericentromeric region of
      most chromosomes on the four cytotypes and also on a chromosome pair with
      interstitial markings in cytotype IV. Staining with CMA(3) and DAPI fluorochromes
      revealed a C-band region rich in AT base pairs in cytotypes I, II and III, and a
      pair with GC-rich heterochromatin in cytotypes II and III. Cytotype IV presented
      CMA(3) and DAPI positive heterochromatin. Silver nitrate impregnation, in situ
      hybridization, and fluorochrome staining showed a multiple system of AgNORs, 18S
      rDNA and CMA(3) sites in cytotypes I, III and IV, with both inter-and
      intraindividual variability in the number and location of these sites. Cytotype
      II had only one pair of NORs coincident with the 18S rDNA and CMA(3) sites,
      indicating a simple system. The chromosomal polymorphism observed among the
      specimens of B. ecai added to the literature data show that chromosomal
      rearrangements, especially pericentric inversions, play an important role in the
      karyotypic evolution of this group of fish. It can also be implied that more than
      one species of Bryconamericus is probably occurring, living in sympatry in the
      Forquetinha River/RS.

PMID- 22458439
TI  - Cytogenetic analysis of two species in the Phyllomedusa hypochondrialis group
      (Anura, Hylidae).
AB  - The genus Phyllomedusa has been the target of regular taxonomic investigations.
      The species Phyllomedusa nordestina was recently separated from P.
      hypochondrialis. Morphological variations in the P. rohdei interpopulation have
      already been reported, suggesting the existence of more than one taxon under that
      name. In the present study, we have cytogenetically characterized two populations
      of P. nordestina and one of P. rohdei. Both species displayed 2n = 26 chromosomes
      with 12 metacentric, 12 submetacentric and 2 subtelocentric chromosomes. The C
      banding analyses revealed discrete differences in the quantity of centromeric
      heterochromatin between the two species. The nucleolus organizer region (NOR) was
      detected in pair 9 of both species, but is located in the pericentromeric region
      of the short arm in P. nordestina and in the long arm subtelomeric region of P.
      rohdei. Chromosomal data from this study indicate karyotypic homeology between
      the two groups of P. hypochondrialis species and suggest the existence of more
      than one taxon under the P. rohdei name.

PMID- 22458440
TI  - Molecular characterization of HMW-GS 1Dx3(t) and 1Dx4(t) genes from Aegilops
      tauschii and their potential value for wheat quality improvement.
AB  - Two x-type high molecular weight glutenin subunits (HMW-GS) in Aegilops tauschii,
      1Dx3(t) and 1Dx4(t) were identified by SDS-PAGE and MALDI-TOF-MS. Their complete
      coding sequences were isolated by AS-PCR. 1Dx3(t) and 1Dx4(t) genes consist of
      2535 bp and 2508 bp and encode 845 and 836 amino acid residues, respectively. The
      deduced molecular masses of 1Dx3(t) and 1Dx4(t) gene products are 87655.26 Da and
      86664.24 Da, respectively, well corresponding to the molecular masses measured by
      MALDI-TOF-MS. A total of 18 SNPs were identified between 1Dx3(t) and 1Dx4(t).
      Comparing with 1Dx5 subunit, 1Dx3(t) had a six amino acid insertion at 146-151
      while the 1Dx4(t) had a nine amino acid deletion when compared with 1Dx3(t)
      subunit. The authenticity of the cloned 1Dx3(t) and 1Dx4(t) genes were confirmed
      by successful expression of their ORFs in E. coli. Comparison and phylogenetic
      tree based on the amino acid and nucleotide sequences confirmed that 1Dx3(t) was
      most closely related to 1Dx5 subunit that is widely accepted as a superior
      subunit for bread-making property. The secondary structure prediction
      demonstrated that 1Dx3(t) subunit has significantly high alpha-helix and beta
      strand contents, suggesting it might have positive effects on dough quality.

PMID- 22458441
TI  - Occurrence of pre-nucleolar bodies and 45S rDNA location on the chromosomes of
      the ant Mycocepurus goeldii (Forel) (Formicidae, Myrmicinae, Attini).
AB  - The ant Mycocepurus goeldii (Forel) is known for having a relict karyotype with
      low chromosome number and the present study help the understanding of this ant
      cytogenetics by describing the occurrence of pre-nucleolar bodies in their
      chromosomes using impregnation with silver nitrate (Ag-NOR) and the location of
      45S rDNA sites by means of the FISH (fluorescent in situ hybridization)
      technique. Several spots were observed surrounding all chromosomes when submitted
      to the Ag-NOR technique. These unusual markings were observed in both chromatids
      of metaphase and early anaphase chromosomes, and are associated to the presence
      of pre-nucleolar bodies, allowing the observation of the phenomenon of
      nucleologenesis. Although recent studies have shown that all chromosomes of M.
      goeldii exhibit centromeric or pericentromeric markings for the CMA(3)
      fluorochrome, the FISH technique indicated the presence of 45S rDNA in only one
      pair of chromosomes that differed in the number of CMA(3) markings observed for
      this species, pointing that the other markings observed with this fluorochrome do
      not match the sequences in ribosomal genes.

PMID- 22458443
TI  - Alzheimer's disease special thematic issue: call for papers.

PMID- 22458444
TI  - Rates of IUCD discontinuation and its associated factors among the clients of a
      social franchising network in Pakistan.
AB  - BACKGROUND: Modern Intrauterine contraceptive device (IUCD) is very safe, highly
      effective reversible and inexpensive family planning method which offers 5-10
      years of protection against pregnancy. The contraceptive use in Pakistan has been
      merely 30% for over a decade with IUCD being the least used method. Higher
      discontinuation rates are documented in developing countries; however no such
      data is available for Pakistan. Marie Stopes Society (MSS) established a social
      franchise outlets network branded as 'SURAJ' (Sun) in Pakistan to provide quality
      family planning services. This study attempts to determine IUCD discontinuation
      rates and its associated risk factors. Using a semi-structured questionnaire, a
      cross-sectional study was conducted with 3000 clients who availed IUCD services
      from Suraj provider 6, 12 and 24 month back,. Data were analyzed in SPSS 17.0;
      adjusted prevalence ratios were calculated to see associations between
      discontinuation and its risk factors. CASE PRESENTATION: We found that 22.7% of
      the IUCD acceptors experienced some health problem; while the overall
      discontinuation rate was 18.9% with average time of usage of 7.4 (SD +/- 5.8)
      months before discontinuation. Half of them showed health concerns (49.8%); of
      which a majority (70.2%) returned to Suraj provider for IUCD removal. Women
      living in Punjab, residing at a travelling time of 30-60 minutes and no previous
      use of contraceptive are more likely to discontinue IUCD. However, among total
      women 81.7% still expressed willingness to avail IUCD services from Suraj
      provider in future, if needed. CONCLUSION: The findings suggest a need for
      training the providers and field workers to prevent early discontinuation of IUCD
      among the Suraj clients and by addressing the health concerns through proper
      counseling, continued follow-up and immediate medical aid/referral in case of
      complications.

PMID- 22458445
TI  - Identification of reciprocal adhesion genes in pathogenic and non-pathogenic
      Pseudomonas.
AB  - We used a combination of in silico and large-scale mutagenesis approaches to
      expand our current knowledge of the genetic determinants used by Pseudomonas
      putida KT2440 to attach to surfaces. We first identified in silico orthologues
      that have been annotated in Pseudomonas aeruginosa as potentially involved in
      attachment. In this search 67 paired-related genes of P. putida KT2440 and P.
      aeruginosa were identified as associated to adhesion. To test the potential role
      of the corresponding gene products in adhesion, 37 knockout mutants of KT2440,
      available in the Pseudomonas Reference Culture Collection, were analysed with
      regard to their ability to form biofilms in polystyrene microtitre plates; of
      these, six mutants were deficient in adhesion. Since mutants in all potential
      adhesion genes were not available, we generated a genome-wide collection of
      mutants made of 7684 independent mini-Tn5 insertions and tested them for the
      formation of biofilm on polystyrene microtitre plates. Eighteen clones that
      exhibited a reduction of at least twofold in biofilm biomass formation were
      considered candidate mutants in adhesion determinants. DNA sequencing of the
      insertion site identified five other new genes involved in adhesion. Phenotypic
      characterization of the mutants showed that 11 of the inactivated proteins were
      required for attachment to biotic surfaces too. This combined approach allowed us
      to identify new proteins with a role in P. putida adhesion, including the global
      regulator RpoN and GacS, PstS that corresponds to one of the paired-related genes
      for which a mutant was not available in the mutant collection, and a protein of
      unknown function (PP1633). The remaining mutants corresponded to functions known
      or predicted to participate in adhesion based on previous evidence, such as the
      large adhesion proteins LapA, LapF and flagellar proteins. In silico analysis
      showed this set of genes to be well conserved in all sequenced P. putida strains,
      and that at least eight reciprocal genes involved in attachment are shared by P.
      putida and P. aeruginosa.

PMID- 22458446
TI  - MU-O bridged Mn10 assemblies with open O6 sites for binding extra guests:
      structural, magnetic, and surface studies.
AB  - High nuclearity [Mn(10)M(2)] clusters have been achieved through a self-assembly
      approach where multiple coordinating functional groups are incorporated into one
      ligand. When the hydrazone group appended with an oxime function as a reactive
      intermediate is used, the attachment of a vanillin subunit creates a ligand (L4)
      with three coordinating groups, which in their own right lead to cluster
      assemblies. The trifunctional ligand L4 produces a series of self-assembled,
      mixed oxidation state (Mn(II)/Mn(III)) Mn(10)M(2) based clusters with an overall
      linear structure comprising two connected pentanuclear Mn(5) halves, which bind
      alkali metal cations (M = Li, Na, K, Rb, Cs) and H(3)O(+) in the vanillin (O(6))
      end pockets, created by the assembly of three ligands around each Mn(5) subunit.
      Antiferromagnetic exchange dominates the spin coupling in the Mn(10) complexes,
      and surface studies on highly oriented pyrolytic graphite (HOPG) clearly show the
      arrangement of metal ions (Mn, Cs) in the Mn(10)Cs(2) linear cluster assembly.

PMID- 22458447
TI  - Editorial: The need for an effective hangover cure.

PMID- 22458448
TI  - Synthesis of the HCV protease inhibitor Vaniprevir (MK-7009) using ring-closing
      metathesis strategy.
AB  - A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in
      nine linear steps and 55% overall yield. The key features of this synthesis
      include a cost-effective synthesis of the isoindoline subunit and efficient
      construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009)
      utilizing ring-closing metathesis technology. A high-performing ring-closing
      metathesis protocol has been achieved by simultaneous slow addition of the
      ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13
      M.

PMID- 22458449
TI  - Characterization of a spore-specific protein of the Bacillus cereus group.
AB  - Bc1245 is a monocistronic chromosomal gene of Bacillus cereus ATCC 14579 encoding
      a putative protein of 143 amino acids identified in this study to have a spore
      related function in B. cereus. Bc1245 is highly conserved in the genome of
      members of the B. cereus group, indicating an important function of the gene in
      this group of bacteria. Quantitative PCR revealed that bc1245 is transcribed late
      in sporulation (upon formation of phase-bright spores) and at the same time as
      the mother cell-specific transcription factor sigma(K) . The sigma(K)  regulon
      includes structural components of the spore (such as coat proteins), and it is
      therefore plausible that bc1245 might encode a structural outer spore protein.
      This was confirmed by detection of BC1245 in exosporium extracts from B. cereus
      by immunoblotting against BC1245 antiserum.

PMID- 22458450
TI  - Fibroblast adhesion and activation onto micro-machined titanium surfaces.
AB  - OBJECTIVES: Surface modifications performed at the neck of dental implants, in
      the manner of micro-grooved surfaces, can reduce fibrous tissue encapsulation and
      prevent bacterial colonization, thereby improving fibrointegration and the
      formation of a biological seal. However, the applied procedures are technically
      complex and/or time consuming methods. The aim of this study was to analyse the
      fibroblast behaviour on modified titanium surfaces obtained, applying a simple
      and low-cost method. MATERIAL AND METHODS: An array of titanium surfaces was
      obtained using a commercial computerized numerical control lathe, modifying the
      feed rate and the cutting depth. To elucidate the potential ability of the
      generated surfaces to activate connective tissue cells, a thorough gene (by real
      time - qPCR) and protein (by western blot or zymography) expression and cellular
      response characterization (cell morphology, cell adhesion and cell activation by
      secreting extracellular matrix (ECM) components and their enzyme regulators) was
      performed. RESULTS: Micro-grooved surfaces have statistically significant
      differences in the groove's width (approximately 10, 50 and 100 MUm) depending on
      the applied advancing fixed speed. Field emission scanning electron microscopy
      images showed that fibroblasts oriented along the generated grooves, but they
      were only entirely accommodated on the wider grooves (>=50 MUm). Micro-grooved
      surfaces exhibited an earlier cell attachment and activation, as seen by collagen
      Ialpha1 and fibronectin deposition and activation of ECM remodelling enzymes,
      compared with the other surfaces. However, fibroblasts could remain in an
      activated state on narrower surfaces (<50 MUm) at later stages. CONCLUSIONS: The
      use of micro-grooved surfaces could improve implant integration at the gingival
      site with respect to polished surfaces. Micro-grooved surfaces enhance early
      fibroblast adhesion and activation, which could be critical for the formation of
      a biological seal and finally promote tissue integration. Surfaces with wider
      grooves (>=50 MUm) seem to be more appropriate than surfaces with narrow grooves
      (<50 MUm), as fibroblasts could persist in an activated state on narrower grooved
      surfaces, increasing the probability of producing a fibrotic response.

PMID- 22458451
TI  - The fingerprint of chemosymbiosis: origin and preservation of isotopic
      biosignatures in the nonseep bivalve  Loripes lacteus compared with  Venerupis
      aurea.
AB  - Endosymbionts in marine bivalves leave characteristic biosignatures in their host
      organisms. Two nonseep bivalve species collected in Mediterranean lagoons,
      thiotrophic symbiotic Loripes lacteus and filter-feeding nonsymbiotic Venerupis
      aurea, were studied in detail with respect to generation and presence of such
      signatures in living animals, and the preservation of these signals in subfossil
      (late Pleistocene) sedimentary shells. Three key enzymes from sulfur oxidation
      (APS-reductase), CO(2) fixation (RubisCO) and assimilation of nitrogen [glutamine
      synthetase (GS)] were detected by immunofluorescence in the bacterial symbionts
      of Loripes. In Loripes, major activity was derived from GS of the symbionts
      whereas in Venerupis the host GS is active. In search of geologically stable
      biosignatures for thiotrophic chemosymbiosis that might be suitable to detect
      such associations in ancient bivalves, we analyzed the isotopic composition of
      shell lipids (delta(13)C) and the bulk organic matrix of the shell (delta(13)C ,
      delta(15)N , delta(34)S). In the thiotrophic Loripes, delta(13)C values were
      depleted compared with the filter-feeding Venerupis by as much as 8.50/00 for
      individual fatty acids, and 4.40/00 for bulk organic carbon. Likewise, bulk
      delta(15)N and delta(34)S values were more depleted in recent thiotrophic
      Loripes. Whereas delta (34)S values were found to be unstable over time, the
      combined delta(15)N and delta(13)C values in organic shell extracts revealed a
      specific signature for chemosymbiosis in recent and subfossil specimens.

PMID- 22458452
TI  - Modifier genetics in neuropsychiatric disease: challenges and opportunities.
AB  - A new study focuses attention on multigenic interactions influencing the risk of
      autism spectrum disorders.

PMID- 22458453
TI  - Butenolide inhibits marine fouling by altering the primary metabolism of three
      target organisms.
AB  - Butenolide is a very promising antifouling compound that inhibits ship hull
      fouling by a variety of marine organisms, but its antifouling mechanism was
      previously unknown. Here we report the first study of butenolide's molecular
      targets in three representative fouling organisms. In the barnacle Balanus
      (=Amphibalanus) amphitrite, butenolide bound to acetyl-CoA acetyltransferase 1
      (ACAT1), which is involved in ketone body metabolism. Both the substrate and the
      product of ACAT1 increased larval settlement under butenolide treatment,
      suggesting its functional involvement. In the bryozoan Bugula neritina,
      butenolide bound to very long chain acyl-CoA dehydrogenase (ACADVL), actin, and
      glutathione S-transferases (GSTs). ACADVL is the first enzyme in the very long
      chain fatty acid beta-oxidation pathway. The inhibition of this primary pathway
      for energy production in larvae by butenolide was supported by the finding that
      alternative energy sources (acetoacetate and pyruvate) increased larval
      attachment under butenolide treatment. In marine bacterium Vibrio sp. UST020129
      010, butenolide bound to succinyl-CoA synthetase beta subunit (SCSbeta) and
      inhibited bacterial growth. ACAT1, ACADVL, and SCSbeta are all involved in
      primary metabolism for energy production. These findings suggest that butenolide
      inhibits fouling by influencing the primary metabolism of target organisms.

PMID- 22458454
TI  - Does time matter? Exploring the relationship between interdependent teamwork and
      time allocation in Swedish interprofessional teams.
AB  - This paper explores the relationship between time allocation on formal and
      informal forms of contact within interprofessional teams and an interdependent
      collaboration. Data were collected by a questionnaire including items on work
      organization, team climate and time allocation that was responded to by 226
      professionals from 44 interprofessional teams. An additional sample of 139
      professionals from 18 teams responded to the same questionnaire except for the
      item on time allocation. The teams worked within occupational health care,
      psychiatry, rehabilitation and school health care. On average, team members spent
      about 22% of their available work time on internal meetings/consultations and
      they perceived their collaboration as fairly interdependent. No correlation was
      found between, on the one hand, time invested in meetings and informal
      consultations within the team and, on the other hand, degree of team
      interdependence. Instead, interdependence was predicted by team climate, followed
      by manager coordination and self-regulation. However, there may be a lower limit:
      all 44 teams allocated at least about 10% of their work time to internal meetings
      and consultations. The results suggest three ways to strengthen interprofessional
      team collaboration - development of team climate and communication and more
      opportunity for both manager coordination and self-regulation.

PMID- 22458456
TI  - The graying of America: challenges and controversies.

PMID- 22458457
TI  - Must we ration health care for the elderly?
AB  - Resistance to rationing health care to the elderly is enormous. This article lays
      out the need for rationing, based on projections of Medicare expenditure in the
      near future, and the judgment of policy experts that there will be no
      technological breakthrough that might lower costs. Various forms of rationing
      possibilities are discussed as well as cultural and political obstacles to needed
      reform. Some general principles for thinking about health care for the elderly
      are presented.

PMID- 22458458
TI  - Can health care rationing ever be rational?
AB  - Americans' appetite for life-prolonging therapies has led to unsustainable growth
      in health care costs. It is tempting to target older people for health care
      rationing based on their disproportionate use of health care resources and
      lifespan already lived, but aged-based rationing is unacceptable to many. Systems
      reforms can improve the efficiency of health care and may lessen pressure to
      ration services, but difficult choices still must be made to limit expensive,
      marginally beneficial interventions. In the absence of agreement on principles to
      govern health care resource allocation, a fair, open priority-setting process
      should be created to allow for reasonable disagreement on principles while being
      seen as legitimate by all stakeholders. At the patient-care level, careful
      discussions about the benefits and burdens of medical intervention and support
      for slow medicine - a gentle, family-centered care approach for frail elders -
      can do much to avoid harming these patients with aggressive yet unwanted medical
      care while reducing wasteful spending.

PMID- 22458455
TI  - White matter volume in alcohol use disorders: a meta-analysis.
AB  - Atrophy of brain white matter (WM) often is considered a signature injury of
      alcohol use disorders (AUDs). However, investigations into AUD-related changes in
      WM volume have yielded complex findings that are difficult to synthesize in a
      narrative review. The objective of this study was to obtain an averaged effect
      size (ES) for WM volume reduction associated with AUD diagnosis and to test
      potential moderators of ES. Study inclusion criteria were: (1) English language;
      (2) peer reviewed; (3) published before December 2011; (4) use of magnetic
      resonance imaging (MRI); (5) human participants; (6) inclusion of AUD group; (7)
      inclusion of non-AUD comparison group; and (8) reporting or testing of total or
      cerebral WM volume. Moderators included study design, MRI methodology and AUD
      characteristics. Nineteen studies with a total of 1302 participants (70% male)
      were included, and calculated ESs were confirmed by the corresponding author for
      12 studies. The magnitude of the averaged ES adjusted for small sample bias
      (Hedges' g) for WM reduction in AUDs was 0.304 (standard error = 0.134, range = 
      0.57-1.21). Hierarchical linear modeling indicated that the overall ES differed
      significantly from 0, t(18) = 2.257, P = 0.037, and that the distribution of the
      19 ESs showed significant heterogeneity beyond sampling error, chi(2) (18) =
      52.400, P < 0.001. Treatment-seeking status and length of abstinence were
      significant moderators of ES distribution. These results are suggestive of WM
      recovery with sustained abstinence and point to the need for further
      investigation of factors related to treatment-seeking status.

PMID- 22458459
TI  - Social justice, health disparities, and culture in the care of the elderly.
AB  - Older minority Americans experience worse health outcomes than their white
      counterparts, exhibiting the need for social justice in all areas of their health
      care. Justice, fairness, and equity are crucial to minimizing conditions that
      adversely affect the health of individuals and communities. In this paper,
      Alzheimer's disease (AD) is used as an example of a health care disparity among
      elderly Americans that requires social justice interventions. Cultural factors
      play a crucial role in AD screening, diagnosis, and access to care, and are often
      a barrier to support and equality for minority communities. The "conundrum of
      health disparities" refers to the interplay between disparity, social justice,
      and cultural interpretation, and encourages researchers to understand both (1)
      disparity caused by economic and structural barriers to access, treatment, and
      diagnosis, and (2) disparity due to cultural interpretation of disease, in order
      to effectively address health care issues and concerns among elderly Americans.

PMID- 22458460
TI  - Looking for better health in all the wrong places: the road to "equality" hits a
      dead end.
AB  - The actual evidence base for measures of health inequality among the elderly in
      the United States remains rather thin. Addressing the real causes of health
      inequalities will require measuring what matters, accounting for the time lags
      and non-health-care factors behind the development of future health conditions
      and outcomes, and setting better priorities and targets. An early intervention
      strategy should focus more on future generations of elderly Americans when they
      are young.

PMID- 22458461
TI  - Testing the medical covenant: caring for patients with advanced dementia.
AB  - End-of-life care, particularly for patients with advanced dementia, tests the
      medical covenant, both the integrity and aptness of what physicians have to offer
      and the fidelity with which they offer it. This article considers five ways of
      justifying the unilateral withholding of future treatment: (1) an affirmation of
      professional autonomy; (2) a defense of professional integrity; (3) a parentalist
      exercise of power on behalf of the patient and/or family; (4) a protection of the
      interests of third parties (footing the bill); or (5) a protection of the
      interests of second parties (the physician or other providers). The article
      concludes with a sixth response to care for the stricken patient and family that
      seeks to attend more fully to the clinical reality of bonded humans in the throes
      of disease and death.

PMID- 22458462
TI  - Doing the right thing: a geriatrician's perspective on medical care for the
      person with advanced dementia.
AB  - Developing a reasonable approach to the medical care of older people with
      dementia will be essential in the coming decades. Physicians are the locus of
      decision making for persons with dementia. It is the responsibility of the
      physician to assure that the surrogate understands the nature and trajectory of
      the disease and then to elicit the desired goal of care. Physicians need to
      ascertain whether any advance directives are available, and if so, whether they
      apply to the situation of advanced dementia. Finally, physicians should help
      surrogates understand how the goals of care are best translated into practice.
      When the goal is comfort, this is achieved by assuring dignity, minimizing
      suffering, and promoting caring. In general, comfort should be the default goal
      of care, best implemented through palliative care or hospice.

PMID- 22458463
TI  - Physicians should "assist in suicide" when it is appropriate.
AB  - Palliative care and hospice should be the standards of care for all terminally
      ill patients. The first place for clinicians to go when responding to a request
      for assisted death is to ensure the adequacy of palliative interventions.
      Although such interventions are generally effective, a small percentage of
      patients will suffer intolerably despite receiving state-of-the-art palliative
      care, and a few of these patients will request a physician-assisted death. Five
      potential "last resort" interventions are available under these circumstances:
      (1) accelerating opioids for pain or dyspnea; (2) stopping potentially life
      prolonging therapies; (3) voluntarily stopping eating and drinking; (4)
      palliative sedation (potentially to unconsciousness); and (5) physician-assisted
      death. Patient, family, and clinicians should search for the least harmful way to
      respond to intolerable end-of-life suffering in ways that are effective and also
      respect the values of the major participants. A system that allows an open
      response to such cases ultimately protects patients by ensuring a full clinical
      evaluation and search for alternative responses, while reinforcing the need to be
      responsive and to not abandon.

PMID- 22458464
TI  - Are the distinctions drawn in the debate about end-of-life decision making
      "principled"? If not, how much does it matter?
AB  - The current ethical-legal consensus - prohibiting assisted suicide and
      euthanasia, but (1) allowing patients to forgo all life-saving treatment, and (2)
      permitting pain relief that increases the risk of death - is a means of having it
      both ways. This is how we often make "tragic choices."

PMID- 22458465
TI  - Public health ethics theory: review and path to convergence.
AB  - Public health ethics is a nascent field, emerging over the past decade as an
      applied field merging concepts of clinical and research ethics. Because the
      "patient" in public health is the population rather than the individual, existing
      principles might be weighted differently, or there might be different ethical
      principles to consider. This paper reviewed the evolution of public health
      ethics, the use of bioethics as its model, and the proposed frameworks for public
      health ethics through 2010. Review of 13 major public health ethics frameworks
      published over the past 15 years yields a wide variety of theoretical approaches,
      some similar foundational values, and a few similar operating principles. Coming
      to a consensus on the reach, purpose, and ends of public health is necessary if
      we are to agree on what ethical underpinnings drive us, what foundational values
      bring us to these underpinnings, and what operating principles practitioners must
      implement to make ethical decisions. If public health is distinct enough from
      clinical medicine to warrant its own set of ethical and philosophical
      underpinnings, then a decision must be made as to whether a single approach is
      warranted or we can tolerate a variety of equal but different perspectives.

PMID- 22458466
TI  - Conflicts among multinational ethical and scientific standards for clinical
      trials of therapeutic interventions.
AB  - Utilizing a sorted compendium of international clinical trial standards,
      investigators identified 15 conflicts among ethical and methodological guidance.
      Analysis distinguishes interpretational issues, lack of clarity, and
      contradiction as factors to be addressed if international trial guidance is to be
      improved.

PMID- 22458467
TI  - The roles and responsibilities of physicians in patients' decisions about
      unproven stem cell therapies.
AB  - Capitalizing on the hype surrounding stem cell research, numerous clinics around
      the world offer "stem cell therapies" for a variety of medical conditions.
      Despite questions about the safety and efficacy of these interventions, anecdotal
      evidence suggests a relatively large number of patients are traveling to receive
      these unproven treatments - a practice called "stem cell tourism." Because these
      unproven treatments pose risks to individual patients and to legitimate
      translational stem cell research, stem cell tourism has generated substantial
      policy concern and inspired attempts to reduce these risks through the
      development of guidelines for patients and medical practitioners. This paper
      examines the roles and responsibilities of physicians in patients' home countries
      with respect to patients' decisions to try unproven stem cell therapies abroad.
      Specifically, it examines professional guidance from two organizations - the
      American Medical Association and the International Society for Stem Cell Research
      - and assesses physicians' professional and legal obligations to patients
      considering unproven stem cell therapies. Then, drawing on qualitative interviews
      conducted with patients who traveled abroad for unproven stem cell treatments, it
      explores the roles that physicians actually play in patients' decisions and
      compares these actual roles with their professional and legal responsibilities.
      The paper concludes with a discussion of strategies to help improve the guidance
      physicians provide to patients considering unproven treatments.

PMID- 22458468
TI  - The impact of defense expenses in medical malpractice claims.
AB  - The objective of this study was to take a closer look at defense-related expenses
      for medical malpractice cases over time. We conducted a retrospective review of
      medical malpractice claims reported to the Physician Insurers Association of
      America's Data Sharing Project with a closing date between January 1, 1985 and
      December 31, 2008. On average a medical malpractice claim costs more than $27,000
      to defend. Claims that go to trial are much more costly to defend than are those
      that are dropped, withdrawn, or dismissed. However, since the overwhelming
      majority of claims are dropped, withdrawn, or dismissed, the total amount spent
      to defend them surpasses that spent on claims that go to trial. Defense attorney
      expenses account for the majority of defense-related expenses (74%), while expert
      witness expenses and other expenses split the remaining 26%. A strong association
      was also found between the average indemnity payment and the amount it costs to
      defend individual claims by specialty. Our study found that defense-related
      expenses for medical malpractice claims are not an insignificant cost. As state
      and federal governments debate how to repair the malpractice system, addressing
      the high cost of defending claims should not be ignored.

PMID- 22458469
TI  - Currents in contemporary bioethics. Open access as benefit sharing? The example
      of publicly funded large-scale genomic databases.

PMID- 22458470
TI  - Teaching health law.

PMID- 22458472
TI  - Recent developments in health law. Accountability after Guantanamo: the role of
      U.S. health professionals.

PMID- 22458473
TI  - Respiratory tract versus cloacal sampling of migratory ducks for influenza A
      viruses: are both ends relevant?
AB  - BACKGROUND: Early studies in dabbling ducks showed that cloacal swabs yielded a
      larger number of avian influenza virus (AIV) isolates than did respiratory tract
      swabs. Historically, AIV surveillance has been performed by collecting cloacal or
      environmental fecal samples only. Highly pathogenic avian influenza H5N1 virus
      emerged in 1996 and replicated to higher titers in the respiratory rather than
      the gastrointestinal tract of ducks, prompting the collection of respiratory
      samples in addition to cloacal swabs from wild birds. Studies confirmed that some
      virus subtypes, especially H9 and highly pathogenic H5, are shed primarily
      through the respiratory tract and may not be detected in cloacal swabs.
      OBJECTIVES: To examine prevalence and subtype differences for AIV isolates from
      cloacal or respiratory swabs of wild ducks and to determine whether individual
      respiratory tract samples should be included in AIV surveillance studies in wild
      birds. METHODS: Individual respiratory tract and cloacal swabs were collected
      from each of 1036 wild ducks in Alberta, Canada, during the month of August from
      2007 to 2010 in an ongoing surveillance study. Virus isolation in eggs and
      subtype identification by antigenic and molecular methods were performed. RESULTS
      AND CONCLUSIONS: Respiratory tract and cloacal swabs yielded ten influenza virus
      HA subtypes representing 28 HA-NA combinations. Three HA-NA subtype combinations
      were found exclusively in respiratory tract samples. Only four HA subtypes (H1,
      H3, H4, and H7) were recovered from respiratory samples, but respiratory shedding
      was associated with the dominance of 1 year's subtype. Might respiratory shedding
      provide a risk assessment indicator?

PMID- 22458474
TI  - Macrophages participate in host protection and the disease pathology associated
      with Leishmania braziliensis infection.
AB  - BACKGROUND: Leishmania preferentially infects macrophages, which allow the
      parasite to multiply but can also kill the parasite. Although the T cell response
      in human leishmaniasis is well-characterized, little is known about the
      concomitant macrophage behavior. The aim of this study was to characterize the
      macrophage immune response after Leishmania braziliensis infection in cells
      derived from cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML) patients,
      subclinical individuals (SC) and healthy control subjects (HS). METHODS:
      Peripheral blood mononuclear cell-derived macrophages from the different groups
      were exposed to L. braziliensis in vitro and were evaluated for susceptibility to
      Leishmania infection, ability to kill Leishmania and chemokine/cytokine
      production. Nitric Oxide (NO) and superoxide (O2-) levels in the supernatant of
      infected macrophage cultures were monitored. RESULTS: After exposure to L.
      braziliensis, peripheral blood mononuclear cell-derived macrophages from SC
      individuals showed a lower infection rate and a smaller number of intracellular
      amastigotes compared to cells from CL and ML patients. Macrophages from CL and ML
      patients produced more chemokines and TNF-alpha than those from the SC group.
      Production of NO and O2- were detected but did not vary significantly among the
      different groups. CONCLUSIONS: Our data indicate that macrophages play a pivotal
      role in controlling L. braziliensis infection and in leishmaniasis pathology by
      secreting pro-inflammatory chemokines/cytokines that activate and recruit T
      cells, overwhelming the inflammatory response.

PMID- 22458475
TI  - Variation in metabolic responses to meal challenges differing in glycemic index
      in healthy women: Is it meaningful?
AB  - BACKGROUND: Established clinical tests are commonly used in disease diagnosis,
      but tools that enhance identification of metabolic dysfunctions are needed. This
      study was conducted to identify typical and atypical metabolite temporal patterns
      in response to paired meal challenge tests. DESIGN: Metabolic responses to high
      and low glycemic index (GI) meals were tested in 24 healthy pre-menopausal women,
      aged 20-50 y, with BMI of 25-30 kg/m2 using a cross-over design. On test days,
      blood glucose, insulin, leptin and non-esterified fatty acids were measured after
      an overnight fasting, and for 8 h following test meal consumption. The data were
      range scaled, and multivariate statistics were used to assess the presence of
      distinct response groups to the meal challenge tests. RESULTS: As expected,
      participants showed higher circulating glucose and insulin in response to the
      high GI compared to the low GI meal challenge. However, using range-scaling and
      Principal Component Analysis, three distinct groups were identified based on
      differential responses to the paired challenges. Members of the most populated
      group (n = 18) displayed little deviation from the expected response to the two
      meal challenges. Two minor groups (n = 3/group) with distinct responses were
      observed, one suggestive of sub-clinical insulin resistance, and the other
      suggestive of hyperleptinemia. CONCLUSIONS: The differential responses of
      glucose, insulin and leptin to low and high glycemic test meals revealed three
      response groups. Dietary intervention studies traditionally evaluate group
      responses, and aim to identify the overall effect in the population studied. In
      contrast, our study analyzed the variance in the meal challenge responses, using
      an integrated physiological approach, rather than a reductionist approach. This
      phenotyping approach may be useful for detecting subclinical metabolic
      dysfunctions, and it could contribute to improved personalized nutrition
      management. This study is registered in ClinicalTrials.gov, record #200210295.

PMID- 22458476
TI  - Chiral Ni(II) coordination polymers: structure-driven effects of temperature and
      polyvinylpyrrolidone.
AB  - Chiral Ni(II) coordination compounds with structures of [NiL(H(2)O)(3)] (1) and
      {[NiL(H(2)O)].0.5H(2)O}(n) (2) (H(2)L = thiazolidine 2,4-dicaboxlic acid) have
      been successfully synthesized by the reaction of Ni(CH(3)COO)(2).4H(2)O and H(2)L
      in aqueous solution at 25 and 80  degrees C, respectively. From the same
      procedure with polyvinylpyrrolidone (PVP) as a surfactant, another corresponding
      micrometer-scale Ni(II) coordination polymer, {[NiL(H(2)O)(2)].H(2)O}(n) (3), has
      been obtained at both 25 and 80  degrees C, which shows a different structure
      (one-dimensional, 1D) than both 1 (discrete molecule) and 2 (3D). The conversions
      of structures and conformations are directed by temperature and surfactant (PVP),
      as confirmed by powder and single-crystal X-ray diffraction. Circular Dichroism
      (CD) and Second Harmonic Generation (SHG) measurements of the products have been
      investigated as well, which indicate the potential applications of these products
      in chiral and nonlinear optical (NLO) areas.

PMID- 22458481
TI  - Recollections of Christchurch.

PMID- 22458477
TI  - Bacterial biosynthesis and maturation of the didemnin anti-cancer agents.
AB  - The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum
      solidum was the first marine drug to be clinically tested in humans. Because of
      its limited supply and its complex cyclic depsipeptide structure, considerable
      challenges were encountered during didemnin B's development that continue to
      limit aplidine (dehydrodidemnin B), which is currently being evaluated in
      numerous clinical trials. Herein we show that the didemnins are bacterial
      products produced by the marine alpha-proteobacteria Tistrella mobilis and
      Tistrella bauzanensis via a unique post-assembly line maturation process.
      Complete genome sequence analysis of the 6,513,401 bp T. mobilis strain KA081020
      065 with its five circular replicons revealed the putative didemnin biosynthetic
      gene cluster (did) on the 1,126,962 bp megaplasmid pTM3. The did locus encodes a
      13-module hybrid non-ribosomal peptide synthetase-polyketide synthase enzyme
      complex organized in a collinear arrangement for the synthesis of the fatty
      acylglutamine ester derivatives didemnins X and Y rather than didemnin B as first
      anticipated. Imaging mass spectrometry of T. mobilis bacterial colonies captured
      the time-dependent extracellular conversion of the didemnin X and Y precursors to
      didemnin B, in support of an unusual post-synthetase activation mechanism.
      Significantly, the discovery of the didemnin biosynthetic gene cluster may
      provide a long-term solution to the supply problem that presently hinders this
      group of marine natural products and pave the way for the genetic engineering of
      new didemnin congeners.

PMID- 22458482
TI  - Unexpected interludes as a President's wife!

PMID- 22458483
TI  - Anniversary of the Christchurch earthquake.

PMID- 22458484
TI  - Christchurch earthquake: a pre-training trainee's perspective.

PMID- 22458485
TI  - Christchurch rocks.

PMID- 22458486
TI  - The growth of a Society: a journey in the development of governance, management,
      and administration.
AB  - A review of the history and development of the Urological Society of Australasia
      now the Urological Society of Australia and New Zealand. What's known on the
      subject? and What does the study add? The history of The Urological Society of
      Australasia was written by Sally Wilde and published by Hyland House in
      1999.Whilst this documented geographical and numerical growth along with some
      structural changes, it did not discuss the change in and development of
      organisational structure. This paper describes how the growth of an organisation
      can at times proceed at a rate not matched by concurrent growth in organisational
      skill. The need for review of structure and the mechanism to affect change that
      matches and facilitates growth, together with some of the consequences are
      discussed.

PMID- 22458487
TI  - Acute management of priapism in men.
AB  - What's known on the subject? and What does the study add? Priapism is a rare
      event. However, various medications and medical conditions may increase the risk.
      Priapism can be ischaemic, non-ischaemic or stuttering. It is paramount to
      distinguish the type of priapism, as misdiagnosis may lead to significant
      morbidity. Ischaemic priapism represents a compartment syndrome of the penis and
      is therefore a medical emergency. A delay in management may significantly affect
      future erectile function. Stuttering priapism represents recurrent subacute
      episodes of ischaemic priapism, which may lead to erectile dysfunction. Thus
      episodes must be minimised. Non-ischaemic priapism is not a medical emergency.
      However, misdiagnosis and injection with sympathomimetic agents can result in
      system absorption and toxicity. This review article provides a summary of the
      evaluation and management of priapism. Furthermore, a step by step flow chart is
      provided to guide the clinician through the assessment and management of this
      complex issue. OBJECTIVES: To review the literature regarding ischaemic, non
      ischaemic and stuttering priapism. To provide management recommendations.
      PATIENTS AND METHODS: A Medline search was carried out to identify all relevant
      papers with management guidelines for priapism. RESULTS: Ischaemic priapism
      represents a compartment syndrome of the penis and urgent intervention is
      required to decrease the risk of erectile dysfunction. Non-ischaemic priapism is
      not a medical emergency; however, it can result in erectile dysfunction. The
      treatment objective for stuttering priapism is to reduce future episodes with
      systemic treatments, whilst treating each ischaemic episode as an emergency.
      CONCLUSIONS: Priapism is a complex condition that requires expert care to prevent
      complications and irreversible erectile dysfunction.

PMID- 22458488
TI  - In situ and intraductal epithelial proliferations of prostate: definitions and
      treatment implications. Part 1: Prostatic intraepithelial neoplasia.
AB  - What's known on the subject? and What does the study add? In the era of extended
      biopsy sampling of the prostate, multifocal high-grade prostatic intraepithelial
      neoplasia (HGPIN) is associated with a significantly higher rate of cancer
      diagnosis than unifocal HGPIN or a benign diagnosis. In addition, the cancers
      that are subsequently diagnosed in men with HGPIN on their initial biopsy tend to
      be smaller, lower grade and more commonly organ-confined. This has led to a
      reappraisal of the need and timing of repeat biopsies. The present paper provides
      a series of recommendations on the optimal timing of repeat biopsies in men with
      HGPIN on biopsy, based on the current available evidence. This is the first of a
      two part series reviewing the nature and clinical significance of in situ
      cellular proliferations in the prostate gland. This first part examines prostatic
      intraepithelial neoplasia (PIN), while the second part in the next supplement
      discusses intraductal carcinoma and ductal adenocarcinoma of the prostate. PIN is
      a precursor lesion in the development of some forms of adenocarcinoma of the
      prostate. In the 1990 s, high-grade PIN (HGPIN) on biopsy was a significant
      predictor of carcinoma, but this was due to incomplete sampling with sextant
      biopsies. With more extensive sampling in the last decade, the likelihood of
      identifying cancer after a diagnosis of HGPIN is not significantly different from
      a benign diagnosis. In several recent studies, it is now recognised that
      multifocal HGPIN is a better predictor of cancer than unifocal HGPIN. Most cases
      of cancer will be detected in the vicinity of the HGPIN, but up to 40% of cancers
      will occur in different sextants. In assessing potential markers for carcinoma in
      men with HGPIN on biopsy, alpha-methylacyl coenzyme-A racemase (AMACR) has
      emerged as a promising diagnostic tool. HGPIN with strong staining for AMACR is
      associated with a higher rate of cancer detection in subsequent biopsies compared
      with AMACR-negative HGPIN. Also, AMACR positivity in HGPIN is more commonly seen
      adjacent to carcinoma, and this may provide guidance as to the site of future
      biopsies.

PMID- 22458489
TI  - Genitourinary tuberculosis in Australia and New Zealand.
AB  - Genitourinary tuberculosis is not commonly encountered in general urological
      practice in Australia and New Zealand. However, this infection is easily
      overlooked unless clinicians maintain a strong awareness of its possibility. This
      brief overview is directed to reflect the present state of knowledge and
      management in our two countries.

PMID- 22458490
TI  - Diagnosing detrusor sphincter dyssynergia in the neurological patient.
AB  - Detrusor sphincter dyssynergia (DSD) is variant of neurogenic bladder dysfunction
      caused by suprasacral neurological abnormalities and may be associated with
      serious complications if unrecognised. This paper focuses on the clinical
      features as well as challenges and limitations in the diagnosis of DSD.

PMID- 22458491
TI  - Integration of laparoscopic partial nephrectomy into an Australian public
      hospital: three-year follow-up of our initial 50 cases.
AB  - OBJECTIVE: To examine the early outcomes and complications of integrating
      laparoscopic partial nephrectomy (LPN) into a public teaching hospital in
      Australia. PATIENTS AND METHODS: An outcomes review from prospectively collected
      data on our initial 50 cases of LPN. The median follow-up was 36 months with a
      minimum follow-up of 2 years and a maximum of 5 years. RESULTS: The mean patient
      age was 60 years, mean tumour size was 2.9 cm, and mean baseline creatinine
      concentration was 79 umol/L. One patient had a solitary kidney, and one patient
      had bilateral tumours. The mean operative duration was 168 min, with a mean warm
      ischaemia time of 25 min. The median blood loss was 100 mL and the median (range)
      hospital stay was 4 (2-12) days. The complication rate was 6%, including two
      instances of secondary haemorrhage, and one port-site hernia. No patient required
      conversion to radical nephrectomy or experienced clinically significant
      deterioration in their renal function. There have been no local or systemic
      recurrences to date, with a maximum follow-up of 5 years. CONCLUSIONS: LPN can be
      successfully integrated into the Australian public health care sector as standard
      of care for stage 1 renal masses requiring treatment. Due to the inherent risk of
      bleeding early in the learning curve, cases should be performed in the setting of
      adequate surgical and interventional radiographic support.

PMID- 22458492
TI  - Active surveillance for prostate cancer: an Australian experience.
AB  - OBJECTIVE: To assess the patient and cancer characteristics as well as outcomes
      of a large cohort of Australian men who chose active surveillance (AS) as initial
      management of their low-risk prostate cancer. PATIENTS AND METHODS: Men treated
      by one surgeon who had chosen AS as the primary management for prostate cancer
      were identified from the records. The patient and cancer data recorded included:
      patient age, prostate-specific antigen (PSA) concentration at diagnosis, mode of
      prostate cancer detection. For prostate cancer diagnosed at prostate biopsy, data
      were collected for the number of cores taken as well as positive core number,
      cancer burden, and Gleason grade. Survival analysis was used to determine the
      duration of AS. RESULTS: In all, 154 men with low-risk prostate cancer with a
      median (range) age 63.0 (36-81) years and a mean (range) PSA concentration of 6.5
      (0.3-22) ng/mL underwent AS. The median (range) duration of AS was 1.9 (0.1-16.6)
      years. AS was ceased in 29 patients (19%) after a mean (range) of 2.4 (0.2-7.9)
      years. Of these, 26 were upstaged, one chose curative treatment despite stable
      disease, and two died from disease not related to prostate cancer. Actuarial
      analysis on the probability of still being on AS after 5 years was 61.9% (95%
      confidence interval [CI] 46.2-74.2%) and after 10 years was 45.0% (95% CI 21.3
      66.2%). While the period of follow-up is short, there were no biochemical
      recurrences in men who underwent curative treatment and no deaths from prostate
      cancer. CONCLUSION: AS is an acceptable mode of initial treatment in Australian
      men with low-risk prostate cancer.

PMID- 22458493
TI  - Renal lesions with low R.E.N.A.L nephrometry score are associated with more
      indolent renal cell carcinomas (RCCs) or benign histology: findings in an
      Australian cohort.
AB  - OBJECTIVE: To validate the relationship of the R.E.N.A.L nephrometry score to
      histological features of renal lesions treated by surgical excision by radical
      nephrectomy (RN) or nephron-sparing surgery (NSS) at an Australian tertiary
      referral centre. PATIENTS AND METHODS: Patients undergoing surgery between 2005
      and 2009 with imaging studies available were included. The R.E.N.A.L. nephrometry
      score is an objective measure of factors important in determining suitability for
      NSS, e.g. size, exophytic nature, proximity to collecting system and polar
      location, and R.E.N.A.L scoring was done using the online template at
      http://www.nephrometry.com. Pathological details were collected by retrospective
      chart review. Comparisons were made using chi-squared or Fisher's exact tests and
      trends analysed by linear regression. RESULTS: The rate of benign pathology
      decreased from 12/58 (20.7%) low-complexity lesions to 1/16 (6.2%) high
      complexity lesions (P= 0.09), renal cell carcinomas (RCCs) were stable between
      45/58 (77.6%) and 13/16 (81.2%), but other malignancies increased (P= 0.058) from
      1/58 (1.7%) to 2/16 (12.5%). Among the RCCs, high vs low R.E.N.A.L score was
      associated with an increasing risk of clear cell histology (84.6% vs 64.4%, P <
      0.05), stage >= pT3 (76.9% vs 8.9%, P < 0.001) and grade 4 tumours (15.4% vs
      2.2%, P < 0.05), and conversely with a lower risk of papillary histology (0% vs
      24.4%, P < 0.02) and stage T1a (0% vs 84.4%, P < 0.001). CONCLUSIONS: Increasing
      R.E.N.A.L score is associated with histological features of tumour
      aggressiveness, thus reinforcing the need for RN for lesions with a high score,
      and conversely the safety of NSS or observation for lesions with a low score.

PMID- 22458494
TI  - Algorithm for selecting men for pelvic lymph node dissection (PLND) during
      radical prostatectomy based on clinical risk factors in an Australian population.
AB  - OBJECTIVE: To define selection criteria for pelvic lymph node dissection (PLND)
      based on a contemporary Australian cohort of men with clinically localised
      prostate cancer undergoing radical prostatectomy (RP) with PLND, as stage
      migration of prostate cancer has led to re-evaluation of the role of PLND at the
      time of RP. PATIENTS AND METHODS: In all, 200 consecutive men treated by one
      surgeon between 2000 and 2005 with open RP and PLND. The clinical and
      pathological data were extracted by retrospective chart review. Associations
      between clinical predictors and LN positivity were assessed by logistic
      regression analysis. RESULTS: Overall, there were LN metastases were in 10 (5%)
      men. The LN positivity rate was significantly associated with biopsy Gleason
      score, preoperative prostate-specific antigen (PSA) concentration and percentage
      of positive cores (PPC), with respective odds ratios (OR) (95% confidence
      interval [CI]) of 3.70 (1.98-6.92), 1.11 (1.04-1.19) and 1.04 (1.01-1.06) Trend
      toward significant association with clinical stage (OR 1.75, 95% CI 0.97-3.13) On
      multivariate analysis, PSA concentration and biopsy Gleason score were
      significant predictors of LN disease. All 10 men with LN metastases came from a
      high-risk group of 96, identifiable by having at least one of the following:
      stage >= cT2b, biopsy Gleason score >= 4+3, PSA concentration of >= 10 ng/mL or
      PPC of >= 38%. CONCLUSIONS: The risk of LN metastases depends upon well-defined
      clinical risk factors of stage, biopsy Gleason score, PSA concentration and PPC.
      The present data suggests a simple risk-stratification method, using these risk
      factors, of identifying men to have PLND at the time of RP.

PMID- 22458495
TI  - Patient knowledge about prostate-specific antigen (PSA) and prostate cancer in
      Australia.
AB  - OBJECTIVE: To assess whether men undergoing prostate biopsies for raised prostate
      specific antigen (PSA) concentrations were adequately counselled before their
      first PSA test. PATIENTS AND METHODS: Men were given a PSA information sheet and
      interviewed immediately before undergoing transrectal ultrasonography
      (TRUS)/prostate biopsy. Information collected included whether they had been
      informed of the test, whether they were aware of TRUS/biopsy and whether possible
      treatments for prostate cancer had been discussed. They were asked whether the
      information sheet would have changed their opinion on testing. RESULTS: 50 men
      were interviewed and 48 had their first test arranged by their general
      practitioner. 12.5% of men were adequately counselled using recently defined
      criteria. 4 (8.3%) men would not have had a PSA test if they had received
      adequate prior information CONCLUSIONS: Counselling before serum PSA testing
      remains inadequate. Patient information sheets may help the discussions and
      should be made more widely available.

PMID- 22458496
TI  - Prostate weight is the preferred measure of prostate size in radical
      prostatectomy cohorts.
AB  - OBJECTIVE: To evaluate the accuracy of calculated prostate volume variables in a
      radical prostatectomy (RP) cohort, as many recent studies use these measures of
      prostate size instead of prostate weight. To determine whether this accuracy
      could be improved by modifying the mathematical model used in the volume
      estimation. PATIENTS AND METHODS: Patients who underwent RP for prostate cancer
      at our associated institutions had calculated specimen volumes and weights from
      RP specimens determined at one pathology institution and transrectal
      ultrasonography (TRUS) volumes were recorded preoperatively (n= 236). Correlation
      analysis was performed and errors were determined for calculated volume variables
      when compared with prostate weight. Bland-Altman plots were drawn and concordance
      coefficients calculated. Analysis was repeated with smaller prostates
      mathematically modelled as bullet-shaped rather than ellipsoid (n= 165). RESULTS:
      Although correlation was good for both TRUS and specimen volumes, they equally
      underestimated prostate weight with a large range of errors and poor concordance
      coefficients. Only 22% of TRUS volumes and 11% of calculated specimen volumes
      were within 10% of weight measurements. Application of a bullet-shaped
      mathematical model for prostates <55 g did not correct the large individual
      variation seen within these values. CONCLUSION: Calculated prostate volume
      variables are prone to a large range of individual error regardless of the
      mathematical model used and should be avoided in statistical studies involving RP
      cohorts, and the more accurate prostate weight variable should instead be used as
      a size variable or correction factor.

PMID- 22458497
TI  - Patterns of prostate-specific antigen (PSA) testing in Australian men: the
      influence of family history.
AB  - OBJECTIVE: To describe how a family history of prostate cancer influences men's
      prostate cancer testing behaviours, information support preferences, and motives
      for testing. SUBJECTS AND METHODS: Men with a first-degree family history (239
      men) and a comparison sample from the general population of Queensland, Australia
      (289) aged 40-65 years, and no prior history of cancer. Cross-sectional,
      retrospective survey assessing: prevalence of prostate-specific antigen (PSA)
      testing and digital rectal examination (DRE); discussion of prostate cancer risks
      and benefits with a physician; prostate cancer information needs and preferences;
      motivations for testing. RESULTS: Men with a family history were more likely to
      report: having ever had a PSA test (odds ratio [OR] 4.98; 95% confidence interval
      [CI] 3.16-7.85), more PSA tests in their lifetimes (b 1.04; se 0.40; 95% CI 0.26
      1.82); to have had a DRE (OR 2.23; 95% CI 1.54-3.23); to have spoken to a doctor
      about prostate cancer (OR 3.72; 95% CI 2.30-6.02); and to have instigated these
      discussions (OR 1.74; 95%CI 1.13-2.70). Most men from both groups did not recall
      any discussion of the 'cons' of prostate cancer testing with a doctor. Men with a
      family history reported a greater desire for information about prostate cancer
      prevention than did men without a family history. CONCLUSIONS: Men with a family
      history are more concerned about getting prostate cancer and are tested more
      often; however, information needs, discussions about prostate cancer, and
      motivations for testing are similar to those of all men. There appears to be a
      disparity between public health approaches that promote informed decision-making
      and what is happening in practice.

PMID- 22458498
TI  - Re: Prostate cancer incidence in Australia correlates inversely with solar
      radiation.

PMID- 22458499
TI  - Re: Prostate cancer incidence in Australia correlates inversely with solar
      radiation.

PMID- 22458501
TI  - The value and limitations of transgenic mouse models used in drug discovery for
      Alzheimer's disease: an update.
AB  - INTRODUCTION: The exponential growth in the world's aged population has increased
      pressure on drug discovery efforts to identify innovative therapies for
      Alzheimer's disease (AD). The long and uncertain clinical trial path utilized to
      test the potential efficacy of these novel agents is challenging. For these and
      other reasons, there has been an explosion in the generation and availability of
      transgenic mouse models that mimic some, but not all aspects of AD. The largely
      overwhelmingly positive results obtained when testing potential clinical agents
      in these same animal models have failed to translate into similar positive
      clinical outcomes. AREAS COVERED: This review discusses the value and limitations
      associated with currently available transgenic mouse models of AD. Furthermore,
      the article proposes ways in which researchers can better characterize
      pharmacodynamic and pharmacokinetic endpoints to increase the success rate for
      novel therapies advancing into clinical development. Lastly, the author discusses
      ways in which researchers can supplement, expand and improve transgenic mouse
      models used in AD drug discovery. EXPERT OPINION: The use of transgenic mouse
      models that recapitulate various aspects of AD has expanded our knowledge and
      understanding of disease pathogenesis immensely. Further success in testing and
      translating novel therapies from animal models into bona fide medicines would be
      enhanced by i) the availability of better models that more fully recapitulate the
      disease spectrum, ii) defining and measuring standardized endpoints that display
      a pharmacodynamic range, iii) building and including translatable biomarkers and
      iv) including novel endpoints that would be expected to translate into clinically
      beneficial outcomes.

PMID- 22458502
TI  - Thermodynamic studies for drug design and screening.
AB  - INTRODUCTION: A key part of drug design and development is the optimization of
      molecular interactions between an engineered drug candidate and its binding
      target. Thermodynamic characterization provides information about the balance of
      energetic forces driving binding interactions and is essential for understanding
      and optimizing molecular interactions. AREAS COVERED: This review discusses the
      information that can be obtained from thermodynamic measurements and how this can
      be applied to the drug development process. Current approaches for the
      measurement and optimization of thermodynamic parameters are presented,
      specifically higher throughput and calorimetric methods. Relevant literature for
      this review was identified in part by bibliographic searches for the period 2004 
      2011 using the Science Citation Index and PUBMED and the keywords listed below.
      EXPERT OPINION: The most effective drug design and development platform comes
      from an integrated process utilizing all available information from structural,
      thermodynamic and biological studies. Continuing evolution in our understanding
      of the energetic basis of molecular interactions and advances in thermodynamic
      methods for widespread application are essential to realize the goal of
      thermodynamically driven drug design. Comprehensive thermodynamic evaluation is
      vital early in the drug development process to speed drug development toward an
      optimal energetic interaction profile while retaining good pharmacological
      properties. Practical thermodynamic approaches, such as enthalpic optimization,
      thermodynamic optimization plots and the enthalpic efficiency index, have now
      matured to provide proven utility in the design process. Improved throughput in
      calorimetric methods remains essential for even greater integration of
      thermodynamics into drug design.

PMID- 22458503
TI  - New drug discovery strategies for rheumatoid arthritis: a niche for nonhuman
      primate models to address systemic complications in inflammatory arthritis.
AB  - INTRODUCTION: Despite the tremendous advances made in the treatment of rheumatoid
      arthritis (RA), there is still excess mortality observed in RA patients, which is
      mainly caused by cardiovascular disease (CVD). Altered lipid metabolism plays a
      major role in the etiology of CVD. A second common complication observed in RA
      patients is anemia. Both conditions are serious, reduce quality of life and are
      undertreated. AREAS COVERED: The authors postulate that there is a specific niche
      for nonhuman primate models of inflammatory arthritis to address these systemic
      complications that occur in RA. Furthermore, the authors postulate that these
      nonhuman primate models are a useful platform to unveil the mechanisms underlying
      dyslipidemia and anemia, which are responsible for the manifestation of these
      complications. EXPERT OPINION: The presence of currently untreated systemic
      complications of RA, such as dyslipidemia and anemia, provides interesting
      opportunities to include these in the preclinical evaluation of new therapies. In
      the selection of relevant models for the evaluation of new treatments for RA or
      the identification of new targets for therapy, we postulate that nonhuman
      primates should be considered as a valid preclinical model. Because of their
      closer immunological and physiological proximity to humans, these models in
      nonhuman primates can be valuable for studying disease-related aspects that
      cannot be addressed in rodent models.

PMID- 22458504
TI  - Bacterial DNA replication enzymes as targets for antibacterial drug discovery.
AB  - INTRODUCTION: The bacterial replisome is composed of a large number of enzymes,
      which work in exquisite coordination to accomplish chromosomal replication.
      Effective inhibition inside the bacterial cell of any of the 'essential' enzymes
      of the DNA replication pathway should be detrimental to cell survival. AREAS
      COVERED: This review covers DNA replication enzymes that have been shown to have
      a potential for delivering antibacterial compounds or drug candidates including:
      type II topoisomerases, a clinically validated target family, and DNA ligase,
      which has yielded inhibitors with in vivo efficacy. A few of the 'replisome'
      enzymes that are structurally and functionally well characterized and have been
      subjects of antibacterial discovery efforts are also discussed. EXPERT OPINION:
      Identification of several essential genes in the bacterial replication pathway
      raised hopes that targeting these gene products would lead to novel
      antibacterials. However, none of these novel, single gene targets have delivered
      antibacterial drug candidates into clinical trials. This lack of productivity may
      be due to the target properties and inhibitor identification approaches employed.
      For DNA primase, DNA helicase and other replisome targets, with the exception of
      DNA ligase, the exploitation of structure for lead generation has not been tested
      to the same extent that it has for DNA gyrase. Utilization of structural
      information should be considered to augment HTS efforts and initiate fragment
      based lead generation. The complex protein-protein interactions involved in
      regulation of replication may explain why biochemical approaches have been less
      productive for some replisome targets than more independently functioning targets
      such as DNA ligase or DNA gyrase.

PMID- 22458505
TI  - Decision tree models for data mining in hit discovery.
AB  - INTRODUCTION: Decision tree induction (DTI) is a powerful means of modeling data
      without much prior preparation. Models are readable by humans, robust and easily
      applied in real-world applications, features that are mutually exclusive in other
      commonly used machine learning paradigms. While DTI is widely used in disciplines
      ranging from economics to medicine, they are an intriguing option in
      pharmaceutical research, especially when dealing with large data stores. AREAS
      COVERED: This review covers the automated technologies available for creating
      decision trees and other rules efficiently, even from large datasets such as
      chemical libraries. The authors discuss the need for properly documented and
      validated models. Lastly, the authors cover several case studies in hit
      discovery, drug metabolism and toxicology, and drug surveillance, and compare
      them with other established techniques. EXPERT OPINION: DTI is a competitive and
      easy-to-use tool in basic research as well as in hit and drug discovery. Its
      strengths lie in its ability to handle all sorts of different data formats, the
      visual nature of the models, and the small computational effort needed for
      implementation in real-world systems. Limitations include lack of robustness and
      over-fitted models for certain types of data. As with any modeling technique,
      proper validation and quality measures are of utmost importance.

PMID- 22458506
TI  - Use of cysteine-reactive small molecules in drug discovery for trypanosomal
      disease.
AB  - INTRODUCTION: The roles of cysteine protease (CP) enzymes in the biochemistry and
      infectivity of the three trypanosomal parasitic infections, Chagas' disease,
      leishmaniasis and human African trypanosomiasis, which have been elucidated over
      the last three decades are summarized. Inhibitors of these enzymes, which act
      through trapping the active site cysteine with an electrophilic warhead, hold
      huge potential as therapeutic agents but the promise of these has yet to be
      realized in clinical studies. The article addresses aspects that ought to be
      considered in order to develop orally active CP inhibitors that are safe and
      effective therapies for trypanosomiasis. AREAS COVERED: This article reviews
      learnings from CP research in the trypanosomal field and recent advances in
      developing cysteine protease inhibitors (CPIs) of human cathepsin K, a related
      enzyme. Considerations such as intra- and extracellular localization of the CPs,
      off-target activities against human cathepsin enzymes, basic versus neutral and
      potential pro-drug inhibitors are reviewed. A description of odanacatib, a
      cathepsin K inhibitor currently in late stage development, is made to illustrate
      the attributes of a clinically viable CPI. EXPERT OPINION: The emerging role of
      CPs in a wide array of parasitic diseases is highlighted with the vision that CP
      inhibitors could become the 'beta-lactams' of anti-parasitic treatments in the
      coming decades. New CPI research will see the optimization of intra- and
      extracellular enzyme targeting, reduction of off-target activities and better
      understanding of pharmacokinetic-pharmacodynamic interactions which will all lead
      to compounds with much improved efficacy and viability as clinical therapies.

PMID- 22458507
TI  - Safety and efficacy assessment of standardized herbal formula PM012.
AB  - BACKGROUND: This study was conducted to evaluate the efficacy of the herbal
      formula PM012 on an Alzheimer's disease model, human presenilin 2 mutant
      transgenic mice (hPS2m), and also to evaluate the toxicity of PM012 in Sprague
      Dawely rats after 4 or 26 weeks treatment with repeated oral administration.
      METHODS: Spatial learning and memory capacities of hPS2m transgenic mice were
      evaluated using the Morris Water Maze. Simultaneously, PM012 was repeatedly
      administered orally to male and female SD rats (15/sex/group) at doses of 0
      (vehicle control), 500, 1,000 and 2,000 mg/kg/day for 4 or 26 weeks. To evaluate
      the recovery potential, 5 animals of each sex were assigned to vehicle control
      and 2,000 mg/kg/day groups during the 4-week recovery period. RESULTS: The
      results showed that PM012-treated hPS2m transgenic mice showed significantly
      reduced escape latency when compared with the hPS2m transgenic mice. The repeated
      oral administration of PM012 over 26 weeks in male and female rats induced an
      increase and increasing trend in thymus weight in the female treatment groups
      (main and recovery groups), but the change was judged to be toxicologically
      insignificant. In addition, the oral administration of the herbal medicine PM012
      did not cause adverse effects as assessed by clinical signs, mortality, body
      weight, food and water consumption, ophthalmology, urinalysis, hematology, serum
      biochemistry, blood clotting time, organ weights and histopathology. The No
      Observed Adverse Effects Levels of PM012 was determined to be 2,000 mg/kg/day for
      both sexes, and the target organ was not identified. CONCLUSION: These results
      suggest that PM012 has potential for use in the treatment of the Alzheimer's
      disease without serious adverse effects.

PMID- 22458508
TI  - Simultaneous renal hypertension and type 2 diabetes exacerbate vascular
      endothelial dysfunction in rats.
AB  - Despite the high rate of occurrence of both diabetes and hypertension in humans,
      the cardiovascular effects of the two conditions have not been investigated when
      they occur simultaneously. Thus this study examined the vascular effects of
      simultaneous type 2 diabetes and renal hypertension on endothelial function.
      Serum malondialdehyde and systolic blood pressure (SBP) were measured, glucose
      tolerance test (GTT) was performed, and concentration-response to phenylephrine
      (PE) in the absence and presence of nitro-l-arginine methyl ester (l-NAME),
      acetylcholine and sodium nitroprusside were conducted on aortic rings from
      diabetic control, type 2 diabetes, sham-operated, renal hypertensive, and
      simultaneous type 2 diabetes plus hypertension rats respectively. Hypertension,
      diabetes, and simultaneous diabetes and hypertension were associated with either
      increased or decreased maximal responses (E(max)) of PE dependent on in the
      presence or absence of l-NAME. There was also increased serum malondialdehyde and
      decreased E(max) of acetylcholine. Thus simultaneous hypertension and diabetes
      caused a greater decrease in E(max) of acetylcholine compared to that seen with
      either diabetes or hypertension alone higher than that seen in hypertension. The
      blood glucose during GTT was lower than that seen in diabetes groups. Thus
      simultaneous type 2 diabetes and the SBP was renal hypertension is associated
      with improved glucose tolerance, but with further deterioration of endothelial
      dysfunction compared with either condition alone.

PMID- 22458509
TI  - Multifocal skin basal cell carcinomata 57 years after topical dry ice treatment.
AB  - We report a rare case of simultaneous multiple basal cell carcinomata occurring
      on the back of a patient who had received dry ice treatment to this area almost 6
      decades previously. This is also one of the longest recorded disease-free
      intervals between skin trauma and basal cell carcinoma development. We discuss
      the aetiopathology of multiple skin cancers in our patient and the propensity for
      destructive skin events to predispose to malignancy. 

PMID- 22458510
TI  - Bone as target organ for metals: the case of f-elements.
AB  - The skeleton is a target organ for most metals. This leads to their
      bioaccumulation, either as storage of useful oligoelements or as a protection
      against damage by toxic elements. The different events leading to their
      accumulation in this organ, under constant remodeling, are not fully understood,
      nor the full subsequent impact on bone metabolism. This lack of knowledge is
      particularly true for lanthanides and actinides, whose use has been increasing
      over recent decades. These metals, known as f-elements, present chemical
      similarities and differences. After a comparison of the biologically relevant
      physicochemical properties of lanthanides and actinides, and a brief reminder of
      the main events of bone metabolism, this review considers the results published
      over the past decade regarding the interaction between bones and f-elements.
      Emphasis will be given to the molecular events, which constitute the basis of the
      most recent toxicological studies in this domain but still need further
      investigation. Ionic exchanges with the inorganic matrix, interactions with bone
      proteins, and cellular mechanism disturbances are mainly considered in this
      review.

PMID- 22458511
TI  - Clinical ex vivo lung perfusion--pushing the limits.
AB  - Ex vivo lung perfusion (EVLP) provides the ability to evaluate donor lungs before
      transplantation. Yet, limited prospective clinical data exist with regard to its
      potential to recondition unacceptable donor lungs. This paper summarizes the
      results of a prospective study of lung transplantation using only initially
      unacceptable donor lungs, which were improved by EVLP for 2-4 h. From March 2010
      June 2011, 13 lungs were evaluated ex vivo. Median donor PaO(2)  at FiO(2)
      1.0/PEEP5 was 216 mmHg (range 133-271). Four lungs, all with trauma history,
      showed no improvement and were discarded. Nine lungs improved to a DeltaPO(2) 
      higher than 350 mmHg. Median PvO(2)  at final assessment in these lungs was 466
      mmHg (range 434-525). These lungs were transplanted with a median total ischemic
      time of 577 min (range 486-678). None of the patients developed primary graft
      dysfunction grades 2 or 3 within 72 h after transplantation. One patient with
      secondary pulmonary hypertension was left on a planned prolonged extracorporeal
      membrane oxygenation postoperatively. Median intubation time was 2 days. Thirty
      day mortality was 0%. During the observation period, 119 patients received
      standard lung transplantation with comparable perioperative outcome. EVLP has a
      significant potential to improve the quality of otherwise unacceptable donor
      lungs.

PMID- 22458513
TI  - Nucleophilic addition-triggered lanthanide luminescence allows detection of
      amines by Eu(thenoyltrifluoroacetone)3.
AB  - Herein, a novel fluorescent indicator for the real-time monitoring of amines is
      described. This probe contains a complex of europium-(thenoyltrifluoroacetone)(3)
      (Eu(TTA)(3)) that efficiently reacts with primary and secondary amines. The
      electron-withdrawing trifluoroacetyl undergoes a nucleophilic addition with
      amines, and the complex was used to selectively detect BuNH(2) and Et(2) NH
      (quenching concentration for BuNH(2): 10(-4) M, for Et(2)NH: 1.2 * 10(-3) M) by
      monitoring emission; no changes were observed in the emission spectrum of
      Eu(TTA)(3) in the presence of Et(3)N, [Bu(4)N]Cl, or PhNH(2) in aqueous solution
      (THF/H(2)O = 1:1). The ratio of emission intensity to amine concentration was
      linear by the least-squares fitting method.

PMID- 22458512
TI  - The generation of vertebral segmental patterning in the chick embryo.
AB  - We have carried out a series of experimental manipulations in the chick embryo to
      assess whether the notochord, neural tube and spinal nerves influence segmental
      patterning of the vertebral column. Using Pax1 expression in the somite-derived
      sclerotomes as a marker for segmentation of the developing intervertebral disc,
      our results exclude such an influence. In contrast to certain teleost species,
      where the notochord has been shown to generate segmentation of the vertebral
      bodies (chordacentra), these experiments indicate that segmental patterning of
      the avian vertebral column arises autonomously in the somite mesoderm. We suggest
      that in amniotes, the subdivision of each sclerotome into non-miscible anterior
      and posterior halves plays a critical role in establishing vertebral
      segmentation, and in maintaining left/right alignment of the developing vertebral
      elements at the body midline.

PMID- 22458514
TI  - Methanogenic activity and diversity in the centre of the Amsterdam Mud Volcano,
      Eastern Mediterranean Sea.
AB  - Marine mud volcanoes are geological structures emitting large amounts of methane
      from their active centres. The Amsterdam mud volcano (AMV), located in the
      Anaximander Mountains south of Turkey, is characterized by intense active methane
      seepage produced in part by methanogens. To date, information about the diversity
      or the metabolic pathways used by the methanogens in active centres of marine mud
      volcanoes is limited. (14)C-radiotracer measurements showed that
      methylamines/methanol, H(2)/CO(2) and acetate were used for methanogenesis in the
      AMV. Methylotrophic methanogenesis was measured all along the sediment core,
      Methanosarcinales affiliated sequences were detected using archaeal 16S PCR-DGGE
      and mcrA gene libraries, and enrichments of methanogens showed the presence of
      Methanococcoides in the shallow sediment layers. Overall acetoclastic
      methanogenesis was higher than hydrogenotrophic methanogenesis, which is unusual
      for cold seep sediments. Interestingly, acetate porewater concentrations were
      extremely high in the AMV sediments. This might be the result of organic matter
      cracking in deeper hotter sediment layers. Methane was also produced from
      hexadecanes. For the most part, the methanogenic community diversity was in
      accordance with the depth distribution of the H(2)/CO(2) and acetate
      methanogenesis. These results demonstrate the importance of methanogenic
      communities in the centres of marine mud volcanoes.

PMID- 22458516
TI  - Au-catalyzed asymmetric formal [3 + 2] cycloaddition of isocyanoacetates with
      maleimides.
AB  - An efficient protocol for the Au(I)-catalyzed asymmetric formal [3 + 2]
      cycloaddition of isocyanoacetates with phenylmaleimide has been developed. In the
      presence of cationic Au(I)/DTBM-segphos complex, excellent diastereoselectivity
      and high levels of enantioselectivity (up to 97% ee) have been attained with a
      variety of alpha-substituted isocyanoacetates. The synthetic potential of the
      resulting enantioenriched 1-pyrrolines has been demonstrated by the preparation
      of highly substituted pyrrolidines bearing a quaternary stereocenter.

PMID- 22458517
TI  - Biofunctionalization of the implant surface with different concentrations of a
      synthetic peptide (P-15).
AB  - OBJECTIVE: This study aimed at identifying the ideal concentration of a
      biofunctional surface coating of dental implants with a synthetic peptide (P-15).
      In a previous study, P-15 was shown to enhance osseointegration parameters.
      MATERIAL AND METHODS: Implants (modified ANKYLOS((r)) A8; FRIADENT Plus((r))
      surface) with five different concentrations (0-400 MUg/ml) of a P-15 coating as
      well as uncoated controls were inserted in the frontal bone of 45 adult domestic
      pigs. The histomorphometric and microradiographic findings for the coated
      implants were compared to those for the uncoated ones after 7, 14, and 30 days.
      RESULTS: No significant differences were observed comparing the peri-implant bone
      density between the coated and uncoated implants The bone-to-implant contact, as
      the primary histological parameter for osseointegration, showed high rates for
      all surfaces investigated (between 73.3 +/- 17.9% for the control and 81.9 +/-
      15.2% for P15 20 MUg/ml after 30 days). CONCLUSIONS: No significant benefit on
      osseointegration of a biofunctional P-15 coating of dental implants could be
      displayed in the present study.

PMID- 22458518
TI  - Pancreatic cancer: between bench and bedside.

PMID- 22458515
TI  - The transcription factor encyclopedia.
AB  - Here we present the Transcription Factor Encyclopedia (TFe), a new web-based
      compendium of mini review articles on transcription factors (TFs) that is founded
      on the principles of open access and collaboration. Our consortium of over 100
      researchers has collectively contributed over 130 mini review articles on
      pertinent human, mouse and rat TFs. Notable features of the TFe website include a
      high-quality PDF generator and web API for programmatic data retrieval. TFe aims
      to rapidly educate scientists about the TFs they encounter through the delivery
      of succinct summaries written and vetted by experts in the field. TFe is
      available at http://www.cisreg.ca/tfe.

PMID- 22458519
TI  - Molecular and genetic bases of pancreatic cancer.
AB  - Pancreatic cancer remains a formidable challenge for oncologists and patients
      alike. Despite intensive efforts, attempts at improving survival in the past 15
      years, particularly in advanced disease, have failed. This is true even with the
      introduction of molecularly targeted agents, chosen on the basis of their action
      on pathways that were supposedly important in pancreatic cancer development and
      progression: indeed, with the notable exception of the epidermal growth factor
      receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival
      improvement when added to gemcitabine, other agents targeting EGFR, matrix
      metallo-proteases, farnesyl transferase, or vascular endothelial growth factor
      have not succeeded in improving outcomes over standard gemcitabine monotherapy
      for a variety of different reasons. However, recent developments in the molecular
      epidemiology of pancreatic cancer and an ever evolving understanding of the
      molecular mechanisms underlying pancreatic cancer initiation and progression
      raise renewed hope to find novel, relevant therapeutic targets that could be
      pursued in the clinical setting. In this review we focus on molecular
      epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its
      influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia
      related pathways, developmental pathways (such as the hedgehog and Notch
      pathways), and proteomic analysis as keys to a better understanding of pancreatic
      cancer biology and, most importantly, as a source of novel molecular targets to
      be exploited therapeutically.

PMID- 22458521
TI  - Is preoperative endoscopic biliary drainage indicated for jaundiced patients with
      resectable pancreatic cancer?
AB  - The role of preoperative biliary drainage (PBD) in the management of jaundiced
      patients with resectable pancreatic cancer (RPC) is controversial. Obstructive
      jaundice determines hepatic dysfunction which can increase the operative risks.
      Experimental studies demonstrated that PBD could be associated with improved
      surgical outcomes. However, clinical studies did not confirm these findings.
      Initial clinical studies conducted with percutaneous approach failed to
      demonstrate a real advantage for patients undergoing PBD before
      pancreaticoduodenectomy. Overall morbidity was higher in patients undergoing PBD,
      because of procedure-related complications. Similar results were obtained with
      endoscopic PBD. Six meta-analyses have not clarified the role of PBD in the
      management of patients with malignant jaundice undergoing
      pancreaticoduodenectomy, because of lack of uniformity among all the studies
      published. Recently, the results of a large randomized controlled trial indicated
      that direct surgery should be the best therapeutic strategy for jaundiced
      patients with RPC. The debate whether jaundiced patients with RPC should undergo
      PBD continues and the advent of neoadjuvant chemoradiotherapy added some
      arguments in favor of PBD. The latter is still considered the first step for
      jaundiced patients when they present with cholangitis, intense pruritus or severe
      jaundice; surgery cannot be scheduled within 7-10 days from the diagnosis;
      neoadjuvant chemoradiation is planned, as part of the treatment. While endoscopic
      PBD is considered the preferred approach, there is still controversy about the
      type of biliary stent which should be used. Emerging data support the insertion
      of short (4-6 cm) biliary self-expandable metallic stent, especially if surgery
      is not immediately planned.

PMID- 22458520
TI  - Molecular pathology of pancreatic cancer: from bench-to-bedside translation.
AB  - Pancreatic ductal adenocarcinoma (referred here as pancreatic cancer) is a lethal
      disease with the worst prognosis among all solid tumors. Surgical resection
      represents the only hope for cure but it is possible only in patients that
      present with local disease (about 20% of cases). Whether dismal prognosis of
      pancreatic cancer is a result of late diagnosis or early dissemination to distant
      organ is still a debate. Moreover, this disease shows an intrinsic
      chemotherapeutic resistance that has been mainly ascribed to the presence of a
      dense stromal reaction that significantly impairs drugs delivery. Clinical
      management of pancreatic cancer patients relies on few molecular markers (e.g.,
      the diagnostic marker CA19-9) that, however, present several limitations to their
      use. The clinical usefulness of somatic alterations in well-characterized genes
      (such as KRAS and TP53), whose detection is technically feasible in different
      biological samples, has been extensively investigated leading to inconsistent
      results. Furthermore, none of the candidate molecular markers identified in
      recent years has shown an appropriate clinical performance and therefore none is
      routinely used. This depicts a scenario where the identification of novel and
      effective clinical biomarkers is mandatory. Very recent genome-wide comprehensive
      studies have shed light on the high degree of genetic complexity and
      heterogeneity of the pancreatic cancers. Although far from being introduced into
      the clinical settings, results from those studies are expected to change
      definitively the perspective through which we look at the clinical management of
      pancreatic cancer patients towards a personalized cancer medicine.

PMID- 22458522
TI  - Pancreatic cancer surgery: the state of the art.
AB  - Pancreatic cancer patients have an extremely poor survival prognosis, and
      surgical resection remains the only curative treatment. Greater experience in
      pancreatic surgery and developments in surgical techniques have reduced surgical
      mortality and morbidity rates. It has been suggested that experienced
      pancreaticoduodenectomy centers should have mortality rates of less than 5% and
      major complication rates of less than 40%. Surgical resection followed by
      combined adjuvant therapy is currently the standard treatment for resectable
      pancreas cancer. Patients with borderline or marginal resectable tumors are
      beginning to have favorable outcomes following neoadjuvant chemotherapy or
      chemoradiation. A number of prospective randomized trials have concluded that
      "extended" pancreaticoduodenectomy for pancreatic head cancer, involving radical
      dissection of lymph nodes and peripancreatic soft tissue, does not appear to
      provide any survival benefits compared with "standard" pancreaticoduodenectomy.
      Conversely, extensive surgery for pancreatic tail or body cancer (i.e., radical
      antegrade modular pancreatosplenectomy) can result in favorable R0 resection
      rates and survival outcomes. However, more prospective randomized trial data are
      required before these conclusions can be considered established. Laparoscopic
      approaches are being increasingly used in the field of pancreatic tumor surgery.
      Moreover, robotic-assisted laparoscopic surgery has also been tried in some
      expert centers. Again, at present a lack of outcome data prevent any definitive
      conclusion at this stage on the usefulness of those approaches compared to
      standard open approaches. Finally, a major problem hindering efforts to identify
      optimal surgical treatment modalities for pancreas cancer is the lack of a clear
      definition and standardization of surgical procedures and pathologic
      descriptions. The American Hepato- PancreatoBiliary Association/Society of
      Surgical Oncology/Society for Surgery of the Alimentary Tract conference on
      pancreatic cancer held in 2008 resulted in a consensus statement as an important
      first step in overcoming this fundamental hurdle.

PMID- 22458523
TI  - Vascular resection in pancreaticoduodenectomy: is it worthwhile?
AB  - Pancreaticoduodenectomy (PD) is the gold standard treatment for cancer of
      pancreatic head in all the cases that are supposed to be resectable. Although the
      overall survival depends on many heterogeneous factors, the main aim of the
      treatment must be to achieve a R0 resection with microscopically and
      macroscopically free margins. As in recent reports vascular involvement does not
      represent anymore a technical limit, it is mandatory pointing out whether or not
      vascular resection modifies overall survival and if that is the case vascular
      invasion should not be considered as an exclusion criterion but as part of a
      standard resection. The review analysis demonstrated a progressive trend of
      inversion in the treatment of head pancreatic cancer over the last years.
      Recently, provided that a R0 resection may be performed, a more aggressive
      surgical approach has led to consider the possibility of venous and arterial
      resections. The basis for this new approach has been that the superior mesenteric
      vein or spleno-portal mesenteric vein invasion is not a measure of the tumor
      malignancy but merely a consequence of the tumor location. On the contrary, the
      controversial results in terms of overall survival and local recurrences achieved
      with major arterial resections are more likely due to a biological aggressivity
      than to the tumor site. The "artery first" technique seems to be the most
      promising approach to the problem although it needs further trials to determine
      whether or not this approach may be beneficial for patients in terms of overall
      survival and local recurrences.

PMID- 22458524
TI  - Neoadjuvant therapy for resectable and borderline resectable adenocarcinoma of
      the pancreas.
AB  - For over 25 years, the standard of care for resectable pancreatic adenocarcinoma
      has been upfront surgery followed by delivery of post-operative therapy. Until
      recently however, there has been no consensus as what constituted a standard
      adjuvant regimen. Data from large phase III studies now support single agent
      gemcitabine, administered over 6 cycles, as standard. Nevertheless, the overall
      survival of patients undergoing upfront surgical resection followed by adjuvant
      therapy remains poor, with no significant improvements in median, or long term
      survival over the last 3 decades. Surgery as the first intervention for
      potentially curative pancreatic cancer has some distinct disadvantages and
      neoadjuvant therapy provides a mechanism to better select patients for subsequent
      surgical intervention. Current data suggest this approach spares patients from a
      morbid surgical procedure when it will be of no benefit and improves outcomes for
      those who do undergo surgery. Furthermore, with the increasing recognition of
      borderline resectable pancreatic cancer, neoadjuvant treatment should be
      considered as alternative to upfront surgery for this distinct clinical entity.
      This has the potential to maximize the chances of a margin-negative resection and
      minimize the number of patients harboring aggressive disease from undergoing a
      fruitless surgical procedure. Importantly, as the number of targeted agents
      available for clinical use expands, more rational, personalized neoadjuvant
      therapies may emerge.

PMID- 22458525
TI  - Evidences and opinions for adjuvant therapy in pancreatic cancer.
AB  - Pancreatic adenocarcinoma is a rare tumor with a very poor outcome. Even with
      surgery, 5-year overall survival is less than 10%, due to the propensity of the
      disease for local and systemic recurrence. Adjuvant chemoradiotherapy and
      systemic chemotherapy were assessed in prospective trials in order to improve
      disease control and patients' prognosis. However, due to the difficulty of
      performing prospective trials in a rare disease; to the progress in surgical and
      radiotherapic techniques; and to the availability of novel anti-cancer agents,
      the existing information on the best possible management of patients with
      resectable disease is limited and becomes rapidly obsolete. Accordingly and also
      due to some contradictory findings from randomized trials, the topic of optimal
      adjuvant therapy for this disease encompasses several areas of controversy. The
      present review reports the main opinions on the role of adjuvant
      chemoradiotherapy, adjuvant chemotherapy, best single agent, and combination
      chemotherapy. Data from randomized trials are presented and critically analyzed
      to identify the available evidence supporting the different therapeutic choices
      and the main methodological drawbacks hampering the proper interpretation of
      results. Single agent chemotherapy yields a clinically significant, albeit
      modest, improvement in overall survival and may represent a standard option. The
      role of combination chemotherapy warrants further investigation and the impact of
      adjuvant chemoradiation both on local control and on the final outcome is
      uncertain. The need for more active and effective systemic treatments, for a
      better knowledge of the disease biology, for new therapeutic agents and
      predictors of pattern of recurrence is evident.

PMID- 22458526
TI  - Conventional chemotherapy of advanced pancreatic cancer.
AB  - The vast majority of patients with pancreatic cancer present with locally
      advanced unresectable or metastatic disease, and in this setting only a
      palliative treatment can be offered. Single-agent gemcitabine has been considered
      the standard chemotherapy for patients with advanced pancreatic cancer since the
      results of a pivotal phase III trial showing superior clinical benefit compared
      to bolus 5-fluorouracil were published in 1997. In recent years, many randomized
      trials have attempted to improve results obtained with gemcitabine exploring a
      different schedule (fixed dose rate) of its administration, or testing the
      addition of one or more drugs to gemcitabine. Unfortunately, none of these trials
      produced a statistically significant and clinically relevant improvement in
      overall survival compared to the standard. A randomized phase III trial has
      recently shown a survival advantage using a combination of more drugs
      (FOLFIRINOX: irinotecan, oxaliplatin, folinic acid and 5-fluorouracil) compared
      to single-agent gemcitabine, suggesting that regimens without gemcitabine can be
      successfully used in patients with advanced pancreatic cancer. FOLFIRINOX was
      associated with worse toxicity than gemcitabine, and the available data suggest
      that this regimen may be considered for patients with metastatic pancreatic
      cancer who are fit enough to withstand potential side effects. The best option
      for these patients remains the enrolment in prospective clinical trials.
      Improvements in the treatment of the advanced disease will possibly derive from
      new combinations or from new drugs, but certainly from a better knowledge of the
      multiple molecular pathways implicated in pancreatic carcinogenesis and in
      invasion and metastasis.

PMID- 22458527
TI  - Targeting EGFR in pancreatic cancer treatment.
AB  - The prognosis of patients with pancreatic cancer is extremely poor, and current
      systemic therapies provide marginal survival benefits for treated patients. The
      era of targeted therapies has offered a new avenue to search for potentially more
      effective strategies. Epidermal growth factor receptor (EGFR) is a member of the
      erbB/human epidermal growth factor receptor family of tyrosine kinases, which
      includes erbB2/HER2, erbB3/HER3 and erbB4/HER4. Epidermal growth factor receptor
      overexpression may be detected in up to 90% of pancreatic tumors. Two
      pharmacologic approaches have been successfully used to inhibit epidermal growth
      factor receptor function in cancer treatment: neutralizing monoclonal antibodies
      and small molecule tyrosine inhibitors. The randomized trials studying the
      addition of EGFR targeted agents to gemcitabine compared with gemcitabine alone
      have been disappointing, although results with the EGFR tyrosine kinase inhibitor
      erlotinib were statistically significant but clinically of marginal benefit. In
      this article, we review the epidermal growth factor receptor signaling network in
      pancreatic cancer, the strategies to increase the effectiveness of epidermal
      growth factor receptor inhibitors, and the clinical trials of these inhibitors in
      pancreatic cancer.

PMID- 22458529
TI  - Tyrosine cross-linking reveals interfacial dynamics in adeno-associated viral
      capsids during infection.
AB  - Viral capsid dynamics are often observed during infectious events such as cell
      surface attachment, entry and genome release. Structural analysis of adeno
      associated virus (AAV), a helper-dependent parvovirus, revealed a cluster of
      surface-exposed tyrosine residues at the icosahedral two-fold symmetry axis. We
      exploited the latter observation to carry out selective oxidation of Tyr
      residues, which yielded cross-linked viral protein (VP) subunit dimers,
      effectively "stitching" together the AAV capsid two-fold interface.
      Characterization of different Tyr-to-Phe mutants confirmed that the formation of
      cross-linked VP dimers is mediated by dityrosine adducts and requires the Tyr704
      residue, which crosses over from one neighboring VP subunit to the other. When
      compared to unmodified capsids, Tyr-cross-linked AAV displayed decreased
      transduction efficiency in cell culture. Surprisingly, further biochemical and
      quantitative microscopy studies revealed that restraining the two-fold interface
      hinders externalization of buried VP N-termini, which contain a phospholipase A2
      domain and nuclear localization sequences critical for infection. These adverse
      effects caused by tyrosine oxidation support the notion that interfacial dynamics
      at the AAV capsid two-fold symmetry axis play a role in externalization of VP N
      termini during infection.

PMID- 22458530
TI  - Differential effect of beta-adrenergic receptor antagonism in basolateral
      amygdala on reconsolidation of aversive and appetitive memories associated with
      morphine in rats.
AB  - Positive and negative emotional experiences induced by addictive drugs play an
      important role in the development of dysfunctional drug-related memory, which
      becomes resistant to extinction and contributes to high rate of relapse. Those
      memories may undergo a process called reconsolidation that in some cases can be
      disrupted by pharmacological treatment. The basolateral amygdala (BLA) has been
      shown to mediate the reconsolidation of drug-related appetitive memory, but its
      role in withdrawal-related aversive memory remains elusive. The present study
      used conditioned place preference (CPP) and conditioned place aversion (CPA)
      paradigms to investigate the role of BLA and its noradrenergic receptors in
      reconsolidation of morphine-associated emotional memory in rats. We found that
      inhibition of protein synthesis in BLA disrupted the reconsolidation of morphine
      CPP (m-CPP) and CPA related to morphine withdrawal (m-CPA). A high dose of the
      beta-noradrenergic receptor antagonist propranolol (3 ug) in BLA-impaired
      reconsolidation of m-CPA but not m-CPP, whereas a low dose (0.3 ug) was
      ineffective. In contrast, neither low nor high doses of the alpha-noradrenergic
      receptor antagonist phentolamine (1 or 10 ug) blocked the reconsolidation of m
      CPP and m-CPA. In addition, infusion of propranolol (3 ug) into nucleus accumbens
      after retrieval of either m-CPP or m-CPA did not affect its reconsolidation. The
      findings indicate that appetitive and aversive addictive memories share common
      neural substrates in BLA, but the specific neurotransmitter mechanism on
      reconsolidation of morphine-associated negative and positive memories can be
      dissociable.

PMID- 22458528
TI  - Systemic therapies for pancreatic cancer--the role of pharmacogenetics.
AB  - Effective systemic treatment of pancreatic cancer remains a major challenge, with
      progress hampered by drug resistance and treatment related toxicities. Currently
      available cytotoxic agents as monotherapy or in combination have provided only a
      modest survival benefit for patients with advanced disease. Disappointing phase
      III results with gemcitabine-based combinations in patients with advanced
      pancreatic cancer might be related to poor efficacy of systemic therapies in
      unselected patients. Future research strategies should prioritize identification
      of predictive markers through pharmacogenetic investigations. The
      individualization of patient treatment through pharmacogenetics may help to
      improve outcome by maximizing efficacy whilst lowering toxicity. This review
      provides an update on the pharmacogenetics of pancreatic cancer treatment and its
      influence on treatment benefits and toxicity.

PMID- 22458531
TI  - Discovery of PG545: a highly potent and simultaneous inhibitor of angiogenesis,
      tumor growth, and metastasis.
AB  - Increasing the aglycone lipophilicity of a series of polysulfated oligosaccharide
      glycoside heparan sulfate (HS) mimetics via attachment of a steroid or long chain
      alkyl group resulted in compounds with significantly improved in vitro and ex
      vivo antiangiogenic activity. The compounds potently inhibited heparanase and HS
      binding angiogenic growth factors and displayed improved antitumor and
      antimetastatic activity in vivo compared with the earlier series. Preliminary
      pharmacokinetic analyses also revealed significant increases in half-life
      following iv dosing, ultimately supporting less frequent dosing regimens in
      preclinical tumor models compared with other HS mimetics. The compounds also
      displayed only mild anticoagulant activity, a common side effect usually
      associated with HS mimetics. These efforts led to the identification of 3beta
      cholestanyl 2,3,4,6-tetra-O-sulfo-alpha-d-glucopyranosyl-(1->4)-2,3,6-tri-O-sulfo
      alpha-d-glucopyranosyl-(1->4)-2,3,6-tri-O-sulfo-alpha-d-glucopyranosyl-(1->4)
      2,3,6-tri-O-sulfo-beta-d-glucopyranoside, tridecasodium salt (PG545, 18) as a
      clinical candidate. Compound 18 was recently evaluated in a phase I clinical
      trial in cancer patients.

PMID- 22458534
TI  - Spatially restricted actin-regulatory signaling contributes to synapse
      morphology.
AB  - The actin cytoskeleton in dendritic spines is organized into microdomains, but
      how signaling molecules that regulate actin are spatially governed is
      incompletely understood. Here we examine how the localization of the RacGEF
      kalirin-7, a well-characterized regulator of actin in spines, varies as a
      function of post-synaptic density area and spine volume. Using serial section
      electron microscopy, we find that extrasynaptic, but not synaptic, expression of
      kalirin-7 varies directly with synapse size and spine volume. Moreover, we find
      that overall expression levels of kalirin-7 differ in spines bearing perforated
      and non-perforated synapses, due primarily to extrasynaptic pools of kalirin-7
      expression in the former. Overall, our findings indicate that kalirin-7 is
      differentially compartmentalized in spines as a function of both synapse
      morphology and spine size.

PMID- 22458535
TI  - Knowledge, attitudes and practices related to avian influenza among poultry
      workers in Nepal: a cross sectional study.
AB  - BACKGROUND: Avian influenza is a considerable threat to global public health.
      Prevention and control depend on awareness and protective behaviours of the
      general population as well as high risk-groups. This study aims to explore the
      knowledge, attitudes and practices related to avian influenza among poultry
      workers in Nepal. METHODS: The study was based on a cross-sectional study design,
      using a structured questionnaire administered in face-to-face interviews with 96
      poultry workers age 15 and above from the Rupandehi district in Nepal. RESULTS:
      The majority of respondents were male (80%), mean age was 35 (SD = 11.6). Nearly
      everybody was aware that AI cases had been detected in Nepal and that poultry
      workers were at risk for infection. The major sources of AI information were
      radio, TV and newspapers. Knowledge about preventive measures was high with
      regard to some behaviours (hand washing), but medium to low with regard to others
      (using cleaning and disinfecting procedures or protective clothing). Poultry
      workers who got their information from TV and newspapers and those who were more
      afraid of contracting AI had higher knowledge than those who did not. Being
      employed as compared to being an owner of a poultry farm as well as having a high
      level of knowledge was associated with practising more preventive behaviours.
      While on one hand many specific government control measures found a high degree
      of acceptance, a majority of study participants also thought that government
      control and compensation measures as a whole were insufficient. CONCLUSIONS: The
      study provides information about knowledge and practices regarding avian
      influenza among poultry workers in Nepal. It highlights the importance of
      targeting lack of knowledge as well as structural-material barriers to
      successfully build preparedness for a major outbreak situation.

PMID- 22458536
TI  - Effect of articaine on mental nerve anterior portion: histological analysis in
      rats.
AB  - OBJECTIVES: The aim of this study was to evaluate the possible toxic effects of
      articaine and lidocaine on mental nerve, due to the increasing number of
      paresthesia cases after nerve blocks. MATERIALS AND METHODS: The drugs were
      injected in the anterior portion of mental nerve of 24 rats, divided into three
      groups: G1--4% articaine with 1:100,000 epinephrine; G2--2% lidocaine with
      1:100,000 epinephrine and G3--plain 1:100,000 epinephrine solution. These
      solutions were injected in the right side of the rat's mandible and the left side
      was used as control (0.9% saline solution). Previously to the injections, the
      animals were anesthetized with thiopental and, 24 h after the injections, their
      jaws were removed and submitted to routine histological techniques. A
      histopathological analysis was performed by optical microscopy. RESULTS: An
      inflammatory infiltration was found around mental nerve, classified as intense
      for G3, moderate for G1 and light for both G2 and control groups. No injuries
      were found in nervous structure, despite the inflammatory reaction observed
      around it. CONCLUSION: The results suggest that articaine is not toxic to the
      nervous structure and further studies are necessary to explain the possible
      relation between articaine injection and paresthesia.

PMID- 22458533
TI  - Risk factors and effectiveness of preventive measures against influenza in the
      community.
AB  - BACKGROUND: The role of different risk exposures and preventive measures against
      influenza has not been well established. OBJECTIVE: The aim of this study was to
      evaluate risk factors and measures to prevent influenza infection in the
      community. METHODS: We conducted a multicenter case-control study. Cases were 481
      outpatients aged 18 years or older with laboratory-confirmed influenza A(H1N1)09
      in the 2009-2010 season in Spain. A control was selected for each case from
      outpatients from the same area matched by age and date of consultation.
      Information on risk situations, preventive measures and other variables was
      obtained by interview and review of the medical record. RESULTS: In the
      multivariate conditional logistic regression analysis, the risk of a diagnosis of
      influenza increased with the number of cohabitants (compared with <3 cohabitants,
      three cohabitants had an OR= 1.80, 95% CI 1.12-2.89, and >=5 cohabitants had an
      OR = 2.66, 95% CI 1.31-5.41) and for health care workers (OR = 2.94, 95% CI 1.53
      5.66). The use of metropolitan public transport was associated with a lower
      frequency of a diagnosis of influenza (OR = 0.45, 95% CI 0.30-0.68) but not the
      use of taxis or long-distance transport. The influenza A(H1N1)09 vaccine had a
      protective effect (OR =0.13, 95% CI 0.04-0.48), unlike hand washing after
      touching contaminated surfaces or the use of alcohol-based hand sanitizers.
      CONCLUSION: The home environment appears to play an important role in the spread
      of influenza in adults, but not the use of public transport. Health care workers
      have a higher risk of contracting influenza. Vaccination was the most effective
      preventive measure.

PMID- 22458537
TI  - LARGE enzyme activity deciphered: a new therapeutic target for muscular
      dystrophies.
AB  - A significant proportion of severe, inherited congenital muscular dystrophies are
      due to aberrant glycosylation of the extracellular matrix receptor alpha
      dystroglycan and a consequent lack of ligand-binding activity. A key member of
      this glycosylation pathway is the LARGE protein, which was originally identified
      through genome sequencing and genetic studies. Until recently, the biochemical
      activity of this enzyme proved frustratingly elusive, but a recent study shows
      that LARGE encodes a bifunctional glycosyltransferase that synthesizes a novel
      polysaccharide structure, which is required for functional dystroglycan.
      Identification of this structure should lead to development of new diagnostic
      tools and therapeutic strategies for these dystrophies. 

PMID- 22458538
TI  - Construction of the control system of target molecule expression in Escherichia
      coli: application to a validation platform for bactericidal and bacteriostatic
      profiles due to suppression of a target molecule.
AB  - Validation of bactericidal profiles owing to a deficiency of target bacterial
      molecule provides opportunities to discover antimicrobial drug candidates. In
      this study, we constructed genetic-engineered Escherichia coli strains, in which
      the target gene expression is conditionally regulated by a tryptophan promoter,
      while the target protein expression is regulated by N-end rule-based proteolysis.
      Among 10 genes, whose correspondent proteins are target candidates of antibiotics
      for community acquired respiratory tract infection, it was clearly demonstrated
      that the suppression of DnaB, GlmU, or DnaX results in a bactericidal profile,
      while the suppression of FabB, PyrG, DnaG, Der, PyrH, Era, or IspA leads to a
      bacteriostatic profile. This study is the first to predict the antibacterial
      inhibition profiles of Der, DnaG, DnaX, Era, GlmU, IspA, PyrG, and PyrH, and
      confirms previous findings for DnaB and FabB. The results suggested that the
      system constructed in this study is a novel and useful tool to validate whether
      the target bacterial molecule has appropriate properties as a target of
      antimicrobial agents.

PMID- 22458539
TI  - Three-dimensional structures by two-dimensional vibrational spectroscopy.
AB  - The development of experiments that can generate molecular movies of changing
      chemical structures is a major challenge for physical chemistry. But to realize
      this dream, we not only need to significantly improve existing approaches but
      also must invent new technologies. Most of the known protein structures have been
      determined by X-ray diffraction and to lesser extent by NMR. Though powerful, X
      ray diffraction presents limitations for acquiring time-dependent structures. In
      the case of NMR, ultrafast equilibrium dynamics might be inferred from line
      shapes, but the structures of conformations interconverting on such time scales
      are not realizable.  This Account highlights two-dimensional infrared
      spectroscopy (2D IR), in particular the 2D vibrational echo, as an approach to
      time-resolved structure determination. We outline the use of the 2D IR method to
      completely determine the structure of a protein of the integrin family in a time
      window of few picoseconds. As a transmembrane protein, this class of structures
      has proved particularly challenging for the established structural methodologies
      of X-ray crystallography and NMR.  We describe the challenges facing
      multidimensional spectroscopy and compare it with some other methods of
      structural biology. Then we succinctly discuss the basic principles of 2D IR
      methods as they relate to time domain and frequency domain experimental and
      theoretical properties required for protein structure determination. By means of
      the example of the transmembrane protein, we describe the essential aspects of
      combined carbon-13-oxygen-18 isotope labels to create vibrational resonance pairs
      that allow the determination of protein and peptide structures in motion.
      Finally, we propose a three-dimensional structure of the alphaIIb transmembrane
      homodimer that includes optimum locations of all side chains and backbone atoms
      of the protein.

PMID- 22458540
TI  - Clomiphene citrate is safe and effective for long-term management of
      hypogonadism.
AB  - OBJECTIVE: To assess the efficacy and safety of long-term clomiphene citrate (CC)
      therapy in symptomatic patients with hypogonadism (HG). PATIENTS AND METHODS:
      Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who
      were treated with CC for over 12 months. Additionally, bone densitometry (BD)
      results were collected for all patients. Demographic, comorbidity, treatment and
      Androgen Deficiency in Aging Men (ADAM) score data were also recorded. Comparison
      was made between baseline and post-treatment variables, and multivariable
      analysis was conducted to define predictors of successful response to CC. The
      main outcome measures were predictors of response and long-term results with long
      term CC therapy in hypogonadal patients. RESULTS: The 46 patients (mean age 44
      years) had baseline serum testosterone (T) levels of 228 ng/dL. Follow-up T
      levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years
      (P < 0.001). Mean femoral neck and lumbar spine BD scores improved significantly.
      ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1
      year. No adverse events were reported by any patients. CONCLUSIONS: Clomiphene
      citrate is an effective long-term therapy for HG in appropriate patients. The
      drug raises T levels substantially in addition to improving other manifestations
      of HG such as osteopenia/osteoporosis and ADAM symptoms.

PMID- 22458541
TI  - Lactone metabolite common to the carcinogens dioxane, diethylene glycol, and N
      nitrosomorpholine: aqueous chemistry and failure to mediate liver carcinogenesis
      in the F344 rat.
AB  - 1,4-Dioxan-2-one, 1, was synthesized, and the equilibrium constant between it and
      the hydrolysis product 2-(2-hydroxyethoxy) acetic acid, 2, was determined as K(O)
      = 70 +/- 4 in acidic aqueous media, 25  degrees C, ionic strength 1 M (KCl), and
      5% by volume acetonitrile. The carboxylic acid dissociation constant of 2 was
      determined under the same conditions to be pK(a) = 3.31 +/- 0.02. On the basis of
      these two determinations, the equilibrium constant between 1 and carboxylic acid
      anion, 3, and the proton was calculated to be K(OA) = 0.034 +/- 0.002 M. The
      stability of 1 was determined in the range of pH between 1 and 8.5 in buffered
      aqueous solutions under the conditions above by UV spectrophotometric methods and
      exhibited simple first order kinetics of decay. On the basis of buffer dilution
      plots, the values of k(o), the rate constant for solvent mediated decomposition,
      were determined. The plot of log k(o) against pH is consistent with a three term
      rate law for solvolysis with a hydrogen ion catalyzed rate constant k(H+) = 1.1
      (+/-0.1) M(-1) min(-1), a water catalyzed rate constant, k(w) = 9.9 (+/-0.5) *
      10(-4) min(-1), and a hydroxide ion catalyzed rate constant, k(OH) = 4.1 (+/-0.3)
      * 10(4) M(-1) min(-1). The t(1/2) for decay at pH 7.0, at 25  degrees C, is ~2 h.
      Treatment of F344 rats with aflatoxin B(1) (AFB(1)) (positive control) elicited
      the expected preneoplastic foci in the livers of each rat tested, while
      subsequent administration of 1 (a total of 1.32 g over 12 weeks) failed to
      statistically increase focal number or focal volume percent. In 8 rats
      administered 1 (1.32 g, 12 weeks) alone, no increase above background foci was
      detected. This study does not support compound 1 as a common carcinogen.

PMID- 22458542
TI  - Fluorosugar chain termination agents as probes of the sequence specificity of a
      carbohydrate polymerase.
AB  - Naturally occurring carbohydrate polymers are ubiquitous. They are assembled by
      polymerizing glycosyltransferases, which can generate polysaccharide products
      with repeating sequence patterns. The fidelity of enzymes of this class is
      unknown. We report a method for testing the fidelity of carbohydrate polymerase
      pattern deposition: we synthesized fluorosugar donors and used them as chain
      termination agents. The requisite nucleotide fluorosugars could be produced from
      a single intermediate using the Jacobsen catalyst in a kinetically controlled
      separation of diastereomers. The resulting fluorosugar donors were used by the
      galactofuranosyltransferase GlfT2 from Mycobacterium tuberculosis, and the data
      indicate that this enzyme mediates the cell wall galactan production through a
      sequence-specific polymerization.

PMID- 22458543
TI  - Fungal community dynamics in relation to substrate quality of decaying Norway
      spruce ( Picea abies [L.] Karst.) logs in boreal forests.
AB  - Decaying wood plays an important role in forest biodiversity, nutrient cycling
      and carbon balance. Community structure of wood-inhabiting fungi changes with
      mass loss of wood, but the relationship between substrate quality and decomposers
      is poorly understood. This limits the extent to which these ecosystem services
      can be effectively managed. We studied the fungal community and physico-chemical
      quality (stage of decay, dimensions, density, moisture, C : N ratio, lignin and
      water or ethanol extractives) of 543 Norway spruce logs in five unmanaged boreal
      forest sites of southern Finland. Fungi were identified using denaturing gradient
      gel electrophoresis and sequencing of DNA extracted directly from wood samples.
      Macroscopic fruiting bodies were also recorded. Results showed a fungal community
      succession with decreasing wood density and C : N ratio, and increasing moisture
      and lignin content. Fungal diversity peaked in the most decayed substrates.
      Ascomycetes typically colonized recently fallen wood. Brown-rot fungi preferred
      the intermediate decay stages. White-rot fungi represented approximately one
      fifth of sequenced species in all decay phases excluding the final phase, where
      ectomycorrhizal (ECM) fungi became dominant. Lignin content of logs with white
      rot fungi was low, and ECM fungi were associated with substrates containing
      abundant nitrogen. Macroscopic fruiting bodies were observed for only a small
      number of species detected with molecular techniques.

PMID- 22458544
TI  - Serum brain-derived neurotrophic factor levels were reduced during
      methamphetamine early withdrawal.
AB  - Methamphetamine (METH) abuse is an increasing public health problem worldwide.
      Many of the METH-induced physical and mental problems are associated with the
      neurotoxic effects of METH. Animal studies have shown that brain-derived
      neurotrophic factor (BDNF) decreased after repeated amphetamine administration
      and increased at 30 and 90 days from psychostimulant withdrawal, suggesting that
      there might be a psychostimulant-induced neuroprotective dysfunction followed by
      a neuroadaptive process in the brain. However, current research on the role of
      BDNF in human METH addiction is limited, particularly during early withdrawal.
      The aim of this study was to assess the serum BDNF levels in METH abusers during
      the early withdrawal stage. Two groups of subjects were enrolled: (1) 59 DSM-IV
      METH abusers confirmed by board-certified psychiatrists during the first 3 weeks
      of withdrawal; (2) 59 age- and sex-matched healthy controls. We found that serum
      BDNF levels were significantly and constantly lower in the METH abusers during
      early withdrawal than those of the healthy controls. This indicates that METH
      abusers might have severe BDNF dysfunction and an impaired neuroprotective
      function after repetitive METH misuse. 

PMID- 22458545
TI  - Accidental exposure to UV radiation produced by germicidal lamp: case report and
      risk assessment.
AB  - Ultraviolet radiation is known to cause both benefits and harmful effects on
      humans. The adverse effects mainly involve two target organs, skin and eye, and
      can be further divided into short- and long-term effects. The present case report
      describes an accidental exposure of two health-care workers to ultraviolet
      radiation produced by a germicidal lamp in a hospital pharmacy. The germicidal
      lamp presented a spectrum with an intense UV-C component as well as a modest UV-B
      contribution. Overexposure to UV-C radiation was over 100 times as large as the
      ICNIRP exposure limits. A few hours after the exposure, the two subjects reported
      symptoms of acute UV injury and both of them continued having significant
      clinical signs for over 2 years. In this study, we describe acute and potentially
      irreversible effects caused by high UV exposure. In addition, we present the
      results of risk assessment by occupational exposure to germicidal lamps.

PMID- 22458546
TI  - Constitutive expression of ciliary neurotrophic factor in mouse hypothalamus.
AB  - Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a large
      number of neuronal and glial cells in culture; its expression in glial cells is
      strongly upregulated after a variety of nerve tissue injuries. Exogenously
      administered CNTF produces an anorectic effect via activation of hypothalamic
      neurons and stimulates neurogenesis in mouse hypothalamus. To determine whether
      CNTF is produced endogenously in the hypothalamus, we sought cellular sources and
      examined their distribution in adult mouse hypothalamus by immunohistochemistry.
      CNTF immunoreactivity (IR) was predominantly detected in the ependymal layer
      throughout the rostrocaudal extension of the third ventricle, where numerous
      ependymocytes and tanycytes exhibited specific staining. Some astrocytes in the
      grey matter of the anterior hypothalamus and in the median eminence of the
      hypothalamic tuberal region were also positive. Stimulation of cells bearing CNTF
      receptor alpha (CNTFRalpha) induces specific activation of the signal transducer
      and activator of transcription 3 (STAT3) signalling system. Treatment with
      recombinant CNTF and detection of the nuclear expression of phospho-STAT3 (P
      STAT3) showed that CNTF-producing ependymal cells and tanycytes were intermingled
      with, or very close to, P-STAT3-positive, CNTFRalpha-bearing cells. A fraction of
      CNTF-producing ependymal cells and tanycytes and some median eminence astrocytes
      also exhibited P-STAT3 IR. Thus, in normal adult mice the ependyma of the third
      ventricle is both a source of and a target for CNTF, which may play hitherto
      unknown roles in hypothalamic function in physiological conditions.

PMID- 22458547
TI  - Strategies to minimize CNS toxicity: in vitro high-throughput assays and
      computational modeling.
AB  - INTRODUCTION: Healthy functioning of the brain is dependent on the ability of the
      blood-brain barrier (BBB) and other central nervous system (CNS) barriers to
      protect the neurocompartments from potential disruptive and damaging xenobiotic
      agents. In vitro high-throughput (HT) screens and computational models that
      assess a compound's ability to pass through or disrupt the BBB have become
      important tools in the identification of new well-tolerated peripheral drugs and
      safer chemical products such as pesticides. Leveraging these HT in vitro assays
      and computational BBB tools together with the current understanding of brain
      penetration may enable the drug discovery community to minimize access of drug
      candidates into the CNS compartment. AREAS COVERED: This article reviews aspects
      of the most recent in vitro and computational approaches designed to provide an
      early assessment of a compound's ability to access the neurocompartment. This
      article also provides insight into using these tools to identify compounds that
      have restricted access to the neurocompartment. EXPERT OPINION: The development
      of safer peripheral-acting medicines and chemical products can be achieved
      through prospective design and early assessment with HT assays of the BBB in
      conjunction with computational models. Exclusion or significantly reduced access
      of a compound to the neurocompartment will increase the odds of identifying a
      compound with reduced CNS-related adverse drug reactions. A holistic approach to
      compound design and evaluation that incorporates prospective design principles
      (e.g., optimization of physicochemical properties), leverages HT in vitro assays
      and integrates the use of BBB computational models may yield the 'best-in-class'
      peripherally acting product.

PMID- 22458548
TI  - Mechanisms of hormonal regulation of endosperm cap-specific gene expression in
      tomato seeds.
AB  - The micropylar region of endosperm in a seed, which is adjacent to the radicle
      tip, is called the 'endosperm cap', and is specifically activated before radicle
      emergence. This activation of the endosperm cap is a widespread phenomenon among
      species and is a prerequisite for the completion of germination. To understand
      the mechanisms of endosperm cap-specific gene expression in tomato seeds,
      GeneChip analysis was performed. The major groups of endosperm cap-enriched genes
      were pathogenesis-, cell wall-, and hormone-associated genes. The promoter
      regions of endosperm cap-enriched genes contained DNA motifs recognized by
      ethylene response factors (ERFs). The tomato ERF1 (TERF1) and its experimentally
      verified targets were enriched in the endosperm cap, suggesting an involvement of
      the ethylene response cascade in this process. The known endosperm cap enzyme
      endo-beta-mannanase is induced by gibberellin (GA), which is thought to be the
      major hormone inducing endosperm cap-specific genes. The mechanism of endo-beta
      mannanase induction by GA was also investigated using isolated, embryoless seeds.
      Results suggested that GA might act indirectly on the endosperm cap. We propose
      that endosperm cap activation is caused by the ethylene response of this tissue,
      as a consequence of mechanosensing of the increase in embryonic growth potential
      by GA action.

PMID- 22458549
TI  - Etanercept suppresses regenerative hyperplasia in psoriasis by acutely
      downregulating epidermal expression of interleukin (IL)-19, IL-20 and IL-24.
AB  - BACKGROUND: Psoriasis is a Th17/Th1-mediated skin disease that often responds to
      antitumour necrosis factor (TNF)-alpha therapies, such as etanercept. OBJECTIVES:
      To better define mechanisms by which etanercept improves psoriasis and to gain
      insight into disease pathogenesis. METHODS: We investigated the early biochemical
      and cellular effects of etanercept on skin lesions in responder patients prior to
      substantial clinical improvement (<= 4 weeks). RESULTS: By 1 week, etanercept
      acutely suppressed gene expression of the interleukin (IL)-20 subfamily of
      cytokines (IL-19, IL-20, IL-24), which were found to be predominantly epidermis
      derived and which are implicated in stimulating epidermal hyperplasia.
      Additionally, by 1 week of therapy, suppression of other keratinocyte-derived
      products (chemokines, antimicrobial proteins) occurred, while suppression of
      epidermal regenerative hyperplasia occurred within 1-3 weeks. Th17 elements (IL
      23p19, IL-12p40, IL-17A, IL-22) were suppressed by 3-4 weeks. In vitro, TNF-alpha
      and IL-17A coordinately stimulated the expression of the IL-20 subfamily in
      normal keratinocytes. CONCLUSIONS: Based on the rapid suppression of regenerative
      hyperplasia, chemokines and other keratinocyte-derived products, including the IL
      20 subfamily, we propose that epidermal activation is a very early target of
      etanercept. As many of these keratinocyte markers are stimulated by TNF-alpha,
      their rapid downregulation is likely to reflect etanercept's antagonism of TNF
      alpha. Additionally, decreased epidermal hyperplasia might result specifically
      from acute suppression of the IL-20 subfamily, which is also a likely consequence
      of etanercept's antagonism of TNF-alpha. Thus, the IL-20 subfamily has potential
      importance in the pathogenesis of psoriasis and therapeutic response to
      etanercept.

PMID- 22458550
TI  - Black rice (Oryza sativa L.) extract attenuates hepatic steatosis in C57BL/6 J
      mice fed a high-fat diet via fatty acid oxidation.
AB  - BACKGROUND: Two major risk factors for the onset of fatty liver disease are
      excessive alcohol intake and obesity, the latter being associated with non
      alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the
      effects of black rice extract (BRE) on hepatic steatosis and insulin resistance
      in high-fat diet-fed mice, providing a model of NAFLD. METHODS: Twenty-four mice
      were randomly divided into three groups (n = 8 in each group): normal fat diet
      (ND), high fat diet (HF), and high fat diet supplemented with 1% (w/w) BRE (HF
      +1% BRE). The experimental diets were fed for seven weeks. RESULTS: A HF induced
      hepatic steatosis with significant increases in the serum levels of free fatty
      acids (FFAs), triglyceride (TG), total cholesterol (TC), and insulin. By
      contrast, supplementary BRE (10 g/kg of diet) included in the HF alleviated
      hepatic steatosis and significantly decreased serum TG and TC levels (p < 0.01
      for both). Dietary BRE also increased expression of fatty acid metabolism-related
      genes, including carnitine palmitoyltransferase (CPT1A), acyl-CoA oxidase (ACO),
      cytochrome P450 (CYP4A10), and peroxisome proliferator activated receptor (PPAR)
      alpha (p < 0.05 for all). CONCLUSIONS: Dietary BRE supplementation improved serum
      lipid profiles and significantly enhanced mRNA expression levels of fatty acid
      metabolism-related genes, primarily via beta-oxidation and omega-oxidation in the
      liver. Taken together, these findings suggest that a BRE-supplemented diet could
      be useful in reducing the risks of hepatic steatosis and related disorders,
      including hyperlipidemia and hyperglycemia.

PMID- 22458551
TI  - Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a
      standardized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots
      and Smilax glabra rhizomes with anti- hepatocarcinogenic effects.
AB  - BACKGROUND: A standardized poly-herbal decoction of Nigella sativa seeds,
      Hemidesmus indicus roots and Smilax glabra rhizomes used traditionally in Sri
      Lanka for cancer therapy has been demonstrated previously, to have anti
      hepatocarcinogenic potential. Cytotoxicity, antioxidant activity, anti
      inflammatory activity, and up regulation of p53 and p21 activities are considered
      to be some of the possible mechanisms through which the above decoction may
      mediate its anti-hepatocarcinogenic action. The main aim of the present study was
      to determine whether apoptosis is also a major mechanism by which the decoction
      mediates its anti-hepatocarcinogenic action. METHODS: Evaluation of apoptosis in
      HepG2 cells was carried out by (a) microscopic observations of cell morphology,
      (b) DNA fragmentation analysis, (c) activities of caspase 3 and 9, as well as by
      (d) analysis of the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2)
      proteins associated with cell death. RESULTS: The results demonstrated that in
      HepG2 cells, the decoction can induce (a) DNA fragmentation and (b)
      characteristic morphological changes associated with apoptosis (nuclear
      condensation, membrane blebbing, nuclear fragmentation and apoptotic bodies). The
      decoction could also, in a time and dose dependent manner, up regulate the
      expression of the pro-apoptotic gene Bax and down regulate expression of anti
      apoptotic Bcl-2 gene (as evident from RT-PCR analysis, immunohistochemistry and
      western blotting). Further, the decoction significantly (p < .001) enhanced the
      activities of caspase-3 and caspase-9 in a time and dose dependent manner.
      CONCLUSIONS: Overall findings provide confirmatory evidence to demonstrate that
      the decoction may mediate its reported anti-hepatocarcinogenic effect, at least
      in part, through modulation of apoptosis.

PMID- 22458553
TI  - Photochemistry of tetrasulfur tetranitride: laser flash photolysis and quantum
      chemical study.
AB  - The photochemistry of tetrasulfur tetranitride (1) was studied in hexane solution
      by the laser flash photolysis technique (LFP). The experimental findings were
      interpreted using the results of previous matrix isolation studies (Pritchina,
      E.A.; Gritsan, N.P.; Bally, T.; Zibarev, A.V. Inorg. Chem. 2009, 48, 4075) and
      high-level quantum chemical calculations. LFP produces two primary intermediates,
      one of which is the boat-shaped 8-membered cyclic compound (2) and the other is
      the 6-membered S(3)N(3) cyclic compound carrying an exocyclic (S)-N?S group (3).
      The primary products 2 and 3 absorb a second photon and undergo transformation to
      the 6-membered S(3)N(3) cycle carrying an exocyclic (N)-S=N group (4), which is
      very unstable and converts back to intermediate 3. The quantum yield of the
      primary product formation is close to unity even though the quantum yield of
      photodegradation of 1 is low (~0.01). Thus, 1 is a photochromic compound
      undergoing in solution the thermally reversible photochemical isomerization. The
      mechanism of the photochromic process was established, and the rate constants of
      the elementary reactions were measured.

PMID- 22458552
TI  - CTLA4Ig prevents alloantibody formation following nonhuman primate islet
      transplantation using the CD40-specific antibody 3A8.
AB  - Islet transplantation to treat type 1 diabetes has been limited in part by
      toxicities of current immunosuppression and recipient humoral sensitization.
      Blockade of the CD28/CD80/86 and CD40/CD154 pathways has shown promise to remedy
      both these limitations, but translation has been hampered by difficulties in
      translating CD154-directed therapies. Prior CD40-directed regimens have led to
      prolonged islet survival, but fail to prevent humoral allosensitization. We
      therefore evaluated the addition of CTLA4Ig to a CD40 blockade-based regimen in
      nonhuman primate (NHP) alloislet transplantation. Diabetic rhesus macaques were
      transplanted allogeneic islets using the CD40-specific antibody 3A8, basiliximab
      induction, and sirolimus with or without CTLA4Ig maintenance therapy. Allograft
      survival was determined by fasting blood glucose levels and flow cytometric
      techniques were used to test for donor-specific antibody (DSA) formation. CTLA4Ig
      plus 3A8, basiliximab and sirolimus was well tolerated and induced long-term
      islet allograft survival. The addition of CTLA4Ig prevented DSA formation, but
      did not facilitate withdrawal of the 3A8-based regimen. Thus, CTLA4Ig combines
      with a CD40-specific regimen to prevent DSA formation in NHPs, and offers a
      potentially translatable calcineurin inhibitor-free protocol inclusive of a
      single investigational agent for use in clinical islet transplantation without
      relying upon CD154 blockade.

PMID- 22458554
TI  - Palladium-catalyzed N-acylation of monosubstituted ureas using near
      stoichiometric carbon monoxide.
AB  - The palladium-catalyzed carbonylation of urea derivatives with aryl iodides and
      bromides afforded N-benzoyl ureas (20 examples) in yields attaining quantitative
      via the application of near-stoichiometric amounts of carbon monoxide generated
      from the decarbonylation of the CO precursor, 9-methylfluorene-9-carbonyl
      chloride. The synthetic protocol displayed good functional group tolerance. The
      methodology is also highly suitable for (13)C isotope labeling, which was
      demonstrated through the synthesis of three benzoyl ureas, including the
      insecticide triflumuron, whereby (13)CO was incorporated into the core structure.

PMID- 22458555
TI  - A natural coumarin derivative esculetin offers neuroprotection on cerebral
      ischemia/reperfusion injury in mice.
AB  - Previous studies have demonstrated that a natural coumarin compound esculetin
      (Esc) possesses antioxidant, anti-tumor, and anti-inflammation activities and
      rescues cultured primary neurons from NMDA toxicity. In this study, we
      investigated the neuroprotective effects of Esc on cerebral ischemia/reperfusion
      (I/R) injury in a middle cerebral artery occlusion model in mice. Esc (20 MUg)
      was administered intracerebroventricularly at 30 min before ischemia. We found
      that Esc significantly reduced infarct volume and decreased neurological deficit
      scores after 75 min of ischemia and 24 h of reperfusion. Post-treatment of Esc
      still provided neuroprotection even when Esc was administered after 4 h of
      reperfusion. Our data also indicated that intraperitoneal administration of Esc
      showed protective effects on cerebral I/R injury in a dose-dependent manner. We
      further explored the protective mechanisms of Esc on cerebral I/R injury and
      found that Esc decreased cleaved caspase 3 level, a marker of apoptosis. Finally,
      our data demonstrated that Esc exerted its anti-apoptotic activity by up
      regulating the expression of Bcl-2 and down-regulating the expression of Bax, two
      apoptosis-related proteins. Because of its clinical use as an anticoagulant and
      its safety profile, Esc may have a therapeutic potential for the treatment of
      stroke in the future clinical trials.

PMID- 22458556
TI  - Standardized volumetric 3D-analysis of SPECT/CT imaging in orthopaedics:
      overcoming the limitations of qualitative 2D analysis.
AB  - BACKGROUND: SPECT/CT combines high resolution anatomical 3D computerized
      tomography (CT) and single photon emission computerized tomography (SPECT) as
      functional imaging, which provides 3D information about biological processes into
      a single imaging modality. The clinical utility of SPECT/CT imaging has been
      recognized in a variety of medical fields and most recently in orthopaedics;
      however, clinical adoption has been limited due to shortcomings of analytical
      tools available. Specifically, SPECT analyses are mainly qualitative due to
      variation in overall metabolic uptake among patients. Furthermore, most analyses
      are done in 2D, although rich 3D data are available. Consequently, it is
      difficult to quantitatively compare the position, size, and intensity of SPECT
      uptake regions among patients, and therefore difficult to draw meaningful
      clinical conclusions. METHODS: We propose a method for normalizing orthopaedic
      SPECT/CT data that enables standardised 3D volumetric quantitative measurements
      and comparison among patients. Our method is based on 3D localisation using
      clinically relevant anatomical landmarks and frames of reference, along with
      intensity value normalisation using clinically relevant reference regions. Using
      the normalised data, we describe a thresholding technique to distinguish
      clinically relevant hot spots from background activity. RESULTS: Using an
      exemplar comparison of two patients, we demonstrate how the normalised, 3D
      rendered data can provide a richer source of clinical information and allow
      quantitative comparison of SPECT/CT measurements across patients. Specifically,
      we demonstrate how non-normalized SPECT/CT analysis can lead to different
      clinical conclusions than the normalized SPECT/CT analysis, and that normalized
      quantitative analysis can be a more accurate indicator of pathology. CONCLUSIONS:
      Conventional orthopaedic frames of reference, 3D volumetric data analysis and
      thresholding are used to distinguish clinically relevant hot spots from
      background activity. Our goal is to facilitate a standardised approach to
      quantitative data collection and comparison of clinical studies using SPECT/CT,
      enabling more widespread clinical use of this powerful imaging tool.

PMID- 22458557
TI  - Micro-CT observation of angiogenesis in bone regeneration.
AB  - OBJECTIVES: Restoration of an adequate blood supply is essential for the bone
      healing process and is key to the success of bone augmentation procedures. In
      this study, we evaluated angiogenesis in rat calvarial flat bone defects using in
      vivo microfocus computed tomography (micro-CT). MATERIALS AND METHODS: Twenty
      rats were used. The calvarium was exposed and calvarial bone defects of critical
      (5-mm diameter) and non-critical (2.7-mm diameter) sizes were prepared. Bone
      regeneration and angiogenesis were evaluated by image analysis using micro-CT and
      histological examination. RESULTS: Critical- and non-critical-sized calvarial
      bone defects showed bone regeneration and angiogenesis around the midsagittal
      suture. Critical-sized calvarial bone defects showed approximately 1.2%
      reossification of the original surgical defect, whereas the non-critical-sized
      defects showed approximately 43.3% reossification at day 28. Furthermore,
      angiogenesis was observed later in the critical-sized calvarial bone defects
      (about 38.2%), whereas angiogenesis was observed early in the non-critical-sized
      calvarial bone defects (about 75.5%) at day 28. New blood vessel networks were
      observed around defects of both sizes. CONCLUSIONS: Angiogenesis preceded bone
      regeneration around critical- and non-critical-sized calvarial bone defects.
      Angiogenesis led to full bone formation in non-critical-sized defects.

PMID- 22458558
TI  - Peripapillary retinal nerve fibre thickness profile with optical coherence
      tomography in congenital tilted disc syndrome.

PMID- 22458559
TI  - Design, synthesis, and biological evaluation of conformationally constrained
      analogues of naphthol AS-E as inhibitors of CREB-mediated gene transcription.
AB  - Cyclic AMP response element binding protein (CREB) is often dysregulated in
      cancer cells and is an attractive cancer drug target. Previously, we described
      naphthol AS-E (1) as a small molecule inhibitor of CREB-mediated gene
      transcription. To understand its bioactive conformation, a series of
      conformationally constrained analogues of 1 were designed and synthesized.
      Biological evaluation of these analogues suggests that the global energy minimum
      of 1 is the likely bioactive conformation.

PMID- 22458560
TI  - Analysis of variance: variably complex.

PMID- 22458561
TI  - Brain activation to cocaine cues and motivation/treatment status.
AB  - Motivation to change is believed to be a key factor in therapeutic success in
      substance use disorders; however, the neurobiological mechanisms through which
      motivation to change impacts decreased substance use remain unclear. Existing
      research is conflicting, with some investigations supporting decreased and others
      reporting increased frontal activation to drug cues in individuals seeking
      treatment for substance use disorders. The present study investigated the
      relationship between motivation to change cocaine use and cue-elicited brain
      activity in cocaine-dependent individuals using two conceptualizations of
      'motivation to change': (1) current treatment status (i.e. currently receiving
      versus not receiving outpatient treatment for cocaine dependence) and (2) self
      reported motivation to change substance use, using the Stages of Change Readiness
      and Treatment Eagerness Scale. Thirty-eight cocaine-dependent individuals (14
      currently in treatment) completed a diagnostic assessment and an fMRI cocaine cue
      reactivity task. Whole-brain analyses demonstrated that both treatment-seeking
      and motivated participants had lower activation to cocaine cues in a wide variety
      of brain regions in the frontal, occipital, temporal and cingulate cortices
      relative to non-treatment-seeking and less motivated participants. Future
      research is needed to explain the mechanism by which treatment and/or motivation
      impacts neural cue reactivity, as such work could potentially aid in the
      development of more effective therapeutic techniques for substance-dependent
      patients. 

PMID- 22458563
TI  - Complex formation in aqueous trimethylamine-N-oxide (TMAO) solutions.
AB  - We study aqueous solutions of the amphiphilic osmolyte trimethylamine-N-oxide
      (TMAO) using broadband dielectric spectroscopy and femtosecond mid-infrared
      spectroscopy. Both experiments provide strong evidence for distinctively slower
      rotation dynamics for water molecules interacting with the hydrophobic part of
      the TMAO molecules. Further, water is found to interact more strongly at the
      hydrophilic site of the TMAO molecules: we find evidence for the formation of
      stable, TMAO.2H2O and/or TMAO.3H2O complexes. While this coordination structure
      seems obvious, the lifetime of these complexes is found to be extraordinarily
      long (>50 ps). The existence of these long-lived complexes leads to pronounced
      parallel dipole correlations between water and TMAO, reflected in enhanced
      amplitudes in the dielectric spectra. The strong interaction between water and
      TMAO also results in a red-shifted band for the O-D stretching vibration of HDO
      molecules in an isotopically diluted aqueous TMAO solution. This O-D stretching
      vibration has a vibrational lifetime of 670 fs, which is significantly shorter
      than the lifetime of the O-D stretch vibration of bulk-like HDO molecules,
      presumably due to efficient coupling to vibrational modes of TMAO. The rotational
      dynamics of these O-D groups are slowed down dramatically, and are limited by the
      rotation of the whole complex, while the O-D vector oriented away from TMAO
      probably shows an accelerated reorientation. 

PMID- 22458564
TI  - Distinguishing between erythema multiforme major and Stevens-Johnson
      syndrome/toxic epidermal necrolysis immunopathologically.
AB  - The early clinical presentations of Stevens-Johnson syndrome (SJS) and toxic
      epidermal necrolysis (TEN) are similar to that of erythema multiforme major
      (EMM). Cytotoxic molecules, especially granulysin, are expressed in the skin
      lesions of SJS/TEN and cause extensive keratinocyte death. It is postulated that
      the function of regulatory T cells (Treg) in SJS/TEN is inadequate. This study
      examined whether an immunohistological examination of cytotoxic molecules and the
      immunophenotype of Treg is useful for discriminating SJS from EMM in the early
      period. Over the past 9 years, the lesional skin of 14 patients with SJS/TEN and
      16 patients with EMM was biopsied. Double immunofluorescence labeling of CD8 and
      granulysin, perforin, or granzyme B was performed, and immunohistochemical
      analyses of granulysin, perforin, granzyme B, CD1a, CD3, CD4, CD8, CD68 and Foxp3
      were conducted using a highly sensitive indirect immunoperoxidase technique. The
      number of cells positive for each antibody per five high-power fields was
      counted. The proportions of granulysin(+) cells/CD8(+) cells (P = 0.012) and
      perforin(+) cells/CD8(+) cells (P = 0.037) in SJS/TEN were significantly higher
      than in EMM. The number of Foxp3(+) cells/five high-power fields in SJS/TEN was
      significantly lower than in EMM (P = 0.004). Similarly, the number of CD4(+)
      cells/five high-power fields in SJS/TEN was significantly lower than in EMM (P =
      0.0017). These data suggest that these panels of antibodies for labeling
      cytotoxic molecules, CD4 and Treg are useful for discriminating early SJS/TEN and
      EMM with a skin biopsy.

PMID- 22458565
TI  - Human parvovirus PARV4 in plasma pools of Chinese origin.
AB  - Human parvovirus 4 (PARV4) is present in blood and blood products. As the
      presence and levels of PARV4 in Chinese source plasma pools have never been
      determined, we implemented real-time quantitative PCR to investigate the presence
      of PARV4 in source plasma pools in China. Results showed that 26.15% (51/195) of
      lots tested positive for PARV4. The amounts of DNA ranged from 2.83 * 10(3)
      copies/ml to 2.35*10(7) copies/ml plasma. The high level of PARV4 in plasma pools
      may pose a potential risk to recipients. Further studies on the pathogenesis of
      PARV4 are urgently required.

PMID- 22458567
TI  - Metal-free tandem Friedel-Crafts/lactonization reaction to benzofuranones bearing
      a quaternary center at C3 position.
AB  - A metal-free tandem Friedel-Crafts/lactonization reaction to 3,3-diaryl or 3
      alkyl-3-aryl benzofuranones catalyzed by HClO(4) was reported. A variety of
      tertiary alpha-hydroxy acid esters could readily react with substituted phenols
      to afford the desired products in rich diversity. The synthetic utility of the
      products was demonstrated by the synthesis of polycyclic compounds. (1)H NMR
      studies supported that this tandem reaction proceeded via tandem Friedel
      Crafts/lactonization sequence.

PMID- 22458566
TI  - Next-generation community genetics for low- and middle-income countries.
AB  - A recent report by the World Health Organization calls for implementation of
      community genetics programs in low- and middle-income countries (LMICs). Their
      focus is prevention of congenital disorders and genetic diseases at the
      population level, in addition to providing genetics services, including diagnosis
      and counseling. The proposed strategies include both newborn screening and
      population screening for carrier detection, in addition to lowering the incidence
      of congenital disorders and genetic diseases through the removal of environmental
      factors. In this article, we consider the potential impact of such testing on
      global health and highlight the near-term relevance of next-generation sequencing
      (NGS) and bioinformatic approaches to their implementation. Key attributes of NGS
      for community genetics programs are homogeneous approach, high multiplexing of
      diseases and samples, as well as rapidly falling costs of new technologies. In
      the near future, we estimate that appropriate use of population-specific test
      panels could cost as little as $10 for 10 Mendelian disorders and could have a
      major impact on diseases that currently affect 2% of children worldwide. However,
      the successful deployment of this technological innovation in LMICs will require
      high value for human life, thoughtful implementation, and autonomy of individual
      decisions, supported by appropriate genetic counseling and community education. 

PMID- 22458568
TI  - Structure-guided design, synthesis, and evaluation of guanine-derived inhibitors
      of the eIF4E mRNA-cap interaction.
AB  - The eukaryotic initiation factor 4E (eIF4E) plays a central role in the
      initiation of gene translation and subsequent protein synthesis by binding the 5'
      terminal mRNA cap structure. We designed and synthesized a series of novel
      compounds that display potent binding affinity against eIF4E despite their lack
      of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The
      biochemical activity of compound 33 is 95 nM for eIF4E in an SPA binding assay.
      More importantly, the compound has an IC(50) of 2.5 MUM for inhibiting cap
      dependent mRNA translation in a rabbit reticular cell extract assay (RRL-IVT).
      This series of potent, truncated analogues could serve as a promising new
      starting point toward the design of neutral eIF4E inhibitors with physicochemical
      properties suitable for cellular activity assessment.

PMID- 22458569
TI  - Modeling the crystallization of spherical nucleic acid nanoparticle conjugates
      with molecular dynamics simulations.
AB  - We use molecular dynamics simulations to study the crystallization of spherical
      nucleic-acid (SNA) gold nanoparticle conjugates, guided by sequence-specific DNA
      hybridization events. Binary mixtures of SNA gold nanoparticle conjugates
      (inorganic core diameter in the 8-15 nm range) are shown to assemble into BCC,
      CsCl, AlB(2), and Cr(3)Si crystalline structures, depending upon particle
      stoichiometry, number of immobilized strands of DNA per particle, DNA sequence
      length, and hydrodynamic size ratio of the conjugates involved in
      crystallization. These data have been used to construct phase diagrams that are
      in excellent agreement with experimental data from wet-laboratory studies.

PMID- 22458571
TI  - Lipoprotein oxidation biomarkers for cardiovascular risk: what does the future
      hold?

PMID- 22458570
TI  - Functional effects of the TMEM43 Ser358Leu mutation in the pathogenesis of
      arrhythmogenic right ventricular cardiomyopathy.
AB  - BACKGROUND: The Ser358Leu mutation in TMEM43, encoding an inner nuclear membrane
      protein, has been implicated in arrhythmogenic right ventricular cardiomyopathy
      (ARVC). The pathogenetic mechanisms of this mutation are poorly understood.
      METHODS: To determine the frequency of TMEM43 mutations as a cause of ARVC, we
      screened 11 ARVC families for mutations in TMEM43 and five desmosomal genes
      previously implicated in the disease. Functional studies were performed in COS-7
      cells transfected with wildtype, mutant, and 1:2 wildtype:mutant TMEM43 to
      determine the effect of the Ser358Leu mutation on the stability and cellular
      localization of TMEM43 and other nuclear envelope and desmosomal proteins,
      assessed by solubility assays and immunofluorescence imaging. mRNA expression was
      assessed of genes potentially affected by dysfunction of the nuclear lamina.
      RESULTS: Three novel mutations in previously documented desmosomal genes, but no
      mutations in TMEM43, were identified. COS-7 cells transfected with mutant TMEM43
      exhibited no change in desmosomal stability. Stability and nuclear membrane
      localization of mutant TMEM43 and of lamin B and emerin were normal. Mutant
      TMEM43 did not alter the expression of genes located on chromosome 13, previously
      implicated in nuclear envelope protein mutations leading to skeletal muscular
      dystrophies. CONCLUSIONS: Mutant TMEM43 exhibits normal cellular localization and
      does not disrupt integrity and localization of other nuclear envelope and
      desmosomal proteins. The pathogenetic role of TMEM43 mutations in ARVC remains
      uncertain.

PMID- 22458572
TI  - Should statins be included in standard care following ischemic stroke in young
      people?

PMID- 22458574
TI  - Bivalirudin for primary percutaneous coronary intervention in acute myocardial
      infarction: the HORIZONS-AMI trial.
AB  - The combination of unfractionated heparin (UFH) plus glycoprotein IIb/IIIa
      inhibitors (GPIs) has been a frequently used anti-thrombotic treatment strategy
      for acute coronary syndrome patients, including those with ST-segment elevation
      myocardial infarction undergoing primary percutaneous coronary intervention.
      However, the ischemic benefit of the UFH plus GPI combination came at the expense
      of high rates of bleeding complications and thrombocytopenia, both of which have
      been independently associated with increased mortality. By contrast, bivalirudin
      monotherapy compared with the combination of UFH plus GPI resulted in improved
      net clinical outcomes, based on similar ischemic protection with significant
      reductions in bleeding complications in randomized trials including patients with
      stable angina, those with unstable angina and those with non-ST-segment elevation
      myocardial infarction. More recently, the HORIZONS-AMI randomized, open-label,
      multicenter trial has compared the efficacy and safety of bivalirudin alone
      versus UFH plus a GPI in 3602 patients with ST-segment elevation myocardial
      infarction undergoing primary percutaneous coronary intervention. Clinical
      results derived from this large study, including the final 3-year follow-up data,
      will be reviewed in the present clinical trial report.

PMID- 22458575
TI  - Thromboembolic prophylaxis in orthopedic surgery using dabigatran: an oral direct
      thrombin inhibitor.
AB  - Dabigatran etexilate is a direct thrombin inhibitor that has been in clinical use
      for the prevention and treatment of venous and arterial thrombosis. Dabigatran
      allows for oral administration, has a rapid onset of action and has a predictable
      anticoagulant effect. Studies in healthy volunteers and in patients undergoing
      orthopedic surgery indicate that dabigatran has a predictable pharmacokinetic
      profile, allowing for a fixed-dose regimen without the need for coagulation
      monitoring. Dabigatran is approved in the EU and Canada for prophylaxis of
      thromboembolism in patients undergoing total hip and knee arthroplasties. The
      focus of this article is on the clinical data of using dabigatran as venous
      thromboprophylaxis in orthopedic surgery patients.

PMID- 22458576
TI  - No country for old stents? Improving long-term patient outcomes with
      biodegradable polymer drug-eluting stents.
AB  - Biodegradable polymer-coated drug-eluting stents (DESs) represent an attractive
      approach to improve vascular healing after coronary intervention. The proof-of
      concept chain of investigation includes preclinical safety assessment, surrogate
      end point clinical efficacy studies and large-scale clinical outcome studies, in
      which noninferiority against benchmark devices is assessed at 12 months, with
      adjudication of hypothesized clinical advantage at long-term follow-up. The 4
      year outcome data from large-scale trials such as the LEADERS study represents a
      final link in this process. Data from this trial show maintenance of
      noninferiority and an overall improvement in the composite of death, myocardial
      infarction and revascularization with biodegradable polymer DESs versus durable
      polymer sirolimus-eluting stents that is statistically significant and perhaps
      also clinically important (risk ratio: 0.81; 95% CI: 0.66-1.00; p-value for
      superiority = 0.05). Furthermore, although reductions in the incidence of stent
      thrombosis with biodegradable polymer stents at 4 years did not reach statistical
      significance, in keeping with the hypothesized mechanism of benefit, the observed
      risk differences seemed to be driven by a reduction in very late events beyond 1
      year after intervention. These findings are backed up by those from a pooled
      analysis of the three largest biodegradable polymer DES randomized trials. With
      the availability of high-quality biodegradable polymer devices and the phasing
      out of earlier generation devices, the next 5 years will see increasing uptake of
      this therapy in routine practice. Whether improvements in outcomes with
      biodegradable polymer DESs can also be demonstrated against second-generation
      durable polymer stents is the subject of a number of ongoing clinical trials.

PMID- 22458577
TI  - Aspirin in stroke prevention in nonvalvular atrial fibrillation and stable
      vascular disease: an era of new anticoagulants.
AB  - Atrial fibrillation (AF) is a major cause of ischemic stroke, especially in the
      elderly. There are currently enough data to support the notion that
      anticoagulation with warfarin or dabigatran is far superior to aspirin in the
      prevention of stroke or systemic embolism in AF. Aspirin is the preferred
      modality in patients who are either not candidates for anticoagulation, such as
      patients with increased risk for bleeding, low-risk patients based on the CHADS2
      score or patients who have difficulty in maintaining a therapeutic international
      normalized ratio. There is no dispute on the recommendations regarding stroke
      prevention in high-risk patients (CHADS2 risk score of 2 and beyond) with AF.
      However, there is some controversy regarding the appropriate strategy
      (anticoagulation vs aspirin) for stroke prevention in low-risk patients (CHA2DS2
      VASc score of 0-1). Novel oral anticoagulant drugs (direct thrombin inhibitors
      and Factor Xa inhibitors) might further diminish the role of aspirin for stroke
      prevention in AF due to their superior efficacy, lack of need for monitoring of
      therapeutic effects and lower bleeding risk when compared with warfarin,
      especially in patients with stable vascular disease.

PMID- 22458578
TI  - New technologies aimed at percutaneous intervention in the small coronary artery.
AB  - Percutaneous coronary intervention (PCI) of small vessels can be complicated by
      technically difficult access to the target lesion, an increased risk of major
      adverse cardiac events and in-stent restenosis requiring repeat
      revascularization. Conventional management of such lesions is with drug-eluting
      stent implantation; however, these have only partly attenuated the problem. In
      response, several medical device companies are competing to produce new
      technologies aimed at PCI in small coronary arteries. Such innovations include
      thin-strutted stents, stent-on-a-wire systems, drug-coated balloons, endothelial
      progenitor cell-catching stents and biodegradable stent systems. To date, none of
      these techniques have been sufficiently validated for use in small coronary
      arteries to justify a change in practice; however, small-vessel coronary artery
      disease is an increasingly common problem, and PCI of target lesions with
      reference vessel diameter <3.0 mm is likely to increase, especially in view of
      the increasing prevalence of diabetes, warranting further well-designed studies.
      The prospect of mounting a self-expandable biodegradable drug-eluting stent
      directly onto a guidewire could potentially be an exciting future development.

PMID- 22458579
TI  - Current imaging modalities for atherosclerosis.
AB  - Atherosclerotic disease is responsible for nearly half of all deaths in the
      western world. During the past three decades, considerable efforts have been made
      towards detection and assessment of atherosclerosis plaques in various vascular
      beds using different imaging techniques. Recently, both noninvasive and invasive
      modalities have frequently been used to refine cardiovascular risk assessment in
      high-risk individuals, to evaluate the natural history of atheroma burden and to
      reveal the impact of anti-atherosclerotic medical therapies on disease
      progression. In this review, we provide an overview of the currently available
      imaging modalities. This article will underscore arterial wall imaging to assess
      the impact of medical therapies on atherosclerosis and to develop the effective
      therapeutic strategies, resulting in the prevention of cardiovascular
      complications.

PMID- 22458580
TI  - Novel drugs for oral anticoagulation pharmacotherapy.
AB  - Long-term anticoagulation with warfarin is the mainstay of treatment in patients
      with diseases with high thromboembolic potential, such as atrial fibrillation.
      However, warfarin therapy carries a number of inherent limitations, including
      slow onset and offset of action, interindividual variability, food and drug
      interactions, lack of selectivity and a narrow therapeutic window. Recently
      developed oral anticoagulants that selectively block key factors in the
      coagulation cascade, with no need for monitoring or dose adjustment, have the
      potential to replace warfarin in clinical practice. The safety and efficacy of
      these agents in patients with atrial fibrillation, venous thromboembolisms and
      acute coronary syndromes have been the object of numerous recent large-scale
      clinical investigations. This article provides an overview of the evidence
      currently available on the use of novel, orally available, selective
      anticoagulants in patients at risk for thromboembolic events.

PMID- 22458581
TI  - Acute coronary syndromes: considerations for improved acceptance and
      implementation of management guidelines.
AB  - The management of acute coronary syndrome in Europe is covered by various
      European Society of Cardiology guidelines, which although valuable, are complex
      and may not always provide clear guidance in everyday clinical practice.
      Consequently, implementation of the guideline recommendations is frequently
      suboptimal. To complicate matters further, a wealth of new data from large trials
      examining novel anti-thrombotic agents will become or are already available,
      necessitating guideline updates. This article summarizes the gaps between current
      guideline-recommended treatment of acute coronary syndrome and daily practice as
      dictated by the evidence base, including recent trials. Reasons for the
      suboptimal implementation of the current European Society of Cardiology
      guidelines and possible solutions to making these more practice oriented are
      presented.

PMID- 22458582
TI  - Diagnosis and treatment of severe hypertriglyceridemia.
AB  - Severe hypertriglyceridemia is associated with acute pancreatitis and can be a
      manifestation of lipoprotein lipase (LPL) deficiency. It is associated with a
      spectrum of disorders, ranging from heterozygous LPL deficiency allied with
      environmental factors to rare severe cases of homozygous LPL deficiency. The
      genes associated with reduced LPL activity include LPL, its cofactor apoC-2, a
      controlling protein apoA-5 and the LPL receptor GPI-HBP1. The effects of
      mutations are exacerbated by environmental factors such as diet, pregnancy and
      insulin resistance. Treatment of clinical LPL deficiency is by ultra-low-fat diet
      along with the use of fibrates, omega-3 fatty acids, niacin, statins and insulin
      sensitizing therapies, depending on the extent of residual LPL activity. Novel
      therapies that target lipoprotein particle assembly through the antisense
      oligonucleotides or by interference with triglyceride-loading microsomal
      transport protein inhibitors offer new potential options for treating
      hypertriglyceridemia.

PMID- 22458583
TI  - Advanced neuroimaging in stroke patients: prediction of tissue fate and
      hemorrhagic transformation.
AB  - Stroke is the second greatest cause of mortality worldwide after ischemic heart
      disease. It is also the leading cause of disability in industrialized countries.
      According to the WHO, 15 million people worldwide suffer a stroke annually. It is
      very difficult to distinguish between an ischemic and a hemorrhagic stroke on a
      clinical basis, therefore imaging (computed tomography or MRI) plays a central
      role in the evaluation of patients with acute stroke symptoms. Because of
      significant advances over the last decade, imaging now provides information
      beyond the mere presence or absence of intracerebral hemorrhage. Comprehensive
      neurovascular imaging protocols using computed tomography or MRI can be acquired
      within minutes, helping to distinguish stroke etiology and guiding treatment
      decisions for acute reperfusion therapies. The purpose of this article is to give
      an overview of diagnostic information provided by neuroimaging in the setting of
      acute stroke, especially ischemic stroke, including information about brain
      tissue viability status and blood-brain barrier permeability. We will discuss the
      indications of the current treatment options for stroke, and how imaging
      influences treatment decision. We will organize our discussion around the concept
      of the 'four Ps' (parenchyma, pipes, penumbra and permeability) proposed by
      Howard Rowley, which is an excellent guide for understanding the underlying
      causes and pathophysiology of ischemic stroke.

PMID- 22458584
TI  - Obstructive sleep apnea and stroke.
AB  - Obstructive sleep apnea (OSA) is a common disorder that has been associated with
      many cardiovascular disease processes, including hypertension and arrhythmias.
      OSA has also been identified as an independent risk factor for stroke and all
      cause mortality. OSA is highly prevalent in patients with transient ischemic
      attacks and stroke. Routinely screening patients with transient ischemic attacks
      or stroke for sleep apnea is becoming more common. In stroke patients with OSA,
      treatment with continuous positive airway pressure may prevent subsequent
      cardiovascular events and improve neurologic outcomes. This review explores the
      pathophysiology of the association between OSA and stroke, and the clinical
      implications of identification and treatment of OSA in patients with stroke.

PMID- 22458586
TI  - Alternative immunomodulatory strategies for xenotransplantation: CD40/154 pathway
      sparing regimens promote xenograft survival.
AB  - Immunosuppressive therapies that block the CD40/CD154 costimulatory pathway have
      proven to be uniquely effective in preclinical xenotransplant models. Given the
      challenges facing clinical translation of CD40/CD154 pathway blockade, we
      examined the efficacy and tolerability of CD40/CD154 pathway-sparing
      immunomodulatory strategies in a pig-to-nonhuman primate islet xenotransplant
      model. Rhesus macaques were rendered diabetic with streptozocin and given an
      intraportal infusion of ~ 50 000 islet equivalents/kg wild-type neonatal porcine
      islets. Base immunosuppression for all recipients included maintenance therapy
      with belatacept and mycophenolate mofetil plus induction with basiliximab and LFA
      1 blockade. Cohort 1 recipients (n = 3) were treated with the base regimen alone;
      cohort 2 recipients (n = 5) were additionally treated with tacrolimus induction
      and cohort 3 recipients (n = 5) were treated with alefacept in place of
      basiliximab, and more intense LFA-1 blockade. Three of five recipients in both
      cohorts 2 and 3 achieved sustained insulin-independent normoglycemia (median
      rejection-free survivals 60 and 111 days, respectively), compared to zero of
      three recipients in cohort 1. These data show that CD40/CD154 pathway-sparing
      regimens can promote xenoislet survival. Further optimization of these strategies
      is warranted to aid the clinical translation of islet xenotransplantation.

PMID- 22458588
TI  - A novel mutation in the PLCD1 gene, which leads to an aberrant splicing event,
      underlies autosomal recessive leuconychia.

PMID- 22458589
TI  - Early bone resorption after vertical bone augmentation--a comparison of calvarial
      and iliac grafts.
AB  - OBJECTIVE AND AIM: Severe cases of bone atrophy in the maxilla or mandible are
      often reconstructed using bone from extraoral donor sides. Most commonly, grafts
      from the iliac crest are used for augmentation, however, frequently associated
      with bone resorption as possible late complication. Calvarial bone grafts, often
      reported to show less resorption, are an alternative. The aim of this study was
      to compare the bone stability of vertical bone grafts from the iliac crest and
      the calvarium. PATIENTS AND METHODS: Twenty-three patients receiving vertical
      onlay bone grafts were included in this retrospective cohort study. In nine
      patients alveolar ridge defects were treated with bone from the iliac crest.
      Fourteen patients were reconstructed using calvarial bone grafts. To quantify
      bone resorption, the data of digital panographs were evaluated. Radiographs were
      taken prior to bone grafting, after augmentation surgery, 6 months after bone
      healing, prior to implant surgery, after implant surgery and at yearly intervals
      thereafter. RESULTS: Postoperative complications at the recipient site occurred
      equally in both groups. The complication rate was 35.7% for the calvarial group
      and 33.3% in the iliac crest group. No donor-site complications were reported in
      either group. After bone augmentation procedure, a mean vertical bone gain of
      8.55 mm (SD 5.96) was measured. Bone grafts from the iliac crest showed a
      significantly higher bone loss of 24.16% (SD 8.47) than grafts from the calvarium
      (8.44%, SD 3.64) at the time of implant placement (P = 0.0003). Implant survival
      was similar in both groups. DISCUSSION: Both bone-grafting approaches are
      successful and reliable techniques, enabling implant placement in even highly
      atrophied alveolar ridges and with identical implant survival rates, although
      bone resorption differs. Within the limitations of this study bone from the
      calvarium shows higher bone stability in the early healing phase.

PMID- 22458587
TI  - Warmth suppresses and desensitizes damage-sensing ion channel TRPA1.
AB  - BACKGROUND: Acute or chronic tissue damage induces an inflammatory response
      accompanied by pain and alterations in local tissue temperature. Recent studies
      revealed that the transient receptor potential A1 (TRPA1) channel is activated by
      a wide variety of substances that are released following tissue damage to evoke
      nociception and neurogenic inflammation. Although the effects of a noxious range
      of cold temperatures on TRPA1 have been rigorously studied, it is not known how
      agonist-induced activation of TRPA1 is regulated by temperature over an innocuous
      range centred on the normal skin surface temperature. This study investigated the
      effect of temperature on agonist-induced currents in human embryonic kidney (HEK)
      293 cells transfected with rat or human TRPA1 and in rat sensory neurons.
      RESULTS: Agonist-induced TRPA1 currents in HEK293 cells were strongly suppressed
      by warm temperatures, and almost abolished at 39 degrees C. Such inhibition
      occurred when TRPA1 was activated by either electrophilic or non-electrophilic
      agonists. Warming not only decreased the apparent affinity of TRPA1 for mustard
      oil (MO), but also greatly enhanced the desensitization and tachyphylaxis of
      TRPA1. Warming also attenuated MO-induced ionic currents in sensory neurons.
      These results suggest that the extent of agonist-induced activity of TRPA1 may
      depend on surrounding tissue temperature, and local hyperthermia during acute
      inflammation could be an endogenous negative regulatory mechanism to attenuate
      persistent pain at the site of injury. CONCLUSION: These results indicate that
      warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Such warmth
      induced suppression of TRPA1 may also explain, at least in part, the mechanistic
      basis of heat therapy that has been widely used as a supplemental anti
      nociceptive approach.

PMID- 22458590
TI  - Housing and dustbathing effects on northern fowl mites (Ornithonyssus sylviarum)
      and chicken body lice (Menacanthus stramineus) on hens.
AB  - Hen housing (cage or cage-free) did not impact overall abundances of northern
      fowl mites, Ornithonyssus sylviarum (Canestrini & Fanzago) (Acari:
      Macronyssidae), or chicken body lice, Menacanthus stramineus (Nitzsch)
      (Phthiraptera: Menoponidae). Cage-free hens received a dustbox with sand plus
      diatomaceous earth (DE), kaolin clay or sulphur. Weekly use varied from none to
      100% of hens; 73% of hens used the dustbox at least once. Ectoparasite
      populations on dustbathing hens (users) were compared with those on non-user cage
      free and caged hens. All materials reduced ectoparasites on user hens by 80-100%
      after 1 week of dustbox use. Diatomaceous earth and kaolin failed to reduce
      ectoparasites on non-user hens, and ectoparasites on user hens recovered after
      dustbox removal. A sulphur dustbox eliminated mites from all hens (including non
      users) within 2-4 weeks. Residual sulphur controlled mites until the end of the
      experiment (up to 9 weeks), even after the dustbox was removed. Louse populations
      on hens using the sulphur dustbox were reduced in 1-2 weeks. Residual sulphur
      effects were less evident in lice, but the use of a sulphur dustbox by a higher
      proportion of hens extended louse control to all hens. This is the first
      experimental study to show that bird dustbathing in naturally and widely
      available dust materials (particularly kaolin) can suppress ectoparasites and
      thus the behaviour is probably adaptive.

PMID- 22458591
TI  - Proinflammatory activities of leptin in non-autoimmune conditions.
AB  - Leptin is an adipokine whose proinflammatory properties contribute to the
      pathogenesis of several autoimmune diseases but also to the development and
      progression of inflammation in several non-autoimmune inflammatory conditions of
      the kidney, liver, lung, endometrium, blood vessels and endothelia. Here we
      review the influences of leptin in those conditions and the pertinent
      experimental work that has defined some mechanisms of action and/or suggested a
      therapeutic potential for leptin-based modulation of inflammation in non
      autoimmune conditions.

PMID- 22458592
TI  - Bilateral cataract induced by unilateral UVR-B exposure -- evidence for an
      inflammatory response.
AB  - PURPOSE: To investigate whether unilateral in vivo UVR-B exposure of one eye
      affects the fellow eye in a co-cataractogenic, sympathetic reaction and to
      determine whether an inflammatory response could be involved in the pathogenesis.
      METHODS: C57BL/6 mice were unilaterally exposed in vivo to UVR-B for 15 min. In
      the group of 24 animals each received 0*/2*/3*/or 4* cataract threshold
      equivalent dose. Following 48-hr UVR-B exposure, cataract morphology was
      documented in dark-field illumination photography, and light scattering was
      quantified, in both lenses in vitro. Serum levels of pro-inflammatory cytokines
      IL-1beta, IL-6 and TNF-alpha were analysed with ELISA. Immunohistochemistry was
      performed for inflammatory infiltration in exposed and contralateral eyes.
      RESULTS: UVR-B exposure induced cataract in all exposed lenses. There was
      additionally a significant UVR dose-dependent increase in light scattering in the
      lenses of the non-exposed fellow eye. Inflammatory infiltration was detected
      immunohistochemically in the anterior segment of both eyes. IL-1beta serum
      concentration increased with increasing UVR-B exposure dose. There was a similar
      trend for serum IL-6 but not for TNF-alpha. CONCLUSION: Unilateral UVR-B exposure
      to one eye is associated with intraocular inflammation and an increase in lens
      light scattering also in the unexposed, fellow eye. A resulting systemic
      inflammatory response might be mediated by IL-1beta and possibly IL-6. The
      finding that an inflammatory response may play a role in UVR-B-induced cataract
      development might initiate new strategies in the prevention of the disease.

PMID- 22458593
TI  - Mild-temperature Mn2(CO)10-photomediated controlled radical polymerization of
      vinylidene fluoride and synthesis of well-defined poly(vinylidene fluoride) block
      copolymers.
AB  - By contrast to typical high-temperature (100-250  degrees C) telo
      /polymerizations of gaseous fluorinated monomers, carried out in high-pressure
      metal reactors, the visible light, Mn(2)(CO)(10)-photomediated initiation of
      vinylidene fluoride (bp = -83  degrees C) polymerization occurs readily from a
      variety of alkyl, semifluorinated, and perfluorinated halides at 40  degrees C,
      in low-pressure glass tubes and in a variety of solvents, including water and
      alkyl carbonates. Perfluorinated alkyl iodide initiators also induce a controlled
      radical polymerization via iodine degenerative transfer (IDT). While IDT proceeds
      with accumulation of the less reactive P(m)-CF(2)-CH(2)-I vs the P(n)-CH(2)-CF(2)
      I chain ends, Mn(2)(CO)(10) enables their subsequent quantitative activation
      toward the synthesis of well-defined poly(vinylidene fluoride) block copolymers
      with a variety of other monomers.

PMID- 22458594
TI  - Ni, Pd, Pt, and Ru complexes of phosphine-borate ligands.
AB  - The species Cy(2)PHC(6)F(4)BF(C(6)F(5))(2) reacts with Pt(PPh(3))(4) to yield the
      new product cis-(PPh(3))(2)PtH(Cy(2)PC(6)F(4)BF(C(6)F(5))(2)) 1 via oxidative
      addition of the P-H bond of the phosphonium borate to Pt(0). The corresponding
      reaction with Pd(PPh(3))(4) affords the Pd analogue of 1, namely, cis
      (PPh(3))(2)PdH(Cy(2)PC(6)F(4)BF(C(6)F(5))(2)) 3; while modification of the
      phosphonium borate gave the salt
      [(PPh(3))(3)PtH][(tBu(2)PC(6)F(4)BF(C(6)F(5))(2))] 2. Alternatively initial
      deprotonation of the phosphonium borate gave
      [tBu(3)PH][Cy(2)PC(6)F(4)BF(C(6)F(5))(2)] 4,
      [SIMesH][Cy(2)PC(6)F(4)BF(C(6)F(5))(2)] 5 which reacted with NiCl(2)(DME)
      yielding [BaseH](2)[trans-Cl(2)Ni(Cy(2)PC(6)F(4)BF(C(6)F(5))(2))(2)] (Base =
      tBu(3)P 6, SIMes 7) or with PdCl(2)(PhCN)(2) to give [BaseH](2)[trans
      Cl(2)Pd(Cy(2)PC(6)F(4)BF(C(6)F(5))(2))(2)] (Base = tBu(3)P 8, SIMes 9). While
      [C(10)H(6)N(2)(Me)(4)H][tBu(2)PC(6)F(4)BF(C(6)F(5))(2)] 10 was also prepared. A
      third strategy for formation of a metal complex of anionic phosphine-borate
      derivatives was demonstrated in the reaction of (COD)PtMe(2) with the neutral
      phosphine-borane Mes(2)PC(6)F(4)B(C(6)F(5))(2) affording
      (COD)PtMe(Mes(2)PC(6)F(4)BMe(C(6)F(5))(2)) 11. Extension of this reactivity to
      tBu(2)PH(CH(2))(4)OB(C(6)F(5))(3)) was demonstrated in the reaction with
      Pt(PPh(3))(4) which yielded cis-(PPh(3))(2)PtH(tBu(2)P(CH(2))(4)OB(C(6)F(5))(3))
      12, while the reaction of [SIMesH][tBu(2)P(CH(2))(4)OB(C(6)F(5))(3)] 13 with
      NiCl(2)(DME) and PdCl(2)(PhCN)(2) afforded the complexes [SIMesH](2)[trans
      Cl(2)Ni(tBu(2)PC(4)H(8)OB(C(6)F(5))(3))(2)] 14 and [SIMesH](2)[trans
      PdCl(2)(tBu(2)P(CH(2))(4)OB(C(6)F(5))(3))(2)] 15, respectively, analogous to
      those prepared with 4 and 5. Finally, the reaction of 7 and 13with [(p
      cymene)RuCl(2)](2) proceeds to give the new orange products [SIMesH][(p
      cymene)RuCl(2)(Cy(2)PC(6)F(4)BF(C(6)F(5))(2))] 16 and [SIMesH][(p
      cymene)RuCl(2)(tBu(2)P(CH(2))(4)OB(C(6)F(5))(3))] 17, respectively. Crystal
      structures of 1, 6, 10, 11, 12, and 16 are reported.

PMID- 22458595
TI  - A computerized tomography study of the morphological interrelationship between
      the temporal bones and the craniofacial complex.
AB  - The hypothesis that the temporal bones are at the center of the dynamics of the
      craniofacial complex, directly influencing facial morphology, has been put
      forward long ago. This study examines the role of the spatial positioning of
      temporal bones (frontal and sagittal inclination) in terms of influencing overall
      facial morphology. Several 3D linear, angular and orthogonal measurements
      obtained through computerized analysis of virtual models of 163 modern human
      skulls reconstructed from cone-beam computed tomography images were analyzed and
      correlated. Additionally, the sample was divided into two subgroups based on the
      median value of temporal bone sagittal inclination [anterior rotation group (n =
      82); posterior rotation group (n = 81)], and differences between groups
      evaluated. Correlation coefficients showed that sagittal inclination of the
      temporal bone was significantly (P < 0.01) related to midline flexion,
      transversal width and anterior-posterior length of the basicranium, to the
      anterior-posterior positioning of the mandible and maxilla, and posterior
      midfacial height. Frontal inclination of the temporal bone was significantly
      related (P < 0.01) to basicranium anterior-posterior and transversal dimensions,
      and to posterior midfacial height. In comparison with the posterior rotation
      group, the anterior rotation group presented a less flexed and anterior
      posteriorly longer cranial base, a narrower skull, porion and the articular
      eminence located more superiorly and posteriorly, a shorter posterior midfacial
      height, the palatal plane rotated clockwise, a more retrognathic maxilla and
      mandible, and the upper posterior occlusal plane more inclined and posteriorly
      located. The results suggest that differences in craniofacial morphology are
      highly integrated with differences in the positional relationship of the temporal
      bones. The sagittal inclination of the temporal bone seems to have a greater
      impact on the 3D morphology of the craniofacial complex than frontal inclination.

PMID- 22458596
TI  - Comparison between self-estimated and clinical oral malodor.
AB  - OBJECTIVES: The aims were to evaluate the validity of patients' self-estimation
      and clinical diagnosis of oral malodor and to examine the relationship of oral
      malodor with oral health status. METHODS: The subjects were 252 patients (mean
      age 43.7 +/- 10.7 years) who complained of oral malodor. Oral malodor was
      assessed by patients' self-estimation, organoleptic test and Oral Chroma. Oral
      health status, including dental and periodontal conditions, oral hygiene status
      and flow rate of saliva, was examined. The N-benzoyl-DL-arginine-2-napthilamide
      (BANA) positive bacteria in tongue coating were evaluated by BANA test. A
      Spearman's correlation coefficient was used to test correlation between self
      perceived and clinical oral malodor. The stepwise multiple regression analysis
      was used to assess predictors of patients' self-estimated and clinical oral
      malodor. RESULTS: The percentage of patients who were diagnosed with pseudo
      halitosis was 38.5%. Patients' self-estimated oral malodor was significantly
      correlated with organoleptic test (r = 0.61), H(2)S (r = 0.50) and CH(3)SH (r =
      0.46). There were 47.1% of patients who estimated correctly their oral malodor's
      scores with those by examiner. The highest correspondence was found in patients
      without oral malodor (52.6%), followed by in those with moderate or strong oral
      malodor (46.7%) and in those with slight oral malodor (33.3%). The significant
      predictors of patients' self-estimated and clinical oral malodor were bleeding on
      probing, tongue coating, BANA test and flow rate of saliva. CONCLUSION: Patients'
      self-estimated oral malodor was found to correspond significantly with clinical
      oral malodor and be associated with oral health status. Current findings suggest
      that self-estimation can be used to judge one's own oral malodor.

PMID- 22458597
TI  - The post-pollination ethylene burst and the continuation of floral advertisement
      are harbingers of non-random mate selection in Nicotiana attenuata.
AB  - The self-compatible plant Nicotiana attenuata grows in genetically diverse
      populations after fires, and produces flowers that remain open for 3 days and are
      visited by assorted pollinators. To determine whether and when post-pollination
      non-random mate selection occurs among self and non-self pollen, seed paternity
      and semi-in vivo pollen tube growth were determined in controlled single/mixed
      pollinations. Despite all pollen sources being equally proficient in siring seeds
      in single-genotype pollinations, self pollen was consistently selected in mixed
      pollinations, irrespective of maternal genotype. However, clear patterns of mate
      discrimination occurred amongst non-self pollen when mixed pollinations were
      performed soon after corollas open, including selection against hygromycin B
      resistance (transformation selectable marker) in wild-type styles and for it in
      transformed styles. However, mate choice among pollen genotypes was completely
      shut down in plants transformed to be unable to produce (irACO) or perceive
      (ETR1) ethylene. The post-pollination ethylene burst, which originates primarily
      from the stigma and upper style, was strongly correlated with mate selection in
      single and mixed hand-pollinations using eight pollen donors in two maternal
      ecotypes. The post-pollination ethylene burst was also negatively correlated with
      the continuation of emission of benzylacetone, the most abundant pollinator
      attracting corolla-derived floral volatile. We conclude that ethylene signaling
      plays a pivotal role in mate choice, and the post-pollination ethylene burst and
      the termination of benzylacetone release are accurate predictors, both
      qualitatively and quantitatively, of pre-zygotic mate selection and seed
      paternity.

PMID- 22458598
TI  - Ureteroscopic and extirpative treatment of upper urinary tract urothelial
      carcinoma: a 15-year comprehensive review of 160 consecutive patients.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Upper urinary tract urothelial carcinomas
      (UTUC) have historically been treated with radical, extirpative surgery,
      primarily nephroureterectomy with bladder-cuff excision. In general, there has
      been growing interest in renal preservation, as evidenced by the broadening
      application of nephron-sparing surgery for renal parenchymal tumours. Beyond
      imperative reasons such as tumour in a solitary kidney, bilateral disease, or
      comorbidities preventing radical surgery, there is a growing role for endoscopic
      management of upper tract tumours. The aim has been to obtain similar oncological
      results to those of extirpative surgery, while preserving long-term renal
      function. Properly selecting patients for these therapies, designing specific
      treatments based on a complex presentation, and general information with regard
      to outcomes and risks for patient counselling have been based historically on
      results from relatively small series without long-term follow-up. This study
      reflects all patients with UTUC treated by a single tertiary referral surgeon,
      accrued prospectively over 15 years using the same surgical techniques and
      treatment algorithms throughout the entire study period, with 10-year survival
      data. The consecutively accrued nature and size of the study groups, uniformity
      in treatments, statistical review and long-term follow-up provide baseline
      oncological data that could help frame future study. OBJECTIVE: * To present long
      term oncological outcomes of all patients treated surgically for upper urinary
      tract urothelial carcinoma (UTUC) over a 15-year period. PATIENTS AND METHODS: *
      All patients (N = 160) treated from January 1996 to August 2011 were
      prospectively studied and placed into three distinct groups after initial
      diagnostic ureteroscopy (URS): Group 1: low grade lesions treated with URS (n =
      66); Group 2: high grade lesions palliatively treated with URS (n = 16); and
      Group 3: extirpative surgery (nephroureterectomy [NU]; n = 80). * Statistical
      analysis was performed using Kaplan-Meier methodology to calculate overall (OS),
      cancer-specific (CSS) and metastasis-free survival (MFS). RESULTS: * The median
      patient age at presentation was 73 years, and the mean (range) follow-up time was
      38.2 (1-185) months. At initial diagnostic URS, 71 (44.4%) patients presented
      with high grade and 89 (55.6%) patients presented with low grade disease. * The 2
      , 5- and 10-year CSS rates were 98, 87 and 81% for patients with low grade
      disease, and 97, 87 and 78% for patients treated with URS (Group 1), not
      significantly different from those patients with low grade disease treated with
      NU (Group 3), (P = 0.54). * Of the patients treated with URS for low grade
      disease, 10 (15.2%) progressed to high grade disease at a mean time of 38.5
      months. * Patients with high grade disease treated with NU had a 2-, 5-, and 10
      year CSS of 70, 53 and 38%, with a MFS of 55, 45 and 35%. * Median survival of
      patients with high grade disease treated with palliative URS was 29.2 months with
      a 2-year OS of 54%. * On multivariate analysis only high grade lesion on initial
      presentation was found to be a significant factor (P < 0.001; hazard ratio =
      7.27). CONCLUSIONS: * Grade is the most significant predictor of OS and CSS in
      those with UTUC, regardless of treatment method. * Ureteroscopic and extirpative
      therapy are acceptable options for those with low grade disease showing excellent
      long-term CSS. * Extirpative therapy was found to result in relatively poor long
      term CSS in patients with high grade disease, underscoring the need for adjuvant
      or neoadjuvant therapies.

PMID- 22458600
TI  - S100A4 regulates motility and invasiveness of human esophageal squamous cell
      carcinoma through modulating the AKT/Slug signal pathway.
AB  - The involvement of S100A4 in modulating invasiveness of esophageal squamous cell
      carcinoma (ESCC) cell lines was explored. It was shown that S100A4 expression is
      positively correlated with the degree of invasiveness in human ESCC cells. The
      S100A4-rich EC-1 cells displayed higher migratory and invasive cell behavior
      while ET-1 cells with low S100A4 expression levels displayed lower migratory and
      invasive cell behavior. S100A4 silencing by small interfering (siRNA) in EC-1
      cells induced E-cadherin expression, and overexpression of S100A4 in a lowly
      invasive TE-1 cells suppressed E-cadherin expression. It is suggested that S100A4
      silencing inhibit invasion via E-cadherin upregulation, and overexpression of
      S100A4 promote invasion via E-cadherin downregulation in ESCC cells. Compared
      with the vector-transfected cells, S100A4 silencing in EC-1 cells showed reduced
      ability of migration and invasiveness, and overexpression of S100A4 in TE-1 cells
      showed increased ability of migration and invasiveness via wound-healing and
      Transwell assay, and pseudometastatic model assay. Furthermore, re-expression of
      S100A4 could increase the invasive phenotypes in S100A4 siRNA transfected EC-1
      cells, and S100A4 silencing could decrease the invasive phenotypes in S100A4
      circular DNA (cDNA) transfected TE-1 cells. It was found that Slug is
      downregulated in S100A4 siRNA transfected EC-1 cells, and Slug is upregulated in
      S100A4 cDNA transfected TE-1 cells. It was also discovered S100A4 cDNA induced
      protein kinase B (AKT) phosphorylation at Serine-473(phospho-AKT [p-AKT]) levels,
      followed by the Slug upregulation, and S100A4 siRNA decreases the phospho-AKT
      levels, followed by the Slug downregulation. The data suggested that S100A4 could
      regulate migratory and invasive behavior of human ESCC cells through modulating
      AKT/Slug pathway.

PMID- 22458599
TI  - Pcp4l1 contains an auto-inhibitory element that prevents its IQ motif from
      binding to calmodulin.
AB  - Purkinje cell protein 4-like 1 (Pcp4l1) is a small neuronal IQ motif protein
      closely related to the calmodulin-binding protein Pcp4/PEP-19. PEP-19 interacts
      with calmodulin via its IQ motif to inhibit calmodulin-dependent enzymes and we
      hypothesized Pcp4l1 would have similar properties. Surprisingly, full-length
      Pcp4l1 does not interact with calmodulin in yeast two-hybrid or pulldown
      experiments yet a synthetic peptide constituting only the IQ motif of Pcp4l1
      binds calmodulin and inhibits calmodulin-dependent kinase II. A nine-residue
      glutamic acid-rich sequence in Pcp4l1 confers these unexpected properties. This
      element lies outside the IQ motif and its deletion or exchange with the
      homologous region of PEP-19 restores calmodulin binding. Conversion of a single
      isoleucine (Ile36) within this motif to phenylalanine, the residue present in PEP
      19, imparts calmodulin binding onto Pcp4l1. Moreover, only aromatic amino acid
      substitutions at position 36 in Pcp4l1 allow binding. Thus, despite their
      sequence similarities PEP-19 and Pcp4l1 have distinct properties with the latter
      harboring an element that can functionally suppress an IQ motif. We speculate
      Pcp4l1 may be a latent calmodulin inhibitor regulated by post-translational
      modification and/or co-factor interactions.

PMID- 22458602
TI  - Construct validation of the readiness for interprofessional learning scale: a
      Rasch and factor analysis.
AB  - In order to improve efficiency and collaboration in healthcare service provision,
      it is recommended that students engage in interprofessional education; that is,
      learning with, from and about professions other than one's own profession. Such
      endeavors are often impeded by pre-existing attitudes; therefore, self-reporting
      scales such as the Readiness for Interprofessional Learning Scale (RIPLS) have
      often been used in studies to gauge perspectives. The original 19-item version of
      the RIPLS was completed by 418 undergraduate healthcare students from a large
      Australian University. A principal component analysis with a varimax rotation was
      first carried out followed by Rasch model analyses on the RIPLS data. A four
      factor solution was produced by the initial factor analysis, which did not
      correspond to the original three-factor solution identified by the RIPLS authors.
      The subsequent Rasch analyses of the four-factor structure produced two
      misfitting items, and reconfirmed a four-factor solution. The 17-item four-factor
      RIPLS demonstrated a good fit to the Rasch model and exhibited good reliability
      and dimensionality. A four-factor RIPLS solution was identified and confirmed via
      two statistical approaches. Two items were found not to fit the new RIPLS four
      factor structure and it is recommended that they be discarded. Further refinement
      of the RIPLS is recommended.

PMID- 22458601
TI  - Effect of hawthorn standardized extract on flow mediated dilation in
      prehypertensive and mildly hypertensive adults: a randomized, controlled cross
      over trial.
AB  - BACKGROUND: Hawthorn extract has been used for cardiovascular diseases for
      centuries. Recent trials have demonstrated its efficacy for the treatment of
      heart failure, and the results of several small trials suggest it may lower blood
      pressure. However, there is little published evidence to guide its dosing. The
      blood pressure lowering effect of hawthorn has been linked to nitric oxide
      mediated vasodilation. The aim of this study was to investigate the relationship
      between hawthorn extract dose and brachial artery flow mediated dilation (FMD),
      an indirect measure of nitric oxide release. METHODS: We used a four-period cross
      over design to evaluate brachial artery FMD in response to placebo or hawthorn
      extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract).
      Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and
      placebo were assigned to each participant. Doses were taken twice daily for 3 1/2
      days followed by FMD and a 4-day washout before proceeding to the next dosing
      period. RESULTS: Twenty-one prehypertensive or mildly hypertensive adults
      completed the study. There was no evidence of a dose-response effect for our main
      outcome (FMD percent) or any of our secondary outcomes (absolute change in
      brachial artery diameter and blood pressure). Most participants indicated that if
      given evidence that hawthorn could lower their blood pressure, they would be
      likely to use it either in conjunction with or instead of lifestyle modification
      or anti-hypertensive medications. CONCLUSION: We found no evidence of a dose
      response effect of hawthorn extract on FMD. If hawthorn has a blood pressure
      lowering effect, it is likely to be mediated via an NO-independent mechanism.
      TRIAL REGISTRATION: This trial has been registered with ClinicalTrials.gov, a
      service of the U.S. National Institutes of Health: NCT01331486.

PMID- 22458603
TI  - Combinatorial aid for underprivileged scaffolds: solution and solid-phase
      strategies for a rapid and efficient access to novel aza-diketopiperazines (Aza
      DKP).
AB  - An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP,
      triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly
      Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4-triazine-3,6
      diones has been synthesized starting from Fmoc-l-Pro-OH and various Fmoc-l-amino
      acids. To extend the practical value of this class of dipeptidomimetics, a
      general solid-phase synthesis approach amenable to library production was
      developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the
      resins in TFA/water mixture at room temperature enabled the rapid and
      quantitative cyclization/release highly pure triazinediones. The conformational
      preferences and the spatial organization of the three substituents of a
      representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by
      X-ray diffraction and (1)H NMR spectroscopy. 

PMID- 22458605
TI  - A novel ABO allele caused by an in-frame triplet deletion in ABO gene.

PMID- 22458604
TI  - Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk.
AB  - Ibogaine, an alkaloid derived from the African shrub Tabernanthe iboga, has shown
      promising anti-addictive properties in animals. Anecdotal evidence suggests that
      ibogaine is also anti-addictive in humans. Thus, it alleviates drug craving and
      impedes relapse of drug use. Although not licensed as therapeutic drug, and
      despite evidence that ibogaine may disturb the rhythm of the heart, this alkaloid
      is currently used as an anti-addiction drug in alternative medicine. Here, we
      report that therapeutic concentrations of ibogaine reduce currents through human
      ether-a-go-go-related gene potassium channels. Thereby, we provide a mechanism by
      which ibogaine may generate life-threatening cardiac arrhythmias. 

PMID- 22458606
TI  - Sample-level enrichment analysis unravels shared stress phenotypes among multiple
      cancer types.
AB  - BACKGROUND: Adaptation to stress signals in the tumor microenvironment is a
      crucial step towards carcinogenic phenotype. The adaptive alterations attained by
      cells to withstand different types of insults are collectively referred to as the
      stress phenotypes of cancers. In this manuscript we explore the interrelation of
      different stress phenotypes in multiple cancer types and ask if these phenotypes
      could be used to explain prognostic differences among tumor samples. METHODS: We
      propose a new approach based on enrichment analysis at the level of samples
      (sample-level enrichment analysis - SLEA) in expression profiling datasets.
      Without using a priori phenotypic information about samples, SLEA calculates an
      enrichment score per sample per gene set using z-test. This score is used to
      determine the relative importance of the corresponding pathway or module in
      different patient groups. RESULTS: Our analysis shows that tumors significantly
      upregulating genes related to chromosome instability strongly correlate with
      worse prognosis in breast cancer. Moreover, in multiple tumor types, these tumors
      upregulate a senescence-bypass transcriptional program and exhibit similar stress
      phenotypes. CONCLUSIONS: Using SLEA we are able to find relationships between
      stress phenotype pathways across multiple cancer types. Moreover we show that
      SLEA enables the identification of gene sets in correlation with clinical
      characteristics such as survival, as well as the identification of biological
      pathways/processes that underlie the pathology of different cancer subgroups.

PMID- 22458608
TI  - Three-dimensional chiral plasmonic oligomers.
AB  - The living world is chiral. Chirality or the handedness of a structure or
      molecule is at the heart of life itself. Recently, it has been shown that
      plasmonic structures exhibit unprecedented and gigantic chiral optical responses.
      Here we show that truly three-dimensional arrangements of plasmonic "meta-atoms"
      only exhibit a chiral optical response if similar plasmonic "atoms" are arranged
      in a handed fashion as we require resonant plasmonic coupling. Moreover, we
      demonstrate that such particle groupings, similarly to molecular systems, possess
      the capability to encode their three-dimensional arrangement in unique and well
      modulated spectra making them ideal candidates for a three-dimensional chiral
      plasmon ruler. Our results are crucial for the future design and improvement of
      plasmonic chiral optical systems, for example, for ultrasensitive enantiomer
      sensing on the single molecule level.

PMID- 22458607
TI  - Carotid endarterectomy and carotid artery stenting utilization trends over time.
AB  - BACKGROUND: Carotid endarterectomy (CEA) has been the standard in atherosclerotic
      stroke prevention for over 2 decades. More recently, carotid artery stenting
      (CAS) has emerged as a less invasive alternative for revascularization. The
      purpose of this study was to investigate whether an increase in stenting
      parallels a decrease in endarterectomy, if there are specific patient factors
      that influence one intervention over the other, and how these factors may have
      changed over time. METHODS: Using a nationally representative sample of US
      hospital discharge records, data on CEA and CAS procedures performed from 1998 to
      2008 were obtained. In total, 253,651 cases of CEA and CAS were investigated for
      trends in utilization over time. The specific data elements of age, gender, payer
      source, and race were analyzed for change over the study period, and their
      association with type of intervention was examined by multiple logistic
      regression analysis. RESULTS: Rates of intervention decreased from 1998 to 2008
      (P < 0.0001). Throughout the study period, endarterectomy was the much more
      widely employed procedure. Its use displayed a significant downward trend (P <
      0.0001), with the lowest rates of intervention occurring in 2007. In contrast,
      carotid artery stenting displayed a significant increase in use over the study
      period (P < 0.0001), with the highest intervention rates occurring in 2006. Among
      the specific patient factors analyzed that may have altered utilization of CEA
      and CAS over time, the proportion of white patients who received intervention
      decreased significantly (P < 0.0001). In multivariate modeling, increased age,
      male gender, white race, and earlier in the study period were significant
      positive predictors of CEA use. CONCLUSIONS: Rates of carotid revascularization
      have decreased over time, although this has been the result of a reduction in CEA
      despite an overall increase in CAS. Among the specific patient factors analyzed,
      age, gender, race, and time were significantly associated with the utilization of
      these two interventions.

PMID- 22458609
TI  - Chemo- and regioselective assembly of polysubstituted pyridines and isoquinolines
      from isocyanides, arynes, and terminal alkynes.
AB  - We have disclosed a general and efficient synthetic strategy for polysubstituted
      pyridines and isoquinolines with high chemo- and regioselectivity. In this
      methodology, 1-alkynyl imines act as the key compound to undergo a sequential
      alkynyl imine-allenyl imine isomerization/aza-Diels-Alder reaction/aromatization.
      In the first place, 1-alkynyl imines were formed in situ by a highly selective
      multicomponent reaction of isocyanides, arynes, and terminal alkynes and reacted
      with another molecule of arynes or terminal alkynes to furnish target
      heterocyclic products in a highly efficient and atom-economic manner. On the
      other hand, we attempted to prepare 1-alkynyl imines by other approaches to
      undergo a similar reaction sequence to afford polysubstituted pyridines and
      isoquinolines with a wider range. Different from the first approach, the second
      approach utilized the preprepared 1-alkynyl imines to introduce the related
      different substitutents into the final products: arynes or terminal alkynes
      bearing substituents different from those of 1-alkynyl imines have been
      successfully applied for the synthesis a wide variety of pyridines and
      isoquinolines with diversity.

PMID- 22458610
TI  - Control of large institutional scabies outbreaks.
AB  - BACKGROUND: Scabies outbreaks in community facilities may reach large dimensions
      and take a protracted course. Highly contagious crusted scabies is a major cause
      of nosocomial outbreaks. PATIENTS AND METHODS: On the occasion of an extensive
      scabies outbreak in a north Bavarian sheltered workshop and its associated
      residential homes with over 500 exposed individuals, a multifaceted control
      strategy was developed and pursued. Knowledge from a comprehensive review of the
      literature was utilized. RESULTS: Our successful scabies elimination concept
      includes: 1) Careful organization (formation of an outbreak management team,
      registration and information of all exposed individuals, prospective time
      management, financial calculation); 2) simultaneous clinical examination of all
      individuals at risk; 3) synchronous topical treatment of all exposed individuals
      with permethrin 5 % cream on day 0, repeated treatment of proven and doubtful
      cases on days 1 and 14; systemic treatment of selected cases with oral
      ivermectin; 4) decontamination and quarantine measures; 5) follow-up
      investigations and repeated treatment if indicated. CONCLUSIONS: Management of
      large institutional scabies outbreaks requires a high degree of motivation,
      communication skills and perseverance.

PMID- 22458611
TI  - Synthesis and biological activity of potent HIV-1 protease inhibitors based on
      Phe-Pro dihydroxyethylene isosteres.
AB  - Peptidomimetic inhibitors of HIV-1 PR are still a key resource in the fight
      against AIDS. Here we describe the synthesis and biological activity of HIV-1 PR
      inhibitors based on four novel dihydroxyethylene isosteres of the Phe-Pro and Pro
      Pro dipeptides. The isosteres, containing four stereogenic centers, were
      synthesized in high yield and excellent stereoselectivity via the cyclization of
      epoxy amines derived from alpha-amino acids. The inhibitors were assembled by
      coupling the isosteres with suitable flanking groups and were screened against
      recombinant HIV PR showing activities in the subnanomolar to micromolar range.
      Two Phe-Pro-based inhibitors active at the nanomolar level were further
      investigated: both inhibitors combine the ability to suppress HIV-1 replication
      in infected MT-2 cells with low cytotoxicity against the same cells, thereby
      displaying a high therapeutic index. These results demonstrate the potential of
      the new Phe-Pro dihydroxyethylene isostere as a core unit of powerful HIV-1 PR
      inhibitors.

PMID- 22458612
TI  - How can innovative uses of technology be harnessed to improve medication
      adherence?

PMID- 22458613
TI  - Economic analyses of diagnostics for tuberculosis: what's the point?

PMID- 22458615
TI  - Patient preferences for psoriasis treatment: process characteristics considered
      more important than outcome attributes.
AB  - In a recent paper by Schaarschmidt et al., patients with moderate-to-severe
      psoriasis completed a conjoint analysis survey (discrete choice experiment) to
      determine which factors had influenced their choice of treatment, and the
      relative importance of each factor. They also assessed how socioeconomic and
      demographic factors affected patient choice. Using relative importance scores,
      treatment location was found to be the more important attribute to patients,
      followed by probability of benefit and method of delivery.

PMID- 22458616
TI  - Measuring and managing patient expectations for breast reconstruction: impact on
      quality of life and patient satisfaction.
AB  - The goal of postmastectomy breast reconstruction is to restore a woman's body
      image and to satisfy her personal expectations regarding the results of surgery.
      Studies in other surgical areas have shown that unrecognized or unfulfilled
      expectations may predict dissatisfaction more strongly than even the technical
      success of the surgery. Patient expectations play an especially critical role in
      elective procedures, such as cancer reconstruction, where the patient's primary
      motivation is improved health-related quality of life. In breast reconstruction,
      assessment of patient expectations is therefore vital to optimal patient care.
      This report summarizes the existing literature on patient expectations regarding
      breast reconstruction, and provides a viewpoint on how this field can evolve.
      Specifically, we consider how systematic measurement and management of patient
      expectations may improve patient education, shared medical decision-making and
      patient perception of outcomes.

PMID- 22458617
TI  - The importance of integrating medication adherence into pharmacoeconomic
      analyses: the example of osteoporosis.
AB  - Adherence to medications is poor and suboptimal in many chronic diseases.
      Nonadherence can reduce treatment effectiveness and can have an impact on
      healthcare costs. As a consequence, it may alter the cost-effectiveness of drug
      therapies. This article emphasizes the importance of integrating medication
      compliance and persistence into pharmacoeconomic evaluations, using osteoporosis
      as an example. A limited number of studies carried out to date have suggested
      important economic implications of poor adherence to osteoporosis medications.
      Therefore, compliance and persistence should be an integral part of clinical
      studies and pharmacoeconomic analyses in order to estimate the cost-effectiveness
      of drug therapies in current community practice. Measuring adherence and
      incorporating it into health economic modeling may, however, pose particular
      challenges.

PMID- 22458618
TI  - Patient preferences and healthcare outcomes: an ecological perspective.
AB  - This article examines the nature of patients' preferences for healthcare and
      whether clinician accommodation of patient preferences influences health
      outcomes. First, we provide a conceptualization of patient preferences along with
      their key attributes. Second, we review research on the relationship between
      health outcomes and patient preferences for treatments and for the process of
      care (e.g., preferred involvement in decision-making). Third, following a
      critique of this literature, we present an ecological model of patient
      preferences that, while acknowledging that patient preferences may emerge from
      various contexts (e.g., family or media exposure), we focus on the important role
      that clinical encounters and patients' health-related experiences play in the
      elicitation and construction of patient preferences. Fourth, we propose two
      pathways, one behavioral (adherence) and the other psychological (sense of
      autonomy or satisfaction with decision), through which meeting patient
      preferences could lead to better health outcomes. Fifth, we discuss how
      preferences can be elicited and clarified through patient-centered conversations.
      We conclude with implications for future research and clinical practice.

PMID- 22458620
TI  - The process of reconciliation: evaluation of guidelines for translating quality
      of-life questionnaires.
AB  - Reconciliation refers to the process through which two or more independent
      forward translations are merged into one single translation. This critical step
      in the translation process is difficult to formalize. The purpose of this review
      is to analyze how reconciliation is specified in leading guidelines for the
      translation of quality-of-life questionnaires and other patient-reported outcome
      forms with regard to the number and qualifications of individuals involved, the
      processes followed, as well as the criteria applied. In general, relatively
      little attention has been paid to characterizing the process in detail. Based on
      these findings, we specify criteria to be followed.

PMID- 22458619
TI  - Successful implementation of cognitive interviews in special populations.
AB  - The cognitive interview, with a focus on debriefing methods, was developed in the
      1980s to identify sources of potential response error in surveys or
      questionnaires. With the release of the final US FDA guidance, titled 'Patient
      Reported Outcome Measures: Use in Medical Product Development to Support Labeling
      Claims', cognitive interviews have gained importance and relevance both for
      concept elicitation and debriefing purposes in the context of instrument
      development. This article is intended as a guide for the researcher working with
      special populations in methods to foster successful cognitive interviews that
      meet FDA standards. While many of these techniques are broadly applicable,
      specific recommendations are provided for working with pediatric and cognitively
      challenged populations, as well as with individuals with communication
      difficulties.

PMID- 22458621
TI  - Determining quality of life in stroke survivors.
AB  - Post-stroke health-related quality of life (HRQoL) reflects a comprehensive view
      of subjective health and a measure of a person's perceived physical, mental and
      social health following stroke. Generic scales may enable comparisons between
      groups of patients with a diverse range of conditions, although they may
      underestimate the effect of stroke owing to its limited content validity. Stroke
      specific HRQoL measures were designed to assess relevant domains that are
      important to stroke patients. The Stroke Impact Scale, the Stroke Specific
      Quality of Life scale and The Burden of Stroke Scale are specific HRQoL
      instruments developed in the last decade. Demographic factors, comorbidity,
      stroke severity, disability and psychosocial factors (e.g., post-stroke
      depression and social support) are significant predictors of HRQoL in stroke
      survivors. Stroke caregiver burden and HRQoL are inversely correlated. HRQoL
      measures are increasingly used to evaluate the effect of some therapeutic
      interventions in stroke survivors.

PMID- 22458622
TI  - Comparison of the EORTC QLQ-BM22 and the FACT-BP for assessment of quality of
      life in cancer patients with bone metastases.
AB  - INTRODUCTION: Maintenance or improvement in quality of life (QoL) is the main
      goal of palliative treatments for bone metastases. Validated and comprehensive
      tools assessing QoL for specific patient subgroups are required in order to
      accurately assess and make informed decisions about palliative treatments. The
      European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire for patients with bone metastases (QLQ-BM22) and the Functional
      Assessment of Cancer Therapy Quality of Life Measurement in patients with bone
      pain (FACT-BP) are the only two palliative QoL tools available that have been
      validated for use specifically for bone metastases patients. The purpose of this
      study was to compare the development and characteristics of these two tools, as
      well as their current use in palliative research. METHODS: Studies detailing the
      development process for the QLQ-BM22 and the FACT-BP were identified. A
      comparison between both questionnaires in terms of development, characteristics,
      validation and use was conducted. RESULTS: The QLQ-BM22 was developed with
      collaboration from patients, healthcare professionals and review of the
      literature, whereas the FACT-BP was created strictly through interviews with
      patients. Scoring, organization, response options and item format are different;
      however, recall period is the same. Both tools showed good internal consistency
      and construct validity. The QLQ-BM22 showed good test-retest reliability, while
      this has not been tested with the FACT-BP. The QLQ-BM22 has been internationally
      validated among a large sample of patients undergoing a variety of treatments,
      demonstrating its ability of detect meaningful QoL changes in diverse bone
      metastases populations. On the other hand, the FACT-BP demonstrated high internal
      consistency at all assessments, indicating that it may be utilized as a stand
      alone measure of bone pain. CONCLUSION: Both the QLQ-BM22 and FACT-BP are
      designed for assessment of QoL issues specific to cancer patients with bone
      metastases. Each instrument has unique strengths and weaknesses and choice
      between these tools is dependent on the investigator and study needs.

PMID- 22458623
TI  - Quality of life and burden in caregivers for patients with Parkinson's disease:
      concepts, assessment and related factors.
AB  - Caregivers of Parkinson's disease patients face responsibilities stemming from
      providing assistance to a person, usually a family member, who suffers a
      progressively disabling disease characterized by both motor and nonmotor
      symptoms. These circumstances impact on the physical, emotional and psychosocial
      aspects of the caregivers' lives and, therefore, on their quality of life (QoL).
      Studies have identified factors related to caregivers' global QoL and health
      related QoL, causing caregivers distress and affecting their QoL. These factors
      are related to patients' and caregivers' characteristics and may be classified as
      sociodemographic, psychological and disease related. Caregiver's burden refers to
      the multiplicity of difficulties ensuing as a consequence of caring, including,
      for example, health problems, modification of habits, economic loss and QoL
      deterioration. Therefore, burden-related factors are also briefly reviewed. The
      implementation of effective interventions to preserve the caregiver's wellbeing
      and allow the patients to remain at home and be properly assisted is a pragmatic
      consequence of this knowledge.

PMID- 22458624
TI  - Simplifying rules for optimal allocation of preventive care resources.
AB  - Given the limited resources for preventive care, policy-makers need to consider
      the efficiency/cost-effectiveness of preventive measures, such as drugs and
      vaccines, when allocating preventive care resources. However, in many settings
      only limited information on lifetime costs and effects of preventive measures
      exists. Therefore, it seems useful to provide policy-makers with some simplifying
      rules when allocating preventive care resources. The purpose of this article is
      to investigate the relevance of risk and severity of the disease to be prevented
      for the optimal allocation of preventive care resources. The report shows - based
      on a constrained optimization model - that optimal allocation of preventive care
      resources does, in fact, depend on both factors. Resources should be allocated to
      the prevention of diseases with a higher probability of occurrence or larger
      severity. This article also identifies situations where preventive care resources
      should be allocated to the prevention of less severe disease.

PMID- 22458625
TI  - Projected referral to other healthcare services in an outpatient palliative
      radiotherapy clinic.
AB  - AIMS: To investigate the projected referral to other healthcare services in an
      outpatient palliative radiotherapy clinic. METHODS: Patients referred for
      palliative radiotherapy from 1999 to 2002 inclusive and 2007 to 2009 inclusive
      were evaluated. The Edmonton Symptom Assessment System, which assesses nine
      symptoms, was completed by 1439 patients prior to radiotherapy consultation. The
      numeric scale was converted into a categorical scale of none, mild, moderate and
      severe. Patients with moderate-to-severe symptoms were identified as potential
      referrals to other healthcare services. RESULTS: Tiredness (66%), poor sense of
      wellbeing (64%), pain (57%) and poor appetite (52%) had the most patients scoring
      in the moderate-to-severe range. Moderate-to-severe anxiety and depression
      occurred in 39 and 30% of patients, respectively, reflecting the percentage of
      projected referrals for symptom and/or psychosocial management. CONCLUSION:
      Cancer symptoms are complex, and a multidisciplinary and collaborative approach
      should be taken to provide timely management and maintain patients' quality of
      life.

PMID- 22458627
TI  - Time trend in tumour size and characteristics of anaplastic thyroid carcinoma.
AB  - OBJECTIVE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive
      malignancies. Nevertheless, there have been reports that some patients experience
      long-term survival and those in whom ATCs of small size are often detected. We
      evaluated the time trend of characteristics of ATC such as size and association
      with coexistent differentiated thyroid carcinoma (DTC). We also found the
      characteristics of patients showing long-term survival. DESIGN AND PATIENTS: This
      is a retrospective observational cohort study from the two major tertiary
      referral hospitals in Seoul, Korea. Ninety-five patients who had been diagnosed
      with ATC from 1995 to 2010 were included. We classified them into three groups
      according to the time of initial diagnosis: group 1 (1995-1999), group 2 (2000
      2004) and group 3 (2005-2010). RESULTS: The mean tumour size decreased
      significantly according to groups; 6.2, 5.5 and 4.0 cm in group 1, 2 and 3,
      respectively (P = 0.02). The frequency of cases with coexistent DTC increased;
      10.3%, 35.1% and 48.3% in group 1, 2 and 3, respectively (P = 0.02). Fifteen of
      95 patients survived more than 24 months, and among them, 13 are still alive who
      underwent curative surgery. Among 15 long-term survivors, nine patients with ATC
      arising from DTC had ATC tumour portion less than 1 cm. Another five patients
      with ATC without coexistent DTC had relatively small-sized tumours (1.0-4.0 cm).
      CONCLUSION: The tumour size of ATC decreased, and cases with coexistent DTC
      increased over the last two decades. We found that patients with ATC showing long
      term survival are those who had atypical presentations such as anaplastic
      transformation in early stage of DTC or small size of tumours without coexistent
      DTC.

PMID- 22458628
TI  - A comparison of cone beam computed tomography and conventional periapical
      radiography at detecting peri-implant bone defects.
AB  - OBJECTIVE: To compare the diagnostic accuracy of conventional periapical
      radiography and cone beam computed tomography (CBCT) at detecting peri-implant
      bone defects. MATERIALS AND METHODS: Implants were placed in fresh bovine ribs in
      osteotomy sites of varying diameter (five with no peri-implant space, five with a
      0.35 mm space, five with a 0.675 mm space) and imaged using (i) digital long cone
      periapical radiographs (LCPAs), (ii) limited volume CBCT using 3D Accuitomo
      80((r)) and (iii) large volume CBCT using i-CAT Next Generation((r)). Images from
      each were randomly presented to nine examiners on two occasions. Confidence in
      diagnosing the presence or absence of a peri-implant radiolucency was recorded on
      a five-point scale. Receiver Operating Characteristic (ROC) analysis and Kappa
      tests were performed. RESULTS: Digital LCPAs were better at diagnosing a peri
      implant bone defect when the peri-implant space was 0.35 mm (P < 0.02). As the
      peri-implant space increased to 0.675 mm, there was no significant difference in
      diagnostic accuracy between the three imaging methods. Sensitivity of LCPAs (100)
      and Accuitomo (97.8) was better than i-CAT (64.4) (P < 0.02). LCPAs and i-CAT had
      significantly better specificity and positive predictive value than Accuitomo.
      The negative predictive value of LCPA was significantly better than i-CAT. LCPAs
      showed better intra-examiner and inter-examiner agreement than CBCT. CONCLUSION:
      Within the limitations of this study, LCPAs are a reliable and valid method of
      detecting circumferential peri-implant bone defects and performed significantly
      better than CBCT.

PMID- 22458629
TI  - Management of venous malformations with percutaneous radiofrequency thermal
      ablation.
AB  - BACKGROUND:   Multiple treatment options exist for venous malformations (VMs),
      but each treatment has its own deficiencies. Radiofrequency ablation (RFA) is an
      emerging technology which may be an effective new technique for treatment of VMs.
      OBJECTIVES: To study the effect of RFA on VMs. METHODS: We reviewed patients
      treated with RFA for VM followed by a blinded retrospective analysis of serial
      photographs taken during the course of their therapy. Questionnaires were used to
      evaluate perceived therapeutic response and complications of this treatment.
      RESULTS: Sixteen patients with complete data and photographic documentation were
      involved in this study. Complete resolution (> 90%) was obtained in two patients.
      Significant improvement (75-90%) of the treated lesion occurred in eight
      patients. Moderate improvement (50-75%) was obtained in one patient and little
      improvement in three patients. Two patients had no response. Most VMs improved,
      with a mean +/- SD size change score of 2.6 +/- 1.3 and overall score of 5.1 +/-
      2.4. No serious complication was observed in any of our patients and no evidence
      of recurrence was observed in any case. CONCLUSIONS: Percutaneous RFA, as a
      minimally invasive and safe treatment, may provide an alternative treatment for
      VM and other skin diseases. There should be a randomized trial undertaken,
      comparing RFA with other treatments, to assess outcome.

PMID- 22458632
TI  - Ashy dermatosis with prior pruritic and scaling skin lesions.

PMID- 22458630
TI  - Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in
      lingual neuropathic pain mechanisms in rats.
AB  - BACKGROUND: It has been reported that the P2Y12 receptor (P2Y12R) is involved in
      satellite glial cells (SGCs) activation, indicating that P2Y12R expressed in SGCs
      may play functional roles in orofacial neuropathic pain mechanisms. However, the
      involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown.
      We therefore studied the reflex to noxious mechanical or heat stimulation of the
      tongue, P2Y12R and glial fibrillary acidic protein (GFAP) immunohistochemistries
      in the trigeminal ganglion (TG) in a rat model of unilateral lingual nerve crush
      (LNC) to evaluate role of P2Y12R in SGC in lingual neuropathic pain. RESULTS: The
      head-withdrawal reflex thresholds to mechanical and heat stimulation of the
      lateral tongue were significantly decreased in LNC-rats compared to sham-rats.
      These nocifensive effects were apparent on day 1 after LNC and lasted for 17
      days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons
      encircled with GFAP-immunoreactive (IR) cells significantly increased in the
      ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC,
      P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN)-IR
      cells (i.e. neurons) in TG. After 3 days of successive administration of the
      P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG
      neurons encircled with GFAP-IR cells was significantly decreased coincident with
      a significant reversal of the lowered head-withdrawal reflex thresholds to
      mechanical and heat stimulation of the tongue compared to vehicle-injected rats.
      Furthermore, after 3 days of successive administration of the P2YR agonist 2
      MeSADP into the TG in naive rats, the mean relative number of TG neurons
      encircled with GFAP-IR cells was significantly increased and head-withdrawal
      reflex thresholds to mechanical and heat stimulation of the tongue were
      significantly decreased in a dose-dependent manner compared to vehicle-injected
      rats. CONCLUSIONS: The present findings provide the first evidence that the
      activation of P2Y12R in SGCs of TG following lingual nerve injury is involved in
      the enhancement of TG neuron activity and nocifensive reflex behavior, resulting
      in neuropathic pain in the tongue.

PMID- 22458633
TI  - Measuring dynamics in weakly structured regions of proteins using microfluidics
      enabled subsecond H/D exchange mass spectrometry.
AB  - This work introduces an integrated microfluidic device for measuring rapid H/D
      exchange (HDX) in proteins. By monitoring backbone amide HDX on the millisecond
      to low second time scale, we are able to characterize conformational dynamics in
      weakly structured regions, such as loops and molten globule-like domains that are
      inaccessible in conventional HDX experiments. The device accommodates the entire
      MS-based HDX workflow on a single chip with residence times sufficiently small
      (ca. 8 s) that back-exchange is negligible (<=5%), even without cooling.
      Components include an adjustable position capillary mixer providing a variable
      time labeling pulse, a static mixer for HDX quenching, a proteolytic microreactor
      for rapid protein digestion, and on-chip electrospray ionization (ESI). In the
      present work, we characterize device performance using three model systems, each
      illustrating a different application of 'time-resolved' HDX. Ubiquitin is used to
      illustrate a crude, high throughput structural analysis based on a single
      subsecond HDX time-point. In experiments using cytochrome c, we distinguish
      dynamic behavior in loops, establishing a link between flexibility and
      interactions with the heme prosthetic group. Finally, we localize an unusually
      high 'burst-phase' of HDX in the large tetrameric enzyme DAHP synthase to a
      'molten globule-like' region surrounding the active site.

PMID- 22458631
TI  - Assembly of the five-way junction in the ribosomal small subunit using hybrid MD
      Go simulations.
AB  - Assembly of the bacterial ribosomal small subunit (SSU) begins with the folding
      of the five-way junction upon interaction with the primary binding protein S4.
      This complex contains the largest contiguous molecular signature, which is a
      conserved feature in all bacterial 16S rRNAs. In a previous study, we used all
      atom molecular dynamics simulations to demonstrate that the co-evolving signature
      in the N-terminus of S4 is intrinsically disordered and capable of accelerating
      the binding process through a fly casting mechanism. In this paper, comparisons
      between the all-atom MD simulations and FRET experiments identify multiple
      metastable conformations of the naked five-way junction without the presence of
      S4. Furthermore, we capture the simultaneous folding and binding of the five-way
      junction and r-protein S4 by use of a structure-based Go potential implemented
      within the framework of the all-atom molecular dynamics CHARMM force field.
      Different folding pathways are observed for the refolding of the five-way
      junction upon partial binding of S4. Our simulations illustrate the complex
      nature of RNA folding in the presence of a protein binding partner and provide
      insight into the role of population shift and the induced fit mechanisms in the
      protein:RNA folding and binding process.

PMID- 22458634
TI  - Historical carbon footprinting and implications for sustainability planning: a
      case study of the Pittsburgh region.
AB  - This study estimates fossil-based CO(2) emissions and energy use from 1900-2000
      for Allegheny County, PA. Total energy use and emissions increased from 1900 to
      1970, reflecting the significant industrial, economic, and population growth that
      occurred in Allegheny County. From 1970 to 2000, Allegheny County experienced a
      30% decrease in total emissions and energy use from peak values, primarily
      because of a decline in industrial activity (40% decrease in value added) and the
      loss of a quarter of its population. Despite these dramatic economic and
      demographic transitions, per capita emissions remained stable from 1970 to 2000,
      buoyed by relatively stable or slightly increasing emissions in the commercial
      and transportation sectors. Allegheny County's history suggests the scale of
      change needed to achieve local emissions reductions may be significant; given
      years of major technological, economic, and demographic changes, per capita
      emissions in 1940 were nearly the same in 2000. Most local governments are
      planning emissions reductions rates that exceed 1% per year, which deviate
      significantly from historical trends. Our results suggest additional resources
      and improved planning paradigms are likely necessary to achieve significant
      emissions reductions, especially for areas where emissions are still increasing.

PMID- 22458635
TI  - Comparison of optic disc parameters using spectral domain cirrus high-definition
      optical coherence tomography and confocal scanning laser ophthalmoscopy in normal
      eyes.
AB  - PURPOSE: To compare Cirrus HD - optical coherence tomography (HD-OCT) with
      confocal scanning laser ophthalmoscopy (HRT 3) for analysis of optic disc
      parameters in healthy eyes. METHODS: In 126 subjects, cup volume (CV), vertical
      cup/disc ratio (CDR), neuroretinal rim area (NRA), cup area (CA) and optic disc
      area (ODA) were measured with the Cirrus HD-OCT and HRT 3. These optic disc
      parameters were chosen for statistical analysis because they can be analysed in
      both OCT and HRT 3 and they are widely used parameters for glaucoma assessment.
      RESULTS: Mean values and significances of paired t-tests for OCT and HRT were for
      CV: 0.099 +/- 0.11 versus 0.082 +/- 0.10 (p < 0.001), CA: 0.42 +/- 0.31 versus
      0.39 +/- 0.31 (p < 0.001), CDR: 0.36 +/- 0.17 versus 0.27 +/- 0.21 (p < 0.001).
      NRA and ODA were not significantly different between instruments. The Pearson
      coefficients were 0.905 (CV), 0.824 (CA), 0.734 (CDR), 0.295 (NRA) and 0.378
      (ODA). CONCLUSION: To our interpretation, the delineation of the optic disc
      border is error-prone with both instruments and all parameters directly depending
      on it are thus poorly correlated. However, the determination of the optic disc
      excavation (CV and CA) appears comparable taking into account a small systematic
      difference between instruments.

PMID- 22458636
TI  - Regional variations in human patellar trabecular architecture and the structure
      of the quadriceps enthesis: a cadaveric study.
AB  - We investigated whether there were regional differences in the quadriceps
      enthesis and the patella bone structure that could suggest unequal force
      transmission to the patella. Quadriceps tendon enthesis was removed by cutting
      the patellae transversally in the middle and the quadriceps tendon approximately
      1 cm from the bone. Tissues were post-fixed, decalcified, dehydrated through and
      embedded in paraffin wax. Serial longitudinal sections were cut, mounted on glass
      slides at 1-mm intervals and slides were stained. Trabecular architecture was
      analysed from digital images taken from the histological slides, and regional
      differences at the enthesis in the thickness of the uncalcified fibrocartilage
      and the cortical zone of calcified tissue (calcified cartilage and lamellar bone)
      were evaluated. At the quadriceps enthesis, the thickness of the cortical zone of
      calcified tissue was significantly greater in the central part of the enthesis
      than medially and laterally. The trabeculae were thicker in the central and
      lateral parts compared with the medial region. Similarly, the zone of uncalcified
      fibrocartilage was thicker laterally and centrally than medially. Bone structure
      and the thickness of uncalcified fibrocartilage presented a similarity between
      the centre and the lateral parts; however, the medial side was different. We
      suggest that the mechanical stress at the proximal quadriceps tendon enthesis is
      higher laterally and centrally compared with medially. This could induce a
      lateral patellar translation, which is potentially a risk factor for knee
      osteoarthritis.

PMID- 22458637
TI  - Comparing culture, real-time PCR and fluorescence resonance energy transfer
      technology for detection of Porphyromonas gingivalis in patients with or without
      peri-implant infections.
AB  - BACKGROUND AND OBJECTIVE: The aim of the study was to compare the detection of
      Porphyromonas gingivalis using a fluorescence resonance energy transfer (FRET)
      technology with commonly used diagnostic methods in salivary and subgingival
      plaque samples from subjects with dental implants. P. gingivalis was considered
      as a marker for a pathogenic microbiota. MATERIAL AND METHODS: Ninety-seven adult
      subjects were recruited, including periodontally healthy controls with no dental
      implants, implant controls with no peri-implant disease and patients with peri
      implant disease. Saliva and subgingival/submucosal plaque samples were collected
      from all subjects and were analyzed using culture, real-time PCR and FRET
      technology employing P. gingivalis-specific substrates. RESULTS: It was found
      that the P. gingivalis-specific substrates were highly suitable for detecting the
      presence of P. gingivalis in saliva and in subgingival plaque samples, showing
      comparable specificity to culture and real-time PCR. CONCLUSION: We applied the
      FRET technology to detect P. gingivalis in implant patients with or without an
      implant condition and in controls without implants. The technique seems suitable
      for detection of P. gingivalis in both plaque and saliva samples. However, with
      all three techniques, P. gingivalis was not very specific for peri-implantitis
      cases. Future work includes fine-tuning the FRET technology and also includes the
      development of a chair-side application.

PMID- 22458638
TI  - A short-term double-blind randomized controlled pilot trial with active or
      placebo pindolol in patients treated with venlafaxine for major depression.
AB  - BACKGROUND: Pindolol has been widely investigated as an augmenter of
      antidepressant drug response. Results have been inconsistent. In this study, we
      used pindolol together with venlafaxine because of its ability to achieve a rapid
      onset of serotonin transporter blockade. AIMS: The object of this study was thus
      to investigate if pindolol augments the antidepressant response to venlafaxine.
      METHODS: Patients with major depression were randomized to either active or
      placebo pindolol 20 mg retard daily dosage and concomitantly treated with
      venlafaxine for 19 days. Depression severity was evaluated at four visits. Plasma
      concentrations of venlafaxine and its major metabolites O-desmethylvenlafaxine
      (ODV) and N-desmethylvenlafaxine (NDV) and pindolol were analysed. The ratio of
      ODV/venlafaxine was calculated. A low ratio corresponds to patients being poor
      metabolizers and a high ratio corresponds to patients being extensive
      metabolizers. RESULTS: No statistically significant difference in depression
      outcome was found between treatment groups. A statistically significant effect
      was, however, found of the ratio of ODV/venlafaxine on depression outcome,
      showing an augmenting effect of pindolol in patients with a low ratio, and the
      reverse in patients with a high ratio. CONCLUSION: The differential effect of
      pindolol, on depression outcome, in patients with varying degrees of venlafaxine
      metabolism into ODV, corresponds to patients being poor or extensive metabolizers
      of venlafaxine. From this finding, we conclude that only patients who are poor
      metabolizers of venlafaxine might benefit from pindolol augmentation. This
      mechanism might explain some of the variability of outcome in pindolol
      augmentation studies.

PMID- 22458639
TI  - Lapatinib, a dual inhibitor of epidermal growth factor receptor and human
      epidermal growth factor receptor 2, potentiates the antitumor effects of
      cisplatin on esophageal carcinoma.
AB  - Epidermal growth factor receptor (EGFR) and human epidermal growth factor
      receptor 2 (HER2) overexpression occurs in over 30% of esophageal carcinomas.
      Combination therapies of EGFR- and HER2-targeting agents with cytotoxic agents
      are considered a potential therapeutic strategy for esophageal cancer. The
      antitumor effects of lapatinib, a dual tyrosine kinase inhibitor of EGFR and
      HER2, cisplatin alone, and the combination of the two drugs on esophageal cancer
      cells were evaluated. The growth inhibition activity of lapatinib, cisplatin, and
      lapatinib plus cisplatin was measured by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di
      phenytetrazoliumromide (MTT) assays, and the combination index values were
      calculated. Additionally, cell cycle distribution and cell apoptosis treated with
      lapatinib or cisplatin alone and the combination of the two drugs were detected
      by flow cytometry analysis. The activation of EGFR and HER2 signaling pathways
      was monitored by Western blot analysis. These experimental data showed that the
      combination of lapatinib and cisplatin synergistically inhibited cell
      proliferation and exhibited an enhanced pro-apoptotic effect on esophageal cancer
      cells. The underlying mechanisms of potentiated effects of combined treatment
      were associated with reduced phosphorylation of EGFR and HER2, and the downstream
      signaling molecules AKT and extracellular regulated protein kinases (ERK). Our
      findings indicated that the combination of lapatinib and cisplatin is one of the
      promising treatment strategies for esophageal carcinomas with EGFR and HER2
      overexpression. 

PMID- 22458640
TI  - The use of videoconferencing to enhance interprofessional clinical education for
      allied health students.
AB  - The Health-e-Learning project investigated the use of videoconferencing to
      deliver interprofessional clinical education to allied health students. Via a
      broadband link, students observed DVD footage of a clinical session then
      participated in discussion with the clinicians at the Royal Children's Hospital
      (RCH), Melbourne. The videoconference sessions were evaluated with respect to
      session content, the effectiveness of videoconferencing in providing
      interprofessional education (IPE) and the satisfaction with this as a supplement
      to facility-based placements. During the two semesters of the project, 28
      videoconference sessions were conducted and 724 participants were surveyed.
      Student responses were positive with 84% indicating that these videoconferences
      increased their understanding of interprofessional practice (IPP) and 95%
      agreeing that the sessions were an effective learning tool. The results of this
      study support the use of videoconferencing to provide interprofessional clinical
      education.

PMID- 22458641
TI  - Virus variants with differences in the P1 protein coexist in a Plum pox virus
      population and display particular host-dependent pathogenicity features.
AB  - Subisolates segregated from an M-type Plum pox virus (PPV) isolate, PPV-PS,
      differ widely in pathogenicity despite their high degree of sequence similarity.
      A single amino acid substitution, K109E, in the helper component proteinase
      (HCPro) protein of PPV caused a significant enhancement of symptom severity in
      herbaceous hosts, and notably modified virus infectivity in peach seedlings. The
      presence of this substitution in certain subisolates that induced mild symptoms
      in herbaceous hosts and did not infect peach seedlings suggested the existence of
      uncharacterized attenuating factors in these subisolates. In this study, we show
      that two amino acid changes in the P1 protein are specifically associated with
      the mild pathogenicity exhibited by some PS subisolates. Site-directed
      mutagenesis studies demonstrated that both substitutions, W29R and V139E, but
      especially W29R, resulted in lower levels of virus accumulation and symptom
      severity in a woody host, Prunus persica. Furthermore, when W29R and V139E
      mutations were expressed concomitantly, PPV infectivity was completely abolished
      in this host. In contrast, the V139E substitution, but not W29R, was found to be
      responsible for symptom attenuation in herbaceous hosts. Deep sequencing analysis
      demonstrated that the W29R and V139E heterogeneities already existed in the
      original PPV-PS isolate before its segregation in different subisolates by local
      lesion cloning. These results highlight the potential complexity of potyviral
      populations and the relevance of the P1 protein of potyviruses in pathogenesis
      and viral adaptation to the host.

PMID- 22458642
TI  - In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol
      and a cardol enriched from Thai Apis mellifera propolis.
AB  - BACKGROUND: Propolis is a complex resinous honeybee product. It is reported to
      display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti
      tumor properties, which are mainly due to phenolic compounds, and especially
      flavonoids. The diversity of bioactive compounds depends on the geography and
      climate, since these factors affect the floral diversity. Here, Apis mellifera
      propolis from Nan province, Thailand, was evaluated for potential anti-cancer
      activity. METHODS: Propolis was sequentially extracted with methanol,
      dichloromethane and hexane and the cytotoxic activity of each crude extract was
      assayed for antiproliferative/cytotoxic activity in vitro against five human cell
      lines derived from duet carcinoma (BT474), undifferentiated lung (Chaco), liver
      hepatoblastoma (Hep-G(2)), gastric carcinoma (KATO-III) and colon adenocarcinoma
      (SW620) cancers. The human foreskin fibroblast cell line (Hs27) was used as a non
      transformed control. Those crude extracts that displayed
      antiproliferative/cytotoxic activity were then further fractionated by column
      chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection
      of the fractions. The chemical structure of each enriched bioactive compound was
      analyzed by nuclear magnetic resonance and mass spectroscopy. RESULTS: The crude
      hexane and dichloromethane extracts of propolis displayed
      antiproliferative/cytotoxic activities with IC(50) values across the five cancer
      cell lines ranging from 41.3 to 52.4 MUg/ml and from 43.8 to 53.5 MUg/ml,
      respectively. Two main bioactive components were isolated, one cardanol and one
      cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC(50)
      values across the five cancer cell lines and the control Hs27 cell line, ranging
      from 10.8 to 29.3 MUg/ml for the cardanol and < 3.13 to 5.97 MUg/ml (6.82 - 13.0
      MUM) for the cardol. Moreover, both compounds induced cytotoxicity and cell death
      without DNA fragmentation in the cancer cells, but only an antiproliferation
      response in the control Hs27 cells However, these two compounds did not account
      for the net antiproliferation/cytotoxic activity of the crude extracts suggesting
      the existence of other potent compounds or synergistic interactions in the
      propolis extracts. CONCLUSION: This is the first report that Thai A. mellifera
      propolis contains at least two potentially new compounds (a cardanol and a
      cardol) with potential anti-cancer bioactivity. Both could be alternative
      antiproliferative agents for future development as anti-cancer drugs.

PMID- 22458643
TI  - Single and multiple dose intravenous and oral pharmacokinetics of the hedgehog
      pathway inhibitor vismodegib in healthy female subjects.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: While recent publications have
      suggested the pharmacokinetics (PK) of vismodegib appear to be non-linear, there
      has not been a report describing the mechanisms of non-linearity. WHAT THIS STUDY
      ADDS: This study provides evidence that two separate processes, namely,
      solubility-limited absorption and concentration-dependent plasma protein binding,
      can explain the non-linear PK of vismodegib. This study provides quantitative
      results which can account for the lower than expected accumulation of vismodegib
      with continuous daily dosing. AIM: Vismodegib has demonstrated clinical activity
      in patients with advanced basal cell carcinoma. The pharmacokinetics (PK) of
      vismodegib are non-linear. The objective of this study was to determine whether
      vismodegib PK change following repeated dosing by administering a tracer
      intravenous (i.v.) dose of (14) C-vismodegib with single and multiple oral doses.
      METHODS: Healthy post menopausal female subjects (n= 6/group) received either a
      single or daily 150 mg vismodegib oral dose with a (14) C-labelled 10 ug i.v.
      bolus dose administered 2 h after the single or last oral dose (day 7). Plasma
      samples were assayed for vismodegib by LC-MS/MS and for (14) C-vismodegib by
      accelerator mass spectrometry. RESULTS: Following a single i.v. dose, mean
      clearance, volume of distribution and absolute bioavailability were 43.4 ml h(-1)
      , 16.4 l and 31.8%, respectively. Parallel concentration-time profiles following
      single oral and i.v. administration of vismodegib indicated elimination rate
      limited PK. Following i.v. administration at steady-state, mean clearance and
      volume of distribution were 78.5 ml h(-1) and 26.8 l, respectively. Comparison of
      i.v. PK parameters after single and multiple oral dosing showed similar half
      life, increased clearance and volume of distribution (81% and 63% higher,
      respectively) and decreased bioavailability (77% lower) after repeated dosing.
      Relative to single dose, the unbound fraction of vismodegib increased 2.4-fold
      with continuous daily dosing. CONCLUSION: Vismodegib exhibited a long terminal
      half-life after oral and i.v. administration, moderate absolute bioavailability
      and non-linear PK after repeated dosing. Results from this study suggest that the
      non-linear PK of vismodegib result from two separate, non-linear processes,
      namely solubility limited absorption and high affinity, saturable plasma protein
      binding.

PMID- 22458644
TI  - 3alpha-Hydroxymasticadienonic acid as an antiproliferative agent that impairs
      mitochondrial functions.
AB  - Previous investigations on the biological effects of 3alpha
      hydroxymasticadienonic acid (1) have demonstrated both anti-inflammatory and
      cytotoxic activities. However, neither the molecular mechanism of cytotoxic
      action nor the possible intracellular target(s) have been reported so far for
      this compound. The crucial role played by mitochondria on both cell survival and
      death, due to production of ATP and intrinsic apoptosis, respectively, prompted a
      study of the effect of 1 on isolated rat liver mitochondria. It was found that 1
      causes a dose-dependent impairment of mitochondrial bioenergetic parameters, such
      as the respiratory control index and transmembrane electrical potential.
      Moreover, in the presence of Ca(2+), at a 10 MUM concentration, 1 resulted in the
      induction of membrane permeability transition by oxidative stress, leading to the
      release of pro-apoptotic factors. At a 100 MUM concentration, compound 1 affected
      mitochondrial Ca(2+) transport by inhibiting the accumulation of the cation in
      the mitochondrial matrix. Altogether, it was demonstrated that 1 induces an
      impairment of mitochondrial functions that may account for the cytotoxicity
      exhibited by this compound.

PMID- 22458645
TI  - Utilization of insecticide treated nets during pregnancy among postpartum women
      in Ibadan, Nigeria: a cross-sectional study.
AB  - BACKGROUND: Pregnant women are susceptible to symptomatic malaria due to invasion
      of the placenta by plasmodium. Malaria increases the risk of adverse pregnancy
      outcomes for mothers, the foetuses and newborns. The effective use of Insecticide
      Treated Nets (ITNs) would be of benefit to these vulnerable women. Previous
      studies have focused on prenatal-women but this study sought to explore the
      actual trend of utilization of the proven strategy across all the pregnancy
      stages among postpartum women in Ibadan. METHODS: This cross-sectional survey
      utilized a validated structured questionnaire for data collection. A calculated
      sample of 335 postpartum women was proportionately recruited from three fee
      paying facilities within Ibadan, Nigeria using a simple random sampling
      technique. These hospitals have high client flow for maternity cases and are
      known for provision of care under traditional ANC model. The data collected were
      analyzed using descriptive and inferential statistics by means of Statistical
      Package of Social Sciences (SPSS) version 15. The level of significance was set
      at = 0.05. RESULTS: The women's age ranged between 18 and 47 years, mean age was
      29.4 +/- 0.8 years. Various irregularities marked the traditional model of ANC
      provided at the settings and no exposure to preconception care. Also, 276 (82.4%)
      had heard of ITNs. Antenatal clinics formed the major source of information. Low
      utilization and compliance rates were observed. One hundred and twenty-seven
      (37.9%) of the women had high knowledge of Malaria in Pregnancy (MIP) but only 70
      (20.9%) demonstrated positive attitude towards the use of ITNs. Participants'
      educational status, family types, employment and residential areas significantly
      influenced ITNs utilization. CONCLUSIONS: The women knew and learned about ITNs
      from ANC visits. Majority of the women did not own ITNs because of lack of access
      to free distribution. The existing traditional model of ANC was marked by
      irregularities and none of the women was exposed to preconception care. In
      addition, negative attitude in spite of increased knowledge of MIP was observed
      among the women. Therefore, evaluation of free distribution of ITNs is
      recommended. Integration of focused ANC and preconception care are advocated to
      promote early access to health information.

PMID- 22458647
TI  - Low-temperature preparation of tailored carbon nanostructures in water.
AB  - The development of low-temperature carbonization procedures promises to provide
      novel nanostructured carbon materials that are of high current interest in
      materials science and technology. Here, we report a "wet-chemical" carbonization
      method that utilizes hexayne amphiphiles as metastable carbon precursors. Nearly
      perfect control of the nanoscopic morphology was achieved by self-assembly of the
      precursors into colloidal aggregates with tailored diameter in water. Subsequent
      carbonization furnished carbon nanocapsules with a carbon microstructure
      resembling graphite-like amorphous carbon materials.

PMID- 22458646
TI  - Casein hydrolysate for uterine infection treatment: a patent evaluation
      (WO2011132191).
AB  - Metritis, endometritis and pyometra are common uterus inflammatory diseases,
      occurring mainly in the early postpartum period of livestock and farm animals.
      These infections are primarily associated with contamination of the reproductive
      tract, in particular uterine. Uterine infections bring to uterine and cervical
      involution as well as sub-fertility; the high economic loss, due to costs for
      treatment, milk withdrawal, reduced reproductive performance and premature
      culling, clearly demonstrate that uterine health in the postpartum period
      requires substantial medical veterinary attention. A wide variety of therapies
      for endometritis have been reported, including mainly antibiotics administered
      either by systemic or local somministration. Here, the patent application
      WO/2011/132191, which describes an alternative treatment for uterine infection,
      using casein peptides, is evaluated and discussed.

PMID- 22458648
TI  - Baclofen effects on alcohol seeking, self-administration and extinction of
      seeking responses in a within-session design in baboons.
AB  - Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under
      investigation as a potential treatment to prevent relapse to drinking in alcohol
      dependent persons. In the current study, two groups of baboons were trained under
      a chained schedule of reinforcement (CSR), with three linked components, which
      were each correlated with different response requirements and cues. Fulfilling
      the requirement in the second link initiated the third link where either alcohol
      (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for
      self-administration; failure to complete the response requirement in Link 2 ended
      the session (no access to alcohol or Tang). Seeking responses in Link 2 were used
      as indices of the motivational processes thought to be involved in relapse. The
      effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol
      or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg)
      significantly decreased (P < 0.05) alcohol self-administration responses and
      total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4
      mg/kg) reduced Tang self-administration and consumption. Under within-session
      extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of
      responding for both alcohol and Tang, particularly during the first 10 minutes of
      extinction. Baclofen may be effective in reducing craving and alcohol drinking,
      although the facilitation of extinction and suppression of both alcohol and Tang
      self-administration by baclofen suggests these effects may be related to a more
      general suppression of consummatory and conditioned behaviors.

PMID- 22458649
TI  - A one-year school-based diet/exercise intervention improves non-traditional
      disease biomarkers in Mexican-American children.
AB  - School-based interventions are an effective way to treat childhood obesity. The
      purpose of the present study was to biologically validate an established school
      based intervention designed to reduce standardised body mass index (zBMI) over a
      period of 12 months. This intervention focused on a subset of Mexican-American
      children who were participating in a larger clinical weight loss study. Plasma
      samples were analysed from self-identified Mexican-American children (12-14
      years) who were randomised to either a school-based intervention (IN, n = 152) or
      self-help control (CN, n = 69). Treatment was 4 days week-1 of exercise (45 min
      day-1) and 1 day week-1 of nutritional counselling for 6 months. Fasting (>8 h)
      blood samples were collected at baseline, 6 months (end of active intervention)
      and 12 months (6 months after the end of the active intervention). Plasma
      resistin, adiponectin and leptin concentration were measured using a multiplex
      assay. Separate linear mixed models and a P < 0.05 were used to test for
      significance. Significant group * time interactions were found for resistin (P <
      0.0001), adiponectin (P = 0.001) and leptin (P = 0.013). For resistin, IN was 12%
      lower at 6 months than CN. Adiponectin concentration in IN was greater at 6
      months (26%) and 12 months (8%) than CN. Leptin concentration was 22% lower for
      IN at 12 months than CN. We have previously reported that our school-based
      intervention reduced zBMI and now reported alterations in biologically relevant
      disease biomarkers. Some of the observed changes were only present at the end of
      the active intervention (resistin), while others persisted until 12 months
      (leptin and adiponectin). These changes underscore the effectiveness of our
      school-based intervention at not only improving zBMI but also at reducing disease
      risk.

PMID- 22458650
TI  - Topical valrubicin application reduces skin inflammation in murine models.
AB  - BACKGROUND: Valrubicin is a cytostatic anthracycline analogue, lacking toxicity
      by skin and tissue contact, and represents a new drug with potential for topical
      treatment of psoriasis and nonmelanoma skin cancer (NMSC); the beneficial effects
      have been partly explained by its antiproliferative and proapoptotic
      characteristics. OBJECTIVES: To assess the effect of valrubicin on skin
      inflammation as inflammation also plays a key role in psoriasis and NMSC.
      METHODS: The effect of topical valrubicin treatment on skin inflammation in vivo
      was addressed in skin inflammation mouse models, where 12-O-tetradecanoylphorbol
      13-acetate was used to induce irritant contact dermatitis. An acute and a chronic
      model were included, to investigate the effect of valrubicin in short-term
      inflammation and in more persistent inflammation. Inflammation-associated ear
      oedema was evaluated by measuring ear thickness, infiltration of neutrophil
      cells, and expression of inflammatory cytokines, interleukin (IL)-1beta and IL-6.
      RESULTS: Topical valrubicin treatment effectively reduced the inflammatory
      response in the acute and the chronic models. CONCLUSIONS: The present data
      document an anti-inflammatory effect of valrubicin, and may suggest an
      interesting new role for valrubicin in other debilitating skin diseases in which
      inflammation is a significant factor.

PMID- 22458651
TI  - Choroidal hemodynamic in myopic patients with and without primary open-angle
      glaucoma.
AB  - PURPOSE: To investigate the change in subfoveal choroidal blood flow in patients
      with glaucoma and to assess the effect of myopia, as one of the vascular risk
      factors for glaucoma on this flow. METHODS: Subfoveal choroidal blood flow in
      groups of 12 myopic and glaucomatous eyes has been investigated by means of the
      laser Doppler flowmetry (LDF), comparing the results with those of 17 myopic eyes
      without glaucoma, 34 non-myopic glaucomatous eyes and of 50 control eyes. The
      subfoveal choroidal LDF parameters, that is, blood velocity (ChBVel), volume
      (ChBVol), and flow (ChBF), as well as the vascular resistance were studied in
      each group. Statistical analysis was performed by means of anova and t-test
      according to the Bonferroni procedure for multiple comparisons. Pearson
      correlation was used to establish the correlations between the hemodynamic
      parameters and the degree of myopia in dioptres. RESULTS: All LDF parameters
      (ChBVel, ChBVol and ChBF) were significantly reduced in glaucomatous patients
      (1.3 +/- 0.4, 0.14 +/- 0.06 and 4 +/- 2 respectively) and myopic patients with
      primary open-angle glaucoma (POAG) (1.3 +/- 0.4, 0.08 +/- 0.04 and 2 +/- 0.7
      respectively) and without POAG (1.2 +/- 0.3, 0.11 +/- 0.08 and 2 +/- 1
      respectively) in comparison with age-matched controls (1.5 +/- 0.4, 0.27 +/- 0.1
      and 8 +/- 2 respectively). On the other hand, the choroidal vascular resistance
      (Rm) was increased in the previously described studied patients groups (16 +/- 7,
      26 +/- 9 and 24 +/- 9 respectively) compared with controls (7 +/- 2). The LDF
      parameters did not differ significantly between myopic subjects without and with
      POAG (p = 0.09, p = 0.09, p = 0.2, p = 0.08 and p = 0.9 respectively). Compared
      to patients with emmetropic glaucomatous, significant reduction in the ChBVol and
      ChBF and increased Rm were recorded in patients with glaucomatous myopia (p =
      0.05, p = 0.04 and p = 0.04 respectively). Pearson correlation demonstrated a
      significant correlation between the degree of myopia in dioptres and the ChBF (p
      = 0.012). CONCLUSIONS: The subfoveal choroidal LDF parameters were reduced in
      patients with POAG and myopia. Theses alterations are more in glaucomatous
      patients with myopia in comparison with age-matched glaucomatous patients without
      myopia. These data suggest that the impaired choroidal circulation caused by
      myopia might be an important additional risk factor involved in the glaucomatous
      damaging process.

PMID- 22458652
TI  - Three-dimensional super-localization and tracking of single gold nanoparticles in
      cells.
AB  - We introduce a precise three-dimensional (3D) localization method of spherical
      gold nanoparticle probes using model-based correlation coefficient mapping. To
      accomplish this, a stack of sample images at different z-positions are acquired,
      and a 3D intensity profile of the probe serving as the model is used to map out
      the positions of nanoparticles in the sample. By using this model-based
      correlation imaging method, precise localization can be achieved in imaging
      techniques with complicated point spread functions (PSF) such as differential
      interference contrast (DIC) microscopy. We demonstrated the localization
      precision of 4-7 nm laterally and 16 nm axially for 40-nm gold nanospheres at an
      imaging rate of 10 frames per second. The 3D superlocalization method was applied
      to tracking gold nanospheres during live endocytosis events.

PMID- 22458653
TI  - The sixth annual translational stem cell research conference of the New York Stem
      Cell Foundation.
AB  - The New York Stem Cell Foundation's "Sixth Annual Translational Stem Cell
      Research Conference" convened on October 11-12, 2011 at the Rockefeller
      University in New York City. Over 450 scientists, patient advocates, and stem
      cell research supporters from 14 countries registered for the conference. In
      addition to poster and platform presentations, the conference featured panels
      entitled "Road to the Clinic" and "The Future of Regenerative Medicine."

PMID- 22458655
TI  - The human hair follicle, a bistable organ?
AB  - The hair cycle and its control remain today an object of debate. A number of
      factors, which can modulate this process, have been identified but its
      choreography remains elusive. For years, the hunt for the conductor has been on,
      but nobody ever caught him. Intuitively, the process being considered as cyclic,
      an automaton controlling this cycle should be looked for, by analogy with a
      clock. However, the putative hair follicle oscillator that would control hair
      cycle failed to be identified and characterized. In fact, we have revealed that
      human hair follicle has an autonomous behaviour and that the transitions from one
      phase to the next occur independently for each follicle, after time intervals
      given stochastically by a lognormal distribution characterized by a mean and a
      variance. From this analysis, one can conclude that instead of a cyclical
      behaviour with an intrinsic automaton, a bistable steady state controls human
      hair follicle behaviour, which under a stochastic way jumps from the dormant to
      the active steady state and vice versa.

PMID- 22458654
TI  - Archaeal origin of tubulin.
AB  - Tubulins are a family of GTPases that are key components of the cytoskeleton in
      all eukaryotes and are distantly related to the FtsZ GTPase that is involved in
      cell division in most bacteria and many archaea. Among prokaryotes, bona fide
      tubulins have been identified only in bacteria of the genus Prosthecobacter.
      These bacterial tubulin genes appear to have been horizontally transferred from
      eukaryotes. Here we describe tubulins encoded in the genomes of thaumarchaeota of
      the genus Nitrosoarchaeum that we denote artubulins Phylogenetic analysis results
      are compatible with the origin of eukaryotic tubulins from artubulins. These
      findings expand the emerging picture of the origin of key components of
      eukaryotic functional systems from ancestral forms that are scattered among the
      extant archaea.

PMID- 22458656
TI  - Substrate and enzyme functional groups contribute to translational quality
      control by bacterial prolyl-tRNA synthetase.
AB  - Aminoacyl-tRNA synthetases activate specific amino acid substrates and attach
      them via an ester linkage to cognate tRNA molecules. In addition to cognate
      proline, prolyl-tRNA synthetase (ProRS) can activate cysteine and alanine and
      misacylate tRNA(Pro). Editing of the misacylated aminoacyl-tRNA is required for
      error-free protein synthesis. An editing domain (INS) appended to bacterial ProRS
      selectively hydrolyzes Ala-tRNA(Pro), whereas Cys-tRNA(Pro) is cleared by a
      freestanding editing domain, YbaK, through a unique mechanism involving substrate
      sulfhydryl chemistry. The detailed mechanism of catalysis by INS is currently
      unknown. To understand the alanine specificity and mechanism of catalysis by INS,
      we have explored several possible mechanisms of Ala-tRNA(Pro) deacylation via
      hybrid QM/MM calculations. Experimental studies were also performed to test the
      role of several residues in the INS active site as well as various substrate
      functional groups in catalysis. Our results support a critical role for the tRNA
      2'-OH group in substrate binding and catalytic water activation. A role is also
      proposed for the protein's conserved GXXXP loop in transition state stabilization
      and for the main chain atoms of Gly261 in a proton relay that contributes
      substantially to catalysis.

PMID- 22458659
TI  - Nutrient limitation on terrestrial plant growth--modeling the interaction between
      nitrogen and phosphorus.
AB  - Growth of plants in terrestrial ecosystems is often limited by the availability
      of nitrogen (N) or phosphorous (P) Liebig's law of the minimum states that the
      nutrient in least supply relative to the plant's requirement will limit the
      plant's growth. An alternative to the law of the minimum is the multiple
      limitation hypothesis (MLH) which states that plants adjust their growth patterns
      such that they are limited by several resources simultaneously. We use a simple
      model of plant growth and nutrient uptake to explore the consequences for the
      plant's relative growth rate of letting plants invest differentially in N and P
      uptake. We find a smooth transition between limiting elements, in contrast to the
      strict transition in Liebig's law of the minimum. At N : P supply ratios where
      the two elements simultaneously limit growth, an increase in either of the
      nutrients will increase the growth rate because more resources can be allocated
      towards the limiting element, as suggested by the multiple limitation hypothesis.
      However, the further the supply ratio deviates from these supply rates, the more
      the plants will follow the law of the minimum. Liebig's law of the minimum will
      in many cases be a useful first-order approximation.

PMID- 22458657
TI  - Alterations in intermediate filaments expression in disc cells from the rat
      temporomandibular joint following exposure to continuous compressive force.
AB  - The articular disc in the temporomandibular joint (TMJ) that serves in load
      relief and stabilizing in jaw movements is a dense collagenous tissue consisting
      of extracellular matrices and disc cells. The various morphological
      configurations of the disc cells have given us diverse names, such as
      fibroblasts, chondrocyte-like cells and fibrochondrocytes; however, the
      characteristics of these cells have remained to be elucidated in detail. The disc
      cells have been reported to exhibit heterogeneous immunoreaction patterns for
      intermediate filaments including glial fibrillary acidic protein (GFAP), nestin
      and vimentin in the adult rat TMJ. Because these intermediate filaments
      accumulate in the disc cells as tooth eruption proceeds during postnatal
      development, it might be surmised that the expression of these intermediate
      filaments in the disc cells closely relates to mechanical stress. The present
      study was therefore undertaken to examine the effect of a continuous compressive
      force on the immunoexpression of these intermediate filaments and an additional
      intermediate filament - muscle-specific desmin - in the disc cells of the TMJ
      disc using a rat experimental model. The rats wore an appliance that exerts a
      continuous compressive load on the TMJ. The experimental period with the
      appliance was 5 days as determined by previous studies, after which some
      experimental animals were allowed to survive another 5 days after removal of the
      appliance. Histological observations demonstrated that the compressive force
      provoked a remarkable acellular region and a decrease in the thickness of the
      condylar cartilage of the mandible, and a sparse collagen fiber distribution in
      the articular disc. The articular disc showed a significant increase in the
      number of desmin-positive cells as compared with the controls. In contrast,
      immunopositive cells for GFAP, nestin and vimentin remained unchanged in number
      as well as intensity. At 5 days after removal of the appliance, both the disc and
      cartilage exhibited immunohistological and histological features in a recovery
      process. These findings indicate that the mature articular cells are capable of
      producing desmin instead of the other intermediate filaments against mechanical
      stress. The desmin-positive disc cells lacked alpha-smooth muscle actin (alpha
      SMA) in this study, even though desmin usually co-exists with alpha-SMA in the
      vascular smooth muscle cells or pericytes. Because the precursor of a pericyte
      has such an immunoexpression pattern during angiogenesis, there is a further
      possibility that the formation of new vessels commenced in response to the
      extraordinary compressive force.

PMID- 22458660
TI  - Interferential therapy effect on mechanical pain threshold and isometric torque
      after delayed onset muscle soreness induction in human hamstrings.
AB  - This study was undertaken to examine the acute effect of interferential current
      on mechanical pain threshold and isometric peak torque after delayed onset muscle
      soreness induction in human hamstrings. Forty-one physically active healthy male
      volunteers aged 18-33 years were randomly assigned to one of two experimental
      groups: interferential current group (n = 21) or placebo group (n = 20). Both
      groups performed a bout of 100 isokinetic eccentric maximal voluntary
      contractions (10 sets of 10 repetitions) at an angular velocity of 1.05 rad . s(
      1) (60 degrees  . s(-1)) to induce muscle soreness. On the next day, volunteers
      received either an interferential current or a placebo application. Treatment was
      applied for 30 minutes (4 kHz frequency; 125 MUs pulse duration; 80-150 Hz
      bursts). Mechanical pain threshold and isometric peak torque were measured at
      four different time intervals: prior to induction of muscle soreness, immediately
      following muscle soreness induction, on the next day after muscle soreness
      induction, and immediately after the interferential current and placebo
      application. Both groups showed a reduction in isometric torque (P < 0.001) and
      pain threshold (P < 0.001) after the eccentric exercise. After treatment, only
      the interferential current group showed a significant increase in pain threshold
      (P = 0.002) with no changes in isometric torque. The results indicate that
      interferential current was effective in increasing hamstrings mechanical pain
      threshold after eccentric exercise, with no effect on isometric peak torque after
      treatment.

PMID- 22458661
TI  - Digestive disease week 2011: highlights of clinical and preclinical research on
      Barrett's esophagus and associated esophageal adenocarcinoma.
AB  - Clinicians and basic researchers worldwide convened at the annual Digestive
      Disease Week where the latest research in the field of gastroenterology and
      hepatology is presented. In this report, the highlights of the convention on the
      field of Barrett's esophagus (BE) and associated esophageal adenocarcinoma (EAC)
      are summarized. New clinical and preclinical developments in etiology, diagnosis,
      surveillance, and prevention and therapy of BE and EAC in respect to current
      knowledge are reflected. We also discuss the relevance and impact of these
      findings on the future of BE and EAC research.

PMID- 22458662
TI  - Dermoscopic assessment for a brushing treatment for a patient pelted with metal
      fragments in an industrial explosion.

PMID- 22458664
TI  - Oxidative dimerization of (E)- and (Z)-2-propenylsesamol with O2 in the presence
      and absence of laccases and other catalysts: selective formation of carpanones
      and benzopyrans under different reaction conditions.
AB  - The oxidative dimerization of 2-propenylsesamol to carpanone with O(2) as the
      oxidant, which probably proceeds as a domino phenol oxidation/anti-beta,beta
      radical coupling/intramolecular hetero Diels-Alder reaction, can be efficiently
      catalyzed by laccases. Experiments with laccases and other catalysts like a
      Co(salen) type catalyst and PdCl(2) clearly demonstrate that the
      diastereoselectivity of the carpanone formation does not depend on the catalyst
      but on the double-bond geometry of the substrate. With (E)-2-propenylsesamol as
      the substrate, carpanone and a so far unknown carpanone diastereoisomer are
      formed in a 9:1 ratio. When (Z)-2-propenylsesamol is used as starting material,
      carpanone is accompanied by two carpanone diastereoisomers unknown so far in a
      5:1:4 ratio. All three carpanone diastereoisomers have been separated by HPLC,
      and their structures have been elucidated unambiguously by NMR spectroscopy, DFT
      calculations, and spin work analysis. When the oxidation of 2-propenylsesamol
      with O(2) is performed in the absence of any catalyst two diastereoisomeric
      benzopyrans are formed, probably as the result of a domino
      oxidation/intermolecular hetero Diels-Alder reaction. Under these conditions,
      carpanone is formed in trace amounts only.

PMID- 22458666
TI  - Fe-haem bound to Escherichia coli bacterioferritin accelerates iron core
      formation by an electron transfer mechanism.
AB  - BFR (bacterioferritin) is an iron storage and detoxification protein that differs
      from other ferritins by its ability to bind haem cofactors. Haem bound to BFR is
      believed to be involved in iron release and was previously thought not to play a
      role in iron core formation. Investigation of the effect of bound haem on
      formation of the iron core has been enabled in the present work by development of
      a method for reconstitution of BFR from Escherichia coli with exogenously added
      haem at elevated temperature in the presence of a relatively high concentration
      of sodium chloride. Kinetic analysis of iron oxidation by E. coli BFR
      preparations containing various amounts of haem revealed that haem bound to BFR
      decreases the rate of iron oxidation at the dinuclear iron ferroxidase sites but
      increases the rate of iron core formation. Similar kinetic analysis of BFR
      reconstituted with cobalt-haem revealed that this haem derivative has no
      influence on the rate of iron core formation. These observations argue that haem
      bound to E. coli BFR accelerates iron core formation by an electron-transfer
      based mechanism.

PMID- 22458665
TI  - HERALD (health economics using routine anonymised linked data).
AB  - BACKGROUND: Health economic analysis traditionally relies on patient derived
      questionnaire data, routine datasets, and outcomes data from experimental
      randomised control trials and other clinical studies, which are generally used as
      stand-alone datasets. Herein, we outline the potential implications of linking
      these datasets to give one single joined up data-resource for health economic
      analysis. METHOD: The linkage of individual level data from questionnaires with
      routinely-captured health care data allows the entire patient journey to be
      mapped both retrospectively and prospectively. We illustrate this with examples
      from an Ankylosing Spondylitis (AS) cohort by linking patient reported study
      dataset with the routinely collected general practitioner (GP) data, inpatient
      (IP) and outpatient (OP) datasets, and Accident and Emergency department data in
      Wales. The linked data system allows: (1) retrospective and prospective tracking
      of patient pathways through multiple healthcare facilities; (2) validation and
      clarification of patient-reported recall data, complementing the
      questionnaire/routine data information; (3) obtaining objective measure of the
      costs of chronic conditions for a longer time horizon, and during the pre
      diagnosis period; (4) assessment of health service usage, referral histories,
      prescribed drugs and co-morbidities; and (5) profiling and stratification of
      patients relating to disease manifestation, lifestyles, co-morbidities, and
      associated costs. RESULTS: Using the GP data system we tracked about 183 AS
      patients retrospectively and prospectively from the date of questionnaire
      completion to gather the following information: (a) number of GP events; (b)
      presence of a GP 'drug' read codes; and (c) the presence of a GP 'diagnostic'
      read codes. We tracked 236 and 296 AS patients through the OP and IP data systems
      respectively to count the number of OP visits; and IP admissions and duration.
      The results are presented under several patient stratification schemes based on
      disease severity, functions, age, sex, and the onset of disease symptoms.
      CONCLUSION: The linked data system offers unique opportunities for enhanced
      longitudinal health economic analysis not possible through the use of traditional
      isolated datasets. Additionally, this data linkage provides important information
      to improve diagnostic and referral pathways, and thus helps maximise clinical
      efficiency and efficiency in the use of resources.

PMID- 22458667
TI  - Morphological differentiation of severe aplastic anaemia from hypocellular
      refractory cytopenia of childhood: reproducibility of histopathological
      diagnostic criteria.
AB  - AIMS: To evaluate the reproducibility and reliability of the histomorphological
      criteria differentiating severe aplastic anaemia (SAA) and hypoplastic refractory
      cytopenia of childhood (RCC), the most frequently acquired hypocellular bone
      marrow conditions of childhood. METHODS AND RESULTS: We performed a double-blind
      interobserver study of 100 different cases of SAA and RCC among seven
      haematopathologists of the European Working Group of MDS in Childhood (EWOG-MDS)
      and the German SAA study. Cases with foci of typical myelodysplastic syndrome
      (MDS) morphology, such as patchy erythropoiesis with defective maturation, in an
      otherwise highly hypocellular or adipocytic bone marrow were classified as having
      RCC. Bone marrow samples without a patchy distribution, few scattered myeloid
      cells or haematopoietic aplasia were diagnosed as SAA. In only four of 100 cases
      did the reference pathologists not reach agreement regarding classification as
      SAA or RCC. The kappa index was 0.79. CONCLUSIONS: Our results show that the vast
      majority of SAA and RCC cases can be reliably differentiated by morphological
      means alone. A clear differentiation between SAA and RCC at presentation is
      mandatory for optimizing therapy strategies, and might be responsible for the
      fact that, in the German childhood SAA study, the probability of developing
      clonal disease after immunosuppressive therapy has dropped to 3%.

PMID- 22458668
TI  - Physical inactivity in aging and dementia: a review of its relationship to pain.
AB  - AIMS: The goal of this brief review is to address studies examining the
      relationship between physical inactivity and pain in aging and dementia.
      BACKGROUND: A decrease in the level of physical activity is characteristic of
      older persons, both with and without dementia. Passive behaviour is often
      considered to be part of the apathy frequently observed in patients with
      dementia, although it could also be a sign of pain. Design.  Literature review.
      Method.  Searches were performed in PubMed and Embase. A total of 15 studies
      concerning the relationship between physical inactivity and pain in older persons
      with and without dementia were identified (older persons without dementia: 12;
      with dementia: 3). RESULTS: In older persons without dementia, a positive
      relationship between physical inactivity and pain has been demonstrated. In older
      persons with dementia, pain may cause physical inactivity and physical inactivity
      may cause pain. Conclusions.  In older persons, a positive relationship between
      physical inactivity and pain was demonstrated. More specifically, pain may cause
      physical inactivity. In older persons with dementia pain may cause physical
      inactivity and vice versa. RELEVANCE TO CLINICAL PRACTICE: Nurses' awareness of
      physical inactivity as an indication of pain in older persons with and without
      dementia may reduce the risk of underdiagnosis and subsequent undertreatment of
      pain.

PMID- 22458669
TI  - Inhibition of tumor cells interacting with stromal cells by xanthones isolated
      from a Costa Rican Penicillium sp.
AB  - CR1642D, an endophytic isolate of Penicillium sp. collected from a Costa Rican
      rainforest, was identified through a high-throughput approach to identify natural
      products with enhanced antitumor activity in the context of tumor-stromal
      interactions. Bioassay-guided separation led to the identification of five
      xanthones (1-5) from CR1642D. The structures of the xanthone dimer penexanthone A
      (1) and monomer penexanthone B (2) were elucidated on the basis of spectroscopic
      analyses, including 2D NMR experiments. All of the compounds were tested against
      a panel of tumor cell lines in the presence and absence of bone marrow stromal
      cells. Compound 3 was the most active, with IC(50) values of 1-17 MUM, and its
      activity was enhanced 2-fold against tumor cell line RPMI8226 in the presence of
      stromal cells (IC(50) 1.2 MUM, but 2.4 MUM without stromal cells).

PMID- 22458670
TI  - Highly enantioselective synthesis of 2,3-dihydroquinazolinones through
      intramolecular amidation of imines.
AB  - Enantioselective synthesis of 2,3-dihydroquinazolinones (DHQZs) was accomplished
      using readily available Sc(III)-inda-pybox as the catalyst. This is the first
      report on the metal catalyzed asymmetric intramolecular amidation of imines to
      synthesize DHQZs.

PMID- 22458671
TI  - The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal
      necrolysis: a systematic review and meta-analysis.
AB  - BACKGROUND: Quantitative analysis of intravenous immunoglobulin (IVIg) treatment
      against toxic epidermal necrolysis (TEN) is lacking. OBJECTIVES: To provide a
      meta-analysis evidence-based examination of IVIg efficacy against TEN. METHODS: A
      systematic review and meta-analysis of literature published before 31 July 2011
      was conducted. In observational controlled studies with at least eight patients
      with TEN receiving IVIg treatment, a pooled estimate of mortality risk was
      determined, comparing IVIg and supportive care. Statistical analyses were
      performed on raw data to compare the clinical differences between (i) high-dose
      and low-dose IVIg treatment in adult patients and (ii) paediatric and adult
      patients treated with IVIg. RESULTS: Seventeen studies met inclusion criteria.
      Overall mortality rate of patients with TEN treated with IVIg was 19.9%. The
      pooled odds ratio (OR) for mortality from six observational controlled studies
      comparing IVIg and supportive care was 1.00 [95% confidence interval (CI) 0.58
      1.75; P=0.99]. The pooled OR for mortality in patients treated with high-dose
      IVIg vs. supportive care was 0.63 (95% CI 0.27-1.44; P=0.27). Adults treated with
      high-dose IVIg exhibited significantly lower mortality than those treated with
      low-dose IVIg (18.9% vs. 50%, respectively; P=0.022); however, multivariate
      logistic regression model adjustment indicated that IVIg dose does not correlate
      with mortality (high vs. low dose: OR 0.494; 95% CI 0.106-2.300; P=0.369).
      Paediatric patients treated with IVIg had significantly lower mortality than
      adults (0% vs. 21.6%; P=0.001). CONCLUSIONS: Although high-dose IVIg exhibited a
      trend towards improved mortality and children treated with IVIg had a good
      prognosis, the evidence does not support a clinical benefit of IVIg. Randomized
      controlled trials are necessary.

PMID- 22458672
TI  - History of the International Society for Diseases of the Esophagus.

PMID- 22458673
TI  - Ultrafast kinetic DNA hybridization assay based on the visualization of threshold
      turbidity.
AB  - We report herein the development of an ultrafast kinetic DNA hybridization assay
      system based on the visualization of threshold turbidity associated with the
      assembly of polystyrene nanospheres. Initial testing of our diagnostic protocol
      on a sequence associated with the anthrax lethal factor indicates that a visually
      identifiable, turbidity-definitive, and kinetic threshold state could be reached
      at a time as short as 1 min. The assay scheme allows for both target
      concentration quantification and differentiation of single base mismatches
      through registry of the threshold turbidity onset time. The positively charged
      environment on nanospheres not only contributes to expedited signal generation
      but also imparts cooperative DNA binding properties. The kinetic visual protocol
      complements conventionally used thermodynamic strategies and provides an entry
      point for the circumvention of assay issues associated with ill-defined
      thermodynamic end points.

PMID- 22458674
TI  - Optimization of model parameters for describing the amide I spectrum of a large
      set of proteins.
AB  - A new simulation protocol for the prediction of the infrared absorption of the
      amide I vibration of proteins was developed. The method incorporates known
      effects on the intrinsic frequencies (backbone conformation, interpeptide and
      peptide-solvent hydrogen bonding) and couplings (nearest neighbor coupling,
      transition dipole coupling) of amide I oscillators in a parametrized manner.
      Model parameters for the simulation of amide I spectra were determined through
      fitting and optimization of simulated spectra to experimentally measured infrared
      spectra of 44 proteins that represent maximum structural variation in terms of
      different folds and secondary structure contents. Prediction of protein spectra
      using the optimized parameters resulted in good agreement with experimental
      spectra and in a considerable improvement compared to a description involving
      only transition dipole coupling. 

PMID- 22458675
TI  - Increased serum baseline tryptase levels and extensive skin involvement are
      predictors for the severity of mast cell activation episodes in children with
      mastocytosis.
AB  - BACKGROUND: Despite the good prognosis of pediatric mastocytosis, some patients
      suffer from severe mast cell (MC) mediator-associated symptoms. The aim of this
      study was to identify predictors for severe MC mediator release symptoms in
      children with mastocytosis in the skin (MIS). METHODS: Serum baseline total
      tryptase (sbT) levels in 111 children with MIS - 80 maculopapular cutaneous
      mastocytosis/plaque mastocytosis, 22 nodular mastocytosis, and nine diffuse
      cutaneous mastocytosis - were investigated as a predictive biomarker for the
      occurrence of MC mediator-related signs and symptoms within the first 18 months
      after disease onset. RESULTS: Twelve children (11%) who showed extensive
      cutaneous disease involving >90% of body surface area (BSA) suffered from severe
      symptoms requiring hospitalization, with (n = 5) or without (n = 6) management in
      the intensive care unit (ICU) owing to life-threatening complications. The median
      sbT was significantly (P < 0.001) higher in patients with extensive cutaneous
      disease vs those with <90% of BSA involved (45.5 vs 5.2 MUg/l, respectively), as
      well as in children with grade 4 (severe mastocytosis-related symptoms requiring
      emergency therapy and hospitalization) vs those with grade <4 (46.2 vs 5.2 MUg/l,
      respectively). Receiver operating characteristics curve analyses showed that the
      optimal cutoff s for sbT to predict the need for daily antimediator therapy,
      hospitalization, and the management in an ICU were 6.6, 15.5, and 30.8 MUg/l,
      respectively (sensitivity and specificity of 77% and 79%, 100% and 95%, and 100%
      and 96%, respectively). CONCLUSIONS: Increased sbT in association with extensive
      cutaneous involvement identifies patients at risk for severe MC activation events
      in pediatric mastocytosis.

PMID- 22458677
TI  - Nuclear receptors as pharmaceutical targets: rise of FXR and rebirth of PPAR?

PMID- 22458676
TI  - Volitional reduction of anterior cingulate cortex activity produces decreased cue
      craving in smoking cessation: a preliminary real-time fMRI study.
AB  - Numerous research groups are now using analysis of blood oxygen level-dependent
      (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back
      information about regional activity in their brains to participants in the
      scanner in 'real time'. In this study, we explored the feasibility of self
      regulation of frontal cortical activation using real-time fMRI (rtfMRI)
      neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking
      cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla
      MRI scanner to induce their nicotine craving. Participants were instructed to
      modify their craving using rtfMRI feedback with two different approaches. In a
      'reduce craving' paradigm, participants were instructed to 'reduce' their
      craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate
      'increase resistance' paradigm, participants were asked to increase their
      resistance to craving and to increase middle prefrontal cortex (mPFC) activity.
      We found that participants were able to significantly reduce the BOLD signal in
      the ACC during the 'reduce craving' task (P=0.028). There was a significant
      correlation between decreased ACC activation and reduced craving ratings during
      the 'reduce craving' session (P=0.011). In contrast, there was no modulation of
      the BOLD signal in mPFC during the 'increase resistance' session. These
      preliminary results suggest that some smokers may be able to use neurofeedback
      via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking
      cue-induced craving. Further research is needed to determine the optimal
      parameters of neurofeedback rtfMRI, and whether it might eventually become a
      therapeutic tool for nicotine dependence.

PMID- 22458679
TI  - Virtual compound screening in drug discovery.
AB  - Virtual screening (VS) methods are applied in both academia and drug discovery,
      and can be divided into ligand- and target structure-based approaches. The VS
      field is still evolving and is characterized by scientific heterogeneity. The
      value of virtual compound screening for drug discovery is often debated, in
      particular, given the large investments made in experimental high-throughput
      screening technologies. The current state-of-the-art in the VS field is
      discussed. Despite its limitations, VS applications have often succeeded in
      identifying novel hits including first-in-class active compounds and novel
      chemotypes. VS has its place in pharmaceutical research, but there is still much
      room for further improvements including method evaluation and drug discovery
      applications. The potential of VS is currently underutilized because its
      complementarity to high-throughput screening is not sufficiently exploited.
      Building close interfaces between computational and experimental screening would
      further streamline the hit identification process.

PMID- 22458680
TI  - Analysis of structure-based virtual screening studies and characterization of
      identified active compounds.
AB  - Structure-based virtual screening makes explicit or implicit use of 3D target
      structure information to detect novel active compounds. Results of nearly 300
      currently available original applications have been analyzed to characterize the
      state-of-the-art in this field. Compound selection from docking calculations is
      much influenced by subjective criteria. Although submicromolar compounds are
      identified, the majority of docking hits are only weakly potent. However, only a
      small percentage of docking hits can be reproduced by ligand-based methods. When
      docking calculations identify potent hits, they often originate from specialized
      compound sources (e.g., pharmaceutical compound decks or target-focused
      libraries) and also display a notable bias towards kinase targets. Structure
      based virtual screening is the dominant approach to computational hit
      identification. Docking calculations frequently identify active compounds.
      Limited accuracy of compound scoring and ranking currently presents a major
      caveat of the approach that is often compensated for by chemical intuition and
      knowledge.

PMID- 22458681
TI  - Hematopoietic, CNS and skeletal muscle stem cells as drug targets: opportunities,
      progress and challenges.
AB  - Lineage-committed stem and progenitor cells are currently targeted by a handful
      of medicines, mainly to treat conditions involving the immune and hematopoietic
      systems. Knowledge of new stem and progenitor cell populations in the body is
      accumulating at a rapid pace and a new era of targeting resident stem cell
      populations for therapeutic ends is coming into focus. Small-molecule regulators
      of body-resident stem and progenitor cell assess are now a reality both in the
      clinic and as promising new drugs in the development pipeline. This review will
      explore the current state of the art with an emphasis on emerging concepts and
      experimental systems in the therapeutic regulation of endogenous stem and
      progenitor cell populations.

PMID- 22458682
TI  - Progress in the development of anti-hepatitis C virus nucleoside and nucleotide
      prodrugs.
AB  - The search for new anti-hepatitis C virus (HCV) therapeutics continues as the
      current treatment, consisting of PEGylated IFN-alpha and ribavirin, is of limited
      efficacy, nonspecific and can cause significant side effects. Modified nucleoside
      analogues with improved efficacy and selectivity, may become the backbone of the
      future standard of care for anti-HCV therapies. Several families of modified
      nucleoside are known to inhibit HCV RNA-dependent RNA polymerase, a vital enzyme
      for viral replication. Ongoing efforts are focused on improvement of potency,
      selectivity and delivery of antiviral nucleoside analogues, with several recent
      promising advances into clinical trials. This review summarizes the current
      progress in the development of new anti-HCV nucleoside and nucleotide prodrugs.

PMID- 22458683
TI  - Neutrophil elastase inhibitors: recent advances in the development of mechanism
      based and nonelectrophilic inhibitors.
AB  - Due to its implication in pathologies of prevalent diseases such as chronic
      obstructive pulmonary disease, fibrosis, bronchiectasis and ARDS, the serine
      protease, human neutrophil elastase, has been in focus for drug-development
      efforts over the last two decades. In recent years, continued efforts to identify
      and optimize novel mechanism-based inhibitors have led to a number of new
      inhibitors being reported. These compounds show promising potency and selectivity
      profiles, although their use is still limited by their inherent stability.
      Recently, two novel classes of potent and selective, synthetic, nonelectrophilic
      human neutrophil elastase inhibitors that display improved stability and overall
      drug-like properties have been reported. The most advanced compound from these
      classes, AZD9668, has been reported to show significant effects on relevant
      biomarkers in bronchiectasis and cystic fibrosis patient populations.

PMID- 22458684
TI  - Ion channel drug discovery: challenges and future directions.
AB  - Ion channels are targets of many therapeutically useful agents, and worldwide
      sales of ion channel-targeted drugs are estimated to be approximately US$12
      billion. Nevertheless, considering that over 400 genes encoding ion channel
      subunits have been identified, ion channels remain significantly under-exploited
      as therapeutic targets. This is at least partly due to limitations in high
      throughput assay technologies that support screening and lead optimization. Will
      the recent developments in automated electrophysiology rectify this situation?
      What are the other major limitations and can they be overcome? In this article,
      we review the status of ion channel drug discovery, discuss current challenges
      and propose alternative approaches that may facilitate the discovery of new drugs
      in the future.

PMID- 22458685
TI  - Use of physiologically based pharmacokinetic modeling for assessment of drug-drug
      interactions.
AB  - Interactions between co-administered medicines can reduce efficacy or lead to
      adverse effects. Understanding and managing such interactions is essential in
      bringing safe and effective medicines to the market. Ideally, interaction
      potential should be recognized early and minimized in compounds that reach late
      stages of drug development. Physiologically based pharmacokinetic models combine
      knowledge of physiological factors with compound-specific properties to simulate
      how a drug behaves in the human body. These software tools are increasingly used
      during drug discovery and development and, when integrating relevant in vitro
      data, can simulate drug interaction potential. This article provides some
      background and presents illustrative examples. Physiologically based models are
      an integral tool in the discovery and development of drugs, and can significantly
      aid our understanding and prediction of drug interactions.

PMID- 22458688
TI  - The novel virulence-related gene nlxA in the lipopolysaccharide cluster of
      Xanthomonas citri ssp. citri is involved in the production of lipopolysaccharide
      and extracellular polysaccharide, motility, biofilm formation and stress
      resistance.
AB  - Lipopolysaccharide (LPS) is an important virulence factor of Xanthomonas citri
      ssp. citri, the causative agent of citrus canker disease. In this research, a
      novel gene, designated as nlxA (novel LPS cluster gene of X. citri ssp. citri),
      in the LPS cluster of X. citri ssp. citri 306, was characterized. Our results
      indicate that nlxA is required for O-polysaccharide biosynthesis by encoding a
      putative rhamnosyltransferase. This is supported by several lines of evidence:
      (i) NlxA shares 40.14% identity with WsaF, which acts as a rhamnosyltransferase;
      (ii) sodium dodecylsulphate-polyacrylamide gel electrophoresis analysis showed
      that four bands of the O-antigen part of LPS were missing in the LPS production
      of the nlxA mutant; this is also consistent with a previous report that the O
      antigen moiety of LPS of X. citri ssp. citri is composed of a rhamnose homo
      oligosaccharide; (iii) mutation of nlxA resulted in a significant reduction in
      the resistance of X. citri ssp. citri to different stresses, including sodium
      dodecylsulphate, polymyxin B, H(2)O(2), phenol, CuSO(4) and ZnSO(4). In addition,
      our results indicate that nlxA plays an important role in extracellular
      polysaccharide production, biofilm formation, stress resistance, motility on semi
      solid plates, virulence and in planta growth in the host plant grapefruit.

PMID- 22458687
TI  - Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt
      pathway in LPS-induced acute lung injury.
AB  - BACKGROUND: Stimulation of epithelial sodium channel (ENaC) increases Na(+)
      transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar
      spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is
      well recognized that regulation of ENaC by insulin via PI3K pathway, but the
      mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains
      unclear. The aim of this study was to investigate the effect of insulin on AFC in
      ALI and clarify the pathway in which insulin regulates the expression of ENaC in
      vitro and in vivo. METHODS: A model of ALI (LPS at a dose of 5.0 mg/kg) with non
      hyperglycemia was established in Sprague-Dawley rats receiving continuous
      exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated
      for measurement of bronchoalveolar lavage fluid(BALF), total lung water
      content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells
      were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes
      before insulin treatment for 2 hours. The expressions of alpha-,beta-, and gamma
      ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain
      reaction (RT-PCR) and western blotting. RESULTS: In vivo, insulin decreased TLW,
      enchanced AFC, increased the expressions of alpha-,beta-, and gamma-ENaC and the
      level of phosphorylated Akt, attenuated lung injury and improved the survival
      rate in LPS-induced ALI, the effects of which were blocked by wortmannin.
      Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced
      increase in AFC. In vitro, insulin increased the expressions of alpha-,beta-, and
      gamma-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt
      inhibitor significantly prevented insulin-induced increase in the expression of
      ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation
      studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin
      via PI3K/Akt pathway. CONCLUSIONS: Our study demonstrated that insulin alleviated
      pulmonary edema and enhanced AFC by increasing the expression of ENaC that
      dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.

PMID- 22458689
TI  - Stereoselectivities of histidine-catalyzed asymmetric aldol additions and
      contrasts with proline catalysis: a quantum mechanical analysis.
AB  - Quantum mechanical calculations reveal the origin of diastereo- and
      enantioselectivities of aldol reactions between aldehydes catalyzed by histidine,
      and differences between related reactions catalyzed by proline. A stereochemical
      model that explains both the sense and the high levels of the experimentally
      observed stereoselectivity is proposed. The computations suggest that both the
      imidazolium and the carboxylic acid functionalities of histidine are viable
      hydrogen-bond donors that can stabilize the cyclic aldolization transition state.
      The stereoselectivity is proposed to arise from minimization of gauche
      interactions around the forming C-C bond.

PMID- 22458691
TI  - Authenticity of PGI "Clementine of Calabria" by multielement fingerprint.
AB  - Clementine is a citrus fruit that has found a peculiar habitat in specific areas
      of Calabria, a region located in southern Italy. Due to its peculiar
      characteristics it was recently awarded with protected geographical indications
      (PGI) from the European Union. In this work, stepwise linear discriminant
      analysis (S-LDA), soft independent modeling of class analogy (SIMCA), and partial
      least-squares discriminant analysis (PLS-DA) were used to build chemometric
      models able to protect PGI Clementine from others of different origin.
      Accordingly, the concentration of 24-26 elements was determined in peel and juice
      samples, respectively, obtained from Calabrian PGI clementine and from fruits
      cultivated in Algeria, Tunisia, and Spain. A cross-validation procedure has shown
      very satisfactory values of prediction ability for both S-LDA (96.6% for juice
      samples and 100% for peel samples) and SIMCA (100% for both peel and juice
      samples). PLS-DA models also yielded satisfactory results.

PMID- 22458690
TI  - Sequential proteolytic processing of an interferon-alpha receptor subunit by TNF
      alpha converting enzyme and presenilins.
AB  - It is well established that interferons trigger tyrosine-kinase-dependent
      signaling via JAK kinases and STAT transcription factors. However, we have
      observed both IFNaR2 receptor cleavage and functional activity of the liberated
      intracellular domain (ICD), suggesting that interferon-alpha (IFN-alpha) can also
      signal via regulated intramembrane proteolysis (RIP), an evolutionarily conserved
      mechanism of receptor-mediated signaling. Sequential cleavage of the receptor
      ectodomain and transmembrane domain is a hallmark of the most common class of
      RIP. To investigate the mechanisms of IFNaR2 RIP signaling, we examined IFNaR2
      cleavage by TNF-alpha converting enzyme (TACE) and presenilin proteases. We
      tracked the fate of epitope-tagged and fusion variants of IFNaR2 in cells
      expressing wild-type, mutant, or null versions of TACE and presenilins 1 and 2.
      Cleavage and subcellular location were determined by immunoblot, fluoresence
      microscopy, and reporter assays. We found that both TACE and presenilin 1/2
      cleave IFNaR2, in a sequential manner that allows the ICD to move to the nucleus.
      TACE cleavage was induced by IFN-alpha but was not consistently required for the
      anti-proliferative effects of IFN-alpha. In conclusion, IFNaR2 is cleaved by TACE
      and Presenilin 1/2, suggesting that interferons signal by both kinase and RIP
      mediated pathways.

PMID- 22458693
TI  - Vitamin D requirements of children: "all my life's a circle".
AB  - The importance of vitamin D for ensuring the health of children has long been
      understood. Over time, however, dietary recommendations for vitamin D intake have
      varied, with some eras seeing higher levels recommended and some lower.
      Remarkably, the current recommendations from the Institute of Medicine are not
      much different from those released with the first edition of the recommended
      dietary allowances in 1941. The present review examines the evolution of vitamin
      D recommendations over time and considers the differences and potential
      consequences related to the various recommendations in effect today. In
      considering strategies to evaluate the vitamin D status of children and efforts
      to assure its adequacy, individual caregivers and policy makers need to consider
      carefully the costs and potential risks of different screening strategies
      involving blood testing in children and of supplementation. More data on the long
      term risks and benefits are needed before widespread screening or supplementation
      can be advocated.

PMID- 22458692
TI  - Nitric oxide induces cell death in canine cruciate ligament cells by activation
      of tyrosine kinase and reactive oxygen species.
AB  - BACKGROUND: There is increasing evidence suggesting that development of
      progressive canine cranial cruciate ligament (CCL) rupture involves a gradual
      degeneration of the CCL itself, initiated by a combination of factors, ranging
      from mechanical to biochemical. To date, knowledge is lacking to what extent
      cruciate disease results from abnormal biomechanics on a normal ligament or
      contrary how far preliminary alterations of the ligament due to biochemical
      factors provoke abnormal biomechanics. This study is focused on nitric oxide
      (NO), one of the potential biochemical factors. The NO-donor sodium nitroprusside
      (SNP) has been used to study NO-dependent cell death in canine cranial and caudal
      cruciate ligament cells and to characterize signaling mechanisms during NO
      stimulation. RESULTS: Sodium nitroprusside increased apoptotic cell death dose-
      and time-dependently in cruciate ligamentocytes. Cells from the CCL were more
      susceptible to apoptosis than CaCL cells. Caspase-3 processing in response to SNP
      was not detected. Testing major upstream and signal transducing pathways, NO
      induced cruciate ligament cell death seemed to be mediated on different levels.
      Specific inhibition of tyrosine kinase significantly decreased SNP-induced cell
      death. Mitogen activated protein kinase ERK1 and 2 are activated upon NO and
      provide anti-apoptotic signals whereas p38 kinase and protein kinase C are not
      involved. Moreover, data showed that the inhibition reactive oxygen species (ROS)
      significantly reduced the level of cruciate ligament cell death. CONCLUSIONS: Our
      data support the hypothesis that canine cruciate ligamentocytes, independently
      from their origin (CCL or CaCL) follow crucial signaling pathways involved in NO
      induced cell death. However, the difference on susceptibility upon NO-mediated
      apoptosis seems to be dependent on other pathways than on these tested in the
      present study. In both, CCL and CaCL, the activation of the tyrosine kinase and
      the generation of ROS reveal important signaling pathways. In perspective, new
      efforts to prevent the development and progression of cruciate disease may
      include strategies aimed at reducing ROS.

PMID- 22458694
TI  - Role of coffee in modulation of diabetes risk.
AB  - Coffee consumption has been associated with a lower risk of type 2 diabetes. This
      association does not depend on race, gender, geographic distribution of the study
      populations, or the type of coffee consumed (i.e., caffeinated or decaffeinated).
      This review discusses the strength of this relationship, examines the possibility
      that the pattern of coffee consumption could influence the association, and
      evaluates the possible relationship between coffee consumption and other risk
      factors associated with diabetes. Particular attention is paid to the
      identification, on the basis of the scientific evidence, of the possible
      mechanisms by which coffee components might affect diabetes development,
      especially in light of the paradoxical effect of caffeine on glucose metabolism.
      In addition to the role of coffee in reducing the risk of developing type 2
      diabetes, the possible role of coffee in the course of the illness is explored.
      Finally, the possibility that coffee can also affect the risk of other forms of
      diabetes (e.g., type 1 diabetes and gestational diabetes) is examined.

PMID- 22458695
TI  - Relationship between bread consumption, body weight, and abdominal fat
      distribution: evidence from epidemiological studies.
AB  - A long-standing belief held by the general public is that bread fattens. This
      encourages many people to restrict, or even eliminate, bread from their diet. The
      present review was conducted to assess whether or not eating patterns that
      include bread are associated with overall obesity or excess abdominal adiposity,
      whether in the general population or in subjects undergoing obesity management.
      The literature search included articles published over the past 30 years that
      focused on dietary patterns that included bread (refined or whole-grain) and
      their association with ponderal status and abdominal fat distribution. A total of
      38 epidemiological studies fulfilled the inclusion criteria (22 cross-sectional,
      11 prospective cohort, and five intervention). The results indicate that dietary
      patterns that include whole-grain bread do not positively influence weight gain
      and may be beneficial to ponderal status. With respect to dietary patterns that
      include refined bread, the majority of cross-sectional studies indicate
      beneficial effects, while most of the well-designed cohort studies demonstrate a
      possible relationship with excess abdominal fat. Because differences in the study
      designs make it difficult to form definitive conclusions, more studies are needed
      that focus specifically on bread consumption, within different dietary patterns,
      and its influence on ponderal status.

PMID- 22458696
TI  - Pistachio nuts: composition and potential health benefits.
AB  - The pistachio is a nutrient-dense nut with a heart-healthy fatty-acid profile as
      well as protein, dietary fiber, potassium, magnesium, vitamin K, gamma
      tocopherol, and a number of phytochemicals. The pistachio's unique green and
      purple kernel color is a result of its lutein and anthocyanin content. Among
      nuts, pistachios contain the highest levels of potassium, gamma-tocopherol,
      vitamin K, phytosterols, and xanthophyll carotenoids. Five published randomized
      cardiovascular trials have shown that pistachios promote heart-healthy blood
      lipid profiles. Exploratory clinical studies suggest that pistachios help
      maintain healthy antioxidant and anti-inflammatory activity, glycemic control,
      and endothelial function. When consumed in moderation, pistachios may help
      control body weight because of their satiety and satiation effects and their
      reduced net metabolizable energy content. One study with subjects in a weight
      loss program demonstrated lower body mass index and triglyceride levels in
      individuals who consumed pistachios compared with those who consumed an
      isocaloric pretzel snack. Emerging research suggests that the addition of
      pistachios to high-glycemic meals may lower the overall postprandial glycemic
      response. This review examines the nutrients and phytochemicals in pistachios as
      well as the potential health effects of these nuts.

PMID- 22458697
TI  - Possible role of milk-derived bioactive peptides in the treatment and prevention
      of metabolic syndrome.
AB  - The growing prevalence of metabolic syndrome as well as its impact on public
      health has garnered increased attention in recent years. As a result, metabolic
      syndrome is now considered one of the world's leading public health problems.
      Bioactive peptides deriving from milk proteins may play an important role in the
      prevention and treatment of metabolic syndrome and its complications via several
      mechanisms, such as the satiety response, the regulation of insulinemia levels
      and blood pressure, the uptake of free radicals, and alteration of the lipid
      profile. These peptides can be incorporated into functional foods or administered
      via nutraceuticals to decrease the risk of obesity, atherogenesis, arterial
      hypertension, and type 2 diabetes. Recent findings have generated considerable
      scientific and commercial interest in milk-derived bioactive peptides, leading to
      numerous publications on the effectiveness of these substances. This review
      summarizes the current knowledge on bioactive peptides derived from milk proteins
      and examines the potential value of these peptides in the treatment and
      prevention of metabolic syndrome and its complications.

PMID- 22458699
TI  - The effect of warm up on single and intermittent-sprint performance.
AB  - Lack of benefit of warm up on prolonged intermittent-sprint performance has been
      proposed to be due to use of a pacing strategy by participants. To investigate
      this, twelve participants performed four cycle trials that consisted of either
      prolonged intermittent-sprint performance (80 min) or single-sprint performance
      (4 s), with or without a warm up. The first-sprint of intermittent-sprint
      performance was also assessed. No interaction effects (P > 0.05) were found
      between trials for intermittent-sprint performance for total work (J . kg(-1)),
      or percentage work and power decrement. Work done during the first-sprint of
      intermittent-sprint performance (no warm up) was less (P < 0.001) than the first
      sprint of intermittent-sprint performance (warm up; effect size (ES) = 0.59) and
      both single-sprint trials (warm up and no warm up; ES = 0.91, 0.75,
      respectively). Peak power (W . kg(-1)) for single-sprint (warm up) was greater (P
      < 0.05) than single-sprint (no warm up), and the first-sprint of intermittent
      sprint performance (warm up and no warm up). Warm up improved single-sprint
      performance and the first sprint of intermittent-sprint performance. Use of a
      pacing strategy probably resulted in similar intermittent-sprint performance
      between trials. These results suggest that team-sport players should perform a
      warm up at the start of a game or before substitution during a game.

PMID- 22458700
TI  - Expression of O6-methylguanine DNA methyltransferase (MGMT) and
      immunohistochemical analysis of 12 pineal parenchymal tumors.
AB  - Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of
      primary CNS tumors. Because of their rare incidence, previous reports on PPTs are
      limited in number and the useful molecular markers for deciding histological
      grading and even selecting chemotherapy are undetermined. In this study, we
      conducted immunohistochemical analysis of 12 PPT specimens, especially for
      expression of O6-methylguanine DNA methyltransferase (MGMT) to assess whether
      temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We
      analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate
      differentiation (PPTIDs), and three pineoblastomas. Immunohistochemical analysis
      was performed using antibodies against MGMT, synaptophysin, neurofilament protein
      (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of
      12 cases were positive for MGMT. The mean MIB-1 labeling index was less than 1%
      in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were
      positive for synaptophysin and 11 cases, except one PPTID case, showed positive
      for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic
      staining of NeuN was observed in five cases. No case was positive for p53. Eleven
      out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy
      to TMZ treatment. This is the first report showing MGMT expression in PPTs. In
      addition, MIB-1 labeling index correlated with WHO grade, although the
      immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the
      histological grade.

PMID- 22458701
TI  - Performance evaluation of automated fingerprint identification systems for
      specific conditions observed in casework using simulated fingermarks.
AB  - Few studies have been reported on the performance evaluation of automated
      fingerprint identification systems (AFIS) for fingermark-to-fingerprint
      comparisons. This paper aims to illustrate to fingerprint examiners the relevance
      of evaluating the AFIS performance under specific conditions by carrying out five
      types of performance tests. The conditions addressed are the number of minutiae
      assigned to a fingermark, manual and automatic assignment of the minutiae, the
      finger region from which the fingermark originates, the degree of distortion in
      the fingermark, and the difference in orientation between fingermarks and
      fingerprints. In these tests, the magnitude of the influence for each condition
      was quantified. The comparisons were performed using a research AFIS technology
      with simulated fingermarks. Simulated fingermarks provide a practical way to
      create fingermarks for specific conditions in large quantities. The results
      showed that each condition influences the performance significantly, emphasizing
      the relevance of developing, and applying performance tests for specific
      conditions.

PMID- 22458702
TI  - Submucosal glands in the columnar-lined oesophagus: evidence of an association
      with metaplasia and neosquamous epithelium.
AB  - AIM: A multipotential stem cell, possibly located in the submucosal gland ducts,
      has been suggested as the origin of metaplastic mucosa in the oesophagus. The
      topographic distribution of these glands and their excretory ducts (SMG) within
      the columnar lined oesophagus (CLO) is largely unknown. The aim of this study was
      to examine the distribution of SMG in relation to the type of overlying
      epithelium in patients with CLO. METHODS AND RESULTS: Seven oesophageal resection
      specimens were examined histologically in toto. The median frequency of SMG was
      similar in the metaplastic segments (0.12 SMG/mm) and the normal squamous
      segments (0.10 SMG/mm). Within the metaplastic segments, the median frequency of
      SMG beneath the squamous islands was significantly higher than that observed
      under the columnar lined parts (0.22 versus 0.08 SMG/mm, P = 0.046), There was a
      strong accumulation of SMG at the squamo-columnar transition zones (0.53 SMG/mm),
      which was significantly greater than that found in the columnar and squamous
      parts (P = 0.001 and 0.002, respectively). CONCLUSIONS: The relative accumulation
      of SMG beneath squamous islands and the squamo-columnar junctions within the
      metaplastic segment supports the hypothesis that both metaplastic columnar mucosa
      and neosquamous epithelium originate from a progenitor in the SMG.

PMID- 22458703
TI  - Job conditions, job satisfaction, somatic complaints and burnout among East
      African nurses.
AB  - AIMS: To describe job conditions, job satisfaction, somatic complaints and
      burnout of female East African nurses working in public and private hospitals and
      to determine how these well-being outcomes are associated with job conditions.
      BACKGROUND: Insight into job conditions, health and well-being status and their
      interrelation is virtually lacking for East African nurses. DESIGN: Cross
      sectional survey of 309 female nurses in private and public hospitals in Kenya,
      Tanzania and Uganda. METHODS: Nurses completed a survey assessing job conditions
      and job satisfaction (the Leiden Quality of Work Life Questionnaire-nurses
      version), somatic complaints (subscale of the Symptom CheckList) and burnout
      (Maslach Burnout Inventory). RESULTS: The East African nurses show high levels of
      somatic complaints, and nearly one-third of the sample would be labelled as
      burned out. In comparison with a Western European nurses reference group, the
      nurses score unfavourably on job conditions that require financial investment
      (e.g. workload, staffing, equipment and materials). On aspects related to the
      social climate (e.g. decision latitude, cooperation), however, they score more
      favourably. In comparison with private hospital nurses, public hospital nurses
      score similarly on aspects related to the social climate, but worse on the other
      job conditions. Public hospital nurses have a lower job satisfaction than private
      hospital nurses, but show comparable levels of somatic complaints and burnout.
      Strongest correlates of low job satisfaction are low supervisor support and low
      financial reward. Burnout is mainly associated with high workload and inadequate
      information provision, whereas somatic complaints are associated with demanding
      physical working conditions. CONCLUSIONS: Improvement in job conditions may
      reduce the high levels of burnout and somatic complaints and enhance job
      satisfaction in East African nurses. RELEVANCE TO CLINICAL PRACTICE: Efforts and
      investments should be made to improve the job conditions in East African nurses
      as they are key persons in the delivery of health care.

PMID- 22458704
TI  - Unilateral cutaneous mycotic septic vasculitis in a patient with Aspergillus
      vegetation in the ascending aorta.

PMID- 22458705
TI  - Solution structure of the natively assembled yeast ribosomal stalk determined by
      small-angle X-ray scattering.
AB  - The ribosomal stalk of the 60S subunit has been shown to play a crucial role in
      all steps of protein synthesis, but its structure and exact molecular function
      remain an unanswered question. In the present study, we show the low-resolution
      models of the solution structure of the yeast ribosomal stalk, composed of five
      proteins, P0-(P1-P2)(2). The model of the pentameric stalk complex determined by
      small-angle X-ray scattering reveals an elongated shape with a maximum length of
      13 nm. The model displays three distinct lobes, which may correspond to the
      individual P1-P2 heterodimers anchored to the C-terminal domain of the P0
      protein.

PMID- 22458706
TI  - Costs and difficulties of recruiting patients to provide e-health support: pilot
      study in one primary care trust.
AB  - BACKGROUND: Better use of e-health services by patients could improve outcomes
      and reduce costs but there are concerns about inequalities of access. Previous
      research in outpatients suggested that anonymous personal email support may help
      patients with long term conditions to use e-health, but recruiting earlier in
      their 'journey' may benefit patients more. This pilot study explored the
      feasibility and cost of recruiting patients for an e-health intervention in one
      primary care trust. METHODS: The sample comprised 46 practices with total patient
      population of 250,000. We approached all practices using various methods, seeking
      collaboration to recruit patients via methods agreed with each practice. A
      detailed research diary was kept of time spent recruiting practices and patients.
      Researcher time was used to estimate costs. Patients who consented to participate
      were offered email support for their use of the Internet for health. RESULTS:
      Eighteen practices agreed to take part; we recruited 27 patients, most (23/27)
      from five practices. Practices agreed to recruit patients for an e-health
      intervention via waiting room leaflets (16), posters (16), practice nurses (15),
      doctors giving patients leaflets (5), a study website link (7), inclusion in
      planned mailshots (2), and a special mailshot to patients selected from practice
      computers (1). After low recruitment response we also recruited directly in five
      practices through research assistants giving leaflets to patients in waiting
      rooms. Ten practices recruited no patients. Those practices that were more
      difficult to recruit were less likely to recruit patients. Leaving leaflets for
      practice staff to distribute and placing posters in the practice were not
      effective in recruiting patients. Leaflets handed out by practice nurses and
      website links were more successful. The practice with lowest costs per patient
      recruited (L70) used a special mailshot to selected patients. CONCLUSION:
      Recruitment via general practice was not successful and was therefore expensive.
      Direct to consumer methods and recruitment of patients in outpatients to offer
      email support may be more cost effective. If recruitment in general practice is
      required, contacting practices by letter and email, not following up non
      responding practices, and recruiting patients with selected conditions by special
      mailshot may be the most cost-effective approach.

PMID- 22458707
TI  - Insect bite-like reactions in a patient with B-cell chronic lymphocytic
      leukaemia: fluorescence in situ hybridization analysis revealed neoplastic B
      cells within the skin infiltrate.

PMID- 22458708
TI  - Forced into exile: the traumatising impact of rural aged care service
      inaccessibility.
AB  - INTRODUCTION: The shortage of residential aged care places is especially acute in
      rural areas and this results in many older people who live in these areas being
      forced to leave their home communities to access care in distant communities.
      This article reports on one aspect of a larger study that explored family and
      caring community members' experiences when someone they cared for needed to
      access residential aged care away from their rural communities. METHODS: This
      qualitative research project, informed by phenomenology, was conducted in rural
      communities of New South Wales (NSW), Australia. Participants were recruited from
      media coverage of the proposed research. Indepth interviews were conducted,
      audiotaped and transcribed.<strong> </strong>Thematic analysis was undertaken by
      two researchers independently analysing the themes and then cross-checking these
      to ensure their strength. RESULTS: The 21 interviews conducted revealed that
      inaccessibility of residential aged care places caused many to experience loss,
      loneliness and a sense of social disconnectedness. The affected rural older
      person is exiled from their home community only to return to be buried. There are
      implications for the family and the rural community who are distanced by
      kilometres, transport and finances and, more significantly, by the emotional ties
      that bind families, friends and communities. CONCLUSION: The participants whose
      experiences were explored in this article described a sense of being in exile
      when residential aged care services are inaccessible in their local communities.
      The sense of exile is felt not only by the person moving away but also by their
      family, friends and neighbours. For this reason, rural residential aged care
      service delivery should be based on the identified needs of the older person and
      those who love and care for them.

PMID- 22458709
TI  - Differences in regional cerebral blood flow response to a 5HT3 antagonist in
      early- and late-onset cocaine-dependent subjects.
AB  - 5-hydroxytryptamine 3 (5HT3) receptors are important modulators of mesostriatal
      dopaminergic transmission and have been implicated in the pathophysiology of
      cocaine reward, withdrawal and self-administration. In addition, the 5HT3
      antagonist ondansetron is effective in treating early-onset, but not late-onset,
      alcohol-dependent subjects. To explore the role of 5HT3 receptor systems in
      cocaine addiction using functioning imaging, we administered ondansetron to 23
      abstinent, treatment-seeking cocaine-addicted and 22 sex-, age- and race-matched
      healthy control participants. Differences between early- (first use before 20
      years, n = 10) and late-onset (first use after 20 years, n = 10) cocaine-addicted
      subjects were also assessed. On two separate days, subjects were administered
      ondansetron (0.15 mg/kg intravenously over 15 minutes) or saline. Regional
      cerebral blood flow (rCBF) was measured following each infusion with single
      photon emission computed tomography. No significant rCBF differences between the
      cocaine-addicted and control participants were observed following ondansetron
      relative to saline. Early-onset subjects, however, showed increased (P < 0.001)
      right posterior parahippocampal rCBF following ondansetron. In contrast, late
      onset subjects showed decreased rCBF following ondansetron in an overlapping
      region of the right parahippocampal/hippocampal gyrus. Early-onset subjects also
      displayed increased rCBF in the left anterior insula and subthalamic nucleus
      following ondansetron; late-onset subjects showed decreased rCBF in the right
      anterior insula. These findings suggest that the age of drug use onset is
      associated with serotonergic biosignatures in cocaine-addicted subjects. Further
      clarification of these alterations may guide targeted treatment with serotonergic
      medications similar to those successfully used in alcohol-dependent patients. 

PMID- 22458710
TI  - Investigation of the expression and functional significance of the novel mouse
      sperm protein, a disintegrin and metalloprotease with thrombospondin type 1
      motifs number 10 (ADAMTS10).
AB  - Fertilization represents the culmination of a series of complex interactions
      between male and female gametes. Despite advances in our understanding, the
      precise molecular mechanisms underlying these fundamental interactions remain
      largely uncharacterized. There is however growing recognition that this process
      requires the concerted action of multiple sperm receptors that possess affinity
      for complementary zona pellucida ligands and those that reside on the surface of
      the oolemma. Among the candidate sperm proteins that have been implicated in
      fertilization, those belonging to the ADAM (a disintegrin and metalloprotease)
      family of proteases have received considerable attention. The focus of the
      studies described herein has been the characterization of a closely related
      member of this protease family, ADAMTS10 (a disintegrin and metalloprotease with
      thrombospondin type 1 motifs number 10). We have demonstrated that ADAMTS10 is
      expressed during the later stages of mouse spermatogenesis and incorporated into
      the acrosomal domain of developing spermatids. During sperm maturation, the
      protein appears to be processed before being expressed on the surface of the peri
      acrosomal region of the head. Our collective data suggest that, from this
      position, ADAMTS10 participates in sperm adhesion to the zona pellucida. Indeed,
      pre-incubation of capacitated spermatozoa with either galardin, a broad spectrum
      inhibitor of metalloprotease activity, or anti-ADAMTS10 antisera elicited a
      significant reduction in their ability to engage in zona adhesion. Overall, these
      studies support the notion that sperm-oocyte interactions involve considerable
      functional redundancy and identify ADAMTS10 as a novel candidate in the mediation
      of these fundamentally important events.

PMID- 22458711
TI  - Detecting disease-associated genes with confounding variable adjustment and the
      impact on genomic meta-analysis: with application to major depressive disorder.
AB  - BACKGROUND: Detecting candidate markers in transcriptomic studies often
      encounters difficulties in complex diseases, particularly when overall signals
      are weak and sample size is small. Covariates including demographic, clinical and
      technical variables are often confounded with the underlying disease effects,
      which further hampers accurate biomarker detection. Our motivating example came
      from an analysis of five microarray studies in major depressive disorder (MDD), a
      heterogeneous psychiatric illness with mostly uncharacterized genetic mechanisms.
      RESULTS: We applied a random intercept model to account for confounding variables
      and case-control paired design. A variable selection scheme was developed to
      determine the effective confounders in each gene. Meta-analysis methods were used
      to integrate information from five studies and post hoc analyses enhanced
      biological interpretations. Simulations and application results showed that the
      adjustment for confounding variables and meta-analysis improved detection of
      biomarkers and associated pathways. CONCLUSIONS: The proposed framework
      simultaneously considers correction for confounding variables, selection of
      effective confounders, random effects from paired design and integration by meta
      analysis. The approach improved disease-related biomarker and pathway detection,
      which greatly enhanced understanding of MDD neurobiology. The statistical
      framework can be applied to similar experimental design encountered in other
      complex and heterogeneous diseases.

PMID- 22458712
TI  - A health-risk appraisal model and endoscopic mass screening for esophageal cancer
      in Japanese men.
AB  - A strong association between inactive aldehyde dehydrogenase-2 (ALDH2) and risk
      of esophageal cancer has been demonstrated in East Asian drinkers. An alcohol
      flushing questionnaire asking about past and current tendency for facial flushing
      to occur after drinking a glass (~180 mL) of beer predicts the presence of
      inactive ALDH2 among Japanese aged 40 years or older with a sensitivity and
      specificity of approximately 90%. We invented a health-risk appraisal (HRA) model
      that makes it possible to identify Japanese men who are at high risk for
      esophageal cancer based on their past and current alcohol flushing tendency,
      drinking, smoking, and intake of vegetables and fruits. Between 2008 and 2009,
      2221 Japanese men aged 50 years or older filled out the HRA questionnaire before
      undergoing a screening examination by upper gastrointestinal endoscopy at five
      medical facilities. The endoscopic examination resulted in a diagnosis of
      esophageal cancer in 19 subjects, and 117 (5.27%) subjects had an HRA score >=
      11. The proportion of subjects with an HRA score >= 11 was higher in the 50-69
      age group (6.11-6.88%) than in 70-89 age group (2.84-2.86%). The esophageal
      cancer detection rate was 4.27% among the subjects with an HRA score >= 11 and
      only 0.67% among the other subjects. Based on a receiver operating characteristic
      curve analysis, when an HRA score of >= 9 was used for subjects aged 50-69 years
      and of >= 8 for those aged 70-89 years as the cutoff value to select individuals
      with a high risk for esophageal cancer, its sensitivity and false-positive rate
      was 52.6% and 15.2%, respectively, and the cancer detection rate was 2.91% in the
      high-risk group, as opposed to 0.48% in the other group. In conclusion, the high
      detection rates for esophageal cancer in the high-risk groups encouraged
      screening based on our HRA model in larger Japanese populations.

PMID- 22458713
TI  - Biosynthesis and incorporation of side-chain-truncated lignin monomers to reduce
      lignin polymerization and enhance saccharification.
AB  - Lignocellulosic biomass is utilized as a renewable feedstock in various agro
      industrial activities. Lignin is an aromatic, hydrophobic and mildly branched
      polymer integrally associated with polysaccharides within the biomass, which
      negatively affects their extraction and hydrolysis during industrial processing.
      Engineering the monomer composition of lignins offers an attractive option
      towards new lignins with reduced recalcitrance. The presented work describes a
      new strategy developed in Arabidopsis for the overproduction of rare lignin
      monomers to reduce lignin polymerization degree (DP). Biosynthesis of these 'DP
      reducers' is achieved by expressing a bacterial hydroxycinnamoyl-CoA hydratase
      lyase (HCHL) in lignifying tissues of Arabidopsis inflorescence stems. HCHL
      cleaves the propanoid side-chain of hydroxycinnamoyl-CoA lignin precursors to
      produce the corresponding hydroxybenzaldehydes so that plant stems expressing
      HCHL accumulate in their cell wall higher amounts of hydroxybenzaldehyde and
      hydroxybenzoate derivatives. Engineered plants with intermediate HCHL activity
      levels show no reduction in total lignin, sugar content or biomass yield compared
      with wild-type plants. However, cell wall characterization of extract-free stems
      by thioacidolysis and by 2D-NMR revealed an increased amount of unusual C6C1
      lignin monomers most likely linked with lignin as end-groups. Moreover the
      analysis of lignin isolated from these plants using size-exclusion chromatography
      revealed a reduced molecular weight. Furthermore, these engineered lines show
      saccharification improvement of pretreated stem cell walls. Therefore, we
      conclude that enhancing the biosynthesis and incorporation of C6C1 monomers ('DP
      reducers') into lignin polymers represents a promising strategy to reduce lignin
      DP and to decrease cell wall recalcitrance to enzymatic hydrolysis.

PMID- 22458714
TI  - Boron-capped tris(glyoximato) cobalt clathrochelate as a precursor for the
      electrodeposition of nanoparticles catalyzing H2 evolution in water.
AB  - Electrochemical investigation of a boron-capped tris(glyoximato)cobalt
      clathrochelate complex in the presence of acid reveals that the catalytic
      activity toward hydrogen evolution results from an electrodeposition of cobalt
      containing nanoparticles on the electrode surface at a modest cathodic potential.
      The deposited particles act as remarkably active catalysts for H(2) production in
      water at pH 7.

PMID- 22458715
TI  - Healthcare-related characteristics of low vs normal folate levels among women of
      child-bearing age.
AB  - OBJECTIVE: Despite the institution of mandatory folic acid fortification in the
      US, folate deficiencies still occur and are associated with an increased risk of
      several conditions. Since little is known regarding the relationship between
      folate status and other clinical, demographic, and healthcare-related
      characteristics, the objective of the study was to compare healthcare-related
      characteristics among US child-bearing age women with low vs normal red blood
      cell (RBC) folate levels. RESEARCH DESIGN AND METHODS: Data from the 2003-2006
      National Health and Nutrition Examination Survey (NHANES) were used to conduct a
      retrospective cohort study. Women (aged 18-45 when surveyed) were categorized in
      two cohorts for comparison: normal RBC folate level (>= 140 ng/ml, NFL) and low
      RBC folate level (<140 ng/ml, LFL). RESULTS: Of the 2816 subjects, 5.9% were
      assigned to the LFL cohort and were significantly younger (28 vs 30 years,
      p=0.01); a greater proportion were 18-25 years old (55.7% vs 39.9%, p<0.001) or
      African-American (55.1% vs 22.3%, p<0.01). A lower proportion of LFL women were
      insured (67.3% vs 75.5%, p=0.01) with low rates of private insurance (39.5% vs
      53.1%, p<0.01), while Medicaid/SCHIP coverage was similar (16.8% vs 15.1%,
      p=0.56). Predictors of low folate levels included aged 36-45 years (OR: 2.14 [95%
      CI: 1.04, 4.39]) and never being married (2.65 [1.34, 5.24]), while a household
      income >= $75,000 reduced the likelihood of having low folate levels (0.20 [0.06,
      0.73]). LIMITATIONS: The proportion of women with low folate levels was small,
      with the sample size limiting the ability to adjust for other factors during
      analysis. Medical histories were based on patient interviews and are subject to
      recall bias. CONCLUSION: LFL women are younger and have low rates of private
      insurance coverage compared to women with normal folate levels. Differences in
      age, marital status, and household income are associated with folate status.

PMID- 22458716
TI  - Detection of Helicobacter pylori in bovine, buffalo, camel, ovine, and caprine
      milk in Iran.
AB  - Helicobacter pylori infection in humans is one of the most common infections
      worldwide. However, the origin and transmission of this bacterium has not been
      clearly explained. One of the suggested theories is transmission via raw milk
      from animals to human beings. This study was conducted to determine the
      prevalence rate of H. pylori in bulk milk samples from dairy bovine, buffalo,
      camel, ovine, and caprine herds in Iran. In the present study, 447 bulk milk
      samples from 230 dairy bovine, buffalo, camel, ovine, and caprine herds were
      collected in four provinces and tested for H. pylori by cultural method and
      polymerase chain reaction (PCR) for the detection of the ureC (glmM) gene. The
      animals whose milk samples collected for this study were clinically healthy.
      Using the cultural method, three of 447 milk samples (0.67%), including two sheep
      (2.2%) and one buffalo (1.6%) milk samples, were found to be contaminated with H.
      pylori. H. pylori ureC gene was detected in 56 (12.5%) of milk samples, including
      19 cow (14.1%), 11 sheep (12.2%), nine goat (8.7%), two camel (3.6%), and 15
      buffalo (23.4%) milk samples. Using PCR method, there were significant
      differences (p<0.05) in the level of contamination with H. pylori between milk
      samples collected from different species. The present study is the first report
      of the isolation of H. pylori from raw sheep and buffalo milk in Iran and the
      first demonstration of H. pylori DNA in camel and buffalo milk.

PMID- 22458717
TI  - Human enteric pathogen internalization by root uptake into food crops.
AB  - With an increasing number of outbreaks and illnesses associated with produce
      contaminated before harvest, understanding the potential and mechanisms of
      produce contamination by enteric pathogens can aid in the development of
      preventative and post-harvest processing measures to reduce microbial
      populations. Enteric pathogens localized at subsurface sites on leafy green plant
      tissue prevent their removal during washing and inactivation by sanitizers. Root
      uptake of enteric pathogens and subsequent internalization has been a large area
      of research with results varying due to differences in experimental design,
      systems tested, and pathogens and crops used. The potential for uptake of
      foodborne pathogen, both bacterial and viral, through roots into food crops is
      reviewed. Various factors shown to affect the ability of human pathogens to
      internalize include growth substrate (soil vs. hydroponic solution), plant
      developmental stage, pathogen genus and/or strain, inoculum level, and plant
      species and cultivar. Several mechanisms of internalization ("active" vs.
      "passive") of bacteria to plant roots have also been hypothesized.

PMID- 22458719
TI  - More emphasis on nurse education.

PMID- 22458718
TI  - Creating continuity out of the disruption of a diagnosis of HIV during pregnancy.
AB  - AIM: To understand the uniqueness of the experience of testing HIV positive from
      the perspective of pregnant women. BACKGROUND: As more people learn of their HIV
      diagnosis through routine screening processes, it is timely to reflect on the
      impact of receiving an unexpected positive result. DESIGN: A prospective
      qualitative study. METHODS: This paper draws on the case studies of four women
      who were participating in a larger prospective qualitative study of reproductive
      decision-making, pregnancy and childbirth following HIV diagnosis. Multiple
      interviews were conducted following diagnosis during pregnancy, and, after the
      birth of their babies. Thematic data analysis was undertaken. RESULTS: Drawing on
      Becker's theory of disruption, we document the 'sudden disjuncture' of their
      antenatal diagnosis and the embodied emotional struggle the women engaged in to
      create continuity in their lives. A diagnosis of HIV disrupted the women's
      biographies in terms of their health, relationships and social identity. As
      pregnant women, the threat of HIV was experienced most significantly in relation
      to their unborn child. However, their narratives also revealed how a diagnosis of
      HIV in the context of pregnancy, whilst traumatic, provided a focus for regaining
      continuity in their lives, as the baby became a metaphor for hope and orientation
      toward the future. CONCLUSIONS: As HIV testing becomes more 'routine', the
      findings of this study serve to remind health professionals that a positive
      diagnosis continues to constitute a major trauma to individuals and families.
      RELEVANCE TO CLINICAL PRACTICE: We propose that appropriately educated nursing
      and midwifery staff could facilitate the 'meaning making' process that is
      required for newly diagnosed HIV positive persons to find a subjective sense of
      well-being in their lives.

PMID- 22458720
TI  - Biological perspectives: remember the thyroid.

PMID- 22458721
TI  - Biological perspectives: detecting malingering of post-traumatic stress disorder
      (PTSD) in adults.

PMID- 22458722
TI  - Meet me at the crossroads: clinical research engages practitioners, educators,
      students, and patients.
AB  - PURPOSE: Many nurse researchers struggle to communicate the relevance of their
      work to colleagues in education and clinical practice, while making research
      "come alive" for graduate and undergraduate students. Last and most important,
      clinical research must be understandable and meaningful to the participants.
      DESIGN AND METHODS: Randomized trial. FINDINGS: In this article, nurses in each
      of these roles review the same research project through their unique lens,
      discussing their unique project roles, highlighting multiple meanings and
      exploring implications. PRACTICE IMPLICATIONS: We call for nurses in multiple
      roles to consider the meanings of research from multiple perspectives and to
      communicate research findings in a manner understandable to all stakeholders.

PMID- 22458723
TI  - Physical restraints in an Italian psychiatric ward: clinical reasons and staff
      organization problems.
AB  - PURPOSE: To analyze physical restraint use in an Italian acute psychiatric ward,
      where mechanical restraint by belt is highly discouraged but allowed. DESIGN AND
      METHODS: Data were retrospectively collected from medical and nursing charts,
      from January 1, 2005, to December 31, 2008. Physical restraint rate and
      relationships between restraints and selected variables were statistically
      analyzed. FINDINGS: Restraints were statistically significantly more frequent in
      compulsory or voluntary admissions of patients with an altered state of
      consciousness, at night, to control aggressive behavior, and in patients with
      "Schizophrenia and other Psychotic Disorders" during the first 72 hr of
      hospitalization. PRACTICAL IMPLICATIONS: Analysis of clinical and organizational
      factors conditioning restraints may limit its use.

PMID- 22458724
TI  - Complex contribution of combat-related post-traumatic stress disorder to veteran
      suicide: facing an increasing challenge.
AB  - PURPOSE: The purpose of this case study is to present the complex contribution of
      combat-related post-traumatic stress disorder (PTSD) to suicide and international
      standards of treatment among veterans deployed to the Middle East. CONCLUSIONS:
      PTSD carries increased physical and psychological health risk in combat soldiers.
      Internationally, guidelines for PTSD promote cognitive behavior therapies,
      specifically exposure therapy, as first line treatment; however, implementation
      varies among countries. PRACTICE IMPLICATIONS: Evidence supports the benefit of
      exposure-based psychotherapy for combat-related PTSD. Commonly prescribed
      antidepressants and other psychotherapy treatments may not be as beneficial.

PMID- 22458725
TI  - Embodying identity in chemotherapy-induced alopecia.
AB  - PURPOSE: To report concept analyses of Embodying Identity in chemotherapy-induced
      alopecia. DESIGN AND METHODS: A case study approach was used to explore
      experiences of alopecia. A transcribed interview was analyzed using
      phenomenological methods. FINDINGS AND PRACTICE IMPLICATIONS: Embodying Identity
      was supported by themes from the interview and defined as the way in which
      persons change how they view self (mind, body, spirit) in an effort to reconcile
      physical or body alterations. Individuals pass through this process experiencing
      feelings of "it's not me" to recognition of self with changes ("but, it's me")
      and finally, acceptance and incorporation into self ("it's me").

PMID- 22458726
TI  - Suppression of bladder overactivity and oxidative stress by the phytotherapeutic
      agent, Eviprostat, in a rat model of atherosclerosis-induced chronic bladder
      ischemia.
AB  - OBJECTIVES: To clarify the mechanism by which chronic bladder ischemia causes
      bladder functional changes, and to investigate the involvement of oxidative
      stress and pro-inflammatory cytokines, and the effects of the phytotherapeutic
      drug, Eviprostat, on these biochemical marker levels and bladder function.
      METHODS: Male Sprague-Dawley rats aged 15 weeks were divided into three groups.
      Arterial injury was experimentally induced by balloon endothelial injury of the
      iliac arteries, and a 2% cholesterol diet was given for 8 weeks. Rats in the
      arterial-injury group were given daily oral vehicle or Eviprostat, whereas sham
      operated animals on a regular diet (0.09% cholesterol) were given vehicle for the
      last 2 weeks. Eight weeks after surgery, the levels of bladder pro-inflammatory
      cytokines, as well as bladder and urinary oxidative-stress markers, were
      determined. Cystometrograms were carried out without anesthesia or restraint.
      RESULTS: Bladder and urinary oxidative-stress markers, and bladder pro
      inflammatory cytokine levels were significantly increased in the arterial-injury
      group, and Eviprostat markedly suppressed these increase. The cystometrograms
      showed that arterial injury decreased the intermicturition interval without
      affecting the micturition pressure. This decrease was reversed by Eviprostat
      treatment. CONCLUSIONS: Oxidative stress and pro-inflammatory cytokines might be
      involved in the development of overactive bladder by atherosclerosis-induced
      chronic bladder ischemia. Eviprostat might provide an attractive treatment option
      for individuals with bladder dysfunction due to chronic bladder ischemia because
      of its anti-oxidant and anti-inflammatory properties.

PMID- 22458727
TI  - New York State's landmark policies on oversight and compensation for egg donation
      to stem cell research.
AB  - In 2009, New York became the first US state to implement a policy permitting
      researchers to use public funds to reimburse women who donate oocytes directly
      and solely to stem cell research, not only for the woman's out-of-pocket
      expenses, but also for the time, burden and discomfort associated with the
      donation process. The debate about the propriety of such compensation was
      recently renewed with the publication of a stem cell study in which women were
      provided with compensation for donating their eggs. This article explores the
      scientific and ethical rationales that led to New York's decision to allow donor
      compensation. The multifaceted deliberation process and comprehensive policies
      may serve as a model for other states and countries considering the issue of
      oocyte donor compensation.

PMID- 22458729
TI  - A functional description of CymA, an electron-transfer hub supporting anaerobic
      respiratory flexibility in Shewanella.
AB  - CymA (tetrahaem cytochrome c) is a member of the NapC/NirT family of quinol
      dehydrogenases. Essential for the anaerobic respiratory flexibility of
      shewanellae, CymA transfers electrons from menaquinol to various dedicated
      systems for the reduction of terminal electron acceptors including fumarate and
      insoluble minerals of Fe(III). Spectroscopic characterization of CymA from
      Shewanella oneidensis strain MR-1 identifies three low-spin His/His co-ordinated
      c-haems and a single high-spin c-haem with His/H(2)O co-ordination lying adjacent
      to the quinol-binding site. At pH 7, binding of the menaquinol analogue, 2-heptyl
      4-hydroxyquinoline-N-oxide, does not alter the mid-point potentials of the high
      spin (approximately -240 mV) and low-spin (approximately -110, -190 and -265 mV)
      haems that appear biased to transfer electrons from the high- to low-spin centres
      following quinol oxidation. CymA is reduced with menadiol (E(m) = -80 mV) in the
      presence of NADH (E(m) = -320 mV) and an NADH-menadione (2-methyl-1,4
      naphthoquinone) oxidoreductase, but not by menadiol alone. In cytoplasmic
      membranes reduction of CymA may then require the thermodynamic driving force from
      NADH, formate or H2 oxidation as the redox poise of the menaquinol pool in
      isolation is insufficient. Spectroscopic studies suggest that CymA requires a non
      haem co-factor for quinol oxidation and that the reduced enzyme forms a 1:1
      complex with its redox partner Fcc3 (flavocytochrome c3 fumarate reductase). The
      implications for CymA supporting the respiratory flexibility of shewanellae are
      discussed.

PMID- 22458730
TI  - Professor James M. Tanner and the sport sciences.
AB  - BACKGROUND: Although Tanner was not directly involved in physical education or
      the sport sciences, several of his papers addressed issues related to research in
      the area. AIM: To consider the implications of selected papers and research
      projects for the sport sciences. PAPERS AND IMPLICATIONS: Several early papers
      addressed ratio standards, somatotype and total cholesterol, and anthropometric
      and somatotype changes associated weight training and cessation of training in
      young adult men. The papers have, respectively, implications for current studies
      of allometric scaling, physique and risk factors for cardiovascular and metabolic
      complications, and responses to training. The survey of athletes at the 1960 Rome
      Olympic Games not only added to the literature but to some extent also set the
      stage for subsequent surveys of Olympic athletes in 1968, 1972 and 1976. Although
      not directly involved in the mixed-longitudinal study of Training of Youth
      Athletes (TOYA) in several sports, it was conducted in his department. Results
      from TOYA indicated no influence of systematic training for sport on growth in
      height, young adult height and sexual maturation. Growth at Adolescence was also
      a fixture in many graduate programs. CONCLUSION: Though not a sport scientist,
      Tanner contributed directly and indirectly to the field.

PMID- 22458728
TI  - Medications development to treat alcohol dependence: a vision for the next
      decade.
AB  - More than 76 million people world-wide are estimated to have diagnosable alcohol
      use disorders (AUDs) (alcohol abuse or dependence), making these disorders a
      major global health problem. Pharmacotherapy offers promising means for treating
      AUDs, and significant progress has been made in the past 20 years. The US Food
      and Drug Administration approved three of the four medications for alcoholism in
      the last two decades. Unfortunately, these medications do not work for everyone,
      prompting the need for a personalized approach to optimize clinical benefit or
      more efficacious medications that can treat a wider range of patients, or both.
      To promote global health, the potential reorganization of the National Institutes
      of Health (NIH) must continue to support the National Institute on Alcohol Abuse
      and Alcoholism's (NIAAA's) vision of ensuring the development and delivery of new
      and more efficacious medications to treat AUDs in the coming decade. To achieve
      this objective, the NIAAA Medications Development Team has identified three
      fundamental long-range goals: (1) to make the drug development process more
      efficient; (2) to identify more efficacious medications, personalize treatment
      approaches, or both; and (3) to facilitate the implementation and adaptation of
      medications in real-world treatment settings. These goals will be carried out
      through seven key objectives. This paper describes those objectives in terms of
      rationale and strategy. Successful implementation of these objectives will result
      in the development of more efficacious and safe medications, provide a greater
      selection of therapy options and ultimately lessen the impact of this devastating
      disorder.

PMID- 22458731
TI  - A fast and efficient polymerase chain reaction-based method for the preparation
      of in situ hybridization probes.
AB  - AIMS: In situ hybridization (ISH) is the method of choice for analysis of the
      local distribution of gene expression in tissue samples at the cellular level. In
      this study we present a rapid and efficient protocol for the generation of
      labelled cRNA probes. METHODS AND RESULTS: The protocol is based on the
      preparation of DNA in vitro transcription templates using polymerase chain
      reaction (PCR), using primers that include RNA polymerase promoter sequences and
      size-based purification of PCR fragments containing the target gene-specific cDNA
      and promoter elements for T7 and SP6 RNA polymerase. The optimized purification
      protocols ensure high transcription efficiency and target specificity of the
      labelled cRNA. The cRNA hybridization probes obtained are compatible with
      established in situ hybridization protocols. CONCLUSIONS: Purified PCR fragment
      based in vitro transcription enables preparation of in situ hybridization probes
      which allow the rapid detection of gene expression distribution in tissue slices
      from any gene of interest.

PMID- 22458732
TI  - Cutaneous involvement in multiple myeloma: report of two cases.

PMID- 22458733
TI  - Inflammatory responses to induced infectious endometritis in mares resistant or
      susceptible to persistent endometritis.
AB  - BACKGROUND: The objective of the study was to evaluate the gene expression of
      inflammatory cytokines (interleukin [IL]-1beta, IL-6, IL-8, IL-10, tumor necrosis
      factor [TNF]-alpha, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in
      endometrial tissue and circulating leukocytes in response to uterine inoculation
      of 105 colony forming units (CFU) Escherichia coli in mares. Before inoculation,
      mares were classified as resistant or susceptible to persistent endometritis
      based on their uterine inflammatory response to infusion of 109 killed
      spermatozoa and histological assessment of the endometrial quality. Endometrial
      biopsies were obtained 3, 12, 24 and 72 hours (h) after bacterial inoculation and
      blood samples were obtained during the 7 day period post bacterial inoculation.
      Expression levels of cytokines and SAA were determined by quantitative real-time
      reverse transcriptase PCR (qRT-PCR). RESULTS: Compared to levels in a control
      biopsy (obtained in the subsequent estrous), resistant mares showed an up
      regulation of IL-1beta, IL-6, IL-8 and TNF-alpha at 3 h after E. coli
      inoculation, while susceptible mares showed increased gene expression of IL-6 and
      IL-1ra. Susceptible mares had a significant lower gene expression of TNF-alpha,IL
      6 and increased expression of IL-1ra 3 h after E. coli inoculation compared to
      resistant mares. Susceptible mares showed a sustained and prolonged inflammatory
      response with increased gene expression levels of IL-1beta, IL-8, IL-1ra and IL
      1beta:IL-1ra ratio throughout the entire study period (72 h), whereas levels in
      resistant mares returned to estrous control levels by 12 hours. Endometrial mRNA
      transcripts of IL-1beta and IL-1ra were significantly higher in mares with heavy
      uterine bacterial growth compared to mares with no/mild growth.All blood
      parameters were unaffected by intrauterine E. coli infusion, except for a lower
      gene expression of IL-10 at 168 h and an increased expression of IL-1ra at 48 h
      observed in susceptible mares compared to resistant mares. CONCLUSIONS: The
      current investigation suggests that endometrial mRNA transcripts of pro
      inflammatory cytokines in response to endometritis are finely regulated in
      resistant mares, with initial high expression levels followed by normalization
      within a short period of time. Susceptible mares had a prolonged expression of
      pro-inflammatory cytokines, supporting the hypothesis that an unbalanced
      endometrial gene expression of inflammatory cytokines might play an important
      role in the pathogenesis of persistent endometritis.

PMID- 22458734
TI  - A qualitative study of professional and client perspectives on information flows
      and decision aid use.
AB  - BACKGROUND: This paper explores the meanings given by a diverse range of
      stakeholders to a decision aid aimed at helping carers of people in early to
      moderate stages of dementia (PWD) to select community based respite services.
      Decision aids aim to empower clients to share decision making with health
      professionals. However, the match between health professionals' perspectives on
      decision support needs and their clients' perspective is an important and often
      unstudied aspect of decision aid use. METHODS: A secondary analysis was
      undertaken of qualitative data collected as part of a larger study. The data
      included twelve interviews with carers of people with dementia, three interviews
      with expert advisors, and three focus groups with health professionals. A
      theoretical analysis was conducted, drawing on theories of 'positioning' and
      professional identity. RESULTS: Health professionals are seen to hold varying
      attitudes and beliefs about carers' decision support needs, and these appeared to
      be grounded in the professional identity of each group. These attitudes and
      beliefs shaped their attitudes towards decision aids, the information they
      believed should be offered to dementia carers, and the timing of its offering.
      Some groups understood carers as needing to be protected from realistic
      information and consequently saw a need to filter information to carer clients.
      CONCLUSION: Health professionals' beliefs may cause them to restrict information
      flows, which can limit carers' ability to make decisions, and limit health
      services' ability to improve partnering and shared decision making. In an era
      where information is freely available to those with the resources to access it,
      we question whether health professionals should filter information.

PMID- 22458735
TI  - Development of a new antibody for detecting natural killer enhancing factor
      (NKEF)-like protein in infected salmonids.
AB  - The main cellular responses of innate immunity are phagocytic activity and the
      respiratory burst, which produces a high amount of reactive oxygen species.
      Natural killer enhancing factor (NKEF) belongs to the peroxiredoxin family that
      has an antioxidant function and enhances cytotoxic cell activity. This molecule
      may play a key role in macrophage and cytotoxic cell communication during the
      innate immune response of fish against pathogens. In fish, the NKEF gene has been
      characterized in some species as showing an up-regulation in infected fish,
      suggesting a trigger effect upon NK-like cells. To detect and localize this
      molecule in salmonids at protein level, a monospecific polyclonal antibody was
      generated. A probable NKEF-like protein epitope region was identified and
      characterized using bioinformatic tools, and the sequence was chemically
      synthesized using Fmoc strategy, analysed by RP-HPLC and its molecular weight
      confirmed by mass spectrometry. The synthetic peptide was immunized and
      antibodies from ascitic fluid were obtained. The resulting antibody is a
      versatile tool for detecting NKEF by different immune techniques such as ELISA,
      Western blotting and immunohistochemistry. Analysis of NKEF-like protein is a
      useful method for characterizing immune properties of this molecule in fish
      during response to pathogens.

PMID- 22458736
TI  - Postmortem vitreous beta-hydroxybutyrate: interpretation in a forensic setting.
AB  - Vitreous beta-hydroxybutyrate (BHB) was retrospectively analyzed in 1795 forensic
      cases using the Pointe Scientific method. Comparison of vitreous BHB with
      vitreous glucose in 1781 of the cases showed moderately good correlation r =
      0.731. Comparison with blood alcohol levels in 1561 of the cases showed no
      correlation r = -0.053. Vitreous BHB was a marker of diabetic ketoacidosis when
      above 6.0 mM with a vitreous glucose over 200 mg/dL. It was an indicator (>50%)
      for alcoholic ketoacidosis when above 6.0 mM with a vitreous glucose below 200
      mg/dL. Recommendations for interpretation of vitreous BHB: <0.4 mM normal; 0.41
      1.2 mM slightly elevated, rarely (<1%) of concern; 1.21-2.0 mM moderately
      elevated, less rarely (2.5%) of concern; 2.01-6.0 mM significantly elevated,
      frequently of concern (12-48%); >6.0 mM usually (100% in this study) indicated
      life-threatening conditions. Vitreous BHB was helpful evaluating cases with
      ketogenic conditions, especially diabetes and alcoholism.

PMID- 22458737
TI  - Epigenetic inactivation of the E-cadherin gene in eyelid sebaceous gland
      carcinoma.
AB  - BACKGROUND: E-cadherin and beta-catenin are crucial components of the cell-cell
      adhesion complex. Their loss has often been associated with tumour metastasis and
      poor clinical outcome. Both loss of E-cadherin at the cell membrane and a
      stabilizing mutation in CTNNB1 (beta-catenin gene) have been associated with
      ovarian, colorectal, hepatocellular and nonmelanoma skin cancer, such as squamous
      and basal cell carcinomas. Absence of E-cadherin may be caused by promoter
      hypermethylation of the E-cadherin gene (CDH1). OBJECTIVES: To determine the role
      of E-cadherin promoter hypermethylation and CTNNB1 gene mutation in the
      aggressive behaviour of sebaceous gland carcinoma of the eyelid. METHODS: Thirty
      six cases of sebaceous gland carcinoma were subjected to E-cadherin methylation
      specific polymerase chain reaction and mutational analysis for the CTNNB1 gene. E
      cadherin and beta-catenin staining was evaluated by immunohistochemistry. Results
      were correlated with the clinicopathological features of sebaceous gland
      carcinoma. RESULTS: nMethylation of the E-cadherin promoter region was detected
      in 72% of eyelid sebaceous gland carcinoma cases and loss of E-cadherin
      immunostaining in 83%. E-cadherin promoter hypermethylation showed a significant
      association with the loss of membranous E-cadherin (P = 0.038) and it was of
      borderline significance with reduced disease-free survival (P = 0.05). It was
      also found to be associated with advanced age (73%), tumour size >= 2 cm (77%),
      orbital invasion (83%), lymph node metastasis (60%), tumour recurrence (60%) and
      poor histological differentiation (90%). DNA sequencing revealed no stabilizing
      beta-catenin gene mutation in sebaceous gland carcinoma. Loss of membranous beta
      catenin was observed in 61% cases, which associated significantly with both E
      cadherin promoter methylation (P = 0.0262) and loss of E-cadherin membranous
      localization (P=0.0015). CONCLUSION: Epigenetic inactivation of the E-cadherin
      gene causes loss of membrane-bound E-cadherin and could contribute to the reduced
      disease-free survival in eyelid sebaceous gland carcinoma. Mutations in the beta
      catenin gene do not seem to be involved in the pathogenesis of eyelid sebaceous
      gland carcinoma.

PMID- 22458739
TI  - A simplified mechanistic algorithm for treating resistant hypertension: efficacy
      in a retrospective study.
AB  - This retrospective study assessed the efficacy of a recently described, mechanism
      based algorithm for treating resistant hypertension. Charts of consecutive
      patients seen for resistant hypertension were reviewed. Algorithm-based
      intervention was limited to either or both of just 2 options: (1) strengthening
      of the diuretic regimen, usually with addition of spironolactone; and (2)
      treatment with the combination of an alpha- + nonmetabolized beta-blocker. Of 27
      patients, 24 (89%) achieved control, including 13 (54%) in whom the diuretic
      regimen was strengthened, 6 (25%) in whom alpha-/beta-blockade was instituted,
      and 5 (21%) who received both interventions. The most frequent medication
      adjustments were addition of a potassium-sparing diuretic in 16 (67%), doxazosin
      in 9 (37.5%), and replacing a metabolized with a nonmetabolized beta-blocker in 6
      (25%). The authors conclude that treatment based on this algorithm can both
      simplify and improve the management of resistant hypertension and merits further
      evaluation in prospective studies.

PMID- 22458738
TI  - Emergency care of esophageal foreign body impactions: timing, treatment
      modalities, and resource utilization.
AB  - Esophageal foreign body impaction (EFBI) often requires urgent evaluation and
      treatment, but characteristics of emergency department (ED) care such as timing
      of presentation and therapeutic procedures and costs of care are unknown. We
      aimed to study health-care utilization for patients with EFBI presenting to the
      ED. Cases of EFBI from 2002 to 2009 were identified by querying three different
      databases from the University of North Carolina Hospitals for all records with
      ICD-9 CM code 935.1: 'foreign body in the esophagus.' Charts were reviewed to
      confirm EFBI and extract pertinent data related to the ED visit, including time
      of presentation, length of ED stay, medications administered, type of procedure
      performed, characteristics of procedures, and time to therapeutic procedure.
      Hospital charges for EFBI encounters and consult fees were determined from the
      Physicians' Fee Reference 2010, and were compiled to estimate costs. Of the 548
      cases of EFBI identified, 351 subjects (64%) presented to the ED. A total of 118
      (34%) patients received a medication to treat EFBI, which was only effective in
      8% of those patients. Two hundred ninety (83%) subjects underwent a procedure
      including esophagogastroduodenoscopy (EGD) (n=206) or ear, nose, and throat
      surgery (ENT)-performed laryngoscopy/esophagoscopy (n=138). Admission to the
      hospital occurred in 162 (46%) of cases. There was no relationship between ED
      arrival time and time-to-procedure or total time in ED. There was also no
      significant relationship between delivery of ED medications and likelihood of
      undergoing a procedure, or between ED arrival time and delivery of medications.
      The charges associated with a typical EFBI episode ranged from $2284-$6218. In
      conclusion, the majority of patients with EFBI at our institution presented to
      the ED. Medical management was largely ineffective. A therapeutic procedure was
      required to clear the EFBI in most patients. Time of ED arrival made no
      difference in time-to-procedure, indicating that gastroenterology and ENT
      specialists recognize the urgency of treating EFBI regardless of time of day.

PMID- 22458740
TI  - Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide,
      endothelial-derived hyperpolarizing factors, and prostaglandins.
AB  - Under resting conditions the arterial vasculature exists in a vasoconstricted
      state referred to as vascular tone. Physiological dilatation in response to
      increased flow, a function of normal endothelium is necessary to maintain normal
      blood pressure. Endothelial dysfunction in vascular smooth muscle cells thus
      results in loss of normal vasorelaxant function and the inability of arteries to
      appropriately dilate in response to increased blood flow in either a systemic or
      regional vascular bed, resulting in increased blood pressure, a sequence that may
      represent a common pathway to hypertension. Normal vasorelaxation is mediated by
      a number of endothelial systems including nitric oxide (NO), prostaglandins (PGI2
      and PGE2), and a family of endothelial-derived hyperpolarizing factors (EDHF). In
      response to hemodynamic shear stress, endothelium continuously releases NO, EDHF,
      and PGI2 to provide vasodilatation. EDHF, not a single molecule but rather a
      group of molecules that includes epoxyeicosatrienoic acids, hydrogen peroxide,
      carbon monoxide, hydrogen sulfide, C-natriuretic peptide, and K+ itself, causes
      vasodilatation by activation of vascular smooth muscle cell K+ channels,
      resulting in hyperpolarization and thus vasorelaxation. The understanding and
      effective management of blood pressure requires an understanding of both
      physiologic and pathophysiologic regulation of vascular tone. This review
      describes molecular mechanisms underlying normal endothelial regulation and
      pathological states, such as increased oxidative stress, which cause loss of
      vasorelaxation. Possible pharmacological interventions to restore normal function
      are suggested.

PMID- 22458742
TI  - Page kidney: etiology, renal function outcomes and risk for future hypertension.
AB  - The initial description of Page kidney, a form of renin-mediated hypertension,
      included athletes with renal subcapsular hematoma after flank trauma.
      Subsequently, nontraumatic etiologies were identified. In this study, the authors
      compare traumatic and nontraumatic causes of Page kidney. All cases with
      hypertension attributable to renal hematoma at our institution from 1960 to 2010
      were reviewed. Twenty-six patients (9 trauma, 17 nontrauma), with a mean age of
      36.7 years, were included. Trauma patients were younger (P<.001), had lower
      systolic blood pressures (P=.011), and higher baseline estimated glomerular
      filtration rate (eGFR), (P=.027) at presentation. No differences in presenting
      features, imaging, urinalysis, or pathology are noted. Nontrauma cases required
      more antihypertensive medications (P=.001) and had higher nephrectomy rates. eGFR
      improved in all, but more in, trauma cases (P=.05). Through the analysis of 26
      cases of Page kidney, two distinct groups were identified. Trauma patients tended
      to be younger, male, have less renal impairment and lower systolic blood
      pressure. Nontrauma patients required more antihypertensive medications and had a
      higher nephrectomy rate. New-onset hypertension occurred independent of etiology,
      calling for close surveillance of blood pressures.

PMID- 22458743
TI  - Evaluation of blood pressure measurement and agreement in an academic health
      sciences center.
AB  - The authors assessed the process of blood pressure (BP) measurement and level of
      adherence to recommended procedures at representative sites throughout a large
      academic health sciences center. A casual observer assessed the setting and
      observed the process, noting the equipment, technique, and BP recorded by site
      personnel. A trained observer then repeated the patient's BP measurement
      following American Heart Association recommendations. Significant biases were
      observed between measurements by site personnel and the trained observer. Site
      personnel reported on average an increased systolic BP (SBP) of 5.66 mm Hg (95%
      confidence interval [CI], 3.09-8.23; P<.001) and a decreased diastolic BP (DBP)
      of -2.96 mm Hg (95% CI, -5.05 to -0.87; P=.005). Overall, 41% of patients had a
      >=10-mm Hg difference in SBP between measurements. Similarly, 54% had differences
      of >=5 mm Hg in DBP between measurements. Inaccurate BP measurement and poor
      technique may lead to misclassification, misdiagnosis, and inappropriate medical
      decisions. Concordance of measured SBP between our site personnel and trained
      observer was less than optimal. Several areas for improvement were identified.
      Routine calibration and use of system-wide standardized equipment, establishment
      of BP measurement protocols, and periodic technique and equipment recertification
      can be addressed in future quality initiatives.

PMID- 22458745
TI  - Agreement between community pharmacy and ambulatory and home blood pressure
      measurement methods to assess the effectiveness of antihypertensive treatment:
      the MEPAFAR study.
AB  - The usefulness of the community pharmacy blood pressure (CPBP) method in the
      diagnosis or treatment of hypertension has not been adequately addressed in
      controlled studies. The authors' aim was to assess the agreement between awake
      ambulatory blood pressure (ABP), home blood pressure (HBP), and CPBP in treated
      hypertensive patients. This was a cross-sectional study carried out in 169
      patients in which blood pressure (BP) was measured at the pharmacy (4 visits), at
      home (4 days), and by 24-hour ABP monitoring. Lin correlation-concordance
      coefficient (CCC) and Bland-Altman plots were used to evaluate quantitative
      agreement. The qualitative agreement to establish the degree of BP control was
      evaluated using kappa coefficient. The agreement was acceptable between HBP and
      CPBP (CCC=0.80 for systolic BP [SBP] and 0.80 for diastolic BP [DBP]; kappa=0.62)
      and moderate between awake ABP and CPBP (CCC=0.74/0.67, respectively;
      kappa=0.56). The Bland-Altman plots also showed lowest mean differences (0.5/0.3
      for SBP and DBP, respectively) for the comparison between CPBP and HBP. The CPBP
      has a better agreement with HBP than with awake ABP. Thus, the CPBP measurement
      method could be a good alternative to HBP monitoring, whereas it cannot be used
      as a screening test to assess the degree of BP control by awake ABP.

PMID- 22458746
TI  - Improvement of arterial stiffness by reducing oxidative stress damage in elderly
      hypertensive patients after 6 months of atorvastatin therapy.
AB  - Atorvastatin is postulated to improve arterial stiffness in patients with
      diabetes mellitus or hypercholesterolemia; however, in elderly hypertensive
      patients, its effect on arterial stiffness and the possible mechanisms are
      unknown. A total of 73 elderly hypertensive patients were enrolled to receive
      atorvastatin for 6 months. Brachial-ankle pulse wave velocity (baPWV) and
      circulating biomarkers were measured before and after the intervention. After 6
      months of treatment, the patients experienced a 19.66% reduction in low-density
      lipoprotein cholesterol (2.90+/-0.58 vs 2.33+/-0.56 mmol/L, P<.01) and a 10.63%
      reduction in baPWV (2100.89+/-513.21 vs 1877.56+/-432.06 cm/s, P=.01). In
      addition, a 21.79% reduction in circulating N-(epsilon)-carboxymethyl-lysine and
      a 20% reduction in Von Willebrand factor level were observed after treatment.
      Meanwhile, the activity of copper/zinc-containing superoxide dismutase (Cu/Zn
      SOD) was increased by 26.64% (5.04+/-1.01 vs 6.87+/-1.83 U/L, P<.001).
      Correlation analysis demonstrated that the increase of Cu/Zn SOD activity was
      related to the reductions of arterial stiffness (r=-0.340, P=.003). Taken
      together, these findings suggest that atorvastatin can improve arterial stiffness
      possibly by reducing oxidative stress levels in elderly hypertensive patients.

PMID- 22458744
TI  - Sex differences in the endothelial function of untreated hypertension.
AB  - Vascular endothelial dysfunction is associated with increased risk for adverse
      cardiovascular (CV) events. However, less is known about sex differences in the
      endothelial function of untreated hypertensive individuals. The purpose of this
      study was to assess endothelial function in women and men with untreated
      hypertension. Ninety participants (35 women, 55 men), aged 40 to 60 years (mean
      age, 46.1+/-8.2 years), with untreated stage 1 hypertension (systolic blood
      pressure 140-159 mm Hg and/or diastolic blood pressure 90-99 mm Hg) underwent
      brachial artery endothelial-dependent flow-mediated dilation and endothelial
      independent glyceryl trinitrate dilation. Women had a smaller flow-mediated
      dilation response than men (adjusted mean+/-standard error of the mean [SEM];
      1.8+/-0.6% vs 3.9+/-0.4%, P=.036), adjusting for baseline arterial diameter
      (P=.004), age (P=.596), ethnicity (P=.496), log shear stress ratio (P<.001), body
      mass index (P=.009), 24-hour diastolic blood pressure (P=.169), high-density
      lipoprotein (P=.225), log creatinine (P=.927), and log physical activity
      (P=.682). Glyceryl trinitrate dilation did not differ by sex in adjusted models.
      Women between the ages of 40 and 60 years with untreated stage 1 hypertension
      exhibited a greater impairment of endothelial function compared with their male
      counterparts. These findings raise the possibility that female sex may impart a
      greater risk of CV events in patients with untreated stage 1 hypertension
      potentially due to poorer endothelial function.

PMID- 22458741
TI  - Single-pill combination of telmisartan/amlodipine in patients with severe
      hypertension: results from the TEAMSTA severe HTN study.
AB  - This 8-week, randomized, double-blind, controlled study compared efficacy and
      tolerability of telmisartan/amlodipine (T/A) single-pill combination (SPC) vs the
      respective monotherapies in 858 patients with severe hypertension
      (systolic/diastolic blood pressure [SBP/DBP] >=180/95 mm Hg). At 8 weeks, T/A
      provided significantly greater reductions from baseline in seated trough cuff
      SBP/DBP (-47.5 mm Hg/-18.7 mm Hg) vs T (P<.0001) or A (P=.0002) monotherapy;
      superior reductions were also evident at 1, 2, 4, and 6 weeks. Blood pressure
      (BP) goal and response rates were consistently higher with T/A vs T or A. T/A was
      well tolerated, with less frequent treatment-related adverse events vs A (12.6%
      vs 16.4%) and a numerically lower incidence of peripheral edema and treatment
      discontinuation. In conclusion, treatment of patients with substantially elevated
      BP with T/A SPCs resulted in high and significantly greater BP reductions and
      higher BP goal and response rates than the respective monotherapies. T/A SPCs
      were well tolerated.

PMID- 22458747
TI  - Patient factors, but not provider and health care system factors, predict
      medication adherence in hypertensive black men.
AB  - The problem of medication adherence is pronounced in hypertensive black men.
      However, factors influencing their adherence are not well understood. This
      secondary analysis of the ongoing Counseling African Americans to Control
      Hypertension (CAATCH) randomized clinical trial investigated the patient,
      provider, and health care system factors associated with medication adherence
      among hypertensive black men. Participants (N=253) were aged 56.6+/-11.6 years,
      earned <$20,000 yearly (72.7%), and almost one half were on Medicaid (44%). Mean
      systolic blood pressure was 148.7+/-15.8 mm Hg and mean diastolic blood pressure
      was 92.7+/-9.8 mm Hg. Over one half of participants (54.9%) were nonadherent. In
      a hierarchical regression analysis, the patient factors that predicted medication
      adherence were age, self-efficacy, and depression. The final model accounted for
      32.1% of the variance (F=7.80, df 10, 165, P<.001). In conclusion, age, self
      efficacy, and depression were associated with antihypertensive medication
      adherence in black men followed in Community/Migrant Health Centers. Age is a
      characteristic that may allow clinicians to predict who may be at risk for poor
      medication adherence. Depression can be screened for and treated. Self-efficacy
      is modifiable and its implications for practice would be the development of
      interventions to increase self-efficacy in black men with hypertension.

PMID- 22458748
TI  - Misdiagnosis of aortic dissection: experience of 361 patients.
AB  - Aortic dissection (AD) is a life-threatening condition that requires immediate
      diagnosis and surgical correction. Patients with acute AD usually present
      clinically with an insignificant medical history, leading to a high probability
      of misdiagnosis. The aim of the present study was to investigate the number of
      misdiagnoses of patients with AD in order to understand this problem and to avoid
      future misdiagnosis in the emergency department. Clinical data from 361 patients
      with AD admitted between January 2003 and June 2008 were reviewed as part of a
      retrospective chart review. Diagnosis of AD was made using either chest x-ray,
      computed tomography, magnetic resonance imaging, or angiography. Fifty-one
      patients had an initial misdiagnosis (14.1%), later found to have experienced AD.
      The condition may clinically present in a varied number of manifestations,
      including syncope, chest pain, abdominal pain, back pain, acute congestive heart
      failure, or alternatively with minimal symptoms. Persons of any age can
      experience an AD, with key clinical manifestations of pain. Echocardiography can
      be used for primary examination of patients with suspected AD; however, a
      definite diagnosis is usually made using computed tomographic or magnetic
      resonance angiography. Care should be taken, particularly in the emergency
      department, to maintain a level of suspicion for AD diagnosis in order to avoid
      the potential for misdiagnosis.

PMID- 22458749
TI  - Individual risk.
AB  - Patients don't have an "individual risk" or unique probability of an outcome.
      Outside Mendelian inheritance, risks are conditional probabilities and differ as
      the risk factors included differ, at times substantially. This lack of
      reliability is an inherent limitation and is not resolved by including additional
      risk factors. Groups of like individuals need to be assembled to measure the
      probability of an outcome. Many groups, like any individual, can be identified,
      eg, groups of the same age, sex, race, or any combination of these attributes (or
      any others). That each of these groups may have different risk means there is no
      such thing as individual risk. This issue was identified by John Venn in 1866 and
      is known as the reference class problem. Models relate risk factors to outcomes
      in populations. The number calculated for an individual should not be reported as
      their individual or true risk, nor should it be used as the sole criterion for
      clinical decisions. Instead, Feinstein proposed relying on clinically important
      subgroups. An example would be utilizing an individual's blood pressure as the
      primary determinant of hypertension treatment decisions, not an unreliable
      individual risk estimate.

PMID- 22458750
TI  - The salt controversy and hypertension.

PMID- 22458751
TI  - NHANES data highlight the clinical characteristics of those with poorly
      controlled hypertension.

PMID- 22458752
TI  - Seasonal variation in hypertensive emergency hospitalization.

PMID- 22458753
TI  - Cyclophosphamide-induced hypertensive encephalopathy in a young girl with lupus.

PMID- 22458754
TI  - Spiral cleavage and early embryology of a loxosomatid entoproct and the
      usefulness of spiralian apical cross patterns for phylogenetic inferences.
AB  - BACKGROUND: Among the four major bilaterian clades, Deuterostomia, Acoelomorpha,
      Ecdysozoa, and Lophotrochozoa, the latter shows an astonishing diversity of
      bodyplans. While the largest lophotrochozoan assemblage, the Spiralia, which at
      least comprises Annelida, Mollusca, Entoprocta, Platyhelminthes, and Nemertea,
      show a spiral cleavage pattern, Ectoprocta, Brachiopoda and Phoronida (the
      Lophophorata) cleave radially. Despite a vast amount of recent molecular
      phylogenetic analyses, the interrelationships of lophotrochozoan phyla remain
      largely unresolved. Thereby, Entoprocta play a key role, because they have
      frequently been assigned to the Ectoprocta, despite their differently cleaving
      embryos. However, developmental data on entoprocts employing modern methods are
      virtually non-existent and the data available rely exclusively on sketch
      drawings, thus calling for thorough re-investigation. RESULTS: By applying
      fluorescence staining in combination with confocal microscopy and 3D-imaging
      techniques, we analyzed early embryonic development of a basal loxosomatid
      entoproct. We found that cleavage is asynchronous, equal, and spiral. An apical
      rosette, typical for most spiralian embryos, is formed. We also identified two
      cross-like cellular arrangements that bear similarities to both, a "molluscan
      like" as well as an "annelid-like" cross, respectively. CONCLUSIONS: A broad
      comparison of cleavage types and apical cross patterns across Lophotrochozoa
      shows high plasticity of these character sets and we therefore argue that these
      developmental traits should be treated and interpreted carefully when used for
      phylogenetic inferences.

PMID- 22458755
TI  - Economic burden of hepatitis C-associated diseases: Europe, Asia Pacific, and the
      Americas.
AB  - BACKGROUND: Globally, hepatitis C virus (HCV) infects ~3% of the population. The
      objective of this study was to review published work and determine the direct
      medical costs for diseases associated with HCV infection globally, with the
      exception of the US. METHODS: A systematic literature search was conducted to
      identify studies reporting the costs of hepatitis C sequelae between January 1990
      and January 2011. Over 400 references were identified, of which 45 were
      pertinent. The costs were compiled, converted to US dollars, and adjusted to 2010
      costs using the medical component of the consumer price index. RESULTS: The
      median cost of liver transplants was estimated at $139,070 ($15,430-$443,700),
      refractory ascites at $16,740 ($8990-$35,940), hepatocellular carcinoma (HCC) at
      $15,310 ($3370-$84,710), decompensated cirrhosis at $14,660 ($3810-$48,360),
      variceal hemorrhage at $12,190 ($3550-$46,120), hepatic encephalopathy at $9180
      ($5370-$50,120), diuretic sensitive ascites at $3400 ($1320-$7470), compensated
      cirrhosis at $820 ($50-$2890), and chronic hepatitis C at $280 ($90-$1860). The
      variation among studies was mainly due to the methodology used to assess cost,
      local cost and government reimbursement, and country-specific treatment
      protocols. LIMITATIONS: All costs were adjusted to 2010 US dollars using the US
      medical component of the consumer price index (CPI) which may not reflect the
      change in medical costs in other countries. In addition, the costs, in the local
      currency were converted to US dollars in the year of the study. However, medical
      expenses may not vary with exchange rate, leading to artificial variations.
      Finally, there was no assessment of the quality of individual studies, which
      resulted in the same weighting to all studies. CONCLUSIONS: Hepatitis C imposes a
      high economic burden globally. Knowing the burden of HCV sequelae is useful for
      policy decisions as well as serving as a basis for determining the value of HCV
      screening and treatment.

PMID- 22458757
TI  - Recrystallization and reactivation of dopant atoms in ion-implanted silicon
      nanowires.
AB  - Recrystallization of silicon nanowires (SiNWs) after ion implantation strongly
      depends on the ion doses and species. Full amorphization by high-dose
      implantation induces polycrystal structures in SiNWs even after high-temperature
      annealing, with this tendency more pronounced for heavy ions. Hot-implantation
      techniques dramatically suppress polycrystallization in SiNWs, resulting in
      reversion to the original single-crystal structures and consequently high
      reactivation rate of dopant atoms. In this study, the chemical bonding states and
      electrical activities of implanted boron and phosphorus atoms were evaluated by
      Raman scattering and electron spin resonance, demonstrating the formation of p-
      and n-type SiNWs.

PMID- 22458756
TI  - Cost effectiveness of paliperidone palmitate versus risperidone long-acting
      injectable and olanzapine pamoate for the treatment of patients with
      schizophrenia in Sweden.
AB  - OBJECTIVE: To model the cost effectiveness of paliperidone palmitate
      (paliperidone long-acting injectable; PLAI), a new once-monthly long-acting
      antipsychotic therapy, compared with risperidone long-acting injectable (RLAI)
      and olanzapine pamoate (OLAI), in multi-episode patients (two or more relapses)
      with schizophrenia in Sweden. METHODS: A Markov decision analytic model was
      developed to simulate the history of a cohort of multi-episode patients
      transitioning through different health states on a monthly basis over a 5-year
      time horizon from the perspective of the Swedish healthcare system. Therapeutic
      strategies consisted of starting treatment with RLAI (mean dose 37.5 mg every 2
      weeks), PLAI (mean dose 75 mg equivalent (eq.) every month) or OLAI (150 mg every
      2 weeks or 300 mg every 4 weeks). Probability of relapse, level of adherence,
      side-effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and
      diabetes) and treatment discontinuation (switch) were derived from long-term
      observational data when feasible. Incremental cost-effectiveness outcomes,
      discounted at 3% annually, included cost per quality-adjusted life-year (QALY)
      and cost per relapse avoided (expressed in 2009 Swedish Krona SEK). RESULTS:
      Relative to RLAI and OLAI, PLAI is economically dominant: more effective
      (additional QALYs, less relapses) and less costly treatment option over a 5-year
      time horizon. The results were robust when tested in sensitivity analysis.
      LIMITATIONS: The impact of once-monthly treatment on adherence levels is not yet
      known, and not all variables that could impact on real-world outcomes and costs
      were included in this model. CONCLUSION: PLAI was cost saving from a Swedish
      payer perspective compared with RLAI and OLAI in the long-term treatment of multi
      episode (two or more relapses) schizophrenia patients.

PMID- 22458758
TI  - The ceremonial order of public health nursing consultations: an ethnographic
      study.
AB  - AIMS: To explore public health nursing consultations by providing reflections on
      the overt interaction between public health nurses, parents and young people
      during consultations. BACKGROUND: There is limited research on public health
      nursing strategies and intervention models. There is a need to observe and
      describe the content of public health nursing work. DESIGN: The study has an
      ethnographic design and this article focuses mainly on the observations. METHODS:
      Five consultations at four different child health clinics, six consultations at
      two health clinics for young people and one consultation at the school public
      health nurse's office were observed. The sociological concept of role formats
      provides the analytical focus for the paper. RESULTS: There are differences
      between the overriding ceremonial order in the public health nursing
      consultations observed in this study and the dominant role format observed in
      Sociologist P.M. Strong's study of medical consultations. Gentility can be a
      common denominator, yet ease and focus on everyday issues seems consistent with
      public health nursing consultations. The 'personal professional format' seems to
      be the correct term for the overriding ceremonial order. CONCLUSION: The outward
      show of behaviour in nursing and medical consultations differs. Despite society's
      increased bureaucracy within health care systems, ease and a personal
      professional approach, not a rigid bureaucratic format, seems to be the dominant
      ceremonial order in public health nursing consultations. RELEVANCE TO CLINICAL
      PRACTICE: This study is relevant to clinical nursing practice as it can create
      awareness of the taken-for-granted subtleties in nursing consultations. The
      findings show the continued need for supportive universal services that focus on
      the everyday needs of parents, young people and families. The findings also
      reveal the need for further studies on the moral underpinnings of public health
      nursing practice.

PMID- 22458759
TI  - Radiation exposure during nasojejunal intubation for MRI enteroclysis.
AB  - BACKGROUND: Patients with Crohn's disease are often investigated using MRI
      enteroclysis which may provide better visual quality than MRI enterography, but
      exposes patients to radiation. Only few data exist of the radiation dose used in
      fluoroscopy prior to MRI enteroclysis. SUBJECTS AND METHODS: During the 12-month
      study period, all 95 patients (40 men) undergoing MRI enteroclysis with
      nasojejunal intubation using fluoroscopy for suspicion or evaluation of Crohn's
      disease were included. Average age at the time of MRI was 40.1 years (range 17
      79). Conversion factors from dose-area product to effective dose were determined
      with a Monte Carlo-based software PCXMC. The conversion factors were determined
      for a standard-sized adult phantom for posterior-anterior and right-posterior
      oblique projections. RESULTS: The average total time of fluoroscopy was 3 min 17
      s (range 0 min 7 s to 31 min). The average effective dose of ionizing radiation
      was 0.21 mSv (range 0.01-2.67). The average dose is equivalent to 10 PA chest x
      rays. Standard deviation was 0.41 mSv. The highest effective dose of a single
      patient was 2.67 mSv. In comparison, a standard abdominal CT scan causes an
      effective dose of 12 mSv. CONCLUSIONS: The effective dose of ionizing radiation
      with nasojejunal intubation is relatively small in the majority of patients. When
      repeated imaging is necessary, it seems advisable to consider imaging techniques,
      which do not subject patients to ionizing radiation. Also if a previous
      nasojejunal intubation has been difficult, a different imaging technique is
      recommended.

PMID- 22458760
TI  - Valproic acid regulates antioxidant enzymes and prevents ischemia/reperfusion
      injury in the rat retina.
AB  - PURPOSES: To investigate whether valproic acid (VPA) has a neuroprotective effect
      against ischemia/reperfusion (I/R) injury in the rat retina, and to elucidate the
      potential antioxidant mechanisms involved. METHODS: Adult male Wistar rats were
      randomly divided into four groups: sham (group A), sham plus VPA (group B), I/R
      plus vehicle (group C), and I/R plus VPA (group D). Retinal I/R injury was
      produced by inducing an exceedingly high intraocular pressure (IOP). Prior to
      insult, VPA was administered subcutaneously (300 mg/kg twice daily) for 7 days,
      after which the animal was sacrificed. Levels of retinal malondialdehyde (MDA),
      superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)
      were determined. Protein expressions of retinal poly(ADP-ribose) (PAR) and
      nitrotyrosine (NT) were analyzed by Western blotting 24 h after injury. Apoptosis
      of retinal cells was evaluated 24 h after I/R injury by immunofluorescence of
      activated caspase-3 in histological sections of retina. Seven days after
      reperfusion, electroretinography (ERG) was performed, and retinal histological
      changes were examined by light microscopy. RESULTS: Following ischemia, the
      thickness of the entire retina, including the inner nuclear layer (INL) and inner
      plexiform layer (IPL), as well as the number of cells in the ganglion cell layer
      (GCL) were significantly greater in group D than in group C (p < 0.05). VPA
      suppressed I/R-induced reductions in ERG a- and b-wave amplitudes (p < 0.05). VPA
      attenuated I/R-induced activation of caspase-3 in ganglion cells and INL cells (p
      < 0.001). VPA significantly decreased MDA levels and increased activities of SOD,
      GSH-Px, and CAT in group D (p < 0.05). VPA attenuated activation of PAR and
      accumulation of NT in the retina after I/R (p < 0.01). CONCLUSIONS: VPA protects
      the retina from I/R injury by enhancing anti-oxidative effects and inhibiting
      apoptosis of retinal cells.

PMID- 22458761
TI  - Methylphenidate and cocaine self-administration produce distinct dopamine
      terminal alterations.
AB  - Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the
      treatment of attention deficit hyperactivity disorder. MPH has a mechanism of
      action similar to cocaine (COC) and is commonly characterized as a dopamine
      transporter (DAT) blocker. While there has been extensive work aimed at
      understanding dopamine (DA) nerve terminal changes following COC self
      administration, very little is known about the effects of MPH self-administration
      on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core
      slices from animals with a 5-day self-administration history of 40 injections/day
      of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline
      DA release and uptake kinetics as well as alterations in the interaction of each
      compound with the DAT. Although MPH and COC have similar behavioral effects, the
      consequences of self-administration on DA system parameters were found to be
      divergent. We show that COC self-administration reduced DAT levels and maximal
      rates of DA uptake, as well as reducing electrically stimulated release,
      suggesting decreased DA terminal function. In contrast, MPH self-administration
      increased DAT levels, DA uptake rates and DA release, suggesting enhanced
      terminal function, which was supported by findings of increased metabolite/DA
      tissue content ratios. Tyrosine hydroxylase messenger RNA, protein and
      phosphorylation levels were also assessed in both groups. Additionally, COC self
      administration reduced COC-induced DAT inhibition, while MPH self-administration
      increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects
      of these two drugs. These findings suggest that the factors governing DA system
      adaptations are more complicated than simple DA uptake blockade. 

PMID- 22458762
TI  - Overall mortality after radical nephrectomy in patients aged over 80 years with
      renal cancer: a retrospective study on preoperative prognostic factors.
AB  - OBJECTIVES: To evaluate the overall survival postnephrectomy for renal cancer for
      patients aged over 80 years, and to identify preoperative prognostic factors that
      might influence therapeutic strategies. METHODS: In a retrospective study in five
      French departments of urology, 179 patients aged over 80 years with renal cell
      carcinoma underwent radical nephrectomy between 1990 and 2011. The following data
      were collected: age, sex, body mass index, Charlson Comorbidity Index, American
      Society of Anesthesiology class, Eastern Cooperative Oncology Group Performance
      Status, type of surgery, period of follow-up, survival, death etiology, symptoms,
      Fuhrman grade and tumor-nodes-metastasis stage. RESULTS: After a 29.6-month
      follow up, 89 patients (49.7%) died. Death etiologies were: cancer for 46 (52%)
      patients, immediate or distant perioperative complications for five patients (6%)
      and three patients (3%) respectively, cardiovascular disease for 16 patients
      (18%), other cancers for three patients (3%) and unknown for 16 patients (18%).
      In a multivariate analysis, T-stage, M-stage and Charlson Comorbidity Index were
      identified as independent prognostic factors. Patients were divided into three
      groups (good, intermediate and bad prognosis) with significantly different
      survivals of 91, 36 and 22 months (P < 0.0001), respectively. CONCLUSIONS:
      Preoperative data, including T-stage, M-stage and Charlson Comorbidity Index
      represent significant independent prognostic factors for survival for patients
      aged over 80 years. These data might help the clinician in selecting the most
      suitable candidates for radical nephrectomy among elderly patients with renal
      cancer.

PMID- 22458763
TI  - Pyruvate fuels mitochondrial respiration and proliferation of breast cancer
      cells: effect of monocarboxylate transporter inhibition.
AB  - Recent studies have highlighted the fact that cancer cells have an altered
      metabolic phenotype, and this metabolic reprogramming is required to drive the
      biosynthesis pathways necessary for rapid replication and proliferation.
      Specifically, the importance of citric acid cycle-generated intermediates in the
      regulation of cancer cell proliferation has been recently appreciated. One
      function of MCTs (monocarboxylate transporters) is to transport the citric acid
      cycle substrate pyruvate across the plasma membrane and into mitochondria, and
      inhibition of MCTs has been proposed as a therapeutic strategy to target
      metabolic pathways in cancer. In the present paper, we examined the effect of
      different metabolic substrates (glucose and pyruvate) on mitochondrial function
      and proliferation in breast cancer cells. We demonstrated that cancer cells
      proliferate more rapidly in the presence of exogenous pyruvate when compared with
      lactate. Pyruvate supplementation fuelled mitochondrial oxygen consumption and
      the reserve respiratory capacity, and this increase in mitochondrial function
      correlated with proliferative potential. In addition, inhibition of cellular
      pyruvate uptake using the MCT inhibitor alpha-cyano-4-hydroxycinnamic acid
      impaired mitochondrial respiration and decreased cell growth. These data
      demonstrate the importance of mitochondrial metabolism in proliferative responses
      and highlight a novel mechanism of action for MCT inhibitors through suppression
      of pyruvate-fuelled mitochondrial respiration.

PMID- 22458764
TI  - Effect of positive feedback loops on the robustness of oscillations in the
      network of cyclin-dependent kinases driving the mammalian cell cycle.
AB  - The transitions between the G(1), S, G(2) and M phases of the mammalian cell
      cycle are driven by a network of cyclin-dependent kinases (Cdks), whose
      sequential activation is regulated by intertwined negative and positive feedback
      loops. We previously proposed a detailed computational model for the Cdk network,
      and showed that this network is capable of temporal self-organization in the form
      of sustained oscillations, which govern ordered progression through the
      successive phases of the cell cycle [Gerard and Goldbeter (2009) Proc Natl Acad
      Sci USA 106, 21643-21648]. We subsequently proposed a skeleton model for the cell
      cycle that retains the core regulatory mechanisms of the detailed model [Gerard
      and Goldbeter (2011) Interface Focus 1, 24-35]. Here we extend this skeleton
      model by incorporating Cdk regulation through phosphorylation/dephosphorylation
      and by including the positive feedback loops that underlie the dynamics of the
      G(1)/S and G(2)/M transitions via phosphatase Cdc25 and via phosphatase Cdc25 and
      kinase Wee1, respectively. We determine the effects of these positive feedback
      loops and ultrasensitivity in phosphorylation/dephosphorylation on the dynamics
      of the Cdk network. The multiplicity of positive feedback loops as well as the
      existence of ultrasensitivity promote the occurrence of bistability and increase
      the amplitude of the oscillations in the various cyclin/Cdk complexes. By
      resorting to stochastic simulations, we further show that the presence of
      multiple, redundant positive feedback loops in the G(2)/M transition of the cell
      cycle markedly enhances the robustness of the Cdk oscillations with respect to
      molecular noise.

PMID- 22458766
TI  - Effectiveness of TAD-anchored maxillary protraction in late mixed dentition.
AB  - OBJECTIVE: To evaluate the effectiveness of temporary anchorage device (TAD)
      anchored maxillary protraction (MP) in terms of the skeletal and dentoalveolar
      changes and to compare it with traditional tooth-anchored MP. MATERIALS AND
      METHODS: A computerized literature search for relative randomized controlled
      trials and prospective controlled trials was performed in PubMed, MEDLINE,
      Cochrane Central Register of Controlled Trials, Embase, CNKI, and Google Scholar,
      complemented with manual search. Data extraction and quality assessment were
      carried out by two reviewers independently. Meta-analysis was followed when
      possible; otherwise, description was done. RESULTS: Forty articles were found,
      among which four trials were qualified for meta-analysis. The results showed that
      there was significant difference between TAD-anchored MP and untreated control in
      terms of maxillary advancement (weighted mean differences (WMD) 3.08 mm; 95% CI:
      1.61 to approximately 4.56; P < .0001), but there were no consistent points in
      terms of mandibular rotation. Also, there were significant differences between
      both treatment patterns regarding maxillary advancement (WMD 1.41 mm; 95% CI:
      0.47 to approximately 2.35; P  =  .003), mandibular rotation (WMD -1.39 degrees ,
      95% CI: -2.47 to approximately -0.31; P  =  .01), proclination of maxillary
      incisors (WMD -2.29 degrees ; 95% CI: -4.41 to approximately -0.17; P  =  .03),
      and extrusion of maxillary molars (WMD -1.68 mm; 95% CI: -2.51 to approximately 
      0.85; P < .0001). CONCLUSIONS: According to the present results, TAD-anchored MP
      might have a greater maxillary advancement effect and might reduce skeletal and
      dental side effects, compared with tooth-anchored MP.

PMID- 22458768
TI  - Efficacy of additional methotrexate as a maintenance treatment in a Japanese
      patient with psoriatic arthritis refractory to infliximab monotherapy.

PMID- 22458767
TI  - "This does my head in". Ethnographic study of self-management by people with
      diabetes.
AB  - BACKGROUND: Self-management is rarely studied 'in the wild'. We sought to produce
      a richer understanding of how people live with diabetes and why self-management
      is challenging for some. METHOD: Ethnographic study supplemented with background
      documents on social context. We studied a socio-economically and ethnically
      diverse UK population. We sampled 30 people with diabetes (15 type 1, 15 type 2)
      by snowballing from patient groups, community contacts and NHS clinics.
      Participants (aged 5-88, from a range of ethnic and socio-economic groups) were
      shadowed at home and in the community for 2-4 periods of several hours (total 88
      visits, 230 hours); interviewed (sometimes with a family member or carer) about
      their self-management efforts and support needs; and taken out for a meal.
      Detailed field notes were made and annotated. Data analysis was informed by
      structuration theory, which assumes that individuals' actions and choices depend
      on their dispositions and capabilities, which in turn are shaped and constrained
      (though not entirely determined) by wider social structures. RESULTS: Self
      management comprised both practical and cognitive tasks (e.g. self-monitoring,
      menu planning, medication adjustment) and socio-emotional ones (e.g. coping with
      illness, managing relatives' input, negotiating access to services or resources).
      Self-management was hard work, and was enabled or constrained by economic,
      material and socio-cultural conditions within the family, workplace and
      community. Some people managed their diabetes skilfully and flexibly, drawing on
      personal capabilities, family and social networks and the healthcare system. For
      others, capacity to self-manage (including overcoming economic and socio-cultural
      constraints) was limited by co-morbidity, cognitive ability, psychological
      factors (e.g. under-confidence, denial) and social capital. The consequences of
      self-management efforts strongly influenced people's capacity and motivation to
      continue them. CONCLUSION: Self-management of diabetes is physically,
      intellectually, emotionally and socially demanding. Non-engagement with self
      management may make sense in the context of low personal resources (e.g. health
      literacy, resilience) and overwhelming personal, family and social circumstances.
      Success of self-management as a policy solution will be affected by interacting
      influences at three levels: [a] at micro level by individuals' dispositions and
      capabilities; [b] at meso level by roles, relationships and material conditions
      within the family and in the workplace, school and healthcare organisation; and
      [c] at macro level by prevailing economic conditions, cultural norms and
      expectations, and the underpinning logic of the healthcare system. We propose
      that the research agenda on living with diabetes be extended and the political
      economy of self-management systematically studied.

PMID- 22458769
TI  - Consistent mutation status within histologically heterogeneous lung cancer
      lesions.
AB  - AIMS: Activating epidermal growth factor receptor (EGFR) and KRAS mutations
      characterize molecular subgroups of non-small-cell lung cancer (NSCLC) with a
      strong predictive value for response to EGFR inhibitor therapy. However, the
      temporal occurrence and clonal stability of these mutations during the course of
      cancer progression are debated. The aim of this study was to characterize the
      presence of EGFR and KRAS mutations in histologically different areas of primary
      NSCLC lesions. METHODS AND RESULTS: Formalin-fixed paraffin-embedded cancer
      specimens from six cases with EGFR mutations and five cases with KRAS mutations
      were selected from a pool of primary resected NSCLC patients. From each tumour,
      three morphologically distinct areas were manually microdissected and analysed
      for the presence of mutations. The results demonstrated consistent EGFR and KRAS
      mutation status in the different histological areas of all primary tumours.
      CONCLUSION: The results support the concept that activating EGFR and KRAS
      mutations are oncogenic events that are consistently present throughout the
      primary tumour independently of histological heterogeneity. Thus, for molecular
      diagnostics, any part of the tumour is likely to be representative for EGFR and
      KRAS mutation testing.

PMID- 22458771
TI  - Subacute cutaneous lupus erythematosus and its association with drugs: a
      population-based matched case-control study of 234 patients in Sweden.
AB  - BACKGROUND: Numerous case reports about drug-induced (DI) subacute cutaneous
      lupus erythematosus (SCLE) have been published. Various drug types with different
      latencies has been proposed as triggers for this autoimmune skin disease.
      OBJECTIVES: To evaluate the association between exposure to certain suspected
      drugs (previously implicated to induce SCLE) and a subsequent diagnosis of SCLE.
      METHODS: We performed a population-based matched case-control study in which all
      incident cases of SCLE (n=34) from 2006 to 2009 were derived from the National
      Patient Register. The control group was selected from the general population,
      matched (1:10) for gender, age and county of residence. The data were linked to
      the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated for the association between exposures to certain suspected
      drugs and the development of SCLE. RESULTS: During the 6 months preceding SCLE
      diagnosis, 166 (71%) of the patients with SCLE had at least one filled
      prescription of the suspected drugs. The most increased ORs were found for
      terbinafine (OR 52.9, 95% CI 6.6-infinity), tumour necrosis factor-alpha
      inhibitors (OR 8.0, 95% CI 1.6-37.2), antiepileptics (OR 3.4, 95% CI 1.9-5.8) and
      proton pump inhibitors (OR 2.9, 95% CI 2.0-4.0). CONCLUSIONS: We found an
      association between drug exposure and SCLE. More than one third of the SCLE cases
      could be attributed to drug exposure. No significant OR was found for thiazides,
      which might be due to longer latency and therefore missed with this study design.
      DI-SCLE is reversible once the drug is discontinued, indicating the importance of
      screening patients with SCLE for potentially triggering drugs. A causal
      relationship cannot be established from this study and the underlying
      pathogenesis remains unclear.

PMID- 22458772
TI  - Cervical medial branch radiofrequency neurotomy in New Zealand.
AB  - OBJECTIVE: The objective of this study was to determine the effectiveness of
      cervical medial branch radiofrequency neurotomy (RFN) performed by two
      practitioners trained according to rigorous guidelines. DESIGN: The study was
      designed as a prospective, outcome study of consecutive patients with chronic
      neck pain treated in a community setting. INTERVENTIONS: A total of 104 patients,
      selected on the basis of complete relief of pain following controlled,
      diagnostic, medial branch blocks, were treated with RFN according to the
      guidelines of the International Spine Intervention Society. OUTCOME MEASURES:
      Successful outcome was defined as complete relief of pain, or at least 80%
      relief, for at least 6 months, with complete restoration of activities of daily
      living, no need for any further health care, and return to work. Patients who
      failed to meet any of these criteria were deemed to have failed treatment.
      RESULTS: In the two practices, 74% and 61% of patients achieved a successful
      outcome. Relief lasted 17-20 months from the first RFN, and 15 months for repeat
      treatments. Allowing for repeat treatment, patients maintained relief for a
      median duration of 20-26 months, with some 60% still having relief at follow-up.
      CONCLUSION: Cervical RFN can be very effective when performed in a rigorous
      manner in appropriately selected patients. Chronic neck pain, mediated by the
      cervical medial branches, can be temporarily, but completely, relieved and
      patients fully restored to desired activities of daily living, if treated with
      RFN.

PMID- 22458773
TI  - The transcription factor Grainy head and the steroid hormone ecdysone cooperate
      during differentiation of the skin of Drosophila melanogaster.
AB  - The arthropod epidermis is an epithelium that deposits the apical cuticle, which
      is a stratified extracellular matrix (ECM) protecting the animal against
      pathogens, preventing dehydration and also serving as an exoskeleton.
      Differentiation of the cuticle conceivably implies coordinated production,
      secretion and localization of its components. The underlying molecular mechanisms
      are poorly explored. In this work, we show that the transcription factor Grainy
      head and the steroid hormone ecdysone drive the production of two partially
      overlapping sets of cuticle factors. Nevertheless, Grainy head is needed to
      modulate the expression of ecdysone signalling factors; the significance of this
      cross-talk is yet unclear. In addition, we found that ecdysone signalling
      negatively regulates its own impact. In conclusion, our findings suggest that at
      least two independently triggered pathways have evolved in parallel to
      cooperatively ensure the stereotypic implementation of the cuticle. As Grainy
      head is also essential for epithelial differentiation in vertebrates, we
      speculate that it acts to decode the ancient skin programme common to all
      animals. Full differentiation of the skin necessitates a second, complementing
      taxon-specific programme that requires its own decoder, which is represented by
      ecdysone in arthropods, whereas the vertebrate specific one remains to be
      identified.

PMID- 22458774
TI  - A review of the measurement properties of the 36-item short-form health survey
      (SF-36) to determine its suitability for use in an alcohol-dependent population.
AB  - A psychometric evaluation of the 36-item short-form health survey (SF-36) was
      undertaken in contemporary studies to assess its suitability for use in an
      alcohol-dependent population. Three criteria were used to try and determine this:
      factor analysis, internal consistency reliability and test-retest reliability.
      Factor analysis revealed that it is mainly consistent with a bidimensional model,
      internal consistency reliability showed that it consistently provided scores
      above the recommended threshold and test-retest reliability of the SF-36
      highlights that it too provided higher than suggested scores. A conclusion was
      reached recommending the SF-36 as a reliable screening tool in an alcohol
      dependent population, but this is given in caution as no studies were found
      analysing the instrument in this population.

PMID- 22458775
TI  - Complex effects of flavopiridol on the expression of primary response genes.
AB  - BACKGROUND: The Positive Transcription Elongation Factor b (P-TEFb) is a complex
      of Cyclin Dependent Kinase 9 (CDK9) with either cyclins T1, T2 or K. The complex
      phosphorylates the C-Terminal Domain of RNA polymerase II (RNAPII) and negative
      elongation factors, stimulating productive elongation by RNAPII, which is paused
      after initiation. P-TEFb is recruited downstream of the promoters of many genes,
      including primary response genes, upon certain stimuli. Flavopiridol (FVP) is a
      potent pharmacological inhibitor of CDK9 and has been used extensively in cells
      as a means to inhibit CDK9 activity. Inhibition of P-TEFb complexes has potential
      therapeutic applications. RESULTS: It has been shown that Lipopolysaccharide
      (LPS) stimulates the recruitment of P-TEFb to Primary Response Genes (PRGs) and
      proposed that P-TEFb activity is required for their expression, as the CDK9
      inhibitor DRB prevents localization of RNAPII in the body of these genes. We have
      previously determined the effects of FVP in global gene expression in a variety
      of cells and surprisingly observed that FVP results in potent upregulation of a
      number of PRGs in treatments lasting 4-24 h. Because inhibition of CDK9 activity
      is being evaluated in pre-clinical and clinical studies for the treatment of
      several pathologies, it is important to fully understand the short and long term
      effects of its inhibition. To this end, we determined the immediate and long-term
      effect of FVP in the expression of several PRGs. In exponentially growing normal
      human fibroblasts, the expression of several PRGs including FOS, JUNB, EGR1 and
      GADD45B, was rapidly and potently downregulated before they were upregulated
      following FVP treatment. In serum starved cells re-stimulated with serum, FVP
      also inhibited the expression of these genes, but subsequently, JUNB, GADD45B and
      EGR1 were upregulated in the presence of FVP. Chromatin Immunoprecipitation of
      RNAPII revealed that EGR1 and GADD45B are transcribed at the FVP-treatment time
      points where their corresponding mRNAs accumulate. These results suggest a
      possible stress response triggered by CDK9 inhibition than ensues transcription
      of certain PRGs. CONCLUSIONS: We have shown that certain PRGs are transcribed in
      the presence of FVP in a manner that might be independent of CDK9, suggesting a
      possible alternative mechanism for their transcription when P-TEFb kinase
      activity is pharmacologically inhibited. These results also show that the
      sensitivity to FVP is quite variable, even among PRGs.

PMID- 22458776
TI  - Achyranthes aspera enhances immunity and antigen clearance in common carp,
      Cyprinus carpio L.

PMID- 22458777
TI  - Esophageal leiomyoma: experience from a single institution.
AB  - Esophageal leiomyomas are rare. We report the clinicopathologic features of one
      of the largest series of esophageal leiomyomas from a single institution. We
      retrospectively reviewed the Cleveland Clinic pathology database (1985-2010) for
      patients with a diagnosis of esophageal leiomyoma(s). Clinicopathologic features
      of 30 cases from 28 patients were analyzed. The group included 15 females and 13
      males with a mean age at diagnosis of 56 years. These include 9 excisions, 9
      esophagectomies, and 12 endoscopic biopsies. Only one partial esophagectomy was
      performed solely for a symptomatic 14-cm leiomyoma; the remainder of the
      resections (n= 8) were for other indications, including esophageal cancer
      (Barrett's esophagus-related adenocarcinoma and squamous cell carcinoma) and
      emergent esophageal perforation, with leiomyoma being an incidental finding. One
      patient (2.5%) had two synchronous leiomyomas (14 cm and 0.3 cm). Tumor size
      ranged from 0.1 to 14 cm (mean = 2.0 cm). Mean tumor size among symptomatic
      patients was 5.2 cm, as compared with 0.4 cm in asymptomatic patients. Dysphagia
      was the most common complaint in symptomatic patients (71.4%). Sixty-nine percent
      of the tumors were located in the distal and middle thirds of the esophagus, with
      most (69.6%) arising from muscularis propria. Histologically, these tumors were
      composed of bland spindle cells with low cellularity, no nuclear atypia, or
      mitotic activity. Only one case (14 cm) showed focal moderate cellularity and
      nuclear atypia, with low mitotic activity (<1/10 high power field).
      Immunohistochemical studies showed tumor cells were positive for smooth muscle
      actin, and negative for CD34 and CD117. Follow-up information was available for
      22 patients (78.6%), and none had adverse events related to leiomyoma. In
      summary, esophageal leiomyoma is a rare benign tumor of the esophagus. Patients
      with larger tumors were more likely to have symptoms. The majority of the tumors
      were in the lower and mid-esophagus, and arose from muscularis propria. These
      tumors behave in a clinically benign fashion.

PMID- 22458778
TI  - Asexual reproduction induces a rapid and permanent loss of sexual reproduction
      capacity in the rice fungal pathogen Magnaporthe oryzae: results of in vitro
      experimental evolution assays.
AB  - BACKGROUND: Sexual reproduction is common in eukaryotic microorganisms, with few
      species reproducing exclusively asexually. However, in some organisms, such as
      fungi, asexual reproduction alternates with episodic sexual reproduction events.
      Fungi are thus appropriate organisms for studies of the reasons for the selection
      of sexuality or clonality and of the mechanisms underlying this selection.
      Magnaporthe oryzae, an Ascomycete causing blast disease on rice, reproduces
      mostly asexually in natura. Sexual reproduction is possible in vitro and requires
      (i) two strains of opposite mating types including (ii) at least one female
      fertile strain (i.e. a strain able to produce perithecia, the female organs in
      which meiosis occurs). Female-fertile strains are found only in limited areas of
      Asia, in which evidence for contemporary recombination has recently been
      obtained. We induced the forced evolution of four Chinese female-fertile strains
      in vitro by the weekly transfer of asexual spores (conidia) between Petri dishes.
      We aimed to determine whether female fertility was rapidly lost in the absence of
      sexual reproduction and whether this loss was controlled genetically or
      epigenetically. RESULTS: All the strains became female-sterile after 10 to 19
      rounds of selection under asexual conditions. As no single-spore isolation was
      carried out, the observed decrease in the production of perithecia reflected the
      emergence and the invasion of female-sterile mutants. The female-sterile
      phenotype segregated in the offspring of crosses between female-sterile evolved
      strains and female-fertile wild-type strains. This segregation was maintained in
      the second generation in backcrosses. Female-sterile evolved strains were
      subjected to several stresses, but none induced the restoration of female
      fertility. This loss of fertility was therefore probably due to genetic rather
      than epigenetic mechanisms. In competition experiments, female-sterile mutants
      produced similar numbers of viable conidia to wild-type strains, but released
      them more efficiently. This advantage may account for the invasion of our
      populations by female-sterile mutants. CONCLUSIONS: We show for the first time
      that, in the absence of sexual reproduction, female-sterile mutants of M. oryzae
      rice strains can arise and increase in abundance in asexual generations. This
      change in phenotype was frequent and probably caused by mutation. These results
      suggest that female fertility may have been lost rapidly during the dispersion of
      the fungus from Asia to the rest of the world.

PMID- 22458780
TI  - Obtaining the mean relative weights of the cost of care in Catalonia (Spain):
      retrospective application of the adjusted clinical groups case-mix system in
      primary health care.
AB  - OBJECTIVE: The study aims to obtain the mean relative weights (MRWs) of the cost
      of care through the retrospective application of the adjusted clinical groups
      (ACGs) in several primary health care (PHC) centres in Catalonia (Spain) in
      routine clinical practice. METHODS: This is a retrospective study based on
      computerized medical records. All patients attended by 13 PHC teams in 2008 were
      included. The principle measurements were: demographic variables (age and sex),
      dependent variables (number of diagnoses and total costs), and case-mix or co
      morbidity variables (International Classification of Primary Care). The costs
      model for each patient was established by differentiating the fix costs from the
      variable costs. In the bivariate analysis, the Student's t, analysis of variance,
      chi-squared, Pearson's linear correlation and Mann-Whitney-Wilcoxon tests were
      used. In order to compare the MRW of the present study with those of the United
      States (US), the concordance [intraclass correlation coefficient (ICC) and
      concordance correlation coefficient (CCC)] and the correlation (coefficient of
      determination: R2) were measured. RESULTS: The total number of patients studied
      was 227,235, and the frequentation was 5.9 visits/habitant/year) and with a mean
      diagnoses number of 4.5 (3.2). The distribution of costs was ?148.7 million, of
      which 29.1% were fixed costs. The mean total cost per patient/year was ?654.2
      (851.7), which was considered to be the reference MRW. Relationship between study
      MRW and US-MRW: ICC was 0.40 [confidential interval (CI) 95%: 0.21-0.60] and the
      CCC was 0.42 (CI 95%: 0.35-0.49). The correlation between the US MRW and the MRW
      of the present study can be seen; the adjusted R2 value is 0.691. The explanatory
      power of the ACG classification was 36.9% for the total costs. The R2 of the
      total cost without considering outliers was 56.9%. CONCLUSIONS: The methodology
      has been shown appropriate for promoting the calculation of the MRW for each
      category of the classification. The results provide a possible practical
      application in PHC clinical management.

PMID- 22458781
TI  - Structural role of the active-site metal in the conformation of Trypanosoma
      brucei phosphoglycerate mutase.
AB  - Phosphoglycerate mutases (PGAMs) participate in both the glycolytic and the
      gluconeogenic pathways in reversible isomerization of 3-phosphoglycerate and 2
      phosphoglycerate. PGAMs are members of two distinct protein families: enzymes
      that are dependent on or independent of the 2,3-bisphosphoglycerate cofactor. We
      determined the X-ray structure of the monomeric Trypanosoma brucei independent
      PGAM (TbiPGAM) in its apoenzyme form, and confirmed this observation by small
      angle X-ray scattering data. Comparing the TbiPGAM structure with the Leishmania
      mexicana independent PGAM structure, previously reported with a phosphoglycerate
      molecule bound to the active site, revealed the domain movement resulting from
      active site occupation. The structure reported here shows the interaction between
      Asp319 and the metal bound to the active site, and its contribution to the domain
      movement. Substitution of the metal-binding residue Asp319 by Ala resulted in
      complete loss of independent PGAM activity, and showed for the first time its
      involvement in the enzyme's function. As TbiPGAM is an attractive molecular
      target for drug development, the apoenzyme conformation described here provides
      opportunities for its use in structure-based drug design approaches. Database
      Structural data for the Trypanosoma brucei 2,3-bisphosphoglycerate-independent
      phosphoglycerate mutase (iPGAM) has been deposited with the Research
      Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank under code
      3NVL.

PMID- 22458782
TI  - Acne sans P. acnes.
AB  - Acne vulgaris is a common disease that carries an enormous financial and
      psychosocial impact. Androgens, excessive sebum production, ductal
      hypercornification, changes in the microbial flora, as well as inflammation and
      immunological host reactions are considered the major contributors to acne
      pathogenesis. Despite extensive research on acne pathogenesis, the exact sequence
      of events and their possible mechanisms leading to the development of a
      microcomedone and its transformation into an inflamed lesion has remained
      unclear. There is a significant amount of in vitro evidence suggesting a possible
      pathogenetic role for Propionibacterium acnes in comedogenesis as well as
      inflammation in inflammatory acne. However, the microbiological data from non
      inflamed as well as inflamed acne lesions, cultured individually, do not entirely
      support the hypothesis that these micro-organisms are actually responsible for
      their initiation. There appears to be comedones and inflamed lesions in which
      there is no clear evidence of Propionibacterium acnes involvement. Considering
      this microbiological data, alongside the in vitro evidence, we have tried to
      delineate the possible sequence of events and their mechanisms, leading to the
      development of a microcomedone and its transformation into an inflamed lesion.
      Based on the available literature we have analysed the evidence of both non
      inflamed as well as inflamed acne lesions occurring in the absence of
      Propionibacterium acnes from the pilosebaceous follicles. We propose that the
      development of an inflamed acne lesion depends on an imbalance between the pro
      inflammatory and anti-inflammatory pathways rather than the incitement of
      inflammation by Propionibacterium acnes.

PMID- 22458779
TI  - Real-time sensing and discrimination of single chemicals using the channel of
      phi29 DNA packaging nanomotor.
AB  - A highly sensitive and reliable method to sense and identify a single chemical at
      extremely low concentrations and high contamination is important for
      environmental surveillance, homeland security, athlete drug monitoring,
      toxin/drug screening, and earlier disease diagnosis. This article reports a
      method for precise detection of single chemicals. The hub of the bacteriophage
      phi29 DNA packaging motor is a connector consisting of 12 protein subunits
      encircled into a 3.6 nm channel as a path for dsDNA to enter during packaging and
      to exit during infection. The connector has previously been inserted into a lipid
      bilayer to serve as a membrane-embedded channel. Herein we report the
      modification of the phi29 channel to develop a class of sensors to detect single
      chemicals. The lysine-234 of each protein subunit was mutated to cysteine,
      generating 12-SH ring lining the channel wall. Chemicals passing through this
      robust channel and interactions with the SH group generated extremely reliable,
      precise, and sensitive current signatures as revealed by single channel
      conductance assays. Ethane (57 Da), thymine (167 Da), and benzene (105 Da) with
      reactive thioester moieties were clearly discriminated upon interaction with the
      available set of cysteine residues. The covalent attachment of each analyte
      induced discrete stepwise blockage in current signature with a corresponding
      decrease in conductance due to the physical blocking of the channel. Transient
      binding of the chemicals also produced characteristic fingerprints that were
      deduced from the unique blockage amplitude and pattern of the signals. This study
      shows that the phi29 connector can be used to sense chemicals with reactive
      thioesters or maleimide using single channel conduction assays based on their
      distinct fingerprints. The results demonstrated that this channel system could be
      further developed into very sensitive sensing devices.

PMID- 22458783
TI  - An ex vivo model for suture-less amniotic membrane transplantation with a
      chemically defined bioadhesive.
AB  - PURPOSE: Chemically defined bioadhesives (CDB) are "two-component reactive
      adhesives" made from antibiotic food additives. They contain no animal-derived
      ingredients and are characterized by a high level of self-degradability, low
      toxicity, and strong bonding properties. Amniotic membrane (AM) transplantation
      is used to repair severe ocular surface disease in humans and horses. AM requires
      meticulous suturing to the injured cornea. The purpose of this study is to
      determine whether CDB can facilitate the suture-less placement and adherence of
      equine AM to porcine cadaver cornea. DESIGN: Prospective study. MATERIALS AND
      METHODS: To determine whether there are differences in ex vivo adhesion force
      between equine AM bonded with CDB to porcine cadaver cornea and equine AM sutured
      to porcine cadaver cornea. The following groups were tested (n = 5 per group):
      (1) CDB group: trephined (8 mm in diameter) cornea was bonded with CDB to 8-mm
      sized discs of AM. (2) Suture group: the 8-mm trephined cornea was sutured with 8
      0 absorbable suture to the AM. (3) Control group 1: two sheets of nitrocellulose
      paper were bonded with CDB. (4) Control group 2: two sheets of nitrocellulose
      paper were attached with suture and tested. Each sample was anchored to a
      tensiometer materials testing machine, and the strength of adhesion measured and
      expressed in units of kilogram-force (kgf). RESULTS: Mean +/- SD strength of
      adhesion force found no statistically significant difference between CDB group
      (0.091 +/- 0.054 kgf; 15 min of CDB adhesion time) and suture groups (0.095 +/-
      0.037 kgf), whereas there was significant difference (P < 0.05) between control
      group 1 (0.679 +/- 0.048 kgf) and control group 2 (0.585 +/- 0.092 kgf). These
      results revealed that the 15 min of CDB adhesive time had adhesive properties as
      strong as suture group. CONCLUSIONS AND CLINICAL RELEVANCE: CDB provides a
      satisfactory level of adherence to ex vivo suture-less attachment of equine
      amniotic membrane transplantation to the porcine cornea.

PMID- 22458784
TI  - Reducing drink driving in low- and middle-income countries: challenges and
      opportunities.
AB  - A great deal of progress has been made in reducing alcohol-impaired driving
      crashes and the related injuries and deaths in countries around the world.
      Unfortunately, this progress has not been shared by many low- and middle-income
      countries. In response to this disparity, a variety of international efforts have
      been undertaken, including the Drink Driving Initiative of Global Actions on
      Harmful Drinking, being carried out with a focus on 6 low- and middle-income
      countries where drink driving is a significant issue. These countries are China,
      Colombia, Mexico, Nigeria, Russia, and Vietnam. This article provides an overview
      of situational assessments that describe the current drink driving problems in
      these countries and the laws, policies, enforcement efforts, and public attitudes
      related to drink driving. These descriptions show clearly that there are
      particular challenges faced by the countries discussed here. Some, such as a lack
      of reliable traffic safety data, are common to most of the countries. This lack
      of data may be interrelated with the lack of well-developed drink driving
      policies. Other challenges vary depending on the particular geographic, economic,
      cultural, and social situations in each country. The assessments indicate the
      need for a focus on capacity building at the organizational and individual level
      in the target countries. The assessments also indicate that a long-term
      commitment to strengthening policies, implementation, and evaluation will be
      needed. This deeper understanding of the situations in each of these countries is
      already being put to use in what we hope is the beginning of an important and
      lifesaving process.

PMID- 22458785
TI  - Assessing a country's drink driving situation: an overview of the method used in
      6 low- and middle-income countries.
AB  - The International Center for Alcohol Policies (ICAP) has developed an
      international program to reduce drink driving as part of its strategy for Global
      Actions on Harmful Drinking. The program focuses on capacity building, training,
      and the implementation, monitoring, and evaluation of regional and local pilot
      projects in 6 participating low- and middle-income countries. The first step in
      developing an effective program that addresses specific problems in a region or
      country is to assess the current drink driving situation. In order to meet this
      key requirement, ICAP developed a situation assessment approach based largely on
      the recommendations of Chapter 2 of the good practice manual on drinking and
      driving produced by the Global Road Safety Partnership (GRSP) under the auspices
      of the United Nations (UN) Road Safety Collaboration. The aim of the assessment
      was to provide the foundation for preparing a prioritized and effective suite of
      projects using the good practice recommended by the GRSP/UN manual. Its output is
      intended to assist with determining program objectives, design, and evaluation so
      that the benefits from the investments in drink driving programs can be maximized
      and data led, focusing on the priorities identified by the assessment. The
      situation assessment approach was produced as a set of guidelines containing a
      detailed and structured list of questions. The questions are organized into 6
      main groups or elements and they enable a comprehensive and systematic collection
      of existing information about the extent and nature of the drink driving problem,
      the strengths and weaknesses of the current prevention practices, and the
      capacity for improvements. Situation assessments using these guidelines have been
      completed in the 6 focus countries and the resulting information is now being
      used for capacity building and developing appropriate and relevant pilot
      projects, taking into consideration the country's culture with respect to
      transportation, enforcement, health care, and alcohol consumption.

PMID- 22458786
TI  - The drink driving situation in China.
AB  - OBJECTIVE: China has been concerned about the serious problem of drinking and
      driving road crashes, and it has made good progress by establishing strict laws,
      imposing serious penalties, and initiating a rigorous enforcement program since
      2008. This study has assessed the magnitude and nature of the problem and
      reviewed the legislation, current practices, and institutional capacities for
      preventing drinking and driving. METHODS: Data and information were collected
      using existing reports and by consulting officials and experts from a number of
      agencies. RESULTS: Although there were no national statistics on levels of
      drinking and driving, random breath test surveys in 2 southern cities showed that
      between 4.5 and 4.6 percent of drivers were driving over the minimum legal blood
      alcohol concentration (BAC) limit of 20 mg/100 mL. Preliminary results from crash
      data also showed that at least 20 percent of serious road crashes were alcohol
      related in these cities. The national published figure for fatal crashes caused
      by drinking and driving was much lower, only 4 percent, but alcohol was not often
      identified as the main cause because of measurement difficulties. China's
      legislation sets 2 BAC limits that are comparable with international norms. It
      has recently increased the penalties for drunk driving, the more serious of the 2
      offenses, with a minimum driving ban of 5 years. The police are actively
      enforcing the laws through frequent roadside checking but they need more
      resources. Alcohol breath tests before and after a combined publicity and
      enforcement campaign indicated reductions of 87 and 68 percent of drivers over
      the legal limit in 2 southern cities. CONCLUSIONS: China has made progress in
      strengthening its approach to preventing drinking and driving, particularly in
      the area of law enforcement. However, it is not possible to evaluate the
      potential benefits because of data issues. Recommendations for the future include
      the need to improve the national road crash and injury database, strengthen the
      coordination of key agencies, and provide more effective and sustained public
      information campaigns that target vulnerable drivers and are integrated with
      enforcement strategies. Evaluation and research are important to improve future
      prevention programs.

PMID- 22458787
TI  - The drink driving situation in Vietnam.
AB  - OBJECTIVE: To identify the extent and nature of the problem and the main
      contributing factors to drink driving crashes; determine the current mechanisms
      in place, particularly in terms of legislation and its enforcement; and identify
      baseline data and relevant stakeholders. METHODS: The situational assessment was
      based on the collection of secondary data from available reports and documents,
      in-depth interviews with key representatives at a central level, and field
      surveys in provinces. RESULTS: Vietnam has experienced phenomenal growth in motor
      vehicles, especially motorcycles, in the last decade (400%). This initially led
      to an increase in deaths from road crashes, but since 2006 the number has stayed
      fairly level according to police statistics. However, comparisons with health
      data suggest that the number of deaths is much higher and there are clearly a
      number of problems with the relevant data systems. Data on the percentage of
      drivers exceeding legal limits are not available, but police statistics indicated
      that drinking alcohol was a contributory factor in 7 percent of motor vehicle
      crashes. This is likely to be an underestimate, because the police and health
      services do not have the equipment to measure the blood alcohol concentration
      (BAC) levels of all drivers in crashes. Motorcycle riders and young people are in
      the high-risk groups. There are strict BAC limits starting at over zero and
      severe punishments for drunk drivers involved in serious crashes. However, the
      police do not have adequate manpower or equipment to conduct regular and frequent
      roadside checking for drivers who have been drinking. There have also been a
      number of education programs on road safety including drinking and driving, but
      these have not included sustained and intensive campaigns targeting the high-risk
      groups. The National Traffic Safety Committee (NTSC) is responsible for
      coordinating the relevant agencies but there is still a problem with lack of
      information sharing between agencies. CONCLUSIONS: This study completed a
      comprehensive situational assessment that examined the problem of drinking and
      driving and identified some of the weaknesses in the current prevention system.
      Vietnam currently has 2 international projects on road safety and it is hoped
      that these together with support from the International Center for Alcohol
      Policies (ICAP) Global Actions program will provide opportunities for
      strengthening drinking and drive prevention initiatives by improving the road
      crash and injury database, building the capacity of the key organizations,
      strengthening the coordination mechanisms, and implementing and evaluating trial
      drink-drive interventions.

PMID- 22458788
TI  - The drink driving situation in Nigeria.
AB  - OBJECTIVE: This study was carried out to assess the magnitude and nature of the
      drink-drive problem in Nigeria and evaluate the institutional capacities for
      preventing drinking and driving, using the methodology developed by the
      International Center for Alcohol Policies (ICAP) described in the overview
      article in this issue (Johnson 2012). METHODS: Data and information were
      collected using existing reports and by consulting officials and experts from a
      number of key agencies. RESULTS: In 2008, 9572 people died in road crashes
      according to police statistics. However, according to World Health Organization
      statistical modeling, this figure is likely to be much higher, with deaths
      ranging from 34,000 to 78,000 in 2007 and a mortality rate of 32.3 percent. Not
      only is it likely that the police data underestimate the road crash problem but
      it was also found that the data from the police and the Federal Road Safety
      Commission (FRSC) were inadequate for estimating the extent of the drink-drive
      problem mainly because of the lack of alcohol testing equipment. One research
      study highlighted the problem of drivers of commercial vehicles; 67.2 percent of
      drivers admitting to drinking alcohol during the working day. Nigeria sets a
      legal limit of 0.05 g/100 mL blood alcohol concentration (BAC), but enforcement
      of the law is weak because alcohol testing equipment is unavailable. The FRSC is
      a federal agency dedicated to improving road safety and the clear lead agency in
      Nigeria. It runs publicity campaigns against drinking and driving with private
      sector support, especially toward the end of the year when there is increased
      vehicular traffic due to people travelling to celebrate the Christmas and New
      Year holidays, but these have not been evaluated. However, its combined
      enforcement and public education roles give it considerable potential for
      tackling the drink-drive problem in the future. CONCLUSIONS: This study
      recommended that priority should be given to strengthening the road crash and
      injury database and drink-drive enforcement, especially for drivers of commercial
      vehicles, and that the opportunities provided by the World Bank project
      supporting safe road corridors should be maximized.

PMID- 22458789
TI  - The drink driving situation in Colombia.
AB  - OBJECTIVE: To describe and analyze the drink driving situation in Colombia.
      METHODS: The assessment was based on semistructured interviews of key
      stakeholders and analysis of secondary data. RESULTS: Road traffic crashes caused
      5704 deaths and injured 39,318 people in 2010. The 3 main sources of crash data
      forensic authorities, traffic authorities, and motor vehicle insurance agencies
      provide different information about crashes, drivers, and victims, but they
      cannot be routinely merged. This together with the problem of identifying alcohol
      as the cause of a crash makes it difficult to estimate the role of drink driving
      in road crashes. In addition, reliable figures for the incidence of drink driving
      are not available from the random breath test programs because of sampling
      issues, underreporting, and missing data on negative results. However, it can be
      argued that alcohol plays a role in fatalities, because the proportion of crashes
      involving fatalities rises on weekends and between 12:00 a.m. and 05:59 a.m. when
      drink driving is likely to occur. Colombia has strict drink-drive laws that
      specify 3 levels of offense and sanctions (level I: 40- 99 mg/100 mL, level II:
      100-149 mg/100 mL, and level III: 150 mg/100 mL or above). Drivers responsible
      for causing crashes with fatalities and injuries can be imprisoned under criminal
      law and sentences are increased by 50 to 100 percent if they test positive for
      alcohol. Enforcement includes random breath testing for alcohol, but its impact
      is weakened by the lack of a legal requirement to submit to a test and poor
      implementation of sanctions. There have been mass media campaigns against drink
      driving including one linked to a major enforcement initiative in 2008. However,
      there was a consensus that most campaigns were not focused sufficiently on
      increasing drivers' perceived risk of being caught. According to those
      interviewed, campaigns aimed at responsible consumption and the use of designated
      drivers appear to have had a growing positive effect, but these impacts have not
      been empirically assessed. The Road Prevention Fund is a Sui Generis institution
      in Colombia that has played a key role in tackling the drink driving problem.
      CONCLUSIONS: Legal blood alcohol concentration (BAC) limits are on a par with
      international standards and the traffic authorities carry out regular roadside
      sobriety checks. However, the enforcement is weakened by poor implementation of
      sanctions. In addition, issues with data mean that the nature and extent of drink
      driving in Colombia cannot be accurately monitored.

PMID- 22458790
TI  - Recent changes in the age composition of drivers in 15 countries.
AB  - OBJECTIVE: This study examined the recent changes in the percentage of persons
      with a driver's license in 15 countries as a function of age. METHOD: The
      countries included were Canada, Finland, Germany, Great Britain, Israel, Japan,
      Latvia, The Netherlands, Norway, Poland, South Korea, Spain, Sweden, Switzerland,
      and the United States. RESULTS: The results indicate 2 patterns of change over
      time. In one pattern (observed for 8 countries), there was a decrease in the
      percentage of young people with a driver's license, and an increase in the
      percentage of older people with a driver's license. In the other pattern
      (observed for the other 7 countries), there was an increase in the percentage of
      people with a driver's license in all age categories. A regression analysis was
      performed on the data for young drivers in the 15 countries to explore the
      relationship between licensing and a variety of societal parameters. Of
      particular note was the finding that a higher proportion of Internet users was
      associated with a lower licensure rate. IMPLICATIONS: The results of the analysis
      are consistent with the hypothesis that access to virtual contact reduces the
      need for actual contact among young people.

PMID- 22458791
TI  - Does personality predict driving performance in middle and older age? An evidence
      based literature review.
AB  - OBJECTIVE: To conduct a literature review of the relationship between personality
      and driving performance among middle-aged and older adults. METHODS: We searched
      for relevant literature using Web of Science, PsycInfo, and PubMed and consulted
      with experts for recently published literature not yet catalogued in those
      databases. Using the American Academy of Neurology's classification criteria, we
      extracted data from 13 studies and assigned a class (I-IV) to each study. We
      grouped primary studies into 3 main categories of driving assessment (behavioral
      assessment: comprehensive driving evaluations, alternative on-road driving
      evaluations, driving simulations; automobile crashes: state-recorded crashes,
      self-reported crashes; self-report measures: self-reported driving behaviors). In
      all, we synthesized the relationship between personality and driving performance
      for middle-aged and older adults. RESULTS: To assist clinicians and researchers
      in future considerations of the relationship between personality and driving
      performance, we provide specific evidence-based recommendations for several
      driving assessments: on-road driving evaluations (Level B), driving simulations
      (Level U), state-recorded crashes (Level C), self-reported crashes (Level C), and
      self-reported driving behaviors (Level C). CONCLUSIONS: Overall, we found
      evidence for personality as a reliable predictor of driving performance among
      older drivers. However, 2 caveats qualify our conclusions: the research
      considered only a limited number of personality variables and largely consisted
      of less valid tests of driving performance. Therefore, to truly understand the
      relationship between personality and driving performance, future research must
      consider a wider range of individual differences and employ more stringent tests
      and methodological designs to measure driving performance.

PMID- 22458793
TI  - Impact of age, location, and bicycle style on helmet usage by adults.
AB  - OBJECTIVE: Our objective was to describe current patterns of bicycle helmet usage
      in a university community using a direct observation approach. PARTICIPANTS:
      Cyclists in a university community observed in 2010 and 2011. METHODS: We
      identified 6 locations in Athens, Georgia, and recorded the type of bicycle, age
      group, sex, and helmet usage of passing cyclists. We performed univariate and
      multivariate analysis to identify independent predictors of helmet usage.
      RESULTS: We observed 433 cyclists: 74 percent male, 74 percent college age, and
      45 percent of whom wore a helmet. Helmet usage varied by bicycle type, location
      of observation, and age group. Independent predictors of bike helmet were on
      campus location (0.38, 95% confidence interval [CI]: 0.22-0.66), college-age
      rider (0.29, 95% CI: 0.15-0.54), and use of a city or leisure bike (0.39, 95% CI:
      0.23-0.65). CONCLUSIONS: College-age riders, riders on campus, and those riding a
      city or leisure-style bike are less likely to wear a helmet. Health promotion
      efforts aimed at increasing helmet usage should target these groups.

PMID- 22458792
TI  - Costs associated with helmet use in motorcycle crashes: the cost of not wearing a
      helmet.
AB  - OBJECTIVE: The relationship between injuries sustained in a motorcycle crash
      (MCC) by unhelmeted motorcyclists and the multitude of costs associated with
      those injuries has been a decades-long debate. Results from research addressing
      injuries and mortality due to helmet use in MCCs demonstrates that unhelmeted
      motorcyclists experience more severe injuries, resulting in higher health care
      costs and an increased likelihood of requiring care beyond the hospital in other
      facilities. However, a link between injury severity and hospital costs has not
      been established with its spillover effect onto health insurance providers. This
      retrospective study was designed to delineate the health care and insurance costs
      of adult trauma patients admitted to a Level 1 trauma center due to an MCC.
      METHODS: The study included adult trauma patients 18 years of age or older
      admitted to a Level 1 trauma center due to an MCC between January 1, 2005, and
      December 31, 2010. The center is a receiving hospital for the central third of a
      Midwestern state, serving a medium-sized city as well as rural and isolated
      population areas. Patients were stratified into 2 groups based on helmet use.
      Patient variables included mechanism of injury, clinical characteristics, total
      units of blood used, intensive care unit (ICU) length of stay (LOS), hospital
      LOS, days on a ventilator, mortality, number of procedures during hospital stay,
      primary payor, discharge location, and total hospital charges. A linear
      regression model was used to predict the charges associated with the severity of
      injuries. RESULTS: A significant difference was found for total hospital charges.
      The mean total hospital charge for helmeted patients was $4184.26 compared to
      $7383.31 for unhelmeted patients. The prediction model was statistically
      significant, indicating that not wearing a helmet starts the patient at a cost of
      $3199.06. The cost of treatment for patients who wore helmets was $256.93 for
      each incremental increase in Injury Severity Score (ISS) compared to $537.57 for
      unhelmeted patients. ICU LOS, hospital LOS, and vent days were statistically
      significant, with durations longer for unhelmeted patients. Helmeted patients
      also required more units of blood. The total number of procedures for each
      patient approached significance, with the unhelmeted group requiring more
      procedures. CONCLUSIONS: The goal of the study was to delineate the medical costs
      associated with helmet use and nonuse in motorcyclists. The results demonstrate
      that medical costs due to an MCC for an unhelmeted motorcyclist were
      significantly higher than for a helmeted motorcyclist. These costs were paid by
      providers of health insurance, mainly Civilian Health and Medical Program of the
      Uniformed Services (CHAMPUS), Medicaid, and commercial insurance.

PMID- 22458794
TI  - Risk factors in motorcyclist fatalities in Taiwan.
AB  - OBJECTIVE: To assess the impact of the following factors on rider fatality:
      rider's age, gender, licensing status, accident liability, use of helmet, alcohol
      consumption, vehicle class, road conditions, presence of passengers, and
      passenger injuries. METHODS: Data on motorcycle accidents in Taiwan between 2006
      and 2008 were analyzed. A logistic regression model was used to establish a
      fatality risk model for motorcyclists and investigate high-risk factors for
      motorcyclist fatality. RESULTS: Higher fatality rates among motorcycle riders
      correlate with the following factors: male, older, unlicensed, not wearing a
      helmet, riding after drinking, and driving heavy (i.e., above 550 cc)
      motorcycles. In addition, motorcyclists involved in nighttime, nonurban single
      vehicle accidents have a higher risk of death, and lone riders have a higher risk
      of death in accidents than do riders carrying passengers. The seriousness of
      passenger injury also correlates positively with the rider's risk of death.
      CONCLUSIONS: Nearly 60 percent of all driving fatalities in Taiwan involve
      motorcycles. Consideration of factors behind the high frequency and risk of
      motorcycle deaths, specifically rider age above 60 years, not wearing a
      motorcycle helmet, riding after drinking, and driving without a valid license,
      could help in the development of effective traffic safety management measures.

PMID- 22458795
TI  - Kinematics of the unrestrained vehicle occupants in side-impact crashes.
AB  - A test series involving direct right-side impact of a moving wall on unsupported,
      unrestrained cadavers with no arms was undertaken to better understand human
      kinematics and injury mechanisms during side impact at realistic speeds. The
      tests conducted provided a unique opportunity for a detailed analysis of the
      kinematics resulting from side impact. Specifically, this study evaluated the 3
      dimensional (3D) kinematics of 3 unrestrained male cadavers subjected to lateral
      impact by a multi-element load wall carried by a pneumatically propelled rail
      mounted sled reproducing a conceptual side crash impact. Three translations and 3
      rotations characterize the movement of a solid body in the space, the 6 degrees
      of freedom (6DoF) kinematics of 15 bone segments were obtained from the 3D marker
      motions and computed tomography (CT)-defined relationships between the maker
      array mounts and the bones. The moving wall initially made contact with the
      lateral aspect of the pelvis, which initiated lateral motion of the spinal
      segments beginning with the pelvis and moving sequentially up through the lumbar
      spine to the thorax. Analyzing the 6DoF motions kinematics of the ribs and
      sternum followed right shoulder contact with the wall. Overall thoracic motion
      was assessed by combining the thoracic bone segments as a single rigid body. The
      kinematic data presented in this research provides quantified subject responses
      and boundary condition interactions that are currently unavailable for lateral
      impact.

PMID- 22458796
TI  - Head impact contact points for restrained child occupants.
AB  - OBJECTIVE: Head injuries are the most common injuries sustained by children in
      motor vehicle crashes regardless of age, restraint, and crash direction. For rear
      seat occupants, the interaction of the subject with the seat back and the vehicle
      side interior structures has been previously highlighted. In order to advance
      this knowledge to the development of countermeasures, a summary of vehicle
      components that contributed to these injuries is needed. Therefore, the objective
      of this study was to create a contact map of the vehicle interior for head and
      face injuries to rear-seated restrained children in front crashes. METHODS: The
      Crash Injury Research and Engineering Network (CIREN) was queried for rear
      seated, restrained child occupants (age 0-15 years) in forward-facing child
      restraints, booster seats, or lap and shoulder belts who sustained an AIS2+ head
      and/or face injury in a frontal motor vehicle crash. Cases were analyzed to
      describe injury patterns and injury causation scenarios. A contact point map was
      developed to summarize the vehicle components related to injury causation of the
      head/face injury. RESULTS: Twenty-one cases met the combined inclusion and
      exclusion criteria. Seven of the child occupants were restrained in forward
      facing child restraints, 2 in belt-positioning booster seats, and 12 in lap and
      shoulder belts. There were 28 head and 17 facial injuries. For left rear
      occupants, the most common contact point was the pillar in front of the
      occupant's seat row; that is, B-pillar for second-row occupants, indicating a
      leftward kinematics. For right rear occupants, due to differences in crash
      dynamics, the most common contact point location was the passenger's seat back,
      suggesting that these occupants moved predominantly forward. CONCLUSIONS: Contact
      points associated with head/face injury for restrained children 0 to 15 years in
      frontal crashes have been delineated. In a majority of the cases, the head/face
      injury was the most severe injury and severe injuries to other body regions were
      uncommon, suggesting that efforts to mitigate head injuries for these occupants
      would greatly improve their overall safety. The majority of the head/face contact
      points were to the first row seat back and B-pillar. In these frontal crashes,
      the importance of head/face contact with the vehicle side structure suggests that
      deploying a curtain air bag in frontal impacts may help manage the energy of
      impact. These data advance the current understanding of injury patterns and
      causation in frontal crashes involving restrained rear-row occupants and can be
      used to develop solutions to mitigate the injuries sustained.

PMID- 22458797
TI  - Parameter study for child injury mitigation in near-side impacts through FE
      simulations.
AB  - OBJECTIVE: The objective of this study is to investigate the effects of crash
      related car parameters on head and chest injury measures for 3- and 12-year-old
      children in near-side impacts. METHODS: The evaluation was made using a model of
      a complete passenger car that was impacted laterally by a barrier. The car model
      was validated in 2 crash conditions: the Insurance Institute for Highway Safety
      (IIHS) and the US New Car Assessment Program (NCAP) side impact tests. The Small
      Side Impact Dummy (SID-IIs) and the human body model 3 (HBM3) (Total HUman Model
      for Safety [THUMS] 3-year-old) finite element models were used for the parametric
      investigation (HBM3 on a booster). The car parameters were as follows: vehicle
      mass, side impact structure stiffness, a head air bag, a thorax-pelvis air bag,
      and a seat belt with pretensioner. The studied dependent variables were as
      follows: resultant head linear acceleration, resultant head rotational
      acceleration, chest viscous criterion, rib deflection, and relative velocity at
      head impact. The chest measurements were only considered for the SID-IIs.
      RESULTS: The head air bag had the greatest effect on the head measurements for
      both of the occupant models. On average, it reduced the peak head linear
      acceleration by 54 g for the HBM3 and 78 g for the SID-IIs. The seat belt had the
      second greatest effect on the head measurements; the peak head linear
      accelerations were reduced on average by 39 g (HBM3) and 44 g (SID-IIs). The high
      stiffness side structure increased the SID-IIs' head acceleration, whereas it had
      marginal effect on the HBM3. The vehicle mass had a marginal effect on SID-IIs'
      head accelerations, whereas the lower vehicle mass caused 18 g higher head
      acceleration for HBM3 and the greatest rotational acceleration. The thorax-pelvis
      air bag, vehicle mass, and seat belt pretensioner affected the chest measurements
      the most. The presence of a thorax-pelvis air bag, high vehicle mass, and a seat
      belt pretensioner all reduced the chest viscous criterion (VC) and peak rib
      deflection in the SID-IIs. CONCLUSIONS: The head and thorax-pelvis air bags have
      the potential to reduce injury measurements for both the SID-IIs and the HBM3,
      provided that the air bag properties are designed to consider these occupant
      sizes also. The seat belt pretensioner is also effective, provided that the
      lateral translation of the torso is managed by other features. The importance of
      lateral movement management is greater the smaller the occupant is. Light
      vehicles require interior restraint systems of higher performance than heavy
      vehicles do to achieve the same level of injury measures for a given side
      structure.

PMID- 22458798
TI  - A geographic analysis of collisions involving child pedestrians in a large
      Southern California county.
AB  - OBJECTIVES: The goal of this study is to explore the relationship between child
      pedestrian injuries and socioeconomic characteristics of neighborhoods in the
      context of local traffic volume. METHODS: Child pedestrian collisions were
      identified in the data of the California Statewide Integrated Traffic Records
      System (SWITRS). Nine hundred sixty crashes over a 5-year period were identified,
      geocoded, and mapped to Orange County census tracts. Census data from 2000 were
      used to identify tracts, population, and population characteristics in the county
      of approximately 3,000,000 individuals. Pedestrian collision maps were merged
      with census characteristics and analyzed using STATA (Version 10.1, Stata Corp,
      College Station, IX) to determine correlations between socioeconomic factors and
      collision rates within census tracts. RESULTS: The percentage of the population
      living in households with low income (less than 185% of the federal poverty
      level) was the strongest predictor of pedestrian injuries. One fourth of census
      tracts had less than 9 percent of residents with low income and averaged 6 per
      100,000 child pedestrian crashes annually. One fourth of the census tracts had
      more than 32 percent of residents with low income and an average of 56 child
      pedestrian crashes per 100,000 annually. These data indicate an 8.8-fold increase
      in collision frequency in the lowest income quartile over the highest income
      quartile. Other socioeconomic correlates strongly associated with increased child
      collisions include population density, proportion of population speaking English
      less than very well, lack of high school education, number of multifamily
      residences, and Latino ethnicity. CONCLUSIONS: Our study showed that child
      pedestrian collisions are nearly 9 times more frequent in the poorest quartile of
      neighborhoods than in the richest quartile. Other factors associated with
      increased pediatric collision risk include increased neighborhood crowding, low
      levels of education and English speaking ability, and Latino ethnicity.

PMID- 22458799
TI  - Safety evaluation of joint and conventional lane merge configurations for freeway
      work zones.
AB  - Inefficient operation of traffic in work zone areas not only leads to an increase
      in travel time delays, queue length, and fuel consumption but also increases the
      number of forced merges and roadway accidents. This study evaluated the safety
      performance of work zones with a conventional lane merge (CLM) configuration in
      Louisiana. Analysis of variance (ANOVA) was used to compare the crash rates for
      accidents involving fatalities, injuries, and property damage only (PDO) in each
      of the following 4 areas: (1) advance warning area, (2) transition area, (3) work
      area, and (4) termination area. The analysis showed that the advance warning area
      had higher fatality, injury, and PDO crash rates when compared to the transition
      area, work area, and termination area. This finding confirmed the need to make
      improvements in the advance warning area where merging maneuvers take place.
      Therefore, a new lane merge configuration, called joint lane merge (JLM), was
      proposed and its safety performance was examined and compared to the conventional
      lane merge configuration using a microscopic simulation model (VISSIM), which was
      calibrated with real-world data from an existing work zone on I-55 and used to
      simulate a total of 25 different scenarios with different levels of demand and
      traffic composition. Safety performance was evaluated using 2 surrogate measures:
      uncomfortable decelerations and speed variance. Statistical analysis was
      conducted to determine whether the differences in safety performance between both
      configurations were significant. The safety analysis indicated that JLM
      outperformed CLM in most cases with low to moderate flow rates and that the
      percentage of trucks did not have a significant impact on the safety performance
      of either configuration. Though the safety analysis did not clearly indicate
      which lane merge configuration is safer for the overall work zone area, it was
      able to identify the possibly associated safety changes within the work zone area
      under different traffic conditions.

PMID- 22458800
TI  - Analysis of deaths caused by pat-pat accidents in Turkey.
AB  - This study deals with deaths during the period 2004 to 2009 that occurred during
      the use of a vehicle known as pat-pat, which is an unusual vehicle, similar to a
      tractor-trailer used in agricultural production and transportation     The
      records of crime scene investigation and autopsies of 28 cases of death due to
      pat-pat-related crushes were evaluated. Of all cases, 60.7 percent were drivers
      and the remaining 39.3% were passengers. The most common cause of death (in 39.3%
      of cases) was brain-spinal cord injury due to blunt trauma of the head and neck.
      Implementing legislation regarding safety measures or limitation of the use for
      transportation should be performed for pat-pats, of which thousands are currently
      in use.

PMID- 22458801
TI  - Determining sex of the posterior ilium from the Robert J. Terry and William M.
      Bass collections.
AB  - Morphological traits of the posterior ilium are commonly used for sex
      determination in bioarcheological and forensic skeletal analysis. This study was
      designed to compare the classification correctness of standard scoring systems
      and measurements of the posterior ilium, including using logistic regression, to
      develop new formulae to predict sex. Metric measurements and morphological scores
      for the preauricular sulcus (PS), the elevation of the auricular surface, and the
      greater sciatic notch width were recorded for 97 males and 101 females of both
      European and African ancestry from the William M. Bass and Terry Collections.
      Correct classification of sex was high using individual traits such as the
      greater sciatic notch score (88.4%), the presence or absence of a PS (78.8%), and
      the scoring of a present PS as 1, 2, or 3 (100%). Furthermore, an equation
      combining multiple traits of the posterior ilium had a high classification of
      94.9%.

PMID- 22458802
TI  - History of malaria research and its contribution to the malaria control success
      in Suriname: a review.
AB  - Suriname has cleared malaria from its capital city and coastal areas mainly
      through the successful use of chloroquine and DDT (dichloro-diphenyl
      trichloroethane) during the Global Malaria Eradication programme that started in
      1955. Nonetheless, malaria transmission rates remained high in the interior of
      the country for a long time. An impressive decline in malaria cases was achieved
      in the past few years, from 14,403 registered cases in 2003 to 1,371 in 2009. The
      introduction of artemisinin-based combination therapy (ACT) in 2004 has further
      fuelled the decrease in the number of infections with Plasmodium falciparum. The
      only population group still heavily burdened with malaria is gold mining industry
      workers. Interestingly, an important part of malaria cases diagnosed and treated
      in Suriname originate from border regions. Therefore, practical initiatives of
      combined efforts between neighbouring countries must be scaled up in order to
      effectively attack these specific areas. Furthermore, it is of vital importance
      to keep investing into the malaria control programme and public awareness
      campaigns. Especially the correct use of ACT must be promoted in order to prevent
      the emergence of resistance. However, effective preventive measures and adequate
      therapeutic options are on their own not enough to control, let alone eliminate
      malaria. Changing personal and social behaviour of people is particularly
      difficult, but crucial in making the current success sustainable. With this in
      mind, research on successfully implemented interventions, focusing on behavioural
      modifications and methods of measuring their effectiveness, must be expanded.

PMID- 22458804
TI  - Periodontitis and Alzheimer's disease: oral systemic link still on the rise?
AB  - Over the past few years, there has been a rapid rise in the older segments of the
      world population, which has brought along with it a major health concern:
      dementia. Alzheimer's disease, considered to be the most common cause of
      dementia, has become a prospect feared by the elderly. Inflammation of the brain
      is strongly implicated in Alzheimer's disease which could be enhanced by systemic
      inflammation. Periodontitis being a chronic inflammatory condition, which can
      cause systemic inflammation, the question is whether chronic periodontitis can
      initiate or hasten the rate of progression of Alzheimer's disease in susceptible
      individuals. In this article, the authors outline the proposed oral systemic link
      between periodontitis and Alzheimer's disease.

PMID- 22458805
TI  - Creatine treatment to relieve muscle pain caused by thyroxine replacement
      therapy.

PMID- 22458806
TI  - "I will never forget": what we learned from medical student reflections on a
      palliative care experience.
AB  - PURPOSE: To use reflective writing to evaluate a new required palliative care
      experience for third year medical students. METHOD: The authors used a constant
      comparison method based on grounded theory to conduct a thematic analysis of
      reflective writings produced by third-year medical students completing a
      mandatory week-long clinical rotation in palliative care during academic year
      2010 at the University of Louisville. RESULTS: Two broad thematic categories were
      identified: what the students learned and what the students experienced. Student
      writings revealed learning about palliative care (pain management, family
      meetings, goals of care, patient-family centered care, timing of palliative care,
      and delivering bad news); being a doctor (knowledge, communication, presence,
      empathy, not giving false hope, and person-focused care); the patient (importance
      of family, the experience of dying, and the uniqueness of each patient); and
      themselves (need to be non-judgmental, ability to do palliative care, self
      limitations, becoming a better physician, and dealing with death). Student
      reflections centered on encounters with patients and families, internal emotional
      responses, and self-transformation. CONCLUSIONS: Systematic analysis of
      reflective writing provides educators with valuable data about students' learning
      experiences. These results may inform the design and modification of the
      curriculum.

PMID- 22458808
TI  - Distinctive microRNAs in esophageal tumor: early diagnosis, prognosis judgment,
      and tumor treatment.
AB  - Esophageal tumor (ET) is aggressive and has poor prognosis. Although the
      incidence of ET has been reduced by the changing tumor profile, the 5-year
      survival and mortality rate of ET has not significantly changed, and the outlook
      has remained bleak. Therefore, new molecular markers for early diagnosis and
      prognosis judgment are urgently required. In recent years, tumor has been widely
      regarded as genetic disease along with epigenetic abnormalities. DNA methylation,
      histone deacetylation, chromatin remodeling, gene imprinting, and noncoding RNA
      regulation are the major parts of epigenetic regulation. Mounting evidence exists
      that miRNAs (microRNA), a class of small, endogenous, and non-protein-coding
      RNAs, provide a novel tool for early clinical diagnosis, prognosis judgment, and
      gene therapy of ET. In this review, we provide a general overview of the
      connection between miRNA profiles and their target genes. We also describe in
      detail in ET from the aspect of clinical insights, the potential application of
      miRNAs as biomarkers, potential diagnostic and therapeutic tools.

PMID- 22458807
TI  - Regulated interaction of protein phosphatase 1 and protein phosphatase 2A with
      phospholipase C-related but catalytically inactive protein.
AB  - Protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) are major members
      of the protein serine/threonine phosphatase families. We have identified PP1 and
      PP2A as interacting partners of PRIP (phospholipase C-related but catalytically
      inactive protein), a protein isolated in our laboratory. We first investigated
      the interaction of PRIP with two phosphatases, using purified recombinant
      proteins. PRIP immobilized on beads pulled down the catalytic subunits of both
      PP1 and PP2A, indicating that the interactions were in a direct manner, and the
      binding of PP1 and the binding of PP2A to PRIP were mutually exclusive. Site
      directed mutagenesis experiments revealed that the binding sites for PP1 and PP2A
      on PRIP were not identical, but similar. Phosphorylation of PRIP by protein
      kinase A (PKA) resulted in the weakened binding of PP1, but not PP2A. Rather, the
      dissociation of PP1 from PRIP by phosphorylation accompanied the strengthened
      binding of PP2A in in vitro experiments. This regulation of binding of PP1 and
      PP2A to PRIP by PKA-dependent phosphorylation was also observed in living cells
      treated with forskolin or isoproterenol. These results suggested that PRIP
      directly interacts with the catalytic subunits of two distinct phosphatases in a
      mutually exclusive manner and the interactions are regulated by phosphorylation,
      thus functioning as a scaffold to regulate the activities and subcellular
      localizations of both PP1 and PP2A in phospho-dependent cellular signaling.

PMID- 22458809
TI  - Regulating naive and memory CD8 T cell homeostasis--a role for protein tyrosine
      phosphatases.
AB  - A complex network of signalling events coordinate the differentiation, activation
      and maintenance of T lymphocytes. Tyrosine phosphorylation and dephosphorylation
      by protein tyrosine kinases and protein tyrosine phosphatases (PTPs)
      respectively, are critical for the activation and propagation of these signalling
      cascades. Intriguingly, the removal of tyrosyl phosphate moieties from
      phosphorylated proteins by phosphatases can contribute to both the positive and
      negative regulation of signalling events. The complex and diverse roles of
      individual PTP family members in immune cells is evident by the range of immune
      disorders caused by PTP deficiencies. Central to several such immune disorders is
      the disturbance of T cell homeostasis, as characterized by aberrant cell growth,
      survival and activation. The survival and homeostatic proliferation of naive and
      memory CD8 T cells is primarily regulated by signalling events downstream of the
      T cell receptor complex and common gamma chain cytokine receptors, events
      frequently targeted by PTP activity. We review the primary PTPs involved in CD8 T
      cell homeostasis, focusing on the signalling nodes that they target. In addition,
      because the mechanisms that co-ordinate PTP activity are only partially
      understood, we discuss currently proposed models of regulation and highlight
      unanswered questions.

PMID- 22458811
TI  - Staying in nursing: what factors determine whether nurses intend to remain
      employed?
AB  - AIM: To test a model of eight thematic determinants of whether nurses intend to
      remain in nursing roles. BACKGROUND: Despite the dramatic increase in the supply
      of nurses in England over the past decade, a combination of the economic
      downturn, funding constraints and more generally an ageing nursing population
      means that healthcare organizations are likely to encounter long-term problems in
      the recruitment and retention of nursing staff. DESIGN: Survey. METHOD: Data were
      collected from a large staff survey conducted in the National Health Service in
      England between September-December 2009. A multi-level model was tested using
      MPlus statistical software on a sub-sample of 16,707 nurses drawn from 167
      healthcare organizations. RESULTS: Findings were generally supportive of the
      proposed model. Nurses who reported being psychologically engaged with their jobs
      reported a lower intention to leave their current job. The perceived availability
      of developmental opportunities, being able to achieve a good work-life balance
      and whether nurses' encountered work pressures were also influencing factors on
      their turnover intentions. However, relationships formed with colleagues and
      patients displayed comparatively small relationships with turnover intentions.
      CONCLUSION: The focus at the local level needs to be on promoting employee
      engagement by equipping staff with the resources (physical and monetary) and
      control to enable them to perform their tasks to standards they aspire to and
      creating a work environment where staff are fully involved in the wider running
      of their organizations, communicating to staff that patient care is important and
      the top priority of the organization.

PMID- 22458810
TI  - Molecular characterization of the Lotus japonicus NRT1(PTR) and NRT2 families.
AB  - Nitrate is an essential element for plant growth, both as a primary nutrient in
      the nitrogen assimilation pathway and as an important signal for plant
      development. Low- and high-affinity transport systems are involved in the nitrate
      uptake from the soil and its distribution between different plant tissues. By an
      in silico search, we identified putative members of both systems in the model
      legume Lotus japonicus. We investigated, by a time course analysis, the
      transcripts abundance in root tissues of nine and four genes encoding putative
      low-affinity (NRT1) and high-affinity (NRT2) nitrate transporters, respectively.
      The genes were sub-classified as inducible, repressible and constitutive on the
      basis of their responses to provision of nitrate, auxin or cytokinin.
      Furthermore, the analysis of the pattern of expression in root and nodule tissues
      after Mesorhizobium loti inoculation permitted the identification of sequences
      significantly regulated during the symbiotic interaction. The interpretation of
      the global regulative networks obtained allowed to postulate roles for nitrate
      transporters as possible actors in the cross-talks between different signalling
      pathways triggered by biotic and abiotic factors.

PMID- 22458812
TI  - HLA alleles in Brazilian patients with fissured tongue.
AB  - BACKGROUND: Fissured tongue (FT) is a clinical condition manifested by numerous
      little furrows on the tongue's surface. Previously, the authors observed an
      association with HLA-C*06 in psoriasis (PS) and benign migratory glossitis (BMG);
      however, HLA-C was not surveyed in FT. OBJECTIVE: This study investigated the
      association between HLA alleles and FT. METHODS: Thirty-three FT bearers were
      studied, after evaluation of criteria for inclusion. These patients did not
      present PS, BMG or any other conditions associated with FT. The control group
      (CG) was composed of 561 individuals with HLA-A, 560 individuals with HLA-B, 168
      individuals with HLA-C, 564 individuals with HLA-DRB1 and 390 individuals with
      HLA-DQB1. Samples from these individuals were processed to extract DNA. The HLA
      classes I and II were determined using the reverse line blot technique. The
      frequencies of HLA antigens found in patients were compared with the CG using
      Fisher's exact test. RESULTS: The comparison of the frequencies of HLA antigens
      found in the patient groups and in CG revealed no association with any of the
      alleles studied, except for HLA-A*01, which exhibited a decreased frequency in
      patient groups. HLA-C*06 was detected in 7.57% of FT patients and 10.42% of the
      CG (not significant). CONCLUSION: The lack of association of FT with HLA-C*06
      reinforces the proposal that this disease does not have a common genetic factor
      in the triad of BMG, FT and PS.

PMID- 22458813
TI  - Functional group-selective adsorption using scanning tunneling microscopy.
AB  - In this study, we selectively enhanced two types of adsorption of 3
      mercaptoisobutyric acid on a Ge(100) surface by using the tunneling electrons
      from an STM and the catalytic effect of an STM tip. 3-Mercaptoisobutyric acid has
      two functional groups: a carboxylic acid group at one end of the molecule and a
      thiol group at the other end. It was found that the adsorption occurring through
      the carboxylic acid group was selectively enhanced by the application of
      electrons tunneling between an STM tip and the surface. Using this enhancement,
      it was possible to make thiol group-terminated surfaces at any desired location.
      In addition, via the use of a tungsten STM tip coated with a tungsten oxide
      (WO(3)) layer, we selectively catalyzed the adsorption through the thiol group.
      Using this catalysis, it was possible to generate carboxylic acid group
      terminated surfaces at any desired location. This functional group-selective
      adsorption using STM could be applied in positive lithographic methods to produce
      semiconductor substrates terminated by desired functional groups.

PMID- 22458814
TI  - Trends in domestic animal medico-legal pathology cases submitted to a veterinary
      diagnostic laboratory 1998-2010.
AB  - Pathologists at veterinary diagnostic laboratories receive medico-legal cases
      from a variety of animal species for postmortem examination. A search of
      computerized records of the Animal Health Laboratory, University of Guelph,
      Guelph, Ontario, Canada from 1998 to 2010 identified 1706 medicolegal cases.
      These were categorized according to the history as criminal investigations,
      anesthetic-related deaths, insurance, litigation, malpractice cases, and
      regulatory cases. Statistically significant linear trends in the proportion of
      medicolegal cases for all animals and criminal cases for companion animals were
      identified over the 12 year period. Companion animals had significantly greater
      odds of being a medicolegal case in all categories except for insurance and
      regulatory cases, compared to noncompanion animals. Based on pathology reports
      for the 271 criminal cases, 43.1% were consistent with neglect, 29.2% were
      compatible with non-accidental injury, 4.80% were poisonings, 10.7% were deemed
      to be due to natural disease, and 11.43% were inconclusive.

PMID- 22458815
TI  - First trimester Down syndrome screening is less effective and the number of
      invasive procedures is increased in women younger than 35 years of age.
AB  - OBJECTIVES: We evaluated the performance of first trimester screening for Down
      syndrome in women less than 35 years of age (study group) and in women aged 35
      years or more (control group) in an unselected low-risk population. METHODS: The
      study group comprised a total of 63,945 women who participated in the first
      trimester combined screening in public health care in Finland during the study
      period of 1 May 2002 to 31 December 2008. Women at the age of 35 or more (n =
      13,004) were controls. Prevalence of Down syndrome, detection rate, false
      positive rate and number of invasive procedures needed to detect a single case of
      Down syndrome were analyzed in both groups. RESULTS: The overall prevalence of
      Down syndrome (n = 73) in the study group was 1:876. The number of detected cases
      was 54. The detection rate was 74.0% with a false positive rate of 2.8%. Number
      of invasive procedures needed to detect a single case of Down syndrome was 33. In
      the control group, the detection rate was 87.0% with a false positive rate of
      11.9%. The number of invasive procedures needed to detect a single case of Down
      syndrome was 15. The differences in detection rate and false positive rate were
      significant, P < 0.012, P < 0.001, respectively. CONCLUSION: The overall
      detection rate given for the entire population is an overestimate for a woman
      younger than the age of 35, which should be taken into consideration when
      counselling women of that age.

PMID- 22458817
TI  - Comparative modular analysis of gene expression in vertebrate organs.
AB  - BACKGROUND: The degree of conservation of gene expression between homologous
      organs largely remains an open question. Several recent studies reported some
      evidence in favor of such conservation. Most studies compute organs' similarity
      across all orthologous genes, whereas the expression level of many genes are not
      informative about organ specificity. RESULTS: Here, we use a modularization
      algorithm to overcome this limitation through the identification of inter-species
      co-modules of organs and genes. We identify such co-modules using mouse and human
      microarray expression data. They are functionally coherent both in terms of genes
      and of organs from both organisms. We show that a large proportion of genes
      belonging to the same co-module are orthologous between mouse and human.
      Moreover, their zebrafish orthologs also tend to be expressed in the
      corresponding homologous organs. Notable exceptions to the general pattern of
      conservation are the testis and the olfactory bulb. Interestingly, some co
      modules consist of single organs, while others combine several functionally
      related organs. For instance, amygdala, cerebral cortex, hypothalamus and spinal
      cord form a clearly discernible unit of expression, both in mouse and human.
      CONCLUSIONS: Our study provides a new framework for comparative analysis which
      will be applicable also to other sets of large-scale phenotypic data collected
      across different species.

PMID- 22458818
TI  - Homocysteine and hydroxyproline levels in patients with primary open-angle
      glaucoma.
AB  - AIM: To assess the levels of homocysteine (Hcy) and hydroxyproline (Hyp) in
      aqueous humor and plasma of human eyes with primary open-angle glaucoma (POAG)
      and to correlate their concentrations with the severity of glaucoma. METHODS:
      Fifty patients with POAG and 35 patients with senile cataract (control group)
      were enrolled in the study prospectively. Aqueous humor samples were obtained by
      paracentesis from glaucoma and cataract patients who were undergoing elective
      surgery. Aqueous humor and corresponding plasma samples were analyzed for Hcy and
      Hyp concentrations by high-performance liquid chromatography and spectrometry,
      respectively. RESULTS: Hcy and Hyp levels were significantly higher in aqueous
      humor of POAG patients with respect to the comparative group of cataract patients
      (p < 0.001). No significant difference in the levels of Hcy and Hyp in plasma of
      POAG and cataract patients. A positive correlation was found between Hcy and Hyp
      in aqueous humor of POAG patients (p < 0.001). No significant correlation was
      found between either Hcy or Hyp levels and the severity of visual field loss.
      CONCLUSION: Increased levels of aqueous humor Hcy and Hyp may be associated with
      POAG. In addition, Hcy and Hyp may be useful protein levels in aqueous humor of
      POAG patients as a consequence of glaucomatous damage.

PMID- 22458819
TI  - The spasm-pain-spasm cycle.

PMID- 22458821
TI  - The effect of different training programs on antioxidant status, oxidative
      stress, and metabolic control in type 2 diabetes.
AB  - We compared the effects of 12 weeks of 3 different exercise types on type 2
      diabetic (T2DM) male and female human subjects, randomly divided into 4 groups:
      aerobic training (AT; n = 11), strength training (ST; n = 10), combined training
      (CBT; n = 10), and no training (NT; n = 12). Metabolic control, anthropometric
      parameters, lipid and hematological profiles, kidney and liver function markers,
      hormones, antioxidant enzymes, and oxidative stress markers were assessed prior
      to and after the training programs. At baseline, fasting blood glucose and
      hemoglobin A(1c) in the ST group were higher than in the NT group; after the
      training, we no longer observed differences in these groups, suggesting an
      improvement on these parameters. In the AT group, catalase and superoxide
      dismutase activity, nitrite concentration, levels of sulfhydryl groups, and peak
      rate of oxygen consumption were elevated after the training (p < 0.05). No
      changes were observed in antioxidant enzymes or oxidative stress markers in the
      ST group. The levels of sulfhydryl groups diminished in the NT group (p < 0.01)
      and increased in the CBT group (p < 0.05). These data demonstrate that the AT
      program for the T2DM subjects provided important upregulation in antioxidant
      enzymes and increased nitric oxide bioavailability, which may help minimize
      oxidative stress and the development of the chronic complications of diabetes. We
      propose that the beneficial effects observed in the metabolic parameters of the
      ST group occurred in response to the poor baseline metabolic health n this group,
      and not necessarily in response to the training itself.

PMID- 22458822
TI  - Photodegradation mechanisms of 1-nitropyrene, an environmental pollutant: the
      effect of organic solvents, water, oxygen, phenols, and polycyclic aromatics on
      the destruction and product yields.
AB  - This work describes studies of the photodegradation mechanism of 1-nitropyrene (1
      NO(2)Py) in a chemical model system consisting of an organic solvent and known
      constituents of an aerosol particle. Photoproducts such as 1-hydroxypyrene (1
      OHPy), 1-hydroxy-x-nitropyrenes (1-OH-x-NO(2)Py), 1-nitrosopyrene, and 1,6- and
      1,8-pyrenediones were identified by high-performance liquid chromatography (HPLC)
      and HPLC/mass spectrometry (HPLC/MS) techniques, and their quantum yields show a
      significant dependence on the type of solvent. The photodegradation quantum yield
      of 1-NO(2)Py, phi((-1-NO2Py)), was larger in toluene, benzene, and polar protic
      solvents (10(-3)) in comparison with nonpolar and polar aprotic solvents, where
      the yield is on the order of 10(-4). In solvents with an abstractable hydrogen
      atom, the products formed in higher yields were 1-OHPy and 1-OH-x-NO(2)Py. These
      represent 60-80% of the photodestruction yield and result from abstraction and
      recombination reactions of the pyrenoxy radical, an intermediate postulated to be
      formed as a result of a nitro-nitrite rearrangement in nitroaromatics. The small
      O(2) effect in the photodegradation yield and the quenching experiments with
      azulene demonstrate the small contribution of the (3)(pi,pi*) state in the 1
      NO(2)Py photoreaction. The nitrosopyrene product was not observed under these
      conditions, demonstrating the participation of the (3)(pi,pi*) state in its
      formation. In the presence various phenol aerosol constituents, the
      photodegradation yield increased by 10-fold in all solvents. This effect is
      partly ascribed to the reaction of the (3)(pi,pi*) state with the phenol. The
      effect of water resulted in the reduction of the 1-NO(2)Py photodegradation yield
      and of its photoproducts. The phototodegradation of 1-NO(2)Py was also studied in
      a viscous solvent, hexadecane, and it was determined that this medium does not
      inhibit its photodecay.

PMID- 22458823
TI  - Impact of trash burning on air quality in Mexico City.
AB  - Air pollution experienced by expanding urban areas is responsible for serious
      health effects and death for millions of people every year. Trash burning is a
      common disposal method in poor areas, yet it is uncontrolled in many countries,
      and its contribution to air pollution is unclear due to uncertainties in its
      emissions. Here we develop a new trash burning emission inventory for Mexico City
      based on inverse socioeconomic levels and recently measured emission factors, and
      apply a chemistry-transport model to analyze the effects on pollutant
      concentrations. Trash burning is estimated to emit 25 tons of primary organic
      aerosols (POA) per day, which is comparable to fossil fuel POA emissions in
      Mexico City, and causes an increase in average organic aerosol concentrations of
      ~0.3 MUg m(-3) downtown and up to 2 MUg m(-3) in highly populated suburbs near
      the sources of emission. An evaluation using submicrometer antimony suggests that
      our emission estimates are reasonable. Mitigation of trash burning could reduce
      the levels of organic aerosols by 2-40% and those of PM(2.5) by 1-15% over the
      metropolitan area. The trash burning contributions to carbon monoxide, nitrogen
      oxides, and volatile organic compounds were found to be very small (<3%), and
      consequently the contributions to secondary nitrate, sulfate, and secondary
      organic aerosols are also very small.

PMID- 22458824
TI  - Robotic-based carbon ion therapy and patient positioning in 6 degrees of freedom:
      setup accuracy of two standard immobilization devices used in carbon ion therapy
      and IMRT.
AB  - PURPOSE: To investigate repositioning accuracy in particle radiotherapy in 6
      degrees of freedom (DOF) and intensity-modulated radiotherapy (IMRT, 3 DOF) for
      two immobilization devices (Scotchcast masks vs thermoplastic head masks)
      currently in use at our institution for fractionated radiation therapy in head
      and neck cancer patients. METHODS AND MATERIALS: Position verifications in
      patients treated with carbon ion therapy and IMRT for head and neck malignancies
      were evaluated. Most patients received combined treatment regimen (IMRT plus
      carbon ion boost), immobilization was achieved with either Scotchcast or
      thermoplastic head masks. Position corrections in robotic-based carbon ion
      therapy allowing 6 DOF were compared to IMRT allowing corrections in 3 DOF for
      two standard immobilization devices. In total, 838 set-up controls of 38 patients
      were analyzed. RESULTS: Robotic-based position correction including correction of
      rotations was well tolerated and without discomfort. Standard deviations of
      translational components were between 0.5 and 0.8 mm for Scotchcast and 0.7 and
      1.3 mm for thermoplastic masks in 6 DOF and 1.2-1.4 mm and 1.0-1.1 mm in 3 DOF
      respectively. Mean overall displacement vectors were between 2.1 mm (Scotchcast)
      and 2.9 mm (thermoplastic masks) in 6 DOF and 3.9-3.0 mm in 3 DOF respectively.
      Displacement vectors were lower when correction in 6 DOF was allowed as opposed
      to 3 DOF only, which was maintained at the traditional action level of >3 mm for
      position correction in the pre-on-board imaging era. CONCLUSION: Setup accuracy
      for both systems was within the expected range. Smaller shifts were required when
      6 DOF were available for correction as opposed to 3 DOF. Where highest possible
      positioning accuracy is required, frequent image guidance is mandatory to achieve
      best possible plan delivery and maintenance of sharp gradients and optimal normal
      tissue sparing inherent in carbon ion therapy.

PMID- 22458825
TI  - Comparison of plantar loads during running on different overground surfaces.
AB  - The objective of this study is to compare plantar loads during running on
      different overground surfaces. Fifteen heel-to-toe runners participated in the
      study. Plantar load data were collected and analyzed using an insole sensor
      system during running on concrete, synthetic rubber, and grass surfaces at a
      running speed of 3.8 m/s. Compared with running on concrete surface, running on
      natural grass showed a lower magnitude of maximum plantar pressure at the total
      foot (451.8 kPa vs. 401.7 kPa, p = 0.016), lateral midfoot (175.3 kPa vs. 148.0
      kPa, p = 0.004), central forefoot (366.3 kPa vs. 336.8 kPa, p = 0.003), and
      lateral forefoot (290.2 kPa vs. 257.9 kPa, p = 0.004). Moreover, running on
      natural grass showed a longer relative contact time compared with running on a
      concrete surface at the central forefoot (81.9% vs. 78.8%, p = 0.017) and lateral
      forefoot (75.2% vs. 73.1%, p = 0.007). No significant difference was observed in
      other multiple comparisons. Different surfaces affected the plantar loads while
      running. The differences may help us to understand potential injury mechanisms.

PMID- 22458826
TI  - Nature of tackles that result in injury in professional rugby league.
AB  - A total of 31,655 tackles in 48 professional rugby league matches were coded from
      video for height and direction of tackle on the ball carrier. Injuries were
      recorded by team medical staff for injury date, time, site, type, mechanism,
      severity, and player position. Tackle-related injuries were most frequently the
      result of two tacklers being involved in tackling the ball carrier from the side
      at shoulder or midtorso body levels. The ball carrier had a higher injury rate
      when tackled from behind his visual field at shoulder height and in the fourth
      quarter of matches. Tacklers had a higher risk of injury when tackling from the
      side of the ball carrier, as the first tackler, and in the third quarter of
      matches. Coaches should focus on practicing correct technique during tackling
      with two or more tacklers and when tackling in the ball carrier's blind vision
      area.

PMID- 22458827
TI  - The prevalence of patellofemoral joint disorders with surgical endpoint.
AB  - The frequency of exercise-related injuries for physical activities and sports
      that have specifically lead to surgical intervention are rarely reported,
      especially regarding the patellofemoral articulation. Medical records from 1992
      to 2005 of a multisite, urban-based hospital serving both large urban and rural
      populations were analyzed retrospectively. Injury data were presented by age,
      gender, and sport of choice. Significant (chi2 = (6,519) = 31.097, p < .001)
      differences were found between age categories (adolescent, teenage, and adult)
      for the injuries leading to surgery. Significant gender (chi2 (3,519) = 18.064, p
      < .001) differences were also found. This study presented a 13-year retrospective
      analysis of injuries to the patellofemoral joint leading to surgical endpoint,
      and found age and gender to significantly influence the frequency of injuries.
      Studies suggest that gender differences have not declined in response to the
      increasing number and experience of female athletes.

PMID- 22458828
TI  - Suitability of verification testing to confirm attainment of VO2max in middle
      aged and older adults.
AB  - The aim of the present study was to test the utility of the verification testing
      procedure in confirming "true" VO2max in older adults completing maximal cycle
      ergometry. Eighteen physically active men and women (age = 59.7 +/- 6.3 yr, ht =
      173.0 +/- 8.8 cm, body mass = 83.2 +/- 16.4 kg, VO2max = 27.7 +/- 5.0 mL/kg/min)
      completed incremental exercise, and returned 1 h after incremental exercise to
      complete a verification phase of constant load exercise at 105% peak work rate.
      During exercise, gas exchange data and heart rate (HR) were continuously
      monitored. VO2max was similar (p > 0.05) between incremental and verification
      bouts (2329 +/- 762 mL/min vs. 2309 +/- 760 mL/min). Findings support use of the
      verification procedure to confirm VO2max attainment in active, middle-aged and
      older adults completing incremental cycle ergometry. This is particularly
      relevant to interpretation of studies that have used repeated measurements of
      VO2max to establish a training effect or when VO2max is used for designing
      exercise prescriptions.

PMID- 22458829
TI  - Exercise duration and blood lactate concentrations following high intensity cycle
      ergometry.
AB  - The aim of this study was to investigate differences in blood lactate
      accumulation following 10 and 20 sec of maximal cycle ergometer exercise. Body
      mass, stature, and age of the group was determined prior to testing (82.57 +/-
      5.94 kg 177 +/- 5.94 cm and 21.42 +/- 1.61 yrs, respectively). Eight male rugby
      union players performed two maximal sprints in a random fashion of 10 and 20 sec
      duration on a cycle ergometer. During the 10 and 20 sec trial, blood lactate
      levels measured were as follows 1.58 +/- 0.78, 4.43 +/- 1.4, and 3.5 +/- 1.2
      mmol.l-1 vs. 1.72 +/- 0.65, 6.14 +/- 2, and 5.68 +/- 2.22 mmol.l-1, respectively.
      Differences were found (P < 0.01) from rest to 5 and 10 min postexercise in both
      groups. Differences in concentration also were found between groups at both
      postexercise stages (P < 0.01). The reduction in blood lactate concentrations
      observed between the 5 to 10 min recovery stages were 0.91 +/- 0.58 mmol.l-1 vs.
      0.46 +/- 0.48 mmol.l-1 following 10 and 20 sec of maximal exercise, respectively
      (P > 0.05). The concentrations observed are interesting and may influence
      recovery time and subsequent exercise performance.

PMID- 22458830
TI  - The effect of the hyperbaric environment on heat shock protein 72 expression in
      vivo.
AB  - Heat shock protein 72 (HSP72) is expressed in response to stress and has been
      demonstrated to follow a diurnal expression pattern within monocytes and is
      sensitive to changes in core temperature. Numerous studies have shown changes in
      HSP72 expression within cell lines exposed to hyperbaric conditions. No studies
      have investigated changes in HSP72 expression in vivo. Six males participated in
      the study and were exposed to hyperbaric air and hyperbaric oxygen a week apart.
      Monocyte HSP72 was analyzed by flow cytometry at 09:00, 13:00, 17:00, 21:00 with
      hyperbaric oxygen or hyperbaric air breathing commencing at 15:00 for 78 min at a
      pressure of 2.8 ATA. HSP72 under normoxia followed the established trend;
      however, following the hyperbaric air or oxygen exposure a reduction in
      detectable HSP72 was observed at 17:00 and 21:00. No changes in core temperature
      were observed between 13:00 and 21:00 for any condition. The data show that HSP72
      expression is impaired following hyperbaric air (HA) exposure, when compared with
      control or hyperbaric oxygen (HO) exposure.

PMID- 22458831
TI  - Fathers' emotional involvement with the neonate: impact of the umbilical cord
      cutting experience.
AB  - AIMS: This paper is a report on a study analysing the effect of the umbilical
      cord cutting experience on fathers' emotional involvement with their infants.
      BACKGROUND: Participation in childbirth offers an opportunity for father and
      mother to share the childbirth experience, so it is vital that midwives improve
      the fathers' participation in this event. DESIGN: A quasi-experimental study with
      a quantitative methodology was implemented. METHODS: One hundred and five fathers
      were recruited as part of a convenience sample in a Maternity Public Hospital in
      a Metropolitan City in Portugal, between January and May of 2008. The Bonding
      Scale, the Portuguese version of the 'Mother-to-Infant Bonding Scale' was used to
      evaluate the fathers' emotional involvement with the neonate at different
      moments: before childbirth, first day after childbirth and first month after
      childbirth. After childbirth, the fathers were divided into three separate groups
      depending on their umbilical cord cutting experience. RESULTS: The results
      demonstrate that the emotional involvement between father and child tends to
      increase during the first days after childbirth and to decrease when evaluated 1
      month after birth, for fathers who did not cut the umbilical cord. However,
      fathers who cut the umbilical cord demonstrate an improvement in emotional
      involvement 1 month later. CONCLUSION: Results suggest that the umbilical cord
      cutting experience benefits the father's emotional involvement with the neonate,
      supporting the benefits of his participation and empowerment in childbirth.

PMID- 22458832
TI  - Long-term outcomes and survival of patients undergoing laparoscopy-assisted
      distal gastrectomy for gastric cancer.
AB  - BACKGROUND AND AIM: Laparoscopic-assisted distal gastrectomy (LADG) has recently
      become an alternative treatment option for gastric cancer. Although LADG is safe
      and feasible in terms of short-term patient results and oncological outcomes, the
      long-term oncological efficacy of LADG has yet to be demonstrated. To that end,
      the long-term results and the survival of patients who underwent LADG are
      described in this study. We also evaluated the oncological safety of using this
      approach for the treatment of gastric cancer. SUBJECTS AND METHODS: Between
      January 2006 and December 2009, 133 patients with lower-third gastric cancer
      underwent LADG performed by a single surgeon. The clinicopathologic
      characteristics, long-term survival, and relapse-free survival were estimated
      using the Kaplan-Meier method. RESULTS: Postoperative morbidity occurred in 5.6%
      of the patients. One patient died within 30 days of undergoing the operation
      (0.8%). The median overall survival (OS) of patients who underwent LADG was 45.0
      months (range, 1.0-69.0 months). The median follow-up period of all patients was
      37.0 months (range, 1.0-69.0 months). The 3-year OS rates according to cancer
      stage were 94.8% at Stage I, 84.6% at stage II, and 50.0% at Stage III. The
      median OS in patients who had a recurrence and those who had not had a recurrence
      was 27.0 (6.0-62.0) and 45.0 (1.0-69.0) months, respectively. CONCLUSIONS: LADG
      with lymph node dissection for gastric cancer is a valuable procedure from
      technical and oncological perspectives with acceptable long-term outcomes.
      Therefore, LADG can be substituted for open distal gastrectomy with similar
      effectiveness.

PMID- 22458833
TI  - Laparoscopic cholecystectomy in a single, non-teaching hospital: an analysis of
      1557 patients.
AB  - BACKGROUND: Laparoscopic cholecystectomy may lead to serious complications,
      although it is the gold standard treatment for gallstones. In this article, the
      aim was to review our experience with laparoscopic cholecystectomies. SUBJECTS
      AND METHODS: All laparoscopic cholecystectomies were performed in a single, non
      teaching hospital between January 2000 and October 2010 and were reviewed
      retrospectively to analyze the effect of preoperative risk factors on outcome and
      the associated major complications. RESULTS: This study included 1557
      laparoscopic cholecystectomies, and the mean age of the patients was 54.1+/-12.3
      years. The mean duration of the operation and the mean length of stay were 43.4
      minutes and 1.2 days, respectively. Conversion to an open cholecystectomy was
      necessary in 39 patients, and thus the conversion rate was 2.5%. In total, 57
      (3.7%) complications occurred in 51 patients. Serious common bile duct injury was
      seen in 4 (0.27%) cases. The other common complications included bile leakage in
      10 (0.64%) and postoperative bleeding in 7 (0.45%) patients. The mortality rate
      was 0.13%. Risk factors for conversion to open surgery were male gender, age >55
      years, emergency admission due to acute cholecystitis, and a history of previous
      acute cholecystitis attacks. Factors that increased the morbidity rate were male
      gender, an American Society of Anesthesiologists score of III, emergency
      admission due to acute cholecystitis, and a history of previous acute
      cholecystitis attacks. CONCLUSIONS: Our results may serve as a baseline for
      comparison with future studies done at single, non-teaching hospitals where
      surgical teams perform laparoscopic cholecystectomies over a long period of time.

PMID- 22458834
TI  - Improvements in laparoscopic treatment for complicated appendicitis.
AB  - BACKGROUND: To determine if results for laparoscopic appendectomy for complicated
      appendicitis have improved with 15 years of experience and advances in
      technology. SUBJECTS AND METHODS: A retrospective review of 169 patients who
      underwent laparoscopic appendectomy in 2009 was performed. Of these, the 25 who
      were identified with gangrenous appendicitis and the 25 with perforated
      appendicitis served as our study population. These patients were compared with 15
      patients with gangrenous appendicitis and 19 patients with perforated
      appendicitis from 1995 who had undergone laparoscopic appendectomy to determine
      if improvements in patient outcome have coincided with improvements in experience
      and technology. Patient demographics, operating time, length of hospitalization,
      and complications were compared and analyzed for statistical significance.
      RESULTS: The two groups were similar regarding age and sex distribution.
      Operating time was unchanged between the two study times. A significant
      improvement was seen in length of stay and a trend toward fewer infectious
      complications in the later study group. CONCLUSION: Experience and advances in
      medical technology have translated into improved results for laparoscopic
      appendectomy for complicated appendicitis.

PMID- 22458835
TI  - Safety and effectiveness of 5-mm and 10-mm electrothermal bipolar vessel sealers
      (LigaSure) in laparoscopic resections for sigmoid colon and rectal cancers.
AB  - BACKGROUND: LigaSureTM (Covidien, Mansfield, MA) has been used in cases
      undergoing laparoscopic colon and rectal resections. This study aims to analyze
      the efficacy and safety of the 5-mm and 10-mm devices. SUBJECTS AND METHODS:
      Patients who received a laparoscopic or hand-assisted laparoscopic operation for
      a tumor located in the sigmoid colon or rectum since 2006 were abstracted from a
      prospectively designed database, and findings were analyzed in two groups based
      on size of the device used during the procedure. The videotapes of the procedures
      were watched, and operation reports were read to obtain further information on
      specific intra- and postoperative complications. Demographics, tumor and
      operation-related information, and postoperative data were compared. RESULTS:
      Among 215 (128 [59.5%] males; median age, 59.5+/-13.8 years) patients, data
      obtained from the 5-mm (n=32) and 10-mm (n=183) groups were identical regarding
      demographics and data related to tumor (localization and stage) and operation
      (number of harvested lymph nodes, conversion rates, operation time,
      intraoperative bleeding, transfusion requirement, reoperation rates,
      complications, 30-day mortality, and length of hospital stay). However, more
      patients underwent an anterior resection in the 10-mm group than in the 5-mm
      group (31.7% versus 15.6%, P<.05). Further analyses found device-related bleeding
      in 8 (3.7%) cases (2 [6.3%] versus 6 [3.3%] in the 5-mm versus 10-mm group,
      respectively, P>.05), requiring further attempts for hemorrhage control (n=6),
      conversion to open surgery (n=1), or relaparotomy (n=1). CONCLUSIONS: The 5-mm
      and 10-mm LigaSure devices are similarly effective and safe during laparoscopic
      sigmoid colon and rectal resections. Severe bleeding from larger vessels may be
      observed, requiring conversion to open surgery or relaparotomy.

PMID- 22458836
TI  - Factors that affect the diagnostic yield of endobronchial ultrasonography
      assisted transbronchial lung biopsy.
AB  - BACKGROUND: Endobronchial ultrasound (EBUS) is a relatively noninvasive procedure
      used to diagnose and stage lung cancer. Although EBUS-guided transbronchial lung
      biopsy (TBLB) procedures for peripheral lesions have higher diagnostic yields
      than traditional TBLB or fluoroscopy-assisted TBLB, the diagnostic yield is not
      100%, and the reasons for this are not clear. SUBJECTS AND METHODS: This
      retrospective study assessed what characteristics influence the diagnostic yield
      of EBUS-guided TBLB. EBUS was used to locate a single peripheral lung nodule or
      mass, and the lesion was biopsied and pathologically characterized. Parameters
      that were evaluated included patient demographics, lesion location, ease of tumor
      sampling, location of the EBUS probe relative to the lesion, pathological volume,
      tumor cell type, and whether physicians were under supervision. RESULTS: Thirty
      nine patients received EBUS-guided TBLB, which correctly identified 76.9% of the
      patients as having lung cancer. For the remaining patients, subsequent surgery
      indicated their tumors were malignant. Univariate logistic regression modeling
      indicated that only the location of the probe relative to the lesion was
      significantly associated with diagnostic yield of EBUS-guided TBLB. When the
      probe was directly within the lesion, it was 8.17 times (odds ratio 8.17; 95%
      confidence interval 1.41, 47.22; P=.019) more likely to have a successful TBLB
      than when the probe was adjacent to the lesion. CONCLUSIONS: In this study, the
      position of the probe relative to a peripheral lung lesion was associated with
      the diagnostic yield of EBUS-guided TBLB. Larger prospective studies are required
      to further assess what influences the diagnostic yield of this technology.

PMID- 22458837
TI  - A prospective audit of safety issues associated with general anesthesia for
      pediatric cardiac magnetic resonance imaging.
AB  - BACKGROUND/OBJECTIVES: Cardiac MRI (CMR) is increasingly used for surgical
      planning and serial monitoring of children with congenital heart disease (CHD).
      For small children, general anesthesia (GA) is required. We describe our
      experience of the safety of GA for pediatric CMR, using data collected
      prospectively over 3 years. METHODS: All consecutive infants undergoing GA for
      CMR at our institution, between November 2005 and May 2008, were included.
      Informed and written consent to participate in research investigation was
      acquired from the guardians of every patient prior to CMR. The cardiac
      anesthetist completed a standardized data collection form during each procedure.
      Information collected included demographics, diagnosis, surgical history,
      anesthetic management, significant incidents, and discharge circumstances.
      RESULTS: A total of 120 patients with varying cardiac physiology and a range of
      hemodynamics underwent GA for CMR during the study period. Gas induction was
      predominantly used, even in those with impaired ventricular function. The
      majority (71%) of procedures were undertaken without significant incident. Minor
      adverse incidents were recorded in 32 patients, mild hypotension being most
      frequent. One major adverse event occurred. A patient with hypoplastic left heart
      syndrome (HLHS) suffered hypotension then cardiac arrest in the scanner. This
      patient was successfully resuscitated. CONCLUSION: Although the majority of cases
      were safe and without incident, the complication rate in children with CHD
      receiving a GA for CMR is higher than in the general pediatric population. This
      reinforces the need for a senior, multidisciplinary team to be involved in the
      care of these children during imaging.

PMID- 22458838
TI  - Highly adaptable two-dimensional metal-organic coordination networks on metal
      surfaces.
AB  - The formation of extended two-dimensional metal-organic coordination networks (2D
      MOCNs) showing high adaptability to surface step edges and structural defects is
      revealed by scanning tunneling microscopy. Rod-like 4,4'-di-(1,4-buta-1,3-diynyl)
      benzoic acid (BDBA) and iron atoms assemble into extended 2D-MOCNs on Au(111) and
      Ag(100) surfaces. Independent from the chosen substrate and its surface symmetry
      the MOCN grows continuously over multiple surface terraces through mutual in
      phase structure adaptation of network domains at step edges as well as on
      terraces. The adaptability of the MOCNs is mainly ascribed to the high degree of
      conformational flexibility of the butadiynyl functionality of the ligand. Despite
      their flexibility, the MOCNs exhibit considerable robustness against annealing at
      high temperatures. The findings show that mesoscale self-assembled functional
      architectures with a high degree of substrate error tolerance can be realized
      with metal coordination networks.

PMID- 22458839
TI  - Time-resolved infrared detection of the proton and protein dynamics during
      photosynthetic oxygen evolution.
AB  - Photosynthetic oxygen evolution by plants and cyanobacteria is performed by water
      oxidation at the Mn(4)CaO(5) cluster in photosystem II. The reaction is known to
      proceed via a light-driven cycle of five intermediates called S(i) states (i = 0
      4). However, the detailed reaction processes during the intermediate transitions
      remain unresolved. In this study, we have directly detected the proton and
      protein dynamics during the oxygen-evolving reactions using time-resolved
      infrared spectroscopy. The time courses of the absorption changes at 1400 and
      2500 cm(-1), which represent the reactions and/or interaction changes of
      carboxylate groups and the changes in proton polarizability of strong hydrogen
      bonds, respectively, were monitored upon flash illumination. The results provided
      experimental evidence that during the S(3) -> S(0) transition, drastic proton
      rearrangement, most likely reflecting the release of a proton from the catalytic
      site, takes place to form a transient state before the oxidation of the
      Mn(4)CaO(5) cluster that leads to O(2) formation. Early proton movement was also
      detected during the S(2) -> S(3) transition. These observations reveal the common
      mechanism in which proton release facilitates the transfer of an electron from
      the Mn(4)CaO(5) cluster in the S(2) and S(3) states that already accumulate
      oxidizing equivalents. In addition, relatively slow rearrangement of carboxylate
      groups was detected in the S(0) -> S(1) transition, which could contribute to the
      stabilization of the S(1) state. This study demonstrates that time-resolved
      infrared detection is a powerful method for elucidating the detailed molecular
      mechanism of photosynthetic oxygen evolution by pursuing the reactions of
      substrate and amino acid residues during the S-state transitions.

PMID- 22458840
TI  - Severe imported malaria in an intensive care unit: a review of 59 cases.
AB  - BACKGROUND: In view of the close relationship of Portugal with African countries,
      particularly former Portuguese colonies, the diagnosis of malaria is not a rare
      thing. When a traveller returns ill from endemic areas, malaria should be the
      number one suspect. World Health Organization treatment guidelines recommend that
      adults with severe malaria should be admitted to an intensive care unit (ICU).
      METHODS: Severe cases of malaria in patients admitted to an ICU were reviewed
      retrospectively (1990-2011) and identification of variables associated with in
      ICU mortality performed. Malaria prediction score (MPS), malaria score for adults
      (MSA), simplified acute physiology score (SAPSII) and a score based on WHO's
      malaria severe criteria were applied. Statistical analysis was performed using
      StataV12. RESULTS: Fifty nine patients were included in the study, all but three
      were adults; 47 (79,6%) were male; parasitaemia on admission, quantified in 48/59
      (81.3%) patients, was equal or greater than 2% in 47 of them (97.9%); the most
      common complications were thrombocytopaenia in 54 (91.5%) patients, associated
      with disseminated intravascular coagulation (DIC) in seven (11.8%), renal failure
      in 31 (52.5%) patients, 18 of which (30.5%) oliguric, shock in 29 (49.1%)
      patients, liver dysfunction in 27 (45.7%) patients, acidaemia in 23 (38.9%)
      patients, cerebral dysfunction in 22 (37.2%) patients, 11 of whom with unrousable
      coma, pulmonary oedema/ARDS in 22 (37.2%) patients, hypoglycaemia in 18 (30.5%)
      patients; 29 (49.1%) patients presented five or more dysfunctions. The case
      fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score
      were the most sensitive to death prediction. In the univariate analysis, death
      was associated with the SAPS II score, cerebral malaria, acute renal and
      respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age,
      partial immunity to malaria, delay in malaria diagnosis and the level of
      parasitaemia were not associated with death in this cohort. CONCLUSION: Severe
      malaria cases should be continued monitored in the ICUs. SAPS II and the WHO
      score are good predictors of mortality in malaria patients, but other specific
      scores deserve to be studied prospectively.

PMID- 22458841
TI  - Incentives as connectors: insights into a breastfeeding incentive intervention in
      a disadvantaged area of North-West England.
AB  - BACKGROUND: Incentive or reward schemes are becoming increasingly popular to
      motivate healthy lifestyle behaviours. In this paper, insights from a qualitative
      and descriptive study to investigate the uptake, impact and meanings of a
      breastfeeding incentive intervention integrated into an existing peer support
      programme (Star Buddies) are reported. The Star Buddies service employs
      breastfeeding peer supporters to support women across the ante-natal, intra
      partum and post-partum period. METHODS: In a disadvantaged area of North West
      England, women initiating breastfeeding were recruited by peer supporters on the
      postnatal ward or soon after hospital discharge to participate in an 8 week
      incentive (gifts and vouchers) and breastfeeding peer supporter intervention. In
      depth interviews were conducted with 26 women participants who engaged with the
      incentive intervention, and a focus group was held with the 4 community peer
      supporters who delivered the intervention. Descriptive analysis of routinely
      collected data for peer supporter contacts and breastfeeding outcomes before and
      after the incentive intervention triangulated and retrospectively provided the
      context for the qualitative thematic analysis. RESULTS: A global theme emerged of
      'incentives as connectors', with two sub-themes of 'facilitating connections' and
      'facilitating relationships and wellbeing'. The incentives were linked to
      discussion themes and gift giving facilitated peer supporter access for proactive
      weekly home visits to support women. Regular face to face contacts enabled
      meaningful relationships and new connections within and between the women,
      families, peer supporters and care providers to be formed and sustained.
      Participants in the incentive scheme received more home visits and total contact
      time with peer supporters compared to women before the incentive intervention.
      Full participation levels and breastfeeding rates at 6-8 weeks were similar for
      women before and after the incentive intervention. CONCLUSION: The findings
      suggest that whilst the provision of incentives might not influence women's
      intentions or motivations to breastfeed, the connections forged provided psycho
      social benefits for both programme users and peer supporters.

PMID- 22458842
TI  - Next-generation small RNA sequencing for microRNAs profiling in Apis mellifera:
      comparison between nurses and foragers.
AB  - MicroRNAs (miRNAs) are endogenous small non-coding RNAs regulating gene
      expression in animals and plants. To find some differentially expressed miRNAs
      that may be associated with age-dependent behavioural changes in honey bees (Apis
      mellifera), we applied next-generation high-throughput sequencing technology to
      detect small RNAs in nurses and foragers. Our results showed that both nurses and
      foragers had a complicated small RNA population, and the length of small RNAs
      varied, 22 nucleotides being the predominant length. Combining deep sequencing
      and bioinformatic analysis, we discovered that nine known miRNAs were
      significantly different between nurses and foragers (P < 0.01; absolute value of
      fold-change >= 1). Some of their target genes were related to neural function.
      Moreover, 67 novel miRNAs were identified in nurses and foragers. Ame-miR-31a and
      ame-miR-13b were further validated using quantitative reverse-transcription PCR
      assays. The present study provides new information on the miRNA abundance of
      honey bees, and enhances our understanding of miRNA function in the regulation of
      honey bee development.

PMID- 22458843
TI  - Angiopoietin-like 4: a decade of research.
AB  - The past decade has seen a rapid development and increasing recognition of
      ANGPTL4 (angiopoietin-like 4) as a remarkably multifaceted protein that is
      involved in many metabolic and non-metabolic conditions. ANGPTL4 has been
      recognised as a central player in various aspects of energy homoeostasis, at
      least in part, via the inhibitory interaction between the coiled-coil domain of
      ANGPTL4 and LPL (lipoprotein lipase). The fibrinogen-like domain of ANGPTL4
      interacts and activates specific integrins to facilitate wound healing, modulates
      vascular permeability, and regulates ROS (reactive oxygen species) level to
      promote tumorigenesis. The present review summarizes these landmark findings
      about ANGPTL4 and highlights several important implications for future clinical
      practice. Importantly, these implications have also raised many questions that
      are in urgent need of further investigations, particularly the transcription
      regulation of ANGPTL4 expression, and the post-translation cleavage and
      modifications of ANGPTL4. The research findings over the past decade have laid
      the foundation for a better mechanistic understanding of the new scientific
      discoveries on the diverse roles of ANGPTL4.

PMID- 22458844
TI  - The leucocyte beta2 (CD18) integrins: the structure, functional regulation and
      signalling properties.
AB  - Leucocytes are highly motile cells. Their ability to migrate into tissues and
      organs is dependent on cell adhesion molecules. The integrins are a family of
      heterodimeric transmembrane cell adhesion molecules that are also signalling
      receptors. They are involved in many biological processes, including the
      development of metazoans, immunity, haemostasis, wound healing and cell survival,
      proliferation and differentiation. The leucocyte-restricted beta2 integrins
      comprise four members, namely alphaLbeta2, alphaMbeta2, alphaXbeta2 and
      alphaDbeta2, which are required for a functional immune system. In this paper,
      the structure, functional regulation and signalling properties of these integrins
      are reviewed.

PMID- 22458845
TI  - False-positive results in ELISA-based anti FVIII antibody assay may occur with
      lupus anticoagulant and phospholipid antibodies.
AB  - The evaluation of a prolonged aPTT often includes Lupus Anticoagulant,
      Antiphospholipid Antibodies, and Factor VIII (FVIII) inhibitors. We have noticed
      that patient samples positive for lupus antibody (LA) are frequently also
      positive for FVIII IgG antibodies in an enzyme-linked immunosorbent assay
      (ELISA), indicating the need for follow-up testing with a more labour-intensive
      functional assay for FVIII inhibition. This study evaluates the potential for a
      FVIII IgG ELISA to yield false-positive results in patient samples positive for
      LA or other antiphospholipid antibodies. A total of 289 residual de-identified
      patient samples positive for LA (n = 143), anti-cardiolipin IgG (n = 84), or
      beta2-glycoprotein antibody (n = 62) were tested for FVIII IgG using a commercial
      ELISA. Samples with positive FVIII IgG ELISA results were further tested for
      FVIII activity using a clot-based FVIII inhibitor assay. The FVIII IgG ELISA
      yielded positive results in 39 (13%) of the samples tested, including 13/143
      (13%) LA-positive, 15/85 (18%) aCL IgG-positive and 6/62 (10%) beta2-glycoprotein
      IgG-positive samples. The clot-based FVIII inhibitor assay yielded negative
      results in all 39 FVIII IgG-positive specimens tested, indicating discrepancy
      with the FVIII IgG ELISA results. Patient specimens positive for LA, aCL IgG, or
      beta2-glycoprotein IgG may yield false-positive results for FVIII antibodies.
      Caution is warranted in interpreting FVIII antibody results in these cases.

PMID- 22458846
TI  - Therapeutic efficiency of everolimus and lapatinib in xenograft model of human
      colorectal carcinoma with KRAS mutation.
AB  - KRAS mutation is a negative predictive prognostic factor during metastatic
      colorectal cancer treatment with antiepidermal growth factor receptor antibodies.
      For affected patients, new therapeutics must be explored. Our objective was to
      study efficacy of two drugs with different mechanisms of action, everolimus (mTOR
      inhibitor) and lapatinib (tyrosine kinase inhibitor), in a mouse xenograft model.
      We chose a model obtained after engraftment of a tumor originating from a human
      tumor collection. The patient was affected by a metastasis colorectal carcinoma
      resistant to cetuximab with KRAS mutation. From a previous study in mice, we know
      that everolimus is a P-glycoprotein (P-gp) substrate and that a lapatinib
      pretreatment increases significantly (2.6-fold) everolimus AUC by inhibiting its
      intestinal P-gp efflux. We hence tested the effect of these drugs alone or
      combined. Mice bearing the xenografts were divided in four groups: control,
      lapatinib, everolimus, and L/E group (L/E: 2 days of lapatinib 200 mg/kg and then
      3 days of everolimus 1 mg/kg). Tumor volumes and treatment toxicities were
      evaluated. Sixteen days after treatment initiation, the group L/E was the first
      one in which tumor volume average was significantly lower than the one of control
      group (193 +/- 90 vs. 395 +/- 171 mm(3) ; P = 0.0025). After 4 weeks of
      treatment, inhibition of tumor growth in lapatinib, everolimus, and L/E groups
      reached, respectively, 49, 53, and 57%. Each drug showed significant antitumor
      activity. Only moderate hematologic toxicity signs were observed. These results
      lead to new perspectives for new oral drugs in metastatic KRAS-mutated colorectal
      cancer resistant to standard chemotherapy. 

PMID- 22458848
TI  - Cells take up and recover from protein-stabilized single-wall carbon nanotubes
      with two distinct rates.
AB  - Single-wall carbon nanotubes (SWCNTs) are increasingly being investigated for use
      in biomedical applications for intracellular imaging and ablation, as well as
      vehicles for drug and gene delivery. One major obstacle to the development of
      safe, controlled, and effective SWCNT-based biomedical materials is limited
      quantification of dosage- and time-dependent uptake kinetics, cellular effects,
      and recovery profiles. Here, we quantified NIH-3T3 cellular uptake of and
      recovery from individualized SWCNTs dispersed using a biocompatible dispersing
      agent, bovine serum albumin (BSA). Uptake and recovery were determined by
      monitoring the mass of SWCNTs-BSA per cell, as a function of SWCNTs-BSA over the
      concentration range of 1 to 100 MUg mL(-1) and time range of seconds to days. To
      determine SWCNTs-BSA biocompatibility as a function of uptake and recovery,
      cytotoxicity, proliferation potential, and cell phenotype were monitored for each
      condition. Interestingly, the rate of cellular uptake of SWCNTs-BSA was rapid,
      reaching steady state within ~1 min, in agreement with modeling. We also observed
      a threshold SWCNT exposure level (>1 MUg mL(-1)) above which internalization is
      saturated and uptake scales linearly with exposure amount. Cells were able to
      recover from SWCNTs-BSA over ~30 h, regardless of dosage level or exposure time.
      We suggest that these differential rates of uptake and recovery, quantified in
      our work, may enable cell-based SWCNT delivery systems.

PMID- 22458847
TI  - The major facilitator superfamily (MFS) revisited.
AB  - The major facilitator superfamily (MFS) is the largest known superfamily of
      secondary carriers found in the biosphere. It is ubiquitously distributed
      throughout virtually all currently recognized organismal phyla. This superfamily
      currently (2012) consists of 74 families, each of which is usually concerned with
      the transport of a certain type of substrate. Many of these families, defined
      phylogenetically, do not include even a single member that is functionally
      characterized. In this article, we probe the evolutionary origins of these
      transporters, providing evidence that they arose from a single 2-transmembrane
      segment (TMS) hairpin structure that triplicated to give a 6-TMS unit that
      duplicated to a 12-TMS protein, the most frequent topological type of these
      permeases. We globally examine MFS protein topologies, focusing on exceptional
      proteins that deviate from the norm. Nine distantly related families appear to
      have members with 14 TMSs in which the extra two are usually centrally localized
      between the two 6-TMS repeat units. They probably have arisen by intragenic
      duplication of an adjacent hairpin. This alternative topology probably arose
      multiple times during MFS evolution. Convincing evidence for MFS permeases with
      fewer than 12 TMSs was not forthcoming, leading to the suggestion that all 12
      TMSs are required for optimal function. Some homologs appear to have 13, 14, 15
      or 16 TMSs, and the probable locations of the extra TMSs were identified. A few
      MFS permeases are fused to other functional domains or are fully duplicated to
      give 24-TMS proteins with dual functions. Finally, the MFS families with no known
      function were subjected to genomic context analyses leading to functional
      predictions.

PMID- 22458849
TI  - HbCIPK2, a novel CBL-interacting protein kinase from halophyte Hordeum
      brevisubulatum, confers salt and osmotic stress tolerance.
AB  - Protein kinases play an important role in regulating the response to abiotic
      stress in plant. CIPKs are plant-specific signal transducers, and some members
      have been identified. However, the precise functions of novel CIPKs still remain
      unknown. Here we report that HbCIPK2 is a positive regulator of salt and osmotic
      stress tolerance. HbCIPK2 was screened out of the differentially expressed
      fragments from halophyte Hordeum brevisubulatum by cDNA-AFLP technique, and was a
      single-copy gene without intron. Expression of HbCIPK2 was increased by salt,
      drought and ABA treatment. HbCIPK2 is mainly localized to the plasma membrane and
      nucleus. Ectopic expression of 35S:HbCIPK2 not only rescued the salt
      hypersensitivity in Arabidopsis mutant sos2-1, but also enhanced salt tolerance
      in Arabidopsis wild type, and exhibited tolerance to osmotic stress during
      germination. The HbCIPK2 contributed to the ability to prevent K(+) loss in root
      and to accumulate less Na(+) in shoot resulting in K(+) /Na(+) homeostasis and
      protection of root cell from death, which is consistent with the gene expression
      profile of HbCIPK2-overexpressing lines. These findings imply possible novel
      HbCIPK2-mediated salt signalling pathways or networks in H. brevisubulatum.

PMID- 22458850
TI  - Multiple peer group self-identification and adolescent tobacco use.
AB  - Associations between peer group self-identification and smoking were examined
      among 2,698 ethnically diverse middle school students in Los Angeles who self
      identified with groups such as Rockers, Skaters, and Gamers. The sample was 47.1%
      male, 54.7% Latino, 25.4% Asian, 10.8% White, 9.1% Other ethnicity, and 59.3%
      children of immigrant parents. Multiple group self-identification was common: 84%
      identified with two or more groups and 65% identified with three or more groups.
      Logistic regression analyses indicated that as students endorsed more high-risk
      groups, the greater their risk of tobacco use. A classification tree analysis
      identified risk groups based on interactions among ethnicity, gender, and group
      self-identification. Psychographic targeting based on group self-identification
      could be useful to design more relevant smoking prevention messages for
      adolescents who identify with high-risk peer groups.

PMID- 22458851
TI  - An overview of renal replacement therapy and health care personnel deficiencies
      in sub-Saharan Africa.
AB  - Chronic kidney disease (CKD) is a public health problem in sub-Saharan Africa
      (SSA) but there is limited data to guide programs or plan interventions. To help
      set priorities and understand the needs for renal replacement therapy a baseline
      assessment is required. World Health Organization (WHO) databases and Medline
      were searched to determine the number of physicians, nephrologists, and dialysis
      centers and patients in SSA. Data on renal transplant (RTx) programs were
      collected from the WHO Global Observatory on Donation & Transplantation database
      for deceased-donor and living-donor RTx. Of the 47 countries in SSA only 15 had
      recent data with most rates of physicians per 10,000 population under 2.0.
      Nigeria and South Africa had the greatest absolute numbers of physicians and
      nephrologists but Mauritius had the greatest proportion to population. South
      Africa had the most dialysis patients. Kenya, Nigeria and South Africa were the
      only countries with RTx programs and reported rates per million population of
      0.60, 0.23 and 5.12, respectively. Treatment for patients with CKD in SSA is
      limited by a lack of physicians, nephrologists, and dialysis centers. Few
      countries are performing RTx. Resources are needed to increase the health
      workforce and increase RTx programs in SSA.

PMID- 22458853
TI  - In vivo efficacy of the histone deacetylase inhibitor suberoylanilide hydroxamic
      acid in combination with radiotherapy in a malignant rhabdoid tumor mouse model.
AB  - PURPOSE: Histone deacetylase inhibitors are promising new substances in cancer
      therapy and have also been shown to sensitize different tumor cells to
      irradiation (XRT). We explored the effect as well as the radiosensitizing
      properties of suberoylanilide hydroxamic acid (SAHA) in vivo in a malignant
      rhabdoid tumor (MRT) mouse model. METHODS AND MATERIAL: Potential
      radiosensitization by SAHA was assessed in MRT xenografts by analysis of tumor
      growth delay, necrosis (HE), apoptosis (TUNEL), proliferation (ki-67) and
      gammaH2AX expression as well as dynamic 18F-Fluorodeoxyglucose Positron Emission
      Tomography (18F-FDG -PET) after treatment with either SAHA alone, single-dose (10
      Gy) or fractionated XRT (3 * 3Gy) solely as well as in combination with SAHA
      compared to controls. RESULTS: SAHA only had no significant effect on tumor
      growth. Combination of SAHA for 8 days with single-dose XRT resulted in a higher
      number of complete remissions, but failed to prove a significant growth delay
      compared to XRT only. In contrast fractionated XRT plus SAHA for 3 weeks did
      induce significant tumor growth delay in MRT-xenografts. The histological
      examination showed a significant effect of XRT in tumor necrosis, expression of
      Ki-67, gammaH2AX and apoptosis. SAHA only had no significant effect in the
      histological examination. Comparison of xenografts treated with XRT and XRT plus
      SAHA revealed a significantly increased gammaH2AX expression and apoptosis
      induction in the mice tumors after combination treatment with single-dose as well
      as fractionated XRT. The combination of SAHA with XRT showed a tendency to
      increased necrosis and decrease of proliferation compared to XRT only, which,
      however, was not significant. The 18F-FDG-PET results showed no significant
      differences in the standard uptake value or glucose transport kinetics after
      either treatment. CONCLUSION: SAHA did not have a significant effect alone, but
      proved to enhance the effect of XRT in our MRT in vivo model.

PMID- 22458854
TI  - Motivation and parental presence during induction of anesthesia: an examination
      of the role of ethnicity and language.
AB  - OBJECTIVES: To examine the role of ethnicity and language in parental desire and
      motivation to be present for children's anesthesia induction. AIM: To compare
      motivation for parental presence at induction of anesthesia (PPIA) between
      English- and Spanish-speaking White and Hispanic parents of children undergoing
      outpatient surgery. BACKGROUND: The effectiveness of PPIA may depend, in part, on
      parental motivation and desire to be present at children's anesthesia induction;
      however, cultural variables such as ethnicity and language have not previously
      been explored in this relationship. METHODS/MATERIALS: Participants included 258
      parents of children undergoing outpatient surgery and general anesthesia. Parents
      were grouped by self-reported ethnicity and primary language spoken into English
      speaking White (ESW, n = 55), English-speaking Hispanic (ESH, n = 108), and
      Spanish-speaking Hispanic (SPH, n = 95) groups. Measures included the Motivation
      for Parental Presence during Induction of Anesthesia (MPPIA) and a 4-item measure
      of preference for PPIA. RESULTS: The majority of parents (73%) expressed a
      preference for PPIA. Analyses controlling for group differences in socioeconomic
      status and demographic variables revealed that English-(P = 0.03) and Spanish
      speaking (P = 0.06) Hispanic parents reported significantly greater levels of
      desire to be present for their child's anesthesia induction compared to English
      speaking White parents. English-speaking Hispanic parents also reported greater
      levels of beliefs about the impact of anxiety on children's anesthesia induction
      compared to English-speaking White parents (P = 0.07). CONCLUSIONS: Parental
      ethnicity and language may impact desire and motivation for PPIA, which may
      subsequently impact the effectiveness of PPIA and child anxiety at anesthesia
      induction. Future research should examine the impact of parental characteristics,
      including cultural variables, on children's preoperative anxiety.

PMID- 22458855
TI  - Phototoxicity and environmental transformation of polycyclic aromatic
      hydrocarbons (PAHs)-light-induced reactive oxygen species, lipid peroxidation,
      and DNA damage.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a class of mutagenic and tumorigenic
      environmental contaminants. Although the mechanisms by which PAHs induce cancer
      in experimental animals have been extensively studied and the metabolic
      activation pathways have been determined, the environmental fate of PAHs and the
      phototoxicity exerted by PAHs, as well as their photoreaction products formed in
      the environment, have received much less attention. In this review, the formation
      of oxygenated PAHs, PAH quinones, nitro-PAHs, and halogenated PAHs from
      photoreaction of environmental PAHs are addressed. Upon light irradiation, PAHs
      and all PAH photoreaction products can absorb light energy to reach photo-excited
      states, which react with molecular oxygen, medium, and coexisting chemicals to
      produce reactive oxygen species (ROS) and other reactive intermediates, such as
      oxygenated PAHs and free radicals. These intermediates, including ROS, induce
      lipid peroxidation, and DNA damage including DNA strand breakage, oxidation to 8
      oxo-2'-deoxyguanosine, and DNA-adducts. Since these toxicological endpoints are
      associated with age-related diseases, including cancer, environmental PAHs
      concomitantly exposed to sunlight may potentially promote human skin damage,
      leading to ageing and skin cancers. Thus, we suggest that (i) in addition to the
      widely recognized metabolic pathways, more attention must be paid to
      photoreaction as an important activation pathway for PAHs, (ii) risk assessment
      of environmental PAHs should take into consideration the complex photochemical
      reactions leading to mixtures of products that are also phototoxic; and (iii) the
      study of structure-toxicity relationships should be expanded to cover the complex
      photoreactions and extrinsic factors that affect phototoxicity endpoints.

PMID- 22458856
TI  - Physical and physicochemical factors effecting transport of chlorohydrocarbon
      gases from lung alveolar air to blood as measured by the causation of narcosis.
AB  - This systematic investigation examines gas transport in the lung for two sets of
      chlorohydrocarbons (CHCs): the chloromethanes (C1) and chloroethanes (C2). The C1
      series includes chloromethane, methylene chloride, chloroform, and carbon
      tetrachloride, and the C2 series includes chloroethane, 1,2-dichloroethane, 1, 1,
      2-trichloroethane, and 1, 1, 2, 2-tetrachloroethane. Most CHC gases cause
      narcosis. The comprehensive narcosis work of Lehmann and colleagues on CHCs was
      used as a basis for the narcosis endpoint in the present examination. The sites
      for narcosis are located in the brain (midline cortex and posterior parietal
      area), the spine, and at many peripheral nerve sites. Central nervous system
      (CNS) exposure executes a multisite, neural transmission set of inhibitions that
      promotes rapid loss of consciousness, sensory feeling, and current and stored
      memory while providing temporary amnesia. Absorption into the system requires
      dissolution into many lipid membranes and binding to lipoproteins. Lipophilicity
      is a CHC property shared with many anesthetics according to the Meyer-Overton
      Rule. Many structurally different lipid chemicals produce the narcosis response
      when the lipid concentration exceeds -67 mM. This suggests narcotic or anesthetic
      dissolution into CNS membranes until the lipid organization is disrupted or
      perturbed. This perturbation includes loading of Na(+)- and K(+)-channel
      transmembrane lipoprotein complexes and disrupting their respective channel
      functional organizations. The channel functions become attenuated or abrogated
      until the CHC exposure ceases and CHC loading reverses. This investigation
      demonstrates how the CHC physical and chemical properties influence the
      absorption of these CHCs via the lung and the alveolar system on route to the
      blood. Narcosis in test animals was used here as an objective biological endpoint
      to study the effects of the physical factors Bp, Vp, Kd (oil: gas) partition,
      Henry's constant (HK), and water solubility (S%) on gas transport. Narcosis is
      immediate after gas exposure and requires no chemical activation only absorption
      into the blood and circulation to CNS narcotic sites. The three physical factors
      Bp, K(d) (oil: air), and S% vary directly with unitary narcosis (UN) whereas Vp
      and HK vary inversely with UN in linear log-log relationships for the C2 series
      but not for the C1 series. Physicochemical properties of C1 series gases indicate
      why they depart from what is usually assumed to be an Ideal Gas. An essential
      discriminating process in the distal lung is the limiting alveolar film layer
      (AFL) and the membrane layer of the alveolar acini. The AFL step influences gas
      uptake by physically limiting the absorption process. Interaction with and
      dissolution into aqueous solvent of the AFL is required for transport and
      narcotic activity. Narcotics or anesthetics must engage the aqueous AFL with
      sufficient strength to allow transport and absorption for downstream CNS binding.
      CHCs that do not engage well with the AFL are not narcotic. Lipophilicity and
      amphipathicity are also essential solvency properties driving narcotics'
      transport through the alveolar layer, delivery to the blood fats and
      lipoproteins, and into critical CNS lipids, lipoproteins, and receptor sites that
      actuate narcosis. AFL disruption is thought to be strongly related to a number of
      serious pulmonary diseases such acute respiratory distress syndrome, infant
      respiratory distress syndrome, emphysema, chronic obstructive pulmonary disease,
      asthma, chronic bronchitis, pneumonia, pulmonary infections, and idiopathic
      pulmonary fibrosis. The physical factors (Bp, Vp, Kd [oil: gas] partition,
      Henry's constant, and water solubility [S%]) combine to affect a specific
      transport through the AFL if lung C > C(0) (threshold concentration for
      narcosis). The degree of blood CHC absorption depends on dose, lipophilicity, and
      lung residence time. AFL passage can be manipulated by physical factors of
      increased pressure (kPa) or increased gas exposure (moles). Molecular
      lipophilicity facilitates narcosis but lipophilicity alone does not explain
      narcosis. Vapor pressure is also required for narcosis. Narcotic activity
      apparently requires stereospecific processing in the AFL and/or down-stream
      inhibition at stereospecific lipoproteins at CNS inhibitory sites. It is proposed
      that CHCs likely cannot proceed through the AFL without perturbation or
      disruption of the integrity of the AFL at the alveoli. CHC physicochemical
      properties are not expected to allow their transport through the AFL as
      physiological CO(2) and O(2) naturally do in respiration. This work considers CHC
      inspiration and systemic absorption into the blood with special emphasis on the
      CHC potential perturbation effects on the lipid, protein liquid layer supra to
      the alveolar membrane (AFL). A heuristic gas transport model for the CHCs is
      presented as guidance for this examination. The gas transport model can be used
      to study absorption for other gas delivery endpoints of environmental concern
      such as carcinogens.

PMID- 22458857
TI  - Extrapolation of hypothalamic-pituitary-thyroid axis perturbations and associated
      toxicity in rodents to humans: case study with perchlorate.
AB  - Functional aspects of the Hypothalamic-Pituitary-Thyroid (HPT) axis in rats and
      humans are compared, exposing why extrapolation of toxicant-induced perturbations
      in the rat HPT axis to the human HPT axis cannot be accomplished using default
      risk assessment methodology. Computational tools, such as biologically based dose
      response models for the HPT axis, are recommended to perform complex animal to
      human extrapolations involving the HPT axis. Experimental and computational
      evidence are presented that suggest perchlorate acts directly on the thyroid
      gland in rats. The apparent escape from perchlorate-induced inhibition of
      thyroidal uptake of radioactive iodide in humans is discussed along with
      "rebound" or increased thyroidal uptake of radioactive iodide observed after
      discontinued clinical treatment with perchlorate.

PMID- 22458858
TI  - Overdose deaths demand a new paradigm for opioid rotation.
AB  - OBJECTIVE: An increasing number of deaths have been inferred to be associated
      with current opioid rotation practices and evidence is mounting that the use of
      widely accepted protocols for opioid rotation is an important contributing
      factor. Based on the findings of a literature review published in conjunction
      with this article, we propose a new paradigm for a potentially safer method of
      opioid rotation and present a case study illustrating the paradigm. This new
      paradigm suggests three easy-to-remember steps in opioid rotation and obviates
      the need to use a conversion table. DESIGN: Report of a clinical case of a
      patient undergoing opioid rotation using this new paradigm. SUMMARY: The patient
      was successfully rotated from extended-release oxycodone to extended-release
      hydromorphone. The dose of oxycodone was slowly decreased, while the
      hydromorphone dose was slowly titrated. A critical element to this approach
      involved providing sufficient immediate-release opioid to treat breakthrough pain
      and to reverse acute abstinence signs and symptoms if the dosing changes prove
      insufficient. CONCLUSION: A safer new paradigm for opioid rotation may provide an
      important incremental step forward in reducing adverse public health consequences
      of inappropriate opioid dosing.

PMID- 22458859
TI  - Phylogenetic diversity of the dddP gene for dimethylsulfoniopropionate-dependent
      dimethyl sulfide synthesis in mangrove soils.
AB  - The dddP gene encodes an enzyme that cleaves dimethylsulfoniopropionate (DMSP)
      into dimethyl sulfide (DMS) plus acrylate and has been identified in various
      marine bacteria and some fungi. The diversity of dddP genes was investigated by
      culture-independent PCR-based analysis of metagenomic DNA extracted from 4
      mangrove soils in Southern China. A phylogenetic tree of 144 cloned dddP
      sequences comprised 7 groups, 3 of which also included dddP genes from previously
      identified Ddd(+) (DMSP-dependent DMS production) bacteria. However, most (69%)
      of the DddP sequences from the mangroves were in 4 other subgroups that did not
      include sequences from known bacteria, demonstrating a high level of diversity of
      this gene in these environments. Each clade contained clones from all of the
      sample sites, suggesting that different dddP types are widespread in mangroves of
      different geographical locations. Furthermore, it was found the dddP genotype
      distribution was remarkably influenced by the soil properties pH, available
      sulfur, salt, and total nitrogen.

PMID- 22458861
TI  - Estimation of size-resolved ambient particle density based on the measurement of
      aerosol number, mass, and chemical size distributions in the winter in Beijing.
AB  - Simultaneous measurements of aerosol size, distribution of number, mass, and
      chemical compositions were conducted in the winter of 2007 in Beijing using a
      Twin Differential Mobility Particle Sizer and a Micro Orifice Uniform Deposit
      Impactor. Both material density and effective density of ambient particles were
      estimated to be 1.61 +/- 0.13 g cm(-3) and 1.62 +/- 0.38 g cm(-3) for PM(1.8) and
      1.73 +/- 0.14 g cm(-3) and 1.67 +/- 0.37 g cm(-3) for PM(10). Effective density
      decreased in the nighttime, indicating the primary particles emission from coal
      burning influenced the density of ambient particles. Size-resolved material
      density and effective density showed that both values increased with diameter
      from about 1.5 g cm(-3) at the size of 0.1 MUm to above 2.0 g cm(-3) in the
      coarse mode. Material density was significantly higher for particles between 0.56
      and 1.8 MUm during clean episodes. Dynamic Shape Factors varied within the range
      of 0.95-1.13 and decreased with particle size, indicating that coagulation and
      atmospheric aging processes may change the shape of particles.

PMID- 22458860
TI  - Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium
      falciparum malaria in India.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) has been recommended for
      the treatment of falciparum malaria by the World Health Organization. Though
      India has already switched to ACT for treating falciparum malaria, there is need
      to have multiple options of alternative forms of ACT. A randomized trial was
      conducted to assess the safety and efficacy of the fixed dose combination of
      artesunate-amodiaquine (ASAQ) and amodiaquine (AQ) for the treatment of
      uncomplicated falciparum malaria for the first time in India. The study sites are
      located in malaria-endemic, chloroquine-resistant areas. METHODS: This was an
      open label, randomized trial conducted at two sites in India from January 2007 to
      January 2008. Patients between six months and 60 years of age having Plasmodium
      falciparum mono-infection were randomly allocated to ASAQ and AQ arms. The
      primary endpoint was 28-day PCR-corrected parasitological cure rate. RESULTS:
      Three hundred patients were enrolled at two participating centres, Ranchi,
      Jharkhand and Rourkela, Odisha. Two patients in AQ arm had early treatment
      failure while there was no early treatment failure in ASAQ arm. Late treatment
      failures were seen in 13 and 12 patients in ASAQ and AQ arms, respectively. The
      PCR-corrected cure rates in intent-to-treat population were 97.51% (94.6-99.1%)
      in ASAQ and 88.65% (81.3-93.9%) in AQ arms. In per-protocol population, they were
      97.47% (94.2-99.2%) and 88.30% (80-94%) in ASAQ and AQ arms respectively. Seven
      serious adverse events (SAEs) were reported in five patients, of which two were
      reported as related to the treatment. All SAEs resolved without sequel.
      CONCLUSION: The fixed dose combination of ASAQ was found to be efficacious and
      safe treatment for P. falciparum malaria. Amodiaquine also showed acceptable
      efficacy, making it a suitable partner of artesunate. The combination could prove
      to be a viable option in case India opts for fixed dose combination ACT. CLINICAL
      TRIAL REGISTRY: ISRCTN84408319.

PMID- 22458862
TI  - Automated texture recognition of quartz sand grains for forensic applications.
AB  - Quartz sand surface texture analysis has been automated for the first time for
      forensic application. The derived Basic Image Features (BIFs) provide computer
      generated texture recognition from preexisting data sets. The technique was
      applied to two distinct classification problems; first, the ability of the system
      to discriminate between (quartz) sand grains with upturned plate features
      (indicative of eolian, global sand sea environments) and grains that do not
      exhibit these features. A success rate of grain classification of 98.8% was
      achieved. Second, to test the ability of the computer recognition system to
      identify specific energy levels of formation of the upturned plate surface
      texture features. Such recognition ability has to date been beyond manual
      geological interpretation. The discrimination performance was enhanced to an
      exact classification success rate of 81%. The enhanced potential for routine
      forensic investigation of the provenance of common quartz sand is indicated.

PMID- 22458863
TI  - Characterization and gene expression analysis of the cir multi-gene family of
      Plasmodium chabaudi chabaudi (AS).
AB  - BACKGROUND: The pir genes comprise the largest multi-gene family in Plasmodium,
      with members found in P. vivax, P. knowlesi and the rodent malaria species.
      Despite comprising up to 5% of the genome, little is known about the functions of
      the proteins encoded by pir genes. P. chabaudi causes chronic infection in mice,
      which may be due to antigenic variation. In this model, pir genes are called cirs
      and may be involved in this mechanism, allowing evasion of host immune responses.
      In order to fully understand the role(s) of CIR proteins during P. chabaudi
      infection, a detailed characterization of the cir gene family was required.
      RESULTS: The cir repertoire was annotated and a detailed bioinformatic
      characterization of the encoded CIR proteins was performed. Two major sub
      families were identified, which have been named A and B. Members of each sub
      family displayed different amino acid motifs, and were thus predicted to have
      undergone functional divergence. In addition, the expression of the entire cir
      repertoire was analyzed via RNA sequencing and microarray. Up to 40% of the cir
      gene repertoire was expressed in the parasite population during infection, and
      dominant cir transcripts could be identified. In addition, some differences were
      observed in the pattern of expression between the cir subgroups at the peak of P.
      chabaudi infection. Finally, specific cir genes were expressed at different time
      points during asexual blood stages. CONCLUSIONS: In conclusion, the large number
      of cir genes and their expression throughout the intraerythrocytic cycle of
      development indicates that CIR proteins are likely to be important for parasite
      survival. In particular, the detection of dominant cir transcripts at the peak of
      P. chabaudi infection supports the idea that CIR proteins are expressed, and
      could perform important functions in the biology of this parasite. Further
      application of the methodologies described here may allow the elucidation of CIR
      sub-family A and B protein functions, including their contribution to antigenic
      variation and immune evasion.

PMID- 22458864
TI  - Antidepressant-like activity of gallic acid in mice subjected to unpredictable
      chronic mild stress.
AB  - This study was designed to evaluate antidepressant-like activity of gallic acid
      in Swiss young male albino mice subjected to unpredictable chronic mild stress
      and to explore the possible underlying mechanisms for this activity. Gallic acid
      (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered
      daily to unstressed mice and other groups of mice subjected to unpredictable mild
      stress, 30 min after the injection for 21 successive days. The antidepressant
      like activity was evaluated using forced swim test (FST) and sucrose preference
      test. Stress significantly increased immobility period of mice in FST. Gallic
      acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility
      period of unstressed and stressed mice in FST and prevented the stress-induced
      decrease in sucrose preference, indicating significant antidepressant-like
      activity. There was no significant effect on locomotor activity of the mice by
      the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine
      oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in
      unstressed mice; and significantly prevented the stress-induced decrease in
      reduced glutathione and catalase activity; and also significantly prevented
      stress-induced increase in MAO-A activity, malondialdehyde levels, plasma
      nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like
      activity in unstressed and stressed mice probably due to its antioxidant activity
      and through inhibition of MAO-A activity and decrease in plasma nitrite levels.
      In addition, gallic acid also showed antidepressant-like activity in stressed
      mice probably through decrease in plasma corticosterone levels. 

PMID- 22458866
TI  - Comparison of conventional and digital radiography systems with regard to
      radiopacity of root canal filling materials.
AB  - AIM: To compare the radiopacity of five root filling materials as measured on
      digitized E-speed films, storage phosphor plate and CCD sensor images.
      METHODOLOGY: Radiopacity of Resilon cones and Epiphany, MM-Seal, EndoREZ and AH
      Plus sealers were investigated. Ten acrylic plates were prepared and filled with
      the materials. Samples were radiographed together with samples of dentine and an
      aluminium stepwedge. Images were obtained using E-speed films, Digora storage
      phosphor plates and Schick CDR CCD sensor. Conventional radiographs were
      digitized using a desktop scanner. Mean grey values of the materials, stepwedge
      and dentine were measured using the histogram analysis function of Photoshop 7.0.
      A graph of radiographic density versus thickness of the aluminium was drawn for
      each image from which the radiographic densities of the materials were determined
      in relation to the aluminium thickness. The mean was calculated, and the data
      were analysed using repeated measures anova and Bonferroni tests (P<0.05).
      RESULTS: There were significant differences between different imaging modalities
      (P=0.018) and root filling materials (P<0.001). A statistically significant
      interaction between imaging modality and material was also observed (P<0.001).
      All materials had radiopacity above 3mm of aluminium regardless of the imaging
      technique. The radiopacity of Resilon and Epiphany was significantly higher on
      digital images compared with digitized E-speed film images (P<0.001). CONCLUSION:
      The choice of imaging system may effect radiopacity measurements. It is possible
      that radiopacity as recorded on traditional or digitized films is not indicative
      of the radiopacity as recorded on a digital sensor.

PMID- 22458867
TI  - From dysfunction to adaptation: an interactionist model of dependency.
AB  - Contrary to clinical lore, a dependent personality style is associated with
      active as well as passive behavior and may be adaptive in certain contexts (e.g.,
      in fostering compliance with medical and psychotherapeutic treatment regimens).
      The cognitive/interactionist model conceptualizes dependency-related responding
      in terms of four components: (a) motivational (a marked need for guidance,
      support, and approval from others); (b) cognitive (a perception of oneself as
      powerless and ineffectual); (c) affective (a tendency to become anxious when
      required to function autonomously); and (d) behavioral (use of diverse self
      presentation strategies to strengthen ties to potential caregivers). Clinicians'
      understanding of the etiology and dynamics of dependency has improved
      substantially in recent years; current challenges include delineating useful
      subtypes of dependency, developing valid symptom criteria for Dependent
      Personality Disorder in DSM-5 and beyond, and working effectively with dependent
      patients in the age of managed care.

PMID- 22458865
TI  - A randomized controlled trial on the effectiveness of strength training on
      clinical and muscle cellular outcomes in patients with prostate cancer during
      androgen deprivation therapy: rationale and design.
AB  - BACKGROUND: Studies indicate that strength training has beneficial effects on
      clinical health outcomes in prostate cancer patients during androgen deprivation
      therapy. However, randomized controlled trials are needed to scientifically
      determine the effectiveness of strength training on the muscle cell level.
      Furthermore, close examination of the feasibility of a high-load strength
      training program is warranted. The Physical Exercise and Prostate Cancer (PEPC)
      trial is designed to determine the effectiveness of strength training on clinical
      and muscle cellular outcomes in non-metastatic prostate cancer patients after
      high-dose radiotherapy and during ongoing androgen deprivation therapy.
      METHODS/DESIGN: Patients receiving androgen deprivation therapy for 9-36 months
      combined with external high-dose radiotherapy for locally advanced prostate
      cancer are randomized to an exercise intervention group that receives a 16 week
      high-load strength training program or a control group that is encouraged to
      maintain their habitual activity level. In both arms, androgen deprivation
      therapy is continued until the end of the intervention period.Clinical outcomes
      are body composition (lean body mass, bone mineral density and fat mass) measured
      by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning
      (muscle strength and cardio-respiratory fitness) assessed with physical tests and
      psycho-social functioning (mental health, fatigue and health-related quality of
      life) assessed by questionnaires. Muscle cellular outcomes are a) muscle fiber
      size b) regulators of muscle fiber size (number of myonuclei per muscle fiber,
      number of satellite cells per muscle fiber, number of satellite cells and
      myonuclei positive for androgen receptors and proteins involved in muscle protein
      degradation and muscle hypertrophy) and c) regulators of muscle fiber function
      such as proteins involved in cellular stress and mitochondrial function. Muscle
      cellular outcomes are measured on muscle cross sections and muscle homogenate
      from muscle biopsies obtained from muscle vastus lateralis. DISCUSSION: The
      findings from the PEPC trial will provide new knowledge on the effects of high
      load strength training on clinical and muscle cellular outcomes in prostate
      cancer patients during androgen deprivation therapy. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00658229.

PMID- 22458868
TI  - Personality disorders in DSM-5.
AB  - A substantive revision of the Diagnostic and Statistical Manual of Mental
      Disorders (DSM) last occurred in 1994; therefore, the mental health field should
      anticipate significant changes to the classification of mental disorders in the
      fifth edition. Since DSM-5 Work Groups have recently proposed revisions for the
      major diagnostic classes of mental disorders, an article on the current status of
      the personality disorders (PDs) is timely. This article reviews scientific
      principles that have influenced the development of proposed changes for the
      assessment and diagnosis of personality psychopathology in DSM-5, presents the
      proposed model as of the summer of 2011, summarizes rationales for the changes,
      and discusses critiques of the model. Scientific principles were articulated for
      DSM-5 more than a decade ago; their application to the process has not been
      straightforward, however. Work Group members have labored to improve the DSM-5
      approach to personality and PDs to make the classification more valid and more
      clinically useful. The current model continues to be a work in progress.

PMID- 22458869
TI  - von Willebrand factor: demographics of plasma protein level in a large blood
      donor cohort from South Wales in the United Kingdom.

PMID- 22458870
TI  - A before and after study assessing the impact of a new model for recognizing and
      responding to early signs of deterioration in an acute hospital.
AB  - AIM: To evaluate the impact of a new model for the detection and management of
      deteriorating patients on knowledge and confidence of nursing staff in an acute
      hospital. BACKGROUND: International evidence shows that clinical deterioration is
      not always recognized or acted on by nurses. The use of physiological track and
      trigger scoring systems accompanied by a graded response strategy has been
      recommended to monitor all adult patients in acute UK hospitals. However, little
      is known about the impact of these new systems in practice. DESIGN: A single
      centre, mixed methods before-and-after study. METHODS: A mixed methods before-and
      after study, set in a district general hospital in England, in 2009, including a
      survey (n = 213) and qualitative interviews (n = 15) with nursing staff. The
      questionnaire examined knowledge and confidence in recognition and management of
      deteriorating patients 6 weeks before and after an intervention which included
      training, new observation charts and a new track and trigger system. Interviews
      further explored participants' perspectives. Comparisons were made between
      registered and unregistered nurses. RESULTS: Following the intervention,
      knowledge, and confidence to recognize and manage deteriorating patients
      increased; the number of concerns were reduced. Scores were higher for registered
      than unregistered nurses before and after the intervention. Interviews confirmed
      these findings and provided detail on how nurses felt the new system had improved
      practice. CONCLUSION: The new model had a positive impact on the self-assessed
      knowledge and confidence of registered and unregistered nurses. Similar
      initiatives should take into account the clinical context and tailor training
      packages accordingly.

PMID- 22458871
TI  - Characterisation of forces exerted by the entire hand during the power grip:
      effect of the handle diameter.
AB  - The objective of this study was to analyse the effect of the handle diameter on
      the grip forces exerted by the hand during a maximal power grip task. A handle
      ergometer, combining six instrumented beams and a pressure map, was used to
      determine the forces exerted by the palm side of the hand regrouping data from 10
      anatomical sites (fingertips, phalanges, thumb, palm...). This methodology
      provided results giving new insight into the effect of the handle diameter on the
      forces exerted by the hand. First, it appeared that the relationship between the
      hand length/handle diameter ratio and the maximal grip force fit a U-inverted
      curve with maximal values observed for a handle diameter measuring 17.9% of the
      hand length. Second, it was showed that the handle diameter influenced the forces
      exerted on the anatomical sites of the hand. Finally, it was showed that the
      handle diameter influenced the finger force sharing particularly for the index
      and the little fingers.    Practitioner Summary: This study analysed the effect
      of the handle diameter on the grip forces exerted by the hand during a maximal
      power grip force. This study showed that measurement of the totality of the
      forces exerted at the hand/handle interface is needed to better understand the
      ergonomics of handle tools. Our results could be re-used by designers and
      clinicians in order to develop handle tools which prevent hand pathologies.

PMID- 22458872
TI  - Video preference assessment and behavioral management of single-caged Japanese
      macaques (Macaca fuscata) by movie presentation.
AB  - Movie presentation can act as an enrichment technique for nonhuman primates, who
      also show preferences for certain contents. This study investigated the video
      preferences and effects of movies on behavioral abnormalities in single-caged
      Japanese macaques. When movie rewards were provided for subjects' touch
      responses, the subjects maintained the touch responses during 40 2-hr sessions.
      Although repeated presentation of 1 stimulus set decreased the subject's touch
      response, changing the stimulus set led to recovery of this response. The
      subjects showed clear preferences, consistent across 2 different stimulus sets,
      for movies showing humans or animation (61.1% of total duration). Subjects
      consistently played movies both with and without their preferred content. The
      availability of a variety of contents might be important for attracting subjects'
      interest. The frequency with which monkeys engaged in abnormal behaviors
      decreased in the experimental (20.9%) and the postexperimental (25.6%) periods
      compared with the preexperimental period (33.5%). Movie presentations could keep
      attracting the interest of single-caged monkeys in their visual environment,
      ameliorating their behavioral abnormalities for some time. In summary, social
      experience during infancy might influence Japanese macaques' movie preferences.

PMID- 22458873
TI  - Visitor influence on the behavior of captive greater rheas (Rhea americana,
      Rheidae Aves).
AB  - Visitors can affect and reduce the welfare of nonhuman animals. The Belo
      Horizonte Zoo, Brazil, had a group of greater rheas intended for reintroduction
      to the wild. Because this group received public visitation, evaluating its effect
      on the birds' behavior and welfare was important. The study conducted 60 hr of
      behavioral observations: 30 with, and 30 without, visitors in front of the birds'
      enclosure. The study, conducted April-December 2009, collected data using scan
      sampling with instantaneous recording of behavior every minute. The study
      collected data on public behavior, visitor density, and time spent observing the
      birds. More than 4,000 persons visited the birds' enclosure: 9.86 s average time
      spent. Public behaviors most expressed were walking-watching-talking and stopped
      watching-talking; visitors or not, greater rheas' most expressed behaviors
      (inversed between treatments) were foraging and walking alert;
      defecating/urinating and other behaviors differed statistically between
      treatments. Walking alert was most expressed in the presence of visitors;
      defecating/urinating and other behaviors were most expressed in their absence.
      Greater rheas seemed to habituate to visitors. Birds' behaviors differed little
      in visitors' presence or absence.

PMID- 22458874
TI  - Pair housing for female longtailed and rhesus macaques in the laboratory:
      behavior in protected contact versus full contact.
AB  - Pair housing for caged macaques in the laboratory generally allows unrestricted
      tactile contact but, less commonly, may involve limited contact via grooming
      contact bars or perforated panels. The purpose of using this protected contact
      housing, which prevents entry into pair-mates' cages, typically is to accommodate
      research and management requirements. The study used behavioral data collected on
      12 pairs of female longtailed macaques (Macaca fascicularis) at the Washington
      National Primate Research Center and 7 pairs of female rhesus macaques (Macaca
      mulatta) housed at the Tulane National Primate Research Center to assess the
      relative benefits of protected versus full protected contact. The study collected
      data in stable pairs housed first in protected contact followed by full contact.
      Species combined, the study found the presence of the panel was associated with
      lower levels of social grooming and higher levels of self-grooming, abnormal
      behavior, and tension-related behavior. Within species, only the protected-
      versus full-contact contrasts for abnormal and tension were statistically
      significant-and only for rhesus macaques. Results suggest that for female rhesus
      macaques, potential disadvantages or inconveniences of full contact should be
      balanced against the improved behavioral profile in comparison to protected
      contact. The use of protected contact among female longtailed macaques does not
      appear to require the same cost-benefit analysis.

PMID- 22458875
TI  - Development and validation of a behavioral acclimation protocol for cats to
      respiration chambers used for indirect calorimetry studies.
AB  - Cats exposed to novel environments initiate stress responses by behavioral and
      physiological changes that modify metabolism and lead to the collection of
      unreliable data. Fourteen cats (10 +/- 2 months) were subjected to an 11-week
      acclimation procedure to adapt to restriction within chambers used for indirect
      calorimetry studies. Cats were acclimated to chambers in their home environments,
      to chambers in the study room, and to increasing periods of restriction within
      chambers. Ten additional cats (11 +/- 1 month), used as controls, were subjected
      to a single 5-hr restriction without any prior exposure. Stress level, feed
      intake, fearfulness, and eliminations were recorded. Latencies to approach a
      novel object peaked on Weeks 4 and 8 (p < .05). Cat-Stress-Scores (CSS) declined
      with exposure and on Week 11, stress levels were low and consistent (p < .05).
      CSS was greater in unacclimated versus acclimated cats (p < .05). In conclusion,
      acclimation protocols prepare cats for repeated, temporary restriction within
      chambers, whereas short acclimations do not. A step-up acclimation procedure with
      behavioral indices of stress should be utilized to prepare cats for research that
      necessitates restriction.

PMID- 22458876
TI  - Increasing the frequency of co-mingling piglets during the lactation period
      alters the development of social behavior before and after weaning.
AB  - The purpose of this study was to determine how increasing the frequency of co
      mingling affected piglets' behavior development before and after weaning. Co
      mingling once (CM1), piglets interacted with 1 unfamiliar litter Days 10-18 after
      birth; co-mingling twice (CM2), piglets interacted with 1 unfamiliar litter Days
      10-14; and with another, Days 14-18. Control (CM0) piglets did not interact with
      unfamiliar litters before Day 18 (n = 16 litters per treatment). The study
      weighed piglets and recorded ear-injury scores throughout the experiment;
      however, there were no treatment differences. The CM2 piglets spent less time
      engaged in aggressive interactions (p < .05) than did CM0 piglets following
      mixing at weaning. During the social challenge, CM2 piglets spent more time in
      proximity to one another, had shorter latencies to first aggressive interaction,
      and spent less time fighting than did CM0 piglets (p < .05). During the social
      recognition test, CM2 piglets recognized the stimulus piglet at a faster rate
      than did CM0 piglets (p < .05). Overall, CM2 resulted in changes to some social
      behaviors compared with CM0 but not with CM1.

PMID- 22458877
TI  - Pedigree dog "Exposed": a documentary.

PMID- 22458880
TI  - Nicorandil: from ulcer to fistula into adjacent organs.
AB  - Nicorandil is an original vasodilatator used to control angina by decreasing
      cardiac preload and afterload. Since 1997, many reports of single or multiple
      nicorandil-induced ulcerations have been published. To date, eight cases of
      nicorandil-induced fistula into adjacent organs have been described. The
      pathogeneses of nicorandil-induced ulceration and fistula into adjacent organs
      are not yet elucidated. The two main hepatic biotransformation pathways of
      nicorandil are denitration and reduction of the alkyl chain leading to
      nicotinamide and niconitic acid which merge into the endogenous pool of
      nicotinamide adenine dinucleotide/phosphate. This merging which is known as
      saturable, may contribute to a slow and abnormal distribution of nicotinamide and
      nicotinic acid out of the endogenous pool. Under these special conditions,
      providing these two molecules in situ, nicotinic acid associated with
      nicotinamide may ulcerate rather recent or maintained trauma. Ulcers and fistulae
      induced by nicorandil heal after withdrawal. Surgical intervention is unnecessary
      and inappropriate as it is ineffective and exacerbates morbidity. All
      practitioners should be correctly informed about these serious but preventable
      nicorandil side effects, which mostly occur in the elderly and fragile
      population. In the absence of corrective measures, withdrawal of this original
      and active drug should be considered.

PMID- 22458881
TI  - Resistance to spiromesifen in Trialeurodes vaporariorum is associated with a
      single amino acid replacement in its target enzyme acetyl-coenzyme A carboxylase.
AB  - Spiromesifen is a novel insecticide and is classed as a tetronic acid derivative.
      It targets the insects' acetyl-coenzyme A carboxylase (ACCase) enzyme, causing a
      reduction in lipid biosynthesis. At the time of this publication, there are no
      reports of resistance to this class of insecticides in insects although
      resistance has been observed in several mite species. The greenhouse whitefly
      Trialeurodes vaporariorum (Westwood) is a serious pest of protected vegetable and
      ornamental crops in temperate regions of the world and spiromesifen is widely
      used in its control. Mortality rates of UK and European populations of T.
      vaporariorum to spiromesifen were calculated and up to 26-fold resistance was
      found. We therefore sought to examine the molecular mechanism underlying
      spiromesifen resistance in this important pest. Pre-treatment with piperonyl
      butoxide did not synergize spiromesifen, suggesting a target-site resistance
      mechanism. The full length ACCase gene was sequenced for a range of T.
      vaporariorum strains and a strong association was found between spiromesifen
      resistance and a glutamic acid substitution with lysine in position 645 (E645K)
      of this gene. A TaqMan allelic discrimination assay confirmed these findings.
      Although this resistance is not considered sufficient to compromise the field
      performance of spiromesifen, this association of E645K with resistance is the
      first report of a potential target site mechanism affecting an ACCase inhibitor
      in an arthropod species.

PMID- 22458882
TI  - L105K mutant of proteorhodopsin.
AB  - Proteorhodopsin (PR) is a light-driven proton pump found in marine bacteria.
      Thousands of PRs are classified into blue-absorbing (lambda(max) ~ 490 nm) and
      green-absorbing (lambda(max) ~ 525 nm) PR, and the color determinant is known to
      be at position 105, where blue-absorbing and green-absorbing PR possess Gln and
      Leu, respectively. Position 105 is in contact with the retinal chromophore in the
      hydrophobic region of the cytoplasmic side. In this paper, we have introduced a
      positively charged lysine group at position 105, which is the first report of the
      introduction of a positively charged group into the hydrophobic cytoplasmic
      domain in microbial rhodopsins. The L105K mutant PR shows an ~21 nm red shift
      (lambda(max) ~ 549 nm) at pH 7.0, and the pK(a) of the counterion (7.2) does not
      change significantly compared to that of wild-type PR (6.8). The analysis of
      thermal stability shows that the mutation causes some destabilization of
      structure, but the mutant is more stable toward hydroxylamine reaction than the
      wild type. The flash photolysis measurement at pH 9.0 shows that the decay of the
      M intermediate of L105K is ~3 times slower than that of the wild type. The slow M
      decay possibly originates from the perturbation of the proton donor (Glu108) and
      the retinal Schiff base due to positioning of a positively charged lysine group
      in the proton transfer pathway. The perturbation of proton transport is also
      observed when we measure light-induced proton pumping. The rate of proton
      transport in L105K mutant is 6 times slower than that of the wild type, which
      corroborates our flash photolysis result.

PMID- 22458883
TI  - Hepatosplenic candidiasis in the era of new antifungal drugs: a study in Paris
      2000-2007.
AB  - We report a retrospective study of 24 patients with haematological malignancy and
      hepatosplenic candidiasis. Clinical and biological features were similar to
      previous reports. No patient previously received antifungal prophylaxis. Liver or
      spleen histological examination revealed yeasts in 6/24 patients (25%) on direct
      examination but all cultures were negative. After a median duration of 7 months,
      antifungal treatment was discontinued in 58% of the patients with no relapse.
      Eleven (46%) patients died during follow up. After multivariate analysis,
      independent factors associated with death were the duration of neutropenia (p
      0.022) and relapsing haematological malignancy (p 0.015).

PMID- 22458884
TI  - Review and critique of opioid rotation practices and associated risks of
      toxicity.
AB  - OBJECTIVES: A dramatic increase in unintentional deaths from opioids has occurred
      over the past decade with strong inference that many of these deaths may be
      resulting from prescriber's error. Recent evidence suggests that the use of dose
      conversion ratios published in equianalgesic tables may lead to fatal or near
      fatal opioid overdoses. The objective of this review was to determine whether the
      current practice of opioid rotation may be contributing to high rate of
      unintentional deaths. METHODS: We performed a focused literature review to
      identify reports of fatal or near-fatal outcomes that have occurred in
      conjunction with opioid rotation, to evaluate clinician competence in opioid
      rotation, and to identify inconsistencies in published protocols for opioid
      rotation. Further information was obtained by reviewing dosing instructions
      contained in product labels for extended-release formulations of several opioids.
      RESULTS: An increasing body of literature suggests that widely used opioid
      rotation practices, including the use of dose conversion ratios found in
      equianalgesic tables, may be an important contributor to the increasing incidence
      of opioid-related fatalities. These errors may be due, in part, not only to
      inadequate prescriber's competence but also to proliferation of inconsistent
      guidelines for opioid rotation, conflation of equianalgesic tables as conversion
      tables, and limitations inherent in the equianalgesic dose tables. CONCLUSIONS:
      Most of the fatal outcomes occurring during opioid rotation are preventable. The
      current process being used for opioid rotation has important flaws that must be
      corrected.

PMID- 22458885
TI  - Dynamic passive dosing for studying the biotransformation of hydrophobic organic
      chemicals: microbial degradation as an example.
AB  - Biotransformation plays a key role in hydrophobic organic compound (HOC) fate,
      and understanding kinetics as a function of (bio)availability is critical for
      elucidating persistence, accumulation, and toxicity. Biotransformation mainly
      occurs in an aqueous environment, posing technical challenges for producing
      kinetic data because of low HOC solubilities and sorptive losses. To overcome
      these, a new experimental approach based on passive dosing is presented. This
      avoids using cosolvent for introducing the HOC substrate, buffers substrate
      depletion so biotransformation is measured within a narrow and defined dissolved
      concentration range, and enables high compound turnover even at low
      concentrations to simplify end point measurement. As a case study, the
      biodegradation kinetics of two model HOCs by the bacterium Sphingomonas
      paucimobilis EPA505 were measured at defined dissolved concentrations ranging
      over 4 orders of magnitude, from 0.017 to 658 MUg L(-1) for phenanthrene and from
      0.006 to 90.0 MUg L(-1) for fluoranthene. Both compounds had similar
      mineralization fluxes, and these increased by 2 orders of magnitude with
      increasing dissolved concentrations. First-order mineralization rate constants
      were also similar for both PAHs, but decreased by around 2 orders of magnitude
      with increasing dissolved concentrations. Dynamic passive dosing is a useful tool
      for measuring biotransformation kinetics at realistically low and defined
      dissolved HOC concentrations.

PMID- 22458886
TI  - A case of zosteriform nevus spilus with halo nevus.

PMID- 22458887
TI  - Comparison of accelerated partial breast irradiation via multicatheter
      interstitial brachytherapy versus whole breast radiation.
AB  - BACKGROUND: Brachytherapy as adjuvant treatment for early-stage breast cancer has
      become widely available and offers patients an expedited treatment schedule.
      Given this, many women are electing to undergo brachytherapy in lieu of standard
      fractionation radiotherapy. We compare outcomes between patients treated with
      accelerated partial breast irradiation (APBI) via multicatheter interstitial
      brachytherapy versus patients who were also eligible for and offered APBI but who
      chose whole breast radiation (WBI). METHODS: Patients treated from December 2002
      through May 2007 were reviewed. Selection criteria included patients with pTis
      T2N0 disease, <= 3 cm unifocal tumors, and negative margins who underwent breast
      conservation surgery. Local control (LC), cause-specific (CSS) and overall
      survival (OS) were analyzed. RESULTS: 202 patients were identified in the APBI
      cohort and 94 patients in the WBI cohort. Median follow-up for both groups
      exceeded 60 months. LC was 97.0% for the APBI cohort and 96.2% for the WBI cohort
      at 5 years (ns). Classification by 2010 ASTRO APBI consensus statement categories
      did not predict worse outcomes. CONCLUSION: APBI via multicatheter interstitial
      brachytherapy provides similar local failure rates compared to WBI at 5 years for
      properly selected patients. Excellent results were seen despite the high fraction
      of younger patients (< 60 years old) and patients with DCIS.

PMID- 22458889
TI  - Membrane-mediated interactions--a physico-chemical basis for protein sorting.
AB  - Sorting of membrane proteins in eukaryotic cells is a complex yet vital task that
      involves several 10,000 molecular players. Sorting takes place not only along the
      early secretory pathway, i.e., between the endoplasmic reticulum and the Golgi
      apparatus, but also between other organelles, including exchange with the cell's
      plasma membrane. Traditionally, specific binary interactions between proteins
      have been made responsible for most of the protein sorting. A more active role of
      lipids, however, became visible in recent years. Not only do lipids in complex
      membranes show domain formation that may support/suppress sorting events, but
      also collective, membrane-mediated interactions have emerged as a robust physico
      chemical mechanism to drive protein sorting. Here, we will review recent insights
      into these aspects.

PMID- 22458888
TI  - A comparative proteomic study identified LRPPRC and MCM7 as putative actors in
      imatinib mesylate cross-resistance in Lucena cell line.
AB  - BACKGROUND: Although chronic myeloid leukemia (CML) treatment has improved since
      the introduction of imatinib mesylate (IM), cases of resistance have been
      reported. This resistance has been associated with the emergence of multidrug
      resistance (MDR) phenotype, as a BCR-ABL independent mechanism. The classic
      pathway studied in MDR promotion is ATP-binding cassette (ABC) family
      transporters expression, but other mechanisms that drive drug resistance are
      largely unknown. To better understand IM therapy relapse due to the rise of MDR,
      we compared the proteomic profiles of K562 and Lucena (K562/VCR) cells. RESULTS:
      The use of 2-DE coupled with a MS approach resulted in the identification of 36
      differentially expressed proteins. Differential mRNA levels of leucine-rich PPR
      motif-containing (LRPPRC) protein, minichromosome maintenance complex component 7
      (MCM7) and ATP-binding cassette sub-family B (MDR/TAP) member 1 (ABCB1) were
      capable of defining samples from CML patients as responsive or resistant to
      therapy. CONCLUSIONS: Through the data presented in this work, we show the
      relevance of MDR to IM therapy. In addition, our proteomic approach identified
      candidate actors involved in resistance, which could lead to additional
      information on BCR-ABL-independent molecular mechanisms.

PMID- 22458890
TI  - Single cigar-shaped nanopores functionalized with amphoteric amino acid chains:
      experimental and theoretical characterization.
AB  - We present an experimental and theoretical characterization of single cigar
      shaped nanopores with pH-responsive carboxylic acid and lysine chains
      functionalized on the pore surface. The nanopore characterization includes (i)
      optical images of the nanostructure obtained by FESEM; (ii) different chemical
      procedures for the nanopore preparation (etching time and functionalizations; pH
      and electrolyte concentration of the external solution) allowing externally
      tunable nanopore responses monitored by the current-voltage (I-V) curves; and
      (iii) transport simulations obtained with a multilayer nanopore model. We show
      that a single, approximately symmetric nanopore can be operated as a
      reconfigurable diode showing different rectifying behaviors by applying chemical
      and electrical signals. The remarkable characteristics of the new nanopore are
      the sharp response observed in the I-V curves, the improved tunability (with
      respect to previous designs of symmetric nanopores) which is achieved because of
      the direct external access to the nanostructure mouths, and the broad range of
      rectifying properties. The results concern both fundamental concepts useful for
      the understanding of transport processes in biological systems (ion channels) and
      applications relevant for tunable nanopore technology (information processing and
      drug controlled release).

PMID- 22458891
TI  - Retention during processing and bioaccessibility of beta-carotene in high beta
      carotene transgenic cassava root.
AB  - Cassava is a root crop that serves as a primary caloric source for many African
      communities despite its low content of beta-carotene (betaC). Carotenoid content
      of roots from wild type (WT) and three transgenic lines with high betaC were
      compared after cooking and preparation of nonfermented and fermented flours
      according to traditional African methods. The various methods of processing all
      decreased betaC content per gram dry weight regardless of genotype. The greatest
      loss of betaC occurred during preparation of gari (dry fermentation followed by
      roasting) from WT and transgenic lines. The quantities of betaC in cooked
      transgenic cassava root that partitioned into mixed micelles during in vitro
      digestion and transported into Caco-2 cells were significantly greater than those
      for identically processed WT root. These results suggest that transgenic high
      betaC cassava will provide individuals with greater quantities of bioaccessible
      betaC.

PMID- 22458894
TI  - Butterfly needles reduce the incidence of nerve injury during phlebotomy.

PMID- 22458895
TI  - Diagnosis of leishmania.

PMID- 22458896
TI  - "No pay, no play": game over.

PMID- 22458897
TI  - Introduction to continuing special series.

PMID- 22458898
TI  - Genitourinary tumor pathology: introductory comments.

PMID- 22458899
TI  - Selected common diagnostic problems in urologic pathology: perspectives from a
      large consult service in genitourinary pathology.
AB  - CONTEXT: Several common differential diagnoses are encountered in urologic
      pathology, frequently causing patient referrals for a second opinion. OBJECTIVES:
      To review 3 common differential diagnoses encountered in a large consultation
      service in genitourinary pathology, including partial atrophy versus prostatic
      acinar adenocarcinoma, oncocytoma versus chromophobe renal cell carcinoma, and
      urothelial carcinoma in situ versus normal urothelium and reactive atypia. We
      will discuss the detailed, morphologically distinctive features and the
      usefulness of immunohistochemistry. DATA SOURCES: Personal experience and review
      of the current literature. CONCLUSIONS: Careful morphologic assessment and
      awareness of diagnostic pitfalls are fundamental in reaching a definitive
      diagnosis in most cases. Immunohistochemistry is useful but should be used only
      in conjunction with the morphologic impression.

PMID- 22458901
TI  - Renal cell carcinoma with clear cell and papillary features.
AB  - CONTEXT: The diagnosis of primary renal cell carcinomas (RCCs) with both
      papillary architecture and cells with clear cytoplasm can be diagnostically
      challenging for practicing pathologists. The 4 main neoplasms in the differential
      diagnosis are clear cell RCC, papillary RCC, clear cell papillary RCC, and Xp11
      translocation RCC. Accurate diagnosis has both prognostic and therapeutic
      implications. OBJECTIVE: To highlight the helpful cytomorphologic,
      immunohistochemical, and cytogenetic features of each of these entities to enable
      reproducible classification. DATA SOURCES: Published peer-reviewed literature was
      reviewed, accompanied by the authors' personal experiences. CONCLUSIONS: Key
      morphologic clues and a focused immunohistochemical panel, including CK7, alpha
      methylacyl coenzyme A racemase (AMACR), TFE3, cathepsin K, and carbonic anhydrase
      IX (CAIX), now allow most resected RCCs with papillary architecture and clear
      cells to be accurately classified. In other cases, cytogenetic and molecular
      findings can establish the diagnosis. Despite these tools, some RCCs with
      papillary architecture and clear cells do not fit into any of the described
      entities and currently remain unclassified.

PMID- 22458902
TI  - Spectrum of preneoplastic and neoplastic cystic lesions of the kidney.
AB  - CONTEXT: Cystic lesions of the kidney may be accompanied by a range of neoplasms
      with distinct prognoses and future risks of developing additional tumors. In
      addition, some renal tumors, with or without accompanying renal cysts, may show a
      prominent cystic component. In the adult population, neoplasms occurring in a
      background of renal cystic diseases and cystic renal neoplasms often pose
      diagnostic challenges because of their many overlapping features. OBJECTIVE: To
      review the clinicopathologic characteristics of common entities in the spectrum
      of neoplastic and potential preneoplastic cystic lesions encountered in adults,
      with an emphasis on renal cystic diseases associated with tumor development and
      on renal neoplasms with predominantly cystic morphology. DATA SOURCES: The
      relevant English-language literature was reviewed, accompanied by the authors'
      experience at their practicing institution. CONCLUSIONS: The presence of multiple
      renal cysts, both acquired and syndromic, can be associated with a variety of
      renal tumors. The morphology of the cysts and associated tumor types can help
      predict the genetic or acquired basis of the lesions, and particularly in
      specimens with no accompanying pertinent clinical history, such potential
      associations should be suggested in surgical pathology reports.

PMID- 22458903
TI  - Role of immunohistochemistry in diagnosing renal neoplasms: when is it really
      useful?
AB  - CONTEXT: With the refinement of molecular and histologic classifications of renal
      neoplasms and the availability of more-effective molecular targeted therapy for
      specific renal neoplasms, immunohistochemical techniques will play an
      increasingly important role in the diagnosis of renal neoplasm. During the past
      few decades, many markers have been evaluated for their role in the diagnosis,
      prognosis, and prediction of treatment for renal neoplasms. The number of useful
      markers in our routine practice continues to increase. The challenge will be to
      choose among them and to decide in which situations immunohistochemistry will be
      truly useful. OBJECTIVES: To review the diagnostic utility of molecular markers
      for renal neoplasms and common diagnostic scenarios that call for
      immunohistochemistry in routine practice. DATA SOURCES: This review is based on
      published literature and personal experience. CONCLUSIONS: Some of the most
      important and useful markers for the diagnosis of renal neoplasm include
      cytokeratins, vimentin, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific
      cadherin, parvalbumin, claudin-7, claudin-8, alpha-methylacyl coenzyme A
      racemase, CD117, TFE3, thrombomodulin, uroplakin III, p63, CD57, and carbonic
      anhydrase IX. Each marker has its diagnostic role in a specific diagnostic
      setting. The common diagnostic situations that call for immunohistochemical
      staining are differential diagnoses of renal versus nonrenal neoplasms,
      histologic subtyping of renal cell carcinoma, diagnosis of rare primary renal
      neoplasms, diagnosis of renal neoplasms in small core-biopsy specimens, diagnosis
      of possible metastatic renal carcinomas, and less frequently, molecular
      prognostication.

PMID- 22458904
TI  - Intraductal carcinoma of the prostate.
AB  - CONTEXT: Intraductal carcinoma of the prostate (IDC-P) is a distinct
      clinicopathologic entity, characterized by an expansile proliferation of
      secretory cells within prostatic ducts and acini that demonstrate marked
      architectural and cytologic atypia. Intraductal carcinoma of the prostate is
      strongly associated with high-grade and high-volume, invasive prostate cancer and
      a poorer prognosis than cases without IDC-P. OBJECTIVE: To review the historic
      perspectives, pathologic and genetic features, diagnostic criteria and
      differential diagnoses, and the clinical significance of IDC-P. DATA SOURCES:
      Relevant studies indexed in PubMed. CONCLUSIONS: It is critical to recognize IDC
      P, especially in prostate biopsies in which the clinical implications of IDC-P
      are greatest. Morphologic criteria have been proposed to distinguish IDC-P from
      several other lesions with similar histologic appearance such as high-grade
      prostatic intraepithelial neoplasia, invasive cribriform prostate cancer, and
      urothelial carcinoma involving the prostate. Intraductal carcinoma of the
      prostate is an uncommon finding in prostate biopsies, and it is even rarer as an
      isolated finding without concomitant prostate cancer in biopsies. However,
      patients with isolated IDC-P in biopsies are recommended for either definitive
      treatment or immediate repeat biopsy.

PMID- 22458905
TI  - Implications of the International Society of Urological Pathology modified
      Gleason grading system.
AB  - CONTEXT: Histologic grading is the clinically most useful tissue-based predictor
      of prognosis for prostate cancer. Over the years, there has been a gradual shift
      in how the Gleason grading is applied in practice, with a general trend toward
      upgrading. A consensus conference was organized in 2005 by the International
      Society of Urological Pathology (ISUP) for standardizing both the perception of
      histologic patterns and how the grade information is compiled and reported.
      OBJECTIVE: To review the implications of the ISUP modified Gleason grading
      system. DATA SOURCES: Personal experience and review of the current literature.
      CONCLUSIONS: The recommendations regarding pattern interpretation and reporting
      are summarized. The practical consequences of the ISUP modification of the
      Gleason grading are reported. The prognostic importance of the Gleason score, its
      reproducibility, and its preoperative assessment are discussed. Subsequent
      proposals for slight modifications to the ISUP grading system are described.

PMID- 22458907
TI  - Trends in pancreatic pathology practice before and after implementation of
      endoscopic ultrasound-guided fine-needle aspiration: an example of disruptive
      innovation effect?
AB  - CONTEXT: Little has been reported on changes in pancreatic pathology practice
      after implementation of endoscopic ultrasound-guided fine-needle aspiration (EUS
      FNA). OBJECTIVES: We assessed the impact of EUS-FNA on cytologic diagnosis
      replacing histologic diagnosis for pancreatic disease and determined whether it
      fulfills Christensen criteria of a disruptive innovation effect. DESIGN: Pattern
      of utilization during 20 years, diagnostic categories, and diagnostic accuracy of
      pancreatic cytology were compared before and after implementation of EUS-FNA. The
      disruptive effect of cytology relevant to biopsy was assessed by comparing the
      utilization trends and the accuracy of diagnosis over time. RESULTS: The mean
      annual volume (standard deviation) of cytologic specimens increased from 24 (11)
      to 231 (10) after implementation of EUS-FNA, and that of histologic specimens
      increased from 97 (42) to 377 (148). The average percentage of annual cases
      managed by following cytology alone was 19% (10) before versus 51% (8) after
      implementation. The percentage managed by histology alone was 56% before versus
      23% after implementation. Non-endoscopic ultrasound-guided fine-needle aspiration
      cytology decreased from 36% to 1%. Needle biopsies decreased from 7% to 1%, and
      other biopsy types from 29% to 9%. Unsatisfactory (7% versus 1%), atypical (16%
      versus 4%), and suspicious (16% versus 3%) diagnoses were significantly reduced.
      The accuracy of cytologic diagnosis significantly improved: the sensitivity
      (confidence interval) and specificity (confidence interval) for cancer diagnosis
      were 55% (38%-70%) and 78% (58%-89%) before versus 88% (84%-91%) and 96% (93%
      98%) after implementation, respectively. CONCLUSIONS: Endoscopic ultrasound
      guided fine-needle aspiration improved the accuracy of cytologic diagnosis,
      reduced the number of indeterminate diagnoses, and replaced the need for tissue
      biopsy. Given its cost and simplicity as compared with tissue biopsy, this trend
      represents a disruptive innovation effect.

PMID- 22458906
TI  - Difficult differential diagnoses in testicular pathology.
AB  - CONTEXT: Although relatively rare, testicular cancer is the most common solid
      organ malignancy in young men and remains a leading cause of cancer death in this
      population. Different types of testicular tumors are treated differently, with an
      overall very high cure rate with proper management. Pathologists must, therefore,
      be familiar with important diagnostic pitfalls in testicular pathology,
      particularly those that result in different treatments or prognoses. OBJECTIVE:
      To summarize key diagnostic features and useful ancillary tools for the most
      frequently encountered problems in testicular tumor pathology. DATA SOURCES:
      Current texts, PubMed (National Library of Medicine) articles, and archives at
      Indiana University School of Medicine and Beth Israel Deaconess Medical Center
      were all reviewed. CONCLUSIONS: Problematic differential diagnoses include
      seminoma versus nonseminomatous germ cell tumors, germ cell tumors versus non
      germ cell tumors, intratubular germ cell neoplasia versus atypical germ cells
      with maturation arrest, pseudolymphovascular invasion versus real lymphovascular
      invasion in germ cell tumors, and macroscopic Sertoli cell nodules versus Sertoli
      cell tumors. In almost all cases, awareness of the differential diagnostic
      possibilities based on routine light microscopic features permits application of
      either additional, directed observations or immunohistochemical studies that lead
      to an accurate diagnosis.

PMID- 22458908
TI  - Primary cardiac synovial sarcoma.
AB  - Primary cardiac synovial sarcoma is an uncommon malignant neoplasm, with only a
      handful of cases reported in the English literature to date. Synovial sarcomas
      have also been described at other unusual sites, such as the heart,
      pleuropulmonary region, kidney, prostate, liver, mediastinum, retroperitoneum,
      gastrointestinal tract, and peripheral nerve. For synovial sarcomas that arise at
      these unusual locations, definitive diagnosis is challenging and requires use of
      ancillary diagnostic procedures, such as immunohistochemistry, electron
      microscopy, and molecular genetic techniques, for confirmation of diagnosis. The
      nonrandom occurrence of t(X;18) has been found consistently in synovial sarcomas.
      It has also been found as a sole cytogenetic abnormality in some cases,
      suggesting it as a key molecular event in tumor development. This review
      highlights salient features of primary cardiac synovial sarcoma and the
      associated diagnostic challenges.

PMID- 22458900
TI  - Emerging critical role of molecular testing in diagnostic genitourinary
      pathology.
AB  - CONTEXT: The unprecedented advances in cancer genetics and genomics are rapidly
      affecting clinical management and diagnostics in solid tumor oncology. Molecular
      diagnostics is now an integral part of routine clinical management in patients
      with lung, colon, and breast cancer. In sharp contrast, molecular biomarkers have
      been largely excluded from current management algorithms of urologic
      malignancies. OBJECTIVE: To discuss promising candidate biomarkers that may soon
      make their transition to the realm of clinical management of genitourologic
      malignancies. The need for new treatment alternatives that can improve upon the
      modest outcome so far in patients with several types of urologic cancer is
      evident. Well-validated prognostic molecular biomarkers that can help clinicians
      identify patients in need of early aggressive management are lacking. Identifying
      robust predictive biomarkers that will stratify response to emerging targeted
      therapeutics is another crucially needed development. A compiled review of
      salient studies addressing the topic could be helpful in focusing future efforts.
      DATA SOURCES: A PubMed (US National Library of Medicine) search for published
      studies with the following search terms was conducted: molecular , prognostic ,
      targeted therapy , genomics , theranostics and urinary bladder cancer , prostate
      adenocarcinoma , and renal cell carcinoma . Articles with large cohorts and
      multivariate analyses were given preference. CONCLUSIONS: Our recent
      understanding of the complex molecular alterations involved in the development
      and progression of urologic malignancies is yielding novel diagnostic and
      prognostic molecular tools and opening the doors for experimental targeted
      therapies for these prevalent, frequently lethal solid tumors.

PMID- 22458909
TI  - Alcohol prevention in Swedish antenatal care: effectiveness and perceptions of
      the Risk Drinking project counseling model.
AB  - OBJECTIVE: To compare an earlier Swedish antenatal care counseling routine
      concerning alcohol consumption with an expanded model in terms of effectiveness
      in achieving abstinence in pregnancy. A further objective was to assess the
      women's perceptions of the alcohol counseling. DESIGN: Cohort study. SETTING:
      Antenatal care center in a provincial Swedish university town. POPULATION: Women
      who received alcohol counseling; 1533 in cohort 1 (routine counseling) and 1476
      in cohort 2 (expanded model). Approximately 93% of all pregnant women in
      Linkoping are registered at this center. METHODS: Data were collected by means of
      an anonymous questionnaire. Thirteen questions in the questionnaire were analysed
      for this study. MAIN OUTCOME MEASURES: Replies from three questions concerning
      pre-pregnancy drinking and three questions on drinking during pregnancy. RESULTS:
      The response rate was 60% for cohort 1 and 64% for cohort 2. Perceptions of the
      advice from the antenatal care center were generally favorable. Similar
      proportions of women, approximately 6%, in both cohorts drank at least once
      during the pregnancy (after pregnancy recognition). There were four predictors
      for drinking during pregnancy: older age; having previously given birth to a
      child; frequency of pre-pregnancy drinking; and perceiving the message from
      antenatal care as "small amounts of alcohol during pregnancy don't matter."
      CONCLUSIONS: An expanded counseling model implemented in Swedish antenatal care
      did not reduce the proportion of women who continued drinking during pregnancy in
      comparison with a previous counseling model, although the advice provided in the
      new model was perceived more favorably.

PMID- 22458910
TI  - Push-out strength of root fillings with or without thermomechanical compaction.
AB  - AIM: To evaluate the influence of thermomechanical compaction (Tagger's hybrid
      technique - THT) on the push-out strength of several root filling materials to
      root dentine. METHODOLOGY: Root canals of eighty roots in human canines were
      prepared with the ProTaper system and filled with one of the following materials,
      using either lateral compaction (LC) (n = 40) or THT (n = 40): AH Plus/gutta
      percha (GP) (n = 10), Sealer 26/GP (n = 10), Epiphany SE/Resilon (n = 10) and
      Epiphany SE/GP (n = 10). Three 2-mm-thick dentine slices were obtained from each
      third of each root. The root filling in the first slice was subjected to a push
      out test to evaluate the bond strength of the materials to intraradicular
      dentine. Data (in MPa) were analysed using anova and post hoc Tukey's test (P <
      0.05). Failure mode was determined at * 25 magnification. The other two slices
      were prepared for scanning electron microscopy (SEM) to examine the surface of
      the filling materials. RESULTS: Lateral compaction (1.34 +/- 1.14 MPa) was
      associated with a significantly higher bond strength (P < 0.05) than the THT
      (0.97 +/- 0.88 MPa). AH Plus/GP (2.23 +/- 0.83 MPa) and Sealer 26/GP (1.86 +/-
      0.50 MPa) had significantly higher bond strengths than the other materials and
      differed significantly from each other (P < 0.05). There was a significant
      difference (P < 0.05) between the coronal (1.36 +/- 1.15 MPa), middle (1.14 +/-
      1.05 MPa) and apical thirds (0.95 +/- 0.83 MPa). Considering the technique and
      root filling material interaction, AH Plus/GP-LC was associated with the highest
      mean values (2.65 +/- 0.66 MPa) (P < 0.05). Sealer 26/GP-LC (2.10 +/- 0.46 MPa),
      AH Plus/GP-THT (1.81 +/- 0.78 MPa) and Sealer 26/GP-TH (1.63 +/- 0.44 MPa) had
      intermediate values that were not significantly different from each other (P >
      0.05). Epiphany SE was associated with the lowest mean values (3.70 +/- 0.86 MPa)
      (P < 0.05), regardless of the root filling technique and type of solid material
      (cone). Adhesive failures predominated in the specimens filled with Epiphany SE,
      whilst mixed and cohesive failures were more frequent in those filled with AH
      Plus and Sealer 26, regardless of the root filling technique. SEM analysis
      revealed that LC produced a dense and well-compacted filling whilst the use of a
      hybrid thermomechanical technique resulted in the solid material (GP or Resilon)
      intermingled within sealer to form a nonhomogenous mass. CONCLUSION: Lateral
      compaction was associated with higher bond strengths of the materials to
      intraradicular dentine than a hybrid technique using thermomechanical compaction.
      The greatest push-out strengths were obtained when the canals were filled with LC
      of AH Plus and GP cones.

PMID- 22458911
TI  - Effects of incubation temperature and semen pooling on the viability of fresh,
      chilled and freeze-thawed canine semen samples.
AB  - This study assessed the effects of different incubation temperatures on semen
      viability and the influence of pooling on semen longevity. In experiment 1, semen
      samples were collected from five dogs, individually processed (individual semen:
      IS) and then aliquots from each male were pooled (pooled semen: PS). Semen
      samples (IS and PS) were diluted in a Tris-glucose-yolk extender and preserved as
      fresh (37 and 25 degrees C) and chilled semen (4 degrees C). Sperm motility and
      the percentages of sperm abnormalities and acrosome membrane integrity were
      assessed for 24 h. Storage at 25 or 4 degrees C for the first 24 h yielded
      similar semen quality, but incubation at 37 degrees C caused drastic reduction in
      sperm motility from 8 h of incubation onwards. In experiment 2, the semen was
      processed in the same way to that of experiment 1 and then preserved at 25 or 4
      degrees C until semen inactivation. Semen that was incubated at 25 degrees C
      became completely inactive after 3-4 days of storage, while semen that was
      preserved at 4 degrees C presented with more gradually decreased sperm motility
      (mean values of 40-60% for the first 8 days). In addition, the mixing of semen
      was only observed to influence the sperm quality of the samples stored at 4
      degrees C. In experiment 3, semen was collected from five dogs, pooled and frozen
      in liquid nitrogen; after thawing, it was preserved at 37, 25, 15 and 4 degrees
      C, and the sperm quality was defined. The motility of the freeze-thawed semen
      samples decreased quickly in the first 4 h after thawing, regardless of the
      preservation temperature of the thawed semen. This study confirmed that semen
      preserved at 37 degrees C should be used within a maximum of 12 h, while the
      semen stored at 25 degrees C shows acceptable quality for 24 h. Chilled semen
      presented highest most sustainable quality, especially when semen is processed as
      pooled semen.

PMID- 22458912
TI  - Report on emerging technologies for translational bioinformatics: a symposium on
      gene expression profiling for archival tissues.
AB  - BACKGROUND: With over 20 million formalin-fixed, paraffin-embedded (FFPE) tissue
      samples archived each year in the United States alone, archival tissues remain a
      vast and under-utilized resource in the genomic study of cancer. Technologies
      have recently been introduced for whole-transcriptome amplification and
      microarray analysis of degraded mRNA fragments from FFPE samples, and studies of
      these platforms have only recently begun to enter the published literature.
      RESULTS: The Emerging Technologies for Translational Bioinformatics symposium on
      gene expression profiling for archival tissues featured presentations of two
      large-scale FFPE expression profiling studies (each involving over 1,000
      samples), overviews of several smaller studies, and representatives from three
      leading companies in the field (Illumina, Affymetrix, and NuGEN). The meeting
      highlighted challenges in the analysis of expression data from archival tissues
      and strategies being developed to overcome them. In particular, speakers reported
      higher rates of clinical sample failure (from 10% to 70%) than are typical for
      fresh-frozen tissues, as well as more frequent probe failure for individual
      samples. The symposium program is available at http://www.hsph.harvard.edu/ffpe.
      CONCLUSIONS: Multiple solutions now exist for whole-genome expression profiling
      of FFPE tissues, including both microarray- and sequencing-based platforms.
      Several studies have reported their successful application, but substantial
      challenges and risks still exist. Symposium speakers presented novel methodology
      for analysis of FFPE expression data and suggestions for improving data recovery
      and quality assessment in pre-analytical stages. Research presentations
      emphasized the need for careful study design, including the use of pilot studies,
      replication, and randomization of samples among batches, as well as careful
      attention to data quality control. Regardless of any limitations in quantitave
      transcriptomics for FFPE tissues, they are often the only biospecimens available
      for large patient populations with long-term history and clinical follow-up.
      Current challenges can be expected to remain as RNA sequencing matures, and they
      will thus motivate ongoing research efforts into noise reduction and
      identification of robust, translationally relevant biological signals in
      expression data from FFPE tissues.

PMID- 22458913
TI  - Osteopontin and symmetric dimethylarginine plasma levels in solitary functioning
      kidney in children.
AB  - AIM: The present study aimed to examine whether plasma osteopontin (pOPN) and
      symmetric dimethylarginine (pSDMA) are useful biomarkers of renal dysfunction in
      children with solitary functioning kidney (SFK). METHODS: We measured circulating
      pOPN and pSDMA in 51 patients with SFK and no other urinary defects. Patients
      were subdivided into two groups: primary SFK (pSFK) - unilateral renal agenesis
      (URA), and secondary SFK (sSFK) - unilateral nephrectomy. The control group (C)
      contained 21 healthy children, with mean age 9.92 +/- 4.85 years. Immunoenzymatic
      ELISA commercial kits were used to measure pOPN and pSDMA concentrations.
      RESULTS: Plasma osteopontin and pSDMA levels in children with SFK were higher
      than those in healthy participants (p < 0.05). There was no difference in pOPN
      and pSDMA concentrations between patients with pSFK and those with sSFK (p >
      0.05). Receiver operator characteristic analyses performed to define the
      diagnostic efficiency of serum creatinine, pOPN and pSDMA in identifying children
      with C(cr)  < 90 mL/min/1.73 m(2) among all examined children revealed no
      differences between all three AUCs (p > 0.05). CONCLUSION: Increased pOPN and
      pSDMA levels were observed in children with SFK. Both pOPN and pSDMA correlated
      with eGFR; however, the sensitivity and specificity of those markers were not
      better than those of creatinine.

PMID- 22458915
TI  - Bayesian networks and the value of the evidence for the forensic two-trace
      transfer problem.
AB  - Forensic scientists face increasingly complex inference problems for evaluating
      likelihood ratios (LRs) for an appropriate pair of propositions. Up to now,
      scientists and statisticians have derived LR formulae using an algebraic
      approach. However, this approach reaches its limits when addressing cases with an
      increasing number of variables and dependence relationships between these
      variables. In this study, we suggest using a graphical approach, based on the
      construction of Bayesian networks (BNs). We first construct a BN that captures
      the problem, and then deduce the expression for calculating the LR from this
      model to compare it with existing LR formulae. We illustrate this idea by
      applying it to the evaluation of an activity level LR in the context of the two
      trace transfer problem. Our approach allows us to relax assumptions made in
      previous LR developments, produce a new LR formula for the two-trace transfer
      problem and generalize this scenario to n traces.

PMID- 22458914
TI  - Modulation of TTX-sensitive voltage-dependent Na+ channels by beta-bungarotoxin
      in rat cerebellar neurons.
AB  - BACKGROUND: The modulation of voltage-dependent Na+ channels by lipid metabolites
      such as arachidonic acid or eicosanoids plays a role in physiological functions
      as well as in degenerative diseases. So far TTX-resistant channels were found
      mainly to be regulated by lipid metabolites. RESULTS: We investigated the lipid
      dependent modulation of TTX-sensitive (TTX-s) Na+ channels using beta
      bungarotoxin (beta-BuTX, 10 pM), which has an intrinsic phospholipase-A2
      activity, and indomethacin (10 MUM), which blocks cyclooxygenase activity in
      primary cerebellar neurons. To investigate TTX-s Na+ channels, whole-currents
      were measured under K+-free conditions and blocked by 10 nM TTX. The currents
      resulting from calculating the difference of currents measured in the presence
      and the absence of TTX were used for further analysis. Application of
      indomethacin mainly changed the current kinetics but has only minor effects on
      voltage-dependence. In contrast beta-BuTX increased the maximal current amplitude
      and shifted the voltage-dependent activation towards more negative potentials.
      The effects of beta-BuTX were blocked by indomethacin. Analysis of lipid
      metabolites which accumulate by treatment with beta-BuTX using MALDI-TOF MS
      showed an increase of cyclooxygenase reaction products in relation to arachidonic
      acid. CONCLUSIONS: In summary, we conclude that TTX-sensitive Na+ channels can be
      directly modulated by cyclooxygenase reaction products leading to higher activity
      at less depolarized potentials and subsequent higher excitability of neurons.
      Since activation of cyclooxygenase is also involved in pathways leading to
      apoptotic cells death this could play a role in degenerative diseases of the CNS
      and highlights a possible protective effect of cyclooxygenase inhibition.

PMID- 22458916
TI  - Completing the surrogate motherhood process: parental order reporters' attitudes
      towards surrogacy arrangements, role ambiguity and role conflict.
AB  - This study investigated the attitudes of parental order reporters (PORs) towards
      their work with surrogacy arrangements and their experiences of role conflict and
      role ambiguity. A questionnaire was used to assess PORs' perceptions of their
      role in parental order [PO] applications, attitudes towards surrogacy
      arrangements and the legal process and the influence of role ambiguity or
      conflict. Questionnaires were distributed to all PORs employed by the Children
      and Family Court Advisory and Support Service in England. Thirty-three PORs
      participated (response rate 46%) who, on average, had each completed five PO
      applications (range 1-40). Positive attitudes towards surrogacy and the child's
      needs for openness about origins were found. Concerns about the inadequacy of
      preparation and assessment arrangements, overseas arrangements and non-regulation
      of surrogacy agencies were evident. PORs with high-role ambiguity were more
      likely to report less positive attitudes towards the emotional consequence of
      surrogacy on offspring. High scores on role ambiguity and role conflict were
      reflected in less positive attitudes towards the parties' preparation towards
      parenthood. These results have implications for training, policy and practice in
      this area.

PMID- 22458917
TI  - Extended-release tramadol/paracetamol in moderate-to-severe pain: a randomized,
      placebo-controlled study in patients with acute low back pain.
AB  - OBJECTIVE: Combinations of oral analgesics may offer several potential benefits
      compared with an individual agent. The objective of this study was to investigate
      the efficacy and safety of an extended-release, twice-daily fixed combination of
      75 mg tramadol/650 mg paracetamol (DDS-06C) in the treatment of moderate-to
      severe pain, using acute low back pain as a model. RESEARCH DESIGN AND METHODS:
      In this phase III study, 277 patients with moderate-to-severe acute low back pain
      were randomized to 1-2 tablets of DDS-06C or placebo every 10-12 h for 2.5 days
      during the double-blind phase. Following the double-blind phase, patients had the
      option to continue for a 2.5-day open-label phase. CLINICAL TRIAL REGISTRATION:
      Clinicaltrials.gov (Identifier: NCT00643383) MAIN OUTCOME MEASURES: The primary
      end point was the sum of pain intensity differences (SPID) over the 50-h double
      blind phase (SPID50). Secondary end points included total pain relief score over
      the 50-h double-blind phase (TOTPAR50), patient's global impression of
      medication, and SPID over the first 4 h. RESULTS: A statistically significant (p
      = 0.038) greater decrease in pain intensity was observed in the DDS-06C group
      (median SPID50: -6.0) versus placebo (median SPID50: -4.0). Greater pain relief
      was also observed in patients randomized to DDS-06C: the median TOTPAR50 was 13.0
      for the DDS-06C group and 11.0 for placebo (p = 0.026). DDS-06C demonstrated
      statistically significant superior efficacy compared with placebo for the
      majority of the other secondary end points. Overall, 38% of patients treated with
      DDS-06C experienced at least one adverse event; the intensity was mild-to
      moderate in 81% of cases. The most commonly reported adverse events (>5% of
      patients receiving DDS-06C) were nausea, dizziness, vomiting, and somnolence.
      CONCLUSIONS: Using acute low back pain, a model with a high degree of
      heterogeneity and intrinsic variability, DDS-06C was superior to placebo on
      measures of pain intensity and relief, and was well-tolerated.

PMID- 22458918
TI  - Fixed-combination brimonidine-timolol versus latanoprost in glaucoma and ocular
      hypertension: a 12-week, randomized, comparison study.
AB  - OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering efficacy and
      safety of fixed-combination brimonidine 0.2%-timolol 0.5% compared with
      latanoprost 0.005% in patients with glaucoma or ocular hypertension. RESEARCH
      DESIGN AND METHODS: This was a prospective, randomized, multicenter, investigator
      masked clinical trial. After washout of any previous IOP-lowering medications,
      patients with IOP of 24 mmHg or higher were randomized to twice-daily fixed
      combination brimonidine 0.2%-timolol 0.5% (n = 73) or once-daily latanoprost
      0.005% (n = 75, dosed in the evening, with vehicle control in the morning to
      maintain masking) for 12 weeks. IOP was measured at 8 a.m. (before dosing), 10
      a.m., and 3 p.m. at baseline, week 6, and week 12. CLINICAL TRIAL REGISTRATION:
      The trial is registered with the identifier 00811564 at
      http://www.clinicaltrials.gov . MAIN OUTCOME MEASURES: The primary efficacy
      endpoint was diurnal IOP (averaged over 8 a.m., 10 a.m., and 3 p.m.) at week 12.
      Safety measures included biomicroscopy. RESULTS: There was no statistically
      significant difference between the treatment groups in mean diurnal IOP at
      baseline (p = 0.118). At week 12, the mean (SD) diurnal IOP was 17.8 (2.9) mmHg
      with brimonidine-timolol and 17.9 (3.9) mmHg with latanoprost (p = 0.794). The
      percentage of patients achieving at least a 20% decrease from baseline diurnal
      IOP at week 12 was 87.7% in the brimonidine-timolol group and 77.3% in the
      latanoprost group (p = 0.131). Measured biomicroscopic changes from baseline to
      week 12 were infrequent in both groups. CONCLUSIONS: Fixed-combination
      brimonidine-timolol was as effective as latanoprost in reducing IOP in patients
      with glaucoma or ocular hypertension. Both treatments demonstrated favorable
      ocular tolerability. The duration of the study was 12 weeks, and additional
      studies will be needed to compare the efficacy and safety of fixed-combination
      brimonidine-timolol and latanoprost during long-term treatment.

PMID- 22458919
TI  - Skin reactions in a phase 3 study of a testosterone topical solution applied to
      the axilla in hypogonadal men.
AB  - OBJECTIVE: Axiron (testosterone topical solution 2%) is an approved topical
      testosterone replacement therapy applied to the axilla. The axilla is a novel
      application site for testosterone replacement therapy, with differences in skin
      structure and exposure that could impact the type and/or severity of skin
      reactions observed with testosterone topical solution 2%. We therefore present a
      detailed description of data from a pivotal clinical trial regarding the
      incidence, time of onset, duration, and severity of patient-reported skin
      reactions as well as visual assessments made by investigators and rated using
      Draize scoring. *Axiron is a trademark of Eli Lilly and Company, Indianapolis,
      IN, USA. METHODS: Data were analyzed from a multinational, open-label, clinical
      study in which a 2% testosterone topical solution was applied to the axilla in
      hypogonadal men. The primary study was for 120 days (N = 155) with a 60-day
      extension that evaluated skin safety (N = 71). At each visit investigators asked
      patients about adverse skin reactions (including those occurring between study
      visits); visually assessed the application site; and graded observed instances of
      erythema or edema using Draize scoring (rated from 0 to 4). RESULTS: Application
      site irritation following study drug application was the most commonly reported
      event (n = 12 patients) and was generally mild (n = 11; moderate, n = 1) in
      severity. Application-site irritation did not increase in severity over time and
      led to only one discontinuation. Erythema was the second most common patient
      reported skin reaction (n = 10 patients) and was also generally mild (n = 9;
      moderate, n = 1). Draize scoring rated all directly observed cases of erythema as
      grade 1 (very slight, 6 patients) or grade 2 (well-defined, two patients), and
      identified two instances of erythema not reported by patients. Erythema was
      typically transient, and in most cases resolved without interruption of therapy.
      Three cases of edema were reported by patients, and two of these were also
      identified by visual inspection; all cases of edema occurred in conjunction with
      erythema. Two cases of acne (facial, shoulders) and one of folliculitis (scalp)
      were also reported. CONCLUSIONS: Skin reactions were observed in a minority of
      patients, were mild or at most moderate in severity, and seldom led to
      discontinuation.

PMID- 22458921
TI  - Blood-borne viruses in the haemodialysis-dependent population attending Top End
      Northern Territory facilities 2000-2009.
AB  - AIM:   To describe the incidence and prevalence of blood-borne viruses (BBV)
      including: hepatitis B virus (HBV), hepatitis C virus (HCV), human
      immunodeficiency virus (HIV) and human T-cell leukaemia virus type-1 (HTLV) in
      the haemodialysis-dependent population of the Top End of the Northern Territory
      (TENT). METHODS:   We retrospectively reviewed the serology of BBV in a
      longitudinal fashion in the haemodialysis-dependent population treated in the
      TENT of Australia from 2000 to 2009 inclusive. HBV, HCV, HIV and HTLV serology on
      commencement of dialysis and at exit or January 2010, whichever was earlier, as
      well as demographic details were collected. Patients with a change in serological
      status had all serology reviewed. RESULTS:   Four-hundred and forty patients were
      included in the analysis. Of these, 84.3% were Indigenous and 55.4% female, with
      a median age of 50 (IQR 43-59) years at the commencement of haemodialysis.
      Evidence of past HBV infection was documented in 42.7% and 8.9% were hepatitis B
      surface antigen-positive. Positive serology for HTLV was documented in 2.2%, 1.6%
      were hepatitis C antibody-positive and no individual was HIV-positive. Three
      patients had a definite change in their HBV serology over time; this equates to
      an absolute seroconversion risk of 0.1 per 100 person years or 0.0006 per
      dialysis episode. CONCLUSIONS:   In this cohort, there was a high rate of past
      and current hepatitis B infection but low rates of seroconversion while on
      haemodialysis.

PMID- 22458922
TI  - Comparison of trace element emissions from thermal treatments of heavy metal
      hyperaccumulators.
AB  - Phytoextraction has become one of the most promising remediation techniques for
      heavy metal (HM) contaminated soils. However, the technique invariably produces
      large amounts of HM-enriched hyperaccumulators, which need further safe disposal.
      In this study, two different thermal treatment methods are investigated as
      potential options for evaporative separation of HMs from the residues. A
      horizontal tube furnace and a vertical entrained flow tube furnace were used for
      testing the disposal of grounded hyperaccumulators. The release characteristics
      of HMs (Cd, Cu, Pb, and Zn) into flue gas and residues were investigated for
      thermal treatment of the Cd and Zn hyperaccumulators Sedum plumbizincicola and
      Sedum alfredii. In a horizontal tube furnace, incineration favors the
      volatilization of Cu and Cd in contrast to pyrolysis. The percentages of HMs in
      residues after incineration are lower than those after pyrolysis, especially for
      Cd, Pb, and Zn. However, in an entrained flow tube furnace, Zn content in flue
      gas increases with increasing temperature, but Cu and Cd contents are fluctuated.
      In addition, a higher incineration temperature enhances the Cu content in
      residues.

PMID- 22458920
TI  - Sindbis virus induces the production of a novel class of endogenous siRNAs in
      Aedes aegypti mosquitoes.
AB  - Small RNA regulatory pathways are used to control the activity of transposons,
      regulate gene expression and resist infecting viruses. We examined the biogenesis
      of mRNA-derived endogenous short-interfering RNAs (endo-siRNAs) in the disease
      vector mosquito Aedes aegypti. Under standard conditions, mRNA-derived endo
      siRNAs were produced from the bidirectional transcription of tail-tail
      overlapping gene pairs. Upon infection with the alphavirus, Sindbis virus (SINV),
      another class of mRNA-derived endo-siRNAs was observed. Genes producing SINV
      induced endo-siRNAs were not enriched for overlapping partners or nearby genes,
      but were enriched for transcripts with long 3' untranslated regions. Endo-siRNAs
      from this class derived uniformly from the entire length of the target
      transcript, and were found to regulate the transcript levels of the genes from
      which they were derived. Strand-specific quantitative PCR experiments
      demonstrated that antisense strands of targeted mRNA genes were produced to
      exonic, but not intronic regions. Finally, small RNAs mapped to both sense and
      antisense strands of exon-exon junctions, suggesting double-stranded RNA
      precursors to SINV-induced endo-siRNAs may be synthesized from mature mRNA
      templates. These results suggest additional complexity in small RNA pathways and
      gene regulation in the presence of an infecting virus in disease vector
      mosquitoes.

PMID- 22458923
TI  - The group medical appointment (GMA) in haemophilia and von Willebrand's disease:
      a new development in outpatient paediatric care.
AB  - The Group Medical Appointment (GMA) is a novel consultation form in which
      patients undergo individual consultations in each other's presence. To compare
      participants' experiences with GMA and Individual Medical Appointments (IMA), the
      usual standard of care, our team recently implemented the GMA for children aged 0
      18 years with haemophilia or von Willebrand's disease. Participants' experiences
      with GMA were measured using a standardized QUOTE-questionnaire. Of 100 addressed
      families, 53 participated in GMA. Of these 53 families, 38 parents (72%) and 14
      adolescents (82%) filled in the questionnaire about the GMA. Patients not on
      prophylaxis were defined as less experienced and patients on prophylaxis, as
      experienced. Although parents were satisfied with both GMA and IMA (median score
      8.0 vs. 9.0 of 10), a significant difference was demonstrated between less
      experienced and experienced parents. After GMA, less experienced parents were
      significantly more satisfied (median score 8.0 vs. 5.0; P-value 0.006), felt more
      social support (82% vs. 30%; P-value 0.005) and reported additional learning
      effects with regard to disease and treatment (64% vs. 0%; P-value <0.001) than
      experienced parents. None of the less experienced parents reported privacy
      problems during GMA compared with 40% of experienced parents. In adolescents an
      identical trend was reported. Sixty-six per cent of parents would join a GMA in
      the future and 87% would recommend a GMA to others. The GMA is a valuable
      addition in haemophilia and von Willebrand care, especially for less experienced
      patients. It leads to improved satisfaction, social support and improved
      information.

PMID- 22458924
TI  - Effect of methoxychlor on Ca(2+) movement and viability in MDCK renal tubular
      cells.
AB  - The effect of the insecticide methoxychlor on the physiology of renal tubular
      cells is unknown. This study aimed to explore the effect of methoxychlor on
      cytosolic Ca(2+) concentrations ([Ca(2+) ](i) ) in MDCK renal tubular cells using
      the Ca(2+) -sensitive fluorescent dye fura-2. Methoxychlor at 5-20 MUM increased
      [Ca(2+) ](i) in a concentration-dependent manner. The signal was reduced by 80%
      by removing extracellular Ca(2+) . Methoxychlor-induced Ca(2+) entry was not
      affected by nifedipine and SK&F96365 but was inhibited by econazole and protein
      kinase C modulators. In Ca(2+) -free medium, treatment with the endoplasmic
      reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone
      (BHQ) partly inhibited methoxychlor-induced [Ca(2+) ](i) rise. Incubation with
      methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca(2+) ](i) rise.
      Inhibition of phospholipase C with U73122 nearly abolished methoxychlor-induced
      [Ca(2+) ](i) rise. At 5-15 MUM, methoxychlor slightly increased cell viability,
      whereas at 20 MUM, it decreased viability. The cytotoxic effect of methoxychlor
      was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane
      N,N,N,N-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that 10 MUM
      methoxychlor inhibited apoptosis, while 20 MUM methoxychlor enhanced apoptosis.
      Methoxychlor (10 and 20 MUM) increased the production of reactive oxygen species.
      Together, in renal tubular cells, methoxychlor induced [Ca(2+) ](i) rise by
      inducing phospholipase C-dependent Ca(2+) release from multiple stores and Ca(2+)
      entry via protein kinase C- and econazole-sensitive channels. Methoxychlor
      slightly enhanced or inhibited cell viability in a concentration-dependent,
      Ca(2+) -independent manner. Methoxychlor induced cell death that may involve
      apoptosis via mitochondrial pathways.

PMID- 22458926
TI  - Primary cutaneous anaplastic large cell lymphoma simulating an aggressive
      angiocentric T-cell lymphoma.

PMID- 22458927
TI  - Thromboprophylaxis in spinal surgery: a survey.
AB  - BACKGROUND: Venous Thromboembolism (VTE) is the most common complication
      following major joint surgery. While attention has been focused upon the
      incidence of thromboembolic disease following total hip or knee arthroplasty or
      emergency surgery for hip fracture, there exists a gap in the medical literature
      examining the incidence of VTE in spinal surgery. Evidence suggests that the
      prevalence of DVT after spinal surgery is higher than generally recognized but
      with a shortage of epidemiological data, guidelines for optimal prophylaxis are
      limited. This survey, of individuals attending the 2009 British Association of
      Spinal Surgeons Annual Meeting, sought to examine prevailing trends in VTE
      thromboprophylaxis in spinal surgery, adherence to guideline outlined by the
      National Institute for Health and Clinical Excellence (NICE) and to compare
      selections made by orthopaedic and neurosurgeons. METHODS: We developed a
      questionnaire with eight clinical scenarios. Participants were asked to supply
      details on their specialty and to select which method(s) of thromboprophylaxis
      they would employ for each scenario. Chi squared analysis was used for
      statistical comparison of the questionnaire responses. RESULTS: 73% of
      neurosurgical respondents' and 31% of orthopaedic surgeons employed low molecular
      weight heparin (p < 0.001). Neurosurgeons also selected anti-embolism stockings
      more frequently (79% v 50%) while orthopaedic surgeons preferred mechanical
      prophylaxis (26% v 9%). There was no significant difference between trauma and
      non-trauma scenarios (p = 0.05). CONCLUSION: There is no clear consensus in
      thromboprophylaxis in spinal surgery. There was a significant difference in
      selections across surgical disciplines with neurosurgeons more closely adhering
      to national guidelines. Further research examining the epidemiology of venous
      thromboembolism in spinal surgery and the risks-benefit relationship of
      thromboprophylaxis is warranted.

PMID- 22458928
TI  - Maintaining participation and momentum in longitudinal research involving high
      risk families.
AB  - PURPOSE: The purpose of the current study was to identify and describe strategies
      available to optimize retention of a high-risk research cohort and assist in the
      recovery of study participants following participant dropout. DESIGN AND METHODS:
      The Maternal Lifestyle Study (MLS), which investigated the effects of prenatal
      substance exposure (cocaine or opiates) on child outcome, is a prospective
      longitudinal follow-up study that extended from birth through 15 years of age.
      Retention strategies to maximize participation and factors that might negatively
      impact compliance were examined over the course of five follow-up phases.
      FINDINGS: At the conclusion of the 15-year visits, MLS had successfully
      maintained compliance at 76%. Retention rates did not differ by exposure group.
      CONCLUSIONS: Maintaining ongoing participation of enrolled study subjects is a
      critical element of any successful longitudinal study. Strategies that can be
      used to reengage and maintain participants in longitudinal research include
      persistence, flexibility with scheduling, home visits, long-distance trips,
      increased incentives, and development of a computerized tracking system.
      Establishing rapport with families and ensuring confidentiality contributed to
      overall participant retention. The use of multiple tracking techniques is
      essential. CLINICAL RELEVANCE: Researchers are challenged to maintain
      participants in longitudinal studies to ensure the integrity of their research.

PMID- 22458930
TI  - Ion selectivity of crown ethers investigated by UV and IR spectroscopy in a cold
      ion trap.
AB  - Electronic and vibrational spectra of benzo-15-crown-5 (B15C5) and benzo-18-crown
      6 (B18C6) complexes with alkali metal ions, M(+)*B15C5 and M(+)*B18C6 (M = Li,
      Na, K, Rb, and Cs), are measured using UV photodissociation (UVPD) and IR-UV
      double resonance spectroscopy in a cold, 22-pole ion trap. We determine the
      structure of conformers with the aid of density functional theory calculations.
      In the Na(+)*B15C5 and K(+)*B18C6 complexes, the crown ethers open the most and
      hold the metal ions at the center of the ether ring, demonstrating an optimum
      matching in size between the cavity of the crown ethers and the metal ions. For
      smaller ions, the crown ethers deform the ether ring to decrease the distance and
      increase the interaction between the metal ions and oxygen atoms; the metal ions
      are completely surrounded by the ether ring. In the case of larger ions, the
      metal ions are too large to enter the crown cavity and are positioned on it,
      leaving one of its sides open for further solvation. Thermochemistry data
      calculated on the basis of the stable conformers of the complexes suggest that
      the ion selectivity of crown ethers is controlled primarily by the enthalpy
      change for the complex formation in solution, which depends strongly on the
      complex structure.

PMID- 22458929
TI  - Expression TGM2 and BNIP3 have prognostic significance in laryngeal cancer
      patients receiving surgery and postoperative radiotherapy: a retrospective study.
AB  - BACKGROUND: This study was designed to determine the pattern and correlation
      between expression of the HIF-1alpha transcriptional targets TGM2 and BNIP3 in
      laryngeal cancer, and investigate the association of BNIP3 and TGM2 with clinical
      outcome in laryngeal squamous cell carcinoma (SCC) patients receiving
      postoperative radiotherapy. METHODS: Immunostaining with antibodies specific to
      BNIP3 and TGM2 was performed in formalin-fixed, paraffin-embedded specimens from
      148 laryngeal SCC patients. BNIP3 and TGM2 expression was scored as high or low,
      based on the number of tumor cells stained and the staining intensity. All
      patients received postoperative radiotherapy. Patient follow up and
      clinicopathological data were compared using the Chi-squared test, univariate and
      multivariate analyses, and survival curves were generated using the Kaplan-Meier
      method and log-rank test. RESULTS: The 3, 5 and 10-year overall survival rates
      (OS) for all patients were 77.7%, 71.6%, 56.4%, respectively. Primary tumor site,
      T stage, overall stage, lymph-node metastasis, BNIP3 expression and TGM2
      expression were significant prognostic factors for OS in univariate analysis.
      Negative cervical lymph nodes, high BNIP3 expression and low TGM2 expression were
      independent prognostic factors of improved OS in multivariate analysis. BNIP3
      expression correlates with TGM2 expression in laryngeal SCC (P = 0.012).
      CONCLUSIONS: This study indicates that lymph-node metastasis, BNIP3 expression
      and TGM2 expression are independent prognostic factors in laryngeal SCC patients
      receiving postoperative radiotherapy. Further studies are required to investigate
      how BNIP3 and/or TGM2 influence the prognosis of laryngeal SCC patients treated
      with postoperative radiotherapy, and to determine how TGM2 and BNIP3 expression
      are regulated.

PMID- 22458931
TI  - Platelet function in health and disease: from molecular mechanisms, redox
      considerations to novel therapeutic opportunities.
AB  - Increased oxidative stress appears to be of fundamental importance in the
      pathogenesis and development of several disease processes. Indeed, it is well
      known that reactive oxygen species (ROS) exert critical regulatory functions
      within the vascular wall, and it is, therefore, plausible that platelets
      represent a relevant target for their action. Platelet activation cascade
      (including receptor-mediated tethering to the endothelium, rolling, firm
      adhesion, aggregation, and thrombus formation) is tightly regulated. In addition
      to already well-defined platelet regulatory factors, ROS may participate in the
      regulation of platelet activation. It is already established that enhanced ROS
      release from the vascular wall can indirectly affect platelet activity by
      scavenging nitric oxide (NO), thereby decreasing the antiplatelet properties of
      endothelium. On the other hand, recent data suggest that platelets themselves
      generate ROS, which may evoke pro-thrombotic responses, triggering many
      biological processes participating in atherosclerosis initiation, progression,
      and complication. That oxidative stress may alter platelet function is
      conceivable when considering that antioxidants play a role in the prevention of
      cardiovascular disease, although the precise mechanism accounting for changes
      attributable to antioxidants in atherosclerosis remains unknown. It is possible
      that the effects of antioxidants may be a consequence of their enhancing or
      promoting the antiplatelet effects of NO derived from both endothelial cells and
      platelets. This review focuses on current knowledge regarding ROS-dependent
      regulation of platelet function in health and disease, and summarizes in vitro
      and in vivo evidence for their physiological and potential therapeutic relevance.

PMID- 22458932
TI  - Antioxidant enzyme activity and mRNA expression in reproductive tract of adult
      male European Bison (Bison bonasus, Linnaeus 1758).
AB  - Antioxidants in the male reproductive tract are the main defence factors against
      oxidative stress caused by reactive oxygen species production, which compromises
      sperm function and male fertility. This study was designed to determine the
      activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPx), in the testicular and epididymidal
      tissues of adult male European bison (Bison bonasus). The reproductive tract
      tissues were subjected to real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis to quantify mRNA expression levels of five antioxidant
      enzymes: copper/zinc SOD (Cu/Zn SOD), secretory extracellular SOD (Ec-SOD), CAT,
      phospholipid hydroperoxide glutathione peroxidase (PHGPx) and GPx5. The corpus
      and cauda epididymidal tissues displayed greater (p < 0.05) SOD activity compared
      with the testicular tissue. It was found that CAT activity was lowest (p < 0.05)
      in the cauda epididymidis, whereas negligible GPx activity was detected in the
      reproductive tract tissues. There were no detectable differences in the mRNA
      expression level of Cu/Zn SOD among the different reproductive tract tissues.
      Small amounts of Ec-SOD mRNA were found in the reproductive tract, particularly
      in the epididymides. The caput and cauda epididymides exhibited greater (p <
      0.05) level of CAT mRNA expression, whereas PHGPx mRNA was more (p < 0.05)
      expressed in the testis. Furthermore, extremely large amounts of GPx5 mRNA were
      detected in the caput epididymidal tissue compared with other tissues of the
      reproductive tract. It can be suggested that the activity of the antioxidant
      enzymes and the relative gene expression of the enzymes confirm the presence of
      tissue-specific antioxidant defence systems in the bison reproductive tract,
      which are required for spermatogenesis, epididymal maturation and storage of
      spermatozoa.

PMID- 22458933
TI  - Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1
      and BRLF1 in tumors of epithelial, NK- and B-cell origins.
AB  - BACKGROUND: Epstein-Barr virus (EBV) establishes its latency in EBV-associated
      malignancies, accompanied by occasionally reactivated lytic cycle. Promoter CpG
      methylation of EBV genome plays an essential role in maintaining viral latency.
      Two immediate-early (IE) genes, BZLF1 and BRLF1, induce the switch from latent to
      lytic infection. Studies of methylation-dependent binding of BZLF1 and BRLF1 to
      EBV promoters have been well reported, but little is known about the methylation
      status of BZLF1 and BRLF1 promoters (Zp and Rp) in tumor samples. METHODS: We
      evaluated the methylation profiles of Zp and Rp by methylation-specific PCR (MSP)
      and bisulfite genomic sequencing (BGS), as well as BZLF1 and BRLF1 expression by
      semiquantitative reverse transcription (RT)-PCR in tumors of epithelial, NK- and
      B-cell origins. RESULTS: We found that both Zp and Rp were hypermethylated in all
      studied EBV-positive cell lines and tumors of lymphoid (B- or NK cell) or
      epithelial origin, while unmethylated Zp and Rp alleles were detected in cell
      lines expressing BZLF1 and BRLF1. Following azacytidine treatment or combined
      with trichostatin A (TSA), the expression of BZLF1 and BRLF1 was restored along
      with concomitant promoter demethylation, which subsequently induced the
      reactivation of early lytic gene BHRF1 and late lytic gene BLLF1. CONCLUSIONS:
      Hypermethylation of Zp and Rp mediates the frequent silencing of BZLF1 and BRLF1
      in EBV-associated tumors, which could be reactivated by demethylation agent and
      ultimately initiated the EBV lytic cascade.

PMID- 22458934
TI  - Atrioventricular block of intraoperative device closure perimembranous
      ventricular septal defects; a serious complication.
AB  - BACKGROUND: Atrioventricular block (AVB) is a well-reported complication after
      closure of perimembranous ventricular septal defects (VSDs). To report the
      occurrence of AVB either during or following closure of perimembranous VSDs using
      a novel "hybrid" method involving a minimal inferior median incision and of
      intraoperative device closure of the perimembranous VSDs. METHODS: Between
      January 2009 and January 2011, patients diagnosed with perimembranous VSDs
      eligible for intraoperative device closure with a domestic occluder were
      identified. All patients were assessed by real-time transesophageal
      echocardiography (TEE) and electrocardiography. RESULTS: Of the 97 included
      patients, 94 were successfully occluded using this approach. Complete AVB
      occurred in only one case and one case of Mobitz type II AVB was diagnosed
      intraoperatively. In both patients, the procedure was aborted and the AVBs
      quickly resolved. Glucocorticosteroids were administered to another two patients
      who developed Mobitz type II AVB intraoperatively. Those two patients converted
      to Mobitz type I AVB 3 days and 5 days postsurgically. During the follow-up
      period (range, 6-24 months), one patient developed complete AVB 1 week following
      device insertion. Surgical device removal was followed by a rapid and complete
      recovery of atrioventricular conduction. CONCLUSIONS: Intraoperative device
      closure of perimembranous VSDs with a domestic occluder resulted in excellent
      closure rates; however, AVB is a serious complication that can occur either
      during or any time after device closure of perimembranous VSDs. The technique
      described herein may reduce the incidence of perioperative AVB complications.
      Surgeons are encouraged to closely monitor all patients postsurgically to ensure
      AVB does not occur in their patients. Additional long-term data to better
      identify the prevalence and risk factors for AVB in treated patients are needed.

PMID- 22458935
TI  - Health history after intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVE: To establish whether intrahepatic cholestasis of pregnancy (ICP) is
      associated with other diseases during a woman's lifetime. DESIGN: Prospective
      controlled cohort study. SETTING: University Hospital in Finland. POPULATION: A
      total of 575 women with ICP and 1374 control women, all having delivered in 1969
      1988. Questionnaires were sent to 544 ICP patients and 1235 control women.
      Responses were received from 1178 (66.4%). METHODS: Questionnaire survey in
      autumn 2010. MAIN OUTCOME MEASURES: Perceived health, symptoms and complaints,
      diseases diagnosed by a doctor and use of medicines. RESULTS: No statistically
      significant differences were detected in perceived health. Differences in recent
      symptoms and complaints were small. Diagnoses made by a doctor showed higher
      frequencies in the ICP group than in control women for other hepatobiliary
      diseases, breast cancer and hypothyreosis. Diagnosed hypertension and high
      cholesterol requiring medication as well as cardiac arrhythmia were less frequent
      in the ICP group. Women in this group used antacid medicines more often than
      control women. CONCLUSIONS: There were few differences between the ICP patients
      and control women except for a higher frequency of later hepatobiliary disease,
      breast cancer and hypothyreosis. Women with a history of ICP should be screened
      for hypothyreosis more readily than those without. The higher frequency of breast
      cancer warrants further research.

PMID- 22458936
TI  - Sedation with intranasal midazolam of Angolan children undergoing invasive
      procedures.
AB  - AIM: Ambulatory surgery is a daily requirement in poor countries, and limited
      means and insufficient trained staff lead to the lack of attention to the
      patient's pain. Midazolam is a rapid-onset, short-acting benzodiazepine which is
      used safely to reduce pain in children. We evaluated the practicability of
      intranasal midazolam sedation in a suburban hospital in Luanda (Angola), during
      the surgical procedures. METHODS: Intranasal midazolam solution was administered
      at a dose of 0.5 mg/kg. Using the Ramsay's reactivity score, we gave a score to
      four different types of children's behaviour: moaning, shouting, crying and
      struggling, and the surgeon evaluated the ease of completing the surgical
      procedure using scores from 0 (very easy) to 3 (managing with difficulty).
      RESULTS: Eighty children (median age, 3 years) were recruited, and 140 surgical
      procedures were performed. Fifty-two children were treated with midazolam during
      85 procedures, and 28 children were not treated during 55 procedures. We found a
      significant difference between the two groups on the shouting, crying and
      struggling parameters (p < 0.001). The mean score of the ease of completing the
      procedures was significantly different among the two groups (p < 0.0001).
      CONCLUSION: These results provide a model of procedural sedation in ambulatory
      surgical procedures in poor countries, thus abolishing pain and making the
      surgeon's job easier.

PMID- 22458938
TI  - Enrichment of extruded snack products with coproducts from chestnut mushroom
      (Agrocybe aegerita) production: interactions between dietary fiber,
      physicochemical characteristics, and glycemic load.
AB  - Mushrooms are a common vegetable product that have also been linked to
      pharmaceutical and medicinal uses. However, the production of the fruiting bodies
      of mushrooms results in a large quantity of food waste in the form of spent
      compost. Hyphae and the base of fruit bodies from  Agrocybe aegerita  were
      retrieved from spent mushroom compost and refined as a freeze-dried powder. This
      fiber-rich ingredient was used in the manufacture of ready-to-eat extruded cereal
      snack products. Inclusions rates were 0, 5, 10, and 15% w/w replacement levels
      for wheat flour from a control recipe. Inclusion of mushroom coproduct material
      (MCM) was significantly correlated to increased product expansion (r = 0.848) and
      density (r = 0.949) but negatively correlated to water absorption index (WAI; r =
      -0.928) and water solubility index (WSI; r = -0.729). Fiber content could not be
      correlated to differences in pasting properties of extruded snacks even though
      snack products with MCM showed significantly lower final viscosity values
      compared to the control. The potential glycemic response of foods was
      significantly lowered by including MCM (p < 0.05) with a negative correlation
      between fiber content and overall AUC following a standardized in vitro digestion
      method (r = -0.910). Starch content, WAI, and WSI were positively correlated to
      AUC of extruded snacks (r = 0.916, 0.851, and 0.878. respectively). The results
      illustrate a reduction in the potential glycemic response from including 5% (w/w)
      of MCM in extruded snacks exceeds 20%. Thus, the incorporation of MCM in ready-to
      eat snack foods may be of considerable interest to the food industry in trying to
      regulate the glycemic response of foods.

PMID- 22458937
TI  - Cardiac myosin binding protein C and its phosphorylation regulate multiple steps
      in the cross-bridge cycle of muscle contraction.
AB  - Cardiac myosin binding protein C (c-MyBPC) is a thick filament protein that is
      expressed in cardiac sarcomeres and is known to interact with myosin and actin.
      While both structural and regulatory roles have been proposed for c-MyBPC, its
      true function is unclear; however, phosphorylation has been shown to be
      important. In this study, we investigate the effect of c-MyBPC and its
      phosphorylation on two key steps of the cross-bridge cycle using fast reaction
      kinetics. We show that unphosphorylated c-MyBPC complexed with myosin in 1:1 and
      3:1 myosin:c-MyBPC stoichiometries regulates the binding of myosin to actin
      (K(D)) cooperatively (Hill coefficient, h) (K(D) = 16.44 +/- 0.33 MUM, and h =
      9.24 +/- 1.34; K(D) = 11.48 +/- 0.75 MUM, and h = 3.54 +/- 0.67) and
      significantly decelerates the ATP-induced dissociation of myosin from actin
      (K(1)k(+2) values of 0.12 +/- 0.01 and 0.22 +/- 0.01 M(-1) s(-1), respectively,
      compared with a value of 0.42 +/- 0.01 M(-1) s(-1) for myosin alone).
      Phosphorylation of c-MyBPC abolished the regulation of the association phase
      (K(1)k(+2) values of 0.32 +/- 0.02 and 0.33 +/- 0.01 M(-1) s(-1) at 1:1 and 3:1
      myosin:c-MyBPC ratios, respectively) and also accelerated the dissociation of
      myosin from actin (K(1)k(+2) values of 0.23 +/- 0.01 and 0.29 +/- 0.01 M(-1) s(
      1) at a 1:1 and 3:1 myosin:c-MyBPC ratios, respectively) relative to the
      dissociation of myosin from actin in the presence of unphosphorylated c-MyBPC.
      These results indicate a direct effect of c-MyBPC on cross-bridge kinetics that
      is independent of the thin filament that together with its phosphorylation
      provides a mechanism for fine-tuning cross-bridge behavior to match the
      contractile requirements of the heart.

PMID- 22458939
TI  - A randomised, placebo-controlled, dose-finding study of AZD9668, an oral
      inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary
      disease treated with tiotropium.
AB  - AZD9668 is a fully reversible, selective, oral inhibitor of neutrophil elastase,
      a protease implicated in chronic obstructive pulmonary disease (COPD). Efficacy,
      safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with
      placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb
      trial (NCT00949975: approved by an Investigational Review Board), in patients
      with symptomatic COPD receiving maintenance tiotropium. The primary endpoint was
      pre-bronchodilator forced expiratory volume in 1 second (FEV1). Secondary
      endpoints included forced vital capacity and inspiratory capacity, peak
      expiratory flow, Breathlessness, Cough and Sputum Scale score, exercise capacity,
      quality of life (QoL), exacerbation assessments, safety and pharmacokinetics.
      Exploratory endpoints included inflammatory and tissue degradation biomarkers. A
      total of 838 patients were randomised to AZD9668 5 mg bid (212 patients), 20 mg
      bid (206 patients), 60 mg bid (202 patients) or placebo (218 patients). AZD9668
      showed no effect on lung function, respiratory signs and symptoms, QoL or
      biomarkers. At end of treatment, the change in mean pre-bronchodilator FEV1 for
      AZD9668 60 mg bid compared with placebo was 0.00L (95% confidence interval: 
      0.05, 0.04; p = 0.873). Overall, AZD9668 was well tolerated; the numbers of
      patients with adverse events (AEs), serious AEs and AEs leading to
      discontinuation were similar in each of the four study groups. AZD9668 60 mg bid
      showed no clinical benefit and no effect on biomarkers of inflammation or tissue
      degradation when added to tiotropium in patients with COPD. These results raise
      important questions for future investigation of anti-inflammatory and disease
      modifying agents in patients with COPD.

PMID- 22458941
TI  - Typing of the rabies virus in Chile, 2002-2008.
AB  - In Chile, dog rabies has been controlled and insectivorous bats have been
      identified as the main rabies reservoir. This study aimed to determine the rabies
      virus (RABV) variants circulating in the country between 2002 and 2008. A total
      of 612 RABV isolates were tested using a panel with eight monoclonal antibodies
      against the viral nucleoprotein (N-mAbs) for antigenic typing, and a product of
      320-bp of the nucleoprotein gene was sequenced from 99 isolates. Typing of the
      isolates revealed six different antigenic variants but phylogenetic analysis
      identified four clusters associated with four different bat species. Tadarida
      brasiliensis bats were confirmed as the main reservoir. This methodology
      identified several independent rabies enzootics maintained by different species
      of insectivorous bats in Chile.

PMID- 22458942
TI  - A texture-analysis-based design method for self-adaptive focus criterion
      function.
AB  - Autofocusing (AF) criterion functions are critical to the performance of a
      passive autofocusing system in automatic video microscopy. Most of the
      autofocusing criterion functions proposed are dependent on the imaging system and
      image captured by the objective being focused or ranged. This dependence
      destabilizes the performance of the system when the criterion functions are
      applied to objectives with different characteristics. In this paper, a new design
      method for autofocusing criterion functions is introduced. This method enables
      the system to have the ability to tell the texture directional information of the
      objective. Based on this information, the optimal focus criterion function
      specific to one texture direction is designed, voiding blindly using autofocusing
      functions which cannot perform well when applied to the certain surface and can
      even lead to failure of the whole process. In this way, we improved the self
      adaptability, robustness, reliability and focusing accuracy of the algorithm.
      First, the grey-level co-occurrence matrices of real-time images are calculated
      in four directions. Next, the contrast values of the four matrices are computed
      and then compared. The result reflects the directional information of the
      measured objective surfaces. Finally, with the directional information, an
      adaptive criterion function is constructed. To demonstrate the effectiveness of
      the new focus algorithm, we conducted experiments on different texture surfaces
      and compared the results with those obtained by existing algorithms. The proposed
      algorithm excellently performs with different measured objectives.

PMID- 22458940
TI  - Effect of bronchial colonisation on airway and systemic inflammation in stable
      COPD.
AB  - The recovery of potentially pathogenic microorganisms (PPMs) from bronchial
      secretions is associated with a local inflammatory response in COPD patients. The
      objective of this study was to determine the relationships between bronchial
      colonisation and both bronchial and systemic inflammation in stable COPD. In COPD
      patients recruited on first admission for an exacerbation, bacterial sputum
      cultures, interleukin (IL)-1beta, IL-6 and IL-8 levels, and blood C-reactive
      protein (CRP) were measured in stable condition. Bronchial colonisation was found
      in 39 of the 133 (29%) patients and was significantly related to higher sputum IL
      1beta (median [percentile 25-75]; 462 [121-993] vs. 154 [41-477] pg/ml, p =
      0.002), IL-6 (147 [71-424] vs. 109 [50-197] pg/ml, p = 0.047) and IL-8 values (15
      [9-19] vs. 8 [3-15] (*103) pg/ml, p = 0.002). Patients with positive cultures
      also showed significantly elevated levels of serum CRP (6.5 [2.5-8.5] vs. 3.5
      [1.7-5.4] mg/l, p = 0.016). Bronchial colonisation by Haemophilus influenzae was
      associated with higher levels of IL-1beta and IL-8 and clinically significant
      worse scores on the activity and impact domains of the St. George's Respiratory
      Questionnaire. In conclusion, bronchial colonisation is associated with bronchial
      inflammation and high blood CRP levels in stable COPD patients, being Haemophilus
      influenzae related to a more severe inflammatory response and impairment in
      health-related quality of life.

PMID- 22458944
TI  - Successful delivery in patients with FXIII deficiency receiving prophylaxis:
      report of 17 cases in Iran.
AB  - To prevent pregnancy loss in women with severe FXIII deficiency, prophylactic
      replacement therapy with a source of FXIII throughout pregnancy is essential. The
      aim of this study was to evaluate the bleeding score and rate of successful
      deliveries in FXIII-deficient pregnant Iranian women receiving regular
      prophylaxis. Seventeen FXIII-deficient women 18-35 years old (mean 24 years) were
      enrolled in the study. All patients except one had a history of at least one
      miscarriage. Patients received regular prophylaxis with 10 IU kg(-1) FXIII
      concentrate every 4 weeks before pregnancy and every 2 weeks during pregnancy for
      a period of 24-62 months. All bleeding episodes were recorded, and the bleeding
      score was determined on a standard form before and after the start of
      prophylaxis. After starting prophylaxis, monochloroacetic acid tests and 5 m urea
      tests were normal in all patients, and the bleeding score significantly decreased
      from 11-16 (mean 12 +/- 1.5) to 23 (mean 2.2 +/- 0.4) (P < 0.001). Thirteen minor
      bleeding episodes occurred during prophylaxis. All patients successfully
      delivered at 36 weeks' gestation and there were no significant coagulation
      complications during or after delivery. In this study, successful pregnancy
      maintenance and delivery were achieved in Iranian women with severe FXIII
      deficiency. Precise detection and diagnosis of this condition in women with
      coagulation disorders is essential to enable implementation of appropriate
      prophylaxis to prevent pregnancy loss.

PMID- 22458943
TI  - Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation.
AB  - BACKGROUND: Pannexin 1 forms ion and metabolite permeable hexameric channels and
      is abundantly expressed in the brain. After discovering pannexin 1 expression in
      postnatal neural stem and progenitor cells we sought to elucidate its functional
      role in neuronal development. RESULTS: We detected pannexin 1 in neural stem and
      progenitor cells in vitro and in vivo. We manipulated pannexin 1 expression and
      activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere
      cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell
      proliferation likely through the release of adenosine triphosphate (ATP).
      CONCLUSIONS: Permeable to ATP, a potent autocrine/paracine signaling metabolite,
      pannexin 1 channels are ideally suited to influence the behavior of neural stem
      and progenitor cells. Here we demonstrate they play a robust role in the
      regulation of neural stem and progenitor cell proliferation. Endogenous postnatal
      neural stem and progenitor cells are crucial for normal brain health, and their
      numbers decline with age. Furthermore, these special cells are highly responsive
      to neurological injury and disease, and are gaining attention as putative targets
      for brain repair. Therefore, understanding the fundamental role of pannexin 1
      channels in neural stem and progenitor cells is of critical importance for brain
      health and disease.

PMID- 22458946
TI  - Review: psychosocial interventions addressing sexual or relationship functioning
      in men with prostate cancer.
AB  - INTRODUCTION: Although previous research has evaluated the effectiveness of
      psychosocial interventions for men with prostate cancer, no previous review has
      investigated the effects of psychosocial interventions on both sexual and
      relationship functioning. AIM: To review the effectiveness of psychosocial
      interventions that focus on sexual and/or relationship functioning for men with
      prostate cancer and their partners. METHOD: A systematic literature review of
      research reported in the Medline, PsychINFO, PsychArticles databases from January
      1990 to September 10, 2011. MAIN OUTCOME MEASURE: The review focused on the
      evaluation of interventions that aimed to improve the sexual and/or relationship
      functioning of men and their partners. RESULTS: There was evidence that
      psychosocial interventions can improve men's sexual functioning, particularly
      when delivered face-to-face and when using more complex strategies to target
      sexuality in men and in relationships. There was inconclusive evidence for the
      effectiveness of psychosocial interventions in improving men's relationship
      functioning or the sexual or relationship functioning of their partners.
      CONCLUSIONS: There is a need for further research to target improving and
      measuring men and their partner's sexual and relationship functioning in the
      context of prostate cancer. The effectiveness of tailoring interventions to the
      specific needs of men and to their stage of cancer also needs to be further
      examined.

PMID- 22458947
TI  - Effect of different carbon substrates on nitrate stable isotope fractionation
      during microbial denitrification.
AB  - In batch experiments, we studied the isotope fractionation in N and O of
      dissolved nitrate during dentrification. Denitrifying strains Thauera aromatica
      and "Aromatoleum aromaticum strain EbN1" were grown under strictly anaerobic
      conditions with acetate, benzoate, and toluene as carbon sources. (18)O-labeled
      water and (18)O-labeled nitrite were added to the microcosm experiments to study
      the effect of putative backward reactions of nitrite to nitrate on the stable
      isotope fractionation. We found no evidence for a reverse reaction. Significant
      variations of the stable isotope enrichment factor epsilon were observed
      depending on the type of carbon source used. For toluene (epsilon(15)N, -18.1 +/-
      0.60/00 to -7.3 +/- 1.40/00; epsilon(18)O, -16.5 +/- 0.60/00 to -16.1 +/-
      1.50/00) and benzoate (epsilon(15)N, -18.9 +/- 1.30/00; epsilon(18)O, -15.9 +/-
      1.10/00) less negative isotope enrichment factors were calculated compared to
      those derived from acetate (epsilon(15)N, -23.5 +/- 1.90/00 to -22.1 +/- 0.80/00;
      epsilon(18)O, -23.7 +/- 1.80/00 to -19.9 +/- 0.80/00). The observed isotope
      effects did not depend on the growth kinetics which were similar for the three
      types of electron donors. We suggest that different carbon sources change the
      observed isotope enrichment factors by changing the relative kinetics of nitrate
      transport across the cell wall compared to the kinetics of the intracellular
      nitrate reduction step of microbial denitrification.

PMID- 22458948
TI  - Regional brain structural dysmorphology in human immunodeficiency virus
      infection: effects of acquired immune deficiency syndrome, alcoholism, and age.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection and alcoholism each
      carries liability for disruption of brain structure and function integrity.
      Despite considerable prevalence of HIV-alcoholism comorbidity, few studies
      examined the potentially heightened burden of disease comorbidity. METHODS:
      Participants were 342 men and women: 110 alcoholics, 59 with HIV infection, 65
      with HIV infection and alcoholism, and 108 healthy control subjects. This design
      enabled examination of independent and combined effects of HIV infection and
      alcoholism along with other factors (acquired immune deficiency syndrome [AIDS]
      defining events, hepatitis C infection, age) on regional brain volumes derived
      from T1-weighted magnetic resonance images. RESULTS: Brain volumes, expressed as
      Z scores corrected for intracranial volume and age, were measured in 20 tissue
      and 5 ventricular and sulcal regions. The most profound and consistent volume
      deficits occurred with alcohol use disorders, notable in the cortical mantle,
      insular and anterior cingulate cortices, thalamus, corpus callosum, and frontal
      sulci. The HIV-only group had smaller thalamic and larger frontal sulcal volumes
      than control subjects. HIV disease-related factors associated with greater volume
      abnormalities included CD4 cell count nadir, clinical staging, history of AIDS
      defining events, infection age, and current age. Longer sobriety and less
      lifetime alcohol consumption were predictive of attenuated brain volume
      abnormalities in both alcohol groups. CONCLUSIONS: Having HIV infection with
      alcoholism and AIDS had an especially poor outcome on brain structures. That
      longer periods of sobriety and less lifetime alcohol consumption were predictive
      of attenuated brain volume abnormalities encourages the inclusion of alcohol
      recovery efforts in HIV/AIDS therapeutic settings.

PMID- 22458950
TI  - Brain-derived neurotrophic factor in patients with chronic hepatitis C: beyond
      neurotrophic support.

PMID- 22458949
TI  - Abnormalities of the Duo/Ras-related C3 botulinum toxin substrate 1/p21-activated
      kinase 1 pathway drive myosin light chain phosphorylation in frontal cortex in
      schizophrenia.
AB  - BACKGROUND: Recent studies on GTPases have suggested that reduced Duo and cell
      division cycle 42 (Cdc42) transcript expression is involved in dendritic spine
      loss in schizophrenia. In murine models, Duo and Cdc42 phosphorylate p21
      activated kinase 1 (PAK1), which modifies the activity of regulatory myosin light
      chain (MLC) and cofilin by altering their phosphorylation. Therefore, we
      hypothesized that in schizophrenia abnormal Duo and Cdc42 expression result in
      changes in MLC and/or cofilin phosphorylation, which might alter actin
      cytoskeleton dynamics underlying dendritic spine maintenance. METHODS: We
      performed Western blot protein expression analysis in postmortem brains from
      patients diagnosed with schizophrenia and a comparison group. We focused our
      studies in the anterior cingulate cortex (ACC; n = 33 comparison group; n = 36
      schizophrenia) and dorsolateral prefrontal cortex (DLPFC; n = 29 comparison
      group; n = 35 schizophrenia). RESULTS: In both ACC and DLPFC, we found a
      reduction of Duo expression and PAK1 phosphorylation in schizophrenia. Cdc42
      protein expression was decreased in ACC but not in DLPFC. In ACC, we observed
      decreased PAK1 phosphorylation and increased MLC phosphorylation (pMLC), whereas
      in DLPFC pMLC remained unchanged. CONCLUSIONS: These data suggest a novel
      mechanism that might underlie dendritic spine loss in schizophrenia. The increase
      in pMLC seen in ACC might be associated with dendritic spine shrinkage. The lack
      of an effect on pMLC in DLPFC suggests that in schizophrenia PAK1 downstream
      pathways are differentially affected in these cortical areas.

PMID- 22458952
TI  - A review of the worldwide prevalence of vitiligo in children/adolescents and
      adults.
AB  - BACKGROUND: Vitiligo is an acquired, idiopathic, and worldwide common
      depigmentation disorder with an estimated prevalence from 0.1 to 8%. These
      numbers are based on clinical population studies and field research examining
      inhabitants of geographically enclosed areas. Our aim was to collect all
      available data on the prevalence of vitiligo in the general population, paying
      particular attention to children/adolescent groups and adults. MATERIALS AND
      METHODS: Screening of available literature and online databases using several key
      words. RESULTS: We found more than 50 studies that used several methods and
      subgroups of the general population. The prevalence of vitiligo ranges from 0.06
      to 2.28%, whereas this was 0.0-2.16% in children/adolescents populations.
      CONCLUSIONS: The often cited prevalence of 8% could not be confirmed after
      excluding clinical patient populations. Accordingly, the worldwide prevalence of
      vitiligo ranges between 0.5 and 2%.

PMID- 22458953
TI  - Current trends in nursing theories.
AB  - PURPOSE: To explore current trends in nursing theories through an integrated
      literature review. ORGANIZING CONSTRUCT AND METHODS: The literature related to
      nursing theories during the past 10 years was searched through multiple databases
      and reviewed to determine themes reflecting current trends in nursing theories.
      FINDINGS: The trends can be categorized into six themes: (a) foci on specifics;
      (b) coexistence of various types of theories; (c) close links to research; (d)
      international collaborative works; (e) integration to practice; and (f) selective
      evolution. CONCLUSIONS: We need to make our continuous efforts to link research
      and practice to theories, to identify specifics of our theories, to develop
      diverse types of theories, and to conduct international collaborative works.
      CLINICAL RELEVANCE: Our paper gives implications for future theoretical
      development in diverse clinical areas of nursing research and practice.

PMID- 22458951
TI  - The role of ghrelin in reward-based eating.
AB  - The peptide hormone ghrelin acts in the central nervous system as a potent
      orexigenic signal. Not only is ghrelin recognized as playing an important role in
      feeding circuits traditionally thought of as affecting body weight homeostasis,
      but also an accumulating number of scientific studies have identified ghrelin as
      being a key regulator of reward-based, hedonic eating behaviors. In the current
      article, we review ghrelin's orexigenic actions, the evidence linking ghrelin to
      food reward behavior, potential mechanisms by which ghrelin mediates reward-based
      eating behavior, and those studies suggesting an obligatory role for ghrelin in
      the changed eating behaviors induced by stress.

PMID- 22458954
TI  - Mortality in cancer patients with a history of cutaneous squamous cell carcinoma-
      a nationwide population-based cohort study.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is associated with underlying
      immunosuppression, so it may be a prognostic marker in patients with subsequent
      cancer. We therefore conducted a nationwide population-based Danish cohort study
      to evaluate whether a history of cutaneuos SCC has prognostic impact in patients
      with one of the following index cancers: non-Hodgkin's lymphoma (NHL), or cancer
      of the lung, colon, rectum, breast, or prostate. METHODS: We used Danish medical
      databases, which cover the entire Danish population of 5.6 million inhabitants
      and linked them using the unique personal identification number assigned to all
      Danish residents. From 1982 through 2003, we identified 745 index cancer patients
      with and 79,143 without previous cutaneous SCC. Using Cox proportional hazards
      regression, we calculated adjusted mortality rate ratios (MRRs) with 95%
      confidence intervals (CIs). RESULTS: Overall, previous SCC was associated with an
      increased mortality of cancer (MRR 1.13, 95% CI: 1.04-1.23). When examining index
      cancers separately, increased MRRs were found for cancer of the lung (MRR 1.23,
      95% CI: 1.05-1.43), colon (MRR 1.13, 95% CI: 0.92-1.40), rectum (MRR 1.29, 95%
      CI: 1.00-1.67), breast (MRR 1.09, 95% CI: 0.82-1.43), and NHL (MRR 1.09, 95% CI:
      0.81-1.47), but not for prostate cancer (MRR 0.99, 95% CI: 0.83-1.18).
      CONCLUSIONS: Our results suggest that previous cutaneous SCC is associated with
      poor prognosis of some cancers. This finding stresses the importance of adherence
      to the existing recommendations of screening, diagnosis, and treatment of cancer
      in patients with a history of SCC.

PMID- 22458955
TI  - Cell-based therapy for epithelial wounds.
AB  - BACKGROUND AIMS: Bone marrow-derived cells (BMDC) form a significant portion of
      regenerating epithelial tissue. The purpose of this study was to determine
      whether exogenous BMDC (containing stroma, stem and progenitor cells), introduced
      systemically or within the injury site, could enhance the injury repair response.
      METHODS: Excisional wounds (10-mm diameter) were treated by systemic
      (intravenous; i.v.) and local (subcutaneous; s.c.) administration of BMDC (10-20
      * 10(6)/100 MUL phosphate-buffered saline). Young and aged BMDC and recipients
      were studied. RESULTS: Young BMDC (2 months old) increased the healing rate
      compared with older BMDC (1 year old), as measured by the rate of healing and the
      percentage of healed tissue. Young recipients had statistically better healing
      efficiency than older recipients. When old BMDC were used, young recipients had a
      better healing ability than older recipients. In addition, when the size of the
      healed tissue, the area of repigmentation and hair growth at the injury site were
      compared, young BMDC and young recipients had superior effects compared with old
      BMDC and old recipients. CONCLUSIONS: These results demonstrate that cellular
      therapy is important for wound healing in older recipients that do not heal
      significantly without intervention. BMDC injections result in normal healing,
      indistinguishable from young recipients. Significantly, a single injection into
      the wound margin is sufficient to reverse the wounding process and promote normal
      wound healing. Although younger recipients eventually healed without therapy,
      BMDC injections accelerated the process, reduced scarring and increased hair
      regrowth. These findings provide insight into the treatment of non-healing
      epithelial tissue with BMDC.

PMID- 22458957
TI  - Mesenchymal stromal cells and fibroblasts: a case of mistaken identity?
AB  - The plastic-adherent fibroblast-looking cells that can be isolated and culture
      expanded from bone marrow and many other tissues are widely known as mesenchymal
      stromal cells (MSC). In addition to their fibroblast-like morphology, they are
      characterized by a panel of cell-surface markers and their potential to
      differentiate into bone, fat and cartilage. Based on their intriguing
      immunomodulatory and regenerative properties, MSC are being investigated as
      cellular therapeutics for a variety of clinical indications. However, many
      questions regarding the true identity and functionality of these cells in vivo
      remain unanswered. Fibroblasts, known for a much longer time but still poorly
      characterized, are also considered to be a ubiquitous stromal element of almost
      all tissues and are believed to play a role in tissue homeostasis. Despite the
      presence of MSC and fibroblasts in almost all tissues, similar morphology and
      other shared characteristics, the exact relationship between MSC and fibroblasts
      has remained undetermined. In this review, based on recent and old, but often
      neglected, literature it is suggested that ex vivo culture-expanded MSC and
      fibroblasts are indistinguishable by morphology, cell-surface markers,
      differentiation potential and immunologic properties.

PMID- 22458956
TI  - A clinically adaptable method to enhance the cytotoxicity of natural killer cells
      against B-cell malignancies.
AB  - BACKGROUND AIMS: Retroviral transduction of anti-CD19 chimeric antigen receptors
      significantly enhances the cytotoxicity of natural killer (NK) cells against B
      cell malignancies. We aimed to validate a more practical, affordable and safe
      method for this purpose. METHODS: We tested the expression of a receptor
      containing CD3zeta and 4-1BB signaling molecules (anti-CD19-BB-zeta) in human NK
      cells after electroporation with the corresponding mRNA using a clinical-grade
      electroporator. The cytotoxic capacity of the transfected NK cells was tested in
      vitro and in a mouse model of leukemia. RESULTS: Median anti-CD19-BB-zeta
      expression 24 h after electroporation was 40.3% in freshly purified (n =18) and
      61.3% in expanded (n = 31) NK cells; median cell viability was 90%. NK cells
      expressing anti-CD19-BB-zeta secreted interferon (IFN)-gamma in response to CD19
      positive target cells and had increased cytotoxicity. Receptor expression was
      detectable 6 h after electroporation, reaching maximum levels at 24-48 h;
      specific anti-CD19 cytotoxicity was observed at 96 h. Levels of expression and
      cytotoxicities were comparable with those achieved by retroviral transduction. A
      large-scale protocol was developed and applied to expanded NK cells (median NK
      cell number 2.5 * 10(8), n = 12). Median receptor expression after 24 h was
      82.0%; NK cells transfected under these conditions exerted considerable
      cytotoxicity in xenograft models of B-cell leukemia. CONCLUSIONS: The method
      described here represents a practical way to augment the cytotoxicity of NK cells
      against B-cell malignancies. It has the potential to be extended to other targets
      beyond CD19 and should facilitate the clinical use of redirected NK cells for
      cancer therapy.

PMID- 22458958
TI  - Development and validation of a multiplex quantitative polymerase chain reaction
      assay for the detection of Mollicutes impurities in human cells, cultured under
      good manufacturing practice conditions, and following European Pharmacopoeia
      requirements and the International Conference on Harmonization guidelines.
AB  - BACKGROUND AIMS: The clinical applications of in vitro manipulated cultured cells
      and their precursors are often made use of in therapeutic trials. However, tissue
      cultures can be easily contaminated by the ubiquitous Mollicutes micro-organisms,
      which can cause various and severe alterations in cellular function. Thus methods
      able to detect and trace Mollicutes impurities contaminating cell cultures are
      required before starting any attempt to grow cells under good manufacturing
      practice (GMP) conditions. METHODS: We developed a multiplex quantitative
      polymerase chain reaction (qPCR) assay specific for the 16S-23S rRNA intergenic
      spacer regions, for the Tuf and P1 cytoadhesin genes, able to detect contaminant
      Mollicutes species in a single tube reaction. The system was validated by
      analyzing different cell lines and the positive samples were confirmed by 16S and
      P1 cytoadhesin gene dideoxy sequencing. RESULTS: Our multiplex qPCR detection
      system was able to reach a sensitivity, specificity and robustness comparable
      with the culture and the indicator cell culture method, as required by the
      European Pharmacopoeia guidelines. CONCLUSIONS: We have developed a multiplex
      qPCR method, validated following International Conference on Harmonization (ICH)
      guidelines, as a qualitative limit test for impurities, assessing the validation
      characteristics of limit of detection and specificity. It also follows the
      European Pharmacopoeia guidelines and Food and Drug Administration (FDA)
      requirements.

PMID- 22458959
TI  - In-car countermeasures open window and music revisited on the real road: popular
      but hardly effective against driver sleepiness.
AB  - This study investigated the effects of two very commonly used countermeasures
      against driver sleepiness, opening the window and listening to music, on
      subjective and physiological sleepiness measures during real road driving. In
      total, 24 individuals participated in the study. Sixteen participants received
      intermittent 10-min intervals of: (i) open window (2 cm opened); and (ii)
      listening to music, during both day and night driving on an open motorway. Both
      subjective sleepiness and physiological sleepiness (blink duration) was estimated
      to be significantly reduced when subjects listened to music, but the effect was
      only minor compared with the pronounced effects of night driving and driving
      duration. Open window had no attenuating effect on either sleepiness measure. No
      significant long-term effects beyond the actual countermeasure application
      intervals occurred, as shown by comparison to the control group (n = 8). Thus,
      despite their popularity, opening the window and listening to music cannot be
      recommended as sole countermeasures against driver sleepiness.

PMID- 22458960
TI  - Vascular endothelial (VEGF) and epithelial growth factor (EGF) as well as
      platelet-activating factor (PAF) and receptors are expressed in the early
      pregnant canine uterus.
AB  - The aim of this study was to investigate the course of expression of platelet
      activating factor (PAF), PAF-receptor (PAF-R), epidermal growth factor (EGF), EGF
      R, vascular endothelial growth factor (VEGF), VEGF-R1 and VEGF-R2 in uterine
      tissue during canine pregnancy. For this purpose, 20 bitches were
      ovariohysterectomized at days 10-12 (n = 10), 18-25 (n = 5) and 28-45 (n = 5)
      days after mating, respectively. The pre-implantation group was proven pregnant
      by embryo flushing of the uterus after the operation, the others by sonography.
      Five embryo negative, that is, non-pregnant, bitches in diestrus (day 10-12)
      served as controls. Tissue samples from the uterus (placentation sites and horn
      width, respectively) were excised and snap-frozen in liquid nitrogen after
      embedding in Tissue Tec((r)). Extraction of mRNA for RT-PCR was performed with
      Tri-Reagent. In the embryos, mRNA from all factors except VEGF was detected. In
      the course of pregnancy, significantly higher expression of PAF and PAFR as well
      as VEGF and VEGFR2 during the pre-implantation stage than in all other stages and
      a strong upregulation of EGF during implantation were characteristic. The course
      of EGF was in diametrical opposition to the course of the receptor. These results
      point towards an increased demand for VEGF, EGF and PAF during the earliest
      stages of canine pregnancy.

PMID- 22458962
TI  - Delayed crystallization of ultrathin Gd2O3 layers on Si(111) observed by in situ
      X-ray diffraction.
AB  - We studied the early stages of Gd2O3 epitaxy on Si(111) in real time by
      synchrotron-based, high-resolution X-ray diffraction and by reflection high
      energy electron diffraction. A comparison between model calculations and the
      measured X-ray scattering, and the change of reflection high-energy electron
      diffraction patterns both indicate that the growth begins without forming a three
      dimensional crystalline film. The cubic bixbyite structure of Gd2O3 appears only
      after a few monolayers of deposition.

PMID- 22458961
TI  - Restless legs syndrome during and after pregnancy and its relation to snoring.
AB  - OBJECTIVE: To study development of restless legs syndrome (RLS) during and after
      pregnancy, and whether RLS is related to snoring or other pregnancy-related
      symptoms. DESIGN: Prospective study. SETTING: Antenatal care clinics in the
      catchment area of Linkoping university hospital, Sweden. POPULATION: Five hundred
      consecutively recruited pregnant women. METHODS: Sleep disturbances, including
      symptoms of RLS and snoring, were assessed with questionnaires in each trimester.
      A complementary questionnaire was sent three years after delivery to women
      experiencing symptoms of RLS during pregnancy. MAIN OUTCOME MEASURES: Symptoms of
      RLS in relation to snoring in each trimester. RESULTS: Symptoms of RLS were
      reported by 17.0% of the women in the first trimester, by 27.1% in the second
      trimester and by 29.6% in the third trimester. Snoring in the first trimester was
      correlated to increased prevalence of RLS in all three trimesters (p= 0.003,
      0.017 and 0.044 in the first, second and third trimester, respectively). No
      correlation was found between RLS and anemia, parity or body mass index. Among
      the women who experienced RLS, 31% still had symptoms three years after delivery.
      Fifty-eight per cent of those whose symptoms had disappeared stated that this
      happened within one month after delivery. CONCLUSIONS: Symptoms of RLS progressed
      most between the first and second trimester. Women who snored in the first or
      second trimester of pregnancy had a higher prevalence of RLS in the third
      trimester, which indicates that snoring in early pregnancy might predict RLS
      later. Symptoms of RLS disappear quite soon after delivery, but about one-third
      of women with RLS during pregnancy may still have symptoms three years after
      childbirth.

PMID- 22458963
TI  - Influence of combustion conditions on hydrophilic properties and microstructure
      of flame soot.
AB  - Previous studies suggest that structure and reactivity of soot depend on
      combustion conditions like the fuel/oxygen ratio and nature of fuels. However,
      the essence of how combustion conditions affect physical and chemical properties
      of soot is still an open question. In this study, soot samples were prepared by
      combusting toluene, n-hexane, and decane under controlled conditions, and their
      hydrophilic properties, morphology, microstructure, content of volatile organic
      compounds, and functional groups were characterized. The hydrophilicity of n
      hexane and decane flame soot increased with decreasing fuel/oxygen ratio, while
      it almost did not change for toluene flame soot. Fuel/oxygen ratio had little
      effect on the morphology of aggregates and the graphite crystallite size. The
      primary particle size and the content of volatile organic compounds on soot
      decreased with decreasing fuel/oxygen ratio. Less hydrophobic groups (C-H) and
      more hydrophilic groups (C?O) were observed on lean n-hexane and decane flame
      soot than that on the corresponding rich flame soot. Volatile organic compounds
      had little effect on the hydrophilicity of soot while the hydrophilicity
      correlated linearly with the ratio of C?O content to C-H content. The hydrophilic
      functional groups were found to be mainly located at graphene layer edges and on
      surface graphene layers in soot.

PMID- 22458965
TI  - An on-line high performance liquid chromatography-crocin bleaching assay for
      detection of antioxidants.
AB  - An on-line HPLC (high performance liquid chromatography) method for the rapid
      screening of individual antioxidants in mixtures was developed using crocin as a
      substrate (i.e. oxidation probe) and 2,2'-azobis(2-amidinopropane dihydrochloride
      (AAPH)) in phosphate buffer (pH 7.5) as a radical generator. The polyene
      structure of crocin and AAPH-derived peroxyl radicals resemble the lipidic
      substrates and radicals found in true food more closely than the popular, albeit
      artificial, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS(+) (2,2-azinobis-(3
      ethylbenzothiazoline-6-sulfonate)) do. After separation by a C18 (octadecyl
      silica) column and UV (ultraviolet) detection, antioxidative analytes react with
      peroxyl radicals at 90 degrees C and the inhibition of crocin oxidation (i.e.
      bleaching) is detected as a positive peak by an absorbance detector at 440 nm.
      The method is simple, uses standard instruments and inexpensive reagents. It can
      be applied for isocratic HPLC runs using mobile phases containing 10-90% organic
      solvent in water, weak acids or buffers (pH 3.5-8.5). With baseline correction,
      gradient runs are also feasible. The radical scavenging activity of several
      natural antioxidants and a green tea extract was studied. After optimisation of
      conditions such as reagent concentrations and flows, the limit of detection
      varied from 0.79 to 7.4 ng, depending on the antioxidant.

PMID- 22458964
TI  - Stir bar sorptive extraction and high performance liquid chromatographic
      determination of carvedilol in human serum using two different polymeric phases
      and an ionic liquid as desorption solvent.
AB  - This article presents a method employing stir bar coated with a film of poly
      (methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and
      polydimethylsiloxane (PDMS) in combination with liquid desorption (LD) using
      ionic liquid, followed by high performance liquid chromatography (HPLC) equipped
      with ultraviolet (UV) detection for the determination of carvedilol in human
      serum samples. Stir bar sorptive extraction (SBSE) variables, such as desorption
      and extraction time and temperature, desorption solvent and pH of the matrix were
      optimized, in order to achieve suitable analytical sensitivity in a short period
      of time. Also, the concentration effect of 1-methyl-3-octylimidazolium
      tetrafluoroborate [Omim][BF4] ionic liquid on the efficiency of LD was
      investigated. A comparison between PA-EG/SBSE and PDMS/SBSE was made by
      calculating the experimental recovery and partition coefficient (K), where PA-EG
      phase demonstrated to be an excellent alternative for the enrichment of the
      carvedilol from serum samples. The effect of [Omim][BF4] on carryover was studied
      and no carryover was observed. Under optimized experimental conditions, the
      analytical performance showed excellent linear dynamic range, with correlation
      coefficients higher than 0.999 and limits of detection and quantification of 0.3
      and 1.0 ng mL(-1), respectively. Intra- and inter-day recovery ranged from 94 to
      103% and the coefficients of variations were less than 3.2%. The proposed method
      was shown to be simple, highly sensitive and suitable for the measurement of
      trace concentration levels of carvedilol in biological fluid media.

PMID- 22458966
TI  - Bioactivity-guided fractionation of the volatile oil of Angelica sinensis radix
      designed to preserve the synergistic effects of the mixture followed by
      identification of the active principles.
AB  - In natural product research, it is a common experience that fractionation of
      biologically-active crude extracts can lead to the loss of their original
      activity. This is attributed to synergistic effects, where two or more components
      are required to be present together for full activity of the sample. Our previous
      study showed that a volatile oil of Angelica sinensis radix (VOAS) inhibited
      endothelial cell proliferation in culture. Here we have used a bioactivity-guided
      fractionation method to preserve any synergistic effects of VOAS combining
      countercurrent chromatography (CCC), the MTS cell viability assay and gas
      chromatography (GC). Using a two-phase CCC solvent system (heptane-ethyl acetate
      methanol-water at a volume ratio of 27:23:27:23%), forty-five fractions were
      isolated, nine of which exhibited anti-endothelial properties. GC analysis showed
      two bioactive alkylphthalides, Z-ligustilide and n-butylidenephthalide (BP) were
      the major compounds detected in the bioactive fractions, and were absent in non
      bioactive fractions. Our results indicate that Z-ligustilide and BP are the main
      constituents responsible for the anti-endothelial properties of VOAS. This rapid
      and reliable approach in preserving sample activity while isolating and
      identifying its active compounds suggests that this protocol can be a powerful
      tool for drug discovery from natural products.

PMID- 22458967
TI  - Chromatographic examination of the chemical composition and sequence distribution
      of copolymers from ethyl and benzyl diazoacetate.
AB  - Polymers, especially copolymers, are highly complex samples and, therefore,
      require various setups for their thorough characterization. In this work, one-
      and two-dimensional chromatographic approaches were applied to characterize two
      homopolymers and two dissimilar copolymers prepared by rhodium-mediated carbene
      polymerization using ethyl and benzyl diazoacetate as the monomers: poly-(EA-ran
      BnA) and poly((EA)(b)-(BnA-ran-EA)(b)). Different strategies of synthesis
      suggested that poly-(EA-ran-BnA) was an approximately 1:1 random copolymer and
      that poly((EA)(b)-(BnA-ran-EA)(b)) was a block-type copolymer of which the (BnA
      ran-EA)(b) block is dominated by BnA. The hydrodynamic volume of the investigated
      polymers turned out to be comparable, i.e. size exclusion chromatography (SEC)
      did not separate them. Temperature-gradient interaction chromatography was not
      feasible and one-dimensional (solvent-)gradient-elution liquid chromatography
      (GELC) suffered from coelution problems. Pyrolysis-gas-chromatography (Py-GC-MS)
      experiments allowed determining the monomer ratio. SEC with UV and refractive
      index detection indicated the presence of molecular-weight-dependent chemical
      heterogeneity for the poly((EA)(b)-(BnA-ran-EA)(b)) copolymer. This finding was
      confirmed with off-line SEC//Py-GC-MS. Only a comprehensive two-dimensional
      GELC*SEC setup enabled the separation of high-molecular-weight material of the
      less-retained homopolymer from low-molecular-weight copolymeric material. In this
      way it was possible to detect some high-molecular-weight homopolymeric material
      in one of the copolymers.

PMID- 22458968
TI  - Validation of thermally assisted hydrolysis and methylation-gas chromatography
      using a vertical microfurnace pyrolyzer for the compositional analysis of Fatty
      Acid components in microalgae.
AB  - Thermally assisted hydrolysis and methylation-gas chromatography (THM-GC) in the
      presence of trimethylsulfonium hydroxide, using a vertical microfurnace
      pyrolyzer, was validated for the compositional analysis of fatty acid components
      in microalgae. The chromatograms of a microalga,  Pavlova lutheri , obtained
      under optimized THM conditions clearly showed a series of fatty acid methyl
      esters including thermally labile polyunsaturated fatty acid components. On the
      basis of these peak areas, their chemical compositions were rapidly determined
      without using any tedious sample pretreatment with a precision of <8% relative
      standard deviation. Moreover, the compositions thus obtained were in good
      agreement with those obtained by the conventional technique involving solvent
      extraction. Finally, the THM-GC technique was applied for the compositional
      analysis of fatty acid components in a newly found microalga,  Coccomyxa
      gloeobotrydiformis . The obtained data showed a high abundance (24 mol %) of
      alpha-linolenic acid components, suggesting its potential usefulness as feed
      sources and/or functional foods.

PMID- 22458969
TI  - Functionally important amino acids in rice sucrose transporter OsSUT1.
AB  - Six conserved, charged amino acids within membrane spans in rice sucrose
      transporter OsSUT1 were identified using a three-dimensional structural model
      based on the crystal structures of three major facilitator superfamily (MFS)
      proteins: LacY, GlpT, and EmrD. These positions in OsSUT1 were selected for
      mutagenesis and biochemical assays. Among the six mutants, D177N completely lost
      transport function, D331N retained only a small fraction of sucrose uptake
      activity (2.3% of that of the wild type), and R335H and E336Q also displayed a
      substantial decrease in transport activity. D329N functioned as well as wild-type
      OsSUT1. R188K did not transport sucrose but showed a H(+) leak that was inhibited
      by sucrose, indicating that R188K had uncoupled sucrose and H(+) translocation.
      This demonstrates that charged amino acids within membrane spans are important
      for the transport mechanism of OsSUT1 as they are in lactose permease.

PMID- 22458970
TI  - Does perinatal exposure to endocrine disruptors induce autism spectrum and
      attention deficit hyperactivity disorders? Review.
AB  - AIM: To provide an overview of studies on perinatal exposure in humans to
      endocrine disrupting chemicals (EDCs) in relation to autism spectrum (ASD) and
      attention deficit hyperactivity (ADHD) disorders. METHODS: A review of the
      literature (PubMed) was performed. Exposure-related keywords, including various
      chemicals, were matched with keywords describing outcome. Animal studies as well
      as publications not written in English were excluded. In total, 834 titles were
      retrieved. The final selection included 21 publications. RESULTS: Positive
      associations were found for ASD in relation to exposure to all chemicals
      investigated, which included hazardous air pollutants, pesticides and bisphenol A
      (BPA). Increased risks of ADHD or positive associations were found for exposure
      to polychlorinated biphenyls (PCBs), dialkyl phosphate (DAP) and chlorpyrifos.
      BPA, polybrominated diphenylethers (PBDEs) and low molecular weight (LMW)
      phthalates were positively associated with externalizing behaviour. Five of 17
      studies did not find any association between exposure and ADHD. CONCLUSION:
      Perinatal exposure to EDCs appears to be associated with the occurrence of ASD as
      well as ADHD. Disruption of thyroid hormone function and gamma-aminobutyric acid
      (GABA)ergic mechanisms may offer an explanation for the observed relations;
      though, conclusive evidence in humans is limited.

PMID- 22458971
TI  - Prophylactic central neck dissection in differentiated thyroid cancer: a
      procedure in search of an indication.

PMID- 22458972
TI  - Potassium iodide prophylaxis: what have we learned and questions raised by the
      accident at the Fukushima Daiichi Nuclear Power Plant.

PMID- 22458973
TI  - Graves' disease presenting with severe cholestasis.
AB  - BACKGROUND: Hyperthyroidism has been associated with liver function
      abnormalities; however, cholestasis as the presenting feature of adolescent
      Graves' disease has not been previously reported. PATIENT SUMMARY: The patient
      was a 17-year-old girl who presented with severe cholestasis and was found to
      have Graves' disease. She also had a positive hepatitis A immunoglobulin M
      antibody but her clinical course, the liver histopathology, and her mildly
      elevated transaminases indicated that the acute hepatitis A infection was not
      dominant at the time of presentation with severe cholestasis. Other causes of
      cholestasis, including congestive heart failure, autoimmune hepatitis, and viral
      infection, were excluded. Treatment with methimazole resolved the
      hyperthyroidism, and the cholestasis improved, as well. CONCLUSION: Severe
      cholestasis is a rare presenting feature of Graves' disease. With careful
      monitoring, methimazole can be used to treat the hyperthyroidism in the setting
      of cholestasis.

PMID- 22458976
TI  - Survival in patients with incident dementia compared with a control group: a five
      year follow-up.
AB  - BACKGROUND: Dementia is an important disease in older age. Existing studies on
      dementia mortality face limitations. For instance, they are based on prevalent,
      small, or geographically limited samples or do not include controls. We aimed to
      study survival after the first diagnosis of dementia compared with a control
      group. METHODS: We analyzed claims data of a German health insurance company,
      including 1,818 incident dementia cases and 7,235 age- and sex-matched non
      dementia controls (53% male; mean age 78.8 years). The follow-up was five years.
      We assessed survival with the Kaplan-Meier curves and performed Cox proportional
      hazard regression, also including nursing care dependency and comorbidities.
      RESULTS: The cumulative five-year mortality was 53.5% in the dementia cases and
      31.1% in the control group (hazard ratio: 2.1). Even after adjusting for
      comorbidities and nursing care, the mortality risk was 1.5 times higher for
      patients with incident dementia than for controls. Nursing care dependency showed
      high influence on mortality, likewise in dementia patients and controls.
      CONCLUSIONS: Although some factors, such as education or the type and severity of
      dementia, could not be included in the analyses, our study shows a clear
      influence of dementia on mortality irrespective of age, sex, care dependency, and
      comorbidities. The strongest influence on mortality was found for dementia
      patients with nursing care dependency. Taking into account their mortality of
      around 70% in care level 1 and up to 80% in care levels 2 and 3, healthcare
      delivery to these patient groups should strongly consider elements of palliative
      care focusing on the quality of life.

PMID- 22458977
TI  - A promising new wavelength region for three-photon fluorescence microscopy of
      live cells.
AB  - We report three-photon laser scanning microscopy (3PLSM) using a bi-directional
      pumped optical parametric oscillator (OPO) with signal wavelength output at
      lambda= 1500 nm. This novel laser was used to overcome the high optical loss in
      the infrared spectral region observed in laser scanning microscopes and objective
      lenses that renders them otherwise difficult to use for imaging. To test our
      system, we performed 3PLSM auto-fluorescence imaging of live plant cells at
      lambda= 1500 nm, specifically Spirogyra, and compared performance with two-photon
      excitation (2PLSM) imaging using a femtosecond pulsed Ti:Sapphire laser at
      lambda= 780 nm. Analysis of cell viability based on cytoplasmic organelle
      streaming and structural changes of cells revealed that at similar peak powers,
      2PLSM caused gross cell damage after 5 min but 3PLSM showed little or no
      interference with cell function after 15 min. The lambda= 1500 nm OPO is thus
      shown to be a practical laser source for live cell imaging.

PMID- 22458978
TI  - E-learning improves knowledge and practical skills in haemophilia patients on
      home treatment: a randomized controlled trial.
AB  - Home treatment of haemophilia is currently the standard of care for patients with
      severe haemophilia. Home treatment increases the responsibility of the patients
      for their own treatment and care. Therefore, it is of utmost importance to attain
      a high level of knowledge and practical skills. The aim of our study was to
      investigate whether or not an educational e-learning program improves knowledge
      and skills of adult patients with haemophilia on home treatment. Participants
      treated at the Haemophilia Treatment Center of the Erasmus University Medical
      Centre completed a questionnaire to test their knowledge of haemophilia,
      treatment of bleedings and of complications of treatment and were observed during
      the intravenous injection of clotting factor concentrate, using a standardized
      scoring list. Afterwards they were randomized to follow an e-learning program or
      no intervention (control group). After 1 month they completed the same
      questionnaire again and practical skills were scored once more. At baseline,
      haemophilia patients (n = 30) scored 24 of 48 questions in the questionnaire
      correctly. Seventy-five per cent of the items on the practical skills scoring
      list were performed correctly. One month later, the e-learning group (n = 16; 36;
      18-45) showed a higher level of theoretical knowledge compared to the control
      group (n = 14; 26; 19-32; P < 0.001). Also practical skills were significantly
      better in the group that followed the e-learning program compared to the control
      group (respectively P = 0.002). Self-efficacy of 90% vs. 80% the patients with
      haemophilia was high in all patients. Our study shows that in haemophilia
      patients with haemophilia, who are on home treatment, knowledge of haemophilia
      treatment and complications as well as practical skills can be improved by an
      educational e-learning program.

PMID- 22458979
TI  - Fc receptor like 3 in Chinese patients of Han nationality with Guillain-Barre
      syndrome.
AB  - Fc receptor like 3 gene (FcRL3) has been associated with some autoimmune
      diseases. Here, its role in Guillain-Barre syndrome (GBS) was evaluated by
      studying nine FcRL3 gene SNPs in a Chinese cohort of GBS patients. The
      frequencies of FcRL3-3-169C, FcRL3-6 intron3A, and FcRL3-8 exon15G alleles were
      significantly increased in GBS patients compared with healthy controls. The
      frequency of FcRL3-1->9 CCTGGAGAA haplotype was significantly increased, and the
      frequencies of FcRL3-1->9 CCTACAAAA,CCCACGAAA, and CCTGCGGAA haplotypes were
      significantly decreased compared with healthy controls. These results suggest
      that FcRL3 is associated with GBS incidence.

PMID- 22458981
TI  - Association of transforming growth factor beta-1 (TGFB1) regulatory region
      polymorphisms with myasthenia gravis-related ophthalmoparesis.
AB  - We investigated the association of an ophthalmoplegic complication developing in
      African myasthenia gravis (MG) subjects with polymorphisms in the regulatory
      region of TGFB1. We found significant associations with several putative
      functional single nucleotide polymorphisms (SNPs) (including two novel SNPs) that
      potentially alter transcription factor binding. Our data support a hypothesis
      that altered TGFB1 regulation may predispose individuals who harbour these SNPs
      to developing ophthalmoplegia as a result of increased TGF-beta1 driven
      myofibrosis as a consequence to complement-mediated damage.

PMID- 22458980
TI  - Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes
      of multiple sclerosis subjects.
AB  - The protein tyrosine phosphatase, SHP-1, is a negative regulator of
      proinflammatory signaling and autoimmune disease. We have previously reported
      reduced SHP-1 expression in peripheral blood leukocytes of subjects with multiple
      sclerosis (MS). Recent evidence indicates that virus-induced DNA methylation of
      the SHP-1 promoter is responsible for aberrant silencing of SHP-1 expression and
      function in hematopoietic cells that might relate to inflammatory diseases. In
      the present study, bisulfite sequencing of the SHP-1 promoter demonstrated that
      over a third of MS subjects had abnormally high promoter methylation. As SHP-1 is
      deficient in MS leukocytes and SHP-1-regulated proinflammatory genes are
      correspondingly upregulated, we propose that increased SHP-1 promoter methylation
      may relate in part to decreased SHP-1 expression and increased leukocyte-mediated
      inflammation in MS.

PMID- 22458982
TI  - Neuroprotective effects of human umbilical cord mesenchymal stromal cells in an
      immunocompetent animal model of Parkinson's disease.
AB  - Microglial activation in the substantia nigra (SN) is a ubiquitous feature in PD
      which could mediate toxic effects. Human mesenchymal stromal cells (hMSCs)
      possess immunomodulatory properties. We evaluated whether the transplantation of
      hMSCs obtained from umbilical cord had a neuroprotective effect in a not
      immunosuppressed rat Parkinson's disease (PD) model. Rats receiving hMSCs in the
      SN displayed significant preservation in the number of dopaminergic neurons in
      the SN at 21 days after lesion and an improved performance in behavioral tests
      compared to control rats. However, no differences in any inflammatory parameter
      tested were found. These results suggest that grafted hMSCs exert neuroprotection
      but not neuromodulatory effects on degenerating dopaminergic neurons.

PMID- 22458983
TI  - Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia
      in vitro.
AB  - B cells are important in the pathogenesis of multiple sclerosis (MS) and some of
      the effects are not dependent on maturation of B cells into immunoglobulin (Ig)
      producing plasmablasts and plasma cells. B cells present antigen, activate T
      cells, and are involved in immunoregulation and cytokine secretion. To determine
      if B cells from MS patients secrete products that have deleterious effects on
      glial cells not mediated by Ig, and to compare effects with secretory products of
      normal controls (NC), we isolated B cells from 7 patients with relapsing
      remitting MS (RRMS) and 4 NC. B cells were cultured alone or after stimulation
      with CD40 ligand (CD40L), CD40L+cross-linking of the B cell antigen receptor
      (xBCR) and CD40L+xBCR+stimulation of toll like receptor 9 (TLR9). Supernatants
      were harvested and incubated with mixed central nervous system (CNS) neonatal rat
      glial cells. Supernatants from unstimulated NC B cells induced on average death
      of 7% (range 0-24%) of differentiated oligodendrocytes (OL); in contrast,
      supernatants from unstimulated B cells from RRMS patients induced death of 57%
      (range 35-74%) of OL. Supernatants of stimulated B cells from NC did not increase
      the minimal OL death whereas stimulation of B cells from RRMS had variable
      results compared to unstimulated B cells. Supernatants from both NC and RRMS
      induced microglial enlargement and loss of normal resting bipolar morphology. OL
      death did not correlate with levels of tumor necrosis alpha (TNF-alpha),
      lymphotoxin alpha (LT-alpha), interleukin 6 (IL-6), IL-10, transforming growth
      factor beta 1 (TGF-beta1) or any combination or ratio of these cytokines.
      Analysis of 26 supernatants from NC and RRMS patients failed to detect IgM. There
      were very low levels of IgG in 8 of the 26 supernatants, and no correlation
      between of OL death and presence or absence of IgG. Sera used in both the B cell
      and glial cell cultures were heated, which inactivates complement. The effects of
      B cell supernatants on OL could be direct and/or indirect involving either
      microglia and/or astrocytes. The identity of the toxic factor(s) is as yet
      unknown. Thus we have demonstrated that B cells from patients with RRMS but not
      NC secrete one or more factors toxic to OL. It is possible that such factors
      produced by peripheral blood B cells when within the CNS could contribute to
      demyelination in MS patients.

PMID- 22458984
TI  - Cholinergic abnormalities, endosomal alterations and up-regulation of nerve
      growth factor signaling in Niemann-Pick type C disease.
AB  - BACKGROUND: Neurotrophins and their receptors regulate several aspects of the
      developing and mature nervous system, including neuronal morphology and survival.
      Neurotrophin receptors are active in signaling endosomes, which are organelles
      that propagate neurotrophin signaling along neuronal processes. Defects in the
      Npc1 gene are associated with the accumulation of cholesterol and lipids in late
      endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C
      (NPC) disease. The aim of this work was to assess whether the endosomal and
      lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As
      models, we used i) NPC1-deficient mice to evaluate the central cholinergic septo
      hippocampal pathway and its response to nerve growth factor (NGF) after axotomy
      and ii) PC12 cells treated with U18666A, a pharmacological cellular model of NPC,
      stimulated with NGF. RESULTS: NPC1-deficient cholinergic cells respond to NGF
      after axotomy and exhibit increased levels of choline acetyl transferase (ChAT),
      whose gene is under the control of NGF signaling, compared to wild type
      cholinergic neurons. This finding was correlated with increased ChAT and
      phosphorylated Akt in basal forebrain homogenates. In addition, we found that
      cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology,
      suggesting early signs of neurodegeneration. Consistently, PC12 cells treated
      with U18666A presented a clear NPC cellular phenotype with a prominent endocytic
      dysfunction that includes an increased size of TrkA-containing endosomes and
      reduced recycling of the receptor. This result correlates with increased
      sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC
      gamma signaling pathways, increased neurite extension, increased phosphorylation
      of tau protein and cell death when PC12 cells are differentiated and treated with
      U18666A. CONCLUSIONS: Our results suggest that the NPC cellular phenotype causes
      neuronal dysfunction through the abnormal up-regulation of survival pathways,
      which causes the perturbation of signaling cascades and anomalous phosphorylation
      of the cytoskeleton.

PMID- 22458985
TI  - Expression of the phosphorylated MEK5 protein is associated with TNM staging of
      colorectal cancer.
AB  - BACKGROUND: Activation of MEK5 in many cancers is associated with carcinogenesis
      through aberrant cell proliferation. In this study, we determined the level of
      phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues
      and correlated it with clinicopathologic data. METHODS: pMEK5 expression was
      examined by immunohistochemistry in a tissue microarray (TMA) containing 335
      clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal
      tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with
      normal mucosa was examined by Western blotting. The relationship between pMEK5
      expression in CRC and clinicopathologic parameters, and the association of pMEK5
      expression with CRC survival were analyzed respectively. RESULTS: pMEK5
      expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than
      in normal tissues (6 out of 80, 7.5%; P < 0.001). Western blotting demonstrated
      that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to
      the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5
      in CRC tissues was significantly correlated to the depth of invasion (P = 0.001),
      lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and high
      preoperative CEA level (P < 0.001). Consistently, the pMEK5 level in CRC tissues
      was increased following stage progression of the disease (P < 0.001). Analysis of
      the survival curves showed a significantly worse 5-year disease-free (P = 0.002)
      and 5-year overall survival rate (P < 0.001) for patients whose tumors
      overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an
      independent prognostic factor for CRC (DFS: P = 0.139; OS: P = 0.071).
      CONCLUSIONS: pMEK5 expression is correlated with the staging of CRC and its
      expression might be helpful to the TNM staging system of CRC.

PMID- 22458986
TI  - High preoperative depression, phobic anxiety, and binge eating scores and low
      medium-term weight loss in sleeve gastrectomy obese patients: a preliminary
      cohort study.
AB  - OBJECTIVE: Although depression, anxiety, and binge eating are prevalent in
      candidates for bariatric surgery, their impact on weight loss is unknown
      following sleeve gastrectomy. This study assesses the associations between weight
      loss and preoperative depression, anxiety, and binge eating scores in patients
      undergoing sleeve gastrectomy for morbid obesity. METHOD: This cohort study
      included 34 patients who underwent sleeve gastrectomy for morbid obesity between
      May 2006 and February 2010 in a French tertiary referral center. We assessed
      preoperative depression (using the Beck depression inventory and the SCL-90-R
      depression subscale), anxiety (using the Hamilton anxiety rating scale and the
      SCL-90-R anxiety subscales), and binge eating (using the bulimic investigatory
      test, Edinburgh). The primary outcome was the percentage of excess weight loss at
      12 months (PEWL). RESULTS: The preoperative mean body mass index (BMI) was 55.3
      kg/m2 +/- 10.2 kg/m2 and 41.7 kg/m2 +/- 8.7 kg/m2 at the 12-month follow-up
      visit. The mean PEWL was 46.8% +/- 15.8%. After adjusting for the preoperative
      BMI, the PEWL was negatively associated with preoperative scores for depression
      (beta= -0.357; P < 0.05), phobic anxiety (beta = -0.340; P < 0.05), interpersonal
      sensitivity (beta = -0.328; P < 0.05), and binge eating (beta = -0.315; P =
      0.05). Other forms of anxiety were not correlated with the PEWL. CONCLUSIONS:
      Higher preoperative depression, phobic anxiety, interpersonal sensitivity, and
      binge eating scores are associated with low postoperative weight loss in patients
      undergoing sleeve gastrectomy. Future studies should assess the preoperative
      prevalence of syndromal or subsyndromal atypical depression and its relationship
      to postoperative weight loss in bariatric surgery candidates.

PMID- 22458988
TI  - Delayed diagnosis of sporadic Creutzfeldt-Jakob disease in a patient with
      schizophrenia.

PMID- 22458987
TI  - Depressive symptom deterioration among predominantly Hispanic diabetes patients
      in safety net care.
AB  - OBJECTIVE: This study examines clinical predictors of symptom deterioration
      (relapse/recurrence) at the completion of a clinical intervention trial of
      depressed, low-income, predominantly Hispanic diabetes patients who were
      randomized to socio-culturally adapted collaborative depression treatment or
      usual care and who no longer met clinically significant depression criteria at 12
      months post-trial baseline. METHODS: A sub-cohort of 193 diabetes patients with
      major depression symptoms at baseline, who were randomized to a 12-month
      collaborative care intervention (INT) (problem-solving therapy and/or
      pharmacotherapy, telephone symptom monitoring/relapse prevention, behavioral
      activation and patient navigation support) or enhanced usual care (EUC), and who
      did not meet major depression criteria at 12 months were subsequently observed
      over 18 to 24 months. RESULTS: Post-trial depression symptom deterioration was
      similar between INT (35.2%) and EUC (35.3%) groups. Among the combined groups,
      significant predictors of symptom deterioration were baseline history of previous
      depression and/or dysthymia (odds ratio [OR] = 2.66), 12-month PHQ-9 score (OR =
      1.22), antidepressant treatment receipt during the initial 12-months (OR = 2.38),
      12-month diabetes symptoms (OR = 2.27), and new ICD-9 medical diagnoses in the
      initial 12 months (OR = 1.11) (R2 = 27%; max-rescaled R2 = 37%; likelihood ratio
      test, chi2 = 59.79, df = 5, P < 0.0001). CONCLUSIONS: Among predominantly
      Hispanic diabetes patients in community safety net primary care clinics whose
      depression had improved over 1 year, more than one-third experienced symptom
      deterioration over the following year. A primary care management depression care
      protocol that includes ongoing depression symptom monitoring, antidepressant
      adherence, and diabetes and co-morbid illness monitoring plus depression
      medication adjustment and behavioral activation may reduce and/or effectively
      treat depression symptom deterioration.

PMID- 22458990
TI  - A naturalistic on-off-on trial of dextromethorphan/quinidine for agitation
      associated with cerebellar injury.

PMID- 22458989
TI  - Depressive mood and subsequent cancer diagnosis in patients undergoing a
      colonoscopy.
AB  - BACKGROUND: In patients with clinical signs that may indicate a colorectal
      cancer, physicians may interpret the presence of a comorbid depressive mood as
      either increasing or decreasing the likelihood of cancer diagnosis. This study
      examined the association between depressive mood in candidates for a colonoscopy
      and subsequent diagnosis of cancer. METHODS: Ninety-four outpatients [35 men,
      mean age +/- standard deviation (SD) = 56.2 +/- 9.8 years, 59 women, mean age +/-
      SD = 54.2 +/- 12.9 years] were given the 13-item Beck depression inventory to
      assess depressive mood before undergoing a colonoscopy. Additional psychological,
      demographic, and clinical data were collected prior to the colonoscopy. RESULTS:
      The colonoscopy found a cancer in 18 patients (19.1%). Cancer patients were older
      (P = 0.015) and more likely to present with anemia (P < 0.001) and unexplained
      weight loss (P = 0.046). Depressive mood was associated with a subsequent
      diagnosis of cancer in women (P = 0.007), but not in men (P = 0.985). This
      association remained significant after adjustment for potential confounders in
      women (i.e., anemia and unexplained weight loss) (P = 0.014). CONCLUSIONS: In
      women with clinical signs that warrant a colonoscopy, comorbid depressive mood
      may be associated with an increased likelihood of colorectal cancer and should
      not delay the receipt of a guideline-based diagnosis procedure.

PMID- 22458991
TI  - Narcissistic traits and suicide: a case of supportive psychotherapy on a
      psychosomatic medicine service.

PMID- 22458992
TI  - Neuropsychiatric conditions among patients with dyskeratosis congenita: a link
      with telomere biology?
AB  - BACKGROUND: Dyskeratosis congenita (DC), an inherited bone marrow failure
      syndrome (IBMFS), is caused by defects in telomere biology, which result in very
      short germline telomeres. Telomeres, long nucleotide repeats and a protein
      complex at chromosome ends, are essential for chromosomal stability. Several
      association studies suggest that short telomeres are associated with certain
      psychiatric disorders, including mood disorders and schizophrenia. There are two
      cases in the literature of schizophrenia and DC occurring as co-morbid
      conditions. We noted that many patients with DC in our cohort had
      neuropsychiatric conditions. METHODS: Subjects were participants in NCI's IBMFS
      prospective cohort study. Psychiatric evaluation was incorporated into our
      clinical assessment in January 2009. Fourteen DC or DC-like patients, including
      six children, were evaluated in this study through in person interview by either
      a psychiatrist specialized in psychosomatic medicine or a child and adolescent
      psychiatrist. RESULTS: Three of the six pediatric subjects and five of the eight
      adults had a neuropsychiatric condition such as a mood, anxiety, or adjustment
      disorder, intellectual disability, attention deficit hyperactivity disorder, or
      pervasive developmental disorders. The lifetime occurrence of any of these
      disorders in our study was 83% in pediatric subjects and 88% in adults. Notably,
      the literature reports neuropsychiatric conditions in 25% and 38% in chronically
      ill children and adults, respectively. CONCLUSION: This pilot study suggests that
      patients with DC may have higher rates of neuropsychiatric conditions than the
      general population or other chronically ill individuals. This potential link
      between very short telomeres and neuropsychiatric conditions warrants further
      study.

PMID- 22458993
TI  - Psychiatric disorders in Huntington's disease: a 2-year follow-up study.
AB  - OBJECTIVE: This study investigates the presence and course of formal psychiatric
      disorders according to the Diagnostic and Statistical Manual of Mental Disorders,
      4th edition (DSM-IV) in 142 Huntington's disease (HD) mutation carriers in a two
      year follow-up design. METHOD: Of the 142 mutation carriers, 106 (75%)
      participated in the second measurement of an ongoing cohort study on
      psychopathology in HD. Presence of psychiatric disorders was assessed using the
      Composite International Diagnostic Interview. RESULTS: Of the 91 patients without
      a formal psychiatric disorder at baseline, 14 (15%) had a psychiatric disorder
      after 2 years, mostly a major depressive disorder (MDD) (64%). The baseline
      characteristics of lower education, having no children, a lower level of global
      daily functioning, a lifetime psychiatric diagnosis, and the use of psychotropic
      medication were predictive of incident psychiatric disorders after 2 years. Of
      the 15 patients with a psychiatric diagnosis at baseline, eight (53%) no longer
      had a psychiatric disorder at follow-up. All seven patients (47%) with a
      persistent psychiatric disorder were female and their most prevalent diagnosis
      was generalized anxiety disorder. CONCLUSION: This cohort study confirms that
      psychiatric disorders, in particular MDD, frequently occur in patients with HD.
      Professionals working with HD patients should therefore be aware of the high risk
      of psychopathology in HD because early diagnosis and treatment of psychiatric
      disorders may improve the quality of life of patients and their caregivers.

PMID- 22458994
TI  - Delusional infestation is typically comorbid with other psychiatric diagnoses:
      review of 54 patients receiving psychiatric evaluation at Mayo Clinic.
AB  - OBJECTIVE: Delusional infestation, which encompasses both delusions of
      parasitosis and delusions of infestation with inanimate objects (sometimes called
      Morgellons disease), has been said to represent a distinct and encapsulated
      delusion, that is, a stand-alone diagnosis. Anecdotally, we have observed that
      patients with delusional infestation often have one or more psychiatric comorbid
      conditions and that delusional infestation should not be regarded as a stand
      alone diagnosis. The purpose of this study was to identify whether patients with
      delusional infestation have psychiatric comorbid conditions. We therefore
      identified patients who had been formally evaluated in the Department of
      Psychiatry during their visit to Mayo Clinic. METHOD: We retrospectively searched
      for and reviewed the cases of all patients with delusional infestation seen from
      2001 through 2007 at Mayo Clinic, Rochester, Minnesota, and who underwent
      psychiatric evaluation. The diagnoses resulting from psychiatric evaluation were
      analyzed. RESULTS: During the 7-year study period, 109 patients seen for
      delusional infestation at Mayo Clinic were referred to the Department of
      Psychiatry, 54 (50%) of whom actually followed through with psychiatric
      consultation. Of these 54 patients, 40 (74%) received additional active
      psychiatric diagnoses; 14 patients (26%) had delusional infestation alone.
      Abnormal personality traits were rarely documented. CONCLUSIONS: Most patients
      with delusional infestation have multiple coexisting or underlying psychiatric
      disorders. Therefore, evaluation by a psychiatrist, when possible, is advised for
      all patients with delusional infestation.

PMID- 22458995
TI  - The tryptophan depletion theory in delirium: not confirmed in elderly hip
      fracture patients.
AB  - BACKGROUND: The tryptophan depletion theory assumes that low tryptophan levels
      are present in delirium. These lower levels may be regarded as a biochemical
      marker for cellular immune activation, which may lead to increased catabolism of
      tryptophan into kynurenine via stimulation of the enzyme indoleamine 2,3
      dioxygenase (IDO) by interferon-gamma. OBJECTIVE: To compare plasma tryptophan
      and kynurenine levels, and IDO activity in hospitalized patients with and without
      delirium. METHODS: Repeated plasma samples were prospectively collected in hip
      fracture patients, aged 65 years and older. The presence of delirium was assessed
      daily. The associations of a delirious state and tryptophan, kynurenine, and the
      kynurenine/tryptophan ratio measured in samples taken 'before', 'during
      delirium', and 'after delirium' were analyzed with linear mixed models. RESULTS:
      A total of 469 samples from 140 patients were collected. Adjusted for the days on
      which they were drawn, there was no difference for all three measured factors in
      patients with and without delirium, except for an association between a higher
      kynurenine/tryptophan ratio and delirium in a subgroup analysis in preoperative
      samples. CONCLUSIONS: The results do not confirm the previously found lower
      tryptophan levels in delirium on which the tryptophan depletion theory is based.
      However, a preoperative higher kynurenine/tryptophan ratio could be indicative of
      delirium.

PMID- 22458996
TI  - Hepatic dysfunction and survival after orthotopic heart transplantation:
      application of the MELD scoring system for outcome prediction.
AB  - BACKGROUND: The prevalence of heart failure (HF) is rising and the only
      corrective treatment is cardiac transplantation. Advanced HF is associated with
      congestive hepatopathy and progressive functional and ultrastructural changes of
      the liver. We hypothesized that hepatic dysfunction is associated with impaired
      clinical outcome after heart transplantation. METHODS: Data of 617 adult patients
      (75% men, mean age 53 +/- 12 years, mean BMI 25 +/- 4, mean ejection fraction 19
      +/- 9%) undergoing orthotopic heart transplantation (OHT) were analyzed
      retrospectively. Deviation from institutional normal ranges was used to define
      abnormal liver function. Standard Model for End-stage Liver Disease (MELD) scores
      were calculated and a modified MELD score with albumin replacing INR (modMELD)
      was created to eliminate the confounding effects of anti-coagulation. RESULTS:
      Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the
      population, respectively. Total protein and albumin were decreased in 25% and 52%
      of the population, respectively. By 2 months post-transplantation, percentages of
      individuals with pathologic values decreased significantly, except for ALT, total
      protein and albumin, all of which took longer to normalize. Individuals with a
      higher pre-transplantation MELD or modMELD score had worse outcome 30 days post
      transplant and reduced long-term survival over a 10-year follow-up. CONCLUSIONS:
      In this large, single-center retrospective study, we demonstrated the dynamics of
      liver dysfunction after cardiac transplantation and that elevated MELD scores
      indicating impaired liver function are associated with poor clinical outcome
      after OHT. Thus, pre-operative liver dysfunction has a significant impact on
      survival of patients after cardiac transplantation.

PMID- 22458999
TI  - Reported functional impairments of electrohypersensitive Japanese: A
      questionnaire survey.
AB  - An increasing number of people worldwide complain that they have become
      electromagnetic hypersensitive (EHS). We conducted a questionnaire survey of EHS
      persons in Japan. The aim was to identify electromagnetic fields (EMF) and
      plausible EMF sources that caused their symptoms. Postal questionnaires were
      distributed via a self-help group, and 75 participants (95% women) responded.
      Reported major complaints were "fatigue/tiredness" (85%), "headache",
      "concentration, memory, and thinking" difficulty (81%, respectively). Seventy-two
      per cent used some form of complementary/alternative therapy. The most plausible
      trigger of EHS onset was a mobile phone base station or personal handy-phone
      system (37%). Sixty-five percent experienced health problems to be due to the
      radiation from other passengers' mobile phones in trains or buses, and 12%
      reported that they could not use public transportation at all. Fifty-three
      percent had a job before the onset, but most had lost their work and/or
      experienced a decrease in income. Moreover, 85.3% had to take measures to protect
      themselves from EMF, such as moving to low EMF areas, or buying low EMF electric
      appliances. EHS persons were suffering not only from their symptoms, but also
      from economical and social problems.

PMID- 22458997
TI  - Liver dysfunction as a predictor of outcomes in patients with advanced heart
      failure requiring ventricular assist device support: Use of the Model of End
      stage Liver Disease (MELD) and MELD eXcluding INR (MELD-XI) scoring system.
AB  - BACKGROUND: Liver dysfunction increases post-surgical morbidity and mortality.
      The Model of End-stage Liver Disease (MELD) estimates liver function but can be
      inaccurate in patients receiving oral anti-coagulation. We evaluated the effect
      of liver dysfunction on outcomes after ventricular assist device (VAD)
      implantation and the dynamic changes in liver dysfunction that occur during VAD
      support. METHODS: We retrospectively analyzed 255 patients (147 with pulsatile
      devices and 108 with continuous-flow devices) who received a long-term VAD
      between 2000 and 2010. Liver dysfunction was estimated by MELD and MELD-eXcluding
      INR (MELD-XI), with patients grouped by a score of >= 17 or < 17. Primary
      outcomes were on-VAD, after transplant, and overall survival. RESULTS: MELD and
      MELD-XI correlated highly (R >= 0.901, p < 0.0001) in patients not on oral anti
      coagulation. Patients with MELD or MELD-XI < 17 had improved on-VAD and overall
      survival (p < 0.05) with a higher predictive power for MELD-XI. During VAD
      support, cholestasis initially worsened but eventually improved. Patients with
      pre-VAD liver dysfunction who survived to transplant had lower post-transplant
      survival (p = 0.0193). However, if MELD-XI normalized during VAD support, post
      transplant survival improved and was similar to that of patients with low MELD-XI
      scores. CONCLUSIONS: MELD-XI is a viable alternative for assessing liver
      dysfunction in heart failure patients on oral anti-coagulation. Liver dysfunction
      is associated with worse survival. However, if MELD-XI improves during VAD
      support, post-transplant survival is similar to those without prior liver
      dysfunction, suggesting an important prognostic role. We also found evidence of a
      transient cholestatic state after LVAD implantation that deserves further
      examination.

PMID- 22459000
TI  - [Platelet inhibition in acute coronary syndromes: a complex intervention that
      needs optimization].

PMID- 22458998
TI  - Examining the positive effects of exercise in intubated adults in ICU: a
      prospective repeated measures clinical study.
AB  - BACKGROUND: Determining the optimal timing and progression of mobility exercise
      has the potential to affect functional recovery of critically ill adults. This
      study compared standard care with care delivered using a mobility protocol. We
      examined the effects of exercise on vital signs and inflammatory biomarkers and
      the effects of the nurse-initiated mobility protocol on outcomes. METHODS:
      Prospective, repeated measures study with a control (standard care) and
      intervention (protocol) period. RESULTS: 75 heterogeneous subjects admitted to a
      Medical or Surgical intensive care unit (ICU) were enrolled. In <5% of exercise
      periods, there was a concerning alteration in respiratory rate or peripheral
      oxygen saturation; no other adverse events occurred. Findings suggested the use
      of a protocol with one 20 minute episode of exercise daily for 2 or more days
      reduced ICU length of stay. Duration of exercise was linked to increased IL-10,
      suggesting brief episodes of low intensity exercise positively altered
      inflammatory dysregulation in this sample. CONCLUSION: A growing body of evidence
      demonstrates that early, progressive exercise has significant benefits to
      intubated adults. These results should encourage clinicians to add mobility
      protocols to the care of ICU adults and lead to future studies to determine
      optimal "dosing" of exercise in ICU patients.

PMID- 22459001
TI  - Chikungunya virus as a causative agent of fever of unknown origin in Finnish
      travellers to tropics.

PMID- 22459002
TI  - Laboratory diagnosis, molecular characteristics, epidemiological and clinical
      features of an outbreak of measles in a low incidence population in Australia.
AB  - BACKGROUND: Prompt and accurate laboratory diagnosis of measles is essential for
      case detection, outbreak management and ongoing surveillance in low incidence
      countries. Several disease markers are employed for diagnosis and are important
      to determine epidemiological and molecular characteristics for future control
      measures. OBJECTIVES: To report different disease markers, genotypes and
      epidemiology of a measles outbreak in Australia, a low incidence country. STUDY
      DESIGN: A retrospective descriptive study of the clinical and epidemiological
      features and laboratory diagnosis in 16 confirmed measles cases using measles
      serum IgM/IgG, antigen detection (IFA), viral RNA detection by real-time PCR and
      genotyping results for respiratory and urine specimens processed in one reference
      laboratory. RESULTS: Of the 16 confirmed measles cases, 11 were young adults aged
      between 20-35 years and 15 were not age-appropriately vaccinated. The most common
      genotype detected was D9 (11/16), followed by D4 (1/16) and D8 (1/16). Two
      imported cases were from the Philippines (D4) and Italy (D9). Of six disease
      markers, respiratory swab PCR and serum IgM gave the highest percentage (100%) of
      positive samples for confirmed cases followed by urine PCR (90.9%), serum PCR
      (66.6%), urine IFA (54.5%) and respiratory IFA (46.2%). CONCLUSIONS: Measles
      should be considered in the differential diagnosis of a presentation with fever
      and rash, even in countries in the elimination phase of measles control.
      Genotyping is a powerful molecular-epidemiological tool to assist low incidence
      countries towards eradication goals. Improving vaccination coverage remains
      essential, particularly in young adults and travellers.

PMID- 22459003
TI  - Cytomegalovirus-specific T-cell immunity to assign the infection status in
      individuals with passive immunity: a proof of principle.
AB  - BACKGROUND: Serological analysis of the infection status with the human
      cytomegalovirus (CMV) may be inaccurate after transfusion of blood products due
      to the variable content of CMV-specific antibodies. OBJECTIVES: In this
      situation, analysis of cellular immunity may represent a more accurate parameter
      to assign the individual CMV-infection status. This hypothesis was assessed in a
      sequence of clinically defined events where a CMV-seronegative patient received
      human immunoglobulins before AB0 incompatible transplantation of a graft from his
      CMV-seropositive mother and developed CMV-primary infection thereafter. STUDY
      DESIGN: Humoral immunity was analyzed using ELISA, and CMV-specific CD4 T-cells
      were flow-cytometrically quantified using intracellular cytokine staining after a
      6 h-stimulation with a CMV-antigen lysate. RESULTS: Prior to transplantation,
      both CMV-specific antibody-titers and T-cell frequencies were below detection
      limit. After plasma infusion, the patient was temporarily seropositive but
      remained T-cell negative indicating passive immunity. CMV-specific T-cells became
      stably detectable after graft-related primary infection, thereby confirming a
      truly positive infection status. CONCLUSION: This case provides an instructive
      proof of principle to show that CMV-specific CD4 T-cells may serve as an accurate
      marker to define the true CMV-infection status in situations where serological
      testing is limited by the presence of passively administered antibodies.

PMID- 22459004
TI  - Hepatitis C virus genotype distribution varies by underlying disease status among
      patients in the same geographic region: a retrospective multicenter study.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a known carcinogen with considerable
      genetic heterogeneity: six different genotypes have been identified. HCV genotype
      distribution varies from country to country. In the United States, the most
      prevalent genotypes are 1a, and 1b followed by genotypes 2, and 3. OBJECTIVES: To
      examine whether the distribution of HCV genotypes differed by cancer status among
      patients in the same area. STUDY DESIGN: We reviewed epidemiologic and
      virological data of 636 patients with HCV infection evaluated at 3 institutions
      in Houston, Texas, in 2008 and 2009. RESULTS: We included 129 cancer patients (53
      with hematologic malignancies and 76 with solid tumors), 333 immunocompetent
      patients, and 102 HIV-co-infected patients. The prevalence of genotype 1 (G-1)
      was 66% among cancer patients, 84% among immunocompetents (P=0.00004), and 99%
      among HIV-co-infected patients (P<0.00001). G-2 and G-3 were more common in
      cancer patients than other patients. Demographics, risk factors, and duration of
      HCV infection were similar between cancer and immunocompetent patients. G-1 was
      more prevalent in immunocompetents (84%) than in patients with hepatocellular
      carcinoma (74%, P=0.08) or lymphoma (59%, P=0.001). G-2 was more prevalent in
      lymphoma patients (24%) than in immunocompetents (8%, P=0.003); cancer risk was 3
      times as great with G-2 as with other genotypes (OR 3.72, 95% CI 1.38-9.76).
      CONCLUSIONS: This multicenter retrospective study provides evidence of
      differences in HCV genotype distribution by underlying disease among
      geographically related patients and suggests a possible greater carcinogenic
      potential of some variants. Large-scale prospective studies are warranted to
      investigate HCV genotype distribution in other regions.

PMID- 22459005
TI  - Lipid lowering with dietary supplements: focus on diabetes.
AB  - Cardiovascular disease (CVD) is the predominant cause of mortality in type 2
      diabetic (T2DM) patients. Dyslipidemia is a modifiable risk factor that should be
      treated early for CVD prevention. Further, dietary supplement intake is
      increasing in popularity worldwide. This review examines the recent meta-analyses
      and clinical studies on dietary supplements, specifically psyllium, garlic and
      green tea, on plasma lipids levels and glycemic control, as well as other
      potential CVD risk factors in T2DM patients. Generally, results demonstrate that
      psyllium supplements improve lipid profiles as well as glycemic control beyond a
      traditional diet in patients with T2DM. On the other hand, the results on the
      usefulness of garlic and green tea supplementation for dyslipidemia and
      hyperglycemia are uncertain. Overall, the addition of dietary supplements may be
      a therapeutic alternative to lower CVD risk factors in T2DM; however, more well
      designed intervention studies are needed to assess the benefit of these dietary
      supplements.

PMID- 22459006
TI  - Developmental framework to validate future designs of ballistic neck protection.
AB  - The number of neck injuries has increased during the war in Afghanistan, and they
      have become an appreciable source of mortality and long-term morbidity for UK
      servicemen. A three-dimensional numerical model of the neck is necessary to allow
      simulation of penetrating injury from explosive fragments so that the design of
      body armour can be optimal, and a framework is required to validate and describe
      the individual components of this program. An interdisciplinary consensus group
      consisting of military maxillofacial surgeons, and biomedical, physical, and
      material scientists was convened to generate the components of the framework, and
      as a result it incorporates the following components: analysis of deaths and long
      term morbidity, assessment of critical cervical structures for incorporation into
      the model, characterisation of explosive fragments, evaluation of the material of
      which the body armour is made, and mapping of the entry sites of fragments. The
      resulting numerical model will simulate the wound tract produced by fragments of
      differing masses and velocities, and illustrate the effects of temporary cavities
      on cervical neurovascular structures. Using this framework, a new shirt to be
      worn under body armour that incorporates ballistic cervical protection has been
      developed for use in Afghanistan. New designs of the collar validated by human
      factors and assessment of coverage are currently being incorporated into early
      versions of the numerical model. The aim of this paper is to describe this
      developmental framework and provide an update on the current progress of its
      individual components.

PMID- 22459007
TI  - Infantile and acquired nystagmus in childhood.
AB  - Nystagmus is an involuntary, periodic eye movement caused by a slow drift of
      fixation which is followed by a fast refixation saccade (jerk nystagmus) or a
      slow movement back to fixation (pendular nystagmus). In childhood most cases are
      benign forms of nystagmus: idiopathic infantile, ocular or latent nystagmus. They
      arise at the age of 3 months, without oscillopsia and show the absence of the
      physiologic opto-kinetic nystagmus. A full ophthalmologic evaluation is all that
      is needed in most cases: albinism, macular or optic nerve hypoplasia and
      congenital retinal dystrophies are the most common forms of ocular nystagmus.
      Idiopathic infantile nystagmus can be hereditary, the most common and best
      analyzed form being a mutation of the FRMD7 gene on chromosome Xq26.2. The
      mutation shows a mild genotype-phenotype correlation. In all female carriers the
      opto-kinetic nystagmus is absent and half had mild nystagmus. Latent nystagmus is
      part of the infantile esotropia syndrome and shows the unique feature of change
      of direction when the fixing eye changes: it is always beating to the side of the
      fixing eye. There is no cure for infantile nystagmus but therapeutic options
      include magnifying visual aids or eye muscle surgery at the age of 6-8 y in
      patients with head turn. Less than 20% of childhood nystagmus are acquired and
      need further neurological and imaging work-up. Alarming signs and symptoms are:
      onset after the age of 4 months, oscillopsia, dissociated (asymmetric) nystagmus,
      preserved opto-kinetic nystagmus, afferent pupillary defect, papilloedema and
      neurological symptoms like vertigo and nausea. The most common cause is due to
      pathology of the anterior optic pathway (e.g. optic nerve gliomas). It shows the
      same clinical feature of dissociated nystagmus as spasmus nutans but has a higher
      frequency as in INO. Other forms of acquired nystagmus are due to brainstem,
      cerebellar or metabolic diseases.

PMID- 22459008
TI  - Developing a measure of local agency adaptation to emergencies: a metric.
AB  - Local public health agencies often must respond to health-related emergencies or
      disasters, while continuing to fulfill all public health functions for which they
      are funded. This article reports the development and initial pilot test of a
      method for measuring the nature and degree of a public health agency's response
      to such an emergency or disaster. How the instrument was developed as well as the
      initial results from the pilot study of four local public health systems (LPHSs)
      are presented and discussed. The instrument measured the extent to which each
      function and division of each of the four LPHSs were affected and provided a
      metric that could be used across LPHSs to indicate the burden experienced by each
      due to the emergency. Results obtained from the pilot study indicate that size
      and complexity of an LPHS was not predictive of its ability to respond to the
      emergency. These results support the use of the framework and associated
      measurement procedures to provide valuable information to managers responsible
      for such LPHSs. Such information should provide a foundation for comparing
      variations in performance and outcomes to various types of emergencies that vary
      in their severity and focus.

PMID- 22459009
TI  - Mentoring, educational services, and incentives to learn: what do we know about
      them?
AB  - This paper reviews recent studies on the effectiveness of services and incentives
      offered to disadvantaged youths both in the US and abroad. We focus our analysis
      on three types of interventions: mentoring, educational services, and financial
      rewards. The objective of this article is threefold. First, we explain
      alternative theoretical points of view in favor (or against-when applicable) each
      of these interventions. We then discuss how recent empirical work has affected
      that view and summarize the latest findings. We conclude by considering which
      questions remain to be examined. Our hope is that this article will serve as a
      resource for those seeking to understand which educational interventions work and
      for whom, and to be used as a starting point for the debate on where to go next.

PMID- 22459010
TI  - Escape mutants of pandemic influenza A/H1N1 2009 virus: variations in antigenic
      specificity and receptor affinity of the hemagglutinin.
AB  - A panel of 6 neutralizing monoclonal antibodies (MAbs) raised against
      A/Moscow/IIV01/2009 (H1N1) virus isolated during the 2009 pandemic was used for
      the selection of 26 escape mutants. The mutants were characterized in immune
      cross-reactions with the panel of MAbs. The sequencing of the mutant HA genes
      revealed 5 amino acid positions recognized by monoclonal antibodies: 129, 156,
      158, 159, and 190 (H3 numbering). The amino acid positions were distributed in
      two epitopes belonging to antigenic sites Sa and Sb. The mutant HAs exhibited
      variations in the affinity to synthetic high molecular mass sialic acid
      containing receptor analogues. Results are discussed in connection with the
      antigenic drift potential of the "swine-like" pandemic 2009 influenza virus.

PMID- 22459011
TI  - The effect of an educational intervention on junior doctors' knowledge and
      practice in detecting and managing elder abuse.
AB  - BACKGROUND: Elder abuse is often unreported, undetected, and underestimated by
      professionals. For the first time, we report the effectiveness of an educational
      elder abuse intervention over three months and its impact on professionals'
      practice. METHODS: Forty trainee psychiatrists in two London National Health
      Service trusts completed the KAMA (Knowledge and Management of Elder Abuse) and
      CSQ (Caregiver Scenario Questionnaire) measuring knowledge about managing and
      detecting elder abuse, before and immediately after a brief group education
      session. We asked how often they considered, asked about, detected, and managed
      elder abuse and their confidence in doing so, at baseline and three months post
      intervention. RESULTS: Compared with baseline, participants scored higher on the
      KAMA (paired t = 3.4, p = 0.002), and identified more definitely abusive (t =
      3.0, p = 0.003) and possibly abusive (t = 2.1, p = 0.043) items immediately post
      intervention. At three-month follow up, 24 (60%) participants reported higher
      confidence in managing abuse (Wilcoxon signed ranks test z = 3.7, p < 0.001) and
      considered it more frequently (z = 2.8, p = 0.006), but did not ask older people
      and their carers about abuse more frequently (z = 1.2, p = 0.24). Two (5%, 95%
      confidence interval 2%-17%) participants detected abuse in the three months
      before the intervention, compared with 2 (8%, 2%-26%) in the same period
      afterward. CONCLUSIONS: This brief educational intervention increased trainee
      psychiatrists' knowledge and vigilance for abuse immediately and after three
      months. They remained reluctant to ask about abuse for reasons including fear of
      causing offence or harming the therapeutic relationship and being unsure how to
      ask people with dementia. We postulate that changing doctors' behavior may
      require a more complex intervention, focusing on communication skills.

PMID- 22459012
TI  - Towards advanced aqueous dye removal processes: a short review on the versatile
      role of activated carbon.
AB  - During the last decade, several physico-chemical and biological techniques have
      been developed to remove colour from textile wastewaters. Some of these
      techniques rely on and many will profit from activated carbon (AC). The role of
      AC is versatile: (1) it acts as a dye adsorbent, not only in straightforward
      adsorption processes but also in AC-enhanced coagulation and membrane filtration
      processes; (2) it generates strong oxidising agents (mostly, hydroxyl (OH)
      radicals) in electrochemical dye oxidation; (3) it catalyses OH production in
      advanced oxidation processes; (4) it catalyses anaerobic (azo) dye reduction and
      supports biofilm growth in microbial dye removal. This paper reviews the role of
      AC in dye decolourisation, evaluates the feasibility of each AC-amended
      decolourisation technique and discusses perspectives on future research.

PMID- 22459013
TI  - Sorption of norfloxacin onto humic acid extracted from weathered coal.
AB  - Norfloxacin (NOR), is an ionizable and polar antimicrobial compound, and it may
      enter the environment in substantial amounts via the application of manure or
      sewage as a fertilizer. Sorption of NOR onto humic acid (HA) may affect its
      environmental fate. In this study, HA extracted from weathered coal was used to
      investigate the sorption of NOR at different solution chemistry conditions (pH,
      ionic strength) and temperatures. The sorption of NOR onto HA showed a two-stage
      sorption process with an equilibration time of 48 h. The sorption kinetic curve
      fitted well with a pseudo second-order kinetic model. Thermodynamic
      characteristics demonstrated that the sorption of NOR onto HA was a spontaneous
      and exothermic process predominated by physical sorption. All sorption isotherms
      fitted well with the Freundlich and Langmuir models and they were highly
      nonlinear with values of n between 0.4 and 0.5, suggesting the high heterogeneity
      of HA. Increasing Ca2+ concentration resulted in a considerable reduction in the
      K(d) values of NOR, hinting that Ca2+ had probably competed with NOR(+,0) for the
      cation exchange sites on the surfaces of HA. The sorption reached a maximum at pH
      6.0 over the pH range of 2.0-8.0, implying that the primary sorption mechanism
      was cation exchange interaction between NOR(+,0) species and the negatively
      charged functional groups of HA. Spectroscopic evidence demonstrated that the
      piperazinyl moiety of NOR was responsible for sorption onto HA, while the
      carbonyl group and the aromatic structure of HA participated in adsorbing NOR.

PMID- 22459014
TI  - Environmental consequences of processing manure to produce mineral fertilizer and
      bio-energy.
AB  - Liquid animal manure and its management contributes to environmental problems
      such as, global warming, acidification, and eutrophication. To address these
      environmental issues and their related costs manure processing technologies were
      developed. The objective here was to assess the environmental consequences of a
      new manure processing technology that separates manure into a solid and liquid
      fraction and de-waters the liquid fraction by means of reverse osmosis. This
      results in a liquid mineral concentrate used as mineral nitrogen and potassium
      fertilizer and a solid fraction used for bio-energy production or as phosphorus
      fertilizer. Five environmental impact categories were quantified using life cycle
      assessment: climate change (CC), terrestrial acidification (TA), marine
      eutrophication (ME), particulate matter formation (PMF), and fossil fuel
      depletion (FFD). For pig as well as dairy cattle manure, we compared a scenario
      with the processing method and a scenario with additional anaerobic digestion of
      the solid fraction to a reference situation applying only liquid manure.
      Comparisons were based on a functional unit of 1 ton liquid manure. System
      boundaries were set from the manure storage under the animal house to the field
      application of all end products. Scenarios with only manure processing increased
      the environmental impact for most impact categories compared to the reference: ME
      did not change, whereas, TA and PMF increased up to 44% as a result of NH3 and
      NO(x) emissions from processing and storage of solid fraction. Including
      digestion reduced CC by 117% for pig manure and 104% for dairy cattle manure,
      mainly because of substituted electricity and avoided N2O emission from storage
      of solid fraction. FFD decreased by 59% for pig manure and increased 19% for
      dairy cattle manure. TA and PMF remained higher compared to the reference.
      Sensitivity analysis showed that CH4 emission from manure storage, NH3 emission
      from processing, and the replaced nitrogen fertilizer by the mineral concentrate
      were important parameters affecting final results. It was concluded that
      processing fattening pig and dairy cattle manure to produce mineral fertilizer
      increased overall environmental consequences in terms of CC (except for dairy
      cattle manure), TA, PMF, and FFD compared to current agricultural practice.
      Adding the production of bio-energy reduced CC and FFD. Only when NH3 emission
      from processing was low and bio-energy was produced, overall equal or better
      environmental performance was obtained for TA and PMF. It was emphasized that
      real time measurements should be done to enhance the environmental assessment of
      manure processing technologies. Results of this study present the full
      environmental consequences of manure processing and key parameters affecting the
      environmental impact of manure management. Outcomes can be used for decision
      making and further tackling of environmental problems related to manure
      management.

PMID- 22459015
TI  - Genotoxicity assessment in Eisenia andrei coelomocytes: a study of the induction
      of DNA damage and micronuclei in earthworms exposed to B[a]P- and TCDD-spiked
      soils.
AB  - Earthworms are useful indicators of soil quality and are widely used as model
      organisms in terrestrial ecotoxicology. The assessment of genotoxic effects
      caused by environmental pollutants is of great concern because of their relevance
      in carcinogenesis. In this work, the earthworm Eisenia andrei was exposed for 10
      and 28 days to artificial standard soil contaminated with environmentally
      relevant concentrations of benzo[a]pyrene (B[a]P) (0.1, 10, 50ppm) and 2,3,7,8
      tetrachloro-dibenzo-para-dioxin (TCDD) (1*10(-5), 1*10(-4), 2*10(-3)ppm).
      Micronucleus (MNi) induction was evaluated in earthworm coelomocytes after DNA
      staining with the fluorescent dye DAPI. In the same cells, the DNA damage was
      assessed by means of the alkaline comet assay. Induction of MNi in coelomocytes,
      identified according to standard criteria, was demonstrated. B[a]P exposure for
      10 and 28 days induced a significant increase in MNi frequency. In TCDD-treated
      earthworms, a significant effect on chromosomal damage was observed at all the
      concentrations used; surprisingly, greater effects were induced in animals
      exposed to the lowest concentration (1*10(-5)ppm). The data of the comet assay
      revealed a significant increase in the level of DNA damage in coelomocytes of
      earthworms exposed for 10 and 28 days to the different concentrations of B[a]P
      and TCDD. The results show that the comet and MN assays were able to reveal
      genotoxic effects in earthworms exposed even to the lowest concentrations of both
      chemicals tested here. The combined application in E. andrei of the comet assay
      and the micronucleus test, which reflect different biological mechanisms, may be
      suggested to identify genotoxic effects induced in these invertebrates by
      environmental contaminants in terrestrial ecosystems.

PMID- 22459017
TI  - Boosting human learning by hypnosis.
AB  - Human learning and memory depend on multiple cognitive systems related to
      dissociable brain structures. These systems interact not only in cooperative but
      also sometimes competitive ways in optimizing performance. Previous studies
      showed that manipulations reducing the engagement of frontal lobe-mediated
      explicit attentional processes could lead to improved performance in striatum
      related procedural learning. In our study, hypnosis was used as a tool to reduce
      the competition between these 2 systems. We compared learning in hypnosis and in
      the alert state and found that hypnosis boosted striatum-dependent sequence
      learning. Since frontal lobe-dependent processes are primarily affected by
      hypnosis, this finding could be attributed to the disruption of the explicit
      attentional processes. Our result sheds light not only on the competitive nature
      of brain systems in cognitive processes but also could have important
      implications for training and rehabilitation programs, especially for developing
      new methods to improve human learning and memory performance.

PMID- 22459016
TI  - Survival of endometrial cancer patients in Germany in the early 21st century: a
      period analysis by age, histology, and stage.
AB  - BACKGROUND: Population-based studies on endometrial cancer providing survival
      estimates by age, histology, and stage have been sparse. We aimed to derive most
      up-to-date and detailed survival estimates for endometrial cancer patients in
      Germany. METHODS: We used a pooled German national dataset including data from 11
      cancer registries covering a population of 33 million people. 30,906 patients
      diagnosed with endometrial cancer in 1997-2006 were included. Period analysis was
      performed to calculate 5-year relative survival (RS) in 2002-2006. Trends in
      survival between 2002 and 2006 were examined using model-based period analysis.
      Age-adjustment was performed using five age groups (15-44, 45-54, 55-64, 65-74,
      and 75+ years). RESULTS: Overall, age-adjusted 5-year relative survival in 2002
      2006 was 81%. A moderate age gradient was observed, with 5-year RS decreasing
      from 90% in the age group 15-49 years to 75% in the age group 70+ years.
      Furthermore prognosis varied strongly by histologic subtypes and stage, with age
      adjusted 5-year RS ranging from 43% (for sarcoma) to 94% (for squamous
      metaplasia), and reaching 91% for localized, 51% for regional, and 20% for
      distant stage. Except for age group 65-74 years, no significant improvement in
      survival was seen during the recent 5-year period under investigation.
      CONCLUSION: In this comprehensive population-based survival analysis of patients
      with endometrial cancer from Germany, prognosis of endometrial cancer moderately
      varied by age, and strongly varied by histology and stage. While prognosis is
      rather good overall, further improvement in 5-year relative survival of
      endometrial cancer patients has been stagnating in the early 21(st) century.

PMID- 22459018
TI  - Quick recovery of myocardium damage in a case of subacute thyroiditis.
AB  - We describe a case of quick recovery of myocardium damage in a 15-year-old
      adolescent with subacute thyroiditis. After 1 week of admission, his
      cardiovascular status began to show signs of improvement accompanied by the
      recovery of electrocardiogram and indicators of myocardial damage. We speculate
      that myocardium damage associated with subacute thyroiditis is a complication of
      common virus, although we did not detect any abnormal virus antibody and
      deoxyribonucleic acid in the patient's serum.

PMID- 22459019
TI  - Epidemiology and pathophysiology of alcohol and breast cancer: Update 2012.
AB  - AIMS: To update epidemiological data on alcohol and breast cancer, with special
      emphasis on light alcohol consumption, and to review mechanisms of alcohol
      mediated mammary carcinogenesis. METHODS: For epidemiological data, in November
      2011 we performed a literature search in various bibliographic databases, and we
      conducted a meta-analysis of data on light alcohol drinking. Relevant mechanistic
      studies were also reviewed to November 2011. RESULTS: A significant increase of
      the order of 4% in the risk of breast cancer is already present at intakes of up
      to one alcoholic drink/day. Heavy alcohol consumption, defined as three or more
      drinks/day, is associated with an increased risk by 40-50%. This translates into
      up to 5% of breast cancers attributable to alcohol in northern Europe and North
      America for a total of approximately 50,000 alcohol-attributable cases of breast
      cancer worldwide. Up to 1-2% of breast cancers in Europe and North America are
      attributable to light drinking alone, given its larger prevalence in most female
      populations when compared with heavy drinking. Alcohol increases estrogen levels,
      and estrogens may exert its carcinogenic effect on breast tissue either via the
      ER or directly. Other mechanisms may include acetaldehyde, oxidative stress,
      epigenetic changes due to a disturbed methyl transfer and decreased retinoic acid
      concentrations associated with an altered cell cycle. CONCLUSIONS: Women should
      not exceed one drink/day, and women at elevated risk for breast cancer should
      avoid alcohol or consume alcohol occasionally only.

PMID- 22459020
TI  - Dutch and Norwegian support of alcohol policy measures to prevent young people
      from problematic drinking: a cross-national comparison.
AB  - AIMS: To examine whether Dutch and Norwegian adults differ in their opinion on
      policy measures that may prevent young people from problematic drinking. METHODS:
      Data were derived from a web-based cross-sectional study. In this study, only
      Dutch and Norwegian adults (aged >=24 years) were included (n(NL) = 5023, n(NO) =
      1916). Opinions on policy items concerning restrictive and educational measures
      were examined together with alcohol consumption. RESULTS: Differences between the
      opinions of the Dutch and Norwegians concerning the restrictive and educational
      measures were small. In both countries, the support for restrictive measures was
      predicted by female gender, higher age and less own alcohol consumption. For the
      educational measures, the explained variance in the Norwegian and Dutch sample
      was relatively low; this indicates that opinion was more strongly predicted by
      other factors. CONCLUSION: This study indicates that, despite the differences
      between the Dutch and Norwegian alcohol policy, differences in opinion are small
      between Dutch and Norwegian respondents, especially regarding restrictive
      measures that may prevent young people from drinking.

PMID- 22459021
TI  - Relationship of metabolic syndrome and its components with -844 G/A and HindIII
      C/G PAI-1 gene polymorphisms in Mexican children.
AB  - BACKGROUND: Several association studies have shown that -844 G/A and HindIII C/G
      PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin
      resistance, glucose intolerance, hypertension and dyslipidemia, which are
      components of metabolic syndrome. The aim of this study was to analyze the allele
      and genotype frequencies of these polymorphisms in PAI-1 gene and its association
      with metabolic syndrome and its components in a sample of Mexican mestizo
      children. METHODS: This study included 100 children with an age range between 6
      11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome
      and b) 52 children metabolically healthy without any clinical and biochemical
      alteration. Metabolic syndrome was defined as the presence of three or more of
      the following criteria: fasting glucose levels >= 100 mg/dL, triglycerides >= 150
      mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI >= 95th percentile, systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) >= 95th percentile and insulin
      resistance HOMA-IR >= 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were
      analyzed by PCR-RFLP. RESULTS: For the -844 G/A polymorphism, the G/A genotype
      (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015) and the A allele (OR = 2.2; 95% CI,
      1.10-4.43; p = 0.015) were associated with metabolic syndrome. The -844 G/A and
      A/A genotypes were associated with increase in plasma triglycerides levels (OR =
      2.6; 95% CI, 1.16 to 6.04; p = 0.02), decrease in plasma HDL-cholesterol levels
      (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03) and obesity (OR = 2.6; 95% CI, 1.17
      5.92; p = 0.01). The C/G and G/G genotypes of the HindIII C/G polymorphism
      contributed to a significant increase in plasma total cholesterol levels (179 vs.
      165 mg/dL; p = 0.02) in comparison with C/C genotype. CONCLUSIONS: The -844 G/A
      PAI-1 polymorphism is related with the risk of developing metabolic syndrome,
      obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was
      associated with the increase of total cholesterol levels in Mexican children.

PMID- 22459022
TI  - Neuropsychological outcome from blast versus non-blast: mild traumatic brain
      injury in U.S. military service members.
AB  - The purpose of this study was to compare the neuropsychological outcome from
      blast-related versus non-blast related mild traumatic brain injury (MTBI).
      Participants were 56 U.S. military service members who sustained an MTBI, divided
      into two groups based on mechanism of injury: (a) non-blast related (Non-blast; n
      = 21), and (b) blast plus secondary blunt trauma (Blast Plus; n = 35). All
      participants had sustained their injury in theatre whilst deployed during
      Operation Iraqi Freedom or Operation Enduring Freedom. Patients had been seen for
      neuropsychological evaluation at Walter Reed Army Medical Center on average 4.4
      months (SD = 4.1) post-injury. Measures included 14 clinical scales from the
      Personality Assessment Inventory (PAI) and 12 common neurocognitive measures. For
      the PAI, there were no significant differences between groups on all scales (p >
      .05). However, medium effect sizes were found for the Depression (d = .49) and
      Stress (d = .47) scales (i.e., Blast Plus > Non-blast). On the neurocognitive
      measures, after controlling for the influence of psychological distress (i.e.,
      Depression, Stress), there were no differences between the Non-blast and Blast
      Plus groups on all measures. These findings provide little evidence to suggest
      that blast exposure plus secondary blunt trauma results in worse cognitive or
      psychological recovery than blunt trauma alone. (JINS, 2012, 18, 595-605).

PMID- 22459023
TI  - Synthesis of colloidal dispersions of NiAl, ZnAl, NiCr, ZnCr, NiFe, and MgFe
      hydrotalcite-like nanoparticles.
AB  - Colloidal aqueous dispersions of nanometric NiAl, ZnAl, NiCr, ZnCr, NiFe, and
      MgFe hydrotalcite-like compounds were prepared in a water/cetyltrimethylammonium
      bromide/n-butanol/isooctane microemulsion. Particle sizes were analyzed with
      different techniques, and the results confirm dimensions between 10 and 30 nm,
      except for ZnAl-HTlc (150-200 nm). A good colloidal stability of HTlc-NPs aqueous
      dispersions, investigated with DLS and Pz measurements, was obtained without the
      need for any stabilizing agent. SEM images clearly showed that the obtained HTlc
      posses a high tendency to spontaneously form homogeneous and dense stacking of
      plate-like HTlc crystals directly from aqueous solution, giving rise to the
      developing of functional materials in optical, electrical and magnetic fields.

PMID- 22459024
TI  - Competitive ligand exchange on akaganeite surfaces enriches bulk chloride
      loadings.
AB  - Akaganeite (beta-FeOOH) is a nanosized iron oxyhydroxide mineral with a
      hollandite structure containing chloride ions in 0.4 * 0.4 nm wide channels.
      Proton and chloride co-sorption into these channels induces variations in bulk O
      H stretching vibrations, crystallographic lattice size, and thermal stability, as
      a result of hydrogen bond formation with chloride ions. In this work, we show
      that chloride ions bound to akaganeite surfaces can be dislodged into aqueous
      solutions by competitive adsorption of foreign ions and then transferred
      alongside co-sorbed protons into the akaganeite bulk. Fourier transform infrared
      and X-ray photoelectron spectroscopic measurements show that HClO(4), H(2)SO(4),
      and benzoic acid, and thereby, many other anions of various charge-to-size ratios
      can all effectively contribute to this phenomenon. This linked surface-bulk
      reactivity should be accounted for in mixed anion systems containing akaganeite
      like materials.

PMID- 22459025
TI  - Enhanced adsorption of paracetamol on closed carbon nanotubes by formation of
      nanoaggregates: carbon nanotubes as potential materials in hot-melt drug
      deposition-experiment and simulation.
AB  - We present the new results of systematic studies of paracetamol adsorption on
      closed, commercially available, unmodified carbon nanotubes. The results of
      thermal analysis, static adsorption measurements and the comparison with phenol
      adsorption data lead to suggestion that the formation of paracetamol
      nanoaggregates in the interstitial spaces between nanotubes occurs. This effect
      is also confirmed by the results of (performed in two ways) independent dynamic
      measurements and by molecular dynamics simulation technique. Next, we show that
      the behavior of adsorbed paracetamol during heating leads to the creation of a
      new drug delivery system. The properties of this system depend on the type of
      applied nanotubes and the parameters of the process called hot-melt drug
      deposition. Thus, we conclude that confined nanoaggregate formation, as well as
      hot-melt deposition should be promising effects in the preparation of highly
      effective, new drug delivery systems.

PMID- 22459026
TI  - Effects of UV irradiation on the wettability of chitosan films containing dansyl
      derivatives.
AB  - The morphological and wetting properties of chitosan films containing dansyl
      derivatives have been investigated. By means of dynamic contact angle
      measurements, we study the modification of surface properties of chitosan-based
      films due to UV irradiation. The results were analyzed in the light of the
      molecular-kinetic theory which describes the wetting phenomena in terms of the
      statistical dynamics for the displacement of liquid molecules in a solid
      substrate. Our results show that the immobilization of dansyl groups in the
      chitosan backbone leads to a pronounced enhancement of the UV sensitivity of
      polymeric films.

PMID- 22459027
TI  - A cinnamic acid-type photo-cleavable surfactant.
AB  - We have developed a novel cinnamic acid-type photo-cleavable surfactant. This
      surfactant experiences photo-cleavage through UV-induced cyclization in aqueous
      solutions. The photo-cleavage not only reduces its capabilities as a surfactant
      but also yields two functional materials including a coumarin derivative and an
      aminated polyoxyethylene compound. This means that the photo-cleavable surfactant
      synthesized in this study is a photo-responsive function-exchangeable material.
      In our current study, we have characterized the photo-cleavable behavior that
      occurs in aqueous solutions and a resulting change in interfacial properties. The
      photo-cleavage induces an increased interfacial tension of a squalane/water
      interface and a decreased solubilization capability of the surfactant micelles.

PMID- 22459028
TI  - Surface and biological activity of sophorolipid molecules produced by
      Wickerhamiella domercqiae var. sophorolipid CGMCC 1576.
AB  - This work investigated the surface and biological activity of lactonic and acidic
      sophorolipid (SL) molecules differing in the acetylation degree of sophorose,
      carbon chain length and unsaturation degree of the fatty acid moiety. Six
      different SL molecules were prepared from crude SLs produced by Wickerhamiella
      domercqiae var. sophorolipid CGMCC 1576. The structures of the selected SL
      molecules were elucidated by MS and GC/MS. The surface properties of SLs
      including critical micelle concentration (CMC), minimum surface tension (Min.
      S.T.) and emulsification capacity to hydrocarbon and vegetable oils were studied,
      and the results demonstrated that SL molecules with different structures
      exhibited quite different surface properties. Cytotoxicities of different SL
      molecules to Chang liver cells determined by the MTT (3-(4,5-dimethythiazol-2-yl)
      2,5-diphenyl tetrazolium bromide) method showed the effect of chemical structure
      of the SLs on their biological activities. Biodegradability of these SL molecules
      was tested using the river-water die-away method. The differences of surface and
      biological activity in different SL molecules will be of benefit for the
      applications of these SLs in specific fields such as the detergent, petroleum,
      pharmaceutical and environment industries.

PMID- 22459029
TI  - Facile synthesis and photocatalytic properties of AgAgClTiO2/rectorite composite.
AB  - In this study, we prepared a new visible light induced plasmonic photocatalyst
      AgAgClTiO(2)/rectorite using a facile deposition-photoreduction method. The
      catalysts were characterized using X-ray diffraction (XRD), UV-visible diffused
      reflectance spectra (UV-vis DRS), Raman spectra, high-resolution transmission
      electron microscopy (HRTEM), and X-ray photoelectron spectroscopy (XPS). The as
      prepared AgAgClTiO(2)/rectorite powders exhibited an efficient photocatalytic
      activity for the degradation of acid orange (ARG) and 4-nitrophenol (4-NP) under
      visible light irradiation (lambda>400 nm). Moreover, the mechanism suggested that
      the high photocatalytic activity is due to the charge separation and the surface
      plasmon resonance of metallic Ag particles in the region of visible light. The
      active species measurements suggested that HO() is not the dominant photooxidant.
      Direct hole transfers and O(2)(-) were involved as the active species in the
      photocatalytic reaction.

PMID- 22459030
TI  - Polystyrene nanoparticles doped with a luminescent europium complex.
AB  - Polystyrene nanoparticles doped with a luminescent europium complex,
      Eu(tta)(3)phen, are prepared by miniemulsion polymerization. The influence of the
      complex on the miniemulsion polymerization is investigated by the systematic
      variation of the initial concentration of Eu(tta)(3)phen from 2 to 7 wt%
      relatively to styrene. A maximum doping level of about 2% by weight in the final
      particles can be achieved. At higher doping levels, destabilization of the
      miniemulsion leads to a loss of reproducibility with respect to both the degree
      of conversion and the final Eu content of the particles. Doped nanoparticles of
      varying diameter, ranging from 19 to 94 nm, are successfully prepared. Steady
      state and time-resolved luminescence measurements indicate that the luminescence
      properties of Eu(tta)(3)phen in the doped latexes are unchanged from those found
      in THF solution. Aqueous dispersions of the doped particles exhibit
      characteristic red emission under UV light irradiation. The luminescence
      intensity increases linearly with Eu(tta)(3)phen content, indicating the absence
      of self-quenching despite the relatively high local concentrations within the
      particles.

PMID- 22459031
TI  - Multilayer film assembled from charged derivatives of chitosan: physical
      characteristics and biological responses.
AB  - Polyelectrolyte multilayer films were successfully assembled from each of the
      three charged derivatives of chitosan; N-[(2-hydroxyl-3
      trimethylammonium)propyl]chitosan chloride (HTACC), N-succinyl chitosan (SCC) and
      N-sulfofurfuryl chitosan (SFC), paired with one of the two oppositely charged
      polyelectrolytes, poly(acrylic acid) (PAA) and poly(allylamine hydrochloride)
      (PAH) on surface-treated poly(ethylene terephthalate) (treated PET) substrates by
      alternate layer-by-layer adsorption. Surface coverage and wettability of the
      multilayer films were determined by AFM and water contact angle measurements,
      respectively. Analysis by quartz crystal balance with dissipation (QCM-D) has
      suggested that all multilayer films are relatively rigid and have a high water
      content associated within their structures, accounting for up to 85-90% (w/w) for
      films having 7-10 layers. In vitro cytocompatibility tests for the fibroblast
      like L929 cell line revealed a slight dependency for cell adhesion and
      proliferation on the outermost layer. The multilayer film containing HTACC
      exhibited moderate antibacterial activity against E. coli and S. aureus. Bearing
      negative charges, the multilayer films terminating with SFC and having at least
      10 layers were capable of suppressing the adsorption of plasma proteins and
      platelet adhesion at a comparable level to the multilayer film assembled from
      heparin, a well-known antithrombogenic polymer.

PMID- 22459032
TI  - Photochromic fused-naphthopyrans without residual color.
AB  - A series of new photochromic fused-naphthopyrans with an alkyl bridge between the
      pyran ring and the naphthalenic core was synthesized in several steps from 4
      (bromomethyl)benzocoumarin. The presence of the alkyl bridge in these new fused
      naphthopyrans prevents the formation of one long-lived photoisomer and therefore
      has a dramatic effect on their photochromic properties: UV irradiation of common
      naphthopyrans gives rise to two isomeric colored photoisomers, one of which fades
      very slowly and is responsible for a persistent residual color. UV excitation of
      these new uncolored fused-naphthopyrans leads to the formation of only one
      colored photoisomer that fades completely to the uncolored state in few
      seconds/minutes following a monoexponential decay law, thus avoiding the problem
      of the residual coloration typically observed with naphthopyrans.

PMID- 22459033
TI  - Similarities and differences in aspirated tracheobronchial foreign bodies in
      patients under the age of 3 years.
AB  - OBJECTIVE: To investigate the clinical pathological features of aspirated
      tracheobronchial foreign body (FB) cases in children under the age of 3 years and
      to improve the level of diagnosis and treatment. METHODS: A retrospective study
      was conducted examining 316 children under the age of 3 years who had been
      treated for tracheobronchial FB in Shenzhen children's hospital between January
      2004 and December 2008. We analyzed the patients for gender, age, FB
      localization, treatment history, the history of foreign body aspiration (FBA),
      the type of foreign body and the cause of death. In addition, each patient was
      analyzed for FB-related complication, the results of bronchoscopic removal and
      the presence of foreign bodies in the airways. RESULTS: Fifty-two infants under
      the age of one year (median age=10m, group A), 199 children between the ages of 1
      and 2 years (median age=17 m, group B) and 65 children between the ages of 2 and
      3 years (median age=30m, group C) were included in this study. There were 38
      (73.1%) patients with a confirmed history of FBA in group A, a higher percentage
      than that observed in group B (55.8%) or group C (53.8%) (P<0.05). Earthnuts were
      the most common cause of FB (171 cases, 54.1%). Melon seeds (including sunflower
      seeds, watermelon seeds and pumpkin seeds) were the second most common cause of
      FB (62 cases, 19.6%). Animal sources (including 16 pig bones, 8 fish bones, 7
      chicken bones and 4 other animal-based foods) comprised 11.1% (35 cases) of FB
      cases and were the third most common cause of FB. The percentage of animal-based
      FBs observed in group A was higher than in groups B and C (P<0.01). Five
      inorganic FBs (a pushpin, a rubber band, a screw, a small stone and a plastic
      toy) were also observed and were the least common type of FB. There were no
      significant differences in the distribution of FBs between the left (41.8%) and
      right (40.5%) bronchia. There is no difference in the distribution of FBs among
      the three groups either. The data show that the youngest cohort of patients (0-1
      years) is the most likely to be sent to the hospital to receive treatment within
      24h of aspiration (50%) (P<0.01). Five patients (1.58%) died as the result of
      FBA. CONCLUSIONS: FBAs of animal-derived FBs (especially animal bones) are very
      common in infants in southern China. Children between the ages of 1 and 2 years
      are most likely to suffer from FBA. FBA in children under the age of 3 years
      carries significant hazards, including morbidity and mortality. Asphyxia and/or
      cardiopulmonary arrest is prone to occur shortly after FBA in infants, but these
      events can occur days later in older children after FBA because of delays in the
      diagnosis and/or treatment of this condition.

PMID- 22459034
TI  - Predictors of bleeding disorders in children with epistaxis: value of
      preoperative tests and clinical screening.
AB  - OBJECTIVE: To identify prevalence of previously undiagnosed bleeding disorders in
      children with severe epistaxis who failed medical therapy requiring
      intraoperative nasal cautery. STUDY DESIGN: Retrospective chart review 10/15/2006
      12/31/2010. SETTING: Single provider outpatient otolaryngology clinic. SUBJECTS
      AND METHODS:  INCLUSION CRITERIA: children (<19 years) with epistaxis referred to
      otolaryngology, no known bleeding disorder, failed medical therapy and received
      surgical nasal cautery. DATA COLLECTED: duration/severity of epistaxis, bleeding
      history, family history of bleeding. A screening CBC, PT and PTT were performed
      on all patients. RESULTS: Of 248 subjects referred for epistaxis, 47(19%) met
      inclusion criteria (mean age 9.2+/-0.5 years; 61.7% male). 31.9% (15/47) had
      abnormal coagulation studies but on repeat testing only 2 patients had persistent
      coagulation abnormalities. 15 patients were referred to hematology, 5 were
      diagnosed with a bleeding disorder (3 - type 1 von Willebrand's disease, 1 -
      platelet aggregation disorder, 1 - mild factor VII deficiency). Out of the entire
      cohort 10.6% (5/47) had a bleeding diathesis. Clinical predictive factors for
      having a bleeding diathesis were explored and included previous emergency room
      visits for epistaxis (p=0.04). A trend was found in those presenting with
      epistaxis at a younger age (p=0.07). CONCLUSION: Children with recurrent
      epistaxis despite medical therapy are at higher risk of having a bleeding
      disorder. In this highly selected group of patients 10.6% (5/47) were found to
      have a bleeding disorder. Screening coagulation studies (PT, PTT) only revealed
      20% (1/5) of patients with a bleeding disorder. Only a subsequent comprehensive
      hematology evaluation revealed the diagnosis in the majority of patients.

PMID- 22459035
TI  - Predicting social functioning in children with a cochlear implant and in normal
      hearing children: the role of emotion regulation.
AB  - OBJECTIVE: The purpose of the present study was to compare children with a
      cochlear implant and normal hearing children on aspects of emotion regulation
      (emotion expression and coping strategies) and social functioning (social
      competence and externalizing behaviors) and the relation between emotion
      regulation and social functioning. METHODS: Participants were 69 children with
      cochlear implants (CI children) and 67 normal hearing children (NH children) aged
      1.5-5 years. Parents answered questionnaires about their children's language
      skills, social functioning, and emotion regulation. Children also completed
      simple tasks to measure their emotion regulation abilities. RESULTS: Cochlear
      implant children had fewer adequate emotion regulation strategies and were less
      socially competent than normal hearing children. The parents of cochlear implant
      children did not report fewer externalizing behaviors than those of normal
      hearing children. While social competence in normal hearing children was strongly
      related to emotion regulation, cochlear implant children regulated their emotions
      in ways that were unrelated with social competence. On the other hand, emotion
      regulation explained externalizing behaviors better in cochlear implant children
      than in normal hearing children. While better language skills were related to
      higher social competence in both groups, they were related to fewer externalizing
      behaviors only in cochlear implant children. CONCLUSIONS: Our results indicate
      that cochlear implant children have less adequate emotion-regulation strategies
      and less social competence than normal hearing children. Since they received
      their implants relatively recently, they might eventually catch up with their
      hearing peers. Longitudinal studies should further explore the development of
      emotion regulation and social functioning in cochlear implant children.

PMID- 22459036
TI  - Effects of brain death on organ quality and transplant outcome.
AB  - The inferiority of organs from brain dead donors is reflected by impaired graft
      survival and patient outcome. Brain death effects hemodynamic stability, hormonal
      changes, and neuroimmunologic effects and unleashes a cascade of inflammatory
      events. Despite considerable efforts in experimental and clinical research, most
      of the mechanisms linked to brain death are only appreciated on a descriptive
      level. This overview presents our current understanding of the pathophysiology
      and consequences of brain death on organ injury and summarizes available
      therapeutic interventions.

PMID- 22459038
TI  - The role of normothermic extracorporeal perfusion in minimizing ischemia
      reperfusion injury.
AB  - The primary objective of organ preservation is to deliver a viable graft with
      minimal risk of impaired postoperative graft function. In current clinical
      practice, preservation of transplanted organs is based on hypothermia. Organs are
      flushed and stored using specific preservation solutions to reduce cellular
      metabolism and prevent cell swelling. However, the ongoing organ donor shortage
      and consequent expansion of donor criteria to include the use of grafts that
      would once have been discarded as unsuitable have underlined the need for a
      technique that prevents any further damage during the preservation period. The
      principle of normothermic machine perfusion preservation is the maintenance of
      cellular metabolism in a physiological environment throughout the preservation
      period. Normothermic preservation, at least in theory, thereby overcomes the 3
      major weaknesses inherent in traditional static cold storage by (1) avoiding
      ischemia/reperfusion injury, (2) avoiding cold injury, and (3) allowing viability
      assessment. Furthermore, normothermic machine perfusion might transpire to be the
      ideal vehicle to deliver other therapeutic interventions during preservation to
      modulate and optimize the graft before transplantation. By restoring function in
      marginal donor organs and enabling the clinician to appraise its viability, the
      donor pool might be greatly expanded.

PMID- 22459039
TI  - Bone marrow mononuclear cells and mannose receptor expression in focal cortical
      ischemia.
AB  - The use of bone marrow mononuclear cells (BMMCs) has been shown as a putative
      efficient therapy for stroke. However, the mechanisms of therapeutic action are
      not yet completely known. Mannose receptor (MR) is a subgroup of the C-type
      lectin receptor superfamily involved in innate immune response in several
      tissues. Although known primarily for its immune function, MR also has important
      roles in cell migration, cell debris clearance and tissue remodeling during
      inflammation and wound healing. Here we analyzed MR expression in brains of rats
      one week after induction of unilateral focal cortical ischemia by
      thermocoagulation in blood vessels of sensorimotor cortex. Additionally, we
      evaluated possible changes in such expression in cortices of rats subjected to
      ischemia plus treatment with BMMCs. Our results showed high expression of MR in
      an unknown GFAP(+) cell type and in phagocytic macrophages/microglia within the
      lesion boundary zone whereas in the non-injured (contralateral) cortical
      parenchyma, low levels of MR expression were observed. Moreover, therapy with
      BMMCs induced overexpression of MR in ipsilateral (injured) cortex. Previous
      studies from our group have shown functional recovery and decreased
      neurodegeneration in BMMC-treated rats in the same model of focal cortical
      ischemia. Thus, we suggest that ischemic injury induces large increase in MR
      expression as part of a mechanism for clearance of damage-associated molecular
      patterns (DAMPs). In addition, induction of MR overexpression by BMMCs might
      increase the efficiency of clearance, being one of the protective mechanisms of
      these cells.

PMID- 22459040
TI  - Organization of hyperactive microglial cells in trigeminal spinal subnucleus
      caudalis and upper cervical spinal cord associated with orofacial neuropathic
      pain.
AB  - The aim of this study was to evaluate spatial organization of hyperactive
      microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical
      spinal cord (C1), and to clarify the involvement in mechanisms underlying
      orofacial secondary hyperalgesia following infraorbital nerve injury. We found
      that the head-withdrawal threshold to non-noxious mechanical stimulation of the
      maxillary whisker pad skin was significantly reduced in chronic constriction
      injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION
      CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial
      skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well
      as the 2nd branch area. Hyperactive microglial cells in Vc and C1 were observed
      on days 3 and 7 after ION-CCI. On day 3 after ION-CCI, a large number of
      phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR)
      cells were observed in Vc and C1. Many hyperactive microglial cells were also
      distributed over a wide area of Vc and C1 innervated by the trigeminal nerve. The
      intraperitoneal administration of minocycline significantly reduced the
      activation of microglial cells and the number of pERK-IR cells in Vc and C1, and
      also significantly attenuated the development of mechanical allodynia.
      Furthermore, enhanced background activity and mechanical evoked responses of Vc
      wide dynamic range neurons in ION-CCI rats were significantly reversed following
      minocycline administration. These findings suggest that activation of microglial
      cells over a wide area of Vc and C1 is involved in the enhancement of Vc and C1
      neuronal excitability in the early period after ION-CCI, resulting in the
      neuropathic pain in orofacial areas innervated by the injured as well as
      uninjured nerves.

PMID- 22459037
TI  - Current strategies to minimize hepatic ischemia-reperfusion injury by targeting
      reactive oxygen species.
AB  - Ischemia-reperfusion is a major component of injury in vascular occlusion both
      during liver surgery and during liver transplantation. The pathophysiology of
      hepatic ischemia-reperfusion includes a number of mechanisms including oxidant
      stress that contribute to various degrees to the overall organ damage. A large
      volume of recent research has focused on the use of antioxidants to ameliorate
      this injury, although results in experimental models have not translated well to
      the clinic. This review focuses on critical sources and mediators of oxidative
      stress during hepatic ischemia-reperfusion, the status of current antioxidant
      interventions, and emerging mechanisms of protection by preconditioning. While
      recent advances in regulation of antioxidant systems by Nrf2 provide interesting
      new potential therapeutic targets, an increased focus must be placed on more in
      depth mechanistic investigations in hepatic ischemia-reperfusion injury and
      translational research in order to refine current strategies in disease
      management.

PMID- 22459041
TI  - The perceptual and neuronal stability of the rubber hand illusion across contexts
      and over time.
AB  - The rubber hand illusion (RHI) offers the opportunity to systematically
      manipulate the experience of embodiment, which is here used to describe the
      subjective integration of an external object into one's body representation.
      Among the cortical regions involved in the processing of body perception, the
      ventral premotor cortex seems to be crucial in the integration of visuotactile
      stimuli. However, it is not known if the perceived vividness of the RHI is a
      trait or a state variable. In the present study, we varied the setup of the RHI
      to test the stability of perception. The illusion was induced in two different
      contexts, with either a horizontal or vertical displacement of the rubber hand in
      respect to the real hand. Further, the RHI was induced twice with an interval of
      at least six months and long-term changes on the perceptual and behavioral level
      were evaluated. Finally, we measured the long-term stability of cortical activity
      during the induction of a vertical RHI using functional magnetic resonance
      imaging. We found that a vertical setup induced higher ratings of illusory
      embodiment of the rubber hand than a horizontal setup, but the responses to both
      setups were significantly correlated. There was high intra-individual long-term
      stability of the subjective perception of illusory embodiment but a lower
      stability on the behavioral level. The functional magnetic resonance imaging data
      suggest temporally stable ventral premotor cortex processing. These results
      indicate that dynamic changes in perceived limb ownership by the induction of the
      RHI are trait-like.

PMID- 22459042
TI  - Understanding spatio-temporal strategies of adult zebrafish exploration in the
      open field test.
AB  - Zebrafish (Danio rerio) are emerging as a useful model organism for neuroscience
      research. Mounting evidence suggests that various traditional rodent paradigms
      may be adapted for testing zebrafish behavior. The open field test is a popular
      rodent test of novelty exploration, recently applied to zebrafish research. To
      better understand fish novelty behavior, we exposed adult zebrafish to two
      different open field arenas for 30 min, assessing the amount and temporal
      patterning of their exploration. While (similar to rodents) zebrafish scale their
      locomotory activity depending on the size of the tank, the temporal patterning of
      their activity was independent of arena size. These observations strikingly
      parallel similar rodent behaviors, suggesting that spatio-temporal strategies of
      animal exploration may be evolutionarily conserved across vertebrate species. In
      addition, we found interesting oscillations in zebrafish exploration, with the
      per-minute distribution of their horizontal activity demonstrating sinusoidal
      like patterns. While such patterning is not reported for rodents and other higher
      vertebrates, a nonlinear regression analysis confirmed the oscillation patterning
      of all assessed zebrafish behavioral endpoints in both open field arenas,
      revealing a potentially important aspect of novelty exploration in lower
      vertebrates.

PMID- 22459043
TI  - Distinct human face representations in the perirhinal cortex and fusiform gyrus.
AB  - Face representation, which is believed to be processed in the temporal visual
      pathway, has been extensively investigated in humans and monkeys through
      neuroimaging and electroneurophysiology. Lesion studies in monkeys indicate that
      simple facial features are processed in the caudal regions, and that the combined
      and integrated features of the face are stored in the perirhinal cortex (PRC).
      However, this hypothesis still lacks experimental evidence in normal human
      subjects; therefore, we conducted 2 functional magnetic resonance imaging
      experiments to investigate whether the function of the PRC differs from that of
      conventional face-related areas during face recognition tests. In experiment 1,
      normal subjects learned 6 facial identity-figure associations before scanning,
      and their brain activity was measured during recognition testing of correct and
      incorrect face-figure pairs in 3 different angles. The degree of activation in
      the PRC differed among the facial angles, and activation in response to frontal
      views was greater than that to other views. In experiment 2, where face angle,
      but not identity, was paired with an abstract figure, activation was
      significantly greater in response to the frontal view than that to other views.
      In contrast, the degree of activation in conventional face-related areas, i.e.,
      the fusiform gyrus, did not differ among viewing angles in both experiments. The
      results indicate that the function of face representation in the PRC differs from
      that in the conventional face-related areas, and that a frontal view of the face
      plays a role in the activation of face representation stored in the PRC.

PMID- 22459044
TI  - RGS2 mediates the anxiolytic effect of oxytocin.
AB  - The neuropeptide oxytocin (OT) has been shown to exert multiple functions in both
      males and females, and to play a key role in the regulation of emotionality in
      the central nervous system (CNS). OT has an anxiolytic effect in the CNS of
      rodents and humans. However, the molecular mechanisms of this effect are unclear.
      Here we show that OT induced the expression of regulator of G-protein signaling 2
      (RGS2), a regulatory factor for anxiety, in the central amygdala (CeA) of female
      mice. Bath application of OT increased RGS2 levels in slices of the amygdala of
      virgin mice. RGS2 levels in the CeA were higher in lactating mice than in virgin
      mice. In contrast, RGS2 levels in mice that had given birth did not increase when
      the pups were removed. Acute restraint stress for 4h induced RGS2 expression
      within the CeA, and local administration of an OT receptor antagonist inhibited
      this expression. Behavioral experiments revealed that transient restraint stress
      had an anxiolytic effect in wild-type females, and RGS2 levels in the CeA
      correlated with the anxiolytic behavior. By contrast, in the OT receptor
      deficient mice, restraint stress neither increased RGS2 levels in the CeA nor had
      an anxiolytic effect. These results suggest that OT displays an anxiolytic effect
      through the induction of RGS2 expression in the CNS.

PMID- 22459045
TI  - Altered pupillary light reflex in PACAP receptor 1-deficient mice.
AB  - The pupillary light reflex (PLR) is regulated by the classical photoreceptors,
      rods and cones, and by intrinsically photosensitive retinal ganglion cells
      (ipRGCs) expressing the photopigment melanopsin. IpRGCs receive input from rods
      and cones and project to the olivary pretectal nucleus (OPN), which is the
      primary visual center involved in PLR. Mice lacking either the classical
      photoreceptors or melanopsin exhibit some changes in PLR, whereas the reflex is
      completely lost in mice deficient of all three photoreceptors. The neuropeptide
      pituitary adenylate cyclase-activating polypeptide (PACAP) is co-stored with
      melanopsin in ipRGCs and mediates light signaling to the brain via the specific
      PACAP receptor 1 (PAC1R). Here, we examined the occurrence of PACAP and PAC1R in
      the mouse OPN, and studied if lack of PAC1R affected the PLR. PACAP
      immunoreactive nerve fibers were shown in the mouse OPN, and by in situ
      hybridization histochemistry, we demonstrated the presence of PAC1R mRNA. Mice
      lacking PAC1R exhibited a significantly attenuated PLR compared to wild type mice
      upon light stimulation, and the difference became more pronounced as light
      intensity was increased. Our findings accord well with observations of the PLR in
      the melanopsin-deficient mouse. We conclude that PACAP/PAC1R signaling is
      involved in the sustained phase of the PLR at high irradiances.

PMID- 22459046
TI  - An in vitro ischemic penumbral mimic perfusate increases NADPH oxidase-mediated
      superoxide production in cultured hippocampal neurons.
AB  - The currently accepted scheme for reactive oxygen species production during
      ischemia/reperfusion injury is characterized by a deleterious mitochondria
      derived burst of radical generation during reperfusion; however, recent
      examination of the penumbra suggests a central role for NADPH-oxidase (Nox)
      mediated radical generation during the ischemic period. Therefore, we utilized a
      novel in vitro model of the penumbra to examine the free radical profile of
      ischemic murine hippocampal neurons using electron paramagnetic resonance
      spectroscopy, and also the role of Nox in this generation and in cell fate. We
      report that free radical production increased ~75% at 2 h of ischemia, and this
      increase was abolished by: (1) scavenging of extracellular free radicals with
      superoxide dismutase (SOD), (2) a general anion channel antagonist, or (3) the
      Nox inhibitor apocynin. Similarly, at 24 h of ischemia, [ATP] decreased >95% and
      vital dye uptake increased 6-fold relative to controls; whereas apocynin, the Cl(
      ) channel antagonist 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), or the free
      radical scavenger N-acetyl cysteine (NAC) each provided moderate neuroprotection,
      ameliorating 13-32% of [ATP]-depletion and 19-56% of vital dye uptake at 24 h.
      Our results support a cytotoxic role for Nox-mediated free radical production
      from penumbral neurons during the ischemic period.

PMID- 22459047
TI  - RNA-mediated neurodegeneration in fragile X-associated tremor/ataxia syndrome.
AB  - Carriers of fragile X syndrome (FXS) have FMR1 alleles, called premutations, with
      a number of 5'-untranslated-CGG repeats somewhere between patients, who have over
      200 repeats, and normal individuals, with fewer than 60 repeats. Fragile X
      associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative
      disorder, has been recognized in older male fragile X premutation carriers, and
      FXTAS is uncoupled from the neurodevelopmental disorder, FXS. Several lines of
      evidence have led to the proposal of an RNA (fragile X premutation rCGG repeat)
      mediated gain-of-function toxicity model for FXTAS, in which rCGG repeat-binding
      proteins (RBPs) could become functionally limited by their sequestration to
      lengthy rCGG repeats. In this review, we will discuss the recent progress towards
      understanding the molecular basis of RNA-mediated neurodegeneration in FXTAS.
      This article is part of a Special Issue entitled: RNA-Binding Proteins.

PMID- 22459048
TI  - Efficacy of tailored computer-based neurorehabilitation for improvement of
      movement initiation in Parkinson's disease.
AB  - While Parkinson's disease (PD) is considered a motor disorder, motor signs of PD
      can be exacerbated by cognitive dysfunction. We evaluated the efficacy of a
      computer-based cognitive rehabilitation training program designed to improve
      motor-related executive function. Thirty people with PD and 21 controls
      participated in the 10-day training. Training consisted of a two-phase button
      press task. First, subjects produced an externally cued (EC) digit sequence,
      typing numbers displayed on the computer screen. Second, subjects were prompted
      to generate the same sequence in the absence of the number display (internally
      represented sequence, IR). Sequence length was automatically adjusted to maintain
      87% correct performance. Participants were evaluated before and after training
      using a fixed version of the training task, and generalization of training was
      assessed using measures involving IR motor sequencing, switching and activities
      of daily living. PD participants were divided into two groups, those who showed
      impairment in IR motor sequence production prior to training (N=14) and those
      whose performance was similar to controls (N=16). Following training the impaired
      PD group showed significantly greater reduction in sequence initiation and
      completion time and in error rate for IR conditions compared to the unimpaired PD
      and control groups. All groups improved on Trails B-A, and pre-training Trails B
      was identified as a predictor of training-based improvement in IR sequence
      completion time and error rate. Our findings highlight the importance of
      neurorehabilitation tailored to the specific cognitive deficits of the PD
      patient.

PMID- 22459049
TI  - Increased phosphorylation of dynamin-related protein 1 and mitochondrial fission
      in okadaic acid-treated neurons.
AB  - Mitochondrial dysfunction is a prominent feature of neurodegenerative diseases
      and aging. A recent study showed that phosphorylation of dynamin-related protein
      1 (Drp1) is increased in Alzheimer's disease (AD) brains compared to control
      brains, indicating that mitochondrial fission is increased in AD brains. Here, we
      showed that Drp1 phosphorylation and mitochondrial fission were also increased in
      rat cortical neurons treated with okadaic acid (OA), which inhibits protein
      phosphatase-2A (PP2A) and induces AD-like tau phosphorylation and neuronal death.
      Concurrent with this abnormal increase in mitochondrial fission, mitochondrial
      reactive oxygen species (ROS) were also increased, suggesting mitochondrial
      damage and detrimental effects on cell survival. Parkin, which is necessary for
      mitophagy of abnormal mitochondria and has been shown to be decreased in AD
      brains, and K48-linked polyubiquitin were also decreased in OA-treated neurons,
      suggesting that the mitophagic process required to degrade detrimental ROS
      generating mitochondria is disabled. Collectively, our results demonstrate that
      abnormal mitochondrial fission, ROS generation, and inefficient mitophagy all
      occur in PP2A-inhibited neurons, as in AD brains, and suggest that this model
      could be used in developing inhibitors of mitochondrial fission or ROS
      generation.

PMID- 22459050
TI  - Increased expression of matrix metalloproteinase 9 in cortical lesions from
      patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.
AB  - The malformative cortical lesions in the cerebral cortex that are characteristic
      of focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex
      (TSC) are well-recognized causes of chronic intractable epilepsy in children.
      Increasing evidence suggests that extracellular matrix molecules play important
      roles in epileptogenesis. Matrix metalloproteinase 9 (MMP9), a typical
      extracellular matrix proteolytic protease, has been shown to participate in the
      occurrence of seizures in experimental models. In the present study, we used
      immunoblotting to analyze the levels of MMP9 protein in FCDIIb lesions, TSC
      tubers and control samples, which included epileptic neocortices from temporal
      lobe epilepsy and non-epileptic normal cortices (CTX). The cellular distribution
      of MMP9 was further investigated by immunohistochemical methods. Our findings
      demonstrated the elevated levels of the inactive and active forms of MMP9 protein
      in FCDIIb and TSC lesions compared with CTX. Furthermore, the immunohistochemical
      results showed that MMP9 was characteristically expressed in the following
      misshapen cells: hypertrophic neurons, dysmorphic neurons, balloon cells and
      giant cells. Additionally, double immunofluorescent staining revealed that the
      reactive astrocytes, but not the microglia, expressed high levels of MMP9. Taken
      together, our findings suggest that the overexpression and spatial distribution
      patterns of MMP9 may be linked with the intractable epilepsy caused by FCDIIb and
      TSC.

PMID- 22459051
TI  - Netrin-1 improves spatial memory and synaptic plasticity impairment following
      global ischemia in the rat.
AB  - Cerebral ischemia, which is the second and most common cause of mortality,
      affects millions of individuals worldwide. The present study was performed to
      investigate whether intrahippocampal administration of netrin-1 could improve
      spatial memory impairment in radial arm maze task and restore long-term
      potentiation (LTP) in 4-vessel occlusion model of global ischemia. The results
      showed that intrahippocampal infusion of nerin-1 24 h after ischemia (at both
      doses of 400 and 800 ng) significantly ameliorated spatial memory impairment and
      at a dose of 800 ng was capable to improve synaptic dysfunction as observed by
      recovery of population spike component of basal evoked potential and LTP through
      enhancement of excitability and normalization of paired pulse response. Taken
      together, the present study shows that netrin-1 dose-dependently ameliorates
      spatial memory impairment and improves synaptic dysfunction as observed by
      recovery of population spike component of basal evoked potential and LTP in rats
      with global ischemia.

PMID- 22459052
TI  - What characterises the privately insured in universal health care systems? A
      review of the empirical evidence.
AB  - OBJECTIVES: This paper reviews the empirical literature on what characterises
      individuals with voluntary private health insurance (VPHI) in universal health
      care systems and assesses how well the empirical evidence corresponds with the
      theoretical predictions. METHODS: Empirical studies were identified by performing
      searches in electronic databases. RESULTS: The literature search identified a
      total of 24 articles and 15 working papers, the majority of which were published
      within the recent decade. Socioeconomic characteristics are generally found to be
      important determinants of VPHI coverage. In accordance with economic theory, the
      probability of taking out VPHI on an individual basis is consistently found to
      increase with income. Likewise, the empirical evidence generally supports the
      theoretical prediction of individuals selecting themselves into duplicate VPHI
      based on the quality of care available within the universal health care system,
      just as the demand for VPHI is consistently found to be negatively affected by
      the insurance premium. On the contrary, the empirical evidence on the importance
      of risk preferences is sparse and points in different directions. Finally, with a
      few exceptions, the privately insured are found to be in equal or better health
      compared to the remaining population. In most settings, the positive association
      between health and VPHI coverage may be attributed to risk rating of insurance
      premiums and eligibility requirements, while it may be interpreted as evidence of
      advantageous selection in their absence.

PMID- 22459053
TI  - Primary central nervous system lymphoma.
AB  - Primary central nervous system lymphoma is an aggressive lymphoma with a
      molecular biology and genetic profile that appears to be distinct from other
      types of diffuse large B-cell lymphoma. The median survival after whole brain
      radiotherapy alone is poor, but is significantly improved after high-dose
      methotrexate-based combination chemotherapy. The rarity of primary central
      nervous system lymphoma means that randomised studies have proved challenging,
      particularly as many patients are elderly and more susceptible to the toxic
      effects associated with these treatments. Promising treatment strategies are
      emerging and, wherever possible, patients should be treated within clinical
      trials. Quality of life and neurocognitive data should be collected prospectively
      to assess the effect of the disease and treatment.

PMID- 22459054
TI  - Perceiving an exclusive cause of affect prevents misattribution.
AB  - Affect misattribution occurs when affective cues color subsequent unrelated
      evaluations. Research suggests that affect misattribution decreases when one is
      aware that affective cues are unrelated to the evaluation at hand. We propose
      that affect misattribution may even occur when one is aware that affective cues
      are irrelevant, as long as the source of these cues seems ambiguous. When source
      ambiguity exists, affective cues may freely influence upcoming unrelated
      evaluations. We examined this using an adapted affect misattribution procedure
      where pleasant and unpleasant responses served as affective cues that could
      influence later evaluations of unrelated targets. These affective cues were
      either perceived as reflecting a single source (i.e., a subliminal affective
      picture in Experiment 1; one's internal affective state in Experiment 2), or as
      reflecting two sources (i.e., both) suggesting source ambiguity. Results show
      that misattribution of affect decreased when participants perceived affective
      cues as representing one source rather than two.

PMID- 22459056
TI  - The influence of bone cement type on production of fretting wear on the femoral
      stem surface: a preliminary study.
AB  - BACKGROUND: It has been reported that bone cement correlates with survivorship of
      cemented total hip replacement. However, little research has been published to
      investigate the influence of bone cement type on production of fretting wear on
      the femoral stem. METHODS: In the present study, we performed six in vitro wear
      simulations using the same type of femoral stem (polished Exeter V40TM) and three
      different bone cements (Simplex P, Palacos R, and CMW 3). FINDINGS: Fretting wear
      was consistently reproduced on the stem surface and the wear locations compared
      well with the results of retrieval studies. Selected 3D surface parameters were
      utilised to quantitatively evaluate fretting wear and no significant difference
      was identified in terms of fretting wear severity between these simulations. The
      bone cements were all badly damaged in those sites contacting the fretting wear
      areas on the femoral stem. Additionally, there were plenty of wear debris present
      on the cement surface, and the energy dispersive X-ray analysis confirmed that it
      was just cement particles for Simplex P bone cement, whilst it included metallic
      particles for Palacos R and CMW 3 bone cements. INTERPRETATION: This preliminary
      study shed some light on the influence of bone cement type on production of
      fretting wear on the femoral stem surface but further research is needed to gain
      a better understanding on this issue.

PMID- 22459055
TI  - Focal brain cooling terminates the faster frequency components of epileptic
      discharges induced by penicillin G in anesthetized rats.
AB  - OBJECTIVE: The goal of the study was to investigate the effects of focal brain
      cooling on epileptic discharges (EDs) and background rhythms in the sensorimotor
      cortex of anesthetized rats using spectral analysis of electroencephalography
      (EEG). METHODS: Penicillin G was administered intracortically into superficial
      layers of the left sensorimotor cortex and EDs were induced. Focal brain cooling
      was achieved using a cooling device attached to the cortical surface. The
      cortical surface was cooled to 25 degrees C, 20 degrees C and 15 degrees C, and
      EEG was continuously recorded just beneath the cooling device. EEG spectral
      powers were determined using fast Fourier transform before and during cooling.
      RESULTS: Penicillin G induced EDs and increased the Alpha and Beta power spectra.
      Cooling suppressed EDs with an effect that depended on the brain temperature.
      Cooling to 25 degrees C attenuated Beta powers, cooling to 20 degrees C
      attenuated Alpha and Beta powers, and cooling to 15 degrees C suppressed spectral
      powers ranging from Delta to Beta bands. CONCLUSIONS: These results suggest that
      focal brain cooling can terminate EDs in the cortex and suppress spectral powers
      with a temperature-dependent effect. SIGNIFICANCE: These findings may contribute
      to development of a new clinical treatment for patients with epilepsy.

PMID- 22459057
TI  - Maximizing the role of emergency departments in the prevention of violence:
      developing an approach in South London.
AB  - This article presents an overview of a partnership between public health teams in
      two primary care trusts in South East London, their local acute hospital trusts,
      and crime and disorder reduction partnerships to support the reduction of harm
      from violence. It discusses recent developments in violence prevention in
      emergency departments in the UK, and developments around outreach and case
      management, more common in the USA. It then outlines the elements of the violence
      prevention project being conducted in South East London.

PMID- 22459058
TI  - Determining E. coli burden on pasture in a headwater catchment: combined field
      and modelling approach.
AB  - Empirical monitoring studies of catchment-scale Escherichia coli burden to land
      from agriculture are scarce. This is not surprising given the complexity
      associated with the temporal and spatial heterogeneity in the excretion of
      livestock faecal deposits and variability in microbial content of faeces.
      However, such information is needed to appreciate better how land management and
      landscape features impact on water quality draining agricultural landscapes. The
      aim of this study was to develop and test a field-based protocol for determining
      the burden of E. coli in a small headwater catchment in the UK. Predictions of E.
      coli burden using an empirical model based on previous best estimates of
      excretion and shedding rates were also evaluated against observed data. The
      results indicated that an empirical model utilising key parameters was able to
      satisfactorily predict E. coli burden on pasture most of the time, with 89% of
      observed values falling within the minimum and maximum range of predicted values.
      In particular, the overall temporal pattern of E. coli burden on pasture is
      captured by the model. The observed and predicted values recorded a disagreement
      of >1 order of magnitude on only one of the nine sampling dates throughout an
      annual period. While a first approximation of E. coli burden to land, this field
      based protocol represents one of the first comprehensive approaches for providing
      a real estimate of a dynamic microbial reservoir at the headwater catchment scale
      and highlights the utility of a simple dynamic empirical model for a more
      economical prediction of catchment-scale E. coli burden.

PMID- 22459059
TI  - Predictors of PCP, OH-PCBs, PCBs and chlorinated pesticides in a general female
      Norwegian population.
AB  - The aims of the current study were to assess plasma concentrations and predictors
      of halogenated phenolic compounds (HPCs), polychlorinated biphenyls (PCBs) and
      chlorinated pesticides in a representative group of postmenopausal Norwegian
      women (n=311, mean age: 56 years). In addition to delivering a blood sample, the
      participants had also filled out a detailed questionnaire regarding their current
      health status, use of medication and dietary habits, etc. The association between
      a large number of dietary variables, lifestyle factors and plasma concentration
      of organic pollutants were investigated using multivariate statistics. Within the
      current study group, p,p'-DDE (median: 903 ng/L w.w.) and pentachlorophenol (PCP,
      median: 711 ng/L w.w.) were the dominating compounds on a wet weight basis and
      were present in considerable higher concentrations than the PCBs, the
      hydroxylated PCBs (OH-PCBs) and the remaining chlorinated pesticides. Of the
      PCBs, PCB 153 was detected in highest concentrations, whereas 4-OH-PCB187 was
      present in highest concentration of the selected OH-PCBs. The ratio of SigmaOH
      PCB to SigmaPCB varied between 0.06 and 0.77 ng/L and were significantly lower in
      individuals with higher SigmaPCB concentration. PCP did not co-vary with the
      other contaminants, indicating a different route of exposure. No clear food
      cluster was positively associated with PCP exposure; however intake of marine
      food was negatively linked to PCP concentration and age and being a non-smoker
      were positive predictors of PCP. The other investigated contaminants co-varied
      and were positively associated with age, plasma concentrations of marine derived
      omega-3 fatty acids and a traditional Norwegian fish and bread based diet. The
      difference in contaminant concentration between high, medium and low consumers of
      total marine food were however marginal for the dominating PCBs and chlorinated
      pesticides. The current results indicate however that marine food in itself could
      be a source of some of the OH-PCBs, regardless of their PCB precursors. As PCP is
      one of the dominating organic contaminants within the general female Norwegian
      population, future research on human concentrations, exposure routes and
      potential health effects of PCP is encouraged. Continued monitoring of human OH
      PCB levels should also be performed as they could be present at levels almost as
      high as the PCBs and they are expected to be more toxic than their mother
      substances.

PMID- 22459060
TI  - Balancing ethics and science in pediatric pain intervention trials.

PMID- 22459062
TI  - Origin and correction of magnetic field inhomogeneity at the interface in
      biphasic NMR samples.
AB  - The use of susceptibility matching to minimize spectral distortion of biphasic
      samples layered in a standard 5 mm NMR tube is described. The approach uses magic
      angle spinning (MAS) to first extract chemical shift differences by suppressing
      bulk magnetization. Then, using biphasic coaxial samples, magnetic
      susceptibilities are matched by titration with a paramagnetic salt. The matched
      phases are then layered in a standard NMR tube where they can be shimmed and
      examined. Linewidths of two distinct spectral lines, selected to characterize
      homogeneity in each phase, are simultaneously optimized. Two-dimensional
      distortion-free, slice-resolved spectra of an octanol/water system illustrate the
      method. These data are obtained using a 2D stepped-gradient pulse sequence
      devised for this application. Advantages of this sequence over slice-selective
      methods are that acquisition efficiency is increased and processing requires only
      conventional software.

PMID- 22459063
TI  - Employment, family leave, and parents of newborns or seriously ill children.
AB  - OBJECTIVES: Parents of newborns and children with special health care needs
      (CSHCN) often experience conflict between employment and family responsibilities.
      Family leave benefits such as the federal Family and Medical Leave Act and
      California's Paid Family Leave Insurance program help employed parents miss work
      to bond with a newborn or care for an ill child. The use of these benefits,
      however, is rare among mothers of CSHCN and fathers in general and limited even
      among mothers of newborns. We explored barriers to and experiences with leave
      taking among parents of newborns and CSHCN. METHODS: We conducted semistructured
      qualitative interviews in 2008 with 10 mothers and 10 fathers of newborns and 10
      mothers and 10 fathers of CSHCN in Los Angeles to explore their need for and
      experiences with family leave. Qualitative analytical techniques were used to
      identify themes in the transcripts. RESULTS: All parents reported difficulties in
      accessing and using benefits, including lack of knowledge by employers,
      complexity of rules and processes, and inadequacy of the benefits themselves.
      Parents of CSHCN also described being too overwhelmed to rapidly seek and process
      information in the setting of urgent and often unexpected health crises. Most
      parents expressed a clear desire for expert guidance and saw hospitals and
      clinics as potentially important providers. CONCLUSIONS: Even when parents are
      aware of family leave options, substantial barriers prevent many, especially
      parents of CSHCN, from learning about or applying for benefits. Clinics and
      hospitals might be opportune settings to reach vulnerable parents at times of
      need.

PMID- 22459064
TI  - Development of an algorithm for the diagnosis of otitis media.
AB  - BACKGROUND: The relative importance of signs and symptoms in the diagnosis of
      otitis media has not been adequately evaluated. This has led to a large degree of
      variation in the criteria used to diagnose otitis media, which has resulted in
      inconsistencies in clinical care and discrepant research findings. METHODS: A
      group of experienced otoscopists examined children presenting for primary care.
      We investigated the signs and symptoms that these otoscopists used to distinguish
      acute otitis media (AOM), otitis media with effusion (OME), and no effusion. We
      used recursive partitioning to develop a diagnostic algorithm. To assess the
      algorithm, we validated it in an independent dataset. RESULTS: Bulging of the
      tympanic membrane (TM) was the main finding that otoscopists used to discriminate
      AOM from OME; information regarding the presence or absence of other signs and
      symptoms added little to the diagnostic process. Overall, 92% of children with
      AOM had a bulging TM compared with 0% of children with OME. Opacification and/or
      an air-fluid level was the main finding that the otoscopists used to discriminate
      OME from no effusion; 97% of children diagnosed with OME had an opaque TM
      compared with 5% of children diagnosed with no effusion. An algorithm that used
      bulging and opacification of the TM correctly classified 99% of ears in an
      independent dataset. CONCLUSIONS: Bulging of the TM was the finding that best
      discriminated AOM from OME. The algorithm developed here may prove to be useful
      in clinical care, research, and education concerning otitis media.

PMID- 22459066
TI  - Analysis of barriers and success factors affecting the adoption of sustainable
      management of municipal solid waste in Nigeria.
AB  - The poor state of solid waste management in cities of developing countries is
      fast assuming the scale of a major social/environmental challenge. The main
      drivers of the waste problem in Nigeria, for instance, are poverty, high
      population and urbanization growth rates, compounded by a weak and underfunded
      infrastructure. The gravity of this problem is perhaps best reflected in the
      level of attention given to it in the United Nations Millennium Declaration in
      September, 2000. Three of the eight Millennium Development Goals (MDGs) in the
      Declaration have waste or resource efficiency implications. In response to the
      waste challenge many developed countries have embarked upon ambitious
      environmental reforms, recording remarkable advances in best practises and
      sustainable management of their Municipal Solid Waste (MSW). The same cannot be
      said for most countries in Sub-Sahara Africa, however, as a result of several
      barriers militating against sustainable MSW management. Adopting a questionnaire
      interview methodology, this study surveyed 1557 respondents' drawn from
      households, business and waste policy-makers in Abuja, Nigeria. Data analysis was
      carried out using the Statistical Programme for Social Sciences, (SPSS).
      Multivariate statistical analysis was used to carry out a between subjects
      multiple comparison of respondents views on the barriers as well as success
      factors affecting MSW management in the case study area. Findings point towards
      the need for a sustained public education programme on waste prevention and reuse
      as the panacea to waste problems in Nigeria. Based on the findings, a case is
      made for the adaptation of globally successful waste management best practises
      and strategies to suit local conditions.

PMID- 22459065
TI  - Brachytherapy for prostate cancer does not influence long-term depression rate.
AB  - PURPOSE: Current literature describes concern for an increase in depression owing
      to treatment of prostate cancer. Here, depression and coping up to 8 years
      posttreatment are described for patients treated with (125)I brachytherapy for
      localized prostate cancer. METHODS AND MATERIALS: Between December 2000 and June
      2010, 132 patients received questionnaires at: baseline, 1 month, 6 months, 1
      year, and 8 years posttreatment. The measures included the Center for
      Epidemiologic Studies Depression Scale (CES-D) and the Utrecht Coping List. Also
      general quality of life measures were used: the Short Form Health Survey (RAND
      36), the European Organization for Research and Treatment of Cancer C30
      questionnaire (EORTC QLQ-C30+3) and a prostate cancer specific questionnaire
      (EORTC-PR25). Descriptive statistics were performed and correlations among
      depression, coping, and general quality of life measures were investigated.
      RESULTS: At baseline and all follow-up moments, approximately 10% of the patients
      had a CES-D score of 16 or more, indicating a clinically significant level of
      depressive symptoms. Depression did not seem to change in time. Active coping was
      the most predominant style of coping in problem situations. Coping strategy did
      not change in time. No relevant correlations were found between coping and
      depression. No significant associations were found between CES-D mean score and
      patient characteristics (medical and demographic). Relevant negative correlations
      were found between depression and HRQOL variables vitality, emotional
      functioning, and mental health (rho>0.5). CONCLUSION: Prostate brachytherapy does
      not contribute to an increased risk of depression.

PMID- 22459067
TI  - Implications of volatile fatty acid profile on the metabolic pathway during
      continuous sulfate reduction.
AB  - Volatile fatty acid (VFA) profile is an important parameter in anaerobic reactors
      because it enables the assessment of metabolic pathways. Volatile fatty acids
      were monitored during sulfate reduction in a UASB (upflow anaerobic sludge
      blanket) reactor treating 2g/L sulfate concentration and with the organic loading
      increasing from 3.5 kg COD/m(3)d to 5.9 kg COD/m(3)d, for a 1-day residence time.
      In the absence of recirculation, the best outcome (65% reduction) was noticed
      with the lowest organic loading (3.55 kg/m(3)d). When recirculation was applied,
      sulfate reduction yields increased to 89%, corresponding to a sulfate removal
      rate of 1.94 kg SO(4)(2-)/m(3)d. The reactor performance was discussed in
      relation to microbial diversity and metabolic pathways. At high organic loading,
      two metabolic pathways account for lactate degradation: (i) lactate is oxidized
      to acetate and carbon dioxide by the incomplete-oxidizer SRB (sulfate-reducing
      bacteria) Desulfomonas, Desulfovibrio, Desulfolobus, Desulfobulbus and
      Desulfotomaculum spp.; (ii) lactate is converted to acetate by fermenting
      bacteria such as Clostridium sp. High propionate concentrations imply that there
      are low sulfate reduction efficiencies.

PMID- 22459068
TI  - Evaluation of targeting methods for implementation of best management practices
      in the Saginaw River Watershed.
AB  - Increasing concerns regarding water quality in the Great Lakes region are mainly
      due to changes in urban and agricultural landscapes. Both point and non-point
      sources contribute pollution to Great Lakes surface waters. Best management
      practices (BMPs) are a common tool used to reduce both point and non-point source
      pollution and improve water quality. Meanwhile, identification of critical source
      areas of pollution and placement of BMPs plays an important role in pollution
      reduction. The goal of this study is to evaluate the performance of different
      targeting methods in 1) identifying priority areas (high, medium, and low) based
      on various factors such as pollutant concentration, load, and yield, 2) comparing
      pollutant (sediment, total nitrogen-TN, and total phosphorus-TP) reduction in
      priority areas defined by all targeting methods, 3) determine the BMP relative
      sensitivity index among all targeting methods. Ten BMPs were implemented in the
      Saginaw River Watershed using the Soil and Water Assessment Tool (SWAT) model
      following identification of priority areas. Each targeting method selected
      distinct high priority areas based on the methodology of implementation. The
      concentration based targeting method was most effective at reduction of TN and
      TP, likely because it selected the greatest area of high priority for BMP
      implementation. The subbasin load targeting method was most effective at reducing
      sediment because it tended to select large, highly agricultural subbasins for BMP
      implementation. When implementing BMPs, native grass and terraces were generally
      the most effective, while conservation tillage and residue management had limited
      effectiveness. The BMP relative sensitivity index revealed that most combinations
      of targeting methods and priority areas resulted in a proportional decrease in
      pollutant load from the subbasin level and watershed outlet. However, the
      concentration and yield methods were more effective at subbasin reduction, while
      the stream load method was more effective at reducing pollutants at the watershed
      outlet. The results of this study indicate that emphasis should be placed on
      selection of the proper targeting method and BMP to meet the needs and goals of a
      BMP implementation project because different targeting methods produce varying
      results.

PMID- 22459069
TI  - Empirical analysis of factors explaining local governing bodies' trust for
      administering agencies in community-based conservation.
AB  - Nepal's conservation areas and community forests are generally considered as
      successful community-based conservation models. The paper's goal is to
      investigate the factors that consistently predict the level of trust local
      governing bodies have on administering agencies in these models. Both
      quantitative and qualitative data were collected through field research in the
      Annapurna Conservation Area (ACA) in the summer of 2007 and adjacent community
      forests in the fall of 2008. The Conservation Area Management Committee (CAMC)
      and the Community Forest User Committee (CFUC) are the functional decision-making
      entities at the local level in ACA and the community forests, respectively. I
      conducted one-on-one semi-structured interviews with 66 executive members of 10
      CAMCs and 67 members of 9 CFUCs. In multiple regression models relating the
      levels of trust committee members had for administering staff and agencies to a
      set of 7 theoretically informed covariates, 4 were statistically significant in
      ACA and 3 in the community forests. In ACA, committee members' overall assessment
      of the agency's performance, perceptions regarding the agency staff's
      understanding of local culture, perceptions regarding the equitable distribution
      of conservation benefits, and perceptions regarding the dependence upon the
      agency were statistically significant variables that influenced trust. In the
      community forests, committee members' overall assessment of the agency's
      performance, perceptions regarding the agency staff's understanding of local
      culture, and rational assessments of the benefits and costs associated with being
      a member explained significant variations in the levels of trust. The most
      consistent predictors of agency trust in both the models were committee members'
      overall assessment of the agency's performance, and perceptions regarding the
      agency staff's understanding of local culture. These findings suggest that
      natural resource management agencies can devise strategies for building trust
      with local governing bodies by a combination of above average performance and
      deeper understanding of local culture.

PMID- 22459070
TI  - The prioritisation of invasive alien plant control projects using a multi
      criteria decision model informed by stakeholder input and spatial data.
AB  - Invasions by alien plants are a significant threat to the biodiversity and
      functioning of ecosystems and the services they provide. The South African
      Working for Water program was established to address this problem. It needs to
      formulate objective and transparent priorities for clearing in the face of
      multiple and sometimes conflicting demands. This study used the analytic
      hierarchy process (a multi-criteria decision support technique) to develop and
      rank criteria for prioritising alien plant control operations in the Western
      Cape, South Africa. Stakeholder workshops were held to identify a goal and
      criteria and to conduct pair-wise comparisons to weight the criteria with respect
      to invasive alien plant control. The combination of stakeholder input (to develop
      decision models) with data-driven model solutions enabled us to include many
      alternatives (water catchments), that would otherwise not have been feasible. The
      most important criteria included the capacity to maintain gains made through
      control operations, the potential to enhance water resources and conserve
      biodiversity, and threats from priority invasive alien plant species. We selected
      spatial datasets and used them to generate weights that could be used to
      objectively compare alternatives with respect to agreed criteria. The analysis
      showed that there are many high priority catchments which are not receiving any
      funding and low priority catchments which are receiving substantial allocations.
      Clearly, there is a need for realigning priorities, including directing
      sufficient funds to the highest priority catchments to provide effective control.
      This approach provided a tractable, consensus-based solution that can be used to
      direct clearing operations.

PMID- 22459071
TI  - Promotion of growth and Cu accumulation of bio-energy crop (Zea mays) by
      bacteria: implications for energy plant biomass production and phytoremediation.
AB  - Three metal-resistant and plant growth-promoting bacteria (Burkholderia sp. GL12,
      Bacillus megaterium JL35 and Sphingomonas sp. YM22) were evaluated for their
      potential to solubilize Cu(2) (OH)(2)CO(3) in solution culture and their plant
      growth promotion and Cu uptake in maize (Zea mays, an energy crop) grown in a
      natural highly Cu-contaminated soil. The impacts of the bacteria on the Cu
      availability and the bacterial community in rhizosphere soils of maize were also
      investigated. Inductively coupled-plasma optical emission spectrometer analysis
      showed variable amounts of water-soluble Cu (ranging from 20.5 to 227 mgL(-1))
      released by the bacteria from Cu(2) (OH)(2)CO(3) in solution culture. Inoculation
      with the bacteria was found to significantly increase root (ranging from 48% to
      83%) and above-ground tissue (ranging from 33% to 56%) dry weights of maize
      compared to the uninoculated controls. Increases in Cu contents of roots and
      above-ground tissues varied from 69% to 107% and from 16% to 86% in the bacterial
      inoculated plants compared to the uninoculated controls, respectively.
      Inoculation with the bacteria was also found to significantly increase the water
      extractive Cu concentrations (ranging from 63 to 94%) in the rhizosphere soils of
      the maize plants compared to the uninoculated controls in pot experiments.
      Denaturing gradient gel electrophoresis and sequence analyses showed that the
      bacteria could colonize the rhizosphere soils and significantly change the
      bacterial community compositions in the rhizosphere soils. These results suggest
      that the metal-resistant and plant growth-promoting bacteria may be exploited for
      promoting the maize (energy crop) biomass production and Cu phytoremediation in a
      natural highly Cu-contaminated soil.

PMID- 22459072
TI  - Temporal stability of individual preferences for river restoration in Austria
      using a choice experiment.
AB  - Temporal stability of values (environmental preferences) is usually considered to
      be an indicator of the reliability of a valuation instrument because the values
      can be "reproduced" by follow-up experiments. The objective of this paper is to
      test temporal stability of individual preferences for river restoration by
      employing two identical choice experiments with a time difference of one year. We
      compared the results of two surveys carried out on the stretch of the Danube
      River between the Austrian capital of Vienna and the border to the Slovak
      Republic in 2007 and 2008. The choice experiment method considered economic costs
      and benefits of ecological improvements along the river, in order to value
      environmental resources. Using a multinomial logit and a mixed logit model for
      the two samples and a pooled sample, we found that preferences and willingness-to
      pay estimates for program attributes are not sensitive to time. The results
      suggest that, in the absence of an extreme event, individual preferences are
      robust over a short time period.

PMID- 22459074
TI  - Expanding roles of glutamate receptors in neurovascular regulation.

PMID- 22459073
TI  - Effect of sphingosine 1-phosphate (S1P) receptor agonists FTY720 and CYM5442 on
      atherosclerosis development in LDL receptor deficient (LDL-R-/-) mice.
AB  - OBJECTIVES: Sphingosine 1-phosphate (S1P)--a lysosphingolipid present in HDL-
      exerts atheroprotective effects in vitro, while FTY720, a non-selective S1P
      mimetic inhibits atherosclerosis in LDL receptor-deficient (LDL-R-/-) mice under
      conditions of severe hypercholesterolemia. We here examined the effect of FTY720
      and a selective S1P receptor type 1 agonist CYM5442 on atherosclerosis in
      moderately hypercholesterolemic LDL-R-/- mice. METHODS AND RESULTS: LDL-R-/- mice
      fed Western diet (0.25% cholesterol) were given FTY720 (0.4 mg/kg/day) or CYM5442
      (2.0 mg/kg/day) for 18 weeks. FTY720 but not CYM5422 persistently lowered blood
      lymphocytes, depleted CD4+ and CD8+ T cells in spleen and lymph nodes, and
      reduced splenocyte IL-2 secretion. However, both compounds reduced the activity
      of splenic and peritoneal macrophages as inferred from the down-regulated CD68
      and MHC-II expression in CD11b+ cells and the reduced IL-6 secretion in response
      to LPS, respectively. CYM5442 and FTY720 reduced weight gain, white adipose
      tissue depots and fasting glucose suggesting improvement of metabolic control,
      but failed to influence atherosclerosis in LDL-R-/- mice. CONCLUSION: Despite
      down-regulating macrophage function and--in case of FTY720--altering lymphocyte
      distribution CYM5442 and FTY720 fail to affect atherosclerosis in moderately
      hypercholesterolemic LDL-R-/- mice. We hypothesize that S1P mimetics exert
      atheroprotective effects only under conditions of increased cholesterol burden
      exacerbating vascular inflammation.

PMID- 22459075
TI  - Brain evolution and human neuropsychology: the inferential brain hypothesis.
AB  - Collaboration between human neuropsychology and comparative neuroscience has
      generated invaluable contributions to our understanding of human brain evolution
      and function. Further cross-talk between these disciplines has the potential to
      continue to revolutionize these fields. Modern neuroimaging methods could be
      applied in a comparative context, yielding exciting new data with the potential
      of providing insight into brain evolution. Conversely, incorporating an
      evolutionary base into the theoretical perspectives from which we approach human
      neuropsychology could lead to novel hypotheses and testable predictions. In the
      spirit of these objectives, we present here a new theoretical proposal, the
      Inferential Brain Hypothesis, whereby the human brain is thought to be
      characterized by a shift from perceptual processing to inferential computation,
      particularly within the social realm. This shift is believed to be a driving
      force for the evolution of the large human cortex. (JINS, 2012, 18, 394-401).

PMID- 22459076
TI  - Experiences in fragment-based drug discovery.
AB  - Fragment-based drug discovery (FBDD) has become established in both industry and
      academia as an alternative approach to high-throughput screening for the
      generation of chemical leads for drug targets. In FBDD, specialised detection
      methods are used to identify small chemical compounds (fragments) that bind to
      the drug target, and structural biology is usually employed to establish their
      binding mode and to facilitate their optimisation. In this article, we present
      three recent and successful case histories in FBDD. We then re-examine the key
      concepts and challenges of FBDD with particular emphasis on recent literature and
      our own experience from a substantial number of FBDD applications. Our opinion is
      that careful application of FBDD is living up to its promise of delivering high
      quality leads with good physical properties and that in future many drug
      molecules will be derived from fragment-based approaches.

PMID- 22459077
TI  - Modelling eating practices in non-fatal acute coronary syndrome or stroke
      development: a case/case-control study.
AB  - BACKGROUND AND AIMS: Although significant evidence exists regarding the role of
      specific foods and dietary patterns on the development of cardiovascular disease,
      the influence of eating practices has not been thoroughly examined and
      understood. The aim of the present work was to evaluate the independent role of
      eating practices on the likelihood of developing an acute coronary syndrome (ACS)
      or ischemic stroke. METHODS AND RESULTS: During 2009-2010, 1000 participants were
      enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive
      patients with a first ischemic stroke and 500 were population-based control
      subjects (250 age-sex matched one-for-one with ACS patients, and 250 age-sex
      matched one-for-one with stroke patients). Eating practices were evaluated using
      a special questionnaire. Socio-demographic, clinical, psychological, dietary and
      other lifestyle characteristics were also measured. After controlling for
      potential confounding factors, each 20 min prolongation of dinner-to-sleep time
      was associated with 10% lower likelihood of ischemic stroke (95%CI: 0.83-0.98).
      Furthermore, eating practices related to stress (i.e., eating while being
      stressed, eating while working at the same time, skipping a meal due to work
      obligations) were associated with higher likelihood of having an ACS. Finally,
      eating while watching television was associated with lower likelihood of having
      an ACS (OR: 0.46, 95%CI: 0.27-0.78) or stroke event (OR: 0.42, 95%CI: 0.23-0.77).
      CONCLUSION: Results of this work, present novel information, indicating the
      significance of eating practices, in addition to dietary patterns, regarding the
      development of coronary heart disease and stroke, and could be used in the
      primary prevention of CVD.

PMID- 22459078
TI  - Testing for syphilis during pregnancy.

PMID- 22459079
TI  - New EMA guideline for antimicrobial development.

PMID- 22459080
TI  - Diagnosis and treatment of pulmonary tuberculosis in patients with HIV.

PMID- 22459081
TI  - Diagnosis and treatment of pulmonary tuberculosis in patients with HIV.

PMID- 22459083
TI  - Syphilis: still a major cause of infant mortality.

PMID- 22459084
TI  - Syphilis: still a major cause of infant mortality.

PMID- 22459086
TI  - Antibiotics by bolus or infusion for bacterial meningitis?

PMID- 22459088
TI  - Jon Cohen: the rebirth of infectious diseases in the UK.

PMID- 22459089
TI  - Chronic unilateral conjunctivitis.

PMID- 22459090
TI  - Craniofacial morphology and sleep apnea in children with obstructed upper
      airways: differences between genders.
AB  - OBJECTIVES: To correlate sleep apnea with craniofacial characteristics and facial
      patterns according to gender. METHODS: In this prospective survey we studied 77
      male and female children (3-12 years old) with an upper airway obstruction due to
      tonsil and adenoid enlargement. Children with lung problems, neurological
      disorders and syndromes, obstructive septal deviation, previous orthodontic
      treatment, orthodontic surgeries or oral surgeries, or obesity were excluded.
      Patients were subjected to physical examinations, nasal fiberoptic endoscopy,
      teleradiography for cephalometric analysis, and polysomnography. Cephalometric
      analysis included the following skeletal craniofacial measurements: facial axis
      (FA), facial depth (FD), mandibular plane angle (MP), lower facial height (LFH),
      mandibular arch (MA), and vertical growth coefficient (VERT) index. RESULTS: The
      prevalence of sleep apnea was 46.75% with no statistical difference between
      genders. Among children with obstructive sleep apnea (Apneia Hypopnea Index - AHI
      >= 1) boys had higher AHI values than girls. A predominance of the dolichofacial
      pattern (81.9%) was observed. The following skeletal craniofacial measurements
      correlated with AHI in boys: FD (r(s)=-0.336/p=0.020), MP (r(s)=0.486/p=0.00),
      and VERT index (r(s)=-0.337/p=0.019). No correlations between craniofacial
      measurements and AHI were identified in girls. CONCLUSIONS: Craniofacial
      morphology may influence the severity of sleep apnea in boys but not in girls.

PMID- 22459091
TI  - Straightforward glycosylation of alcohols and amino acids mediated by ionic
      liquid.
AB  - Green glycosylation of functionalized alcohols and alpha-amino acids, using an
      ionic liquid as a recyclable solvent, was performed in one step directly from the
      unprotected monosaccharide under scandium triflate or ferric chloride catalysis.
      Pure alpha- and beta-glycosides could be obtained after specific enzymatic
      hydrolysis.

PMID- 22459092
TI  - Pharmacokinetics of mequindox and its metabolites in rats after intravenous and
      oral administration.
AB  - Pharmacokinetics of mequindox (MEQ) and its metabolites were determined in rats
      after intravenous (i.v.) and oral (p.o.) administration of MEQ at a single dose
      of 10 mg kg(-1) bodyweight. After both administrations, MEQ and five of its
      metabolites were quantified, except M4, whereas M1 and M2 were the predominant
      ones. The areas under the concentration-time curves (h ng mL(-1)) of MEQ, M1, M2,
      M3, M5 and M10 after i.v. administration were 7559+/-495, 6354+/-2761, 5586+/
      2337, 1034+/-160, 2370+/-791 and 1813+/-622, respectively, whereas after p.o.
      administration, remained as 2809+/-40, 4361+/-3544, 4351+/-1046, 1444+/-814,
      3864+/-305 and 1213+/-569, respectively. The elimination half-lives (h) of these
      compounds after i.v. administration were 3.48+/-0.80, 4.20+/-0.76, 6.25+/-2.41,
      4.77+/-1.54, 4.69+/-1.62 and 16.89+/-5.15, respectively, and were 3.21+/-0.40,
      3.66+/-1.06, 4.20+/-1.03, 8.91+/-5.99, 4.20+/-2.02 and 20.84+/-10.85 after p.o.
      administration, respectively. After p.o. administration, the bioavailability of
      MEQ was 37.16%. The results showed that MEQ was extensively metabolized in rats
      and rapidly absorbed after p.o. administration.

PMID- 22459093
TI  - Energetic cost of walking with increased step variability.
AB  - Step-by-step variations occur during normal human walking, induced in part by
      imperfect sensorimotor control and naturally occurring random perturbations.
      These effects might increase energy expenditure during walking, because they
      differ from the nominal preferred gait, which is typically the most economical,
      and because of the cost of making active feedback adjustments to maintain gait
      stability. We tested this hypothesis by artificially inducing greater step
      variability through visual perturbations from a virtual reality display, and
      measuring the effect on energy expenditure. Young healthy adult subjects (N=11)
      walked on a treadmill while viewing a virtual hallway, to which virtual
      perturbations were applied in fore-aft or medio-lateral directions. The greatest
      effect on gait was achieved with medio-lateral visual perturbations, which
      resulted in a 65% increase in step width variability and a 5.9% increase (both
      P<0.05) in net metabolic rate compared to walking without perturbations.
      Perturbations generally induced greater variability in both step width and (to a
      lesser degree) step length, and also induced slightly wider and (to a lesser
      degree) shorter mean steps. Each of these measures was found to correlate
      significantly with each other, regardless of perturbation direction and
      magnitude. They also correlated with metabolic rate (P<0.05 for each separate
      measure), despite explaining only a modest proportion of overall energetic
      variations (R(2)<0.40). Step variability increases with some gait disorders and
      with increasing age. Our results suggest that imperfect sensorimotor control may
      contribute to the increased metabolic cost of walking observed with such
      conditions.

PMID- 22459094
TI  - A comparison of submicrometer particle dose between Australian and Italian
      people.
AB  - Alveolar and tracheobronchial-deposited submicrometer particle number and surface
      area data received by different age groups in Australia are shown. Activity
      patterns were combined with microenvironmental data through a Monte Carlo method.
      Particle number distributions for the most significant microenvironments were
      obtained from our measurement survey data and people activity pattern data from
      the Australian Human Activity Pattern Survey were used. Daily alveolar particle
      number (surface area) dose received by all age groups was equal to 3.0 * 10(10)
      particles (4.5 * 10(2) mm(2)), varying slightly between males and females. In
      contrast to gender, the lifestyle was found to significantly affect the daily
      dose, with highest depositions characterizing adults. The main contribution was
      due to indoor microenvironments. Finally a comparison between Italian and
      Australian people in terms of received particle dose was reported; it shows that
      different cooking styles can affect dose levels: higher doses were received by
      Italians, mainly due to their particular cooking activity.

PMID- 22459095
TI  - Scalable GMP compliant suspension culture system for human ES cells.
AB  - Suspension bioreactors are an attractive alternative to static culture of human
      embryonic stem cells (hESCs) for the generation of clinically relevant cell
      numbers in a controlled system. In this study, we have developed a scalable
      suspension culture system using serum-free defined media with spinner flasks for
      hESC expansion as cell aggregates. With optimized cell seeding density and
      splitting interval, we demonstrate prolonged passaging and expansion of several
      hESC lines with overall expansion, yield, viability and maintenance of
      pluripotency equivalent to adherent culture. Human ESCs maintained in suspension
      as aggregates can be passaged at least 20 times to achieve over 1*10(13) fold
      calculated expansion with high undifferentiation rate and normal karyotype.
      Furthermore, the aggregates are able to differentiate to cardiomyocytes in a
      directed fashion. Finally, we show that the cells can be cryopreserved in serum
      free medium and thawed into adherent or suspension cultures to continue passaging
      and expansion. We have successfully used this method under cGMP or cGMP
      equivalent conditions to generate cell banks of several hESC lines. Taken
      together, our suspension culture system provides a powerful approach for scale-up
      expansion of hESCs under defined and serum-free conditions for clinical and
      research applications.

PMID- 22459096
TI  - Diphenyl diselenide ameliorates behavioral and oxidative parameters in an animal
      model of mania induced by ouabain.
AB  - Bipolar disorder (BD) is a common and severe mood disorder associated with higher
      rates of suicide and disability. Ouabain, a Na(+)/K(+)-ATPase inhibitor, induces
      behavioral changes in rats and has been used as a model of mania. The aim of this
      study was to investigate if diphenyl diselenide [(PhSe)(2)], an organoselenium
      compound with pharmacological properties, is effective against ouabain-induced
      hyperactivity and alterations in cerebral oxidative status of rats. Male Wistar
      rats were treated with a single dose of (PhSe)(2) (50 mg/kg, p.o.) 30 min before
      i.c.v. injection of ouabain (5 MUl, 10(-5) M) or with the mood stabilizer,
      lithium chloride (LiCl) (45 mg/kg, p.o.), twice a day, for 7 days before the
      administration of ouabain. Open-field locomotion was quantified after ouabain
      administration. Thiobarbituric acid reactive substances (TBARS), oxidatively
      modified proteins, tyrosine nitration, ascorbic acid and non-protein thiols
      (NPSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx) and glutathione reductase (GR) activities were determined in the
      whole brain. Ouabain increased locomotor activity in the open-field test and
      pretreatment with (PhSe)(2) or LiCl blocked this effect. In addition, ouabain
      increased lipid peroxidation and oxidatively modified proteins, demonstrated by a
      significant increase in TBARS levels and carbonyl content, which were attenuated
      by pretreatment with (PhSe)(2) or LiCl. The activities of SOD and CAT were
      increased by ouabain. LiCl was effective on preventing the increases of both
      enzyme activities, but (PhSe)(2) attenuated the ouabain effect in SOD activity.
      GPx and GR activities, ascorbic acid, NPSH and tyrosine nitration levels were not
      altered in all experimental groups. Similarly to LiCl, (PhSe)(2) produced an
      antimanic-like action, since it was effective against the locomotor hyperactivity
      elicited by ouabain. The results also indicated that (PhSe)(2) was effective
      against oxidative stress caused by ouabain in rats.

PMID- 22459097
TI  - Anterolateral kyphoplasty in the management of cervical spinal metastasis.
AB  - Management of spinal metastasis is still controversial and must take into account
      various parameters. The aim of this study is to report the technical feasibility
      of a less invasive anterior cervical balloon kyphoplasty for vertebral body
      reinforcement. Six consecutive patients with an osteolytic cervical metastasis,
      without neurologic compromise, and for whom a curative treatment was not
      indicated, were retrospectively reviewed. All patients underwent balloon
      kyphoplasty through a small anterolateral cervicotomy. Evaluation of the
      technique outcomes was clinical and radiologic with a systematic CT-scan. During
      the follow-up period (6 months average), neurologic examination was normal in all
      cases with reduced cervical pain and without reported loss of motion of the
      cervical spine. A cement leakage was noticed in two cases without clinical
      consequences. This less invasive procedure was feasible and provided satisfactory
      preliminary results. It can therefore be a valuable alternative in selected cases
      where a curative treatment is not indicated.

PMID- 22459098
TI  - Why publish a survey of orthopaedic scientific production from China?

PMID- 22459099
TI  - Retrieval analysis of squeaking ceramic implants: are there related specific
      features?
AB  - INTRODUCTION: Ceramic-on-ceramic total hip arthroplasty is routinely used for
      young and active patients with end stage of hip osteoarthritis. However,
      squeaking noise is a recently identified problem with such bearing surface. Many
      in vivo and in vitro studies have been conducted trying to find the potential
      causes of this phenomenon. However, we are not aware of any study analyzing
      retrieved ceramic implants for squeaking. HYPOTHESIS: Our primary hypothesis was
      that the surface analysis of retrieved ceramic implants with squeaking would
      present interesting deteriorations that could explain the squeaking noise.
      MATERIALS AND METHODS: Nine retrieved squeaking implants from ceramic-on-ceramic
      total hip arthroplasty that were retrieved for various reasons (two exclusively
      for squeaking, four for recurrent dislocation, one for aseptic loosening and two
      for instability) were analyzed. Implant positioning was calculated, macroscopic
      damages were noticed and microscopic roughness was analyzed. The retrieved
      implants were then tested on a hip simulator reproducing flexion/extension
      motions in several situations in lubricated and non-lubricated conditions in
      order to reproduce squeaking. RESULTS: Five cups were considered with borderline
      insufficient anteversion. Gross impingement damage was visible on seven implants.
      All the retrieved heads had visible metal transfer on their surface. Eight
      implants had visible stripe wear. Microscopic analysis showed roughness higher
      than six microns on the retrieved heads. Squeaking was reproduced in vitro in dry
      conditions. In lubricated conditions, squeaking did not occur for the retrieved
      hips. DISCUSSION: This retrieval analysis suggests that problems of cup
      orientation and design which can lead to impingement can generate lubrication
      problems because of metal transfer plus/minus stripe wear which is a common theme
      in ceramic-on-ceramic bearings that squeak.

PMID- 22459100
TI  - Neuropathic complications after 157 procedures of continuous popliteal nerve
      block for hallux valgus surgery. A retrospective study.
AB  - BACKGROUND: Continuous peripheral nerve block (CPNB), in particular at the
      popliteal fossa, is widely used in orthopedic surgery, allowing good
      postoperative analgesia. Possible neuropathic complications, however, remain
      poorly known. OBJECTIVE: To review the characteristics of peripheral neuropathy
      (PN) after sciatic CPNB at the popliteal fossa, estimating prevalence, severity,
      evolution and possible risk factors, especially those relating to the procedure.
      METHODS: Retrospective study of PN associated with popliteal fossa CPNB for
      hallux valgus surgery, between November 1st, 2005 and November 1st, 2009. All
      procedures were analyzed (type of anesthesia, approach, nerve location technique,
      number of procedures by operator) with, for each case of PN, analysis of clinical
      and electromyographic data. RESULTS: One hundred and fifty seven sciatic CPNBs
      were performed (92% women; mean age, 55 years). The approach was lateral (n=62),
      posterior (n=74) or unknown (n=21). Ultrasound guidance was combined to
      neurostimulation for 69 patients (44%). Three women (prevalence=1.91%), aged 19,
      24 and 65 years respectively, developed associated common superficial peroneal
      and sural nerve injury (2), axonal on electromyography, with motor (n=1) and/or
      sensory (n=3) residual dysfunction. DISCUSSION: The higher prevalence found in
      the present study than in the literature (0 to 0.5%) raises questions of
      methodological bias or technical problems. The common peroneal and sural nerves
      seem to be exposed, unlike the tibial. Several mechanisms can be suggested:
      anesthetic neurotoxicity, direct mechanical lesion, or tourniquet-related
      ischemia and conduction block. Further studies are necessary to determine the
      ideal anesthetic procedure. CONCLUSION: Patients should be informed of the
      potential risk, however rare, even during mild surgery. The best possible
      technique should be implemented, with reinforced surveillance.

PMID- 22459102
TI  - Multifractal characterisation of electrocardiographic RR and QT time-series
      before and after progressive exercise.
AB  - The scaling (fractal) characteristics of electrocardiograms (ECG) provide
      information complementary to traditional linear measurements (heart rate,
      repolarisation rate etc.) allowing them to discriminate signal changes induced
      pathologically or pharmacologically. Under such interventions scaling behaviour
      is described by multiple local scaling exponents and the signal is termed
      multifractal. Exercise testing is used extensively to quantify and monitor
      cardiorespiratory health, yet to our knowledge there has been no previous
      multifractal investigation of exercise-induced changes in heart rate dynamics.
      Ambulatory ECGs were acquired from eight healthy participants. Linear descriptive
      statistics and a parameterisation of multifractal singularity spectra were
      determined for inter-beat (RR) and intra-beat (QT) time-series before and after
      exercise. Multivariate analyses of both linear and multifractal measures
      discriminated between pre- and post-exercise periods and proportionally more
      significant correlations were observed between linear than between multifractal
      measures. Variance was more uniformly distributed over the first three principal
      components for multifractal measures and the two classes of measures were
      uncorrelated. Order and phase randomisation of the time-series indicated that
      both sample distribution and correlation properties contribute to
      multifractalilty. This exploratory study indicates the possibility of using
      physical exercise in conjunction with multifractal methodology as an adjunctive
      description of autonomically mediated modulation of heart rate.

PMID- 22459101
TI  - Joint perception after hip or knee replacement surgery.
AB  - INTRODUCTION: Knee and hip arthroplasties are recognized as being effective.
      However, subjects with a prosthetic joint rarely report returned sensation
      comparable to their native joint. HYPOTHESIS: Joint perception by patients
      following hip joint replacement is better than following knee replacement and in
      both cases this perception is directly related to the clinical results measured
      with currently validated scores. PATIENTS AND METHODS: Patient joint perception
      in prosthetic reconstruction was evaluated in 347 patients, 46 who underwent
      unicompartmental knee arthroplasty (UKA), 119 tricompartmental knee arthroplasty
      (TKA), 93 hip resurfacing (HR), and 89 total hip arthroplasty (THA). The
      subjects' joint perception, their satisfaction, and the WOMAC clinical score were
      recorded and compared. RESULTS: Joint perception was significantly worse for knee
      arthroplasties (TKA and UKA) compared to hip arthroplasties (THA or HR)
      (P<0.001). The WOMAC score was also significantly less favorable for knee
      arthroplasties than for hip arthroplasties (P<0.0001). However, there was no
      significant difference for the clinical scores between TKA and UKA as well as
      between HR and THA. Joint perception was strongly correlated with the WOMAC score
      for all groups (R(2)=0.951). DISCUSSION: No difference was found after more
      conservative surgeries such as HR or UKA compared to traditional arthroplasty
      procedures (THA or TKA). Demonstrating inferior results in comparison to the hip,
      knee arthroplasties deserve particular attention and can still be improved. The
      assessment of joint perception used in this study can be considered a valuable
      clinical tool that is strongly correlated to validated, but more complex to
      apply, clinical scores.

PMID- 22459103
TI  - Managing urinary incontinence through hand-held real-time decision support aid.
AB  - In this paper, we present an intelligent system for the diagnosis and treatment
      of urinary incontinence (UI) for males as well as females, called e-URIN. e-URIN
      is an intelligent system for diagnosis and treatment of urinary incontinence
      according to symptoms that are realized in one patient and usually recorded
      through his clinical examination as well as specific test results. The user
      friendly proposed intelligent system is accommodated on a hospital server
      supporting e-health tools, for use through pocket PCs under wireless connection
      as a decision support system for resident doctors, as well as an educational tool
      for medical students. It is based on expert system knowledge representation
      provided from urology experts in combination with rich bibliographic search and
      study ratified with statistical results from clinical practice. Preliminary
      experimental results on a real patient hospital database provide acceptable
      performance that can be improved using more than one computational intelligence
      approaches in the future.

PMID- 22459104
TI  - Circular Cone: a novel approach for protein ligand shape matching using modified
      PCA.
AB  - Nowadays in modern medicine, computer modeling has already become one of key
      methods toward the discovery of new pharmaceuticals. And virtual screening is a
      necessary process for this discovery. In the procedure of virtual screening,
      shape matching is the first step to select ligands for binding protein. In the
      era of HTS (high throughput screening), a fast algorithm with good result is in
      demand. Many methods have been discovered to fulfill the requirement. Our method,
      called "Circular Cone", by finding principal axis, gives another way toward this
      problem. We use modified PCA (principal component analysis) to get the principal
      axis, around which the rotation is like whirling a cone. By using this method,
      the speed of giving score to a pocket and a ligand is very fast, while the
      accuracy is ordinary. So, the good speed and the general accuracy of our method
      present a good choice for HTS.

PMID- 22459106
TI  - Bilateral response after unilateral subconjunctival bevacizumab injection in a
      child with Stevens-Johnson syndrome.
AB  - Bevacizumab is widely used for several ocular conditions, including age-related
      macular degeneration, diabetic retinopathy, corneal neovascularization,
      neovascular glaucoma, and retinopathy of prematurity. We describe a 14-year-old
      patient with Stevens-Johnson syndrome in whom subconjunctival injection of
      bevacizumab in one eye caused bilateral regression of corneal neovascularization.

PMID- 22459105
TI  - Comparison of Tono-Pen and Goldmann applanation tonometers for measurement of
      intraocular pressure in healthy children.
AB  - PURPOSE: To assess the agreement of intraocular pressure (IOP) measured with the
      Tono-Pen and the Goldmann applanation tonometer (GAT) in normal children and
      adolescents. METHODS: A total of 439 subjects from birth to <18 years of age
      without anterior segment anomalies or glaucoma had their IOP measured with the
      two instruments by separate, masked examiners in the office or under general
      anesthesia. RESULTS: On average, the Tono-Pen measured values slightly lower than
      the GAT for IOP <11 mm Hg and slightly higher than the GAT for IOP >11 mm Hg in
      the office setting. Using the average of GAT and Tono-Pen IOPs to estimate the
      true IOP, the average difference (GAT - Tono-Pen) was 0.4 mm Hg at IOP of 10 mm
      Hg and -3.0 mm Hg at IOP of 20 mm Hg. The 95% limits of agreement on the average
      difference between instruments were +/- 6.4 mm Hg in the office setting and +/-
      6.8 mm Hg under general anesthesia. Larger differences between instruments were
      found with younger age. Standard error of measurement with the Tono-Pen was 1.44
      mm Hg and 1.82 mm Hg for the office and anesthesia settings, respectively.
      Thicker corneas were associated with higher IOP with both the GAT and the Tono
      Pen. CONCLUSIONS: In normal children, average differences between IOP measured by
      Tono-Pen and GAT were small, although there was substantial test-retest
      variability. Younger age was associated with larger average differences, as was
      higher IOP in the office setting.

PMID- 22459107
TI  - Molecular prevalence of Cryptosporidium spp. in dairy calves in Southern states
      of India.
AB  - Dung samples were collected from dairy calves of south Indian states viz., Andhra
      Pradesh, Karnataka, Kerala, Tamil Nadu and union territory, Puducherry and are
      subjected to nested polymerase chain reaction (PCR) targeting 18S rRNA gene for
      detection of Cryptosporidium infection. Of the 459 dung samples screened 182 were
      found positive with a prevalence of 39.65%. Highest prevalence of Cryptosporidium
      was observed in Puducherry (86.67%) and lowest in Kerala (17.65%). Genotyping by
      PCR-restriction fragment length polymorphism (RFLP) and sequence analysis
      revealed the presence of all the four major Cryptosporidium species of cattle
      viz., Cryptosporidium andersoni, Cryptosporidium ryanae, Cryptosporidium parvum
      and Cryptosporidium bovis. C. andersoni was widely distributed in calves of Tamil
      Nadu, Karnataka and Puducherry whereas in Andhra Pradesh C. ryanae was the major
      species. Of the 64 samples subjected to PCR-RFLP, 39 (60.94%) could be classified
      as C. andersoni, 18 (28.13%) as C. ryanae, 4 (6.25%) as C. parvum and 3 (4.69%)
      were confirmed as C. bovis. The results were also confirmed by sequencing of 19
      Cryptosporidium DNA samples.

PMID- 22459108
TI  - Exposure to pasture borne nematodes affects individual milk yield in Swedish
      dairy herds.
AB  - The association between exposure to gastrointestinal nematode (GIN) parasitism,
      indicated by elevated individual optical density ratio (ODR) to Ostertagia
      ostertagi, and individual milk production was analysed in dairy cows. The
      multivariable analysis also accounted for other sources of variation than
      exposure to GIN parasitism. Intra- and inter-herd variation in parasite exposure
      was also evaluated. Organic and conventional herds located in south-east Sweden
      (13 herds per system) were visited during the housing period 2009-2010. Levels of
      all major pasture-borne helminths in Sweden (O. ostertagi, Fasciola hepatica and
      Dictyocaulus viviparus) were determined in bulk tank milk, cow milk and serum
      (only for O. ostertagi). Their specific antibodies were detected using three
      different ELISAs (Svanova Biotech) and the optical density of the sample was
      expressed as ODR. Positive cases of Dictyocaulus and Fasciola were seldom found.
      Variation in ODR in serum samples for Ostertagia was higher within herds than
      between herds. Correlations between ODR for Ostertagia in serum and milk
      parameters were significant and negative. In the multivariable analysis, two
      models were performed separating data from primiparous and multiparous cows.
      Results from mixed models showed that daily milk yield was significantly
      influenced by Ostertagia ODR for multiparous cows. No interactions were found
      between Ostertagia ODR values and herd type.

PMID- 22459109
TI  - Occurrence of pathogenic fungi to Amblyomma cajennense in a rural area of Central
      Brazil and their activities against vectors of Rocky Mountain spotted fever.
AB  - Two isolates of Beauveria bassiana and one of Purpureocillium lilacinum
      (=Paecilomyces lilacinus) were found infecting Amblyomma cajennense engorged
      females collected on horses (0.15% infection rate from a total of 1982 specimens)
      and another two isolates of P. lilacinum and one Metarhizium anisopliae detected
      in soils (2.1% from 144 samples) collected in typical pasture habitats of this
      tick in Central Brazil from October 2009 to March 2011. Fungi were isolated from
      soils with Rhipicephalus sanguineus as surrogate baits. No fungi were found in
      ticks or soils during the driest months (May to August). Testing pathogenicity of
      fungi all R. sanguineus females were killed regardless of the isolate and fungi
      sporulated abundantly on the cadavers. A. cajennense was less susceptible to
      infection with P. lilacinum within 20 days than R. sanguineus. All three fungal
      species probably act as natural antagonists of A. cajennense particularly in the
      rainy season and have interest for integrate control of vectors of Rocky Mountain
      spotted fever.

PMID- 22459110
TI  - Assessment of dietary supplementation with probiotics on performance, intestinal
      morphology and microflora of chickens infected with Eimeria tenella.
AB  - We evaluated the effects of dietary supplementation with different preparations
      of probiotics on the performance of broiler chickens experimentally infected with
      2 * 10(4) sporulated oocysts of Eimeria tenella at 14 days of age. Three hundred,
      day-old, Cobb-500 chicks, as hatched, were separated into 10 equal groups with
      three replicates. Two of the groups, one challenged with E. tenella oocysts and
      the other not, were given a basal diet and served as controls without medication.
      The other challenged groups were given the anticoccidial lasalocid (60 mg/kg) or
      Enterococcus faecium (5 * 10(8) or 5 * 10(9)cfu/kg feed), Bifidobacterium
      animalis (5 * 10(8)cfu/kg feed), Lactobacillus reuteri (5 * 10(8)cfu/kg feed),
      Bacillus subtilis (5 * 10(8)cfu/kg feed), or a multi-species probiotic mix at 5 *
      10(8) or 5 * 10(9)cfu/kg feed, respectively. The trial lasted 6 weeks. Individual
      body weight, feed intake per pen and feed conversion ratio values were recorded
      weekly, along with the extent of bloody diarrhea, excreta oocyst numbers and bird
      mortality. Caecal lesions were assessed and intestinal samples were taken for
      histopathological and bacteriological evaluation from ileum and caecum. Overall
      growth performance of chickens fed the multi-species probiotic mix at both levels
      was higher (P<0.05) compared to the infected control. Overall oocyst shedding was
      lowest (P<0.05) in the lasalocid supplemented group. Villous height was higher
      (P<0.05) in Bacillus supplemented groups compared to infected controls. The
      Lactobacillus supplemented group had the highest (P<0.05) numbers of both
      Lactobacillus and Bifidobacterium in ileum and caecum. In conclusion, dietary
      probiotics are promising for further investigation on improving intestinal health
      and growth performance of broiler chickens experimentally challenged with E.
      tenella.

PMID- 22459111
TI  - The comparative efficacy of abamectin, monepantel and an abamectin/derquantel
      combination against fourth-stage larvae of a macrocyclic lactone-resistant
      Teladorsagia spp. isolate infecting sheep.
AB  - Anthelmintic resistance by gastrointestinal nematodes of sheep continues to be an
      issue of global interest. While the recent introduction in some countries of one
      or two new anthelmintic classes (amino-acetonitrile derivatives [AAD] and
      spiroindoles [SI]) has been welcomed, it is important that there is no relaxation
      in parasite control and the management of drug resistance. Monepantel (an AAD)
      was the first new anthelmintic to be approved for use (New Zealand, 2009) and was
      followed a year later in the same country by a combination of derquantel (a SI)
      and abamectin. The present study determined the efficacy of the new anthelmintic
      products and abamectin against fourth-stage larvae of macrocyclic lactone
      resistant Teladorsagia spp. in lambs. Efficacies were calculated by comparing
      post-mortem nematode burdens of treated animals with those of untreated control
      sheep, and were 98.5, 86.3 and 34.0% for monepantel, abamectin/derquantel and
      abamectin, respectively. The nematode burdens of monepantel- and
      abamectin/derquantel-treated sheep were significantly lower than those sheep
      treated with abamectin and the untreated controls. Similarly, the burden of the
      monepantel group was significantly lower than that of the abamectin/derquantel
      group. These findings provide an opportunity to reinforce the recommendation that
      farmers and animal health advisors need to know the resistance status of nematode
      populations on subject farms to ensure effective control programs are designed
      and implemented. Such control programs should include an appropriate choice of
      anthelmintic(s), monitoring parasite burdens for correct timing of treatments,
      and pasture management to reduce larval challenge balanced with the maintenance
      of drug-susceptible populations in refugia.

PMID- 22459112
TI  - Preference for condensed tannins by sheep in response to challenge infection with
      Haemonchus contortus.
AB  - Herbivores prefer feeds that supply required nutrients and avoid those with
      excess nutrients and plant secondary compounds (PSC). Nevertheless, PSC such as
      condensed tannins can provide beneficial medicinal effects to herbivores as they
      act against infective diseases such as parasitism. The objectives of this study
      were to determine: (1) if parasitized lambs increased preference for a tannin
      rich feed after they experienced the beneficial antiparasitic effects of
      condensed tannins relative to parasitized lambs that did not experience such
      benefits, and (2) if preference for the tannin-rich feed in the former group
      decreased when parasite burdens subsided. Twenty two lambs were familiarized with
      beet pulp and beet pulp+8% quebracho tannins (beet pulp+tannins) and choices were
      given between the two feeds (initial preference tests). Subsequently, all animals
      were dosed with 10,000 L(3) stage larvae of Haemonchus contortus. Twenty-two days
      later, animals were exposed to beet pulp (Control group; n=11) or beet
      pulp+tannins (Treatment group; n=11) during 24 d. After exposure (during a
      parasitic infection) animals in both groups were given choices between the two
      feeds. Lastly, animals in both groups received an antiparasitic drench and were
      again given a choice between both feeds (after a parasitic infection). Lambs
      preferred beet pulp to beet pulp+tannins throughout the study (P<0.001) and no
      difference in preference for the tannin-rich feed was detected between groups
      during initial preference tests (P>0.05). However, during a parasitic infection,
      intake of and preference for the tannin-rich feed was higher for lambs that
      experienced the beneficial effects of condensed tannins while parasitized
      (Treatment) than for lambs that did not (Control) (P<0.05). When parasitic
      infections were terminated by chemotherapy, differences between groups
      disappeared (P>0.05). Preference by the Treatment group for the tannin-rich feed
      was lower after than during a parasite infection (P<0.05). In contrast,
      preference by the Control group did not change during these periods (P>0.05).
      Lambs in the Treatment group displayed lower FEC than lambs in the Control group
      (Group * Sampling Date; P<0.05). These results show lambs learned about the
      antiparasitic effects of condensed tannins and increased their preference for the
      tannin-rich feed, which subsided after chemotherapy, indicating preference was
      due to parasite infection. These findings suggest management that allows animals
      to select tannin-rich feeds can enable parasitized animals to self-medicate.

PMID- 22459113
TI  - Limitations on accurate shape determination using amplitude modulation atomic
      force microscopy.
AB  - The limitations of amplitude modulation atomic force microscopy to accurately
      measure the shape or form of features are investigated. The control feedback loop
      and the dynamics of the cantilever limit the response time of the atomic force
      microscope. Simply subtracting appropriately scaled amplitude (error) signal from
      the topography data significantly improves the accuracy of the data and can
      correct for the slow response time of the feedback loop. Two mechanisms were
      found to induce topographic errors independent of scan speed. The first is the
      change in tip/surface interaction at a step edge observed by comparison with
      results from a 'virtual' sample. The second is due to friction between the probe
      and sample but only for a specifically oriented step edge determined by the
      direction of oscillation of the cantilever.

PMID- 22459114
TI  - Sub-nanometer free electrons with topological charge.
AB  - The holographic mask technique is used to create freely moving electrons with
      quantized angular momentum. With electron optical elements they can be focused to
      vortices with diameters below the nanometer range. The understanding of these
      vortex beams is important for many applications. Here, we produce electron vortex
      beams and compare them to a theory of electrons with topological charge. The
      experimental results show excellent agreement with simulations. As an immediate
      application, fundamental experimental parameters like spherical aberration and
      partial coherence are determined.

PMID- 22459115
TI  - Micromagnetic study of flux-closure states in Fe dots using quantitative Lorentz
      microscopy.
AB  - A micromagnetic study of epitaxial micron-sized iron dots is reported through the
      analysis of Fresnel contrast in Lorentz Microscopy. Their use is reviewed and
      developed through analysis of various magnetic structures in such dots. Simple
      Landau configuration is used to investigate various aspects of asymmetric Bloch
      domain walls. The experimental width of such a complex wall is first derived and
      its value is discussed with the help of micromagnetic simulations. Combination of
      these two approaches enables us to define what is really extracted when
      estimating asymmetric wall width in Lorentz Microscopy. Moreover, quantitative
      data on the magnetization inside the dot is retrieved using phase retrieval as
      well as new information on the degrees of freedom of such walls. Finally, it is
      shown how the existence and the propagation of a surface vortex can be
      characterized and monitored. This demonstrates the ability to reach a magnetic
      sensitivity a priori hidden in Fresnel contrast, based on an original image
      treatment and backed-up by the evaluation of contrasts obtained from
      micromagnetic simulations.

PMID- 22459116
TI  - Simultaneous and independent adaptive correction of spherical and chromatic
      aberration using an electron mirror and lens combination.
AB  - We present a theoretical analysis of an electrostatic triode mirror combined with
      an einzel lens for the correction of spherical and chromatic aberration. We show
      that this device adaptively corrects spherical and chromatic aberration
      simultaneously and independently. Chromatic aberration can be compensated over a
      relative range of -38% to +100%, and spherical aberration over +/-100% range. We
      compare the analytic calculation with a numerical simulation and show that the
      two descriptions agree to within 5% in the relevant operating regime of the
      device.

PMID- 22459117
TI  - Discrete tomography of demanding samples based on a modified SIRT algorithm.
AB  - The 3D structure of three particularly challenging samples was reconstructed by
      electron tomography. Due to sample limitations resulting in a large missing wedge
      and large tilt increments respectively the 3D structure could not be
      reconstructed by standard iterative algorithms; even a recently developed
      discrete algorithm failed until the input parameters for discrete reconstruction
      were improved. These challenges were addressed by adding a mask in each step of
      the preceding standard iterative reconstruction, setting all voxels known to be
      vacuum as zero, thus improving the segmentation and the 3D starting model. The
      position of these vacuum voxels is obtained from TEM images or other measurement
      data.

PMID- 22459118
TI  - Structure projection reconstruction from through-focus series of high-resolution
      transmission electron microscopy images.
AB  - A structure projection reconstruction method based on contrast transfer function
      correction of through-focus series of high-resolution transmission electron
      microscopy images is presented. In this method, defocus values are determined by
      evaluating phase similarities of the pixels on the Fourier transforms of the
      images after correction using trial defocus values. Two-fold astigmatism is also
      determined, by measuring focus variation along different directions. Each image
      in the series is corrected for the effects of contrast transfer function and then
      combined into a structure projection image. The method works for both crystalline
      and non-crystalline objects. Test results with experimental images are presented.
      Influences of experimental parameters for imaging and effects of crystal
      thickness on reconstruction are discussed.

PMID- 22459119
TI  - Optimization of Q-factor of AFM cantilevers using genetic algorithms.
AB  - Micro cantilever beams have been intensively used in sensing applications
      including to scanning profiles and surfaces where there resolution and imaging
      speed are critical. Force resolution is related to the Q-factor. When the micro
      cantilever operates in air with small separation gaps, the Q-factor is even more
      reduced due to the squeeze-film damping effect. Thus, the optimization of the
      configuration of an AFM micro-cantilever is presented in this work with the
      objective of improving its Q-factor. To accomplish this task, we propose the
      inclusion of holes as breathing chimneys in the initial design to reduce the
      squeeze-film damping effect. The evaluation of the Q-factor was carried out using
      finite element model, which is implemented to work together with the squeeze-film
      damping model. The methodology applied in the optimization process was genetic
      algorithms, which considers as constraints the maximum allowable stress,
      fundamental frequency and spring constant with respect to the initial design. The
      results show that the optimum design, which includes holes with an optimal
      location, increases the Q-factor almost five times compared to the initial
      design.

PMID- 22459120
TI  - PseAAC-Builder: a cross-platform stand-alone program for generating various
      special Chou's pseudo-amino acid compositions.
AB  - The pseudo-amino acid composition has been widely used to convert complicated
      protein sequences with various lengths to fixed length digital feature vectors
      while keeping considerable sequence order information. However, so far the only
      software available to the public is the web server PseAAC
      (http://www.csbio.sjtu.edu.cn/bioinf/PseAAC), which has some limitations in
      dealing with large-scale datasets. Here, we propose a new cross-platform stand
      alone software program, called PseAAC-Builder (http://www.pseb.sf.net), which can
      be used to generate various modes of Chou's pseudo-amino acid composition in a
      much more efficient and flexible way. It is anticipated that PseAAC-Builder may
      become a useful tool for studying various protein attributes.

PMID- 22459121
TI  - The probability of undetected wild poliovirus circulation after apparent global
      interruption of transmission.
AB  - The Global Polio Laboratory Network maintains active surveillance for circulating
      live polioviruses by obtaining and testing stool samples from patients with acute
      flaccid paralysis. However, most poliovirus infections occur with no symptoms,
      and questions remain about the probability of undetected wild poliovirus (WPV)
      circulation after the apparent interruption of WPV transmission in different
      populations. In the context of making decisions about the timing of oral
      poliovirus vaccine cessation following global eradication of WPV, policy-makers
      need an understanding of this probability as a function of time. Prior modeling
      of the probability of undetected circulation relied on relatively simple models
      and assumptions, which limits extrapolation to current conditions. In this
      analysis, the authors revisit the topic and highlight important considerations
      for policy-makers related to the impact of initial conditions and seasonality and
      emphasize the need to focus on appropriate characterization of conditions in the
      last likely reservoirs of the virus. The authors conclude that the probability of
      undetected WPV circulation may vary significantly for different poliovirus
      serotypes, places, and conditions, which suggests that achieving the same level
      of confidence about the true interruption of WPV transmission will require
      different periods of time for different situations.

PMID- 22459123
TI  - No significant squeaking in total hip arthroplasty: a series of 413 hips in the
      Asian people.
AB  - Some studies have reported the presence of audible squeaking in ceramic-on
      ceramic total hip arthroplasty (THA), and several factors such as implant
      malposition or poor soft tissue recovery have been described as the cause. Our
      purpose was to determine the squeaking rate in the Asian population with a
      consecutive series of ceramic-on-ceramic THA. From 2003 to 2009, 413 THAs were
      performed by a single surgeon using a minimally invasive modified anterior
      lateral approach. Using both questionnaire and physical examination, no squeaking
      was identified in any cases with a minimum of 2-year follow-up. Complications
      occurred in 4 patients. The results of this study suggested squeaking phenomenon
      after ceramic-on-ceramic THA may be eliminated.

PMID- 22459122
TI  - Interactions between genome-wide significant genetic variants and circulating
      concentrations of insulin-like growth factor 1, sex hormones, and binding
      proteins in relation to prostate cancer risk in the National Cancer Institute
      Breast and Prostate Cancer Cohort Consortium.
AB  - Genome-wide association studies (GWAS) have identified many single nucleotide
      polymorphisms (SNPs) associated with prostate cancer risk. There is limited
      information on the mechanistic basis of these associations, particularly about
      whether they interact with circulating concentrations of growth factors and sex
      hormones, which may be important in prostate cancer etiology. Using conditional
      logistic regression, the authors compared per-allele odds ratios for prostate
      cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating
      concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth
      factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol
      glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases
      and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After
      allowing for multiple testing, none of the SNPs examined were significantly
      associated with growth factor or hormone concentrations, and the SNP-prostate
      cancer associations did not differ by these concentrations, although 4
      interactions were marginally significant (MSMB-rs10993994 with androstenedione
      (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003);
      11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449
      with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that
      associations between GWAS-identified SNPs and prostate cancer are modified by
      circulating concentrations of IGF-1, sex hormones, or their major binding
      proteins.

PMID- 22459125
TI  - Dynamic measurements of hip movement in deep bending activities after total hip
      arthroplasty using a 4-dimensional motion analysis system.
AB  - Although deep hip bending activities are often required in Asian populations
      because of traditional lifestyles and religious practices, few have examined the
      required hip range of motion (ROM) in these activities after total hip
      arthroplasty (THA). We performed postoperative motion analysis to evaluate the
      differences in required ROMs between Japanese-style and Western-style deep hip
      bending activities, to investigate whether prosthetic impingement would occur
      during these activities and to clarify the necessity for precautions in these
      activities after THA. Japanese-style activities did not require larger hip ROMs
      than Western-style ones, and all required hip flexion angles were less than 120
      degrees . Prosthetic impingement was not observed, with a safety margin 10
      degrees  or higher until impingement in any directions of flexion, adduction, or
      internal rotation for any activities. Thus, particular postoperative precautions
      for Japanese-style activities are not required.

PMID- 22459124
TI  - Minimally invasive total knee arthroplasty improves early knee strength but not
      functional performance: a randomized controlled trial.
AB  - A prospective, randomized investigation compared early clinical outcomes of total
      knee arthroplasty (TKA) using conventional or minimally invasive surgical (MIS)
      approaches (n = 44). Outcome measures included isometric quadriceps and
      hamstrings strength, quadriceps activation, functional performance, knee pain,
      active knee range of motion, muscle mass, the Short Form-36, and Western Ontario
      and McMaster University Osteoarthritis Index, assessed preoperatively and 4 and
      12 weeks after TKA. Four weeks after TKA, the MIS group had greater hamstring
      strength (P = .02) and quadriceps strength (P = .07), which did not translate to
      differences in other outcomes. At 12 weeks, there were no clinically meaningful
      differences between groups on any measure. Although MIS may lead to faster
      recovery of strength in patients undergoing TKA, there was no benefit on longer
      term recovery of strength or functional performance.

PMID- 22459126
TI  - Outpatient unicompartment knee arthroplasty with indwelling femoral nerve
      catheter.
AB  - Contemporary multimodal anesthesia regimens allow the performance of
      unicompartment knee arthroplasty (UKA) on an outpatient basis. Our initial pilot
      experience is presented using a continuous femoral nerve block as an adjunct for
      24 patients classified as American Society of Anesthesiology class 1 (14 men, 10
      women; median age, 56 years; range, 46-72 years). After minimally invasive UKA,
      patients documented their pain and oral medication use while at home for the
      first 5 days. Adverse events, medication adverse effects, and the amount of
      infused ropivacaine were recorded. Median pain scores for the first 3 days were
      1, 2, and 2 (at rest) and 4, 5, and 3 (during physical therapy). Eighteen
      patients (75%) required less than 4 mg oral hydromorphone/d. Of the 18, 10 (42%)
      did not require supplemental oral opioids. The median catheter use was 3 days.
      Our results suggest that with careful patient selection and adequate teaching,
      continuous femoral nerve blocks may be used as part of a multimodal pain regimen
      to assist the delivery of outpatient UKA with high patient satisfaction.

PMID- 22459127
TI  - Global gene expression profiling confirms the molecular fidelity of primary tumor
      based orthotopic xenograft mouse models of medulloblastoma.
AB  - We previously showed that primary tumor-based orthotopic xenograft mouse models
      of medulloblastoma replicated the histopathological phenotypes of patients'
      original tumors. Here, we performed global gene expression profiling of 11
      patient-specific xenograft models to further determine whether the xenograft
      tumors were molecularly accurate during serial subtransplantations in mouse
      brains and whether they represented all the molecular subtypes of medulloblastoma
      that were recently described. Analysis of the transcriptomes of 9 pairs of
      matched passage I xenografts and patients' tumors revealed high correlation
      coefficients (r(2) > 0.95 in 5 models, > 0.9 in 3 models, and > 0.85 in 1 model)
      and only identified 69 genes in which expressions were altered (FDR = 0.0023).
      Subsequent pair-wise comparisons between passage I, III, and V xenografts from
      the 11 models further showed that no dramatic alterations were introduced (r(2) >
      0.9 in 8 models and > 0.8 in 3 models). The genetic abnormalities of each model
      were then identified through comparison with control RNAs from 5 normal cerebella
      and 2 fetal brains. Hierarchical clustering using 3 previously published
      molecular signatures showed that our models span the whole spectrum of molecular
      subtypes, including SHH (n = 2), WNT (n = 2), and the most recently identified
      group C (n = 4) and group D (n = 3). In conclusion, we demonstrated that the 11
      orthotopic medulloblastoma xenograft models were molecularly faithful to the
      primary tumors, and our comprehensive collection of molecularly distinct animal
      models should serve as a valuable resource for the development of new targeted
      therapies for medulloblastoma.

PMID- 22459129
TI  - [Single-port gastric bypass: technical details of a new approach].

PMID- 22459128
TI  - Treatment-related myelodysplasia in patients with primary brain tumors.
AB  - Treatment-related myelodysplastic syndrome (t-MDS) and treatment-related acute
      myelogenous leukemia (t-AML) represent rare secondary events in patients with
      primary tumors of the nervous system and predominantly affect those treated with
      alkylating agents or topoisomerase II inhibitors. Temozolomide has become the
      standard chemotherapeutic agent for malignant gliomas. The emergence of this
      alkylating agent with little acute toxicity or cumulative myelosuppression has
      led to off-label protracted chemotherapy for many patients with malignant and
      even low-grade infiltrative gliomas, raising concern for increased risk of t
      MDS/t-AML in the few long-term survivors. On the basis of an extensive literature
      search, we provide a discussion of epidemiology, pathogenesis, clinical
      presentation, diagnosis, and therapy of these disorders. t-MDS/t-AML remain rare
      complications of chemotherapy in patients with primary brain tumors, and the vast
      majority of patients die of their primary neoplasm. Prospective randomized
      studies with long-term follow-up are required to accurately assess the risk of t
      MDS/t-AML; however, unless survival in the most common gliomas substantially
      increases, t-MDS/t-AML incidence will likely remain low in this patient
      population.

PMID- 22459130
TI  - Effect of charcoal types and grilling conditions on formation of heterocyclic
      aromatic amines (HAs) and polycyclic aromatic hydrocarbons (PAHs) in grilled
      muscle foods.
AB  - Grilling muscle foods involves high temperatures that lead to production of
      cooking toxicants, such as heterocyclic aromatic amines (HAs) and polycyclic
      aromatic hydrocarbons (PAHs). To obtain realistic exposure levels of these two
      groups of mutagens analyses of the same samples using similar
      separation/detection techniques were performed. HAs and PAHs were quantified in
      well-done meat and fish samples grilled with wood and coconut shell charcoal at
      200 degrees C. Quantitative HAs and PAHs profiles were different for beef and
      salmon using the same type of charcoal. Higher levels of HAs and PAHs were found
      in salmon samples. No significant differences were observed for HAs and PAHs in
      beef samples grilled with both charcoal types, whereas salmon grilled with
      coconut shell charcoal presented significantly lower amounts of HAs and PAHs than
      salmon grilled with usual wood charcoal. Continuous barbecuing with the same
      charcoal shown that combustion of fat that dropped along the grilling period
      contributed to higher formation of HAs and PAHs. Special attention must be given
      to the intake of barbecued foods since high amounts of HAs and PAHs can be taken
      in a single meal.

PMID- 22459131
TI  - Chaperone-dependent mechanisms for acid resistance in enteric bacteria.
AB  - The extremely acidic environment of the mammalian stomach not only serves to
      facilitate food digestion but also acts as a natural barrier against infections
      of food-borne pathogens. Many pathogenic bacteria, such as enterohemorrhagic
      Escherichia coli, can breach this host defense and cause severe diseases. These
      pathogens have evolved multiple intricate strategies to overcome the bactericidal
      activity of acids. In particular, recent studies have uncovered the central roles
      of two periplasmic chaperones, HdeA and HdeB, in protecting enteric bacteria from
      extremely acidic conditions. Here, we review recent advances in the understanding
      of the acid resistance mechanisms of Gram-negative bacteria and focus on the
      mechanisms of HdeA and HdeB in preventing acid-induced protein aggregation and
      facilitating protein refolding following pH neutralization.

PMID- 22459132
TI  - Accountable care organizations and ESRD: the time has come.
AB  - Accountable care organizations (ACOs) are a newly proposed vehicle for improving
      or maintaining high-quality patient care while controlling costs. They are meant
      to achieve the goals of the Medicare Shared Savings Program mandated by the
      Patient Protection and Affordable Care Act (PPACA) of 2010. ACOs are voluntary
      groups of hospitals, physicians, and health care teams that provide care for a
      defined group of Medicare beneficiaries and assume responsibility for providing
      high-quality care through defined quality measures at a cost below what would
      have been expected. If an ACO succeeds in achieving both the quality measures and
      reduced costs, the ACO will share in Medicare's cost savings. Health care for
      patients with end-stage renal disease is complex due to multiple patient comorbid
      conditions, expensive, and often poorly coordinated. Due to the unique needs of
      patients with end-stage renal disease receiving dialysis, ACOs may be unable to
      provide the highly specialized quality care these patients require. We discuss
      the benefits and risks of a renal-focused ACO for dialysis patients, as well as
      the kidney community's prior experience with an ACO-like demonstration project.

PMID- 22459133
TI  - [Medical teaching in France: a transitory situation?].

PMID- 22459134
TI  - Physical and rehabilitation medicine (PRM) care pathways: "patients after total
      hip arthroplasty".
AB  - This document is part of a series of documents designed by the French Physical
      and Rehabilitation Medicine Society (SOFMER) and the French Federation of PRM
      (FEDMER). These documents describe the needs for or a specific type of patients;
      PRM care objectives, human and material resources to be implemented, chronology
      as well as expected outcomes. "Care pathways in PRM" is a short document designed
      to enable the reader (physicians, decision-maker, administrator, lawyer or
      finance manager) to quickly apprehend the needs of these patients and the
      available therapeutic care structures for proper organization and pricing of
      these activities. Patients after total hip arthroplasty are classified into three
      care sequences and two clinical categories, each one being treated with the same
      six parameters according to the International Classification of Functioning,
      Disability and Health (WHO), while taking into account personal and environmental
      factors that could influence the needs of these patients.

PMID- 22459135
TI  - Health care policy debates: let's bring back civility.

PMID- 22459136
TI  - Research support in doctoral-granting schools of nursing: a decade later.
AB  - Many nursing schools invest resources in offices to support research efforts and
      to strengthen research programs for external funding. This article will describe
      the resources available for research support in schools of nursing with doctoral
      degree-granting programs. Using a descriptive survey design, invitations and
      links to the online survey were sent to deans of nursing schools offering
      doctoral degrees as identified by the American Association of Colleges of
      Nursing. Response rate was 70.6% (120/170 eligible institutions), and 75% had a
      research office. Presence of a research office was associated with being in an
      academic health sciences center, being located in a public institution, and
      offering a doctor of philosophy (PhD) program. In 2009-2010, the average budget
      for the research offices was $390,000. Research offices were staffed by a
      director (88.6%), a grant administrator (78%), a statistician (74%), and a
      clerical staff (58.6%) and provided an array of services including grant support,
      scholarly support, and faculty development services. Nursing schools provided
      various support services for research productivity. Of those schools reporting
      that they had a research office, 59% had received National Institutes of Health
      (NIH) funding in the past year. Greater NIH funding was associated with those
      research offices employing more staff and offices existing for longer periods.

PMID- 22459137
TI  - From daunting task to new beginnings: bachelor of science in nursing curriculum
      revision using the new essentials.
AB  - Undergraduate curriculum revision is a daunting task, particularly when new
      accreditation criteria clearly call for substantive changes in how baccalaureate
      generalist nurses are educated. Using the nine essentials of The Essentials of
      Baccalaureate Education for Professional Nursing Practice (American Association
      of Colleges of Nursing, 2008) and the 109 Essential outcomes, the University of
      Kansas School of Nursing undergraduate faculty employed three phases of change:
      (a) understanding, (b) analysis, and (c) design to create an innovative
      curriculum. Theoretical influences from E. M. Rogers' (2003) Diffusion of
      Innovations theory, W. Bridges' (2009) work with transitions, and concepts of
      ownership guided the revision process. Strategies, such as gap analysis, nominal
      group technique, and word clouds, facilitated faculty transition from the ending
      of the old curriculum to ownership and beginning of the new curriculum. Inductive
      methods of faculty perceptions of ideal graduate characteristics and clustering
      of themes in the 109 Essential outcomes produced five themes: (a)
      communication/professional development, (b) evidence-based practice, (c)
      leadership/management, (d) nursing across the lifespan, and (e) population-based
      health care. A Q-Sort of the Essentials placed all 109 essential outcomes under
      each of these categories. Essential outcomes within these categories were then
      interpreted as data points and used as the basis for course design and
      accompanying credit allocation. A variety of research, theory, and
      interpersonally sensitive approaches yielded an innovative curriculum reflecting
      the Essentials and "new beginnings" for the undergraduate faculty.

PMID- 22459138
TI  - Faculty practice: is it scholarly activity?
AB  - "Nursing is a science that is applied in practice and is deeply rooted in a
      fundamental commitment to meeting the health needs of people regardless of their
      life circumstances" (J. Edwards, 2002). How can the role of nursing educator be
      any different? New requirements from accrediting bodies, state nursing boards,
      and other authorities ensure we are meeting the needs of this generation of
      nursing students. How then do we protect our professional practice within the
      demands of the university? To answer this question, we will examine the available
      literature as it relates to nursing, education, professional practice,
      scholarship, and faculty evaluation. Implications for the nursing profession and
      education include defining faculty practice within the mission of the university,
      enhancing the working relationship between schools of nursing and clinical sites,
      and developing faculty practice guidelines with a clear definition of
      scholarship. The definition of scholarship that we recommend that meets the needs
      of practice disciplines is the definition of scholarship by Ernest Boyer (1990),
      specifically the scholarship of application. As defined by Boyer, the scholarship
      of application "...is one that both applies and contributes to human knowledge"
      (p. 23).

PMID- 22459139
TI  - Lesbian, gay, bisexual, transgendered, or intersexed content for nursing
      curricula.
AB  - There has been limited identification of core lesbian, gay, bisexual,
      transgendered, or intersexed (LGBTI) experience concepts that should be included
      in the nursing curricula. This article addresses the gap in the literature. To
      move nursing toward the goals of health equity and cultural humility in practice,
      education, and research, nursing curricula must integrate core LGBTI concepts,
      experiences, and needs related to health and illness. This article reviews LGBTI
      health care literature to address the attitudes, knowledge, and skills needed to
      address curricular gaps and provide content suggestions for inclusion in nursing
      curricula. Also considered is the need to expand nursing students' definition of
      diversity before discussing the interplay between nurses' attitudes and
      culturally competent care provided to persons who are LGBTI. Knowledge needed
      includes a life span perspective that addresses developmental needs and their
      impact on health concerns throughout the life course; health promotion and
      disease prevention with an articulation of unique health issues for this
      population; mental health concerns; specific health needs of transgender and
      intersex individuals; barriers to health care; interventions and resources
      including Internet sites; and legal and policy issues. Particular assessment and
      communication skills for LGBTI patients are identified. Finally, there is a
      discussion of didactic, simulation, and clinical strategies for incorporating
      this content into nursing curricula at the undergraduate and graduate levels.

PMID- 22459140
TI  - Incorporating national priorities into the curriculum.
AB  - There are many aspects of care that need an overhaul to function safely,
      efficiently, and effectively. There needs to be a new culture in health care that
      focuses on safety and quality, and it will take many shareholders working
      together to make this possible. The National Priorities Partnership is a group of
      28 national organizations from across the health care spectrum collaborating to
      change the health care delivery system. The Partners acknowledged four challenges
      individuals face in the current U.S. system: harm, disparity, disease burden, and
      waste. To meet these challenges and improve performance, the Partners identified
      six priorities: patient and family engagement, population health, safety, care
      coordination, palliative and end-of-life care, and overuse (National Priorities
      Partnership). It is hopeful that when put into practice, these essentials will
      have a significant impact on improving health care. It comes down to creating a
      culture of safety and quality. This culture should start during entry-level
      education for health care providers, such as nursing schools. The priorities and
      goals provide a framework that can be incorporated into the curriculum so future
      nurses are aware of the issues and challenges in health care today. Each
      challenge needs evidence-based strategies for achieving the desired results. It
      is time to create a culture of safety and quality in health care.

PMID- 22459141
TI  - Patient safety manifesto: a professional imperative for prelicensure nursing
      education.
AB  - Nurses in practice and students in training often fear hurting a patient or doing
      something wrong. Experienced nurses have developed assessment skills and clinical
      intuition to recognize and intervene to prevent patient risk and harm. Beginning
      nursing students have not yet had the opportunity to develop an awareness of
      patient risk, safety concerns, or a clear sense of their accountability in the
      nurse role as the primary advocate for patient safety. In this Safety Manifesto,
      the authors call for educators to critically review their prelicensure curricula
      for inclusion of teaching and learning activities that are focused on patient
      safety and offer recommendations for curricular changes with an emphasis on
      integration of instructional strategies that develop students' skills for
      clinical reasoning and judgment.

PMID- 22459142
TI  - Achieving transformational change: using appreciative inquiry for strategic
      planning in a school of nursing.
AB  - To achieve transformational change, a transformational approach is needed. The
      Appreciative Inquiry (AI) summit is a method that has been used to achieve
      transformational change in business for at least 20 years, but this innovative
      alternative approach is unknown to nursing. At the University of Virginia School
      of Nursing, an AI Summit was designed to bring all staff, faculty, student
      representatives, and members of the community together to rewrite the school's
      strategic plan. New connections within the school, the university, and the
      community were made when 135 participants engaged in the appreciative, 4-step AI
      process of discovering, dreaming, designing, and creating the school's future.
      During the summit, 7 strategic teams formed to move the school toward the best
      possible future while building on the existing positive core. This article
      describes 10 steps needed to design an AI summit and implications for using this
      method at other schools of nursing.

PMID- 22459143
TI  - Case-based online modules to teach graduate-level nursing students about
      complementary and alternative medical therapies.
AB  - We integrated complementary and alternative medicine (CAM)-related content into
      selected core courses in our master's-level curriculum. To facilitate students'
      application of the content, we developed evidence-based online case studies and
      evaluated their effectiveness by comparing students' pretest and posttest scores
      on multiple-choice quizzes. Findings suggest that evidence-based online case
      studies are an effective strategy for teaching graduate nursing students about
      the clinical issues surrounding patients' use of CAM therapies.

PMID- 22459144
TI  - Self-reflection in nursing.

PMID- 22459145
TI  - Nurse educators establishing new venues in global nursing education.
AB  - Nurses represent the largest number of health care workers worldwide, but they
      are currently underutilized for global health practices. This may be due to the
      fact that global health programs are not incorporated in nursing education in
      many countries. The World Health organization (WHO) recognized the importance of
      building capacity and having well-prepared nurses who are able to exchange
      knowledge and expertise worldwide, but did not offer practical solutions. A
      nursing Super course recognizes the gap between what WHO advocates for and what
      needs to be done in nursing education to achieve well prepared nurses. A solution
      suggested is to develop well-structured contents that are applicable and can be
      shared among nursing programs worldwide. A nursing Supercourse is proposed to
      provide lectures prepared by expert nursing educators and researchers in global
      health. The nursing Supercourse has emerged from the parent Supercourse that is a
      virtual library of lectures developed by world experts in public health and
      medicine. It represents a global library of over 4,300 public health and medical
      lectures and a network of over 56,000 public health professionals in 174
      countries of the world. These lectures are written in different languages,
      prepared in easy format, and can be accessed through the internet. In other words
      does not require the usage of any advanced technology. The Supercourse
      educational technology has been used successfully in Epidemiology education
      focusing on multiple topics in public health such as non- communicable disease
      prevention (NCD), chronic diseases, disaster preparedness, environmental health,
      and others. Training of nursing students in global health while there are
      attending nursing programs needs to be a part of the national and international
      health efforts for disease prevention and health promotion.

PMID- 22459146
TI  - A role for PLCbeta1 in myotonic dystrophies type 1 and 2.
AB  - Phosphoinositide-phospholipase C beta1 (PLCbeta1) plays a crucial role in the
      initiation of the genetic program responsible for muscle differentiation. We
      previously demonstrated that nuclear PLCbeta1 activates the cyclin D3 promoter
      during the differentiation of myoblasts to myotubes, indicating that PLCbeta1 is
      essential for cyclin D3 promoter activation and gene transcription, through c
      jun/AP1. Myotonic dystrophy (DM) is the most prevalent form of muscular dystrophy
      in adults. DM type 1 (DM1) and type 2 (DM2) are dominantly inherited multisystem
      disorders. DM1 is triggered by the pathological expansion of a (CTG)(n) triplet
      repeat in the gene coding for DMPK, the dystrophia myotonica-protein kinase,
      whereas a (CCTG)(n) tetranucleotide repeat expansion in the ZNF9 gene, encoding a
      CCHC-type zinc finger protein, causes DM2. We found that, unlike in normal
      myotubes, the level of expression of PLCbeta1 in DM1 and DM2 cells was already
      elevated in proliferating cells. Treatment with insulin induced a dramatic
      decrease in the amount of PLCbeta1. During differentiation, cyclin D3 and
      myogenin were elevated in normal myotubes, whereas differentiating DM1 and DM2
      cells did not increase these proteins. Forced expression of PLCbeta1 in DM1 and
      DM2 cells increased the expression of differentiation markers, myogenin and
      cyclin D3, and enhanced fusion of DM myoblasts. These results highlight again
      that PLCbeta1 expression is a key player in myoblast differentiation, functioning
      as a positive regulator in the correction of delayed differentiation of skeletal
      muscle in DM human myoblasts.

PMID- 22459147
TI  - A novel stroke therapy of pharmacologically induced hypothermia after focal
      cerebral ischemia in mice.
AB  - Compelling evidence from preclinical and clinical studies has shown that mild to
      moderate hypothermia is neuroprotective against ischemic stroke. Clinical
      applications of hypothermia therapy, however, have been hindered by current
      methods of physical cooling, which is generally inefficient and impractical in
      clinical situations. In this report, we demonstrate the potential of
      pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1
      (NTR1) agonist ABS-201 in a focal ischemic model of adult mice. ABS-201 (1.5-2.5
      mg/kg, i.p.) reduces body and brain temperature by 2-5 degrees C in 15-30 min in
      a dose-dependent manner without causing shivering or altering physiological
      parameters. Infarct volumes at 24 h after stroke are reduced by ~30-40% when PIH
      therapy is initiated either immediately after stroke induction or after 30-60 min
      delay. ABS-201 treatment increases bcl-2 expression, decreases caspase-3
      activation, and TUNEL-positive cells in the peri-infarct region, and suppresses
      autophagic cell death compared to stroke controls. The PIH therapy using ABS-201
      improves recovery of sensorimotor function as tested 21 d after stroke. These
      results suggest that PIH induced by neurotensin analogs represented by ABS-201
      are promising candidates for treatment of ischemic stroke and possibly for other
      ischemic or traumatic injuries.

PMID- 22459148
TI  - MicroRNA-224 is up-regulated in hepatocellular carcinoma through epigenetic
      mechanisms.
AB  - MicroRNA-224 (miR-224) is one of the most commonly up-regulated microRNAs in
      hepatocellular carcinoma (HCC), which affects crucial cellular processes such as
      apoptosis and cell proliferation. In this study, we aim to elucidate the
      molecular mechanism that leads to the overexpression of miR-224 in HCC. We
      examined the transcript expression of miR-224 and neighboring miR-452 and genes
      on chromosome Xq28 in tumor and paired adjacent nontumorous tissues from 100
      patients with HCC and found that miR-224 is coordinately up-regulated with its
      neighboring microRNA (miRNA) and genes. This coordinated up-regulation of miRNAs
      and genes at the Xq28 locus can be mimicked in nontransformed immortalized human
      liver cells by the introduction of histone deacetylase (HDAC) inhibitors, which
      resulted in a corresponding increase in histone H3 acetylation in this region.
      This miR-224-residing locus in Xq28 is reciprocally regulated by HDAC1, HDAC3,
      and histone acetylase protein, E1A binding protein p300 (EP300). Notably, in HCC
      tumors that significantly overexpress microRNA-224, EP300 is also overexpressed
      and displays increased binding to the Xq28 locus. In transformed HCC cells, high
      miR-224 expression can be attenuated through the inhibition of EP300, using
      either siRNA or the specific drug C646. In summary, overexpression of EP300 may
      account, in part, for the up-regulation of miR-224 expression in patients with
      HCC.

PMID- 22459149
TI  - Brain heterotrimeric Galphai2-subunit protein-gated pathways mediate central
      sympathoinhibition to maintain fluid and electrolyte homeostasis during stress.
AB  - Fluid and electrolyte homeostasis is integral to blood pressure regulation.
      However, the central molecular mechanisms regulating the neural control of sodium
      excretion remain unclear. We have demonstrated that brain Galphai(2)-subunit
      protein pathways mediate the natriuretic response to alpha(2)-adrenoreceptor
      activation in vivo. Consequently, we examined the role of brain Galphai(2)
      proteins in the neural mechanisms facilitating fluid and electrolyte homeostasis
      in response to acute [i.v. volume expansion (VE)] or chronic stressful stimuli
      (dietary sodium restriction vs. supplementation) in conscious Sprague-Dawley
      rats. Selective oligodeoxynucleotide (ODN)-mediated down-regulation of brain
      Galphai(2) proteins, but not a scrambled ODN, abolished the renal
      sympathoinhibitory response and attenuated the natriuresis to VE. In scrambled
      ODN-treated rats, chronic changes in dietary sodium intake evoked an endogenous,
      hypothalamic paraventricular nucleus (PVN)-specific, decrease (sodium deficiency)
      or increase (sodium excess) in PVN Galphai(2) proteins; plasma norepinephrine
      levels were inversely related to dietary sodium content. Finally, in rats treated
      with an ODN to prevent high salt-induced up-regulation of brain Galphai(2)
      proteins, animals exhibited sodium retention, global sympathoexcitation, and
      elevated blood pressure. Collectively, these data demonstrate that PVN Galphai(2)
      protein pathways play an endogenous role in maintaining fluid and electrolyte
      balance by controlling the influence the sympathetic nervous system has on the
      renal handling of sodium.

PMID- 22459150
TI  - Lymph node-derived lymphatic endothelial cells express functional costimulatory
      molecules and impair dendritic cell-induced allogenic T-cell proliferation.
AB  - Lymphatic endothelial cells (LECs) interact with different immune cells,
      including T cells within lymph nodes (LNs). However, direct interactions of LECs
      with immune cells have yet to be investigated. In vitro studies were performed to
      characterize primary cultures of human LECs derived from LNs in their capacity of
      interacting with T cells. The results show that LECs express HLA molecules and
      functional costimulatory molecules needed for T-cell activation. A direct binding
      of LECs and T cells was detected in cell cultures connected with a clustering of
      costimulatory molecules on the contact phase. LECs were also able to take up and
      process antigens. However, major histocompatibility complex class II(+) LECs fail
      to induce allogeneic T-cell proliferation. Interestingly, supernatants of IFN
      gamma activated LECs impair proliferation of T cells cocultured with allogeneic
      dendritic cells, suggesting an inhibitory role of LECs. Indoleamine 2,3
      dioxygenase was identified as one inhibitory molecule, which may be responsible
      for the impaired CD4(+) T-cell proliferation. Our observations suggest a
      regulatory function for activated LECs on CD4(+) T cells, which may play a role
      in vivo in the maintenance of the critical balance between tolerance and recall
      responses.

PMID- 22459151
TI  - Circadian expression of H,K-ATPase type 2 contributes to the stability of plasma
      K+ levels.
AB  - Maintenance by the kidney of stable plasma K(+) values is crucial, as plasma K(+)
      controls muscle and nerve activity. Since renal K(+) excretion is regulated by
      the circadian clock, we aimed to identify the ion transporters involved in this
      process. In control mice, the renal mRNA expression of H,K-ATPase type 2 (HKA2)
      is 25% higher during rest compared to the activity period. Conversely, under
      dietary K(+) restriction, HKA2 expression is ~40% higher during the activity
      period. This reversal suggests that HKA2 contributes to the circadian regulation
      of K(+) homeostasis. Compared to their wild-type (WT) littermates, HKA2-null mice
      fed a normal diet have 2-fold higher K(+) renal excretion during rest. Under K(+)
      restriction, their urinary K(+) loss is 40% higher during the activity period.
      This inability to excrete K(+) "on time" is reflected in plasma K(+) values,
      which vary by 12% between activity and rest periods in HKA2-null mice but remain
      stable in WT mice. Analysis of the circadian expression of HKA2 regulators
      suggests that Nrf2, but not progesterone, contributes to its rhythmicity.
      Therefore, HKA2 acts to maintain the circadian rhythm of urinary K(+) excretion
      and preserve stable plasma K(+) values throughout the day.

PMID- 22459152
TI  - The novel chromogranin A-derived serpinin and pyroglutaminated serpinin peptides
      are positive cardiac beta-adrenergic-like inotropes.
AB  - Three forms of serpinin peptides, serpinin (Ala26Leu), pyroglutaminated (pGlu)
      serpinin (pGlu23Leu), and serpinin-Arg-Arg-Gly (Ala29Gly), are derived from
      cleavage at pairs of basic residues in the highly conserved C terminus of
      chromogranin A (CgA). Serpinin induces PN-1 expression in neuroendocrine cells to
      up-regulate granule biogenesis via a cAMP-protein kinase A-Sp1 pathway, while
      pGlu-serpinin inhibits cell death. The aim of this study was to test the
      hypothesis that serpinin peptides are produced in the heart and act as novel beta
      adrenergic-like cardiac modulators. We detected serpinin peptides in the rat
      heart by HPLC and ELISA methods. The peptides included predominantly Ala29Gly and
      pGlu-serpinin and a small amount of serpinin. Using the Langendorff perfused rat
      heart to evaluate the hemodynamic changes, we found that serpinin and pGlu
      serpinin exert dose-dependent positive inotropic and lusitropic effects at 11-165
      nM, within the first 5 min after administration. The pGlu-serpinin-induced
      contractility is more potent than that of serpinin, starting from 1 nM. Using the
      isolated rat papillary muscle preparation to measure contractility in terms of
      tension development and muscle length, we further corroborated the pGlu-serpinin
      induced positive inotropism. Ala29Gly was unable to affect myocardial
      performance. Both pGlu-serpinin and serpinin act through a beta1-adrenergic
      receptor/adenylate cyclase/cAMP/PKA pathway, indicating that, contrary to the
      beta-blocking profile of the other CgA-derived cardiosuppressive peptides,
      vasostatin-1 and catestatin, these two C-terminal peptides act as beta-adrenergic
      like agonists. In cardiac tissue extracts, pGlu-serpinin increased intracellular
      cAMP levels and phosphorylation of phospholamban (PLN)Ser16, ERK1/2, and GSK
      3beta. Serpinin and pGlu-serpinin peptides emerge as novel beta-adrenergic
      inotropic and lusitropic modulators, suggesting that CgA and the other derived
      cardioactive peptides can play a key role in how the myocardium orchestrates its
      complex response to sympathochromaffin stimulation.

PMID- 22459153
TI  - The Psen1-L166P-knock-in mutation leads to amyloid deposition in human wild-type
      amyloid precursor protein YAC transgenic mice.
AB  - Genetically engineered mice have been generated to model cerebral beta
      amyloidosis, one of the hallmarks of Alzheimer disease (AD) pathology, based on
      the overexpression of a mutated cDNA of the amyloid-beta precursor protein
      (AbetaPP) or by knock-in of the murine Abetapp gene alone or with presenilin1
      mutations. Here we describe the generation and initial characterization of a new
      mouse line based on the presence of 2 copies of the human genomic region encoding
      the wild-type AbetaPP and the L166P presenilin 1 mutation. At ~6 mo of age,
      double-mutant mice develop amyloid pathology, with signs of neuritic dystrophy,
      intracellular Abeta accumulation, and glial inflammation, an increase in AbetaPP
      C-terminal fragments, and an 8 times increase in Abeta42 levels with a 40%
      decrease in Abeta40 levels, leading to a significant increase (14 times) of
      Abeta42/Abeta40 ratios, with minimal effects on presenilin or the Notch1 pathway
      in the brain. We conclude that in mice, neither mutations in AbetaPP nor
      overexpression of an AbetaPP isoform are a prerequisite for Abeta pathology. This
      model will allow the study of AD pathogenesis and testing of therapeutic
      strategies in a more relevant environment without experimental artifacts due to
      the overexpression of a single-mutant AbetaPP isoform using exogenous promoters.

PMID- 22459154
TI  - Development of a long-term ovine model of cutaneous burn and smoke inhalation
      injury and the effects of early excision and skin autografting.
AB  - Smoke inhalation injury frequently increases the risk of pneumonia and mortality
      in burn patients. The pathophysiology of acute lung injury secondary to burn and
      smoke inhalation is well studied, but long-term pulmonary function, especially
      the process of lung tissue healing following burn and smoke inhalation, has not
      been fully investigated. By contrast, early burn excision has become the standard
      of care in the management of major burn injury. While many clinical studies and
      small-animal experiments support the concept of early burn wound excision, and
      show improved survival and infectious outcomes, we have developed a new chronic
      ovine model of burn and smoke inhalation injury with early excision and skin
      grafting that can be used to investigate lung pathophysiology over a period of 3
      weeks. MATERIALS AND METHODS: Eighteen female sheep were surgically prepared for
      this study under isoflurane anesthesia. The animals were divided into three
      groups: an Early Excision group (20% TBSA, third-degree cutaneous burn and 36
      breaths of cotton smoke followed by early excision and skin autografting at 24h
      after injury, n=6), a Control group (20% TBSA, third-degree cutaneous burn and 36
      breaths of cotton smoke without early excision, n=6) and a Sham group (no injury,
      no early excision, n=6). After induced injury, all sheep were placed on a
      ventilator and fluid-resuscitated with Lactated Ringers solution (4 mL/% TBS/kg).
      At 24h post-injury, early excision was carried out to fascia, and skin grafting
      with meshed autografts (20/1000 in., 1:4 ratio) was performed under isoflurane
      anesthesia. At 48 h post-injury, weaning from ventilator was begun if
      PaO(2)/FiO(2) was above 250 and sheep were monitored for 3 weeks. RESULTS: At 96
      h post-injury, all animals were weaned from ventilator. There are no significant
      differences in PaO(2)/FiO(2) between Early Excision and Control groups at any
      points. All animals were survived for 3 weeks without infectious complication in
      Early Excision and Sham groups, whereas two out of six animals in the Control
      group had abscess in lung. The percentage of the wound healed surviving area
      (mean +/- SD) was 74.7 +/- 7.8% on 17 days post-surgery in the Early Excision
      group. Lung wet-to-dry weight ratio (mean +/- SD) was significantly increased in
      the Early Excision group vs. Sham group (p<0.05). The calculated net fluid
      balance significantly increased in the early excision compared to those seen in
      the Sham and Control groups. Plasma protein, oncotic pressure, hematocrit of %
      baseline, hemoglobin of % baseline, white blood cell and neutrophil were
      significantly decreased in the Early Excision group vs. Control group.
      CONCLUSIONS: The early excision model closely resembles practice in a clinical
      setting and allows long-term observations of pulmonary function following burn
      and smoke inhalation injury. Further studies are warranted to assess lung tissue
      scarring and measuring collagen deposition, lung compliance and diffusion
      capacity.

PMID- 22459155
TI  - A burn center paradigm to fulfill deferred consent public disclosure and
      community consultation requirements for emergency care research.
AB  - INTRODUCTION: To fulfill Food and Drug Administration and Department of Health
      and Human Services emergency care research informed consent requirements, our
      burn center planned and executed a deferred consent strategy gaining
      Institutional Review Board (IRB) approval to proceed with the clinical study.
      These federal regulations dictate public disclosure and community consultation
      unique to acute care research. OBJECTIVE: Our regional burn center developed and
      implemented a deferred consent public notification and community consultation
      paradigm appropriate for a burn study. METHODS: Published accounts of deferred
      consent strategies focus on acute care resuscitation practices. We adapted those
      strategies to design and conduct a comprehensive public notification/community
      consultation plan to satisfy deferred consent requirements for burn center
      research. RESULTS: To implement a robust media campaign we engaged the hospital's
      public relations department, distributed media materials, recruited hospital
      staff for speaking engagements, enlisted community volunteers, and developed
      initiatives to inform "hard-to-reach" populations. The hospital's IRB determined
      we fulfilled our obligation to notify the defined community. CONCLUSION: Our
      communication strategy should provide a paradigm other burn centers may
      appropriate and adapt when planning and executing a deferred consent initiative.

PMID- 22459156
TI  - Continuous intravenous administration of vancomycin in medical intensive care
      unit patients.
AB  - PURPOSE: The aim of this study was to evaluate continuous vancomycin infusion
      (contV) in intensive care unit patients. MATERIALS AND METHODS: A retrospective
      study in 164 patients treated with contV was conducted. They were compared with
      75 patients treated with intermittent vancomycin infusion. RESULTS: The median
      duration of vancomycin therapy in the contV group was 6 (5%-95% percentile range,
      2-21) days. The median daily vancomycin dose in the contV group was 960 (526
      1723) mg, resulting in a median serum vancomycin plateau concentration of 19.8
      (9.8-29.4) mg/L (target: 15-25 mg/L). The contV administration regime was
      sufficient regarding achievement of the target serum vancomycin concentration.
      However, in the contV group, serum vancomycin levels were frequently in a
      subtherapeutic range on treatment days 1 (44%), 2 (29%), and 3 (23%). In the
      contV group, serum vancomycin concentration determinations per treatment day were
      performed significantly less often compared with the intermittent vancomycin
      infusion group (0.38 [0.15-0.75] vs 0.43 [0.22-1.00], P = .041). CONCLUSIONS: In
      medical intensive care unit patients, contV is sufficient to achieve target serum
      vancomycin concentrations. Because contV frequently resulted in subtherapeutic
      drug levels on the first days of therapy, a higher loading or starting dose might
      be necessary.

PMID- 22459157
TI  - Antibiotic resistance patterns in medical and surgical patients in a combined
      medical-surgical intensive care unit.
AB  - PURPOSE: Studies have found different rates of antimicrobial resistance among
      patients in medical and surgical intensive care units (ICUs). We studied whether
      these differences were a function of geography or differences in the patient
      populations, by comparing resistance rates among bacteria isolated from a
      combined medical/surgical ICU. MATERIALS AND METHODS: We retrospectively
      evaluated the results of bacterial cultures of each patient admitted to the ICU
      between February 2005 and September 2006. Data collection included patient
      demographics and culture and sensitivity results. Intensive care unit populations
      were compared using the Fisher exact test and the Student t test. RESULTS: One
      hundred seventy-one medical and 94 surgical patients with positive cultures were
      studied. Organisms were grouped into 4 classes: Staphylococcus aureus, nonlactose
      fermenting gram-negative bacilli, Enterococcus species, and gram-negative enteric
      bacteria. In the 4 classes, no significant difference in antibiotic resistance
      was found between medical and surgical patients. CONCLUSION: Reported differences
      in resistance patterns among bacteria cultured from medical and surgical patients
      may be due to geographic separation of the ICUs as opposed to differences in the
      patient characteristics. This study suggests that ICU-specific antibiograms
      remain a useful tool to guide the choice of antimicrobial therapy, even in
      medical/surgical ICUs.

PMID- 22459158
TI  - Mechanical ventilation in the emergency department for 24 hours or longer is
      associated with delayed weaning.
AB  - PURPOSE: We examined various aspects of critical care to identify factors in the
      emergency department (ED) that affected the overall duration of mechanical
      ventilation (MV). We specifically focused on whether 24 hours of ED MV affected
      the weaning success and the duration of MV. MATERIALS AND METHODS: Mechanical
      ventilation cases that started in the ED because of purely respiratory problems
      were enrolled in the retrospective cohort. We recorded demographic data, duration
      of MV in ED, various severity scores, previously known factors of prolonged MV,
      and achievement of ventilator weaning. All the significant factors in univariate
      survival analyses were included in a multivariate analysis. RESULTS: The
      estimated median of the entire duration of MV was longer in patients who received
      24 hours or more of MV in ED compared with that of patients who received MV for
      less than 24 hours (33.0 vs 15.4 days, P = .003). Mechanical ventilation for
      longer than 24 hours in the ED remained a significant factor that prolonged the
      entire MV duration in the multivariate analysis (hazard ratio, 0.577; P = .019).
      Hypoalbuminemia and abbreviated mortality in ED sepsis (MEDS) score were also
      independently correlated (P <= .001 for both). CONCLUSIONS: Mechanical
      ventilation in the ED for 24 hours or longer is associated with delayed
      ventilator weaning.

PMID- 22459159
TI  - The effect of body position changes on stroke volume variation in 66 mechanically
      ventilated patients with sepsis.
AB  - PURPOSE: The aim of the study was to investigate the effect of body position
      changes on the stroke volume (SI) variation (SVV) in ventilated patients with
      sepsis. METHODS: Sixty patients with sepsis were studied during mechanical
      ventilation. All patients were randomly placed in the supine, 30 degrees  head
      up, 30 degrees  left or right recumbent, or prone position. In addition to
      standard hemodynamic monitoring, SVV, central venous pressure, cardiac index
      (CI), SV index (SVI), global end-diastolic volume index (GEDVI), and global
      ejection fraction (GEF) were recorded at each position after stabilization.
      RESULTS: Stroke volume variation had strong negative correlation with CI, SVI,
      GEF, and GEDVI (P < .0001). After the change to the 30 degrees  head-up or the
      prone position, SVV increased significantly, whereas CI, SVI, GEF, and GEDVI
      decreased dramatically. Stroke volume variation in the supine position did not
      correlate with 30 degrees  head-up- or prone-induced changes in CI (P < .05). All
      variables did not differ between 30 degrees  left or right recumbent and supine
      positions. CONCLUSIONS: Body position changes may affect the correlation of SVV
      with hemodynamic variables. The 30 degrees  head-up and prone positions increased
      SVV because of the associated decreased SV. The 30 degrees  left or right
      recumbent position does not affect SVV and SV.

PMID- 22459160
TI  - Comparison of 3 modes of automated weaning from mechanical ventilation: a bench
      study.
AB  - PURPOSE: Automated weaning modes are available in some mechanical ventilators,
      but no studies compared them hitherto. We compared the performance of 3 automated
      modes under standard and challenging situations. METHODS: We used a lung
      simulator to compare 3 automated modes, adaptive support ventilation (ASV),
      mandatory rate ventilation (MRV), and Smartcare, in 6 situations, weaning
      success, weaning failure, weaning success with extreme anxiety, weaning success
      with Cheyne-Stokes, weaning success with irregular breathing, and weaning failure
      with ineffective efforts. RESULTS: The 3 modes correctly recognized the
      situations of weaning success and failure, even when anxiety or irregular
      breathing were present but incorrectly recognized weaning success with Cheyne
      Stokes. MRV incorrectly recognized weaning failure with ineffective efforts. Time
      to pressure support (PS) stabilization was shorter for ASV (1-2 minutes for all
      situations) and MRV (1-7 minutes) than for Smartcare (8-78 minutes). ASV had
      higher rates of PS oscillations per 5 minutes (4-15), compared with Smartcare (0
      1) and MRV (0-12), except when extreme anxiety was present. CONCLUSIONS:
      Smartcare, ASV, and MRV were equally able to recognize weaning success and
      failure, despite the presence of anxiety or irregular breathing but performed
      incorrectly in the presence of Cheyne-Stokes. PS behavior over the time differs
      among modes, with ASV showing larger and more frequent PS oscillations over the
      time. Clinical studies are needed to confirm our results.

PMID- 22459162
TI  - Oral cavity discrimination of vapor-phase long-chain 18-carbon fatty acids.
AB  - Linoleic, oleic, and stearic fatty acids, presented vapor-phase retronasally,
      were discriminable from blanks and each other, but the same concentrations, oral
      cavity-only (OCO), were not discriminable from blanks. It remained possible that
      higher concentrations might be discriminable OCO. To evaluate this, participants
      attempted to discriminate undiluted linoleic, oleic, or stearic acids, vapor
      phase OCO, from blanks. For each fatty acid, participants received 5 stimulus
      delivery containers (SDCs) in 2 trials; 4 SDC held blanks, the fifth, a fatty
      acid. As a "positive control" in 2 trials, participants received vapor-phase OCO
      peppermint extract and blanks. For all trials, the task was to select the 1
      different SDC. It was found that the 1 different SDC was selected in 24% of
      stearic, 32% of linoleic, 47% of oleic acid, and in 92% of peppermint trials;
      discriminations (the 1 different SDC selected in both trials) occurred in 0%,
      16%, 26%, and 84% of pairs, respectively. Correct selections for oleic acid
      differed from chance, P = 0.0004, but not for linoleic acid, P = 0.125, or
      stearic acid, P = 0.345, Bonferroni corrected. Vapor-phase oleic acid can be an
      oral cavity trigeminal stimulus, linoleic acid might be (uncorrected P = 0.0384),
      but vapor-phase stearic acid cannot be.

PMID- 22459161
TI  - Are you or aren't you? Challenges associated with physiologically identifying
      dopamine neurons.
AB  - The dopamine system is involved in motivation, reward and learning, and
      dysfunction in this system has been implicated in several disorders, including
      Parkinson's disease (PD) and schizophrenia. Key progress in our understanding of
      its functions has come from extracellular in vivo electrophysiological recordings
      from midbrain dopamine neurons. Numerous studies have used a defined set of
      criteria to identify dopamine neurons electrophysiologically. However, a few
      recent studies have suggested that a minority population of non-dopamine neurons
      may not be readily distinguishable from dopamine neurons, raising questions as to
      the reliability of past findings. We provide an overview of the key findings
      related to this controversy and assess the criteria used for the
      electrophysiological identification of dopamine neurons in the substantia nigra
      pars compacta (SNC) and ventral tegmental area (VTA).

PMID- 22459163
TI  - Multimodal sensory integration during sequential eating--linking chewing
      activity, aroma release, and aroma perception over time.
AB  - The respective effects of chewing activity, aroma release from a gelled candy,
      and aroma perception were investigated. Specifically, the study aimed at 1)
      comparing an imposed chewing and swallowing pattern (IP) and free protocol (FP)
      on panelists for in vivo measurements, 2) investigating carryover effects in
      sequential eating, and 3) studying the link between instrumental data and their
      perception counterpart. Chewing activity, in-nose aroma concentration, and aroma
      perception over time were measured by electromyography, proton transfer reaction
      mass spectrometry, and time intensity, respectively. Model gel candies were
      flavored at 2 intensity levels (low-L and high-H). The panelists evaluated 3
      sequences (H then H, H then L, and L then H) in duplicates with both IP and FP.
      They scored aroma intensity over time while their in-nose aroma concentrations
      and their chewing activity were measured. Overall, only limited advantages were
      found in imposing a chewing and swallowing pattern for instrumental and sensory
      data. In addition, the study highlighted the role of brain integration on
      perceived intensity and dynamics of perception, in the framework of sequential
      eating without rinsing. Because of the presence of adaptation phenomena, contrast
      effect, and potential taste and texture cross-modal interaction with aroma
      perception, it was concluded that dynamic in-nose concentration data provide only
      one part of the perception picture and therefore cannot be used alone in
      prediction models.

PMID- 22459164
TI  - Spatial organization of antennal olfactory sensory neurons in the female
      Spodoptera littoralis moth: differences in sensitivity and temporal
      characteristics.
AB  - Single-cell recordings from olfactory sensory neurons (OSNs), housed in sensilla
      located at the base and at the tip of the antenna, showed selective responses to
      plant odors and female sex pheromone in this polyphagous moth. A spatial
      variation existed in sensitivity: OSNs present on the more proximal segment (P)
      were more sensitive than those on the more distal segment (D). OSNs of the 2
      locations also differed in temporal characteristics: OSNs on P had shorter
      latency and displayed more phasic responses, whereas those on D had more tonic
      responses, especially at low stimulus concentrations. The 196 OSNs responding to
      our 35 monomolecular stimuli in the screening were housed in 32 functional
      sensillum types: 27 in basiconic, 3 in long-trichoid, 2 in coeloconic, and 3 in
      auricillic sensilla. The OSNs in basiconic, coeloconic, and auricillic sensilla
      responded to plant-associated odorants, whereas OSNs in long-trichoid sensilla
      responded to female-produced sex pheromone components. Short-trichoid sensilla
      showed spontaneous activity, but no responses to any odorant tested. OSN
      specificity to plant stimuli ranged from highly specific to broadly tuned, but it
      did not differ clearly from females in more specialized moths. OSN response
      diversity is discussed in terms of olfactory coding, behavior, and ecological
      specialization.

PMID- 22459165
TI  - Cluster analysis of rat olfactory bulb responses to diverse odorants.
AB  - In an effort to deepen our understanding of mammalian olfactory coding, we have
      used an objective method to analyze a large set of odorant-evoked activity maps
      collected systematically across the rat olfactory bulb to determine whether such
      an approach could identify specific glomerular regions that are activated by
      related odorants. To that end, we combined fuzzy c-means clustering methods with
      a novel validity approach based on cluster stability to evaluate the significance
      of the fuzzy partitions on a data set of glomerular layer responses to a large
      diverse group of odorants. Our results confirm the existence of glomerular
      response clusters to similar odorants. They further indicate a partial
      hierarchical chemotopic organization wherein larger glomerular regions can be
      subdivided into smaller areas that are rather specific in their responses to
      particular functional groups of odorants. These clusters bear many similarities
      to, as well as some differences from, response domains previously proposed for
      the glomerular layer of the bulb. These data also provide additional support for
      the concept of an identity code in the mammalian olfactory system.

PMID- 22459166
TI  - The interaction of the ubiquitin 50-59 fragment with copper(II) ions.
AB  - In the present study, the coordination abilities of ubiquitin 50-59 fragment and
      its analog containing betaAsp residue are discussed. The analysis is provided
      based on the results of potentiometric and spectroscopic measurements supported
      by quantum-chemical calculations. Interesting differences in the coordination of
      the metal cation by modified and unmodified peptides are reported. Moreover, in
      order to further characterize experimentally observed species, we performed
      quantum-chemical calculations for structures mimicking ubiquitin 50-59 fragment
      as a step toward a better understanding of structural and energetical aspects
      related to the coordination abilities of ubiquitin.

PMID- 22459167
TI  - Phosphate inhibits in vitro Fe3+ loading into transferrin by forming a soluble
      Fe(III)-phosphate complex: a potential non-transferrin bound iron species.
AB  - In chronic kidney diseases, NTBI can occur even when total iron levels in serum
      are low and transferrin is not saturated. We postulated that elevated serum
      phosphate concentrations, present in CKD patients, might disrupt Fe(3+) loading
      into apo-transferrin by forming Fe(III)-phosphate species. We report that
      phosphate competes with apo-transferrin for Fe(3+) by forming a soluble Fe(III)
      phosphate complex. Once formed, the Fe(III)-phosphate complex is not a substrate
      for donating Fe(3+) to apo-transferrin. Phosphate (1-10mM) does not chelate
      Fe(III) from diferric transferrin under the conditions examined. Complexed forms
      of Fe(3+), such as iron nitrilotriacetic acid (Fe(3+)-NTA), and Fe(III)-citrate
      are not susceptible to this phosphate complexation reaction and efficiently
      deliver Fe(3+) to apo-transferrin in the presence of phosphate. This reaction
      suggests that citrate might play an important role in protecting against Fe(III),
      phosphate interactions in vivo. In contrast to the reactions of Fe(3+) and
      phosphate, the addition of Fe(2+) to a solution of apo-transferrin and phosphate
      lead to rapid oxidation and deposition of Fe(3+) into apo-transferrin. These in
      vitro data suggest that, in principle, elevated phosphate concentrations can
      influence the ability of apo-transferrin to bind iron, depending on the oxidation
      state of the iron.

PMID- 22459169
TI  - Sulfonated Ni(II)porphyrin improves the detection of Z-DNA in condensed and non
      condensed BZB DNA sequences.
AB  - We report a very selective and sensitive spectroscopic detection of Z-DNA
      embedded in B-DNA in condensed as well as non-condensed DNA using anionic Ni(II)
      meso-tetrakis(4-sulphonatophenyl)porphyrin, NiTPPS. A combination of micromolar
      concentrations of Ni(II) and spermine(4+) allowed us to prepare left-handed Z-DNA
      in short oligonucleotides without DNA condensation. A strong induced circular
      dichroism (ICD) signal was observed in the visible absorption region when NiTPPS
      was added to BZ DNA (Z-DNA fragment located at the end of a B-DNA tract with one
      B/Z DNA junction) and BZB DNA (Z-DNA sequence embedded in B-DNA having two B/Z
      DNA junctions). Almost no ICD signal was detected when NiTPPS was added to B-DNA.
      NiTPPS showed different binding modes with condensed and non-condensed Z-DNAs and
      allowed the distinction between condensed Z-DNA (positive bisignate CD couplet)
      and non-condensed Z-DNA (negative bisignate CD couplet).

PMID- 22459168
TI  - The CXXC motifs in the metal binding domains are required for ATP7B to mediate
      resistance to cisplatin.
AB  - The copper (Cu) exporter ATP7B mediates resistance to cisplatin (cDDP) but
      details of the mechanism are unknown. We explored the role of the CXXC motifs in
      the metal binding domains (MBDs) of ATP7B by investigating binding of cDDP to the
      sixth metal binding domain (MBD6) or a variant in which the CXXC motif was
      converted to SXXS. Platinum measurement showed that cDDP bound to wild type MBD6
      but not to the SXXS variant. Wild type ATP7B rendered ovarian 2008 cells
      resistant to cDDP. In 2008 and in HEK293T cells, wild type ATP7B trafficked from
      TGN to peripheral locations in response to Cu or cDDP. A variant in which the
      CXXC motifs in all 6 MBDs were converted to SXXS localized correctly to the TGN
      but failed to traffic when exposed to either Cu or cDDP. Deletion of either the
      first 5 MBDs or all 6 MBDs resulted in failure to localize to the TGN. Neither
      the SXXS variant nor the deletion variant was able to mediate resistance to cDDP.
      We conclude that cDDP binds to the CXXC motifs of ATP7B and that this interaction
      is essential to the trafficking of ATP7B and to its ability to mediate resistance
      to cDDP.

PMID- 22459170
TI  - In vitro study of percutaneous absorption of aluminum from antiperspirants
      through human skin in the FranzTM diffusion cell.
AB  - Aluminum salts such as aluminum chlorohydrate (ACH) are known for use as an
      active antiperspirant agent that blocks the secretion of sweat. A local case
      report of hyperaluminemia in a woman using an aluminum-containing antiperspirant
      for 4 years raises the problem of transdermal absorption of aluminum (Al). Only a
      very limited number of studies have shown that the skin is an effective barrier
      to transdermal uptake of Al. In accordance with our analytical procedure, the aim
      of this study with an in vitro FranzTM diffusion cell was to measure aluminum
      uptake from three cosmetic formulations of antiperspirant: the base for an
      "aerosol" (38.5% of ACH), a "roll-on" emulsion (14.5% ACH), and a "stick"
      (21.2%), by samples of intact and stripped human skin (5 donors). The Al assays
      were performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry
      (ZEAAS). Following contacts lasting 6, 12 and 24h, the Al assays showed only
      insignificant transdermal absorption of Al (<=0.07% of the quantity of Al
      deposited) and particularly low cutaneous quantities that varied according to the
      formulations (1.8 MUg/cm2 for "aerosol base" and "stick" - 0.5 MUg/cm2 for the
      "roll-on"). On stripped skin, for which only the "stick" formulation was tested,
      the measured uptake was significantly higher (11.50 MUg/cm2 versus 1.81 MUg/cm2
      for normal skin). These results offer reassurance as regards to the use of
      antiperspirants for topical application of ACH-containing cosmetic formulations
      on healthy skin over a limited time span (24h). On the other hand, high
      transdermal Al uptake on stripped skin should compel antiperspirant manufacturers
      to proceed with the utmost caution.

PMID- 22459171
TI  - 1H, 13C MAS NMR and DFT GIAO study of quercetin and its complex with Al(III) in
      solid state.
AB  - Quercetin (Q) as a pentahydroxy flavonoid, has three possible chelating sites
      competing in complexation processes. (1)H and (13)C MAS NMR spectra were recorded
      for solid quercetin and its Al(III) complex (AlQ). (1)H MAS spectrum of quercetin
      shows a broad resonance at ca. 12 ppm that confirms the existence of
      intramolecular C5-OH ... O=C4 hydrogen bond. Such a signal is absent in the
      spectrum of AlQ, which is in accordance with other spectroscopic data and the
      suggested model for the solid-state structure of the complex. DFT GIAO
      calculations were used to verify the experimental (13)C CPMAS NMR data and to
      suggest the best model structure for the complex AlQ. The calculated shielding
      constants for different conformers of isolated quercetin molecules, quercetin
      trimer as taken from the X-ray data, and different model structures for possible
      Al(III) complexes were compared with the (13)C CPMAS NMR experimental values. The
      results demonstrate the importance of intermolecular interactions when dealing
      with structures in solid state and the successful application of the combined DFT
      GIAO and (13)C CPMAS NMR approach. All data confirm that the chelating site of Q
      in the solid complex AlQ involves the deprotonated C5-OH and the C4=O groups at
      ring C, in contrast to the available studies performed in solution.

PMID- 22459172
TI  - Inhibition of beta-carbonic anhydrases from the bacterial pathogen Brucella suis
      with inorganic anions.
AB  - The bacterial pathogen Brucella suis encodes two carbonic anhydrases (CAs, EC
      4.2.1.1) belonging to the beta-class, bsCA1 and bsCA2, which are crucial for its
      life cycle. Sulfonamides, strong inhibitors of these enzymes, were shown to block
      the growth of the pathogen in vitro. Here we report the inhibition of these two
      CAs by inorganic and complex anions and other molecules interacting with zinc
      proteins, such as sulfamide, sulfamic acid, and phenylboronic/arsonic acids. The
      enzyme bsCA1 was inhibited in the low micromolar range by sulfamide, sulfamic
      acid, phenylboronic/arsonic acid, and in the submillimolar range by
      diethyldithiocarbamate. Isoform bsCA2 generally showed a stronger inhibition with
      most of these anions, with several low micromolar and many submillimolar
      inhibitors detected. Micromolar inhibition against bsCA2 was observed for
      sulfamide and sulfamic acid, whereas diethyldithiocarbamate, perruthenate,
      pyrovanadate, tellurate and phenylarsonic acid showed inhibition constants in the
      range of 0.29-1.52mM. These inhibitors may be used as leads for developing anti
      Brucella agents with a diverse mechanism of action compared to clinically used
      antibiotics.

PMID- 22459173
TI  - Binding of quinidine radically increases the stability and decreases the
      flexibility of the cytochrome P450 2D6 active site.
AB  - Human cytochrome P450 2D6 (CYP2D6) is an enzyme of the CYP superfamily
      responsible for biotransformation of about 20% of drugs of known metabolism
      containing a basic nitrogen and a planar aromatic ring. Here, we present a
      combined experimental and computational study on the compressibility and
      flexibility of unliganded and quinidine-bound CYP2D6. Experimentally, high
      pressure induced Soret band shifts of the enzyme were measured by UV/VIS
      spectroscopy, while 100 ns all atomic molecular dynamics (MD) simulations in
      explicit water were used in the computational analysis. We identified sharp
      differences between ligand-free and quinidine-bound CYP2D6 forms in
      compressibility, flexibility parameters and active site solvation. While the
      unliganded CYP2D6 is compressible, quinidine binding significantly rigidifies the
      CYP2D6 active site. In addition, MD simulations show that quinidine binding
      results in pronounced reductions in active site flexibility and solvation.

PMID- 22459174
TI  - Synthesis, cytotoxicity and structure-activity relationships between ester and
      amide functionalities in novel acridine-based platinum(II) complexes.
AB  - In order to improve the pharmacological profile of the anticancer drug cisplatin,
      several new acridine-based tethered (ethane-1,2-diamine)platinum(II) complexes
      connected by a polymethylene chain were synthetized. Activity-structure
      relationship between amide or ester functionalities was explored by changing
      acridine-9-carboxamide into acridine-9-carboxylate chromophore. The in vitro
      cytotoxicity of these new complexes was assessed in human colic HCT 116, SW480
      and HT-29 cancer cell lines. Series of complexes bearing the acridine-9
      carboxylate chromophore displayed higher cytotoxic effect than acridine-9
      carboxamide complexes, with gradual effect according to the size of the
      polymethylene linker.

PMID- 22459175
TI  - PI3-K/Akt/JNK/NF-kappaB is essential for MMP-9 expression and outgrowth in human
      limbal epithelial cells on intact amniotic membrane.
AB  - Matrix metalloproteinase-9 (MMP-9) plays an important role in the outgrowth of
      expanded human limbal epithelial cells on intact amniotic membranes (AM). The
      mechanisms of MMP-9 expression and cell outgrowth remain unknown. Here, we
      demonstrated that MMP-9 is preferentially expressed at the leading edge of limbal
      epithelial outgrowth. Treatment with the inhibitors of PI3-K (LY294002), Akt (SH
      5), MEK1/2 (U0126), and JNK1/2 (SP600125) attenuated the outgrowth area,
      indicating that PI3-K/Akt, p42/p44 MAPK, and JNK1/2 are involved in the outgrowth
      of intact AM-expanded limbal epithelial cells. However, MMP-9 expression at both
      transcriptional and translational levels was attenuated by treatment with
      SP600125, LY294002, or SH-5, not by U0126 and SB202190, suggesting that JNK1/2
      and PI3-K/Akt participate in MMP-9 expression. Moreover, NF-kappaB
      phosphorylation and nuclear translocation was especially noted at the leading
      edge, which was attenuated by treatment with SP600125 or LY294002. Helenalin, a
      selective NF-kappaB inhibitor, reduced both the limbal epithelial outgrowth and
      MMP-9 expression. Finally, the data reveal that PI3-K/Akt is an upstream
      component of the JNK1/2 pathway in MMP-9 expression. Thus, both MAPKs and PI3
      K/Akt are required for limbal epithelial outgrowth on intact AM, only the PI3
      K/Akt/JNK is essential for MMP-9 expression mediated through activation of
      transcriptional factor NF-kappaB in this model.

PMID- 22459176
TI  - Motor branch of extensor carpi radialis longus: anatomic localization.
AB  - OBJECTIVE: To identify extensor carpi radialis longus (ECRL) motor nerve
      coordinates in relation to anatomic surface landmarks. DESIGN: Descriptive study.
      SETTING: Anatomy institute of a school of medicine in Paris, France. CADAVERS:
      Fresh adult cadaver upper limbs (N=20). INTERVENTION: Anatomic dissection of
      upper limbs. MAIN OUTCOME MEASURES: Three measurements (mm) were taken of the
      position of the ECRL motor branch: the distance between the lateral epicondyle
      and the emergence of the ECRL branch along the forearm axis, the branch depth,
      and the ratio between the distance corresponding to the nerve depth and the
      intercondylar distance. RESULTS: The radial nerves of 4 men and 6 women (age
      range 59-80 y) were identified between the brachioradialis and the ECRL and
      traced proximally to the lateral epicondyle. The injection point was between the
      lateral epicondyle posteriorly and the wrist extensor group anteriorly. Direction
      was perpendicular to the axis of the forearm. Mean depth was 35.6 mm (minimal
      value: 24.0; maximal value: 58.0; SD=9 mm). Ratio between nerve depth and
      intercondylar distance was .46 (.37; .53+/-.05). CONCLUSIONS: The ECRL motor
      nerve branch is easy to reach using specified landmarks. Selective motor nerve
      block of the ECRL branch should be considered in the clinical assessment to test
      the capacity of the extensor carpi radialis brevis to extend the wrist alone and
      to assess the command and overactivity of antagonists before surgery.

PMID- 22459177
TI  - Patient Protection and Affordable Care Act: potential effects on physical
      medicine and rehabilitation.
AB  - The objective was to review pertinent areas of the Patient Protection and
      Affordable Care Act (PPACA) to determine the PPACA's impact on physical medicine
      and rehabilitation (PM&R). The law, and related newspaper and magazine articles,
      was reviewed. The ways in which provisions in the PPACA are being implemented by
      the Centers for Medicare and Medicaid Services and other government organizations
      were investigated. Additionally, recent court rulings on the PPACA were analyzed
      to assess the law's chances of successful implementation. The PPACA contains a
      variety of reforms that, if implemented, will significantly impact the field of
      PM&R. Many PPACA reforms change how rehabilitative care is delivered by
      integrating different levels of care and creating uniform quality metrics to
      assess quality and efficiency. These quality metrics will ultimately be tied to
      new, performance-based payment systems. While the law contains ambitious
      initiatives that may, if unsuccessful or incorrectly implemented, negatively
      impact PM&R, it also has the potential to greatly improve the quality and
      efficiency of rehabilitative care. A proactive approach to the changes the PPACA
      will bring about is essential for the health of the field.

PMID- 22459178
TI  - Immediate procedural outcomes in 35 consecutive pipeline embolization cases: a
      single-center, single-user experience.
AB  - BACKGROUND AND OBJECTIVE: Flow diverters are an exciting new class of
      endovascular devices that treat aneurysms by curative reconstruction of the
      parent artery. The Pipeline embolization device (PED) is the first FDA-approved
      intracranial flow diverting device available in the USA. This paper presents
      periprocedural results with the device in a series of 35 consecutive cases.
      METHODS: All patients who underwent PED treatment of an intracranial aneurysm at
      our institution following FDA approval of the device in April 2011 were included
      in the series. Patient demographics, aneurysm characteristics, procedural details
      and technical and clinical outcomes were analyzed. RESULTS: Thirty-four patients
      (age range 23-78 years, mean 56.4 years) with 41 unruptured aneurysms (37
      anterior circulation, four posterior circulation, mean size 11.4 mm, 20/21 large
      or giant) were treated with the PED in 35 cases (one patient had bilateral
      aneurysms treated on 2 separate occasions). Thirty-four of 35 cases (97%) were
      successfully completed. A total of 64 PEDs were implanted, with a mean number of
      1.2 PEDs implanted per anterior circulation cases and 6.5 per posterior
      circulation cases. A single PED was implanted in 73% of cases. Immediate flow
      disruption occurred in 97% of the cases. The overall rate of major stroke or
      mortality was 3% (1/35 patients). Minor stroke, cranial nerve palsy, transient
      neurological deficit and groin complication occurred in one patient each (3%
      each, 12% total). CONCLUSION: Treatment of cerebral aneurysms with the PED
      carries an acceptable risk profile when a rigorous and uniform technique is used.
      Although the long-term results will need to be analyzed, the immediate procedural
      outcomes in the study series using this technique appear quite promising.

PMID- 22459179
TI  - PI3K/Akt pathway activation was involved in acute ethanol-induced fatty liver in
      mice.
AB  - Accumulating evidences support the important roles of sterol regulatory element
      binding protein-1 (SREBP-1) activation in ethanol-induced fatty liver, but the
      underlying mechanisms for its activation are not fully understood. Recent studies
      have demonstrated that phosphatidylinositol 3 kinase (PI3K)/Akt pathway
      activation could enhance SREBP-1 activity. The current study was designed to
      investigate the potential roles of PI3K/Akt pathway in acute ethanol-induced
      fatty liver in mice. In the first experiment, mice were treated with ethanol (2.5
      or 5 g/kg bw) or isocaloric/isovolumetric maltose-dextrin solution, and
      sacrificed at several time points after ethanol exposure. As expected, ethanol
      dose-dependently increased the hepatic triglyceride (TG) levels and the protein
      levels of the mature form of SREBP-1 (n-SREBP-1). The phosphorylation of Akt and
      glycogen synthase kinase-3beta (GSK-3beta) was significantly increased in mice
      treated with ethanol (5 g/kg bw), while the protein levels of PI3K-p85 were
      significantly reduced. To confirm the roles of PI3K/Akt pathway, mice were then
      pretreated with wortmannin (0.7 or 1.4 mg/kg bw), a specific PI3K/Akt pathway
      inhibitor, before exposure to ethanol. Interestingly, a dual effect of wortmannin
      was observed. Low dose of wortmannin significantly reduced the hepatic TG levels,
      while high dose of wortmannin aggravated ethanol-induced fatty liver. The ratio
      of LC3II/LC3I of wortmannin (1.4 mg/kg bw) group mice was significantly
      increased, while the p62 protein level was significantly decreased compared to
      those of ethanol group, which indicated that wortmannin (1.4 mg/kg bw) might
      suppress the lipid degradation by autophagy. These results supported the
      hypothesis that PI3K/Akt activation might be involved in acute ethanol-induced
      fatty liver, and PI3K/Akt inhibitors might have therapeutic potential for the
      treatment of ethanol-induced fatty liver.

PMID- 22459180
TI  - Intraoperative oculomotor nerve monitoring predicts outcome following clipping of
      posterior communicating artery aneurysms.
AB  - Valid parameters do not exist to predict oculomotor nerve palsy (ONP, ptosis
      and/or diplopia) intraoperatively. In 49 operations involving 46 patients with
      posterior communicating artery aneurysms, the oculomotor nerves were stimulated
      after the aneurysms were clipped. A quantitative analysis of evoked compound
      muscle action potential (CMAP) parameters (stimulus threshold, amplitude and
      latency) from the levator palpebrae superioris (LPS) muscle was performed.
      Absolute values of CMAP amplitude statistically correlated with initial and long
      term oculomotor nerve function (ONF) after surgery (p<0.05). In addition,
      subarachnoid hemorrhage (SAH) significantly influenced the CMAP threshold
      (p<0.05). Monitoring of LPS muscle activity is valuable in the assessment of ONF,
      and the CMAP amplitude of LPS may be a reliable predictor of ONF. Moreover, SAH
      has an impact on the parameters of the LPS CMAP.

PMID- 22459181
TI  - Compromised visually guided motor control in individuals with Alzheimer's
      disease: can reliable distinctions be observed?
AB  - Identifying the multitude of deficits associated with dementia-related illnesses
      such as Alzheimer's disease (AD) presents a significant challenge for many health
      care facilities, particularly as current screening procedures may lack the
      sensitivity to highlight all the relative functional deficits within these
      populations. Although quick assessment screening tools, such as the Mini Mental
      State Exam (MMSE), have been the mainstay in screening patients worldwide, there
      are limitations to their ability in identifying visuomotor (VM) impairment. Thus,
      the primary objective of this research was to evaluate the presence and level of
      VM ability/deficits in healthy normal controls (NC) and populations with AD. The
      research also aimed to demonstrate that a VM measure can be utilized successfully
      in a busy health care setting. Results showed a clear distinction between the AD
      and NC groups on the VM measure. Large effect size differences were observed
      between groups, particularly as the VM task progressed through its varying
      conditions. In addition, this novel VM assessment measure demonstrated good
      presentation and speed and was appropriate for frontline staff in a primary
      healthcare setting to undertake further examination of an individual's overall
      visually guided ability/control.

PMID- 22459182
TI  - Anti-stroke prophylaxis--the ethics of collateral damage.
AB  - Prophylactic anticoagulation therapy with agents such as dabigatran etexilate (as
      an alternative to warfarin) promises substantial benefits to both patients and
      monitoring physicians in the treatment of those at high risk of stroke from
      atrial fibrillation. Such treatment has, however, one potentially lethal
      consequence. There is, as yet, no easily administered rapid means of reversal in
      instances of acute surgical emergency. The problems that may then be encountered
      in neurosurgical practice are discussed.

PMID- 22459183
TI  - A prospective study of Gasserian ganglion pulsed radiofrequency combined with
      continuous radiofrequency for the treatment of trigeminal neuralgia.
AB  - We conducted a prospective randomized controlled study to evaluate whether
      continuous radiofrequency (CRF) combined with pulsed radiofrequency (PRF) to the
      Gasserian ganglion (GG) decreases the side effects of CRF while preserving
      efficacy. Sixty patients diagnosed with classic trigeminal neuralgia (TN) were
      treated with either 75 degrees C CRF for 120 s to 180 s (SCRF group), 75 degrees
      C CRF for 240 s to 300 s (LCRF group), or 42 degrees C PRF for 10 minutes (min)
      followed by 75 degrees C CRF for 120 s to 180 s (PCRF group). Patients were
      assessed for pain intensity, quality of life (QOL), and intensity of facial
      dysesthesia before (baseline), and at seven days, three months, six months, and
      12 months after the procedure. The efficacy in pain relief was most significant
      on the seventh day after treatment and there were no significant differences
      between groups. After 12 months, >70% of patients in each group had complete pain
      relief, and the QOL in all three groups had increased significantly compared to
      baseline. The intensity of facial dysesthesia was mildest in the SCRF group and
      most severe in the PCRF group on the seventh day after the procedure, but most
      persistent in the LCRF group. Patients who receive PRF combined with CRF to the
      GG can achieve comparable pain relief to those who receive CRF alone, and shorter
      exposure of CRF could result in less destruction of the target tissue.

PMID- 22459184
TI  - Minimally invasive surgery compared to open spinal fusion for the treatment of
      degenerative lumbar spine pathologies.
AB  - This clinical study prospectively compares the results of open surgery to
      minimally invasive fusion for degenerative lumbar spine pathologies. Eighty-two
      patients were studied (41 minimally invasive surgery [MIS] spinal fusion, 41 open
      surgical equivalent) under a single surgeon (R. J. Mobbs). The two groups were
      compared using the Oswestry Disability Index, the Short Form-12 version 1, the
      Visual Analogue Scale score, the Patient Satisfaction Index, length of hospital
      stay, time to mobilise, postoperative medication and complications. The MIS
      cohort was found to have significantly less postoperative pain, and to have met
      the expectations of a significantly greater proportion of patients than
      conventional open surgery. The patients who underwent the MIS approach also had
      significantly shorter length of stay, time to mobilisation, lower opioid use and
      total complication rates. In our study MIS provided similar efficacy to the
      conventional open technique, and proved to be superior with regard to patient
      satisfaction, length of hospital stay, time to mobilise and complication rates.

PMID- 22459185
TI  - Comment on: the seroprevalence of Helicobacter pylori and its relationship to
      malaria in Ugandan children.

PMID- 22459186
TI  - Health across early childhood and socioeconomic status: examining the moderating
      effects of differential parenting.
AB  - Variations in parenting within the family (i.e. differential parenting) are
      associated with various domains of child adjustment, whereby disfavoured siblings
      exhibit poorer social and emotional outcomes. To date there is no research
      examining the effects of differential parenting on children's general health, or
      the way in which differential parenting interacts with socioeconomic markers to
      predict general health over time. The present study assessed 501 Canadian
      families at 2 time points separated by 18 months. Differential maternal
      negativity predicted worse health 18 months later. Moreover, the association
      between maternal education and child health was strongest when children were also
      exposed to high levels of differential negativity. Findings indicate that
      multiple forms of social disadvantage (i.e. between families and between
      siblings) can operate independently or in a cumulative fashion to predict health
      across early childhood.

PMID- 22459187
TI  - Interrelatedness of child health, protection and well-being: an application of
      the SAFE model in Rwanda.
AB  - This study examines the core components of children's basic security and well
      being in order to examine issues central to improving child protection in Rwanda.
      Sources of data included 15 focus groups with adults, 7 focus groups with
      children ages 10-17, and 11 key informant interviews with child protection
      stakeholders, including representatives from international NGOs, community-based
      groups, and the Rwandan Government, all of which took place in April and May of
      2010. Participants painted a complex picture of threats to children's basic
      security in Rwanda. Three key themes were pervasive across all interviews: (1)
      deterioration of social and community cohesion in post-genocide Rwanda; (2) the
      cascading effects of poverty; and (3) the impact of caregiver illness and death
      on the caregiving environment. Consistent with the SAFE (Safety/freedom from
      harm; Access to basic physiological needs and healthcare; Family and connection
      to others; Education and economic security) model of child protection,
      participants rarely elaborated on a child protection threat independent of other
      basic security needs and rights. Findings suggest a need for integrated
      approaches to child protection that recognize this interrelatedness and extend
      beyond issue-specific child protection responses. This study contributes to a
      growing body of work highlighting the interrelated nature of child protection
      threats and the implications of adaptive and dangerous survival strategies that
      children and families engage in to meet their basic security needs. Analysis of
      this interrelatedness provides a roadmap for improving policies and implementing
      integrated and robust child protection strategies in Rwanda and other settings.

PMID- 22459189
TI  - The effect of differential eligibility for free GP services on GP utilisation in
      Ireland.
AB  - Internationally, there is extensive empirical evidence that a strong primary care
      led health system is associated with improved health outcomes, increased quality
      of care, decreased health inequalities and lower overall health-care costs.
      Within primary care, factors influencing access to, and utilisation of, general
      practitioner (GP) services have been widely examined and this paper focuses on
      the role of user financial incentives. In particular, user charges for health
      care have been observed to deter health-care utilisation. Relative to other
      countries, the Irish health-care system is unusual in that the majority of the
      population are required to pay out-of-pocket for GP care. However, in 2005 the
      Irish government extended eligibility for free GP care to a further small subset
      of the population. Using micro-data from a nationally representative survey of
      the population in 2007, this paper analyses the impact of differential coverage
      of free GP services on GP utilisation in Ireland. Results from multivariate
      regression analysis indicate that GP utilisation is significantly more likely in
      the context of free GP care, controlling for a range of demographic, socio
      economic and health factors. Interpretation of the results for the new category
      of coverage is complicated by possible pent-up demand and selection effects.

PMID- 22459188
TI  - 'Worse than HIV' or 'not as serious as other diseases'? Conceptualization of
      cervical cancer among newly screened women in Zambia.
AB  - Invasive cervical cancer is the second most common cancer among women worldwide,
      with approximately 85% of the disease burden occurring in developing countries.
      To date, there have been few systematic efforts to document African women's
      conceptualization of cervical cancer after participation in a visual inspection
      with acetic acid (VIA)-based "see and treat" cervical cancer prevention program.
      In this study, conducted between September, 2009-July, 2010, focus groups and in
      depth interviews were conducted with 60 women who had recently undergone cervical
      cancer screening at a government-operated primary health care clinic in Lusaka,
      Zambia. Interviewers elicited participants' causal representations of cervical
      cancer, associated physical signs and symptoms, perceived physical and
      psychological effects, and social norms regarding the disease. The lay model of
      illness causation portrayed by participants after recent exposure to program
      promotion messages departed in several ways from causal models described in other
      parts of the world. However, causal conceptualizations included both lay and
      biomedical elements, suggesting a possible shift from a purely traditional causal
      model to one that incorporates both traditional concepts and recently promoted
      biomedical concepts. Most, but not all, women still equated cervical cancer with
      death, and perceived it to be a highly stigmatized disease in Zambia because of
      its anatomic location, dire natural course, connections to socially-condemned
      behaviors, and association with HIV/AIDS. No substantive differences of disease
      conceptualization existed according to HIV serostatus, though HIV positive women
      acknowledged that their immune status makes them more aware of their health and
      more likely to seek medical attention. Further attention should be dedicated to
      the processes by which women incorporate new knowledge into their representations
      of cervical cancer.

PMID- 22459190
TI  - Effect of surface-functionalized nanoparticles on the elongation phase of beta
      amyloid (1-40) fibrillogenesis.
AB  - The influence of nanoparticles of various sizes and surface functionalities on
      the self-assembling fibrillogenesis of beta-amyloid (1-40) peptide was
      investigated. Functionalized nanoparticles including quantum dots and gold
      nanoparticles were co-incubated with monomeric Abeta(1-40) peptides under seed
      mediated growth method to study their influences on the elongation phase of the
      fibrillogenesis. It is observed that charge-to-surface area ratio of the
      nanoparticles and the functional moiety and electrostatic charges of the
      conjugated ligands on the particle surfaces took crucial regulatory role in the
      Abeta(1-40) fibrillogenesis.

PMID- 22459191
TI  - In vivo renal clearance, biodistribution, toxicity of gold nanoclusters.
AB  - Gold nanoparticles have shown great prospective in cancer diagnosis and therapy,
      but they can not be metabolized and prefer to accumulate in liver and spleen due
      to their large size. The gold nanoclusters with small size can penetrate kidney
      tissue and have promise to decrease in vivo toxicity by renal clearance. In this
      work, we explore the in vivo renal clearance, biodistribution, and toxicity
      responses of the BSA- and GSH-protected gold nanoclusters for 24 h and 28 days.
      The BSA-protected gold nanoclusters have low-efficient renal clearance and only
      1% of gold can be cleared, but the GSH-protected gold nanoclusters have high
      efficient renal clearance and 36% of gold can be cleared after 24 h. The
      biodistribution further reveals that 94% of gold can be metabolized for the GSH
      protected nanoclusters, but only less than 5% of gold can be metabolized for the
      BSA-protected nanoclusters after 28 days. Both of the GSH- and BSA-protected gold
      nanoclusters cause acute infection, inflammation, and kidney function damage
      after 24 h, but these toxicity responses for the GSH-protected gold nanoclusters
      can be eliminated after 28 days. Immune system can also be affected by the two
      kinds of gold nanoclusters, but the immune response for the GSH-protected gold
      nanoclusters can also be recovered after 28 days. These findings show that the
      GSH-protected gold nanoclusters have small size and can be metabolized by renal
      clearance and thus the toxicity can be significantly decreased. The BSA-protected
      gold nanoclusters, however, can form large compounds and further accumulate in
      liver and spleen which can cause irreparable toxicity response. Therefore, the
      GSH-protected gold nanoclusters have great potential for in vivo imaging and
      therapy, and the BSA-protected gold nanoclusters can be used as the agent of
      liver cancer therapy.

PMID- 22459192
TI  - The effects of intrathecal injection of a hyaluronan-based hydrogel on
      inflammation, scarring and neurobehavioural outcomes in a rat model of severe
      spinal cord injury associated with arachnoiditis.
AB  - Traumatic spinal cord injury (SCI) comprises a heterogeneous condition caused by
      a complex array of mechanical forces that damage the spinal cord - making each
      case somewhat unique. In addition to parenchymal injury, a subset of patients
      experience severe inflammation in the subarachnoid space or arachnoiditis, which
      can lead to the development of fluid-filled cavities/syringes, a condition called
      post-traumatic syringomyelia (PTS). Currently, there are no therapeutic means to
      address this devastating complication in patients and furthermore once PTS is
      diagnosed, treatment is often prone to failure. We hypothesized that reducing
      subarachnoid inflammation using a novel bioengineered strategy would improve
      outcome in a rodent model of PTS. A hydrogel of hyaluronan and methyl cellulose
      (HAMC) was injected into the subarachnoid space 24 h post PTS injury in rats.
      Intrathecal injection of HAMC reduced the extent of fibrosis and inflammation in
      the subarachnoid space. Furthermore, HAMC promoted improved neurobehavioural
      recovery, enhanced axonal conduction and reduced the extent of the lesion as
      assessed by MRI and histomorphometric assessment. These findings were
      additionally associated with a reduction in the post-traumatic parenchymal
      fibrous scar formation as evidenced by reduced CSPG deposition and reduced IL
      1alpha cytokine levels. Our data suggest that HAMC is capable of modulating
      inflammation and scarring events, leading to improved functional recovery
      following severe SCI associated with arachnoiditis.

PMID- 22459193
TI  - The isolation and in situ identification of MSCs residing in loose connective
      tissues using a niche-preserving organ culture system.
AB  - Mesenchymal stem cells (MSCs) have been discovered in a multitude of organs, but
      their distribution and identity are still uncertain. Furthermore, loose
      connective tissue (LCT) is dispersed throughout virtually all organs, but its
      biological role in tissue homeostasis is unclear. Here, we describe a unique
      organ culture system to explore the omnipresence and in situ identity of MSCs
      among the LCTs. This culture system included the use of the fibrin hydrogel
      coupled with dynamic culture conditions, using native LCTs obtained from various
      organs as starting materials. This culture allowed MSC outgrowth into the
      hydrogel to be robustly supported, while maintaining the structural integrity of
      LCTs during in vitro culture. Subcultured outgrown cells fulfilled the minimal
      requirements for defining MSCs on the basis of clonogenicity, multipotency, and
      immunophenotypic characteristics. In vitro label-retaining assay demonstrated
      that the numbers of mobilized and proliferated cells in situ increased in the
      pericapillary region and expressed both MSCs and pericytes markers, indicating
      that the in situ identity of MSCs represents a certain population of
      pericapillary pericytes. Our results indicate that this culture system affords a
      unique strategy for both isolating MSCs and recapitulating their niche in LCTs.

PMID- 22459194
TI  - Sustained release of proteins from high water content supramolecular polymer
      hydrogels.
AB  - Self-assembled hydrogels with extremely high water content (up to 99.5%) and
      highly tunable mechanical properties were prepared from renewable cellulose
      derivatives. These hydrogels are easily processed and the simplicity of their
      preparation, their availability from inexpensive renewable resources, and the
      tunability of their mechanical properties are distinguishing for important
      biomedical applications. The protein release characteristics were investigated to
      determine the effect of both the protein molecular weight and polymer loadings of
      the hydrogels on the protein release rate. Extremely sustained release of bovine
      serum albumin is observed over the course of 160 days from supramolecular
      hydrogels containing only 1.5 wt% polymeric constituents. This sustained release
      far surpasses the current state of the art for protein release from a hydrogel,
      highlighting these materials as important potential candidates for sustained
      therapeutic applications.

PMID- 22459195
TI  - Pharmacokinetics & tissue distribution of temperature-sensitive liposomal
      doxorubicin in tumor-bearing mice triggered with mild hyperthermia.
AB  - Drug-loaded temperature-sensitive liposomes (TSL) in combination with
      hyperthermia (HT) have attracted considerable attention for cancer treatment.
      Different TSL systems have been designed with wide variations in their
      temperature sensitivity and drug release profile. Low temperature-sensitive
      liposomes (LTSL) with the capacity for ultrafast drug release, traditional
      temperature-sensitive (TTSL) with intermediate drug release properties and non
      temperature-sensitive liposomes (NTSL) (no drug release) were dual-labeled with
      (3)H-cholesteryl hexadecyl ether ((3)H-CHE) lipid and loaded with (14)C
      doxorubicin ((14)C-Dox). Their blood profile, serum stability, tissue
      distribution and tumor localization (B16F10 melanoma) were studied after
      intravenous administration and mild HT treatment. LTSL showed higher affinity for
      the liver compared to TTSL and NTSL which were uptaken mainly by spleen. Under
      normal conditions (no HT) Dox leakage from liposomes was expected, higher for
      LTSL, less for TTSL and minimal for NTSL. Localized HT did not affect the overall
      blood circulation or organ accumulation for all TSL studied. Since LTSL showed
      ultrafast Dox release kinetics at 42  degrees C, the highest drug accumulation in
      tumors was observed using this system immediately after HT, however decreased
      significantly after 24 h. In contrast, TTSL and NTSL showed 2-3 fold increase in
      both liposome and Dox levels that indicated enhanced tumor extravasation of
      intact Dox-loaded liposomes during the 60 min HT applications. More
      interestingly, high levels of drug tumor accumulation were achieved 24 h post-HT.
      This study offers further understanding on how the mechanisms of drug release
      from temperature-sensitive liposomes affect their pharmacological profile under
      mild hyperthermia.

PMID- 22459196
TI  - The effects of sub-lethal concentrations of silver nanoparticles on inflammatory
      and stress genes in human macrophages using cDNA microarray analysis.
AB  - Because of the limited information on size-dependent particle-mediated effects,
      the present study was conducted to determine if the changes in induced protein
      expression between 5 nm silver nanoparticles and 100 nm particles after exposure
      to sub-lethal concentrations. A total of 28,000 cDNA profiles were screened using
      5 nm silver nanoparticles and 100 nm silver nanoparticles in a macrophage cell
      line. Based on results obtained from cDNA microarray we also assessed protein
      levels of hemeoxygenase-1 (HO-1), heat shock protein-70 (HSP-70) and interleukin
      8 (IL-8), which were shown to significantly increase. Together with results
      obtained using N-acetylcystein (NAC), we were able to clearly show that low level
      and early stage exposure to 5 nm silver nanoparticles, but not 100 nm, induces
      expression of IL-8 as well as stress genes against reactive oxygen species (ROS).
      Therefore, we provide important data to understand and identify the early effects
      of silver nanoparticles on the immune system.

PMID- 22459197
TI  - Influence of decellularized matrix derived from human mesenchymal stem cells on
      their proliferation, migration and multi-lineage differentiation potential.
AB  - Developing biomaterials to promote stem cell proliferation and differentiation is
      a critical requirement in tissue engineering and regeneration. Extracellular
      matrix (ECM) derived from mesenchymal stem cells (MSCs) has recently been shown
      to be able to maintain the differentiation potential of MSCs during culture
      expansion and to restore the activities of aging MSCs, suggesting that MSC ECM
      (MECM) may be a suitable culture substrate to enhance the bioactivity of
      biomaterial scaffolds for MSCs. This investigation aims to characterize the
      biological nature and specificity of the influence of the MECM on MSCs. Native
      ECM produced by human MSC in vitro was extracted in urea, and the residual pellet
      was further processed with pepsin digestion (denoted as U-MECM and HP-MECM,
      respectively). The MECM products were then coated as a substrate on standard
      tissue culture plastic, and the behavior of MSCs seeded on the coated surfaces
      was studied. Our results showed that U-MECM coating dramatically accelerated MSC
      proliferation, attachment, spread, migration and multi-lineage differentiation
      (i.e., osteogenesis and adipogenesis), compared to collagen type I and HP-MECM
      coating. Non-collagenous proteins are likely the bioactive components in U-MECM,
      as MSCs cultured on collagen type I and HP-MECM showed similar biological
      activities, and collagen type I appeared to be the major protein components
      remaining in HP-MECM based on SDS-PAGE. These findings support the biological
      utility of MECM in the formulation of biomaterial scaffolds to enhance MSC
      bioactivities, including proliferation, migration and multi-lineage
      differentiation, for tissue regeneration applications.

PMID- 22459198
TI  - The descriptive epidemiology of female breast cancer: an international comparison
      of screening, incidence, survival and mortality.
AB  - BACKGROUND: This paper presents the latest international descriptive
      epidemiological data for invasive breast cancer amongst women, including
      incidence, survival and mortality, as well as information on mammographic
      screening programmes. RESULTS: Almost 1.4 million women were diagnosed with
      breast cancer worldwide in 2008 and approximately 459,000 deaths were recorded.
      Incidence rates were much higher in more developed countries compared to less
      developed countries (71.7/100,000 and 29.3/100,000 respectively, adjusted to the
      World 2000 Standard Population) whereas the corresponding mortality rates were
      17.1/100,000 and 11.8/100,000. Five-year relative survival estimates range from
      12% in parts of Africa to almost 90% in the United States, Australia and Canada,
      with the differential linked to a combination of early detection, access to
      treatment services and cultural barriers. Observed improvements in breast cancer
      survival in more developed parts of the world over recent decades have been
      attributed to the introduction of population-based screening using mammography
      and the systemic use of adjuvant therapies. CONCLUSION: The future worldwide
      breast cancer burden will be strongly influenced by large predicted rises in
      incidence throughout parts of Asia due to an increasingly "westernised"
      lifestyle. Efforts are underway to reduce the global disparities in survival for
      women with breast cancer using cost-effective interventions.

PMID- 22459199
TI  - Metastatic pancreatic neuroendocrine tumors (pNET): placing current findings into
      perspective.
AB  - Progress during the past 3 decades in the treatment of advanced neuroendocrine
      tumors (NET) has been slow, despite a substantial increase in the incidence of
      NET at all primary sites and stages of disease. In the United States, the annual
      incidence of pancreatic NET (pNET) was estimated as 0.32 per 100,000 people in
      2004. Until recently, there were few available therapies for the treatment of
      patients with advanced pNET. Nonetheless, substantial strides have been made
      within the past several years. In 2011, 2 new systemic therapies (everolimus and
      sunitinib) were approved by the US Food and Drug Administration (FDA) for the
      treatment of patients with advanced pNET, based on recently published results
      from 2 phase III studies. Additions to the pNET treatment arsenal significantly
      expanded options for clinicians who treat these patients. However, important
      differences between the key clinical studies existed, preventing optimal direct
      comparison of the study results. Therefore, the clinical implications of these
      study results continue to be debated. The following commentary briefly summarizes
      the background of NET and provides an overview of available options, highlighting
      the important findings of the 2 pivotal studies. In this review, the data
      supporting the use of everolimus and sunitinib in advanced pNET are reviewed, and
      the incorporation of these targeted therapies into a pNET treatment algorithm is
      further discussed.

PMID- 22459200
TI  - An overview of neoadjuvant chemotherapy in the multimodality treatment of
      malignant pleural mesothelioma.
AB  - Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis
      and increasing incidence in industrialized countries because of the previous
      widespread exposure to asbestos fibres and to the long lag period from time of
      exposure and the diagnosis of the disease. MPM shows high refractoriety to
      systemic treatment, single-modality treatment was generally ineffective and did
      not achieve higher results than supportive care. The incidence of local and
      distant recurrences after surgery remains high and that was the reason for many
      centres to perform combined treatments. In the attempt of reducing the incidence
      of local recurrences, a multimodality approach with surgery followed by adjuvant
      radiotherapy was explored. Extrapleural pneumonectomy (EPP) allows higher doses
      of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity and the
      results of this approach is a significant reduction of loco-regional relapses;
      although, extrathoracic metastasis represent a major problem in the management of
      the disease because of the impact on overall survival. The success with surgical
      resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the
      impetus for several groups to apply this strategy in MPM aiming at reducing the
      incidence of distant relapse after surgery. Platinum-based chemotherapy plus
      gemcitabine or pemetrexed for 3-4 cycles followed by surgery and postoperative
      high-dose radiotherapy showed the best results in terms of overall and
      progression free survival. This review will focus on the main clinical studies
      and overview the results of different chemotherapy regimens in the neoadjuvant
      treatment of MPM.

PMID- 22459201
TI  - Examining the effect of dl-3,4-methylenedioxymethamphetamine (MDMA) and
      methamphetamine on the Standardized Field Sobriety Tests.
AB  - dl-3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine are commonly used
      illicit drugs that are thought to impair driving ability. The Standardized Field
      Sobriety Tests (SFSTs) are utilized widely to detect impairment associated with
      drugs other than alcohol in drivers, although limited evidence concerning MDMA
      and methamphetamine consumption on SFST performance exists. The aim of this study
      was to evaluate whether the SFSTs were a sensitive measure for identifying the
      presence of the specific isomer d-methamphetamine and MDMA. In a double-blind,
      within-subject, counter-balanced and placebo-controlled study, 58 healthy and
      abstinent recreational drugs users were administered three treatments: 100mg of
      MDMA, 0.42 mg/kg d-methamphetamine, and placebo. For each condition the SFSTs
      were administered at 4 and 25 h post treatment. d-methamphetamine was not found
      to significantly impair SFST performance unlike MDMA, which significantly
      impaired SFST performance in comparison to placebo with 22% of the sample failing
      the test at the 4h testing time-point. No differences were observed at the 25 h
      testing time-point for any of the conditions. It was concluded that the SFSTs are
      not efficient in identifying the presence of low level d-methamphetamine, and are
      significantly better at detecting the presence of MDMA at the levels assessed.

PMID- 22459202
TI  - A preliminary study of incisor exfoliation as an estimator of the postmortem
      interval using accumulated degree days.
AB  - This research shows the exfoliation of the anterior dentition has significant
      potential to aid in establishing the minimum length of the post-mortem interval.
      Accumulated degree days (ADD) were used to quantify the decomposition of the
      periodontal ligament, represented by post-mortem exfoliation of the incisors.
      After subjects were removed subsequent to disturbance by scavengers and time
      limitations on the study, the final sample size was 36 incisors from the maxillae
      and mandibles of seven pigs (Sus scrofa). Average daily temperature was
      calculated using hourly temperature data recorded using DS1921G thermochrons for
      the duration of the project (June 14-December 17, 2008). During this period, six
      teeth (16.7%) were exfoliated. ADD for these six teeth ranged from 1539.7 
      degrees C to 2006.7  degrees C. The average ADD required for exfoliation was
      1788.0  degrees C (SD=198.1  degrees C). No differences in ADD required for
      exfoliation were observed between the maxillary and mandibular teeth (t=2.085;
      p=0.128).

PMID- 22459203
TI  - Generalisability of the results of the Dutch-Belgian randomised controlled lung
      cancer CT screening trial (NELSON): does self-selection play a role?
AB  - The degree of self-selection in the Dutch-Belgian randomised controlled lung
      cancer screening trial (NELSON) was determined to assess the generalisability of
      the study results. 335,441 (mainly) men born in 1928-1953 received a
      questionnaire. Of the respondents (32%), eligible subjects were invited to
      participate (19%). Fifty-five percent gave informed consent and was randomised.
      Background characteristics were compared between male respondents on the first
      questionnaire (n = 92,802), eligible subjects among them (n = 18,570) and those
      randomised (n = 10,627) and Statistics Netherlands 2002-2005 (SN) (n = 5289) or
      GLOBE study-data (Dutch cohort) (n = 696). Initial respondents were less likely
      to be highly educated (OR(adj) = 0.84; 95% CI: 0.74-0.96) and comprised of
      significantly less current smokers (OR(adj) = 0.65; 95% CI: 0.61-0.69) compared
      to the general population. These current smokers smoked more heavily (OR(adj) =
      1.23; 95% CI: 1.10-1.37), but for a shorter time-period (respondents: 31, SN: 42
      years, p < 0.001). Age, general health, BMI, alcohol use and cancer prevalence
      were comparable. The randomised population was younger (Age 50-65) (randomised
      subjects: 85.3%, SN: 72% (p < 0.01)) comprised of more heavy current smokers (OR
      = 2.08; 95% CI: 1.75-2.44), that smoked for a shorter period of time (randomised
      subjects: 37, SN_selection: 42 years (p < 0.001)). Both the respondents (32%) of
      the first questionnaire as well as the randomised population of the NELSON trial
      appeared to differ slightly on smoking characteristics, but the differences were
      limited and probably balance each other. Results of the NELSON trial will be
      roughly applicable to the Dutch and probably other populations that fulfil our
      selection criteria.

PMID- 22459204
TI  - Exploratory analysis of activation of PTEN-PI3K pathway and downstream proteins
      in malignant pleural mesothelioma (MPM).
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm
      with elevated AKT/mTOR activity. We aimed to identify the expression and
      phosphorylation status of PTEN, PI3K and downstream signaling in MPM. PATIENTS
      AND METHODS: Thirty consecutive MPM patients were identified. Clinical data
      analyzed: sex, age, histology, performance status (PS), white blood count, and
      neutrophil-lymphocyte ratio (NLR). Paraffin-embedded biopsies were used for
      immunohistochemical analysis. RESULTS: Overexpression of PTEN, pMAPK, mTOR, pAKT,
      4E-BP1, p4E-BP1, eIF-4E, peIF-4E, p-S6 and FOXO3a in MPM was found in 90%, 100%,
      93.3%, 80%, 100%, 43.3%, 96.7%, 100%, 63.3% and 100% of tumors respectively.
      There was a significant correlation between low pS6 protein expression and longer
      progression free survival (PFS: 7.9 vs 5.6 months; p = 0.04) and overall survival
      (OS: 23.4 vs 5.6 months; p = 0.05). Patients with concomitant low expression of
      pS6 and p4E-BP1 and overexpression of FOXO3a had significantly better prognosis
      (34.6 vs 1.9 months; p = 0.004). In multivariate analysis, histology and NLR were
      independent prognostic factors (p = 0.02 and p = 0.04 respectively), but pS6 only
      showed a trend (p = 0.8). CONCLUSIONS: This study shows PI3K pathway and
      downstream proteins in MPM are frequently activated and provides prognostic
      information. The role of PI3K pathway is worth of prospective validation in
      future studies on MPM.

PMID- 22459205
TI  - Hepatocellular proliferation and hepatocarcinogen bioactivation in mice with diet
      induced fatty liver and obesity.
AB  - Human liver cancer is in part associated with obesity and related metabolic
      diseases. The present study was undertaken in a mouse model of diet-induced
      obesity (DIO) and hepatic steatosis, conditions which can be associated with
      hepatic neoplasia, to determine whether the rates of cell proliferation or
      hepatocarcinogen bioactivation were altered in ways which could facilitate
      hepatocarcinogenesis. DIO mice were generated by feeding C57BL/6 (B6) male mice a
      high-fat diet beginning at 4 weeks of age; age-matched conventional lean (LEAN)
      B6 mice fed a low fat diet (10% Kcal from fat) were used for comparison. Groups
      of 28 week old DIO and LEAN mice were dosed with the bioactivation-dependent DNA
      reactive hepatocarcinogen 2-acetylaminofluorene (AAF), at 2.24 or 22.4 mg/kg,
      given by gavage 3 times per week for 31 days, or received no treatment (DIO and
      LEAN control groups). Compared with the LEAN control group, the DIO control group
      had a higher mean body weight (16.5 g), higher mean absolute (1.4 g) and mean
      relative (25.5%) liver weights, higher (394%) liver triglyceride concentrations,
      and an increased incidence and severity of hepatocellular steatosis at the end of
      the dosing phase. The DIO control group also had a higher mean hepatocellular
      replicating fraction (31% increase, determined by proliferating cell nuclear
      antigen immunohistochemistry). Hepatocarcinogen bioactivation, based on formation
      of AAF DNA adducts as measured by nucleotide (32)P-postlabeling, was similar in
      both DIO and LEAN AAF-dosed groups. Thus, hepatocellular proliferation, but not
      hepatocarcinogen bioactivation, was identified as an alteration in livers of DIO
      mice which could contribute to their susceptibility to hepatocarcinogenesis.

PMID- 22459207
TI  - Peptide tyrosine tyrosine levels are increased in patients with urea cycle
      disorders.
AB  - Nutritional management is essential for patients with inborn errors of
      metabolism, such as urea cycle disorders (UCDs). Lack of appetite is common in
      these patients and can lead to underconsumption of calories, catabolism, and
      subsequently loss of metabolic control. The etiology of anorexia in these
      patients is largely unexplored. The neuroendocrine hormone peptide tyrosine
      tyrosine (PYY), secreted postprandially from endocrine cells of the ileum and
      colon, induces feelings of satiety and decreases food intake. While plasma PYY
      levels have been characterized in a number of populations, they have not been
      examined in UCD patients. In a retrospective study, plasma PYY concentrations
      were measured in UCD (n=42) patients and controls (n=28) via an ELISA to
      determine if levels of this anorexigenic hormone are altered in this patient
      population. Median PYY levels were significantly higher in UCD patients compared
      to controls (p=3.5*10(-5)). Body mass index was significantly associated with
      increased PYY levels in controls (p=0.02), while UCD diagnosis subtype was
      associated with PYY levels (p=1*10(-3)) in cases. Median PYY levels were
      significantly lower in ornithine carbamoyltransferase deficient patients compared
      with all other UCD subtypes (p=9*10(-3)), but significantly higher compared to
      controls (p=1.6*10(-3)). Overall, this study demonstrates that UCD cases have
      increased PYY levels compared to controls, suggesting that regulation of PYY may
      be altered in these patients. These observations may lead to a better
      understanding of the development of anorexia in UCD patients.

PMID- 22459206
TI  - Observations regarding retinopathy in mitochondrial trifunctional protein
      deficiencies.
AB  - Although the retina is thought to primarily rely on glucose for fuel, inherited
      deficiency of one or more activities of mitochondrial trifunctional protein
      results in a pigmentary retinopathy leading to vision loss. Many other enzymatic
      deficiencies in fatty acid oxidation pathways have been described, none of which
      results in retinal complications. The etiology of retinopathy among patients with
      defects in trifunctional protein is unknown. Trifunctional protein is a
      heteroctomer; two genes encode the alpha and beta subunits of TFP respectively,
      HADHA and HADHB. A common mutation in HADHA, c.1528G>C, leads to a single amino
      acid substitution, p. Glu474Gln, and impairs primarily long-chain 3-hydroxyacyl
      CoA dehydrogenase (LCHAD) activity leading to LCHAD deficiency (LCHADD). Other
      mutations in HADHA or HADHB often lead to significant reduction in all three
      enzymatic activities and result in trifunctional protein deficiency (TFPD).
      Despite many similarities in clinical presentation and phenotype, there is
      growing evidence that they can result in different chronic complications. This
      review will outline the clinical similarities and differences between LCHADD and
      TFPD, describe the course of the associated retinopathy, propose a
      genotype/phenotype correlation with the severity of retinopathy, and discuss the
      current theories about the etiology of the retinopathy.

PMID- 22459209
TI  - Synthesis of novel 9-O-N-aryl/aryl-alkyl amino carbonyl methyl substituted
      berberine analogs and evaluation of DNA binding aspects.
AB  - This manuscript describes the design and synthesis of three 9-O substituted
      analogs of plant alkaloid berberine to enhance the DNA binding affinity. Three
      analogs of berberine with aryl/aryl-alkyl amino carbonyl methyl substituent at
      the 9-position of the isoquinoline chromophore were synthesized and characterized
      by NMR ((1)HNMR and (13)C NMR) and mass spectroscopy. The products were evaluated
      for their binding to calf thymus DNA by a wide variety of techniques like
      spectrophotometry, spectrofluorimetry, circular dichroism, thermal melting,
      viscosity and isothermal titration calorimetry. The results revealed that these
      analogs showed more than six times higher binding affinity to DNA compared to
      berberine. From fluorescence and absorbance studies it was inferred that all the
      analogs bound to DNA non-cooperatively in contrast to the cooperative binding of
      the parent alkaloid berberine. The viscosity and ferrocyanide quenching
      experiments confirmed that the analogs are stronger intercalative binders to DNA
      useful for potential biological applications. Stronger binding of the analogs was
      also inferred from circular dichroism studies and thermal melting experiments.
      Thermodynamics of the binding from isothermal titration calorimetry experiments
      revealed an entropy driven binding for these analogs compared to the enthalpy
      driven binding of berberine. The small but negative heat capacity change of the
      analogs along with the significant enthalpy-entropy compensation phenomenon
      observed established the involvement of multiple weak noncovalent interactions in
      the binding process. A comparative study also revealed that the spacer length is
      also significant in modulating the DNA binding affinities.

PMID- 22459208
TI  - Novel epigallocatechin gallate (EGCG) analogs activate AMP-activated protein
      kinase pathway and target cancer stem cells.
AB  - AMP-activated protein kinase (AMPK) is a critical monitor of cellular energy
      status and also controls processes related to tumor development, including cell
      cycle progression, protein synthesis, cell growth and survival. Therefore AMPK as
      an anti-cancer target has received intensive attention recently. It has been
      reported that the anti-diabetic drug metformin and some natural compounds, such
      as quercetin, genistein, capsaicin and green tea polyphenol epigallocatechin
      gallate (EGCG), can activate AMPK and inhibit cancer cell growth. Indeed, natural
      products have been the most productive source of leads for the development of
      anti-cancer drugs but perceived disadvantages, such as low bioavailability and
      week potency, have limited their development and use in the clinic. In this study
      we demonstrated that synthetic EGCG analogs 4 and 6 were more potent AMPK
      activators than metformin and EGCG. Activation of AMPK by these EGCG analogs
      resulted in inhibition of cell proliferation, up-regulation of the cyclin
      dependent kinase inhibitor p21, down-regulation of mTOR pathway, and suppression
      of stem cell population in human breast cancer cells. Our findings suggest that
      novel potent and specific AMPK activators can be discovered from natural and
      synthetic sources that have potential to be used for anti-cancer therapy in the
      clinic.

PMID- 22459210
TI  - Exogenous fluorescent tracer agents based on pegylated pyrazine dyes for real
      time point-of-care measurement of glomerular filtration rate.
AB  - Novel pyrazine carboxamides bearing hydrophilic poly(ethylene glycol) (PEG)
      moieties were designed, synthesized, and evaluated for use as fluorescent
      glomerular filtration rate (GFR) tracer agents. Among these, compounds 4d and 5c
      that contain about 48 ethylene oxide units in the PEG chain exhibited the most
      favorable physicochemical and renal clearance properties. In vitro studies show
      that these two compounds have low plasma protein binding, a necessary condition
      for renal excretion. In vivo animal model results show that 4d and 5c have a
      higher urine recovery of the injected dose than iothalamate (a commonly
      considered gold standard GFR agent). Pharmacokinetic studies show that these two
      compounds exhibit a plasma clearance equivalent to iothalamate, but with a faster
      (i.e. lower) terminal half-life than iothalamate (possibly from restricted
      distribution into the extracellular space due to large molecular size and
      hydrodynamic volume). Furthermore, the plasma clearance of 4d and 5c remained
      unchanged upon blockage of the tubular secretion pathway with probenecid, a
      necessary condition for establishment of clearance via glomerular filtration
      exclusively. Finally, noninvasive real-time monitoring of this class of compounds
      was demonstrated by pharmacokinetic clearance of 5c by optical measurements in
      rat model, which correlates strongly with plasma concentration of the tracer.
      Hence, 4d and 5c are promising candidates for translation to the clinic as
      exogenous fluorescent tracer agents in real-time point-of-care monitoring of GFR.

PMID- 22459211
TI  - Compounds of Alpinia katsumadai as potential efflux inhibitors in Mycobacterium
      smegmatis.
AB  - Efflux pumps are one of the well established mechanisms that contribute to
      antibiotic resistance in bacteria, such as mycobacteria. As a result, the
      identification of efflux pump inhibitors is an attractive target in antimicrobial
      therapy. The isolated compounds, three diarylheptanoids, trans,trans-1,7
      diphenylhepta-4,6-dien-3-one (1), (5R)-trans-1,7-diphenyl-5-hydroxyhept-6-en-3
      one (2), (3S,5S)-trans-1,7-diphenylhept-1-ene-3,5-diol (3) and the flavonoid
      pinocembrin (4), from Alpinia katsumadai, Zingiberaceae, were examined for their
      antimycobacterial activity and their synergistic effects with different
      antibiotics against M. smegmatis mc(2) 155. Furthermore, these compounds were
      evaluated as potential EtBr efflux inhibitors. Although they showed weak
      antimycobacterial activities (MIC >= 64 mg/L), especially compound 1 revealed a
      significant activity on the EtBr accumulation and efflux as well as a synergistic
      effect in combination with rifampicin.

PMID- 22459212
TI  - Synthesis and biological evaluation of novel human Pin1 inhibitors with
      benzophenone skeleton.
AB  - A series of novel benzophenone derivatives were prepared and their inhibitory
      activities were evaluated on hPin1. Of all the synthesized compounds, the most
      active compound displayed inhibitory activities with an IC(50) value of 5.99
      MUmol/L. Preliminary structure-activity relationships were analyzed in details
      and the binding mode of the titled compounds was predicted using FlexX algorithm.
      The results of this research will shed light on further design and optimization
      of novel small molecule Pin1 inhibitors.

PMID- 22459213
TI  - Design, synthesis, and pharmacological evaluation of benzamide derivatives as
      glucokinase activators.
AB  - A series of benzamide derivatives were assembled by using the privileged-fragment
      merging (PFM) strategy and their SAR studies as glucokinase activators were
      described. Compounds 5 and 16b were identified having a suitable balance of
      potency and activation profile. They showed EC(50) values of 28.3 and 44.8 nM,
      and activation folds of 2.4 and 2.2, respectively. However, both compounds
      displayed a minor reduction in plasma glucose levels on imprinting control region
      (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these
      two compounds.

PMID- 22459214
TI  - Understanding the attitudes of hospital pharmacists to reporting medication
      incidents: a qualitative study.
AB  - BACKGROUND: The attitudes of doctors, nurses, and midwives to reporting errors in
      health care have been extensively studied, but there is very limited literature
      considering pharmacists' attitudes to medication error reporting schemes, in
      particular in hospitals. OBJECTIVES: To explore and understand the attitudes of
      hospital pharmacists to reporting medication incidents. METHODS: Focus groups
      were conducted with a total of 17 hospital pharmacists from 4 purposively sampled
      hospitals in the North West of England. The recordings of the focus groups were
      transcribed verbatim and subject to thematic analysis using a framework analysis
      approach. RESULTS: Pharmacists agreed that the high prevalence of medication
      errors, especially prescribing errors of omission, has led to an acceptance of
      not using hospital reporting systems. There were different personal thresholds
      for reporting medication errors but pharmacists agreed that the severity of any
      patient harm was the primary reporting driver. Hospital pharmacists had specific
      anxieties about the effects of reporting on interprofessional working
      relationships with doctors and nurses, but felt more confident to report if they
      had previously witnessed positive feedback and system change following an error.
      Existing reporting forms were considered too cumbersome and time consuming to
      complete, as pharmacists felt the need to find and record every possible detail.
      CONCLUSIONS: Hospital pharmacists understood the importance of reporting
      medication incidents, but because of the high number of errors they encounter do
      not report them as often as may be expected. The decision to report was a complex
      process that depended on the severity of patient harm, anxieties about harming
      interprofessional relationships, prior experience of the outcomes from reporting,
      and the perceived effort required to use reporting forms.

PMID- 22459215
TI  - mtDNA variations other than point mutations may also have a role in
      carcinogenesis of lung cancer.

PMID- 22459216
TI  - TRPM8 antagonists and their emerging role in the modulation of pain and
      allodynia.

PMID- 22459217
TI  - Phytonutrients found in fruits and vegetables: ways to encourage their intake.

PMID- 22459218
TI  - Competency is more than a credential.

PMID- 22459219
TI  - Defining processed foods for the consumer.

PMID- 22459220
TI  - Communication and education for families dealing with end-of-life decisions.

PMID- 22459221
TI  - 2011 Lenna Frances Cooper Memorial Lecture: the road to HEaLth is paved with good
      InVentions: of science, sense, and elephense.

PMID- 22459227
TI  - Are krill oil supplements a better source of n-3 fatty acids than fish oil
      supplements?

PMID- 22459228
TI  - Saliva and blood concentration of cefuroxime in patients undergoing maxillofacial
      surgery.
AB  - PURPOSE: To investigate the penetration of cefuroxime into the parotid saliva
      after short-term intravenous administration in patients undergoing various
      maxillofacial surgical procedures. PATIENTS AND METHODS: A total of 12 patients,
      10 males and 2 females, with a mean age of 41 +/- 21.2 years, participated in the
      present study. Each patient received 1.5 g of intravenous cefuroxime every 8
      hours. Blood and parotid saliva samples were collected concomitantly, on the
      third day of therapy, just before the infusion of the first morning dose, and 0.5
      hour after its end. All samples were analyzed using high-performance liquid
      chromatography. RESULTS: The cefuroxime concentration in plasma and saliva before
      infusion was 2.08 +/- 1.05 mg/L and 0.46 +/- 0.33 mg/L, respectively. At 30
      minutes after the end of infusion, the corresponding concentrations were 55.54 +/
      20.24 mg/L and 14.50 +/- 7.85 mg/L. The saliva/plasma ratio was 0.25 +/- 0.18
      before and 0.26 +/- 0.12 after the infusion. CONCLUSIONS: Cefuroxime is excreted
      in saliva in high levels shortly after infusion but is detected in far lower
      levels 8 hours after infusion. Taking into consideration the minimum inhibitory
      concentration values of common pathogens, we have concluded that the saliva
      concentrations of the drug are sufficient against some, but not all, pathogens
      involved in the oral-maxillofacial area.

PMID- 22459229
TI  - Glucose-6-phosphate dehydrogenase deficiency and borderline deficiency:
      association with neonatal hyperbilirubinemia.
AB  - OBJECTIVE: To characterize the occurrence of glucose-6-phosphate dehydrogenase
      (G6PD) deficiency and its association with neonatal hyperbilirubinemia. STUDY
      DESIGN: This study involved an evaluation of G6PD data for 2656 newborns from a
      universal newborn screening program. RESULTS: Mean G6PD activity was 14.2 +/- 3.3
      U/g Hb. Some 2.71% of the newborns were G6PD-deficient, and 1.77% had borderline
      G6PD activity, with male and female predominance, respectively. G6PD deficiency
      was more prevalent in newborns of Sephardic Jew and Muslim Arab backgrounds. The
      infants with G6PD deficiency had higher bilirubin levels at the time of discharge
      from the nursery. Infants with low and borderline G6PD activity were more likely
      to require phototherapy (22.2% and 25.5%, respectively, vs 7.6% of infants with
      normal G6PD activity; P < .005) and to have more referrals for exacerbation of
      jaundice (15.3% and 14.9%, respectively, vs 6.1%; P < .005). Mean G6PD activity
      was higher in preterm infants born at 27-34 weeks gestational age compared with
      those born later (16.3 +/- 1.8 U/g Hb vs 14.8 +/- 2.0 U/g Hb). Based on sex
      distribution and theoretical genetic calculations for the rate of heterozygous
      females, we propose that the range of borderline G6PD activity should be 2-10 U/g
      Hb rather than the currently accepted range of 2-7 U/g Hb. CONCLUSIONS: There is
      association between G6PD deficiency and significant neonatal hyperbilirubinemia.
      Increased risk is also associated with borderline G6PD activity. The suggested
      new range for borderline G6PD activity should enhance the identification of
      females at risk. G6PD activity is higher in preterm infants.

PMID- 22459231
TI  - Reproductive health experiences of women with cardiovascular disease.
AB  - BACKGROUND: Limited research exists exploring contraceptive and pregnancy
      experiences of women with cardiovascular diseases. STUDY DESIGN: We conducted
      semistructured interviews with reproductive-age women with chronic hypertension
      or peripartum cardiomyopathy exploring thoughts and behaviors regarding future
      fertility. Transcribed interviews were coded and analyzed identifying salient
      themes. RESULTS: We interviewed 20 women with chronic hypertension and 10 women
      with peripartum cardiomyopathy. Women described a spectrum of perspectives
      regarding the relationship between disease and fertility: from complete
      disconnect to full integration of diagnosis and future fertility plans.
      Integration of reproductive and cardiovascular health was influenced by and
      reflected in circumstances of diagnosis, pregnancy-related experiences,
      contraception-related experiences and conceptualization of disease risk related
      to reproductive health. CONCLUSIONS: Providers must better understand how women
      perceive and consider their reproductive and cardiovascular health in order to
      optimize contraceptive care of women with cardiovascular disease and help them
      make safe, informed decisions about future fertility.

PMID- 22459230
TI  - The meaning of parenteral hydration to family caregivers and patients with
      advanced cancer receiving hospice care.
AB  - CONTEXT: In the U.S., patients with advanced cancer who are dehydrated or have
      decreased oral intake almost always receive parenteral hydration in acute care
      facilities but rarely in the hospice setting. OBJECTIVES: To describe the meaning
      of hydration for terminally ill cancer patients in home hospice care and for
      their primary caregivers. METHODS: Phenomenological interviews were conducted at
      two time points with 85 patients and 84 caregivers enrolled in a randomized,
      double-blind, controlled trial examining the efficacy of parenteral hydration in
      patients with advanced cancer receiving hospice care in the southern U.S.
      Transcripts were analyzed hermeneutically by the interdisciplinary research team
      until consensus on the theme labels was reached. RESULTS: Patients and their
      family caregivers saw hydration as meaning hope and comfort. Hope was the view
      that hydration might prolong a life of dignity and enhance quality of life by
      reducing symptoms such as fatigue and increasing patients' alertness. Patients
      and caregivers also described hydration as improving patients' comfort by
      reducing pain; enhancing the effectiveness of pain medication; and nourishing the
      body, mind, and spirit. CONCLUSION: These findings differ from traditional
      hospice beliefs that dehydration enhances patient comfort, given that patients
      and their families in the study viewed fluids as enhancing comfort, dignity, and
      quality of life. Discussion with patients and families about their preferences
      for hydration may help tailor care plans to meet specific patient needs.

PMID- 22459232
TI  - Update on and correction to the cost-effectiveness of contraceptives in the
      United States.

PMID- 22459233
TI  - Management of missing strings in users of intrauterine contraceptives.
AB  - BACKGROUND: A common question among health care professionals is how to manage
      nonvisible strings in users of intrauterine contraceptives (IUCs) at repeat
      follow-up visits. This study assessed the position of the IUCs in women who
      consulted repeatedly with nonvisible IUC strings. STUDY DESIGN: The medical
      records of the clinic were reviewed to identify new acceptors and switchers who
      had an IUC inserted between 1990 and 2009. All women were identified whose IUC
      string could not be visualized at the external os of the cervix by the health
      care professional at any given follow-up visit, even after attempting a standard
      maneuver of sweeping the strings from the cervical canal using a cervical brush
      or trying to visualize the strings in the cervical canal using colposcopy. Data
      were also retrieved on the use of ultrasonography and/or pelvic X-ray to assess
      IUC position, as well as data from any subsequent visits at which the IUC strings
      were nonvisible. RESULTS: The medical charts of 14,935 patients using an IUC were
      reviewed, and 750 women (5.0%) presenting for the first time with missing IUC
      strings at any follow-up visit were identified. Ultrasound scans showed the IUC
      to be in situ in 735 cases (98.0%), while 9 women (1.2%) had expelled the device
      and, in 5 cases (0.7%), the device was found in the pelvis following uterine
      perforation. IUC strings were missing on a second occasion in 297 cases. The
      device was found to be in situ in 295 cases (99.3%) and had been expelled in 2
      (0.7%). At subsequent consultations, (between 1 and 18 years after the first
      consultation), strings were missing in 113, 55, 19 and 5 cases. In 111 (98.2%),
      54 (98.2%), 18 (94.7%) and 5 (100%) of these cases, respectively, the IUC was
      found to be in situ, while in the remaining cases, the device had been expelled.
      CONCLUSIONS: Missing IUC strings are an uncommon finding, and ultrasonography
      confirmed that the device was in situ in the majority of these cases. For women
      with persistent missing IUC strings after one ultrasound scan that has verified
      appropriate intrauterine position, given the 2.4% likelihood that expulsion may
      have occurred at the time of subsequent visits, repeating the ultrasound (if
      available) should be considered for at least one (and possibly two) additional
      women's visit.

PMID- 22459235
TI  - Contraceptive choices of overweight and obese women in a publically funded
      hospital: possible clinical implications.
AB  - BACKGROUND: Despite the growing obesity epidemic in the United States, family
      planning for overweight and obese women has been understudied. The aim of this
      study was to describe the contraception methods selected by normal weight,
      overweight and obese women. STUDY DESIGN: We retrospectively reviewed 7262 charts
      of women who underwent first trimester surgical termination of pregnancy at the
      John H. Stroger, Jr. Hospital of Cook County between January 1, 2008, and January
      1, 2010. We analyzed the relationship between body mass index (BMI) and choice of
      contraceptive method, after adjusting for age, race, smoking and level of
      education. RESULTS: When compared to patients with BMI <25 kg/m2, overweight (BMI
      25-29.9 kg/m2) and obese patients (BMI >=30 kg/m2) were more likely to select the
      intrauterine device (OR 1.3, 95% CI 1.28-1.32 for overweight; OR 1.6, 95% CI 1.59
      1.61 for obese), contraceptive ring (OR 1.4, 95% CI 1.28-1.52 for overweight; OR
      1.6, 95% CI 1.57-1.63 for obese) and tubal ligation (OR 1.5 95% CI 1.44-1.62 for
      overweight; OR 2.9, 95% CI 2.79-3.01 for obese). They were less likely to choose
      injectable contraception (OR 0.7, 95% CI 0.59-0.81 for overweight; OR 0.52, 95%
      CI 0.48-0.56 for obese). There was no relationship between BMI and choice of
      condoms, oral contraceptive pills and implantable methods. CONCLUSION: In our
      population, the contraceptive choices of overweight and obese women differed from
      those of normal weight women. These differences in contraceptive selection are
      important to recognize in light of the potential effect of BMI on the safety and
      efficacy of different contraceptive methods. Further research is needed to
      evaluate the contraceptive preferences, risks and benefits for overweight and
      obese women.

PMID- 22459236
TI  - Resources and procedures in the treatment of heavy menstrual bleeding with the
      levonorgestrel-releasing intrauterine system (LNG-IUS) or hysterectomy in Brazil.
AB  - BACKGROUND: Heavy menstrual bleeding (HMB) is the most common complaint of women
      seeking gynecological care. Treatments included surgical or medical options
      including hysterectomy and the levonorgestrel-releasing intrauterine system (LNG
      IUS) due to the profound suppression of endometrial growth that intrauterine LNG
      exerts which results in amenorrhea or in a reduction of blood loss. OBJECTIVE:
      The study was conducted to evaluate the resources and procedures involved in
      inserting an LNG-IUS compared to performing hysterectomy in women with HMB in a
      public sector hospital in Brazil. STUDY DESIGN: Two cohorts of women were
      studied: women who accepted an LNG-IUS (n=124) and matched women who underwent
      hysterectomy on the same day (n=122). We evaluate the number of procedures
      carried out in each group of women, including those performed before the decision
      was made to insert an LNG-IUS or to perform hysterectomy, the insertion of the
      device itself and the surgical procedure, in addition to the procedures and
      complications registered up to 1 year after LNG-IUS insertion or hysterectomy.
      RESULTS: Age and the duration of HMB were significantly lower in the LNG-IUS
      acceptors than women at the hysterectomy group. The numbers of gynecological
      consultations and Pap smears were similar in both groups; however, women in the
      hysterectomy group also underwent laboratory tests, ultrasonography, chest X-ray
      and electrocardiogram. In the hysterectomy group, the main complications were
      hemorrhage (six), bladder/bowel perforation (four), complications with anesthesia
      (one), ureteral reimplantation required (one) and abdominal pain (two). At 1
      year, HMB was controlled in 83.1% of women in the LNG-IUS group, and 106 women
      continued with the device. CONCLUSIONS: Both treatments were effective in HMB
      control. Fewer resources and complications were observed in LNG-IUS acceptors
      when compared to hysterectomy. The LNG-IUS represents a good strategy for
      reducing the number of hysterectomies and the resources required for women with
      HMB.

PMID- 22459237
TI  - Prevalence of bacteria in the circulation of cardiovascular disease patients,
      Madurai, India.
AB  - Cardiovascular diseases (CVDs) have a complex aetiology determined by risk
      factors, which include genetic and environmental factors. Chronic infection and
      inflammation is reported to be a pathogenic determinant for the development of
      CVDs. Here, we report the prevalence of bacterial pathogens in the circulation of
      CVD patients in Madurai, India. Blood culturing was performed using BD BACTEC
      automated culture system and organisms were identified by16S rRNA gene sequence
      analysis. From a total of 133 samples screened, 47 samples showed culture
      positive which indicates a high level of bacteraemia in CVD patients. From the 47
      samples that showed growth, we have identified 57 bacterial isolates comprising
      35 different species. Coagulase negative Staphylococci (CoNS) was the most
      predominant group of bacteria and other notable bacterial species isolated in
      this study are discussed.

PMID- 22459238
TI  - Cardiac surgery and heparin induced thrombocytopaenia (HIT): a case report and
      short review.
AB  - This patient presented for emergency cardiac surgery following two episodes of
      thrombocytopaenia, one before and one associated with exposure to unfractionated
      heparin in a seven-week period of intensive care management. Although the
      diagnosis of heparin induced thrombocytopaenia (HIT) was uncertain on clinical
      grounds when assessed by current criteria, the positive antibody status directed
      management in accordance with the internationally recognised guidelines published
      by the American College of Chest Physicians (ACCP) Evidence-based Clinical
      Practice Guidelines. An alternative anticoagulant to unfractionated heparin was
      indicated for cardiopulmonary bypass. Bivalirudin was selected because of recent
      literature supporting its safe use.

PMID- 22459239
TI  - Inertial sensor-based feedback can reduce key risk metrics for anterior cruciate
      ligament injury during jump landings.
AB  - BACKGROUND: The incidence of anterior cruciate ligament (ACL) injury can be
      decreased through the use of intervention programs. However, the success of these
      programs is dependent on access to a skilled trainer who provides feedback; as
      such, these programs would benefit from a simple device with the capacity to
      provide high-quality feedback. HYPOTHESIS: Feedback based on kinematic
      measurements from a simple inertial sensor-based system can be used to modify key
      ACL injury risk metrics (knee flexion angle, trunk lean, knee abduction moment)
      during jump landing. STUDY DESIGN: Controlled laboratory study. METHODS:
      Seventeen subjects (7 male) were tested during drop jump tasks. Their movements
      were measured simultaneously with inertial, optoelectronic, and force platform
      systems. Feedback provided to the subjects was based only on measurements from
      the inertial sensor-based system (knee flexion angle, trunk lean, and thigh
      coronal velocity). The subjects conducted a baseline session (without landing
      instructions), then a training session (with immediate feedback), and finally an
      evaluation session (without feedback). The baseline and evaluation sessions were
      then tested for changes in the key risk metrics. RESULTS: The subjects increased
      their knee flexion angle (16.2 degrees ) and trunk lean (17.4 degrees ) after the
      training. They also altered their thigh coronal angular velocity by 29.4 deg/s
      and reduced their knee abduction moment by 0.5 %BW.Ht. There was a significant
      correlation (R (2) = 0.55) between the change in thigh coronal angular velocity
      and the change in knee abduction moment. CONCLUSION: Subjects reduced key risk
      metrics for ACL injury after training with the system, suggesting the potential
      benefit of instrumented feedback for interventional training. CLINICAL RELEVANCE:
      Interventional training for reducing the risk of ACL injury could be improved
      with a simple device that provides immediate feedback.

PMID- 22459240
TI  - Arthroscopic intra-articular disk excision of the sternoclavicular joint.

PMID- 22459241
TI  - Medial patellofemoral ligament reconstruction using semitendinosus tendons:
      polyester suture augmentation versus nonaugmentation.
AB  - BACKGROUND: The comparative clinical outcome of medial patellofemoral ligament
      reconstruction (MPFLR) using semitendinosus tendons with and without polyester
      suture augmentation for recurrent patellar instability is unknown. HYPOTHESIS:
      Medial patellofemoral ligament reconstruction with polyester suture augmentation
      will yield better results than MPFLR without augmentation for recurrent patellar
      instability in adults. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 2. METHODS: One hundred patients with recurrent patellar instability
      receiving MPFLR using semitendinosus tendons were randomly divided into 2 groups
      either with or without polyester suture augmentation. Tibial tubercle transfer
      was performed in most cases. Follow-ups were performed at 12, 24, and 60 months
      postoperatively, and computed tomography (CT) was performed immediately after the
      operation and at follow-up. The passive patellar glide test was performed before
      surgery, immediately after MPFLR during the operation, and at each follow-up
      point. The degree of knee function was evaluated preoperatively and at 2 and 5
      years postoperatively using the International Knee Documentation Committee,
      Lysholm, and Kujala rating scales. Redislocation or multiple episodes of patellar
      instability were considered failures. RESULTS: Forty-two patients in the
      augmentation group and 43 patients in the nonaugmentation group were followed for
      5 years and received complete serial CT examinations and functional evaluations.
      The correction of the static patellar position deteriorated over time in the
      nonaugmentation group but not in the augmentation group. The results of the
      passive patellar glide test indicated stable patellae in all patients immediately
      after MPFLR and more stable patellae in the augmentation group at each follow-up
      point. Functional evaluations at 2 and 5 years revealed statistically significant
      superior results in the augmentation group. Finally, no patient in the
      augmentation group and 2 (4.7%) in the nonaugmentation group experienced episodes
      of redislocation, and 1 patient (2.4%) in the augmentation group and 8 (18.6%) in
      the nonaugmentation group experienced multiple episodes of patellar instability,
      resulting in failure rates of 2.4% and 23.3% in the augmentation group and
      nonaugmentation group, respectively (P = .004). CONCLUSION: Medial patellofemoral
      ligament reconstruction with polyester suture augmentation results in better
      static patellar position, dynamic stability, and functional outcome than without
      augmentation in the treatment of recurrent patellar dislocation in adults.

PMID- 22459242
TI  - Association of ADIPOQ variants, total and high molecular weight adiponectin
      levels with coronary artery disease in diabetic and non-diabetic Brazilian
      subjects.
AB  - OBJECTIVE: To investigate the association of ADIPOQ variants, total and high
      molecular weight adiponectin (HMW) adiponectin levels with the prevalence of
      diabetes mellitus and coronary artery disease (CAD) diagnosed by coronary
      angiography in Brazilian subjects with high cardiovascular risk. METHODS: 603
      subjects undergoing coronary angiography were studied in regard to their glycemic
      status and presence of CAD (lesions >0%). We evaluated baseline concentrations of
      total and HMW adiponectin and three ADIPOQ variants: -11391G>A (rs17300539),
      +45T>G (rs2241766) and+276G>T (rs1501299). RESULTS: The G-allele of rs2241766 was
      associated with higher levels of total and HMW adiponectin, and the A-allele of
      rs17300539 was associated with higher levels of HMW adiponectin. Lower levels of
      total and HMW adiponectin were independently associated with CAD. The G-allele of
      rs2241766 (OR 2.45, 95% C.I. 1.05-6.04, p=0.04) and the G-allele of rs1501299 (OR
      1.89, 95% C.I. 1.04-3.45, p=0.03) were associated with CAD, and these
      associations were independent of circulating levels of adiponectin. CONCLUSIONS:
      In Brazilian subjects with high cardiovascular risk, CAD was associated with
      lower total and HMW adiponectin levels. The rs2241766 and rs1501299 polymorphisms
      were associated with CAD. The rs2241766 variant was associated with total and HMW
      adiponectin levels, while rs17300539 was associated with HMW adiponectin levels.

PMID- 22459243
TI  - Prevalence of gastroparesis-related symptoms in an unselected cohort of patients
      with Type 1 diabetes.
AB  - BACKGROUND: The prevalence of diabetic gastroparesis is not well defined because
      of discrepancy between objective measurements, i.e. gastric emptying time, and
      symptoms experienced by patients. Furthermore most studies have been performed on
      small selected cohorts. OBJECTIVE: To determine the prevalence of clinical
      symptoms of diabetic gastroparesis in a large unselected cohort of out-patients
      with Type 1 diabetes. METHODS: 1028 patients with Type 1 diabetes attending a
      specialized diabetes clinic were mailed a validated questionnaire; "patient
      assessment of upper gastrointestinal disorders-symptom severity index", in which
      a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis
      Cardinal Symptom Index). Response rate was 74.4% (n=765). All patients were
      classified according to presence or absence of late diabetic complications and
      clinical and paraclinical data were obtained. RESULTS: A GCSI Total Score >=1.90
      signified definite symptoms of gastroparesis (n=102) and patient charts were
      investigated for concomitant illness and/or medication influencing gastric
      emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%)
      patients with symptoms related to diabetic gastroparesis. Only 8 patients were
      previously diagnosed. HbA(1c) levels were significantly higher in patients with
      diabetic gastroparesis (8.4+/-1.3 vs. 8.2+/-1.2 respectively, p=0.02).
      Furthermore, patients with diabetic gastroparesis had more retinopathy (p=0.006)
      and peripheral polyneuropathy (16.7% vs. 6.7%, p<0.001) and there was a trend for
      diabetic nephropathy being more common (p=0.08). CONCLUSIONS: Symptoms of
      diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes
      in a specialized diabetes clinic and are associated with poor glycemic control
      and other late diabetic complications.

PMID- 22459244
TI  - Associations of plasma von Willebrand factor ristocetin cofactor activity and 5
      hydroxyindole acetic acid concentrations with blood flow in lower-leg arteries in
      Japanese type 2 diabetic patients with normal ankle-brachial index.
AB  - AIMS: To evaluate the associations of circulating levels of proinflammatory
      molecules and endothelial factors with blood flow in lower-leg arteries in
      diabetic patients with normal ankle-brachial index (ABI>0.9). METHODS: We
      enrolled 123 type 2 diabetic patients with normal ABI and 30 age-matched
      nondiabetic subjects consecutively admitted to our hospital. Flow volume and
      resistive index, an index of peripheral vascular resistance, at the popliteal
      artery were evaluated using gated two-dimensional cine-mode phase-contrast
      magnetic resonance imaging. An automatic device was used to measure ABI and
      brachial-ankle pulse-wave velocity (baPWV) for evaluation of arterial stiffness.
      Plasma soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte
      chemoattractant protein-1 (MCP-1) concentrations, serum high-sensitivity C
      reactive protein (hsCRP) levels, plasma von Willebrand factor ristocetin cofactor
      activity (VWF), and plasma vasoconstrictor serotonin metabolite 5-hydroxyindole
      acetic acid (5-HIAA) concentrations were measured. RESULTS: Diabetic patients had
      higher baPWV (P<.0001), resistive index (P<.0001), sICAM-1 (P<.0001), MCP-1
      (P=.0224), log hsCRP (P<.0001), VWF (P<.0001), 5-HIAA (P=.0015), and lower blood
      flow (P<.0001) than nondiabetic subjects. VWF (P=.0019) or 5-HIAA (P=.0011), but
      not sICAM-1, MCP-1, and log hsCRP, was negatively correlated with blood flow in
      diabetic patients. A multivariate analysis revealed that the significant
      independent determinants of blood flow were hypertension, use of renin
      angiotensin system inhibitors, VWF and 5-HIAA (r(2)=0.198, P<.0001) in diabetic
      patients. CONCLUSIONS: Plasma VWF and 5-HIAA concentrations are associated with
      blood flow and are involved in the pathogenesis of impaired peripheral
      circulation due to higher arterial stiffness and greater vascular resistance in
      lower-leg arteries in diabetic patients with normal ABI.

PMID- 22459245
TI  - First trimester maternal serum PIGF, free beta-hCG, PAPP-A, PP-13, uterine artery
      Doppler and maternal history for the prediction of preeclampsia.
AB  - OBJECTIVE: To evaluate the detection of pregnancy hypertensive disorders by
      integrating maternal history, serum biomarkers and uterine artery Doppler in the
      first trimester. METHODS: We prospectively recruited 2118 women that underwent an
      11-13 weeks aneuploidy screening. We gathered information on maternal history,
      uterine artery Doppler and serum biomarkers (PAPP-A, PlGF, PP-13 and free beta
      hCG). Models were developed for the prediction of overall preeclampsia (PE),
      early-onset PE, late-onset PE and gestational hypertension (GH). For each
      outcome, we performed a multivariate logistic regression starting from the
      saturated model: adopting a step-down procedure we excluded all factors not
      statistically significant (p > 0.05). Sensitivity models only for statistically
      significant parameters were calculated from the ROC curves for fixed false
      positive rates (FPR). RESULTS: Among 2118 women, 46 (2.17%) developed GH and 25
      (1.18%) were diagnosed with PE, including 12 (0.57%) early-onset PE and 13
      (0.61%) late-onset PE. For a fixed FPR of 10 and 5%, serum PlGF, free beta-hCG
      and chronic hypertension identified respectively 67 and 75% of women who
      developed early-onset PE. In the model for the prediction of overall PE the
      combination of the uterine artery Doppler pulsatility index (UtA PI) with PlGF
      and chronic hypertension reached a sensitivity of 60% for a 20% of FPR.
      CONCLUSION: An integration of maternal characteristics and first trimester
      maternal serum biomarkers (free beta-hCG and PlGF) provided a possible screening
      for early-onset PE. In the overall PE model, UtA PI turned out to be
      statistically significant but did not improve the detection rate.

PMID- 22459247
TI  - Are humans increasing bacterial evolvability?
AB  - Attempts to control bacterial pathogens have led to an increase in antibiotic
      resistant cells and the genetic elements that confer resistance phenotypes. These
      cells and genes are disseminated simultaneously with the original selective
      agents via human waste streams. This might lead to a second, unintended
      consequence of antimicrobial therapy; an increase in the evolvability of all
      bacterial cells. The genetic variation upon which natural selection acts is a
      consequence of mutation, recombination and lateral gene transfer (LGT). These
      processes are under selection, balancing genomic integrity against the advantages
      accrued by genetic innovation. Saturation of the environment with selective
      agents might cause directional selection for higher rates of mutation,
      recombination and LGT, producing unpredictable consequences for humans and the
      biosphere.

PMID- 22459246
TI  - Environmental proteomics, biodiversity statistics and food-web structure.
AB  - Pioneering studies in environmental proteomics have revealed links between
      protein diversity and ecological function in simple ecological communities, such
      as microbial biofilms. In the near future, high-throughput proteomic methods will
      be applied to more complex ecological systems in which microbes and macrobes
      interact. Data structures in biodiversity and protein surveys have many
      similarities, so the statistical methods that ecologists use for analyzing
      biodiversity data should be adapted for use with quantitative surveys of protein
      diversity. However, increasing quantities of protein and bioinformatics data will
      not, by themselves, reveal the functional significance of proteins. Instead,
      ecologists should be measuring changes in the abundance of protein cohorts in
      response to replicated field manipulations, including nutrient enrichment and
      removal of top predators.

PMID- 22459248
TI  - [Spanish multicentre study for the prevention of medication errors: results over
      four years (2007-2011)].
AB  - OBJECTIVE: The primary objective of the Spanish Multicentre Study for the
      Prevention of Medication Errors 2007-2011 was to increase patient safety by
      improving drug practices in 26 participating Spanish hospitals. The secondary
      objective was to ascertain the medication error rate. METHOD: We used a modified
      Barker and McConnell observation method. RESULTS: During 2007-2008, 21 009
      observations were recorded In 23 hospitals; during 2008-2009, 11 320 observations
      were recorded in 10 hospitals; during 2009-2010, 6819 observations were recorded
      in 8 hospitals, and during 2010-2011, 5876 observations were recorded in six
      hospitals. Error rates, including medication time errors and failure to inform
      patients came to 21.7%, 33.3%, 35.6% and 25.7% in each of the years respectively.
      Excluding time errors, the rates were 18.2%, 32.2%, 33.4% and 23.5%; excluding
      failure to inform patients as well, rates dropped to 12.6%, 14.8%, 12.8% and
      8.6%. STRATEGIES FOR IMPROVEMENT: a normalised drug administration timetable,
      normalised IV drug dilutions and rates, better drug administration coordination
      with mealtimes, electronic prescription, improved patient identification
      measures, adjusting doses for kidney function, drug reconciliation programmes and
      patient and drug bar code scanning. CONCLUSIONS: 1. The applied measures improved
      patient safety through better drug practices in participating EMOPEM hospitals.
      2. Drug error rates obtained for this sample of Spanish hospitals are some of the
      highest published. They are significantly lower, however, when we exclude time
      errors and failure to inform the patient.

PMID- 22459249
TI  - Profiles of toxic and non-toxic oligopeptides of Radiocystis fernandoii
      (Cyanobacteria) exposed to three different light intensities.
AB  - Cyanobacteria produce a high variety of bioactive oligopeptides, which function,
      ecological, physiological roles and responses to environmental changes are still
      unclear. The influence of light intensity on the cell quota and the diversity of
      oligopeptides of two strains of the cyanobacterium Radiocystis fernandoii were
      experimentally tested. The peptides were quantified by HPLC and identified by a
      MALDI-TOF-TOF. Microcystins (MC) were generally more abundant in the treatment
      with low light. A compensatory mechanism was observed for the different variants
      of microcystin, whereby MC-RR responses were contrary to those observed for the
      other three variants and showed higher concentration in the treatment with
      intermediate light. Two microviridins were also produced at higher amounts at
      intermediate irradiance. For cyanopeptolins and a third microviridin no
      significant difference among treatments was found. The absence of a similar
      response for all peptides suggests that these compounds may have unique cellular
      functions, which better understanding could help explaining changes in toxicity.
      Finally, we observed that each chemical profile reflected in physiological
      differences between strains, strengthening the idea that chemotypes may act as
      distinct ecotypes in nature.

PMID- 22459250
TI  - Exploring the environmental transmission electron microscope.
AB  - The increasing interest and development in the field of in situ techniques have
      now reached a level where the idea of performing measurements under near
      realistic conditions has become feasible for transmission electron microscopy
      (TEM) while maintaining high spatial resolution. In this paper, some of the
      opportunities that the environmental TEM (ETEM) offers when combined with other
      in situ techniques will be explored, directly in the microscope, by combining
      electron-based and photon-based techniques and phenomena. In addition,
      application of adjacent setups using sophisticated transfer methods for
      transferring the specimen between specialized in situ equipment without
      compromising the concept of in situ measurements will be exploited. The
      opportunities and techniques are illustrated by studies of materials systems of
      Au/MgO and Cu(2)O in different gaseous environments.

PMID- 22459251
TI  - Direct observation of ferroelectric domain switching in varying electric field
      regimes using in situ TEM.
AB  - In situ Transmission Electron Microscopy (TEM) techniques can potentially fill in
      gaps in the current understanding interfacial phenomena in complex oxides. Select
      multiferroic oxide materials, such as BiFeO(3) (BFO), exhibit ferroelectric and
      magnetic order, and the two order parameters are coupled through a quantum
      mechanical exchange interaction. The magneto-electric coupling in BFO allows
      control of the ferroelectric and magnetic domain structures via applied electric
      fields. Because of these unique properties, BFO and other magneto-electric
      multiferroics constitute a promising class of materials for incorporation into
      devices such as high-density ferroelectric and magnetoresistive memories, spin
      valves, and magnetic field sensors. The magneto-electric coupling in BFO is
      mediated by volatile ferroelastically switched domains that make it difficult to
      incorporate this material into devices. To facilitate device integration, an
      understanding of the microstructural factors that affect ferroelastic relaxation
      and ferroelectric domain switching must be developed. In this article, a method
      of viewing ferroelectric (and ferroelastic) domain dynamics using in situ biasing
      in TEM is presented. The evolution of ferroelastically switched ferroelectric
      domains in BFO thin films during many switching cycles is investigated. Evidence
      of partial domain nucleation, propagation, and switching even at applied electric
      fields below the estimated coercive field is revealed. Our observations indicate
      that the occurrence of ferroelastic relaxation in switched domains and the
      stability of these domains is influenced the applied field as well as the BFO
      microstructure. These biasing experiments provide a real time view of the complex
      dynamics of domain switching and complement scanning probe techniques.
      Quantitative information about domain switching under bias in ferroelectric and
      multiferroic materials can be extracted from in situ TEM to provide a predictive
      tool for future device development.

PMID- 22459252
TI  - Effects of heat treatment on evolution of microstructure of boron free and boron
      containing biomedical Ti-13Zr-13Nb alloys.
AB  - In the present study, the effects of heat treatment on the microstructure of Ti
      13Zr-13Nb (TZN) and Ti-13Zr-13Nb-0.5B (TZNB) alloys have been investigated.
      Depending on the heat treatment conditions, the microstructure of the heat
      treated TZN alloy consisted mainly of elongated and/or equiaxed alpha, beta or
      martensite. Slow cooling (furnace or air cooling) from the solution treatment
      temperature produced alpha and beta phases in the microstructure. Rapid cooling
      (water quenching) resulted in martensite and retained beta when the solution
      treatment temperature was above or close to beta transus. However, martensite was
      not formed after water quenching from a solution treatment temperature which was
      below beta transus due to partitioning effect of the alloying elements.
      Increasing the cooling rate from the furnace cooling to the air cooling led to
      finer microstructure. Aging of water quenched samples transformed the martensite,
      if present, into alpha and beta, and the morphology of alpha phase changed from
      elongated to equiaxed and enhanced the growth of alpha. The microstructure of all
      the TZNB samples consisted of dispersed precipitated particles of TiB in the
      matrix. The majority of the boride particles showed an acicular (needle like)
      morphology. The other phases present in the TZNB alloy were similar to those in
      the similarly heat treated TZN alloy. Moreover, a growth of alpha phase was
      observed in the microstructure of TZNB alloy when compared with that of TZN
      alloy.

PMID- 22459253
TI  - Attention and executive functions profile in childhood absence epilepsy.
AB  - Childhood absence epilepsy (CAE) has been associated with executive functions and
      attention deficits. To clarify the issue of neurocognitive impairments in CAE, we
      investigated whether specific executive functions and attention deficit patterns
      were present in a well-defined group of children with CAE who were taking
      valproic acid. Participants included 15 children with CAE and 15 healthy controls
      aged 8-15 years and matched for sex, age and IQ. We compared the performances of
      the two groups in the following neuropsychological domains: planning and problem
      solving (TOL), verbal fluency (FAS and CAT), verbal short-term memory (DSF),
      verbal working memory (DSB), visuospatial memory (Corsi Block Tapping Test) and
      sustained and divided attention (TMT-A and TMT-B). No differences were found
      between the two groups on measures of intellectual functioning, verbal short-term
      memory and visuospatial memory. By contrast, significant differences were found
      in total time of planning task, phonological and category fluency and sustained
      and divided attention. Future studies that systematically examine different
      aspects of attention and executive functions are needed to outline a clear and
      specific neuropsychological profile in CAE.

PMID- 22459254
TI  - EEG characteristics and visual cognitive function of children with attention
      deficit hyperactivity disorder (ADHD).
AB  - Using visual and auditory continuous performance tests (CPT) and EEG, cognitive
      function and EEG power were investigated in patients with attention deficit
      hyperactivity disorder (ADHD). CPT and EEG were conducted for 44 ADHD children
      and 44 healthy controls of comparable age and sex. The EEG power tests include
      relative power of theta, alpha, and beta, and theta/beta and theta/alpha ratios.
      ADHD patients showed significantly higher theta relative power, lower beta
      relative power, and higher theta/beta ratio (p<0.05). ADHD patients showed a
      significantly lower score of auditory CPT (p<0.05). The EEG power characteristics
      were correlated significantly with the visual attention function in ADHD children
      (p<0.01). Higher-order level cognitive dysfunction affects ADHD pathogenesis.
      Cortical hypoarousal effects on several mechanisms including the fronto-striatal
      circuitry may be implicated in the inhibition of prepotent and premature
      responses.

PMID- 22459255
TI  - Successful retrieval of a broken intravascular ultrasound catheter tip from a
      coronary artery.
AB  - The fracture of IVUS catheter tip in the coronary artery is a very rare
      complication. It should be removed as soon as possible. Although it seems to be
      easy at first glance, percutaneous retrieval of broken IVUS catheter tip has some
      challenges. We hereby present a case report of successful percutaneous retrieval
      of broken IVUS catheter, probably caused by calcific left main stenosis, from the
      left circumflex artery using loop snare technique.

PMID- 22459256
TI  - Successful percutaneous revascularization of totally occluded left subclavian
      artery using orbital atherectomy.
AB  - Subclavian artery steal (SAS) after coronary artery bypass graft (CABG) has been
      reported to be as high as 3.4%. These patients with patent left internal mammary
      artery (LIMA) anastomosis will also have coronary-subclavian steal syndrome
      (CSSS). Percutaneous intervention (PCI) by balloon angioplasty (BA) and stenting
      has been done successfully for subclavian artery (SA) stenosis. The visibility of
      the vertebral artery (VA) and LIMA during BA and stent positioning is extremely
      important. Debulking total occlusions by orbital atherectomy (OA) and avoiding
      unnecessary BA, stenting across side branches may decrease the chance of plaque
      shifting and subsequent loss of flow especially if they have ostial disease.
      Herein we report successful OA, BA and stenting of chronic total occlusion (CTO)
      of proximal left subclavian artery in a patient with coronary-subclavian steal
      syndrome with preservation of LIMA and diseased left vertebral artery (VA).

PMID- 22459257
TI  - Malignant fungating wounds: the meaning of living in an unbounded body.
AB  - BACKGROUND: Malignant fungating wounds may have significant physiological,
      psychological and emotional consequences on patients and their families. This
      study focuses on understanding the lived experiences of patients with a malignant
      fungating breast wound and their informal carers. METHOD: The methodological
      framework of interpretative phenomenological approach according to Heidegger was
      used. Nine patients were interviewed from January until November 2009. RESULTS:
      The results demonstrate that most of the patients and their informal carers were
      on their own while struggling with the erosion of their physical boundaries. The
      women report a lack of information and advice about how to manage the wound as
      well as the physical and social limitations imposed on them because of copious
      wound exudate, odour and bleeding. The women used many different methods and
      approaches to maintain the boundedness of the body. CONCLUSION: This study
      contributes to understanding that losing control over the body meant for the
      women losing control over themselves and their lives. The unboundedness was
      demonstrated through the symptom experiences. Therefore the care of women needs
      strategies that are integrated in a palliative, holistic, empathic approach. In
      particular skills for palliative wound care among medical and nursing staff need
      to be developed as the women and their carers report a lack of information and
      advice about how to manage the wound as well as the physical limitations and
      psychosocial consequences of struggling to maintain the boundedness of the body.

PMID- 22459258
TI  - Barriers to breast cancer screening participation among Jordanian and Palestinian
      American women.
AB  - PURPOSE: Increasing breast cancer screening (BCS) among diverse women from
      minority groups is a goal of health care providers and national organizations as
      a way to help in the early detection and treatment of breast cancer. The purpose
      of this article is to investigate barriers to BCS encountered by Jordanian and
      Palestinian women living in the United States (US). METHODS: Descriptive content
      analysis of interviews of 107 Jordanian and Palestinian immigrant women provided
      data on BCS barriers that were thematically analyzed. RESULTS: Data revealed 4
      barriers that affect Jordanian and Palestinian immigrant women's participation in
      BCS: (1) culture-specific barriers such as embarrassment, family relationships,
      fatalism, and traditional healers consultation; (2) immigration-related barriers
      (citizenship issues and language); (3) general barriers (including
      nonparticipation in health screening, stigmatization of cancer, fear, and
      ignorance about BCS); and (4) irrelevant barriers. CONCLUSIONS: Clinicians should
      be cognizant of the culture, beliefs and practices of Arab Middle Eastern
      immigrant women and the influence of these factors on their decision to
      participate in routine BCS. To increase participation in BCS and knowledge of
      breast cancer, appropriate language and culturally sensitive educational
      materials should be created and made available to Arab Middle Eastern immigrant
      women.

PMID- 22459259
TI  - A comparative descriptive study examining the perceptions of cancer patients,
      family caregivers, and nurses on patient symptom severity in Turkey.
AB  - PURPOSE: Perform a comparative descriptive study that aims to describe the
      symptom severity of patients receiving chemotherapy and to compare patient self
      reports of symptom severity with inferences made by nurses and family caregivers.
      METHODS AND SAMPLE: The study was performed in the chemotherapy unit of a
      university hospital. The study was conducted on 119 patients undergoing
      chemotherapy that had a family caregiver and a nurse (n = 7) primarily
      responsible for their care. Symptom assessments were completed using the Edmonton
      Symptom Assessment System (ESAS). Symptoms were rated independently by the
      patient, caregiver and nurse. RESULTS: The patients reported severe tiredness,
      loss of well-being, anxiety, drowsiness, appetite changes, depression, pain and
      nausea. The patients and caregivers showed a strong agreement of the patients'
      symptoms (P < .001). Patients and nurses showed poor to fair agreement of the
      symptoms of pain, tiredness, nausea, depression, drowsiness, appetite, loss of
      well-being, skin and nail changes, mouth sores, and hand numbness (P < .05). The
      patients' mean scores of symptoms such as pain, depression, anxiety, drowsiness
      and loss of well-being were lower than those of the caregivers. The patients'
      mean scores of symptoms such as tiredness, shortness of breath, skin and nail
      changes and mouth sores were higher than scores of nurses (P < .05). CONCLUSION:
      Perceptions of formal or informal caregivers about symptoms in patients with
      cancer will help clinicians to develop strategies or approaches to improve the
      caregiver symptom assessment.

PMID- 22459260
TI  - Supporting self-management of pain in cancer patients: methods and lessons
      learned from a randomized controlled pilot study.
AB  - PURPOSE OF THE RESEARCH: The purposes of this paper are to describe the methods
      used and the knowledge gained during a pilot study that evaluated the effects of
      a self-management intervention for cancer pain, as well as the adaptations that
      were made for a larger clinical trial. METHODS AND SAMPLE: In a randomized
      controlled trial, the adapted German version of the PRO-SELF((c)) Plus Pain
      Control Program (PCP), a 10-week intervention to support self-management of pain
      in adult oncology outpatients and their family caregivers, was compared to
      attention control. Primary endpoints were average and worst pain measured at 6,
      10, 14, and 22 weeks after enrollment. KEY RESULTS: A total of 39 patients (19
      intervention, 20 control) were recruited over 18 months. During the study,
      inclusion criteria were expanded. Furthermore, the structured timing of the
      intervention visits was too static for a dynamic symptom like cancer pain. The
      intervention was expanded to include symptoms that severely impacted pain self
      management including chemotherapy-induced nausea and vomiting. CONCLUSIONS: Apart
      from the provision of information and skills building, coaching cancer patients
      across a complex treatment is an important function of an intervention to support
      pain self-management. The pilot study proved to be highly useful in order to
      adapt planned study procedures, to balance burden and benefit for participants,
      and to customize the intervention to patients' needs and abilities in order to
      enhance feasibility and effectiveness. Findings from this pilot study will be
      fully integrated in a larger randomized controlled trial. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00920504.

PMID- 22459261
TI  - Direct determination of actin polarity in the cell.
AB  - Actin filaments are polar structures that exhibit a fast growing plus end and a
      slow growing minus end. According to their organization in cells, in parallel or
      antiparallel arrays, they can serve, respectively, in protrusions or in
      contractions. The determination of actin filament polarity in subcellular
      compartments is therefore required to establish their local function. Myosin
      binding has previously been the sole method of polarity determination. Here, we
      report the first direct determination of actin filament polarity in the cell
      without myosin binding. Negatively stained cytoskeletons of lamellipodia were
      analyzed by adapting electron tomography and a single particle analysis for
      filamentous complexes. The results of the stained cytoskeletons confirmed that
      all actin filament ends facing the cell membrane were the barbed ends. In
      general, this approach should be applicable to the analysis of actin polarity in
      tomograms of the actin cytoskeleton.

PMID- 22459262
TI  - Functional role of the sarcin-ricin loop of the 23S rRNA in the elongation cycle
      of protein synthesis.
AB  - The sarcin-ricin loop (SRL) is one of the longest conserved sequences in the 23S
      ribosomal RNA. The SRL has been accepted as crucial for the activity of the
      ribosome because it is targeted by cytotoxins such as alpha-sarcin and ricin that
      completely abolish translation. Nevertheless, the precise functional role of the
      SRL in translation is not known. Recent biochemical and structural studies
      indicate that the SRL is critical for triggering GTP hydrolysis on elongation
      factor Tu (EF-Tu) and elongation factor G (EF-G). To determine the functional
      role of the SRL in the elongation stage of protein synthesis, we analyzed
      mutations in the SRL that are known to abolish protein synthesis and are lethal
      to cells. Here, we show that the SRL is not critical for GTP hydrolysis on EF-Tu
      and EF-G. The SRL also is not essential for peptide bond formation. Our results,
      instead, suggest that the SRL is crucial for anchoring EF-G on the ribosome
      during mRNA-tRNA translocation.

PMID- 22459263
TI  - Elongation kinetics of polyglutamine peptide fibrils: a quartz crystal
      microbalance with dissipation study.
AB  - Abnormally expanded polyglutamine domains in proteins are associated with several
      neurodegenerative diseases, including Huntington's disease. Expansion of the
      polyglutamine (polyQ) domain facilitates aggregation of the affected protein, and
      several studies directly link aggregation to neurotoxicity. Studies of synthetic
      polyQ peptides have contributed substantially to our understanding of the
      mechanism of aggregation. In this report, polyQ fibrils were immobilized onto a
      sensor, and their elongation by polyQ peptides of various length and conformation
      was examined using quartz crystal microbalance with dissipation monitoring (QCM
      D). The rate of elongation increased as the peptide length increased from 8 to 24
      glutamines (Q8, Q20, and Q24). Monomer conformation affected elongation rates:
      insertion of a beta-turn template d-Pro-Gly in the center of the peptide
      increased elongation rates several-fold, while insertion of Pro-Pro dramatically
      slowed elongation. Dissipation measurements of the QCM-D provided qualitative
      information about mechanical properties of the elongating fibrils. These data
      showed clear differences in the characteristics of the elongating aggregates,
      depending on the specific identity of the associating polyQ peptide. Elongation
      rates were sensitive to the pH and ionic strength of the buffer. Comparison of
      QCM-D data with those obtained by optical waveguide lightmode spectroscopy
      revealed that very little water was associated with the elongation of fibrils by
      the peptide containing d-Pro-Gly, but a significant amount of water was
      associated when the fibrils were elongated by Q20. Together, the data indicate
      that elongation of polyQ fibrils can occur without full consolidation to the
      fibril structure, resulting in variations to the aggregate structure during
      elongation.

PMID- 22459264
TI  - Ginkgo biloba extract EGb 761(r) in dementia with neuropsychiatric features: a
      randomised, placebo-controlled trial to confirm the efficacy and safety of a
      daily dose of 240 mg.
AB  - A multi-centre, double-blind, randomised, placebo-controlled, 24-week trial with
      410 outpatients was conducted to demonstrate efficacy and safety of a 240 mg once
      daily formulation of Ginkgo biloba extract EGb 761((r)) in patients with mild to
      moderate dementia (Alzheimer's disease or vascular dementia) associated with
      neuropsychiatric symptoms. Patients scored 9 to 23 on the SKT cognitive battery,
      at least 6 on the Neuropsychiatric Inventory (NPI), with at least one of four key
      items rated at least 4. Primary outcomes were the changes from baseline to week
      24 in the SKT and NPI total scores. The ADCS Clinical Global Impression of Change
      (ADCS-CGIC), Verbal Fluency Test, Activities of Daily Living International Scale
      (ADL-IS), DEMQOL-Proxy quality-of-life scale and 11-point box scales for tinnitus
      and dizziness were secondary outcome measures. Patients treated with EGb 761((r))
      (n = 200) improved by 2.2 +/- 3.5 points (mean +/- sd) on the SKT total score,
      whereas those receiving placebo (n = 202) changed only slightly by 0.3 +/- 3.7
      points. The NPI composite score improved by 4.6 +/- 7.1 in the EGb 761((r))
      treated group and by 2.1 +/- 6.5 in the placebo group. Both drug-placebo
      comparisons were significant at p < 0.001. Patients treated with EGb 761((r))
      also showed a more favourable course in most of the secondary efficacy variables.
      In conclusion, treatment with EGb 761((r)) at a once-daily dose of 240 mg was
      safe and resulted in a significant and clinically relevant improvement in
      cognition, psychopathology, functional measures and quality of life of patients
      and caregivers.

PMID- 22459265
TI  - Strangulated paraumbilical hernia-An unusual complication of a Meckel's
      diverticulum.
AB  - INTRODUCTION: Meckel's diverticulum is the commonest congenital abnormality of
      the gastrointestinal tract. Most are asymptomatic but can rarely present with
      varies forms of intestinal obstruction. PRESENTATION OF CASE: We present an
      unusual case of an elderly African woman with a massive strangulated
      paraumbilical hernia as a complication from a Meckel's diverticulum. DISCUSSION:
      Meckel's diverticulum presenting as a strangulated paraumbilical hernia is
      uncommon and can be difficult to diagnose. It is often only found
      intraoperatively. Delay in referral due to poor access can potentially lead to
      adverse outcome. CONCLUSION: Although uncommon, a through clinical assessment is
      of paramount importance and timely operative intervention must occur in order to
      provide the best outcome for these patients.

PMID- 22459266
TI  - Glenohumeral joint penetration with a 21-gauge standard needle.
AB  - BACKGROUND: This study assessed whether a standard 21-gauge needle (length, 38.1
      mm [1.5 inches]) is more likely to penetrate the glenohumeral joint through an
      anterior or a posterior approach. METHODS: Seventy-nine patients underwent an
      arthroscopic procedure on the glenohumeral joint. The depth from the skin to the
      joint capsule was compared between the posterior approach (10 mm medial and
      inferior to the posterolateral tip of the acromion) and the anterior approach
      (direct visualization through the rotator interval). Each approach was measured
      twice and the mean used. The data were analyzed using a 2-sided paired t test.
      RESULTS: The anterior approach was shorter than the posterior approach in all
      patients (P < .001). This was less than the length of a standard needle in 98.7%
      of patients. The mean skin-to-joint capsule depth was 43.5 mm (range, 24-58 mm)
      with the posterior approach and 27.1 mm (range, 12.5-40 mm) with the anterior
      approach. On average, the posterior approach was 16.3 mm deeper (range, 0.5-31.5
      mm) than the anterior approach. CONCLUSIONS: Injections through the anterior
      approach are more likely to penetrate the glenohumeral joint than through the
      posterior approach if a standard needle is used.

PMID- 22459267
TI  - Changes in aphid probing behaviour as a function of insect age and plant
      resistance level.
AB  - Aphids perform a series of behaviours to assess feeding suitability and, hence,
      to select a plant. Little information, however, is available on such behaviour
      after aphids have settled on a plant. Observation of probing behaviour over an
      extended period of time can improve our understanding of insect-plant
      interactions and is instrumental in the study of crop resistance. Here, we
      assessed the influence of aphid age and plant resistance level on aphid
      behaviour. An electrical penetration graph (EPG) technique was implemented to
      monitor the behaviour of potato aphid, Macrosiphum euphorbiae, alates on potato,
      Solanum tuberosum, and on both a susceptible and a resistant genotype of a wild
      Solanum species, S. chomatophilum. The behaviour was measured at daily intervals
      for the first seven days following adult emergence. The results indicated
      independent and interacting effects of aphid age and plant genotype on probing
      behaviour. Some behavioural discrepancies between susceptible and resistant
      genotypes were only observed after the first day, thus highlighting the limits of
      punctual one-day behavioural studies to assess plant resistance mechanisms. Our
      work supports the hypothesis that aphids continuously adapt their behaviour to
      the plant characteristics. 

PMID- 22459268
TI  - Response to "Ipilimumab (Yervoy) and the TGN1412 catastrophe".

PMID- 22459269
TI  - A defect of CD16-positive monocytes can occur without disease.
AB  - The CD16-positive monocytes have been first described in 1988 but to date no
      selective defect in the number of these cells in blood has been reported. We now
      describe a family in which three of four siblings lack both CD16-positive
      monocyte subsets, i.e. the nonclassical and the intermediate monocytes. All three
      had CD16-positive monocytes of 2 cells/MUl or less as compared to 52+/-18
      cells/MUl in healthy controls. The index case was affected by recurrent pleural
      effusion and infections and had evidence of an auto-inflammatory condition but no
      mutation of any of the relevant candidate genes. The other two siblings without
      CD16-positive monocytes were apparently healthy. There was no defect in serum M
      CSF levels and no mutation in the M-CSF and M-CSFR genes. The data indicate that
      the absence of CD16-positive monocytes in blood does not lead to disease.

PMID- 22459270
TI  - Functional analysis of mouse ficolin-B and detection in neutrophils.
AB  - Ficolins and mannan-binding lectin recognize pathogen-associated molecular
      patterns and initiate the lectin pathway of complement activation via the
      associated serine proteases. In contrast to human ficolins and mouse ficolin-A,
      mouse ficolin-B has been considered incapable of complement activation. Dose
      dependent binding of recombinant ficolin-B to immobilized GlcNAc, acetylated BSA,
      acetylated LDL, and fetuin was detected with ficolin-B-specific monoclonal
      antibodies. Recombinant ficolin-B bound to immobilized acetylated bovine serum
      albumin interacted with recombinant human mannan-binding lectin-associated serine
      protease-2, which led to C4 cleavage, thus demonstrating the capability of
      ficolin-B to activate the lectin pathway. Ficolin-B-specific monoclonal
      antibodies identified natural ficolin-B protein in lysates of mouse granulocytes
      isolated from the bone marrow. These results identify mouse ficolin-B as a
      functional member of the ficolin family activating complement via the lectin
      pathway.

PMID- 22459271
TI  - Deciphering the molecular bases of the biological effects of antibodies against
      Interleukin-2: a versatile platform for fine epitope mapping.
AB  - Elucidating the network of interactions established by Interleukin-2 is a key
      step to understanding its role as a master regulator of the immune system.
      Binding of this cytokine by specific antibodies gives rise to different classes
      of immune complexes that boost or inhibit immune responses. The molecular bases
      of such functional dichotomy are likely related to the nature of the recognized
      epitopes, making it necessary to perform fine epitope mapping studies. The
      current work was aimed at developing a versatile platform to do so. This was
      accomplished by display of human and mouse Interleukin-2 on filamentous phages,
      together with extensive mutagenesis of both antigens and high throughput
      screening of binding properties of more than 200 variants. Detailed molecular
      pictures of the epitopes were thus delineated for four antibodies against either
      human or mouse Interleukin-2, which refined and, in some cases, modified the
      conclusions derived from previous mapping studies with peptide libraries.
      Overlapping surface patches on mouse Interleukin-2 that also coincide with the
      predicted interface between the cytokine and its receptor alpha chain were shown
      to be recognized by two monoclonal antibodies that promote enhancement of immune
      responses, shedding new light on the structural bases of their biological
      activity. Our strategy was powerful enough to reveal multiple binding details and
      could be used to map the epitopes recognized by other antibodies and to explore
      additional interactions involving Interleukin-2 and related cytokines, thus
      contributing to our understanding of the complex structure-function relationships
      within the immune system.

PMID- 22459272
TI  - An MBL-like protein may interfere with the activation of the proPO-system, an
      important innate immune reaction in invertebrates.
AB  - An important characteristic of the innate immune systems of crayfish and other
      arthropods is the activation of a serine proteinase cascade in the hemolymph,
      which results in the activation of prophenoloxidase and subsequently leading to
      the formation of toxic quinones and melanin. Although no true complement
      homologues have been detected in crayfish or crustaceans, several proteins with
      similarities to vertebrate pattern recognition receptors (PRRs), which are
      involved in the lectin pathway of complement activation in vertebrates, are
      present. One is a C-type lectin, a mannose-binding lectin (Pl-MBL), which is
      secreted from granular hemocytes. Here we report that Pl-MBL has LPS-binding
      capacity and is dependent upon high Ca(2+) for its solubility and Pl-MBL
      interferes with proPO activation in vitro when HLS is prepared at high Ca(2+).
      The proPO-activating system is efficiently activated by microbial polysaccharides
      and it has to be neatly regulated to avoid activation in places where it is
      inappropriate and the active enzyme PO should be prevented from spreading
      throughout the body of the animal. This may be particularly important during
      molting when proPO is involved in hardening of a new cuticle and the animal is
      vulnerable to microbes. The presence of high amount of Pl-MBL in the granular
      hemocytes may play a role in this process. Since a hemocyte lysate supernatant
      (HLS) prepared at 100 mM Ca(2+) could become activated when the concentration of
      LPS was increased up to 3 mg/ml, this may indicate that Pl-MBL acts as a
      scavenger for LPS to prevent spreading of LPS in the hemolymph to avoid further
      activation of the proPO-system.

PMID- 22459273
TI  - Robust adaptive learning of feedforward neural networks via LMI optimizations.
AB  - Feedforward neural networks (FNNs) have been extensively applied to various areas
      such as control, system identification, function approximation, pattern
      recognition etc. A novel robust control approach to the learning problems of FNNs
      is further investigated in this study in order to develop efficient learning
      algorithms which can be implemented with optimal parameter settings and
      considering noise effect in the data. To this aim, the learning problem of a FNN
      is cast into a robust output feedback control problem of a discrete time-varying
      linear dynamic system. New robust learning algorithms with adaptive learning rate
      are therefore developed, using linear matrix inequality (LMI) techniques to find
      the appropriate learning rates and to guarantee the fast and robust convergence.
      Theoretical analysis and examples are given to illustrate the theoretical
      results.

PMID- 22459275
TI  - FKBP5 polymorphisms as vulnerability to anxiety and depression in patients with
      advanced gastric cancer: a controlled and prospective study.
AB  - Cancer patients, who have to adapt to a long treatment process with multiple
      stressful events, show various stress responses. Genetic components may
      contribute to individual differences in stress response and risk for development
      of stress-related psychiatric problems. The present study aimed to investigate
      the influence of FK506 binding protein 5 (FKBP5) gene polymorphisms regulating
      the hypothalamic-pituitary-adrenal (HPA) axis on individual distress levels in
      cancer patients faced with similar stressful situation. The present study used a
      prospective design to elucidate predictors of distress. A total of 130 patients
      (90 males, 40 females) who were newly diagnosed with advanced gastric cancer and
      supposed to receive first-line chemotherapy were initially assessed, and a six
      week follow-up assessment occurred for 93 patients (63 males, 30 females) after
      two cycles of chemotherapy. Distress levels and coping patterns were measured by
      the Hospital Anxiety and Depression Scale (HADS) and Mini-Mental Adjustment to
      Cancer (Mini-MAC) scale. For genetic factors, three single nucleotide
      polymorphisms of FKBP5 rs1360780, rs9296158 and rs9470080 were genotyped. For
      HADS-anxiety, FKBP5 rs9296158 had a significant group-by-time interaction
      (p=0.015), and rs9470080 and rs1360780 had a marginally significant interaction
      (p=0.023, p=0.038, respectively). For HADS-depression, rs9470080 and rs9296158
      had a marginally significant group-by-time interaction (p=0.026, p=0.032,
      respectively). In addition, a step-wise linear regression analysis showed that
      FKBP5 rs9470080 and rs9296158 were significant predictors of anxiety and
      depression after prolonged stress exposure in cancer patients. Our findings
      indicate that the genetic factors regulating the HPA axis such as FKBP5 gene
      polymorphisms may play a crucial role in anxiety and depression following
      prolonged stress exposure.

PMID- 22459276
TI  - [Health and Immigration: creating a catalogue of resources to improve
      communication].

PMID- 22459277
TI  - [Patient safety risks in Primary Health Care: identification and prevention of
      adverse events].
AB  - OBJECTIVE: To determine whether there are pro-active strategies for identifying
      risks to patient safety, the potential risks identified by the professionals, and
      the solutions to prevent their occurrence. MATERIALS AND METHODS: A descriptive
      retrospective study was conducted on Primary Health Care units in the process of
      accreditation. This work was performed at the Andalusian Agency for Health Care
      Quality through the analysis of primary healthcare units assessed. A total of 61
      Primary healthcare units were assessed between June 2010 to June 2011. The main
      measurements were methods for identifying and prioritising risks, prioritised
      risks, and solutions provided by the Primary Health Care units. The risks and
      solutions were classified into 8 categories (medication, infection, diagnosis,
      management, patient accidents, communication, care, medical devices/equipment).
      The data were obtained in our computer application for the accreditation process
      (Me_joraC). RESULTS: Just under half (47.5%) of the healthcare units used tools
      for proactive analysis of patient safety risks. The risks identified most often
      were related to medication (100%), and infection (89.6%). The main solutions
      identified were related to protocols for medication review, hand hygiene
      training, alcohol-based hand-wash solutions, and interventions on patients on
      polypharmacy. CONCLUSIONS: A large proportion of adverse events that occur in
      health care are preventable, thus it is necessary to establish preventive
      strategies. This study shows the solutions for Primary Health Care units to
      prevent adverse events, and other patient safety risks not found in other studies
      (related to the use of medical devices/equipment).

PMID- 22459278
TI  - [Advantages and disadvantages of incorporating qualitative methodology in the
      evaluation of health services. A practical case: evaluation of a high-resolution
      clinic].
AB  - OBJECTIVE: We examined the usefulness of incorporating a qualitative phase in the
      evaluation of the quality of care in a high-resolution medical service carried
      out with quantitative methods. DESIGN AND METHODS: A quantitative research was
      performed using a structured questionnaire and selecting interviewees by
      systematic randomized sampling methods (n=320). In addition, a qualitative
      research was carried on through semi-structured interviews with patients selected
      by convenience criteria (n=11), observations in the care assistance circuit, and
      a group interview with health professionals working in the service. A
      multidisciplinary research team conducted an individual analysis of the
      information collected in both quantitative and qualitative phases. Subsequently,
      three meetings based on group brainstorming techniques were held to identify the
      diverse contributions of each of the methodologies employed to the research,
      using affinity graphs to analyse the different results obtained in both phases
      and evaluate possible bias arising from the use of qualitative methods. RESULTS:
      Qualitative research allowed examining specific aspects of the health care
      service that had been collected in the quantitative phase, harmonizing the
      results obtained in the previous phase, giving in-depth data on the reasons for
      patient dissatisfaction with specific aspects, such as waiting times and
      available infrastructures, and identifying emerging issues of the service which
      had not been previously assessed. CONCLUSIONS: Overall, the qualitative phase
      enriched the results of the research. It is appropriate and recommendable to
      incorporate this methodological approach in research aimed at evaluating the
      quality of the service in specific health care settings, since it is provided
      first hand, by the voice of the customer.

PMID- 22459279
TI  - Evaluation of elemental composition of sediments from the Adriatic Sea by using
      EDXRF technique.
AB  - 723 sediment samples collected along the eastern Adriatic coast have been
      analyzed using Energy Dispersive X-Ray Fluorescence. Factor Analysis and GIS have
      been used for the evaluation of the resulting data base containing information on
      K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, Ga, As, Br, Rb, Sr, Y, and Pb concentration
      levels in order to find spatial relationships in distribution of measured
      elements. This study can be used to identify background values and to evaluate
      sediment quality standards.

PMID- 22459280
TI  - Procedure for statistical analysis of one-parameter discrepant experimental data.
AB  - A new, Mandel-Paule-type procedure for statistical processing of one-parameter
      discrepant experimental data is described. The procedure enables one to estimate
      a contribution of unrecognized experimental errors into the total experimental
      uncertainty as well as to include it in analysis. A definition of discrepant
      experimental data for an arbitrary number of measurements is introduced as an
      accompanying result. In the case of negligible unrecognized experimental errors,
      the procedure simply reduces to the calculation of the weighted average and its
      internal uncertainty. The procedure was applied to the statistical analysis of
      half-life experimental data; Mean half-lives for 20 actinides were calculated and
      results were compared to the ENSDF and DDEP evaluations. On the whole, the
      calculated half-lives are consistent with the ENSDF and DDEP evaluations.
      However, the uncertainties calculated in this work essentially exceed the ENSDF
      and DDEP evaluations for discrepant experimental data. This effect can be
      explained by adequately taking into account unrecognized experimental errors.

PMID- 22459282
TI  - In vitro antimicrobial activity of pannarin alone and in combination with
      antibiotics against methicillin-resistant Staphylococcus aureus clinical
      isolates.
AB  - The in vitro antimicrobial activities of pannarin, a depsidone isolated from
      lichens, collected in several Southern regions of Chile (including Antarctica),
      was evaluated alone and in combination with five therapeutically available
      antibiotics, using checkerboard microdilution assay against methicillin-resistant
      clinical isolates strains of Staphylococcus aureus. MIC(90), MIC(50), as well as
      MBC(90) and MBC(50), were evaluated. A moderate synergistic action was observed
      in combination with gentamicin, whilst antagonism was observed in combination
      with levofloxacin. All combinations with erythromycin were indifferent, whilst
      variability was observed for clindamycin and oxacillin combinations. Data from
      checkerboard assay were analysed and interpreted using the fractional inhibitory
      concentration index and the response surface approach using the DeltaE model.
      Discrepancies were found between both methods for some combinations. In order to
      asses cellular lysis after exposure to pannarin, cell membrane permeability assay
      was performed. The treatment with pannarin produces bactericidal activity without
      significant calcein release, consistent with lack of lysis or even significant
      structural damage to the cytoplasmic membrane. Furthermore, pannarin shows low
      hemolytic activity and moderate cytotoxic effect on peripheral blood mononuclear
      cells. These findings suggest that the natural compound pannarin might be a good
      candidate for the individualization of novel templates for the development of new
      antimicrobial agents or combinations of drugs for chemotherapy.

PMID- 22459281
TI  - Mitochondrial Ca(2+) signals in autophagy.
AB  - Macroautophagy (autophagy) is a lysosomal degradation pathway that is conserved
      from yeast to humans that plays an important role in recycling cellular
      constituents in all cells. A number of protein complexes and signaling pathways
      impinge on the regulation of autophagy, with the mammalian target of rapamycin
      (mTOR) as the central player in the canonical pathway. Cytoplasmic Ca(2+)
      signaling also regulates autophagy, with both activating and inhibitory effects,
      mediated by the canonical as well as non-canonical pathways. Here we review this
      regulation, with a focus on the role of an mTOR-independent pathway that involves
      the inositol trisphosphate receptor (InsP(3)R) Ca(2+) release channel and Ca(2+)
      signaling to mitochondria. Constitutive InsP(3)R Ca(2+) transfer to mitochondria
      is required for autophagy suppression in cells in nutrient-replete media. In its
      absence, cells become metabolically compromised due to insufficient production of
      reducing equivalents to support oxidative phosphorylation. Absence of this Ca(2+)
      transfer to mitochondria results in activation of AMPK, which activates mTOR
      independent pro-survival autophagy. Constitutive InsP(3)R Ca(2+) release to
      mitochondria is an essential cellular process that is required for efficient
      mitochondrial respiration, maintenance of normal cell bioenergetics and
      suppression of autophagy.

PMID- 22459283
TI  - Multiple duodenal stromal tumors revealing type 1 neurofibromatosis: an
      indication for pancreas-preserving duodenectomy.

PMID- 22459284
TI  - Intraoperative factors affecting renal outcome after open repair of suprarenal
      aortic aneurysms.
AB  - BACKGROUND: The open repair of suprarenal aortic aneurysm requires supraceliac
      aortic cross-clamping and separate renal artery reconstruction. The aim of this
      study was to determine the intraoperative factors responsible for postoperative
      renal dysfunction. METHODS: Between January 1, 2000 and May 31, 2010, 54
      suprarenal aortic aneurysms were repaired at our center (mean age of the
      patients, 66 +/- 8 years). All cases were operated through a left retroperitoneal
      approach without left renal vein division. Acute kidney injury was defined as a
      50% increase of serum creatinine level from the preoperative baseline
      concentration. Perioperative variables were tested to be correlated with renal
      dysfunction (Spearman rank). RESULTS: The ischemic time was 28 +/- 8 minutes for
      the mesentery and the right kidney and 63 +/- 16 minutes for the left kidney. The
      total aortic clamping time was 115 +/- 27 minutes. The volume of autologous
      transfusion was 957 +/- 479 mL, allogeneic transfusion was 936 +/- 473 mL, and
      colloids and crystalloids was 7,194 +/- 2,201 mL. Two patients died. Acute kidney
      injury occurred in 15 patients, with complete recovery at discharge. The
      autologous blood transfusion volume (P = 0.009, r = 0.36) and the total aortic
      clamping time (P = 0.04, r = 0.30) were correlated with renal dysfunction.
      CONCLUSION: Postoperative renal dysfunction based on the variation in creatinine
      serum level was transient and requires further investigation using sensitive
      biomarkers for tubular ischemia.

PMID- 22459285
TI  - Blood transfusions in the surgical patient: a gift of life, but at what cost?

PMID- 22459286
TI  - Optimizing pancreatectomy outcomes: follow the evidence.

PMID- 22459287
TI  - Response of gut hormones after implantation of a reversible gastric restrictive
      device in different animal models.
AB  - BACKGROUND: Variable responses of gut hormones have been observed after bariatric
      procedures. The aim of the present study was to evaluate the ghrelin, glucagon
      like peptide 1 (GLP-1), and leptin levels in nonobese canine and obese rat models
      after weight loss owing to a reversible gastric restriction (RGR) device.
      METHODS: Mongrel dogs and obese Zucker rats were submitted to either surgical
      implantation or a sham operation and were followed up for 6 wk. The serum fasting
      ghrelin, GLP-1, and leptin levels in dogs were measured using enzyme-linked
      immunosorbent assay before and after surgical implantation and after implant
      removal. The protein expression of mucosa ghrelin, GLP-1, and leptin in the dog
      and rat stomach were measured using Western blotting. RESULTS: The RGR implant in
      dogs and rats resulted in a significant decrease in food intake and body weight.
      In the nonobese dog, the serum ghrelin level and mucosa ghrelin expression were
      significantly increased after surgical implantation (P < 0.05) and tended to
      recover after implant removal. In the obese rat, mucosa ghrelin expression
      decreased by about 27% (P = 0.06) 6 wk after implantation. A lower serum leptin
      level in dogs and lower mucosa leptin expression in dogs and rats was observed
      after surgical implantation compared with the sham procedure (P < 0.05). The RGR
      implant had no influence on the serum GLP-1 level in dogs or mucosa GLP-1
      expression in either animal model. CONCLUSIONS: Our results showed that ghrelin
      levels are downregulated with short-term RGR implantation in obese rats but
      upregulated in nonobese dogs, implying that the energy balance could be an
      important determinant of ghrelin level. The marked suppression of leptin in both
      animal models might contribute to the weight-reducing effect of the RGR implant.

PMID- 22459288
TI  - Preventive effect of G-CSF on acute lung injury via alveolar macrophage
      regulation.
AB  - BACKGROUND: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS)
      are devastating clinical syndromes associated with a high mortality rate. We
      examined the preventive effect of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) in a mouse ALI/ARDS model induced by
      lipopolysaccharide (LPS). MATERIALS AND METHODS: Mice were injected with LPS (10
      20 mg/kg) with or without rhG-CSF pretreatment (250 mg/kg/d). Survival rate,
      cytokine mRNA expression, and pathologic findings were examined. RESULTS: The 96
      h survival rate of the control group was 20%. Survival was significantly
      increased to 80% in rhG-CSF-treated animals. LPS-induced destruction of the
      alveolar structure was not observed in the rhG-CSF group. Pretreatment with rhG
      CSF led to significantly lower mRNA expression of TNF-alpha and IL-1beta in the
      lung 24 h after LPS administration and significantly higher IL-10 expression 96 h
      after LPS administration. Immunohistochemical analysis revealed that treatment
      with rhG-CSF also prevented the up-regulation of TNF-alpha and IL-1beta protein
      expression in alveolar macrophages. CONCLUSION: Treatment with rhG-CSF prevents
      the development of ALI/ARDS induced by LPS by affecting the production of pro-
      and anti-inflammatory cytokines and may be promising in clinical applications.

PMID- 22459290
TI  - "Pulling the plug"--management of meconium plug syndrome in neonates.
AB  - BACKGROUND: The significance of meconium plug syndrome (MPS) is unclear but has
      been associated with Hirschsprung's disease and magnesium tocolysis. We reviewed
      our experience to attempt to identify any potential association with these
      conditions and to review our outcomes. METHODS: Using the International
      Classification of Diseases, Ninth revision, code for meconium obstruction,
      patient charts were identified during the 1998-2008 period. A total of 61 cases
      of MPS were found, after excluding 7 of meconium ileus. Data regarding the
      hospital course and outcomes were collected and analyzed. RESULTS: Approximately
      30% of patients had spontaneous resolution of the meconium plug without any
      treatment. Of those patients requiring treatment, contrast barium enema was used,
      with 97% success. Only 2 patients required surgical intervention owing to
      worsening distension and subsequent peritonitis. When we stratified the patients
      according to gestational age of >36 and <36 wk, contrast barium enemas were
      performed 2.2 +/- 1.8 versus 8.6 +/- 7.8 d after birth (P = 0.003), respectively,
      and the lower gestational age patients had a longer length of stay. Contrast
      barium enema was still successful in 94% of patients with a gestational age of
      <36 wk. Magnesium tocolysis was noted in 16% of the cases, and Hirschsprung's
      disease was only found in 3.2% of patients. CONCLUSIONS: Patients with MPS have
      excellent outcomes, independent of gestational age. Contrast barium enema remains
      the initial diagnostic and treatment of choice for patients with MPS. Also,
      although previous reports have shown a link between magnesium tocolysis and
      Hirschsprung's disease with MPS, our experience suggests otherwise.

PMID- 22459291
TI  - Kupffer cell and platelet interactions in hepatic ischemia reperfusion.

PMID- 22459289
TI  - Ghrelin maintains the cardiovascular stability in severe sepsis.
AB  - BACKGROUND: Cardiovascular dysfunction, characterized by reduced cardiac
      contractility and depressed endothelium-dependent vascular relaxation, is common
      in severe sepsis. Although it is known that ghrelin produces beneficial effects
      following various adverse circulatory conditions, it remains unknown whether
      ghrelin increases cardiac contractility and improves vascular responsiveness to
      vasoactive agents in severe sepsis. METHODS: Male adult rats were subjected to
      sepsis by cecal ligation and puncture (CLP). At 5 h after CLP, a bolus
      intravenous injection of 2 nmol ghrelin was followed by a continuous infusion of
      12 nmol ghrelin via a primed mini-pump over 15 h. At 20 h after CLP (i.e., severe
      sepsis), the maximal rates of ventricular pressure increase (+dP/dt(max)) and
      decrease (-dP/dt(max)) were determined in vivo. In additional groups of animals,
      the thoracic aortae were isolated at 20 h after CLP. The aortae were cut into
      rings, and placed in organ chambers. Norepinephrine (NE) was used to induce
      vascular contraction. Dose responses for an endothelium-dependent vasodilator,
      acetylcholine (ACh), and an endothelium-independent vasodilator, nitroglycerine
      (NTG) were carried out. RESULTS: +dP/dt(max) and -dP/dt(max) decreased
      significantly at 20 h after CLP. Treatment with ghrelin significantly increased
      +dP/dt(max) and -dP/dt(max) by 36% (P < 0.05) and 35% (P < 0.05), respectively.
      Moreover, NE-induced vascular contraction and endothelium-dependent (ACh-induced)
      vascular relaxation decreased significantly at 20 h after CLP. Administration of
      ghrelin, however, increased NE-induced vascular contraction and ACh-induced
      vascular relaxation. In contrast, no significant reduction in NTG-induced
      vascular relaxation was seen in rats with severe sepsis irrespective of ghrelin
      treatment. CONCLUSIONS: Ghrelin may be further developed as a useful agent for
      maintaining cardiovascular stability in severe sepsis.

PMID- 22459292
TI  - Interleukin-5 is a potential mediator of angiotensin II-induced aneurysm
      formation in apolipoprotein E knockout mice.
AB  - BACKGROUND: The aim of this study was to evaluate alterations in Th1 and Th2
      cytokines during experimental abdominal aortic aneurysm (AAA) formation. METHODS:
      AAAs were induced in apolipoprotein E null mice by infusing angiotensin II (Ang
      II, 1000 ng/kg/min). Aortic homogenates were assessed at 0, 7, 14, and 28 d (n =
      11/time point) for select Th1 and Th2 cytokines by ELISA. Additional mice had co
      administration of anti-IgG (n = 20) or anti-IL-5 (n = 20) and were assessed at 28
      d for AAA. Aortic homogenates were assessed for MMP-2 and MMP-9 expression. Mouse
      aortic SMC (MASMC) and peritoneal-derived macrophages were treated with IL-5 (0
      40 ng/mL), and cell extracts and media (0-48 h) were assessed for MMP-2 and MMP-9
      expression. RESULTS: Ang II infusion was associated with a 3.4-fold (P < 0.01)
      and 3.6-fold (P < 0.01) increase in IL-5 and IL-10 (respectively), and a 0.6-fold
      reduction in IL-6, by 7 d. Anti-IL-5, but not anti-IgG, ameliorated Ang II
      induced AAA formation. Up-regulation of MMP-2 and MMP-9 was observed in
      aneurysmal aortas, but not in the aortas obtained from mice treated with anti-IL
      5. IL-5 stimulation of MASMC increased MMP-2 and MMP-9 mRNA (2.1-fold and 2.7
      fold, respectively, P < 0.01) and protein (1.6-fold and 1.9-fold, respectively, P
      < 0.01) by 24 h. IL-5 stimulation of macrophages did not alter MMP expression.
      CONCLUSIONS: Ang II induces increased Th2 cytokines IL-5 and IL-10 early in the
      course of experimental AAA formation, and inhibition of IL-5 prevents AAA
      formation suggesting an important role. While IL-5 is capable of up-regulating
      MMP-2 and MMP-9 expression in MASMC, investigations into alternate roles in AAA
      formation is warranted.

PMID- 22459293
TI  - Pharmacotherapy for traumatic spinal cord injury: the science behind the promise.

PMID- 22459294
TI  - The impact of race and ethnicity on the outcome of carotid interventions in the
      United States.
AB  - OBJECTIVE: Previous studies have demonstrated an adverse impact of African
      American race and Hispanic ethnicity on the outcomes of carotid endarterectomy
      (CEA), although little is known about the influence of race and ethnicity on the
      outcome of carotid angioplasty and stenting (CAS). The present study was
      undertaken to examine the influence of race and ethnicity on the outcomes of CEA
      and CAS in contemporary practice. METHODS: The nationwide inpatient sample (2005
      2008) was queried using International Classification of Diseases-9 codes for CEA
      and CAS in patients with carotid artery stenosis. The primary outcomes were
      postoperative death or stroke. Multivariate analysis was performed adjusting for
      age, gender, race, comorbidities, high-risk status, procedure type, symptomatic
      status, year, insurance type, and hospital characteristics. RESULTS: Overall,
      there were 347,450 CEAs and 47,385 CASs performed in the United States over the
      study period. After CEA, Hispanics had the greatest risk of mortality (P <
      0.001), whereas black patients had the greatest risk of stroke (P = 0.02)
      compared with white patients on univariate analysis. On multivariable analysis,
      Hispanic ethnicity remained an independent risk factor for mortality after CEA
      (relative risk 2.40; P < 0.001), whereas the increased risk of stroke in black
      patients was no longer significant. After CAS, there were no racial or ethnic
      differences in mortality. On univariate analysis, the risk of stroke was greatest
      in black patients after CAS (P = 0.03). However, this was not significant on
      multivariable analysis. CONCLUSION: Hispanic ethnicity is an independent risk
      factor for mortality after CEA. While black patients had an increased risk of
      stroke after CEA and CAS, this was explained by factors other than race. Further
      studies are warranted to determine if Hispanic ethnicity remains an independent
      risk factor for mortality after discharge.

PMID- 22459295
TI  - Glucose metabolism during the early "flow phase" after burn injury.
AB  - BACKGROUND: Burn injury (BI) is associated with insulin resistance (IR) and
      hyperglycemia which complicate clinical management. We investigated the impact of
      BI on glucose metabolism in a rabbit model of BI using a combination of positron
      emission tomography (PET) and stable isotope studies under euglycemic insulin
      clamp (EIC) conditions. MATERIALS AND METHODS: Twelve male rabbits were subjected
      to either full-thickness BI (B) or sham burn. An EIC condition was established by
      constant infusion of insulin, concomitantly with a variable rate of dextrose
      infusion 3 d after treatment. PET imaging of the hind limbs was conducted to
      determine the rates of peripheral O(2) and glucose utilization. Each animal also
      received a primed constant infusion of [6,6-(2)H(2)] glucose to determine
      endogenous glucose production. RESULTS: The fasting blood glucose in the burned
      rabbits was higher than that in the sham group. Under EIC conditions, the sham
      burn group required more exogenous dextrose than the B group to maintain blood
      glucose at physiological levels (22.2 +/- 2.6 versus 13.3 +/- 2.9 mg/min, P <
      0.05), indicating a state of IR. PET imaging demonstrated that the rates of O(2)
      consumption and (18)F 2-fluoro-2-deoxy-D-glucose utilization by skeletal muscle
      remained at similar levels in both groups. Hepatic gluconeogenesis determined by
      the stable isotope tracer study was found significantly increased in the B group.
      CONCLUSIONS: These findings demonstrated that hyperglycemia and IR develop during
      the early "flow phase" after BI. Unsuppressed hepatic gluconeogenesis, but not
      peripheral skeletal muscular utilization of glucose, contributes to hyperglycemia
      at this stage.

PMID- 22459296
TI  - Proper sample-weighted data analysis is required to confirm the association
      between blood cadmium concentration and lipid profile in Korean adults: re: Kim
      K. Blood cadmium concentration and lipid profile in Korean adults. Environ. Res.
      2011. doi:10.1016/j.envres.2011.12.008.

PMID- 22459297
TI  - Defining Alzheimer as a common age-related neurodegenerative process not
      inevitably leading to dementia.
AB  - Since the description by Alois Alzheimer, more than 50 years have passed during
      which senile dementia and pre-senile dementia have been considered Alzheimer
      disease (AD) on the basis of their common neuropathological and clinical
      manifestations. AD now covers pre-senile dementia, senile dementia, mild
      cognitive impairment and pre-clinical AD, all of them within the context of AD
      related pathology. However, there is still a gray area between normal aging with
      AD-related pathology and AD. Here it is proposed that Alzheimer (or alzheimer) is
      an age-related neurodegenerative process distinguished from normal aging by the
      presence of senile plaques and neurofibrillary tangles. Alzheimer affects about
      80% of individuals aged 65 years but dementia only occurs in a small percentage
      of individuals at this age; prevalence of dementia in Alzheimer increases to 25%
      in individuals aged 80 years. The concepts derived from the beta-amyloid
      hypothesis support beta-amyloid as a conductor in the pathogenesis of familial AD
      and as a prodding factor in sporadic AD. Moreover, seeding of beta-amyloid and
      truncated tau explains incorporation, enhancement and perpetuation of AD-related
      changes. Therefore, the earliest Alzheimer changes confined to selected regions
      are the first grounds and the main risk factor for developing dementia. The term
      Alzheimer embraces this assumption and likens its meaning to other degenerative
      biological processes, such as atherosclerosis, that may eventually progress to
      disease. In this context, the first stages of Alzheimer should be considered as
      primary targets of therapeutic intervention in order to prevent progression to
      diseased states.

PMID- 22459298
TI  - Effect of preoperative ejection fraction, left ventricular systolic dimension and
      hemoglobin level on survival after aortic valve surgery in patients with severe
      chronic aortic regurgitation.
AB  - Surgical indications in patients with severe chronic aortic regurgitation (AR)
      and normal left ventricular (LV) ejection fractions (EF) remain to be
      established. The aim of this study was to identify prognostic indicators after
      surgery in patients with severe AR and normal LV systolic function. Preoperative
      clinical and echocardiographic characteristics were evaluated in 284 consecutive
      patients with chronic severe AR who underwent aortic valve surgery. Of these
      patients, 169 had normal (>=50%) and 115 had depressed (<50%) preoperative LV
      EFs. All-cause mortality was observed for a median of 39.9 months. Of 284
      patients, 7 (4.4%) with normal LV EFs and 15 (12.0%) with depressed LV EFs died
      during follow-up after aortic valve surgery (p = 0.017). In patients with normal
      EFs, multivariate Cox regression analysis showed that large LV end-systolic
      dimension and low plasma hemoglobin level were independent predictors of
      postsurgical mortality. Receiver-operating characteristic analysis showed that LV
      end-systolic dimension >=45 mm and hemoglobin level <13.4 g/dl were the best cut
      off values for postoperative mortality. In conclusion, preoperative LV end
      systolic dimension and hemoglobin level are independent prognostic factors of
      survival after aortic valve surgery in patients with chronic severe AR and normal
      LV EFs.

PMID- 22459299
TI  - Distensibility and diameter of ascending aorta assessed by cardiac magnetic
      resonance imaging in adults with tetralogy of fallot or complete transposition.
AB  - Structural abnormalities of the medial aorta have been described for conotruncal
      defects (e.g., tetralogy of Fallot [TOF] and complete transposition of the great
      arteries (dextrotransposition [d]-TGA). In TOF, progressive aortic dilation is a
      frequent finding. In patients with d-TGA with an atrial switch, this problem is
      less often described. The aim of the present study was to compare the extent of
      dilative aortopathy and aortic distensibility in adults with an atrial switch
      procedure (n = 39) to that in adults with repaired TOF (n = 39) and controls (n =
      39), using cardiac magnetic resonance imaging. The groups were matched for age
      and gender. Diameters of the aorta indexed to the body surface area were
      significantly increased in the patients with d-TGA and TOF compared to that of
      the controls at the aortic sinus up to the level of the right pulmonary artery.
      On multivariate testing, the diagnosis of a conotruncal defect (beta = 0.260; p =
      0.003) and aortic regurgitant fraction (beta = 0.405; p <0.001) were independent
      predictors of an increased aortic sinus diameter. Ascending aorta distensibility
      was significantly reduced in those with d-TGA and TOF compared to controls: 3.6
      (interquartile range 1.5 to 4.4) versus 2.8 (interquartile range 2.0 to 3.7)
      versus 5.5 (interquartile range 4.8 to 6.9) *10(-3) mm Hg(-1) (p <0.001). The
      independent predictors of ascending aorta distensibility were the diagnosis of a
      conotruncal defect (p <0.001) and age (p = 0.028). In conclusion, intrinsic
      aortopathy, manifested as increased ascending aortic diameters and reduced
      ascending aortic distensibility, is not only evident in adults with TOF, but also
      in adults with d-TGA and an atrial switch procedure. Long-term follow-up is
      needed to monitor the aortic size in both patient groups.

PMID- 22459300
TI  - Relation between hemoglobin a(1c) and outcomes in heart failure patients with and
      without diabetes mellitus.
AB  - In patients with diabetes mellitus (DM) in the general population, elevated
      glycosylated hemoglobin (HbA(1c)) increases the risk for developing heart failure
      (HF). However, in patients with established HF, the association of HbA(1c) level
      with outcomes is not well established. The aim of this study was to investigate
      the relation between HbA(1c) and outcomes in patients with HF with and without
      DM. A total of 845 patients with advanced HF followed at the Ahmanson-UCLA
      Cardiomyopathy Center were studied, stratified by the presence (n = 358) or
      absence (n = 487) of DM and by DM-specific HbA(1c) quartiles (patients with DM:
      Q1 <=6.4%, Q2 6.5% to 7.2%, Q3 7.3% to 8.5%, and Q4 >=8.6%; patients without DM:
      Q1 <=5.6%, Q2 5.7% to 6.0%, Q3 6.1% to 6.5%, and Q4 >=6.6%). The primary outcomes
      analyzed were death and death or urgent heart transplantation. In the cohort with
      DM, 2-year event-free survival was 61% and 65% in Q3 and Q4 compared to 48% and
      42% in Q1 and Q2 (p = 0.005). In the cohort without DM, there was no difference
      in outcomes by HbA(1c) quartile. Risk-adjusted analysis in the diabetic cohort
      showed significantly increased hazard ratios for death or urgent heart
      transplantation in Q1 and Q2 compared to Q4. For every unit HbA(1c) increase,
      there was a 15% decreased hazard ratio of death or urgent heart transplantation
      and all-cause mortality (p = 0.006 and p = 0.036, respectively). In the cohort
      without DM, multivariate models revealed similar hazard ratios among HbA(1c)
      quartiles. In conclusion, in this cohort of patients with advanced HF, higher
      HbA(1c) levels were associated with improved outcomes in patients with DM. This
      relation was not observed in patients without DM. Further investigations into
      mechanisms underlying the relation between HbA(1c), DM, and survival in advanced
      HF are warranted.

PMID- 22459301
TI  - Frequency of congenitally bicuspid aortic valves in patients >=80 years of age
      undergoing aortic valve replacement for aortic stenosis (with or without aortic
      regurgitation) and implications for transcatheter aortic valve implantation.
AB  - The purpose of the present report was to determine the frequency of a
      congenitally bicuspid aortic valve in patients >=80 years of age old with aortic
      stenosis (AS) severe enough to warrant aortic valve replacement. Transcatheter
      aortic valve implantation (TAVI) has traditionally been reserved for patients
      >=80 years of age with severe AS involving a 3-cuspid aortic valve.
      Traditionally, AS involving a 2-cuspid aortic valve has been a contraindication
      to TAVI. We examined operatively excised stenotic aortic valves in 364 patients
      aged >=80 years to determine the frequency of an underlying congenitally bicuspid
      aortic valve. Of the 347 octogenarians and 17 nonagenarians, 78 (22%) and 3 (18%)
      had stenotic congenitally bicuspid aortic valves, respectively. In conclusion,
      because the results of TAVI are less favorable in patients with stenotic
      congenitally bicuspid valves than in patients with stenotic tricuspid aortic
      valves, proper identification of the underlying aortic valve structure is
      important when considering TAVI as a therapeutic procedure for AS in older
      patients.

PMID- 22459302
TI  - Right ventricular and pulmonary arterial dimensions in adults with osteogenesis
      imperfecta.
AB  - We examined right ventricular (RV) and ascending pulmonary artery (PA1)
      dimensions in adults with osteogenesis imperfecta (OI). The survey included 99
      adults with OI divided in 3 clinical types (I, III, and IV) and 52 controls. RV
      and PA1 dimensions were measured by echocardiography and indexed for body surface
      area. Scoliosis was registered, and spirometry was performed in 75 patients with
      OI. All RV dimensions indexed by body surface area were significantly larger in
      the OI group compared to controls (RV basal dimension 1.9 +/- 0.5 vs 1.7 +/- 0.3
      cm/m(2), p <0.05; RV midcavity dimension 1.7 +/- 0.5 vs 1.5 +/- 0.3 cm/m(2), p
      <0.05; RV longitudinal dimension 4.3 +/- 1.1 vs 4.0 +/- 0.9 cm/m(2), p <0.05). RV
      outflow tract (RVOT) proximal diameter (1.8 +/- 0.4 vs 1.5 +/- 0.2 cm/m(2), p
      <0.05), RVOT distal diameter (1.2 +/- 0.2 vs 1.0 +/- 0.1 cm/m(2), p <0.05), and
      PA1 (1.2 +/- 0.3 vs 1.0 +/- 0.2 cm/m(2), p <0.05) were also significantly larger
      in the OI group. Furthermore, all RV dimensions and PA1 were significantly larger
      in patients with OI type III compared to patients with OI types I and IV and
      controls. There were no differences in RV, RVOT, or PA1 dimensions between
      patients presenting a restrictive ventilatory pattern (n = 11) and patients a
      normal ventilatory pattern. Scoliosis was registered in 42 patients. Patients
      with OI type III had greater RV and PA1 dimensions compared to controls and
      patients with OI types I and IV. Impaired ventilatory patterns and scoliosis did
      not have any impact on RV dimensions in these patients. In conclusion, patients
      with OI had increased RV and PA1 dimensions compared to the control group.

PMID- 22459303
TI  - Coronary microvascular function and cortical pain processing in patients with
      silent positive exercise testing and normal coronary arteries.
AB  - ST-segment depression during exercise stress testing in asymptomatic subjects
      showing normal coronary arteries is considered a "false-positive" result.
      Coronary microvascular dysfunction, however, might be a possible cause of ST
      segment depression in these cases. We assessed the coronary blood flow response
      to adenosine and to cold pressor test in the left anterior descending artery,
      using transthoracic Doppler echocardiography in 14 asymptomatic subjects with
      exercise-induced ST-segment depression and normal coronary arteries (group 1), 14
      patients with microvascular angina (group 2), and 14 healthy subjects (group 3).
      Flow-mediated dilation was assessed in the brachial artery. Central pain
      processing was assessed using cortical laser evoked potentials during chest and
      right hand stimulation with 3 sequences of painful stimuli. The coronary blood
      flow response to adenosine was 1.8 +/- 0.4, 1.9 +/- 0.5, and 3.1 +/- 0.9 in
      groups 1, 2, and 3, respectively (p <0.001). The corresponding coronary blood
      flow responses to the cold pressor test were 1.74 +/- 0.4, 1.53 +/- 0.3, and 2.3
      +/- 0.6 (p <0.001). The flow-mediated dilation was 5.5 +/- 2.3%, 4.6 +/- 2.4%,
      and 9.8 +/- 1.2% in the 3 groups, respectively (p <0.001). The laser evoked
      potential N2/P2 wave amplitude decreased throughout the 3 sequences of
      stimulation in groups 1 and 3 but not in group 2 (chest, -19 +/- 22%, +11 +/- 42%
      and -36 +/- 12%, p <0.001; right hand, -22 +/- 25%, +12 +/- 43% and -30 +/- 20%,
      p = 0.009; in groups 1, 2, and 3). In conclusion, exercise stress test-induced ST
      segment depression in asymptomatic subjects with normal coronary arteries cannot
      be considered as a simple false-positive result, because it can be related to
      coronary microvascular dysfunction. The different symptomatic state compared to
      patients with microvascular angina can, at least in part, be explained by
      differences in cortical processing of neural pain stimuli.

PMID- 22459304
TI  - Usefulness of cardiovascular magnetic resonance imaging of the superficial
      femoral artery for screening patients with diabetes mellitus for atherosclerosis.
AB  - Cardiovascular magnetic resonance (CMR) of the superficial femoral artery (SFA)
      allows direct and noninvasive visualization of atherosclerotic plaque burden. We
      examined atherosclerosis in 3 groups of patients without history or symptoms of
      peripheral arterial disease with varying expected burdens: those with diabetes
      mellitus (DM) and known coronary artery disease (CAD) (n = 24), those with DM and
      a high prevalence of CAD risk factors (n = 20), and controls of similar age
      without DM or CAD and few CAD risk factors (n = 15). We also assessed the
      diagnostic accuracy of this technique to differentiate among these 3 groups. T1
      weighted spin-echocardiographic images were used to measure mean wall thickness
      (WT) and total wall volume indexed to total vessel volume. Diagnostic accuracy
      was assessed by area under receiver operating characteristics curve analysis.
      Patients with DM plus risk factors and DM plus CAD had higher mean WT (1.28 and
      1.37 mm) and mean indexed wall volume (0.53 and 0.56) compared to controls (mean
      WT 1.16 mm and mean indexed wall volume 0.45; p <0.010 for all comparisons). Mean
      WT and indexed wall volume showed good diagnostic accuracy in discriminating
      controls from those with DM plus CAD (areas under curve 0.85 and 0.87,
      respectively, p <0.001), whereas only indexed wall volume discriminated DM plus
      risk factors from controls (area under curve 0.82, p <0.001). Neither could
      discriminate between DM plus risk factors and DM plus CAD. In conclusion,
      patients with DM plus risk factors and DM plus CAD had significantly greater
      atherosclerotic burden in the SFA on CMR imaging than controls of similar age,
      with good diagnostic accuracy in differentiating these groups. The high
      reproducibility and reliability of CMR of the SFA may facilitate improved
      assessment of atherosclerosis prevalence and progression/regression in studies of
      novel therapies.

PMID- 22459305
TI  - Comparison of coronary flow velocity reserve measurement by transthoracic Doppler
      echocardiography with 320-row multidetector computed tomographic coronary
      angiography in the detection of in-stent restenosis in the three major coronary
      arteries.
AB  - We sought to compare the diagnostic accuracy and feasibility of coronary flow
      velocity reserve (CFVR) measurement using transthoracic Doppler echocardiography
      (TTDE) and 320-row multidetector computed tomographic coronary angiography (CTCA)
      for predicting in-stent restenosis (ISR). We enrolled 126 consecutive patients
      with 309 implanted coronary stents in the 3 major coronary arteries. TTDE and
      CTCA were performed within the 2-week period before follow-up invasive coronary
      angiography. Binary ISR was defined as percent diameter stenosis >=50% on
      invasive coronary angiogram. A CFVR <2.0 using TTDE and a narrowing of >=50%
      measured with CTCA were the thresholds indicating the presence of binary ISR.
      Presence of ISR using invasive coronary angiography was observed in 26 (8%)
      stents and 26 (14%) vessels. Feasibilities of CFVR measurement and CTCA for
      predicting ISR in the 3 major vessels were 94% and 91%, respectively. A CFVR <2.0
      revealed a 95% diagnostic accuracy with sensitivity of 87%, specificity of 96%,
      positive predictive value of 77%, and negative predictive value of 98%.
      Diagnostic accuracy of CTCA was comparable to that of CFVR measurement; however,
      CTC angiographic results were confounded by metal artifacts in the assessment of
      small-diameter stents. In conclusion, noninvasive CFVR measurement has high
      feasibility and accuracy for predicting ISR and is comparable to 320-row CTCA.

PMID- 22459306
TI  - Knowledge of and preference for advance care planning by adults with congenital
      heart disease.
AB  - Congenital heart disease (CHD) is a chronic illness. Few adults with CHD are
      cured and those with disease of moderate or great complexity remain at risk of
      premature death. Current adult CHD guidelines recommend that providers encourage
      their patients to complete advance directives. We evaluated the prevalence of
      completed advance directives by and the preference for information about life
      expectancy of outpatients at a large adult CHD program. Two hundred patients with
      CHD (52% men, 35 +/- 15 years old, range 18 to 79, 81% with disease of moderate
      or great complexity) completed a survey that assessed knowledge of advance
      directives and nature of and preferences for advance care planning. Only 5% of
      patients reported that they had completed advance directives; 56% had never heard
      of them. However, most patients (87%) reported that they would prefer to have an
      advance directive available if they were dealing with their own dying and were
      unable to speak for themselves. Patients who had formally identified substitute
      decision makers (n = 34) were typically older (47 +/- 16 vs 33 +/- 13 years, p
      <0.001) and more likely to have partners (30% vs 6%, p <0.001). Most patients
      (70%) reported that they wanted general information about the average life
      expectancy for patients with their heart condition. In conclusion, in contrast to
      recommendations from published guidelines, advance care planning documents are
      infrequently completed by outpatients. Health care providers caring for patients
      with CHD should educate their patients about advance directives and assist them
      in preparing formal end-of-life-planning documents.

PMID- 22459307
TI  - Long-term cardiac remodeling and arrhythmias in nonelite marathon runners.
AB  - Long-term endurance sports are associated with atrial remodeling and atrial
      arrhythmias. More importantly, high-level endurance training may promote right
      ventricular (RV) dysfunction and complex ventricular arrhythmias. We investigated
      the long-term consequences of marathon running on cardiac remodeling as a
      potential substrate for arrhythmias with a focus on the right heart. We invited
      runners of the 2010 Grand Prix of Bern, a 10-mile race. Of 873 marathon and
      nonmarathon runners who applied, 122 (61 women) entered the final analysis.
      Subjects were stratified according to former marathon participations: control
      group (nonmarathon runners, n = 34), group 1 (1 marathon to 5 marathons, mean
      2.7, n = 46), and group 2 (>=6 marathons, mean 12.8, n = 42). Mean age was 42 +/-
      7 years. Results were adjusted for gender, age, and lifetime training hours.
      Right and left atrial sizes increased with marathon participations. In group 2,
      right and left atrial enlargements were present in 60% and 74% of athletes,
      respectively. RV and left ventricular (LV) dimensions showed no differences among
      groups, and RV or LV dilatation was present in only 2.4% or 4.3% of marathon
      runners, respectively. In multiple linear regression analysis, marathon
      participation was an independent predictor of right and left atrial sizes but had
      no effect on RV and LV dimensions and function. Atrial and ventricular ectopic
      complexes during 24-hour Holter monitoring were low and equally distributed among
      groups. In conclusion, in nonelite athletes, marathon running was not associated
      with RV enlargement, dysfunction, or ventricular ectopy. Marathon running
      promoted biatrial remodeling.

PMID- 22459308
TI  - Relation of ventricular ectopic complexes to QTc interval on ambulatory
      electrocardiograms in Williams syndrome.
AB  - Williams syndrome (WS) is a congenital, developmental disorder affecting 1 in
      8,000 live births. The corrected QT (QTc) interval is prolonged in 13% of
      patients with WS. No data exist characterizing the ambulatory
      electrocardiographic findings in WS. A retrospective review of all patients with
      WS evaluated at our institution from January 1, 1980 to December 31, 2007 was
      performed. Patients with >=1 ambulatory electrocardiogram (AECG) with sinus
      rhythm and measurable intervals were included. QTc measurements were made at the
      minimum and maximum heart rate. Logistic regression analysis was used to evaluate
      the correlation of ventricular ectopic complexes with QTc measurements. A
      statistical probability of p <0.05 was considered significant. Of 270 patients
      identified, 32 had AECGs available for review. Complete data were available for
      56 AECGs from 26 patients (15 female; 58%). Their mean age was 15.6 +/- 7.2 years
      at the initial AECG and 20.6 +/- 8.6 years for all AECGs. The QTc interval
      increased with increasing heart rate. Ventricular premature complexes occurred in
      40 (73%) of 56 AECGs and 21 (81%) of 26 patients. Ventricular tachycardia
      occurred in 5 (9%) of 56 AECGs and 4 (15%) of 26 patients. The mean length of
      ventricular tachycardia was 3.6 +/- 0.5 beats at a rate of 171 +/- 40 beats/min.
      The QTc interval at the minimum heart rate correlated directly with age (p
      <0.001), total ventricular premature complexes (p = 0.007), ventricular couplets
      (p = 0.002), and ventricular tachycardia (p = 0.011). The QTc interval at the
      maximum heart rate correlated directly with age (p <0.001), total ventricular
      premature complexes (p = 0.016), and ventricular couplets (p = 0.006). In
      conclusion, the QTc interval correlated with ventricular ectopic complexes in
      patients with WS. The type of ventricular ectopic complexes suggested an
      alternate etiology of the QTc prolongation seen in WS from that seen in
      congenital long QT syndrome.

PMID- 22459309
TI  - Usefulness of intravenous adenosine in idiopathic pulmonary arterial hypertension
      as a screening agent for identifying long-term responders to calcium channel
      blockers.
AB  - Although intravenous adenosine is recommended for acute vasodilator testing in
      patients with pulmonary hypertension, long-term outcomes in acute responders
      treated with calcium channel blockers (CCBs) who are identified by adenosine
      remain unknown. In this study, the value of adenosine for identifying long-term
      responders to CCBs was investigated in patients with idiopathic pulmonary
      arterial hypertension (IPAH). All acute responders were subsequently treated with
      high-dose CCB monotherapy, and 6-minute walk distances, hemodynamic data, and
      World Health Organization functional classifications were followed. Nine of 104
      patients exhibited an acute response with intravenous adenosine (8.7%, 95%
      confidence interval 3.2 to 14.2). After 12 months of follow-up, all acute
      responders were still alive; however, only 6 patients showed sustained
      hemodynamic improvement (5.8%, 95% confidence interval 2 to 13). Three patients
      had failed CCB monotherapy and bosentan was added to their treatment. Mean
      tolerated dose of intravenous adenosine was 142 +/- 49 MUg/kg/min. No life
      threatening adverse events were observed and only 2 patients of the nonresponders
      exhibited a 20% decrease in mean systemic arterial pressure. In nonresponders, 1-
      and 3-year survival rates were 89% and 75%, respectively. In conclusion, acute
      vasodilator testing with intravenous adenosine was safe and able to screen
      responders to CCB therapy in patients with IPAH. Long-term CCB responders
      accounted for about 5.8% of patients with IPAH.

PMID- 22459311
TI  - Dairy consumption and working memory performance in overweight and obese adults.
AB  - All individuals will experience some degree of cognitive impairment in their
      later years. Diet is one readily modifiable factor that may influence cognitive
      function and psychological well-being. Very little research has considered the
      potential role of dairy foods in modulating cognitive and psychological
      functions. The objective of this study was to determine the effect of a high
      intake of reduced fat dairy food on cognitive performance. Overweight adults with
      habitually low dairy intakes (< two serves/day) were recruited for a 12 month
      crossover dietary intervention trial and randomised to a high (four serves/day)
      or low (one serve/day) intake of reduced fat dairy, crossing over to the
      alternate diet after 6 months. Participants were tested at the end of each 6
      month diet period on multiple measures of cognitive performance, including
      memory, information processing speed, executive function, attention and abstract
      reasoning. In 38 participants who completed the trial (average age=52+/-2 years;
      BMI=31.5+/-0.8 kg/m(2)), spatial working memory performance was marginally better
      following 6 months of the high dairy diet compared with the low dairy diet.
      Increasing the dairy intake of habitually low dairy consumers may have the
      potential to improve working memory.

PMID- 22459310
TI  - Relation of improvement in estimated glomerular filtration rate with atorvastatin
      to reductions in hospitalizations for heart failure (from the Treating to New
      Targets [TNT] study).
AB  - Impaired kidney function often accompanies heart failure (HF) and is associated
      with a worse prognosis. This post hoc analysis of the Treating to New Targets
      (TNT) trial examined whether the observed decrease in HF hospitalizations with
      high- compared to low-dose atorvastatin could be related to improvements in
      kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular
      filtration rate (eGFR) measurements at baseline and 1 year and were included in
      this analysis. The association of change in year-1 eGFR and subsequent HF
      hospitalization was examined using Cox regression models. In total 218
      participants developed subsequent HF hospitalization. Little change in eGFR
      occurred over 1 year in the atorvastatin 10-mg group, whereas eGFR improved in
      the 80-mg group by 1.48 ml/min/1.73 m(2) (95% confidence interval 1.29 to 1.67, p
      <0.0001). Subsequent HF was preceded by a decrease in eGFR over 1 year compared
      to modest improvement in those without subsequent HF (-0.09 +/- 7.89 vs 0.81 +/-
      6.90 ml/min/1.73 m(2), p = 0.0015). After adjusting for baseline eGFR, each 5
      ml/min/1.73 m(2) increase in eGFR at 1 year was associated with a lower risk of
      subsequent HF hospitalization (hazard ratio 0.85, 95% confidence interval 0.77 to
      0.94, p = 0.002). This relation was independent of treatment effect or change in
      low-density lipoprotein cholesterol level at 1 year. In conclusion, treatment
      with high- compared to low-dose atorvastatin was associated with improvement in
      eGFR at 1 year, which was related to a decrease in subsequent HF hospitalization.
      This suggests that improvement in kidney function may be related to the
      beneficial effect of high-dose atorvastatin on HF hospitalization.

PMID- 22459312
TI  - Lymph node homing of T cells and dendritic cells via afferent lymphatics.
AB  - The continuous migration of immune cells is of utmost importance for the
      induction of both protective immunity as well as immunological tolerance.
      However, relatively little is known about the molecular cues that regulate the
      entry of immune cells from peripheral, nonlymphoid tissues into afferent lymph
      vessels and, in particular, their subsequent transmigration from afferent
      lymphatics into the parenchyma of draining lymph nodes (LNs). Here, we review the
      requirements for T cells and dendritic cells (DCs) to enter initial afferent
      lymph vessels of the skin. We discuss how these cells subsequently gain access to
      the paracortex of draining lymph nodes; a location that allows for efficient
      interaction between both cell populations, providing the right environment for
      the induction of immunity as well as tolerance.

PMID- 22459313
TI  - The effect of using prebiotic and probiotic products on intestinal micro-flora of
      the honeybee (Apis mellifera carpatica).
AB  - Maintaining bee colonies in a healthy state throughout the year is one of the
      main concerns of apiculture researchers. The phenomenon of disappearance of bee
      colonies is determined by several factors, one of which is bee disease. Due to
      the organizational structure of the bee colony, disease transmission is rapid,
      especially through infected food or via the nurse worker bees that feed the brood
      bees of the colony concerned. The practice of stimulating the bee colonies in
      spring using sugar syrup feeds with added prebiotic products (lactic acid or
      acetic acid) and probiotics (Lactobacillus acidophilus LA-14 and Bifidobacterium
      lactis BI-04) by using an Enterobiotic product (Lactobacillus casei), marketed as
      Enterolactis Plus, for three weeks, resulted in a significant reduction of the
      total number of bacteria in the digestive tracts of the bees, compared with the
      control group. By contrast, intestinal colonization with beneficial bacteria
      contained in probiotics products administered to the bees was observed. This
      resulted in an improved health status and bio productive index of the bee
      colonies studied.

PMID- 22459314
TI  - Early-onset versus typical childhood absence epilepsy: are they all the same
      thing?

PMID- 22459315
TI  - Epilepsy in mitochondrial disorders.
AB  - OBJECTIVES: Information about epilepsy in mitochondrial disorders is scarce
      although a number or syndromic and non-syndromic mitochondrial disorders
      frequently manifest with focal or generalized seizures. Aim of the review was to
      describe epilepsy in syndromic and non-syndromic mitochondrial disorders with
      epilepsy as a dominant or collateral feature of the phenotype. METHODS:
      Literature search via Pubmed using the key words "mitochondrial", "epilepsy",
      "seizures", and all acronyms of syndromic mitochondrial disorders. RESULTS:
      Syndromic mitochondrial disorders obligatory associated with epilepsy include
      Alpers-Huttenlocher-syndrome (AHS), ataxia neuropathy spectrum (ANS), Leigh
      syndrome, MELAS-syndrome, myoclonic epilepsy, myopathy, and sensory ataxia
      (MEMSA) syndrome, and MERRF-syndrome, Occasionally, epilepsy is a phenotypic
      feature in IOSCA, KSS, LHON, LBSL, or NARP, All types of seizures occur but most
      frequently generalized tonic-clonic seizures, partial seizures, myoclonic jerks,
      or West-syndrome was reported. Treatment of epilepsy in patients with
      mitochondrial disorders is not at variance from epilepsy of other causes but
      mitochondrion-toxicity of various antiepileptic drugs, such as valproic acid,
      carbamazepine etc. has to be considered to avoid severe complications or
      deterioration of the underlying disease. CONCLUSIONS: Epilepsy is a common
      phenotypic feature of syndromic as well as non-syndromic mitochondrial disorders.
      Treatment of epilepsy in mitochondrial disorders is not at variance from
      treatment of epilepsy due to other causes but mitochondrion-toxic drugs should be
      avoided.

PMID- 22459316
TI  - Neuropsychological outcome following minimal access subtemporal selective
      amygdalohippocampectomy.
AB  - PURPOSE: The present study provides a detailed account of neurocognitive outcome
      following minimal access subtemporal selective amygdalohippocampectomy (SAH) and
      establishes rates of neurocognitive decline in the largest sample to date. Use of
      a subtemporal surgical approach to SAH has been proposed to possibly reduce the
      risk for postoperative neurocognitive decline since lateral neocortical tissues
      is not resected and the temporal stem is preserved. The current study extends
      prior research with subtemporal SAH patients to include not only group level
      analyses but also analyses based on reliable change data. METHODS: Neurocognitive
      comparisons are made between 47 patients that underwent subtemporal SAH.
      Statistical comparisons were made between neurocognitive performance at the group
      level and with use of reliable change scores. RESULTS: Approximately 75% of
      patients were seizure free postoperatively. At the group level, there were no
      significant postoperative changes. For the left SAH patients, reliable change
      scores demonstrated a decline in approximately one third of patients for memory,
      verbal intellect, and naming. Right SAH patients showed decline primarily in
      memory. CONCLUSIONS: These results indicated good seizure control following
      subtemporal SAH with greatest risk for neurocognitive decline following dominant
      SAH and best cognitive outcome following non-dominant SAH. Findings demonstrated
      the importance of reliable change analyses that make individual based comparisons
      and take into account measurement error. Despite preservation of the lateral
      neocortical tissue and the temporal stem, subtemporal SAH presents a risk for
      cognitive decline in a notable portion of patients.

PMID- 22459317
TI  - Social support and mobility limitation as modifiable predictors of improvement in
      depressive symptoms in the elderly: results of a national longitudinal study.
AB  - Few national longitudinal studies have investigated the predictors of a better
      depression outcome in geriatric depression. This study examined the predictors of
      improvement in case-level depressive symptoms in the elderly. In this prospective
      cohort and population-based study in Taiwan, 206 non-demented and case-level
      depressed subjects aged 65 and older were interviewed at baseline in 2003 and
      follow-up in 2007. The independent variables included demographics, chronic
      medical diseases, and health-related behaviors assessed at baseline. The
      dependent variable was depressive symptoms, assessed using the 10-item short form
      of the Center for Epidemiologic Studies Depression Scale (CESD-10) assessed at
      follow-up. Multivariate analyses were used to identify the predictors of
      improvement in depression. The independent predictors of improvement in
      depression over a 4-year follow-up period are more social support and fewer
      mobility limitations at baseline. With regards to practical health-related
      behaviors, the 2 items of social support most associated with improvement in
      depression were willingness of significant others to talk with you and
      satisfaction with dependence upon significant others; the 2 items of mobility
      limitations most associated with non-improvement of depression were difficulty in
      carrying things and squatting. These findings suggested that health-related
      behaviors were important to the depression outcome in the elderly; moreover,
      interventions to improve depression should include practical health-related
      behaviors aimed at these modifiable risk factors.

PMID- 22459318
TI  - Disability and co-morbidity in relation to frailty: how much do they overlap?
AB  - The purpose of this study was to examine the association of disability and co
      morbidity with frailty in older adults. 2305 participants aged 65+ from the
      second wave of the Canadian Study of Health and Aging (CSHA), a prospective
      population-based cohort study, comprised the study sample. Following a standard
      procedure, two different frailty index (FI) measures were constructed from 37
      deficits by dividing the recorded deficits by the total number of measures. One
      version excluded disability and co-morbidity items, the other included them. Time
      to death was measured for up to five years. Frailty was defined using either the
      frailty phenotype or a cut-point applied to each FI. Of people defined as frail
      using the frailty phenotype, 15/416 (3.6%) experienced neither disability nor co
      morbidity. Using 0.25 as the cut-point score for the FI (without disability/co
      morbidity) resulted in 101/1176 (8.6%) frail participants that had neither
      disability nor co-morbidity. Activities of daily living (ADL) limitations and co
      morbidities occurred more often among people with the highest levels of frailty.
      The first ADLs to become impaired with increasing frailty were bathing, managing
      medication, and cooking with more than 25% of older adults with a FI score
      (without disability/co-morbidity) >0.22 experiencing dependency on them. The
      hazard ratio (HR) per 0.1 increase in FI score was 1.25 (95% CI: 1.20-1.30) when
      disability and co-morbidity were included in the index and 1.21 (1.16-1.25) when
      they were not included. In conclusion, disability and co-morbidity greatly
      overlap with other deficits that might be used to define frailty and add to their
      ability to predict mortality.

PMID- 22459319
TI  - Usability of a daily noise exposure monitoring device for industrial workers.
AB  - OBJECTIVES: Usability is an important but often overlooked aspect of personal
      protective equipment technology. As part of a worksite intervention trial of a
      new technology for prevention of noise-induced hearing loss that allows workers
      to monitor their noise exposure inside of hearing protection on a daily basis, we
      studied the usability of the daily noise exposure monitoring device. METHODS: We
      conducted surveys and focus groups for workers enrolled in an intervention trial
      of daily use of a noise dosimeter with a microphone fitted inside of an
      individual's hearing protector (QuietDose). Volunteers completed a baseline and
      annual survey that included questions about perceived usability of the QuietDose
      device. Responses to usability questions on the annual survey were abstracted and
      compared to whether the individual was still using the device. Finally, 16 in
      depth focus groups were conducted with subjects to qualitatively explore common
      themes regarding the usability of the technology. RESULTS: Reported problems
      downloading data or starting and stopping the monitoring device and/or ear
      discomfort were associated with whether individuals chose to continue monitoring
      and downloading their noise exposure data. Perceived benefits of the technology
      included the perception that it could help preserve hearing. CONCLUSIONS: A novel
      technology that allows workers to record noise exposures inside of hearing
      protectors on a daily basis has been developed. Current users of the device
      report positive perception about how the device is helping them prevent noise
      induced hearing loss. However, in its current version, users reported a number of
      usability barriers that are associated with stopping use of the device. These
      barriers to use should be addressed as the technology progresses.

PMID- 22459320
TI  - Organic and elemental carbon filter sets: preparation method and interlaboratory
      results.
AB  - Carbonaceous aerosols play an important role in climate, visibility, air quality,
      and human health effects, and they have been routinely monitored in workplace and
      environmental settings. Different thermal analysis methods have been applied to
      determine the carbon content of carbonaceous aerosols. Good agreement between
      results for total carbon (TC) generally has been found, but the organic and
      elemental carbon (OC and EC) fractions determined by different methods often
      disagree. Measurement uncertainty is mainly due to pyrolysis and charring of OC
      sample components. Lack of reference materials has impeded progress on method
      standardization and understanding method biases. A relatively simple method for
      generating matched filter sets having known OC-EC contents is reported. After
      generation and analysis of each set to confirm agreement between filters, the
      filter sets were distributed to six laboratories for an interlaboratory
      comparison. Analytical results indicate a uniform carbon distribution for the
      filter sets and good agreement between the participating laboratories. Relative
      standard deviations (RSDs) for mean TC (OC + EC), OC, and EC results for seven
      laboratories were <10, 11, and 12% (respectively). Except for one EC result (RSD
      = 16%), RSDs reported by individual laboratories for TC, OC, and EC were <12%.
      The method of filter generation is generally applicable and reproducible.
      Depending on the application, different filter loadings and types of OC materials
      can be employed. Matched filter sets prepared by the described approach can be
      used for determining the accuracy of OC-EC methods and thereby contribute to
      method standardization.

PMID- 22459321
TI  - Local exhaust ventilation for the control of welding fumes in the construction
      industry--a literature review.
AB  - Arc welding is a common unit operation in the construction industry, where
      frequent changes in location and welding position make it more difficult to
      control fume exposures than in industries where fixed locations are the norm.
      Welders may be exposed to a variety of toxic airborne contaminants including
      manganese (Mn) and hexavalent chromium (CrVI). Local exhaust ventilation (LEV) is
      a well-known engineering control for welding fumes but has not been adopted
      widely in the construction industry. This literature review presents data on the
      performance of a variety of LEV systems for welding fume control from the
      construction (five references), shipyard (five references), and other industries.
      The studies indicate that LEV can reduce fume exposures to total particulate, Mn,
      and CrVI to levels below currently relevant standards. Field studies suggest that
      40-50% or more reduction in exposure is possible with portable or fixed LEV
      systems relative to natural ventilation but that correct positioning of the hood
      and adequate exhaust flow rates are essential. Successful implementation of
      extraction guns for gas metal arc welding (GMAW) and flux core arc welding has
      been demonstrated, indicating that a successful balance between extraction
      airflow and shielding gas requirements is possible. Work practices are an
      important part of achieving successful control of fume exposures; in particular,
      positioning the hood close to the arc, checking exhaust flow rates, and avoiding
      the plume. Further research is needed on hood size effects for controlling
      welding fume with portable LEV systems and identifying and overcoming barriers to
      LEV use in construction.

PMID- 22459322
TI  - Zonal responses of sensitive vs. tolerant wheat roots during Al exposure and
      recovery.
AB  - Aluminium (Al) irreversibly inhibits root growth in sensitive, but not in some
      tolerant genotypes. To better understand tolerance mechanisms, seedlings from
      tolerant ('Barbela 7/72' line) and sensitive ('Anahuac') Triticum aestivum L.
      genotypes were exposed to AlCl(3) 185 MUM for: (a) 24 h followed by 48 h without
      Al (recovery); (b) 72 h of continuous exposure. Three root zones were analyzed
      (meristematic (MZ), elongation (EZ) and hairy (HZ)) for callose deposition,
      reserves (starch and lipids) accumulation, endodermis differentiation and tissue
      architecture. Putative Al-induced genotoxic or cytostatic/mytogenic effects were
      assessed by flow cytometry in root apices. Tolerant plants accumulated less Al,
      presented less root damage and a less generalized callose distribution than
      sensitive ones. Starch and lipid reserves remained constant in tolerant roots but
      drastically decreased in sensitive ones. Al induced different profiles of
      endodermis differentiation: differentiation was promoted in EZ and HZ,
      respectively, in sensitive and tolerant genotypes. No ploidy changes or
      clastogenicity were observed. However, differences in cell cycle blockage
      profiles were detected, being less severe in tolerant roots. After Al removal,
      only the 'Barbela 7/72' line reversed Al-induced effects to values closer to the
      control, mostly with respect to callose deposition and cell cycle progression. We
      demonstrate for the first time that: (a) cell cycle progression is differently
      regulated by Al-tolerant and Al-sensitive genotypes; (b) Al induces callose
      deposition >3 cm above root apex (in HZ); (c) callose deposition is a transient
      Al-induced effect in tolerant plants; and (d) in HZ, endodermis differentiation
      is also stimulated only in tolerant plants, probably functioning in tolerant
      genotypes as a protective mechanism in addition to callose.

PMID- 22459323
TI  - Novel glutamate dehydrogenase genes show increased transcript and protein
      abundances in mature tomato fruits.
AB  - NAD(P)H-glutamate dehydrogenase (GDH, EC 1.4.1.3) contributes to the control of
      glutamate homeostasis in all living organisms. In bacteria and animals, GDH is a
      homohexamer allosterically regulated, whereas in plants NADH-GDH (EC 1.4.1.2) is
      also found as heterohexamer of alpha- and beta-subunits, but its regulation
      remains undefined. In tomato (Solanum lycopersicum), GDH activity increases
      during the fruit ripening along with the content of free glutamate, the most
      abundant amino acid of ripe fruit involved in conferring the genuine tomato
      flavour. In this work, novel Slgdh-NAD genes were identified in the recently
      deciphered tomato genome: three encoding the alpha-subunit (Slgdh-NAD;A1-3) and
      one additional gene encoding the beta-subunit of GDH (Slgdh-NAD;B1) isolated from
      a genomic library. These genes are located in different chromosomes. Slgdh-NAD;A1
      3 show conserved structures, whereas Slgdh-NAD;B1 includes a novel 5'
      untranslated exon. Slgdh-NAD;A1-3 transcripts were detected in all tomato tissues
      examined, showing the highest levels in mature green fruits, contrasting with
      Slgdh-NAD;B1 transcripts which were detected mainly in roots or in mature fruits
      when treated with glutamate, NaCl or salicylic acid. Analyses of GDH activity and
      protein distribution in different tissues of the Micro-Tom cultivar showed that
      only the active homohexamer of GDH beta-subunits was detected in roots while
      heterohexamers of GDH alpha- and beta-subunits were found in fruits. These
      results indicate that GDH beta-subunit could modulate the heteromeric isoforms of
      GDH in response to the environment and physiology of the tomato fruit. This
      information is relevant to manipulate glutamate contents in tomato fruits
      genetically.

PMID- 22459324
TI  - Evaluation of candidate reference genes for qPCR in maize.
AB  - Quantitative real-time PCR (qPCR) is a powerful tool to measure gene expression
      levels. Accurate and reproducible results are dependent on the correct choice of
      the reference genes for data normalization. To date, screenings evaluating
      candidate reference gene stability for expression studies in maize have not been
      reported. In the present work, we analyzed the expression patterns of 12 genes in
      a set of 20 maize samples, obtained from different tissues of plants grown at
      various experimental conditions. Using genorm(PLUS), NormFinder and BestKeeper
      algorithms, the expression stability of three "classical" reference genes, such
      as ACT, TUB and 18S rRNA, and the newly identified candidates, was assessed. With
      respect to the algorithms, our results showed similar performance among
      genorm(PLUS), NormFinder and BestKeeper in evaluating the suitability of
      reference genes. Our data therefore showed that the currently and widely used
      reference genes for data normalization in maize were not the most stable
      expressed transcripts. Five of the new putative reference genes (CUL, FPGS, LUG,
      MEP and UBCP) exhibited the highest expression stability according to all
      algorithms. In conclusion, with this study, we provide a list of validated
      reference genes and their relative primer sequences to conduct reliable qPCR
      experiments in maize.

PMID- 22459325
TI  - Cycloheximide as a tool to investigate protein import in peroxisomes: a case
      study of the subcellular localization of isoprenoid biosynthetic enzymes.
AB  - Cytosolic background fluorescence is often observed when native low-abundance
      peroxisomal proteins carrying a weak peroxisomal targeting sequence are expressed
      as fluorescent fusion protein using a strong constitutive promoter in transiently
      transformed plant cells. This cytosolic fluorescence usually comes from the
      strong expression of the low-abundance proteins exceeding the peroxisome import
      efficiency. This often results in a misinterpretation of the protein subcellular
      localization, as there is doubt as to whether proteins are dually targeted to the
      cytosol and peroxisome or are exclusively localized to peroxisomes. To circumvent
      this experimental difficulty, the protein peroxisome import study can be
      optimized by de novo protein synthesis inhibition in transiently transformed
      cells using the translation inhibitor cycloheximide. This approach was used here
      successfully for the study of the subcellular localization of distinct plant
      isoprenoid biosynthetic enzymes, allowing us to clearly demonstrate that 5
      phosphomevalonate kinase, mevalonate 5-diphosphate decarboxylase and a short
      isoform of farnesyl diphosphate synthase from Catharanthus roseus are exclusively
      localized to peroxisomes.

PMID- 22459326
TI  - Molecular characterization of two ethylene response factor genes in sweetpotato
      that respond to stress and activate the expression of defense genes in tobacco
      leaves.
AB  - Two ethylene response factor (ERF) genes, IbERF1 and IbERF2, were isolated from a
      library of expressed sequence tags (EST) prepared from suspension-cultured cells
      and dehydration-treated fibrous roots of sweetpotato (Ipomoea batatas). The
      deduced IbERFs contained a nuclear localization signal and the AP2/ERF DNA
      binding domain. RT-PCR analysis revealed that IbERF1 was expressed abundantly
      during the growth of suspension-cultured cells, whereas the expression levels of
      IbERF2 transcripts were high in fibrous, thick pigmented roots. Two ERF genes
      also showed different responses to various types of abiotic stress and pathogen
      infection. Transient expression of the two ERF genes in tobacco (Nicotiana
      tabacum) leaves resulted in increased transcript levels of the pathogenesis
      related 5 (PR5) gene, the early response to dehydration ten gene (ERD10), the
      CuZn superoxide dismutase gene (CuZnSOD) and the catalase gene (CAT). It is
      suggested that the two ERF genes play roles in the stress defense-signaling
      pathway as transcriptional regulators of the PR5, ERD10, CuZnSOD and CAT genes.

PMID- 22459327
TI  - Relationship between approach and avoidance inclinations to use alcohol and
      treatment outcomes.
AB  - BACKGROUND: Despite growing recognition of the importance of multidimensional
      assessments of craving, little is known about how both approach and avoidance of
      alcohol inclinations change during the course of treatment, or relate to
      treatment outcomes. The current study examined the relationship between approach
      inclinations, avoidance inclinations, and treatment outcomes in individuals
      seeking treatment for alcohol dependence, and investigated whether changes in
      approach and avoidance ratings were associated with changes in drinking. METHODS:
      Individuals (n=81) seeking treatment for alcohol dependence were randomized to
      receive either 12-sessions of cognitive-behavioral therapy plus healthy living
      skills or 12-sessions of cognitive-behavioral therapy plus affect regulation
      training. Participants provided pre- and post- treatment scores on various
      measures including drinking behaviors and approach and avoidance inclinations to
      use alcohol. RESULTS: Results indicated that both approach and avoidance
      inclinations were uniquely and significantly associated with problem recognition,
      and that avoidance inclinations were uniquely related to taking steps to make a
      change in alcohol use at baseline. In addition, avoidance inclinations were
      positively associated with number of sessions attended with no association found
      for approach ratings. Finally, results suggested that changes observed in
      drinking outcomes (drinks/day and% days abstinent) were significantly associated
      with changes in approach, but not avoidance inclinations. CONCLUSIONS: These
      findings highlight the importance of measuring both desire to consume and desire
      to avoid consuming alcohol simultaneously and suggest that avoidance inclinations
      are associated with treatment initiation and retention, and approach inclinations
      with positive treatment outcomes.

PMID- 22459328
TI  - Glycerol as a sole carbon source for enhanced biological phosphorus removal.
AB  - Wastewaters with low organic matter content are one of the major causes of EBPR
      failures in full-scale WWTP. This carbon source deficit can be solved by external
      carbon addition and glycerol is a perfect candidate since it is nowadays obtained
      in excess from biodiesel production. This work shows for the first time that
      glycerol-driven EBPR with a single-sludge SBR configuration is feasible (i.e.
      anaerobic glycerol degradation linked to P release and aerobic P uptake). Two
      different strategies were studied: direct replacement of the usual carbon source
      for glycerol and a two-step consortium development with glycerol anaerobic
      degraders and PAO. The first strategy provided the best results. The
      implementation of glycerol as external carbon source in full-scale WWTP would
      require a suitable anaerobic hydraulic retention time. An example using dairy
      wastewater with a low COD/P ratio confirms the feasibility of using glycerol as
      an external carbon source to increase P removal activity. The approach used in
      this work opens a new range of possibilities and, similarly, other fermentable
      substrates can be used as electron donors for EBPR.

PMID- 22459329
TI  - Potential source contributions and risk assessment of PAHs in sediments from
      Taihu Lake, China: comparison of three receptor models.
AB  - In this work, three receptor models (Principal Component Analysis-Multiple Linear
      Regression (PCA-MLR) model, Unmix model and Positive Matrix Factorization (PMF)
      model) were employed to investigate potential source apportionment of PAHs in
      sediments from Taihu Lake, China. A total of 15 priority PAHs in 29 sediments
      from Taihu Lake were measured, with ?PAHs (sum of 15 PAHs) concentrations ranging
      from 209 to 1003 ng g(-1) dw. Source apportionment results derived from three
      different models were similar, indicating that the highest contribution to ?PAHs
      was from vehicular emission (53.6-54.3%), followed by coal combustion (23.8
      28.8%) and wood combustion (11.9-16.0%). The contribution of mixed wood and coal
      combustion source identified by PCA-MLR was 41.3%. For the first time the risk
      assessment for each identified source category was quantitatively calculated by
      combining the BaP equivalents (BaPE) values with estimated source contributions.
      The results showed that vehicular emission posed the highest toxic risk, with
      BaPE values of 26.9-31.5 ng g(-1) dw, and the BaPE values for coal combustion and
      wood combustion were 6.56-15.6 ng g(-1) dw and 2.94-6.11 ng g(-1) dw,
      respectively. The distributions of contribution and BaPE for each identified
      source category were studied as well, and showed similar trends among the
      sampling sites, for each source category.

PMID- 22459330
TI  - The venom of the spider Macrothele raveni induces apoptosis in the myelogenous
      leukemia K562 cell line.
AB  - Spider venoms are a rich source of bioactive compounds with therapeutic
      potential. In traditional Chinese medicine, spiders and spider venoms have been
      used in the treatment of various ailments. In the present study, the venom of the
      spider Macrothele raveni potently suppressed cell growth in the myelogenous
      leukemia K562 cell line in a dose and time-dependent manner with an IC(50) of 5.1
      MUg/mL. The venom also had a low inhibitory effect on human lymphocytes with an
      IC(50) of approximately 36.4 MUg/mL, indicating that the venom is relatively
      selective for leukemic cells. Venom treated K562 cells showed typical
      morphological indicators of apoptosis including condensation of nuclei and
      fragmentation of DNA. Annexin V-FITC and propidium iodide dual staining further
      demonstrated that the venom had potent apoptogenic activity. Venom treatment
      induced caspase 3 and caspase 8 activation in K562 cells and promoted PARP
      cleavage. The present results indicate that the venom of the spider M. raveni
      potently and selectively suppresses the growth of K562 cells by inducing
      apoptosis via caspase 3 and caspase 8 mediated signaling pathways.

PMID- 22459331
TI  - Adherence to treatment is a complex and multifaceted issue that can substantially
      alter the outcome of chronic myeloid leukemia patients treated with tyrosine
      kinase inhibitors.

PMID- 22459332
TI  - Evolution of clinical trial endpoints in chronic myeloid leukemia: efficacious
      therapies require sensitive monitoring techniques.
AB  - The efficacy of tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia
      (CML) has brought treatment response assessment to the molecular level. Clinical
      trials endpoints for newer TKIs - such as major and complete molecular response -
      reflect the trend toward more-sensitive disease detection and deeper responses.
      Practice guidelines now formally define levels of response and link response
      benchmarks to outcome and treatment guidance. Efforts are ongoing to harmonize
      the methodology and terminology used to characterize molecular response. This
      review discusses the evolution of CML clinical trial endpoints in response to
      current therapeutic and monitoring modalities, and the implications of achieving
      molecular endpoints.

PMID- 22459333
TI  - Advanced systemic mastocytosis as a mimicker of metastatic clear cell renal cell
      carcinoma.

PMID- 22459334
TI  - Rotational catalysis in proton pumping ATPases: from E. coli F-ATPase to
      mammalian V-ATPase.
AB  - We focus on the rotational catalysis of Escherichia coli F-ATPase (ATP synthase,
      F(O)F(1)). Using a probe with low viscous drag, we found stochastic fluctuation
      of the rotation rates, a flat energy pathway, and contribution of an inhibited
      state to the overall behavior of the enzyme. Mutational analyses revealed the
      importance of the interactions among beta and gamma subunits and the beta subunit
      catalytic domain. We also discuss the V-ATPase, which has different physiological
      roles from the F-ATPase, but is structurally and mechanistically similar. We
      review the rotation, diversity of subunits, and the regulatory mechanism of
      reversible subunit dissociation/assembly of Saccharomyces cerevisiae and
      mammalian complexes. This article is part of a Special Issue entitled: 17th
      European Bioenergetics Conference (EBEC 2012).

PMID- 22459335
TI  - Can crossover and maximal fat oxidation rate points be used equally for
      ergocycling and walking/running on a track?
AB  - AIM: To verify whether exercise intensities at the crossover point (COP) and
      maximal lipid oxidation (Lipox(max)) can be used interchangeably regardless of
      exercise mode, this study compared COP, Lipox(max) and maximal fat oxidation rate
      (MFO) obtained during two modes of submaximal metabolic exercise tests:
      stationary cycling under laboratory conditions and walking/running on a track.
      METHODS: After preliminary indirect maximal progressive tests, 15 healthy
      subjects randomly performed submaximal exercise tests on a stationary cycle
      ergometer (E) and on a track (T), during which gas exchanges and substrate
      oxidation rates were measured. RESULTS: There were no significant mean
      differences in COP [heart rate (HR): 149+/-23 beats.min(-1) (T), 145+/-28
      beats.min(-1) (E); VO(2): 2168+/-896 mL.min(-1) (T), 2052+/-714 mL.min(-1) (E)],
      Lipox(max) [HR: 127+/-27 beats.min(-1) (T), 126+/-23 beats.min(-1) (E); VO(2):
      1638+/-839 mL.min(-1) (T), 1696+/-656 mL.min(-1) (E)] or MFO [498.3+/-192.0
      mg.min(-1) (T), 477.7+/-221.5 mg.min(-1) (E)] between the two modes of exercise.
      However, Bland-Altman analysis showed a clear disagreement between the two
      exercise modes and, in particular, a large random error [bias+/-random error: for
      COP, -3.5+/-53.2 beats.min(-1) (HR), -116.8+/-1556.4 mL.min(-1) (VO(2)); for
      Lipox(max), -0.4+/-43.3 beats.min(-1) (HR), -5.7+/-1286.4 mL.min(-1) (VO(2)); and
      for MFO, -20.6+/-384.9 mg.min(-1)]. CONCLUSION: This study showed that, in young,
      healthy, reasonably fit subjects, exercise mode can affect intensities at the COP
      and the Lipox(max). These results, which now have to be confirmed in patients
      with metabolic defects, suggest the need to perform specific tests to make
      individualized adaptations to physical activity outside of clinical settings.

PMID- 22459336
TI  - A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a
      bone-seeking radiopharmaceutical.
AB  - INTRODUCTION: The therapeutic potential of the bone-seeking radiopharmaceutical
      153Sm-labeled 1,4,7,10-tetraazacyclododecanetetramethylenephosphonic acid (153Sm
      DOTMP) was assessed by measuring its dosage-dependent skeletal uptake at two
      chelant-to-metal ratios and its source organ residence times at a chelant-to
      metal ratio of 1.5:1. A similar agent, 153Sm-labeled
      ethylenediaminetetramethylenephosphonic acid (153Sm-EDTMP), has been reported to
      exhibit dosage-limiting skeletal saturation. METHODS: Sm-DOTMP was prepared with
      tracer activity of 153Sm and sufficient stable, unenriched Sm to simulate
      different activities. Cohorts of seven 280-g Sprague-Dawley rats were
      administered the equivalent of 296, 592, 888, 1184 and 1480 MBq (8, 16, 24, 32
      and 40 mCi) at a fixed chelant-to-metal ratio of 1.5:1 and euthanized 3 h after
      administration. Cohorts of three 128-g Sprague-Dawley rats were administered
      equivalent dosages of 10.4, 592 and 888 (0.28, 16 and 32 mCi) at a fixed chelant
      to-metal ratio of 270:1 and euthanized 2 h after administration. A simulated
      activity of 1480 MBq (40 mCi) at a chelant-to-metal ratio of 1.5:1 was
      administered to cohorts of seven rats that were euthanized at 2, 4, 24 or 48 h
      postadministration. The heart, lungs, liver, spleen, kidneys, small intestine,
      large intestine, urinary bladder, muscle and a femur were excised, weighed and
      counted. The data were analyzed to determine skeletal uptake and source organ
      residence times. RESULTS: No statistically significant skeletal saturation was
      observed up to human-equivalent dosages of 370 GBq (10 Ci) at a chelant-to-metal
      ratio of 1.5:1, but the skeletal uptake dropped by 40% over the range of dosages
      at a chelant-to-metal ratio of 270:1. At a chelant-to-metal ratio of 1.5:1, the
      preferred ratio, the skeletal uptake fraction in rats was 0.408 (95% confidence
      interval 0.396-0.419) with an effective half-life of 47.3 h (95% confidence
      interval 42.3-53.7; the physical half-life of 153Sm is 46.3 h). Extrapolating to
      an adult human model, 52.9 GBq (1.43 Ci) of 153Sm-DOTMP would deliver 40 Gy to
      the red marrow. CONCLUSION: 153Sm-DOTMP has dosimetry equivalent to that of 153Sm
      EDTMP at low dosages, yet with no skeletal saturation at higher administered
      activities.

PMID- 22459338
TI  - Moral decision-making, ToM, empathy and the default mode network.
AB  - Automatic intuitions and deliberate reasoning, sourcing internal representations
      of our personal norms and values, contribute to our beliefs of what is right and
      wrong. We used fMRI to directly compare moral (M) and non-moral (NM) decision
      making processes using scenarios requiring conscious deliberation, whereby the
      main character declared an intention to take a course of action. Furthermore, we
      examined the relationship between BOLD signal, associated with M>NM decision
      making, and moral judgment competence, psychopathy, and empathy. We observed
      greater activity in various parts of Theory of Mind, empathy and default mode
      networks during M>NM decision-making. There was a trend for high scores on
      primary psychopathy to correlate with decreased M>NM BOLD activation in an area
      extending from dorsolateral prefrontal cortex to medial prefrontal cortex. We
      suggest that moral decision-making entails a greater degree of internally
      directed processing, such as self-referential mental processing and the
      representation of intentions and feelings, than non-moral decision-making.

PMID- 22459337
TI  - Preliminary studies on (177)Lu-labeled sodium pyrophosphate (177Lu-PYP) as a
      potential bone-seeking radiopharmaceutical for bone pain palliation.
AB  - OBJECTIVE: (99m)Tc-Sn-PYP (Technetium-99(m) labeled tin pyrophosphate) has been
      widely used as a radiopharmaceutical for bone scanning as well as in nuclear
      cardiology. It is also found in the body in trace amounts. (177)Lu is presently
      considered as an excellent radionuclide for developing bone pain palliation
      agents. PYP is an analogue of MDP and MDP has been labeled with (177)Lu. No study
      on preparing a complex of (177)Lu with PYP has been reported yet. Based on these
      facts, it was hypothesized that a bone-seeking (177)Lu-PYP (Lutetium-177 labeled
      Pyrophosphate) radiopharmaceutical could be developed as an agent for palliative
      radiotherapy of bone pain due to skeletal metastases. METHODS: (177)Lu was
      produced by irradiating lutetium foil (11 mg) natural target at a flux
      ~1.0*10(14)n/cm(2)/s for 12 h in the swimming pool type reactor. (177)Lu in the
      form of (177)LuCl(3) was labeled with PYP. The radiochemical purity and labeling
      efficiencies were determined by paper chromatography. Labeling of (177)Lu with
      PYP was optimized and a labeled sample was subjected to HPLC analysis. To
      determine the charge on the (177)Lu-PYP complex, radio-electrophoresis was
      conducted for 1 h under a voltage of 300 V and 45 mA current using 0.025 M
      phosphate buffer (pH 6.9). Bioevaluation studies with rabbit under gamma-camera
      were also performed to verify the skeletal uptake. RESULTS: The quality control
      using paper radio-chromatography has shown >99% radiochemical purity of (177)Lu
      PYP complex. Radio-chromatography also showed maximum labeling at ligand/metal
      ratio=60:1. HPLC analysis showed 1.42+/-0.01 min retention time of (177)Lu-PYP
      complex. No decrease in labeling was observed at higher temperatures. Gamma
      camera images of (177)Lu-PYP in normal rabbit at 24 h post injection also showed
      high skeletal uptake. CONCLUSION: The study demonstrated that sodium
      pyrophosphate could be labeled with (177)Lu with high radiochemical yields
      (>99%). Negatively charged (177)Lu-PYP complex retained stability for a day and
      at high temperatures too. Gamma-camera images of (177)Lu-PYP in normal rabbit at
      24 h post injection showed high skeletal uptake, suggesting that it may be useful
      as a bone-pain palliation agent for the treatment of bone metastases.

PMID- 22459339
TI  - Ophthalmic regional blockade complication rate: a single center audit of 33,363
      ophthalmic operations.
AB  - STUDY OBJECTIVE: To determine the incidence and contributing factors of
      complications for patients receiving regional ophthalmic anesthesia. DESIGN:
      Retrospective analysis. SETTING: Tertiary-care eye center. MEASUREMENTS:
      Anesthesia records of ophthalmic blocks performed from January 2003 to June 2009
      were reviewed. The frequency of block-related complications and details of each
      complication were recorded. MAIN RESULTS: A total of 33,363 peribulbar blocks
      were performed, with a total incidence of 0.12% (41 cases). These complications
      may be divided into systemic complications, 18 cases (0.053%) and needle-related
      complications, 23 cases (0.068%). CONCLUSION: Peribulbar block complications were
      rare. In this series, experience of caregivers and axial and needle length were
      not contributing factors.

PMID- 22459340
TI  - Influence of the menstrual cycle on the incidence of nausea and vomiting after
      laparoscopic gynecological surgery: a pilot study.
AB  - STUDY OBJECTIVE: To investigate whether the phase of menstrual cycle influences
      the incidence of postoperative nausea and vomiting (PONV) in women undergoing
      general anesthesia for elective laparoscopic gynecological surgery. DESIGN:
      Prospective, observational, blinded study. SETTING: General hospital,
      Postanesthesia Care Unit, and gynecologic floor room. PATIENTS: 111 ASA physical
      status 1 and 2 women, aged 18 to 53 years. INTERVENTIONS: Patients were
      classified into three groups according to the phase of menstrual cycle at the
      time of anesthesia: Group F1: follicular phase (menstrual days 1-8; n = 34);
      Group O2: ovulatory phase (days 9-15; n = 40); and Group L3: luteal phase (days
      16 to end of cycle; n = 37). Anesthetic, postoperative pain management, and
      antiemetic regimens were standardized. MEASUREMENTS: Frequency of nausea,
      vomiting, or both were assessed for early (0-2 hrs). Late PONV (2-24 hrs) along
      with the use of rescue antiemetic, severity of nausea, and pain. MAIN RESULTS: In
      the follicular (n = 34), ovulatory (n = 40) and luteal phase (n = 37) groups, the
      frequencies of PONV over 24 hours were 35%, 38%, and 14% (P = 0.04),
      respectively. This was due to differences in the early postoperative period where
      the frequencies were 21%, 25%, and 3% (P = 0.02), respectively, as frequencies
      were similar in the late period (15%, 20% and 14%, P = 0.71), respectively.
      Nausea scores, rescue antiemetic usage, pain scores, and opioid consumption were
      similar in the groups. CONCLUSION: Patients in the luteal phase of their
      menstrual cycle may have a decreased risk of PONV after laparoscopic
      gynecological surgery in the early postoperative period.

PMID- 22459341
TI  - A randomized, placebo-controlled study of pregabalin for postoperative pain
      intensity after laparoscopic cholecystectomy.
AB  - STUDY OBJECTIVE: To determine the efficacy of two different doses (150 mg and 300
      mg) of preoperative pregabalin on pain relief and total opioid consumption after
      laparoscopic cholecystectomy. DESIGN: Prospective, randomized, placebo
      controlled, double-blinded study. SETTING: Training and research hospital.
      PATIENTS: 90 adult, ASA physical status 1 and 2 patients. INTERVENTIONS: Patients
      were randomly assigned to three groups to receive orally one hour before surgery,
      a placebo (Group 1), pregabalin 150 mg (Group 2), or pregabalin 300 mg (Group 3).
      Patients were observed for pregabalin side effects, somnolence via Ramsay
      Sedation Scale, dizziness, confusion, and ataxia. MEASUREMENTS: In the operating
      room, heart rate and noninvasive systolic and diastolic blood pressures were
      measured. Visual analog scale (VAS), Ramsay Sedation Scale, and Aldrete scores
      were also recorded on arrival at the Postanesthesia Care Unit (time 0), 15, 30,
      60, 120 minutes and 3, 4, 6, 8, 10, 12 and 24 hours after surgery. Additional
      doses of drugs (fentanyl and/or metoclopramide) were also recorded. MAIN RESULTS:
      Preemptive pregabalin decreased pain scores and postoperative fentanyl
      consumption in patients after laparoscopic cholecystectomy in a dose-dependent
      manner. There were no differences between the groups in side effects. CONCLUSION:
      Preoperative pregabalin may be a useful analgesic for patients after laparoscopic
      cholecystectomy, as it lowers pain intensity and opiod consumption, and does not
      increase the frequency of side effects.

PMID- 22459342
TI  - The use of multiple endpoints to assess cellular responses to environmental
      contaminants in the interstitial marine ciliate Euplotes crassus.
AB  - This paper presents the results of investigations on the suitability of Euplotes
      crassus, an interstitial marine ciliate, to be used as model organism in
      ecotoxicology and thereafter to evaluate the toxicity of estuarine and coastal
      sediments upon laboratory exposure. Nowadays, anthropogenic activities have
      resulted in accumulation of metals and organic pollutants in the environment as
      well as in the food chain hence leading to serious ecological and human health
      problems. This may pose a risk to benthic and epibenthic organisms and it is
      crucial to discover toxicity tests that will identify adverse effects of sediment
      associated chemicals on benthic organisms. Due to their nature as a eukaryotic
      cell/organism and their position in the food web, ciliated protozoa are suitable
      models for evaluating the effects of pollution on aquatic communities. Lethal and
      sublethal effects of exposure to inorganic and organic pollutants were tested on
      the cell mortality, replication rate, lysosomal membrane stability and
      endocytosis rate of E. crassus. Increasing nominal concentrations of individual
      and mixtures of mercury, copper, and benzo(a)pyrene were investigated in this
      study as they might be bioavailable in naturally occurring polluted sites. A
      significant decrease in the mean replication rate (p<0.05) was found after 24h
      exposures to m/MUM concentrations of all tested pollutants. At the same time,
      significant decreases of lysosomal membrane stability (p<0.05) were observed for
      Cu (5 MUM), Hg (10 nM), and B(a)P (200 nM). Among the entire suite of tests,
      endocytosis rate test demonstrated the highest sensitivity. Exposures to binary
      mixtures of all studied pollutants were performed showing both inorganic-organic
      and inorganic-inorganic additive and/or antagonist effects. Moreover, medium
      salinity was also varied to mimic estuarine-like environmental conditions linking
      biological response to ionic strengths. Under these conditions significant
      increases of both endocytosis rate and lysosomal membrane stability were observed
      and related to the increment of some Hg- and Cu-related toxic complexes. The
      studied biomarkers were always able to discriminate between the effects of
      organic and inorganic pollutants. Together with the short time and simplicity of
      the test procedures, results obtained in this study indicate that E. crassus is a
      promising and convenient bioindicator for evaluating the toxicity of different
      environmental matrixes like pore water, sediments and wastewaters--polluted by
      metals and organic pollutants.

PMID- 22459343
TI  - In vivo biodegradation of colloidal quantum dots by a freshwater invertebrate,
      Daphnia magna.
AB  - Impacts of planktonic invertebrate, Daphnia magna, on the speciation of colloidal
      quantum dots (QD) were investigated using fluorescence spectromicroscopic
      technique. Well-dispersed (GA/TOPO)QD were prepared by forming a supramolecular
      assembly of hydrophobic (TOPO)QD with biomacromolecules (i.e., Gum Arabic, GA).
      Biological degradation of this nanomaterial was monitored by fluorescence
      spectromicroscopic methods. Our study confirmed the major uptake pathway of
      manufactured nanomaterials and in vivo biodegradation processes in a well-known
      toxicity test organism, D. magna. In addition, we also found that D. magna can
      induce significant deterioration of aquatic media by releasing fragments of
      partially degraded QD colloids. These biological processes may significantly
      change the predicted toxicities of nanomaterials in aquatic environments. Thus,
      we propose that the impacts of aquatic living organisms on the environmental fate
      of manufactured nanomaterials (MNs) should be carefully taken into account when
      assessing the risk of MNs to the environment and human health.

PMID- 22459344
TI  - Reply: To PMID 22405526.

PMID- 22459345
TI  - Electrosurgery research.

PMID- 22459346
TI  - Diagnostic accuracy of visual urethral mobility exam versus Q-Tip test: a
      randomized crossover trial.
AB  - OBJECTIVE: The objective of the study was to compare the diagnostic accuracy of a
      visual urethral mobility examination (VUME) with a Q-Tip test in the assessment
      of urethral hypermobility. STUDY DESIGN: Subjects were randomized to a VUME or Q
      Tip test first, followed by the alternate assessment. Outcomes included
      hypermobile, not hypermobile, or indeterminate. Hypermobility was defined as 30
      degrees  or greater from the horizontal. Pain perception and test preference were
      assessed. RESULTS: For the 54 subjects, 61.1% demonstrated hypermobility on VUME
      vs 72.2% on the Q-Tip test (P = .39). Assessment of hypermobility was correlated
      between the 2 tools (rho = 0.47, P = .001). Positive and negative predictive
      value, sensitivity, and specificity for VUME were 88%, 56%, 78%, and 71%,
      respectively, with a Q-Tip test as the reference standard. Mean pain score on
      visual analog scale was 0.72 for VUME and 3.15 for Q-tip test (P < .001). VUME
      was preferred by 83% of subjects. CONCLUSION: VUME is a diagnostic alternative to
      the Q-Tip test for the assessment of urethral hypermobility and is preferred by
      subjects.

PMID- 22459347
TI  - Intermodality comparison between 3D perfusion CT and 18F-FDG PET/CT imaging for
      predicting early tumor response in patients with liver metastasis after
      chemotherapy: preliminary results of a prospective study.
AB  - OBJECTIVES: To evaluate the feasibility of 3D perfusion CT for predicting early
      treatment response in patients with liver metastasis from colorectal cancer.
      METHODS: Seventeen patients with colon cancer and liver metastasis were
      prospectively enroled to undergo perfusion CT and 18F-FDG-PET/CT before and after
      one-cycle of chemotherapy. Two radiologists and three nuclear medicine physicians
      measured various perfusion CT and PET/CT parameters, respectively from the
      largest hepatic metastasis. Baseline values and reduction rates of the parameters
      were compared between responders and nonresponders. Spearman correlation test was
      used to correlate perfusion CT and PET/CT parameters, using RECIST criteria as
      reference standard. RESULTS: Nine patients responded to treatment, eight patients
      were nonresponders. Baseline SUVmean30 on PET/CT, reduction rates of 30%
      metabolic volume and 30% lesion glycolysis (LG30) on PET/CT and blood flow (BF)
      and flow extraction product (FEP) on perfusion CT after chemotherapy were
      significantly different between responders and nonresponders (P=0.008-0.046).
      Reduction rates of BF (correlation coefficient=0.630) and FEP (correlation
      coefficient=0.578) significantly correlated with that of LG30 on PET/CT (P<0.05).
      CONCLUSION: CT perfusion parameters including BF and FEP may be used as early
      predictors of tumor response in patients with liver metastasis from colorectal
      cancer.

PMID- 22459348
TI  - Time-resolved CT angiography in aortic dissection.
AB  - OBJECTIVES: We performed this study to assess feasibility and additional
      diagnostic value of time-resolved CT angiography of the entire aorta in patients
      with aortic dissection. MATERIALS AND METHODS: 14 consecutive patients with known
      or suspected aortic dissection (aged 60+/-9 years) referred for aortic CT
      angiography were scanned on a dual-source CT scanner (Somatom Definition Flash;
      Siemens, Forchheim, Germany) using a shuttle mode for multiphasic image
      acquisition (range 48 cm, time resolution 6s, 6 phases, 100 kV, 110 mAs/rot).
      Effective radiation doses were calculated from recorded dose length products. For
      all phases, CT densities were measured in the aortic lumen and renal parenchyma.
      From the multiphasic data, 3 phases corresponding to a triphasic standard CT
      protocol, served as a reference and were compared against findings from the time
      resolved datasets. RESULTS: Mean effective radiation dose was 27.7+/-3.5 mSv. CT
      density of the true lumen peaked at 355+/-53 HU. Compared to the simulated
      triphasic protocol, time-resolved CT angiography added diagnostic information
      regarding a number of important findings: the enhancement delay between true and
      false lumen (n=14); the degree of membrane oscillation (n=14); the perfusion
      delay in arteries originating from the false lumen (n=9). Other additional
      information included true lumen collapse (n=4), quantitative assessment of renal
      perfusion asymmetry (n=2), and dynamic occlusion of aortic branches (n=2). In
      3/14 patients (21%), these additional findings of the multiphasic protocol
      altered patient management. CONCLUSIONS: Multiphasic, time-resolved CT
      angiography covering the entire aorta is feasible at a reasonable effective
      radiation dose and adds significant diagnostic information with therapeutic
      consequences in patients with aortic dissection.

PMID- 22459349
TI  - Targeting a cornerstone of radiation resistance: cancer stem cell.
AB  - In radiation oncology, cancer stem cells (CSCs) have become an important research
      field. In fact, it appears that most cancer types contain populations of cells
      that exhibit stem-cell properties. CSCs have the ability to renew indefinitely,
      which can drive tumor development and metastatic invasion. As those cells are
      classically resistant to conventional chemotherapy and to radiation therapy, they
      may contribute to treatment failure and relapse. Over past decades, preclinical
      research has highlighted that variations in the CSCs content within tumor could
      affect their radiocurability by interfering with mechanisms of DNA repair,
      redistribution in the cell cycle, tumor cells repopulation, and hypoxia. It is
      now possible to isolate particular cells expressing specific surface markers and
      thus better investigating CSCs pathways. Numerous inhibitory agents targeting
      these specific signaling pathways, such as Notch and Wnt/B-catenin, are currently
      evaluated in early clinical trials. By targeting CSCs, tumor radioresistance
      could be potentially overcome to improve outcome for patients with solid
      malignancies. Radiation therapy using ion particles (proton and carbon) may be
      also more effective than classic photon on CSCs. This review presents the major
      pathophysiological mechanisms involved in CSCs radioresistance and recent
      developments for targeted strategies.

PMID- 22459350
TI  - Sphere formation reverses the metastatic and cancer stem cell phenotype of the
      murine mammary tumour 4T1, independently of the putative cancer stem cell marker
      Sca-1.
AB  - Breast cancer stem cells (BCSCs) initiate and sustain breast cancers, and several
      putative markers have been proposed to prospectively isolate BCSC from the non
      cancer stem cell population. The candidate BCSC marker Sca-1 is a GPI-linked
      membrane protein expressed on activated lymphocytes, hematopoietic stem cells and
      mammary stem cells. Sca-1+ cells were purified from the murine mammary tumour
      cell line 4T1. However, this did not enrich for a stem-like, tumour initiating or
      metastatic cell population in vitro or in vivo. Sphere formation, which induced
      high levels of Sca-1, reduced BCSC gene expression with near complete loss of
      spontaneous metastasis from sphere-derived tumours. This was associated with
      decreased expression of TGFB2 and reduced activation of the TGFbeta signalling
      pathway in spheres. Both TGFB2 expression in vitro and spontaneous metastasis in
      vivo could be restored upon re-differentiation of sphere cells by exposure to
      serum, and this occurred with retention of the majority of Sca-1 expression. We
      conclude that while putative BCSC, including spheres, can have high Sca-1
      expression, Sca-1 itself is not a marker of BCSC in established 4T1 tumours or
      the cell line.

PMID- 22459351
TI  - Insulin promotes proliferation, survival, and invasion in endometrial carcinoma
      by activating the MEK/ERK pathway.
AB  - The involvement of insulin in endometrial carcinoma (EC) was investigated using
      radioimmunoassay, Western blot, immunoprecipitation, MTT, and Annexin V-FITC/PI
      assays in tissue samples and cultured cells. Serum levels of insulin, p-p52Shc, p
      p46Shc, Shc.Grb2 complexes, p-MEK, p-ERK, and cyclin D1 were elevated in patients
      with EC. Expression of key proteins in the MEK/ERK pathway, including p-p52Shc,
      Shc.Grb2 complexes, p-MEK, p-ERK, and cyclin D1, was significantly higher in
      patients with advanced FIGO stage, high grade, and lymph-node metastasis and
      correlated positively with serum insulin concentration. Insulin promotes Ishikawa
      3-H-12 cell proliferation, survival, and invasion, and these effects induced by
      insulin were significantly blocked by MEK inhibitor PD98059. Insulin thus
      promotes EC cell proliferation, survival, and invasion via the MEK/ERK pathway.

PMID- 22459352
TI  - Over-expression of MAGED4B increases cell migration and growth in oral squamous
      cell carcinoma and is associated with poor disease outcome.
AB  - MAGE proteins have been shown to be good targets for cancer immunotherapy. We
      demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell
      Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph
      node metastasis and poor disease specific survival. OSCC cell lines that over
      express MAGED4B promote migration in vitro, exhibit an increase in cell growth
      both in vitro and in vivo, and are more resistant to apoptosis compared to
      control cells. Our data suggest that MAGED4B over-expression is a driver in oral
      carcinogenesis and argues strongly that this protein may represent a potential
      therapeutic target in OSCC.

PMID- 22459353
TI  - Human gastric cancer development with TNF-alpha-inducing protein secreted from
      Helicobacter pylori.
AB  - TNF-alpha-inducing protein (Tipalpha) is a unique carcinogenic factor of
      Helicobacter pylori, which is secreted into culture broth. The biological
      activities of Tipalpha and deletion mutant were studied. Tipalpha protein
      specifically binds to cell-surface nucleolin and then enters the gastric cancer
      cells, where TNF-alpha and chemokine gene expressions are induced by NF-kappaB
      activation. Nucleolin localizes on the surface of gastric cancer cells, and
      interaction between Tipalpha and cell-surface nucleolin causes a cancer-oriented
      microenvironment that increases the risk of gastric cancer. This paper discusses
      a new mechanism of gastric cancer development with H. pylori and provides a new
      preventive strategy.

PMID- 22459354
TI  - Two sons and a daughter: sex composition and women's reproductive behaviour in
      Madhya Pradesh, India.
AB  - This article examines how the sex composition of women's current children at the
      start of a pregnancy interval influences both fertility desires and the full
      range of reproductive actions women may take to realize them, including temporary
      contraception, abortion and sterilization, in Madhya Pradesh, India, where
      popular notions of ideal family size and sex composition are dominated by son
      preference. The analysis is conducted using a dataset of 9127 individual
      pregnancy intervals from a 2002 statewide representative survey of 2444 women
      aged 15-39 with at least one child. The results indicate that women's preferences
      go beyond a singular preference for male children, with the preferred composition
      of children being two boys and one girl. Women with this composition are 90% less
      likely to report having wanted another pregnancy (OR 0.097, p < 0.01) relative to
      those with two girls. These preferences have significant implications for
      reproductive actions. While sex composition has no statistically significant
      effect on the use of temporary contraception, those with the preferred sex
      composition are twice as likely to attempt abortion (OR 2.436, p < 0.01) and
      twelve times more likely to be sterilized (OR 12.297, p < 0.01) relative to those
      with two girls only.

PMID- 22459355
TI  - N-methyl D-aspartate receptor antibody encephalitis associated with myelitis.
AB  - Encephalitis associated with antibodies to the N-methyl D-aspartate receptor
      (NMDA-R) was first described in young women with ovarian teratoma. It has
      subsequently been described in men, children and in those without an underlying
      tumour. Characteristic clinical features include neuropsychiatric symptoms,
      seizures, movement disorders, hypoventilation and autonomic instability. Spinal
      cord disease in association with other typical clinical features has been
      described in only one patient previously. We report a patient presenting with
      myelitis, with typical features of NMDA-R associated encephalitis manifesting 3
      months later.

PMID- 22459356
TI  - Oral contraceptive use and clinical outcomes in patients with multiple sclerosis.
AB  - Experimental and clinical data suggest a role of sex steroids in the pathogenesis
      of multiple sclerosis (MS). Scant information is available about the potential
      effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed
      to evaluate this. The study population consisted of 132 women with relapsing
      remitting MS before receiving disease modifying treatment and a mean disease
      duration 6.2 (SD 5.1) years. Three groups of patients were distinguished
      according to their OC behavior: [1] never-users, patients who never used OC [2]
      past-users, patients who stopped OC use before disease onset, and [3] after
      users, those who used these drugs after disease onset. Multiple linear and
      logistic regression models were used to analyze the association between oral
      contraceptive use and annualized relapse rates, disability accumulation and
      severity of the disease. After-user patients had lower Expanded Disability Status
      Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users
      (p<0.001 and p=0.002, respectively) and past users (p=0.010 and p=0.002,
      respectively). These patients were also more likely to have a benign disease
      course (MSSS<2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56,
      p<0.001). This effect remained significant after adjustment for confounders,
      including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p=0.011 and for
      MSSS beta: -1.04; 95% C.I. -1.78, -0.30, p=0.006). These results suggest that OC
      use in women with relapsing-remitting MS is possible associated with a milder
      disabling disease course.

PMID- 22459358
TI  - Mesenchymal stem cells: therapeutic outlook for stroke.
AB  - Adult bone marrow-derived mesenchymal stem cells (MSCs) display a spectrum of
      functional properties. Transplantation of these cells improves clinical outcome
      in models of cerebral ischemia and spinal cord injury via mechanisms that may
      include replacement of damaged cells, neuroprotective effects, induction of
      axonal sprouting, and neovascularization. Therapeutic effects have been reported
      in animal models of stroke after intravenous delivery of MSCs, including those
      derived from adult human bone marrow. Initial clinical studies on intravenously
      delivered MSCs have now been completed in human subjects with stroke. Here, we
      review the reparative and protective properties of transplanted MSCs in stroke
      models, describe initial human studies on intravenous MSC delivery in stroke, and
      provide a perspective on prospects for future progress with MSCs.

PMID- 22459357
TI  - Tunicamycin produces TDP-43 cytoplasmic inclusions in cultured brain organotypic
      slices.
AB  - The cellular distribution of TAR DNA binding protein (TDP-43) is disrupted in
      several neurodegenerative disorders, including frontotemporal lobar degeneration
      with ubiquitin-positive inclusions (FTLD-U subtype) and amyotrophic lateral
      sclerosis (ALS). In these conditions, TDP-43 is found in neuronal cytoplasmic
      inclusions, with loss of the normal nuclear expression. The mechanisms leading to
      TDP-43 redistribution and its role in disease pathophysiology remain unknown. We
      describe an in vitro neural tissue model that reproduces TDP-43 relocalization
      and inclusion formation. Two week-old coronal organotypic mouse brain slice
      cultures were treated with tunicamycin for 7 days. In cortical regions of treated
      slice cultures, cytoplasmic inclusions of TDP-43 immunoreactivity were observed,
      with loss of nuclear TDP-43 immunoreactivity. These inclusions were found in both
      astrocytes and neurons, and were of both skein-like and round morphologies. In
      contrast, TDP-43 cytoplasmic inclusions were not found in slices treated with
      staurosporine to induce apoptosis, or with trans-4-carboxy-l-proline (PDC) to
      induce chronic glutamate excitotoxicity. Furthermore, TDP-43 cytoplasmic
      inclusions did not co-localize with cleaved caspase-3, suggesting that TDP-43
      mislocalization does not generally accompany caspase activation or apoptosis. The
      induction of TDP-43 cytoplasmic translocation in cerebrocortical slice cultures
      by tunicamycin provides a platform for further mechanistic investigations of
      pathological processing of TDP-43.

PMID- 22459359
TI  - Hypopigmented parapsoriasis en plaque, a new, overlooked member of the
      parapsoriasis family: a report of 34 patients and a 7-year experience.
AB  - BACKGROUND: In the past 7 years we have extensively studied an uncommon
      hypopigmented disorder that, apart from hypopigmentation, showed many common
      features with parapsoriasis en plaque (PSEP), both clinically and
      histopathologically. OBJECTIVE: We sought to verify whether this disorder should
      be considered a hypopigmented variant of PSEP and thus be referred to as
      hypopigmented PSEP. METHODS: A total of 34 patients presenting with this peculiar
      hypopigmented disorder were included (2003-2010). Patients were subjected to a
      predesigned algorithm excluding all possible differential diagnoses of
      hypopigmented lesions. RESULTS: Our findings indicated that this disorder can be
      diagnosed as hypopigmented PSEP. These findings included: (1) exclusion of all
      other disorders causing similar hypopigmented lesions; (2) shape and size of the
      lesions being very similar to those of classic small PSEP (small-plaque
      parapsoriasis [SPP]); (3) similar distribution of the lesions (trunk, proximal
      upper and lower limbs) to the classic PSEP; (4) digitiform extensions of most the
      lesions (70.5% of our patients) as in SPP; (5) absence of itching as in PSEP (SPP
      type); (6) good response to narrowband ultraviolet B in 76.4% of the patients (n
      = 26); and (7) during follow-up 5 patients (14.7%) converted into hypopigmentd
      mycosis fungoides. LIMITATIONS: A limitation in our study is that we did not
      perform clonal T-cell receptor gene rearrangement because of limited resources.
      CONCLUSION: Based on our findings we believe that this hypopigmented disorder is
      a well-defined new variant of the PSEP family that shows, apart from the
      hypopigmentation, all the features of PSEP, particularly the SPP variant, and
      accordingly could be referred to as hypopigmented PSEP.

PMID- 22459360
TI  - State of teledermatology programs in the United States.
AB  - BACKGROUND: Teledermatology programs in the United States have evolved over the
      past several decades. No systematic survey of teledermatology programs in the
      United States is available in peer-reviewed literature. OBJECTIVE: To provide up
      to-date information regarding the state of teledermatology programs in the United
      States. METHODS: Active U.S. teledermatology programs were surveyed in 2011 with
      regards to practice models, clinical volume, and payment methods. These findings
      were compared with those from 2003. RESULTS: By January 2012, 37 teledermatology
      programs were active in the United States. Store-and-forward teledermatology was
      the most frequent delivery modality offered by 30 (81%) of the programs. The
      majority of the programs were based at academic institutions (49%), followed by
      Veterans Administration hospitals (27%), private practice (16%), and health
      maintenance organizations (HMOs) (8%). The majority of programs (67%) provided
      services to their home state only, whereas the rest also served additional U.S.
      states or abroad. The median number of consultations per program was 309 (range,
      5-6500) in 2011. The most frequent payer sources were private payers, followed by
      self-pay, Medicaid, Medicare, and HMOs. Since 2003, with the confirmed
      discontinuation of 24 previously active programs, the total number of active
      teledermatology programs in 2011 was 60% of that in 2003. However, the annual
      consult volume per program nearly doubled for the sustainable programs in 2011.
      LIMITATIONS: Itemized billing information was not uniformly available from all
      programs. CONCLUSION: The turnover in teledermatology programs is relatively
      constant, with an increase in consult volume for sustainable programs. Store-and
      forward is the dominant modality of delivery, while hybrid technology model is
      emerging.

PMID- 22459361
TI  - A retrospective analysis of the Dermatology Foundation's Career Development Award
      Program.
AB  - BACKGROUND: To provide research support that develops and retains leaders,
      educators, and investigators in dermatology and cutaneous biology, the
      Dermatology Foundation (DF) has designed and implemented a comprehensive Career
      Development Award (CDA) Program. OBJECTIVE: To assess the impact of the DF's 3
      year CDA, a comprehensive survey of recipients who received this mechanism of
      support between 1990 and 2007 was performed. METHODS: Of 196 individuals
      receiving a DF CDA, 181 were identified and asked to complete a comprehensive
      questionnaire concerning their career status, employment history, professional
      rank, and record of independent research funding (private foundation, federal,
      other). A personal assessment of the impact of this funding on these individuals'
      career trajectory was also requested. RESULTS: Eighty percent of 181 CDA
      recipients identified currently hold full- or part-time positions in academic
      medicine. The faculty rank of 112 survey respondents included 46 assistant
      professors (41%), 41 associate professors (37%), 18 professors (16%), and 7
      division or departmental chairs (6%). Of respondents, 84% reported that they have
      received subsequent independent research funding; 95 of these individuals (86%)
      have received funding from a federal agency (235 federal grants awarded to date
      with funding >$318M). LIMITATIONS: The study was retrospective and self-reported;
      some awardees did not respond to the survey. CONCLUSIONS: The DF's CDA Program
      has succeeded in supporting the early career development of talented
      investigators, educators, and leaders; fostered the promotion and retention of
      these individuals in academic medicine; and nucleated numerous investigative
      careers that have successfully acquired independent research funding.

PMID- 22459362
TI  - Molecular biology of melanoma.
AB  - Dermatologists and dermatopathologists face the difficulties of accurately
      diagnosing and treating atypical melanocytic lesions and melanomas. Despite huge
      advances in medicine, our management of melanoma has not significantly changed in
      many years. The biggest gains made recently have been in the identification of
      common mutations in melanoma and the use of these mutations to aid in the
      diagnosis and treatment of melanoma. To understand these gains one must first be
      familiar with the regulatory pathways of melanoma and the most common mutations
      found there. This article will review the function and significance of the most
      studied mutations in melanoma and briefly discuss new and planned treatment
      options.

PMID- 22459363
TI  - Novel devices and specialized techniques in recanalization of peripheral artery
      chronic total occlusions (CTOs)--a literature review.
AB  - Currently, recanalization of chronic total occlusions (CTOs) in peripheral
      arteries remains a challenging obstacle encountered by clinical practitioners.
      Percutaneous CTO interventions are associated with low rates of procedural
      success using standard guidewires and catheters. When guidewires cannot cross the
      occluded segment or fail to reenter the true lumen after subintimal crossing of
      the occlusion, successful recanalization may be unachievable. In the last few
      years, the emergence of novel devices and new techniques has dramatically
      improved the success rates of the revascularization for CTOs. This paper reviews
      the published data of current devices and specialized techniques of percutaneous
      intervention to relieve CTOs.

PMID- 22459364
TI  - A systematic approach to designing reliable VV optimization methodology:
      assessment of internal validity of echocardiographic, electrocardiographic and
      haemodynamic optimization of cardiac resynchronization therapy.
AB  - BACKGROUND: In atrial fibrillation (AF), VV optimization of biventricular
      pacemakers can be examined in isolation. We used this approach to evaluate
      internal validity of three VV optimization methods by three criteria. METHODS AND
      RESULTS: Twenty patients (16 men, age 75 +/- 7) in AF were optimized, at two
      paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG
      (minimizing QRS duration). Each optimization method was evaluated for:
      singularity (unique peak of function), reproducibility of optimum, and biological
      plausibility of the distribution of optima. The reproducibility (standard
      deviation of the difference, SDD) of the optimal VV delay was 10 ms for pressure,
      versus 8 ms (p=ns) for QRS and 34 ms (p<0.01) for flow. Singularity of optimum
      was 85% for pressure, 63% for ECG and 45% for flow (Chi(2)=10.9, p<0.005). The
      distribution of pressure optima was biologically plausible, with 80% LV pre
      excited (p=0.007). The distributions of ECG (55% LV pre-excitation) and flow (45%
      LV pre-excitation) optima were no different to random (p=ns). The pressure
      derived optimal VV delay is unaffected by the paced rate: SDD between slow and
      fast heart rate is 9 ms, no different from the reproducibility SDD at both heart
      rates. CONCLUSIONS: Using non-invasive arterial pressure, VV delay optimization
      by parabolic fitting is achievable with good precision, satisfying all 3 criteria
      of internal validity. VV optimum is unaffected by heart rate. Neither QRS
      minimization nor LVOT VTI satisfy all validity criteria, and therefore seem
      weaker candidate modalities for VV optimization. AF, unlinking interventricular
      from atrioventricular delay, uniquely exposes resynchronization concepts to
      experimental scrutiny.

PMID- 22459365
TI  - Normalcy rate of computed tomographic coronary angiography.

PMID- 22459366
TI  - Impact of transcatheter aortic valve implantation with the CoreValve prosthesis
      in patients with severe aortic stenosis and left ventricular dysfunction.

PMID- 22459367
TI  - New strategy for a stumpless aorto-ostial chronic total occlusion.

PMID- 22459368
TI  - Relationship between Holter findings immediately after ablation of typical atrial
      flutter and subsequent risk of atrial fibrillation.

PMID- 22459369
TI  - Stent-anchored coil embolotherapy--novel treatment procedure for huge pulmonary
      arterio-venous malformation in hereditary hemorrhagic telangiectasia.

PMID- 22459370
TI  - Comparison of various methods for quantitative evaluation of myocardial infarct
      volume from magnetic resonance delayed enhancement data.
AB  - BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance
      (CMR) enables the estimation of myocardial infarct (MI) extent. Nevertheless,
      manual quantification is time consuming and subjective. We sought to assess MI
      volume with different quantitative methods in both acute (AMI) and chronic MI
      (CMI). METHODS: CMR was performed 50 +/- 21 h after MI in 52 patients and was
      repeated 100 +/- 21 days later in a subgroup of 34 patients. Then, necrosis
      volumes were quantified using: 1) manual delineation, 2) automated fuzzy c-means
      method, and 3) +2 to 6 SD thresholding approaches. Results were compared against
      peak values of serum Troponin I (TnI), creatine kinase (CK) and left ventricular
      (LV) functional parameters: LV ejection fraction (LVEF), indexed end-diastolic
      (EDVi), end-systolic volumes (ESVi) and the number of hypokinetic segments
      (NbHk). RESULTS: For CMI, quantitative evaluation of infarct size using manual,
      +2SD, +3 SD and fuzzy c-means provided equivalent results in terms of correlation
      coefficients for comparisons of MI volumes against LV function parameters (LVEF:
      r>0.79, p<0.0001; ESVi: r>0.82, p<0.0001, EDVi: r>0.67, p<0.0001, NbHk: r>0.54,
      p<0.0009). For AMI, +2SD and fuzzy c-means approaches provided higher
      correlations for comparisons of AMI volumes against biochemical markers (CK:
      r>0.79, p<0.0001,TnI: r>0.77, p<0.0001) and chronic LV function parameters (LVEF:
      r>0.82, p<0.0001, NbHk: r>0.59, p<0.0002). CONCLUSIONS: The fuzzy c-means and 2SD
      methods provided highest correlations with biochemical MI quantification as well
      as LV function parameters. The fuzzy c-means approach which does not require an
      arbitrary identification of the remote myocardium is fast and reproducible. It
      may be clinically useful in the evaluation of patients with MI.

PMID- 22459371
TI  - Antiplatelet theRapy after Genous EPC-capturing coroNary stenT implantatiOn: the
      ARGENTO study: a prospective, multicenter registry.
AB  - BACKGROUND: To investigate the safety and efficacy of Genous Bio-engineered R
      stent (GRS) with <= 15-day or >15-day dual antiplatelet therapy (DAT), in
      patients undergoing percutaneous coronary intervention (PCI), with known or
      expected low compliance to long-term DAT (Antiplatelet theRapy after Genous EPC
      capturing coroNary stenT implantatiOn--ARGENTO study). METHODS: Consecutive
      patients without <= 12-month revascularization history, known statins allergy,
      known hypersensitivity reaction or previous or concomitant monoclonal and/or
      recombinant antibodies therapy, treated with single- or multivessel PCI plus GRS,
      were prospectively enrolled, at four PCI centers. Major adverse cardiac events
      (MACEs), the composite of cardiac death, any myocardial infarction (MI) and
      target vessel revascularization (TVR), and stent thrombosis (ST) cumulative
      incidences were evaluated. RESULTS: Between March 2008 and March 2010, 384
      patients (70.3% male, 423 lesions) were enrolled. At follow-up (22.8 +/- 13.6
      months), 8.6% MACEs, 3.4% cardiac death, 3.4% any MI, 4.7% TVR and 2.3% overall
      ST (definite/probable ST 1.3%) rates were reported, without differences between
      <= 15-day and >15-day DAT groups. At Cox multivariable-adjusted regression
      analysis (Hosmer-Lemeshow statistic, p=0.50) female sex, diabetes, previous PCI
      history, <45% left ventricular ejection fraction at admission and lesion length
      were identified as independent MACE predictors. DAT time duration (hazard ratio
      1.98; 95% confidence interval 0.57-6.80, p=0.27) was not independent risk factor
      for MACEs. CONCLUSIONS: In consecutive, prospectively enrolled patients with PCI
      indication and known or supposed low compliance to long-term DAT, GRS
      implantation might be a safe and effective option regardless of DAT duration
      after stenting (<= 15 days or >15 days).

PMID- 22459372
TI  - An evidence-based hypothesis for beneficial effects of telmisartan on Marfan
      syndrome.

PMID- 22459373
TI  - Soluble epoxide hydrolase inhibitor: a potential target for regulating adipocyte
      dysfunction.

PMID- 22459374
TI  - Role of sympathetic nervous system in myocardial ischemia injury: beneficial or
      deleterious?

PMID- 22459375
TI  - Screening children with suspected myocarditis for global and regional myocardial
      dysfunction using two-dimensional speckle tracking echocardiography: is it of
      use?

PMID- 22459377
TI  - Carotid artery stenting: "good news" or "bad news" for post-procedural cognitive
      function?

PMID- 22459376
TI  - Flow mediated dilation and carotid intima media thickness: clinical markers or
      just research tools?

PMID- 22459378
TI  - Efficacy of bosentan therapy for segmental pulmonary artery hypertension due to
      major aortopulmonary collateral arteries in children.

PMID- 22459379
TI  - Reduced microvascular density in non-ischemic myocardium of patients with recent
      non-ST-segment-elevation myocardial infarction.
AB  - BACKGROUND: Myocardial microvascular dysfunction has been implicated in the
      pathogenesis of myocardial infarction (MI). We tested the hypothesis that
      patients with MI have lower microvasculature density in myocardium remote from
      the site of infarction than patients with similar extent of coronary artery
      disease (CAD) without MI and examined the relationship between myocardial
      capillary length density and plasma levels of angiogenesis-related biomarkers.
      METHODS: We analyzed biopsies from non-ischemic left ventricular (LV) myocardium
      and measured plasma levels of angiogenesis-related biomarkers in patients
      undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI)
      and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with
      biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV
      without CAD. RESULTS: Myocardial microvascular density of NSTEMI patients was
      approximately half the density of no-MI patients, and similar to AS patients.
      Whereas the reduced microvascular density of AS patients was accounted for by
      their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who
      had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV,
      and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine
      and low molecular weight fluorophores, higher vascular endothelial growth factor
      (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth
      factor levels than no-MI patients. CONCLUSIONS: Recent MI was associated with
      reduced microvasculature density in myocardium remote from the site of infarction
      and alteration in plasma levels of angiogenesis-related biomarkers.

PMID- 22459380
TI  - Inflammatory environment and immune responses to oxidized LDL are linked to
      systolic and diastolic blood pressure levels in hypertensive subjects.

PMID- 22459381
TI  - Bivalvular transcatheter treatment of high-surgical-risk patients with coexisting
      severe aortic stenosis and significant mitral regurgitation.
AB  - BACKGROUND: In inoperable or high-surgical-risk patients, transcatheter aortic
      valve replacement (TAVR) and repair of the mitral valve using the MitraClip have
      emerged as novel treatment strategies. We sought to assess the feasibility and
      effectiveness of bivalvular transcatheter therapy in patients with coexisting
      aortic stenosis and mitral regurgitation. METHODS: Out of 285 patients treated
      with TAVR and 226 patients who underwent MitraClip therapy at our institution, 11
      patients (78 +/- 6years, 9 men [82%]) received both therapies. TAVR preceded
      MitraClip therapy in 10 patients, with 3 patients undergoing both interventions
      in a single session. RESULTS: TAVR via transapical (n = 6) or transfemoral (n =
      5) access utilized the Sapien/Sapien XT and CoreValve prostheses in 7 and 4
      patients, respectively. All TAVR procedures were successful, with significant
      increases in effective aortic orifice area and decreases in mean transvalvular
      pressure gradient. MitraClip therapy succeeded in reducing MR severity to <2+ in
      10 patients. Periprocedurally, 1 patient sustained a stroke. At a median of 208
      days, 2 patients were in NYHA functional class II, with only 1 patient improved
      from before TAVR, and 6 patients were in class III (improvement in 1). Four
      patients had died at a median of 60 days after MitraClip therapy. CONCLUSION:
      Bivalvular transcatheter treatment of patients with coexisting aortic stenosis
      and MR is technically feasible, even in a single session. Given the low
      prevalence of midterm functional improvement, factors predictive of clinical
      benefit from catheter-based double-valve intervention remain to be determined.

PMID- 22459383
TI  - Optical coherence tomography: the face of coronary artery spasm.

PMID- 22459382
TI  - Residual atherothrombotic material after stenting in acute myocardial infarction-
      an optical coherence tomographic evaluation.
AB  - BACKGROUND: Thrombus aspiration (TA) in patients with ST segment elevation
      myocardial infarction (STEMI) results in a better myocardial perfusion. Optical
      coherence tomography (OCT) after stenting in STEMI, however, often reveals
      residual atherothrombotic material. We assessed the feasibility of quantification
      of residual atherothrombotic burden and its relation to indices of myocardial
      perfusion. The effect of TA on residual in-stent atherothrombotic burden (ATB) is
      explored. METHODS AND RESULTS: Forty patients with STEMI within 12h of symptom
      onset, underwent OCT after stent implantation. No complication related to the
      invasive imaging was detected and all cases had good image quality. All 40 cases
      revealed ATB (median, range; 2.85, 0.08-8.84) despite an optimal angiographic
      result. Patients were divided into two groups according to the ATB: >=
      4=ATB(high) (n=15) and <4=ATB(low) (n=25). Patients with ATB(low) more often
      obtained a myocardial blush grade (MBG) of 2/3: 24 (96%) vs. 11 (73%), p=0.04 and
      a >= 50% ST segment resolution 24 (96%) vs. 8 (53%) p=0.02. Incomplete stent
      apposition is more often detected with ATB(low): 1.97 (0.62-4.73) vs. 0.33 (0.04
      0.92), p=0.002. TA was performed in 20 (50%) patients. ATB was numerically lower
      in patients with TA: 2.37 (1.70-5.10) vs. 3.40 (1.45-4.96), p=0.67. Logistic
      regression identified ATB as predictor of ST resolution failure (OR: 2.5 (95%
      confidence interval: 1.27-4.98), p value=0.008). CONCLUSIONS: OCT can be safely
      performed in patients presenting for primary PCI and allows quantification of
      residual atherothrombotic material, the amount of which is associated with worse
      myocardial perfusion.

PMID- 22459384
TI  - Serial phase-contrast MRI for prediction of pulmonary hemodynamic changes in
      patients with pulmonary arterial hypertension.

PMID- 22459385
TI  - Serum C-reactive protein and carotid intima-media thickness.

PMID- 22459386
TI  - High mortality in diabetics with acute heart failure: concern about glyburide.

PMID- 22459387
TI  - Relationship between left ventricular dyssynchrony and systolic dysfunction is
      independent of impaired left ventricular myocardial perfusion in heart failure:
      assessment with 99mTc-sestamibi gated myocardial scintigraphy.
AB  - BACKGROUNDS: Left ventricular (LV) dyssynchrony reduces LV systolic function in
      patients with heart failure (HF). However, it remains unknown whether this
      relationship is independent of impaired LV myocardial perfusion. METHODS AND
      RESULTS: A total of 105 patients with chronic HF (age 71 +/- 13 years; 71 men)
      were enrolled in the present study. (99m)Tc-sestamibi (MIBI) gated myocardial
      scintigraphy was performed at rest to assess LV myocardial perfusion as evaluated
      by the total defect score of perfusion Single Photon Emission Computed Tomography
      images (TDS-MIBI), LV systolic function as evaluated by LV ejection fraction
      (LVEF), and LV systolic dyssynchrony as evaluated by the maximal difference of
      time to end systole (MD-TES), which is the time lag between the earliest and the
      latest end systole among 17 LV segments analyzed with a novel program,
      "cardioGRAF". The mean +/- SD (minimum and maximum range) of the MD-TES was 147.8
      +/- 117.5 (14.0-458.3)ms. The MD-TES was significantly higher in patients with
      LVEF<45% (199.4 +/- 117.6 ms) than in those with LVEF >= 45% (60.5 +/- 41.2 ms,
      p<0.001). In a multiple logistic regression analysis, the MD-TES showed an
      increased odds ratio for LVEF<45% (2.46 [95% CI; 1.51-4.01] per increment in
      decile of MD-TES rank, p<0.001), after adjusting for the TDS-MIBI, history of
      myocardial infarction, and other potential confounders. CONCLUSIONS: LV
      dyssynchrony is a significant determinant of LV systolic dysfunction in patients
      with HF, and this relationship is independent of impaired LV myocardial perfusion
      and history of myocardial infarction.

PMID- 22459388
TI  - Effects of vitamin D supplementation on markers of vascular function after
      myocardial infarction--a randomised controlled trial.
AB  - BACKGROUND: Low vitamin D levels are common, and are associated with a higher
      incidence of future vascular events. We tested whether vitamin D supplementation
      could improve endothelial function and other markers of vascular function in
      patients with a history of myocardial infarction. METHODS: Parallel group,
      placebo-controlled, double-blind randomised trial. Patients with a history of
      myocardial infarction were randomised to receive 100,000 units of oral vitamin D3
      or placebo at baseline, 2 months and 4 months. Outcomes were measured at
      baseline, 2 and 6 months. Reactive hyperaemia index on fingertip plethysmography
      was the primary outcome. Secondary outcome measures included blood pressure,
      cholesterol, C-reactive protein, von Willebrand factor, tumour necrosis factor
      alpha, E-selectin, B-type natriuretic peptide, thrombomodulin and 25
      hydroxyvitamin D levels. RESULTS: 75 patients were randomised, mean age 66 years.
      74/75 (99%) completed 6 month follow-up. 25 hydroxyvitamin D levels increased in
      the intervention group relative to placebo (+13 vs +1 nmol/L, p=0.04). There was
      no between-group difference in change in reactive hyperaemia index between
      baseline and 6 months (-0.18 vs -0.07, p=0.40). Of the secondary outcomes, only C
      reactive protein showed a significant decline in the intervention arm relative to
      placebo at 6 months (-1.3 vs 2.0mg/L, p=0.03). Systolic blood pressure (+1.4 vs
      +2.3 mmHg, p=0.79), diastolic blood pressure (+2.0 vs +0.8 mmHg, p=0.54) and
      total cholesterol (+0.26 vs +0.24 mmol/L, p=0.88) showed no between-group
      difference at 6 months. CONCLUSIONS: Supplementation with vitamin D did not
      improve markers of vascular function in patients with a history of myocardial
      infarction.

PMID- 22459390
TI  - Urinary albumin excretion regression in hypertensive individuals.

PMID- 22459389
TI  - CRP and suPAR are differently related to anthropometry and subclinical organ
      damage.
AB  - BACKGROUND: Low-grade inflammation is a marker for cardiovascular disease (CVD).
      The inflammatory biomarkers C-reactive protein (CRP) and soluble urokinase
      plasminogen activator receptor (suPAR) independently predict CVD. We tested the
      hypothesis that these biomarkers reflect different aspects of the inflammation
      associated with CVD. METHODS: We studied 2273 subjects without CVD. Log
      transformed CRP and suPAR were included in general linear and logistic regression
      models to compare associations with measures of anthropometry and subclinical
      organ damage (SOD). Owing to interactions on body mass index (BMI) (P<0.0001),
      the population was stratified by gender and smoking concerning anthropometry.
      RESULTS: In both genders, independent of smoking, log-CRP was positively
      associated with BMI (beta: 0.28 to 0.40, P<0.001) and waist circumference (WC)
      (beta: 0.27 to 0.42, P<0.001). In contrast, in smoking women and men, log-suPAR
      was negatively associated with BMI and WC (beta: -0.09 to -0.19, P<0.05). In non
      smoking women, log-suPAR was positively associated with BMI and WC (beta: 0.14
      and 0.16, P<0.001), whereas no associations were found in non-smoking men. No
      interactions were found on SOD. Adjusted for age, sex, smoking, and physical
      activity, log-suPAR was associated with an increased urine albumin/creatinine
      ratio (standardized odds ratio (95% confidence interval (CI)) for highest vs.
      lower quartiles: 1.36 (1.21-1.52), whereas log-CRP was not (1.10 (0.99-1.22))),
      and extent of atherosclerosis (standardized proportional odds ratio (95% CI) for
      carotid plaques 0, 1 <= to <= 3, >3: 1.31 (1.16-1.47), whereas log-CRP was not
      (1.00 (0.89-1.11))). CONCLUSIONS: CRP is positively associated with
      anthropometric measures, whereas suPAR is linked to endothelial dysfunction and
      atherosclerosis.

PMID- 22459391
TI  - Impact of coronary artery disease in elderly patients undergoing transcatheter
      aortic valve implantation: insight from the Italian CoreValve Registry.
AB  - BACKGROUND: Coronary artery disease (CAD) commonly coexists with degenerative
      aortic stenosis. The impact of CAD in patients undergoing transcatheter aortic
      valve implantation (TAVI) raises concerns due to the lack of comprehensive and
      consistent data on this topic. We sought to evaluate the impact of CAD on
      clinical outcomes in patients undergoing TAVI. METHODS: Consecutive
      patients(N=663) who underwent TAVI with the 18-French CoreValve ReValving System
      (CRS) (Medtronic Inc, MN USA) from June 2007 through December 2009 at 14
      institutions across Italy were included in this prospective web-based registry.
      Four patients were excluded from the analysis due to failure to successfully
      release the prosthesis inside the native aortic valve. Previous percutaneous or
      surgical myocardial revascularizations were used to identify the existence of
      concomitant CAD (N=251; 38%). The primary endpoint was the incidence of Major
      Adverse Cerebrovascular and Cardiac Events (MACCE) and all-cause death in CAD and
      no-CAD groups. RESULTS: Patients with CAD were no more likely to develop MACCE
      within 12-months of the procedure than those who did not (CAD group vs no-CAD
      group, 15.7% vs 18.3%; adjusted hazard ratio [HR] 0.76; 95% confidence interval
      [CI] 0.42 to 1.36; p=0.353). The 12-month mortality was 14.5% and 15.9% in CAD
      group and no-CAD group, respectively (adjusted HR 0.74; 95% CI 0.40 to 1.36;
      p=0.331). CONCLUSIONS: Coexisting CAD does not impact procedural outcomes and mid
      term incidence of MACCE and survival in elderly patients undergoing TAVI with CRS
      prosthesis.

PMID- 22459392
TI  - Prognostic value of plasma renin activity in heart failure patients with chronic
      kidney disease.
AB  - BACKGROUND: Impairment of kidney function is frequently observed in chronic heart
      failure (CHF). It correlates with clinical and neurohormonal status, and affects
      prognosis. We aimed to identify the prognostic impact of plasma renin activity
      (PRA) in patients affected by CHF with chronic kidney disease (CKD). METHODS: We
      enrolled 996 consecutive CHF patients (age 65 +/- 13 years, mean +/- SD, left
      ventricular ejection fraction, LVEF, 33 +/- 10%), who underwent a complete
      clinical and neurohormonal characterization and were then followed-up (median 36
      months) for the end point of cardiac death. RESULTS: A stage >= 3 CKD (estimated
      glomerular filtration rate <60 mL/min/1.73 m(2)) was found in 437 patients.
      Impaired renal function was associated with worse symptoms, lower LVEF, higher
      plasma norepinephrine, NT-proBNP and PRA (all p<0.001). As compared to patients
      with preserved renal function, those with CKD had higher cardiac mortality [106
      (24%) vs 53 (9.5%), p<0.001]. In CKD patients, at Cox multivariate analysis, only
      ejection fraction (HR 0.91, 95% CI 0.84-0.97, p=0.008), NT-proBNP (2.53, 1.45
      4.41, p=0.001) and PRA (1.73, 1.16-2.58, p=0.007) were independent predictors of
      cardiac death. ROC analysis identified a cut-off value for PRA of 3.29 ng/mL/h
      that predicted prognosis with the greatest accuracy. Finally, the elevation of
      both NT-proBNP and PRA identified a subset of patients with the highest risk of
      cardiac death. CONCLUSIONS: PRA has an independent prognostic value in CHF
      patients with CKD comorbidity. The combination of PRA and NT-proBNP identifies a
      group of high risk patients, who might benefit of a more intensive care, targeted
      to enhance renin-angiotensin system antagonism.

PMID- 22459393
TI  - Low self-estimated quality of life after myocardial infarction and future
      cardiovascular risk.

PMID- 22459394
TI  - Distinguishing incomplete right bundle branch block in patients with
      arrhythmogenic right ventricular cardiomyopathy from normal variants: a potential
      role of Fontaine leads and Holter monitoring?

PMID- 22459395
TI  - Endothelial dysfunction following drug-eluting stent implantation: a systematic
      review of the literature.
AB  - BACKGROUND: While several studies have reported endothelial dysfunction after
      drug-eluting stent (DES) implantation, their study methods differed and the
      results were varied. METHODS AND RESULTS: A literature search was performed using
      PubMed where 14 clinical studies (537 patients) including two randomized trials
      were identified. All studies assessed endothelial dysfunction 3-14 months after
      stent implantation. In the acetylcholine (ACh) loading studies, significant
      vasoconstrictions were observed in proximal and distal segments after
      implantation of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) and a
      milder diameter change was observed after zotarolimus-eluting stent (ZES)
      implantation. Coronary diameter changes were greater in distal segments.
      Significant diameter change was not detected after bare metal stent (BMS)
      implantation. In the exercise examinations, vasoconstriction was observed in
      distal and proximal segments following SES and PES implantation, whereas
      vasodilation was observed in BMS. In the pacing examinations, vasoconstriction
      was observed in both SES and PES implantations in distal and proximal segments,
      whereas vasodilation was observed in not only BMS but ZES and biolimus-eluting
      stents (BES) as well. CONCLUSION: In the chronic phase following stent
      implantation, marked abnormal vasoconstriction distally in the stent was observed
      in SES and PES implantation but not in ZES or BES, compared with BMS. To clarify
      the clinical implications and possible mechanisms of these findings, longer-term
      evaluation with larger patients is needed.

PMID- 22459396
TI  - Early and mid-term cardiovascular outcomes following TAVI: impact of pre
      procedural transvalvular gradient.
AB  - OBJECTIVE: To assess the relation of aortic transvalvular gradient with outcomes
      following transcatheter aortic valve implantation (TAVI). BACKGROUND: Relatively
      little is known about the predictors of adverse outcomes in patients with severe
      aortic stenosis following TAVI. METHODS: We studied 126 consecutive patients
      (mean age 83.2 +/- 6.3 years; 59% women) who underwent TAVI (23% transapical; 77%
      transfemoral) at our institution. All patients were followed for the incidence of
      major adverse cardiovascular events (MACE), including myocardial infarction,
      heart failure, stroke, and cardiovascular death. RESULTS: The acute procedural
      success rate was 98%; at 1 year, the cumulative incidence of MACE and
      cardiovascular death was 29% and 10%, respectively. In multivariable analyses
      adjusting for clinical and echocardiographic risk factors, presence of a baseline
      mean transvalvular gradient (MTG) <40 mmHg was a significant predictor of 30-day
      MACE in the total sample (OR 4.4, 95% CI 1.7-11.4; P=0.003) as well as in
      patients with an ejection fraction >= 50% (OR 10.3, 95% CI 3.0-33.4; P<0.001). In
      multivariable analyses, low MTG was also associated with 2-fold and 4-fold
      increased hazards for MACE (HR 4.2, 95% CI 2.0-8.9; P<0.001) and cardiovascular
      death (HR 4.2 95% CI 1.2-14.9; P=0.03), respectively, within 1 year following
      TAVI. CONCLUSION: Presence of a low MTG (<40 mmHg) prior to TAVI was associated
      with a greater risk of major adverse events, including cardiovascular death, up
      to 1 year following the procedure. Pre-procedural MTG could be used to identify
      patients at a high risk for adverse outcomes following TAVI.

PMID- 22459398
TI  - Anabolic androgenic steroid use is associated with ventricular dysfunction on
      cardiac MRI in strength trained athletes.
AB  - BACKGROUND: Uncertainty remains about possible cardiac adaptation to resistance
      training. Androgenic anabolic steroids (AAS) use plays a potential role and may
      have adverse cardiovascular effects. OBJECTIVE: To elucidate the effect of
      resistance training and of AAS-use on cardiac dimensions and function.
      PARTICIPANTS: Cardiac magnetic resonance (CMR) were performed in 156 male
      subjects aged 18-40 years: 52 non-athletes (maximum of 3 exercise hours/week), 52
      strength-endurance (high dynamic-high static, HD-HS) athletes and 52 strength
      (low dynamic-high static, LD-HS) trained athletes (athletes >= 6 exercise
      hours/week). 28 LD-HS athletes denied and 24 admitted to AAS use for an average
      duration of 5 years (range 3 months-20 years). RESULTS: No significant
      differences were found between non-athletes and non-AAS-using LD-HS athletes. AAS
      using LD-HS athletes had significantly larger LV and RV volumes and LV wall mass
      than non-AAS-using LD-HS athletes, but lower than HD-HS athletes. In comparison
      to all other groups AAS-using LD-HS athletes showed lower ejection fractions of
      both ventricles (LV/RV EF 51/48% versus 55-57/51-52%) and lower E/A ratios (LV/RV
      1.5/1.2 versus 1.9-2.0/1.4-1.5) as an indirect measure of diastolic function.
      Linear regression models demonstrated a significant effect of AAS-use on LV EDV,
      LV EDM, systolic function and mitral valve E/A ratio (all ANOVA-tests p<0.05).
      CONCLUSIONS: Strength athletes who use AAS show significantly different cardiac
      dimensions and biventricular systolic dysfunction and impaired ventricular inflow
      as compared to non-athletes and non-AAS-using strength athletes. Increased
      ventricular volume and mass did not exceed that of strength-endurance athletes.
      These findings may help raise awareness of the consequences of AAS use.

PMID- 22459399
TI  - Prevalence, risk, and benefits of radiofrequency catheter ablation at the aortic
      cusp for the treatment of mid- to anteroseptal supra-ventricular
      tachyarrhythmias.
AB  - BACKGROUND: Some outflow tract ventricular tachycardias (VTs) are known to be
      successfully ablated from the aortic cusp (AC). However, radiofrequency catheter
      ablation (RFCA) at the AC for the treatment of supraventricular tachyarrhythmia
      (SVT) has limited experience. METHODS: We performed RFCA at the AC in 19 patients
      (male 64.7%, 46.9 +/- 21.9 years old) with mid- to anteroseptal SVTs (12 atrial
      tachycardias [AT], 7 atrioventricular reciprocating tachycardia [AVRT]), and
      analyzed the prevalence, electrophysiologic findings, clinical outcome, and
      compilation risk. RESULTS: 1. Among 113 patients with AT, 13 patients had mid- to
      anteroseptal AT and 12 patients (8.8%, 53.4 +/- 19.8 years old, 58.3% female)
      underwent successful ablation from the non-coronary cusp (NCC; n=10), right CC
      (RCC; n=1) or left CC (LCC; n=1) without complication (3.1 +/- 2.3 times RF
      delivery, 6.15 +/- 3.08 s for termination). During 19.7 +/- 9.8 months of follow
      up, AT recurred in a patient with multiple foci. 2. Among 580 patients with AVRT,
      27 patients had a mid- to anteroseptal bypass tract (4.7%), and 7 of them (1.1%,
      2 pre-excitation syndrome, 5 concealed bypass tract) were successfully ablated at
      the NCC (n=2) or RCC (n=5) (7.0 +/- 7.1 times RF delivery, 9.1 +/- 4.4s for
      termination). Among 5 patients with AVRT successfully ablated at the RCC, one
      patient developed complete heart block 48 h after procedure, and 2 patients
      recurred AVRT or delta-wave in ECG during 13.9 +/- 11.7 month follow-up.
      CONCLUSION: Catheter ablation within the AC is an effective procedure to
      eliminate mid- to anteroseptal SVTs. However, RFCA on RCC requires a caution for
      heart block in our limited experience.

PMID- 22459397
TI  - QTc prolongation is associated with impaired right ventricular function and
      predicts mortality in pulmonary hypertension.
AB  - BACKGROUND: In rodent models of pulmonary hypertension (PH) and right ventricular
      hypertrophy (RVH), the QTc interval is prolonged, reflecting downregulation of
      repolarizing Kv channels in RV myocytes. The significance of QTc prolongation in
      human PH is unknown. We hypothesized that QTc prolongation occurs in human PH, is
      associated with RVH and decreased RV function, and predicts adverse prognosis.
      METHODS: Patients receiving a PAH-specific therapy (a prostanoid, endothelin
      receptor antagonist and/or a phosphodiesterase-5 inhibitor), who had a 12-lead
      electrocardiogram (ECG) (n=202) were compared to age- and sex-matched controls
      (n=100). The duration of QTc on ECG was correlated with invasive hemodynamics
      (n=156) and with the status of the RV, as measured by Brain Natriuretic Peptide
      (NT-proBNP, n=145) and magnetic resonance imaging (n=24). Survival of the entire
      PH cohort and a subgroup with WHO Groups 1 and 4 PAH was prospectively determined
      from the Social Security Death Index. RESULTS: QTc intervals were longer in PH
      vs. controls (454.8 +/- 29 ms vs. 429.8 +/- 18 ms, p<0.001) and did not differ
      based on PAH-specific therapy. NT-proBNP increased proportionately with QTc and
      was higher for those in the upper quintile (QTc >= 480 ms) vs. those with QTc<480
      ms (4004 +/- 6682 pg/mL vs. 1501 +/- 1822 pg/mL, p<0.001). The QTc interval also
      correlated directly with increasing RV end-diastolic volume (r=.67, p<0.001) and
      mass (r=.0.51, p<0.05), and inversely with RV ejection fraction (r=-.49, p<0.05).
      In the entire PH cohort and WHO Groups 1 and 4 subgroup, QTc >= 480 ms and
      cardiac index were independent predictors of mortality. CONCLUSIONS: QTc
      prolongation in PH patients reflects the status of the RV and is an independent
      predictor of mortality.

PMID- 22459400
TI  - Targeting cell death in the reperfused heart: pharmacological approaches for
      cardioprotection.
AB  - During acute myocardial infarction and in the reperfused heart, loss of
      cardiomyocytes is mostly caused by apoptosis and necrosis. As apoptosis was
      considered as the only form of regulated cell death for many years, initial
      studies investigating cardiomyocyte cell death mainly focused on direct
      inhibition of apoptosis. However, it has become clear that ischemic conditioning
      protocols--the application of alternating periods of non-lethal ischemia and
      reperfusion--can reduce necrotic cell death in the reperfused heart. Research on
      the signal-transduction pathways responsible for this phenomenon resulted in the
      discovery of many pharmacological targets to limit cell death after reperfusion,
      in which the activation of survival kinases and inhibition of mitochondrial
      permeability transition pore (MPTP) play an important role. Very recently, a
      regulated form of necrotic cell death (called 'necroptosis') was identified
      together with potential pharmacological inhibitors, which may also protect the
      myocardium from lethal reperfusion injury. This review highlights the role of
      apoptosis and necrosis in the reperfused hearts, including its execution and
      regulation and the emerging role of programmed necrosis (necroptosis).
      Furthermore, we will focus on the results of pharmacological interventions in
      experimental studies as well as relevant proof-of-concept clinical trials trying
      to limit apoptosis, necrosis and necroptosis in the reperfused heart. Although
      the list of cardioprotective compounds is promising, large multi-centre clinical
      trials, with enough statistical power, will be necessary to determine whether
      they can improve clinical outcome and can be applied in patients as adjuvant
      therapy next to reperfusion.

PMID- 22459401
TI  - Proteomic analysis of plasma samples from acute coronary syndrome patients - the
      pilot study.

PMID- 22459402
TI  - The implications of a fragmented QRS complex and newly reclassified revised
      cardiac risk index including fragmented QRS in patients undergoing non-cardiac
      vascular surgery.

PMID- 22459403
TI  - Revival of beta-blockers in arterial hypertension.

PMID- 22459404
TI  - Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation.
AB  - BACKGROUND: The deficiency in methyl donors, folate and vitamin B12, increases
      homocysteine and produces myocardium hypertrophy with impaired mitochondrial
      fatty acid oxidation and increased BNP, through hypomethylation of peroxisome
      proliferator-activated-receptor gamma co-activator-1alpha, in rat. This may help
      to understand better the elusive link previously reported between
      hyperhomocysteinemia and BNP, in human. We investigated therefore the influence
      of methyl donors on heart mitochondrial fatty acid oxidation and brain
      natriuretic peptide, in two contrasted populations. METHODS: Biomarkers of heart
      disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were
      assessed in 1020 subjects, including patients undergoing coronarography and
      ambulatory elderly subjects from OASI cohort. RESULTS: Folate deficit was more
      frequent in the coronarography population than in the elderly ambulatory
      volunteers and produced a higher concentration of homocysteine (19.3 +/- 6.8 vs.
      15.3 +/- 5.6, P<0.001). Subjects with homocysteine in the upper quartile (>= 18
      MUmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects)
      and of short chain-, medium chain-, and long chain-acylcarnitines, compared to
      those in the lower quartile (<= 12 MUmol/L), in both populations (P<0.001).
      Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium
      chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of
      decreased mitochondrial acyldehydrogenase activities (P<0.001). In multivariate
      analysis, homocysteine and long chain acylcarnitines were two interacting
      determinants of NT-pro-BNP, in addition to left ventricular ejection fraction,
      body mass index, creatinine and folate. CONCLUSIONS: This study showed that
      homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired
      mitochondrial fatty oxidation, in two contrasted populations.

PMID- 22459405
TI  - Selective derivatization of nucleotide diphosphate (NDP)-4-keto sugars for
      electrospray ionization-mass spectrometry (ESI-MS).
AB  - Nucleotide diphosphate (NDP) sugars are widely present in antibiotics and
      glycoconjugates, such as protein- and lipid-linked oligosaccharides, where they
      act as substrates for glycosyltransferase in eukaryotes and prokaryotes. Among
      NDP sugars, NDP-4-keto sugars are key intermediates in the synthesis of
      structurally diverse NDP sugars with different functional groups. However, the
      structural identification of the NDP-4-keto sugars via mass spectrometry
      (electrospray ionization-mass spectrometry (ESI-MS)) continues to be a challenge
      because of the carbonyl group in these sugars interferes with ionization process.
      In this study, we evaluated various hydroxylamine compounds for the
      derivatization of NDP-4-keto sugars, so that the detection of the sugars by ESI
      MS is more efficient. As a result, O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine
      was found to be the most effective tagging molecule for the detection of NDP-4
      keto sugars without being interfered by original MS. This method can be used for
      identifying NDP-4-keto sugars such as thymidine diphosphate (TDP)-, adenosine
      diphosphate (ADP)-, uridine diphosphate (UDP)-, and cytosine diphosphate (CDP)-4
      keto sugars as well as new NDP-4-keto-dehydratases.

PMID- 22459406
TI  - Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not
      cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies
      linked P123H beta-synuclein.
AB  - Epidemiological studies have shown that ibuprofen, a non-steroidal anti
      inflammatory drug, reduces the risk for neurodegenerative diseases such as
      Alzheimer's disease (AD) and Parkinson's disease (PD). In this context, it has
      been shown that chronic treatment with ibuprofen improves cognitive dysfunction
      and histopathologic outcome in mouse models of AD. However, the therapeutic
      effects of ibuprofen in animal models of PD and related synucleinopathies such as
      dementia with Lewy bodies (DLB) have not been investigated. Therefore, the main
      objective of this study was to determine if ibuprofen ameliorates neuropathology
      and cognitive dysfunction in a transgenic (tg) mouse expressing DLB-linked P123H
      beta-synuclein. P123H beta-synuclein tg mice and their non-tg littermates aged 3
      months were given ibuprofen in their diet (n=13). Controls did not receive
      ibuprofen (n=11). After 3 months, the mice were evaluated using a Morris water
      maze test, followed by neuropathological analyses. Compared to control P123H beta
      synuclein tg mice, P123H beta-synuclein tg mice that received ibuprofen had
      significantly reduced protein aggregation and astrogliosis. However, ibuprofen
      treatment produced little improvement of the learning disability of P123H beta
      synuclein tg mice in the Morris water maze test. These results suggest that
      amelioration of neuropathologies by ibuprofen does not necessarily lead to
      improved cognitive function in synucleinopathies such as DLB.

PMID- 22459407
TI  - Revisiting higher-order and large-scale chromatin organization.
AB  - The past several years has seen increasing appreciation for plasticity of higher
      level chromatin folding. Four distinct '30nm' chromatin fiber structures have
      been identified, while new in situ imaging approaches have questioned the
      universality of 30nm chromatin fibers as building blocks for chromosome folding
      in vivo. 3C-based approaches have provided a non-microscopic, genomic approach to
      investigating chromosome folding while uncovering a plethora of long-distance cis
      interactions difficult to accommodate in traditional hierarchical chromatin
      folding models. Recent microscopy based studies have suggested complex topologies
      co-existing within linear interphase chromosome structures. These results call
      for a reappraisal of traditional models of higher-level chromatin folding.

PMID- 22459408
TI  - Evaluation of in silico development of aquatic toxicity species sensitivity
      distributions.
AB  - Determining the sensitivity of a diversity of species to environmental
      contaminants continues to be a significant challenge in ecological risk
      assessment because toxicity data are generally limited to a few standard test
      species. This study assessed whether species sensitivity distributions (SSDs)
      could be generated with reasonable accuracy using only in silico modeling of
      toxicity to aquatic organisms. Ten chemicals were selected for evaluation that
      spanned several modes of actions and chemical classes. Median lethal
      concentrations (LC50s) were estimated using three internet-based quantitative
      structure activity relationship (QSAR) tools that employ different computational
      approaches: ECOSAR (Ecological Structure Activity Relationships), ASTER
      (Assessment Tools for the Evaluation of Risk), and TEST (Toxicity Estimation
      Software Tool). Each QSAR estimate was then used as input into the SSD module of
      the internet-based toxicity estimation program Web-ICE to generate an in silico
      estimated fifth percentile hazard concentration (HC5) for each of the ten
      chemicals. The accuracy of the estimated HC5s was determined by comparison to
      measured HC5s developed from an independent dataset of experimental acute
      toxicity values for a diversity of aquatic species. Estimated HC5s showed
      generally poor agreement with measured HC5s determined for all available aquatic
      species, but showed better agreement when species composition of the chemical
      specific SSDs were identical. These results indicated that LC50 variability and
      species composition were large sources of error in estimated HC5s. Additional
      research is needed to reduce uncertainty in HC5s using only in silico approaches
      and to develop computational approaches for predicting species sensitivity.

PMID- 22459409
TI  - Natural mixtures of persistent organic pollutants (POPs) suppress ovarian
      follicle development, liver vitellogenin immunostaining and hepatocyte
      proliferation in female zebrafish (Danio rerio).
AB  - Persistent organic pollutants such as polychlorinated biphenyls (PCBs),
      polybrominated diphenyl ethers (PBDEs) and dichlorodiphenyltrichloroethane (DDT)
      are present in high concentrations in livers of burbot (Lota lota) in Lake Mjosa,
      Norway. In order to assess effects of such pollutants on fish gonadal morphology,
      female zebrafish were exposed in two generations by food to mixtures of
      pollutants extracted from livers of burbot from Lake Mjosa (high and low dose)
      and Lake Losna, which represents background pollution, and compared to a control
      group. Ovarian follicle counts detected a significant decrease in late
      vitellogenic follicle stages in fish exposed to the Losna and the high
      concentrations of Mjosa mixtures in fish from the first generation. In addition,
      proliferation of granulosa cells, visualized by immunohistochemistry against
      proliferating cell nuclear antigen (PCNA), was decreased in all exposure groups
      in either early or late vitellogenic follicle stages compared to control. This
      was accompanied by increased apoptosis of granulosa cells. There was a decrease
      in proliferation of liver hepatocytes with exposure to both Mjosa mixtures. In
      addition, immunopositivity for vitellogenin in the liver was significantly lower
      in the Mjosa high group than in the control group. When analysing effects of
      parental exposure, fish with parents exposed to Mjosa high mixture had
      significantly higher numbers of perinucleolar follicles than fish with control
      parents. We conclude that long-term exposure of a real-life mixture of pollutants
      containing high- and background levels of chemicals supress ovarian follicle
      development, liver vitellogenin immunostaining intensity and hepatocyte
      proliferation in the zebrafish model.

PMID- 22459410
TI  - Growth, composition and metal removal potential of a Phormidium bigranulatum
      dominated mat at elevated levels of cadmium.
AB  - Prompted by the fact that interaction of metals with cyanobacterial mats has been
      little studied, the present study evaluates the response of a cyanobacterial mat,
      dominated by Phormidium bigranulatum, to elevated concentrations of Cd2+ in the
      medium. The mat failed to grow at 7 MUM of Cd2+ when the metal as also the mat
      inoculum were simultaneously added to the medium right in the beginning of the
      experiment due to marked sensitivity of P. bigranulatum, the main constituent of
      the mat, to high concentrations of Cd2+. However, the mat previously grown in
      Cd2+-free medium for a time period of 1-4 weeks grew successfully when exposed to
      media containing very high concentrations of Cd2+. Four-week-old mat could grow
      at 250 MUM of Cd2+, which has been found toxic to many cyanobacteria and algae by
      previous researchers. Greater tolerance of older mats to Cd2+ may be due to
      greater proportion of exopolysaccharides, which are well known to sequester metal
      ions extracellularly, in them. Whereas the relative proportion of P. bigranulatum
      declined at high concentrations of the test metal that of green algae increased
      due most likely to their tolerance to Cd2+. Air bubbles were seen entrapped in
      the mat due obviously to photosynthetic activity. Elevated concentrations of Cd2+
      reduced the number of air bubbles in the mat. Decline in number of air bubbles at
      high concentrations of metal ions was more prominent in the case of younger mat
      than in the older one. The present study also evaluated changes in species
      composition of mats of different age that were subsequently grown in Cd2+
      enriched culture medium. Younger mats showed change in species composition at
      very low concentrations of Cd2+, but older mats showed little changes even at
      very high concentrations of the test metal. Hence older mats more strongly
      resisted to changes in its species composition than the younger ones upon
      exposure to high concentrations of Cd2+. The growing mat successfully removed
      Cd2+ from the medium, which was greater at lower concentrations of Cd2+ in the
      external environment.

PMID- 22459411
TI  - Fathead minnow (Pimephales promelas) reproduction is impaired when exposed to a
      naphthenic acid extract.
AB  - Previous studies have demonstrated that oil sands process-affected water (OSPW)
      impairs the reproduction of fish and that naphthenic acids (NAs), a natural
      constituent of oil sands, are suspected of being responsible. This study
      evaluates the potential impact of NAs on the reproduction of adult fathead
      minnows (Pimephales promelas) under laboratory conditions. Fathead minnows
      exposed to a 10 mg/l naphthenic acid extract (NAE) for 21 days spawned fewer eggs
      and males had reduced expression of secondary sexual characteristics. Male
      fathead minnows exposed to a 5 mg/l NAE had lower plasma levels of 11
      ketotestosterone whereas those exposed to a 10 mg/l NAE had lower concentrations
      of both testosterone and 11-ketotestosterone. Since OSPW also contains high
      concentrations of salts, this study also investigated whether they modify the
      toxicity of NAEs. Spawning was significantly reduced in fathead minnows exposed
      to a 10 mg/l NAE alone and in combination with NaHCO3 (700 mg/l), typical of
      concentrations in OSPW(.) Interestingly, the addition of NaHCO3 reduced the
      inhibitory effects of the NAE on the numbers of reproductive tubercles and plasma
      testosterone levels. Further studies showed that NaHCO3 acted by reducing the
      uptake of the NAE to the fish. NaHCO3 but not NaCl or Na2SO4 reduced the acute
      toxic effects of the NAE on fathead minnow embryo and larvae mortality.
      Collectively, these studies show that the NAs in OSPW have the potential to
      negatively affect reproduction in fathead minnows and that HCO3- reduces the
      acute and chronic toxicity of NAs.

PMID- 22459412
TI  - The stone man (Myositis ossificans progressiva).

PMID- 22459414
TI  - Which treatments had been tapered or stopped in rheumatoid arthritis in long-term
      DAS28 remission following subcutaneous tumor-necrosis-factor blocker therapy? A
      retrospective experience on 43 patients.

PMID- 22459413
TI  - Can we improve the diagnosis of spondyloarthritis in patients with uncertain
      diagnosis? The EchoSpA prospective multicenter French cohort.
AB  - Power Doppler ultrasound (PDUS) has proved to be a highly sensitive tool for
      assessing enthesitis in spondyloarthritis (SpA). In patients with a suspected
      SpA, diagnosis could be improved by detecting enthesitis with PDUS. OBJECTIVE: To
      evaluate the performance of PDUS for the diagnosis of SpA alone or combined with
      other clinical, laboratory and imaging findings in patients consulting for a
      suspected SpA. METHODS: Prospective, multicenter French cohort study (Boulogne
      Billancourt, Brest, Caen, Grenoble, Marseille and Nancy). Outpatients consulting
      for symptoms suggestive of SpA (inflammatory back pain [IBP], arthritis or
      inflammatory arthralgia [IA], enthesitis or dactylitis [ED], HLA-B27 positive
      uveitis [B27+U], familiarity for SpA [Fam]) were recruited and followed up for at
      least 2 years. Sample size was set to 500 patients (for estimated prevalence of
      SpA of 30+/-5% after 2 years). At baseline, patients were submitted to
      standardized physical examination, pelvic X-ray, sacroiliac joints magnetic
      resonance imaging (MRI), HLA-B typing, and other tests judged useful for
      diagnosis. For each patient, a blinded PDUS examination of 14 enthesitic sites
      was performed at baseline and at years 1 and 2. Patients were planned to be
      followed during 5 years. The diagnosis of SpA ascertained by an experts'
      committee, blind to PDUS results, after at least 2 years of follow-up, with a
      revaluation of doubtful patients at 5 years will be used as gold standard for
      evaluating the diagnostic performance of PDUS and the best diagnostic procedure
      by combining PDUS, clinical symptoms and other tests. RESULTS: Between January
      2005 and September 2007, 489 patients were included (96% of the target
      population). Nineteen patients (0.2%) retired their informed consensus or were
      lost to follow-up immediately after their inclusion. At baseline, mean age of the
      470 remaining patients was 40 years, mean duration of symptoms was 6.1 years; 42%
      of them were HLA-B27+ and 63% were female. Primary inclusion criterion was IBP in
      53%, IA in 27%, ED in 9%, B27+U in 8% and Fam in 4%. Follow-up is still ongoing.
      CONCLUSION: We have set up a unique diagnostic cohort which includes the entire
      spectrum of SpA manifestations. By using PDUS we expected to improve the
      diagnostic procedure of SpA.

PMID- 22459415
TI  - Spondylarthritis and monoclonal gammopathy.

PMID- 22459416
TI  - Mortality in rheumatoid arthritis over the last fifty years: systematic review
      and meta-analysis.
AB  - OBJECTIVE: Mortality rates in patients with rheumatoid arthritis (RA) have been
      reported to be higher than for the general population. Fortunately, efficient
      therapies have reduced disease activity and may be able to diminish the excess
      mortality risk. This study was designed to investigate RA mortality over the last
      50 years by systematic review of the literature and meta-analysis. METHODS: Data
      to January 2010 in the Medline, Cochrane and Embase databases were searched with
      the keywords "rheumatoid arthritis", "epidemiologic methods" and "mortality".
      Inclusion criteria were (i) longitudinal study, (ii) early RA patients, (iii)
      number of deaths and mean patient follow-up. Incidence mortality rates (IMR) were
      calculated and standardized mortality rates (SMR) were extracted when available.
      A meta-analysis by periods of inclusion and a Poisson regression were used to
      model IMR. Available SMR were computed as a meta-analysis. RESULTS: A total of 11
      longitudinal studies starting from 1955 to 1995, representing 51,819 patients,
      met the inclusion criteria. Mean IMR was 2.7/100 person-years of follow-up (95%
      confidence interval [CI]: 2.2, 3.3) and ranged from 1.0 to 5.2/100 person-years.
      A decreasing IMR was found in the meta-analyses. Poisson regression analysis
      indicated a decrease in IMR of 2.3% per year (95%CI: 2.1; 2.6). SMR was available
      in 8 studies: the meta-SMR was 1.47 (95%CI: 1.19; 1.83) and no decrease was seen
      over time in the meta-regression. CONCLUSION: Mortality has decreased among RA
      patients over the past decades but remained higher than in the general population
      as assessed by the IMR and the SMR over time.

PMID- 22459418
TI  - REL polymorphisms and rheumatoid arthritis in the Tunisian population.

PMID- 22459417
TI  - Synovium CD20 expression is a potential new predictor of bone erosion progression
      in very-early arthritis treated by sequential DMARDs monotherapy -- a pilot study
      from the VErA cohort.
AB  - OBJECTIVE: Because available biomarkers (rheumatoid factors [RF], anti-cyclic
      citrullinated autoantibodies [anti-CCP2], erythrocyte sedimentation rate at 1st
      hour [ESR]/C-reactive peptide [CRP] and bone erosions) are insufficient to
      predict rheumatoid arthritis (RA) structural damage, to determine whether
      synovium expression of greater or equal to 1 markers could constitute new
      prognostic factor(s). METHOD: The study was conducted on 18 prospectively
      enrolled disease-modifying anti-rheumatic drug (DMARD)- and glucocorticoid-naive,
      VErA cohort patients with very-early arthritis (median duration: 4months).
      Recorded at baseline were: clinical and biological (serum ESR, CRP, RF-isotypes,
      anti-CCP2, osteoprotegerin, receptor activator of nuclear kappaB-ligand [RANK-L]
      and cartilage oligomeric matrix protein [COMP] levels) data; synovium expression
      (HLA-DR, CD163, CD3, CD20, VEGF, osteoprotegerin, RANK-L, Bcl2 and global
      inflammation index) for a metacarpophalangeal joint-synovium biopsy. Baseline and
      3-year hand-and-foot X-rays were graded with the van der Heijde-modified-Sharp
      score; the judgment criterion was its progression during follow-up. Pearson's
      product moment correlation statistics were used to test for association between
      paired samples. RESULTS: A baseline, a significant relationship was found between
      erosive damage and markers of B-cell activation, notably the synovium CD20
      expression (r=0.68; P=0.0001). Quantified by the modified-Sharp erosion score
      variation, the 3-year structural damage progression was significantly correlated
      with: serum levels of RF-IgG (r=0.75; P=0.0003), -IgM (r=0.69; P=0.001), anti
      CCP2 (r=0.53; P=0.02) and RANK-L (r=0.61; P=0.007); synovium CD20 expression
      (r=0.70; P=0.001). CONCLUSION: This analysis of the prognostic value of a large
      panel of synovium markers in a limited sample of prospectively followed, well
      documented patients suggested that both synovial CD20 and serum RANK-L levels
      might be new predictors of structural damage progression in very-early RA.

PMID- 22459419
TI  - Lack of association between PADI4 polymorphisms and rheumatoid arthritis in the
      Tunisian population.

PMID- 22459420
TI  - Conditioning of sewage sludge by Fenton's reagent combined with skeleton
      builders.
AB  - Physical conditioners, often known as skeleton builders, are commonly used to
      improve the dewaterability of sewage sludge. This study evaluated a novel joint
      usage of Fenton's reagent and skeleton builders, referred to as the F-S inorganic
      composite conditioner, focusing on their efficacies and the optimization of the
      major operational parameters. The results demonstrate that the F-S composite
      conditioner for conditioning sewage sludge is a viable alternative to
      conventional organic polymers, especially when ordinary Portland cement (OPC) and
      lime are used as the skeleton builders. Experimental investigations confirmed
      that Fenton reaction required sufficient time (80 min in this study) to degrade
      organics in the sludge. The optimal condition of this process was at pH=5,
      Fe(2+)=40 mg g(-1) (dry solids), H(2)O(2)=32 mg g(-1), OPC=300 mg g(-1) and
      lime=400 mg g(-1), in which the specific resistance to filtration reduction
      efficiency of 95% was achieved.

PMID- 22459421
TI  - Toxicity assessment of 45 pesticides to the epigeic earthworm Eisenia fetida.
AB  - This study was conducted to investigate comparative toxicity of 45 pesticides,
      including insecticides, acaricides, fungicides, and herbicides, toward the
      epigeic earthworm Eisenia fetida. Results from a 48-h filter paper contact test
      indicated that clothianidin, fenpyroximate, and pyridaben were supertoxic to E.
      fetida with LC(50) values ranging from 0.28 (0.24-0.35) to 0.72 (0.60-0.94) MUg
      cm(-2), followed by carbaryl, pyridaphenthion, azoxystrobin, cyproconazole, and
      picoxystrobin with LC(50) values ranging from 2.72 (2.22-0.3.19) to 8.48 (7.38
      10.21) MUg cm(-2), while the other pesticides ranged from being relatively
      nontoxic to very toxic to the worms. When tested in artificial soil for 14 d,
      clothianidin and picoxystrobin showed the highest intrinsic toxicity against E.
      fetida, and their LC(50) values were 6.06 (5.60-6.77) and 7.22 (5.29-8.68) mg kg(
      1), respectively, followed by fenpyroximate with an LC(50) of 75.52 (68.21-86.57)
      mgkg(-1). However, the herbicides fluoroglycofen, paraquat, and pyraflufen-ethyl
      exhibited the lowest toxicities with LC(50) values>1000 mg kg(-1). In contrast,
      the other pesticides exhibited relatively low toxicities with LC(50) values
      ranging from 133.5 (124.5-150.5) to 895.2 (754.2-1198.0) mg kg(-1). The data
      presented in this paper provided useful information for evaluating the potential
      risk of these chemicals to soil invertebrates.

PMID- 22459422
TI  - Change of PCBs and forms of heavy metals in sewage sludge during thermophilic
      anaerobic digestion.
AB  - Determination of seven congeners of PCBs was carried out for sewage sludge
      before, during and after thermophilic digestion. The overall content of heavy
      metals (Zn, Cu, Ni, Cd, Pb, Cr) in sludge before and after digestion was
      determined. Moreover the concentration of heavy metals in particular chemical
      fractions of the sludge was analyzed. After the thermophilic digestion total
      concentration of seven PCBs was reduced by 47%, which suggests that thermophilic
      digestion affects PCB reduction positively. On the 10th d of the process,
      concentration of lower chlorinated PCBs increased, whereas those of higher
      chlorinated PCBs decreased. The thermophilic digestion process showed no
      accumulation of the studied heavy metals in the mobile fractions (exchangeable
      and carbonate) of the stabilized sewage sludge, except for nickel. The highest
      increase in zinc, copper, cadmium, and chromium concentration was observed in the
      organic-sulfide fraction, whereas the highest increase in lead was found in the
      residual fraction of the sludge. In case of nickel both fractions of organic
      sulfide and exchangeable-carbonate fractions were enriched.

PMID- 22459423
TI  - A retrospective comparison of four plate constructs for first metatarsophalangeal
      joint fusion: static plate, static plate with lag screw, locked plate, and locked
      plate with lag screw.
AB  - The primary treatment for progressive first metatarsophalangeal (MTP) joint
      arthritis is arthrodesis. Multiple fixation types have been used to accomplish
      fusion including plating. There have been no published articles reporting the
      outcomes of these 4 plate and/or screw constructs. We present our experience with
      138 first MTP joint fusions using these constructs. A retrospective comparison
      and radiographic chart review of 132 patients (138 feet) was performed to compare
      different constructs in regards to successful union and time to fusion. All
      operations were performed by 4 fellowship-trained foot and ankle surgeons. The
      radiographs were independently read by 2 authors not involved in the index
      procedures. Radiographic fusion was determined by bridging cortices across the
      joint line. The mean time to union (in days) and rate of fusion were static
      plate: 59, 95%, static plate with lag screw: 56, 86%, locked plate: 66, 92%, and
      locked plate with lag screw: 53, 96%. There was not a statistically significant
      difference between the groups in regards to patient age, time to weight bearing,
      time to fusion, or rate of fusion. We report on the results of fusion comparing 4
      different plate and/or screw constructs for first MTP joint fusion. The data
      reveal no significant difference in time to fusion or rate of fusion between
      static and locked plates, with or without a lag screw.

PMID- 22459424
TI  - Hallux saltans due to flexor hallucis longus entrapment at a previously
      unreported site in an unskilled manual laborer: a case report.
AB  - Triggering of the big toe, or hallux saltans, is commonly due to stenosing
      tenosynovitis of the flexor hallucis longus at the fibro-osseous tunnel below the
      sustentaculum tali. It is a rare condition described mainly in female ballet
      dancers. This is hypothesized to be due to the en pointe position used in ballet,
      which puts enormous supraphysiologic loads on the flexor hallucis longus,
      predisposing it to injury. Trigger hallux is extremely uncommon in the general
      population. We are reporting a case of hallux saltans in an unskilled manual
      laborer, with the site of tendon entrapment just proximal to the medial malleolus
      in the distal leg, a hitherto unreported location of stenosis.

PMID- 22459425
TI  - Subungual melanoma of the great toe in a Hispanic male with Down syndrome: a case
      report and review of the literature.
AB  - Solid mass tumors are not as common as leukemia in individuals with Down
      syndrome. In this report, we describe the rare case of an adult Hispanic male
      with Down syndrome who developed advanced subungual melanoma in the hallux. We
      also describe the course of treatment, which involved hallux amputation along
      with metastatic work-up and sentinel lymph node biopsy with eventual resection.

PMID- 22459426
TI  - In vitro encystment of Himasthla elongata cercariae (Digenea, Echinostomatidae)
      in the haemolymph of blue mussels Mytilus edulis as a tool for assessing
      cercarial infectivity and molluscan susceptibility.
AB  - Infectivity of Himasthla elongata cercariae to mussels, their second intermediate
      hosts, and resistance by these hosts to infection were assessed on the basis of
      the cercariae's ability to encyst in mussel haemolymph in vitro. A series of
      experimental in vivo infections of mussels with batches of cercariae, each batch
      released from a different single infected mollusc and referred to as a clone (due
      to their shared genotype), demonstrated that the results of the in vitro tests
      corresponded to the actual indices of infectivity/susceptibility of the parasites
      and their hosts. Most cercarial clones had high infectivity, with a few clones
      having very high or, at the other extreme, very low infectivity. A similar
      pattern was revealed in mussel resistance to cercarial infection. Most of the
      molluscs tested were moderately susceptible to cercarial infection, but at each
      extreme a small fraction (less than 10%) displayed very high or very low
      susceptibility. It was shown that there were no totally compatible or totally
      incompatible 'cercaria clone/mussel' combinations. Results obtained are compared
      with the data on intra-population variability using the characters parasite
      infectivity/host compatibility for trematode/mollusc-first intermediate host
      associations. Results are made relevant to actual infection levels in mussel
      settlements at the White Sea.

PMID- 22459427
TI  - Measurement properties of patient-specific instruments measuring physical
      function.
AB  - OBJECTIVE: To identify patient-specific self-assessment instruments, which
      measure physical function in patients with musculoskeletal disorders and to
      evaluate the descriptive properties and the psychometric qualities of these
      instruments. STUDY DESIGN AND SETTING: After a systematic search, included
      instruments were evaluated psychometrically by the checklist "quality criteria
      for measurement properties of health status instruments." RESULTS: Twenty-three
      studies were included, referring to 12 instruments. Nine different versions of
      the Patient-Specific Functional Scale (PSFS) were identified. The practical
      elaboration of the different versions of the PSFS varied widely. None of the
      instruments were tested on all psychometric quality criteria of the checklist.
      The PSFS described by Cleland et al. was most extensively investigated and
      obtained exclusively positive scores. Overall, construct validity, reliability,
      and responsiveness were evaluated most frequently. CONCLUSION: The descriptive
      properties and psychometric quality of patient-specific instruments measuring
      physical function are only partly investigated. The PSFS was the most
      investigated instrument: nine different versions have been evaluated
      psychometrically. The version of Cleland et al. was most extensively
      investigated, obtained exclusively positive scores following the quality criteria
      by Terwee et al., and could be recommended for clinical use therefore. Future
      research will be necessary to confirm the psychometric quality of patient
      specific instruments measuring physical function in patients with musculoskeletal
      disorders.

PMID- 22459428
TI  - Reporting of methods was better in the Clinical Trials Registry-India than in
      Indian journal publications.
AB  - OBJECTIVE: We sought to evaluate if editorial policies and the reporting quality
      of randomized controlled trials (RCTs) had improved since our 2004-05 survey of
      151 RCTs in 65 Indian journals, and to compare reporting quality of protocols in
      the Clinical Trials Registry-India (CTRI). STUDY DESIGN AND SETTING: An
      observational study of endorsement of Consolidated Standards for the Reporting of
      Trials (CONSORT) and International Committee of Medical Journal Editors (ICMJE)
      requirements in the instructions to authors in Indian journals, and compliance
      with selected requirements in all RCTs published during 2007-08 vs. our previous
      survey and between all RCT protocols in the CTRI on August 31, 2010 and published
      RCTs from both surveys. RESULTS: Journal policies endorsing the CONSORT statement
      (22/67, 33%) and ICMJE requirements (35/67, 52%) remained suboptimal, and only 4
      of 13 CONSORT items were reported in more than 50% of the 145 RCTs assessed.
      Reporting of ethical issues had improved significantly, and that of methods
      addressing internal validity had not improved. Adequate methods were reported
      significantly more frequently in 768 protocols in the CTRI, than in the 296
      published trials. CONCLUSION: The CTRI template facilitates the reporting of
      valid methods in registered trial protocols. The suboptimal compliance with
      CONSORT and ICMJE requirements in RCTs published in Indian journals reduces
      credibility in the reliability of their results.

PMID- 22459430
TI  - Diagnostic interval and mortality in colorectal cancer: U-shaped association
      demonstrated for three different datasets.
AB  - OBJECTIVE: To test the theory of a U-shaped association between time from the
      first presentation of symptoms in primary care to the diagnosis (the diagnostic
      interval) and mortality after diagnosis of colorectal cancer (CRC). STUDY DESIGN
      AND SETTING: Three population-based studies in Denmark and the United Kingdom
      using data from general practitioner's questionnaires, interviewer-administered
      patient questionnaires, and primary care records, respectively. RESULTS: Despite
      variations in the potential selection and information bias when using different
      methods of identifying the date of first presentation, the association between
      the length of the diagnostic interval and 5-year mortality rate after the
      diagnosis of CRC was the same for all three types of data: displaying a U-shaped
      association with decreasing and subsequently increasing mortality with longer
      diagnostic intervals. CONCLUSION: Unknown confounding and in particular
      confounding by indication is likely to explain the counterintuitive findings of
      higher mortality among patients with very short diagnostic intervals, but cannot
      explain the increasing mortality with longer diagnostic intervals. The results
      support the theory that longer diagnostic intervals cause higher mortality in
      patients with CRC.

PMID- 22459429
TI  - Multiple imputation of missing repeated outcome measurements did not add to
      linear mixed-effects models.
AB  - OBJECTIVE: To assess the added value of multiple imputation (MI) of missing
      repeated outcomes measures in longitudinal data sets analyzed with linear mixed
      effects (LME) models. STUDY DESIGN AND SETTING: Data were used from a trial on
      the effects of Rosuvastatin on rate of change in carotid intima-media thickness
      (CIMT). The reference treatment effect was derived from a complete data set.
      Scenarios and proportions of missing values in CIMT measurements were applied and
      LME analyses were used before and after MI. The added value of MI, in terms of
      bias and precision, was assessed using the mean-squared error (MSE) of the
      treatment effects and coverage of the 95% confidence interval. RESULTS: The
      reference treatment effect was -0.0177 mm/y. The MSEs for LME analysis without
      and with MI were similar in scenarios with up to 40% missing values. Coverage was
      large in all scenarios and was similar for LME with and without MI. CONCLUSION:
      Our study empirically shows that MI of missing end point data before LME analyses
      does not increase precision in the estimated rate of change in the end point.
      Hence, MI had no added value in this setting and standard LME modeling remains
      the method of choice.

PMID- 22459431
TI  - Is Trypanosoma vivax genetically diverse?

PMID- 22459432
TI  - Developments in RNA interference and genetic transformation to define gene
      function in parasitic helminths.

PMID- 22459433
TI  - The development of RNA interference (RNAi) in gastrointestinal nematodes.
AB  - Despite the utility of RNAi for defining gene function in Caenorhabditis elegans
      and early successes reported in parasitic nematodes, RNAi has proven to be
      stubbornly inconsistent or ineffective in the animal parasitic nematodes examined
      to date. Here, we summarise some of our experiences with RNAi in parasitic
      nematodes affecting animals and discuss the available data in the context of our
      own unpublished work, taking account of mode of delivery, larval activation, site
      of gene transcription and the presence/absence of essential RNAi pathway genes as
      defined by comparisons to C. elegans. We discuss future directions briefly
      including the evaluation of nanoparticles as a means to enhance delivery of
      interfering RNA to the target worm tissue.

PMID- 22459434
TI  - FMRI connectivity analysis of acupuncture effects on the whole brain network in
      mild cognitive impairment patients.
AB  - The increased risk for the elderly with mild cognitive impairment (MCI) to
      progress to Alzheimer's disease makes it an appropriate condition for
      investigation. While the use of acupuncture as a complementary therapeutic method
      for treating MCI is popular in certain parts of the world, the underlying
      mechanism is still elusive. We sought to investigate the acupuncture effects on
      the functional connectivity throughout the entire brain in MCI patients compared
      to healthy controls (HC). The functional magnetic resonance imaging experiment
      was performed with two different paradigms, namely, deep acupuncture (DA) and
      superficial acupuncture (SA), at acupoint KI3. We first identified regions
      showing abnormal functional connectivity in the MCI group compared to HC during
      the resting state and subsequently tested whether these regions could be
      modulated by acupuncture. Then, we made the comparison of MCI vs. HC to test
      whether there were any specific modulatory patterns in the poststimulus resting
      brain between the two groups. Finally, we made the comparisons of DA vs. SA in
      each group to test the effect of acupuncture with different needling depths. We
      found the temporal regions (hippocampus, thalamus, fusiform gyrus) showing
      abnormal functional connectivity during the resting state. These regions are
      implicated in memory encoding and retrieving. Furthermore, we found significant
      changes in functional connectivity related with the abnormal regions in MCI
      patients following acupuncture. Compared to HC, the correlations related with the
      temporal regions were enhanced in the poststimulus resting brain in MCI patients.
      Compared to SA, significantly increased correlations related with the temporal
      regions were found for the DA condition. The enhanced correlations in the memory
      related brain regions following acupuncture may be related to the purported
      therapeutically beneficial effects of acupuncture for the treatment of MCI. The
      heterogeneous modulatory patterns between DA and SA may suggest that deep muscle
      insertion of acupuncture is necessary to achieve the appreciable clinical effect.

PMID- 22459435
TI  - Impact of diffusion-weighted MR imaging on the characterization of small
      hepatocellular carcinoma in the cirrhotic liver.
AB  - PURPOSE: The purpose of this study was to determine whether or not adding
      diffusion-weighted magnetic resonance imaging (DWI) to conventional magnetic
      resonance (MR) imaging sequences improves the characterization of small
      hepatocellular carcinoma (HCC) (<=2 cm) in the setting of cirrhotic liver
      compared to conventional sequences alone. MATERIALS AND METHODS: A total of 62
      cirrhotic liver patients with 82 nodules smaller than 2 cm in diameter were
      enrolled, and all lesions were pathologically confirmed. For the first reading
      session, which included precontrast T1- and T2-weighted images and T1 dynamic
      contrast-enhanced images, preindicated lesions by a study coordinator were
      characterized by two radiologists. They determined the confidence levels in
      consensus for the presence of small HCC into four grades. In another session,
      respiratory-triggered diffusion-weighted MR images (b factor=50, 400 and 800
      s/mm(2)) were added to the previously reviewed images, and the same two
      radiologists again determined the confidence levels. The diagnostic performance
      of the combined DWI-conventional sequences set and the conventional sequences
      alone set was evaluated using receiver operating characteristic curves.
      Sensitivity and specificity values for characterizing small HCCs were also
      calculated. RESULTS: The area under the receiver operating characteristic curve
      for the second interpretation session (0.86) was significantly higher (P=.038)
      than that of the first session (0.76). The sensitivity was significantly
      increased from 75.7% to 87.8% by adding DWI to the conventional sequences
      (P=.015). No significant differences were observed for specificity values.
      CONCLUSION: Adding DWI to conventional imaging modalities improves the diagnosis
      of small HCCs in the cirrhotic liver in terms of diagnostic performance and
      sensitivity by increasing reader confidence.

PMID- 22459436
TI  - Contrast-material-enhanced MR urography in evaluation of postoperative lower
      urinary tract fistulae and leakages.
AB  - Urinary fistulas and leakages of lower urinary tract are serious complications of
      various surgical procedures. Radiologists need to have enough information about
      these situations to perform precise diagnosis and treatment. Various techniques
      [such as intravenous pyelography, ultrasound, computed tomography (CT), CT
      urography, cystoscopy, cystography and magnetic resonance (MR) imaging] are used
      for the diagnosis of these conditions. Application of all these techniques
      reduces the comfort and cooperation of the patients and increases the cost. Here
      we present four postoperative patients with lower urinary tract fistula or
      leakage. To the best of our knowledge, there is no report regarding the use of
      contrast-material-enhanced MR urography (CE-MRU) in the demonstration of
      postoperative lower urinary tract fistulae and leakages. In conclusion, CE-MRU
      could show the existence and location of the urinary fistulae and leakages
      clearly without the need for another investigation technique, as described in our
      patients. Also, CE-MRU is a safe and relatively inexpensive technique that avoids
      exposure to radiation as well as nephrotoxic and more allergic contrast-material
      administration.

PMID- 22459437
TI  - Potential clinical factors affecting hepatobiliary enhancement at Gd-EOB-DTPA
      enhanced MR imaging.
AB  - OBJECTIVE: The objective was to clarify the clinical factors that might affect
      the degree of hepatic parenchymal enhancement at gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: A total of 84 patients with (n=63) and
      without chronic liver disease (n=21) underwent Gd-EOB-DTPA-enhanced MR imaging.
      Contrast-enhanced MR images of hepatobiliary phase (HP) were obtained at 20 min
      after Gd-EOB-DTPA administration. The relative enhancement (RE) of liver
      parenchyma at 20 min HP was calculated from region of interest measurements at
      each patient. Then, these results were correlated with various clinical
      parameters using Pearson correlation coefficient or Spearman rank correlation
      coefficient. Furthermore, the predictor of the degree of hepatic parenchymal
      enhancement was determined using multiple regression analysis. RESULTS: The
      presence or absence of chronic liver disease (P=.002), ascites (P=.005) and
      splenomegaly (P=.027), and the values of prothrombin activity (P=.008), total
      bilirubin (T-Bil) (P=.001), albumin (P=.001), aspartate aminotransferase (AST)
      (P=.002) and cholinesterase (P=.007) were significantly correlated with the RE of
      liver parenchyma at 20 min HP. Among these parameters, increases of T-Bil (P=.011
      to .028) and AST (P=.018 to .049) were predictors of decreased hepatic
      parenchymal enhancement. CONCLUSIONS: Hepatic parenchymal enhancement of Gd-EOB
      DTPA was affected by various clinical parameters. Impaired hepatobiliary
      enhancement may be predicted by routine biochemical tests, such as T-Bil and AST.

PMID- 22459438
TI  - Relayed magnetization transfer from nuclear Overhauser effect and chemical
      exchange observed by in vivo 31P MRS in rat brain.
AB  - The (31)P magnetization transfer effects among nuclear magnetic resonances (NMRs)
      of phosphocreatine (PCr), gamma-adenosine-5'-triphosphate (gamma-ATP) and
      inorganic phosphate (Pi) have been attributed to the chemical exchange reactions
      among PCr, ATP and Pi catalyzed by creatine kinase (CK) and ATPase enzymes and,
      therefore, are commonly applied in situ to measure chemical exchange fluxes
      involving two chemically coupled CK and ATPase reactions (i.e., PCr<->ATP<->Pi)
      by selectively saturating gamma-ATP resonance. Besides the expected reductions in
      the Pi and PCr NMR signals upon saturating gamma-ATP resonance, one particularly
      interesting phenomenon showing decreases in alpha-ATP and beta-ATP signals was
      also observed. The underlying mechanism was investigated and identified via
      saturating NMR of beta-ATP in the present study. The unique relayed magnetization
      transfer effects through spin diffusion were observed in the rat brain using in
      vivo (31)P magnetic resonance spectroscopy.

PMID- 22459439
TI  - Effect of nonrigid registration algorithms on deformation-based morphometry: a
      comparative study with control and Williams syndrome subjects.
AB  - Deformation-based morphometry (DBM) is a widely used method for characterizing
      anatomical differences across groups. DBM is based on the analysis of the
      deformation fields generated by nonrigid registration algorithms, which warp the
      individual volumes to a DBM atlas. Although several studies have compared
      nonrigid registration algorithms for segmentation tasks, few studies have
      compared the effect of the registration algorithms on group differences that may
      be uncovered through DBM. In this study, we compared group atlas creation and DBM
      results obtained with five well-established nonrigid registration algorithms
      using 13 subjects with Williams syndrome and 13 normal control subjects. The five
      nonrigid registration algorithms include the following: (1) the adaptive bases
      algorithm, (2) the image registration toolkit, (3) The FSL nonlinear image
      registration tool, (4) the automatic registration tool, and (5) the normalization
      algorithm available in Statistical Parametric Mapping (SPM8). Results indicate
      that the choice of algorithm has little effect on the creation of group atlases.
      However, regions of differences between groups detected with DBM vary from
      algorithm to algorithm both qualitatively and quantitatively. Some regions are
      detected by several algorithms, but their extent varies. Others are detected only
      by a subset of the algorithms. Based on these results, we recommend using more
      than one algorithm when performing DBM studies.

PMID- 22459441
TI  - Quantitative comparison between a multiecho sequence and a single-echo sequence
      for susceptibility-weighted phase imaging.
AB  - The aim of this study was to investigate the benefits arising from the use of a
      multiecho sequence for susceptibility-weighted phase imaging using a quantitative
      comparison with a standard single-echo acquisition. Four healthy adult volunteers
      were imaged on a clinical 3-T system using a protocol comprising two different
      three-dimensional susceptibility-weighted gradient-echo sequences: a standard
      single-echo sequence and a multiecho sequence. Both sequences were repeated twice
      in order to evaluate the local noise contribution by a subtraction of the two
      acquisitions. For the multiecho sequence, the phase information from each echo
      was independently unwrapped, and the background field contribution was removed
      using either homodyne filtering or the projection onto dipole fields method. The
      phase information from all echoes was then combined using a weighted linear
      regression. R2 maps were also calculated from the multiecho acquisitions. The
      noise standard deviation in the reconstructed phase images was evaluated for six
      manually segmented regions of interest (frontal white matter, posterior white
      matter, globus pallidus, putamen, caudate nucleus and lateral ventricle). The use
      of the multiecho sequence for susceptibility-weighted phase imaging led to a
      reduction of the noise standard deviation for all subjects and all regions of
      interest investigated in comparison to the reference single-echo acquisition. On
      average, the noise reduction ranged from 18.4% for the globus pallidus to 47.9%
      for the lateral ventricle. In addition, the amount of noise reduction was found
      to be strongly inversely correlated to the estimated R2 value (R=-0.92). In
      conclusion, the use of a multiecho sequence is an effective way to decrease the
      noise contribution in susceptibility-weighted phase images, while preserving both
      contrast and acquisition time. The proposed approach additionally permits the
      calculation of R2 maps.

PMID- 22459440
TI  - Effect of ovariectomy on contrast agent diffusion into lumbar intervertebral
      disc: a dynamic contrast-enhanced MRI study in female rats.
AB  - PURPOSE: The purpose was to study the effect of estrogen deficiency on contrast
      agent diffusion into intervertebral disc in a rat model. MATERIALS AND METHODS:
      Seven-month-old female Sprague-Dawley rats were used. Fourteen rats had
      ovariectomy, and nine rats had sham surgery. Magnetic resonance imaging (MRI) of
      sagittal midsection of lumbar spine was performed with a 1.5-T magnet. Dynamic
      MRI was performed after a bolus injection of Gd-DOTA (0.3 mmol/kg) through tail
      vein. Eight hundred images were acquired at 0.6 s per acquisition. Regions of
      interests were drawn over three discs per rat. Maximum enhancement (E(max)) and
      enhancement slope (E(slope)) were evaluated. MRI was carried out at baseline and
      8 weeks postsurgery. RESULT: All disc enhancements demonstrated an initial fast
      wash-in phase followed by a second slower wash-in phase. For initial wash-in
      phase, E(1)(max) and E(1)(slope) of all rats remained unchanged at the two time
      points. For second wash-in phase, E(2)(max) and E(2)(slope) of control rats
      remained unchanged, while with ovariectomized rats, E(2)(max) showed reduction at
      8 weeks (4.5%+/-5.6%) compared to baseline (10.3%+/-6.3%, P=.037), and
      E(2)(slope) was lower at 8 weeks (0.015+/-0.017) than the baseline (0.029+/
      0.022), although it was not statistically significant (P=.101). CONCLUSION:
      Ovariectomy induced detectable decrease in second wash-in phase of contrast agent
      into lumbar disc.

PMID- 22459442
TI  - Role of apparent diffusion coefficient values for the differentiation of viable
      and necrotic areas of breast cancer and its potential utility to guide voxel
      positioning for MRS in the absence of dynamic contrast-enhanced MRI data.
AB  - We carried out retrospective analysis of apparent diffusion coefficient (ADC)
      values in 48 infiltrating ductal breast cancer patients who had dynamic contrast
      enhanced magnetic resonance imaging (DCEMRI; Group I) and in 53 patients (Group
      II) for whom DCEMRI data were not available. Twenty-three patients of Group I
      showed no necrosis (Group Ia), while in 25 patients, both viable (nonnecrotic)
      and necrotic tumor areas (Group Ib) were observed on DCEMRI. T1-weighted, fat
      suppressed and short inversion recovery images were used to identify the viable
      and necrotic tumor areas in Group II patients, and necrosis was not seen in 11
      patients (Group IIa), while 42 (Group IIb) showed both viable and necrotic tumor
      areas. The ADCs of the necrotic area of Group Ib (1.79+/-0.30 *10(-3) mm(2)/s)
      and Group IIb (1.83+/-0.40 *10(-3) mm(2)/s) patients were similar and
      significantly higher (P<.01) compared to the ADCs of the viable tumor area of
      Group Ia (0.96+/-0.21 *10(-3) mm(2)/s) and Group IIa (0.90+/-0.17 *10(-3)
      mm(2)/s) patients. Proton MR spectroscopy (MRS) data were also available in these
      patients, and the ADC values were retrospectively determined from the voxel from
      which MR spectrum was obtained. These values were compared with the ADC obtained
      for the viable and necrotic areas of the tumor. ADC of the MRS voxel was similar
      to that obtained for the viable tumor area in patients of both groups. This
      interesting observation reveals the potential utility of using ADC values to
      identify viable tumor area for positioning of voxel for MRS in the absence of
      DCEMRI data.

PMID- 22459443
TI  - A novel content-based active contour model for brain tumor segmentation.
AB  - Brain tumor segmentation is a crucial step in surgical and treatment planning.
      Intensity-based active contour models such as gradient vector flow (GVF), magneto
      static active contour (MAC) and fluid vector flow (FVF) have been proposed to
      segment homogeneous objects/tumors in medical images. In this study, extensive
      experiments are done to analyze the performance of intensity-based techniques for
      homogeneous tumors on brain magnetic resonance (MR) images. The analysis shows
      that the state-of-art methods fail to segment homogeneous tumors against similar
      background or when these tumors show partial diversity toward the background.
      They also have preconvergence problem in case of false edges/saddle points.
      However, the presence of weak edges and diffused edges (due to edema around the
      tumor) leads to oversegmentation by intensity-based techniques. Therefore, the
      proposed method content-based active contour (CBAC) uses both intensity and
      texture information present within the active contour to overcome above-stated
      problems capturing large range in an image. It also proposes a novel use of Gray
      Level Co-occurrence Matrix to define texture space for tumor segmentation. The
      effectiveness of this method is tested on two different real data sets (55
      patients - more than 600 images) containing five different types of homogeneous,
      heterogeneous, diffused tumors and synthetic images (non-MR benchmark images).
      Remarkable results are obtained in segmenting homogeneous tumors of uniform
      intensity, complex content heterogeneous, diffused tumors on MR images (T1
      weighted, postcontrast T1-weighted and T2-weighted) and synthetic images (non-MR
      benchmark images of varying intensity, texture, noise content and false edges).
      Further, tumor volume is efficiently extracted from 2-dimensional slices and is
      named as 2.5-dimensional segmentation.

PMID- 22459444
TI  - Edge-enhanced spatiotemporal constrained reconstruction of undersampled dynamic
      contrast-enhanced radial MRI.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (MRI) is a technique used to
      study and track contrast kinetics in an area of interest in the body over time.
      Reconstruction of images with high contrast and sharp edges from undersampled
      data is a challenge. While good results have been reported using a radial
      acquisition and a spatiotemporal constrained reconstruction (STCR) method, we
      propose improvements from using spatially adaptive weighting and an additional
      edge-based constraint. The new method uses intensity gradients from a sliding
      window reference image to improve the sharpness of edges in the reconstructed
      image. The method was tested on eight radial cardiac perfusion data sets with 24
      rays and compared to the STCR method. The reconstructions showed that the new
      method, termed edge-enhanced spatiotemporal constrained reconstruction, was able
      to reconstruct images with sharper edges, and there were a 36%+/-13.7% increase
      in contrast-to-noise ratio and a 24%+/-11% increase in contrast near the edges
      when compared to STCR. The novelty of this paper is the combination of spatially
      adaptive weighting for spatial total variation (TV) constraint along with a
      gradient matching term to improve the sharpness of edges. The edge map from a
      reference image allows the reconstruction to trade-off between TV and edge
      enhancement, depending on the spatially varying weighting provided by the edge
      map.

PMID- 22459445
TI  - Expediting return of bowel function after colorectal surgery.
AB  - BACKGROUND: Postoperative ileus is the main determinant of the length of hospital
      stay after colorectal surgery. Our objective was to analyze modifiable factors,
      including polyethylene glycol administration, associated with the return of bowel
      function. METHODS: A retrospective review of all patients who underwent elective
      open partial colectomy from 2004 to 2006 at a single institution. RESULTS: The
      time to the first bowel movement with and without oral intake within 48 hours
      postoperatively was 76 hours versus 134 hours (P < .001); with and without
      polyethylene glycol administration it was 73 hours versus 94 hours (P = .001);
      and with and without frequent ambulation it was 78 hours versus 95 hours (P =
      .012). With postoperative nasogastric tube drainage, the time to the first bowel
      movement was 22 hours longer (P = .002). CONCLUSIONS: These data confirm previous
      findings supporting no nasogastric tube drainage, early feeding, and frequent
      ambulation after colorectal surgery. Additionally, our data suggest a strong
      association (P = .001) between the use of polyethylene glycol and the early
      return of bowel function.

PMID- 22459446
TI  - Laparoscopic surgical exploration is an effective strategy for locating occult
      primary neuroendocrine tumors.
AB  - BACKGROUND: Many patients with neuroendocrine tumors (NETs) have metastases at
      diagnosis. Despite extensive metastases the primary tumors remain small and
      difficult to locate. METHODS: Records of patients diagnosed with metastatic
      abdominal NETs from 2006 to 2010 were reviewed retrospectively. Results of
      preoperative imaging, procedures, and surgical explorations were compared for
      their efficacy at finding primary tumors. RESULTS: Sixty-three patients were
      identified. Seventeen percent (11 of 63) of tumors were located by preoperative
      testing. The sensitivities of preoperative colonoscopy (23% [n = 26]), computed
      tomography scan (6.7% [n = 60]), and somatostatin receptor scintigraphy (2.0% [n
      = 52]) were low. No tumors were found by magnetic resonance imaging (n = 9),
      upper endoscopy (n = 24), capsule endoscopy (n = 2), or bronchoscopy (n = 4).
      Surgical exploration was the most sensitive (79% [n = 63]) method of tumor
      detection. Seventy-two percent of surgical localizations were laparoscopic.
      CONCLUSIONS: Surgical exploration was superior to all other modalities for
      locating primary NETs. Laparoscopy had a high probability of finding occult
      primary neuroendocrine tumors.

PMID- 22459447
TI  - Outcomes associated with type of intervention and timing in complex pediatric
      empyema.
AB  - BACKGROUND: The presence of effusion/empyema in pediatric pneumonia can increase
      treatment complexity by possibly requiring pleural drainage. Currently, no data
      support the superiority of any drainage modalities in children. METHODS: We
      performed a retrospective cohort study using the Pediatric Health Information
      System database from 2003 to 2008. RESULTS: A total of 14,936 children were
      hospitalized with effusion/empyema. Fifty-two percent of children were treated
      with antibiotics alone. Compared with patients receiving a chest tube, patients
      receiving antibiotics alone, thoracotomy, and video-assisted thoracoscopic
      surgery had a shorter length of stay, lower mortality rates, and fewer re
      interventions. Delaying drainage by 1 to 3 days was associated with a lower
      mortality rate, and a delay of more than 7 days was associated with a higher
      mortality rate. CONCLUSIONS: Half of all children with effusion/empyema are
      treated with antibiotics alone with low morbidity and mortality. Initial video
      assisted thoracoscopic surgery or thoracotomy had improved outcomes compared with
      other interventions. Intervention should not be delayed beyond 7 days.

PMID- 22459448
TI  - A brief intervention reduces hazardous and harmful drinking in emergency
      department patients.
AB  - STUDY OBJECTIVE: Brief interventions have been shown to reduce alcohol use and
      improve outcomes in hazardous and harmful drinkers, but evidence to support their
      use in emergency department (ED) patients is limited. The use of research
      assessments in studies of brief interventions may contribute to uncertainty about
      their effectiveness. Therefore we seek to determine (1) if an emergency
      practitioner-performed Brief Negotiation Interview or a Brief Negotiation
      Interview with a booster reduces alcohol consumption compared with standard care;
      and (2) the impact of research assessments on drinking outcomes using a standard
      care-no-assessment group. METHODS: We randomized 889 adult ED patients with
      hazardous and harmful drinking. A total of 740 received an emergency practitioner
      performed Brief Negotiation Interview (n=297), a Brief Negotiation Interview with
      a 1-month follow-up telephone booster (Brief Negotiation Interview with booster)
      (n=295), or standard care (n=148). We also included a standard care with no
      assessments (n=149) group to examine the effect of assessments on drinking
      outcomes. Primary outcomes analyzed with mixed-models procedures included past 7
      day alcohol consumption and 28-day binge episodes at 6 and 12 months, collected
      by interactive voice response. Secondary outcomes included negative health
      behaviors and consequences collected by telephone surveys. RESULTS: The reduction
      in mean number of drinks in the past 7 days from baseline to 6 and 12 months was
      significantly greater in the Brief Negotiation Interview with booster (from 20.4
      [95% confidence interval {CI} 18.8 to 22.0] to 11.6 [95% CI 9.7 to 13.5] to 13.0
      [95% CI 10.5 to 15.5]) and Brief Negotiation Interview (from 19.8 [95% CI 18.3 to
      21.4] to 12.7 [95% CI 10.8 to 14.6] to 14.3 [95% CI 11.9 to 16.8]) than in
      standard care (from 20.9 [95% CI 18.7 to 23.2] to 14.2 [95% CI 11.2 to 17.1] to
      17.6 [95% CI 14.1 to 21.2]). The reduction in 28-day binge episodes was also
      greater in the Brief Negotiation Interview with booster (from 7.5 [95% CI 6.8 to
      8.2] to 4.4 [95% CI 3.6 to 5.2] to 4.7 [95% CI 3.9 to 5.6]) and Brief Negotiation
      Interview (from 7.2 [95% CI 6.5 to 7.9] to 4.8 [95% CI 4.0 to 5.6] to 5.1 [95% CI
      4.2 to 5.9]) than in standard care (from 7.2 [95% CI 6.2 to 8.2] to 5.7 [95% CI
      4.5 to 6.9] to 5.8 [95% CI 4.6 to 7.0]). The Brief Negotiation Interview with
      booster offered no significant benefit over the Brief Negotiation Interview
      alone. There were no differences in drinking outcomes between the standard care
      and standard care-no assessment groups. The reductions in rates of driving after
      drinking more than 3 drinks from baseline to 12 months were greater in the Brief
      Negotiation Interview (38% to 29%) and Brief Negotiation Interview with booster
      (39% to 31%) groups than in the standard care group (43% to 42%). CONCLUSION:
      Emergency practitioner-performed brief interventions can reduce alcohol
      consumption and episodes of driving after drinking in hazardous and harmful
      drinkers. These results support the use of brief interventions in ED settings.

PMID- 22459449
TI  - Characterization of Dkk1 gene regulation by the osteoblast-specific transcription
      factor Osx.
AB  - Bone formation is a developmental process involving the differentiation of
      mesenchymal stem cells to osteoblasts. Osterix (Osx) is an osteoblast-specific
      transcription factor required for bone formation and osteoblast differentiation.
      Previous observation that Osx inhibits Wnt signaling pathway provides a novel
      concept of feedback control mechanisms involved in bone formation. Wnt antagonist
      Dickkopf-1 (Dkk1) plays an important role on skeletal development and bone
      remodeling. Osx has been shown to activate the Dkk1 promoter; however, the
      detailed mechanism of Osx regulation on Dkk1 expression is not fully understood.
      In this study, quantitative real-time RT-PCR results demonstrated that Dkk1
      expression was downregulated in Osx-null calvaria at two different points of
      E15.5 and E18.5 in mice embryos. Overexpression of Osx resulted in upregulation
      of Dkk1 expression in Tet-off stable C2C12 cell line. Inhibition of Osx
      expression by siRNA led to downregulation of Dkk1 in osteoblasts. These data
      suggest that Osx may target Dkk1 directly. To define minimal region of Dkk1
      promoter activated by Osx, we made a series of deletion mutants of Dkk1 promoter
      constructs, and narrowed down the minimal region to the proximal 250bp by
      transient transfection assay. It was shown that two GC-rich binding sites within
      this minimal region of Dkk1 promoter were required for the Dkk1 promoter
      activation by Osx. Importantly, quantitative chromatin immunoprecipitation (ChIP)
      assays were performed to show that endogenous Osx associated with native Dkk1
      promoter in primary osteoblasts. Taken together, these findings support our
      hypothesis that Dkk1 is a direct target of Osx.

PMID- 22459450
TI  - MicroRNA-320a suppresses human colon cancer cell proliferation by directly
      targeting beta-catenin.
AB  - Recent profile studies of microRNA (miRNA) expression have documented a
      deregulation of miRNA (miR-320a) in human colorectal carcinoma. However, its
      expression pattern and underlying mechanisms in the development and progression
      of colorectal carcinoma has not been elucidated clearly. Here, we performed real
      time PCR to examine the expression levels of miR-320a in colon cancer cell lines
      and tumor tissues. And then, we investigated its biological functions in colon
      cancer cells by a gain of functional strategy. Further more, by the combinational
      approaches of bioinformatics and experimental validation, we confirmed target
      associations of miR-320a in colorectal carcinoma. Our results showed that miR
      320a was frequently downregulated in cancer cell lines and colon cancer tissues.
      And we demonstrated that miR-320a restoration inhibited colon cancer cell
      proliferation and beta-catenin, a functionally oncogenic molecule was a direct
      target gene of miR-320a. Finally, the data of real-time PCR showed the reciprocal
      relationship between miR-320a and beta-catenin's downstream genes in colon cancer
      tissues. These findings indicate that miR-320a suppresses the growth of colon
      cancer cells by directly targeting beta-catenin, suggesting its application in
      prognosis prediction and cancer treatment.

PMID- 22459451
TI  - The differentiating and apoptotic effects of 2-aza-5'-deoxycytidine are dependent
      on the PU.1 expression level in PU.1-transgenic K562 cells.
AB  - The use of 5-aza-2'-deoxycytidine (5-azadc) for myelodysplastic syndrome, acute
      myeloid leukemia and chronic myeloid leukemia is becoming an effective and
      attractive option for these hematological malignancies. The PU.1 transcription
      factor is important for cellular differentiation through the control of its
      target genes not only in myeloid and B-lymphoid cells, but also in erythroid
      cells. Downregulation of PU.1 was reported to play a role in the pathogenesis of
      various hematological malignancies. In this study, we sought to identify the
      relationship between the effects of 5-azadc and PU.1. For this purpose, we
      employed PU.1-knockdown K562 (K562 PU.1KD) cells stably expressing PU.1 short
      inhibitory RNAs and PU.1-overexpressing K562 (K562 PU.1OE) cells. Therapeutic
      concentrations (0.1 and 0.5 MUM) of 5-azadc resulted in growth arrest in the G2/M
      phase. Strikingly, however, K562 PU.1OE cells had significantly increased rates
      of G2/M and apoptotic sub-G1 phase cells. We observed the induction of cyclin B1,
      a regulator of the G2/M transition, after the addition of 5-azadc. This induction
      was abolished in K562 PU.1KD cells, but significantly induced in K562 PU.1OE
      cells. Further analyses revealed potent induction of hemoglobin A1 expression in
      K562 PU.1OE cells. Taken together, these findings suggest that the PU.1
      expression level is tightly related to the differentiating and apoptotic effects
      of 5-azadc in K562 cells.

PMID- 22459452
TI  - Effect of aceclofenac on pharmacokinetic of phenytoin.
AB  - Aceclofenac is presently most commonly prescribed analgesic for chronic pain and
      inflammatory conditions. In clinical practice, phenytoin and aceclofenac are used
      in a chronic condition of generalized seizure with concomitant chronic pain.
      Hence there are chances of drug-drug interaction because modulations of
      isoenzymes involved in metabolism of phenytoin and aceclofenac are CYP2C9/10 and
      CYP2C19. It is important to maintain the therapeutic level of phenytoin in plasma
      for effective control of seizure. So, the aim of the study was to determine the
      effect of aceclofenac on the pharmacokinetics of phenytoin in rabbits. In a
      parallel design study, phenytoin 30 mg/kg/day per oral was given daily for seven
      days. On day 7, blood samples were taken at various time intervals between 0-24
      hours. In aceclofenac group, phenytoin was administered for seven days as above.
      On day 8, aceclofenac 14 mg/kg along with phenytoin 30 mg/kg/day was administered
      and blood samples drawn as above. Plasma phenytoin levels were assayed by HPLC
      and pharmacokinetic parameters were calculated. In aceclofenac group, there was
      decrease in t1/2el than phenytoin group significant changes were observed in the
      pharmacokinetic parameters in aceclofenac treated group. These results suggest
      that aceclofenac alter the pharmacokinetics of phenytoin. Confirmation of these
      results in human studies will warrant changes in phenytoin dose or frequency when
      aceclofenac is co-administered with it.

PMID- 22459453
TI  - Comparison of bioavailability and pharmacokinetics of diclofenac sodium and
      diclofenac potassium in normal and alloxan-diabetic rabbits.
AB  - The present study was undertaken to compare the bioavailability and
      pharmacokinetic parameters of diclofenac sodium and diclofenac potassium in
      normal and experimentally induced diabetic state in 24 rabbits using a validated
      reversed phase HPLC method with a washout period of one week.Biochemical and
      physiological parameters were measured in normal and diabetic rabbits. Primary
      kinetic parameters i.e. AUC(0-oo), C(max), t(max) and other disposition kinetics
      were determined with non-compartmental procedure.  A paired t-test for normal and
      alloxan treated rabbits revealed a significant decrease in packed cell volume and
      a significant increase in glucose, total lipids, total proteins, albumin and
      globulin were observed in diabetic (metabolically altered) rabbits. Plasma
      concentration of diclofenac (sodium) and diclofenac (potassium) decreased in
      diabetic condition. Significantly high concentration of diclofenac (potassium)
      was observed in normal and diabetic conditions as compared to diclofenac
      (sodium). The variation in bioavailability and disposition of diclofenac sodium
      and diclofenac potassium in diabetic state will require adjustment of the dosage
      regimen prescribed for diabetics in clinical setting.

PMID- 22459454
TI  - Biological screening of Scrophularia nodosa extract and its fractions.
AB  - Biological screening of Scrophularia nodosa crude extract and its fractions
      (hexane, chloroform, ethyl-acetate, n-butanol and aqueous) was carried out on
      phytotoxicity, cytotoxicity, antibacterial, antifungal and analgesic activities.
      Crude extract and its fractions produced 50-100% phytotoxicity at 1000MU/mL
      concentration whereas 25-77% phytotoxicity was observed at 10MU/mL concentration.
      The fractions exhibited significant antibacterial and antifungal effects. The non
      toxic results of this plant were recorded in Brine Shrimps Bioassay method at all
      concentrations. Similarly no significant insecticidal activity was observed in
      crude extracts and fractions. Analgesic activity results of S. nodosa in mice
      were found highly significant in crude extract as compared to fractions. In
      writhing test crude extract at 500 mg/kg showed 65.6% highest inhibitory response
      in mice.

PMID- 22459455
TI  - Terpenoids from Juniperus procera with hepatoprotective activity.
AB  - The petroleum ether fraction of Juniperus procera showed significant activity as
      hepatoprotective when investigated against carbon tetrachloride induced liver
      injury. The hepatoprotective activity was evaluated through the quantification of
      biochemical parameters and confirmed using histopathology analysis. Phytochemical
      investigation of the petroleum ether fraction utilizing different chromatographic
      techniques resulted in the isolation of six known diterpenoids namely: 4-epi
      abietol (1), ferruginol (2), hinokiol (3), sugiol (4), Z-communic acid (5) and
      hinokiol-1-one 3beta,12-dihydroxyabieta-8,11,13-triene-1-one) (6), in addition to
      the sesquiterpene 8alpha-acetoxyelemol (7). Both physical and spectral data were
      used for structure determination and all isolates were evaluated for their
      hepatoprotective activity. Compounds 1 and 4 were the most effective in reducing
      the elevated liver enzymes as indication for liver protection.

PMID- 22459456
TI  - Teratogenic effect of lead acetate on Bactrocera dorsalis and Bactrocera zonata.
AB  - Bactrocera dorsalis and Bactrocera zonata were studied under the effect of lead
      acetate for 48 hours exposure at larval stages. Since, lead is widely distributed
      industrial pollutant in the world. It is significant environmental pollutant
      which contaminates foods, water, soil and air and insect could get easily the
      influence of such pollutants. Therefore, the teratogenic effects of lead (lead
      acetate) on external morphology on fruit flies was determined. The effects of
      lead acetate, in the concentrations of 0.125 mg., 0.25 mg., 0.5 mg, 1.0 mg and
      2.0 mg on Bactrocera dorsalis, Bactrocera zonata, were studied at 48 hours post
      treatment. It was observed that under the effects of lead abnormalities and
      malformation were developed in the larvae of flies. Teratomorphic changes were
      observed as elongated wings, de-shaped wings, elongated and folded legs, change
      in melanization of larvae, pupae and adults. Some other structural abnormalities
      of larvae and pupal shape were also observed. Thus, the Diptera flies could
      present a useful module for the rapid screening of the environmental hazards due
      to lead contamination, which exerts a definite physiological and morphological
      effect on Diptera flies. Therefore, in this respect Bactrocera dorsalis,
      Bactrocera zonzta, could be included in a test system for heavy metals toxicity
      determination.

PMID- 22459457
TI  - Hypolipidemic effect of aqueous extract of Carum carvi (black Zeera) seeds in
      diet induced hyperlipidemic rats.
AB  - Medicinal plants play a key role in preventing various diseases. Hyperlipidemia
      is a major contributor to the pathogenesis of cardiovascular diseases. The
      purpose of the present study was to assess the effect of aqueous extract of Carum
      carvi seeds in diet induced hyperlipidemia in rats. 2% cholesterol diet were
      given to rats for six weeks and rats showed high lipid levels were included in
      the study. Then all rats were divided into, normal control group (A),
      hyperlipidemia positive control group (B), and the remaining two groups (C and D)
      served as experimental groups. Group C hyperlipidemic experimental rats received
      aqueous dried extract of Carum carvi seeds at 60 mg/kg of body weight for eight
      weeks on daily basis. On the other hand group D rats received simvastatin at 1.0
      mg/kg body weight for eight weeks. Blood samples were collected after eight
      weeks. The hyperlipidemic positive control group rats showed variable increase in
      serum triglycerides, LDL and total cholesterol levels. Serum HDL levels decreased
      in hyperlipidemic positive control groups. Carum carvi and simvastatin
      significantly decreased the levels of these parameters in rats. On comparison
      Carum carvi reduced lipid levels more, effectively than the simvastatin. Carum
      carvi constituents, especially flavonoids and carvone have strong anti-oxidant
      activity which might be involved in hypolipidemia. In conclusion, Carum carvi
      aqueous seeds extract decrease lipid levels in diet induced hyperlipidemic rats.

PMID- 22459458
TI  - Drug utilization evaluation of third generation cephalosporins using core drug
      use indicators.
AB  - To evaluate the drug utilization of third generation cephalosporins using core
      drug use indicators in various wards of Sri Ramachandra Hospital. Third
      generation cephalosporins are the most commonly prescribed broad spectrum
      antibiotic even before the culture sensitivity results arrives. Hence this study
      was undertaken to study the drug utilization evaluation of third generation
      cephalosporins in the inpatient department of various wards of Sri Ramachandra
      Hospital. A prospective study was conducted between July 2009 and February 2010.
      Prescriptions of 364 patients containing third generation cephalosporins admitted
      in inpatient department of various wards of Sri Ramachandra Hospital, Chennai
      were collected and using WHO basic drug indicators, the utilization pattern were
      analyzed. The average number of drugs per prescription was found to be 7.89 on
      prescription analysis. Cefixime was the most frequently prescribed (32.69%) oral
      third generation cephalosporins, followed by cefotaxime (31.32%). Among IV third
      generation cephalosporins, cefotaxime was the most frequently prescribed
      injections (35.4%). Only 28.02% of drugs were prescribed by generic name. The
      results obtained represent the over all prescribing pattern of third generation
      cephalosporins in the Tertiary Care Teaching Hospital, Chennai.

PMID- 22459459
TI  - Quantitative determination of deferiprone in human plasma by reverse phase high
      performance liquid chromatography and its application to pharmacokinetic study.
AB  - Deferiprone (1, 2 dimethyl-3-hydroxypyrid-4-one) is considered to be the standard
      iron chelator. Pharmacokinetic studies of generic formulations are required in
      local condition before placed on the market. High performance liquid
      chromatographic (HPLC) method was used for quantification of deferiprone in human
      plasma using UV/VIS detector. Chromatographic separation was carried out on C(18)
      column, with a mobile phase of methanol-buffer (18:82, v/v), pH 3.5, and caffeine
      was used as an internal standard. The calibration curve was linear over the range
      0.25-10 MUg/mL in human plasma (R(2) = 0.9994). After oral administration of
      deferiprone (500 mg) to human, the plasma concentration-time curve of deferiprone
      was conformed to two-compartment open model. The deferiprone plasma concentration
      showed a rapid absorption and average area under the plasma concentration-time
      curve (AUC) of deferiprone was 17.0 +/- 1.23 h.MUg/ml. Average absorption and
      elimination half-life values of deferiprone of 24 volunteers were 0.62 +/- 0.12
      and 2.65 +/- 0.43 hours. This study confirms the rapid absorption of deferiprone
      in humans. AUC was similar to that previously reported but C(max) was slightly
      lower than that stated in the literature.

PMID- 22459460
TI  - A PCR-RFLP based protocol for the detection of hepatitis B virus variants in some
      lamivudine-untreated chronic hepatitis B virus carriers in Pakistan.
AB  - Hepatitis B virus (HBV) affects more than 350 million people worldwide and is a
      leading cause of morbidity and mortality in developing countries like Pakistan.
      Lamivudine has potential to inhibit hepatitis B virus (HBV) replication but long
      term lamivudine treatment results in mutations in YMDD region of HBV, making this
      therapy ineffective. In this study, we have optimized a polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) based protocol to detect two
      mutations in HBV DNA polymerase gene (at codon 528 and 552) in chronic hepatitis
      patients, without any prior lamivudine treatment. HBV genome was extracted and
      tested by PCR-RFLP for detection of mutations in polymerase gene. Variations in
      HBV genome were not detected in enrolled patients confirming that lamivudine can
      be used to treat chronic Hepatitis B in these patients. Several studies have
      reported the natural occurrence of mutation in YMDD motif of polymerase gene in
      chronic hepatitis B patients, not treated with lamivudine, but these mutants were
      not detected in Pakistani lamivudine-untreated chronic hepatitis B patients.

PMID- 22459461
TI  - Anticancer activities of constituents from the stem of Polyalthia rumphii.
AB  - Nine known compounds were firstly isolated from the chloroform extract of
      Polyalthia rumphii stem by anticancer activity guidance, and the chemical
      structures were identified by using spectroscopic and physico-chemical analysis.
      Cytotoxic evaluation against four cancer cell lines was performed on all these
      compounds, which showed that K562 could be significantly inhibited by partial
      compounds with IC(50) values at the range from 40 to 60 MU/mL.

PMID- 22459462
TI  - In vitro assessment of relief to oxidative stress by different fractions of
      Boerhavia procumbens.
AB  - Methanolic extract of Boerhavia procumbens Bank ex Roxb. was partitioned with n
      hexane, chloroform, ethyl acetate and n-butanol sequentially after dissolving in
      distilled water. Phytochemical screening showed presence of phenolics,
      flavonoides and cardiac glycosides in large amount in chloroform, ethyl acetate
      and n-butanol soluble fraction. The antioxidant activity of all these fractions
      and the remaining aqueous fraction was evaluated by four methods such as: 1,1
      diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, ferric
      reducing antioxidant power (FRAP) assay, total antioxidant activity and ferric
      thiocyanate assay. Total phenolics were also determined. Some fractions showed
      noteworthy antioxidant activity. The results of the antioxidant activity revealed
      that the ethyl acetate soluble fraction showed the highest value of percent
      inhibition of DPPH (82.54 +/- 0.62) at the concentration of 125 MU g/ml. The
      IC(50) of this fraction was 37.11+/- 0.23 MUg/ml, compared with butylated
      hydroxytoluene (BHT), which have IC(50) of 12.1 +/- 0.92 MU/mL. It also showed
      the highest FRAP value (251.08 +/- 1.46 MUg of trolox equivalents) as well as the
      highest value of lipid peroxidation inhibition (57.21 +/- 52%), the highest total
      antioxidant activity (0.549 +/- 0.08) and also the highest total phenolic
      contents (77.1 +/- 0.6) as compared to the studied fractions. Phytochemical
      screening showed high percentage of phenolics, flavonoides and cardiac glycosides
      in this fraction.

PMID- 22459463
TI  - Effect of olive oil on transdermal penetration of flurbiprofen from topical gel
      as enhancer.
AB  - The present study was conducted to formulate and evaluate flurbiprofen
      transdermal gel. A standard calibration curve was constructed to obtain a
      regression line equation to be used for finding out the concentration of drug in
      samples. Olive oil was used as penetration enhancer and was added in different
      concentrations to some selected formulations to see its enhancement effect on in
      vitro drug release profiles. The prepared gels were evaluated for several physico
      chemical parameters to justify their suitability for topical use. The in vitro
      drug release studies were carried out by using Franz cell diffusion apparatus
      across both synthetic membrane and excised albino rabbit skin. In order to
      investigate the drug release mechanism a kinetic approach was made by employing
      Korsmeyer kinetic model to the in vitro drug release profiles of flurbiprofen.
      The flurbiprofen topical gels were successfully prepared and could be beneficial
      for topical use.

PMID- 22459464
TI  - Development and validation of a stability indicating HPLC method for the analysis
      of lornoxicam in powder for injection.
AB  - A rapid, isocratic stability indicating high performance liquid chromatographic
      method was developed and validated for the estimation of lornoxicam in its powder
      for injection. The analysis was performed on a Shimadzu VP-ODS (4. 6 mm x 15 cm,
      5 um) column. The mobile phase consisted of sodium acetate (pH 5.8; 0.05 M) and
      methanol (45:55) flowed at 1.0 ml/min. Detection was carried out at 290 nm. The
      developed method had the good ability to separate lornoxicam well from the
      degradation products. The regression data showed good linear relationship at the
      concentration range of 4.04-20.20 MU/mL with r(2)=0.9999. Specificity, linearity,
      accuracy, precision and robustness of the method were evaluated to validate the
      proposed method. Stressed degradation studies were conducted to provide an
      indication of its stability indicating property. The limits of detection and
      quantitation were 9.70 and 33.94 ng /ml, respectively. Lornoxicam was found to be
      stable in the mobile phase in 24 h. The co-existed excipients had no interference
      with the analytical procedure. Additional peaks appeared in the chromatograms of
      five kinds of forced degraded samples (light, heat, acid, base and oxidation
      degradation). Mean recovery assessed at three levels was from 99. 7 to 100.3%,
      indicating the good accuracy of the method. Repeatability and inter-day RSD of
      the method was determined to be 0.38% and 0.81%, respectively. The HPLC method
      was demonstrated to be robust for intentional minor changes of ratio, pH change,
      salt concentration and column temperature. The method should be utilized as the
      routine analysis and quality control of lornoxicam in injectable formulation.

PMID- 22459465
TI  - Comparative evaluation of some commercially available brands of pharmaceutical
      preparations for Na, K and Mg concentrations.
AB  - A study was carried out to investigate the concentrations of macro-elements
      (Na(+), K(+) and Mg(+2)) in twelve commercially available pharmaceutical
      preparations used as sex stimulant, by Atomic Absorption Spectrophotometer. A wet
      digestion method was adopted to prepare the samples. The results indicated that
      sodium concentration was maximum (3702 +/- 29 MUg g(-1)) in LB and minimum (495
      +/- 06 MUg g(-1)) in H-E-H. Potassium concentration was maximum (6337 +/- 13 MUg
      g(-1)) in NBA while minimum (150 +/- 06 MUg g(-1)) in ZGRA. Magnesium
      concentration was maximum in V-100 (9226 +/- 11 MUg g(-1)) and minimum in FGRA
      (1194 +/- 25 MUg g(-1)). The concentration of macro-elements in the imported
      herbal preparations was in the order of Mg<Na<K and in the local herbal
      preparations as follows: Mg<K<Na. Some of these herbal preparations contain high
      level of macro-elements than the recommended daily dietary allowances. The
      excessive use of such preparations may cause severe allergic reactions, kidney
      damage and pulmonary atherosclerosis.

PMID- 22459466
TI  - Synthesis, characterization and biodistribution of novel amine thiophene 99mTc
      labeled complex.
AB  - (99m)Tc-labeled amine thiophene ligand might be a potential candidate for brain
      imaging. The purpose was to investigate the uptake of a radiolabeled drug in the
      brain. In this study, a tetradentate amine-thiophene-dione ligand was synthesized
      by the reaction of thiophene-2-carboxaldehyde with ethane-1,2-diamine and
      reducing with NaBH(4). The ligand system was characterized by elemental analysis,
      FTIR and 1H NMR. Radiolabeling of the complex with (99m)Tc was performed by
      reducing with stannous ions. The radiochemical purity of the radiolabeled drug
      was determined by paper chromatography (PC) and instant thin layer chromatography
      (ITLC). Bioevaluation of the (99m)Tc complex was studied in rabbits. The yield of
      the final product was 4.42 g (60%) and the characterization data confirmed the
      synthesis of the final product. The efficacy of radiolabeling was >98%. A
      significant uptake was observed in the brain which retained significantly upto
      4h. The data indicate that the proposed system may be suitable for brain imaging
      in future clinical applications.

PMID- 22459467
TI  - Simultaneous determination of triacetin, acetic ether, butyl acetate and
      amorolfine hydrochloride in amorolfine liniment by HPLC.
AB  - A simple, rapid, specific and precise reversed-phase high-performance liquid
      chromatographic method was developed for simultaneous estimation of triacetin,
      acetic ether, butyl acetate and amorolfine in marketed pharmaceutical liniment.
      Chromatographic separation was performed on a Shimadzu VP-ODS C(18) column using
      the mixture of citric acid-hydrochloric acid-sodium hydrate buffer (pH 3.0),
      acetonitrile and methanol (32:30:38) as the mobile phase at a flow rate of 1.0
      mL/min with UV-detection at 215 nm. The method separated the four components
      simultaneously in less than 10 min. The validation of the method was performed
      with respect to specificity, linearity, accuracy, and precision. The calibration
      curves were linear in the range of 35.1-81.9 MU/mL for triacetin, 431.1-1005.9
      MU/mL for acetic ether, 167.0-389.7 MU/mL for butyl acetate and 151.0-352.3 MU/mL
      for amorolfine. The mean 100% spiked recovery for triacetin, acetic ether, butyl
      acetate and amorolfine is 99.43 +/- 0.42, 101.5 +/- 1.09, 101.4 +/- 1.02 and
      100.8 +/- 0.69, respectively. The intra-day and inter-day relative standard
      deviation values were <2.0%. The limits of detection of these compounds ranged
      from 0.08 to 5.88 ng. The utility of the procedure was verified by its
      application to the commercial liniment.

PMID- 22459468
TI  - Role of Glutathione in protection against mercury induced poisoning.
AB  - Mercury is harmless in an insoluble form, such as mercuric sulfide, but it is
      poisonous in soluble forms such as mercuric chloride or methylmercury. Mercury is
      a neurotoxin. Outbreaks of mercuric chloride poisonings have made it clear that
      adults, children, and developing fetuses are at risk from ingestion exposure to
      mercury. It is very important and interesting to study the reaction of mercuric
      chloride and Glutathione as biomarker of Glutathione role in detoxification and
      conjugation in components (Plasma and Cytosolic Fraction). The effect of mercuric
      chloride's different concentrations was examined on GSH present in plasma and
      cytosolic fraction. Decrease in GSH level was dependant on mercuric chloride
      concentration. The decrease in GSH level of blood components was more prominent
      with the time of incubation of mercuric chloride. Decrease in the concentration
      of reduced state Glutathione may be due the interaction of reduced state
      Glutathione (GSH) and mercuric chloride to form oxidized Glutathione (GSSG) or
      mercuric-glutathione complex. This change in GSH metabolic status provides
      information regarding the role of GSH in detoxification of mercuric chloride. The
      effect of mercury metal on Glutathione in blood components has been discussed in
      this paper in vitro condition as a model for in Vivo condition.

PMID- 22459469
TI  - Effect of an anti-thyroid drug, 2,8-Dimercapto-6-hydroxy purine on reproduction
      in male rats.
AB  - This histomorphological study is designed to evaluate the peripheral action of
      2,8-Dimercapto-6-hydroxypurine (an antithyroid drug) on male reproductive system.
      The drug was administered as i.p. injection for 21 days to investigate its role
      on morphology of intratesticular cells and plasma testosterone level. Adult male
      rats (n=12), divided into three groups i.e. control, dimethylsulphoxide (DMSO)
      and 2,8-Dimercapto-6-hydroxypurine treated groups and treated with saline, DMSO
      and 2,8-Dimercapto-6-hydroxypurine for 21 consecutive days respectively. Blood
      samples were collected at day 1, 7, 14 and 21 and analyzed by using EIA systems.
      All the animals were scarified on 22nd day and testicular tissues were studied by
      histomorphpological assesment. 2,8-Dimercapto-6-hydroxypurine caused a
      significant decrease (P<0.0001) in mean testicular cell population, testicular
      cell diameter and resulted in arrested spermatogenesis. A significant decrease
      (P<0.0001) was observed in mean Sertoli and Leydig cell population and diameter
      in treated group. Similarly a significant decrease was observed in plasma
      testosterone levels at days 1, 7 and 14 (P<0.05) and further decrease by day 21
      (P<0.01) of drug treatment. The present study suggests that 2,8-Dimercapto-6
      hydroxypurine is a negative modulator of reproductive system as it suppressed the
      plasma testosterone level and proliferation of different testicular cell types in
      adult male rats.

PMID- 22459470
TI  - The effect of hydro alcoholic extract of Juglans regia leaves in streptozotocin
      nicotinamide induced diabetic rats.
AB  - Phytotherapy has been achieved to maintain glycemic control in patients with
      diabetes mellitus. The present study was conducted to evaluate the
      antihyperglycemic properties of the Juglans regia leaf extract in streptozotocin
      nicotinamide induced diabetic rats. Nicotinamide was injected intraperitonealy
      (i.p.) 15 min before the injection of Streptozotocin (i.p.). One week after
      induction of diabetes, oral treatment started with extract of Juglans regia and
      Metformin and continued for 4 weeks. Fasting blood sugar, body weight, serum
      lipids and insulin level were measured in different groups. A significant
      reduction of glucose, HbA1c, total cholesterol and serum triglycerides were
      detected after 4 weeks in rats treated with Juglans regia leaves compared to the
      control groups. Thus, Juglans regia extract treatment showed potential
      hypoglycemic and hypolipidemic effects in type 2 diabetic rats.

PMID- 22459471
TI  - Rapid separation and determination of betulinic acid from a complex matrix using
      combination of TLC and RP-HPLC.
AB  - Hitherto, only a few studies are reported about using the combination of TLC and
      RP-HPLC for the separation and determination of analyte(s) from a complex matrix.
      The present study is aimed to develop a simple and rapid method for the
      separation and determination of betulinic acid from a complex matrix, extracts of
      Orthosiphon stamineus, using a combination of the two techniques. The samples
      having higher contents of the analyte and fewer interfering species were prepared
      using TLC. The samples were then eluted through C(18) column using isocratic
      solvent system comprising acetonitrile, methanol and acetic acid acidified water
      of pH 2.8 in a ratio of 70 : 20 : 10 (v/v/v), respectively, and detection was
      carried out at 210 nm. The method was validated and applied successfully to
      quantify betulinic acid in various types of extracts of the plant. The limit of
      detection (LOD) and limit of quantification (LOQ) were found to be 0.0005 and
      0.0050 MUg/ml, respectively. The method exhibited linearity in a concentration
      range of 0.005-100.00 MUg/ml (R(2)= 0.9999). The recovery was found to be 97.10 -
      97.60% (RSD < 5%), whereas, intra-day and inter-days accuracy values were 97.13 -
      98.67% (RSD < 5%) and 96.45 - 98.00% (RSD < 5%), respectively. The results of the
      present study indicate that the developed method is simple, rapid, sensitive and
      accurate, and may be of a value to natural product industry and researchers for
      the standardization of extracts containing betulinic acid in a lesser time and
      consuming fewer solvents.

PMID- 22459472
TI  - Correction of iron deficiency anemia in pregnancy and its effects on superoxide
      dismutase.
AB  - Iron deficiency anemia (IDA) affects not only the hematological parameters but
      also disturb the oxidative balance of body. In pregnancy, this is much more
      considerable as oxidative stress is considered to be one of the physiological
      changes during this period. This study aims to observe the effect of daily iron
      supplement on oxidative stress in pregnancy. In this study, 30 pregnant women
      with IDA were treated with daily oral iron supplements for 12 weeks. After 12
      weeks hemoglobin (Hb), hematocrit, serum ferritin concentration (SFC) and
      superoxide dismutase (SOD) activity were measured and compared with pre
      supplement levels. A significant increase in all the parameters was observed
      after treatment (p<0.05). When post supplemental values of SFC and SOD were
      compared with control group comprising of 10 non anemic pregnant women, they were
      significantly low (p<0.05). Our results indicate that oxidative stress in
      pregnancy associated with IDA decreases with daily iron supplements but fail to
      reach normal pregnant levels. This supports iron over load theory in daily iron
      supplements and suggests that oxidative stress increases if pregnancy is
      associated with iron deficiency.

PMID- 22459473
TI  - Study of surface activity of piroxicam at the interface of palm oil esters and
      various aqueous phases.
AB  - The surface activity of some non-steroidal anti-inflammatory agents like
      ibuprofen was investigated extensively. This fact has attracted the researchers
      to extend this behavior to other agents like piroxicam. Piroxicam molecules are
      expected to orient at the interface of oil and aqueous phase. The aim of this
      study was, firstly, to assess the surface and interfacial tension behaviour of
      newly synthesised palm oil esters and various pH phosphate buffers. Furthermore,
      the surface and interfacial tension activity of piroxicam was studied. All the
      measurements of surface and interfacial tension were made using the tensiometer.
      The study revealed that piroxicam has no effect on surface tension values of all
      pH phosphate buffers and palm oil esters. Similarly, various concentrations of
      piroxicam did not affect the interfacial tensions between the oil phase and the
      buffer phases. Accordingly, the interfacial tension values of all mixtures of oil
      and phosphate buffers were considerably high which indicates the immiscibility.
      It could be concluded that piroxicam has no surface activity. Additionally, there
      is no surface pressure activity of piroxicam at the interface of plam oil esters
      and phosphate buffers in the presence of Tweens and Spans.

PMID- 22459474
TI  - Inhibitory effects of the volatile oils of Callistemon citrinus (Curtis) Skeels
      and Eucalyptus citriodora Hook (Myrtaceae) on the acetylcholine induced
      contraction of isolated rat ileum.
AB  - Using steam distillation method, the volatile oils of Eucalyptus citriodora and
      Callistemon citrinus were obtained and their chromatographic profiles examined in
      hexane: ethylacetate (4:1; 7:3) and hexane-chloroform (7:3). The effects of the
      volatile oils on acetylcholine (Ach) induced contraction of the rat isolated
      ileum were investigated based on the ethnomedicinal use of the volatile oil of E.
      citriodora in treating diarrhoea. Relative to the weight of the fresh leaves
      (200g in each case), E. citriodora produced 0.75% of the volatile oil while the
      C. citrinus yielded 0.5%. Combination of hexane-ethylacetate (4:1) gave the best
      resolution of the constituents as E. citriodora produced six major spots while
      Callistemon citrinus produced three. The concentration-dependent contractions of
      the ileum produced by the increasing concentration of the Ach were observed to be
      remarkably attenuated in the presence of the volatile oils at 5 and 10 mg/ml. At
      5mg/ ml, the volatile oils of E. citriodora and C. citrinus independently reduced
      the Ach maximum contraction to 74.11 +/- 12.4 and 19.05 +/- 5.17% respectively.
      At 10mg/ml, the volatile oils further significantly (P<0.05) inhibited the
      contraction induced by the Ach. The results obtained validated the ethnomedicinal
      use of the volatile oils particularly that of E. citriodora in reducing ilea
      contractions occasioned by diarrhoea. However, C. citrinus volatile oil seems to
      be more effective.

PMID- 22459475
TI  - Comparison of monoamine reuptake inhibitors for the immobility time and serotonin
      levels in the hippocampus and plasma of sub-chronically forced swim stressed
      rats.
AB  - The current study was aimed at comparing the behavioral and biochemical (5
      hydroxytryptamine and 5-hydroxyindoleacetic acid levels) effects of monoamine
      reuptake inhibitors (fluoxetine, venlafaxine and imipramine) in sub-chronically
      forced swim stressed rats. At the given doses of 10, 20 and 30 mg/kg, among
      aforesaid antidepressants, the imipramine treatment alone caused significant
      decline in the immobility time of rats (IC(50)  20 mg/kg). In the hippocampus of
      rats, the imipramine treatment caused significant elevation of 5
      hydroxytryptamine (5-HT) whereas, the fluoxetine and venlafaxine elicited
      significant increase in 5-hydroxyindoleacetic acid (5-HIAA) levels. Likewise, in
      the plasma of rats, the imipramine treatment significantly increased the 5-HIAA
      levels whereas, the fluoxetine and venlafaxine treatment significantly elevate
      the 5-HT levels. It can therefore be inferred that the imipramine did not act
      like other monoamine reuptake inhibitors in biochemical study, which could
      possibly underlie its ability to be detected in forced swim test (behavioral
      study). Moreover, the re-uptake inhibition of 5-HT is not accountable for the
      antidepressant action exhibited in forced swim test.

PMID- 22459476
TI  - Improved physicochemical characteristics of artemisinin-nicotinamide solid
      dispersions by solvent evaporation and freeze dried methods.
AB  - Artemisinin (ARMN) is a drug of choice against drug-resistant malaria especially
      due to Plasmodium falciparum. Being poorly soluble in water, its solid
      dispersions with nicotinamide (NA) were prepared at various drug-carrier ratios
      (1:1, 1:4, 1:6, 1:8, 1:10) by solvent evaporation and freeze drying methods.
      These solid dispersions were characterized by differential scanning calorimetery
      (DSC), fourier transform infrared spectroscopy (FTIR), X-ray diffraction patterns
      (XRD), phase solubility and dissolution studies. Artemisinin and nicotinamide
      both were found completely crystalline as shown by their XRD patterns. Physical
      mixtures (PMs) showed decreased intensity in their XRD patterns while solid
      dispersions by solvent evaporation method (SLVPs) exhibited displaced angles and
      decreased intensity whereas freeze dried solid dispersions (FDSDs) showed least
      number of peaks having low intensity and maximum displaced angles. DSC
      thermograms of drug-carrier ratios at 1:1-1:4 showed lower melting temperature
      than artemisinin and nicotinamide in all preparations. Endothermic temperature of
      artemisinin in PMs and SLVPs increased with rise of nicotinamide content upto 1:6
      ratio followed by decline. All samples showed crystallization temperature below
      the artemisinin except drug-carrier ratio 1:6 of PMs while deltaH value was
      minimum at this ratio. FDSDs produced lowest endothermic temperature than
      corresponding PMs and SLVPs. SLVPs exhibited band shifting in both functional and
      fingerprint region compared to respective PMs as exhibited by their FTIR spectra.
      FDSDs and SLVPs showed different nature of bonding among artemisinin and
      nicotinamide. FDSDs produced strongest CONH(2) bonding followed by SLVPs and PMs
      respectively. PMs produced significantly higher aqueous solubility and rate of
      dissolution as compared to artemisinin alone. SLVPs exhibited improved solubility
      and dissolution profile corresponding to PMs. FDSDs showed highest release rate
      and aqueous solubility followed by SLVPs and PMs at all ratios. PMs and SLVPs
      showed their highest dissolution profile at 1:6 drug-carrier ratio followed by
      gradual decrease while FDSDs progressed in dissolution rate with increase of
      nicotinamide content successively upto maximum at 1:10 ratio.

PMID- 22459477
TI  - Phytochemical screening, and assessment of ameliorating effect of aqueous and
      ethanolic extracts of Gmelina arborea on drug induced hepatic and renal
      insufficiency in rats.
AB  - Phytochemical screening of stem bark and leaves of Gmelina arborea; and effect of
      aqueous and ethanolic extracts of Gmelina arborea stembark on hepatic and renal
      insufficiency in rats was assessed in this study. Phytochemical screening was
      carried out on the air-dried leaf, oven-dried leaf, air-dried stembark and oven
      dried stembark samples. Sixty five (65) wister albino rats, (50.7-117.5 g) were
      divided into thirteen groups of five animals each. Three groups serve as Controls
      and were administered Cisplatin (5mg/kg b.w; i.p), Paracetamol (200mg/kg b.w;
      i.p) and Normal saline (0.002 ml/kg b.w; oral). Other groups were administered,
      either, cisplatin and extracts (1g/kg b.w; oral); Paracetamol and extracts (1g/kg
      b.w; oral); extracts alone; or drugs and combination of extracts. Animals were
      starved, 24 hours prior to sacrifice and sacrificed on the 9th day after
      commencement of treatment. Phytochemical screening results show the presence of
      alkaloid, flavonoid, tannin, saponin, cyanogenic glycoside, phytate, and
      carbohydrate. Saponin and carbohydrate were shown to be much higher in
      concentration than other phytochemicals. The percentage composition of cyanogenic
      glycoside and phytate were highest in air-dried stembark and oven-dried leaf
      samples, respectively. All the Gmelina arborea extracts and extract mixture
      administered to both paracetamol and cisplatin treated animals, significantly,
      lowers both the activities of the SGOT and SGPT, and the levels of serum
      creatinine and urea. When administered alone, the aqueous and ethanolic extracts
      show little or no sign of toxicity. Thus Gmelina arborea extracts may have
      ameliorating effect on hepatic and renal insufficiency caused by paracetamol and
      cisplatin respectively, and any inherent toxicity may be reduced or eliminated
      through adequate heat treatment.

PMID- 22459478
TI  - Antimicrobial activities of rhizomes of Polygonatum verticillatum: attributed to
      its total flavonoidal and phenolic contents.
AB  - The current study was undertaken to evaluate the rhizomes of Polygonatum
      verticillatum against various pathogenic bacteria and fungi. Broad spectrum
      antibacterial activity was demonstrated by the crude extract of the plant and its
      subsequent solvent fractions; predominantly against Gram-negative bacteria. MICs
      of the extracts against Escherchia coli, Salmonella typhi and Shigella flexeneri
      were in the range of 1.5-40 MUg/ml, 03-06 MUg/ml and 03-40 MUg/ml, respectively.
      The only sensitive Gram-positive bacterium was Staphylococcus aureus with MICs in
      the range of 75-80 MUg/ml. The fungicidal activity was limited to Microspoum
      canis and Fusarium solani and the MICs were in the range of 350-360 MUg/ml and
      190-290 MUg/ml respectively. The various fractions of rhizomes contained
      significant concentration of total flavonoidal and total phenolic contents that
      could be responsible for the current findings.

PMID- 22459479
TI  - Pharmacogenomic approaches in the treatment of breast cancer by tamoxifen.
AB  - Breast cancer (BC) is a highly diverse complaint rather than sole disease
      consisting of several markers linked to typical features of tissues, medical
      assessment and reaction to treatment. Mutation in RAS/MEK/ERK and PI3K-AKT-mTOR
      pathway is involved in pathogenesis of BC. Application of pharmacogenomics will
      lead to individualization of therapy, which is totally contrast to nowadays
      clinical practice, in which drug's effects are studied on large group of patient
      regardless of their genetic based difference. The genetic differences in persons
      affect the therapeutic action and concentration of Tamoxifen in each individual.
      Therefore, it is, concluded to choose best drug regimen for each patient on
      individual basis and to circumvent the patient by toxic effect of drug.

PMID- 22459480
TI  - Nanoparticles toxicity and their routes of exposures.
AB  - The new scientific innovation of engineering nanoparticles (NPs) at the atomic
      scale of 100 nm or less, has led to numerous novel and useful wide applications
      in electronics, chemicals, environmental protection, biological medicine.
      Manufacturers and consumers of the nanoparticles-related industrial products
      however, are likely to be exposed to these engineered nanomaterials which have
      various physical and chemical properties. These nanosize particles are likely to
      increase an unnecessary infinite toxicological effect on animals and environment,
      although their toxicological effects associated with human exposure are still
      unknown. In order to understand the effects of these exposures, this review seeks
      to examine the various toxicological portal routes associated with NPs exposures.
      These NPs can enter the host systems via skin spores, debilitated tissues,
      injection, olfactory, respiratory and intestinal tracts. These uptake routes of
      NPs may be intentional or unintentional. Their entry may lead to various
      diversified adverse biological effects. Until a clearer picture emerges, the
      limited data available suggest that caution must be exercised when potential
      exposures to NPs are encountered. Methods used in determining NPs portal of entry
      into experimental animals include pharyngeal instillation, injection, inhalation,
      cell culture lines and gavage exposures. This review also provides a step by step
      systematic approach for the easy identification and addressing of occupational
      health hazards arising from NPs.

PMID- 22459481
TI  - Enhanced vascular permeability is hypothesized to promote inflammation-induced
      carcinogenesis and tumor development via extravasation of large molecular
      proteins into the tissue.
AB  - We propose that the growth of solid tumors is dependent, in part, on the entry of
      large molecular blood-borne growth regulators into the tissue and is facilitated
      by the highly permeable nature of tumor blood vessels. There is abundant evidence
      that the tumor vasculature is hyperpermeable and tumor growth is dependent on
      mediators that increase vascular permeability (e.g., VEGF and mast cells).
      Therefore, the extravasation of plasma proteins into the interstitial space could
      be an important determinant of tumor growth. Angiogenesis promotes cancer by
      creating a network of blood vessels that supplies oxygen and nutriment. A highly
      permeable vasculature could complement this by facilitating the entry of plasma
      proteins into the tumor space, permitting them to exert effects on growth and
      survival pathways. Plasma proteins could act directly (on the cancer cells) or
      indirectly (via the stroma), and could conceivably stimulate cell proliferation,
      enhance cell survival, promote angiogenesis, and/or provide the cells with
      essential nutrients. Since increased vascular permeability is a hallmark of
      inflammation and since chronic inflammation is a forerunner to cancer, we also
      suggest that the prolonged influx of plasma proteins during chronic inflammation
      could contribute to the carcinogenic process. Perhaps over time and in sufficient
      quantity, the extruded plasma proteins and the attendant edema set up a feed
      forward cycle that exacerbates the inflammation and potentiates the formation of
      mutagens and growth regulators. It is tempting to speculate that differences in
      tumor growth/metastasis and patient outcome are at least partly due to the degree
      of permeability of the tumor vasculature.

PMID- 22459482
TI  - High-mobility group box 1 contributes to mechanical allodynia and spinal
      astrocytic activation in a mouse model of type 2 diabetes.
AB  - Chronic pain is one of the most common complications of diabetes. However,
      current treatments for diabetic pain are usually unrealistic because the
      underlying mechanisms are far from being clear. Immerging studies have implicated
      immune factors as key players in the diabetic pain. High-mobility group box 1
      (HMGB1) is an important mediator of inflammatory response, but its role in
      diabetic pain is unclear. In the present study, we observed that db/db mice (a
      model of type 2 diabetes) developed persistent mechanical allodynia from
      postnatal 2 months. Western blot showed that in postnatal 2-5 months, HMGB1 was
      significantly higher than that of the heterozygous littermates (db/+) mice.
      Intrathecal injection of a HMGB1 neutralizing antibody (anti-HMGB1) inhibited
      mechanical allodynia. Immunostaining data showed that compared with db/+ and C57
      mice (postnatal 4 months), glial fibrillary acidic protein (GFAP) staining was
      significantly increased in the spinal cord of db/db mice. Anti-HMGB1 could
      effectively decrease GFAP expression. Real-time PCR showed that in postnatal 4
      months, db/db mice induced significant increases of TNF-alpha, IL-1beta, IL-6 and
      monocyte chemoattractant protein-1 (MCP-1) in the spinal dorsal horn, while anti
      HMGB1 (50 MUg) effectively inhibited the up-regulation of these inflammatory
      mediators. Our results indicate that HMGB1 is significantly up-regulated in the
      spinal cord of type 2 diabetes, and inhibiting HMGB1 may provide a novel
      treatment for diabetic pain.

PMID- 22459483
TI  - Update: Arrhythmias (V). Paroxysmal supraventricular tachycardias and
      preexcitation syndromes.
AB  - Paroxysmal supraventricular tachycardias are fast and usually regular rhythms
      that require some structure above the bifurcation of the His bundle to be
      continued. The 3 most common types are atrial tachycardias, atrioventricular
      nodal reentrant tachycardias, and tachycardias mediated by an accessory pathway.
      The last two varieties are discussed in the present manuscript. Their prognosis
      is benign regarding life expectancy but typically they are symptomatic and
      chronically recurrent, producing a certain disability. They usually occur in
      people without structural heart disease. Pharmacologic therapy is possible, but
      given the high efficacy of catheter ablation, these procedures are frequently
      chosen. Ventricular preexcitation is due to the presence of an accessory pathway,
      usually atrioventricular. The clinical course can be asymptomatic, generating a
      characteristic electrocardiographic pattern, produce paroxysmal supraventricular
      tachycardias, or facilitate other types of arrhythmias. Very rarely, they can
      cause sudden cardiac death. The treatment of choice for symptomatic patients is
      catheter ablation of the accessory pathway. The therapeutic attitude towards
      asymptomatic preexcitation remains controversial.

PMID- 22459485
TI  - Statement on ayahuasca.

PMID- 22459486
TI  - Prevalence of antibodies to Mycoplasma synoviae in laying hens and possible
      effects on egg shell quality.
AB  - Mycoplasma synoviae (M. synoviae) can cause respiratory disease, synovitis, or
      result in a silent infection in chickens and turkeys. The importance of M.
      synoviae is well established in broilers but only a few studies have been
      conducted in layers. In the present study, the prevalence of M. synoviae in
      commercial layer flocks was estimated using ELISA. For this study, 19 commercial
      layer flocks were selected randomly from New South Wales and Queensland region of
      Australia from producers who were willing to participate in the survey. Sixty
      eggs per flocks were randomly collected, out of these 30 eggs were used for ELISA
      and remaining 30 eggs were used to estimate various egg shell quality parameters.
      Subsequently, association between the serological status of eggs for M. synoviae
      and egg shell quality was studied. In the flocks under study, seroprevalence of
      M. synoviae was found to be high at 69% (95% confidence interval (CI)=41.3-89.0).
      Statistical analysis showed an association between serological status for M.
      synoviae and egg quality parameters such as translucency, shell breaking
      strength, % shell reflectivity and shell deformation. On the other hand, there
      was no significant association between serological status for M. synoviae and
      other egg quality parameters such egg weight, egg shell weight, % egg shell or
      shell thickness.

PMID- 22459487
TI  - Agreement between the caudal fold test and serological tests for the detection of
      Mycobacterium bovis infection in bison.
AB  - The objective of this study was to estimate agreement between the caudal fold
      test (CFT) and different serological tests for the detection of Mycobacterium
      bovis infection in bison by using prevalence-adjusted bias-adjusted kappa
      (PABAK). A total of 212 of wild wood bison from Wood Buffalo National Park were
      tested with the CFT as well as several serological tests: fluorescent
      polarization assay (FPA), multiantigen print immunoassay (MAPIA), rapid lateral
      flow test (RT) and dual path platform test (DPP). For RT, 3 variations were
      conducted using 30MUl of serum (RT 30), 20MUl of serum (RT 20) and 20MUl of serum
      considering only a strong reaction as positive (RT 20 ST). The McNemar's chi(2)
      test was conducted to assess whether the proportion of positive test results to 2
      different tests differed. Two measures of agreement between pair of tests were
      estimated: the Cohen's kappa statistic and PABAK. The apparent prevalence of
      tuberculosis in the sampled animals varied depending on the diagnostic test from
      6.1% (FPA and DPP) to 47.2% (CFT). The prevalence estimated by CFT differed from
      the prevalence estimated by the other tests, whereas the prevalence estimated by
      FPA, MAPIA, RT 20 ST and DPP were not significantly different. The kappa and
      PABAK estimates calculated between CFT and the rest of the tests suggested poor
      to slight agreement between tests (k and PABAK<0.25 in all cases). The PABAK
      estimates for the pairwise combinations among serological tests were numerically
      greater than the kappa estimates (and significantly greater when FPA was compared
      to the rest of serological tests), and suggested substantial to almost perfect
      agreement (PABAK>0.75 in all cases). The disagreement between the skin and
      serological tests for the detection of M. bovis infection could be partly because
      the tests measure different immunological responses (cell-mediated vs. humoral)
      that are predominant at different stages of the infection, and partly due to
      inaccuracy of the tests. Further research is needed to evaluate the accuracy of
      diagnostic tests in order to establish a reliable case definition, combining
      different tests, to be used in the surveillance and control of tuberculosis in
      free-ranging bison populations.

PMID- 22459488
TI  - Antimicrobial use in Belgian broiler production.
AB  - The use of antimicrobials in production animals has become a worldwide concern in
      the face of rising resistance levels in commensal, pathogenic and zoonotic
      bacteria. In the years 2007 and 2008 antimicrobial consumption records were
      collected during two non consecutive production cycles in 32 randomly selected
      Belgian broiler farms. Antimicrobials were used in 48 of the 64 monitored
      production cycles, 7 farms did not use any antimicrobials in both production
      cycles, 2 farms only administered antimicrobials in one of the two production
      cycles, the other 23 farms applied antimicrobial treatment in both production
      cycles. For the quantification of antimicrobial drug use, the treatment
      incidences (TI) based on the defined daily doses (the dose as it should be
      applied: DDD) and used daily doses (the actual dose applied: UDD) were
      calculated. A mean antimicrobial treatment incidence per 1000 animals of 131.8
      (standard deviation 126.8) animals treated daily with one DDD and 121.4 (SD
      106.7) animals treated daily with one UDD was found. The most frequently used
      compounds were amoxicillin, tylosin and trimethoprim-sulphonamide with a mean
      TI(UDD) of 37.9, 34.8, and 21.7, respectively. The ratio of the UDD/DDD gives an
      estimate on correctness of dosing. Tylosin was underdosed in most of the
      administrations whereas amoxicillin and trimethoprim-sulphonamide were slightly
      overdosed in the average flock.

PMID- 22459489
TI  - Effects of the built environment on childhood obesity: the case of urban
      recreational trails and crime.
AB  - We study the effects of urban environment on childhood obesity by concentrating
      on the effects of walking trails and crime close to children's homes on their BMI
      and obesity status. We use a unique dataset, which combines information on
      recreational trails in Indianapolis with data on violent crimes and
      anthropomorphic and diagnostic data from children's clinic visits between 1996
      and 2005. We find that having a trail near a home reduces children's weight.
      However, the effect depends on the amount of nearby violent crimes. Significant
      reductions occur only in low crime areas and trails could have opposite effects
      on weight in high crime areas. These effects are primarily among boys, older
      children, and children who live in higher income neighborhoods. Evaluated at the
      mean length of trails this effect for older children in no crime areas would be a
      reduction of 2 lb of the body weight. Falsification tests using planned trails
      instead of existing trails, show that trails are more likely to be located in
      areas with heavier children, suggesting that our results on effects of trails
      represent a lower bound.

PMID- 22459490
TI  - Two discreet subsets of CD8 T cells modulate PLP(91-110) induced experimental
      autoimmune encephalomyelitis in HLA-DR3 transgenic mice.
AB  - Previously we showed that transgenic mice expressing human HLA-DR3 gene are
      susceptible to PLP(91-110) induced experimental autoimmune encephalomyelitis
      (EAE) and can serve as an animal model of multiple sclerosis (MS). HLA-DR3 mice
      with EAE showed increased number of CD8 T cells indicating their important role
      in disease pathogenesis. The role of CD8 T cells in MS, an inflammatory
      demyelinating disease of CNS, has been enigmatic as it has been assigned both
      regulatory and pathogenic roles. Therefore, to evaluate the role of CD8 T cells,
      we generated CD8 deficient HLA-DR3 transgenic mice (DR3.CD8(-/-)). Immunization
      with PLP(91-110) led to more severe EAE in DR3.CD8(-/-) mice compared to HLA-DR3
      mice indicating a regulatory role for CD8 T cells. Interestingly, DR3.CD8(-/-)
      mice with EAE showed decreased CNS pathology compared to DR3 mice thus suggesting
      a pathogenic role for CD8 T cells. We show that these two subsets of CD8 T cells
      can be differentiated based on the surface expression of CD122 (IL-2 Rbeta
      chain). CD8 T cells expressing CD122 (CD8+CD122+) play a regulatory role while
      CD8+CD122- T cells act as a pathogenic subset. CD122 expressing CD8 T cells are
      the regulatory subset of CD8 T cells and regulate the encephalitogenic CD4 T
      cells through direct modulation of antigen presenting cells and/or through the
      release of immunoregulatory cytokines such as IL-10, IFNgamma and TGFbeta. We
      also showed that adoptive transfer of CD8CD122- T cells caused increased spinal
      cord demyelination indicating that these are pathogenic subset of CD8 T cells.
      Our study suggests that CD8+ T cells play both regulatory as well as pathogenic
      role in disease pathogenesis of EAE. A better understanding of these subsets
      could aid in designing novel therapy for MS patients.

PMID- 22459491
TI  - Mass spectrometric detection of antigen-specific immunoglobulin peptides in
      paraneoplastic patient sera.
AB  - Paraneoplastic neurological syndromes (PNS) are severe immune mediated effects of
      cancer. The presence of IgG autoantibodies against onconeural antigens in serum
      is a hallmark of the disease. Multiple paraneoplastic antibodies have been
      described, including antibodies against HuD, Yo, amphiphysin and CV2. In this
      study, we test the hypothesis that primary amino-acid structures of the antigen
      binding part of antibodies from various individuals share common sequences that
      are specific for each auto-antigen. We selected 60 patients with PNS, associated
      with antibodies against HuD, Yo, Amp or CV2. Affinity purified IgG was separated
      using SDS-PAGE and IgG heavy chains were excised, trypsinized and subjected to
      tandem mass spectrometry. We selected masses that uniquely identified a PNS
      autoantibody group, and used MS/MS fragmentation spectra to obtain information on
      peptide sequences. Out of 19,173 unique masses, 28 immunoglobulin-derived
      peptides were found exclusively in samples from a single autoantibody defined PNS
      group. Our results confirm that specific peptide structures exist in the antigen
      binding site of IgG that are shared between individuals harboring autoantibodies
      against the same onconeural antigen. Thus, the immune response in these patients
      followed converging paths during the rearrangement, selection and maturation of
      immunoglobulin sequences. The identified peptides can be applied in the diagnosis
      of PNS, but these data also indicate that a similar approach in a variety of
      other diseases involving an immune response would have an appealing outlook.

PMID- 22459492
TI  - Adenomyosis and infertility.

PMID- 22459493
TI  - Adults with congenital or acquired facial disfigurement: impact of appearance on
      social functioning.
AB  - This study evaluates the impact of congenital and acquired facial disfigurement
      on social functioning in adults and whether this differs from adults without
      facial disfigurement. Moreover, the predictive value of objective and subjective
      appearance on social functioning is explored. Fifty-nine adults with severe
      congenital facial disfigurement, 59 adults with traumatically acquired facial
      deformities in adulthood, and 120 adults without facial disfigurement, completed
      the Scale for Interpersonal Behaviour, Social Avoidance and Distress Scale, and
      Visual Analogue Scale for facial appearance satisfaction. The impact of
      congenital and acquired facial disfigurement on social functioning in adults is
      similar and significantly differed from the reference group. The level of stress
      evoked by interpersonal behaviour, and social anxiety and distress were not
      significantly different between the groups. Only the patient's subjective
      appearance was a predictor of social functioning. Avoiding stress caused by
      stigmatization and uncertainty about reactions of others, leads to less frequent
      interpersonal behaviour in adults with facial disfigurement. The fact whether the
      deformity is congenital or acquired in adulthood has no influence on social
      functioning. Patient's satisfaction with facial appearance is more important than
      the objective severity of the deformity; in this context realistic expectations
      of the patient considering additional surgery are important.

PMID- 22459494
TI  - Developing World ENT: a global responsibility.
AB  - There exists a tremendous opportunity for otolaryngologists from developed
      countries to make a substantial contribution beyond their daily clinical
      practice, through involvement in teaching and training in the developing world.
      This article sets out the challenges presented by ENT practice within the
      developing world, and discusses ways in which these challenges can be addressed.

PMID- 22459495
TI  - Inter-annual variability of wet season freshwater plume extent into the Great
      Barrier Reef lagoon based on satellite coastal ocean colour observations.
AB  - Riverine freshwater plumes are the major transport mechanism for nutrients,
      sediments and pollutants into the Great Barrier Reef (GBR) lagoon and connect the
      land with the receiving coastal and marine waters. Knowledge of the variability
      of the freshwater extent into the GBR lagoon is relevant for marine park
      management to develop strategies for improving ecosystem health and risk
      assessments. In this study, freshwater extent has been estimated for the entire
      GBR lagoon area from daily satellite observations of the Moderate Resolution
      Imaging Spectroradiometer (MODIS) between 2002 and 2010. To enable a reliable
      mapping of freshwater plumes we applied a physics-based coastal ocean colour
      algorithm, that simultaneously retrieves chlorophyll-a, non-algal particulate
      matter and coloured dissolved organic matter (CDOM), from which we used CDOM as a
      surrogate for salinity (S) for mapping the freshwater extent.

PMID- 22459496
TI  - Phenolic endocrine disrupting chemicals (EDCs) in Anzali Wetland, Iran: elevated
      concentrations of 4-nonylphenol, octhylphenol and bisphenol A.
AB  - We have studied the distribution and value of phenolic endocrine disrupting
      chemicals (EDCs) in surface sediment samples taken from Anzali Wetland, Iran.
      These samples were collected from 22 stations during the time span of June-May
      2010. In each of the sampling stations, we detected 4-nonylphenol (4-NP),
      octylphenol (OP), and bisphenol A (BPA) with maximal concentrations of 29, 4.3,
      and 7 MUg g(-1) dry weight (dw), respectively. High levels of alkylphenols (APs)
      and BPA were also found near urban areas. Furthermore there were no significant
      differences between those stations in terms of the detected levels. One of the
      important factors in controlling the fate of these compounds in the aquatic
      environment appeared to be Total Organic Carbon (TOC). Hierarchical cluster
      analysis showed differences in the biomarker characteristics of EDCs and TOC
      between the stations. Our findings indicate that EDCs are ubiquitous in sediments
      from northeast Wetlands of Iran, contaminating the aquatic habitats in this area.

PMID- 22459497
TI  - The microbiological condition of minced pork prepared at retail stores in Athens,
      Greece.
AB  - Minced pork samples (n = 150) obtained from butchers' shops and supermarkets in
      Greece, during summer (n = 75) and winter (n = 75), were subjected to
      microbiological analysis. Microbial counts (log CFU/g) for the parameters tested
      were: total viable count (TVC), 6.8 +/- 1.0; Pseudomonas spp., 6.4 +/- 1.2;
      Brochothrix thermosphacta, 5.9 +/- 1.1; lactic acid bacteria, 5.3 +/- 1.0; yeasts
      and moulds, 4.6 +/- 0.7; hydrogen sulfide (H(2)S)-producing bacteria, 4.3 +/-
      1.3; Enterobacteriaceae, 3.6 +/- 1.2; total coliforms, 2.9 +/- 1.1; Escherichia
      coli, 1.4 +/- 0.7; Staphylococcus spp., 4.3 +/- 1.0; S. aureus, 2.4 +/- 0.9, and
      Listeria spp., 1.4 +/- 0.6. The highest correlations were between TVC and
      pseudomonads, B. thermosphacta and H(2)S-producing bacteria, while the lowest
      were between total coliforms and all other groups of microorganisms except
      Enterobacteriaceae. The type of retail outlet and the seasonality of sampling did
      not have any significant effects (p>0.05) on minced pork meat quality.
      Interrelationships between (i) meat quality and shelf life, (ii) hygienic
      conditions during mince preparation and (iii) personnel hygiene were revealed.

PMID- 22459498
TI  - Dietary influence on the m. longissimus dorsi fatty acid composition of lambs in
      relation to protein source.
AB  - Dietary lipid effect, as a consequence of protein supplement, on lamb m.
      longissimus dorsi fatty acid composition was investigated, with emphasis on
      biohydrogenation intermediates. Crossbred lambs (White Swedish Landrace * Texel)
      were fed a barley-based diet without (CON) or with protein supplements including
      peas (PEA), rapeseed cake (RC) or hempseed cake (HC). The HC diet resulted in the
      highest muscle 22:6n-3 proportion, with the RC diet being similar (P<0.05).
      Protein supplement did not affect the c9,t11 conjugated linoleic acid (CLA)
      proportion, however the HC diet increased some minor CLA isomers, including
      t10,c12 CLA (P<0.05). The t10-18:1 and total trans-18:1 were lowest for the RC
      diet (P<0.05), likely relating to rumen conditions and precursor availability.
      The saturated, monounsaturated and branched-chain fatty acids were largely
      unaffected by protein supplement. In conclusion, feeding the RC diet lowered the
      t10-18:1 and total trans-18:1 in meat, and modestly increased 22:6n-3 content.
      The direction of these changes would be beneficial, making the RC diet the
      preferred protein supplement; however the magnitude of the changes in the present
      experiment may not be sufficient to have an impact on human health.

PMID- 22459499
TI  - A systematic review of the effect of institution and surgeon factors on surgical
      outcomes for gastric cancer.

PMID- 22459500
TI  - The utility of health and wealth.
AB  - Tradeoffs between health and wealth are among the most important decisions
      individuals make, and are central to social and economic policy. Yet, only a few
      studies have investigated the utility of health and wealth empirically. This
      paper investigates this utility function both theoretically and empirically. We
      conduct detailed personal interviews with 180 cancer patients, and also obtain
      questionnaires from 132 diabetes patients. We find strong support for the utility
      function U(h, w)=h.log(w), where h denotes health and w denotes wealth.

PMID- 22459501
TI  - The effect of comprehensive state tobacco control programs on adult cigarette
      smoking.
AB  - This study is the second to use national survey data to assess the effect of
      comprehensive state tobacco control programs on adult cigarette smoking. Data are
      drawn from the Behavioral Risk Factor Surveillance System (1991-2006) and reveal
      consistent evidence that these programs have a statistically significant effect
      to reduce prevalence of cigarette smoking among adults. Simulations indicate that
      had all states spent the CDC recommended level of funding from 1991 to 2006 then
      cigarette smoking prevalence would have been 1.40-8.07% lower in 2006,
      translating to between 635,000 and 3.7 million fewer adult cigarette smokers.

PMID- 22459502
TI  - A new approach to detect congestive heart failure using sequential spectrum of
      electrocardiogram signals.
AB  - The aim of this study is to evaluate the discriminative power of sequential
      spectrum analysis of the short-term electrocardiogram (ECG) time series in
      separating normal and congestive heart failure (CHF) subjects. The raw ECG time
      series is transformed into a series of discretized binary symbols and the
      distribution of mono-sequences (i.e., tuples containing only one type of symbol
      '0' or '1') is computed. The relative distribution of mono-sequences containing
      only one type of symbol constitutes binary occupancy for that symbol in the
      sequential spectrum. The quantified approximate entropies of the binary
      occupancies in the sequential spectra are found to have potential in
      discriminating normal and CHF subjects and thus can significantly add to the
      prognostic value of traditional cardiac analysis. The statistical analyses and
      the receiver operating characteristic curve (ROC) analysis confirm the robustness
      of this new approach, which exhibits an average accuracy, average sensitivity,
      average positive predictivity, and average specificity, all 100.0%.

PMID- 22459503
TI  - Liquid chromatography-tandem mass spectrometric assay for the light sensitive
      calcium channel antagonist lacidipine in human plasma.
AB  - A novel, rapid and sensitive liquid chromatography/tandem mass spectrometry
      method was developed and validated for the quantification of calcium channel
      antagonist lacidipine in human plasma. Carbamazepine was used as an internal
      standard. Analyte and the internal standard were extracted from human plasma by
      solid-phase extraction technique. The reconstituted samples were chromatographed
      on a C(18) column by using a mixture of acetonitrile-ammonium acetate buffer (5
      mM) (80:20, v/v) as the mobile phase at a flow rate of 1.0 mL/min. The
      calibration curve obtained was linear (r(2)>=0.9990) over the concentration range
      of 0.05-12.5 ng/mL. The multiple reaction-monitoring mode was used for
      quantification of ion transitions at m/z 456.2/354.2 and 237.1/194.1 for the drug
      and the internal standard, respectively. The results of the intra- and inter-day
      precision and accuracy studies were well within the acceptable limits. A run time
      of 2.2 min for each sample made it possible to analyze more than 300 plasma
      samples per day. The proposed method was found to be applicable to clinical
      studies.

PMID- 22459504
TI  - The development and application of a system for simultaneously determining anti
      infectives and nasal decongestants using on-line solid-phase extraction and
      liquid chromatography-tandem mass spectrometry.
AB  - A method for the simultaneous analysis of antibiotics, antiviral and nasal
      decongestants in treated sewage effluent and surface water has been developed and
      validated. The method uses on-line solid phase extraction (SPE) of injected high
      volume samples in conjunction with liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). This method includes a range of antibiotics (Trimethoprim,
      Oxytetracycline, Ofloxacin, Norfloxacin, Ciprofloxacin, Azithromycin,
      Doxycycline, Sulfamethoxazole, Erythromycin and Clarithromycin), an antiviral
      (Oseltamivir) and nasal decongestants (Naphazoline, Oxymetazoline and
      Xylometazoline). The method's detection limits (MDLs) ranged from (0.2 ng L(-1))
      to (3.1 ng L(-1)), based on a 1 mL extraction volume. Its intra-day precision was
      determined by performing nine runs with 200 ng L(-1) samples; the intra-day
      relative standard deviation (RSD) ranged from 1% to 19%. Inter-day precision was
      determined by analyzing samples in triplicate over the course of three days,
      yielding relative standard deviations ranging from <5% to <26%. The linearity
      (R(2)) for all compounds tested was >0.90. Spike relative recoveries ranged from
      40% to 157% and 40% to 152% for STP effluent and surface water samples,
      respectively. Finally, the method was used to analyze real effluent and surface
      water.

PMID- 22459505
TI  - A high pH based reversed-phase high performance liquid chromatographic method for
      the analysis of aminoglycoside plazomicin and its impurities.
AB  - A reversed-phase high performance liquid chromatographic (RP-HPLC) method has
      been developed for the aminoglycoside (AG) plazomicin (ACHN-490). This method
      employed a high pH mobile phase (pH>11) with a gradient of 0.25 M ammonium
      hydroxide in water and acetonitrile, an XBridge C(18) column and UV detection at
      210 nm. Although the molar UV absorption of plazomicin is weak, the high pH
      conditions of this method allow for higher loadings, which compensates for the
      inherent low UV sensitivity. Under these high pH conditions, impurities and
      degradants were base line separated from plazomicin. The mobile phases used for
      this method allowed for on-line mass detection for the impurities and degradants.
      The RP-HPLC method has been validated in terms of specificity, linearity and
      range, accuracy, and precision. The analytical method met specificity
      requirements of a homogenous peak with no interferences from the blank or from
      the known impurities in plazomicin. The linearity of the method for the
      plazomicin impurity determination was excellent, with a coefficient of
      determination (r(2)) of 0.9993, over the freebase (FB) concentration range of
      0.0025-3.0 mg/mL. The method is capable of detecting impurities down to 0.1% of
      the peak area of plazomicin. A single point standard at a concentration of 1.0
      mg/mL FB was validated over the range of 50-150% for quantitation of the freebase
      content (the assay) in bulk drug substance. The mean recoveries of FB are in the
      range 98.6-102.0% with a mean RSD (relative standard deviation) <1.0%. The study
      also examined the method precision for purity, impurities and the assay with two
      instruments on two different days. The method showed adequate accuracy and
      precision for the intended use. This high pH method was successfully used to
      determine the impurity and measure the drug content in the final plazomicin drug
      substance. In addition, the method with an on-line mass spectrometry detector has
      been used to characterize the structures of the impurities in plazomicin.

PMID- 22459506
TI  - Exposure, probable PTSD and lower respiratory illness among World Trade Center
      rescue, recovery and clean-up workers.
AB  - BACKGROUND: Thousands of rescue and recovery workers descended on the World Trade
      Center (WTC) in the wake of the terrorist attack of September 11, 2001 (9/11).
      Recent studies show that respiratory illness and post-traumatic stress disorder
      (PTSD) are the hallmark health problems, but relationships between them are
      poorly understood. The current study examined this link and evaluated
      contributions of WTC exposures. METHOD: Participants were 8508 police and 12 333
      non-traditional responders examined at the WTC Medical Monitoring and Treatment
      Program (WTC-MMTP), a clinic network in the New York area established by the
      National Institute for Occupational Safety and Health (NIOSH). We used structural
      equation modeling (SEM) to explore patterns of association among exposures, other
      risk factors, probable WTC-related PTSD [based on the PTSD Checklist (PCL)],
      physician-assessed respiratory symptoms arising after 9/11 and present at
      examination, and abnormal pulmonary functioning defined by low forced vital
      capacity (FVC). RESULTS: Fewer police than non-traditional responders had
      probable PTSD (5.9% v. 23.0%) and respiratory symptoms (22.5% v. 28.4%), whereas
      pulmonary function was similar. PTSD and respiratory symptoms were moderately
      correlated (r=0.28 for police and 0.27 for non-traditional responders). Exposure
      was more strongly associated with respiratory symptoms than with PTSD or lung
      function. The SEM model that best fit the data in both groups suggested that PTSD
      statistically mediated the association of exposure with respiratory symptoms.
      CONCLUSIONS: Although longitudinal data are needed to confirm the mediation
      hypothesis, the link between PTSD and respiratory symptoms is noteworthy and
      calls for further investigation. The findings also support the value of
      integrated medical and psychiatric treatment for disaster responders.

PMID- 22459507
TI  - Coping strategies and adaptation to coronary artery bypass surgery as experienced
      by three couples.
AB  - OBJECTIVE: Coping strategies affect the psychosocial adaptation of couples in
      which one of the partners has undergone coronary artery bypass grafting. Research
      has focused on coping strategies of patients and spouses as individuals, but
      little is known about how couples cope with this procedure. The purpose of this
      study was to understand couples' coping strategies and their influence on
      adaptation to bypass surgery. METHODS: Three couples were recruited from the
      Cardiac Wellness Institute of Calgary, Alberta, Canada. The descriptive
      phenomenological psychological method was used to analyze data from 2 interviews
      with each couple. RESULTS: The analysis revealed a single structure that
      described the couples' lived experiences. The structure and interview data
      revealed coping strategies and key factors influencing adaptation postsurgery.
      CONCLUSION: Coping strategies, such as redefining the illness, seeking spiritual
      support, and partnering, enhanced psychosocial adaptation for couples. In
      addition, marital quality, coping congruence, and shared meaning contributed to
      effective coping and better adaptation.

PMID- 22459508
TI  - Feasibility and compliance with daily home electrocardiogram monitoring of the QT
      interval in heart transplant recipients.
AB  - BACKGROUND: Recent evidence suggests that acute allograft rejection after heart
      transplantation causes an increased QT interval on electrocardiogram (ECG). The
      aims of this pilot study were to (1) determine whether heart transplant
      recipients could achieve compliance in transmitting a 30-second ECG every day for
      1 month using a simple ECG device and their home telephone, (2) evaluate the ease
      of device use and acceptability by transplant recipients, and (3) evaluate the
      quality of transmitted ECG tracings for QT-interval measurement. METHODS: A
      convenience sample of adult heart transplant recipients were recruited and
      trained to use the device (HeartOne, Aerotel Medical Systems, Holon, Israel).
      Lead II was used with electrodes that were easy to slip on and off (expandable
      metal wrist watch-type electrode for right wrist and C-shaped band electrode for
      left ankle). Patients used a toll-free number with automated voice prompts to
      guide their ECG transmission to the core laboratory for analysis. RESULTS: Thirty
      one subjects (72% were male; mean age of 52 +/- 17 years; 37% were nonwhite)
      achieved an ECG transmission compliance of 73.4% (daily) and 100% (weekly). When
      asked, how difficult do you think it was to record and transmit your ECG by
      phone, 90% of subjects replied "somewhat easy" or "extremely easy." Of the total
      644 ECGs that were transmitted by subjects, 569 (89%) were acceptable quality for
      QT-interval measurement. The mean QTc was 448 +/- 44 ms (440 +/- 41 ms for male
      subjects and 471 +/- 45 ms for female subjects). Eleven subjects (35%) had an
      extremity tremor, and 19 subjects (55%) had >= 1+ left leg edema. Neither of
      these conditions interfered with ECG measurements. CONCLUSION: Transplant
      recipients are compliant with recording and transmitting daily and weekly ECGs.

PMID- 22459510
TI  - Separation of plastic waste via the hydraulic separator Multidune under different
      geometric configurations.
AB  - The recovery of high-quality plastic materials is becoming an increasingly
      challenging issue for the recycling sector. Technologies for plastic recycling
      have to guarantee high-quality secondary raw material, complying with specific
      standards, for use in industrial applications. The variability in waste plastics
      does not always correspond to evident differences in physical characteristics,
      making traditional methodologies ineffective for plastic separation. The
      Multidune separator is a hydraulic channel allowing the sorting of solid
      particles on the basis of differential transport mechanisms by generating
      particular fluid dynamic conditions due to its geometric configuration and
      operational settings. In this paper, the fluid dynamic conditions were
      investigated by an image analysis technique, allowing the reconstruction of
      velocity fields generated inside the Multidune, considering two different
      geometric configurations of the device, Configuration A and Configuration B.
      Furthermore, tests on mono- and bi-material samples were completed with varying
      operational conditions under both configurations. In both series of experiments,
      the bi-material samples were composed of differing proportions (85% vs. 15%) to
      simulate real conditions in an industrial plant for the purifying of a useful
      fraction from a contaminating fraction. The separation results were evaluated in
      terms of grade and recovery of the useful fraction.

PMID- 22459509
TI  - Accumulation of furanocoumarins by Bituminaria bituminosa in relation to plant
      development and environmental stress.
AB  - Bituminaria bituminosa (L.) C.H. Stirton (Fabaceae) accumulates high
      concentrations of the furanocoumarins (FCs) angelicin and psoralen, which protect
      against infection and herbivory. The effects on FC accumulation of the exposure
      of two populations of B. bituminosa to abiotic stress (cold, heat and drought)
      under field conditions were determined, as well as the effect of temperature
      under controlled conditions, in hydroponic culture. In field conditions, psoralen
      and angelicin levels in the leaf dry matter were 400-6000 and 1500-11,000 MUg g(
      ), respectively. There were significant effects of population on the psoralen
      concentration and psoralen:angelicin ratio. In hydroponic culture, exposure to a
      diurnal temperature of 33  degrees C increased FC levels in population Calnegre
      but not in Llano del Beal, compared with plants grown at 22  degrees C; however,
      high summer temperatures in the field (>30  degrees C) did not coincide with the
      highest leaf FC levels, since the plants accumulated FCs preferentially in the
      fruits. Hence, leaf FC levels were higher in winter. Irrigation, to alleviate
      water stress in the semi-arid conditions, increased the fruit psoralen
      concentration but produced only minor decreases in leaf FC levels. There was a
      significant, positive correlation (P < 0.001) between the FC and nitrogen
      concentrations in the plant organs analysed (both increased in the order: fruits
      > growing leaves > mature leaves), reflecting their respective contributions to
      plant fitness. The genetically- and developmentally-regulated accumulation of FCs
      by B. bituminosa is altered by short-term variations in environmental conditions,
      particularly temperature.

PMID- 22459511
TI  - Pilot-scale anaerobic co-digestion of municipal biomass waste and waste activated
      sludge in China: effect of organic loading rate.
AB  - The effects of organic loading rate on the performance and stability of anaerobic
      co-digestion of municipal biomass waste (MBW) and waste activated sludge (WAS)
      were investigated on a pilot-scale reactor. The results showed that stable
      operation was achieved with organic loading rates (OLR) of 1.2-8.0 kg volatile
      solid (VS) (m(3)d)(-1), with VS reduction rates of 61.7-69.9%, and volumetric
      biogas production of 0.89-5.28 m(3) (m(3)d)(-1). A maximum methane production
      rate of 2.94 m(3) (m(3)d)(-1) was achieved at OLR of 8.0 kg VS (m(3)d)(-1) and
      hydraulic retention time of 15 days. With increasing OLRs, the anaerobic reactor
      showed a decrease in VS removal rate, average pH value and methane concentration,
      and a increase of volatile fatty acid concentration. By monitoring the biogas
      production rate (BPR), the anaerobic digestion system has a higher acidification
      risk under an OLR of 8.0 kg VS (m(3)d)(-1). This result remarks the possibility
      of relating bioreactor performance with BPR in order to better understand and
      monitor anaerobic digestion process.

PMID- 22459512
TI  - Landfill aeration worldwide: concepts, indications and findings.
AB  - The creation of sustainable landfills is a fundamental goal in waste management
      worldwide. In this connection landfill aeration contributes towards an
      accelerated, controlled and sustainable conversion of conventional anaerobic
      landfills into a biological stabilized state associated with a minimised emission
      potential. The technology has been successfully applied to landfills in Europe,
      North America and Asia, following different strategies depending on the
      geographical region, the specific legislation and the available financial
      resources. Furthermore, methodologies for the incorporation of landfill aeration
      into the carbon trade mechanisms have been developed in recent years. This
      manuscript gives an overview on existing concepts for landfill aeration; their
      application ranges and specifications. For all of the described concepts examples
      from different countries worldwide are provided, including details regarding
      their potentials and limitations. Some of the most important findings from these
      aeration projects are summarised and future research needs have been identified.
      It becomes apparent that there is a great demand for a systematisation of the
      available results and implications in order to further develop and optimise this
      very promising technology. The IWWG (International Waste Working Group) Task
      Group "Landfill Aeration" contributes towards the achievement of this goal.

PMID- 22459514
TI  - Labdane-type diterpenes and flavones from Dodonaea viscosa.
AB  - A new labdane diterpenoid, 2,18-dihydroxylabda-7,13(E)-dien-15-oic acid (1),
      together with two known labdane diterpenes (3, 4), a new flavone, 5,7-dihydroxy
      3,6,4'-trimethoxy-3'-(4-hydroxy-3-methyl-but-2-enyl)flavone (2) with three known
      flavones (5-7) were isolated from the aerial parts of Dodonaea viscosa. Their
      structures were determined by extensive analysis of spectroscopic data (1D and 2D
      NMR, MS) and by comparison with literature data. The anti-inflammatory activity
      of five compounds (1-5) was evaluated with a flow cytometry TNF-alpha secretion
      assay on human THP-1 cell line.

PMID- 22459513
TI  - Electrospun elastin-like polypeptide enriched polyurethanes and their
      interactions with vascular smooth muscle cells.
AB  - In vascular tissue, elastin is an essential extracellular matrix protein that
      plays an important biomechanical and biological signalling role. Native elastin
      is insoluble and is difficult to extract from tissues, which results in its
      relatively rare use for the fabrication of vascular tissue engineering scaffolds.
      Recombinant elastin-like polypeptide-4 (ELP4), which mimics the structure and
      function of native tropoelastin, represents a practical alternative to the native
      elastic fibre for vascular applications. In this study, electrospinning was
      utilized to fabricate fibrous scaffolds which were subsequently surface modified
      with ELP4 and used as substrates for smooth muscle cell culture. ELP4 surface
      modified materials demonstrated enhanced smooth muscle cell (SMC) adhesion and
      maintenance of cell numbers over a 1-week period relative to controls. SMCs
      seeded on the ELP4 surface modified materials were also shown to exhibit the cell
      morphology and biological markers of a contractile phenotype including a spindle
      like morphology, actin filament organization and smooth muscle myosin heavy chain
      expression. Competitive inhibition experiments demonstrated that the elastin
      laminin cell surface receptor and its affinity for the VGVAPG peptide sequence on
      ELP4 molecules are likely involved in the initial SMC contact with the ELP4
      modified materials. Elastin-like polypeptides show promise as surface modifiers
      for candidate scaffolds for engineering contractile vascular tissues.

PMID- 22459515
TI  - Perspectives on cell reprogramming with RNA.
AB  - Recent advances in cell reprogramming have permitted the development of different
      stem cell lines and specific differentiated cell types using distinct
      technologies. Cell reprogramming is largely mediated by DNA and RNA. In this
      review, we explore the RNA-mediated cell reprogramming to induce specific target
      cell generation including stem cells, brain cells and cardiac cells. The ability
      of RNA populations to produce direct cell to cell phenotypic conversion is called
      Transcriptome Induced PhenotypeRemodeling (TIPeR). The theory and utility of RNA
      use for cellular reprogramming is explored in this review.

PMID- 22459516
TI  - Basic concepts in skin biopsy. Part I.
AB  - The aim of these reviews is to describe the reasons for performing skin biopsy,
      to provide indications for the choice of area to be biopsied and the preparation
      of the sample, and to summarize the various complications of dermatologic
      surgery. In addition, we present a guide for selecting the biopsy technique based
      on the suspected diagnosis and on the area to be biopsied. Finally, the various
      artifacts that can complicate interpretation of results are described, together
      with the methods used to prevent their appearance insofar as is possible. The aim
      of this guide is to improve the diagnostic yield of biopsies and to highlight the
      importance of a correct clinical-histological correlation.

PMID- 22459517
TI  - Anatomy of a drug shortage.

PMID- 22459518
TI  - Article served as inspiration for continued journaling.

PMID- 22459519
TI  - Oral care for hospice patients with severe trismus.
AB  - Oral care is a hallmark of attentive, high-quality nursing care. Oral care
      improves a patient's sense of well-being, communication, and nutritional status,
      and lowers the risk for pneumonia. However, for patients with severe trismus,
      oral care may seem impossible. Trismus is the inability to open the mouth more
      than 35 mm and often results from medical therapies for head and neck cancers.
      This article details a simple approach to oral care that was implemented
      successfully with five hospice patients with severe trismus.

PMID- 22459520
TI  - Effect of massage therapy for postsurgical mastectomy recipients.
AB  - This quality improvement pilot study evaluated the effect of massage therapy on
      pain, anxiety, and overall well-being in women who received mastectomies at a
      busy hospital practice. Participants reported a significant reduction in pain,
      stress, and muscle tension, as well as an increase in relaxation. Oncology nurses
      should consider the feasibility of massage therapy as a valuable nonpharmcologic
      pain management strategy.

PMID- 22459521
TI  - Torsade de pointes, prolonged QT intervals, and patients with cancer.
AB  - Many kinase inhibitors, chemotherapeutic agents, antiemetics, antibiotics, and
      antifungal agents can prolong QT intervals, placing the patient as risk for the
      life-threatening ventricular arrhythmia Torsade de pointes (Tdp). In addition,
      common electrolyte imbalances experienced by many patients with cancer compound
      the risk. Because numerous medications used in oncology and common electrolyte
      imbalances in patients with cancer increase the risk for Tdp, oncology nurses
      must be informed about this life-threatening arrhythmia.

PMID- 22459522
TI  - Pilates for breast cancer survivors.
AB  - Pilates has been advocated for rehabilitation of breast cancer survivors despite
      little scientific evidence. The authors of this article have examined the
      feasibility of a Pilates program in postmastectomy breast cancer survivors and
      the impact on physical and psychological parameters. Fifteen breast cancer
      survivors were recruited in a one-arm study of 12 weeks of Pilates exercises. The
      authors assessed recruitment, adherence, and attrition, and measured changes in
      shoulder and neck range of motion, posture, height, arm volume, quality of life,
      mood, and body image from pre- to postintervention. Of 26 eligible patients, 15
      enrolled, 13 completed the study, and 10 performed more than 50% of the
      recommended sessions. Statistically significant improvements emerged for shoulder
      abduction and internal rotation on the affected side, neck rotation toward the
      unaffected side, and neck flexion. The affected side arm volume and the interlimb
      volume discrepancy increased. Significant improvements were reported in quality
      of life, mood, and body image. The improvements in physical and psychological
      outcomes are promising and deserve further evaluation in a randomized, controlled
      study. The increase in affected arm volume also warrants additional
      investigation.

PMID- 22459523
TI  - Loneliness, depression, and social support of patients with cancer and their
      caregivers.
AB  - Loneliness is a significant psychosocial concern for patients with cancer, and
      depression may be an antecedent to loneliness. To date, no studies have directly
      addressed the relationship of loneliness, depression, and social support among
      Turkish patients with cancer and their caregivers. The emotional responses that
      result from a cancer diagnosis vary and may include anxiety, anger, frustration,
      or depression. Because of the unexpected demands and emotions thrust on them, the
      caregivers of patients with cancer may be just as likely to experience loneliness
      or depression following a cancer diagnosis. As a result, this study sought to
      examine that relationship among a sample of 60 patients with cancer and 60
      caregivers.

PMID- 22459524
TI  - Cancer and facial disfigurement: reducing survivors' stigma in social
      interaction.
AB  - Patients with orbital and periorbital cancer expect to be cured or survive for
      several years after their malignancy is detected and surgically removed. However,
      despite advancements in reconstructive surgery, survivors often remain facially
      disfigured and spend significant portions of their lives dealing with stigma, a
      mark of social disgrace. Although research remains limited, this article
      describes a qualitative study of social interaction leading to stigma in
      individuals with facial disfigurement caused by cancer surgery, as well as the
      experiences of their family members. In particular, the current study focused on
      interaction between patients and strangers and acquaintances (secondary groups).
      In-depth interviews with patients and their family members were conducted and
      analyzed using Grounded Theory. Three primary patterns of interaction were
      identified: intrusion, sympathy, and benign neglect. Those patterns refer to
      conditions that are decreasingly favorable to the creation of stigma, where
      intrusion and sympathy foster stigma but benign neglect does not. Through that
      knowledge, oncology nurses will be able to better inform patients and family
      members on the conditions leading to stigma.

PMID- 22459525
TI  - The impact of chemotherapy-induced cognitive impairment on the psychosocial
      adjustment of patients with nonmetastatic colorectal cancer.
AB  - Colorectal cancer is the third most commonly diagnosed cancer in Canada.
      Chemotherapy often is used as treatment for colorectal cancer, and studies have
      documented cognitive changes in patients after chemotherapy treatment. What
      remains unclear is the impact of such changes on a person's roles and
      relationships, herein referred to as psychosocial adjustment. The purpose of this
      research was to explore group differences in psychosocial adjustment and
      chemotherapy-induced cognitive impairment in patients with colorectal cancer.
      Participants were assessed cross-sectionally, at various time points along their
      treatment trajectory, using the Psychosocial Adjustment to Illness Scale-Self
      Report (PAIS-SR) and the Cambridge Neuropsychological Test Automated Battery
      (CANTAB). A statistically nonsignificant negative association was indicated
      between PAIS-SR and CANTAB results, indicating that they would have no meaning in
      a clinical context. No differences between groups were observed in terms of
      cognitive ability; however, patients who completed chemotherapy appeared to be at
      a higher risk for psychosocial maladjustment. This study suggests that cognitive
      changes do not influence patients' relationships and functional roles, as
      indicated from the PAIS-SR.

PMID- 22459526
TI  - Understanding taste dysfunction in patients with cancer.
AB  - Taste dysfunction is a significant but underestimated issue for patients with
      cancer. Impaired taste results in changes in diet and appetite, early satiety,
      and impaired social interactions. Nurses can play a key role in educating
      patients and families on the pathophysiology of taste dysfunction by suggesting
      interventions to treat the consequences of taste dysfunction, when available, and
      offering psychosocial support as patients cope with this often devastating
      consequence of treatment. Taste recognition helps humans identify the nutritional
      quality of food and signals the digestive tract to begin secreting enzymes.
      Spoiled or tainted foods typically are recognized by their bad taste. Along with
      the other sensory systems, taste is crucial for helping patients treated for
      cancer feel normal. This article will review the anatomy and physiology of taste;
      define the different types of taste dysfunction, including the underlying
      pathophysiologic basis related to cancer treatment; and discuss potential nursing
      interventions to manage the consequences of taste dysfunction.

PMID- 22459527
TI  - Knowledge assessment and information needs of oncology nurses regarding inpatient
      medication.
AB  - Although several studies have evaluated the frequency and consequences of
      medication errors, few have explored their causes. In particular, nurses'
      knowledge regarding medications has been evaluated minimally. This survey was
      conducted to determine how nurses master medications prescribed to their patients
      to determine problems nurses may have with prescribed drugs and identify possible
      support tools. A questionnaire was created and presented to nurses in a French
      cancer center. A majority of the respondents correctly identified pharmaceutical
      classes and medications, as well as administration and storage conditions.
      However, side effects, contraindications, and drug-drug interactions were not
      adequately identified. Nurses reported facing problems mainly related to drug
      administration, drug storage, and generic drugs and their therapeutic
      equivalence. Multiple tools are in development to help nurses in these areas.
      This collaborative study between pharmacy and care wards identifies some
      difficulties nurses have regarding drugs and will help to establish improvement
      measures within the hospital.

PMID- 22459528
TI  - Prevention of tumor lysis syndrome in an outpatient setting.
AB  - The prevention and identification of hyperuricemia are critical components in the
      management of tumor lysis syndrome (TLS), which is common in acute leukemias,
      large cell lymphomas, bulky tumors, large tumor burdens, and other cancers with
      high proliferation rates. Such cancers are very receptive to cytotoxic therapy
      because of increased mitotic rates. Lysis of their tumor cells results in
      metabolic abnormalities because of the release of their intracellular products.
      TLS is an oncologic emergency that could lead to renal failure and death;
      therefore, early identification of high-risk patients is vital for successful
      treatment outcomes. Treatment modalities include the use of allopurinol and
      hydration while implementing evidence-based practices for the prevention of TLS
      in the outpatient clinical center.

PMID- 22459529
TI  - Romidepsin: a new drug for the treatment of cutaneous T-cell lymphoma.
AB  - Patients with cutaneous T-cell lymphoma (CTCL) have a rare, disfiguring, and life
      threatening subtype of non-Hodgkin lymphoma primarily localized to the skin.
      Their immune systems are altered and their skin is compromised. In addition, they
      are highly prone to infections-the most common cause of death in patients with
      this disease. Patients presenting with early-stage disease involvement typically
      are treated with topical therapies; patients with advanced-stage and recurrent
      disease require systemic treatment. Specialized knowledge is required by oncology
      healthcare providers to manage the wide array of symptoms experienced by these
      patients as a part of the natural course of this disease. A new drug, romidepsin,
      approved by the U.S. Food and Drug Administration, is indicated in the treatment
      of relapsed CTCL. The authors discuss use of romidepsin in the context of CTCL
      and the information needed to safely administer romidepsin and manage its side
      effects.

PMID- 22459530
TI  - Fertility preservation for patients with cancer.
AB  - A key concern for young patients with cancer and survivors is the desire to
      parent a child. With infertility being a well-established long-term effect of
      many oncologic regimens, patients who want to have children often become
      distressed when faced with the possibility of losing their fertility. Several
      organizations have recommended that oncology professionals discuss options for
      fertility preservation when planning treatment; however, this does not routinely
      occur. Oncology nurses play a significant role in filling this practice gap by
      identifying patients who are interested in future parenting and ensuring they get
      the information and referrals they need to decide whether to pursue fertility
      preservation. This article outlines the available options, challenges in
      discussing fertility, and strategies to incorporate fertility education into
      practice.

PMID- 22459531
TI  - Epstein-Barr virus infection and lymphoproliferative disorder after hematopoietic
      cell transplantation.
AB  - Common herpes viruses such as Epstein-Barr virus (EBV) cause infection and
      disease after hematopoietic cell transplantation (HCT). Post-transplantation
      lymphoproliferative disorder following allogeneic HCT is a rare but life
      threatening disease, mostly associated with EBV-infected B cells. Anti-CD20
      monoclonal antibodies (e.g., rituximab) target normal and infected B cells and
      further suppress the patient's immune system. This article describes the
      development of cellular therapies by infusing virus-specific cytotoxic T
      lymphocytes via IV into patients to create an adoptive immune system for specific
      viral suppression.

PMID- 22459532
TI  - The rise of blogs in nursing practice.
AB  - The number of blogs and related online activities continues to grow exponentially
      each year. Patients increasingly are turning to the Internet for personalized,
      timely, and relevant health information; blogs remain a large source of that
      information. Nurses and other healthcare professionals can harness the
      informational, educational, networking, and supportive power of blogs, as well,
      and should understand how to access and use blogs for professional use.

PMID- 22459533
TI  - Noninvasive interventions for improving well-being and quality of life in
      patients with lung cancer.

PMID- 22459534
TI  - Planting the seeds for an end-of-life journey.

PMID- 22459535
TI  - Treating metastatic breast cancer with systemic chemotherapies: current trends
      and future perspectives.
AB  - Treatment selection for metastatic breast cancer (MBC) is guided by multiple
      factors, most importantly hormone receptor (HR) or HER2 expression, treatment
      history, and prognostic factors such as short disease-free interval, presence of
      visceral metastases, performance status, and degree of symptoms. Chemotherapy is
      indicated as initial therapy for patients with HR-negative disease and following
      failure of hormonal therapies in HR-positive disease. Patients treated with an
      anthracycline or a taxane in early-stage settings may no longer be candidates for
      those drugs in MBC, thus underscoring the need for alternative options.
      Sequential single-agent therapy or combination therapy are viable strategies.
      Trials have shown that ixabepilone plus capecitabine significantly improves
      progression-free survival compared with capecitabine alone in anthracycline- or
      taxane-pretreated or -resistant patients, and single-agent eribulin improves
      survival compared with the physician's choice of treatment in patients treated
      previously with at least two regimens for MBC. Regardless of the regimen,
      proactive management to detect treatment-related adverse events in a timely
      manner remains important for ensuring effective delivery of treatment. Many
      promising investigational agents are in development, including T-DM1 (trastuzumab
      emtansine) and pertuzumab for HER2-positive disease, as well as PARP-1
      (poly[adenosine diphosphate ribose] polymerase-1) inhibitors and cetuximab for
      triple-negative disease. In addition, new options for the treatment of MBC
      following failure of an anthracycline and a taxane promise to improve patient
      outcomes. Nurses should remain vigilant for adverse events and remember that the
      goal of treatment remains control of the disease and palliation.

PMID- 22459536
TI  - Using circulating tumor cells as a prognostic indicator in metastatic castration
      resistant prostate cancer.
AB  - A more reliable tumor marker is needed as a prognostic indicator in metastatic
      castration-resistant prostate cancer. Circulating tumor cells (CTCs) are cells
      that have broken away from a tumor and flow in the bloodstream. Evidence has
      indicated that the presence of CTCs in the peripheral blood of men with solid
      malignancies correlates with clinical outcomes. When the CTC number is reduced to
      fewer than five cells per 7.5 ml of blood, survival outcomes often improve. The
      relationship between the number of CTCs and prognosis has the potential to
      influence treatment decisions. Therefore, oncology nurses and practitioners must
      evaluate the scientific evidence, understand the clinical implications, and
      realize the impact CTC counts may have on practice to effectively communicate the
      CTC results to a patient. In addition, oncology nurses and practitioners must
      know that although favorable changes in CTC count are associated with a better
      prognosis, that alone cannot be used to guide treatment decisions for an
      individual.

PMID- 22459537
TI  - Management of irritant contact dermatitis and peripherally inserted central
      catheters.
AB  - Cutaneous skin changes are common in patients undergoing treatment for cancer.
      However, changes in central line care, maintenance practices, and chemotherapy
      protocols in the early 2000s may have led to the development of a common problem
      of irritant contact dermatitis (ICD) at peripherally inserted central catheter
      (PICC) insertion sites. Repeated exposure to chlorhexidine gluconate topical
      antiseptic solution, used in the general dressing care and maintenance with
      PICCs, may be the leading contributor to the development of ICD at the insertion
      site. A number of additional factors theoretically contribute to the development
      of ICD at the PICC insertion site in patients receiving chemotherapy. In this
      article, ICD will be defined, incidence and potential risk factors will be
      identified, and diagnostic framework will be explored; in addition,
      pathophysiology, onset, presentation, evaluation, and differential diagnosis of
      ICD at PICC sites will be analyzed. Finally, a synopsis of three different
      treatment approaches from healthcare facilities in Canada as well as implications
      for nursing practice and research will be presented.

PMID- 22459538
TI  - Fatigue and disrupted sleep-wake patterns in patients with cancer: a shared
      mechanism.
AB  - The strong and potentially reciprocal relationship between cancer-related fatigue
      (CRF) and disrupted sleep-wake patterns suggests a possible shared physiologic
      pathway. A growing body of evidence supports this and shows that abnormalities in
      the 24-hour rhythm of stress-related hormones may be related to chronic fatigue
      and sleep disturbances. Aberrations in the hypothalamic-pituitary-adrenal (HPA)
      axis, the primary neuroendocrine interface responding to stress, induce important
      biologic and behavioral consequences. HPA aberrations have long been associated
      with chronic fatigue syndrome. Many overlapping symptoms exist between chronic
      fatigue syndrome and CRF, including sleep disruption. Therefore, in the absence
      of knowledge about CRF mechanisms, emerging biologic models from chronic fatigue
      syndrome may assist in understanding the cause of CRF. Cancer-associated
      stressors also may alter the circadian functions of HPA-associated neuroendocrine
      activities, which result in the symptoms of fatigue and disrupted sleep-wake
      patterns in patients with cancer. Exploring promising physiologic models furthers
      the knowledge about CRF and disrupted sleep and may foster hypothesis-based
      studies of mechanisms that underlie apparent overlapping symptoms, providing the
      basis for new management to improve sleep and lessen fatigue.

PMID- 22459539
TI  - Managing immune-related adverse events to ipilimumab: a nurse's guide.
AB  - Ipilimumab is a U.S. Food and Drug Administration-approved novel T-cell
      potentiator that improves survival in metastatic melanoma. Ipilimumab blocks
      cytotoxic T-lymphocyte antigen-4, a negative regulator of the immune response,
      thus promoting T-cell activation and prolonging a patient's antitumor response.
      However, that action may produce a mechanism-related spectrum of immune-related
      adverse events (irAEs), which can become severe and life-threatening if left
      unrecognized and untreated. This article describes the clinical properties of
      ipilimumab, specifically in regard to its unique profile of irAEs. Guidelines to
      manage irAEs are reviewed with a particular emphasis on the contribution of
      nurses to patient care and education. The nurse's role in facilitating
      communication among the oncology team, primary practice team, patients, and
      caregivers is fundamental to early recognition and effective management of irAEs
      so that patients can continue on therapy. As a regular, ongoing presence in
      patient care, the oncology nurse is well placed to deliver information, assess
      patients' understanding of that information, and support them through their
      cancer experience. Checklists of irAE symptoms may be useful for patients and
      nurses alike. In addition, education on ipilimumab's mechanism of action and how
      it contributes to irAEs should form an integral part of the patient treatment
      plan.

PMID- 22459540
TI  - Personal courage paves a course for the future.

PMID- 22459541
TI  - Effect of non-steroidal anti-inflammatory drugs on radiographic spinal
      progression in patients with axial spondyloarthritis: results from the German
      Spondyloarthritis Inception Cohort.
AB  - OBJECTIVE: To investigate the influence of non-steroidal anti-inflammatory drugs
      (NSAIDs) intake on radiographic spinal progression over 2 years in patients with
      ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (SpA).
      METHODS: 164 patients with axial SpA (88 with AS and 76 with non-radiographic
      axial SpA) were selected for this analysis based on availability of spinal
      radiographs at baseline and after 2 years of follow-up and the data on NSAIDs
      intake. Spinal radiographs were scored by two trained readers in a concealed
      randomly selected order according to the modified Stoke Ankylosing Spondylitis
      Spine Score (mSASSS) system. An index of the NSAID intake counting both dose and
      duration of drug intake was calculated. RESULTS: High NSAIDs intake (NSAID
      index>=50) in AS was associated with lower likelihood of significant radiographic
      progression defined as an mSASSS worsening by >=2 units: OR=0.15, 95% CI 0.02 to
      0.96, p=0.045 (adjusted for baseline structural damage, elevated C reactive
      protein (CRP) and smoking status) in comparison with patients with low NSAIDs
      intake (NSAID index<50). This effect was most pronounced in patients with
      baseline syndesmophytes plus elevated CRP: mean mSASSS progression was 4.36+/
      4.53 in patients with low NSAIDs intake versus 0.14+/-1.80 with high intake,
      p=0.02. In non-radiographic axial SpA, no significant differences regarding
      radiographic progression between patients with high and low NSAIDs intake were
      found. CONCLUSION: A high NSAIDs intake over 2 years is associated with retarded
      radiographic spinal progression in AS. In non-radiographic axial SpA this effect
      is less evident, probably due to a low grade of new bone formation in the spine
      at this stage.

PMID- 22459542
TI  - Golimumab in patients with active rheumatoid arthritis who have previous
      experience with tumour necrosis factor inhibitors: results of a long-term
      extension of the randomised, double-blind, placebo-controlled GO-AFTER study
      through week 160.
AB  - OBJECTIVE: The aim of this study was to assess long-term golimumab therapy in
      patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis
      factor alpha (TNFalpha) inhibitor(s) for any reason. METHODS: Results through
      week 24 of this multicentre, randomised, double-blind, placebo-controlled study
      of active RA (>=4 tender, >=4 swollen joints) were previously reported. Patients
      received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group
      3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with <20%
      improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg
      and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab
      50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3
      maintained dosing. Data through week 160 are reported. RESULTS: 459 of the 461
      randomised patients were treated; 236/459 (51%) continued treatment through week
      160. From week 24 to week 100, ACR20 (>=20% improvement in American College of
      Rheumatology criteria) response and >=0.25 unit HAQ (Health Assessment
      Questionnaire) improvement were sustained in 70-73% and 75-81% of responding
      patients, respectively. Overall at week 160, 63%, 67% and 57% of patients
      achieved ACR20 response and 59%, 65% and 64% had HAQ improvement >=0.25 unit in
      Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event
      incidences (95% CI) per 100 patient-years among patients treated with golimumab
      50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious
      infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00
      (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively. CONCLUSION: In
      patients with active RA who discontinued previous TNF-antagonist treatment,
      golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements
      in signs/symptoms and physical function in ~57-67% of patients who continued
      treatment. Golimumab safety was consistent with other anti-TNF agents, although
      definitive conclusions regarding long-term safety require further monitoring.

PMID- 22459543
TI  - Intrapleural instillation of autologous blood for persistent air leak in
      spontaneous pneumothorax in patients with advanced chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: We evaluated the safety and efficacy of increasing doses of
      autologous blood patch pleurodesis in treating persistent air leaks in patients
      with advanced chronic obstructive pulmonary disease (COPD). METHODS: Forty-four
      patients with COPD and spontaneous pneumothorax (SP) on the 7th day after
      intercostal tube drainage were randomly assigned to 4 groups, with 11 patients in
      each group. Groups A, B, and C were given increasing doses of autologous blood-
      ie, 0.5 mL/kg, 1 mL/kg, 2 mL/kg, respectively--whereas group D was given 1 mL/kg
      normal saline only. The procedure was repeated if the air leak persisted on
      postoperative days 9 and 11. Patients in group D crossed over and received
      autologous blood as in group B if the air leak was still present on the 13th
      postoperative day. RESULTS: No patient died in the study. The air leak was sealed
      by the 13th postoperative day only in patients with air leaks smaller than size
      3. Air leaks were classified as 0 to 3 [12], ie, size 0=no air leak; size 1=air
      leak on vigorous coughing only; size 2=small continuous air leak on gentle
      respiration; and size 3=large continuous air leak on gentle respiration. The
      success rates by the 13th postoperative day in groups A, B, C, and D were 27%,
      82%, 82%, and 9%, respectively. The success rate (82%) was significantly higher
      in groups B and C than in group A (p=0.003) and D (p>0.01). CONCLUSIONS: Using
      autologous blood to treat secondary spontaneous pneumothorax (SSP) in patients
      with advanced COPD is easy, safe, and effective. The dose of blood required for
      autologous blood patch pleurodesis should be dependent on the body weight, and 1
      mL/kg blood may be efficient.

PMID- 22459544
TI  - Implantable continuous-flow right ventricular assist device: lessons learned in
      the development of a cleveland clinic device.
AB  - Although the need for right ventricular assist device (RVAD) support for right
      ventricular failure after the implantation of a continuous-flow left ventricular
      assist device has decreased, right ventricular failure still occurs in as many as
      44% of patients after continuous-flow left ventricular assist device insertion.
      Cleveland Clinic's DexAide continuous-flow RVAD was implanted in 34 calves during
      the course of its development. This review discusses lessons learned in the
      design and development of an implantable continuous-flow RVAD that are drawn from
      the results of these in vivo studies, our clinical experience with RVAD support,
      and a review of previously published reports on clinical RVAD use.

PMID- 22459545
TI  - Impact of atrial remodeling on heart rhythm after radiofrequency ablation and
      mitral valve operations.
AB  - BACKGROUND: This study was conducted to determine the effect of left atrial
      structural remodeling on heart rhythm after radiofrequency ablation concomitant
      to mitral valve operation. METHODS: Sixty-six consecutive patients with of atrial
      fibrillation (AF) and mitral valve disease underwent radiofrequency ablation and
      mitral valve operation. Heart rhythm was evaluated before and at 3, 6, and 12
      months postoperatively. Biopsy specimens of the posterior wall of the left atrium
      were evaluated for the extent of fibrosis, myocyte diameter, intensity of
      inflammatory infiltrates, degree of myocytolysis, and capillary density. RESULTS:
      Ten patients died and 1 patient was lost to follow-up. Heart rhythm at 12 months
      was used to divide the remaining 55 patients into two groups: group I, 34 with
      sinus rhythm; group II, 21 with AF. Paroxysmal AF preoperatively was more
      frequent among group I patients, and persistent/long-standing persistent AF in
      group II (p=0.0006). Groups I and II differed significantly in myocyte diameter
      (17.9+/-3.5 vs 20.3+/-4.6 MUm, p=0.04), fibrosis percentage (38.7%+/-11.2% vs
      47.6%+/-12.3%, p=0.009), inflammatory infiltrates (p=0.02), and preoperative left
      atrial diameter (5.03+/-0.7 vs 5.5+/-0.8 cm, p=0.04). No differences were found
      in capillary density (797.9+/-500.6 vs 946.0+/-373.7/mm2, p=0.3) and myocytolysis
      (p=0.4). Multivariate analysis showed myocyte diameter (p=0.047) and fibrosis
      (p=0.014) were independent predictors for an AF persistence at 12 months.
      CONCLUSIONS: Left atrial structural remodeling strongly affects heart rhythm
      after concomitant radiofrequency ablation and mitral valve operation.

PMID- 22459546
TI  - Total arch and descending thoracic aortic replacement by left thoracotomy.
AB  - BACKGROUND: The hybrid treatment of transverse aortic arch pathologies with
      supraaortic debranching and endovascular repair is associated with significant
      morbidity and death and lacks long-term follow-up. The traditional two-stage open
      surgical approach to extensive arch and descending thoracic aneurysms carries a
      significant interval mortality rate. We report the results of a single-stage
      technique of total arch and descending thoracic aortic replacement by a left
      thoracotomy. METHODS: From January 1995 to February 2011, 426 patients underwent
      thoracic or thoracoabdominal aneurysm repair, of which a highly selected group of
      27 patients underwent total arch replacement with descending thoracic or
      thoracoabdominal aortic replacement. All procedures were performed with
      hypothermic circulatory arrest and selective antegrade cerebral perfusion. Two
      patients required transverse division of the sternum. Two patients had emergency
      or urgent operations. Five patients had concomitant coronary artery bypass, and 1
      had concomitant mitral valve replacement. RESULTS: There were no hospital deaths,
      no cerebrovascular accidents, and one instance of transient spinal cord ischemia.
      Three patients had acute renal failure not requiring hemodialysis. Intubation in
      5 patients exceeded 48 hours, and 1 patient needed tracheostomy. Two patients
      required reexploration for postoperative bleeding. Survival at 1, 3, and 5 years
      was 95%, 78%, and 73%, respectively. CONCLUSIONS: Replacement of the total arch
      and descending thoracic aorta by a left thoracotomy provides excellent short-term
      and long-term results for the treatment of extensive arch and thoracic aortic
      pathology, without the need for a second-stage operation. Other cardiac
      pathologies, such as left-sided coronary disease and mitral valve disease, can be
      addressed concurrently.

PMID- 22459547
TI  - Arterial switch operation in the first hours of life using autologous umbilical
      cord blood.
AB  - BACKGROUND: In this study, we analyzed our clinical experience performing the
      arterial switch operation in the first hours of life using autologous umbilical
      cord blood transfusion (AUCBT). The safety and efficiency of AUCBT was assessed
      and compared with surgery with the use of homologous blood transfusion. METHODS:
      Between September 2009 and February 2011, 61 neonates underwent ASO at our
      institution. Patients were enrolled and allocated to two groups with different
      modalities of management strategies for neonates with dextrotransposition of the
      great arteries. RESULTS: The groups were similar in diagnoses, birth weight,
      cardiopulmonary bypass protocol, and surgical technique, excepting timing of
      surgery and blood management strategy. Preoperative mean hematocrit did not
      differ significantly between the groups (45% versus 45%). Mean hematocrit was
      significantly lower in the study group than in the control group during
      cardiopulmonary bypass (24% versus 31%). The hematocrit progressively increased
      in the study group to 38% on the first postoperative day. Serum lactate levels
      were higher in the study group till the second day after surgery. There were no
      significant differences in postoperative clinical profiles. There were no
      hospital deaths and no AUCBT-related side effects in our study. CONCLUSIONS: The
      arterial switch operation can be performed in the first hours of life with AUCBT.
      Therefore, AUCBT is a safe and an efficient alternative to homologous blood in
      neonatal open heart surgery. During the study, we also identified positive
      economic effects associated with this approach.

PMID- 22459548
TI  - Defining and refining 5-HT receptor targets for migraine.

PMID- 22459550
TI  - Audiological monitoring for ototoxic tuberculosis, human immunodeficiency virus
      and cancer therapies in a developing world setting.
AB  - Ototoxic drugs are widely used in the developing world, without audiological
      monitoring. Epidemiological data on ototoxic deafness are lacking for developing
      countries. The public health aspect of ototoxicity is often overlooked, to the
      detriment of the individual patient. This paper reviews ototoxic hearing loss,
      particularly in sub-Saharan Africa, and also assesses the impact of treatments
      for tuberculosis, cancer and human immunodeficiency virus (the latter including
      highly active antiretroviral therapy) on ototoxic hearing loss. The paper also
      discusses obstacles to audiological monitoring for ototoxicity in the developing
      world, and the potential of audiology screening using applications for mobile
      devices.

PMID- 22459549
TI  - Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for
      the acute treatment of migraine: a phase 2 randomised, placebo-controlled,
      parallel-group, dose-ranging study.
AB  - BACKGROUND: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5
      HT(1F) receptor agonist without vasoconstrictor activity that seemed effective
      when given as an intravenous infusion in a proof-of-concept migraine study. We
      aimed to assess the efficacy and safety of oral lasmiditan for the acute
      treatment of migraine. METHODS: In this multicentre, double-blind, parallel
      group, dose-ranging study in 43 headache centres in five European countries,
      patients with migraine with and without aura and who were not using prophylaxis
      were randomly assigned (1:1:1:1:1) to treat one moderate or severe attack at home
      with 50 mg, 100 mg, 200 mg, or 400 mg lasmiditan, or placebo. Study drug and
      placebo were supplied in identical numbered tablet packs. The randomisation code
      was generated by an independent statistician. Patients and investigators were
      masked to treatment allocation. The primary endpoint was dose response for
      headache relief (moderate or severe becoming mild or none) at 2 h. The primary
      analysis was done in the modified intention-to-treat population. This study is
      registered with ClinicalTrials.gov, number NCT00883051. FINDINGS: Between July 8
      2009, and Feb 18, 2010, 512 patients were randomly assigned to treatment, 391 of
      whom received treatment. 86 patients received placebo (81 included in primary
      analysis) and 305 received lasmiditan (50 mg n=79, 100 mg n=81, 200 mg n=69, and
      400 mg n=68 included in primary analysis). There was a linear association between
      headache response rate at 2 h and lasmiditan dose (Cochran-Armitage test
      p<0.0001). Every lasmiditan treatment dose significantly improved headache
      response at 2 h compared with placebo (lasmiditan 50 mg: difference 17.9%, 95% CI
      3.9-32.1, p=0.022; 100 mg: 38.2%, 24.1-52.4, p<0.0001; 200 mg: 28.8%, 9.6-39.9,
      p=0.0018; 400 mg: 38.7%, 23.9-53.6, p<0.0001). The proportion of patients with
      treatment-emergent adverse events increased with increasing doses (53/82 [65%],
      59/82 [72%], 61/71 [86%], and 59/70 [84%] for lasmiditan 50, 100, 200, and 400
      mg, respectively vs 19/86 [22%] for placebo). Most adverse events were mild or
      moderate in intensity, with 16 of 82 (20%), 23 of 82 (28%), 28 of 71 (39%), and
      31 of 70 (44%) of patients on lasmiditan 50, 100, 200, and 400 mg, respectively
      reporting a severe adverse event compared with five of 86 (6%) on placebo. The
      most common adverse events were CNS related and included dizziness, fatigue,
      vertigo, paraesthesia, and somnolence. INTERPRETATION: Oral lasmiditan seems to
      be safe and effective in the acute treatment of migraine. Further assessment in
      larger placebo-controlled and triptan-controlled trials are needed to assess the
      potential role of lasmiditan in acute migraine therapy. FUNDING: CoLucid
      Pharmaceuticals.

PMID- 22459551
TI  - Trends and risk factors of hypercholesterolemia among Kuwaiti adults: National
      Nutrition Surveillance Data from 1998 to 2009.
AB  - OBJECTIVE: To determine temporal changes in hypercholesterolemia prevalence and
      associated factors in Kuwaiti adults. DESIGN: Analysis of nationally
      representative cross-sectional population survey data from the Kuwait National
      Nutrition Surveillance. METHODS: A total of 15,110 men and 17,701 women, aged 20
      69 years, registered for employment or pensions, Hajj Pilgrimage health checkups,
      or were parents accompanying their children for immunization from 1998 through
      2009. Sociodemographic and lifestyle information, height and weight, and blood
      samples were collected. RESULTS: Hypercholesterolemia (HC; serum cholesterol
      >=5.20 mmol/L) prevalence increased within the time period until 2006-2007 (men,
      56.0%; women, 53.6%), except for 2002-2003, and then declined significantly in
      both men (33.7%) and women (30.6%). Linear and logistic regression adjusted for
      age, education level, and body mass index (BMI) also showed a significant upward
      temporal trend for total cholesterol and prevalence of moderate and high HC
      (except for high HC in men) until 2004-2007 followed by a significant downward
      trend in 2008-2009 in both men and women. For both genders, age, BMI, education
      level, and presence of diabetes were significantly independently associated with
      high HC, whereas only age and BMI were associated with moderate HC. Female
      smokers, compared with non-smokers, had significantly higher odds ratios for both
      moderate and high HC. Current exercise or fruit and vegetable intake showed no
      significant association for either gender. CONCLUSION: Continued monitoring of
      serum cholesterol is needed to see if the negative trend observed in 2008-2009
      endures and further research of contributing factors is required for the
      development of targeted intervention strategies.

PMID- 22459552
TI  - The significance of folate deficiency in alcoholic and nutritional neuropathies:
      analysis of a case.
AB  - OBJECTIVE: To elucidate the significance of folate deficiency in alcoholic and
      nutritional neuropathies. METHODS: We preformed a comprehensive clinical
      screening of a patient with chronic alcoholism who manifested neuropathy,
      macrocytic anemia, liver dysfunction, and folate deficiency. RESULTS: A 33-y-old
      woman with chronic alcoholism presented with acutely progressive glove- and
      stocking-type sensorimotor polyneuropathy. Although an episode of neuropathy
      preceded the current episode by 2 y, its cause was never determined. The findings
      of nerve conduction studies were indicative of axonal neuropathy. Laboratory
      findings revealed macrocytic anemia and liver dysfunction. Her serum level of
      folate was reduced, whereas thiamine, riboflavin, and cobalamin levels were
      within normal range. The neuropathy and anemia showed gradual recovery after the
      initiation of folic acid supplementation. CONCLUSIONS: This case study indicates
      that folate deficiency should be monitored closely in patients with chronic
      alcoholism and associated malnutrition. Additionally, folate deficiency should be
      considered as a differential diagnosis of neuropathy.

PMID- 22459553
TI  - Association between interaction and ratio of omega-3 and omega-6 polyunsaturated
      fatty acid and the metabolic syndrome in adults.
AB  - OBJECTIVE: To investigate the association of the intakes of omega-3 (including
      alpha-linolenic acid [ALA], eicosapentaenoic acid [EPA] plus docosahexaenoic acid
      [DHA]) and omega-6 polyunsaturated fatty acids (PUFAs), the interaction, and the
      ratio of these PUFAs with the metabolic syndrome (MetS) in adults. METHODS: This
      cross-sectional study was conducted in a random sample of participants (n = 2451,
      19-84 y old) in the Tehran Lipid Glucose Study. Dietary intake was assessed using
      a validated semiquantitative food-frequency questionnaire. Anthropometric
      characteristics, blood pressure, and fasting plasma concentrations of glucose and
      lipids were measured. The MetS was defined according to the Adult Treatment Panel
      III guidelines. RESULTS: Among the PUFAs, the ALA and omega-6 PUFA intakes were
      inversely associated with the MetS. Subjects in the highest quartile of ALA and
      omega-6 fatty acid intakes had a 38% (odds ratio 0.62, 95% confidence interval
      0.41-0.95) and a 0.47% (odds ratio 0.53, 95% confidence interval 0.31-0.89) lower
      prevalence of MetS, respectively, compared with those in the lowest quartile. The
      dietary ratio of omega-6 to omega-3 fatty acids was not associated with the MetS.
      When the interaction between ALA and omega-6 fatty acid was assessed, the ALA
      intake was associated with a lower prevalence of the MetS, without modification
      by the omega-6 PUFA intake. Subjects with at least the median ALA intake (1084
      mg/d) had a lower prevalence of the MetS, irrespective of an omega-6 PUFA intake
      lower or higher than the median compared with subjects with intakes below the
      median for both. CONCLUSION: The ALA intake was inversely associated with the
      MetS, irrespective of the background intake of omega-6 PUFAs, in adults.

PMID- 22459554
TI  - The need to identify and effectively manage nutritional concerns in patients
      undergoing treatment for substance abuse.

PMID- 22459555
TI  - Intake of dairy calcium and tooth loss among adult Danish men and women.
AB  - OBJECTIVE: To investigate whether gender differences in tooth loss are influenced
      by caries risk and sources of dietary calcium intake. METHODS: This was a cohort
      study that included 432 Danish adults (30-60 y old) with information on dietary
      calcium intake in 1982 and 1983 and tooth loss from 1987 and 1988 through 1993
      and 1994. Total calcium intake, estimated by a 7-d food record or a a diet
      history interview, was divided into dairy and non-dairy forms of calcium.
      RESULTS: In men, a 10-fold increase in dairy calcium intake was significantly
      associated with a decreased risk of tooth loss (incidence-rate ratio 0.32, 95%
      confidence interval 0.15-0.68) even after an adjustment for tooth count in 1987
      and 1988, age, education, and civil status (model 1), smoking, alcohol
      consumption, sucrose intake, and use of vitamin and/or mineral supplements (model
      2), time since last dental visit and the presence of oral dryness (model 3), and
      a high Lactobacillus count (model 4). In women, dairy calcium was not
      statistically associated with tooth loss in the crude and adjusted models (models
      1 to 3). However, the association became highly significant once the
      Lactobacillus count was included in model 4 (incidence-rate ratio 0.25, 95%
      confidence interval 0.09-0.73). Non-dairy calcium was not associated with tooth
      loss in men and women in the fully adjusted models. CONCLUSION: Dietary calcium
      intake, particularly calcium from dairy products, seems to protect against loss
      of teeth in adult men and women. The previous gender differences found in the
      relation between calcium intake and tooth loss may be the result of differences
      in the caries risk between genders.

PMID- 22459556
TI  - Rare case of a large mediastinal cyst involved in Hodgkin's lymphoma.
AB  - We report a case of a mediastinal cystic retrosternal process, discovered by
      magnetic resonance imaging (MRI) in a 19-year-old male patient, with unusual
      inhomogenous signals in both T1- and T2-weighted images and contrast-enhancing
      septation. Macroscopically, the tumor weighed 1330 g, and was constituted by one
      dominating cyst measuring 14 cm in diameter. Additional small cysts were seen
      microscopically. The cystic wall was continuously infiltrated by nodular
      sclerosing Hodgkin's lymphoma, also affecting adjacent lymph-nodes. Age and sex
      of the patient and the diagnosed subtype of Hodgkin's lymphoma are in line with
      previously reported rare cases of mediastinal cysts with Hodgkin's lymphoma. The
      cyst reported here, most likely a secondary thymic cyst, is larger than those
      reported before. The main reason for the development of these cysts might be the
      accompanying inflammation of the lymphoma. Little is known about the imaging
      features of mediastinal cysts caused by lymphoma. Plain thymic cysts are normally
      homogenous on T1- and T2-weighted images. Hodgkin's lymphoma might be homogenous
      on T1-weighted images and is mostly inhomogenous on T2-weighted images. In case
      of inhomogenous cysts with contrast-enhancing septation, one should consider the
      diagnosis of an associated neoplasm.

PMID- 22459557
TI  - Adherence to therapeutic hypothermia guidelines for out-of-hospital cardiac
      arrest.
AB  - BACKGROUND: Out of hospital cardiac arrest is associated with a high rate of
      mortality, and poor neurological outcomes. Favourable neuro-protective effects
      are associated with induced hypothermia and international recommendations exist
      for therapeutic hypothermia. OBJECTIVE: This study reviews practice for
      therapeutic hypothermia for out of hospital cardiac arrest patients within one
      ICU. It aims to describe the level of adherence to the guideline, identify
      barriers to implementation and to improve adherence. SETTING: This project was
      conducted in an adult ICU which admits 2000 patients yearly. METHODS: A
      retrospective chart audit was used to document practice for a 12 month period.
      RESULTS: 33 patients were admitted to the ICU with a diagnosis of out of hospital
      cardiac arrest and met study inclusion criteria. From this sample of 33 patients,
      four patients (12%) were at the goal temperature of 32.5-33.5  degrees C, in the
      target time of 2h. Nearly half (n = 17) were not cooled at all. The length of
      time the patient was in the ICU prior to active cooling commencing varied from <1
      h (n = 15, 45%) to >3 h (n = 5, 15%). Twenty-four percent (n = 9) were cooled for
      the recommended length of time. There were medical orders stating a target
      temperature in nearly half of the cases (n = 18), however, only 27% (n = 9) were
      consistent with the ICU guidelines. A number of strategies have been initiated.
      They aim to improve communication and ready access to the required materials.
      CONCLUSIONS: The audit indicated that less than a third of the patients
      experienced therapeutic induced hypothermia and only 12% were at goal temperature
      within the required 2 h. Strategies initiated to improve guideline implementation
      included; regular education sessions with ICU staff; placing a cooling blanket on
      the bed prior to admitting a patient post OOHCA; improving ready access to
      cooling agents and the addition of a care path for the induction and maintenance
      of therapeutic hypothermia to support and prompt clinicians when using the
      computerised patient record system.

PMID- 22459558
TI  - Evaluation of multiplex polymerase chain reaction and microarray-based assay for
      rapid herpesvirus diagnostics.
AB  - Rapid diagnosis is critical to minimize morbidity and mortality associated with
      infections of the central nervous system (CNS). In this study, we evaluated the
      performance of a multiplex polymerase chain reaction (PCR) and microarray-based
      method, Prove-itTM Herpes, in a routine clinical laboratory setting for the
      diagnostics of 7 herpesviruses in viral CNS infections. Cerebrospinal fluid
      samples (n = 495), which had arrived for diagnostics in the 5 participating
      laboratories, were analyzed for herpesvirus DNA both by the current PCR-based
      method of the laboratory and by the microarray assay. The sensitivity and
      specificity for the microarray assay were 93% and 99%, respectively. The
      microarray assay was considered as a rapid and robust diagnostic platform that
      was easily implemented into the laboratory workflow. The broad herpesvirus
      coverage and the small sample volume required by the assay could benefit the
      diagnostics and thus the treatment of life-threatening infections of the CNS,
      especially among immunocompromised patients.

PMID- 22459559
TI  - Effects of modality on memory for original and misleading information.
AB  - This study examined the role of modality in correct recognition and
      misinformation acceptance in a naturalistic event cognition task that reflected
      an everyday life sequence of events. Participants heard, observed or acted out a
      sequence of events and were tested on memory for these events after being
      presented with an accurate description of the events or a description containing
      misinformation. The results indicated that recognition of unaltered information
      was higher in the enactment condition than the auditory or visual conditions and
      that this effect persisted over time. Misinformation acceptance for the immediate
      recognition test was lowest in the auditory condition but this advantage
      disappeared over time. Modality congruence of the auditory condition with the
      modality in which misinformation was presented and different retrieval processes
      underlying recognition of altered and unaltered information may explain these
      findings.

PMID- 22459560
TI  - Investigating the role of attentional resources in the irrelevant speech effect.
AB  - Irrelevant words can be disruptive to performance, and the frequency of usage of
      the irrelevant words has affected the magnitude of such disruption (Buchner &
      Erdfelder, 2005). The finding of word frequency differences in the magnitude of
      the irrelevant speech effect (ISE) implicated a role for attentional processes.
      Using a different conceptualization of attention, researchers have found that
      individual differences in working memory capacity did not predict the magnitude
      of the ISE, which questioned the role of attentional control (Beaman, 2004;
      Sorqvist, 2010). The current study investigated aspects of the construct of
      attention and the ISE, using both individual and developmental difference
      approaches. Results showed no significant difference between serial recall
      performances in the presence of high or low word frequency distractors.
      Furthermore, effects of working memory capacity differences were not found, but
      children displayed a larger ISE than college students. The weight of the evidence
      appears against an attentional resource view of the ISE.

PMID- 22459561
TI  - US specificity of occasion setting: hierarchical or configural learning?
AB  - Four experiments in rats examined whether occasion setters and target CSs play
      qualitatively different roles in occasion-setting discriminations. Two visual
      occasion setters, A and B, signalled reinforcement of two auditory target CSs, x
      and y, with sucrose and oil (A...x->suc, B...y->oil, A-, B-, x-, y-); in addition
      two transfer CSs w and z were paired with sucrose and oil (w->suc, z->oil). When
      w and z were substituted for x and y (A...w, B...w, A...z, B...z) more responding
      was observed when both stimuli had been paired with the same outcome (Experiments
      1 and 3a). No effect was observed when two visual "pseudo-occasion setters", C
      and D (paired with sucrose and oil in a trace relation to the US:C...->suc, D...
      >oil), were substituted for the occasion setters A and B (C...x, D...x, C...y,
      D...y; Experiments 2, 3b and 4). These results could not be explained in terms of
      Pavlovian summation: responding to combinations of Pavlovian CSs paired with same
      or different outcomes was either the same, or lower when both stimuli had been
      paired with the same outcome (Experiment 4). Implications of these results for
      theories of occasion setting and configural learning are discussed.

PMID- 22459562
TI  - Deep brain stimulation in disabling involuntary vocalization associated with
      Huntington's disease.

PMID- 22459563
TI  - Association between PLA2G6 gene polymorphisms and Parkinson's disease in the
      Chinese Han population.
AB  - The PLA2G6 gene encodes a group VIA calcium-independent phospholipase A(2), and
      has been suggested as the causative gene for autosomal recessive dystonia
      parkinsonism. We conducted a case-control study using 531 mainland Chinese
      Parkinson's disease (PD) patients and 561 healthy controls, and genotyped 4 tag
      single nucleotide polymorphisms (SNPs) of the PLA2G6 gene: rs4375, rs2267369,
      rs132985, and rs2284063. Logistic regression analysis revealed no difference in
      genotype or allele frequencies for any of the SNPs between the sporadic PD group
      and control group. Similarly, comparison of SNPs in patients with either early
      onset (EOPD, <= 50 years) or late-onset (>50 years) PD revealed no statistical
      differences from controls. We detected no significant association of the 4 SNPs
      with PD at the genotypic level, after adjustment for age. The rs132985 genotype
      frequency showed a difference in male patients but not in female patients, but
      the P value did not survive Bonferroni correction (Pcorr = 0.068). We found that
      the rs132985 A-rs2284063 C haplotype is marginally associated with increased risk
      of developing PD (P = 0.048) after 10,000 permutations. These findings suggest
      that PLA2G6 is not a susceptibility gene for PD in our population. However, a
      broader examination and a replication of this study in other populations are
      needed.

PMID- 22459564
TI  - Nigro-striatal involvement in primary progressive freezing gait: insights into a
      heterogeneous pathogenesis.
AB  - Primary progressive freezing gait (PPFG) is a clinical syndrome underlain by
      diverse neurodegenerative diseases and characterized by early occurrence of gait
      freezing. Either degeneration or integrity of the nigrostriatal terminals have
      been found by SPECT and PET studies. In this retrospective study, we evaluated
      (123)I-FP-CIT SPECT findings in a consecutive series of 13 PPFG patients with
      detailed clinical evaluation over time (mean follow-up duration: 3.1 +/- 1.2
      years). In all patients, (123)I-FP-CIT SPECT has been performed at the time of
      first clinical evaluation (1.7 +/- 1.4 years after disease onset) and was
      compared with data from 23 age- and sex-matched healthy subjects. PPFG patients
      were categorized as having abnormal (n = 8) or normal (n = 5) SPECT. At disease
      onset, PPFG with abnormal SPECT had more frequent hypophonia, higher UPDRS-III
      scores and partial levodopa responsiveness. By contrast, PPFG with normal SPECT
      had more frequent bilateral plantar responses and no response to levodopa. At
      latest follow-up, initial diagnosis in the abnormal SPECT group was revised (n =
      5) to progressive supranuclear palsy (n = 4) and pure akinesia with gait freezing
      (n = 1). Among the five patients with normal SPECT, follow-up evaluation
      disclosed corticobasal syndrome (n = 2) and primary lateral sclerosis (n = 1).
      Dopamine transporter imaging can capture the clinical heterogeneity of PPFG and
      might have a value to predict possible disease progression.

PMID- 22459565
TI  - Phase II study of sirolimus in treatment-naive patients with advanced
      hepatocellular carcinoma.
AB  - BACKGROUND: Rapalogs are emerging as promising targeted anticancer drugs.
      Activation of the PI3K/Akt/mTOR pathway has been observed in 15-50% of
      hepatocellular carcinomas. METHODS: In this phase II study, patients with
      advanced hepatocellular carcinoma and underlying cirrhosis received sirolimus (20
      mg/week for 1 month then 30 mg/week). Tumour response was assessed every 8 weeks.
      The primary endpoint was the objective tumour response rate according to the
      Response Evaluation Criteria in Solid Tumours criteria. Secondary endpoints
      included the objective response according to the modified Response Evaluation
      Criteria in Solid Tumours criteria, safety, and pharmacokinetic parameters.
      RESULTS: Twenty-five patients received sirolimus for a median of 20.6 weeks. Two
      patients had an objective response (8%, 95CI: 0.98-26.03), including one complete
      response, and 8 patients had stable disease. There were 2 cases of grade 5
      toxicity (infections) and 5 cases of grade 3 toxicity. The main grade 1/2
      toxicity was mild transient fatigue (76%). Median time to radiological
      progression and overall survival were 15.3 weeks (range: 8.2-173.9) and 26.4
      weeks (range: 8.2-173.9) respectively. Use of the modified Response Evaluation
      Criteria in Solid Tumours criteria did not identify any further responders.
      CONCLUSION: These data suggest that first-line sirolimus shows antitumoural
      efficacy in advanced hepatocellular carcinoma. Larger trials with Child A
      patients are needed.

PMID- 22459566
TI  - Endoscopic ultrasound image of hydatid membranes in the common bile duct.

PMID- 22459567
TI  - Comment to "Precut sphincterotomy, repeated cannulation and post-ERCP
      pancreatitis in patients with bile duct stone disease".

PMID- 22459568
TI  - Study of survivin and X-linked inhibitor of apoptosis protein (XIAP) genes in
      acute myeloid leukemia (AML).
AB  - Apoptosis deregulation is important for cancer development, chemotherapy
      response, and prognosis. Survivin and X-linked inhibitor of apoptosis protein
      (XIAP) are 2 members of the inhibitor of apoptosis proteins family (IAP). We used
      semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to
      determine the levels of expression of survivin and XIAP in 30 patients with de
      novo acute myeloid leukemia (AML) and 20 age- and sex-matched healthy volunteers.
      Survivin and XIAP overexpression were detected in 36.7% and 43.3% of cases,
      respectively. Patients with overexpression of either survivin or XIAP showed
      unfavorable response to chemotherapy in 81.2% and 91.7%, respectively. Also,
      these cases showed shorter median survival time (30 days) compared to patients
      with normal expression of either survivin or XIAP (150 days and 180 days).
      Patients with overexpression of both survivin and XIAP showed unfavorable
      response to induction therapy in 100% of the patients and the shortest median
      survival (30 days). These findings suggest that survivin and XIAP may have a role
      in leukemogenesis and provide prognostic information.

PMID- 22459569
TI  - [Improvements in the treatment of T-cell acute lymphoblastic leukemia in
      children].

PMID- 22459570
TI  - [Implication of progesterone in vasomotor reactions of menopause and its relation
      with cardiovascular risk].

PMID- 22459571
TI  - [Colchicine: what's up, doc?].
AB  - Over de past years use off-label of colchicine has notably increased, mainly as a
      result of the latest studies published about its efficacy in the prevention of
      recurrence after acute or recurrent pericarditis and pericarditis after cardiac
      surgery. Nevertheless, colchicine use has been associated with serious drug
      interactions and toxicity with high morbimortality. Taking into account the
      recent results about the efficacy of colchicine in pericarditis management, we
      envisage an increase in the use of this drug by clinicians. In this review we
      analyse the risks and current recommendations for a safety use of this ancient
      drug.

PMID- 22459572
TI  - [Continuity of care in polypathological patient].

PMID- 22459574
TI  - [Effect of flavonoids in the prevention of lung cancer: systematic review].
AB  - For years, lung cancer has been the tumor causing more deaths in industrialized
      and emerging countries. A meticulous care of the nutritional aspects, with
      emphasis on high consumption of fruits and vegetables, can be an important
      element of primary prevention. Taking into account research on the effect of
      substances with antioxidant power, many epidemiological studies have focused on
      flavonoids. The objective of this review is to analyze the available scientific
      evidence in the literature regarding the role of flavonoids in lung cancer. After
      a systematic literature review, we identified a meta-analysis, a systematic
      review, 11 prospective cohort studies and 5 case-control studies. After reviewing
      the scientific evidence provided by these works, there was a small protective
      effect of flavonoid consumption (especially at high doses) against the
      development of lung cancer, although not all studies confirmed it. There seems to
      be no differences between selective intake of different types of flavonoids and
      consumption of total flavonoids, but there are differences between the different
      populations studied.

PMID- 22459573
TI  - [T-cell pediatric acute lymphoblastic leukemia: analysis of survival and
      prognostic factors in 4 consecutive protocols of the Spanish cooperative study
      group SHOP].
AB  - BACKGROUND AND OBJECTIVES: Acute lymphoblastic leukemia (ALL) is the most
      frequent cancer in childhood, with cure rates of 80-85%. In T-cell ALL (15% of
      ALL), prognostic factors are ill defined. We aimed to describe the event-free
      survival (EFS) and analyze clinical prognostic factors in a series of pediatric T
      ALL of 4 consecutive clinical trials. PATIENTS AND METHODS: Children with T-ALL
      aged 1-18 years treated in 37 institutions in Spain were enrolled in 4
      consecutive trials from February-1989 to November-2009. RESULTS: A total of 218 T
      ALL patients out of 1,652 pediatric ALL were evaluable during the study period
      (SHOP/ALL-89: 35, ALL-94: 63, ALL-99: 62, ALL-2005: 58). There were 164 boys
      (75%). Median age (years) was 7.8 range (1.3-18.6). Median leukocytes (10(9)/L)
      was 78.2, range 0.8-930. Fifteen (6.8%) children had central nervous system (CNS)
      involvement at diagnosis. Regarding response to induction treatment, 150 (75%)
      patients had less than 5% blasts on day-14 bone marrow and 199 achieved complete
      remission at the end of induction. Overall survival (OS) at 60 months for
      SHOP/ALL-89, ALL-94, ALL-99 was 48 (8), 49 (6), 70 (6) %, respectively, and at 48
      months for SHOP/ALL-2005 (ongoing protocol) was 74 (8) %. Median follow-up
      (months) was 206, 152, 74 and 17 respectively. Analysis of prognostic factors
      revealed no statistical differences regarding sex or age. Leukocyte count over
      200*10(9)/l (P=.024), CNS infiltration at diagnosis (P<.006) and treatment
      response had prognostic significance (end-induction complete remission)
      (P=.0000), day 14-bone marrow (P=.005). CONCLUSIONS: Results for the SHOP/ALL-89
      and ALL-94 protocols were inferior to other contemporary protocols but there has
      been an improvement in survival in the 2 last trials. In line with other T-ALL
      series, response to treatment had the strongest prognostic impact.

PMID- 22459575
TI  - [Identification of clinical features and laboratory abnormalities associated with
      the development of vertebral fractures in women with postmenopausal
      osteoporosis].
AB  - BACKGROUND AND OBJECTIVE: Vertebral fractures (VF) are a major risk factor for
      the development of further fractures. Therefore, it is important to identify
      clinical risk factors and laboratory abnormalities related to VF. We aimed to
      analyse clinical and biochemical alterations related to the presence of
      radiological VF in postmenopausal women with osteoporosis. PATIENTS AND METHODS:
      Two-hundred and four postmenopausal women with osteoporosis (aged 64,9 [10]
      years) who were referred to an outpatient Rheumatology Unit were prospectively
      included. Bone mineral density (BMD), spine X-ray, and laboratory tests were
      performed in all participants before treatment. RESULTS: Twenty-eight per cent of
      patients had VF. Comparing women with and without VF, those with fractures were
      older (71.9 [10] vs 61.8 [8,6], P<.001), had lower stature (152 [7.2] vs 155
      [6.2], P=.01), lower total hip T-score values (-2.2 [0,9] vs -1.9 [0.8], P=.041),
      higher prevalence of non-VF (38 vs 30%, P=.04) and a higher prevalence of low
      serum 25(OH)D levels (69 vs 53%, P<.05). In logistic regression analysis, age and
      BMD at the total hip were independent predictors of VF. Patients over 65
      presented a higher frequency of VF (47 vs 12%, P<.0001). In addition, a T-score
      lower than -2,5 at the total hip was associated with an increased risk of VF (OR
      2.5; 95% CI 1.2-4.9). CONCLUSIONS: Over the age of 65 nearly half of the
      postmenopausal women with osteoporosis have VF and a higher prevalence of low
      25(OH)D serum measurements. Spinal X-ray and 25(OH)D serum measurements are
      especially indicated in this group of women since it influences the therapeutic
      approach.

PMID- 22459576
TI  - [Hand hygiene for a safer care].

PMID- 22459577
TI  - [Clinical impact of laboratory critical values notification as a tool for patient
      safety].

PMID- 22459578
TI  - Preface: the neural crest--from stem cell formation to migration and
      differentiation.

PMID- 22459579
TI  - Can "early" and "late"18F-FDG PET-CT be used as prognostic factors for the
      clinical outcome of patients with locally advanced head and neck cancer treated
      with radio-chemotherapy?
AB  - PURPOSE: To evaluate the prognostic value of "early" and "late" Fluorine-18
      Fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography
      (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) treated
      with radio-chemotherapy (RTCT). MATERIALS AND METHODS: Twenty-six patients
      treated with RTCT for HNSCC were included. All patients underwent (18)F-FDG PET
      CT at baseline ("staging" PET-CT), after 2 weeks of treatment ("early" PET-CT)
      and 8-12 weeks after treatment ("late" PET-CT). Changes in FDG uptake in the
      primary tumor (T) and lymph nodes (N) were correlated with local and regional
      control, respectively; overall metabolic response was correlated with relapse
      free survival (RFS) and disease specific survival (DSS). RESULTS: After a median
      follow-up of 29.2 months, 19/26 patients were living and 17/19 had no evidence of
      disease. When comparing "staging", "early" and "late" PET results, a significant
      decrease of FDG SUV(max) in T and N was documented. When correlating changes in
      FDG uptake in T and N with local and regional control, a statistically
      significant correlation only with the "late" reduction was found. Statistical
      analysis failed to demonstrate any correlation between the "early" metabolic
      response and the patient clinical outcome while the "late" metabolic response
      revealed a strong correlation with RFS (p = 0.01) and DSS (p = 0.009).
      CONCLUSIONS: In patients with HNSCC, PET-CT performed after RTCT predicts the
      clinical outcome, since it strongly correlates with RFS and DSS. On the other
      hand, the predictive role of "early" metabolic response was not confirmed by this
      study.

PMID- 22459580
TI  - Characterization of chicken melanoma differentiation-associated gene 5 (MDA5)
      from alternative translation initiation.
AB  - The present study was undertaken to identify and characterize chicken melanoma
      differentiation-associated gene 5 (MDA5) from alternative translation initiation.
      The alternatively translated chicken MDA5 had an open reading frame of 3309 base
      pairs, shorter than the predicted chicken MDA5 sequence by 549 base pairs and
      longer than the recently published chicken MDA5 (GU570144) by 303 base pairs. The
      domain architecture was conserved among MDA5 molecules from various vertebrates.
      The alternatively translated chicken MDA5 shared high genetic identity to
      zebrafinch MDA5, but not to fish or mammalian MDA5. Various concentrations of
      chicken MDA5 transcripts were detected in different chicken tissues, with the
      highest concentration found in the intestine (1.4*10(10)copy/mg tissue). Chicken
      interferon (IFN-beta) expression was dependent on the dose of pCDNA3.1-MDA5-long
      transfection in DF1 cells without double-stranded RNA stimulation. DF1 cells
      transfected with polyinosinic-polycytidylic acid (poly(I:C)) had significantly
      (p<0.05) increased fold changes in chicken MDA5 and IFN-beta mRNA expression as
      compared to those in the controls. DF1 cells incubated with poly(I:C) did not
      have significant (p>0.05) changes in mRNA expression of chicken MDA5 and IFN
      beta. Chicken MDA5 mRNA level did not change significantly (p>0.05) in DF1 cells
      treated with imiquimod or bacterial DNA. The results indicate that although
      chicken MDA5 is phylogenetically different from mammalian MDA5, the domain
      architecture remains conserved. Chicken MDA5 can be detected in various tissues
      and functions to signal the activation of chicken IFN-beta when overexpressing or
      being stimulated by poly(I:C).

PMID- 22459581
TI  - Multiplexed detection of cardiac biomarkers in serum with nanowire arrays using
      readout ASIC.
AB  - Early detection of cardiac biomarkers for diagnosis of heart attack is the key to
      saving lives. Conventional method of detection like the enzyme-linked
      immunosorbent assay (ELISA) is time consuming and low in sensitivity. Here, we
      present a label-free detection system consisting of an array of silicon nanowire
      sensors and an interface readout application specific integrated circuit (ASIC).
      This system provides a rapid solution that is highly sensitive and is able to
      perform direct simultaneous-multiplexed detection of cardiac biomarkers in serum.
      Nanowire sensor arrays were demonstrated to have the required selectivity and
      sensitivity to perform multiplexed detection of 100 fg/ml troponin T, creatine
      kinase MM, and creatine kinase MB in serum. A good correlation between
      measurements from a probe station and the readout ASIC was obtained. Our
      detection system is expected to address the existing limitations in cardiac
      health management that are currently imposed by the conventional testing
      platform, and opens up possibilities in the development of a miniaturized device
      for point-of-care diagnostic applications.

PMID- 22459582
TI  - Application of creatinine-sensitive biosensor for hemodialysis control.
AB  - The highly sensitive and selective potentiometric biosensor for creatinine
      determination has been developed by us earlier. In it, pH-sensitive field effect
      transistors were used as transducer and immobilized creatinine deiminase (EC
      3.5.4.21)--as a biosensitive element. In the work presented, we optimized this
      biosensor for creatinine analysis in real samples of dialysate in patients with
      renal failure. The optimized version of biosensor was applied for on-line
      monitoring of the level of creatinine in the patient's dialysate fluid in the
      course of dialysis session. High correlation between the biosensor analysis and
      traditional Jaffe method was demonstrated.

PMID- 22459583
TI  - A highly sensitive aptasensor towards Plasmodium lactate dehydrogenase for the
      diagnosis of malaria.
AB  - Finding a highly sensitive diagnostic technique for malaria has challenged
      scientists for the last century. In the present study, we identified versatile
      single-strand DNA aptamers for Plasmodium lactate dehydrogenase (pLDH), a
      biomarker for malaria, via the Systematic Evolution of Ligands by EXponential
      enrichment (SELEX). The pLDH aptamers selectively bound to the target proteins
      with high sensitivity (K(d)=16.8-49.6 nM). The selected aptamers were
      characterized using an electrophoretic mobility shift assay, a quartz crystal
      microbalance, a fluorescence assay, and circular dichroism spectroscopy. We also
      designed a simple aptasensor using electrochemical impedance spectroscopy; both
      Plasmodium vivax LDH and Plasmodium falciparum LDH were selectively detected with
      a detection limit of 1 pM. Furthermore, the pLDH aptasensor clearly distinguished
      between malaria-positive blood samples of two major species (P. vivax and P.
      falciparum) and a negative control, indicating that it may be a useful tool for
      the diagnosis, monitoring, and surveillance of malaria.

PMID- 22459584
TI  - Quantitative biomolecular sensing station based on magnetoresistive patterned
      arrays.
AB  - The combination of magnetoresistive sensors and magnetic labeling of bioanalytes,
      which are selectively captured by their complementary antibody in the proximity
      of the sensor is a powerful method in order to attain truly quantitative
      immunological assays. In this paper we present a technical solution to exploit
      the existing spin valve technology to readout magnetic signals of bio
      functionalized magnetic nanoparticles. The method is simple and reliable, and it
      is based on a discrete scan of lateral flow strips with a precise control of the
      contact force between sensor and sample. It is shown that the signal of the
      sensor is proportional to the local magnetization produced by the nanoparticles
      in a wide range of concentrations, and the sensitivity thresholds in both
      calibration samples and real immunorecognition assays of human chorionic
      gonadotropin hormone are well below the visual inspection limit (5.5 ng/ml).
      Furthermore the sample scanning approach and the reduced dimensions of the
      sensors provide unprecedented spatial resolution of the nanoparticle distribution
      across the supporting nitrocellulose strip, therefore enabling on-stick control
      references and multi-analyte capability.

PMID- 22459585
TI  - Functionalization of carbon buckypaper for the sensitive determination of
      hydrogen peroxide in human urine.
AB  - Here we report on a new approach for the electrochemical detection of hydrogen
      peroxide (H(2)O(2)) based on the co-immobilization of horseradish peroxidase and
      methylene blue on the functionalized carbon buckypaper supported by a titanium
      substrate. Cyclic voltammetry was used to study and optimize the performance of
      the resulting electrochemical biosensor. The proposed biosensor exhibited high
      analytical performance towards the quantification of H(2)O(2) at the
      physiological pH 7.4. Under optimized conditions, the biosensor shows a wide
      linear response range from 0.1 * 10(-6) to 5 * 10(-4)M concentrations of
      H(2)O(2). The detection limit was determined to be 7.5 * 10(-8)M (based on
      S/N=3). Reproducibility and stability of the fabricated biosensor were examined
      with satisfactory results. The biological relevance of the developed
      electrochemical biosensor has been further studied by the determination of
      H(2)O(2) in human urine samples of normal volunteers prior to and following the
      ingestion of coffee. Increased levels of urinary H(2)O(2) concentration suggest
      that oxidative stress is induced by coffee drinking in humans. There is
      considerable interest in oxidative stress as relates to human physiology. The
      sensitive determination of H(2)O(2) in human urine may serve as a valuable
      biomarker to effectively elucidate specific levels of oxidative stress in vivo.

PMID- 22459586
TI  - Investigation of DNA damage treated with perfluorooctane sulfonate (PFOS) on
      ZrO2/DDAB active nano-order film.
AB  - The interactions between DNA and small molecules with planar heterocyclic
      structure were indicated in previous researches. This study investigated the
      interactions between PFOS with linear chain structure and DNA. A new phenomenon
      of DNA damage due to PFOS using electrochemistry technique was proved. The data
      was obtained on a modified glassy carbon electrode, on which
      didodecyldimethylammonium bromide (DDAB), ZrO(2) and calf thymus DNA were
      immobilized layer-by-layer. Electrochemical response of DNA damage caused by PFOS
      was detected by differential pulse voltammetry (DPV) using methylene blue (MB) as
      electro-active indicator. The current of MB attenuated obviously after
      DNA/ZrO(2)/DDAB/GCE were incubated in PFOS. The shift of MB reduction peak
      potential indicates that PFOS is bound with DNA in groove probably by the first
      step of hydrophobic interaction and then the second step of intercalation into
      the base of DNA. X-ray photoelectron spectroscopic (XPS) was used to elucidate in
      detail the intercalation of PFOS into DNA and the formation of hydrogen bond
      between PFOS and DNA base. Electrochemical quartz crystal microbalance (EQCM)
      proved the formation of adducts of DNA and PFOS. Moreover, electrochemical
      impedance spectroscopy (EIS) indicates that the PFOS influence DNA structure and
      attenuate DNA charge transport. These results demonstrate that PFOS intercalated
      into DNA do induce DNA base damage.

PMID- 22459587
TI  - Oligopeptides functionalized surface plasmon resonance biosensors for detecting
      thiacloprid and imidacloprid.
AB  - By using phage display library, we identified two highly specific oligopeptide
      sequences RKRIRRMMPRPS and RNRHTHLRTRPR for binding neonicotinoids such as
      thiacloprid and imidacloprid. The former shows high affinity for thiacloprid
      whereas the latter shows high affinity for imidacloprid. Surprisingly, cross
      binding is minimal despite the similarity of the two molecules. To develop a
      neonicotinoid biosensor, these two oligopeptides are synthesized and immobilized
      on the surface of a surface plasmon resonance (SPR) chip with a bare-gold
      surface. This oligopeptide functionalized SPR biosensor can rapidly detect
      thiacloprid and imidacloprid in buffer solutions in a real-time manner. The limit
      of detection (LOD) for thiacloprid and imidacloprid is 1.2 MUM and 0.9 MUM,
      respectively.

PMID- 22459588
TI  - Type of shift work is a key factor on the association between personality traits
      and psychological health.

PMID- 22459589
TI  - Renal pelvis reduction during dismembered pyeloplasty: is it necessary?
AB  - OBJECTIVE: To compare treatment results in patients who underwent pyeloplasty
      with and without pelvic reduction for ureteropelvic junction obstruction (UPJO).
      METHODS: This randomized prospective study involved 40 patients, all diagnosed
      with unilateral UPJO; 20 each were randomly selected to undergo open dismembered
      pyeloplasty with pelvic reduction (group A) or pelvis-sparing pyeloplasty (group
      B). Patients were evaluated with ultrasound and DPTA renography scans 6 months
      postoperatively. Mean follow-up was 9 months. RESULTS: The mean age in group B
      was 5.71 +/- 6.36 years; in group A it was 4.81 +/- 6.78 years. There was a
      decrease in mean anteroposterior renal pelvic diameter (from 49.9 to 26.35 +/-
      0.949 mm in A and 50.9 to 30.8 +/- 1.556 mm in B) with improvement of split renal
      function (from 39 +/- 22.47% to 42.4 +/- 22.13% in A and 34.92 +/- 16.79% to 38.8
      +/- 19.66% in B), glomerular filtration rate (from 37.25 +/- 15.33 to 41.7 +/-
      19.34 ml/min in A and 31.3 +/- 18.50 to 38.1 +/- 23.23 ml/min in B) and draining
      curves on the 6-month scans, but without any significant difference between
      groups (p > 0.05). Two cases in group A and three in group B needed redo
      pyeloplasty, but without any significant difference in failure rate. CONCLUSION:
      Excision of the pelvis is not necessary in dismembered pyeloplasty procedures. We
      had similar surgical outcomes for patients with or without pelvis reduction.

PMID- 22459590
TI  - A false aneurysm.
AB  - OBJECTIVE: We report a case of a remaining hemi-thyroid following laryngectomy,
      which was misinterpreted as a pseudoaneurysm. METHODS: Case report and comment on
      this understandable error which is easily avoidable. RESULTS: A 59-year-old man
      had undergone salvage laryngectomy for recurrent squamous cell carcinoma of the
      larynx, which had previously been treated with radiotherapy. Three months after
      his laryngectomy, he presented with a sore neck and subcutaneous collections.
      Computed tomography revealed a unilateral mass with high signal contrast uptake
      anterior to the left common carotid artery, which was thought initially to be a
      carotid pseudoaneurysm. Further investigation, including ultrasonography and a
      review by the senior head and neck radiologist, demonstrated that this mass was
      actually the remnant hemi-thyroid preserved at laryngectomy (which is often
      misshapen compared with a normal hemi-thyroid). The collections were found to be
      recurrent tumour, and unnecessary further interventions were avoided. CONCLUSION:
      Ultrasonography easily distinguishes between a thyroid remnant and a
      pseudoaneurysm. Furthermore, the opinion of an experienced head and neck
      radiologist may be vital when interpreting complex post-surgical head and neck
      radiology.

PMID- 22459591
TI  - Impact of diabetes mellitus on outcomes in Japanese patients undergoing coronary
      artery bypass grafting.
AB  - BACKGROUND AND PURPOSE: There have been no large-scale studies on the impact of
      diabetes mellitus (DM) on outcomes in Japanese patients undergoing coronary
      artery bypass grafting (CABG). METHODS AND SUBJECTS: A multi-institutional
      retrospective cohort study was conducted in 14 Japanese centers. All adult
      patients who underwent isolated CABG from 2007 to 2008 were included (n=1522,
      mean age: 68.5years). The definitions of DM were all patients admitted with
      diagnosis of DM and preoperative glycated hemoglobin (Hb) A1c>=6.5%. Univariate
      and multivariate analyses were performed to identify the risk of morbidity and
      mortality. RESULTS: There were 849 DM and 572 non-DM patients. Preoperative mean
      HbA1c were 7.1% in the DM group and 5.7% in the non-DM group (p<0.0001).
      Preoperative, intraoperative, and 3-day average postoperative blood glucose (BG)
      were 146mg/dl, 172mg/dl, and 168mg/dl in the DM group, and 103mg/dl, 140mg/dl,
      and 136mg/dl in the non-DM group (all p<0.0001). Although there were no
      significant differences in postoperative cardiovascular events, the incidence of
      infection was significantly higher in the DM group than in the non-DM group (9.2%
      vs 6.1%, p=0.036) on the univariate analysis. The all-cause death was also
      relatively higher in the DM group than in the non-DM group (2.1% vs 1.1%,
      p=0.12), and this was likely related to infection. CONCLUSION: DM patients had
      worse perioperative BG control, higher incidence of infection, and higher
      mortality than non-DM patients. These results indicate that perioperative BG
      control guidelines should be standardized to obtain better surgical outcomes in
      Japanese DM patients.

PMID- 22459592
TI  - Risk factors associated with preterm delivery in women with cardiac disease.
AB  - BACKGROUND: The purpose of this study was to identify clinical characteristics of
      preterm delivery at less than 37 weeks of gestation (PD37G) and prenatal events
      associated with preterm delivery at less than 35 weeks of gestation (PD35G) in
      women with cardiac disease (WCD). METHODS: A case-control study was conducted of
      599 pregnancies in 479 single pregnant women with congenital or acquired cardiac
      lesions or cardiac arrhythmias. The relevant variables were compared between
      women who had PD35G (n=37) and the controls (n=562). Cardiac dysfunction was
      defined as the appearance of clinical symptoms of heart failure, abnormal
      electrocardiogram, or cardiac ultrasonography. RESULTS: PD37G occurred in 77
      cases (12.9%). The spontaneous and indicated preterm delivery was 26 (33.8%) and
      51 (66.2%) cases, respectively. The presence of cardiac dysfunction [odds ratio
      (OR) 21.82, 95% confidence interval (CI) 8.3-57.49], New York Heart Association
      class II (OR 3.96, 95% CI 1.05-14.93), cardiomyopathy (OR 7.74, 95% CI 1.69
      35.45) and pregnancy-induced hypertension (PIH) (OR 3.15, 95% CI 1.37-7.24) was
      significantly associated with an increased risk of PD35G. No maternal death was
      seen within one year after delivery. CONCLUSIONS: Although pregnancy and delivery
      are generally safe in WCD, it is necessary to be aware of the risk factors of
      cardiac dysfunction, cardiomyopathy, and PIH from the aspect of PD35G.

PMID- 22459593
TI  - The ticking time-bomb of asbestos: its insidious role in the development of
      malignant mesothelioma.
AB  - The relationship between asbestos exposure and malignant mesothelioma (MM) has
      been well established. Despite bans on asbestos use in an increasing number of
      nations, the prolonged latency from exposure to diagnosis, and the ongoing
      presence and use of these dangerous fibres, have led to the increasing prevalence
      of this deadly disease worldwide. Whilst occupational contact has been implicated
      in the bulk of diagnosed cases over the past 50 years, a significant proportion
      of disease has been linked to para-occupational, domestic and environmental
      exposure. In this review, we will provide an update on the impact of historical
      and ongoing asbestos contact in both occupational and non-occupational settings.
      Furthermore, we will address the unresolved controversies surrounding the use of
      chrysotile asbestos, the effect of gender and genetics on development of this
      disease, childhood mesothelioma and co-aetiological factors including SV40
      exposure.

PMID- 22459594
TI  - Magnetic resonance imaging identifies occult hip fractures missed by 64-slice
      computed tomography.
AB  - BACKGROUND: Citing the enhanced resolution of 64-slice computed tomography (CT),
      some clinicians now use CT instead of magnetic resonance imaging (MRI) to detect
      occult hip fracture. OBJECTIVE: Our objective was to determine the incidence of
      occult hip fractures missed by 64-slice CT but detected by MRI. METHODS: We
      reviewed the medical records and radiology reports of patients over age 60 years
      with a hip fracture (acetabular, intertrochanteric, trochanteric, femoral neck,
      and femoral head) during a 3-year period, January 1, 2007 through December 31,
      2009. We also reviewed all hip CT and MRI scans ordered during that period.
      Occult fractures were those visualized on CT or MRI but with negative plain
      films. We compared CT and MRI findings, and calculated percentages and 95%
      confidence intervals (CIs). RESULTS: Of 235 hip fractures, 211 were visible on
      initial plain films (90%, 95% CI 85-93%) and 24 (10%, 95% CI 6-15%) were occult.
      Eighteen occult fractures (7.6%, 95% CI 4.6-11.8%) were identified by CT (MRI not
      done), one (0.4%, 95% CI 0-2%) by MRI (CT not done), one (0.4%, 95% CI 0-2%) by
      both CT and MRI, and 4 patients (1.7%, 95% CI 0.5-4.3%) had a positive MRI but
      negative CT scan. CONCLUSION: Although 64-slice CT detected the majority of
      occult fractures, it missed four (2%) significant fractures detected by MRI. CT
      scan is helpful in the diagnosis of occult hip fracture, but one should not
      completely exclude the diagnosis based on a negative 64-slice CT scan in a
      patient with persistent, localized hip pain who cannot bear weight.

PMID- 22459595
TI  - Right flank pain: a case report of an interesting sonographic finding.
AB  - BACKGROUND: Focused bedside ultrasound is a screening tool frequently used by
      emergency physicians to evaluate hepatobiliary and renal pathology in patients
      presenting with abdominal complaints in the emergency department (ED). OBJECTIVE:
      This case report describes a sonographic finding that was interpreted as free
      fluid in the right upper quadrant. Computed tomography (CT) was used to confirm
      the diagnosis. CASE REPORT: A 44-year-old man presented to the ED with the sudden
      onset of right-sided abdominal pain and exhibited right costovertebral angle
      tenderness on physical examination. Focused bedside ultrasound of the right upper
      quadrant revealed severe hydronephrosis of the right kidney and free fluid of
      either subcapsular, perinephric, or peritoneal location represented by an
      anechoic stripe in Morison's pouch. On CT evaluation, this patient was found to
      have perinephric fluid accumulation from a presumed ruptured renal calyx in the
      setting of chronic ureteropelvic junction obstruction with severe hydronephrosis.
      CONCLUSION: The exact location of anechoic fluid in the abdomen is not always
      apparent on bedside ultrasound. To minimize misinterpreting focused bedside
      ultrasound examination findings, we recommend a number of sonographic techniques
      to identify possible mimics of free fluid. Suspected free fluid findings on
      bedside ultrasound should always be evaluated within the clinical context of the
      patient's presentation.

PMID- 22459596
TI  - Acute appendicitis presenting as acute gastritis in an adult patient with
      undiagnosed congenital gut malrotation: a case report.
AB  - BACKGROUND: We report a case of an atypical presentation of acute appendicitis in
      an adult due to an undiagnosed congenital gut malrotation. OBJECTIVE: The obvious
      benefit of observation with serial examinations followed by the use of computed
      tomography (CT) is discussed in aiding in the diagnosis for atypical
      presentations of appendicitis. CASE REPORT: A 45-year-old man who presented with
      epigastric pain and vomiting was diagnosed with acute left-sided appendicitis on
      CT scan. The patient's appendix was located in the left lower quadrant of the
      abdomen due to undiagnosed congenital gut malrotation, thus resulting in an
      atypical presentation of a common illness. CONCLUSION: Observation with serial
      examinations, followed by CT scanning if indicated, is an invaluable strategy to
      use in diagnosing atypical presentations of common pathology.

PMID- 22459597
TI  - Introduction of ultrasound into gross anatomy curriculum: perceptions of medical
      students.
AB  - BACKGROUND: The exposure to ultrasound technology during medical school education
      is highly variable across institutions. OBJECTIVES: The objectives of this study
      were to assess medical students' perceptions of ultrasound use to teach Gross
      Anatomy along with traditional teaching methods, and determine their ability to
      identify sonographic anatomy after focused didactic sessions. METHODS:
      Prospective observational study. Phase I of the study included three focused
      ultrasound didactic sessions integrated into Gross Anatomy curriculum. During
      Phase II, first-year medical students completed a questionnaire. RESULTS: One
      hundred nine subjects participated in this study; 96% (95% confidence interval
      [CI] 92-99%) agreed that ultrasound-based teaching increased students' knowledge
      of anatomy acquired through traditional teaching methods. Ninety-two percent (95%
      CI 87-97%) indicated that ultrasound-based teaching increases confidence to
      perform invasive procedures in the future. Ninety-one percent (95% CI 85-96%)
      believed that it is feasible to integrate ultrasound into the current Anatomy
      curriculum. Ninety-eight percent (95% CI 95-100%) of medical students accurately
      identified vascular structures on ultrasound images of normal anatomy of the
      neck. On a scale of 1 to 10, the average confidence level reported in
      interpreting the images was 7.4 (95% CI 7.1-7.7). Overall, 94% (95% CI 91-99%)
      accurately answered questions about ultrasound fundamentals and sonographic
      anatomy. CONCLUSIONS: The majority of medical students believed that it is
      feasible and beneficial to use ultrasound in conjunction with traditional
      teaching methods to teach Gross Anatomy. Medical students were very accurate in
      identifying sonographic vascular anatomy of the neck after brief didactic
      sessions.

PMID- 22459598
TI  - Screening for C9ORF72 repeat expansion in FTLD.
AB  - In the present study we aimed to determine the prevalence of C9ORF72 GGGGCC
      hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration
      (FTLD) patients and 174 neurologically normal controls. We identified the
      hexanucleotide repeat, in the pathogenic range, in 4 (2 bv-frontotemporal
      dementia (FTD) and 2 FTD-amyotrophic lateral sclerosis [ALS]) out of 53 patients
      and 1 neurologically normal control. Interestingly, 2 of the C9ORF72 expansion
      carriers also carried 2 novel missense mutations in GRN (Y294C) and in PSEN
      2(I146V). Further, 1 of the C9ORF72 expansion carriers, for whom pathology was
      available, showed amyloid plaques and tangles in addition to TAR (trans
      activation response) DNA-binding protein (TDP)-43 pathology. In summary, our
      findings suggest that the hexanucleotide expansion is probably associated with
      ALS, FTD, or FTD-ALS and occasional comorbid conditions such as Alzheimer's
      disease. These findings are novel and need to be cautiously interpreted and most
      importantly replicated in larger numbers of samples.

PMID- 22459599
TI  - Age-related frontoparietal changes during the control of bottom-up and top-down
      attention: an ERP study.
AB  - We investigated age-related changes in frontal and parietal scalp event-related
      potential (ERP) activity during bottom-up and top-down attention. Younger and
      older participants were presented with arrays constructed to induce either
      automatic "pop-out" (bottom-up) or effortful "search" (top-down) behavior.
      Reaction times (RTs) increased and accuracy decreased with age, with a greater
      age-related decline in accuracy for the search than for the pop-out condition.
      The latency of the P300 elicited by the visual search array was shorter in both
      conditions in the younger than in the older adults. Pop-out target detection was
      associated with greater activity at parietal than at prefrontal locations in
      younger participants and with a more equipotential prefrontal-parietal
      distribution in older adults. Search target detection was associated with greater
      activity at prefrontal than at parietal locations in older relative to younger
      participants. Thus, aging was associated with a more prefrontal P300 scalp
      distribution during the control of bottom-up and top-down attention. Early
      latency extrastriate potentials were enhanced and N2-posterior-contralateral
      (N2pc) was reduced in the older group, supporting the idea that the frontal
      enhancements may be due to a compensation for disinhibition and distraction in
      the older adults. Taken together these findings provide evidence that younger and
      older adults recruit different frontal-parietal networks during top-down and
      bottom-up attention, with older adults increasing their recruitment of a more
      frontally distributed network in both of these types of attention. This work is
      in accord with previous neuroimaging findings suggesting that older adults
      recruit more frontal activity in the service of a variety of tasks than younger
      adults.

PMID- 22459600
TI  - Berberine ameliorates beta-amyloid pathology, gliosis, and cognitive impairment
      in an Alzheimer's disease transgenic mouse model.
AB  - The accumulation of beta-amyloid (Abeta) peptide derived from abnormal processing
      of amyloid precursor protein (APP) is a common pathological hallmark of
      Alzheimer's disease (AD) brains. In this study, we evaluated the therapeutic
      effect of berberine (BBR) extracted from Coptis chinensis Franch, a Chinese
      medicinal herb, on the neuropathology and cognitive impairment in TgCRND8 mice, a
      well established transgenic mouse model of AD. Two-month-old TgCRND8 mice
      received a low (25 mg/kg per day) or a high dose of BBR (100 mg/kg per day) by
      oral gavage until 6 months old. BBR treatment significantly ameliorated learning
      deficits, long-term spatial memory retention, as well as plaque load compared
      with vehicle control treatment. In addition, enzyme-linked immunosorbent assay
      (ELISA) measurement showed that there was a profound reduction in levels of
      detergent-soluble and -insoluble beta-amyloid in brain homogenates of BBR-treated
      mice. Glycogen synthase kinase (GSK)3, a major kinase involved in APP and tau
      phosphorylation, was significantly inhibited by BBR treatment. We also found that
      BBR significantly decreased the levels of C-terminal fragments of APP and the
      hyperphosphorylation of APP and tau via the Akt/glycogen synthase kinase 3
      signaling pathway in N2a mouse neuroblastoma cells stably expressing human
      Swedish mutant APP695 (N2a-SwedAPP). Our results suggest that BBR provides
      neuroprotective effects in TgCRND8 mice through regulating APP processing and
      that further investigation of the BBR for therapeutic use in treating AD is
      warranted.

PMID- 22459601
TI  - Phospholipase A2: the key to reversing long-term memory impairment in a gastropod
      model of aging.
AB  - Memory failure associated with changes in neuronal circuit functions rather than
      cell death is a common feature of normal aging in diverse animal species. The
      (neuro)biological foundations of this phenomenon are not well understood although
      oxidative stress, particularly in the guise of lipid peroxidation, is suspected
      to play a key role. Using an invertebrate model system of age-associated memory
      impairment that supports direct correlation between behavioral deficits and
      changes in the underlying neural substrate, we show that inhibition of
      phospholipase A(2) (PLA(2)) abolishes both long-term memory (LTM) and neural
      defects observed in senescent subjects and subjects exposed to experimental
      oxidative stress. Using a combination of behavioral assessments and
      electrophysiological techniques, we provide evidence for a close link between
      lipid peroxidation, provocation of phospholipase A(2)-dependent free fatty acid
      release, decline of neuronal excitability, and age-related long-term memory
      impairments. This supports the view that these processes suspend rather than
      irreversibly extinguish the aging nervous system's intrinsic capacity for
      plasticity.

PMID- 22459603
TI  - Innominate 3D motion modeling: biomechanically interesting, but clinically
      irrelevant.

PMID- 22459602
TI  - Mutant FUS induces endoplasmic reticulum stress in amyotrophic lateral sclerosis
      and interacts with protein disulfide-isomerase.
AB  - Mutations in the gene encoding fused in sarcoma (FUS) are linked to amyotrophic
      lateral sclerosis (ALS), but the mechanisms by which these mutants trigger
      neurodegeneration remain unknown. Endoplasmic reticulum (ER) stress is
      increasingly recognized as an important and early pathway to motor neuron death
      in ALS. FUS is normally located in the nucleus but in ALS, FUS redistributes to
      the cytoplasm and forms inclusions. In this study, we investigated whether FUS
      induces ER stress in a motor neuron like cell line (NSC-34). We demonstrate that
      ER stress is triggered in cells expressing mutant FUS, and this is closely
      associated with redistribution of mutant FUS to the cytoplasm. Mutant FUS also
      colocalized with protein disulfide-isomerase (PDI), an important ER chaperone, in
      NSC-34 cells and PDI was colocalized with FUS inclusions in human ALS lumbar
      spinal cords, in both sporadic ALS and mutant FUS-linked familial ALS tissues.
      These findings implicate ER stress in the pathophysiology of FUS, and provide
      evidence for common pathogenic pathways in ALS linked to the ER.

PMID- 22459604
TI  - Effectiveness of proprioceptive exercises for ankle ligament injury in adults: a
      systematic literature and meta-analysis.
AB  - The purpose of this study was to assess the effectiveness of such proprioceptive
      exercise following ankle ligament injury. A systematic review of the databases
      MEDLINE, EMBASE, CINHAL, AMED, the Cochrane library database and the PEDro
      database, in addition to unpublished literature databases was conducted to July
      2011. When appropriate, meta-analysis was conducted to pool results from
      homogeneous studies. The methodological quality of the literature was reviewed
      using the Critical Appraisal Skills Programme tool. The results indicated that
      there is no statistically significant difference in recurrent injury between the
      addition of proprioceptive exercises during the rehabilitation of patients
      following ankle ligament injury (p = 0.68). The addition of proprioceptive
      training demonstrated a significant reduction in subjective instability and
      functional outcomes (p < 0.05). There was no consensus on the advantages of
      including proprioceptive training in the rehabilitation of this population for
      swelling, postural sway, joint position sense, ankle range of motion or return to
      sport outcomes. Further study is warranted to develop the rigour of the evidence
      base and to determine the optimal proprioceptive training programme following
      ankle ligament injury with different populations.

PMID- 22459605
TI  - Time series geophysical monitoring of permanganate injections and in situ
      chemical oxidation of PCE, OU1 area, Savage Superfund Site, Milford, NH, USA.
AB  - In situ chemical oxidation (ISCO) treatment with sodium permanganate, an
      electrically conductive oxidant, provides a strong electrical signal for tracking
      of injectate transport using time series geophysical surveys including direct
      current (DC) resistivity and electromagnetic (EM) methods. Effective remediation
      is dependent upon placing the oxidant in close contact with the contaminated
      aquifer. Therefore, monitoring tools that provide enhanced tracking capability of
      the injectate offer considerable benefit to guide subsequent ISCO injections.
      Time-series geophysical surveys were performed at a superfund site in New
      Hampshire, USA over a one-year period to identify temporal changes in the bulk
      electrical conductivity of a tetrachloroethylene (PCE; also called
      tetrachloroethene) contaminated, glacially deposited aquifer due to the injection
      of sodium permanganate. The ISCO treatment involved a series of pulse injections
      of sodium permanganate from multiple injection wells within a contained area of
      the aquifer. After the initial injection, the permanganate was allowed to
      disperse under ambient groundwater velocities. Time series geophysical surveys
      identified the downward sinking and pooling of the sodium permanganate atop of
      the underlying till or bedrock surface caused by density-driven flow, and the
      limited horizontal spread of the sodium permanganate in the shallow parts of the
      aquifer during this injection period. When coupled with conventional monitoring,
      the surveys allowed for an assessment of ISCO treatment effectiveness in
      targeting the PCE plume and helped target areas for subsequent treatment.

PMID- 22459606
TI  - Synthetic cathinones: chemistry, pharmacology and toxicology of a new class of
      designer drugs of abuse marketed as "bath salts" or "plant food".
AB  - In 2000s, many synthetic cathinones have received a renewed popularity as
      designer drugs of abuse, particularly among young people. Despite being marketed
      as "bath salts" or "plant food" and labeled "not for human consumption", people
      utilize these substances for their amphetamine or cocaine like effects. Since the
      time of their appearance in the recreational drug market, in several countries
      have been signaled numerous confirmed cases of abuse, dependence, severe
      intoxication and deaths related to the consumption of synthetic cathinones. The
      aim of this paper is to summarize the clinical, pharmacological and toxicological
      information about this new class of designer drugs of abuse.

PMID- 22459607
TI  - Effects of acrylamide exposure on serum hormones, gene expression, cell
      proliferation, and histopathology in male reproductive tissues of Fischer 344
      rats.
AB  - Acrylamide (AA) is a reactive monomer used in many technological applications,
      but it is the incidental formation during cooking of common starchy foods that
      leads to pervasive human exposure, typically in the range of 1 MUg/kg body weight
      (bw)/day (d). AA is carcinogenic in multiple organs from both sexes of several
      rodent models and a consistent body of evidence points to a genotoxic mechanism
      based on metabolism to a DNA-reactive epoxide, glycidamide (GA). In F344 rats,
      tumorigenesis occurs in several hormonally regulated tissues (thyroid, mammary
      gland, and peri-testicular mesothelium), which has prompted speculation about
      endocrine dysregulation as a possible mechanism. The present study evaluated the
      effects of a 14 d exposure to AA administered through the drinking water on
      reproductive tissues and the hypothalamic-pituitary-testes (HPG) axis in male
      F344 rats. The doses selected encompass a range from approximately 2.5 mg/kg
      bw/d, which is carcinogenic after lifetime exposure, to 50 mg/kg bw/d, a
      maximally tolerable dose that causes hind limb paralysis. AA caused significant
      changes in serum hormones, histopathology, testicular gene expression, and cell
      proliferation, especially at the highest dose. Despite strong evidence for
      activation of the HPG axis subsequent to decreases in testosterone levels, and
      histopathological changes associated with significant effects on Leydig and germ
      cells, with concomitant mRNA expression changes, the precise mechanism(s) for AA
      induced testicular toxicity remains unclear; however, the absence of evidence for
      increased proliferation of the peri-testicular mesothelium (Ki-67
      immunoreactivity) does not support hormonal dysregulation as a contributing
      factor to the predisposition of this tissue to the carcinogenic effects of AA.

PMID- 22459608
TI  - [22Q11 microdeletion syndrome: cardiorespiratory symptoms and fibrobronchoscopy].
AB  - The 22q11 deletion syndrome is a frequent contiguous-gene deletion syndrome. This
      disorder has a broad spectrum of phenotypic manifestations. It includes various
      syndromes such as DiGeorge syndrome. The most frequent clinical manifestations
      are congenital cardiac defects, characteristic facies, palate malformations,
      hypoparathyroidism, immunodeficiency due to thymic hypoplasia, growth
      retardation, and behavioural and psychiatric problems. Among the symptoms
      observed, many patients suffer from respiratory insufficiency or failure. The
      origin is often multifactorial. Structural airway abnormalities are frequently
      found in this syndrome. In many of these patients the malformation is mild or non
      existent, and remains asymptomatic. However, in some cases it can cause a severe
      respiratory insufficiency, being diagnosed when other disorders are ruled out.
      These cases illustrate the importance of early visualisation of the airway by
      fibrobronchoscopy in the management of the patient with 22q11 deletion syndrome
      who has recurrent respiratory difficulties.

PMID- 22459609
TI  - [Cisplatin induced reversible posterior leukoencephalopathy].

PMID- 22459613
TI  - Engineering commensal bacteria for prophylaxis against infection.
AB  - Infectious diseases are the leading causes of death worldwide. The development of
      efficient and low cost prophylactics to prevent pathogenic infection is given
      high priority in the twenty-first century. Commensal bacteria are largely seen as
      harmless and can survive symbiotically (in many cases) in niches throughout the
      human body. Advances in genetic engineering and understanding of pathogenesis
      have revealed many potential strategies to develop engineered bacteria for
      prophylaxis purposes: including live vaccines and anti-infective agents. In this
      review, we discuss recent advances and potentialities of prophylaxis with
      engineered bacteria.

PMID- 22459614
TI  - A cross-over study of the acute effects of espresso coffee on glucose tolerance
      and insulin sensitivity in people with type 2 diabetes mellitus.
AB  - The objective was to determine the effect of a single dose of espresso
      caffeinated coffee, decaffeinated coffee, or water on glucose tolerance and
      insulin sensitivity in people with type 2 diabetes mellitus. Eighteen
      participants who were habitual coffee drinkers, were studied using a random-order
      cross-over design. After a fasting blood sample participants consumed either a
      double-shot black espresso coffee, decaffeinated coffee, or hot water. The main
      outcomes were area under the curve (AUC) glucose and insulin, and insulin
      sensitivity (Matsuda index) during a 75 g oral glucose tolerance test (OGTT)
      performed one hour later. Other outcomes were change in glucose and insulin and
      also the insulinogenic index (IGI) and disposition index (DI). AUC glucose was
      marginally different between beverages (P=.06) being greater following
      caffeinated coffee than water, mean difference 104 mmol/L/180 min (95% CI 0.1 to
      198.1, P=.031), or decaffeinated coffee, mean difference 92.1 mmol/L/180 min (95%
      CI -1.9 to 186.1, P=.055). There was no difference in AUC insulin (P=.87) or
      insulin sensitivity (P=.47), nor in change in glucose or insulin over the hour
      following beverage consumption. There was a marginal difference in IGI between
      beverages (P=.097) with coffee having a lower incremental increase in
      insulin/glucose than water (P=.037) though no difference between coffee and
      decaffeinated coffee (P=.54) and no difference in DI (P=.23). Black espresso
      coffee in people with type 2 diabetes mellitus results in a marginally greater
      excursion of glucose during a following OGTT compared with water or decaffeinated
      coffee. This effect does not appear to be mediated by changes in insulin
      sensitivity.

PMID- 22459615
TI  - CYP1B1 Asn453Ser polymorphism and colorectal cancer risk: a meta-analysis.
AB  - Studies investigating the association between cytochrome P450 1B1 (CYP1B1)
      Asn453Ser (453 A/G, rs1800440) polymorphism and colorectal cancer (CRC) risk
      report conflicting results. The aim of this study was to quantitatively summarize
      the evidence for such a relationship. Two investigators independently searched
      the Medline and Embase Databases. Summary odds ratios (ORs) and 95% confidence
      intervals (95% CIs) for CYP1B1 polymorphism and CRC were calculated in a fixed
      effects model (the Mantel-Haenszel method) and a random-effects model (the
      DerSimonian and Laird method) when appropriate. The pooled ORs were performed for
      co-dominant model (GG vs AA, GA vs AA), dominant model (GG+GA vs AA), and
      recessive model (GG vs GA+AA). This meta-analysis included 7 case-control
      studies, which included 6375 CRC cases and 7003 controls. Overall, the variant
      genotypes (GG and GA) of the 453 A/G were not associated with CRC risk when
      compared with the wild-type AA homozygote (GG vs AA, OR=0.94, 95% CI=0.77-1.14;
      GA vs AA, OR=0.99, 95% CI=0.87-1.12). Similarly, no associations were found in
      the dominant and recessive models (dominant model, OR=0.98, 95% CI=0.87-1.09;
      recessive model, OR=0.94, 95% CI=0.77-1.14). When stratifying for country, study
      sample size, matched control and source of controls, no evidence of significant
      association was observed in any subgroup, except among those studies from
      "Canada". No publication bias was found in the present study. No association was
      found between the CYP1B1 Asn453Ser polymorphism and risk of CRC among Caucasians.

PMID- 22459616
TI  - The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral,
      selective androgen receptor modulator, in healthy young men.
AB  - BACKGROUND: Concerns about potential adverse effects of testosterone on prostate
      have motivated the development of selective androgen receptor modulators that
      display tissue-selective activation of androgenic signaling. LGD-4033, a novel
      nonsteroidal, oral selective androgen receptor modulator, binds androgen receptor
      with high affinity and selectivity.  Objectives. To evaluate the safety,
      tolerability, pharmacokinetics, and effects of ascending doses of LGD-4033
      administered daily for 21 days on lean body mass, muscle strength, stair-climbing
      power, and sex hormones. METHODS: In this placebo-controlled study, 76 healthy
      men (21-50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033
      daily for 21 days. Blood counts, chemistries, lipids, prostate-specific antigen,
      electrocardiogram, hormones, lean and fat mass, and muscle strength were measured
      during and for 5 weeks after intervention. RESULTS: LGD-4033 was well tolerated.
      There were no drug-related serious adverse events. Frequency of adverse events
      was similar between active and placebo groups. Hemoglobin, prostate-specific
      antigen, aspartate aminotransferase, alanine aminotransferase, or QT intervals
      did not change significantly at any dose. LGD-4033 had a long elimination half
      life and dose-proportional accumulation upon multiple dosing. LGD-4033
      administration was associated with dose-dependent suppression of total
      testosterone, sex hormone-binding globulin, high density lipoprotein cholesterol,
      and triglyceride levels. follicle-stimulating hormone and free testosterone
      showed significant suppression at 1.0-mg dose only. Lean body mass increased dose
      dependently, but fat mass did not change significantly. Hormone levels and lipids
      returned to baseline after treatment discontinuation. CONCLUSIONS: LGD-4033 was
      safe, had favorable pharmacokinetic profile, and increased lean body mass even
      during this short period without change in prostate-specific antigen. Longer
      randomized trials should evaluate its efficacy in improving physical function and
      health outcomes in select populations.

PMID- 22459617
TI  - Genes against aging.
AB  - Individual mutations in mice can slow aging: They extend life span by retarding a
      wide range of harmful, age-dependent changes in multiple cells and tissues.
      Evolutionary changes-by definition, changes in DNA sequence-can lead to even more
      dramatic postponement of age-dependent deterioration. Genetic variation within a
      species, for example among breeds of dogs, can also lead to major changes in
      aging rate, although there is not yet any strong evidence for similar genetic
      variation that modulates aging in rodents or humans. This essay compares
      different strategies for using genetic information to clarify questions in
      biogerontology, suggesting an emphasis on genes that can retard multiple forms of
      age-dependent dysfunction in parallel.

PMID- 22459619
TI  - Contribution of frailty markers in explaining differences among individuals in
      five samples of older persons.
AB  - BACKGROUND: There has been little research on the relative importance of frailty
      markers. The objective was to investigate the association among seven frailty
      domains (nutrition, physical activity, mobility, strength, energy, cognition, and
      mood) and their relative contribution in explaining differences among individuals
      in five samples of older persons. METHODS: Data from five studies of aging were
      analyzed using multiple correspondence analysis. Aggregation of frailty markers
      was evaluated using graphical output. Decomposition of variability was used to
      assess the relative contribution of each marker in each sample. Results were
      combined across the samples to assess the average contribution. RESULTS: Frailty
      markers were found to consistently aggregate in each sample, suggesting a
      possible underlying construct. Physical strength had the highest contribution on
      average in explaining differences among individuals. Mobility and energy also had
      large contributions. Nutrition and cognition had the smallest contributions.
      CONCLUSIONS: Our results provide further evidence supporting the notion that
      frailty domains may belong to a common construct. Physical strength may be the
      most important discriminating characteristic.

PMID- 22459618
TI  - FOXO3 gene variants and human aging: coding variants may not be key players.
AB  - FOXO3 is generally recognized as a "master" gene in aging since its association
      with longevity has been replicated in multiple organisms and human populations. A
      group of single nucleotide polymorphisms in linkage disequilibrium with a coding
      region has been associated with human longevity, but the actual functional
      variant is unidentified. Therefore, we sequenced the coding region in our long
      lived Japanese American population in order to enhance resources for fine mapping
      this region. We demonstrate that of 38 published variants, 6 are misalignments
      with homologous nonallelic sequences from FOXO3B (ZNF286B), a pseudogene on a
      different chromosome; 2 are attributable to ZNF286B only, and the remaining 30
      were unconfirmed, indicating that they are very rare and not likely involved in
      longevity. Furthermore, we identified a novel, unique, nonsynonymous coding
      variant in exon 3 (Gly566Ala; rs138174682) that is prevalent in multiple ethnic
      groups but appeared too rare for major longevity effects in our study
      populations.

PMID- 22459621
TI  - The effect of stability and change in health behaviors on trajectories of body
      mass index in older Americans: a 14-year longitudinal study.
AB  - BACKGROUND: Obesity is increasingly prevalent among older adults, yet little is
      known about the impact of health behaviors on the trajectories of body weight in
      this age group. METHODS: We examined the effect of time-varying smoking, physical
      activity (PA), alcohol use, and changes thereof, on the 14-year (1992-2006)
      trajectory of body- mass index (BMI) in a cohort of 10,314 older adults from the
      Health and Retirements Study, aged 51-61 years at baseline. Hierarchical linear
      modeling (HLM) quantifies the effect of smoking, PA, and alcohol use (user
      status, initiation and cessation) on intercept and rate-of-change in BMI
      trajectory, and tests for variations in the strength of association between each
      behavior and BMI. RESULTS: Over 14 years (82,512 observations), BMI increased
      approximated by a quadratic function. Smoking and PA (user status and initiation)
      were associated with significantly lower BMI trajectories over time. Cessation of
      smoking and PA resulted in higher BMI trajectories over time. The weight-gaining
      effect of smoking cessation increased, while the strength of association between
      BMI trajectories and PA or alcohol use were constant over time. Socio-economic
      and health status differences explained the effects of alcohol use on BMI
      trajectory. CONCLUSIONS: In older adults, smoking and PA, and changes thereof,
      vary in their long-term effect on trajectories of BMI. Barring increases in PA
      levels, older smokers who quit today are expected to gain significantly more
      weight than two decades ago. This knowledge is essential for the design of
      smoking cessation, physical activityPA, and weight-control interventions in older
      adults.

PMID- 22459622
TI  - Review: quantifying mitochondrial dysfunction in complex diseases of aging.
AB  - There is accumulating evidence that mitochondrial respiratory malfunction is
      associated with aging-associated complex diseases. However, progress in our
      understanding of these diseases has been hampered by the sensitivity and
      throughput of systems employed to quantify dysfunction and inherent limitations
      of the biological systems studied. In this review, we describe and contrast two
      methodologies that have been developed for measuring mitochondrial function to
      address the need for improved sensitivity and increased throughput. We then
      consider the utility of each methodology in studying three biological systems:
      isolated mitochondria, cultured cells, and cell fibers and tissues. Finally, we
      discuss the application of each methodology in the study of mitochondrial
      dysfunction in Alzheimer's disease, type 2 diabetes mellitus, and aging
      associated autophagy impairment and mitochondrial malfunction. We conclude that
      the methodologies are complementary, and researchers may need to examine multiple
      biological systems to unravel complex diseases of aging.

PMID- 22459620
TI  - Energy balance changes the anabolic effect of postexercise feeding in older
      individuals.
AB  - We previously showed that consumption of protein immediately after exercise in
      older adults enhances nitrogen balance when energy balance (EB) is maintained.
      Because daily EB routinely varies, it is important to know whether benefits of
      postexercise protein consumption also occur with changing EB. Within an
      experiment, participants consumed an isonitrogenous-isocaloric diet with the
      timing of a protein (PRO + CHO) or carbohydrate (CHO) beverage immediately after
      exercise versus earlier in the day. Within hypocaloric and hypercaloric cohorts,
      3-day mean nitrogen balance was not different when protein was consumed
      immediately after exercise, although there was a trend (p = .09) for higher
      nitrogen balance in the positive EB. However, when data from our three studies
      were combined, the anabolic effect of postexercise feeding was evident during
      positive EB but not negative EB. EB is therefore an important consideration in
      the postexercise anabolic effect of protein feeding.

PMID- 22459623
TI  - Economic evaluation of sequential treatments for follicular non-hodgkin lymphoma.
AB  - BACKGROUND: The cost-effectiveness analyses of follicular lymphoma (FL)
      treatments have focused on the second-line rituximab maintenance in patients with
      relapsed FL. The assessment of full FL treatment chain has been lacking.
      OBJECTIVE: The aim of this study was to assess the cost-effectiveness of FL
      treatment sequences. METHODS: Transitions between progression-free first-line
      treatment (PF1), progression-free second-line treatment (PF2), progression, and
      death health states were simulated with a probabilistic Markov model with half
      cycle correction. At first, patients were assumed to be receiving rituximab with
      cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) induction. The
      first-line RCHOP induction responders continued without (RCHOP) or with (RCHOPR)
      the first-line rituximab-maintenance treatment. In the case of PF1 failure,
      patients received RCOPR/bendamustine or RCOPR/COP according to the European
      Society for Medical Oncology guidance. In the case of PF2 failure, patients were
      expected to receive the best supportive care (BSC). The survivals and adverse
      events were estimated with direct and indirect comparisons. Health outcomes and
      Finnish payer (drug, drug administration, monitoring, test, progression, serious
      adverse event) costs valued in 2010 euros were discounted with 3% per annum.
      RESULTS: The mean discounted lifetime overall survival with FL was 9.6 to 11.5
      years, quality-adjusted survival was 7.2 to 8.8 quality-adjusted life-years
      (QALYs), progression-free time was 7.7 to 10.2 years, and costs were ?153,425 to
      ?168,549, depending on the treatment sequence. The incremental cost-effectiveness
      ratios for RCHOPR->RCOPR/bendamustine->BSC, RCHOPR->RCOPR/COP->BSC, and RCHOP
      >RCOPR/bendamustine->BSC were ?9575/?8014/?5900, ?9881/?8310/?6013, and
      ?8812/?7194/?5808, respectively, per QALY/life-year/progression-free year gained
      in comparison with RCHOP->RCOPR/COP->BSC. According to the cost-effectiveness
      acceptability frontier, the treatment of 61.8% to 72.7% patients with RCHOPR
      >RCOPR/bendamustine->BSC was cost effective at ?20,000 to ?30,000/QALY gained
      (expected value of perfect information [EVPI], ?1287 to ?1976/patient). The
      relative results were found to be robust in sensitivity analyses, and, in the
      direct comparison that included only head-to-head data, the first-line rituximab
      maintenance had 93.1% cost-effectiveness probability at ?20,000/QALY gained
      (EVPI, ?282/patient). CONCLUSION: Sequences that included first-line rituximab
      maintenance is and second-line bendamustine are potentially cost effective in the
      treatment of FL. LIMITATIONS: Because of data available, health outcomes of the
      first-line rituximab induction were excluded, the second-line patients on COP
      were assumed to incur the cost of COP, and the efficacy and adverse events of
      CHOP and the efficacy and adverse events of bendamustine were estimated
      indirectly according to a comparison of rituximab+bendamustine and RCHOP, and
      treatment benefits were truncated.

PMID- 22459624
TI  - Modifications in erythrocyte membrane zeta potential by Plasmodium falciparum
      infection.
AB  - The zeta potential (ZP) is an electrochemical property of cell surfaces that is
      determined by the net electrical charge of molecules exposed at the surface of
      cell membranes. Membrane proteins contribute to the total net electrical charge
      of cell surfaces and can alter ZP through variation in their copy number and
      changes in their intermolecular interactions. Plasmodium falciparum extensively
      remodels its host red blood cell (RBC) membrane by placing 'knob'-like structures
      at the cell surface. Using an electrophoretic mobility assay, we found that the
      mean ZP of human RBCs was -15.7 mV. In RBCs infected with P. falciparum
      trophozoites ('iRBCs'), the mean ZP was significantly lower (-14.6 mV, p<0.001).
      Removal of sialic acid from the cell surface by neuraminidase treatment
      significantly decreased the ZP of both RBCs (-6.06 mV) and iRBCs (-4.64 mV).
      Parasite-induced changes in ZP varied by P. falciparum clone and the presence of
      knobs on the iRBC surface. Variations in ZP values were accompanied by altered
      binding of iRBCs to human microvascular endothelial cells (MVECs). These data
      suggest that parasite-derived knob proteins contribute to the ZP of iRBCs, and
      that electrostatic and hydrophobic interactions between iRBC and MVEC membranes
      are involved in cytoadherence.

PMID- 22459625
TI  - Lysine catabolism in Haemonchus contortus and Teladorsagia circumcincta.
AB  - Catabolism of lysine through the pipecolate, saccharopine and cadaverine pathways
      has been investigated in L3 and adult Haemonchus contortus and Teladorsagia
      circumcincta. Both enzymes of the saccharopine pathway (lysine ketoglutarate
      reductase (LKR) and saccharopine dehydrogenase (SDH)) were active in L3 and adult
      worms of both species. All three enzymes which catabolise lysine to alpha-amino
      adipic semialdehyde via pipecolate (lysine oxidase (LO), Delta(1)-piperideine-2
      carboxylate reductase (Pip2CR) and pipecolate oxidase (PipO)) were present in
      adult worms, whereas the pathway was incomplete in L3 of both species; Pip2CR
      activity was not detected in the L3 of either parasite species. In adult worms,
      the saccharopine pathway would probably be favoured over the pipecolate pathway
      as the K(m) for lysine was lower for LKR than for LO. Neither lysine
      dehydrogenase nor lysine decarboxylase activity was detected in the two parasite
      species. Enzyme activities and substrate affinities were higher for all five
      enzymes in adult worms than in L3. An unexpected finding was that both LKR and
      SDH were dual co-factor enzymes and not specific for either NAD(+) or NADP(+), as
      is the case in other organisms. This novel property of LKR/SDH suggests it could
      be a good candidate for anthelmintic targeting.

PMID- 22459626
TI  - Toxicity of solvents and surfactants to Amblyomma cajennense (Fabricius, 1787)
      (Acari: Ixodidae) and Dermacentor nitens (Neumann, 1897) (Acari: Ixodidae)
      larvae.
AB  - The objective of this work was to verify the sensitivity of Amblyomma cajennense
      and Dermacentor nitens larvae to the solvents ethanol, methanol, acetone, xylol
      and dimethyl sulfoxide (DMSO) and the surfactant Tween 80. The first four
      solvents were tested at analytical purity while the DMSO and surfactant Tween 80
      were tested at a concentration of 1%. The substances tested at analytical purity
      that caused high mortality were also tested at concentrations of 50%, 25% and 1%.
      The larval packet test was used, with 10 repetitions for each treatment. A
      control group was also formed with the same number of repetitions, in which the
      larvae were only exposed to distilled water. In the first experiment, only xylol
      was highly toxic at the concentrations tested, causing mortality above 90% for
      larvae of both species. In the second experiment, xylol at 1% and at 25% showed
      low toxicity to the A. cajennense and D. nitens larvae, respectively, since the
      percentage mortality was statistically similar to that of the control group
      (p>0.05).

PMID- 22459627
TI  - Comment on, "Is there a place for corifollitropin alfa in IVF/ICSI cycles? A
      systematic review and meta-analysis".

PMID- 22459630
TI  - Quantification of mitochondrial abundance.

PMID- 22459628
TI  - A comparison of live birth rates and cumulative ongoing pregnancy rates between
      Europe and North America after ovarian stimulation with corifollitropin alfa or
      recombinant follicle-stimulating hormone.
AB  - OBJECTIVE: To compare live birth rates after fresh embryo transfer (ET) and
      cumulative ongoing pregnancy rates after fresh ET and frozen-thawed (ET) between
      continents and overall after one treatment cycle with corifollitropin alfa or
      recombinant FSH. DESIGN: Double-blind, multicenter, randomized controlled trial.
      SETTING: Fourteen centers in North America (NA); 20 in Europe (EU). PATIENT(S):
      804 NA patients and 702 EU patients. INTERVENTION(S): Patients >60 kg received a
      single dose of corifollitropin alfa or daily rFSH for the first 7 days of
      controlled ovarian stimulation. MAIN OUTCOME MEASURE(S): Live birth rates.
      RESULT(S): Within each continent no differences were noted between the two
      treatment groups; however, between continents, the cumulative ongoing pregnancy
      rate and live birth rate were considerably higher in NA than in EU. The live
      birth rate in NA was 39.2% in both treatment groups compared with 31.5% and 28.8%
      in EU after corifollitropin alfa and rFSH treatment, respectively. Considering
      the number of embryos transferred, the live birth rate per ET was still higher in
      NA than in EU (42.7% v.s 36.8% with corifollitropin alfa and 41.6% vs. 30.9% with
      rFSH). Overall live birth rates after fresh ET were 35.6% and 34.4% (estimated
      difference 1.1% [95% confidence interval -3.7-5.8]), and the estimated cumulative
      live birth rates were 43.4% and 41.3% with corifollitropin alfa and rFSH,
      respectively. CONCLUSION(S): Live birth rates and cumulative pregnancy rates were
      higher in NA than in EU after treatment with either corifollitropin alfa or daily
      rFSH; both treatment protocols provided equal success rates. CLINICALTRIALS.GOV
      IDENTIFIERS: NCT00703014 and NCT00702273.

PMID- 22459631
TI  - Comparison of warm and cold contrast media for hysterosalpingography: a
      prospective, randomized study.
AB  - OBJECTIVE: To compare the use of warm medium and cold medium for alleviating pain
      and side effects during hysterosalpingography (HSG). DESIGN: Prospective
      randomized study. SETTING: University hospital. PATIENT(S): Two hundred infertile
      women who needed HSG were recruited from January 2010 to June 2011. The exclusion
      criteria were acute low reproductive duct infection, known hypersensitivity to
      iodine, genital bleeding, or malignancy. INTERVENTION(S): Subjects were
      randomized to undergo HSG using a medium prewarmed to 37 degrees C or a medium at
      room temperature. MAIN OUTCOME MEASURE(S): Incidence of vasovagal episodes and
      visual analog scale (VAS) pain scores during HSG. RESULT(S): Patients' VAS pain
      scores during HSG were significantly lower in the warm media group initially but
      showed no statistical difference at 30 minutes after injection. Medium
      temperature showed a linear association with VAS score. The total number of
      vasovagal episodes was higher in the cold medium group. CONCLUSION(S): Warm
      contrast medium alleviates the pain associated with HSG and decreases the
      incidence of vasovagal episodes during HSG. CLINICAL TRIALS REGISTRATION NUMBER:
      NCT01339338.

PMID- 22459633
TI  - What is the optimal follicular size before triggering ovulation in intrauterine
      insemination cycles with clomiphene citrate or letrozole? An analysis of 988
      cycles.
AB  - OBJECTIVE: To determine the optimal size of the leading follicle before human
      chorionic gonadotropin (hCG) administration in cycles with clomiphene citrate
      (CC) and letrozole, and to examine any differences in the optimal leading
      follicle size between cycles with CC and letrozole. DESIGN: A retrospective
      study. SETTING: University hospital-based reproductive center. PATIENT(S): 1,075
      women undergoing intrauterine insemination cycles with CC or letrozole.
      INTERVENTION(S): Leading follicle diameters and endometrial thickness were
      recorded 24 hours before hCG administration, together with other cycles
      parameters, and were compared between pregnant and nonpregnant patients. MAIN
      OUTCOME MEASURE(S): Leading follicle diameter and intrauterine insemination
      outcome. RESULT(S): Eight percent of patients (n = 87) were excluded because
      their leading follicle was less than 18 mm by days 11 to 13. Pregnancy was
      recorded as clinical pregnancy with fetal heart activity seen at 6- to 7-week
      transvaginal ultrasound. For both CC and letrozole, higher pregnancy rates were
      achieved when the leading follicles were in the 23 to 28 mm range. The optimal
      size of the leading follicle was not statistically significantly different
      between cycles using CC or letrozole. However, for each endometrial thickness,
      the optimal follicular size of the leading follicle was different. Each
      additional millimeter of endometrial thickness increased the optimal follicular
      size by 0.5 mm. Thicker endometrial lining led to a higher probability of
      pregnancy. CONCLUSION(S): The optimal size of the leading follicle in ovulation
      induction with CC and letrozole is similar for both drugs and is closely related
      to the endometrial thickness.

PMID- 22459634
TI  - Insulin-like growth factor binding protein-2 and neurotrophin 3 synergize
      together to promote the expansion of hematopoietic cells ex vivo.
AB  - Co-culture of Umbilical Cord Blood (UCB) CD34+ cells with irradiated Mesenchymal
      Stem Cells (MSCs) without contact increase the expansion of Hematopoietic
      Progenitor Cells (HPC). Neurotrophin-3 (NT-3) and insulin-like growth factor
      binding protein-2 (IGFBP-2) are two factors whose expressions were significantly
      elevated in conditioned media derived from irradiated MSCs. To determine whether
      these factors are partly responsible for the growth promoting potential of MSCs,
      we investigated their impact on the growth and differentiation of UCB-CD34+
      cells. Addition of either factor alone had little impact on cell growth, however
      both factors synergized together to increase the expansion of total nucleated
      cells, erythroids, megakaryocytes (Mk) and CD34+ cells. However, in contrast to
      MSCs they failed to significantly improve the expansion of hematopoietic
      progenitors. Consistent with the impact of these factors on hematopoietic cells,
      both synergized to activate ERK1/2 and AKT in primary human UCB cells. In
      conclusion, the study demonstrates for the first time that a neurotrophin factor
      can synergize with IGFBP-2 to promote hematopoietic cell expansion.

PMID- 22459635
TI  - Australian senior adventure travellers to Peru: Maximising older tourists' travel
      health experience.
AB  - Financially comfortable, with ample spare time and much better health, older
      people travel more than ever and to more adventurous destinations. Taking
      Australian senior adventure travellers to Peru as an example, travel health
      preparations need to take into account the phenomenon 'senior traveller', the
      destination with its attractions and challenges, and age-related changes and
      restrictions. The need for routine travel health advice, vaccinations and
      prophylaxis remains unchanged. However, more emphasis should be placed on
      locality-specific issues so that age-appropriate advice and preparations maximize
      the chances for a safe and memorable travel experience.

PMID- 22459636
TI  - When activation changes, what else changes? the relationship between change in
      patient activation measure (PAM) and employees' health status and health
      behaviors.
AB  - OBJECTIVE: To test whether changes in the patient activation measure (PAM) are
      related to changes in health status and healthy behaviors. METHODS: Data for this
      secondary analysis were taken from a group-randomized, controlled trial comparing
      a traditional health promotion program for employees with an activated consumer
      program and a control program. The study population included 320 employees (with
      and without chronic disease) from two U.S. companies: a large, integrated health
      care system and a national airline. Survey and biometric data were collected in
      Spring 2005 (baseline) and Spring 2007 (follow-up). RESULTS: Change in PAM was
      associated with changes in health behaviors at every level (1-4), especially at
      level 4. Changes related to overall risk score and many of its components:
      aerobic exercise, safety, cancer risk, stress and mental health. Other changes
      included frequency of eating breakfast and the likelihood of knowing about health
      plans and how they compare. CONCLUSION: Level 4 of patient activation is not an
      end-point. People are capable of continuing to make significant change within
      this level. PRACTICE IMPLICATIONS: Interventions should be designed to encourage
      movement from lower to higher levels of activation. Even people at the most
      activated level improve health behaviors.

PMID- 22459638
TI  - Correlations between ictal propagation and response to electrical cortical
      stimulation: a cortico-cortical evoked potential study.
AB  - OBJECTIVE: To better understand the process of ictal propagation in epilepsy by
      using cortico-cortical evoked potential (CCEP), which reveals the brain networks.
      METHODS: Intracranial EEG recordings of 11 seizures from 11 patients with
      pharmacoresistant focal epilepsy were studied to identify the propagation sites
      and times. Six patients had a history of secondary generalization (Gen (+) group)
      and five patients did not (Gen (-) group). Thereafter repetitive 1Hz bipolar
      electrical stimuli were applied to the ictal onset zones and CCEPs were recorded
      by averaging electrocorticograms. RESULTS: The propagation of contiguous spread
      was significantly faster than non-contiguous spread (p=0.033). In four patients,
      CCEP amplitudes were significantly larger in the ictal propagation area than out
      of the propagation area. However, the distribution of CCEP responses was not
      necessarily consistent with the ictal propagation area as a whole. Furthermore,
      the ictal propagation areas out of CCEP-positive areas were significantly broader
      in Gen (+) group than Gen (-) group (p=0.017). CONCLUSION: The present findings
      suggest that contiguous spread is faster than non-contiguous spread, which can be
      explained by the enhancement of excitability around the ictal onset area.
      Furthermore, there is a group of fibers that is "closed" during the seizures and
      secondary generalization might be more associated with the impairment of cortical
      inhibition over the broad cortical area rather than direct connection.

PMID- 22459637
TI  - Patient knowledge of blood pressure target is associated with improved blood
      pressure control in chronic kidney disease.
AB  - OBJECTIVE: To describe patient hypertension knowledge and associations with blood
      pressure measurements. METHODS: Patients with chronic kidney disease (CKD) were
      asked about the impact of high blood pressure on kidneys and their target blood
      pressure goal. Systolic blood pressure was measured using automated
      sphygmomanometers. RESULTS: In 338 adults with hypertension and pre-dialysis CKD,
      the median [IQR] age was 59 [47,68] years, 45% [n = 152] were women, and 18% [n =
      62] were non-white. Lower systolic blood pressure (SBP) was associated with
      female sex (SBP mmHg median [IQR] 132 [117,149] women vs. 137 [124,152] men; p =
      0.04), less advanced CKD (SBP 134 [122,147] stages 1-2 vs. 132 [118,148] stage 3
      vs. 140 [125,156] stages 4-5; p = 0.01), and patient ability to correctly
      identify SBP goal (SBP 134 [119,150] correct vs. 141 [125,154] incorrect; p =
      0.05). In adjusted analysis, knowledge of blood pressure goal remained
      independently associated with lower SBP (-9.96 mmHg [-19.97, -1.95] in correct
      respondents vs. incorrect; p<0.001). CONCLUSION: Patient knowledge of goal blood
      pressure is independently associated with improved blood pressure control.
      PRACTICE IMPLICATIONS: Interventions to improve patient knowledge of specific
      blood pressure targets may have an important role in optimizing blood pressure
      management.

PMID- 22459639
TI  - Surgical treatment for epilepsy in 17 children with tuberous sclerosis-related
      West syndrome.
AB  - The efficacy of surgery for the treatment of epilepsy in patients with West
      syndrome secondary to tuberous sclerosis is unclear. The charts of 17 patients
      with tuberous sclerosis and secondary West syndrome who underwent a one-stage
      surgical resection with a combined palliative operative procedure were reviewed.
      Engel classification was used to classify the patients with regard to seizure
      status following surgery. After surgery, 11 patients were in Engel class I, 4 in
      class II, and 2 in class III. The EEG after surgery was normal in 8 patients,
      significantly improved in 8, and without significant improvement in 1 patient.
      Six patients had a recurrence of seizures after surgery, which included 3
      patients with continuing spasms and 3 patients where the spasms had resolved but
      had developed either partial seizures or generalized tonic-clonic seizures. There
      were significant improvements in the Gesell Developmental Schedules for motor
      field (P=0.003), adaptive field (P=0.003), language field (P=0.033), and personal
      social field (P=0.007). Thus, a one-stage surgical approach can be used to
      produce satisfactory outcomes in young children with tuberous sclerosis who have
      secondary West syndrome and seizures that do not respond to conventional
      antiepileptic therapy, even in when there are multiple epileptogenic foci.

PMID- 22459640
TI  - Coexisting seizures in patients with infantile spasms confirmed by long-term
      video-electroencephalography monitoring.
AB  - PURPOSE: We performed this study to evaluate the frequency, types, and ictal
      electroencephalography (EEG) findings of coexisting seizures in patients with
      infantile spasms at the onset of spasms. We also evaluated the effect of
      coexisting seizures on short-term seizure control. METHODS: We retrospectively
      reviewed the long-term video-EEG and electronic medical records of 109 patients
      (58 boys and 51 girls) diagnosed with infantile spasms at the Seoul National
      University Children's Hospital. Coexisting seizure types were classified
      according to the International League Against Epilepsy seizure and epilepsy
      classification. Ictal EEG findings were also reviewed. Short-term seizure control
      rates were compared between groups with or without coexisting seizures. RESULTS:
      We identified 27 coexisting seizures in 24 of the 109 patients (22%). The most
      common type of seizure was generalized tonic seizure followed by myoclonic, focal
      tonic, tonic-clonic, hypokinetic, and versive seizures. Rates of preterm birth
      and birth asphyxia were significantly higher in patients with coexisting
      seizures. Initial anticonvulsant was vigabatrin (103 patients), valproic acid
      (five patients), and topiramate (one patient). There was no significant
      difference in short-term seizure freedom (overall seizure-free rates in patients
      without coexisting seizures vs. those with: 29.2% vs. 11.1% at 2 months, 36.1%
      vs. 22.2% at 4 months, and 41.7% vs. 27.8% at 6 months). Seizure freedom was
      significantly lower in the symptomatic groups compared with non-symptomatic
      groups. CONCLUSIONS: Long-term video-EEG monitoring is required as an initial
      evaluation in patients with infantile spasms, especially when there are reports
      of coexisting seizures, or a history of preterm birth or birth asphyxia. Presence
      of coexisting seizures was not related to poor seizure control in the short-term
      treatment period.

PMID- 22459641
TI  - [DNA methylation defects in sporadic and hereditary colorectal cancer].
AB  - DNA methylation is a fundamental epigenetic mechanism in regulating the
      expression of genes controlling crucial cell functions in cancer development.
      Methylation defects (both global hypomethylation and hypermethylation of CpG
      islands) are implicated in colorectal carcinogenesis. Some nutrients have a clear
      effect on methylation, suggesting that some dietary-associated differences in the
      incidence of colorectal cancer could be due to the effect of diet on methylation.
      The presence of methylation defects has clear diagnostic and prognostic
      implications. Thus, several tests are being used for colorectal cancer screening
      based on methylated gene analysis, whether in feces or blood. In addition, the
      reversibility of methylation processes allows the development of chemotherapies
      that regulate this process through their antineoplastic activity.

PMID- 22459642
TI  - The role of ultrasonography in early detection and monitoring of shoulder
      erosions, and disease activity in rheumatoid arthritis patients; comparison with
      MRI examination.
AB  - OBJECTIVES: To determine the accuracy of ultrasound in early detection of bone
      erosions and monitoring disease activity in rheumatoid arthritis (RA) patients
      using magnetic resonance imaging (MRI) as a gold standard technique. MATERIAL AND
      METHODS: This prospective study was carried out on 50 patients with known RA and
      15 healthy controls. Conventional radiography was standardized and performed in
      two planes. Ultrasound (US) and MRI was performed to evaluate the presence of
      synovitis, tenosynovitis, and bursitis as well as erosions on ultrasound and MRI.
      The results in the study group were compared with those obtained in a control
      group. RESULT: In the study group, the most frequent US finding of shoulder joint
      was Tenosynovitis of the long head of the biceps tendon. Tenosynovitis was
      observed in the long head of biceps tendon in 20 joints (40%). Erosions of the
      humeroscapular joint were detected by conventional radiography in 15 (30%), by US
      in 41 (82%), and by MRI in 46 (92%) of the shoulders examined, no statistically
      significant difference is noted between US and MRI in overall detection of
      erosion (P = .333). CONCLUSION: US is a helpful imaging method and in comparison
      with MRI in assessing the shoulder joint and, preferably with MRI, are
      recommended as additional techniques in the initial diagnostic evaluation when
      radiography yields negative results.

PMID- 22459643
TI  - Identifying error-making patterns in assessment of mammographic BI-RADS
      descriptors among radiology residents using statistical pattern recognition.
AB  - RATIONALE AND OBJECTIVE: The objective of this study is to test the hypothesis
      that there are patterns in erroneous assessment of BI-RADS features among
      radiology trainees when interpreting mammographic masses and that these patterns
      can be captured in individualized statistical user models. Identifying these
      patterns could be useful in personalizing and adapting educational material to
      complement the individual weaknesses of each trainee during his or her
      mammography education. MATERIALS AND METHODS: Reading data of 33 mammographic
      cases containing masses was used. The cases were individually described by 10
      radiology residents using four BI-RADS features: mass shape, mass margin, mass
      density and parenchyma density. For each resident, an individual model was
      automatically constructed that predicts likelihood (HIGH or LOW) of erroneously
      assigning each BI-RADS descriptor by the resident. Error was defined as deviation
      of the resident's assessment from the expert assessments. We evaluated the
      predictive performance of the models using leave-one-out crossvalidation.
      RESULTS: The user models were able to predict which assessments have higher
      likelihood of error. The proportion of actual errors to the number of situations
      in which these errors could potentially occur was significantly higher (P < .05)
      when user-model assigned HIGH likelihood of error than when LOW likelihood of
      error was assigned for three of the four BI-RADS features. Overall, the
      difference between the HIGH and LOW likelihood of error groups was statistically
      significant (P < .0001) combining all four features. CONCLUSION: Error making in
      BI-RADS descriptor assessment appears to follow patterns that can be captured
      with statistical pattern recognition-based user models.

PMID- 22459644
TI  - Development of a calibration phantom set for MRI temperature imaging system
      quality assurance.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) temperature imaging
      systems need to be routinely calibrated to guarantee accurate temperature results
      and qualified MRI. No independent physical temperature calibration phantom (TCP)
      set is currently available. An economical TCP set was developed to routinely
      ensure the quality of MRI temperature imaging system. MATERIALS AND METHODS: The
      novel TCP was constructed using a heating unit, temperature sensor, and MRI
      phantom liquid. A specialized heating unit was developed using carbon fibers. The
      TCP set design was an integration of the TCP, temperature measurement unit,
      display unit, and control unit. The proposed MRI calibration kit, which is a
      combination of the TCP set and standard MRI phantom, was used in the MRI
      thermometry calibration and MRI quality calibration. RESULTS: The TCP set
      provided an efficient, accurate, and homogeneous temperature map as the reference
      standard temperature for calibration. Accuracy and heating efficiency of the TCP
      set were 1 degrees C and 1 degrees C/minute, respectively. Calibration of the MRI
      thermometry and MRI quality were implemented successfully. CONCLUSION: The
      proposed TCP set is completely compatible with the MRI system and can be used to
      calibrate MRI thermometry and MRI quality to ensure the quality performance of
      the MRI temperature imaging system.

PMID- 22459645
TI  - Suspicious breast lesions detected at 3.0 T magnetic resonance imaging: clinical
      and histological outcomes.
AB  - RATIONALE AND OBJECTIVES: To evaluate the imaging features and histological and
      clinical outcomes of a series of suspicious, mammographically occult breast
      lesions detected at 3.0 T magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: Approval was obtained from the institutional review board. A Health
      Insurance Portability and Accountability Act-compliant retrospective review was
      performed of 121 suspicious, mammographically occult lesions detected on 3.0 T
      contrast-enhanced breast MRI. All 121 lesions underwent histological sampling.
      Radiology and clinic reports were reviewed for patient demographics, MRI
      indication and findings, biopsy and localization details, histological results,
      and follow-up information. Positive predictive value (PPV) of biopsy
      recommendations were calculated and compared for screening versus diagnostic
      cases. Likelihood of malignancy was also compared with lesion size. Statistical
      analyses were performed using chi-square, Fisher's exact, and two-tail z-tests.
      RESULTS: Overall 43 malignancies were diagnosed from 121 suspicious,
      mammographically occult 3.0 T MRI-detected lesions. Seventy-eight (64%) of the
      121 were benign. The overall PPV of 3.0 T MRI-detected lesions was 36% (43/121).
      The PPV for biopsy in the screening setting (22% [10/45]) was statistically
      significantly less (P = .018) compared to the PPV of a biopsy recommendation in
      the diagnostic setting (43% [33/76]). There was no correlation between lesion
      size and the likelihood of detecting malignancy. CONCLUSION: Our PPV of
      suspicious, mammographically occult, breast lesions detected at 3.0 T breast MRI
      is similar to the PPV reported previously for suspicious breast lesions detected
      at 1.5 T. This study supports the use of 3.0 T breast MRI for both screening and
      diagnostic breast imaging.

PMID- 22459646
TI  - Node/aorta and node/liver SUV ratios from (18)F-FDG PET/CT may improve the
      detection of occult mediastinal lymph node metastases in patients with non-small
      cell lung carcinoma.
AB  - RATIONALE AND OBJECTIVES: Research suggests that the semiquantitative
      determination of nodal (18)F-fluorodeoxyglucose (FDG) uptake on positron emission
      tomography (PET)/computed tomography (CT) may be useful for the assessment of
      mediastinal metastases in patients with non-small-cell lung carcinoma (NSCLC).
      The aim of this study was to evaluate the diagnostic ability of using different
      standardized uptake value (SUV) parameters in the detection of ipsilateral
      mediastinal (N2) disease. MATERIALS AND METHODS: A total of 102 patients newly
      diagnosed with non-small-cell lung carcinoma who underwent (18)F-FDG PET/CT
      before surgery and had not received prior therapy were retrospectively included.
      All patients underwent surgical resection of the primary tumor and mediastinal
      lymph node dissection. On a station-based analysis, different SUV parameters (eg,
      mediastinal lymph node SUV, node/aorta SUV ratio, and node/liver SUV ratio) were
      evaluated using the histopathologic results as the reference standard. The
      optimal cutoff value for each SUV parameter was determined with receiver
      operating characteristic curve analysis. RESULTS: The areas under the receiver
      operating characteristic curves were 0.674, 0.693, and 0.715 for node SUV,
      node/aorta SUV ratio, and node/liver SUV ratio, respectively (P < .05). With
      cutoff values of 3.15, 1.37, and 1.02 for node SUV, node/aorta SUV ratio, and
      node/liver SUV ratio, respectively, the sensitivity of (18)F-FDG PET/CT for N2
      staging was 57.1%, 85.7%, and 71.4%, and specificity was 74.2%, 50.5%, and 61.9%.
      CONCLUSIONS: Compared to node SUV alone, the use of node/aorta and node/liver SUV
      ratios resulted in improved detection of N2 metastases. The two SUV parameters
      may potentially improve the diagnostic accuracy of (18)F-FDG PET/CT for the
      diagnosis of N2 disease in patients with non-small-cell lung carcinoma.

PMID- 22459647
TI  - Electroacupuncture reduces the dose of midazolam monitored by the bispectral
      index in critically ill patients with mechanical ventilation: an exploratory
      study.
AB  - OBJECTIVE: Electroacupuncture, a modern variation on a traditional Chinese
      treatment, might be useful for sedation and analgesia. This study aims to
      investigate whether electroacupuncture can modify the dose of midazolam monitored
      by the bispectral index (BIS) in critically ill patients with mechanical
      ventilation. METHODS: Orotracheally intubated patients undergoing mechanical
      ventilation were randomly assigned into three groups (groups A, B and C). All
      patients were given an intravenous infusion of midazolam. Patients in group A
      received no additional treatment. Patients in group B were given acupuncture
      without electrical stimulation at acupuncture points GV24 and EX-HN3 (Yintang)
      for 6 h simultaneously, and patients in group C were given electroacupuncture to
      the same points as in group B. RESULTS: Maintaining the BIS between 60 and 80,
      the hourly mean one dose of midazolam within the first 6 h after sedation in
      group C was 0.05 (+/-0.02 mg/kg per hour), which was significantly lower than
      both group A (0.08 +/- 0.03 mg/kg per hour, p<0.001) and group B (0.07 +/- 0.01
      mg/kg per hour, p<0.021). The doses in groups A and B showed no significant
      difference. Between-group comparison analysis of hepatic and renal function and
      severe adverse reactions all showed no significant difference between the three
      groups. CONCLUSIONS: Electroacupuncture appears to reduce markedly the dose of
      sedative drug required in critically ill patients with mechanical ventilation
      monitored by BIS, without any obvious severe adverse action, and larger studies
      to confirm the effect are justified.

PMID- 22459648
TI  - Effects of electroacupuncture on stress-related symptoms in medical students: a
      randomised controlled pilot study.
AB  - OBJECTIVE: To assess the effects of electroacupuncture on stress-related symptoms
      sleep disorders, anxiety, depression and burnout-in medical students, and provide
      data to inform a power analysis to determinate numbers for future trials.
      METHODS: Twenty-five students were randomly assigned to an electroacupuncture
      (n=12) group or control group (n=13) that did not receive treatment.
      Electroacupuncture was applied at a continuous frequency 2 Hz for 20 min once a
      week for 8 weeks at sites on the extremities, face, ear and scalp. The outcomes
      of the students treated with electroacupuncture were compared with those of the
      control group at the endpoint, controlling the influence of baseline scores. The
      instruments used were self-administered questionnaires that comprised the
      validated Portuguese version of the mini-sleep questionnaire (MSQ), the
      Pittsburgh sleep quality index (PSQI), the Epworth sleepiness scale (ESS), the
      Beck depression inventory (BDI), the Beck anxiety inventory, the Maslach burnout
      inventory-student survey (MBI-SS), and World Health Organization quality of life
      assessment - abbreviated version (WHOQOL-bref). RESULTS: The medical students
      treated with electroacupuncture showed a significant decrease compared with the
      control group for MSQ scores (p=0.04) and PSQI (p=0.006). After treatment, 75%
      students in the electroacupuncture group presented a good sleep quality, compared
      with 23.1% of the students in the control group. No significant difference on
      daytime sleepiness was shown by the ESS. The electroacupuncture group showed
      significant improvement on depressive symptoms (BDI), the emotional exhaustion
      and cynicism dimensions of burnout (MBI-SS) and physical health (WHOQOL-bref).
      CONCLUSIONS: Electroacupuncture was associated with a significant reduction of
      stress-related symptoms, but because of the study design the authors cannot say
      what proportion of the reduction was due to needle stimulation.

PMID- 22459649
TI  - High-dose radiotherapy in inoperable nonsmall cell lung cancer: comparison of
      volumetric modulated arc therapy, dynamic IMRT and 3D conformal radiotherapy.
AB  - Conformal 3D radiotherapy (3D-CRT) combined with chemotherapy for inoperable non
      small cell lung cancer (NSCLC) to the preferable high dose is often not
      achievable because of dose-limiting organs. This reduces the probability of
      regional tumor control. Therefore, the surplus value of using intensity-modulated
      radiation therapy (IMRT) techniques, specifically volumetric modulated arc
      therapy (RapidArc [RA]) and dynamic IMRT (d-IMRT) has been investigated. RA and d
      IMRT plans were compared with 3D-CRT treatment plans for 20 patients eligible for
      concurrent high-dose chemoradiotherapy, in whom a dose of 60 Gy was not
      achievable. Comparison of dose delivery in the target volume and organs at risk
      was carried out by evaluating 3D dose distributions and dose-volume histograms.
      Quality of the dose distribution was assessed using the inhomogeneity and
      conformity index. For most patients, a higher dose to the target volume can be
      delivered using RA or d-IMRT; in 15% of the patients a dose >=60 Gy was possible.
      Both IMRT techniques result in a better conformity of the dose (p < 0.001). There
      are no significant differences in homogeneity of dose in the target volume. IMRT
      techniques for NSCLC patients allow higher dose to the target volume, thus
      improving regional tumor control.

PMID- 22459650
TI  - The use of calcium-silicate cements to reduce dentine permeability.
AB  - OBJECTIVE: To evaluate in vitro the effectiveness of different calcium-silicate
      (CS) cements specifically designed for dentine permeability reduction. DESIGN:
      Fifty dentine discs were prepared from caries free human molars extracted for
      surgical reasons. The treatment consisted in applying two different experimental
      CS cements on dentine surface. Dentine discs treated only with EDTA served as
      negative control group. Treatment with D-Sense Crystal and Clearfil S(3)-Bond
      served as positive control groups. After treatment samples were immersed in
      artificial saliva. The quantitative changes in the hydraulic conductance (i.e.
      permeability) through dentinal tubules were quantified using a hydrostatic device
      working at 6.9 kPa. Dentine permeability was measured immediately after EDTA
      treatment, 10 min and 1 week after treatment application and immersion of dentine
      samples in artificial saliva. SEM/EDX analyses were performed to obtain
      qualitative information on dentine morphology and surface deposits. RESULTS: The
      experimental CS cements reduced dentine permeability immediately after
      application and also 10 min and 1 week after the immersion of the specimens in
      artificial saliva. D-Sense Crystal and Clearfil S(3)-Bond showed higher levels of
      dentine permeability after 1 week of immersion in artificial saliva. CONCLUSIONS:
      CS cements reduced dentine permeability in vitro even after immersion in
      artificial saliva, which makes them new valuable candidates for treatment of
      dentine hypersensitivity in vivo.

PMID- 22459651
TI  - Pregnancies after transfer of vitrified blastocysts derived from vitrified
      oocytes or embryos: a small case series.

PMID- 22459652
TI  - Prediction and prevention of the macrosomic fetus.
AB  - Fetal macrosomia is associated with significant maternal and neonatal morbidity.
      In the long term, infants who are large for gestational age are more likely than
      other infants to be obese in childhood, adolescence and early adulthood, and are
      inherently at higher risk of cardiovascular and metabolic complications in
      adulthood. With over one billion adults in the world now overweight and more than
      600 million clinically obese, preventing the vicious cycle effect of fetal
      macrosomia and childhood obesity is an increasingly pertinent issue. Fetal growth
      is determined by a complex interplay of various genetic and environmental
      influences. Consequently the prediction of pregnancies at risk of pathological
      overgrowth is difficult. Many risk factors for fetal macrosomia, such as maternal
      obesity and advanced maternal age, are also conversely associated with
      intrauterine growth restriction. Sonographic detection of fetal macrosomia is
      notoriously fraught with difficulties, with dozens of formulas for estimated
      fetal weight proposed but few with sufficient sensitivity to alter clinical
      practice. This calls into question policies of elective delivery based on
      projected estimated fetal weight cut-offs alone. More recently the identification
      of markers of fetal adiposity and maternal serum biomarkers are being
      investigated to improve the antenatal detection of the large for gestational age
      fetus. Prevention of fetal macrosomia is entirely dependent upon correct
      identification of those at risk. Maternal weight, gestational weight gain and
      glycaemic control are the risk factors for fetal macrosomia that are most
      amenable to intervention, and have potential maternal health benefits beyond
      pregnancy and childbirth. The ideal method of optimising maternal weight and
      glucose homeostasis is yet to be elucidated, though a number of promising
      advances are recently being reported. In this review we outline the contemporary
      evidence for the prediction and prevention of fetal macrosomia, which is indeed a
      contemporary dilemma.

PMID- 22459653
TI  - Adnexal torsion: cystectomy and ovarian fixation are equally important in
      preventing recurrence.
AB  - OBJECTIVE: To report our clinical experience in adnexal torsion. STUDY DESIGN: A
      retrospective case review of surgically proven adnexal torsion. RESULTS: 216
      cases were identified. Mean age was 29+/-12. Twenty-two were premenarchal, 59 had
      ovarian stimulation, 48 were pregnant (with a median gestational age of 7 weeks)
      and 14 were post-menopausal. The most common risk factor was a previous history
      of adnexal torsion. The main clinical features were sudden, intermittent pain.
      Forty-five percent of Doppler examinations demonstrated normal flow: premenarchal
      and postmenopausal patients had higher rates of abnormal flow, compared to
      pregnant patients or after ovarian stimulation. Median time from admission to
      diagnosis was 6 h. Laparoscopy was conducted in 81.0% of the cases, and
      laparotomy in the rest. Twenty-three cases of recurrent torsion were documented.
      The majority of these events occurred following detorsion only. An enlarged ovary
      was found in 77 cases, dermoid cyst in 8 cases, and one case was malignant. Sixty
      eight-cases underwent detorsion, in 82 cases a combined detorsion and cystectomy
      or fenestration were performed and 43 patients underwent partial or total
      adnexectomy. Adnexal fixation was conducted in 21 cases. Cyst drainage or
      cystectomy significantly reduced the chance of retorsion by 50% and 75%,
      respectively, compared to detorsion only. CONCLUSION: Ovarian stimulation and
      early pregnancy are predisposing factors for ovarian torsion. Doppler flow
      studies may be a helpful diagnostic tool among premenarchal and post-menopausal
      women. Cystectomy should be considered in order to reduce the risk of retorsion.

PMID- 22459654
TI  - Pregnancy course and outcome in women with hereditary neuromuscular disorders:
      comparison of obstetric risks in 178 patients.
AB  - OBJECTIVE: Information about pregnancy and delivery in hereditary neuromuscular
      disorders (NMD) is limited and largely restricted to small case series and single
      case reports. Further data of obstetric histories in clinically and genetically
      defined subgroups are required. STUDY DESIGN: We reviewed the obstetric histories
      of 178 patients with myotonic dystrophy type 1 (DM1) and 2 (DM2), Charcot-Marie
      Tooth disease (CMT), spinal muscular atrophy (SMA), limb-girdle muscular
      dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), and congenital
      myopathy (CM) by means of questionnaires and medical reports. Patients were
      recruited in the period 1992-2010 after they had at least completed one
      pregnancy. A total of 380 pregnancies resulting in 315 children were documented.
      RESULTS: Compared to the normal German population, the number of miscarriages and
      hypertensive diseases in pregnancy was not increased in the cohort. Patients with
      NMD delivered more frequently by vaginal operations (8.9-18.2%) and by cesarean
      births with significantly high rates in DM1 (36.7%) and SMA (42.4%). Preterm
      deliveries were recorded in 30.7% of DM1, 12.6% of DM2, and 29.4% of SMA
      gestations. Abnormal fetal presentation occurred significantly more frequently in
      DM1 (34.6%) and LGMD (26.7%) deliveries and was a feature of chairbound patients.
      Considering a possible influence of pregnancy on the disease course, about half
      of LGMD, one-third of SMA, and one fifth of CMT patients reported a deterioration
      of symptoms in pregnancy. Neonatal outcome was favorable in all NMD but DM1,
      where infantile morbidity and mortality is often but not exclusively related to
      congenitally affected children. CONCLUSION: Our data are important for obstetric
      care and genetic counseling of women with NMD who are contemplating pregnancy.

PMID- 22459655
TI  - Anatomical variations of the proximal radius and their effects on osteosynthesis.
AB  - PURPOSE: In fractures of the radial head and neck requiring open reduction and
      internal fixation, osteosynthesis may be safely applied in a limited zone. We
      conducted a morphometric study of the proximal radius at the level of the safe
      zone to identify different morphologic types of this anatomical region. METHODS:
      We analyzed 44 dried cadaveric radii. We measured the whole length of the radius,
      the length of the neck and head, and the minimum and maximum diameter of the
      radial head. The morphologic aspect of the neck-head curvature of the safe zone
      was evaluated qualitatively and quantitatively. RESULTS: The proximal radius at
      the level of the safe zone exhibited different radii of bending. In particular,
      we identified a morphologic type A, which showed a flat profile (25% of cases),
      morphologic types B and C, which showed a low concave curvature (64%), and a
      marked concave curvature (11%), respectively, of the safe zone. CONCLUSIONS: The
      profile of the proximal radius in the safe zone shows substantial morphologic
      variations that should be taken into account when operating on fractures of the
      proximal radius, to avoid malunions, pain, and stiffness of the elbow joint. A
      preoperative radiograph of the contralateral uninjured radius may be helpful in
      selecting the most appropriate internal fixation device to reconstruct the
      proximal radius after comminuted fractures. CLINICAL RELEVANCE: Knowledge of the
      proper bending radius of the safe zone allows the surgeon to select the most
      appropriate plate, and to achieve good fracture reduction and anatomical
      restoration of the proximal radius.

PMID- 22459656
TI  - The epidemiology of reoperation after flexor tendon repair.
AB  - PURPOSE: To describe the incidence of reoperation and the demographic factors
      that may be associated with reoperation after flexor tendon repair. METHODS:
      Using a New York statewide hospital administrative database covering an 8-year
      period, we examined unique patient discharges with an index procedure of flexor
      tendon repair for reoperation (re-repair or tenolysis). We compared the age, sex,
      race, and insurance type by reoperation status using standard univariate
      statistics and multivariate regression analysis. We performed trend analysis
      using the Cochran-Armitage trend test. RESULTS: From 1998 to 2005, there were
      5,229 flexor tendon repairs with a frequency of reoperation of 6%; of these, 91%
      were in the first year after the primary procedure. Those who underwent
      reoperation were significantly older than those who did not undergo reoperation.
      Patients with workers' compensation were 63% more likely to undergo reoperation
      than those with other forms of insurance. Patients who had concomitant nerve
      repair during the index procedure were 26% less likely to undergo reoperation.
      The rate of reoperation did not change during the study period. CONCLUSIONS:
      These results may be useful in shaping research agendas to evaluate
      sociodemographic factors contributing to reoperations. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic II.

PMID- 22459657
TI  - Distal radioulnar joint stress radiography for detecting radioulnar ligament
      injury.
AB  - PURPOSE: To determine the reliability and efficacy of clenched-fist stress
      radiographs in patients with radioulnar ligament injury. METHODS: We examined 30
      patients with chronic radioulnar ligament injury. These patients underwent stress
      radiography, which included clenched-fist posteroanterior (PA) views in forearm
      pronation and computed tomography in pronation. We measured distal radioulnar
      joint (DRUJ) gap distance and ulnar variance using clenched-fist PA views. We
      measured the radioulnar ratio with pronated computed tomography to quantify
      dorsal translation of the ulnar head. We analyzed these radiographic data and
      compared them between the injured and contralateral sides. We examined test
      retest reliability and interobserver and intraobserver reliability using
      intraclass correlation coefficients as a measurement of the DRUJ gap distance in
      clenched-fist PA views. RESULTS: The DRUJ gap distance observed with clenched
      fist PA views in injured wrists was significantly greater than in the
      contralateral side. The DRUJ gap distance observed with stress radiography
      significantly correlated with the magnitude of the radioulnar ratio in forearm
      pronation. We found a significant test-retest reliability for measuring DRUJ gap
      distance using clenched-fist PA views, as well as a significant level of
      intraobserver and interobserver reliability. CONCLUSIONS: The DRUJ gap distance
      observed with clenched-fist PA radiography in forearm pronation was a reliable
      parameter and may be useful for evaluating DRUJ instability. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Diagnostic II.

PMID- 22459658
TI  - Nerve injuries resulting from arthroscopic treatment of lateral epicondylitis:
      report of 2 cases.
AB  - Arthroscopic management of lateral epicondylitis is a commonly performed
      procedure that has a good track record of efficacy and safety based on the
      current literature. Here, we report 2 cases of nerve injuries resulting from this
      operation: 1 posterior interosseous nerve transection and 1 partial median nerve
      laceration.

PMID- 22459659
TI  - A rare cause of chronic halitosis: gastric-colic fistulae.

PMID- 22459660
TI  - Lymphogranuloma venereum proctitis.

PMID- 22459661
TI  - The learning curve, accuracy, and interobserver agreement of endoscope-based
      confocal laser endomicroscopy for the differentiation of colorectal lesions.
AB  - BACKGROUND: The endoscope-based confocal laser endomicroscopy (eCLE) system
      allows in vivo imaging of colorectal epithelium. Little is known about the
      learning curve for accurate interpretation of confocal images acquired with eCLE.
      OBJECTIVE: To determine the learning curve of eCLE, its diagnostic accuracy, and
      the intra- and interobserver agreement for the differentiation of colorectal
      lesions. DESIGN: Post hoc assessment of selected eCLE images. SETTING: Academic
      centers. PATIENTS: This study involved colonoscopic images from 47 patients. MAIN
      OUTCOME MEASUREMENTS: Learning curve of eCLE, accuracy, and intraobserver and
      interobserver agreement. METHODS: Three endoscopists received a short
      introduction to eCLE before evaluating 90 images. Observers assessed all eCLE
      images by using the Mainz classification. After each set of 30 images, the
      accuracy of each observer was assessed. The same procedure was repeated 6 months
      later by using the same set of images. LIMITATIONS: Post hoc assessment. RESULTS:
      There were no significant changes between the first set of 30 images and the 2
      consecutive sets (P = .08 and P = .180, respectively). The overall accuracy was
      85.6%, 95.6%, and 92.2% for each observer. The kappa values of the intraobserver
      agreement were 0.68, 0.84, and 0.77 for each observer. The kappa value for
      interobserver agreement was 0.73 during the first and 0.72 during the second
      assessment. CONCLUSIONS: Accurate post hoc interpretation of eCLE confocal images
      can be learned quickly. High diagnostic accuracy was achieved by all 3 observers
      during the initial stage of the assessment, which remained high thereafter. Intra
      and interobserver agreement was substantial for all 3 observers. Future studies
      should focus on the real-time assessment of eCLE images.

PMID- 22459662
TI  - Endoscopic hole and clipping technique: a novel technique for closing the wide
      orifice of a postoperative fistula.
AB  - BACKGROUND: Endoscopic clipping for closing a fistula created by surgery is often
      difficult because of the combination of a wide orifice and fibrosis. Creating
      holes for prongs of a clip may constitute a new endoscopic clipping technique for
      closing the wide orifice of a fistula. OBJECTIVE: To assess the feasibility of
      performing the endoscopic hole and clipping technique (EHCT). DESIGN:
      Experimental pilot study. SETTING: Tertiary-care referral center. PATIENT: This
      study involved 1 patient who underwent EHCT. INTERVENTIONS: EHCT was performed.
      MAIN OUTCOME MEASUREMENTS: Technical success and procedural complications of
      EHCT. RESULTS: Immediately after the procedure, drainage decreased dramatically
      and finally decreased to 0 mL/d. There was no evidence of a leak on fluoroscopic
      examination, and upon 4-month follow-up, we found that no symptoms had developed
      in the patient. LIMITATIONS: Single-patient pilot study. CONCLUSIONS: EHCT is
      very simple and efficient. EHCT can be applied as a means of closing the orifice
      of a postoperative fistula that is not easily managed by simple endoscopic
      clipping.

PMID- 22459663
TI  - Submucosal tumors of the esophagogastric junction originating from the muscularis
      propria layer: a large study of endoscopic submucosal dissection (with video).
AB  - BACKGROUND: Given the high morbidity and mortality rates for surgery and the
      diminishment of quality of life caused by operative resection of the gastric
      cardia, a minor invasive treatment without loss of curability is desirable for
      submucosal tumors (SMTs) of the esophagogastric junction (EGJ). Endoscopic
      submucosal dissection (ESD) has been used successfully for the removal of
      esophageal or gastric SMTs; however, the EGJ has been regarded as a difficult
      location for ESD because of its narrow lumen and sharp angle. OBJECTIVE: To
      evaluate the clinical impact of ESD for SMTs of the EGJ arising from the
      muscularis propria layer. DESIGN: Single-center, prospective study. SETTING:
      Academic medical center. PATIENTS: 143 patients with 143 SMTs of the EGJ
      originating from the muscularis propria layer. INTERVENTIONS: ESD. MAIN OUTCOME
      MEASUREMENTS: Complications, en bloc resection rate, local recurrence, and
      distant metastases. RESULTS: The average maximum diameter of the lesions was 17.6
      mm (range 5 - 50 mm). The en bloc resection rate was 94.4% (135/143). All en bloc
      resection lesions showed both lateral and deep tumor-free margins, including 20
      GI stromal tumors. Perforations occurred in 6 patients (4.2%, 6/143), and metal
      clips were used to occlude the defect. Four pneumoperitoneum and 2 pneumothorax
      caused by perforations were resolved with nonsurgical treatment. Local recurrence
      and distant metastasis have not occurred during a 2-year follow-up. LIMITATIONS:
      Single-center, short follow-up. CONCLUSIONS: ESD appears to be a safe, feasible,
      and effective procedure for providing accurate histopathologic evaluations, as
      well as curative treatments for SMTs of the EGJ originating from the muscularis
      propria layer.

PMID- 22459664
TI  - Structural modifications of 99mTc-labelled bombesin-like peptides for optimizing
      pharmacokinetics in prostate tumor targeting.
AB  - PURPOSE: The main goal of the present study was to investigate the importance of
      the addition of a positively charged aa in the naturally occurring bombesin (BN)
      peptide for its utilization as radiodiagnostic agent, taking into consideration
      the biodistribution profile, the pharmacokinetic characteristics and the tumor
      targeting ability. METHODS: Two BN-derivatives of the general structure [M
      chelator]-(spacer)-BN(2-14)-NH(2), where M: (99m)Tc or (185/187)Re, chelator: Gly
      Gly-Cys-, spacer: -(arginine)(3)-, M-BN-A; spacer: -(ornithine)(3)-, M-BN-O; have
      been prepared and evaluated as tumor imaging agents. RESULTS: The peptides under
      study presented high radiolabelling efficiency (>98%), significant stability in
      human plasma (>60% intact radiolabelled peptide after 1h incubation) and
      comparable receptor binding affinity with the standard [(125)I-Tyr(4)]-BN. Their
      internalization rates in the prostate cancer PC-3 cells differed, although the
      amount of internalized peptide was the same. The biodistribution and the dynamic
      gamma-camera imaging studies in normal and PC-3 tumor-bearing SCID mice have
      shown significant tumor uptake, combined with fast blood clearance, through the
      urinary pathway. CONCLUSION: The addition of the charged aa spacer in the BN
      structure was advantageous for biodistribution, pharmacokinetics and tumor
      targeting ability, because it reduced the upper abdominal radioactivity levels
      and increased tumor/normal tissue contrast ratios.

PMID- 22459666
TI  - The isolated lateral malleolar fracture: where are we and how did we get here?
AB  - Despite the isolated lateral malleolar ankle fracture being one of the most
      common injuries treated by orthopaedic surgeons it remains an injury that is
      widely misunderstood. Treatment protocols are compounded by the contemporary
      literature being divided on its optimal management. This review takes the reader
      through a process of how the historical literature on this subject has been
      formed, it critiques the main responsible papers and leads one to question the
      current dogma attached to both this injury and to current research in general.

PMID- 22459665
TI  - Effects of influenza antivirals on individual and population immunity over many
      epidemic waves.
AB  - Antivirals are an important defence against novel strains of influenza. However,
      the impact of widespread drug usage on strain circulation across multiple
      epidemic waves - via their impact on host immunity - is unknown despite
      antivirals having the likelihood of extensive use during a pandemic. To explore
      how drug usage by individuals affects population strain dynamics, we embedded a
      two-strain model of within-host dynamics within an epidemic model. We found that
      when 40% of hosts took drugs early during the infectious period, transmission was
      reduced by 30% and average levels of immunity by 2.9-fold (comparable to antibody
      concentrations), relative to 14% and 1.5-fold reductions when drugs were taken
      late. The novel strain was more successful relative to the resident strain when
      drugs were not taken, and an intermediate level of drug coverage minimized
      incidence in subsequent waves. We discuss how drug regimens, coverage and R 0
      could impact pandemic preparedness.

PMID- 22459667
TI  - Review of nomenclature in colonic surgery--proposal of a standardised
      nomenclature based on mesocolic anatomy.
AB  - The standardisation of the surgical management of rectal cancer has been
      facilitated by adoption of an anatomic surgical nomenclature. Thus, "total
      mesorectal excision" substituted "anterior resection" or "proctosigmoidectomy"
      and implies resection of both rectum and mesorectum. Similar trends towards
      standardisation of colonic surgery are ongoing, yet there remains a heterogeneity
      of terminology utilised (eg, "right hemicolectomy", "ileocolic resection", and
      "total mesocolic excision"). Recent descriptions of mesocolic anatomy provide an
      opportunity to standardise colonic resection according to a more precise and
      informative anatomic nomenclature. This article aims to firstly emphasise the
      central importance of the mesocolon and from this propose a related nomenclature
      for resectional colonic surgery. Introduction of a standardised nomenclature for
      colonic resection is a necessary step towards standardisation of colonic surgery
      in general.

PMID- 22459668
TI  - Outcomes of social care for adults: developing a preference-weighted measure.
AB  - OBJECTIVE: The aim of this study was to develop a measure of social care outcome,
      an equivalent to the quality-adjusted life year (QALY) in health, which could be
      used in a range of circumstances. DESIGN: The project drew on previous and
      parallel work developing the Adult Social Care Outcome Toolkit and the national
      Adult Social Care Survey. We developed and tested an instrument designed to
      reflect service users' social care-related quality of life (SCRQoL) and tested it
      with 30 service users from a variety of user groups and 300 older home care
      service users. In parallel, we explored discrete choice experiment (DCE) and best
      worst scaling (BWS) approaches to preference elicitation with 300 members of the
      general population, and cognitively tested these with service users. We also
      cognitively tested a computer-aided time trade-off (TTO) exercise using SCRQoL
      attributes with members of the general population. In the second phase, using the
      finalised instruments, BWS interviews were conducted with 500 members of the
      general population, TTO interviews with a follow-up sample of 126 of these
      respondents, and BWS interviews with 458 people using equipment services. MAIN
      OUTCOME MEASURES: The final measure had eight domains: personal cleanliness and
      comfort, accommodation cleanliness and comfort, food and drink, safety, social
      participation and involvement, occupation, control over daily life and dignity.
      In addition to measuring current SCRQoL, the instrument includes questions used
      to establish service users' views of their 'expected' SCRQoL in the absence of
      services. The difference between a person's current and 'expected' SCRQoL
      provides an indicator of service impact. RESULTS: There was good evidence for the
      validity of the descriptive system and the validity of the current, expected and
      SCRQoL gain scales. The DCE and BWS approaches yielded similar results and, once
      introductions made clear, were understood by service users. BWS was used for the
      main stages, as it had technical and cognitive advantages. The computer-aided
      approach to TTO worked well, and respondents found questions acceptable and
      understandable. There were no substantive differences in the preferences of
      service users and the general population. The key domain was control over daily
      life, with the lowest and highest levels strongly estimated in all models. After
      allowing for observable heterogeneity, service users' preferences appeared to be
      more closely associated with their own SCRQoL than with those of the general
      population. The consistency of the results with the results of a previous study
      allowed the final model to be based on the preferences of 1000 members of the
      general population. A formula based on the relationship between TTO and BWS
      values was estimated for a social care QALY, with '0' equivalent to 'being dead'
      and '1' being the 'ideal' SCRQoL state. Members of the population experienced
      significantly higher SCRQoL than service users. CONCLUSIONS: Although further
      work is needed, particularly to develop an equivalent measure for informal carers
      and to explore the links with health QALYs, the measure has considerable
      potential. A number of methodological advances were achieved, including the first
      application of TTO in a social care context and use of BWS to establish service
      user preferences. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 22459669
TI  - Modelling soil nitrogen: the MAGIC model with nitrogen retention linked to carbon
      turnover using decomposer dynamics.
AB  - We present a new formulation of the acidification model MAGIC that uses
      decomposer dynamics to link nitrogen (N) cycling to carbon (C) turnover in soils.
      The new model is evaluated by application to 15-30 years of water chemistry data
      at three coniferous-forested sites in the Czech Republic where deposition of
      sulphur (S) and N have decreased by >80% and 40%, respectively. Sulphate
      concentrations in waters have declined commensurately with S deposition, but
      nitrate concentrations have shown much larger decreases relative to N deposition.
      This behaviour is inconsistent with most conceptual models of N saturation, and
      with earlier versions of MAGIC which assume N retention to be a first-order
      function of N deposition and/or controlled by the soil C/N ratio. In comparison
      with earlier versions, the new formulation more correctly simulates observed
      short-term changes in nitrate leaching, as well as long-term retention of N in
      soils. The model suggests that, despite recent deposition reductions and
      recovery, progressive N saturation will lead to increased future nitrate
      leaching, ecosystem eutrophication and re-acidification.

PMID- 22459670
TI  - Comparing the intended consequences of three theories of evaluation.
AB  - This paper compares selected evaluation theories (Practical Participatory
      Evaluation, Values-Engaged Evaluation, Emergent Realist Evaluation) on the basis
      of their stated consequences. The discussion follows Mark's (2008) framework for
      research on evaluation and uses Miller's (2010) criteria of discernible impact
      and reproducibility in order to delineate the theories. The research on
      evaluation outcomes shows that some of the claims made by each evaluation theory
      are supported with evidence, but many substantial claims remain untested. The
      short term and long term goals espoused by each theory show noticeable
      differences in the consequences of each evaluation approach, with different
      emphases placed on organizational capacity, use of findings, or perceptions of
      the evaluation as outcomes of the prescribed evaluation approach.

PMID- 22459671
TI  - Logic models and content analyses for the explication of evaluation theories: the
      case of emergent realist evaluation.
AB  - We comment on a set of papers in this journal issue that have examined three
      evaluation theories by constructing a logic model for each and conducting a set
      of comparative content analyses. We consider the set of papers as an instance of
      research on evaluation. For instance, we question the extent to which linear
      logic models convey the contingent decision making emphasized by some evaluation
      theories. We also offer specific comments about the papers' treatment of one
      theory, so-called emergent realist evaluation.

PMID- 22459672
TI  - Meeting report: the Schizophrenia International Research Society (SIRS) South
      America Conference (August 5-7, 2011).
AB  - On August 5-7, 2011, Sao Paulo was home to the first regional meeting of the
      Schizophrenia International Research Society (SIRS). Over 400 people from many
      countries attended the activities and contributed with around 200 submissions for
      oral and poster presentations. This article summarizes the data presented during
      the meeting, with an emphasis on the plenary talks and sessions for short oral
      presentations. For information on the poster presentations, readers are referred
      to the special issue of Revista de Psiquiatria Clinica (Brazil) dedicated to the
      conference (available at: http://www.hcnet.usp.br/ipq/revista/vol38/s1/).

PMID- 22459673
TI  - Adult manifestation of L-2-hydroxyglutarate dehydrogenase deficiency by a novel
      mutation.

PMID- 22459674
TI  - Poststroke depression and emotional incontinence: factors related to acute and
      subacute stages.
AB  - OBJECTIVES: To investigate the characteristics and prevalence of poststroke
      depression (PSD) and poststroke emotional incontinence (PSEI) and the factors
      related to these conditions at admission and 3 months after stroke. METHODS: We
      evaluated 508 consecutive patients with acute ischemic stroke for PSD and PSEI at
      admission and 3 months later. PSD was evaluated using the Beck Depression
      Inventory, and PSEI was evaluated using Kim's criteria. Blood samples were
      collected and genotyped for the promoter region of the serotonin transporter
      protein (5-HTTLPR) and the number of tandem repeats within intron 2 (STin2 VNTR).
      Perceived social support (the ENRICHD Social Support Inventory) was also
      measured. RESULTS: PSD and PSEI were present in 13.7% and 9.4% of patients,
      respectively, at admission and in 17.7% and 11.7%, respectively, at 3 months
      after stroke. Multivariate analyses showed that PSD at admission was associated
      with the NIH Stroke Scale score at admission (p < 0.001), whereas PSD at 3 months
      was associated with the presence of microbleeds (p < 0.01) and perceived low
      social support (p < 0.001). In contrast, only lesion location (p = 0.022) was
      associated with PSEI at admission, whereas modified Rankin Scale score (p =
      0.019), STin2 VNTR (p = 0.040), and low social support (p = 0.042) were related
      to PSEI 3 months after stroke. CONCLUSIONS: Diverse factors such as neurologic
      dysfunction, lesion location, microbleeds, genetic traits, and social support are
      differently related to acute and subacute emotional disturbances. Strategies to
      prevent or manage these problems should consider these differences.

PMID- 22459675
TI  - Activity enhances dopaminergic long-duration response in Parkinson disease.
AB  - OBJECTIVE: We tested the hypothesis that dopamine-dependent motor learning
      mechanism underlies the long-duration response to levodopa in Parkinson disease
      (PD) based on our studies in a mouse model. By data-mining the motor task
      performance in dominant and nondominant hands of the subjects in a double-blind
      randomized trial of levodopa therapy, the effects of activity and dopamine
      therapy were examined. METHODS: We data-mined the Earlier versus Later Levodopa
      Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed
      statistical analysis comparing the effects of levodopa and dominance of
      handedness over 42 weeks. RESULTS: The mean change in finger-tapping counts from
      baseline before the initiation of therapy to predose at 9 weeks and 40 weeks
      increased more in the dominant compared to nondominant hand in levodopa-treated
      subjects in a dose-dependent fashion. There was no significant difference in
      dominant vs nondominant hands in the placebo group. The short-duration response
      assessed by the difference of postdose performance compared to predose
      performance at the same visit did not show any significant difference between
      dominant vs nondominant hands. CONCLUSIONS: Active use of the dominant hand and
      dopamine replacement therapy produces synergistic effect on long-lasting motor
      task performance during "off" medication state. Such effect was confined to
      dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as
      gait and balance. We propose that long-lasting motor learning facilitated by
      activity and dopamine is a form of disease modification that is often seen in
      trials of medications that have symptomatic effects.

PMID- 22459676
TI  - Clinical spectrum of CNS aquaporin-4 autoimmunity.
AB  - OBJECTIVES: Traditionally, neuromyelitis optica (NMO) was known to involve only
      the optic nerves and spinal cord. However, the discovery of highly specific anti
      aquaporin-4 (AQP4) antibody for NMO enabled us to identify more diverse clinical
      manifestations. Here, we describe the demographic and clinical characteristics of
      patients who were anti-AQP4-antibody positive, represented by CNS AQP4
      autoimmunity. METHODS: In total, 388 consecutive patients with inflammatory
      demyelinating CNS diseases were tested for the anti-AQP4 antibody and 106
      seropositive patients who were positive by ELISA or cell-based assay were
      included. RESULTS: Ninety-seven patients were women, and 9 men. The median age at
      onset was 32 years. The median annualized relapse rate was 1.14 during the median
      follow-up of 7.0 years. When the 2006 revised diagnostic criteria for NMO were
      applied, 72% of patients met the criteria, and 28% had a limited form of NMO.
      Brain symptoms were observed in 51% of patients, and 24% of patients presented
      with brain symptoms as their first manifestation. Severe residual visual
      impairment or ambulatory disability was observed in 42% of patients. The median
      intervals to Expanded Disability Status Scale (EDSS) 6 and severe visual
      impairment in at least one eye were 12 and 11 years, respectively. A multivariate
      analysis revealed a delay of more than 4 years before appropriate immunotherapy
      was independently associated with reaching severe disability of more than EDSS 6.
      CONCLUSION: The spectrum of neurologic manifestations and the disease course
      associated with CNS AQP4 autoimmunity is broader than previously recognized.

PMID- 22459678
TI  - Radiotherapy for AVM-related epilepsy: beaming the seizure away?

PMID- 22459677
TI  - Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.
AB  - OBJECTIVE: To identify the gene responsible for 14q32-linked dominant spinal
      muscular atrophy with lower extremity predominance (SMA-LED, OMIM 158600).
      METHODS: Target exon capture and next generation sequencing was used to analyze
      the 73 genes in the 14q32 linkage interval in 3 SMA-LED family members. Candidate
      gene sequencing in additional dominant SMA families used PCR and pooled target
      capture methods. Patient fibroblasts were biochemically analyzed. RESULTS:
      Regional exome sequencing of all candidate genes in the 14q32 interval in the
      original SMA-LED family identified only one missense mutation that segregated
      with disease state-a mutation in the tail domain of DYNC1H1 (I584L). Sequencing
      of DYNC1H1 in 32 additional probands with lower extremity predominant SMA found 2
      additional heterozygous tail domain mutations (K671E and Y970C), confirming that
      multiple different mutations in the same domain can cause a similar phenotype.
      Biochemical analysis of dynein purified from patient-derived fibroblasts
      demonstrated that the I584L mutation dominantly disrupted dynein complex
      stability and function. CONCLUSIONS: We demonstrate that mutations in the tail
      domain of the heavy chain of cytoplasmic dynein (DYNC1H1) cause spinal muscular
      atrophy and provide experimental evidence that a human DYNC1H1 mutation disrupts
      dynein complex assembly and function. DYNC1H1 mutations were recently found in a
      family with Charcot-Marie-Tooth disease (type 2O) and in a child with mental
      retardation. Both of these phenotypes show partial overlap with the spinal
      muscular atrophy patients described here, indicating that dynein dysfunction is
      associated with a range of phenotypes in humans involving neuronal development
      and maintenance.

PMID- 22459679
TI  - If at first you don't succeed, test again (for peroxisomal biogenesis disorders).

PMID- 22459681
TI  - MRI as diagnostic tool in early-onset peroxisomal disorders.
AB  - OBJECTIVE: Peroxisomal blood tests are generally considered to be conclusive. We
      observed several patients with a clinical and MRI phenotype suggestive of an
      infantile onset peroxisomal defect, but no convincing abnormalities in initial
      peroxisomal blood tests. Brain MRI showed typical abnormalities as observed in
      the neonatal adrenoleukodystrophy variant of infantile peroxisomal disorders. Our
      aim was to evaluate the accuracy of this MRI diagnosis with further peroxisomal
      testing. METHODS: We searched our database of unclassified leukoencephalopathies
      and found 6 such patients. We collected clinical data and scored available MRIs
      of these patients. We performed further peroxisomal studies in fibroblasts,
      including immunofluorescence microscopy analysis with antibodies against
      catalase, a peroxisomal matrix enzyme. We performed complementation analysis and
      analyzed the suspected genes. RESULTS: We confirmed the diagnosis of Zellweger
      spectrum disorder in 3 patients and D-bifunctional protein deficiency in the
      others. The clinical findings were within the spectrum known for these diagnoses.
      Sequential MRIs showed that the abnormalities started in the hilus of the dentate
      nucleus and superior cerebellar peduncles. Subsequently, the cerebellar white
      matter and brainstem tracts were affected, followed by the parieto-occipital
      white matter, splenium of the corpus callosum, and posterior limb of the internal
      capsule. Eventually, all cerebral white matter became abnormal. The thalamus was
      typically affected as well. CONCLUSIONS: If MRI reveals abnormalities suggestive
      of infantile onset peroxisomal defects, negative peroxisomal blood tests do not
      exclude the diagnosis. Further tests in fibroblasts should be performed, most
      importantly immunofluorescence microscopy analysis with antibodies against
      catalase to stain peroxisomes.

PMID- 22459682
TI  - The frontal lobe in absence epilepsy: EEG-fMRI findings.
AB  - OBJECTIVE: Studies of absence seizures (AS) using EEG with fMRI (EEG-fMRI) show a
      consistent network with prominent thalamic activation and a variety of cortical
      changes. Despite evidence suggesting a role of frontal cortex in seizure
      generation, group studies have not detected consistent AS-related changes in this
      region. We hypothesized that only a subgroup may show frontal cortical
      activation. METHOD: We studied 13 subjects with AS during EEG-fMRI to classify
      the different individual patterns of frontal cortical activation associated with
      AS. RESULTS: Based upon visual inspection of surface-rendered activation maps we
      identified 2 subgroups that could be distinguished by the activation in the
      dorsolateral prefrontal cortex (DLPFC). One group of patients (n = 7) showed a
      primarily positive signal change (DLPFC-POS), whereas the other group (n = 6)
      showed a primarily negative signal change (DLFPC-NEG). When the DLPFC-POS group
      was compared to the DLPFC-NEG group, time-course analysis revealed a larger
      positive blood oxygenation level-dependent deflection following onset of the AS
      in cortical and subcortical areas beyond the DLPFC. This suggests a basic
      biological difference between these groups. CONCLUSION: These observations
      suggest that there may be at least 2 mechanisms underpinning AS in individuals
      with absence epilepsy. This may have phenotypic and genetic implications for
      understanding epilepsy syndromes.

PMID- 22459680
TI  - Randomized controlled trial of atorvastatin in clinically isolated syndrome: the
      STAyCIS study.
AB  - OBJECTIVE: To test efficacy and safety of atorvastatin in subjects with
      clinically isolated syndrome (CIS). METHODS: Subjects with CIS were enrolled in a
      phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80
      mg atorvastatin on clinical and brain MRI activity. Brain MRIs were performed
      quarterly. The primary endpoint (PEP) was development of >= 3 new T2 lesions, or
      one clinical relapse within 12 months. Subjects meeting the PEP were offered
      additional weekly interferon beta-1a (IFNbeta-1a). RESULTS: Due to slow
      recruitment, enrollment was discontinued after 81 of 152 planned subjects with
      CIS were randomized and initiated study drug. Median (interquartile range)
      numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0
      (0.0) at baseline. A total of 53.1% of atorvastatin recipients (n = 26/49) met
      PEP compared to 56.3% of placebo recipients (n = 18/32) (p = 0.82). Eleven
      atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by
      clinical criteria. Proportion of subjects who did not develop new T2 lesions up
      to month 12 or to starting IFNbeta-1a was 55.3% in the atorvastatin and 27.6% in
      the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was
      significantly greater in the atorvastatin group compared with placebo (odds ratio
      [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be
      higher in the atorvastatin group (OR = 2.72, p = 0.11). Overall, atorvastatin was
      well tolerated. No clear antagonistic effect of atorvastatin plus IFNbeta-1a was
      observed on MRI measures. CONCLUSION: Atorvastatin treatment significantly
      decreased development of new brain MRI T2 lesion activity, although it did not
      achieve the composite clinical and imaging PEP. CLASSIFICATION OF EVIDENCE: This
      study provided Class II evidence that atorvastatin did not reduce the proportion
      of patients with CIS meeting imaging and clinical criteria for starting
      immunomodulating therapy after 12 months, compared to placebo. In an analysis of
      a secondary endpoint (Class III), atorvastatin was associated with a reduced risk
      for developing new T2 lesions.

PMID- 22459683
TI  - Long-term risk of developing epilepsy after febrile seizures: a prospective
      cohort study.
AB  - OBJECTIVE: We report the prospective follow-up of a cohort of people from the
      onset of febrile seizures for a median of 24 years to estimate the long-term risk
      of developing epilepsy. METHODS: The National General Practice Study of Epilepsy
      is a large prospective community study of 1,195 people with a first suspected
      seizure followed from the 1980s, of whom 220 (18%) had febrile seizures.
      Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for
      subsequent epilepsy were calculated in 5-year age bands. RESULTS: Follow-up
      information was obtained for 181 (83%) people with a mean follow-up for the whole
      cohort of 21.6 (SD 6.0) years. Of these, 175 (97%) were seizure-free in the
      preceding 5 years, whereas 171 (94%) were seizure-free and off antiepileptic
      drugs. Six percent developed epilepsy, but the risk of developing epilepsy in the
      cohort over the whole follow-up period was almost 10 times that of the general
      population (SIR 9.7, 95% CI 5.7-16.4). The SIR was significantly elevated in the
      0- to 14-year age groups but not in the 15- to 19-year age group (SIR 4.5, 95% CI
      0.6-32.1). CONCLUSION: The risk of developing epilepsy in people who had febrile
      seizures seems to decrease with time. Further long-term studies are needed to
      confirm this.

PMID- 22459684
TI  - A calm before the exome storm: coming together of dSMA and CMT2.

PMID- 22459685
TI  - Radiosurgery for unruptured cerebral arteriovenous malformations: long-term
      seizure outcome.
AB  - OBJECTIVE: To date, seizures in relation to arteriovenous malformations (AVM)
      have been a secondary target of most studies. The insufficient evaluation, in
      conjunction with the lack of consistent seizure outcome assessment, has made it
      been difficult to draw conclusions about seizure outcome after radiosurgery for
      AVM. This study aimed to determine the effect of radiosurgery on seizure outcome
      depending on AVM obliteration and on the development of new seizure in patients
      with AVM. METHODS: Between 1997 and 2006, 161 consecutive patients underwent
      radiosurgery for unruptured AVM and were retrospectively assessed with a mean
      follow-up of 89.8 months by their medical records, updated clinical information,
      and, when necessary, direct patient contact. Seizure outcome was assessed using
      the Engel seizure frequency scoring system. RESULTS: Of the 86 patients with a
      history of seizure before radiosurgery, 76.7% (66/86) were seizure-free and 58.1%
      (50/86) were medication-free at the last follow-up visit. Of the patients who
      achieved AVM obliteration, 96.7% (58/60) were seizure-free while 30.8% (8/26) of
      those patients who did not achieve AVM obliteration were seizure-free (p =
      0.001). The proportion of patients who were medication-free was 81.7% (49/60) of
      the patients with obliteration and 3.8% (1/26) of patients without obliteration
      (p < 0.001). Of the 75 patients with no history of seizure before radiosurgery,
      10 had provoked seizures due to the direct and indirect radiosurgical influences
      after radiosurgery. CONCLUSIONS: Although radiosurgery tends to cause seizures
      temporarily, the radiosurgery may improve seizure outcomes in patients with AVM
      related seizures, especially in patients with AVM obliteration.

PMID- 22459687
TI  - [Clinical forms and treatment of infections caused by other filamentous fungi].
AB  - An increase in infections by filamentous fungi other than Aspergillus has been
      observed in the last few years. Clear fungi or hyalohyphomycetes, dematiaceous or
      dark fungi, agents of mucormycosis, and Pneumocystis jirovecii are generally
      emerging opportunistic fungi that produce disseminated infection in patients with
      severe immunosuppression. The clinical manifestations in this group of patients
      are often non-specific as their expression is modified by the disease itself or
      by the concomitant treatments, which difficult early diagnosis. This, together
      with the relatively limited therapeutic resources available, has led to invasive
      fungal infections by these filamentous fungi being associated with significant
      mortality (30-100%). Nowadays with the emergence of the new triazole drugs or
      lipid formulations of amphotericin B, often combined with other antifungal drugs,
      attempts are being made to change the dire prognosis of patients with these
      infections.

PMID- 22459686
TI  - Outcomes in HIV-infected patients admitted due to pandemic influenza.
AB  - PURPOSE: To determine the clinical, epidemiological and prognostic factors of HIV
      infected patients with influenza A H1N1 admitted to hospital. METHODS: The study
      population was HIV infected patients with confirmed influenza infection admitted
      to hospital in a multicenter cohort. We analyzed demographic data, comorbid
      conditions, severe events (bronchopneumonia, respiratory insufficiency,
      respiratory distress, sepsis, admission to intensive care unit, death) and
      outcome. Data were analyzed using descriptive statistics. Proportions were
      compared using the chi(2) test or Fisher exact test, when applicable.
      Quantitative variables were compared using the Student t test or Mann-Whitney
      test. Prognostic impact was analyzed using logistic regression. RESULTS: A total
      of 43 patients, of whom 62.8% were male, were included from 22 hospitals. The
      mean age was 43.3 years (interquartile range [IQR], 38.4-48.4). HIV was diagnosed
      for a mean of 14.5 years (IQR, 8.4-20.3). CD4 lymphocyte was <200 cells/MUL in
      38%; 85.7% were on antiretroviral therapy, and 66.7% virologically suppressed.
      Comorbid conditions were hepatitis B or C (74.4%), smoking (67.4%), chronic
      obstructive pulmonary disease (30.2%), asthma (14%), and obesity (8.6%). Seven
      patients had received seasonal influenza vaccination, and 2 the H1N1 vaccine.
      Cough (100%), fever (93%), gastrointestinal disorders (27.9%) or general-
      myalgia, general malaise--(67.4%) were the presenting symptoms. These were severe
      in 24 (55.8%) with 7 (16.3%) requiring intensive care. Two patients died. A lower
      CD4 lymphocyte count was associated with bacterial infection (P=.063) and longer
      hospital stay (P=.007). Early oseltamivir reduced severe cases (OR, 4.5; 1.1
      18.3; P=.035). CONCLUSIONS: HIV-infected patients admitted to hospital due to
      influenza A H1N1 had severe morbidity. Low CD4 lymphocytes correlated with longer
      hospitalization and bacterial infections. Early oseltamivir treatment reduced
      severe symptoms.

PMID- 22459688
TI  - [Candidemia and invasive candidiasis in the adult: clinical forms and treatment].
AB  - Invasive candidiasis is progressively increasing in frequency as a complication
      of the hospitalised adult patient. The availability of new antifungal drugs with
      lower toxicity and high efficacy has increased the complexity of managing of
      these infections. In parallel, the costs of the treatment of invasive fungal
      infections have considerably increased. Finding of a balance between the best
      benefit for the patient with the less costs is, nowadays, one of the main
      objectives of the current recommendations for the management of invasive
      candidiasis. In this review, the recommendations for the management of candidemia
      and other forms of invasive candidiasis (esophagitis, peritonitis, ocular,
      cardiovascular and osteoarticular candidiasis, central nervous system and urinary
      tract candidiasis, and chronic disseminated candidiasis) are analysed.

PMID- 22459690
TI  - Neuroethology.

PMID- 22459691
TI  - Thirty years of research on infection and prostate cancer: no conclusive evidence
      for a link. A systematic review.
AB  - BACKGROUND: The potential role of genitourinary infection in the etiology of
      prostate cancer (CaP) has been extensively investigated for 30 years. Two basic
      approaches have been used: tissue-based methods (polymerase chain reaction,
      immunohistochemistry, and in situ hybridization) and serologic assays (enzyme
      linked immunosorbent assay, immunofluorescence, etc.). The objective of this
      review was to answer the question of whether infection of the male genitourinary
      tract may have a role in the etiology of CaP. MATERIALS AND METHODS: We have
      carried out a systematic review of the evidence that was published in the
      MEDLINE/PubMed database until December 2011. The search terms included "prostate
      cancer," "infection," and the explicit names of the various infectious agents.
      Additional studies were identified using a reference search. A total of 74 papers
      were included in the review, which cover the following infectious agents: human
      papillomavirus, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, human
      herpesvirus, BK virus, JC virus, chlamydia, mycoplasma, ureaplasma, trichomonas,
      neisseria, treponema, Propionibacterium acnes, xenotropic murine leukemia virus
      related virus and Candida albicans. RESULTS: Despite the variable study designs
      and methodological approaches that were used, most of the pathogens that were
      studied were unlikely to be directly involved in prostate carcinogenesis.
      CONCLUSIONS: The role of infection in the etiology of CaP has yet to be
      determined despite 30 years of research efforts. A discovery of an infectious
      agent that is associated with CaP would be of great medical importance; however,
      such a link would have to be firmly established before impacting on patient care.

PMID- 22459689
TI  - Signaling in dendritic spines and spine microdomains.
AB  - The specialized morphology of dendritic spines creates an isolated compartment
      that allows for localized biochemical signaling. Recent studies have revealed
      complexity in the function of the spine head as a signaling domain and indicate
      that (1) the spine is functionally subdivided into multiple independent
      microdomains and (2) not all biochemical signals are equally compartmentalized
      within the spine. Here we review these findings as well as the developments in
      fluorescence microscopy that are making possible direct monitoring of signaling
      within spines and, in the future, within sub-spine microdomains.

PMID- 22459692
TI  - Molecular dynamics simulations of the coenzyme induced conformational changes of
      Mycobacterium tuberculosis L-alanine dehydrogenase.
AB  - Mycobacterium tuberculosis L-alanine dehydrogenase (L-MtAlaDH) catalyzes the NADH
      dependent reversible oxidative deamination of L-alanine to pyruvate and ammonia.
      L-MtAlaDH has been proposed to be a potential target in the treatment of
      tuberculosis. Based on the crystal structures of this enzyme, molecular dynamics
      simulations were performed to investigate the conformational changes of L-MtAlaDH
      induced by coenzyme NADH. The results show that the presence of NADH in the
      binding domain restricts the motions and conformational distributions of L
      MtAlaDH. There are two loops (residues 94-99 and 238-251) playing important roles
      for the binding of NADH, while another loop (residues 267-293) is responsible for
      the binding of substrate. The opening/closing and twisting motions of two domains
      are closely related to the conformational changes of L-MtAlaDH induced by NADH.

PMID- 22459693
TI  - Do personality traits moderate the impact of care receipt on end-of-life care
      planning?
AB  - PURPOSE OF THE STUDY: This study examines (a) the association between being a
      care recipient and end-of-life care planning (EOLCP) and (b) the extent to which
      personality traits moderate the relationship between care receipt and EOLCP.
      DESIGN AND METHODS: Data are drawn from the Wisconsin Longitudinal Study, a
      survey of Wisconsin high school graduates from 1957 to 2004. We used data on
      EOLCP among older adults in the most recent (2003-2004) wave of this survey.
      Hierarchical logistic regression models are used to estimate the effects of care
      receipt and the moderating effects of personality. RESULTS: Compared with their
      peers who are not receiving care, care recipients are more likely to engage in
      informal discussion on EOLCP. This association between care receipt and informal
      EOLCP is strengthened when the individual scores high on openness. IMPLICATIONS:
      Health practitioners should take into account older adults' care needs and
      differing personality traits while helping older adults make successful EOLCP.

PMID- 22459695
TI  - Clustering very low-income, insured women's mammography screening barriers into
      potentially functional subgroups.
AB  - BACKGROUND: Mammography screening is essential for early detection of breast
      cancer and increased survival rates. Women, particularly those of low
      socioeconomic status, face barriers that impede their screening adherence.
      Although many studies have sought to identify these barriers, more research is
      needed on to address these obstacles in practice. The objective of this study is
      to divide mammography screening barriers into functional clusters using empirical
      evidence, which may guide the development of effective mammography screening
      promotion messages. METHODS: A sample of 173 low-income White and Black women
      randomly selected from a managed care organization rated each of 21 potential
      mammography barriers on a scale ranging from "strongly agree" to "strongly
      disagree." A maximum clustering similarity method was used to identify relevant
      clusters of screening barriers. RESULTS: Five clusters were derived, with a high
      similarity index (0.881). Each cluster was named to reflect the shared theme of
      the barriers within it: Perceived Lack of Value in Health Care, Lack of
      Information, Mistrust/Skepticism, Medical Delay Behavior, and Anxiety/No Control.
      A dominant barrier within each cluster was identified, and bivariate correlation
      coefficients were reported. CONCLUSION: Cluster analysis yielded five distinct
      subgroups of mammography screening barriers.

PMID- 22459694
TI  - Do nurse-led skill training interventions affect informal caregivers' out-of
      pocket expenditures?
AB  - PURPOSE OF THE STUDY: This paper is a report of a study of the Assistance,
      Support, and Self-health Initiated through Skill Training (ASSIST) randomized
      control trial. The aim of this paper is to understand whether participating in
      ASSIST significantly changed the out-of-pocket (OOP) costs for family caregivers
      of Alzheimer's disease (AD) or Parkinson's disease (PD) patients. DESIGN AND
      METHODS: Secondary analysis of randomized control trial data, calculating average
      treatment effects of the intervention on OOP costs. Enrollment in the ASSIST
      trial occurred between 2002 and 2007 at 2 sites: Durham, North Carolina, and
      Birmingham, Alabama. We profile OOP costs for caregivers who participated in the
      ASSIST study and use 2-part expenditure models to examine the average treatment
      effect of the intervention on caregiver OOP expenditures. RESULTS: ASSIST-trained
      AD and PD caregivers reported monthly OOP expenditures that averaged $500-$600.
      The intervention increased the likelihood of caregivers spending any money OOP by
      26 percentage points over usual care, but the intervention did not significantly
      increase overall OOP costs. IMPLICATIONS: The ASSIST intervention was effective
      and inexpensive to the caregiver in direct monetary outlays; thus, there are
      minimal unintended consequences of the trial on caregiver financial well-being.

PMID- 22459696
TI  - Analysis of early biochemical markers and regulation by tin protoporphyrin IX in
      a model of spontaneous osteoarthritis.
AB  - Age-related changes in joint tissues lead to osteoarthritis (OA). Detection of
      early changes in OA patients may help to initiate treatments before the
      establishment of irreversible joint destruction. STR/ort mice develop with age a
      severe degenerative joint disease that resembles human OA thus allowing the
      investigation of biochemical markers as well as new treatments in an accelerated
      time frame. We have analyzed the changes in serum levels of different mediators
      during the early phases of idiopathic OA in STR/ort mice. Serum levels of matrix
      metalloproteinase-3 (MMP-3) but not those of tumor necrosis factor-alpha,
      interleukin(IL)-1beta, IL-17 or prostaglandin E(2) correlated with
      histopathological changes in knees of STR/ort mice at 9 weeks. Treatment of
      animals with tin protoporphyrin IX (SnPP, 12 mg/kg/dayi.p.) for 4 weeks
      significantly reduced the progression of OA. Our data suggest that MMP-3 is a
      sensitive biomarker to detect early OA alterations and that SnPP could be a
      protective agent in OA.

PMID- 22459697
TI  - Robotic resistance treadmill training improves locomotor function in human spinal
      cord injury: a pilot study.
AB  - OBJECTIVE: To determine whether cable-driven robotic resistance treadmill
      training can improve locomotor function in humans with incomplete spinal cord
      injury (SCI). DESIGN: Repeated assessment of the same patients with crossover
      design. SETTING: Research units of rehabilitation hospitals in Chicago.
      PARTICIPANTS: Patients with chronic incomplete SCI (N=10) were recruited to
      participate in this study. INTERVENTIONS: Subjects were randomly assigned to 1 of
      2 groups. One group received 4 weeks of assistance training followed by 4 weeks
      of resistance training, while the other group received 4 weeks of resistance
      training followed by 4 weeks of assistance training. Locomotor training was
      provided by using a cable-driven robotic locomotor training system, which is
      highly backdrivable and compliant, allowing patients the freedom to voluntarily
      move their legs in a natural gait pattern during body weight supported treadmill
      training (BWSTT), while providing controlled assistance/resistance forces to the
      leg during the swing phase of gait. MAIN OUTCOME MEASURES: Primary outcome
      measures were evaluated for each participant before training and after 4 and 8
      weeks of training. Primary measures were self-selected and fast overground
      walking velocity and 6-minute walking distance. Secondary measures included
      clinical assessments of balance, muscle tone, and strength. RESULTS: A
      significant improvement in walking speed and balance in humans with SCI was
      observed after robotic treadmill training using the cable-driven robotic
      locomotor trainer. There was no significant difference in walking functional
      gains after resistance versus assistance training, although resistance training
      was more effective for higher functioning patients. CONCLUSIONS: Cable-driven
      robotic resistance training may be used as an adjunct to BWSTT for improving
      overground walking function in humans with incomplete SCI, particularly for those
      patients with relatively high function.

PMID- 22459699
TI  - Comparison of the efficacy of transcutaneous electrical nerve stimulation,
      interferential currents, and shortwave diathermy in knee osteoarthritis: a double
      blind, randomized, controlled, multicenter study.
AB  - OBJECTIVE: To compare the effectiveness of transcutaneous electrical nerve
      stimulation (TENS), interferential currents (IFCs), and shortwave diathermy (SWD)
      against each other and sham intervention with exercise training and education as
      a multimodal package. DESIGN: A double-blind, randomized, controlled, multicenter
      trial. SETTING: Departments of physical medicine and rehabilitation in 4 centers.
      PARTICIPANTS: Patients (N=203) with knee osteoarthritis (OA). INTERVENTIONS: The
      patients were randomized by the principal center into the following 6 treatment
      groups: TENS sham, TENS, IFCs sham, IFCs, SWD sham, and SWD. All interventions
      were applied 5 times a week for 3 weeks. In addition, exercises and an education
      program were given. The exercises were carried out as part of a home-based
      training program after 3 weeks' supervised group exercise. MAIN OUTCOME MEASURES:
      Primary outcome was a visual analog scale (0-100mm) to assess knee pain. Other
      outcome measures were time to walk a distance of 15m, range of motion, Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Nottingham Health
      Profile, and paracetamol intake (in grams). RESULTS: We found a significant
      decrease in all assessment parameters (P<.05), without a significant difference
      among the groups except WOMAC stiffness score and range of motion. However, the
      intake of paracetamol was significantly lower in each treatment group when
      compared with the sham groups at 3 months (P<.05). Also, the patients in the IFCs
      group used a lower amount of paracetamol at 6 months (P<.05) in comparison with
      the IFCs sham group. CONCLUSIONS: Although all groups showed significant
      improvements, we can suggest that the use of physical therapy agents in knee OA
      provided additional benefits in improving pain because paracetamol intake was
      significantly higher in the patients who were treated with 3 sham interventions
      in addition to exercise and education.

PMID- 22459698
TI  - The trajectory of physical and mental health from injury to 5 years after
      multiple trauma: a prospective, longitudinal cohort study.
AB  - OBJECTIVES: To describe the trajectory of physical and mental health from injury
      to 5 years postinjury for patients with multiple trauma, and to examine
      predictors of recovery of physical and mental health. DESIGN: A prospective,
      longitudinal cohort study with data from injury (baseline), the return home (t1),
      and 1 (t2), 2 (t3), and 5 (t4) years. SETTING: Hospital and community setting.
      PARTICIPANTS: Patients (N=105; mean age +/- SD, 35.3+/-14.0y; age range, 18-67y;
      83% men) with multiple trauma and a New Injury Severity Score (NISS) >=16 treated
      at a regional trauma referral center. Mean NISS +/- SD was 34.6+/-12.6, and mean
      Glasgow Coma Scale (GCS) score +/- SD was 12.2+/-3.9. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Medical Outcomes Study 36-Item Short-Form
      Health Survey physical component summary (PCS) and mental component summary
      (MCS), injury severity parameters, and World Health Organization Disability
      Assessment Schedule II (WHODAS II) for activities and participation. RESULTS: The
      proportion with poor physical health (<40 points on the PCS) stabilized at 56% at
      t4 from 81% at t1. The proportion with poor mental health (<40 points on the MCS)
      stabilized at 31% at t4 from 43% at t1. Generalized estimating equations showed
      that predictors of PCS were time points of measurement (Wald, 85.50; P<.001), GCS
      (B=-.48, P=.004), time in hospital/rehabilitation (B=-.22, P=.001), and the rank
      transformed WHODAS II subscales Getting around (B=.16, P<.001) and Participation
      in society (B=.06, P=.015). Predictors of MCS were time points of measurement
      (Wald 13.46, P=.004), sex (men/women) (B=-4.24, P=.003), education (low/high)
      (B=3.43, P=.019), and WHODAS II cognitive function (B=.18, P<.001) and
      Participation in society (B=.18, P<=.001). CONCLUSIONS: Physical and mental
      health over the 5 years improved with time, but was still significantly below
      population means. The physical and mental health status stabilized, but the
      recovery trajectories differed for physical and mental health. Predictors of
      health were personal and injury-related factors and function in a biopsychosocial
      perspective.

PMID- 22459700
TI  - Short-term effects of 890-nanometer radiation on pain, physical activity, and
      postural stability in patients with knee osteoarthritis: a double-blind,
      randomized, placebo-controlled study.
AB  - OBJECTIVE: To investigate the effects of short-term light therapy with 890-nm
      radiation on pain, physical activity, and postural stability in patients with
      knee osteoarthritis (OA). DESIGN: A double-blind, randomized, placebo-controlled
      study. SETTING: Rehabilitation clinic. PARTICIPANTS: Women (n=62) and men (n=10)
      with a mean age of 61.2 years (range, 40-88y). All patients fulfilled the
      combined clinical and radiographic criteria for knee OA as established by the
      American College of Rheumatology, and all had obtained a Kellgren-Lawrence score
      of 2 or more. INTERVENTIONS: Participants received 6 sessions, lasting 40 minutes
      each, of active or placebo radiation treatment over the knee joints for 2 weeks
      (wavelength, 890nm; radiant power output, 6.24W; power density, 34.7mW/cm(2) for
      40 minutes; total energy, 41.6J/cm(2) per knee per session). MAIN OUTCOME
      MEASURES: Participants were assessed weekly over 4 weeks using the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain,
      stiffness, and physical function. Physical activity (timed stair climbing, 10-m
      fast-speed walking, and chair-rising time) and postural stability (using the
      postural stability evaluation system) were also assessed. The pain score on WOMAC
      was the primary outcome variable. Data were analyzed by repeated-measures
      analysis of covariance. RESULTS: Compared with baseline, no significant
      improvement was observed between groups for pain (P=.546), stiffness (P=.573), or
      physical function (P=.904). No significant improvement was noted for physical
      activity including the 10-m fast-speed walking time (P=.284), stair-climbing time
      (P=.202), stair-descending time (P=.468), chair-rising time (P=.499), or postural
      stability (P=.986) at the 4 follow-up assessments. Follow-up assessments were
      conducted after 1 week of treatment (thus, after 3 treatments); after 2 weeks of
      treatment (thus, after 6 treatments); and 1 and 2 weeks, respectively, after
      treatment was terminated. Although we found a significant time effect for the 10
      m fast-speed walking time (P<.001) in the 2 groups, and a significant group
      effect in the improvement of stair-climbing time in the treatment group (P=.032),
      the group * time interaction effects were not significant. CONCLUSIONS: Short
      term 890-nm radiation therapy for patients with knee OA provided no beneficial
      effect in improving pain, physical activity, and postural stability.

PMID- 22459701
TI  - Predict mycobacterial proteins subcellular locations by incorporating pseudo
      average chemical shift into the general form of Chou's pseudo amino acid
      composition.
AB  - Mycobacterium tuberculosis (MTB) is a pathogenic bacterial species in the genus
      Mycobacterium and the causative agent of most cases of tuberculosis (Berman et
      al., 2000). Knowledge of the localization of Mycobacterial protein may help
      unravel the normal function of this protein. Automated prediction of
      Mycobacterial protein subcellular localization is an important tool for genome
      annotation and drug discovery. In this work, a benchmark data set with 638 non
      redundant mycobacterial proteins is constructed and an approach for predicting
      Mycobacterium subcellular localization is proposed by combining amino acid
      composition, dipeptide composition, reduced physicochemical property,
      evolutionary information, pseudo-average chemical shift. The overall prediction
      accuracy is 87.77% for Mycobacterial subcellular localizations and 85.03% for
      three membrane protein types in Integral membranes using the algorithm of
      increment of diversity combined with support vector machine. The performance of
      pseudo-average chemical shift is excellent. In order to check the performance of
      our method, the data set constructed by Rashid was also predicted and the
      accuracy of 98.12% was obtained. This indicates that our approach was better than
      other existing methods in literature.

PMID- 22459702
TI  - Origins of evolution: non-acquired characters dominates over acquired characters
      in changing environment.
AB  - Natural Selection is so ubiquitous that we never wonder how it appeared as the
      evolution rule driving Life. We usually wonder how Life appeared, and seldom do
      we make an explicit distinction between Life and natural selection. Here, we
      apply the evolution concept commonly used for studying Life to evolution itself.
      More precisely, we developed two models aiming at selecting among different
      evolution rules competing for their supremacy. We explored competition between
      acquired (AQ) versus non-acquired (NAQ) character inheritance. The first model is
      parsimonious and non-spatial, in order to understand relationships between
      environmental forcings and rule selection. The second model is spatially explicit
      and studies the adaptation differences between AQ and NAQ populations. We
      established that NAQ evolution rule is dominating in case of changing
      environment. Furthermore, we observed that a more adapted population better fits
      its environmental constraints, but fails in rapidly changing environments. NAQ
      principle and less adapted populations indeed act as a reservoir of traits that
      helps populations to survive in rapidly changing environments, such as the ones
      that probably Life experienced at its origins. Although perfectible, our modeling
      approaches will certainly help us to improve our understanding of origins of Life
      and Evolution, on Earth or elsewhere.

PMID- 22459703
TI  - Oscillations in glycolysis in Saccharomyces cerevisiae: the role of autocatalysis
      and intracellular ATPase activity.
AB  - We have investigated the glycolytic oscillations, measured as NADH
      autofluorescence, in the yeast Saccharomyces cerevisiae in a batch reactor.
      Specifically, we have tested the effect of cell density and a number of
      inhibitors or activators of ATPase activity on the amplitude of the oscillations.
      The amplitude dependence on cell density shows the same behavior as that observed
      in cells in a CSTR. Furthermore, the amplitude decreases with increasing
      inhibition of the three ATPases (i) F(0)F(1) ATPase, (ii) plasma membrane ATPase
      (Pma1p) and (iii) vacuolar ATPase (V-ATPase). The amplitude of the oscillations
      also decreases by stimulating the ATPase activity, e.g. by FCCP or Amphotericin
      B. Thus, ATPase activity strongly affects the glycolytic oscillations. We discuss
      these data in relation to a simple autocatalytic model of glycolysis which can
      reproduce the experimental data and explain the role of membrane-bound ATPases .
      In addition we also studied a recent detailed model of glycolysis and found that,
      although this model faithfully reproduces the oscillations of glycolytic
      intermediates observed experimentally, it is not able to explain the role of
      ATPase activity on the oscillations.

PMID- 22459704
TI  - Biological properties and regulation of IL-10 related cytokines and their
      contribution to autoimmune disease and tissue injury.
AB  - The IL-10 cytokine family has nine members, four of which are located in the IL10
      cluster on chromosome 1q32. These cytokines are the immune regulatory cytokine IL
      10 itself, and the IL-20 subfamily members IL-19, IL-20, and IL-24. IL-10
      instructs innate and adaptive immune responses and limits pro-inflammatory
      responses in order to prevent tissue damage. The IL-20 subfamily members are
      involved in host defense mechanisms, particularly from epithelial cells and seem
      essential for tissue integrity. Dysregulation of IL-10 family cytokines results
      in inflammation and autoimmune disease. Here, we discuss cellular source, gene
      regulation, and receptor complexes of cytokines in the IL10 cluster and their
      contribution to autoimmune disease and tissue damage.

PMID- 22459705
TI  - CD40 agonist antibody mediated improvement of chronic Cryptosporidium infection
      in patients with X-linked hyper IgM syndrome.
AB  - X-linked hyper-IgM syndrome (XHM) is a combined immune deficiency disorder caused
      by mutations in CD40 ligand. We tested CP-870,893, a human CD40 agonist
      monoclonal antibody, in the treatment of two XHM patients with biliary
      Cryptosporidiosis. CP-870,893 activated B cells and APCs in vitro, restoring
      class switch recombination in XHM B cells and inducing cytokine secretion by
      monocytes. CP-870,893 infusions were well tolerated and showed significant
      activity in vivo, decreasing leukocyte concentration in peripheral blood.
      Although specific antibody responses were lacking, frequent dosing in one subject
      primed T cells to secrete IFN-g and suppressed oocyst shedding in the stool.
      Nevertheless, relapse occurred after discontinuation of therapy. The CD40
      receptor was rapidly internalized following binding with CP-870,893, potentially
      explaining the limited capacity of CP-870,893 to mediate immune reconstitution.
      This study demonstrates that CP-870,893 suppressed oocysts shedding in XHM
      patients with biliary cryptosporidiosis. The continued study of CD40 agonists in
      XHM is warranted.

PMID- 22459706
TI  - Program death-1 regulates peripheral T cell tolerance via an anergy-independent
      mechanism.
AB  - Program death-1 (PD-1) has been documented to negatively regulate immune
      responses. However, the cellular and molecular mechanisms for PD-1-mediated
      immune suppression have not been fully elucidated. In this study, we show that
      loss of PD-1 does not lead to defective induction of CD4(+) T cell anergy in
      vitro and in vivo. Rather, the absence of PD-1 inhibits the development of
      inducible CD4(+)Foxp3(+) regulatory T cells (iTregs) induced by TGF-beta in
      vitro. In support of this finding, PD-1 deficiency impairs the generation of
      iTregs in vivo and leads to development of severe T cell-transfer-induced
      colitis. Mechanistically, defective iTreg generation in the absence of PD-1 was
      attributed to the heightened phosphorylation of Akt. Therefore, we first
      demonstrate that PD-1 controls peripheral T cell tolerance via an anergy
      independent but iTreg-dependent mechanism.

PMID- 22459707
TI  - Childbearing history and late-life mortality: the Dubbo study of Australian
      elderly.
AB  - OBJECTIVE: to examine the association of parity with mortality in later life.
      DESIGN: a longitudinal, community-based study. SETTING: semi-rural town of Dubbo,
      NSW, Australia. SUBJECTS: a total of 1,571 women and 1,233 men 60 years and older
      first examined in 1988-89. OUTCOME MEASURES: all-cause and cause-specific
      mortality rates analysed over 16-year follow-up. Hazard ratios obtained from
      proportional hazards models employing conventional predictors, potential
      confounders and measure of parity. RESULTS: increasing parity in women was weakly
      associated with overweight, diabetes and hypertension. All-cause mortality fell
      progressively with increasing parity in women (hazard ratio and 95% confidence
      intervals): childless, 1.00; 1 child, 1.03 (0.75-1.43); 2 children, 0.83 (0.61
      1.11); 3 children, 0.80 (0.60-1.08); 4 children, 0.91 (0.66-1.25); 5 children,
      0.70 (0.49-1.01); 6+ children, 0.60 (0.43-0.85) (trend for parity P<0.002). This
      result was similar whether or not hypertension, diabetes and overweight were
      included in multivariate models adjusting for social variables and other
      confounders. The reduction in all-cause mortality was accompanied by a parallel
      reduction in deaths from cancer and respiratory conditions, while coronary heart
      disease mortality increased 60-111% in all parous women. CONCLUSION: there was
      increased all-cause mortality in later life in childless women, accompanied by
      reduced mortality as parity increased. Underlying mechanisms are unclear but
      findings may have public health importance.

PMID- 22459709
TI  - Release of native and mass labelled PCDD/PCDF from soil heated to simulate
      bushfires.
AB  - Soil is an important reservoir of PCDD/PCDF, which can be released when
      environmental conditions change. Fire is an extreme event that can increase the
      surface temperatures of soil substantially, yet little is known of the role soil
      plays in the emission of PCDD/PCDF. Soil containing native PCDD/PCDF was
      fortified with a mixture of mass labelled PCDD/PCDF and heated between 150 
      degrees C and 400  degrees C. Both native and mass labelled PCDD/PCDF were
      released from the soil beyond 200  degrees C. Release of the mass labelled
      compounds was linearly related to temperature with up to 9 % found in the air
      stream at 400  degrees C. The release of some native PCDD/PCDF was much greater.
      At 400  degrees C, emission of 1,2,3,7,8-Cl(5)DD was 300% compared to pre
      experimental soil. Emission of PCDD/PCDF from soil during bushfires is a relevant
      process and may originate from both volatilization and formation via de novo or
      precursor pathways, or dechlorination.

PMID- 22459708
TI  - Country-specific correlations across Europe between modelled atmospheric cadmium
      and lead deposition and concentrations in mosses.
AB  - Previous analyses at the European scale have shown that cadmium and lead
      concentrations in mosses are primarily determined by the total deposition of
      these metals. Further analyses in the current study show that Spearman rank
      correlations between the concentration in mosses and the deposition modelled by
      the European Monitoring and Evaluation Programme (EMEP) are country and metal
      specific. Significant positive correlations were found for about two thirds or
      more of the participating countries in 1990, 1995, 2000 and 2005 (except for Cd
      in 1990). Correlations were often not significant and sometimes negative in
      countries where mosses were only sampled in a relatively small number of EMEP
      grids. Correlations frequently improved when only data for EMEP grids with at
      least three moss sampling sites per grid were included. It was concluded that
      spatial patterns and temporal trends agree reasonably well between lead and
      cadmium concentrations in mosses and modelled atmospheric deposition.

PMID- 22459710
TI  - Multicorrelation models and uptake factors to estimate extractable metal
      concentrations from soil and metal in plants in pasturelands fertilized with
      manure.
AB  - Environmental risk assessment (ERA) is a useful methodology to estimate the
      possible adverse effects to human health due to contaminants exposure. In the
      case of agricultural scenarios, this method requires knowing the concentrations
      of contaminants in soil solution and vegetation, among other parameters. This
      study aimed to develop multicorrelation models to estimate metal extractable from
      soil as a function of total metal concentration in soil and soil properties in a
      cattle manure application scenario. It also aimed to estimate metal
      concentrations in plant by soil-plant uptake factors (UF). All the
      multicorrelation models obtained were significant, ranging R(2) values from 0.44
      for Cd to 0.92 for Cu. Soil-plant UF were an adequate method for the estimation
      of metal concentration in plant, since the relationship between the soil-plant UF
      and the extractable metal concentration from soil was significantly described by
      a power model, for all the heavy metals.

PMID- 22459711
TI  - A geochemical study of toxic metal translocation in an urban brownfield wetland.
AB  - Rhizosphere soil and dominant plant samples were collected at a brownfield site
      in New Jersey, USA, during summer 2005 to evaluate plant metal uptake from the
      contaminated soils. Metal concentrations varied from 4.25 to 978 MUg g(-1) for
      As, 9.68-209 MUg g(-1) for Cr, 23.9-1870 MUg g(-1) for Cu, and 24.8-6502 MUg g(
      1) for Zn. A wide range of metal uptake efficiencies in the roots, stems and
      leaves was found in this study. Data showed that (1) Betula populifolia has high
      Zn, Cu and As accumulations in the root, and high concentrations of Cu and Zn in
      the stem and the leaf; (2) Rhus copallinum has high accumulation of Zn and Cr in
      the leaf and Cu in the stem; (3) Polygonum cuspidatum has high accumulations of
      Cu and As in the root; and (4) Artemisia vulgaris shows high Cu accumulation in
      the leaf and the stem.

PMID- 22459713
TI  - Substantial need for early diagnosis, rehabilitation and treatment of chronic
      obstructive pulmonary disease.
AB  - INTRODUCTION: Our goal was to estimate the number of individuals with chronic
      obstructive pulmonary disease (COPD) in the Capital Region of Denmark and the
      need of resources required to implement the regional management programme for
      COPD. MATERIAL AND METHODS: We examined a total of 45,970 participants from the
      Copenhagen General Population Study (CGPS) using spirometry and a questionnaire.
      RESULTS: The prevalence of spirometrically defined COPD among individuals older
      than 40 years of age was 15%, corresponding to 120,000 citizens in the Region.
      The number of individuals with moderate COPD (forced expiratory volume in one
      second (FEV1): 50-80% of predicted value) was estimated to approx. 51,000 (6.4%),
      whereas at least 10,000 (1.3%) were expected to have severe or very severe COPD
      (FEV1 < 50% of predicted value). Our estimates indicate that more than 26,000
      individuals with moderate, severe or very severe COPD in the Region are smokers
      and that more than 19,000 qualify for physical training. We estimated that
      approx. 4,000 individuals with severe COPD were not treated with any inhaled
      medication. CONCLUSION: The Capital Region of Denmark needs to allocate
      substantial resources into early detection, rehabilitation and medical treatment
      of individuals with COPD in order to comply with the intentions of the Region's
      own management programme for COPD. FUNDING: The present analyses were sponsored
      by a grant from the Danish Ministry of Health. The CGPS was supported by the
      Copenhagen County Foundation, the Danish Medical Research Council and the Boserup
      Foundation. TRIAL REGISTRATION: not relevant.

PMID- 22459714
TI  - Fast track accelerated diagnostic investigation for urinary incontinence in
      women.
AB  - INTRODUCTION: We have developed a one-hour standardised, accelerated diagnostic
      investigation programme to evaluate women with urinary incontinence (UI). The
      purpose of the study was to record how many patients followed the programme and
      had a diagnosis and a treatment plan after a one-hour visit and to describe the
      causes of deviation from the programme. A second purpose was to monitor patient
      satisfaction. METHODS: In this retrospective cohort study, 276 women with the
      diagnosis UI participated. All patients completed a standardised investigation
      programme that included their medical history and an evaluation of the
      fluid/urination schedule. Before patients left the clinic, they were given a
      diagnosis and a treatment plan. RESULTS: A total of 91% of the patients underwent
      examination and had a treatment plan after one consultation; 9% made multiple
      visits. The median patient age was 59 years (range 17-99 years); body mass index
      was 27 kg/m2 (range 18-50 kg/m2); and the number of childbirths was 2.4; no
      significant difference were observed between the two groups. In the multiple
      visits group, the number of previous gynaecological surgical procedures was
      significantly larger (67% versus 32%). These patients had significantly more
      chronic diseases (88% versus 58%). A total of 81 patients completed a post
      examination questionnaire and (99%) were satisfied with the accelerated
      programme. CONCLUSION: A total of 91% of the patients underwent an examination
      and received a treatment plan after one consultation; 9% paid several visits due
      to chronic diseases and previous gynaecological surgery. The patients expressed
      great satisfaction with the accelerated investigation programme. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 22459715
TI  - Need for improved treatment of postoperative pain.
AB  - INTRODUCTION: A cross-sectional study was performed at Rigshospitalet,
      Copenhagen, a Danish tertiary university hospital, to describe current
      postoperative pain and nausea treatment with a view to identifying areas with
      improvement potential. MATERIAL AND METHODS: Data on up to four of the major and
      most frequent types of surgery were collected from each department based on
      interviews with the staff, audits of patient courses and electronic patient
      medication records. Staff guidelines on procedure-specific pain treatment were
      also collected. RESULTS: Data on 121 patients from 12 surgical departments and 44
      procedures were included in the study. No reliable information about the quality
      of pain management was available as no data on pain scores were detectable for
      the first three postoperative days (POD) for 55% (day 1), 71% (day 2) and 84%
      (day 3) of the patients. Most patients (75%) were treated with opioids. Non
      opioid analgesic treatment was insufficient as the majority of patients did not
      receive sufficient 24-hour treatment with paracetamol and non-steroidal anti
      inflammatory drugs, and only a minority received combination therapy. Nausea was
      found in approx. 20% on POD 1-3. Staff pain treatment guidelines were present in
      14% of the cases. CONCLUSION: Our results confirm that challenges exist in
      postoperative pain management as previously observed in multinational surveys.
      The way forward is procedure-specific treatment plans based on interdisciplinary
      collaboration implemented in conjunction with organizational changes. This work
      represents a natural extension of the work of the traditional acute pain clinic.
      FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22459716
TI  - High prevalence of asthma in Danish elite canoe- and kayak athletes.
AB  - INTRODUCTION: Asthma is common in elite athletes, but our knowledge of asthma in
      elite canoe and kayak athletes is limited. The aim of the present prospective
      cross-sectional study was therefore to investigate the prevalence of asthma,
      including asthma-like symptoms, exhaled nitric oxide, and airway reactivity to
      mannitol in Danish elite canoe and kayak athletes MATERIAL AND METHODS: The study
      group consisted of 29 (of 33 eligible) elite athletes aged 17-43 years, and the
      examination programme consisted of questionnaires, including the Asthma Control
      Questionnaire, fraction of exhaled nitric oxide (FENO), spirometry and airway
      reactivity to mannitol. Asthma was defined as a history of doctor-diagnosed
      asthma and/or elevated FENO and airway reactivity. RESULTS: Seven of the elite
      athletes (24.1%) were found to have asthma, including four subjects with
      previously doctor-diagnosed asthma. Of the four athletes (all treated with
      inhaled corticosteroids) with doctor-diagnosed asthma, all reported asthma
      symptoms and two had elevated FENO, but none had airway hyperresponsiveness (AHR)
      to mannitol. All three athletes with previously undiagnosed asthma had elevated
      FENO and AHR to mannitol, but reported no asthma-like symptoms. CONCLUSION:
      Asthma is common in elite canoe and kayak athletes, and classical signs of
      asthmatic airway inflammation are also found in asymptomatic athletes. FUNDING:
      not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22459717
TI  - Only few severe complications after endoscopic ultrasound guided drainage of
      pancreatic pseudocysts.
AB  - INTRODUCTION: Pancreatic pseudocysts arise as a complication to acute or chronic
      pancreatitis. Transmural drainage under guidance of endoscopic ultrasound (EUS)
      is a minimally invasive approach. The results of a case series was
      retrospectively reviewed with a mean follow-up of 441 days. MATERIAL AND METHODS:
      Twenty-two consecutive patients (mean age 51 years, 13 men) who had undergone EUS
      guided drainage of pancreatic pseudocysts were included between December 2005 and
      August 2010. The mean cyst size was 8.1 cm. One or two 10 Fr. double pigtail
      stents were inserted into the pseudocyst from either the stomach or the duodenum.
      RESULTS: Insertion of a stent failed in three of 22 patients. Two cases were
      discontinued due to technical difficulties. One procedure was converted to a
      surgical cystogastrostomy. In 19 patients, a stent was successfully inserted.
      Three developed symptomatic recurrences due to stent malfunction. One developed a
      pseudocyst that mechanically obstructed the common bile duct. One developed a
      malignant cyst. One had a surgical cystogastrostomy for reasons unrelated to the
      stent insertion. For 13 patients (59%), a single endoscopic treatment resulted in
      relief of symptoms and resolution of the pseudocysts. However, one of these
      subsequently developed an asymptomatic pseudocyst. CONCLUSION: EUS-guided
      endoscopy has only few severe complications and long-term results are acceptable.
      Nevertheless, insertion can be technically challenging and stent-related
      complications may cause recurrence. FUNDING: not relevant. TRIAL REGISTRATION:
      not relevant.

PMID- 22459718
TI  - Low confidence among general practitioners in end-of-life care and subcutaneous
      administration of medicine.
AB  - INTRODUCTION: Most terminally ill patients prefer to die at home, and the general
      practitioner (GP) is central in making this possible. However, knowledge is
      needed about the GP's level of confidence in assuming this task and with
      subcutaneous (SC) administration of medicine in end-of-life care. The aim of this
      study was to determine if GPs used SC needle and medication in end-of-life care,
      if they felt confident about being principally responsible for palliative
      trajectories and whether such confidence was associated with GP characteristics.
      MATERIAL AND METHODS: This was a cross-sectional questionnaire survey of all 332
      GPs practising in Copenhagen, Denmark. Questions covered the GPs' use of SC
      medication/needle and their confidence in being principally responsible for
      palliative trajectories. RESULTS: The survey response rate was 61%. 43% of the
      respondents had been principally responsible for a minimum of one palliative
      trajectory, and only 11% of these GPs had used a SC needle during this process.
      57% felt very or somewhat confident being principally responsible and 27% felt
      very or somewhat confident administrating SC medicine. Confidence as principally
      responsible was positively associated with the number of palliative trajectories
      for which the GP had been responsible, but no significant associations with the
      GPs' age, gender or practice organisation were found. CONCLUSION: We found that
      few GPs in Copenhagen feel very confident about being responsible for terminal
      care and that very few used SC needles. Hence, more education and training in
      this field is warranted. Further research is needed into how GPs may best become
      involved and supported in end-of-life care. FUNDING: Danish General
      Practitioners' Educational and Development Fund. TRIAL REGISTRATION: not
      relevant.

PMID- 22459719
TI  - Acceptable results after venous reconstructive surgery following iatrogenic
      injuries to the iliofemoral vein segment.
AB  - INTRODUCTION: Venous reconstructions after iatrogenic injuries are rarely
      performed and are associated with a relatively high risk of complications. We
      present our experiences with venous reconstructive surgery to the iliofemoral
      vein segment. MATERIAL AND METHODS: We reviewed ten patients with venous injuries
      evaluating clinical characteristics, operative and postoperative data including
      location and type of venous injury, operative repair and outcome. Venous injuries
      either occurred during varicose vein surgery or other kinds of procedures in the
      region. The injuries were repaired by interposition with a polytetrafluorethylene
      graft, and after surgery they were treated with an intermittent pneumatic
      compression device and anticoagulation medicine. Subsequently, patients were
      evaluated both clinically and by colour duplex scan. RESULTS: The mean patient
      age was 42.5 years (range 26-61 years) with no reported co-morbidity. The median
      follow-up was 16 months (range 12-157 months). The 30-day patency rate was 70%
      and the morbidity rate 40%. At the latest follow-up, the venous patency rate was
      90% after supplementary treatment. CONCLUSION: The study shows a satisfactory
      outcome despite severe iatrogenic injuries to the iliofemoral vein segment.
      Venous reconstructive surgery should be a centralized task. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 22459720
TI  - Large discrepancy between prehospital visitation to mobile emergency care unit
      and discharge diagnosis.
AB  - INTRODUCTION: In Copenhagen, Denmark, patients in need of prehospital emergency
      assistance dial 112 and may then receive evaluation and treatment by physicians
      (from the Mobile Emergency Care Unit (MECU)). ST-elevation myocardial infarction
      (STEMI) is a severe condition leaving only a limited time frame to deliver
      optimal care in the form of percutaneous transluminal coronary angioplasty. In
      theory, all patients with chest pain could have STEMI. The aim of this study was
      to study which of the patients suspected of having acute cardiac disease based on
      the 112 calls and met by the MECU were given a cardiac diagnosis on the scene
      and, furthermore, to compare these on-scene diagnoses with the primary discharge
      diagnoses from hospital. MATERIAL AND METHODS: This was a retrospective study
      based on medical records from the MECU and the National Patient Registry. The
      study period covered six months in 2008 during which all 112-alarms to acute
      cardiac disease cases were met by the MECU were included. The study population
      comprised 1,219 patients. RESULTS: A total of 780 (66.3%) of the dispatches
      resulted in a cardiac diagnosis by the MECU physician. 77% of the admitted
      patients were diagnosed with a primary cardiac disease on discharge. These were
      categorized into three groups: acute coronary syndrome (314 patients, 57%),
      cardiac arrhythmias (58 patients, 10%), and other cardiac disorders (183
      patients, 33%). Only 46% of the study population was discharged from hospital
      with a cardiac diagnosis CONCLUSION: Only half of the included patients were
      discharged from hospital with a cardiac diagnosis, which leaves room for
      improvement. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 22459721
TI  - No effect of corticosteroid treatment for idiopathic facial paralysis.
AB  - INTRODUCTION: This retrospective cohort study aimed to determine if the effect of
      corticosteroid treatment on idiopathic facial palsy (IFP) could be reproduced in
      patients treated in a strictly clinical setting. MATERIAL AND METHODS: A total of
      43 patients diagnosed with IFP in the period 2004-2009 were included and patient
      files were reviewed. Treatment with corticosteroids was introduced as standard
      treatment for this disease in December 2006, ensuring groups of similar size. In
      all, 20 patients had received prednisolone and 23 patients had not. Baseline
      characteristics were registered and severity of facial palsy according to the
      House-Brackmann grading system (HB) was determined before treatment and at follow
      up. RESULTS: Change in HB score did not differ between participant groups (delta
      HB: 3 (range: 0-5), and 3 (range: 1-5), patients treated with steroids versus
      patients receiving no treatment, respectively, p = 0.69). When dividing patients
      into sub-groups according to age (age >/<= 40 years), no difference was found for
      change in HB score between treatment groups for either age group (age <= 40
      years; p = 0.59, and age > 40 years; p = 0.12). The effect of steroid treatment
      on outcome was larger among older than among younger patients (p = 0.03).
      CONCLUSION: Treatment with prednisolone does not improve short-term outcome in
      patients with IFP in an unselected clinical setting. Further studies should
      evaluate the possible effect of age on treatment outcome. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant.

PMID- 22459722
TI  - Prehospital guidelines for use of hypertonic saline are not followed
      systematically.
AB  - INTRODUCTION: Hypertonic saline (HS) was introduced in our physician-based mobile
      emergency care unit (MECU) in September 2006 for patients with severe traumatic
      brain injury and hypotension. HS has, however, rarely been used and we sought to
      identify barriers to its implementation. MATERIAL AND METHODS: We conducted a
      survey based on a questionnaire administered to all 40 anaesthesiologists
      employed at the MECU in Copenhagen as per August 2010. RESULTS: A total of 31
      anaesthesiologists (84%) returned the questionnaire. Three physicians were
      excluded because of leave. Almost half of the physicians considered the evidence
      for use of HS insufficient, and 29% found that guidelines were lacking.
      Noticeable barriers were inadequate familiarity with and unawareness of the
      guideline. Some believed that they may have failed to use HS because the option
      did not occur to them during the relevant incidents. Many physicians stated that
      training at the MECU should be more thorough and that instructions were missing.
      CONCLUSION: Barriers to the implementation of HS were lack of familiarity with
      the guideline and disagreement regarding the evidence supporting its use.
      Possible solutions to these implementation issues include additional instructions
      and internal MECU meetings FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 22459723
TI  - Functional and immunological analysis of the human sperm proteome.
AB  - This is a review of ten previously published studies of the human sperm proteome.
      Proteins expressed on the sperm cell surface were identified and characterized by
      a combination of vectorial labelling with radioiodine and biotin, PI-PLC
      treatment, two-dimensional gel electrophoresis, immuno and lectin blotting
      procedures, affinity overlay assays with radioactive nucleotide triphosphates and
      45Ca, and mass spectrometry analysis.  Examination of capacitation-induced
      modifications of the human sperm proteome led to the cloning and characterisation
      of two new phospho-regulated cancer-testis antigens, which we named Fibrous
      Sheath Protein 95 (FSP95) and CABYR (calcium-binding tyrosine phosphorylation
      regulated).   A protein kinase A RII binding domain is present between amino
      acids 124 and 141 identifying FSP95 (now commonly known as AKAP3) as a member of
      the A kinase anchoring protein-family which provides spatial and temporal
      specificity to the cAMP-PKA pathway. In addition to scaffolding PKA, PDE and
      protein phosphatases, AKAPs also bind to a group of four proteins that share
      homology to the RII dimerization/docking (R2D2) domain of PKA' regulatory
      subunit.  CABYR, which is one of these four proteins, also interacts with a
      diverse array of signal tranducers via its SH3-, R2D2-, and proline-rich
      extension-like domains. AKAP3 and CABYR appear to associate in high molecular
      weight multi-protein complexes, which regulate the flagella' energy supply and
      movements. Diagonal gel electrophoresis experiments suggest that the high
      molecular weight signal-integrating scaffold partly is established by homo- and
      hetero-oligomerization of lower molecular weight splice variants of CABYR. The
      putative role of CABYR in lung cancer cells is finally discussed.

PMID- 22459724
TI  - The effect of selective serotonin reuptake inhibitors in healthy first-degree
      relatives of patients with major depressive disorder - an experimental medicine
      blinded controlled trial.
AB  - The mechanisms of action for selective serotonin re-uptake in-hibitors (SSRI) in
      depressed patients remain widely unknown. The serotonergic neurotransmitter
      system and the hypothalamic-pituitary-adrenal (HPA) system may interact. Further,
      the serotonergic neurotransmitter system seems closely linked to personality and
      cognition. It is not known if SSRIs have a direct effect on the HPA system,
      personality or cognition that is independent of their effect on depression. Thus,
      healthy individuals with a genetic liability for depression represent a group of
      particular interest when investigating if intervention with SSRIs affects these
      potential biomarkers. SSRIs may affect these potential biomarkers in depressed
      patients, but it is unclear if the effect is directly on the biomarkers or is
      secondary to the effect of SSRIs on depressive symptoms. It has newer been tested
      whether an intervention with a SSRI has a beneficial effect on these potential
      biomarkers in healthy individuals with a genetic liability for depression. The
      aim of the thesis was by an experimental medicine blinded controlled trial, to
      investigate if long-term intervention with SSRI versus placebo decreases cortisol
      response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in
      healthy first-degree relatives to patients with major depressive disorder (MDD).
      Further, to test the hypothesis that a SSRI may reduce neuroticism in healthy
      first-degree relatives of patients with MDD. Finally, to test whether SSRI
      enhance cognitive function in healthy first-degree relatives of patients with
      MDD. Eighty healthy first-degree relatives to patients with MDD were randomised
      to receive escitalopram 10 mg versus matching pla-cebo daily for four weeks in a
      blinded trial. The primary outcome measure was the intervention difference in the
      change of the total area under the curve (CorAUCtotal) for plasma cortisol in the
      DEX-CRH test at entry to after four weeks of intervention. The secondary outcomes
      were a) change in self-reported neuroticism scores on the 240-items Revised
      Neuroticism-Extroversion-Openness-Personality Inventory (NEO-PI-R) and the 101
      items Eysenck Personality Inventory (EPQ) at entry to after four weeks of
      intervention and b) the change in the general cognition score, which was the
      standardised mean of 13 cognitive test measures. Change in CorAUCtotal showed no
      statically significant difference between the escitalopram and the placebo group,
      p = 0.47. Fur-ther, escitalopram did not significantly affect self-reported neu
      roticism compared with placebo, NEO-PI-R (p = 0.09) and EPQ (p = 0.73). Finally,
      mean change in the general cognition score was not significantly increased with
      escitalopram compared with placebo, (p = 0.37). In univariate analyses, no
      statistically significant correlations were found between change in the primary
      and secondary outcomes, respectively, and the covariates age, sex, Hamilton
      depression score 17-items, and plasma escitalopram levels. In conclusion, the
      present trial does not support an effect of escitalopram 10 mg daily compared
      with placebo on the HPA-axis, neuroticism and cognitive function in healthy first
      degree relatives to patients with MDD.

PMID- 22459725
TI  - Communication among neurons.
AB  - The communication among neurons is the prerequisite for the working brain. To
      understand the cellular, neurochemical, and structural basis of this
      communication, and the impacts of aging and disease on brain function,
      quantitative measures are necessary. This thesis evaluates several quantitative
      neurobiological methods with respect to possible bias and methodological issues. 
      Stereological methods are suited for the unbiased estimation of number, length,
      and volumes of components of the nervous system. Stereological estimates of the
      total length of myelinated nerve fibers were made in white matter of post mortem
      brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's
      disease were evaluated. Although stereological methods are in principle unbiased,
      shrinkage artifacts are difficult to account for.   Positron emission tomography
      (PET) recordings, in conjunction with kinetic modeling, permit the quantitation
      of radioligand binding in brain. The novel serotonin 5-HT4 antagonist
      [11C]SB207145 was used as an example of the validation process for quantitative
      PET receptor imaging. Methods based on reference tissue as well as methods based
      on an arterial plasma input function were evaluated with respect to precision and
      accuracy. It was shown that [11C]SB207145 binding had high sensitivity to
      occupancy by unlabeled ligand, necessitating high specific activity in the
      radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand
      [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects.
      Application of partial volume correction of the PET data diminished the
      reliability of the measures, but allowed for the correct distinction between
      changes due to brain atrophy and receptor availability. Furthermore, a PET study
      of patients with Alzheimer's disease with the serotonin transporter ligand
      [11C]DASB showed relatively preserved serotonergic projections, despite a marked
      decrease in 5-HT2A receptor binding. Possible confounders are considered and the
      relation to the prevailing beta-amyloid hypothesis is discussed.

PMID- 22459726
TI  - Aspects of survival from colorectal cancer in Denmark.
AB  - This thesis has reported survival among Danish colorectal cancer patients over
      the past decades and it has explored different aspects of the inferior short-term
      and long-term survival of Danish patients in relation to (i) patient factors: old
      age and comorbidity; (ii) disease factors: prognostic factors for early death
      after emergency surgery; (iii) diagnostic factors: impact of diagnostic delay;
      (iv) treatment factors: seasonal variation in postoperative mortality and the
      benefit of a new approach for management of obstructive cancer; and (v)
      structural factors: hospital volume and surgeon characteristics. Short-term
      survival. For colonic cancer, the 30-day relative survival rose from 86% in 1977
      1982 to 90% in 1995-1999, and for rectal cancer it rose from 90% to 94% (I). Data
      from regional hospital discharge registries show that the overall 30-day
      mortality rates of colonic and rectal cancer remained stable at about 11% and 4
      5%, respectively, during 1985-2004 (II). Stratifying for urgency of surgery, but
      not for tumour site, the 30-day mortality rate was 6.2% after elective surgery
      and 22.1% after emergency surgery in the period 2001-2008 according to DCCG data
      (17). Nevertheless, the 30-day mortality was about twice as high in Denmark as in
      Norway, Sweden and Scotland, even if the data for these countries are older than
      the Danish data. Mortality rates after palliative surgery are three times higher
      than the rates following curative surgery (115). The stage distribution at the
      time of diagnosis is more unfavourable in Denmark than in the other Nordic
      countries (114). Comparison of survival among countries is, however, encumbered
      by several methodological issues related to completeness, and data quality of
      cancer registries, among others, biases the survival estimates. Like most western
      populations, the Danish population is ageing and the proportion of elderly
      colorectal cancer patients aged >75 years has therefore risen from 37% in 1977
      1982 to 42% in 1995-1999 (III). Disparity in cancer treatment between elderly and
      younger patients exists on a number of counts, e.g., the former's curative
      resection rate is lower, their emergency presentation rate is higher and they are
      moreover more likely to present with later-stage disease than are younger
      patients. However, in Denmark the curative resection rate among elderly patients
      aged >75 years rose from 36% in 1977-1982 to 49% in 1995-1999 (III). This trend
      was paralleled by an increase in 30-day and 6-month relative survival. Patients
      aged >70 years have a 30-day mortality rate of 13.1%, but their younger
      counterparts' mortality rate is only 3.5% (17). A mortality rate at least two to
      three times higher among the elderly than among younger patients has been
      reported repeatedly in various populations
      (95,96,116,127,128,130,131,135,136,144,145). In Denmark there is an inverse
      relationship between the comorbidity level and the resection rate in colorectal
      cancer. In the period 1995-2006, surgical treatment of patients with colonic
      cancer and severe comorbidity became progressively more aggressive, whereas
      surgical treatment of patients with rectal cancer apparently became more cautious
      or differentiated (VI). Nevertheless, the overall 30-day mortality rate after
      resectional surgery remained stable at about 8% in colonic cancer and at about 6%
      in rectal cancer. Almost every fourth patient had severe comorbidity as
      determined by an ASA of III or more and their 30-day mortality rate was at least
      18% in 2001-2008. Any reduction in their short-term mortality will therefore have
      a substantial impact on the overall mortality rate. Despite the impact of
      comorbidity on postoperative mortality, the distinct seasonal variation seen in
      mortality from cardiovascular and respiratory diseases, with excess mortality in
      the winter months, has not been observed in postoperative mortality from
      colorectal cancer (VII). Postoperative mortality from colonic cancer was non
      significantly higher in July than in other months of the year (VII). Evidence
      reveals a volume-outcome relationship regarding postoperative mortality in
      colonic cancer (IV) and the most recent literature suggests that it probably also
      is so in rectal cancer. However, volume may be a surrogate marker or proxy for
      other important structural factors such as quality and capacity of intensive care
      units, the availability of other clinical services like cardiac care units,
      multiple medical specialties, multidisciplinary infrastructure and nurse
      staffing, etc. Postoperative mortality after emergency surgery for colonic cancer
      was as high as 22% in 2001-2005 and mortality was significantly associated with
      the postoperative course. Patients developing medical complications had a
      mortality rate of 57.8%. Independent risk factors for death within 30 days after
      surgery were age >= 71 years, male gender, ASA grade >= III, palliative outcome,
      free or iatrogenic tumour perforation, splenectomy, intraoperative surgical
      adverse events and postoperative medical complications (VIII). SEMS placement
      performed on the indication acute bowel obstruction in patients with potentially
      curable disease can be accomplished with high technical and clinical success
      rates. The perforation rate, however, may reach 12%. Even so, the mortality rate
      within 30 days after a SEMS attempt and later surgery may, irrespective of its
      timing, by very low (3%) relative to the mortality seen after emergency surgery
      (IX). Long-term survival. The 5-year relative survival improved by 9% for both
      colonic and rectal cancer from 1977-1982 to 1995-1999 (I). Further improvement
      has been observed and in 2004-2006, the 5-year relative survival from colonic
      cancer was 52% (95% CI 51-54) for men and 57% (95% CI 55-58) for women. For
      rectal cancer the corresponding percentages were 55% (95% CI 53-57) and 57% (95%
      CI 55-59) (202). Overall, from 1977 until 2006, 1-year and 5-year survival
      increased almost 0.5-1% annually. Long-term survival has improved more in rectal
      cancer than in colonic cancer and survival from rectal cancer surpassed that of
      colonic cancer in the 2000s (202,204). Elderly patients aged >75 years
      experienced a marked 13-16% increase in relative survival from 1977-1982 to 1995
      1999, i.e., a period during which the rate of curative surgery increased
      pronouncedly among the elderly (III). The survival improvement among their
      younger counterparts in that period only reached 7%. Mortality from colorectal
      cancer was only excessive in the elderly during the first two years after
      surgery. In 1995-2006, about 30-43% of colorectal cancer patients had moderate
      and severe comorbidity as determined by a Charlson Comorbidity score of 1-2 and
      3+, respectively. These comorbid patients had a long-term survival inferior to
      that of patients with no comorbidity. In colonic cancer, the 5-year survival in
      1998-2000 was 43% in patients with no comorbidity and only 20% in patients with
      severe comorbidity. Comorbidity had an even stronger impact in rectal cancer
      (VI). Evidence repeatedly demonstrates a volume-outcome effect on long-term
      survival from colonic and rectal cancer with improved survival being
      significantly associated with increasing hospital caseload and surgeon's
      education/specialty (V). In addition, the most recent evidence reveals that
      surgeon caseload may have a stronger impact on long-term survival than hospital
      volume which reflects the complexity in the interaction between hospital caseload
      and surgeon caseload. A total therapeutic delay >= 60 day has been shown to have
      a negative impact on the long-term survival from rectal cancer, but not from
      colon cancer, given that stage is an intermediate step in the causal pathway
      between delay and survival (X). Neither provider delay >= 60 days, nor hospital
      delays >= 30 days or >= 60 days had any prognostic impact on long-term survival
      from colorectal cancer. Emergency surgery for colonic cancer is associated with
      an inferior long-term survival. The 5-year survival after acute curative surgery
      in Denmark is 39% (16). However, the use of SEMS as bridge to elective curative
      surgery makes it possible to achieve 3-year survival rates similar to those of
      75% seen after elective curative surgery for colonic cancer (IX) - despite an
      unexpectedly high perforation rate.

PMID- 22459727
TI  - Detection of risk factors for difficult tracheal intubation.
AB  - Several studies have identified difficult airway management including a difficult
      tracheal intubation of patients undergoing general anaesthesia as a major cause
      of anaesthesia-related morbidity and mortality. Therefore it is presumed that a
      difficult tracheal intubation is a surrogate marker for morbidity and mortality,
      and by reducing the prevalence of difficult tracheal intubation then morbidity
      and mortality will be reduced as well. From the Danish Anaesthesia Database
      (DAD), we retrieved a cohort of consecutive patients planned and attempted for
      tracheal intubation by direct laryngoscopy. Based upon various data including an
      intubation score registered in the database, we aimed to evaluate four different
      parameters, 'Obesity', 'avoidance of neuromuscular blocking agents', 'a previous
      difficult tracheal intubation' and 'the modified Mallampati-score', as possible
      risk factors for a difficult tracheal intubation.  All of these risk factors were
      statistically associated with a difficult tracheal intubation, but the clinical
      significance varied substantially. However, neither 'obesity', 'the modified
      Mallampati-score' nor 'a previous difficult tracheal intubation' were sufficient
      as stand-alone tests for prediction of difficult tracheal intubation. In
      multivariate analyses the impact of obesity on the risk of difficult tracheal
      intubation seems weak, while both 'the modified Mallampati-score' and 'a previous
      difficult tracheal intubation' demonstrated to be clinically strong risk factors
      for difficult tracheal intubation. The evaluation of 'avoidance of neuromuscular
      blocking agents' as a risk factor differ substantially from the other
      assessments, as it concerns the impact of an intervention rather than of a
      patient-related risk factor for difficult tracheal intubation. In our assessment,
      'avoiding neuromuscular blocking agents' was demonstrated as a possible risk
      factor for difficult and abandoned tracheal intubation independent of other risk
      factors recorded in the DAD.  Several previous studies have failed to present
      specific risk factors that could identify difficult intubation or laryngoscopy by
      itself. Therefore it seems rational to focus on the development, testing and
      modification of multivariate models from large scale cohort studies, hereby
      making the prognostication operational in everyday clinical practice. From there
      the challenge may be to test the effectiveness of the use of such a model in
      order to evaluate whether it actually has the capability to reduce difficult
      tracheal intubation, complications, and mortality. It seems that such a trial
      should and could be conducted as a cluster randomized trial of anaesthesia
      departments within the framework of the DAD.

PMID- 22459728
TI  - Late morbidity after repair of aortic coarctation.
AB  - BACKGROUND: Repaired aortic coarctation(CoA) is associated with high long-term
      cardiovascular mortality and morbidity. Persisting hypertension and left
      ventricular dysfunction are possibly associated with residual or recurrent aortic
      arch obstruction (ReCoA) and abnormal activation of vasoactive hormones.
      Furthermore, knowledge regarding these patients' functional health status late
      after repair is missing. STUDY SUBJECTS: A total of 133 adults who underwent
      surgical repair of CoA in childhood and youth (84 men) were examined in this
      observational cohort study. Median age (range) at surgery was 10 (0.1-40) years
      and 44 (26-74) years at examination. Thirty-six age and gender-matched healthy
      subjects served as controls. OUTCOME MEASURES: Prevalence of previous
      cardiovascular reintervention, current cardiac and valvular function, exercise
      capacity, blood pressure levels, as well as the presence of residual or recurrent
      aortic arch obstruction (ReCoA) and aortic aneurysms. METHODS: Echocardiography
      (including tissue Doppler), bicycle exercise testing, 24-h ambulatory blood
      pressure monitoring, MRI/ CT scan of the thoracic aorta were performed. Analysis
      of renal function and vasoactive hormones was performed by blood and urine tests
      at rest and after maximal physical effort. Functional health status was assessed
      by means of the SF-36 health survey. RESULTS: The prevalence of hypertension was
      high (44% of the cohort had blood pressure levels above the recommended levels,
      half of those despite medication). Reinterventions were common (26%) and most
      often performed due to aortic valve dysfunction and ReCoA. Above half of the
      cohort had a bicuspid aortic valve, which was strongly associated with ascending
      aorta aneurysms and aortic valve regurgitation. A total of 48% of the patients
      had a mild to moderate ReCoA, which was only weakly associated with the presence
      of hypertension as well as to exercise capacity and echocardiographic
      measurements of cardiac function. Both normotensive and hypertensive patients had
      increased left ventricular mass, normal ejection fraction, reduced long-axis
      systolic function, and impaired diastolic function compared with controls, with
      differences being more pronounced in hypertensive patients. Natriuretic hormone
      levels were slightly increased among normotensives, whereas renin-angiotensin
      aldosterone and renal function parameters were normal at rest and during
      exercise. Mild to moderate ReCoA had no significant influence on the measured
      parameters. SF-36 scores among patients were only slightly lower compared with
      those from controls. However, patients with reduced exercise performance and
      those taking daily cardiovascular medication scored significantly lower in
      several mental and physical categories compared with patients with unmedicated
      patient and with those with preserved exercise capacity. CONCLUSIONS: Surgical
      correction of CoA only repairs the anatomical narrowing, but not the associated
      vasculo- and valvulopathy. Increased left ventricular mass, systolic and
      diastolic dysfunction, aortic valve dysfunction, aortopathy, and hypertension are
      common. Morbidity is only weakly associated with mild and moderate degrees of
      ReCoA, and not associated with changes in vasoactive hormone levels and renal
      function. Despite late morbidity, functional health status is overall only
      slightly impaired in patients after surgical correction of CoA compared with
      healthy subjects. Nevertheless, the subgroup with reduced exercise capacity and
      need for cardiovascular medications have a considerable impairment of both
      physical and mental aspects of functional health.

PMID- 22459729
TI  - Telephone-based guided self-help for adolescents with chronic fatigue syndrome: A
      non-randomised cohort study.
AB  - The aim of this study was to gain preliminary evidence about the efficacy of a
      new telephone-based guided self-help intervention, based on cognitive-behavioural
      principles, which aimed to reduce fatigue and improve school attendance in
      adolescents with chronic fatigue syndrome (CFS). A non-randomised cohort design
      was used, with a two-month baseline period. Sixty-three 11-18 year-old
      participants recruited from a specialist CFS unit received the intervention.
      Participants received six half-hour fortnightly telephone sessions and two follow
      up sessions. Fatigue and school attendance were the main outcomes and the main
      time point for assessing outcome was 6 months post-treatment. Using multi-level
      modelling, a significant decrease in fatigue was found between pre-treatment and
      6 month follow-up, treatment effect estimate = - 5.68 (-7.63, -3.72), a large
      effect size (Cohen's d = 0.79). The decrease in fatigue between pre and post
      treatment was significantly larger than between baseline and pre-treatment. A
      significant increase in school attendance was found between pre-treatment and 6
      month follow-up, effect estimate = 1.38 (0.76, 2.00), a medium effect size (d = 
      0.48). univariate logistic regression found baseline perfectionism to be
      associated with better [corrected] school attendance at six-month follow-up. In
      conclusion, telephone-based guided self-help is an acceptable minimal
      intervention which is efficacious in reducing fatigue in adolescents with CFS.

PMID- 22459730
TI  - Cross-US reinstatement of human conditioned fear: return of old fears or
      emergence of new ones?
AB  - Re-exposure to the unconditioned stimulus (US) following fear extinction in the
      laboratory produces reinstatement of fear. Similarly in clinical situations,
      anxiety patients may experience adverse events that reinstate fear following
      successful exposure therapy. The current study employed two USs, shock and loud
      noise, to examine whether a US that is qualitatively different but of the same
      valence as the original acquisition US can produce reinstatement in human fear
      conditioning. Both standard and cross-US reinstatement manipulations led to
      elevated fear as indexed by skin conductance. However, cross-US reinstatement was
      accompanied by elevated expectancy of the US that had been presented during the
      reinstatement manipulation, not the US that had been used to establish fear in
      acquisition. This result implies that reinstatement may involve the development
      of new fears. Context conditioning and cognitive processes were implicated as
      possible mechanisms. The current findings suggest that clinical relapse
      attributed to reinstatement may not always reflect the reactivation of old fears
      but may instead represent new fears worthy of clinical examination.

PMID- 22459731
TI  - Development and preliminary evaluation of a psychosocial intervention for
      modifying psychosocial risk factors associated with foot re-ulceration in
      diabetes.
AB  - Diabetic foot ulcers are a common, chronic and costly complication of Diabetes,
      with the greatest risk for ulceration being previous ulceration. Previous
      approaches to reducing re-ulceration risk have not, however, considered the
      psychosocial factors which may influence this risk. We reviewed the existing
      evidence in this area and developed a therapeutic model which informed the
      content, structure and format of a psychosocial intervention designed to modify
      the psychosocial risk factors associated with re-ulceration. The intervention was
      subjected to a qualitative evaluation in a feasibility study which involved a
      randomised controlled trial in which 10 individuals were randomised to receive
      the intervention and 5 individuals to usual care. Individuals in both arms
      participated in in-depth qualitative interviews after the first 10 weeks of the
      intervention and again after the final maintenance session. The intervention was
      perceived as acceptable and patients' reported evidence of sustained change in
      several of the psychosocial risks identified in the therapeutic model. These
      observations were supported in the descriptive findings obtained from
      questionnaires measuring mood, cognitions, behaviour and social support. The
      intervention appears to offer an acceptable and effective way of modifying the
      psychosocial risk factors associated with re-ulceration.

PMID- 22459732
TI  - Effects of emotion regulation strategies on smoking craving, attentional bias,
      and task persistence.
AB  - The goal of this study was to investigate the effects of different strategies for
      regulating emotions associated with smoking on subjective, cognitive, and
      behavioral correlates of smoking. Emotion regulation was manipulated by
      instructing participants to reappraise (n = 32), accept (n = 31), or suppress (n
      = 31) their emotions associated with smoking. The dependent measures included
      subjective reports of craving, negative affect, and attentional biases, as
      measured by a modified dot-probe task, and persistence during a task to measure
      distress tolerance. Individuals who were encouraged to reappraise the
      consequences of smoking showed diminished craving, lower negative affect, had
      reduced attentional biases for smoking-related cues, and exhibited greater task
      persistence than those who were instructed to accept and suppress their urge to
      smoke. These findings suggest that reappraisal techniques are more effective than
      acceptance or suppression strategies for targeting smoking-related problems.

PMID- 22459733
TI  - Applicability of a cognitive model of worry to children and adolescents.
AB  - BACKGROUND: Intolerance of uncertainly (IU), cognitive avoidance (CA) and
      positive beliefs about worry (PB) independently predict worry frequency in older
      adolescents and adults, and when targeted together in treatment produce
      significant reductions in both worry and anxiety in this age range. The present
      study addresses a gap in the literature by testing whether a cognitive model of
      excessive worry and anxiety incorporating these process variables is applicable
      to children and adolescents. METHOD: Primary and secondary school students (n =
      515; aged 7-19 years) completed modified self-report measures of worry frequency,
      anxiety, IU, CA and PB and a path analysis undertaken to test whether IU was a
      higher order variable for CA and PB and whether the relationship between IU/CA/PB
      and anxiety was mediated by worry frequency. RESULTS: Significant (bivariate)
      correlations were observed between the measures of IU, PB, CA, worry and anxiety
      across the age range. However separate path models had to be fitted for children
      (aged 7-12 years) and adolescents (aged 13-19) with PB being dropped from the
      child model. CA was related to anxiety only through worry in children while IU
      showed direct paths to worry and anxiety in both children and adolescents.
      CONCLUSIONS: Cognitive models of persistent worry in adults and older adolescents
      may, with some modification, have applicability to children. Further testing and
      refinement of these cognitive models of worry may lead to improvements in
      existing treatments for anxious youth.

PMID- 22459734
TI  - Dried blood spot analysis combined with limited sampling models can advance
      therapeutic drug monitoring of tuberculosis drugs.

PMID- 22459735
TI  - Probable corticosteroid-induced reactivation of latent hepatitis B virus
      infection in an HIV-positive patient involving immune escape.
AB  - We describe a patient infected with human immunodeficiency virus who possessed a
      serological profile suggesting a previous cleared acute hepatitis B virus (HBV)
      infection, including high levels of antibodies against HBV surface antigen (anti
      HBs). Following the administration of inhaled glucocorticosteroids combined with
      protease inhibitor-based antiretroviral treatment, the patient developed an
      unexpected severe acute hepatitis despite persistence of anti-HBs. A genotype A2
      strain emerged with 2 major mutations in the S gene, sK122R and sD144E. Molecular
      and biological analyses strongly suggested reactivation of a latent HBV
      infection. The importance and the molecular basis of these 2 epitopes in immune
      escape mechanisms and host-virus interactions are discussed.

PMID- 22459737
TI  - The differential clinical impact of human coronavirus species in children with
      cystic fibrosis.
AB  - We investigated the clinical impact of human coronaviruses (HCoV) OC43, 229E,
      HKU1 and NL63 in pediatric patients with cystic fibrosis (CF) during routine and
      exacerbation visits. A total of 408 nasopharyngeal aspirate samples were obtained
      from 103 patients over a 1-year period. Samples positive for HCoV were submitted
      for nucleotide sequencing to determine the species. Nineteen samples (4.65%) were
      positive for HCoV, of which 8 were positive for NL63, 6 for OC43, 4 for HKU1, and
      1 for 229E. Identification of HCoV was not associated with an increased rate of
      respiratory exacerbations, but NL63-positive patients had higher exacerbation
      rates than patients who were positive for other HCoV species.

PMID- 22459738
TI  - Genetic and immunological evidence implicates interleukin 6 as a susceptibility
      gene for leprosy type 2 reaction.
AB  - In leprosy, type 1 reaction (T1R) and type 2 reaction (T2R) are major causes of
      nerve injury and permanent disabilities. A previous study on plasma levels of 27
      cytokines in patients with T1R or T2R and controls with nonreactional leprosy
      identified the gene for interleukin 6 (IL-6) as a candidate for genetic analysis.
      Two nested case-control studies were built from a cohort of 409 patients with
      leprosy from central Brazil, monitored for T1R and T2R. There was evidence for
      association between T2R and IL-6 tag single-nucleotide polymorphisms rs2069832 (P
      = .002), rs2069840 (P = .03), and rs2069845 (P = .04), with information on the
      entire IL-6 locus, as well as functional IL-6 variant rs1800795 (P = .005).
      Moreover, IL-6 plasma levels in patients with T2R correlated with IL-6 genotypes
      (P = .04). No association was found between IL-6 variants and T1R. Identifying
      genetic predictive factors for leprosy reactions may have a major impact on
      preventive strategies.

PMID- 22459739
TI  - Estimating the variability in the risk of infection for hepatitis C in the
      Glasgow injecting drug user population.
AB  - Glasgow (Scotland's largest city) has a high prevalence of injecting drug use and
      has one of the highest prevalences of hepatitis C virus (HCV) infection in
      injecting drug users (IDUs) in Western Europe. HCV prevalence data from surveys
      of Glasgow's IDUs from 1990 to 2007 were utilized and a model was applied that
      described the prevalence of HCV as a function of the rate (force) of infection.
      Force-of-infection estimates for HCV that may vary over time and injecting career
      length over a range of variables were investigated. New initiates to injecting
      were found to be at increased risk of HCV infection, with being recruited from a
      street location and reporting injecting in prison leading to a significant
      increase in the risk of infection in new initiates. These results indicate areas
      of importance for the planning of public health measures that target the IDU
      population.

PMID- 22459740
TI  - [Reinvestment in health: fundamentals, clarifications, experiences and
      perspectives].
AB  - During the economic crisis, the pressure to reduce health services expenditure as
      an isolated measure is greater than measures intended to increase the efficiency
      of these services. Information, methods and experiences to improve health
      outcomes with limited resources are available and a number of countries have been
      applying measures to achieve this goal. One of these measures is disinvestment.
      Given that this tactic is necessary but also intricate, allergenic and confusing,
      this article tries to clarify its meaning, place it in its correct context, and
      describe the methods and criteria used to identify and prioritize candidate
      medical technologies for disinvestment. The experiences of Spain, New Zealand,
      Australia, Canada, the United Kingdom and Italy in this endeavor are reviewed, as
      well as the obstacles faced by these countries when disinvesting and their mid
      term perspectives. Ignorance does not excuse its application, regardless of
      whether there is a crisis or not. Efforts to improve social efficiency are a
      permanent obligation of the national health system.

PMID- 22459741
TI  - [Characterization of folate supplementation in pregnancy, based on a combination
      of health information systems].
AB  - OBJECTIVES: To explore the utility of combining health information systems from
      the Valencia Health Agency to characterize folate supplementation in pregnant
      women in the autonomous region of Valencia (Spain). METHODS: The cohort comprised
      women who gave birth during 2009 in hospitals within the Valencian Health Agency.
      These women were retrospectively followed-up using ABUCASIS electronic medical
      records and the GAIA electronic prescription system to identify folate
      consumption in the 3 months before and after conception. RESULTS: In 2009, there
      were 38,069 births in hospitals of the Valencian Health Agency, of which 37,040
      (97.3%) were included for analysis. In 34% of women, at least one folate
      dispensation was registered with an official prescription form within the
      periconceptional period (6.6% in the 3 months prior to conception). Dispensation
      with an official prescription form was associated with older women, free
      pharmaceutical prescriptions, birth in Spain, antiepileptic medications, and a
      diagnosis of diabetes. Eight percent of women (23.6% of the folate-treated women)
      received folates at high doses. CONCLUSIONS: Folate consumption during pregnancy
      is systematically under-registered by healthcare information systems because
      health professionals do not use the official prescription form for prescription
      and dispensation. Database linkage is an inadequate approach to assess folic acid
      supplementation during pregnancy.

PMID- 22459742
TI  - Statin therapy is associated with aneurysm sac regression after endovascular
      aortic repair.
AB  - BACKGROUND: Several anatomic factors have been identified as predictive of sac
      behavior after endovascular aneurysm repair (EVAR). The effects of statin therapy
      on aneurysm sac size reduction remain controversial. This study tested the
      hypothesis that statin therapy enhances aneurysmal sac regression after EVAR.
      METHODS: This monocentric retrospective study included patients with abdominal
      aortic aneurysms treated by EVAR using the Zenith (Cook, Bloomington, Ind) graft
      device. We excluded patients presenting with perioperative sac enlargement
      factors such as endoleaks, endotension, infectious, inflammatory, ruptured, or
      anastomotic aneurysms. We prospectively assessed standard clinical and anatomic
      data, as well as statin use, at the time of EVAR and during follow-up. The
      primary end point was the decrease in the largest transverse aortic diameter at
      24 months compared with the preoperative diameter. RESULTS: Among 166 patients
      treated by a Zenith device and meeting the inclusion criteria, 120 were
      identified as statin users and 46 as nonstatin users, with comparable
      characteristics. At 24 months of follow-up, statin group patients had a greater
      aneurysm sac reduction (25% vs 14%; P < .0001). At a threshold of 5 mm in
      diameter regression, statin use was a positive factor of retraction (odds ratio,
      7.93; 95% confidence interval, 3.22-15.52; P < .0001). Multivariate analysis
      revealed statin use was an independent predictive factor of sac regression
      (adjusted odds ratio, 9.39; 95% confidence interval, 3.45-25.56). CONCLUSIONS:
      This study showed that statin use was predictive of sac regression after EVAR
      with the Zenith graft device. This effect needs to be confirmed by larger
      randomized trials or by large population evaluation.

PMID- 22459743
TI  - Adjunctive use of the superficial femoral vein for vascular reconstructions.
AB  - OBJECTIVE: Although the superficial femoral vein (SFV) is an accepted treatment
      for aortic graft infections, this conduit also has potential uses in other areas.
      Herein, we evaluate our experience using the SFV for arterial and venous bypasses
      and the arteriovenous (AV) fistula for dialysis access. METHODS: Between 1999 and
      2011, 42 patients underwent a bypass or a thigh AV fistula using the SFV (31
      arterial, four central venous, six AV fistulas, and one common carotid-to
      vertebral bypass). Indications for arterial bypass included infected graft (20),
      critical limb ischemia (nine), and failed bypass (six). Indications for central
      venous bypass were: superior vena cava syndrome (two), vessel reconstruction due
      to tumor encasement (one), and central vein occlusion from thoracic outlet
      syndrome (one). All AV fistulas were created after patients sustained bilateral
      subclavian vein occlusions from failed upper extremity access. The common carotid
      to-vertebral bypass was created due to an occluded vertebral artery with
      resultant stroke. RESULTS: Kaplan-Meier cumulative patency curves were used. The
      primary patency rates at 30 days, 1 year, and 3 years were 97.4% (95% confidence
      interval [CI], 92.41-100), 74.6% (95% CI, 57.89-96.23), and 66.4% (95% CI, 47.06
      93.53), respectively. The assisted primary patency rates at 30 days, 1 year, and
      3 years were 100% (95% CI, 100-100), 97.1% (95% CI, 91.54-100), and 89% (95% CI,
      74.29-100), respectively. Secondary patency rates at 30 days, 1 year, and 3 years
      were 100% (95% CI, 100-100), 97.1% (95% CI, 91.54-100), and 89% (95% CI, 74.29
      100), respectively. Limb salvage rates at 30 days, 1 year, and 3 years were 97.3%
      (95% CI, 92.21-100), 93.6% (95% CI, 78.35-100), and 93.6% (95% CI, 78.35-100),
      respectively. Survival rates at 30 days, 1 year, and 3 years were 97.6% (95% CI,
      92.95-100), 86% (95% CI, 75.3-98.3), and 86% (95% CI, 75.3-98.3), respectively.
      Follow-up ranged from 1 month to 8.7 years (mean time, 21 months). Complications
      occurred in 22 patients (52%) and included wound complications (n = 19; 45.2%);
      deep vein thrombosis (n = 1; 2.4%); anastomotic breakdown (n = 1; 2.4%); hematoma
      (n = 4; 9.5%); pulmonary embolism (n = 2; 4.8%); and compartment syndrome (n = 2;
      4.8%). CONCLUSIONS: The SFV is a durable conduit for uses beyond aortic
      reconstruction and should be considered when the great saphenous vein is not
      available or size match is a concern. However, wound complications remain a
      problem.

PMID- 22459744
TI  - Carotid endarterectomy is more cost-effective than carotid artery stenting.
AB  - OBJECTIVE: Cost-effectiveness has become an important end point in comparing
      therapies that may be considered to have clinical equipoise. While controversial,
      some feel that recent multicenter randomized controlled trials have codified
      clinical equipoise between carotid endarterectomy (CEA) and carotid artery
      stenting (CAS). METHODS: A retrospective analysis of hospital cost and 30-day
      clinical outcomes was performed on patients undergoing CEA and CAS between
      January 1, 2008 and September 30, 2010 at a single tertiary referral institution.
      Cost, not charges, of the index hospitalization was divided into supply, labor,
      facility, and miscellaneous categories. All costs were normalized to 2010 values.
      RESULTS: A total of 306 patients underwent either CEA (n = 174) or CAS (n = 132).
      Mean hospital cost for CAS was $9426 +/- $5776 while CEA cost was $6734 +/- $3935
      (P < .0001). This cost differential was driven by the significantly higher direct
      supply costs for CAS ($5634) vs CEA ($1967) (P <= .0001). The higher costs for
      CAS were seen consistently in symptomatic, asymptomatic, elective, and urgent
      subgroups. Patients undergoing CAS who were enrolled in a trial or registry
      (53.8%) incurred significantly less cost ($7779 +/- $3525) compared to those who
      were not ($11,279 +/- $7114; P = .0004). Patients undergoing CEA trended toward a
      higher prevalence of being symptomatic (44.8%) compared to CAS (34.0%; P = .058).
      Age was not significantly different between patients undergoing CEA and CAS (70.2
      vs 72.0, respectively; P = .36). Coronary artery disease was more common in
      patients undergoing CAS (60.3% vs 39%; P = .0001). The prevalence of chronic
      obstructive pulmonary disease, renal failure, hypertension, and diabetes was not
      significantly different between cohorts. Thirty-day combined
      stroke/death/myocardial infarction rate was 2.3% (4 of 174) in the CEA group and
      3.8% (5 of 132) in the CAS group, P = .5. Overall length of stay (LOS) was 2.1
      days in both groups (P = .9). LOS was higher for urgent interventions (7.3-7.5
      days) and symptomatic status (2.9-3.5 days) when compared to patients treated
      electively (1.3-1.4 days). CONCLUSIONS: Treatment of carotid disease with CAS was
      40% more costly than CEA and did not provide better clinical outcomes or a
      reduction in LOS. These trends were consistent in symptomatic, asymptomatic,
      urgent, and elective subgroups At present, CAS cannot be considered a cost
      effective treatment for carotid disease.

PMID- 22459745
TI  - Impact of anterior scalene lidocaine blocks on predicting surgical success in
      older patients with neurogenic thoracic outlet syndrome.
AB  - OBJECTIVE: Surgical management of neurogenic thoracic outlet syndrome (NTOS) is
      controversial due to the lack of predictors of success and difficulties in
      patient selection. We sought to examine the effects of patient demographics,
      etiology, duration of symptoms, and the selective use of lidocaine and botulinum
      toxin anterior scalene blocks on outcomes of patients undergoing transaxillary
      decompression with first rib resection and scalenotomy for NTOS. METHODS:
      Patients with NTOS who had failed physical therapy and had transaxillary
      decompression between 2003 and 2009 were reviewed retrospectively from a
      prospectively maintained database. Patients were stratified to age groups < 40
      and >= 40 years old. Bivariate and multivariate statistical models of analysis
      were used. RESULTS: One hundred fifty-nine procedures (16 patients bilateral;
      three patients with cervical ribs; 84.3% women; median age, 37 years; range, 21
      64 years) were identified. Ninety-six patients were < 40 and 63 were >= 40 years
      old. Etiology was similar in both groups: trauma 43% vs 46% and chronic
      repetitive motion 57% vs 54%. Duration of symptoms was less in the <40 group
      (38.4 vs 66 months; P < .05). More patients in the >= 40 group had other spine,
      shoulder, or arm operations (38% vs 18%; P < .05). Median follow-up for the
      cohort was 12 months. Transaxillary decompression was more likely to relieve
      symptoms in patients <40 vs >= 40 years old (90% vs 78%; P < .05). Lidocaine
      blocks were positive in 89% (49 of 55 patients) in the <40 group and 93% (43 of
      46 patients) in the >= 40 group. After adjusting for patient presenting factors
      in multivariate analysis, the impact of a successful lidocaine block in patients
      >= 40 years old was greater than in patients < 40 years old (improvement of
      surgical success of 14% in the > 40 group vs 7% in the < 40 group; P = .05).
      Botulinum toxin blocks were successful in less patients, 38% (eight of 21
      patients) in the < 40 group and 52% (12 of 23 patients) in the >= 40 group but
      were not predictive of symptom relief after transaxillary decompression.
      CONCLUSIONS: Although patients with NTOS < 40 years old achieve more symptom
      relief overall after transaxillary decompression as compared to patients >= 40
      years old, the selective use of lidocaine blocks is more beneficial in predicting
      surgical success in patients >= 40 years old given that younger patients < 40
      years old seem to do well regardless.

PMID- 22459746
TI  - Thirty-day outcome and quality of life after endovascular abdominal aortic
      aneurysm repair in octogenarians based on the Endurant Stent Graft Natural
      Selection Global Postmarket Registry (ENGAGE).
AB  - OBJECTIVE: To determine 30-day outcome and quality of life after elective
      endovascular abdominal aortic aneurysm repair in octogenarians. METHODS: From
      March 2009 to May 2011, 1200 patients with abdominal aortic aneurysms were
      treated with endovascular aneurysm repair (EVAR) using the Endurant stent graft
      were included in the Endurant Stent Graft Natural Selection Global Postmarket
      Registry (ENGAGE) registry. Among these, 926 (77%) were aged <80 years, and 274
      (23%) were aged >= 80 years. Quality of life was assessed using composite EuroQoL
      5-Dimensions Questionnaire index scores. RESULTS: Gender was unequally
      distributed, with more female patients among the octogenarians (P = .043).
      Octogenarians had a significantly higher American Society of Anesthesiologists
      classification (P < .001) and differed significantly in baseline risk factors.
      The younger cohort was more likely to smoke (P < .001) and be alcoholics (P =
      .005). Octogenarians had larger aortic aneurysm (P = .010) and left iliac artery
      diameters (P = .017) and greater infrarenal neck angulation (P = .01). The
      technical success rate was >99% for both cohorts. Octogenarians were more often
      operated on under general anesthesia (P = .028), had a longer procedure duration
      (P = .001), and an increased length of hospitalization; both total (P < .001) and
      postprocedure (P < .001). All-cause mortality and major adverse event rates were
      similar in the two groups (P = .835 and P = .186, respectively). There was no
      difference in the number of secondary endovascular procedures or aneurysm rupture
      at 30 days. At discharge, both groups had reduced health status dimensions,
      except anxiety/depression, when compared with baseline. At 30 days, the
      octogenarian group had a lower composite EuroQoL 5-Dimensions Questionnaire index
      compared with the younger group, indicating a slower recovery (0.83 +/- 0.20 vs
      0.87 +/- 0.16; P = .003). CONCLUSIONS: Octogenarians can be safely treated using
      the Endurant stent graft with a high technical rate of success, low perioperative
      mortality, and no reduction in quality of life. Octogenarians did, however,
      appear to recover more slowly than younger patients with respect to certain
      quality of life components. Long-term data are needed to confirm these results.

PMID- 22459747
TI  - Changes in baroreceptor sensitivity after eversion carotid endarterectomy.
AB  - OBJECTIVE: Posteversion carotid endarterectomy hypertension has been suggested to
      be associated with impaired baroreceptor sensitivity (BRS), which has been
      identified as a factor of prognostic relevance in patients with cardiovascular
      disease. The aim of this prospective single-center nonrandomized study was to
      describe the changes of BRS in the early postoperative period after eversion
      carotid endarterectomy (E-CEA). METHODS: Spontaneous BRS and hemodynamic
      parameters such as blood pressure (BP), heart rate (HR), cardiac output (CO), and
      total peripheral resistance (TPR) were evaluated preoperatively as well as
      postoperatively after 1 and 3 days using a noninvasive sequential cross
      correlation method. Additionally, any modification in vasoactive medication due
      to BP derangement in the postoperative period was noted. Due to non-normal
      distribution of BRS, HR, and TPR samples, all measured values were expressed as
      medians with interquartile range (IQR), and a nonparametric test (Friedman) was
      performed. After adjustment for multiple testing, differences were considered
      statistically significant when the two-tailed P value was less than .0036.
      RESULTS: Thirty-five patients (mean age, 71 years) with symptomatic or
      asymptomatic internal carotid artery stenosis were included. The BRS
      significantly decreased to a lower level 24 hours after surgery (4.71 ms/mm Hg
      [3.02-6.1]) than preoperatively (5.95 ms/mm Hg [4.68-10.86]; P < .0001),
      resulting in a within-patient difference of -2.46 ms/mm Hg (95% confidence
      interval [CI], -8.38 - -1.52). This difference (95% CI, [- 1.58 (-8.24 - -0.80)])
      persisted at the 72-hour measurements (5.63 ms/mm Hg [3.23-7.69]; P = .0005). The
      HR, reflecting the sympathetic activity, increased 24 hours after the operation
      (69 bpm [61.3-77.7]) compared with preoperative values (63 bpm [57.9-73.2]; P =
      .005) (within-patient difference [95% CI] 3.7 [1.5-8.5]), and this increase
      reached significance at 72 hours (69 bpm [65.4-77.5]; P = .001) (within-patient
      difference [95% CI] 5.5 [2.3-8.8]). Values of systolic pressure, diastolic
      pressure, mean arterial pressure, CO, and TPR were not significantly different
      between pre- and postoperative measurements. Overall, 23 (66%) patients developed
      significant postoperative hypertension requiring aggressive management with
      additional medications. CONCLUSIONS: E-CEA might have a decreasing influence on
      BRS, leading to increased sympathetic activity. Investigations of the longer-term
      effects of impaired BRS are warranted. These findings should be interpreted with
      caution, noting the limitation of an absent control group.

PMID- 22459748
TI  - Optimal exercise program length for patients with claudication.
AB  - BACKGROUND: This prospective, randomized controlled clinical trial determined
      whether an optimal exercise program length exists to efficaciously change
      claudication onset time (COT) and peak walking time (PWT) in patients with
      peripheral artery disease and claudication. METHODS: The study randomized 142
      patients to supervised exercise (n = 106) or a usual care control group (n = 36),
      with 80 completing the exercise program and 27 completing the control
      intervention. The exercise program consisted of intermittent walking to nearly
      maximal claudication pain 3 days per week. COT and PWT were the primary outcomes
      obtained from a treadmill exercise test at baseline and bimonthly during the
      study. RESULTS: After exercise, changes in COT (P < .001) and PWT (P < .001) were
      consistently greater than changes after the control intervention. In the exercise
      program, COT and PWT increased from baseline to month 2 (P < .05) and from months
      2 to 4 (P < .05) but did not significantly change from months 4 to 6 (P > .05).
      When changes were expressed per mile walked during the first 2 months, middle 2
      months, and final 2 months of exercise, COT and PWT only increased during the
      first 2 months (P < .05). CONCLUSIONS: Exercise-mediated gains in COT and PWT
      occur rapidly within the first 2 months of exercise rehabilitation and are
      maintained with further training. The clinical significance is that a relatively
      short 2-month exercise program may be preferred to a longer program to treat
      claudication because adherence is higher, costs associated with personnel and use
      of facilities are lower per patient, and more patients can be trained for a given
      amount of personnel time and resource utilization.

PMID- 22459749
TI  - Aortic remodeling after endovascular repair with stainless steel-based stent
      graft in acute and chronic type B aortic dissection.
AB  - OBJECTIVE: This study analyzes the experience of a single center using hybrid
      stainless steel-based endovascular stent graft repair of acute complicated and
      chronic type B aortic dissection aneurysm, and assesses the proximal and distal
      aortic morphologic changes of the midterm results. METHODS: Between November 2006
      and March 2011, 61 patients with type B aortic dissection underwent stainless
      steel-based stent graft repair and were divided into an acute complicated
      dissection group (AD; n = 33) and a chronic dissection aneurysm group (CD; n =
      28). Serial computed tomography (CT) images were obtained to evaluate the changes
      of true and false lumen diameter at four levels during the postoperative period.
      RESULTS: The stent graft was successfully implanted in all patients (100%), with
      two surgical mortalities in the AD group and low perioperative morbidity (3.6%)
      of stroke and paraplegia. The cumulative survival rates of the two groups were
      similar (77.6% and 89.0%; P = .585) in a mean follow-up period of 24.1 +/- 15.6
      months. Complete thrombosis of the thoracic false lumen down to the diaphragm
      level was achieved in 80.6% of the patients in the AD group and 88.5% in the CD
      group without significant difference (P = .221), but the complete regression rate
      of the thoracic false lumen down to the diaphragm level showed a tendency of
      propitious remodeling in the AD group (54.8% vs 30.8%; P = .068). During follow
      up, despite the proximal changes of stented true and adjacent false lumen
      diameter being significantly increased and decreased, respectively, in both acute
      and chronic settings (P < .05), they were less prominent at the distal aorta in
      the CD aneurysm group. Intimomedial erosion of the distal end of the stent graft
      occurred in both acute (n = 6; 18.9%) and chronic (n = 10; 35.7%; P = .121)
      dissection settings after mean follow-up of 14.0 +/- 4.8 months in the AD group
      and 24.8 +/- 5.9 months in the CD group. Three patients with chronic dissection
      developed either pseudoaneurysm or true lumen compromise by expanded false lumen
      thrombi and required re-endografting. CONCLUSIONS: Endovascular stainless steel
      based stent graft implantation with vascular bypass to gain a sufficient proximal
      landing zone is feasible for type B aortic dissection and has low early and
      midterm mortality and morbidity in both the acute and chronic phases. Although
      early intervention might result in more favorable aortic remodeling with a higher
      possibility of complete regression and lower risk of late distal erosion, longer
      term follow-up still necessitates continuous careful surveillance of the entire
      aorta, especially the distal condition.

PMID- 22459751
TI  - Results of external iliac artery reconstruction in avid cyclists.
AB  - OBJECTIVE: We report the midterm results of external iliac artery reconstruction
      in 25 high-performance cyclists. METHODS: Cyclists undergoing arterial
      reconstruction for symptomatic external iliac arteriopathy at a single
      institution between October 2004 and August 2010 were identified. With
      Institutional Review Board approval, data were collected from medical record
      review and telephone interview. Results were analyzed with chi(2) or independent
      t-test. RESULTS: Twenty-five patients (31 limbs) underwent operation, which
      included arterial reconstruction with or without inguinal ligament release. The
      average patient age at operation was 43.8 +/- 5.0 for graft and 35.1 +/- 1.9 for
      patch (P = .08). The average time from competitive cycling until operation was
      18.2 +/- 5.8 years for graft and 20.0 +/- 2.5 for patch repairs (NS). Patients
      included 14 males and 11 females. There were 23 unilateral and four bilateral
      arterial reconstructions, including 26 patch angioplasties for localized disease
      and five interposition grafts for extensive disease; three patients underwent
      contralateral reconstruction as a separate procedure. Concomitant ipsilateral
      inguinal ligament release was performed in 25 patients (28 limbs), with
      contralateral release done in 12 patients (12 limbs). Three patients with
      isolated ligament release required subsequent arterial intervention. Follow-up
      averaged 32 months (range, 2-74). Primary patency for all reconstructions was
      100%; the four reoperations (five limbs; one bilateral) were for symptom
      recurrence, two postgraft and two postangioplasty. Three reoperations were for
      recurrent intimal hyperplasia, one for disease distal to the anastomosis, and one
      for concomitant atherosclerotic disease. Based on available data, postexercise
      ankle-brachial indices were improved in 18 of 23 limbs. Seventeen patients
      completed questions regarding satisfaction: 10 were satisfied or very satisfied
      (zero graft, 10 patch; P = .25), while four were unsatisfied (three graft, two
      patch; P = .017, including one patient with both a patch and graft repair). All
      20 patients for whom follow-up data were available are still cycling, 10
      competitively. Two of the four reoperated patients were unsatisfied; all four are
      still cycling, one competitively. CONCLUSIONS: External iliac arteriopathy is a
      disease of prolonged, sustained, and repetitive trauma. Patch angioplasty yields
      a low rate of reoperation, more satisfied patients, return to competitive
      activity, and improvement in postexercise ankle-brachial indices. Interposition
      grafting is associated with slightly older patients, more extensive disease, and
      less satisfying results. Intimal hyperplasia is the most frequent complication
      necessitating reoperation. Both the decision to pursue arterial reconstruction
      and patient expectations must be tempered by the pattern of disease and the
      potential for unsatisfactory results.

PMID- 22459752
TI  - Bovine pericardial patch repair in infected fields.
AB  - OBJECTIVE: Bovine pericardial patches (BPP) are frequently used for arterial
      reconstruction, but little data exist regarding their ability to resist
      infection. We hypothesize that BPP would provide a reasonable alternative to
      autologous vein patches in infected fields. METHODS: We used BPP to repair 51
      arteriotomies (25 brachial, 23 femoral, three popliteal) in 48 consecutive
      patients (mean age, 68 years; 65% men, 75% diabetic, 67% dialysis dependent)
      undergoing removal of infected (33 gram-positive, three gram-negative, eight
      mixed flora, and four culture-negative) polytetrafluoroethylene grafts (35
      arteriovenous grafts, nine femoral-distal bypasses, and four femoral patch
      angioplasties) between January 2007 and January 2011. Patient records were
      retrospectively reviewed and outcomes, including death, rupture, secondary
      reconstruction, and infection, were recorded. RESULTS: Over a mean follow-up of
      2.1 years (range, 3-48 months), 50 of 51 patches remained in place without
      evidence of recurrent infection, rupture, or revision. One patient had acute
      rupture of a popliteal arteriotomy 1 week postrepair and had subsequent ligation
      and above-knee amputation. Eight of the 48 patients died from unrelated causes
      during follow-up (three withdrew from dialysis, three myocardial infarction, and
      two unknown). CONCLUSIONS: BPP provide a durable alternative to saphenous vein
      for arterial reconstruction following removal of infected arterial grafts.

PMID- 22459754
TI  - Preoperative predictive factors of aneurysmal regression using the reporting
      standards for endovascular aortic aneurysm repair.
AB  - BACKGROUND: Aneurysmal regression is a reliable marker for long-lasting success
      after endovascular aneurysm repair (EVAR). The aim of this study was to identify
      the preoperative factors that can predictably lead to aneurysmal sac regression
      after EVAR, according to the reporting standards of the Society for Vascular
      Surgery and the International Society of Cardiovascular Surgery (SVS/ISCVS).
      METHODS: From 199 patients treated by EVAR between 2000 and 2009, 164 completed
      computed tomography angiographies and duplex scan follow-up images were
      available. All computed tomography angiographies for enrolled patients in this
      retrospective study were analyzed with Endosize software (Therenva, Rennes,
      France) to provide spatially correct 3-dimensional data in accordance with
      SVS/ISCVS recommendations. Anatomic parameters were graded according to the
      relevant severity grades. A severity score was calculated at the aortic neck, the
      abdominal aortic aneurysm, and the iliac arteries. Clinical and demographic
      factors were studied. Patients with aneurysmal regression >5 mm were assigned to
      group A (mean age, 71.4 +/- 8.9 years) and the others to group B (76.3 +/- 8.3
      years). RESULTS: Aneurysmal regression occurred in 66 patients (40.2%; group A).
      Univariate analyses showed smaller severity scores at the aortic neck (P = .02)
      and the iliac arteries (P = .002) in group A and calcifications and thrombus were
      less significant at the aortic neck (P = .003 and P = .02) and at the iliac
      arteries (P = .001 and P = .02), and inferior mesenteric artery patency was less
      frequent (68.2% vs 82.7%, P = .04). Two multivariate analyses were done: one
      considered the scores and the other the variables included in the scores. In the
      first, the patients of group A were younger (P = .002) and aortic neck
      calcifications were less significant (P = .007). In the second, group A patients
      were younger (P < .001) and the aortic neck scores were smaller (P = .04). There
      was no difference between the two groups in the type of implanted endoprosthesis
      or in the follow-up (group A: 46.4 +/- 24 months; group B: 47.2 +/- 22 months; P
      = .35). CONCLUSIONS: In this study, the young age of the patients and their
      aortic neck quality, in particular the absence of neck calcification, appear to
      have been the main factors affecting aneurysm shrinkage, such that they represent
      a target population for the improvement of EVAR results.

PMID- 22459755
TI  - Society for Vascular Surgery (SVS) Vascular Registry evaluation of comparative
      effectiveness of carotid revascularization procedures stratified by Medicare age.
AB  - OBJECTIVE: Recent randomized controlled trials have shown that age significantly
      affects the outcome of carotid revascularization procedures. This study used data
      from the Society for Vascular Surgery Vascular Registry (VR) to report the
      influence of age on the comparative effectiveness of carotid endarterectomy (CEA)
      and carotid artery stenting (CAS). METHODS: VR collects provider-reported data on
      patients using a Web-based database. Patients were stratified by age and
      symptoms. The primary end point was the composite outcome of death, stroke, or
      myocardial infarction (MI) at 30 days. RESULTS: As of December 7, 2010, there
      were 1347 CEA and 861 CAS patients aged < 65 years and 4169 CEA and 2536 CAS
      patients aged >= 65 years. CAS patients in both age groups were more likely to
      have a disease etiology of radiation or restenosis, be symptomatic, and have more
      cardiac comorbidities. In patients aged <65 years, the primary end point (5.23%
      CAS vs 3.56% CEA; P = .065) did not reach statistical significance. Subgroup
      analyses showed that CAS had a higher combined death/stroke/MI rate (4.44% vs
      2.10%; P < .031) in asymptomatic patients but there was no difference in the
      symptomatic (6.00% vs 5.47%; P = .79) group. In patients aged >= 65 years, CEA
      had lower rates of death (0.91% vs 1.97%; P < .01), stroke (2.52% vs 4.89%; P <
      .01), and composite death/stroke/MI (4.27% vs 7.14%; P < .01). CEA in patients
      aged >= 65 years was associated with lower rates of the primary end point in
      symptomatic (5.27% vs 9.52%; P < .01) and asymptomatic (3.31% vs 5.27%; P < .01)
      subgroups. After risk adjustment, CAS patients aged >= 65 years were more likely
      to reach the primary end point. CONCLUSIONS: Compared with CEA, CAS resulted in
      inferior 30-day outcomes in symptomatic and asymptomatic patients aged >= 65
      years. These findings do not support the widespread use of CAS in patients aged
      >= 65 years.

PMID- 22459756
TI  - Analysis of Trichophyton antigen-induced contact hypersensitivity in mouse.
AB  - BACKGROUND: Trichophyton-induced superficial skin mycosis is a common infectious
      human disease, but the immunological mechanism against Trichophyton infection is
      unclear with regard to many points. Since Trichophyton cannot colonize mice,
      guinea pigs were used in previous experiments on Trichophyton infection. However,
      it is difficult to perform immunological and genetic analyses in guinea pigs.
      OBJECTIVE: The objective of this study was to establish a mouse Trichophytin
      associated inflammation model of superficial skin mycosis in which immunological
      and genetic analyses can be performed. METHODS: We established a mouse
      Trichophyton-induced contact hypersensitivity model by applying Trichophytin, the
      Trichophyton antigen, extracted from Trichophyton mentagrophytes, to mice. Using
      a Th1-dominant strain, C57BL/6, and a Th2-dominant strain, BALB/c, we
      investigated the expression of inflammatory cytokines and receptors of the innate
      immune system for fungi, TLR4, TLR2, and dectin-1, and their influences on
      responses of the acquired immune system. RESULTS: In C57BL/6 mice, expressions of
      IFN-gamma and IL-17 A in regional lymph nodes and IL-1beta, IFN-gamma, IL-6, and
      IL-23 in the inflammatory auricular skin were enhanced by Trichophytin challenge,
      suggesting that not only Th1 cells but also Th17 cells were induced. In BALB/c
      mice, expressions of IL-4 in regional lymph nodes, and TSLP and IL-4 in the
      auricular skin were enhanced by Trichophytin challenge. Interestingly, dectin-1
      neutralizing antibody inhibited the promotion of IFN-gamma production in C57BL/6
      mice, and dectin-1-expressing immune cells had crucial actions in Trichophyton
      induced IFN-gamma production. CONCLUSION: These results suggest that inflammatory
      mediators differently regulate Trichophytin-induced contact hypersensitivity on
      the basis of the status of host immunity.

PMID- 22459757
TI  - Transcriptional regulation of aluminium tolerance genes.
AB  - Trivalent aluminium (Al(3+)) is the major toxin encountered by plants on acid
      soils. These cations inhibit root growth by damaging cells at the root apex. The
      physiology and genetics of Al(3+) tolerance mechanisms involving organic anion
      efflux from roots have now been investigated in a range of species. Over the past
      decade, genes encoding these and other newly discovered mechanisms of tolerance
      have been cloned. In this review, we describe the genes controlling the genotypic
      variation in Al(3+) tolerance for several important crop species. We focus on
      recent insights into the transcriptional regulation of these and other genes
      involved in Al(3+) tolerance and discuss the pathways coordinating their
      expression in Arabidopsis and rice.

PMID- 22459758
TI  - Transcriptional machineries in jasmonate-elicited plant secondary metabolism.
AB  - Jasmonates (JAs) act as conserved elicitors of plant secondary metabolism. JA
      perception triggers extensive transcriptional reprogramming leading to the
      concerted activation of entire metabolic pathways. This observation inspired
      numerous quests for 'master' regulators capable of enhancing the production of
      specific sets of valuable plant metabolites. Many transcription factors (TFs),
      often JA-activated themselves, with a role in the JA-modulated regulation of
      metabolism were discovered. At the same time, it became clear that metabolic
      reprogramming is subject to complex control mechanisms integrated in robust
      cellular networks. In this review, we discuss current knowledge of the effect of
      JA-modulated TFs in the elicitation of secondary metabolism in the model plant
      Arabidopsis (Arabidopsis thaliana) and a range of medicinal plant species with
      structurally divergent secondary metabolites. We draw parallels with the
      regulation of secondary metabolism in fungi and consider the remaining challenges
      to map and exploit the transcriptional machineries that drive JA-mediated
      elicitation of plant secondary metabolism.

PMID- 22459759
TI  - Predicting resistance to health education messages for cannabis use: the role of
      rebelliousness, autic mastery, health value and ethnicity.
AB  - The prevalent use of cannabis by adolescents and young adults, combined with the
      common misconception that smoking cannabis is relatively harmless, warrants the
      exploration of factors influencing resistance to health education messages about
      cannabis use. This investigation did so within a Reversal Theory framework. One
      hundred and thirteen undergraduate students responded to an informative leaflet
      detailing the health effects of smoking cannabis. The most significant
      independent predictor of message resistance was frequency of cannabis use,
      followed by proactive rebelliousness, autic mastery, health value and ethnicity.
      These findings have implications for the development, design and targeting of
      cannabis health education programmes.

PMID- 22459761
TI  - Plant extracts for the control of bacterial growth: efficacy, stability and
      safety issues for food application.
AB  - The microbial safety of foods continues to be a major concern to consumers,
      regulatory agencies and food industries throughout the world. Many food
      preservation strategies have been used traditionally for the control of microbial
      spoilage in foods but the contamination of food and spoilage by microorganisms is
      a problem yet to be controlled adequately. Although synthetic antimicrobials are
      approved in many countries, the recent trend has been for use of natural
      preservatives, which necessitates the exploration of alternative sources of safe,
      effective and acceptable natural preservatives. Plants contain innumerable
      constituents and are valuable sources of new and biologically active molecules
      possessing antimicrobial properties. Plants extracts either as standardized
      extracts or as a source of pure compounds provide unlimited opportunities for
      control of microbial growth owing to their chemical diversity. Many plant
      extracts possess antimicrobial activity against a range of bacteria, yeast and
      molds, but the variations in quality and quantity of their bioactive constituents
      is the major detriments in their food use. Further, phytochemicals added to foods
      may be lost by various processing techniques. Several plant extracts or purified
      compounds intended for food use have been consumed by humans for thousands of
      years, but typical toxicological information is not available for them. Although
      international guidelines exist for the safety evaluation of food additives, owing
      to problems in standardization of plant extracts, typical toxicological values
      have not been assigned to them. Development of cost effective isolation
      procedures that yield standardized extracts as well as safety and toxicology
      evaluation of these antimicrobials requires a deeper investigation.

PMID- 22459760
TI  - Antimicrobial impact of the components of essential oil of Litsea cubeba from
      Taiwan and antimicrobial activity of the oil in food systems.
AB  - Using natural additives to preserve foods has become popular due to consumer
      demands for nature and safety. Antimicrobial activity is one of the most
      important properties in many plant essential oils (EOs). The antimicrobial
      activity of the essential oil of Litsea cubeba (LC-EO) from Taiwan and the
      antimicrobial impact of individual volatile components in the oil on pathogens or
      spoilage microorganisms: Vibrio parahaemolyticus, Listeria monocytogenes,
      Lactobacillus plantarum, and Hansenula anomala in vitro, and the antimicrobial
      activity of the LC-EO against these organisms in food systems were studied. The
      "antimicrobial impact" (AI) is a new term that combines the effects of minimal
      microbicidal concentration (MMC) and quantity of an antimicrobial substance. The
      AI can quantitatively reflect the relative importance of individual components of
      the EO on the entire antimicrobial activity of the EO. The MMCs of the LC-EO
      against V. parahaemolyticus, L. monocytogenes, L. plantarum, and H. anomala were
      determined as 750, 750, 1500, and 375 MUg/g, respectively in vitro. The MMCs of
      the LC-EO were 3000, 6000, and 12,000 MUg/g for L. monocytogenes in tofu stored
      at 4  degrees C, 25  degrees C, and 37  degrees C, respectively. The temperature
      affected the bacterial growth which consequently influenced the MMCs of the LC
      EO. The MMCs of the LC-EO were 3000, 6000, and 375 MUg/g for Vibrio spp. in
      oysters, L. plantarum in orange-milk beverage, and H. anomala in soy sauce,
      respectively. Except for soy sauce, the food systems exhibited marked matrix
      effects on diminishing the antimicrobial activity of the LC-EO. Averagely, citral
      accounted for ca 70% of the total AI value for all the tested organisms, and the
      rest of the AI value of the LC-EO was determined by all the tested compounds (ca
      4%) and the unidentified compounds (ca 26%).

PMID- 22459762
TI  - Enhancing the anticancer effect of the histone deacetylase inhibitor by
      activating transglutaminase.
AB  - Histone deacetylase (HDAC) inhibitors have shown promising anticancer effects in
      clinical trials. However, a proportion of patients do not respond to HDAC
      inhibitor therapy. We have previously demonstrated that tissue transglutaminase
      (TG2) is one of the genes commonly up-regulated by HDAC inhibitors in vitro and
      in vivo, and that two structurally distinct TG2 protein isoforms, the full-length
      (TG2-L) and the short form (TG2-S), exert opposing effects on cell
      differentiation due to difference in transamidation activity. Here we show that
      the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) transcriptionally
      activates the expression of both TG2-L and TG2-S, and that up-regulation of TG2-L
      renders neuroblastoma cells less sensitive to SAHA-induced cytotoxicity.
      Combination therapy with SAHA and the transamidation activator Naringenin, a
      natural product found in citrus fruits, synergistically enhanced transamidation
      activity and SAHA-induced cytotoxicity in neuroblastoma cells, but not in normal
      non-malignant cells. In tumour-bearing N-Myc transgenic mice, SAHA and Naringenin
      synergistically suppressed tumour progression. Taken together, our data
      demonstrate that SAHA-induced TG2-L over-expression renders cancer cells less
      sensitive to SAHA therapy, and suggest the addition of Naringenin to SAHA and
      probably also other HDAC inhibitors in future clinical trials in cancer patients.

PMID- 22459763
TI  - Ovarian function suppression and fulvestrant as endocrine therapy in
      premenopausal women with metastatic breast cancer.
AB  - BACKGROUND: Endocrine therapy is the preferred treatment for hormone-receptor
      (HR) positive metastatic breast cancer. In premenopausal patients, ovarian
      function suppression with goserelin in combination with anastrozole yielded
      promising results in phase II studies. Fulvestrant, a pure antioestrogen, yields
      high rates of disease stabilisation in postmenopausal women. Therefore, we
      investigated the feasibility and safety of fulvestrant plus goserelin in
      premenopausal women with HR-positive metastatic breast cancer. METHODS:
      Premenopausal patients with metastatic breast cancer eligible for endocrine
      treatment received fulvestrant 250 mg and goserelin 3.6 mg every four weeks as
      first- to fourth-line therapy. Clinical benefit rate (CBR; response rate plus
      disease stabilisation >= 6 months) was defined as the primary study end-point.
      Time to progression (TTP) and overall survival (OS) were estimated using the
      Kaplan-Meier product limit method. FINDINGS: Twenty-six patients received
      treatment as scheduled. 81% were pre-treated with tamoxifen and 69% had received
      prior aromatase inhibitors in combination with goserelin. The majority of
      patients (69%) presented with visceral metastases. Complete response was observed
      in a single patient, partial response in three and disease stabilisation >= 6
      months in eleven patients, resulting in a CBR of 58%. Median TTP was 6 months
      (95%confidence interval (CI), 2.4-9.6) and OS 32 months (95%CI, 14.28-49.72),
      respectively. INTERPRETATION: Results suggest that the combination of fulvestrant
      and goserelin offers promising activity in premenopausal patients and further
      investigation is warranted.

PMID- 22459765
TI  - The Early Aurignacian human remains from La Quina-Aval (France).
AB  - There is a dearth of diagnostic human remains securely associated with the Early
      Aurignacian of western Europe, despite the presence of similarly aged early
      modern human remains from further east. One small and fragmentary sample of such
      remains consists of the two partial immature mandibles plus teeth from the Early
      Aurignacian of La Quina-Aval, Charente, France. The La Quina-Aval 4 mandible
      exhibits a prominent anterior symphyseal tuber symphyseos on a vertical symphysis
      and a narrow anterior dental arcade, both features of early modern humans. The
      dental remains from La Quina-Aval 1 to 4 (a dm(1), 2 dm(2), a P(4) and a P(4))
      are unexceptional in size and present occlusal configurations that combine early
      modern human features with a few retained ancestral ones. Securely dated to ~33
      ka (14)C BP (~38 ka cal BP), these remains serve to confirm the association of
      early modern humans with the Early Aurignacian in western Europe.

PMID- 22459766
TI  - Sex at Sterkfontein: 'Mrs. Ples' is still an adult female.
AB  - The important question of whether the Australopithecus africanus hypodigm is
      taxonomically heterogeneous revolves largely around the interpretation of the
      morphological variation exhibited by the fossils from Sterkfontein. The sex
      assignment of these specimens is a critical component in the evaluation of their
      morphological variability. The Sts 5 cranium is pivotal in this regard because it
      is the most complete and undistorted specimen attributed to A. africanus.
      Although it has traditionally been regarded as an adult female, this view has
      been challenged. In particular, it has been argued recently that Sts 5 is a
      juvenile and that this, together with alveolar bone loss that has supposedly
      reduced the size of the canine socket, has led to its misinterpretation as a
      female. Virtual reconstruction of the M(3) roots (and/or alveoli) contradicts
      arguments that these teeth were erupting at the time of death. Regardless, canine
      emergence and root completion are well ahead of M(3) development in juvenile
      australopiths from Sterkfontein. Thus, even if the M(3) root of Sts 5 was
      incomplete, its canine root would have been fully formed. Measurements of palate
      depth indicate that the alveolar margins of Sts 5 have not suffered from much (if
      any) bone loss in the region of the C/P(3); any additional bone would result in a
      palate of truly exceptional depth. Therefore, the dimensions of the canine
      alveolus of Sts 5 can be regarded as proxies for those of the canine root. The
      canine root of Sts 5 is among the smallest recorded for any Sterkfontein
      australopith, which provides strong support for Robert Broom's initial
      attribution of sex to this specimen. There is no evidence to contradict the
      assertion that 'Mrs. Ples' is an adult female.

PMID- 22459764
TI  - Alterations of TP53 are associated with a poor outcome for patients with
      hepatocellular carcinoma: evidence from a systematic review and meta-analysis.
AB  - BACKGROUND: The prognostic significance of p53 aberration in hepatocellular
      carcinoma (HCC) remains inconclusive. This systematic review and meta-analysis
      aimed to provide comprehensive evidence on the association of p53 alterations
      with recurrence-free survival (RFS) and overall survival (OS) in HCC patients.
      METHODS: Systematic literature searches were conducted until July 2010. Meta
      analysis was performed to estimate prognostic effects of p53 alterations on
      patient outcomes in HCC. Sensitivity and subgroup analyses were also conducted in
      the meta-analysis. RESULTS: Thirty-seven studies (7 tumour p53 mutation, 23
      tumour p53 expression and 7 serum anti-p53 antibodies) were included in the
      systematic review and meta-analysis. The average percentages of p53 mutation, p53
      expression upregulation and anti-p53 antibody level elevation in HCC patients
      were 31.5%, 35.0% and 23.8%, respectively. Tumour p53 alterations were associated
      significantly with poor patient outcomes in HCC: the summary hazard ratio (HR) of
      mutant p53 versus wild type p53 phenotype was 2.58 [95% confidence interval (CI):
      1.96-3.41] for OS and 3.19 [95% CI: 2.21-4.60] for RFS, respectively; and the
      summary HR of upregulated p53 expression versus low/undetectable p53 expression
      was 1.68 [95% CI: 1.49-1.90] for OS and 1.89 [95% CI: 1.34-2.66] for RFS,
      respectively. However, elevated serum anti-p53 antibody was only associated with
      poor OS in HCC group with a high proportion of (>= 50%) of hepatitis C virus
      (HCV) infection [HR: 1.92; 95% CI: 1.30-2.85]. Moreover, sensitivity analyses
      showed that the results of meta-analyses were not altered. CONCLUSION: HCC
      patients with p53 mutation and upregulated expression in tumour tissue have a
      shorter OS and RFS than patients with wild type p53 and low/undetectable p53
      expression. However, the prognostic value of serum anti-p53 antibody is required
      to be further examined.

PMID- 22459768
TI  - Gene expression profiling to dissect the complexity of cancer biology: pitfalls
      and promise.
AB  - Despite advances in chemotherapy, hormone therapy and radiotherapy, not all
      cancer patients respond favorably to treatment. However, progress in
      understanding the mechanisms of malignant diseases and the mode of action of
      therapies are opening opportunities to match treatment to specific patient
      subpopulations, paving the way for personalized medicine. In this context, high
      throughput technologies that have been developed to determine gene expression
      profiles potentially offer an effective tool for dissecting the biology of cancer
      pathologies, for identifying candidate molecules for the development of new
      drugs, and for identifying individual patients who are more likely to respond
      favorably to a given therapy. Here, we overview and discuss the robustness of the
      deployment of these technologies in these contexts. We conclude that while these
      technologies are useful for target identification, there are limitations to their
      use in understanding cancer biology and in routine clinical application.

PMID- 22459769
TI  - Lung resection in hematologic patients with pulmonary invasive fungal disease.
AB  - BACKGROUND: Pulmonary invasive fungal disease is a frequent complication in
      patients with hematologic malignancies. Surgical resection in addition to
      antifungal therapy is an option for selected cases but often feared because of
      immunosuppression. METHODS: We analyzed the outcome of 71 patients undergoing
      lung resection for pulmonary invasive fungal disease. Most patients had leukemia,
      44 underwent high-dose chemotherapy, and 18 underwent stem cell transplantation.
      RESULTS: On the day of surgery, 44 patients were neutropenic, and 41 had a
      platelet count < 50 * 109/L. Forty-five nonanatomic (atypical) resections and 26
      lobectomies were performed. Fungal infection was histologically proven in 53
      patients. Reoperation was needed in four patients (bronchial stump dehiscence,
      persistent air leak, chylothorax, and seroma). Minor complications at the site of
      surgery occurred in 14 patients. In only two, there was an uncontrolled
      disseminated fungal infection. Overall, mortality at 30 days was 7% (five of 71).
      Long-term survival was mainly influenced by the underlying hematologic disease.
      CONCLUSIONS: Lung resection is a therapeutic option for hematologic patients with
      pulmonary fungal infection. Despite immunosuppression, the perioperative
      morbidity and mortality is acceptable, and, therefore, the prognosis is not
      determined by the surgical intervention.

PMID- 22459770
TI  - Pulmonary Langerhans cell histiocytosis-associated pulmonary hypertension:
      clinical characteristics and impact of pulmonary arterial hypertension therapies.
AB  - BACKGROUND: Precapillary pulmonary hypertension (PH) is a complication of
      pulmonary Langerhans cell histiocytosis (PLCH) associated with increased
      mortality. However, outcomes and efficacy of pulmonary arterial hypertension
      (PAH) therapies in patients with PH complicating PLCH(PLCH-PH) remain unknown.
      METHODS: Consecutive patients with PLCH with PH confirmed by right-sided heart
      catheterization were included in the study. Characteristics at baseline and
      during follow-up as well as survival were analyzed. RESULTS: Twenty-nine patients
      were studied. Baseline characteristics of patients with PLCH-PH wereas follows:
      83% of patients in World Health Organization (WHO) functional class III to IV,
      mean 6-min walk distance of 355 +/-95 m, mean pulmonary arterial pressure (mPAP)
      of 45 +/-14 mm Hg,cardiac index of 3.2+/- 0.9 L/min/m 2 , and pulmonary vascular
      resistance (PVR) of 555 +/-253 dyne/s/cm 5. Use of PAH therapy in 12 patients was
      followed by an improvement in mPAP (56+/-14 mm Hg and 45+/-12 mm Hg, P 5 .03) and
      PVR (701+/-239 dyne/s/cm 5 and 469+/-210 dyne/s/cm 5 , P = .01) between baseline
      and follow-up evaluations. No significant oxygen worsening was observed in the
      treated group. The 1-, 3-, and 5-year survival estimates of the 29 patients were
      96%, 92%, and 73%,respectively. Except a trend toward a better survival rate
      associated with the use of PAH therapy,WHO functional class was the only variable
      significantly associated with death. CONCLUSIONS: In this group of patients, PAH
      therapies improved hemodynamics without oxygen worsening or pulmonary edema. WHO
      functional class was the only prognostic factor identified.Prospective clinical
      trials focusing on this population of patients are warranted

PMID- 22459771
TI  - Response to add-on inhaled corticosteroids in COPD based on airway
      hyperresponsiveness to mannitol.
AB  - BACKGROUND: The use of inhaled corticosteroids in mild to moderate COPD is
      controversial. The aim of this study was to determine whether airway
      hyperresponsiveness to mannitol might identify patients who are likely to respond
      to add-on inhaled corticosteroids. METHODS: Ninety subjects with mild to moderate
      COPD were recruited and 68 subsequently randomized in a double-blind manner to
      receive inhaled budesonide (1,600 MUg/d, n = 31) or placebo (n = 37) for 3
      months. Thirty-eight subjects had airway hyperresponsiveness to mannitol (17
      received budesonide, 21 placebo). All subjects received tiotropium throughout the
      study, including 4 weeks before randomization. Spirometry, quality of life (St.
      George Respiratory Questionnaire), degree of dyspnea, airway responsiveness to
      mannitol, and exhaled nitric oxide were assessed at week 0 (recruitment), week 4
      (baseline prior to randomization), and week 16 (posttreatment). RESULTS: Compared
      with placebo, budesonide was associated with improved quality of life in subjects
      showing airway hyperresponsiveness to mannitol (difference of changes in quality
      of life score between randomization and study completion, -9.1; 95% CI, -15.8 to 
      2.3; P < .01). Treatment with inhaled budesonide also led to a reduction in
      airway responsiveness to mannitol compared with placebo (difference in log10
      response-dose ratio, -0.3; 95% CI, -0.6 to -0.04; P < .01). However,
      postrandomization changes in FEV1 % predicted, quality of life, and exhaled
      nitric oxide showed no difference between budesonide and placebo. CONCLUSIONS: In
      subjects with mild to moderate COPD and airway hyperresponsiveness to mannitol,
      quality of life and airway responsiveness improved after treatment with inhaled
      corticosteroids added to long-acting bronchodilator therapy.

PMID- 22459772
TI  - Intrapleural fibrinolytic therapy for treatment of adult parapneumonic effusions
      and empyemas: a systematic review and meta-analysis.
AB  - BACKGROUND: The purpose of our study was to conduct a systematic review and meta
      analysis of all randomized controlled trials to date comparing fibrinolytics with
      placebo to clarify their current role in the management of parapneumonic
      effusions and empyemas. METHODS: MEDLINE, EMBASE, PapersFirst, and the Cochrane
      Collaboration and the Cochrane Register of controlled trials were searched. All
      searches were inclusive as of October 2011. Two investigators independently
      reviewed articles and extracted data. Quality was assessed with the Cochrane
      concealment of allocation approach and the Jadad criteria. RESULTS: Seven
      randomized controlled studies (total number of patients, 801) comparing
      fibrinolytic therapy with placebo were included in the meta-analysis.
      Fibrinolytic therapy was beneficial for the outcomes of treatment failure
      (surgical intervention or death) (risk ratio [RR], 0.50; 95% CI, 0.28-0.87) and
      surgical intervention alone (RR, 0.61; 95% CI, 0.45-0.82). There was no
      difference in mean duration of hospital stay (standard mean difference, -0.69;
      95% CI, -1.54-0.16) or death (RR, 1.14; 95% CI, 0.74-1.74). CONCLUSIONS: This
      meta-analysis does reveal that fibrinolytic therapy is potentially beneficial in
      the management of parapneumonic effusions and empyemas in the adult population.
      Although there is insufficient evidence to support the routine use of this
      therapy for all parapneumonic effusions/empyemas, fibrinolytic therapy may be
      considered in patients with loculated pleural effusions, because it may prevent
      the need for surgical intervention. Further randomized controlled trials with
      adequate power are needed to definitively address the effect of fibrinolytics and
      the combination of fibrinolytics and deoxyribonuclease on the clinical outcomes
      outlined in this analysis in patients with parapneumonic effusions/empyemas.

PMID- 22459773
TI  - A multicenter study on chronic cough in children : burden and etiologies based on
      a standardized management pathway.
AB  - BACKGROUND: While the burden of chronic cough in children has been documented,
      etiologic factors across multiple settings and age have not been described. In
      children with chronic cough, we aimed (1) to evaluate the burden and etiologies
      using a standard management pathway in various settings, and (2) to determine the
      influence of age and setting on disease burden and etiologies and etiology on
      disease burden. We hypothesized that the etiology, but not the burden, of chronic
      cough in children is dependent on the clinical setting and age. METHODS: From
      five major hospitals and three rural-remote clinics, 346 children (mean age 4.5
      years) newly referred with chronic cough (> 4 weeks) were prospectively managed
      in accordance with an evidence-based cough algorithm. We used a priori
      definitions, timeframes, and validated outcome measures (parent-proxy cough
      specific quality of life [PC-QOL], a generic QOL [pediatric quality of life
      (PedsQL)], and cough diary). RESULTS: The burden of chronic cough (PC-QOL, cough
      duration) significantly differed between settings (P = .014, 0.021,
      respectively), but was not influenced by age or etiology. PC-QOL and PedsQL did
      not correlate with age. The frequency of etiologies was significantly different
      in dissimilar settings (P = .0001); 17.6% of children had a serious underlying
      diagnosis (bronchiectasis, aspiration, cystic fibrosis). Except for protracted
      bacterial bronchitis, the frequency of other common diagnoses (asthma,
      bronchiectasis, resolved without specific-diagnosis) was similar across age
      categories. CONCLUSIONS: The high burden of cough is independent of children's
      age and etiology but dependent on clinical setting. Irrespective of setting and
      age, children with chronic cough should be carefully evaluated and child-specific
      evidence-based algorithms used.

PMID- 22459774
TI  - Effects of lecithinized superoxide dismutase and/or pirfenidone against bleomycin
      induced pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) involves lung injury induced by
      reactive oxygen species (ROS), such as superoxide anion, and fibrosis. Superoxide
      dismutase (SOD) catalyses the dismutation of superoxide anion to hydrogen
      peroxide. We recently reported that inhalation of lecithinized SOD (PC-SOD)
      ameliorated bleomycin-induced pulmonary fibrosis. We here studied effects of PC
      SOD on bleomycin-induced pulmonary fibrosis and lung dysfunction and compared the
      results to those obtained with pirfenidone, a newly developed drug for IPF.
      METHODS: Lung mechanics (elastance) and respiratory function (FVC) were assessed
      using a computer-controlled ventilator. Respiratory function was evaluated by
      monitoring percutaneous arterial oxygen saturation (SpO2). RESULTS: Both
      inhalation of PC-SOD and oral administration of pirfenidone ameliorated bleomycin
      induced pulmonary fibrosis and changes in lung mechanics. Administration of
      bleomycin produced a decrease in both FVC and SpO2. PC-SOD treatment led to
      significant recovery of both parameters, whereas pirfenidone improved only SpO2.
      PC-SOD suppressed the bleomycin-induced pulmonary inflammatory response and
      production of superoxide anions in the lung more effectively than pirfenidone.
      Furthermore, both PC-SOD and pirfenidone produced a therapeutic effect even when
      the drug was administered after the development of fibrosis. PC-SOD and
      pirfenidone also produced a synergistic therapeutic effect. CONCLUSIONS: These
      results suggest that the superior activity of PC-SOD to pirfenidone against
      bleomycin-induced pulmonary fibrosis and lung dysfunction is due to its unique
      antioxidant activity. We propose that treatment of IPF with a combination of PC
      SOD and pirfenidone could be therapeutically beneficial.

PMID- 22459775
TI  - The relationship between pulmonary emphysema and kidney function in smokers.
AB  - BACKGROUND: It has been reported that the prevalence of kidney dysfunction may be
      increased in patients exposed to tobacco with airflow obstruction. We
      hypothesized that kidney dysfunction would associate with emphysema rather than
      with airflow obstruction measured by the FEV1. METHODS: Five hundred eight
      current and former smokers completed a chest CT scan, pulmonary function tests,
      medical questionnaires, and measurement of serum creatinine. Glomerular
      filtration rates (eGFRs) were estimated using the method of the Chronic Kidney
      Disease Epidemiology Collaboration. Quantitative determinants of emphysema and
      airway dimension were measured from multidetector chest CT scans. RESULTS: The
      mean age was 66 +/- 7 years, and mean eGFR was 101 +/- 22 mL/min/1.73 m2.
      Univariate and multivariate analysis showed a significant association between
      radiographically measured emphysema and eGFR: Participants with 10% more
      emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m2 (P = .01), independent
      of airflow obstruction (FEV1), age, sex, race, height, BMI, diabetes mellitus,
      hypertension, coronary artery disease, patient-reported dyspnea, pack-years of
      smoking, and current smoking. There was no association between eGFR and either
      FEV1 or quantitative CT scan measures of airway dimension. CONCLUSIONS: More
      severe emphysema, rather than airflow obstruction, is associated with kidney
      dysfunction in tobacco smokers, independent of common risk factors for kidney
      disease. This finding adds to recent observations of associations between
      emphysema and comorbidities of COPD, including osteoporosis and lung cancer,
      which are independent of the traditional measure of reduced FEV1. The mechanisms
      and clinical implications of kidney dysfunction in patients with emphysema need
      further investigation.

PMID- 22459776
TI  - Sleep-disordered breathing and caffeine consumption: results of a community-based
      study.
AB  - BACKGROUND: Sleepiness is one of the most burdensome symptoms of sleep-disordered
      breathing (SDB). While caffeine is frequently used to avert sleepiness, the
      association between SDB and caffeine use has not been thoroughly explored. The
      current study examined whether SDB is associated with caffeine consumption and if
      factors such as sex, age, and daytime sleepiness explain or modify the
      association. METHODS: Data from the Sleep Heart Health Study, a community-based
      study on the consequences of SDB, were used to characterize the association
      between SDB and caffeine intake. SDB was assessed with full-montage
      polysomnography. Caffeine use was quantified as the number of cans of soda or the
      cups of coffee or tea consumed daily. The Epworth Sleepiness Scale was used to
      assess daytime sleepiness. Multivariable negative binomial regression models were
      used to characterize the independent association between SDB and caffeine use.
      RESULTS: Caffeinated soda, but not tea or coffee, intake was independently
      associated with SDB severity. Compared with participants without SDB, the
      relative ratios for caffeinated soda consumption in women with mild, moderate,
      and severe SDB were 1.20 (CI, 1.03-1.41), 1.46 (CI, 1.14-1.87), and 1.73 (CI,
      1.23-2.42), respectively. For men, an association was only noted with severe SDB
      and caffeinated soda use. Age did not modify the SDB-caffeine association, and
      sleepiness could not explain the observed associations. CONCLUSIONS: SDB is
      independently associated with caffeinated soda use in the general community.
      Identifying excessive caffeine used in SDB has potential significance given the
      cardiovascular effects of caffeine and untreated SDB.

PMID- 22459778
TI  - The global burden of atrial fibrillation and stroke: a systematic review of the
      epidemiology of atrial fibrillation in regions outside North America and Europe.
AB  - BACKGROUND: Although atrial fibrillation (AF) is accepted as the most common
      sustained cardiac arrhythmia, most published epidemiologic studies focus on
      predominantly white populations in North America or Europe, and information on AF
      in nonwhite populations is scarce. The objective of this study was to undertake a
      systematic review of the published literature on the epidemiology of AF in other
      regions. METHODS: Systematic literature searches (MEDLINE; 1990-2010) identified
      epidemiologic studies reporting on the prevalence or incidence of AF, stroke in
      AF, risk factors for AF, or the use of antithrombotic therapy in countries
      outside North America and Europe. This report presents a descriptive analysis of
      the data; no meta-analysis was planned. RESULTS: Many of the 38 articles
      identified were from the Far East, although Australia, New Zealand, the Middle
      East, and South America were also represented. The reported prevalence of AF
      varied among countries, with different ranges in community- and hospital-based
      studies (0.1%-4% and 2.8%-14%, respectively). The use of anticoagulant therapy
      varied widely among countries and studies, as did the reported prevalence of
      stroke in patients with AF (2.8%-24.2%). CONCLUSIONS: High-quality epidemiologic
      studies are clearly required to improve understanding of the worldwide burden of
      AF and stroke in AF. Major improvements in the provision of thromboprophylaxis
      are also needed in many countries, given the high proportion of untreated
      patients who are, hence, at risk of stroke.

PMID- 22459777
TI  - Pulmonary embolism: the weekend effect.
AB  - BACKGROUND: Pulmonary embolism is a common, often fatal condition that requires
      timely recognition and rapid institution of therapy. Previous studies have
      documented worse outcomes for weekend admissions for a variety of time-sensitive
      medical conditions. This phenomenon has not been clearly demonstrated for
      pulmonary embolism. METHODS: We used the Healthcare Cost and Utilization Project
      Nationwide Inpatient Sample for the years 2000 to 2008 to identify people with a
      principal discharge diagnosis of pulmonary embolism. We classified admissions as
      weekend if they occurred between midnight Friday and midnight Sunday. We compared
      all-cause in-hospital mortality between weekend and weekday admissions and
      investigated the timing of inferior vena cava (IVC) filter placement and
      thrombolytic infusion as potential explanations for differences in mortality.
      RESULTS: Unadjusted mortality was higher for weekend admissions than weekday
      admissions (OR, 1.19; 95% CI, 1.13-1.24). This increase in mortality remained
      statistically significant after controlling for potential confounding variables
      (OR, 1.17; 95% CI, 1.11-1.22). Among patients who received an IVC filter, a
      larger proportion of those admitted on a weekday than on the weekend received it
      on their first hospital day (38% vs 29%, P < .001). The timing of thrombolytic
      therapy did not differ between weekday and weekend admissions. CONCLUSIONS:
      Weekend admissions for pulmonary embolism were associated with higher mortality
      than weekday admissions. Our finding that IVC filter placement occurred later in
      the hospital course for patients admitted on weekends with pulmonary embolism
      suggests differences in the timeliness of diagnosis and treatment between weekday
      and weekend admissions. Regardless of cause, physicians should be aware that
      weekend admissions for pulmonary embolism have a 20% increased risk of death and
      warrant closer attention than provided during the week.

PMID- 22459779
TI  - Complete unilateral vs partial bilateral endoscopic lung volume reduction in
      patients with bilateral lung emphysema.
AB  - BACKGROUND: Intrabronchial valve placement for endoscopic lung volume reduction
      is used for patients with severe lung emphysema. Different treatment approaches
      are unilateral valve placement with the goal of complete occlusion and subsequent
      atelectasis leading to true volume reduction vs bilateral partial closure aiming
      for redistribution of ventilation but avoiding atelectasis. In this prospective
      pilot trial, we compared the efficacy of these treatment approaches. METHODS:
      Patients with severe bilateral heterogeneous emphysema were randomized to two
      groups. In the fi rst group, patients received unilateral valves aiming for total
      occlusion of one lobe. In the other group, valves were placed in two
      contralateral lobes with incomplete closure. In all cases, one-way valves were
      placed via a flexible bronchoscope. Patients were followed at 30 and 90 days, end
      points being change in pulmonary function tests (PFTs), 6-min walk distance
      (6MWD),and dyspnea score as measured by the modified Medical Research Council
      (mMRC) dyspnea score,as well as quality of life as measured by the St. George
      Respiratory Questionnaire (SGRQ). RESULTS: Twenty-two patients were treated in
      this study, 11 patients in each arm. At 30 days and 90 days, significant
      differences were seen in PFT and 6MWD, as well as in mMRC and SGRQ scores, in
      favor of unilateral treatment. At 90 days, FEV 1 was improved by 21.4% 10.7% in
      this group, but not in the bilateral group ( 2 0.03% 13.9%, P 5 .002). One
      patient in the unilateral group experienced a pneumothorax, and two patients in
      the bilateral group were treated for transient respiratory failure. CONCLUSIONS:
      Unilateral intrabronchial valve placement with complete occlusion appears
      superior to bilateral partial occlusion.

PMID- 22459780
TI  - The effect of marital status on the presentation and outcomes of elderly male
      veterans hospitalized for pneumonia.
AB  - BACKGROUND: Although marital status has been shown to affect the outcomes of many
      conditions, there are limited data on the relationships between marital status
      and the presentation and outcomes of pneumonia. METHODS: We used Veterans Affairs
      administrative databases to identify a retrospective cohort of male veterans age
      >= 65 years hospitalized for pneumonia between 2002 and 2007. We assessed
      unadjusted and adjusted associations between marital status and mortality,
      hospital length of stay, and readmission to the hospital using generalized linear
      mixed-effect models with admitting hospital as a random effect and adjusted for
      baseline patient characteristics. RESULTS: There were 48,635 patients (26,558
      married and 22,077 unmarried) in the study. Married men had a slightly higher
      Charlson comorbidity score (3.0 vs 2.8, P < .0001) but were less likely to
      require ICU admission, ventilator support, and vasopressor treatment during the
      first 48 h of hospitalization. Married patients had significantly lower crude and
      adjusted in-hospital mortality (9.4% vs 10.6%; adjusted OR, 0.87; 95% CI, 0.81
      0.93) and mortality during the 90 days after hospital discharge (14.7% vs 16.0%;
      adjusted OR, 0.92; 95% CI, 0.88-0.98). Their adjusted incidence rate ratio length
      of stay was also lower (0.92; 95% CI, 0.91-0.92). CONCLUSIONS: Unmarried elderly
      men admitted to the hospital with pneumonia have a higher risk of in-hospital and
      postdischarge mortality, despite having a lower degree of comorbidity. Although
      marital status may be a surrogate marker for other predictors, it is an easily
      identifiable one. These results should be considered by those responsible for
      care-transition decisions for patients hospitalized with pneumonia.

PMID- 22459782
TI  - Inflammatory and satellite cells in the quadriceps of patients with COPD and
      response to resistance training.
AB  - BACKGROUND: Quadriceps dysfunction in COPD may be mediated by inflammatory
      mechanisms or impaired satellite cell function. Resistance training is of proven
      efficacy in these patients, but data on muscle inflammatory and satellite cell
      response to resistance exercise in COPD are lacking.We aimed to examine the
      inflammatory and satellite cell profile of the quadriceps in patients with COPD
      and healthy control subjects at rest and after acute and chronic resistance
      exercise. METHODS: Seventeen patients with COPD and 10 healthy control subjects
      underwent 8 weeks ofbilateral lower-limb, high-intensity resistance training,
      thrice weekly, on an isokinetic dynamometer.Quadriceps muscle biopsy specimens
      from the dominant thigh were obtained at baseline,24 h following the fi rst
      exercise bout, and after 8 weeks 24 h after the last exercise bout.
      Glycolmethacrylate-embedded muscle biopsy specimens were analyzed using
      immunohistochemistry to identify neutrophils, macrophages, and satellite cells.
      RESULTS: Neutrophils were significantly elevated in the quadriceps of patients
      with COPD at baseline compared with healthy control subjects ( P 5 .03).
      Inflammatory cells were increased significantly at 24 h in both groups but were
      similar to baseline values at week 8, with no difference detectable between
      healthy control subjects and patients with COPD. Satellite cell numbers were
      comparable between patients and control subjects at baseline, tended to increase
      at 24 h, and remained elevated at week 8. CONCLUSIONS: Inflammatory cells are
      elevated in the resting quadriceps of patients with COPD. Acute resistance
      exercise leads to an inflammatory myositis, which is attenuated with regular
      training. Satellite cells in patients and control subjects are comparable and are
      increased in response to exercise. TRIAL REGISTRY: ISRCTN Register ; No.:
      ISRCTN22764439; URL: www.controlled-trials.com.

PMID- 22459781
TI  - Volumetric optical frequency domain imaging of pulmonary pathology with precise
      correlation to histopathology.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related mortality.
      Radiology and bronchoscopy techniques do not have the necessary resolution to
      evaluate lung lesions on the microscopic scale, which is critical for diagnosis.
      Bronchial biopsy specimens can be limited by sampling error and small size.
      Optical frequency domain imaging (OFDI) provides volumetric views of tissue
      microstructure at near-histologic resolution and may be useful for evaluating
      pulmonary lesions to increase diagnostic accuracy. Bronchoscopic OFDI has been
      evaluated in vivo, but a lack of correlated histopathology has limited the
      ability to develop accurate image interpretation criteria. METHODS: We performed
      OFDI through two approaches (airway-centered and parenchymal imaging) in 22 ex
      vivo lung specimens, using tissue dye to precisely correlate imaging and
      histology. RESULTS: OFDI of normal airway allowed visualization of epithelium,
      lamina propria, cartilage, and alveolar attachments. Carcinomas exhibited
      architectural disarray, loss of normal airway and alveolar structure, and rapid
      light attenuation. Squamous cell carcinomas showed nested architecture. Atypical
      glandular formation was appreciated in adenocarcinomas, and uniform trabecular
      gland formation was seen in salivary gland carcinomas. Mucinous adenocarcinomas
      showed alveolar wall thickening with intraalveolar mucin. Interstitial fibrosis
      was visualized as signal-dense tissue, with an interstitial distribution in mild
      interstitial fibrotic disease and a diffuse subpleural pattern with cystic space
      formation in usual interstitial pneumonitis. CONCLUSIONS: To our knowledge, this
      study is the first demonstration of volumetric OFDI with precise correlation to
      histopathology in lung pathology. We anticipate that OFDI may play a role in
      assessing airway and parenchymal pathology, providing fresh insights into the
      volumetric features of pulmonary disease.

PMID- 22459783
TI  - Childhood infections and the risk of asthma: a longitudinal study over 37 years.
AB  - BACKGROUND: Few studies have examined common childhood infections and adult
      asthma. We examined associations between childhood infectious diseases, childhood
      pneumonia, and current, persisting, and incident asthma to middle age. METHODS:
      We analyzed data from the Tasmanian Longitudinal Health Study (TAHS). A history
      of pneumonia was ascertained from their parents when the TAHS participants were 7
      years old. Measles, rubella, mumps, chickenpox, diphtheria, and pertussis were
      identified from school medical records. Associations with current, persisting, or
      incident asthma were examined using regression techniques. RESULTS: Greater
      infectious diseases load was negatively associated with persisting asthma at all
      ages. Individually, pertussis (adjusted OR [aOR], 0.53; 95% CI, 0.28-1.00) was
      negatively associated with asthma persisting to age 13 years, chickenpox (aOR,
      0.58; 95% CI, 0.38-0.88) was negatively associated with asthma persisting to age
      32 years, and rubella was negatively associated with asthma persisting to ages 32
      (aOR, 0.61; 95% CI, 0.31-0.96) and 44 years (aOR 0.53; 95% CI, 0.35-0.82).
      Pertussis was associated with preadolescent incident asthma (adjusted hazard
      ratio [aHR], 1.80; 95% CI, 1.10-2.96), whereas measles was associated with
      adolescent incident asthma (aHR, 1.66; 1.06-2.56). Childhood pneumonia was
      associated with current asthma at ages 7 (aOR, 3.12; 95% CI, 2.61-3.75) and 13
      years (aOR, 1.32; 95% CI, 1.00-1.75), an association stronger in those without
      than those with eczema (aOR, 3.46; 95% CI, 2.83-4.24 vs aOR, 2.08; 95% CI, 1.38
      3.12). CONCLUSIONS: Overall, childhood infectious diseases protected against
      asthma persisting in later life, but pertussis and measles were associated with
      new-onset asthma after childhood. Measles and pertussis immunization might lead
      to a reduction in incident asthma in later life.

PMID- 22459784
TI  - Sleep disturbances among soldiers with combat-related traumatic brain injury.
AB  - BACKGROUND: Sleep complaints are common among patients with traumatic brain
      injury. Evaluation of this population is confounded by polypharmacy and comorbid
      disease, with few studies addressing combat-related injuries. The aim of this
      study was to assess the prevalence of sleep disorders among soldiers who
      sustained combat-related traumatic brain injury. METHODS: The study design was a
      retrospective review of soldiers returning from combat with mild to moderate
      traumatic brain injury. All underwent comprehensive sleep evaluations. We
      determined the prevalence of sleep complaints and disorders in this population
      and assessed demographics, mechanism of injury, medication use, comorbid
      psychiatric disease, and polysomnographic findings to identify variables that
      correlated with the development of specific sleep disorders. RESULTS: Of 116
      consecutive patients, 96.6% were men (mean age, 31.1 +/- 9.8 years; mean BMI,
      27.8 +/- 4.1 kg/m2), and 29.5% and 70.5% sustained blunt and blast injuries,
      respectively. Nearly all (97.4%) reported sleep complaints. Hypersomnia and sleep
      fragmentation were reported in 85.2% and 54.3%, respectively. Obstructive sleep
      apnea syndrome (OSAS) was found in 34.5%, and 55.2% had insomnia. Patients with
      blast injuries developed more anxiety (50.6% vs 20.0%, P = .002) and insomnia
      (63% vs 40%, P = .02), whereas patients with blunt trauma had significantly more
      OSAS (54.3% vs 25.9%, P = .003). In multivariate analysis, blunt trauma was a
      significant predictor of OSAS (OR, 3.09; 95% CI, 1.02-9.38; P = .047).
      CONCLUSIONS: Sleep disruption is common following traumatic brain injury, and the
      majority of patients develop a chronic sleep disorder. It appears that sleep
      disturbances may be influenced by the mechanism of injury in those with combat
      related traumatic brain injury, with blunt injury potentially predicting the
      development of OSAS.

PMID- 22459786
TI  - Cyclothymic disorder: a critical review.
AB  - Cyclothymic disorder is a subtype of bipolar disorder included in the Diagnostic
      and Statistical Manual of Mental Disorders since 1980, but largely neglected in
      research. Additionally, it is rarely diagnosed clinically, in spite of evidence
      that it may be the most prevalent form of bipolar disorder. Neglect has
      contributed to confusion about the diagnosis and clinical presentation of
      cyclothymic disorder. Its status as a mood disorder is also ambiguous due to
      overlap in terminology and symptoms with temperament and personality disorders.
      Subthreshold bipolar disorder appears more prevalent among young people than
      previously thought, and follows a range of trajectories from remission to
      escalation-raising questions about risk factors and traits associated with the
      varied course. Cyclothymic disorder may be an important diathesis for major mood
      disorders. Constructs such as cyclothymic disorder link major mood disorder and
      peri-clinical fluctuations of mood, thus warranting a prominent role in
      dimensional models of mood and psychopathology. Current evidence indicates that
      cyclothymic disorder is a prevalent and highly impairing disorder on the bipolar
      spectrum, with the potential to make unique contributions to our understanding of
      the risk factors and outcomes associated with bipolar disorder. The inclusion of
      cyclothymic disorder in future research studies is essential to accurate
      diagnosis and effective treatment for the full spectrum of bipolar disorder, as
      well as understanding the developmental trajectory of bipolar spectrum disorders.

PMID- 22459785
TI  - Parenting in adults with attention-deficit/hyperactivity disorder (ADHD).
AB  - Although the validity of adult ADHD is well established and research has
      identified a variety of impairments associated with the condition in adults,
      study of how ADHD impacts an adult's ability to parent has been relatively
      neglected. Parenting is a particularly important domain of functioning given the
      familial nature of the disorder and emerging evidence that parenting behaviors
      play a role in the development or maintenance of child ADHD symptoms, comorbid
      psychopathologies, and other associated difficulties. In this paper, we focus on
      three broad categories of cognitive dysfunction proposed across models of ADHD -
      cognitive processes (e.g., working memory, planning, and inhibitory control),
      self-regulation deficits (e.g., self-monitoring of performance to detect errors
      or the need for regulation of behavior and/or emotions), and motivational or
      arousal difficulties (e.g., response to incentives, delay aversion). We consider
      how these deficits may lead to impairments in the parenting behaviors of
      effective behavioral control and emotional responsiveness, and review the
      available evidence regarding parenting in adults with ADHD symptoms. We conclude
      by noting the limitations in existing studies, and argue for further research
      that is theoretically grounded in how core deficits of ADHD may be related to
      dimensions of parenting. The implications of an improved understanding of how
      ADHD impacts parenting for the development of early intervention or prevention
      programs are outlined.

PMID- 22459787
TI  - Contributions of emotional prosody comprehension deficits to the formation of
      auditory verbal hallucinations in schizophrenia.
AB  - Deficits in emotional processing have been widely described in schizophrenia.
      Associations of positive symptoms with poor emotional prosody comprehension (EPC)
      have been reported at the phenomenological, behavioral, and neural levels. This
      review focuses on the relation between emotional processing deficits and auditory
      verbal hallucinations (AVH). We explore the possibility that the relation between
      AVH and EPC in schizophrenia might be mediated by the disruption of a common
      mechanism intrinsic to auditory processing, and that, moreover, prosodic feature
      processing deficits play a pivotal role in the formation of AVH. The review
      concludes with proposing a mechanism by which AVH are constituted and showing how
      different aspects of our neuropsychological model can explain the constellation
      of subjective experiences which occur in relation to AVH.

PMID- 22459788
TI  - Effects of psychotherapy for anxiety in children and adolescents: a meta-analytic
      review.
AB  - This paper provides a comprehensive quantitative review of high quality
      randomized controlled trials of psychological therapies for anxiety disorders in
      children and young people. Using a systematic search for randomized controlled
      trials which included a control condition and reported data suitable for meta
      analysis, 55 studies were included. Eligible studies were rated for
      methodological quality and outcome data were extracted and analyzed using
      standard methods. Trial quality was variable, many studies were underpowered and
      adverse effects were rarely assessed; however, quality ratings were higher for
      more recently published studies. Most trials evaluated cognitive behavior therapy
      or behavior therapy and most recruited both children and adolescents.
      Psychological therapy for anxiety in children and young people was moderately
      effective overall, but effect sizes were small to medium when psychological
      therapy was compared to an active control condition. The effect size for non-CBT
      interventions was not significant. Parental involvement in therapy was not
      associated with differential effectiveness. Treatment targeted at specific
      anxiety disorders, individual psychotherapy, and psychotherapy with older
      children and adolescents had effect sizes which were larger than effect sizes for
      treatments targeting a range of anxiety disorders, group psychotherapy, and
      psychotherapy with younger children. Few studies included an effective follow-up.
      Future studies should follow CONSORT reporting standards, be adequately powered,
      and assess follow-up. Research trials are unlikely to address all important
      clinical questions around treatment delivery. Thus, careful assessment and
      formulation will remain an essential part of successful psychological treatment
      for anxiety in children and young people.

PMID- 22459789
TI  - How do we optimally conceptualize the heterogeneity within antisocial behavior?
      An argument for aggressive versus non-aggressive behavioral dimensions.
AB  - Extant research has highlighted meaningful distinctions in the correlates,
      developmental trajectories, and etiologies of physically aggressive (AGG) as
      compared to non-aggressive rule-breaking (RB) antisocial behavior. AGG is a
      highly heritable behavioral dimension that emerges in early childhood and
      exhibits specific ties to negative emotionality and executive dysfunction.
      Although the frequency of aggressive behaviors decreases after early childhood,
      those who are most aggressive early in life typically continue to aggress at
      relatively high rates across the lifespan. By contrast, RB demonstrates specific
      associations with impulsivity, is most frequent during adolescence, and evidences
      more moderate levels of stability and stronger environmental influences as
      compared to AGG. These etiological and developmental differences link up quite
      well to Moffitt's (1993) developmental taxonomy of antisocial behavior, providing
      a clear theoretical basis for examining differences between AGG and RB. Perhaps
      more importantly, however, the link between AGG/RB and Moffitt's taxonomy allows
      us to conceptualize her categorical taxonomy in dimensional terms, an important
      development given the recent emphasis on dimensional conceptualizations of
      psychopathology. Available evidence further indicates that neither AGG nor RB is
      redundant with callous-unemotional traits. The current review thus underscores
      the clear advantages of differentiating between AGG and RB when studying
      antisocial behavior.

PMID- 22459790
TI  - A review of the definitions of outcome used in the treatment of bulimia nervosa.
AB  - There are many terms used to describe treatment outcome for bulimia nervosa.
      However, the way such terms are conceptualised across various studies differs
      dramatically, making comparison of outcomes difficult. A consensus working
      definition of pivotal terms such as remission and recovery is important if
      treatments are to be adequately evaluated and clinical meaning derived for
      individuals with bulimia nervosa (BN). The central aim of the current review was
      to identify different definitions of remission and recovery and their utility in
      terms of client outcome after treatment for BN. Seventy one unique published
      treatment studies were identified that used 82 different outcome measures, of
      which 63 (77%) used behavioural outcomes only, with the most commonly used
      outcome (n=7 studies) being an abstinence of bingeing and vomiting for a 4 week
      period. The problems with the definitions of outcomes used to date are explored,
      and the implications of research in anorexia nervosa for forming consensus
      definitions of remission and recovery for BN will be examined. In addition, the
      review highlights the importance of considering the relationship between quality
      of life and outcome in assessing the "goodness of fit" of a definition of
      outcome.

PMID- 22459792
TI  - A systematic meta-analysis of the Stroop task in depression.
AB  - Despite the extensive use of the Emotional Stroop task in depression, only
      qualitative reviews have been produced to date, and these reviews conclude that
      Stroop performance in depression is equivocal. The present meta-analysis
      addressed the need to summarize the data quantitatively. A thorough search of the
      literature was conducted and 47 published studies and unpublished doctoral
      dissertations were included in the analyses. The meta-analysis revealed large and
      robust depression-related Stroop effects (e.g., for clinically depressed versus
      control participants on negative stimuli, g=.98, and on positive stimuli, g=.87).
      Although the effects did not reflect a strong emotion-congruent bias, they did
      distinguish among levels of depressive experience, in that greater levels of
      depression severity were associated with larger between-groups effect sizes.
      Moreover, these effects have been obtained without priming procedures, or the
      presentation of self-relevant or disorder-congruent stimuli. These findings
      challenge schema-based theories of the Emotional Stroop effect and predictions
      based on previous qualitative reviews of the literature. The findings also
      suggest that further comparative behavioural research on the depression-related
      Stroop effect, at least among clinically depressed populations, is not necessary.
      Future research should address questions about underlying mechanisms and focus on
      a more direct measure of depression-related attentional bias.

PMID- 22459793
TI  - The cost utility of reduction mammaplasty.

PMID- 22459791
TI  - Relations among posttraumatic stress disorder, comorbid major depression, and HPA
      function: a systematic review and meta-analysis.
AB  - Exposure to traumatic stress is associated with increased risk for posttraumatic
      stress disorder (PTSD) and alterations of hypothalamic-pituitary-adrenocortical
      (HPA) function. Research linking traumatic stress with HPA function in PTSD has
      been inconsistent, however, in part due to (a) the inclusion of trauma-exposed
      individuals without PTSD (TE) in control groups and (b) a failure to consider
      comorbid major depressive disorder (MDD) and moderating variables. This meta
      analysis of 47 studies (123 effect sizes, N=6008 individuals) revealed that daily
      cortisol output was lower for PTSD (d=-.36, SE=.15, p=.008) and PTSD+MDD (d=-.65,
      SE=.25, p=.008) groups relative to no trauma controls (NTC); TE and NTC groups
      did not differ significantly from each other. Afternoon/evening cortisol was
      lower in TE (d=-.25, SE=.09, p=.007) and PTSD (d=-.27, SE=.12, p=.021) groups and
      higher in PTSD+MDD groups (d=.49, SE=.24, p=.041) relative to NTC. Post-DST
      cortisol levels were lower in PTSD (d=-.40, SE=.12, p<.001), PTSD+MDD (d=-.65,
      SE=.14, p<.001), and TE groups (d=-.53, SE=.14, p<.001) relative to NTC. HPA
      effect sizes were moderated by age, sex, time since index event, and
      developmental timing of trauma exposure. These findings suggest that enhanced HPA
      feedback function may be a marker of trauma-exposure rather than a specific
      mechanism of vulnerability for PTSD, whereas lower daily cortisol output may be
      associated with PTSD in particular.

PMID- 22459794
TI  - Lower eyelid reconstruction in a paediatric face: a one-stage aesthetic approach
      using the versatile temporoparietal fascia flap.
AB  - There are many different lower eyelid reconstruction techniques defined in the
      literature. Almost all of the published techniques have been described on elderly
      patients and use upper eyelid, periorbital or facial tissues as donor sites.
      However, in case of a paediatric patient or a young adult who has a crease-free
      and scarless face, camouflage of the facial donor-site scar is usually
      impossible. In order to avoid possible facial donor-site scars and upper eyelid
      deformities, a technique which uses the temporoparietal fascia (TPF) flap as the
      framework of a new eyelid was used for the reconstruction of an adolescent
      patient's postoncologic defect. The inner side of the flap was covered with nasal
      septal chondromucosal graft and the external side was covered with a
      retroauricular full-thickness skin graft. Eighteen months of unproblematic follow
      up of this overlooked usage of the versatile TPF flap indicates that our
      technique has proved successful in terms of good functional and cosmetic outcome
      that is obtained at one stage.

PMID- 22459795
TI  - Pediatric orbital floor trapdoor fractures: outcomes and CT-based morphologic
      assessment of the inferior rectus muscle.
AB  - INTRODUCTION: Trauma to the pediatric orbit may produce a unique fracture in
      which entrapment of the periorbital tissue and/or inferior rectus muscle may
      occur due to a "trap-door" effect of the compliant orbital floor. This study was
      designed to assess the outcome following the surgical management of orbital
      trapdoor fractures in children and to examine alterations in the morphology of
      the inferior rectus (IR) muscle. METHODOLOGY: Outcome assessment on patients
      undergoing surgery at the Hospital For Sick Children, Toronto with symptomatic
      orbital floor trapdoor fractures over a 10-year period and a CT-based
      morphometric analysis of the inferior rectus muscle were performed. RESULTS: 18
      patients (5F, 13M) mean age 12.6 years (range 8.3-16.6 years) underwent surgical
      exploration (average time to surgery 9.7 +/- 3.5 days (range 1-45 days). Follow
      up was 15.4 months (range 6-36 months). All patients noted improvement in extra
      ocular muscle (EOM) range of motion post-operatively: 7 patients had normal EOM
      with no diplopia; 9 patients had minimal diplopia on extreme secondary (upwards)
      gaze and 2 patients had residual significant diplopia with upward gaze. CT
      morphologic assessment (8 patients) demonstrated: a) zone of bony injury was
      posterior to the equator of the globe; b) minimal to no extra-conal fat exists to
      protect the IR muscle; c) a trend toward increased length in the injured IR
      muscle. CONCLUSIONS: With surgical intervention, improvement of diplopia
      (complete or near-complete resolution) occurred in 16/18 (89%) of patients
      presenting with symptomatic trapdoor orbital floor fractures. CT-based assessment
      demonstrated the vulnerability of the inferior rectus muscle with close proximity
      to the orbital floor and lack of periorbital fat for protection. Alteration of
      the length of the IR muscle may impact the force-length relationship and play a
      role in the outcomes. Early surgical intervention for symptomatic trapdoor
      fractures is recommended.

PMID- 22459796
TI  - Pharyngeal flap versus sphincter pharyngoplasty for the treatment of
      velopharyngeal insufficiency: a meta-analysis.
AB  - BACKGROUND: Velopharyngeal insufficiency (VPI) has been reported in 5-20% of
      patients following cleft palate repair. Since VPI can limit communication,
      determining which operative procedure leads to the greatest improvement is of
      utmost importance. Since there is no consensus, this meta-analysis aims to
      determine which procedure results in the most significant resolution of VPI.
      METHODS: Two independent assessors undertook a literature review for articles
      that compare procedures aimed at treating VPI. Study quality was determined using
      validated scales. Level of agreement was assessed using intra-class coalition
      coefficient analysis. The heterogeneity between studies was evaluated using I(2)
      and Cochran's Q-statistic. Random effect model analysis and forest plots were
      used to report a pooled odds ratio (OR) and 95% confidence intervals (CI) for
      treatment effect. A p-value of 0.05 was considered for statistical significance.
      RESULTS: Two randomised controlled trials (RCTs) comparing pharyngeal flap to
      sphincter pharyngoplasty were obtained. A total of 133 patients were included,
      with follow-ups at 3-4 months. The pooled OR was determined to be 2.95 (95% CI:
      0.66-13.23) in favour of the pharyngeal flap. CONCLUSIONS: Based on these RCTs,
      which currently compose the highest quality data that compares pharyngeal flap
      versus pharyngoplasty, the pooled treatment effect suggests a possible trend
      favouring pharyngeal flap.

PMID- 22459797
TI  - Pregnancy, keloids and capsules.

PMID- 22459799
TI  - Challenging narrow distal aorta in abdominal aortic aneurysm--endovascular repair
      using a reversed flared endoprosthesis.
AB  - INTRODUCTION: Narrow aortic bifurcations are a challenging issue while treating
      abdominal aortic aneurysm by endovascular means. Off-the-shelf products are often
      not suitable and special considerations and custom-made endoprostheses are
      necessary. REPORT: Alternatively, some morphologies qualify for a flared tube
      graft. We report two successful aneurysm exclusions using custom-made (Anaconda,
      Vascutek/Terumo) step-down diameter grafts in patients with tight distal aortas
      without the need for pre-interventional endograft adjustments. DISCUSSION: In
      these two cases, implantation of a custom-made proximally flared tube endograft
      in treating a localised abdominal aortic aneurysm with a narrow and calcified
      bifurcation seems feasible. They represent uncommon, yet challenging, issues
      worthy of attention.

PMID- 22459798
TI  - Dependence on tobacco and nicotine products: a case for product-specific
      assessment.
AB  - The International Classification of Diseases and the Diagnostic and Statistical
      Manual for diagnosing tobacco/nicotine dependence emphasize the dependence
      producing drug nicotine. These diagnostic tools have been challenged on grounds
      of poor predictive validity, and they do not differentiate across various forms
      of nicotine-containing products. In fact, nicotine-containing products (e.g.,
      tobacco cigarettes, smokeless tobacco [ST], waterpipe, electronic cigarettes
      [ECIGs], and nicotine replacement [NR] products) have very different
      characteristics both in terms of sensory and behavioral involvement and also in
      pharmacokinetic and pharmacodynamic effects. For example, a cigarette and a
      nicotine patch are very different on almost every one of these dimensions. When
      ability to stop using a nicotine/tobacco product is used as a criterion for
      dependence, success rates vary considerably across products: Tobacco cigarette
      cessation is more difficult than ST cessation that in turn is more difficult than
      NR product cessation. Based on these results, we hypothesize that there is a
      continuum of dependence as much as there is a continuum of harm, with tobacco
      cigarettes and NR products on opposite ends of both continua and other products
      (waterpipe and ECIGs) somewhere in between. In order to capture more precisely
      the dependence produced by both nicotine and its administration forms, product
      specific instruments may be required. The pros and cons of this approach are
      discussed.

PMID- 22459800
TI  - The protective effects of ozone therapy in a rat model of acetaminophen-induced
      liver injury.
AB  - OBJECTIVES: Acetaminophen (APAP) overdose may cause acute liver injury. Ozone
      therapy (OT) is shown to reduce inflammation and necrosis in several entities.
      Thus, we have designed this study to evaluate the efficacy of OT in a rat model
      of APAP-induced liver injury. METHODS: Twenty-seven Sprague-Dawley rats were
      divided into three groups: sham, APAP and APAP+OT groups. In the APAP and the
      APAP+OT groups, liver injury was induced by oral administration of 1 g/kg APAP.
      The APAP+OT group received a single dose ozone/oxygen mixture (0.7 mg/kg)
      intraperitoneally 1h after APAP administration. All animals were killed at 24
      hour after APAP administration. Blood samples and liver tissues were harvested to
      determine liver injury and oxidative stress parameters. Liver tissues and blood
      samples were obtained for biochemical and histopathological analyses. RESULTS:
      APAP administration caused necrosis in the liver after 24h. The degrees of liver
      necrosis of the APAP group were higher than the other groups (in both p<0.05,
      respectively). In the APAP+OT group, liver antioxidant enzymes activities were
      significantly higher than the APAP group (p<0.05), but were lower than the sham
      group (p<0.05). In the sham group, serum neopterin, a marker of cell-mediated
      immunity, concentrations (4.8+/-1.2 nmol/L) were lower than the APAP (14.7+/-1.4
      nmol/L) and APAP+OT groups (7.5+/-2.4 nmol/L) (in both p<0.05, respectively).
      CONCLUSION: Our results showed that OT prevented liver necrosis in rats and
      reduced neopterin levels. These findings suggest that the use of OT as an
      adjuvant therapy which might improve the outcome in APAP induced liver injury.

PMID- 22459801
TI  - Nuclear factor erythroid 2-like 2 (Nrf2) expression in end-stage liver disease.
AB  - The transcription factor Nrf2, encoded by NFE2L2 gene is a key regulator of
      cellular defense against oxidative and electrophilic stress, also governing the
      expression of many phase II detoxification enzymes. Nrf2 is negatively regulated
      by KEAP1 protein. Recent studies have shown that Nrf2 might also constitute an
      important mediator of inflammatory processes. In the current study the expression
      of Nrf2 in livers from patients with end-stage liver disease has been
      investigated. Surgical specimens were obtained from explanted livers of 24
      patients with end-stage liver disease of different etiology. Control samples were
      obtained from nontumoral liver tissue from 6 patients with metastatic liver
      tumors. Nrf2 expression was evaluated by means of qRT-PCR, Western-blot and
      immunohistochemical staining. KEAP1 gene expression was investigated at mRNA
      level. The expression of the NFE2L2 gene was decreased in all groups of end-stage
      liver disease samples as compared with the controls (mean 0.470+/-1.20 of the
      value observed in the control samples, p=0.003). Decreased values of NFE2L2/KEAP1
      mRNA ratio were also observed in end-stage liver disease groups (0.60+/-0.24 of
      the value observed in the control samples, p=0.019). The results were generally
      confirmed in Western-blot and immunohistochemical analysis of Nrf2 protein.
      Different expression pattern of Nrf2 regulated genes in end-stage liver disease
      samples were observed: glutamate-cysteine ligase (GCLC) and glutathione-S
      transferase A1 (GSTA1) were significantly down-regulated in most liver disease
      groups, whereas heme oxidase 1 (HMOX1) and NAD(P)H dehydrogenase [quinone] 1
      (NQO1) were not significantly suppressed. Treatment of HepG2 cells with pro
      inflammatory cytokines resulted in significant decrease of GSTA1, NFE2L2 and GCLC
      expression, while the exposure had no significant influence on KEAP1, HMOX1, and
      NQO1 mRNA levels. Nrf2 deficiency may be one of the factors underlying impaired
      liver function in detoxification processes. It remains to be established in
      further studies if the observed decrease of Nrf2 expression is just a result of
      liver cirrhosis or is primary, playing a role in disease pathogenesis.

PMID- 22459802
TI  - New high-performance liquid chromatography assay for glycosyltransferases based
      on derivatization with anthranilic acid and fluorescence detection.
AB  - Assays were developed using the unique labeling chemistry of 2-aminobenzoic acid
      (2AA; anthranilic acid, AA) for measuring activities of both beta1-4
      galactosyltransferase (GalT-1) and alpha2-6 sialyltransferase (ST-6) by high
      performance liquid chromatography (HPLC) with fluorescence detection (Anumula KR.
      2006. Advances in fluorescence derivatization methods for high-performance liquid
      chromatographic analysis of glycoprotein carbohydrates. Anal Biochem. 350:1-23).
      N-Acetylglucosamine (GlcNAc) and N-acetyllactosamine were used as acceptors and
      uridine diphosphate (UDP)-galactose and cytidine monophosphate (CMP)-N
      acetylneuraminic acid (NANA) as donors for GalT-1 and ST-6, respectively.
      Enzymatic products were labeled in situ with AA and were separated from the
      substrates on TSKgel Amide 80 column using normal-phase conditions. Enzyme units
      were determined from the peak areas by comparison with the concomitantly
      derivatized standards Gal-beta1-4GlcNAc and NANA-alpha2-6 Gal-beta1-4GlcNAc.
      Linearity (time and enzyme concentration), precision (intra- and interassay) and
      reproducibility for the assays were established. The assays were found to be
      useful in monitoring the enzyme activities during isolation and purification. The
      assays were highly sensitive and performed equal to or better than the
      traditional radioactive sugar-based measurements. The assay format can also be
      used for measuring the activity of other transferases, provided that the
      carbohydrate acceptors contain a reducing end for labeling. An assay for
      glycoprotein acceptors was developed using IgG. A short HPLC profiling method was
      developed for the separation of IgG glycans (biantennary G0, G1, G2, mono- and
      disialylated), which facilitated the determination of GalT-1 and ST-6 activities
      in a rapid manner. Furthermore, this profiling method should prove useful for
      monitoring the changes in IgG glycans in clinical settings.

PMID- 22459803
TI  - OcularTrauma Score: a useful predictor of visual outcome at six weeks in patients
      with traumatic cataract.
AB  - OBJECTIVE: To validate the predictive value of the Ocular Trauma Score (OTS) in
      injury cases with traumatic cataracts. DESIGN: Retrospective cohort study.
      PARTICIPANTS: A total of 787 eyes. METHODS: A total of 787 eyes of 787 subjects
      with traumatic cataracts were enrolled using specific inclusion criteria. The
      eyes were examined to review comorbidities caused by trauma. Surgery was
      performed for traumatic cataracts, lenses were implanted, and patients were
      treated for amblyopia, as applicable. The patients were reexamined 6 weeks
      postoperatively. On the basis of ocular trauma described according to the
      Birmingham Eye Trauma Terminology System, the patients were divided into 2
      traumatic cataract groups: open globe injury and closed globe injury. The
      relationship of visual acuity (VA) with demographic and clinical variables was
      analyzed. The visual outcomes were predicted using the OTS, and the predictions
      were compared with the actual outcomes using statistical tests. MAIN OUTCOME
      MEASURES: Visual acuity. RESULTS: At 6 weeks postoperatively, 245 eyes (31%) had
      a VA >= 20/40 and 480 eyes (61.0%) had a VA >20/200. The OTS prediction was not
      significantly different when compared with actual visual outcome at 6 weeks
      postoperatively in all OTS categories. CONCLUSIONS: The relationship of VA at 6
      weeks with demographic and clinical variables was analyzed. In this study, the
      OTS was found as a reliable tool to predict visual outcome in cases of traumatic
      cataracts 6 weeks postoperatively.

PMID- 22459804
TI  - [Mastocytosis and pregnancy].
AB  - Mastocytosis is a rare disorder characterized by an accumulation of mastocytes in
      cutaneous and visceral tissues. In the presence of stimuli such as stress, pain,
      drug administration and cutaneous compression, it can ultimately lead to
      cardiovascular collapse. In women with mastocytosis, pregnancy monitoring and
      pain management in the peripartum period can be challenging and should involve a
      multidisciplinary approach. In this article, we discuss our ante partum care and
      intra partum management, as illustrated by three recent cases.

PMID- 22459805
TI  - On parameter estimation in population models III: time-inhomogeneous processes
      and observation error.
AB  - Essential to applying a mathematical model to a real-world application is
      calibrating the model to data. Methods for calibrating population models often
      become computationally infeasible when the population size (more generally the
      size of the state space) becomes large, or other complexities such as time
      dependent transition rates, or sampling error, are present. Continuing previous
      work in this series on the use of diffusion approximations for efficient
      calibration of continuous-time Markov chains, I present efficient techniques for
      time-inhomogeneous chains and accounting for observation error. Observation error
      (partial observability) is accounted for by joint estimation using a scaled
      unscented Kalman filter for state-space models. The methodology will be
      illustrated with respect to models of disease dynamics incorporating seasonal
      transmission rate and in the presence of observation error, including application
      to two influenza outbreaks and measles in London in the pre-vaccination era.

PMID- 22459807
TI  - Effect of membrane length, membrane resistance, and filtration conditions on the
      fractionation of milk proteins by microfiltration.
AB  - We investigated the fractionation of casein micelles and the whey protein beta
      lactoglobulin (beta-LG) of skim milk by crossflow microfiltration (0.1 MUm) for
      the first time by a novel approach as a function of membrane length and membrane
      resistance. A special module was constructed with 4 sections and used to assess
      the effects of membrane length by measuring flux and beta-LG permeation (or
      transmission) as a function of transmembrane pressure and membrane length.
      Depending on the position, the membranes were partly controlled by a deposit
      layer. A maximum for beta-LG mass flow through the various membrane sections was
      found, depending on the position along the membrane. To study the effect of
      convective flow toward the membrane, membranes with 4 different intrinsic
      permeation resistances were assessed in terms of the permeation and fouling
      effects along the flow channel. From these findings, we derived a ratio between
      transmembrane pressure and membrane resistance, which was useful in reducing the
      effect of deposit formation and, thus, to optimize the protein permeation. In
      addition, the fouling effect was investigated in terms of reversible and
      irreversible fouling and, in addition, by differentiation between pressure
      induced fouling and adsorption-induced (pressure-independent) fouling, again as a
      function of membrane length.

PMID- 22459808
TI  - Effect of temperature and pH on the solubility of caseins: environmental
      influences on the dissociation of alpha(S)- and beta-casein.
AB  - Selective precipitation is a common method for the isolation of beta-casein,
      using the different calcium sensitivities of the individual caseins and the
      selective solubility of beta-casein at a low temperature. In previous studies, it
      has been indicated that the beta-casein yield depends on the physicochemical
      characteristics of the casein raw material used for fractionation. The objective
      of this study was to evaluate and compare the solubility of alpha(S)- and beta
      casein in solutions of micellar casein, sodium caseinate, and calcium caseinate
      as a function of pH and temperature. Additionally, the solubility of isolated
      alpha(S)- and beta-casein fractions in demineralized water, ultrafiltration
      permeate, and a calcium-depleted milk salt solution was investigated depending on
      the pH and temperature. Furthermore, micellar casein, sodium caseinate, and
      calcium caseinate were subjected to a calcium chloride-precipitation process to
      determine the solubility of alpha(S)- and beta-casein in calcium chloride
      precipitate, which is produced during selective precipitation, as a function of
      temperature and pH. Generally, the temperature had only a marginal influence on
      the alpha(S)-casein solubility compared with the beta-casein solubility, whereas
      the solubility was shown to be strongly influenced by the pH. Our results suggest
      that the yield of beta-casein obtained during isolation by means of selective
      precipitation may be a result of the solubility characteristics of alpha(S)- and
      beta-casein in calcium chloride precipitate. Manufacturers may consider a simple
      solubility experiment before the beta-casein isolation process by means of
      selective precipitation to predict beta-casein yield.

PMID- 22459809
TI  - Twelve-year cohort study on the influence of caprine arthritis-encephalitis virus
      infection on milk yield and composition.
AB  - This long-term observational cohort study was carried out to evaluate the effect
      of caprine arthritis-encephalitis virus (CAEV) infection on the quantitative and
      qualitative characteristics of milk production in dairy goats. For this purpose,
      a dairy herd comprising both CAEV-infected and uninfected female goats was
      observed for 12 consecutive years. Records on daily milk yield, somatic cell
      count (SCC), and contents of the major milk components (fat, protein and lactose)
      were collected every month. In total, 3,042 records (1,114 from CAEV-positive and
      1,928 from CAEV-negative animals) from 177 female goats were used for statistical
      analysis. The multi-trait repeatability test-day animal model using the
      derivative-free multivariate analysis package with the average information-REML
      method was applied to eliminate the influence of factors other than CAEV
      infection on milk production in goats. The statistical significance of the
      differences between estimates for seropositive and seronegative goats was
      evaluated using Student's t-test. The effect of age of goats (parity) on their
      serological status was also estimated with the one-trait repeatability test-day
      model. The serological status of goats was linked to parity: the higher the
      parity, the greater the probability of CAEV infection. No significant differences
      between infected and uninfected goats with respect to daily milk yield and SCC
      were found. On the other hand, the milk of uninfected goats contained more total
      protein (3.40% vs. 3.35%), fat (3.69% vs. 3.54%), and lactose (4.30% vs. 4.25%)
      than the milk of infected goats. Even though these differences were highly
      significant, they were small when expressed numerically.

PMID- 22459810
TI  - Heat stability of milk supplemented with calcium chloride.
AB  - Calcium chloride (0-25 mM) was added to skim milk powder that was reconstituted
      to 9% total solids. Heat stability was evaluated between 60 and 120 degrees C for
      different times by observing whether samples had coagulated, and by measuring the
      amount of sediment and residual protein in the centrifuged supernatant. Milk
      samples were also dialyzed during their respective heat treatments to recover the
      soluble phase at different temperatures to measure pH and ionic calcium. The
      transition conditions between good and poor heat stability were established for
      different calcium chloride concentrations and temperatures. As temperature
      increased, coagulation occurred at lower levels of added calcium chloride. The
      transition was quite distinct at higher temperatures but less so at lower
      temperatures; it was initiated by an increase in sediment formation before a firm
      coagulum was formed. Both pH and ionic calcium decreased in dialysates as
      temperature increased. No coagulation was observed if Ca(2+) was <0.5 mM and pH
      was >6.3 in dialysates taken at their respective coagulation temperatures. Being
      able to measure pH and ionic calcium at high temperatures will allow better
      understanding of factors affecting heat stability. Electrophoresis of the
      supernatants permitted identification of the protein fractions participating in
      the coagulation process. When coagulation was observed below 80 degrees C,
      substantial amounts of undenatured beta-lactoglobulin and alpha-lactalbumin were
      found in the supernatant, as well as some soluble casein fractions. All the major
      whey protein and casein fractions were found in the sediment.

PMID- 22459811
TI  - Estimation of Coxiella burnetii prevalence in dairy cattle in intensive systems
      by serological and molecular analyses of bulk-tank milk samples.
AB  - A large-scale investigation on Coxiella burnetii was carried out in dairy cattle
      herds from a Q fever-endemic region to evaluate the degree of exposure to C.
      burnetii and to estimate prevalences. This study included all of the dairy cattle
      herds from the province of Bizkaia, Northern Spain (n=178). Herds were visited
      between September 2009 and February 2010, and 100mL of bulk-tank milk (BTM) per
      farm was collected to be analyzed by ELISA and PCR. Blood samples were also taken
      from about 15 animals randomly selected from each herd. One hundred nineteen of
      the 178 studied herds (66.9+/-6.9%) were positive for the presence of anti-C.
      burnetii antibodies in BTM. Serum samples from 1,306 cows, 654 heifers, and 502
      calves were analyzed by ELISA, and cows showed a statistically significantly
      higher seroprevalence (12.3+/-1.8%) than heifers (1.1+/-0.8%) and calves (0.0+/
      0.0%). Eighty-nine herds (50.0+/-7.3%) had at least 1 seropositive animal, but
      within-herd prevalences higher than 20% were only observed in 24 herds (13.5+/
      5.0%). A significant correlation was observed between BTM ELISA sample-to
      positive control ratios and within-herd seroprevalence, being higher when
      considering only cows (R(2)=0.21). Animals from herds with negative BTM by ELISA
      showed a mean seroprevalence of 2.5%, whereas animals from herds with positive
      BTM samples had a statistically significantly higher seroprevalence (8.9%,
      F=19.7, degrees of freedom=1). The proportion of herds C. burnetii positive by
      BTM PCR was 51.7+/-7.3% (92/178). The widespread distribution of C. burnetii in
      cattle advocates for the implementation of Q fever control strategies.

PMID- 22459812
TI  - Characterization of coagulase-positive staphylococci isolated from tank and silo
      ewe milk.
AB  - The prevalence of coagulase-positive staphylococci (CPS) was studied among 390
      samples of ewe milk. Fifty-seven (14.85%) samples of tank milk and all samples
      (6) of silo milk gave a positive result on Baird-Parker agar base supplemented
      with rabbit plasma fibrinogen, whereas amplification of the coagulase (coa) gene
      was successful in 6 (1.56%) samples of tank milk and in all silo samples.
      Phenotypic and genetic analysis of 153 isolates identified 151 (98.69%) as
      Staphylococcus aureus. Amplification of the coa gene was positive for 149
      isolates (97.39%). The staphylococcal enterotoxin (SE) C gene was detected in 116
      strains (75.82%), whereas more than one SE gene was carried in 5 strains (3.26%).
      None of the isolates harbored the genes for SEE or for methicillin resistance. A
      high prevalence of CPS carrying enterotoxin genes should be of concern because
      ewe milk is mainly processed into raw milk cheeses. The detection of the coa gene
      from milk samples could help to assess the microbiological safety of raw milk
      intended for direct use in the dairy industry.

PMID- 22459813
TI  - Selection of potential probiotic lactobacilli for cholesterol-lowering properties
      and their effect on cholesterol metabolism in rats fed a high-lipid diet.
AB  - The objectives of this study were to screen probiotic characteristics of
      lactobacilli isolated from traditionally homemade koumiss products in Xinjiang
      and Inner Mongolia of China, and to determine and compare the effect of the
      Lactobacillus strains in vivo on lipid metabolism in rats fed with a high-lipid
      diet. Three out of 68 strains of Lactobacillus isolated from the koumiss were
      screened for bile-salt resistance, acid tolerance, and different
      hypocholesterolemic properties. The cholesterol-lowering effects of the 3
      screened strains were estimated in rats fed a high-lipid diet by determination of
      serum lipids, liver, and fecal cholesterol, fecal total bile acids, and short
      chain fatty acids. After a 4-wk feeding period, in comparison with the control
      group, the groups LIP-1 and MG9-2 had a significant reduction in serum total
      cholesterol, triglyceride and low-density lipoprotein cholesterol, and
      significantly increased high-density lipoprotein, the group E7301 had similar
      effects on serum lipids, but the change was not significant. The groups LIP-1,
      MG9-2 and E7301 had a significant reduction in liver cholesterol content and an
      increase in fecal cholesterol content compared with the control group. Total bile
      acid excretion was significantly higher in rats fed MG9-2 than the other groups.
      Rats fed diets containing lactic acid bacteria strains had significantly higher
      propionic acid and butyric acid concentrations in the feces compared with the
      control. Results indicated that the 3 screened Lactobacillus strains were able to
      lower cholesterol in vitro, and reduce cholesterol effectively in vivo. The
      mechanisms behind the hypocholesterolemic effect of 3 strains are likely to be
      diverse and will need further investigation.

PMID- 22459814
TI  - Proteolytic and proteomic changes in milk at quarter level following infusion
      with Escherichia coli lipopolysaccharide.
AB  - Mastitis is a major disease in dairy cattle, which causes significant economic
      losses due to decreased milk production, veterinary costs, and discarded milk.
      Escherichia coli is one of the most prevalent species of gram-negative bacteria
      that induce clinical mastitis. The objective of the present study was to
      characterize the proteolytic and proteomic changes in milk in response to
      infusion with lipopolysaccharide (LPS) at quarter level in a model mastitis
      system. One quarter of each of 2 cows was infused with 0.1 or 5 MUg of LPS. The
      somatic cell count of the infused quarters reached a peak 6 h after infusion to a
      greater extent in the cow infused with 5 MUg of LPS and changes in plasmin
      activity in milk differed between the 2 animals. Urea-polyacrylamide gel
      electrophoretograms of milk samples of the cow infused with 5 MUg of LPS obtained
      at different time points after infusion and incubated for up to 7 d showed almost
      full hydrolysis of beta- and alpha(s1)-casein during incubation of milk samples
      due to indigenous proteolytic activity. Two-dimensional gel electrophoretograms
      of milk at 0, 6, or 12 h after infusion with LPS showed hydrolysis of alpha(s)
      casein and beta-casein as well as the appearance of lower molecular weight
      products. Eleven fragments from proteolysis of the caseins were identified by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and,
      in addition, proteolysis patterns of casein by the indigenous bovine milk
      proteases plasmin and cathepsin D were studied in model studies using 2
      dimensional gel electrophoretograms. Twelve hours after infusion, lower abundance
      markers of inflammation were identified, including serotransferrin, fibrinogen
      beta chain, protein S100 A12, and the antimicrobial polypeptide cathelicidin.

PMID- 22459815
TI  - Functional properties of whey proteins microparticulated at low pH.
AB  - The main aim of the study was to assess the effect of microparticulation at low
      pH on the functionality of heat-denatured whey proteins (WP). Spray-dried,
      microparticulated WP (MWP) powders were produced from 7% (wt/wt) WP dispersions
      at pH 3, acidified with citric or lactic acid, and microfluidized with or without
      heat denaturation. Nonmicroparticulated, spray-dried powders produced at neutral
      pH or pH 3 served as controls. The powders were examined for their functional and
      physicochemical properties. Denatured MWP had an approximately 2 orders of
      magnitude reduction in particle size compared with those produced at neutral pH,
      with high colloidal stability indicated by substantially improved solubility. The
      detection of monomeric forms of WP in PAGE also confirmed the particle size
      reduction. Microparticulated WP exhibited enhanced heat stability, as indicated
      by thermograms, along with better emulsifying properties compared with those
      produced at neutral pH. However, MWP powders created weaker heat-induced gels at
      neutral pH compared with controls. However, they created comparatively strong
      cold acid-set gels. At low pH, a combination of heat and high hydrodynamic
      pressure produced WP micro-aggregates with improved colloidal stability that
      affects other functionalities.

PMID- 22459816
TI  - Optimal growth of Lactobacillus casei in a Cheddar cheese ripening model system
      requires exogenous fatty acids.
AB  - Flavor development in ripening Cheddar cheese depends on complex microbial and
      biochemical processes that are difficult to study in natural cheese. Thus, our
      group has developed Cheddar cheese extract (CCE) as a model system to study these
      processes. In previous work, we found that CCE supported growth of Lactobacillus
      casei, one of the most prominent nonstarter lactic acid bacteria (NSLAB) species
      found in ripening Cheddar cheese, to a final cell density of 10(8) cfu/mL at 37
      degrees C. However, when similar growth experiments were performed at 8 degrees C
      in CCE derived from 4-mo-old cheese (4mCCE), the final cell densities obtained
      were only about 10(6) cfu/mL, which is at the lower end of the range of the NSLAB
      population expected in ripening Cheddar cheese. Here, we report that addition of
      Tween 80 to CCE resulted in a significant increase in the final cell density of
      L. casei during growth at 8 degrees C and produced concomitant changes in
      cytoplasmic membrane fatty acid (CMFA) composition. Although the effect was not
      as dramatic, addition of milk fat or a monoacylglycerol (MAG) mixture based on
      the MAG profile of milk fat to 4mCCE also led to an increased final cell density
      of L. casei in CCE at 8 degrees C and changes in CMFA composition. These
      observations suggest that optimal growth of L. casei in CCE at low temperature
      requires supplementation with a source of fatty acids (FA). We hypothesize that
      L. casei incorporates environmental FA into its CMFA, thereby reducing its energy
      requirement for growth. The exogenous FA may then be modified or supplemented
      with FA from de novo synthesis to arrive at a CMFA composition that yields the
      functionality (i.e., viscosity) required for growth in specific conditions.
      Additional studies utilizing the CCE model to investigate microbial contributions
      to cheese ripening should be conducted in CCE supplemented with 1% milk fat.

PMID- 22459817
TI  - Consumer perception and sensory effect of oxidation in savory-flavored yogurt
      enriched with n-3 lipids.
AB  - The objective of this study was to determine the effects of different oils
      (butter, fish, and oxidized fish) on sensory characteristics of a savory [chile
      lime (CL)] low-fat yogurt using descriptive (unstructured line scales, 5
      attributes) and affective (hedonic) sensory testing methods. Yogurts were each
      manufactured at low [1.1-1.2% total fat; 0.43% added oil (wt/wt)] or high [1.6%
      total fat; 1% added oil (wt/wt)] levels of fish oil, with high levels of fish oil
      targeted to deliver 145 mg of docosahexaenoic acid+eicosapentaenoic acid/170 g of
      yogurt. In a preliminary study, untrained panelists (n=31), using triangle tests,
      did not discriminate between low levels of fish and butter oils in unflavored
      yogurts but could discern yogurt with oxidized fish oil, even at the low level.
      Trained panelists (n=12) described lower lime and acid flavor characteristics in
      CL-flavored yogurts containing 1% oxidized fish oil compared with yogurts
      containing low levels of oxidized fish oil and low or high levels of butter and
      fish oils. Oxidized flavor was higher in CL-flavored yogurts with oxidized fish
      oil (low and high) and with the high level of fish oil. Consumer ratings (n=100;
      9-point hedonic scale; 9="like extremely) of overall acceptability and flavor
      acceptability were bimodally distributed, with overall means between 4 and 5
      ("neither like nor dislike") for CL-flavored yogurt with butter or fish oils
      (high level). The upper 50% of responses for yogurt with butter or fish oil were
      6.51 and 6.31, respectively, for overall acceptability ("like slightly"), and
      7.02 and 6.56, respectively, for flavor acceptability. A large segment of
      consumers may be interested in incorporating heart-healthy n-3 lipids in their
      diets through frequent consumption of a savory yogurt enriched with n-3 fatty
      acids.

PMID- 22459818
TI  - Comparison of estrone and 17beta-estradiol levels in commercial goat and cow
      milk.
AB  - Increased levels of estrogen metabolites are believed to be associated with
      cancers of the reproductive system. One potential dietary source of these
      metabolites that is commonly consumed worldwide is milk. In North America, dairy
      cows are the most common source of milk; however, goats are the primary source of
      milk worldwide. In this study, the absolute concentrations of unconjugated and
      total (unconjugated plus conjugated) estrone (E(1)) and 17beta-estradiol (E(2))
      were compared in a variety of commercial cow milks (regular and organic) and goat
      milk. A lower combined concentration of E(1) and E(2) was found in goat milk than
      in any of the cow milk products tested. The differences in E(1) and E(2) levels
      between regular and organic cow milks were not as significant as the differences
      between goat milk and any of the cow milk products. Goat milk represents a better
      dietary choice for individuals concerned with limiting their estrogen intake.

PMID- 22459819
TI  - Short communication: Factors affecting coagulation properties of Mediterranean
      buffalo milk.
AB  - The aim of this study was to investigate sources of variation of milk coagulation
      properties (MCP) of buffalo cows. Individual milk samples were collected from 200
      animals in 5 herds located in northern Italy from January to March 2010. Rennet
      coagulation time (RCT, min) and curd firmness after 30 min from rennet addition
      (a(30), mm) were measured using the Formagraph instrument (Foss Electric,
      Hillerod, Denmark). In addition to MCP, information on milk yield, fat, protein,
      and casein contents, pH, and somatic cell count (SCC) was available. Sources of
      variation of RCT and a(30) were investigated using a linear model that included
      fixed effects of herd, days in milk (DIM), parity, fat content, casein content
      (only for a(30)), and pH. The coefficient of determination was 51% for RCT and
      48% for a(30). The most important sources of variation of MCP were the herd and
      pH effects, followed by DIM and fat content for RCT, and casein content for
      a(30). The relevance of acidity in explaining the variation of both RCT and
      a(30), and of casein content in explaining that of a(30), confirmed previous
      studies on dairy cows. Although future research is needed to investigate the
      effect of these sources of variation on cheese yield, findings from the present
      study suggest that casein content and acidity may be used as indicator traits to
      improve technological properties of buffalo milk.

PMID- 22459820
TI  - Mechanical properties of the bovine claw horn during lactation.
AB  - Claw horn disorders are one of the main causes of lameness in dairy cows
      globally. This study aimed to develop material testing techniques to assess
      changes in the mechanical properties of bovine claw horn (BCH) and to compare
      these mechanical properties with existing methods of assessing claw horn
      disorders during lactation. Lameness was also measured through locomotion scoring
      to assess the clinical significance of changes observed in the scoring for
      lesions. Experiment 1 used 8 claws collected from four 12 to 18 mo old beef
      heifers, to develop BCH sample storage methods and techniques to test the
      mechanical properties of BCH (puncture resistance and elastic modulus). The
      increase in the moisture content of BCH had a significant negative exponential
      effect on the elastic modulus of the sole and white line claw horn and a linear
      reduction in the puncture resistance of BCH. Placing BCH samples in sealed
      plastic bags and storing them either at 2 degrees C or by freezing samples at -22
      degrees C did not alter the dry matter content and, consequently, the mechanical
      properties of the claw horn tissue. In experiment 2, BCH was collected from 36
      lactating dairy cows and mechanical properties were tested using puncture
      resistance. Puncture resistance of the sole area of the claw horn decreased
      significantly when hemorrhages in the tested area increased. The puncture
      resistance of the sole and white line areas decreased at d 160 postpartum when
      the cows exhibited higher lesion scores and was lower in hind claws that had
      higher lesion scores when compared with the fore claws. The highest puncture
      resistance was found at 270 d postpartum, when the animals were at pasture.
      Puncture resistance was found to be an effective technique for assessing the
      effect of period of lactation and increasing hemorrhage levels on the mechanical
      properties and structural strength of bovine claw horn. It was found to be a good
      method of comparing changes and differences in mechanical properties and
      structural strength of BCH from the sole and white line areas within each claw
      and differences between claws. White line BCH consistently had significantly
      lower puncture resistance compared with the sole. Bovine claw horn with greater
      levels of hemorrhage or lower puncture resistance, or both, may provide less
      protection and increase the risk of foreign body penetration, trauma, and
      secondary infection of the corium of the claw.

PMID- 22459821
TI  - Endocrine milieu and developmental dynamics of ovarian cysts and persistent
      follicles in postpartum dairy cows.
AB  - Ovarian follicular cysts and persistent follicles are follicular pathologies
      involved in reduced fertility of dairy cows. Two separate experiments were
      performed on high-yielding Holstein cows to characterize ovarian cyclicity and
      evaluate the developmental dynamics of follicle pathologies postpartum. In
      experiment 1, 58 cows were monitored by ultrasonography twice weekly from d 18+/
      1 to 69+/-2 postpartum. First ovulation occurred 38+/-3, 27+/-2, 20+/-1, and 25+/
      3 d postpartum in cows with 1 cycle (n=11), 2 cycles (n=21), 3 cycles (n=13), and
      4 cycles (n=7), respectively. Follicular pathologies were developed in cows that
      were either acyclic (n=6) or had 1 or 2 cycles, but not in cows with more than 2
      cycles. In experiment 2, 47 cows were monitored twice weekly from 10 d postpartum
      to second ovulation. Follicles >=17 mm in diameter in 2 consecutive scans were
      aspirated, and concentrations of various hormones were measured. Cows were
      defined as cyclic (n=30; 64%) or with the potential to develop follicular
      pathology (n=17; 36%). Aspirated follicles (n=27) were classified into 3 main
      groups based on follicular growth rate, follicular diameter, and ovarian activity
      before and after follicular aspiration. Dominant follicles (n=4) were defined as
      large follicles (20 mm in diameter) with growth rate <=1 mm/d and normal ovarian
      activity. Persistent follicles (n=6) had the same growth rate and diameter as the
      dominant follicles, but persisted at the same diameter for >=10 d. Ovarian cysts
      (n=17) were defined as the largest follicular structures (19 to 32 mm in
      diameter), with abnormal growth rate (>1 mm/d) and abnormal ovarian activity.
      Single or turnover cysts did not differ in their growth parameters and were
      therefore combined and further classified according to follicular-fluid hormone
      concentrations. Estradiol-dominant cysts (n=7) were characterized by normal
      estradiol (284 to 659 ng/mL) and progesterone (20 to 113 ng/mL) concentrations,
      similar to those of the dominant follicle (554 to 993 ng/mL and 44 to 106 ng/mL,
      respectively). Progesterone-dominant cysts (n=5) were characterized by low
      estradiol (0.06 to 330 ng/mL) and high progesterone (586 to 3,288 ng/mL)
      concentrations. Low-steroidogenic active cysts (n=5) were characterized by low
      concentrations of both estradiol (23 to 61 ng/mL) and progesterone (17 to 205
      ng/mL). Characterization of spontaneously forming cysts might enable definition
      of the formation of ovarian follicular pathologies in postpartum cows.

PMID- 22459822
TI  - Automatic measurement of touch and release angles of the fetlock joint for
      lameness detection in dairy cattle using vision techniques.
AB  - This paper describes a synchronized measurement system combining image and
      pressure data to automatically record the angle of the metacarpus and metatarsus
      bones of the cow with respect to a vertical line, which is useful for lameness
      detection in dairy cattle. A camera system was developed to record the posture
      and movement of the cow and the timing and position of hoof placement and release
      were recorded using a pressure sensitive mat. Experiments with the automatic
      system were performed continuously on a farm in Ghent (Belgium) for 5 wk in
      September and October 2009. In total, 2,219 measurements were performed on 75
      individual lactating Holstein cows. As a reference for the analysis of the
      calculated variables, the locomotion of the cows was visually scored from
      recorded videos by a trained observer into 3 classes of lameness [53.5% were
      scored with gait score (GS)1, 33.3% were scored with GS2, and 9.3% were scored
      with GS3]. The contact data of the pressure mat and the camera images recorded by
      the system were synchronized and combined to measure different angles of the legs
      of the cows, together with the range of motion of the leg. Significant
      differences were found between the different gait scores in the release angles of
      the front hooves, in the range of motion of the front hooves, and in the touch
      angles of the hind hooves. The contact data of the pressure mat and the camera
      images recorded by the system were synchronized and combined to measure different
      angles of the legs of the cows, together with the range of motion of the leg.
      With respect to the classification of lameness, the range of motion of the front
      hooves (42.1 and 42.8%) and the release angle of the front hooves (41.7 and
      42.0%) were important variables. In 83.3% of the cows, a change in GS led to an
      increase in within-cow variance for the range of motion or the release angle of
      the front hooves. In 76.2% of the cows, an increase in GS led to a decrease in
      range of motion or an increase in release angle of the front hooves.

PMID- 22459823
TI  - Blood immunometabolic indices and polymorphonuclear neutrophil function in
      peripartum dairy cows are altered by level of dietary energy prepartum.
AB  - Cows experience some degree of negative energy balance and immunosuppression
      around parturition, making them vulnerable to metabolic and infectious diseases.
      The effect of prepartum feeding of diets to meet (control, 1.34 Mcal/kg of dry
      matter) or exceed (overfed, 1.62 Mcal/kg of dry matter) dietary energy
      requirements was evaluated during the entire dry period (~45 d) on blood
      polymorphonuclear neutrophil function, blood metabolic and inflammatory indices,
      and milk production in Holstein cows. By design, dry matter intake in the overfed
      group (n=9) exceeded energy requirements during the prepartum period (-4 to -1 wk
      relative to parturition), resulting in greater energy balance when compared with
      the control group (n=10). Overfed cows were in more negative energy balance
      during wk 1 after calving than controls. No differences were observed in dry
      matter intake, milk yield, and milk composition between diets. Although
      nonesterified fatty acid concentration pre- (0.138 mEq/L) and postpartum (0.421
      mEq/L) was not different between diets, blood insulin concentration was greater
      in overfed cows prepartum (16.7 MUIU/mL) compared with controls pre- and
      postpartum (~3.25 MUIU/mL). Among metabolic indicators, concentrations of urea
      (4.63 vs. 6.38 mmol/L), creatinine (100 vs. 118 MUmol/L), and triacylglycerol
      (4.0 vs. 8.57 mg/dL) in overfed cows were lower prepartum than controls. Glucose
      was greater pre- (4.24 vs. 4.00 mmol/L) and postpartum (3.49 vs. 3.30 mmol/L)
      compared with control cows. Among liver function indicators, the concentration of
      bilirubin increased by 2 to 6 fold postpartum in control and overfed cows.
      Phagocytosis capacity of polymorphonuclear neutrophils was lower prepartum in
      overfed cows (32.7% vs. 46.5%); phagocytosis in the control group remained
      constant postpartum (50%) but it increased at d 7 in the overfed group to levels
      similar to controls (48.4%). Regardless of prepartum diet, parturition was
      characterized by an increase in nonesterified fatty acid and liver
      triacylglycerol, as well as blood indices of inflammation (ceruloplasmin and
      haptoglobin), oxidative stress (reactive oxygen metabolites), and liver injury
      (glutamic oxaloacetic transaminase). Concentrations of the antioxidant and anti
      inflammatory compounds vitamin A, vitamin E, and beta-carotene decreased after
      calving. For vitamin A, the decrease was observed in overfed cows (47.3 vs. 27.5
      MUg/100 mL). Overall, overfeeding energy and higher energy status prepartum led
      to the surge of insulin and had a transient effect on metabolism postpartum.

PMID- 22459824
TI  - Alterations of fatty acid beta-oxidation capability in the liver of ketotic cows.
AB  - Dairy cows are highly susceptible to ketosis after parturition. In the present
      study, we evaluated the expression of fatty acid beta-oxidation-related enzymes
      in the liver of ketotic (n=6) and nonketotic (n=6) cows. Serum levels of
      nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), and glucose were
      determined by using standard biochemical techniques. The mRNA abundance and
      protein content of acyl-CoA synthetase long-chain (ACSL), carnitine
      palmitoyltransferase I (CPT I), carnitine palmitoyltransferase II (CPT II), acyl
      CoA dehydrogenase long chain (ACADL), 3-hydroxy-3-methylglutaryl-CoA synthase
      (HMGCS), and acetyl-CoA carboxylase (ACC) were evaluated by real-time PCR and
      ELISA. We found that serum glucose levels were lower in ketotic cows than in
      nonketotic cows, but serum BHBA and NEFA concentrations were higher. Messenger
      RNA and protein levels of ACSL were significantly higher in livers of ketotic
      cows than those in nonketotic cows. In contrast, mRNA levels of CPT I and mRNA
      and protein levels of CPT II, ACADL, HMGCS, and ACC were decreased in the liver
      of ketotic cows. Serum NEFA concentration positively correlated with ACSL protein
      levels and negatively correlated with protein levels of CPT II, HMGCS, ACADL, and
      ACC. In addition, serum BHBA concentration negatively correlated with protein
      levels of CPT II, HMGCS, and ACADL. Overall, fatty acid beta-oxidation capability
      was altered in the liver of ketotic compared with nonketotic cows. Furthermore,
      high serum NEFA and BHBA concentrations play key roles in affecting pathways of
      fatty acid metabolism in the liver.

PMID- 22459825
TI  - Association of plasma insulin concentration to fatty acid distribution between
      milk fat and membrane synthesis.
AB  - We examined the association between plasma insulin concentration and fatty acid
      distribution to milk fat and membrane fractions (triglyceride and phospholipid,
      respectively) in dairy cows. Thirty-seven Holstein cows at 60 to 70 d postpartum
      were synchronized by 2 PGF(2alpha) injections 14 d apart. Plasma samples were
      taken before morning and evening milkings and milk samples were obtained at
      morning milking. Plasma insulin concentrations were determined and cows were
      retrospectively assigned to low insulin (LI; 2.8+/-0.2 ng/mL, n=6) or high
      insulin (HI; 5.9+/-0.6 ng/mL, n=7) experimental groups. Fatty acid analysis of
      milk samples demonstrated a possible association between plasma insulin
      concentration and the fatty acid composition in phospholipid and triglyceride
      fractions. In the HI group, monounsaturated fatty acid concentration tended to be
      higher in the triglyceride (Tg) fraction than the phospholipids (Pl) fraction. In
      the LI group, the concentrations of short- and medium-chain saturated fatty acids
      (<16 carbon chain length), considered de novo-synthesized fatty acids, were
      higher in the triglyceride fraction than the phospholipid fraction. These results
      imply that the primary source of saturated fatty acids for phospholipid
      synthesis, in both HI and LI groups, is the circulation, as reflected by a higher
      concentration of longer saturated fatty acids (>16 carbon chain length) in the
      phospholipid fraction. Finally, the phospholipid-to-triglyceride ratio was higher
      in the HI group than in the LI group. Together, the results indicate that fatty
      acid distribution between phospholipid (membrane) and triglyceride (fat)
      synthesis by the mammary gland is associated with fatty acid length, degree of
      unsaturation, and origin, and might be subject to metabolic hormone regulation.
      Furthermore, a lower triglyceride-to-phospholipid ratio in the HI group implies
      that high plasma insulin and low milk fat concentrations are associated with a
      shift in the size distribution of milk fat globules.

PMID- 22459826
TI  - Effect of endocervical inflammation on days to conception in dairy cows.
AB  - In contrast to endometritis, now diagnosed by cytological examination, the effect
      of endocervical inflammation on reproductive performance has been inadequately
      investigated. In this study, endocervical and endometrial cytological specimens
      were collected from 168 Holstein cows between 21 and 60 days in milk (DIM) to
      investigate the prevalence of endocervical inflammation and effect on days to
      conception. Statistical analyses were stratified based on DIM at examination (<35
      vs. >=35 DIM). Endocervical inflammation with >=5% neutrophils before 35 DIM
      (disregarding the level of endometrial inflammation) was associated with
      decreased hazard of pregnancy within 300 DIM (adjusted hazard ratio, 0.4; 95%
      confidence interval: 0.3-0.8). A decrease in hazard of pregnancy was observed
      when >6% neutrophils were counted in endometrial smears (adjusted hazard ratio,
      0.4; 95% confidence interval: 0.2-0.7). The study suggested an additive effect of
      combined endocervical and endometrial inflammation on the hazard of pregnancy
      within 300 DIM. Using the thresholds of 5% neutrophils for the cervix and 6%
      neutrophils for the uterus, 11% of the cows examined before 35 DIM presented
      cervicitis only, 13% were affected by endometritis only, and 32% suffered from
      both endometrial and endocervical inflammation. The presence (absence) of
      cervicitis was not indicative of the presence (absence) of endometritis. This
      study showed that in addition to uterine inflammation, endocervical inflammation
      in early lactation affects conception. Thus, the global evaluation of genital
      tract health may be more beneficial for reproductive performance than that of
      endometrial inflammation.

PMID- 22459827
TI  - On-farm estimation of energy balance in dairy cows using only frequent body
      weight measurements and body condition score.
AB  - Precise energy balance estimates for individual cows are of great importance to
      monitor health, reproduction, and feed management. Energy balance is usually
      calculated as energy input minus output (EB(inout)), requiring measurements of
      feed intake and energy output sources (milk, maintenance, activity, growth, and
      pregnancy). Except for milk yield, direct measurements of the other sources are
      difficult to obtain in practice, and estimates contain considerable error
      sources, limiting on-farm use. Alternatively, energy balance can be estimated
      from body reserve changes (EB(body)) using body weight (BW) and body condition
      score (BCS). Automated weighing systems exist and new technology performing semi
      automated body condition scoring has emerged, so frequent automated BW and BCS
      measurements are feasible. We present a method to derive individual EB(body)
      estimates from frequently measured BW and BCS and evaluate the performance of the
      estimated EB(body) against the traditional EB(inout) method. From 76 Danish
      Holstein and Jersey cows, parity 1 or 2+, on a glycerol-rich or a whole grain
      rich total mixed ration, BW was measured automatically at each milking. The BW
      was corrected for the weight of milk produced and for gutfill. Changes in BW and
      BCS were used to calculate changes in body protein, body lipid, and EB(body)
      during the first 150 d in milk. The EB(body) was compared with the traditional
      EB(inout) by isolating the term within EB(inout) associated with most
      uncertainty; that is, feed energy content (FEC);
      FEC=(EB(body)+EMilk+EMaintenance+Eactivity)/dry matter intake, where the energy
      requirements are for milk produced (EMilk), maintenance (EMaintenance), and
      activity (EActivity). Estimated FEC agreed well with FEC values derived from
      tables (the mean estimate was 0.21 MJ of effective energy/kg of dry matter or
      2.2% higher than the mean table value). Further, the FEC profile did not suggest
      systematic bias in EB(body) with stage of lactation. The EB(body) estimated from
      daily BW, adjusted for milk and meal-related gutfill and combined with frequent
      BCS, can provide a successful tool. This offers a pragmatic solution to on-farm
      calculation of energy balance with the perspective of improved precision under
      commercial conditions.

PMID- 22459828
TI  - Low progesterone concentration during the development of the first follicular
      wave reduces pregnancy per insemination of lactating dairy cows.
AB  - Objectives were to determine the effect of progesterone (P4) concentration on
      fertility of lactating dairy cows induced to ovulate follicles of the first
      follicular wave. Lactating dairy cows (n=989) at 38+/-3d postpartum were balanced
      by parity and body condition score and randomly assigned to 3 treatments: first
      follicular wave (FFW), first follicular wave with exogenous P4 (FFWP), or second
      follicular wave (SFW). All cows had their estrous cycle presynchronized with 2
      injections of prostaglandin (PG) F(2alpha) given 14 d apart. Cows in the FFW and
      FFWP treatments started the ovulation synchronization protocol 3 d after the last
      PGF(2alpha) of the presynchronization protocol, whereas SFW cows received a GnRH
      injection (100 MUg of gonadorelin diacetate; Cystorelin, Merial Ltd., Duluth, GA)
      3 d after the last PGF(2alpha) of the presynchronization protocol and started the
      synchronization protocol 7 d later. The synchronization protocol consisted of
      GnRH on d -10, PGF(2alpha) on d -3, and GnRH concurrent with timed artificial
      insemination (AI) on d 0. Cows in the FFWP treatment received 2 controlled
      internal drug release inserts containing 1.38 g of P4 from d -8 to -3.
      Progesterone concentration was determined on d -10, -8, -6, -3, and 0 from all
      cows and at 7, 14, and 21 d after AI from a subsample of cows (n=170). Cows
      (n=715) had their ovaries scanned by ultrasound on d -10, -3, and 7 d. Pregnancy
      was diagnosed at 38 and 66 d after AI. Concentration of P4 from study d -8 to -3
      was lowest for FFW cows (1.4+/-0.1 ng/mL) and similar between SFW (3.7+/-0.2
      ng/mL) and FFWP (3.7+/-0.1 ng/mL) cows. Diameter of the dominant follicle on
      study d -3 was greater for FFW cows (16.5+/-0.3 mm) than for SFW cows (15.4+/-0.3
      mm), but diameter of the dominant follicle of FFWP cows was not different (15.9+/
      0.3 mm) compared with that of SFW and FFW cows. The incidence of multiple
      ovulation was largest for FFW cows (SFW=19.5, FFW=33.6, FFWP=19.0%), but
      pregnancy per AI (P/AI) at 66 d was smallest for FFW cows (SFW=38.9, FFW=22.3,
      FFWP=32.0%). Anovular cows in the SFW (19.4 vs. 42.8%) and FFWP (22.1 vs. 37.2%)
      treatments had reduced P/AI compared with cyclic cows, despite having similar or
      greater P4 concentration from study d -8 to -3, respectively. Estrus and
      ovulation synchronization protocols for lactating dairy cows must result in
      growth of ovulatory follicle under P4 concentration >2 ng/mL to ensure high P/AI.

PMID- 22459829
TI  - Role of metabolic and cellular proliferation genes in ruminal development in
      response to enhanced plane of nutrition in neonatal Holstein calves.
AB  - We evaluated expression of 50 genes encoding enzymes involved in metabolism,
      cellular growth, and various transporters in ruminal epithelium tissue when
      calves were fed conventional milk replacer (MR) and starter (control) or enhanced
      MR and enhanced starter. Male Holstein calves were fed reconstituted control MR
      [20% crude protein (CP), 20% fat; 0.57 kg of solids/calf] plus conventional
      starter (19.6% CP, dry matter basis) or a high-protein MR (ENH; 28.5% CP, 15%
      fat; at ~2% of body weight) plus high-CP starter (25.5% CP, dry matter basis).
      Groups of calves in control and ENH were harvested after 43 d (wk 5) and 71 d (wk
      10) of feeding. Ruminal epithelium from 5 calves (3 to 42 d age) in each group
      was used for transcript profiling using quantitative reverse transcription PCR.
      No differences were observed for plasma beta-hydroxybutyrate (BHBA) concentration
      but BHBA increased by wk 10 regardless of treatment. Reticulorumen mass
      postweaning was greater in calves consuming the ENH diet and corresponded with
      overall greater serum insulin. A marked upregulation of the ketogenic genes
      HMGCS2, HMGCL, and BDH1 was observed, concomitant with downregulation of
      expression of genes involved in fatty acid oxidation (CPT1A, ACADVL) at wk 10.
      Higher relative percentage mRNA abundance of HMGCS2 (~40% of total genes
      assayed), the rate-controlling enzyme in hepatic ketogenesis, underscored its
      importance for ruminal cell energy metabolism. Higher PPARA expression and blood
      nonesterified fatty acids at wk 5 due to ENH were suggestive of more extensive
      long-chain fatty acid oxidation in ruminal epithelial cells during the milk-fed
      phase. In contrast, calves fed control consumed more starter during the milk-fed
      phase, which likely increased production of volatile fatty acids and accounted
      for higher expression of propionyl-CoA carboxylase (PCCA) and the Na(+)/H(+)
      exchanger 2 (SLC9A2) at wk 5. Expression of G-coupled protein receptors for short
      chain fatty acids was undetectable. The expression of the urea transporter
      (SLC14A1) increased markedly with age and was correlated with the increase in
      blood urea N. Expression of genes involved in cell proliferation (INSR, FOXO1,
      AKT3) was greater for ENH primarily during the milk-fed period and corresponded
      with greater serum insulin. The greater reticuloruminal mass in calves fed ENH
      postweaning underscores the importance of feeding high-quality starter and
      indicates that fermentability of the diet, by providing metabolic fuel for
      ruminal epithelial cells, is a primary driver of ruminal development postweaning.
      From a mechanistic standpoint, the 7-fold increase in expression of the nuclear
      receptor PPARD (~40-fold more abundant than PPARA) suggests a key role in
      controlling biological processes driving ruminal epithelial cell development.
      Elucidating ligands of PPARD may provide the means for nutritional regulation of
      rumen development.

PMID- 22459830
TI  - An experimental infection model to induce digital dermatitis infection in cattle.
AB  - Bovine digital dermatitis (DD), also known as papillomatous digital dermatitis
      (foot warts), has been recognized as a major cause of lameness in cattle, with
      important economic and welfare consequences. The evaluation of therapeutic and
      preventive interventions aiming to control DD infections in dairy cattle is often
      challenged by the complex multifactorial etiology of the disease. An experimental
      infection model to induce acute DD lesions in a controlled environment is
      proposed. The goal was to provide a standard way of reproducing DD infections
      independent of external factors that could confound the natural course of the
      disease, such as management practices or infection pressure, resulting in
      transmission of DD between animals. A group of 4 yearling Holstein heifers free
      of any clinical evidence of hoof disease was recruited from a commercial dairy
      farm and housed in an experimental facility in 1 pen with slatted flooring. The
      hind feet were wrapped to mimic conditions of prolonged moisture (maceration) and
      reduced access to air (closure) and inoculated at the heel and dewclaw areas with
      a homogenate of a naturally occurring DD lesion skin biopsy or a culture broth of
      Treponema spp. After a period of 12 to 25 d, 4 of 6 and 1 of 4 dewclaw areas
      inoculated with biopsied DD lesion or a Treponema spp. culture, respectively, had
      gross lesions compatible with DD. Histopathology confirmed the gross diagnosis in
      the sites inoculated with tissue homogenate. In the site inoculated with
      Treponema spp. culture broth, histopathology revealed an incipient DD lesion.
      Treponema spp. were detected by PCR in both naturally occurring DD homogenate and
      Treponema spp. culture broth inoculation sites. An experimental infection model
      to induce acute DD in cattle was developed, which may be used to evaluate
      interventions to control DD and study the pathogenesis of this infectious hoof
      disease in a controlled manner.

PMID- 22459831
TI  - Prostaglandin F2alpha and gonadotropin-releasing hormone administration improve
      progesterone status, luteal number, and proportion of ovular and anovular dairy
      cows with corpora lutea before a timed artificial insemination program.
AB  - The objective of this research was to increase the proportion of cows with at
      least 1 functional corpus luteum (CL) and elevated progesterone at the onset of
      the timed artificial insemination (TAI) protocol. Postpartum Holstein cows in one
      herd were stratified by lactation number at calving (September 2009 through
      August 2010) and assigned randomly to 2 treatments: 1) Presynch-10 (n=105): two
      25-mg injections of PGF(2alpha) (PG) 14 d apart (Presynch); and 2) PG-3-G
      (n=105): one 25-mg injection of PG 3 d before 100-MUg GnRH (Pre-GnRH) injection,
      with the PG injection administered at the same time as the second PG injection in
      the Presynch-10 treatment. Cows were enrolled in a TAI protocol [Ovsynch;
      injection of GnRH 7 d before (GnRH-1) and 56 h after (GnRH-2) PG injection with
      AI 16 to 18 h after GnRH-2] 10 d after the second or only PG injection. Blood
      samples for progesterone or estradiol analyses were collected on median days in
      milk (DIM): 36, 39, 50, 53 (Pre-GnRH), 60 (GnRH-1), 67 (PG), 69 (GnRH-2), and 70
      (TAI). Ovarian structures were measured by ultrasonography on median DIM 53, 60,
      67, 69, and 6 d post-TAI to determine follicle diameters, ovulation response to
      GnRH, or both. Although progesterone concentration did not differ between
      treatments before Pre-GnRH injection, the proportion of cows with at least 1 CL
      tended to be greater for PG-3-G than Presynch-10 cows, and more PG-3-G cows
      ovulated after Pre-GnRH injection than ovulated spontaneously in Presynch-10.
      Further, the diameter of follicles that ovulated tended to be smaller in PG-3-G
      than in Presynch-10 cows after Pre-GnRH injection. At GnRH-1, the proportion of
      cows with progesterone >=1 ng/mL, the number of CL per cow, and the proportion of
      cows with at least 1 CL were greater for PG-3-G than Presynch-10. Neither
      follicle diameter nor percentage of cows ovulating after GnRH-1 differed between
      treatments. At PG injection during the week of TAI, progesterone concentration
      and the proportion of cows with progesterone >=1 ng/mL tended to be greater for
      PG-3-G than Presynch-10, and PG-3-G had more CL per cow than Presynch-10. No
      ovarian characteristics differed between treatments after GnRH-2, including
      progesterone concentration, number of CL per cow, and total luteal volume 7 d
      after GnRH-2. Many of the previous ovarian traits were improved in both ovular
      and anovular cows after PG-3-G compared with Presynch-10. Pregnancies per AI at d
      32 and 60 were only numerically greater for PG-3-G than for Presynch-10 cows,
      largely because of differences detected during months without heat stress. We
      concluded that the PG-3-G treatment increased ovulation rate and luteal function
      7 d before the onset of Ovsynch, resulting in improved follicular synchrony and
      predisposing potentially greater pregnancies per AI in lactating dairy cows.

PMID- 22459832
TI  - Risk factors and effects of postpartum anovulation in dairy cows.
AB  - The objectives were to identify risk factors for and to quantify the effect of
      postpartum anovulation on reproductive performance in dairy cows. Data from 2,178
      Holstein cows in 6 commercial herds enrolled in a randomized clinical trial were
      used. Data on periparturient disease incidence, calving history, and body
      condition score were collected. Cows were examined at wk 5 postpartum for
      reproductive tract disease; cytological endometritis was defined as >=6%
      polymorphonuclear cells in endometrial cytology, and purulent vaginal discharge
      was defined as the presence of mucopurulent or purulent vaginal discharge. Cows
      were followed until 300 d in milk (DIM) for reproductive performance. Serum
      nonesterified fatty acids (NEFA) concentration was measured once during the week
      before expected calving. Serum beta-hydroxybutyrate, NEFA, and haptoglobin were
      measured at wk 1, 2, and 3 postpartum. Serum progesterone (P4) was measured at wk
      3, 5, 7, and 9 postpartum. The end of the postpartum anovulation period was
      defined as the first sampling time at which P4 was >1 ng/mL. Statistical analyses
      were performed using logistic regression models and Cox proportional hazard
      models. The prevalence of anovulation was 72, 44, 26, and 17% at wk 3, 5, 7, and
      9, respectively. Cows were classified according to their ovulatory status as
      having luteal function at 21 DIM (Cyc21), as having low P4 at 21 DIM but having
      luteal function at least once at 35 or 49 or 63 DIM (Cyc63), or being anovulatory
      at 63 DIM (Anov63; no samples with P4 >1 ng/mL). Factors associated with early
      ovulation (Cyc21) included season, parity, decreased haptoglobinemia, and
      decreased serum NEFA concentration before and after parturition. Risk factors for
      prolonged anovulation (Anov63) included cytological endometritis, increased
      haptoglobinemia, and greater serum NEFA concentrations before and after
      parturition. Cows classified as Anov63 had an increased median time to first
      breeding compared with Cyc63 (74.1 vs. 73.2 d). The effect of prolonged
      postpartum anovulation on median time to pregnancy was conditional on parity
      group; a detrimental effect was present in cows of parity >=3 (129 d for Cyc21,
      151 d for Cyc63, and 180 d for Anov63), but no effect was observed in cows of
      parity <=2. Overall, these findings suggest that postpartum anovulation was
      associated with indicators of energy balance and uterine inflammation, and with
      detrimental effects on reproductive performance.

PMID- 22459833
TI  - Economic analysis of Mycobacterium avium subspecies paratuberculosis vaccines in
      dairy herds.
AB  - Johne's disease, or paratuberculosis, is a chronic infectious enteric disease of
      ruminants, caused by infection with Mycobacterium avium ssp. paratuberculosis
      (MAP). Given the absence of a fail-safe method of prevention or a cure, Johne's
      disease can inflict significant economic loss on the US dairy industry, with an
      estimated annual cost of over $200 million. Currently available MAP control
      strategies include management measures to improve hygiene, culling MAP serologic-
      or fecal-positive adult cows, and vaccination. Although the 2 first control
      strategies have been reported to be effective in reducing the incidence of MAP
      infection, the changes in herd management needed to conduct these control
      strategies require significant effort on the part of the dairy producer. On the
      other hand, vaccination is relatively simple to apply and requires minor changes
      in herd management. Despite these advantages, only 5% of US dairy operations use
      vaccination to control MAP. This low level of adoption of this technology is due
      to limited information on its cost-effectiveness and efficacy and some important
      inherent drawbacks associated with current MAP vaccines. This study investigates
      the epidemiological effect and economic values of MAP vaccines in various stages
      of development. We create scenarios for the potential epidemiological effects of
      MAP vaccines, and then estimate economically justifiable monetary values at which
      vaccines become economically beneficial to dairy producers such that a net
      present value (NPV) of a farm's net cash flow can be higher than the NPV of a
      farm using no control or alternative nonvaccine controls. Any vaccination with
      either low or high efficacy considered in this study yielded a higher NPV
      compared with a no MAP control. Moreover, high-efficacy vaccines generated an
      even higher NPV compared with alternative controls, making vaccination
      economically attractive. Two high-efficacy vaccines were particularly effective
      in MAP control and NPV maximization. One was a high-efficacy vaccine that reduced
      susceptibility to MAP infection. The other was a high-efficacy vaccine that had
      multiple efficacies on the dynamics of MAP infection and disease progress. Only
      one high-efficacy vaccine, in which the vaccine is targeted at reducing MAP
      shedding and the number of clinical cases, was not economically beneficial to
      dairy producers compared with an alternative nonvaccine control, when herds were
      highly infected with MAP.

PMID- 22459834
TI  - Risk factors for a high somatic cell count at the first milk recording in a large
      sample of UK dairy herds.
AB  - The dry period is important for the cure of existing intramammary infection (IMI)
      and the acquisition of new IMI. Somatic cell count (SCC) at both the last milk
      recording before drying off and at the first milk recording following calving can
      be used on farm to describe the dynamics of IMI during the dry period. The aims
      were to quantify the association between the main risk factors collected from
      milk recording data and the occurrence of a high SCC in early lactation as well
      as to partition the observed variation into the prevalence of high SCC in within
      herd and between-herd variation. Milk recording data collected between 2004 and
      2006 from 2,000 herds in England and Wales were used. Cows with an SCC >=200,000
      cells/mL were classified as high, and other cows as low. The median prevalences
      of the high classification were 42 and 21% at the last milk recording before
      drying off and the first milk recording following calving, respectively. Cows
      classified high or producing more milk before drying off as well as cows of
      greater parity or recorded in early lactation were more likely classified high at
      the first recording following calving. Cows from herds in which the prevalences
      of the high classification or the probability of remaining or becoming high over
      the dry period were elevated during the previous year were more likely classified
      as high at the first recording following calving. Half of the variability in the
      proportion of cows with a high SCC after calving originated at the herd level.
      The other half was unexplained within herd, but by between-year variability. Most
      cow-level predictors were important in explaining individual cow performance, but
      accounted for little of the overall between-herd variability. Of the predictors
      identified as important at the cow level, only milk yield at drying off was
      important in explaining the between-herd variability.

PMID- 22459835
TI  - Chronic mastitis is associated with altered ovarian follicle development in dairy
      cattle.
AB  - Connection between mastitis and fertility is multifaceted; therefore, several
      aspects need more elucidation. In particular, the aim was to investigate if
      naturally occurring chronic mastitis has an effect on ovarian function. At the
      time of slaughter, a milk sample and both ovaries were collected from 68 cows.
      The presence and intensity of chronic mastitis was diagnosed by the combined
      evaluation of bacteriological examination and somatic cell count of the milk of
      each individual quarter according to the measures of the National Mastitis
      Council. Animals were divided into 4 groups characterized by a low (n=15), mild
      (n=14), intense (n=19), or severe (n=16) degree of infection. A count of visible
      follicles on each ovary was followed by a quantitative analysis of microscopic
      traits on a selected group of animals (n=16). The latter included the
      classification and count of the entire preantral follicle population, and the
      morphometric analysis of the vascular bed extension and connective stroma in the
      cortical region. Finally, the expression of growth and differentiation factor-9
      (GDF-9) was studied. The number of follicles with diameters ranging from 1 to 3
      mm and 4 to 7 mm was not affected by the degree of infection. A significant
      effect of the degree of udder infection was observed on the number of follicles
      with a diameter larger than 8 mm. Furthermore, the intensity of mastitis had no
      effect on the number of primordial and primary follicles, but severely affected
      cows showed a lower number of secondary follicles (0.5+/-0.1 vs. 0.2+/-0.03).
      Quantitative analysis demonstrated a decrease in the density of blood vessels
      (6.30+/-1.08 vs. 4.68+/-0.28) expressed as ratio of vascular bed/total area) and
      a higher incidence of fibrous stroma (1.60+/-0.99 vs. 6.04+/-3.08 expressed as
      ratio of connective tissue/total area) in the cortical area of the most affected
      animals. Finally, the level of GDF-9 protein within the oocytes of different
      follicle size was lower in the animals with the severe form of chronic mastitis
      (1.34+/-0.05 vs. 0.78+/-0.21 expressed as arbitrary units). In conclusion,
      decreased fertility of cows with chronic mastitis takes place through an effect
      on the ovary altering the dynamics of folliculogenesis. Within the ovary, this
      implies a reduction of the vascular bed and an increase in the fibrotic tissue
      together with a direct effect on oocyte-specific factors as GDF-9, all of which
      are essential regulatory elements of folliculogenesis.

PMID- 22459836
TI  - Effect of intrauterine dextrose or antibiotic therapy on reproductive performance
      of lactating dairy cows diagnosed with clinical endometritis.
AB  - The objectives of this study were to assess the responses to treatments (clinical
      cure and cow survival 14 d posttherapy) of cows with clinical endometritis (CE)
      that received intrauterine infusion of a hypertonic solution of 50% dextrose
      (DEX) or subcutaneous ceftiofur crystalline free acid (CCFA) and subsequent
      pregnancy per artificial insemination (P/AI) in cows with CE compared with cows
      without CE. Cows (n=760) from 2 dairy herds were screened for CE using
      vaginoscopy and measurement of cervix diameters [exam 1; 26+/-3 d in milk (DIM)].
      Cows with vaginal discharge scores of 2 or 3 (scale 0-3) were stratified by
      parity and randomly allocated into 1 of 3 treatment groups: (1) intrauterine
      infusion (~200 mL) of 50% DEX solution (n=79); (2) 6.6 mg/kg single-dose of
      subcutaneous administration of CCFA (n=75); or (3) untreated control animals
      (CON, n=83). Fourteen days posttherapy (at 40+/-3 DIM), cows with CE were re
      examined (exam 2; 40+/-3 DIM) to assess the response to treatments. All cows were
      presynchronized with 2 injections of PGF(2alpha) given 14 d apart (starting at
      26+/-3 DIM) followed by Ovsynch (OV; GnRH-7 d-PGF-56 h-GnRH 16 h-timed-AI) 12 to
      14 d later. Cows displaying signs of standing estrus any time during the protocol
      were inseminated, whereas the remaining cows were subjected to timed AI 16 h
      after the second GnRH of OV. Pregnancy diagnosis was performed via transrectal
      ultrasonography at 39+/-3d post-AI followed by pregnancy reconfirmation 30 d
      after the first pregnancy diagnosis. Uterine swabs revealed that Arcanobacterium
      pyogenes and Escherichia coli were the most predominant bacteria isolated at the
      time of treatments. Mortality within 14 d posttherapy was not different among
      treatment groups. Cows with CE had greater cervical diameter at exam 1 and
      decreased P/AI compared with cows without CE. Treatment with CCFA or DEX
      increased the proportion of cows with clear vaginal discharge (score 0; clinical
      cure) 14 d posttherapy compared with CON cows. Pregnancy per AI from DEX (29.8+/
      4%) cows tended to differ from that of CON (21.1+/-4%) or CCFA cows (19.7+/-4%),
      but it resulted in similar P/AI as those cows without CE (39.1+/-2%). The use of
      intrauterine DEX alone or as an adjunct of antibiotic therapy for the treatment
      of CE needs further investigation.

PMID- 22459837
TI  - Intramammary infections and teat canal colonization with coagulase-negative
      staphylococci after postmilking teat disinfection: species-specific responses.
AB  - Coagulase-negative staphylococci (CNS) are the most common pathogens associated
      with intramammary infections (IMI) in dairy cows. We hypothesized that
      postmilking teat disinfection would reduce microbial colonization of the teat
      canal and thus reduce the prevalence of IMI caused by certain CNS species. The
      efficacy of iodine postmilking teat dip was tested against CNS colonization of
      the teat canal, and incidence of IMI was measured. Using an udder-half model, 43
      Holstein cows at the Washington State University Dairy were enrolled in the
      trial; postmilking teat dip was applied to one udder-half, treatment (TX), and
      the remaining half was an undipped control (CX). Teat canal swabbing and mammary
      quarter milk samples were taken in duplicate once a week for 16 wk for microbial
      culture. Isolates from agar cultures were presumptively identified as CNS and
      then speciated using PCR-RFLP and agarose gel electrophoresis. Colonization of
      the teat canal and IMI by CNS were assessed. Thirty CNS IMI were diagnosed and
      the number of new IMI in CX quarters (21) was significantly greater than that in
      TX mammary quarters (9). The majority of CNS IMI were caused by Staphylococcus
      chromogenes (30%) and Staphylococcus xylosus (40%), and the latter were
      appreciably reduced by teat dip. Except for S. xylosus, an association was
      observed between teat canal colonization and IMI by all CNS species in this
      study, in which the majority of IMI were preceded by teat canal colonization. The
      total number of CNS IMI was greater for CX group cows compared with TX group
      cows. However, the effect of disinfection on IMI did not appear to be the same
      for all CNS species.

PMID- 22459838
TI  - Minimum inhibitory concentrations of Staphylococcus aureus recovered from
      clinical and subclinical cases of bovine mastitis.
AB  - Antimicrobials are often used for treatment of bovine mastitis and the
      possibility of selection for resistant bacteria must be considered. The
      objectives of this study were to determine the minimum inhibitory concentration
      of Staphylococcus aureus recovered from cases of clinical and subclinical bovine
      mastitis, and to determine the prevalence of multidrug resistance in this
      population. Milk samples were collected from cows on commercial dairy herds
      (n=13), including quarters (n=1,574) of cows with subclinical mastitis cases, and
      cows experiencing clinical mastitis cases (n=608). Selected Staph. aureus
      isolates, obtained from clinical (n=58) and subclinical (n=58) mastitis cases,
      were used to determine minimum inhibitory concentrations of 12 selected
      antimicrobials. Of Staph. aureus isolates tested, 87 (75%) did not exhibit
      resistance to any antimicrobial, 28 (24.1%) exhibited resistance to 1 (n=21) or 2
      (n=7) classes of antimicrobials, and 1 (0.9%) exhibited multidrug resistance. All
      Staph. aureus (clinical and subclinical cases) were inhibited by the range of
      concentrations tested for ceftiofur and oxacillin. Moreover, no isolates obtained
      from clinical mastitis cases exhibited resistance to cephalothin, penicillin
      novobiocin, or sulfadimethoxine. Of isolates, 3 exhibited resistance to
      enrofloxacin. Of isolates exhibiting resistance to more than 1 antimicrobial,
      independent of antimicrobial class, the combination of erythromycin and
      tetracycline, and ampicillin and penicillin accounted for the majority of
      resistance. Of isolates tested, 19% were resistant to tetracycline and 14% were
      resistant to penicillin. Survival curves of Staph. aureus relative to minimum
      inhibitory concentration demonstrated heterogeneity among case types for
      ceftiofur, cephalothin, and erythromycin. Multidrug resistance was identified in
      only 1 isolate obtained from a single farm.

PMID- 22459839
TI  - Herd-level association between antimicrobial use and antimicrobial resistance in
      bovine mastitis Staphylococcus aureus isolates on Canadian dairy farms.
AB  - Surveillance of antimicrobial use and resistance is needed to manage
      antimicrobial resistance in bacteria. In this study, data were collected on
      antimicrobial use and resistance in Staphylococcus aureus (n=562), isolated from
      intramammary infections and (sub)clinical mastitis cases on 89 dairy farms in 4
      regions of Canada [Alberta, Ontario, Quebec, and the Maritime Provinces (Prince
      Edward Island, Nova Scotia, and New Brunswick)]. Dairy producers were asked to
      deposit empty drug containers into specially provided receptacles, and
      antimicrobial drug use rate was calculated to quantify antimicrobial use. Minimum
      inhibitory concentrations were determined using the Sensititer bovine mastitis
      plate system (TREK Diagnostic Systems Inc., Cleveland, OH), containing
      antimicrobials commonly used for mastitis treatment and control. Multivariable
      logistic regression models were built to determine herd-level risk factors of
      penicillin, ampicillin, pirlimycin, penicillin-novobiocin combination,
      tetracycline and sulfadimethoxine resistance in Staph. aureus isolates.
      Intramammary administration of the penicillin-novobiocin combination for dry cow
      therapy was associated with penicillin and ampicillin resistance [odds ratio
      (OR): 2.17 and 3.10, respectively]. Systemic administration of penicillin was
      associated with penicillin resistance (OR: 1.63). Intramammary administration of
      pirlimycin for lactating cow mastitis treatment was associated with pirlimycin
      resistance as well (OR: 2.07). Average herd parity was associated with ampicillin
      and tetracycline resistance (OR: 3.88 and 0.02, respectively). Average herd size
      was also associated with tetracycline resistance (OR: 1.02). Dairy herds in the
      Maritime region had higher odds of penicillin and lower odds of ampicillin
      resistance than dairy herds in Quebec (OR: 2.18 and 0.19, respectively). Alberta
      dairy herds had lower odds of ampicillin and sulfadimethoxine resistance than
      dairy herds in Quebec (OR: 0.04 and 0.08, respectively). Ontario dairy herds had
      lower odds of tetracycline and sulfadimethoxine resistance than dairy herds in
      Quebec (OR: 0.05 and 0.33, respectively). Herd-level use of certain
      antimicrobials administered for mastitis treatment and control, such as
      intramammary penicillin and pirlimycin as well as systemically administered
      penicillin and florfenicol, was positively associated with antimicrobial
      resistance in bovine mastitis pathogens in the field conditions. Differences in
      antimicrobial resistance outcomes across 4 regions of Canada were observed.

PMID- 22459840
TI  - Effect of dietary protein concentration on ammonia and greenhouse gas emitting
      potential of dairy manure.
AB  - Two experiments were conducted to investigate the effect of dietary crude protein
      concentration on ammonia (NH(3)) and greenhouse gas (GHG; nitrous oxide, methane,
      and carbon dioxide) emissions from fresh dairy cow manure incubated in a
      controlled environment (experiment 1) and from manure-amended soil (experiment
      2). Manure was prepared from feces and urine collected from lactating Holstein
      cows fed diets with 16.7% (DM basis; HCP) or 14.8% CP (LCP). High-CP manure had
      higher N content and proportion of NH(3)- and urea-N in total manure N than LCP
      manure (DM basis: 4.4 vs. 2.8% and 51.4 vs. 30.5%, respectively). In experiment
      1, NH(3) emitting potential (EP) was greater for HCP compared with LCP manure
      (9.20 vs. 4.88 mg/m(2) per min, respectively). The 122-h cumulative NH(3)
      emission tended to be decreased 47% (P=0.09) using LCP compared with HCP manure.
      The EP and cumulative emissions of GHG were not different between HCP and LCP
      manure. In experiment 2, urine and feces from cows fed LCP or HCP diets were
      mixed and immediately applied to lysimeters (61*61*61 cm; Hagerstown silt loam;
      fine, mixed, mesic Typic Hapludalf) at 277 kg of N/ha application rate. The
      average NH(3) EP (1.53 vs. 1.03 mg/m(2) per min, respectively) and the area under
      the EP curve were greater for lysimeters amended with HCP than with LCP manure.
      The largest difference in the NH(3) EP occurred approximately 24 h after manure
      application (approximately 3.5 times greater for HCP than LCP manure). The 100-h
      cumulative NH(3) emission was 98% greater for HCP compared with LCP manure (7,415
      vs. 3,745 mg/m(2), respectively). The EP of methane was increased and that of
      carbon dioxide tended to be increased by LCP compared with HCP manure. The
      cumulative methane emission was not different between treatments, whereas the
      cumulative carbon dioxide emission was increased with manure from the LCP diet.
      Nitrous oxide emissions were low in this experiment and did not differ between
      treatments. In the conditions of these experiments, fresh manure from dairy cows
      fed a LCP diet had substantially lower NH(3) EP, compared with manure from cows
      fed a HCP diet. The LCP manure increased soil methane EP due to a larger mass of
      manure added to meet plant N requirements compared with HCP manure. These results
      represent effects of dietary protein on NH(3) and GHG EP of manure in controlled
      laboratory conditions and do not account for environmental factors affecting
      gaseous emissions from manure on the farm.

PMID- 22459841
TI  - Effects of feeding increasing dietary levels of high oleic or regular sunflower
      or linseed oil on fatty acid profile of goat milk.
AB  - In this work, the effects of increasing amounts of 3 plant oils in diets on the
      fatty acid (FA) profile of goat milk were studied. The study consisted of 3
      experiments, one per oil tested (linseed oil, LO; high oleic sunflower oil,
      HOSFO; and regular sunflower oil, RSFO). The 3 experiments were conducted
      successively on 12 Malaguena goats, which were assigned at random to 1 of 4
      treatments: 0, 30, 48, and 66 (H) g of added oil/d. A basal diet made of alfalfa
      hay and pelleted concentrate (33:67) was used in all of the experiments. For each
      animal, milk samples collected after 15 d on treatments were analyzed for fat,
      protein, lactose, and FA composition, whereas individual milk yield was measured
      the last 3 d of each experiment. Oil supplementation affected neither dry matter
      intake nor milk production traits. Increasing the oil supplementation decreased
      the content of saturated FA (especially 16:0) in milk fat and increased mono- and
      polyunsaturated FA in a linear manner. Vaccenic acid content linearly increased
      with the oil supplementation by 370, 217, and 634% to 5.32, 2.66, and 5.09 g/100
      g of total FA methyl esters with the H diet in LO, HOSFO, and RSFO experiments,
      respectively. Rumenic acid content linearly increased with LO and RSFO
      supplementation by 298 and 354% from 0.53 and 0.41 g/100 g of total FA methyl
      esters with the 0 g of added oil/d diet. The content of trans-10-18:1 was not
      affected by LO supplementation but showed an increasing linear trend with HOSFO
      supplementation and linearly increased with RSFO supplementation. The ratio of n
      6 to n-3 polyunsaturated FA in milk fat was decreased by about 70% with the H
      diet in the LO experiment and it was increased by 54 and 82% with the H diet in
      the HOSFO and RSFO experiments. In conclusion, LO supplementation in this work
      seemed to be the most favorable alternative compared with HOSFO or RSFO
      supplementation.

PMID- 22459842
TI  - Rapeseed or linseed supplements in grass-based diets: effects on dairy
      performance of Holstein cows over 2 consecutive lactations.
AB  - The aim of this study was to evaluate the effects of long-term supplementation
      with different oilseeds rich in 18:1 cis-9 or 18:3n-3 fatty acids on dairy cow
      performance over 2 consecutive lactations. This trial involved 58 Holstein cows
      during the first year and 35 during the second year. During the first 5 wk of the
      first year, all of the cows were fed the same diet; after a 4-wk transition
      period, the cows received 1 of 5 treatments for 2 consecutive lactations,
      including the dry period. Their basal diet was supplemented or not with extruded
      linseeds or with different forms of rapeseeds: extruded seeds, cold-pressed fat
      rich meal, or whole unprocessed seeds. Oilseed amount was calculated to provide
      2.5 to 3.0% additional oil in ration dry matter. Cows were fed a grass-based diet
      (75% grass silage and 25% hay) during indoor periods and grazed during outdoor
      periods. For the first year of experimentation, oilseed supplementation had no
      effect on milk, fat, protein, and lactose yields, body weight, or body condition
      score compared with the control treatment (no oilseed supplementation). During
      the indoor period, extruded linseed tended to decrease dry matter intake (-1.5
      kg/d), whereas all of the oilseed treatments decreased milk protein content
      without changing protein yield. Cold-pressed fat-rich rapeseed meal decreased
      milk protein content independently of the period (-0.29 and -0.19 g/100 g for
      indoor and outdoor periods, respectively), and whole unprocessed rapeseed
      increased milk fat content during the outdoor period (+0.53 g/100 g compared with
      the control treatment). During the second year of experimentation, the effects of
      oilseed supplementation during the outdoor period were similar to those observed
      during the first outdoor period, but the effects of oilseed supplementation
      differed between the 2 indoor periods. This was likely due to changes in forage
      quality and composition and percentage in the ration of the concentrate mixtures.
      Thus, the effects of oilseed supplementation depended on oilseed nature (rapeseed
      or linseed) and form (extruded seeds, cold-pressed fat-rich meal, or whole
      unprocessed seeds) in interaction with the type of basal diet (grass silage and
      hay or pasture) and the concentrate composition and percentage in the ration.
      Effects were stable during the first indoor period, repeatable between the 2
      outdoor periods, and were similar to effects observed previously in short-term
      studies (1 to 3 mo).

PMID- 22459843
TI  - Effects of grain, fructose, and histidine on ruminal pH and fermentation products
      during an induced subacute acidosis protocol.
AB  - The effects of grain, fructose, and histidine on ruminal pH and fermentation
      products were studied in dairy cattle during an induced subacute acidosis
      protocol. Thirty Holstein heifers were randomly allocated to 5 treatment groups:
      (1) control (no grain); (2) grain [fed at a crushed triticale dry matter intake
      (DMI) of 1.2% of body weight (BW)]; (3) grain (0.8% of BW DMI)+fructose (0.4% of
      BW DMI); (4) grain (1.2% of BW DMI)+histidine (6 g/head); and (5) grain (0.8% of
      BW DMI)+fructose (0.4% of BW DMI)+histidine (6 g/head) in a partial factorial
      arrangement. Heifers were fed 1 kg of grain daily with ad libitum access to
      ryegrass silage and alfalfa hay for 10 d. Feed was withheld for 14 h before
      challenge day, on which heifers were fed 200 g of alfalfa hay and then the
      treatment diets immediately thereafter. Rumen samples were collected 5 min after
      diet ingestion, 60 min later, and at 3 subsequent 50-min intervals. Grain
      decreased ruminal pH and increased ammonia, total volatile fatty acid (VFA),
      acetate, butyrate, propionate, and valerate concentrations compared with
      controls. The addition of grain had no effect on ruminal D- and L-lactate
      concentrations. Fructose markedly decreased ruminal pH and markedly increased D-
      and L-lactate concentrations. Fructose increased total VFA and butyrate and
      decreased valerate concentrations. Although histidine did not have a marked
      effect on ruminal fermentation, increased concentrations of histamine were
      observed following feeding. This study demonstrates that the substitution of some
      grain for fructose can lower ruminal pH and increase VFA and lactate
      concentrations, warranting further investigation into the role of sugars on the
      risk of acidosis in dairy cattle.

PMID- 22459844
TI  - Protein and energy intakes affected amino acid concentrations in plasma, muscle,
      and liver, and cell signaling in the liver of growing dairy calves.
AB  - The nutrient content of and feeding recommendations for milk replacers (MR) vary
      widely in North America, and acceleration of growth through manipulation of
      protein and energy intakes can reduce rearing costs of dairy operations. The
      effects of varying the protein and energy intake of MR on metabolite
      concentrations in plasma, liver, and muscle and the phosphorylation activity of
      protein kinase B (AKT) and ribosomal protein S6 (rpS6) cell signals in liver and
      muscle were assessed. Twenty-four newborn Holstein calves were fed 1 of 4 MR for
      9 wk (n=6/treatment): (1) a 20% crude protein (CP), 20% fat MR fed at 441 g of
      dry matter (DM)/d (CON); (2) a high-protein, medium-fat MR (HPMF; 28% CP, 20%
      fat) fed at 951 g of DM/d; (3) a high-protein, high-fat MR (HPHF; 27% CP, 28%
      fat) fed at 951 g of DM/d; and (4) HPHF fed at 1,431 g of DM/d (HPHF+). Water and
      starter (20% CP, 1.43% fat) were offered ad libitum and calves were fed MR twice
      daily. Plasma samples were obtained at 1, 5, and 9 wk of age. Calves were not
      weaned and were slaughtered after the last blood sampling. Liver and muscle
      tissues were collected and analyzed for metabolite concentrations and cell
      signaling activity. Calves fed all treatments had lower plasma concentrations of
      Phe and Tyr, and a trend for lower Leu, but greater concentrations of Thr
      relative to calves fed CON. Calves fed all treatments had increased muscle
      concentrations of Met and muscle to plasma ratios of Phe, Tyr, and branched-chain
      amino acids compared with CON. All treatments increased liver to plasma ratios of
      Phe and Tyr but diminished the ratios of Met compared with CON. Phosphorylation
      of protein kinase B was not affected by treatment; however, relative to calves
      fed HPHF, HPMF and HPHF+ diets increased phosphorylation ratios of ribosomal
      protein S6 in the liver. Therefore, the changes in plasma and tissue
      concentrations and plasma to tissue ratios of amino acids were associated with
      enhanced growth rates. However, cell signaling activity was not consistent with
      accelerated growth in calves fed treatments with increased contents of energy and
      protein possibly due to confounding effects of diet (MR + starter) or fasting
      before tissue harvesting. Muscle concentrations of Met might have a regulatory
      role in protein synthesis in rapidly growing calves fed high levels of CP and
      energy.

PMID- 22459845
TI  - A ring test of in vitro neutral detergent fiber digestibility: analytical
      variability and sample ranking.
AB  - In vitro neutral detergent fiber (NDF) digestibility (NDFD) is an empirical
      measurement of fiber fermentability by rumen microbes. Variation is inherent in
      all assays and may be increased as multiple steps or differing procedures are
      used to assess an empirical measure. The main objective of this study was to
      evaluate variability within and among laboratories of 30-h NDFD values analyzed
      in repeated runs. Subsamples of alfalfa (n=4), corn forage (n=5), and grass (n=5)
      ground to pass a 6-mm screen passed a test for homogeneity. The 14 samples were
      sent to 10 laboratories on 3 occasions over 12 mo. Laboratories ground the
      samples and ran 1 to 3 replicates of each sample within fermentation run and
      analyzed 2 or 3 sets of samples. Laboratories used 1 of 2 NDFD procedures: 8 labs
      used procedures related to the 1970 Goering and Van Soest (GVS) procedure using
      fermentation vessels or filter bags, and 2 used a procedure with preincubated
      inoculum (PInc). Means and standard deviations (SD) of sample replicates within
      run within laboratory (lab) were evaluated with a statistical model that included
      lab, run within lab, sample, and lab * sample interaction as factors. All factors
      affected mean values for 30-h NDFD. The lab * sample effect suggests against a
      simple lab bias in mean values. The SD ranged from 0.49 to 3.37% NDFD and were
      influenced by lab and run within lab. The GVS procedure gave greater NDFD values
      than PInc, with an average difference across all samples of 17% NDFD. Because of
      the differences between GVS and PInc, we recommend using results in contexts
      appropriate to each procedure. The 95% probability limits for within-lab
      repeatability and among-lab reproducibility for GVS mean values were 10.2 and
      13.4%, respectively. These percentages describe the span of the range around the
      mean into which 95% of analytical results for a sample fall for values generated
      within a lab and among labs. This degree of precision was supported in that the
      average maximum difference between samples that were not declared different by
      means separation was 4.4% NDFD. Although the values did not have great precision,
      GVS labs were able to reliably rank sample data in order of 30-h NDFD (Spearman
      correlation coefficient = 0.93) with 80% of the rankings correct or off by only 1
      ranking. A relative ranking system for NDFD could reduce the effect of within-
      and among-lab variation in numeric values. Such a system could give a more
      accurate portrayal of the comparative values of samples than current numeric
      values imply.

PMID- 22459846
TI  - Development and evaluation of equations in the Cornell Net Carbohydrate and
      Protein System to predict nitrogen excretion in lactating dairy cows.
AB  - Nitrogen excretion is of particular concern on dairy farms, not only because of
      its effects on water quality, but also because of the subsequent release of gases
      such as ammonia to the atmosphere. To manage N excretion, accurate estimates of
      urinary N (UN) and fecal N (FN) are needed. On commercial farms, directly
      measuring UN and FN is impractical, meaning that quantification must be based on
      predictions rather than measured data. The purpose of this study was to use a
      statistical approach to develop equations and evaluate the Cornell Net
      Carbohydrate and Protein System's (CNCPS) ability to predict N excretion in
      lactating dairy cows, and to compare CNCPS predictions to other equations in the
      literature. Urinary N was over-predicted by the CNCPS due to inconsistencies in N
      accounting within the model that partitioned more N to feces than urine, although
      predicted total N excretion was reasonable. Data to refine model predictions were
      compiled from published studies (n=32) that reported total collection N balance
      results. Considerable care was taken to ensure the data included in the
      development data set (n=104) accounted for >90% of the N intake (NI). Unaccounted
      N for the compiled data set was 1.47+/-4.60% (mean +/- SD). The results showed
      that FN predictions could be improved by using a modification of a previously
      published equation: FN (g/d) = [[NI (g/kg of organic matter) * (1 - 0.842)] + 4.3
      * organic matter intake (kg/d)] * 1.20, which, when evaluated against the
      compiled N balance data, had a squared coefficient of determination based on a
      mean study effect R(MP)(2) of 0.73, concurrent correlation coefficient (CCC) of
      0.83 and a root mean square error (RMSE) of 10.38 g/d. Urinary N is calculated in
      the CNCPS as the difference between NI and other N excretion and losses.
      Incorporating the more accurate FN prediction into the current CNCPS framework
      and correcting an internal calculation error considerably improved UN predictions
      (RMSE=12.73 g/d, R(MP)(2)=0.86, CCC=0.90). The changes to FN and UN translated
      into an improved prediction of total manure N excretion (RMSE=12.42 g/d,
      R(MP)(2)=0.96, CCC=0.97) and allows nutritionists and farm advisors to evaluate
      these factors during the ration formulation process.

PMID- 22459847
TI  - Rumen and milk odd- and branched-chain fatty acid proportions are minimally
      influenced by ruminal volatile fatty acid infusions.
AB  - The objective of this study was to determine if ruminally infusing volatile fatty
      acid (VFA) increased concentration of their homologous odd- and branched-chain
      fatty acid (OBCFA) in rumen contents and milk. The influence of VFA on dry matter
      intake (DMI), blood metabolites, and blood insulin was also evaluated. Four mid
      lactation cows were assigned to a 4*4 Latin square design with 48-h periods.
      Infusion treatments were acetate (AC), propionate (PR), isovalerate (IV), and
      anteisovalerate (AIV). Infusions began (time = 0) 5.5 h before feeding at 17.4
      mmol of VFA/min and were terminated at 18 h. Infusions rates were well above
      physiological levels for IV and AIV. Surprisingly, the greatest differences in
      rumen OBCFA were increases in rumen liquid iso C15:0 and nonbranched C17:0 for
      AIV. In addition, infusing AIV increased anteiso C15:0 and anteiso C17:0 in rumen
      solid contents. Infusing IV increased iso C15:0 in both rumen solids and milk.
      Propionate increased milk C15:0 and C17:0. Both gluconeogenic compounds, PR and
      AIV, had similar proportions of milk C15:0, which was greater than that obtained
      with AC and IV. Rumen and blood VFA were as expected, with increased
      concentrations of the VFA present in the infusate. At 23 h, and consistently
      throughout infusions, DMI was similar for AC compared with PR and for AIV
      compared with IV. Both IV and AIV decreased DMI and energy balance; however, only
      IV increased plasma nonesterified fatty acids (121, 78, 172, and 102 mM for AC,
      AIV, IV, and PR), increased beta-hydroxybutyrate (10.8, 5.9, 51.9, 5.4 mg/dL for
      AC, AIV, IV, and PR), and reduced plasma glucose (56.3, 59.1, 31.9, and 64.3
      mg/dL for AC, AIV, IV, and PR). Rumen and milk OBCFA responses were minimal
      following infusion of large amounts of IV and AIV, suggesting limited use of IV,
      and AIV for de novo OBCFA synthesis, either pre- or postabsorption. Minor
      increases in milk odd-chain fatty acids following large doses of ruminal PR
      support the presence of postabsorptive synthesis of these milk odd-chain fatty
      acids.

PMID- 22459848
TI  - Effect of bromochloromethane on methane emission, rumen fermentation pattern,
      milk yield, and fatty acid profile in lactating dairy goats.
AB  - Several technologies have been tested to reduce enteric methanogenesis, but very
      few have been successfully used in practical conditions for livestock.
      Furthermore, the consequences of reduced rumen methane production on animal
      performance and milk quality are poorly understood. The aim of this work was to
      investigate the effect of feeding bromochloromethane (BCM), a halogenated
      aliphatic hydrocarbon with potential antimethanogenic activity, to dairy goats on
      rumen methane production, fermentation pattern, the abundance of major microbial
      groups, and on animal performance and milk composition. Eighteen goats were
      allocated to 2 experimental groups of 9 animals each: treated (BCM+) or not (BCM
      ) with 0.30 g of BCM/100 kg of body weight per day. The BCM was administered per
      os in 2 equal doses per day from parturition to 2 wk postweaning (10 wk). After
      weaning, methane emissions were recorded over 2 consecutive days (d 57 and 58 on
      treatment) in polycarbonate chambers. On d 59, individual rumen fluid samples
      were collected for volatile fatty acid (VFA) analysis and quantification of
      bacterial, protozoal, and archaeal numbers by real-time PCR. On d 69 and 70,
      daily milk production was recorded and samples were collected for determination
      of fat, protein, lactose, casein, and total solids concentration by infrared
      spectrophotometry, and fatty acid composition by gas chromatography. Treatment
      with BCM reduced methane production by 33% (21.6 vs. 14.4 L/kg of DMI) compared
      with nontreated animals, although it did not affect the abundance of rumen
      bacteria, protozoa, and total methanogenic archaea. The observed improvement in
      the efficiency of digestive processes was accompanied by a 36% increase in milk
      yield, probably due to the more propionic type of rumen fermentation and an
      increase in VFA production. The increase in milk yield was not accompanied by any
      changes in the concentrations or yields of fat, protein, or lactose. Despite the
      substantial decrease in methane production, only minor changes in milk fatty acid
      profile were observed, suggesting that ruminal biohydrogenation pathways were not
      affected. Compounds that influence terminal biochemical pathways for methane
      production deserve further development for future application in the dairy goat
      sector.

PMID- 22459849
TI  - Chromium propionate enhances insulin sensitivity in growing cattle.
AB  - Thirty-six Angus and Angus*Simmental heifers, averaging 291 kg, were used to
      determine the effects of dietary Cr, in the form of Cr propionate (Cr Prop), on
      glucose metabolism and serum insulin concentrations following glucose
      administration. Heifers were stratified by body weight (BW) within a breed and
      randomly assigned to treatments. Treatments consisted of 0, 3, 6, or 9 mg of
      supplemental Cr/d from Cr Prop. Based on dry matter (DM) intakes, the daily doses
      of Cr were equivalent to 0.47, 0.94, and 1.42 mg of supplemental Cr/kg of DM.
      Heifers were individually fed a corn silage-based diet at a level of 2% of BW.
      Each heifer was also fed 0.45 kg of a ground corn supplement daily that served as
      a carrier for supplemental Cr. Glucose tolerance tests were performed on d 44 of
      the study. Glucose was infused via jugular catheters at a level of 0.45 g/kg of
      BW(0.75) over a course of 1 to 2 min. Blood samples were collected at -10, 0, 5,
      10, 15, 30, 45, 60, 90, 120, 150, and 180 min relative to glucose dosing for
      glucose and insulin determination. Area under the glucose response curve was
      lower (1,603 vs. 1,964 mg/dL per minute) in heifers supplemented with Cr from 0
      to 45 min following glucose challenge. Serum insulin concentrations were lower in
      Cr-supplemented heifers than in controls following glucose infusion. The molar
      ratio of insulin to glucose was also lower in Cr-supplemented heifers relative to
      controls. Serum insulin and serum insulin to glucose ratios did not differ among
      heifers supplemented with 3, 6, or 9 mg of Cr/d. Results indicate that Cr Prop
      supplementation increased tissue sensitivity to insulin in growing heifers. Based
      on insulin sensitivity, Cr requirements (as Cr Prop) of growing heifers can be
      met by supplementing with 3 mg of Cr/d or 0.47 mg of Cr/kg of DM.

PMID- 22459850
TI  - Interaction of unsaturated fat or coconut oil with monensin in lactating dairy
      cows fed 12 times daily. I. Protozoal abundance, nutrient digestibility, and
      microbial protein flow to the omasum.
AB  - Monensin (tradename: Rumensin) should reduce the extent of amino acid deamination
      in the rumen, and supplemental fat should decrease protozoal abundance and
      intraruminal N recycling. Because animal-vegetable (AV) fat can be
      biohydrogenated in the rumen and decrease its effectiveness as an anti-protozoal
      agent, we included diets supplemented with coconut oil (CNO) to inhibit protozoa.
      In a 6 * 6 Latin square design with a 2 * 3 factorial arrangement of treatments,
      6 rumen-cannulated cows were fed diets without or with Rumensin (12 g/909 kg) and
      either no fat (control), 5% AV fat, or 5% CNO. The log10 concentrations
      (cells/mL) of total protozoa were not different between control (5.97) and AV fat
      (5.95) but were decreased by CNO (4.79; main effect of fat source). Entodinium
      and Dasytricha decreased as a proportion of total cells from feeding CNO, whereas
      Epidinium was unchanged in total abundance and thus increased proportionately.
      Total volatile fatty acid concentration was not affected by diet, but the
      acetate:propionate ratio decreased for CNO (1.85) versus control (2.95) or AV fat
      (2.58). Feeding CNO (23.8%) decreased ruminal neutral detergent fiber
      digestibility compared with control (31.1%) and AV fat (30.5%). The total-tract
      digestibility of NDF was lower for CNO (45.8%) versus control (57.0%) and AV fat
      (54.6%), with no difference in apparent organic matter digestibility (averaging
      69.8%). The omasal flows of microbial N and non-ammonia N were lower for CNO
      versus control and AV fat, but efficiency of microbial protein synthesis was not
      affected. The dry matter intake was 4.5 kg/d lower with CNO, which decreased milk
      production by 3.1 kg/d. Main effect means of dry matter intake and milk yield
      tended to decrease by 0.7 and 1.2 kg/d, respectively, when Rumensin was added.
      Both percentage and production of milk fat decreased for CNO (main effect of fat
      source). An interaction was observed such that AV decreased milk fat yield more
      when combined with Rumensin. Using large amounts of supplemental fat, especially
      CNO, to decrease abundance of protozoa requires further research to characterize
      benefits versus risks, especially when combined with Rumensin.

PMID- 22459851
TI  - Interaction of unsaturated fat or coconut oil with monensin in lactating dairy
      cows fed 12 times daily. II. Fatty acid flow to the omasum and milk fatty acid
      profile.
AB  - Feeding animal-vegetable (AV) fat or medium-chain fatty acids (FA) to dairy cows
      can decrease ruminal protozoal counts. However, combining moderate to large
      amounts of AV fat with monensin (tradename: Rumensin, R) could increase the risk
      for milk fat depression (MFD), whereas it is not known if diets supplemented with
      coconut oil (CNO; rich in medium-chain FA) with R would cause MFD. In a 6 * 6
      Latin square design with a 2 * 3 factorial arrangement of treatments, 6 rumen
      cannulated cows were fed diets without or with R (12 g/909 kg) and either control
      (no fat), 5% AV fat, or 5% CNO. Diets were balanced to have 21.5% forage neutral
      detergent fiber, 16.8% crude protein, and 42% nonfiber carbohydrates. Omasal
      flows of FA were characterized by an increased percentage of trans 18:1 for AV
      fat and CNO diets compared with the control, a higher percentage of 12:0 and 14:0
      for CNO, and higher cis 18:1 for AV fat. Milk FA composition reflected the
      changes observed for omasal FA digesta flow. The de novo FA synthesis in the
      mammary gland was decreased by the main effects of R compared without R (averaged
      over fat treatments) and for added fat (AV fat and CNO) versus control (averaged
      over R). The percentages of 6:0, 8:0, and 10:0 in milk fat were lower for R and
      for AV fat and CNO compared with the control. The percentage of trans 18:1 FA in
      milk fat also higher for AV fat and CNO compared with the control. Against our
      hypotheses, the feeding of CNO did not prevent MFD, and few interactions between
      R and fat source were detected. The feeding of CNO did compromise ruminal
      biohydrogenation, with accumulation of trans 18:1 in the rumen and in milk fat.

PMID- 22459852
TI  - Conservation characteristics of corn ears and stover ensiled with the addition of
      Lactobacillus plantarum MTD-1, Lactobacillus plantarum 30114, or Lactobacillus
      buchneri 11A44.
AB  - The aim of this study was to investigate the effects of inoculating 3 contrasting
      lactic acid bacteria on the fermentation profile, estimated nutritive value, and
      aerobic stability of corn ears and stover produced under marginal growing
      conditions. Ears and stover were separated from whole-crop corn plants obtained
      from 3 replicate field blocks. Representative subsamples were precision chopped
      and allocated to 1 of the following treatments: an uninoculated control,
      Lactobacillus plantarum MTD-1 (LP1), L. plantarum 30114 (LP2), or Lactobacillus
      buchneri 11A44 (LB). Each bacterial additive was applied at a rate of 1 * 10(6)
      cfu/g of fresh herbage. Triplicate samples of each treatment were ensiled in
      laboratory silos at 15 degrees C for 3, 10, 35, or 130 d. No difference was
      observed between the dry matter recoveries of uninoculated ear or stover silages
      and silages made with LP1, and the aerobic stability of uninoculated ear and
      stover silages did not differ from silages made with LB. Stover silages made with
      LP2 and ensiled for 35 d had a lower proportion of lactic acid in total
      fermentation products compared with LP1. The aerobic stability and dry matter
      recovery of ear and stover silages in this study were not improved when made with
      LB, LP1, or LP2, due to the indigenous highly heterolactic fermentation that
      prevailed in the uninoculated ear and stover during 130-d ensilage.

PMID- 22459853
TI  - Use of a corn milling product in diets for dairy cows to alleviate milk fat
      depression.
AB  - Various diet formulation strategies were evaluated to alleviate milk fat
      depression using a corn milling product (CMP) that contained approximately 28%
      crude protein, 34% neutral detergent fiber (NDF), and 12% starch (dry basis). The
      control diet comprised mostly corn silage, alfalfa silage, corn grain, and
      soybean meal and contained approximately 22% forage NDF (fNDF), 28% total NDF,
      and 33% starch. Another diet included 25% CMP that replaced corn grain and
      soybean meal and contained 27% starch and 33% NDF. Two other diets included 25 or
      40% CMP that replaced forage and concentrate and contained 19 and 17% fNDF, 31
      and 32% total NDF, and 30 and 28% starch, respectively. Diets were fed to 16 mid
      lactation Holstein cows in 4 replicated 4 * 4 Latin squares. Milk fat percentage
      was low for the control diet (2.9%) but increased to 3.5% when cows were fed the
      diet with 25% CMP that replaced concentrate. Cows fed diets with 25 or 40% CMP
      that replaced forage and concentrate also had low milk fat percentages (3.0 and
      2.9%, respectively). Intake was lowest for cows fed the control diet. Milk yield
      was reduced when CMP replaced only concentrate but because of the substantial
      increase in milk fat, the yield of energy-corrected milk was greater. Calculated
      energy use (maintenance+milk+body weight change) divided by dry matter intake was
      similar for the control and for the diet in which CMP replaced only concentrate,
      but it decreased linearly as increasing amounts of CMP replaced both forage and
      concentrate. A quadratic equation using the ratio of dietary starch to fNDF was
      the best predictor of milk fat percentage (ratios >1.4 were associated with
      reduced milk fat). Overall, CMP was effective at alleviating milk fat depression
      when it replaced corn grain but not when it replaced forage and concentrate.

PMID- 22459854
TI  - Short communication: Relationship of carbohydrate molecular spectroscopic
      features to carbohydrate nutrient profiles in co-products from bioethanol
      production.
AB  - The objective of this study was to use diffuse reflectance infrared Fourier
      transform (DRIFT) molecular spectroscopy to investigate the relationship between
      carbohydrate (CHO) molecular structure spectral profiles (in terms of CHO
      molecular spectral peak area and height intensities) and CHO chemical profiles,
      CHO subfractions, energy values, and rumen fermentable organic matter supply in
      different grains and different types of dried distillers grains with solubles.
      The various CHO molecular spectral bands included A_Cell (peak area region and
      baseline ~1485-1188 cm(-1)), mainly associated with hemicellulosic and cellulosic
      compounds; A_1240 (peak area centered at ~1240 cm(-1) with region and baseline
      ~1292-1198 cm(-1)), mainly associated with cellulosic compounds; A_CHO (peak
      region and baseline ~1187-950 cm(-1)) associate with total CHO; A_928 (peak area
      centered at ~928 cm(-1) with region and baseline ~952-910 cm(-1)); and A_860
      (peak area centered at ~860 cm(-1) with region and baseline ~880-827 cm(-1)),
      mainly associated with nonstructural CHO; H_1415 (peak height centered at ~1415
      cm(-1) with baseline ~1485-1188 cm(-1)); and H_1370 (peak height at ~1370 cm(-1)
      with a baseline ~1485-1188 cm(-1)), mainly associated with structural CHO. No
      significant correlations were found among A_Cell, A_CHO, H_1415, and H_1370 with
      CHO chemical and nutrient profiles in the bioethanol co-products. However, CHO
      molecular spectral intensities of A_1240, A_928, and A_860 were strongly
      correlated with rapidly degradable CHO fraction (CB1), lowly degradable CHO
      fraction (CB2), and an unavailable CHO fraction (CC) and could be good
      indicators. In conclusion, the changes in CHO molecular structures during the
      processing for bioethanol production were highly associated with carbohydrate
      degradable subfractions in ruminants.

PMID- 22459855
TI  - Optimum multistage genomic selection in dairy cattle.
AB  - The availability of different single nucleotide polymorphism (SNP) chips and the
      development of imputation algorithms allow for multistage dairy cattle breeding
      schemes applying various genomic selection strategies. These SNP genotypes yield
      genomically estimated breeding values (GEBV) with different accuracies at
      different costs. Thus, the optimum allocation of investments to different
      selection paths and strategies to maximize the genetic gain per year (DeltaG(a))
      and its sensitivity to changes in cost and accuracies of GEBV is of great
      interest. This is even more relevant under the constraints of limited financial
      resources. With deterministic methods, optimum multistage breeding plans
      maximizing DeltaG(a) were identified in which selection could take place on GEBV
      derived from high-density (GEBV(HD)) and low-density (GEBV(LD)) SNP genotypes. To
      account for the uncertainty of cost and accuracies of GEBV, these parameters were
      varied in a semi-continuous manner. Overall breeding costs were limited to the
      crucial expenses of a traditional breeding program with 50 progeny-tested young
      bulls per year. Results clearly show that, in an optimal selection strategy,
      selection on GEBV(LD) is predominantly used for the identification of future bull
      dams but the main part of DeltaG(a) is still generated from selection of sires.
      The low selection intensity in the path dam to sire induced a higher sensitivity
      of DeltaG(a) to changes in cost and accuracies of GEBV(LD) compared with the same
      changes of GEBV(HD). On the contrary, the genetic gain generated from selection
      of males was only affected by changes in accuracies of GEBV(HD) but almost
      unaffected by any changes in cost. Thus, changes in cost and accuracies of
      GEBV(LD) put the most pressure on the breeding scheme structure to maintain a
      high DeltaG(a). Furthermore, genomic selection of bull dams produced by far the
      majority of breeding cost but the lowest genetic gain.

PMID- 22459856
TI  - Accuracy of genomic predictions of residual feed intake and 250-day body weight
      in growing heifers using 625,000 single nucleotide polymorphism markers.
AB  - Feed makes up a large proportion of variable costs in dairying. For this reason,
      selection for traits associated with feed conversion efficiency should lead to
      greater profitability of dairying. Residual feed intake (RFI) is the difference
      between actual and predicted feed intakes and is a useful selection criterion for
      greater feed efficiency. However, measuring individual feed intakes on a large
      scale is prohibitively expensive. A panel of DNA markers explaining genetic
      variation in this trait would enable cost-effective genomic selection for this
      trait. With the aim of enabling genomic selection for RFI, we used data from
      almost 2,000 heifers measured for growth rate and feed intake in Australia (AU)
      and New Zealand (NZ) genotyped for 625,000 single nucleotide polymorphism (SNP)
      markers. Substantial variation in RFI and 250-d body weight (BW250) was
      demonstrated. Heritabilities of RFI and BW250 estimated using genomic
      relationships among the heifers were 0.22 and 0.28 in AU heifers and 0.38 and
      0.44 in NZ heifers, respectively. Genomic breeding values for RFI and BW250 were
      derived using genomic BLUP and 2 bayesian methods (BayesA, BayesMulti). The
      accuracies of genomic breeding values for RFI were evaluated using cross
      validation. When 624,930 SNP were used to derive the prediction equation, the
      accuracies averaged 0.37 and 0.31 for RFI in AU and NZ validation data sets,
      respectively, and 0.40 and 0.25 for BW250 in AU and NZ, respectively. The
      greatest advantage of using the full 624,930 SNP over a reduced panel of 36,673
      SNP (the widely used BovineSNP50 array) was when the reference population
      included only animals from either the AU or the NZ experiment. Finally, the
      bayesian methods were also used for quantitative trait loci detection. On
      chromosome 14 at around 25 Mb, several SNP closest to PLAG1 (a gene believed to
      affect stature in humans and cattle) had an effect on BW250 in both AU and NZ
      populations. In addition, 8 SNP with large effects on RFI were located on
      chromosome 14 at around 35.7 Mb. These SNP may be associated with the gene NCOA2,
      which has a role in controlling energy metabolism.

PMID- 22459857
TI  - A comparison of partial least squares (PLS) and sparse PLS regressions in genomic
      selection in French dairy cattle.
AB  - Genomic selection involves computing a prediction equation from the estimated
      effects of a large number of DNA markers based on a limited number of genotyped
      animals with phenotypes. The number of observations is much smaller than the
      number of independent variables, and the challenge is to find methods that
      perform well in this context. Partial least squares regression (PLS) and sparse
      PLS were used with a reference population of 3,940 genotyped and phenotyped
      French Holstein bulls and 39,738 polymorphic single nucleotide polymorphism
      markers. Partial least squares regression reduces the number of variables by
      projecting independent variables onto latent structures. Sparse PLS combines
      variable selection and modeling in a one-step procedure. Correlations between
      observed phenotypes and phenotypes predicted by PLS and sparse PLS were similar,
      but sparse PLS highlighted some genome regions more clearly. Both PLS and sparse
      PLS were more accurate than pedigree-based BLUP and generally provided lower
      correlations between observed and predicted phenotypes than did genomic BLUP.
      Furthermore, PLS and sparse PLS required similar computing time to genomic BLUP
      for the study of 6 traits.

PMID- 22459858
TI  - Makeup of the genetic correlation between milk production traits using genome
      wide single nucleotide polymorphism information.
AB  - The correlated responses between traits may differ depending on the makeup of
      genetic covariances, and may differ from the predictions of polygenic
      covariances. Therefore, the objective of the present study was to investigate the
      makeup of the genetic covariances between the well-studied traits: milk yield,
      fat yield, protein yield, and their percentages in more detail. Phenotypic
      records of 1,737 heifers of research farms in 4 different countries were used
      after homogenizing and adjusting for management effects. All cows had a genotype
      for 37,590 single nucleotide polymorphisms (SNP). A bayesian stochastic search
      variable selection model was used to estimate the SNP effects for each trait.
      About 0.5 to 1.0% of the SNP had a significant effect on 1 or more traits;
      however, the SNP without a significant effect explained most of the genetic
      variances and covariances of the traits. Single nucleotide polymorphism
      correlations differed from the polygenic correlations, but only 10 regions were
      found with an effect on multiple traits; in 1 of these regions the DGAT1 gene was
      previously reported with an effect on multiple traits. This region explained up
      to 41% of the variances of 4 traits and explained a major part of the correlation
      between fat yield and fat percentage and contributes to asymmetry in correlated
      response between fat yield and fat percentage. Overall, for the traits in this
      study, the infinitesimal model is expected to be sufficient for the estimation of
      the variances and covariances.

PMID- 22459859
TI  - Incidences of and genetic parameters for mastitis, claw disorders, and common
      health traits recorded in dairy cattle contract herds.
AB  - Test-day records for protein yield, protein percent, fat percent and somatic cell
      score combined with diagnoses for health traits from 19,870 Holstein cows kept in
      9 large-scale contract herds in the region of Thuringia, Germany, were used to
      infer genetic parameters. From an electronic database system for recording
      diagnoses, 15 health disorders with highest incidences were extracted and grouped
      into the following 5 disease categories: claw disorders, mastitis, female
      fertility, metabolism, and ectoparasites. In a bayesian approach, threshold
      methodology was applied for binary distributed health disorders and linear models
      were used for gaussian test-day observations. Variances and variance ratios for
      health disorders were from univariate and covariance components among health
      disorders and between health disorders, and test-day production traits were from
      bivariate repeatability models. Incidences of health disorders increased with
      increasing parity and were substantially higher at the beginning of lactation.
      Only incidences for ectoparasites slightly increased with increasing stage of
      lactation. Heritabilities ranged from 0.00 for ectoparasites to 0.22 for
      interdigital hyperplasia. Heritabilities of remaining health disorders were in a
      narrow range between 0.04 (corpus luteum persistent) and 0.09 (dermatitis
      digitalis). Clustering diseases into categories did not result in higher
      heritabilities. The variance ratio of the permanent environmental component was
      higher than the heritability for the same trait, pointing to the conclusion that
      non-genetic factors influence repeated occurrence of health problems during
      lactation. Repeatabilities were relatively high with values up to 0.49 for
      interdigital hyperplasia. Genetic correlations among selected health disorders
      were low and close to zero, disproving the assumption that a cow being
      susceptible for a specific disease is also susceptible for other types of health
      disorders. Antagonistic genetic relationships between test-day protein yield and
      health disorders were found for ovarian cysts (0.57) and clinical mastitis
      (0.29). Remaining genetic correlations between diseases and production traits
      were close to zero. The genetic correlation between clinical mastitis and somatic
      cell score was 0.69. This study revealed reliable genetic parameters for health
      disorders and underlined the possibility of precise health data recording by
      farmers from contract herds that can be used for genetic evaluation of health
      traits.

PMID- 22459860
TI  - Short communication: Principal components and factor analytic models for test-day
      milk yield in Brazilian Holstein cattle.
AB  - A total of 46,089 individual monthly test-day (TD) milk yields (10 test-days),
      from 7,331 complete first lactations of Holstein cattle were analyzed. A standard
      multivariate analysis (MV), reduced rank analyses fitting the first 2, 3, and 4
      genetic principal components (PC2, PC3, PC4), and analyses that fitted a factor
      analytic structure considering 2, 3, and 4 factors (FAS2, FAS3, FAS4), were
      carried out. The models included the random animal genetic effect and fixed
      effects of the contemporary groups (herd-year-month of test-day), age of cow
      (linear and quadratic effects), and days in milk (linear effect). The residual
      covariance matrix was assumed to have full rank. Moreover, 2 random regression
      models were applied. Variance components were estimated by restricted maximum
      likelihood method. The heritability estimates ranged from 0.11 to 0.24. The
      genetic correlation estimates between TD obtained with the PC2 model were higher
      than those obtained with the MV model, especially on adjacent test-days at the
      end of lactation close to unity. The results indicate that for the data
      considered in this study, only 2 principal components are required to summarize
      the bulk of genetic variation among the 10 traits.

PMID- 22459861
TI  - Short communication: A new bovine milk-protein variant: alpha-lactalbumin variant
      D.
AB  - Capillary zone electrophoresis of 1,948 Holstein-Friesian cows suggested the
      presence of an unknown protein variant of alpha-lactalbumin (alpha-LA) in the
      milk of 1 cow. Sequencing genomic DNA of this cow showed a polymorphism in the
      alpha-LA gene (LAA) that appears to be responsible for this protein variant. This
      single nucleotide polymorphism g.600G > T was located in exon 2 of LAA and causes
      the amino acid change 65Gln > His in the alpha-LA protein. This alpha-LA protein
      variant is a new protein variant and should be called alpha-LA protein variant D.
      This amino acid change is not expected to affect protein function. Genomic DNA of
      156 bulls of various dairy cattle breeds was screened to examine the presence of
      the new alpha-LA protein variant D. Single nucleotide polymorphism g.600G > T,
      responsible for alpha-LA protein variant D, was not found in any of the 156
      bulls. However, 10 other polymorphisms in the coding and promoter regions of LAA
      were detected that were used to construct haplotypes.

PMID- 22459862
TI  - Technical note: Prediction of liveweight from linear conformation traits in dairy
      cattle.
AB  - The objectives of this study were to derive phenotypic and genetic prediction
      equations of liveweight from linear conformation traits, and estimate genetic and
      phenotypic parameters for these traits. Data pertained to 2,728 conformation and
      liveweight records of 613 cows in 1,529 lactations. Cows were raised at the
      Scottish Agricultural College research station and had calved between 2002 and
      2010. Fifteen linear conformation traits were considered as predictors. To
      validate phenotypic predictions, the data set was randomly split into independent
      reference and validation subsets. Reference subsets were used to derive
      prediction equations with the use of a mixed model. Comparisons between predicted
      and actual liveweight in the validation subsets indicated that stature, chest
      width, body depth, and angularity could be used to derive phenotypic predictions
      of liveweight. Accuracy of these predictions was better for first-lactation than
      for all-lactation liveweight data. Significant genetic correlations between
      liveweight and the 4 predictor traits ranged from 0.49 to 0.76, and phenotypic
      correlations were 0.33 to 0.56. Estimated genetic (co)variances were used to
      develop prediction equations of animal genetic merit for liveweight from
      routinely calculated genetic evaluations for conformation traits.

PMID- 22459863
TI  - Interaction between Lactococcus lactis and Lactococcus raffinolactis during
      growth in milk: development of a new starter culture.
AB  - Many milk fermentations use mixed cultures of lactic acid bacteria. To select a
      new mixed starter culture, 100 acid-producing bacterial strains were isolated
      from raw cow milk. Of these, 13 strains identified as belonging to the genera
      Lactococcus, Lactobacillus, Leuconostoc, or Weissella (based on phenotypic and
      genotypic tests) were assessed for a symbiotic effect between pairs of isolated
      strains during growth in milk. Among the strains tested, a mixed culture of
      Lactococcus lactis ssp. lactis strain 54 and Lactococcus raffinolactis strain 37
      stimulated greater acid production during fermentation than occurred with pure
      fermentation. This stimulatory effect was not observed in milk supplemented with
      yeast extract or glucose or in constituted medium. Addition of a cell-free
      filtrate from milk fermented by strain 54 increased acid production by strain 37;
      however, the converse effect was not observed. The increased acid production by
      this mixed culture was, therefore, due to stimulation of strain 37 by metabolic
      products of strain 54, suggesting that the interaction between strains 54 and 37
      is commensal. Analysis with a taste-sensing system indicated that fermented milk
      containing the mixed culture was more acidic, had more anionic bitterness, had
      greater aftertastes of anionic bitterness and astringency, and was less salty and
      umami than milk containing the individual cultures. This study identifies a new
      commensal relationship between 2 lactococcal strains that are commonly used for
      making dairy products.

PMID- 22459864
TI  - Dairy cow behavior affects the availability of an automatic milking system.
AB  - Facility design can affect the accessibility of an automatic milking system
      (AMS). In particular, gates and alleys positioned around the AMS may affect cow
      traffic and cow behavior, potentially affecting the duration of time the AMS is
      available for milking. Eighty-four Holstein cows of various parities and days in
      milk were randomly divided between 2 groups, each group having access to its own
      AMS. Cow locations and behaviors in the AMS entrance and exit areas, as well as
      in the adjacent holding area, were recorded continuously for 14 d. Cows receiving
      a "no-milking" decision (i.e., cow is rejected from the milking stall due to a
      recent milking event) took longer to exit the milking stall (18.2+/-1.33 s), and
      were more likely to circle and re-enter the AMS (0.8+/-0.15) compared with cows
      receiving a milking decision (16.2+/-1.09 s; 0.2+/-0.03). Cows exiting the AMS
      hesitated for long periods when another cow was near the exit gate (192.93+/-1.11
      s) or in the general holding area (101.04+/-1.07 s). Cows in late lactation had a
      greater probability of hesitating in the exit alley for long periods (0.55+/
      0.09) compared with cows in early lactation (0.15+/-0.07), regardless of whether
      cows were in the holding area. Primiparous cows were more likely to block other
      cows trying to exit (0.60+/-0.13) compared with multiparous cows (0.29+/-0.09).
      Occasionally, blocking events led to "back-up" events, in which the AMS became
      unavailable for new cow access due to a back up of cows through the exit alley
      into the milking stall. The AMS was empty (not occupied) for 10 and 18% (groups 1
      and 2, respectively) of the day; therefore, it was possible that back-up events
      would simply reduce the amount of time the AMS was empty. The duration of back-up
      events and AMS empty events had a negative relationship in group 1 (r=-0.74), but
      no such relationship was observed in group 2. The differences in time budgets
      between the 2 groups suggest that the effect of back-up events on AMS
      availability may be dependent on group social dynamics.

PMID- 22459865
TI  - Management and characteristics of recycled manure solids used for bedding in
      Midwest freestall dairy herds.
AB  - Interest in using recycled manure solids (RMS) as a bedding material for dairy
      cows has grown in the US Midwest. Cost of common bedding materials has increased
      in recent years and availability has decreased. Information regarding the
      composition of RMS and its use as a bedding material for dairy cows in the
      Midwest is very limited. The objectives of this study were to characterize RMS as
      a bedding material, observe bedding management practices, document methods of
      obtaining RMS, and describe housing facilities. We visited 38 Midwest dairy
      operations bedding freestalls with RMS to collect data. Methods of obtaining RMS
      for bedding included separation of anaerobic digested manure, separation of raw
      manure, and separation of raw manure followed by mechanical drum-composting for
      18 to 24 h. Average bedding moisture of unused RMS was 72.4% with a pH of 9.16.
      Unused samples contained (on a dry basis) 1.4% N, 44.9% C, 32.7C:N ratio, 0.44%
      P, 0.70% K, 76.5% neutral detergent fiber, 9.4% ash, 4.4% nonfiber carbohydrates,
      and 1.1% fat. Moisture was lowest for drum-composted solids before and after use
      as freestall bedding. After use in the stalls, digested solids had lower neutral
      detergent fiber content (70.5%) than drum-composted (75.0%) and separated raw
      (73.1%) solids. Total N content was greater in digested solids (2.0%) than in
      separated raw (1.7%) solids. Total bacterial populations in unused bedding were
      greatest in separated raw manure solids but were similar between digested and
      drum-composted manure solids. Drum-composted manure solids had no coliform
      bacteria before use as freestall bedding. After use as bedding, digested manure
      solids had lower total bacteria counts compared with drum-composted and separated
      raw manure solids, which had similar counts. Used bedding samples of digested
      solids contained fewer environmental streptococci than drum-composted and
      separated raw solids and had reduced Bacillus counts compared with separated raw
      solids. Coliform counts were similar for all 3 bedding sources. Addition of a
      mechanical blower post-separation and use of a shelter for storage were
      associated with reduced fresh-bedding moisture but not associated with bacterial
      counts. This was the first survey of herds using RMS for bedding in the Midwest.
      We learned that RMS was being used successfully as a source of bedding for dairy
      cows. For most farms in the study, somatic cell count was comparable to the
      average in the region and not excessively high.

PMID- 22459866
TI  - Characteristics of dairy calf ranches: morbidity, mortality, antibiotic use
      practices, and biosecurity and biocontainment practices.
AB  - The utilization of farming operations specializing in rearing dairy heifer calves
      has increased since the early 1990s. However, these operations have not been as
      well characterized as US dairy operations with respect to demographic and health
      related measures, particularly during the preweaning period. The objective of
      this study was to characterize morbidity, mortality, antibiotic use, and
      biosecurity and biocontainment practices on operations rearing preweaned heifers
      only or preweaned heifer and bull calves (mixed) in the United States. A cross
      sectional survey was performed using a standardized method that included a
      preletter, initial survey, postcard follow-up, and second survey delivered by
      mail. Additional follow-up contacts were attempted by telephone. Descriptive
      statistics for morbidity, mortality, antibiotic use, and biosecurity and
      biocontainment practices were computed at both the operation and calf levels. The
      overall response rate was 50%. Crude yearly mortality averaged 6.9% at the calf
      level, with the median operation reporting 3.6% mortality. Diarrhea was
      experienced by 18% of calves, with 73% receiving an antibiotic. The median
      operation reported 20% diarrhea morbidity with 83% receiving an antibiotic.
      Respiratory disease was experienced by 9.0% of calves, with 82% receiving an
      antibiotic. The median operation reported 5.3% respiratory morbidity, with 100%
      receiving an antibiotic. Heifer-only and mixed operations did not differ in
      operation median morbidity, mortality, or antibiotic treatment rates. Written
      antibiotic protocols were available on 65% of operations. Medicated milk replacer
      was used by 56% of operations. Passive immunity was routinely measured by 46% of
      operations. Direct contact between calves in housing units was not allowed by 45%
      of operations. Of all farms informed of disease concerns at the source farm, 76%
      changed their daily routine as a result. Almost all operations uniquely
      identified calves and recorded mortality. The heifer-only and mixed operations in
      this study were similar to US dairy operations for key health, antibiotic use,
      and biosecurity and biocontainment metrics. This research provides initial
      estimates of key demographics usable by calf ranches, veterinarians, and other
      professionals serving this segment of the US dairy industry.

PMID- 22459867
TI  - Potential gains in lifetime net merit from genomic testing of cows, heifers, and
      calves on commercial dairy farms.
AB  - The objective of this study was to quantify the gains in genetic potential of
      replacement females that could be achieved by using genomic testing to facilitate
      selection and culling decisions on commercial dairy farms. Data were simulated
      for 100 commercial dairy herds, each with 1,850 cows, heifers, and calves.
      Parameters of the simulation were based on the US Holstein population, and
      assumed reliabilities of traditional and genomic predictions matched
      reliabilities of animals that have been genotyped to date. Selection of the top
      10, 20, 30, ..., 90% of animals within each age group was based on parent
      averages and predicted transmitting abilities with or without genomic testing of
      all animals or subsets of animals that had been presorted by traditional
      predictions. Average gains in lifetime net merit breeding value of selected
      females due to genomic testing, minus prorated costs of genotyping the animals
      and their unselected contemporaries, ranged from $28 (top 90% selected) to $259
      (top 20% selected) for heifer calves with no pedigrees, $14 (top 90% selected) to
      $121 (top 10% selected) for heifer calves with known sires, and $7 (top 90%
      selected) to $87 (top 20% selected) for heifer calves with full pedigrees. In
      most cases, gains in genetic merit of selected heifer calves far exceeded
      prorated genotyping costs, and gains were greater for animals with missing or
      incomplete pedigree information. Gains in genetic merit due to genomic testing
      were smaller for lactating cows that had phenotypic records, and in many cases,
      these gains barely exceeded or failed to exceed genotyping costs. Strategies
      based on selective genotyping of the top, middle, or bottom 50% of animals after
      presorting by traditional parent averages or predicted transmitting abilities
      were cost effective, particularly when pedigrees or phenotypes were available and
      a relatively small proportion of animals were to be selected or culled. Based on
      these results, it appears that routine genotyping of heifer calves or yearling
      heifers can be a cost-effective strategy for enhancing the genetic level of
      replacement females on commercial dairy farms. Increasing the accuracy of
      predicted breeding values for young females with genomic testing might lead to
      synergies with other management tools and strategies, such as propagating
      genetically superior females using advanced reproductive technologies or selling
      excess females that were generated by the use of sex-enhanced semen.

PMID- 22459868
TI  - Syncope or seizure? The diagnostic value of synchronous tilt testing and video
      EEG monitoring in children with transient loss of consciousness.
AB  - Syncope and seizure are frequently encountered problems in daily neurology
      practice, and they also share common findings such as transient loss of
      consciousness and atonia. Sometimes, it is difficult to make a differentiation
      between the two entities using only clinical findings. In this study, nineteen
      patients aged between 5 and 20 years who had recurrent transient loss of
      consciousness and occasional atonic events were examined with synchronous tilt
      testing and video-EEG recordings. Eleven patients were initially diagnosed with
      epilepsy, and they were given antiepileptic drugs. Eight patients displayed
      neurally mediated syncope during examination. Four of the eight patients had
      cardioinhibitory syncope type 2B. Three-fourths of the patients with syncope had
      been initially diagnosed with epilepsy and were prescribed antiepileptic drugs.
      One patient with cardioinhibitory syncope who had prolonged asystole and frequent
      attacks needed a cardiac pacemaker. Following implantation, she had no new
      attacks. Synchronous tilt testing and video-EEG recordings give more information
      than doing them separately, and they are helpful in the differential diagnosis of
      syncope and seizure.

PMID- 22459869
TI  - Proposition: limbic encephalitis may represent limbic status epilepticus. A
      review of clinical and EEG characteristics.
AB  - Limbic encephalitis (LE) with waxing and waning neuropsychiatric manifestations
      including behavioral, personality, psychiatric, and memory changes can evolve
      over days to months. Many features of LE show remarkable overlap with the
      characteristics of mesial-temporal (limbic) status epilepticus (MTLSE or LSE).
      With LE, these prolonged impaired states are assumed not to be due to ongoing
      epileptic activity or MTLSE, because scalp EEGs usually show no epileptiform
      spike-wave activity; cycling behavioral and motor changes are attributed to LE;
      there may be little immediate improvement with antiepileptic drugs (AEDs); and of
      course, implanted electrodes are rarely used. Conversely, it is known that in pre
      surgical patients with refractory limbic epilepsy, implanted electrodes have
      revealed limbic seizures that cannot be seen at the scalp. This paper assembles a
      chain of inferences to advance the proposition that refractory LE might represent
      LSE more often than is thought, and that implanted electrodes should be
      considered in some cases. We present two cases that suggest that LE was also LSE,
      one of which warranted implanted electrodes (case 1).

PMID- 22459872
TI  - Increased amplitude of P3 event-related potential in young binge drinkers.
AB  - The aim of the present study was to determine how binge drinking (BD) affects
      brain functioning in male and female university students during the performance
      of a visual discrimination task. Thirty two binge drinkers and 53 controls (non
      binge drinkers), with no history of other drug use, personal or family history of
      alcoholism or psychopathological disorders, were selected. Event-related
      potentials (ERPs) were recorded during the performance of a visual oddball task.
      The latency and amplitude of the N2 and P3b components of the ERPs were analyzed.
      There were no differences between the groups in behavioral measures, but P3b
      amplitudes were significantly larger in binge drinkers than controls. This may
      suggest the presence of anomalies in neural processes mediating attention
      processing, or an imbalance (increased) of neuronal activity in P3b generators
      caused by the presence of BD pattern for a long time.

PMID- 22459870
TI  - Targeting dynorphin/kappa opioid receptor systems to treat alcohol abuse and
      dependence.
AB  - This review represents the focus of a symposium that was presented at the
      "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference
      in Volterra, Italy on May 3-6, 2011 and organized/chaired by Dr. Brendan M.
      Walker. The primary goal of the symposium was to evaluate and disseminate
      contemporary findings regarding the emerging role of kappa-opioid receptors
      (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of
      escalated alcohol consumption, negative affect and cognitive dysfunction
      associated with alcohol dependence, as well as DYN/KOR mediation of the effects
      of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez
      described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr.
      Jay McLaughlin focused on the role of KORs in repeated stress-induced
      potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan
      Walker presented data characterizing the effects of KOR antagonism within the
      extended amygdala on withdrawal-induced escalation of alcohol self-administration
      in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of
      altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that
      could underlie diminished cognitive performance. Collectively, the data presented
      within this symposium identified the multifaceted contribution of KORs to the
      characteristics of acute and chronic alcohol-induced behavioral dysregulation and
      provided a foundation for the development of pharmacotherapeutic strategies to
      treat certain aspects of alcohol use disorders.

PMID- 22459871
TI  - A review of the interactions between alcohol and the endocannabinoid system:
      implications for alcohol dependence and future directions for research.
AB  - Over the past fifty years a significant body of evidence has been compiled
      suggesting an interaction between the endocannabinoid (EC) system and alcohol
      dependence. However, much of this work has been conducted only in the past two
      decades following the elucidation of the molecular constituents of the EC system
      that began with the serendipitous discovery of the cannabinoid 1 receptor (CB1).
      Since then, novel pharmacological and genetic tools have enabled researchers to
      manipulate select components of the EC system, to determine their contribution to
      the motivation to consume ethanol. From these preclinical studies, it is evident
      that CB1 contributes the motivational and reinforcing properties of ethanol, and
      chronic consumption of ethanol alters EC transmitter levels and CB1 expression in
      brain nuclei associated with addiction pathways. These results are augmented by
      in vitro and ex vivo studies showing that acute and chronic treatment with
      ethanol produces physiologically relevant alterations in the function of the EC
      system. This report provides a current and comprehensive review of the literature
      regarding the interactions between ethanol and the EC system. We begin be
      reviewing the studies published prior to the discovery of the EC system that
      compared the behavioral and physiological effects of cannabinoids with ethanol in
      addition to cross-tolerance between these drugs. Next, a brief overview of the
      molecular constituents of the EC system is provided as context for the subsequent
      review of more recent studies examining the interaction of ethanol with the EC
      system. These results are compiled into a summary providing a scheme for the
      known changes to the components of the EC system in different stages of alcohol
      dependence. Finally, future directions for research are discussed.

PMID- 22459873
TI  - Transgenic over expression of nicotinic receptor alpha 5, alpha 3, and beta 4
      subunit genes reduces ethanol intake in mice.
AB  - Abuse of alcohol and smoking are extensively co-morbid. Some studies suggest
      partial commonality of action of alcohol and nicotine mediated through nicotinic
      acetylcholine receptors (nAChRs). We tested mice with transgenic over expression
      of the alpha 5, alpha 3, beta 4 receptor subunit genes, which lie in a cluster on
      human chromosome 15, that were previously shown to have increased nicotine self
      administration, for several responses to ethanol. Transgenic and wild-type mice
      did not differ in sensitivity to several acute behavioral responses to ethanol.
      However, transgenic mice drank less ethanol than wild-type in a two-bottle
      (ethanol vs. water) preference test. These results suggest a complex role for
      this receptor subunit gene cluster in the modulation of ethanol's as well as
      nicotine's effects.

PMID- 22459875
TI  - Fluid filled scleral contact lens in pediatric patients: challenges and outcome.
AB  - PURPOSE: To study the indications and the challenges while fitting scleral
      contact lens (ScCL) filled with fluid prior to lens insertion in pediatric
      patients. METHODS: We retrospectively reviewed charts of patients of 16 years or
      less who received ScCL (PROSE - Prosthetic Replacement of the Ocular Surface
      Ecosystem, Boston Foundation for Sight, Needham Heights, MA, USA) that were
      filled with fluid (Normal saline) before lens insertion during July 2006 to April
      2010. The main goal of ScCL fitting was to improve vision in patients having
      keratoconus (KC) and improve the ocular microenvironment in ocular surface
      disease (OSD). Visual acuity before and after lens wear was noted. RESULTS: Fluid
      filled ScCL were dispensed to 15 patients (20 eyes). The indications for ScCL
      fitting were KC (n = 3 eyes), Stevens Johnson syndrome (SJS, n = 13 eyes),
      radiation keratopathy (n = 1 eye), combined KC and SJS (n = 1 eye) and KC and
      vernal keratoconjunctivitis (VKC, n = 2 eyes). Mean age of the patients was 12.85
      years. The average daily lens wear was 9 h. The vision improved by 2 lines or
      more in 85% and dropped by 2 lines or more in 45% eyes after 4 h of lens wear due
      to tear debris collection. None of the patients had any complications. Patients
      were self sufficient inserting and removing ScCL. Two patients had broken lenses
      during the follow-up. CONCLUSIONS: ScCL are useful for pediatric patients who
      have OSD, irregular astigmatism or the two coexisting; KC combined with VKC or
      SJS, helping to maintain the health of the ocular surface and improves vision in
      these patients.

PMID- 22459876
TI  - 2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis,
      biological activity, structure-activity relationship and mode of action studies.
AB  - 2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious
      protocol. Some of the compounds showed in vitro anti-plasmodial activity against
      drug-sensitive CQ(S) (3D7) and drug-resistant CQ(R) (K1) strains of Plasmodium
      falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2
      nitrophenyl)-2-[(7-chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the
      lowest IC(50) (3.6 nM) value (56-fold less than CQ) against CQ(R) strain.
      Structure-activity profile and binding with heme, MU-oxo-heme have been studied.
      Binding assays with DNA revealed better binding with target parasite type AT rich
      pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic.
      Molecular docking analysis with Pf DHFR allowed identification of stabilizing
      interactions.

PMID- 22459874
TI  - Conceptualizing withdrawal-induced escalation of alcohol self-administration as a
      learned, plasticity-dependent process.
AB  - This article represents one of five contributions focusing on the topic
      "Plasticity and neuroadaptive responses within the extended amygdala in response
      to chronic or excessive alcohol exposure" that were developed by awardees
      participating in the Young Investigator Award Symposium at the "Alcoholism and
      Stress: A Framework for Future Treatment Strategies" conference in Volterra,
      Italy on May 3-6, 2011 that was organized/chaired by Drs. Antonio Noronha and
      Fulton Crews and sponsored by the National Institute on Alcohol Abuse and
      Alcoholism. This review discusses the dependence-induced neuroadaptations in
      affective systems that provide a basis for negative reinforcement learning and
      presents evidence demonstrating that escalated alcohol consumption during
      withdrawal is a learned, plasticity-dependent process. The review concludes by
      identifying changes within extended amygdala dynorphin/kappa-opioid receptor
      systems that could serve as the foundation for the occurrence of negative
      reinforcement processes. While some evidence contained herein may be specific to
      alcohol dependence-related learning and plasticity, much of the information will
      be of relevance to any addictive disorder involving negative reinforcement
      mechanisms. Collectively, the information presented within this review provides a
      framework to assess the negative reinforcing effects of alcohol in a manner that
      distinguishes neuroadaptations produced by chronic alcohol exposure from the
      actual plasticity that is associated with negative reinforcement learning in
      dependent organisms.

PMID- 22459877
TI  - Radiologically placed tunneled hemodialysis catheters: a single pediatric
      institutional experience of 120 patients.
AB  - PURPOSE: To report the outcome of tunneled dialysis catheter insertion in 120
      patients. MATERIALS AND METHODS: A retrospective review of the interventional
      radiology database and electronic medical records of 120 patients who had
      tunneled dialysis catheters inserted from April 1997 to July 2010 was performed
      with institutional review board approval. There were 61 female patients and 59
      male patients, with a mean age of 13.3 years (range, 0.2-28.5 y). A total of 193
      primary insertions and 330 salvage procedures were performed. RESULTS: The
      technical success rate for primary catheter insertions was 100%. Immediate
      complications included self-limiting tract bleeding and air embolism in two of
      193 insertions each (1.03%). Mean indwell duration for primary insertions was 66
      catheter-days (range, 1-765 d), compared with a total mean of 159.4 catheter-days
      (range, 1-1,034 d). Rates of infection and mechanical complications were 0.21 and
      0.9 per 100 total catheter-days, respectively. Mechanical and infections
      complications were increased in children younger than 9 years of age and weighing
      less than 20 kg. The catheter removal rates for infection and mechanical
      complications were 0.084 and 0.081 per 100 catheter-days, respectively. Medical
      salvage procedures, ie, intracatheter thrombolytic agent use or antibiotic
      therapy (52.1%) and interventional radiologic catheter salvage procedures
      (47.1%), increased catheter survival by an average of 54.8 days (range, 0-959 d).
      CONCLUSIONS: Radiologic placement of tunneled hemodialysis catheters is a safe
      and technically successful procedure in pediatric patients. However, there is a
      high rate of infectious and mechanical complications, particularly in younger and
      smaller patients.

PMID- 22459879
TI  - 3T magnetic resonance imaging accurately depicts radiofrequency ablation zones in
      a blood-perfused bovine liver model.
AB  - PURPOSE: To determine if noncontrast T1-weighted (T1W) images from 3T magnetic
      resonance (MR) imaging accurately depict radiofrequency (RF) ablation zones as
      determined macroscopically and microscopically in a blood-perfused bovine liver
      model. MATERIALS AND METHODS: Three-dimensional (3D) gradient-recalled echo (GRE)
      T1W images were obtained on a 3T MR imaging scanner after RF ablations (n = 14)
      of in vitro blood-perfused bovine livers. The resulting central hypointense and
      peripheral hyperintense signal regions were measured and compared with the inner
      tan and outer red zones of the gross specimen. Corresponding ablated hepatic
      tissue samples were examined microscopically and stained with nicotinamide
      adenine dinucleotide phosphate (NADPH) to assess for the presence or absence of
      NADPH diaphorase activity. Bootstrap two-sample hypothesis tests were used to
      compare MR imaging, gross, and histopathologic measurements. RESULTS: The MR
      imaging inner ablation zone had a mean radius of 0.80 cm (range 0.33-1.14 cm);
      the inner zone plus the outer ablation zone had a mean radius of 1.40 cm (range
      1.01-1.74 cm). Comparison of the measurements of the inner ablation zone on MR
      imaging versus the gross specimen showed equivalence (95% confidence interval
      [CI] -0.122 cm, 0.223 cm). Comparison of the measurements of the outer ablation
      zone on MR imaging versus the gross and histologic specimens also showed
      equivalence (95% CI -0.095 cm, 0.244 cm, and -0.146 cm, 0.142 cm). CONCLUSIONS:
      Noncontrast 3D GRE T1W 3T MR imaging accurately depicts the RF ablation zones in
      a blood-perfused bovine liver model and can be used as a noninvasive means to
      assess the 3D morphologic characteristics of RF ablation lesions in the model.

PMID- 22459878
TI  - Simultaneous combined balloon-occluded retrograde transvenous obliteration and
      partial splenic embolization for portosystemic shunts.
AB  - PURPOSE: To evaluate the efficacy and safety of simultaneous combined balloon
      occluded retrograde transvenous obliteration (B-RTO) and partial splenic
      embolization (PSE) for gastric varices and/or hepatic encephalopathy. MATERIALS
      AND METHODS: B-RTO was performed in 19 consecutive patients with gastric varices
      and/or hepatic encephalopathy, of whom 10 received simultaneous combined B-RTO
      and PSE (group 1) and nine received B-RTO monotherapy (group 2). To evaluate the
      safety of these techniques, we analyzed 20 patients who received PSE monotherapy
      during the same period as a control group (group 3). Outcomes were
      retrospectively assessed. RESULTS: No significant differences were observed in
      baseline characteristics among the three groups except for significantly lower
      platelet counts and larger spleen volumes in group 3. In all cases in groups 1
      and 2, gastric varices disappeared and hepatic encephalopathy improved after
      treatment. Procedure times were not significantly different between groups 1 and
      2 (P = .7435). In group 1, the volume of sclerosing agent required for B-RTO was
      significantly lower (P = .0355) and exacerbation of esophageal varices was
      significantly less frequent (P = .0146) than in group 2. Few serious
      complications occurred in patients who received combined therapy. CONCLUSIONS:
      This study indicates that concomitant PSE may help diminish the increase in
      portal venous pressure after B-RTO for portosystemic shunts, and may allow a
      reduction in the volume of hazardous sclerosing agent used. It is worth
      evaluating the efficacy of simultaneous B-RTO and PSE in a prospective study.

PMID- 22459880
TI  - Bartonella infection in urban and rural dogs from the tropics: Brazil, Colombia,
      Sri Lanka and Vietnam.
AB  - Dogs can be infected by a wide range of Bartonella spp., but limited studies have
      been conducted in tropical urban and rural dog populations. We aimed to determine
      Bartonella antibody prevalence in 455 domestic dogs from four tropical countries
      and detect Bartonella DNA in a subset of these dogs. Bartonella antibodies were
      detected in 38 (8.3%) dogs, including 26 (10.1%) from Colombia, nine (7.6%) from
      Brazil, three (5.1%) from Sri Lanka and none from Vietnam. DNA extraction was
      performed for 26 (63%) of the 41 seropositive and 10 seronegative dogs. Four
      seropositive dogs were PCR positive, including two Colombian dogs, infected with
      B. rochalimae and B. vinsonii subsp. berkhoffii, and two Sri Lankan dogs
      harbouring sequences identical to strain HMD described in dogs from Italy and
      Greece. This is the first detection of Bartonella infection in dogs from Colombia
      and Sri Lanka and identification of Bartonella strain HMD from Asia.

PMID- 22459881
TI  - A survey of the traditional food consumption that may contribute to enhanced soil
      ingestion in a Canadian First Nation community.
AB  - Soil ingestion rates in the order of 400 mg d(-1) have been proposed and
      considered plausible for use in human health risk assessments (HHRA) of
      Aboriginal populations and justified by qualitative assessments of the
      traditional subsistence activities that could enhance soil ingestion. The purpose
      of this study was to assess and document the subsistence activities and food
      consumption practiced by a First Nation Community living in a wilderness
      community in Canada to allow for a comparison with the previous qualitative
      assessments of Aboriginal populations and a quantitative mass balance tracer
      element study of the community conducted concurrently. An ethno-cultural survey
      was conducted of the Xeni Gwet'in First Nations community living in the Nemiah
      Valley, approximately 230 km west of Williams Lake, British Columbia. The
      community diet was observed to consist mainly of fish and big game, and was
      supplemented by berries and roots. Outdoor cultural gatherings, hunting and food
      gathering trips and sporting events, with their attendant potential for enhanced
      soil exposure, were observed to be an important facet of community life. The
      survey concluded that a significant portion of the Xeni Gwet'in practise a
      lifestyle similar to the subsistence lifestyles of other indigenous communities,
      where soil exposure scenarios in the order of hundreds of mg d(-1) have been
      proposed.

PMID- 22459882
TI  - A soil ingestion pilot study of a population following a traditional lifestyle
      typical of rural or wilderness areas.
AB  - The relatively few soil ingestion studies underpinning the recommended soil
      ingestion rates for contaminated site human health risk assessments (HHRAs) that
      have been conducted to date assessed soil ingestion in children living in urban
      or suburban areas of the United States, and to a lesser extent, Europe. However,
      the lifestyle of populations living in North American urban and suburban
      environments is expected to involve limited direct contact with soil. Conversely,
      many populations, such as indigenous and Aboriginal peoples residing in rural and
      wilderness areas of North America and worldwide, participate in activities that
      increase the frequency of direct contact with soil. Qualitative exposure of
      Aboriginal populations inhabiting wilderness areas suggest that high levels of
      soil ingestion may occur that are many times greater than those recommended by
      regulatory agencies for use in HHRAs. Accordingly, a study of subjects selected
      from a wilderness community in Canada was conducted using mass balance tracer
      methods to estimate soil ingestion and the results compared with previous soil
      ingestion studies and regulatory guidelines for the soil ingestion rates used in
      HHRA of contaminated sites. A pilot study of 7 subjects living in the Nemiah
      Valley of British Columbia was conducted over a 3-week period. The mean soil
      ingestion rate estimated in this study using the 4 elemental tracers with the
      lowest food-to-soil ratios (i.e., Al, Ce, La, Si), was observed to be
      approximately 75 mg d(-1) (standard deviation 120 mg d(-1)), the median soil
      ingestion rate was 50 mg d(-1), and the 90th percentile was 211 mg d(-1). These
      soil ingestion rate estimates are higher than the soil ingestion estimates
      currently recommended for HHRAs of adults, and higher than those obtained in most
      previous studies of adults. However, the estimates are lower than the earlier
      qualitative assessments of subsistence lifestyles.

PMID- 22459883
TI  - A mine of information: benthic algal communities as biomonitors of metal
      contamination from abandoned tailings.
AB  - Various biomonitoring approaches were tested in the field to assess the response
      of natural periphythic algal communities to chronic metal contamination
      downstream from an abandoned mine tailings site. The accumulation of cadmium
      (Cd), copper (Cu), lead (Pb) and zinc (Zn) as well as the production of
      phytochelatins, the presence of diatom taxa known to tolerate high metal
      concentrations, diatom diversity and the presence of teratologies were
      determined. We observed highly significant relationships between intracellular
      metal and calculated free metal ion concentrations. Such relationships are often
      observed in laboratory studies but have been rarely validated in field studies.
      These results suggest that the concentration of metal inside the field-collected
      periphyton, regardless of its species composition, is a good indicator of
      exposure and is an interesting proxy for bioavailable metal concentrations in
      natural waters. The presence of teratologies and metal-tolerant taxa at our
      contaminated sites provided a clear indication that diatom communities were
      responding to this metal stress. A multi-metric approach integrating various
      bioassessment methods could be used for the field monitoring of metal
      contamination and the quantification of its effects.

PMID- 22459884
TI  - Remediation of a watershed contaminated by heavy metals: a 2-year field
      biomonitoring of periphytic biofilms.
AB  - This study focuses on an industrial contamination site subjected to remediation
      processes since 2007 in the Riou-Mort watershed (southwest France). The purpose
      was to assess the first impacts of remediation on periphytic biofilms, and was
      performed during two years of biomonitoring. Periphytic biofilms were collected
      on glass slides immersed 24 days at different sites along the contamination
      gradient for 12 colonisation cycles. Metal contaminations (Cd and Zn) were
      analysed in biofilms and the evolution of diatom communities was assessed,
      integrating teratology quantifications. Despite remediation work initiated at the
      industrial site, this study demonstrated the persistence of metal contamination
      in water, as well as in biofilms. In addition, our data, showed that the
      remediation process was initially marked by an increase in metal contamination in
      the river, with increasing diatom community shifts. Metal-contaminated biofilms
      presented decreasing species diversities and were dominated by metal-resistant
      species such as Eolimna minima, whom abundances increased in 2010 reaching 57.2+/
      10%. No significant decrease in metal accumulation was observed and total Cd
      content in biofilms collected downstream the industrial site ranged from 772.7+/
      88 in July 2009 to 636.9+/-20 MUg/gDW in July 2010. Results obtained on
      artificial substrates were compared with those of natural substrates and showed
      similar diatom communities and abundances of deformed diatoms but lower
      diversities. This ensured that glass slide subtrates gave a good representation
      of periphytic biofilm health. Finally, results were compared to studies performed
      before the remediation process and this did not reveal a decrease of metal
      accumulation in biofilms nor shifts in taxonomic composition of the communities,
      rather the remaining dominance of metal resistant species such as E. minima was
      confirmed.

PMID- 22459885
TI  - Assessing the impacts of lifetime sun exposure on skin damage and skin aging
      using a non-invasive method.
AB  - BACKGROUND: Ultraviolet radiation exposure during an individuals' lifetime is a
      known risk factor for the development of skin cancer. However, less evidence is
      available on assessing the relationship between lifetime sun exposure and skin
      damage and skin aging. OBJECTIVES: This study aims to assess the relationship
      between lifetime sun exposure and skin damage and skin aging using a non-invasive
      measure of exposure. METHODS: We recruited 180 participants (73 males, 107
      females) aged 18-83 years. Digital imaging of skin hyperpigmentation (skin
      damage) and skin wrinkling (skin aging) on the facial region was measured.
      Lifetime sun exposure (presented as hours) was calculated from the participants'
      age multiplied by the estimated annual time outdoors for each year of life. We
      analyzed the effects of lifetime sun exposure on skin damage and skin aging. We
      adjust for the influence of age, sex, occupation, history of skin cancer, eye
      color, hair color, and skin color. RESULTS: There were non-linear relationships
      between lifetime sun exposure and skin damage and skin aging. Younger
      participant's skin is much more sensitive to sun exposure than those who were
      over 50 years of age. As such, there were negative interactions between lifetime
      sun exposure and age. Age had linear effects on skin damage and skin aging.
      CONCLUSION: The data presented showed that self reported lifetime sun exposure
      was positively associated with skin damage and skin aging, in particular, the
      younger people. Future health promotion for sun exposure needs to pay attention
      to this group for skin cancer prevention messaging.

PMID- 22459886
TI  - Multivariate and geostatistical analyses of the spatial distribution and origin
      of heavy metals in the agricultural soils in Shunyi, Beijing, China.
AB  - An extensive survey was conducted in this study to determine the spatial
      distribution and possible sources of heavy metals in the agricultural soils in
      Shunyi, a representative agricultural suburb in Beijing, China. A total of 412
      surface soil samples were collected at a density of one sample per km(2), and
      concentrations of As, Cd, Cu, Hg, Pb and Zn were analyzed. The mean values of the
      heavy metals were 7.85+/-2.13, 0.136+/-0.061, 22.4+/-6.31, 0.073+/-0.049, 20.4+/
      5.2, and 69.8+/-16.5 mg kg(-1) for As, Cd, Cu, Hg, Pb, and Zn, respectively,
      slightly higher than their background values of Beijing topsoil with the
      exception of Pb, but lower than the guideline values of Chinese Environmental
      Quality Standard for Soils. Multivariate and geostatistical analyses suggested
      that soil contamination of Cd, Cu and Zn was mainly derived from agricultural
      practices. Whereas, As and Pb were due mainly to soil parent materials, and Hg
      was caused by the atmospheric deposits from Beijing City. The identification of
      heavy metal sources in agricultural soils is a basis for undertaking appropriate
      action to protect soil quality.

PMID- 22459888
TI  - Bleeding due to pelvic fractures in female patients: pictorial review of
      multidetector computed tomography imaging.
AB  - Pelvic bone fractures in female patients are a result of high-energy trauma and
      are a significant cause of morbidity and mortality. Their classification is based
      on the mechanism of the traumatic impact force and the evaluation of stability or
      instability of pelvic ring fracture. Vascular hemorrhage is frequently associated
      with pelvic bone disruption and is the main cause of death in polytrauma female
      patients. At many trauma centers, multidetector computed tomography (MDCT) has
      been considered the best modality in the trauma setting as it is also useful in
      characterizing multiple-body traumatic lesions. Specifically, MDCT angiography
      can lead to fast recognition of pelvic vascular injuries to triage patients with
      blunt pelvic trauma and to send those with ongoing arterial hemorrhage to
      appropriate emergent treatment. At contrast medium enhanced MDCT, extravasation
      of contrast material is an accurate finding of active bleeding and enables the
      interventional radiologist to selectively investigate the arteries most likely to
      be involved with prompt angiographic embolization. The potential sites of
      hemorrhage include the pelvic bone, the pelvic venous plexus, the major iliac
      veins, the major iliac arteries, and their peripheral branches. MDCT multiphase
      protocol can accurately differentiate arterial from venous hemorrhage. This
      article discusses the use of multiphase contrast medium enhanced MDCT in
      detecting and characterizing vascular pelvic injuries associated with pelvic
      fractures in trauma female patients.

PMID- 22459889
TI  - Arterial bleeding in pelvic trauma: priorities in angiographic embolization.
AB  - Vascular injuries are a major source of morbidity and mortality in patients with
      blunt pelvic trauma. Up to 40% of patients with pelvic fractures related to blunt
      traumatic injury experience intra-abdominal or intrapelvic bleeding, which is the
      major determining factor of mortality. Sources of hemorrhage within the pelvis
      include injuries to major pelvic arterial and venous structures and vascular
      damage related to osseous fractures. Among patients with pelvic fractures, up to
      20% require emergent transcatheter embolization, depending on the type of injury.
      Angiography is the gold standard for the treatment of pelvic arterial hemorrhage
      associated with pelvic fractures. Transcatheter techniques provide direct
      identification of sources of bleeding. Selective catheterization and flow
      directed particulate emboli can control bleeding from small arteries at sites of
      injury.

PMID- 22459890
TI  - Postpartum hemorrhage: what every radiologist needs to know.
AB  - Postpartum hemorrhage is among the most common causes of maternal morbidity and
      mortality. Postpartum hemorrhage is defined as a blood loss of greater than 500
      mL or any amount that, if not replaced, could cause shock or death in the mother.
      The most common cause of postpartum hemorrhage is uterine atony. This occurs when
      the normal myometrium fails to contract after delivery of the placenta. The
      initial treatment involves the administration of intravenous oxytocin and uterine
      massage. If the initial maneuvers fail to stop the postpartum hemorrhage, other
      techniques, such as uterine packing, suture techniques, uterine or hypogastric
      artery ligation, can be considered. In the last 30 years, a new angiographic
      approach for treatment of postpartum hemorrhage has emerged. Pelvic arterial
      embolization, after emerging as a treatment option to control and prevent
      pregnancy-related hemorrhage, has been established to be safe and effective. The
      goal of treatment for all causes of postpartum hemorrhage is cessation of
      bleeding in a timely fashion, before the onset of consumptive coagulopathy and
      end organ damage.

PMID- 22459893
TI  - Markers of coagulation activation and enhanced fibrinolysis in Gaucher type 1
      patient: Effects of enzyme replacement therapy.

PMID- 22459892
TI  - Finasteride reduces the risk of incident clinical benign prostatic hyperplasia.
AB  - BACKGROUND: Despite the high prevalence of clinical benign prostatic hyperplasia
      (BPH) among older men, there remains a notable absence of studies focused on BPH
      prevention. OBJECTIVE: To determine if finasteride prevents incident clinical BPH
      in healthy older men. DESIGN, SETTING, AND PARTICIPANTS: Data for this study are
      from the Prostate Cancer Prevention Trial. After excluding those with a history
      of BPH diagnosis or treatment, or an International Prostate Symptom Score (IPSS)
      >= 8 at study entry, 9253 men were available for analysis. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: The primary outcome was incident clinical BPH, defined
      as the initiation of medical treatment, surgery, or sustained, clinically
      significant urinary symptoms (IPSS >14). Finasteride efficacy was estimated using
      Cox proportional regression models to generate hazards ratios (HRs). RESULTS AND
      LIMITATIONS: Mean length of follow-up was 5.3 yr. The rate of clinical BPH was 19
      per 1000 person-years in the placebo arm and 11 per 1000 person-years in the
      finasteride arm (p<0.001). In a covariate-adjusted model, finasteride reduced the
      risk of incident clinical BPH by 40% (HR: 0.60; 95% confidence interval, 0.51
      0.69; p<0.001). The effect of finasteride on incident clinical BPH was attenuated
      in men with a body mass index >= 30 kg/m(2) (p(interaction) = 0.04) but otherwise
      did not differ significantly by physical activity, age, race, current diabetes,
      or current smoking. The post hoc nature of the analysis is a potential study
      limitation. CONCLUSIONS: Finasteride substantially reduces the risk of incident
      clinical BPH in healthy older men. These results should be considered in
      formulating recommendations for the use of finasteride to prevent prostate
      diseases in asymptomatic older men.

PMID- 22459894
TI  - Experimental and computational study on molecular structure and vibrational
      analysis of a modified biomolecule: 5-bromo-2'-deoxyuridine.
AB  - In the present study, the experimental and theoretical vibrational spectra of 5
      bromo-2'-deoxyuridine were investigated. The experimental FT-IR (400-4000 cm(-1))
      and MU-Raman spectra (100-4000 cm(-1)) of the molecule in the solid phase were
      recorded. Theoretical vibrational frequencies and geometric parameters (bond
      lengths and bond angles) were calculated using ab initio Hartree Fock (HF) and
      density functional B3LYP method with 6-31G(d), 6-31G(d,p), 6-311++G(d) and 6
      311++G(d,p) basis sets by Gaussian program, for the first time. The assignments
      of vibrational frequencies were performed by potential energy distribution by
      using VEDA 4 program. The optimized geometric parameters and theoretical
      vibrational frequencies are compared with the corresponding experimental data and
      they were seen to be in a good agreement with the each other. Also, the highest
      occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)
      energies were found.

PMID- 22459895
TI  - I'm tired of stress, I prefer fatigue.

PMID- 22459896
TI  - Clinical outcomes of autogenous cancellous bone grafts obtained through the
      portal for tibial nailing.
AB  - BACKGROUND: The purpose of this study is to introduce and review the clinical
      outcomes of a new technique for harvesting autogenous cancellous bone grafts in
      association with tibial intramedullary (IM) nailing. MATERIALS AND METHODS: We
      retrospectively reviewed 21 patients who received autogenous cancellous bone
      grafts obtained from the entry portal of a tibial IM nail for fracture gaps,
      malalignment or nonunion in the lower extremities. All patients were scheduled to
      receive IM nailing or had already received IM nailing for the fixation of an
      ipsilateral tibia shaft fracture. A total of 33 patients who received only tibial
      IM nailing were selected as a control group. Through the follow-up, postoperative
      complications related to the bone harvest were monitored. Further by taking
      serial X-rays, radiographic changes of the donor site and the knee joint were
      closely observed. Knee pain (visual analogue scale (VAS)) and function (Lysholm
      knee score) were compared between the study group and the control group. RESULTS:
      At the last follow-up, the average VAS in the study group was 1.28 (0-5), which
      was not significantly different from the control group (VAS: 1.36, range 0-7)
      (P=0.985). The range of motion of the knee joint was similar in both groups,
      averaging 130.23 degrees  (range: 115-135 degrees ) and 131.36 degrees  (range:
      115-135 degrees ), respectively. There was no significant difference in the
      Lysholm knee score between the study and control groups (P=0.610). All patients
      exhibited complete fracture healing at an average of 6 months and no
      complications associated with the bone donor site were observed. CONCLUSIONS: By
      using the new technique, autogenous cancellous bone grafting can be performed
      conveniently and safely to treat fracture gaps, malalignment or nonunion in the
      lower extremities without additional morbidity at the donor site.

PMID- 22459897
TI  - Predictors of the postoperative range of finger motion for comminuted
      periarticular metacarpal and phalangeal fractures treated with a titanium plate.
AB  - BACKGROUND: Plate and screw fixation was introduced for complex fractures of the
      hand. Several risk factors for a poor functional outcome have been identified,
      but there is a paucity of evidence regarding predictors of finger stiffness in
      difficult hand fractures. The purpose of this prospective cohort study was to
      identify independent prognostic factors of the postoperative total active motion
      (%TAM) in the treatment of metacarpal and phalangeal fractures. METHODS: Seventy
      two patients (62 males, 10 females; 37+/-15 years) with periarticular fractures
      involving metaphyseal comminution and displacement were evaluated at a minimum of
      1 year following surgery. There were 49 phalangeal bone fractures, 30 intra
      articular fractures and 20 associated soft-tissue injuries. The locations of
      plate placement were lateral in 42 patients and dorsal in 30. The mean duration
      from injury to surgery was 7.6 days (range, 0-40 days). There were eight examined
      variables related to patient characteristics (age, gender and hand dominance),
      fracture characteristics (fracture location, joint involvement and associated
      soft-tissue injury) and surgical variables (location of plate placement and
      duration from injury to surgery). Univariate and multivariate linear regression
      analysis were used to identify the degree to which variables affect %TAM at the
      final follow-up. RESULTS: Univariate analysis indicated moderate correlations of
      %TAM with fracture location, associated soft-tissue injury and age. Multiple
      linear regression modelling including fracture location, age and associated soft
      tissue injury resulted in formulae that could account for 46.3% of the
      variability in %TAM: fracture location (beta=-0.388, p<0.001), age (beta=-0.339,
      p<0.001) and associated soft-tissue injury (beta=-0.296, p=0.002). CONCLUSION:
      Phalangeal fracture, increasing age and associated soft-tissue injury were
      important risk factors to identify the postoperative %TAM in the treatment of
      comminuted periarticular metacarpal or phalangeal fracture with a titanium plate.

PMID- 22459898
TI  - p53 in pure epithelioid PEComa: an immunohistochemistry study and gene mutation
      analysis.
AB  - Pure epithelioid PEComa (PEP; so-called epithelioid angiomyolipoma) is rare and
      is more often associated with aggressive behaviors. The pathogenesis of PEP has
      been poorly understood. The authors studied p53 expression and gene mutation in
      PEPs by immunohistochemistry, single-strand conformation polymorphism, and direct
      sequencing in paraffin material from 8 PEPs. A group of classic angiomyolipomas
      (AMLs) were also analyzed for comparison. Five PEPs were from kidneys and 1 each
      from the heart, the liver, and the uterus. PEPs showed much stronger p53 nuclear
      staining (Allred score 6.4 +/- 2.5) than the classic AML (2.3 +/- 2.9) (P < .01).
      There was no p53 single-strand conformation polymorphism identified in either the
      PEPs or the 8 classic AMLs. p53 mutation analyses by direct sequencing of exons 5
      to 9 showed 4 mutations in 3 of 8 PEPs but none in any of the 8 classic AMLs. The
      mutations included 2 missense mutations in a hepatic PEComa and 2 silent
      mutations in 2 renal PEPs. Both the missense mutations in the hepatic PEComa
      involved the exon 5, one involving codon 165, with change from CAG to CAC (coding
      amino acid changed from glutamine to histidine), and the other involving codon
      182, with change from TGC to TAC (coding amino acid changed from cysteine to
      tyrosine). The finding of stronger p53 expression and mutations in epithelioid
      angiomyolipomas might have contributed to their less predictable behavior.
      However, the abnormal p53 expression cannot be entirely explained by p53
      mutations in the exons examined in the PEPs.

PMID- 22459899
TI  - Acinetobacter in modern warfare.
AB  - Increasing appreciation of the role of Acinetobacter baumannii in the aetiology
      of severe nosocomial infections, together with its ability to employ several
      mechanisms to rapidly develop resistance to multiple classes of antimicrobial
      agents, has led to growing interest in this organism over recent years.
      Recognition and subsequent investigation of the significance of pathogenic
      Acinetobacter infections in military personnel sustaining injuries during the
      conflicts in Afghanistan and Iraq has provided an important contribution to the
      epidemiology of infections with Acinetobacter spp. The following review examines
      this recent military experience.

PMID- 22459900
TI  - Exploring the effect of stimulus characteristics on location-based inhibition of
      return using abrupt and ramped stimulus presentation.
AB  - A recent study illustrating the importance of sensory influences on inhibition of
      return (IOR) found stimuli biased towards the parvocellular (P) pathway produced
      greater IOR while stimuli biased towards the magnocellular (M) pathway produced
      less IOR (Brown, 2009; Guenther & Brown, 2007). The present study used a
      different sensory manipulation (temporal onset/offset) to further explore this
      relationship. Greater M activity was expected when stimuli were presented
      abruptly (M-biased) compared to when stimuli were ramped on and off (P-biased).
      Consistent with our recent findings, greater location-based IOR was found under
      ramped vs. abrupt conditions. The results showed location-based IOR is influenced
      by the nature of stimulus presentation (ramped vs. abrupt) providing convergent
      evidence of an IOR mechanism sensitive to M- and P-biased stimuli.

PMID- 22459903
TI  - Liver resection using bipolar InLine multichannel radiofrequency device: impact
      on intra- and peri-operative outcomes.
AB  - AIMS: Liver resection is indicated for several primary and secondary liver
      lesions. We follow up our earlier experience with the use of InLine Multichannel
      Radiofrequency Device (ILMRD, Resect Medical Inc., Fremont, CA) a device that
      produces coagulative necrosis along the transection plane. METHODS: The records
      of 68 consecutive patients who underwent liver resection for primary and
      metastatic liver tumors from August 2000 to December 2008 were reviewed. Data
      analyzed include demographic data as well as complexity of liver resection, intra
      operative blood loss, use of portal triad clamping and transfusion of blood.
      Postoperative outcomes measured were morbidity, hospital and ICU length of stay.
      RESULTS: The median estimated blood loss was 150 mL in the ILMRD group compared
      to 400 mL in the non-ILMRD group (p < 0.0001). Median length of stay was
      decreased in the ILMRD group by a day (7 vs. 8 p < 0.003). There was a
      significant decrease in frequency of parenchymal clamp time (57% vs 84%, p <
      0.001) and median total portal triad clamp time (2.5 vs 30 min p < 0.0001). We
      also noted a significant decrease in the median portal triad clamp time (0 vs 25
      min, p < 0.001) used during the parenchymal transection phase. Furthermore, use
      of the ILMRD device allowed us to perform more complex hepatic resections.
      CONCLUSION: Use of ILMRD to perform radiofrequency-assisted hepatic resection was
      associated with a significant decrease in intra-operative blood loss and earlier
      discharge from the hospital despite increasing complexity of resections and
      decreased use of portal triad clamping.

PMID- 22459902
TI  - External validation of disease-free survival at 2 or 3 years as a surrogate and
      new primary endpoint for patients undergoing radical cystectomy for urothelial
      carcinoma of the bladder.
AB  - PURPOSE: To perform the first external validation of a recently identified
      association between disease-free survival at two years (DFS2) or three years
      (DFS3) and overall survival at five years (OS5) in patients after radical
      cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB).
      METHODS AND METHODS: Records of 2483 patients who underwent RC for UCB at eight
      European centers between 1989 and 2008 were reviewed. The cohort included 1738
      patients with pT2-4a tumors and negative soft tissue surgical margins (STSM)
      according to the selection criteria of the previous study (study group (SG)). In
      addition, 745 patients with positive STSM or other tumor stages (pT0-T1, pT4b)
      that were excluded from the previous study (excluded patient group (EPG)) were
      evaluated. Kappa statistic was used to measure the agreement between DFS2 or DFS3
      and OS5. RESULTS: The overall agreement between DFS2 and OS5 was 86.5% (EPG:
      88.7%) and 90.1% (EPG: 92.1%) between DFS3 and OS5. The kappa values for
      comparison of DFS2 or DFS3 with OS5 were 0.73 (SE: 0.016) and 0.80 (SE: 0.014)
      respectively for the SG, and 0.67 (SE: 0.033) and 0.78 (SE: 0.027) for the EPG
      (all p-values <0.001). CONCLUSIONS: We externally validated a correlation between
      DFS2 or DFS3 and OS5 for patients with pT2-4a UCB with negative STSM that
      underwent RC. Furthermore, this correlation was found in patients with other
      tumor stages regardless of STSM status. These findings indicate DFS2 and DFS3 as
      valid surrogate markers for survival outcome with RC.

PMID- 22459904
TI  - Use of direct thrombin inhibitor for treatment of cerebral venous thrombosis.
AB  - Cerebral venous thrombosis is an uncommon condition with difficulties in
      diagnosis and treatment. There is limited study on the best treatment option for
      this disease. The mainstay of treatment remains systemic anticoagulation with a
      lengthy duration of warfarin, which has a troublesome unpredictable drug effect,
      various drug and food interactions, and an increased risk of bleeding. Recent
      availability of direct thrombin inhibitor provides an alternative option of
      systemic anticoagulation in various thromboembolism conditions. We report 2 cases
      of cerebral venous thrombosis treated with a direct thrombin inhibitor with good
      clinical and radiologic results.

PMID- 22459906
TI  - Formation of the venous thrombus after venous occlusion in the experimental mouse
      model of metabolic syndrome.
AB  - INTRODUCTION: The metabolic syndrome is considered to be a risk factor for the
      venous thromboembolism (VTE) as well as arterial thrombosis. Although obesity,
      hyperglycemia and dyslipidemia are considered to be important triggering factors,
      it is difficult to evaluate the relationship between VTE and the metabolic
      syndrome in a clinical study. Furthermore the mechanism of venous thrombosis
      initiation still remains elusive. MATERIALS AND METHODS: 20 min clamp of superior
      mesenteric vein was applied to 7 w, 16 w-old KK-A(y) mouse and 16 w-old B6J mouse
      (n = 6 in each group), after de-clamp, the view of the mesenteric vein and
      intestinal submucosal venule were observed by the intravital microscopy. RESULTS:
      Massive thrombi formed in the mesenteric vein in 16 w-old KK-A(y) mice, moderate
      thrombi formation was observed in 7 w-old KK-A(y) mice, while very few thrombi
      were observed in B6 J mice. The first event in submucosal venule after de-clamp
      was the adhesion of leukocytes to the endothelium. Subsequently, leukocytes
      assembled and platelets covered the leukocyte cluster. These leukocyte-platelet
      aggregates move from the venule to the vein and finally formed a venous thrombus.
      CONCLUSION: Metabolic syndrome is a risk factor for venous thrombosis. Intravital
      microscopic examination revealed leukocyte and platelet recruitment to the venule
      in the early stages of venous thrombosis formation.

PMID- 22459908
TI  - Physical restraints: abusive and harmful.

PMID- 22459909
TI  - Predicting cause-specific mortality of older men living in the Veterans home by
      handgrip strength and walking speed: a 3-year, prospective cohort study in
      Taiwan.
AB  - OBJECTIVE: To determine prognostic value of handgrip strength (HGS) and walking
      speed (WS) in predicting the cause-specific mortality for older men. DESIGN:
      Prospective cohort study. SETTING: Banciao Veterans Care Home. PARTICIPANTS: 558
      residents aged 75 years and older. MEASUREMENTS: Anthropometric data, lifestyle
      factors, comorbid conditions, biomarkers, HGS, and WS at recruitment; all-cause
      and cause-specific mortality at 3 years after recruitment. RESULTS: During the
      study period, 99 participants died and the baseline HGS and WS were significantly
      lower than survivors (P both <.001). Cox survival analysis showed that subjects
      with slowest quartile of WS were at significantly higher risk of all-cause
      mortality and cardiovascular mortality (hazard ratio [HR] 3.55, 95% confidence
      interval [CI] 1.69-7.43; HR 11.55, 95% CI 2.30-58.04, respectively), whereas the
      lowest quartile of HGS significantly predicted a higher risk of infection-related
      death (HR 5.53, 95% CI 1.09-28.09). Participants in the high-risk status with
      slowest quartile for WS but not those in the high-risk status with weakest
      quartile for HGS had similar high risk of all-cause mortality with the group with
      combined high-risk status (HR 2.96, 95% CI 1.68-5.23; HR 2.58, 95% CI 1.45-4.60,
      respectively) compared with the participants without high-risk status (reference
      group). CONCLUSIONS: Slow WS predicted all-cause and cardiovascular mortality,
      whereas weak HGS predicted a higher risk of infection-related death among
      elderly, institutionalized men in Taiwan. Combining HGS with WS simultaneously
      had no better prognostic value than using WS only in predicting all-cause
      mortality.

PMID- 22459907
TI  - Protease activated receptor-1 (PAR-1) mediated platelet aggregation is dependent
      on clopidogrel response.
AB  - INTRODUCTION: Clopidogrel inhibits ADP mediated platelet aggregation through
      inhibition of the P2Y12 receptor by its active metabolite. Thrombin induces
      platelet aggregation by binding to protease activated receptor-1 (PAR-1), and
      inhibition of PAR-1 has been evaluated in patients treated with clopidogrel to
      reduce ischemic events after acute coronary syndromes. Residual PAR-1 mediated
      platelet aggregation may be dependent on extent of clopidogrel response. MATERIAL
      AND METHODS: Platelet aggregation was measured in 55 patients undergoing elective
      PCI at 16-24 hours after 600 mg clopidogrel loading dose by light transmittance
      aggregometry using ADP 20 MUM and thrombin receptor agonist peptide (TRAP) at 15
      MUM and 25 MUM as agonists. Genomic DNA was genotyped for common CYP2C19
      variants. RESULTS: Increasing quartiles of 20 MUM ADP induced platelet
      aggregation after clopidogrel loading were associated with increasing levels of
      TRAP mediated platelet aggregation. Patients in the highest quartile (clopidogrel
      non-responders) of post treatment ADP aggregation had significantly higher TRAP
      mediated aggregation than the patients in the lowest quartile (clopidogrel
      responders) [TRAP 15 MUM: 79.6 +/- 5% vs. 69.5 +/- 8%, p<0.001]. CONCLUSIONS: Non
      responders to clopidogrel show increased residual platelet aggregation induced by
      TRAP, whereas clopidogrel responders exhibit attenuated response to TRAP.
      Addition of PAR-1 antiplatelet drugs may be most effective in patients with
      reduced clopidogrel response and high residual TRAP mediated platelet
      aggregation.

PMID- 22459901
TI  - Contribution of tumoral and host solute carriers to clinical drug response.
AB  - Members of the solute carrier family of transporters are responsible for the
      cellular uptake of a broad range of endogenous compounds and xenobiotics in
      multiple tissues. Several of these solute carriers are known to be expressed in
      cancer cells or cancer cell lines, and decreased cellular uptake of drugs
      potentially contributes to the development of resistance. As result, the
      expression levels of these proteins in humans have important consequences for an
      individual's susceptibility to certain drug-induced side effects, interactions,
      and treatment efficacy. In this review article, we provide an update of this
      rapidly emerging field, with specific emphasis on the direct contribution of
      solute carriers to anticancer drug uptake in tumors, the role of these carriers
      in regulation of anticancer drug disposition, and recent advances in attempts to
      evaluate these proteins as therapeutic targets.

PMID- 22459910
TI  - Pain--"God's megaphone".

PMID- 22459911
TI  - Using a critical reflection process to create an effective learning community in
      the workplace.
AB  - Learning circles are an enabling process to critically examine and reflect on
      practices with the purpose of promoting individual and organizational growth and
      change. The authors adapted and developed a learning circle strategy to
      facilitate open discourse between registered nurses, clinical leaders, clinical
      facilitators and students, to critically reflect on practice experiences to
      promote a positive learning environment. This paper reports on an analysis of
      field notes taken during a critical reflection process used to create an
      effective learning community in the workplace. A total of 19 learning circles
      were conducted during in-service periods (that is, the time allocated for
      professional education between morning and afternoon shifts) over a 3 month
      period with 56 nurses, 33 students and 1 university-employed clinical supervisor.
      Participation rates ranged from 3 to 12 individuals per discussion. Ten themes
      emerged from content analysis of the clinical learning issues identified through
      the four-step model of critical reflection used in learning circle discussions.
      The four-step model of critical reflection allowed participants to reflect on
      clinical learning issues, and raise them in a safe environment that enabled
      topics to be challenged and explored in a shared and cooperative manner.

PMID- 22459912
TI  - Prognosis of malignant sacrococcygeal germ cell tumours according to their
      natural history and surgical management.
AB  - INTRODUCTION: Malignant sacrococcygeal (SC) germ cell tumours (GCT) may be
      diagnosed as primary pelvic tumour or malignant recurrence of foetal SC teratoma
      (FSCT) operated during the neonatal period. In order to evaluate the difference
      between these two populations, the authors report their experience with SC-GCT
      registered in the French TGM 95 protocol. POPULATION AND METHODS: The protocol
      comprised risk-adapted-chemotherapy (CT) followed by surgery. Standard risk (SR:
      localized tumour completely resected) had no adjuvant therapy. Intermediate-Risk
      (IR: localized tumour, incomplete or no initial surgery with alphaFP<15,000
      ng/ml) received Vinblastine-Bleomycin-Cisplatin regimen; while High-Risk (HR:
      alphaFP > 15,000 ng/ml and/or metastases) received Etoposide-Ifosfamide
      Cisplatin. RESULTS: Fifty-seven patients with SC-GCT, aged 0-80 months (median
      16), were registered between 1995 and 2005. Nineteen patients had secondary SC
      GCT after FSCT. All patients received CT: 17 IR and 1 SR after reevolution; 39 HR
      (25 with metastases). 51 patients underwent delayed surgery, which was incomplete
      in 8 patients. EVOLUTION: Seventy-two percent of the secondary SC-GCT had
      systematic biological follow-up. alphaFP increasing was the first presenting sign
      in 80% of the cases. Patients with secondary SC-GCT had a lower median alphaFP
      level at diagnosis, were less frequently classified as HR and received less CT.
      The two groups with secondary vs. primary SC-GCT had a statistically similar
      favourable outcome (Overall Survival: 93.8% vs. 86.2%; Event-Free Survival: 89.2
      vs. 78.2%; p > 0.34 and >0.32), respectively, but with less burden of therapy.
      CONCLUSIONS: SC-GCT has a good overall prognosis provided complete surgery is
      achieved and CT is administered to IR and HR patients. SC-GCT in patients
      followed by alphaFP after treatment for FSCT had less tumour extension than newly
      diagnosed patients, probably because of earlier detection of the disease.

PMID- 22459913
TI  - A comprehensive study on the relationship between the image quality and imaging
      dose in low-dose cone beam CT.
AB  - While compressed sensing (CS)-based algorithms have been developed for the low
      dose cone beam CT (CBCT) reconstruction, a clear understanding of the
      relationship between the image quality and imaging dose at low-dose levels is
      needed. In this paper, we qualitatively investigate this subject in a
      comprehensive manner with extensive experimental and simulation studies. The
      basic idea is to plot both the image quality and imaging dose together as
      functions of the number of projections and mAs per projection over the whole
      clinically relevant range. On this basis, a clear understanding of the tradeoff
      between the image quality and imaging dose can be achieved and optimal low-dose
      CBCT scan protocols can be developed to maximize the dose reduction while
      minimizing the image quality loss for various imaging tasks in image-guided
      radiation therapy (IGRT). Main findings of this work include (1) under the CS
      based reconstruction framework, image quality has little degradation over a large
      range of dose variation. Image quality degradation becomes evident when the
      imaging dose (approximated with the x-ray tube load) is decreased below 100 total
      mAs. An imaging dose lower than 40 total mAs leads to a dramatic image
      degradation, and thus should be used cautiously. Optimal low-dose CBCT scan
      protocols likely fall in the dose range of 40-100 total mAs, depending on the
      specific IGRT applications. (2) Among different scan protocols at a constant low
      dose level, the super sparse-view reconstruction with the projection number less
      than 50 is the most challenging case, even with strong regularization. Better
      image quality can be acquired with low mAs protocols. (3) The optimal scan
      protocol is the combination of a medium number of projections and a medium level
      of mAs/view. This is more evident when the dose is around 72.8 total mAs or below
      and when the ROI is a low-contrast or high-resolution object. Based on our
      results, the optimal number of projections is around 90 to 120. (4) The
      clinically acceptable lowest imaging dose level is task dependent. In our study,
      72.8 mAs is a safe dose level for visualizing low-contrast objects, while 12.2
      total mAs is sufficient for detecting high-contrast objects of diameter greater
      than 3 mm.

PMID- 22459914
TI  - Prefrontal and limbic resting state brain network functional connectivity differs
      between nicotine-dependent smokers and non-smoking controls.
AB  - BACKGROUND: Brain dysfunction in prefrontal cortex (PFC) and dorsal striatum (DS)
      contributes to habitual drug use. These regions are constituents of brain
      networks thought to be involved in drug addiction. To investigate whether
      networks containing these regions differ between nicotine dependent female
      smokers and age-matched female non-smokers, we employed functional MRI (fMRI) at
      rest. METHODS: Data were processed with independent component analysis (ICA) to
      identify resting state networks (RSNs). We identified a subcortical limbic
      network and three discrete PFC networks: a medial prefrontal cortex (mPFC)
      network and right and left lateralized fronto-parietal networks common to all
      subjects. We then compared these RSNs between smokers and non-smokers using a
      dual regression approach. RESULTS: Smokers had greater coupling versus non
      smokers between left fronto-parietal and mPFC networks. Smokers with the greatest
      mPFC-left fronto-parietal coupling had the most DS smoking cue reactivity as
      measured during an fMRI smoking cue reactivity paradigm. This may be important
      because the DS plays a critical role in maintaining drug-cue associations.
      Furthermore, subcortical limbic network amplitude was greater in smokers.
      CONCLUSIONS: Our results suggest that prefrontal brain networks are more strongly
      coupled in smokers, which could facilitate drug-cue responding. Our data also are
      the first to document greater reward-related network fMRI amplitude in smokers.
      Our findings suggest that resting state PFC network interactions and limbic
      network amplitude can differentiate nicotine-dependent smokers from controls, and
      may serve as biomarkers for nicotine dependence severity and treatment efficacy.

PMID- 22459915
TI  - Individual variability in the locus of prefrontal craving for nicotine:
      implications for brain stimulation studies and treatments.
AB  - BACKGROUND: Attenuation of cue-elicited craving with brain stimulation techniques
      is a growing area of attention in addiction research. This investigation aims to
      guide these studies by assessing individual variability in the location of peak
      cortical activity during cue-elicited craving. METHOD: Twenty-six nicotine
      dependent individuals performed a cue-elicited craving task in a 3T MRI scanner
      while BOLD signal data was collected. The task included epochs of smoking cues,
      neutral cues, and rest. The location of peak activity during smoking cues
      relative to neutral cues ('hot spot') was isolated for each individual. The
      spatial dispersion of the 26 cue-elicited hot spots (1 per participant) was
      quantified via hierarchical clustering. RESULTS: When viewing nicotine cues all
      26 participants had at least one cluster of significant prefrontal cortex
      activity (p<0.05, cluster corrected). Only 62% had peak activity in the medial
      prefrontal cortex cluster (including 100% of the men). In 15% of the participants
      peak activity was located in either the left lateral prefrontal cortex or left
      insula cluster. Peak activity in the remaining 23% was dispersed throughout the
      prefrontal cortex. CONCLUSION: There is considerable individual variability in
      the location of the cue-elicited 'hot spot' as measured by BOLD activity. Men
      appear to have a more uniform location of peak BOLD response to cues than women.
      Consequently, acquiring individual functional imaging data may be advantageous
      for either tailoring treatment to the individual or filtering participants before
      enrollment in treatment.

PMID- 22459916
TI  - ZntR-mediated transcription of zntA responds to nanomolar intracellular free
      zinc.
AB  - In E. coli, ZitB and ZntA are important metal exporters that enhance cell
      viability under high environmental zinc. To understand their functions in
      maintaining zinc homeostasis, we applied a novel genetically-encoded fluorescent
      zinc sensor to monitor the intracellular free zinc changes in wild type, ?zitB
      and ?zntA E. coli cells upon sudden exposure to toxic levels of zinc ("zinc
      shock"). The intracellular readily exchangeable zinc concentration (or "free"
      zinc) increases transiently from picomolar to nanomolar levels, accelerating zinc
      activated gene transcription. After zinc shock, the zitB mRNA level is constant
      while the zntA mRNA increases substantially in a zinc-dependent manner. In the
      ?zitB E. coli strain the free zinc concentration rises more rapidly after zinc
      shock compared to wild type cells while a prolonged accumulation of free zinc is
      observed in the ?zntA strain. Based on these results, we propose that ZitB
      functions as a constitutive, first-line defense against toxic zinc influx, while
      ZntA is up-regulated to efficiently lower the free zinc concentration.
      Furthermore, the ZntR-mediated transcription of zntA exhibits an apparent K(1/2)
      for zinc activation in the nanomolar range in vivo, significantly higher than the
      femtomolar affinity for zinc binding and transcription activation previously
      measured in vitro. A kinetically-controlled transcription model is sufficient to
      explain the observed regulation of intracellular free zinc concentration by ZntR
      and ZntA after zinc shock.

PMID- 22459917
TI  - Structural characterization of Zn(II)-, Co(II)-, and Mn(II)-loaded forms of the
      argE-encoded N-acetyl-L-ornithine deacetylase from Escherichia coli.
AB  - The Zn, Co, and Mn K-edge extended X-ray absorption fine structure (EXAFS)
      spectra of the N-acetyl-l-ornithine deacetylase (ArgE) from Escherichia coli,
      loaded with one or two equivalents of divalent metal ions (i.e., [Zn(II)_(ArgE)],
      [Zn(II)Zn(II)(ArgE)], [Co(II)_(ArgE)], [Co(II)Co(II)(ArgE)], [Mn(II)_(ArgE)], and
      [Mn(II)Mn(II)(ArgE)]), were recorded. The Fourier transformed data (FT) for
      [Zn(II)_(ArgE)], [Zn(II)Zn(II)(ArgE)], [Co(II)_(ArgE)] and [Co(II)Co(II)(ArgE)]
      are dominated by a peak at 2.05A, that can be fit assuming five or six light atom
      (N,O) scatterers. Inclusion of multiple-scattering contributions from the outer
      shell atoms of a histidine-imidazole ring resulted in reasonable Debye-Waller
      factors for these contributions and a slight reduction in the goodness-of-fit
      value (f'). Furthermore, the data best fit a model that included a M-M vector at
      3.3 and 3.4A for Zn(II) and Co(II), respectively, suggesting the formation of a
      dinuclear site. Multiple scattering contributions from the outer-shell atoms of a
      histidine-imidazole rings are observed at ~3 and 4A for Zn(II)- and Co(II)-loaded
      ArgE suggesting at least one histidine ligand at each metal binding site.
      Likewise, EXAFS data for Mn(II)-loaded ArgE are dominated by a peak at 2.19A that
      was best fit assuming six light atom (N,O) scatterers. Due to poor signal to
      noise ratios for the Mn EXAFS spectra, no Mn-Mn vector could be modeled. Peak
      intensities for [M(II)_(ArgE)] vs. [M(II)M(II)(ArgE)] suggest the Zn(II), Co(II),
      and Mn(II) bind to ArgE in a cooperative manner. Since no structural data has
      been reported for any ArgE enzyme, the EXAFS data reported herein represent the
      first structural glimpse for ArgE enzymes. These data also provide a structural
      foundation for the future design of small molecules that function as inhibitors
      of ArgE and may potentially function as a new class of antibiotics.

PMID- 22459918
TI  - Detailed analysis of a randomized, multicenter, comparative trial of dienogest
      versus leuprolide acetate in endometriosis.
AB  - OBJECTIVE: To analyze the secondary efficacy and safety outcomes from a recent
      trial comparing dienogest (DNG) with leuprolide acetate (LA) in women with
      endometriosis. METHODS: A 24-week, open-label, randomized, multicenter study of
      DNG versus LA in women with endometriosis-related pain was assessed for outcomes
      such as responder rates (using predefined thresholds of pain relief), changes in
      single symptoms/signs and sum scores from the Biberoglu and Behrman (B&B) scale,
      clinical laboratory parameters, and measures of quality of life. RESULTS:
      Dienogest was non-inferior to LA for treatment response using all predefined
      thresholds of pain relief and provided equivalent improvements in B&B symptoms
      and signs. No clinically relevant changes in laboratory parameters were observed
      during DNG treatment, whereas estrogen levels decreased in the LA group. Compared
      with LA, DNG was associated with pronounced improvements in specific quality-of
      life measures. CONCLUSION: The analyses provide supportive evidence that the
      efficacy of DNG is equivalent to that of LA for treating endometriosis symptoms,
      with specific quality-of-life benefits and a favorable safety profile.

PMID- 22459919
TI  - Effects of parity and mode of delivery on urinary incontinence among
      postmenopausal women in Taiwan.
AB  - OBJECTIVE: To investigate the association between the prevalence of urinary
      incontinence and parity or mode of delivery among Taiwanese women aged 60 years
      or older. METHODS: Between July 1999 and December 2000, a nationwide
      epidemiologic study was conducted in Taiwan among 2410 women selected by a
      multistage random sampling method. Face-to-face interviews with 1517 women were
      conducted. The relationship between the prevalence of urinary incontinence and
      the number of vaginal deliveries or number of cesarean deliveries was assessed by
      frequency and Pearson chi(2) test using a significance level of less than 0.05.
      Logistic regression was used to investigate the significance of dichotomous
      dependent variables. RESULTS: Decades ago, most Taiwanese women (1435 of 1511
      respondents, 94.97%,) gave birth via vaginal delivery and the rate of cesarean
      delivery was low (20 of 1513 respondents, 1.32%). Parity (odds ratio [OR], 2.42;
      95% confidence interval [CI], 0.87-6.71; P=0.091), vaginal delivery (OR, 0.76;
      95% CI, 0.39-1.47; P=0.408), and cesarean delivery (OR, 1.47; 95% CI, 0.59-3.70;
      P=0.409) did not increase the risk of urinary incontinence. CONCLUSION: There was
      no association between urinary incontinence and parity or mode of delivery among
      Taiwanese postmenopausal women decades after their first delivery.

PMID- 22459920
TI  - The association between pelvic girdle pain and urinary incontinence among
      pregnant women in the second trimester.
AB  - OBJECTIVE: To examine the association among pelvic girdle pain (PGP), urinary
      incontinence (UI), and pelvic floor muscle (PFM) function in pregnant women in
      the second trimester. METHODS: Fifty-five pregnant women (29 with PGP and 26
      without) were enrolled. Urinary incontinence was measured via the International
      Consultation on Incontinence Questionnaire-Short Form. Vaginal examination
      assessed PFM contract-relax patterns and muscle strength. RESULTS: Overall, 51
      women (26 with PGP and 25 without) were included in the final analyses. After
      controlling for PFM muscle strength, women with PGP were significantly more
      likely to have UI (P=0.03). After controlling for pain status, having little or
      no PFM contraction was significantly associated with UI (P=0.03). There was no
      association between PGP and PFM weakness. CONCLUSION: There was an association
      between PGP and UI and between UI and PFM weakness among the study participants.
      Lack of PFM weakness in women with PGP during pregnancy may reflect acuity of
      pain or measurement error.

PMID- 22459921
TI  - Heterologous expression and purification of Arabidopsis thaliana VIM1 protein: in
      vitro evidence for its inability to recognize hydroxymethylcytosine, a rare base
      in Arabidopsis DNA.
AB  - The discovery of 5-hydroxymethyl-cytosine (5hmC) in mammalian cells prompted us
      to look for this base in the DNA of Arabidopsis thaliana (thale cress), and to
      ask how well the Arabidopsis Variant in Methylation 1 (VIM1) protein, an
      essential factor in maintaining 5-cytosine methylation (5mC) homeostasis and
      epigenetic silencing in this plant, recognizes this novel base. We found that the
      DNA of Arabidopsis' leaves and flowers contain low levels of 5hmC. We also cloned
      and expressed in Escherichia coli full-length VIM1 protein, the archetypal member
      of the five Arabidopsis VIM gene family. Using in vitro binding assays, we
      observed that full-length VIM1 binds preferentially to hemi-methylated DNA with a
      single modified 5mCpG site; this result is consistent with its known role in
      preserving DNA methylation in vivo following DNA replication. However, when 5hmC
      replaces one or both cytosine residues at a palindromic CpG site, VIM1 binds with
      approximately >=10-fold lower affinity. These results suggest that 5hmC may
      contribute to VIM-mediated passive loss of cytosine methylation in vivo during
      Arabidopsis DNA replication.

PMID- 22459922
TI  - Consumers' and providers' responses to public cost reports, and how to raise the
      likelihood of achieving desired results.
AB  - There is tremendous interest in different approaches to slowing the rise in US
      per capita health spending. One approach is to publicly report on a provider's
      costs--also called efficiency, resource use, or value measures--with the hope
      that consumers will select lower-cost providers and providers will be encouraged
      to decrease spending. In this paper we explain why we believe that many current
      cost-profiling efforts are unlikely to have this intended effect. One of the
      reasons is that many consumers believe that more care is better and that higher
      cost providers are higher-quality providers, so giving them information that some
      providers are lower cost may have the perverse effect of deterring them from
      accessing these providers. We suggest changes that can be made to content and
      design of public cost reports to increase the intended consumer and provider
      response.

PMID- 22459923
TI  - In a California program, quality and utilization reports on reproductive health
      services spurred providers to change.
AB  - The use of performance indicators has the potential to improve service quality
      and avert costs, yet such indicators have typically not been used to assess
      family planning and reproductive health services. An exception is California's
      Family PACT (Planning, Access, Care, and Treatment) Program, a statewide family
      planning and reproductive health services program. Our study assessed whether the
      behavior of providers participating in this program was influenced by performance
      reports that used both quality improvement and utilization management indicators.
      We examined three indicators in each category from 2005 to 2009 and found that
      change occurred in five of six indicators among private providers and in three of
      six indicators among public providers. Chlamydia screening rates in women age
      twenty-five and younger, for example, increased significantly among both private
      and public providers. Despite the challenges enumerated in this article, we
      conclude that the methodology used in the program could serve as a starting point
      for the development of a uniform set of provider-focused reproductive health
      quality and utilization reports that could be instituted by state family planning
      programs, state Medicaid programs and health plans, and other health care
      delivery systems.

PMID- 22459924
TI  - Purification and antioxidant activity of a polysaccharide from bulbs of
      Fritillaria ussuriensis Maxim.
AB  - A water-soluble polysaccharide (FUP-1) was obtained from Fritillaria ussuriensis
      Maxim through warm water extraction, ethanol precipitation, anion-exchange and
      gel-permeation chromatography. Structural analysis of this compound revealed that
      the average molecular weight of FUP-1 was 4.1*10(4)Da, and the major
      monosaccharide component was xylose, followed by glucose and galactose, at low
      levels. In vitro antioxidant assays showed that FUP-1 exhibited strong hydroxyl,
      superoxide anion and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging
      activities. During in vivo antioxidant testing, the administration of FUP-1 could
      largely attenuate the increase in d-gal-induced malondialdehyde (MDA) and renew
      the activities of superoxide dismutase (SOD) in serums as well as glutathione
      peroxidase (GSH-Px) and the total antioxidant capacity (T-AOC) in the livers of d
      gal-treated mice. Overall, the results of the present study indicate that FUP-1
      exerts antioxidant activity not only through its own radical-scavenging activity
      but also by boosting the enzymatic and nonenzymatic antioxidant defense system of
      the host.

PMID- 22459925
TI  - Isolation and structural characterization of a neutral polysaccharide from the
      stems of Dendrobium densiflorum.
AB  - A novel neutral heteropolysaccharide (DDP-1-D) was purified from hot water
      extracts of dried stem of Dendrobium densiflorum by DEAE-52 and Sephacryl S-200
      High-Resolution Chromatography. The heteropolysaccharide had an average molecular
      weight about 9440 Da. It was composed mainly of glucose and mannose in the ratio
      of 3.01:1. Structural features of DDP-1-D were elucidated by a combination of
      chemical and instrumental techniques, including FT-IR, GC-MS, periodate oxidation
      Smith degradation, (1)H and (13)C NMR spectroscopies (including COSY, TOCSY,
      HSQC, and HMBC spectra). The results indicated that DDP-1-D is a mannoglucan and
      has a backbone consisting of (1->4)-linked alpha-D-Glcp, (1->6)-linked alpha-D
      Glcp, (1->2)-linked alpha-D-Manp and (1->4)-linked beta-Manp. This is the first
      study to provide clear evidence for the structure of the polysaccharide in D.
      densiflorum.

PMID- 22459926
TI  - Electrochemical monitoring of indicator-free DNA hybridization by carbon
      nanotubes-chitosan modified disposable graphite sensors.
AB  - Single walled carbon nanotubes (SWCNT)-chitosan (CHIT) modified pencil graphite
      electrodes (PGEs) were developed for monitoring of DNA hybridization. SWCNT
      chitosan modified PGE (CNT-CHIT-PGE), Chitosan modified PGE (CHIT-PGE) and
      unmodified PGE (bare-PGE) were firstly characterized by using scanning electron
      microscopy (SEM), and their electrochemical behaviors were investigated using
      electrochemical impedance spectroscopy (EIS). The concentrations of CHIT, carbon
      nanotube (CNT) and also amino linked DNA probe etc. were respectively optimized
      in order to obtain the better working conditions of CNT-CHIT modified PGE in DNA
      analysis. The sequence selective DNA hybridization related to Hepatitis B virus
      (HBV) was then explored in the case of hybridization between amino linked HBV
      probe and its complementary (target), or noncomplementary (NC), or mismatch (MM)
      sequences, and also hybridization in mixture sample.

PMID- 22459927
TI  - Silica deposition induced by isolated aluminum ions bound on chelate resin as a
      model compound of the surface of microbes.
AB  - To elucidate the mechanism of silica biodeposition in hot spring water, which is
      induced by Al(3+) ions bound to the surface of microbes, a chelate resin (Chelex
      100) was used as a model compound of the surface of microbes. No silicic acid was
      adsorbed on the Na type Chelex 100, whereas silicic acids were significantly
      adsorbed to the Al type Chelex 100. In the Al type Chelex 100, the Al(3+) ions
      were present as 1:1 tridentate complex with iminodiacetate (IDA) group. After
      adsorption of silicic acid to Al type Chelex 100, a IDA-Al-O-Si-(OH)(3) site
      formed. The site acted as a template for the successive adsorption of silicic
      acids to form silica sheets around Al type Chelex 100 particles. In conclusion,
      Al(3+) ions bound to the surface of microbes play a key role as a trigger for the
      biodeposition of silica in hot spring water.

PMID- 22459928
TI  - Respiratory variations of R-wave amplitude in lead II are correlated with stroke
      volume variations evaluated by transesophageal Doppler echocardiography.
AB  - OBJECTIVE: The authors hypothesized that variations in electrocardiographically
      derived R-wave amplitude might be correlated with mechanical ventilation-induced
      variations in stroke volume as determined by transesophageal echocardiography.
      DESIGN: Observational prospective study. SETTING: Single university hospital.
      PARTICIPANTS: Thirty-four patients undergoing coronary artery bypass surgery.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respiratory R-wave variations
      in lead II (DeltaRII) were correlated with aortic velocity time integral
      variations (r = 0.82, p < 0.0001). Respiratory R-wave variations in leads III and
      aVF and pulse pressure variation also were correlated with aortic velocity time
      integral variations (r = 0.49, p = 0.015; r = 0.61, p = 0.0016; and r = 0.72, p <
      0.0001, respectively). R-wave respiratory variations in lead V(5) were not
      correlated with aortic velocity time integral variations. DeltaRII was correlated
      with pulse pressure variation (r = 0.71, p < 0.0001). A DeltaRII cutoff value of
      15% accurately predicted stroke volume variations >15%, with a specificity of
      92%, a sensitivity of 86%, a positive likelihood ratio of 11.1, a negative
      likelihood ratio of 0.15, a positive predictive value of 95%, and a negative
      predictive value of 80%. CONCLUSIONS: DeltaRII is correlated with stroke volume
      variations as determined by transesophageal echocardiography in mechanically
      ventilated patients and can identify the stroke volume variation cutoff of 15%,
      previously determined to be the cutoff for volume responsiveness.

PMID- 22459929
TI  - Magic bullets in cardiac anesthesia and intensive care.
AB  - Even if the first quasi-randomized study in history was published in 1747, there
      is still a need for evidence-based medicine. In the specific field of cardiac
      anesthesia, there are few magic bullets (ie, drugs/techniques/strategies that
      might reduce perioperative mortality), and a recent international consensus
      conference attempted to list them all. In the absence of evidence-based medicine,
      medical decisions are made by eminence, experience, or physiopathologic
      reasoning. Even if increased or decreased mortality could be observed when
      administering almost every drug used in the current clinical context, if
      correctly studied, research is slowed by bureaucracy, which, together with
      ignorance, is indirectly killing thousands of patients per year. Patients should
      be fully aware of the reduced complication rates and the improved outcomes that
      occur in patients involved in randomized "researcher-driven" clinical trials, the
      so-called "Hawthorne effect." In conclusion, physicians have to do their best
      although they sometimes have little information. Their ability must counteract
      the lack of scientific evidences. Caring for critical patients involves making
      decisions based on realistic tradeoffs of clinical benefit and side effects, but
      too often these choices are made on the basis of extrapolations and educated
      guesses.

PMID- 22459930
TI  - CASE 3--2012. Iatrogenic circumflex artery injury during minimally invasive
      mitral valve surgery.

PMID- 22459931
TI  - Fenoldopam and acute renal failure in cardiac surgery: a meta-analysis of
      randomized placebo-controlled trials.
AB  - OBJECTIVE: Because at present no pharmacologic prevention or treatment of acute
      kidney injury seems to be available, the authors updated a meta-analysis to
      investigate the effects of fenoldopam in reducing acute kidney injury in patients
      undergoing cardiac surgery, focusing on randomized placebo-controlled studies
      only. DESIGN: A meta-analysis of randomized, placebo-controlled trials. SETTING:
      Hospitals. PARTICIPANTS: A total of 440 patients from 6 studies were included in
      the analysis. INTERVENTIONS: None. The ability of fenoldopam to reduce acute
      kidney injury in the perioperative period when compared with placebo was
      investigated. MEASUREMENTS AND MAIN RESULTS: Google Scholar and PubMed were
      searched (updated January 1, 2012). Authors and external experts were contacted.
      Pooled estimates showed that fenoldopam consistently and significantly reduced
      the risk of acute kidney injury (odds ratio [OR] = 0.41; 95% confidence interval
      [CI], 0.23-0.74; p = 0.003), with a higher rate of hypotensive episodes and/or
      use of vasopressors (30/109 [27.5%] v 21/112 [18.8%]; OR = 2.09; 95% CI, 0.98
      4.47; p = 0.06) and no effect on renal replacement therapy, survival, and length
      of intensive care unit or hospital stay. CONCLUSIONS: This analysis suggests that
      fenoldopam reduces acute kidney injury in patients undergoing cardiac surgery.
      Because the number of the enrolled patients was small and there was no effect on
      renal replacement therapy or survival, a large, multicenter, and appropriately
      powered trial is needed to confirm these promising results.

PMID- 22459932
TI  - Intraoperative changes in regional wall motion: can postoperative coronary artery
      bypass graft failure be predicted?
AB  - OBJECTIVE: To evaluate the accuracy of new intraoperative regional wall motions
      abnormalities (RWMAs) detected by transesophageal echocardiography (TEE) to
      predict early postoperative coronary artery graft failure. DESIGN: A
      retrospective study. SETTING: A tertiary care university hospital. PATIENTS: Five
      thousand nine hundred ninety-eight patients who underwent coronary artery bypass
      graft (CABG) surgery. INTERVENTIONS: An evaluation of RWMAs recorded with
      intraoperative TEE before and after cardiopulmonary bypass (CPB) in patients who
      had coronary angiography for suspected postoperative myocardial ischemia based on
      electrocardiogram (ECG), CK-MB, troponin T, hemodynamic compromise, low cardiac
      output, and malignant ventricular arrhythmia. Sensitivity, specificity, positive
      and negative predictive values, odds ratio, 95% confidence interval, and chi
      square analysis were used. MEASUREMENTS AND MAIN RESULTS: Thirty-nine patients
      (0.7%) underwent early coronary angiography for the suspicion of early graft
      dysfunction. Of the 32 patients with diagnosed early graft dysfunction, 5
      patients (15.6%) had shown new intraoperative RWMAs as detected by TEE, 21
      patients (65.6%) had no new RWMAs, no report was available in 5 patients (15.6%),
      and 1 examination (3.1%) was excluded because of poor imaging quality. The
      sensitivity of TEE to predict graft failure was 15.6%, the specificity was 57.1%,
      and the positive predictive and negative values were 62.5% and 12.9%,
      respectively. The odds ratio and 95% confidence interval was 0.1190 (0.0099
      1.4257) when TEE was positive compared with coronary angiography. No association
      was found between new RWMAs detected with TEE and graft failure as documented
      with coronary angiography (p = 0.106). CONCLUSIONS: In this retrospective study,
      RWMAs detected with TEE were of limited value to predict early postoperative CABG
      failure.

PMID- 22459933
TI  - The effect of different lung-protective strategies in patients during
      cardiopulmonary bypass: a meta-analysis and semiquantitative review of randomized
      trials.
AB  - OBJECTIVES: A variety of lung-protective techniques, including continuous
      positive airway pressure and vital capacity maneuvers, have been suggested as
      beneficial when applied during cardiopulmonary bypass (CPB). To better define the
      efficacy of these techniques, a systematic review of different ventilation
      strategies during and after CPB was performed. DESIGN: A systematic review and
      meta-analysis according to Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses recommendations. SETTING: Hospitals. PARTICIPANTS: Eight hundred
      fourteen participants of 16 randomized controlled trials. INTERVENTIONS:
      Continuous positive airway pressure (CPAP), low-volume ventilation, or vital
      capacity maneuvers (VCMs) during CPB. MEASUREMENTS AND MAIN RESULTS: The
      methodologic validity of the included trials was scored according to the Oxford
      scale. Included trials had to report on at least 1 of the following parameters:
      oxygenation, oxygenation index, alveolar-arterial oxygen difference, or shunt
      fraction. The average quality of the included trials was as low as 2 on a scale
      from 1 to 5. The use of CPAP or VCM during CPB led to a significant increase in
      oxygenation parameters immediately after weaning from CPB, but this effect was
      not sustainable and did not improve patient outcome. CONCLUSIONS: This meta
      analysis showed that the positive effects of the designated techniques are
      probably short-lived with a questionable impact on the long-term clinical outcome
      of the treated patients. Based on the available data, it might be impossible to
      advise an optimal or best-evidence strategy of lung preservation during CPB.

PMID- 22459934
TI  - Traditional Chinese medicine herbal preparations in restless legs syndrome (RLS)
      treatment: a review and probable first description of RLS in 1529.
AB  - Occidental medicine has a given definition for restless legs syndrome (RLS) and
      knowledge of RLS pathophysiology has led to the development of its therapeutic
      management. RLS has no cure. Many methods have been used for its treatment, among
      which traditional Chinese medicine (TCM) has been considered as a new approach.
      However, description and management of the disease symptoms can be found in
      Chinese ancient medical systems. The first mention of RLS may have been as early
      as the third century BC described as "leg uncomfortable". Nonetheless, the lack
      of a complete description encompassing all four modern cardinal features of RLS
      makes this uncertain. On the other hand, the first description of RLS
      encompassing three of the four major modern criteria occurs in the ancient book
      of Neike Zhaiyao (Internal summary), 1529 AD just about a century and a half
      prior to the description of RLS by Sir Thomas Willis in England. Here, we
      introduce the philosophical concepts of traditional Chinese medicine and the
      description, classification and understanding of RLS symptoms in traditional
      Chinese medicine. We have conducted an in-depth review of the literature
      reporting one part of TCM, Chinese herbal treatment efficacy for RLS, through
      both English and Chinese search engines. Eighty-five studies were included in the
      review and more than 40 formulas (including 176 different ingredients) were found
      in the literature. According to the literature, Chinese herbs have been
      demonstrated to be safe and hold great potential to be an effective treatment
      modality for RLS, but the evidence is limited by the quality of these studies. Of
      the eighty-five studies, only nine were clinical trials with a control group and
      only three of them were randomized. In cases where herbal preparations were
      compared to Western medications for RLS, the herbal preparations appear to be
      superior. However, uncertainty as to whether the diagnosis of RLS was made in
      accord with Western norms and the use of homemade non-validated rating scales
      create uncertainty as to the meaning of these results. High-quality randomized
      and double blinded clinical trials of Chinese herbs in treating RLS will be
      required in the future. This review highlights aspects of Chinese herbal
      treatment important to guide future research and clinical practice. To our
      knowledge, this is the first systematic English review of the role of Chinese
      herbs in the treatment of RLS.

PMID- 22459935
TI  - Oral potentially malignant disorders: precising the definition.

PMID- 22459936
TI  - KRAS and BRAF mutations in sinonasal cancer.
AB  - OBJECTIVES: [corrected] Despite improvements in the field of surgery and
      radiotherapy, the overall prognosis of sinonasal carcinomas is poor, mainly due
      to the difficulty to resect the tumour completely in this anatomically complex
      region. Therefore, there is great need for alternative treatments. Knowledge of
      the KRAS and BRAF mutational status would become clinically important with regard
      to the possible use of anti-EGFR therapies. MATERIAL AND METHODS: DNA was
      extracted from paraffin embedded tumour samples from 57 cases of sinonasal
      squamous cell carcinoma (SNSCC) and from fresh frozen tumour samples from 58
      cases of intestinal-type sinonasal adenocarcinoma (ITAC). Point mutations were
      analysed for KRAS exon 2 (codons 12 and 13) and BRAF (exon 15, V600E) by direct
      sequencing. RESULTS: Neither KRAS nor BRAF showed any mutations in the SNSCC,
      whereas 7/58 (12%) ITAC harboured KRAS mutations and no BRAF mutations. All seven
      cases with KRAS mutation concerned well-differentiated and less aggressive
      (papillary and colonic type) ITAC, all patients being woodworkers and 4/7 tobacco
      smokers. CONCLUSION: Neither of SNSCCs carried mutations in KRAS and BRAF and a
      low frequency of KRAS mutation was found in ITAC. This suggests that KRAS and
      BRAF mutations play a limited role in the development of sinonasal cancer and
      that mutation analysis is not useful as a screening test for sensitivity to anti
      EGFR therapy in sinonasal cancer.

PMID- 22459937
TI  - Synthesis, photophysical and electrochemical properties of a carbazole dimer
      based derivative with benzothiazole units.
AB  - A novel A-pi-D-pi-D-pi-A type compound, containing two benzothiazole rings as
      electron acceptors and two N-ethylcarbazole groups as electron donors, (E)-1,2
      bis(3-(benzothiazol-2-yl)-9-ethylcarbazol-6-yl)ethene (BBECE), was synthesized
      and characterized by elemental analysis, NMR, MS and thermogravimetric analysis.
      Electrochemical property of compound BBECE was studied by cyclic voltammetry
      analysis. The absorption and emission spectra of BBECE was experimentally
      determined in several solvents and simultaneously computed using density
      functional theory (DFT) and time-dependent density functional theory (TDDFT). The
      calculated absorption and emission wavelengths are coincident with the measured
      data. The lowest-lying absorption spectra can be mainly attributed to
      intramolecular charge transfer (ICT), and the fluorescence spectra can be mainly
      described as originating from an excited state with intramolecular charge
      transfer (ICT) character. The molecular orbitals (HOMO and LUMO), the ionization
      potential (IP), the electron affinity (EA) and reorganization energy of compound
      BBECE were also investigated using density functional theory (DFT). The results
      show that compound BBECE exhibited excellent thermal stability and
      electrochemical stability as well as high fluorescence quantum yield, indicating
      its potential applications as an excellent optoelectronic material in optical
      fields.

PMID- 22459938
TI  - Expression of growth differentiation factor 9 (GDF9), ALK5, and claudin-11 in
      adult alpaca testis.
AB  - Growth differentiation factor 9 (GDF9) is an oocyte-derived factor critical for
      folliculogenesis. Recently, in vitro data showed that GDF9 inhibited the
      localization of tight junction (TJ) proteins, suggesting that GDF9 could
      potentially regulate spermatogenesis in vivo, via inhibition of Sertoli cell TJ
      function. The purpose of the present study was to determine the expression and
      localization of GDF9, its receptor, ALK5, and its latent target protein, claudin
      11 (one of TJ proteins) in adult alpaca testis using Western blot and
      immunohistochemistry. Western blotting results demonstrated that GDF9, ALK5 and
      claudin-11 were expressed in the adult alpaca testis. Immunohistochemistry
      revealed that GDF9 was expressed stage-specifically in the cytoplasm of pachytene
      spermatocytes and round spermatids of the adult alpaca seminiferous epithelium.
      Type I receptor, ALK5 was mainly localized in the cytoplasm of round spermatids
      and Leydig cells, and to a lesser extent in the cytoplasm of pachytene
      spermatocytes and Sertoli cells. Its latent target protein, claudin-11, was
      perpendicular or parallel to the basal lamina in the basal part of Sertoli cells.
      These results indicated that GDF9, as a paracrine and autocrine growth factor
      derived from round spermatids and pachytene spermatocytes, is involved in
      regulating spermatogenesis via action on germ cells or somatic cells (i.e. Leydig
      cells, Sertoli cells).

PMID- 22459939
TI  - [Sedation and analgesia in emergency structure. Paediatry: Which sedation and
      analgesia for child tracheal intubation?].

PMID- 22459940
TI  - [Sedation and analgesia in emergency structure. Which sedation and/or analgesia
      for the entrapped patient?].

PMID- 22459941
TI  - [Sedation and analgesia in emergency structure. Which sedation and/or analgesia
      for multiple victims?].

PMID- 22459942
TI  - [Sedation and analgesia in emergency structure. Reactualization 2010 of the
      Conference of Experts of Sfar of 1999].

PMID- 22459943
TI  - [Sedation and analgesia in emergency structure. Paediatry: Which sedation and
      analgesia for the intubated child under mechanical ventilation?].

PMID- 22459944
TI  - [Sedation and analgesia in emergency structure. Which sedation and analgesia for
      the spontaneously breathing patient in emergency units?].

PMID- 22459945
TI  - Role of MMPs in orchestrating inflammatory response in human monocytes via a TREM
      1-PI3K-NF-kappaB pathway.
AB  - The MMPs constitute a family of endopeptidases that can cleavage extracellular
      proteins. They are involved in a number of events; some of these include
      inflammatory processes. One of its targets is the TREM-1, which has emerged as an
      important modulator of innate immune responses in mammals. This transmembrane
      glycoprotein possesses an Ig-like ectodomain readily shed by MMPs to generate
      sTREM-1. Whereas membrane-anchored TREM-1 amplifies inflammatory responses, sTREM
      1 exhibits anti-inflammatory properties. Here we show that sustained cell surface
      expression of TREM-1 in human monocytes, through metalloproteinase inhibition,
      counteracts the well-characterized down-regulation of several proinflammatory
      cytokines during the ET time-frame, also known as M2 or alternative activation.
      In addition to the cytokines profile, other features of the ET phenotype were
      underdeveloped when TREM-1 was stabilized at the cell surface. These events were
      mediated by the signal transducers PI3Ks and Syk. We also show that sTREM-1
      counteracts the proinflammatory response obtained by membrane TREM-1
      stabilization but failed to induce ET on naive human monocytes. As the sustained
      TREM-1 expression at the cell surface suffices to block the progress of a
      refractory state in human monocytes, our data indicate that TREM-1 and MMPs
      orchestrate an "adaptive" form of innate immunity by modulating the human
      monocytes response to endotoxin.

PMID- 22459946
TI  - Notch system in the linkage of innate and adaptive immunity.
AB  - The lung is one of the most immunologically challenged organs and can be affected
      by a number of pathogens, including bacteria, virus, fungi, and parasites. The
      development and chronicity of pulmonary infection are determined by the early
      innate response to the pathogenic stimuli and are regulated at multiple levels.
      Initial studies have indicated that the interaction of Notch and Notch ligands
      plays a critical role during development, and further, the Notch system is an
      important bridge between APCs and T cell communication circuits. APCs are
      essential regulators of the innate immune response. They can respond to PAMPs
      through PRRs, which function in the recognition of pathogenic components and play
      an important role in the innate and adaptive immune response. T cells are
      essential regulators of adaptive immune responses and infectious diseases.
      However, the role of the Notch system in the cross-talk between APC and T cells
      during pulmonary infection is still poorly understood. In the present review, we
      discuss recent findings that explore the mechanisms underlying the role of Notch
      signaling in the linkage of innate and adaptive immunity, including pulmonary
      infection though PPRs and Notch activation.

PMID- 22459947
TI  - BTLA expression contributes to septic morbidity and mortality by inducing innate
      inflammatory cell dysfunction.
AB  - A proper innate inflammatory response is essential for prevention of the systemic
      inflammation associated with sepsis. BTLA is an immune-regulatory receptor
      demonstrated to be expressed not only on adaptive immune populations and have
      potent inhibitory effects on CD4(+) T cells but is also expressed on innate cell
      populations (CD11c(+) and CD11b(+) cells) and has been shown to diminish pathogen
      clearance following bacterial and parasite infection. The role of BTLA in sepsis
      and the mechanisms by which BTLA alters pathogen clearance, however, have not
      been addressed clearly. Here, we show that following acute experimental sepsis
      induction in mice (CLP), the number of infiltrating BTLA- and HVEM (the ligand
      for BTLA)-expressing macrophages, inflammatory monocytes, mature and immature
      DCs, and neutrophils increased in the peritoneum compared with sham surgery,
      suggesting that a high level of HVEM:BTLA interactions occurs between these cells
      at the site of septic insult. Given this, we evaluated BTLA(-/-) mice, 24 h post
      CLP, and observed a marked increase in the degree of activation on these cell
      populations, as well as a reduction in peritoneal bacterial burden and IL-10
      induction, and most importantly, BTLA(-/-) mice exhibited a higher rate of
      survival and protection from organ injury when compared with WT mice. Such
      changes were not restricted to experimental mice, as circulating BTLA+ and HVEM+
      monocytes and HVEM+ granulocytes were increased in septic ICU patients,
      supporting a role for BTLA and/or HVEM as potential, novel diagnostic markers of
      innate immune response/status and as therapeutic targets of sepsis.

PMID- 22459948
TI  - Characterizing the compression-dependent viscoelastic properties of human hepatic
      pathologies using dynamic compression testing.
AB  - Recent advances in elastography have provided several imaging modalities capable
      of quantifying the elasticity of tissue, an intrinsic tissue property. This
      information is useful for determining tumour margins and may also be useful for
      diagnosing specific tumour types. In this study, we used dynamic compression
      testing to quantify the viscoelastic properties of 16 human hepatic primary and
      secondary malignancies and their corresponding background tissue obtained
      following surgical resection. Two additional backgrounds were also tested. An
      analysis of the background tissue showed that F4-graded fibrotic liver tissue was
      significantly stiffer than F0-graded tissue, with a modulus contrast of 4:1.
      Steatotic liver tissue was slightly stiffer than normal liver tissue, but not
      significantly so. The tumour-to-background storage modulus contrast of
      hepatocellular carcinomas, a primary tumour, was approximately 1:1, and the
      contrast decreased with increasing fibrosis grade of the background tissue. Ramp
      testing showed that the background stiffness increased faster than the malignant
      tissue. Conversely, secondary tumours were typically much stiffer than the
      surrounding background, with a tumour-to-background contrast of 10:1 for colon
      metastases and 10:1 for cholangiocarcinomas. Ramp testing showed that colon
      metastases stiffened faster than their corresponding backgrounds. These data have
      provided insights into the mechanical properties of specific tumour types, which
      may prove beneficial as the use of quantitative stiffness imaging increases.

PMID- 22459950
TI  - An enzyme-based DNA preparation method for application to forensic biological
      samples and degraded stains.
AB  - Extraction of DNA from forensic samples typically uses either an organic
      extraction protocol or solid phase extraction (SPE) and these methods generally
      involve numerous sample transfer, wash and centrifugation steps. Although SPE has
      been successfully adapted to the microdevice, it can be problematic because of
      lengthy load times and uneven packing of the solid phase. A closed-tube enzyme
      based DNA preparation method has recently been developed which uses a neutral
      proteinase to lyse cells and degrade proteins and nucleases [14]. Following a 20
      min incubation of the buccal or whole blood sample with this proteinase, DNA is
      polymerase chain reaction (PCR)-ready. This paper describes the optimization and
      quantitation of DNA yield using this method, and application to forensic
      biological samples, including UV- and heat-degraded whole blood samples on cotton
      or blue denim substrates. Results demonstrate that DNA yield can be increased
      from 1.42 (+/-0.21)ng/MUL to 7.78 (+/-1.40)ng/MUL by increasing the quantity of
      enzyme per reaction by 3-fold. Additionally, there is a linear relationship
      between the amount of starting cellular material added and the concentration of
      DNA in the solution, thereby allowing DNA yield estimations to be made. In
      addition, short tandem repeat (STR) profile results obtained using DNA prepared
      with the enzyme method were comparable to those obtained with a conventional SPE
      method, resulting in full STR profiles (16 of 16 loci) from liquid samples
      (buccal swab eluate and whole blood), dried buccal swabs and bloodstains and
      partial profiles from UV or heat-degraded bloodstains on cotton or blue denim
      substrates. Finally, the DNA preparation method is shown to be adaptable to glass
      or poly(methyl methacrylate) (PMMA) microdevices with little impact on STR peak
      height but providing a 20-fold reduction in incubation time (as little as 60 s),
      leading to a >=1 h reduction in DNA preparation time.

PMID- 22459949
TI  - Collaborative genetic mapping of 12 forensic short tandem repeat (STR) loci on
      the human X chromosome.
AB  - A large number of short tandem repeat (STR) markers spanning the entire human X
      chromosome have been described and established for use in forensic genetic
      testing. Due to their particular mode of inheritance, X-STRs often allow easy and
      informative haplotyping in kinship analyses. Moreover, some X-STRs are known to
      be tightly linked so that, in combination, they constitute even more complex
      genetic markers than each STR taken individually. As a consequence, X-STRs have
      proven particularly powerful in solving complex cases of disputed blood
      relatedness. However, valid quantification of the evidence provided by X-STR
      genotypes in the form of likelihood ratios requires that the recombination rates
      between markers are exactly known. In a collaborative family study, we used X-STR
      genotype data from 401 two- and three-generation families to derive valid
      estimates of the recombination rates between 12 forensic markers widely used in
      forensic testing, namely DXS10148, DXS10135, DXS8378 (together constituting
      linkage group I), DXS7132, DXS10079, DXS10074 (linkage group II), DXS10103,
      HPRTB, DXS10101 (linkage group III), DXS10146, DXS10134 and DXS7423 (linkage
      group IV). Our study is the first to simultaneously allow for mutation and
      recombination in the underlying likelihood calculations, thereby obviating the
      bias-prone practice of excluding ambiguous transmission events from further
      consideration. The statistical analysis confirms that linkage groups I and II are
      transmitted independently from one another whereas linkage groups II, III and IV
      are characterised by inter-group recombination fractions that are notably smaller
      than 50%. Evidence was also found for recombination within all four linkage
      groups, with recombination fraction estimates ranging as high as 2% in the case
      of DXS10146 and DXS10134.

PMID- 22459951
TI  - Analysis of the SNPforID 52-plex markers in four Native American populations from
      Venezuela.
AB  - The SNPforID 52-plex single nucleotide polymorphisms (SNPs) were analyzed in four
      native Venezuelan populations: Bari, Pemon, Panare and Warao. None of the
      population-locus combinations showed significant departure from Hardy-Weinberg
      equilibrium. Calculation of forensic and statistical parameters showed lower
      values of genetic diversity in comparison with African and European populations,
      as well as other, admixed populations of neighboring regions of Caribbean,
      Central and South America. Significant levels of divergence were observed between
      the four Native Venezuelan populations as well as with other previously studied
      populations. Analysis of the 52-plex SNP loci with Structure provided an optimum
      number of population clusters of three, corresponding to Africans, Europeans and
      Native Americans. Analysis of admixed populations indicated a range of membership
      proportions for ancestral populations consisting of Native American, African and
      European components. The genetic differences observed in the Native American
      groups suggested by the 52 SNPs typed in our study are in agreement with current
      knowledge of the demographic history of the Americas.

PMID- 22459953
TI  - Prognosis in 41 severely malnourished anorexia nervosa patients.
AB  - BACKGROUND & AIMS: To report the prognosis in 41 anorexia nervosa (AN) patients
      suffering from very severe malnutrition (mean BMI: 10.1 +/- 0.57 kg/m(2)).
      PATIENTS AND METHODS: Compared with 443 less malnourished AN patients, the 41
      patients were older (27.8 +/- 5.4 vs 22.4 +/- 2.1 yrs), their AN was longer (9.6
      +/- 3.4 vs 5.0 +/- 1.5 yrs) and more often of the restrictive subtype (P < 0.05).
      RESULTS: In 27% of the patients, all nutritional marker levels were in normal
      range. All patients received a prudent tube-refeeding: energy was increased from
      12 to 40 kcal/kg/day, protein from 1.0 to 1.5 g/kg/day within 10 days. During
      stay, 1 patient died, 2 others suffered from myocardial infarction, 2 others from
      acute pancreatitis, and 5 from mental confusion. Compared with the other 443 AN
      patients, the 40 remaining patients had worse 6-yr prognosis: 2 died (7% vs
      1.2%), 29% had severe outcome (vs 10%), and only 41% recovered (vs 62%).
      CONCLUSION: In AN patients with BMI < 11 kg/m(2), a prudent tube-refeeding could
      avoid short-term mortality, but long-term prognosis was bad.

PMID- 22459954
TI  - Biogas productivity by co-digesting Taihu blue algae with corn straw as an
      external carbon source.
AB  - A batch anaerobic test was conducted to evaluate the effects of adding high
      carbon content of corn straw to the digestion of Taihu blue algae to attain an
      optimal C/N ratio for higher methane yield. The addition of corn straw in algae
      at a C/N ratio of 20/1 increased methane yield by 61.69% at 325 mL g(-1)VS(-1)
      (compared with 201 mL g(-1) VS(-1) of algae digestion alone), followed by C/N
      ratios of 16/1 and 25/1, all operated at 20 g VSL(-1) and 35  degrees C. The
      results suggest the optimal C/N ratio for co-digestion of algae with corn straw
      is 20/1. The findings could offer options for efficient methane production and
      waste treatment.

PMID- 22459955
TI  - Optimization of supercritical phase and combined supercritical/subcritical
      conversion of lignocellulose for hexose production by using a flow reaction
      system.
AB  - A flow reaction system was utilized to investigate lignocellulose conversion
      using combined supercritical/subcritical conditions for hexose production.
      Initially, investigation of cellulose hydrolysis in supercritical water and
      optimization of reaction parameters were done. Oligosaccharide yields reached
      over 30% at cellulose concentrations of 3-5 gL(-1) and reaction times of 6-10s at
      375  degrees C, and 2.5-4 gL(-1) and 8-10s at 380  degrees C. Temperatures above
      380  degrees C were not appropriate for the supercritical phase in the combined
      process. Subsequently, conversion of lignocellulosic materials under combined
      supercritical/subcritical conditions was studied. Around 30% hexose was produced
      from corn stalks under the optimal parameters for supercritical (380  degrees C,
      23-24 MPa, 9-10s) and subcritical (240  degrees C, 8-9 MPa, 45-50s) phases. Flow
      systems utilizing the combined supercritical/subcritical technology present a
      promising method for lignocellulosic conversion. The results of this study
      provide an important guide for the operational optimization and practical
      application of the proposed system.

PMID- 22459956
TI  - Surfactant-assisted pretreatment and enzymatic hydrolysis of spent mushroom
      compost for the production of sugars.
AB  - Spent mushroom compost (SMC), a byproduct of commercial mushroom cultivation,
      poses serious environmental problems that have hampered the growth of this
      important agro-industry. In an effort to develop new applications for SMC, we
      explored its use as a feedstock for bioethanol production. SMC constitutes
      approximately 30%w/w polysaccharides, 66% of which is glucan. Following dilute
      acid pretreatment and enzymatic hydrolysis, both in the presence of PEG 6000, 97%
      of glucan and 44% of xylan in SMC were converted into the corresponding
      monosaccharides. Incorporation of PEG 6000 reduced the cellulase requirement by
      77%. Zwittergent 3-12 and 3-14 also significantly increased the efficacy of acid
      pretreatment and enzymatic hydrolysis. The use of SMC in bioethanol production
      represents a potential mitigation solution for the critical environmental issues
      associated with the stockpiling of the major byproduct of the mushroom industry.

PMID- 22459957
TI  - Productivity, carbon utilization, and energy content of mass in scalable
      microalgae systems.
AB  - This study was designed to examine carbon utilization within scalable microalgae
      production systems. Neochloris oleoabundans was produced in replicated troughs
      containing BG11 nutrient formulation. Atmospheric CO(2) was supplemented with ~5%
      CO(2) or with NaHCO(3), and the pH of troughs receiving NaHCO(3) was adjusted
      with HCl or H(3)PO(4). Peak biomass concentrations reached 950, 1140, or 850 mg
      L(-1) and biomass productivities of 109, 96, and 74 mg L(-1) day(-1) were
      achieved in the CO(2), NaHCO(3):HCl and NaHCO(3):H(3)PO(4) troughs, respectively.
      The highest productivity is expected in a scaled-up continuous batch process of
      the CO(2) supplemented system, which was projected to yield 8948 L lipids ha(
      1)yr(-1). Carbon utilization in the CO(2), NaHCO(3):HCl and NaHCO(3):H(3)PO(4)
      systems was ~0.5, 15.5, and 12.9%, while the energy content of the combustible
      biomass was 26.7, 13.2, and 15.4 MJ kg(-1), respectively. Techno-economic
      analyses of microalgal production systems should consider efficiencies and cost
      benefit of various carbon sources.

PMID- 22459958
TI  - Acute inhibitory impact of antimicrobials on acetoclastic methanogenic activity.
AB  - The study evaluated the short-term inhibition impact of three antimicrobials,
      sulfamethoxazole, erythromycin and tetracycline, on the methanogenic activity of
      acclimated biomass fed with acetate. Batch reactors were inoculated each with a
      different antimicrobial concentration in the range of 1-1000 mg/L and they were
      operated during 6 days. Organic substrate removal was monitored by both soluble
      COD and acetate measurements, together with daily measurements of biogas and
      methane generation. While acetate was almost fully removed in all experiments,
      methane generation exhibited a significant drop with increasing antimicrobial
      doses. Almost complete methane inhibition was observed for antimicrobial doses
      above 500 mg/L. Together with adverse impact on process kinetics in the early
      phases of the experiments, the final acute impact of antimicrobials was on
      process stoichiometry, preventing complete utilization of acetate removed in
      metabolic reactions. The observed effect was found compatible with uncompetitive
      inhibition, which similarly exerts a binding impact on substrate-enzyme complex.

PMID- 22459959
TI  - Biomethanation potential of macroalgae Ulva spp. and Gracilaria spp. and in co
      digestion with waste activated sludge.
AB  - Biochemical methane potential of four species of Ulva and Gracilaria genus was
      assessed in batch assays at mesophilic temperature. The results indicate a higher
      specific methane production (per volatile solids) for one of the Ulva sp.
      compared with other macroalgae and for tests running with 2.5% of total solids
      (196+/-9 L CH(4) kg(-1)VS). Considering that macroalgae can potentially be a post
      treatment of municipal wastewater for nutrients removal, co-digestion of
      macroalgae with waste activated sludge (WAS) was assessed. The co-digestion of
      macroalgae (15%) with WAS (85%) is feasible at a rate of methane production 26%
      higher than WAS alone without decreasing the overall biodegradability of the
      substrate (42-45% methane yield). The use of anoxic marine sediment as inoculum
      had no positive effect on the methane production in batch assays. The limiting
      step of the overall anaerobic digestion process was the hydrolysis.

PMID- 22459960
TI  - Hydrolysis and acidification of grass silage in leaching bed reactors.
AB  - Hydrolysis and acidification of grass silage (GS) was examined in leaching bed
      reactors (LBRs) under organic loading rates (OLRs) of 0.5, 0.8 and 1.0 kg
      volatile solids (VS)/m(3)/day. The LBRs were run in duplicate over five
      consecutive batch tests (Batch tests 1-5) to examine the effects of pH, leachate
      dilution and addition of inoculum on the process of hydrolysis and acidification.
      The highest GS hydrolysis yields of 52-58%, acidification yields of 57-60% and VS
      removals of 62-66% were obtained in Batch test 4. Increasing OLRs affected the
      hydrolysis yield negatively. In Batch test 4, the reduction of lignocellulosic
      materials was up to 74.4% of hemicellulose, 30.1% of cellulose and 9.3% of lignin
      within 32 days. Cellulase activity can be used as an indicator for the hydrolysis
      process. Methane production from the LBRs only accounted for 10.0-13.8% of the
      biological methane potential of GS.

PMID- 22459961
TI  - "Solvent-free" ultrasound-assisted extraction of lipids from fresh microalgae
      cells: a green, clean and scalable process.
AB  - In order to comply with criteria of green chemistry concepts and sustainability,
      a new procedure has been performed for solvent-free ultrasound-assisted
      extraction (UAE) to extract lipids from fresh Nannochloropsis oculata biomass.
      Through response surface methodology (RSM) parameters affecting the oil recovery
      were optimized. Optimum conditions for oil extraction were estimated as follows:
      (i) 1000 W ultrasonic power, (ii) 30 min extraction time and (iii) biomass dry
      weight content at 5%. Yields were calculated by the total fatty acids methyl
      esters amounts analyzed by GC-FID-MS. The maximum oil recovery was around 0.21%.
      This value was compared with the one obtained with the conventional extraction
      method (Bligh and Dyer). Furthermore, effect of temperature on the yield was also
      investigated. The overall results show an innovative and effective extraction
      method adapted for microalgae oil recovery, without using solvent and with an
      enable scaling up.

PMID- 22459962
TI  - Effective screening of Scenedesmus sp. from environmental microalgae communities
      using optimal sonication conditions predicted by statistical parameters of
      fluorescence-activated cell sorting.
AB  - The effects of the sonication parameters, including the power and time, were
      investigated for the effective isolation of Scenedesmus sp. from environmental
      microalgae communities when using fluorescence-activated cell sorting (FACS). The
      selectivity, defined as the percentage of Scenedesmus sp. successfully isolated
      and grown in microplates, appeared as peaks in contour plots spanned by the
      sonication power and time. For fast screening of the optimal sonication
      conditions, correlations between the selectivity and the statistical parameters
      from the FACS analysis were investigated. A graphical comparison analysis of the
      contour plots showed a pattern similarity of over 82% between the coefficients of
      variation for the side scatter (SSC-CV) and the selectivity. This predictability
      of the optimal sonication conditions enabled a Scenedesmus sp. selectivity of ca.
      2 times using only one-third of the sonication condition sets arbitrarily chosen
      around the peaks of the SSC-CV, thereby saving resources and time for subsequent
      processes.

PMID- 22459963
TI  - Fusarium verticillioides secretome as a source of auxiliary enzymes to enhance
      saccharification of wheat straw.
AB  - Fusarium verticillioides secretes enzymes (secretome), some of which might be
      potentially useful for saccharification of lignocellulosic biomass since
      supplementation of commercial cellulases from Trichoderma reesei with the F.
      verticillioides secretome improved the enzymatic release of glucose, xylose and
      arabinose from wheat straw by 24%, 88% and 68%, respectively. Determination of
      enzymatic activities revealed a broad range of hemicellulases and pectinases
      poorly represented in commercial cocktails. Proteomics approaches identified 57
      proteins potentially involved in lignocellulose breakdown among a total of 166
      secreted proteins. This analysis highlighted the presence of carbohydrate-active
      enzymes (CAZymes) targeting pectin (from glycoside hydrolase families GH5, GH27,
      GH28, GH43, GH51, GH54, GH62, GH88 and GH93, polysaccharide lyase family PL4 and
      carbohydrate esterase family CE8) and hemicelluloses (from glycoside hydrolase
      families GH3, GH10, GH11, GH30, GH39, GH43 and GH67). These data provide a first
      step towards the identification of candidates to supplement T. reesei enzyme
      preparations for lignocellulose hydrolysis.

PMID- 22459964
TI  - Enhancement of nitrogen removal in a novel anammox reactor packed with Fe
      electrode.
AB  - Slow proliferation of anammox bacteria is a major problem limiting the wider
      application of anammox technology in practical wastewater treatment. A novel
      anammox reactor packed with a Fe electrode was developed for enhancing anammox
      consortium activity and accelerating the startup of anammox process. After 125
      days' operation, total nitrogen removal rate achieved 1209.6 mg N/L/d in this
      hybrid reactor (R1), which was significantly higher than that in a control
      anammox reactor without Fe electrode (R2, 973.3 mg N/L/d). Raising the voltage
      applied for the electrode in a given extent (<=0.6 V) enhanced the performance of
      the reactor, while the voltage more than 0.8 V reduced the anammox performance.
      Scanning electron microscope (SEM) observation along with transmission electron
      microscope (TEM) analysis of the sludge taken from the reactors revealed that a
      more compacted microbial community structure was formed in R1. Fluorescence in
      situ hybridization (FISH) together with DNA analysis indicated that anammox
      bacteria were highly enriched with the presence of the Fe electrode.

PMID- 22459965
TI  - Oil production by the marine microalgae Nannochloropsis sp. F&M-M24 and
      Tetraselmis suecica F&M-M33.
AB  - Nannochloropsis sp. F&M-M24 and Tetraselmis suecica F&M-M33 were cultivated
      outdoors in Green Wall Panels under nutrient deficiency to stimulate oil
      synthesis. Under nitrogen deprivation, Nannochloropsis attained average biomass
      and lipid productivities of 9.9 and 6.5 g m(-2) day(-1), respectively. Starved
      Tetraselmis cultures achieved a biomass productivity of about 7.6 g m(-2) day(-1)
      and a lipid productivity of 1.7 g m(-2) day(-1). Lipids represented 39.1% and
      68.5% of non-starved and starved Nannochloropsis biomass, respectively.
      Starvation did not increase lipid content in Tetraselmis biomass. Important
      differences in lipid classes and in fatty acid composition were observed under
      the different cultivation conditions for both microalgae.

PMID- 22459966
TI  - Safety, pharmacokinetics and pharmacodynamics of four-hour intravenous infusions
      of eritoran in healthy Japanese and Caucasian men.
AB  - Eritoran, a synthetic analogue of lipid A, has been shown to bind to TLR4/MD-2
      complex and thereby block the interaction of endotoxins with TLR4. We report here
      the results of a study conducted to assess the single-dose safety and
      tolerability, as well as the pharmacokinetics and pharmacodynamics, of eritoran
      infusion in Japanese and Caucasian healthy adult men. Sixty-four men (aged 20-45
      years; body mass index 18-30 kg/m(2)) were randomized into four groups: 4-mg
      total dose (six Japanese and six Caucasian men); 12-mg total dose (12 Japanese
      and 12 Caucasian men); 28-mg total dose (six Japanese and six Caucasian men); and
      placebo (eight Japanese and eight Caucasian men). Eritoran in single doses up to
      28 mg over 4 h was well tolerated, with no apparent ethnic differences noted.
      Plasma concentrations were slightly higher in Japanese versus Caucasian men;
      these differences were not significant after adjustment for differences in body
      mass (clearance: approximately 1.2 ml/h/kg; volume of distribution at steady
      state: approximately 0.07 l/kg). The ex vivo endotoxin inhibitory activity of
      eritoran was similar in Japanese and Caucasian men. The data do not indicate any
      need for clinical dose adjustment for possible ethnic-based differences in drug
      distribution or metabolism.

PMID- 22459967
TI  - Dihydrochalcone glucosides and antioxidant activity from the roots of Anneslea
      fragrans var. lanceolata.
AB  - Bioassay-guided fractionation of the roots of Anneslea fragrans var. lanceolata
      led to the isolation of four dihydrochalcone glucosides, davidigenin-2'-O-(6"-O
      4"'-hydroxybenzoyl)-beta-glucoside (1), davidigenin-2'-O-(2"-O-4"'
      hydroxybenzoyl)-beta-glucoside (2), davidigenin-2'-O-(3"-O-4"'-hydroxybenzoyl)
      beta-glucoside (3), and davidigenin-2'-O-(6"-O-syringoyl)-beta-glucoside (4), and
      13 known compounds. The structures were identified by means of spectroscopic
      analysis. Davidigenin-2'-O-(6"-O-syringoyl)-beta-glucoside (4), 1-O-3,4-dimethoxy
      5-hydroxyphenyl-6-O-(3,5-di-O-methylgalloyl)-beta-glucopyranoside (5),
      lyoniresinol (10), and syringic acid (13) showed ABTS [2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid)] cation radical scavenging activity, with
      SC(50) values of 52.6 +/- 5.5, 26.0 +/- 0.7, 6.0 +/- 0.2, and 27.5 +/- 0.6 MUg/mL
      in 20 min, respectively. Lyoniresinol (10), isofraxidin (12), and syringic acid
      (13) also showed DPPH [1,1-diphenyl-2-picrylhydrazyl] radical scavenging
      activity, with SC(50) values of 8.4 +/- 1.8, 51.6 +/- 2.2, and 4.3 +/- 0.7 MUg/mL
      in 30 min, respectively.

PMID- 22459968
TI  - Highly selective antiplasmodial naphthylisoquinoline alkaloids from
      Ancistrocladus tectorius.
AB  - Naphthylisoquinoline alkaloids, named ancistectorine A1, N-methylancistectorine
      A1, ancistectorine A2, 5-epi-ancistectorine A2, ancistectorine A3, ancistectorine
      B1, and ancistectorine C1, have been isolated from twigs of the Chinese plant
      Ancistrocladus tectorius. The structural elucidation succeeded by chemical,
      spectroscopic, and chiroptical methods. Three of these compounds exhibited
      excellent, and specific, antiplasmodial activities, comparable with that of the
      as yet most active representative, dioncophylline C. Moreover, the antitumoral
      activities of two of the main alkaloids in this species was tested.

PMID- 22459969
TI  - Functional characterization of four sesquiterpene synthases from Ricinus communis
      (castor bean).
AB  - Genome sequence analysis of Ricinus communis has indicated the presence of at
      least 22 putative terpene synthase (TPS) genes, 13 of which appear to encode
      sesquiterpene synthases (SeTPSs); however, no SeTPS genes have been isolated from
      this plant to date. cDNAs were recovered for six SeTPS candidates, and these were
      subjected to characterization in vivo and in vitro. The RcSeTPS candidates were
      expressed in either Escherichia coli or Saccharomyces cerevisiae strains with
      engineered sesquiterpene biosynthetic pathways, but only two (RcSeTPS1 and
      RcSeTPS7) produced detectable levels of product. In order to check whether the
      engineered microbial hosts were adequately engineered for sesquiterpene
      production, a selection of SeTPS genes was chosen from other plant species and
      demonstrated consistently high sesquiterpene titers. Activity could be
      demonstrated in vitro for two of the RcSeTPS candidates (RcSeTPS5 and RcSeTPS10)
      that were not observed to be functional in our microbial hosts. RcSeTPS1 produced
      two products, (-)-alpha-copaene and (+)-delta-cadinene, while RcSeTPS7 produced a
      single product, (E, E)-alpha-farnesene. Both RcSeTPS5 and RcSeTPS10 produced
      multiple sesquiterpenes.

PMID- 22459970
TI  - Mechanism of H2S removal during landfill stabilization in waste biocover soil, an
      alterative landfill cover.
AB  - Hydrogen sulfide (H(2)S) is one of the primary contributors to odors at
      landfills. The mechanism of waste biocover soil (WBS) for H(2)S removal was
      investigated in simulated landfill systems with the contrast experiment of a
      landfill cover soil (LCS). The H(2)S removal efficiency was higher than 90%
      regardless of the WBS or LCS covers. The input of landfill gas (LFG) could
      stimulate the growth of aerobic heterotrophic bacteria, actinomycete, sulfate
      reducing bacteria (SRB) and sulfur-oxidizing bacteria (SOB) in the WBS cover,
      while that caused a decrease of 1-2 orders of magnitude in the populations of
      actinomycete and fungi in the bottom layer of the LCS cover. As H(2)S inputted,
      the sulfide content in the WBS cover increased and reached the maximum on day 30.
      In the LCS cover, the highest soil sulfide content was exhibited in the bottom
      layer during the whole experiment. After exposure to LFG, the lower pH value and
      higher sulfate content were observed in the top layer of the WBS cover, while
      there was not a significant difference in different layers of the LCS cover. The
      results indicated a more rapid biotransformation between sulfide and sulfate
      occurred in the WBS cover compared to the LCS.

PMID- 22459971
TI  - Synthesis and photocatalytic application of oriented hierarchical ZnO flower-rod
      architectures.
AB  - An oriented hierarchical ZnO flower-rod arrays (FRs) were prepared on indium
      doped tin oxide (ITO) glass using a facile solution-based method assisted with
      ZnO seed layer. And the as-prepared ZnO FRs/ITO was used as a convenient
      photocatalytic device that recycled without centrifugation. The results show that
      ZnO FRs are wurtzite phase with single crystalline grown along the [001]
      direction. The photoluminescence (PL) spectra illustrate that there are more
      oxygen vacancies on the surface of ZnO FRs compared with ZnO nanoparticles (NPs).
      The electrochemical methods using Rhodamine B (RhB) as electrolyte are also
      performed to study on the photodegradation mechanism where RhB is acted as
      photocatalytic substrate. For ZnO FRs, the higher photoinduced currents under UV
      irradiation and current density prove that the recombination of electron-hole
      pairs is restrained with oxygen vacancies, and the lower charge transfer
      resistance suggest that the charges could move quickly through ZnO oriented
      structures. Therefore, the photocatalytic activity is enhanced by ZnO FRs
      compared with ZnO NPs, and RhB degradation efficiency of ZnO FRs photocatalysts
      is nearly 100% by UV irradiation for 1.5h.

PMID- 22459972
TI  - Hierarchical nitrogen doped bismuth niobate architectures: controllable synthesis
      and excellent photocatalytic activity.
AB  - Nitrogen doped bismuth niobate (N-Bi(3)NbO(7)) hierarchical architectures were
      synthesized via a facile two-step hydrothermal process. XRD patterns revealed
      that the defect fluorite-type crystal structure of Bi(3)NbO(7) remained intact
      upon nitrogen doping. Electron microscopy showed the N-Bi(3)NbO(7) architecture
      has a unique peony-like spherical superstructure composed of numerous nanosheets.
      UV-vis spectra indicated that nitrogen doping in the compound results in a red
      shift of the absorption edge from 450nm to 470nm. XPS indicated that [Bi/Nb]N
      bonds were formed by inducing nitrogen to replace a small amount of oxygen in
      Bi(3)NbO(7-x)N(x), which is explained by electronic structure calculations
      including energy band and density of states. Based on observations of
      architectures formation, a possible growth mechanism was proposed to explain the
      transformation of polyhedral-like nanoparticles to peony-like microflowers via an
      Ostwald riping mechanism followed by self-assembly. The N-Bi(3)NbO(7)
      architectures due to the large specific surface area and nitrogen doping
      exhibited higher photocatalytic activities in the decomposition of organic
      pollutant under visible-light irradiation than Bi(3)NbO(7) nanoparticles.
      Furthermore, an enhanced photocatalytic performance was also observed for Ag/N
      Bi(3)NbO(7) architectures, which can be attributed to the synergetic effects
      between noble metal and semiconductor component.

PMID- 22459973
TI  - Facile, template-free synthesis of silver nanodendrites with high catalytic
      activity for the reduction of p-nitrophenol.
AB  - Here we report a facile, surfactant-free and template-free synthesis process of
      highly uniform dendritic silver nanostructures with high catalytic activity for
      the reduction of p-nitrophenol. By controlling the concentration of AgNO(3)
      aqueous solution and the reaction time, various shapes of silver nanodendrites
      (SNDs) could be obtained easily. The effects of different parameters such as
      concentrations of the reagents and reaction time on the morphology and structure
      of as-prepared tree-like nanostructures have also been investigated by X-ray
      diffraction (XRD), field-emission scanning electron microscopy (FESEM) and
      transmission electron microscopy (TEM). Also, the X-ray photoelectron
      spectroscopy (XPS) has been used to identify the oxidation state of SNDs. In
      addition, the catalytic activity of the as-prepared SNDs samples at 200 mM
      AgNO(3) aqueous solution was evaluated by a redox reaction of p-nitrophenol in
      the presence of an excess amount of NaBH(4). It was found that the highly
      symmetrical SNDs with roughly 60-120 nm in stem and branch diameter and 3-12 MUm
      in length obtained after 120 s reaction time do have higher catalytic activity
      than other SNDs prepared at different reaction time, several times stronger
      catalytic activity in the sodium borohydride reduction of p-nitrophenol to p
      aminophenol, compared to some other silver nanoparticles reported in literature.
      The crystallinity provided by X-ray diffraction (XRD) analysis indicates that the
      improvement of the crystallinity is also very crucial for SNDs' catalytic
      activities. The SNDs are very promising catalytic candidates for the reduction of
      p-nitrophenol because of easily simple preparation route and high catalytic
      activity.

PMID- 22459974
TI  - Characterization and treatment of dissolved organic matter from oilfield produced
      waters.
AB  - Dissolved organic matter (DOM) has been studied intensively in streams, lakes and
      oceans due to its role in the global carbon cycle and because it is a precursor
      of carcinogenic disinfection by-products in drinking water; however, relatively
      little research has been conducted on DOM in oilfield produced waters. In this
      study, recovery of DOM from two oilfield produced waters was relatively low
      (~34%), possibly due to the presence of high concentrations of volatile organic
      compounds (VOCs). A van Krevelen diagram of the extracted DOM suggested the
      presence of high concentrations of lipids, lignin, and proteins, but low
      concentrations of condensed hydrocarbons. Most of the compounds in the oilfield
      DOM contained sulfur in their structures. Fourier transform infrared (FTIR)
      spectra indicated the presence of methyl groups, amides, carboxylic acids, and
      aromatic compounds, which is in agreement with results of Fourier transform ion
      cyclotron resonance (FT-ICR) analysis. Qualitatively, DOM in oilfield produced
      waters is similar to that reported in oceans and freshwater, except that it
      contains much more sulfur and is less aromatic. Treatment studies conducted in a
      fluidized bed reactor suggested that volatilization of organics may be a more
      important mechanism of DOM removal than microbial degradation.

PMID- 22459975
TI  - Calorimetric studies and lessons on fires and explosions of a chemical plant
      producing CHP and DCPO.
AB  - Cumene hydroperoxide (CHP) has been used in producing phenol, dicumyl peroxide
      (DCPO) and as an initiator for synthesizing acrylonitrile-butadiene-styrene (ABS)
      resin by copolymerization in Taiwan. Four incidents of fire and explosion induced
      by thermal runaway reactions were occurred in a same plant producing CHP, DCPO
      and bis-(tert-butylperoxy isopropyl) benzene peroxide (BIBP). The fourth fire and
      explosion occurred in the CHP reactor that resulted in a catastrophic damage in
      reaction region and even spread throughout storage area. Descriptions on the
      occurrences of these incidents were assessed by the features of processes,
      reaction schemes and unexpected side reactions. Calorimetric data on
      thermokinetics and pressure were used for explaining the practical consequences
      or which the worst cases encountered in this kind of plant. Acceptable risk
      associated with emergency relief system design is vital for a plant producing
      organic peroxide. These basic data for designing an inherently safer plant can be
      conducted from adiabatic calorimetry. An encouraging deduction has been drawn
      here, these incidents may be avoided by the implementation of API RP 520, API RP
      521, DIERS technology, OSHA 1910.119 and AIChE's CCPS recommended PSM elements.

PMID- 22459976
TI  - Formation of chlorinated by-products during photo-Fenton degradation of
      pyrimethanil under saline conditions. Influence on toxicity and biodegradability.
AB  - This study evaluated the formation of chlorinated transformation products during
      photo-Fenton treatment of pyrimethanil (PYR-20 mg L(-1)) in two water matrices,
      demineralised water (DW) and water containing 5 g L(-1) of NaCl (DW(NaCl)). All
      experiments were carried out in compound parabolic collectors (CPC) at an initial
      Fe(2+) concentration of 5 mg L(-1) and H(2)O(2) concentration of 150-350 mg L(
      1). Dissolved Organic Carbon (DOC), High-Performance Liquid Chromatography with
      Diode-Array Detection (HPLC-DAD), Liquid Chromatography-Time-Of-Flight Mass
      Spectrometry (LC-TOF-MS), toxicity and biodegradability tests were conducted to
      control the photocatalytic treatment. In DW, PYR was completely eliminated after
      11.8 min of illumination and initial DOC was reduced 50% after 79 min of
      illumination with 33 mM of H(2)O(2) consumed. On the other hand, in DW(NaCl)
      water matrix, the same reduction in DOC took 110 min of illumination and H(2)O(2)
      consumption of 39 mM, and total degradation of PYR was observed at 12 min of
      illumination. PYR transformation products (TPs) were identified by LC-TOF-MS. It
      was demonstrated that photo-Fenton in a DW(NaCl) produces some chlorinated TPs in
      addition to the non-chlorinated TPs identified during degradation in the DW. All
      TPs formed were eliminated during photo-Fenton. Additionally, the presence of
      chlorinated TPs does not increase the toxicity of the water, and TPs formed are
      more biodegradable than PYR.

PMID- 22459977
TI  - Dynamics of aluminum leaching from water purification sludge.
AB  - In this investigation, the shrinking core model is used to study the rate of
      aluminum salt leaching from water purification sludge (WPS). This model, which
      describes the aluminum leaching rate, can be developed to maximize the Al(III)
      recovering efficiency. Laboratory results indicate that when the mixing speed
      exceeds 80rpm, the effect of film diffusion control on the leaching process is
      greatly reduced, such that any further increase in the mixing speed does not
      affect the Al(III) leaching rate. Additionally, increasing the temperature or
      acid concentration improves Al(III) leaching rate. The laboratory data were
      verified by using the shrinking core model to confirm that the leaching of
      Al(III) from WPS is consistent with the inert-layer diffusion control model. This
      finding reveals that large amounts of SiO(2), Al(2)O(3) and other inert
      constituents will form an inter diffusion layer in the WPS and thus become the
      major limiting factors that control the Al(III) leaching process. The dynamic
      equation can be expressed as 1-3(1-x)(2/3)+2(1-x)=(2707.3 exp(-3887.6/T))t, in
      which the apparent activation energy and pre-exponential factors are 32.32 kJ/mol
      and 2707.3 min(-1), respectively, as determined by solving the Arrhenius
      equation.

PMID- 22459978
TI  - Effects of municipal sewage sludge stabilized by fly ash on the growth of
      Manilagrass and transfer of heavy metals.
AB  - A greenhouse experiment was carried out to evaluate the feasibility of using an
      artificial soil for cultivation of Manilagrass. The transfer and transformation
      of heavy metals in the artificial soil-Manilagrass system were discussed at the
      same time. The results showed that fly ash-sludge indicated a positive effect on
      the growth of Manilagrass. The pots with 14% sludge and 6% fly ash mixture had
      the highest yield and nutrient concentrations of Manilagrass. With the increasing
      application of coal fly ash, the concentrations of Ni, Zn, Mn, Sb and Cu in
      Manilagrass decreased significantly, while Pb, V and Ti increased. Otherwise, the
      concentrations of Cd, As, Cr, Co, and Fe did not show a remarkable change. Except
      for Sb, the values of bio-concentration factor of heavy metals in Manilagrass
      were all below 1.0 after treated by the fly ash-sludge treatment, decreased as
      Sb>Ni>Zn>Cu>Pb>Mn>Co=Cr>Cd>Fe=V>Ti>As in an average for all treatments. Compared
      to the contrast check, the proportions of heavy metals in exchangeable, reducible
      and oxidizable fractions increased. Manilagrass could be used to reduce the eco
      toxicity and bioavailability of Ti, V, Mn, Co, Cr and Cd in fly ash-sludge
      amended soil.

PMID- 22459979
TI  - Breakthrough analysis for water disinfection using silver nanoparticles coated
      resin beads in fixed-bed column.
AB  - This study demonstrates the use of silver nanoparticles coated resin beads in
      deactivating microbes in drinking water in a column filtration system. The coated
      resin beads are characterized using X-ray diffraction (XRD), Fourier transform
      infra-red (FT-IR), scanning electron microscope (SEM), transmission electron
      microscope (TEM) and energy dispersive spectroscopy (EDS) to confirm the
      functional groups, morphology and the presence of silver nanoparticles on the
      surface of the resin. The performance of the coated resin is evaluated as a
      function of bed mass, initial bacterial concentration and flow rate using
      Escherichia coli as model microbial contaminant in water. The survival curves of
      E. coli are expressed as breakthrough curves (BTCs), which are modeled using
      sigmoidal regression equations to obtain relevant rate parameters. The number of
      bed volumes processed at breakthrough point and capacity of the bed are used as
      performance indicators. Results show that performance increases with a decrease
      in initial bacterial concentration, an increase in flow rate and an increase in
      bed mass.

PMID- 22459980
TI  - Comparative biochemical and RAPD analysis in two varieties of rice (Oryza sativa)
      under arsenic stress by using various biomarkers.
AB  - Multiple biomarker systems have been frequently used to measure the genotoxic
      effects of environmental pollutants (including heavy metals) on living organisms.
      In this study, we used leaves of hydroponically grown 14 days old seedlings of
      rice (Oryza sativa) varieties (PB1 and IR64) treated with 50, 150 and 300 MUM
      arsenite (As(III)) for 24 and 96 h duration. Reduction in seed germination, root
      shoot length, chlorophyll and protein were observed with increasing As(III)
      concentration and duration in both varieties, being more in IR64.
      Increase/decrease of antioxidant enzymes and stress related parameters showed
      much changes at higher concentration for 24 and 96 h duration in both varieties.
      Eleven primers were found in RAPD analysis to produce polymorphic band pattern
      and produced a total of 51 (control), 79 (treated) and 42 (control) and 29
      (treated) bands in PB1 and IR64 varieties, respectively. These results indicated
      that genomic template stability (GTS, changes in RAPD profile) was significantly
      affected at all tested As(III) concentration, when compared with other
      parameters. Differential response was observed in both varieties with PB1 being
      more tolerant. We concluded that DNA polymorphism detected by RAPD analysis in
      conjunction with other biochemical parameters could be a powerful eco
      toxicological tool in bio-monitoring arsenic pollution.

PMID- 22459981
TI  - Inter-professional differences in compliance with standard precautions in
      operating theatres: a multi-site, mixed methods study.
AB  - BACKGROUND: Occupational acquisition of blood-borne infections has been reported
      following exposure to blood or body fluids. Consistent adherence to standard
      precautions will reduce the risk of infection. OBJECTIVES: To identify: the
      frequency of self-reported adverse exposure to blood and body fluids among
      surgeons and scrub nurses during surgical procedures; contributory factors to
      such injuries; the extent of compliance with standard precautions; and factors
      influencing compliance with precautions. DESIGN: A multi-site mixed methods study
      incorporating a cross-sectional survey and interviews. SETTINGS: Six NHS trusts
      in Wales between January 2006 and August 2008. PARTICIPANTS: Surgeons and scrub
      nurses and Senior Infection Control Nurses. METHODS: A postal survey to all
      surgeons and scrub nurses, who engaged in exposure prone procedures, followed by
      face to face interviews with surgeons and scrub nurses, and telephone interviews
      with Infection Control Nurses. RESULTS: Response rate was 51.47% (315/612). Most
      219/315 (69.5%) respondents reported sustaining an inoculation injury in the last
      five years: 183/315 (58.1%) reported sharps' injuries and 40/315 (12.7%)
      splashes. Being a surgeon and believing injuries to be an occupational hazard
      were significantly associated with increased risk of sharps' injuries (adjusted
      odds ratio 1.73, 95% confidence interval 1.04-2.88 and adjusted odds ratio 2.0,
      1.11-3.5, respectively). Compliance was incomplete: 31/315 (10%) respondents
      always complied with all available precautions, 1/315 (0.003%) claimed never to
      comply with any precautions; 64/293 (21.8%) always used safety devices, 141/310
      (45.5%) eye protection, 72 (23.2%) double gloves, and 259/307 (84.4%) avoided
      passing sharps from hand to hand. Others selected precautions according to their
      own assessment of risk. Surgeons were less likely to adopt eye protection
      (adjusted odds ratio 0.28, 0.11-0.71) and to attend training sessions (odds ratio
      0.111, 0.061-0.19). The professions viewed the risks associated with their roles
      differently, with nurses being more willing to follow protocols. CONCLUSION:
      Inter-professional differences in experiencing adverse exposures must be
      addressed to improve safety and reduce infection risks. This requires new
      training initiatives to alter risk perception and promote compliance with
      policies and procedures.

PMID- 22459982
TI  - Maternal mortality.
AB  - PURPOSE OF REVIEW: This review summarizes recent developments in maternal
      mortality surveillance, and draws from recent confidential mortality reports to
      suggest ways the anesthesiologist can contribute to safer systems of care. RECENT
      FINDINGS: Maternal mortality rates appear to be static in much of the developed
      world, but are increasing in the USA. While improvements in ascertainment explain
      some of these trends, deferred childbearing, increasing population rates of
      coexisting disease, multifetal pregnancy, and emerging infections also
      contribute. Risk is markedly elevated among certain racial and ethnic minorities,
      due to a confluence of factors that includes behavior, biology, environmental
      exposures, social circumstances, and the quality of clinical care. Approximately
      30-40% of maternal deaths are potentially preventable, and recent maternal
      mortality reviews suggest specific strategies that may improve outcomes for women
      suffering from the most common causes of death: cardiovascular disease,
      hemorrhage, hypertensive disorders of pregnancy, venous thromboembolism,
      infection, and other medical conditions. SUMMARY: A growing number of countries
      and organizations have established systems for comprehensive maternal death
      surveillance and confidential review to ensure that each death counts and that
      the lessons learned are widely disseminated to improve future maternal safety.

PMID- 22459983
TI  - Cesarean delivery fluid management.
AB  - PURPOSE OF REVIEW: To guide the optimal fluid management during cesarean
      delivery. The article focuses on fluid management to prevent hypotension during
      cesarean delivery performed under spinal anesthesia and excludes obstetric
      hemorrhage. RECENT FINDINGS: The literature underlines that crystalloid
      preloading is ineffective or poorly effective to prevent spinal hypotension
      during cesarean delivery. Crystalloid coloading is better but the effectiveness
      reported is variable and may depend on the volume used and the speed of
      administration at onset of sympathetic blockade. Hydroxyethyl starch (HES)
      preloading is more consistently effective in reducing the incidence and severity
      of hypotension. HES coloading appears as effective as HES preloading. Because
      none of these fluid-loading methods is completely effective at preventing
      hypotension, some sort of prophylactic vasopressor regimen should always be
      added. Routine fluid loading is no longer advocated prior to spinal anesthesia
      for cesarean delivery in preeclampsia and should be used with caution in women
      with multiple gestations. SUMMARY: Current evidence suggests that combining a
      prophylactic vasopressor regimen with HES preloading, HES coloading or
      crystalloid coloading is the best method of preventing maternal hypotension after
      the initiation of spinal anesthesia. Crystalloid preloading is clinically
      ineffective and thus should no longer be used.

PMID- 22459984
TI  - The anesthesiologist and end-of-life care.
AB  - PURPOSE OF REVIEW: Anesthesiologists may face problematic situations when
      patients are close to death, in which clinical problems, decision-making
      processes, and ethical issues are often interconnected and dependent on each of
      them. The aim of this review is to assess the recent literature regarding the
      anesthesiological role for advanced cancer patients. RECENT FINDINGS: Palliative
      sedation in the dying patients, end-of-life problems in the ICU, and pain control
      in advanced cancer patients have been the subject of recent research. All these
      issues have shown that anesthesiologist would be expert in the field of pain and
      symptom control at the end of life. End-of-life care problems are common in ICU,
      and a decision-making process requires knowledge and management of patients'
      wishes, past and projected future quality of life, severity and prognosis of
      illness, patients' age, regarding withholding and withdrawing of futile
      treatments in anticipation of death, or relieving symptoms close to death.
      SUMMARY: Anesthesiologists should be competent in all aspects of terminal care,
      including the practical and ethical aspects of withdrawing different modalities
      of life-sustaining treatment and the use of sedatives, analgesics, and
      nonpharmacologic approaches to easing the suffering of the dying process. More
      research is needed to provide models which should be spread in the scientific
      community to afford this difficult task.

PMID- 22459985
TI  - Should antifibrinolytics be given in all patients with trauma?
AB  - PURPOSE OF REVIEW: Hemorrhage is the second most important cause of death in
      patients with trauma, contributing to approximately 30% of trauma-related
      mortality. Pharmacological prohemostatic agents may be useful adjunctive
      treatment options in patients with severe blood loss. RECENT FINDINGS: Tranexamic
      acid was evaluated in a large international randomized controlled study in
      patients with trauma and severe blood loss. The drug was shown to reduce death
      due to bleeding, provided the treatment was given within 3 h after injury.
      Tranexamic acid treatment did not result in serious adverse events nor thrombotic
      complications. SUMMARY: In view of this efficacy and safety of this relatively
      cheap and simple drug, it may be recommended to put tranexamic acid in the first
      (maybe even prehospital) line of management of patients with severe traumatic
      hemorrhage.

PMID- 22459986
TI  - Diabetes care: Opinions, needs and proposed solutions of Swiss patients and
      healthcare professionals: a qualitative study.
AB  - AIMS: To explore, both among patients with diabetes and healthcare professionals,
      opinions on current diabetes care and the development of the "Regional Diabetes
      Program". METHODS: We employed qualitative methods (focus groups - FG) and used
      purposive sampling strategy to recruit patients with diabetes and healthcare
      professionals. We conducted one diabetic and one professional FG in each of the
      four health regions of the canton of Vaud/Switzerland. The eight FGs were audio
      taped and transcribed verbatim. Thematic analysis was then undertaken. RESULTS:
      Results showed variability in the perception of the quality of diabetes care,
      pointed to insufficient information regarding diabetes, and lack of
      collaboration. Participants also evoked patients' difficulties for self
      management, as well as professionals' and patients' financial concerns. Proposed
      solutions included reinforcing existing structures, developing self-management
      education, and focusing on comprehensive and coordinated care, communication and
      teamwork. Patients and professionals were in favour of a "Regional Diabetes
      Program" tailored to the actors' needs, and viewed it as a means to reinforce
      existing care delivery. CONCLUSIONS: Patients and professionals pointed out
      similar problems and solutions but explored them differently. Combined with
      coming quantitative data, these results should help to further develop, adapt and
      implement the "Regional Diabetes Program".

PMID- 22459987
TI  - Quantification of concordance and discordance between apolipoprotein-B and the
      currently recommended non-HDL-cholesterol goals for cardiovascular risk
      assessment in patients with diabetes and hypertriglyceridemia.
AB  - AIMS: In patients with diabetes and hypertriglyceridemia, LDL-cholesterol (LDL-C)
      provides an inaccurate reflection of LDL particle burden. The relative value of
      non-HDL-cholesterol (non-HDL-C) and apolipoprotein-B (Apo-B) in estimating
      cardiovascular risk is controversial. We assessed the discordance between non-HDL
      C and Apo-B targets in patients with diabetes with TG 200-499 mg/dl. METHODS:
      Data from 1430 determinations of LDL-C, non-HDL-C, and Apo-B in ambulatory
      patients with diabetes were analyzed. Rates of discordance were calculated, based
      on the currently recommended LDL-C, non-HDL-C, and Apo-B goals. RESULTS: In
      patients with non-HDL-C goal of <130 mg/dl, there was a discordance with Apo-B
      level goal of <90 mg/dl, in 31% of samples. In patients with non-HDL-C goal of
      <100 mg/dl, 6% of samples had Apo-B >=80 and 18% had Apo-B <80 mg/dl. Using the
      Apo-B goal of <70 mg/dl, these numbers were 37% and 3.5% respectively. There was
      also a significant gender difference, i.e. under-estimation of risk by suggested
      non-HDL-C cut-offs, in females, compared to males. CONCLUSIONS: In patients with
      diabetes and hypertriglyceridemia, a considerable discordance exists between non
      HDL-C and Apo-B. Our data suggest a need for prospective studies to compare the
      relative merits of non-HDL-C and Apo-B targets in the assessment of
      cardiovascular risk.

PMID- 22459988
TI  - [Endocrine disorders in a polymedicated patient].

PMID- 22459989
TI  - Association of parathyroid pathology with well-differentiated thyroid carcinoma.
AB  - OBJECTIVE: The objective was to evaluate the association of well-differentiated
      thyroid carcinoma and parathyroid pathology. METHODS: The medical records of 14
      patients with concomitant pathologies were retrospectively reviewed. RESULTS:
      Parathyroidectomies (1.3%) and thyroidectomies (3.5%) performed for well
      differentiated thyroid carcinoma resulted in the diagnosis of concomitant
      pathologies. Five patients had a primary hyperparathyroidism (PHPT) and nine were
      operated for thyroidectomy with intraoperative finding of an enlarged parathyroid
      gland. Patients (64%) were normocalcemic preoperatively. Thirteen had papillary
      carcinoma. Fifty percent of patients had multiple foci of papillary
      microcarcinoma. Twenty-nine percent of patients had parathyroid hyperplasia. All
      patients with preoperative hypercalcemia normalized their serum calcium. During
      follow-up, thyroglobuline, calcium serum values and cervical ultrasound showed no
      evidence of recurrence of the diseases. CONCLUSIONS: These observations stress
      the importance of pre and intraoperative evaluation to detect overt thyroid and
      parathyroid pathology before performing a parathyroidectomy for
      hyperparathyroidism or a thyroidectomy for a well-differentiated thyroid
      carcinoma.

PMID- 22459990
TI  - Gender-related analysis of the clinical presentation, treatment response and
      outcome in patients with immune thrombocytopenia.
AB  - BACKGROUND: Immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP])
      frequently occurs in young adults, particularly women in their third or fourth
      decade. The female predominance suggests that sex hormones may play a role in the
      different aspects of ITP. In this paper, we report a gender-related analysis of
      patients with ITP, specifically examining the clinical manifestations, responses
      to treatment and overall outcomes of the patients. METHODS: We included patients
      with "ITP" attending the departments of onco-hematology or internal medicine B
      (university hospital of Strasbourg, France) between 1990 and December 2010 The
      gender-related analysis was retrospective. RESULTS: We studied in 225 consecutive
      cases of established ITP with a follow-up period of 1.7 to 112 months The mean
      age of the patients was 44 years; 156 patients were female. The analysis revealed
      no significant statistical differences regarding patient characteristics between
      the female and male groups, with the exception of the following characteristics:
      the bleeding score, which altered in the presence of meno- and/or metrorrhagia
      and hematuria in female patients (P=0.03); the presence of anemia (P=0.04); and
      the detection of antinuclear and/or antiphospholipid antibodies (P=0.02). During
      the follow-up, no statistically significant difference was found regarding
      outcome or treatment response in relation to gender among these 225 patients (all
      P>0.05). DISCUSSION: Gender does not appear to affect the manifestation of immune
      thrombocytopenia, the outcome or response to treatment. However, further large
      scale randomized trials are needed to confirm these findings.

PMID- 22459991
TI  - [Operability of databases].

PMID- 22459992
TI  - [Relationships between patient associations and companies: ethical aspects].

PMID- 22459993
TI  - [Interest in partnerships around the Mediterranean basin for rare diseases].

PMID- 22459994
TI  - [Cerebral hyperperfusion syndrome after carotid revascularization].

PMID- 22459995
TI  - Endosulfan exposure inhibits brain AChE activity and impairs swimming performance
      in adult zebrafish (Danio rerio).
AB  - Endosulfan is a broad spectrum organochlorine pesticide that is still widely in
      use in many developing countries. Following application, endosulfan can get to
      watercourses through surface runoff from agricultural fields and disturb the non
      target aquatic animals including freshwater fish species. Given that the activity
      of the enzyme acetylcholinesterase (AChE) is one of the most recurrently used
      biomarkers of exposure to pesticides and there are controversial results
      concerning the effects of endosulfan exposure and AChE activity in fish, the aim
      of the present study was to evaluate the effects of endosulfan in brain AChE
      activity and its gene expression pattern using adult zebrafish (Danio rerio) as
      an animal model. Moreover, we have analyzed the effects of endosulfan exposure in
      different parameters of zebrafish swimming activity and in long-term memory
      formation. After 96 h of exposition, fish in the 2.4 MUg endosulfan/L group
      presented a significant decrease in AChE activity (9.44 +/- 1.038 MUmol SCh h(-1)
      mg protein(-1); p=0.0205) when compared to the control group (15.87 +/- 1.768
      MUmol SCh h(-1) mg protein(-1); p=0.0205) which corresponds to approximately 40%.
      The down-regulation of brain AChE activity is not directly related with the
      transcriptional control as demonstrated by the RT-qPCR analysis. Our results
      reinforce AChE activity inhibition as a pathway of endosulfan-induced toxicity in
      brain of fish species. In addition, exposure to 2.4 MUg endosulfan/L during 96 h
      impaired all exploratory parameters evaluated: decreased line crossings (~21%,
      273.7 +/- 28.12 number of line crossings compared to the control group 344.6 +/-
      21.30, p=0.0483), traveled distance (~20%, 23.44 +/- 2.127 m compared to the
      control group 29.39 +/- 1.585, p=0.0281), mean speed (~25%, 0.03 +/- 0.003 m/s
      compared to the control group 0.04 +/- 0.002, p=0.0275) and body turn angle
      (~21%, 69,940 +/- 4871 absolute turn angle compared to the control group 88,010
      +/- 4560, p=0.0114). These results suggest that endosulfan exposure significantly
      impairs animals' exploratory performance, and potentially compromises their
      ecological and interspecific interaction. Our results also showed that the same
      endosulfan exposure did not compromise animals' performance in the inhibitory
      avoidance apparatus. These findings provide further evidence of the deleterious
      effects of endosulfan exposure in the nervous system.

PMID- 22459996
TI  - Low-dose venlafaxine-induced severe rhabdomyolysis: a case report.
AB  - Venlafaxine is a relatively new antidepressant with selective effects. Compared
      with traditional antidepressants, this agent has fewer adverse side effects.
      However, venlafaxine overdose has been reported with severe complications such as
      seizure, ventricular tachycardia, serotonin syndrome, neuroleptic malignant
      syndrome and rhabdomyolysis. We present a 21-year-old female with bipolar
      depression who took a low dose of venlafaxine, but subsequently developed severe
      rhabdomyolysis. Her plasma level of creatine kinase increased up to 18,711 U/L in
      few days. These findings may serve as a reminder to physicians to be alert to the
      possibility of rhabdomyolysis in patients who have only taken a low dose of
      venlafaxine.

PMID- 22459997
TI  - Type D personality is associated with increased comorbidity burden and health
      care utilization among 3080 cancer survivors.
AB  - OBJECTIVE: Cancer survivors often report comorbid diseases, but there are
      individual differences in risk. Type D personality is a general propensity to
      psychological distress that is related to poor cardiovascular outcomes. In this
      study, we examined whether type D was also related to comorbidity burden and
      health care utilization among cancer survivors. METHODS: Individuals diagnosed
      with endometrial cancer or colorectal cancer between 1998 and 2007, or with
      lymphoma or multiple myeloma between 1999 and 2008 as registered in the Eindhoven
      Cancer Registry, received the Self-Administered Comorbidity Questionnaire,
      questions on health care utilization and the Type D personality scale; 69%
      (n=3080) responded. RESULTS: Nineteen percent of survivors had a type D
      personality. Over a 12-month period, type D survivors significantly more often
      reported osteoarthritis, back pain, and depression than non-type D survivors.
      Also, type D survivors more often reported to feel bothered by high blood
      pressure, osteoarthritis, heart disease, depression, diabetes and lung disease
      during daily activities. Type D survivors more often visited their general
      practitioner than non-type D survivors (P<.001), also in relation to cancer (0
      visits: 54% vs. 60%; 1-5: 28% vs. 22%; >5: 9% vs. 5%; P<.001), as well as their
      specialist (0 visits: 6% vs. 7%; 1-5 visits: 59% vs. 64%; >5 visits: 30% vs. 23%;
      P<.01). CONCLUSION: Type D personality is a vulnerability factor that may help to
      identify subgroups of cancer survivors who are at an increased risk for
      comorbidity burden and increased health care utilization.

PMID- 22459998
TI  - The prevalence of somatoform disorders in internal medicine outpatient
      departments of 23 general hospitals in Shenyang, China.
AB  - OBJECTIVE: The objective was to assess the prevalence, demographics and risk
      factors of somatoform disorders (SDs) in departments of internal medicine at 23
      randomly selected general hospitals in Shenyang, China. METHOD: A two-stage
      screening process was followed based on an expanded Chinese version of the 12
      item General Health Questionnaire and the Structured Clinical Interview for DSM
      IV-TR Axis I Disorders . A total of 5312 consecutive attendees of the outpatient
      at the departments of internal medicine were screened; 60 patients of 15 years or
      older were confirmed to have current SDs. RESULTS: The 1-month prevalence of any
      type of SD was 1.56% [95% confidence interval (CI): 1.19%-2.02%], and those of
      undifferentiated SD, pain disorder, hypochondriasis and somatization disorder
      were 0.68% (0.47%-0.98%), 0.44% (0.15%-1.26%), 0.38% (0.22%-0.64%) and 0.06%
      (0.02%-0.20%), respectively. The prevalence of any SD and two types of SDs was
      higher in females than in males: relative risk (95% CI) for any SD=1.82 (1.11
      2.97), for pain disorder=12.70 (1.63-99.19). CONCLUSION: The prevalence of SDs
      among outpatients at urban China's internal medicine departments is lower than
      that reported in most Western countries. SDs were more prevalent among female
      outpatients at general hospitals.

PMID- 22459999
TI  - Physical complications of severe, chronic obsessive-compulsive disorder: a
      comparison with general psychiatric inpatients.
AB  - BACKGROUND: This research examines the physical health of patients with severe,
      chronic obsessive-compulsive disorder (OCD) and compares the findings with
      patients admitted to an acute general psychiatric ward. METHODS: Successive
      admissions to a specialist inpatient unit treating patients with OCD were
      included in the study. Information including gender, age, weight and height were
      recorded along with the results of blood tests for urea, liver function tests and
      blood lipids. In addition, type and dose of medication were also recorded. These
      data were compared with information obtained via the case records from successive
      admissions to a general psychiatric ward. RESULTS: A total of 104 patients with
      OCD and 101 patients admitted to an acute psychiatric unit were studied. OCD
      patients were generally younger than the controls and were on a lower dose of
      antipsychotic medication. Despite this, the OCD patients were more likely than
      the general psychiatric patients to have raised blood lipids. Raised creatinine
      was also more common among OCD patients. CONCLUSION: The study demonstrates that
      patients with severe OCD have significant evidence of serious physical health
      problems.

PMID- 22460000
TI  - Early neuropsychiatric involvement in antiphospholipid syndrome.
AB  - OBJECTIVE: Neuropsychiatric symptoms may be the main manifestations and very
      early symptoms of developing autoimmune diseases. Early detection and treatment
      could reverse psychotic symptoms and restore cognitive function. CASE REPORT: A
      24-year-old woman presented with acute psychotic symptoms. Routine physical
      examinations revealed only mild fever. Due to positive antiphospholipid
      antibodies, low protein S with elevated d-dimer and brain hypoperfusion, early
      phase antiphospholipid syndrome (APS) was suspected. Early immunomodulation
      treatment led to complete remission of the psychotic symptoms, preservation of
      cognitive function and prevention of APS progression. CONCLUSION: Since early
      detection and treatment can reverse the progression of autoimmune diseases with
      central nervous system involvement, these should be highlighted when managing
      high-risk patients.

PMID- 22460002
TI  - Hyperlipidemia in patients with schizophrenia: a national population-based study.
AB  - OBJECTIVE: The objective was to examine hyperlipidemia among Taiwanese patients
      with schizophrenia. METHODS: We obtained a random sample of 766,427 subjects aged
      >=18 years in 2005. Subjects with at least one primary diagnosis of schizophrenia
      and with a primary or secondary diagnosis of hyperlipidemia or medication for
      hyperlipidemia were identified. We compared the prevalence and incidence of
      hyperlipidemia in schizophrenic patients with the general population. RESULTS:
      The prevalence of hyperlipidemia in patients with schizophrenia was higher than
      that in the general population (8.15% vs. 8.10%; odds ratio 1.17; 95% confidence
      interval, 1.04-1.31) in 2005. Compared with the general population, schizophrenic
      patients had a higher prevalence of hyperlipidemia in individuals aged <50 years,
      among those with higher insurance amount, and among persons living in northern
      and central regions and in urban areas. The average annual incidence of
      hyperlipidemia in schizophrenic patients with second-generation antipsychotic use
      from 2006 to 2008 was higher than that in the general population (1.57% vs.
      1.29%; odds ratio 1.31; 95% confidence interval, 1.11-1.55). CONCLUSIONS:
      Patients with schizophrenia had a much higher prevalence of hyperlipidemia in
      young adulthood than that in the general population. Schizophrenic patients with
      second-generation antipsychotic exposure had a higher incidence of hyperlipidemia
      than individuals in the general population.

PMID- 22460001
TI  - Abbreviated PTSD Checklist (PCL) as a guide to clinical response.
AB  - OBJECTIVE: The objective of this study was to evaluate two abbreviated versions
      of the PTSD Checklist (PCL), a self-report measure of posttraumatic stress
      disorder (PTSD) symptoms, as an index of change related to treatment. METHOD:
      Data for this study were from 181 primary care patients diagnosed with PTSD who
      enrolled in a large randomized trial. These individuals received a collaborative
      care intervention (cognitive behavioral therapy (CBT) and/or medication) or usual
      care and were followed 6 and 12 months later to assess their symptoms and
      functioning. The sensitivity of the PCL versions (i.e., full, two-item, six
      item), correlations between the PCL versions and other measures, and use of each
      as indicators of reliable and clinically significant change were evaluated.
      RESULTS: All versions had high sensitivity (.92-.99). Correlations among the
      three versions were high, but the six-item version corresponded more closely to
      the full version. Both shortened versions were adequate indicators of reliable
      and clinically significant change. CONCLUSION: Whereas prior research has shown
      the two-item or six-item versions of the PCL to be good PTSD screening
      instruments for primary care settings, the six-item version appears to be the
      better alternative for tracking treatment-related change.

PMID- 22460003
TI  - Antipsychotic polypharmacy: a needle in a haystack?
AB  - OBJECTIVE: The aim of our study was to assess the antipsychotic polypharmacy
      (APP) prevalence in a psychiatric hospital and to find the supporting evidence
      for the 10 most prescribed two-drug combinations. Secondarily, how many included
      clozapine, prevalence in the elderly, high dosage and clinically relevant
      interactions were also assessed. METHOD: Clinicodemographic and computerized
      prescription data on 29th March 2011 were collected. High dosage was defined as
      more than 1000 mg of chlorpromazine equivalents (CPZeqs). A t test for unpaired
      measures was applied to compare means of dosage (CPZeq) and age among patients on
      APP vs. monotherapy. The chi(2) test was applied to compare proportions of
      patients on a high dose on APP vs. monotherapy. GraphPad Prism 5 software was
      used to perform statistical analysis. RESULTS: From 201 patients admitted on 29th
      March, 172 had any antipsychotic prescription. APP prevalence was 47.1%,
      corresponding almost to 24% of elderly patients. Quetiapine was the drug most
      prescribed in combination, achieving a prevalence rate of 56.8%. Clozapine was
      not included in 67% of all combinations. Supporting evidence for two-drug
      combinations was only found for 6 of the 10 most prescribed. Relevant
      interactions were found in 12 patients on APP. The mean CPZeq dose and percentage
      of patients on high dosage were significantly higher in the APP than in the
      monotherapy group (1162+/-776.1 mg vs. 455.4+/-369.3 mg; 54% vs. 9%,
      respectively; P<.0001). CONCLUSIONS: Our study shows that APP was being
      considered earlier in the management plan than what guidelines recommend. This
      practice was associated with higher total antipsychotic doses. Until further
      clinical trials are available, a wise APP practice will require a thoughtful
      choice of products guided by patient's prior history and interaction liability, a
      proper consent by the patients or their representatives and a careful monitoring
      of clinical outcomes and emerging side effects in order to avoid indefinite
      administration of ineffective and potentially harmful combinations.

PMID- 22460004
TI  - Changes in cardiovascular disease burden associated with psychopathology in
      Australian adults 2004-2008.
AB  - OBJECTIVE: The objective was to investigate changes in self-reported
      cardiovascular disease (CVD) burden associated with psychopathology for Australia
      from 2004 to 2008. METHOD: Data analyzed were from 32,073 participants aged >=25
      years from the 2004-2005 or 2007-2008 National Health Surveys. Lifetime diagnosis
      of CVD (heart attack or stroke) was by self-report. Psychopathology was
      determined by the 10-item Kessler Psychological Distress Scale (using scores
      >=30) and use of antidepressants or antianxiety (AD/AA) medications. RESULTS: The
      prevalence of CVD (4.1% to 4.5%, P=.045) had increased slightly from 2004 to 2008
      for the general population, but not among those with psychopathology. On average,
      psychological distress only [odds ratio (OR) 2.00; 95% confidence interval, 1.52
      2.62] and AD/AA medications with (OR 2.02; 1.41-2.88) and without psychological
      distress (OR 1.24; 1.00-1.55) were associated with increased odds of CVD over the
      4-year period, independent of sociodemographic, lifestyle and chronic disease
      covariates. Both psychological distress only (OR 1.61; 1.15-2.25) and AD/AA
      medications with psychological distress (OR 1.62; 1.08-2.44) conferred higher
      odds of CVD than AD/AA medications without psychological distress. CONCLUSION: In
      comparison to those without psychopathology, the odds of self-reported CVD were
      persistently higher among people with psychopathology from 2004 to 2008,
      particularly for psychological distress.

PMID- 22460005
TI  - Juvenile Huntington's disease presenting as difficult-to-treat seizure and the
      first episode of psychosis.
AB  - OBJECTIVE: The objective was to describe a case of juvenile Huntington's disease
      that first presented with seizures and psychosis. METHODS: A male patient with no
      history of epilepsy and psychiatric disorder had his first seizure at the age of
      20 years, which was followed by 3 years of psychotic disorder. RESULTS:
      Laboratory investigations were normal, and mild diffuse cortical atrophy was
      detected using magnetic resonance imaging. Both the seizures and psychosis were
      difficult to treat. Three years later, chorea and personality changes appeared.
      Genetic tests revealed an expanded allele with 60 CAG repeats, confirming the
      typical Huntington's disease characteristic. CONCLUSION: Patients with difficult
      to-treat seizures and the first episode of psychosis should be considered for the
      diagnosis of juvenile Huntington's disease.

PMID- 22460006
TI  - Prevalence of physical symptoms and their association with race/ethnicity and
      acculturation in the United States.
AB  - OBJECTIVE: Physical symptoms are common and a leading reason for primary care
      visits; however, data are lacking on their prevalence among racial/ethnic
      minorities in the United States. This study aimed to compare the prevalence of
      physical symptoms among White, Latino and Asian Americans, and examine the
      association of symptoms and acculturation. METHODS: We analyzed data from the
      National Latino and Asian American Study, a nationally representative survey of
      4864 White, Latino and Asian American adults. We compared the age- and gender
      adjusted prevalence of 14 physical symptoms among the racial/ethnic groups and
      estimated the association between indicators of acculturation (English
      proficiency, nativity, generational status and proportion of lifetime in the
      United States) and symptoms among Latino and Asian Americans. RESULTS: After
      adjusting for age and gender, the mean number of symptoms was similar for Whites
      (1.00) and Latinos (0.95) but significantly lower among Asian Americans (0.60,
      P<.01 versus Whites). Similar percentages of Whites (15.4%) and Latinos (13.0%)
      reported three or more symptoms, whereas significantly fewer Asian Americans
      (7.7%, P<.05 versus Whites) did. In models adjusted for sociodemographic
      variables and clinical status (psychological distress, medical conditions and
      disability), acculturation was significantly associated with physical symptoms
      among both Latino and Asian Americans, such that the most acculturated
      individuals had the most physical symptoms. CONCLUSIONS: The prevalence of
      physical symptoms differs across racial/ethnic groups, with Asian Americans
      reporting fewer symptoms than Whites. Consistent with a "healthy immigrant"
      effect, increased acculturation was strongly associated with greater symptom
      burden among both Latino and Asian Americans.

PMID- 22460007
TI  - The implementation of a new Malaria Treatment Protocol in Timor-Leste: challenges
      and constraints.
AB  - BACKGROUND: Timor-Leste changed its malaria treatment protocol in 2007, replacing
      the first-line for falciparum malaria from sulphadoxine-pyrimethamine to
      artemether-lumefantrine. This study explored the factors affecting the
      implementation of the revised treatment protocol, with an emphasis on identifying
      key constraints. METHODS: A mixed method approach drew on both qualitative and
      quantitative data. The study included data from District Health Services in seven
      districts, community health centres in 14 sub-districts, four hospitals, five
      private clinics, one private pharmacy and the country's autonomous medical store.
      In-depth interviews with 36 key informants, five group interviews and 15 focus
      group discussions were conducted. A survey was also undertaken at community
      health centres and hospitals to assess the availability of a physical copy of the
      Malaria Treatment Protocol, as well as the availability and utilization of
      artemether-lumefantrine and sulphadoxine-pyrimethamine. RESULTS: Many factors
      impeded the implementation of the new malaria protocol. These included:
      inadequate introduction and training around the revised treatment protocol;
      unclear phasing out of sulphadoxine-pyrimethamine and phasing in of the revised
      treatment, artemether-lumefantrine, and the rapid diagnostic test (RDT); lack of
      supervision; lack of adherence to the revised guidelines by foreign health
      workers; lack of access to the new drug by the private sector; obstacles in the
      procurement process; and the use of trade names rather than generic drug
      description. Insufficient understanding of the rapid diagnostic test and the
      untimely supply of drugs further hampered implementation. CONCLUSION: To
      effectively implement a revised malaria treatment protocol, barriers should be
      identified during the policy formulation process and those emerging during
      implementation should be recognized promptly and addressed.

PMID- 22460009
TI  - From the Editor-in-Chief.

PMID- 22460008
TI  - Improved compressed sensing-based cone-beam CT reconstruction using adaptive
      prior image constraints.
AB  - Volumetric cone-beam CT (CBCT) images are acquired repeatedly during a course of
      radiation therapy and a natural question to ask is whether CBCT images obtained
      earlier in the process can be utilized as prior knowledge to reduce patient
      imaging dose in subsequent scans. The purpose of this work is to develop an
      adaptive prior image constrained compressed sensing (APICCS) method to solve this
      problem. Reconstructed images using full projections are taken on the first day
      of radiation therapy treatment and are used as prior images. The subsequent scans
      are acquired using a protocol of sparse projections. In the proposed APICCS
      algorithm, the prior images are utilized as an initial guess and are incorporated
      into the objective function in the compressed sensing (CS)-based iterative
      reconstruction process. Furthermore, the prior information is employed to detect
      any possible mismatched regions between the prior and current images for improved
      reconstruction. For this purpose, the prior images and the reconstructed images
      are classified into three anatomical regions: air, soft tissue and bone.
      Mismatched regions are identified by local differences of the corresponding
      groups in the two classified sets of images. A distance transformation is then
      introduced to convert the information into an adaptive voxel-dependent relaxation
      map. In constructing the relaxation map, the matched regions (unchanged anatomy)
      between the prior and current images are assigned with smaller weight values,
      which are translated into less influence on the CS iterative reconstruction
      process. On the other hand, the mismatched regions (changed anatomy) are
      associated with larger values and the regions are updated more by the new
      projection data, thus avoiding any possible adverse effects of prior images. The
      APICCS approach was systematically assessed by using patient data acquired under
      standard and low-dose protocols for qualitative and quantitative comparisons. The
      APICCS method provides an effective way for us to enhance the image quality at
      the matched regions between the prior and current images compared to the existing
      PICCS algorithm. Compared to the current CBCT imaging protocols, the APICCS
      algorithm allows an imaging dose reduction of 10-40 times due to the greatly
      reduced number of projections and lower x-ray tube current level coming from the
      low-dose protocol.

PMID- 22460010
TI  - Severe osteoporosis: diagnosis of non-hip non-vertebral (NHNV) fractures.
AB  - Osteoporotic bone, structurally altered because of reduction of bone mineral
      density and quality deterioration, can easily head for fracture after minimum
      mechanical stress.THE MOST COMMON SITES OF FRACTURE, OTHER THAN SPINE AND HIP,
      ARE, IN DECREASING ORDER: distal radius, forearm, proximal humerus, other femoral
      sites, ribs, pelvis, tibia and fibula, metatarsal bone and calcaneum. The role of
      diagnostic imaging is essential in detecting fractures for their immediate and
      correct assessment, which is necessary to the planning of treatment, whether
      conservative or surgical. Imaging is also important in fracture monitoring,
      evaluation of healing and relief of any complications.Conventional radiology is
      the most widely used technique in the diagnosis of fracture, although its low
      sensitivity, mainly in anatomically complex sites; the role of radiology is
      undisputed in monitoring the healing bone callus formation. Multidetector
      Computed Tomography (MDCT) is of great help in doubtful cases, especially in
      locations as "critical"; its diagnostic accuracy is very elevated with 3D and
      multi-planar reconstructions, allowing the surgeon to implement an appropriate
      therapeutic strategy. Magnetic Resonance (MR) is the most sensitive technique in
      the relief of minimal structural alteration of the cancellous bone, as it reveals
      both fracture line and surrounding bone marrow oedema. Its specificity is higher
      compared to MDCT and conventional radiology in the differential diagnosis between
      osteoporotic and malignancy pathological fracture.Bone scintigraphy is
      complementary to MRI in detecting occult fractures, crucial in finding metastatic
      disease in other locations. Ultrasound is used in limited districts, and its role
      is confined to the relief of cortical interruption in the fractured bone segment.
      In the future, technological advances with three-dimensional techniques (hr-CT,
      hr-MRI) may improve in vivo the diagnostic potential with an earlier detection of
      the ultrastructural alterations that predispose to the risk of bone fracture.

PMID- 22460011
TI  - Radial extracorporeal shock-wave therapy in rotator cuff calcific tendinosis.
AB  - The objective of the study is to evaluate the effectiveness of Radial
      Extracorporeal Shock-wave Therapy (RESWT) compared with High Power LASER Therapy
      (HPLT) for the treatment of patients with Rotator Cuff Calcific Tendinosis
      (RCCT). RCCT is widely diffused, it is painful and invalidating. It is an
      important public health problem with social and economic implications. The most
      common therapeutic approach is a physiotherapic one. Both HPLT and RESWT give
      positive results. There is a debate on which is to be preferred. Therefore there
      is need to obtain scientific evidence to support either case. An observational
      study was carried out in the period between October 2008 and September 2009 in
      our outpatient clinic with 62 patients, divided into 3 groups: group A 36
      patients treated only with RESWT, group B 26 patients treated only with HPLT and
      group C 16 patients with only short term improvement with HPLT retreated with
      RESWT. Patients were evaluated with Constant-Murley scale before and after
      treatment (immediately, 1 month and 3 months) for mean constant score, pain and
      range of movement. Data were examined statistically with SPSS. Criteria for
      inclusion and exclusion were defined. Patients treated with HPLT have shown good
      clinical results but have returned to original syndrome 1 month after treatment.
      RESWT has given improvement after treatment extended in time (3 months) in terms
      of pain and recover of functionality with a limited number of applications. The
      evidence collected indicates that RESWT is the method of choice.

PMID- 22460012
TI  - Severe osteoporosis: diagnosis of femoral fractures.
AB  - In the diagnosis of femoral fractures, Radiodiagnostic has a role in the
      different phases of the natural history of these lesions:- in diagnosis and
      characterization of fractures,- in follow up of the efficacy of therapy,
      evolution of fractures and any complications,- in studies of risk factors of
      fractures.Diagnostic imaging employs method of investigation as Conventional
      Radiology, still crucial in detection, characterization and control of fracture,
      Computed Tomography (CT) and Magnetic Resonance (MR), essential in doubt of
      occult fracture and in differential diagnosis between the possible causes of
      pathologic fracture. Finally, Dual X-ray Absorptiometry (DXA is still the
      fundamental methodic in diagnosis and assessment of osteoporosis, while QCT, pQCT
      and HR-CT are experimental techniques used to study in vivo bone
      microarchitecture and its metabolic and pathological changes.

PMID- 22460013
TI  - Evaluation of bone density in infancy and adolescence. Review of medical
      literature and personal experience.
AB  - The evolution of medical and surgical therapies allows the increased survival
      rate of a growing number of children affected by rare pathologies. In this light
      osteoporotic disease is also of orthopaedic interest as it is sometimes the
      outward manifestation of serious pathologies (i.e. osteogenesis imperfecta).
      Sometimes, even in infancy and adolescence, osteoporosis is associated with
      complications due to fractures; in other cases it seems to have no immediate
      consequence. Nevertheless it must be considered as a fracture risk factor in
      adulthood as it negatively affects the achievement of peak bone mass. The
      evaluation of variations in bone mass that take place during growth is thus of
      particular importance in order to guarantee a level of bone health suitable for
      the next phase. These remarks compose the premise of a study on bone resistance
      carried out on a study population of between 6 and 18 years of age in the city of
      Pavia. To determine the resistance of the bone an ultrasound device was employed
      (OmnisenseTM , Sunlight Medical Ltd, Tel Aviv, Israel) in two skeletal sites,
      distal radius and midshaft of tibia. The analysis of our results and a review of
      the relevant literature indicate that the median values of normality, against
      which we compare the measurements of the patients under examination, depend not
      only on age, sex, skeletal sites, race, and even ethnic group. The introduction
      of this new parameter, to be kept in mind when interpreting the results, invites
      us to be very prudent in determining the diagnostic threshold values in
      paediatric age. As with anthropometric data (weight, height, cranial
      circumference) it is possible to suggest an interpretation of the patient's SOS
      values comparing them with the 'centile curves' typical to the region the child
      belongs to. Of course, further studies are required to understand what are the
      variables involved and to determine the extension of the geographical area to be
      examined to obtain suitable reference curves.

PMID- 22460014
TI  - The effectiveness and safety of vertebroplasty for osteoporotic vertebral
      compression fractures. A double blind, prospective, randomized, controlled study.
AB  - BACKGROUND: Vertebral compression fractures (VCFs) constitute a major health care
      problem in western countries. Several treatments modalities are available to
      relieve pain and allow increased activities. Percutaneous vertebroplasty (the
      injection of bone cement into the fractured vertebral body) is a relatively new
      procedure to manage patients with these fractures. The aim of this study is to
      evaluate the efficacy and safety of percutaneous vertebroplasty compared with
      standard conservative care. METHODS/DESIGNS: In this double blind, prospective,
      randomized, controlled study the short- (3 months), medium- (6 months) and long
      term (24 months) efficacy and safety of vertebroplasty to alleviate pain and
      improve function for painful osteoporotic vertebral fractures will be compared to
      standard conservative therapy. Conservative care will consist of 3 weeks of bed
      rest, wearing a rigid hyperextension corset, followed by 2-3 months in a Cheneau
      brace. In each of the two groups, patients will also receive treatment for
      osteoporosis according to their metabolic profile. Two hundred patients with
      painful osteoporotic vertebral compression fractures will be recruited over a 3
      year period according to inclusion and exclusion criteria. We will randomly
      assign participants to receive either vertebroplasty or conservative care.
      Subjects will complete a battery of validated, standardized measures of pain,
      functional disability, and health related quality of life questionnaires at
      baseline and at post-randomization time points (1, 3, 6, 12 and 24 months). Each
      patient will be evaluated for pre-operative MRI, and pre- and post-operative
      radiographs; all scans will be evaluated independently by 2 orthopaedic surgeons.
      Laboratory tests to assess their metabolic bone profile will be also performed.
      Our primary outcome will be change from baseline to 1, 3, 6, 12 and 24 months in
      the VAS score between the 2 groups. DISCUSSION: To date, vertebroplasty has been
      not been compared with standard conservative care for the management of patients
      with painful osteoporotic vertebral fractures in a randomised controlled trial.
      Therefore, the results of this study will allow to draw firm conclusions on this
      controversial topic.

PMID- 22460015
TI  - Appropriate use of anabolic treatment for severe osteoporosis.
AB  - Osteoporotic fractures remain a major public health problem for their correlated
      morbidity and mortality. The primary aim of therapy must be the prevention of the
      first fragility fracture and avoiding subsequent fractures in patients who
      already have an existing fracture. There are evidences from randomized controlled
      trials (RCTs) about the efficacy of antiresorptives, such as bisphosphonates in
      reducing the risk of fracture, but none of these agents completely abolish the
      fracture risk. The reduction of RRR by different therapies in RCTs is relatively
      constant but it is important to note that the proportion of inadequate-responders
      (i.e.: patients fracturing despite adequate pharmacological treatment) is
      increasing with the severity of the disease: the higher the risk of fracture the
      higher the proportion of inadequate-responders. Thus, the proportion of non
      responders across different trials is directly related to the fracture incidence
      observed in the control group of RCTs which is the most proximate indicator of
      osteoporosis severity.Teriparatide (TPTD) demonstrate a real increases of both
      trabecular and cortical bone volume, which are associated with a true reduction
      of fracture risk, as many RCTs confirm. The beneficial effect of introducing a
      treatment with antiresorptives after the treatment course with TPTD has been
      clearly demonstrated with the prevention of the reabsorption of the new bone
      tissue built during TPTD therapy and rapidly lowers cortical porosity, which
      leads to further increases in BMD. For these results, the introduction of an anti
      resorptive after the treatment course with TPTD is strongly recommended and taken
      into account.In Italy TPTD is fully reimbursed in patients incurring in a new
      vertebral or hip fracture while on chronic treatment with antiresorptive or in
      naive patients with 3 or more vertebral or hip fractures. In conclusion, since
      patients with severe osteoporosis are at very high risk of new fractures with
      worsening of quality of life and life expectancy, antiresorptives represent a sub
      optimal treatment in these patients, werehas, since TPTD demonstrated real and
      substantial improvements in bone mass and reduction of fracture risk
      independently of initial risk, TPTD represents the only therapeutic option able
      to reverse at least in part this disabling disease.

PMID- 22460016
TI  - Evaluation with stabilometric platform of balance disorders in osteoporosis
      patients. A proposal for a diagnostic protocol.
AB  - Osteoporosis is a systemic disease with reduced bone mass and qualitative
      alterations of the bone, associated to increased risk of fracture. Pathogenesis
      of osteoporosis fractures is multifactorial. Main risk factor is falls (except
      for vertebral fragility fractures which occurs often in absence of trauma). Aging
      by itself produces physiological changes: muscular hypotrophy with asthenia,
      deficit of visus and hearing together with associated pathologies and multi-drug
      therapies. In osteoporosis patients with vertebral fractures posture change
      occurs which reduces balance. After clinical postural evaluation it is possible
      to carry out instrumental evaluation of posture with computerized methods such as
      stabilometry, baropodometry, dynanometry and gait analysis. Examination carried
      out with use of stabilometric computerized platform allows stabilometric (body
      sway assessment) as well as posturometric examination (center of pressure
      assessment during quiet standing). Fundamental parameters obtained are: position
      of the body center of gravity, area and shape of sway density curve and velocity
      variables. Protocol of evaluation includes assessment of examination in standard
      condition and in condition of temporary sensorial deprivation (to investigate the
      influence of various afferent systems on the maintenance of posture and balance).
      Accurate evaluation of postural control in osteoporosis patients constitutes a
      fundamental tool in fracture risk evaluation due to fall and in identification
      and correction of modifiable factors responsible for balance defect. This
      approach, together with adequate drug therapy, may lead to significant reduction
      of fractures in osteoporosis patients with subsequent reduction of
      hospitalization and residual consequent disabilities.

PMID- 22460017
TI  - Risk of fractures and bone abnormalities in postmenopausal women with type 2
      diabetes mellitus.
AB  - Patients with diabetes mellitus (DM) are at high risk for fractures. However, the
      relationship between diabetes and osteoporosis is not yet completely understood.
      Many factors such as type of diabetes, type of population and co-morbidities may
      influence the type and severity of bone abnormalities in these patients. The aim
      of this study was to evaluate which factors may explain the risk of fractures in
      a homogeneous population of postmenopausal women with type 2 DM. Twenty-one
      consecutive postmenopausal women with type 2 DM were enrolled. Serum and urinary
      markers of bone metabolism as well as the biochemical markers of glucose
      homeostasis and diabetes severity were evaluated. Bone mineral density and
      prevalence of vertebral fractures were evaluated by using MOC DXA and spine
      radiography, respectively. The measurement of 25-hydroxyvitamin D serum levels
      revealed a condition of deficiency in 67% and insufficiency in 28% of patients.
      Vertebral and femoral neck T-scores were -1.1+/-1.1 and -0.8+/-1.0, respectively,
      while Z-scores were 0.1+/-1.1 and 0.1+/-0.9, respectively. Twenty-four % of
      patients showed >=1 vertebral fractures. There was a direct correlation between
      occurrence of fractures and PTH levels (p<0.05), and an inverse correlation
      between fractures and deficiency of 25-hydroxyvitamin D (p<0.05). In conclusion,
      although bone mineral density is comparable with that of age-matched normal
      subjects, patients with type 2 DM have an increased risk of fracture which
      appears to be associated with vitamin D deficiency and secondary increase of PTH.

PMID- 22460018
TI  - The importance of mechanics in the pathogenesis of fragility fractures of the
      femur and vertebrae.
AB  - This review highlights the role played by mechanical imbalances in the
      pathogenesis of fragility fractures of the femur and vertebrae. Particular
      attention is paid to vertebral fractures, and the consequences arising from
      mechanical imbalances are analyzed and evaluated to determine how much they
      contribute to worsening vertebral deformity and creating a domino effect.

PMID- 22460019
TI  - Bone mineral density of the proximal femur recovers after metal-on-metal hip
      resurfacing.
AB  - Bone resorption of the proximal femur is a frequent complication of total hip
      replacement. As hip resurfacing (HR) may load the bone more physiologically, we
      measured proximal femur bone mineral density (BMD) in 21 patients with HR. DEXA
      analysis was performed in the 7 Gruen zones and in the femoral neck pre
      operatively and at 3, 9, and 24-months post-operatively. In Gruen zone-2 the BMD
      ratio decreased to 90+/-18.8% (p=0.0009) at 3-months and completely restored at
      24-months to 100+/-17.7% (p=0.01). In Gruen zone-7 the BMD ratio decreased to
      93+/-15.3% (p=0.05) by 3 months and surpassed the baseline to 105+/-14.8%
      (p=0.01) at 24-months. A positive correlation was observed between valgus
      positioning of the femoral component and BMD in Gruen zone-2 and 7 respectively.
      HR preserves the bone-stock of the proximal femur. When the femoral component is
      implanted in a valgus position BMD is further enhanced, thus potentially reducing
      the risk of femoral neck fractures.

PMID- 22460020
TI  - Pharmacological treatment of hip fractured patients in Italy: a simulation based
      on Tuscany regional database for the TARGET project.
AB  - BACKGROUND: Italy is the Country with the highest life expectancy in the world,
      and over 75,000 elderly people experience a hip fracture each year. OBJECTIVE:
      following the Tuscany TARGET protocol, we aimed to estimate the costs of
      pharmacological treatment in the hypothesis of treating all elderly Italian
      people with hip fractures. METHODS: we analyzed the Tuscany healthcare system
      databases at the beginning of the Tuscany TARGET project for the prevention of
      hip fractures in elderly patients, and the Italian national hospitalizations
      records and DRGs databases concerning hip fractures occurred between 2000 and
      2005. RESULTS: costs sustained for pharmacological treatments effective in
      reducing the risk of subsequent hip fractures all over Italy would account for
      17.5 million Euros, representing only 0.18% of the overall national
      pharmaceuticals expenditures, while the national healthcare service is currently
      spending more than 30% of the overall pharmaceuticals expenditures in providing
      cardiovascular-active drugs. CONCLUSIONS: The burden of hip fractures in the
      Italian elderly population is substantial and must be acknowledged as an
      important health problem. Specific preventive strategies, such as the Tuscany
      TARGET project should be implemented in all Italian regions.

PMID- 22460021
TI  - Giant cell tumor in a case of Paget's disease of bone: an aggressive benign tumor
      exhibiting a quick response to an innovative therapeutic agent.
AB  - Giant cell tumor of bone, also called osteoclastoma, is a rare skeletal
      complication of Paget's disease of bone. We here report a patient from Southern
      Italy who developed a GCT infiltrating the neighboring tissues. We will focus on
      either a review on this rare bone tumor, including some genetic aspects, or the
      current established therapies. Since this case has been published in
      International literature, here we report the updated clinical findings on it.
      Finally, we will describe the therapeutic outcomes of this unique complication of
      Paget's disease of bone as a rapid response to an innovative therapeutic agent.

PMID- 22460022
TI  - Concurrent highly pathogenic porcine reproductive and respiratory syndrome virus
      infection accelerates Haemophilus parasuis infection in conventional pigs.
AB  - This study was aimed at determining the effect of highly pathogenic porcine
      reproductive and respiratory syndrome virus (HP-PRRSV) on Haemophilus parasuis
      (HPS) in co-infection. A quantitative real-time PCR targeting infB gene, which is
      conserved among different HPS serotypes, was developed to improve the accuracy
      and speed of the detection of HPS. A total of 32 four-week-old conventional pigs
      were distributed randomly into four groups: pigs in group I were intranasally
      infected with HP-PRRSV first, and were then intraperitoneally inoculated with HPS
      on 5 days after HP-PRRSV infection; pigs in group II were intranasally inoculated
      with HP-PRRSV alone; pigs in group III were intraperitoneally inoculated with HPS
      alone; pigs in group IV were intraperitoneally inoculated with physiological
      saline. The amount of HPS in serum on 0, 3, 6, 9 and 12 days post-inoculation
      (dpi) with HPS were detected using the established quantitative real-time PCR.
      Clinical signs, pathological changes and histopathological lesions were observed.
      The amount of HPS in serum reached 10(6)copies/MUl at 3 dpi with HPS in pigs of
      group I, while it arrived 10(5.7)copies/MUl at 9 dpi with HPS in pigs of group
      III. The HPS loads in hearts and lungs were much higher than in other tissues.
      The study showed that HP-PRRSV was able to accelerate HPS infection and loads.

PMID- 22460023
TI  - The use of information technologies for knowledge sharing by secondary healthcare
      organisations in New Zealand.
AB  - PURPOSE: To explore the extent of use of information technologies (ITs) for
      knowledge sharing by secondary healthcare organisations in New Zealand. METHODS:
      We used a self-administered questionnaire to survey Chief Information Officers at
      all 21 of New Zealand's District Health Boards regarding the extent to which
      their organisations use knowledge sharing activities involving ITs. The list of
      activities to include in the questionnaire was compiled by reviewing the
      literature. We analysed the extent of use of the knowledge sharing activities
      using descriptive statistics, repeated measures ANOVA, and correlation analysis.
      RESULTS: The response rate was 76%. Although all the responding organisations
      reported using ITs to share knowledge, they used ITs to share documents
      significantly more than to support discussions or to connect employees to
      experts. Discussions via teleconferencing, videoconferencing, and email lists
      were significantly more common than discussions via social media technologies:
      electronic discussion forums, blogs, and on-line chatrooms. There were
      significant positive correlations between publishing and accessing documents,
      between using teleconferencing and using videoconferencing, and between
      publishing and finding contact details of experts. CONCLUSION: New Zealand's
      District Health Boards are using a range of ITs to share knowledge. Knowledge
      sharing activities emphasising the sharing of explicit knowledge (via exchanging
      documents in electronic form) are significantly more common than knowledge
      sharing activities emphasising the sharing of tacit knowledge (via technology
      mediated discussions and via using technology to connect employees to experts).
      In view of the evidence in the literature that information technology may be
      highly effective in supporting tacit knowledge exchanges, our results suggest
      that health organisations should consider greater adoption of ITs for sharing
      tacit knowledge. The finding that several organisations are currently making
      extensive use of teleconferencing and videoconferencing facilities and expertise
      databases suggests that these technologies are useful and could be of benefit to
      other healthcare providers and that barriers to their adoption can be overcome.
      In order to facilitate the wider adoption of technologies, early adopters of both
      relatively established technologies and of the emerging technologies such as
      social media should be encouraged to publish accounts of their experiences of
      success and lessons learnt from any failures so that the knowledge gained is
      disseminated to the wider medical informatics community.

PMID- 22460024
TI  - Synthesis of [Tyr-5-Psi(CH2NMe)-Tyr-6]RA-VII, a reduced peptide bond analogue of
      RA-VII, an antitumor bicyclic hexapeptide.
AB  - A reduced peptide bond analogue of RA-VII, [Tyr-5-Psi(CH(2)NMe)-Tyr-6]RA-VII (3),
      was designed and synthesized. The key reduced cycloisodityrosine unit was
      prepared by reduction of the cycloisodityrosine derived from natural RA-VII,
      followed by connection with the tetrapeptide segment to afford a hexapeptide.
      Subsequent macrocyclization of the hexapeptide with FDPP under dilute conditions
      gave 3. Analogue 3 showed cytotoxic activity against P-388 cells, but its
      activity was much weaker than that of parent peptide RA-VII.

PMID- 22460025
TI  - The chemical synthesis of metabolically stabilized 2-OMe-LPA analogues and
      preliminary studies of their inhibitory activity toward autotaxin.
AB  - The chemical synthesis of five new metabolically stabilized 2-OMe-LPA analogues
      (1a-e) possessing different fatty acid residues has been performed by
      phosphorylation of corresponding 1-O-acyl-2-OMe-glycerols which were prepared by
      multistep process from racemic glycidol. The now analogues were subjected to
      biological characterization as autotaxin inhibitors using the FRET-based,
      synthetic ATX substrate FS-3. Among tested compounds 1-O-oleoyl-2-OMe-LPA (1e)
      appeared to be the most potent, showing ATX inhibitory activity similar to that
      of unmodified 1-O-oleoyl-LPA. Parallel testing showed, that similar trend was
      also observed for corresponding 1-O-acyl-2-OMe-phosphorothioates (2a-e,
      synthesized as described by us previously). 1-O-oleoyl-2-OMe-LPA (1e) was found
      to be resistant toward alkaline phosphatase as opposed to unmodified 1-O-oleoyl
      LPA.

PMID- 22460026
TI  - Synthesis of new opioid derivatives with a propellane skeleton and their
      pharmacology. Part 2: Propellane derivatives with an amide side chain.
AB  - We designed and synthesized propellane derivatives with a 6- or 7-amide side
      chain on the basis of the active conformation of the kappa selective agonist
      nalfurafine. The 6-amides showed high affinities for the kappa receptor, and one
      of the 6beta-amides showed higher kappa selectivity than nalfurafine. On the
      other hand, although the affinities of the 7-amides decreased compared to the 6
      amides, some 7alpha-amides showed the highest selectivities for the kappa
      receptor among the tested compounds. The affinities of 7beta-isomers were
      extremely low, which was postulated to result from the shielding effect of the
      7beta-amide side chain against the lone electron pair on the 17-nitrogen. This is
      the first conformational information about the 7-amide side chain in propellane
      derivatives.

PMID- 22460027
TI  - Double-stranded oligonucleotides containing 5-aminomethyl-2'-deoxyuridine form
      thermostable anti-parallel triplexes with single-stranded DNA or RNA.
AB  - This Letter describes the synthesis and properties of double-stranded antisense
      oligonucleotides connected with a pentaerythritol linker. We found that double
      stranded antisense oligonucleotides with aminomethyl residues have high affinity
      for single-stranded DNA or RNA in buffer solutions with and without MgCl(2).
      Thus, these oligonucleotides would be useful as antisense oligonucleotides for
      targeting single-stranded RNA through triplex formation.

PMID- 22460028
TI  - Design, synthesis, molecular docking and biological evaluation of new
      dithiocarbamates substituted benzimidazole and chalcones as possible
      chemotherapeutic agents.
AB  - A series of novel dithiocarbamates with benzimidazole and chalcone scaffold have
      been designed synthesised and evaluated for their antimitotic activity. Compounds
      4c and 9d display the most promising antimitotic activity with IC(50) of 1.66 MUM
      and 1.52 MUM respectively.

PMID- 22460029
TI  - Design, synthesis and structure-activity relationship of N-substituted tropane
      muscarinic acetylcholine receptor antagonists.
AB  - A novel series of N-substituted tropane derivatives was characterized as potent
      muscarinic acetylcholine receptor antagonists (mAChRs). Kinetic washout studies
      showed that the N-endosubstituted analog 24 displayed much slower reversibility
      at mAChRs than the methyl-substituted parent molecule darotropium. In addition,
      it was shown that this characteristic appeared to translate into enhanced which
      duration of action in a mouse model of bronchonstriction.

PMID- 22460030
TI  - New diarylureas and diarylamides possessing acet(benz)amidophenyl scaffold:
      design, synthesis, and antiproliferative activity against melanoma cell line.
AB  - A series of new diarylurea and diarylamide derivatives possessing
      acet(benz)amidophenyl scaffold was synthesized. Their in vitro antiproliferative
      activity was tested against A375P human melanoma cell line. Compounds 1c,d and
      2c,d showed the highest potencies with IC(50) values in sub-micromolar scale. In
      addition, compounds 1b,e,l and 2e,l were more potent than Sorafenib but with
      IC(50) values in micromolar range. Moreover, compound 2c was equipotent to
      Vemurafenib, and 2d showed higher potency than Vemurafenib against A375P. Molar
      refractometry calculation and ADME profiling of the highest potent four
      derivatives 1c,d and 2c,d are also reported.

PMID- 22460031
TI  - Quantitative structure and bioactivity relationship study on human
      acetylcholinesterase inhibitors.
AB  - Several QSAR (Quantitative Structure-Activity Relationships) models for
      predicting the inhibitory activity of 404 Acetylcholinesterase inhibitors were
      developed. The whole dataset was split into a training set and a test set
      randomly or using a Kohonen's self-organizing map. Then the inhibitory activity
      of 404 Acetylcholinesterase inhibitors was predicted using Multilinear Regression
      (MLR) analysis and Support Vector Machine (SVM) methods, respectively. For the
      test sets, correlation coefficients of all our models over 0.90 were achieved. Y
      randomization test was employed to ensure the robustness of our models and a
      docking simulation was used to confirm the descriptors we used.

PMID- 22460032
TI  - Development of hydrocortisone succinic acid/and 5-fluorouracil/chitosan
      microcapsules for oral and topical drug deliveries.
AB  - Recently, we demonstrated the safety use of calendula oil/chitosan microcapsules
      as a carrier for both oral and topical deliveries. We also reported the improved
      biological activity towards skin cells and Staphylococcus aureus of phyllanthin
      containing chitosan microcapsules. However, the possibility of both oral and
      topical applications was still necessary to be further studied. Here we
      investigated that both oral and topical applications of chitosan-based
      microcapsules were tested using hydrocortisone succinic acid (HSA) and 5
      fluorouracil (5-FU), respectively. The drug loading efficiency, particle size,
      surface morphology and chemical compositions of both drug loaded microcapsules
      were confirmed by UV-vis spectrophotometer, particle size analyzer, scanning
      electron microscope and Fourier transform infrared spectroscopy. The in vitro
      release studies revealed that both HSA and 5-FU could be released form chitosan
      microcapsules. The mean adrenocorticotropic hormone concentration in HSA loaded
      microcapsule mice plasma was detected to be lower than that of water control. One
      hundred micrograms per milliliter of 5-FU containing microcapsules exhibited a
      stronger growth inhibition towards skin keratinocytes than that of free 5-FU. In
      vitro drug delivery model demonstrated the delivery of 5-FU from microcapsule
      treated textiles into nude mice skin. Further uses of the drug loaded
      microcapsules may provide an efficiency deliverable tool for both oral and
      topical applications.

PMID- 22460033
TI  - Novel potent dual inhibitors of CK2 and Pim kinases with antiproliferative
      activity against cancer cells.
AB  - A novel family of potent dual inhibitors of CK2 and the Pim kinases was
      discovered by modifying the scaffolds of tricyclic Pim inhibitors. Several
      analogs were active at single digit nanomolar IC(50) values against CK2 and the
      Pim isoforms Pim-1 and Pim-2. The molecules displayed antiproliferative activity
      in various cell phenotypes in the low micromolar and submicromolar range,
      providing an excellent starting point for further drug discovery optimization.

PMID- 22460034
TI  - Fluoride enhances the activity of fungicides that destabilize cell membranes.
AB  - Fluoride has long been known to inhibit bacterial and fungal cell growth most
      likely by blocking the functions of key metabolic enzymes. In this study, we
      demonstrate that antifungal compounds that disrupt cell membrane integrity
      exhibit improved ability to inhibit cell growth when used with millimolar
      concentrations of fluoride. Specifically, antifungal compounds of the polyene
      class and an antifungal peptide exhibit synergy with fluoride to inhibit the
      growth of various fungal species, including Candida albicans. Our results
      demonstrate that certain compounds can be found that increase the cellular uptake
      of fluoride, and provide new opportunities for creating antimicrobial compounds
      whose functions are enhanced when combined with otherwise sub-inhibitory
      concentrations of small ions.

PMID- 22460035
TI  - Inhibition of platelet adhesion by peptidomimetics mimicking the interactive beta
      hairpin of glycoprotein Ibalpha.
AB  - beta-Hairpin peptidomimetics mimicking the interaction sites of the platelet
      receptor glycoprotein (GP)Ibalpha with von Willebrand factor (vWF) were
      synthesised and evaluated for their ability to increase platelet velocity under
      high shear conditions and to inhibit shear-induced platelet aggregation. A cyclic
      and bridged dodecapeptide 2e containing a heterochiral diproline motif was
      identified as a lead compound for the generation of a novel class of potential
      antiplatelet agents.

PMID- 22460036
TI  - Irreversible visual sensing of humidity using a cholesteric liquid crystal.
AB  - Irreversible optical sensing of humidity by a doped cholesteric liquid crystal is
      achieved by using a thin film of nematic host E7 with a binaphthylorthosilicate
      ester as dopant (guest). The film changes its color from blue (to green to orange
      to red) to colorless when exposed to humidity as the dopant is hydrolyzed.

PMID- 22460037
TI  - Measuring the value of public-private partnerships in the pharmaceutical
      sciences.

PMID- 22460038
TI  - A rapid label-free method for quantitation of human immunodeficiency virus type-1
      particles by nanospectroscopy.
AB  - Infection of cells with human immunodeficiency virus type-1 (HIV-1) results in
      the production of both infectious and non-infectious virions. At present, several
      assays are available for the quantitation of virus particles based on the
      presence of either viral capsid protein or nucleic acid. However, the ability to
      detect the total number of virus particles, both infectious and non-infectious,
      has been an elusive goal that would advance the study of virus assembly and
      egress. A rapid optical detection scheme for real-time label-free quantitation of
      HIV-1 virus particles was developed. Virions produced in cell cultures
      transfected transiently were evaluated with a nanospectroscopic assay.
      Quantitation with the optical detection scheme correlated with routine
      conventional assays. Nanospectroscopy can be used for the detection of both
      infectious and non-infectious, wild type and mutant strains of HIV-1 in solution
      at concentrations as low as 7*10(10)particles/ml, requiring volumes as small as 2
      MUl per assay, and in significantly less time than standard techniques. This
      assay provides a rapid, reliable system for quantifying virus particles in
      solution and could be applied to the study of viral particle production in cell
      culture.

PMID- 22460039
TI  - Prokaryote expression of HPeV-1 VP1 protein, production of VP1 polyclonal
      antibody and the development of an ELISA.
AB  - The VP1 protein of human parechovirus (HPeV) plays a critical role in receptor
      binding based on its functional arginine-glycine-aspartic acid (RGD) motif
      region. Currently, only the neutralisation assay is used for seroepidemiological
      surveys of HPeVs. In the present study, the VP1 gene of HPeV-1 was cloned into
      the vector pET28a(+) to express the His-tagged VP1 protein in the bacterium
      Escherichia coli Rosetta. The recombinant protein was purified from inclusion
      bodies by Ni(+)-NTA affinity chromatography under denaturing conditions, followed
      by a refolding process in gradient urea. The identity and antigenicity of the His
      tagged protein was confirmed by Western blotting using an anti-His monoclonal
      antibody and human HPeV-1-positive serum respectively. Polyclonal antibodies
      against the His-tagged VP1 protein were raised in rabbits by standard procedures,
      and the reactivity and specificity were tested by enzyme-linked immunosorbent
      assay (ELISA) and Western blot analysis. An indirect ELISA was developed based on
      the fusion protein VP1, and evaluated in order to facilitate the detection of
      antibodies in persons who had been infected naturally with HPeVs. A serological
      survey was performed using the assay amongst children in the Shanghai region of
      China; the seropositivity rate was found to be about 73%.

PMID- 22460040
TI  - Effect of intravenous dopamine infusion on pituitary and thyroid function and on
      nephroprotection.
AB  - INTRODUCTION; Catecholamines, including dopamine, are used in cardiac intensive
      care. OBJECTIVES: The aim of the study was to assess the effect of intravenous
      dopamine infusion on the function of pituitary gland in patients with acute
      cardiac failure. We analyzed changes in the serum levels of thyroid-stimulating
      hormone (TSH) and adrenocorticotropic hormone (ACTH), as well as potential
      nephroprotection. PATIENTS AND METHODS: The study involved 29 patients with
      chronic decompensated heart failure (New York Heart Association class III/IV;
      mean age 77.4 +/- 13.3 years). Dopamine was administered intravenously in doses
      varying from 1 to 5 MUg/kg/min. Measurements of TSH, free triiodothyronine (FT3),
      free thyroxine (FT4), and ACTH were taken directly before dopamine infusion,
      after 12 hours of continuous infusion, and 12 hours after the 72-hour infusion
      was completed. RESULTS: Serum FT3 levels were significantly higher before
      dopamine infusion than at 12 hours post infusion (5.12 +/- 1.16 vs. 4.27 +/- 0.89
      pmol/l, P < 0.005). Serum FT4 levels before the infusion were significantly
      higher than after 12 hours of continuous infusion as well as after 12 hours post
      infusion (18.79 +/- 5.33 vs. 17.06 +/- 4.61 pmol/l, P < 0.05; 18.79 +/- 5.33 vs.
      16.26 +/- 4.53 pmol/l, P < 0.05, respectively). There were no statistically
      significant differences between serum TSH and ACTH levels or in creatinine
      clearance before, during, and 12 hours post infusion. CONCLUSIONS: Intravenous
      infusion of dopamine may downregulate endocrine thyroid function; however, it has
      no significant effect on the pituitary gland-derived TSH and ACTH. There was no
      significant nephroprotective effect of low-dose dopamine infusion in patients
      with chronic decompensated chronic heart failure.

PMID- 22460041
TI  - Novel pathway of iron-induced blood coagulation: implications for diabetes
      mellitus and its complications.
AB  - Fibrinogen (FBG) is a high-molecular-weight protein and precursor to the
      enzymatically formed fibrin. It has been recently discovered that FBG can be
      converted into an insoluble, fibrin-like polymer by a nonenzymatic action of
      hydroxyl radicals (HRs). These free radicals are generated due to the reaction
      between hydroxyl groups of water and trivalent ferric ions without the
      participation of any redox agent. The interaction between HRs and FBG occurs in a
      purified system, as well as in human plasma and in whole blood. Scanning electron
      microscopy (SEM) of thrombin-induced fibers and those generated with ferric
      chloride has shown substantial differences in their morphology and susceptibility
      to enzymatic degradation. Fibrin strands caused by thrombin are thick and easily
      digested with chymotrypsin. By contrast, the dense matted deposits formed from
      FBG in the presence of ferric ions are remarkably resistant to proteolytic and
      chemical degradations due to the presence of intermolecular hydrophobic bonds.
      Thus, we postulate that this iron-catalyzed reaction represents a novel blood
      coagulation pathway operating in degenerative diseases. By means of SEM, we
      showed the presence of dense fibrin-like deposits in the blood of diabetic
      patients. Therefore, the prothrombotic state and cardiovascular complications
      observed in diabetes can be explained in terms of the persistent in vivo action
      of free iron. This phenomenon may explain hemorheologic disturbances in patients
      with metabolic syndrome and other diseases caused by iron overload. Of note, HRs
      can be effectively scavenged by phenolic substances; therefore, certain natural
      polyphenolic substances, which also scavenge HRs, may be considered to have a
      potential antidiabetic effect. Moreover, natural or synthetic iron-binding
      substances may also be considered as a new class of antidiabetic drugs.

PMID- 22460042
TI  - Do circulating antibodies against C1q reflect the activity of lupus nephritis?

PMID- 22460044
TI  - Solute-solvent interactions in cryosolutions: a study of halothane-ammonia
      complexes.
AB  - The formation of C-H...N bonded complexes of halothane with ammonia has been
      studied using infrared and Raman spectroscopy of solutions in the liquid rare
      gases argon, krypton and xenon, of supersonic jet expansions and of room
      temperature vapor phase mixtures. For the solutions and for the vapor phase
      experiments, the formation of complexes with 1:1 and 1:2 stoichiometry was
      observed. The complexation enthalpy for the 1:1 complex was determined to be -20
      (1) kJ mol(-1) in the vapor phase, -17.0 (5) kJ mol(-1) in liquid xenon and -17.3
      (6) kJ mol(-1) in liquid krypton. For the 1:2 complex in liquid xenon, the
      complexation enthalpy was determined to be -31.5 (12) kJ mol(-1). Using the
      complexation enthalpies for the vapor phase and for the solutions in liquid xenon
      and krypton, a critical assessment is made of the Monte Carlo Free Energy
      Perturbation approach to model solvent influences on the thermodynamical
      properties of the cryosolutions. The influences of temperature and solvent on the
      complexation shifts of the halothane C-H stretching mode are discussed.

PMID- 22460045
TI  - Deer as a potential wildlife reservoir for Parachlamydia species.
AB  - Wildlife populations represent an important reservoir for emerging pathogens and
      trans-boundary livestock diseases. However, detailed information relating to the
      occurrence of endemic pathogens such as those of the order Chlamydiales in such
      populations is lacking. During the hunting season of 2008, 863 samples (including
      blood, conjunctival swabs, internal organs and faeces) were collected in the
      Eastern Swiss Alps from 99 free-living red deer (Cervus elaphus) and 64 free
      living roe deer (Capreolus capreolus) and tested using ELISA, PCR and
      immunohistochemistry for members of the family Chlamydiaceae and the genus
      Parachlamydia. Parachlamydia spp. were detected in the conjunctival swabs, faeces
      and internal organs of both species of deer (2.4% positive, with a further 29.5%
      inconclusive). The very low occurrence of Chlamydiaceae (2.5%) was in line with
      serological data (0.7% seroprevalence for Chlamydia abortus). Further
      investigations are required to elucidate the zoonotic potential, pathogenicity,
      and distribution of Parachlamydia spp. in wild ruminants.

PMID- 22460046
TI  - Tissue-specific knockouts of ACAT2 reveal that intestinal depletion is sufficient
      to prevent diet-induced cholesterol accumulation in the liver and blood.
AB  - Acyl-CoA:cholesterol acyltransferase 2 (ACAT2) generates cholesterol esters (CE)
      for packaging into newly synthesized lipoproteins and thus is a major determinant
      of blood cholesterol levels. ACAT2 is expressed exclusively in the small
      intestine and liver, but the relative contributions of ACAT2 expression in these
      tissues to systemic cholesterol metabolism is unknown. We investigated whether CE
      derived from the intestine or liver would differentially affect hepatic and
      plasma cholesterol homeostasis. We generated liver-specific (ACAT2(L-/L-)) and
      intestine-specific (ACAT2(SI-/SI-)) ACAT2 knockout mice and studied dietary
      cholesterol-induced hepatic lipid accumulation and hypercholesterolemia. ACAT2(SI
      /SI-) mice, in contrast to ACAT2(L-/L-) mice, had blunted cholesterol absorption.
      However, specific deletion of ACAT2 in the intestine generated essentially a
      phenocopy of the conditional knockout of ACAT2 in the liver, with reduced levels
      of plasma very low-density lipoprotein and hepatic CE, yet hepatic-free
      cholesterol does not build up after high cholesterol intake. ACAT2(L-/L-) and
      ACAT2(SI-/SI-) mice were equally protected from diet-induced hepatic CE
      accumulation and hypercholesterolemia. These results suggest that inhibition of
      intestinal or hepatic ACAT2 improves atherogenic hyperlipidemia and limits
      hepatic CE accumulation in mice and that depletion of intestinal ACAT2 is
      sufficient for most of the beneficial effects on cholesterol metabolism.
      Inhibitors of ACAT2 targeting either tissue likely would be beneficial for
      atheroprotection.

PMID- 22460047
TI  - Non-linear association between ankle-brachial pressure index and prevalence of
      silent cerebral infarction in Japanese patients with type 2 diabetes.
AB  - OBJECTIVE: Patients with peripheral artery disease (PAD), defined as having low
      ankle-brachial pressure index (ABI), have increased risk for incident stroke
      compared with those without PAD. We aimed to reveal whether ABI abnormality,
      especially high ABI is associated with prevalent silent cerebral infarction (SCI)
      in type 2 diabetic patients. METHODS: We studied 538 Japanese type 2 diabetic
      patients, 227 women and 311 men, with a mean [+/-SD] age of 64+/-11 years. All
      patients underwent cranial magnetic resonance imaging (MRI). Values of ABI were
      classified as low (<0.9), normal (0.9<= and <1.3), and high (1.3<=). Logistic
      regression model was used to calculate odds ratio and 95% confidence interval
      (95% CI) for prevalent SCI. RESULTS: The mean ABI among the overall 538 patients
      was 1.09+/-0.16. Low and high ABI values were found in 52 (9.7%) and 33 (6.1%)
      patients, respectively. SCI was detected in 297 (55.2%) patients. The prevalence
      in patients with low, normal, and high ABI values were 88.5%, 49.7%, and 78.8
      (p<0.001), respectively. In the multivariate logistic regression analysis, both
      patients with high and low ABI were significantly increased risk of prevalent SCI
      (odds ratio 4.53, 95% CI 1.67-12.34, p=0.003 and odds ratio 3.50, 95% CI 1.50
      10.29, p=0.005), independently of other traditional cardiovascular risk factors,
      than those with normal ABI. CONCLUSIONS: Both high and low ABI may be strongly
      associated with prevalent SCI in Japanese patients with type 2 diabetes.

PMID- 22460048
TI  - Different prognostic value of white blood cell subtypes in patients with acute
      cerebral infarction.
AB  - OBJECTIVE: We aimed to investigate the relationship of each white blood cells
      (WBC) subtype with neurologic severity and outcome in acute stroke. METHODS: We
      included 779 patients with first-ever acute cerebral infarction within 72 h after
      symptom onset. We investigated the association between counts for WBC subtypes in
      peripheral blood at admission and (1) initial stroke severity; (2) early change
      in stroke severity within one week; and (3) functional outcome at three months.
      RESULTS: Higher total WBC and neutrophil counts were associated with more severe
      stroke at admission (p<0.001). In contrast, lower lymphocyte counts were
      associated with a lesser improvement during the first week after admission
      (p<0.05) and with poor functional outcome at three months (OR=0.706 per 1000
      lymphocyte counts/mm(3), p=0.020). CONCLUSIONS: Our study merits further
      investigation on the role of each WBC subtype in ischemic injury and different
      prognostic value of WBC subtypes measured at admission in acute stroke.

PMID- 22460049
TI  - The role of endoglin in atherosclerosis.
AB  - Endoglin (CD 105, TGF-beta receptor III) is a homodimeric transmembrane
      glycoprotein that plays a regulatory role in TGF-beta signaling. Its functional
      role in the context of atherosclerosis has yet to be defined and should be stated
      here. Therefore, we focused on the role of endoglin in atherosclerosis in both
      humans and experimental animals. Endoglin expression was demonstrated in
      atherosclerotic vessels predominantly in endothelial cells and smooth muscle
      cells in various types of blood vessels in mice and humans, suggesting its
      participation in atherogenesis. Endoglin expression was also related to the
      expression of eNOS in endothelium, repair of the vessel wall, plaque
      neoangiogenesis, production of collagen and stabilization of atherosclerotic
      lesions. In addition, increased levels of soluble endoglin were associated with
      hypercholesterolemia, atherosclerosis, acute myocardial infarction and were
      related to inhibition of TGF-beta signaling in the vessel wall. Moreover, soluble
      endoglin levels were significantly lowered after a series of extracorporeal
      eliminations in patients with familial hypercholesterolemia. Additionally, statin
      treatment decreased levels of soluble endoglin and increased its expression in
      aorta, which was related to reduced atherosclerosis in mice. In conclusion, we
      propose that measurement of soluble endoglin might give information about
      progression of the atherosclerotic process or the efficacy of therapeutic
      interventions, which is the task that must be answered in clinical trials.

PMID- 22460050
TI  - Chronic inflammation, albuminuria, and functional disability in older adults with
      cardiovascular disease: the National Health and Nutrition Examination Survey,
      1999-2008.
AB  - OBJECTIVE: Although C-reactive protein (CRP) and albuminuria are well-documented
      cardiovascular risk markers, the functional implications of these biomarkers and
      their combination on functional disability and metabolic risks in patients with
      cardiovascular disease (CVD) are unknown. METHODS: Data were from 1403 adults
      (>=60 years, mean 73.2 years) with CVD, ascertained by self-reported diagnosis of
      angina, coronary heart disease, congestive heart failure, myocardial infarction
      or stroke, in the National Health and Nutrition Examination Survey 1999-2008.
      Disability in activities of daily living (ADL), instrumental activities of daily
      living (IADL), leisure and social activities (LSA), general physical activities
      (GPA), and lower-extremity mobility (LEM) were obtained from self-reports. The
      urinary albumin-to-creatinine ratio (UACR) was calculated by dividing the urinary
      albumin value by the urinary creatinine concentration. CRP levels were quantified
      by latex-enhanced nephelometry. RESULTS: Inflammation and albuminuria were
      associated with disability. In the full-adjusted models, odds ratios (ORs) (95%
      confidence intervals [CIs]) of disability in ADL, LSA, and LEM were 1.60 (1.13
      2.28), 1.76 (1.22-2.55) and 2.31 (1.62-3.31), respectively, comparing
      participants in the highest CRP quartile to the lowest (p values for trend across
      CRP quartiles<0.01). The corresponding ORs (95% CI) for disability in ADL, IADL,
      LSA, and LEM were 1.71 (1.20-2.45), 1.72 (1.21-2.45), 1.46 (1.01-2.12) and 2.50
      (1.73-3.62), respectively, comparing participants in the highest UACR quartile to
      the lowest. We found combined association of inflammation and albuminuria with
      disability and with metabolic risks. Based on medians of both UACR and CRP,
      subjects with both higher levels of both markers had higher odds of disability
      and a more unfavorable metabolic profile than those with lower levels.
      CONCLUSIONS: Elevated levels of CRP and UACR independently correlate with
      disability among older adults with CVD. There is a combined association of
      inflammation and albuminuria on multiple domains of disability and metabolic
      risks, suggesting the presence of elevated UACR may amplify the association of
      inflammation with disability and with metabolic risk in older adults living with
      CVD.

PMID- 22460052
TI  - Can computed tomographic gastrography and multiplanar reformatting aid the
      laparoscopic surgeon in planning a gastric resection? A pictorial essay.
AB  - PURPOSE: To assess the value and feasibility of computed tomographic gastrography
      and multiplanar reformatting in the preoperative evaluation of patients
      undergoing laparoscopic gastric resection. MATERIALS AND METHODS: Fourteen
      patients with gastric lesions were included in the study. A supine scan was
      performed after a hypotonic drug, an effervescent agent, and intravenous
      contrast. This was followed by delayed prone and decubitus scans. We created
      multiplanar reformats, transparency rendered images, and endoluminal images. The
      tumours were localized, and distances were measured to the esophagogastric
      junction and the pylorus. RESULTS: Eleven patients underwent resections. Seven
      had laparoscopic wedge resections for aberrant pancreas (1 patient), carcinoid
      (1), Castleman disease (1), and gastrointestinal stromal tumours (GISTs) (4). One
      patient had an open subtotal gastrectomy for carcinoma due to adhesions. One had
      a hand-assisted sleeve resection for a gastrointestinal stromal tumour. Two had
      hand-assisted total gastrectomies for carcinoma and a GIST. For surgical
      planning, the surgeon rated the imaging extremely useful in 7 and useful in 4.
      Imaging was extremely useful or useful to localize laparoscopically invisible
      tumours in 6 patients and to relate tumours to the esophagogastric junction or
      pylorus and to assess localized vs extensive resection in 8. Correlation was
      excellent between the preoperative imaging and the intraoperative findings.
      CONCLUSIONS: Computed tomographic gastrography and multiplanar reformatting are
      useful aids in preoperative planning of laparoscopic gastric resections.

PMID- 22460051
TI  - Detection of subclinical atherosclerosis in familial hypercholesterolemia using
      non-invasive imaging modalities.
AB  - OBJECTIVES: To investigate the extent of subclinical atherosclerosis in
      asymptomatic familial hypercholesterolemia (FH) patients using non-invasive
      images techniques. PATIENTS, METHODS AND RESULTS: The atherosclerotic burden of
      36 molecularly defined FH patients (18 males, 45.7+/-10.9 years) without evidence
      of cardiovascular disease receiving lipid-lowering treatment and 19 (47.8+/-11.3
      years) controls was investigated. Descending thoracic aorta magnetic resonance
      imaging (MRI) was performed in a 1.5 T equipment with T1 and T2 sequences to
      characterize atherosclerotic plaques and to measure aortic wall volumen. Carotid
      intima-media thickness (cIMT) and presence of plaques were measured using B-mode
      carotid ultrasound. Mean aortic wall volumen, cIMT and atherosclerotic plaques in
      aorta were significantly higher in FH cases (P<0.001). A significant correlation
      between aortic wall volume and cIMT was observed (P<0.01). Aortic MRI detected
      plaques in 94% and carotid ultrasound in 14% of cases. Lipid-rich plaques were
      observed only in FH cases (33%) and were associated with family history of
      premature coronary artery disease (P<0.05). CONCLUSIONS: Asymptomatic middle-aged
      FH patients have significantly higher atherosclerotic burden than controls. cIMT
      has shown a significant correlation with aortic wall volume and MRI allowed the
      detection of lipid-rich plaques in FH subjects that were associated with family
      history of premature coronary artery disease.

PMID- 22460054
TI  - Development and validity data of the Brazilian Internet Study on Temperament and
      Psychopathology (BRAINSTEP).
AB  - BACKGROUND: The internet provides a research opportunity for psychiatry and
      psychology. This article presents the development and preliminary data of a large
      web-survey created to study how temperament relates to other psychological
      measures, behavior and psychiatric disorders. METHODS: We used the Affective and
      Emotional Composite Temperament Scale (AFECTS) to evaluate temperament and we
      selected several self-report instruments to evaluate behavior, psychological
      constructs and mental disorders. The system provides anonymous psychological
      (phase 1) and psychiatric (phase 2) feedback and includes questions to assess the
      validity of the answers. Each phase has around 450 questions. This system was
      broadcast utilizing Brazilian media. RESULTS: After the exclusion of 21.5% of the
      volunteers (those who failed the validation questions), 41,427 participants
      concluded the first part of the system (mean age=31.2+/-10.5 yrs, 26.9% males),
      and 21,836 (mean age=32.5+/-10.9 yrs, 25.1% males) completed phase 2. Around 25%
      have received a psychiatric diagnosis from a mental health professional.
      Demographic and temperament profiles of those who completed either only 80
      questions, only phase 1, or the whole system were similar. The rate of non
      serious answers (e.g. on bizarre behaviors) was very low and congruency of
      answers was very high. The internal consistency of classical trait scales (TCI-R
      and PANAS) was high (Cronbach's alpha>0.80) for all dimensions. LIMITATIONS:
      Relatively high dropout rate due to the length of the process and an
      overrepresentation of female, young and well-educated subjects. CONCLUSIONS: The
      BRAINSTEP provides valid and abundant data on psychological and psychiatric
      measures.

PMID- 22460055
TI  - Medical costs and vasculometabolic comorbidities among patients with bipolar
      disorder in Taiwan - a population-based and matched-control study.
AB  - BACKGROUND: Bipolar disorder (BD) is a costly disease with a high rate of
      vasculometabolic comorbidities. The aims of this study were to explore the 1-year
      treatment cost, including total medical and non-psychiatric services, and the
      prevalence of vasculometabolic comorbidities in individuals with BD. METHODS: A
      nationwide population-based dataset, covering the years 2006 and 2007, was
      obtained from the Taiwan National Health Insurance claims database. The study
      sample comprised patients discharged from hospitals between 1 January 2006 and 31
      December 2007. Annual non-psychiatric and total medical costs and
      vasculometabolic comorbidities were examined. Generalized linear models were used
      to examine the medical costs, and conditional logistic regression analyses were
      carried out to test the prevalence of vasculometabolic comorbidities in people
      with BD and to compare this with that found in matched controls. RESULTS: The
      total medical cost was 11-fold higher (New Taiwan [NT] $227,040 vs. NT$20,461),
      and the non-psychiatric medical cost was 1.7-fold higher (NT$33,173 vs.
      NT$19,406) with regard to the individuals with BD vs. the matched controls. The
      prevalence of vasculometabolic comorbidities was significantly higher in the
      individuals with BD than in the controls (ratio ranging from 1.86 to 4.06).
      CONCLUSIONS: Both the non-psychiatric healthcare utilization and the prevalence
      of vasculometabolic comorbidities are higher with regard to individuals with BD
      vs. their matched controls. Therefore, treatment of BD should integrate medical
      and psychiatric care to decrease the impact of medical comorbidities, which may
      also decrease the overall medical cost.

PMID- 22460056
TI  - Disrupted resting-state functional connectivity of the hippocampus in medication
      naive patients with major depressive disorder.
AB  - BACKGROUND: The hippocampus has been reported to exhibit structural and
      functional alterations in patients with major depressive disorder (MDD). But
      functional relationships between this area and other regions remain unclear.
      METHODS: Region of interest-based correlation analyses were performed in the
      resting-state functional magnetic resonance imaging data to examine differences
      in functional connectivity (FC) of the hippocampus between medication-naive
      patients with MDD and healthy adults. Correlation analyses were done between
      clinical variables and the strength of FC in regions showing group differences.
      RESULTS: Positive FC with the hippocampal-ROIs was seen in bilateral limbic
      system, subcortical areas, temporal lobe, medial and inferior prefrontal cortex
      while negative FC was observed in bilateral prefrontal cortex, parietal and
      occipital cortex and the cerebellum. Group comparison showed impaired functional
      connections of the hippocampus in MDD, with a lack of negative FC in left
      hippocampal-ROI to bilateral middle frontal gyrus, as well as decreased negative
      FC in right hippocampal-ROI to right inferior parietal cortex and the cerebellum.
      Negative correlations were seen between illness duration and the strength of FC
      in the prefrontal and parietal cortex. LIMITATIONS: An optimized method taking
      individual variability of hippocampal volume into account is merited for the
      definition of seed regions and computation of FC. Further studies recruiting
      subjects with subthreshold depressive symptoms are needed. CONCLUSIONS: Abnormal
      functional relationships between the hippocampus and cortical areas may underlie
      the pathophysiology of MDD.

PMID- 22460057
TI  - Chemotherapy-induced nausea and vomiting in clinical practice: impact on
      patients' quality of life.
AB  - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) in cancer patients
      are common symptoms most feared by patients. The aim of this study was to analyze
      the impact of CINV associated to moderate/highly emetogenous chemotherapy
      regimens on patients' quality of life (QoL). PATIENTS AND METHODS: Open,
      multicenter, prospective observational study was performed. Each patient filled
      out a patient diary for each cycle from the day before chemotherapy and for the
      next 5 days that included the number of emetic episodes, the intensity of nausea,
      and QoL evaluation (functional living index-emesis questionnaire). RESULTS: Data
      from 202 consecutive patients from nine university hospitals were collected, but
      only data from 160 were analyzed (79.2 %). Most of the participants (70 %) were
      women with a mean age of 50 years (SD 1.2 years). The most frequent cancer site
      was breast (44 %) followed by lung (16 %) and 76.3 % were receiving highly
      emetogenous chemotherapy. Despite the use of antiemetic prophylaxis, patients
      experienced significant nausea and vomiting during 31 % (3.2 % during acute, 15.0
      % during delayed phase, and 13.2 % during both phases) and 45.1 % (5.1 % only
      during the acute phase, 23.5 % only during the delayed phase and 16.5 % during
      both phases) of the cycles, respectively, having 44.5 % (nausea) and 39.3 %
      (emesis) of the cycles an impact on patients' QoL. CONCLUSIONS: The results of
      the study confirm the detrimental effect of CINV on patients' QoL despite the use
      of antiemetic prophylaxis (5HT(3) receptor antagonist, steroids, and dopamine
      receptor antagonists). It is mandatory to intensify the detection of CINV in
      order to improve the management of these important, albeit frequent, side effects
      of cancer treatments.

PMID- 22460058
TI  - Breast cancer related lymphedema in patients with different loco-regional
      treatments.
AB  - INTRODUCTION: Lymphedema, a sequela of breast cancer and breast cancer therapy,
      changes functional abilities and may affect a patient's psychosocial adjustment
      and overall quality of life. Aim of this prospective observational study was to
      determine the rate of mid-term and late time period lymphedema in breast cancer
      patients with different loco-regional treatments, and factors associated with
      lymphedema. MATERIALS AND METHODS: Patients surgically treated for early-stage
      breast cancer were prospectively enrolled in the study. Demographic, clinical,
      pathological, and loco-regional treatments data of patients and lymphedema rates
      were recorded. Patients were divided into six groups regarding different loco
      regional treatments. Pre- and postoperative (12 months, and median 64 months
      after surgery) circumferences of arms were recorded. RESULTS: 218 patients, all
      female with a median age of 48 (19-82) years, were included in the study. The
      numbers of patients in breast conservation surgery group (BCS) (N=104),
      mastectomy group (N=114), sentinel lymph node biopsy group (SLNB) (N=80),
      axillary lymph node dissection group (ALND) (N=138), group with radiotherapy (RT)
      (N=88) and group without radiotherapy (N=130). Incidence of lymphedema after
      surgery in mid-term period was 24.8%. The rate of lymphedema at 64 months median
      follow-up time was 7.3%. (BCS: 11.1%, 4.2% and 0.5%; Mastectomy: 15.0%, 3.2% and
      1.4%; SLNB: 8.0%, 1.9% and 0.5%; ALND: 18.0%, 5.3% and 1.4%; RT: 14.7%, 6.3% and
      1.4%; without RT: 11.4%, 2.1% and 0.5%). When we excluded patients with both mid
      term and late term lymphedema, only four patients developed lymphedema at late
      time, then re-calculated late term lypmhedema rate was 1.8%. The factors
      affecting the lymphedema was ALND and radiotherapy (RT) and no lymphedema was
      detected in patients underwent breast conserving surgery and SLNB. Age and body
      mass index were not related to lymphedema at any time. CONCLUSION: The incidence
      of lymphedema gradually increased in time and a quarter of patients experienced
      the complication at the end of year. The rate of lymphedema in patients with ALND
      was significantly higher than patients with SLNB alone. If RT added to SLNB the
      lymphedema rate was getting higher than SLNB alone. In all patients lymphedema
      rate was decreased one year after the surgery and further decreased at median 64
      months follow-up time period.

PMID- 22460059
TI  - Development and validation of an intrinsic landmark-based gating protocol
      applicable for functional and molecular ultrasound imaging.
AB  - OBJECTIVES: To implement a retrospective intrinsic landmark-based (ILB) gating
      protocol for contrast-enhanced ultrasound (CEUS) and to compare its efficiency to
      non-gated, manually gated and extrinsically gated CEUS. METHODS: CEUS of the
      liver was performed in healthy mice (n = 5) and in NEMO knockout mice with
      dysplastic livers (n = 5). In healthy animals, first-pass kinetics of non
      specific microbubbles was recorded. Knockout mice were analysed regarding
      retention of VEGFR2-specific microbubbles. For retrospective gating, a landmark
      which showed respiratory movement was encircled as a region of interest (ROI).
      During inspiration, the signal intensity within the ROI altered, which served as
      gating signal. To evaluate the accuracy, non-gated, extrinsically gated and ILB
      gated time-intensity curves were created. For each curve, descriptive parameters
      were calculated and compared to the gold standard (manual frame-by-frame gating).
      RESULTS: No significant differences in the variation of ILB- and extrinsically
      gated time-intensity curves from the gold standard were observed. Non-gated data
      showed significantly higher variations. Also the variation of molecular
      ultrasound data was significantly lower for ILB-gated compared to non-gated data.
      CONCLUSION: ILB gating is a robust and easy method to improve data accuracy in
      functional and molecular ultrasound liver imaging. This technique can presumably
      be translated to contrast-enhanced ultrasound examinations in humans. KEY POINTS:
      * Quantitative analysis of the uptake of contrast agents during ultrasound is
      complex. * Intrinsic landmark-based gating (ILB) offers a simple implementable
      method for motion correction. * Results using ILB-gating are comparable to
      extrinsic gating using external biomonitoring devices. * Functional and molecular
      imaging of mobile organs will benefit from ILB gating.

PMID- 22460060
TI  - Progression of outflow tract obstruction in the fetus.
AB  - Fetal ventricular outflow tract obstruction (OTO) is congenital heart disease
      with significant potential for progression before birth as a consequence of the
      unique nature of the fetal circulation. The pattern of evolution depends upon the
      timing of development, severity of obstruction and the influence of the OTO on
      the fetal atrioventricular valve and myocardial function. Critical aortic (AS) or
      pulmonary (PS) valve stenosis, the two most common forms of fetal OTO, may be
      associated with progressive ventricular and great artery hypoplasia if presenting
      early in gestation or with normal ventricular and great artery growth if evolving
      later in gestation. In some affected fetuses, AS or PS may lead to the evolution
      of fetal heart failure. This article will review our current understanding of the
      natural history of fetal AS and PS, experience with fetal intervention and future
      directions of research.

PMID- 22460061
TI  - Parental psychological distress and anxiety after a successful IVF/ICSI procedure
      with and without preimplantation genetic screening: follow-up of a randomised
      controlled trial.
AB  - BACKGROUND: Infertility treatment has an acknowledged psychological impact on
      women and their partners; however, information about the development of parental
      well-being after child birth is inconclusive. Preimplantation genetic screening
      (PGS) has been suggested to increase the efficacy of infertility treatments, but
      the effect it may have on parental well-being is unknown. AIM: To evaluate
      parental distress and anxiety at one and two years after successful infertility
      treatment and to explore variables that might affect parental outcome, including
      PGS and child behaviour. STUDY DESIGN: Follow-up of a randomised controlled trial
      (RCT) on the efficacy of PGS. SUBJECTS: Parents (n=101) that successfully
      underwent IVF/ICSI with or without PGS. OUTCOME MEASURES: At one and two years,
      parental distress and anxiety were assessed with the General Health Questionnaire
      30 and State Trait Anxiety Inventory, respectively. At two years, child
      development and behaviour were assessed with the Dutch Bayley Scales of Infant
      Development-II and the Child Behaviour Checklist 11/2-5, respectively. RESULTS:
      PGS had no effect on parental distress or anxiety. Child behaviour problems were
      associated with parental distress and anxiety. There was a main effect of time on
      parental distress, with distress levels decreasing over time. CONCLUSIONS: We
      found no objection to PGS related to parental psychological distress and anxiety.
      When parental psychological problems are present after infertility treatment, the
      results of this study could be useful to support counselling.

PMID- 22460062
TI  - Changes in the dielectric properties of ex vivo bovine liver during microwave
      thermal ablation at 2.45 GHz.
AB  - In microwave thermal ablation (MTA) therapy, the dielectric properties of the
      target tissue play an important role in determining the radiation properties of
      the microwave ablation antenna. In this work, the ex vivo dielectric properties
      of bovine liver were experimentally characterized as a function of the
      temperature during MTA at the frequency of 2.45 GHz. The obtained data were
      compared with measurements performed at the end of the MTA treatment, and
      considering the heating achieved with a temperature-controlled water bath.
      Finally, measured data were used to perform a numerical study evaluating the
      effects of changes in tissue's dielectric properties during the MTA treatment on
      the radiation properties of a microwave interstitial ablation antenna, as well as
      on the obtained thermal lesion. Results evidenced a significant decrease of both
      relative permittivity (about 38%) and electric conductivity (about 33%) in the
      tissue during treatment as the temperature increased to over 60  degrees C, with
      a dramatic drop when the temperature approached 100  degrees C. Moreover, the
      numerical study evidenced that changes in tissue's dielectric properties during
      the MTA treatment affect the distribution of the power absorbed by the tissue
      (specific absorption rate-SAR, W kg(-1)) surrounding the microwave interstitial
      ablation antenna, leading to a peak SAR up to 20% lower, as well as to a thermal
      lesion up to 8% longer. This work may represent a preliminary step towards the
      future development of a procedure for MTA treatment planning.

PMID- 22460063
TI  - GABA system changes in methylphenidate sensitized female rats.
AB  - Methylphenidate (MPD) is a psychostimulant that is prescribed to treat attention
      deficit/hyperactivity disorder (ADHD) and has been used as a recreational drug.
      In animal models, repetitive exposure to methylphenidate can induce a behavioral
      sensitization. Stimulants are able to change neuronal circuits in the mesolimbic
      pathway, and the GABA system is one of the most involved neurotransmitter systems
      in this process. Women represent a risk group for psychostimulant abuse because
      they respond more strongly, which is probably due to the influence of sex
      hormones. The objective of the present study was to investigate the influence of
      sex hormones on behavioral sentsitization and changes to glutamic acid
      decarboxylase (GDA65 and GDA67) isoenzymes and alpha2 GABAA receptor subunit mRNA
      expression in the prefrontal cortex and the striatum of rats, as induced by
      methylphenidate administration (2.5 mg/kg, i.p.). Female rats were divided into 2
      hormonal conditions: ovariectomized and intact group. Repeated methylphenidate
      treatment led to behavioral sensitization, which was stronger in females with
      circulating hormones (intact group). The analysis of mRNA levels in the striatum,
      in both groups, showed a decline in GAD65, but not GAD67, transcription after
      repeated methylphenidate treatment. In the prefrontal cortex, both GAD65 and
      GAD67 showed an increase in transcription with repeated methylphenidate
      treatment. There was no change in the transcription level of alpha2 GABAA
      receptor subunits. In conclusion, it was shown that sex hormones were able to
      modify behavioral sensitization to methylphenidate and the drug affected the GABA
      system in brain areas known to be involved in the development of drug dependence.

PMID- 22460064
TI  - Inhibition of central angiotensin converting enzyme ameliorates scopolamine
      induced memory impairment in mice: role of cholinergic neurotransmission,
      cerebral blood flow and brain energy metabolism.
AB  - Evidences indicate that inhibition of central Renin angiotensin system (RAS)
      ameliorates memory impairment in animals and humans. Earlier we have reported
      involvement of central angiotensin converting enzyme (ACE) in streptozotocin
      induced neurodegeneration and memory impairment. The present study investigated
      the role of central ACE in cholinergic neurotransmission, brain energy metabolism
      and cerebral blood flow (CBF) in model of memory impairment induced by injection
      of scopolamine in mice. Perindopril (0.05 and 0.1 mg/kg, PO) was given orally for
      one week before administration of scopolamine (3mg/kg, IP). Then, memory function
      was evaluated by Morris water maze and passive avoidance tests. CBF was measured
      by laser Doppler flowmetry. Biochemical and molecular parameters were estimated
      after the completion of behavioral studies. Scopolamine caused impairment in
      memory which was associated with reduced CBF, acetylcholine (ACh) level and
      elevated acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level.
      Perindopril ameliorated scopolamine induced amnesia in both the behavioral
      paradigms. Further, perindopril prevented elevation of AChE and MDA level in mice
      brain. There was a significant increase in CBF and ACh level in perindopril
      treated mice. However, scopolamine had no significant effect on ATP level and
      mRNA expression of angiotensin receptors and ACE in cortex and hippocampus. But,
      perindopril significantly decreased ACE activity in brain without affecting its
      mRNA expression. The study clearly showed the interaction between ACE and
      cholinergic neurotransmission and beneficial effect of perindopril can be
      attributed to improvement in central cholinergic neurotransmission and CBF.

PMID- 22460065
TI  - Ventilation heterogeneity predicts asthma control in adults following inhaled
      corticosteroid dose titration.
AB  - BACKGROUND: Asthma guidelines recommend inhaled corticosteroid (ICS) dose
      titration for patients on the basis of an assessment of current asthma control.
      However, the physiological determinants of asthma symptom control are poorly
      understood and spirometry is a poor predictor of symptomatic response. OBJECTIVE:
      To determine the role of small airway measurements in predicting the symptom
      response following ICS dose titration. METHODS: Adult asthmatic patients had the
      Asthma Control Questionnaire (ACQ) scores and lung function measured at baseline
      and after 8 weeks. Tests included spirometry, plethysmography, sputum cell count,
      exhaled nitric oxide, airway hyperresponsiveness to mannitol, respiratory system
      mechanics using the forced oscillation technique, and ventilation heterogeneity
      using the multiple breath nitrogen washout. The parameters ventilation
      heterogeneity in convection-dependent airways and ventilation heterogeneity in
      diffusion-dependent airways were derived as measures of ventilation heterogeneity
      in the small airways. The dose of ICS was doubled if the ACQ score was greater
      than or equal to 1.5 (uptitration) and quartered if the ACQ score was less than
      1.5 (downtitration). The relationships between baseline physiological parameters
      and the change in the symptom-only 5-item ACQ (deltaACQ-5) were examined by using
      Spearman correlations, forward stepwise linear regressions, and receiver operator
      curve analyses. RESULTS: ICS dose uptitration (n= 20) improved ACQ-5 scores (1.76
      to 1.16; P= .04). Baseline fraction of exhaled nitric oxide (r= -0.55; P= .01)
      and ventilation heterogeneity in convection-dependent airways (r= -0.64; P= .002)
      correlated with deltaACQ-5, but ventilation heterogeneity in convection-dependent
      airways was the only independent predictor (r(2) = 0.34; P = 0.007). ICS dose
      downtitration (n= 41) worsened ACQ-5 scores (0.46 to 0.80; P< .001), with 29% of
      the patients having a deltaACQ-5 of greater than 0.5. Only baseline ventilation
      heterogeneity in diffusion-dependent airways correlated with deltaACQ-5 (r= 0.40;
      P= .009) and identified subjects with deltaACQ-5 of greater than 0.5 (receiver
      operator curve area under the curve= 0.78; P= .0003). CONCLUSIONS: Ventilation
      heterogeneity predicts symptomatic responses to ICS dose titration. Worse small
      airways function predicts symptomatic improvement to ICS dose uptitration and
      loss of symptom control during downtitration.

PMID- 22460066
TI  - Increased neutrophilia in nasal polyps reduces the response to oral
      corticosteroid therapy.
AB  - BACKGROUND: Nasal polyps (NPs) are characterized by eosinophilic inflammation,
      which is generally considered sensitive to corticosteroid treatment. OBJECTIVES:
      We evaluated levels of neutrophilia in NPs and investigated whether increased
      neutrophilia in polyp tissue affected the response to corticosteroid treatment.
      METHODS: We studied 3 independent cross-sectional groups of patients with NPs.
      Levels of infiltration by different types of inflammatory cells were determined
      by using immunohistochemical analyses and compared with those seen in control
      nasal tissues from subjects without NPs. Levels of inflammatory mediators were
      measured by using real-time PCR, ELISA, and FlowCytomix analyses. Patients with
      NPs received oral corticosteroid therapy (30 mg of prednisone once daily for 7
      days); clinical parameters of efficacy were associated with NP phenotypes.
      RESULTS: Among patients with NPs, 76.5% had an eosinophilic phenotype, 46.0% had
      a neutrophilic phenotype, and 35.8% had a mixed phenotype (indicated by double
      staining). Overall, patients' symptoms improved after corticosteroid treatment;
      numbers of eosinophils and levels of their mediators (IL-4 and IL-5), but not
      numbers of neutrophils or levels of their mediators (IL-8 and interferon
      inducible protein 10), were reduced (P< .05). After corticosteroid treatment,
      patients with the nonneutrophilic phenotype (neutrophil negative) had
      significantly greater reductions in bilateral polyp size scores, nasal congestion
      scores, total nasal symptom scores, and nasal resistance than patients with the
      neutrophilic phenotype (neutrophil positive, P< .05). CONCLUSIONS: There are
      different phenotypes of NPs based on the type of immune cell infiltrate and
      cytokines produced (eosinophilic or neutrophilic). Patients with the neutrophilic
      phenotype have less response to treatment with corticosteroids based on symptom
      scores.

PMID- 22460067
TI  - Ultrarush versus semirush initiation of insect venom immunotherapy: a randomized
      controlled trial.
AB  - BACKGROUND: Venom immunotherapy can be initiated by different schedules, but
      randomized comparisons have not been performed. OBJECTIVE: We aimed to compare
      the safety of 2 initiation schedules. METHODS: Patients of any age with prior
      immediate generalized reactions to jack jumper ant (Myrmecia pilosula) stings
      were randomized to venom immunotherapy initiation by a semirush schedule over 10
      visits (9 weeks) or an ultrarush schedule over 3 visits (2 weeks). In a
      concurrent treatment efficacy study, the target maintenance dose was randomized
      to either 50 MUg or 100 MUg. The primary outcome was the occurrence of 1 or more
      objective systemic reactions during venom immunotherapy initiation. Analyses were
      by intention to treat. We also assessed outcomes in patients who declined
      randomization. RESULTS: Of 213 eligible patients, 93 were randomized to semirush
      (44 patients) or ultrarush (49 patients) initiation. Objective systemic reactions
      were more likely during ultrarush initiation (65% vs 29%; P < .001), as were
      severe reactions (12% vs 0%; P= .029). Times to maximal increases in venom
      specific IgG(4) were no different between treatments, whereas the maximal
      increase in venom-specific IgE occurred earlier with ultrarush treatment. Similar
      differences between methods were observed in patients who declined randomization.
      One hundred seventy-eight patients were randomized to maintenance doses of either
      50 MUg (90 patients) or 100 MUg (88 patients). The target maintenance dose had no
      effect on the primary outcome, but multiple-failure-per-subject analysis found
      that the 50 MUg dose reduced the likelihood of reactions. CONCLUSION: Ultrarush
      initiation increases the risk of systemic reactions. A lower maintenance dose
      reduces the risk of repeated reactions, but the effect on treatment efficacy is
      unknown.

PMID- 22460068
TI  - Effect of epinephrine on platelet-activating factor-stimulated human vascular
      smooth muscle cells.
AB  - BACKGROUND: Animal and human data show that platelet-activating factor (PAF)
      mediates the life-threatening manifestations of anaphylaxis. Although
      administration of epinephrine is the mainstay of therapy of acute anaphylaxis,
      the interaction between epinephrine and PAF has not been studied. In particular,
      the effect of the timing of epinephrine administration on the action of PAF has
      not been examined. OBJECTIVE: Using human vascular smooth muscle cells (HVSMCs),
      we examined the effect of timing of epinephrine addition on the action of PAF.
      METHODS: The effect of epinephrine on PAF-mediated prostaglandin E(2) (PGE(2))
      release from human aortic smooth muscle cells was examined. Epinephrine was added
      at various times before and after PAF stimulation. RESULTS: HVSMCs stimulated
      with PAF released PGE(2) in a concentration- and time-dependent manner. Whereas
      preincubation of HVSMCs with epinephrine before the addition of PAF suppressed
      PGE(2) release, treatment with epinephrine after PAF stimulation was less
      effective with time after PAF stimulation. PGE(2) release was suppressed by means
      of preincubation with 8-bromo-cyclic AMP and forskolin. CONCLUSIONS: PAF induced
      PGE(2) release from HVSMCs in a concentration- and time-dependent manner, and
      early addition of epinephrine was essential for the control of PAF-induced PGE(2)
      release. Epinephrine was most effective when administered before stimulation with
      PAF but was progressively less effective with time after PAF stimulation.

PMID- 22460069
TI  - RAGE processing in chronic airway conditions: involvement of Staphylococcus
      aureus and ECP.
AB  - BACKGROUND: The receptor for advanced glycation end products (RAGE) is a
      multiligand receptor that exists as a membrane-bound (mRAGE) form and a soluble
      (sRAGE) form. RAGE is reported to play a role in diverse pathologies including
      lower airway conditions, but the exact mechanism of action remains poorly
      understood. In the upper airways, the involvement of RAGE remains completely
      unexplored. OBJECTIVE: To investigate the involvement of RAGE in the human upper
      airway conditions chronic rhinosinusitis without nasal polyps (CRSsNP) and
      chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Protein levels of
      sRAGE, mRAGE, IL-5, and eosinophil cationic protein (ECP) were quantitatively
      assessed in inflamed tissue of CRSsNP and CRSwNP patients. Nasal tissue of
      subjects without disease served as control. Ex vivo human sinonasal tissue
      stimulation assays were used to assess the effect of Staphylococcus aureus and
      ECP on sRAGE processing. RESULTS: sRAGE protein levels were higher in CRSsNP
      tissue, whereas mRAGE protein levels were lower than in controls. In CRSwNP
      patients, both tissue sRAGE and mRAGE protein levels were reduced. Low tissue
      sRAGE protein concentrations were associated with high IL-5 and ECP protein
      levels. In vitro, S aureus induced the release of sRAGE from the tissue, while
      ECP was shown to be implicated in the breakdown of free sRAGE. CONCLUSIONS: We
      demonstrate for the first time that RAGE protein is highly expressed in human
      upper airways under normal physiology and that it is subject to differential
      processing in CRSsNP and CRSwNP, identifying S aureus and ECP as novel and
      crucial players in this process.

PMID- 22460070
TI  - A critical role of IL-33 in experimental allergic rhinitis.
AB  - BACKGROUND: We reported previously that serum levels of IL-33 are significantly
      increased in patients with allergic rhinitis (AR). However, very little is known
      about the role of IL-33 for the development of AR. OBJECTIVE: We thought to
      develop a novel murine model of ragweed pollen-specific AR and examined the
      pathologic role for ragweed-induced IL-33 in the development of AR manifestation
      using IL-33-deficient (il33(-/-)) mice. METHODS: Ragweed-immunized and ragweed
      challenged mice were examined for early- and late-phase nasal responses. IL-33
      protein expression in the nasal epithelial cells of the AR murine model and
      patients with AR were assessed by using confocal microscopy. RESULTS: After nasal
      challenge with ragweed pollen, ragweed-immunized wild-type mice manifested early
      phase (sneezing) and late-phase (eosinophilic and basophilic accumulation)
      responses. In contrast, il33(-/-) and FcepsilonRI(-/-) mice did not have both
      early- and late-phase AR responses. IL-33 protein was constitutively expressed in
      the nucleus of nasal epithelial cells and was promptly released into nasal fluids
      in response to nasal exposure to ragweed pollen. In human subjects we revealed
      constitutive expression of IL-33 protein in the nasal epithelial cells of healthy
      control subjects and downregulated expression of IL-33 protein in inflamed nasal
      epithelial cells of patients with AR. IL-33-stimulated mast cells and basophils
      contributed to the early- and late-phase AR manifestation through increasing
      histamine release and production of chemoattractants for eosinophils/basophils,
      respectively. CONCLUSIONS: Ragweed pollen-driven endogenous IL-33 contributed to
      the development of AR responses. IL-33 might present an important therapeutic
      target for the prevention of AR.

PMID- 22460071
TI  - Antiviral IFN-gamma responses of monocytes at birth predict respiratory tract
      illness in the first year of life.
AB  - BACKGROUND: Viral respiratory tract infections are the leading cause of acute
      illness during infancy and are closely linked to chronic inflammatory airway
      diseases later in life. However, the determinants of susceptibility to acute
      respiratory tract infections still need to be defined. OBJECTIVE: We investigated
      whether the individual variation in antiviral response at birth determines the
      risk for acute respiratory tract illness in the first year of life. METHODS: We
      studied 82 children who were enrolled in a birth cohort study of inner-city
      children with at least 1 parent with allergy or asthma. We cultured cord blood
      monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after
      inoculation with respiratory syncytial virus. We also monitored the frequency of
      acute respiratory tract illness at 3-month intervals and analyzed nasal lavage
      samples for respiratory tract viruses at the time of illness during the first
      year. RESULTS: Respiratory tract infection was reported for 88% of subjects, and
      respiratory tract viruses were recovered in 74% of symptomatic children. We
      observed a wide range of antiviral responses in cord blood monocytes across the
      population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in
      response to respiratory syncytial virus infection of monocytes was associated
      with a significant increase in the frequency of upper respiratory tract
      infections (r = -0.42, P < .001) and the prevalence of ear and sinus infections,
      pneumonias, and respiratory-related hospitalizations. CONCLUSION: Individual
      variations in the innate immune response to respiratory tract viruses are
      detectable even at birth, and these differences predict the susceptibility to
      acute respiratory tract illness during the first year of life.

PMID- 22460073
TI  - Vitamin D binding protein and asthma severity in children.

PMID- 22460072
TI  - Naive T cells sense the cysteine protease allergen papain through protease
      activated receptor 2 and propel TH2 immunity.
AB  - BACKGROUND: Sensitization to protease allergens, such as papain, or helminth
      infection is associated with basophil recruitment to draining lymph nodes (LNs).
      Basophils have the capacity to present antigen to naive T cells and promote T(H)2
      differentiation directly or indirectly through IL-4 production. OBJECTIVE: We
      studied how papain induces basophil migration to LNs and the contribution of
      various leukocytes to papain-induced immune responses. METHODS: We immunized mice
      in the footpad with papain and studied leukocyte recruitment and inflammatory
      cytokine and chemokine production in the draining popliteal LNs. RESULTS: Papain
      directly activated naive T cells through protease-activated receptor (PAR) 2 to
      initiate a chemokine/cytokine program that includes CCL17, CCL22, and IL-4.
      Papain-triggered innate immune responses were dependent on both CD4 T cells and
      PAR2 and were strongly reduced in the absence of CCR4, the primary receptor for
      CCL17/CCL22. CONCLUSION: These results elucidate a novel innate allergen
      recognition pathway mediated by naive T cells through PAR2, which provide an
      immediate source of chemokines and IL-4 upstream of basophils and antigen
      restricted T(H)2 differentiation. PAR2 antagonism might thus hold promise for the
      treatment of allergic disease.

PMID- 22460074
TI  - Contemporary consensus proposal on criteria and classification of eosinophilic
      disorders and related syndromes.
AB  - Eosinophilia is an important indicator of various neoplastic and nonneoplastic
      conditions. Depending on the underlying disease and mechanisms, eosinophil
      infiltration can lead to organ dysfunction, clinical symptoms, or both. During
      the past 2 decades, several different classifications of eosinophilic disorders
      and related syndromes have been proposed in various fields of medicine. Although
      criteria and definitions are, in part, overlapping, no global consensus has been
      presented to date. The Year 2011 Working Conference on Eosinophil Disorders and
      Syndromes was organized to update and refine the criteria and definitions for
      eosinophilic disorders and to merge prior classifications in a contemporary
      multidisciplinary schema. A panel of experts from the fields of immunology,
      allergy, hematology, and pathology contributed to this project. The expert group
      agreed on unifying terminologies and criteria and a classification that
      delineates various forms of hypereosinophilia, including primary and secondary
      variants based on specific hematologic and immunologic conditions, and various
      forms of the hypereosinophilic syndrome. For patients in whom no underlying
      disease or hypereosinophilic syndrome is found, the term hypereosinophilia of
      undetermined significance is introduced. The proposed novel criteria,
      definitions, and terminologies should assist in daily practice, as well as in the
      preparation and conduct of clinical trials.

PMID- 22460076
TI  - Glycidyl fatty acid esters in food by LC-MS/MS: method development.
AB  - An improved method based on liquid chromatography-tandem mass spectrometry (LC
      MS/MS) for the analysis of glycidyl fatty acid esters in oils was developed. The
      method incorporates stable isotope dilution analysis (SIDA) for quantifying the
      five target analytes: glycidyl esters of palmitic (C16:0), stearic (C18:0), oleic
      (C18:1), linoleic (C18:2) and linolenic acid (C18:3). For the analysis, 10 mg
      sample of edible oil or fat is dissolved in acetone, spiked with deuterium
      labelled analogs of glycidyl esters and purified by a two-step chromatography on
      C18 and normal silica solid phase extraction (SPE) cartridges using methanol and
      5% ethyl acetate in hexane, respectively. If the concentration of analytes is
      expected to be below 0.5 mg/kg, 0.5 g sample of oil is pre-concentrated first
      using a silica column. The dried final extract is re-dissolved in 250 MUL of a
      mixture of methanol/isopropanol (1:1, v/v), 15 MUL is injected on the analytical
      C18 LC column and analytes are eluted with 100% methanol. Detection of target
      glycidyl fatty acid esters is accomplished by LC-MS/MS using positive ion
      atmospheric pressure chemical ionization operating in Multiple Reaction
      Monitoring mode monitoring 2 ion transitions for each analyte. The method was
      tested on replicates of a virgin olive oil which was free of glycidyl esters. The
      method detection limit was calculated to be in the range of 70-150 MUg/kg for
      each analyte using 10 mg sample and 1-3 MUg/kg using 0.5 g sample of oil. Average
      recoveries of 5 glycidyl esters spiked at 10, 1 and 0.1 mg/kg were in the range
      84% to 108%. The major advantage of our method is use of SIDA for all analytes
      using commercially available internal standards and detection limits that are
      lower by a factor of 5-10 from published methods when 0.5 g sample of oil is
      used. Additionally, MS/MS mass chromatograms offer greater specificity than
      liquid chromatography-mass spectrometry operated in selected ion monitoring mode.
      The method will be applied to the survey of glycidyl fatty acid esters in food
      products on the Canadian market.

PMID- 22460077
TI  - Posttranslational modification of indoleamine 2,3-dioxygenase.
AB  - Protein posttranslational modifications (PTMs) perform essential roles in the
      biological regulation of a cell. PTMs are extremely important because they can
      change a protein's physical or chemical properties, conformation, activity,
      cellular location, or stability. In fact, most proteins are altered by the
      addition or removal of a chemical moiety on either an amino acid or the protein's
      N- or C-terminus. Some PTMs can be added and removed dynamically as a mechanism
      for reversibly controlling protein function. Thus, identifying the PTM sites is
      critical to fully understand the biological roles of any given protein. Mass
      spectrometry (MS) is a widely used analytical strategy to identify PTMs. We have
      used an automated two-dimensional liquid chromatography (LC) system coupled with
      electrospray ionization quadrupole ion-trap MS to identify PTMs for indoleamine
      2,3-dioxygenase 1 (IDO1), one of the tryptophan catabolic enzymes. IDO1 promotes
      immune tolerance by suppressing local T-cell responses under various
      physiological and pathophysiological conditions, such as pregnancy in mammals,
      tumor resistance, autoimmunity, and chronic inflammation. Although many studies
      have demonstrated the biological importance of IDO activity, the PTMs of IDO
      enzymes remain largely unknown. Only a few important PTMs of IDO1 have been
      found, such as nitration, N-terminal acetylation, and phosphorylation. In this
      review, we analyze the PTMs of IDO1 using our two-dimensional LC-MS/MS system,
      and provide an overview of our current understanding.

PMID- 22460075
TI  - Multiscale systems biology and physics of thrombosis under flow.
AB  - Blood clotting under hemodynamic conditions involves numerous multiscale
      interactions from the molecular scale to macroscopic vessel and systemic
      circulation scales. Transmission of shear forces to platelet receptors such as
      GPIbalpha, P-selectin, alpha(2)beta(1), and alpha(2b)beta(3) controls adhesion
      dynamics. These forces also drive membrane tether formation, cellular
      deformation, and mechanosignaling in blood cells. Blood flow results in red blood
      cell (RBC) drift towards the center of the vessel along with a near-wall plasma
      layer enriched with platelets. RBC motions also dramatically enhance platelet
      dispersion. Trajectories of individual platelets near a thrombotic deposit
      dictate capture-activation-arrest dynamics as these newly arriving platelets are
      exposed to chemical gradients of ADP, thromboxane, and thrombin within a micron
      scale boundary layer formed around the deposit. If shear forces are sufficiently
      elevated (>50 dyne/cm(2)), the largest polymers of von Willebrand Factor may
      elongate with concomitant shear-induced platelet activation. Finally, thrombin
      generation enhances platelet recruitment and clot strength via fibrin
      polymerization. By combination of coarse-graining, continuum, and stochastic
      algorithms, the numerical simulation of the growth rate, composition, and
      occlusive/embolic potential of a thrombus now spans multiscale phenomena. These
      simulations accommodate particular flow geometries, blood phenotype,
      pharmacological regimen, and reactive surfaces to help predict disease risk or
      response to therapy.

PMID- 22460078
TI  - Comparison of data analysis parameters and MS/MS fragmentation techniques for
      quantitative proteome analysis using isobaric peptide termini labeling (IPTL).
AB  - Isobaric peptide termini labeling (IPTL) is a quantification method which permits
      relative quantification using quantification points distributed throughout the
      whole tandem mass spectrometry (MS/MS) spectrum. It is based on the complementary
      derivatization of peptide termini with different isotopes resulting in isobaric
      peptides. Here, we use our recently developed software package IsobariQ to
      investigate how processing and data analysis parameters can improve IPTL data.
      Deisotoping provided cleaner MS/MS spectra and improved protein identification
      and quantification. Denoising should be used with caution because it may remove
      highly regulated ion pairs. An outlier detection algorithm on the ratios within
      every individual MS/MS spectrum was beneficial in removing false-positive
      quantification points. MS/MS spectra using IPTL typically contain two peptide
      series with complementary labels resulting in lower Mascot ion scores than non
      labeled equivalent peptides. To avoid this penalty, the two chemical
      modifications for IPTL were specified as variables including satellite neutral
      losses of tetradeuterium with positive loss for the heavy isotopes and negative
      loss for the light isotopes. Thus, the less dominant complementary ion series
      were not considered for the scoring, which improved the ion scores significantly.
      In addition, we showed that IPTL was suitable for fragmentation by electron
      transfer dissociation (ETD) and higher energy collisionally activated
      dissociation (HCD) besides the already reported collision-induced dissociation
      (CID). Notably, ETD and HCD data can be identified and quantified using IsobariQ.
      ETD outperformed CID and HCD only for charge states >=4+ but yielded in total
      fewer protein identifications and quantifications. In contrast, the high
      resolution information of HCD fragmented peptides provided most identification
      and quantification results using the same scan speed.

PMID- 22460079
TI  - Development of a simultaneous analytical method for selected anorectics,
      methamphetamine, MDMA, and their metabolites in hair using LC-MS/MS to prove
      anorectics abuse.
AB  - Owing to the tight control of methamphetamine, it is presumed that phentermine,
      an amphetamine-type anorectic, has recently been considered a supplement for
      methamphetamine abusers in Korea. In addition, the abuse of other anorectics
      obtained by inappropriate means has become a social issue. Hair is a useful
      specimen to prove chronic drug use. Therefore, an analytical method for the
      simultaneous detection of phentermine, phendimetrazine, amfepramone,
      fenfluramine, mazindol, methamphetamine, and 3,4-methylenedioxymethamphetamine
      (MDMA), as well as their metabolites, which covers the major amphetamines and
      anorectic agents in Korea, in hair was established and validated using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The drugs and their
      metabolites in hair were extracted using 1 % HCl in methanol and then filtered
      and analyzed by LC-MS/MS with electrospray ionization in positive mode. The
      validation results for selectivity, linearity, matrix effect, recovery, process
      efficiency, intra- and interassay precision and accuracy, and processed sample
      stability were satisfactory. The limits of detection ranged from 0.025 to 1 ng/10
      mg hair and the limits of quantification were 0.25 ng/10 mg hair for every
      analyte except mazindol and phentermine, for which they were 10 ng/10 mg hair.
      The method was successfully applied for the segmental determination of selected
      anorectics, methamphetamine, MDMA, and their metabolites in hair from 39 drug
      suspects. Among the anorectics, phentermine and/or phendimetrazine were
      identified with or without methamphetamine in the hair samples. Closer
      supervision of the inappropriate use of anorectics is necessary. Also, hair
      analysis is useful for monitoring the abuse potential of unnoticed drugs.

PMID- 22460080
TI  - Delivery of a chromosomally normal child from an oocyte with reciprocal aneuploid
      polar bodies.
AB  - PURPOSE: To demonstrate that a euploid embryo derived from an oocyte with
      reciprocal aneuploid polar bodies is capable of producing a chromosomally normal
      child. METHODS: A case report of maternal MI error compensation where single
      nucleotide polymorphism (SNP) microarray based comprehensive chromosome screening
      (CCS) was performed on the 1st and 2nd polar body, the resulting embryo, and
      newborn DNA. RESULTS: CCS performed after embryo transfer identified a
      chromosomally normal embryo that resulted from an oocyte with reciprocal
      aneuploid polar bodies. The first polar body was found to be missing a single
      chromatid derived from chromosome 21 and the second polar body possessed an extra
      chromatid derived from chromosome 21. Compensation of the maternal meiotic error
      was verified by CCS analysis of a trophectoderm biopsy from the resulting
      blastocyst which was euploid for all 23 pairs of chromosomes. DNA fingerprinting
      and CCS of the resulting newborn confirmed a chromosomally normal child,
      demonstrating the developmental potential of an oocyte with reciprocal aneuploid
      polar bodies. CONCLUSIONS: This is the first case report demonstrating the
      reproductive potential of a chromosomally normal embryo derived from an oocyte
      which had undergone meiosis I error. Systematic investigation into the frequency
      of meiosis I error compensation and the negative predictive value of polar body
      aneuploidy screening for reproductive potential should be conducted in order to
      confirm clinical relevance.

PMID- 22460081
TI  - A successful subsequent pregnancy after fetal reduction of one of the monozygotic
      twins: a case report.

PMID- 22460082
TI  - A randomized clinical trial comparing embryo culture in a conventional incubator
      with a time-lapse incubator.
AB  - PURPOSE: Time-lapse monitoring allows for a flexible embryo evaluation and
      potentially provides new dynamic markers of embryo competence. Before introducing
      time-lapse monitoring in a clinical setting, the safety of the instrument must be
      properly documented. Accordingly, the aim of this study was to evaluate the
      safety of a commercially available time-lapse incubator. METHODS: In a two
      center, randomized, controlled, clinical trial 676 oocytes from 59 patients in
      their 2nd or third treatment cycle, age <38 years and >= 8 oocytes retrieved were
      cultured in the time-lapse incubator or in a conventional incubator. The primary
      outcome was proportion of 4-cell embryos on day 2. Secondary outcomes were
      proportion of 7-8 cell embryos on day 3 and proportion of blastocysts on day 5.
      Implantation pregnancy rates were registered based on presence of fetal heart
      activity visualized by ultrasound 8 weeks after embryo transfer. RESULTS: No
      significant difference was found between the time-lapse incubator (TLI) and
      conventional incubator (COI) in proportion of 4-cell embryos on day 2
      irrespective of whether data was analyzed according to ITT (RR(TLI/COI): 0.81
      (0.65; 1.02)) or PP (RR(TLI/COI): 0.80 (0.63; 1.01)). Nor were any significant
      differences detected in the secondary endpoints; i.e. proportion of 7-8-cell
      embryos on day three ITT (RR(TLI/COI): 0.96 (0.73; 1.26)); PP (RR(TLI/COI): 0.95
      (0.72; 1.26)) and proportion of blastocysts on day five ITT (RR(TLI/COI): 1.09
      (0.84; 1.41)); PP (RR(TLI/COI): 1.09 (0.83: 1.41)). We found no differences in
      clinical pregnancy rate or implantation rate. CONCLUSION: Culture in the time
      lapse incubator supports embryonic development equally to a conventional
      incubator.

PMID- 22460083
TI  - A preliminary 6-month prospective study examining self-reported religious
      preference, religiosity/spirituality, and retention at a Jewish residential
      treatment center for substance-related disorders.
AB  - Although there is a substantial amount of research suggesting that higher levels
      of religiosity/spirituality (R/S) are associated with better treatment outcomes
      of substance-related disorders, no studies have explored this relationship at a
      faith-based residential treatment center. The objective of this prospective study
      is to explore the relationship between R/S, self-reported religious preference,
      and retention at a Jewish residential treatment center for substance-related
      disorders. Using the Daily Spiritual Experience Scale, R/S levels were assessed
      for 33 subjects at baseline, 1 month, 3 months, and 6 months. Results
      demonstrated a significant relationship between baseline R/S level and retention
      at 6 months, while R/S levels were unchanged during the course of treatment.
      Notably, no relationship was found between self-reported religious affiliation
      and retention. This study demonstrates that patients' R/S level, rather than
      religious affiliation, is a possible predictor for better outcome at faith-based
      residential centers for substance-related disorders.

PMID- 22460084
TI  - Brain derived neurotrophic factor inhibits apoptosis in enteric glia during gut
      inflammation.
AB  - BACKGROUND: Enteric glia cells (EGCs) are essential for the integrity of the
      bowel. A loss of EGCs leads to a severe inflammation of the intestines. As a
      diminished EGC network is postulated in Crohn's disease (CD), we aimed to
      investigate if EGCs could be a target of apoptosis during inflammation in CD,
      which can be influenced by Brain derived neurotrophic factor (BDNF).
      MATERIAL/METHODS: GFAP, BDNF and cCaspase-3 were detected in the gut of patients
      with CD. Primary EGC cultures were established and cultivated. Tyrosine receptor
      kinase (TrkB) receptors on these cells were investigated by western blot and
      immunofluorescence. Rate of apoptosis was induced by tumor necrosis factor (TNF
      alpha) and interferon (IFN-gamma). Apoptosis was determined by a fluorometric
      caspase 3/7 activation assay after preincubation of these cells with BDNF or
      neutralizing anti-BDNF antibodies. RESULTS: Mucosal GFAP-positive EGCs undergo
      apoptosis revealed by cCaspase-3 in the gut of patients with CD expressing BDNF
      highly. The combination of TNF-alpha and IFN-gamma was able to induce apoptosis
      in primary EGCs, whereas these factors alone did not. Brain derived neurotrophic
      factor (BDNF) attenuate glia cell apoptosis to a small extent, but neutralizing
      antibodies against BDNF dramatically increased apoptosis. CONCLUSIONS: Mucosal
      EGC apoptosis is an important finding in the gut of patients with CD.
      Proinflammatory cytokines, which are highly increased in CD, induce EGC
      apoptosis, whereas the neurotrophin BDNF might be protective for EGC. Since EGCs
      are implicated in the maintenance of the enteric mucosal integrity, EGC apoptosis
      may contribute to the pathophysiological changes in CD.

PMID- 22460085
TI  - Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) expression in
      human benign and malignant thyroid lesions.
AB  - BACKGROUND: The receptor-binding cancer antigen expressed on SiSo cells (RCAS1)
      is a human tumor-associated antigen that contributes to tumor progression by
      enabling cancer cells to evade immune surveillance. The present study aimed to
      evaluate the clinical significance of RCAS1 expression in human benign and
      malignant thyroid lesions. MATERIAL/METHODS: RCAS1 protein expression was
      assessed immunohistochemically on paraffin-embedded thyroid tissues from 121
      patients with benign and malignant lesions and was associated with type of
      thyroid histopathology and tumor stage parameters such as tumor size, lymph node
      metastases, capsular, lymphatic and vascular invasion. RESULTS: RCAS1 positivity,
      overexpression and staining intensity provided a distinct discrimination between
      benign and malignant thyroid cases (p=0.0006, p=0.0001 and p=0.0001,
      respectively), as well as between hyperplastic nodule and papillary carcinoma
      cases (p=0.0229, p=0.0001 and p=0.0001, respectively). RCAS1 positivity,
      overexpression and staining intensity also provided distinct discrimination
      between cases with Hashimoto thyroiditis and those with hyperplastic nodule
      (p=0.0221, p=0.0001 and p=0.0019, respectively). In the subgroup of malignant
      thyroid lesions, RCAS1 overexpression was significantly associated with large
      tumor size (p=0.0246), the presence of lymph node metastases (p=0.0351) and
      capsular invasion (p=0.0397). CONCLUSIONS: RCAS1 protein may participate in
      thyroid neoplastic transformation and could be considered as a useful biomarker
      to improve diagnostic scrutiny.

PMID- 22460086
TI  - VEGF and metalloproteinase 2 (MMP 2) expression in gastric cancer tissue.
AB  - BACKGROUND: Neoplasms are the second leading cause of death in Poland after
      vessel diseases, despite the huge progress in medical sciences in the last 20
      years. Recently, gastric cancer morbidity has decreased, but mortality is still
      at a high level. MATERIAL/METHODS: Tissues from 24 patients with a
      histopathologically diagnosed mucosal and adenomucosal gastric cancer were
      tested. Patients were divided into 2 equal groups: patients without metastases
      (G1) and patients with metastases in the liver (G2). In all tested tissues of G1
      and G2, the expression of VEGF (vascular endothelial growth factor) and
      metalloproteinase 2, respectively, were estimated. RESULTS: Results revealed a
      statistically significant increase in the VEGF expression for G1 and G2 in
      relation to the margin (p1<0.001; p2<0.001). The increase of gene expression for
      VEGF did not significantly differ statistically in G1 and G2. The obtained
      results revealed a statistically significant difference in the increase of gene
      expression for MMP-2 in G1 in relation to the margin (p<0.05) and a very high one
      in G2 in relation to the average margin value (p<0.001). A highly statistically
      significant correlation was obtained for VEGF and MMP-2 in the tissue of patients
      with metastases (p<0.001; r=0.714). The highly elevated expression of MMP-2 in
      the tissue of gastric cancer in patients with metastases confirms its
      participation in the invasiveness of the neoplasmatic process. CONCLUSIONS: The
      highly significant correlation between VEGF and MMP-2 suggests a connection
      between both mechanisms in the progression of gastric cancer.

PMID- 22460087
TI  - Is pimecrolimus cream (1%) an appropriate therapeutic agent for the treatment of
      external ear atopic dermatitis?
AB  - BACKGROUND: In recent years, pimecrolimus 1% cream has been demonstrated to
      reduce symptoms of atopic dermatitis in patients when applied topically.
      MATERIAL/METHODS: In our study we compared the therapeutic effects of local 1%
      pimecrolimus to 1% hydrocortisone, and to a control group in a mouse model with
      atopic dermatitis in the external ear canals. Atopic dermatitis was created by
      application of Dinitrochlorobenzene in the external ear canals of mice. The
      development of atopic dermatitis was detected by clinical observation score and
      determination of total serum IgE levels. Pimecrolimus and hydrocortisone cream
      were topically applied to the external ear canal skin once a day for 14 days.
      RESULTS: There was no significant difference between the hydrocortisone and the
      pimecrolimus therapy groups, while there was a statistically significant
      difference between these 2 groups and the control group (p<0.05) Assessment of
      the clinical observation scoring carried out on the 14th day of therapy revealed
      that there was no difference between the hydrocortisone and pimecrolimus groups.
      Biopsies were taken on the 14th day following treatment. Tissue samples were
      histologically evaluated; contact dermatitis was observed microscopically in the
      control group, but in the therapy groups only minimal evidence of contact
      dermatitis was found. CONCLUSIONS: The results of our study reveal that the
      therapeutic efficacy of 1% pimecrolimus was equivalent to 1% hydrocortisone
      treatment in the artificially developed atopic dermatitis model in external ear
      canals of mice. These results clearly demonstrate that 1% pimecrolimus cream can
      be an effective alternative therapeutic agent in cases where steroid treatment
      proves to be insufficient or in cases where treatment must be discontinued due to
      its adverse effects.

PMID- 22460088
TI  - Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis.
AB  - BACKGROUND: Radiation often causes depletion of immunocytes in tissues and blood,
      which results in immunosuppression. Molecular hydrogen (H2) has been shown in
      recent studies to have potential as a safe and effective radioprotective agent
      through scavenging free radicals. This study was designed to test the hypothesis
      that H2 could protect immunocytes from ionizing radiation (IR). MATERIAL/METHODS:
      H2 was dissolved in physiological saline or medium using an apparatus produced by
      our department. A 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF)
      probe was used to detect intracellular hydroxyl radicals (*OH). Cell apoptosis
      was evaluated by annexin V-FITC and Propidium iodide (PI) staining as well as the
      caspase 3 activity. Finally, we examined the hematological changes using an
      automatic Sysmex XE 2100 hematology analyzer. RESULTS: We demonstrated H2-rich
      medium pretreatment reduced *OH level in AHH-1 cells. We also showed H2 reduced
      radiation-induced apoptosis in thymocytes and splenocytes in living mice.
      Radiation-induced caspase 3 activation was also attenuated by H2 treatment.
      Finally, we found that H2 rescued the radiation-caused depletion of white blood
      cells (WBC) and platelets (PLT). CONCLUSIONS: This study suggests that H2
      protected the immune system and alleviated the hematological injury induced by
      IR.

PMID- 22460089
TI  - MicroRNA-125b down-regulation mediates endometrial cancer invasion by targeting
      ERBB2.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding nucleotides that regulate
      mRNA stability and protein expression by imperfect base pairing with the 3'
      untranslated region (3'UTR) of target mRNAs. Many miRNAs have been documented to
      be aberrantly expressed in human cancers, but the role of miRNAs in endometrioid
      endometrial cancer (EEC) remains poorly understood. The objective of this study
      was to investigate the effect of miR-125b on EEC development and to explore its
      molecular mechanism in EEC carcinogenesis. MATERIAL/METHODS: Real-time
      quantitative PCR was applied to evaluate the expression level of miRNA-125b in
      EEC and normal endometrium (NE) samples. The invasion ability of miR-125b in EEC
      HEC1B cells was analyzed by Transwell assay after pre-miR-125b or anti-miR-125b
      transfection. For the invasion mechanism analysis of miR-125b on HEC1B cells,
      miRBase, TargetScan, miRanda and PicTar were used to predict the possible target
      gene of miR-125b. Luciferase activities assay, cotransfection and Western blot
      were used to reveal that the predicted target genes of miR-125b were direct and
      specific. RNA interference technology was used to confirm that the invasion
      inhibition of miR-125b was directly induced by ERBB2. RESULTS: Our study showed
      that miR-125b was down-regulated in human EEC specimens compared to that in NC
      specimens. Over-expression of miR-125b in HEC1B cells inhibited EEC invasion and
      this inhibitory effect on HEC1B cells could be restored by miR-125b knock down.
      Mechanism analysis revealed that ERBB2 was a direct and specific target of miR
      125b. The inhibitory effect on EEC cell invasion was mediated by miR-125b
      inhibition of the translation of a proto-oncogene, ERBB2. CONCLUSIONS: Aberrantly
      expressed miR-125b contributes to HEC1B cells invasion partly through directly
      down-regulating ERBB2 protein expression in EEC. This miRNA signature offers a
      novel potential therapeutic strategy for EEC.

PMID- 22460090
TI  - Increased expression of DNA repair gene XPF enhances resistance to
      hydroxycamptothecin in bladder cancer.
AB  - BACKGROUND: Xeroderma pigmentosum group F (XPF) is an important participant in
      the nucleotide excision repair process. This study aimed to investigate the
      expression of DNA repair gene xeroderma pigmentosum group F (XPF) in bladder
      cancer and its clinical significance. MATERIAL/METHODS: Total RNA and protein
      were extracted from 45 untreated bladder cancer tissues and 21
      hydroxycamptothecin (HCPT)-treated bladder cancer specimens. Real-time PCR and
      Western blot assay were used to detect the mRNA and protein levels of XPF,
      respectively. siRNA targeting XPF was used to knock down the XPF expression in
      T24 cells and 5637 cells, and the sensitivity of XPF-depleted cells to HCPT was
      measured. RESULTS: The XPF expressions in the HCPT-treated cancer tissues was
      significantly higher than those in the untreated cancer tissues at both mRNA and
      protein levels. Importantly, the enhanced XPF expression decreased the
      sensitivity of T24 cells and 5637 cells to HCPT. Furthermore, the HCPT treatment
      significantly increased the apoptosis of T24 cells and 5637 cells. Alternatively,
      after the XPF gene silencing, the chemotherapeutic resistance of bladder cancer
      cells was significantly decreased. CONCLUSIONS: Our results show the increased
      expression of XPF is involved in the chemotherapeutic resistance of bladder
      cancer, and decreasing XPF expression may become a promising therapeutic strategy
      for bladder cancer.

PMID- 22460091
TI  - The interrelationship between air temperature and humidity as applied locally to
      the skin: the resultant response on skin temperature and blood flow with age
      differences.
AB  - BACKGROUND: Most studies of the skin and how it responds to local heat have been
      conducted with either water, thermodes, or dry heat packs. Very little has been
      accomplished to look at the interaction between air humidity and temperature on
      skin temperature and blood flow. With variable air temperatures and humidity's
      around the world, this, in many ways, is a more realistic assessment of
      environmental impact than previous water bath studies. MATERIAL/METHODS: Eight
      young and 8 older subjects were examined in an extensive series of experiments
      where on different days, air temperature was 38, 40, or 42 degrees C. and at each
      temperature, humidity was either 0%, 25%, 50%, 75%, or 100% humidity. Over a 20
      minute period of exposure, the response of the skin in terms of its temperature
      and blood flow was assessed. RESULTS: For both younger and older subjects, for
      air temperatures of 38 and 40 degrees C., the humidity of the air had no effect
      on the blood flow response of the skin, while skin temperature at the highest
      humidity was elevated slightly. However, for air temperatures of 42 degrees C.,
      at 100% humidity, there was a significant elevation in skin blood flow and skin
      temperature above the other four air humidity's (p<0.05). In older subjects, the
      blood flow response was less and the skin temperature was much higher than
      younger individuals for air at 42 degrees C. and 100% humidity (p<0.05).
      CONCLUSIONS: Thus, in older subjects, warm humid air caused a greater rise in
      skin temperature with less protective effect of blood flow to protect the skin
      from overheating than is found in younger subjects.

PMID- 22460092
TI  - Long-term echocardiographic changes in left ventricular size and function
      following surgery for severe mitral regurgitation.
AB  - BACKGROUND: Chronic mitral regurgitation (MR) results in a state of chronic left
      ventricular (LV) volume overload, resulting in compensatory dilatation. Mitral
      valve (MV) surgery for regurgitation reduces LV preload but increases LV
      afterload. Few data are available documenting subsequent changes in LV size and
      function over time following MV surgery for severe regurgitation in unselected
      populations. MATERIAL/METHODS: Pre- and postoperative echocardiograms (n=454)
      acquired from 108 consecutive patients with chronic MR who underwent MV surgery
      were analyzed. RESULTS: LV diastolic diameter was 4 mm smaller on postoperative
      compared to preoperative exams, whereas LV fractional shortening (FS) was
      unchanged. Linear regression analysis showed no change in LV diastolic diameter
      over time postoperatively, whereas LV FS increased over time following surgery.
      Improvement in LV FS occurred at an average rate of 1.6% per year (95% CI, 0.2
      2.9). Subgroups were small, but the same secular trends were generally noted in
      groups with or without coronary artery bypass graft surgery (CABGS) and in those
      with or without mitral leaflet disease. CONCLUSIONS: Following MV surgery for MR,
      LV diastolic diameter reduces by 2 mm at the time of surgery, but then remains
      stable over time. Improvement in LV function over time postoperatively was only
      seen in those without concomitant CABGS, possibly related to less baseline
      myocardial scarring in this group.

PMID- 22460093
TI  - Intravenous vitamin C in the treatment of shingles: results of a multicenter
      prospective cohort study.
AB  - BACKGROUND: Vitamin C is an immune-relevant micronutrient, which is depleted in
      viral infections and this deficiency seems to play a critical role in the
      pathogenesis of herpes infections and in the development of postherpetic
      neuralgia. The objective of this observational multicenter study was to evaluate
      the utilization, safety and efficacy of intravenously administrated vitamin C in
      patients with shingles. MATERIAL/METHODS: Between April 2009 and December 2010 16
      general practitioners recorded data of 67 participants with symptomatic herpes
      zoster who received vitamin C intravenously (Pascorbin(r) 7.5 g/50 ml) for
      approximately 2 weeks in addition to standard treatment. The assessment of pain
      (VAS) and the dermatologic symptoms of shingles such as hemorrhagic lesions and
      the number of efflorescences were investigated in a follow-up observation phase
      of up to 12 weeks. RESULTS: Mean declines of pain scores (VAS), number of
      affected dermatomes and efflorescences, and the presence of hemorrhagic vesicles
      between the baseline and follow-up assessments at 2 and 12 weeks were
      statistically significant. Overall, 6.4% of the participants experienced post
      herpetic neuralgia. Common complaints such as general fatigue and impaired
      concentration also improved during the study. The effects and the tolerability of
      the treatment were evaluated positively by the physicians. The risk of developing
      PHN was reduced. CONCLUSIONS: The data presented here provide evidence that
      concomitant use of intravenously administered ascorbic acid may have beneficial
      effects on herpes zoster-associated pain, dermatologic findings and accompanying
      common complaints. To confirm our findings, randomized, placebo-controlled
      clinical studies are necessary.

PMID- 22460094
TI  - Effects of cigarette smoking, metabolic syndrome and dehydroepiandrosterone
      deficiency on intima-media thickness and endothelial function in hypertensive
      postmenopausal women.
AB  - BACKGROUND: Cigarette smoking is a major risk factor of atherosclerosis. The aim
      of this study was to assess the relationship between smoking and arterial
      hypertension as well as endothelial dysfunction in postmenopausal women without
      clinically manifested symptoms of atherosclerosis. MATERIAL/METHODS: The study
      groups consisted of 35 current smokers and 45 nonsmokers. The thickness of intima
      media complex (IMT), a marker of atherosclerosis, was measured in carotid
      arteries. Plasma concentrations of fasting glucose, insulin, lipoproteins,
      inflammatory markers (tumor necrosis factor-alpha, intercellular adhesion
      molecule-1), matrix metalloproteinases (metalloproteinase-9, tissue inhibitor of
      metalloproteinase-1), insulin, and dehydroepiandrosterone sulfate (DHEA-S) were
      measured. RESULTS: Smokers compared with nonsmokers showed lower fasting glucose
      levels in blood (87.0+/-10.9 and 93.2+/-13.6 mg/dl, p<0.05), higher mean systolic
      (131.1+/-15.9 vs. 123.0+/-10.9 mm Hg, p<0.05) and diastolic (81.7+/-11.4 vs.
      75.2+/-9.2 mm Hg, p<0.05) blood pressure during daytime, and higher average heart
      rate during the daytime (78.2+/-9.3/min vs. 71.5+/-9.5/min, p<0.01) and at night
      (67.2+/-10.6/min vs. 61.7+/-7.7/min, p<0.05), respectively. The IMT in the right
      carotid artery was significantly higher in smokers than in nonsmokers (0.96+/
      0.16 mm vs. 0.82+/-0.21, p<0.05) and was positively correlated with smoking
      intensity (R=0.36) and habit duration (R=0.35). The comparison of inflammatory
      markers, metalloproteinases, and DHEA-S concentrations in plasma did not reveal
      significant differences between the 2 groups. A significant negative correlation
      between DHEA-S concentration in plasma and IMT in right carotid artery was found
      in smokers. CONCLUSIONS: Smoking in hypertensive postmenopausal women is
      associated with lower fasting blood glucose and BMI values, but higher arterial
      pressure and heart rate, and increases in IMT in right carotid artery.

PMID- 22460095
TI  - The interstitial expression of alpha-smooth muscle actin in glomerulonephritis is
      associated with renal function.
AB  - BACKGROUND: In a healthy kidney, contractile protein alpha-smooth muscle actin
      (ASMA) is immunohistochemically strongly expressed only in the blood vessels,
      while in pathological conditions it can be visualized in glomerular mesangial
      cells and interstitial myofibroblasts. The aim of this study was to explore the
      possible correlation between expression of ASMA in glomerulonephritis (GN) and
      indicators of renal function. MATERIAL/METHODS: We analyzed expression of ASMA in
      percutaneous renal biopsy of 142 adult and pediatric patients with GN and its
      correlation with blood pressure, serum creatinine, creatinine clearance and 24
      hour urine protein at the time of biopsy. Immunoexpression of ASMA was analyzed
      quantitatively using computer-assisted morphometric analysis. Relative surface of
      ASMA expression in all glomeruli and interstitium was calculated for each
      patient. RESULTS: In adults and children, greater expression of ASMA in
      interstitium was associated with higher serum creatinine and reduced creatinine
      clearance. Conversely, greater ASMA expression in glomeruli was associated with
      normal or decreased serum creatinine in adults and increased creatinine clearance
      in children. In children, correlation was found between high blood pressure and
      ASMA expression in interstitium. CONCLUSIONS: We confirmed that interstitial
      expression of ASMA is associated with reduced renal function at time of biopsy.
      The connection of ASMA expression in glomeruli with lower serum creatinine and
      normal or increased creatinine clearance suggests a favorable role of this
      phenotypic change in glomerular filtration rate; further investigation is needed.

PMID- 22460096
TI  - Triple therapy: Phaco-vitrectomy with ILM peeling, retinal endophotocoagulation,
      and intraoperative use of bevacizumab for diffuse diabetic macular edema.
AB  - BACKGROUND: The aim of this study was to evaluate the visual acuity and
      structural outcomes of combined phacovitrectomy with ILM peeling, retinal
      endophotocoagulation and use of bevacizumab in patients with diffuse diabetic
      macular edema (DDME). MATERIAL/METHODS: In this prospective, nonrandomized,
      interventional study we included 29 eyes of 26 patients with DDME. The best
      corrected visual acuity (BCVA) and central retinal thickness and volume (CRT and
      CRV) were recorded at 4, 8, 12, and 16 months after surgery. RESULTS: The mean
      preoperative BCVA was 0.74+/-0.36 logMAR (0.3-1.5) and improved finally to 0.4+/
      0.24 logMAR (-0.1-1.0) p=0.000006. The mean preoperative CRT in the 1mm zone was
      516+/-184 microm (256-950) and decreased postoperatively at the last control to
      237+/-75 microm (117-489) p=0.000003. The mean preoperative CRV in the 1mm zone
      was 0.39+/-0.14 microL (0.19-0.74) and decreased postoperatively at the last
      control to 0.17+/-0.06 microL (0.09-0.36) p=0.000003. The mean preoperative CRT
      in the 6 mm zone was 407+/-105 microm (279-640) and decreased postoperatively at
      the last control to 282+/-40 um (212-380) p=0.000004. The mean preoperative CRV
      in the 6 mm zone was 11.4+/-2.9 microL (7.85-17.93) and decreased postoperatively
      at the last control to 7.92+/-1.0 microL (5.62-10.97) p=0.000003. The 23 (79.3%)
      eyes showed improvement in BCVA >=0.2 logMAR, 5 (17.2%) eyes improvement or
      stabilization of BCVA and 1(3.5%) eye deterioration. Preoperative BCVA was a
      positive factor for prognosis of BCVA at 12th month follow-up (b=0.42; p=0.006),
      while the negative factors were: previous panretinal photocoagulation (b=-0.24;
      p=0.04), presence of vitreomacular traction (b=-0.29; p=0.02) and preoperative
      CRT in the 1000 microm zone (b=-0.24; p=0.07). A greater visual acuity
      improvement occurred in eyes with worse baseline visual acuity (b=-1.01;
      p=0.00001). The presentation of vitreomacular traction (b=-0.38; p=0.02),
      previous panretinal photocoagulation (b=-0.31, p=0.04) and greater preoperative
      CRT in the 1000 um zone (b=-0.31; p=0.07) were negative factors for visual
      improvement. CONCLUSIONS: This combined treatment resulted in improvement or
      stabilization of BCVA and decrease of CRT and CRV. Larger comparative studies are
      necessary to establish the real impact of this therapeutic approach.

PMID- 22460097
TI  - Expression of cyclooxygenase-2 (COX-2) in pituitary tumours.
AB  - BACKGROUND: Microvessel density in angiogenesis is regarded as a prognostic
      factor of tumour invasiveness, independent of cell proliferation. In recent
      studies of pituitary tumours, correlation between the expression of
      cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel
      surface density has been established. We studied the expression of COX-2 in
      different types of pituitary adenomas to determine the usefulness of COX-2
      expression as a prognostic factor of tumour progression or recurrence in patients
      with hypophyseal tumours. MATERIAL/METHODS: We retrospectively studied a group of
      60 patients of mean age 46.7+/-17.6 (range, 18 to 85) years who underwent
      pituitary tumour surgery. Expression of COX-2, as determined by
      immunohistochemistry, was analyzed in relation to histopathology features of
      tumour, clinical symptoms, MR imaging and post-operative recurrence/progression
      of disease. RESULTS: COX-2 was expressed in adenomas of 87% of patients, with a
      median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in
      hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We
      found no differences in COX-2 expression with respect to patient age, gender,
      tumour size, degree of tumour invasiveness, or whether tumours were
      immunopositive or immunonegative for pituitary hormones, nor have we found any
      relation between COX-2 expression and recurrence or progression of tumour size.
      CONCLUSIONS: COX-2 does not appear to be a predictive factor for recurrence or
      progression of tumour size. Nevertheless, due to the observed relatively high
      expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors
      are justified in these tumours.

PMID- 22460098
TI  - Transdermal estradiol in castrate and chemotherapy resistant prostate cancer.
AB  - BACKGROUND: Given prior studies demonstrating the marked clinical activity of
      oral estrogens in prostate cancer, more recent data demonstrating the safety of
      transdermal estradiol, and the renewed interest in targeting testosterone
      metabolism and androgen receptor pathways, we report the results of a trial of
      transdermal estradiol in advanced heavily pre-treated castrate and chemotherapy
      refractory patients. MATERIAL/METHODS: Patients with prostate cancer progressing
      after androgen ablation therapy and chemotherapy were treated with transdermal
      estradiol patches (0.4 mg per 24 hours total) applied weekly and assessed for
      tolerability and biochemical activity. RESULTS: Twenty-two patients were treated
      on study with all patients evaluable for safety and 20 patients evaluable for
      response. All patients had aggressive and resistant disease, as demonstrated by a
      median PSA of 170 ng/mL (range 14 to 5030 ng/mL), with more than 60% having been
      treated with two or more prior chemotherapy regimens, and 20% with visceral
      disease. Nine patients had a decrease in PSA, of which two patients had a PSA
      response defined as a decline in PSA by 50%. Therapy was well tolerated and no
      thrombotic events were observed. CONCLUSIONS: In heavily pre-treated patients
      with advanced castrate and chemotherapy refractory metastatic prostate cancer,
      transdermal estradiol was safe and had biochemical activity. These data support
      further studies to understand if transdermal estradiol can be useful following
      multiple standard therapies.

PMID- 22460099
TI  - Salvage surgery of recurrence after laryngectomy--when should the alt free flap
      be modified?
AB  - BACKGROUND: Reconstruction of the pharynx and cervical esophagus has
      significantly progressed in the last 2 decades. A revolution in microvascular
      surgery has provided numerous choices for primary restoration, or in secondary
      reconstructions necessary for recurrences or complications of primary surgery.
      The goals of reconstruction after laryngopharyngoesophagectomy are to provide
      continuity of the alimentary tract, to protect major blood vessels, to heal the
      primary wound, and to restore the swallowing and breathing functions with minimal
      donor site and neck morbidity and deformation. CASE REPORT: We present 3 cases
      with complex defects of the laryngopharynx, cervical esophagus and trachea and
      anterior neck skin following central neck exenteration safely reconstructed with
      a single anterolateral thigh flap. No postoperative complications occurred in any
      of the 3 cases of reconstructions, each using a single anterolateral thigh flap.
      CONCLUSIONS: This approach significantly simplified the reconstruction, with
      quick recovery, short hospital stay and excellent functional and aesthetic
      results.

PMID- 22460100
TI  - A novel asymmetric-loop molecular beacon-based two-phase hybridization assay for
      accurate and high-throughput detection of multiple drug resistance-conferring
      point mutations in Mycobacterium tuberculosis.
AB  - The accurate and high-throughput detection of drug resistance-related multiple
      point mutations remains a challenge. Although the combination of molecular
      beacons with bio-immobilization technology, such as microarray, is promising, its
      application is difficult due to the ineffective immobilization of molecular
      beacons on the chip surface. Here, we propose a novel asymmetric-loop molecular
      beacon in which the loop consists of 2 parts. One is complementary to a target,
      while the other is complementary to an oligonucleotide probe immobilized on the
      chip surface. With this novel probe, a two-phase hybridization assay can be used
      for simultaneously detecting multiple point mutations. This assay will have
      advantages, such as easy probe availability, multiplex detection, low background,
      and high-efficiency hybridization, and may provide a new avenue for the
      immobilization of molecular beacons and high-throughput detection of point
      mutations.

PMID- 22460101
TI  - Alteration of distortion product otoacoustic emission input/output functions in
      subjects with a previous history of middle ear dysfunction.
AB  - BACKGROUND: The aim of this study was to investigate the effects of sub-clinical
      alterations on the amplitudes and slopes of the DPOAE input-output responses from
      subjects with previous history of middle ear dysfunction. MATERIAL/METHODS: The
      study included 15 subjects with and 15 subjects without a history of otitis media
      in the last 10 years. All participants were assessed with acoustic immittance,
      pure-tone audiometry, and DPOAEs. For the later, I/O functions and I/O slopes
      were estimated at 1501, 2002, 3174, 4004 and 6384 Hz. RESULTS: No statistically
      significant differences were found between the 2 groups in terms of behavioral
      thresholds. The group with a previous history of middle ear dysfunction presented
      significantly lower mean DPOAE amplitudes at 2002, 3174 and 4004 Hz. In terms of
      DPOAE slopes, no statistically significant differences were observed at the
      tested frequencies, except at 3174 Hz. CONCLUSIONS: Middle ear pathologies can
      produce subclinical alterations that are undetectable with traditional pure-tone
      audiometry. The data from the present study show that reduced amplitude DPOAEs
      are associated with a previous history of middle ear complications. The
      corresponding DPOAE slopes were affected at only 1 tested frequency, suggesting
      that the cochlear non-linearity is preserved. Considering these results, it
      remains to be elucidated to what degree the DPOAE amplitude attenuation
      interferes with higher-order auditory tasks.

PMID- 22460102
TI  - Intraregional differences in asthma prevalence and risk factors for asthma among
      adolescents in Split-Dalmatia County, Croatia.
AB  - BACKGROUND: Our aim was to assess the differences in intraregional prevalence of
      asthma in adolescents in Split-Dalmatia County to determine asthma risk factors
      in our population and estimate the specificity and sensitivity of the
      questionnaire used. MATERIAL/METHODS: We conducted the study using the European
      Community Respiratory Health Survey II short questionnaire supplemented by some
      questions from the International Study of Asthma in Childhood questionnaire. The
      participants suspected to have asthma were invited for examination by an asthma
      specialist who established the final diagnosis of asthma according to the medical
      history, physical examination, skin-prick tests, and peak flow measurements.
      RESULTS: A total of 4027 students (51.2% male) participated in the study.
      According to the prevalence of wheezing during the last 12 months, asthma
      prevalence was estimated at 9.7%. The total prevalence of asthma confirmed by an
      asthma specialist in the selected population was 5.60% (95% CI, 4.93-6.36%);
      6.18% in Split (95% CI, 5.37-7.09), 5.63% in Imotski (95% CI, 3.48-8.58), and
      2.90% in Sinj (95% CI, 1.67-4.68) (P=0.0028). We found sensitization to
      aeroallergens and peanuts, and active smoking to be independent risk factors for
      asthma. CONCLUSIONS: Split-Dalmatia County has moderate asthma prevalence, with a
      significant intraregional difference. Asthma prevalence estimated by a
      questionnaire (9.7%) overestimates the prevalence of asthma confirmed by an
      asthma specialist (5.6%) in adolescents in Croatia. Our data confirmed the need
      of a more complex questionnaire to evaluate the accurate prevalence of current
      asthma or the need for subsequent clinical evaluation of the questionnaire
      obtained data. Allergic sensitization to aeroallergens and active smoking were
      important risk factors for asthma.

PMID- 22460103
TI  - The poor oral health status of former heroin users treated with methadone in a
      Chinese city.
AB  - BACKGROUND: There have been few studies conducted on the oral health status of
      illegal drug users in China, affecting the development of preventive and
      therapeutic approaches. The aim of the present study was to investigate and
      analyze the oral health status of former heroin users treated with methadone in
      Chengdu, the capital of Sichuan Province in southwestern China. MATERIAL/METHODS:
      The presence of caries (decayed tooth and root), missing teeth, residual roots,
      dental prosthetic restoration and periodontal health were investigated in 445
      former heroin users treated with methadone (317 males and 128 females). Their
      ages ranged from 20 to 59 years old. RESULTS: Among the study subjects, the
      prevalence of decayed/filled teeth was 64.72%, and the mean of decayed/filled
      teeth score was 2.92. The prevalence of decayed/filled roots was 21.80%, and the
      mean of decayed/filled roots score was 0.62. The prevalence of missing teeth was
      31.46%, and the mean missing teeth score was 0.62. The prevalence of residual
      roots was 42.02%, with a mean score of 1.06. The rates of gingival bleeding,
      calculus, shallow pockets periodontal pocket, and deep periodontal pocket were
      99.55%, 96.63%, 30.34%, and 2.70%, respectively. CONCLUSIONS: The oral health
      status among the studied former heroin users in Chengdu was poorer than the
      general population. Better dental care for the former heroin users is needed to
      promote their oral health.

PMID- 22460104
TI  - Treatment of pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a chronic progressive disease of the
      pulmonary vasculature characterized by elevated pulmonary arterial pressure and
      secondary right ventricular failure. PAH is considered a life-threatening
      condition unless treated. This article provides a comprehensive review of
      controlled and uncontrolled trials to define the risk-benefit for different
      therapeutic options of this clinical disorder. Relevant published articles were
      identified through searches of the National Center for Biotechnology PubMed
      database. All therapeutic measures for PAH were discussed. Six drugs have been
      approved in the United States for the treatment of PAH. Extensive medical
      advancement has been achieved in treatment of PAH. However, none of the approved
      therapies have shown ability to cure the disease. New research should be
      performed to develop promising new therapies.

PMID- 22460106
TI  - Treatment of Gustilo grade III tibial fractures with unreamed intramedullary
      nailing versus external fixator: a meta-analysis.
AB  - Unreamed Intramedullary nailing and external fixation are 2 major treatments
      widely used in Gustilo grade III open tibial fractures, but the difference in
      effectiveness and complication remains controversial. We retrieved original
      publications of comparative studies from medical literature databases and
      selected 9 of them for a meta-analysis. Observation items include malunion and
      deep infection rate, non-union and comparison of time to union. The analysis
      showed a lower malunion rate using unreamed intramedullary nailing than external
      fixation. No significant differences were revealed in deep infection/nonunion
      rate and time to union. More studies of larger scale and better design are needed
      to reach an ultimate and definite conclusion.

PMID- 22460107
TI  - Prevention of communication disorders--screening pre-school and school-age
      children for problems with hearing, vision and speech: European Consensus
      Statement.
AB  - BACKGROUND: Communication is an integral part of human behaviour. Communication
      disorders are associated mainly with impairment in hearing, vision, and/or
      speech, which influences the ability to receive, comprehend, produce, and express
      verbal, nonverbal, and graphic information. When unrecognized and unmanaged,
      these very often "invisible" conditions can have a significant detrimental effect
      on a child's development, affecting educational, social, and psychological
      progress. MATERIAL/METHODS: A panel of experts discussed the screening of pre
      school and school-age children for problems with hearing, vision, and speech
      during the 10th Congress of the European Federation of Audiology Societies
      (EFAS), held in Warsaw, Poland, on 22 June, 2011. RESULTS: The European Consensus
      Statement on Hearing, Vision, and Speech Screening in Pre-School and School-Age
      Children was the result of the scientific discussions. It was endorsed by experts
      in audiology, otolaryngology, phoniatry, ophthalmology, and speech language
      pathology from throughout Europe. Key elements of the consensus, as described
      herein, are: 1) defining the role of screening programmes in the identification
      and treatment of communication disorders; 2) identifying the target population;
      3) promoting general awareness about the consequences of communication disorders;
      4) recognizing the need for a quality control system in screening programmes; 5)
      encouraging cooperation among European countries to provide a high level of
      public health services for the prevention, identification, and treatment of
      communication disorders. CONCLUSIONS: The European Consensus Statement on
      Hearing, Vision, and Speech Screening in Pre-School and School-Age Children will
      encourage the appropriate authorities of the various countries involved to
      initiate screening for communication disorders in pre-school and school-age
      children.

PMID- 22460105
TI  - Dietary and botanical anxiolytics.
AB  - Drugs used to treat anxiety have many negative side effects including addiction,
      depression, suicide, seizures, sexual dysfunction, headaches and more. Anxiolytic
      medications do not restore normal levels of neurotransmitters but instead
      manipulate the brain chemistry. For example, selective serotonin reuptake
      inhibitors (SSRIs) prevent the reuptake of serotonin from the synapse allowing
      serotonin to remain in the area of activity for a longer period of time but does
      not correct the lack of serotonin production. Benzodiazepines, such as Valium and
      Xanax(r), stimulate GABA receptors, thus mimicking the calming effects of GABA
      but again do not fix the lack of GABA production. Often, the brain becomes
      accustomed to these medications and they often lose their effectiveness,
      requiring higher doses or different drugs. In contrast to anxiolytic drugs, there
      are herbs and nutrients which can stimulates neurotransmitter synthesis and more
      naturally effect and even adjust brain chemistry in the absence of many of the
      side effects experienced with drugs. Therefore this paper explores several herbal
      and nutritional approaches to the treatment of anxiety.

PMID- 22460108
TI  - Analysis of the causes of medical evacuation of injured and sick soldiers of the
      Polish Military Contingent in the Islamic State of Afghanistan taking part in
      International Security Assistance Force operations.
AB  - BACKGROUND: Military casualties in Afghanistan arise in part from climatic and
      natural conditions that are difficult for European soldiers to endure, as well as
      from intense guerrilla combat with mass use of IEDs (improvised explosive
      devices), thus posing numerous and diverse medical problems requiring evacuation
      to the home country. A search of the literature revealed no comprehensive studies
      of the causes of medical evacuation from this theater of operations.
      MATERIAL/METHODS: This article is a review of medical reports of the Polish
      Military Contingent taking part in Operation Enduring Freedom during the period
      from 01 January 2010 to 31 December 2011, including an analysis of causes of all
      ROLE 4 medical evacuations (to the military base in Germany or to the home
      country). RESULTS: As many as 565 (5.49%) of the total of 10 294 contingent
      soldiers were evacuated during the analyzed period. Of these, 29% of evacuation
      cases were due to combat injuries, 23% to complications of respiratory tract
      infection, 11% to mental health problems, 11% to chronic neuralgias, 12% to
      complications of acute gastrointestinal infections, 4% to non-combat injuries, 3%
      to dental and maxillofacial problems, 2% to dermatological problems and 2% to
      leishmaniasis. The remaining causes included chronic organic/systemic diseases
      manifested during service. CONCLUSIONS: The main causes of medical evacuations to
      the home country were the consequences of combat injuries, mainly due to IED
      attacks. Appropriate diagnosis and early treatment of infections is also an
      important problem in the face of a significant number of complications resulting
      in evacuation of soldiers to their home country.

PMID- 22460109
TI  - Defining rewardable innovation in drug therapy.
AB  - Implementing mechanisms for rewarding those who introduce innovative medicinal
      products requires a definition of 'rewardable innovation'. Here, we propose a
      definition of innovation with respect to medicinal products, accompanied by a
      ranking of the importance of different types of innovativeness, with the aim of
      providing a basis for rewarding such innovation.

PMID- 22460110
TI  - Unleashing the mini-sentinel.

PMID- 22460111
TI  - Hedgehog inhibitor gets landmark skin cancer approval, but questions remain for
      wider potential.

PMID- 22460113
TI  - Deal watch: Biogen acquires Stromedix to pursue novel fibrosis therapy.

PMID- 22460114
TI  - Market watch: Upcoming market catalysts in Q2 2012.

PMID- 22460116
TI  - Trevor Mundel. Interview by Asher Mullard.

PMID- 22460117
TI  - Rare diseases and orphan drugs.

PMID- 22460118
TI  - Aflibercept.
AB  - In November 2011, aflibercept (Eylea; Regeneron Pharmaceuticals), a recombinant
      fusion protein that binds to members of the vascular endothelial growth factor
      family, was approved by the US Food and Drug Administration (FDA) for the
      treatment of patients with neovascular age-related macular degeneration.

PMID- 22460119
TI  - Neurodegenerative disease: RXR agonist reverses Alzheimer's disease.

PMID- 22460120
TI  - Stroke: Can PSD95 inhibitors widen the therapeutic window?

PMID- 22460121
TI  - Metabolic disease: Identifying novel targets of resveratrol.

PMID- 22460122
TI  - Novel molecular targets for atrial fibrillation therapy.
AB  - Atrial fibrillation is the most common type of cardiac arrhythmia, and is
      responsible for substantial morbidity and mortality in the general population.
      Current treatments have moderate efficacy and considerable risks, especially of
      pro-arrhythmia, highlighting the need for new therapeutic strategies. In recent
      years, substantial efforts have been invested in developing novel treatments that
      target the underlying molecular determinants of atrial fibrillation, and several
      new compounds are under development. This Review focuses on the mechanistic
      rationale for the development of new anti-atrial fibrillation drugs, on the
      molecular and structural motifs that they target and on the results obtained so
      far in experimental and clinical studies.

PMID- 22460126
TI  - Role of sex hormones in modulation of brown adipose tissue activity.
AB  - The recent demonstration that metabolically active brown adipose tissue (BAT) is
      present with a high prevalence in humans undoubtedly represents one of the major
      advancements in the field of metabolic research in the last few years. The
      increasing interest in BAT is justified by preclinical observations highlighting
      an important role of this tissue in energy dissipation and metabolic clearance of
      substrates from the blood. These findings imply that stimulation of BAT activity
      may represent a new therapeutic approach for obesity and associated
      comorbidities. However, before proposing BAT as a target organ for therapeutics
      in a clinical setting, many further notions about BAT function and modulation
      need to be explored. Keeping in mind the importance of sex dimorphism in energy
      metabolism control under physiological and pathological conditions, sex hormones
      may play a relevant role in the regulation of BAT activity in both males and
      females. Much of the evidence acquired in the past supports the concept of an
      important role for different sex hormones in BAT thermogenesis and indicates that
      this tissue mediates the ability of sex hormones to modulate energy balance.
      These findings make it plausible that a modified interaction between BAT and sex
      hormones may contribute to the development and the maintenance of obesity and
      associated metabolic complications.

PMID- 22460125
TI  - Identification of ING4 (inhibitor of growth 4) as a modulator of docetaxel
      sensitivity in human lung adenocarcinoma.
AB  - Resistance to docetaxel (DTX) usually occurs in patients with lung
      adenocarcinoma. To better elucidate the underlying molecular mechanisms involved
      in resistance to DTX-based chemotherapy, we established a DTX-resistant lung
      adenocarcinoma cell line (SPC-A1/DTX). By gene array analysis, the expression of
      ING4 was found to be significantly downregulated in SPC-A1/DTX cells.
      Additionally, the decreased expression of the ING4 gene was induced upon DTX
      treatment of SPC-A1 cells. Overexpression of ING4 reverses DTX or paclitaxel
      resistance of DTX-resistant lung adenocarcinoma cells (SPC-A1/DTX or A549/Taxol)
      by inducing apoptosis enhancement and G2/M arrest, and small interfering RNA
      mediated ING4 knockdown renders DTX-sensitive lung adenocarcinoma cells more
      resistant to DTX or paclitaxel. Also, overexpression of ING4 could enhance the in
      vivo sensitivity of SPC-A1/DTX cells to DTX. The phenotypical changes of SPC
      A1/DTX cells induced by overexpression of ING4 might be associated with the
      decreased ratio of Bcl-2/Bax, which resulted in the activation of caspase-3. The
      level of ING4 expression in tumors of nonresponding patients was significantly
      lower than that in those of responders, suggesting that the expression of ING4
      was positively correlated with tumor response to DTX. Our results provide the
      first evidence that ING4 might be essential for DTX resistance in lung
      adenocarcinoma. Thus, ING4 will be a potential molecular target for overcoming
      resistance to DTX-based chemotherapies in lung adenocarcinoma.

PMID- 22460124
TI  - Fc receptor-targeted therapies for the treatment of inflammation, cancer and
      beyond.
AB  - The direct or indirect targeting of antibody Fc receptors (FcRs) presents unique
      opportunities and interesting challenges for the treatment of inflammatory
      diseases, cancer and infection. Biological responses induced via the Fc portions
      of antibodies are powerful, complex and unusual, and comprise both activating and
      inhibitory effects. These properties can be exploited in the engineering of
      therapeutic monoclonal antibodies to improve their activity in vivo. FcRs have
      also emerged as key participants in the pathogenesis of several important
      autoimmune diseases, including systemic lupus erythematosus and rheumatoid
      arthritis. Therapeutic approaches based on antagonizing FcR function with small
      molecules or biological drugs such as monoclonal antibodies and recombinant
      soluble FcR ectodomains have gained momentum. This Review addresses various
      strategies to manipulate FcR function to overcome immune complex-mediated
      inflammatory diseases, and considers approaches to improve antibody-based
      anticancer therapies.

PMID- 22460128
TI  - A stereodynamic and redox-switchable encapsulation-complex containing a copper
      ion held by a tris-quinolinyl basket.
AB  - We investigated the coordination of Cu(I)/Cu(II) ions to chiral basket (S(3))-1.
      The results of both experimental and computational studies suggest the formation
      of a copper redox-switchable system capable of entrapping CH(3)CN.

PMID- 22460123
TI  - Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate
      pain.
AB  - Chronic pain remains unsatisfactorily treated, and few novel painkillers have
      reached the market in the past century. Increasing the levels of the main
      endogenous opioid peptides - enkephalins - by inhibiting their two inactivating
      ectopeptidases, neprilysin and aminopeptidase N, has analgesic effects in various
      models of inflammatory and neuropathic pain. Stemming from the same
      pharmacological concept, fatty acid amide hydrolase (FAAH) inhibitors have also
      been found to have analgesic effects in pain models by preventing the breakdown
      of endogenous cannabinoids. Dual enkephalinase inhibitors and FAAH inhibitors are
      now in early-stage clinical trials. In this Review, we compare the effects of
      these two potential classes of novel analgesics and describe the progress in
      their rational design. We also consider the challenges in their clinical
      development and opportunities for combination therapies.

PMID- 22460129
TI  - Prevalence and characteristics of psychotic-like experiences in Kenyan youth.
AB  - Current evidence suggests that there may be significant differences in psychotic
      symptom prevalence in Africa compared with other cultures. However, there have
      been few studies evaluating these symptoms in the continent. We conducted a cross
      sectional survey of psychotic-like experiences (PLEs) in 2963 Kenyan students
      from seven tertiary academic institutions spread across Kenya, using a self
      administered psychosis questionnaire evaluating psychotic experiences and
      demographic variables. Logistic regression was used to evaluate relationship
      between PLEs and demographic variables. Latent class analysis (LCA) was used to
      determine specific classes of psychotic experiences. Twenty-three percent of
      respondents reported having at least one PLE, and 19% reported this unrelated to
      drug use or sleep. Compared to students identifying as Protestant Christians,
      Catholics had a lower likelihood of having any PLE or visual hallucinations.
      Other demographic variables were not significantly associated with PLEs. LCA of
      PLEs resulted in a three-class model that comprised 1) a non-psychotic class
      (83.8%), 2) a predominantly hallucinatory class ("type I PLE"; 12.7%), and 3) a
      multiple symptom class ("type II PLE"; 3.5%). Both psychotic classes had a
      predominance of male students. Further studies are required to clarify
      functionality and clinical progression associated with observed patterns of
      psychosis, as well as the generalizability of our findings.

PMID- 22460130
TI  - Electrophysiological evidence for primary semantic memory functional organization
      deficits in schizophrenia.
AB  - N400, an event-related brain potential (ERP) waveform elicited by meaningful
      stimuli, is normally reduced by stimulus repetition (N400 repetition priming),
      and relatedness between the eliciting stimulus and preceding ones (relatedness
      priming). Schizophrenia patients' N400 relatedness priming deficits suggest
      impairment in using meaningful prime stimuli to facilitate processing of related
      concepts in semantic memory. To examine whether this deficiency arises from
      difficulty activating the prime concept per se, as indexed by reduced N400
      repetition priming; or from impaired functional connections among concepts in
      semantic memory, as reflected by reduced relatedness priming but normal
      repetition priming; we recorded ERPs from 16 schizophrenia patients and 16
      controls who viewed prime words each followed at 300- or 750-ms stimulus-onset
      asynchrony (SOA) by an unrelated, related or repeated target word, or a nonword,
      in a lexical-decision task. In both groups, N400s were largest (most negative)
      for unrelated, intermediate for related, and smallest for repeated targets.
      Schizophrenia patients exhibited subnormal N400 relatedness priming at the 300-ms
      SOA, but normal repetition priming at both SOAs, suggesting that their impairment
      in using prime words to activate related concepts results from abnormal
      functional connections among concepts within semantic memory, rather than
      inability to activate the prime concept itself.

PMID- 22460131
TI  - Theory of mind, severity of autistic symptoms and parental correlates in children
      and adolescents with Asperger syndrome.
AB  - This study addresses the theory of mind (ToM) ability of Asperger's syndrome/high
      functioning autism (AS/HFA) children and their parents and the severity of the
      autistic symptoms. Fifty-three families, each consisting of a mother, father and
      a child, participated in this study (N=159). The 53 children in the sample
      included 25 children diagnosed with AS/HFA and 28 typically developing (TD)
      children. The Social Attribution Task (SAT) and tests assessing autistic symptoms
      were used. AS/HFA children had lower scores than TD children on three of the SAT
      indices (Person, ToM Affective, and Salience). Fathers of AS/HFA children did not
      have lower scores than fathers of TD children on the SAT task, whereas mothers of
      AS/HFA children had lower scores on the Person index, a pattern similar to seen
      in their children, suggesting a possible genetic contribution of mothers to ToM
      deficit in AS/HFA children.

PMID- 22460133
TI  - Bias to negative emotions: a depression state-dependent marker in adolescent
      major depressive disorder.
AB  - The aim of the current research was to examine for the first time the extent to
      which bias to negative emotions in an inhibitory control paradigm is a state or
      trait marker in major depressive disorder (MDD) in adolescents. We administered
      the affective go/no go task which measures the ability to switch attention to or
      away from positive or negative emotional stimuli to 40 adolescents with MDD (20
      in acute episode (MDDa) and 20 in remission (MDDr)) and 17 healthy controls (HC).
      MDDa were significantly faster on the shift to negative target blocks as compared
      to shift to positive target blocks while HC and MDDr displayed the opposite
      pattern as measured by an "emotional bias index" (EBI=latency (shift to negative
      targets)-latency (shift to positive targets)). There was also a trend for an
      effect of group on commission errors, suggesting more impulsive responding by
      MDDa than both MDDr and HC independently of stimulus valence throughout the task.
      Negative bias was not associated with depression severity or medication status.
      In conclusion, bias to negative emotional stimuli appears to be present in the
      acute stage of MDD and absent in remission suggesting that it is a depression
      state-specific marker of MDD in adolescents. Latency emerges as a better proxy of
      negative bias than commission errors and accuracy on this inhibitory control task
      in adolescents with MDD.

PMID- 22460134
TI  - Multifrequency inversion in magnetic resonance elastography.
AB  - Time-harmonic shear wave elastography is capable of measuring viscoelastic
      parameters in living tissue. However, finite tissue boundaries and waveguide
      effects give rise to wave interferences which are not accounted for by standard
      elasticity reconstruction methods. Furthermore, the viscoelasticity of tissue
      causes dispersion of the complex shear modulus, rendering the recovered moduli
      frequency dependent. Therefore, we here propose the use of multifrequency wave
      data from magnetic resonance elastography (MRE) for solving the inverse problem
      of viscoelasticity reconstruction by an algebraic least-squares solution based on
      the springpot model. Advantages of the method are twofold: (i) amplitude nulls
      appearing in single-frequency standing wave patterns are mitigated and (ii) the
      dispersion of storage and loss modulus with drive frequency is taken into account
      by the inversion procedure, thereby avoiding subsequent model fitting. As a
      result, multifrequency inversion produces fewer artifacts in the viscoelastic
      parameter map than standard single-frequency parameter recovery and may thus
      support image-based viscoelasticity measurement. The feasibility of the method is
      demonstrated by simulated wave data and MRE experiments on a phantom and in vivo
      human brain. Implemented as a clinical method, multifrequency inversion may
      improve the diagnostic value of time-harmonic MRE in a large variety of
      applications.

PMID- 22460132
TI  - Association study of early-immediate genes in childhood-onset mood disorders and
      suicide attempt.
AB  - Childhood-onset mood disorders (COMD) are serious affective disorders with
      deleterious developmental sequelae including interpersonal dysfunction, psychotic
      symptoms and suicidal behavior. The current study examines 10 markers from two
      early-immediate genes for association with COMD and suicide attempt (SA) - HOMER1
      and human neuronal pentraxin II (NPTX2). We examined individuals diagnosed with
      COMD versus matched controls, as well as individuals with COMD and a history of
      at least one lifetime SA versus COMD participants with no history of SA. No
      significant genotypic association was noted between any of the single nucleotide
      polymorphisms (SNPs) and COMD. Our sample yielded a nominally significant allelic
      association between the HOMER1 rs7713917 SNP and COMD. We report significant
      genotype associations between HOMER1 rs2290639 and SA , and between NPTX2 markers
      rs705315 and rs1681248 and SA, findings that remained statistically significant
      after multiple test correction. A three-way interaction was observed among HOMER1
      rs4704560, rs2290639 and NPTX2 rs705318. The associations we describe for HOMER1
      and NPTX2 with SA should be considered preliminary until replicated.

PMID- 22460135
TI  - Advances in targeted therapies XIII.

PMID- 22460136
TI  - IL-33: a Janus cytokine.
AB  - Interleukin (IL) 33, a member of the IL-1 family, is the ligand of ST2 that is
      expressed mainly on activated Th2 cells and mast cells. IL-33 can skew a
      predominantly Th1 cell population to a mainly Th2 cells phenotype in vivo. IL-33
      messenger RNA is expressed early during infection of the intestinal-dwelling
      nematode Trichuris muris in mice. IL-33 treatment enhances resistance to
      Trichuris infection. IL-33 also effectively attenuates sepsis by mobilising the
      innate cells, neutrophils, to the site of infection, helping to clear the
      pathogens. Thus, IL-33 may be evolutionally preserved for the host defence
      against infections. IL-33 can reduce an ongoing atherosclerosis in ApoE(-/-) mice
      and attenuate adipocytes mainly by inducing the production of type II cytokines.
      In contrast, IL-33 can also exacerbate allergy and the inflammation in collagen
      induced or serum-induced arthritis. Hence, IL-33 is a double-edged sword, and
      targeting IL-33 should be approached with caution.

PMID- 22460137
TI  - Updated consensus statement on biological agents for the treatment of rheumatic
      diseases, 2011.

PMID- 22460138
TI  - HDAC inhibitor therapy in autoimmunity and transplantation.
AB  - Pharmacological inhibitors of histone/protein deacetylases (HDACi) have
      considerable therapeutic potential as anti-inflammatory and immunosuppressive
      drugs. The utility of HDACi as anti-inflammatory agents is dependent upon their
      proving safe and effective in experimental models. Current pan-HDACi compounds
      are ill-suited to this role, given the broad distribution of target HDACs and
      their complex and multifaceted mechanisms of action. By contrast, the development
      of isoform-selective HDACi may provide important new tools for treatment in
      autoimmunity and transplantation. This review discusses which HDACs are
      worthwhile targets in inflammation, and the progress made towards their
      therapeutic inhibition, including the use of HDAC subclass and isoform-selective
      HDACi to promote the functions of Foxp3+ T-regulatory cells.

PMID- 22460139
TI  - TNF and EPO: major players in the innate immune response: their discovery.

PMID- 22460140
TI  - Leishmaniasis in rheumatology, haematology and oncology: epidemiological,
      immunological and clinical aspects and caveats.
AB  - Leishmaniasis is an intracellular protozoan infection that can lead to cutaneous,
      mucocutaneous, visceral or systemic manifestations depending on the parasite
      species and virulence and on the host immune response. It is endemic in countries
      of Europe (Mediterranean basin), Asia, Africa, Central and South America, but
      autochthonous cases begin to emerge outside classical disease areas. CD4+ T
      helper cells, interferon gamma, dendritic cells and macrophages are the key
      components of antileishmanial defence. Leishmaniasis is an important differential
      diagnosis in patients with chronic lesions of the skin or mucous membranes or
      with fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, histocytosis,
      haemophagocytic syndrome or glomerulonephritis. Organ transplant recipients and
      patients with autoimmune syndromes are at particular risk of developing visceral
      leishmaniasis following immunosuppressive therapy (eg, with steroids,
      methotrexate, ciclosporin or tumour necrosis factor-neutralising biological
      agents). Diagnosis and adequate treatment of leishmaniasis requires the combined
      use of culture, microscopic and nucleic acid amplication methods and species
      identification by sequencing and other molecular techniques. Standard regimens
      for the treatment of visceral leishmaniasis are intravenous liposomal
      amphotericin B (3 mg/kg body weight for 10 days) or oral miltefosine (150 mg/day
      for 28 days).

PMID- 22460141
TI  - How do contemporary imaging techniques contribute to basic and clinical
      rheumatology?
AB  - Recent major advances in biomedical imaging techniques have allowed us to
      visualise a variety of previously unseen biological phenomena. In particular,
      advanced fluorescent microscopy and radioimaging have enabled us to visualise
      cellular and molecular dynamics in living animals and humans. These new
      technologies have identified novel therapeutic targets against a wide array of
      diseases and have provided novel diagnostic tools for the evaluation of several
      disease conditions. In this brief review, the author outlines the contemporary
      imaging techniques used in the fields of immunology and rheumatology, with
      special focus on intravital fluorescent microscopy, and discusses how these
      cutting-edge methodologies contribute to clinical practice for patients with
      rheumatism.

PMID- 22460142
TI  - In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis.
AB  - Multiple cytokines play a pivotal role in the pathogenesis of rheumatoid
      arthritis (RA). The appropriate intracellular signalling pathways must be
      activated via cytokine receptors on the cell surface, and the tyrosine kinases
      transduce the first 'outside to in' signals to be phosphorylated after receptor
      binding to its ligand. Among them, members of the Janus kinase (JAK) family are
      essential for the signalling pathways of various cytokines and are implicated in
      the pathogenesis of RA. The in vitro, ex vivo and in vivo effects of a JAK
      inhibitor CP-690,550 (tofacitinib) for the treatment of RA are reported. In vitro
      experiments indicated that the effects of tofacitinib were mediated through
      suppression of interleukin 17 (IL-17) and interferon gamma production and
      proliferation of CD4 T cells, presumably Th1 and Th17. A treatment study was
      conducted in the severe combined immunodeficiency (SCID)-HuRAg mice, an RA animal
      model using SCID mice implanted with synovium and cartilage from patients.
      Tofacitinib reduced serum levels of human IL-6 and IL-8 in the mice and also
      reduced synovial inflammation and invasion into the implanted cartilage. A phase
      2 double-blind study using tofacitinib was carried out in Japanese patients with
      active RA and inadequate response to methotrexate (MTX). A total of 140 patients
      were randomised to tofacitinib 1, 3, 5, 10 mg or placebo twice daily and the
      American College of Rheumatology 20% improvement criteria (ACR20) response rate
      at week 12, a primary end point, was significant for all tofacitinib treatment
      groups. Thus, an orally available tofacitinib in combination with MTX was
      efficacious and had a manageable safety profile. Tofacitinib at 5 and 10 mg twice
      a day appears suitable for further evaluation to optimise the treatment of RA.

PMID- 22460143
TI  - Antisense oligonucleotide mediated exon skipping as a potential strategy for the
      treatment of a variety of inflammatory diseases such as rheumatoid arthritis.

PMID- 22460144
TI  - CD3 zeta defects in systemic lupus erythematosus.
AB  - The prototype autoimmune disease, systemic lupus erythematosus (SLE), has been
      known to be associated with deficiency of zeta chain, a component of the T-cell
      receptor-CD3 complex. Comprehensive analysis has shown that expression of the CD3
      zeta chain is attenuated or absent in over half of SLE patients. Furthermore,
      aberrant transcripts of the CD3 zeta chain, including spliced variants lacking
      exon 7 or having a short 3'-untranslated region, have been detected in SLE T
      cells. Although attenuated expression of the CD3 zeta chain is also observed in
      cancer patients, infections and other autoimmune diseases, sustained attenuation
      of the CD3 zeta expression accompanied with aberrant transcripts are only
      observed in SLE. In this study, the authors review the unique features of CD3
      zeta defects observed in SLE and discuss the molecular basis of the defects by
      recent findings in animal models, single-nucleotide polymorphisms and genome-wide
      association studies.

PMID- 22460145
TI  - New approaches to the assessment and treatment of the idiopathic inflammatory
      myopathies.
AB  - The rarity and heterogeneity of the idiopathic inflammatory myopathies (IIM), and
      the few validated assessment tools available, have limited information to guide
      the management of patients with polymyositis, dermatomyositis or inclusion body
      myositis. In light of the need for such tools, the International Myositis
      Assessment and Clinical Studies Group (IMACS) was formed as a multidisciplinary
      consortium of rheumatologists, neurologists, dermatologists, physiatrists and
      other myositis experts to develop consensus and standards for the conduct and
      reporting of myositis studies, and to facilitate myositis research. IMACS has
      developed consensus core set measures of disease activity, disease damage and
      patient-reported outcomes, and compiled a preliminary definition of improvement.
      The IMACS tools assist in the evaluation of the extent of disease activity and
      damage, although other approaches--including key clinical features, laboratory
      tests, muscle T1 and short tau inversion recovery MRI and immunological markers-
      are also helpful. Clinical remission is a realistic objective for most patients
      and should be pursued aggressively to optimise outcomes. Physical therapy and
      rehabilitation should be applied early and consistently to achieve optimal
      strength and function. Treatments that have been developed for other immune
      mediated diseases are also being used and tested in the IIM, and some have shown
      anecdotal evidence of benefit. Recent advances in understanding the pathogenesis
      of myositis, development of assessments and treatments for other diseases that
      can be applied to myositis, and international collaborations and consensus
      standards for evaluating the IIM, all promise improvements in the assessment and
      treatment of myositis in the future.

PMID- 22460146
TI  - Defining remission in rheumatoid arthritis.
AB  - OBJECTIVE: Given the inconsistency of remission definitions in rheumatoid
      arthritis (RA) trials, the goal of this American College of Rheumatology/European
      League Against Rheumatism committee was to define remission. METHODS: The
      committee instructed a working group that a new remission definition, among other
      requirements, needed to allow for little, if any, active clinical disease and to
      be defined using the core set of outcome measures for RA trials and that those in
      remission at one time needed to have a low risk of later worsening function or
      radiograph progression. Remission was to be defined using trial data for use in
      trials but needed to anticipate use in a practice setting. RESULTS: The working
      group started by evaluating the thresholds for core set measures compatible with
      remission and determined that patient-reported outcomes contributed importantly
      to the ability of outcome assessment to distinguish more from less effective
      treatments. The group created a candidate group of remission definitions to test,
      including Boolean versions and widely used indexes. Testing how well these
      candidate definitions predicted later good outcomes, the group found that Disease
      Activity Score 28 thresholds for remission performed worse than Simplified
      Disease Activity Index/Clinical Disease Activity Index or Boolean versions. Also,
      persons with low Disease Activity Score 28 occasionally had high joint counts,
      which were incompatible with remission. The parent committee chose two
      definitions: one Boolean (patient had to have all of the following: tender joint
      count, swollen joint count <= 1, C reactive protein <= 1 mg/dl) and patient
      global assessment <= 1 (on a 0-10 scale) and one Simplified Disease Activity
      Index <= 3.3. CONCLUSION: The American College of Rheumatology/European League
      Against Rheumatism has promulgated two new similar definitions of remission for
      RA trials.

PMID- 22460147
TI  - Remission by imaging in rheumatoid arthritis: should this be the ultimate goal?
AB  - Remission is often selected as the 'treat to target'. There is a plea to include
      imaging. Imaging remission can apply to structural damage and/or inflammation.
      For structural damage, radiographs are mostly used. A definition is needed which
      could be either strict, with no progression occurring, or which takes measurement
      error into account and uses the smallest detectable change. Mostly imaging
      remission refers to inflammation as assessed by ultrasound or MRI. The reason for
      arguing that imaging remission should be included for inflammation is that
      inflammation may still be present in patients who are in clinical remission. The
      level of inflammation depends on the clinical remission definition that is used.
      Bone marrow oedema is the feature that is most predictive of radiographic
      progression. However, before imaging remission can be implemented as a
      recommendation, a definition of remission by imaging needs to be established. A
      choice has to be made about the level of inflammation that can be tolerated and
      how this needs to be assessed (which imaging method, which feature, which joints,
      which cut-off point). Moreover, imaging remission should only be selected as a
      target if it can be proved that it can be treated and that the outcome of the
      patients will be improved by trying to achieve imaging remission in addition to
      clinical remission. This proof is not yet available, and too many unanswered
      questions remain to recommend including imaging remission of inflammation in a
      definition of remission.

PMID- 22460148
TI  - How to define remission in ankylosing spondylitis?

PMID- 22460149
TI  - Roles of LAG3 and EGR2 in regulatory T cells.
AB  - Regulatory T cells (Tregs) participate in the maintenance of tolerance to self
      antigens and suppressive control of excessive immune responses to exogenous
      antigens. A lack or dysfunction of these cells is responsible for the
      pathogenesis and development of many autoimmune diseases. It is well known that
      CD4 Tregs play a major role in controlling immune responses and can be classified
      into two main populations: thymus-derived naturally occurring Tregs (nTregs) and
      induced Tregs (iTregs) generated from CD4(+)CD25(-) precursors in the peripheral
      lymphoid organs. The most extensively studied Tregs are the nTregs, which express
      the interleukin 2 (IL-2) receptor CD25 and the transcription factor Forkhead box
      P3 (Foxp3). On the other hand, iTregs contain multiple heterogeneous subsets,
      including interleukin (IL)-10-producing CD4 type I Tregs (Tr1 cells) and
      transforming growth factor -beta-producing Th3 cells, and so on. However, the
      extent of the contribution of iTregs to immunoregulation in normal animals has
      been difficult to evaluate because of the lack of suitable cell surface markers.
      It has been found recently that IL-10-secreting iTregs can be delineated as
      CD4(+)CD25(-)Foxp3(-) T cells that characteristically express both the lymphocyte
      activation gene-3 (LAG3) and the early growth response gene-2 (EGR2). In this
      review, opinions about the roles of LAG3 and EGR2 in Tregs are presented.

PMID- 22460150
TI  - The interpretation of clinical tests of peripheral vestibular function.
AB  - Recently, new clinical tests of canal and otolith function have been introduced.
      They rest on sound anatomical and physiological evidence; however, the
      interpretation of the results of these tests has only recently been clarified.
      This review summarizes the anatomical and physiological evidence underpinning the
      tests of both canal and otolith function to provide a full picture of the
      interpretation of the tests, which allow the clinician to assess the status of
      the peripheral vestibular function of a patient--all six canals and four
      otoliths. The present review does not document all the minute details associated
      with each test, but provides an overview of the interpretation of properly
      presented tests and shows typical response profiles of patients with various
      types of vestibular loss, based on published anatomical, physiological, and
      clinical evidence.

PMID- 22460151
TI  - A novel approach for addressing Alzheimer's disease: the chemo-optical synergism.

PMID- 22460152
TI  - Interaction between neurotrophin 4 and gonadotrophin in bovine oviducts.
AB  - The expression and localization of neurotrophin 4 (NT4) and its receptor,
      tyrosine kinase B (TRKB), in the bovine oviduct, and their interaction with
      gonadotrophins in bovine oviduct epithelial cells (BOECs), were examined.
      Transcripts for NT4 and TRKB were detected by reverse transcription polymerase
      chain reaction (RT-PCR) in bovine oviducts in the follicular and luteal phases,
      and their proteins were immunolocalized in BOECs. Based on real time PCR, NT4
      mRNA did not differ significantly between the two phases of the cycle, although
      TRKB mRNA expression was higher (P < 0.05) in the luteal phase than that in
      follicular phase. The BOECs were treated with various concentrations of
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in vitro; for
      NT4, mRNA and protein were higher (P < 0.05) than those in the control (based on
      real time PCR and enzyme-linked immunosorbent assay (ELISA) assays). The effects
      of NT4 and the TRKB inhibitor (K252a) on the expression of LH receptor (LHR) and
      FSH receptor (FSHR) in the oviduct epithelial cells were also studied using a
      monolayer culture model. Expression levels of LHR and FSHR mRNA in BOECs treated
      with various concentrations of NT4 were higher (P < 0.05) than those in the
      control. However, these expressions were blocked by treatment with K252alpha. We
      concluded that neurotrophin 4 may have a role in regulating the function of
      bovine oviducts by interacting with gonadotrophins.

PMID- 22460153
TI  - Porcine androgenetic embryos develop to fetal stage in recipient mothers.
AB  - In livestock, parthenogenic embryos are simple to produce, but androgenetic
      embryos have been successfully produced only in sheep and cows. In the present
      study, matured porcine oocytes were enucleated by micromanipulation and then
      fertilized with sperm in vitro, thereby producing porcine androgenetic embryos.
      Porcine androgenetic embryos, which had only sperm genomes, were assessed for
      cleavage and for blastocyst formation 2 and 6 d after IVF, respectively. There
      was no difference in cleavage rate between androgenetic embryos and biparental
      IVF embryos (mean +/- SD androgenetic: 65.5 +/- 5.4%; biparental IVF: 63.2 +/-
      3.6%), but there was a difference in the rate of blastocyst formation
      (androgenetic: 4.5 +/- 0.7%; biparental IVF: 30.2 +/- 2.6%, P < 0.05). The
      average number of cells in Day 6 androgenetic blastocysts (34.3 +/- 18.2) was
      lower (P < 0.05) than that in biparental IVF blastocysts (44.1 +/- 19.5), but did
      not differ from that in parthenogenetic embryos (35.7 +/- 16.7). The androgenetic
      embryos were transferred into recipient mothers to examine the competence of post
      implantation development. Androgenetic fetuses were present on Days 21 and 25,
      but not on Days 28, 31, or 35. Of the six androgenetic fetuses recovered on Day
      21, five had normal, translucent bodies, and two of these five had beating
      hearts. The four fetuses recovered on Day 25 were all non-viable. In conclusion,
      porcine androgenetic embryos initiated embryogenesis and had reached a viable
      fetal stage 21 days after IVF.

PMID- 22460154
TI  - A diet rich in n-3 polyunsaturated fatty acids reduced prostaglandin
      biosynthesis, ovulation rate, and litter size in mice.
AB  - Both n-3 polyunsaturated fatty acids (PUFAs) and conjugated linoleic acid (CLA)
      can alter biosynthesis of prostaglandins E(2) (PGE(2)) and prostaglandin F2alpha
      (PGF(2alpha)), which have critical roles in animal reproduction. The objective
      was to determine the effects of dietary supplementation of fish oil (rich in n
      3PUFAs; N3) or CLA on PGE(2) and PGF(2alpha) production, ovulation rate, and
      litter size, using female transgenerational mice as an experimental model.
      Kunming mice were fed a diet that included 4% soybean oil (rich in n-6PUFAs; N6),
      4% N3, or 4% CLA over three generations (~270 days). Ovarian concentrations of
      PGE(2) and PGF(2alpha), as well as the percentage of arachidonic acid (AA) in
      ovarian phospholipids, cyclooxygenase-2 (COX-2) enzyme activity and protein
      concentrations, were significantly lower in the N3 group than the N6 group. The
      number of ovulated oocytes and presumed zygotes were dramatically reduced,
      whereas the percentage of oocytes trapped in luteinized follicles was increased
      in the N3 group. Furthermore, litter sizes were decreased in the N3 vs. N6 groups
      (P < 0.05) in the second and third generations. In contrast, supplementation with
      CLA did not affect litter size or ovulation rate (P > 0.05). In conclusion,
      transgenerational supplementation with fish oil significantly decreased ovarian
      concentrations of AA and COX-2, concentrations of PGE(2) and PGF(2alpha),
      ovulation rate, and litter size in female mice.

PMID- 22460155
TI  - The impact of molecular imaging in the management of movement disorders: an
      ongoing revolution.

PMID- 22460156
TI  - The molecular basis of dopaminergic brain imaging in Parkinson's disease.
AB  - The central role of dopamine neuronal loss in Parkinson's disease provides a
      clear pathologic framework and rationale for imaging the system both to
      interrogate dynamic pathophysiologic changes as well as to aid in diagnosis and
      clinical management. Recent post mortem studies of Parkinson's brain provide a
      much fuller depiction of the inexorable and progressive topology of
      pathophysiologic changes, including brain alpha-synuclein deposition. This
      informs PET and SPECT evaluations for testing hypotheses regarding the course of
      degeneration in longitudinal studies of Parkinson's disease patients. Recent work
      has underscored the subtlety of change in the dopaminergic neuronal system and
      its neural connections as a function of disease status and treatment. The
      interplay between other neurochemical brain systems and dopamine elucidates
      potential new targets for therapeutic intervention across the stages of the
      disease.

PMID- 22460157
TI  - The role of molecular imaging in the differential diagnosis of parkinsonism.
AB  - This review focuses on the possibilities to use scintigraphic techniques to help
      differentiate neurodegenerative brain diseases associated with parkinsonian
      features. In particular, the findings of dopaminergic imaging, FDG PET imaging,
      and cardiac sympathetic imaging are described. Considerable overlap in individual
      data on striatal postsynaptic D2/3 binding and presynaptic DAT binding/DOPA
      uptake exists between different parkinsonian syndromes, which may hamper its role
      as the sole imaging technique to differentiate PD from other parkinsonian
      syndromes. The results of recent studies suggested, however, that the combination
      of pre- and postsynaptic dopaminergic imaging may gain further insight in the
      pathophysiological mechanisms in patients with parkinsonian features. Also, most
      of the commonly used DAT tracers bind not only to striatal DATs, but to serotonin
      transporters in extrastriatal brain areas as well. Preliminary studies suggest
      that this additional information may be helpful to increase the accuracy to
      differentiate between patients with parkinsonian features. Finally, both brain
      [18F]FDG PET and cardiac sympathetic imaging are very promising tools to
      differentiate different parkinsonian syndromes from each other in routine
      clinical studies.

PMID- 22460158
TI  - Quantitative approaches to dopaminergic brain imaging.
AB  - During the last three decades dopaminergic brain imaging has emerged from a
      dedicated research tool to a widespread and routinely used application. The
      rationale behind this development is on the one hand the well known pathologic
      involvement of the dopaminergic pathway in various neuro-psychiatric diseases,
      and on the other hand the increasing availability of specific radioligands for
      picking up pre- and postsynaptic dopaminergic key functions. In particular the
      commercial availability of SPECT tracers but also the growing number of positron
      emission tomography/computed tomography (PET/CT) imaging devices has contributed
      to the steadily increasing number of diagnostic applications. In an era aiming
      for accurate diagnosis in the early and even preclinical stage of disease,
      refined methodologies are required to detect even subtle changes. In this context
      quantification of dopaminergic functions more and more gains importance. Whereas
      earlier visual assessment was considered sufficient to characterize findings,
      today refined quantitative tools have the potential to deliver information
      beyond. This review briefly addresses the development of quantitative methods for
      dopaminergic brain imaging, from simple manual ratio based applications to
      various automated methodologies, some of them including tools for correction of
      physical parameters such as scatter and septal penetration and partial volume
      effects. Voxel based analysis methods will be covered and also kinetic analyses
      will be briefly touched. The main focus is directed at SPECT rather than PET
      methodologies due to the clinical impact of the first. Finally, some thoughts
      regarding the impact of standardization and harmonization of protocols for
      imaging and processing will be discussed, including the use of normal data bases
      for reference.

PMID- 22460159
TI  - Identification of biomarkers in Lewy-body disorders.
AB  - Dementia with Lewy bodies (DLB) may account for up to 30% of all dementia cases.
      The symptoms of DLB can be difficult to disentangle from other dementia subtypes,
      particularly Alzheimer's disease (AD). AD and DLB pathologies often overlap
      within individuals. Like DLB, Parkinson's disease dementia (PDD) also shares
      common features with DLB. Currently, whether an individual is diagnosed with PDD
      or DLB depends solely on the timing of symptom onset. Early, accurate diagnosis
      is needed for optimal management and treatment. It is hoped that the development
      of existing and new Lewy body disorders biomarkers will facilitate more accurate
      diagnosis. Reduced dopamine transporter levels in DLB as shown with [123I]FP-CIT
      SPECT currently appears to be the most reliable and valid biomarker, although
      other (predominantly imaging-based) methods also appear to have the high
      sensitivity and specificity required for a good biomarker. This includes (in DLB
      compared to AD) reduced cardiac 123I-MIBG uptake, occipital hypometabolism on FDG
      PET and preservation of medial temporal lobe structures on CT/MRI. Perfusion
      SPECT, cerebrospinal fluid protein levels (amyloid, tau and alpha-synuclein),
      electroencephalography, saccadic eye movement tracking and 11C-PiB amyloid
      imaging also hold promise as biomarkers in terms of differentiating DLB, AD, PDD
      and other neurodegenerative disorders, although findings are less consistent.
      Studies utilising a combination approach in which two or more potential
      biomarkers are compared seem to provide very good sensitivity and specificity. In
      general, longitudinal studies, pathological confirmation of diagnosis and the
      combined approach may hold the most promise for the identification of biomarkers.

PMID- 22460160
TI  - Cognitive impairment in degenerative parkinsonisms: role of radionuclide brain
      imaging.
AB  - Cognitive impairment in Parkinson's disease (PD) and atypical parkinsonian
      syndromes is gaining increased clinical significance. The neurochemical and
      neuropathological basis in the various parkinsonian forms and even in an
      individual patient are not fully elucidated yet and could be heterogeneous. Loss
      of dopaminergic, cholinergic and noradrenergic innervation has been suggested to
      be the underlying neurochemical deficits for cognitive impairment and dementia in
      PD, but the onset of cognitive impairment and the progression to dementia may not
      share the same underlying neurochemical basis. Similarly, pathological evidence
      is also heterogeneous, ranging from subcortical pathology, limbic or cortical
      Lewy body type degeneration, and Alzheimer's type pathology that can be found
      even in the same patient with PD dementia (PDD). Typically, the prototype of
      early cognitive deficit in PD is a dysexecutive syndrome, but other cognitive
      domains are more involved when dementia develops, mainly including visuospatial,
      language and memory dysfunction. Functional radionuclide neuroimaging, by means
      of single-photon emission computed tomography and positron emission tomography,
      are contributing to characterize the topographic cortical pattern of cognitive
      impairment, as well as to define the underlying neurochemical deficit. Lastly,
      the advent of amyloid PET may help clarifying the meaning of amyloid load in
      diffuse Lewy body disease and PDD. Knowing the neurochemical and
      pathophysiological substrate of cognitive deficit in patients with PD or other
      degenerative Parkinsonisms may help the clinician in understanding the clinical
      condition of an individual patient in order to plan pharmacological and non
      pharmacological intervention. The introduction of acetylcholinesterase inhibitors
      for therapy of PDD is an example of information integration between clinical
      neuropsychological and pathophysiological-neurochemical aspects obtained also
      with the key contribution of functional neuroimaging.

PMID- 22460161
TI  - New developments of dopaminergic imaging in Parkinson's disease.
AB  - The development of radioligands for the dopaminergic system has provided suitable
      imaging biomarkers for clinical research in Parkinson's disease (PD) and related
      movement disorders. Single photon emission tomography (SPECT) has played an
      important role as main molecular imaging modality because of the availability of
      imaging tools such as dopamine transporter (DAT) radioligands for wide clinical
      use. At present, SPECT imaging of the DAT is the main diagnostic imaging
      procedure for the assessment of patients with parkinsonism. However, in the
      recent years positron emission tomography (PET) has become an important clinical
      diagnostic modality, mainly in oncology, due to the wide availability of PET/CT
      systems with improved imaging performance and to the use of 2-deoxy-2-[18F]fluoro
      D-glucose ([18F]FDG) as main diagnostic agent. In this context, further
      development of 18F-radioligands is of high interest for their potential utility
      in the clinical setting. This review will give a general overview on the
      development of SPECT and PET radioligands for the dopaminergic system and
      describe the potential advantages of developing 18F-labelled radioligands for
      imaging of the dopaminergic system in PD and related movement disorders.

PMID- 22460162
TI  - Barriers to treatment of hepatitis B in an urban Chinatown community.
AB  - GOALS: To evaluate the net effect of a concerted effort to treat hepatitis B
      virus (HBV) in a Chinese immigrant population, including barriers to initiating
      and continuing therapy and antiviral efficacy. BACKGROUND: Oral antiviral agents
      for HBV achieve high rates of viral suppression. However, there is limited
      information about the impact of attempts to treat HBV in high prevalence
      immigrant communities. METHODS: Sixty-nine patients were identified in an urban
      Chinatown Internal Medicine practice who had indications for treatment of HBV. A
      coordinated effort was made to provide antiviral therapy to these patients.
      Barriers to starting treatment and reasons for discontinuation were categorized
      on the basis of a systematic review of medical records. Suppression of HBV DNA to
      undetectable levels was considered a treatment response. RESULTS: Twenty-six
      percent (18/69) of patients did not start medication because of failure to follow
      up or treatment refusal. Oral antiviral therapy was initiated in 74% (51/69) of
      cases and 38 of 39 patients who remained on treatment achieved viral suppression.
      Twelve patients discontinued medication because of social, economic, or other
      reasons. In total, 55% (38/69) of treatment candidates achieved undetectable HBV
      DNA levels on therapy. CONCLUSIONS: Although oral antiviral therapy was highly
      effective in achieving viral suppression in patients who were maintained on
      treatment, only 55% of treatment candidates reached this endpoint. Barriers to
      care kept nearly one half of patients from initiating or continuing therapy. A
      multidisciplinary approach including education and social and financial support
      is needed to maximize the benefit of available HBV treatment in this urban
      immigrant population.

PMID- 22460163
TI  - The effect of socioeconomic status on staging and treatment decisions in
      esophageal cancer.
AB  - BACKGROUND: Optimal treatment choice for patients with esophageal cancer (EC) is
      complex and largely determined by tumor characteristics, comorbidity, and age.
      GOALS: This study describes the role of patient characteristics, among which is
      socioeconomic status (SES), in EC treatment. STUDY: Patients diagnosed with
      primary EC between 1990 and 2008 in the southern part of the Netherlands were
      identified using the Eindhoven Cancer Registry. Multivariable logistic and
      proportional hazard regression analyses were used to identify determinants of
      treatment and survival. RESULTS: We included 1914 patients, and 37% of them
      underwent intentionally curative treatment. Low-SES patients were diagnosed at
      older age (16% vs. 9%, age more than or equal to 80) and with more advanced tumor
      stages (13% vs. 10%, stage T4) than high-SES patients. Age less than 60 compared
      with 70 to 79 years [adjusted odds ratio, 4.51; 95% confidence interval (CI),
      2.98-6.84] and high SES compared with low SES (adjusted odds ratio 1.59; 95% CI,
      1.07-2.37) were independent predictors for curative treatment. Probability of
      death for high-SES patients undergoing palliative treatment was decreased
      compared with low-SES patients (hazard ratio, 0.84; 95% CI, 0.71-0.99).
      CONCLUSIONS: SES is an important factor in treatment choice of EC. As health care
      is equally accessible to the whole population in the Netherlands, this suggests
      that both patient-related and physician-related factors are involved in this
      phenomenon.

PMID- 22460164
TI  - Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma.
AB  - BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive
      malignant tumor of mesothelial origin that shows a limited response to
      cytoreductive surgery along with intraperitoneal chemotherapy. Therefore,
      diagnosing DMPM early is very important. Reactive oxygen species play an
      important role in asbestos toxicity, which is associated with the pathogenesis of
      DMPM growth. Thioredoxin-1 (TRX) is a small redox-active protein that
      demonstrates antioxidative activity associated with tumor growth. Here, we
      investigated the serum levels of TRX in patients with DMPM and compared them with
      those of a population that had been exposed to asbestos but did not have DMPM.
      STUDY: The serum concentrations of TRX were measured in 15 DMPM patients and 34
      individuals with benign asbestos-related diseases. RESULTS: We demonstrated that
      the patients with DMPM had significantly higher serum levels of TRX than the
      population that had been exposed to asbestos but did not have DMPM. CONCLUSIONS:
      Our data suggest that serum TRX concentration is a useful serum marker for DMPM.

PMID- 22460165
TI  - Osteoarthritis: Virtual joint replacement as an outcome measure in OA.

PMID- 22460166
TI  - Delayed enhancement cardiac magnetic resonance imaging can identify the risk for
      ventricular tachycardia in chronic Chagas' heart disease.
AB  - BACKGROUND: Invasive and non-invasive tests have been used to identify the risk
      of ventricular tachycardia (VT) in patients with chronic Chagas' heart disease
      (CCHD). Cardiac magnetic resonance imaging (CMRI) using the delayed enhancement
      (DE) technique can be useful to select patients with global or segmentary
      ventricular dysfunction, with high degree of fibrosis and at higher risk for
      clinical VT. OBJECTIVE: To improve the identification of predictors of VT in
      patients with CCHD. METHOD: This study assessed 41 patients with CCHD [30 (72%)
      males; mean age, 55.1 +/- 11.9 years]. Twenty-six patients had history of VT (VT
      group), and 15 had no VT (NVT group). All patients enrolled had DE and segmentary
      ventricular dysfunction. In each case, the following variables were determined:
      left ventricular volume; percentage of ventricular wall thickness impairment in
      each segment; and DE distribution. RESULTS: No statistical difference regarding
      the DE volume between both groups was observed: VT group = 30.0 +/- 16.2%; NVT
      group = 21.7 +/- 15.7%; p = 0.118. The probability of VT was greater in the
      presence of two or more contiguous transmural fibrosis areas, and that was a
      predictive factor of clinical VT (RR 4.1; p = 0,04). Agreement between observers
      was 100% regarding that criterion (p < 0.001). CONCLUSION: The identification of
      two or more segments of transmural DE by use of CMRI is associated with the
      occurrence of clinical VT in patients with CCHD. Thus, CMRI improved risk
      stratification in the population studied.

PMID- 22460167
TI  - Evaluation of surgical treatment of congenital heart disease in patients aged
      above 16 years.
AB  - BACKGROUND: The increasing number of children with evolving congenital heart
      diseases demands greater preparation of professionals and institutions that
      handle them. OBJECTIVE: To describe the profile of patients aged over 16 years
      with congenital heart disease, who have undergone surgery, and analyze the risk
      factors that predict hospital mortality. METHOD: One thousand five hundred twenty
      patients (mean age 27 +/- 13 years) were operated between January 1986 and
      December 2010. We performed a descriptive analysis of the epidemiological profile
      of the study population and analyzed risk factors for hospital mortality,
      considering the complexity score, the year in which surgery was performed, the
      procedure performed or not performed by the pediatric surgeon and reoperation.
      RESULTS: There was a significant increase in the number of cases from the year
      2000. The average complexity score was 5.4 and the septal defects represented 45%
      of cases. Overall mortality was 7.7% and most procedures (973 or 61.9%) with
      greater complexity were performed by pediatric surgeons. Complexity (OR 1.5),
      reoperation (OR 2.17) and pediatric surgeon (OR 0.28) were independent risk
      factors influencing mortality. Multivariate analysis showed that the year in
      which the surgery was performed (OR 1.03), the complexity (OR 1.44) and the
      pediatric surgeon (OR 0.28) influenced the result. CONCLUSION: There is an
      increasing number of patients aged 16 years which, despite the large number of
      simple cases, the most complex ones were referred to pediatric surgeons, who had
      lower mortality, especially in recent years.

PMID- 22460168
TI  - A dual pH and temperature responsive polymeric fluorescent sensor and its imaging
      application in living cells.
AB  - A polymeric fluorescent sensor PNME, consisting of A4 and N-isopropylacrylamide
      (NIPAM) units, was synthesized. PNME exhibited dual responses to pH and
      temperature, and could be used as an intracellular pH sensor for lysosomes
      imaging. Moreover, it also could sense different temperature change in living
      cells at 25 and 37  degrees C, respectively.

PMID- 22460170
TI  - Plasmids expressing interleukin-10 short hairpin RNA mediate IL-10 knockdown and
      enhance tumor necrosis factor alpha and interferon gamma expressions in response
      to porcine reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) has been suggested to
      exploit interleukin-10 (IL-10) to suppress immune defense of infected pigs. The
      present study constructed plasmids encoding selected short hairpin RNA specific
      to porcine IL-10 mRNA (pIL-10sh) to knockdown IL-10 transcription and
      investigated the suppressive effect of PRRSV-induced IL-10 on various immune
      marker expressions. Naive blood monocytes from eight PRRSV-seronegative pigs were
      transfected with pIL-10sh and pNeg (plasmid vector) prior to PRRSV inoculation
      and subsequent lipopolysaccharide (LPS) stimulation. The mRNA expressions of IL
      10, IL-1beta, IL-12p40, tumor necrosis factor alpha (TNFalpha), interferon gamma
      (IFNgamma), transforming growth factor beta (TGFbeta), CD80, and CD86 were
      evaluated by real-time PCR. The IL-10, TNFalpha, and IFNgamma protein productions
      were determined by ELISA. Compared with non-transfected monocyte control,
      transfection with selected pIL-10sh (pIL-10sh1), but not other pIL-10sh nor pNeg,
      significantly reduced IL-10 expression and significantly enhanced TNFalpha and
      IFNgamma expressions. Slight increases in IL-1beta, IL-12p40, CD80, and CD86
      expressions were also observed. Neither pIL-10sh1 nor pNeg transfection affected
      TGFbeta expression. Our results indicate that PRRSV does exploit IL-10 to
      suppress the expressions of pro-inflammatory cytokines, mainly TNFalpha and
      IFNgamma, and co-stimulatory molecules, CD80 and CD86.

PMID- 22460171
TI  - A systemic vaccine based on Escherichia coli O157:H7 bacterial ghosts (BGs)
      reduces the excretion of E. coli O157:H7 in calves.
AB  - Cattle are the main reservoir of enterohemorrhagic Escherichia coli O157:H7, a
      bacterium that, in humans, causes hemorrhagic colitis and hemolytic uremic
      syndrome (HUS), a life-threatening disease, especially in children and older
      people. Therefore, the development of vaccines preventing colonization of cattle
      by E. coli O157:H7 could be a main tool for an HUS control program. In the
      present study, we evaluated bacterial ghosts (BGs) of E. coli O157:H7 as an
      experimental vaccine against this pathogen. BGs are empty envelopes of Gram
      negative bacteria, which retain the morphological surface make-up of their living
      counterparts and are produced by controlled expression of the cloned protein E,
      which causes loss of all the cytoplasm content. In this work, E. coli O157:H7 BGs
      were used for subcutaneous immunization of calves. The vaccinated animals
      elicited significant levels of BG-specific IgG but not IgA antibodies in serum.
      Low levels of IgA and IgG antibodies against BGs were detected in saliva from
      vaccinated animals. Following oral challenge with E. coli O157:H7, a significant
      reduction in both the duration and total bacterial shedding was observed in
      vaccinated calves compared to the nonimmunized group. We demonstrated that
      systemic vaccination with E. coli O157 BGs provides protection in a bovine
      experimental model. Further research is needed to reach a higher mucosal immune
      response leading to an optimal vaccine.

PMID- 22460172
TI  - In vitro assessment of the feline cell-mediated immune response against feline
      panleukopeniavirus, calicivirus and felid herpesvirus 1 using 5-bromo-2'
      deoxyuridine labeling.
AB  - In this study an in vitro assay was optimized to detect feline proliferating
      lymphocytes as an assessment for the cell-mediated immune response. For this
      purpose, 5-bromo-2'-deoxyuridine (BrdU) labeling was chosen because of its
      sensitivity and the possibility of further characterization of proliferating
      cells. The assay was optimized by selecting the best batch and concentration of
      fetal bovine serum, beta-mercaptoethanol concentration, cell density, BrdU
      incubation time and antigen presenting cell type. Cats were vaccinated with the
      attenuated Nobivac vaccine Tricat and the peripheral blood lymphocyte
      proliferation responses were quantified upon in vitro restimulation with
      inactivated and infectious feline panleukopenia virus (FPV), feline calicivirus
      (FCV) and felid herpesvirus 1 (FeHV-1). Proliferation signals were detected with
      inactivated FeHV-1 in the CD8(+) but not in the CD8(-) T lymphocyte population,
      with inactivated FCV and FPV in both CD8(-) and CD8(+) T lymphocyte populations.
      Restimulation with infectious FCV caused significant proliferation in the CD8(-)
      T lymphocyte population only while infectious FPV and FeHV-1 seemed to suppress
      lymphocyte proliferation in both T cell populations. Additional IFN-gamma
      quantification in the culture supernatant revealed a large correlation between
      the proliferation signals and IFN-gamma production, indicating that BrdU labeling
      is a very reliable technique to assess and characterize feline
      lymphoproliferative responses to viral antigens in vitro.

PMID- 22460173
TI  - Early stage efficacy and toxicology screening for antibiotics and enzyme
      inhibitors.
AB  - The rise in organisms resistant to existing drugs has added urgency to the search
      for new antimicrobial agents. Aspartate beta-semialdehyde dehydrogenase (ASADH)
      catalyzes a critical step in an essential microbial pathway that is absent in
      mammals. Our laboratory is using fragment library screening to identify efficient
      and selective ASADH inhibitors. These preliminary agents are then tested to
      identify compounds with desired antimicrobial properties for further refinement.
      Toward this end, we have established a microplate-based, dual-assay approach
      using a single reagent to evaluate antibiotic activity and mammalian cell
      toxicity during early stage development. The bacterial assay uses nonpathogenic
      bacteria to allow efficacy testing without a dedicated microbial laboratory.
      Toxicity assays are performed with a panel of mammalian cells derived from
      representative susceptible tissues. These assays can be adapted to target other
      microbial systems, such as fungi and biofilms, and additional mammalian cell
      lines can be added as needed. Application of this screening approach to
      antibiotic standards demonstrates the ability of these assays to identify
      bacterial selectivity and potential toxicity issues. Tests with selected agents
      from the ASADH inhibitor fragment library show some compounds with antibiotic
      activity, but as expected, most of these early agents display higher than desired
      mammalian cell toxicity.

PMID- 22460174
TI  - Development of a dimethylarginine dimethylaminohydrolase (DDAH) assay for high
      throughput chemical screening.
AB  - Nitric oxide (NO) is a potent signaling molecule that needs to be tightly
      regulated to maintain metabolic and cardiovascular homeostasis. The nitric oxide
      synthase (NOS)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric
      dimethylarginine (ADMA) pathway is central to this regulation. Specifically, the
      small-molecule ADMA competitively inhibits NOS, thus lowering NO levels. The
      majority of ADMA is physiologically metabolized by DDAH, thus maintaining NO
      levels at a physiological concentration. However, under pathophysiological
      conditions, DDAH activity is impaired, in part as a result of its sensitivity to
      oxidative stress. Therefore, the application of high-throughput chemical
      screening for the discovery of small molecules that could restore or enhance DDAH
      activity might have significant potential in treating metabolic and vascular
      diseases characterized by reduced NO levels, including atherosclerosis,
      hypertension, and insulin resistance. By contrast, excessive generation of NO
      (primarily driven by inducible NOS) could play a role in idiopathic pulmonary
      fibrosis, sepsis, migraine headaches, and some types of cancer. In these
      conditions, small molecules that inhibit DDAH activity might be therapeutically
      useful. Here, we describe optimization and validation of a highly reproducible
      and robust assay successfully used in a high-throughput screen for DDAH
      modulators.

PMID- 22460175
TI  - On the prediction of statistical parameters in high-throughput screening using
      resampling techniques.
AB  - A severe drawback in the high-throughput screening (HTS) process is the
      unintentional (random) presence of false positives and negatives. Their rates
      depend, among others, on the screening process being applied and the target
      class. Although false positives can be sorted out in subsequent process steps,
      their occurrence can lead to increased project cost. More fundamentally, it is
      not possible to rescue false nonhits. In this article, we investigate the
      prediction of the primary hit rate, hit confirmation rate, and false-positive and
      false-negative rates. Results for approximately 2800 compounds are considered
      that are tested as a pilot screen ahead of the primary screening work. This pilot
      screen is done at several concentrations and in replicates. The rates are
      predicted as a function of the proposed hit threshold by having the replicates
      serve as each other's confirmers, and confidence limits to the prediction are
      attached by means of a resampling scheme. A comparison of the rates resulting
      from the resampling with the primary hit rate and the confirmation rates obtained
      during the screening campaign shows how accurate this method is. Hence, the
      "optimal" compound concentration for the screen as well as the optimal hit
      threshold corresponding to low false rates can be determined prior to starting
      the subsequent screening campaign.

PMID- 22460176
TI  - In vitro ADME profiling using high-throughput rapidfire mass spectrometry:
      cytochrome p450 inhibition and metabolic stability assays.
AB  - Early assessment of absorption, distribution, metabolism, and excretion (ADME)
      properties of drug candidates has become an essential component of modern drug
      discovery. ADME characterization is important in identifying compounds early that
      are likely to fail in later clinical development because of suboptimal
      pharmacokinetic properties or undesirable drug-drug interactions. Proper
      utilization of ADME results, meanwhile, can prioritize candidates that are more
      likely to have good pharmacokinetic properties and also minimize potential drug
      drug interactions. By integrating a RapidFire system with an API4000 mass
      spectrometer (RF-MS), we have established a high-throughput capability to profile
      compounds (>100 compounds/wk) in a panel of ADME assays in parallel with
      biochemical and cellular characterizations. Cytochrome P450 inhibition and time
      dependent inhibition assays and microsomal stability assays were developed and
      fully optimized on the system. Compared with the classic liquid chromatography
      mass spectrometry method, the RF-MS system generates consistent data with
      approximately 20-fold increase in throughput. The lack of chromatographic
      separation of compounds, substrates, and metabolites can complicate data
      interpretation, but this occurs in a small number of cases that are readily
      identifiable. Overall, this system has enabled a real-time and quantitative
      measurement of a large number of ADME samples, providing a rapid evaluation of
      clinically important drug-drug interaction potential and drug metabolic
      stability.

PMID- 22460178
TI  - Community-based exercise and wellness program for people diagnosed with Parkinson
      disease:  experiences from a 10-month trial.
AB  - OBJECTIVE: This study considered whether a therapy community could create an
      infrastructure for developing and maintaining a service delivery model grounded
      in a clinic-based physiotherapy model. A longitudinal clinical study was
      conducted to assess the abilities of participants with Parkinson disease in a 10
      month community exercise program. METHODS: Fifteen individuals averaging stage 3
      on the Hoehn and Yahr scale, 6 years since Parkinson disease diagnosis, and 72
      years old, participated. RESULTS: Graphical analysis of ambulation endurance
      demonstrated the strongest improvement over time (11%). Walking speeds, balance,
      and mobility showed a maintenance effect over the 10 months. The total unified
      Parkinson disease rating scale, activities of daily living subscale, and motor
      subscale remained statistically unchanged in the study. Scores on the unified
      Parkinson disease rating scale mentation, behavior, and mood subscale improved by
      38%. None of the scores met or exceeded the minimal detectable change, MDC95 but
      two scores demonstrated more than 10% change. CONCLUSION: This clinical study
      implemented previous short-term research findings into an ongoing community
      wellness program for individuals with Parkinson disease. No community-based
      studies have demonstrated an ability to maintain a group for an extended time
      frame. Group exercise including forward and backward treadmill training, designed
      and monitored by a physical therapist, may improve or maintain functional
      outcomes.

PMID- 22460179
TI  - Assessing a nephrology-focused YouTube channel's potential to educate health care
      providers.
AB  - INTRODUCTION: YouTube has emerged as a potential teaching tool. Studies of the
      teaching potential of YouTube videos have not addressed health care provider
      (HCP) satisfaction; a necessary prerequisite for any teaching tool. We conducted
      a 4-month investigation to determine HCP satisfaction with a nephrology-specific
      YouTube channel. METHODS: The Nephrology On-Demand YouTube channel was analyzed
      from January 1 through April 30, 2011. Sixty-minute nephrology lectures at East
      Carolina University were compressed into 10-minute videos and uploaded to the
      channel. HCPs were asked to answer a 5-point Likert questionnaire regarding the
      accuracy, currency, objectivity and usefulness of the digital format of the
      teaching videos. Means, standard deviations and 2-sided chi-square testing were
      performed to analyze responses. RESULTS: Over 80% of HCPs considered the YouTube
      channel to be accurate, current and objective. A similar percentage considered
      the digital format useful despite the compression of videos and lack of audio.
      CONCLUSIONS: The nephrology-specific YouTube channel has the potential to educate
      HCPs of various training backgrounds. Additional studies are required to
      determine if such specialty-specific channels can improve knowledge acquisition
      and retention.

PMID- 22460180
TI  - Left ventricular hypertrophy and progression of chronic kidney disease.
AB  - Reduced glomerular filtration rate and albuminuria do not account for the total
      risk of developing end-stage renal disease (ESRD), suggesting that other factors
      might be involved in progressive renal function worsening. Among these,
      cardiovascular disease, even subclinical, could play a role. The role of left
      ventricular hypertrophy in this setting is reviewed in light of recent reports
      that showed that it is associated with faster progression of renal disease to
      ESRD requiring dialysis, in both hypertensive and chronic kidney disease
      patients.

PMID- 22460181
TI  - Survival and factors predicting mortality in hemodialysis patients over 75 years
      old.
AB  - BACKGROUND: Patients starting dialysis treatments are increasingly elderly and
      with high morbidity and mortality. Survival and factors influencing mortality are
      discussed. METHODS: We studied 2,601 patients who started hemodialysis in
      Andalucia (Spain) between 2004 and 2007. Of these, 71 patients died in the first
      90 days of hemodialysis treatment and were excluded. Three groups were
      considered: group A, 694 patients aged less than 60 years; group B, 1,203
      patients between 60 and 75 years; and group C, 704 patients aged over 75.
      Survival and factors associated with mortality were studied. RESULTS: Mean
      survival was 46 months in group A, 41.6 in group B and 35 in the very elderly
      group. In univariate analysis using the Cox proportional hazards model, survival
      in the very elderly patients was significantly influenced by low body mass index
      (BMI), venous catheter as initial vascular access, arterial hypertension,
      congestive heart failure (CHF), late referral to nephrologist (<6 months), C
      reactive protein (CRP) >10 mg/dL, serum albumin <3.5 g/dL, Kt/V (Daugirdas) <1.2
      and time of dialysis session <180 minutes. In multivariate analysis, BMI, CHF,
      CRP, low serum albumin, Kt/V and time of dialysis session remained as independent
      predictors of mortality. CONCLUSIONS: Survival of the very elderly patients who
      remained on hemodialysis more than 90 consecutive days was poor (about 3 years).
      Heart failure and malnutrition/inflammation are prognostic factors related to
      mortality in these patients on chronic hemodialysis.

PMID- 22460182
TI  - Associations among chronic kidney disease, high total p-cresylsulfate and major
      adverse cardiac events.
AB  - BACKGROUND: Cardiovascular disease is prevalent among patients with chronic
      kidney disease (CKD). Patients with CKD have elevated levels of p-cresylsulfate
      (PCS), which has been linked with cardiovascular mortality in this population.
      The aim of this study was to evaluate the clinical significance of CKD in
      coronary artery disease (CAD) patients and to investigate whether a significant
      correlation exists between CKD, total PCS and poor clinical outcomes in CAD
      patients. METHODS: We assessed the occurrence of major adverse cardiac events
      (MACEs) among 340 consecutive CAD patients who enrolled in a disease management
      program after the patients were discharged from the hospital. CKD was defined as
      an estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m(2).
      RESULTS: Kaplan-Meier analysis revealed that CKD and high total PCS levels (>1.66
      mg/L) were significantly associated with the occurrence of MACE. A multivariate
      Cox hazard regression model revealed that the predictive independent risk factor
      for the occurrence of MACE was high total PCS level (relative risk = 1.387). We
      divided the patients with or without CKD and high or low total PCS levels into 4
      groups according to their eGFR and total PCS levels, respectively. The hazard
      ratio for MACE in the group with both CKD and high total PCS level was 1.721,
      relative to the group without CKD that had low total PCS level (p=0.005).
      CONCLUSIONS: A high serum level of total PCS may be a predictor of elevated risk
      of MACE in CAD patients with low eGFR.

PMID- 22460184
TI  - Peritoneal phosphate removal varies by peritoneal dialysis regimen: an
      underestimated parameter of phosphate control.
AB  - BACKGROUND: The optimization of phosphate (P) removal by peritoneal dialysis (PD)
      is often underestimated. Our objective was to investigate peritoneal P clearance
      and its relationship with standard adequacy targets, hyperphosphatemia and
      automated PD (APD) parameters. METHODS: Dialysis dose, P clearances (24-hour
      urine and effluent samples), estimated percentage of diffusive P removal and
      peritoneal transport rate (PET) were evaluated in 77 adult prevalent PD patients.
      RESULTS: Total P removal strongly correlated with residual renal function
      parameters, dissociated from peritoneal Kt/V urea (r=-0.36; p=0.02) and
      creatinine clearance (r=-0.32; p<0.0001). A correlation of P clearance with net
      ultrafiltration was not found. Among the variables studied, only renal and
      peritoneal P clearances were significantly lower in hyperphosphatemic patients.
      In APD, peritoneal phosphate clearance was positively correlated with 4-hour
      dialysate to plasma creatinine ratio (r=0.46; p=0.039). Slow transporters had
      higher peritoneal P clearances under continuous ambulatory PD (CAPD) regimens.
      Hyperphosphatemia was significantly associated with a lower number of APD cycles
      and shorter nightly therapy time, with insufficient dwell time individualization.
      CONCLUSIONS: P peritoneal clearance is a modifiable parameter of P control in PD
      regimens and an additional adequacy target. Prescription skills are recommended
      in APD patients, particularly in anurics, to take into account peritoneal
      transport rate.

PMID- 22460183
TI  - IgA nephropathy with severe chronic renal failure: a randomized controlled trial
      of corticosteroids and azathioprine.
AB  - BACKGROUND: Therapeutic nihilism is common in IgA nephropathy (IgAN) and renal
      insufficiency. METHODS: In a randomized controlled trial comparing steroids alone
      or combined with azathioprine in 253 IgAN patients, we used a separate
      randomization list for patients with creatinine >2.0 mg/dL. Twenty patients
      (group 1) were randomized to 3 intravenous pulses of methylprednisolone 1 g at
      months 1, 3 and 5, and oral prednisone 0.5 mg/kg every other day plus
      azathioprine 1.5 mg/kg/day for 6 months, followed by oral prednisone 0.2 mg/kg
      every other day plus azathioprine 50 mg/day for a further 6 months; 26 patients
      (group 2) received steroids alone. The primary outcome was renal survival (50%
      increase in plasma creatinine from baseline); secondary outcomes were proteinuria
      over time and adverse events. RESULTS: Six-year renal survival was not different
      between the 2 groups (50% vs. 57%; log-rank p=0.34). Median proteinuria decreased
      during follow-up in the whole population (from 2.45 g/day [interquartile range
      (IQR) 1.50-3.78] to 1.09 g/day [IQR 0.56- 2.46]; p<0.001), with no between-group
      difference. Multivariate predictors associated with renal survival were sex of
      patient, proteinuria during follow-up, number of antihypertensive drugs,
      angiotensin-converting enzyme inhibitors and treatment including azathioprine.
      Six patients in group 1 (30%) and 4 in group 2 (15%) did not complete the
      therapy, because of side effects (p=0.406). CONCLUSIONS: Six-year renal survival
      was similar in the 2 groups. At Cox analysis the addition of azathioprine may be
      slightly more effective than corticosteroids alone in patients with chronic renal
      insufficiency, although with an increase of side effects.

PMID- 22460186
TI  - Intracystic papillary carcinoma of the breast: report of two cases.
AB  - Intracystic papillary carcinoma (IPC) of the breast has traditionally been
      considered to be a variant of ductal carcinoma in-situ (DCIS). It is an uncommon
      tumor accounting for less than 3% of all breast cancers and predominantly affects
      elderly women. IPC is extremely rare in men and only few cases have been reported
      in the literature. The tumor has excellent prognosis regardless of whether it is
      in-situ or invasive. Hence an accurate diagnosis plays a crucial role in the
      management of patients with IPC. We report two cases of IPC, one in a 68-year-old
      woman and the other one in a 70-year-old man. The diagnosis was suspected on fine
      needle aspiration cytology (FNAC) and was confirmed by histopathology.

PMID- 22460187
TI  - Mechanical properties and characteristics of developmental copolymers
      incorporating catechin or chlorhexidine.
AB  - OBJECTIVES: This study evaluated catechin and chlorhexidine release from
      copolymers based on bis-GMA diluted with TEGDMA (R1), propoxylated bis-GMA
      CH(3)bis-GMA (R2) or fluorinated bis-GMA-CF(3)bis-GMA (R3). Mechanical
      properties, degree of conversion, water sorption and solubility were also tested.
      METHODS: Experimental comonomers (R1, R2, R3) were prepared combining bis-GMA
      with the diluents (70/30 mol%). Each comonomer had either catechin or
      chlorhexidine incorporated in the following ratios: 0, 0.2, 1.0, 2.0 wt%. The
      degree of conversion (%DC) of resins was evaluated by FT-IR spectrophotometry
      (n=3). Flexural strength and elastic modulus were tested on a universal testing
      machine at a crosshead speed of 0.5mm/min (n=6). Resin disks (7 mm in diameter *
      2 mm high) were immersed in deionized water and mass changes recorded daily.
      Spectral measurements were made to follow any changes in optical densities of
      deionized water in order to examine catechin and chlorhexidine release rates
      (n=6). After a 28-day period, water sorption and solubility were calculated using
      appropriate equations (n=6). Data within the tests were evaluated by one- and
      three-way ANOVA and Tukey-Kramer's test (alpha=0.05). RESULTS: Except for R1 with
      2.0% drug none of the groups had changes in degree of conversion and water
      sorption. Solubility increased with increased drug ratios. Changes in flexural
      strength and elastic modulus were shown to be variable and material-dependent.
      All resins presented a ~24 h burst of drug release. Release rates were drug-ratio
      dependent and significantly higher for chlorhexidine than for catechin.
      SIGNIFICANCE: Monomer type, %DC, drug ratio and type lead to different
      interactions between resins and chlorhexidine/catechin drug particles. It should
      be possible to develop different resins based on clinical needs.

PMID- 22460188
TI  - [Prevalence of hypercalciuria in postmenopausal women with osteoporosis].
AB  - OBJECTIVE: To determine the prevalence of hypercalciuria (HC) in postmenopausal
      women with osteoporosis and its relationship with clinical data and bone mineral
      metabolism. SUBJECTS AND METHODS: Calciuria was measured in 24-hour urine samples
      of 127 women. BMD was measured in the lumbar spine and femur by dual-energy X-ray
      absorptiometry (DXA). RESULTS: Mean age (+/-SD) was 64 (+/-8) years. According to
      urinary calcium excretion, patients were divided into normo- and hypercalciuric
      (HC). Of the 127 patients, 19 (15%) were classified as HC. The only difference
      between the groups was the age of onset of menopause (46 +/- 6 vs. 50 +/- 3 years
      HC, p < 0.0005). No association was found between calciuria and age, BMI, BMD,
      calcium, phosphorus, PTH, and alkaline phosphatase. CONCLUSION: HC is frequent in
      postmenopausal women with osteoporosis, and calciuria measurement should be
      included in the investigation of these patients.

PMID- 22460189
TI  - [Physical activity and healthcare cost of type 2 diabetic patients seen at basic
      units of healthcare].
AB  - OBJECTIVES: To observe differences in healthcare costs according to the level of
      physical activity in type 2 diabetes mellitus. SUBJECTS AND METHODS: A total of
      121 type 2 diabetic patients were interviewed in two basic units of healthcare in
      Bauru, Brazil. Physical activity level was assessed by a questionnaire carried
      out during an interview. Costs of exams, medications and doctor and nurse visits
      were assessed for the previous year using invoices obtained from basic units of
      healthcare. RESULTS: Sedentary type 2 diabetic patients presented higher costs
      for doctor visits (63%; p = 0.017) and medication to treat diseases other than
      diabetes (p = 0.001) than active patients. CONCLUSIONS: Sedentary type 2 diabetic
      patients presented higher healthcare costs related to doctor visits and medicine
      purchase.

PMID- 22460190
TI  - Influence of visceral and subcutaneous fat in bone mineral density of obese
      adolescents.
AB  - OBJECTIVE: To verify the influence of visceral and subcutaneous fat, as well
      adipokines in bone mineral density (BMD) in obese adolescents. SUBJECTS AND
      METHODS: The study involved 125 postpubertal obese adolescents (45 boys and 80
      girls). Anthropometric measurements, body composition, visceral and subcutaneous
      fat, and BMD were determined. Leptin, adiponectin, and insulin levels also
      analyzed. RESULTS: Data demonstrated a negative relationship between BMD with
      insulin resistance, visceral fat and leptin concentration; and bone mineral
      content with visceral/subcutaneous ratio. Positive association between BMD and
      subcutaneous fat was observed. CONCLUSIONS: Visceral fat and insulin resistance,
      as well as visceral/subcutaneous ratio and leptin concentration, were negative
      predictors of BMD in boys and girls, respectively. However, subcutaneous fat had
      a protective influence in BMD only in boys.

PMID- 22460191
TI  - [Preliminary comparison between phalangeal quantitative ultrassonography and bone
      densitometry for bone mass evaluation in adolescents].
AB  - OBJECTIVE: To evaluate the association between quantitative ultrasonography at
      hand phalanges (QUS) and dual energy X-ray absorptiometry (DXA), and between
      these methods with food intake and history of bone fractures. SUBJECTS AND
      METHODS: After two years of follow up of 270 schoolchildren, 10 of them, who
      showed bone mass below - 2 SD in QUS, were included in the present study.
      Laboratory results and DXA data were analyzed. RESULTS: Bone mass evaluated by
      DXA at L1-L4 ranged from -2.8 to -1.1 SDS, and whole body bone mass, from -2.9 to
      -1.2 SDS. Three children had history of non-pathological bone fractures. Dietary
      assessment showed low intake of calcium in 10 cases, of phosphorus in 6, and of
      vitamin D in 8 cases. There were no differences among the cases of bone mass
      below-2 SD in any of the three used methods. There was no association between
      history of bone fractures and food intake, and between these evaluations and bone
      mass. CONCLUSION: In this small group of schoolchildren there was an association
      between the methods QUS and DXA. However, there was no association between bone
      mass and the history of bone fractures, or calcium, phosphorus and vitamin D
      intake.

PMID- 22460192
TI  - [Spirulina, exercise and serum glucose control in diabetic rats].
AB  - OBJECTIVE: The objective of this study was to analyze the effect of Spirulina
      and/or exercise training in the control of serum glucose homeostasis in diabetic
      rats. MATERIALS AND METHODS: Young Wistar rats were induced to diabetes by
      intravenous alloxan administration and separated into four groups: diabetic
      control (DC), diabetic Spirulina (DS), diabetic exercise (DE) and diabetic
      exercise Spirulina (DES). RESULTS: There were no differences between groups with
      respect to: body weight, food intake, glucose tolerance, insulin tolerance and
      blood lactate concentrations during a swimming effort test. DS group showed lower
      insulin concentrations when compared with DC (pancreas) and DE and DES (serum).
      CONCLUSION: The protocols of exercise and supplementation with Spirulina used in
      the present study were not able to improve serum glucose homeostasis in diabetic
      rats.

PMID- 22460194
TI  - [Trends in mortality of diabetes mellitus patients in Brazilian capitals, 1980
      2007].
AB  - OBJECTIVE: To analyze mortality patterns of patients with diabetes in Brazilian
      capitals from 1980 to 2007. MATERIALS AND METHODS: Age-standardized quadrennial
      and annual mortality rates were calculated with the world population as
      reference. Linear regression models were estimated to analyze mortality trends in
      each capital. RESULTS: In the first quadrennial period, the highest rate was
      42.89/100,000 in Aracaju; and in the last quadrennial period, 54.38/100,000 in
      Sao Luis. Although mortality rates showed statistically significant incremental
      trends in most capitals, there were regional differences. Belo Horizonte was the
      only capital to show a declining trend. CONCLUSIONS: Part of the observed
      increment could be attributed to improvements in access to diagnosis and death
      certification, but regional differences in the prevalence of diabetes risk and
      protective factors might also be implicated. The absence of a time series of
      incident cases makes it difficult to determine if these results reflect current
      trends in the incidence of diabetes in Brazil.

PMID- 22460193
TI  - Evaluation of quality of life in severely obese patients after bariatric surgery
      carried out in the public healthcare system.
AB  - OBJECTIVES: To assess QoL of obese patients in the Brazilian public healthcare
      system, before and after bariatric surgery, and to determine the appropriateness
      of the Moorehead-Ardelt Questionnaire II (M-A-QoLQII) compared with the Short
      Form Health Survey (SF-36). SUBJECTS AND METHODS: Forty-one severe obese patients
      in a waiting-list, and 84 patients who underwent bariatric surgery were included.
      Correlations were tested and reliability determined by the Cronbach's
      coefficient. RESULTS: BMI differed between the pre- and post-surgery groups (52.3
      +/- 8.3 kg/m(2) vs. 32.5 +/- 6.4 kg/m(2), p < 0.001). The latter showed better
      scores in the SF-36 domains than in the pre-surgery. SF-36 and M-A-QoLQII
      categories were correlated (r = 0.53, 0.49 and 0.47, for vitality, mental health,
      and general health domains, p < 0.001). In the logistic regression, age, previous
      BMI, and loss of excess weight were associated with functional capacity.
      CONCLUSIONS: The outcomes of bariatric surgery obtained in a Brazilian public
      healthcare center were successful. M-A-QoLII represents a useful tool to assess
      surgery outcomes, including QoL.

PMID- 22460195
TI  - Relationship of short tandem repeats flanking leptin-melanocortin pathway genes
      with anthropometric profile and leptinemia in Brazilian individuals.
AB  - OBJECTIVE: To investigate the relationship of short tandem repeats (STR) near
      genes involved in the leptin-melanocortin pathway with body mass index (BMI) and
      leptinemia. SUBJECTS AND METHODS: Anthropometric variables and leptinemia were
      measured in 100 obese and 110 nonobese individuals. D1S200, D2S1788, DS11912, and
      D18S858 loci were analyzed by PCR and high-resolution electrophoresis. RESULTS:
      Overall STR allele frequencies were similar between the obese and non-obese group
      (p > 0.05). Individual alleles D1S200 (17), D11S912 (43), D18S858 (11/12) were
      associated with obesity (p < 0.05). Individuals carrying these alleles showed
      higher BMI than non-carriers (p < 0.05). Moreover, a relationship between D18S858
      11/12 alleles and increased waist circumference was found (p = 0.040). On the
      other hand, leptinemia was not influenced by the studied STRs (p > 0.05).
      CONCLUSIONS: D1S200, D11S912, and D18S858 loci are associated with increased BMI
      and risk for obesity in this sample.

PMID- 22460196
TI  - Autoimmune polyendocrine syndrome type 1: case report and review of literature.
AB  - Autoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive
      disorder characterized by autoimmune multiorgan attack. The disease is caused by
      mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE
      protein, which is essential for selftolerance. Clinical manifestations are widely
      variable. Although the classic triad is composed by mucocutaneous candidiasis,
      hypoparathyroidism and adrenal failure, many other components may develop.
      Treatment is based on supplementation of the various deficiencies, and patients
      require regular follow-up throughout their lifespan. This article describes the
      case of a patient with the disease, and reviews literature data on the
      epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of
      the syndrome.

PMID- 22460197
TI  - Is there a role for inherited TRbeta mutation in human carcinogenesis?
      [corrected].
AB  - Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited
      disorder characterized by end-organ reduced sensitivity to thyroid hormone. This
      syndrome is caused by mutations of the thyroid hormone receptor (TR) beta gene,
      and its clinical presentation is quite variable. Goiter is reported to be the
      most common finding. A close association of TRbeta mutations with human cancers
      has become apparent, but the role of TRbeta mutants in the carcinogenesis is
      still undefined. Moreover, higher TSH levels, described in RTH syndrome, are
      correlated with increased risk of thyroid malignancy, whereas TSH receptor
      stimulation is likely to be involved in tumor progression. We report here an
      illustrative case of a 29 year-old patient with RTH caused by a mutation in exon
      9 (A317T) of TRbeta gene, who presented multicentric papillary thyroid cancer. We
      review the literature on this uncommon feature, and discuss the potential role of
      this mutation on human tumorigenesis, as well as the challenges in patient follow
      up.

PMID- 22460198
TI  - [Interferon-alpha: a endocrine disruptor?].

PMID- 22460201
TI  - A bifunctional catalyst for carbon dioxide fixation: cooperative double
      activation of epoxides for the synthesis of cyclic carbonates.
AB  - We have developed a very active bifunctional porphyrin catalyst showing a high
      turnover number (TON = 103,000) for the synthesis of cyclic carbonates from CO(2)
      and epoxides under solvent-free conditions.

PMID- 22460200
TI  - Modulation of somatosensory evoked potentials during force generation and
      relaxation.
AB  - This study investigated the modulation of somatosensory evoked potentials (SEPs)
      during precisely controlled force generation and force relaxation in a visuomotor
      tracking task. Subjects were instructed to track a target line with a line that
      represented their own force generated by grip movement with the right hand as
      accurately as possible during concurrent electrical stimulation. The target force
      line moved up continuously from 0 to 20 % of maximal voluntary contraction (MVC)
      (the force generation phase: FG phase) and moved down from 20 to 0 % of MVC (the
      force relaxation phase: FR phase) in 7 s at a constant velocity. We separately
      obtained SEPs following electrical stimulation of the median nerve at the wrist
      in each phase. During the visuomotor tracking task, compared with the stationary
      condition, the N30 at Fz and P27 at C3' showed a significant reduction in
      amplitude in the FG and FR phases. In addition, the N30 and P27 were
      significantly smaller in amplitude in the FG than FR phase. Although the average
      amount of force exertion was the same in the FG and FR phases, the modulation of
      SEP amplitude was larger in the FG phase. These results indicated that
      sensorimotor integration in the somatosensory area was dependent on the context
      of movement exertion.

PMID- 22460202
TI  - Systemic arterial response and ventriculo-arterial interaction during normal
      pregnancy.
AB  - BACKGROUND: During normal pregnancy (NP), cardiac output (CO) increases, and
      blood pressure and systemic vascular resistance are reduced. We wanted to
      evaluate systemic arterial properties and interaction between the left ventricle
      (LV) and systemic arteries during NP. The role of systemic arteries and their
      interaction with LV-function in this hemodynamic response, lack description.
      METHODS: We used noninvasive methods to study 65 healthy women (32 +/- 5 years)
      with NP repeatedly at gestational weeks 14-16, 22-24, 36, and 6 months postpartum
      (PP). Aortic root pressure and flow were obtained by calibrated right subclavian
      artery pulse traces and aortic annular Doppler flow recordings. Arterial
      properties were described by estimates of total arterial compliance (C), proximal
      aortic stiffness (characteristic impedance (Z(0))), arterial elastance (Ea), and
      peripheral arterial resistance (R). Ventriculo-arterial coupling (VAC) was
      characterized by the ratio between arterial (E(a)I) and LV (E(LV)I) elastance
      index. RESULTS: During NP, CO increased by 20% due to increased heart rate and
      stroke volume. Mean arterial pressure was reduced by 10% (P < 0.001) as compared
      to 6 months PP. R was reduced by 5% (P < 0.01), Z(0) trended lower and C higher.
      E(a)I decreased (P < 0.01) and E(LV)I was reduced to a higher extent resulting in
      29% increase of E(a)I/E(LV)I during NP (P < 0.01). CONCLUSIONS: During NP there
      is an increase in CO, and decrease in blood pressure and R whereas central aortic
      properties are less altered. The increased VAC index (E(a)I/E(LV)I) during NP
      indicates a decrease in LV-function not fully compensated for by vascular
      adaptation.

PMID- 22460203
TI  - Salvage radiotherapy in patients with persistently detectable PSA or PSA rising
      from an undetectable range after radical prostatectomy gives comparable results.
AB  - PURPOSE: Salvage radiotherapy (SRT) is applied routinely in patients with a
      biochemical relapse after radical prostatectomy (RP). Although the detection
      threshold for relapse after RP has steadily been lowered, only about 30% of the
      SRT patients achieve a durable response. We have previously shown the association
      between a PSA decrease below detectable levels after SRT and biochemical
      progression-free survival (BPFS). After recalculating our data according to a
      more recent definition of biochemical failure after SRT, we now show the
      significance of the post-RP PSA nadir. MATERIALS AND METHODS: Among 159 prostate
      cancer patients without hormonal treatment after RP, SRT was given to 72 patients
      with persistently detectable PSA after RP and to 87 whose PSA increased out of an
      undetectable range. The median pre-SRT PSA was 0.29 ng/ml for the former group
      and 0.34 ng/ml for the latter group. A radiation dose of 66.6 Gy was applied to
      the prostate bed. RESULTS: The overall median follow-up time was 41.7 months. The
      probability for BPFS after this period was 52.8% in 72 patients with persistently
      detectable PSA after RP and 65.4% in 87 patients who had a post-RP PSA nadir
      below detection limit. Univariate and multivariate analyses showed no significant
      difference in BPFS of both patient groups (p > 0.05). CONCLUSION: Our findings
      suggest that SRT is a viable treatment option for patients with persistently
      detectable PSA, giving similar results as in patients whose PSA increases out of
      an undetectable range after RP.

PMID- 22460204
TI  - Hereditary thrombophilic risk factors for recurrent pregnancy loss.
AB  - This review summarizes current knowledge about the role of hereditary
      hypercoagulation factors predisposing to thrombophilia-associated recurrent fetal
      loss. Thrombophilias are a major cause of adverse pregnancy outcome, playing a
      role in the etiology of up to 40% of cases worldwide. Hereditary thrombophilic
      predispositions to recurrent pregnancy wastage include genetic lesions in blood
      coagulation factors II and V as well as natural anticoagulants antithrombin,
      protein C, and protein S. Furthermore, methylenetetrahydrofolate reductase gene
      variants conferring higher thrombophilia risk in combination with these mutations
      and the newly described annexin A5 gene M2 promoter allele are associated with
      repeated fetal loss. The review gives a concise description of the molecular
      defects arising from the genetic changes, of the role these factors play in the
      timing and definition of fetal loss, and risk estimates from available studies
      and meta-analysis. This knowledge is instrumental for a more precise assessment
      of individual risks for repeated fetal loss and should guide therapeutic
      strategies, where relevant. Since the average childbearing age increases in
      Western societies, the importance of a timely diagnosis of fetal loss
      predisposition is increasing.

PMID- 22460205
TI  - Genetic variants at the APOE, lipoprotein lipase (LpL), cholesteryl ester
      transfer protein (CETP), and endothelial nitric oxide (eNOS) genes and coronary
      artery disease (CAD): CETP Taq1 B2B2 associates with lower risk of CAD in Asian
      Indians.
AB  - Coronary artery disease (CAD) arises due to a complex interplay between the
      environment and genetic factors. Alterations in many of the biomarkers such as
      lipids and lipoprotein levels are characteristic of CAD. The phenotypes
      themselves have genetic determinants, and many single-nucleotide polymorphisms
      (SNPs) have been identified which influence them. The current study aims to
      evaluate the effect of six common polymorphisms at four loci, lipoprotein lipase
      (D9N, N291S, S447X), apolipoprotein E (APOE), cholesteryl ester transfer protein
      (C277T), and endothelial nitric oxide synthase (E298D), on lipid and lipoprotein
      levels and its association with CAD. Genotyping for the SNPs was done in 240
      Indians of which 90 had proven CAD. The other 150 were clinically free from CAD
      and acted as controls. Relation of genetic variants, clinical history, and
      biochemical parameters with CAD were analyzed by multiple regression analysis.
      The frequency of the B2 allele in the CETP gene was significantly lower in cases
      than in controls (0.40 vs 0.49, P = 0.042). Significant association of CETP Taq1B
      SNP was seen with total cholesterol and low density lipoprotein cholesterol.
      Multivariate analysis accounting for clinical and metabolic predictors of CAD
      showed smoking to be a significant risk factor (odds ratio (OR) 4.347, 95%
      confidence interval (CI) 1.888-10.012, P = 0.001) and the CETP B2 variant
      imparting atheroprotection (OR 0.312, 95% CI 0.116-0.841, P = 0.021) possibly
      through a favorable lipid profile. None of the other SNPs were associated with
      the risk of CAD.

PMID- 22460206
TI  - Updating and refining a study brochure for a cancer registry-based study of BRCA
      mutations among young African American breast cancer patients: lessons learned.
AB  - The aim of the present study was to update, refine, and evaluate a study brochure
      to promote participation in a population-based study of BRCA mutations among AA
      women with a personal history of early-onset breast cancer. A multi-step approach
      was used to develop this brochure and included: (1) feedback from community
      members (through a Community Advisory Panel (CAP)) to develop and refine the
      study brochure, (2) pilot testing of materials with the target audience, and (3)
      review of pilot testing results with the CAP. Based on the feedback received at
      each step, the study brochure was refined. In phase 1, the major changes included
      emphasizing the concept of leaving a legacy and family, using the terms Black and
      women of color, and use of patient vignettes and photos. In phase 2, attraction
      and cultural acceptability were identified as two areas for improvement in the
      study brochure. These results demonstrate that involvement of community members
      and target study population in the development of a study-specific brochure can
      provide invaluable feedback to optimize recruitment strategies. This approach can
      be readily adapted to develop study recruitment materials for individuals from a
      variety of cultural and ethnic backgrounds.

PMID- 22460207
TI  - Developing and evaluating a culturally appropriate genetic service for
      consanguineous South Asian families.
AB  - Blackburn with Darwen Primary Care Trust (PCT) provides services to a substantial
      Asian population in which the practice of consanguineous marriage is common and
      there is a high incidence of autosomal recessive disorders. The aim was to
      provide and evaluate a genetic service accessible to consanguineous families from
      the South Asian community who had a child affected by an autosomal recessive
      disorder. Information on genetic risk was provided along with the offer of
      genetic testing for members of the extended family to identify gene carriers and
      facilitate informed reproductive choices. An Urdu-speaking health visitor was
      employed to establish a community-based, hospital-linked genetic service in
      conjunction with local paediatric and regional genetic services offered to
      parents who had an affected child and 71 of their relatives. The service was
      evaluated using a specifically designed questionnaire. There was a high uptake of
      the service (95% of index parents and 92% of relatives to whom it was offered)
      and a high uptake of carrier testing (94% of relatives to whom it was offered).
      Eight requests for prenatal diagnosis were made during the course of the service
      development. Many individuals stated they would consider genetic risk when making
      future marriage and reproductive plans. Input from a health care worker from the
      same ethnic background who provided information in their own language was highly
      valued. Family orientated genetic services for ethnic groups practicing
      consanguinity can be acceptable and effective when provided in a culturally
      appropriate manner.

PMID- 22460208
TI  - Breast and ovarian cancer risk evaluation in families with a disease-causing
      mutation in BRCA1/2.
AB  - Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian
      cancer, and their identification allows genetic testing of at-risk relatives.
      However, estimates of these risks illustrate controversies, depending on the
      published series. The penetrance, the earlier onset of the disease and the effect
      of mutations on the risk of developing breast and ovarian cancer were evaluated
      in 344 females belonging to 34 families from the Basque Country in Spain, in
      which BRCA1 or BRCA2 mutations were transmitted. Kaplan-Meier survival curves
      were used to derive cumulative probability curves for breast and ovarian cancer
      by mutation status, birth cohort and mutation position, and significance of the
      differences was assessed using the log-rank test. The estimated probability for
      breast cancer by age 70 is about 64% in BRCA1 and 69% in BRCA2, whereas the
      probability of developing ovarian cancer is about 37% and 25% for BRCA1 and
      BRCA2, respectively. There is a marginally significant higher risk of developing
      ovarian cancer in BRCA1 families than in BRCA2 families. The effect of birth
      cohort on breast cancer cumulative incidence presents an increased risk for
      females born after 1966 and a decreased risk for those born before 1940. There is
      no association between mutation position and breast cancer; however, ovarian
      cancer is associated to BRCA1, presenting exon 11 as an ovarian cluster. These
      results are important for the breast and ovarian cancer diagnosis and prevention
      in at-risk families.

PMID- 22460209
TI  - Emerging health threats: why do they need a new journal?

PMID- 22460211
TI  - Influenza and respiratory syncytial virus infections in British Hajj pilgrims.
AB  - Viral respiratory infections including influenza and respiratory syncytial virus
      (RSV) have been reported during the Hajj among international pilgrims. To help
      establish the burden of these infections at the Hajj, we set up a study to
      confirm these diagnoses in symptomatic British pilgrims who attended the 2005
      Hajj. UK pilgrims with symptoms of upper respiratory tract infection (URTI) were
      invited to participate; after taking medical history, nasal swabs were collected
      for point-of-care testing (PoCT) of influenza and for subsequent PCR analysis for
      influenza and RSV. Of the 205 patients recruited, 37 (18%) were positive for
      either influenza or RSV. Influenza A (H3) accounted for 54% (20/37) of the virus
      positive samples, followed by RSV 24% (9/37), influenza B 19% (7/37), and
      influenza A (H1) 3% (1/37). Of the influenza-positive cases, 29% (8/28) had
      recently had a flu immunisation. Influenza was more common in those who gave a
      history of contact with a pilgrim with a respiratory illness than those who did
      not (17 versus 9%). The overall rate of RSV was 4% (9/202). This study confirms
      that influenza and RSV cause acute respiratory infections in British Hajj
      pilgrims. Continuing surveillance and a programme of interventions to contain the
      spread of infection are needed at the Hajj, particularly when the world is
      preparing for an influenza pandemic.

PMID- 22460210
TI  - Gulf War syndrome: an emerging threat or a piece of history?
AB  - 'Gulf War syndrome' is a phrase coined after the 1991 Gulf War to group together
      disparate, unexplained health symptoms in Gulf veterans. This paper examines the
      many hypotheses that have been put forward about the origins of the concept and
      gives an overview of the studies that have attempted to explain the lasting
      health effects associated with Gulf service. Our review finds that although in
      the UK there has not yet been evidence of a new Gulf War syndrome as a result of
      the current conflicts in Iraq and Afghanistan, there is a rise in post-conflict
      psychiatric disorders now being reported in the USA. We postulate that after
      conflicts military personnel will always face some form of post-conflict syndrome
      and the nature of the threats experienced is likely to dictate the form the
      syndrome might take. We also postulate that media reporting is likely to have
      influenced and to continue unhelpfully to influence the health of service
      personnel.

PMID- 22460212
TI  - Biodefense countermeasures: the impact of Title IV of the US Pandemic and All
      Hazards Preparedness Act.
AB  - The 2006 US Pandemic and All-Hazards Preparedness Act gave the Department of
      Health and Human Services (HHS) new authority to fund the development and
      procurement of medical countermeasures against chemical, biological,
      radiological, and nuclear (CBRN) threats. The legislation builds on the authority
      the HHS gained in 2004 under Project BioShield, which established a fund to
      procure medical countermeasures. This article reviews the new HHS authorities and
      the improvements on BioShield, and it describes some of the challenges HHS will
      face in exercising the new authorities to fund the development and procurement of
      medical countermeasures against CBRN threats.

PMID- 22460213
TI  - Development of a national burn network: providing a co-ordinated response to a
      burn mass casualty disaster within the Australian health system.
AB  - With the threat of terrorist activity ever present since the incidents in Bali
      and Jakarta, the Australian health system must be prepared to manage another mass
      burn casualty disaster. The Australian and New Zealand Burns Association (ANZBA)
      highlighted the lack of a national burn disaster response before the 2000
      Olympics. With the limited number of burn beds available and the protracted
      length of stay after such injuries, any state or territory could be overwhelmed
      with relatively few patient admissions. In 2002, the Australian Health Minister's
      Conference called for a solution. The objective of this paper is to provide an
      overview of the process and development of the Australian National Burn Network,
      which underpins the National Burn Disaster Response (AUSBURNPLAN).

PMID- 22460214
TI  - Knowledge-base black holes: the next (small) big thing?

PMID- 22460215
TI  - Syphilis in China: the great comeback.
AB  - China is currently witnessing a major resurgence of syphilis from the elimination
      of the disease in the 1960s to 5.3 per 100,000 people incidence in 2000-2005. The
      reasons for the elimination and subsequent resurgence of syphilis in China lie at
      the heart of much public health debate, highlighting both the relationship
      between politics and public health, and the role of government in controlling
      disease. Were the Draconian measures to control syphilis during the early Mao
      years a price worth paying for the effective control? Is the recent resurgence of
      syphilis an inevitable consequence of economic development and greater freedom
      for the individual, which will ultimately lead to better health for the majority
      of the population? Could tougher control measures such as those of the early Mao
      years be re-introduced in the current social and economic climate in China? In
      this review, we briefly chart the history of the syphilis epidemic in China, its
      elimination in the 1960s, and its gradual resurgence in the past two decades. We
      explore the reasons for this resurgence, and we conclude with a discussion on the
      options for control.

PMID- 22460216
TI  - Chronic health effects of sulphur mustard exposure with special reference to
      Iranian veterans.
AB  - The widespread use of sulphur mustard (SM) as an incapacitating chemical warfare
      agent in the past century has proved its long-lasting toxic effects. It may also
      be used as a chemical terrorist agent. Therefore, all health professionals should
      have sufficient knowledge and be prepared for any such chemical attack. SM exerts
      direct toxic effects on the eyes, skin, and respiratory tissue, with subsequent
      systemic action on the nervous, immunological, haematological, digestive, and
      reproductive systems. SM is an alkylating agent that affects DNA synthesis, and,
      thus, delayed complications have been seen since the First World War. Cases of
      malignancies in the target organs, particularly in haematopoietic, respiratory,
      and digestive systems, have been reported. Important delayed respiratory
      complications include chronic bronchitis, bronchiectasis, frequent
      bronchopneumonia, and pulmonary fibrosis, all of which tend to deteriorate with
      time. Severe dry skin, delayed keratitis, and reduction of natural killer cells
      with subsequent increased risk of infections and malignancies are also among the
      most distressing long-term consequences of SM intoxication. However, despite a
      lot of research over the past decades on Iranian veterans, there are still major
      gaps in the SM literature. Immunological and neurological dysfunction, as well as
      the relationship between SM exposure and mutagenicity, carcinogenicity, and
      teratogenicity are important fields that require further studies, particularly on
      Iranian veterans with chronic health effects of SM poisoning. There is also a
      paucity of information on the medical management of acute and delayed toxic
      effects of SM poisoning-a subject that greatly challenges health care
      specialists.

PMID- 22460218
TI  - Meeting the needs of people in emergencies: a review of UK experiences and
      capability.
AB  - This article summarises the key findings of two research studies conducted for
      the UK Government in 2006-2007. The first was a literature review of evidence
      about provisions and interventions to meet the needs of people affected by
      'emergencies' as defined within the Civil Contingencies Act (2004). Drawing on
      both historical and contemporary research and practice, the literature review
      presented an assessment of people's psychosocial needs after events such as
      natural disasters, terrorism, and other major incidents. Although some reference
      was made about the needs of and consequences on disaster workers responding to
      these events, the main emphasis was on those directly affected as bereaved people
      and/or injured survivors. The review offered best practice guidelines based on
      the most effective methods of humanitarian assistance in the immediate, short
      term, and long-term aftermath of major emergencies. The second report was a
      follow-up study conducted in 2007. This was a piece of primary research focusing
      on the UK's current capability in humanitarian assistance in terms of the extent
      of planning, training, exercising, and experience relating to meeting people's
      needs in emergencies. A variety of methods were used to gather quantitative and
      qualitative evidence of the nature and status of such activity across the UK,
      including questionnaires, focus groups, and a review of literature and
      documentary evidence. The report included a number of good practice case studies
      and made recommendations for the development of best practice in humanitarian
      assistance within the UK.

PMID- 22460219
TI  - Responsiveness of human monocytes to the commensal bacterium Staphylococcus
      epidermidis develops late in gestation.
AB  - INTRODUCTION: Staphylococcus epidermidis (SE) rarely causes infection in term
      infants but is a leading cause of late-onset sepsis in preterm infants. We
      hypothesized that the innate immune responses to SE in preterm infants are
      impaired in a gestational age (GA)-dependent manner. METHODS: Cord and peripheral
      blood mononuclear cells (MNCs) were stimulated with SE bacteria, and a range of
      innate immune responses were assessed, including phagocytosis, intracellular
      killing, Toll-like receptor (TLR) pathway transcriptional activation, cytokine
      production, TLR2 and TLR4 expression, and cell signaling. RESULTS: Phagocytosis
      and intracellular killing of SE bacteria were similar in neonatal and adult
      monocytes. Cytokine gene expression and protein synthesis increased in a GA
      dependent manner, which was confirmed at the single-cell level. These GA-related
      effects were not associated with differences in expression of TLR2 or TLR4, nor
      with downstream activation of nuclear factor-kappaB or mitogen-activated protein
      kinase pathways. DISCUSSION: The expression of TLRs, phagocytic capacity, and
      intracellular killing by monocytes develops early in fetal development, whereas
      the ability to mount a bacteria-induced cytokine response requires further
      maturation. The functional immaturity of monocyte activation pathways in the
      preterm infant may underpin their particular susceptibility to sepsis with
      commensal bacteria.

PMID- 22460217
TI  - Hepatitis E: a complex and global disease.
AB  - Thirty years after its discovery, the hepatitis E virus (HEV) continues to
      represent a major public health problem in developing countries. In developed
      countries, it has emerged as a significant cause of non-travel-associated acute
      hepatitis. HEV infects a wide range of mammalian species and a key reservoir
      worldwide appears to be swine. Genomic sequence similarity between some human HEV
      genotypes and swine HEV strains has been identified and we know that humans can
      acquire HEV infection from animals. Although for the most part the clinical
      course of HEV infection is asymptomatic or mild, significant risk of serious
      disease exists in pregnant women and those with chronic liver disease. In
      addition, there are data on the threat of chronic infections in immunocompromised
      patients. Beyond management of exposure by public health measures, recent data
      support that active immunisation can prevent hepatitis E, highlighting the need
      for vaccination programmes. Here we review the current knowledge on HEV, its
      epidemiology, and the management and prevention of human disease.

PMID- 22460220
TI  - Prevalence of organic colonic lesions in patients meeting Rome III criteria for
      diagnosis of IBS: a prospective multi-center study utilizing colonoscopy.
AB  - BACKGROUND: It remains unknown whether the Rome III criteria can exclude organic
      colonic lesions prior to the diagnosis of irritable bowel syndrome (IBS). We
      evaluated the colonoscopy results of patients meeting the Rome III criteria for
      the diagnosis of IBS to determine the presence of organic colonic lesions.
      METHODS: This study was prospectively conducted at 17 centers in Japan. We
      enrolled 4528 patients who underwent diagnostic colonoscopy examinations. The
      diagnosis of IBS was evaluated by questionnaire results according to the Rome III
      criteria. RESULTS: We evaluated 4178 patients (350 were excluded because of
      incomplete data or previous colonic surgery), of whom 203 met the Rome III
      criteria (mean age 57.9 years; range 14-87 years) prior to the diagnostic
      colonoscopy examination. We identified organic colonic diseases in 21 of these
      203 patients (10.3 %) , and these disease were also identified in 338 (8.5 %) of
      3975 patients who did not fulfill the Rome III criteria. There were no
      differences in regard to the prevalence of organic colonic diseases between
      patients who did and did not fulfill the Rome III criteria. CONCLUSIONS: The
      prevalence of organic colonic diseases in patients who met the Rome III criteria
      was at an acceptably low level, indicating that the Rome III criteria are
      adequately specific for the diagnosis of IBS without performing a colonoscopy
      examination.

PMID- 22460223
TI  - Estrogenic plant foods of red colobus monkeys and mountain gorillas in Uganda.
AB  - Phytoestrogens, or naturally occurring estrogen-mimicking compounds, are found in
      many human plant foods, such as soybeans (Glycine max) and other legumes. Because
      the consumption of phytoestrogens may result in both health benefits of
      protecting against estrogen-dependent cancers and reproductive costs of
      disrupting the developing endocrine system, considerable biomedical research has
      been focused on the physiological and behavioral effects of these compounds.
      Despite this interest, little is known about the occurrence of phytoestrogens in
      the diets of wild primates, nor their likely evolutionary importance. We
      investigated the prevalence of estrogenic plant foods in the diets of two
      folivorous primate species, the red colobus monkey (Procolobus rufomitratus) of
      Kibale National Park and mountain gorilla (Gorilla beringei) of Bwindi
      Impenetrable National Park, both in Uganda. To examine plant foods for estrogenic
      activity, we screened 44 plant items (species and part) comprising 78.4% of the
      diet of red colobus monkeys and 53 plant items comprising 85.2% of the diet of
      mountain gorillas using transient transfection assays. At least 10.6% of the red
      colobus diet and 8.8% of the gorilla diet had estrogenic activity. This was
      mainly the result of the red colobus eating three estrogenic staple foods and the
      gorillas eating one estrogenic staple food. All estrogenic plants exhibited
      estrogen receptor (ER) subtype selectivity, as their phytoestrogens activated
      ERbeta, but not ERalpha. These results demonstrate that estrogenic plant foods
      are routinely consumed by two folivorous primate species. Phytoestrogens in the
      wild plant foods of these two species and many other wild primates may have
      important implications for understanding primate reproductive ecology.

PMID- 22460221
TI  - Anemia and thrombocytosis induced by ribavirin monotherapy in patients with
      chronic hepatitis C.
AB  - BACKGROUND: An inosine triphosphatase (ITPA) single-nucleotide polymorphism (SNP)
      is associated with anemia induced by pegylated interferon and ribavirin (RBV)
      combination therapy in patients with chronic hepatitis C (CHC). However, there
      are very few reports on the hematological effects of RBV monotherapy. Here,
      hematological changes were monitored in patients with CHC who received RBV
      monotherapy, and the mechanism of these changes was investigated. METHODS:
      Patients with CHC (n = 30) received RBV monotherapy for 4 weeks. The RBV dose was
      determined on the basis of body weight. Complete blood count, and serum
      erythropoietin (EPO) and thrombopoietin (TPO) levels were assessed. The
      associations between these parameters and the ITPA SNP (rs1127354) were analyzed.
      RESULTS: Over the 4 weeks, the median hemoglobin level of all patients decreased
      significantly, from 13.6 (10.5-16.6) to 11.7 (9.4-14.9) g/dl (P < 0.001), and the
      platelet counts increased, from 14.0 * 10(4) (8.9-37.4 * 10(4)) to 15.8 * 10(4)
      (10.2-40.6 * 10(4)) /mm(3) (P = 0.003). At week 4, hemoglobin levels differed
      between patients with the ITPA CC genotype and those with the AA or AC genotypes
      [11.1 (9.4-13.5) vs. 12.9 (12.5-14.9) g/dl, P = 0.001]. The platelet change ratio
      (i.e., platelet count at week 4/platelet count at baseline) in the patients with
      developing anemia was correlated with the increase in the serum EPO level over 4
      weeks (r = 0.88, P = 0.002), but not with the increase in the serum TPO level
      over 4 weeks. CONCLUSIONS: RBV monotherapy induced anemia and affected
      thrombocytosis in patients with CHC. Elevated endogenous EPO may stimulate
      platelet production.

PMID- 22460225
TI  - Condom use with serious and casual heterosexual partners: findings from a
      community venue-based survey of young adults.
AB  - Given the racial/ethnic disparities that characterize STI trends and recent
      increases in heterosexually transmitted HIV infection in the US, an understanding
      of factors underlying condom use among young adults in minority communities is
      vitally important. To this end, this paper presents findings from a community
      venue-based survey examining the influence of motivations, heuristics, and
      relationship factors on condom behaviors with serious and casual heterosexual
      partners in a sample of urban African American and Puerto Rican males and females
      ages 18-25 (n = 380). Condom use rates at time of last sex were considerably
      higher with casual partners (n = 87) than with serious (n = 313) partners, 77.9%
      vs. 38.7%. While dual pregnancy/STI prevention was the most frequently cited
      reason for use at last sex with casual partners, pregnancy prevention was the
      most frequently cited reason for use with serious partners. Bivariate conditional
      logistic regression analyses found two factors to be associated with condom use
      at last sex with casual partners: use at first sex with the partner and belief
      that neighborhood peers worried some/a lot about HIV. In contrast, such factors
      as condom heuristics (e.g., nonuse symbolizes trust), contraceptive status, and
      markers of emotional intimacy were associated with condom use with serious
      partners in both bivariate and multivariable analyses.

PMID- 22460224
TI  - Pitt-Hopkins syndrome-associated mutations in TCF4 lead to variable impairment of
      the transcription factor function ranging from hypomorphic to dominant-negative
      effects.
AB  - Transcription factor TCF4 (alias ITF2, SEF2 or E2-2) is a broadly expressed basic
      helix-loop-helix (bHLH) protein that functions as a homo- or heterodimer.
      Missense, nonsense, frame-shift and splice-site mutations as well as
      translocations and large deletions encompassing TCF4 gene cause Pitt-Hopkins
      syndrome (PTHS), a rare developmental disorder characterized by severe motor and
      mental retardation, typical facial features and breathing anomalies. Irrespective
      of the mutation, TCF4 haploinsufficiency has been proposed as an underlying
      mechanism for PTHS. We have recently demonstrated that human TCF4 gene is
      transcribed using numerous 5' exons. Here, we re-evaluated the impact of all the
      published PTHS-associated mutations, taking into account the diversity of TCF4
      isoforms, and assessed how the reading frame elongating and missense mutations
      affect TCF4 functions. Our analysis revealed that not all deletions and
      truncating mutations in TCF4 result in complete loss-of-function and the impact
      of reading frame elongating and missense mutations ranges from subtle
      deficiencies to dominant-negative effects. We show that (i) missense mutations in
      TCF4 bHLH domain and the reading frame elongating mutation damage DNA-binding and
      transactivation ability in a manner dependent on dimer context (homodimer versus
      heterodimer with ASCL1 or NEUROD2); (ii) the elongating mutation and the missense
      mutation at the dimer interface of the HLH domain destabilize the protein; and
      (iii) missense mutations outside of the bHLH domain cause no major functional
      deficiencies. We conclude that different PTHS-associated mutations impair the
      functions of TCF4 by diverse mechanisms and to a varying extent, possibly
      contributing to the phenotypic variability of PTHS patients.

PMID- 22460226
TI  - HIV prevention interventions for adolescents and young adults: what about the
      needs of gay and bisexual males?
AB  - While rates of HIV infection among gay/bisexual male adolescents have been
      increasing in the U.S., there has not been a commensurate increase in the
      development of HIV prevention interventions targeted specifically for this
      population. This editorial review examines primary HIV prevention interventions
      published in peer-reviewed journals between 1991 and 2010 in order to explore the
      differential focus on heterosexual versus gay/bisexual male adolescents/young
      adults. Of the 92 articles reviewed, only 5 (5.44 %) included interventions that
      addressed gay/bisexual sexual orientation or same-gender sexual activity. HIV
      prevention interventions developed for adolescents/young adults in the U.S. are
      not targeting those at highest risk of infection. Recommendations for addressing
      this gap are discussed.

PMID- 22460227
TI  - Rates of testing for HIV in the presence of serodiscordant UAI among HIV-negative
      gay men in committed relationships.
AB  - We examined testing rates for HIV-negative men (N = 752) from a sample of gay
      male couples. Approximately half (52 %) tested in the past year. Among men who
      had engaged in sexual risk behavior in the past 3 months, 27 % tested within that
      period and 65 % within the past year. For men in concordant relationships these
      rates were 25 and 60 %, for men in serodiscordant relationships they were 34 and
      72 %. MSM in primary relationships are testing at lower rates than the general
      MSM population, even after potential exposure to HIV. Testing and prevention
      messages for MSM should factor in relationship status.

PMID- 22460228
TI  - Supporting study product use and accuracy in self-report in the iPrEx study: next
      step counseling and neutral assessment.
AB  - The recent successes of biomedical HIV prevention approaches have sparked
      considerable debate over the scalability, feasibility, and acceptability of pre
      exposure prophylaxis (PrEP) as a widespread prevention strategy for men who have
      sex with men and trans-gender. Anticipated difficulties with PrEP adherence and
      concerns about resources required to best support it have tempered enthusiasm of
      PrEP demonstration projects and roll-out. While no evidence-based approach for
      supporting PrEP use is presently available, a number of approaches have been
      developed in the context of double-blind, randomized, placebo-controlled trials
      of PrEP that can provide guidance in moving forward with real world support of
      open label PrEP use. We present the development, implementation and evaluation of
      feasibility and acceptability of next-step counseling (NSC) and neutral
      assessment (NA), the adherence support and promotion of accurate reporting
      approaches used in the late phases of the iPrEx study. Evaluation of the approach
      from the perspective of implementers of over 15,000 NSC sessions in seven
      different countries with almost 2,000 iPrEx participants provided support for
      NSC, its brevity (averaging ~14 min per follow-up session) and overall
      acceptability and feasibility. NA also was generally well supported, with a
      majority of study staff believing this approach was feasible and acceptable;
      however, lower acceptability for certain aspects of NA was noted amongst staff
      reporting NA was different from their previous interview approach. Quantitative
      and qualitative data gathered from implementers were used to make modifications
      for supporting PrEP use in the open-label extension of iPrEx.

PMID- 22460229
TI  - Airway management for intubation in newborns with Pierre Robin sequence.
AB  - OBJECTIVES/HYPOTHESIS: To review airway management in Pierre Robin sequence (PRS)
      newborns undergoing general anesthesia and to determine if endotracheal
      intubation is safe in this population. STUDY DESIGN: Case series and
      retrospective chart review at a tertiary children's hospital. METHODS: PRS
      newborns who underwent endotracheal intubation or other airway intervention
      before 3 months of age between January 2000 and July 2011 were identified from a
      pediatric otolaryngology practice database. Indications for airway intervention,
      anesthetic management, method of intubation, and comorbid conditions were
      collected. RESULTS: Thirty-three PRS newborns were identified. Twenty had
      isolated PRS, and 13 had PRS related to a coexisting syndrome. Thirteen of 35
      (37%) endotracheal intubations performed in PRS newborns prior to mandibular
      distraction osteogenesis were accomplished with direct laryngoscopy. The
      remaining 22 of 35 (63%) who failed intubation with direct laryngoscopy were
      intubated over a flexible fiberoptic bronchoscope. No significant difference was
      observed between the isolated and syndromic PRS newborns with regard to technique
      utilized for intubation. No patient required rescue laryngeal mask airway or
      emergent tracheotomy, and no case resulted in death. CONCLUSIONS: This series
      demonstrates that endotracheal intubation is safe and effective in PRS newborns.
      In patients who failed intubation with direct laryngoscopy, intubation over a
      flexible fiberoptic bronchoscope provided a reliable alternative method. Although
      airway management in PRS newborns poses a significant challenge, experienced
      otolaryngologists and anesthesiologists can successfully manage these difficult
      airway cases.

PMID- 22460231
TI  - Soft-templating synthesis of mesoporous magnetic CuFe2O4 thin films with ordered
      3D honeycomb structure and partially inverted nanocrystalline spinel domains.
AB  - Combining sol-gel chemistry with polymer templating strategies enables production
      of CuFe(2)O(4) thin films with both an ordered cubic network of 17 nm diameter
      pores and tunable spinel domain sizes. These nanocrystalline materials contain
      only minor structural defects with lambda = 0.85 +/- 0.02 and exhibit multiple
      functionalities, including superparamagnetic behavior (T(B)~ 310 K) and redox-
      and photoactivity.

PMID- 22460230
TI  - The relationship of surface roughness and cell response of chemical surface
      modification of titanium.
AB  - Implant surface topography influences osteoblastic proliferation, differentiation
      and extracellular matrix protein expressions. Previous researches proved that
      chemical surface modification of titanium implants could be used to improve Bone
      to-implant contact. In this study, the surface topography, chemistry and
      biocompatibility of polished titanium surfaces treated with mixed solution of
      three acids containing HCl, HF and H(3)PO(4) with different etched conditions for
      example concentration, time and addition of calcium chloride were studied.
      Osteoblast cells (MG-63) were cultured on different groups of titanium surfaces.
      In order to investigate titanium surfaces, SEM, AFM and EDS analyses were carried
      out. The results showed that surfaces treated with HCl-HF-H(3)PO(4) had higher
      roughness, lower cytotoxicity level and better biocompatibility than controls.
      Moreover, addition of calcium chloride into mixed solution of three acids
      containing HCl, HF and H(3)PO(4) is an important, predominant and new technique
      for obtaining biofunction in metals for biomedical use including dentistry.

PMID- 22460232
TI  - The relationship between high-density lipoprotein cholesterol and coronary
      collateral circulation in patients with coronary artery disease.
AB  - INTRODUCTION: High-density lipoprotein cholesterol (HDL-C) promotes cholesterol
      efflux from macrophage foam cells in atheroma plaques. In addition, HDL-C has
      anti-inflammatory and endothelium-protective properties. Despite that the only
      prerequisite for collateral development is shown to be the degree of coronary
      artery stenosis, there are significant differences even among patients with a
      similar degree of coronary artery disease. OBJECTIVE: We designed this study to
      investigate a possible association between HDL-C and coronary collateral
      circulation (CCC). MATERIALS AND METHODS: All study participants had at least one
      occluded major coronary artery. Demographic, clinical, and laboratory data were
      obtained from patients' medical records. To classify CCC, we used Rentrop
      classification. The patients were then classified as having poor CCC (Rentrop
      grades 0-1) or good CCC (Rentrop grades 2-3). We performed t test and the chi
      test in comparing groups and multivariate logistics regression analysis to
      determine the predictors of CCC. The study population consisted of 151 patients
      (mean age, 63.7 +/- 9 years; 76.2% male). RESULTS: Forty-nine patients had poor
      CCC and 102 patients had good CCC. The proportion of previous myocardial
      infarctions, serum triglycerides, and low HDL-C levels were more frequent in the
      poor CCC group (P = 0.026, P = 0.015, and P < 0.001, respectively). Multivariate
      logistic regression analysis revealed that low HDL-C is a predictor of CCC (B =
      1.456; P < 0.001; odds ratio, 4.3; 95% confidence interval, 1.964-9.369).
      CONCLUSION: We found that low HDL-C frequency was more frequent in the poor CCC
      group than the good CCC group, and HDL-C was a predictor of CCC.

PMID- 22460233
TI  - Antiplatelet therapy for secondary prevention of acute coronary syndrome,
      transient ischemic attack, and noncardioembolic stroke in an era of cost
      containment.
AB  - Physicians are aware of the profound impact of oral antiplatelet therapy for
      secondary prevention of acute coronary syndrome (ACS), transient ischemic attack,
      and noncardioembolic stroke. Numerous clinical studies have compared the benefits
      of aspirin (ASA) alone with those of combination therapy with extended-release
      dipyridamole or with those of clopidogrel, with or without ASA, for secondary
      stroke prevention; and of ASA monotherapy compared with ASA plus clopidogrel
      combination therapy for secondary prevention in various ACS populations. More
      recently, ASA plus prasugrel has been compared with ASA plus clopidogrel in a
      high-risk ACS population. However, given the different treatment modalities and
      methods used in the various trials, it is difficult to make generalizations as to
      which therapy is most effective with the lowest risk of bleeding. Further
      complicating physician's decision making are cost considerations, particularly
      with the newer oral antiplatelet agents, which are considerably more expensive
      than ASA. This review provides a brief overview of the clinical data on each of
      the currently marketed oral antiplatelet agents and the available data on cost
      effectiveness for the secondary prevention of ACS, transient ischemic attack, and
      noncardioembolic stroke.

PMID- 22460234
TI  - Placental protein 13 as an early predictor in Egyptian patients with
      preeclampsia, correlation to risk, and association with outcome.
AB  - INTRODUCTION: Placental protein 13 (PP13) is a protein expressed only in the
      placenta. It is involved in gluing the placenta to the uterus and remodeling the
      maternal arteries to expand them. Women who subsequently develop preterm
      preeclampsia have low first trimester maternal serum. AIM OF WORK: The aim of
      this work was to assess the value of PP13 as an early marker for screening of
      preeclampsia and to correlate it with the PP13 messenger RNA (mRNA). PATIENTS AND
      METHODS: As a part of the Antenatal Screening Project, 100 women in the first
      trimester of pregnancy were selected and subdivided into 2 groups: 50 women who
      developed preeclampsia in their third trimester (patient group) and 50 women who
      completed normal uncomplicated pregnancy until full term (control group).
      Placental protein 13 level was measured using the commercially available enzyme
      linked immunosorbent assay kit and PP13 mRNA was tested using reverse
      transcription polymerase chain reaction. RESULTS: The maternal serum PP13 level
      in the preeclamptic group was (157.9 +/- 45.5 pg/mL), which is significantly
      lower than that of the control group (225.3 +/- 67.3 pg/mL), with highly
      statistically significant difference (P < 0.0001). The frequency of maternal PP13
      mRNA expression was lower in the preeclamptic group (28%) compared to that in the
      control group (76%), with highly statistically significant difference (P <
      0.0001). CONCLUSION: Combined serum PP13 level assay and PP13 mRNA expression are
      reliable markers for early detection of preeclampsia, and we recommend doing it
      as a routine investigation during the first trimester.

PMID- 22460235
TI  - Simplifying the growth of hybrid single-crystals by using nanoparticle
      precursors: the case of AgI.
AB  - We report the synthesis of a series of AAg(m)I(n) single-crystals within 24 h, at
      room temperature, utilizing AgI nanoparticles (NPs) as the precursor. The AgI NPs
      impart high reactivity under mild conditions and favor the growth kinetics. 0D,
      1D and 2D iodoargentate crystals can be obtained. This work represents the first
      application of NPs in the field of organo-metal-halide crystals and will inspire
      the design of other AM(m)X(n) crystals.

PMID- 22460236
TI  - Academic motivation, self-concept, engagement, and performance in high school:
      key processes from a longitudinal perspective.
AB  - The study tested three theoretically/conceptually hypothesized longitudinal
      models of academic processes leading to academic performance. Based on a
      longitudinal sample of 1866 high-school students across two consecutive years of
      high school (Time 1 and Time 2), the model with the most superior heuristic value
      demonstrated: (a) academic motivation and self-concept positively predicted
      attitudes toward school; (b) attitudes toward school positively predicted class
      participation and homework completion and negatively predicted absenteeism; and
      (c) class participation and homework completion positively predicted test
      performance whilst absenteeism negatively predicted test performance. Taken
      together, these findings provide support for the relevance of the self-system
      model and, particularly, the importance of examining the dynamic relationships
      amongst engagement factors of the model. The study highlights implications for
      educational and psychological theory, measurement, and intervention.

PMID- 22460237
TI  - School connectedness, peer attachment, and self-esteem as predictors of
      adolescent depression.
AB  - Recent literature suggests that school connectedness (SC) may be a key
      determinant of adolescent mental health. Specifically, SC has been found to have
      a negative relationship with adolescent depression. In the current, cross
      sectional study, we examine whether the relationship between SC and symptoms of
      low mood is dampened or moderated by self-esteem (SE) and peer attachment style.
      Participants were 5022 adolescents (aged 11-16) who completed a battery of
      questionnaires in school, including measures of low mood, SC, SE, and peer
      attachment style. The relationship between SC and low mood was reduced by the
      inclusion of SE and peer attachment style. Peer attachment style was the largest
      predictor of low mood. The relationship between SC and low mood was not moderated
      by SE or peer attachment style. Interventions for adolescent depression may be
      most effective by focussing on increasing SE and fostering secure attachments,
      rather than solely focussing on increasing SC.

PMID- 22460238
TI  - The relation between bullying, victimization, and adolescents' level of
      hopelessness.
AB  - In this study, 419 Turkish middle school students (203 girls, 216 boys) were
      surveyed on their exposure to and engagement in bullying, and their level of
      hopelessness. Our findings suggest that girls were victims of indirect (e.g.
      gossiping) bullying more than boys. Boys reported being victims of physical (e.g.
      damaging property) and verbal (e.g. teasing) bullying more than girls. While the
      level of hopelessness among victims of physical and verbal bullying was higher
      than non-victims, no difference was found between the victims of indirect
      bullying and non-victims. Students who never talked to their teachers and parents
      about bullying reported higher levels of hopelessness than others. The
      implications of the study for intervention and prevention programs are discussed.

PMID- 22460240
TI  - Antibiotic use in children and the use of medicines by parents.
AB  - OBJECTIVE: Antibiotic drugs are frequently used for viral infections in children.
      It is probable that health beliefs and parental concern have great influence on
      the use of drugs in children. This study, performed in The Netherlands,
      investigates whether the use of antibiotics in children is associated with the
      use of medicines by parents. PATIENTS AND METHODS: In this observational cohort
      study, the authors selected 6731 children from the prescription database IADB.nl
      who did not receive antibiotics until their fifth birthday and 1479 children who
      received at least one antibiotic prescription every year. The authors then
      selected parents for each group of children (5790 mothers and 4250 fathers for
      the children who did not receive antibiotics and 1234 mothers and 1032 fathers
      for the children who regularly received antibiotics). The authors compared the
      use of antibiotics and other medicines between the two groups of parents.
      RESULTS: Parents of children who received antibiotics recurrently were found to
      use more antibiotics themselves compared with parents of children who did not
      receive antibiotics. Moreover, this group also showed a higher percentage of
      chronic medication use: (11.3 vs 6.2% (mothers) and 13.1% vs 9.5% (fathers)).
      Mothers more often use antacids, non-steroidal anti-inflammatory drugs (NSAIDs),
      analgesics, anxiolytics, hypnotics, antidepressants, drugs for treatment of
      asthma and antihistamines. Fathers use more antacids, cardiovascular drugs,
      NSAIDs and asthma drugs. CONCLUSIONS: The parents of children who receive
      antibiotic drugs regularly use more medicines compared with the parents of
      children who use no antibiotic drugs. Parents' medicine use may influence that of
      children and is a factor physicians and pharmacists should take into account.

PMID- 22460239
TI  - A pharmacokinetic, pharmacodynamic, and electrocardiographic study of liposomal
      mifamurtide (L-MTP-PE) in healthy adult volunteers.
AB  - PURPOSE: This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD),
      safety/tolerability, and cardiac safety of liposomal muramyl tripeptide
      phosphatidyl-ethanolamine [mifamurtide (L-MTP-PE)] in healthy adults. METHODS: L
      MTP-PE 4 mg was administered intravenously over 30 min. Study participants were
      monitored from 24 h preinfusion until 72 h postinfusion. Blood samples were drawn
      over 0-72 h postdose to determine serum MTP-PE, interleukin (IL)-6, tumor
      necrosis factor (TNF)-alpha, and C-reactive protein (CRP) concentrations.
      Electrocardiograpic (ECG) data were collected via continuous Holter monitoring
      beginning 24 h predose through 24 h postdose. Changes from time-matched
      pretreatment baseline QTc and associated two-sided 90 % confidence intervals were
      calculated. RESULTS: Twenty-one participants received L-MTP-PE. Total serum MTP
      PE declined rapidly with a terminal half-life of 2.05 +/- 0.40 h. PK variability
      was low, with <30 % coefficient of variation in systemic exposure. Serum
      concentrations of IL-6, TNF-alpha, and CRP increased following L-MTP-PE infusion.
      Maximum observed increases in IL-6 and TNF-alpha occurred at 4 and 2 h,
      respectively, returning toward baseline by 8 h postdose. L-MTP-PE was generally
      well tolerated, with no adverse events greater than grade 3. Headache, chills,
      tachycardia, nausea, and pyrexia were the most frequent adverse events. L-MTP-PE
      infusion resulted in an increased heart rate without readily apparent QTc
      prolongation. CONCLUSIONS: MTP-PE PK following L-MTP-PE administration were
      characterized by a short serum half-life and low variability. Increases in IL-6,
      TNF-alpha, and CRP and the safety profile were consistent with the
      immunomodulatory mechanism of action. No clinically significant effect of L-MTP
      PE on cardiovascular repolarization was observed based on analysis of ECG QTc
      intervals.

PMID- 22460241
TI  - Adverse cardiovascular outcomes associated with concurrent use of clopidogrel or
      ticlopidine and proton-pump inhibitors in patients undergoing percutaneous
      coronary intervention.
AB  - Recent clinical studies reported the drug interaction between proton-pump
      inhibitors (PPI) and clopidogrel, which remains controversial. The aim of this
      study was to determine whether the concurrent use of PPI with clopidogrel or
      ticlopidine is associated with increased risk for adverse cardiovascular outcomes
      in patients with coronary artery disease (CAD) undergoing percutaneous coronary
      intervention (PCI). In this retrospective cohort study, we assessed the
      cardiovascular outcomes associated with the concurrent use of PPI and clopidogrel
      or ticlopidine in the well-characterized 1286 patients with CAD undergoing PCI in
      the University of Tokyo Hospital. In the Japanese patients with CAD undergoing
      PCI, the concurrent use of PPI was significantly associated with increased risk
      for major adverse cardiovascular events in the ticlopidine users (hazard ratio
      2.63; 95 % confidence interval 1.65-4.18; P < 0.001), but not in the clopidogrel
      users. In the clopidogrel users as well as the ticlopidine users, PPI use did not
      affect the occurrence of target lesion revascularization, but significantly
      increased the risk for new lesion formation in the coronary arteries, which
      required subsequent revascularization. The adverse cardiovascular effects of the
      concurrent use of PPI and ticlopidine were identified in the patients with CAD
      undergoing PCI. Also, new lesion formation in the coronary arteries was shown to
      be increased when PPI was coprescribed for the thienopyridine users.

PMID- 22460242
TI  - Comparative extrapyramidal effects of Rauwolfia vomitoria, chlorpromazine and
      reserpine in mice.
AB  - Most antipsychotics interfere with the dopaminergic system, resulting in
      extrapyramidal effects. This study compared the extrapyramidal effects of
      chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid
      reserpine (Res), used as antipsychotics, in mice. Ninety age-matched male CD-1
      strain of mice (25-33 g body weight) were divided into 3 groups, each consisting
      of 5 subgroups (n = 6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) was
      administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.)
      and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h before
      testing. Locomotor behaviour (open field test) and motor coordination
      (acceleratory rotarod) were assessed. Mice were also observed for 10 min for
      tremor and vacuous chewing movement (VCM). CPZ and Res dose-dependently decreased
      locomotor behaviour and impaired motor coordination (p < 0.01). RV also decreased
      locomotor behaviour (4.0 mg/kg; p < 0.05) but had minimal effect on motor
      coordination. VCM was lower in the RV group (0.17 +/- 0.16/10 min) than the Res
      (6.8 +/- 1.36/10 min) and Cpz groups (7.83 +/- 1.95/10 min): F ((4,25)) = 10.703;
      p < 0.01. The frequency of bouts of tremor was also lower in the RV group (1.17
      +/- 0.72/10 min) than the Res (21.2 +/- 5.63/10 min) and Cpz (7.83 +/- 1.59/10
      min) groups: F ((4,25)) = 11.012; p < 0.001. The root bark extract of R.
      vomitoria, therefore, has great potential in the management of psychotic
      disorders.

PMID- 22460243
TI  - ALOX5AP gene variants show differential association with coronary artery disease
      in different populations.
AB  - Coronary artery disease (CAD) is a complex disease with various components,
      genetic as well as environmental. Previous reports correlating ALOX5AP gene
      variants and CAD showed conflicting results depending on the population studied.
      In this study, we examined the contribution of ALOX5AP genetic predisposition to
      CAD in a group of CAD patients and controls carefully selected from the Lebanese
      population. We genotyped SNPs for ALOX5AP variants in 289 catheterized patients
      aged <=52 years with >50% stenosis in at least one main coronary artery and 227
      catheterized control subjects aged 60 years and above with 0% stenosis. Chi
      square (chi (2)) tests and logistic regression showed no significant difference
      in the allele and genotype frequencies between the CAD or myocardial infarction
      (MI) cases and the healthy controls. Haplotype analysis using PHASE showed that
      the distribution of the risk haplotypes among cases and controls were not
      significantly different and had no attributable risk to CAD (P = 1.00 and P =
      0.5, respectively) or MI (P = 0.2 and P = 0.5, respectively). Our data revealed
      that ALOX5AP gene variants are not predictors of CAD risk or MI risk among
      Lebanese patients.

PMID- 22460244
TI  - Genetic diversity of hemoglobinopathies, G6PD deficiency, and ABO and Rhesus
      blood groups in two isolates of a primitive Kharia Tribe in Sundargarh District
      of Northwestern Orissa, India.
AB  - Tribal communities constitute about 8.2% of the total population of India. Their
      health needs are even larger than elsewhere in India; this study investigates the
      genetic diversity in relation to hemoglobinopathies, G6PD deficiency and, ABO and
      Rhesus (D) blood groups in two sects, i.e. Dudh (converted Christian) and Dhelki
      (Hinduised) Kharia, a primitive tribe in Sundargarh district of Orissa in Central
      Eastern India. A randomized screening of 767 Kharia tribals (377 males and 390
      females) belonging to all age groups and both sexes was done. Laboratory analysis
      was carried out following the standard methodology and techniques. Contrasting
      differences were observed in the frequency of hematological genetic disorders
      such as beta-thalassemia, sickle cell, hemoglobin E, G6PD deficiency, ABO and
      Rhesus (D) blood groups between the two subgroups. Dudh Kharia had no hemoglobin
      variant allele other than the high prevalence of beta-thalassemia trait (8.1%),
      whereas, their counterpart Dhelki Kharia had the high prevalence of sickle cell
      allele (12.4%), hemoglobin E allele (3.2%), and beta-thalassemia allele (4.0%).
      Frequency distribution of hemoglobin variants between Dudh and Dhelki Kharia
      tribe was statistically highly significant (p < 0.001). High G6PD deficiency was
      detected 19.2% and 30.7% in Dudh Kharia and Dhelki Kharia, respectively (p <
      0.001), the average being 24.4% in Kharia tribe. Kharia tribes show a trend for
      replacement of sickle cell gene with G6PD-deficiency gene as the clinical
      manifestations of G6PD deficiency are mild (do not result in a complete loss of
      enzyme activity) against the sickle cell disease with high morbidity and
      mortality. Rhesus (D)-negative blood group was 1.1% in Dudh Kharia and absent in
      Dhelki Kharia (p < 0.05). This study showed genetic isolation of the two sects of
      Kharia tribe. Antimalarial drugs administration needs to be done with caution.
      Hematological disorders pose a major health challenge having multifaceted
      implications in public health genetics.

PMID- 22460245
TI  - Prospective experience with contingent screening strategy for Down syndrome in
      Estonia.
AB  - The purpose of this study was to establish the first-trimester screening for Down
      syndrome (DS) in Estonia and to evaluate the potential of a contingent screening
      in the population of pregnant women. A prospective cohort study included non
      selected pregnancies during the programme of first-trimester screening for DS in
      a 4-year period at a single centre. The following screening tests were evaluated:
      measurement of nuchal translucency (NT) and serum screening [pregnancy-associated
      plasma protein A and free beta subunit of human chorionic gonadotropin (fbeta
      HCG)]; results were given as combined screening. After first-trimester screening,
      contingent screening protocol was used, and women were divided into three groups:
      high risk, low risk and an intermediate risk group. In the last group, a second
      trimester triple test (AFP; total HCG and uE3) was also performed. The study
      group consisted of 3,194 non-selected pregnancies. In 1,387 (43.4%) women, first
      trimester serum screening showed low risk (risk <= 1:5,000), and no future
      testing was performed, in 30 (0.9%) women screening test showed high risk (risk
      >= 1:50) and a diagnostic test was offered, and in 1,777 (55.7%) women repeated
      risk calculation in the second trimester was done. During the study period, there
      were 17 cases of trisomy 21, of which 15 (88.3%) were detected with the described
      screening programme. In conclusion, two-step contingent sequential screening is a
      better choice for Down syndrome screening in Estonia instead of previously used
      second-trimester screening, and it offers the advantage of earlier diagnosis.

PMID- 22460246
TI  - Influence of genetic variants in the apolipoprotein A5 and C3 gene on lipids,
      lipoproteins, and its association with coronary artery disease in Indians.
AB  - Indians worldwide demonstrate a triad of elevated triglyceride (TG) with high low
      density lipoprotein cholesterol and low high-density lipoprotein cholesterol
      levels. In the present study, we aim to investigate the effect of -1131T > C, -3A
      > G, c.56 C > G, and c.553 G > T SNPs in the apolipoprotein A5 (APOA5) gene and
      1100C > T and 3238C > G in the apolipoprotein C3 (APOC3) on plasma lipid and
      lipoprotein levels and risk of coronary artery disease (CAD) in Indians.
      Genotyping and lipid assays were carried out using standard protocols in a study
      population that included 150 controls and 90 cases with CAD. Significant
      associations between minor alleles and higher TG levels were seen for -1131T > C
      (P < 0.001), -3A > G (P < 0.001), c.56C > G (P = 0.026), and c.553G > T (P =
      0.003) SNPs in the APOA5 gene and 1100C > T (P = 0.001) and 3238C > G (P = 0.009)
      in the APOC3 gene. The haplotypes 11211, 22111, 11112, and 22112 were
      significantly associated with TG levels (P = 0.025, P = 0.017, P = 0.027, and P <
      0.001, respectively) and very-low-density lipoprotein cholesterol levels (P =
      0.025, P = 0.017, P < 0.001, and P = 0.002) in males. The 22111, 11112, and 22112
      were associated with elevated TG (P = 0.030, P = 0.036, and P = 0.024) but not
      VLDL-C levels in females. No association with other lipid parameters was seen. In
      the logistic regression model, the rare S2 allele was a significant risk factor
      (P = 0.030, 95% CI 1.186-31.432) along with smoking (P < 0.0001, 95% CI 2.018
      10.397) for CAD. The APOA5 and APOC3 locus is a strong determinant of plasma TG
      levels in Indians. The APOC3 3238G is a risk factor for CAD and a higher
      frequency was also seen with type 2 diabetes mellitus.

PMID- 22460247
TI  - A descriptive profile of beta-thalassaemia mutations in India, Pakistan and Sri
      Lanka.
AB  - Thalassaemia is a common and debilitating autosomal recessive disorder affecting
      many populations in South Asia. To date, efforts to create a regional profile of
      beta-thalassaemia mutations have largely concentrated on the populations of
      India. The present study updates and expands an earlier profile of beta
      thalassaemia mutations in India, and incorporates comparable data from Pakistan
      and Sri Lanka. Despite limited data availability, clear patterns of historical
      and cultural population movements were observed relating to major beta
      thalassaemia mutations. The current regional mutation profiles of beta
      thalassaemia have been influenced by historical migrations into and from the
      Indian sub-continent, by the development and effects of Hindu, Buddhist, Muslim
      and Sikh religious traditions, and by the major mid-twentieth century population
      translocations that followed the Partition of India in 1947. Given the resultant
      genetic complexity revealed by the populations of India, Pakistan and Sri Lanka,
      to ensure optimum diagnostic efficiency and the delivery of appropriate care, it
      is important that screening and counselling programmes for beta-thalassaemia
      mutations recognise the underlying patterns of population sub-division throughout
      the region.

PMID- 22460248
TI  - Accuracy assessment of pharmacogenetic algorithms for warfarin dose prediction in
      Chinese patients.
AB  - A few warfarin pharmacogenetic dosing algorithms have been proposed,based on
      multiethnic or homogeneous populations, to estimate warfarin therapeutic doses.
      However, it remains to be proven that which algorithm is accurate in predicting
      warfarin dose in Chinese people. We selected eight warfarin dose predictive
      pharmacogenetic algorithms and retrospectively assessed the predictive accuracy
      of each algorithm in a total of 368 eligible outpatients by comparing the actual
      stable therapeutic dose to the dose predicted by the algorithm. Our results
      showed that a high level of performance was demonstrated by three algorithms,Gage
      et al., Anderson et al., and Wu et al., having a similar performance in
      coefficient of determination (R2) and percentage of patients predicted dose
      within 20% of actual dose. The Gage et al. algorithm had the lowest mean absolute
      error (MAE). These results indicated that the algorithm by Gage et al. provided a
      more accurate prediction than did the others,which suggests that this
      pharmacogenetic algorithm might be used in clinical practice to guide rational
      administration of warfarin.

PMID- 22460249
TI  - Association of mesenchymal stem cells with platelet rich plasma on the repair of
      critical calvarial defects in mice.
AB  - PURPOSE: To evaluate the effects of mesenchymal stem cells (MSC) from eight mice
      C57BL/6 gfp(+) bone marrows expanded in cultures associated with platelets rich
      plasma (PRP) deriving from another eight mice, in the repair of critical defects
      in calvarial bone produced in twenty-four adult isogenic mice C57BL/6. METHODS:
      The animals were submitted to a cranial defect of 6.0mm in diameter and divided
      into two equal experimental groups. Control group did not receive treatment and
      the treated group received a MSC pellet containing 1.0 x 10(7) cells/mL
      associated with 50.0 uL of plasma gel containing 1.0 x 10(9) autologous platelets
      within the defect. RESULTS: In the treated group was observed process of
      angiogenesis and bone repair better than control group. CONCLUSION: Mesenchymal
      stem cells derived from bone marrow of C57BL/6 gfp(+) mice associated with PRP
      gel applied in bone critical defects produced in calvarial contributes positively
      to the process of bone repair.

PMID- 22460250
TI  - Facial symmetry evaluation after experimentally displaced condylar process
      fracture in methotrexate treated rats.
AB  - PURPOSE: To investigate the facial symmetry of high and low dose methotrexate
      (MTX) treated rats submitted to experimentally displaced mandibular condyle
      fracture through the recording of cephalometric measurements. METHODS: One
      hundred male Wistar rats underwent surgery using an experimental model of right
      condylar fracture. Animals were divided into four groups: A - saline solution (1
      mL/week); B - dexamethasone (DEX) (0,15 mg/Kg); C - MTX low dose (3 mg/Kg/week);
      D - MTX high dose (30 mg/Kg). Animals were sacrificed at 1, 7, 15, 30 and 90 days
      postoperatively (n=5). Body weight was recorded. Specimens were submitted to
      axial radiographic incidence, and cephalometric mensurations were made using a
      computer system. Linear measurements of skull and mandible, as well as angular
      measurements of mandibular deviation were taken. Data were subjected to
      statistical analyses among the groups, periods of sacrifice and between the sides
      in each group (alpha=0.05). RESULTS: Animals regained body weight over time,
      except in group D. There was reduction in the mandibular length and also changes
      in the maxilla as well as progressive deviation in the mandible in relation to
      the skull basis in group D. CONCLUSION: Treatment with high dose methotrexate had
      deleterious effect on facial symmetry of rats submitted to experimentally
      displaced condylar process fracture.

PMID- 22460251
TI  - Influence of estrogen deficiency and tibolone therapy on trabecular and cortical
      bone evaluated by computed radiography system in rats.
AB  - PURPOSE: To verify the effects of tibolone administration on trabecular and
      cortical bone of ovariectomized female rats by computed radiography system (CRS).
      METHODS: The experiment was performed on two groups of rats previously
      ovariectomized, one received tibolone (OVX+T) while the other did not (OVX),
      those groups were compared to a control group (C) not ovariectomized. Tibolone
      administration (1mg/day) began thirty days after the ovariectomy and the
      treatment remained for five months. At last, the animals were euthanized and
      femurs and tibias collected. Computed radiographies of the bones were obtained
      and the digital images were used to determine the bone optical density and
      cortical thickness on every group. All results were statistically evaluated with
      significance set at P<0.05%. RESULTS: Tibolone administration was shown to be
      beneficial only in the densitometric analysis of the femoral head, performing
      higher optical density compared to OVX. No difference was found in cortical bone
      thickness. CONCLUSION: Ovariectomy caused bone loss in the analyzed regions and
      tibolone administered in high doses over a long period showed not to be fully
      beneficial, but preserved bone mass in the femoral head.

PMID- 22460252
TI  - Analysis of the physical activity effects and measurement of pro-inflammatory
      cytokines in irradiated lungs in rats.
AB  - PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective
      elements, by measuring the radio-induced activation of pro-inflammatory cytokines
      as interleukin-6 (il-6), transforming growth factor -beta (tgf -beta), tumor
      necrosis factor -alpha (tnf-alpha) and protein beta kinase beta (ikkbeta),
      through western blotting analysis. METHODS: A randomized study with 28 Wistar
      hannover rats, males, with a mean age of 90 days and weighing about 200 grams.
      The animals were divided into three groups: (GI, GII and GIII). GIII group were
      submitted to swimming for eight weeks (zero load, three times a week, about 30
      minutes). Then, the groups (except the control group) were submitted to
      irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All
      animals were sacrificed by overdose of pentobarbital, according to the time for
      analysis of cytokines, and then a fragment of the lower lobe of the right lung
      went to western blotting analysis. RESULTS: The cytokines IKK beta, TNF-alpha and
      IL-6 induced by radiation in the lung were lower in the exercised animals.
      However, exercise did not alter the radiation-induced increase in tgf-beta.
      CONCLUSION: The results show a lower response in relation to inflammatory
      cytokines in the group that practiced the exercise pre-radiotherapy, showing that
      exercise can protect tissues from tissue damage due to irradiation.

PMID- 22460253
TI  - Laparoscopic nephrectomy with single-portal access Sitracc(r) in swines.
AB  - PURPOSE: To analyze the viability of using SITRACC((r)) (single-portal access) to
      make partial or total nephrectomy in pigs and also to describe the technical
      difficulties found during these surgical procedures. METHODS: Ten pigs (Landrace
      specie) with 20 kg in average were distributed in two groups: Group A - total
      right nephrectomy - and Group B - partial left nephrectomy -. The anesthetic
      procedure was initially done with thiopental (10 mg/kg) and maintained with
      halothane. The surgical procedures were performed inside the Surgical Technique
      Room from Pontifical Catholic University of Parana (PUCPR). RESULTS: It was
      analyzed the surgery duration, time to insert SITRACC((r)), the volemic loss and
      the size of the organ. In the first surgeries, the surgical time and blood volume
      loss were higher (between 15 to 43 minutes and 120 to 400 mL, respectively). The
      more the procedure was performed, the more the surgeons were used to the
      technique, so the bleeding and the time of surgery was significantly reduced to
      15 minutes and 50 mL of blood loss, respectively. The difficulties found were
      associated with the nippers, however that was not relevant for the surgical
      technique. It was also found that the intra-body suture caused an expressive
      volemic loss. CONCLUSION: The total and partial nephrectomy through umbilical
      single-access by using SITRACC((r)) was feasible and safe in pigs.

PMID- 22460255
TI  - Abnormalities of digestive tract innervation in rat fetus treated with
      ethylenethiourea.
AB  - PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus
      lesions remains imperfectly understood. Such abnormalities have been correlated
      with subocclusive intestinal conditions in children with Hirschsprung's disease,
      cases of chronic constipation and, postoperatively, in cases of anorectal
      anomalies. This study evaluated abnormalities of the myenteric plexus in fetus
      from female rats that received ethylenethiourea. METHODS: Female rats were
      exposed to ethylenethiourea on the 11(th) day of pregnancy (experimental group)
      or to 0.9% physiological solution (control group). Abnormalities were only found
      in the experimental group. The digestive tract muscle layer was analyzed
      morphometrically and changes to the frequencies of nerve plexus cells and
      interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100
      protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and
      skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent
      tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5%
      and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a
      thinner muscle layer associated with lower frequencies of ganglion cells and
      interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe
      nerve plexus abnormalities associated with muscle layer atrophy were observed
      throughout the gastrointestinal tract in newborn rats exposed to
      ethylenethiourea.

PMID- 22460254
TI  - Intestinal healing in rats submitted to ethanol ingestion.
AB  - PURPOSE: To study the effect of alcoholism on intestinal healing and
      postoperative complications in rats METHODS: One hundred and sixty rats were
      divided into two groups: control and treated. The control group received water
      and the treated group 30% ethanol. After 180 days, colotomy with anastomosis were
      performed. After, the groups were divided into four subgroups: 20 rats for study
      at the following moments: 4(th), 7(th), 14(th) and 21(st) postoperative. The
      analyzed parameters were: weight gain, breaking strength, tissue hydroxyproline,
      postoperative complications and histopathological study RESULTS: Weight gain was
      greater in the control group (p<0.05). When all the subgroups were clustered,
      breaking strength was significantly greater in the control (p<0.05).
      Histopathology and hydroxyproline dosage did not show differences. There were
      five surgical site infections in the treated group while the control group showed
      two (p>0.05). Nine fistulas occurred in the treated group whereas the control
      group two (p<0.05). There were three deaths in the control group and seven in the
      treated group (p>0.05). CONCLUSIONS: Treated group undergo a malnutrition process
      that is revealed by lower weight gain. Impaired intestinal healing as indicated
      by smaller breaking strength. There were a larger number of postoperative
      complications in the treated animals.

PMID- 22460256
TI  - Cecorraphy in single layer using polypropylene and poliglecaprone 25 threads:
      comparative study in rats.
AB  - PURPOSE: To compare sutures with polypropylene and poliglecaprone 25 after
      partial cecotomy in rats. METHODS: Thirty six rats divided into two groups, A and
      B, of 18 animals; each group was also divided into three subgroups of six animals
      sacrificed at 4(th), 7(th) and 14(th) days after surgery. Were studied the
      mortality, morbidity, complications attributable to sutures, macroscopy, optical
      microscopy and measurement of hydroxyproline at the level of the suture. RESULTS:
      There were no deaths or wound complications such as hematoma, seroma, abscess,
      evisceration or eventration. On microscopic evaluation reepithelization,
      coaptation and inflammation in both groups did not differ significantly. The
      average rate of tissue hydroxyproline found in the samples on the 4(th) day after
      surgery, was 21.38 mg/g tissue for group A and 16.68 mg/g for group B; on day 7
      after surgery, the average was 15.64 mg/g tissue for group A and 26.53 mg/g for
      group B; on day 14, the average was 8.09 mg/g tissue for group A and 25.07 mg/g
      for group B. CONCLUSION: There were no differences on clinical evolution,
      macroscopic aspect, microscopic data and hydroxyproline concentration on both
      sutures.

PMID- 22460257
TI  - Mechanical properties of radial bone defects treated with autogenous graft
      covered with hydroxyapatite in rabbit.
AB  - PURPOSE: To determine biomechanical property of autogenous bone graft covered
      with hydroxyapatite in the defect of radial bone in rabbit. METHODS: Eighteen
      adult male New Zealand white rabbits were used which were divided into three
      groups (I, II, III) of six rabbits each. A segmental bone defect of 10 mm in
      length was created in the middle of the right radial shaft under general
      effective anesthesia in all rabbits and were stabilized using mini-plate with
      four screws. The defects In group I were left as such without filler, whereas in
      group II the defect were filled up with harvested 10 mm rib bone and in group III
      the defect were packed with rib bone covered with nano-hydroxyapatite. All
      rabbits in three groups were divided into two subgroups (one month and three
      months duration with three rabbits in each one). RESULTS: The mechanical property
      and the mean load for fracturing normal radial bone was recorded 388.2 +/- 6 N
      whereas it was 72.4 +/- 12.8 N for group I in 1 month duration which was recorded
      182.4 +/- 14.2 N for group II and 211.6 +/- 10.4 N for group III at the end of 1
      month. These values were 97.6 +/- 10.2 N for group I and 324.6 +/- 8.2 N for
      group II and 372.6 +/- 17.4 N for group III at the end of three months after
      implantation. CONCLUSION: Implantation of autologous graft covered with
      hydroxyapatite indicated to have positive effect in integral formation of
      qualitative callus at the site of fracture and early re-organization of callus to
      regain mechanical strength too.

PMID- 22460258
TI  - The embracing end-to-side neurorrhaphy in rats.
AB  - PURPOSE: Compare two new methods with the traditional end-to-side neurorrhaphy.
      METHODS: Rats were divided into four groups. In A-L group the peroneal nerve was
      sectioned and the distal stump was connected to the lateral of the tibial nerve
      (donor) with two 10-0 nylon points. In A-R group two perineurium flaps embraced
      the donor nerve. In the B-R group a suture embraced the donor nerve. Group B-L
      was the control. After six months tibial cranial muscle mass and morphometry of
      the distal stump of the peroneal nerve were evaluated. RESULTS: Muscle mass in
      groups A-R, A-L and B-R were lower than B-L group (p<0.0001) an equal between
      themselves (p>0.05). Groups A-R, B-R and A-L had a lower number of nerve fibers
      when compared with B-L (p=0.0155, p=0.016, p=0.0021). CONCLUSION: The three types
      of neurorrhaphy showed no differences related to muscle mass and number of nerve
      fibers suggesting that the embracing with a single suture has great potential due
      its simplicity and usefulness in deep areas.

PMID- 22460259
TI  - Comparative study on ureteroscopic lithotripsy and laparoscopic ureterolithotomy
      for treatment of unilateral upper ureteral stones.
AB  - PURPOSE: To compare the curative effects of ureteroscopic lithotripsy and
      laparoscopic ureterolithotomy for unilateral upper ureteral stones, and to
      explore optimal surgical indications and skills. METHODS: Fifty cases of
      unilateral upper ureteral stones were randomly divided into two groups: one group
      underwent ureteroscopic holmium laser lithotripsy under epidural or lumbar
      anesthesia (n=25), and another group underwent laparoscopic ureterolithotomy
      under general anesthesia (n=25). Double-J stent was routinely indwelled in both
      groups. Operating time, postoperative hospitalization time, stone clearance rate
      and perioperative complications were compared. RESULTS: Operation was
      successfully performed in all 50 cases, and no open surgery was converted in any
      case. In the ureteroscopy and laparoscopy groups, the mean operating time was
      49.0 +/- 10.7 min and 41.8 +/- 8.0 min (t=2.68, P=0.00999), respectively, their
      hospitalization time was 2.8 +/- 1.3 days vs. 2.9 +/- 0.8 days (t =-0.40,
      P=0.69413), and stone clearance rate was 88.0% (22/25) vs. 100% (25/25). Stone
      moved to the renal pelvis in three cases in the ureteroscopy group, and residual
      stones were removed by extracorporeal shock-wave lithotripsy (ESWL). All patients
      were followed up for more than three months, and no serious complications such as
      ureterostenosis occurred. CONCLUSIONS: Laparoscopic ureterolithotomy has a higher
      stone clearance rate and shorter operation time compared with ureteroscopic
      lithotripsy. Laparoscopic ureterolithotomy is one safe and effective treatment on
      unilateral upper ureteral stones.

PMID- 22460260
TI  - Training on synthetic ethylene-vinyl acetate bench model allows novice medical
      students to acquire suture skills.
AB  - PURPOSE: To assess the acquisition of suture skills by training on ethylene-vinyl
      acetate bench model in novice medical students. METHODS: Sixteen medical students
      without previous surgery experience (novices) were randomly divided into two
      groups. During one hour group A trained sutures on ethylene-vinyl acetate (EVA)
      bench model with feedback of instructors, while group B (control) received a
      faculty-directed training based on books and instructional videos. All students
      underwent a both pre-and post-tests to perform two-and three-dimensional sutures
      on ox tongue. All recorded performances were evaluated by two blinded evaluators,
      using the Global Rating Scale. RESULTS: Although both groups have had a better
      performance (p<0.05) in the post-test when compared with the pre-test, the
      analysis of post-test showed that group A (EVA) had a better performance (p<0.05)
      when compared with group B (control). CONCLUSION: The ethylene vinyl acetate
      bench model allowed the novice students to acquire suture skills faster when
      compared to the traditional model of teaching.

PMID- 22460261
TI  - Fructo-oligosaccharide effects on blood glucose: an overview.
AB  - PURPOSE: To identify the current status of scientific knowledge in fructo
      oligosaccharides (FOS), non-conventional sugars that play an important role in
      glycemia control. METHODS: We performed a search for scientific articles in
      MEDLINE and LILACS databases, from January 1962 to December 2011, using
      English/Portuguese key words: "blood glucose/glicemia", "prebiotics/prebioticos"
      and "dietary fiber/fibras na dieta". From an initial number of 434 references,
      some repeated, 43 references published from 1962 to 2011 were included in this
      study. The selected texts were distributed in three topics: (1) metabolism of
      FOS, (2) FOS and experimental studies involving glucose and (3) human studies
      involving glucose and FOS. RESULTS: Five studies have shown that the use of FOS
      reduces the fecal content and increases intestinal transit time. Experimental
      studies have shown that dietary supplementation with high doses (60 g/Kg) of
      propionate, a short-chain fatty acid decreased glycemia. The use of lower doses
      (3 g/kg) did not produce the same results. Study in subjects with diabetes type
      II showed that the addition of 8 grams of FOS in the diet for 14 days, caused a
      reduction in serum glucose. In another study with healthy subjects, there were no
      changes in glycemic control. CONCLUSIONS: This review demonstrates that
      consumption of FOS has a beneficial influence on glucose metabolism. The
      controversies appear to be due to inadequate methodological designs and/or the
      small number of individuals included in some studies.

PMID- 22460262
TI  - Outcome and prognostic features in adult pineoblastomas: analysis of cases from
      the SEER database.
AB  - BACKGROUND: Adult pineoblastomas (PBL) are rare central nervous system tumors.
      Patient and treatment factors associated with outcome are poorly defined and
      limited to small retrospective case series and single case reports. Using the
      Surveillance, Epidemiology, and End Results (SEER) cancer registry, we
      investigated clinicopathological factors associated with outcome in adult PBL.
      METHODS: Adult patients (>=16 years old) with PBL diagnosed between 1990 and 2007
      were identified from the SEER database. Kaplan-Meier survival analysis and Cox
      models were used to examine the effect of variables on overall survival. The
      variables analyzed included patient's age at diagnosis, gender, race, tumor
      location, uni-focal or multi-focal tumor, tumor size, surgical resection, and the
      use of adjuvant radiotherapy. RESULTS: Ninety-five patients were identified, with
      a median age at diagnosis of 39.2 years. Sixty-one patients (64 %) underwent
      surgery and 44 patients (47.4 %) received adjuvant radiotherapy. Forty-two
      patients (44 %) had both surgery and radiotherapy. The median overall survival
      was 176 months. Univariate analysis identified younger age at diagnosis, uni
      focal and localized disease as important predictors of overall survival. On
      multivariate analysis, only age at diagnosis and localized disease emerged as
      important prognostic factors. CONCLUSIONS: Despite the numerous limitations of
      the SEER database, this study represents the largest analysis of adult PBL to
      date. Clinically relevant prognostic factors were younger age of diagnosis and
      localized disease. The role of surgery and adjuvant radiotherapy remains to be
      defined. Our data suggest these treatment modalities may not influence overall
      survival.

PMID- 22460264
TI  - Homocysteine levels in morbidly obese patients: its association with waist
      circumference and insulin resistance.
AB  - The association between morbid obesity and hyperhomocysteinemia (HH) remains
      controversial and the nature of this relationship needs to be clarified as
      several metabolic, lipidic, inflammatory and anthropometric alterations that
      accompany morbid obesity may be involved. In 66 morbidly obese patients, 47 women
      and 19 men aged 41 +/- 12 years and 66 normo-weight subjects, 43 women and 23
      men, aged 45 +/- 11 years, we determined homocysteine (Hcy) levels along with
      lipidic, anthropometric, inflammatory and insulin resistance markers. In
      addition, we investigated the effect of Metabolic Syndrome (MS) and its
      components on Hcy levels. Obese patients had statistically higher Hcy levels than
      controls: 12.76 +/- 5.30 MUM vs. 10.67 +/- 2.50 MUM; p = 0.006. Moreover,
      morbidly obese subjects showed higher waist circumference, glucose, insulin,
      HOMA, leptin, triglycerides, fibrinogen, C reactive protein (CRP) (p < 0.001,
      respectively), and lower vitamin B12 (p = 0.002), folic acid and HDL-cholesterol
      (p < 0.001, respectively). In the multivariate regression analysis, waist
      circumference, glucose, leptin and folic acid levels were independent predictors
      for Hcy values (p < 0.050). When obese patients were classified as having MS or
      not, no differences in Hcy levels were found between the two groups (p = 0.752).
      Yet when we analysed separately each MS component, only abdominal obesity was
      associated with Hcy levels (p = 0.031). Moreover when considering glucose >110
      mg/dL (NCEP-ATPIII criteria) instead of glucose intolerance >100 mg/dl (updated
      ATPIII criteria), it also was associated with HH (p = 0.042). These results were
      confirmed in the logistic regression analysis where abdominal obesity and glucose
      >115 mg/dL constitute independent predictors for HH (OR = 3.2; CI: 1.23-13.2; p =
      0.032, OR: 4.6; CI: 1.7-22.2; p = 0.016, respectively). The results of our study
      indicate that increased Hcy levels are related mostly with abdominal obesity and
      with insulin resistance. Thus, HH may raise atherothrombotic and thromboembolic
      risk in these patients.

PMID- 22460263
TI  - Endothelin ET(B) receptors are involved in the relaxation to the pig urinary
      bladder neck.
AB  - AIMS: The involvement of endothelin receptors in the contraction of the lower
      urinary tract smooth muscle is well established. There is scarce information,
      however, about endothelin receptors mediating relaxation of the bladder outlet
      region. The current study investigates the possible existence of endothelin ET(B)
      receptors involved in the relaxation of pig bladder neck. METHODS: ET(B) receptor
      expression was determined by immunohistochemistry and urothelium-denuded bladder
      neck strips were mounted in organ baths for isometric force recording. RESULTS:
      ET(B) -immunoreactivity (ET(B) -IR) was observed within nerve fibers among smooth
      muscle bundles and urothelium. BQ3020 (0.01-300 nM), an ET(B) receptor agonist,
      produced concentration-dependent relaxations which were reduced by BQ788, an
      ET(B) receptor antagonist, and by inhibitors of protein kinase A (PKA) and large
      (BK(Ca) )- or small (SK(Ca) )-conductance Ca(2+) -activated K(+) channels.
      Pretreatment with BK(Ca) or SK(Ca) channel inhibitors plus PKA blocking did not
      cause further inhibition compared with that exerted by inhibiting BK(Ca) or
      SK(Ca) channels only. BQ3020-induced relaxation was not modified by blockade of
      either nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX) or of
      intermediate-conductance Ca(2+) -activated-(IK(Ca) ), ATP-dependent-(K(ATP) ), or
      voltage-gated-(K(v) ) K(+) channels. Under non-adrenergic non-cholinergic (NANC)
      conditions, electrical field stimulation (0.5-16 Hz) evoked frequency-dependent
      relaxations, which were reduced by BQ788 and potentiated by threshold
      concentrations of BQ3020. CONCLUSIONS: These results suggest that BQ3020 produces
      relaxation of the pig bladder neck via activation of muscle endothelin ET(B)
      receptors, NO/cGMP- and COX-independent-, cAMP-PKA pathway-dependent-mechanisms,
      and involving BK(Ca) and SK(Ca) channel activation. ET(B) receptors are also
      involved in the NANC inhibitory neurotransmission.

PMID- 22460265
TI  - Use of hydroxyethyl starch for inducing red blood cell aggregation.
AB  - Aggregation of human red blood cells (RBC) remains of biological and clinical
      interest. Replacement of plasma proteins by polymers to induce RBC aggregation
      may help to unravel the fundamentals of the aggregation process. Two theories
      exist to explain RBC aggregation mechanisms: a depletion and a bridging theory.
      RBC aggregation induced by hydroxyethyl starch (HES) increases with polymer size,
      which suggests that aggregation is induced via the bridging theory. In this
      study, the electrophoretic mobility (EPM) was measured to investigate RBC
      aggregation induced by 200 kDa HES polymers. Also, we evaluated if these polymers
      were useful for demonstrating aggregation differences between RBCs from healthy
      and type-1 diabetes mellitus (T1DM) subjects. Our results demonstrate that EPM
      values of RBCs in 200 kDa HES solutions were less negative than could be
      predicted by the viscosity of the suspension, supporting the bridging theory.
      Furthermore, aggregation analysis using the LORCA demonstrated that 200 kDa HES
      solution enhanced RBC aggregation of healthy and diabetic subjects similarly as
      standard 500 kDa dextran solutions. IN CONCLUSION: our data supports the bridging
      mechanism underlying 200 kDa HES induced RBC aggregation. In addition, both
      polymers are useful for demonstrating cellular induced aggregation differences
      between RBCs from healthy and T1DM subjects.

PMID- 22460266
TI  - Automated method for tracking vasomotion of intravital microvascular and
      microlymphatic vessels.
AB  - Dynamic tracking of microvascular and microlymphatic vasomotion presents a
      critical image processing technique in the evaluation of function and dysfunction
      of the microvasculature. Many methods for determination of diameter changes have
      been reported. Previous methods which were specifically developed for vasomotion
      tracking of intravital, fluorescence-free, rapidly constricting microvascular and
      microlymphatic vessels have various limitations due to complex image background,
      vessel wall distortion, image drift, noise and other artifacts. In order to
      overcome these major obstacles and remove undesirable limitations, this study
      proposed a tracking strategy based on feature matching of moving object-VasTrack.
      First, we calculate the image drift vector by feature template matching of a
      landmark in the background. Second, dynamically regulate the position of a sample
      line in accordance with the drift vector for sustaining the consistency of
      measurement location. Third, dynamically recognize and track edge position
      changes by applying feature template matching using edge context. This method
      does not require special preprocessing of video image registration and rotation.
      VasTrack compensates efficiently for image drift and vessel wall distortion, can
      simultaneously track and determine vessel diameters at any orientation and in
      multiple locations. Testing proved that VasTrack is robust and accurate, and will
      satisfy the needs of basic microcirculatory research and clinical inspection.

PMID- 22460267
TI  - Relationship between acute chest syndrome and the sympatho-vagal balance in
      adults with hemoglobin SS disease; a case control study.
AB  - The present study evaluated the relationship between acute chest syndrome (ACS)
      and autonomic nervous system (ANS) activity in patients with hemoglobin SS
      disease (Hb SS). Nine patients had suffered ACS were matched by age and gender to
      patients who had not suffered ACS and ANS activity, pulmonary function and
      history of painful crisis were compared. Correlations between number of episodes
      of ACS suffered and these variables were determined. The results demonstrated
      that 1) patients with a history of ACS ever had lower parasympathetic nervous
      system (PNS) activity and lower global ANS activity than patients with no ACS
      ever (p < 0.05), 2) the number of ACS episodes ever negatively correlated (p <
      0.05) with PNS activity and global ANS activity and 3) There were no significant
      associations between lung function or a history of painful crisis in these
      patients. In conclusion, a history of ACS was associated with ANS dysfunction in
      adults with Hb SS disease.

PMID- 22460268
TI  - Expression of sphingosine 1-phosphate receptor 4 and sphingosine kinase 1 is
      associated with outcome in oestrogen receptor-negative breast cancer.
AB  - BACKGROUND: We previously reported that sphingosine 1-phosphate receptor 4
      (S1P(4)) is expressed and stimulates the ERK-1/2 pathway via a human epidermal
      growth factor receptor 2 (HER2)-dependent mechanism in oestrogen receptor
      negative (ER(-)) MDA-MB-453 breast cancer cells. METHODS: Clinical relevance of
      S1P(4) and sphingosine kinase 1 (SK1, which catalyses the formation of S1P) was
      assessed in a cohort of 140 ER(-) breast tumours by immunohistochemistry (IHC)
      and the weighted histoscore method. Additional evidence for a functional
      interaction between S1P(4) and SK1 and between HER2 and SK1 was obtained using
      MDA-MB-453 cells. RESULTS: High S1P(4) expression is associated with shorter
      disease-free (P=0.014) and disease-specific survival (P=0.004), and was
      independent on multivariate analysis. In addition, patients with tumours that
      contain high and low levels of SK1 and S1P(4), respectively, have a significantly
      shorter disease-free survival (P=0.043) and disease-specific survival (P=0.033)
      compared with patients whose tumours contain both low S1P(4) and SK1 levels. In
      addition, high tumour expression of SK1 was significantly associated with shorter
      disease-specific survival (P=0.0001) in patients with HER2-positive tumours.
      Treatment of MDA-MB-453 cells with the SK1 inhibitor, SKi (2-(p-hydroxyanilino)-4
      (p-chlorophenyl)thiazole) reduced the basal and S1P/S1P(4)-induced activation of
      ERK-1/2 and altered HER2 trafficking in these cells. CONCLUSION: These findings
      highlight an important role for S1P(4) and SK1 in ER(-) breast cancer
      progression.

PMID- 22460269
TI  - Impact of mutant beta-catenin on ABCB1 expression and therapy response in colon
      cancer cells.
AB  - BACKGROUND: Colorectal cancers are often chemoresistant toward antitumour drugs
      that are substrates for ABCB1-mediated multidrug resistance (MDR). Activation of
      the Wnt/beta-catenin pathway is frequently observed in colorectal cancers. This
      study investigates the impact of activated, gain-of-function beta-catenin on the
      chemoresistant phenotype. METHODS: The effect of mutant (mut) beta-catenin on
      ABCB1 expression and promoter activity was examined using HCT116 human colon
      cancer cells and isogenic sublines harbouring gain-of-function or wild-type beta
      catenin, and patients' tumours. Chemosensitivity towards 24 anticancer drugs was
      determined by high throughput screening. RESULTS: Cell lines with mut beta
      catenin showed high ABCB1 promoter activity and expression. Transfection and
      siRNA studies demonstrated a dominant role for the mutant allele in activating
      ABCB1 expression. Patients' primary colon cancer tumours shown to express the
      same mut beta-catenin allele also expressed high ABCB1 levels. However, cell line
      chemosensitivities towards 24 MDR-related and non-related antitumour drugs did
      not differ despite different beta-catenin genotypes. CONCLUSION: Although ABCB1
      is dominantly regulated by mut beta-catenin, this did not lead to drug resistance
      in the isogenic cell line model studied. In patient samples, the same beta
      catenin mutation was detected. The functional significance of the mutation for
      predicting patients' therapy response or for individualisation of chemotherapy
      regimens remains to be established.

PMID- 22460271
TI  - Brominated boron dipyrrins: synthesis, structure, spectral and electrochemical
      properties.
AB  - meso-Anisyl boron dipyrrins (BODIPYs) 1-6 containing one to six bromines at the
      pyrrole carbons have been synthesized by treating meso-anisyl dipyrromethane with
      'n' equivalents of N-bromosuccinimide in THF at room temperature followed by
      oxidation with DDQ, neutralization with triethylamine and further complexation
      with BF(3).OEt(2). The brominated compounds were characterized by HR-MS mass,
      detailed (1)H, (19)F and (11)B NMR and X-ray diffraction studies. The crystal
      structures solved for compounds 2-6 indicate that the boron dipyrrinato framework
      comprised two pyrrole rings and one six membered boron containing ring in one
      plane like other reported BODIPYs. However, the dihedral angle between the BODIPY
      core and the meso-anisyl group varied from 48 degrees  to 88 degrees  and the
      meso-anisyl ring has an almost perpendicular orientation in penta 5 and
      hexabrominated 6 BODIPYs. The absorption and emission studies showed a
      bathochromic shift and reached a maximum for tetrabrominated derivative 4, after
      which there was no change in the peak maxima for penta 5 and hexabrominated 6
      derivatives. However, the quantum yields were reduced with the increasing number
      of bromines. The electrochemical studies revealed that brominated BODIPY
      compounds 1-6 are easier to reduce compared to unsubstituted meso-anisyl BODIPY 8
      and the reduction potential is linearly related to the number of Br groups.

PMID- 22460272
TI  - Management of vaginal intraepithelial neoplasia.
AB  - OBJECTIVES: Vaginal intraepithelial neoplasia (VaIN) accounts for 0.4% of the
      lower genital tract intraepithelial disease. Various treatments have been
      reported often as small case series or reports. MATERIALS AND METHODS: An
      electronic search of the Ovid MEDLINE (from 1948 to present) and PubMed was
      performed, and only articles written in English were reviewed. All articles
      ranging from case reports to randomized controlled trials were included. This
      review critically appraises the published evidence for different treatment
      modalities and gives an overview of these options. RESULTS: The 3 main modalities
      reported were surgery, brachytherapy, and medical management. Surgery included
      local excision, laser ablation, vaginectomy, and cavitational ultrasonic
      ablation. Medical management included topical 5% imiquimod, 5-fluorouracil, and
      tricholoroacetic acid. All treatments had good success rates for disease
      clearance with low rates of progression to cancer. Prerequisites for ablative
      treatments are the lesion is fully visible and adequately examined by biopsy to
      exclude invasion. Where invasion is suspected or cannot be excluded (e.g., at the
      vault suture line), surgical excision is essential. Brachytherapy and
      vaginectomy, although effective, have a limited place because of their related
      morbidity. Treatment choice may depend on the availability of equipment and
      expertise. CONCLUSIONS: Conservative options in the form of laser ablation and
      topical agents are useful as first-line treatment methods especially in young
      women and for multifocal disease. Radical options like brachytherapy and
      vaginectomy should be reserved for highly selected cases. Evidence from a
      randomized controlled trial of first-line treatment with surgical and medical
      therapies is needed to compare treatment success and impact on quality of life.

PMID- 22460270
TI  - Randomised phase II trial of docetaxel and sunitinib in patients with metastatic
      gastric cancer who were previously treated with fluoropyrimidine and platinum.
AB  - BACKGROUND: Docetaxel is widely used as a chemotherapeutic agent for gastric
      cancer treatment. A combined regimen with sunitinib demonstrated a synergistic
      antitumour effect in a preclinical model. The aim of this study was to evaluate
      the efficacy and safety of this combination in patients with unresectable or
      metastatic advanced gastric cancer following failure of treatment with a
      fluoropyrimidine and platinum combination. METHODS: This open-label, phase II,
      randomised trial enrolled patients with unresectable or metastatic gastric
      cancer. Patients were assigned to either a docetaxel monotherapy arm (D only arm:
      60 mg m(-2), every 3 weeks) or a combination arm (DS arm: docetaxel+sunitinib
      37.5 mg every day). The primary end point of the study was time to progression
      and the secondary end points were overall response rate, disease control rate,
      overall survival, and toxicity profile. A pharmacokinetic study was also
      performed. RESULTS: A total of 107 patients were entered into the study. The TTP
      was not significantly prolonged in the DS arm when compared with the D only arm
      (DS vs D only arm: 3.9 months (95% confidence interval (CI) 2.9-4.9) vs 2.6
      months (95% CI 1.8-3.5) (P=0.206). The hazard ratio for TTP was 0.77 (95% CI 0.52
      1.16). However, the objective response rate was significantly higher in the DS
      arm (41.1% vs 14.3%, P=0.002). Patients in the DS arm experienced stomatitis,
      diarrhoea, and hand-foot syndrome more frequently. CONCLUSION: The addition of
      sunitinib to docetaxel did not significantly prolong TTP, although it
      significantly increased response.

PMID- 22460273
TI  - Progression and persistence of low-grade cervical squamous intraepithelial
      lesions in women living with human immunodeficiency virus.
AB  - OBJECTIVE: This study aimed to investigate the progression and persistence of low
      grade squamous intraepithelial lesions (SILs) in human immunodeficiency virus
      (HIV)-infected women. METHODS: Study participants for this retrospective cohort
      study were 1,720 women who had LSIL as their first abnormal Pap smear. A
      comparison of the survival of LSIL without progression to high-grade SIL as
      progression-free time and the survival of SIL without clearance of the lesion as
      persistence of SIL was done for women of HIV-positive, HIV-negative, or unknown
      status using the Kaplan-Meier method. Multivariable Cox proportional hazards
      regression model was applied to identify independent risk factors for disease
      progression or persistence. RESULTS: We found progression of LSIL not different
      between HIV groups but that persistence occurred more in HIV-positive women
      (63.8% vs 35.0%, p < .001). For the HIV group, antiretroviral therapy that was
      started before the first LSIL was associated with decreased risk for progression
      compared with no antiretroviral therapy (hazard ratio = 0.66, 95% CI = 0.54-0.81,
      p < .001). Antiretroviral therapy also improved clearance when corrected for
      excision treatment and age (hazard ratio = 1.71, 95% CI = 1.29-2.27, p < .001).
      Excision of LSIL reduced the risk of progression. In HIV-negative women,
      progression was reduced from 54.7% to 0.0% (p < .001), and from 46.9% to 6.4% in
      HIV-positive women (p < .001). Excision also reduced persistence in HIV-negative
      women from 39.5% to 7.1% (p = .001), but for HIV-positive women, the effect was
      smaller (from 66.3% to 45.5%, p < .001). CONCLUSIONS: Antiretroviral treatment
      reduced the risk for progression and persistence of LSIL in HIV-infected women.

PMID- 22460274
TI  - Vaginal polypoid endometriosis simulating neoplasia in a young woman.
AB  - OBJECTIVE: The study aimed to describe a case of vaginal polypoid endometriosis
      and its management. MATERIALS AND METHODS: This study is a case report. The
      patient was a nulliparous woman aged 27 years who presented with pain in her
      lower abdomen and continuous bleeding per vaginum for 2 months. On speculum
      examination, multiple, smooth, polypoid masses were seen arising all around the
      vaginal fornices; cervix was healthy. Ultrasound revealed a bulky uterus with a 5
      * 6-cm fibroid in the posterior wall with echogenic area adjacent to cervix and
      gross left hydroureteronephrosis. The right kidney was removed 6 years consequent
      to pyonephrosis. Biopsy of the vaginal polypoidal mass was reported as vaginal
      polypoid endometriosis. The patient was planned for myomectomy and vaginal mass
      excision. On examination under anesthesia, the base of polypoid mass was thick
      and fixed and could not be excised completely. Myomectomy was done.
      Postoperatively, the patient received 3 injections of gonadotropin-releasing
      hormone agonist, but the size of the mass did not decrease. She was then planned
      for ureteric reimplantation and panhysterectomy. Hysterectomy was not possible
      because of extensive parametrial involvement, but Boari flap ureteric
      implantation with bilateral salpingo-oophorectomy was done. RESULTS: Vaginal
      polypoid endometriosis did not respond to medical treatment. However, the
      widespread vaginal polypoidal masses regressed significantly after oophorectomy.
      CONCLUSION: Bilateral oophorectomy was resorted to as an option in this case of
      vaginal polypoid and extensive pelvic endometriosis not amenable to medical
      treatment and surgical excision.

PMID- 22460275
TI  - Vulvar intraepithelial neoplasia:  evaluation of treatment modalities.
AB  - OBJECTIVE: The study aimed to evaluate effectiveness and recurrence rate of
      vulvar intraepithelial neoplasia (VIN) treatment according to treatment
      modalities as follows: imiquimod (Aldara), laser ablation, laser excision, wide
      local excision, and skinning vulvectomy. It also aimed to analyze risk factors
      associated to VIN recurrence. MATERIALS AND METHODS: Between January 1997 and
      December 2010, 29 women were treated and followed up for VIN in our center.
      Demographics, risk factors, treatment modality, effectiveness, and recurrence
      data were recorded retrospectively. Study analysis used Student t test and chi2
      test. RESULTS: The median age was 52 years (range = 22-77 years); 52% were
      smokers, 31% were immunosuppressed, and 34% had concomitant or previous lower
      genital tract dysplasia. Of all patients, 38% had laser ablation, 31% had laser
      excision, 24% had wide local excision, and 3% had vulvectomy and imiquimod, with
      86.2% overall effectiveness and 20% recurrence (2 laser excision and 2 wide local
      excision), within a mean of 35 months. CONCLUSIONS: Excisional treatment has
      diagnostic and treatment advantages in VIN lesions. The goal is to prevent
      development of invasive vulvar cancer while preserving normal vulvar anatomy and
      function.

PMID- 22460276
TI  - Cutaneous vulvar streptococcal infection.
AB  - OBJECTIVE: This study aimed to determine the etiology of fine superficial
      fissures in women with vulvar pain. MATERIALS AND METHODS: The charts of women
      with vulvar complaints seen in the Mucosal Disorders Clinic at Northwestern
      University between April 2006 and May 2008 were reviewed. Outcome measures
      included mucocutaneous examination findings and results of microbiological swab
      cultures in the presence of fine, superficial, vulvar and/or perianal fissures.
      The presence of concomitant vulvar disorders was noted. RESULTS: Sixteen women
      who presented with vulvar pain were found to have fine, superficial, vulvar
      and/or perianal fissures with minimal or no erythema on examination. None had
      inflammatory vaginitis. Group B beta-hemolytic streptococcus (Streptococcus
      agalactiae) was recovered in 6 (37.5%) patients. All women with group B beta
      hemolytic streptococcus-positive cultures had a concomitant vulvar disorder;
      however, fissures were present despite appropriate treatment directed at the
      concomitant vulvar dermatosis. Three patients reported improvement in vulvar pain
      after treatment with antibiotics, and fissures had resolved by the time of follow
      up examination in these 3 patients. CONCLUSIONS: Group B beta-hemolytic
      streptococcus may cause painful fine superficial fissures and minimal erythema of
      vulvar skin. Obtaining microbiological cultures should be considered in the
      evaluation of vulvar pain even in the absence of purulent inflammatory vaginitis.
      The search for documentation and treatment of this relevant pathogen is a
      departure from published recommendations.

PMID- 22460277
TI  - Technical note: Criterion validity of whole body surface area equations: a
      comparison using 3D laser scanning.
AB  - Measurements of whole body surface area (WBSA) have important applications in
      numerous fields including biological anthropology, clinical medicine,
      biomechanics, and sports science. Currently, WBSA is most often estimated using
      predictive equations due to the complex and time consuming methods required for
      direct measurement. The main aim of this study was to identify whether there were
      significant and meaningful differences between WBSA measurements taken using a
      whole body three-dimensional (3D) scanner (criterion measure) and the estimates
      derived from each WBSA equation identified from a systematic review. The study
      also aimed to determine whether differences varied according to body mass index
      (BMI), sex, or athletic status. Fifteen WBSA equations were compared with direct
      measurements taken on 1,714 young adult subjects, aged 18-30 years, using the
      Vitus Smart 3D whole body scanner, including 1,452 subjects (753 males, 699
      females) from the general Australian population and 262 rowers (148 males, 114
      females). Mixed-design analysis of variances determined significant differences
      and accuracy was quantified using Bland-Altman analysis and effect sizes.
      Thirteen of the 15 equations overestimated WBSA. With a few exceptions, equations
      were accurate with a low-systematic error (bias <=2%) and low-random error
      (standard deviation of the differences 1.5-3.0%). However, BMI did have a
      substantial impact with the accuracy of some WBSA equations varying between the
      four BMI categories. The Shuter and Aslani: Eur J Appl Physiol 82 (2000) 250-254
      equation was identified as the most accurate equation and should be used for
      Western populations 18-30 years of age. Care must be taken when deciding which
      equation to use when estimating WBSA.

PMID- 22460278
TI  - Mitochondrial involvement to methylglyoxal detoxification: D-Lactate/Malate
      antiporter in Saccharomyces cerevisiae.
AB  - Research during the last years has accumulated a large body of data that suggest
      that a permanent high flux through the glycolytic pathway may be a source of
      intracellular toxicity via continuous generation of endogenous reactive
      dicarbonyl compound methylglyoxal (MG). MG detoxification by the action of the
      glyoxalase system produces D-lactate. Thus, this article extends our previous
      work and presents new insights concerning D-lactate fate in aerobically grown
      yeast cells. Biochemical studies using intact functional mitochondrial
      preparations derived from Saccharomyces cerevisiae show that D-lactate produced
      in the extramitochondrial phase can be taken up by mitochondria, metabolised
      inside the organelles with efflux of newly synthesized malate. Experiments were
      carried out photometrically and the rate of malate efflux was measured by use of
      NADP(+) and malic enzyme and it depended on the rate of transport across the
      mitochondrial membrane. It showed saturation characteristics (K(m) = 20 MUM;
      V(max) = 6 nmol min(-1) mg(-1) of mitochondrial protein) and was inhibited by
      alpha-cyanocinnamate, a non-penetrant compound. Our data reveal that reducing
      equivalents export from mitochondria is due to the occurrence of a putative D
      lactate/malate antiporter which differs from both D-lactate/pyruvate antiporter
      and D-lactate/H(+) symporter as shown by the different V(max) values, pH profile
      and inhibitor sensitivity. Based on these results we propose that D-lactate
      translocators and D-lactate dehydrogenases work together for decreasing the
      production of MG from the cytosol, thus mitochondria could play a pro-survival
      role in the metabolic stress response as well as for D-lactate-dependent
      gluconeogenesis.

PMID- 22460279
TI  - Host defence peptides: antimicrobial and immunomodulatory activity and potential
      applications for tackling antibiotic-resistant infections.
AB  - The rapidly increasing incidence of multidrug-resistant infections and the
      alarmingly low rate of discovery of conventional antibiotics create an urgent
      need for alternative strategies to treat bacterial infections. Host defence
      peptides are short cationic molecules produced by the immune systems of most
      multicellular organisms; they are a class of compounds being actively researched.
      In this review, we provide an overview of the antimicrobial and immunomodulatory
      activities of natural host defence peptides, and discuss strategies for creating
      artificial derivatives with improved biological and pharmacological properties,
      issues of microbial resistance, and challenges associated with their adaptation
      for clinical use.

PMID- 22460280
TI  - Migrants and emerging public health issues in a globalized world: threats, risks
      and challenges, an evidence-based framework.
AB  - International population mobility is an underlying factor in the emergence of
      public health threats and risks that must be managed globally. These risks are
      often related, but not limited, to transmissible pathogens. Mobile populations
      can link zones of disease emergence to lowprevalence or nonendemic areas through
      rapid or high-volume international movements, or both. Against this background of
      human movement, other global processes such as economics, trade, transportation,
      environment and climate change, as well as civil security influence the health
      impacts of disease emergence. Concurrently, global information systems, together
      with regulatory frameworks for disease surveillance and reporting, affect
      organizational and public awareness of events of potential public health
      significance. International regulations directed at disease mitigation and
      control have not kept pace with the growing challenges associated with the
      volume, speed, diversity, and disparity of modern patterns of human movement. The
      thesis that human population mobility is itself a major determinant of global
      public health is supported in this article by review of the published literature
      from the perspective of determinants of health (such as genetics/biology,
      behavior, environment, and socioeconomics), population-based disease prevalence
      differences, existing national and international health policies and regulations,
      as well as inter-regional shifts in population demographics and health outcomes.
      This paper highlights some of the emerging threats and risks to public health,
      identifies gaps in existing frameworks to manage health issues associated with
      migration, and suggests changes in approach to population mobility,
      globalization, and public health. The proposed integrated approach includes a
      broad spectrum of stakeholders ranging from individual health-care providers to
      policy makers and international organizations that are primarily involved in
      global health management, or are influenced by global health events.

PMID- 22460281
TI  - Modeling vaccination campaigns and the Fall/Winter 2009 activity of the new
      A(H1N1) influenza in the Northern Hemisphere.
AB  - The unfolding of pandemic influenza A(H1N1) for Fall 2009 in the Northern
      Hemisphere is still uncertain. Plans for vaccination campaigns and vaccine trials
      are underway, with the first batches expected to be available early October.
      Several studies point to the possibility of an anticipated pandemic peak that
      could undermine the effectiveness of vaccination strategies. Here, we use a
      structured global epidemic and mobility metapopulation model to assess the
      effectiveness of massive vaccination campaigns for the Fall/Winter 2009.
      Mitigation effects are explored depending on the interplay between the predicted
      pandemic evolution and the expected delivery of vaccines. The model is calibrated
      using recent estimates on the transmissibility of the new A(H1N1) influenza.
      Results show that if additional intervention strategies were not used to delay
      the time of pandemic peak, vaccination may not be able to considerably reduce the
      cumulative number of cases, even when the mass vaccination campaign is started as
      early as mid-October. Prioritized vaccination would be crucial in slowing down
      the pandemic evolution and reducing its burden.

PMID- 22460282
TI  - In the name of the greater good?
AB  - In the event of a pandemic that poses widespread infection and high death rates,
      the utilitarian mandate to 'reduce harm' is the relevant moral value that trumps
      other ethical considerations. The primacy of a utilitarian approach dictates that
      those who are in a position to assist the cessation of the most serious outbreaks
      in whatever role they may have, must be present to provide their services, and
      those who administer health care must also be present to ensure that all
      responders are supported and protected to the highest degree.

PMID- 22460283
TI  - Preparedness planning for pandemic influenza among large US maternity hospitals.
AB  - The objective of this investigation was to determine the state of pandemic
      influenza preparedness and to delineate commonly reported challenges among a
      sample of larger US national maternity hospitals. This was done given the recent
      emphasis on hospital disaster planning and the disproportionate morbidity and
      mortality that pregnant women have suffered in previous influenza pandemics. An
      internet-based survey was sent to all 12 members of the Council of Women's and
      Infants' Specialty Hospitals. Questions addressed hospital demographics and
      overall pandemic preparedness planning, including presence of a pandemic planning
      committee and the existence of written plans addressing communications, surge
      capacity, degradation of services, and advance supply planning. Nine of 12 (75%)
      hospitals responded. All had active pandemic planning committees with identified
      leadership. The majority (78%) had written formal plans regarding back-up
      communications, surge/overflow capacity, and degradation of services. However,
      fewer (44%) reported having written plans in place regarding supply
      line/stockpiling of resources. The most common challenges noted were staff and
      supply coordination, ethical distribution of limited medical resources, and
      coordination with government agencies. In conclusion, the majority of the Council
      of Women's and Infants' Specialty Hospitals maternity hospitals have preliminary
      infrastructure for pandemic influenza planning, but many challenges exist to
      optimize maternal and fetal outcomes during the next influenza pandemic.

PMID- 22460284
TI  - Emerging aspects of assessing lead poisoning in childhood.
AB  - This review covers the epidemiology of lead poisoning in children on a global
      scale. Newer sources of lead poisoning are identified. The methods that are used
      to assess a population of children exposed to lead are discussed, together with
      the ways of undertaking an exposure risk assessment; this includes assessing the
      time course and identifying sources of lead exposure. Human assessment measures
      for lead toxicity, such as blood lead concentrations, deciduous tooth lead, and
      use of zinc protoporphyrin estimations are evaluated. The role of isotopic
      fingerprinting techniques for identifying environmental sources of exposure is
      discussed. Among emerging data on the cognitive and behavioral effects of lead on
      children, the review considers the growing evidence of neurocognitive dysfunction
      with blood lead concentrations even below 10 ug/dl. The challenge of assessing
      and explaining the risk that applies to an individual as opposed to a population
      is discussed. Intervention strategies to mitigate risk from lead are examined
      together with the limited role for and limitations of chelation therapy for lead.
      Lessons learned from managing a population lead-dust exposure event in Esperance,
      Western Australia in 2007 are discussed throughout the review.

PMID- 22460285
TI  - The health consequences of economic crises.

PMID- 22460286
TI  - Emerging aspects of mobile phone use.
AB  - The mobile phone is a modern-day invention, which has managed to reach many parts
      of the world enabling telecommunications across areas where it was not possible
      before. Although these devices have proved to be life saving in certain
      circumstances (e.g., after accidents) and helped improve the quality of life in
      some sectors, concerns continue to be raised about potential adverse health
      impacts associated with their use. These range from cancer and cognitive
      deficiencies to subjective effects, such as a feeling of warmth around the ear
      used, headache and fatigue. We provide an overview of the concerns raised and
      summarise what is known about them. We conducted a literature search in
      Pubmed/Medline to identify published papers on health effects of mobile phones,
      and an intensive search on the Internet to collect data on the global use of
      mobile phones. In the year 2000, there were an estimated 500 million mobile phone
      users worldwide. Today, there are about 3.3 billion users. The use of mobile
      phones among young children and adolescents is also increasing. Health-risk
      research has mainly focused on adults and on a single outcome, brain tumours. No
      significant relationship has been established between mobile phone use and the
      incidence or growth of brain tumours. Other research indicates emerging concerns,
      including hearing problems and self-reported health symptoms, such as tiredness,
      stress, headache, anxiety, concentration difficulties and sleep disturbances, but
      results remain inconclusive. Currently, there is little epidemiological evidence
      indicating that the use of mobile phones causes adverse health effects.

PMID- 22460287
TI  - Population response to the risk of vector-borne diseases: lessons learned from
      socio-behavioural research during large-scale outbreaks.
AB  - Vector-borne infectious diseases, such as malaria, dengue, chikungunya, and West
      Nile fevers are increasingly identified as major global human health threats in
      developing and developed countries. The success or failure of vector control
      rests mainly on the nature and scale of the behavioural response of exposed
      populations. Large-scale adoption of recommended protective behaviour represents
      a critical challenge that cannot be addressed without a better understanding of
      how individuals perceive and react to the risk of infection. Recently, French
      overseas territories faced large-scale outbreaks: an epidemic of chikungunya
      fever in La Re' union and Mayotte (2005-2006) and four successive outbreaks of
      dengue fever in one Caribbean island, Martinique (1995-2007). To assess how these
      populations perceived and responded to the risk, and how the nature and scale of
      protection affected their clinical status, socio-epidemiological surveys were
      conducted on each island during the outbreaks. These surveys address three
      crucial and interconnected questions relevant to the period after persons
      infected by the virus were identified: which factors shape the risk of acquiring
      disease? Which socio- demographic characteristics and living conditions induce a
      higher likelihood of infection? What is the impact of risk perception on
      protective behaviours adopted against mosquito bites? Grounded on the results of
      these surveys, a general framework is proposed to help draw out the knowledge
      needed to reveal the factors associated with higher probability of infection as
      an outbreak emerges. The lessons learnt can inform health authorities' efforts to
      improve risk communication programmes, both in terms of the target and content of
      messages, so as to explore new strategies for ensuring sustainable protective
      behaviour. The authors compare three epidemics of vector-borne diseases to
      elucidate psychosocial factors that determine how populations perceive and
      respond to the risk of infectious disease.

PMID- 22460288
TI  - An assessment of bioterrorism competencies among health practitioners in
      Australia.
AB  - Public health and medical professionals are expected to be well prepared for
      emergencies, as they assume an integral role in any response. They need to be
      aware of planning issues, be able to identify their roles in emergency
      situations, and show functional competence. However, media perceptions and non
      empirical publications often lack an evidence base when addressing this topic.
      This study attempted to assess the competencies of various health professionals
      by obtaining quantitative data on the state of bioterrorism preparedness and
      response competencies in Australia using an extensive set of competencies
      developed by Kristine Gebbie from the Columbia University School of Nursing
      Center for Health Policy with funding from the US Centres for Disease Control and
      Prevention. These competencies reflect the knowledge, capabilities, and skills
      that are necessary for best practice in public health. Sufficient data were
      collected to enable comparison between public health leaders, communicable
      disease specialists, clinicians (with and without medical degrees), and
      environmental health professionals. All health professionals performed well.
      However, the primary finding of this study was that clinicians consistently self
      assessed themselves as lower in competence, and clinicians with medical degrees
      self-assessed themselves as the lowest in bioterrorism competence. This has
      important implications for health professional training, national benchmarks,
      standards, and competencies for the public health workforce.

PMID- 22460289
TI  - The public's acceptance of novel vaccines during a pandemic: a focus group study
      and its application to influenza H1N1.
AB  - As influenza H1N1 spreads around the world, health officials are considering the
      development and use of a new vaccine to protect the public and help control the
      outbreak. Acceptance of novel vaccines during health crises, however, is
      influenced by perceptions of a range of risks, including the risk of infection,
      risk of becoming severely ill or dying if infected, as well as the risk of
      serious side and long-term effects of the vaccine. A study on 11 focus groups was
      conducted with the public in Vancouver, Canada in 2006 and 2007 to explore how
      people assess these risks and how these assessments relate to their willingness
      to use novel vaccines in a pandemic. Concerns about using new vaccines during a
      pandemic differ from concerns about using established products in a non-crisis
      situation. Participants were hesitant to use novel vaccines because of a low
      perception of the early risk of infection in a pandemic, coupled with the many
      uncertainties that surround new vaccines and the emerging infectious disease, and
      owing to the concern that unsafe pharmaceuticals may be rushed to market during a
      health crisis. Understanding the public's assessment of the risks related to, and
      willingness to use, novel vaccines during a pandemic can help officials promote
      disease-control measures in ways that improve the likelihood of acceptance by the
      public and may increase uptake of an H1N1 vaccine.

PMID- 22460291
TI  - A debut for base stabilized monoalkylsilylenes.
AB  - The first base stabilized monoalkylsilylenes LSitBu (2) and LSi[C(SiMe(3))(3)]
      (3) (L = PhC(NtBu)(2)) were synthesized by the facile metathesis reactions of
      LitBu and KC(SiMe(3))(3) with LSiCl (1). The reaction of LSitBu (2) with N(2)O
      afforded the dimer [LSitBu(MU-O)](2) (4) which contains a four-membered Si(2)O(2)
      ring.

PMID- 22460290
TI  - Successful control of vancomycin-resistant Enterococcus faecium outbreak in a
      neurosurgical unit at non-endemic region.
AB  - Vancomycin-resistant enterococci (VRE) have emerged in many parts of the world,
      but have only been reported sporadically in Hong Kong. We report an outbreak of
      vancomycin-resistant Enterococcus faecium (VREfm) in a neurosurgical unit at a
      tertiary teaching hospital between 3 March and 3 April 2009 in Hong Kong. During
      the outbreak investigation, clinical samples from 193 (91.5%) of 211 patients who
      had stayed in the neurosurgical unit and 506 environmental samples were screened
      for VREfm. Besides the index case, another 3 (1.6%) out of 192 patients were
      found to be positive for VREfm. Two (0.4%) out of 506 environmental samples were
      positive for VREfm. All four clinical and two environmental isolates were found
      to be clonally related by pulse-field gel electrophoresis. The risk factors for
      nosocomial acquisition of VREfm included advanced age (P=0.047), presence of
      nasogastric tubing (P=0.002) and tracheostomy (P<0.001), and the use of beta
      lactam antibiotics (P<0.001) and vancomycin (P=0.001). Contrary to other VRE
      outbreaks in which the spread was rapid, the neurosurgical patients'
      immobilization because of coma and mechanical ventilation dependency, and the
      vigilant practice of hand hygiene by health-care workers successfully limited the
      number of secondary cases despite the delayed recognition of the index case. All
      patients with VREfm were labeled in the hospital network information system so
      that stringent infection control measures with contact precautions would be
      carried out once these patients were readmitted to prevent its spread in our
      locality.

PMID- 22460292
TI  - Regulation of interleukin-33 and thymic stromal lymphopoietin in human nasal
      fibroblasts by proinflammatory cytokines.
AB  - OBJECTIVES/HYPOTHESIS: Epithelial-derived interleukin (IL)-33 and thymic stromal
      lymphopoietin (TSLP) are critical regulators of innate and adaptive immune
      responses associated with Th2 cytokine-mediated inflammation, including allergic
      rhinitis. IL-33 and TSLP are expressed not only in epithelial cells but also
      fibroblasts, endothelial cells, and smooth muscle cells at nasal mucosal sites.
      However, the role and the regulation of IL-33 and TSLP in nasal fibroblasts
      remain unknown. We investigated the signal transduction regulation of IL-33 and
      TSLP induced by proinflammatory cytokines in nasal fibroblasts. STUDY DESIGN: In
      vitro, prospective study. METHODS: Nasal fibroblasts were derived from human
      nasal mucosa without allergic rhinitis. Expression of IL-33 and TSLP was examined
      in nasal fibroblasts treated with proinflammatory cytokines IL-1beta or tumor
      necrosis factor (TNF)-alpha after pretreatment with or without various inhibitors
      of signal transduction pathways. RESULTS: In nasal fibroblasts, both Western
      blotting and reverse transcriptase-polymerase chain reaction demonstrated that
      expression of mRNAs and proteins of IL-33 and TSLP was increased by treatment
      with IL-1beta or TNF-alpha. Immunostaining revealed that IL-33-positive nuclei
      were markedly increased by the treatment with IL-1beta or TNF-alpha. Enzyme
      linked immunosorbent assay showed that fibroblast-released TSLP was significantly
      increased by treatment with IL-1beta or TNF-alpha. The upregulation of both IL-33
      and TSLP proteins by treatment with IL-1beta was prevented by inhibitors of pan-
      protein kinase C (PKC), p38 mitogen-activated protein kinase, and nuclear factor
      (NF)-kappaB. In the cells treated with TNF-alpha, upregulation of IL-33 protein
      was prevented by inhibitors of phosphoinositide 3-kinase (PI3K), c-Jun N-terminal
      kinase (JNK), and NF-kappaB, whereas upregulation of TSLP protein was prevented
      by inhibitors of pan-PKC, PI3K, JNK, and NF-kappaB. CONCLUSIONS: Expression of IL
      33 and TSLP in nasal fibroblasts was regulated via distinct signal transduction
      pathways including NF-kappaB.

PMID- 22460293
TI  - Psychiatric manifestations in patients with dysautonomy associated with systemic
      lupus erythematosus.
AB  - The psychiatric manifestations of three patients with systemic lupus
      erythematosus (SLE) and neuropathic dysautonomic processes are described. All
      patients had a severe form of SLE with neurological, renal, articular, pulmonary
      or haematological manifestations. All three have two types of psychiatric
      manifestations: (1) a chronic and progressive depression and (2) a complex
      dissociative disorder during the acute episodes of postural hypotension. A
      provocative test with SPECT with 99mTc-HmPAO to be done during the episode of
      orthostatic hypotension may contribute to clinical assessment of complex changes
      in cerebral regional perfusion.

PMID- 22460294
TI  - Recurrent diffuse alveolar haemorrhage in a patient with systemic lupus
      erythematosus: long-term benefit of rituximab.
AB  - Diffuse alveolar haemorrhage (DAH) is an uncommon complication of systemic lupus
      erythematosus (SLE), and recurrences of DAH with remission periods are unusual.
      We describe a young woman with cachexia as the initial manifestation of SLE who
      presented posterior reversible encephalopathy syndrome (PRES), intestinal
      vasculitis and four episodes of DAH even though she was receiving combined immune
      suppressive therapy. After treatment with rituximab (RTX) the patient has not
      presented further episodes of DAH.

PMID- 22460295
TI  - The Frankfurt early intervention program FFIP for preschool aged children with
      autism spectrum disorder: a pilot study.
AB  - Different early intervention programs, developed predominantly in the US, for
      preschool aged children with autism spectrum disorders (ASD) have been published.
      Several systematic review articles including a German Health Technology
      Assessment on behavioural and skill-based early interventions in children with
      ASD reported insufficient evidence and a substantial problem of generalisability
      to the German context. In Germany, approx. 2-5 h early intervention is supported
      by social services. Here, we report the results of a 1 year pre-post pilot study
      on a developmentally based social pragmatic approach, the Frankfurt Early
      Intervention program FFIP. In FFIP, individual 2:1, behaviourally and
      developmentally based therapy with the child is combined with parent training and
      training of kindergarten teachers. Treatment frequency is 2 h/week. Outcome
      measures were the Vineland Adaptive Behaviour Scales II (VABS), mental age and
      the ADOS severity score. Improvements after 1 year were observed for the VABS
      socialisation scale and the mental age quotient/IQ (medium effect sizes). Results
      are comparable with several other studies with a similar or slightly higher
      therapeutic intensity implementing comparable or different early intervention
      methods or programs. Compared to most high-intensity programs (30-40 h/week),
      lower cognitive gains were observed. Results have to be replicated and assessed
      by a randomized-controlled study before any final conclusions can be drawn.

PMID- 22460296
TI  - Cerebrospinal fluid beta-amyloid 1-42 correlates with rate of progression in
      Alzheimer's disease.
AB  - Emerging treatment options targeting the pathogenetic mechanisms in Alzheimer's
      disease (AD) and the need to monitor efficacy during treatment trials necessitate
      the use of biomarkers, which not only may facilitate early and reliable
      diagnosis, but may also assist in the stratification of patient populations
      according to their rate of progression. The objective of the present study is to
      examine whether demographic and cerebrospinal fluid (CSF) parameters at initial
      evaluation [total tau, tau phosphorylated at threonine-181 and amyloid-beta(1-42)
      (Abeta42)] can be used to discriminate between slow and rapid progressors in
      patients with AD. A total of 74 AD patients were included in the study. Patients
      recruited were divided into slow and rapid progressors according to their Mini
      Mental Status Examination (MMSE) score decline before evaluation. Patients with a
      drop rate of >4/year were considered rapid progressors. Commercially available
      ELISA kits were used for measuring CSF biomarkers. Comparisons were performed
      using analysis of covariance. Significantly lower Abeta42 levels in the CSF were
      found in rapid (mean 392 pg/ml) as compared to slow progressors (mean 453 pg/ml),
      with a p value of 0.042. The results of the present study suggest that levels of
      the Abeta42 peptide may be related to the rate of disease progression. Further
      studies with a prospective design are needed in order to test the possible
      predictive value of CSF Abeta42 analysis.

PMID- 22460297
TI  - Methylphenidate (MPH) promotes visual cortical activation in healthy adults in a
      cued visuomotor task.
AB  - Seeking for the mechanisms by which methylphenidate (MPH) improves behavior has
      demonstrated that MPH modulates excitability in the primary motor cortex.
      However, little is known about the influence of MPH on top-down controlled
      mechanisms in the sensory domain. The present study explored the effects of MPH
      on the activation of visual cortices in healthy adults who performed a cued visuo
      motor task in a double-blind placebo-controlled crossover design. Two distinct
      measures, posterior alpha power and occipital slow cortical potentials (SCPs),
      were used to reflect raise in excitability and attention-based activation of
      visual cortical areas. According to the results, performance parameters (reaction
      time, response variance and error rate) were not affected by MPH. At the
      neurophysiologic level reflected by reduced alpha power, MPH increased the
      overall excitability of the occipital cortex, but not the parietal cortex. Before
      the cued response, MPH reduced alpha power and increased SCPs only before right
      hand responses, mostly at the right occipital location. It can be concluded that
      in visuo-motor tasks, MPH has the potency of adjusting the background
      excitation/inhibition balance of visual areas. Additionally, MPH may raise the
      attention controlled activation of visual cortical regions, especially during
      increased response control.

PMID- 22460298
TI  - Family matters: examining a multi-family group intervention for women with BRCA
      mutations in the scope of genetic counselling.
AB  - The availability of family-centred services for women genetically at-risk for
      breast and ovarian cancer (BRCA) due to deleterious genetic mutations is still
      scarce, despite the distress that these women and their families may experience.
      This study describes a multi-family group intervention for women who tested
      positive for BRCA mutations and their families. Methods include a time-limited
      psycho-educational programme involving educational and support components and
      consisting of four semi-structured multi-family sessions. Three families (a total
      of nine people) attended the programme in genetic counselling for hereditary
      cancers at a Portuguese public hospital. A focus group interview was performed 1
      month after the last session to assess both the practical and the psychosocial
      impacts and to collect suggestions from participants. The present paper focuses
      on the practical aspects of the intervention, its development and its evaluation.
      Participants reported that the programme is well-structured and that responds to
      the needs of patients and their families by improving coping skills and medical
      awareness in the adaptation to genetic illness. Results reinforce the need to
      integrate psychosocial and family-oriented interventions in genetic counselling,
      addressing the holistic experience of hereditary disease. Recommendations for
      enhancing the services available are provided. The multi-family discussion group,
      combining educative and supportive services with a family focus, can be
      successfully adapted in genetic counselling protocols.

PMID- 22460299
TI  - Using a community of practice to develop standards of practice and education for
      genetic counsellors in Europe.
AB  - The profession of genetic counselling is developing in Europe in response to the
      increased need for genetic healthcare. Standards of education and professional
      practice are needed to ensure that patients are provided with genetic counselling
      of an appropriate quality. However, such standards need to be relevant to
      practitioners in many different national and healthcare settings. In order to
      develop appropriate standards and a code of practice to guide professionals in
      Europe, we formed a community of practice that includes genetic nurses and
      counsellors, plus other interested health professionals, from 23 European
      countries. With reference to the European core competences for genetic
      counsellors, the members of the network developed a set of professional standards
      for practice, educational standards and a code of practice. It is strongly
      suggested that the title genetic counsellor should become a protected title in
      Europe and that practitioners are educated via a master level degree in genetic
      counselling. These standards have been approved by the members of the network and
      the existing professional national societies for genetic nurses and counsellors.
      They provide a foundation for building the profession of genetic counselling in
      Europe and for provision of equitable care across European countries. Further
      work is now needed to ensure that appropriate educational opportunities exist to
      train practitioners and that clinical teams utilise the expertise of these
      professionals appropriately to enhance the care offered to families at risk of or
      affected by genetic conditions.

PMID- 22460300
TI  - Development of a questionnaire for evaluating genetics education in general
      practice.
AB  - To support developments in genetics education, we constructed the GPGeneQ
      questionnaire to assess skills required for the practice of genetics by general
      practitioners (GPs). We describe the process of developing and validating this
      questionnaire to provide a detailed guide in the construction for questionnaires
      in the application of evaluating genetics education. The GPGeneQ was developed
      through a multi-step process with the initial draft based on a theoretical
      framework and literature review. The subsequent draft instrument contained three
      scales pertaining to GPs' knowledge, self-reported behaviour and attitudes
      regarding genetics in medicine. Content and ecological validity were measured by
      an iterative Delphi process involving experts, GPs and consumers of health
      services. Piloting to assess construct and criterion validity was conducted with
      a sample of GPs attending an educational workshop that was presented on a number
      of separate occasions in Victoria, Australia. Results from evaluations of 145 GPs
      participating in ten workshops revealed evidence for validity and reliability of
      the GPGeneQ: knowledge change (p < 0.001; CI, -1.63 to -0.68), behaviour change
      (p < 0.001; CI, -4.15 to -2.21), attitudinal change (p = 0.002; CI, -2.68 to 
      0.62). This paper details the procedures involved in developing and validating an
      assessment questionnaire for genetics education. The GPGeneQ is the first
      validated questionnaire covering a broad range of topics that is designed to
      provide a reliable measure for the evaluation of genetics education specifically
      in general practice. The procedures used are transferable to the construction of
      any instrument for use in genetics or other medical education.

PMID- 22460303
TI  - Erratum: A reply to community genetics: 1998-2009... and beyond.

PMID- 22460302
TI  - A reply to community genetics: 1998-2009... and beyond.

PMID- 22460301
TI  - Points to consider in assessing and appraising predictive genetic tests.
AB  - The use of predictive genetic tests is expanding rapidly. Given limited health
      care budgets and few national coverage decisions specifically for genetic tests,
      evidence of benefits and harms is a key requirement in decision making; however,
      assessing the benefits and harms of genetic tests raises a number of challenging
      issues. Frequently, evidence of medical benefits and harms is limited due to
      practical and ethical limitations of conducting meaningful clinical trials. Also,
      clinical endpoints frequently do not capture the benefit appropriately because
      the main purpose of many genetic tests is personal utility of knowing the test
      results, and costs of the tests and counseling can be insufficient indicators of
      the total costs of care. This study provides an overview of points to consider
      for the assessment of benefits and harms from genetic tests in an ethically and
      economically reflected manner. We discuss whether genetic tests are sufficiently
      exceptional to warrant exceptional methods for assessment and appraisal.

PMID- 22460304
TI  - Assimilation of elements and digestion in grass shrimp pre-exposed to dietary
      mercury.
AB  - Grass shrimp Palaemonetes pugio were fed mercury (Hg)-contaminated oligochaetes
      for 15 days and analyzed for Hg, cadmium (Cd), and carbon assimilation
      efficiencies (AE) as well as toxicological end points related to digestion.
      Disproportionate increases in stable Hg concentrations in shrimp did not appear
      to be related to partitioning to trophically available Hg in worms. Hg AE by pre
      exposed shrimp reached a plateau (approximately 53 %), whereas Cd AE varied
      (approximately 40-60 %) in a manner that was not dose-dependent. Carbon AE did
      not differ among treatments (approximately 69 %). Gut residence time was not
      impacted significantly by Hg pre-exposure (grand median approximately 465 min),
      however, there was a trend between curves showing percentages of individuals with
      markers in feces over time versus treatment. Feces-elimination rate did not vary
      with dietary pre-exposure. Extracellular protease activity varied approximately
      1.9-fold but did not exhibit dose-dependency. pH increased over the range of Hg
      pre-exposures within the anterior (pH approximately 5.33-6.51) and posterior (pH
      approximately 5.29-6.25) regions of the cardiac proventriculus and Hg
      assimilation exhibited a negative relationship to hydrogen ion concentrations.
      The results of this study indicate that previous Hg ingestion can elicit post
      assimilatory impacts on grass shrimp digestive physiology, which may, in turn,
      influence Hg assimilation during subsequent digestive cycles.

PMID- 22460305
TI  - Can neutrophil-to-lymphocyte ratio predict the survival of colorectal cancer
      patients who have received curative surgery electively?
AB  - PURPOSE: We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) on
      disease-free survival in patients with stages I to III colorectal cancer (CRC).
      METHODS: There were 3857 patients identified from our database. We used receiver
      operating characteristic (ROC) analysis to identify the best cutoff value of NLR.
      A 5-year disease-free survival was used as end point. Survival analysis was used
      to assess the NLR effect, after stratification by several clinopathologic
      factors. RESULTS: In the ROC analysis, NLR = 3 had the highest sensitivity and
      specificity. Elevated NLR (>3) in colon cancer seemed to accompany larger tumor
      size (~5 cm) and more advanced T stage. By multivariate analysis, elevated NLR in
      colon cancer was associated with an increased risk of disease progression or
      cancer death [hazard ratio (HR) 1.377, 95  % confidence interval 1.104-1.717, P =
      0.014]. However, elevated NLR in rectal cancer lost its significance in
      multivariate analysis (HR 1.121, 95  % confidence interval 0.941-1.336, P =
      0.200). Patients with elevated NLR had worse outcome, especially for colon
      cancer. CONCLUSIONS: Preoperative NLR influenced the disease-free survival in
      patients with stages I to III CRC. Elevated NLR (>3) was associated with worse
      outcome (5-year disease-free survival 66.3  % vs. 78.9  % in colon cancer, P <
      0.001; 60. 5 % vs. 66.2  % in rectal cancer, P = 0.008). The difference was
      larger in colon cancer than in rectal cancer. NLR should be considered as a
      prognostic factor for stages I to III CRC patients after curative surgery.

PMID- 22460306
TI  - Cap-assisted colonoscopy versus conventional colonoscopy: systematic review and
      meta-analysis.

PMID- 22460307
TI  - Evaluation of the coefficient of thermal expansion of human and bovine dentin by
      thermomechanical analysis.
AB  - The mismatch of thermal expansion and contraction between restorative materials
      and tooth may cause stresses at their interface, which may lead to microleakage.
      The present work compared the coefficient of thermal expansion (CTE) with the
      thermomechanical behavior of human and bovine teeth and determined if the CTE is
      a suitable parameter to describe tooth behavior. Fifteen human third molar and 15
      bovine incisor tooth slices (6*5*2 mm) were allocated to 3 groups according to
      the test environment: G1 - room condition, G2 - 100% humidity, G3 - desiccated
      and tested in dry condition. Each specimen was weighed, heated from 20 to 70oC at
      10oC min-1 and reweighed. The CTE was measured between 20 and 50oC. Fresh dentin
      (human -0.49% +/- 0.27, bovine -0.22% +/- 0.16) contracted on heating under dry
      condition. Under wet conditions, only human teeth (-0.05% +/- 0.04) showed
      contraction (bovine 0.00% +/- 0.03) accompanied by a significantly lower (p<0.05)
      weight loss than in dry specimens (human 0.35% +/- 0.15, bovine 0.45% +/- 0.20).
      The desiccated dentin expanded on heating without obvious weight changes (0.00%
      +/- 0.00). The CTE found was, respectively, in dry, wet and dissected conditions
      in oC(-1): human (-66.03*10(-6), -6.82*10(-6), 5.52*10(-6)) and bovine (
      33.71*10(-6), 5.47*10(-6), 4.31*10(-6)). According to its wet condition, the
      dentin showed different CTEs. The thermal expansion behavior of human and bovine
      dentin was similar. A simple evaluation of the thermal expansion behavior of
      tooth structure by its CTE value may not be appropriate as a meaningful
      consideration of the effects on the tooth-material interface.

PMID- 22460308
TI  - Bond strength between fiber posts and composite resin core: influence of
      temperature on silane coupling agents.
AB  - This study evaluated the effect of air drying temperature and different silane
      coupling agents on the bond strength between glass fiber posts and composite
      resin core. The post surface was cleaned with alcohol and treated with different
      silane coupling agents, being three prehydrolyzed silanes [Silano (Angelus),
      Prosil (FGM), RelyX Ceramic Primer (3M ESPE)] and one two-component silane
      [Silane Coupling Agent (Dentsply)]. Two post-silanization air drying
      temperatures, 23oC and 60oC, were applied. A cylindrical plastic matrix was
      placed around the silanized post and filled with composite resin. Each bonded
      post provided 7 slices for push-out testing. Each slice was loaded to failure
      under compression at a cross-head speed of 0.5 mm/min. Data were analyzed by two
      way ANOVA and Scott-Knott tests (alpha=0.05). Dunnett's test was used to compare
      the mean of the control group with that of each experimental group. Scanning
      electron microscopy (SEM) was used to evaluate the interface of the fractured
      slices. For the 23oC air drying temperature, the use of RelyX Ceramic Primer
      resulted in significantly lower bond strength than the other silane coupling
      agents, while the bond strength with Silane Coupling Agent was the highest of all
      groups. Only with Silane Coupling Agent, the bond strength for the 23oC air
      drying temperature was significantly higher than that for 60oC air drying. In
      conclusion, the use of warm air drying after silane application produced no
      increase in the bond strength between the fiber-reinforced composite post and the
      composite core. The two-component silane produced higher bond strength than all
      prehydrolyzed silanes when it was used with air drying at room temperature.

PMID- 22460309
TI  - Effect of experimental Ricinus communis solution for denture cleaning on the
      properties of acrylic resin teeth.
AB  - This study evaluated Knoop hardness, surface roughness and color alteration of
      artificial teeth for dentures after immersion in water, 1% sodium hypochlorite
      and an experimental solution of 2% Ricinus communis (RC). Thirty specimens of
      Vipi, Biolux and Trilux were analyzed. Tests of Knoop hardness, surface roughness
      and color alteration were conducted immediately after specimen preparation (T0)
      and after two immersion protocols for 15 days (DeltaT(15)) and 183 days
      (DeltaT(183)). Data variation (DeltaT) were subjected to ANOVA and Tukey's test
      (p<0.05). At DeltaT(15), Vipi presented hardness increase and Biolux presented
      the highest variation (p=0.01). RC caused the highest increase in hardness (p=0)
      and the lowest increase (p=0.005) in roughness. Biolux presented the lowest color
      alteration (p =0). At DeltaT(183), Trilux underwent the highest hardness
      variation (p=0). Biolux presented an increase in roughness (p=0). There was no
      significant differences in color alteration among the artificial teeth (p=0.06)
      and among solutions (p=0.08) after 183 days of immersion. All solutions
      (distilled water, 1% sodium hypochlorite and 2% RC) caused alterations on the
      analyzed properties. Both immersion protocols caused alterations on the analyzed
      properties.

PMID- 22460310
TI  - Antioxidant activity by DPPH assay of potential solutions to be applied on
      bleached teeth.
AB  - The aim of this study was to assess, using the DPPH assay, the antioxidant
      activity of several substances that could be proposed to immediately revert the
      problems caused by bleaching procedures. The percentage of antioxidant activity
      (AA%) of 10% ascorbic acid solution (AAcidS), 10% ascorbic acid gel (AAcidG), 10%
      sodium ascorbate solution (SodAsS), 10% sodium ascorbate gel (SodAsG), 10% sodium
      bicarbonate (Bicarb), Neutralize((r)) (NE), Desensibilize((r)) (DES), catalase C
      40 at 10 mg/mL (CAT), 10% alcohol solution of alpha-tocopherol (VitE),
      Listerine((r)) (LIS), 0.12% chlorhexidine (CHX), Croton Lechleri (CL), 10 %
      aqueous solution of Uncaria Tomentosa (UT), artificial saliva (ArtS) and 0.05%
      sodium fluoride (NaF) was assessed in triplicate by 2,2-diphenyl-1-picryl
      hydrazyl-hydrate (DPPH) free radical assay. All substances exhibited antioxidant
      activity, except for CL. AAcidS, AAcidG and VitE exhibited the highest AA%
      (p<0.05). On the contrary, CHX, NE, LIS and NaF showed the lowest AA% (p<0.05).
      In conclusion, AAcidS, AAcidG, SodAsS, SodAsG and VitE presented the highest
      antioxidant activity among substances tested in this study. The DPPH assay
      provides an easy and rapid way to evaluate potential antioxidants.

PMID- 22460311
TI  - Effect of high-concentrated bleaching agents on the bond strength at dentin/resin
      interface and flexural strength of dentin.
AB  - This study evaluated the effect of bleaching agents on bond strength at the
      dentin/resin interface and the flexural strength of dentin. Forty maxillary
      canines were selected for the study. In the shear strength test, 40 slabs of
      intracoronary dentin (5 x 5 mm) obtained from buccal surfaces of the crowns were
      included in acrylic resin. In the flexural strength test, 40 dentin bars (8 x 2 x
      2 mm) were obtained from the roots. The 40 hemi-sections of the lingual surface
      were prepared for scanning electron microscopy (SEM). The specimens were divided
      into 4 groups according to the bleaching protocol (n=10): Unbleached (control),
      Sodium perborate + 20% hydrogen peroxide (SP + 20% HP), 37% carbamide peroxide
      (37% CP) and 38% hydrogen peroxide (38% HP). After 7 days, the bond strength
      specimens were restored and tested. Dentin bars were bleached and subjected to a
      three-point bending test. Data (MPa) were analyzed by ANOVA and Tukey's test
      (alpha=0.05). In the shear test, the control group was superior (p<0.05) to the
      bleached groups, which, in turn, were statistically similar (p>0.05). In the
      flexural strength test, the control group also had the highest values and
      differed significantly from the other groups (p<0.05). SEM revealed smear layer
      in all groups, with fissures in the bleached specimens. SP + 20% HP and 38% HP
      showed discontinuous interfaces with few tags. In conclusion, bond strength of
      restorative material to dentin and flexural strength of dentin were reduced after
      the use of high-concentration bleaching agents.

PMID- 22460312
TI  - Bacteriostatic effect of copaiba oil (Copaifera officinalis) against
      Streptococcus mutans.
AB  - This study evaluated the inhibitory activity of copaiba oil (Copaifera
      officinalis against the cariogenic microorganism, Streptococcus mutans. For such
      purpose, a minimum inhibition concentration test of copaiba oil against S. mutans
      was performed, using the serial dilution in broth technique, with a negative
      control, a positive control (0.12% chlorhexidine) and a 10% copaiba oil solution
      as a test. A minimum bactericidal concentration test with tubes presenting
      microbial inhibition was also conduced. In the minimum inhibitory concentration
      test, copaiba oil showed inhibition of bacterial growth at all concentrations
      tested up to 0.78 uL/mL of the 10% copaiba oil solution in the broth. In
      addition, the negative control had no inhibition, and the 0.12% chlorhexidine
      solution was effective up to 6.25 uL/mL in the broth. Copaiba oil showed a
      bacteriostatic activity against S. mutans at low concentrations, and could be a
      an option of phytotherapic agent to be used against cariogenic bacteria in the
      prevention of caries disease.

PMID- 22460313
TI  - Cytotoxicity of bovine and porcine collagen membranes in mononuclear cells.
AB  - This study compared the cytotoxicity and the release of nitric oxide induced by
      collagen membranes in human mononuclear cells. Peripheral blood was collected
      from each patient and the separation of mononuclear cells was performed by
      Ficoll. Then, 2x10(5) cells were plated in 48-well culture plates under the
      membranes in triplicate. The polystyrene surface was used as negative control.
      Cell viability was assessed by measuring mitochondrial activity (MTT) at 4, 12
      and 24 h, with dosage levels of nitrite by the Griess method for the same
      periods. Data had non-normal distribution and were analyzed by the Kruskal-Wallis
      test (p<0.05). Statistically significant differences (p<0.05) were observed
      between the membranes and the control in the experimental period, although there
      was a significant reduction in viability over time (p<0.01). At 4 and 12 h, the
      porcine membrane induced a higher release of nitrite compared with the control
      and bovine membrane, respectively (p<0.01), and this difference was maintained at
      24 h (p<0.05). This in vitro study showed that the porcine collagen membrane
      induces an increased production of proinflammatory mediators by mononuclear cells
      in the first hours of contact, decreasing with time.

PMID- 22460314
TI  - Fluoride concentration in the top-selling Brazilian toothpastes purchased at
      different regions.
AB  - To be relevant in terms of public health, widely-used toothpastes should have at
      least 1,000 ppm of soluble fluoride (F) concentration. Thus, the concentrations
      of total fluoride (TF) and total soluble fluoride (TSF) in the top-selling
      Brazilian toothpastes were evaluated. Samples (n=3) from toothpastes Colgate Anti
      caries((r)), Colgate Total 12 Clean Mint((r)), Colgate Tripla Acao Menta
      Original((r)), Colgate Tripla Acao Menta Suave((r)) and Sorriso Dentes
      Brancos((r)) were obtained from each of the five regions of the country. The
      concentrations of TF and TSF were analyzed with ion-specific electrode calibrated
      with F standards and the results were expressed in ppm (ug F/g). All toothpastes
      showed TF concentration lower than 1,500 ppm F (1,388.2 +/- 25.8 to 1,483.2 +/-
      98.2). The TSF values were higher than 1,000 ppm F and ranged from 1,035.5 +/-
      61.5 to 1,221.8 +/- 35.2 for calcium carbonate/monofluorophosphate-based
      toothpastes and from 1,455.6 +/- 12.5 to 1,543.0 +/- 147.3 for silica/sodium
      fluoride-based toothpaste. Top-selling Brazilian toothpastes presented available
      fluoride concentration to control caries regardless of the region where they are
      purchased.

PMID- 22460315
TI  - Comparison of different ultrasonic vibration modes for post removal.
AB  - This in vitro study compared different ultrasonic vibration modes for
      intraradicular cast post removal. The crowns of 24 maxillary canines were
      removed, the roots were embedded in acrylic resin blocks, and the canals were
      treated endodontically. The post holes were prepared and root canal impressions
      were taken with self-cured resin acrylic. After casting, the posts were cemented
      with zinc phosphate cement. The samples were randomly distributed into 3 groups
      (n=8): G1: no ultrasonic vibration (control); G2: tip of the ultrasonic device
      positioned perpendicularly to core surface and close to the incisal edge; and G3:
      tip of the ultrasonic device positioned perpendicularly to core surface at
      cervical region, close to the line of cementation. An Enac OE-5 ultrasound unit
      with an ST-09 tip was used. All samples were submitted to the tensile test using
      an universal testing machine at a crosshead speed of 1 mm/min. Data were
      subjected to one-way ANOVA and Tukey's post-hoc tests (alpha=0.05). Mean values
      of the load to dislodge the posts (MPa) were: G1 = 4.6 (+/- 1.4) A; G2 = 2.8 (+/-
      0.9) B, and G3= 0.9 (+/- 0.3) C. Therefore, the ultrasonic vibration applied with
      the tip of device close to the core's cervical area showed higher ability to
      reduce the retention of cast post to root canal.

PMID- 22460316
TI  - An in vivo radiographic evaluation of the accuracy of Apex and iPex electronic
      Apex locators.
AB  - The aim of this study was to evaluate in vivo the clinical applicability of two
      electronic apex locators (EALs) - Apex (Septodont) and iPex (NSK) - in different
      groups of human teeth by using radiography. The working lengths (WLs) of 100 root
      canals were determined electronically. The EAL to be used first was chosen
      randomly and a K-file was inserted into the root canal until the EAL display
      indicated the location of the apical constriction (0 mm). The K-file was fixed to
      the tooth and a periapical radiograph was taken using a radiographic film holder.
      The K-file was removed and the WL was measured. The same procedure was repeated
      using the other EAL. Radiographs were examined with the aid of a light-box with
      lens of *4 magnification by two blinded experienced endodontists. The distance
      between the file tip and the root apex was recorded as follows: (A) +1 to 0 mm,
      (B) -0.1 to 0.5 mm, (C) -0.6 to 1 mm, (D) -1.1 to 1.5 mm, and (E) -1.6 mm or
      greater. For statistical purposes, these scores were divided into 2 subgroups
      according to the radiographic apex: acceptable (B, C, and D) and non-acceptable
      (A and E). Statistically significant differences were not found between the
      results of Apex and iPex in terms of acceptable and non-acceptable measurements
      (p>0.05) or in terms of the distance recorded from file tip and the radiographic
      apex (p>0.05). Apex and iPex EALs provided reliable measurements for WL
      determination for endodontic therapy.

PMID- 22460317
TI  - Treatment of gingival recessions in heavy smokers using two surgical techniques:
      a controlled clinical trial.
AB  - Smokers have small root coverage which is associated with bad vascularity of
      periodontal tissues. This study evaluated a technique that can increase the blood
      supply to the periodontal tissues compared with a traditional technique. Twenty
      heavy smokers (10 males and 10 females) with two bilateral Miller class I
      gingival recessions received coronally positioned flaps in one side (Control
      group)and extended flap technique in the other side (Test group). Clinical
      measurements (probing pocket depth, clinical attachment level, bleeding on
      probing, gingival recession height, gingival recession width, amount of
      keratinized tissue, and width and height of the papillae adjacent to the
      recession) were determined at baseline, 3 and 6 months postoperatively. Salivary
      cotinina samples were taken as an indicator of the nicotine exposure level. No
      statistically significant differences (p>0.05) were detected for the clinical
      measurements or smoke exposure. Both techniques promoted low root coverage
      (Control group: 43.18% and Test group: 44.52%). In conclusion, no difference was
      found in root coverage between the techniques. Root coverage is possible and
      uneventful even, if rather low, in heavy smoker patients with low plaque and
      bleeding indices.

PMID- 22460318
TI  - Serotonin transporter gene polymorphisms: a case-control study.
AB  - Considerable evidence indicates that serotonergic mechanisms, particularly the
      serotonin transporter, are involved in alcoholism and tobacco use and are
      influenced by polymorphism of the promoter region of 5HTT (5-HTTLPR). As alcohol
      and tobacco consumption have been implicated in the pathogenesis of oral cancer,
      the purpose of this study was to investigate 5-HTTLPR polymorphism in patients
      with oral squamous cell carcinoma (OSCC) compared with a control group in a
      sample of Brazilian patients. One hundred and three patients affected by OSCC and
      103 volunteers without OSCC were genotyped for 5-HTTLPR. Both groups were matched
      for age, sex and tobacco use. The chi-squared test was used for statistical
      analysis (alpha=0.05). There was no statistically significant difference in 5
      HTTLPR genotypes between case and control group (p= 0.408). In conclusion, the
      present investigation demonstrated that serotonin transporter polymorphisms are
      not implicated in the OSSC development.

PMID- 22460319
TI  - Occurrence of traumatic dental injury in cases of domestic violence.
AB  - The purpose of this study was to investigate the prevalence and types of
      traumatic dental injuries in situations of domestic violence. A coross-sectional
      study was conducted and data were collected from the police occurrence records to
      domestic physical aggression between 2001 and 2005. Of the 1,844 subjects who
      underwent medical evaluation, 15 had information pertaining to traumatic dental
      injuries. From the medical records, the forensic medical reports completed by the
      forensic medical experts who examined the victims after the aggression were
      reviewed and data of individuals with dental injuries (e.g., fractures, luxation
      and avulsion) were collected. In the selected sample, there was a predominance of
      individuals with injuries to the head and neck region (38.7%), and the frequency
      of traumatic dental injuries among all injuries to the head and neck region was
      2.0%. The most frequently injured teeth were the maxillary incisors (31.8%),
      followed by the mandibular incisors (27.3%) and the maxillary canines (9.1%). In
      31.8% of the injured teeth, the forensic experts did not specify the
      nomenclature. Of the dental trauma cases, 59.1% were fractures, 27.2% were
      luxations and 13.7% were avulsions. In conclusion, domestic violence was an
      important etiologic factor of traumatic dental injury. The aggression in all
      cases occurred in the form of punches and slaps. Fracture was the most common
      type of traumatic dental injury, and the most frequently injured teeth were the
      incisors.

PMID- 22460320
TI  - Treatment of epulis fissuratum with carbon dioxide laser in a patient with
      antithrombotic medication.
AB  - Epulis fissuratum is a pseudotumor growth located over the soft tissues of the
      vestibular sulcus caused by chronic irritation from poorly adapted dentures.
      Treatment indication for these lesions is surgical excision with appropriate
      prosthetic reconstruction. The hemostatic capacity of carbon dioxide (CO(2))
      laser is well described in the literature as a useful tool in oral surgery,
      especially in patients with clotting disorders. This paper presents a case of a
      72-year-old female patient referred to the 'Nossa Senhora da Conceicao de Valongo
      Hospital' at Porto, Portugal, with a massive growth of vestibular oral mucosa in
      the mandible and maxilla associated with ill-fitting dentures, suggestive of
      epulis fissuratum. The patient was taking antithrombotic medication. The lesions
      were excised with CO(2) laser, and no significant complications, such as
      hemorrhage, pain, swelling or infection, were recorded. Twenty days after
      surgery, both areas were completely reepithelizaded. Prosthetic rehabilitation
      and function were achieved with the fabrication of new maxillary and mandibular
      dentures. Follow-up 1 month and 1 year after treatment revealed the areas free of
      recurrence. The use of CO(2) lasers is currently the gold standard in the
      excision of this type of lesion, especially in patients with hemorrhagic
      diathesis or under antithrombotic therapy.

PMID- 22460321
TI  - Giant sialocele following facial trauma.
AB  - Injuries in the parotid and masseter region can cause serious impairment
      secondary to damage of important anatomical structures. Sialocele is observed as
      facial swelling associated with parotid duct rupture due to trauma. The aim of
      this paper is to report a case of a giant traumatic sialocele in the parotid
      gland, secondary to a knife lesion in a 40-year-old woman. Conservative measures
      could not promote clinical resolution and a surgical intervention for the
      placement of a vacuum drain was selected. Under local anesthesia, a small
      incision was performed adjacent to parotid duct papilla, followed by muscular
      divulsion and draining of significant amount of saliva. An active vacuum suction
      drain was placed for 15 days, aiming to form a new salivary duct. This technique
      was shown to be a safe, effective and low-cost option, leading to complete
      resolution and no recurrence after 28 months of follow up.

PMID- 22460322
TI  - Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet
      formation.
AB  - A characteristic of apoptosis is the rapid accumulation of cytoplasmic lipid
      droplets, which are composed largely of neutral lipids. The proton signals from
      these lipids have been used for the non-invasive detection of cell death using
      magnetic resonance spectroscopy. We show here that despite an apoptosis-induced
      decrease in the levels and activities of enzymes involved in lipogenesis, which
      occurs downstream of p53 activation and inhibition of the mTOR signaling pathway,
      the increase in lipid accumulation is due to increased de novo lipid synthesis.
      This results from inhibition of mitochondrial fatty acid beta-oxidation, which
      coupled with an increase in acyl-CoA synthetase activity, diverts fatty acids
      away from oxidation and into lipid synthesis. The inhibition of fatty acid
      oxidation can be explained by a rapid rise in mitochondrial membrane potential
      and an attendant increase in the levels of reactive oxygen species.

PMID- 22460323
TI  - Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle
      cell disease.
AB  - Transcranial Doppler (TCD) ultrasonography helps to identify children with sickle
      cell disease (SCD) who are at an increased risk of stroke,making primary stroke
      prevention a reality. A cross-sectional study of145 Nigerian children aged >=3
      years with SCD was carried out to describe the pattern of cerebral blood flow
      (CBF) abnormalities. The mean time-averaged mean velocity (TAMV) was 152 +/-27.0
      cm/sec and122 +/-22.0 cm/sec in Hb SS and Hb S1C group, respectively. Abnormal
      velocities were recorded in six (4.7%) of the Hb SS patients and none of the Hb
      S1C while conditional risk (CR) velocities were recorded in 19.7% of Hb SS (low
      conditional 11.0%, high conditional 8.7%) and low conditional in 5.6% of Hb S1C
      cases. Cerebral flow velocities showed a negative correlation with age and
      hematocrit. Compared with African-American children, Nigerian children with Hb SS
      disease have a considerably higher prevalence of CR velocities.

PMID- 22460324
TI  - Aminoterminally truncated and oxidized amyloid-beta peptides in the cerebrospinal
      fluid of Alzheimer's disease patients.
AB  - Carboxyterminally elongated and aminoterminally truncated amyloid-beta (Abeta)
      peptides and their oxidized derivates are major constituents of human amyloid
      plaques. The objective of the present study was to clarify the diagnostic impact
      of the Abeta peptides 1-38ox, 2-40, and 2-42 peptides on the neurochemical
      cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD). For this
      purpose, 22 patients with AD and 20 non-demented disease controls (NDC) were
      comparatively analyzed for their cerebrospinal fluid pattern of Abeta1-38ox,
      Abeta2-40, and Abeta2-42 along with Abeta1-37, Abeta1-38, Abeta1-39, Abeta1-40,
      Abeta1-40ox, and Abeta1-42 using a novel sequential aminoterminally and
      carboxyterminally specific immunoprecipitation protocol and subsequent analysis
      in the Abeta-SDS-PAGE/immunoblot. The Abeta peptides 1-38ox, 2-40, and 2-42 could
      not be consistently detected in the investigated CSF samples, which applied to
      samples from AD and NDC patients alike. Otherwise, our approach revealed a
      striking decrease of Abeta1-42 and Abeta2-42, but not of Abeta1-38ox and Abeta2
      40 in AD. Both Abeta1-42 and Abeta2-42 reached reasonable accuracies for
      diagnosing AD alone as well as in relation to Abeta1-40, Abeta1-38, or the sum of
      all measured Abeta peptides. Abeta1-38ox was negatively correlated to the Mini
      Mental Status Examination score of AD patients, indicating that this peptide to
      linked to disease severity. We conclude that an exact analysis of CSF Abeta
      peptides regarding their carboxy- and aminoterminus as well as posttranslational
      modification may be a promising approach for diagnosing and tracking AD.

PMID- 22460325
TI  - Contribution of single photon emission computed tomography to the differential
      diagnosis of dementia in a memory clinic.
AB  - To evaluate the contribution of single photon emission computed tomography
      (SPECT) to the differential diagnosis of dementia, we studied 48 consecutive
      patients (median age: 63) with a degenerative or vascular dementia, a 99mTc-HMPAO
      SPECT imaging, and a diagnostic confirmation (autopsy or genetic mutation). The
      SPECT scans were visually rated by two nuclear medicine physicians (first blinded
      to the clinical data, then with the data). Comparisons between clinical diagnoses
      and/or SPECT imaging and neuropathology were performed. At the time of SPECT was
      performed, the clinical diagnosis of Alzheimer's disease (AD) sensitivity was
      83%, specificity was 76%, and diagnostic accuracy was 79%. The blinded SPECT
      sensitivity was 57%, specificity 92%, and diagnostic accuracy 75%. The SPECT
      associated with clinical data sensitivity was 65%, specificity 84%, and accuracy
      75%. The clinical diagnosis of frontotemporal-lobar degeneration (FTLD),
      progressive supranuclear palsy (PSP), and corticobasal degeneration syndrome
      (CBDs) sensitivity was 83%, specificity 87%, and accuracy 85%. The blinded SPECT
      sensitivity was 50%, specificity 97%, and accuracy 79%. The SPECT associated with
      clinical data sensitivity was 61%, specificity was 93%, and accuracy 81%.
      Whenever the blinded SPECT interpretation agreed with the clinical diagnosis of
      AD and FTLD/PSP/CBDs, the condition was confirmed by neuropathological assessment
      in all cases. Compared with clinical diagnosis alone, SPECT imaging improved the
      specificity of the etiological diagnosis in degenerative dementia, although its
      sensitivity was not as good as that of clinical diagnosis. For AD and
      FTLD/PSP/CBDs, agreement between the clinical and SPECT-based diagnoses was
      always confirmed by neuropathological assessment.

PMID- 22460326
TI  - Dynamic cerebral autoregulation in subjects with Alzheimer's disease, mild
      cognitive impairment, and controls: evidence for increased peripheral vascular
      resistance with possible predictive value.
AB  - Cerebrovascular dysfunction plays a role not only in vascular causes of cognitive
      impairment but also in Alzheimer's disease (AD). We hypothesized that cerebral
      autoregulation is impaired in patients with AD compared to subjects with mild
      cognitive impairment (MCI) and controls. Dynamic cerebral autoregulation (dCA)
      was investigated in 17 AD patients, 19 MCI subjects, and 20 controls (C). Groups
      were matched for age, gender, and level of education. Electrocardiogram and non
      invasive finger arterial blood pressure were measured and transcranial doppler
      ultrasonography was used to measure cerebral blood flow velocity in right and
      left middle cerebral artery (MCA). Cerebrovascular resistance index (CVRi) was
      also computed. dCA in supine position was quantified based on spontaneous blood
      pressure variations by computation of the linear transfer function between
      arterial blood pressure and MCA cerebral blood flow velocity. dCA gain and phase
      were evaluated for different frequency bands. Results were also evaluated using a
      3-parameter windkessel model (WKM). CVRi was significantly higher in AD (2.9 +/-
      0.2) compared to both MCI (2.3 +/- 0.1, p = 0.02) and C (2.1 +/- 0.1 mmHgs/cm, p
      = 0.002). Five MCI patients who converted to AD during the course of the study
      also had higher CVRi compared to non-converters (2.8 +/- 0.6 versus 2.1 +/- 0.5
      mmHgs/cm, p < 0.05). No significant differences in dCA gain and phase were found.
      In terms of the WKM approach, in the order C->MCI->AD groups showed about equal
      arterial resistance and peripheral compliance, but increased peripheral
      vasculature resistance (26 +/- 2 versus 36 +/- 3 mmHgs/ml in C resp. AD, p =
      0.004). In conclusion, AD patients compared to MCI patients and controls have
      increased CVRi, whereas dCA parameters do not seem to differentiate AD patients.
      For MCI patients, CVRi might have predictive value in developing AD.

PMID- 22460327
TI  - Multimodal imaging evidence for axonal and myelin deterioration in amnestic mild
      cognitive impairment.
AB  - White matter (WM) microstructural declines have been demonstrated in Alzheimer's
      disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM
      microstructural changes in aMCI after controlling for WM atrophy is unknown.
      Here, we address this issue through joint consideration of aMCI alterations in
      fractional anisotropy, mean diffusivity, axial diffusivity, and radial
      diffusivity, as well as macrostructural volume in WM and gray matter
      compartments. Participants were 18 individuals with aMCI and 24 healthy seniors.
      Voxelwise analyses of diffusion tensor imaging data was carried out using tract
      based spatial statistics (TBSS) and voxelwise analyses of high-resolution
      structural data was conducted using voxel based morphometry. After controlling
      for WM atrophy, the main pattern of TBSS findings indicated reduced fractional
      anisotropy with only small alterations in mean diffusivity/radial
      diffusivity/axial diffusivity. These WM microstructural declines bordered and/or
      were connected to gray matter structures showing volumetric declines. However,
      none of the potential relationships between WM integrity and volume in connected
      gray matter structures was significant, and adding fractional anisotropy
      information improved the classificatory accuracy of aMCI compared to the use of
      hippocampal atrophy alone. These results suggest that WM microstructural declines
      provide unique information not captured by atrophy measures that may aid the
      magnetic resonance imaging contribution to aMCI detection.

PMID- 22460328
TI  - Bip enhanced the association of GSK-3beta with tau during ER stress both in vivo
      and in vitro.
AB  - Hyperphosphorylated tau is the major component of intracellular neurofibrillary
      tangles, which is positively correlated with the cognitive decline in Alzheimer's
      disease (AD). The upstream factors leading to tau hyperphosphorylation are still
      not fully understood. Endoplasmic reticulum (ER) stress has been indicated in AD
      pathogenesis and the increased level of binding immunoglobulin protein (Bip), an
      important ER associated chaperon, is increased in AD brain. Here
      hyperphosphorylation of tau, activation of glycogen synthase kinase-3beta (GSK
      3beta), and elevation of Bip were induced by ventricular infusion of ER
      stressors, tunicamycin (TM) and thapsigargin (TG), in rats. GSK-3beta was found
      to be responsible for tau hyperphosphorylation induced by ER stressors both in
      vivo and in vitro. In addition, inhibited Akt, protein tyrosine phosphatase 1B,
      and activated Fyn were detected in vivo. Down-regulating Bip by tranfecting its
      siRNA plasmid significantly revised tau hyperphosphorylation in TG treated
      HEK293/tau cells, but the activation of GSK-3beta was still observed. By
      immunoprecipitation, we found that the binding levels of Bip to tau and GSK-3beta
      were significantly increased with the elevation of Bip in TM-treated rats.
      Moreover, in Bip overexpressed HEK293/tau cells, the binding levels of Bip to tau
      (mainly phosphorylated tau) and GSK-3beta were also significantly increased.
      However, beta-catenin, another important substrate of GSK-3beta, was not found
      bound to the increased Bip. All these data suggest an essential role of Bip in
      GSK-3beta dependent tau hyperphosphorylation in ER stress by promoting the
      binding of GSK-3beta to tau.

PMID- 22460329
TI  - Rapidly progressive Alzheimer's disease: a multicenter update.
AB  - The objective was to characterize a rapidly progressive subtype of Alzheimer's
      disease (rpAD). Multicenter (France, Germany, Japan, Spain) retrospective
      analyses of neuropathologically confirmed rpAD cases initially classified as
      prion disease due to their clinical phenotype were performed. Genetic properties,
      cerebrospinal fluid biomarkers, neuropathology, and clinical features were
      examined. Eighty-nine patients were included (median survival 10 months). APOE
      and PRNP codon 129 genotype distribution paralleled a healthy control group. APOE
      epsilon4 homozygosity was absent. Cerebrospinal fluid biomarkers were abnormal,
      but within a range as expected for classic AD, except for proteins 14-3-3, which
      were detectable in 42%. Thus, evidence of the existence of rpAD is accumulating.
      The APOE profile is intriguing, suggesting that this very rapid disease form
      might represent a distinct subtype of Alzheimer's disease.

PMID- 22460330
TI  - Relevance of in vivo neurophysiological biomarkers for mild cognitive impairment
      and Alzheimer's disease.
AB  - Visuospatial dysfunction including defects in motion perception in Alzheimer's
      disease (AD) and mild cognitive impairment (MCI) are clues to search for
      potential in vivo biomarkers. In this review, we focus on the clinical relevance
      of non-invasive neurophysiological findings in event-related potentials (ERPs)
      and functional magnetic resonance imaging (fMRI) to assess visual dysfunction in
      AD and MCI. We first summarize the current concept of the parallel visual
      pathways in primates and humans. Next, we outline the results of previous
      electrophysiological and fMRI studies on visual function in AD and MCI. Finally,
      we present the recent findings of our systematic ERP and fMRI approach to visual
      perception in AD and MCI. Our overview strongly indicates that visual impairments
      in patients with AD and MCI are mainly caused by dysfunction in higher-level
      parallel visual pathways. In particular, a deficit in ventro-dorsal stream
      function related to optic flow perception is responsible for the earliest and
      most prominent visual symptoms in MCI. Therefore, we conclude that ERP and fMRI
      measurements for visual perception can be used as in vivo biomarkers for early
      functional brain changes in MCI and AD patients.

PMID- 22460331
TI  - Efficient near-infrared in vivo imaging of amyoid-beta deposits in Alzheimer's
      disease mouse models.
AB  - The development of early diagnostic and prognostic tools for the visualization of
      amyloid-beta (Abeta) deposits is one important focus of current imaging research.
      In patients with Alzheimer's disease (AD), non-invasive and efficient detection
      of soluble and aggregated Abeta is important to determine the immediate success
      of intervention trails. The novel near infrared-fluorescence (NIRF) probe THK-265
      efficiently penetrates the blood-brain barrier and has a strong and efficient
      binding to cerebral Abeta. Ex vivo microscopy of i) THK-265-labeling of plaques
      in paraffin-embedded tissue and ii) cerebral cryo-sections after intravenous
      injection of THK-265 confirmed a systematic increase of the NIRF signal
      corresponding to Abeta plaque number and size during disease progression.
      Furthermore, we investigated different stages of plaque formation in amyloid-beta
      protein precursor transgenic mice in vivo after intravenous application of THK
      265 to evaluate different aggregation levels with NIRF signals. The intensity of
      the NIRF signal correlated well with the plaque burden, indicating its utility
      for direct monitoring of Abeta aggregation progression. In summary, our results
      support the use of the NIRF probe THK-265 for the diagnosis and direct
      visualization of amyloid deposits and open the possibility for efficient, pre
      symptomatic monitoring of Abeta deposition in the aging brain.

PMID- 22460333
TI  - Degraded mitochondrial DNA is a newly identified subtype of the damage associated
      molecular pattern (DAMP) family and possible trigger of neurodegeneration.
AB  - We previously showed a preferential degradation and down-regulation of
      mitochondrial DNA and RNA in hamster fibroblasts in response to hydrogen
      peroxide. Subsequent studies by others demonstrated that mitochondrial DNA can
      stimulate immune cells as a DAMP (damage associated molecular patterns) family
      member. However, the actual physical structure of this mitochondrial DNA DAMP and
      its importance in non-immune cell types are poorly understood. Here we report
      that transfected oxidant-initiated degraded mitochondrial polynucleotides, which
      we term "DeMPs", strongly induce the proinflammatory cytokines interleukin 6,
      monocyte chemotactic protein-1, and tumor necrosis factor alpha in mouse primary
      astrocytes. Additionally, proinflammatory IL1beta was induced, implicating DeMPs
      in inflammasome activation. Furthermore, human cerebrospinal fluid (CSF) and
      plasma were found to contain detectable DeMP signal. Finally, significant
      degradation of mitochondrial DNA was observed in response to either a bolus or
      steady state hydrogen peroxide. Combined, these studies demonstrate, all for the
      first time, that a pathophysiologically relevant form of mitochondrial DNA
      (degraded) can elicit a proinflammatory cytokine induction; that a brain cell
      type (astrocytes) elicits a proinflammatory cytokine induction in response to
      these DeMPs; that this induction includes the inflammasome; that astrocytes are
      capable of inflammasome activation by DeMPs; that DeMPs are detectable in CSF and
      plasma; and that hydrogen peroxide can stimulate an early stage cellular
      degradation of mitochondrial DNA. These results provide new insights and are
      supportive of our hypothesis that DeMPs are a newly identified trigger of
      neurodegenerative diseases such as Alzheimer's disease, which are known to be
      associated with early stage inflammation and oxidation.

PMID- 22460334
TI  - Urethral meatus deformities in girls as a factor in dysfunctional voiding.
AB  - PURPOSE: Girls with an anterior deflected urinary stream (ADUS) cannot void in
      the ideal toileting position, resulting in lower success rates of behavioral
      training programs. Purpose was to study prospectively the clinical effects of
      surgical meatus correction for ADUS in girls with dysfunctional voiding (DV).
      METHODS: A cohort of 171 DV patients aged 6-12 years was investigated. All had
      recurrent urinary tract infections (UTIs), staccato or interrupted uroflow, and
      >10% residual urine on ultrasound. For study purposes, all underwent a urodynamic
      study (UDS) to confirm DV. ADUS was recognized at first examination in 55
      patients (32%) and a dorsally directed meatal correction was performed to achieve
      a normal direction of the urinary stream. The non-ADUS group (116 girls) was
      given behavioral therapy (BT); however, a subgroup of 11 girls with ADUS was
      detected with persistent complaints after failed BT. These 11 girls also
      underwent a meatal correction. RESULTS: All DV complaints were resolved in 25 of
      the 55 (45%) girls from the original ADUS group and 8 of the 11 (73%) girls from
      the second group. During UDS, in the ADUS group free of complaints after meatal
      correction, a significantly higher P(max) (102 cmH(2) O) was found compared to
      those who did not benefit from correction (P(max) 76 cmH(2)O). CONCLUSION: In
      this study, 39% of female DV patients had ADUS complaints. After surgical
      correction, 50% were free of all complaints without requiring any further
      behavioral training. The fast recovery into a normal voiding pattern in these
      girls shows that a meatus deformity needs to be looked for in all girls
      presenting with DV.

PMID- 22460336
TI  - Acute stroke imaging: what is sufficient for triage to endovascular therapies?

PMID- 22460337
TI  - Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome.
AB  - HGPS is a rare syndrome of segmental premature aging. Our goal was to expand the
      scope of structural bone and soft-tissue craniofacial abnormalities in HGPS
      through CT or MR imaging. Using The Progeria Research Foundation Medical and
      Research Database, 98 imaging studies on 25 patients, birth to 14.1 years of age,
      were comprehensively reviewed. Eight newly identified abnormalities involving the
      calvaria, skull base, and soft tissues of the face and orbits were present with
      prevalences between 43% and 100%. These included J-shaped sellas, a mottled
      appearance and increased vascular markings of the calvaria, abnormally configured
      mandibular condyles, hypoplastic articular eminences, small zygomatic arches,
      prominent parotid glands, and optic nerve kinking. This expanded craniofacial
      characterization helps link disease features and improves our ability to evaluate
      how underlying genetic and cellular abnormalities culminate in a disease
      phenotype.

PMID- 22460338
TI  - Corticospinal tract MR signal-intensity pseudonormalization on magnetization
      transfer contrast imaging: a potential pitfall in the interpretation of the
      advanced compromise of upper motor neurons in amyotrophic lateral sclerosis.

PMID- 22460332
TI  - Structural brain alterations before mild cognitive impairment in ADNI: validation
      of volume loss in a predefined antero-temporal region.
AB  - Volume losses in the medial temporal lobe, posterior cingulated, and
      orbitofrontal region have been observed in Alzheimer's disease (AD). Smaller
      reductions in similar regions have also been reported in amnestic mild cognitive
      impairment (aMCI), a canonical precursor to AD. We previously demonstrated that
      volume loss in bilateral anteromedial temporal lobe is present at baseline in
      longitudinally followed normal subjects who later developed MCI or AD. In this
      study we compared grey matter volumes within this predefined anteromedial
      temporal region (AMTR) at baseline between: 1) normal subjects enrolled in the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) who subsequently developed
      cognitive complaints as reflected in a CDR memory box score of 0.5; and 2) normal
      subjects who remained normal over a median of 48 months of follow-up (CDR sum of
      boxes 0). We found significantly decreased volume within AMTR in the ADNI memory
      complainers. To relate AMTR results to those from conventional anatomy, we
      demonstrate that volumes extracted with the ICBM amygdala region had the best
      correspondence with AMTR volumes. In contrast, regions that have demonstrated
      volume loss in frank MCI and AD in ADNI, e.g., the posterior cingulate, did not
      show volume loss. These findings provide independent confirmation that volume
      changes preceding MCI occur in AMTR, a region of overlap between amygdala and
      anterior hippocampus.

PMID- 22460339
TI  - Recanalization of large intracranial vessels using the penumbra system: a single
      center experience.
AB  - BACKGROUND AND PURPOSE: The PS is an innovative mechanical device designed to
      recanalize large-vessel occlusions by thrombus aspiration. The purpose of this
      study was to evaluate the effectiveness and neurologic outcome of patients
      treated with the PS in the setting of acute ischemic stroke. MATERIALS AND
      METHODS: A total of 91 patients with acute ischemic stroke due to large-vessel
      occlusion were treated with the PS and were included in our retrospective study.
      In 14 patients, only the PS was used for treatment; in 77 patients, mechanical
      recanalization was combined with IA and/or IV thrombolysis. Outcome was measured
      by using the mRS; recanalization was assessed with the TICI score. RESULTS: Mean
      patient age was 62 +/- 19.4 years; the average NIHSS score at hospital admission
      was 17. Successful recanalization was achieved in 77% of patients. Median time
      from arterial puncture to recanalization was 49 minutes (quartiles, 31-86
      minutes). At follow-up, 36% of the patients showed an NIHSS improvement of >=10%,
      and 34% of the patients with an anterior circulation occlusion had an mRS score
      of <=2, whereas only 7% of the patients with a posterior occlusion had a
      favorable outcome at follow-up. In total, 20 patients died during
      hospitalization; none of these deaths were device-related. CONCLUSIONS: In this
      study, the PS was an effective device for mechanical recanalization. Successful
      recanalization with the PS was associated with significant improvement of
      functional outcome in patients experiencing ischemic stroke secondary to anterior
      circulation occlusions.

PMID- 22460340
TI  - The appearance of dural sealants under MR imaging.
AB  - Dural sealants are an adjunct to obtain watertight closure after intradural
      procedures. This study aims to characterize the appearance on MR imaging of 3
      commonly employed dural sealants: fibrin glue, PEGH, and BSAG. To this end,
      patients who underwent spinal intradural procedures that included the use of
      dural sealant during closure were identified retrospectively. Post-operative data
      on 15 patients, including complications such as pseudomeningocele formation and
      infection, were gathered. The appearance of dural sealants on follow-up MR
      imaging scans within 3 days of surgery was analyzed. Fifteen patients were
      identified (5 with fibrin glue, 5 with PEGH, and 5 with BSAG applied during
      closure) with appropriately timed post-operative MR imaging scans. All 3
      substances were identifiable based on anatomic location and imaging
      characteristics on post-operative MR imaging in standard T1, T1 PGFS, and T2 FSE.
      Definite differentiation between CSF and fibrin glue or PEGH was not possible
      with the T1 or T1 PGFS, or with the T2 FSE. Differences in intensity between CSF
      and BSAG were also not significant on either T1 sequence, but they were
      statistically significant on the T2 FSE. All patients had an uneventful post
      operative course, and no patients developed post-operative pseudomeningocele at
      30 days. This study concludes that water-based dural sealants such as fibrin glue
      and PEGH are difficult to differentiate from CSF on standard T1, T1 PGFS and T2
      FSE, while BSAG is easily recognized on the T2 FSE. Recognition of water-based
      sealants therefore requires communication between the neurosurgeon and the
      neuroradiologist to avoid post-operative misidentification.

PMID- 22460342
TI  - Postpublication errors in imaging-related journals.
AB  - BACKGROUND AND PURPOSE: Assessment of postpublication errors in peer-reviewed
      journals is difficult and the numbers and types are unknown. We reviewed
      published errata in major clinical imaging journals in an attempt to understand
      the numbers and sources of errors in published articles. MATERIALS AND METHODS:
      Five clinical imaging journals with the highest IFs were searched on-line using
      the terms "erratum" or "errata" anywhere in the title, abstract, or author
      listing for a total of 5 years. Each erratum was reviewed and categorized by type
      and source of responsibility. RESULTS: The following journals were assessed: JNM,
      Radiology, AJNR, AJR, and RadioGraphics. There were a total of 158 total errata
      and each was placed in 1 of the following categories: typographical (94), factual
      (6), image-related (48), statistical calculation (7), or serious foundational
      errors (3). Errata were also labeled as author (107) or journal responsibility
      (51). One hundred forty-eight errata were categorized as minor (typographical,
      factual, and image-related) and 10 as major (statistical calculation,
      foundational errors). CONCLUSIONS: Analysis of the 8910 articles published by the
      5 journals during the study period, revealed the number of minor and major errors
      were few, 1.66% and 0.11%, respectively. Of these errors, 93.7% were considered
      minor and 6.3% major. Most major errors were judged to be the responsibility of
      the authors, whereas most minor ones were the responsibility of the journals.

PMID- 22460341
TI  - The impact of lesion in-painting and registration methods on voxel-based
      morphometry in detecting regional cerebral gray matter atrophy in multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: VBM has been widely used to study GM atrophy in MS. MS
      lesions lead to segmentation and registration errors that may affect the
      reliability of VBM results. Improved segmentation and registration have been
      demonstrated by WM LI before segmentation. DARTEL appears to improve registration
      versus the USM. Our aim was to compare the performance of VBM-DARTEL versus VBM
      USM and the effect of LI in the regional analysis of GM atrophy in MS. MATERIALS
      AND METHODS: 3T T1 MR imaging scans were acquired from 26 patients with RRMS and
      28 age-matched NC. LI replaced WM lesions with normal-appearing WM intensities
      before image segmentation. VBM analysis was performed in SPM8 by using DARTEL and
      USM with and without LI, allowing the comparison of 4 VBM methods (DARTEL + LI,
      DARTEL - LI, USM + LI, and USM - LI). Accuracy of VBM was assessed by using NMI,
      CC, and a simulation analysis. RESULTS: Overall, DARTEL + LI yielded the most
      accurate GM maps among the 4 methods (highest NMI and CC, P < .001). DARTEL + LI
      showed significant GM loss in the bilateral thalami and caudate nuclei in
      patients with RRMS versus NC. The other 3 methods overestimated the number of
      regions of GM loss in RRMS versus NC. LI improved the accuracy of both VBM
      methods. Simulated data suggested the accuracy of the results provided from
      patient MR imaging analysis. CONCLUSIONS: We introduce a pipeline that shows
      promise in limiting segmentation and registration errors in VBM analysis in MS.

PMID- 22460343
TI  - Iron deposition on SWI-filtered phase in the subcortical deep gray matter of
      patients with clinically isolated syndrome may precede structure-specific
      atrophy.
AB  - BACKGROUND AND PURPOSE: Increasing evidence suggests that iron deposition is
      present in the later stages of MS. In this study we examined abnormal phase
      values, indicative of increased iron content on SWI-filtered phase images of the
      SDGM in CIS patients and HC. We also examined the association of abnormal phase
      with conventional MR imaging outcomes at first clinical onset. MATERIALS AND
      METHODS: Forty-two patients with CIS (31 female, 11 male) and 65 age and sex
      matched HC (41 female, 24 male) were scanned on a 3T scanner. Mean age was 40.1
      (SD = 10.4) years in patients with CIS, and 42.8 (SD = 14) years in HC, while
      mean disease duration was 1.2 years (SD = 1.3) in patients with CIS. MP-APT,
      NPTV, and normalized volume measurements were derived for all SDGM structures.
      Parametric and nonparametric group-wise comparisons were performed, and
      associations were determined with other MR imaging  metrics. RESULTS: Patients
      with CIS had significantly increased MP-APT (P = .029) and MP-APT volume (P =
      .045) in the pulvinar nucleus of the thalamus compared with HC. Furthermore, the
      putamen (P = .004), caudate (P = .035), and total SDGM (P = .048) displayed
      significant increases in MP-APT volume, while MP-APT was also significantly
      increased in the putamen (P = .029). No global or regional volumetric MR imaging
      differences were found between the study groups. Significant correlations were
      observed between increased MP-APT volumes of total SDGM, caudate, thalamus,
      hippocampus, and substantia nigra with white matter atrophy and increased T2
      lesion volume (P <  .05). CONCLUSION: Patients with CIS showed significantly
      increased content and volume of iron, as determined by abnormal SWI-phase
      measurement, in the various SDGM structures, suggesting that iron deposition may
      precede structure-specific  atrophy.

PMID- 22460344
TI  - Somatotopic organization of motor pathways in the internal capsule: a
      probabilistic diffusion tractography study.
AB  - BACKGROUND AND PURPOSE: The location of the motor pathways in the PLIC remains
      controversial. In the current study, we trace the fibers from the tongue, face,
      hand, and foot motor cortices by using probabilistic diffusion tractography and
      define their somatotopic organization in the PLIC. MATERIALS AND METHODS: Twenty
      subjects were retrospectively studied. Fiber tracts were separately calculated
      between ROIs in the cerebral peduncle and in the 4 different motor regions in the
      precentral gyrus. Probabilistic connectivity maps were generated, and the voxel
      with the highest probability was designated as the position of the motor pathway.
      The PI and LI were defined as the relative anteroposterior and mediolateral
      locations of the motor pathways. RESULTS: Tongue pathways were located
      anteromedial to face in 16 hemispheres (40%), with P < .05 for the PI and LI.
      Face pathways were located anteromedial to hand in 25 hemispheres (62.5%) with P
      < .05 for PI and LI. Hand pathways were anteromedial to foot in 14 hemispheres
      (35%) and anterior in 11 hemispheres (27.5%), with P < .05 for PI but P > .13 for
      LI. Group analysis showed that the somatotopic arrangement of the bilateral
      hemispheres was symmetric. CONCLUSIONS: Probabilistic tractography demonstrated
      the anteroposterior alignment of the motor pathways along the long axis in the
      PLIC. Probabilistic tractography successfully tracked the motor pathways of the
      tongue, face, hand, and foot from the precentral gyrus through their intersection
      with the larger superior longitudinal fasciculus to the PLIC in all cases,
      overcoming limitations of standard (nonprobabilistic) tractography methods.

PMID- 22460345
TI  - Verbal-autopsy-based projection of cancer deaths in India.

PMID- 22460346
TI  - Cancer mortality in India: a nationally representative survey.
AB  - BACKGROUND: The age-specific mortality rates and total deaths from specific
      cancers have not been documented for the various regions and subpopulations of
      India. We therefore assessed the cause of death in 2001-03 in homes in small
      areas that were chosen to be representative of all the parts of India. METHODS:
      At least 130 trained physicians independently assigned causes to 122,429 deaths,
      which occurred in 1.1 million homes in 6671 small areas that were randomly
      selected to be representative of all of India, based on a structured non-medical
      surveyor's field report. FINDINGS: 7137 of 122,429 study deaths were due to
      cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400
      (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300
      women). At 30-69 years, the three most common fatal cancers were oral (including
      lip and pharynx, 45,800 [22.9%]), stomach (25,200 [12.6%]), and lung (including
      trachea and larynx, 22,900 [11.4%]) in men, and cervical (33,400 [17.1%]),
      stomach (27,500 [14.1%]), and breast (19,900 [10.2%]) in women. Tobacco-related
      cancers represented 42.0% (84,000) of male and 18.3% (35,700) of female cancer
      deaths and there were twice as many deaths from oral cancers as lung cancers. Age
      standardised cancer mortality rates per 100,000 were similar in rural (men 95.6
      [99% CI 89.6-101.7] and women 96.6 [90.7-102.6]) and urban areas (men 102.4 [92.7
      112.1] and women 91.2 [81.9-100.5]), but varied greatly between the states, and
      were two times higher in the least educated than in the most educated adults
      (men, illiterate 106.6 [97.4-115.7] vs most educated 45.7 [37.8-53.6]; women,
      illiterate 106.7 [99.9-113.6] vs most educated 43.4 [30.7-56.1]). Cervical cancer
      was far less common in Muslim than in Hindu women (study deaths 24, age
      standardised mortality ratio 0.68 [0.64-0.71] vs 340, 1.06 [1.05-1.08]).
      INTERPRETATION: Prevention of tobacco-related and cervical cancers and earlier
      detection of treatable cancers would reduce cancer deaths in India, particularly
      in the rural areas that are underserved by cancer services. The substantial
      variation in cancer rates in India suggests other risk factors or causative
      agents that remain to be discovered. FUNDING: Bill & Melinda Gates Foundation and
      US National Institutes of Health.

PMID- 22460347
TI  - Use of bioabsorbable pins in surgical fixation of comminuted periarticular
      fractures.
AB  - OBJECTIVES: To determine if bioabsorbable pins can be used for stabilization of
      comminuted articular fragments in periarticular fractures with adequate quality
      of fixation, while eliminating the potential complications related to use of
      traditional implants. DESIGN: Multicenter retrospective review. SETTING: Two
      Level 1 trauma centers. PATIENTS/PARTICIPANTS: Institutional billing records
      identified all cases (83) in which bioabsorbable pins were implanted. All charts
      were reviewed, and all periarticular fracture cases (80 fractures in 78 patients)
      were included. INTERVENTION: Open reduction and internal fixation of highly
      comminuted periarticular fractures, using bioabsorbable poly-p-dioxanone and poly
      l-lactic acid pins to stabilize the fragments of articular surface. MAIN OUTCOME
      MEASUREMENTS: Outcomes were determined by maintenance of articular reduction
      assessed at 6 weeks and 3 months; development of posttraumatic arthritis assessed
      radiographically and by clinical examination at 1 year postoperatively; and rates
      of local complications including infection, pin migration, and pin-related soft
      tissue complications evaluated by complete medical record review. RESULTS: No
      patients showed loss of articular reduction at 6 weeks or 3 months. There were no
      pin-related local complications or pin migration and no instances of delayed
      union or nonunion. Radiographs showed 19% arthritic changes at 12 months, with
      16% loss to follow-up. Infection rate was 6%. CONCLUSIONS: In highly comminuted
      periarticular fractures, bioabsorbable pins are an intriguing alternative to
      traditional fixation methods. They afford similar effectiveness in maintaining
      stability without evidence of pin migration or other concerns of buried metallic
      implants.

PMID- 22460348
TI  - Facile synthesis of fluorescent dye labeled biocompatible polymers via immortal
      ring-opening polymerization.
AB  - A highly efficient strategy for synthesizing "clean" fluorescent dye-labeled
      biocompatible polymers was established by employing a rare-earth metal catalyst
      via immortal ROP.

PMID- 22460350
TI  - Sequencing-based detection of drug-resistant Mycobacterium tuberculosis in
      patients with spinal tuberculosis.
AB  - INTRODUCTION: Traditionally, bacterial cultures serve as the gold standard for
      the detection of drug resistance and can provide evidence for directing the
      treatment of tuberculosis. However, this method has a low positive rate and is
      time consuming, which significantly limits its wide application. Thus, in the
      present study, the genes associated with drug resistance were amplified and
      sequenced to determine the presence of drug-resistant mutations in Mycobacterium
      tuberculosis. In addition, to find a more sensitive, specific, rapid, and simple
      method for the detection of drug-resistant bacteria, this method was compared
      with traditional bacterial culture. MATERIALS AND METHODS: Pus was collected from
      surgical patients with spinal tuberculosis. The common drug resistance genes
      (rpoB, rpsL, and katG) were amplified by PCR. The PCR products were then
      sequenced, and the sequences were compared with those in the NCBI database using
      DNATools v.5.1 software. RESULTS: Mutations were identified in 17 patients,
      including mutations in the rpsL gene in four patients, the rpoB gene in seven,
      and the katG gene in six. The mean time of detection was 6 days. CONCLUSION:
      These results indicated that PCR and DNA sequencing are rapid, sensitive, and
      specific methods for the detection of drug-resistant genes of M. tuberculosis in
      patients with spinal tuberculosis. This method may provide critical evidence for
      the clinical treatment of tuberculosis when it is applied in combination with
      bacterial culture.

PMID- 22460349
TI  - High mitochondrial mutation rates estimated from deep-rooting Costa Rican
      pedigrees.
AB  - Estimates of mutation rates for the noncoding hypervariable Region I (HVR-I) of
      mitochondrial DNA vary widely, depending on whether they are inferred from
      phylogenies (assuming that molecular evolution is clock-like) or directly from
      pedigrees. All pedigree-based studies so far were conducted on populations of
      European origin. In this article, we analyzed 19 deep-rooting pedigrees in a
      population of mixed origin in Costa Rica. We calculated two estimates of the HVR
      I mutation rate, one considering all apparent mutations, and one disregarding
      changes at sites known to be mutational hot spots and eliminating genealogy
      branches which might be suspected to include errors, or unrecognized adoptions
      along the female lines. At the end of this procedure, we still observed a
      mutation rate equal to 1.24 * 10(-6) , per site per year, i.e., at least
      threefold as high as estimates derived from phylogenies. Our results confirm that
      mutation rates observed in pedigrees are much higher than estimated assuming a
      neutral model of long-term HVRI evolution. We argue that until the cause of these
      discrepancies will be fully understood, both lower estimates (i.e., those derived
      from phylogenetic comparisons) and higher, direct estimates such as those
      obtained in this study, should be considered when modeling evolutionary and
      demographic processes.

PMID- 22460351
TI  - Cervical lateral mass screw fixation without fluoroscopic control: analysis of
      risk factors for complications associated with screw insertion.
AB  - OBJECTIVE: To examine the outcome of cervical lateral mass screw fixation
      focusing on analysis of the risk factors for screw-related complications.
      METHODS: Ninety-four patients who underwent posterior cervical fixation with a
      total of 457 lateral mass screws were included in the study. The lateral mass
      screws were placed using a modified Magerl method. Computed tomographic (CT)
      images were taken in the early postoperative period in all patients, and the
      screw trajectory angle was measured on both axial and sagittal plane images.
      RESULTS: In the postoperative CT analysis for the screw trajectory, 56.5 % of the
      screws were directed within the acceptable range (within 21-40 degrees  on both
      axial and sagittal planes). As intraoperative screw-associated complications, 9.6
      % of the screws were found to contact with or breach the vertebral artery
      foramen. In this group, the screw trajectory angle on axial plane was
      significantly lower than in the group without contact. Facet violation was
      observed in 13 screws (2.8 %). This complication was associated with a
      significantly lower trajectory angles in the sagittal plane, predominantly at C6
      level (69.2 %). In the patient chart review, no serious neurovascular injuries
      were documented. CONCLUSIONS: In the analysis of potential risk factors for
      violation of the VA foramen as well as FV during screw insertion, the former
      incidence was significantly related to the screw trajectory angle (lack of
      lateral angulation) in the axial plane, while the latter incidence was related to
      a poor screw trajectory angle in the sagittal plane.

PMID- 22460352
TI  - Reducing the rate of early primary hip dislocation by combining a change in
      surgical technique and an increase in femoral head diameter to 36 mm.
AB  - INTRODUCTION: We report how changes to our total hip arthroplasty (THA) surgical
      practise lead to a decrease in early hip dislocation rates. METHODS: Group B
      consisted of 421 consecutive primary THA operations performed via a posterior
      approach. The operative technique included a meticulous repair of the posterior
      capsule, alignment of the acetabular cup with the transverse acetabular ligament
      (TAL) and a 36-mm-diameter femoral head. We compared the dislocation rates and
      cost implications of this technique to a historical control Group A consisting of
      389 patients. The control group had their THA performed with no repair of the
      capsule, no identification of the TAL and all received a 28-mm-diameter head. Our
      primary outcome is the rate of early hip dislocation and we hypothesised that we
      can reduce the rate of early hip dislocation with this new regime. RESULTS: In
      Group B there were no early dislocations (within 6 months) and two (0.5 %)
      dislocations within 18 months; minimum follow-up time was 18 months with a range
      of (18-96 months). This compared to a 1.8 % early dislocation rate and a 2.6 %
      rate at 18 months in Group A; minimum follow-up time was 60 months with a range
      of (60-112 months). These results were statistically significant (p = 0.006).
      CONCLUSION: We suggest that when primary hip arthroplasty is performed through a
      posterior approach, a low early dislocation rate can be achieved using the
      described methods.

PMID- 22460353
TI  - Copper-catalyzed oxidation of azolines to azoles.
AB  - We report herein convenient, aerobic conditions for the oxidation of thiazolines
      to thiazoles and data regarding the oxidation mechanism. These reactions feature
      operationally simple and environmentally benign conditions and proceed in good
      yield to afford the corresponding azoles, thus enabling the inexpensive
      preparation of valuable molecular building blocks. Incorporation of a novel
      diimine-ligated copper catalyst, [((Mes)DAB(Me))Cu(II)(OH(2))(3)](2+) [(
      )OTf](2), provides increased reaction efficiency in many cases. In other cases
      copper-free conditions involving a stoichiometric quantity of base affords
      superior results.

PMID- 22460354
TI  - Impact of dental atmosphere and behaviour of the dentist on children's
      cooperation.
AB  - During dental treatment children are usually under psychological pressure. With
      the Sarnat Behaviour Score five different types of patients can be distinguished.
      There is no method that measures the impact of dental atmosphere and dentist's
      behaviour on the young patients' readiness to cooperate. The objective of the
      present study was the implementation and evaluation of a questionnaire on this
      subject. Eighty-eight patients participated in this study. In the first part of
      the new questionnaire personal information was collected. The second part
      consists of 43 items and investigates the relationship between dentist and
      patient and reflects the atmosphere of the environment. Statistical analysis was
      performed using the Chi-square test. There were statistically significant
      differences between the cooperative and non-cooperative group, as regards the
      perceived honesty of the dentist, the ability to explain and wish to help.
      Uncooperative children are significantly more often afraid of the dental
      environment. Sympathy alone has only a minor effect on children's cooperation.
      Children should be treated with empathy. Especially younger patients appreciate
      detailed explanations by the dentist. Children's non-cooperative behaviour
      results often from their aroused interest in the unknown environment, which
      causes an unpleasant perception of the whole setting.

PMID- 22460356
TI  - An update on pediatric bleeding disorders: bleeding scores, benign joint
      hypermobility, and platelet function testing in the evaluation of the child with
      bleeding symptoms.
AB  - Evaluating a child with symptoms of easy bruising and/or bleeding remains a
      challenge in pediatric hematology, and there is no "one size fits all" approach.
      This review focuses on recent research in three elements of the evaluation of a
      child with a suspected bleeding disorder. We will first discuss the development
      of the standardized Pediatric Bleeding Questionnaire, and its applications in
      research and clinical settings. We will then discuss the relationship between
      benign hypermobility syndromes and hemostasis, and the importance of including a
      Beighton Score in the physical examination of any child presenting with unusual
      bruising or bleeding. While prolonged bleeding times and abnormal platelet
      aggregation are common findings in children with benign hypermobility, normal
      coagulation studies do not exclude the presence of a connective tissue disorder
      in a child presenting with easy bleeding and joint hypermobility on examination.
      Finally, we will discuss the current state of knowledge regarding the laboratory
      evaluation of platelet function in children. Platelet function disorders are
      among the most common inherited bleeding disorders. However, testing for such
      disorders is time-consuming and requires a step-wise approach. We will review the
      indications for and limitations of the most commonly utilized platelet function
      laboratory studies.

PMID- 22460357
TI  - The role of FK506-binding proteins 12 and 12.6 in regulating cardiac function.
AB  - Specifically, FK506-binding proteins 12 (FKBP12) and 12.6 (FKBP12.6) are cis
      trans peptidyl prolyl isomerases that are expressed in the heart. Both FKBP12 and
      FKBP12.6 were previously known to interact with ryanodine receptors in striated
      muscles. Although FKBP12 is abundantly present in the heart, its function in the
      heart is largely uncertain. Recently, by generating FKBP12 transgenic
      overexpression and cardiac-restricted knockout mice, we showed that FKBP12 is
      critically important in regulating trans-sarcolemmal ionic currents,
      predominately the voltage-gated Na+ current, I(Na), but it appears to be less
      important for regulating cardiac ryanodine receptor function. Similar genetic
      approaches also confirm the role of FKBP12.6 in regulating cardiac ryanodine
      receptors. The current study demonstrated that FKBP12 and FKBP12.6 have very
      different physiologic functions in the heart.

PMID- 22460358
TI  - Optical mapping in the developing zebrafish heart.
AB  - Understanding the developmental basis of cardiac electrical activity has proven
      technically challenging, largely as a result of the inaccessible nature of the
      heart during cardiogenesis in many organisms. The emergence of the zebrafish as a
      model organism has availed the very earliest stages of heart formation to
      experimental exploration. The zebrafish also offers a robust platform for genetic
      and chemical screening. These tools have been exploited in screens for modifiers
      of cardiac electrophysiologic phenotypes and in screens for novel drugs.

PMID- 22460359
TI  - Cardiac sodium channel Nav1.5 mutations and cardiac arrhythmia.
AB  - As a major cardiac voltage-gated sodium channel isoform in the heart, the Nav1.5
      channel is essential for cardiac action potential initiation and subsequent
      propagation throughout the heart. Mutations of Nav1.5 have been linked to a
      variety of cardiac diseases such as long QT syndrome (LQTs), Brugada syndrome,
      cardiac conduction defect, atrial fibrillation, and dilated cardiomyopathy. The
      mutagenesis approach and heterologous expression systems are most frequently used
      to study the function of this channel. This review focuses primarily on recent
      findings of Nav1.5 mutations associated with type 3 long QT syndrome (LQT3) in
      particular. Understanding the functional changes of the Nav1.5 mutation may offer
      critical insight into the mechanism of long QT3 syndrome. In addition, this
      review provides the updated information on the current progress of using various
      experimental model systems to study primarily the long QT3 syndrome.

PMID- 22460360
TI  - Posttraumatic growth in patients who survived cardiac surgery: the predictive and
      mediating roles of faith-based factors.
AB  - Despite the growing knowledge of posttraumatic growth, only a few studies have
      examined personal growth in the context of cardiac health. Similarly,
      longitudinal research is lacking on the implications of religion/spirituality for
      patients with advanced cardiac diseases. This paper aims to explore the effect of
      preoperative religious coping on long-term postoperative personal growth and
      potential mediation in this effect. Analyses capitalized on a preoperative survey
      and medical indices from the Society of Thoracic Surgeons' National Database of
      patients undergoing cardiac surgery. Participants in the current follow-up study
      completed a mailed survey 30 months after surgery. Hierarchical regression
      analysis was performed to evaluate the extent to which preoperative use of
      religious coping predicted growth at follow-up, after controlling for key
      demographics, medical indices, mental health, and protective factors. Predictors
      of posttraumatic growth at follow-up were positive religious coping and a living
      status without a partner. Medical indices, optimistic expectations, social
      support, and other religious factors were unrelated to posttraumatic growth.
      Including religious factors diminished effects of gender, age, and race.
      Including perceived spiritual support completely eliminated the role of positive
      religious coping, indicating mediation. Preoperative positive religious coping
      may have a long-term effect on postoperative personal growth, explainable by
      higher spiritual connections as a part of significance-making. These results
      suggest that spirituality may play a favorable role in cardiac patients'
      posttraumatic growth after surviving a life-altering operation. The elimination
      of demographic effects may help explain previously mixed findings concerning the
      association between these factors and personal growth.

PMID- 22460361
TI  - Adolescent sunscreen use in springtime: a prospective predictive study informed
      by a belief elicitation investigation.
AB  - Two studies aimed to understand springtime sunscreen use amongst adolescents and
      to compare the predictive utility of the theory of planned behavior, descriptive
      norms, prototype perceptions and planning. In Study 1, a belief elicitation study
      with N = 67 adolescents identified beliefs about, and strategies for, sunscreen
      use. In Study 2, N = 177 adolescents completed measures of direct and belief
      based theory of planned behavior measures prototype evaluation and similarity,
      descriptive norms and planning. Sunscreen use was reported 2 months later. In
      Study 1, sunburn prevention and skin care emerged as the most relevant
      consequences of sunscreen use. Facilitators were supportive family norms.
      Sunscreen properties, costs and forgetting were main barriers which were commonly
      addressed with preparatory actions such as carrying sunscreen. In Study 2,
      gender, intention and prototype evaluation were predictive of sunscreen use.
      Positive evaluations of those who use sunscreen were related to lower sunscreen
      use when controlling for intention, descriptive norm and gender. Belief-based
      measures were the best predictors of intention. Behavioral, normative and control
      beliefs are crucial for understanding sunscreen. Future interventions should
      focus on these beliefs to change intentions.

PMID- 22460362
TI  - Comparison of imaging modalities in pediatric thyroglossal duct cysts.
AB  - OBJECTIVES/HYPOTHESIS: To determine and compare the accuracy of different imaging
      modalities including ultrasound (US), magnetic resonance imaging (MRI), and
      computed tomography (CT) in the diagnosis of thyroglossal duct cysts (TGDC) in
      children. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective
      chart review was performed on patients under the age of 18 years who had
      undergone surgical excision of midline neck masses between January 2002 and June
      2011. All patients had preoperative imaging. Data including age at surgery,
      preoperative imaging results, and postoperative pathology results were recorded.
      Preoperative imaging diagnoses were then compared to postoperative pathologic
      diagnoses. Diagnostic test statistics were performed. RESULTS: A total of 44
      patients met the study criteria. There were 15 patients who underwent more than
      one modality of imaging study. US had a sensitivity of 75% in diagnosis of TGDC.
      MRI sensitivity was 60% and CT was 82%. None of the tests had high specificity
      for TGDC; US was the highest at 80%. All three modalities had positive predictive
      values higher than 90%. US had the highest positive likelihood ratio (3.8),
      although the 95% confidence interval was not statistically significant.
      CONCLUSIONS: In a comparison of the three most commonly used imaging modalities
      for pediatric TGDC, US was the preferred exam given its comparable accuracy, ease
      of administration, and lower cost. In addition, the added risks of general
      anesthesia with MRI and ionizing radiation with CT are not justified in this
      setting given their equivalent or inferior performance when compared to US in
      this cohort.

PMID- 22460363
TI  - Light aerobic physical exercise in combination with leucine and/or glutamine-rich
      diet can improve the body composition and muscle protein metabolism in young
      tumor-bearing rats.
AB  - Nutritional supplementation with some amino acids may influence host's responses
      and also certain mechanism involved in tumor progression. It is known that
      exercise influences body weight and muscle composition. Previous findings from
      our group have shown that leucine has beneficial effects on protein composition
      in cachectic rat model as the Walker 256 tumor. The main purpose of this study
      was to analyze the effects of light exercise and leucine and/or glutamine-rich
      diet in body composition and skeletal muscle protein synthesis and degradation in
      young tumor-bearing rats. Walker tumor-bearing rats were subjected to light
      aerobic exercise (swimming 30 min/day) and fed a leucine-rich (3%) and/or
      glutamine-rich (4%) diet for 10 days and compared to healthy young rats. The
      carcasses were analyzed as total water and fat body content and lean body mass.
      The gastrocnemious muscles were isolated and used for determination of total
      protein synthesis and degradation. The chemical body composition changed with
      tumor growth, increasing body water and reducing body fat content and total body
      nitrogen. After tumor growth, the muscle protein metabolism was impaired, showing
      that the muscle protein synthesis was also reduced and the protein degradation
      process was increased in the gastrocnemius muscle of exercised rats. Although
      short-term exercise (10 days) alone did not produce beneficial effects that would
      reduce tumor damage, host protein metabolism was improved when exercise was
      combined with a leucine-rich diet. Only total carcass nitrogen and protein were
      recovered by a glutamine-rich diet. Exercise, in combination with an amino acid
      rich diet, in particular, leucine, had effects beyond reducing tumoral weight
      such as improving protein turnover and carcass nitrogen content in the tumor
      bearing host.

PMID- 22460364
TI  - gamma-Tocopherol inhibits human prostate cancer cell proliferation by up
      regulation of transglutaminase 2 and down-regulation of cyclins.
AB  - To establish a system to study differentiation therapy drugs, we used the
      androgen-independent human prostate PC-3 tumor cell line as a target and alpha-
      and gamma-tocopherol as inducers. Effects of alpha- and gamma-tocopherol on the
      cell cycle, proliferation and differentiation, were examined. A more significant
      growth inhibition activity for gamma- than for alpha-tocopherol was observed.
      Flow cytometry analysis of alpha- and gamma-tocopherol-treated prostate carcinoma
      PC3 cells showed decreased progression into the S-phase. This effect,
      particularly evident for gamma-tocopherol, was associated with an up-regulation
      and increased activity of transglutaminase 2 (TG2), a reduced DNA synthesis and a
      remarkable decreased levels of cyclin D1 and cyclin E. Activation of TG2 suggests
      that gamma-tocopherol has an evident differentiative capacity on PC3 cells,
      leading to an increased expression of TG2, and reduced cyclin D1 and cyclin E
      levels, affecting cell cycle progression. It is feasible that up-regulation and
      activation of TG2, associated with a reduced proliferation, are parts of a large
      scale reprogramming that can attenuate the malignant phenotype of PC3 cells in
      vitro. These data suggest further investigation on the potential use of this
      gamma-form of vitamin E as a differentiative agent, in combination with the
      common cytotoxic treatments for prostate cancer therapy.

PMID- 22460365
TI  - Measures of angular spread and entropy for the detection of architectural
      distortion in prior mammograms.
AB  - PURPOSE: Architectural distortion is an important sign of early breast cancer. We
      present methods for computer-aided detection of architectural distortion in
      mammograms acquired prior to the diagnosis of breast cancer in the interval
      between scheduled screening sessions. METHODS: Potential sites of architectural
      distortion were detected using node maps obtained through the application of a
      bank of Gabor filters and linear phase portrait modeling. A total of 4,224
      regions of interest (ROIs) were automatically obtained from 106 prior mammograms
      of 56 interval-cancer cases, including 301 true-positive ROIs, and from 52
      mammograms of 13 normal cases. Each ROI was represented by three types of entropy
      measures of angular histograms composed with the Gabor magnitude response, angle,
      coherence, orientation strength, and the angular spread of power in the Fourier
      spectrum, including Shannon's entropy, Tsallis entropy for nonextensive systems,
      and Renyi entropy for extensive systems. RESULTS: Using the entropy measures with
      stepwise logistic regression and the leave-one-patient-out method for feature
      selection and cross-validation, an artificial neural network resulted in an area
      under the receiver operating characteristic curve of 0.75. Free-response receiver
      operating characteristics indicated a sensitivity of 0.80 at 5.2 false positives
      (FPs) per patient. CONCLUSION: The proposed methods can detect architectural
      distortion in prior mammograms taken 15 months (on the average) before clinical
      diagnosis of breast cancer, with a high sensitivity and a moderate number of FPs
      per patient. The results are promising and may be improved with additional
      features to characterize subtle abnormalities and larger databases including
      prior mammograms.

PMID- 22460366
TI  - Immediate effects of the high-pitched blowing vocal exercise.
AB  - PURPOSE: To investigate the immediate effects of the high-pitched blowing vocal
      exercise. METHODS: This is a comparative observational study. Participants were
      46 women with ages between 25 and 45 years, who were divided into two groups: 23
      individuals with vocal complaint (VCG), and 23 without vocal complaint (WVCG).
      The procedures included vocal auditory-perceptual analysis, acoustic analysis,
      videostroboscopy, and vocal self-assessment before and after ten repetitions of
      the high-pitched blowing vocal exercise. The auditory-perceptual analysis and the
      assessment of the laryngeal configuration images were carried out by three speech
      language pathologists, who performed the blind analysis of two vocal samples of
      each subject, marking the best sample. The acoustic parameters measured were
      fundamental frequency, jitter and shimmer in sustained vowel, and fundamental
      frequency in speech. For the vocal self-assessment, participants were asked the
      question: "How do you think your voice is after the exercise?". RESULTS: Both
      groups presented better voice quality in the auditory-perceptual analysis after
      the exercise. In the acoustic analysis, shimmer values reduced for both groups,
      and jitter values reduced only for the WVCG post-exercise. It was observed
      increase of the fundamental frequency in the VCG in the sustained vowel. The
      videostroboscopy showed better glottal closure and less vestibule involvement for
      both groups after the exercise. Vocal self-assessment indicated better voice
      emission post-exercise in the VCG. CONCLUSION: The high-pitched blowing vocal
      exercise produces positive immediate effects observed in auditory-perceptual,
      acoustic, and laryngeal analyses and in vocal self-assessment.

PMID- 22460367
TI  - Group speech-language pathology intervention in popular singers: prospective
      controlled study.
AB  - PURPOSE: To assess the benefits of a group vocal improvement program to popular
      singers without voice disorders. METHODS: This is a quasi-experimental
      intervention study, carried out with 37 popular singers of both genders, with
      ages between 18 and 40 years and adapted vocal quality. Participants were divided
      into two groups: Intervention (IG) and Control (CG). The IG included 21 subjects
      who participated in seven weekly lectures regarding anatomy and physiology of the
      vocal tract, vocal hygiene care, and vocal exercises for voice improvement. The
      CG included 16 participants, who maintained their normal activities during this
      period, and did not receive any orientations regarding vocal improvement. In pre-
      and post-intervention, all participants answered a questionnaire about habits and
      demands related to the voice, and were evaluated regarding resonance, speech
      articulation, voice projection, pitch, loudness, maximum phonation time, and s/z
      ratio. RESULTS: The vocal training was positive in the perception of the singers,
      who reported improvement in their voices. The assessment of maximum phonation
      time and s/z ratio did not present differences between groups (p=0.57). No
      modifications of behaviors potentially harmful to the vocal health were observed
      within 60 days after the intervention (p=0.24). There was also no considerable
      decrease of voice complaints (p=0.1), although the decrease percentage of
      complaints in the IG (22.2%) was higher than that of the CG (11.1%). CONCLUSION:
      Group vocal training intervention in popular singers is positive regarding the
      perception of the individual about his/her voice production, even though they
      presented adapted voice from the beginning of the process.

PMID- 22460368
TI  - Impact of auditory training for perceptual assessment of voice executed by
      undergraduate students in Speech-Language Pathology.
AB  - PURPOSE: To analyze the impact of auditory training for auditory-perceptual
      assessment carried out by Speech-Language Pathology undergraduate students.
      METHODS: During two semesters, 17 undergraduate students enrolled in theoretical
      subjects regarding phonation (Phonation/Phonation Disorders) analyzed samples of
      altered and unaltered voices (selected for this purpose), using the GRBAS scale.
      All subjects received auditory training during nine 15-minute meetings. In each
      meeting, a different parameter was presented using the different voices sample,
      with predominance of the trained aspect in each session. Sample assessment using
      the scale was carried out before and after training, and in other four
      opportunities throughout the meetings. Students' assessments were compared to an
      assessment carried out by three voice-experts speech-language pathologists who
      were the judges. To verify training effectiveness, the Friedman's test and the
      Kappa index were used. RESULTS: The rate of correct answers in the pre-training
      was considered between regular and good. It was observed maintenance of the
      number of correct answers throughout assessments, for most of the scale
      parameters. In the post-training moment, the students showed improvements in the
      analysis of asthenia, a parameter that was emphasized during training after the
      students reported difficulties analyzing it. There was a decrease in the number
      of correct answers for the roughness parameter after it was approached segmented
      into hoarseness and harshness, and observed in association with different
      diagnoses and acoustic parameters. CONCLUSION: Auditory training enhances
      students' initial abilities to perform the evaluation, aside from guiding
      adjustments in the dynamics of the university subject.

PMID- 22460369
TI  - Auditory rehabilitation effects on the temporal ordering ability in elderly
      hearing aids users.
AB  - PURPOSE: To analyze the effects of an auditory rehabilitation program for the
      temporal ordering ability, of duration and pitch patterns of sounds, in elderly
      hearing aids users. METHODS: Participants were 17 elderly people, with ages
      between 60 and 84 years, divided into Control Group (CG), which only used hearing
      aids, and Study Group (SG), which were submitted to an auditory rehabilitation
      program that included auditory counseling and training. All subjects were
      assessed at the beginning and at the end of the study, through the Duration
      Pattern Sequence and Pitch Pattern Sequence tests. The period between assessments
      was seven weeks. RESULTS: In the Duration Pattern Sequence test, CG subjects
      showed mean values of accuracy in the murmured condition of 48.64 and 54.43%, for
      initial and final assessments, respectively; SG subjects, presented 60.39 and
      76.28%. In the named condition, CG presented 51.93 and 52.43%, and SG, 63.94 and
      77.44% for initial and final assessments, respectively. In the Pitch Pattern
      Sequence test, CG subjects showed mean values of accuracy in the murmured
      condition of 80.62 and 79.94%, and SG subjects, of 79.78 and 90.39%, for initial
      and final assessments, respectively. In the named the condition, CG presented
      82.64 and 84.21%, and SG, 82.94 and 85.89%, for initial and final assessments.
      There was a difference only for SG subjects in the murmured and named conditions
      of the Duration Pattern Sequence test, in the named condition of the Pitch
      Pattern Sequence test, indicating higher mean values in the final assessment.
      CONCLUSION: The auditory rehabilitation program to elderly hearing aid users
      provide satisfactory improvement in recognition, temporal ordering, and naming of
      duration and pitch patterns of sounds.

PMID- 22460370
TI  - Software use in the (re)habilitation of hearing impaired children.
AB  - PURPOSE: To verify the applicability of a software in the (re)habilitation of
      hearing impaired children. METHODS: The sample comprised 17 children with hearing
      impairment, ten with cochlear implants (CI) and seven with hearing aids (HA). The
      Software Auxiliar na Reabilitacao de Disturbios Auditivos - SARDA (Auxiliary
      Software for the Rehabilitation of Hearing Disorders) was used. The training
      protocol was applied for 30 minutes, twice a week, for the necessary time to
      complete the strategies proposed in the software. To measure the software's
      applicability for training the speech perception ability in quiet and in noise,
      subjects were assessed through the Hearing in Noise Test (HINT), before and after
      the auditory training. Data were statistically analyzed. RESULTS: The group of CI
      users needed, in average, 12.2 days to finish the strategies, and the group of HA
      users, in average 10.14 days. Both groups presented differences between pre and
      post assessments, both in quiet and in noise. Younger children showed more
      difficulty executing the strategies, however, there was no correlation between
      age and performance. The type of electronic device did not influence the
      training. Children presented greater difficulty in the strategy involving non
      verbal stimuli and in the strategy with verbal stimuli that trains the sustained
      attention ability. Children's attention and motivation during stimulation were
      fundamental for a successful auditory training. CONCLUSION: The auditory training
      using the SARDA was effective, providing improvement of the speech perception
      ability, both in quiet and in noise, for the hearing impaired children.

PMID- 22460371
TI  - Temporal processing in children with phonological disorders submitted to auditory
      training: a pilot study.
AB  - PURPOSE: This study compared the temporal processing performance of children with
      phonological disorders submitted to formal and informal auditory training.
      METHODS: Fifteen subjects with phonological disorder (pure tone thresholds <=20
      dBHL from 0.50 to 4 kHz, and age between 7 years and 10 years and 11 months) were
      evaluated, divided into three groups: CONTROL GROUP: five subjects (mean age 9.1
      years) without auditory processing disorder, who passed through two evaluations
      of the auditory processing at intervals of six to eight weeks and without any
      intervention; Formal Training Group with five subjects (average 8.3 years) with
      auditory processing disorder submitted to eight sessions of formal training; and
      Informal Training Group, with five subjects (average 8.1 years) with auditory
      processing disorder submitted to eight sessions of informal training. RESULTS:
      After eight sessions the formal training group showed an improvement of 8% and
      the informal training group of 22.5% in comparison with the pitch pattern
      sequence test. For the duration pattern sequence test, the average of the formal
      training group improved by 12.9% and the informal training group by 18.7%. There
      was no statistical difference between the means obtained by both groups after
      intervention, neither in the pitch pattern nor in the duration pattern sequence
      test. CONCLUSION: Although the results did not present significant differences,
      this pilot study suggests that both formal and informal trainings provide
      improvement in the temporal processing abilities of children with phonological
      and auditory processing disorders.

PMID- 22460372
TI  - Stimulability: auxiliary measure in the identification of difficulty in speech
      sounds production.
AB  - PURPOSE: To analyze the effectiveness of stimulability as a complementary task to
      the diagnosis of speech sound disorders (SSD), and to describe the performance of
      children with absent sounds from the phonetic inventory according to stimulable
      absent sounds, severity, gender, age, and occurrence of different phonological
      processes. METHODS: Participants were 130 male and female children with ages
      between 5 years and 10 years and 10 months, divided into two groups: Research
      Group (RG), comprising 55 children with SSD; and Control Group (CG), composed of
      75 children with no speech and language disorders. Based on participants'
      performance on the Phonology test, the severity of the disorder was calculated
      through the Percentage of Consonants Correct - Revised (PCC-R), and the phonetic
      inventory was verified. The stimulability test was applied to each absent sound
      from the phonetic inventory, based on the imitation of single words. The RG was
      subdivided into RG1 (27 children who presented absent sounds) and RG2 (28
      children with complete inventory). RESULTS: None of the CG children presented
      absent sounds in the phonetic inventory, while 49% of the RG1 subjects presented
      absent sounds. There was absence of most language sounds. PCC-R means were lower
      for RG1, indicating higher severity. In the RG1, 22 children were stimulable,
      while five were not stimulable to any absent sound. There was association between
      the most occurring phonological processes and the need for stimulability
      assessment, indicating that the difficulty to produce absent sounds reflects
      difficulty with phonological representation. Stimulability is influenced by age,
      but not by gender. CONCLUSION: The stimulability test is effective to identify
      stimulable children among those who present absent sounds from their phonetic
      inventory. Children with SSD and absent sounds have lower PCC-R, and therefore
      present more severe disorder. Most of the children with absent sounds are
      stimulable, but may not be stimulable for complex syllable structures or
      articulatory gestures. The difficulty to produce absent sounds reflects
      phonological representation deficit. Speech production is influenced by
      maturation in both boys and girls.

PMID- 22460373
TI  - Is it possible to predict the length of therapy for developmental language
      impairments?
AB  - PURPOSE: To explore which measures could predict the persistency of developmental
      language impairment (DLI) based on the association between the initial language
      assessment and the therapeutic prognosis of the child. METHODS: In this
      retrospective study, the records of 42 children with diagnosis of DLI were
      analyzed. Participants' age varied from 21 to 63 months at the first language
      assessment, which included vocabulary, phonology, pragmatics and fluency tests.
      The performance of subjects in each test was scored from 0 to 4, based on the
      severity of the deficits, and the maximum score corresponded to age-adequate
      performance. As prognostic measure, we accounted the length of therapy (in
      sessions) of patients who were discharged, were referred to another service
      (because the deficits had become very mild), or remained in therapy (persistent
      language difficulties). RESULTS: There was association between initial assessment
      (normal or mild alterations for vocabulary and pragmatics abilities) and
      prognosis (<135 therapeutic sessions). Vocabulary was the only variable able to
      predict the length of therapy. Being classified as severe in this measure caused
      the estimate of treatment to increase, in average, 112 sessions. CONCLUSION: The
      first vocabulary assessment can contribute to predict the child's therapeutic
      prognosis. This finding is clinically and scientifically relevant to Speech
      Language Pathology, since it offers an auxiliary resource to the prognosis and
      therapeutic planning in cases of DLI.

PMID- 22460374
TI  - Analysis of oral narratives of preschool children before and after language
      stimulation.
AB  - PURPOSE: To verify the oral narrative abilities in preschoolers, before and after
      language stimulation. METHODS: Participants were 58 preschoolers. The study was
      developed in three stages: 1. Pre-stimulation stage (Moment 1) - preschoolers
      produced the first autonomous narrative based on a sequence of pictures, and the
      second under adult scaffolding; 2. Stimulation stage - it was conducted a weekly
      reading of children's stories in group, for ten weeks; 3. Post-stimulation stage
      (Moment 2): the same procedure of the first stage was repeated. The results
      analysis considered: the occurrence of central and secondary events; the
      accountable/explicable conduct, classified according to physical causes,
      moral/social rules and internal state; the attribution and rectification of false
      beliefs, analyzed by the internal state's accountable/explicable conduct.
      RESULTS: There was an increase in the occurrence of central events in Moment 2 as
      well as after the adult scaffolding, with decrease of secondary events comparing
      both moments and after the scaffolding. Regarding the accountable/explicable
      conduct, no differences were found between physical, social/moral rules, and
      internal state conducts. The internal state accountable/explicable conduct was
      predominantly found in all the autonomous narratives. CONCLUSION: Both the
      reading of children's stories and the adult scaffolding contribute to the
      increase in the occurrence of events in autonomous narratives. There is no
      variation on the type of accountable/explicable conduct in the narratives. The
      internal state accountable/explicable conduct is predominantly used by
      preschoolers.

PMID- 22460375
TI  - Phonemic awareness in students before and after language workshops.
AB  - PURPOSE: To verify the phonemic awareness performance of students before and
      after language workshops. METHODS: Phonemic awareness abilities of 49 students in
      the fourth year of Elementary School were assessed using the second part of the
      test "Phonological Awareness - Sequential Assessment Instrument" (CONFIAS). The
      exclusion criteria in the study were: presence of complaints or indicators of
      hearing and/or vision deficits; presence of neurological, behavioral and/or
      cognitive impairments. Subjects included in the study participated in both
      initial and final assessments and in at least 75% of the workshop meetings.
      According to their performance on the test, children were divided into three
      groups: initial, intermediate and advanced. Each group attended separate weekly
      workshops for stimulation of phonological and phonemic abilities. After five
      language workshops the students were reassessed. RESULTS: The phonemic awareness
      performance of students in all groups significantly improved after the workshops.
      The intermediate group presented the greater improvement in the mean number of
      correct answers. CONCLUSION: The phonemic awareness performance of students
      improves after language workshops.

PMID- 22460376
TI  - Occurrence of the repair strategy of stopping: relationship with phonological
      disorder severity and affected phonemes.
AB  - PURPOSE: To analyze the occurrence of the repair strategy of stopping in the
      different severities of phonological disorder, and to verify the phonemes most
      affected by this strategy. METHODS: Participants were 33 children, 14 female and
      19 male, aged between 4 and 8 years. All children used the repair strategy of
      stopping for at least one phoneme or allophone, with percentage equal to or
      greater than 40%. Data were selected from the first speech assessment, before
      starting intervention, and phonological disorder severity was determined by the
      Percentage of Consonants Correct-Revised. The number of children who used the
      repair strategy of stopping was accounted, analyzing the phonological disorder
      severity and the phonemes most affected by this strategy. Data were statistically
      analyzed. RESULTS: The use of the repair strategy of stopping was more observed
      for the degrees moderate-severe and severe, with 42.86% of occurrence in each
      one. No difference was found in the comparison between the types of phonemes and
      allophones affected in the sample: /s/, /f/, /f/ and /z/, /[see text]/, /v/,
      [tf]/ and [d[see text]]/, /[see text]/, and /n/. CONCLUSION: The stopping repair
      strategy is more frequent in the most severe degrees of phonological disorder.
      This strategy is used similarly by children with phonological disorders, with
      regards to the affected phonemes.

PMID- 22460377
TI  - Paradoxical vocal fold motion: respiratory retraining to manage long-term
      symptoms.
AB  - Paradoxical vocal fold motion (PVFM) is a laryngeal disorder characterized by
      abnormal adduction of the vocal folds during respiration. It is caused by a
      multitude of etiologies and their interactions. In the current study, a 24-year
      old female patient with a 12-year complaint of shortness of breath was diagnosed
      with paradoxical vocal fold motion following nasal endoscopy, spirometry testing
      and detailed case history analysis. She had no history or indication of
      laryngopharyngeal reflux or chronic cough. She performed respiratory retraining
      exercises three to four times daily for a period of four weeks, and continued
      daily exercises for two additional months as needed. After four weeks of
      treatment, abnormal vocal fold adduction continued to be seen on endoscopy and
      the patient was mildly symptomatic. One month post-treatment, there was no
      abnormal vocal fold adduction and the patient reported rare shortness of breath.
      At three months post-treatment, there was no abnormal vocal fold adduction and
      the patient no longer reported shortness of breath. She reported normal breathing
      with no symptoms one year later. The results suggest that non-pulmonary related
      shortness of breath treated with respiratory retraining can effectively eliminate
      dyspnea in patients with long term breathing difficulties caused by paradoxical
      vocal fold motion. Resolution may require treatment over an extended period of
      time.

PMID- 22460378
TI  - Phonological awareness abilities of a child with acquired immunodeficiency
      syndrome before and after speech therapy.
AB  - The aim of the present study was to characterize the phonological awareness
      abilities of a child with Acquired Immunodeficiency Syndrome (AIDS) before and
      after speech-language therapy. The participant was a 6-year-old girl, first-grade
      Elementary School student, with AIDS acquired by vertical transmission. The
      child's phonological awareness abilities were evaluated using the Instrument of
      Sequential Evaluation of Phonological Awareness (CONFIAS). After this first
      evaluation, a closed therapeutic program (15 sessions) for phonological awareness
      was developed, consisting of activities for syllabic and phonemic levels. The
      CONFIAS was reapplied in the last session in order to investigate therapy
      effectiveness. In the pre-therapy assessment, the child scored 18 points in
      syllable tasks and 1 point in phoneme tasks, with a total score of 19 points. In
      the post-therapy assessment, the child scored 26 points in syllable tasks and 11
      points in phoneme tasks, with a total score of 37 points. This study allowed us
      to characterize the performance of a child with AIDS in tasks of phonological
      awareness and the effectiveness of the therapeutic program. The score obtained
      before therapy was much lower than expected for the child's age, and presented
      significant improvement after speech-language therapy. Thus, professionals
      working with this population must be aware of therapeutic programs that approach
      phonological processing abilities in addition to other aspects.

PMID- 22460379
TI  - Analysis of the therapeutic progress of children with phonological disorders
      after the application of the Multiple Oppositions Approach.
AB  - The Multiple Oppositions Approach is described as an alternative model for the
      treatment of children with the severe phonological disorders. The aim of this
      study was to analyze the therapeutic progress of five children with phonological
      disorder, submitted to the Multiple Oppositions Approach, regarding the phonetic
      (sounds) and phonological (phonemes and altered distinctive features)
      inventories. Participants were five children with phonological disorder, with
      mean age of 6 years and 1 month. Speech data were collected through phonological
      assessment, and the Multiple Oppositions Approach was used during 25 sessions of
      intervention. Changes in the phonetic and phonological inventories (number of
      phonemes and altered distinctive features) of the subjects were analyzed. It was
      verified an increase in the number of sounds in the phonetic inventory and
      phonemes in the phonological inventory, as well as a decrease in the number of
      altered distinctive features. The Multiple Oppositions Approach allows adequate
      progress in the treatment of subjects with phonological disorders, providing an
      expansion in the phonetic (acquisition of sounds) and phonological (acquisition
      of phonemes and decrease in the number of altered distinctive features)
      inventories.

PMID- 22460380
TI  - Inclusion of individuals with special needs in regular education: a literature
      review.
AB  - PURPOSE: To critically analyze the inclusion of individuals with special needs in
      regular education in Brazil, considering social and legal aspects, through
      literature review. RESEARCH STRATEGY: The literature search was conducted in open
      access databases: LILACS, SciELO, Portal Cochrane and IUSDATA, the latter
      belonging to the Library of the Law School of the University of Sao Paulo,
      considering all articles published until December 2010. The search strategy used
      the following keywords: inclusive education; special education; inclusive
      proposal; individuals with special needs. SELECTION CRITERIA: In the search, only
      studies in which the summary or the body of the article were related to the
      purpose of the study were evaluated and selected. DATA ANALYSIS: The potentially
      relevant articles for review were presented in a protocol form containing the
      eligibility criteria of the study, methods used, characteristics of the analyzed
      group or manuscripts, type of intervention used in the study, and results
      obtained. Articles classified as expert opinions, despite their low level of
      scientific evidence, were considered in this work, since they are often found in
      the literature on the issue. RESULTS: A total of 1,399 articles was found and 120
      potentially relevant articles were selected after reading their abstracts. From
      these, 67 articles were cited in more than one database, which resulted in 53
      articles to be fully read. Fifteen of these articles were excluded after reading
      because they did not meet the inclusion criteria. Thus, 38 studies were included
      and analyzed. CONCLUSION: Following a critical analysis of the literature in the
      field, it was concluded that, so far, in general, the school receives individuals
      with special needs; however, there is a long way to go to actually include these
      individuals, although Brazil has the scope of inclusion. Therefore, it is
      necessary to establish public policies and guidelines aimed at effective
      inclusion.

PMID- 22460381
TI  - Comparing the use of the Childhood Autism Rating Scale and the Autism Behavior
      Checklist protocols to identify and characterize autistic individuals.
AB  - PURPOSE: To compare the results obtained in the Autism Behavior Checklist with
      those obtained in the Childhood Autism Rating Scale to identify and characterize
      children with Autism Spectrum Disorders. METHODS: Participants were 28 children
      with psychiatric diagnosis within the autism spectrum that were enrolled in
      language therapy in a specialized service. These children were assessed according
      to the Autism Behavior Checklist and Childhood Autism Rating Scale criteria,
      based on information obtained with parents and therapists, respectively. Data
      were statistically analyzed regarding the agreement between responses. Results
      indicating high or moderate probability of autism in the Autism Behavior
      Checklist were considered concordant with the results indicating mild-to-moderate
      or severe autism in the Childhood Autism Rating Scale. Results indicating low
      probability of autism in the Autism Behavior Checklist and without autism in the
      Childhood Autism Rating Scale were also considered concordant. RESULTS: There was
      agreement on most of the responses. Cases in which there was disagreement between
      results obtained on both protocols corroborate literature data, showing that the
      instruments may not be sufficient, if applied alone, to define the diagnosis.
      CONCLUSION: The Childhood Autism Rating Scale may not effectively diagnose
      autistic children, while the Autism Behavior Checklist may result in over-
      diagnose, including within the autism spectrum children with other disorders.
      Therefore, the associated use of both protocols is recommended.

PMID- 22460383
TI  - International Seminar on the Implementation of the World Report on Disability.

PMID- 22460384
TI  - Direct visualization of Bcl-2 family protein interactions using live cell
      fluorescent protein redistribution assays.
AB  - Bcl-2 family proteins have important roles in tumor initiation, progression and
      resistance to therapy. Pro-survival Bcl-2 proteins are regulated by their
      interactions with pro-death BH3-only proteins making these protein-protein
      interactions attractive therapeutic targets. Although these interactions have
      been extensively characterized biochemically, there is a paucity of tools to
      assess these interactions in cells. Here, we address this limitation by
      developing quantitative, high throughput microscopy assays to characterize Bcl-2
      and BH3-only protein interactions in live cells. We use fluorescent proteins to
      label the interacting proteins of interest, enabling visualization and
      quantification of their mitochondria-localized interactions. Using tool
      compounds, we demonstrate the suitability of our assays to characterize the
      cellular activity of putative therapeutic molecules that target the interaction
      between pro-survival Bcl-2 and pro-death BH3-only proteins. In addition to the
      relevance of our assays for drug discovery, we anticipate that our work will
      contribute to an improved understanding of the mechanisms that regulate these
      important protein-protein interactions within the cell.

PMID- 22460385
TI  - A double-blind randomized study comparing the efficacy and safety of a composite
      vs a conventional intravenous fat emulsion in postsurgical gastrointestinal tumor
      patients.
AB  - BACKGROUND: Composite intravenous fat emulsion, a fat emulsion composed of
      soybean oil, medium-chain triglycerides (MCT), olive oil, and fish oil, was
      evaluated for metabolic efficacy, immune modulation, clinical efficacy, safety,
      and tolerance in surgical gastrointestinal (GI) tumor patients. METHODS: In a
      prospective, randomized, double-blind study, 40 patients were randomized after
      elective digestive surgery to receive isonitrogenous, isoenergetic parenteral
      nutrition for 5 days postoperatively with either composite 20% IVFE (composed of
      soybean, MCT, olive, and fish oils) or a conventional long-chain triglyceride
      (LCT)/MCT 20% IVFE (LCT/MCT IVFE); IVFE was dosed at 1-2 g/kg body weight. Safety
      and efficacy parameters were assessed on operation day (day 0) and at the end of
      study (day 6). Adverse events were documented daily and clinical outcomes were
      recorded and compared between the groups. RESULTS: Metabolic parameters,
      laboratory parameters, proinflammatory cytokine levels, adverse events, and
      clinical outcomes did not differ between the 2 groups, with the exception that
      postoperative low-density lipoprotein levels decreased significantly in the
      composite IVFE group (93.2 +/- 24.3 vs 110.5 +/- 26.4 mg/dL, P = .038).
      CONCLUSIONS: composite IVFE was comparable with conventional LCT/MCT IVFE in
      efficacy, safety, tolerance, and clinical outcomes in surgical GI tumor patients.

PMID- 22460386
TI  - The management of adolescents with neurogenic urinary tract and bowel
      dysfunction.
AB  - Most children with neurogenic bladder dysfunction arrive into adolescence with
      reasonably managed lower urinary tract function only to experience bladder and
      kidney function deterioration after puberty. The aim of this article is to
      identify issues that contribute to adverse changes in bladder and renal function
      during adolescence and to highlight strategies to preserve urinary tract
      integrity, social continence, patient autonomy, and independence. Surveillance of
      bladder function requires patient attendance at review appointments and
      compliance with treatment plans. While encouraging independence and treatment
      compliance the clinician also needs to consider altered mental concentrating
      ability and fine motor skills of these patients. A keen eye for imminent loss of
      patient compliance to treatment protocol should be the mainstay of each encounter
      during puberty and adolescence. Annual surveillance of adolescent neurogenic
      bladder patients facilitates early identification of risk factors for urinary
      tract deterioration. Investigations include renal and bladder ultrasonography,
      urodynamic study when indicated, substantiated by videocystometry when anatomical
      status dictates. Serum creatinine should be measured and renal scintigraphy
      performed when upper urinary tract dilation, renal scarring, or atrophy are
      suspected. Optimal management of adolescents with neurologic disease of the
      urinary tract included strategies to reduce elevated detrusor pressure, maintain
      bladder compliance, and maximize dryness. Antimuscarinic medications, botulinum
      toxin A, and surgical procedures are enhanced by bowel management regimens and
      regular nurse or urotherapist patient contact. Caring for the patient as a whole
      requires discussion of sexuality, fertility status, and behaviors that increase
      the risk of progressive urinary tract damage.

PMID- 22460387
TI  - Development of a technique for in situ high temperature TEM observation of
      catalysts in a highly moisturized air atmosphere.
AB  - To clarify the influence of moisture on the structural changes of heated nano
      materials, in situ high temperature transmission electron microscopy (TEM) has
      been carried out using a conventional analytical TEM combined with a gas
      injection-specimen heating holder. Air with high moisture content, above 94%
      relative humidity (RH), from a humidifier was directly injected onto the heated
      platinum catalyst dispersed on carbon black (Pt/CB), and the morphological
      changes of the specimens were observed at high magnification dynamically. The
      result of the experiment was compared with a result obtained from an experiment
      using air with a low moisture content, 34% RH. Active movement of the Pt
      particles, leading agglomeration and grain growth, occurred prior to degradation
      of the CB support at high moisture content. In contrast, the degradation of the
      CB support leading agglomeration and grain growth of the Pt particles occurred
      before the displacement of the Pt particles on the CB supports in a low humidity
      environment.

PMID- 22460388
TI  - Three-dimensional observation of SiO2 hollow spheres with a double-shell
      structure using aberration-corrected scanning confocal electron microscopy.
AB  - Optical sectioning using scanning confocal electron microscopy (SCEM) is a new
      three-dimensional (3D) imaging technique which promises improved depth
      resolution, particularly for laterally extended objects. Using a stage-scanning
      system to move the specimen in three dimensions, two-dimensional (2D) images
      sliced from any plane in XYZ space can be obtained in shorter acquisition times
      than those required for conventional electron tomography. In this paper, a double
      aberration-corrected SCEM used in annular dark-field mode was used to observe the
      3D structure of SiO(2) hollow spheres fabricated by a carbon template method. The
      double-shell structure of the sample was clearly reflected in both XY- and XZ
      sliced images. However, elongation along the optical axis was still evident in
      the XZ-sliced images even when double aberration correctors were used.
      Application of a deconvolution technique to the experimental XZ-sliced images
      reduced the elongated shell thicknesses of the SiO(2) sphere by 40-50% and the
      selectivity of information at a certain sample depth was also enhanced.
      Subsequently, 3D reconstruction by stacking the deconvoluted slice images
      restored the spherical surface of a SiO(2) sphere.

PMID- 22460389
TI  - Therapeutic effects of intrabone and systemic mesenchymal stem cell cytotherapy
      on myeloma bone disease and tumor growth.
AB  - The cytotherapeutic potential of mesenchymal stem cells (MSCs) has been evaluated
      in various disorders including those involving inflammation, autoimmunity, bone
      regeneration, and cancer. Multiple myeloma (MM) is a systemic malignancy
      associated with induction of osteolytic lesions that often are not repaired even
      after prolonged remission. The aims of this study were to evaluate the effects of
      intrabone and systemic injections of MSCs on MM bone disease, tumor growth, and
      tumor regrowth in the severe combined immunodeficiency (SCID)-rab model and to
      shed light on the exact localization of systemically injected MSCs. Intrabone
      injection of MSCs, but not hematopoietic stem cells, into myelomatous bones
      prevented MM-induced bone disease, promoted bone formation, and inhibited MM
      growth. After remission was induced with melphalan treatment, intrabone-injected
      MSCs promoted bone formation and delayed myeloma cell regrowth in bone. Most
      intrabone or systemically injected MSCs were undetected 2 to 4 weeks after
      injection. The bone-building effects of MSCs were mediated through activation of
      endogenous osteoblasts and suppression of osteoclast activity. Although a single
      intravenous injection of MSCs had no effect on MM, sequential weekly intravenous
      injections of MSCs prevented MM-induced bone disease but had no effect on tumor
      burden. MSCs expressed high levels of anti-inflammatory (eg, HMOX1) and bone
      remodeling (eg, Decorin, CYR61) mediators. In vitro, MSCs promoted osteoblast
      maturation and suppressed osteoclast formation, and these effects were partially
      prevented by blocking decorin. A subset of intravenously or intracardially
      injected MSCs trafficked to myelomatous bone in SCID-rab mice. Although the
      majority of intravenously injected MSCs were trapped in lungs, intracardially
      injected MSCs were mainly localized in draining mesenteric lymph nodes. This
      study shows that exogenous MSCs act as bystander cells to inhibit MM-induced bone
      disease and tumor growth and that systemically injected MSCs are attracted to
      bone by myeloma cells or conditions induced by MM and inhibit bone disease.

PMID- 22460390
TI  - Clinical relevance of quality-of-life data in laryngectomized patients.
AB  - OBJECTIVES/HYPOTHESIS: Statistically significant differences in health-related
      quality of life (HRQL) are not always clinically relevant. It is also plausible
      that patients perceive other changes to be relevant than health professionals do.
      The objective of this study was to find thresholds for HRQL that laryngectomees
      consider to be clinically relevant 1 year after surgery, (i.e., the level of HRQL
      that patients rate as satisfactory). A second aim was to investigate how many
      laryngectomized patients reached those targets. STUDY DESIGN: Multicenter cross
      sectional study. METHODS: A total of 28 patients 1 year following laryngectomy
      and 24 healthcare professionals (HCPs) defined target values for the QLQ-C30 and
      QLQ-H&N35. In another sample of 157 laryngectomized patients 1 year following
      laryngectomy, we determined what percentage of patients reached these thresholds.
      RESULTS: Patients are the most accepting of sensory impairments (56.5), coughing
      (53.6), and dyspnea (44.0), whereas constipation (9.1) and nausea/vomiting (10.7)
      were rated as being the most troublesome symptoms. HCPs assessed more of the
      studied complaints as being tolerable than patients did, especially in
      psychosocial domains. Between 34.5% (senses) and 86.5% (constipation) of the
      reference group hit the predefined targets at different scales. CONCLUSIONS:
      Symptoms caused by disease are easier for patients to live with than more general
      nonspecific symptoms. Taking into account that some adverse effects of disease or
      therapy are partially irreversible, target values additional to changes of HRQL
      can be helpful when interpreting data.

PMID- 22460391
TI  - Ecological approaches to informing public health policy and risk assessments on
      emerging vector-borne zoonoses.
AB  - Pathogens associated with vector-borne zoonoses occur in enzootic cycles within
      nature. They are driven by a combination of vertebrate host and invertebrate
      vector population dynamics, which in turn respond to changes in environmental
      stimuli. Human involvement in these cycles, and hence the occurrence of human
      disease, is often to act as incidental host. From a public health perspective our
      ability to better predict human outbreaks of these diseases and prepare
      intervention and mitigation strategies relies on understanding the natural cycle
      of pathogen transmission. This requires consideration of, for example,
      invertebrate and vertebrate ecology and biology, climatology, land use and
      habitat change. Collectively, these can be referred to as medical entomology and
      medical ecology. This article reviews the importance for inclusion of such
      disciplines when assessing the public health risk from vector-borne zoonoses and
      summarizes the possible future challenges and driving forces for changes in
      vector status and vector-borne zoonoses emergence, with a particular focus on a
      UK and European context.

PMID- 22460392
TI  - Human rhinovirus C: a newly discovered human rhinovirus species.
AB  - Although often ignored, human rhinoviruses (HRVs) are the most frequent causes of
      respiratory tract infections (RTIs). A group of closely related novel
      rhinoviruses have recently been discovered. Based on their unique phylogenetic
      position and distinct genomic features, they are classified as a separate
      species, HRV-C. After their discovery, HRV-C viruses have been detected in
      patients worldwide, with a reported prevalence of 1.4-30.9% among tested
      specimens. This suggests that the species contribute to a significant proportion
      of RTIs that were unrecognized in the past. HRV-C is also the predominant HRV
      species, often with a higher detection rate than that of the two previously known
      species, HRV-A and HRV-B. HRV-C infections appear to peak in fall or winter in
      most temperate or subtropical countries, but may predominate in the rainy season
      in the tropics. In children, HRV-C is often associated with upper RTIs, with
      asthma exacerbation and wheezing episodes being common complications. The virus
      has also been detected in children with bronchitis, bronchiolitis, pneumonia,
      otitis media, sinusitis and systemic infections complicated by pericarditis. As
      for adults, HRV-C has been associated with more severe disease such as pneumonia
      and exacerbation of chronic obstructive pulmonary disease. However, larger
      clinical studies with asymptomatic controls are required to better define the
      significance of HRV-C infection in the adult population. On the basis of VP4
      sequence analysis, a potential distinct subgroup within HRV-C has also been
      identified, although more complete genome sequences are needed to better define
      the genetic diversity of HRV-C.

PMID- 22460393
TI  - Landscape of international event-based biosurveillance.
AB  - Event-based biosurveillance is a scientific discipline in which diverse sources
      of data, many of which are available from the Internet, are characterized
      prospectively to provide information on infectious disease events.
      Biosurveillance complements traditional public health surveillance to provide
      both early warning of infectious disease events and situational awareness. The
      Global Health Security Action Group of the Global Health Security Initiative is
      developing a biosurveillance capability that integrates and leverages component
      systems from member nations. This work discusses these biosurveillance systems
      and identifies needed future studies.

PMID- 22460394
TI  - Road manslaughter-or just the cost of progress?
AB  - Much to the frustration of road safety researchers, practitioners, and advocates,
      road deaths and injuries have not been widely accepted as a major public health
      threat. Currently, road trauma is one of the biggest killers and causes of
      serious and disabling injuries in the world. Although there has been considerable
      research on the causes of road injury and ways of mitigating the problem, there
      is still reluctance to systematically and sufficiently do what can be done to
      reduce this problem globally. This paper takes a historical review of the road
      trauma problem and responses to it. In examining developments in road transport
      and road injury, it is clear that the main impediment to reducing road deaths and
      injury has been a misguided preference of economic advancement over public health
      risk management. It is misguided because road trauma has impeded and does still
      impede the capacity of economies to develop. The challenge for societies now is
      to look at this false dichotomy-that of road development and motorisation versus
      road safety-and begin to make the right choices in favour of human society
      advancement through the development and management of safe road-traffic systems.
      A new 'Safe Systems' approach is emerging in Australia and spreading globally as
      a guiding principle for road safety. The evolution of this approach is traced and
      illustrated in this article. The need for finding ways to engender a stronger
      global political commitment to road safety is demonstrated.

PMID- 22460395
TI  - Risks associated with melamine and related triazine contamination of food.
AB  - Recent adulteration of milk products with melamine (ME) in several countries
      caused adverse health effects and even deaths in infants. Earlier, in 2007,
      contamination of pet food with ME and its related contaminants was associated
      with many clinical cases of canine and feline nephrotoxicity, and in some cases
      mortality. ME is a triazine compound that is often detected with other triazine
      analogs such as cyanuric acid. As is the custom in some livestock operations, the
      contaminated pet food was mixed with feed intended for the swine and poultry
      industry. This practice has raised several questions as to whether ME and its
      related triazines would adversely affect the health of these food animals, and
      whether meat products derived from swine and poultry could contain high-enough
      levels of these contaminants to warrant public health concern. Data for this
      review article were obtained from recent research efforts in our laboratory, peer
      reviewed publications cited in PubMed, and information available at USDA, US FDA,
      and WHO websites. The primary issues discussed are related to (1) the chemistry
      and interactions between ME and its triazine analogs; (2) reported animal and
      human exposures with possible pathways through which ME can enter the human food
      chain; (3) mammalian toxicology; (4) comparative pharmacokinetics (PK) and
      modeling strategies used to predict residue levels; and (5) emerging issues and
      management strategies.

PMID- 22460396
TI  - Innovation in observation: a vision for early outbreak detection.
AB  - The emergence of new infections and resurgence of old onesFhealth threats
      stemming from environmental contamination or purposeful acts of bioterrorismFcall
      for a worldwide effort in improving early outbreak detection, with the goal of
      ameliorating current and future risks. In some cases, the problem of outbreak
      detection is logistically straightforward and mathematically easy: a single case
      of a disease of great concern can constitute an outbreak. However, for the vast
      majority of maladies, a simple analytical solution does not exist. Furthermore,
      each step in developing reliable, sensitive, effective surveillance systems
      demonstrates enormous complexities in the transmission, manifestation, detection,
      and control of emerging health threats. In this communication, we explore
      potential future innovations in early outbreak detection systems that can
      overcome the pitfalls of current surveillance. We believe that modern advances in
      assembling data, techniques for collating and processing information, and
      technology that enables integrated analysis will facilitate a new paradigm in
      outbreak definition and detection. We anticipate that moving forward in this
      direction will provide the highly desired sensitivity and specificity in early
      detection required to meet the emerging challenges of global disease
      surveillance.

PMID- 22460398
TI  - Current research on public perceptions of nanotechnology.
AB  - This review explores research on public perceptions of nanotechnology. It
      highlights a recurring emphasis on some researchers' expectations that there will
      be a meaningful relationship between awareness of nanotechnology and positive
      views about nanotechnology. The review, however, also notes that this emphasis is
      tacitly and explicitly rejected by a range of multivariate studies that emphasize
      the key roles of non-awareness variables, such as, trust, general views about
      science, and overall worldview. The review concludes with a discussion of likely
      future research directions, including the expectation that social scientists will
      continue to focus on nanotechnology as a unique opportunity to study how
      individuals assess risk in the context of relatively low levels of knowledge.

PMID- 22460397
TI  - Emerging viral threats in Gabon: health capacities and response to the risk of
      emerging zoonotic diseases in Central Africa.
AB  - Emerging infectious diseases (EID) are currently the major threat to public
      health worldwide and most EID events have involved zoonotic infectious agents.
      Central Africa in general and Gabon in particular are privileged areas for the
      emergence of zoonotic EIDs. Indeed, human incursions in Gabonese forests for
      exploitation purposes lead to intensified contacts between humans and wildlife
      thus generating an increased risk of emergence of zoonotic diseases. In Gabon, 51
      endemic or potential endemic viral infectious diseases have been reported. Among
      them, 22 are of zoonotic origin and involve 12 families of viruses. The most
      notorious are dengue, yellow fever, ebola, marburg, Rift Valley fever and
      chikungunya viruses. Potential EID due to wildlife in Gabon are thereby plentiful
      and need to be inventoried. The Gabonese Public Health system covers
      geographically most of the country allowing a good access to sanitary information
      and efficient monitoring of emerging diseases. However, access to treatment and
      prevention is better in urban areas where medical structures are more developed
      and financial means are concentrated even though the population is equally
      distributed between urban and rural areas. In spite of this, Gabon could be a
      good field for investigating the emergence or re-emergence of zoonotic EID.
      Indeed Gabonese health research structures such as CIRMF, advantageously located,
      offer high quality researchers and facilities that study pathogens and wildlife
      ecology, aiming toward a better understanding of the contact and transmission
      mechanisms of new pathogens from wildlife to human, the emergence of zoonotic EID
      and the breaking of species barriers by pathogens.

PMID- 22460399
TI  - Posterior spinal fusion from T2 to the sacrum for the management of major
      deformities in patients with Parkinson disease: a retrospective review with
      analysis of complications.
AB  - STUDY DESIGN: Description of the surgical management of major spinal deformities
      in patients with Parkinson disease (PD). OBJECTIVE: To evaluate the effectiveness
      of the construct, the incidence and types of complications, and patient
      satisfaction. SUMMARY OF BACKGROUND DATA: The association of degenerative,
      neuromuscular, and osteoporotic diseases in PD can lead to major complications
      after spine surgery. We treated PD patients with major spinal deformities by a
      posterior-only approach for spinal fusion from T2 to the sacrum. METHODS: : This
      retrospective study reviews 12 consecutive patients with PD undergoing this
      surgery in a 2-year span at a single institution. Radiographs were taken with the
      EOS low-dose system (EOS Imaging, Paris, France) before and 3 months after
      surgery and at the last follow-up visit and were evaluated by a spine surgeon not
      involved in the surgery. Complications were analyzed. The functional outcome was
      assessed with the SRS-30 questionnaire. RESULTS: The patients' mean age was 68+/
      6.2 years, the mean duration of PD 10+/-4.9 years, and the mean follow-up 32.8+/
      6.9 months. Six patients had first surgeries, and 6 revisions. Statistically
      significant improvement was observed in all patients in the frontal and the
      sagittal planes after surgery. The sagittal vertical axis improved from 15.2+/
      9.3 cm preoperatively to 0.5+/-3.2 cm at the last follow-up. Six patients had
      revision, 3 times for instrumentation failure, twice for proximal junctional
      kyphosis at T1-T2, and once for an epidural hematoma. The SRS-30 questionnaire
      indicated strong patient satisfaction, with 11 patients who would have the same
      procedure again if they had the same condition. CONCLUSIONS: This is the first
      reported series of PD patients undergoing posterior spinal fusion from T2 to the
      sacrum for major deformities. This study indicates that good correction of
      sagittal and frontal balance enables good clinical and radiologic results that
      remain stable over time even when complications occur.

PMID- 22460400
TI  - Risk factors for adjacent segment disease after posterior lumbar interbody fusion
      and efficacy of simultaneous decompression surgery for symptomatic adjacent
      segment disease.
AB  - STUDY DESIGN: A retrospective study. SUMMARY OF BACKGROUND DATA: Posterior lumbar
      interbody fusion (PLIF) increases mechanical stress and can cause degenerative
      changes at the adjacent segment. However, the precise causes of adjacent segment
      disease (ASD) after PLIF are not known, and it is unclear whether simultaneous
      decompression surgery for symptomatic ASD is effective. OBJECTIVE: To study,
      radiographically and symptomatically, the risk factors for adjacent segment
      disease (ASD) in the lumbar spine after L4/5 PLIF and to examine whether
      decompression surgery for the adjacent segment (L3/4) reduces the occurrence of
      symptomatic ASD. METHODS: Fifty-four patients who underwent L4/5 PLIF for L4
      degenerative spondylolisthesis and could be followed up for at least 2 years were
      included. Of these, 37 were treated simultaneously with decompression surgery at
      L3/4. We measured radiographic changes and assessed symptoms from the cranial
      adjacent segment. RESULTS: Thirty-one patients (57.4%) met radiologic criteria
      for ASD. The length of follow-up (P=0.004) and simultaneous decompression surgery
      at L3/4 (P=0.009) were statistically significant factors for radiologic diagnosis
      of ASD. Seven patients (13.0%) had symptomatic ASD: 6 in the decompression group
      (16.2%) and 1 in the PLIF-only group (5.9%). Simultaneous decompression surgery
      did not reduce the incidence of symptomatic ASD (P=0.256). Local lordosis at the
      fused segment (P=0.005) and the sagittal angle of the facet joint at L3/4
      (P=0.024) were statistically significant predictors of symptomatic ASD, which was
      accompanied by postoperative anterior listhesis above the fused segment (S group,
      8.4%+/-8.0%; nonsymptomatic group: -0.7%+/-5.0%, P=0.024). CONCLUSIONS: Patients
      whose facet joint at the adjacent segment had a more sagittal orientation had
      postoperative anterior listhesis, which caused symptomatic ASD. Simultaneous
      decompression surgery without fusion at the adjacent level was not effective for
      these patients, but rather, there was a possibility that it induced symptomatic
      ASD.

PMID- 22460401
TI  - An optimized video system for augmented reality in endodontics: a feasibility
      study.
AB  - OBJECTIVES: We propose an augmented reality system for the reliable detection of
      root canals in video sequences based on a k-nearest neighbor color classification
      and introduce a simple geometric criterion for teeth. MATERIAL AND METHODS: The
      new software was implemented using C++, Qt, and the image processing library
      OpenCV. Teeth are detected in video images to restrict the segmentation of the
      root canal orifices by using a k-nearest neighbor algorithm. The location of the
      root canal orifices were determined using Euclidean distance-based image
      segmentation. A set of 126 human teeth with known and verified locations of the
      root canal orifices was used for evaluation. RESULTS: The software detects root
      canals orifices for automatic classification of the teeth in video images and
      stores location and size of the found structures. Overall 287 of 305 root canals
      were correctly detected. The overall sensitivity was about 94 %. Classification
      accuracy for molars ranged from 65.0 to 81.2 % and from 85.7 to 96.7 % for
      premolars. CONCLUSION: The realized software shows that observations made in
      anatomical studies can be exploited to automate real-time detection of root canal
      orifices and tooth classification with a software system. CLINICAL RELEVANCE:
      Automatic storage of location, size, and orientation of the found structures with
      this software can be used for future anatomical studies. Thus, statistical tables
      with canal locations will be derived, which can improve anatomical knowledge of
      the teeth to alleviate root canal detection in the future. For this purpose the
      software is freely available at: http://www.dental-imaging.zahnmedizin.uni
      mainz.de/.

PMID- 22460402
TI  - Regional factors rather than forest type drive the community structure of soil
      living oribatid mites (Acari, Oribatida).
AB  - Most European forests are managed by humans. However, the manner and intensity of
      management vary. While the effect of forest management on above-ground
      communities has been investigated in detail, effects on the below-ground fauna
      remain poorly understood. Oribatid mites are abundant microarthropods in forest
      soil and important decomposers in terrestrial ecosystems. Here, we investigated
      the effect of four forest types (i.e., managed coniferous forests; 30 and 70
      years old managed beech forests; natural beech forests) on the density, diversity
      and community structure of oribatid mites (Acari). The study was replicated at
      three regions in Germany: the Swabian Alb, the Hainich and the Schorfheide. To
      relate changes in oribatid mite community structure to environmental factors,
      litter mass, pH, C and N content of litter, fine roots and C content of soil were
      measured. Density of oribatid mites was highest in the coniferous forests and
      decreased in the order 30 years old, 70 years old, and natural beech forests.
      Mass of the litter layer and density of oribatid mites were strongly correlated
      indicating that the litter layer is an important factor regulating oribatid mite
      densities. Diversity of oribatid mites was little affected by forest type
      indicating that they harbor similar numbers of niches. Species composition
      differed between the forest types, suggesting different types of niches. The
      community structure of oribatid mites differed more strongly between the three
      regions than between the forest types indicating that regional factors are more
      important than effects associated with forest type.

PMID- 22460404
TI  - Brief communication: Short- and long-term in vivo human buccal-dental microwear
      turnover.
AB  - Buccal-dental microwear depends on the abrasive content of chewed foodstuffs and
      can reveal long-term dietary trends in human populations. However, in vivo
      experimental analyses of buccal microwear formation processes are scarce. Here,
      we report the effects of an abrasive diet on microwear rates in two adult
      volunteers at intervals of 8 days over a period of 1 month and document long-term
      turnover over 5 consecutive years in the same subjects under an ad libitum
      Mediterranean diet. Buccal microwear was analyzed on mandibular first molars
      using high-resolution replicas and scanning electron microscopy. Microwear
      turnover was assessed by recording the scratches lost and gained at each time
      point. Our results indicate that scratch formation on enamel surfaces increased
      with a highly abrasive diet compared to both pre-test and post-test ad libitum
      dietary controls. In the long-term analysis, scratch turnover was higher than
      expected, but no significant long-term trends in microwear density or length were
      observed, because microwear formation was compensated by scratch disappearance.
      Our results confirm that buccal microwear patterns on mandibular molars show a
      dynamic formation process directly related to the chewing of abrasive particles
      along with ingested food. In addition, the observed long-term stability of buccal
      microwear patterns makes them a reliable indicator of overall dietary habits.

PMID- 22460403
TI  - Strain and its correlates among carers of people with dementia in low-income and
      middle-income countries. A 10/66 Dementia Research Group population-based survey.
AB  - OBJECTIVES: In a multi-site population-based study in several middle-income
      countries, we aimed to investigate relative contributions of care arrangements
      and characteristics of carers and care recipients to strain among carers of
      people with dementia. Based on previous research, hypotheses focused on carer
      sex, care inputs, behavioural and psychological symptoms (BPSD) and socioeconomic
      status, together with potential buffering effects of informal support and
      employing paid carers. METHODS: In population-based catchment area surveys in 11
      sites in Latin America, India and China, we analysed data collected from people
      with dementia and care needs, and their carers. Carer strain was assessed with
      the Zarit Burden Interview. RESULTS: With 673 care recipient/carer dyads
      interviewed (99% of those eligible), mean Zarit Burden Interview scores ranged
      between 17.1 and 27.9 by site. Women carers reported more strain than men. The
      most substantial correlates of carer strain were primary stressors BPSD, dementia
      severity, needs for care and time spent caring. Socioeconomic status was not
      associated with carer strain. Those cutting back on work experienced higher
      strain. There was tentative evidence for a protective effect of having additional
      informal or paid support. CONCLUSIONS: Our findings underline the global impact
      of caring for a person with dementia and support the need for scaling up carer
      support, education and training. That giving up work to care was prevalent and
      associated with substantial increased strain emphasizes the economic impact of
      caring on the household. Carer benefits, disability benefits for people with
      dementia and respite care should all be considered.

PMID- 22460405
TI  - Facile synthesis of pendant- and alpha,omega-chain-end-functionalized
      polycarbonates via immortal polymerization by using a salan lutetium alkyl
      precursor.
AB  - A highly efficient strategy for synthesizing functionalized polycarbonates was
      established by employing a rare-earth metal catalyst.

PMID- 22460406
TI  - On mosaics and consensus: Gaudi, Brazil and rheumatoid arthritis.

PMID- 22460407
TI  - 2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid
      arthritis.
AB  - OBJECTIVE: To elaborate recommendations for the treatment of rheumatoid arthritis
      in Brazil. METHOD: Literature review with articles' selection based on evidence
      and the expert opinion of the Rheumatoid Arthritis Committee of the Brazilian
      Society of Rheumatology. RESULTS AND CONCLUSIONS: 1) The therapeutic decision
      should be shared with the patient; 2) immediately after the diagnosis, a disease
      modifying antirheumatic drug (DMARD) should be prescribed, and the treatment
      adjusted to achieve remission; 3) treatment should be conducted by a
      rheumatologist; 4) the initial treatment includes synthetic DMARDs; 5)
      methotrexate is the drug of choice; 6) patients who fail to respond after two
      schedules of synthetic DMARDs should be assessed for the use of biologic DMARDs;
      7) exceptionally, biologic DMARDs can be considered earlier; 8) anti-TNF agents
      are preferentially recommended as the initial biologic therapy; 9) after
      therapeutic failure of a first biologic DMARD, other biologics can be used; 10)
      cyclophosphamide and azathioprine can be used in severe extra-articular
      manifestations; 11) oral corticoid is recommended at low doses and for short
      periods of time; 12) non-steroidal anti-inflammatory drugs should always be
      prescribed in association with a DMARD; 13) clinical assessments should be
      performed on a monthly basis at the beginning of treatment; 14) physical therapy,
      rehabilitation, and occupational therapy are indicated; 15) surgical treatment is
      recommended to correct sequelae; 16) alternative therapy does not replace
      traditional therapy; 17) family planning is recommended; 18) the active search
      and management of comorbidities are recommended; 19) the patient's vaccination
      status should be recorded and updated; 20) endemic-epidemic transmissible
      diseases should be investigated and treated.

PMID- 22460408
TI  - Neuropsychological assessment of cognitive disorders in patients with
      fibromyalgia, rheumatoid arthritis, and systemic lupus erythematosus.
AB  - INTRODUCTION: This study assesses the possible existence of cognitive disorder
      associated with chronic diseases [fibromyalgia (FM), rheumatoid arthritis (RA)
      and lupus (SLE)], and the influence of the variables age, educational level and
      psychiatric symptoms on those disorders. MATERIALS AND METHODS: The patients were
      referred by the Rheumatology Outpatient Clinic of the Hospital Universitario de
      Brasilia (HUB), with ages ranging from 30 to 80 years, and were divided into the
      following three groups: FM, 13 patients; RA, 13 patients; and SLE, 11 patients.
      Their performance in the neuropsychological tests of memory, language, executive
      functions and neuropsychiatric inventory was assessed considering their type of
      chronic disease, educational level and age. In addition, the cutoff points of
      cognitive normality of population samples were compared with the patients'
      performances. RESULTS: The cognitive disorders were shown to be associated with
      the three diseases studied, but with significant differences between them.
      CONCLUSION: The variables studied (low educational level and advanced age) were
      associated with various degrees of impairment in the different cognitive
      functions in the three pathological groups. However, FM and SLE groups showed
      significantly higher means of the neuropsychiatric symptoms of anxiety,
      irritability and hallucinations than the RA group in the neuropsychiatric
      inventory.

PMID- 22460409
TI  - Work and power of the knee flexor and extensor muscles in patients with
      osteoarthritis and after total knee arthroplasty.
AB  - INTRODUCTION: The inflammatory manifestations of knee osteoarthritis (OA) lead to
      muscle inhibition and hypotrophy, resulting in a reduction in total muscle work
      and muscle power. Total knee arthroplasty (TKA) is the most adequate surgery for
      the treatment of advanced OA. However, its effects on muscle functional behavior
      have not been well understood. OBJECTIVE: To compare the total work and power of
      the knee flexor and extensor muscles in patients with OA (20) and in patients
      post-TKA (12) at two angular velocities (60o/sec and 240o/sec). METHODS: An
      isokinetic Biodex dynamometer was used to assess muscle power and total work
      during isokinetic contractions. Two-way ANOVA for repeated measures was used to
      compare total muscle work and muscle power between the groups (SPSS software,
      version 13.0; significance level, P < 0.05). RESULTS: There was no difference
      between the OA and TKA groups for the total work of both knee extensors and
      flexors at the two angular velocities (P > 0.05). In addition, no difference was
      observed in the muscle power of the knee extensors and flexors (P > 0.05).
      CONCLUSION: Total work and power were similar in the OA and TKA groups,
      suggesting that TKA did not improve functional capacity, which was similar in
      both groups.

PMID- 22460411
TI  - Use of high-voltage cathodic current for pain in experimental nerve compression.
AB  - OBJECTIVE: To assess the effect of high-voltage cathodic current on pain from a
      sciatica experimental model. METHODS: A total of 16 male Wistar rats were
      submitted to the sciatica experimental model in the right hind paw. They were
      divided into sham group (GS) and group treated with cathodic current (GP-) for 20
      min/daily, for 10 days). The model of sciatic compression was performed with a
      4.0-chromic catgut thread tie in four points of the sciatic nerve. Assessment of
      nociception was performed by measuring the time during which the animal held its
      hind paw in a guarded position (THHP) and the pressure withdrawal threshold, by
      use of a digital electronic analgesymeter. Data collection was carried out before
      the sciatica experimental model (AS1), three days after compression (before, AS2,
      and after treatment, AS3), and five and 10 days after treatment (AS4 and AS5,
      respectively). RESULTS: According to the functional disability test, both groups
      showed an increase in nociception, with no reduction at any assessment time.
      Submitted to pressure, however, GS showed a reduction in the hind paw withdrawal
      threshold at all assessment times, while GP- showed a reduction in the hind paw
      withdrawal threshold only initially - at AS5, the threshold was restored.
      CONCLUSION: No change in nociception was observed on functional assessment;
      however, on pressure hind paw withdrawal assessment, the treatment with cathodic
      current showed to be effective with the summation of therapies.

PMID- 22460410
TI  - Profile of users of anticytokines offered by the health care system in the state
      of Parana for the treatment of rheumatoid arthritis.
AB  - INTRODUCTION: The Brazilian Unified Health Care System (SUS) offers treatment for
      patients with RA through federal funding (Ministry of Health) and state co
      financing. The Clinical Protocol and Therapeutic Guidelines for the treatment of
      rheumatoid arthritis describe the therapeutic regimen for the disease, including
      the anticytokines adalimumab, etanercept or infliximab. OBJECTIVES: The aim of
      this study was to evaluate the profile of registered users of those
      anticytokines, biologics registered in the Information System of the
      Pharmaceutical Assistance Specialized Division, managed by the Parana State Drug
      Center. METHODS: A cross-sectional study regarding data from March 2010 was
      conducted. Based on dispensation data, information regarding the following
      variables were collected: age; gender; regional health care centers;
      International Classification of Diseases (ICD); and drug dispensed. In addition,
      the monthly cost with anticytokines for the SUS was calculated. RESULTS: In the
      state of Parana, 923 patients on anticytokines were identified, 40%, 44% and 16%
      of whom receiving adalimumab, etanercept and infliximab, respectively. This
      generated a monthly cost of R$3,403,195.59. Regarding the ICD, the distribution
      of patients was as follows: 55% had ICD M05.8; 27%, ICD M06.0; 9%, ICD M6.8; 8%,
      ICD M5.0; and 1% had other ICDs related to the disease. The regional health care
      centers of the state of Parana with the largest number of patients on
      anticytokines were in the following municipalities: Ponta Grossa; Cornelio
      Procopio; Londrina; Cianorte; Maringa; Irati; and Campo Mourao. CONCLUSION: This
      study assessed the distribution and profile of users of anticytokines for the
      rheumatoid arthritis treatment covered by the SUS in the state of Parana, in
      March 2010.

PMID- 22460412
TI  - Laryngeal and tracheobronchial involvement in Wegener's granulomatosis.
AB  - INTRODUCTION: Wegener's granulomatosis (WG) is a form of systemic vasculitis that
      involves primarily the upper and lower airways and the kidneys. The most frequent
      airway manifestations include subglottic stenosis and inflammation, and tracheal
      and bronchial stenoses. The endoscopic visualization of the airways is the best
      tool for assessing, diagnosing and managing those changes. OBJECTIVES: To
      describe the endoscopic abnormalities found in the airway mucosa of a group of
      patients with WG undergoing bronchoscopy at Hospital das Clinicas of the
      Faculdade de Medicina, Universidade de Sao Paulo (HC-FMUSP), and to report the
      therapeutic bronchoscopic interventions used in some cases. METHODS: The study
      assessed 15 patients diagnosed with GW from the Vasculitis Outpatient Clinic of
      the Department of Pulmonology, HC-FMUSP, referred for bronchoscopy at the Service
      of Respiratory Endoscopy, HC-FMUSP, from 2003 to 2007. RESULTS: Fifteen patients
      were studied [11 females (73.33%)]; mean age, 34 +/- 11.5 years. Airway changes
      were found in 80% of the patients, and the most frequent endoscopic finding was
      subglottic stenosis (n = 6). Therapeutic bronchoscopy was performed in three
      patients with subglottic stenosis and in other three patients with bronchial
      stenosis, all showing good results. CONCLUSION: Bronchoscopy allows for
      diagnosing, monitoring, and treating the airway lesions in WG, being a minimally
      invasive therapeutic option in selected cases.

PMID- 22460413
TI  - Rheumatic fever presentation and outcome: a case-series report.
AB  - OBJECTIVE: To assess the clinical characteristics and outcome of a rheumatic
      fever case-series from a referral hospital over the last 20 years. PATIENTS AND
      METHODS: Patients under the age of 18 years, diagnosed with rheumatic fever
      between 1986 and 2007 were retrospectively assessed to estimate the carditis and
      relapse rates, by use of descriptive and survival analysis. RESULTS: Of 178 cases
      identified, 134 were included. During the acute phase, 66.4% had polyarthritis,
      56.8% had carditis, 28.6% had chorea, 1.5% had subcutaneous nodules, and 1.5% had
      erythema marginatum. The association of carditis and arthritis occurred in 40%.
      Carditis and chorea were more frequent among female gender. High antistreptolysin
      O titres were found in 58.3%, and family history of rheumatic fever, in 14.5%.
      Mean follow-up was 6.8 years (1.1 to 16.9). Relapse was observed in 15%, hospital
      admissions in 27.6%, and follow-up discontinuation in 47.4% after a mean of 5.1
      years. Carditis and relapse probabilities were 17.5% and 13.2%, respectively,
      five years after the initial attack. CONCLUSION: The risk of carditis and relapse
      of rheumatic fever was higher within the first five years. Follow-up
      discontinuation was frequent, pointing to the need of measures to improve
      adherence to prophylaxis and follow-up.

PMID- 22460414
TI  - Mechanisms of muscle wasting in sarcopenia.
AB  - Approximately 66% of the patients with rheumatoid arthritis (RA) have significant
      loss of cell mass (rheumatoid cachexia), mainly of skeletal muscle (rheumatoid
      sarcopenia). Sarcopenia is defined as muscle wasting associated with functional
      impairment. Patients with RA possess significant reduction in muscle strength,
      caused by muscle protein wasting, and loss of functionality. Various conditions
      leading to muscle wasting involve different pathways of intracellular signaling
      that trigger: (i) programmed cell death (apoptosis); (ii) increased protein
      degradation through autophagy, calcium-dependent proteases (calpains and
      caspases), and proteasome system; (iii) decreased satellite cell activation,
      responsible for muscle regeneration. This article aimed at reviewing these
      general mechanisms of sarcopenia and their involvement in RA. Greater knowledge
      of these mechanisms may lead to the development of innovative therapies to this
      important comorbidity.

PMID- 22460415
TI  - Bisphosphonate-related osteonecrosis of the jaw.
AB  - Bisphosphonates (BPs) have been used for the management of bone metabolic
      diseases. Currently their therapeutic use has increased, as also have their
      adverse effects, one of the most important being the bisphosphonate-related
      osteonecrosis of the jaw (BRONJ), a complication of difficult treatment and
      solution. Until now, the physiopathology of BRONJ remains unclear, and its
      treatment is uncertain. Although the literature provides several treatment
      options, there is no defined protocol. We present a review about BRONJ, focusing
      on its pathogenesis and its reported forms of treatment.

PMID- 22460416
TI  - Possible role of adipokines in systemic lupus erythematosus and rheumatoid
      arthritis.
AB  - In recent years, mediators synthesized in the adipose tissue, the so-called
      adipokines, have been described. They have a hormonal action, regulating appetite
      and glucose metabolism, but also act as cytokines with effects on the immune
      system, including effects on autoimmunity. The most important adipokines are
      leptin, adiponectin, resistin and visfatin, and some of them have been assessed
      in autoimmune rheumatic diseases, especially systemic lupus erythematosus (SLE)
      and rheumatoid arthritis (RA). Studies have shown high levels of leptin and
      adiponectin in SLE, but correlation with disease activity is questionable. In RA,
      studies have also reported increased levels of leptin and adiponectin, and
      correlation with disease activity and joint erosion, but the results are
      conflicting. This review describes the role of leptin and adiponectin on the
      immune system, as well as on SLE and RA.

PMID- 22460417
TI  - Eritema elevatum diutinum as a differential diagnosis of rheumatic diseases: case
      report.
AB  - Erythema elevatum diutinum is a chronic and rare cutaneous leukocytoclastic
      vasculitis, characterized by red, purple and yellow papules, plaques and nodules,
      distributed symmetrically on the extensor surfaces of the limbs. It is associated
      with several autoimmune, neoplastic and infectious processes, mainly
      hematological malignancies in about 30% of the cases. Joint pain and arthritis
      are frequent symptoms, affecting approximately 40% of the patients, indicating
      the need for its inclusion in the differential diagnosis of rheumatic diseases,
      chiefly the other presentations of leukocytoclastic vasculitis, which are
      characterized by the combination of rheumatic manifestations and peculiar
      cutaneous lesions. We report the case of an 18-year-old female patient who
      developed erythema elevatum diutinum and whose diagnosis was based on the
      morphologic characteristics, the distribution pattern of the cutaneous lesions
      and the histopathological findings of leukocytoclastic vasculitis. The major
      systemic symptom was severe arthritis.

PMID- 22460418
TI  - Mycophenolate mofetil in primary Sjogren's syndrome: a treatment option for
      agranulocytosis.
AB  - The Sjogren's syndrome (SS) is an autoimmune disease characterized by a
      lymphocytic infiltration of salivary and lacrimal glands. Hematological
      manifestations of primary SS (pSS) usually consist of mild anemia,
      thrombocytopenia, moderate neutropenia, and lymphopenia. Agranulocytosis is
      rarely reported and usually responds to immunosuppression. We report the case of
      a pSS patient who presented with refractory agranulocytosis. Bone marrow biopsy
      disclosed a hypocellular bone marrow with normal maturation of the granulocytic
      series. The patient was successively treated with high-dose prednisone,
      granulocyte-macrophage colony stimulation factor, and cyclosporine, with no
      hematological response. Mycophenolate mofetil (MMF) was initiated and after two
      months there was a rise on the white blood cell count. After one year of follow
      up, she had neither further neutropenia episodes, nor infectious complications.
      We conclude that, in pSS refractory agranulocytosis, MMF can be an effective and
      well-tolerated treatment option.

PMID- 22460419
TI  - Nazi past and changes in disease names: the Wegener's disease case.

PMID- 22460420
TI  - Functional analysis of two chitinase genes during the pupation and eclosion
      stages of the beet armyworm Spodoptera exigua by RNA interference.
AB  - Insect chitinases are a multigene family that is encoded by a rather large and
      diverse group of genes. The main function of chitinases is to digest the chitin
      contained in tissues such as the cuticles and gut lining during molting. In this
      study, we examined the role of a chitinase (SeChi) and a bacterial type chitinase
      (SeChi-h) during the pupation and eclosion stages of Spodoptera exigua. First,
      efficient silencing of the SeChi and SeChi-h genes through specific double
      stranded RNA (dsRNA) injection led to a significant reduction in the mRNA levels
      of SeChi and SeChi-h. Additionally, different phenotypic defects were observed at
      the pupal and adult stages after injection of the SeChi and SeChi-h dsRNAs. After
      injecting SeChi dsRNA in the pupal stage, the cuticle of the head split open and
      the pupal cuticle was visible under the old larval cuticle. However, after
      injecting the SeChi-h dsRNA, animals died without exhibiting any special
      phenotypes. At the adult death stage, animals injected with dsSeChi could not
      shed their pupal shell completely, and their old cuticles remained attached to
      their head or chest. However, the main lethal phenotype was that insects did not
      emerge after dsSeChi-h injection. Additionally, the average survival rates of S.
      exigua were 52.02% and 40.38% at the pupal and adult stages, respectively, after
      injection with SeChi dsRNA. For the insects injected with SeChi-h dsRNA, the
      survival rates were 72.38% and 48.52%, respectively. These results suggest that
      SeChi and SeChi-h may have different biologic functions during the pupal-adult
      molting.

PMID- 22460422
TI  - Evidence-based research on traditional Japanese medicine, Kampo, in treatment of
      gastrointestinal cancer in Japan.
AB  - Gastrointestinal cancer is a great threat to human health in Japan. Conventional
      anticancer therapies including surgery, radiation, and chemotherapy are the main
      strategies and play important roles in curing this disease or extending the life
      of patients with these cancers. On the other hand, patients undergo great
      suffering induced by these treatments. Kampo, the Japanese traditional medicine,
      has been used in clinics to reduce side effects and to improve the quality of
      life of gastrointestinal cancer patients in Japan. In order to testify to the
      efficacy and safety of these Kampo medicines and to clarify the underlying
      mechanisms, a number of clinical and basic studies were implemented in the past
      several decades. These studies suggested the benefits of Kampo medicine as an
      adjuvant to conventional anti-cancer therapies in treating gastrointestinal
      cancer. Since the safety and efficacy as well as quality control of traditional
      medicine have long been focused worldwide, the development course of Kampo
      medicine may provide reference to other countries in the world.

PMID- 22460421
TI  - Health-related quality of life in nonsplenectomized immune thrombocytopenia
      patients receiving romiplostim or medical standard of care.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet
      destruction and insufficient platelet production. The resulting thrombocytopenia
      reduces patient health-related quality of life (HRQOL). In a randomized, open
      label, 52-week study of non-splenectomized ITP patients treated with romiplostim
      or medical standard of care (SOC), patients completed the 10-scale ITP-patient
      assessment questionnaire (PAQ) at the start of the study and after 12, 24, 36,
      48,and 52 weeks of treatment. HRQOL changes were examined for all patients in
      both treatment groups and by responder status, splenectomy status, and after the
      use of rituximab. Patients in both groups showed marked increases in all HRQOL
      scales over 52 weeks of treatment.These change scores exceeded the minimally
      important difference values (a measure of clinical relevance) for most of these
      scales,especially in responders to treatment. Compared with baseline,patients
      receiving romiplostim showed statistically significant improvements compared to
      SOC over 52 weeks for the ITP-PAQ scales of Symptoms, Bother, Activity,
      Psychological Health, Fear, Overall QOL,and Social QOL. Overall, treatment of ITP
      was associated with improvement in HRQOL. Patients receiving romiplostim had
      greater HRQOL improvements than those receiving SOC, but the magnitude ofthe
      difference is of uncertain clinical benefit.

PMID- 22460423
TI  - Synthesis of solasodine glycoside derivatives and evaluation of their cytotoxic
      effects on human cancer cells.
AB  - Solasodine glycosides, such as solamargine, have been proved to be very important
      anti-cancer agents. In order to discover more potent cytotoxic agents and explore
      the preliminary structure activity relationship, a new series of solasodine
      glycosides 2-9 were synthesized via a transglycosylation strategy, and their
      cytotoxic activity against a panel of human cancer cell lines (MCF-7, KB, K562,
      and PC3 cells) were evaluated by MTT assays. The results indicated that compounds
      2, 8, and 9 with the substitute moiety of rhamnose, 2-hydroxyethoxymethyl, and
      1,3-dihydroxypropan-2-yloxy-methyl, respectively, exhibited quite strong
      anticancer activity. The underlying mechanism tests demonstrated that these
      compounds could induce apoptosis detected by DAPI staining, and Annexin V and
      propidium iodide binding. Cell cycle analysis indicated that the cancer cells
      were predominantly arrested at the G2/M phase when exposure to these compounds
      was examined by flow cytometry. These compounds may serve as lead candidates in
      the development of novel chemotherapeutics for cancer treatment.

PMID- 22460424
TI  - Identification and evaluation of agents isolated from traditionally used herbs
      against Ophiophagus hannah venom.
AB  - The aim of this study was firstly to identify active molecules in herbs, that are
      traditionally used for the treatment of snake bite, such as Curcuma antinaia,
      Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium;
      secondly to test similar structurally related molecules and finally to prepare
      and evaluate an efficient formulation against Ophiophagus hannah venom
      intoxification. Three labdane based compounds, including labdane dialdehyde,
      labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy
      11,12-didehydroandrographolide and parthenolide were isolated by column
      chromatography and characterised. Using the isolated rat phrenic nerve
      hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated
      compounds and prepared formulations were measured in vitro on the inhibition of
      the neuromuscular transmission. Inhibition on muscle contraction, produced by the
      5 MUg/mL venom, was reversed by test agents in organ bath preparations. A labdane
      trialdehyde, isolated from C. contravenenum, was identified as the best
      antagonising agent in the low micromolar range. Tests on formulations of the most
      potent C. contravenenum extract showed, that the suppository with witepsol H15
      was an effective medicine against O. hannah venom. This study elucidated the
      active compounds, accounting for the antivenin activity of traditionally used
      herbs and suggested the most suitable formulation, which may help to develop
      potent medicines for the treatment of snake bite in the future.

PMID- 22460425
TI  - LKB1, TP16, EGFR, and KRAS somatic mutations in lung adenocarcinomas from a Chiba
      Prefecture, Japan cohort.
AB  - The discovery of somatic mutations in cancer-related genes has been applied to
      understand the genetic basis of cancer. Here we report somatic mutations of two
      tumor suppressor genes: LKB1 (exons 1, 4, and 8) and TP16 (CDKN2A) (exons 1 and
      2); and two oncogenes: epidermal growth factor receptor EGFR (exons 18-21) and
      KRAS (exon 2) in 97 lung adenocarcinoma tissues in a cohort from the Kujukuri
      coast area of Chiba, Japan. In the LKB1 gene, only F354L substitutions were
      observed in 14 of the 97 tissue samples (14.4%). In the TP16 gene, only two
      deletions were observed in contrast to previous reports. On the other hand, the
      EGFR gene was highly mutated (38.1%) and mainly L858R substitutions occurred
      (23.7%) as well as insertions and deletions. In the KRAS gene, 10 substitutions
      at codon 12 were observed (10.3%). Co-occurrence of EGFR and KRAS somatic
      mutations was identified in one patient, those of EGFR and LKB1 were in three
      patients, and those of KRAS and LKB1 were in four patients. The lower rates of
      LKB1, TP16, and KRAS somatic mutations in lung adenocarcinomas are characteristic
      of the Kujukuri cohort as compared to Caucasians.

PMID- 22460426
TI  - Inhibition of morphine tolerance is mediated by painful stimuli via central
      mechanisms.
AB  - Tolerance to morphine analgesia following repeated administration disturbs the
      continuation of opioid therapy for severe pain. Emerging evidence suggests that
      the development of morphine tolerance may be antagonized by painful stimuli. To
      clarify the detailed mechanisms of these phenomena, we examined the effects of
      several pain stimuli on morphine-induced tolerance. Subcutaneous (s.c.) injection
      of morphine (10 mg/kg) produced an analgesic effect, which was evaluated by tail
      pinch test. Morphine-induced analgesia was diminished by repeated administration
      of morphine (10 mg/kg, s.c.) once a day for 5 days, demonstrating the development
      of tolerance. Morphine analgesic tolerance was suppressed by nerve injury-induced
      neuropathic pain and formalin- or carrageenan-induced inflammatory pain.
      Tolerance to serum corticosterone elevation by morphine (10 mg/kg), which was
      evaluated by fluorometric assay, was also suppressed by formalin-induced
      inflammatory pain. Moreover, morphine analgesia induced by
      intracerebroventricular (10 nmol) or intrathecal (5 nmol) injection was
      diminished by repeated administration of morphine s.c., and this was also
      suppressed by carrageenan-induced inflammatory pain. These results suggest that
      morphine tolerance is inhibited by several pain stimuli, including neuropathic
      and inflammatory pain, through central mechanisms.

PMID- 22460427
TI  - Comparison of antioxidant activity of compounds isolated from guava leaves and a
      stability study of the most active compound.
AB  - In the present study, quercetin (QT), morin (MR), and quercetin-3-O
      glucopyranoside (QG) isolated from guava leaves were comparatively tested for
      antioxidant activity using DPPH, ABTS, and FRAP methods. QT was the most active
      among them. The free radical scavenging activity of QT was approximately four
      times higher than MR and two times higher than QG. The reducing power of QT was
      eight times higher than MR and two times higher than QG. A mixture of QT with MR
      or QG showed interesting combination effect. The synergistic antioxidant activity
      was obtained when QT was mixed with MR whereas the antagonistic effect was found
      when mixed with QG. The stability study of QT in liquid preparations indicated
      that the decomposition reaction rate of QT could be explained by a kinetic model
      assuming a first-order chemical reaction. The aqueous solution of QT was rapidly
      decomposed with t1/2 of approximately five days whereas QT entrapped in chitosan
      nanoparticles was five times longer. It was concluded that QT was the most active
      antioxidant from guava leaves. Entrapment of QT in chitosan nanoparticles could
      significantly enhance its stability.

PMID- 22460428
TI  - A novel flow-injection analysis system for evaluation of antioxidants by using
      sodium dichloroisocyanurate as a source of hypochlorite anion.
AB  - A flow injection analysis (FIA) system for evaluation of the antioxidant activity
      of a compound capable of scavenging a hypochlorite anion (OCl-), one of the
      reactive oxygen species (ROS), was developed. Aminophenyl fluorescein (APF), a
      fluorescence indicator of ROS, was mixed manually with the test compounds and the
      mixed solution was injected into the FIA system. The injected solution was
      reacted in-line with OCl-, that was produced by using sodium dichloroisocyanurate
      in the presence of 0.1 M CH3CO2Na in H2O. The fluorescence intensity of
      fluorescein generated from non-fluorescent APF was significantly attenuated in
      compounds that had a scavenging effect on OCl-. The precision obtained by the FIA
      system was satisfactory (relative standard deviation < 5.0%) and a rapid assay
      within 0.5 min per sample was achieved. The proposed FIA system was used to
      demonstrate that reduced glutathione, dithiothreitol, and 3-methyl-1-phenyl-5
      pyrazolone (edaravone) showed a significant scavenging effect on OCl-. Therefore,
      the proposed FIA system can be used as a screening assay for OCl--scavenging
      compounds.

PMID- 22460429
TI  - Stability-indicating HPLC method for the determination of the stability of
      oxytocin parenteral solutions prepared in polyolefin bags.
AB  - Oxytocin is very commonly used in clinical settings and is a nonapeptide hormone
      that stimulates the contraction of uterine smooth muscles. In this study the
      stability of extemporaneously compounded oxytocin solutions was investigated in
      polyolefin bags. The sterile preparations of oxytocin were compounded to the
      strength of 0.02 U/mL in accordance with United States Pharmacopeia (USP) <797>
      standards. In order to carry out the stability testing of these parenteral
      products, the solutions were stored under three different temperature conditions
      of -20 degrees C (frozen), 2-6 degrees C (refrigerated), and 22-25 degrees C
      (room temperature). Three solutions from each temperature were withdrawn and were
      assessed for stability on days 0, 7, 15, 21, and 30 as per the USP guidelines.
      The assay of oxytocin was examined by an HPLC method at each time point. No
      precipitation, cloudiness or color change was observed during this study at all
      temperatures. The assay content by HPLC revealed that oxytocin retains greater
      than at least 90% of the initial concentrations for 21 days. There was no
      significant change in pH and absorbance values for 21 days under all the
      conditions of storage. Oxytocin parenteral solutions in the final concentration
      of 0.02 U/mL and diluted in normal saline are stable for at least 30 days under
      frozen and refrigerated conditions for 30 days. At the room temperature, the
      oxytocin solutions were stable for at least 21 days. The stability analysis
      results show that the shelf-life of 21 days observed in this study was far better
      than their recommended expiration dates.

PMID- 22460430
TI  - Synthesis, crystal structures and reactivity of copper(I) amidate complexes with
      aryl halides: insight into copper(I)-catalyzed Goldberg reaction.
AB  - In this paper, copper(I) amidate complexes (2-3), proposed intermediates in
      copper-catalyzed Goldberg reaction, have been prepared and characterized by
      elemental analysis, IR, (1)H NMR and X-ray crystallography. Ancillary ligand
      bis(diphenylphosphino)ferrocene (dppf) has contributed greatly to the stability
      of the copper-amidate complexes due to its strong chelating ability and weak
      intermolecular interactions. Thermal gravimetric analyses are carried out to
      determine the thermal competency of complexes 2-3 as the intermediates of the
      high-temperature Goldberg reactions. Reaction of complexes 2 and 3 with aryl
      halides generates the N-arylation products 5-8, accompanied by the formation of a
      copper(I) complex Cu(dppf)X (X = I or Br) 4, which has been determined by LC-MS
      analysis. These results provide new evidence for the mechanism of copper(I)
      catalyzed Goldberg reaction.

PMID- 22460431
TI  - [A drive for quality: a new forensic unit in Iceland[Editorial]].

PMID- 22460432
TI  - [Screening for prostate cancer[editorial]].

PMID- 22460433
TI  - [Outcome of mitral valve replacement in Iceland].
AB  - INTRODUCTION: Mitral valve replacement (MVR) is the second most common valvular
      replacement procedure after aortic valve replacement (AVR). Studies on the
      outcome of MVR in Iceland have been missing. We therefore studied short and long
      term results following MVR in Iceland, MATERIAL AND METHODS: A retrospective
      nationwide study on 64 patients (mean age 59 years, 63% males) that underwent 66
      MVR procedures in Iceland between 1990-2010. Clinical data was retrieved from
      patient charts and overall survival estimated. The mean follow-up was 7.4 years.
      RESULTS: Mitral regurgitation or stenosis was the indication for MVR in 71% and
      27% of cases, respectively. Nine patients had endocarditis and 8 a recent
      myocardial infarction. The mean logEuroSCORE was 14.9% (range 1.5-88.4), 83% of
      the patients were in NYHA class III/IV preoperatively and 24% had previously
      undergone cardiac surgery. A biological valve was implanted in six cases and a
      mechanical valve used in 60 cases. Concomitant CABG was performed in 41% of
      patients and AVR in 20%. Perioperative myocardial infarction (26%), acute
      respiratory failure (17%), reoperation for bleeding (15%) and acute renal failure
      requiring dialysis (9%) were the most common major complications. Three patients
      required extracorporeal membrane oxygenation (ECMO) and six patients an intra
      aortic balloon pump (IABP) postoperatively. Minor complications were noted in 61%
      of cases. Six patients died within 30 days (9%) and five year survival was 69%.
      CONCLUSION: The frequency of complication following MVR was high and represents
      the severity of the underlying heart disease. The operative mortality in the
      current study was in the lower range compared to other studies.

PMID- 22460434
TI  - [Tetanus: a case report and literature review].
AB  - A 79 year old farmer was referred to the University Hospital with a three days
      history of difficulty in opening his mouth. On examination, both masseters were
      seen to be stiff, suggesting tetanus or jaw-subluxation. An attempt to reduce the
      joint was made, but failed. He subsequently developed progressive respiratory
      difficulties requiring intubation. The farmer had recently cut his finger on
      barbed wire. He had not received tetanus immunization for years and it was not
      clear whether primary immunization had been completed. Tetanus immunoglobulin and
      antibiotics were administered. He proceeded to develop autonomic instability and
      critical illness polyneuropathy requiring 45 days of ICU care. He was finally
      discharged eight months later. The farmer has gradually improved and is now
      living unaided at home. In this article we will review this case and the
      literature on tetanus.

PMID- 22460435
TI  - [Research in pharmacoepidemiology in Iceland].
AB  - Pharmacoepidemiology is a rapidly growing discipline that is useful in studies on
      effects and adverse effects of drugs. During past years and decades databases
      have been built in Iceland that are becoming powerful tools for this kind of
      research. The databases are, however only useful for pharmacoepidemiological
      research if they include personal identification and can be merged. The personal
      identification should be without time limits because in many cases we are
      interested in what happened years or decades ago. The prescriptions database was
      started in 2002 and has dramatically changed the possibilities for
      pharmacoepidemiological studies in Iceland. The main aim of this review is to
      give an overview of the existing databases in Iceland and to encourage research
      in this important field.

PMID- 22460436
TI  - [A 78 year-old man with hyponatremia, malaise and weight loss caused by a
      pituitary mass].
AB  - A 78 year-old male was admitted for rehabilitation after a trans-tibial
      amputation three months earlier. Scheduled training with a prosthetic leg was
      postponed due to muscle atrophy and weakness. As the patient's status
      deteriorated, blood results showed worsening hyponatremia.Work-up revealed
      pituitary insufficiency caused by a pituitary mass. The patient's general health
      improved greatly and the hyponatremia corrected after hormonal replacement
      therapy with hydrocortisone, thyroxin and testosterone was initiated. Key words:
      hyponatremia, malaise, weight loss, pituitary insufficiency, pituitary adenoma.

PMID- 22460438
TI  - Transfer of blastocysts derived from frozen-thawed cleavage stage embryos
      improved ongoing pregnancy.
AB  - PURPOSE: The aim of our study was to compare the transfer of embryos that are
      cryopreserved in cleavage stage after thawing with the transfer of embryos after
      thawing and culture in sequential media until blastocyst formation. METHODS: In
      this prospective clinical study, we have evaluated 134 cycles of ART treatment
      for infertility. Frozen embryos were thawed and then cultured in sequential media
      until blastocyst stage in blastocyst group and were compared with thawed embryos
      in cleavage stage group. RESULTS: Implantation rate was significantly higher in
      blastocyst group (30 %) compared to cleavage group (17 %). No statistical
      differences were reported in chemical and clinical pregnancy rates between
      groups. Ongoing pregnancy rate was significantly higher in blastocyst group
      compared to cleavage group (42.9 vs. 24.6 %). CONCLUSIONS: Our results indicated
      that blastocyst formation after thawing of cleavage stage embryos is a good
      predictor for embryo viability and pregnancy outcome.

PMID- 22460440
TI  - High-order tunneling processes in single-porphyrin transistors.
AB  - Cotunneling and the Kondo effect are observed in single-electron transistors
      incorporating cobalt-porphyrins. These effects are attributed to high-order
      tunneling and strong coupling between the electrodes and the intervening
      porphyrin.

PMID- 22460439
TI  - Multiple reversions of an IL2RG mutation restore T cell function in an X-linked
      severe combined immunodeficiency patient.
AB  - Reversion mosaicism is increasingly being reported in primary immunodeficiency
      diseases, but there have been few cases with clinically improved immune function.
      Here, a case is reported of X-linked severe combined immunodeficiency (SCID-X1)
      with multiple somatic reversions in T cells, which restored sufficient cell
      mediated immunity to overcome viral infection. Lineage-specific analysis revealed
      multiple reversions in T cell receptor (TCR) alphabeta+ and TCRgammadelta+ T
      cells. Diversity of the TCRVbeta repertoire was comparable to normal and,
      furthermore, mitogen-induced proliferation of the patient's T cells was minimally
      impaired compared to healthy controls. In vivo and in vitro varicella antigen
      specific T cell responses were comparable to those of healthy controls, although
      a reduced level of T cell receptor excision circles suggested that recent thymic
      output was low. During long-term evaluation of the patient's immunologic status,
      both the number of CD4+ and CD8+ T cells and T cell proliferation responses were
      stable and the patient remained healthy. This case demonstrates that multiple but
      restricted somatic reversions in T cell progenitors can improve the clinical
      phenotype of SCID-X1.

PMID- 22460441
TI  - Diagnostic modalities for distant metastasis in head and neck squamous cell
      carcinoma: are we changing life expectancy?
AB  - OBJECTIVES/HYPOTHESIS: To determine if the various imaging modalities for distant
      metastasis (DM) diagnosis alters life expectancy in head and neck squamous cell
      carcinoma (HNSCC). STUDY DESIGN: Retrospective. METHODS: One hundred seventy
      patients (mean age, 59.1 years; male:female, 135:35) with HNSCC who developed DM
      were reviewed. The main outcome measures were the method of DM diagnosis and time
      from DM diagnosis to death while controlling for clinical parameters (age,
      gender, tobacco status, primary tumor site, initial TNM classification, number
      and site of DM, administration of palliative chemotherapy). RESULTS: Tumor
      subsites were: 40 oral cavity, 75 oropharynx, 36 larynx, 10 hypopharynx, one
      nasopharynx, and eight unknown primary. Of the patients, 16.5% (28/170) had
      distant metastasis at presentation; the remaining 142 patients were diagnosed
      with DM at a median of 324 days from diagnosis. Although patients diagnosed with
      DM by positron-emission tomography (PET) scan were more likely to have multiple
      DM sites (P = .0001), there were no differences in life expectancy in patients
      who were diagnosed with or without PET scan (median, 185 vs. 165 days, P = .833).
      There were no differences in life expectancy based on age, gender, site of
      primary tumor, or number/site of DM. The use of palliative chemotherapy resulted
      in a significantly longer life expectancy (median, 285 vs. 70 days; P = .001).
      CONCLUSIONS: Although a PET scan is more likely to diagnose multiple DM sites,
      there was no difference in life expectancy based on imaging modality. Patients
      who are symptomatic from their distant metastasis have a worse life expectancy,
      and palliative chemotherapy was able to increase life expectancy, even in
      patients who were symptomatic from the distant metastasis.

PMID- 22460442
TI  - A study of surnames in China through isonymy.
AB  - The isonymy structure of 1.28 billion people registered in China's National
      Citizen Identity Information System was studied at the provincial, prefectural,
      and county administrative division levels. The isonymy was 0.026 for China as a
      whole. The average value of isonymy was 0.033 for the 30 provinces, 0.035 for the
      334 prefectures, and 0.040 for the 2811 counties. The isonymy in China was much
      higher than in other countries. This finding may be partly explained by the low
      number of surnames in the Chinese language. Two regional features can be
      identified from the geographic distributions of isonymy. One feature is that the
      middle and lower reaches of the Yangtze River had the lowest values of isonymy at
      both the provincial and county levels. The second feature is that most counties
      with the highest values of isonymy were distributed in the provinces with high
      proportions of ethnic minorities. According to the dendrogram of surname
      distances, several clusters could be identified. Most provinces in a cluster were
      conterminous with one another. The one exception could be explained by demic
      migration called "braving the journey to the northeast of China." Isolation by
      distance could be detected because the correlation coefficients between Nei's
      distance and the geographic distances at the provincial, prefectural, and county
      levels were 0.64, 0.43, and 0.37, respectively. Human behaviors in Chinese
      history that may have caused these results have been discussed, including
      cultural origin, migration, residential patterns, and ethnic distribution.

PMID- 22460443
TI  - Individualized medicine, health medicine, and constitutional theory in Chinese
      medicine.
AB  - The patterns of modern science and changes in the medical model can result in the
      transformation of the current state of individualized and health medicines into
      being the primary trend in medical development. Chinese and Western medical
      systems are dissimilar in terms of value orientations, thinking style, and
      research directions because of their different historical and cultural
      backgrounds. Individualized treatment in modern medicine is mainly established
      based on individual genome information and the differences in mononucleotide
      polymorphisms. However, such treatment method is expensive, creates an uncertain
      genetic marker, and leads to different result interpretations, among other
      problems. The Chinese constitutional theory developed in the 1970s expresses the
      principle behind Chinese health medicine and individual treatment and provides
      the corresponding methods. The Chinese constitutional theory divides the
      constitution of the Chinese population into nine categories based on established
      classification criteria. It promotes the study of the relationship of each
      constitution to diseases and Chinese medicine preparation toward adjusting the
      constitution and preventing diseases. The theory also provides methods and tools
      for individualized treatment. Constitution identification shows the direction and
      provides the core technology for the evaluation of the health status. By
      combining the developments in modern biotechnology, new diagnostic techniques and
      treatment models of constitution-differentiation, disease-differentiation, and
      syndrome-differentiation can be established for the development of individualized
      Chinese medicine treatment and health medicine for the international medical
      community.

PMID- 22460437
TI  - Mesocosms of aquatic bacterial communities from the Cuatro Cienegas Basin
      (Mexico): a tool to test bacterial community response to environmental stress.
AB  - Microbial communities are responsible for important ecosystem processes, and
      their activities are regulated by environmental factors such as temperature and
      solar ultraviolet radiation. Here we investigate changes in aquatic microbial
      community structure, diversity, and evenness in response to changes in
      temperature and UV radiation. For this purpose, 15 mesocosms were seeded with
      both microbial mat communities and plankton from natural pools within the Cuatro
      Cienegas Basin (Mexico). Clone libraries (16S rRNA) were obtained from water
      samples at the beginning and at the end of the experiment (40 days). Phylogenetic
      analysis indicated substantial changes in aquatic community composition and
      structure in response to temperature and UV radiation. Extreme treatments with
      elevation in temperature or UV radiation reduced diversity in relation to the
      Control treatments, causing a reduction in richness and increase in dominance,
      with a proliferation of a few resistant operational taxonomic units. Each phylum
      was affected differentially by the new conditions, which translates in a
      differential modification of ecosystem functioning. This suggests that the impact
      of environmental stress, at least at short term, will reshape the aquatic
      bacterial communities of this unique ecosystem. This work also demonstrates the
      possibility of designing manageable synthetic microbial community ecosystems
      where controlled environmental variables can be manipulated. Therefore, microbial
      model systems offer a complementary approach to field and laboratory studies of
      global research problems associated with the environment.

PMID- 22460444
TI  - Medical applications of phytoestrogens from the Thai herb Pueraria mirifica.
AB  - Pueraria mirifica Airy Shaw et Suvatabandhu is a medicinal plant endemic to
      Thailand. It has been used in Thai folklore medicine for its rejuvenating
      qualities in aged women and men for nearly one hundred years. Indeed, it has been
      claimed that P. mirifica contains active phytoestrogens (plant substances with
      estrogen-like activity). Using high performance liquid chromatography, at least
      17 phytoestrogens, mainly isoflavones, have been isolated. Thus, fairly
      considerable scientific researches, both in vitro in cell lines and in vivo in
      various species of animals including humans, have been conducted to date to
      address its estrogenic activity on the reproductive organs, bones, cardiovascular
      diseases and other climacteric related symptoms. The antioxidative capacity and
      antiproliferative effect on tumor cell lines have also been assessed. In general,
      P. mirifica could be applicable for preventing, or as a therapeutic for, the
      symptoms related to estrogen deficiency in menopausal women as well as in
      andropausal men. However, the optimal doses for each desirable effect and the
      balance to avoid undesired side effects need to be calculated before use.

PMID- 22460445
TI  - Stroke prevention: an update.
AB  - Stroke is a personal, familial, and social disaster. It is the third cause of
      death worldwide, the first cause of acquired disability, the second cause of
      dementia, and its cost is astronomic. The burden of stroke is likely to increase
      given the aging of the population and the growing incidence of many vascular risk
      factors. Prevention of stroke includes--as for all other diseases--a "mass
      approach" aiming at decreasing the risk at the society level and an individual
      approach, aiming at reducing the risk in a given subject. The mass approach is
      primarily based on the identification and treatment of vascular risk factors and,
      if possible, in the implementation of protective factors. These measures are the
      basis of primary prevention but most of them have now been shown to be also
      effective in secondary prevention. The individual approach combines a vascular
      risk factor modification and various treatments addressing the specific subtypes
      of stroke, such as antiplatelet drugs for the prevention of cerebral infarction
      in large and small artery diseases of the brain, carotid endarterectomy or
      stenting for tight carotid artery stenosis, and oral anticoagulants for the
      prevention of cardiac emboli. There is a growing awareness of the huge evidence
      to-practice gap that exists in stroke prevention largely due to socio-economic
      factors. Recent approaches include low cost intervention packages to reduce blood
      pressure and cheap "polypills" combining in a single tablet aspirin and several
      drugs to lower blood pressure and cholesterol. Polypill intake should however not
      lead to abandon the healthy life-style measures which remain the mainstay of
      stroke prevention.

PMID- 22460447
TI  - Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and
      potential for cutaneous regeneration.
AB  - Umbilical cord mesenchymal stem cells (MSCs) are a unique, accessible, and non
      controversial source of early stem cells that can be readily manipulated. As the
      most common pluripotent cell, bone marrow-derived MSCs display limitations with
      the progress of stem cell therapy. By contrast, umbilical cord-derived cells,
      which have plentiful resources, are more accessible. However, several uncertain
      aspects, such as the effect of donor selection or culture conditions, long-term
      therapeutic effects, product consistency, and potential tumorigenicity, are the
      bottleneck in this clinical therapy. MSCs are predicted to undergo an
      unprecedented development in clinical treatment when a generally acknowledged
      criterion emerges. In the current paper, we highlight the application of
      umbilical cord-derived MSCs in skin therapies based on our previous studies, as
      well as the achievements of our peers in this field. This paper focuses on the
      strategies, challenges, and potential of this novel therapy.

PMID- 22460446
TI  - Nicotinic acetylcholine receptor alpha7 subunit: a novel therapeutic target for
      cardiovascular diseases.
AB  - Inflammation is important in the pathogenesis and development of cardiovascular
      diseases. Recent studies show that vagus nerve stimulation inhibits pro
      inflammatory cytokine production through "the cholinergic anti-inflammatory
      pathway," more specifically via the alpha7 nicotinic acetylcholine receptor
      (alpha7nAChR). In the current study, the role of the cholinergic anti
      inflammatory pathway during septic shock, hypertension, and myocardial infarction
      is reviewed, and its possible clinical implications in cardiovascular diseases
      are discussed.

PMID- 22460448
TI  - Exploring the cancer genome in the era of next-generation sequencing.
AB  - The emergence of next-generation sequencing technologies has led to dramatic
      advances in cancer genome studies. The increased efficiency and resolution of
      next-generation sequencing greatly facilitate the detection of genetic, genomic,
      and epigenomic alterations, such as single nucleotide mutations, small insertions
      and deletions, chromosomal rearrangements, copy number variations, and DNA
      methylation. Comprehensive analysis of cancer genomes through approaches of whole
      genome, exome, and transcriptome sequencing has significantly improved the
      understanding of cancer biology, diagnosis, and therapy. The present study
      briefly reviews the recent pioneering studies on cancer genome sequencing and
      provides an unprecedented insight into the landscape of genomic alterations in
      human sporadic cancers.

PMID- 22460451
TI  - Integration of current identity-based district-varied health insurance schemes in
      China: implications and challenges.
AB  - With China's great efforts to improve public health insurance, clear progress has
      been achieved toward the ambitious full health insurance coverage strategy for
      all. The current health insurance schemes in China fall into three categories:
      urban employee basic health insurance scheme, urban resident scheme, and new
      rural cooperative medical system. Despite their phasic success, these
      substantially identity-based, district-varied health insurance schemes have
      separate operation mechanisms, various administrative institutions, and
      consequently poor connections. On the other hand, the establishment and
      implementation of various health insurance schemes provide the preconditioning of
      more sophisticated social health insurance schemes, the increase in the income of
      urban and rural people, and the great importance attached by the government.
      Moreover, the reform of the "Hukou" (household register) system provides
      economical, official, and institutional bases. Therefore, the establishment of an
      urban-rural integrated, citizen-based, and nationwide-universal health insurance
      scheme by the government is critically important to attain equality and national
      connection. Accordingly, the differences between urban and rural areas should be
      minimized. In addition, the current schemes, administrative institutions, and
      networks should be integrated and interconnected. Moreover, more expenditure on
      health insurance might be essential for the integration despite the settings of
      global financial crisis. Regardless of the possible challenges in implementation,
      the proposed new scheme is promising and may be applied in the near future for
      the benefit of the Chinese people and global health.

PMID- 22460449
TI  - Natural killer cell lines in tumor immunotherapy.
AB  - Natural killer (NK) cells are considered to be critical players in anticancer
      immunity. However, cancers are able to develop mechanisms to escape NK cell
      attack or to induce defective NK cells. Current NK cell-based cancer
      immunotherapy is aimed at overcoming NK cell paralysis through several potential
      approaches, including activating autologous NK cells, expanding allogeneic NK
      cells, usage of stable allogeneic NK cell lines and genetically modifying fresh
      NK cells or NK cell lines. The stable allogeneic NK cell line approach is more
      practical for quality-control and large-scale production. Additionally,
      genetically modifying NK cell lines by increasing their expression of cytokines
      and engineering chimeric tumor antigen receptors could improve their specificity
      and cytotoxicity. In this review, NK cells in tumor immunotherapy are discussed,
      and a list of therapeutic NK cell lines currently undergoing preclinical and
      clinical trials of several kinds of tumors are reviewed.

PMID- 22460452
TI  - Evaluation of the harmonic scalpel in open surgery for abdominal aortic aneurysm.
AB  - The harmonic scalpel is a hemostatic device primarily designed for use in
      laparoscopic surgery. During the last few years, many surgeons have begun to use
      the harmonic scalpel in open surgery. Several papers have cited the benefits of
      the device compared with conventional knot-tying techniques; however, no evidence
      showing the advantages of using the harmonic scalpel in complicated abdominal
      aortic aneurysm (AAA) surgery has been presented. The aim of the present study is
      to determine the value of the harmonic scalpel in open operation for AAA. A total
      of 153 patients who underwent open surgery for AAA at the Department of Vascular
      Surgery of Guangdong General Hospital, China between January 2001 and December
      2010, were retrospectively analyzed. Open surgery performed with the harmonic
      scalpel on 105 patients was compared with open operation using conventional knot
      tying techniques on 48 patients. The operative time, intraoperative blood loss,
      total postoperative drainage fluid volumes, hospital stay, and postoperative
      complications between the two groups were compared. The harmonic scalpel group
      was associated with a shorter operation time (113.2 +/- 23.6 min vs. 232.1 +/-
      39.2 min, P < 0.01) and lower intraoperative blood loss (126.1 +/- 96.6 ml vs.
      592.1 +/- 207.2 ml, P < 0.01). Postoperative drainage fluid volumes were greater
      in the conventional surgery group than in the harmonic scalpel group (702.1 +/-
      192.8 ml vs. 198.5 +/- 97.4 ml, P < 0.01). The hospital stay was shorter for the
      harmonic scalpel group than for the conventional surgery group (10.7 +/- 3.3 d
      vs. 16.5 +/- 4.7 d, P < 0.05). No differences between the postoperative
      complications or hospital mortality of the two groups were found. The harmonic
      scalpel is a safe and minimally invasive tool in open surgery for AAA and is
      associated with shorter operative time, shorter hospital stay, and lower
      intraoperative blood loss and postoperative drainage fluid volumes compared with
      conventional knot-tying techniques.

PMID- 22460453
TI  - Clinical decision-making by the emergency department resident physicians for
      critically ill patients.
AB  - The application of main methodologies for clinical decision-making by residents
      in emergency medical practice was assessed, and issues in this area were
      investigated. The treatments provided to 2 611 critical patients by the Emergency
      Department of Peking Union Medical College Hospital were analyzed by independent
      investigators who evaluated the main clinical decision-making processes applied
      by the hospital residents. The application of decision-making strategies by PG1
      and PG3 groups, which means the residents in first year and the third year, were
      compared. The patients were treated according to pattern recognition (43.0%),
      hypothetico-deductive reasoning (23.4%), event-driven models (19.3%), and rule
      using algorithms (5.9%). A significant difference was found between PG1 and PG3
      groups (chi(2)= 498.01, P < 0.001). Pattern recognition and hypothetic-deductive
      methods were the most common techniques applied by emergency physicians in
      evaluating critically ill patients. The decision-making processes applied by
      junior and senior residents were significantly different, although neither group
      adequately applied rule-using algorithms. Inclusion of clinical decision-making
      in medical curricula is needed to improve decision-making in critical care.

PMID- 22460450
TI  - Progress in tumor vascular normalization for anticancer therapy: challenges and
      perspectives.
AB  - Antitumor angiogenic therapy has been shown promising in the treatment of several
      advanced cancers since the approval of the first antiangiogenic drug Avastin in
      2004. Although the current antiangiogenic drugs reduce the density of tumor blood
      vessels and result in tumor shrinkage at the early stage of treatment, recent
      studies have shown that antiangiogenic therapy has transient and insufficient
      efficacy, resulting in tumor recurrence in patients after several months of
      treatment. Blockage of blood and oxygen supplies creates a hypoxic and acidic
      microenvironment in the tumor tissues, which fosters tumor cells to become more
      aggressive and metastatic. In 2001, Jain proposed tumor vascular normalization as
      an alternative approach to treating cancers based on the pioneering work on tumor
      blood vessels by several other researchers. At present, normalizing the
      disorganized tumor vasculature, rather than disrupting or blocking them, has
      emerged as a new option for anticancer therapy. Preclinical and clinical data
      have shown that tumor vascular normalization using monoclonal antibodies,
      proteins, peptides, small molecules, and pericytes resulted in decreased tumor
      size and reduced metastasis. However, current tumor vascular normalizing drugs
      display moderate anticancer efficacy. Accumulated data have shown that a variety
      of vasculogenic/angiogenic tumor cells and genes play important roles in tumor
      neovascularization, growth, and metastasis. Therefore, multiple-targeting of
      vasculogenic tumor cells and genes may improve the efficacy of tumor vascular
      normalization. To this end, the combination of antiangiogenic drugs with tumor
      vascular normalizing therapeutics, as well as the integration of Western medicine
      with traditional Chinese medicine, may provide a good opportunity for discovering
      novel tumor vascular normalizing drugs for an effective anticancer therapy.

PMID- 22460454
TI  - Scientific publications on systematic review and meta-analysis from Chinese
      authors: a 10-year survey of the English literature.
AB  - Systematic reviews and meta-analyses are playing an increasingly important role
      in clinical research and practice. This study aimed to measure the scientific
      production of systematic review and meta-analysis from the three major regions of
      China: the Mainland (ML), Hong Kong (HK), and Taiwan (TW). English articles on
      systematic review and meta-analysis from ML, HK, and TW from 2001 to 2010 were
      retrieved from the PubMed database. The total number of articles, impact factors
      (IF), and articles published in high-impact journals were conducted for quantity
      and quality comparisons among the three regions. There were 1 587 published
      articles from ML (1 292), HK (203), and TW (92) during the past ten years. The
      annual total numbers of articles in the three regions increased significantly
      from 2001 to 2010 (from 13 to 677). The number of articles from ML has exceeded
      that from TW since 2001, and surpassed that from HK in 2003. The accumulated IF
      of articles from ML (3 488.24) was higher than those from HK (493.16) and TW
      (216.39). HK had the highest average IF of 3.31, followed by ML of 2.90 and TW of
      2.85. Researchers from HK published a larger proportion of papers in high-impact
      journals than those from ML and TW. The Cochrane Database of Systematic Reviews
      was the most popular journal in China. Chinese authors have been very active to
      enhance the systematic review and meta-analysis research over the past ten years,
      especially in ML. The gap between ML and the other two regions has been narrowed.
      But there is still considerable room for Chinese authors to improve their studies
      on systematic review and meta-analysis.

PMID- 22460455
TI  - Local retrograde and destination transfer of physiological regulators as an
      important regulatory system and its role. Facts and hypothesis.
AB  - In recent decades, among many physiological regulatory systems operating as local
      and central controls, the mechanism of the local regulatory system based on the
      uptake and retrograde transfer of hormones and other physiological regulators to
      the places of their secretion or their destination transfer to nearby structures
      has become precisely understood. The system of the retrograde transfer and local
      destination transfer of the physiological regulators, situated between endocrine
      and paracrine regulation, operates primarily on the basis of specific
      morphological adaptations of the local blood circulatory system and lymphatic
      system. These adaptations enable the transfer of the regulatory molecules through
      the walls of blood and lymph vessels and locally increase their concentrations in
      the arterial blood supplying the organ secreting them (retrograde transfer) or a
      nearby organ (destination transfer). Extensive studies on the structure and
      functions of the retrograde and destination transfer system have focused on
      several key areas: the female and male reproductive organs, the perihypophyseal
      vascular complex (the venous cavernous sinus and the internal carotid artery or
      the rete mirabile of the internal carotid artery or maxillary artery), and the
      periophthalmic vascular complex (the venous ophthalmic sinus or plexus and the
      rete mirabile of the external ophthalmic artery). The local retrograde transfer
      of regulatory molecules not only allows them to be reused but also influences
      their production by a feedback mechanism. The local destination transfer of
      physiological regulators can selectively supply nearby organs with certain
      regulatory factors and thereby affect their function. Many observations indicate
      that the retrograde and local destination transfer of hormones and other
      biologically active substances may be a universal physiological regulatory
      mechanism, operating with only minor modifications in various species of animals
      and in humans. This review evaluates the most important published experimental
      studies and presents facts and hypothesis on the regulatory role of the
      retrograde and destination transfer of many steroid hormones, prostaglandins,
      pheromones, neurotransmitters (neurohormones) and CO in male and female
      reproductive physiology, in the physiology of the central nervous system and
      hypophysis and in eye function.

PMID- 22460456
TI  - Cardiac effects of osteostatin in mice.
AB  - Mouse parathyroid hormone-related peptide (PTHrP) is a peptide hormone consisting
      of 139 amino acids. It is target of proteolysis resulting in circulation of N-
      and C-terminal peptides. C-terminal PTHrP peptides act in a PTH/PTHrP receptor
      independent way with a minimal peptide sequence required to exert these effects
      covering amino acids 107-111 also known as osteostatin. Although effects of
      osteostatin on cardiac hypertrophy have been described in vitro, the in vivo
      relevance of these findings remained to be defined. The study was performed in
      two experimental series. In the first series, mice were randomly distributed into
      placebo or treatment group (each n=7) and osteostatin was administered via
      osmotic minipumps. In the second series, mice underwent a banding of the thoracic
      aorta to induce pressure overload and were again randomly distributed into
      placebo or treatment group (n=9 each). After 14 days, mice were anaesthetized and
      cardiac function, ECG, and cardiac hypertrophy were determined. Osteostatin
      increased the expression of ANF and reduced P-wave duration with little effects
      on cardiac performance in mice without pressure overload. In TAC banded mice,
      however, osteostatin significantly reduced TAC-induced loss of body weight,
      induced right ventricular hypertrophy, and reduced P-wave duration again. In
      osteostatin treated mice with pressure overload, the protein kinase C-dependent
      phosphorylation of connexin 43 was preserved. In summary, osteostatin attenuated
      pressure-overload-dependent loss of body weight without affecting left
      ventricular hypertrophy or left ventricular function but preserved atrial
      conduction. Osteostatin exerts moderate cardioprotective effects in mice under
      hemodynamic stress.

PMID- 22460457
TI  - Effects of chronic neuronal nitric oxide-synthase inhibition on arterial function
      and structure in spontaneously hypertensive rats.
AB  - While the effect of chronic non-specific NO-synthase inhibition in the
      cardiovascular system has been recognized under normotensive and hypertensive
      conditions, there are no data relating the long-term inhibition of neuronal NO
      synthase (nNOS) in essential hypertension. The aim of this study was to
      investigate the long-term effect of nNOS inhibitor 7-nitroindazole (7-NI)
      administration on arterial function and structure in spontaneously hypertensive
      rats (SHR). Ten weeks old SHR were divided in two groups: control group and group
      administered 7-NI (10 mg/kg/day) for six weeks in drinking water. Systolic blood
      pressure (SBP) was measured using the plethysmographic method. The vasoactivity
      of isolated thoracic aorta (TA) and mesenteric artery (MA) was recorded via
      changes in isometric tension, and the geometry of both arteries was measured
      using light microscopy. Chronic treatment with 7-NI did not affect either SBP or
      heart/body weight ratio. Acetylcholine-induced relaxation of both arteries was
      unchanged after 7-NI. 7-NI administration did not affect the sensitivity and
      contraction to exogenous noradrenaline in TA, whereas both parameters were
      augmented in MA. The contractile response of MA induced by transmural nerve
      stimulation (endogenous noradrenaline) was unaffected after 7-NI. The mass of TA
      wall was unchanged, whereas hypertrophy was observed in MA after 7-NI. In
      summary, although SBP and endothelial function were not changed after chronic
      nNOS inhibition, the contractile and structural properties of TA and MA were
      affected differently. The data suggest that nNOS triggers original and tissue
      specific regulatory pathways in essential hypertension.

PMID- 22460458
TI  - In vitro study on the effects of some selected agonists and antagonists of
      alpha(1)-adrenergic receptors on the contractility of the aneurysmally-changed
      aortic smooth muscle in humans.
AB  - The study included 18 sections of the aneurysmally-changed abdominal aortas,
      obtained from patients of the Provincial Specialist Hospital in Wroclaw and 18
      sections of normal abdominal aortas obtained from swine. The collected samples
      were placed horizontally in the incubation chamber. Changes in their transverse
      section area were registered. They were stretched to a tension of 5 mN. Krebs
      Henseleit buffer was used as the incubatory environment. Incubation of the
      sections was performed at a temperature of 37 degrees C, in the gaseous mixture
      of oxygen and carbon dioxide used in the following proportion: 95% of O(2) and 5%
      of CO(2). Contractions of the aorta were registered with isotonic transducers
      (Letica Scientific Instruments). In the studies, we examined the influence of
      alpha(1)-adrenergic receptors (and their subtypes alpha(1A), alpha(1B),
      alpha(1D)) on the contractility of the aortic muscle in humans and swine by their
      stimulation or inhibition with some selected agonists or antagonists. This time,
      it was shown that the stimulation of alpha(1)-adrenergic receptors leads to
      contractions of the human and swine aortic muscle; the observed increase in the
      muscle tone may follow from the stimulation of all subtypes of alpha-1 receptor
      (alpha(1A), alpha(1B), alpha(1D)). All three subtypes of 1-adrenergic receptor
      are engaged in vasoconstriction, especially of alpha(1A) and alpha(1D) subtypes;
      the alpha(1B) subtype is less significant for aortic contractility. The
      contractile response of the aneurysmally-changed abdominal aorta in humans to
      agonists of alpha-adrenergic receptors was significantly less intense than that
      of the normal porcine aorta. It can be concluded that aneurysms influence the
      contractile response of the aorta.

PMID- 22460459
TI  - The effects of long-term melatonin treatment on plasma liver enzymes levels and
      plasma concentrations of lipids and melatonin in patients with nonalcoholic
      steatohepatitis: a pilot study.
AB  - The present study represents the follow-up of our initial observations designed
      to investigate whether in patients with nonalcoholic steatohepatitis (NASH) the
      beneficial effect of 12-week course of melatonin (MT) on liver enzymes could be
      maintained with prolonged period of treatment and to analyze whether biochemical
      treatment responses could be sustainable after melatonin discontinuation. Forty
      two patients with histologically proven NASH (30 treated with melatonin 2x5 mg
      daily, 12 controls receiving placebo) enrolled to our previous 3-month study
      agreed to take part of subsequent 12 weeks treatment followed by 12-week follow
      up period. Enrolled patients had biochemical determinations every six weeks
      during the melatonin treatment period and again after 12 weeks of follow-up.
      Significant reduction in median alanine aminotransferase (ALT) levels between
      baseline and week 18, week 24 and follow-up was observed in both MT-treated and
      control group: 43% and 31%, 42% and 33%, 32% and 31%. Aspartate aminotransferase
      (AST) and gamma-glutamyl transpeptidase (GGT) levels decrease significantly only
      in MT-treated group. In MT-treated group mean percentage change in AST level
      below baseline at week 18, at week 24 and at follow-up was 45%, 33% (p<0.05) and
      8% (ns), respectively. The evolution of GGT levels was as follows: the mean
      percentage reduction in GGT below baseline level at week 18, 24 and follow-up
      was: 48%, 52% and 38% (p<0.05), respectively. In both MT-treated and control
      group plasma cholesterol, triglicerydes and glucose concentrations as well as
      plasma alkaline phosphatase persisted within normal values during the prolonged
      study period. Plasma concentration of melatonin (pg/ml) in MT-treated group
      averaged 7.5+/-3.5 at baseline and increased to 52.5+/-17.5 at 24th week. The
      results of our study demonstrating beneficial effect of melatonin on liver
      enzymes in patients with NASH would seem to encourage further controlled trials
      of melatonin given over a longer period of time with liver histology as end
      point.

PMID- 22460460
TI  - A new model of gastric bleeding induced in rats by aspirin plus clopidogrel under
      stimulation of acid secretion. Prophylactic effects of antiulcer drugs.
AB  - We set up a new model of gastric bleeding induced by the luminal perfusion of
      aspirin (ASA) in rats pretreated with clopidogrel under conditions where acid
      secretion is stimulated, and examined the effect of antiulcer drugs on the
      bleeding. Under urethane anesthesia, acid secretion was stimulated by i.v.
      infusion of histamine (8 mg/kg/h), and two catheters were inserted into the
      stomach, one from the esophagus and another from the duodenum. The stomach was
      perfused with 25 mM ASA at a rate of 0.1 ml/min using an infusion pump, and
      gastric bleeding was measured as hemoglobin concentration in the perfusate
      collected every 15 min. Clopidogrel (30 mg/kg) was given orally 24 h before the
      perfusion. Various antiulcer drugs were given intraduodenally 30 min before the
      ASA treatment. Perfusion of the stomach with ASA provoked little gastric bleeding
      or damage even when acid secretion was stimulated. Pretreatment with clopidogrel
      significantly increased the bleeding and damage caused by ASA. The bleeding and
      lesions produced by ASA plus clopidogrel were significantly prevented by
      pretreatment with famotidine and omeprazole. Mucosal protective drugs such as
      rebamipide, irsogladine and teprenone also prevented gastric bleeding response to
      ASA/clopidogrel under conditions of acid secretion, although the effect was less
      pronounced than that of the antisecretory drugs. We conclude that clopidogrel
      increases gastric bleeding induced by ASA when acid secretion is stimulated. Both
      antisecretory and mucosal protective drugs are effective in reducing gastric
      bleeding under such conditions. This model is useful for the screening of drugs
      that protect against gastric bleeding.

PMID- 22460461
TI  - The effect of exogenous apelin on the secretion of pancreatic juice in
      anaesthetized rats.
AB  - Apelin is known to stimulate cholecystokinin (CCK) and inhibit insulin release,
      however the mechanisms on pancreatic secretion remain unclear. The present study
      aimed to determine the expression of apelin and apelin receptor in the pancreas
      by immunofluorescence studies and the effect of exogenous apelin on the secretion
      of pancreatic juice in anesthetized rats. Pancreatic-biliary juice (P-BJ) was
      collected from Wistar rats treated with apelin (10, 20 and 50 nmol/kg b.w.,
      boluses given every 30 min intravenously or intraduodenaly). The same apelin
      doses were administered to rats subjected to intraduodenal tarazapide, capsaicin
      or vagotomy. Pancreatic blood flow was measured by a laser doppler flowmeter.
      Direct effects of apelin were tested on dispersed acinar cells. Apelin receptor
      was expressed on acinar cells, pancreatic duct and islets cells, whereas apelin
      in pancreatic acini, but not in the islets. Intravenous apelin decreased P-BJ
      volume, protein and trypsin outputs in a dose-dependent manner. In contrast,
      intraduodenal apelin stimulated P-BJ secretion. Pharmacological block of mucosal
      CCK(1) receptor by tarazepide, vagotomy and capsaicin pretreatment abolished the
      effects of intravenous and intraduodenal apelin on P-BJ volume, protein and
      tryspin outputs. Apelin decreased the pancreatic blood flow. Apelin at 10(-6) M
      increased the release of amylase from non-stimulated and CCK-8-stimulated acinar
      cells. In conclusion, apelin can affect the exocrine pancreas through a complex
      mechanism involving local blood flow regulation and is driven by vagal nerves.

PMID- 22460462
TI  - Hydrogen sulfide-induced colonic mucosal cytoprotection involves T-type calcium
      channel-dependent neuronal excitation in rats.
AB  - Hydrogen sulfide (H(2)S) is generated from L-cysteine by certain enzymes
      including cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS),
      and causes excitation of nociceptors mainly via activation of Ca(v)3.2 T-type
      Ca(2+) channels in the peripheral tissue, facilitating somatic and colonic pain.
      Here, we investigated whether sensory nerves and Ca(v)3.2 are involved in the
      H(2)S-induced mucosal cytoprotection against 2,4,6-trinitrobenzenesulfonic acid
      (TNBS)-induced colitis in rats. Colitis was evaluated 3 days after intracolonic
      (i.c.) TNBS in the rat. Phosphorylation of ERK in the spinal dorsal horn was
      detected by immunohistochemistry. Protein expression of Ca(v)3.2 in the dorsal
      root ganglia (DRG) and of CSE and CBS in the colon was determined by Western
      blotting. Repeated i.c. NaHS significantly suppressed the TNBS-induced colitis in
      rats, an effect prevented by ablation of sensory nerves with repeated
      administration of capsaicin. Repeated pretreatment with T-type Ca(2+) channel
      blockers including ethosuximide significantly reduced the protective effects of
      repeated i.c. NaHS in the rats with TNBS-induced colitis. A single i.c.
      administration of NaHS induced ethosuximide-sensitive prompt phosphorylation of
      ERK in the spinal dorsal horn at T13 and L6-S1 levesl in the rats 1 day or 3 days
      after TNBS treatment, but not in naive rats. Ca(v)3.2 protein was upregulated in
      DRG 1 day after i.c. TNBS in rats, while CSE, but not CBS, protein was
      downregulated in the colon. Our findings suggest that luminal H(2)S causes
      excitation of sensory nerves most probably by activating Ca(v)3.2 T-type Ca(2+)
      channels that are upregulated in the early stage of colitis, leading to colonic
      mucosal cytoprotection in rats.

PMID- 22460463
TI  - Gonadoliberin (GnRH) and its copper complex (Cu-GnRH) enzymatic degradation in
      hypothalamic and pituitary tissue in vitro.
AB  - The amount of decapeptide decapeptide gonadoliberin (GnRH) that reaches pituitary
      gland depends not only on transcriptional, translational and posttranslatonal
      processes but also on the extent of degradation exerted by specific proteolytic
      enzymes. The copper-gonadoliberin (Cu-GnRH) complex preserves the native GnRH
      amino acid sequence but contains Cu(2+) ion bound to the nitrogen atom at the
      imidazole ring of the His(2). The aim of this study was to determine whether GnRH
      and Cu-GnRH molecules differ in their susceptibility to proteolysis in male rat
      hypothalamic and pituitary tissue in vitro. RIA was applied for a time-dependent
      study based on 0-90 min incubations at 30 degrees C of exogenous peptide (2.5 MUg
      GnRH or Cu-GnRH) in respective hypothalamic/pituitary supernatant and pellet
      fractions. To compare the protective effect of bacitracin, a competitive PEP
      inhibitor, incubations were made with (125 MUg/sample) or without an inhibitor.
      In the second experiment 100 MUg of GnRH or Cu-GnRH were incubated for 5 h at 37
      degrees C in hypothalamic and pituitary tissue in vitro and then HPLC analysis
      was applied both to characterize the elution pattern of GnRH and Cu-GnRH
      degradation products as well as to determine their AA composition. In both
      tissues, Cu-GnRH remained more resistant to enzymatic degradation and fully
      protected in the presence of bacitracin. In conclusion, the obtained data suggest
      that copper ion changed GnRH conformation and significantly modified its
      physiological properties due to a hindered endopeptidases access to specific AA
      bonds. Therefore, the Cu-GnRH complex might be considered as GnRH analog
      potentially able to prolong the occupation of a GnRH receptor at the gonadotrope
      cells.

PMID- 22460464
TI  - Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in
      apoE-knockout mice.
AB  - Our interest focused on an open question whether AT-(1-7), nonpeptide receptor
      agonist: AVE 0991, is able to ameliorate atherosclerosis. We used an
      apolipoprotein E (apoE) - knockout mice model of atherosclerosis. Experimental
      groups received the same diet as control, mixed with: AVE 0991 at a dose of 0.58
      MUmol/kg b.w./day, perindopril at a dose of 0.4 mg/kg b.w./day or with tiorphan
      at a dose of 2.5 mg/kg b.w./day. A-779 [(D-alanine)-angiotensin (1-7)] was given
      at a dose of 3.3 mg/kg b.w., 3 times a week i.p. Measured by "en face" method,
      the percentage of occupied by Sudan IV-stained surfaces were as follows: 14.2+/
      1.9 % in control group, whereas in AVE 0991-treated as well as in perindopril
      treated groups percentages were statistically significantly lower. In tiorphan
      group there was no change comparing to control group, whereas in A-779 group
      percentage was statistically significantly higher. "Cross-section" of aortic
      roots revealed also the difference in atherosclerotic lesions. The mean surfaces,
      occupied by oil red O-stained changes were: 91.213+/-8.123 MUm(2) in control
      group, while in AVE 0991-treated as well as in perindopril-treated groups lesions
      were statistically significantly lower. In tiorphan group there was no change;
      however, in A-779 group lesions were statistically significantly higher. Measured
      by real time RT-PCR relative p22phox (submit of NADPH oxidase) expression was
      significantly decreased in AVE 0991-treated mice. As revealed by flow cytometry,
      the expression of co-stimulatory molecules: CD86, CD80 and CD40 on both dendritic
      cells (CD11c+) and macrophages (F4/80+) was reduced in AVE 0991-treated group,
      which correlated with decreased expression of CD69 activation marker on CD4+T
      cells. In our report we showed the beneficial effect of AVE 0991 on atherogenesis
      in gene-targeted mice.

PMID- 22460465
TI  - The time-dependent alteration of anti-diuretic hormone system in hindlimb
      unloaded rats.
AB  - It is important to understand the mechanism on the fluid shift and volume
      regulation occurring in astronauts after spaceflight for future life in space. In
      the present study, we examined the time-dependent alteration of anti-diuretic
      hormone (ADH) concentrating on the water reabsorption system in hindlimb unloaded
      rats. Male Sprague-Dawley rats were hindlimb unloaded for 1 (HU1), 7(HU7), 14
      days (HU14) or rested in the ground for 3 days after HU14 (HU14+3). The plasma
      ADH and angiotensin II level showed peak value at HU7, and the alterations were
      restored at HU14. However, several serum electrolytes (Na, K, Cl) were not
      changed regardless of HU period. In the immunohistochemical study, we examined
      that ADH and c-Fos immunoreactivities (IR) were maximized at HU7 in the
      paraventricular nucleus (PVN) and supraoptic nucleus (SON). Aquaporin 2 (AQP2) IR
      also was increased in the renal collecting duct for water re-absorption at HU7
      showing a similar pattern with ADH. These results present a series of
      physiological ADH system alteration following to period of hindlimb unloading
      stimulus, indicating that ADH system is activated significantly at HU7. In
      addition, our results suggest that ADH system activation may be involved in anti
      diuretic phenomenon in early spaceflight period. Furthermore, it is speculated
      that ADH system may require 14 days for adaptation to microgravity.

PMID- 22460466
TI  - Influence of tobacco smoke on the pharmacokinetics of citalopram and its
      enantiomers.
AB  - The purpose of this study was to evaluate the influence of tobacco smoke on the
      pharmacokinetics of citalopram (CIT) and desmethylcitalopram (DCIT) and its
      enantiomers on an animal model. High performance liquid chromatography (HPLC)
      with a diode array detector (DAD) was used for the identification and
      quantification of the studied compounds. The HPLC quantification of racemic
      mixtures of CIT was performed on a C18 column. The limits of detection (LOD) and
      quantification (LOQ) were: 7 and 10 ng/ml respectively. HPLC separation of
      citalopram enantiomers (S- and R-CIT) was performed on a Chirobiotic V column.
      The limits of detection (LOD) and quantification (LOQ) were: 6 and 15 ng/ml for R
      and S-CIT respectively. The experiment was carried out on male Wistar rats. The
      rats were exposed to tobacco smoke for five days (6 hours per day). After the
      exposure, citalopram was administered in a dose of 10 mg/kg intragastrically. In
      the control group (non-exposed animals), citalopram was administered in the same
      way and at an equal dose. The blood of the animals was collected at nine time
      points. It was found that tobacco smoke exposure inhibits the biotransformation
      of citalopram. The half-life of the racemic mixture of citalopram after
      intragastric administration was increased by about 287%. Changes in the
      pharmacokinetic parameters of S-citalopram (active isomer) show a similar
      tendency to those of the racemic mixture. The pharmacokinetics of R-citalopram
      showed no statistically important differences after tobacco smoke exposure.
      Alterations in the pharmacological parameters of desmethylcitalopram presented an
      opposite trend to the parent drug. After exposure to tobacco smoke, the induction
      of metabolism of this compound was observed.

PMID- 22460467
TI  - Bioimpedance vector pattern in head and neck squamous cell carcinoma.
AB  - Direct bioimpedance measures (resistance, reactance, phase angle (PA)) determined
      by bioelectrical impedance analysis (BIA) detect changes in tissue electrical
      properties. The study was conducted to evaluate soft tissue hydration and mass
      through pattern analysis of vector plots as height, normalized resistance, and
      reactance measurements by bioelectric impedance vector analysis in patients with
      head and neck cancer. Whole-body measurements were made with ImpediMed
      bioimpedance analysis in 56 adult, white, male subjects 42 to 79 years old: 28
      patients with head and neck squamous cell carcinoma (H&NC) and 28 healthy
      volunteers matched by sex, age and BMI as a control group. All patients were
      previously untreated and without active nutritional interventions. Mean vectors
      of H&NC group vs. the control group were characterized by an increased normalized
      resistance component with a reduced reactance component (separate 95% confidence
      limits, P<0.05), indicating a decreased ionic conduction (dehydration) with loss
      of dielectric mass (cell membranes and tissue interfaces) of soft tissue.
      Monitoring vector displacement trajectory toward the reference target vector
      position may represent useful feedback in support therapy planning of individual
      patients before surgery in patients with head and neck cancer in order to reduce
      post-operational complications.

PMID- 22460468
TI  - Assessment of the innate and adaptive immune system in proliferative
      vitreoretinopathy.
AB  - PURPOSE: Proliferative vitreoretinopathy (PVR) is the leading cause of failure of
      surgery for rhegmatogenous retinal detachment. Although indirect evidence
      suggests that this disease might be autoimmune in nature, direct proof for this
      hypothesis is lacking. The purpose of this study was to determine in a murine
      model whether PVR can develop in the absence of T- or B-cell immunity. METHODS:
      Four- to six-week-old Rag-1 gene knockout (KO) and congenic wild-type mice (WT)
      on the C57.Bl/6 background were studied. PVR was induced by intravitreal
      injection of 3 MUl dispase at the concentration of 0.2 U/MUl. PVR development was
      monitored by electroretinograms, the macroscopic observation of hemorrhage,
      cataract, retinal folds, and of an uneven iris, as well as the histological
      detection of epiretinal membranes on haematoxylin-eosin stained tissue.
      Additionally, immunofluorescence analysis was performed. These manifestations of
      PVR were assessed 1, 2, 4, 6, and 8 weeks after the intravitreal injection.
      RESULTS: The data showed that the immune-deficient Rag-1 KO mice developed PVR
      with similar kinetics and severity as did the fully immune competent congenic WT
      mice. Carboxyfluorescein diacetate succinimidyl ester-labeled T cells that are
      specific for ovalbumin were detected in the inflamed vitreous and retina showing
      that T cells that are not specific for autoantigens present in the eye can
      migrate to PVR lesions. Therefore, the mere presence of T cells in PVR lesions
      does not imply an autoimmune pathogenesis. CONCLUSION: This study suggests that T
      and B-cell immunity is not essential for the induction of PVR.

PMID- 22460469
TI  - Effects of energy restriction and exercise on bone mineral density during
      lactation.
AB  - Modest energy restriction combined with resistance training (RT) has been shown
      in nonlactating women to protect bone during periods of weight loss. However,
      there is a paucity of research on dietary interventions and exercise in lactating
      women aimed at promoting bone health and weight loss. PURPOSE: This study aimed
      to investigate the effects of energy restriction and exercise on bone mineral
      density (BMD) and hormones during lactation. METHODS: At 4 wk postpartum,
      participants were randomized to either a 16-wk intervention (diet restricted by
      500 kcal and RT 3 d.wk) group (IG = 14) or minimal care group (CG = 13).
      Measurements included BMD by DXA, three 24-h dietary recalls, and hormones.
      Repeated-measures ANOVA was used to test for group differences over time.
      RESULTS: Energy intake decreased more in IG (613 +/- 521 kcal) than CG (171 +/-
      435 kcal) (P = 0.03). IG lost more weight (5.8 +/- 3.5 kg vs CG = 1.6 +/- 5.4 kg,
      P = 0.02). BMD decreased over time, P < 0.01, with no group differences in lumbar
      spine (IG = 3.4% +/- 2.5%, CG = 3.7% +/- 3.3%) or hip (IG and CG = 3.1 +/- 1.8%).
      Prolactin and estradiol decreased over time in both groups, P < 0.01. Basal
      growth hormone remained stable; however, there was a significant increase in
      growth hormone response to exercise in IG. CONCLUSIONS: These results suggest
      that moderate energy restriction combined with RT promotes weight loss with no
      adverse effects on BMD during lactation.

PMID- 22460470
TI  - Scheduled exercise phase shifts the circadian clock in skeletal muscle.
AB  - PURPOSE: It has been well established in mammals that circadian behavior as well
      as the molecular clockwork can be synchronized to the light-dark cycle via the
      suprachiasmatic nucleus of the hypothalamus (SCN). In addition to light, it has
      been demonstrated that nonphotic time cues, such as restricting the time of food
      availability, can alter circadian behavior and clock gene expression in selected
      peripheral tissues such as the liver. Studies have also suggested that scheduled
      physical activity (exercise) can alter circadian rhythms in behavior and clock
      gene expression; however, currently, the effects of exercise alone are largely
      unknown and have not been explored in skeletal muscle. METHODS:
      Period2::Luciferase (Per2::Luc) mice were maintained under 12 h of light followed
      by 12 h of darkness then exposed to 2 h of voluntary or involuntary exercise
      during the light phase for 4 wk. Control mice were left in home cages or moved to
      the exercise environment (sham). A second group of mice had restricted access to
      food (4 h . d(-1) for 2 wk) to compare the effects of two nonphotic cues on
      PER2::LUC bioluminescence. Skeletal muscle, lung, and SCN tissue explants were
      cultured for 5-6 d to study molecular rhythms. RESULTS: In the exercised mice,
      the phase of peak PER2::LUC bioluminescence was shifted in the skeletal muscle
      and lung explants but not in the SCN suggesting a specific synchronizing effect
      of exercise on the molecular clockwork in peripheral tissues. CONCLUSIONS: These
      data provide evidence that the molecular circadian clock in peripheral tissues
      can respond to the time of exercise suggesting that physical activity contributes
      important timing information for synchronization of circadian clocks throughout
      the body.

PMID- 22460471
TI  - Frontal plane biomechanics in males and females with and without patellofemoral
      pain.
AB  - PURPOSE: The study's purpose was to compare trunk, pelvis, hip, and knee frontal
      plane biomechanics in males and females with and without patellofemoral pain
      syndrome (PFPS) during stepping. METHODS: Eighty recreational athletes were
      equally divided into four groups: female PFPS, female controls, male PFPS, and
      male controls. Trunk, pelvis, hip, and knee frontal plane kinematics and
      activation of the gluteus medius were evaluated at 15 degrees , 30 degrees , 45
      degrees , and 60 degrees  of knee flexion during the downward and upward phases
      of the stepping task. Isometric hip abductor torque was also evaluated. RESULTS:
      Females showed increased hip adduction and knee abduction at all knee flexion
      angles, greater ipsilateral trunk lean and contralateral pelvic drop from 60
      degrees  of knee flexion till the end of the stepping task (P = 0.027-0.001),
      diminished hip abductor torque (P < 0.001), and increased gluteus medius
      activation than males (P = 0.008-0.001). PFPS subjects presented increased knee
      abduction at all the angles evaluated; greater trunk, pelvis, and hip motion from
      45 degrees  of knee flexion of the downward phase till the end of the maneuver;
      and diminished gluteus medius activation at 60 degrees  of knee flexion, compared
      with controls (P = 0.034-0.001). Females with PFPS showed lower hip abductor
      torque compared with the other groups. CONCLUSIONS: Females presented with
      altered frontal plane biomechanics that may predispose them to knee injury. PFPS
      subjects showed frontal plane biomechanics that could increase the lateral
      patellofemoral joint stress at all the angles evaluated and could increase even
      more from 45 degrees  of knee flexion in the downward phase until the end of the
      maneuver. Hip abductor strengthening and motor control training should be
      considered when treating females with PFPS.

PMID- 22460472
TI  - Short-duration resistive exercise sustains neuromuscular function after bed rest.
AB  - PURPOSE: The study's purpose was to assess the effectiveness of a short-duration
      three-times-weekly high-load resistive exercise program on preventing
      deterioration in neuromuscular function after prolonged bed rest. METHODS: Twenty
      four male subjects performed high-load resistive exercise (n = 8), high-load
      resistive exercise with whole-body vibration (n = 9), or no exercise (control, n
      = 9) during 60-d head-down tilt bed rest as part of the 2nd Berlin Bed Rest
      Study. Peak countermovement jump power and height, sit-to-stand performance,
      sprint time over 15 and 30 m, and leg press one-repetition maximum were measured
      before and after bed rest. RESULTS: The exercise interventions were capable of
      ameliorating losses of peak countermovement jump power (P < 0.001) and height (P
      < 0.001), deterioration of sit-to-stand time from 45-cm (P = 0.034) and 30-cm (P
      < 0.001) sitting positions, increases of 15-m (P = 0.037) and 30-m (P = 0.005)
      sprint time, and losses of leg press one-repetition maximum (P < 0.001).
      CONCLUSIONS: The short-duration (6-min time under tension per training session)
      exercise countermeasure program performed three times a week was capable of
      reducing the effect of prolonged bed rest on many neuromuscular function
      measures.

PMID- 22460473
TI  - Potentiation of maximal voluntary concentric torque in human quadriceps femoris.
AB  - PURPOSE: Previous studies have shown that one bout of 6-s maximal voluntary
      contraction (MVC) can enhance subsequent dynamic joint performance with maximal
      voluntary effort. However, the conditioning contraction also induces central
      fatigue, which attenuates the enhancement of the subsequent voluntary joint
      performance. Here, as a modality for minimizing the fatigue while enhancing joint
      performance, we examined the effects of one bout of a short-duration isometric
      MVC and neuromuscular electrical stimulation (NMES). METHODS: In the first
      experiment, the optimal duration of NMES for inducing twitch potentiation of the
      quadriceps femoris muscle was determined, which was found to be 5 s. Then in the
      second experiment, 13 subjects performed maximal voluntary isokinetic concentric
      knee extensions at 210 degrees  . s(-1) in the following sequence: before and
      immediately after each of the 3-, 5-, and 10-s MVCs and 5-s NMES of knee
      extension and 1, 3, and 5 min thereafter. RESULTS: When the isometric MVC was
      used as a conditioning contraction, the maximal voluntary concentric torque was
      significantly enhanced at 1 and 3 min after MVC only in the 5-s MVC trial (106.6%
      +/- 2.3% and 107.2% +/- 2.6% of the initial value, respectively) but not in the 3
      and 10-s MVC trials. In the 5-s NMES trial, the voluntary concentric torque was
      significantly increased immediately after the conditioning contraction (105.1% +/
      2.2%) as well as 1 and 3 min thereafter (107.5% +/- 3.3% and 107.8% +/- 2.7%,
      respectively). CONCLUSIONS: These results suggest that conditioning contraction
      of around 5 s, performed with isometric MVC or NMES, can be a modality to enhance
      dynamic voluntary joint performance, with the latter having a more immediate
      effect.

PMID- 22460474
TI  - Whey protein does not enhance the adaptations to elbow flexor resistance
      training.
AB  - PURPOSE: It is unclear whether protein supplementation augments the gains in
      muscle strength and size observed after resistance training (RT) because
      limitations to previous studies include small cohorts, imprecise measures of
      muscle size and strength, and no control of prior exercise or habitual protein
      intake. We aimed to determine whether whey protein supplementation affected RT
      induced changes in elbow flexor muscle strength and size. METHODS: We pair
      matched 33 previously untrained, healthy young men for their habitual protein
      intake and strength response to 3-wk RT without nutritional supplementation
      (followed by 6 wk of no training) and then randomly assigned them to protein
      (PRO, n = 17) or placebo (PLA, n = 16) groups. Participants subsequently
      performed elbow flexor RT 3 d . wk(-1) for 12 wk and consumed PRO or PLA
      immediately before and after each training session. We assessed elbow flexor
      muscle strength (unilateral 1-repetition maximum and isometric maximum voluntary
      force) and size (total volume and maximum anatomical cross-sectional area
      determined with magnetic resonance imaging) before and after the 12-wk RT.
      RESULTS: PRO and PLA demonstrated similar increases in muscle volume (PRO 17.0%
      +/- 7.1% vs PLA 14.9% +/- 4.6%, P = 0.32), anatomical cross-sectional area (PRO
      16.2% +/- 7.1% vs PLA 15.6% +/- 4.4%, P = 0.80), 1-repetition maximum (PRO 41.8%
      +/- 21.2% vs PLA 41.4% +/- 19.9%, P = 0.97), and maximum voluntary force (PRO
      12.0% +/- 9.9% vs PLA 14.5% +/- 8.3%, P = 0.43). CONCLUSIONS: In the context of
      this study, protein supplementation did not augment elbow flexor muscle strength
      and size changes that occurred after 12 wk of RT.

PMID- 22460475
TI  - Aerobic exercise alters skeletal muscle molecular responses to resistance
      exercise.
AB  - PURPOSE: This study assessed the influence of an acute aerobic exercise bout on
      molecular responses to subsequent resistance exercise (RE). METHODS: Nine
      physically active men performed a 45-min one-legged cycle ergometry exercise and
      4 * 7 maximal concentric-eccentric knee extensions for each leg 6 h later. Thus,
      one limb was subjected to aerobic and resistance exercise (AE+RE), and the
      contralateral limb to resistance exercise (RE) only. Knee extensor peak power was
      determined. Biopsies were obtained from the m vastus lateralis before (PRE) and
      15 min (POST1) and 3 h after RE. Analysis determined glycogen content, mRNA
      levels (vascular endothelial growth factor, peroxisome proliferator-activated
      receptor-gamma coactivator-1, muscle RING-finger protein-1, atrogin-1,
      myostatin), and phosphorylated proteins (mammalian target of rapamycin, p70S6
      kinase, ribosomal protein S6, eukaryotic elongation factor 2). RESULTS: Peak
      power was similar in AE + RE and RE. After RE, the time course of glycogen
      utilization and protein signaling was similar across legs. However,
      phosphorylation of mammalian target of rapamycin and p70S6 kinase was elevated in
      AE + RE versus RE (main effect, P < 0.05). Vascular endothelial growth factor and
      peroxisome proliferator-activated receptor-gamma coactivator-1 were higher in AE
      + RE than in RE at PRE and POST1 (P < 0.05). Myostatin was lower in AE + RE
      versus RE at PRE and POST1 (P < 0.05) and downregulated after resistance exercise
      only. Atrogin-1 was higher in AE + RE than in RE at PRE and POST1 (P < 0.05) and
      decreased after RE in AE + RE. Muscle RING-finger protein-1 was similar across
      legs. No difference for any marker was evident 3 h after RE. CONCLUSIONS: These
      results suggest that acute aerobic exercise alters molecular events regulating
      muscle protein turnover during the early recovery period from subsequent RE.

PMID- 22460477
TI  - Effects of acute resistance exercise on late-middle-age adults' goal planning.
AB  - PURPOSE: We investigated the effects of an acute bout of resistance exercise on
      the planning component of executive function in late-middle-age adults. METHODS:
      With a within-subjects design, 30 community-dwelling adults (mean age = 57.20 +/-
      2.93 yr, 16 females) experienced both resistance exercise and control treatment
      conditions. The exercise condition involved two sets of 10 repetitions of 70% of
      10-repetition maximum of seven exercises, whereas the control condition consisted
      of reading. Planning was assessed before and immediately after each treatment via
      the Tower of London task. RESULTS: Acute resistance exercise facilitated Tower of
      London performances in terms of less total move scores, more total correct
      scores, and a longer total initial time compared with control and baseline.
      CONCLUSIONS: Our results expand the existing literature by demonstrating that
      resistance exercise has a positive effect on cognition and contributes to
      improved quality of planning, working memory, and inhibition aspects of executive
      function.

PMID- 22460476
TI  - Exercise training improves plantar flexor muscle function in mdx mice.
AB  - PURPOSE: We tested the hypothesis that low-intensity exercise in mdx mice
      improves plantar flexor muscle contractile function, resistance to fatigue, and
      mitochondrial adaptations without exacerbating muscular dystrophy. METHODS: We
      subjected mdx mice to 12 wk of voluntary low-resistance wheel running (Run, n =
      17) or normal cage activities (sedentary (Sed), n = 16) followed by in vivo
      analyses for plantar flexor torque generation and fatigue resistance or running
      capacity on a treadmill. Gastrocnemius muscles were further evaluated for
      exercise-induced mitochondrial adaptations and fiber type distribution and
      central nuclei. t-tests were used to determine differences between the Sed and
      Run groups. RESULTS: Plantar flexor submaximal isometric torques and maximal
      isometric torque at multiple ankle joint angles and resistance to fatigue were
      greater in Run compared with Sed mdx mice (P G 0.05). Citrate synthase and A
      hydroxyacyl-CoA dehydrogenase enzyme activities and cytochrome c oxidase IV
      protein expression in gastrocnemius muscles were greater in Run than in Sed mdx
      mice(P e 0.04), along with a trend of fiber type transformation from Type IIb to
      Type IIx fibers. Exercise training in mdx mice did not elevate serum creatine
      kinase levels but led to a significant reduction of centrally nucleated
      myofibers. CONCLUSIONS: Voluntary low-resistance wheel running in mdx mice can
      result in skeletal muscle adaptation, leading to improved contractile function
      and reduced fatigability,with no indication that exercise was detrimental. This
      study supports the need for further investigation of low-intensity exercise as an
      early therapeutic intervention in ambulatory boys with Duchenne muscular
      dystrophy.

PMID- 22460479
TI  - Embodying 'health citizenship' in health knowledge to fight health inequalities.
AB  - This paper wishes to contribute to the debate around citizen participation in
      health system decision-making that has been present internationally for the last
      30 years. I argue that if we aim to change health inequalities, health
      professionals and planners need to understand the illness and health service
      experience of citizens. The concept of 'health citizenship' introduced here
      refers to health knowledge that integrates the lay knowledge of patients and that
      this integration is translated into health actions such as clinical communication
      and the planning of health care, programs, and policy. We illustrate our argument
      with the two cases: health literacy and the promotion of breastfeeding in a
      Canadian population living in context of poverty. This paper then concludes by
      addressing the leadership role, Brazilian graduate nursing schools can play in
      promoting 'health citizenship' and by doing so, contribute to fight health
      inequalities.

PMID- 22460480
TI  - [Touching the premature: the meaning for nurse's aides and technicians].
AB  - This study aimed to understand the meaning of touching the premature, in the
      nursing care, for nursing aides and technicians. The Symbolic Interaction was
      used as theoretical reference and the Grounded Theory as methodological
      reference. Data were collected through observation and semi-structured
      interviews, carried out with three nursing aides and two technicians. Data
      analysis was carried out until leading to the identification of the conceptual
      category Enhancing the baby's welfare and care through touch, representing the
      meaning of touching the premature for the nursing aides and technicians, who
      consider touch as the basis of caring, recognising it as part of the daily care
      and performing the action of touching as a way to enhance the baby's welfare.

PMID- 22460481
TI  - [Humanized attention to parturition of adolescents: analysis of practices
      developed in an obstetric center].
AB  - Quantitative study that aimed to analyze the practices developed in assisting the
      adolescent, from the account of health workers, in an Obstetric Center in a
      teaching hospital, based on the proposal of humanization of parturition of the
      Health Ministry. According to the workers, useful practices in assisting
      parturition, among them, orientations about relaxation techniques at parturition,
      improving the attachment between mother and child, are being carried out.
      However, the right to a companion has not been taken into account. The lithotomy
      position and standardization of trichotomy, episiotomy e amniotomy were
      registered. Medical records, among them partogram, anamnesis and physical and
      obstetric exam of the parturient, proved to the unsatisfactory. We conclude that,
      in the scenario investigated, are developed practices considered appropriate and
      inappropriate, showing the need to further encourage the use of procedures
      grounded in scientific evidence and inserted into the proposal to the
      humanization of birth.

PMID- 22460482
TI  - Suicide attempts by exogenous intoxication among female adolescents treated at a
      reference hospital in the City of Recife-PE, Brazil.
AB  - This study aimed to assess cases of self-inflicted poisoning among adolescents
      reported by the Toxicological Care Center of a reference hospital in Recife-PE,
      Brazil. The data were collected between March and May 2010 from hospital charts
      and structured interviews with the participants and parents/guardians. Among the
      25 cases of attempted suicide registered in the period, 21 were female
      adolescents, who made up the sample of the present study. The adolescents were
      between 13 and 19 years of age. Pesticides were the most frequent toxic agent
      used (61.9%). The results of the present study underscore the importance of
      studying suicide in this population, with a focus on family relations, in order
      to lay the foundation for the development of prevention and treatment programs
      for this vulnerable group.

PMID- 22460483
TI  - [Perceptions and changes in the quality of life of patients submitted to
      hemodyalisis].
AB  - Chronicle Renal Failure is considered a major problem in Public Health. The
      dyalitic treatment while waiting for the renal transplant means a boost on
      quality of life. This qualitative study, carried out in Rio Grande-RS, aimed at
      knowing the perceptions of patients with Chronicle Renal Failure, identifying the
      elements that influence their quality of life. The results highlighted that the
      initial feelings of indignation and denial change as they strengthen themselves
      to face the disease. Restrictions of fluid and eating habits, inability to
      perform or limitation in activities, professional and leisure, were the main
      difficulties identified. The support from family members and from health
      professionals may help to overcome these limitations and adaptation to a new
      lifestyle.

PMID- 22460484
TI  - [Impact of monocular vision after ocular trauma].
AB  - Convergent-care qualitative research, that aimed to identify perceptions and
      meanings related to visual loss in patients with monocular vision due to ocular
      trauma. Participants were six victims of ocular trauma with monocular vision,
      from a reference hospital in emergency. Data emerged from the speeches of people
      in the living group and from semi-structured interviews. The results showed the
      expectative to see again, the doubt on the diagnosis and lack of monitoring,
      which arouse the feeling of anguish and conflict situation related to loss of
      independence. The living group was considered a contributor to a healthier life
      by promoting the exchange of experiences and knowledge.

PMID- 22460485
TI  - [The social network as a health support strategy for hypertensive patients].
AB  - The social network has positive influence on people's health and well-being and
      this theme has been widely debated over the past decades. This is a qualitative
      study including twenty hypertensive patients aged 50 to 80 years old, living in
      Maringa-PR. The study aimed to identify which individuals, who belong to the
      hypertensive patients' social network, are considered as support or help to them
      during their disease and treatment. Results pointed the family network as the
      most representative in the patient's support, mainly regarding nutrition and
      medicine use. The doctor was the health professional most remembered by this
      population, and his/her role was restricted to drugs prescription. We highlight
      the importance of the social network to hypertensive patients as a strategy to
      improve their quality of life.

PMID- 22460486
TI  - [Heart failure: strategies used by elders in search for quality of life].
AB  - This is a descriptive study, with qualitative approach, aiming to identify the
      repercussions of heart failure on elders' quality of life; to describe the
      strategies used in facing these repercussions and, understand the perceptions of
      nursing care. Semi-structured interviews were carried out with ten elders holding
      heart insufficiency at a military hospital in Rio de Janeiro-RJ. It was
      identified that heart failure generates emotional, physical and financial
      repercussions in the elders' lives, provoking impact on their quality of life.
      Among the strategies created by the elders, it was noticed the palliative coping
      and the emotional conflict. The nursing cares noticed were orientation,
      affection, goodwill and dedication. To take care of the elders holding heart
      failure implies in evaluating repercussions in their functional capacity and
      autonomy, requiring capacities and competencies of the nurses to identify their
      specificities in the perspective of a whole care that contributes to the elders'
      quality of life.

PMID- 22460487
TI  - [Mortality associated with nosocomial infection, occurring in a general hospital
      of Sumare-SP, Brazil].
AB  - This study investigated the socio-demographic profile, clinical procedures and
      etiology of nosocomial infection associated with deaths in the Hospital Estadual
      Sumare, state of Sao Paulo, Brazil, from 2007 to 2008. The retrospective study of
      medical records (n = 133) revealed an average of 35 days of hospitalization. Most
      patients (97%) underwent some invasive procedure associated with nosocomial
      infection (p <= 0.05), including: 90 (67.7%) pneumonia, 62 (46.6%), urinary
      infections and 97 (73%) septicemia. Infection was the leading cause of death in
      75 (56.4%) cases, with defined etiology in 110 (82.7%); 34 (30.9%) because of
      microorganisms that were multidrug-resistant. The most common was Staphylococcus
      aureus (25%), related to pneumonia and blood stream infection. The monitoring of
      hospital infection contributed to intervention at risk situation and death.

PMID- 22460488
TI  - [Evaluation of antimicrobial activity antiseptics and disinfectants used in a
      public health service].
AB  - The study aimed to determine the in vitro antimicrobial activity of antiseptics
      and disinfectant used in the care service primary health of a city in northern
      Parana, using microorganisms standardized by the National Institute of Quality
      Control in Health, Oswaldo Cruz Foundation. For this purpose, we performed tests
      of antimicrobial activity and chemical stability of three samples of antiseptic
      and one disinfectant used in the service. From the analysis performed the first,
      seventh, fourteenth and twenty-first day after the opening of the bottles, it was
      found that the samples retained their activity in vitro antimicrobial regarding
      standardized strains, as evidenced by the absence of growth of colony-forming
      units and maintaining the chemical stability. The study demonstrated the efficacy
      of the samples against analysis microbiological in vitro using standardized
      microorganisms.

PMID- 22460489
TI  - [Ecological care as a broad and complex phenomenon].
AB  - This study aimed to comprehending the meaning of ecological care from the point
      of view of students and teachers of the health area of a Public Institution of
      Higher Education. It was an exploratory qualitative research conducted by the
      method of the Theory Based on the Data, for which ten in depth interviews were
      carried out between September/2008 and April/2009, distributed in two sample
      groups. The process of data collection and analysis culminated with the
      formulation of the theory "Viewing ecological care as a broad and complex
      phenomenon", which was discussed through the view of complexity. One concluded
      that the academic environment is constituted by an appropriate space for the
      development of the systemic abilities, capable of contemplating the relations,
      interactions and necessary associations for the comprehension and promotion of
      the environmental sustainability.

PMID- 22460490
TI  - [Validation of standard operating procedures in nursing care of patients with
      totally implanted catheters].
AB  - Care protocols are important technological resources in health practice and
      should be validated for the sake of scientific credibility in professional
      practice. This research aimed to validate the items of the proposed standard
      operating procedures (SOPs) related to access, heparinization and dressing of
      totally implanted catheters, using concept analysis as proposed by Hoskins. The
      study involved two phases. In the first, a form was elaborated to validate the
      SOPs. In the second, the SOPs contents were subject to expert validation.
      Suggestions addressed aspects like reformulations, adding actions to make them
      clearer and more comprehensive, the order of procedure steps and the material to
      adapt the instrument. Further research is needed to orient professionals, mainly
      regarding the heparinization of catheters and the first dressing change after the
      access, with a view to standardizing conducts based on safe scientific evidence.

PMID- 22460491
TI  - [Unveiling the knowing/doing on nursing diagnosis: experience in neurosurgical
      oncology].
AB  - Article extracted from a Master's dissertation whose objective was to
      characterize the interaction of nurses with nursing diagnoses in neurosurgical
      oncology, considering behaviors, expressions, attitudes and practices. The
      participants were sixteen nurses who work with equal or more than five years in
      neurosurgical oncology at the National Cancer Institute. The Symbolic
      Interactionism was used as the theoretical framework, and the Grounded Theory, as
      a methodological approach. The findings indicate that the nurse is unveiling
      possibilities of caring for the client of neurosurgical oncology, not only in the
      perspective of suffering, but especially from the perspective of existential
      care, covering their needs and singularities, and respecting their limitations.

PMID- 22460492
TI  - [Implications of nursing staff's dimensioning in the accomplishment of
      professional nurse's competences].
AB  - This exploratory-descriptive study aimed to measure and evaluate the adequacy of
      the professional nursing staff in a university hospital, and to reflect on the
      implications of personnel dimensioning in the performance of nurses'
      responsibilities. It was calculated the daily classification of patients, using
      appropriate instrument, and then it was applied the methodology proposed by
      Resolution No 293/2004 of the Federal Council of Nursing, enabling discussion of
      institutional reality. It was verified an inadequacy in the quantitative of the
      nurses category, and the need to sensitize the multidisciplinary team to adopt a
      working methodology that provides quality care. It is emphasized that the
      personnel dimensioning creates direct implications on the performance of nurses'
      responsibilities; therefore, an inappropriate personnel dimensioning results in
      loss in quality of care.

PMID- 22460493
TI  - [Management of nursing personnel with job security: perceptions of nurses].
AB  - This study aimed to identify a university hospital nurses' perception on the
      management of nursing personnel with job security, using data collected from a
      qualitative research developed with sixteen nurses, in 2010. The data, collected
      through semi-structured interviews, and analyzed by Thematic Analysis, produced
      two empirical categories: Security at work versus the impunity afforded by
      tenure; Job stability and (un)involvement in nursing work. It has been verified
      that job stability provides security of employment; security spawns impunity, and
      nurses are reluctant to conduct administrative proceedings. The conclusion are
      that the security of employment caused by stability can favour the break of
      hierarchies; impunity leads to the vulgarisation of transgressions by the lack of
      effective administrative measures toward the solution of problems; and job
      stability does not ensure the quality of assistance.

PMID- 22460494
TI  - [Eating habits in the first year of life].
AB  - The study aimed to examine the relevant published literature to food practices in
      the first year of life of teenage mothers' children, through an integrative
      review within Lilacs, Medline and Cochrane, databases from 2000 to 2010. We used
      the keywords: adolescent, breastfeeding, mixed feeding and infant nutrition, from
      which we selected eleven articles that composed the study sample. The results
      indicated the paucity of published research on the proposed topic, especially for
      those focusing on complementary feeding, revealing a gap in global production on
      the subject. New researches, therefore, need to be developed with a focus on
      teenage mothers, exploring infant feeding in all its dimensions.

PMID- 22460496
TI  - [Illness perception: an evaluation to be conducted by nurses].
AB  - Illness perception is understood as the way individuals understand and cope with
      their disease. The objective of this paper was to identify articles in literature
      developed by nurses on disease perception, and the instruments available to
      assess it. An integrative literature review was performed, which identified nine
      papers that related to the perception of the disease with Health Education,
      Coping, Treatment adherence and quality of life. Ways of assessing this
      phenomenon were also identified. It was concluded that nurses should periodically
      assess the perception of illness by validated instruments, along with the use of
      nursing diagnoses reported by NANDA International (NANDA-I).

PMID- 22460495
TI  - [Nursing actions face to sexual violence against children and adolescents].
AB  - The objective of this work was to think over the sexual violence against children
      and adolescents, focusing on the nurses' performance regarding their professional
      practice and Brazilian legislation. This is a bibliographical study in which 31
      publications covering the period from 2005 until 2008 were researched. Through
      content analysis, thematic modality, the knowledge characterization was obtained
      in three cores: attention towards children and adolescents' health, notification
      and professional qualifications. The nurse must be able to care of children and
      adolescents based on the laws that protect them, being an imperative for that the
      involvement of health services, class entities and universities.

PMID- 22460497
TI  - [Nursing audit: systematic review of the literature].
AB  - This study aimed to analyze the scientific production about audit in nursing,
      published in national papers, between 1998 and 2008. A systematic review of the
      literature was conducted, with articles being searched in the databases LILACS
      and SciELO, from the key words: audit, nursing, quality health care and nursing
      supervision. The sample consisted of ten works. The analyzed publications
      describe the main distortions and non-conformities found in nursing records,
      relating them mainly with the quality of nursing care and with the financial
      damage to the institutions. The publications also include the administrative role
      of the nurse, especially her/his leadership role in the team of nursing; and
      nursing audit as an educational process.

PMID- 22460498
TI  - [Core sets of the International Classification of Functioning, Disability and
      Health].
AB  - The International Classification of Functioning, Disability and Health (ICF)
      offers a model of human functioning that integrates biomedical, social and
      personal aspects, and standardize the terminology that describes disabling
      conditions related to health. However, because of its complexity and large number
      of aspects to be covered, the development of practical ICF-based tools was
      needed. ICF core sets are collections of ICF categories that describe functioning
      of people with determined health conditions. They have been developed in
      consensus processes with multiprofessional and international representation. They
      can be either brief or comprehensive, according to its use by one or more
      professionals. Their use allows clinicians to assess aspects that are not cared
      about by any other evaluation tool, like environmental factors.

PMID- 22460499
TI  - [The social representations theory in Brazilian nursing research].
AB  - This study aimed to examine methodological issues in the theses and dissertations
      that used social representations theory (SRT) in Brazilian nursing. Twenty-two
      dissertations and 44 theses were considered. Categorical content analysis was
      applied, based on five aspects: objects studied, place of SRT, the number of
      study participants, data collection techniques and data analysis. The
      predominance of case studies and use, especially of semi-structured interviews,
      although relevant to the study of SR, do not sufficiently consider the extent of
      suck knowledge sharing in society. One must take into account lay knowledge to
      understand health care contextualized studies on health care.

PMID- 22460500
TI  - [Public policy and rights of Single Health System's users with diabetes
      mellitus].
AB  - This study approaches the relationship between public policies and the rights of
      SUS (Single Health System) users with diabetes mellitus regarding the supplies
      used in the treatment of diabetes, under the view of legal rules and procedures
      for support of this population. Health professionals should be a link between
      users and current health model, actively assuming a role of defending the rights
      of SUS users with diabetes mellitus. This posture is an ideal to be achieved and
      consolidated in daily practices. The educational process needs to be
      strengthened, including the ethical-political dimension during actions
      implemented with SUS users.

PMID- 22460501
TI  - [Reflections on the care of nursing and the autonomy of the human being under the
      condition of hospitalized elderly].
AB  - There has been an increase of chronic diseases with the subsequent need for care
      and hospitalization, due to the acceleration of the elderly demographic growth.
      The objective of the present paper is to reflect on the care of nursing and the
      autonomy of the human being under the condition of elderly hospitalization.
      Nursing professionals, caring in the hospital ambient, can contribute
      significantly for the construction of the elderly autonomy and participation on
      the decision making about their need for attention or health care. The ethics
      redeeming, under a worthy aging perspective, permeates several discussions in the
      aging society and, specifically, among health professionals who act in hospital
      institutions.

PMID- 22460503
TI  - [Training of community health workers: experience of teaching and practice with
      nursing students].
AB  - This paper aims to report an experience carried out by nursing students from the
      Undergraduate School of Health Sciences, Federal District, during their first
      year of study. The objective was to implement a training for 22 community health
      workers, in order to clarify them about their role in community work and to
      elevate their self esteem. A methodology of problematization and various
      educational techniques were used. The themes were: duties and rights,
      responsibilities, communication, ethics, team work, children's health, care for
      the elderly and domestic violence. The result was considered positive for both
      sides: the community workers acquired new knowledge/capabilities and better
      feeling of self worth and the students were able to integrate theory and practice
      and become active participants in the learning process.

PMID- 22460502
TI  - [Application of concept map for the identification of nursing diagnosis].
AB  - This is an experience report, aiming at describing the application of the Concept
      Map as a strategy to develop critical thinking skills in the identification of
      priority nursing diagnoses in a clinical situation. An elaborated fictitious
      clinical case and the concept map, created by using the IHMC CmapTools computer
      program, are presented. It was concluded that the use of Concept Map to identify
      the nursing diagnoses led to the development of critical thinking skills;
      therefore, its use should be stimulated during the academic program.

PMID- 22460504
TI  - Early-phase occurrence of K+ and Cl- efflux in addition to Ca 2+ mobilization is
      a prerequisite to apoptosis in HeLa cells.
AB  - Sustained rise in cytosolic Ca(2+) and cell shrinkage mainly caused by K(+) and
      Cl(-) efflux are known to be prerequisites to apoptotic cell death. Here, we
      investigated how the efflux of K(+) and Cl(-) as well as the rise in cytosolic
      Ca(2+) occur prior to caspase activation and are coupled to each other in
      apoptotic human epithelial HeLa cells. Caspase-3 activation and DNA laddering
      induced by staurosporine were abolished by blockers of K(+) and Cl(-) channels or
      cytosolic Ca(2+) chelation. Staurosporine induced decreases in the intracellular
      free K(+) and Cl(-) concentrations ([K(+)](i) and [Cl(-)](i)) in an early stage
      prior to caspase-3 activation. Staurosporine also induced a long-lasting rise in
      the cytosolic free Ca(2+) concentration. The early-phase decreases in [K(+)](i)
      and [Cl(-)](i) were completely prevented by a blocker of K(+) or Cl(-) channel,
      but were not affected by cytosolic Ca(2+) chelation. By contrast, the Ca(2+)
      response was abolished by a blocker of K(+) or Cl(-) channel. Strong hypertonic
      stress promptly induced a cytosolic Ca(2+) increase lasting >50 min together with
      sustained shrinkage and thereafter caspase-3 activation after 4 h. The hypertonic
      stress induced slight increases in [K(+)](i) and [Cl(-)](i) in the first 50 min,
      but these increases were much less than the effect of shrinkage-induced
      condensation, indicating that K(+) and Cl(-) efflux took place. Hypertonicity
      induced caspase-3 activation that was prevented not only by cytosolic Ca(2+)
      chelation but also by K(+) and Cl(-) channel blockers. Thus, it is concluded that
      not only Ca(2+) mobilization but early-phase efflux of K(+) and Cl(-) are
      required for caspase activation, and Ca(2+) mobilization is a downstream and
      resultant event of cell shrinkage in both staurosporine- and hypertonicity
      induced apoptosis.

PMID- 22460506
TI  - [Locomotive syndrome and frailty. Frail elderly].
AB  - Frailty is a concept born in the mid 1980s, toward which a disease-oriented
      approach has turned to functional assessment. The domain of frailty contains the
      weakness of muscle strength, mental problems and social solitude. Fall is a good
      clinical indicator for the weakness of muscle strength as well as neuro-mental
      problems. Two topics in this review are; (1) Sex difference of hip fracture in
      relation with the sex difference of fall risks. Especially I will focus on the
      postural changes with osteoporosis as risks for falls. (2) Multiple geriatric
      conditions and brain white matter lesion. These conditions include falls,
      tripping, urinary frequency, urinary incontinence, body weight loss and
      swallowing disturbance, which are frequently observed in frail elderly persons.

PMID- 22460505
TI  - Thioridazine induces apoptosis by targeting the PI3K/Akt/mTOR pathway in cervical
      and endometrial cancer cells.
AB  - Recently, thioridazine (10-[2-(1-methyl-2-piperidyl) ethyl]-2
      methylthiophenothiazine), a well-known anti-psychotic agent was found to have
      anti-cancer activity in cancer cells. However, the molecular mechanism of the
      agent in cellular signal pathways has not been well defined. Thioridazine
      significantly increased early- and late-stage apoptotic fraction in cervical and
      endometrial cancer cells, suggesting that suppression of cell growth by
      thioridazine was due to the induction of apoptosis. Cell cycle analysis indicated
      thioridazine induced the down-regulation of cyclin D1, cyclin A and CDK4, and the
      induction of p21 and p27, a cyclin-dependent kinase inhibitor. Additionally, we
      compared the influence of thioridazine with cisplatin used as a control, and
      similar patterns between the two drugs were observed in cervical and endometrial
      cancer cell lines. Furthermore, as expected, thioridazine successfully inhibited
      phosphorylation of Akt, phosphorylation of 4E-BP1 and phosphorylation of p70S6K,
      which is one of the best characterized targets of the mTOR complex cascade. These
      results suggest that thioridazine effectively suppresses tumor growth activity by
      targeting the PI3K/Akt/mTOR/p70S6K signaling pathway.

PMID- 22460507
TI  - [Locomotive syndrome and frailty. Locomotive Syndrome in the super-aged society].
AB  - Japan has already rushed in the Super-aged society, and up to 5 million aged
      people presumably are under the support-demanding condition. In 2007, Japanese
      Orthopedic Association advocated the new concept "Locomotive Syndrome" in order
      to make all the nation people realize an importance of locomotive organ. "Locomo
      Index 25" is a newly developed questionnaire to evaluate locomotive function,
      consisted of 25 questions. Nation-wide surveillance with this questionnaire would
      be effective in early detection of Locomotive Syndrome.

PMID- 22460508
TI  - [Locomotive syndrome and frailty. Frailty in patients with fall & fall-related
      fracture].
AB  - Among geriatric syndromes, fall and fall-related fractures are one of the leading
      causes of the elderly's need for long-term care. Hip fractures are the typical
      cases. The underlying diseases of locomotive syndrome, such as sarcopenia,
      musculoskeletal ambulation disorder symptom complex, and osteoporosis, are
      closely associated with fall and fall-related fractures. From the stand point of
      frailty, sarcopenia, which is considered the major cause of aging-associated
      declines in function and reserve across multiple physiologic systems, plays a
      role in fall and fall-related fractures. The common adverse health outcomes both
      in locomotive syndrome and frailty, is a decrease in walking function and muscle
      strength. Understanding the role of the underlying diseases of locomotive
      syndrome including osteoarthritis, osteoporosis within the frailty cycle is
      important for the future.

PMID- 22460509
TI  - [Locomotive syndrome and frailty. Musculoskeletal ambulation disorder symptom
      complex and locomotive syndrome].
AB  - Musculoskeletal ambulation disorder symptom complex is the new concept of
      musculoskeletal disorders with disability in walking and balance, which lead to
      the high risk of fall and lower activity in elderly. Locomotive syndrome is
      another concept to aware of healthy locomotive organ for early prevention of
      orthopedic disease.

PMID- 22460510
TI  - [Locomotive syndrome and frailty. Osteoporosis as an underlying disorder in the
      locomotive syndrome].
AB  - Osteoporosis, a disorder related to locomotive syndrome, has been nicknamed "the
      silent disease" since it has no symptoms until fragility fracture occurs.
      However, a new fragility fracture cannot only reduce daily activity but can also
      increase fracture risk resulting in possible repetition of the fracture or other
      new fractures. As a result, daily living activities requiring mobility are often
      rapidly reduced and the quality of life can be considerably impaired. There are
      three strategies for preventing fragility fractures : prevention of falls, anti
      osteoporosis treatment and hip protectors. A multidisciplinary approach including
      these strategies should be emphasized to impede the damaging process involved in
      fragility fracture.

PMID- 22460511
TI  - [Locomotive syndrome and frailty. Locomotive syndrome due to the underlying
      disease of degenerative arthritis].
AB  - Japan became a superaging society. We have been putting a new focus on locomotive
      syndrome and frailty. The prevention and treatment of locomotive syndromes, such
      as osteoarthritis, degenerative spondylosis, lumbar canal stenosis, osteoporosis,
      upper extremity diseases, rheumatoid arthritis, and many other disorders of the
      locomotive organs are important. Because, the locomotive syndrome results in
      deterioration of the exercise function and loss of mental and physical health.
      The aim of locomotive syndrome exercises are: to reduce pain, to restore and
      improve joint function. We need to take a comprehensive approach to locomotive
      syndrome, including lifestyle modification, muscle exercise, stretching and
      therapeutic exercise.

PMID- 22460512
TI  - [Locomotive syndrome and frailty. Lumbar canal stenosis as an underlying disorder
      in the locomotive syndrome].
AB  - Lumbar canal stenosis most commonly affects the elderly population by entrapment
      of the cauda equine roots surrounding the spinal canal often associated with pain
      in the back and lower extremities, difficulty ambulating. The locomotive syndrome
      refers to high-risk conditions under requiring care services, and lumbar canal
      stenosis is an important underlying disease. As one of the key capacities of
      frailty identified muscluloskeletal function, the locomotive syndrome is
      considered to musculoskeletal frail syndrome. Surgical treatment should be
      recommended to take the pressure off the nerves in the lumbar spine when the
      conservative treatments failed, and several studies revealed that the surgery
      generally resulted in a preferable outcome in the lumbar canal stenosis patients.
      Among lumbar canal stenosis patients treated with surgery, locomotive syndrome
      was contained 44% and many of which were seen in thin females. The patients with
      locomotive syndrome had lower muscle volume both in the extremities and the trunk
      than those without locomotive syndrome, and surgical results were poorer in the
      activity of daily life whereas the pain relief was adequately obtained. Treatment
      of the lumbar canal stenosis should be attended to locomotive frailty, and muscle
      strengthening training should be incorporated into pre and postoperative therapy.

PMID- 22460513
TI  - [Sarcopenia in relation to locomotive syndrome and frailty].
AB  - One of the features of a change in our body composition with aging is a loss of
      muscle mass, which is called "sarcopenia" . This change may lead seniors to be
      dependent anothers for some activities in their daily lives. Although sarcopenia
      was primarily defined as a loss of muscle mass with aging, the definition has
      been changing and evolving to include either muscle weakness or decreased muscle
      performance with low muscle mass to attach greater importance to practical
      functions. Sarcopenia is thought to be one of the core features of frail status
      and also one of the causal diseases of locomotive syndrome which was proposed by
      the Japanese Orthopaedic Association in 2007. In our preliminary study,
      sarcopenia was related to a decreased sense of balance and the incidence of
      sarcopenia was higher in frailer seniors.

PMID- 22460514
TI  - [Locomotive syndrome and frailty. Recent advances in sarcopenia research].
AB  - Recently, the European Working Group on Sarcopenia in Older People (EWGSOP) has
      developed a practical definition of sarcopenia, which is the presence of both low
      muscle mass + low muscle function (strength or performance) . Several studies
      have shown that sarcopenia might result from low levels of testosterone or
      vitamin D. Aging-associated chronic inflammation also plays a role. However,
      effective treatment for sacropenia has not been established so far, thus further
      basic and clinical studies are essential.

PMID- 22460515
TI  - [Vitamin D in relation to frailty and locomotive syndrome].
AB  - Frailty is an extremely common and serious health problem in the elderly. Frailty
      has been described as "a biologic syndrome of decreased reserve and resistance to
      stressors, resulting from cumulative declines across multiple physiologic systems
      and causing vulnerability to adverse health outcomes" by Fried and colleagues.
      Frailty is associated with incident falls, functional limitation, disability, and
      mortality. There are many reports that vitamin D deficiency may play roles in
      diabetes mellitus, cancers, multiple sclerosis, and other autoimmune diseases,
      and was associated with poorer physical performance, falls and fractures, and a
      greater risk of nursing home admission. Recently, researches suggest that vitamin
      D may provide treatment and prevention from these diseases lead to frailty.
      Vitamin D is expected to be a treatment for frailty in an aging society.

PMID- 22460516
TI  - [Locomotive syndrome and frailty. Concepts and methods of locomotion training].
AB  - Locomotive syndrome means a condition of need for long-term care or a condition
      at the possible risk of it, due to weakening of locomotive organs, which is, in
      other words, frailty of mobility. Locomotion training is all exercises that help
      prevention or remediation from locomotive syndrome and the centerpieces of them
      consist of squats and single-leg standing exercises. This article explains the
      concepts of locomotion training and the actual manual of those two exercises. It
      will greatly help instructing patients or many other old people in communities or
      care facilities.

PMID- 22460517
TI  - [Locomotive syndrome and frailty. Spine surgery for elderly patients with lumbar
      spinal stenosis].
AB  - The patients with lumbar spinal stenosis do not automatically deteriorate and
      will remain unchanged or even improved by conservative treatment. Spine surgeries
      for the patients with lumbar spinal stenosis have markedly increased as its
      increasing need, and these surgeries have been believed to improve the quality of
      life. The purpose of this review is to present current information on the spine
      surgery for elderly patients with lumbar spinal stenosis.

PMID- 22460518
TI  - [Locomotive syndrome and frailty. Total knee arthroplasty supports active life of
      the elderly].
AB  - For a society with an aging population, it is important to extend healthy life
      expectancy. Knee arthroplasty is one of the most successful and beneficial
      treatments for osteoarthritic knees, helping the elderly improve their activities
      of daily life. Previous reports have proved health-related quality of life
      improves dramatically with this surgery. In particular, pain and physical
      functioning scores improve significantly. Although the preoperative physical
      activity of each patient does affect the postoperative activity level, sufficient
      improvements can be expected for this procedure on the elderly. These effective
      improvements make the number of knee arthroplasties increase year to year. The
      elderly have high risks of postoperative medical complications. However, long
      term results are comparable or superior to those in younger patients. In elderly
      patients, pre-existing conditions should be carefully controlled, and
      postoperative complications, including infection and thrombosis, should be
      treated prophylactically to promote safety and postoperative recovery.

PMID- 22460519
TI  - Application of Petersen Index score for Dukes'B colorectal cancer in a population
      of 103 consecutive resected patients.
AB  - Dukes' B colorectal cancer (CRC) represents a wide spectrum of disease from early
      penetration through the bowel wall to aggressive and extensive tumours with
      extramural venous spread and involvement of the serosa, surgical margins or
      adjacent organs. Among Dukes' B cancers, Petersen Index allows stratification to
      identify those patients whom chemotherapy may benefit. One hundred and three
      resected patients with CRC Dukes' B were included prospectively in a database and
      considered in the present study. According to Petersen Index, a score (from 0 to
      4) for each patient was calculated on the basis of peritoneal and margin
      involvement, venous invasion and tumour perforation. Twenty-four out of 103
      tumours were located in the rectum and 79 in the colon. According to PI score 59
      patients had a score of 0, 30 of 1 and 14 of >=2. The overall R0 resection was
      achieved in 95.1 % of cases and the majority of patients with PI score of >=2
      were R1-2. The mean of harvested lymph nodes was 23.6 (+/-10.7) with no
      difference according to the PI score. Patients in the high-risk group had a worse
      5-year survival rate (66.3 %) compared with the other group (P < 0.009).
      Multivariate analysis validated the PI score as a significant independent factor
      (P = 0.017). Both high-quality pathology and adequate harvested lymph nodes are
      needed for a proper staging. Even though the influence of PI score on survival is
      confirmed as it leads to an additional rate of colorectal cancer being considered
      for adjuvant therapy, we underline that a comparison with additional clinical and
      histological prognostic factors should be needed.

PMID- 22460520
TI  - Microwave-assisted rapid synthesis of luminescent gold nanoclusters for sensing
      Hg2+ in living cells using fluorescence imaging.
AB  - A microwave-assisted strategy for synthesizing dihydrolipoic acid (DHLA) capped
      fluorescent gold nanoclusters (AuNCs) has been developed. Irradiation with
      microwaves during synthesis enhanced the fluorescence quantum yield (QY) of AuNCs
      by about five-fold and shortened the reaction time from hours to several minutes.
      The as-synthesized DHLA-AuNCs possessed bright near-infrared fluorescence (QY:
      2.9%), ultrasmall hydrodynamic diameter (3.3 nm), good colloidal stability over
      the physiologically relevant pH range of 5-10 as well as low cytotoxicity toward
      HeLa cells. Moreover, these DHLA-AuNCs were capable of sensing Hg(2+) through the
      specific interaction between Hg(2+) and Au(+) on the surface of AuNCs; the limit
      of detection (LOD) was 0.5 nM. A potential application in imaging intracellular
      Hg(2+) in HeLa cells was demonstrated by using spinning disc confocal microscopy.

PMID- 22460521
TI  - Interaction of wild type, G68R and L125M isoforms of the arylamine-N
      acetyltransferase from Mycobacterium tuberculosis with isoniazid: a computational
      study on a new possible mechanism of resistance.
AB  - Isoniazid (INH) is a front-line drug used in the treatment of tuberculosis (TB),
      a disease that remains a major cause of death worldwide. Isoniazid is a prodrug,
      requiring activation in the mycobacterial cell by the catalase-peroxidase (CP)
      enzyme. Recent studies have suggested that acetylation of INH by the arylamine-N
      acetyltransferase from Mycobacterium tuberculosis (TBNAT) may be a possible cause
      of inactivation of the drug thus resulting in resistant strains. In this study,
      computational techniques were applied to investigate the binding of isoniazid to
      three TBNAT isoforms: wild type, G68R and L125M. Since there is no experimental
      structure available, molecular dynamics (MD) simulations were initially used for
      the refinement of TBNAT homology models. Distinct conformations of the models
      were selected during the production stage of MD simulations for molecular docking
      experiments with the drug. Finally, each mode of binding was refined by new
      molecular MD simulations. Essential dynamics (ED) analysis and linear interaction
      energy calculations (LIE) were used to evaluate the impact of amino acid
      substitutions on the structural and binding properties of the enzymes. The
      results suggest that the wild type and the G68R TBNATs have a similar pattern of
      affinity to INH. On the other hand, the calculated enzyme-INH dissociation
      constant (KD) was estimated 33 times lower for L125M isoform in comparison with
      wild type enzyme. This last finding is consistent with the hypothesis that
      isolated mutations in the tbnat gene can produce M. tuberculosis strains
      resistant to isoniazid.

PMID- 22460522
TI  - Identification of diverse dipeptidyl peptidase IV inhibitors via structure-based
      virtual screening.
AB  - Dipeptidyl peptidase IV (DPP4) is an important target for the treatment of type
      II diabetes mellitus. Inhibition of DPP4 will improve glycemic control in such
      patients by preventing the rapid breakdown and thereby prolonging the
      physiological actions of incretin hormones. Known DPP4 inhibitors (including
      marketed drugs and those drug candidates) appear to share similar structural
      features: the cyanopyrrolidine moieties, the xanthenes/pyrimidine parts and amino
      like linkages. In this study, a multi-step virtual screening strategy including
      both rigid and flexible docking was employed to search for novel structures with
      DPP4 inhibition. From SPECS database, consisting of over 190,000 commercially
      available compounds, 99 virtual hits were picked up and 15 of them were
      eventually identified to have DPP4 inhibitory activities at 5 ~ 50 MUM. Diverse
      structures of our compounds were out of usual structural categories. Hence a
      pharmacophore model was built to further explore their common binding features on
      the enzyme. The results provided a new pathway for the discovery of DPP4
      inhibitors and would be helpful for further optimization of DPP4 inhibitors.

PMID- 22460523
TI  - "Russian doll" complexes of [n]cycloparaphenylenes: a theoretical study.
AB  - The formation of "Russian doll" complexes consisting of [n]cycloparaphenylenes
      was predicted using quantum chemistry tools. The electronic structures of
      multiple inclusion complexes containing up to four macrocycles were explored at
      the M06-2X/6-31G* level of theory. The binding energy between the macrocycles
      increases from the center to the periphery of the complex and can be >60 kcal
      mol(-1) for macrocycles containing 14 and 19 repeating units. It has been
      demonstrated that additional electrostatic interactions originating from the
      asymmetric electron density distribution observed when comparing the concave and
      convex macrocycle sides are responsible for the high binding energies in these
      Russian doll complexes. Oxidation or reduction of the Russian doll complexes
      creates polarons that are delocalized across the complexes. In the case of
      polaron cations, most of the polarons are localized at the macrocycle with the
      smallest ionization potential; for polaron anions, the negative charge is
      localized across the outer rings of the complex. Because anion polarons are more
      delocalized than cation polarons, the relaxation energies of the polaron anions
      were found to be smaller than those of the polaron cations.

PMID- 22460524
TI  - A bipyridyl thorium metallocene: synthesis, structure and reactivity.
AB  - The synthesis, structure and reactivity of a new bipy thorium metallocene have
      been studied. The reduction of the thorium chloride metallocene [eta(5)-1,3
      (Me(3)C)(2)C(5)H(3)](2)ThCl(2) (1) with potassium graphite in the presence of
      2,2'-bipyridine gives the purple bipy metallocene [eta(5)-1,3
      (Me(3)C)(2)C(5)H(3)](2)Th(bipy) (2) in good yield. Complex 2 has been fully
      characterized by various spectroscopic techniques, elemental analysis and X-ray
      diffraction analysis. Complex 2 reacts cleanly with trityl chloride, silver
      halides and diphenyl diselenide, leading to the halide metallocenes [eta(5)-1,3
      (Me(3)C)(2)C(5)H(3)](2)ThX(2) (X = Cl (1), Br (3), I (4)) and [eta(5)-1,3
      (Me(3)C)(2)C(5)H(3)](2)Th(F)(MU-F)(3)Th[eta(5)-1,3-(Me(3)C)(2)C(5)H(3)](F)(bipy)
      (5), and selenido metallocene [eta(5)-1,3-(Me(3)C)(2)C(5)H(3)](2)Th(SePh)(2) (6),
      in good conversions. In addition, 2 cleaves the C[double bond, length as m-dash]S
      bond of CS(2) to give the sulfido complex, [eta(5)-1,3-(Me(3)C)(2)C(5)H(3)](2)ThS
      (7), which further undergoes an irreversible dimerization or nucleophilic
      addition with CS(2), leading to the dimeric sulfido complex {[eta(5)-1,3
      (Me(3)C)(2)C(5)H(3)](2)Th}(MU-S)(2) (8) and dimeric trithiocarbonate complex
      {[eta(5)-1,3-(Me(3)C)(2)C(5)H(3)](2)Th}(MU-CS(3))(2) (10) in good yields,
      respectively.

PMID- 22460525
TI  - Posttransplant sinus surgery in lung transplant recipients with cystic fibrosis:
      a single institutional experience.
AB  - Chronic rhinosinusitis is hypothesised to play a major role in lung transplant
      recipients with cystic fibrosis. Paranasal sinuses are considered to accumulate a
      significant bacterial load, potentially leading to lung allograft infection with
      ensuing complications such as bronchiolitis obliterans syndrome, i.e. allograft
      rejection. We therefore would like to present our combined medical and surgical
      treatment plan, which consists of an endoscopic fronto-spheno-ethmoidectomy as
      well as a meticulous daily nasal care program. The microbiological results show
      that our combined concept is effective, whereas especially daily nasal care with
      isotonic saline solution is the cornerstone in preventing significant
      colonisation of the sinuses and spreading bacteria to the lower respiratory tract
      causing lung allograft infection. Regarding the surgical part of our treatment,
      it should be emphasised that all sinuses and ethmoidal air cells should be widely
      opened. Edges such as bony overhangs should be smoothened to avoid mucus
      retention and consecutive bacterial recolonisation requiring subsequent revision
      surgery.

PMID- 22460526
TI  - A minimally invasive approach for cochlear implantation using a microendoscope.
AB  - Given the growing need for minimally invasive approaches to cochlear implantation
      surgery, we chose to examine the safety of a microendoscopic procedure for
      cochlear implantation. We performed cochlear implantation surgery on four human
      temporal bones using a microendoscope and evaluated the safety of the procedure.
      With a microendoscope, the facial recess was opened and electrodes were inserted
      into the cochlea. The size of the mastoidectomy ranged from 5 * 4 to 7 * 7 mm.
      For three of the temporal bones, the surgery was conducted without any damage to
      the surrounding structures. The chorda tympanic nerve was inadvertently
      sacrificed in one temporal bone, in which we skipped the identification of the
      incus. The microendoscope allowed cochlear implantation surgery to be performed
      with a mastoidectomy of minimal size.

PMID- 22460527
TI  - CT-scan prediction of thyroid cartilage invasion for early laryngeal squamous
      cell carcinoma.
AB  - Treatment choice for laryngeal cancer may be influenced by the diagnosis of
      thyroid cartilage invasion on preoperative computed tomography (CT). Our
      objective was to determine the predictive value of CT for thyroid cartilage
      invasion in early- to mid-stage laryngeal cancer. Retrospective study (1992-2008)
      of laryngeal squamous cell carcinoma treated with open partial laryngectomy and
      resection of at least part of the thyroid cartilage. Previous laser surgery,
      radiation therapy, chemotherapy and second primaries were excluded. CT prediction
      of thyroid cartilage invasion was determined by specialized radiologists. Tumor
      characteristics and pathologic thyroid cartilage invasion were compared to the
      radiologic assessment. 236 patients were treated by vertical (20 %), supracricoid
      (67 %) or supraglottic partial laryngectomy (13 %) for tumors staged cT1 (26 %),
      cT2 (55 %), and cT3 (19 %). The thyroid cartilage was invaded on pathology in 19
      cases (8 %). CT's sensitivity was 10.5 %, specificity 94 %, positive predictive
      value 13 %, and negative predictive value 92 %. CT correctly predicted thyroid
      cartilage invasion in only two cases for an overall accuracy of 87 %. Among the
      false-positive CT's, tumors involving the anterior commissure were significantly
      over-represented (61.5 % vs. 27 %, p = .004). Tumors with decreased vocal fold
      (VF) mobility were significantly over-represented in the group of false-negatives
      (41 vs. 13 %, p = .0035). Preoperative CT was not effective in predicting thyroid
      cartilage invasion in these early- to mid-stage lesions, overestimating cartilage
      invasion for AC lesions and underestimating invasion for lesions with decreased
      VF mobility.

PMID- 22460528
TI  - Low MHC class II diversity in the Tasmanian devil (Sarcophilus harrisii).
AB  - The largest remaining carnivorous marsupial, the Tasmanian devil (Sarcophilus
      harrisii), is currently under threat of extinction due to a fatal contagious
      cancer-devil facial tumour disease. Low major histocompatibility complex (MHC)
      class I diversity is believed to have contributed to the transmission of the
      tumour allograft through devil populations. Here, we report low MHC class II
      variability in this species, with DA beta chain genes (Saha-DAB1, 2 and 3)
      exhibiting very limited diversity and the sole alpha chain gene (Saha-DAA)
      monomorphic. Three, six and three alleles were found at Saha-DAB1, 2 and 3,
      respectively, with a predominant allele found at each locus. Heterozygosity at
      these three loci is low in the eastern population and modestly higher in
      northwestern individuals. The results are indicative of a selective sweep likely
      due to an infectious disease resulting in the fixation of selectively favoured
      alleles and depletion of genetic diversity at devil class II loci. Several
      attempts were made to isolate the other marsupial classical class II gene family,
      namely, DB, resulting in only one DBB pseudogene being found. These findings
      further support the view that this species has a compromised capacity to respond
      to pathogen evolution, emerging infectious diseases and environmental changes.

PMID- 22460529
TI  - Reversal of antithrombotic agents.
AB  - Anticoagulants are the mainstay of therapy for thromboembolic diseases. In
      addition to the more traditional agents, new oral anticoagulants, including
      dabigatran etexilate, rivaroxaban, and apixaban, have been shown to be effective
      across several indications. Bleeding is a serious complication associated with
      any anticoagulant, but many of the traditional parenteral and new oral agents do
      not currently have specific antidotes. This review describes available and future
      options for the reversal of the effects of anticoagulants, in particular the new
      oral agents and discusses current management strategies for bleeding events in
      clinical practice.

PMID- 22460530
TI  - Synthesis of Cd(2+)-functionalized titanium phosphate nanoparticles and
      application as labels for electrochemical immunoassays.
AB  - Porous titanium phosphate (TiP) nanoparticles with high water solubility have
      been synthesized by using the surfactant sodium dodecyl sulfate (SDS) as the
      structure-directing agent. The TiP nanoparticles can be functionalized with
      Cd(2+) and can be further used as labels for electrochemical detection of
      proteins due to their excellent ion-exchange property.

PMID- 22460531
TI  - Does AKI truly lead to CKD?
AB  - Acute kidney injury (AKI) has been implicated as an independent risk factor for
      the development of CKD in recent observational studies. The presumption in the
      nephrology community is that this association represents a causal relationship.
      However, because of potential problems related to residual confounding (shared
      risk factors), ascertainment bias (sicker patients have more follow-up
      assessments), misclassification of exposure (problems with defining baseline
      kidney function and AKI representing a discrete event versus progression of renal
      disease), and misclassification of outcome (de novo CKD versus CKD progression),
      it is difficult to conclude with certainty that AKI is truly causal for CKD. In
      this review we highlight several of the Hill causality criteria to examine the
      existing evidence and point out the missing elements that preclude defining AKI
      as a cause of CKD in the general population. Only well-designed studies with
      rigorous assessment of kidney function in all participants (AKI and non-AKI)
      before and after the episode or hospitalization or randomized, controlled trials
      demonstrating that prevention or treatment of AKI reduces the incidence of
      subsequent CKD can clarify the causal nature of the AKI-CKD relationship.

PMID- 22460533
TI  - [Not Available].

PMID- 22460532
TI  - Mechanism of thyrotoxic periodic paralysis.
AB  - The pathogenesis of thyrotoxic periodic paralysis has long been thought related
      to increased Na(+)-K(+) ATPase activity stimulated by thyroid hormone and/or
      hyperadrenergic activity and hyperinsulinemia. This mechanism alone, however,
      cannot adequately explain how hypokalemia occurs during acute attacks or the
      associated paradoxical depolarization of the resting membrane potential. Recent
      findings that loss of function mutations of the skeletal muscle-specific inward
      rectifying K(+) (Kir) channel, Kir2.6, associate with thyrotoxic periodic
      paralysis provide new insights into how reduced outward K(+) efflux in skeletal
      muscle, from either channel mutations or inhibition by hormones (adrenalin or
      insulin), can lead to a vicious cycle of hypokalemia and paradoxical
      depolarization, which in turn, inactivates Na(+) channels and causes muscle
      unexcitability and paralysis.

PMID- 22460534
TI  - [Not Available].

PMID- 22460536
TI  - The TARGET project in Tuscany: the first disease management model of a regional
      project for the prevention of hip re-fractures in the elderly.
AB  - BACKGROUND: The official inquiry on osteoporosis in Italy, promoted by the
      Italian Senate in 2002 concluded that proper preventive strategies should be
      adopted at regional level in order to prevent osteoporotic fractures. Tuscany is
      the first Italian region who has promoted an official program (the TARGET
      project) aimed to reduce osteoporotic fractures by ensuring adequate treatment to
      all people aged >=65 years old who experience a hip fragility fracture.
      OBJECTIVE: this paper provides information concerning the implementation of
      TARGET project in Tuscany, assuming that it may represent an useful model for
      similar experiences to be promoted in other Italian Regions and across Europe.
      METHODS: we have examined the model proposed for the regional program, and we
      have particularly analyzed the in-hospital and post-hospitalization path of hip
      fractured patients aged >65 years old in Tuscany after the adoption of TARGET
      project by Tuscany healthcare system and during its ongoing start-up phase.
      RESULTS: orthopaedic surgeons have been gradually involved in the project and are
      increasingly fulfilling all the clinical prescriptions and recommendations
      provided in the project protocol. Different forms of cooperation between
      orthopaedic surgeons and other clinical specialists have been adopted at each
      hospital for the treatment of hip fractured elderly patients. GPs involvement
      needs to be fostered both at regional and local level. CONCLUSIONS: The effort of
      Tuscany region to cope with hip fractures suffered from elderly people must be
      acknowledged as an interesting way of addressing this critical health problem.
      Specific preventive strategies modelled on the Tuscany TARGET project should be
      implemented in other Italian regions.

PMID- 22460535
TI  - Indications on the use of vitamin D and vitamin D metabolites in clinical
      phenotypes.

PMID- 22460537
TI  - Inhibition of fibroblasts reduced head and neck cancer growth by targeting
      fibroblast growth factor receptor.
AB  - OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCC) is a complex
      disease process involving interactions with carcinoma-associated fibroblasts and
      endothelial cells. We further investigated these relationships by suppressing
      stromal cell growth through the inhibition of fibroblast growth factor receptor
      (FGFR). STUDY DESIGN: Preclinical investigation. METHODS: HNSCC cell lines (FADU,
      OSC19, Cal27, SCC1, SCC5, SCC22A), fibroblast (HS27), and endothelial cells
      (human umbilical vascular endothelial cell) were cultured individually or in
      coculture. Proliferation was assessed following treatment with a range of
      physiologic concentrations of FGFR inhibitor PD173074. Mice bearing established
      HNSCC xenografts were treated with PD173074 (12 mg/kg), and tumor histology was
      analyzed for stromal composition, proliferation (Ki67 staining), and apoptosis
      (TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling] staining).
      RESULTS: In vitro, inhibition of FGFR with PD173074 dramatically reduced
      proliferation of fibroblasts and endothelial cells compared to untreated
      controls. However, HNSCC cell proliferation was not affected by inhibition of
      FGFR. When cocultured with fibroblasts, HNSCC cells proliferation increased by
      15% to 80% (P < .01). Furthermore, this fibroblast-enhanced tumor cell growth was
      suppressed by FGFR inhibition. Additionally, treatment of mice bearing HNSCC
      xenografts with PD173074 resulted in significant growth inhibition (P < .001).
      Additionally, those tumors from mice treated with PD173074 had a smaller stromal
      component, decreased proliferation, and increased apoptosis. CONCLUSIONS:
      Targeting the FGFR pathway in head and neck cancer acts through the stromal
      components to decrease HNSCC growth in vivo and in vitro.

PMID- 22460538
TI  - A weight-loss intervention program designed for Mexican-American women: cultural
      adaptations and results.
AB  - This study assessed the feasibility of a culturally-appropriate weight-loss
      intervention targeting obese Spanish-speaking Mexican women. This 12-month weight
      loss program was based on behavioral interventions previously used successfully
      with English-speaking participants. Cultural adaptations included: female
      interventionists, minimal written materials, emphasis on group activities, focus
      on Mexican traditions and beliefs, and skill-building approach to food
      measurement. All sessions were conducted in Spanish. The study had few
      exclusionary criteria, which allowed participation of women with a wide range of
      literacy levels. Recruitment exceeded expectations, with 47 participants
      enrolling in the program. Not counting participants who became pregnant during
      the study, attendance at 6 and 12 months was 62 and 50 % respectively. Mean
      weight loss at 6 and 12 months was 5.3 and 7.2 kg, respectively, with a mean
      reduction in BMI of 4.0 and 5.5 kg/m(2) from baseline to 6 and 12 months,
      respectively. This pilot study shows that it is feasible to develop and implement
      culturally-appropriate behavioral lifestyle interventions for obesity treatment
      in Mexican-American women.

PMID- 22460539
TI  - Meeting the challenge of IBS.
AB  - Irritable bowel syndrome is frustrating and debilitating for patients, and
      management of this disorder is a challenge for healthcare providers. IBS is a
      common, functional, gastrointestinal disorder, and is often characterized by
      crippling symptoms without any pathologic findings.

PMID- 22460540
TI  - Peripheral neuropathy: evidence-based treatment of a complex disorder.
AB  - Peripheral neuropathy (PN) is a common and often progressive condition frequently
      seen in primary care. The chronic pain associated with PN, or neuropathic pain,
      can significantly diminish patients' quality of life and be challenging to treat.

PMID- 22460542
TI  - Second trimester maternal plasma levels of cytokines IL-1Ra, Il-6 and IL-10 and
      preterm birth.
AB  - OBJECTIVE: To examine the interaction of the cytokines interleukin-1 receptor
      antagonist (IL)-1Ra, IL-6 and IL-10 to predict preterm birth (PTB) in pregnant
      Hispanic women (n=470). STUDY DESIGN: In this prospective study, demographic data
      were obtained prenatally and birth outcome data were obtained from the medical
      chart. Cytokines were measured from plasma obtained at 22 to 24 weeks gestation.
      Data analysis utilized logistic regression. RESULT: PTB was predicted by level of
      IL-1Ra (odds ratio (OR)=2.55; 95% confidence interval (CI)=1.24, 5.24). The
      interaction between IL-1Ra and IL-6 and between IL-1Ra and IL-10 was significant
      (Wald=4.01, P=0.04 and Wald=8.84, P<0.003, respectively) and was also predictive
      of PTB. As IL-1Ra levels increased while IL-10 levels were low, the probability
      of PTB greatly increased. CONCLUSION: The interactions of select cytokines and
      cytokine receptor antagonists were associated with PTB. Future research should
      focus on the changes in cytokines during pregnancy to identify critical periods
      of change, and examine predictors of the cytokine response.

PMID- 22460541
TI  - The effect of job strain on nighttime blood pressure dipping among men and women
      with high blood pressure.
AB  - OBJECTIVES: Blunted nighttime blood pressure dipping is an established
      cardiovascular risk factor. This study examined the effect of job strain on
      nighttime blood pressure dipping among men and women with high blood pressure.
      METHODS: The sample consisted of 122 blue- and white collar workers (men=72,
      women=50). The Job Content Questionnaire was used to measure job psychological
      demands, job control, and social support. The ratio of job demands to job control
      was used to assess job strain. Nighttime blood pressure dipping was evaluated
      from 24-hour ambulatory blood pressure monitoring performed on three workdays.
      RESULTS: Men with high job strain had a 5.4 mm Hg higher sleep systolic blood
      pressure (P=0.03) and 3.5 mm Hg higher sleep pulse pressure (P=0.02) compared to
      men with low job strain. Men with high job strain had a smaller fall in systolic
      blood pressure and pulse pressure from awake to sleep state than those with low
      job strain (P<0.05). Hierarchical analyses showed that job strain was an
      independent determinant of systolic blood pressure dipping (P=0.03) among men
      after adjusting for ethnicity, body mass index, anxiety and depression symptoms,
      current smoking status, and alcohol consumption. Further exploratory analyses
      indicated that job control was the salient component of job strain associated
      with blood pressure dipping (P=0.03). CONCLUSIONS: High job strain is associated
      with a blunting of the normal diurnal variation in blood pressure and pulse
      pressure, which may contribute to the relationship between job strain and
      cardiovascular disease.

PMID- 22460543
TI  - Prolonged persistent patent ductus arteriosus: potential perdurable anomalies in
      premature infants.
AB  - OBJECTIVE: Patent ductus arteriosus (PDA) is a common condition among preterm
      infants. Controversy exists regarding the risk-benefit ratio of early closure of
      PDAs by either medical or surgical treatments. On the other hand, potential
      morbidities associated with no or delayed closure has not been well studied. The
      objective of the study was to determine if there is an association of prolonged
      persistent PDA (PP-PDA) with various morbidities in infants <=28 weeks or 1250 g.
      STUDY DESIGN: This matched case-control analysis includes preterm infants with a
      diagnosis of PDA over a period of 28 months in a single level III center in the
      USA. The predictive variable was the presence of a PP-PDA (PDA>3 weeks). Cases
      were infants with PP-PDA and controls were those with PDA but not PP-PDA (two
      controls for each case). Outcome variables included days on mechanical
      ventilation and with oxygen treatment, length of hospital stay, bronchopulmonary
      dysplasia (BPD), retinopathy of prematurity stage III-V (ROP) necrotizing
      enterocolitis grade II or more (NEC), delayed growth, direct hyperbilirubinemia
      >4 mg dl(-1) and osteopenia of prematurity. Data was obtained from database
      collected prospectively and from the review of clinical records when necessary.
      Statistics included ANOVA, Kaplan-Meier curves and chi (2). Significance was set
      at P<0.05. RESULT: PP-PDA was associated with a significant increase in the
      number of days of mechanical ventilation, oxygen treatment and length of hospital
      stay, and in the rates of BPD (60% vs 4.5%), NEC (29% vs 5%), ROP (43% vs 5%),
      direct hyperbilirubinemia (41% vs 3%), osteopenia (44% vs 6%), parenteral
      nutrition for >40 days (70% vs 21%), tracheostomy during the hospitalization (15%
      vs 0%) and delayed growth (70% vs 21%), were also significantly higher in babies
      with PP-PDA. CONCLUSION: A prolonged exposure to PDA does not seem to be
      inconsequential for some infants and is associated with an increase prevalence of
      severe morbidities with potential long lasting effects.

PMID- 22460544
TI  - A delivery room-focused education and deliberate practice can improve pediatric
      resident resuscitation training.
AB  - OBJECTIVE: To determine if deliberate practice and simulation would improve
      pediatric residents' neonatal resuscitation abilities. STUDY DESIGN: Prospective
      cohort with pre-post-intervention design. Senior residents from 2008 to 2009 were
      evaluated and served as controls (C-Senior, N=23). Interns (PL-1, N=28) from 2008
      to 2009 received the education and evaluation at the beginning (I-Pre) and end of
      their NICU rotation (I-Post) and again when they were seniors (I-Senior, N=24).
      The education, based on deliberate practice, included scored assessments of a
      resident's ability to assemble delivery room equipment and lead a simulated
      resuscitation. RESULT: PL-1 equipment score increased by 30% (I-Pre; 53%, I-Post;
      83%) and was not different 1 to 2 years later (I-Senior; 87%). I-Senior equipment
      score was 22% higher than the C-Senior group (C-Senior; 65%). The PL-1's ability
      to lead a resuscitation improved after the education (I-Pre; 76%, I-Post; 85%)
      and was maintained as senior residents (I-Senior; 85%), but was not superior to
      the C-Senior group (C-Senior; 81%). CONCLUSION: The use of deliberate practice
      and simulation can improve a residents' resuscitation training, particularly for
      equipment.

PMID- 22460545
TI  - Pilot study of experiences and needs of 111 fathers of very low birth weight
      infants in a neonatal intensive care unit.
AB  - OBJECTIVE: To study the experiences and needs of the fathers of very low birth
      weight (VLBW, <1500 g) infants in a neonatal intensive care unit (NICU). STUDY
      DESIGN: An anonymous self-report questionnaire was administered to fathers of
      VLBW infants born between Jan 1, 2008 and December 31, 2009 at two tertiary
      NICUs. RESULT: A total of 111 of 273 fathers responded to the questionnaire.
      Responses to a variety of items, including self-perception, parenting attitudes,
      confidence, emotional pressure to satisfaction and self-efficacy as a parent were
      similar for the fathers of this survey and previous results for mothers of VLBW
      infants. Fathers judged direct bedside support by the NICU team as sufficient.
      However, 54.4% of fathers reported missing nonbedside interventions such as VLBW
      father-specific baby care courses, seminars or workshops, and platforms or
      chatrooms on the internet. CONCLUSION: Bedside support of fathers, accomplished
      by the NICU team, could be complemented by additional father-specific non-bedside
      support, such as peer-education measures or interactive mass media.

PMID- 22460546
TI  - Proactive management of extreme prematurity: disagreement between obstetricians
      and neonatologists.
AB  - OBJECTIVE: To verify, in extremely preterm infants, if disagreement between
      obstetricians and neonatologists regarding proactive management is associated
      with early death. STUDY DESIGN: Prospective cohort of 484 infants with 23(0/7) to
      26(6/7) weeks, without malformations, born from January 2006 to December 2009 in
      eight Brazilian hospitals. Pro-active management was defined as indication of >=1
      dose of antenatal steroid or cesarean section (obstetrician) and resuscitation at
      birth according to the international guidelines (neonatologist). Main outcome was
      neonatal death in the first 24  h of life. RESULT: Obstetricians and
      neonatologists disagreed in 115 (24%) patients: only neonatologists were
      proactive in 107 of them. Disagreement between professionals increased 2.39 times
      the chance of death in the first day (95% confidence interval 1.40 to 4.09),
      adjusted for center and maternal/neonatal clinical conditions. CONCLUSION: In
      infants with 23 to 26 weeks of gestation, disagreement between obstetricians and
      neonatologists, translated as lack of antenatal steroids and/or vaginal delivery,
      despite resuscitation procedures, increases the odds of death in the first day.

PMID- 22460547
TI  - Role of perisynaptic parameters in neurotransmitter homeostasis--computational
      study of a general synapse.
AB  - Extracellular neurotransmitter concentrations vary over a wide range depending on
      the type of neurotransmitter and location in the brain. Neurotransmitter
      homeostasis near a synapse is achieved by a balance of several mechanisms
      including vesicular release from the presynapse, diffusion, uptake by
      transporters, nonsynaptic production, and regulation of release by autoreceptors.
      These mechanisms are also affected by the glia surrounding the synapse. However,
      the role of these mechanisms in achieving neurotransmitter homeostasis is not
      well understood. A biophysical modeling framework was proposed, based on a
      cortico-accumbens synapse example case, to reverse engineer glial configurations
      and parameters related to homeostasis for synapses that support a range of
      neurotransmitter gradients. Model experiments reveal that synapses with
      extracellular neurotransmitter concentrations in the micromolar range require
      nonsynaptic neurotransmitter sources and tight synaptic isolation by
      extracellular glial formations. The model was used to identify the role of
      perisynaptic parameters on neurotransmitter homeostasis and to propose glial
      configurations that could support different levels of extracellular
      neurotransmitter concentrations. Ranking the parameters based on their effect on
      neurotransmitter homeostasis, nonsynaptic sources were found to be the most
      important followed by transporter concentration and diffusion coefficient.

PMID- 22460549
TI  - Terrestrial nest-building by wild chimpanzees (Pan troglodytes): implications for
      the tree-to-ground sleep transition in early hominins.
AB  - Nest-building is a great ape universal and arboreal nesting in chimpanzees and
      bonobos suggests that the common ancestor of Pan and Homo also nested in trees.
      It has been proposed that arboreal nest-building remained the prevailing pattern
      until Homo erectus, a fully terrestrial biped, emerged. We investigated the
      unusual occurrence of ground-nesting in chimpanzees (Pan troglodytes), which may
      inform on factors influencing the tree-to-ground sleep transition in the hominin
      lineage. We used a novel genetic approach to examine ground-nesting in
      unhabituated chimpanzees at Seringbara in the Nimba Mountains, Guinea. Previous
      research showed that ground-nesting at Seringbara was not ecologically
      determined. Here, we tested a possible mate-guarding function of ground-nesting
      by analyzing DNA from shed hairs collected from ground nests and tree nests found
      in close proximity. We examined whether or not ground-nesting was a group-level
      behavioral pattern and whether or not it occurred in more than one community. We
      used multiple genetic markers to identify sex and to examine variation in
      mitochondrial DNA control region (HV1, HV2) sequences. Ground-nesting was a male
      biased behavior and males constructed more elaborate ("night") nests than simple
      ("day") nests on the ground. The mate-guarding hypothesis was not supported, as
      ground and associated tree nests were built either by maternally-related males or
      possibly by the same individuals. Ground-nesting was widespread and likely
      habitual in two communities. We suggest that terrestrial nest-building may have
      already occurred in arboreally-adapted early hominins before the emergence of H.
      erectus.

PMID- 22460550
TI  - Pro-inflammatory phospholipid arachidonic acid/eicosapentaenoic acid ratio of
      dysmetabolic severely obese women.
AB  - BACKGROUND: Fatty acids (FAs) and adipokines such as adiponectin or interleukin-6
      (IL-6) are known to modulate inflammation and the development of metabolic
      syndrome. Whether FA composition assessed in plasma triacylglycerols (TAGs),
      phospholipids (PLs) and non-esterified fatty acids (NEFAs) and adipose tissue
      (AT) PLs differed between dysmetabolic and non-dysmetabolic severely obese women
      remains to be established. Whether the plasma and/or AT arachidonic acid
      (AA)/eicosapentaenoic acid (EPA) ratio in the PL sub-fraction may be associated
      with adipokine AT gene expression needs to be examined. METHODS: FA composition
      was measured in plasma lipid classes and in the TAG and PL sub-fractions of
      subcutaneous abdominal and omental ATs of severely obese women paired for age and
      adiposity but showing a dysmetabolic profile (n = 13) or not (n = 14). FA profile
      was assessed by gas chromatography. Plasma and AT mRNA concentrations of
      adiponectin and IL-6 were measured by ELISA and real-time polymerase chain
      reaction, respectively. RESULTS: Plasma adiponectin and FA concentrations in the
      NEFA sub-fraction were, respectively, lower and higher in dysmetabolic than in
      non-dysmetabolic women (p < 0.05). Despite similar FA levels in the PL sub
      fraction, the AA/EPA ratio was higher in plasma and ATs (p < 0.005), because of
      an EPA decrease in plasma and subcutaneous abdominal fat vs. an AA increase in
      the omental depot. The AA/EPA ratio was negatively associated with adiponectin
      concentrations in plasma and subcutaneous abdominal AT (0.01 < p < 0.05).
      CONCLUSIONS: Metabolic dysfunction is associated with a pro-inflammatory
      phospholipid AA/EPA ratio in plasma and ATs, and an altered adiponectin secretion
      that could contribute to developing metabolic syndrome.

PMID- 22460551
TI  - Transgastric endoscopic retrograde cholangiopancreatography for the management of
      biliary tract disease after Roux-en-Y gastric bypass treatment for obesity.
AB  - Roux-en-Y gastric bypass (RYGB) is an effective treatment for morbid obesity.
      However, it may lead to diseases of the bilio-pancreatic tract. We evaluated
      transgastric endoscopic retrograde cholangiopancreatography (ERCP) for managing
      common biliary tract diseases in patients that underwent RYGB treatment for
      obesity. This prospective study was conducted between 2003 and 2010 at three
      medical institutions. We included 23 patients with a mean body mass index of 28.2
      kg/m(2) after RYGB treatment. ERCP was performed in all patients to manage
      biliary tract diseases within 9 to 27 months (mean 16.3 months) of RYGB surgery.
      The gastrotomy was conducted through the anterior wall of the greater curve of
      the excluded stomach. A duodenoscope was introduced in the direction of the
      ostomy to perform the ERCP with sphincterotomy. All patients underwent an ERCP
      and papillotomy without incident. Ten patients underwent simultaneous
      cholecystectomy. A total of 17 gallstones were removed. The average gastrotomy
      duration was 92.69 min; the average hospital stay was 2 days. One patient had
      mild acute pancreatitis that resolved clinically. There was no mortality.
      Laparoscopy-assisted transgastric ERCP was feasible and safe for patients after
      RYGB. The necessary equipment is available in most bariatric surgery centers.

PMID- 22460552
TI  - Change of electrical conductivities between hydrated and dehydrated samples of
      honeycomb sheet structures with mixed oxidation state paddlewheel dirhodium
      complexes and halide ions.
AB  - A series of mixed oxidation state compounds, [{Rh(2)(acam)(4)}(3)(MU(3)
      X)(2)].nH(2)O (Hacam = acetamide; X = Cl, n = 4 (1.4H(2)O); X = Br, n = 10
      (2.10H(2)O); X = I, n = 10 (3.10H(2)O)) and [{Rh(2)(pram)(4)}(3)(MU(3)
      X)(2)].6H(2)O (Hpram = propionamide; X = Cl (4.6H(2)O), Br (5.6H(2)O), I
      (6.6H(2)O)) were synthesized and their X-ray structures were determined. In the
      crystal structure of all of these complexes, dirhodium complexes and halide ions
      construct 2-D honeycomb sheet arrangements in which the walls consist of Rh(2)
      units and halide ions lie at the corners. Complexes 1.4H(2)O, 4.6H(2)O, 5.6H(2)O
      and 6.6H(2)O have three independent Rh(2) units, in which there are two Rh(2)(5+)
      and one Rh(2)(4+). In these structures, the water molecules hydrogen bond to O
      atoms and from the N atoms of the amidate ligands. The number of hydrogen bonds
      from water molecules to the Rh(2)(4+) unit is greater than that to the Rh(2)(5+)
      units. This suggests that there exists pinning of the oxidation states by water
      molecules. In the structures of 2.10H(2)O and 3.10H(2)O, all of the Rh(2) units
      are crystallographically equivalent. In these structures, eight of the 10 water
      molecules form a honeycomb-like network between the {Rh(2)(acam)(4)}(3)X(2)
      honeycomb sheets. The former four structures show very low electrical
      conductivities of ca. 10(-8) S cm(-1) (room temperature, pellets) and the latter
      structures have the higher values of ca. 10(-4) S cm(-1). In the former
      complexes, improvement of the values to 10(-6) S cm(-1) was observed, caused by
      loss of pinning water.

PMID- 22460553
TI  - Formation of polycyclic aromatic hydrocarbons from acetylene over nanosized
      olivine-type silicates.
AB  - The formation mechanism of polycyclic aromatic hydrocarbon (PAH) molecules in
      interstellar and circumstellar environments is not well understood although the
      presence of these molecules is widely accepted. In this paper, addition and
      aromatization reactions of acetylene over astrophysically relevant nesosilicate
      particles are reported. Gas-phase PAHs produced from exposure of acetylene gas to
      crystalline silicates using pulsed supersonic jet expansion (SJE) conditions were
      detected by time-of-flight mass spectrometry (TOF-MS). The PAHs produced were
      further confirmed in a separate experiment using a continuous flow fixed-bed
      reactor in which acetylene was introduced at atmospheric pressure. The gas-phase
      effluent and solutions of the carbonaceous compounds deposited on the
      nesosilicate particles were analyzed using gas chromatography-mass spectrometry
      (GC-MS). A mechanism for PAH formation is proposed in which the Mg(2+) ions in
      the nesosilicate particles act as Lewis acid sites for the acetylene reactions.
      Our studies indicate that the formation of PAHs in mixed-chemistry astrophysical
      environments could arise from acetylene interacting with olivine nano-particles.
      These nesosilicate particles are capable of providing catalytic centres for
      adsorption and activation of acetylene molecules that are present in the
      circumstellar environments of mass-losing carbon stars. The structure and
      physical properties of the particles were characterized by means of X-ray
      diffraction (XRD), Fourier transform infrared (FT-IR) and high-resolution
      transmission electron microscopy (HRTEM) techniques.

PMID- 22460554
TI  - Deletion of the angiotensin II type 1a receptor prevents atherosclerotic plaque
      rupture in apolipoprotein E-/- mice.
AB  - OBJECTIVE: Angiotensin II is involved in the genesis of atherosclerosis. As the
      role of the angiotensin II type 1a (AT(1a)) receptor in plaque rupture is poorly
      understood, we assessed the hypothesis that the AT(1a)receptor contributes to
      atherosclerotic plaque rupture. METHODS AND RESULTS: Atherosclerotic plaque
      rupture was induced by carotid artery ligation for 4 weeks followed by
      polyethylene cuff placement around the carotid in apolipoprotein E (ApoE)(-/-)
      and ApoE(-/-) AT(1a)(-/-) mice. The incidence of plaque rupture at 4 days after
      cuff placement was 72% in ApoE(-/-) mice compared with 24% in ApoE(-/-) AT(1a)(-/
      ) mice (P<0.01). Lipid accumulation, macrophage infiltration, expression of
      inflammatory cytokines, nicotinamide adenine dinucleotide phosphate-oxidase
      activity, and matrix metalloproteinase-9 activity in atherosclerotic plaque were
      markedly attenuated in ApoE(-/-) AT(1a)(-/-) compared with ApoE(-/-) mice.
      Oxidized low-density lipoprotein inhibited macrophage migration in ApoE(-/-)
      macrophages. In contrast, oxidized low-density lipoprotein-induced macrophage
      trapping was abolished in ApoE(-/-) AT(1a)(-/-) macrophages, and this was
      associated with decreased CD36 expression and focal adhesion kinase activity.
      CONCLUSIONS: Conclusion- These results suggest that blocking the AT(1) receptor
      may reduce atherosclerotic plaque rupture and that AT(1a) receptor-mediated
      macrophage trapping, inflammation, oxidative stress, and matrix metalloproteinase
      activation may play crucial roles in plaque vulnerability.

PMID- 22460555
TI  - Angiotensin converting enzyme 2 contributes to sex differences in the development
      of obesity hypertension in C57BL/6 mice.
AB  - OBJECTIVE: Obesity promotes hypertension, but it is unclear if sex differences
      exist in obesity-related hypertension. Angiotensin converting enzyme 2 (ACE2)
      converts angiotensin II (AngII) to angiotensin-(1-7) (Ang-[1-7]), controlling
      peptide balance. We hypothesized that tissue-specific regulation of ACE2 by high
      fat (HF) feeding and sex hormones contributes to sex differences in obesity
      hypertension. METHODS AND RESULTS: HF-fed females gained more body weight and fat
      mass than males. HF-fed males exhibiting reduced kidney ACE2 activity had
      increased plasma angiotensin II levels and decreased plasma Ang-(1-7) levels. In
      contrast, HF-fed females exhibiting elevated adipose ACE2 activity had increased
      plasma Ang-(1-7) levels. HF-fed males had elevated systolic and diastolic blood
      pressure that were abolished by losartan. In contrast, HF-fed females did not
      exhibit increased systolic blood pressure until females were administered the Ang
      (1-7) receptor antagonist, D-Ala-Ang-(1-7). Deficiency of ACE2 increased systolic
      blood pressure in HF-fed males and females, which was abolished by losartan.
      Ovariectomy of HF-fed female mice reduced adipose ACE2 activity and plasma Ang-(1
      7) levels, and promoted obesity-hypertension. Finally, estrogen, but not other
      sex hormones, increased adipocyte ACE2 mRNA abundance. CONCLUSIONS: These results
      demonstrate that tissue-specific regulation of ACE2 by diet and sex hormones
      contributes to sex differences in obesity-hypertension.

PMID- 22460556
TI  - Common and low-frequency genetic variants in the PCSK9 locus influence
      circulating PCSK9 levels.
AB  - OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating
      protein that influences plasma low-density lipoprotein concentration and
      susceptibility to coronary heart disease. Circulating PCSK9 levels show
      considerable interindividual differences, but the factors responsible for this
      variation are largely unknown. METHODS AND RESULTS: We analyzed circulating PCSK9
      levels in 4 cohorts of healthy, middle-aged Swedes (n=5722) and found that PCSK9
      levels varied over ~50-fold range, showed a positive relationship with plasma low
      density lipoprotein-cholesterol concentration, and were associated with plasma
      triglyceride, fibrinogen, insulin, and glucose concentrations. A genome-wide
      association study conducted in 2 cohorts (n=1215) failed to uncover common
      genetic variants robustly associated with variation in circulating PCSK9 level.
      As expected, the minor allele of the PCSK9 R46L variant was in all cohorts
      associated with reduced PCSK9 levels and decreased plasma low-density lipoprotein
      cholesterol concentrations, but no relationship was observed with the plasma
      triglyceride concentration. Further mapping of the PCSK9 locus revealed a common
      polymorphism (rs2479415, minor allele frequency 43.9%), located ~6 kb upstream
      from PCSK9, which is independently associated with increased circulating PCSK9
      levels. CONCLUSIONS: Common and low-frequency genetic variants in the PCSK9 locus
      influence the pronounced interindividual variation in circulating PCSK9 levels in
      healthy, middle-aged white (predominantly Swedish) subjects.

PMID- 22460558
TI  - Potential role of upstream stimulatory factor 1 gene variant in familial combined
      hyperlipidemia and related disorders.
AB  - OBJECTIVE: Genetic studies implicated upstream stimulatory factor 1 (USF1) in
      familial combined hyperlipidemia because the rs2073658 minor allele was
      associated with reduced risk of familial combined hyperlipidemia and related
      disorders. The molecular mechanisms whereby rs2073658 influences trait expression
      have remained elusive. METHODS AND RESULTS: Plasma lipids, rs2073658 genotypes
      (N=372), and hepatic transcript levels (N=96) of USF1 and genes involved in
      hepatic lipoprotein production were determined in obese subjects. The rs2073658
      minor allele was associated with reduced plasma triglycerides (TGs) (P<0.001),
      hepatic USF1 (P<0.01), and microsomal TG transfer protein transcript levels
      (P<0.05). Functional studies in human hepatocellular carcinoma cells showed that
      rs2073658 is located in a forkhead box A2 (FOXA2) binding site and that major
      allele constructs displayed higher transcriptional activity than minor allele
      constructs. Knockdown of FOXA2 reduced the activity of major, but not minor
      allele constructs. Furthermore, an interaction between hepatic FOXA2 transcript
      levels and rs2073658 minor allele carrier status on hepatic USF1 transcript
      levels was observed in vivo (P<0.05). USF1 activated the transcription of FOXA2
      and FOXA2 strongly activated the transcription of microsomal TG transfer protein.
      CONCLUSIONS: A feed-forward loop comprising activation of USF1 transcription by
      FOXA2 and activation of FOXA2 transcription by USF1, driving microsomal TG
      transfer protein expression, is modulated by rs2073658. Hence, rs2073658 likely
      influences hepatic TG secretion.

PMID- 22460559
TI  - Divergent effects of p47(phox) phosphorylation at S303-4 or S379 on tumor
      necrosis factor-alpha signaling via TRAF4 and MAPK in endothelial cells.
AB  - OBJECTIVE: To define the mechanism of p47(phox) phosphorylation in regulating
      endothelial cell response to tumor necrosis factor-alpha (TNFalpha) stimulation.
      METHODS AND RESULTS: We replaced 11 serines (303-4, 310, 315, 320, 328, 345, 348,
      359, 370, and 379) with alanines and investigated their effects on TNFalpha (100
      U/mL, 30 minutes)-induced acute O(2)(.-) production and mitogen-activated protein
      kinase phosphorylation in endothelial cells. Seven constructs, S303-4A (double),
      S310A, S315A, S328A, S345A, S370A, and S379A, significantly reduced the O(2)(.-)
      production, and 4 of them (S328A, S345A, S370A, and S379A) also inhibited
      TNFalpha-induced extracellular-signal-regulated kinase (ERK) 1/2 phosphorylation.
      Blocking the phosphorylation of S303-4 and S379 inhibited most effectively
      TNFalpha-induced O(2)(.-) production. However, phosphorylation of S303-4 was not
      required for TNFalpha-induced p47(phox) membrane translocation and binding to TNF
      receptor-associated factor 4, ERK1/2 activation, and subsequent vascular cell
      adhesion molecule-1 expression. Knockout of p47(phox) or knockdown of TNF
      receptor-associated factor 4 using siRNA abolished TNFalpha-induced ERK1/2
      phosphorylation, and inhibition of ERK1/2 activation significantly reduced the
      TNFalpha-induced vascular cell adhesion molecule-1 expression. CONCLUSIONS:
      Phosphorylation of p47(phox) at different serine sites plays distinct roles in
      endothelial cell response to TNFalpha stimulation. Double serine (S303-4)
      phosphorylation is crucial for acute O(2)(.-) production, but is not involved in
      TNFalpha signaling through TNF receptor-associated factor 4 and ERK1/2. p47(phox)
      requires serine phosphorylation at distinct sites to support specific signaling
      events in response to TNFalpha.

PMID- 22460557
TI  - Endogenous nitric oxide synthase inhibitors in the biology of disease: markers,
      mediators, and regulators?
AB  - The asymmetric methylarginines inhibit nitric oxide synthesis in vivo by
      competing with L-arginine at the active site of nitric oxide synthase. High
      circulating levels of asymmetric dimethylarginine predict adverse outcomes,
      specifically vascular events but there is now increasing experimental and
      epidemiological evidence that these molecules, and the enzymes that regulate this
      pathway, play a mechanistic role in cardiovascular diseases. Recent data have
      provided insight into the impact of altered levels of these amino acids in both
      humans and rodents, however these reports also suggest a simplistic approach
      based on measuring, and modulating circulating asymmetric dimethylarginine alone
      is inadequate. This review outlines the basic biochemistry and physiology of
      endogenous methylarginines, examines both the experimental and observational
      evidence for a role in disease pathogenesis, and examines the potential for
      therapeutic regulation of these molecules.

PMID- 22460560
TI  - The majority of genetic variation in orangutan personality and subjective well
      being is nonadditive.
AB  - The heritability of human personality is well-established. Recent research
      indicates that nonadditive genetic effects, such as dominance and epistasis, play
      a large role in personality variation. One possible explanation for the latter
      finding is that there has been recent selection on human personality. To test
      this possibility, we estimated additive and nonadditive genetic variance in
      personality and subjective well-being of zoo-housed orangutans. More than half of
      the genetic variance in these traits could be attributed to nonadditive genetic
      effects, modeled as dominance. Subjective well-being had genetic overlap with
      personality, though less so than has been found in humans or chimpanzees. Since a
      large portion of nonadditive genetic variance in personality is not unique to
      humans, the nonadditivity of human personality is not sufficient evidence for
      recent selection of personality in humans. Nonadditive genetic variance may be a
      general feature of the genetic structure of personality in primates and other
      animals.

PMID- 22460561
TI  - Animal models of neurological disorders.

PMID- 22460563
TI  - Abstracts of the 6th cachexia conference, milan, Italy, december 8-10, 2011 (part
      2).

PMID- 22460562
TI  - Delivery of large molecules via poly(butyl cyanoacrylate) nanoparticles into the
      injured rat brain.
AB  - Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles have been successfully applied
      to deliver small-molecule drugs to the central nervous system (CNS). However, it
      is unclear whether PBCA nanoparticles can be used as the delivery system for
      large molecules to potentially treat traumatic brain injury (TBI). In this study,
      we tested the capacity of PBCA nanoparticles in passing through the blood-brain
      barrier (BBB) and transporting large molecules into normal and injured brains in
      the rat. We first synthesized PBCA nanoparticles by dispersion polymerization and
      then loaded the particles with either horseradish peroxidase (HRP, 44 kDa) or
      enhanced green fluorescent protein (EGFP, 29 kDa), which were further coated with
      polysorbate 80. Next, the polysorbate 80-coated HRP or EGFP-loaded PBCA
      nanoparticles were intravenously injected into the normal and brain-injured rats.
      We found that, at 45 min after injection, PBCA nanoparticle-delivered HRP or EGFP
      was hardly detected in the normal brains of the rats, but a small amount of EGFP
      carried by PBCA nanoparticles was noted in the normal brains 48 h after
      administration, which was further confirmed by immunolocalization with anti-EGFP
      antibodies. In contrast, at 4 h after TBI with a circulation time of 45 min,
      although the penetration of HRP or EGFP alone was hampered by the BBB, the PBCA
      nanoparticle-delivered HRP or EGFP was widely distributed near injured sites.
      Together, our findings provide histological evidence that PBCA nanoparticles can
      be used as an efficient delivery system for large molecules to overcome the
      barrier in the brain with TBI.

PMID- 22460564
TI  - Inhibitory effects of free ammonia on Anammox bacteria.
AB  - Anammox bacteria can effectively treat high ammonia and nitrite concentrations
      under anoxic environments. However, the presence of high ammonia and nitrite
      concentrations may cause free ammonia and nitrous acid inhibition at high pH and
      temperature environments. In this study, the inhibitory effect of free ammonia on
      Anammox bacteria was investigated in a lab-scale upflow fixed-bed reactor with
      Kaldnes biofilm carriers. Results of continuous operation showed that inhibition
      was not observed in the Anammox reactor when the free ammonia concentration
      gradually increased up to 150 mg/L. However, Anammox activity suddenly dropped to
      10 % when the free ammonia concentration reached to 190 mg/L. Nevertheless, high
      influent ammonia and nitrite concentrations up to 1,500 and 500 mg/L,
      respectively, did not noticeably inhibit the Anammox activity. Gradually
      decreasing Anammox activity was also supported by fluorescent in situ
      hybridization (FISH) analysis. FISH and 16S rRNA gene analysis results revealed
      that main Anammox organisms were phylogenetically related to Candidatus Kuenenia
      stuttgartiensis, Candidatus Jettenia asiatica and Candidatus Brocadia
      anammoxidans.

PMID- 22460565
TI  - A physician order category-based clinical guideline comparison system.
AB  - Today, in order to provide high-quality medical services and to extend resources
      and reduce costs, many large hospitals have adopted clinical guidelines as a
      structured way to manage medical activities. However, customization of clinical
      guidelines in order to treat a large number of patients is a major challenge. In
      this paper, we present a physician order category-based clinical guideline
      comparison system. The system uses a preprocessor software to convert the
      clinical guidelines from a Microsoft Word document into XML format, and it can
      also compare clinical guidelines over the conceptual view such as the physician
      order category. The system has already been used to compare the HCC surgical
      clinical guidelines of Taiwan and Mongolia-resulting in some differences being
      found, for which possible causes were discussed. Therefore, it can be seen that
      our research provides a practical and convenient way in which to compare clinical
      guidelines based on physician order category-thereby saving time and enabling
      physicians to quickly resolve discrepancies and make necessary adjustments to
      clinical guidelines.

PMID- 22460567
TI  - Technical note: Bone DNA extraction and purification using silica-coated
      paramagnetic beads.
AB  - The goal of this study was to develop a simple method to improve DNA recovery
      from challenging bone samples. To this end, an optimized procedure was developed
      that combined the demineralization and DNA extraction into a single step,
      followed by DNA purification using an automated silica-coated paramagnetic bead
      procedure. This method replaced a previous silica-membrane-based procedure, which
      was able to recover sufficient DNA to obtain full autosomal and Y chromosome STR
      profiles from greater than 90% of the samples, including samples greater than 20
      years old. The development process began with the evaluation of buffer and
      demineralization systems to determine the best reagent combination. During the
      developmental process, we observed that the addition of EDTA and DTT affected
      silica-based DNA purification methods by raising the pH of the digest buffer. The
      protocols with buffer ATL, PK, EDTA, and DTT followed by lowering the pH with
      sodium acetate just before purification resulted in the best yields. The method
      reduced the extraction volume from 10 to 1.5 ml and used commercially available
      reagents already being utilized in forensic DNA casework. Because of the
      simplicity and small volume needed for the procedure, many steps where
      contamination could be introduced have been eliminated or minimized. This study
      demonstrated a new method of recovering DNA from bone samples capable of
      extracting trace quantities of DNA, removing potential inhibitors, and minimizing
      the potential for exogenous DNA contamination.

PMID- 22460568
TI  - [Transient lower esophageal sphincter relaxation and the related esophageal motor
      activities].
AB  - Transient lower esophageal sphincter (LES) relaxation (TLESR) is defined as LES
      relaxation without a swallow. TLESRs are observed in both of the normal
      individuals and the patients with gastroesophageal reflux disorder (GERD).
      However, TLESR is widely considered as the major mechanism of the GERD. The new
      equipments such as high resolution manometry and impedance pH study is helped to
      understand of TLESR and the related esophageal motor activities. The strong
      longitudinal muscle contraction was observed during development of TLESR. Most of
      TLESRs are terminated by TLESR related motor events such as primary peristalsis
      and secondary contractions. The majority of TLESRs are associated with
      gastroesophageal reflux. Upper esophageal sphincter (UES) contraction is mainly
      associated with liquid reflux during recumbent position and UES relaxation
      predominantly related with air reflux during upright position. The frequency of
      TLESR in GERD patients seems to be not different compared to normal individuals,
      but the refluxate of GERD patients tend to be more acidic during TLESR.

PMID- 22460569
TI  - [Clinicopathologic features of cases with negative pathologic results after
      endoscopic submucosal dissection].
AB  - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is accepted as a standard
      treatment of early gastric cancer (EGC) and gastric adenoma. Occasionally,
      tumorous lesion is not found and pathologic discrepancies can occur after ESD.
      The aim of this study was to analyze the factors affecting the negative
      pathologic results after ESD. METHODS: We retrospectively reviewed the data from
      all patients with gastric neoplasm (276 EGC and 516 gastric adenomas) who were
      treated with ESD during past 3 years and enrolled the patients who had negative
      pathologic results. RESULTS: Out of 792 patients treated with ESD, 27 patients
      (3.4%) were eligible for inclusion. Among the 27 patients, factors affecting the
      negative pathologic results were, most commonly, the focal lesion (n=13, 48.2%)
      which was small enough to be removed completely during pre-ESD biopsy, followed
      by pathologic discrepancies (n=11, 40.7%) between pathologists and lastly the
      operator factor (n=3, 11.1%) dissecting incorrect lesions. Of the focal lesions,
      the initial pathologic diagnoses were adenocarcinoma in 11 cases (84.6%). In
      cases with pathologic discrepancies, all the pretreatment diagnoses were adenoma
      with low grade dysplasia. In cases caused by operator factors, intestinal
      metaplasia was accompanied by elevated adenoma in all cases. CONCLUSIONS: To
      decrease negative pathologic results after ESD, an endoscopist should perform ESD
      after sufficient communication with pathologists, especially for adenoma with low
      grade dysplasia, and choose correct lesion, especially located at the antrum and
      associated with intestinal metaplasia. The possibility of total removal of small
      lesions even by forcep biopsy should be considered.

PMID- 22460570
TI  - Comparison of radiofrequency ablation and resection for hepatic metastasis from
      colorectal cancer.
AB  - BACKGROUND/AIMS: Radiofrequency ablation (RFA) has been mostly used as a
      therapeutic alternative to hepatic resection for treating liver metastasis of
      colorectal cancer. The purpose of the present study was to determine whether
      there were differences in outcome between RFA and surgical resection in the
      treatment of colorectal cancer with liver metastases. METHODS: We performed a
      retrospective analysis of 53 patients who underwent only hepatic resection or
      only RFA for colorectal liver metastases. Twenty-five patients who underwent
      hepatic resection were compared with 28 patients who underwent RFA for
      synchronous or metachronous liver metastases. RESULTS: The median CEA level at
      the time of diagnosis of liver metastases was significantly higher in the
      resection group (14.2 ng/mL vs. 2.8 ng/mL, p=0.002). The median size of main
      liver metastases was significantly larger in the resection group (4.0 cm vs. 2.05
      cm, p=0.002). There was no difference in the percentage of patients experiencing
      major complication (one patient in each group). The marginal recurrence rate was
      significantly higher in the RFA group (p=0.004). Disease-free and overall
      survival were longer in the resection group (p=0.008 and 0.017, respectively). In
      multivariate analysis, only the type of treatment was a factor associated with
      disease-free and overall survival (p=0.004 and 0.007, respectively). CONCLUSIONS:
      Because of the high marginal recurrence rate, RFA shows an inferior outcome in
      comparison with surgical resection. Therefore, RFA should be considered for only
      selected patients with unresectable (by any means) disease or with high operative
      risk.

PMID- 22460571
TI  - [Entecavir therapy for patients with hepatitis B virus-related decompensated
      cirrhosis].
AB  - BACKGROUND/AIMS: Entecavie (ETV) has a potent antiviral effect and low rates of
      resistance in hepatitis B virus (HBV) and is the first-line monotherapy in
      patients with HBV-related decompensated cirrhosis. We evaluated the efficacy of
      12 months treatment with ETV and tried to determine predictive factors of
      response. METHODS: Forty-five consecutive decompensated cirrhotic patients who
      received ETV (0.5 mg/day) for more than six months were included. All patients
      were positive for HBV DNA, and the Child-Turcotte-Pugh (CTP) scores were over 8
      point. Seventeen patients were HBeAg-positive. CTP score, model for end-stage
      liver disease (MELD) score, serum markers of liver function and HBV DNA were
      assessed every 3 months. RESULTS: ETV treatment for 12 months resulted in
      improvement of CTP and MELD scores. Pre-treatment mean CTP and MELD score were
      decreased from 10.1 (+/-2.0) and 13.48 (+/-4.05) to 7.24 (+/-2.0) and 9.68 (+/
      4.85) at 12 months, respectively. The 1-year cumulative rates of HBV DNA
      negativity and HBeAg loss were 88.9% and 52.9%, respectively, by intention-to
      treat analysis. Thirty-two (71.1%) showed improvement in CTP score. Eleven
      patients did not show change, and 2 patients got worse. The AST/ALT, albumin,
      bilrubin, prothrombin time were significantly normalized within six months. The
      good responder group had high level of prothrombin time than the poor responder
      group (p=0.004). CONCLUSIONS: Our result shows that entecavir can improve liver
      function in about 70% of patients with HBV related decompensated liver cirrhosis.
      INR may be a predictive factor of good response with entecavir in these patients.

PMID- 22460572
TI  - [Could nafamostat or gabexate prevent the post endoscopic retrograde
      cholangiopancreatography pancreatitis?].
AB  - BACKGROUND/AIMS: ERCP is the most common procedure for the diagnosis and
      treatment of bile duct and pancreatic disease, but Post-ERCP pancreatitis makes
      poor outcome in some cases. The protease inhibitors, nafamostat and gabexate,
      have been used to prevent pancreatitis related to ERCP, but there is some debate.
      We tried to evaluate the efficacy of gabexate and nafamostat for the prevention
      of post-ERCP pancreatitis. METHODS: Two hundred forty two patients (73 patients
      in the gabexate group, 88 patients in the nafamostat group and 81 patients in the
      placebo group) were included in the study after selective exclusion. The
      incidence of pancreatitis after ERCP was compared among groups. RESULTS: The
      incidence of pancreatitis were 6.8% in the gabexate group, 5.7% in the nafamostat
      group and 6.2% in the placebo group (p=0.954). CONCLUSIONS: There was no
      meaningful difference among the gabexate, nafamostat and placebo group.

PMID- 22460573
TI  - [A case of hypopharyngeal cancer treated by endoscopic submucosal dissection].
AB  - Recent advances in endoscopic instruments, including narrow-band imaging (NBI)
      and magnification endoscopy, allowed dramatic increase in the early diagnosis of
      hypopharyngeal cancers. In addition, endoscopic mucosal resection or endoscopic
      submucosal dissection has recently been used for the treatment of hypopharyngeal
      cancer at an early stage, especially in Japan. However, to date, there is no
      published report in Korea. A 68-year-old man was admitted for preoperative
      evaluation and treatment for known esophageal cancer initially diagnosed at a
      local clinic. During the evaluation, magnifying endoscopy combined with the NBI
      system revealed a concurrent hypopharyngeal cancer not detected by initial
      conventional endoscopy. In this case report, we describe for the first time in
      Korea a case of early stage hypopharyngeal carcinoma that was successfully
      treated by endoscopic submucosal dissection with a review of literature.

PMID- 22460574
TI  - [A case of idiopathic recurrent duodenojejunitis].
AB  - There are various etiologies of duodenojejunitis such as Henoch-Schonlei purpura
      (H-S purpura), vasculitis, Crohn's disease, celiac sprue, ischemia, lymphoma,
      Zollinger-Ellison syndrome, bacteria or parasite infection, radiation, drug
      induced jejunitis, eosinophilic jejunitis, and toxins. A 31-year-old man
      presented with left upper quadrant pain. He did not have febrile sense,
      hematochezia, melena, diarrhea, arthralgia and hematuria. He had neither drug
      history nor traveling history. Esophagogastroduodenoscopy showed diffuse mucosal
      erythema and segmental hemorrhagic erosions on the distal area to the descending
      portion of the duodenum and proximal jejunum, which were commonly observed in the
      gastrointestinal involvement of H-S purpura. However, he showed no skin lesions,
      joint and urologic problems until the discharge. Autoimmune markers such as
      antinuclear antibody and antineutrophil cytoplasmic antibody were negative.
      Celiac and mesenteric angiogram showed no vascular abnormality. After the
      administration of oral prednisolone 40 mg daily for therapeutic trial, abdominal
      pain and endoscopic lesions were improved. He experienced relapses of same
      episode without skin lesions 16 times during follow-up of 8 years, which were
      also treated with prednisolone. The abdominal computed tomography during the
      follow-up also showed no significant finding. We report a case of primary
      recurrent duodenojejunitis similar to the gastrointestinal involvement of H-S
      purpura without purpura.

PMID- 22460575
TI  - [A case of multiple gastrointestinal stromal tumor of the jejunum which was
      diagnosed by capsule endoscopy].
AB  - More than 90% cases of chronic gastrointestinal bleeding can be diagnosed by
      upper endoscopy and/or colonoscopy, and therefore, obscure gastrointestinal
      bleeding has been defined as bleeding of unknown origin that persists after these
      conventional endoscopic evaluation. Gastrointestinal stromal tumors (GISTs) are
      rare tumors, but the most common form of mesenchymal tumors of the
      gastrointestinal tract. Small bowel is the second most common primary site for
      GISTs, and accounts for 2-10% of chronic bleeding sites. GISTs usually present as
      a sporadic and solitary tumor, and a minority of the cases of multiple GISTs are
      discovered as forms of hereditary or idiopathic tumor syndromes. Small bowel
      tumor has been difficult to diagnose because of absence of accurate and proper
      diagnostic tools. Recently developed wireless capsule endoscopy helps in the
      diagnostic work-up of small bowel diseases. We report a case of multiple jejunal
      GISTs presenting melena in a 39-year-old male, which was diagnosed with wireless
      capsule endoscopy.

PMID- 22460576
TI  - A case of nonpolypoid cancer arising from colonic muco-submucosal elongated
      polyp.
AB  - A colonic muco-submucosal elongated polyp (CMSEP) was identified at colonoscopy
      in a 53-year-old male patient with lower gastrointestinal bleeding. Non-polypoid
      depressed type of early cancer was noted at the tip of the colonic polyp. The
      CMSEP is very rare and incidentally found in most cases. Moreover, its
      association with colonic neoplasia is extremely rare. To our knowledge, this is
      the second case report of CMSEP associated with a cancerous transformation.

PMID- 22460577
TI  - Tuning the coordination chemistry of a Cu(II) complex at high-pressure.
AB  - Application of pressure on the Cu-complex CuAsp causes Jahn-Teller Cu-O bonds to
      be compressed, increasing the coordination environment from [4 + 1] to [4 + 2],
      highlighted by a discontinuity on compression of these bonding interactions.

PMID- 22460578
TI  - Such small hands: the roles of centrins/caltractins in the centriole and in
      genome maintenance.
AB  - Centrins are small, highly conserved members of the EF-hand superfamily of
      calcium-binding proteins that are found throughout eukaryotes. They play a major
      role in ensuring the duplication and appropriate functioning of the ciliary basal
      bodies in ciliated cells. They have also been localised to the centrosome, which
      is the major microtubule organising centre in animal somatic cells. We describe
      the identification, cloning and characterisation of centrins in multiple
      eukaryotic species. Although centrins have been implicated in centriole
      biogenesis, recent results have indicated that centrosome duplication can, in
      fact, occur in the absence of centrins. We discuss these data and the non
      centrosomal functions that are emerging for the centrins. In particular, we
      discuss the involvement of centrins in nucleotide excision repair, a process that
      repairs the DNA lesions that are induced primarily by ultraviolet irradiation. We
      discuss how centrin may be involved in these diverse processes and contribute to
      nuclear and cytoplasmic events.

PMID- 22460579
TI  - Homeostatic and innate immune responses: role of the transmembrane glycoprotein
      CD98.
AB  - The transmembrane glycoprotein CD98 is a potential regulator of multiple
      functions, including integrin signaling and amino acid transport. Abnormal
      expression or function of CD98 and disruption of the interactions between CD98
      and its binding partners result in defects in cell homeostasis and immune
      responses. Indeed, expression of CD98 has been correlated with diseases such as
      inflammation and tumor metastasis. Modulation of CD98 expression and/or function
      therefore represents a promising therapeutic strategy for the treatment and
      prevention of such pathologies. Herein, we review the role of CD98 with focus on
      its functional importance in homeostasis and immune responses, which could help
      to better understand the pathogenesis of CD98-associated diseases.

PMID- 22460580
TI  - Homeostatic maintenance of T cells and natural killer cells.
AB  - Homeostasis in the immune system encompasses the mechanisms governing maintenance
      of a functional and diverse pool of lymphocytes, thus guaranteeing immunity to
      pathogens while remaining self-tolerant. Antigen-naive T cells rely on survival
      signals through contact with self-peptide-loaded major histocompatibility complex
      (MHC) molecules plus interleukin (IL)-7. Conversely, antigen-experienced (memory)
      T cells are typically MHC-independent and they survive and undergo periodic
      homeostatic proliferation through contact with both IL-7 and IL-15. Also, non
      conventional gammadelta T cells rely on a mix of IL-7 and IL-15 for their
      homeostasis, whereas natural killer cells are mainly dependent on contact with IL
      15. Homeostasis of CD4(+) T regulatory cells is different in being chiefly
      regulated by contact with IL-2. Notably, increased levels of these cytokines
      cause expansion of responsive lymphocytes, such as found in lymphopenic hosts or
      following cytokine injection, whereas reduced cytokine levels cause a decline in
      cell numbers.

PMID- 22460581
TI  - Signals controlling rest and reactivation of T helper memory lymphocytes in bone
      marrow.
AB  - Established views on the maintenance of immunological memory have been challenged
      recently by the description of memory plasma cells and memory T helper (Th)
      lymphocytes residing in the bone marrow (BM) in dedicated survival niches,
      resting in terms of proliferation and migration. While memory plasma cells are no
      longer reactive to antigen, memory Th lymphocytes are in a state of attentive
      rest, and can be reactivated fast and efficiently. Here, we discuss the signals
      controlling these resting states, which the memory lymphocytes receive from their
      microenvironment.

PMID- 22460582
TI  - Partial complementation of a DNA ligase I deficiency by DNA ligase III and its
      impact on cell survival and telomere stability in mammalian cells.
AB  - DNA ligase I (LigI) plays a central role in the joining of strand interruptions
      during replication and repair. In our current study, we provide evidence that DNA
      ligase III (LigIII) and XRCC1, which form a complex that functions in single
      strand break repair, are required for the proliferation of mammalian LigI
      depleted cells. We show from our data that in cells with either dysfunctional
      LigI activity or depleted of this enzyme, both LigIII and XRCC1 are retained on
      the chromatin and accumulate at replication foci. We also demonstrate that the
      LigI and LigIII proteins cooperate to inhibit sister chromatid exchanges but that
      only LigI prevents telomere sister fusions. Taken together, these results suggest
      that in cells with dysfunctional LigI, LigIII contributes to the ligation of
      replication intermediates but not to the prevention of telomeric instability.

PMID- 22460583
TI  - The physiological impact of microRNA gene regulation in the retina.
AB  - microRNAs (miRNAs) are small, stable RNA molecules that post-transcriptionally
      regulate gene expression in plants and animals by base pairing to partially
      complementary sequences on target mRNAs to inhibit protein synthesis. More than
      250 miRNAs are reportedly expressed in the retina, and miRNA gene regulation has
      been shown to affect retinal development, function, and disease. Here we
      highlight recent advances in understanding the functional roles of vertebrate
      retinal miRNAs. Details are emerging about the physiological impact of specific
      miRNAs in the developing and mature retina, and we discuss a group of emerging
      technologies for studying miRNAs, which can be employed to yield a deeper
      understanding of retinal miRNA gene regulation.

PMID- 22460585
TI  - Function-preserving therapy for jugulotympanic paragangliomas: a retrospective
      analysis from 2000 to 2010.
AB  - OBJECTIVES/HYPOTHESIS: Treatment for jugulotympanic paragangliomas (JTPs) is
      shifting from radical toward function-preserving surgery. Alternative primary
      treatments are available, such as stereotactic radiotherapy (SRT) and
      radiosurgery. The aim of this study was to analyze the results after primary
      function-preserving surgery with or without adjuvant radiotherapy, or primary
      SRT, in the treatment of JTPs. STUDY DESIGN: Retrospective analysis. METHODS:
      From 2000 to 2010, 45 patients (mean age, 62.5 years) received function
      preserving treatment for JTPs-four type A paragangliomas (8.9%), 19 type B
      (42.2%), 13 type C (28.9%), and nine type D (20%) in the Fisch classification.
      The patients were retrospectively assigned to three groups: primary function
      preserving surgery, primary stereotactic radiotherapy, and close follow-up. The
      end points for analysis were long-term tumor control, cranial nerve function, and
      hearing. RESULTS: A total of 64.4% of the patients (n = 29) received primary
      surgery, with complete resection in 18. Eleven patients had surgical tumor
      reduction, with fractionated postoperative radiotherapy (mean 53.5 Gy; range, 50
      56 Gy) in five cases and radiosurgery (18 Gy) in one case; five patients received
      close follow-up. Twelve patients (26.7%) underwent primary radiotherapy (11 with
      SRT [mean, 50 Gy]; one with radiosurgery [16 Gy]). Four patients (8.9%) received
      a wait-and-scan strategy. The mean follow-up was 46.8 months. The overall tumor
      control rate was 97.2%. CONCLUSIONS: With these high tumor control rates,
      consistent with the literature, function-preserving therapy for JTPs currently
      appears to offer the greatest benefit for patients.

PMID- 22460584
TI  - Unraveling the genetic underpinnings of myeloproliferative neoplasms and
      understanding their effect on disease course and response to therapy: proceedings
      from the 6th International Post-ASH Symposium.
AB  - Immediately after the annual scientific meeting of the American Society of
      Hematology (ASH), a select group of clinical and laboratory investigators in
      myeloproliferative neoplasms (MPN) is summoned to a post-ASH conference on
      chronic myeloid leukemia and the BCR-ABL1-negative MPN. The 6th such meeting
      occurred on December 13-14,2011, in La Jolla, California, USA, under the
      direction of its founder,Dr. Tariq Mughal. The current document is the first of
      two reports on this post-ASH event and summarizes the most recent preclinical and
      clinical advances in polycythemia vera, essential thrombocythemia,and primary
      myelofibrosis.

PMID- 22460586
TI  - Outcome of MRI-based intravenous thrombolysis in carotid-T occlusion.
AB  - Low recanalization rates and poor clinical outcome have been reported after
      intravenous thrombolysis (IV-tPA) in carotid-T occlusion (CTO). We studied
      clinical outcome and imaging findings of MRI-based intravenous thrombolysis in
      CTO. Data of patients with acute ischemic stroke and CTO treated with IV-tPA
      within 6 h of symptom onset based on MRI criteria were retrospectively analyzed.
      Vessel occlusion was defined based on MR angiography. Acute diffusion and
      perfusion lesion volumes and final infarct volumes after 3-7 days were
      delineated. The National Institutes of Health Stroke Scale (NIHSS) was used to
      assess the neurological deficit on admission. Recanalization was evaluated after
      24 h. Clinical outcome was assessed using the modified Rankin Scale (mRS) after
      90 days. Clinical and imaging data were compared to patients with middle cerebral
      artery main stem occlusion (MCAO). A total of 20 patients with CTO and 51
      patients with MCAO were studied. Onset to treatment time, NIHSS on admission,
      initial diffusion and perfusion lesion volumes, and recanalization rates after 24
      h were similar between groups. Final infarct volume was larger for CTO (82 vs. 30
      ml, p = 0.006). Although overall outcome was not significantly different between
      groups (p = 0.251), independent outcome (mRS 0-2) tended to be less frequent in
      CTO (17 vs. 39 %), while poor outcome (mRS 4-6) appeared more common (72 vs. 43
      %). The proportion of patients with good clinical outcome after intravenous
      thrombolysis in CTO is small. Moreover, final infarct volume is larger and
      clinical outcome appears to be worse compared to MCAO.

PMID- 22460588
TI  - Wheels within wheels: multifocal autoimmune myelitis in a woman with Huntington's
      disease.

PMID- 22460587
TI  - Comparison of clinical characteristics between familial and non-familial early
      onset Alzheimer's disease.
AB  - Although familial Alzheimer's disease (FAD) is an early onset AD (EAD), most
      patients with EAD do not have a familial disorder. Recent guidelines recommend
      testing for genes causing FAD only in those EAD patients with two first-degree
      relatives. However, some patients with FAD may lack a known family history or
      other indications for suspecting FAD but might nonetheless be carriers of FAD
      mutations. The study was aimed to identify clinical features that distinguish FAD
      from non-familial EAD (NF-EAD). A retrospective review of a university-based
      cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted.
      The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of
      disease onset (41.8 +/- 5.2 vs. 55.9 +/- 4.8 years) and, at initial assessment, a
      longer disease duration (5.1 +/- 3.4 vs. 3.3 +/- 2.6 years) and lower MMSE scores
      (10.74 +/- 8.0 vs. 20.95 +/- 5.8). Patients with NF-EAD were more likely to
      present with non-memory deficits, particularly visuospatial symptoms, than were
      FAD patients. When age, disease duration, and MMSE scores were controlled in a
      logistical regression model, FAD patients were more likely to have significant
      headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with
      NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1
      mutations differed from those with NF-EAD by a history of headaches and
      pseudobulbar affect, as well as myoclonus and gait abnormality on examination.
      These may represent differences in pathophysiology between FAD and NF-EAD and in
      some contexts such findings should lead to genetic counseling and appropriate
      recommendations for genetic testing for FAD.

PMID- 22460590
TI  - An efficient lipase-catalyzed enantioselective hydrolysis of (R,S)-azolides
      derived from N-protected proline, pipecolic acid, and nipecotic acid.
AB  - In the Candida antarctica lipase B-catalyzed hydrolysis of (R,S)-azolides derived
      from (R,S)-N-protected proline in water-saturated methyl tert-butyl ether (MTBE),
      high enzyme activity with excellent enantioselectivity (V (S) V (R) (-1) > 100)
      for (R,S)-N-Cbz-proline 1,2,4-triazolide (1) and (R,S)-N-Cbz-proline 4
      bromopyrazolide (2) was exploited in comparison with their corresponding methyl
      ester analog (3). Changing of the substrate structure, water content, solvent,
      and temperature was found to have profound influences on the lipase performance.
      On the basis of enzyme activity and enantioselectivity and solvent boiling point,
      the best reaction condition of using 1 as the substrate in water-saturated MTBE
      at 45  degrees C was selected and further employed for the successful resolution
      of (R,S)-N-Cbz-pipecolic 1,2,4-triazolide (5) and (R,S)-N-Boc-nipecotic 1,2,4
      triazolide (9). Moreover, more than 89.1 % recovery of remained (R)-1 is
      obtainable in five cycles of enzyme reusage, when pH 7 phosphate buffers were
      employed as the extract at 4  degrees C.

PMID- 22460589
TI  - Overproduction and easy recovery of target gene products from cyanobacteria,
      photosynthesizing microorganisms.
AB  - New cyanobacterial expression vectors, possessing an origin of replication that
      functions in a broad range of Gram-negative bacteria, were constructed. To
      inspect the shuttle vectors, the gene gfp was cloned downstream from the
      expression control element (ECE) originating from the regulatory region of the
      Microcystis aeruginosa gene psbA2 (for photosystem II D1 protein), and the
      vectors were introduced into three kinds of cyanobacteria (Synechocystis sp. PCC
      6803, Synechococcus elongatus PCC 7942, and Limnothrix/Pseudanabaena sp. ABRG5-3)
      by conjugation. Multiple copy numbers of the expression vectors (in the range of
      14-25 copies per cell) and a high expression of green fluorescent protein (GFP)
      at the RNA/protein level were observed in the cyanobacterial transconjugants.
      Importantly, GFP was observed in a supernatant from the autolysed transconjugants
      of ABRG5-3 and easily collected from the supernatant without centrifugation
      and/or further cell lysis. These results indicate the vectors together with the
      recombinant cells to be useful for overproducing and recovering target gene
      products from cyanobacteria.

PMID- 22460591
TI  - Downstream reactions and engineering in the microbially reconstituted pathway for
      Taxol.
AB  - Taxol (a trademarked product of Bristol-Myers Squibb) is a complex isoprenoid
      natural product which has displayed potent anticancer activity. Originally
      isolated from the Pacific yew tree (Taxus brevifolia), Taxol has been mass
      produced through processes reliant on plant-derived biosynthesis. Recently, there
      have been alternative efforts to reconstitute the biosynthetic process through
      technically convenient microbial hosts, which offer unmatched growth kinetics and
      engineering potential. Such an approach is made challenging by the need to
      successfully introduce the significantly foreign enzymatic steps responsible for
      eventual biosynthesis. Doing so, however, offers the potential to engineer more
      efficient and economical production processes and the opportunity to design and
      produce tailored analog compounds with enhanced properties. This mini review will
      specifically focus on heterologous biosynthesis as it applies to Taxol with an
      emphasis on the challenges associated with introducing and reconstituting the
      downstream reaction steps needed for final bioactivity.

PMID- 22460592
TI  - Enhancement of photoheterotrophic biohydrogen production at elevated temperatures
      by the expression of a thermophilic clostridial hydrogenase.
AB  - The working temperature of a photobioreactor under sunlight can be elevated above
      the optimal growth temperature of a microorganism. To improve the biohydrogen
      productivity of photosynthetic bacteria at higher temperatures, a [FeFe]
      hydrogenase gene from the thermophile Clostridium thermocellum was expressed in
      the mesophile Rhodopseudomonas palustris CGA009 (strain CGA-CThydA) using a log
      phase expression promoter P( pckA ) to drive the expression of heterogeneous
      hydrogenase gene. In contrast, a mesophilic Clostridium acetobutylicum [FeFe]
      hydrogenase gene was also constructed and expressed in R. palustris (strain CGA
      CAhydA). Both transgenic strains were tested for cell growth, in vivo hydrogen
      production rate, and in vitro hydrogenase activity at elevated temperatures.
      Although both CGA-CThydA and CGA-CAhydA strains demonstrated enhanced growth over
      the vector control at temperatures above 38  degrees C, CGA-CThydA produced more
      hydrogen than the other strains. The in vitro hydrogenase activity assay,
      measured at 40  degrees C, confirmed that the activity of the CGA-CThydA
      hydrogenase was higher than the CGA-CAhydA hydrogenase. These results showed that
      the expression of a thermophilic [FeFe]-hydrogenase in R. palustris increased the
      growth rate and biohydrogen production at elevated temperatures. This transgenic
      strategy can be applied to a broad range of purple photosynthetic bacteria used
      to produce biohydrogen under sunlight.

PMID- 22460593
TI  - Production and characterisation of recombinant alpha-L-arabinofuranosidase for
      production of xylan hydrogels.
AB  - A recombinant strain of the protease-deficient, non-acidifying pH mutant
      Aspergillus niger D15 (A. niger D15 [abfB]) strain was developed to secrete alpha
      L-arabinofuranosidase (AbfB) free of endo-1,4-beta-xylanases for selective
      hydrolysis of xylan into hydrogels. The A. niger D15 [abfB] strain expressed the
      alpha-L-arabinofuranosidase abfB gene under the transcriptional control of the
      glyceraldehyde-3-phosphate dehydrogenase promoter (gpd(P)) and glucoamylase
      terminator (glaA(T)) in fermentation cultures containing 10 % glucose. The yield,
      activity, purity, kinetics and ability of the recombinant AbfB to selectively
      hydrolyse xylans into hydrogels were assessed. The recombinant AbfB secreted in
      125-mL shake flasks and 10-L bioreactor fermentation cultures had specific
      activities against rho-nitrophenyl-alpha-arabinofuranoside of up to 4.4 and 2.7 U
      g-1 (dry weight), respectively. In addition, the recombinant AbfB was present as
      a single protein species on silver-stained 10 % sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. The recombinant AbfB had optimal activity at
      40-55  degrees C and pH 3.0 to pH 5.0 and was stable at temperature and pH of up
      to 60  degrees C and pH 6.0, respectively. About 20 % of the available arabinose
      in the xylan was released by the recombinant AbfB from the hydrolysis of low
      viscosity wheat and oat spelt arabinoxylans and about 9 and 5 % from bagasse and
      bamboo arabinoglucuronoxylans, respectively, that led to the formation of the
      hydrogels. Therefore, the constructed A. niger D15 [abfB] strain presented a
      microbial system for the production of recombinant AbfB with the required purity
      for the modification of xylans into hydrogels.

PMID- 22460594
TI  - Nanostructured metal oxide-based materials as advanced anodes for lithium-ion
      batteries.
AB  - The search for new electrode materials for lithium-ion batteries (LIBs) has been
      an important way to satisfy the ever-growing demands for better performance with
      higher energy/power densities, improved safety and longer cycle life.
      Nanostructured metal oxides exhibit good electrochemical properties, and they are
      regarded as promising anode materials for high-performance LIBs. In this feature
      article, we will focus on three different categories of metal oxides with
      distinct lithium storage mechanisms: tin dioxide (SnO(2)), which utilizes
      alloying/dealloying processes to reversibly store/release lithium ions during
      charge/discharge; titanium dioxide (TiO(2)), where lithium ions are
      inserted/deinserted into/out of the TiO(2) crystal framework; and transition
      metal oxides including iron oxide and cobalt oxide, which react with lithium ions
      via an unusual conversion reaction. For all three systems, we will emphasize that
      creating nanomaterials with unique structures could effectively improve the
      lithium storage properties of these metal oxides. We will also highlight that the
      lithium storage capability can be further enhanced through designing advanced
      nanocomposite materials containing metal oxides and other carbonaceous supports.
      By providing such a rather systematic survey, we aim to stress the importance of
      proper nanostructuring and advanced compositing that would result in improved
      physicochemical properties of metal oxides, thus making them promising negative
      electrodes for next-generation LIBs.

PMID- 22460595
TI  - Bioavailability and in vivo efficacy of a praziquantel-polyvinylpyrrolidone solid
      dispersion in Schistosoma mansoni-infected mice.
AB  - One of the problems of praziquantel (PZQ) is its very low aqueous solubility.
      Moreover, its dissolution rate is considered the limiting factor for its
      bioavailability. This work correlates the physical properties and the dissolution
      behavior of PZQ-polyvinylpyrrolidone (PVP) solid dispersion (SD) at the ratios of
      1:1 and 3:7 with its oral bioavailability and its in vivo efficacy against
      Schistosoma mansoni (S. mansoni). The PZQ and PZQ-PVP SD were characterized by
      infrared spectroscopy, differential scanning calorimetry, scanning electron
      microscopy (SEM) and solubility test. Results showed a decrease in crystallinity,
      possible interaction between PZQ and PVP, greater increase in dissolution rate
      and appreciable reduction in particle size. S. mansoni-infected mice treated
      orally with either pure PZQ or PZQ-PVP at a single dose of 500 mg/kg showed a
      higher increase in AUC((0-8h)), C (max), K(a) and t (1/2e) with a significant
      decrease in k (el) versus the corresponding uninfected mice. Moreover, uninfected
      and infected mice treated with PZQ-PVP SD showed 2.3-, 1.6- and 1.3-, 1.25-fold
      increase, respectively, in AUC((0-8h)) and C(max), with a decrease in k(el) and
      increase in t (1/2e) by twofold versus the corresponding pure PZQ-treated groups.
      Percentage worm reduction at all administered doses (62.5, 125, 250, 500 and
      1,000 mg/kg) was significantly higher (1- to 1.5-fold) in mice treated with PZQ
      PVP SD (ED50 = 40.92) versus those treated with pure PZQ (ED50 = 99.29). In
      addition, a significant reduction in total tissue egg load concomitant with a
      significant decrease in total immature and mature eggs and an increase in dead
      eggs in PZQ-PVP SD-treated groups versus their corresponding pure PZQ-treated
      groups was recorded. Solid dispersion of PZQ with PVP could lead to a further
      improvement in the effectiveness of PZQ therapy especially with the appearance of
      some PZQ-tolerant S. mansoni isolates.

PMID- 22460596
TI  - Comparison of the pharmacokinetics of sulfamethoxazole in native Han and Tibetan
      male Chinese volunteers living at high altitude.
AB  - The aim of this study was to investigate the pharmacokinetics of sulfamethoxazole
      in native Han and Tibetan healthy Chinese subjects living chronically at high
      altitude. An open-labeled, controlled, prospective study was conducted in healthy
      Chinese male volunteers. Sulfamethoxazole 1,200 mg was administered orally to two
      groups: native Han and Tibetan volunteers living at high altitude (2,500-3,900 m
      [8,200-12,800 ft]). Blood samples were collected from an indwelling venous
      catheter into heparinized tubes before (baseline) study drug administration and
      at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h after study drug
      administration. Sulfamethoxazole in whole blood, plasma, and plasma water, and
      metabolite N (4)-acetyl-sulfamethoxazole in plasma were determined by HPLC.
      Tolerability was determined using blood chemistry testing, continuous 12-lead
      electrocardiogram, and blood pressure monitoring. The protein binding was
      significantly higher in the native Tibetan group (70.5 %) compared to the native
      Han group (67.3 %) (p < 0.05). The binding of sulfamethoxazole to red blood cells
      was 7.4 and 8.3 % in the native Han and native Tibetan groups, respectively.
      There was no significant difference between the two groups. The AUC(0-infinity)
      was significantly lower in the native Tibetan group compared to the native Han
      group (p < 0.05), and other pharmacokinetics parameters were found to have no
      significant difference between the two groups. This study found little changes in
      the disposition of sulfamethoxazole in these native healthy Tibetan Chinese
      subjects living at high altitude in comparison to native healthy Han Chinese
      subjects living at high altitude.

PMID- 22460598
TI  - Neonatology enters the 21st century for health care oversight: the public
      reporting of health care outcomes.

PMID- 22460597
TI  - Power comparison of admixture mapping and direct association analysis in genome
      wide association studies.
AB  - When dense markers are available, one can interrogate almost every common variant
      across the genome via imputation and single nucleotide polymorphism (SNP) test,
      which has become a routine in current genome-wide association studies (GWASs). As
      a complement, admixture mapping exploits the long-range linkage disequilibrium
      (LD) generated by admixture between genetically distinct ancestral populations.
      It is then questionable whether admixture mapping analysis is still necessary in
      detecting the disease associated variants in admixed populations. We argue that
      admixture mapping is able to reduce the burden of massive comparisons in GWASs;
      it therefore can be a powerful tool to locate the disease variants with
      substantial allele frequency differences between ancestral populations. In this
      report we studied a two-stage approach, where candidate regions are defined by
      conducting admixture mapping at stage 1, and single SNP association tests are
      followed at stage 2 within the candidate regions defined at stage 1. We first
      established the genome-wide significance levels corresponding to the criteria to
      define the candidate regions at stage 1 by simulations. We next compared the
      power of the two-stage approach with direct association analysis. Our simulations
      suggest that the two-stage approach can be more powerful than the standard genome
      wide association analysis when the allele frequency difference of a causal
      variant in ancestral populations, is larger than 0.4. Our conclusion is
      consistent with a theoretical prediction by Risch and Tang ([2006] Am J Hum Genet
      79:S254). Surprisingly, our study also suggests that power can be improved when
      we use less strict criteria to define the candidate regions at stage 1.

PMID- 22460599
TI  - Subgaleal hemorrhage in a neonate with factor X deficiency following a non
      traumatic cesarean section.
AB  - This case report describes a term infant born by a non-traumatic, non
      instrumented cesarean section that presented with respiratory failure and severe
      metabolic acidosis secondary to subgaleal hemorrhage (SGH). Further evaluation
      revealed a functional factor X deficiency that was initially treated with fresh
      frozen plasma infusions. This report is significant for the occurrence of a SGH
      in a non-traumatic delivery and emphasizes the importance of obtaining a
      coagulopathy evaluation in patients with similar presentations. In addition, this
      case suggests that the mechanism of injury that causes SGH may occur more
      frequently than previously thought, but does not become clinically significant in
      patients without an underlying coagulopathy.

PMID- 22460600
TI  - Monozygotic twins discordant for trisomy 13.
AB  - Monozygotic twins with discordant karyotypes are rare. We report a case of
      monozygotic twins discordant for trisomy 13 by amniocyte karyotypes. Ultrasound
      revealed multiple congenital anomalies in Twin A (47,XY,+13), none in Twin B
      (46,XY), and monochorionic-diamniotic placentation. Zygosity testing performed
      both prenatally and after birth supported monozygosity. Twin A died in the
      neontal period. Twin B survived and had normal physical examination, but
      peripheral blood karyotype revealed 20% mosaicism for trisomy 13. Monochorionic
      diamniontic placentation with vascular anastomoses was confirmed by pathological
      examination. In this paper, we discuss the various mechanisms by which
      monozygotic twins may have discordant karyotypes. The surviving twin,
      structurally and developmentally normal at 6 months of age, will be monitored for
      potential complications of uniparental disomy of chromosome 13 and trisomy 13
      mosaicism.

PMID- 22460601
TI  - Type 2 CPAM with delayed-onset Bochdalek hernia.

PMID- 22460602
TI  - Haptoglobin in diagnosis of sepsis.

PMID- 22460604
TI  - Nanopatterning of Si(001) for bottom-up fabrication of nanostructures.
AB  - The epitaxial growth of Si on Si(001) under conditions at which the (2 * n)
      superstructure is forming has been investigated by scanning tunneling microscopy
      and Monte Carlo simulations. Our experiments reveal a periodic change of the
      surface morphology with the surface coverage of Si. A regular (2 * n) stripe
      pattern is observed at coverages of 0.7-0.9 monolayers that periodically
      alternates with less dense surface structures at lower Si surface coverages. The
      MC simulations show that the growth of Si is affected by step-edge barriers,
      which favors the formation of a rather uniform two-dimensional framework-like
      configuration. Subsequent deposition of Ge onto the (2 * n) stripe pattern yields
      a dense array of small Ge nanostructures.

PMID- 22460605
TI  - Synthesis and growth mechanism of multilayer TiO2 nanotube arrays.
AB  - High-aspect-ratio TiO(2) nanotube arrays formed by anodic oxidation have drawn
      extensive attention due to their easy fabrication and various excellent optical,
      electrical and biomedical properties. In contrast to conventional single-layer
      TiO(2) nanotubes prepared via constant-voltage anodization, we synthesize
      multilayer TiO(2) nanotube arrays with high surface area by using alternating
      voltage anodization steps. This work presents synthesis and growth mechanisms of
      single-layer smooth TiO(2) nanotubes, bamboo-type nanotubes and double-layer
      nanotubes, by tuning various parameters such as voltage, time, and water content
      in the electrolyte. It is found that ion diffusion inside the nanotubes dominates
      growth of these three structures. A stable pH and ion-diffusion profile allows
      the steady growth of smooth TiO(2) tubes in NH(4)F-containing ethylene glycol
      (EG). The addition of a low-voltage anodization step reduces the pH and ion
      diffusion gradient in the nanotubes and induces formation of bamboo-type
      nanotubes and double-layer nanotubes when a second high-voltage anodization is
      conducted. Ion diffusion through a nanotube takes time; thus formation of lower
      layer TO(2) nanotubes costs more time if longer nanotubes are grown in the upper
      layer, since ions diffuse through these longer nanotubes. This ion-diffusion
      controlled growth mechanism is further confirmed by tailoring the water content
      (0-20 vol%) in the electrolyte and the voltage gaps to control the time needed
      for initiation of lower-layer TiO(2) nanotube arrays. The fundamental
      understanding of the growth characteristics of double-layer TiO(2) nanotubes
      presented in this paper offers us more flexibility in engineering morphology,
      tuning dimensions and phase compositions of multilayer TiO(2) nanotubes. In
      addition, we synthesize double-layer TiO(2) nanotube arrays composed of one layer
      of anatase phase and another layer of amorphous phase.

PMID- 22460606
TI  - Prioritization of SNPs for genome-wide association studies using an interaction
      model of genetic variation, gene expression, and trait variation.
AB  - The identification of true causal loci to unravel the statistical evidence of
      genotype-phenotype correlations and the biological relevance of selected single
      nucleotide polymorphisms (SNPs) is a challenging issue in genome-wide association
      studies (GWAS). Here, we introduced a novel method for the prioritization of SNPs
      based on p-values from GWAS. The method uses functional evidence from
      populations, including phenotype-associated gene expressions. Based on the
      concept of genetic interactions, such as perturbation of gene expression by
      genetic variation, phenotype and gene expression related SNPs were prioritized by
      adjusting the p-values of SNPs. We applied our method to GWAS data related to
      drug-induced cytotoxicity. Then, we prioritized loci that potentially play a role
      in druginduced cytotoxicity. By generating an interaction model, our approach
      allowed us not only to identify causal loci, but also to find intermediate nodes
      that regulate the flow of information among causal loci, perturbed gene
      expression, and resulting phenotypic variation.

PMID- 22460607
TI  - An interaction-dominant perspective on reading fluency and dyslexia.
AB  - The background noise of response times is often overlooked in scientific
      inquiries of cognitive performances. However, it is becoming widely acknowledged
      in psychology, medicine, physiology, physics, and beyond that temporal patterns
      of variability constitute a rich source of information. Here, we introduce two
      complexity measures (1/f scaling and recurrence quantification analysis) that
      employ background noise as metrics of reading fluency. These measures gauge the
      extent of interdependence across, rather than within, cognitive components. In
      this study, we investigated dyslexic and non-dyslexic word-naming performance in
      beginning readers and observed that these complexity metrics differentiate
      reliably between dyslexic and average response times and correlate strongly with
      the severity of the reading impairment. The direction of change in the introduced
      metrics suggests that developmental dyslexia resides from dynamical instabilities
      in the coordination among the many components necessary to read, which could
      explain why dyslexic readers score below average on so many distinct tasks and
      modalities.

PMID- 22460608
TI  - Cognitive behavior therapy for chronic insomnia in occupational health services.
AB  - INTRODUCTION: The aim of this study was to examine the implementation and
      effectiveness of a cognitive behavioral group intervention model for chronic
      insomnia (CBT-I) in occupational health services (OHS). We also studied if
      insomnia symptoms and intervention effects differed on work days and days off.
      METHODS: The study design was a non-randomized group intervention, including a
      waiting period prior to CBT as a control condition. We followed up the results
      for a period of 6 months. Outcomes were assessed using a sleep diary,
      questionnaires, and actigraphy. The CBT-I groups were led by trained OHS nurses.
      RESULTS: A total of 26 participants completed the study. The intervention
      improved significantly participants' different self-reported sleep variables,
      perceived severity of insomnia, sleep-related dysfunctional cognitions, and
      psychiatric and somatic symptoms. The effects lasted, and partly increased during
      the follow-up. The participants generally slept significantly better on days off
      than on work days, but the treatment improved sleep on both. CONCLUSIONS: The
      study showed that a non-pharmacological treatment of insomnia can be implemented
      into OHS with a reasonable amount of effort and that the treatment delivered by
      trained OHS nurses yields promising results. These findings, however, need to be
      interpreted cautiously, due to the non-randomized design and small sample size.

PMID- 22460609
TI  - Effects of lexical-semantic treatment on memory in early Alzheimer disease: an
      observer-blinded randomized controlled trial.
AB  - BACKGROUND: Episodic memory and semantic abilities deteriorate early in Alzheimer
      disease (AD). Since the cognitive system includes interconnected and reciprocally
      influenced neuronal networks, the authors hypothesized that stimulation of
      lexical-semantic abilities may benefit semantically structured episodic memory.
      OBJECTIVE: To investigate the effects of lexical-semantic stimulation (LSS) on
      verbal communication and episodic memory in early AD. METHODS: Forty AD
      participants were randomized to LSS or unstructured cognitive stimulation (UCS)
      as control condition. Treatments lasted 3 months, 2 sections a week. The primary
      outcome measures were the Mini-Mental State Examination (MMSE), Boston Naming
      Test (BNT), Verbal Naming Test (VNT), Phonemic and Semantic Fluency, Story
      Recall, and Rey Auditory Verbal Learning (RAVL). Secondary outcome measures were
      neuropsychological tests assessing cognitive functions not stimulated by the
      intervention, such as attention, executive functions, and visual-spatial
      abilities, and the instrumental activities of daily living scale. A 6-month
      follow-up assessment was administered to the LSS group. RESULTS: LSS treatment
      yielded significant improvements of the MMSE, BNT, VNT, Brief Story Recall, and
      RAVL delayed recall mean scores. Among secondary outcome measures, only working
      memory and the speed of a task assessing executive functions (Stroop test)
      improved after LSS. Unstructured cognitive stimulation intervention did not
      improve any cognitive domain. Six months after LSS discontinuation, the MMSE mean
      score remains significantly higher than the baseline value. CONCLUSION: LSS
      treatment may improve episodic memory in AD patients and may be regarded as a
      clinical option to counteract the cognitive decline typical of the disease.

PMID- 22460610
TI  - Amount of exercise in the first week after stroke predicts walking speed and
      unassisted walking.
AB  - BACKGROUND: Predicting walking outcomes poststroke is a challenge for clinicians.
      OBJECTIVE: To identify the extent to which exercise dose (repetitions of leg
      movements) in the first week of a comprehensive stroke unit stay predicts
      discharge mobility. METHODS: A cohort study was conducted on 200 consecutive
      people admitted to a comprehensive stroke unit who required physical therapy.
      RESULTS: Discharge and predictor data were available for 191 survivors (99%). On
      admission, 86 participants were able to walk, and the average walking velocity
      was 0.42 m/s. On discharge, the average walking velocity was 0.77 m/s, and 152
      participants were able to walk. A discharge walking velocity of greater than 0.8
      m/s was predicted by the exercise dose achieved in the first week after
      admission. Adding other predictors did not significantly increase the predictive
      ability of the model. Completion of more than the median number of exercise
      repetitions (703) in the first week of admission was associated with a quicker
      recovery of unassisted walking. This effect persisted after adjustment for
      walking velocity on admission, cognition, and comorbidity. CONCLUSION: Exercise
      dose in the first week after admission for stroke is an important indicator of
      walking speed at discharge and the time to achieve unassisted walking.

PMID- 22460611
TI  - Spinal cord injury: one-year evolution of motor-evoked potentials and recovery of
      leg motor function in 255 patients.
AB  - BACKGROUND: The description of the natural course of recovery from a spinal cord
      injury (SCI) with spontaneous improvement of neurological, neurophysiological,
      and functional measures is an important prerequisite in appraising effects of
      upcoming interventional therapies. OBJECTIVE: To describe the spontaneous
      evolution of motor-evoked potentials of the anterior tibial muscle (TA-MEP) and
      their relation to outcomes of lower extremity motor scores (LEMS) and walking
      function in patients recovering from an acute SCI. METHODS: TA-MEPs were assessed
      in 255 SCI subjects within 5 time intervals throughout the first year after SCI
      with combined neurological and functional measures. Tibial nerve conduction
      studies were performed to screen for peripheral nerve damage. RESULTS: TA-MEP
      allowed stratification of SCI according to lesion severity and outcome. As MEP
      amplitudes increased over 12 months after SCI, this was paralleled by a
      significant improvement of LEMS and walking function. TA-MEP latencies remained
      usually stable. CONCLUSION: Clinical outcome and walking function after SCI can
      be predicted independent of clinical measures by assessment of TA-MEP reflecting
      corticospinal tract integrity.

PMID- 22460612
TI  - Referral to rehabilitation after severe traumatic brain injury: results from the
      PariS-TBI Study.
AB  - BACKGROUND: After a severe traumatic brain injury (TBI), some patients are
      discharged home without rehabilitation, although rehabilitation is assumed to
      improve outcome. OBJECTIVE: To assess factors that predict referral to
      rehabilitation following acute care. This study is part of a larger inception
      cohort study assessing the care network in the Parisian area (France). METHODS:
      Between July 2005 and April 2007, 504 adults with severe TBI (Glasgow Coma Scale
      score <= 8) were prospectively recruited by mobile emergency services. This study
      included 254 acute care survivors (80% male, median age 32 years). Data regarding
      demographics, injury severity, and acute care pathway were collected. The first
      analysis compared patients referred to a rehabilitation facility with patients
      discharged to a living place. The second analysis compared patients referred to a
      specialized neurorehabilitation (NR) facility with patients referred to
      nonspecialized rehabilitation. Univariate and multivariate statistics were
      computed. RESULTS: . In all, 162 patients (64%) were referred to rehabilitation,
      115 (45%) of which were referred to NR and 47 (19%) to nonspecialized
      rehabilitation. The following factors were significantly predictive of
      nonreferral to rehabilitation: living alone, a lower income professional
      category, pretraumatic alcohol abuse, lower TBI severity, and transfer through a
      nonspecialized medical ward before discharge. Patients referred to specialized NR
      were significantly younger and from a higher income professional category.
      CONCLUSIONS: These results raise concern regarding care pathways because many
      patients were discharged to living places, probably without adequate assessment
      and management of rehabilitation needs. Injury severity and social
      characteristics influenced discharge destination.

PMID- 22460614
TI  - If it's broken, fix it!

PMID- 22460613
TI  - Beraprost sodium, a stable prostacyclin analogue, improves insulin resistance in
      high-fat diet-induced obese mice.
AB  - Obesity induces hypertrophy of adipocyte resulting in production of pro
      inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and
      monocyte chemoattractant protein 1 (MCP1 (CCL2)). These cytokines play an
      important role in the development of insulin resistance. Beraprost sodium (BPS),
      a prostaglandin I2 analogue, is reported to attenuate inflammation. In this
      study, we examined the effect of BPS on glucose metabolism in mice fed a high-fat
      diet (HFD). Four-week-old C57/B6 male mice were fed a HFD for 12 weeks (HFD
      group) and the treatment group received oral BPS (300 MUg/kg per day) for the
      same period. Then, glucose metabolism, histological changes, and gene expression
      of white adipose tissue (WAT) were examined. Body weight was increased, and
      glucose intolerance and insulin resistance were developed in the HFD group.
      Treatment with BPS improved glucose tolerance and insulin action without body
      weight change. Histological analysis of WAT showed an increase in the size of
      adipocyte and macrophage infiltration in the HFD group, which was attenuated by
      BPS treatment. BPS reduced HFD-induced expression of MCP1 and TNF-alpha in WAT.
      BPS also attenuated hepatic steatosis induced by the HFD. These results suggest
      that BPS improved glucose intolerance possibly through suppression of
      inflammatory cytokines in WAT. BPS may be beneficial for the treatment of obesity
      associated glucose intolerance.

PMID- 22460615
TI  - Disparities in breast cancer mortality trends in a middle income country.
AB  - In recent decades, breast cancer cases have increased steadily worldwide.
      However, the increases do not hold across all demographics and breast cancer
      cases in low and middle income countries have increased much faster than the
      global trend. Colombia is not an exception. Breast cancer was the most frequent
      tumor and the second cause of cancer-related deaths in women in 2008, with an
      estimated of 6,700 new cases and 2,100 deaths. We present here an analysis of
      breast cancer mortality rates and trends in Colombia, over the period 1985-2008.
      We studied overall and age-specific changes in breast cancer mortality using
      change-point Poisson regression models. Between 1985 and 2008, there were 32,375
      breast cancer deaths in women in Colombia. Breast cancer mortality increased
      since 1985, although the annual increase varied between age groups and
      socioeconomic levels. Only in women aged 45-64 years old that live in areas of
      high socioeconomic levels, breast cancer mortality was stable or decreasing.
      Hence, successful cancer control is possible in middle income countries, as shown
      by the progress observed in certain groups. The development of an integrated
      strategy of early detection and early access to proper treatment, suitable for
      areas with limited resources, is an urgent necessity.

PMID- 22460616
TI  - Pathologic complete response after neoadjuvant therapy of breast cancer: pitfalls
      and shortcomings.

PMID- 22460617
TI  - Similar survival with single-agent capecitabine or taxane in first-line therapy
      for metastatic breast cancer.
AB  - Capecitabine is often offered as a first-line chemotherapy option for metastatic
      breast cancer (MBC). In this study, we compare characteristics of and survival
      among women prescribed first-line capecitabine or taxane monotherapy for MBC.
      Women receiving first-line chemotherapy for MBC from 1998 to 2005 were identified
      from the North Carolina tumor registry linked with Medicaid and Medicare claims
      records, and were followed through the end of 2005 with survival data from the
      National Death Index. T Tests and Chi-square tests were used to compare baseline
      characteristics. Overall survival and cancer-specific survival were examined
      using Cox proportional hazard modeling. There were 257 patients with MBC starting
      first-line chemotherapy with capecitabine (n=71) or a taxane (n=186). No
      differences in age, race, or Charlson comorbidity status were observed between
      groups. Hormone receptor negative tumors (31.0 vs. 17.7%, p=0.02) and patients
      insured by Medicaid (28 vs. 12%, p=0.002) were more prevalent in the capecitabine
      group. Time from metastasis to first-line chemotherapy was longer in the
      capecitabine group (52 vs. 26% began after 3 months, p<0.001). In multivariate
      analysis, treatment received was not associated with overall or cancer-specific
      survival. Among standard demographics, age was the only factor significantly
      associated with overall survival (HR 1.02, p=04). In this population-based study,
      women who received capecitabine as first-line treatment for MBC were more often
      hormone receptor negative and insured by Medicaid. In multivariate analysis,
      first-line capecitabine and taxane for MBC yielded similar overall and cancer
      specific survival outcomes.

PMID- 22460618
TI  - Recent developments in the treatment of cachexia: highlights from the 6th
      Cachexia Conference.

PMID- 22460619
TI  - The effect of age, sex, and physical activity on entheseal morphology in a
      contemporary Italian skeletal collection.
AB  - Entheseal changes are traditionally included in a large array of skeletal
      features commonly referred to as "skeletal markers of activity." However, medical
      studies and recent anthropological analyses of identified skeletal series suggest
      a complex combination of physiological and biomechanical factors underlying the
      variability of such "markers." The aim of this study is to examine the
      relationship between age, sex, physical activity, and entheseal variability. To
      this end, 23 postcranial entheses are examined in a large (N = 484) Italian
      contemporary skeletal series using standardized scoring methods. The sample
      comprises subjects of known age, sex and, mostly, occupation. Results show a
      strong relationship between age and entheseal changes. Differences between sexes
      are also highlighted, while the effects of physical activity appear moderate.
      Altogether, our study indicates that entheseal morphology primarily reflects the
      age of an individual, while correlation with lifetime activity remains ambiguous.

PMID- 22460620
TI  - A shorter time to the first treatment may be predicted by the absolute number of
      regulatory T-cells in patients with Rai stage 0 chronic lymphocytic leukemia.
AB  - Regulatory T-cells (Tregs) are increased in chronic lymphocytic leukemia(CLL) and
      correlates with clinical and biological features of active/progressive disease.
      However, little is known about their ability to predict the time to first
      treatment (TFT). We evaluated 75 patients with Rai stage 0 CLL, in whom the
      absolute number of Tregs was determined at diagnosis, and correlated to main
      clinical and biological features, as well as to the need of receiving any
      specific therapy during the course of the disease. After a median follow-up of 30
      months, 12 patients(16%) required therapy at some time from the diagnosis.
      Treated patients showed a significant higher number of peripheral white blood
      cells and B-lymphocytes, platelet count, cases with unmutated immunoglobulin
      heavy chain status, and high-risk cytogenetic abnormalities,as well as lower
      hemoglobin values, than patients who did not need therapy. A greater number of
      circulating Tregs was detected in treated patients (P < 0.001). Multivariate
      analysis confirmed that the absolute number of Tregs was an independent predictor
      of TFT in these patients, the best predictive cut-off being 41/mL. These data
      show that the absolute Tregs cell number is able to identify Rai stage 0 CLL
      patients at higher risk of requiring therapy.

PMID- 22460621
TI  - Conformation-specific spectroscopy of peptide fragment ions in a low-temperature
      ion trap.
AB  - We have applied conformer-selective infrared-ultraviolet (IR-UV) double-resonance
      photofragment spectroscopy at low temperatures in an ion trap mass spectrometer
      for the spectroscopic characterization of peptide fragment ions. We investigate b
      and a-type ions formed by collision-induced dissociation from protonated leucine
      enkephalin. The vibrational analysis and assignment are supported by nitrogen-15
      isotopic substitution of individual amino acid residues and assisted by density
      functional theory calculations. Under such conditions, b-type ions of different
      size are found to appear exclusively as linear oxazolone structures with
      protonation on the N-terminus, while a rearrangement reaction is confirmed for
      the a (4) ion in which the side chain of the C-terminal phenylalanine residue is
      transferred to the N-terminal side of the molecule. The vibrational spectra that
      we present here provide a particularly stringent test for theoretical approaches.

PMID- 22460622
TI  - Unique fragmentation of singly charged DEST cross-linked peptides.
AB  - It has previously been shown that when cross-linking reagent diethyl
      suberthioimidate (DEST) reacts with primary amines of proteins to yield
      amidinated residues, the primary amines retain their high basicity, and cross
      linked species can be enriched by strong cation exchange. It is now demonstrated
      that collisional activation of singly-charged DEST cross-linked peptide ions
      leads to preferential cleavage at the cross-linked sites. The resulting product
      ions facilitate the detection and identification of cross-linked peptides.

PMID- 22460623
TI  - Taste disorders after tonsillectomy: a long-term follow-up.
AB  - In a former study, taste disturbances after tonsillectomy seemed to be more
      frequent than expected. Eight percent of patients reported subjective taste
      disorders 6 months after tonsillectomy. Fifteen patients from the initial trial,
      who reported taste disorders after tonsillectomy, were contacted again for this
      long-term follow-up. A telephone interview using the same questionnaire
      addressing the current self-estimate of taste function was performed. At 32 +/-
      10 months following surgery, two (0.9%) patients still reported suffering from
      taste disturbance. This long-term follow-up study shows that dysgeusia following
      tonsillectomy occurs in approximately 1% of patients. These data should be
      considered when patients are informed about complications after tonsillectomy.

PMID- 22460624
TI  - Silver supramolecule catalyzed multicomponent reactions under mild conditions.
AB  - A novel supramolecular complex [Ag(L)(NO(3))] (1) was synthesized by reaction of
      the oxazoline-containing ligand 1,4-bis(4,5-dihydro-2-oxazolyl)benzene (L) with
      silver(I) nitrate and its structure was determined by single-crystal X-ray
      diffraction. Structurally speaking, the one-dimensional (1D) zigzag chains of 1,
      in which the Ag(I) is three-coordinated with distorted trigonal-planar
      coordination geometry, are linked together by the hydrogen bonding interactions
      to form a three-dimensional (3D) supramolecular structure. It was found that the
      silver supramolecule 1 catalyzes the three-component coupling reactions of
      aldehyde, alkyne, and amine in the air at room temperature to generate
      propargylic amines with high efficiency. No additional co-catalyst or activator
      is required. A variety of aldehydes and amines were used to demonstrate the
      versatility of the reaction.

PMID- 22460625
TI  - [The direct anterior approach to the hip revision].
AB  - OBJECTIVE: The objective of this paper is to describe a minimally invasive
      approach to revision total hip arthroplasty. INDICATIONS: Indications for
      revision hip arthroplasty are septic or aseptic loosening of one or both
      components of a hip arthroplasty. In revisions the direct anterior approach (DAA)
      allows for a small incision if only the cup has to be revised or in cases of stem
      revision; the femoral preparation can be performed strictly endofemorally from
      the proximal direction. The gluteal muscles can be preserved whether the approach
      is limited to the original interval between the musculus tensor fasciae latae and
      the rectus, or has to be extended. CONTRAINDICATIONS: If preservation of the
      gluteal muscles is desired, the DAA and its extension are the method of choice.
      For endofemoral revision other than detachment of the musculus tensor fasciae
      latae, hyperextension and adduction of the operated leg are important. If these
      cannot be achieved, an alternative operative strategy or a different approach
      should be considered. As this approach allows for extensions proximally and
      distally along the femur, it competes with lateral approaches to the hip joint
      and femur, and does not have additional specific contraindications. The
      availability of specific curved, angulated, or offset instruments is mandatory.
      SURGICAL TECHNIQUE: The starting point of the incision is found two
      fingerbreadths lateral and two finger breadths distal to the anterior superior
      iliac spine. The fascia of the musculus tensor fasciae latae is incised sharply
      at its midpoint. The interval is prepared strictly subfacially and medially to
      the musculus tensor fasciae latae to expose the hip joint. POSTOPERATIVE
      MANAGEMENT: For this approach we don't have any specific recommendations.
      Postoperative management depends mostly on the extension of the approach and the
      type of reconstruction performed. If the approach can be limited to the minimally
      invasive direct anterior portal, reduced muscle damage should result in faster
      rehabilitation. RESULTS: The retrospective analysis was performed on the data
      obtained from 48 revision operations with the minimally invasive direct anterior
      approach to total hip arthroplasty. The median cut-suture time was 108 min (42
      282 min); patients spent a median time of 10 days (4-33 days) in the hospital
      from the day of the operation. The most common revision operations were cup
      replacement with an augmentation ring (13 out of 48), stem revision (11 out of
      48), cup replacement (9 out of 48), H-TEP complete (3 out of 48), removing of
      ossifications (2 out of 48), cap revision (2 out of 48) and H-TEP removal with
      insertion of a spacer (2 out of 48). Complications attributed to the procedure
      were reported in 9 of the 48 cases: 1 wound-healing disorder, 1 late infection, 1
      hematoma, 1 deep vein thrombosis, 1 perforation (by the spacer) and 1
      ossification. Two patients were diagnosed with trochanteric pain syndrome. In one
      case an implant loosening was diagnosed 12 months after the revision.

PMID- 22460626
TI  - Joint analysis of binary and quantitative traits with data sharing and outcome
      dependent sampling.
AB  - We study the analysis of a joint association between a genetic marker with both
      binary (case-control) and quantitative (continuous) traits, where the
      quantitative trait values are only available for the cases due to data sharing
      and outcome-dependent sampling. Data sharing becomes common in genetic
      association studies, and the outcome-dependent sampling is the consequence of
      data sharing, under which a phenotype of interest is not measured for some
      subgroup. The trend test (or Pearson's test) and F-test are often, respectively,
      used to analyze the binary and quantitative traits. Because of the outcome
      dependent sampling, the usual F-test can be applied using the subgroup with the
      observed quantitative traits. We propose a modified F-test by also incorporating
      the genotype frequencies of the subgroup whose traits are not observed. Further,
      a combination of this modified F-test and Pearson's test is proposed by Fisher's
      combination of their P-values as a joint analysis. Because of the correlation of
      the two analyses, we propose to use a Gamma (scaled chi-squared) distribution to
      fit the asymptotic null distribution for the joint analysis. The proposed
      modified F-test and the joint analysis can also be applied to test single trait
      association (either binary or quantitative trait). Through simulations, we
      identify the situations under which the proposed tests are more powerful than the
      existing ones. Application to a real dataset of rheumatoid arthritis is
      presented.

PMID- 22460627
TI  - Does the A-not-B error in adult pet dogs indicate sensitivity to human
      communication?
AB  - Recent dog-infant comparisons have indicated that the experimenter's
      communicative signals in object hide-and-search tasks increase the probability of
      perseverative (A-not-B) errors in both species (Topal et al. 2009). These
      behaviourally similar results, however, might reflect different mechanisms in
      dogs and in children. Similar errors may occur if the motor response of
      retrieving the object during the A trials cannot be inhibited in the B trials or
      if the experimenter's movements and signals toward the A hiding place in the B
      trials ('sham-baiting') distract the dogs' attention. In order to test these
      hypotheses, we tested dogs similarly to Topal et al. (2009) but eliminated the
      motor search in the A trials and 'sham-baiting' in the B trials. We found that
      neither an inability to inhibit previously rewarded motor response nor
      insufficiencies in their working memory and/or attention skills can explain dogs'
      erroneous choices. Further, we replicated the finding that dogs have a strong
      tendency to commit the A-not-B error after ostensive-communicative hiding and
      demonstrated the crucial effect of socio-communicative cues as the A-not-B error
      diminishes when location B is ostensively enhanced. These findings further
      support the hypothesis that the dogs' A-not-B error may reflect a special
      sensitivity to human communicative cues. Such object-hiding and search tasks
      provide a typical case for how susceptibility to human social signals could
      (mis)lead domestic dogs.

PMID- 22460628
TI  - Cuttlefish rely on both polarized light and landmarks for orientation.
AB  - Cuttlefish are sensitive to linear polarization of light, a sensitivity that they
      use in predation and possibly in intraspecific communication. It has also been
      shown that cuttlefish are able to solve a maze using visual landmarks. In this
      study, cuttlefish were trained to solve a Y-maze with the e-vector of a polarized
      light and landmarks as redundant spatial information. The results showed that
      cuttlefish can use the e-vector orientation and landmarks in parallel to orient
      and that they are able to use either type of cue when the other one is missing.
      When they faced conflicting spatial information in the experimental apparatus,
      the majority of cuttlefish followed the e-vector rather than landmarks.
      Differences in response latencies in the different conditions of testing
      (training with both types of cue, tests with single cue or with conflicting
      information) were observed and discussed in terms of decision making. The ability
      to use near field and far field information may enable animals to interpret the
      partially occluded underwater light field.

PMID- 22460629
TI  - Domestication has not affected the understanding of means-end connections in
      dogs.
AB  - Recent studies have revealed that dogs often perform well in cognitive tasks in
      the social domain, but rather poorly in the physical domain. This dichotomy has
      led to the hypothesis that the domestication process might have enhanced the
      social cognitive skills of dogs (Hare et al. in Science 298:1634-1636, 2002;
      Miklosi et al. in Curr Biol 13:763-766, 2003) but at the same time had a
      detrimental effect on their physical cognition (Frank in Z Tierpsychol 5:389-399,
      1980). Despite the recent interest in dog cognition and especially the effects of
      domestication, the latter hypothesis has hardly been tested and we lack detailed
      knowledge of the physical understanding of wolves in comparison with dogs. Here,
      we set out to examine whether adult wolves and dogs rely on means-end connections
      using the string-pulling task, to test the prediction that wolves would perform
      better than dogs in such a task of physical cognition. We found that at the group
      level, dogs were more prone to commit the proximity error, while the wolves
      showed a stronger side bias. Neither wolves nor dogs showed an instantaneous
      understanding of means-end connection, but made different mistakes. Thus, the
      performance of the wolves and dogs in this string-pulling task did not confirm
      that domestication has affected the physical cognition of dogs.

PMID- 22460630
TI  - Threat perception in the chameleon (Chamaeleo chameleon): evidence for
      lateralized eye use.
AB  - Chameleons are arboreal lizards with highly independent, large amplitude eye
      movements. In response to an approaching threat, a chameleon on a vertical pole
      moves so as to keep itself away from the threat. In so doing, it shifts between
      monocular and binocular scanning of the threat and of the environment. We
      analyzed eye movements in the Common chameleon, Chamaeleo chameleon, during
      avoidance response for lateralization, that is, asymmetry at the
      functional/behavioral levels. The chameleons were exposed to a threat,
      approaching horizontally from clockwise or anti-clockwise directions, and that
      could be viewed monocularly or binocularly. Our results show three broad patterns
      of eye use, as determined by durations spent viewing the threat and by frequency
      of eye shifts. Under binocular viewing, two of the patterns were found to be both
      side dependent, that is, lateralized and role dependent ("leading" or
      "following"). However, under monocular viewing, no such lateralization was
      detected. We discuss these findings in light of the situation not uncommon in
      vertebrates, of independent eye movements and a high degree of optic nerve
      decussation and that lateralization may well occur in organisms that are
      regularly exposed to critical stimuli from all spatial directions. We point to
      the need of further investigating lateralization at fine behavioral levels.

PMID- 22460631
TI  - Toward the non-surgical management of locally advanced rectal cancer.
AB  - Neoadjuvant short-course radiotherapy and long-course chemoradiation (CRT) reduce
      local recurrence rates when compared to surgery alone and remain widely accepted
      as standard of care for patients with locally advanced rectal cancer. However,
      surgery is not without complications and a non-surgical approach in carefully
      selected patients warrants evaluation. A pathological complete response to CRT is
      associated with a significant improvement in survival and it has been suggested
      that a longer time interval between the completion of CRT and surgery increases
      tumor downstaging. Intensification of neoadjuvant treatment regimens to increase
      tumor downstaging has been evaluated in a number of clinical trials and more
      recently the introduction of neoadjuvant chemotherapy prior to CRT has
      demonstrated high rates of radiological tumor regression. Careful selection of
      patients using high-resolution MRI may allow a non-surgical approach in a
      subgroup of patients achieving a complete response to neoadjuvant therapies after
      an adequate time period. Clearly this needs prospective evaluation within a
      clinical trial setting, incorporating modern imaging techniques, and tissue
      biomarkers to allow accurate prediction and assessment of response.

PMID- 22460633
TI  - The role of serum proteins in sepsis.

PMID- 22460632
TI  - Tempol protects against intravitreous indocyanine green-induced retinal damage in
      rats.
AB  - PURPOSE: Indocyanine green (ICG) has been widely used as a vital dye for macular
      surgery. However, ICG can be toxic to retinal cells. Here we evaluate whether
      tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a free radical
      scavenger, can protect against ICG-induced retinal damage in rats. METHODS: Brown
      Norway rats received intravitreal injections of ICG 0.5 % or BSS as controls.
      Tempol (20 mg/kg BW) or PBS as a control was administered intraperitoneally 24 h
      and 30 min before ICG and once daily for 7 consecutive days. Tempol was detected
      in the retina using electron paramagnetic resonance (EPR) spectroscopy. One week
      after ICG injections, the effects of tempol on retinal toxicity were assessed by
      retinal ganglion cell (RGC) back-labeling and by light microscopy.
      Electroretinography (ERG) was performed after 1 and 2 weeks. RESULTS: ICG
      administration reduced RGC numbers by 17 % (1,943 +/- 45 vs. 2,342 +/- 31
      RGCs/mm(2)). Tempol treatment rescued RGCs in a significant manner (2,258 +/- 36,
      p < 0.01) and diminished morphological changes detected by light microscopy. ICG
      injected eyes showed a significant reduction of ERG potentials only in PBS
      treated animals (V(max) 530 +/- 145 uV vs. 779 +/- 179 uV, p = 0.0052), but not
      in the tempol-treated group. CONCLUSIONS: Tempol significantly attenuates ICG
      induced toxicity in rat retinas and may therefore be considered for further
      evaluation as accompanying treatment in ICG-assisted chromovitrectomy.

PMID- 22460634
TI  - The blood-brain barrier and pathogens: Hadrian's Wall or a Dardanian gate?

PMID- 22460635
TI  - Blood-brain barrier and retroviral infections.
AB  - Homeostasis in the central nervous system (CNS) is maintained by active
      interfaces between the bloodstream and the brain parenchyma. The blood-brain
      barrier (BBB) constitutes a selective filter for exchange of water, solutes,
      nutrients, and controls toxic compounds or pathogens entry. Some parasites,
      bacteria, and viruses have however developed various CNS invasion strategies, and
      can bypass the brain barriers. Concerning viruses, these strategies include
      transport along neural pathways, transcytosis, infection of the brain endothelial
      cells, breaching of the BBB, and passage of infected-leukocytes. Moreover,
      neurotropic viruses can alter BBB functions, thus compromising CNS homeostasis.
      Retroviruses have been associated to human neurological diseases: HIV (human
      immunodeficiency virus 1) can induce HIV-associated dementia, and HTLV-1 (human T
      lymphotropic virus 1) is the etiological factor of tropical spastic
      paraparesis/HTLV-1 associated myelopathy (TSP/HAM). The present review focuses on
      how the different retroviruses interact with this structure, bypass it and alter
      its functions.

PMID- 22460636
TI  - Targeting of the central nervous system by Listeria monocytogenes.
AB  - Among bacteria that reach the central nervous system (CNS), Listeria
      monocytogenes (Lm) is one of deadliest, in human and ruminant. This facultative
      intracellular bacterium has the particularity to induce meningitis,
      meningoencephalitis and rhombencephalitis. Mechanisms by which Lm accesses the
      CNS remain poorly understood, but two major routes of infection have been
      proposed, based on clinical, in vitro and in vivo observations. A retrograde
      neural route is likely to occur in ruminants upon crossing of the oral
      epithelium, and this probably accounts for the observation that Lm induces almost
      exclusively rhombencephalitis in these animals. In contrast, the hematogenous
      route is likely the most frequent in human, in whom bacteria circulating in the
      blood, either free or associated with leukocytes are thought to breach the blood
      brain barrier. New animal models that faithfully reproduce the hallmarks of human
      neurolisterisosis will allow addressing the molecular mechanisms underlying Lm
      ability to induce CNS disease, and improve our understanding of the
      pathophysiology of this deadly infection.

PMID- 22460638
TI  - Acidic pH: enemy or ally for enteric bacteria?
AB  - The first stress that foodborne pathogens find upon ingestion is the very acidic
      pH of the stomach of the host. In addition, intracellular pathogens like
      Salmonella are submitted to low pH inside the host cells. Two general acid
      survival systems are found in these organisms: acid resistance mechanisms and
      acid tolerance responses. These mechanisms involve the synthesis of a series of
      acid shock proteins. Only a subset of these proteins is directly involved in acid
      survival. This is related to the fact that low pH is not only a stress to cope
      with, but it is also an important signal that indicates to the bacterium that it
      is in a potential host environment and that triggers the induction of many
      virulence genes. Asr is an acid shock protein that supports growth of Escherichia
      coli at moderate acidity. In this issue of Virulence, Allam et al. investigate
      the role of STM1485, the homologous of asr in Salmonella enterica serovar
      Typhimurium, in acid survival and virulence. Although STM1485 is not required for
      acid survival of S. enterica, it is necessary for intracellular replication in
      human epithelial cells and murine macrophages, and to prevent the progression of
      the Salmonella-containing vacuole along the degradative pathway. In addition,
      Allam et al. are able to show that the defects of the STM1485 mutant at the
      cellular level correlate with reduced virulence in the mouse model.

PMID- 22460637
TI  - Protein kinase A and fungal virulence: a sinister side to a conserved nutrient
      sensing pathway.
AB  - Diverse fungal species are the cause of devastating agricultural and human
      diseases. As successful pathogenesis is dependent upon the ability of the fungus
      to adapt to the nutritional and chemical environment of the host, the
      understanding of signaling pathways required for such adaptation will provide
      insights into the virulence of these pathogens and the potential identification
      of novel targets for antifungal intervention. The cAMP-PKA signaling pathway is
      well conserved across eukaryotes. In the nonpathogenic yeast, S. cerevisiae, PKA
      is activated in response to extracellular nutrients and subsequently regulates
      metabolism and growth. Importantly, this pathway is also a regulator of
      pathogenesis, as defects in PKA signaling lead to an attenuation of virulence in
      diverse plant and human pathogenic fungi. This review will compare and contrast
      PKA signaling in S. cerevisiae vs. various pathogenic species and provide a
      framework for the role of this pathway in regulating fungal virulence.

PMID- 22460640
TI  - Identification of small, noncoding RNAs in pathogenic Yersinia species:
      implications for evolution and virulence.

PMID- 22460641
TI  - On the effect of the path length of small-world networks on epidemic dynamics.
AB  - We show how one can trace in a systematic way the coarse-grained solutions of
      individual-based stochastic epidemic models evolving on heterogeneous complex
      networks with respect to their topological characteristics. In particular, we
      illustrate the "distinct" impact of the average path length (with respect to the
      degree and clustering distributions) on the emergent behavior of detailed
      epidemic models; to achieve this we have developed an algorithm that allows its
      tuning at will. The framework could be used to shed more light on the influence
      of weak social links on epidemic spread within small-world network structures,
      and ultimately to provide novel systematic computational modeling and exploration
      of better contagion control strategies.

PMID- 22460639
TI  - Passage of parasites across the blood-brain barrier.
AB  - The blood-brain barrier (BBB) is a structural and functional barrier that
      protects the central nervous system (CNS) from invasion by blood-borne pathogens
      including parasites. However, some intracellular and extracellular parasites can
      traverse the BBB during the course of infection and cause neurological
      disturbances and/or damage which are at times fatal. The means by which parasites
      cross the BBB and how the immune system controls the parasites within the brain
      are still unclear. In this review we present the current understanding of the
      processes utilized by two human neuropathogenic parasites, Trypanosoma brucei spp
      and Toxoplasma gondii, to go across the BBB and consequences of CNS invasion. We
      also describe briefly other parasites that can invade the brain and how they
      interact with or circumvent the BBB. The roles played by parasite-derived and
      host-derived molecules during parasitic and white blood cell invasion of the
      brain are discussed.

PMID- 22460642
TI  - Serum proteins modulate lipopolysaccharide and lipoteichoic acid-induced
      activation and contribute to the clinical outcome of sepsis.
AB  - Bacterial cell wall components, such LPS and LTA, are potent initiators of an
      inflammatory response that can lead to septic shock. The advances in the past
      were centered around membrane-bound receptors and intracellular events, but our
      understanding of the initial interactions of these bacterial components with
      serum proteins as they enter the bloodstream remain unclear. In this study we
      identified several serum proteins, which are involved in the innate recognition
      of bacterial products. Using affinity chromatography and mass spectrometry we
      performed proteomic analysis of LPS- and LTA-binding serum proteins. We isolated
      proteins from normal serum that can interact with LPS and LTA. Fluorescent
      binding experiments and cytokine assays revealed that serum proteins, such as
      apolipoprotein, LDL, transferrin and holotransferrin could neutralize LPS/LTA
      binding as well as the subsequent inflammatory response, suggesting that serum
      proteins modulate LPS/LTA-induced responses. When compared with the proteomic
      profile of serum from septic patients it was shown that these proteins were in
      lower abundance. Investigation of serum proteins in 25 critically ill patients
      with a mortality rate of 40% showed statistically higher levels of these proteins
      in survivors. Patients surviving sepsis had statistically significant higher
      levels of apolipoprotein, albumin, LDL, transferrin and holotransferrin than
      individuals that succumbed, suggesting that these proteins have an inhibitory
      effect on LPS/LTA-induced inflammatory responses and in their absence there might
      be an augmented inflammatory response in sepsis.

PMID- 22460643
TI  - Acidic pH induced STM1485 gene is essential for intracellular replication of
      Salmonella.
AB  - During the course of infection, Salmonella has to face several potentially lethal
      environmental conditions, one such being acidic pH. The ability to sense and
      respond to the acidic pH is crucial for the survival and replication of
      Salmonella. The physiological role of one gene (STM1485) involved in this
      response, which is upregulated inside the host cells (by 90- to 113-fold) is
      functionally characterized in Salmonella pathogenesis. In vitro, the DeltaSTM1485
      neither exhibited any growth defect at pH 4.5 nor any difference in the acid
      tolerance response. The DeltaSTM1485 was compromised in its capacity to
      proliferate inside the host cells and complementation with STM1485 gene restored
      its virulence. We further demonstrate that the surface translocation of
      Salmonella pathogenicity island-2 (SPI-2) encoded translocon proteins, SseB and
      SseD were reduced in the DeltaSTM1485. The increase in co-localization of this
      mutant with lysosomes was also observed. In addition, the DeltaSTM1485 displayed
      significantly reduced competitive indices (CI) in spleen, liver and mesenteric
      lymph nodes in murine typhoid model when infected by intra-gastric route. Based
      on these results, we conclude that the acidic pH induced STM1485 gene is
      essential for intracellular replication of Salmonella.

PMID- 22460644
TI  - Cerebral malaria: mysteries at the blood-brain barrier.
AB  - Cerebral malaria is the most severe pathology caused by the malaria parasite,
      Plasmodium falciparum. The pathogenic mechanisms leading to cerebral malaria are
      still poorly defined as studies have been hampered by limited accessibility to
      human tissues. Nevertheless, histopathology of post-mortem human tissues and
      mouse models of cerebral malaria have indicated involvement of the blood-brain
      barrier in cerebral malaria. In contrast to viruses and bacteria, malaria
      parasites do not infiltrate and infect the brain parenchyma. Instead, rupture of
      the blood-brain barrier occurs and may lead to hemorrhages resulting in
      neurological alterations. Here, we review the most recent findings from human
      studies and mouse models on the interactions of malaria parasites and the blood
      brain barrier, shedding light on the pathogenesis of cerebral malaria, which may
      provide directions for possible interventions.

PMID- 22460645
TI  - Toxoplasma gondii and the blood-brain barrier.
AB  - Infection with the protozoan parasite Toxoplasma gondii is characterized by
      asymptomatic latent infection in the central nervous system and skeletal muscle
      tissue in the majority of immunocompentent individuals. Life-threatening
      reactivation of the infection in immunocompromized patients originates from
      rupture of Toxoplasma cysts in the brain. While major progress has been made in
      our understanding of the immunopathogenesis of infection the mechanism(s) of
      neuroinvasion of the parasite remains poorly understood. The present review
      presents the current understanding of blood-brain barrier (patho)physiology and
      the interaction of Toxoplasma gondii with cells of the blood-brain barrier.

PMID- 22460648
TI  - One-step solvothermal synthesis of Fe3O4@C core-shell nanoparticles with tunable
      sizes.
AB  - We report the synthesis of Fe3O4@C core-shell nanoparticles (FCNPs) by using a
      facile one-step solvothermal method. The FCNPs consisted of Fe3O4 particles as
      the cores and amorphous uniform carbon shells. The content of Fe3O4 is up to 81.6
      wt%. These core-shell nanoparticles are aggregated by primary nanocrystals with a
      size of 10-12 nm. The FCNPs possess a hollow interior, high magnetization,
      excellent absorption properties and abundant surface hydroxyl groups. A possible
      growth mechanism of the FCNPs is proposed. The role of glucose in regulating the
      grain size and morphology of the particles is discussed. The absorption
      properties of the FCNPs towards Cr(VI) in aqueous solution is investigated. We
      demonstrate that the FCNPs can effectively remove more than 90 wt% of Cr(VI) from
      aqueous solution.

PMID- 22460647
TI  - Characterization of tannase protein sequences of bacteria and fungi: an in silico
      study.
AB  - The tannase protein sequences of 149 bacteria and 36 fungi were retrieved from
      NCBI database. Among them only 77 bacterial and 31 fungal tannase sequences were
      taken which have different amino acid compositions. These sequences were analysed
      for different physical and chemical properties, superfamily search, multiple
      sequence alignment, phylogenetic tree construction and motif finding to find out
      the functional motif and the evolutionary relationship among them. The
      superfamily search for these tannase exposed the occurrence of proline
      iminopeptidase-like, biotin biosynthesis protein BioH, O-acetyltransferase,
      carboxylesterase/thioesterase 1, carbon-carbon bond hydrolase, haloperoxidase,
      prolyl oligopeptidase, C-terminal domain and mycobacterial antigens families and
      alpha/beta hydrolase superfamily. Some bacterial and fungal sequence showed
      similarity with different families individually. The multiple sequence alignment
      of these tannase protein sequences showed conserved regions at different
      stretches with maximum homology from amino acid residues 389-469 and 482-523
      which could be used for designing degenerate primers or probes specific for
      tannase producing bacterial and fungal species. Phylogenetic tree showed two
      different clusters; one has only bacteria and another have both fungi and
      bacteria showing some relationship between these different genera. Although in
      second cluster near about all fungal species were found together in a corner
      which indicates the sequence level similarity among fungal genera. The
      distributions of fourteen motifs analysis revealed Motif 1 with a signature amino
      acid sequence of 29 amino acids, i.e. GCSTGGREALKQAQRWPHDYDGIIANNPA, was
      uniformly observed in 83.3 % of studied tannase sequences representing its
      participation with the structure and enzymatic function.

PMID- 22460646
TI  - Molecular mechanisms of cryptococcal meningitis.
AB  - Fungal meningitis is a serious disease caused by a fungal infection of the
      central nervous system (CNS) mostly in individuals with immune system
      deficiencies. Fungal meningitis is often fatal without proper treatment, and the
      mortality rate remains unacceptably high even with antifungal drug interventions.
      Currently, cryptococcal meningitis is the most common fungal meningitis in HIV
      1/AIDS, and its disease mechanism has been extensively studied. The key steps for
      fungi to infect brain and cause meningitis after establishment of local infection
      are the dissemination of fungal cells to the bloodstream and invasion through the
      blood brain barrier to reach the CNS. In this review, we use cryptococcal CNS
      infection as an example to describe the current molecular understanding of fungal
      meningitis, including the establishment of the infection, dissemination, and
      brain invasion. Host and microbial factors that contribute to these infection
      steps are also discussed.

PMID- 22460652
TI  - A possible mechanism of renal cell death after ischemia/reperfusion.
AB  - Linkermann et al. provide the first evidence for a possible biochemical mechanism
      of necrotic kidney cell death associated with renal ischemia/reperfusion-induced
      acute kidney injury. The mechanisms of several pathways resulting in programmed
      necrosis were recently elucidated and rely on receptor-interacting protein
      kinases 1 and 3. Using an inhibitor of one of these kinases, Linkermann et al.
      were able to ameliorate functional and morphologic kidney damage after
      ischemia/reperfusion.

PMID- 22460653
TI  - ADMA and NOS regulation in chronic renal disease: beyond the old rivalry for l
      arginine.
AB  - Chronic kidney disease is associated with increased levels of assymetric
      N(G),N(G)-dimethylarginine (ADMA), which is predictive of increased mortality and
      cardiovascular disease. ADMA induces endothelial dysfunction through competitive
      inhibition of the endothelial nitric oxide (eNOS) substrate L-arginine. Kajimoto
      et al. show that ADMA may also reduce nitric oxide production via decreased eNOS
      phosphorylation; this effect is mediated by the MAPK pathway and can be reversed
      in vivo by increased catabolism of ADMA through dimethylarginine
      dimethylaminohydrolase-1 overexpression.

PMID- 22460654
TI  - From basic anatomic configuration to maturation success.
AB  - The arteriovenous fistula is the preferred vascular access for hemodialysis
      patients because of its low complication rate and lower costs, but it still has
      unacceptable failure rates. Krishnamoorthy et al. implicate the geometry of the
      fistula in the temporal and spatial variations occurring in two of the most
      important parameters of fistula maturation, blood flow and vessel diameter.

PMID- 22460656
TI  - Ethnic factors of the glomerular filtration rate estimating equation.

PMID- 22460657
TI  - The hypothesis that type of species change depends on neutral-pH PD solutions.

PMID- 22460659
TI  - Large urate cystolith associated with Proteus urinary tract infection.

PMID- 22460660
TI  - Nephrology crossword: dyskalemias.

PMID- 22460661
TI  - Scurvy in the Great Irish Famine: evidence of vitamin C deficiency from a mid
      19th century skeletal population.
AB  - Scurvy has increasingly been recognized in archaeological populations since the
      1980s but this study represents the first examination of the paleopathological
      findings of scurvy in a known famine population. The Great Famine (1845-1852) was
      a watershed in Irish history and resulted in the death of one million people and
      the mass emigration of just as many. It was initiated by a blight which
      completely wiped out the potato-virtually the only source of food for the poor of
      Ireland. This led to mass starvation and a widespread occurrence of infectious
      and metabolic diseases. A recent discovery of 970 human skeletons from mass
      burials dating to the height of the famine in Kilkenny City (1847-1851) provided
      an opportunity to study the skeletal manifestations of scurvy-a disease that
      became widespread at this time due to the sudden lack of Vitamin C which had
      previously almost exclusively been provided by the potato. A three-scale
      diagnostic reliance approach has been employed as a statistical aid for
      diagnosing the disease in the population. A biocultural approach was adopted to
      enable the findings to be contextualized and the etiology and impact of the
      disease explored. The results indicate that scurvy indirectly influenced famine
      induced mortality. A sex and stature bias is evident among adults in which males
      and taller individuals displayed statistically significantly higher levels of
      scorbutic lesions. The findings have also suggested that new bone formation at
      the foramen rotundum is a diagnostic criterion for the paleopathological
      identification of scurvy, particularly among juveniles.

PMID- 22460663
TI  - Diffusion tensor imaging in anxiety disorders.
AB  - Diffusion tensor imaging (DTI) can be used to examine the structural integrity of
      regional white matter and to map white matter tracts. DTI studies have been
      performed in several psychiatric disorders, especially in those for which a
      developmental or a neuropsychiatric component was postulated. Thus far, the use
      of DTI has been very limited in panic disorder, social anxiety disorder, and
      generalized anxiety disorder, and somewhat more extensive in post-traumatic
      stress disorder and obsessive-compulsive disorder. In most anxiety disorders, the
      results of DTI studies are in line with other structural and functional MRI
      findings and can be interpreted within the frameworks of existing models for the
      neurocircuitry of the various disorders. DTI findings could further enrich
      neurobiological models for anxiety disorders, although replication is often
      warranted, and studies in pediatric populations are lagging behind remarkably.

PMID- 22460662
TI  - Population-based screening for anemia using first-time blood donors.
AB  - Anemia is an important public health concern. Data from population-based surveys
      such as the National Health and Nutrition Examination Survey (NHANES) are the
      gold standard, but are obtained infrequently and include only small samples from
      certain minority groups. We assessed whether readily available databases of blood
      donor hemoglobin values could be used as a surrogate for population hemoglobin
      values from NHANES. Blood donor venous and fingerstick hemoglobin values were
      compared to 10,254 NHANES 2005-2008 venous hemoglobin values using
      demographically stratified analyses and ANOVA. Fingerstick hemoglobins or
      hematocrits were converted to venous hemoglobin estimates using regression
      analysis. Venous hemoglobin values from 1,609 first time donors correlated
      extremely well with NHANES data across different ages, genders, and demographic
      groups. Cigarette smoking increased hemoglobin by 0.26-0.59 g/dL depending on the
      intensity. Converted fingerstick hemoglobin from 36,793 first time donors agreed
      well with NHANES hemoglobin (weighted mean hemoglobin of 15.53 g/dL for donors
      and 15.73 g/dL for NHANES) with similar variation in mean hemoglobin by age.
      However, compared to NHANES, the larger donor data set showed reduced differences
      in mean hemoglobin between Blacks and other races/ethnicities. Overall, first
      time donor fingerstick hemoglobins approximate US population data and represent a
      readily available public health resource for ongoing anemia surveillance.

PMID- 22460664
TI  - Minimally invasive options for salivary calculi.
AB  - The aim of this study was to review the advantages, limitations, and
      international interdisciplinary expert perspectives and contrasts of salivary
      gland endoscopy and transoral techniques in the diagnosis and management of
      salivary gland calculi and their adaptation in North America. The transition from
      transcervical approaches to strictly sialendoscopic approaches is a broad chasm
      and often not feasible. Sialendoscopy, sialendoscopy-assisted, intraoral, and
      transcervical approaches all have surgical value. Diagnostic sialendoscopy,
      interventional sialendoscopy, sialendoscopy-assisted, and transoral techniques
      have been a major step forward, not only in providing an accurate means of
      diagnosing and locating intraductal obstructions, but also in permitting
      minimally invasive surgical treatment that can successfully manage blockages
      precluding sialoadenectomy in most cases. A flexible methodology is required.
      Multiple or combined measured may prove effective.

PMID- 22460665
TI  - Dynamics of circulating progesterone concentrations before and during luteolysis:
      a comparison between cattle and horses.
AB  - The profile of circulating progesterone concentration is more dynamic in cattle
      than in horses. Greater prominence of progesterone fluctuations in cattle than in
      horses reflect periodic interplay in cattle between pulses of a luteotropin
      (luteinizing hormone; LH) and pulses of a luteolysin (prostaglandin F2alpha;
      PGF2alpha). A dose of PGF2alpha that induces complete regression of a mature
      corpus luteum with a single treatment in cattle or horses is an overdose. The
      overdose effects on the progesterone profile in cattle are an immediate
      nonphysiological increase taking place over about 30 min, a decrease to below the
      original concentration, a dose-dependent rebound 2 h after treatment, and a
      progressive decrease until the end of luteolysis. An overdose of PGF2alpha in
      horses results in a similar nonphysiological increase in progesterone followed by
      complete luteolysis; a rebound does not occur. An overdose of PGF2alpha and
      apparent lack of awareness of the rebound phenomenon has led to faulty
      interpretations on the nature of spontaneous luteolysis. A transient progesterone
      suppression and a transient rebound occur within the hours of a natural PGF2alpha
      pulse in cattle but not in horses. Progesterone rebounds are from the combined
      effects of an LH pulse and the descending portion of a PGF2alpha pulse. A
      complete transitional progesterone rebound occurs at the end of preluteolysis and
      the beginning of luteolysis and returns progesterone to its original
      concentration. It is proposed that luteolysis does not begin in cattle until
      after the transitional rebound. During luteolysis, rebounds are incomplete and
      gradually wane. A partial rebound during luteolysis in cattle is associated with
      a concomitant increase in luteal blood flow. A similar increase in luteal blood
      flow does not occur in mares.

PMID- 22460666
TI  - Production of donor-derived offspring by allogeneic transplantation of
      spermatogonia in the yellowtail (Seriola quinqueradiata).
AB  - Although the yellowtail (Seriola quinqueradiata) is the fish most commonly farmed
      in Japan, breeding of this species has not yet started. This is primarily due to
      the lack of sufficiently sophisticated methods for manipulating gametogenesis,
      which makes it difficult to collect gametes from specific dams and sires. If it
      were possible to produce large numbers of surrogate fish by transplanting germ
      cells isolated from donor individuals harboring desirable genetic traits, then
      the probability of acquiring gametes carrying the donor-derived haplotype would
      increase, and breeding programs involving this species might increase as a
      result. As a first step, we established a method for the allogeneic
      transplantation of yellowtail spermatogonia and the production of donor-derived
      offspring. Donor cells were collected from immature (10-month-old) yellowtail
      males with testes containing abundant type A spermatogonia, labeled with PKH26
      fluorescent dye, and transferred into the peritoneal cavities of 8-day-old
      larvae. Fluorescence observation at 28 days post-transplantation revealed that
      PKH26-labeled cells were incorporated into recipients' gonads. To assess whether
      donor-derived spermatogonia could differentiate into functional gametes in the
      allogeneic recipient gonads, gametes collected from nine male and four female
      adult recipients were fertilized with wild-type eggs and milt. Analysis of
      microsatellite DNA markers confirmed that some of the first filial (F(1))
      offspring were derived from donor fish, with the average contribution of donor
      derived F(1) offspring being 66% and the maximum reaching 99%. These findings
      confirmed that our method was effective for transplanting yellowtail
      spermatogonia into allogeneic larvae to produce donor-derived offspring.

PMID- 22460668
TI  - Hedgehog signaling in follicle development.

PMID- 22460667
TI  - Ovarian FAM110C (family with sequence similarity 110C): induction during the
      periovulatory period and regulation of granulosa cell cycle kinetics in rats.
AB  - FAM110C belongs to a family of proteins that regulates cell proliferation. In the
      present study, the spatiotemporal expression pattern of FAM110C and its potential
      role were examined during the periovulatory period. Immature female rats were
      injected with equine chorionic gonadotropin (eCG) followed by human chorionic
      gonadotropin (hCG) and ovaries or granulosa cells were collected at various times
      after hCG administration (n = 3/time point). Expression levels of Fam110c mRNA
      and protein were highly induced both in intact ovaries and granulosa cells at 8
      to 12 h after hCG treatment. In situ hybridization analysis demonstrated Fam110c
      mRNA expression was induced in theca and granulosa cells at 4 h after hCG,
      primarily localized to granulosa cells at 8 h and 12 h, and decreased at 24 h
      after hCG. There was negligible Fam110c mRNA detected in newly forming corpora
      lutea. In rat granulosa cell cultures, hCG induced expression of Fam110c mRNA was
      inhibited by RU486, whereas NS398 and AG1478 had no effect, suggesting that
      Fam110c expression is regulated in part by the progesterone receptor pathway.
      Promoter activity analysis revealed that an Sp1 site was important for the
      induction of Fam110c expression by hCG. Overexpression of FAM110C promoted
      granulosa cells to arrest at the G(1) phase of the cell cycle but did not change
      progesterone levels. In summary, hCG induces Fam110c mRNA expression in granulosa
      cells by activation of an Sp1-binding site and the actions of progesterone. Our
      findings suggest that FAM110C may control granulosa cell differentiation into
      luteal cells by arresting cell cycle progression.

PMID- 22460669
TI  - Gender differences in benign essential blepharospasm.
AB  - PURPOSE: Detection of differences in disease characteristics between male and
      female patients with benign essential blepharospasm (BEB). METHODS: We
      retrospectively reviewed charts of 32 male and 61 female BEB patients, comparing
      the time interval between treatments with botulinum toxin A. We prospectively
      compared BEB-related questionnaire results between 36 female and 15 male
      patients. RESULTS: The mean interval between treatment in weeks was 16.69 for men
      and 17.31 for women (p = 0.19). The questionnaire results showed a higher degree
      of symptom severity and frequency in women over men. (p = 0.008), but similar
      responses for disease-related handicap in daily activities. CONCLUSIONS: Aside
      from greater symptom severity and frequency among women, we found no significant
      differences between male and female patients with BEB.

PMID- 22460670
TI  - Cosmetic comparison of gold weight and platinum chain insertion in primary upper
      eyelid loading for lagophthalmos.
AB  - PURPOSE: Platinum chains are thinner than gold weights (GWs) and may confer a
      better eyelid curvature profile with reduced visibility. Outcomes compared eyelid
      measurements, cosmesis, and complications. METHODS: Forty-two primary GW and 17
      primary platinum chain insertions were identified and subsequently matched for
      laterality, pathology, and weight of implant. Twenty-two patients were randomly
      allocated into 2 groups for comparison; those receiving a GW (n = 11) or platinum
      chain (n = 11) to formulate a retrospective case-controlled study. Primary upper
      eyelid loading surgery with both implants involved a standard technique of a high
      tarsal placement with levator recession. Blinded assessment of preoperative and 6
      month postoperative photographs calculated eyelid parameters: upper marginal
      reflex distance and lagophthalmos. Standardized photographs were used to define
      cosmesis in terms of abnormal eyelid contour and prominence. RESULTS: Gold
      weights demonstrated an improvement in eyelid parameters. Nine eyelids had
      prominent implants: mild (2), moderate (3), and severe (4). Eyelid contour was
      affected in 7 patients, 5 with droop, and 2 with flattened contour. Platinum
      chain improved eyelid measurements. Mild eyelid prominence was noted in 2 cases,
      but eyelid contour remained normal in all patients. No complications were noted
      with either the GW or the platinum chain implants. CONCLUSION: Both devices are
      successful in treating complications of lagophthalmos. Platinum chains appear
      less prominent and maintain normal eyelid contour. Although more expensive,
      platinum chains appear to be as safe and effective as GWs yet provide better
      cosmesis.

PMID- 22460671
TI  - Recurrent orbital paraganglioma:  a clinicopathological correlation of an
      extremely rare tumor.
AB  - Orbital paraganglioma is an extremely rare clinical entity with fewer than 40
      cases reported in the literature. A well-documented case of a recurrent orbital
      paraganglioma is reported and its clinical, radiologic, histopathologic, and
      immunohistochemical features are discussed.

PMID- 22460672
TI  - Comparison of surgical outcomes of large orbital fractures reconstructed with
      porous polyethylene channel and porous polyethylene titan barrier implants.
AB  - PURPOSE: To compare the postoperative outcomes of large orbital fractures
      repaired with porous polyethylene (PP) channel implants (PPCIs) and PP titan
      barrier implants (PPTBs). METHODS: Medical records of 42 patients who underwent
      surgical reconstruction for a large orbital fracture with either PPCI or PPTB
      were reviewed retrospectively. The degree of diplopia, determined with a
      binocular single vision test, and enophthalmos, measured by a Hertel
      exophthalmometer, was compared between 2 implant groups. Orbital volumes were
      calculated using CT scans and the measuring tool. RESULTS: Of the 42 patients
      examined, 16 received PPCI and 26 received PPTB. No significant difference in the
      degree of diplopia was observed between the 2 implant groups before surgery, and
      1 and 3 months after surgery (p = 0.256, 0.408, and 0.432, respectively).
      Preoperative average enophthalmos measuring 1.28 mm and 1.04 mm was successfully
      corrected to 0.19 mm and 0.25 mm 3 months after reconstruction with PPCI and
      PPTB, respectively. The fractured orbit volumes and nonfractured contralateral
      orbit volumes were 24.96 +/- 2.32 cm3 and 23.18 +/- 1.733 cm in the PPCI group,
      and 26.80 +/- 2.10 cm3 and 24.13 +/- 2.28 cm3 in the PPTB group, respectively.
      After surgery, the fractured orbit volumes significantly decreased to 23.39 +/-
      2.82 cm3 in the PPCI group and to 23.53 +/- 1.74 cm3 in the PPTB group; these
      values were not significantly different from that of the nonfractured orbit (p =
      0.681 for PPCI and 0.204 for PPTB). CONCLUSIONS: Porous polyethylene channel
      implant and PPTB are both effective implant materials for the repair of large
      orbital fractures; however, PPTB has the additional benefit of not requiring
      screw fixation.

PMID- 22460673
TI  - Topical 5-fluorouracil for the treatment of periocular actinic keratosis and low
      grade squamous malignancy.
AB  - PURPOSE: To evaluate the efficacy and safety of topical 5% fluorouracil (5-FU)
      cream in the treatment of periocular actinic keratosis and squamous cell
      carcinoma in situ. METHODS: A retrospective case series including 14 patients
      treated with topical 5-FU cream, 13 patients with actinic keratosis and 1 patient
      with squamous cell carcinoma in situ. All patients were treated with an initial 2
      week course of twice-daily 5-FU application followed by mild ophthalmic
      antibiotic ointment applied until the epithelium healed. Additional 14-day
      courses of therapy were prescribed as clinically indicated if residual lesion was
      present or recurrence occurred. Charts were reviewed for location of lesion,
      marginal involvement, residual lesion at follow up, recurrence, and ocular
      adverse events. RESULTS: Six patients had upper eyelid lesions and 8 patients'
      lesions involved the lower eyelid. Marginal involvement was seen in 9 patients.
      All patients completed an initial 14-day course of twice-daily therapy. Five
      patients with actinic keratosis required a second 14-day course of therapy, 3 for
      residual lesion and 2 for recurrence at follow-up visits. The patient with
      squamous cell carcinoma in situ was treated with 3 courses. Average follow up was
      38 months with a range of 4 to 142 months. No clinically detectable lesion was
      seen in any patient at final follow up. Two patients experienced transient ocular
      adverse effects, including 1 patient with mild keratopathy and another with
      chemosis. CONCLUSIONS: The use of 5% 5-FU has been described in the treatment of
      noninvasive squamous neoplasia. This article describes the authors experience
      with lesions involving the eyelid, including the eyelid margin. Expected
      dermatologic inflammation occurred following treatment regimens, and mild
      transient ocular adverse effects were seen in 2 patients. Topical 5-FU may be
      useful in the treatment of periocular actinic keratoses and squamous cell
      carcinoma in situ.

PMID- 22460674
TI  - Basaloid follicular hamartoma of the eyelid.
AB  - An 86-year-old woman slowly developed a solitary 0.3 3 0.2-cm papule on the left
      lower eyelid. Complete excision disclosed a honeycombed lesion composed of
      interlacing basaloid strands unattached to the epidermis but rather extending
      into the dermis from a dilated hair follicle. The diagnosis was a solitary
      basaloid follicular hamartoma that can also occur in multiple, generalized, and
      inherited forms, sometimes with an associated systemic disease. The lesion
      exhibited a distinctive CD34-positive, mildly cellular myxoid stroma with many
      CK20-positive Merkel cells scattered within the basaloid cellular strands, which
      exhibited BCL-2 positivity only within the outermost cells bordering the stroma.
      These immunohistochemical features are the opposite of those displayed by basal
      cell carcinomas, which require more aggressive surgical management. Besides basal
      cell carcinomas, the differential diagnosis of basaloid follicular hamartoma
      includes fibrofolliculoma, tumor of the follicular infundibulum, poroma, and
      trabecular (Merkel cell) carcinoma.

PMID- 22460675
TI  - Primary orbital pleomorphic liposarcoma:  an aggressive course.
AB  - An aggressively poor course of primary orbital pleomorphic liposarcoma is
      presented. A 59-year-old man had suffered from multiple local recurrences and
      died 1 year after diagnosis of orbital pleomorphic liposarcoma. The tumor invaded
      into the brain only 10 months after exenteration. The patient had a history of
      partial tumor resection via anterior orbitotomy before total exenteration. It was
      assume that such an unusual poor course might be due to histologic findings,
      which revealed a high-grade pleomorphic liposarcoma with a high mitotic count
      (25/10 high-power field) or previous-done anterior orbitotomy, which was able to
      seed the tumor cells.

PMID- 22460676
TI  - Isolated unilateral linear epidermal nevus of the upper eyelid.
AB  - A 75-year-old man presented with a recurrent, unilateral, solitary, linear,
      corrugated lesion of the right upper eyelid of prolonged duration together with
      bilateral dermatochalasis. A re-excision with blepharoplasty was performed.
      Histopathologic analysis of the tissue revealed parallel linear arrays of
      papillomatosis and acanthosis with overlying basket-weave hyperkeratosis
      consistent with a linear epidermal nevus. Immunohistochemical studies disclosed
      normal numbers of intraepidermal melanocytes and Langerhans cells without Merkel
      cells or an increase in cycling keratinocytes. Although the term "nevus" is
      mostly used in conjunction with the common nevomelanocytic nevus, in fact nevi of
      other cutaneous cellular elements can occur on a malformational basis (such as
      sebaceous, eccrine, apocrine, pilar, and elastic fiber nevi). Ophthalmologists
      should be aware of epidermal nevi because they are rarely associated with
      cataracts, malignant cutaneous neoplasms, neurologic abnormalities, and
      musculoskeletal disorders. For focal lesions like the present one, local excision
      is appropriate. A select differential diagnosis of histopathologically related
      conditions is provided.

PMID- 22460677
TI  - The lift and fill lower blepharoplasty.
AB  - PURPOSE: To evaluate a series of patients who underwent combined lower
      transconjunctival blepharoplasty with fat repositioning and orbicularis muscle
      suspension, "The Lift and Fill Lower Blepharoplasty," as a means of improving
      lower eyelid, and eyelid/cheek interface aesthetics after surgery. METHODS: The
      authors retrospectively reviewed the charts of patients who underwent both
      transconjunctival lower blepharoplasty with fat repositioning and orbicularis
      muscle suspension over a 4-year period (2007-2010) from the 2 authors' practices.
      All patients with a history of previous eyelid surgery or trauma, eyelid or
      orbital inflammatory disease, and those with frank eyelid malposition are
      excluded. Additional procedures are noted and results and complications are
      reviewed. RESULTS: The study consists of 54 patients, of whom 42 are women, with
      an average age of 56 years and an average follow up of 19 months. Thirty patients
      had fat repositioning performed subperiosteally, and in 24 patients the
      dissection plane was preperiosteal. A skin excision was added in most patients
      and canthal suspension in approximately half of the patients. There were no cases
      of postoperative eyelid malposition or other significant complications. There
      were no appreciable differences in outcomes between the sub- or preperiosteal fat
      repositioning approaches. All patients were happy with their surgical outcome.
      CONCLUSION: The combination of transconjunctival lower blepharoplasty with fat
      repositioning, and orbicularis muscle suspension, "The Lift and Fill Lower
      Blepharoplasty," provides a reliable and reproducible aesthetic rejuvenation of
      the lower eyelid and its transition to the cheek.

PMID- 22460678
TI  - Removal of periocular eyelid veins by ambulatory phlebectomy with a regular
      crochet hook.
AB  - PURPOSE: To report the authors' experience using a regular crochet hook for
      removing blue periocular eyelid veins. METHODS: This article describes a new
      surgical procedure. Twenty-one procedures were performed in 15 patients who
      underwent removal of blue periocular lower eyelid veins with the implementation
      of a regular crochet hook. RESULTS: There was no clinical evidence of treatment
      failure during the subsequent 12 months, nor did any new veins appear.
      CONCLUSIONS: Periocular vein removal with a Crochet hook is safe and successful.
      It can augment blepharoplasty results.

PMID- 22460679
TI  - Discrepancy between fluorescence in situ hybridization and multiplex ligation
      dependent probe amplification in orbital recurrence of uveal melanoma 26 years
      after enucleation.
AB  - Cytogenetic analysis has transformed the management of uveal melanoma in recent
      years and allows categorization of such tumors into low-grade tumors with a
      favorable prognosis and high-grade tumors that metastasize with a fatal outcome.
      The authors report the case of a 73-year-old man who presented with recurrent
      melanoma in his left socket, 26 years after enucleation for uveal melanoma.
      Chromosomal analysis by multiplex ligation-dependent probe amplification revealed
      partial loss of chromosome 3 and gains in chromosomes 6 and 8, which were missed
      with fluorescence in situ hybridization. The patient developed multiple liver
      metastases 14 months after orbital exenteration and died 8 months later. To the
      best of authors' knowledge, this is the first report of late recurrence of uveal
      melanoma after enucleation, in which multiplex ligation-dependent probe
      amplification chromosomal analysis has been used. The case also highlights the
      limitations of fluorescence in situ hybridization and the benefits of multiplex
      ligation-dependent probe amplification, which is more reliable at predicting
      survival.

PMID- 22460680
TI  - Small-incision, sutureless repair of subconjunctival fat prolapse.
AB  - PURPOSE: To present a new, small-incision, sutureless surgical technique for the
      repair of subconjunctival fat prolapse. METHODS: This is a retrospective
      interventional case series. Four eyes of 3 patients who presented with prolapsed
      subconjunctival fat were surgically repaired using a small-incision, sutureless
      technique with fibrin glue. No prolapsed subconjunctival fat was excised.
      RESULTS: The surgical treatment of prolapsed subconjunctival fat using a small
      incision, sutureless technique with fibrin glue was successful in all 4 eyes.
      There have been no cases of recurrence of the prolapsed subconjunctival fat with
      a mean follow up of 31 months. CONCLUSIONS: Small-incision, sutureless
      repositioning of subconjunctival fat using fibrin glue is an effective new
      surgical technique for the management of prolapsed subconjunctival fat.

PMID- 22460681
TI  - Orbital invasion by squamous cell carcinoma arising in multiple epidermoid cysts.
AB  - Epidermal or epidermoid cysts usually are benign, solitary-growing masses located
      in the mid- or lower dermis. They are believed to derive from pilosebaceous units
      and are lined with an epidermis-like epithelium including a granular cell layer.
      The occurrence of multiple epidermal cysts on the scalp of nonsyndromic patients
      is extremely rare. Although the presence of squamous cell carcinoma in the wall
      of an isolated epidermoid cysts is well documented in the dermatological
      literature,, the authors are not aware of any article in the English literature
      describing orbital invasion by a carcinoma developed in isolated or multiple
      epidermoid cysts.

PMID- 22460682
TI  - Lower-eyelid tarsal ectropion repair with the Putterman ptosis clamp for lower
      eyelid conjunctival Mueller's muscle resection and lateral tendon tuck.
AB  - PURPOSE: To describe a technique for treatment of lower-eyelid tarsal ectropion
      using the Putterman ptosis clamp for excision of conjunctiva and Mueller's muscle
      as an adjunct to the lateral canthal tendon tuck. METHODS: Retrospective case
      series. Patients with moderate-to-severe lower-eyelid ectropion underwent lateral
      canthal tendon tucking followed by eversion of the lower eyelid over a desmarres
      retractor, separation of the lower-eyelid conjunctiva and Mueller's muscle from
      the underlying capsulopalpebral fascia, placement of the Putterman ptosis clamp,
      and resection of the incarcerated tissue followed by closure of the conjunctiva
      and the lateral canthus. RESULTS: Six patients and 8 eyes were studied. Of the 8
      eyes, 6 (75%) had complete resolution of tarsal ectropion and 2 (25%) had mild
      residual ectropion at last follow up. All 8 eyes (100%) had symptomatic
      improvement and 0 patients required re-operation. There were no noted severe
      adverse events. CONCLUSION: Lower-eyelid conjunctival Mueller's muscle resection
      using the Putterman ptosis clamp as an adjunct to lateral canthal tendon
      reinforcement is a safe and effective procedure in the treatment of lower-eyelid
      tarsal ectropion.

PMID- 22460683
TI  - Outcomes of dacryocystorhinostomy in patients with head and neck cancer treated
      with high-dose radiation therapy.
AB  - PURPOSE: To evaluate the outcomes of dacryocystorhinostomy (DCR) in patients with
      head and neck cancer treated with high-dose radiation therapy. METHODS: The
      clinical records of 43 consecutive patients with head and neck cancer who
      underwent DCR after high-dose external beam radiation therapy plus ablative
      surgery and/or chemotherapy between December 2001 and April 2011 were
      retrospectively reviewed. RESULTS: There were 23 men and 20 women. The median age
      was 56 years (range, 2-92 years). Thirty-one patients were Caucasian, 6 Hispanic,
      4 Asian, and 2 African American. Thirty patients (70%) presented with epiphora, 3
      (7%) with dacryocystitis, and 10 (23%) with both epiphora and dacryocystitis.
      Symptoms were unilateral in 34 patients (79%) and bilateral in 9 patients (21%).
      The most common primary cancer diagnoses were squamous cell carcinoma (n = 14),
      sarcoma (n = 8), adenoid cystic carcinoma (n = 4), and basal cell carcinoma (n =
      4). The most common primary tumor locations were the sinonasal cavity (n = 16),
      maxillary sinus (n = 9), palate (n = 3), and ethmoid sinus (n = 3). Thirty-seven
      patients (43 eyes) had DCR with silicone tube placement, and 6 patients (7 eyes)
      had DCR with Pyrex glass tube placement. Following DCR, 31 patients (72%) had
      resolution of their symptoms, and 12 patients (28%), 9 with silicone tubes and 3
      with Pyrex glass tubes, had persistent or recurrent epiphora (DCR failure). The
      most common reason for failure was significant residual canalicular and nasal
      mucosal scar tissue. Eight of these 12 patients underwent additional surgery,
      most commonly with placement of a Pyrex glass tube. Seven (35%) of the 20
      patients who underwent DCR less than 12 months after radiation therapy and 5
      (21%) of the 23 patients who underwent DCR at least 12 months after radiation
      therapy had recurrent symptoms. CONCLUSIONS: Dacryocystorhinostomy in patients
      with head and neck cancer previously treated with high-dose radiation therapy is
      generally successful, especially when delayed until at least 12 months after the
      completion of radiation therapy. A common reason for DCR failure after high-dose
      radiation therapy is severe canalicular and nasal mucosal scarring.

PMID- 22460684
TI  - A comparison of methods sensitive to interactions with small main effects.
AB  - Numerous genetic variants have been successfully identified for complex traits,
      yet these genetic factors only account for a modest portion of the predicted
      variance due to genetic factors. This has led to increased interest in other
      approaches to account for the "missing" genetic contributions to phenotype,
      including joint gene-gene or gene-environment analysis. A variety of methods for
      such analysis have been advocated. However, they have seldom been compared
      systematically. To facilitate such comparisons, the developers of the multifactor
      dimensionality reduction (MDR) simulated 100 data replicates for each of 96 two
      locus models displaying negligible marginal effects from either locus (16
      variations on each of six basic genetic models). The genetic models, based on a
      dichotomous phenotype, had varying minor allele frequencies and from two to eight
      distinct risk levels associated with genotype. The basic models were modified to
      include "noise" from combinations of missing data, genotyping error, genetic
      heterogeneity, and phenocopies. This study compares the performance of three
      methods designed to be sensitive to joint effects (MDR, support vector machines
      (SVMs), and the restricted partition method (RPM)) on these simulated data. In
      these tests, the RPM consistently outperformed the other two methods for each of
      the six classes of genetic models. In contrast, the comparison between other two
      methods had mixed results. The MDR outperformed the SVM when the true model had
      only a few, well-separated risk classes; while the SVM outperformed the MDR on
      more complicated models. Of these methods, only MDR has a well-developed user
      interface.

PMID- 22460685
TI  - A heterobimetallic metal-organic framework with tunable reactive metal sites:
      synthesis, characterization, and reactivity.
AB  - A technique for preparing heterobimetallic frameworks with tunable metal sites is
      demonstrated by the synthesis of a new two-dimensional metal-organic framework
      that is constructed from tetra(4-carboxyphenyl)porphyrin and Cd(II) species. The
      solid can be prepared in the presence of other divalent transition metals to
      yield the same framework with the smaller metal ions occupying the porphyrin
      ligands.

PMID- 22460686
TI  - Children's on-line processing of scrambling in Japanese.
AB  - This study investigates the on-line processing of scrambled sentences in Japanese
      by preschool children and adults using a combination of self-paced listening and
      speeded picture selection tasks. The effects of a filler-gap dependency,
      reversibility, and case markers were examined. The results show that both
      children and adults had difficulty in comprehending scrambled sentences when they
      were provided as reversible sentences. The reversibility effect was significant
      for children, whereas the interaction of reversibility and a filler-gap
      dependency was significant for adults. However, this does not indicate that
      children's parsing is fundamentally different from that of adults. For those
      children who processed the nominative and accusative case markers equally fast,
      the reactivation of the dislocated constituent was observed in the gap position.
      These results suggest that children's processing is basically the same as adults'
      in that their sentence processing is incremental and they parse a gap to form a
      filler-gap dependency.

PMID- 22460687
TI  - To what extent do we hear phonemic contrasts in a non-native regional variety?
      Tracking the dynamics of perceptual processing with EEG.
AB  - This combined ERP and behavioral experiment explores the dynamics of processing
      during the discrimination of vowels in a non-native regional variety. Southern
      listeners were presented with three word forms, two of which are encountered in
      both Standard and Southern French ([kot] and [kut]), whereas the third one exists
      in Standard but not Southern French ([kot]). EEG recordings suggest that all of
      the word pairs were discriminated by the listeners, although discrimination arose
      about 100ms later for the pairs which included the non-native word form than for
      those which contained word forms common to both French varieties. Behavioral data
      provide evidence that vowel discrimination is sensitive to the influence of the
      listeners' native phonemic inventory at a late decisional stage of processing.

PMID- 22460688
TI  - The effects of syntactic complexity on processing sentences in noise.
AB  - This paper discusses the influence of stationary (non-fluctuating) noise on
      processing and understanding of sentences, which vary in their syntactic
      complexity (with the factors canonicity, embedding, ambiguity). It presents data
      from two RT-studies with 44 participants testing processing of German sentences
      in silence and in noise. Results show a stronger impact of noise on the
      processing of structurally difficult than on syntactically simpler parts of the
      sentence. This may be explained by a combination of decreased acoustical
      information and an increased strain on cognitive resources, such as working
      memory or attention, which is caused by noise. The noise effect for embedded
      sentences is less than for non-embedded sentences, which may be explained by a
      benefit from prosodic information.

PMID- 22460689
TI  - Progression of dopamine transporter decline in patients with the Parkinson
      variant of multiple system atrophy: a voxel-based analysis of [123I]beta-CIT
      SPECT.
AB  - PURPOSE: We characterized the progression of dopamine transporter (DAT) decline
      in the striatum and extrastriatal regions including the midbrain and pons of
      patients with the Parkinson variant of multiple system atrophy (MSA-P) and
      compared longitudinally collected SPECT results with those in a cohort of
      patients with Parkinson's disease (PD). METHODS: Eight patients with MSA-P (age
      60.4 +/- 7.7 years, disease duration 2.4 +/- 1 years, UPDRS-III motor score 39.7
      +/- 4.7), and 11 patients with PD (age 61.2 +/- 6.4 years, disease duration 2.4
      +/- 1.1 years, UPDRS-III motor score 18.9 +/- 7.6) underwent a baseline and
      follow-up [(123)I]beta-CIT SPECT investigation within a time period of 1.3 years.
      Statistical parametric mapping (SPM) and a repetitive ANOVA design were used to
      objectively localize the decline in DAT availability without having to make an a
      priori hypothesis as to its location. RESULTS: SPM localized significant
      reductions in [(123)I]beta-CIT uptake in the dorsal brainstem of MSA-P patients
      compared to PD patients (p < 0.001) at baseline. Additional reductions in the DAT
      signal were localized in the caudate and anterior putamen of patients with MSA-P
      patients compared to PD patients at the follow-up examination (p < 0.001).
      Relative decline in tracer binding was evident in the caudate and anterior
      putamen of MSA-P patients compared to PD patients in the longitudinal analysis (p
      < 0.05), whereas no significant relative signal alteration was observed in the
      brainstem. CONCLUSION: In contrast to PD, the relatively higher rate of signal
      reduction in the caudate and anterior putamen is consistent with the faster
      disease progression reported in MSA-P. At baseline, the tracer uptake in the
      brainstem was already at very low levels in the MSA-P patients compared to that
      in healthy control subjects and did not progress any further, suggesting that the
      degeneration of monoaminergic neurons is almost complete early in the disease
      course.

PMID- 22460690
TI  - 131I gastric uptake with and without omeprazole in patients undergoing
      radioiodine therapy for differentiated thyroid carcinoma.

PMID- 22460691
TI  - Ultra-fast microwave-assisted hydrothermal synthesis of long vertically aligned
      ZnO nanowires for dye-sensitized solar cell application.
AB  - Long vertically aligned ZnO nanowire arrays were synthesized using an ultra-fast
      microwave-assisted hydrothermal process. Using this method, we were able to grow
      ZnO nanowire arrays at an average growth rate as high as 200 nm min(-1) for
      maximum microwave power level. This method does not suffer from the growth
      stoppage problem at long growth times that, according to our investigations, a
      normal microwave-assisted hydrothermal method suffers from. Longitudinal growth
      of the nanowire arrays was investigated as a function of microwave power level
      and growth time using cross-sectional FESEM images of the grown arrays. Effect of
      seed layer on the alignment of nanowires was also studied. X-ray diffraction
      analysis confirmed c-axis orientation and single-phase wurtzite structure of the
      nanowires. J-V curves of the fabricated ZnO nanowire-based mercurochrome
      sensitized solar cells indicated that the short-circuit current density is
      increased with increasing the length of the nanowire array. According to the UV
      vis spectra of the dyes detached from the cells, these increments were mainly
      attributed to the enlarged internal surface area and therefore dye loading
      enhancement in the lengthened nanowire arrays.

PMID- 22460693
TI  - The role of genetics in chronic wasting disease of North American cervids.
AB  - Chronic wasting disease (CWD) is a major concern for the management of North
      American cervid populations. This fatal prion disease has led to declines in
      populations which have high CWD prevalence and areas with both high and low
      infection rates have experienced economic losses in wildlife recreation and fears
      of potential spill-over into livestock or humans. Research from human and
      veterinary medicine has established that the prion protein gene (Prnp) encodes
      the protein responsible for transmissible spongiform encephalopathies (TSEs).
      Polymorphisms in the Prnp gene can lead to different prion forms that moderate
      individual susceptibility to and progression of TSE infection. Prnp genes have
      been sequenced in a number of cervid species including those currently infected
      by CWD (elk, mule deer, white-tailed deer, moose) and those for which
      susceptibility is not yet determined (caribou, fallow deer, sika deer). Over
      thousands of sequences examined, the Prnp gene is remarkably conserved within the
      family Cervidae; only 16 amino acid polymorphisms have been reported within the
      256 amino acid open reading frame in the third exon of the Prnp gene. Some of
      these polymorphisms have been associated with lower rates of CWD infection and
      slower progression of clinical CWD. Here we review the body of research on Prnp
      genetics of North American cervids. Specifically, we focus on known polymorphisms
      in the Prnp gene, observed genotypic differences in CWD infection rates and
      clinical progression, mechanisms for genetic TSE resistance related to both the
      cervid host and the prion agent and potential for natural selection for CWD
      resistance. We also identify gaps in our knowledge that require future research.

PMID- 22460692
TI  - Prion infection promotes extensive accumulation of alpha-synuclein in aged human
      alpha-synuclein transgenic mice.
AB  - In neurodegenerative disorders of the aging population, misfolded proteins, such
      as PrP(Sc), alpha-synuclein, amyloid beta protein and tau, can interact resulting
      in enhanced aggregation, cross seeding and accelerated disease progression.
      Previous reports have shown that in Creutzfeldt-Jakob disease and scrapie, alpha
      synuclein accumulates near PrP(Sc) deposits. However, it is unclear if pre
      existing human alpha-synuclein aggregates modified prion disease pathogenesis, or
      if PrP(Sc) exacerbates the alpha-synuclein pathology. Here, we inoculated
      infectious prions into aged alpha-synuclein transgenic (tg) and non-transgenic
      littermate control mice by the intracerebral route. Remarkably, inoculation of
      RML and mNS prions into alpha-synuclein tg mice resulted in more extensive and
      abundant intraneuronal and synaptic alpha-synuclein accumulation. In addition,
      infectious prions led to the formation of perineuronal alpha-synuclein deposits
      with a neuritic plaque-like appearance. Prion pathology was unmodified by the
      presence of alpha-synuclein. However, with the mNS prion strain there was a
      modest but significant acceleration in the time to terminal prion disease in mice
      having alpha-synuclein aggregates as compared with non-tg mice. Taken together,
      these studies support the notion that PrP(Sc) directly or indirectly promotes
      alpha-synuclein pathology.

PMID- 22460694
TI  - The stochastic properties of input spike trains control neuronal arithmetic.
AB  - In the nervous system, the representation of signals is based predominantly on
      the rate and timing of neuronal discharges. In most everyday tasks, the brain has
      to carry out a variety of mathematical operations on the discharge patterns.
      Recent findings show that even single neurons are capable of performing basic
      arithmetic on the sequences of spikes. However, the interaction of the two spike
      trains, and thus the resulting arithmetic operation may be influenced by the
      stochastic properties of the interacting spike trains. If we represent the
      individual discharges as events of a random point process, then an arithmetical
      operation is given by the interaction of two point processes. Employing a
      probabilistic model based on detection of coincidence of random events and
      complementary computer simulations, we show that the point process statistics
      control the arithmetical operation being performed and, particularly, that it is
      possible to switch from subtraction to division solely by changing the
      distribution of the inter-event intervals of the processes. Consequences of the
      model for evaluation of binaural information in the auditory brainstem are
      demonstrated. The results accentuate the importance of the stochastic properties
      of neuronal discharge patterns for information processing in the brain; further
      studies related to neuronal arithmetic should therefore consider the statistics
      of the interacting spike trains.

PMID- 22460695
TI  - Intracranial electrodes in the presurgical evaluation of epilepsy.
AB  - The resection of the epileptogenic area of brain is very important and useful for
      the treatment of uncontrolled epilepsy, especially for the patients with
      stereotyped partial seizures. The critical point for successful epilepsy surgery
      is the precise identification of epileptogenic zone. Actually, we cannot
      precisely localize the epileptogenic zone in about 25 % of patient with
      refractory seizures based on the noninvasive examination; thus for these
      patients, we mainly use the intracranial EEG to localize the epileptogenic zone
      which could be useful in 10-15 % of surgical candidates. The intracranial
      electrodes which are most used currently are depth electrodes, subdural strip
      electrodes, and subdural grid electrodes. The subject of this paper is to discuss
      and compare the indications, construction, insertion, interpretation,
      limitations, risks and accuracy of each of these methods.

PMID- 22460696
TI  - Increased axonal expression of nectin-1 in multiple sclerosis plaques.
AB  - Nectin-1 is a cell adhesion molecule that plays a role in interneuronal synapse
      formation, in axonal guidance during development and possibly in neuron-glia
      interactions. To better understand axonal changes in MS, nectin-1 expression was
      determined by immunohistochemistry in normal adult human cerebral white matter (n
      = 4) and in six MS plaques (three active and three inactive). The intensity of
      axonal nectin-1 expression was scored on a scale of 0 to 4+. In normal adult
      cerebral white matter, axons showed weak nectin-1 expression with a score of 1.25
      +/- 0.50. Axonal nectin-1 expression was significantly stronger within both
      active (score = 3.33 +/- 0.289, p = 0.001) and inactive (score = 2.16 +/- 0.29, p
      = 0.038) MS plaques than in normal white matter. Axons in white matter adjacent
      to MS plaques showed nectin-1 expression (score = 1.5 +/- 0.50) that was not
      statistically different from normal controls (p = 0.542). These findings raise
      the possibility that increased expression of nectin-1 in MS lesions plays a role
      in the pathogenesis of MS through participation in axonal responses to injury and
      mediation of altered neuron-glia interactions relevant to myelination.

PMID- 22460700
TI  - Going against the tide: increasing incidence of colorectal cancer among Koreans,
      Filipinos, and South Asians in California, 1988-2007.
AB  - OBJECTIVE: Colorectal cancer has declined markedly in California for all major
      racial/ethnic groups, including Asian/Pacific Islanders as a whole. Analyzing
      cancer data for Asian/Pacific Islanders collectively masks important differences
      that exist between individual Asian subgroups. This study examines secular, sex-,
      age-, and socioeconomic-specific trends in colorectal cancer incidence among six
      Asian subgroups-Chinese, Japanese, Filipino, Korean, Vietnamese, and South Asian
      to determine whether these groups experienced a decline in colorectal cancer
      incidence and to assess possible differences in colorectal cancer incidence
      trends among these groups. METHODS: Cases of invasive colorectal cancer diagnosed
      among Japanese, Chinese, Filipinos, Koreans, Vietnamese, and South Asians between
      1988 and 2007 were identified using the California Cancer Registry database.
      Secular, sex-, age-, and socioeconomic-specific trends in the age-adjusted
      colorectal cancer incidence rates for each Asian subgroup were examined using
      joinpoint analysis to estimate the annual percent change (APC). RESULTS: Among
      males, Koreans (APC, 3.6 %) were the only group that experienced a significant
      increase in colorectal cancer incidence. Among females, Koreans (APC, 2.7 %),
      South Asians (APC, 2.8 %), and Filipinos (APC, 1.6 %) experienced significant
      increases. Stratification by age at diagnosis revealed that Korean males (APC,
      3.4 %) and females (APC, 2.9 %) as well as Filipino females (APC, 1.8 %) aged 50
      years and older experienced a significant increase in colorectal cancer
      incidence. Korean males aged less than 50 years (APC, 3.4 %) also experienced a
      significant increase. Japanese (APC, -1.2 %) and Chinese (APC, -1.6 %) males aged
      50 years and older experienced a significant decrease in colorectal cancer
      incidence. Stratification by socioeconomic status (SES) revealed that Korean
      males (APC, 2.5 %) and females (APC, 2.9 %) as well as Filipino females (APC, 2.1
      %) in the lowest SES category experienced a significant increase in colorectal
      cancer incidence. Korean males (APC, 5.2 %) and females (APC, 3.1 %) as well as
      Filipino males (APC, 1.5 %) in the highest SES category also experienced a
      significant increase. Japanese males (APC, -2.5 %) and females (APC, -2.0 %) as
      well as Chinese males (APC, -2.8 %) and females (APC, -2.9 %) in the lowest SES
      category experienced a significant decrease. Chinese males in the middle (APC, 
      3.4 %) and highest (APC, -3.5 %) SES categories also experienced significant
      decreases in colorectal cancer incidence. CONCLUSIONS: In contrast to the
      decreasing trends in colorectal cancer incidence reported among all major
      racial/ethnic groups including Asian/Pacific Islanders, colorectal cancer is
      actually increasing among some Asian subgroups in California including Korean
      males and females, as well as South Asian and Filipino females. Furthermore, the
      colorectal cancer incidence trends for these Asian subgroups differ with respect
      to age at diagnosis and socioeconomic status. These findings suggest that more
      efforts need to be made to target these populations with culturally sensitive
      cancer prevention and screening programs. More research is needed to examine the
      differences in the colorectal cancer burden among these populations.

PMID- 22460701
TI  - Comparative analysis of clinicopathologic features, treatment, and survival of
      Asian women with a breast cancer diagnosis residing in the United States.
AB  - BACKGROUND: It has been established that disparities by ethnicity in the rates of
      breast cancer diagnoses and disease-specific survival (DSS) exist in the United
      States. However, few studies have assessed differences specifically between
      Asians and other ethnic groups or among Asian subgroups. METHODS: The authors
      used the Surveillance, Epidemiology, and End Results database to identify
      patients who were diagnosed with invasive breast cancer between 1988 and 2008.
      Clinicopathologic features, treatment, and DSS rates were compared among broad
      ethnic groups and among Asian subgroups. RESULTS: In total, there were 658,691
      patients in the study, including 511,701 non-Hispanic white (NHW) women (77.7%),
      57,890 black women (8.8%), 45,461 Hispanic white (HW) women (6.9%), and 43,639
      Asian women (6.6%). The Asian cohort was divided into the following subgroups:
      Filipino, Chinese, Japanese, Indian/Pakistani, Korean, Vietnamese,
      Hawaiian/Pacific Islander, and other. Patients in all the Asian subgroups, except
      Japanese, were younger at diagnosis than NHW patients. After adjustment for
      disease stage, Japanese patients diagnosed with stage I through III disease had
      better DSS rates than patients in the NHW group or in the other Asian subgroups.
      Hawaiian/Pacific Islander patients with stage III or IV disease had worse DSS
      rates than NHW patients and patients in the other Asian subgroups. All other
      Asian subgroups had DSS rates similar to the DSS rate in the NHW group. [Formula:
      see text] CONCLUSIONS: The current results indicated that disparities exist for
      Asian women with breast cancer who reside in the United States compared with NHW
      groups and among Asian subgroups. Differences in presenting clinicopathologic
      features may affect DSS rates, suggesting that further investigation of these
      disparities is warranted to increase early detection and treatment for specific
      subgroups.

PMID- 22460705
TI  - Transgenic HFE-dependent induction of hepcidin in mice does not require
      transferrin receptor-2.
AB  - Hereditary hemochomatosis (HH) is caused by mutations in several genes, including
      HFE and transferrin receptor-2 (TFR2). Loss of either protein decreases
      expression of the iron regulatory hormone hepcidin by the liver, leading to
      inappropriately high iron uptake from the diet, and resulting in systemic iron
      overload. In tissue culture, overexpressed HFE and TFR2 physically interact.
      Hepatocellular overexpression of Hfe in vivo increases hepcidin expression,
      despite an associated decrease in Tfr2. On this basis, we hypothesized that Tfr2
      would not be required for Hfe-dependent up-regulation of hepcidin. We show that
      hepatocellular overexpression of Hfe in Tfr2(Y245X/Y245X) mice leads to hepcidin
      induction eventuating in iron deficiency and a hypochromic, microcytic anemia.
      Furthermore, coimmunoprecipitation studies using liver lysates did not provide
      evidence for physical interaction between Hfe and Tfr2 in vivo. In conclusion, we
      demonstrate that Tfr2 is not essential for Hfe-mediated induction of hepcidin
      expression, supporting the possibility that TFR2 may regulate iron metabolism in
      an HFE-independent manner.

PMID- 22460708
TI  - Sensitivity of TRPM7 channels to Mg2+ characterized in cell-free patches of
      Jurkat T lymphocytes.
AB  - Transient receptor potential melastatin 7 (TRPM7) channels were originally
      identified electrophysiologically when depletion of cytosolic Mg(2+) resulted in
      the gradual development of an outwardly rectifying cation current. Conversely,
      inclusion of millimolar Mg(2+) in internal solutions prevented activation of
      these channels in whole cell patch clamp. We recently demonstrated that the
      Jurkat T-cell whole cell TRPM7 channels are inhibited by internal Mg(2+) in a
      biphasic manner, displaying high [IC(50(1)) ~ 10 MUM] and low [IC(50(2)) ~ 165
      MUM] affinity inhibitor sites. In that study, we had characterized the dependence
      of the maximum cell current density on intracellular Mg(2+) concentration. To
      characterize Mg(2+) inhibition in Jurkat T cells in more detail and compare it to
      whole cell results, we recorded single TRPM7 channels in cell-free membrane
      patches and investigated the dependence of their activity on Mg(2+) added on the
      cytoplasmic side. We systematically varied free Mg(2+) from 265 nM to 407 MUM and
      evaluated the extent of channel inhibition in inside-out patch for 58 patches. We
      found that the TRPM7 channel shows two conductance levels of 39.0 pS (gamma(1))
      and 18.6 pS (gamma(2)) and that both are reversibly inhibited by internal Mg(2+).
      The 39.0-pS conductance is the dominant state of the channel, observed most
      frequently in this recording configuration. The dose-response relation in inside
      out patches shows a steeper Mg(2+) dependence than in whole cell, yielding
      IC(50(1)) of 25.1 MUM and IC(50(2)) of 91.2 MUM.. Single-channel analysis shows
      that the primary effect of Mg(2+) in multichannel patches is a reversible
      reduction of the number of conducting channels (N(o)). Additionally, at high
      Mg(2+) concentrations, we observed a saturating 20% reduction in unitary
      conductance (gamma(1)). Thus Mg(2+) inhibition in whole cell can be explained by
      a drop in individual participating channels and a modest reduction in
      conductance. We also found that TRPM7 channels in some patches were not sensitive
      to this ion at submaximal Mg(2+) concentrations. Interestingly, Mg(2+) inhibition
      showed the property of use dependence: with repeated applications, Mg(2+) effect
      became gradually more potent, which suggests that Mg(2+) sensitivity of the
      channel is a dynamic characteristic that depends on other membrane factors.

PMID- 22460709
TI  - Wound healing: a role for HDACs in inhibition of fibroblast proliferation through
      repression of PDGF receptor-alpha. Focus on "Repression of PDGF-R-alpha after
      cellular injury involves TNF-alpha, formation of a c-Fos-YY1 complex, and
      negative regulation by HDAC".

PMID- 22460711
TI  - An osteoclastic protein-tyrosine phosphatase regulates the beta3-integrin, syk,
      and shp1 signaling through respective src-dependent phosphorylation in
      osteoclasts.
AB  - This study utilized the glutathione transferase (GST) pull-down assay to identify
      novel substrates of an osteoclastic protein-tyrosine phosphatase, PTP-oc.
      Consistent with the previous findings that the phosphorylated tyr-527 (pY527) of
      Src is a substrate of PTP-oc, the major protein pulled down with the phosphatase
      deficient (PD)-PTP-oc-GST trapping mutant in RAW264.7 cells was Src. The GST-PD
      PTP-oc also pulled down pY-Syk and pY-beta(3)-integrin, but not after PP2
      pretreatment. However, PTP-oc transgenic osteoclasts or PTP-oc-overexpressing
      RAW264.7 cells had elevated, and not reduced, levels of pY525/526-Syk and pY759
      beta(3) integrin, and the PTP-oc siRNA treatment drastically reduced levels of
      pY525/526 Syk and pY759-beta(3)-integrin in RAW264.7 cells. These findings are
      incompatible with the premise that they are substrates of PTP-oc. The PTP-oc
      dependent increases in pY525/526-Syk and pY759-beta(3)-integrin levels were
      completely blocked by PP2, indicating that these effects are secondary to PTP-oc
      mediated activation of the Src protein-tyrosine kinase (PTK). Overexpression of
      PTP-oc increased, and siRNA-mediated suppression of PTP-oc reduced, pY160-Vav1,
      pY173-Vav3, and pY783-PLCgamma levels, and Rac1 activation, which are downstream
      mediators of the ITAM/Syk signaling. Overexpression of PTP-oc also increased, and
      PTP-oc siRNA treatment decreased, the pY-Shp1 levels, which were blocked by PP2.
      Since Shp1 is a negative regulator of osteoclast activity and is a key mediator
      of the ITIM signaling, these findings suggest that PTP-oc is an upstream
      suppressor of the ITIM/Shp1 signaling through PTP-oc-induced Src-dependent Shp1
      phosphorylation. In summary, PTP-oc plays a central regulatory role in the
      concerted regulation of the beta(3)-integrin, the ITAM/Syk, and the ITIM/Shp1
      signaling indirectly through activation of Src PTK.

PMID- 22460712
TI  - Using lithium to probe sequential cation interactions with GAT1.
AB  - Li(+) interacts with the Na(+)/Cl(-)-dependent GABA transporter, GAT1, under two
      conditions: in the absence of Na(+) it induces a voltage-dependent leak current;
      in the presence of Na(+) and GABA, Li(+) stimulates GABA-induced steady-state
      currents. The amino acids directly involved in the interaction with the Na(+) and
      Li(+) ions at the so-called "Na2" binding site have been identified, but how
      Li(+) affects the kinetics of GABA cotransport has not been fully explored. We
      expressed GAT1 in Xenopus oocytes and applied the two-electrode voltage clamp and
      (22)Na uptake assays to determine coupling ratios and steady-state and presteady
      state kinetics under experimental conditions in which extracellular Na(+) was
      partially substituted by Li(+). Three novel findings are: 1) Li(+) reduced the
      coupling ratio between Na(+) and net charge translocated during GABA cotransport;
      2) Li(+) increased the apparent Na(+) affinity without changing its voltage
      dependence; 3) Li(+) altered the voltage dependence of presteady-state
      relaxations in the absence of GABA. We propose an ordered binding scheme for
      cotransport in which either a Na(+) or Li(+) ion can bind at the putative first
      cation binding site (Na2). This is followed by the cooperative binding of the
      second Na(+) ion at the second cation binding site (Na1) and then binding of
      GABA. With Li(+) bound to Na2, the second Na(+) ion binds more readily GAT1, and
      despite a lower apparent GABA affinity, the translocation rate of the fully
      loaded carrier is not reduced. Numerical simulations using a nonrapid equilibrium
      model fully recapitulated our experimental findings.

PMID- 22460710
TI  - New insights into the dynamic regulation of water and acid-base balance by renal
      epithelial cells.
AB  - Maintaining tight control over body fluid and acid-base homeostasis is essential
      for human health and is a major function of the kidney. The collecting duct is a
      mosaic of two cell populations that are highly specialized to perform these two
      distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor,
      the V2R, play a central role in regulating the urinary concentrating mechanism by
      stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical
      membrane of collecting duct principal cells. This increases epithelial water
      permeability and allows osmotic water reabsorption to occur. An understanding of
      the basic cell biology/physiology of AQP2 regulation and trafficking has informed
      the development of new potential treatments for diseases such as nephrogenic
      diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule
      acidification due to the activation of intercalated cells is also critical to
      organ function, and defects lead to several pathological conditions in humans.
      Therefore, it is important to understand how these "professional" proton
      secreting cells respond to environmental and cellular cues. Using epididymal
      proton-secreting cells as a model system, we identified the soluble adenylate
      cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the
      vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal
      intercalated cells also express sAC and respond to cAMP by increasing proton
      secretion, supporting the hypothesis that sAC could function as a luminal sensor
      in renal tubules to regulate acid-base balance. This review summarizes recent
      advances in our understanding of these fundamental processes.

PMID- 22460714
TI  - Deciphering the mechanisms of the Na+/H+ exchanger-3 regulation in organ
      dysfunction.
AB  - The Na(+)/H(+) exchanger-3 (NHE3) belongs to the mammalian NHE protein family and
      catalyzes the electro-neutral exchange of extracellular sodium for intracellular
      proton across cellular membranes. Its transport function is of essential
      importance for the maintenance of the body's salt and water homeostasis as well
      as acid-base balance. Indeed, NHE3 activity is finely regulated by a variety of
      stimuli, both acutely and chronically, and its transport function is fundamental
      for a multiplicity of severe and world-wide infection-pathological conditions.
      This review aims to provide a concise overview of NHE3 physiology and discusses
      the role of NHE3 in clinical conditions of prominent importance, specifically in
      hypertension, diabetic nephropathy, heart failure, acute kidney injury, and
      diarrhea. Study of NHE3 function in models of these diseases has contributed to
      the deciphering of mechanisms that control the delicate ion balance disrupted in
      these disorders. The majority of the findings indicate that NHE3 transport
      function is activated before the onset of hypertension and inhibited thereafter;
      NHE3 transport function is also upregulated in diabetic nephropathy and heart
      failure, while it is reported to be downregulated in acute kidney injury and in
      diarrhea. The molecular mechanisms activated during these pathological conditions
      to regulate NHE3 transport function are examined with the aim of linking NHE3
      dysfunction to the analyzed clinical disorders.

PMID- 22460713
TI  - Chemokine-like receptor 1 regulates skeletal muscle cell myogenesis.
AB  - The chemokine-like receptor-1 (CMKLR1) is a G protein-coupled receptor that is
      activated by chemerin, a secreted plasma leukocyte attractant and adipokine.
      Previous studies identified that CMKLR1 is expressed in skeletal muscle in a
      stage-specific fashion during embryogenesis and in adult mice; however, its
      function in skeletal muscle remains unclear. Based on the established function of
      CMKLR1 in cell migration and differentiation, we investigated the hypothesis that
      CMKLR1 regulates the differentiation of myoblasts into myotubes. In C(2)C(12)
      mouse myoblasts, CMKLR1 expression increased threefold with differentiation into
      multinucleated myotubes. Decreasing CMKLR1 expression by adenoviral-delivered
      small-hairpin RNA (shRNA) impaired the differentiation of C(2)C(12) myoblasts
      into mature myotubes and reduced the mRNA expression of myogenic regulatory
      factors myogenin and MyoD while increasing Myf5 and Mrf4. At embryonic day 12.5
      (E12.5), CMKLR1 knockout (CMKLR1(-/-)) mice appeared developmentally delayed and
      displayed significantly lower wet weights and a considerably diminished myotomal
      component of somites as revealed by immunolocalization of myosin heavy chain
      protein compared with wild-type (CMKLR1(+/+)) mouse embryos. These changes were
      associated with increased Myf5 and decreased MyoD protein expression in the
      somites of E12.5 CMKLR1(-/-) mouse embryos. Adult male CMKLR1(-/-) mice had
      significantly reduced bone-free lean mass and weighed less than the CMKLR1(+/+)
      mice. We conclude that CMKLR1 is essential for myogenic differentiation of
      C(2)C(12) cells in vitro, and the CMKLR1 null mice have a subtle skeletal muscle
      deficit beginning from embryonic life that persists during postnatal life.

PMID- 22460715
TI  - Calcium influx through a possible coupling of cation channels impacts skeletal
      muscle satellite cell activation in response to mechanical stretch.
AB  - When skeletal muscle is stretched or injured, satellite cells, resident myogenic
      stem cells positioned beneath the basal lamina of mature muscle fibers, are
      activated to enter the cell cycle. This signaling pathway is a cascade of events
      including calcium-calmodulin formation, nitric oxide (NO) radical production by
      NO synthase, matrix metalloproteinase activation, release of hepatocyte growth
      factor (HGF) from the extracellular matrix, and presentation of HGF to the
      receptor c-met, as demonstrated by assays of primary cultures and in vivo
      experiments. Here, we add evidence that two ion channels, the mechanosensitive
      cation channel (MS channel) and the long-lasting-type voltage-gated calcium-ion
      channel (L-VGC channel), mediate the influx of extracellular calcium ions in
      response to cyclic stretch in satellite cell cultures. When applied to 1-h
      stretch cultures with individual inhibitors for MS and L-VGC channels (GsMTx-4
      and nifedipine, respectively) or with a less specific inhibitor (gadolinium
      chloride, Gd), satellite cell activation and upstream HGF release were abolished,
      as revealed by bromodeoxyuridine-incorporation assays and Western blotting of
      conditioned media, respectively. The inhibition was dose dependent with a maximum
      at 0.1 MUM (GsMTx-4), 10 MUM (nifedipine), or 100 MUM (Gd) and canceled by
      addition of HGF to the culture media; a potent inhibitor for transient-type VGC
      channels (NNC55-0396, 100 MUM) did not show any significant inhibitory effect.
      The stretch response was also abolished when calcium-chelator EGTA (1.8 mM) was
      added to the medium, indicating the significance of extracellular free calcium
      ions in our present activation model. Finally, cation/calcium channel
      dependencies were further documented by calcium-imaging analyses on stretched
      cells; results clearly demonstrated that calcium ion influx was abolished by
      GsMTx-4, nifedipine, and EGTA. Therefore, these results provide an additional
      insight that calcium ions may flow in through L-VGC channels by possible coupling
      with adjacent MS channel gating that promotes the local depolarization of cell
      membranes to initiate the satellite cell activation cascade.

PMID- 22460716
TI  - A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal
      organic anion exporter.
AB  - The SLC17 anion transporter family comprises nine members that transport various
      organic anions in membrane potential (Deltapsi)- and Cl(-)-dependent manners.
      Although the transport substrates and physiological relevance of the majority of
      the members have already been determined, little is known about SLC17A4 proteins
      known to be Na(+)-phosphate cotransporter homologue (NPT homologue). In the
      present study, we investigated the expression and transport properties of human
      SLC17A4 protein. Using specific antibodies, we found that a human NPT homologue
      is specifically expressed and present in the intestinal brush border membrane.
      Proteoliposomes containing the purified protein took up radiolabeled p
      aminohippuric acid (PAH) in a Cl(-)-dependent manner at the expense of an
      electrochemical gradient of protons, especially Deltapsi, across the membrane.
      The Deltapsi- and Cl(-)-dependent PAH uptake was inhibited by
      diisothiocyanostilbene-2,2'-disulfonic acid and Evans blue, common inhibitors of
      SLC17 family members. cis-Inhibition studies revealed that various anionic
      compounds, such as hydrophilic nonsteroidal anti-inflammatory drugs, pravastatin,
      and urate inhibited the PAH uptake. Proteoliposomes took up radiolabeled urate,
      with the uptake having properties similar to those of PAH uptake. These results
      strongly suggested that the human NPT homologue acts as a polyspecific organic
      anion exporter in the intestines. Since SLC17A1 protein (NPT1) and SLC17A3
      protein (NPT4) are responsible for renal urate extrusion, our results reveal the
      possible involvement of a NPT homologue in urate extrusion from the intestinal
      duct.

PMID- 22460717
TI  - Heterologous co-expression of accA, fabD, and thioesterase genes for improving
      long-chain fatty acid production in Pseudomonas aeruginosa and Escherichia coli.
AB  - The goal of the present study was to increase the content of intracellular long
      chain fatty acids in two bacterial strains, Pseudomonas aeruginosa PA14 and
      Escherichia coli K-12 MG1655, by co-overexpressing essential enzymes that are
      involved in the fatty acid synthesis metabolic pathway. Recently, microbial fatty
      acids and their derivatives have been receiving increasing attention as an
      alternative source of fuel. By introducing two genes (accA and fabD) of P.
      aeruginosa into the two bacterial strains and by co-expressing with them the
      fatty acyl-acyl carrier protein thioesterase gene of Streptococcus pyogenes
      (strain MGAS10270), we have engineered recombinant strains that are efficient
      producers of long-chain fatty acids (C16 and C18). The recombinant strains
      exhibit a 1.3-1.7-fold increase in the production of long-chain fatty acids over
      the wild-type strains. To enhance the production of total long-chain fatty acids,
      we researched the carbon sources for optimized culture conditions and results
      were used for post-culture incubation period. E. coli SGJS17 (containing the
      accA, fabD, and thioesterase genes) produced the highest content of intracellular
      total fatty acids; in particular, the unsaturated fatty acid content was about 20
      fold higher than that in the wild-type E. coli.

PMID- 22460718
TI  - Surgical management of frontal sinus inverted papilloma: a systematic review.
AB  - OBJECTIVES/HYPOTHESIS: Surgical management of frontal sinus (FS) inverted
      papilloma (IP) remains a significant challenge. This study systematically reviews
      the FS IP literature to delineate outcomes based on surgical strategy. STUDY
      DESIGN: Systematic review. METHODS: Cases for inclusion were identified by
      literature query for the terms frontal sinus and inverted papilloma between 1995
      and 2010. Cases reported with sufficient outcomes data, defined as specific
      surgical approach and disease-free follow-up, were included. Statistical analysis
      was performed to identify significant risk factors for recurrence. The reported
      length of follow-up for each surgical approach was analyzed as an indicator of
      the strength of the reported literature for each approach. RESULTS: Fifty-seven
      cases were identified in 13 studies, with 49 cases deemed adequate for additional
      analysis. Twenty-four cases (49%) were primary, and 25 (51%) were secondary
      (residual or recurrent disease) IP. Bilateral FS involvement was reported in
      eight cases (16.3%). Surgical approaches employed included endoscopic frontal
      sinusotomy (EFS) in 21 (42.9%), endoscopic modified Lothrop (EML) in 10 (20.4%),
      osteoplastic flap in 13 (26.5%), and endoscopic trephination and EFS in five
      (10.2%) patients. The overall rate of recurrence was 22.4%. Mean follow-up time
      was 27 months. CONCLUSIONS: The recent reported literature of FS IP demonstrates
      high prevalence of recurrent and bilateral cases. Although statistical analysis
      of this accrued data is unable to delineate the best surgical approach for FS IP,
      more aggressive approaches frequently employed for secondary or bilateral disease
      may facilitate better disease control.

PMID- 22460719
TI  - Electron microscopy for mitochondrial density of tissue.

PMID- 22460720
TI  - The 47th Seminar of the European School of Nuclear Medicine (ESNM) May 13-15,
      2011, and the 7th International Congress of the Croatian Society of Nuclear
      Medicine May 15-18, 2011, Opatija, Croatia.

PMID- 22460721
TI  - EANM Marie Curie training project report 2011 University Hospital of Santiago de
      Compostela, Nuclear Medicine Department: Dr. Patricia Arce.

PMID- 22460722
TI  - [Assessment of injury severity at the accident scene by the emergency physician:
      utility of technical crash parameters: results of a pilot study].
AB  - BACKGROUND: Technical parameters of road traffic crashes are routinely documented
      by emergency physicians on scene. It is, however, unclear whether this
      information contributes to the estimation of injury severity of vehicle drivers.
      MATERIALS AND METHODS: In this study, three experienced emergency physicians were
      asked to predict the injury severity of vehicle drivers [categorized according to
      Injury Severity Score (ISS) values of <16 and >=16 as moderate to severe or life
      threatening] based on increasingly complex technical crash information, ranging
      from routine variables to photo documentation of the crash scene. A sample of 100
      cases (mean ISS 23.6+/-26.9) was obtained from the prospective database of an in
      depth technical and medical car crash research project conducted in the
      northeastern part of Germany. Statistical analysis comprised inter-rater
      agreement beyond chance (kappa values) and indicators of diagnostic test accuracy
      (i.e. sensitivity, specificity and so on). RESULTS: The inter-rater agreement of
      injury severity based on technical crash information was moderate to substantial
      (kappa 0.42-0.66). Amongst the three observers and various amounts of technical
      data, sensitivity ranged between 18 and 80%, and specificity ranged between 41
      and 89% in predicting the presence of major trauma. Presentation of photographs
      from the crash scene increased diagnostic accuracy. Still, the presented
      information led to a shift from a 50% prior probability of life-threatening
      injuries to a maximum of 40% in the negative and 67% in the positive case.
      CONCLUSION: Neither basic technical parameters that are easy to obtain after a
      car crash nor additional technical information markedly contribute to the
      emergency physician's estimation of a vehicle driver's injury severity. The
      presented results should be supported by a subsequent study including a larger
      sample.

PMID- 22460723
TI  - Trait motivation moderates neural activation associated with goal pursuit.
AB  - Research has indicated that regions of left and right dorsolateral prefrontal
      cortex (DLPFC) are involved in integrating the motivational and executive
      function processes related to, respectively, approach and avoidance goals. Given
      that sensitivity to pleasant and unpleasant stimuli is an important feature of
      conceptualizations of approach and avoidance motivation, it is possible that
      these regions of DLPFC are preferentially activated by valenced stimuli. The
      present study tested this hypothesis by using a task in which goal pursuit was
      threatened by distraction from valenced stimuli while functional magnetic
      resonance imaging data were collected. The analyses examined whether the impact
      of trait approach and avoidance motivation on the neural processes associated
      with executive function differed depending on the valence or arousal level of the
      distractor stimuli. The present findings support the hypothesis that the regions
      of DLPFC under investigation are involved in integrating motivational and
      executive function processes, and they also indicate the involvement of a number
      of other brain areas in maintaining goal pursuit. However, DLPFC did not display
      differential sensitivity to valence.

PMID- 22460724
TI  - Accurate imputation of rare and common variants in a founder population from a
      small number of sequenced individuals.
AB  - Advances in DNA sequencing technologies have greatly facilitated the discovery of
      rare genetic variants in the human genome, many of which may contribute to common
      disease risk. However, evaluating their individual or even collective effects on
      disease risk requires very large sample sizes, which involves study designs that
      are often prohibitively expensive. We present an alternative approach for
      determining genotypes in large numbers of individuals for all variants discovered
      in the sequence of relatively few individuals. Specifically, we developed a new
      imputation algorithm that utilizes whole-exome sequencing data from 25 members of
      the South Dakota Hutterite population, and genome-wide single nucleotide
      polymorphism (SNP) genotypes from >1,400 individuals from the same founder
      population. The algorithm relies on identity-by-descent sharing of phased
      haplotypes, a different strategy than the linkage disequilibrium methods found in
      most imputation algorithms. We imputed genotypes discovered in the sequence data
      to on average ~77% of chromosomes among the 1,400 individuals. Median R(2)
      between imputed and directly genotyped data was >0.99. As expected, many variants
      that are vanishingly rare in European populations have risen to larger
      frequencies in the founder population and would be amenable to single-SNP
      analyses.

PMID- 22460725
TI  - The TRPM8 ion channel comprises direct Gq protein-activating capacity.
AB  - The transient receptor potential (TRP) family of ion channels comprises receptors
      that are activated by a vast variety of physical as well as chemical stimuli. TRP
      channels interact in a complex manner with several intracellular signaling
      cascades, both up- and downstream of receptor activation. Investigating cascades
      stimulated downstream of the cold and menthol receptor TRPM8, we found evidence
      for both, functional and structural interaction of TRPM8 with Galphaq. We
      demonstrated menthol-evoked increase in intracellular Ca(2+) under extracellular
      Ca(2+)-free conditions, which was blocked by the PLC inhibitors U73122 or
      edelfosine. This metabotropic Ca(2+) signal could be observed also in cells
      expressing a channel-dead (i.e. non-conducting) or a chloride-conducting TRPM8
      pore mutant. However, this intracellular metabotropic Ca(2+) signal could not be
      detected in Galphaq deficient cells or in the presence of dominant-negative
      GalphaqX. Evidence for a close spatial proximity necessary for physical
      interaction of TRPM8 and Galphaq was provided by acceptor bleaching experiments
      demonstrating FRET between TRPM8-CFP and Galphaq-YFP. A Galphaq-YFP mobility
      assay (FRAP) revealed a restricted diffusion of Galphaq-YFP under conditions when
      TRPM8 is immobilized in the plasma membrane. Moreover, a menthol-induced and
      TRPM8-mediated G protein activation could be demonstrated by FRET experiments
      monitoring the dissociation of Galphaq-YFP from a Gbeta/Ggamma-CFP complex, and
      by the exchange of radioactive [(35)S]GTPgammaS for GDP. Our observations lead to
      a view that extends the operational range of the TRPM8 receptor from its function
      as a pure ion channel to a molecular switch with additional metabotropic
      capacity.

PMID- 22460726
TI  - A unifying diagnosis for pancytopenia, fever, hypoglycemia, and lactic acidosis.

PMID- 22460727
TI  - Vascular invasion in pancreatic cancer: predictive values for endoscopic
      ultrasound and computed tomography imaging.
AB  - OBJECTIVES: To evaluate the accuracy of endoscopic ultrasound (EUS) to determine
      vascular invasion in patients with pancreatic cancer. METHODS: Data were obtained
      prospectively from patients with a pancreatic lesion who underwent EUS, computed
      tomographic (CT) imaging, and surgery from March 2005 to March 2010. RESULTS:
      Fifty patients were included with a mean +/- SD age 61 +/- 11.5 years; 27 (54%)
      were women. The sensitivity, specificity, positive predictive value, and negative
      predictive value for EUS were the following: 61.1 (95% CI, 38.6-79.7), 90.3 (95%
      CI, 75.1-96.7), 78.6 (95% CI, 52.4-92.4), and 80 (95% CI, 64.1-90), respectively.
      The area under the curve for EUS and that for CT were 0.80 (95% CI, 0.68-0.92)
      and 0.74 (95% CI, 0.61-0.86), respectively. The positive predictive value for
      arterial invasion was 100% (95% CI, 61-100) for EUS and 60% (95% CI, 31.3-83.2)
      for CT. There were no complications associated with the EUS or the CT.
      CONCLUSION: Endoscopic US is a very good option to detect vascular invasion in
      patients with pancreatic cancer and is especially sensitive for arterial
      invasion. When it is available, we recommend that it be performed in addition to
      CT staging.

PMID- 22460728
TI  - A prospective evaluation of the effect of chronic proton pump inhibitor use on
      plasma biomarker levels in humans.
AB  - OBJECTIVE: Proton pump inhibitors (PPIs) are used primarily to treat
      gastroesophageal reflux disease. Proton pump inhibitor-induced achlorhydria
      increases circulating gastrin and chromogranin A (CGA). Chromogranin is a widely
      used biomarker for the diagnosis and follow-up for gut-based neuroendocrine
      tumors (NETs). Proton pump inhibitor-induced increases in CGA or gastrin may
      falsely suggest the presence of a NET when none exists. Pancreastatin, a fragment
      of CGA, is also commonly used to diagnose and follow NETs. We hypothesized that
      chronic PPI use would increase circulating plasma gastrin, CGA, and pancreastatin
      levels. METHODS: Thirty patients who used PPIs for 6 months or more (mean +/- SD
      duration, 3.1 +/- 2.5 years) and a separate control group of 30 patients who
      never used antacid medications were prospectively evaluated with plasma gastrin,
      CGA, and pancreastatin determinations. RESULTS: Chronic PPI use resulted in
      significant increases in CGA (15.1 +/- 11 vs 131 +/- 207 ng/mL; P = 0.005) and
      significant increases in gastrin (34.8 +/- 22.3 vs 167.8 +/- 136.2 pg/mL; P =
      0.001) compared to controls. In contrast, pancreastatin level in nonusers and
      chronic PPI users were identical (81.6 +/- 36.4 vs 89.4 +/- 43.4 pg/mL; P =
      0.46). CONCLUSIONS: Pancreastatin levels do not change with chronic PPI use and
      normal pancreastatin levels may be used to distinguish between drug-induced
      changes in biomarkers and tumor-related increases in circulating biomarkers.

PMID- 22460729
TI  - Parent and peer pathways to adolescent delinquency: variations by ethnicity and
      neighborhood context.
AB  - Effects of ethnicity and neighborhood quality often are confounded in research on
      adolescent delinquent behavior. This study examined the pathways to delinquency
      among 2,277 African American and 5,973 European American youth residing in high
      risk and low-risk neighborhoods. Using data from a national study of youth, a
      meditational model was tested in which parenting practices (parental control and
      maternal support) were hypothesized to influence adolescents' participation in
      delinquent behavior through their affiliation with deviant peers. The
      relationships of family and neighborhood risk to parenting practices and deviant
      peer affiliation were also examined. Results of multi-group structural equation
      models provided support for the core meditational model in both ethnic groups, as
      well as evidence of a direct effect of maternal support on delinquency. When a
      similar model was tested within each ethnic group to compare youths residing in
      high-risk and low-risk neighborhoods, few neighborhood differences were found.
      The results indicate that, for both African American and European American youth,
      low parental control influences delinquency indirectly through its effect on
      deviant peer affiliation, whereas maternal support has both direct and indirect
      effects. However, the contextual factors influencing parenting practices and
      deviant peer affiliation appear to vary somewhat across ethnic groups. Overall
      the present study highlights the need to look at the joint influence of
      neighborhood context and ethnicity on adolescent problem behavior.

PMID- 22460730
TI  - The effect of corporal punishment and verbal abuse on delinquency: mediating
      mechanisms.
AB  - While the link between parenting and delinquency is well established, there is
      less consensus among scholars with regards to the processes that account for this
      link. The current study had two objectives. The first was to disentangle the
      effects of African American parents' use of corporal punishment and verbal abuse
      on the conduct problems of their preteen children. The second was to investigate
      the mechanisms that explain this relationship, such as having low self-control or
      a hostile view of relationships, whereby these harsh parenting practices increase
      a youth's involvement in problem behavior. Further, we are interested in
      specifically addressing how these mechanisms may operate differently for males
      versus females. Analyses utilized structural equation modeling and longitudinal
      data spanning approximately 2.5 years from a sample of 704 (54.2 % female)
      African American children ages 10-12. The results indicated that verbal abuse was
      a more important predictor of conduct problems than corporal punishment.
      Additionally, we found that the mechanisms that mediated the impact of verbal
      abuse and corporal punishment on conduct problems varied by gender. For males,
      most of the effect of verbal abuse was mediated by low self-control, whereas
      anger/frustration was the primary mediator for females. Implications of these
      results and directions for future study are also discussed.

PMID- 22460731
TI  - Meta-analysis of treatment outcomes for sinonasal undifferentiated carcinoma.
AB  - OBJECTIVES: This study reviews the published outcomes regarding sinonasal
      undifferentiated carcinoma (SNUC) since the initial description in 1986. This
      article attempts to (1) understand and better describe the benefit and survival
      advantages associated with using radiation, chemotherapy, and surgical treatment
      and (2) support the recommendations of a treatment regimen with current available
      data in the literature. DATA SOURCES: Published English-language literature.
      REVIEW METHODS: A PubMed search for articles related to SNUC, along with the
      bibliographies of those articles to avoid missing articles. All articles were
      examined for an independent patient data meta-analysis. Thirty studies with 167
      cases from 1986 to October 2009 were identified. Demographics, disease extent,
      treatment, follow-up, and survival were analyzed. Patient cohorts mirroring
      Kadish staging were created. Kaplan-Meier curves were constructed. RESULTS:
      Follow-up range was 1 to 195 months (mean 23.4 months, median 15 months). At last
      follow-up, 26.3% of patients were alive with no evidence of disease, 21.0% were
      alive with disease, and 52.7% were dead of disease. The use of surgery was found
      to be the best single modality, but chemotherapy and radiation were important as
      adjuncts in extensive and aggressive disease. The presence of neck metastases was
      a poor prognostic sign. CONCLUSION: This study, containing the largest pool of
      SNUC patients, confirms a poor overall prognosis. The data suggest that the
      optimal treatment should include surgery, with radiation and/or chemotherapy as
      adjunct treatments. Neck disease in advanced local disease is a poor prognostic
      sign and merits aggressive treatment with multimodality therapy.

PMID- 22460732
TI  - Preoperative radiotherapy decreases lymph node yield of neck dissections for head
      and neck cancer.
AB  - OBJECTIVE: Determine if preoperative radiation therapy (RT) decreases the lymph
      node (LN) yield found at the time of neck dissection. STUDY DESIGN: Cross
      sectional analysis of Surveillance, Epidemiology, and End Results (SEER)
      database. METHODS: The SEER database was queried for patients presenting between
      1998 and 2002 with tonsil, oropharynx, hypopharynx, and laryngeal primary
      lesions. Tabulation was made by LNs examined, type of neck dissection performed,
      and timing of RT. Data from 2441 patients were retrieved. Descriptive statistics
      were used. RESULTS: One hundred sixty-one patients with RT preoperatively had a
      median of 20 LNs sampled (0-72). In total, 647 patients receiving no RT had a
      median of 27 LNs examined (0-88), and 1643 patients receiving RT postoperatively
      had a median of 29 (0-89). Mann-Whitney P = .02 was derived for RT preoperatively
      compared with no RT/RT postoperatively. CONCLUSION: In the head and neck,
      preoperative RT contributes to lower neck dissection LN yield.

PMID- 22460735
TI  - Stromal cells modulate TCL1 expression, interacting AP-1 components and TCL1
      targeting micro-RNAs in chronic lymphocytic leukemia.
AB  - The tissue microenvironment in chronic lymphocytic leukemia (CLL) has an
      increasingly recognized role in disease progression, but the molecular mechanisms
      of cross talk between CLL cells and their microenvironment remain incompletely
      defined. Bone marrow stromal cells (BMSC) protect CLL cells from apoptosis in a
      contact-dependent fashion, and have been used for the identification of key
      pathways such as the CXCR4-CXCL12 axis. To further dissect the molecular impact
      of BMSC on survival and the molecular activation signature of CLL cells, we co
      cultured CLL cells with different BMSC. Gene expression profiling of CLL cells
      revealed that the lymphoid proto-oncogene TCL1 was among the top genes
      upregulated in CLL cells by BMSC. TCL1 mRNA and protein upregulation by BMSC was
      paralleled by decreases of TCL1-interacting FOS/JUN, and confirmed by qRT-PCR,
      immunoblotting, immunoprecipitations, and flow cytometry. Stroma mediated
      increases in TCL1 were also associated with decreased levels of TCL1-regulatory
      micro-RNAs (miR-29b, miR-181b, miR-34b). These findings demonstrate that the
      microenvironment has a proactive role in the regulation of the known signaling
      enhancer and pro-survival molecule TCL1 in CLL. This provides a further rationale
      for therapeutically targeting the cross talk between CLL and BMSC.

PMID- 22460736
TI  - Deposition of photocatalytically active TiO2 films by inkjet printing of TiO2
      nanoparticle suspensions obtained from microwave-assisted hydrothermal synthesis.
AB  - In this paper, we present an inkjet printing approach suited for the deposition
      of photocatalytically active, transparent titanium oxide coatings from an
      aqueous, colloidal suspension. We used a bottom-up approach in which a microwave
      assisted hydrothermal treatment of titanium propoxide aqueous solutions in the
      presence of ethylenediaminetetraacetic acid and triethanolamine was used to
      create suspensions containing titania nanoparticles. Different inkjet printing
      set-ups, electromagnetic and piezoelectric driven, were tested to deposit the
      inks on glass substrates. The presence of preformed titania nanoparticles was
      expected to make it possible to reduce the heating temperature necessary to
      obtain the functionality of photocatalysis which can widen the application range
      of the approach to heat-sensitive substrates. We investigated the crystallinity
      and size of the obtained nanoparticles by electron microscopy and dynamic light
      scattering. The rheological properties of the suspensions were evaluated against
      the relevant criteria for inkjet printing and the jettability was analyzed. The
      photocatalytic activity of the obtained layers was analyzed by following the
      decomposition of a methylene blue solution under UV illumination. The influence
      of the heat treatment temperature on the film roughness, thickness and
      photocatalytic activity was studied. Good photocatalytic performance was achieved
      for heat treatments at temperatures as low as 150  degrees C, introducing the
      possibility of using this approach for heat-sensitive substrates.

PMID- 22460733
TI  - Annual Report to the Nation on the status of cancer, 1975-2008, featuring cancers
      associated with excess weight and lack of sufficient physical activity.
AB  - BACKGROUND: Annual updates on cancer occurrence and trends in the United States
      are provided through collaboration between the American Cancer Society (ACS), the
      Centers for Disease Control and Prevention (CDC), the National Cancer Institute
      (NCI), and the North American Association of Central Cancer Registries (NAACCR).
      This year's report highlights the increased cancer risk associated with excess
      weight (overweight or obesity) and lack of sufficient physical activity (<150
      minutes of physical activity per week). METHODS: Data on cancer incidence were
      obtained from the CDC, NCI, and NAACCR; data on cancer deaths were obtained from
      the CDC's National Center for Health Statistics. Annual percent changes in
      incidence and death rates (age-standardized to the 2000 US population) for all
      cancers combined and for the leading cancers among men and among women were
      estimated by joinpoint analysis of long-term trends (incidence for 1992-2008 and
      mortality for 1975-2008) and short-term trends (1999-2008). Information was
      obtained from national surveys about the proportion of US children, adolescents,
      and adults who are overweight, obese, insufficiently physically active, or
      physically inactive. RESULTS: Death rates from all cancers combined decreased
      from 1999 to 2008, continuing a decline that began in the early 1990s, among men
      and among women in most racial and ethnic groups. Death rates decreased from 1999
      to 2008 for most cancer sites, including the 4 most common cancers (lung,
      colorectum, breast, and prostate). The incidence of prostate and colorectal
      cancers also decreased from 1999 to 2008. Lung cancer incidence declined from
      1999 to 2008 among men and from 2004 to 2008 among women. Breast cancer incidence
      decreased from 1999 to 2004 but was stable from 2004 to 2008. Incidence increased
      for several cancers, including pancreas, kidney, and adenocarcinoma of the
      esophagus, which are associated with excess weight. CONCLUSIONS: Although
      improvements are reported in the US cancer burden, excess weight and lack of
      sufficient physical activity contribute to the increased incidence of many
      cancers, adversely affect quality of life for cancer survivors, and may worsen
      prognosis for several cancers. The current report highlights the importance of
      efforts to promote healthy weight and sufficient physical activity in reducing
      the cancer burden in the United States.

PMID- 22460737
TI  - Does prostate configuration affect the efficacy and safety of GreenLight HPSTM
      laser photoselective vaporization prostatectomy (PVP)?
AB  - We evaluate the efficacy and safety of GreenLight HPSTM laser photoselective
      vaporization prostatectomy (PVP) for the treatment of benign prostatic
      hyperplasia (BPH) with different prostate configuration. Patients were stratified
      into two groups: bilobe (group I) and trilobe (group II) BPH. Transurethral PVP
      was performed using a 120 W GreenLight HPSTM side-firing laser system. American
      Urological Association Symptom Score (AUASS), Quality of Life (QoL) score,
      maximum flow rate (Q max), and postvoid residual (PVR) were measured
      preoperatively and at 1 and 4 weeks and 3, 6, 12, 18, 24 and 36 months
      postoperatively. A number of 160 consecutive patients were identified (I: 86, II:
      74). Among the preoperative parameters, there were significant differences (p <
      0.05) in prostate volume (I: 46.0 +/- 19.8; II: 87.5 +/- 39.6 ml), Q max (I: 9.9
      +/- 3.9; II: 8.7 +/- 3.5 ml/sec), PVR (I: 59.2 +/- 124.6; II: 97.7 +/- 119.1 ml)
      and PSA (I: 1.4 +/- 1.4; II: 3.6 +/- 2.6 ng/ml), while AUASS and QoL were similar
      (p > 0.05). Significant differences (p < 0.05) in laser utilization (I: 9.5 +/-
      6.6; II: 19.5 +/- 11.6 min) and energy usage (I: 63.1 +/- 43.9; II: 132.5 +/-
      81.1 kJ) were noted. Clinical outcomes (AUASS, QoL, Q max, and PVR) showed
      immediate and stable improvement from baseline (p < 0.05) within each group, but
      no significant differences between the two groups were observed during the follow
      up period (p > 0.05). The incidences of adverse events were low and similar in
      both groups. Our experience suggests that BPH configuration has little effect on
      the efficacy and safety of GreenLight HPSTM laser PVP.

PMID- 22460739
TI  - Computational studies of complexation of nitrous oxide by borane-phosphine
      frustrated Lewis pairs.
AB  - Computational studies of complexes Ar(3)B-ONN-PR(3) derived from reactions
      between borane-phosphine frustrated Lewis pairs and N(2)O reveal several
      interesting facets. Natural resonance theory calculations support a change in the
      preferred resonance structure as the Lewis acidity of the borane increases.
      Potential constitutional isomers where phosphorus binds to oxygen and boron to
      nitrogen are predicted to be unstable with respect to loss of phosphine oxide and
      free N(2). Other constitutional isomers represent stationary points on the
      potential energy surface; most are considerably less stable than the observed
      complexes, but one is predicted to be as stable. This arises because the dominant
      resonance form combines alternating charge with the presence of a stabilizing NO
      double bond. The relationship between Lewis acidity and complex formation for a
      variety of boranes was explored; the results are consistent with the idea that
      greater Lewis acidity stabilizes both classical and frustrated Lewis acid-base
      pairs, but to differing degrees such that both types can entrap N(2)O.
      Calculations addressing the mechanism of complex formation suggest that N(2)O
      binds first through the nitrogen to the phosphine phosphorus of the FLP,
      whereupon boron coordinates the oxygen atom. Studies of the mechanism of the
      degenerate exchange reaction between (4-F-H(4)C(6))(3)B-ONN-P(t-Bu)(3) and
      B(C(6)H(4)-4-F)(3), involves a "transition state", with relatively short B-O
      distances, and so resembles a classical I(a) process. The process involves two
      barriers, one associated with bringing the incoming borane into proximity with
      the oxygen, and the other associated with isomerising from a ladle-shaped cis
      trans ct conformer to the observed trans-trans tt-type structure. The overall
      barrier for degenerate exchange was predicted to be between 65 and 110 kJ mol(
      1), in fair agreement with experiment. Similar studies of the reaction between (4
      F-H(4)C(6))(3)B-ONN-P(t-Bu)(3) and B(C(6)F(5))(3) indicate that this process more
      closely resembles a classical I(d) process, in that the "transition state"
      involves long B-O distances. Derivatization of the complexed NNO fragment appears
      possible; interaction between (F(5)C(6))(3)B-ONN-P(t-Bu)(3) and MeLi suggests
      stability for the ion pairs (F(5)C(6))(3)B-ON(Me)N-P(t-Bu)(3)(-)/Li(+) and
      (F(5)C(6))(3)B-ONN(Me)-P(t-Bu)(3)(-)/Li(+).

PMID- 22460738
TI  - Laser fluorescence of dentin caries covered with a novel nano-filled sealant.
AB  - The aim of the present study was to assess the possibility to measure caries
      induced laser fluorescence underneath a novel nano-filled fissure sealant. Sixty
      freshly extracted human teeth with occlusal dentine carious lesions were
      horizontally divided, exposing the respective lesion. Teeth were randomly
      assigned to three groups: (I) white fissure sealant with filler particles
      (Fissurit F, Voco), (II) clear fissure sealant without filler particles
      (Fissurit, Voco) and (III) novel experimental fissure sealant with nano-filler
      particles (Voco). Starting with a sealant thickness of 3 mm, laser fluorescence
      measurements (DIAGNOdent, KaVo) were performed after finishing the sealant
      surfaces with polishing papers, reducing the material at intervals of 0.5 mm
      until the sealant was removed completely. Evaluating a thickness of 0.5 mm, both
      the clear (83 % of the baseline fluorescence after fine grit polishing) and the
      white sealant (25 %) did not allow to measure baseline fluorescence (p < 0.05)
      with no fluorescence reduction in the experimental sealant group (p > 0.05). With
      increasing sealer thickness, fluorescence was influenced even by the experimental
      material (89 % of the baseline value at 1 mm). However, by using the experimental
      material, statistically significant higher fluorescence values than those for the
      other materials under study (p < 0.05) were obtained. Thicker sealant layers and
      coarse grit polishing caused a decrease of laser fluorescence in all groups (p <
      0.05). Employing the experimental nano-filled sealant, laser fluorescence
      measurements for caries detection can be performed through thicker sealant layers
      compared to conventional sealant materials. Thus, it might be possible to use
      this material to assess a caries progression underneath the sealant and
      administer an appropriate therapy in due time.

PMID- 22460740
TI  - Hamstring muscle strain injuries: what can we learn from history?

PMID- 22460743
TI  - Too dog tired to avoid danger: self-control depletion in canines increases
      behavioral approach toward an aggressive threat.
AB  - This study investigated whether initial self-control exertion by dogs would
      affect behavioral approach toward an aggressive threat. Dogs were initially
      required to exert self-control (sit still for 10 min) or not (caged for 10 min)
      before they were walked into a room in which a barking, growling dog was caged.
      Subject dogs spent 4 min in this room but were free to choose where in the room
      they spent their time. Approaching the unfamiliar conspecific was the predisposed
      response, but it was also the riskier choice (Lindsay, 2005). We found that
      following the exertion of self-control (in comparison with the control
      condition), dogs spent greater time in proximity to the aggressor. This pattern
      of behavior suggests that initial self-control exertion results in riskier and
      more impulsive decision making by dogs.

PMID- 22460742
TI  - Is the use of topical fluorescein helpful for management of CSF leakage?
AB  - OBJECTIVES/HYPOTHESIS: We aimed to evaluate the effectiveness of topical
      intranasal fluorescence application together with high-resolution computed
      tomography and magnetic resonance imaging and/or magnetic resonance
      cisternography for the preoperative diagnosis of cerebrospinal fluid (CSF)
      leakage and for intraoperative localization of CSF fistulas. We also assessed
      postoperative recurrence. STUDY DESIGN: Descriptive study. METHODS: Twenty-four
      cases underwent endonasal endoscopic repair for CSF leakage. Following intranasal
      topical application of fluorescein 10% to the middle turbinate-cribriform plate
      region and anterior wall of the sphenoid sinus, a color change of the fluorescein
      from yellow-brown to green was accepted as evidence of CSF leakage. A nasoseptal
      flap, collagen matrix, or fascia lata and septal cartilage graft were used for
      reconstruction of the CSF fistula. RESULTS: The use of topical fluorescein
      application was helpful in diagnosing CSF rhinorrhea preoperatively and locating
      the CSF fistula intraoperatively. One case had both ethmoid roof and sphenoid
      sinus defects, and this case underwent a second operation for closure of the
      sphenoid defect. All CSF leakages were successfully repaired by endoscopic
      endonasal surgery using a nasoseptal flap. CONCLUSIONS: Cases with traumatic CSF
      leakage pose a higher risk of meningitis than the cases with spontaneous CSF
      leakage. Topical application of fluorescein is highly specific and sensitive in
      identifying preoperative, intraoperative, and postoperative CSF leakage. It is a
      simple, quick, and sensitive technique. The surgeon should be vigilant for
      multiple defects.

PMID- 22460741
TI  - Revisiting the old link between infection and autoimmune disease with commensals
      and T helper 17 cells.
AB  - Genetic composition and major histocompatibility complex polymorphisms
      unequivocally predispose to autoimmune disease, but environmental factors also
      play a critical role in precipitating disease in susceptible individuals.
      Notorious among these has been microbial infection. Older studies describing
      associations between microbial infection and autoimmune disease are now followed
      by new studies demonstrating correlations between susceptibility to autoimmune
      disease and commensal colonization of the intestinal tract. T helper 17 (T(H)17)
      cells have gained a prominent role in autoimmune disease, and notably, their
      development within the intestine has been linked to colonization with specific
      commensal bacteria. Here, we consider current views on how microbes, T(H)17
      cells, and autoimmunity are connected. We speculate on how the intricate
      relationships among commensal, pathogen, and the host might ultimately determine
      susceptibility to autoimmune disease.

PMID- 22460745
TI  - Evidence for mental subdivision of space by infants: 3- to 4-month-olds
      spontaneously bisect a small-scale area into left and right categories.
AB  - Young infants have been shown to represent the left versus right spatial category
      relations of a target object and a vertical referent bar. In the present study,
      we examined whether infants would represent left versus right when the vertical
      bar was removed from the stimulus display. In Experiment 1, 3- to 4-month-olds
      who had been familiarized with stimuli depicting a diamond appearing in different
      locations to the left or right of the vertical midline displayed a mean novel
      category preference for a stimulus depicting the diamond on the opposite side of
      the midline. In Experiment 2, another group of 3- to 4-month-olds discriminated
      the within-category position changes of the diamond as it appeared to the left or
      right of the vertical midline. The results indicate that young infants can
      mentally bisect small-scale space into left versus right categories.

PMID- 22460744
TI  - Music-reading expertise alters visual spatial resolution for musical notation.
AB  - Crowding occurs when the perception of a suprathreshold target is impaired by
      nearby distractors, reflecting a fundamental limitation on visual spatial
      resolution. It is likely that crowding limits music reading, as each musical note
      is crowded by adjacent notes and by the five-line staff, similar to word reading,
      in which letter recognition is reduced by crowding from adjacent letters. Here,
      we tested the hypothesis that, with extensive experience, music-reading experts
      have acquired visual skills such that they experience a smaller crowding effect,
      resulting in higher music-reading fluency. Experts experienced a smaller crowding
      effect than did novices, but only for musical stimuli, not for control stimuli
      (Landolt Cs). The magnitude of the crowding effect for musical stimuli could be
      predicted by individual fluency in music reading. Our results highlight the role
      of experience in crowding: Visual spatial resolution can be improved specifically
      for objects associated with perceptual expertise. Music-reading rates are likely
      limited by crowding, and our results are consistent with the idea that experience
      alleviates these limitations.

PMID- 22460747
TI  - From the Editor-in-Chief.

PMID- 22460746
TI  - Two-phase stratified sampling designs for regional sequencing.
AB  - By systematic examination of common tag single-nucleotide polymorphisms (SNPs)
      across the genome, the genome-wide association study (GWAS) has proven to be a
      successful approach to identify genetic variants that are associated with complex
      diseases and traits. Although the per base pair cost of sequencing has dropped
      dramatically with the advent of the next-generation technologies, it may still
      only be feasible to obtain DNA sequence data for a portion of available study
      subjects due to financial constraints. Two-phase sampling designs have been used
      frequently in large-scale surveys and epidemiological studies where certain
      variables are too costly to be measured on all subjects. We consider two-phase
      stratified sampling designs for genetic association, in which tag SNPs for
      candidate genes or regions are genotyped on all subjects in phase 1, and a
      proportion of subjects are selected into phase 2 based on genotypes at one or
      more tag SNPs. Deep sequencing in the region is then applied to genotype phase 2
      subjects at sequence SNPs. We investigate alternative sampling designs for
      selection of phase 2 subjects within strata defined by tag SNP genotypes and
      develop methods of inference for sequence SNP variant associations using data
      from both phases. In comparison to methods that use data from phase 2 alone, the
      combined analysis improves efficiency.

PMID- 22460748
TI  - Definition of bone necrosis by the pathologist.
AB  - Osteonecrosis is a common disorder that may go clinically unrecognized or may
      result in the collapse of the architecture of bone, determining severe anatomic
      alterations of the involved site. Osteonecrosis is not a specific disease entity,
      but rather the result of a number of conditions ultimately leading to an
      impairment of blood supply to the bone tissue, although there is evidence that
      modifications of bone remodelling activity and weakening of bone structure with
      formation of microfractures are implicated as well. According to the site
      involved and to the factors promoting its development, the morbid anatomy and
      histopathology of osteonecrosis show a different appearance. This review
      discusses the main skeletal manifestations of osteonecrosis, including
      subarticular avascular necrosis of the femoral head and of the knee, as well as
      osteonecrosis of the jaw.

PMID- 22460749
TI  - Osteonecrosis in genetic disorders.
AB  - The avascular necrosis of bone is characterized by an abnormality of tissue that
      can occur whenever a disease process causes major cell stress. Some evidence
      supports a role for genetic factors in some avascular necrosis suggesting that
      gene mutations could play a role in the pathogenesis of osteonecrosis. These
      genetic studies provide hope that tools for identifying high risk patients will
      be available in the future.

PMID- 22460750
TI  - Pharmacokinetic profile of bisphosphonates in the treatment of metabolic bone
      disorders.
AB  - The pharmacokinetic profile of bisphosphonates is complex and depends on their
      potency in inhibiting bone resorption through their cellular effects and on the
      physicochemical action related to the interaction of these compounds with bone
      matrix. Amino-substituted bisphosphonates exert a more potent cellular effect on
      osteoclast via the inhibition of the mevalonate pathway, whereas non-nitrogen
      containing compounds exert a weaker effect deriving from the induction of
      intracellular metabolites in osteoclasts. For nitrogen-containing bisphosphonates
      there is a correlation between in vitro potency of inhibition of a specific
      enzyme, farnesyl pyrophosphate synthase, and their antiresorptive potency in
      vivo. Besides these effects on osteoclasts, bisphosphonates may in part mediate
      indirectly their antiresoprtive activity through several effects on osteoblasts
      and osteocytes. Different binding affinities of bisphopshonates to hydroxyapatite
      depend on both side chains structures and may explain how these drugs reach bone
      cells and exert their prolonged action in terms of adsorption and desorption
      processes. Clinical and animal-models derived data indicate that agents with high
      anti-resorptive potency, favourable bone binding characteristics and good
      tolerability can be used with long between-dose intervals to optimize therapeutic
      outcomes.

PMID- 22460751
TI  - Guidelines for the diagnosis of bisphosphonate-related osteonecrosis of the jaw
      (BRONJ).
AB  - Bisphosphonates are a class of agents used to treat osteoporosis and malignant
      bone metastases. Despite these benefits, osteonecrosis of the jaws has recently
      emerged as a significant complication in a subset of patients receiving these
      drugs. Based on a growing number of case reports and institutional reviews,
      bisphosphonate therapy may cause exposed and necrotic bone that is isolated to
      the jaw. This complication usually presents following simple dentoalveolar
      surgery and can cause a significant adverse effect on the quality of life for
      most patients. The pathogenesis for this complication appears to be related to
      the profound inhibition of osteoclast function and bone remodeling. This report
      will review the clinical signs and symptoms and risks associated with this new
      complication and provide a guideline for establishing a stage-specific diagnosis
      of BRONJ.

PMID- 22460752
TI  - Osteonecrosis of the myeloma patients treated with bisphosphonates.
AB  - Osteonecrosis of the jaw (ONJ) has been reported as uncommon but well recognised
      complication associated with bisphosphonate treatment. Multiple Myeloma (MM) is
      the pathology most frequently associated with ONJ in the medical and dental
      papers published over the last years (45% of the ONJ published cases). ONJ
      appears to be time-dependent with higher risk after long-term use of intravenous
      (i.v.) nitrogen containing bisphosphonates (eg, pamidronate, zoledronate) in
      older MM patients. The most frequent site of ONJ is the mandible and previous
      dental procedures may be a precipitating factor. Most of the ONJ cases presented
      clinical evidence of bone exposure and pain. There was no significant association
      between the occurrence of ONJ and the presence of osteolytic lesions, disease
      status and the use of thalidomide. Different treatments have been proposed,
      associated or not: medical therapy (eg, antimicrobial oral rinses, antibiotic and
      antimicotic), surgical therapy (eg, curettage or sequestrectomy) showing low
      healing rates and uncertain impact on the prognosis and on the outcome.

PMID- 22460753
TI  - Bisphosphonate-related osteonecrosis of the jaw: the Florence experience.
AB  - Aims. Bisphosphonates (BPs) are important therapeutic drugs in multiple myeloma
      and cancers with bone metastases. Bisphosphonate-Related Osteonecrosis of the Jaw
      (BRONJ) has been described as a potential side effect of the last generation BPs.
      The Authors evaluated clinical features, preventing measures and treatment
      strategies.Patients and methods. The Authors retrospectively analyzed 19 patients
      affected by malignant cancer in endovenous treatment with BPs. Fourteen patients
      were treated with zoledronate, 1 with pamidronate and 4 with both drugs for
      breast cancer (9 patients), multiple myeloma (6 patients), prostatic cancer (3
      patients) and colon cancer (1 patient).Results. The lenght of therapy was 5-36
      months before osteonecrosis was observed; in 15 patients BRONJ involved the
      mandible, in 2 the maxilla and in 2 both jaws. The trigger factors were tooth
      extractions, inadequate removable total denture, basic and advanced surgery, root
      canal treatment. Ten patients received non-surgical treatment, 7 patients minor
      surgical procedures and 2 patients a partial maxillectomy. Healing was achieved
      in all maxillary localization, and in one mandibular localization with partial
      maxillectomy.Conclusions. Prevention is the best important phase in the
      management of this pathology. Risk factors are the type of bisphosphonate and the
      length of exposure, while dental surgical procedures are trigger factors.
      Conservative treatment seems to be the best way to control BRONJ, but bone
      resection and soft tissue closure have to be performed when the lesion is
      refractory to conservative approach.

PMID- 22460754
TI  - Bisphosphonate - related osteonecrosis of the jaws: the point of view of the oral
      pathologist.
AB  - Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is mainly reported in
      patients with bone metastasis from a variety of solid tumors and disseminated
      multiple myeloma receiving iv bisphosphonates therapy. These patients represent
      95% of reported cases. The reported incidence of BRONJ is significantly higher
      with the iv preparations zoledronic acid and pamidronate while the risk appears
      to be minimal for patients receiving oral bisphosphonates. Currently, available
      published incidence data for BRONJ are based on retrospective studies and
      estimates of cumulative incidence range from 0.8% to 12%. The mandible is more
      commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by
      a dental surgical procedure. The signs and symptoms that may occur before the
      appearance of clinical evident osteonecrosis include changes in the health of
      periodontal tissues, non-healing mucosal ulcers, loose teeth and unexplained soft
      tissue infection. Although the definitive role of bisphosphonates remains to be
      elucidated, the alteration in bone metabolism together with surgical insult or
      prosthetic trauma appear to be key factors in the development of BRONJ. Tooth
      extraction as a precipitating event is a common observation in the reported
      literature. The significant benefits that bisphosphonates offer to patients
      clearly outbalance the risk of potential side effects; however, any patient for
      whom prolonged bisphosphonate therapy is indicated, should be provided with
      preventive dental care in order to minimize the risk of developing this severe
      condition. This article provides a review of current developments about the
      pathogenetic, clinical, management and preventive aspects of BRONJ.

PMID- 22460755
TI  - Prevention of bisphosphonates-induced osteonecrosis.
AB  - The osteonecrosis of the jaw is a new emergent disease, secondary to prolonged
      use of bisphosphonates. Bisphosphonates are a class of drug used in prevention
      and cure of bone diseases such as malignancy or bone metabolic diseases. In this
      article, we have tried to summarize, for patients taking IV or oral
      bisphosphonates-therapy, the most important informations on the pathogenesis and
      the risk factors in osteonecrosis of the jaw with particular attention about the
      preventive policies.

PMID- 22460756
TI  - Treatment of bisphosphonates-associated osteonecrosis.
AB  - This mini-review will focus on the management of a patient with bisphosphonate
      associated osteonecrosis (BON). In order to review the subject the authors report
      a case of a patient with prostate cancer and metastatic bone disease who was
      treated with zoledronic acid. Prior to cancer the patient was treated with
      risedronate for osteopenia but had discontinued this treatment when cancer was
      diagnosed. During the description of each aspect of the case, a discussion of the
      rationale used for the case management is presented with support of the available
      literature. Aspects of interest include the diagnosis of BON, the risk factor for
      BON for this particular patient, the decision making process for the management
      of acute and long-term oral cavity problems, and the introduction of high
      intensity laser therapy to help control pain and reduce infection and local
      bacterial load.

PMID- 22460757
TI  - Increased expression of extracellular matrix metalloproteinase inducer (CD147) in
      multiple myeloma: role in regulation of myeloma cell proliferation.
AB  - Multiple myeloma (MM) is preceded by the asymptomatic pre-malignant state,
      monoclonal gammopathy of undetermined significance (MGUS). Although MGUS patients
      may remain stable for years, they are at increased risk of progressing to MM. A
      better understanding of the relevant molecular changes underlying the transition
      from an asymptomatic to symptomatic disease state is urgently needed. Our studies
      show for the first time that the CD147 molecule (extracellular matrix
      metalloproteinase inducer) may be having an important biological role in MM. We
      first demonstrate that CD147 is overexpressed in MM plasma cells (PCs) vs normal
      and pre-malignant PCs. Next, functional studies revealed that the natural CD147
      ligand, cyclophilin B, stimulates MM cell growth. Moreover, when MM patient PCs
      displaying bimodal CD147 expression were separated into CD147(bright) and
      CD147(dim) populations and analyzed for proliferation potential, we discovered
      that CD147(bright) PCs displayed significantly higher levels of cell
      proliferation than did CD147(dim) PCs. Lastly, CD147-silencing significantly
      attenuated MM cell proliferation. Taken together, these data suggest that the
      CD147 molecule has a key role in MM cell proliferation and may serve as an
      attractive target for reducing the proliferative compartment of this disease.

PMID- 22460758
TI  - First-line imatinib mesylate in patients with newly diagnosed accelerated phase
      chronic myeloid leukemia.
AB  - Imatinib mesylate is the sole BCR-ABL tyrosine kinase inhibitor approved as first
      line treatment of accelerated-phase (AP) chronic myeloid leukemia (CML).
      Indication was based on the STI571 0109 study, in which imatinib favorably
      compared to historical treatments in patients failing prior therapies. The
      relevance of these results to currently newly diagnosed AP-CML patients remains
      unknown. We evaluated the benefit of imatinib in 42 newly diagnosed AP-CML
      patients. In all, 16 patients had hematological acceleration without chromosomal
      abnormalities in addition to the Philadelphia chromosome (ACAs; HEM-AP), 16
      solely had ACAs (ACA-AP) and 10 had hematological acceleration plus ACAs (HEM-AP
      + ACA). Major cytogenetic responses were achieved in 93.7% of HEM-AP patients,
      75% of patients with ACA-AP (P=NS) and 40% of patients with HEM-AP + ACA
      (P=0.0053). The 24-month failure-free survival rate was 87.5% in HEM-AP patients,
      43.8% in ACA-AP patients and 15% in HEM-AP + ACA patients (P=0.022). The 24-month
      estimate of progression-free survival was 100% in HEM-AP patients, 92.8% in ACA
      AP patients and 58.3% in HEM-AP + ACA patients (P=0.0052). In conclusion,
      frontline imatinib allows favorable outcomes in HEM-AP and ACA-AP patients but
      appears insufficient for patients with HEM-AP + ACA. Broader-target and/or more
      potent BCR-ABL tyrosine kinase inhibitors alone or in combination may be
      considered in this setting.

PMID- 22460759
TI  - Friends or foes? A review of peer influence on self-care and glycemic control in
      adolescents with type 1 diabetes.
AB  - OBJECTIVE: We reviewed studies published from 1990 to 2010 examining the relation
      of peer influence to diabetes outcomes for adolescents with type 1 diabetes.
      METHODS: We searched PsychInfo and MedLine databases and personal archives for
      studies meeting our criteria. 24 articles were included in the final review.
      RESULTS: Qualitative studies revealed that teens believe peers have an impact on
      diabetes behaviors, but quantitative findings are inconclusive. We found more
      evidence that social conflict was harmful than social support was helpful.
      Associations were more likely in studies that measured specific support and
      specific self-care variables. Studies addressing how individual differences
      interact with social context had promising findings. CONCLUSIONS: The literature
      linking peer relations to diabetes outcomes is mixed. Future research should
      consider moderator variables, expand the conceptualization of peer relationships,
      and consider interactions between person and social context.

PMID- 22460760
TI  - Xylitol prevents NEFA-induced insulin resistance in rats.
AB  - AIMS/HYPOTHESIS: Increased NEFA levels, characteristic of type 2 diabetes
      mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced
      insulin resistance was formerly attributed to decreased glycolysis, it is likely
      that glucose transport is the rate-limiting defect. Recently, the plant-derived
      sugar alcohol xylitol has been shown to have favourable metabolic effects in
      various animal models. Furthermore, its derivative xylulose 5-phosphate may
      prevent NEFA-induced suppression of glycolysis. We therefore examined whether and
      how xylitol might prevent NEFA-induced insulin resistance. METHODS: We examined
      the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5
      fold elevations in NEFA levels were induced with Intralipid/heparin infusions
      during 5 h euglycaemic-hyperinsulinaemic clamp studies in 24 conscious non
      diabetic Sprague-Dawley rats, with or without infusion of xylitol. RESULTS:
      Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly
      through suppression of glycogen synthesis. Co-infusion of xylitol prevented the
      NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although
      glycolysis was increased by xylitol infusion alone, there was minimal NEFA
      induced suppression of glycolysis, which was not affected by co-infusion of
      xylitol. CONCLUSIONS/INTERPRETATION: We conclude that xylitol prevented NEFA
      induced insulin resistance, with favourable effects on glycogen synthesis
      accompanying the improved insulin-mediated glucose uptake. This suggests that
      this pentose sweetener has beneficial insulin-sensitising effects.

PMID- 22460761
TI  - The pancreatic beta cell surface proteome.
AB  - The pancreatic beta cell is responsible for maintaining normoglycaemia by
      secreting an appropriate amount of insulin according to blood glucose levels. The
      accurate sensing of the beta cell extracellular environment is therefore crucial
      to this endocrine function and is transmitted via its cell surface proteome.
      Various surface proteins that mediate or affect beta cell endocrine function have
      been identified, including growth factor and cytokine receptors, transporters,
      ion channels and proteases, attributing important roles to surface proteins in
      the adaptive behaviour of beta cells in response to acute and chronic
      environmental changes. However, the largely unknown composition of the beta cell
      surface proteome is likely to harbour yet more information about these mechanisms
      and provide novel points of therapeutic intervention and diagnostic tools. This
      article will provide an overview of the functional complexity of the beta cell
      surface proteome and selected surface proteins, outline the mechanisms by which
      their activity may be modulated, discuss the methods and challenges of
      comprehensively mapping and studying the beta cell surface proteome, and address
      the potential of this interesting subproteome for diagnostic and therapeutic
      applications in human disease.

PMID- 22460762
TI  - Hepatocyte growth factor gene therapy enhances infiltration of macrophages and
      may induce kidney repair in db/db mice as a model of diabetes.
AB  - AIMS/HYPOTHESIS: We previously demonstrated hepatocyte growth factor (HGF) gene
      therapy was able to induce regression of glomerulosclerosis in diabetic
      nephropathy through local reparative mechanisms. The aim of this study was to
      test whether bone-marrow-derived cells are also involved in this HGF-induced
      reparative process. METHODS: We have created chimeric db/db mice as a model of
      diabetes that produce enhanced green fluorescent protein (EGFP) in bone marrow
      cells. We performed treatment with HGF gene therapy either alone or in
      combination with granulocyte-colony stimulating factor, in order to induce
      mobilisation of haematopoietic stem cells in these diabetic and chimeric animals.
      RESULTS: We find HGF gene therapy enhances renal expression of stromal-cell
      derived factor-1 and is subsequently associated with an increased number of bone
      marrow-derived cells getting into the injured kidneys. These cells are mainly
      monocyte-derived macrophages, which may contribute to the renal tissue repair and
      regeneration consistently observed in our model. Finally, HGF gene therapy is
      associated with the presence of a small number of Bowman's capsule parietal
      epithelial cells producing EGFP, suggesting they are fused with bone-marrow
      derived cells and are contributing to podocyte repopulation.
      CONCLUSIONS/INTERPRETATION: Altogether, our findings provide new evidence about
      the therapeutic role of HGF and open new opportunities for inducing renal
      regeneration in diabetic nephropathy.

PMID- 22460765
TI  - Nervous system development in Spinicaudata and Cyclestherida (Crustacea,
      Branchiopoda)--comparing two different modes of indirect development by using an
      event pairing approach.
AB  - Cladocera are the ecologically most important group within the Branchiopoda. They
      are unquestionably branchiopods but their evolutionary origin remains unclear.
      One favored explanation of their origin is that they evolved from a reproductive
      larva of a clam shrimp-like ancestor. To reveal a transformation and identify
      (potential) changes in chronology (heterochrony), we investigated and compared
      the development of representatives of two clam shrimp taxa, one of the
      Spinicaudata (Leptestheria dahalacensis) and one of the Cyclestherida
      (Cyclestheria hislopi), the sister group of Cladocera. Both taxa develop
      indirectly although the exact modes are quite different. The development of the
      nervous system, labeled and analyzed using immunohistochemical techniques and
      confocal microscopy, and that of the external morphology, scanned with an
      electron microscope, was investigated. L. dahalacensis hatch as a free-swimming
      nauplius and the nervous system and external morphology develop gradually. In C.
      hislopi, on the other hand, several internal and external structures develop
      before the hatching of a nonswimming embryo-like larva which is still carried in
      a dorsal brood pouch. The development in L. dahalacensis is directed from
      anterior to posterior, whereas in C. hislopi a more synchronous anterior and
      posterior differentiation is present. A comparison of both developmental
      sequences gives us the first indications of the evolutionary transformation which
      the Cladocera may have undergone from a clam shrimp-like ancestor.

PMID- 22460766
TI  - Compensation for cranial spill-in into the cerebellum improves quantitation of
      striatal dopamine D2/3 receptors in rats with prolonged [18F]-DMFP infusions.
AB  - The condition of steady-state receptor binding in positron emission tomography
      (PET) studies is best obtained through the use of a bolus plus steady-infusion
      paradigm. This is a particularly important consideration in the context of in
      vivo competition studies, where a pharmacological challenge can be administered
      during the interval of steady-state ligand binding, as in the case of [11C]
      raclopride studies with amphetamine challenge. However, the short half-life of
      11C imposes limits on the practical duration of constant infusions. Therefore, we
      chose to test [18F]-DMFP as a tracer for dopamine D2/3 receptors in rat striatum
      in the paradigm. Using a conventional bolus injection, the [18F]-DMFP BP(ND) was
      3.8 in striatum of anesthetized rats. When followed by a constant infusion, we
      obtained quasi-stable BP(ND) estimates of 4.5 within an interval of 45 min.
      During infusions lasting up to 4 h, BP(ND) declined progressively. This seemed
      due to the progressive spill-in of radioactivity from the cranium to the
      cerebellum reference region, despite optimized iterative reconstruction of the
      images. Therefore, we propose a new concept of compensation for this spill-in
      effect using pharmacokinetic considerations, without requiring high-resolution
      anatomical images. Challenge with amphetamine (1 and 4 mg/kg) evoked an ~25%
      reduction in BP(ND) . There was no clear evidence of dose-dependence in the
      striatal-binding changes, despite the considerably greater physiological effect,
      as documented by ECG. Thus, the general applicability of the bolus plus infusion
      method with [18F]-DMFP for small animal studies is impeded by the substantial
      labeling of the cranium. The cranial uptake was linear, indicating first-order
      kinetics for the enzymatic defluorination of the tracer. Based on this
      phenomenon, we developed an analytic method compensating for the effects of
      progressive cranial labeling on the estimation of specific binding in striatum.

PMID- 22460763
TI  - Pioglitazone and risk of bladder cancer among diabetic patients in France: a
      population-based cohort study.
AB  - AIMS/HYPOTHESIS: Previous studies have suggested an increased risk of bladder
      cancer with pioglitazone exposure. We aimed to investigate the association
      between pioglitazone exposure and bladder cancer in France. METHODS: This cohort
      study involved use of data from the French national health insurance information
      system (Systeme National d'Information Inter-regimes de l'Assurance Maladie;
      SNIIRAM) linked with the French hospital discharge database (Programme de
      Medicalisation des Systemes d'Information; PMSI). The cohort included patients
      aged 40 to 79 years who filled a prescription for a glucose-lowering drug in
      2006. The cohort was followed for up to 42 months. Pioglitazone exposure was
      modelled as a time-dependent variable and defined by having filled at least two
      prescriptions over a 6-month period. Incident cases of bladder cancer were
      identified by a discharge diagnosis of bladder cancer combined with specific
      aggressive treatment. Statistical analyses involved a multivariate Cox model
      adjusted for age, sex and exposure to other glucose-lowering drugs. RESULTS: The
      cohort included 1,491,060 diabetic patients, 155,535 of whom were exposed to
      pioglitazone. We found 175 cases of bladder cancer among exposed patients and
      1,841 among non-exposed patients. Incidence rates were 49.4 and 42.8 per 100,000
      person-years, respectively. Pioglitazone exposure was significantly associated
      with bladder cancer incidence (adjusted HR 1.22 [95% CI 1.05, 1.43]). We observed
      a dose-effect relationship, with a significantly increased risk for high
      cumulative doses (>= 28,000 mg, adjusted HR 1.75 [95% CI 1.22, 2.50]) and long
      duration of exposure (>= 24 months, adjusted HR 1.36 [1.04, 1.79]).
      CONCLUSIONS/INTERPRETATION: In this cohort of diabetic patients from France,
      pioglitazone exposure was significantly associated with increased risk of bladder
      cancer.

PMID- 22460768
TI  - Electrochemical properties of GaN nanowire electrodes--influence of doping and
      control by external bias.
AB  - We report on the electrochemical characteristics of GaN nanowire (NW) ensembles
      grown by plasma-assisted molecular beam epitaxy on Si111 substrates and on the
      influence of Si and Mg doping. The NW electrochemical properties in terms of
      surface capacitance (C(S)), surface resistance (R(S)) are extracted from
      electrochemical impedance spectra. While Mg doping of GaN NWs does not cause a
      significant variation of these quantities, an increase of the Si concentration
      leads to an increase of C(S) and a simultaneous decrease of R(S), indicating the
      presence of charge carriers in the NWs. According to the extracted values for
      R(S) and C(S) the NWs are classified into resistive and conductive. For
      conductive NWs charge transfer to a ferricyanide redox couple in the electrolyte
      is demonstrated and the ensemble average of the flatband voltage was determined.
      Variation of the lateral surface potential due to application of an external bias
      via the electrolyte is demonstrated.

PMID- 22460769
TI  - The combined effect of cations and anions on the dynamics of water.
AB  - We studied the orientational relaxation of the OD-stretch vibration of HDO
      molecules in concentrated solutions of alkali-halide salts (NaCl, NaI, CsCl and
      KI) in isotopically diluted water (4% D(2)O in H(2)O), using polarization
      resolved femtosecond infrared pump-probe spectroscopy (fs-IR). We were able to
      distinguish the orientational dynamics of the water molecules solvating the
      halide ions from the dynamics of the bulk water and the water solvating the
      cations. We found that the reorientation of the halide-bound molecules shows two
      strongly different components (2.0 +/- 0.3 ps and 9 +/- 1 ps), related to a
      wiggling motion of the OD group hydrogen-bonded to the anion, and rotational
      diffusion of the molecule over the charged anion surface, respectively. The
      relative amplitudes of the two components are dependent on the nature of both the
      anion and cation, and on the concentration. These results show that cations can
      have a profound effect on the solvation shell dynamics of their counter-ions.

PMID- 22460771
TI  - Development and validation of a neonatal intensive care parent satisfaction
      instrument.
AB  - OBJECTIVE: To develop and test the psychometric properties of the EMPATHIC-N
      (EMpowerment of PArents in THe Intensive Care-Neonatology) questionnaire
      measuring parent satisfaction. DESIGN: A psychometric study testing the
      reliability and validity of a parent satisfaction questionnaire by applying
      confirmatory factor analysis including standardized factor loadings and
      subsequently Cronbach's alpha reliability estimates across time, congruent
      validity, and nondifferential validity testing. SETTING: A 30-bed neonatal
      intensive care unit in a university hospital. PATIENTS: Two cohorts with a total
      of 441 parents whose child was admitted to the neonatal intensive care unit,
      January to December 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In
      the first cohort, 220 of 339 (65%) parents responded; in the second cohort, 59 of
      102 (58%) parents responded. Structural equation modeling and confirmatory factor
      analysis resulted in a sufficient model fit of 57 statements within five domains:
      Information, Care & Treatment, Organization, Parental Participation, and
      Professional Attitude. Standardized factor loading of these statements were
      between 0.58 and 0.91. Reliability measures, Cronbach's alpha, of the domains
      ranged from 0.82 to 0.95. Reliability across time showed no evidence of
      statistically significant differences between the domains. Congruent validity was
      confirmed by a good correlation (p = .01) between the domains and four general
      satisfaction questions. Nondifferential validity showed no significant effect
      sizes between the infants' characteristics and the domains, except between
      ventilated infants and parent participation statements and infants >=30 wks
      gestational age and organizational statements. CONCLUSIONS: The EMPATHIC-N
      questionnaire is a valid quality performance indicator to measure the delivered
      care as perceived by parents.

PMID- 22460770
TI  - Evaluation of asymmetric dimethylarginine, arginine, and carnitine metabolism in
      pediatric sepsis.
AB  - OBJECTIVE: Increased plasma concentrations of the endogenous nitric oxide
      synthase inhibitor, asymmetric dimethylarginine, decreased arginine
      bioavailability, and mitochondrial dysfunction have been reported in adult
      sepsis. We studied whether asymmetric dimethylarginine, arginine, and carnitine
      metabolism (a measure of mitochondrial dysfunction) are altered in pediatric
      sepsis and whether these are clinically useful biomarkers. DESIGN: : Prospective,
      observational study. SETTING: Pediatric intensive care unit at an academic
      medical center. PATIENTS: : Ninety patients <= 18 yrs old, 30 with severe sepsis
      or septic shock, compared with 30 age-matched febrile and 30 age-matched healthy
      control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma
      asymmetric dimethylarginine and whole blood arginine, citrulline, ornithine, and
      acylcarnitine:free carnitine ratio were measured daily for septic patients and
      once for control subjects using tandem mass spectrometry. Plasma asymmetric
      dimethylarginine concentration (median; interquartile range umol/L) on day 1 was
      lower in severe sepsis and septic shock (0.38; 0.30-0.56) compared with febrile
      (0.45; 0.40-0.59) and healthy (0.60; 0.54-0.67) control subjects (p < .001),
      although decreased asymmetric dimethylarginine was predominantly found in
      neutropenic patients. Day 1 arginine was lower in septic (10; interquartile
      range, 7-20 umol/L) compared with healthy patients (32; interquartile range, 23
      40; p < .001), and the arginine:ornithine ratio was decreased in sepsis,
      indicating increased arginase activity (an alternative pathway for arginine
      metabolism). The arginine:asymmetric dimethylarginine and acylcarnitine:free
      carnitine ratios did not differ between septic and control patients. Asymmetric
      dimethylarginine was inversely correlated with organ dysfunction by Pediatric
      Logistic Organ Dysfunction score (r = -0.50, p = .009), interleukin-6 (r = -0.55,
      p = .01), and interleukin-8 (r = -0.52, p = .03) on admission. Arginine,
      arginine:asymmetric dimethylarginine, and acylcarnitine:free carnitine were not
      associated with organ dysfunction or outcomes. CONCLUSIONS: Asymmetric
      dimethylarginine was decreased in pediatric sepsis and was inversely associated
      with inflammation and organ dysfunction. This suggests that inhibition of nitric
      oxide synthase by asymmetric dimethylarginine accumulation is unlikely to impact
      sepsis pathophysiology in septic children despite decreased arginine
      bioavailability. We did not find an association of asymmetric dimethylarginine
      with altered carnitine metabolism nor were asymmetric dimethylarginine, arginine,
      and acylcarnitine:free carnitine useful as clinical biomarkers.

PMID- 22460772
TI  - Epidemiology of sepsis in pediatric intensive care units: first Colombian
      multicenter study.
AB  - OBJECTIVES: In 2002, the Surviving Sepsis Campaign pointed out the need to
      recognize sepsis as an important cause of death and high economic and social
      costs. There are few epidemiologic studies of this disease in pediatrics and none
      in Colombia. The objective of this study was to describe the sociodemographic and
      clinical characteristics of patients with sepsis who were admitted at
      participating pediatric intensive care units. DESIGN: Prospective study. SETTING
      AND PATIENTS: A Web site, http://www.sepsisencolombia.com, was created, in which
      19 pediatric intensive care units from the ten principal cities in the country
      reported epidemiologic data about patients with sepsis between March 1, 2009, and
      February 28, 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were
      1,051 patients. Of these, 55% were male. Fifty-six percent came from urban areas.
      Fifty-six percent were <2 yrs of age. Seventy-six percent belonged to a low
      socioeconomic strata and 44% received government-subsidized health insurance.
      Forty-eight percent of patients had septic shock, 25% severe sepsis, and 27%
      sepsis. Forty-three percent were diagnosed with multiple organ dysfunction
      syndrome. In 54%, the infection was of respiratory origin followed by the abdomen
      as the site of origin in 18% of the patients. In almost 50%, the etiological
      agent was detected with Gram-negative bacteria being the most frequent and of
      highest mortality. Fifty percent had some type of relevant pathologic antecedent.
      Eleven percent had an invasive device on admission. Sixty-eight percent of the
      patients required mechanical ventilation. Mortality rate was 18%. The most
      important risk factors for mortality were age under 2 yrs, presence of shock or
      multiple organ dysfunction syndrome, and presence of Gram-negative bacteria.
      CONCLUSIONS: Sepsis is common in Colombian pediatric intensive care units. Clear
      risk factors for getting sick and dying from this disease were identified.
      Mortality resulting from this disease is considerable for a developing society
      like ours.

PMID- 22460773
TI  - Defining pediatric sepsis by different criteria: discrepancies in populations and
      implications for clinical practice.
AB  - OBJECTIVE: Pediatric patients with sepsis are identified using related but
      distinct criteria for clinical, research, and administrative purposes. The
      overlap between these criteria will affect the validity of extrapolating data
      across settings. We sought to quantify the extent of agreement among different
      criteria for pediatric severe sepsis/septic shock and to detect systematic
      differences between these cohorts. DESIGN: Observational cohort study. SETTING:
      Forty-two bed pediatric intensive care unit at an academic medical center.
      PATIENTS: A total of 1,729 patients <= 18 yrs-old. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: All patients were screened for severe sepsis or
      septic shock using consensus guidelines (research criteria), diagnosis by
      healthcare professionals (clinical criteria), and International Classification of
      Diseases, Ninth Revision, Clinical Modification codes (administrative criteria).
      Cohen's kappa determined the level of agreement among criteria, and patient
      characteristics were compared between cohorts. Ninety (5.2%) patients were
      identified by research, 96 (5.6%) by clinical, and 103 (6.0%) by administrative
      criteria. The kappa +/- standard error for pair-wise comparisons was 0.67 +/-
      0.04 for research-clinical, 0.52 +/- 0.05 for research-administrative, and 0.55
      +/- 0.04 for clinical-administrative. Of the patients in the clinical cohort, 67%
      met research and 58% met administrative criteria. The research cohort exhibited a
      higher Pediatric Index of Mortality-2 score (median, interquartile range 5.2, 1.6
      13.3) than the clinical (3.6, 1.1-6.2) and administrative (3.9, 1.0-6.0) cohorts
      (p = .005), an increased requirement for vasoactive infusions (74%, 57%, and 45%,
      p < .001), and a potential bias toward an increased proportion with respiratory
      dysfunction compared with clinical practice. CONCLUSIONS: Although research,
      clinical, and administrative criteria yielded a similar incidence (5%-6%) for
      pediatric severe sepsis/septic shock, there was only a moderate level of
      agreement in the patients identified by different criteria. One third of patients
      diagnosed clinically with sepsis would not have been included in studies based on
      consensus guidelines or International Classification of Diseases, Ninth Revision,
      Clinical Modification codes. Differences in patient selection need to be
      considered when extrapolating data across settings.

PMID- 22460774
TI  - Inspiratory capacity at inflation hold in ventilated newborns: a surrogate
      measure for static compliance of the respiratory system.
AB  - OBJECTIVE: To study appropriateness of respiratory system compliance calculation
      using an inflation hold and compare it with ventilator readouts of pressure and
      tidal volume as well as with measurement of compliance of the respiratory system
      with the single-breath-single-occlusion technique gained with a standard lung
      function measurement. DESIGN: Prospective clinical trial. SETTING: Level III
      neonatal unit of a university hospital. SUBJECTS: Sixty-seven newborns, born
      prematurely or at term, ventilated for a variety of pathologic conditions.
      INTERVENTIONS: A standardized sigh maneuver with a predefined peak inspiratory
      pressure of 30 cm H2O, termed inspiratory capacity at inflation hold, was
      applied. Using tidal volume, exhaled from inspiratory pause down to ambient
      pressure, as displayed by the ventilator, and predefined peak inspiratory
      pressure, compliance at inspiratory capacity at inflation hold conditions could
      be calculated as well as ratio of tidal volume and ventilator pressure using
      tidal volume and differential pressure at baseline ventilator settings: peak
      inspiratory pressure minus positive end-expiratory pressure. MEASUREMENTS AND
      MAIN RESULTS: For the whole cohort, the equation for the regression between tidal
      volume at inspiratory capacity at inflation hold and compliance of the
      respiratory system was: compliance of the respiratory system = 0.052 * tidal
      volume at inspiratory capacity at inflation hold - 0.113, and compliance at
      inspiratory capacity at inflation hold conditions was closely related to the
      standard lung function measurement method of compliance of the respiratory system
      (R = 0.958). In contrast, ratio of tidal volume and ventilator pressure per
      kilogram calculated from the ventilator readouts and displayed against compliance
      of the respiratory system per kilogram yielded a broad scatter throughout the
      whole range of compliance; both were only weakly correlated (R = 0.309) and also
      the regression line was significantly different from the line of identity (p <
      .05). Peak inspiratory pressure at study entry did not affect the correlation
      between compliance at inspiratory capacity at inflation hold conditions and
      compliance of the respiratory system. CONCLUSIONS: After a standard sigh
      maneuver, inspiratory capacity at inflation hold and the derived quantity
      compliance at inspiratory capacity at inflation hold conditions can be regarded
      as a valid, accurate, and reliable surrogate measure for standard compliance of
      the respiratory system in contrast to ratio of tidal volume and ventilator
      pressure calculated from the ventilator readouts during ongoing mechanical
      ventilation at respective ventilator settings.

PMID- 22460775
TI  - Radiation exposure from diagnostic imaging in the pediatric intensive care unit.
AB  - OBJECTIVE: To determine the range of radiation exposure from diagnostic imaging
      in children requiring mechanical ventilation. DESIGN: Prospective, observational.
      SETTING: Tertiary pediatric critical care unit. PATIENTS: We enrolled pediatric
      critical care unit patients requiring mechanical ventilation. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Thoracic radiation exposure while the
      patient was in the pediatric critical care unit was measured using a small,
      radiolucent dosimeter secured to the anterior chest wall. Demographic data,
      diagnoses, and number and type of radiographic procedures were recorded.
      Differences between exposures by admission diagnoses were analyzed by rank sum
      test. Relationships between exposure and risk factors were assessed using
      multiple linear regression and Pearson correlation. Sixty-nine subjects were
      enrolled over a 175-day period. Subjects experienced a mean (+/- SD) of 11 +/- 11
      days of mechanical ventilation during which they underwent a mean of 14 +/- 16
      chest radiographs and 5 +/- 4 other plain films. Subjects who had only plain
      radiographic studies (CXR group) had a median thoracic exposure of 1.02 (range,
      0.13-28.26) mGy and a median daily exposure of 0.16 (range, 0.02-1.99) mGy/day.
      Subjects who had computed tomography and/or fluoroscopy studies in addition to
      plain radiographs (CXR+ group) had a median total thoracic exposure of 3.71
      (range, 0.77-33.41) mGy and median daily exposure of 0.37 (range, 0.04-3.71)
      mGy/day, both of which were significantly higher than for subjects in the CXR
      group. There was no significant difference in average daily exposures according
      to admission diagnoses and daily exposure could not be predicted from a
      combination of variables, including age, body mass index, gender, or length of
      stay. Total number of radiologic studies was correlated, as expected, with
      duration of ventilation (r = 0.941, p < .0001). Exposure was significantly higher
      in patients who underwent computed tomography scans or fluoroscopy studies than
      in patients who only had plain radiography. CONCLUSIONS: Ventilated pediatric
      intensive care unit patients experienced an average daily thoracic radiation
      exposure above background environmental exposure and exposure varied widely, but
      exposures would not be expected to cause acute or chronic toxicity. Overall
      patient exposures were less than that received from 1 yr of natural background
      radiation.

PMID- 22460776
TI  - Antioxidant trace element reduction in an in vitro cardiopulmonary bypass
      circuit.
AB  - Many complications occurring after cardiac surgery are attributed to an acute
      increase in reactive oxygen and reactive nitrogen species, which under normal
      conditions are balanced by the antioxidant response. Two key enzymes of the
      antioxidant response, glutathione peroxidase (GPx) and superoxide dismutase
      (SOD), rely on trace elements for normal function. It was hypothesized that
      circulation of blood through the cardiopulmonary bypass (CPB) circuit would 1)
      reduce trace element levels and antioxidant function, 2) increase oxidative
      stress, and that 3) prepriming circuits with albumin would ameliorate trace
      element loss. This hypothesis was investigated by circulating fresh human whole
      blood in an in vitro CPB circuit. Plasma selenium, copper, and zinc levels were
      measured, as were SOD and GPx and oxidative stress by thiobarbituric acid
      reactive substances (TBARS). In spite of significant decreases in copper and zinc
      levels, SOD levels increased with time. Significant decreases in selenium were
      associated with a trend to increase TBARS but no change in GPx. Prepriming with
      albumin provided no benefit as it did not reduce trace element loss nor alter
      levels of oxidative stress. This study confirms that CPB circuits cause
      significant depletion of trace elements (selenium, copper, and zinc) necessary to
      maintain redox homeostasis. The loss of trace elements is a potential contributor
      to cardiac surgical morbidities, and further studies in the cardiac patient
      population are needed to investigate this.

PMID- 22460777
TI  - Molecular convergence of the parasitic plant species Cuscuta reflexa and
      Phelipanche aegyptiaca.
AB  - The parasitic plant species Cuscuta reflexa and Phelipanche aegyptiaca have
      independently developed parasitism, the former parasitizing on shoots and the
      latter attaching to roots. Regardless of these differences, the two species use
      similar organs, termed haustoria, to attach to the host plant. In this study, we
      show that this morphological similarity can be extended to the molecular level.
      An attAGP-promoter from Solanum lycopersicum, which is activated by Cuscuta
      infections, was also induced after infection by P. aegyptiaca. Furthermore, we
      show by validation of transcriptome sequencing data that the Phelipanche
      orthologue of a haustorium-specific Cuscuta gene, which codes for a cysteine
      proteinase, was activated in the early stages of Phelipanche invasion. Inhibition
      of the Phelipanche cysteine proteinase was achieved by 35S- or attAGP-promoter
      driven expression of its intrinsic inhibitory polypeptide. A reduction in P.
      aegyptiaca infection rates during experiments in flower pots and in an in vitro
      polybag system in comparison to controls was recorded.

PMID- 22460779
TI  - Positive child well-being: an index based on data for individual children.
AB  - Data from the 2007 National Survey of Children's Health are used to develop an
      index of positive child well-being that has several innovative and important
      characteristics. It distinguishes child well-being from contexts of child
      development; it is built with rich micro-data (rather than population-level macro
      data) to create unique measures of well-being for individual children; and it
      focuses on positive, rather than negative, aspects of development. These data can
      be aggregated to provide a perspective on the proportions of children in the
      population who are doing well on all, some, or no developmental domains. Based on
      child development theory and research, the index is constructed within a
      framework of four conceptually distinct developmental domains, each of which is
      comprised of three sub-domains. The index distinguishes among children in
      predicted directions, by poverty level and parental education. White children
      tend to do better than Hispanic or black children in all domains, though neither
      minority subgroup is consistently better or worse off than the other subgroup.
      Girls score slightly higher than boys on the index. About three in four children
      score positively on three or four domains. The index provides a composite,
      multidimensional view of positive child well-being that can be useful to
      researchers and policy analysts, and which addresses some weaknesses of other
      similar indices.

PMID- 22460778
TI  - Malignant ascites: pathophysiology and treatment.
AB  - Malignant ascites (MA) accompanies a variety of abdominal and extra-abdominal
      tumors. It is a primary cause of morbidity and raises several treatment
      challenges. MA has several symptoms, producing a significant reduction in the
      patient's quality of life: loss of proteins and electrolyte disorders cause
      diffuse oedema, while the accumulation of abdominal fluid facilitates sepsis.
      Treatment options include a multitude of different procedures with limited
      efficacy and some degree of risk. A Pubmed, Medline, Embase, and Cochrane Library
      review of medical, interventional and surgical treatments of MA has been
      performed. Medical therapy, primarily paracentesis and diuretics, are first-line
      treatments in managing MA. Paracentesis is widely adopted but it is associated
      with significant patient discomfort and several risks. Diuretic therapy is
      effective at the very beginning of the disease but efficacy declines with tumor
      progression. Intraperitoneal chemotherapy, targeted therapy, immunotherapy and
      radioisotopes are promising medical options but their clinical application is not
      yet completely elucidated, and further investigations and trials are necessary.
      Peritoneal-venous shunts are rarely used due to high rates of early mortality and
      complications. Laparoscopy and hyperthermic intraperitoneal chemotherapy (HIPEC)
      have been proposed as palliative therapy. Literature on the use of laparoscopic
      HIPEC in MA includes only reports with small numbers of patients, all showing
      successful control of ascites. To date, none of the different options has been
      subjected to evidence-based clinical trials and there are no accepted guidelines
      for the management of MA.

PMID- 22460780
TI  - A Bayesian integrative genomic model for pathway analysis of complex traits.
AB  - With new technologies, multiple types of genomic data are commonly collected on a
      single set of samples. However, standard analysis methods concentrate on a single
      data type at a time and ignore the relationships between genes, proteins, and
      biochemical reactions that give rise to complex phenotypes. In this paper, we
      propose a novel integrative model to incorporate multiple types of genomic data
      into an association analysis with a complex phenotype. The method combines path
      analysis and stochastic search variable selection into a Bayesian hierarchical
      model that simultaneously identifies both direct and indirect genomic effects on
      the phenotype. Results from a simulation study and application of the Bayesian
      model to a pharmacogenomic study of the drug gemcitabine demonstrate greater
      sensitivity to detect genomic effects in some simulation scenarios, when compared
      to the standard single data type analysis. Further research is required to extend
      and modify this integrative modeling framework to increase computational
      efficiency to best capitalize on the wealth of information available across
      multiple genomic data types.

PMID- 22460781
TI  - Epithelial-myoepithelial carcinoma of the maxillary sinus: a rare case.
AB  - Epithelial-myoepithelial carcinoma (EMC) is a rare tumor that commonly involves
      the salivary glands. EMC of the maxillary sinus is extremely rare. We describe
      here a case of a 50-year-old patient who presented with right cheek swelling for
      7 years and bilateral nasal obstruction and right nasal bleeding for 3 months. A
      pinkish polypoidal mass was seen in the right nasal cavity. Computed tomography
      scan revealed an expansile soft tissue mass in the right maxillary sinus with
      erosion of all of its walls. Histopathological examination of the excised
      specimen confirmed myoepithelial carcinoma with positive reaction to S-100 and
      smooth muscle actin. Subsequently, the patient developed regional nodal
      metastasis in the neck for which neck dissection was performed. Histopathology of
      the neck dissection specimen revealed metastatic EMC. EMC is rare tumor and a
      diagnostic dilemma. It should be considered in cases showing dual tumor cell
      population with clear cell change in histopathology. Common differential
      diagnosis includes metastatic renal cell carcinoma, acinic cell carcinoma,
      adenoid cystic carcinoma, mucoepidermoid carcinoma, oncocytoma, and sebaceous
      carcinoma. Laryngoscope, 2012.

PMID- 22460783
TI  - Synthetic routes to [Au(NHC)(OH)] (NHC = N-heterocyclic carbene) complexes.
AB  - New procedures for the synthesis of [Au(NHC)(OH)] are reported. Initially, a two
      step reaction via the digold complex [{Au(NHC)}(2)(MU-OH)][BF(4)] was probed,
      enabling the preparation of the novel [Au(SIPr)(OH)] complex and of its
      previously reported congener [Au(IPr)(OH)]. After further optimization, a one
      step procedure was developed.

PMID- 22460784
TI  - Role of mitochondrial activation in PACAP dependent neurite outgrowth.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) increases neurite
      outgrowth, although signaling via its receptor PACAP-specific receptor (PAC1R)
      has not been fully characterized. Because mitochondria also play an important
      role in neurite outgrowth, we examined whether mitochondria contribute to PACAP
      mediated neurite outgrowth. When mouse primary hippocampal neurons and Neuro2a
      cells were exposed to PACAP, neurite outgrowth and the mitochondrial membrane
      potential increased in both cell types. These results were reproduced using the
      PAC1R-specific agonist maxadilan and the adenylate cyclase activator forskolin,
      whereas the protein kinase A inhibitor H89 and mitochondrial uncoupling agent
      carbonyl cyanide m-chlorophenyl hydrazone (CCCP) inhibited these effects.
      Expression levels of peroxisome proliferator-activated receptor gamma coactivator
      1alpha (Pgc1alpha), a master regulator of mitochondrial activation, and its
      downstream effectors, such as cytochrome C and cytochrome C oxidase subunit 4,
      increased in response to PACAP. Knocking down Pgc1alpha expression using small
      interfering RNA or treatment with CCCP significantly attenuated neurite outgrowth
      and reduced the mitochondrial membrane potential in PACAP-treated cells. These
      data suggest that mitochondrial activation plays a key role in PACAP-induced
      neurite outgrowth via a signaling pathway that includes PAC1R, PKA, and
      Pgc1alpha.

PMID- 22460785
TI  - Crystal structure of the S100A4-nonmuscle myosin IIA tail fragment complex
      reveals an asymmetric target binding mechanism.
AB  - S100A4 is a member of the S100 family of calcium-binding proteins that is
      directly involved in tumor metastasis. It binds to the nonmuscle myosin IIA
      (NMIIA) tail near the assembly competence domain (ACD) promoting filament
      disassembly, which could be associated with increasing metastatic potential of
      tumor cells. Here, we investigate the mechanism of S100A4-NMIIA interaction based
      on binding studies and the crystal structure of S100A4 in complex with a 45
      residue-long myosin heavy chain fragment. Interestingly, we also find that S100A4
      binds as strongly to a homologous heavy chain fragment of nonmuscle myosin IIC as
      to NMIIA. The structure of the S100A4-NMIIA complex reveals a unique mode of
      interaction in the S100 family: A single, predominantly alpha-helical myosin
      chain is wrapped around the Ca(2+)-bound S100A4 dimer occupying both hydrophobic
      binding pockets. Thermal denaturation experiments of coiled-coil forming NMIIA
      fragments indicate that the coiled-coil partially unwinds upon S100A4 binding.
      Based on these results, we propose a model for NMIIA filament disassembly: Part
      of the random coil tailpiece and the C-terminal residues of the coiled-coil are
      wrapped around an S100A4 dimer disrupting the ACD and resulting in filament
      dissociation. The description of the complex will facilitate the design of
      specific drugs that interfere with the S100A4-NMIIA interaction.

PMID- 22460787
TI  - On the Waring problem for polynomial rings.
AB  - In this note we discuss an analog of the classical Waring problem for
      C[x0,x1,...,x(n)]. Namely, we show that a general homogeneous polynomial p ?
      C[x0,x1,...,x(n)] of degree divisible by k>=2 can be represented as a sum of at
      most k(n) k-th powers of homogeneous polynomials in C[x0,x1,...,x(n)].
      Noticeably, k(n) coincides with the number obtained by naive dimension count.

PMID- 22460786
TI  - Game-powered machine learning.
AB  - Searching for relevant content in a massive amount of multimedia information is
      facilitated by accurately annotating each image, video, or song with a large
      number of relevant semantic keywords, or tags. We introduce game-powered machine
      learning, an integrated approach to annotating multimedia content that combines
      the effectiveness of human computation, through online games, with the
      scalability of machine learning. We investigate this framework for labeling
      music. First, a socially-oriented music annotation game called Herd It collects
      reliable music annotations based on the "wisdom of the crowds." Second, these
      annotated examples are used to train a supervised machine learning system. Third,
      the machine learning system actively directs the annotation games to collect new
      data that will most benefit future model iterations. Once trained, the system can
      automatically annotate a corpus of music much larger than what could be labeled
      using human computation alone. Automatically annotated songs can be retrieved
      based on their semantic relevance to text-based queries (e.g., "funky jazz with
      saxophone," "spooky electronica," etc.). Based on the results presented in this
      paper, we find that actively coupling annotation games with machine learning
      provides a reliable and scalable approach to making searchable massive amounts of
      multimedia data.

PMID- 22460782
TI  - Resistance surveillance studies: a multifaceted problem--the fluoroquinolone
      example.
AB  - INTRODUCTION: This review summarizes data on the fluoroquinolone resistance
      epidemiology published in the previous 5 years. MATERIALS AND METHODS: The data
      reviewed are stratified according to the different prescription patterns by
      either primary- or tertiary-care givers and by indication. Global surveillance
      studies demonstrate that fluoroquinolone- resistance rates increased in the past
      several years in almost all bacterial species except Staphylococcus pneumoniae
      and Haemophilus influenzae causing community-acquired respiratory tract
      infections (CARTIs), as well as Enterobacteriaceae causing community-acquired
      urinary tract infections. Geographically and quantitatively varying
      fluoroquinolone resistance rates were recorded among Gram-positive and Gram
      negative pathogens causing healthcare-associated respiratory tract infections.
      One- to two-thirds of Enterobacteriaceae producing extended-spectrum beta
      lactamases (ESBLs) were fluoroquinolone resistant too, thus, limiting the
      fluoroquinolone use in the treatment of community- as well as healthcare-acquired
      urinary tract and intra-abdominal infections. The remaining ESBL-producing or
      plasmid-mediated quinolone resistance mechanisms harboring Enterobacteriaceae
      were low-level quinolone resistant. Furthermore, 10-30 % of H. influenzae and S.
      pneumoniae causing CARTIs harbored first-step quinolone resistance determining
      region (QRDR) mutations. These mutants pass susceptibility testing unnoticed and
      are primed to acquire high-level fluoroquinolone resistance rapidly, thus,
      putting the patient at risk. The continued increase in fluoroquinolone resistance
      affects patient management and necessitates changes in some current guidelines
      for the treatment of intra-abdominal infections or even precludes the use of
      fluoroquinolones in certain indications like gonorrhea and pelvic inflammatory
      diseases in those geographic areas in which fluoroquinolone resistance rates
      and/or ESBL production is high. Fluoroquinolone resistance has been selected
      among the commensal flora colonizing the gut, nose, oropharynx, and skin, so that
      horizontal gene transfer between the commensal flora and the offending pathogen
      as well as inter- and intraspecies recombinations contribute to the emergence and
      spread of fluoroquinolone resistance among pathogenic streptococci. Although
      interspecies recombinations are not yet the major cause for the emergence of
      fluoroquinolone resistance, its existence indicates that a large reservoir of
      fluoroquinolone resistance exists. Thus, a scenario resembling that of a
      worldwide spread of beta-lactam resistance in pneumococci is conceivable.
      However, many resistance surveillance studies suffer from inaccuracies like the
      sampling of a selected patient population, restricted geographical sampling, and
      undefined requirements of the user, so that the results are biased. The number of
      national centers is most often limited with one to two participating
      laboratories, so that such studies are point prevalence but not surveillance
      studies. Selected samples are analyzed predominantly as either hospitalized
      patients or patients at risk or those in whom therapy failed are sampled;
      however, fluoroquinolones are most frequently prescribed by the general
      practitioner. Selected sampling results in a significant over-estimation of
      fluoroquinolone resistance in outpatients. Furthermore, the requirements of the
      users are often not met; the prescribing physician, the microbiologist, the
      infection control specialist, public health and regulatory authorities, and the
      pharmaceutical industry have diverse interests, which, however, are not addressed
      by different designs of a surveillance study. Tools should be developed to
      provide customer-specific datasets. CONCLUSION: Consequently, most surveillance
      studies suffer from well recognized but uncorrected biases or inaccuracies.
      Nevertheless, they provide important information that allows the identification
      of trends in pathogen incidence and antimicrobial resistance.

PMID- 22460788
TI  - Dendritic connectivity controls biodiversity patterns in experimental
      metacommunities.
AB  - Biological communities often occur in spatially structured habitats where
      connectivity directly affects dispersal and metacommunity processes. Recent
      theoretical work suggests that dispersal constrained by the connectivity of
      specific habitat structures, such as dendrites like river networks, can explain
      observed features of biodiversity, but direct evidence is still lacking. We
      experimentally show that connectivity per se shapes diversity patterns in
      microcosm metacommunities at different levels. Local dispersal in isotropic
      lattice landscapes homogenizes local species richness and leads to pronounced
      spatial persistence. On the contrary, dispersal along dendritic landscapes leads
      to higher variability in local diversity and among-community composition.
      Although headwaters exhibit relatively lower species richness, they are crucial
      for the maintenance of regional biodiversity. Our results establish that
      spatially constrained dendritic connectivity is a key factor for community
      composition and population persistence.

PMID- 22460789
TI  - Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells
      predicts clinical outcome for human HER2+:ERalpha- breast cancer.
AB  - Human Epidermal Growth Factor Receptor 2-positive (HER2(+)) breast cancer (BC) is
      a highly aggressive disease commonly treated with chemotherapy and anti-HER2
      drugs, including trastuzumab. There is currently no way to predict which HER2(+)
      BC patients will benefit from these treatments. Previous prognostic signatures
      for HER2(+) BC were developed irrespective of the subtype or the hierarchical
      organization of cancer in which only a fraction of cells, tumor-initiating cells
      (TICs), can sustain tumor growth. Here, we used serial dilution and single-cell
      transplantation assays to identify MMTV-Her2/Neu mouse mammary TICs as
      CD24(+):JAG1(-) at a frequency of 2-4.5%. A 17-gene Her2-TIC-enriched signature
      (HTICS), generated on the basis of differentially expressed genes in TIC versus
      non-TIC fractions and trained on one HER2(+) BC cohort, predicted clinical
      outcome on multiple independent HER2(+) cohorts. HTICS included up-regulated
      genes involved in S/G2/M transition and down-regulated genes involved in immune
      response. Its prognostic power was independent of other predictors, stratified
      lymph node(+) HER2(+) BC into low and high-risk subgroups, and was specific for
      HER2(+):estrogen receptor alpha-negative (ERalpha(-)) patients (10-y overall
      survival of 83.6% for HTICS(-) and 24.0% for HTICS(+) tumors; hazard ratio =
      5.57; P = 0.002). Whereas HTICS was specific to HER2(+):ERalpha(-) tumors, a
      previously reported stroma-derived signature was predictive for
      HER2(+):ERalpha(+) BC. Retrospective analyses revealed that patients with
      HTICS(+) HER2(+):ERalpha(-) tumors resisted chemotherapy but responded to
      chemotherapy plus trastuzumab. HTICS is, therefore, a powerful prognostic
      signature for HER2(+):ERalpha(-) BC that can be used to identify high risk
      patients that would benefit from anti-HER2 therapy.

PMID- 22460790
TI  - p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity.
AB  - Insulin resistance is a key factor in the etiology of type 2 diabetes. Insulin
      stimulated glucose uptake is mediated by the glucose transporter 4 (GLUT4), which
      is expressed mainly in skeletal muscle and adipose tissue. Insulin-stimulated
      translocation of GLUT4 from its intracellular compartment to the plasma membrane
      is regulated by small guanosine triphosphate hydrolases (GTPases) and is
      essential for the maintenance of normal glucose homeostasis. Here we show that
      the p75 neurotrophin receptor (p75(NTR)) is a regulator of glucose uptake and
      insulin resistance. p75(NTR) knockout mice show increased insulin sensitivity on
      normal chow diet, independent of changes in body weight. Euglycemic
      hyperinsulinemic clamp studies demonstrate that deletion of the p75(NTR) gene
      increases the insulin-stimulated glucose disposal rate and suppression of hepatic
      glucose production. Genetic depletion or shRNA knockdown of p75(NTR) in
      adipocytes or myoblasts increases insulin-stimulated glucose uptake and GLUT4
      translocation. Conversely, overexpression of p75(NTR) in adipocytes decreases
      insulin-stimulated glucose transport. In adipocytes, p75(NTR) forms a complex
      with the Rab5 family GTPases Rab5 and Rab31 that regulate GLUT4 trafficking. Rab5
      and Rab31 directly interact with p75(NTR) primarily via helix 4 of the p75(NTR)
      death domain. Adipocytes from p75(NTR) knockout mice show increased Rab5 and
      decreased Rab31 activities, and dominant negative Rab5 rescues the increase in
      glucose uptake seen in p75(NTR) knockout adipocytes. Our results identify
      p75(NTR) as a unique player in glucose metabolism and suggest that signaling from
      p75(NTR) to Rab5 family GTPases may represent a unique therapeutic target for
      insulin resistance and diabetes.

PMID- 22460792
TI  - Anthropology of microbes.
AB  - We describe the need to further integrate the fields of human microbial ecology
      and anthropology and outline some of the potential goals and benefits of this
      collaborative work.

PMID- 22460791
TI  - Deficiency in DNA methylation increases meiotic crossover rates in euchromatic
      but not in heterochromatic regions in Arabidopsis.
AB  - Meiotic recombination is tightly regulated by cis- and trans-acting factors.
      Although DNA methylation and chromatin remodeling affect chromosome structure,
      their impact on meiotic recombination is not well understood. To study the effect
      of DNA methylation on the landscape of chromosomal recombination, we analyzed
      meiotic recombination in the decreased DNA methylation 1 (ddm1) mutant. DDM1 is a
      SWI2/SNF2-like chromatin-remodeling protein necessary for DNA methylation and
      heterochromatin maintenance in Arabidopsis thaliana. The rate of meiotic
      recombination between markers located in euchromatic regions was significantly
      higher in both heterozygous (DDM1/ddm1) and homozygous (ddm1/ddm1) backgrounds
      than in WT plants. The effect on recombination was similar for both male and
      female meiocytes. Contrary to expectations, ddm1 had no effect on the number of
      crossovers between markers in heterochromatic pericentric regions that underwent
      demethylation. These results are surprising, because the pericentromeric regions
      are hypermethylated and were expected to be the regions most affected by
      demethylation. Thus, DDM1 loss of function may trigger changes that enhance
      meiotic recombination in euchromatin regions but are not sufficient to induce the
      same events in heterochromatic segments. This work uncovers the repressive role
      of methylation on meiotic recombination in euchromatic regions and suggests that
      additional factors may have a role in controlling the suppression of
      recombination in heterochromatin.

PMID- 22460793
TI  - Active encoding of decisions about stimulus absence in primate prefrontal cortex
      neurons.
AB  - Judging the presence or absence of a stimulus is likely the most basic perceptual
      decision. A fundamental difference of detection tasks in contrast to
      discrimination tasks is that only the stimulus presence decision can be inferred
      from sensory evidence, whereas the alternative decision about stimulus absence
      lacks sensory evidence by definition. Detection decisions have been studied in an
      intentional, action-based framework, in which decisions were regarded as
      intentions to pursue particular actions. These studies have found that only
      stimulus-present decisions are actively encoded by neurons, whereas the decision
      about the absence of a stimulus does not affect default neuronal responses. We
      tested whether this processing mechanism also holds for abstract detection
      decisions that are dissociated from motor preparation. We recorded single-neuron
      activity from the prefrontal cortex (PFC) of monkeys performing a visual
      detection task that forced a report-independent decision. We not only found
      neurons that actively encoded the subjective decision of monkeys about the
      presence of a stimulus, but also cells responding actively for the decision about
      the absence of stimuli. These results suggest that abstract detection decisions
      are processed in a different way compared with the previously reported action
      based decisions. In a report-independent framework, neuronal networks seem to
      generate a second set of neurons actively encoding the absence of sensory
      stimulation, thus translating decisions into abstract categories. This mechanism
      may allow the brain to "buffer" a decision in a nonmovement-related framework.

PMID- 22460794
TI  - Fossils, molecules, divergence times, and the origin of Salamandroidea.

PMID- 22460796
TI  - Dam choices: analyses for multiple needs.

PMID- 22460795
TI  - Identification and validation of a gene causing cross-resistance between
      insecticide classes in Anopheles gambiae from Ghana.
AB  - In the last decade there have been marked reductions in malaria incidence in sub
      Saharan Africa. Sustaining these reductions will rely upon insecticides to
      control the mosquito malaria vectors. We report that in the primary African
      malaria vector, Anopheles gambiae sensu stricto, a single enzyme, CYP6M2, confers
      resistance to two classes of insecticide. This is unique evidence in a disease
      vector of cross-resistance associated with a single metabolic gene that
      simultaneously reduces the efficacy of two of the four classes of insecticide
      routinely used for malaria control. The gene-expression profile of a highly DDT
      resistant population of A. gambiae s.s. from Ghana was characterized using a
      unique whole-genome microarray. A number of genes were significantly
      overexpressed compared with two susceptible West African colonies, including
      genes from metabolic families previously linked to insecticide resistance. One of
      the most significantly overexpressed probe groups (false-discovery rate-adjusted
      P < 0.0001) belonged to the cytochrome P450 gene CYP6M2. This gene is associated
      with pyrethroid resistance in wild A. gambiae s.s. populations) and can
      metabolize both type I and type II pyrethroids in recombinant protein assays.
      Using in vitro assays we show that recombinant CYP6M2 is also capable of
      metabolizing the organochlorine insecticide DDT in the presence of solubilizing
      factor sodium cholate.

PMID- 22460797
TI  - Unification of reaction pathway and kinetic scheme for N2 reduction catalyzed by
      nitrogenase.
AB  - Nitrogenase catalyzes the reduction of N(2) and protons to yield two NH(3) and
      one H(2). Substrate binding occurs at a complex organo-metallocluster called FeMo
      cofactor (FeMo-co). Each catalytic cycle involves the sequential delivery of
      eight electrons/protons to this cluster, and this process has been framed within
      a kinetic scheme developed by Lowe and Thorneley. Rapid freezing of a modified
      nitrogenase under turnover conditions using diazene, methyldiazene (HN = N
      CH(3)), or hydrazine as substrate recently was shown to trap a common S = 1/2
      intermediate, designated I. It was further concluded that the two N-atoms of N(2)
      are hydrogenated alternately ("Alternating" (A) pathway). In the present work, Q
      band CW EPR and (95)Mo ESEEM spectroscopy reveal such samples also contain a
      common intermediate with FeMo-co in an integer-spin state having a ground-state
      "non-Kramers" doublet. This species, designated H, has been characterized by
      ESEEM spectroscopy using a combination of (14,15)N isotopologs plus (1,2)H
      isotopologs of methyldiazene. It is concluded that: H has NH(2) bound to FeMo-co
      and corresponds to the penultimate intermediate of N(2) hydrogenation, the state
      formed after the accumulation of seven electrons/protons and the release of the
      first NH(3); I corresponds to the final intermediate in N(2) reduction, the state
      formed after accumulation of eight electrons/protons, with NH(3) still bound to
      FeMo-co prior to release and regeneration of resting-state FeMo-co. A proposed
      unification of the Lowe-Thorneley kinetic model with the "prompt" alternating
      reaction pathway represents a draft mechanism for N(2) reduction by nitrogenase.

PMID- 22460798
TI  - The ubiquitin E3 ligase parkin regulates the proapoptotic function of Bax.
AB  - Autosomal recessive loss-of-function mutations within the PARK2 gene functionally
      inactivate the E3 ubiquitin ligase parkin, resulting in neurodegeneration of
      catecholaminergic neurons and a familial form of Parkinson disease. Current
      evidence suggests both a mitochondrial function for parkin and a neuroprotective
      role, which may in fact be interrelated. The antiapoptotic effects of parkin have
      been widely reported, and may involve fundamental changes in the threshold for
      apoptotic cytochrome c release, but the substrate(s) involved in parkin dependent
      protection had not been identified. Here, we demonstrate the parkin-dependent
      ubiquitination of endogenous Bax comparing primary cultured neurons from WT and
      parkin KO mice and using multiple parkin-overexpressing cell culture systems. The
      direct ubiquitination of purified Bax was also observed in vitro following
      incubation with recombinant parkin. We found that parkin prevented basal and
      apoptotic stress-induced translocation of Bax to the mitochondria. Moreover, an
      engineered ubiquitination-resistant form of Bax retained its apoptotic function,
      but Bax KO cells complemented with lysine-mutant Bax did not manifest the
      antiapoptotic effects of parkin that were observed in cells expressing WT Bax.
      These data suggest that Bax is the primary substrate responsible for the
      antiapoptotic effects of parkin, and provide mechanistic insight into at least a
      subset of the mitochondrial effects of parkin.

PMID- 22460799
TI  - TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene
      transcription via single-stranded DNA response elements.
AB  - TLS/FUS (TLS) is a multifunctional protein implicated in a wide range of cellular
      processes, including transcription and mRNA processing, as well as in both cancer
      and neurological disease. However, little is currently known about TLS target
      genes and how they are recognized. Here, we used ChIP and promoter microarrays to
      identify genes potentially regulated by TLS. Among these genes, we detected a
      number that correlate with previously known functions of TLS, and confirmed TLS
      occupancy at several of them by ChIP. We also detected changes in mRNA levels of
      these target genes in cells where TLS levels were altered, indicative of both
      activation and repression. Next, we used data from the microarray and
      computational methods to determine whether specific sequences were enriched in
      DNA fragments bound by TLS. This analysis suggested the existence of TLS response
      elements, and we show that purified TLS indeed binds these sequences with
      specificity in vitro. Remarkably, however, TLS binds only single-strand versions
      of the sequences. Taken together, our results indicate that TLS regulates
      expression of specific target genes, likely via recognition of specific single
      stranded DNA sequences located within their promoter regions.

PMID- 22460801
TI  - Hummingbird feeding mechanics: comments on the capillarity model.

PMID- 22460800
TI  - Dual functions of the Hsm3 protein in chaperoning and scaffolding regulatory
      particle subunits during the proteasome assembly.
AB  - The 26S proteasome, a molecular machine responsible for regulated protein
      degradation, consists of a proteolytic core particle (20S CP) associated with 19S
      regulatory particles (19S RPs) subdivided into base and lid subcomplexes. The
      assembly of 19S RP base subcomplex is mediated by multiple dedicated chaperones.
      Among these, Hsm3 is important for normal growth and directly targets the
      carboxyl-terminal (C-terminal) domain of Rpt1 of the Rpt1-Rpt2-Rpn1 assembly
      intermediate. Here, we report crystal structures of the yeast Hsm3 chaperone free
      and bound to the C-terminal domain of Rpt1. Unexpectedly, the structure of the
      complex suggests that within the Hsm3-Rpt1-Rpt2 module, Hsm3 also contacts Rpt2.
      We show that in both yeast and mammals, Hsm3 actually directly binds the AAA
      domain of Rpt2. The Hsm3 C-terminal region involved in this interaction is
      required in vivo for base assembly, although it is dispensable for binding Rpt1.
      Although Rpt1 and Rpt2 exhibit weak affinity for each other, Hsm3 unexpectedly
      acts as an essential matchmaker for the Rpt1-Rpt2-Rpn1 assembly by bridging both
      Rpt1 and Rpt2. In addition, we provide structural and biochemical evidence on how
      Hsm3/S5b may regulate the 19S RP association to the 20S CP proteasome. Our data
      point out the diverse functions of assembly chaperones.

PMID- 22460803
TI  - Dissipation and residues of flumetsulam in wheat and soil.
AB  - A residue analytical method for the determination of flumetsulam in wheat and
      soil was developed using gas chromatography with electron capture detector (GC
      ECD). The limit of detection of the analytical method was 0.001 ng, and the limit
      of quantification was 0.005, 0.01 mg/kg for soil and wheat grain, respectively.
      The mean recoveries from soil and wheat ranged from 83.85 % to 107.2 % with
      average relative standard deviation ranging from 1.87 % to 8.09 %. The method was
      successfully applied to determine the residual level and dissipation rate of
      flumetsulam in the soil and wheat. The half-life in soil was 23.1 days with a
      dissipation rate of 69 % over 35 days. At harvest time, the residue levels of
      flumetsulam in wheat grain and soil from high dosage plot were 0.031 and 0.045
      mg/kg, respectively. The flumetsulam residues could not be detected from low
      dosage plot. Direct confirmation of the analyte in real samples was achieved by
      GC-ECD.

PMID- 22460802
TI  - Active endocytosis and microtubule remodeling restore compressed pyramidal neuron
      morphology in rat cerebral cortex.
AB  - Previous studies have shown that compression alone reduced the thickness of rat
      cerebral cortex and apical dendritic lengths of pyramidal neurons without
      apparent cell death. Besides, decompression restored dendritic lengths at
      different degrees depending on duration of compression. To understand the
      mechanisms regulating dendritic shortening and lengthening upon compression and
      decompression, we applied transmission electron microscopy to examine microtubule
      and membrane structure of pyramidal neurons in rat sensorimotor cortex subjected
      to compression and decompression. Microtubule densities within apical dendritic
      trunks decreased significantly and arranged irregularly following compression for
      a period from 30 min to 24 h. In addition, apical dendritic trunks showed twisted
      contour. Two reasons are accounted for the decrease of microtubule density within
      this period. First, microtubule depolymerized and resulted in lower number of
      microtubules. Second, the twisted membrane widened the diameters of apical
      dendritic trunks, which also caused a decrease in microtubule density.
      Interestingly, these compression-induced changes were quickly reversed to control
      level following decompression, suggesting that these changes were accomplished
      passively. Furthermore, microtubule densities were restored to control level and
      the number of endocytotic vesicles significantly increased along the apical
      dendritic membrane in neurons subjected to 36 h or longer period of compression.
      However, decompression did not make significant changes on dendrites compressed
      for 36 h, for they had already shown straight appearance before decompression.
      These results suggest that active membrane endocytosis and microtubule remodeling
      occur in this adaptive stage to make the apical dendritic trunks regain their
      smooth contour and regular microtubule arrangement, similar to that of the normal
      control neurons.

PMID- 22460804
TI  - Crude oil-degradation and plasmid profile of nitrifying bacteria isolated from
      oil-impacted mangrove sediment in the Niger Delta of Nigeria.
AB  - The crude oil degradability and plasmid profile of autotrophic nitrifying
      bacteria, Nitrosomonas and Nitrobacter species, isolated from mangrove sediment
      in the Niger Delta of Nigeria were studied. The effects of temperature, pH and
      optical density on the utilization of different carbon sources by the bacteria
      were also investigated. Results showed that nitrifying bacteria could utilize
      kerosene, diesel oil, jet fuel and engine oil as carbon sources. None utilized
      hexane and xylene but moderate growth was observed in benzene, phenol and
      toluene. However, their ability to utilized crude oil varied both in rates of
      utilization and in growth profiles. Mixed culture of the isolates degrades 52 %
      of crude oil introduced into the medium followed by Nitrosomonas sp. with 40 %
      degradation. The least was Nitrobacter sp. with 20 % degradation. The ability of
      the autotrophs to degrade crude oil was found to be plasmid-mediated through
      curing experiment and electrophoresis. The size of the plasmid involved was
      estimated to be 23 kb. The high crude oil utilization of the mixed culture
      implies that nitrifying bacteria isolated from contaminated ecosystem are
      excellent crude oil degraders and can be harnessed for bioremediation purposes.

PMID- 22460805
TI  - Ferroelectric-carbon nanotube memory devices.
AB  - One-dimensional ferroelectric nanostructures, carbon nanotubes (CNT) and CNT
      inorganic oxides have recently been studied due to their potential applications
      for microelectronics. Here, we report coating of a registered array of aligned
      multi-wall carbon nanotubes (MWCNT) grown on silicon substrates by functional
      ferroelectric Pb(Zr,Ti)O3 (PZT) which produces structures suitable for commercial
      prototype memories. Microstructural analysis reveals the crystalline nature of
      PZT with small nanocrystals aligned in different directions. First-order Raman
      modes of MWCNT and PZT/MWCNT/n-Si show the high structural quality of CNT before
      and after PZT deposition at elevated temperature. PZT exists mostly in the
      monoclinic Cc/Cm phase, which is the origin of the high piezoelectric response in
      the system. Low-loss square piezoelectric hysteresis obtained for the 3D bottom
      up structure confirms the switchability of the device. Current-voltage mapping of
      the device by conducting atomic force microscopy (c-AFM) indicates very low
      transient current. Fabrication and functional properties of these hybrid
      ferroelectric-carbon nanotubes is the first step towards miniaturization for
      future nanotechnology sensors, actuators, transducers and memory devices.

PMID- 22460806
TI  - Segmentation and fusion on the midline: basibranchial homologies in cypriniform
      fishes.
AB  - The development and homologies of the median elements of the ventral hyoid and
      branchial arches of Cypriniformes have been unclear. We compared the
      developmental morphology of this region across five species (Cycleptus elongatus,
      Luxilus zonatus, Danio rerio, Devario auropurpureus, and Cobitis striata),
      representing three of five major clades of cypriniforms. The development of
      basibranchial 1 is similar in catostomids and cyprinids, where a single,
      elongate, basihyal + anterior copula divides into separate elements. A gap
      develops between the posterior end of the basihyal cartilage and the anterior
      copula in catostomids but in cyprinids (Luxiluszonatus, Danio rerio, and
      Devarioauropurpureus) there is little separation and the basihyal and
      basibranchial 1 may grow close together or retain a cartilaginous connection
      (Danio rerio, several outgroups). In loaches and Gyrinocheilus, the gap posterior
      to the basihyal has been alternately interpreted as either the absence or
      posterior displacement of basibranchial 1. Uniquely among examined species, in
      Cobitis striata, the basihyal cartilage and anterior copula form as separate
      cartilages and remain distinct throughout development with a prominent gap
      between the basihyal and most anterior basibranchial, which we interpret as loss
      of basibranchial 1. In the posterior region associated with branchial arches 4
      and 5, all examined species except Danio rerio, which has only a basibranchial 4
      cartilage, have separate basibranchial 4 and 5 cartilages in early ontogeny.
      Basibranchials 4 and 5 remain separate in Cycleptus elongatus, Devario
      auropurpurea, and Cobitis striata, but fuse in Luxilus zonatus to form a
      posterior copula. The orientation of basibranchial 4 and 5 cartilages in Cobitis
      striata is similar to catostomids and cyprinids. The most posterior median
      element in the branchial arches, the post-ceratobranchial cartilage, generally
      forms as a separate cartilage in catostomids but in Cobitis striata is connected
      with basibranchial 5 cartilage from earliest appearance.

PMID- 22460807
TI  - The effect of cold ischemic time on the immunohistochemical evaluation of
      estrogen receptor, progesterone receptor, and HER2 expression in invasive breast
      carcinoma.
AB  - The American Society of Clinical Oncology/College of American Pathologist
      (ASCO/CAP) guidelines on breast cancer currently recommend a cold ischemic time
      of <1 h, although data are limited. Breast resection specimens were subjected to
      variable cold ischemic time periods (0.5, 1, 2, 3, 4, 24, and 48 h) within the
      refrigerator and at room temperature. The study included 25 tumors, all of which
      had refrigerated samples. Non-refrigerated samples (samples at room temperature)
      were present on 23 cases. Hormone receptors were semi-quantitatively scored using
      the H-score method. Human epidermal growth factor receptor 2 gene ERBB2 (HER2)
      was scored using the ASCO/CAP guidelines. The results were compared with the core
      biopsy scores, which have negligible cold ischemic time period before fixation.
      Mild reduction in staining for hormone receptors was judged present if the H
      score on the resection specimen was between one-half and three-fourth of the H
      score at core biopsy. Significant reduction was judged present when the H-score
      on resection was less than one-half of the core biopsy H-score. Mild reduction in
      HER2 staining was judged present if there was one-step reduction; and significant
      reduction was judged present if there was two-step reduction in staining. A true
      reduction was judged present only when the reduction was consistently present for
      the increasing time interval. A focal reduction for a particular time sample was
      attributed to the heterogeneity of the tumor sample. Non-refrigerated samples are
      affected more by prolonged cold ischemic time than refrigerated samples. Cold
      ischemic time period of as short as one-half hour may occasionally impact the
      immunohistochemical (IHC) staining for progesterone receptor. Significant
      reduction in IHC staining for hormone receptors, and HER2, however, generally
      does not result until 4 h for refrigerated samples and 2 h for non-refrigerated
      samples. The ASCO/CAP guideline of cold ischemic time period of <1 h is a prudent
      guideline to follow.

PMID- 22460808
TI  - Role of HERG1 potassium channel in both malignant transformation and disease
      progression in head and neck carcinomas.
AB  - Evidence indicates that human ether a-go-go-related gene 1 (HERG1) voltage-gated
      potassium channels could represent new valuable membrane therapeutic targets and
      diagnostic/prognostic biomarkers in various cancers. This study is the first to
      investigate the expression pattern of HERG1 potassium channel subunit in both
      primary tumors and precancerous lesions to establish its clinical and biological
      role during the development and progression of head and neck squamous cell
      carcinomas. HERG1 protein expression was evaluated by immunohistochemistry in
      paraffin-embedded tissue specimens from 133 patients with
      laryngeal/hypopharyngeal squamous cell carcinomas and 75 patients with laryngeal
      dysplasia, and correlated with clinical data. Our findings demonstrate that HERG1
      is frequently aberrantly expressed in a high percentage of primary tumors (87%),
      whereas expression was negligible in both stromal cells and normal-adjacent
      epithelia. HERG1 expression increased during head and neck squamous cell
      carcinoma progression and was significantly associated with lymph node metastasis
      (P=0.04), advanced disease stages (P<0.001), regional tumor recurrence (P=0.004),
      distant metastasis (P=0.03) and reduced disease-specific survival (P=0.012, log
      rank test). HERG1-positive expression was also detected in 31 (41%) of 75
      laryngeal dysplasias. Interestingly, HERG1 expression increased with the grade of
      dysplasia; however, HERG1 expression but not histology correlated significantly
      with increased laryngeal cancer risk (P=0.007). In addition, functional studies
      in head and neck squamous cell carcinoma-derived cell lines further revealed that
      HERG1 expression promotes anchorage-dependent and -independent cell growth and
      invasive capability, although independently of its ion-conducting function. Our
      data demonstrate that HERG1 expression is a biologically and clinically relevant
      feature in head and neck squamous cell carcinoma progression and also during
      malignant transformation, and a promising candidate as cancer risk marker and
      therapeutic target for head and neck squamous cell carcinoma prevention and
      treatment.

PMID- 22460809
TI  - High expression of prostate-specific membrane antigen in the tumor-associated neo
      vasculature is associated with worse prognosis in squamous cell carcinoma of the
      oral cavity.
AB  - Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in
      prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors.
      Here, we determined the expression pattern of PSMA in the vasculature of oral
      squamous cell carcinoma. Using a previously validated antibody, PSMA staining
      distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a
      cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using
      immunohistochemistry and was correlated with clinicopathological features as well
      as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%)
      demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels
      and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of
      tumor-associated microvessels. High endothelial PSMA expression was associated
      with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained
      prognostic significance after adjusting for grade and stage in multivariate
      analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong
      association between endothelial PSMA and cancer cell-specific COX2 expression. In
      conclusion, we provide the first evidence for the prognostic significance of
      endothelial PSMA expression in oral squamous cell carcinoma and, suggest a
      potential interaction between arachidonic acid metabolites and endothelial PSMA
      expression in the tumor neo-vasculature.

PMID- 22460810
TI  - DOG1: a novel marker of salivary acinar and intercalated duct differentiation.
AB  - Anoctamin-1 (ANO1) (DOG1, TMEM16a) is a calcium-activated chloride channel
      initially described in gastrointestinal stromal tumors, but now known to be
      expressed in a variety of normal and tumor tissues including salivary tissue in
      murine models. We herein perform a comprehensive survey of DOG1 expression in 156
      cases containing non-neoplastic human salivary tissues and tumors. ANO1 mRNA
      levels were significantly higher (8-fold increase, P<0.0001) in normal parotid
      tissue (n=6) as compared with squamous mucosa (n=15). By immunohistochemistry,
      DOG1 showed a diffuse moderate (2+) apical membranous staining pattern in normal
      serous acini, 1+ apical membranous pattern in mucous acini, and variable 1-2+
      apical staining of distal intercalated ducts. Myoepithelial cells, striated and
      excretory ducts were invariably negative. All acinic cell carcinomas (n=28) were
      DOG1 positive demonstrating a complex mixture of intense (3+) apical membranous,
      cytoplasmic and complete membranous staining. Most ductal tumor types were
      negative or only showed a subset of positive cases. Within the biphasic tumor
      category, adenoid cystic carcinomas (18/24 cases) and epithelial-myoepithelial
      carcinomas (8/15 cases) were frequently positive, often showing a distinctive
      combined apical ductal and membranous/cytoplasmic myoepithelial staining profile.
      Thus, DOG1 staining is a marker of salivary acinar and to a lesser extent
      intercalated duct differentiation. Strong staining can be used to support the
      diagnosis of acinic cell carcinoma. DOG1 may also be a marker of a 'transformed'
      myoepithelial phenotype in a subset of biphasic salivary gland malignancies.

PMID- 22460811
TI  - Expression of thyroid transcription factor-1 in normal endometrium is associated
      with risk of endometrial cancer development.
AB  - Thyroid transcription factor-1 (TTF-1) is a DNA-binding protein that is mainly
      expressed in thyroid and lung tissue, but has also been found in gynecologic
      tissue. Recent studies have suggested that TTF-1 has tumor suppressor function in
      lung adenocarcinoma models. In the current study, we examined whether expression
      of TTF-1 in benign endometrium and endometrial hyperplasia might impact on the
      risk of developing endometrial cancer. Formalin-fixed paraffin-embedded
      endometrial tissues obtained from 535 cases were used to construct an endometrial
      tissue microarray. One hundred fifty of 207 patients had multiple serial
      endometrial specimens including 46 patients who progressed to endometrial cancer.
      The tissue microarray included a range of histopathologies including benign
      endometrium (n=231), simple hyperplasia (n=105), complex hyperplasia (n=36),
      simple atypical hyperplasia (n=10), complex atypical hyperplasia (n=44), and
      endometrial carcinoma (n=109). Expression of TTF-1 by immunohistochemistry in
      benign endometrium and endometrial hyperplasia was correlated with progression to
      cancer and clinical features known to be associated with increased risk of
      developing endometrial cancer. Carcinoma specimens showed a significantly greater
      expression of TTF-1 compared with benign endometrium and non-atypical hyperplasia
      (P=0.0007 and P=0.05). Presence of TTF-1 expression in benign endometrium was
      associated with a significantly decreased risk of cancer development (P=0.003,
      hazards ratio=0.104, 95% CI: 0.024-0.455). TTF-1 expression in hyperplasia did
      not significantly correlate with progression to cancer. The data from our study
      show that TTF-1 expression in normal endometrium is associated with a reduced
      risk of endometrial cancer development. This observation suggests that TTF-1
      might function as a tumor suppressor in endometrial tissue. TTF-1 expression in
      normal endometrium could potentially provide clinically useful information as a
      biomarker for the risk of endometrial cancer.

PMID- 22460812
TI  - Inflammation and preneoplastic lesions in benign prostate as risk factors for
      prostate cancer.
AB  - Benign changes ranging from atrophy and inflammation to high-grade prostatic
      intraepithelial neoplasia (HGPIN) are common findings on prostate core needle
      biopsies. Although atrophy and inflammation may be precursors of prostate cancer,
      only HGPIN is currently recommended to be included in surgical pathology reports.
      To determine whether these benign findings increase prostate cancer risk, we
      conducted a case-control study nested within a historical cohort of 6692 men with
      a benign prostate specimen collected between 1990 and 2002. The analytic sample
      included 574 case-control pairs comprised of cases diagnosed with prostate cancer
      a minimum of 1 year after cohort entry and controls matched to cases on date and
      age at cohort entry, race, and type of specimen. The initial benign specimen was
      reviewed for presence of HGPIN, atrophy (simple, lobular, and partial) and
      inflammation (glandular and/or stromal). HGPIN significantly increased risk for
      prostate cancer (odds ratio (OR)=2.00; 95% confidence interval (CI)=1.25-3.20).
      Inflammation within the stromal compartment was associated with decreased risk
      (OR=0.66; CI=0.52-0.84), and diffuse stromal inflammation of severe grade had the
      strongest inverse association with risk (OR=0.21; CI=0.07-0.62). In a model
      adjusted for prostate-specific antigen (PSA) level at cohort entry and
      inflammation, simple atrophy was associated with a 33% increased prostate cancer
      risk that was marginally significant (P=0.03). Clinicians should consider
      patterns and extent of inflammation when managing high-risk patients with
      negative biopsy results. Identifying benign inflammatory processes that underlie
      high PSA levels would help to reduce the number of unnecessary repeated prostate
      biopsies.

PMID- 22460813
TI  - Novel, gross chromosomal alterations involving PTEN cooperate with allelic loss
      in prostate cancer.
AB  - There is increasing evidence that multiple chromosomal rearrangements occur in
      prostate cancer. PTEN loss is considered to be a key event in prostate
      carcinogenesis but the mechanisms of loss remain to be fully elucidated. We
      hypothesised that gross rearrangements may exist that cause disruption of the
      PTEN gene in the absence of genomic deletion. We therefore designed a novel
      fluorescence in situ hybridisation (FISH) assay with probes overlying regions 3'
      and 5' of PTEN and a third probe overlying the gene. We aimed to identify both
      genomic deletions and gross rearrangements of PTEN that would be overlooked by
      previously reported single-probe FISH assays. We proceeded to evaluate a tissue
      microarray with radical prostatectomy and trans-urethral resection of the
      prostate specimens from 187 patients. We identified PTEN genomic loss in 45/150
      (30%) radical prostatectomy patients and 16/37 (43%) trans-urethral resection of
      the prostate patients. Importantly, our assay detected novel chromosomal
      alterations in the PTEN gene (characterised by splitting of FISH signals) in 13
      tumours (6.9% of all prostate cancers; 21% of PTEN-lost cancers). All PTEN
      rearranged tumours had genomic loss at the other allele and had no expression of
      PTEN by immunohistochemistry. PTEN-rearranged tumours were significantly more
      likely to have an underlying ERG rearrangement. Our assay differentiated loss of
      the probe overlying PTEN in isolation or in combination with either one of or
      both the probes overlying the 3' and 5' regions. This gave an indication of the
      size of genomic loss and we observed considerable inter-tumoural heterogeneity in
      the extent of genomic loss in PTEN-lost tumours. In summary, gross rearrangements
      of the PTEN locus occur in prostate cancer and can be detected by a 'break-apart'
      FISH assay. This observation could explain the absence of PTEN protein expression
      in a subgroup of tumours previously classified as having heterozygous genomic
      loss using single-probe traditional FISH assays.

PMID- 22460814
TI  - Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar
      cell lesions.
AB  - The phosphatidylinositol-3-kinase pathway is one of the most commonly mutated
      pathways in invasive breast carcinoma, with PIK3CA mutations in ~25% of invasive
      carcinomas, and AKT1 mutations in up to 5%. Ductal carcinoma in situ, and benign
      papillomas harbor similar mutations. However, activating point mutations in
      breast columnar cell lesions have been infrequently studied. Twenty-three breast
      resection specimens containing columnar cell lesions were identified; 14 with
      associated invasive carcinoma or carcinoma in situ. DNA extracts were prepared
      from formalin-fixed paraffin-embedded tissue and screened for a panel of point
      mutations (321 mutations in 30 genes) using a multiplex PCR panel with mass
      spectroscopy readout. PIK3CA mutations were identified in 13/24 columnar cell
      lesions (54%) and 3/8 invasive carcinomas (37%). The mutation status of columnar
      cell lesions and associated carcinoma was frequently discordant. Of the 14 cases,
      only 5 demonstrated the same genotype in matched samples of columnar cell lesions
      and carcinoma (4 wild type, 1 PIK3CA H1047R). Interestingly, five patients had
      mutations in columnar cell lesions with wild-type carcinoma; two patients had
      different point mutations in columnar cell lesions and carcinoma. Only three
      cases had wild-type columnar cell lesion and mutated carcinoma. The 50% PIK3CA
      mutation prevalence in columnar cell lesions is greater than reported in most
      studies of invasive breast cancer. Further, columnar cell lesions and carcinoma
      were frequently discordant for PIK3CA/AKT1 mutation status. These findings raise
      interesting questions about the role of PIK3CA/AKT pathway in breast
      carcinogenesis, and the biologic/precursor potential of columnar cell lesions.

PMID- 22460816
TI  - Re: Naunheim MR, Walcott BP, Nahed BV, et al. The quality of randomized
      controlled trial reporting in spine literature. Spine 2011;36:1326-30.

PMID- 22460818
TI  - Ecdysone-responsive transcription factors determine the expression region of
      target cuticular protein genes in the epidermis of Bombyx mori.
AB  - In the present study, we found that different ecdysone-responsive transcription
      factors were expressed differentially in different regions of the epidermis at
      around pupation. betaFTZ-F1 transcripts were strongly but E74A transcripts were
      barely observed in the thoracic region of the epidermis, and vice versa in the
      abdominal region. Transcripts of all the examined transcription factors were
      observed in wing disc. Transcript of a cuticular protein gene, BMWCP4, which does
      not have a betaFTZ-F1 binding site in the 2-kb upstream region, was not observed
      in the thoracic region of the epidermis. Transcript of BMWCP9, which does not
      have an E74 binding site in the 2-kb upstream region, was not observed in the
      abdominal region of the epidermis. BMWCP2 has all the transcription factor
      binding sites examined and was expressed in the thoracic and abdominal region of
      the epidermis. Thus, it is suggested that ecdysone-responsive transcription
      factors determined the space where the cuticular protein genes were expressed,
      which, in turn, determined the character of the cuticle that was characterized by
      the combination of cuticular proteins.

PMID- 22460819
TI  - A cellular network of dye-coupled glia associated with the embryonic central
      complex in the grasshopper Schistocerca gregaria.
AB  - The central complex of the grasshopper (Schistocerca gregaria) brain comprises a
      modular set of neuropils, which develops after mid-embryogenesis and is
      functional on hatching. Early in embryogenesis, Repo-positive glia cells are
      found intermingled among the commissures of the midbrain, but then redistribute
      as central complex modules become established and, by the end of embryogenesis,
      envelop all midbrain neuropils. The predominant glia associated with the central
      body during embryogenesis are glutamine synthetase-/Repo-positive astrocyte-like
      glia, which direct extensive processes (gliopodia) into and around midbrain
      neuropils. We used intracellular dye injection in brain slices to ascertain
      whether such glia are dye-coupled into a communicating cellular network during
      embryogenesis. Intracellular staining of individual cells located at any one of
      four sites around the central body revealed a population of dye-coupled cells
      whose number and spatial distribution were stereotypic for each site and
      comparable at both 70 and 100% of embryogenesis. Subsequent immunolabeling
      confirmed these dye-coupled cells to be astrocyte-like glia. The addition of n
      heptanol to the bathing saline prevented all dye coupling, consistent with gap
      junctions linking the glia surrounding the central body. Since dye coupling also
      occurred in the absence of direct intersomal contacts, it might additionally
      involve the extensive array of gliopodia, which develop after glia are arrayed
      around the central body. Collating the data from all injection sites suggests
      that the developing central body is surrounded by a network of dye-coupled glia,
      which we speculate may function as a positioning system for the developing
      neuropils of the central complex.

PMID- 22460820
TI  - Autologous transplantation of culture-born myofibroblasts into intact and injured
      rabbit ligaments.
AB  - PURPOSE: The myofibroblast, a contractile fibroblastic cell expressing alpha
      smooth muscle actin (alpha-SMA), has been reported to play a role in ligament
      healing. The aim of this study was to evaluate the feasibility of transplanting
      culture-derived myofibroblasts in injured rabbit medial collateral ligaments
      (MCL) and in intact anterior cruciate ligaments (ACL). METHODS: Fibroblasts
      isolated from the iliotibial band were cultured in the presence of transforming
      growth factor beta-1 (TGF-beta1) for five days and analysed for alpha-SMA
      expression. In a concentration of TGF-beta1 >= 10 ng/ml, the differentiation rate
      into myofibroblast was 90%. After labelling with PKH26, alpha-SMA -positive cells
      were transplanted in intact ACL and in injured MCL of ten rabbits. RESULTS:
      Survival of PKH-26+ cells was seen in all intact and damaged ligaments one day
      after injection. The density of PKH-26+ cells had decreased at seven days
      postinjection in both ligaments. Double-positive PKH-26+/alpha-SMA+ cells were
      only observed in injured MCL at seven days postinjection. Moreover, we found that
      genetically modified fibroblasts differentiate into myofibroblasts and can be
      transplanted into ligaments. CONCLUSIONS: Our data demonstrate that culture-born
      myofibroblasts survive and maintain alpha-SMA expression up to one week after
      transplantation. This study provides the first insight into the feasibility of
      transplanted mechanically active cells for ligament reconstruction.

PMID- 22460821
TI  - Initial Achilles tendon repair strength--synthesized biomechanical data from 196
      cadaver repairs.
AB  - PURPOSE: The study aim was to describe what kind of operative technique performs
      best with respect to initial strength after the surgical repair of acute Achilles
      tendon ruptures. METHODS: We performed a systematic search of the keywords
      "Achilles tendon AND (suture strength OR biomechanics) AND (cadaver NOT animal)"
      in the online databases PubMed, EMBASE, CINAHL, and the Cochrane Library. We
      included studies that employed open, mini-open, or percutaneous Achilles tendon
      repair in human cadavers, and assessed some measure of tensile strength as a
      primary outcome. RESULTS: Our search produced 11 relevant papers reporting
      results for Kessler, Bunnell, and Krackow sutures in open repair, as well as the
      Achillon device, the Ma-Griffith repair technique, the triple bundle technique
      and the "giftbox" technique. The weighted tensile strengths ranged from 81 to 453
      N (mean 222.7 N) with the Triple Bundle technique in combination with # 2
      Ethibond performing best with a mean of 453 N. CONCLUSIONS: Due to the small
      sample sizes, different study designs, and heterogeneity of strength measurement
      techniques, definite recommendations on surgical technique cannot be made but
      presented information might help in the decision making process for foot and
      ankle surgeons.

PMID- 22460822
TI  - Evidence of myocardial edema in patients with nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Nonischemic dilated cardiomyopathy (DCM) is associated with high
      mortality and morbidity. Cardiovascular magnetic resonance allows for the
      noninvasive assessment of function, morphology, and myocardial edema. Activation
      of inflammatory pathways may play an important role in the etiology of chronic
      DCM and may also be involved in the disease progression. HYPOTHESIS: The purpose
      of our study was to assess the incidence of myocardial edema as a marker for
      myocardial inflammation in patients with nonischemic DCM. METHODS: We examined 31
      consecutive patients ( mean age, 57 +/- 12 years) with idiopathic DCM. Results
      were compared with 39 controls matched for gender and age (mean age, 53 +/- 13
      years). Parameters of left ventricular function and volumes, and
      electrocardiogram-triggered, T2-weighted, fast spin echo triple inversion
      recovery sequences were applied in all patients and controls. Variables between
      patients and controls were compared using t tests for quantitative and chi2 tests
      for categorical variables. RESULTS: Ejection fraction (EF) was 40.3 +/- 7.8% in
      patients and 62.6 +/- 5.0% in controls (P < 0.0001). In T2-weighted images,
      patients with DCM had a significantly higher normalized global signal intensity
      ratio compared to controls (2.2 +/- 0.6 and 1.8 +/- 0.3, respectively, P =
      0.0006), consistent with global myocardial edema. There was a significant but
      moderate negative correlation between signal intensity ratio in T2-weighted
      images and EF (-0.39, P < 0.001). CONCLUSIONS: Evidence shows that myocardial
      edema is associated with idiopathic nonischemic DCM. Further studies are needed
      to assess the clinical and prognostic impact of these findings.

PMID- 22460823
TI  - Changes in the melanocortin receptors in the hypothalamus of a rat model of
      cancer cachexia.

PMID- 22460824
TI  - Treatment of odontogenic large cysts in haemophiliac patients.

PMID- 22460825
TI  - Pollen Typhae is a rapid hemostyptic.

PMID- 22460826
TI  - Conformational flexibility of a protein-carbohydrate complex and the structure
      and ordering of surrounding water.
AB  - Protein-carbohydrate non-covalent interactions are important to understand
      various biological processes in living organisms. One of the important issues in
      protein-carbohydrate binding is how the protein identifies the target
      carbohydrate and recognizes its conformational features. Surrounding water
      molecules are expected to play a critical role not only in mediating the
      recognition process but also in maintaining the structure of the complex. We
      carried out atomistic molecular dynamics (MD) simulations of an aqueous solution
      of the protein-carbohydrate complex formed between the hyaluronan binding domain
      (HABD) of the murine Cd44 protein and the octasaccharide hyaluronan (HA(8)). The
      conformational flexibilities of the protein and the carbohydrate, and the
      microscopic structure and ordering of water molecules around them in the
      complexed form have been explored. It is revealed that the formation of the
      complex is associated with significant immobilization of the monosaccharide units
      of the carbohydrate moiety that are involved in binding. Further, reduction in
      water densities around the binding residues of the two molecules in the complex
      with respect to their free forms clearly demonstrated that the recognition
      between the protein and the carbohydrate is facilitated by removal of a fraction
      of water molecules from regions around the binding domains.

PMID- 22460827
TI  - Safety and efficacy of linezolid in 16 infants and children in Japan.
AB  - Linezolid, an oxazolidinone antibiotic, exhibits a broad spectrum of activity
      against Gram-positive bacteria. It has been licensed for adult use in Japan since
      2006 for MRSA infections, and has also been used off-label for pediatric
      patients. At our university hospital, a total of 16 infants and children
      (including one non-Japanese Asian) were administered linezolid owing to infection
      with multidrug-resistant Gram-positive bacteria, after consent had been provided.
      All patients had severe underlying diseases or indications for surgery. Eighty
      eight percent of the causal microorganisms were methicillin-resistant
      Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative
      Staphylococcus and all were sensitive to linezolid. Linezolid was administered
      because the antecedent anti-MRSA medications were ineffective or contraindicated,
      or intravenous-to-oral switch therapy was requested owing to cardiac or
      orthopedic surgical-site infections. The median duration of administration was 13
      days (range 3-31 days). The overall efficacy was 91 % (10/11) in those for whom
      efficacy could be evaluated. Only two patients (both teen-aged) encountered
      linezolid-related adverse effects (13 %, 2/16). One patient showed elevation of
      liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase
      [ALT]), requiring that administration be withdrawn, but enzyme levels returned to
      normal after the patient had been switched to vancomycin. The other patient
      showed transiently decreased platelet counts. Linezolid is considered generally
      safe and effective for children in Japan, especially for those who cannot use
      other anti-MRSA medications or those who require oral antibiotics for infections
      with multidrug-resistant Gram-positive bacteria.

PMID- 22460828
TI  - Retrospective investigation of the clinical effects of tazobactam/piperacillin
      and sulbactam/ampicillin on aspiration pneumonia caused by Klebsiella pneumoniae.
AB  - Klebsiella pneumoniae is an important causative bacterium of aspiration pneumonia
      in many elderly patients. We retrospectively investigated the clinical effects of
      the early treatment of aspiration pneumonia and background factors in 24 patients
      from whom Klebsiella pneumoniae was isolated. Sulbactam/ampicillin (SBT/ABPC) was
      selected for early treatment in 12 of the 24 patients diagnosed with aspiration
      pneumonia, and tazobactam/piperacillin (TAZ/PIPC) was selected for the other
      patients. The effective rates and success rates of early treatment were
      significantly higher in the TAZ/PIPC group than in the SBT/ABPC group (p = 0.003
      and 0.027, respectively). Although no significant difference was noted because of
      the limited number of cases, the survival rates after 30 days were 91.7 and 58.3
      % in the TAZ/PIPC and SBT/ABPC groups, respectively. Several bacteria isolated
      with Klebsiella pneumoniae were resistant bacteria, such as methicillin-resistant
      Staphylococcus aureus or Pseudomonas aeruginosa, and no anaerobe or extended
      spectrum beta-lactamase-producing Klebsiella pneumoniae was isolated. Thirteen
      and 11 of the 24 cases were classified as healthcare-associated pneumonia (HCAP)
      and hospital-acquired pneumonia (HAP), respectively, with no case classified as
      community-acquired pneumonia (CAP). As population aging progresses, the frequency
      of aspiration pneumonia classified as HCAP will increase. To cover anaerobes, it
      is necessary to select antibacterial drugs, such as TAZ/PIPC, for early treatment
      in consideration of resistant gram-negative bacteria to improve the outcome, and
      not drugs with weak activity against these bacteria.

PMID- 22460829
TI  - Analysis of clinical features of non-HIV Pneumocystis jirovecii pneumonia.
AB  - Pneumocystis jirovecii pneumonia (PCP) is classified as PCP with human
      immunodeficiency virus (HIV) and non-HIV PCP, and the two forms differ in
      progression and prognosis. Although early treatment is necessary, the diagnosis
      of non-HIV PCP is often difficult because of the underlying diseases. However,
      the outcome with treatment delay remains unclear because there are no concrete
      data indicating a worsened clinical situation or increased complications related
      to delayed therapy initiation. We retrospectively examined patients with non-HIV
      PCP admitted to Tokyo Women's Medical University Hospital from November 2008 to
      October 2010. The relationship between intubation with mechanical ventilation
      (within 1 week after starting treatment) and treatment delay was investigated.
      Treatment delay was defined as the period, in days, from onset to therapy
      initiation. In total, 24 confirmed non-HIV PCP cases were included. Median
      treatment delay was 7 +/- 4.83 days (1-20 days). Twelve of 24 cases (50 %) were
      intubated, and 11 (45.8 %) died of their underlying diseases within 90 days.
      Treatment delay was more than 7 days in the intubation group, but was within 7
      days in 9 of 12 nonintubation cases. The difference in treatment delay was
      significant (p = 0.0071) between the intubation and nonintubation groups, but
      there were no significant differences in survival rate at 90 days or other
      findings. We conclude that starting treatment within 7 days after onset is
      important because intubation and mechanical ventilation may be avoided in many
      cases.

PMID- 22460830
TI  - A qualitative study of HIV testing and referral practices of private hospital
      doctors treating patients with TB in Chennai, India.
AB  - OBJECTIVE: In India, 50%-80% of patients with tuberculosis (TB) seek private
      care. This study set out to explore HIV testing and referral practices of private
      hospital doctors treating patients with TB. METHODS: Interviews were conducted
      with private hospital doctors (n = 15). Interviews covered HIV testing, linking
      HIV-positive patients with TB to HIV care, and coordination of care for co
      infected patients. RESULTS: Doctors did not routinely refer patients with TB to
      government HIV testing facilities as per national policy guidance. If deemed
      appropriate, then testing was conducted privately. Testing was more common when a
      facility guideline mandated testing or a public-private initiative for TB
      management was in place. Otherwise, testing was based on doctors' judgement.
      Patients accustomed to private care who could not afford treatment were
      reportedly reluctant to shift to public facilities. A lack of communication
      between public and private doctors was found to undermine co-management.
      CONCLUSIONS: In this sample, private provider practices were influenced by both
      the social and the health systems contexts in which they operated. An
      understanding of patient perceptions of HIV, private doctors concerns for
      retaining patients, and the contrasting philosophies of private medicine versus
      public health objectives was found to be critical to explain HIV testing and
      referral behaviours. The government has proposed to scale up HIV testing and
      treatment among patients with TB, yet operationalising this will require
      engagement with the realities of a large, diverse private sector. It will also
      require considering what role government policies can have on shaping private
      practice and how to potentially integrate public and private care.

PMID- 22460831
TI  - Glucose reintroduction triggers the activation of Nrf2 during experimental
      ischemia reperfusion.
AB  - Reperfusion results in a rapid reintroduction of oxygen, glucose, and other
      restricted components to an ischemic tissue. It brings with it not only the
      necessary components for cell survival but also a burst of oxidative stress and
      cellular damage. In this study, our primary aims were to investigate glucose as a
      determining factor for the activation of the transcription factor NF-E2-related
      factor 2 (Nrf2) upon reperfusion and the expression of downstream anti-oxidant
      NADPH-dependent reductases. Exposure of renal epithelial HK-2 cells to oxygen and
      glucose reintroduction after depletion resulted in an increase in nuclear
      translocation of Nrf2 protein in a manner dependent upon glucose. This activation
      and the induction of the Nrf2-dependent gene NAD(P)H dehydrogenase, quinone 1
      (NQO1) was observed to be maximum at a concentration of 5 mM glucose. Microarray
      analysis of mRNA from siRNA targeted cells under these conditions revealed the
      Nrf2-dependent expression of NADPH-dependent reductase enzymes NQO1, Aldo-keto
      reductase family 1, members C1-3 and dehydrogenase/reductase (SDR family) member
      2 (DHRS2), all genes demonstrated to protect against oxidative stress-mediated
      cellular injury. In addition, NQO1 and DHRS2 mRNA levels were specifically
      upregulated on glucose reintroduction and were also increased in an in vivo
      ischemia reperfusion injury model of murine renal pedicle clamping. In
      conclusion, we demonstrate that glucose reintroduction after depletion activates
      Nrf2 and Nrf2 regulated NADPH-dependent reductase expression. We suggest these
      findings represent a previously unreported mechanism for the activation of Nrf2
      as a cytoprotective pathway in IRI.

PMID- 22460832
TI  - RAF-kinase inhibitor protein (RKIP) downregulation in esophageal cancer and its
      metastases.
AB  - Raf kinase inhibitor protein (RKIP) is an inhibitor of Raf-mediated activation of
      mitogen-activated protein (MAP) kinase (MEK)-MAP kinase and is considered as an
      important tumor suppressor. RKIP-expression was investigated retrospectively in
      321 esophageal cancers [179 adenocarcinomas (ACs), 142 squamous cell carcinomas
      (SCCs)]. RKIP-expression was further investigated in 41 precursor lesions
      consisting of 14 cases of non-dysplastic Barrett's mucosa, 5 low grade dysplasias
      (LGD), and 12 high grade dysplasias (HGD) as well as, 4 cases with low grade and
      6 cases with high-grade squamous cell dysplasia. Corresponding lymph node
      metastases were investigated in 140 patients, distant metastases in 29, and local
      recurrences in 12. High RKIP-expression was significantly more common in
      Barrett's mucosa without dysplasia and in LGD compared to HGD (p = 0.047, chi(2)
      test) and invasive AC (p < 0.001, chi(2) test). In 187 primary esophageal cancers
      (58.3 %) RKIP was downregulated (AC: 51.4 %; SCC: 66.9 %). RKIP status of primary
      tumors influenced RKIP expression in corresponding lymph node and distant
      metastases (p < 0.05, linear regression). Downregulation of RKIP was associated
      with shorter overall survival (OS) and disease free survival (DFS) in all tumors
      (p <= 0.05, Cox regression). In AC, downregulation of RKIP was an independent
      prognostic factor for OS and DFS (p <= 0.05, Cox regression), while in SCC it
      reached significance only in univariate analysis (p <= 0.05, log-rank test). In
      conclusion, downregulation of RKIP is associated with shorter survival in
      esophageal cancers, and RKIP status of tumor cells seems to be preserved at the
      formation of metastases. Inhibition of RKIP-downregulation might reduce the
      ability of esophageal cancers to establish disseminated disease.

PMID- 22460833
TI  - Etodolac, a cyclooxygenase-2 inhibitor, attenuates paclitaxel-induced peripheral
      neuropathy in a mouse model of mechanical allodynia.
AB  - The effect of the cyclooxygenase-2 (COX-2) inhibitor etodolac on the mechanical
      allodynia induced by paclitaxel was investigated in mice and compared with the
      effects of the nonselective COX inhibitors indomethacin and diclofenac, the
      selective COX-2 inhibitor celecoxib, the calcium channel alpha(2)delta subunit
      inhibitor pregabalin, the sodium channel blocker mexiletine, and the serotonin
      norepinephrine reuptake inhibitor duloxetine. The decrease in the paw-withdrawal
      threshold induced by paclitaxel was reversed by oral administration of etodolac
      at 10 mg/kg but was not affected by indomethacin, diclofenac, or celecoxib. The
      antiallodynic effect of etodolac gradually increased during repeated
      administration, and after 2 weeks the paw-withdrawal threshold at the
      preadministration point was significantly increased. Pregabalin, duloxetine, and
      mexiletine also showed an antiallodynic effect in this model. Whereas pregabalin
      had a preadministration effect similar to that of etodolac during repeated
      administration, mexiletine or duloxetine had no such effect. There was almost no
      difference in the distribution of etodolac and diclofenac in nervous tissue,
      indicating that COX inhibition is unlikely to be involved in the antiallodynic
      effect of etodolac. Etodolac did not show a neuroprotective effect against
      morphological transformations such as the axonal degeneration induced by
      paclitaxel. Instead, etodolac probably acts at the level of functional changes
      accompanying paclitaxel treatment, such as alterations in the activation state of
      components of the pain transmission pathway. Our findings suggest that etodolac
      attenuates paclitaxel-induced peripheral neuropathy by a COX-independent pathway
      and that it might be useful for the treatment of paclitaxel-induced peripheral
      neuropathy.

PMID- 22460834
TI  - Coexpression of Bcl-2 with epithelial-mesenchymal transition regulators is a
      prognostic indicator in hepatocellular carcinoma.
AB  - The anti-apoptosis factor Bcl-2 is known to contribute to tumorigenesis and
      metastasis. Epithelial-mesenchymal transition (EMT) may also participate in tumor
      invasion and metastasis. This study investigated the relationship between
      coexpression profiles of Bcl-2 and EMT regulators in hepatocellular carcinoma
      (HCC) tumor samples and clinical outcome. The nuclear (Nu) and cytoplasmic (Cyt)
      expression of Bcl-2 and the EMT regulators Twist-1, Twist-2, and Snail were
      determined by immunohistochemical staining in tumor tissue isolated from 97 HCC
      patients. The clinical prognostic values of both individual protein expression
      and various expression combinations were investigated using univariate and
      multivariate survival analysis. Results showed that patients with nuclear
      expression of Bcl-2 had worse clinical outcomes than patients exhibiting
      cytoplasmic expression. Overall survival was significantly shorter in HCC
      patients individually expressing Bcl-2-Nu, Twist-1-Nu, Twist-1-Cyt, and Snail
      (all P<0.05). Patients coexpressing Bcl-2-Nu with Twist-1-Nu, Twist-1-Cyt, Twist
      2, or Snail had even worse prognoses than those expressing no biomarker or any
      one biomarker alone (all P<0.05). Multivariate analysis showed that HCC patients
      coexpressing Bcl-2-Nu with Twist-1-Cyt had the worst prognosis. This study
      provides clinical evidence that nuclear expression of Bcl-2 combined with
      cytoplasmic expression of Twist-1 is a predictor of very poor prognosis in HCC.
      Coexpression profiles of Bcl-2 and EMT regulators might aid in the selection of
      the most efficacious therapy for patients with HCC.

PMID- 22460835
TI  - Melanoma with unknown primary: report and analysis of 24 patients.
AB  - In the literature, there are some papers reporting on patients with metastatic
      melanoma from an unknown primary lesion (MUP). The pathogenesis of this
      phenomenon and the prognosis of these patients are still debatable. Therefore, we
      reviewed our casistics on MUP patients. We identified 24 MUP patients out of all
      patients registered into a melanoma database from June 1996 to June 2011. The
      incidence was 1.4%. We compared the survival rate of all patients with MUP stage
      III-IV with all patients with metastatic melanoma known primary (MMKP) stage III
      IV observing a clear survival improvement for MUP patients in front of MMKP
      patients (p<0.01). In a second instance, we compared stage III MUP patients with
      only lymph nodal involvement with stage III MMKP patients with only lymph nodal
      involvement, and again we found statistically significant better survival for MUP
      patients (p<0.05). In this retrospective study, the number of lymph nodes
      involved (p=0.8), the sex (p=0.9), and S100 value (p=0.2) were not statistically
      relevant for prognosis. The better prognosis for these patients is very similar
      to better survival rate for metastatic melanoma patients and vitiligo. This
      correlation may be in accord with the hypothesis of a regression of primary
      lesion by immunological system of the host and also the median age of patients at
      the time of diagnosis, commonly older than melanoma patients, may correspond to a
      long period of immunological interferences between the host and the melanoma
      disease.

PMID- 22460836
TI  - Pretreatment serum C-reactive protein level predicts poor prognosis in patients
      with hepatocellular carcinoma.
AB  - C-reactive protein (CRP) is known to be associated with poor prognosis in
      patients with various malignancies. We investigated the relationship between the
      pretreatment serum CRP level and survival in patients with hepatocellular
      carcinoma (HCC) in various stages of the disease. A cohort of 133 patients with
      newly diagnosed HCC was prospectively evaluated. The patients were divided into
      two groups: high-CRP group (n=27) with the pretreatment serum CRP level?1.0 mg/dl
      and low-CRP group (n=106) with the CRP level<1.0 mg/dl. They were followed 22
      months in average (1-69 months) and clinicopathological variables, and overall
      survivals between the two groups were compared at the end of the follow-up
      period. There was a significant difference between the two groups in aspartate
      aminotransferase, alanine aminotransferase, total serum bilirubin, albumin, alpha
      fetoprotein level, maximal tumor diameter, frequency of vascular invasion and
      extrahepatic metastases. Patients in the high-CRP group had higher Child-Pugh
      scores, higher Cancer of the Liver Italian Program scores and higher Japan
      Integrated Staging scores than patients in the low-CRP group. The overall
      survival rates in the high-CRP group were significantly lower than those in the
      low-CRP group. Survival rates were similar in tumor stage and liver function
      matched patients. On multivariate analysis, pretreatment serum CRP level was
      independently associated with overall survival. Our results demonstrate that the
      pretreatment serum CRP level is associated with tumor progression and reduced
      liver function and is an independent poor prognostic marker in patients with HCC.

PMID- 22460838
TI  - Development and preparation of lead-containing paint films and diagnostic test
      materials.
AB  - Lead in paint continues to be a threat to children's health in cities across the
      United States, which means there is an ongoing need for testing and analysis of
      paint. This ongoing analytical effort and especially development of new methods
      continue to drive the need for diagnostic testing materials that provide the
      analytical challenges of real-world paints. To this end, 31 different types of
      paint test materials were developed and prepared. Preparation of the materials
      included development of lead-containing paint films yielding an overall relative
      standard error for one individual test sample being less than 10%. The 31
      diagnostic test materials prepared with these paint films included two lead
      pigments; lead concentrations from nominally 0 to 2.0 mg lead/cm(2) (0 to 5% lead
      by weight); overlayers of both "lead-free," oil-based and water-based paints; Al,
      Ba, and Mg as potential chemical interferents; red and black potential color
      interferents; and substrates of wood, metal, masonry, and plaster. These
      materials challenge each step in method development and evaluation, including
      paint sample collection and preparation, lead extraction, and measurement of
      solubilized lead. When the materials were used to test performance of a new lead
      in-paint testing method based on extraction using a rotor/stator method and
      measurement using turbidimetry, the results agreed to within +/-20% of the
      expected lead values for 30 out of 31 of the diagnostic test materials, thereby
      demonstrating their levels of quality and utility.

PMID- 22460839
TI  - From the Editor-in-Chief.

PMID- 22460837
TI  - Comparative efficacy of vascular endothelial growth factor (VEGF) tyrosine kinase
      inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor as second-line
      therapy in patients with metastatic renal cell carcinoma after the failure of
      first-line VEGF TKI.
AB  - Sequential therapy is a standard strategy used to overcome the limitations of
      targeted agents in metastatic renal cell carcinoma. It remains unclear whether a
      mammalian target of rapamycin (mTOR) inhibitor is a more effective second-line
      therapy after first-line vascular endothelial growth factor tyrosine kinase
      inhibitor (VEGF TKI) has failed than the alternative, VEGF TKI. A clinical
      database was used to identify all patients with renal cell carcinoma who failed
      at first-line VEGF TKI and then treated with second-line VEGF TKI or mTOR
      inhibitors in the Asan Medical Center. Patient medical characteristics,
      radiological response and survival status were assessed. Of the 83 patients who
      met the inclusion criteria, 41 received second-line VEGF TKI [sunitinib (n = 16)
      and sorafenib (n = 25)] and 42 were treated with mTOR inhibitors [temsirolimus (n
      = 11) and everolimus (n = 31)]. After a median follow-up duration of 23.9 months
      (95 % CI, 17.8-30.0), progression-free survival was 3.0 months for both groups
      [hazard ratio (HR, VEGF TKI vs. mTOR inhibitor) = 0.97, 95 % CI 0.59-1.62, P =
      0.92]. Overall survival was 10.6 months for the VEGF TKI group and 8.2 months for
      the mTOR inhibitor group (HR = 0.98, 95 % CI 0.57-1.68, P = 0.94). The two groups
      did not differ significantly in terms of disease control rate (51 % for VEGF TKI
      and 59 % for mTOR inhibitor, P = 0.75). Second-line VEGF TKI seems to be as
      effective as mTOR inhibitors and may be a viable option as a second-line agent
      after first-line anti-VEGF agents have failed.

PMID- 22460840
TI  - Epidemiology of osteoporosis.
AB  - Osteoporosis is defined as a reduction in bone mass and disruption of bone
      architecture, resulting in reduced bone strength and increase of bone fractures
      and it is responsible for more than 1.5 million fractures annually, including
      300,000 hip fractures, approximately 700,000 vertebral fractures, 250,000 wrist
      fractures, and more than 300,000 fractures at other sites. The lifetime risk for
      any fragility fractures in Caucasian women at age 50 years approaches 40% and 13%
      in men. During childhood and adolescence there is a rapid linear and appositional
      skeletal growth with a peak bone mass attained during the third decade of life.
      During adult life the mechanical integrity of the skeleton is maintained by the
      process of bone remodeling, in which old bone is removed by osteoclasts and
      subsequently replaced by new bone, formed by osteoblasts. In recent years, we
      have come to appreciate that the close association between bone and vasculature
      plays a pivotal role in the regulation of bone remodeling and fracture repair.
      Vitamin D, OPG/RANK/ RANK-L system, Matrix Gla-proteins (Mgp) and Fetuin
      A/calcium phosphate mineral phase complex play an important role in the
      regulation of bone homeostasis and vascular calcifications. A greater
      understanding of the biological linkages may lead to new dual-purpose therapies
      that may ultimately prevent the adverse outcomes of osteoporosis and
      atherosclerosis.

PMID- 22460841
TI  - Osteoporosis and cardiovascular diseases' cosegregation: epidemiological
      features.
AB  - Life expectancy in Italy is estimated to rise to 77.9 and 84.4 years in next
      years. Increased life expectancy is associated with a greater frailty of elderly
      people and an increased prevalence of chronic and degenerative illnesses such as
      cardiovascular diseases and osteoporosis. The impact of osteoporotic hip
      fractures in Italy is very similar to that of acute myocardial infarction (AMI),
      and there is a need for further epidemiological investigations concerning both
      the pathologies, as well as for a better understanding of possible mechanisms of
      their cosegregation. Actually, calcium metabolism is involved both in the
      development of osteoporosis and in the raise of cardiovascular risk. We have
      reviewed the most recent publications concerning epidemiological trends of both
      osteoporosis and acute myocardial infarction (AMI), and also the trials
      addressing cosegregation of these pathologies. According to the publications
      examined, in the Italian population (both >= 45 and > 65 years old), the number
      of hospitalizations following hip fracture and AMI are comparable. Both hip
      fractures and cardiovascular diseases represent in Italy a serious medical
      problem and a leading health cost driver, according to what has already been
      reported for many other Countries in the industrialized world, thus requiring a
      global clinical approach. Low calcium intake could represent one of the possible
      pathogenic paths underlining the association between hypertension and
      osteoporosis. Low calcium serum levels has been proved to enhance PTH and vitamin
      D3 production, which result in a remarkable lypogenesis performed by adypocites
      and switch on mechanisms leading to the raise of blood systolic pressure, the
      development of atherosclerotic plaques and cardiovascular events. Although many
      trials have suggested that bone mineral density may be included in the list of
      cardiovascular risk factors, more studies are needed in order to deeply
      investigate the causal relationships between calcium metabolism and
      cardiovascular diseases.

PMID- 22460843
TI  - Osteoporosis and cardiovascular disease: lessons from chronic kidney disease.
AB  - Osteoporosis is a common complication of chronic kidney disease (CKD), and the
      latter is a major risk factor for cardiovascular mortality. Recent studies have
      elucidated some of the mechanisms by which CKD is a cardiovascular risk, and they
      relate to osteoporosis. Thus, the mechanisms of CKD induced cardiovascular risk
      provide valuable insight into the relationship between cardiovascular disease and
      osteoporosis, and they are reviewed here. Observational studies have determined
      hyperphosphatemia to be a cardiovascular risk factor in chronic kidney disease.
      Mechanistic studies have elucidated that hyperphosphatemia is a direct stimulus
      to vascular calcification, which is one cause of morbid cardiovascular events
      contributing to the excess mortality of chronic kidney disease. Hyperphosphatemia
      in chronic kidney is due to failure of excretion by the kidneys and excess bone
      resorption. It stimulates vascular cells to mineralize atherosclerotic plaques
      through osteoblastic processes. Hyperphosphatemia in chronic kidney disease is a
      distinct syndrome characterized by disordered skeletal remodeling, heterotopic
      mineralization and cardiovascular morbidity. The heterotopic mineralization
      stimulated by CKD is relevant to osteoporosis.

PMID- 22460844
TI  - Cosegregation of cardiovascular diseases and osteoporosis: instrumental
      diagnosis.
AB  - Both atherosclerosis and osteoporosis are responsible for significant morbidity
      and mortality, are independent predictors of cardiovascular disease (CVD) events,
      and may share common regulatory mechanisms as well as histopathology. Abdominal
      aortic calcification (AAC), an indication of atherosclerosis, is significantly
      associated with both cardiovascular heart disease and stroke. The increased risk
      of cardiovascular disease mortality associated with moderate to severe AAC is
      similar to the increased risk of hip fracture in the presence of a moderate to
      severe vertebral fracture. A negative association between bone mineral density
      (BMD) and AAC severity has been also demonstrated.Several non-invasive methods
      are available to investigate the presence and the severity of osteoporosis. With
      some of these is possible to measure aortic calcification and bone mass in the
      same exam. A new method for the evaluation of aorta calcification by dual X-Ray
      absorptiometry (DXA) has been recently suggested: the Instant Vertebral
      Assessment (IVA), which offers the possibility to obtain in the same scan an
      assessment of vertebral fracture and AAC. Therefore, a single IVA exam could
      assist in stratifying patients into high and low risk groups for two highly
      prevalent and significant health care problems.

PMID- 22460842
TI  - The link between osteoporosis and cardiovascular disease.
AB  - Cardiovascular disease (CVD) and osteoporosis are common age-related conditions
      associated with significant morbidity, mortality, and disability.Traditionally,
      these two conditions were considered unrelated and their coexistence was
      attributed to independent age-related processes. However, an increasing body of
      biological and epidemiological evidence has provided support for a link between
      the two conditions that cannot be explained by age alone. Several hypotheses have
      been proposed to explain the link between osteoporosis and CVD including: 1)
      shared risk factors, 2) common pathophysiological mechanisms, 3) common genetic
      factors, or 4) a causal association.This review highlights the epidemiologic
      literature on the association of bone density with cardiovascular mortality,
      cardiovascular morbidity, and subclinical measures of atherosclerosis. It also
      summarizes the different potential mechanisms involved in the link between
      osteoporosis and CVD.

PMID- 22460845
TI  - Therapeutic perspectives.
AB  - Osteoporosis and atherosclerosis are linked by biological association. This
      encourages the search for therapeutic strategies having both cardiovascular and
      skeletal beneficial effects. Among drugs that may concordantly enhance bone
      density and reduce the progression of atherosclerosis we can include
      bisphosphonates (BP), statins, beta -blockers, and possibly anti-RANKL
      antibodies. Available data come from experimental animals and human studies. All
      these treatments however lack controlled clinical studies designed to demonstrate
      dual-action effects.

PMID- 22460846
TI  - Molecular biology of bone remodelling.
AB  - Bone remodelling is an active and dynamic process that relies on the correct
      balance between bone resorption by osteoclasts and bone deposition by
      osteoblasts. Moreover, these two functions must be tightly coupled not only
      quantitatively, but also in time and space. When the coupling is lost, the
      correct bone mass could be compromised, leading to several skeletal pathologies.
      Indeed, bone loss and osteoporosis are the result of an increased osteoclast
      function and/or a reduced osteoblast activity. In contrast, other pathologies are
      related to osteoclast failure to resorbe bone, such as osteopetrosis, a rare
      genetic disorder characterized by an increased bone mass and also linked to an
      impairment of bone marrow functions. Starting from these assumptions, it is
      necessary to more deeply understand the molecular mechanisms regulating bone cell
      functions. Indeed, recent studies evidenced a complex interplay between the
      immune and skeletal systems, which share several regulatory molecules including
      cytokines, receptors and transcription factors. These data allowed to more deeply
      understand the mechanisms underlying bone mass regulation and could open new
      avenue to identify target molecules for alterantive therapies more efficacious
      against bone diseases.

PMID- 22460847
TI  - Molecular biology of atherosclerosis.
AB  - The traditional view of atherosclerosis as a pathological lipid deposition within
      the artery wall has been redefined by a more complex concept of an ongoing
      inflammatory disease.The atherosclerotic process is initiated when cardiovascular
      risk factors, through a chemical, mechanical or immunological insult, activate
      and/or injury the endothelium, thus contributing to endothelial dysfunction and
      fragmentation. This triggers a cascade of inflammatory reactions, in which
      monocytes, macrophages, T lymphocytes, vascular smooth muscle cells actively
      participate. Particularly, atherosclerotic lesions have been seen to have
      increased expression of T helper-1 cells together with increased levels of the T
      helper-1 related pro-inflammatory cytokines. Along with pro-inflammatory
      cytokines, other molecular factors involved in atherosclerosis appearance,
      progression and complication include chemokines, growth factors, vasoactive
      substances, enzymes, apoptosis signals and many others. Many of these molecular
      factors are both involved as possible markers of the atherosclerotic disease
      activity and burden, but may also play a crucial role in the pathogenesis of the
      disease. In recent years, the discovery of progenitor cells of myeloid origin has
      offered the prospect of merging the most recent theories on the pathogenesis of
      atherosclerosis with the evolving concept of a role of these progenitor cells in
      the repair of the injured vessel wall and the neovascularisation of ischemic
      tissues. This review summarizes current knowledge about the biology of
      atherosclerosis with emphasis on the mechanisms of endothelial damage and repair
      and on the concept that the turnover and replacement of endothelial cells is a
      major determinant in the maintenance of vascular integrity.

PMID- 22460848
TI  - Genetics of cardiovascular disease.
AB  - Linkage studies and genome-wide linkage analyses, which use polymorphic DNA
      markers throughout the genome, provide a useful method for identifying genes
      related to cardiovascular disease (CVD). Many genome-wide linkage studies have
      contributed to identify quantitative genetic loci influencing variables involved
      in the pathogenesis of CVD.Meta-analyses of genetic studies provide the measure
      of association studies, so contributing to identify candidate genes which might
      influence the susceptibility to the disease. Really, candidate genes have been
      investigated, in relation to lipid metabolism (APOE), fibrinolytic proteins (PAI
      1), renin-angiotensyn system (ACE) and homocysteine metabolism (MTHFR). Recently,
      genome-wide panels of common single nucleotide polymorphisms (SNPs), based on the
      use of SNPs spread throughout the genome, are also becoming available. This
      approach contributes to finely investigate the gene-gene and gene-environment
      interactions in CVD, and to look for the involvement of genetic polymorphisms in
      drug response.

PMID- 22460849
TI  - Soluble molecules and bone metabolism in multiple myeloma: a review.
AB  - Bone metabolism and turnover are strongly altered in multiple myeloma, as a
      consequence of the proliferation of malignant cells resembling plasmacells in the
      bone marrow. By both direct or indirect secretion of several molecules, and cell
      to-cell interactions, multiple myeloma cells lead to severe and disabling
      skeletal alterations, such as osteolytic lesions, pathologic fractures, and
      osteoporosis. In this review, we summarize the studies concerning the soluble
      molecules which are supposed to have a role in this pathological process. We then
      consider the substances that, either in serum or urine specimens, can be dosed in
      the affected patients, thus giving an indirect measure of their altered bone
      turnover. In the last part of our review, we discuss the potential action of the
      new anti-myeloma drug bortezomib (Velcade((r)), Janssen-Cilag), in opposing and
      maybe reverting, through a possible direct "proosteoblastic" effect, the deranged
      bone turnover which characterizes this disabling and unavoidably deathly disease.

PMID- 22460851
TI  - Electrical velocimetry as a tool for measuring cardiac output in small infants
      after heart surgery.
AB  - PURPOSE: Cardiac output (CO), the product of stroke volume (SV) and heart rate,
      is essential to guarantee organ perfusion, especially in the intensive care
      setting. As invasive measurement of CO bears the risk of complications there is a
      need for non-invasive alternatives. We investigated if electrical velocimetry
      (EV) and transthoracic Doppler (Doppler-TTE) are interchangeable for the non
      invasive measurement of SV and able to reflect the post-surgical SV/CO trend.
      METHODS: Comparison of SV measurements by EV and Doppler-TTE was performed in 24
      newborns after switch operation (n = 240 measurements). Three subgroups of
      measurements (=periods) were created according to the patients' status in the
      course of post-surgical CO recovery. RESULTS: Bland-Altman analysis found
      acceptable bias and limits of agreement for the interchangeability of the two
      methods. Mean overall SV was 3.7 ml with a mean overall bias of 0.28 ml (=7.6 %).
      The mean percentage error of 29 % was acceptable according to the method of
      Critchley and Critchley. Overall precision expressed by the coefficient of
      variation (CV) was 6.6 % for SV(TTE) and 4.4 % for SV(EV). SV(TTE) and SV(EV)
      medians in the three periods were significantly different and documented the post
      surgical CO trend. CONCLUSIONS: EV and Doppler-TTE are interchangeable for
      estimating SV. EV has the advantages of easy handling and allows continuous
      measurement.

PMID- 22460852
TI  - Ethical and practical considerations concerning perimortem sperm procurement in a
      severe neurologically damaged patient and the apparent discrepancy in validation
      of proxy consent in various postmortem procedures.
AB  - INTRODUCTION: Although sperm procurement and preservation has been become
      commonplace in situations in which infertility can be easily foreseen, peri- or
      postmortem sperm procurement for reproductive use in unexpected coma or death is
      not generally accepted. There are no laws and regulations for this kind of
      intervention in all countries and they may also differ from country to country.
      Intensive care specialists can be confronted with a request for peri- or
      postmortem sperm procurement, while not being aware of the country-specific
      provisions. CASE DESCRIPTION: A young male patient who suffered 17 L blood loss
      and half an hour of cardiopulmonary resuscitation was admitted to a university
      hospital for an ill-understood unstoppable abdominal bleed. After rapid
      deterioration of the neurological situation, due to severe post-anoxic damage,
      the decision was made to withdraw life-sustaining treatment. At that moment the
      partner of the patient asked for perimortem sperm procurement, which was denied,
      on the basis of the ethical reasoning that consent of the man involved was
      lacking. Retrospectively the decision was right according to Dutch regulations;
      however, with more time for elaborate ethical reasoning, the decision outcome,
      without the awareness of an existing prohibition, also could have been different.
      CONCLUSIONS: Guidelines and laws for peri- or postmortem sperm procurement differ
      from country to country, so any intensive care specialist should have knowledge
      from the latest legislation for this specific subject in his/her country. An
      overview is provided. A decision based on ethical reasoning may appear
      satisfying, but can unfortunately be in full contrast with the existing laws.

PMID- 22460853
TI  - Surviving life-threatening MDMA (3,4-methylenedioxymethamphetamine, ecstasy)
      toxicity caused by ritonavir (RTV).

PMID- 22460854
TI  - Safety and efficacy of a fully closed-loop control ventilation (IntelliVent
      ASV(r)) in sedated ICU patients with acute respiratory failure: a prospective
      randomized crossover study.
AB  - PURPOSE: IntelliVent-ASV((r)) is a development of adaptive support ventilation
      (ASV) that automatically adjusts ventilation and oxygenation parameters. This
      study assessed the safety and efficacy of IntelliVent-ASV((r)) in sedated
      intensive care unit (ICU) patients with acute respiratory failure. METHODS: This
      prospective randomized crossover comparative study was conducted in a 12-bed ICU
      in a general hospital. Two periods of 2 h of ventilation in randomly applied ASV
      or IntelliVent-ASV((r)) were compared in 50 sedated, passively ventilated
      patients. Tidal volume (V(T)), respiratory rate (RR), inspiratory pressure
      (P(INSP)), SpO(2) and E(T)CO(2) were continuously monitored and recorded breath
      by breath. Mean values over the 2-h period were calculated. Respiratory
      mechanics, plateau pressure (P(PLAT)) and blood gas exchanges were measured at
      the end of each period. RESULTS: There was no safety issue requiring premature
      interruption of IntelliVent-ASV((r)). Minute ventilation (MV) and V(T) decreased
      from 7.6 (6.5-9.5) to 6.8 (6.0-8.0) L/min (p < 0.001) and from 8.3 (7.8-9.0) to
      8.1 (7.7-8.6) mL/kg PBW (p = 0.003) during IntelliVent-ASV((r)) as compared to
      ASV. P(PLAT) and FiO(2) decreased from 24 (20-29) to 20 (19-25) cmH(2)O (p =
      0.005) and from 40 (30-50) to 30 (30-39) % (p < 0.001) during IntelliVent
      ASV((r)) as compared to ASV. RR, P(INSP), and PEEP decreased as well during
      IntelliVent-ASV((r)) as compared to ASV. Respiratory mechanics, pH, PaO(2) and
      PaO(2)/FiO(2) ratio were not different but PaCO(2) was slightly higher during
      IntelliVent-ASV((r)) as compared to ASV. CONCLUSIONS: In passive patients with
      acute respiratory failure, IntelliVent-ASV((r)) was safe and able to ventilate
      patients with less pressure, volume and FiO(2) while producing the same results
      in terms of oxygenation.

PMID- 22460856
TI  - Subgross breast pathology in the twenty-first century.
AB  - Subgross studies on breast morphology in cleared thick sections are informative,
      but lengthy protocols could clash with diagnostic timescales and interfere with
      immunohistochemistry (IHC) or molecular analysis. We sought to speed up staining
      and tissue clearing to improve compatibility with diagnostic needs without
      detriment to histology or other assays. Thick sections (2-3 mm) of normal human
      breast tissue and whole mouse mammary glands were stained with alum-carmine,
      aceto-carmine, Harris's haematoxylin, cresyl violet, neutral red, thionin, 4',6
      diamidino-2-phenylindole (DAPI), ethidium bromide (EB), or propidium iodide (PI)
      and cleared in xylene (refractive index nu = 1.50), benzyl alcohol/benzyl
      benzoate (BABB; nu = 1.59), xylene-BABB (X-BABB), thiodiglycol (2,2'
      thiodiethanol, nu = 1.52) or anethole (nu = 1.56). Tissue was then paraffin
      embedded for IHC for ER, PR, E-cadherin, CD31 or cytokeratin 7. Haematoxylin and
      alum-carmine are excellent non-fluorescent subgross stains giving strong nuclear
      staining and minimal background. DAPI and EB permeate thick sections poorly but
      PI penetrates well, with a high signal-to-noise ratio after clearing in BABB or X
      BABB. Other clearing agents were less effective, including thiodiglycol.
      Anethole's unpleasant odour precluded further evaluation. All evaluated clearing
      agents preserved comparable immunoreactivity for all markers. PI is a promising
      stain for subgross breast studies, compatible with BABB clearing. The hope that
      the water-miscible thioalcohol, thiodiglycol, might accelerate tissue clearing
      was not realised. There is scope for further streamlining to make subgross
      techniques more acceptable in combined research/diagnostic settings.

PMID- 22460858
TI  - Fibrates and estimated glomerular filtration rate: observations from an
      outpatient clinic setting and clinical implications.
AB  - BACKGROUND: Previous studies have demonstrated that fibrates have an effect on
      creatinine concentrations. The pattern of change with fibrates in estimated
      glomerular filtration rate (eGFR), widely used in clinical practice, has not been
      previously described. METHODS: Data was retrospectively collected from 132
      consecutive case notes of patients started on fibrates in a lipid clinic between
      2002 and 2008. Pre- and post-fibrate creatinine concentrations were measured and
      eGFR measurements were obtained. RESULTS: Of the 79 patients with both pre and
      post-treatment eGFR values <90 ml/min/1.73 m(2), a significant mean eGFR
      reduction of 8.2 ml/min/1.73 m(2) was noted. Of these patients, 50% demonstrated
      a reduction in eGFR >8 ml/min/1.73 m(2), 25% demonstrated a reduction >16
      ml/min/1.73 m(2), and 10% demonstrated a reduction >21 ml/min/1.73 m(2).
      CONCLUSIONS: The authors demonstrate a significant effect of fibrates on eGFR in
      clinical practice. Awareness of the pattern of eGFR change is important for
      decisions regarding the continued use of fibrate therapy and/or commonly co
      prescribed diabetic drugs and renal specialist referrals.

PMID- 22460859
TI  - Must try harder.

PMID- 22460857
TI  - Epithelial to mesenchymal transition in cutaneous squamous cell carcinoma is
      correlated with COX-2 expression but not with the presence of stromal macrophages
      or CD10-expressing cells.
AB  - Epithelial to mesenchymal transition (EMT) is an intricate process by which
      epithelial cells loose epithelial characteristics and acquire a mesenchymal-like
      phenotype. EMT and cyclooxygenase 2 (COX-2) expression are related to tumor
      invasion and metastasis. The tumor microenvironment plays a major role in tumor
      progression and the induction of EMT. Here, we investigated the relationship
      between EMT and COX-2 expression as well as tumor-associated macrophages (TAM)
      and CD10-positive stromal cells during the development of cutaneous squamous
      neoplastic lesion. We performed immunohistochemical staining for vimentin, E
      cadherin, beta-catenin, COX-2, CD68, and CD10 in 41 cases of squamous cell
      cancers (SCC), 20 of Bowen's disease, 30 of actinic keratosis, and 30 samples of
      normal skin. SCC cells showed significantly increased vimentin expression and
      reduced expression of membranous E-cadherin and beta-catenin compared with cells
      in precursor lesions and in normal skin. COX-2 expression was also markedly
      increased in SCC cells. E-cadherin expression was positively correlated with beta
      catenin expression and inversely correlated with COX-2 expression in SCC cells.
      The number of TAM and CD10-positive stromal cells increased from the normal skin
      to precursor lesions and SCC cells. The number of TAM and of CD10-positive
      stromal cells did not correlate with the expression of E-cadherin, beta-catenin,
      COX-2, and vimentin in SCC cells. We suggest that cutaneous SCC cells show EMT,
      which appears to be correlated with COX-2 expression but not with stromal CD10
      expression and TAM.

PMID- 22460860
TI  - Under surveillance.

PMID- 22460861
TI  - Food for thought.

PMID- 22460862
TI  - Scientists must be taught to manage.

PMID- 22460873
TI  - Farm focus for saving trees.

PMID- 22460874
TI  - Drug candidates derailed in case of mistaken identity.

PMID- 22460876
TI  - North set for mass analysis of planets.

PMID- 22460875
TI  - Flu surveillance lacking.

PMID- 22460877
TI  - Chemistry's web of data expands.

PMID- 22460878
TI  - African agriculture: Dirt poor.

PMID- 22460879
TI  - Life-changing experiments: The biological Higgs.

PMID- 22460880
TI  - Drug development: Raise standards for preclinical cancer research.

PMID- 22460881
TI  - H5N1 surveillance: Shift expertise to where it matters.

PMID- 22460882
TI  - H5N1: How to track a flu virus.

PMID- 22460887
TI  - Fossil fuels: Peak oil is affecting the economy already.

PMID- 22460888
TI  - Turing: A formal clash of codes.

PMID- 22460889
TI  - Sustainable development: True value of climate fund's contribution.

PMID- 22460890
TI  - Neuroscience: The case for brain imaging technology.

PMID- 22460891
TI  - Turing: Keep his work in perspective.

PMID- 22460892
TI  - Wylie Walker Vale Jr (1941-2012).

PMID- 22460893
TI  - Drug discovery: Cell lines battle cancer.

PMID- 22460894
TI  - Photonics: Terahertz collisions.

PMID- 22460895
TI  - Cancer: Clinical trials unite mice and humans.

PMID- 22460897
TI  - Palaeoclimate: Tahitian record suggests Antarctic collapse.

PMID- 22460898
TI  - Human evolution: Those feet in ancient times.

PMID- 22460899
TI  - Evidence against a chondritic Earth.
AB  - The (142)Nd/(144)Nd ratio of the Earth is greater than the solar ratio as
      inferred from chondritic meteorites, which challenges a fundamental assumption of
      modern geochemistry--that the composition of the silicate Earth is 'chondritic',
      meaning that it has refractory element ratios identical to those found in
      chondrites. The popular explanation for this and other paradoxes of mantle
      geochemistry, a hidden layer deep in the mantle enriched in incompatible
      elements, is inconsistent with the heat flux carried by mantle plumes. Either the
      matter from which the Earth formed was not chondritic, or the Earth has lost
      matter by collisional erosion in the later stages of planet formation.

PMID- 22460900
TI  - Ice-sheet collapse and sea-level rise at the Bolling warming 14,600 years ago.
AB  - Past sea-level records provide invaluable information about the response of ice
      sheets to climate forcing. Some such records suggest that the last deglaciation
      was punctuated by a dramatic period of sea-level rise, of about 20 metres, in
      less than 500 years. Controversy about the amplitude and timing of this meltwater
      pulse (MWP-1A) has, however, led to uncertainty about the source of the melt
      water and its temporal and causal relationships with the abrupt climate changes
      of the deglaciation. Here we show that MWP-1A started no earlier than 14,650
      years ago and ended before 14,310 years ago, making it coeval with the Bolling
      warming. Our results, based on corals drilled offshore from Tahiti during
      Integrated Ocean Drilling Project Expedition 310, reveal that the increase in sea
      level at Tahiti was between 12 and 22 metres, with a most probable value between
      14 and 18 metres, establishing a significant meltwater contribution from the
      Southern Hemisphere. This implies that the rate of eustatic sea-level rise
      exceeded 40 millimetres per year during MWP-1A.

PMID- 22460901
TI  - A new hominin foot from Ethiopia shows multiple Pliocene bipedal adaptations.
AB  - A newly discovered partial hominin foot skeleton from eastern Africa indicates
      the presence of more than one hominin locomotor adaptation at the beginning of
      the Late Pliocene epoch. Here we show that new pedal elements, dated to about 3.4
      million years ago, belong to a species that does not match the contemporaneous
      Australopithecus afarensis in its morphology and inferred locomotor adaptations,
      but instead are more similar to the earlier Ardipithecus ramidus in possessing an
      opposable great toe. This not only indicates the presence of more than one
      hominin species at the beginning of the Late Pliocene of eastern Africa, but also
      indicates the persistence of a species with Ar. ramidus-like locomotor adaptation
      into the Late Pliocene.

PMID- 22460903
TI  - Observation of a roton collective mode in a two-dimensional Fermi liquid.
AB  - Understanding the dynamics of correlated many-body quantum systems is a challenge
      for modern physics. Owing to the simplicity of their Hamiltonians, (4)He (bosons)
      and (3)He (fermions) have served as model systems for strongly interacting
      quantum fluids, with substantial efforts devoted to their understanding. An
      important milestone was the direct observation of the collective phonon-roton
      mode in liquid (4)He by neutron scattering, verifying Landau's prediction and his
      fruitful concept of elementary excitations. In a Fermi system, collective density
      fluctuations (known as 'zero-sound' in (3)He, and 'plasmons' in charged systems)
      and incoherent particle-hole excitations are observed. At small wavevectors and
      energies, both types of excitation are described by Landau's theory of Fermi
      liquids. At higher wavevectors, the collective mode enters the particle-hole
      band, where it is strongly damped. The dynamics of Fermi liquids at high
      wavevectors was thus believed to be essentially incoherent. Here we report
      inelastic neutron scattering measurements of a monolayer of liquid (3)He,
      observing a roton-like excitation. We find that the collective density mode
      reappears as a well defined excitation at momentum transfers larger than twice
      the Fermi momentum. We thus observe unexpected collective behaviour of a Fermi
      many-body system in the regime beyond the scope of Landau's theory. A
      satisfactory interpretation of the measured spectra is obtained using a dynamic
      many-body theory.

PMID- 22460902
TI  - Systematic identification of genomic markers of drug sensitivity in cancer cells.
AB  - Clinical responses to anticancer therapies are often restricted to a subset of
      patients. In some cases, mutated cancer genes are potent biomarkers for responses
      to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance
      to cancer therapeutics, we screened a panel of several hundred cancer cell lines-
      which represent much of the tissue-type and genetic diversity of human cancers-
      with 130 drugs under clinical and preclinical investigation. In aggregate, we
      found that mutated cancer genes were associated with cellular response to most
      currently available cancer drugs. Classic oncogene addiction paradigms were
      modified by additional tissue-specific or expression biomarkers, and some
      frequently mutated genes were associated with sensitivity to a broad range of
      therapeutic agents. Unexpected relationships were revealed, including the marked
      sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)
      FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By
      linking drug activity to the functional complexity of cancer genomes, systematic
      pharmacogenomic profiling in cancer cell lines provides a powerful biomarker
      discovery platform to guide rational cancer therapeutic strategies.

PMID- 22460904
TI  - Experimental observation of electron-hole recollisions.
AB  - An intense laser field can remove an electron from an atom or molecule and pull
      the electron into a large-amplitude oscillation in which it repeatedly collides
      with the charged core it left behind. Such recollisions result in the emission of
      very energetic photons by means of high-order-harmonic generation, which has been
      observed in atomic and molecular gases as well as in a bulk crystal. An exciton
      is an atom-like excitation of a solid in which an electron that is excited from
      the valence band is bound by the Coulomb interaction to the hole it left behind.
      It has been predicted that recollisions between electrons and holes in excitons
      will result in a new phenomenon: high-order-sideband generation. In this process,
      excitons are created by a weak near-infrared laser of frequency f(NIR). An
      intense laser field at a much lower frequency, f(THz), then removes the electron
      from the exciton and causes it to recollide with the resulting hole. New emission
      is predicted to occur as sidebands of frequency f(NIR) + 2nf(THz), where n is an
      integer that can be much greater than one. Here we report the observation of high
      order-sideband generation in semiconductor quantum wells. Sidebands are observed
      up to eighteenth order (+18f(THz), or n = 9). The intensity of the high-order
      sidebands decays only weakly with increasing sideband order, confirming the non
      perturbative nature of the effect. Sidebands are strongest for linearly polarized
      terahertz radiation and vanish when the terahertz radiation is circularly
      polarized. Beyond their fundamental scientific significance, our results suggest
      a new mechanism for the ultrafast modulation of light, which has potential
      applications in terabit-rate optical communications.

PMID- 22460908
TI  - FEIBA: a prohemostatic agent.
AB  - Factor eight inhibitor bypassing activity (FEIBA), Anti-Inhibitor Coagulation
      Complex has been used for over 30 years in hemophiliac patients with inhibitors.
      The history of its use is reviewed here, including issues related to thrombosis,
      efficacy, and comparison to alternative bypassing agents. The need for surrogate
      assays to monitor effective hemostasis with the use of FEIBA remains.

PMID- 22460906
TI  - Deregulated MYC expression induces dependence upon AMPK-related kinase 5.
AB  - Deregulated expression of the MYC oncoprotein contributes to the genesis of many
      human tumours, yet strategies to exploit this for a rational tumour therapy are
      scarce. MYC promotes cell growth and proliferation, and alters cellular
      metabolism to enhance the provision of precursors for phospholipids and cellular
      macromolecules. Here we show in human and murine cell lines that oncogenic levels
      of MYC establish a dependence on AMPK-related kinase 5 (ARK5; also known as
      NUAK1) for maintaining metabolic homeostasis and for cell survival. ARK5 is an
      upstream regulator of AMPK and limits protein synthesis via inhibition of the
      mammalian target of rapamycin 1 (mTORC1) signalling pathway. ARK5 also maintains
      expression of mitochondrial respiratory chain complexes and respiratory capacity,
      which is required for efficient glutamine metabolism. Inhibition of ARK5 leads to
      a collapse of cellular ATP levels in cells expressing deregulated MYC, inducing
      multiple pro-apoptotic responses as a secondary consequence. Depletion of ARK5
      prolongs survival in MYC-driven mouse models of hepatocellular carcinoma,
      demonstrating that targeting cellular energy homeostasis is a valid therapeutic
      strategy to eliminate tumour cells that express deregulated MYC.

PMID- 22460905
TI  - The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug
      sensitivity.
AB  - The systematic translation of cancer genomic data into knowledge of tumour
      biology and therapeutic possibilities remains challenging. Such efforts should be
      greatly aided by robust preclinical model systems that reflect the genomic
      diversity of human cancers and for which detailed genetic and pharmacological
      annotation is available. Here we describe the Cancer Cell Line Encyclopedia
      (CCLE): a compilation of gene expression, chromosomal copy number and massively
      parallel sequencing data from 947 human cancer cell lines. When coupled with
      pharmacological profiles for 24 anticancer drugs across 479 of the cell lines,
      this collection allowed identification of genetic, lineage, and gene-expression
      based predictors of drug sensitivity. In addition to known predictors, we found
      that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors;
      AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines;
      and SLFN11 expression predicted sensitivity to topoisomerase inhibitors.
      Together, our results indicate that large, annotated cell-line collections may
      help to enable preclinical stratification schemata for anticancer agents. The
      generation of genetic predictions of drug response in the preclinical setting and
      their incorporation into cancer clinical trial design could speed the emergence
      of 'personalized' therapeutic regimens.

PMID- 22460909
TI  - Fibrinogen as a hemostatic agent.
AB  - Coagulation factor I (fibrinogen) plays an essential role in the hemostatic
      system by bridging activated platelets and being the key substrate for thrombin
      in establishing a consolidating fibrin network. Fibrinogen is synthesized in the
      liver and the plasma concentration is 1 to 5-4.0 g/L. During recent 10 years,
      fibrinogen has been recognized to play an important role in controlling
      hemorrhage. Dilutional coagulopathy induced by colloid plasma expanders is
      characterized by fibrinogen deficiency and dysfunctional fibrin polymerization.
      Trauma and use of extracorporeal circulation is also known to reduce levels of
      fibrinogen. A series of laboratory experiments and experimental animal studies
      have suggested fibrinogen as a potent hemostatic agent. These data are supported
      by retrospective surveys as well as a series of prospective proof of principal
      clinical trials. This article provides a description of the biochemistry and
      mechanisms of fibrinogen as well as the etiology for developing fibrinogen
      deficiency. Furthermore, it summarizes laboratory and experimental data on the
      role of fibrinogen in dilutional coagulopathy and addresses laboratory monitoring
      issues. Finally, it lists retrospective and prospective studies, which have been
      designed to assess the clinical efficacy and safety of hemostatic intervention
      with fibrinogen concentrate.

PMID- 22460910
TI  - Early diagnosis and treatment for remission of clinically amyopathic
      dermatomyositis complicated by rapid progress interstitial lung disease: a report
      of two cases.
AB  - We report two cases of clinically amyopathic dermatomyositis (CADM) complicated
      by rapid progress interstitial lung disease (RPILD). The diagnosis of CADM was
      based on Gottron's papule and RPILD, and the absence of muscle weakness. The
      female patients were treated with early immunosuppressive therapies including
      steroid pulse therapy, resulting in significant improvement in respiratory
      symptoms, clinical data, and imaging. Measurement of anti-CADM-140/MDA5 antibody
      was useful for obtaining a definitive diagnosis of CADM in these cases.

PMID- 22460911
TI  - Francis Sibson (1814-1876): the unsung hero of modern surgery and anesthesia.
AB  - Francis Sibson (1814-1876) was a British physician and anatomist widely regarded
      as a true pioneer of the medical profession. He overcame a tragic and difficult
      childhood to become an avid educator at several medical schools and dedicated his
      life to research. For modern scientists, he is most remembered for describing
      Sibson's fascia, his experimental use of curare in the treatment of hydrophobia
      and tetanus, and his detailed description of the positions and movements of
      internal organs. He died on September 7, 1876 at the age of 62 from complications
      of an aortic aneurysm.

PMID- 22460913
TI  - Identification and biocontrol efficacy of Streptomyces miharaensis producing
      filipin III against Fusarium wilt.
AB  - A number of bacterial strains were isolated from the internal tissue of Trapa
      japonica. Of these, strain KPE62302H, which had a 16S rDNA sequence identical to
      that of Streptomyces miharaensis showed antifungal activity against several plant
      pathogens. Treatment of seeds with strain KPE62302H induced a significant
      reduction in the incidence of Fusarium wilt in tomato plants compared with
      untreated controls. An antifungal substance (FP-1) was purified from the culture
      extract of strain KPE62302H using C18 flash and Sephadex LH-20 column
      chromatography and reverse phase HPLC. Extensive spectrometric analysis using MS
      and NMR identified this as filipin III. FP-1 inhibited the mycelial growth of
      plant pathogenic fungi such as Alternaria mali, Aspergillus niger, Colletotrichum
      gloeosporioides, C. orbiculare, Cylindrocarpon destructans, Diaporthe citiri,
      Fusarium oxysporum at 1-10 MUg ml(-1) and also markedly inhibited the development
      of Fusarium wilt caused by F. oxysporum f.sp. lycopersici in tomato plants by
      treatment with 10 MUg ml(-1) under greenhouse conditions. The efficacy of FP-1
      against Fusarium wilt was comparable to that of the synthetic fungicide benomyl.
      An egfp -tagged strain of KPE62302H confirmed its ability to colonize tomato
      plants.

PMID- 22460914
TI  - Characterization of a versatile rhizospheric organism from cucumber identified as
      Ochrobactrum haematophilum.
AB  - Several rhizobacteria play a vital role in promoting plant growth and protecting
      plants against fungal diseases and degrading pesticides in the environment. In
      this study, a bacterial strain, designated H10, was isolated from the rhizosphere
      at Laixi in Shandong Province, China, and was identified as Ochrobactrum
      haematophilum based on API 20 NE tests and 16S rRNA gene sequence analysis. The
      plant growth-promoting characteristics of the strain were further characterized,
      and the results showed that strain H10 produces siderophore, indol-3-acetic (IAA)
      and solubilized phosphate but lacks 1-aminocyclopropane-1-carboxylate (ACC)
      deaminase activity. Inoculation with the strain was found to significantly
      increase (p < 0.05) the growth of cucumber in pot experiments. Strain H10 was
      assessed in vitro for antagonism against several pathogenic fungi and showed high
      antifungal activity. The cell-free culture filtrates, which had high
      extracellular chitinase, beta-1,3-glucanase and protease activities, could
      inhibit the growth of all pathogenic fungi tested, indicating that growth
      suppression was partly due to extracellular antifungal metabolites present in the
      culture filtrates. Changes in hyphal morphology were observed in phytopathogenic
      fungi after treatment with the culture filtrates. Additionally, strain H10 was
      able to degrade 80%, 85% and 58% of the pesticides chlorpyrifos, beta
      cypermethrin and imidacloprid, respectively, within 60 h in liquid culture. The
      inoculation of strain H10 into soil treated with 100 mg kg(-1) of the three
      pesticides accordingly resulted in a higher degradation rate than in
      noninoculated soils. These results highlight the potential of this bacterium for
      use as a biofertilizer and biopesticide and suggest that it may provide an
      alternative to the use of chemical fertilizers and pesticides in agriculture.
      Additionally, it may represent a bioremediation agent that can remove
      contaminating chemical pesticide residues from the environment.

PMID- 22460916
TI  - On modeling biomolecular-surface nonbonded interactions: application to
      nucleobase adsorption on single-wall carbon nanotube surfaces.
AB  - In this work we explored the selectivity of single nucleobases towards adsorption
      on chiral single-wall carbon nanotubes (SWCNTs) by density functional theory
      calculations. Specifically, the adsorption of molecular models of guanine (G),
      adenine (A), thymine (T), and cytosine (C), as well as of AT and GC Watson-Crick
      (WC) base pairs on chiral SWCNT C(6, 5), C(9, 1) and C(8, 3) model structures,
      was analyzed in detail. The importance of correcting the exchange-correlation
      functional for London dispersion was clearly demonstrated, yet limitations in
      modeling such interactions by considering the SWCNT as a molecular model may mask
      subtle effects in a molecular-macroscopic material system. The trend in the
      calculated adsorption energies of the nucleobases on same diameter C(6, 5) and
      C(9, 1) SWCNT surfaces, i.e., G > A > T > C, was consistent with related
      computations and experimental work on graphitic surfaces, however contradicting
      experimental data on the adsorption of single-strand short homo-oligonucleotides
      on SWCNTs that demonstrated a trend of G > C > A > T (Albertorio et al 2009
      Nanotechnology 20 395101). A possible role of electrostatic interactions in this
      case was partially captured by applying the effective fragment potential method,
      emphasizing that the interplay of the various contributions in modeling nonbonded
      interactions is complicated by theoretical limitations. Finally, because the
      calculated adsorption energies for Watson-Crick base pairs have shown little
      effect upon adsorption of the base pair farther from the surface, the results on
      SWCNT sorting by salmon genomic DNA could be indicative of partial unfolding of
      the double helix upon adsorption on the SWCNT surface.

PMID- 22460917
TI  - Organization of the sensory system of the earthworm Lumbricus terrestris
      (Annelida, Clitellata) visualized by DiI.
AB  - The anatomical organization of the peripheral and central sensory structures of
      the earthworm Lumbricus terrestris was investigated applying a fluorescent
      carbocyanine dye (DiI) as a neuronal tracer. Using whole-mount preparations and
      confocal laser scanning microscopy, the pattern of primary sensory cells and
      pathways of their processes were traced and reconstructed in three-dimensions.
      Our study shows that a ventral nerve cord ganglion receives sensory fibers from
      at least two adjacent segments suggesting that the peripheral nervous system is
      not segmental in its arrangement and the receptive-fields of the body wall
      overlap in earthworms. Furthermore, our result suggests an integrative function
      of the basiepidermal plexus consists of sensory and motor fibers.

PMID- 22460919
TI  - Characterisation of the paramagnetic [2Fe-2S]+ centre in palustrisredoxin-B
      (PuxB) from Rhodopseudomonas palustris CGA009: g-matrix determination and spin
      coupling analysis.
AB  - Palustrisredoxin-B (PuxB) from Rhodopseudomonas palustris (CGA009) is a [2Fe-2S]
      ferredoxin which is able to accept electrons from NADH via the flavin-dependent
      palustrisredoxin reductase (PuR); these electrons can then be transferred to the
      P450 enzyme (CYP199A2). This work reports on the paramagnetic state of the [2Fe
      2S](+) cluster in PuxB, both alone and in the PuR-PuxB complex. Aided by the X
      ray crystal structure of PuxB, the protons nearest to the reduced [2Fe-2S](+)
      cluster were used as magnetic probes to quantify the g-matrix orientation and
      anisotropic magnetic moment of the paramagnetic centre. (1)H hyperfine couplings
      were measured with W-band Davies ENDOR and X-band HYSCORE spectroscopy and fitted
      to a model in which (1)H dipolar couplings were calculated assuming point
      magnetic moments located at the Fe ions, and bridging and coordinating cysteine
      sulfur atoms. The absolute sign of a (1)H hyperfine coupling was measured using a
      variable mixing time ENDOR experiment to confirm the assignment of the Fe(3+) and
      Fe(2+) ions. For the anti-ferromagnetically coupled cluster the magnetic moment
      is described in terms of spin projection factors, and our analysis yields values
      of K(exp)(A) = +2.33 to +1.85 (ferric site), and K(exp)(B) = -1.33 to -0.85
      (ferrous site). These values are discussed in terms of the delocalisation of the
      spin density and hence the limitations of applying a local site spin coupling
      model to calculate the spin projection factors in a complex with considerable
      overlap of the alpha- and beta-spin magnetic oribitals. The accurate description
      of the g-matrix orientation and magnetic moment of this [2Fe-2S](+) cluster
      enable it to be utilised as a paramagnetic spin probe, for example, to measure
      electron-electron distances. In the pdb reference frame of PuxB (code ) the g(?)
      axis vector is g(?) = [-0.6524 +/- 0.0248, -0.6269 +/- 0.0115, 0.4259 +/-
      0.0405], with the principal g-values of g(?) = 1.9328 +/- 0.0003, g(?) = 2.0233
      +/- 0.0003.

PMID- 22460918
TI  - Extensive cell migration, axon regeneration, and improved function with
      polysialic acid-modified Schwann cells after spinal cord injury.
AB  - Schwann cell (SC) implantation after spinal cord injury (SCI) promotes axonal
      regeneration, remyelination repair, and functional recovery. Reparative efficacy,
      however, may be limited because of the inability of SCs to migrate outward from
      the lesion-implant site. Altering SC cell surface properties by overexpressing
      polysialic acid (PSA) has been shown to promote SC migration. In this study, a
      SCI contusion model was used to evaluate the migration, supraspinal axon growth
      support, and functional recovery associated with polysialyltransferase (PST)
      overexpressing SCs [PST-green fluorescent protein (GFP) SCs] or controls (GFP
      SCs). Compared with GFP SCs, which remained confined to the injection site at the
      injury center, PST-GFP SCs migrated across the lesion:host cord interface for
      distances of up to 4.4 mm within adjacent host tissue. In addition, with PST-GFP
      SCs, there was extensive serotonergic and corticospinal axon in-growth within the
      implants that was limited in the GFP SC controls. The enhanced migration of PST
      GFP SCs was accompanied by significant growth of these axons caudal to lesion.
      Animals receiving PST-GFP SCs exhibited improved functional outcome, both in the
      open-field and on the gridwalk test, beyond the modest improvements provided by
      GFP SC controls. This study for the first time demonstrates that a lack of
      migration by SCs may hinder their reparative benefits and that cell surface
      overexpression of PSA enhances the ability of implanted SCs to associate with and
      support the growth of corticospinal axons. These results provide further promise
      that PSA-modified SCs will be a potent reparative approach for SCI. (c) 2012
      Wiley Periodicals, Inc.

PMID- 22460920
TI  - Electrical sorting of Caenorhabditis elegans.
AB  - The nematode (worm) C. elegans is one of the widely studied animal model
      organisms in biology. It develops through 4 larval stages (L1-L4) in 2 to 3 days
      before becoming a young adult. Biological assays involving C. elegans frequently
      require a large number of animals that are appropriately staged and exhibit a
      similar behaviour. We have developed a new method to synchronize animals that
      relies on the electrotactic response (electric field-induced motion) of C.
      elegans to sort them in parallel based on their age, size and phenotype. By using
      local electric field traps in a microfluidic device, we can efficiently sort
      worms from a mixed culture in a semi-continuous flow manner (with a minimum
      throughput of 78 worms per minute per load-run) and obtain synchronized
      populations of animals. In addition to sorting larvae, our device can also
      distinguish between young and old adults efficiently. Unlike fluorescent based
      sorting systems that use active imaging based feedback, this method is passive
      and automatic and uses the innate behaviour of the worm. Considering that the
      entire procedure takes only a few minutes to run and is cost-effective, it
      promises to simplify and accelerate experiments requiring homogeneous cultures of
      worms as well as to facilitate isolation of mutants that have abnormal
      electrotaxis. More importantly, our method of isolating and separating worms
      using locomotion as a defining characteristic promises development of advanced
      microfluidics-based systems to study the neuronal basis of movement-related
      defects in worms and facilitate high-throughput chemical screening and drug
      discovery.

PMID- 22460921
TI  - Postoperative trunk shift in Lenke 1C scoliosis: what causes it? How can it be
      prevented?
AB  - STUDY DESIGN: A risk factor analysis study. OBJECTIVE: To identify the causative
      factors for postoperative trunk shift in Lenke 1C scoliosis and investigate how
      to prevent it. SUMMARY OF BACKGROUND DATA: When selective thoracic fusion is
      performed, postoperative trunk shift is a significant problem in the management
      of Lenke 1C scoliosis. It is often accompanied by unsatisfactory clinical
      outcomes and a risk of reoperation. METHODS: We reviewed all the patients with
      adolescent idiopathic scoliosis (AIS) surgically treated in our institution from
      2002 through 2008. Inclusion criteria were as follows: (1) patients with Lenke 1C
      curves who were treated with selective thoracic fusion using posterior pedicle
      screw-only constructs; (2) the lowest instrumented vertebra (LIV) ending at L1
      level or above; and (3) 2-year radiographical follow-up. Eighteen radiographical
      parameters were chosen as potential risk factors. The 18 parameters measured (1)
      amount of correction obtained by surgery; (2) preoperative position of LIV; (3)
      magnitude of major thoracic and thoracolumbar/lumbar (MT and TL/L) curves and
      ratio of MT: TL/L curve; and (4) curve flexibility. Both comparative and
      correlation analyses were performed. Those parameters that had shown highest
      correlation with the 2-year thoracic apical vertebra-center sacral vertical line
      (AV-CSVL) distance were selected to form a linear regression model, by which the
      correlations were quantified. RESULTS: Of the 278 patients reviewed, 44 met the
      inclusion criteria. The parameters that measured the preoperative position of LIV
      and ratio of MT: TL/L curve showed high correlation with the 2-year thoracic AV
      CSVL distance. With regard to the parameters that measured the amount of
      correction obtained by surgery, only the correction of the thoracic AV-T1
      distance showed low correlation. Among the 18 parameters, preoperative lowest
      instrumented vertebra-lower end vertebra (LIV-LEV) difference and ratio of MT:
      TL/L Cobb angle were selected to form a formula to help predict postoperative
      trunk shift. The formula was as follows: 2-year thoracic AV-CSVL distance = -26.6
      + 22.7 (ratio of MT: TL/L Cobb angle) - 3.9 (preoperative LIV-LEV difference).
      The model R2 = 0.55. CONCLUSION: Both LIV selection and ratio of MT: TL/L curve
      were found to be highly correlated with the onset of postoperative trunk shift in
      Lenke 1C scoliosis. Amount of correction obtained by surgery, however, did not
      seem to be an independent causative factor. Postoperative trunk shift is less
      likely to occur when selecting LEV as LIV and the ratio of MT: TL/L Cobb angle of
      1.2 degrees  or more.

PMID- 22460922
TI  - Racial differences in the incidence of acute low back pain in United States
      military service members.
AB  - STUDY DESIGN: An epidemiological study. OBJECTIVE: To determine the effect of
      race on the incidence of acute low back pain, resulting in a health care
      encounter in active duty military service members. SUMMARY OF BACKGROUND DATA:
      Although racial differences in the incidence of low back pain have been
      documented in previous studies, currently no consensus exists on the relative
      risk between these groups. METHODS: A query was performed using the Armed Forces
      Health Surveillance Center database for the International Classification of
      Diseases, Ninth Revision code for low back pain (724.20). A total of 12,399,276
      person-years of data were analyzed and stratified by age, race, and sex.
      Incidence rates were calculated and compared using the multivariate Poisson
      regression analysis. RESULTS: A total of 467,950 cases of low back pain resulted
      in a visit to a health care provider in our population, with an overall incidence
      rate of 37.74 per 1000 person-years. Asians/Pacific Islanders had the lowest
      incidence rate of 30.7 and blacks had the highest with 43.7. Female sex and older
      age were also significant risk factors but with significantly different effect
      sizes between racial groups. Native Americans/Alaskan Natives demonstrated the
      greatest effect of age on low back pain incidence rates, with a 126% increase
      between the youngest and oldest age groups compared with a 36% difference in
      whites. CONCLUSION: Race, sex, and age were all found to be significant risk
      factors for acute low back pain. The highest rates were identified in blacks
      followed by whites, Hispanics, and American Indian/Alaskan Native, and the lowest
      rates were identified in Asians/Pacific Islanders. Significant differences in the
      effect of sex and age were identified between the different racial groups.

PMID- 22460923
TI  - Symptoms of post-traumatic stress following elective lumbar spinal arthrodesis.
AB  - STUDY DESIGN: A prospective cohort study with 100% follow-up. OBJECTIVE: To
      assess incidence and risk factors for development of post-traumatic stress
      disorder (PTSD) symptoms after elective lumbar arthrodesis. SUMMARY OF BACKGROUND
      DATA: Invasive medical care results in substantial physical and psychological
      stress to patients. The reported incidence of PTSD after medical care delivery in
      patients treated for trauma, cancer, and organ transplantation ranges from 5% to
      51%. Similar data after elective lumbar spinal arthrodesis have not been
      reported. METHODS: A consecutive series of 73 elective lumbar spine arthrodesis
      patients were evaluated prospectively, using the PTSD checklist-civilian version
      at 6 weeks, 3 months, 6 months, 9 months, and 12 months after surgery. Patient's
      sex, age, education level, job status, marital status, psychiatric history, prior
      surgery with general anesthetic, surgical approach, blood loss, postoperative
      intubation, length of intensive care unit and hospital stay, and occurrence of
      perioperative complications were analyzed as predictors of PTSD symptoms, using
      chi analyses. RESULTS: The overall incidence of symptoms of PTSD identified at at
      least 1 time point was 19.2% (14 of 73). At each time point, the percentage of
      the population that was positive was 7.5% (6 wk), 11.6% (3 mo), 7.8%, (6 mo),
      13.6% (9 mo), and 11.0% (12 mo). The presence of a prior psychiatric diagnosis
      proved to be the strongest predictor of postarthrodesis symptoms of PTSD (odds
      ratio [OR] = 7.05, P = 0.002). Occurrence of a complication also proved to be
      significantly correlated with the development of PTSD symptoms (OR = 4.33, P =
      0.04). Age less than 50 years, blood loss of more than 1 L, hospital stay of more
      than 10 days, and diagnosis trended toward but failed to reach statistical
      significance. None of the remaining variables approached statistical
      significance. CONCLUSION: Positive PTSD symptoms occurred at least once in 19.2%
      of patients after elective lumbar arthrodesis, with 7.5% to 13.6% of patients
      experiencing these symptoms at any 1 time point postoperatively. In this patient
      cohort, preoperative psychiatric diagnosis was the strongest predictor among
      tested variables of occurrence of PTSD symptoms, although occurrence of a
      perioperative complication was also significantly correlated with PTSD symptoms.
      Spine surgeons should be aware of the potential impact of lumbar arthrodesis
      surgery on patients' psychological state. Further investigation focusing on the
      impact of PTSD symptoms on clinical outcomes as well as on potential means of
      reducing the postoperative incidence of this disorder seems warranted.

PMID- 22460924
TI  - Simultaneous posterior and anterior approaches with posterior vertebral wall
      preserved for rigid post-traumatic kyphosis in thoracolumbar spine.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate the radiological and
      clinical results of simultaneous surgery with preservation of the posterior
      vertebral wall for rigid post-traumatic kyphosis in the thoracolumbar spine.
      SUMMARY OF BACKGROUND DATA: Management of rigid post-traumatic kyphosis has been
      a challenge for surgeons. Current widely used posterior osteotomy procedures have
      the disadvantages of significant invasiveness, spinal column shortening, and
      instrumentation-related complications. METHODS: From 2004 to 2009, 21 patients
      with rigid post-traumatic kyphosis in the thoracolumbar spine (T11-L2) were
      managed in our hospital. Average kyphotic angle was 45.2 degrees  +/- 11.2
      degrees  (range, 31 degrees -67 degrees ). The surgical technique used was
      posterior and anterior circumferential release and anterior corpectomy with
      posterior vertebral wall preservation and short segmental instrumentation.
      Preoperative and postoperative kyphotic angle was measured to assess the degree
      of kyphosis correction and maintenance. Changes in low back pain were assessed by
      Japanese Orthopaedic Association scores. RESULTS: All patients were successfully
      managed with this procedure without major complications. Most patients (19 of 21)
      were instrumented with anterior-only fixation, while posterior interspinal wire
      was added in 2 patients with osteoporosis. The mean blood loss was 470 mL (range,
      300-700 mL). Patients were followed for an average of 32 months (range, 6-70 mo)
      postoperatively. Back pain was relieved to some degree in all patients and the
      improvement in Japanese Orthopaedic Association scores was 76.9% +/- 7.9. Average
      kyphotic angle was 6.0 degrees  +/- 5.7 degrees  (range, -2 to 17) immediately
      after surgery and 7.2 degrees  +/- 5.8 degrees  (range, -3 to 17) at final follow
      up. Average of 1 degrees  of correction loss was documented and all patients
      obtained solid fusion uneventfully. CONCLUSION: This technique is indicated for
      most patients with rigid post-traumatic kyphosis in the thoracolumbar spine and
      can yield satisfactory clinical results not only in terms of pain relief,
      kyphosis correction, vertebral height restoration, and spinal canal integrity
      preservation, but also in reducing the risk of excessive bleeding and spinal cord
      injury.

PMID- 22460925
TI  - Clinical evaluation of the Sorin Xtra(R) Autotransfusion System.
AB  - The performance of the Sorin Xtra(r) Autotransfusion System (ATS) was studied in
      62 patients undergoing coronary artery bypass grafting. Blood was collected
      intraoperatively and washed using three different wash sets in 4 groups. Both
      collected and washed blood were analysed for hemoglobin levels and hematocrit,
      concentrations of proteins, albumin, heparin and plasma free hemoglobin (PFH)
      were determined, erythrocytes, platelets and leukocytes were counted. Hematocrit
      measurements of the Xtra(r) were compared with laboratory measurements to study
      the accuracy of the Xtra(r) hematocrit sensor. In addition, the red blood cell
      recovery rate and elimination rates were calculated to evaluate the clinical
      performance of the Xtra(r). The Xtra(r) ATS produced a volume of concentrated red
      blood cells with an average hematocrit from 58% to 63%, depending on the size of
      the bowl and the chosen default program. In all bowl sizes and programs, the
      Xtra(r) Hct-out measurement underestimated the CELL-DYN measurement by
      approximately 15%. The calculated recovery rates for red blood cells (RBC) in the
      4 groups ranged from 86.7% to 91.6%. Elimination rates were calculated in each
      group for proteins (96.8-99.2%), albumin (96.4-98.7%), plasma free hemoglobin
      (83.6-91.2%), heparin (98.8-99.9%), platelets (82.4-94.3%) and white blood cells
      (28.6-42.3%). The Xtra(r) ATS can be appealing for its performance by producing
      high hematocrit levels in the washed RBC volume, while keeping RBC recovery rate
      at the same high level (~ 90%) as in its predecessor, the Electa(r)
      Autotransfusion System.

PMID- 22460926
TI  - THE PAPWORTH PLUG - successful use of high dose fibrinogen concentrate and
      platelet concentrate in potential life-threatening complication after
      cardiopulmonary bypass surgery in a patient with Type 2M Vicenza von Willebrand
      Disease.
AB  - Anecdotally, fibrinogen concentrate (FC) has been used as a "universal"
      haemostatic agent in complex post-cardiopulmonary bypass (CPB) coagulopathy. We
      present a case where FC and two pools of platelets prevented life-threatening
      bleeding in a patient with moderate von Willebrand Disease (vWD) immediately post
      CPB.

PMID- 22460927
TI  - Consumer empowerment and self-advocacy outcomes in a randomized study of peer-led
      education.
AB  - This study examined the effectiveness of the Building Recovery of Individual
      Dreams and Goals (BRIDGES) peer-led education intervention in empowering mental
      health consumers to become better advocates for their own care. A total of 428
      adults with mental illness were randomly assigned to BRIDGES (intervention
      condition) or a services as usual wait list (control condition). Interviews were
      conducted at enrollment, at the end of the intervention, and 6-months post
      intervention. Random regression results indicate that, compared to controls,
      BRIDGES participants experienced significant increases in overall empowerment,
      empowerment-self-esteem, and self-advocacy-assertiveness, and maintained these
      improved outcomes over time. Peer-led education interventions may provide
      participants with the information, skills and support they need to become more
      actively involved in the treatment decision-making process.

PMID- 22460928
TI  - Negative affect predicts adults' ratings of the current, but not childhood,
      impact of adverse childhood events.
AB  - Adverse childhood events (ACE's) have been empirically related to a wide range of
      negative health and mental health outcomes. However, not all individuals who
      experience ACE's follow a trajectory of poor outcomes, and not all individuals
      perceive the impact of ACE's as necessarily negative. The purpose of this study
      was to investigate positive and negative affect as predictors of adults' ratings
      of both the childhood and adult impact of their childhood adversity. Self-report
      data on ACE experiences, including number, severity, and 'impact' were collected
      from 158 community members recruited on the basis of having adverse childhood
      experiences. Results indicated that, regardless of event severity and number of
      different types of adverse events experienced, high levels of negative affect
      were the strongest predictor of whether the adult impact of the adverse childhood
      events was rated as negative. All individuals rated the childhood impact of
      events the same. Implications are discussed.

PMID- 22460929
TI  - Genetics and psychiatry: a proposal for the application of the precautionary
      principle.
AB  - The paper suggests an application of the precautionary principle to the use of
      genetics in psychiatry focusing on scientific uncertainty. Different levels of
      uncertainty are taken into consideration--from the acknowledgement that the
      genetic paradigm is only one of the possible ways to explain psychiatric
      disorders, via the difficulties related to the diagnostic path and genetic
      methods, to the value of the results of studies carried out in this field.
      Considering those uncertainties, some measures for the use of genetics in
      psychiatry are suggested. Some of those measures are related to the conceptual
      limits of the genetic paradigm; others are related to present knowledge and
      should be re-evaluated.

PMID- 22460931
TI  - CCN3: the-pain-killer inside me.
AB  - There is increasing evidence that metalloproteinases are involved in neuropathic
      pain [Dev et al., Expert Opin Investig Drugs 19:455-468 2010] Hence, the
      identification of molecules that can regulate MMP9 and MMP2 is warranted. In a
      recent publication, Kular et al. (2012) claim that CCN3 functions to decrease
      inflammatory pain via the regulation of two metalloproteinases, MMP2 and MMP9, in
      response to experimentally-induced inflammation. Their conclusion is based on the
      following observations : i) the expression of CCN3 was reduced following
      induction of pain by subcutaneous injection of complete Freund's adjuvent in
      rat's paw, ii) an inhibition of MMP9 decreased CFA-associated mechanical
      allodynia, iii) inhibition of CCN3 expression by siRNA led to an upregulation of
      MMP2 in the dorsal horn of the spinal cord (DHSC) and MMP9 in the dorsal root
      ganglia (DRG), iv) a partial effect of CCN3 on CFA-induced expression of MMP9 and
      MMP2 in DRG and DHSC following intrathecal injection of CCN3. Unfortunately, the
      conclusion of this study is weakened by the lack of experimental evidence showing
      a direct relationship between the expression of CCN3 and MMPs. Furthermore,
      several results contained in this manuscript only confirm data that were
      previously established by others. Owing to the wide range of activities which
      have been attributed to CCN3 (Perbal, Mol Pathol 54:57-79 2001, Brigstock, J
      Endocrinol 178:169-175 2003, Perbal, Lancet 363(9402):62-64 2004, Perbal, Cell
      Commun Signal 4:6 2006, Holbourn et al. Trends Biochem Sci. 33:461-473 2008,
      Leask and Abraham, J Cell Sci 119:4803-4810 2006, Jun and Lau, Nat Rev Drug
      Discov 10:945-963 2011, Rachfal and Brigstock, Vitam Horm 70:69-103 2005), the
      mechanisms underlying the potential role of CCN3 in the expression of these MMPs
      in the context of inflammatory pain must be thoroughly studied before a
      meaningful conclusion can be reached. Indeed, Kular et al. description of
      variations in CCN3, MMP9 and MMP2 levels occurring simultaneously is not
      sufficient to draw a functional relationship between these three proteins. It
      should be noted that the expression of CCN3 was already reported to repress MMP9
      (Benini et al., Oncogene 24:4349-4361 2005, Fukunaga-Kalabis et al., Oncogene
      27:2552-2560 2008) and the roles of CCN3 in inflammatory processes has been
      extensively documented in the past few years (Bleau et al., Front Biosci 10:998
      1009 2005, Lin et al., J Biol Chem 280:8229-8237 2005, Perbal, Cell Commun Signal
      4:6 2006, Hughes et al., Diabetologia 50:1089-1098 2007, Lin et al., J Cell
      Commun Signal 4:141-153 2010, Pasmant et al., J Neuropathol Exp Neurol 69:60-69
      2010, Shimoyama et al., Thromb Vasc Biol 30:675-682 2010, Lemaire et al., J
      Invest Dermatol 130:2517 2010, Chen and Lau, J Cell Commun Signal 4:63-69 2010,
      Le Dreau et al., Glia 58:1510-1521 2010, Rittie et al. J Cell Commun Signal 5:69
      80 2011, Janune et al., J Cell Commun Signal 5:167-171 2011). In addition, the
      expression of CCN3 in the neurons of dorsal root ganglia and dorsal horn of the
      spinal horn in rat and human has also been documented (Su et al., C R Acad Sci
      III 321:883-892 1998, Mol Pathol 54:184-191 2001, Kocialkowski et al., Anat
      Embryol (Berl) 203:417-427 2001). Implication of CCN3 in cognitive functions (Su
      et al., Sheng Li Xue Bao 52:290-294 2000) and the possible involvement of CCN3 in
      the regulation of pain was already suggested almost a decade ago (Perbal, Expert
      Rev Mol Diagn 3:597-604 2003, Perbal et al., Mol Pathol 56:80-85 2003) with the
      demonstration of cell-specific effects of CCN3 on intracellular calcium stores
      and inhibition of anionic channels by CCN3 (Li et al., Mol Pathol 55:250-261
      2002, Lombet et al., Cell Commun Signal 1:1 2003, Perbal, Expert Rev Mol Diagn
      3:597-604 2003, Perbal et al., Mol Pathol 56:80-85 2003). Aside from these
      general aspects, and in the light of the potential participation of CCN3 in the
      whole process of pain sensing, the reader would have appreciated the discussion
      in this manuscript not being essentially a flat summary of the data presented,
      but a more thorough discussion of the possible role for CCN3 in the regulation of
      MMPs and its significance in the context of the wide biological functions of
      CCN3.

PMID- 22460930
TI  - TRIP-1: a regulator of osteoblast function.
AB  - Transforming growth factor beta (TGFbeta) receptor interacting protein-1 (TRIP-1)
      is an intracellular protein expressed in osteoblasts with high affinity for type
      5b tartrate resistant acid phosphatase (TRAP). It is suggested that through this
      interaction, TRIP-1 serves as a positive regulator of TGFbeta signaling and
      osteoblast differentiation during bone remodeling. We show here that TRIP-1 is
      abundant in osteoblasts in vivo and in vitro. TRIP-1 mRNA and protein expression
      were increased at early stages and decreased at later stages during osteoblast
      differentiation, suggesting a predominant role during early maturation. To
      investigate a role during bone remodeling, primary osteoblasts were treated with
      different hormones and factors that are known to affect remodeling. TRIP-1 levels
      were decreased with dexamethasone and increased with vitamin D(3) ,
      dihydrotestosterone (DHT), TGFbeta1, and bone morphogenic protein 2 (BMP-2).
      Treatment with parathyroid hormone (PTH) and beta-estradiol did not affect TRIP-1
      levels. Transfected small interfering RNA (siRNA) against TRIP-1 inhibited
      osteoblast differentiation as characterized by a decrease in alkaline phosphatase
      staining and enzyme activity, and decrease in the expression of collagen I,
      alkaline phosphatase, Runx2, osteopontin, and osteocalcin. The proliferation of
      osteoblasts was also affected by TRIP-1 siRNA. This particular effect was defined
      by decreased cell number, marked reduction of cyclin D1, a 38% decrease of cells
      in S phase (p < 0.001) and a 97% increase of cells in the G2/M phase (p < 0.01)
      of the cell cycle. However, TRIP-1 siRNA did not induce an effect in apoptosis.
      Using a TGFbeta luciferase reporter we found that knocking down TRIP-1 decreased
      the activation of TGFbeta signaling by 40% percent (p < 0.001). In conclusion,
      our characterization of TRIP-1 in osteoblasts provides the first evidence of its
      key role as a positive regulator of osteoblast function.

PMID- 22460932
TI  - Nanodiamonds in sugar rings: an experimental and theoretical investigation of
      cyclodextrin-nanodiamond inclusion complexes.
AB  - We report on the noncovalent interactions of nanodiamond carboxylic acids derived
      from adamantane, diamantane, and triamantane with beta- and gamma-cyclodextrins.
      The water solubility of the nanodiamonds was increased by attaching an aromatic
      dicarboxylic acid via peptide coupling. Isothermal titration calorimetry
      experiments were performed to determine the thermodynamic parameters (K(a),
      DeltaH, DeltaG and DeltaS) for the host-guest inclusion. The stoichiometry of the
      complexes is invariably 1:1. It was found that K(a), DeltaG and DeltaH of
      inclusion increase for larger nanodiamonds. DeltaS is generally positive, in
      particular for the largest nanodiamonds. beta-Cyclodextrin binds all
      nanodiamonds, gamma-cyclodextrin clearly prefers the most bulky nanodiamonds. The
      interaction of 9-triamantane carboxylic acid shows one of the strongest
      complexation constants towards gamma-cyclodextrin ever reported, K(a) = 5.0 *
      10(5) M(-1). In order to gain some insight into the possible structural basis of
      these inclusion complexes we performed density functional calculations at the B97
      D3/def2-TZVPP level of theory.

PMID- 22460940
TI  - Lack of recovery from hepatic oxidative damage in rats treated with Nigerian
      bonny light crude oil.
AB  - The use of Nigerian bonny light crude oil (BLCO) in the treatment of
      gastrointestinal disorders, burns, foot ulcers and reproductive capacity is a
      common practice in the southern part of Nigeria. Towards understanding the
      mechanism and the reversibility of hepatotoxicity induced by BLCO, adult male
      Wistar rats were orally administered with BLCO at 0, 50, 100 and 200 mg kg(-1)
      for 21 days. One-half of the rats were sacrificed on day 22, whereas the
      remaining half stayed for an additional 21 days without treatment. Whereas the
      activities of antioxidant enzymes such as superoxide dismutase, catalase,
      glutathione S-transferase were significantly (p < 0.05) increased, gamma glutamyl
      transferase activity was significantly decreased in a dose-dependent manner. The
      levels of glutathione, hydrogen peroxide and malondialdehyde were significantly
      elevated in BLCO-treated animals. In addition, hepatic degeneration was
      accompanied with elevation in serum aminotransferases activities without
      affecting bilirubin levels. Whereas most of the above-mentioned parameters were
      consistent in animals from withdrawal experiment, both total and conjugated
      bilirubin levels were significantly increased after 21 days of BLCO-treatment
      withdrawal. Taken together, BLCO-induced hepatotoxicity could be due to increased
      oxidative stress which was not reversible upon withdrawal of treatment within the
      time course of investigation in male rats.

PMID- 22460939
TI  - Cholinergic neurons in the mouse rostral ventrolateral medulla target sensory
      afferent areas.
AB  - The rostral ventrolateral medulla (RVLM) primarily regulates respiration and the
      autonomic nervous system. Its medial portion (mRVLM) contains many choline
      acetyltransferase (ChAT)-immunoreactive (ir) neurons of unknown function. We
      sought to clarify the role of these cholinergic cells by tracing their axonal
      projections. We first established that these neurons are neither parasympathetic
      preganglionic neurons nor motor neurons because they did not accumulate
      intraperitoneally administered Fluorogold. We traced their axonal projections by
      injecting a Cre-dependent vector (floxed-AAV2) expressing either GFP or mCherrry
      into the mRVLM of ChAT-Cre mice. Transduced neurons expressing GFP or mCherry
      were confined to the injection site and were exclusively ChAT-ir. Their axonal
      projections included the dorsal column nuclei, medullary trigeminal complex,
      cochlear nuclei, superior olivary complex and spinal cord lamina III. For control
      experiments, the floxed-AAV2 (mCherry) was injected into the RVLM of dopamine
      beta-hydroxylase-Cre mice. In these mice, mCherry was exclusively expressed by
      RVLM catecholaminergic neurons. Consistent with data from rats, these
      catecholaminergic neurons targeted brain regions involved in autonomic and
      endocrine regulation. These regions were almost totally different from those
      innervated by the intermingled mRVLM-ChAT neurons. This study emphasizes the
      advantages of using Cre-driver mouse strains in combination with floxed-AAV2 to
      trace the axonal projections of chemically defined neuronal groups. Using this
      technique, we revealed previously unknown projections of mRVLM-ChAT neurons and
      showed that despite their close proximity to the cardiorespiratory region of the
      RVLM, these cholinergic neurons regulate sensory afferent information selectively
      and presumably have little to do with respiration or circulatory control.

PMID- 22460941
TI  - Manual therapies for cervicogenic headache: a systematic review.
AB  - This paper systematically reviewed randomized clinical trials (RCT) assessing the
      efficacy of manual therapies for cervicogenic headache (CEH). A total of seven
      RCTs were identified, i.e. one study applied physiotherapy +/- temporomadibular
      mobilization techniques and six studies applied cervical spinal manipulative
      therapy (SMT). The RCTs suggest that physiotherapy and SMT might be an effective
      treatment in the management of CEH, but the results are difficult to evaluate,
      since only one study included a control group that did not receive treatment.
      Furthermore, the RCTs mostly included participant with infrequent CEH. Future
      challenges regarding CEH are substantial both from a diagnostic and management
      point of view.

PMID- 22460942
TI  - Refractory facial pain attributed to auriculotemporal neuralgia.

PMID- 22460943
TI  - Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double
      blind trial.
AB  - The objective and background is to confirm in a double-blind, placebo-controlled
      study the high triptan response rates we had previously reported in an open study
      in migraine patients with unilateral cranial autonomic symptoms. In this
      randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral
      cranial autonomic symptoms were assigned to receive rizatriptan 10 mg wafer or
      placebo (ratio 1:1) and treated for a single moderate or severe migraine attack.
      The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h.
      Secondary endpoints included pain relief, no associated symptoms and sustained
      pain freedom or relief. Significantly more patients reported pain freedom at 2 h
      after taking rizatriptan (54 %) than after placebo (8 %) (therapeutic gain 46 %
      [28 %; 64 %]; P < 0.001). Similarly, significantly more patients reported total
      migraine freedom at 2 h after rizatriptan (51 %) than after placebo (8 %)
      (therapeutic gain 43 % [26 %; 61 %]; P < 0.001). Rizatriptan was also more
      effective than placebo on most secondary endpoints. We confirm in a placebo
      controlled study our previous data suggesting that the presence of unilateral
      cranial autonomic symptoms in migraineurs predicts a positive response to
      triptans, probably owing to intense trigeminal peripheral afferent activation
      which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and
      preventive pharmacological trials in migraine should focus also on this subset of
      migraine patients.

PMID- 22460944
TI  - Migraine and behavior in children: influence of maternal headache frequency.
AB  - We took advantage of a large population study in order to measure child behavior,
      as captured by the Child Behavior Checklist (CBCL) as a function of headache
      status in the children and their mothers. Of the target sample, consents and
      analyzable data were obtained from 1,856 families (85.4 %). Headache diagnoses
      were defined according to the second edition of the International Classification
      of Headache Disorders, and behavioral and emotional symptoms were assessed by the
      validated Brazilian version of the CBCL. We calculated the relative risk of
      abnormalities in the CBCL domains as a function of headache status in the
      children, after adjusting by a series of main effect models. Children with
      migraine were more likely to present abnormal scores in several of the CBCL
      scales, relative to children without migraine, and maternal migraine status
      contributed little to the model. However, when the mother had daily headaches,
      both children with and without migraine had similar CBCL scores. In multivariate
      analyses, migraine status in the children predicted CBCL scores (p < 0.01).
      Headache status and headache frequency in the mother did not predict CBCL scores
      in children with migraine but predicted in children without migraine (p < 0.01).
      The burden of migraine to the family is complex. Children with migraine are more
      likely to have behavioral and emotional symptoms than children without migraine.
      Children without migraine may be affected, in turn, by frequent headaches
      experienced by their mothers.

PMID- 22460945
TI  - [Historical comments on urinary bladder catheterisation: an urological success
      story].
AB  - The first sounds and tubes were made of gold, bronze and tin or instruments made
      of reed, straw or rolled palm leaves. Over the course of the centuries the
      material as well as the design evolved because of the better knowledge of the
      anatomy of the human body. Especially French and German pioneers of the 19th and
      20th century with their new innovations led to the progress of the catheter. From
      the search of the right material, to the innovation of and appropriate fixation
      mechanism in the bladder. Only by continous promotion of the inventions over the
      turn of the time a perfect instrument made of the perfect material could evolve.

PMID- 22460946
TI  - A combined approach for beta-thalassemia based on gene therapy-mediated adult
      hemoglobin (HbA) production and fetal hemoglobin (HbF) induction.
AB  - Gene therapy might fall short in achieving a complete reversion of the beta
      thalassemic phenotype due to current limitations in vector design and
      myeloablative regimen. Following gene transfer, all or a large proportion of
      erythroid cells might express suboptimal levels of beta-globin, impairing the
      therapeutic potential of the treatment. Our aim was to evaluate whether, in
      absence of complete reversion of the beta-globin phenotype upon gene transfer, it
      is possible to use fetal hemoglobin induction to eliminate the residual alpha
      globin aggregates and achieve normal levels of hemoglobin. Transgenic K562 cell
      lines and erythroid precursor cells from beta(0)39-thalassemia patients were
      employed. Gene therapy was performed with the lentiviral vector T9W. Induction of
      fetal hemoglobin was obtained using mithramycin. Levels of mRNA and hemoglobins
      were determined by qRT-PCR and HPLC. First, we analyzed the effect of mithramycin
      on K562 transgenic cell lines harboring different copies of a lentiviral vector
      carrying the human beta-globin gene, showing that gamma-globin mRNA expression
      and HbF production can be induced in the presence of high levels of beta-globin
      gene expression and HbA accumulation. We then treated erythroid progenitor cells
      from beta-thalassemic patients with T9W, which expresses the human beta-globin
      gene and mithramycin separately or in combination. When transduction with our
      lentiviral vector is insufficient to completely eliminate the unpaired alpha
      globin chains, combination of beta-globin gene transfer therapy together with
      fetal hemoglobin induction might be very efficacious to remove the excess of
      alpha-globin proteins in thalassemic erythroid progenitor cells.

PMID- 22460947
TI  - Intensive consolidation therapy compared with standard consolidation and
      maintenance therapy for adults with acute myeloid leukaemia aged between 46 and
      60 years: final results of the randomized phase III study (AML 8B) of the
      European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo
      Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative
      Groups.
AB  - The most effective post-remission treatment to maintain complete remission (CR)
      in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is
      uncertain. Previously untreated patients with AML in CR after induction
      chemotherapy with daunorubicin and cytarabine were randomized between two
      intensive courses of consolidation therapy containing high-dose cytarabine,
      combined with amsacrine or daunorubicin and a standard consolidation and
      maintenance therapy containing standard dose cytarabine and daunorubicin. One
      hundred fifty-eight CR patients were assigned to the intensive group and 157
      patients to the standard group. After a median follow-up of 7.5 years, the 4-year
      survival rate was 32 % in the intensive group versus 34 % in the standard group
      (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than
      in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment
      related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive
      consolidation courses containing high-dose cytarabine as post-remission treatment
      in patients with AML aged between 46 and 60 years old did not translate in better
      long-term outcome despite a 20 % lower relapse incidence. Better supportive care
      and prevention of treatment-related complications may improve the overall
      survival after intensified post-remission therapy in this age group.

PMID- 22460948
TI  - The renal v-ATPase a4 subunit is expressed in specific subtypes of human gliomas.
AB  - Vacuolar H(+) -ATPases (v-ATPases) are multimeric proton pumps which acidify
      various intra-cellular organelles and may participate in pHe and pHi regulation
      in cancer cell lines. The ATP6V0A4 gene encodes the a4 subunit which is expressed
      in kidney and epididymis. Because we found a4 mRNA highly expressed in C6Bu1
      glioma cell line, we measured it in 205 glioma biopsies and 11 brain biopsies
      from epileptic patients. a4 was absent in epileptic brain biopsies, but was
      expressed by 34% (11/32) of grade III oligodendrogliomas, independently of the
      chromosome 1p19q codeletion. a4 expression in grade III oligodendrogliomas and
      oligoastrocytomas without the 1p19q codeletion tended to be associated with a
      shorter overall survival of patients. We also observed a4 expression in biopsies
      of pilocytic astrocytomas (68%; 19/28) and gangliogliomas (37%; 6/16). In
      pilocytic astrocytomas a4 expression was associated with a tandem duplication of
      the 7q34 chromosome region, distant 0.5 Mb to the ATP6V0A4 gene locus. In
      conclusion, a4 expression identifies subtypes of oligodendrogliomas, pilocytic
      astrocytomas and gangliogliomas and may contribute to refine characterization of
      these tumors. (c) 2012 Wiley Periodicals, Inc.

PMID- 22460949
TI  - Frequency discretization in dielectrophoretic assisted cell sorting arrays to
      isolate neural cells.
AB  - We present an automated dielectrophoretic assisted cell sorting (DACS) device for
      dielectric characterization and isolation of neural cells. Dielectrophoretic
      (DEP) principles are often used to develop cell sorting techniques. Here we
      report the first statistically significant neuronal sorting using DACS to enrich
      neurons from a heterogeneous population of mouse derived neural stem/progenitor
      cells (NSPCs) and neurons. We also study the dielectric dispersions within a
      heterogeneous cell population using a Monte-Carlo (MC) simulation. This
      simulation model explains the trapping behavior of populations as a function of
      frequency and predicts sorting efficiencies. The platform consists of a DEP
      electrode array with three multiplexed trapping regions that can be independently
      activated at different frequencies. A novel microfluidic manifold enables cell
      sorting by trapping and collecting cells at discrete frequency bands rather than
      single frequencies. The device is used to first determine the percentage of cells
      trapped at these frequency bands. With this characterization and the MC
      simulation we choose the optimal parameters for neuronal sorting. Cell sorting
      experiments presented achieve a 1.4-fold neuronal enrichment as predicted by our
      model.

PMID- 22460950
TI  - Physics and engineering of peptide supramolecular nanostructures.
AB  - The emerging "bottom-up" nanotechnology reveals a new field of bioinspired
      nanomaterials composed of chemically synthesized biomolecules. They are formed
      from elementary constituents in supramolecular structures by the use of a
      developed nature self-assembly mechanism. The focus of this perspective paper is
      on intrinsic fundamental physical properties of bioinspired peptide
      nanostructures and their small building units linked by weak noncovalent bonds.
      The observed exceptional optical properties indicate a phenomenon of quantum
      confinement in these supramolecular structures, which originates from nanoscale
      size of their elementary building blocks. The dimensionality of the confinement
      gives insight into intrinsic packing of peptide supramolecular nanomaterials. QC
      regions, revealed in bioinspired nanostructures, were found by us in amyloid
      fibrils formed from insulin protein. We describe ferroelectric and related
      properties found at the nanoscale based on original crystalline asymmetry of the
      nanoscale building blocks, packing these structures. In this context, we reveal a
      classic solid state physics phenomenon such as reconstructive phase transition
      observed in bioorganic peptide nanotubes. This irreversible phase transformation
      leads to drastic reshaping of their quantum structure from quantum dots to
      quantum wells, which is followed by variation of their space group symmetry from
      asymmetric to symmetric. We show that the supramolecular origin of these
      bioinspired nanomaterials provides them a unique chance to be disassembled into
      elementary building block peptide nanodots of 1-2 nm size possessing unique
      electronic, optical and ferroelectric properties. These multifunctional nanounits
      could lead to a new future step in nanotechnology and nanoscale advanced devices
      in the fields of nanophotonics, nanobiomedicine, nanobiopiezotronics, etc.

PMID- 22460951
TI  - Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.
AB  - Synchronizing rhythms of behaviour and metabolic processes is important for
      cardiovascular health and preventing metabolic diseases. The nuclear receptors
      REV-ERB-alpha and REV-ERB-beta have an integral role in regulating the expression
      of core clock proteins driving rhythms in activity and metabolism. Here we
      describe the identification of potent synthetic REV-ERB agonists with in vivo
      activity. Administration of synthetic REV-ERB ligands alters circadian behaviour
      and the circadian pattern of core clock gene expression in the hypothalami of
      mice. The circadian pattern of expression of an array of metabolic genes in the
      liver, skeletal muscle and adipose tissue was also altered, resulting in
      increased energy expenditure. Treatment of diet-induced obese mice with a REV-ERB
      agonist decreased obesity by reducing fat mass and markedly improving
      dyslipidaemia and hyperglycaemia. These results indicate that synthetic REV-ERB
      ligands that pharmacologically target the circadian rhythm may be beneficial in
      the treatment of sleep disorders as well as metabolic diseases.

PMID- 22460955
TI  - Should we abandon vancomycin for treatment of methicillin-resistant
      Staphylococcus aureus pneumonia? Still questions to answer.

PMID- 22460952
TI  - Regulation of circadian behaviour and metabolism by REV-ERB-alpha and REV-ERB
      beta.
AB  - The circadian clock acts at the genomic level to coordinate internal behavioural
      and physiological rhythms via the CLOCK-BMAL1 transcriptional heterodimer.
      Although the nuclear receptors REV-ERB-alpha and REV-ERB-beta have been proposed
      to form an accessory feedback loop that contributes to clock function, their
      precise roles and importance remain unresolved. To establish their regulatory
      potential, we determined the genome-wide cis-acting targets (cistromes) of both
      REV-ERB isoforms in murine liver, which revealed shared recognition at over 50%
      of their total DNA binding sites and extensive overlap with the master circadian
      regulator BMAL1. Although REV-ERB-alpha has been shown to regulate Bmal1
      expression directly, our cistromic analysis reveals a more profound connection
      between BMAL1 and the REV-ERB-alpha and REV-ERB-beta genomic regulatory circuits
      than was previously suspected. Genes within the intersection of the BMAL1, REV
      ERB-alpha and REV-ERB-beta cistromes are highly enriched for both clock and
      metabolic functions. As predicted by the cistromic analysis, dual depletion of
      Rev-erb-alpha and Rev-erb-beta function by creating double-knockout mice
      profoundly disrupted circadian expression of core circadian clock and lipid
      homeostatic gene networks. As a result, double-knockout mice show markedly
      altered circadian wheel-running behaviour and deregulated lipid metabolism. These
      data now unite REV-ERB-alpha and REV-ERB-beta with PER, CRY and other components
      of the principal feedback loop that drives circadian expression and indicate a
      more integral mechanism for the coordination of circadian rhythm and metabolism.

PMID- 22460956
TI  - A potential "blind spot" in vancomycin treatment studies.

PMID- 22460957
TI  - Improved virological outcome in non-B patients: a possible role for baseline
      coreceptor tropism.

PMID- 22460958
TI  - Linezolid for the treatment of nosocomial pneumonia due to methicillin-resistant
      Staphylococcus aureus.

PMID- 22460959
TI  - Questionable superiority of linezolid for methicillin-resistant Staphylococcus
      aureus nosocomial pneumonia: watch where you step.

PMID- 22460960
TI  - Linezolid versus vancomycin for methicillin-resistant Staphylococcus aureus
      nosocomial pneumonia: controversy continues.

PMID- 22460962
TI  - Development of tropical spastic paraparesis in human T-lymphotropic virus type 1
      carriers is influenced by interleukin 28B gene polymorphisms.
AB  - Interleukin 28B (IL28B) rs12979860 polymorphisms were examined in 41 individuals
      with human T-lymphotrophic virus type 1 (HTLV-1). The alleles CT/TT were more
      frequent in 12 individuals with HTLV-1-associated myelopathy/tropical spastic
      paraparesis than in 29 asymptomatic carriers (80% vs 20%; P = .03), and median
      HTLV-1 proviral load was greater in CT/TT than CC carriers (P = .01). Thus, IL28B
      testing and closer follow-up of HTLV-1 asymptomatic CT/TT carriers is warranted.

PMID- 22460963
TI  - Discordance between CD4+ T-lymphocyte counts and percentages in HIV-infected
      persons with liver fibrosis.
AB  - BACKGROUND: Cirrhosis of the liver can induce splenic sequestration of peripheral
      blood cells, recently suggested to reduce the number but not percentage of
      circulating CD4(+) T cells in persons uninfected with human immunodeficiency
      virus (HIV). We investigated whether earlier stages of liver fibrosis prior to
      cirrhosis were associated with discordance between CD4 count (CD4N) and CD4
      percentage (CD4%) in HIV-infected patients. METHODS: In cross-sectional analysis
      of 287 HIV-infected participants of the AIDS Linked to the Intravenous Experience
      cohort, we evaluated CD4N, CD4%, and transient elastography staging of liver
      fibrosis. High CD4(+) lymphocyte discordance was defined as higher CD4% relative
      to CD4N based on accepted clinical cutoffs; multivariable logistic regression was
      used to determine covariates associated with discordance. RESULTS: Of 287
      participants, 99 (34.4%) had high CD4(+) discordance, which increased to 76% of
      114 participants with marked lymphopenia (total lymphocyte count [TLC] <=1200
      cells/MUL). In multivariable analysis, the odds of having high CD4(+) discordance
      was increased in persons with significant liver fibrosis compared to those
      without fibrosis (odds ratio, 1.69; 95% confidence interval [CI], .95-2.96); the
      odds ratio of discordance increased to 2.66 (95% CI, 1.11-6.40) among the subset
      of participants with TLC <=1200 cells/MUL. The odds for discordance associated
      with cirrhosis were of similar magnitude as those observed with significant
      fibrosis. CONCLUSIONS: In HIV-infected persons, liver fibrosis is associated with
      discordant peripheral CD4(+) lymphocyte results, especially in the setting of
      marked lymphopenia. Clinicians should also consider CD4% when interpreting
      absolute CD4(+) counts of HIV-infected persons with known or suspected liver
      disease, particularly if TLC is <1200 cells/MUL.

PMID- 22460964
TI  - Factors associated with discordance between absolute CD4 cell count and CD4 cell
      percentage in patients coinfected with HIV and hepatitis C virus.
AB  - BACKGROUND: Liver cirrhosis has been associated with decreased absolute CD4 cell
      counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)
      negative persons. We evaluated factors associated with discordance between the
      absolute CD4 cell count and the CD4 cell percentage in a cohort of patients
      coinfected with HIV and hepatitis C virus (HCV). METHODS: Baseline data from 908
      participants in a prospective, Canadian, multisite cohort of individuals with HIV
      HCV coinfection were analyzed. Absolute CD4 cell count and CD4 cell percentage
      relationships were evaluated. We defined low and high discordance between
      absolute CD4 cell count/CD4 cell percentage relationships as CD4 cell percentages
      that differed from the expected CD4 cell percentage, given the observed absolute
      CD4 cell count, by +/-7 percentage points; we defined very low and very high
      discordance as differences of +/-14 percentage points. Factors associated with
      high or very high discordance, including either end-stage liver disease or
      aspartate transaminase to platelet ratio index (APRI) of >1.5, were analyzed
      using multivariate logistic regression models and compared to groups with
      concordant and low discordant results. RESULTS: High/very high discordance was
      seen in 31% (n = 286), while 35% (n = 321) had concordant values. Factors
      associated with very high discordance at baseline included history of end-stage
      liver disease (adjusted odds ratio [aOR], 6.52; 95% confidence interval [CI],
      2.27-18.67) and APRI of >1.5 (aOR 4.69; 95% CI, 1.64-13.35). Compared with those
      with detectable HCV RNA, those who cleared HCV spontaneously were less likely to
      have very high discordance. CONCLUSIONS: Discordance between absolute CD4 cell
      count and CD4 cell percentage is common in an HIV/HCV-coinfected population and
      is associated with advanced liver disease and ongoing HCV replication.

PMID- 22460965
TI  - Emergency department visit rates for abscess versus other skin infections during
      the emergence of community-associated methicillin-resistant Staphylococcus
      aureus, 1997-2007.
AB  - Due to a flaw in the International Classification of Diseases, Ninth Revision,
      Clinical Modification coding system, epidemiology of skin and soft-tissue
      infections (SSTIs) has conflated abscess with other SSTIs. We analyzed emergency
      department visits during 1997-2007, finding that the odds of abscess relative to
      any other diagnosis increased 11% per year, or 3.1-fold, whereas other SSTIs
      increased minimally.

PMID- 22460966
TI  - Long-term valacyclovir suppressive treatment after herpes simplex virus type 2
      meningitis: a double-blind, randomized controlled trial.
AB  - BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a common cause of acute and
      recurrent aseptic meningitis. Our aim was to determine the impact of antiviral
      suppression on recurrence of meningitis and to delineate the full spectrum of
      neurological complications. METHODS: One hundred and one patients with acute
      primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g
      of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g
      of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled,
      multicenter trial. The primary outcome was time until recurrence of meningitis.
      The patients were followed up for 2 years. RESULTS: The first year, no
      significant difference was found between the valacyclovir and placebo groups. The
      second year, without study drugs, the risk of recurrence of verified and probable
      HSV-2 meningitis was significantly higher among patients exposed to valacyclovir
      (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the
      patients experienced 1-4 meningitis episodes during the study period. A
      considerable morbidity rate, comprising symptoms from the central, peripheral,
      and autonomous nervous system, was found in both groups. CONCLUSIONS: Suppressive
      treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit
      recurrent meningitis and cannot be recommended for this purpose after HSV
      meningitis in general. Protection against mucocutaneous lesions was observed, but
      the dosage was probably inappropriate for the prevention of HSV activation in the
      central nervous system. The higher frequency of meningitis, after cessation of
      active drug, could be interpreted as a rebound phenomenon.

PMID- 22460968
TI  - Oseltamivir and its active metabolite cross the placenta at significant levels.

PMID- 22460967
TI  - Long-term outcome of patients presenting with acute infectious encephalitis of
      various causes in France.
AB  - BACKGROUND: A prospective study of infectious encephalitis was conducted in
      France in 2007. In total, 253 patients were enrolled with a proven etiological
      diagnosis for 52%. The cohort of surviving patients with encephalitis was
      assessed for sequelae and impairment 3 years after enrollment. METHODS: Patients,
      their family, and general practitioners (GPs) were interviewed by phone to
      document persisting symptoms, return to work, and past and current leisure
      activities, with standardized questionnaires. The IQCODE (Informant Questionnaire
      on Cognitive Decline in the Elderly) was completed with relatives. The global
      outcome was determined in all patients with the Glasgow outcome scale. RESULTS:
      In 2010, 20 patients (10%) were unavailable for follow-up, 2 (1%) were excluded,
      and 18 (9%) had died since hospital discharge. Data were available for 167
      survivors and 9 patients whose death was related to the encephalitis. The outcome
      was favorable in 108 of 176 patients (61%) (71 with complete resolution), 31
      (18%) were mildly impaired, 25 (14%) were severely impaired, and 3 (1%) were in a
      vegetative state. The most frequent symptoms were difficulty concentrating (42%),
      behavioral disorders (27%), speech disorders (20%), and memory loss (19%).
      Fifteen of 63 patients (24%) previously employed were still unable to resume
      work. Long-term outcome was significantly associated with comorbid conditions,
      age, level of education, and the causative agent of encephalitis. CONCLUSIONS:
      Most patients with encephalitis experienced a favorable outcome 3 years after
      hospital discharge. However, minor to severe disability persists in a high number
      of cases with consequences for everyday life. Physical and mental impairment
      should be evaluated in all patients with encephalitis, and neuropsychological
      rehabilitation implemented whenever needed.

PMID- 22460969
TI  - Premature delivery in HIV-infected women starting protease inhibitor therapy
      during pregnancy: role of the ritonavir boost?
AB  - BACKGROUND: The association between combination antiretroviral (cARV) therapy use
      by human immunodeficiency virus (HIV)-infected women during pregnancy and risk of
      prematurity is still controversial. We explored this question, focusing on the
      initiation of ritonavir-boosted protease inhibitors (PIs) during pregnancy, which
      is now standard care. METHODS: Trends in prematurity (<37 gestational weeks) were
      studied among all singleton pregnancies in the Agence Nationale de Recherche sur
      le SIDA (ANRS) French Perinatal Cohort from 1990 through 2009 (n = 13 271). In
      depth analysis was conducted in a more detailed substudy of the cohort, among
      women starting PI-based ARV therapy during pregnancy (n = 1253). Multivariable
      analysis adjusted for immunovirological status and known risk factors for
      prematurity. RESULTS: Prematurity increased from 9.2% during 1990-1993 (no
      therapy) and 9.6% during 1994-1996 (mostly zidovudine monotherapy) to 12.4%
      during 1997-1999 (dual-nucleoside analog therapy) and 14.3% during 2005-2009
      (routine cARV therapy; P < .01). Prematurity was associated with cARV therapy,
      compared with zidovudine monotherapy, with an adjusted odds ratio of 1.69 (95%
      confidence interval [CI], 1.38-2.07; P < .01) when accounting for maternal age,
      intravenous drug use, geographic origin, and CD4 cell count. During 2005-2009,
      the prematurity rate was higher with boosted than with nonboosted PI therapy
      started during pregnancy (14.4% vs 9.1% [P = .05]; adjusted hazard ratio, 2.03
      [95% CI, 1.06-3.89; P = .03] in multivariate analysis). The difference concerned
      mainly induced preterm delivery for maternal or fetal indications (5.6% vs 1.6%;
      P = .02), CONCLUSIONS: The prematurity rate among HIV-infected pregnant women was
      twice that in the general population in France; this was not entirely explained
      by sociodemographic characteristics. Prematurity was independently associated
      with cARV therapy and, particularly, with the initiation of ritonavir-boosted PI
      therapy during pregnancy.

PMID- 22460970
TI  - Validation of clinical scores for risk assessment.

PMID- 22460972
TI  - Pneumonia in the community caused by multidrug-resistant organisms: keep working
      on probabilistic scores.

PMID- 22460973
TI  - A new piece in the puzzle of antiretroviral therapy in pregnancy and preterm
      delivery risk.

PMID- 22460975
TI  - Increasingly successful highly active antiretroviral therapy delays the emergence
      of new HLA class I-associated escape mutations in HIV-1.
AB  - BACKGROUND: HLA class I-restricted cytotoxic T lymphocytes and highly active
      antiretroviral therapy (HAART) exert strong selective pressures on human
      immunodeficiency virus type 1 (HIV-1), leading to escape mutations compromising
      virologic control. Immune responses continue to shape HIV-1 evolution after HAART
      initiation, but the extent and rate at which this occurs remain incompletely
      quantified. Here, we characterize the incidence and clinical correlates of HLA
      associated evolution in HIV-1 Pol after HAART initiation in a large, population
      based observational cohort. METHODS: British Columbia HAART Observational,
      Medical Evaluation and Research cohort participants with available HLA class I
      types and longitudinal posttherapy protease/reverse transcriptase sequences were
      studied (n = 619; median, 5 samples per patient and 5.2 years of follow-up). HLA
      associated polymorphisms were defined according to published reference lists.
      Rates and correlates of immune-mediated HIV-1 evolution were investigated using
      multivariate Cox proportional hazard models incorporating baseline and time
      dependent plasma viral load and CD4 response data. RESULTS: New HLA-associated
      escape events were observed in 269 (43%) patients during HAART and occurred at 49
      of 63 (78%) investigated immune-associated sites in Pol. In time-dependent
      analyses adjusting for baseline factors, poorer virologic, but not immunologic,
      response to HAART was associated with increased risk of immune escape of 1.9-fold
      per log(10) viral load increment (P < .0001). Reversion of escape mutations
      following HAART initiation was extremely rare. CONCLUSIONS: HLA-associated HIV-1
      evolution continues during HAART to an extent that is inversely related to the
      virologic success of therapy. Minimizing the degree of immune escape could
      represent a secondary benefit of effective HAART.

PMID- 22460976
TI  - Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with
      organic fenugreek sprouts, France, June 2011.
AB  - BACKGROUND: On 22 June 2011, 8 patients with hemolytic uremic syndrome (HUS) or
      bloody diarrhea were reported in France. All 8 were attendees of a community
      center event on 8 June near Bordeaux. Three Escherichia coli cases were confirmed
      by isolation of Shiga toxin-producing E. coli O104:H4 stx2 aggR producing a
      cefotaximase (CTX-M) beta-lactamase (STEC O104:H4); the same rare serotype caused
      the outbreak in Germany in May-July 2011. An investigation was initiated to
      describe the outbreak, identify the vehicle for infection, and guide control
      measures. METHODS: We conducted a retrospective cohort study among all adults
      attending the event, including food handlers. A standardized questionnaire was
      administered to participants. A case was an attendee who developed HUS or
      diarrhea between 8 and 24 June. Cases were confirmed by isolation of STEC O104:H4
      or O104 serology. Relative risks (RRs) and 95% confidence intervals (CIs) by
      exposure were calculated using a Poisson regression model. RESULTS: Twenty-four
      cases were identified (14% attack rate). Of these, 18 (75%) were women, 22 (92%)
      were adults, 7 (29%) developed HUS, 5 (21%) developed bloody diarrhea, and 12
      (50%) developed diarrhea. Ten (42%) cases were confirmed. Fenugreek was the only
      sprout type with an independent association to illness (RR, 5.1; 95% CI, 2.3
      11.1) in multivariable analysis. CONCLUSIONS: This investigation identified a
      point-source STEC O104:H4 outbreak associated with consumption of fenugreek
      sprouts. Comparison of results from French and German STEC O104:H4 outbreak
      investigations enabled identification of a common food vehicle, fenugreek
      sprouts, and resulted in implementation of Europe-wide control measures in July
      2011.

PMID- 22460977
TI  - Daptomycin or vancomycin for methicillin-resistant Staphylococcus aureus with a
      vancomycin minimum inhibitory concentration >1 MUg/L.

PMID- 22460979
TI  - Airborne transmission of influenza: implications for control in healthcare and
      community settings.

PMID- 22460980
TI  - Efficacy of rapid treatment initiation following primary Toxoplasma gondii
      infection during pregnancy.
AB  - BACKGROUND: Treatment of Toxoplasma gondii infection acquired during pregnancy
      differs in many countries. In Germany, spiramycin is given until the 16th week of
      pregnancy, followed by at least 4 weeks of combination therapy with
      pyrimethamine, sulfadiazine, and folinic acid independent of the infection stage
      of the fetus. If infection of the fetus is confirmed by polymerase chain reaction
      or if fetal ultrasound indicates severe symptoms (hydrocephalus, ventricular
      dilation), treatment is continued until delivery with regular monitoring of
      pyrimethamine and sulfadiazine concentration in maternal blood and observation of
      possible adverse effects. In other European countries, such as France, only
      spiramycin is given unless infection of the fetus is proven. METHODS: To evaluate
      the effectiveness of the German treatment scheme, a retrospective analysis of 685
      women who showed a serological constellation consistent with primary infection in
      pregnancy and their children was performed. RESULTS: We found an increased
      transmission rate to the fetus with increased time in gestation and a decreased
      risk of clinical manifestations. In comparison with studies performed in other
      countries, the overall transmission rate (4.8%) and the rate of clinical
      manifestations in newborns (1.6%) were lower. CONCLUSIONS: Use of spiramycin from
      time of diagnosis of acute acquisition of infection by the pregnant woman until
      week 16, followed by pyrimethamine, sulfadiazine, and folinic acid for at least 4
      weeks in combination with a standardized follow-up program is efficient in
      reducing transplacental transmission of the parasite and the burden of disease in
      the newborn.

PMID- 22460982
TI  - Ontogenetic influence on neural spine bifurcation in Diplodocoidea (Dinosauria:
      Sauropoda): a critical phylogenetic character.
AB  - Within Diplodocoidea (Dinosauria: Sauropoda), phylogenetic position of the three
      subclades Rebbachisauridae, Dicraeosauridae, and Diplodocidae is strongly
      influenced by a relatively small number of characters. Neural spine bifurcation,
      especially within the cervical vertebrae, is considered to be a derived
      character, with taxa that lack this feature regarded as relatively basal. Our
      analysis of dorsal and cervical vertebrae from small-sized diplodocoids
      (representing at least 18 individuals) reveals that neural spine bifurcation is
      less well developed or absent in smaller specimens. New preparation of the
      roughly 200-cm long diplodocid juvenile Sauriermuseum Aathal 0009 reveals simple
      nonbifurcated cervical neural spines, strongly reminiscent of more basal
      sauropods such as Omeisaurus. An identical pattern of ontogenetically linked
      bifurcation has also been observed in several specimens of the basal macronarian
      Camarasaurus, suggesting that this is characteristic of several clades of
      Sauropoda. We suggest that neural spine bifurcation performs a biomechanical
      function related to horizontal positioning of the neck that may become
      significant only at the onset of a larger body size, hence, its apparent absence
      or weaker development in smaller specimens. These results have significant
      implications for the taxonomy and phylogenetic position of taxa described from
      specimens of small body size. On the basis of shallow bifurcation of its cervical
      and dorsal neural spines, the small diplodocid Suuwassea is more parsimoniously
      interpreted as an immature specimen of an already recognized diplodocid taxon.
      Our findings emphasize the view that nonmature dinosaurs often exhibit
      morphologies more similar to their ancestral state and may therefore occupy a
      more basal position in phylogenetic analyses than would mature specimens of the
      same species. In light of this, we stress the need for phylogenetic reanalysis of
      sauropod clades where vital characters may be ontogenetically variable,
      particularly when data is derived from small individuals.

PMID- 22460981
TI  - Detection of infectious influenza virus in cough aerosols generated in a
      simulated patient examination room.
AB  - BACKGROUND: The potential for aerosol transmission of infectious influenza virus
      (ie, in healthcare facilities) is controversial. We constructed a simulated
      patient examination room that contained coughing and breathing manikins to
      determine whether coughed influenza was infectious and assessed the effectiveness
      of an N95 respirator and surgical mask in blocking transmission. METHODS:
      National Institute for Occupational Safety and Health aerosol samplers collected
      size-fractionated aerosols for 60 minutes at the mouth of the breathing manikin,
      beside the mouth, and at 3 other locations in the room. Total recovered virus was
      quantitated by quantitative polymerase chain reaction and infectivity was
      determined by the viral plaque assay and an enhanced infectivity assay. RESULTS:
      Infectious influenza was recovered in all aerosol fractions (5.0% in >4 MUm
      aerodynamic diameter, 75.5% in 1-4 MUm, and 19.5% in <1 MUm; n = 5). Tightly
      sealing a mask to the face blocked entry of 94.5% of total virus and 94.8% of
      infectious virus (n = 3). A tightly sealed respirator blocked 99.8% of total
      virus and 99.6% of infectious virus (n = 3). A poorly fitted respirator blocked
      64.5% of total virus and 66.5% of infectious virus (n = 3). A mask documented to
      be loosely fitting by a PortaCount fit tester, to simulate how masks are worn by
      healthcare workers, blocked entry of 68.5% of total virus and 56.6% of infectious
      virus (n = 2). CONCLUSIONS: These results support a role for aerosol transmission
      and represent the first reported laboratory study of the efficacy of masks and
      respirators in blocking inhalation of influenza in aerosols. The results indicate
      that a poorly fitted respirator performs no better than a loosely fitting mask.

PMID- 22460983
TI  - Growth charts suitable for Indian children--an unending saga?

PMID- 22460984
TI  - Is therapeutic hypothermia real cause of subcutaneous fat necrosis in newborns?

PMID- 22460986
TI  - Unusual skin manifestation of antiphospholipid syndrome.

PMID- 22460985
TI  - Experimental model of arthritis induced by Paracoccidioides brasiliensis in rats.
AB  - Paracoccidioidomycosis (PCM), a disease caused by the fungus Paracoccidioides
      brasiliensis (Pb), is highly prevalent in Brazil, where it is the principal cause
      of death by systemic mycoses. The disease primarily affects men aged 30-50 year
      old and usually starts as a pulmonary focus and then may spread to other organs
      and systems, including the joints. The present study aimed to develop an
      experimental model of paracoccidioidomycotic arthritis. Two-month-old male Wistar
      rats (n = 48) were used, divided in 6 groups: test groups EG/15 and EG/45
      (received one dose of 100 MUl of saline containing 10(5) Pb viable yeasts in the
      knee); heat killed Pb-group HK/15 and HK/45 (received a suspension of 10(5) Pb
      nonviable yeasts in the knee) and control groups CG/15 and CG/45 (received only
      sterile saline in the knee). The rats were killed 15 and 45 days postinoculation.
      In contrast with the control rats, the histopathology of the joints of rats of
      the test groups (EG/15 and EG/45) revealed a picture of well-established PCM
      arthritis characterized by extensive sclerosing granulomatous inflammation with
      numerous multiple budding fungal cells. The X-ray examination revealed joint
      alterations in these groups. Only metabolic active fungi evoked inflammation. The
      experimental model was able to induce fungal arthritis in the knees of the rats
      infected with metabolic active P. brasiliensis. The disease tended to be
      regressive and restrained by the immune system. No evidence of fungal
      dissemination to the lungs was observed.

PMID- 22460987
TI  - A difficult diagnosis to SPOT.

PMID- 22460988
TI  - From the Editor-in-Chief.

PMID- 22460989
TI  - Epidemiology of urolithiasis: an update.
AB  - Background & Aim. Changing socio-economic conditions generated changes in the
      prevalence, incidence and distribution for age, sex and type of urolithiasis in
      terms of both the site and the chemical-physical composition of the calculi.In
      the latter part of the 20(th) century the prevalence of upper urinary tract
      stones was increasing in Western countries whereas endemic infantile bladder
      stone disease was fairly widespread in huge areas of developing countries. The
      aim of this paper was to update previous epidemiological reports of urolithiasis
      by reviewing the more recent literature.Methods. Citations were extracted using
      PubMed database from January 2003 through December 2007 on the basis of the key
      words epidemiology AND urinary calculi. Results. An increase in the prevalence
      and incidence of urolithiasis was described in Germany whereas data from the
      United States were contradictory with stone disease rates increased only for
      women with a change of male-to-female ratio. Prevalence figures of stone disease
      observed in some developing country in tropical regions were similar to rates of
      Western countries with incidence of renal colic particularly high in warm months.
      African Americans had a reduced risk of stone disease compared to other racial
      groups but in renal stone patients all racial groups demonstrated a similarity in
      the incidence of underlying metabolic abnormalities. Upper urinary tract stones
      in children were associated more frequently with metabolic disturbances rather
      than with urinary tract anomalies and infection. Endemic childhood bladder stones
      are still present in some developing countries.Dietary risk factors for stone
      disease were shown different by age and sex. In particular in younger women
      dietary calcium, phytate and fluid intake were associated with a reduced risk of
      stone formation whereas animal protein and sucrose increased the risk of stone
      incidence. In older adults there was no association between dietary calcium and
      stone formation whereas magnesium, potassium and fluid intakes decreased and
      total vitamin C intake increased the risk of symptomatic nephrolithiasis. Animal
      protein was associated with risk only in men with a body mass index < 25 kg/m(2).
      Type 2 diabetes and several other coronary heart disease risk factors, including
      hypertension and obesity are associated with nephrolithiasis.

PMID- 22460990
TI  - Pathogenesis of nephrolithiasis: recent insight from cell biology and renal
      pathology.
AB  - Randall's plaques are very common in idiopathic calcium-oxalate nephrolithiasis.
      These papillary plaques have an apatite mineral structure. While these calcium
      deposits are generally assumed to be secondary to a purely physico-chemical
      phenomenon, we advance the hypothesis that they form due to a truly ectopic
      biomineralization in the renal tissue, and that Henle's loop epithelial cells, or
      pericyte-like interstitial cells, or papillary stem cells differentiating along a
      bone lineage might be involved.

PMID- 22460991
TI  - Update on the genetics of nephrolithiasis.
AB  - Genetic studies of calcium kidney stones evidenced the possible involvement of
      calcium-sensing receptor gene, vitamin D receptor gene and bicarbonate-sensitive
      adenylate cyclase gene, but it is uncertain which specific polymorphisms could be
      responsible. Thus, further studies are required to better assess the involvement
      of these or other genes and the interactions between different genes and between
      genes and environment. In addition to research in humans, the study of different
      strains of knock-out mice let us include the gene of phosphate reabsorption
      carrier NPT2, caveolin-1, protein NHERF-1, osteopontin and Tamm-Horsfall protein
      among the possible determinants. Further steps in the knowledge of calcium stone
      causes may be done using the instruments that the modern biotechnology and
      bioinformatics have made available to the researchers.

PMID- 22460994
TI  - Biochemical evaluation in renal stone disease.
AB  - Renal stone disease may ensue from either derangements of urine biochemistries or
      anatomic abnormalities of kidneys and urinary tract. Genetic, environmental and
      dietary factors may also cooperate in the pathophysiology of nephrolithiasis. An
      adequate metabolic evaluation should focus on the urinary excretion of promoters
      and inhibitors of stone formation as well as on the occurrence of systemic
      diseases potentially related to secondary nephrolithiasis (i.e., endocrine
      disturbances, malabsorption, bone diseases). Moreover, metabolic investigations
      should provide reliable information on patient's dietary habits, guide towards
      the best therapeutic approach and enable the physician to verify patient's
      compliance to prescribed therapies.AN EXTENSIVE METABOLIC EVALUATION IS
      RECOMMENDED IN PATIENTS WITH ACTIVE STONE DISEASE (NAMELY, AT LEAST ONE NEW STONE
      WITHIN THE LAST TWO YEARS), OR IN THOSE HAVING HAD A SINGLE STONE EPISODE
      OCCURRED IN PECULIAR CONDITIONS: familial history of disease, childhood,
      menopause, pregnancy, systemic diseases. Simplified protocols may be adequate in
      non-active nephrolithiasis or in patients with single stone and no relevant risk
      factors.In our Stone Centre, a so-called "first level screening" is performed by
      routine, in order to assess urinary supersaturation with stone forming salts and
      evaluate the excretion of dietary-related metabolites in urine. Relative blood
      and urine determinations are reported below.IN VENOUS BLOOD: urea, creatinine,
      uric acid, Na, K, total and ionised Ca, Mg, P, Cl, alkaline phosphatase, gas
      analysis. In 24-hr urine samples: urea, creatinine, uric acid, Na, K, Ca, Mg, P,
      Cl, oxalate, inorganic sulphate, citrate, pH, ammonia and titratable acidity. IN
      FASTING URINE SAMPLES: Ca, citrate, creatinine, hydroxyproline, Brand's test for
      cistinuria, urine sediment, urine culture. If the first-level evaluation
      suggested an abnormal bone turnover, then further determinations are warranted,
      namely, calciotropic hormones (blood Vitamin D and PTH), markers of bone
      resorption (urine pyridinium crosslinks, serum crosslaps) and formation (serum
      osteocalcin) bone mineral density.EVENTUALLY, MORE SOPHISTICATED INVESTIGATIONS
      ARE REQUIRED TO IMPROVE THE DIAGNOSIS OF PECULIAR DISEASES: serum oxalate and
      glycolate, urine glycolate and L-glycerate, hepatic AGT activity (primary
      hyperoxalurias); genetic tests (hereditary nephrolithiasis); acidification tests
      (renal tubular acidosis).

PMID- 22460992
TI  - Metabolic syndrome and nephrolithiasis: can we hypotize a common background?
AB  - Metabolic syndrome and nephrolithiasis are quite common disorders presenting
      similar epidemiological characteristics. Belonging to genetic, environmental and
      hormonal interaction, they have high incidence and prevalence in the adult
      population of industrialised countries and are characterised by a high level of
      morbidity and mortality if not adequately identified and treated. Despite
      metabolic syndrome is considered a fundamental risk factor for chronic kidney
      diseases, is not actually known whether it is associated with nephrolithiasis
      beyond the effect of its individual components, in particular obesity, glucose
      intolerance, and hypertension. In this paper, the possible pathogenetic links
      between metabolic syndrome and nephrolithiasis will be presented and discussed.

PMID- 22460993
TI  - Bone disease in primary hypercalciuria.
AB  - Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone
      demineralization. The most frequent clinical condition in which this association
      has been observed is calcium nephrolithiasis. In patients affected by this
      disorder bone density is very frequently low and increased susceptibility to
      fragility fractures is reported. The very poor definition of this bone disease
      from a histomorphometric point of view is a crucial aspect. At present, the most
      common finding seems to be a low bone turnover condition. Many factors are
      involved in the complex relationships between bone loss and PH. Since bone loss
      was mainly reported in patients with fasting hypercalciuria, a primary alteration
      in bone metabolism was proposed as a cause of both hypercalciuria and bone
      demineralization. This hypothesis was strengthened by the observation that some
      bone resorbing-cytokines, such as IL-1, IL-6, and TNF-alpha are high in
      hypercalciuric patients. The effect of an excessive response to the acid load
      induced by dietary protein intake seems an additional factor explaining a
      primitive alteration of bone. The intestine plays a major role in the clinical
      course of bone disease in PH. Patients with absorptive hypercalciuria less
      frequently show bone disease and a reduction in dietary calcium greatly increases
      the probability of bone loss in PH subjects. It has recently been reported that
      greater bone loss is associated with a larger increase in intestinal calcium
      absorption in PH patients. Considering the absence of PTH alterations, it was
      proposed that this is not a compensatory phenomenon, but probably the marker of
      disturbed cell calcium transport, involving both intestinal and bone tissues.
      While renal hypercalciuria is rather uncommon, the kidney still seems to play a
      role in the pathogenesis of bone loss of PH patients, possibly via the effect of
      mild to moderate urinary phosphate loss with secondary hypophosphatemia. In
      conclusion, bone loss is very common in PH patients. Even if most of the factors
      involved in this process have been identified, many aspects of this intriguing
      clinical condition remain to be elucidated.

PMID- 22460995
TI  - Use of drugs for nephrolithiasis.
AB  - Renal stone disease often begins by renal colic. In order to manage this event
      adequately, several goals should be pursued: first, attenuate pain; second,
      favour progression and spontaneous expulsion of stones; third, prevent from
      obstructive and infectious complications. All of the aforementioned points
      pertain to medical management of this disease. Concerning prevention, it is
      widely agreed that pathogenesis of kidney stones is a consequence of
      abnormalities in urine environment, leading to a disequilibrium between promoters
      and inhibitors of crystallization. Therefore, the rationale for therapy is to
      make urine less conductive to stone formation, by both decreasing state of
      saturation and increasing inhibitory potential. In only some types of stone
      forming salts it is possible to obtain undersaturation with the solid phase.
      Indeed, uric acid stones can be chemically dissolved by using alkali and
      allopurinol. To a lesser extent, this also applies to cystine stones, with the
      use of thiols and alkali. In these subsets, the aforementioned tools are also
      effective to prevent new stone formation. Much more challenging appears the
      treatment of calcium containing stones. About 10% of such stones is caused by
      systemic disorders and, in these cases, the prevention of new stones is
      successfully accomplished by curing the underlying disease. For instance,
      parathyroidectomy cures calcium nephrolithiasis in case of hyperparathyroidism.
      However, the majority of patients with calcium stones are idiopathic stone
      formers, in whom metabolic abnormalities often occur, namely, hypercalciuria,
      hyperoxaluria, hypocitraturia. The correction of these abnormalities by using
      thiazide diuretics, alkaline citrates, potassium phosphate and bisphosphonates is
      based on the prevailing metabolic defect. Among the most recent available tools,
      Oxalobacter Formigenes and probiotics have been proposed to treat primary or
      secondary hyperoxalurias. In general, the treatment of stone disease reduces its
      recurrence rate, but only seldom results in stable remission. Anyway, less stones
      mean reduction of the need for urological procedures and the associated infective
      or obstructive complications. Of course, medical prevention implies financial
      efforts, but a careful cost to benefit analysis demonstrates that these are well
      justified.

PMID- 22460997
TI  - Surgical approach to urolithiasis: the state of art.
AB  - Twenty years after its introduction, extracorporeal lithotripsy is still
      predominantly used. The increased prevalence of small urinary calculi has brought
      about a change in clinical symptoms, with frequent episodes of renal-ureteral
      colic, persistent pain and hydronephrosis. In everyday urological practice
      armamentarium there are several methods and techniques to actively remove the
      stones that can obtain good levels of efficacy and good patients compliance. We
      aimed to describe the principal surgical techniques.

PMID- 22460996
TI  - Dietary treatment of nephrolithiasis.
AB  - The prevalence of idiopathic nephrolithiasis is increasing in rich countries.
      Dietary manipulation could contribute to the prevention of both its first
      appearance and the recurrence of the disease. The target of dietary treatment is
      to decrease the "urinary lithogenic risk factors" such as low urine volume,
      hypercalciuria, hyperoxaluria, hyperuricosuria, hyperphosphaturia,
      hypocitraturia, hypomagnesuria and excessively alkaline or acid urinary pH. Due
      to the lack of randomized controlled trials focused on this problem, there is not
      ample evidence to confidently recommend dietary changes. Despite this, numerous
      recent and past experiences support modification of diet as having a primary role
      in the prevention of nephrolithiasis. In particular, it is recommended to limit
      animal protein and salt intake, to consume milk and derivatives in amounts
      corresponding to calcium intake of about 1200 mg/day and to assume fiber (40
      g/day), vegetables and fruit daily avoiding foods with high oxalate content.
      Furthermore, vitamin C intake not exceeding 1500 mg/day plays a protective role
      as well as avoiding vitamin B6 deficiency and abstaining, if possible, from
      vitamin D supplements. Lastly, it is recommended to drink enough water to bring
      the urinary volume up to at least 2 L/day and, as much as possible, to use fresh
      or frozen products rather than prepacked or precooked foods which are often too
      rich in sodium chloride.

PMID- 22460998
TI  - The general practitioner and nephrolithiasis.
AB  - Nephrolithiasis is a multifactorial disease the genesis of which is influenced by
      genetic, metabolic and environmental factors which determine a series of
      alterations in the urinary excretion of a number of substances, the cause of the
      disease itself. The general practitioner is often the first professional to be
      consulted as regards clinical and therapeutic treatment at the moment of the
      onset of nephrolithiasis, renal colic, inasmuch as contacted directly by the
      patient. His role however should not be limited to this initial phase but becomes
      of strategic importance throughout the subsequent diagnostic procedure; this is
      especially true with regard to relapses, in correctly placing the patient and, if
      necessary, referring him/her to the most appropriate specialist area. Running
      through the entire process which the lithiasic patient encounters from the onset
      of the disease until therapeutic treatment begins, it is clear how an appropriate
      initial approach can, in many cases, simplify and optimise such process. On the
      basis therefore of a complete medical record, and a few simple, biochemical and
      instrumental tests, the general practitioner is in a position to decide whether
      to treat the patient directly or to refer him/her to the most appropriate
      specialist field for investigation at a higher level.Over the last decades
      nephrolithiasis has progressively changed from being a disease of mainly surgical
      pertinence to being one of multidisciplinary medical interest in which the figure
      of the General Practitioner has a primary role, both during the initial
      diagnostic phase, by means of the correct physio-pathological identification of
      the problem, and in the subsequent phases as regards the choice and co-ordination
      of the various specialists involved.

PMID- 22461000
TI  - New dosing options in osteoporosis treatment: clinical evidence on Risedronate
      75mg monthly treatment.
AB  - Prevention of osteoporosis fractures is currently possible by implementing
      lifestyle changes as well as with effective treatments. The role played by
      different agents is particularly important in reducing the risk of hip fracture,
      which is certainly the most severe consequence of osteoporosis in terms of
      deteriorating quality of life for the patient, reduced life expectancy and health
      care costs.In order to choose an adequate treatment, therapies with well
      established efficacy should be considered. In addition, for medical treatment
      success, patient adherence is essential. Recently published clinical data show
      that risedronate 75mg, administered monthly on two consecutive days, equivalent
      to risedronate 5 mg daily in terms of BMD changes, bone turnover markers and
      incidence of new vertebral fractures, and has an equivalent safety profile. The
      new risedronate 75mg monthly formulation, administered on two consecutive days,
      is therefore the first and only oral monthly therapy with proven efficacy in
      reducing the risk of vertebral, non-vertebral and hip fractures, and a safety
      profile confirmed by Phase III trials and 8-year post-marketing experience of
      risedronate. Monthly dosing may offer the advantage of improving patient
      compliance and persistence on the treatment, thanks to the less frequent
      administration.

PMID- 22460999
TI  - Genetic tests and genomic biomarkers: regulation, qualification and validation.
AB  - The identification of new risk factors for specific diseases is an enduring theme
      in medical research. Advances in molecular biology, genetics, and computational
      biology are accelerating the pace of this work. The research seeks to increase
      our understanding of the causes of diseases, but there is also hope that the
      recognition of new risk factors will lead to improved methods for identifying
      persons who are in the early stages of, or at high risk for, the diseases of
      concern. Research has shown, however, that a genomic biomarker must have a much
      stronger association with the disease outcome than we ordinarily see in etiologic
      research if it is to provide a basis for early diagnosis or prediction in
      individual patients. However, even if the literature contains ~150,000 reports of
      disease-associated molecular markers, there are still very few validated
      biomarkers of proven and robust clinical utility. At present there is no
      established, standardized means for validating the association between a marker
      (or set of markers) and clinical outcomes. The Regulatory Authorities have
      undertaken a number of initiatives in order to enhance the use of biomarkers in
      drug development, to promote a more informed drug development and maximise the
      benefit of innovative medicines to the patients.

PMID- 22461001
TI  - In vitro study of elution kinetics and bio-activity of meropenem-loaded acrylic
      bone cement.
AB  - BACKGROUND: Use of antibiotic-loaded acrylic bone cement to treat orthopaedic
      infections continues to remain popular, but resistance to routinely used
      antibiotics has led to the search for alternative, more effective antibiotics. We
      studied, in vitro, the elution kinetics and bio-activity of different
      concentrations of meropenem-loaded acrylic bone cement. METHODS: Meropenem-loaded
      bone cement cylinders of different concentrations were serially immersed in
      normal saline. Elution kinetics was studied by measuring the drug concentration
      in the eluate, collected at pre-determined intervals, by high-performance liquid
      chromatography. Bio-activity of the eluate of two different antibiotic
      concentrations was tested for a period of 3 weeks against each of the following
      organisms: Staphylococcus aureus ATCC 2593 (MSSA), Enterococcus faecalis ATCC
      29212, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, S. aureus
      ATCC 43300 (MRSA) and Klebsiella pneumoniae ATCC 700603 (ESBL). RESULTS:
      Meropenem elutes from acrylic bone cement for a period of 3-27 days depending on
      the concentration of antibiotic. Higher doses of antibiotic concentration
      resulted in greater elution of the antibiotic. The eluate was found to be
      biologically active against S. aureus ATCC 2593 (MSSA), P. aeruginosa ATCC 27853,
      E. coli ATCC 25922 and K. pneumoniae ATCC 700603 (ESBL) for a period of 3 weeks.
      CONCLUSIONS: The elution of meropenem is in keeping with typical antibiotic
      loaded acrylic bone cement elution characteristics. The use of high-dose
      meropenem-loaded acrylic bone cement seems to be an attractive option for
      treatment of resistant Gram-negative orthopaedic infections but needs to be
      tested in vivo.

PMID- 22461002
TI  - Development of a stereoselective Ugi reaction starting from an oxanorbornene beta
      amino acid derivative.
AB  - We have synthesised a novel oxanorbornene beta-aminoacid derivative and employed
      it in a stereoselective Ugi reaction. Hypothesis regarding the mechanism taking
      place during the reaction have been made and validated through the determination
      of the relative and absolute configuration of the Ugi adducts. Use of the correct
      choice of solvents can increase stereoselection. The resulting bicyclic
      peptidomimetics can be used as a novel class of pluripotent substrates to be
      elaborated according to the synthetic strategies previously elaborated in our
      laboratories.

PMID- 22461003
TI  - Critical illness-related bone loss is associated with osteoclastic and angiogenic
      abnormalities.
AB  - Critically ill patients are at increased risk of fractures during rehabilitation,
      and can experience impaired healing of traumatic and surgical bone fractures. In
      addition, markers of bone resorption are markedly increased in critically ill
      patients, while markers of bone formation are decreased. In the current study, we
      have directly investigated the effect of critical illness on bone metabolism and
      repair. In a human in vitro model of critical illness, Fluorescence-activated
      cell sorting (FACS) analysis revealed an increase in circulating CD14+/CD11b+
      osteoclast precursors in critically ill patient peripheral blood compared to
      healthy controls. In addition, the formation of osteoclasts was increased in
      patient peripheral blood mononuclear cell (PBMC) cultures compared to healthy
      controls, both in the presence and absence of osteoclastogenic factors receptor
      activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M
      CSF). Culturing PBMCs with 10% critically ill patient serum further increased
      osteoclast formation and activity in patient PBMCs only, and neutralization
      studies revealed that immunoglobulin G (IgG) antibody signaling through the
      immunoreceptor Fc receptor common gamma chain III (FcRgammaIII) played an
      important role. When analyzing bone formation, no differences in osteogenic
      differentiation were observed using human periosteal-derived cells (hPDCs)
      treated with patient serum in vitro, but a decrease in the expression of vascular
      endothelial growth factor receptor 1 (VEGF-R1) suggested impaired
      vascularization. This was confirmed using serum-treated hPDCs implanted onto
      calcium phosphate scaffolds in a murine in vivo model of bone formation, where
      decreased vascularization and increased osteoclast activity led to a decrease in
      bone formation in scaffolds with patient serum-treated hPDCs. Together, these
      findings may help to define novel therapeutic targets to prevent bone loss and
      optimize fracture healing in critically ill patients.

PMID- 22461004
TI  - The effect of GM-CSF on development and aneuploidy in murine blastocysts.
AB  - BACKGROUND: Growth factors and cytokines are present in small quantities in the
      oviduct and uterus and some are synthesized by the growing embryo. Granulocytes
      macrophage colony-stimulating factor (GM-CSF) is known as an important regulator,
      which enhances cell proliferation and reduces apoptosis in developing
      blastocysts, during normal fetal and placental development. The purpose of this
      study is to investigate whether adding GM-CSF to the culture media affects
      blastulation or the chromosomal status of mouse embryos. METHODS: Murine embryos
      were cultured in vitro from the 2-cell stage until the blastocyst stage in the
      presence of different concentrations of GM-CSF of 0 ng/ml (control), 1, 2, 5 and
      10 ng/ml. The development of each embryo was noted and the embryos were then
      spread for fluorescence in situ hybridization (FISH) using locus-specific probes
      (LSI) for chromosomes 2, 11 and 16 in all embryos. RESULTS: No difference in the
      blastulation potential was noted with the addition of 1 and 2 ng/ml of GM-CSF
      compared with the controls, but there was a significant decrease (P < 0.001) in
      the blastulation rate in the 5 and 10 ng/ml concentrations. The rate of
      mosaicism/aneuploidy noted in all GM-CSF groups (1, 2, 5 and 10 ng/ml) was
      slightly higher than in the control group (0 ng/ml GM-CSF) but the differences
      were not significant. In the mosaic embryos from the GM-CSF cultured groups, the
      percentage of aneuploid cells was statistically higher than in the control group.
      CONCLUSIONS: GM-CSF exerted a negative impact on blastocyst development at higher
      concentrations. GM-CSF did not affect the rates of mosaicism/aneuploidy, but did
      increase the percentage of aneuploid cells within the mosaic embryos. Adding GM
      CSF to the culture media for clinical use requires further studies either on
      human or animal models to evaluate its long-term effects.

PMID- 22461005
TI  - Newly evolved genes: moving from comparative genomics to functional studies in
      model systems. How important is genetic novelty for species adaptation and
      diversification?
AB  - Genes are gained and lost over the course of evolution. A recent study found that
      over 1,800 new genes have appeared during primate evolution and that an
      unexpectedly high proportion of these genes are expressed in the human brain. But
      what are the molecular functions of newly evolved genes and what is their impact
      on an organism's fitness? The acquisition of new genes may provide a rich source
      of genetic diversity that fuels evolutionary innovation. Although gene
      manipulation experiments are not feasible in humans, studies in model organisms,
      such as Drosophila melanogaster, have shown that new genes can quickly become
      integrated into genetic networks and become essential for survival or fertility.
      Future studies of new genes, especially chimeric genes, and their functions will
      help determine the role of genetic novelty in the adaptation and diversification
      of species.

PMID- 22461006
TI  - FLOTAC for the diagnosis of Hymenolepis spp. infection: proof-of-concept and
      comparing diagnostic accuracy with other methods.
AB  - Hymenolepis nana is the most common cestode parasitizing humans, yet it is under
      diagnosed. We determined the optimal flotation solution (FS) for the diagnosis of
      this intestinal parasite with the FLOTAC method, and compared its diagnostic
      accuracy with an ether-concentration technique and the Kato-Katz method. Zinc
      sulphate (specific gravity 1.20) proved to be the best-performing FS. Using this
      FS, we detected 65 H. nana infections among 234 fixed fecal samples from Tajik
      and Sahrawi children (prevalence 27.8 %). The ether-concentration technique
      detected 40 infections (prevalence 17.1 %) in the same samples. Considering the
      combined results as a reference, the sensitivities of FLOTAC and ether
      concentration were 95.6 % and 58.8 %, respectively. The Kato-Katz method resulted
      in a prevalence of only 8.7 %. In terms of eggs per gram of stool, a
      significantly (P <0.05) higher value was obtained with the FLOTAC and Kato-Katz
      techniques compared to ether-concentration. In another study carried out in
      China, the FLOTAC method detected six Hymenolepis diminuta infections in 302
      fecal samples, whereas five samples were found positive with the Kato-Katz
      technique. We conclude that FLOTAC is an accurate coprodiagnostic technique for
      H. nana and H. diminuta, two species which join a growing list of intestinal
      parasites that can be reliably diagnosed by this technique.

PMID- 22461007
TI  - Morphological and molecular identification of Hysterothylacium longilabrum sp.
      nov. (Nematoda: Anisakidae) and larvae of different stages from marine fishes in
      the South China Sea.
AB  - A new ascaridoid nematode Hysterothylacium longilabrum sp. nov. collected from
      the intestine and stomach of the marine fishes Siganus fuscescens (Houttuyn) and
      Siganus canaliculatus (Park) (Perciformes: Siganidae) in the South China Sea is
      described and illustrated. The new species differs from its congeners by the
      unusually long lips, the very short intestinal caecum and relatively long
      ventricular appendix (ratio of intestinal caecum to ventricular appendix, 1:2.38
      5.50), the long spicules (1.96-3.28 mm long, representing 7.42-11.4% of the body
      length), the number and arrangement of male caudal papillae [38-43 pairs in
      total, arranged as: 31-34 pairs precloacal, 1 pair of paracloacal and 4-6 pairs
      postcloacal (the second or fourth pair double)] and the presence of a particular
      medioventral precloacal papilla in the male. Molecular analyses by sequencing and
      comparing the internal transcribed spacer (ITS) of the ribosomal DNA of H.
      longilabrum sp. nov. with the closely related nematode sequences seem to support
      the validity of the new species based on the morphological observation. In
      addition, the third- and fourth-stage larvae of the new species are also exactly
      identified and described by analysing and comparing the ITS sequence with the
      adult, and the result is a substantial step toward elucidating its life cycle.

PMID- 22461008
TI  - Galalpha1-4Galbeta1-3GalNAc is the dominant epitope of Em2 antigen, the mucin
      type glycoprotein from Echinococcus multilocularis.
AB  - The larval stage of Echinococcus multilocularis causes alveolar echinococcosis in
      human. In serodiagnosis of alveolar echinococcosis, specific reactions have been
      noted not only against protein antigens but also carbohydrates. With regard to
      protein antigens, the recent development of recombinant antigens has contributed
      to an improvement in serodiagnostic examination. On the contrary, the preparation
      of carbohydrate antigen still depends on extraction from crude antigens, and
      isolation is usually accompanied with difficulty; consequently, it is rare to
      examine individual antigenicity of carbohydrates. However, parasitic helminths
      express various antigenic carbohydrates. In the case of Echinococcus granulosus,
      antigenic glycoproteins of the laminated layer have been reported. Furthermore,
      the laminated layer of E. multilocularis contains Em2 antigen which is a famous
      mucin-type glycoprotein and which seems to play an important role in metacestode
      survival mechanisms within the immunologically reacting host; nevertheless, the
      anomeric configurations and the individual antigenicity of Em2 O-glycans have not
      been confirmed so far. Under these circumstances, we introduced a chemical
      synthesis to get pure oligosaccharides in order to assess diagnostic performance.
      In our previous study, 11 oligosaccharides have already been prepared by
      stereocontrolled syntheses. Among them, three synthetic oligosaccharides showed
      antigenicity. Our aim is to investigate correct sequence and serodiagnostic
      potential of the dominant epitope of Em2. This study provided important
      diagnostic information: (1) the trisaccharide Galalpha1-4Galbeta1-3GalNAc
      sequence is the dominant epitope of Em2 (sensitivity 95.0 %), (2) Trematoda
      expresses carbohydrates with the similar trisaccharide sequence, and (3) the
      terminal Galalpha1-4Gal sequence is a candidate for the widely common epitope
      that accounts for the cross-reaction.

PMID- 22461009
TI  - Diosgenin promotes oligodendrocyte progenitor cell differentiation through
      estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.
AB  - Differentiation of oligodendrocyte progenitor cells (OPCs) into mature
      oligodendrocytes is a prerequisite for remyelination after demyelination, and
      impairment of this process is suggested to be a major reason for remyelination
      failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic
      use in many diseases, but little is known about its effect on the central nervous
      system. In this study, using a purified rat OPC culture model, we show that
      diosgenin significantly and specifically promotes OPC differentiation without
      affecting the viability, proliferation, or migration of OPC. Interestingly, the
      effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI
      182780 but not by glucocorticoid and progesterone receptor antagonist RU38486,
      nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is
      revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can
      activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER.
      The pro-differentiation effect of diosgenin can also be obstructed by the ERK
      inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it
      is demonstrated that diosgenin administration significantly accelerates/enhances
      remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and
      real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes
      in the corpus callosum while it does not affect the number of OPCs. Taking
      together, our results suggest that diosgenin promotes the differentiation of OPC
      into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to
      accelerate remyelination, which implicates a novel therapeutic usage of this
      steroidal natural product in demyelinating diseases such as multiple sclerosis
      (MS).

PMID- 22461010
TI  - When suffering begets suffering: the psychology of competitive victimhood between
      adversarial groups in violent conflicts.
AB  - Inter-group competitive victimhood (CV) describes the efforts of members of
      groups involved in violent conflicts to establish that their group has suffered
      more than their adversarial group. Such efforts contribute to conflicts'
      escalation and impede their peaceful resolution. CV stems from groups' general
      tendency to compete with each other, along with the deep sense of victimization
      resulting from conflicts. The authors point to biases that contribute to groups'
      engagement in CV, describe five dimensions of victimhood over which groups may
      compete, and contend that such competition serves various functions that
      contribute to the maintenance of conflicts. Drawing on the Needs-Based Model,
      they suggest that CV may reflect groups' motivations to restore power or moral
      acceptance. They then review evidence of the negative consequences of CV for
      inter-group forgiveness and suggest potential strategies to reduce CV. Finally,
      the authors discuss potential moderators and directions for future research.

PMID- 22461011
TI  - Complete conformational space of the potential HIV-1 reverse transcriptase
      inhibitors d4U and d4C. A quantum chemical study.
AB  - A comprehensive quantum-chemical conformational analysis of two nucleoside
      analogues, 2',3'-didehydro-2',3'-dideoxyuridine (d4U) and 2',3'-didehydro-2',3'
      dideoxycytidine (d4C), is reported. The electronic structure calculations were
      performed at the MP2/6-311++G(d,p)//B3LYP/6-31++G(d,p) level of theory. It was
      found that d4U and d4C adopt 20 conformers and 19 conformers, respectively, which
      correspond to local minima on the respective potential energy landscapes. QTAIM
      and NBO analyses show that the d4U and d4C conformers are stabilised by a
      complicated network of specific intramolecular interactions, which includes
      conventional (OHO) and non-conventional (CHO, CHHC) H-bonds as well as closed
      shell van der Waals (CO) contacts. A satisfactory linear correlation was found
      between Grunenberg's compliance constants for closed-shell intramolecular
      interactions and their energy. It is shown that there are no conformational
      obstacles for incorporation of d4U and d4C into the double helical A and B forms
      of DNA. The less pronounced biological activity of d4U as compared to 2',3'
      didehydro-2',3'-dideoxythymidine (d4T) is most likely due to the presence of the
      bulky methyl group at the 5-position of d4T, which can be recognised by target
      enzymes. 

PMID- 22461012
TI  - Risk of malignancy associated with Lyme disease: still up in the air.

PMID- 22461013
TI  - What is the current practice in Europe when difficult shoulder injuries are
      treated?

PMID- 22461014
TI  - Scapular dyskinesis and SICK scapula syndrome following surgical treatment of
      type III acute acromioclavicular dislocations.
AB  - PURPOSE: To evaluate the incidence of scapular dyskinesis and SICK scapula
      syndrome (defined as scapular malposition, infero-medial border prominence,
      coracoid pain and malposition, and dyskinesis of scapular movement) in patients
      treated surgically for acute type III AC dislocation. METHODS: Development of
      scapular dyskinesis and SICK scapula syndrome following conservative treatment
      has been described in the literature. In the present study, we evaluated 34
      patients treated with different surgical techniques for acute type III AC
      dislocations. Functional outcome, radiographic evaluation of clavicular reduction
      and scapular kinematics were all evaluated. RESULTS: Scapular dyskinesis was
      observed in only 4 (11.7%) patients, of which only 1 (2.9% of the sample) was
      affected by SICK scapula syndrome. Scapular dyskinesis was classified as type I
      in 3 cases (75%) and type III in 1 case (25%). Constant shoulder scores (mean
      95.7 points, SD +/- 5.3) and Simple Shoulder Test results (mean 11.2 points, SD
      +/- 0.8) were excellent. Recurrence of separation was observed in 4 patients.
      CONCLUSIONS: Surgical treatment of type III acute AC joint dislocations is
      associated with a lower incidence of scapular dyskinesis and SICK scapula
      syndrome, if compared to data reported in the literature on conservative
      treatment. LEVEL OF EVIDENCE: Retrospective study, Level IV.

PMID- 22460971
TI  - Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive
      patients in high-income countries.
AB  - BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency
      virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART)
      is difficult to interpret causally. Furthermore, the role of unmasking immune
      reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the
      effect of cART on tuberculosis incidence in HIV-positive individuals in high
      income countries. METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts
      from the United States and Europe of HIV-positive, ART-naive, AIDS-free
      individuals aged >=18 years with baseline CD4 cell count and HIV RNA levels
      followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART
      versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via
      inverse probability weighting. RESULTS: Of 65 121 individuals, 712 developed
      tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000
      person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95%
      confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for
      individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4
      cell count of <50 cells/MUL. Compared with people who had not started cART, HRs
      differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation
      <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation >=3 months ago.
      Compared with people who had not initiated cART, HRs <3 months after cART
      initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95%
      CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30
      (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/MUL.
      CONCLUSIONS: Tuberculosis incidence decreased after cART initiation but not among
      people >50 years old or with CD4 cell counts of <50 cells/MUL. Despite an overall
      decrease in tuberculosis incidence, the increased rate during 3 months of ART
      suggests unmasking IRIS.

PMID- 22461015
TI  - Effect of graft tensioning on mechanical restoration in a rat model of anterior
      cruciate ligament reconstruction using free tendon graft.
AB  - PURPOSE: Initial graft tensioning is important in anterior cruciate ligament
      reconstruction (ACLR), but its effect on graft healing is still not clear. Since
      all previous animal studies on graft tensioning used bone-patellar tendon-bone,
      this study aimed to investigate the effect of initial graft tensioning on ACLR
      using tendon graft. METHODS: Fifty-five Sprague-Dawley rats underwent ACLR using
      flexor digitorum longus tendon graft. A constant force of 2 or 4 N was applied
      during graft fixation. At 0, 2, and 6 weeks, knee samples were harvested (n = 6)
      for static knee laxity test and graft pull-out test. Histological examination was
      performed at 2 and 6 weeks post-injury (n = 4). RESULTS: At time zero, knee
      laxity was restored by ACLR with 2 or 4 N tensioning as compared to ACL-deficient
      group (p < 0.001), and the 4 N group exhibited a better restoration as compared
      to 2 N group (p = 0.031). At week 2 post-operation, the 4 N group still exhibited
      a better restoration in knee laxity (p = 0.001) and knee stiffness (p = 0.002)
      than the 2 N group; the graft pull-out force (p = 0.032) and stiffness (p =
      0.010) were also higher. At week 6 post-operation, there was no significant
      difference between the 2 and 4 N group in knee laxity and graft pull-out
      strength. Histological examination showed that the beneficial effect of higher
      initial graft tension may be contributed by maintenance of graft integrity at mid
      substance and reduction in adverse peri-graft bone changes in the femoral tunnel
      region. CONCLUSIONS: A higher initial graft tension favours the restoration of
      knee laxity and promotes graft healing in ACLR using free tendon graft in the rat
      model.

PMID- 22461018
TI  - Quality of polyp resection during colonoscopy: are we achieving polyp clearance?
AB  - BACKGROUND AND STUDY AIM: Currently colonoscopy quality indicators emphasize our
      ability to improve polyp detection (e.g., preparation quality, withdrawal times
      of >=6 min). The completeness of a polyp resection may also be an important
      determinant of quality and efficient colonoscopy. The primary aim of this study
      was to determine the incidence of an incomplete polyp resection despite a
      perceived complete polypectomy. PATIENTS AND METHODS: This was a retrospective
      quality assurance project conducted at the San Diego Veterans Affair Medical
      Center and University of California San Diego Medical Center from July 2007 to
      April 2008. The patients recruited to this study were undergoing surveillance and
      screening colonoscopy. The resection quality was evaluated in 65 polyps of 47
      patients. Twenty-two polyps were removed with standard biopsy forceps, jumbo
      forceps (18), hot snare (18), and cold snare (7). Biopsies were taken from the
      post-polypectomy site base and perimeter for histologic examination in order to
      confirm histologic absence of all polypoid appearing mucosa. RESULTS: The post
      polypectomy sites of ten polyps (15%) were found to have residual polypoid
      tissue. Six were removed by standard biopsy forceps, jumbo forceps (2), hot snare
      (1), and cold snare (1). When compared to other polypectomy devices, standard
      biopsy forceps were more likely to result in an incomplete resection (27 vs. 9%;
      P = 0.076). CONCLUSIONS: The endoscopist may not be visually accurate in
      determining when a polyp is completely resected, and alternative devices and
      techniques for polyp resection should be considered.

PMID- 22461017
TI  - Clinical features and prognosis of discoid medial meniscus.
AB  - PURPOSE: To evaluate the clinical manifestations and the outcome of surgical
      treatment of discoid medial meniscus. METHODS: Records of 13 patients with
      discoid medial meniscus were retrospectively reviewed for their epidemiology,
      clinical manifestations, operation methods, treatment outcome and radiographic
      characteristics. RESULTS: The 13 cases of discoid medial meniscal injury took up
      1.5 0/00 of the overall meniscal injuries treated at our institute during the 44
      year period. Patients presented with knee pain (13 patients), giving away (10
      patients), swelling (9 patients) and snapping (9 patients). The most common
      physical signs were medial joint line tenderness (13 patients) and positive
      McMurray test (11 patients). Ten patients required total meniscectomy. There were
      excellent short-term results: the median Tegner score was 7, and the mean Lysholm
      score was 94.8 +/- 2.4 at two-year follow-up. However, the long-term outcome was
      not as good with degenerative changes in the medial compartment of all the
      involved knees. CONCLUSION: The discoid medial meniscus is extremely rare. The
      clinical signs and symptoms of discoid medial meniscal injuries are similar to
      those of any other meniscal injury. No Wrisberg-ligament type abnormality was
      found. Meniscectomy for discoid medial meniscus produced promising short-term
      results and deteriorating long-term results with secondary degeneration of
      cartilage in the medial compartment. LEVEL OF EVIDENCE: Retrospective case
      series, Level IV.

PMID- 22461016
TI  - Close-looped graft suturing improves mechanical properties of interference screw
      fixation in ACL reconstruction.
AB  - PURPOSE: In anterior cruciate ligament reconstruction with looped soft-tissue
      grafts, an interference screw is frequently used for tibial fixation. This study
      compared three alternatives thought to improve the initial mechanical properties
      of direct bioabsorbable interference screw fixation: suturing the graft to close
      the loop, adding a supplementary staple, or increasing the oversize of the screw
      diameter relative to the bone tunnel from 1 to 2 mm. METHODS: Twenty-eight
      porcine tibiae and porcine flexor digitorum profundus tendons were randomized
      into four testing groups: a base fixation using 10-mm-diameter screw with open
      looped graft, base fixation supplemented by an extracortical staple, base
      fixation but closing the looped graft by suturing its ends, and base fixation but
      using an 11-mm screw. Graft and bone tunnel diameters were 9 mm in all specimens.
      Constructs were subjected to cyclic tensile load and finally pulled to failure to
      determine their structural properties. RESULTS: The main mode of failure in all
      groups was pull-out of tendon strands after slippage past the screw. The sutured
      graft group displayed significantly lower residual displacement (mean value
      reduction: 47-67 %) and higher yield load (mean value increase: 38-54 %) than any
      alternative tested. No other statistical differences were found. CONCLUSIONS:
      Suturing a soft-tissue graft to form a closed loop enhanced the initial
      mechanical properties of tibial fixation with a bioabsorbable interference screw
      in anterior cruciate ligament reconstructions using a porcine model, and thus,
      this may be an efficient means to help in reducing post-operative laxity and
      early clinical failure. No mechanical improvement was observed for an open-looped
      tendon graft by adding an extracortical staple to supplement the screw fixation
      or by increasing the oversize of the screw to tunnel diameter from 1 to 2 mm.

PMID- 22461019
TI  - Human deficiencies of fucosylation and sialylation affecting selectin ligands.
AB  - Selectins are carbohydrate-binding adhesion molecules that are required for
      leukocyte trafficking to secondary lymphoid organs and to sites of infection.
      They interact with fucosylated and sialylated ligands bearing sialyl-Lewis X as a
      minimal carbohydrate structure. With this in mind, it should be expected that
      individuals with deficient fucosylation or sialylation show immunodeficiency.
      However, as this review shows, the picture appears to be more complex and more
      interesting. Although there are only few patients with such glycosylation
      defects, they have turned out to be very instructive for our understanding of the
      functions of fucosylation and sialylation in immunity, development and
      hemostasis.

PMID- 22461021
TI  - The nature of [PdCl(2)(C(2)H(4))(H(2)O)] as an active species in the Wacker
      process: new insights from ab initio molecular dynamics simulations.
AB  - First-principles molecular dynamics coupled with metadynamics have been used to
      gain a deeper insight into the reaction mechanism of the Wacker process by
      determining the nature of the active species. An explicit and dynamic
      representation of the aqueous solvent, which was essential for modeling this
      reaction, was efficiently included into the simulations. Prompted by our earlier
      results, which showed that the configuration of the catalytically active species
      [PdCl(2)(H(2)O)(C(2)H(4))] was crucial in the subsequent steps of the Wacker
      process, herein we focused on the preceding equilibria that led to the formation
      of both the cis and trans isomers. Starting from the initial catalyst,
      [PdCl(4)](2-), the free-energy barriers for the forward and backward reactions
      were calculated. These results confirmed the relevance of the trans intermediate
      in the reaction mechanism, whilst conversely, they showed that the cis
      configuration played no role in it. This sole participation of the trans
      intermediate has some very important implications; besides the mechanistic
      interpretation of the initial steps in the Wacker reaction mechanism, the
      analysis of these equilibria provides additional information about the chemical
      nature of these ligand-substitution processes.

PMID- 22461020
TI  - Roles for major histocompatibility complex glycosylation in immune function.
AB  - The major histocompatibility complex (MHC) glycoprotein family, also referred to
      as human leukocyte antigens, present endogenous and exogenous antigens to T
      lymphocytes for recognition and response. These molecules play a central role in
      enabling the immune system to distinguish self from non-self, which is the basis
      for protective immunity against pathogenic infections and disease while at the
      same time representing a serious obstacle for tissue transplantation. All known
      MHC family members, like the majority of secreted, cell surface, and other immune
      related molecules, carry asparagine (N)-linked glycans. The immune system has
      evolved increasing complexity in higher-order organisms along with a more complex
      pattern of protein glycosylation, a relationship that may contribute to immune
      function beyond the early protein quality control events in the endoplasmic
      reticulum that are commonly known. The broad MHC family maintains peptide
      sequence motifs for glycosylation at sites that are highly conserved across
      evolution, suggesting importance, yet functional roles for these glycans remain
      largely elusive. In this review, we will summarize what is known about MHC
      glycosylation and provide new insight for additional functional roles for this
      glycoprotein modification in mediating immune responses.

PMID- 22461022
TI  - Loss of responsiveness of circular smooth muscle cells from the guinea pig ileum
      is associated with changes in gap junction coupling.
AB  - Gap junction coupling and neuromuscular transmission to smooth muscle were
      studied in the first 4 h after preparations were set up in vitro. Intracellular
      recordings were made from smooth muscle cells of guinea pig ileum. Fast
      inhibitory junction potentials (IJPs) were small (1.3 +/- 1.0 mV) in the first 30
      min but increased significantly over the first 120 min to 15.8 +/- 0.9 mV (n =
      12, P < 0.001). Comparable increases in slow IJPs and excitatory junction
      potentials were also observed. During the same period, resting membrane potential
      depolarized from -58.8 +/- 1.4 to -47.2 +/- 0.4 mV (n = 12, P < 0.001). Input
      resistance, estimated by intracellular current injection, decreased in parallel
      (P < 0.05), and dye coupling, measured by intracellular injection of
      carboxyfluorescein, increased (P < 0.001). Input resistance was higher and dye
      coupling was less in longitudinal than circular smooth muscle cells. Gap junction
      blockers [carbenoxolone (100 MUM), 18beta-glycyrrhetinic acid (10 MUM), and 2
      aminoethoxydiphenyl borate (50 MUM)] hyperpolarized coupled circular smooth
      muscle cells, reduced the amplitude of fast and slow IJPs and excitatory junction
      potentials, increased input resistance, and reduced dye coupling. Local
      application of ATP (10 mM) mimicked IJPs and showed comparable increases in
      amplitude over the first 120 min; carbenoxolone and 2-aminoethoxydiphenyl borate
      significantly reduced ATP-evoked hyperpolarizations in coupled cells. In
      contrast, synaptic transmission between myenteric neurons was not suppressed
      during the first 30 min. Gap junction coupling between circular smooth muscle
      cells in isolated preparations was initially disrupted but recovered over the
      next 120 min to a steady level. This was associated with potent effects on
      neuromuscular transmission and responses to exogenous ATP.

PMID- 22461023
TI  - Effect of peripheral administration of cholecystokinin on food intake in
      apolipoprotein AIV knockout mice.
AB  - Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors
      secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has
      an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In
      this study, we determined whether CCK-8 (1, 3, or 5 MUg/kg ip) reduces food
      intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type
      (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice
      had significantly reduced 30-min food intake following all doses of CCK-8,
      whereas WT mice had reduced food intake only at doses of 3 MUg/kg and above. Post
      hoc analysis revealed that the reduction of 10-min and 30-min food intake
      elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice
      than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in
      the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that
      in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was
      upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression
      was found in the brain stem of apo AIV KO mice by in situ hybridization. Although
      it is possible that the increased satiating potency of CCK in apo AIV KO mice is
      mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus
      solitarius, additional experiments are required to confirm such a mechanism.

PMID- 22461025
TI  - Altered temporal characteristics of the rectoanal inhibitory reflex in patients
      with abdominal distension.
AB  - The rectoanal inhibitory reflex (RAIR) is important in gas and stool evacuation.
      We examined RAIR features in patients with chronic constipation who exhibited
      bloating with and without abdominal distension, to determine whether alterations
      in RAIR may be a factor in the pathogenesis of abdominal distension. Seventy-five
      female patients with chronic constipation with or without abdominal distension
      were included in the study. The presence or absence of abdominal distension was
      assessed according to the Rome II questionnaire. All patients underwent both RAIR
      and rectal sensitivity testing, and specific RAIR parameters were analyzed.
      Patients were divided into two groups: abdominal bloating with distension (D, n =
      55) and abdominal bloating without distension (ND, n = 20). D had a longer time
      to the onset of anal sphincter inhibition (latency of inhibition) (P = 0.03)
      compared with ND. In logistic regression analysis, a combination of age, latency
      of inhibition and the time measured from onset of inhibition to the point of
      maximum inhibition predicted abdominal distension (P = 0.002). There were no
      differences between groups for the time from point of maximum inhibition to
      recovery and for the percentage of internal anal sphincter relaxation. This is
      the first study to examine the role of RAIR in patients with abdominal
      distension. Female patients with constipation and abdominal distension exhibited
      differences in the temporal characteristics of, but not in the degree of, anal
      sphincter relaxation compared with patients without distension. Since this study
      was uncontrolled, further studies are necessary to determine the contribution of
      altered anorectal reflexes to abdominal distension.

PMID- 22461024
TI  - Knockout of Mkp-1 exacerbates colitis in Il-10-deficient mice.
AB  - Il-10-deficient mice develop colitis associated with exaggerated Th1/Th17
      responses and are a valuable model of inflammatory bowel disease. Mkp-1 is a
      major negative regulator of MAPKs, and its expression is enhanced by IL-10. To
      understand the role of Mkp-1 in the regulation of intestinal mucosal immune
      responses, we studied the effect of Mkp-1 deletion on the pathogenesis of colitis
      in Il-10(-/-) mice. We found that knockout of Mkp-1 on an Il-10(-/-) background
      accelerated the development of colitis. Compared with Il-10(-/-) mice, colitis
      not only appeared earlier but also was more severe in Il-10(-/-)/Mkp-1(-/-) mice.
      Il-10(-/-) mice exhibited a mild intestinal inflammation in the specific pathogen
      free environment, and rectal prolapse rarely appeared before 6 mo of age. In
      contrast, the majority of Il-10(-/-)/Mkp-1(-/-) mice developed severe colitis
      rapidly and presented with rectal prolapse after only 2-3 mo. The colon of Il-10(
      /-)/Mkp-1(-/-) mice showed diffuse transmural chronic inflammation and mucosal
      hyperplasia, with significantly more proliferating crypt epithelial cells than
      those of Il-10(-/-) mice. In addition to the severe colitis, Il-10(-/-)/Mkp-1(-/
      ) mice also developed conjunctivitis and blepharitis. The colon of Il-10(-/-)/Mkp
      1(-/-) mice contained significantly higher levels of proinflammatory cytokines
      and exhibited greater MAPK activities than did the colon of Il-10(-/-) mice.
      Splenocytes and lymphocytes from Il-10(-/-)/Mkp-1(-/-) mice produced higher
      levels of Th1 cytokines ex vivo upon activation than did cells from Il-10(-/-)
      mice. Our studies support a pivotal role of Mkp-1 as a negative regulator of
      mucosal immune responses and highlight its protective function against
      inflammatory bowel disease.

PMID- 22461026
TI  - The transcription factor HNF-4alpha: a key factor of the intestinal uptake of
      fatty acids in mouse.
AB  - With an excessive postprandial accumulation of intestine-derived, triglyceride
      rich lipoproteins being a risk factor of cardiovascular diseases, it is essential
      to characterize the mechanisms controlling the intestinal absorption of dietary
      lipids. Our aim was to investigate the role of the transcription factor
      hepatocyte nuclear factor (HNF)-4alpha in this process. We used transgenic mice
      with a specific and inducible intestinal knockout of Hnf-4alpha gene. One hour
      after a lipid bolus, in the presence of the lipase inhibitor tyloxapol, lower
      amounts of triglycerides were found in both plasma and intestinal epithelium of
      the intestine-specific Hnf-4alpha knockout (Hnf-4alpha(intDelta)) mice compared
      with the Hnf-4alpha(loxP/loxP) control mice. These discrepancies were due to a
      net decrease of the intestinal uptake of fatty acid in Hnf-4alpha(intDelta) mice
      compared with Hnf-4alpha(loxP/loxP) mice, as assessed by the amount of
      radioactivity that was recovered in intestine and plasma after gavage with
      labeled triolein or oleic acid, or in intestinal epithelial cells isolated from
      jejunum after a supply of labeled oleic acid-containing micelles. This decreased
      fatty acid uptake was associated with significant lower levels of the fatty acid
      transport protein-4 mRNA and protein along the intestinal tract and with a lower
      acyl-CoA synthetase activity in Hnf-4alpha(intDelta) mice compared with the
      control mice. We conclude that the transcription factor HNF-4alpha is a key
      factor of the intestinal absorption of dietary lipids, which controls this
      process as early as in the initial step of fatty acid uptake by enterocytes.

PMID- 22461028
TI  - PDGF-alpha stimulates intestinal epithelial cell turnover after massive small
      bowel resection in a rat.
AB  - Numerous cytokines have been shown to affect epithelial cell differentiation and
      proliferation through epithelial-mesenchymal interaction. Growing evidence
      suggests that platelet-derived growth factor (PDGF) signaling is an important
      mediator of these interactions. The purpose of this study was to evaluate the
      effect of PDGF-alpha on enterocyte turnover in a rat model of short bowel
      syndrome (SBS). Male rats were divided into four groups: Sham rats underwent
      bowel transection, Sham-PDGF-alpha rats underwent bowel transection and were
      treated with PDGF-alpha, SBS rats underwent a 75% bowel resection, and SBS-PDGF
      alpha rats underwent bowel resection and were treated with PDGF-alpha. Parameters
      of intestinal adaptation, enterocyte proliferation and apoptosis were determined
      at euthanasia. Illumina's Digital Gene Expression analysis was used to determine
      PDGF-related gene expression profiling. PDGF-alpha and PDGF-alpha receptor (PDGFR
      alpha) expression was determined by real-time PCR. Western blotting was used to
      determine p-ERK, Akt1/2/3, bax, and bcl-2 protein levels. SBS rats demonstrated a
      significant increase in PDGF-alpha and PDGFR-alpha expression in jejunum and
      ileum compared with sham animals. SBS-PDGF-alpha rats demonstrated a significant
      increase in bowel and mucosal weight, villus height, and crypt depth in jejunum
      and ileum compared with SBS animals. PDGF-alpha receptor expression in crypts
      increased in SBS rats (vs. sham) and was accompanied by an increased cell
      proliferation following PDGF-alpha administration. A significant decrease in cell
      apoptosis in this group was correlated with lower bax protein levels. In
      conclusion, in a rat model of SBS, PDGF-alpha stimulates enterocyte turnover,
      which is correlated with upregulated PDGF-alpha receptor expression in the
      remaining small intestine.

PMID- 22461027
TI  - Activation of rat intestinal mucosal mast cells by fat absorption.
AB  - Previous studies have linked certain types of gut mucosal immune cells with fat
      intake. We determined whether fat absorption activates intestinal mucosal mast
      cells (MMC), a key component of the gut mucosal immune system. Conscious
      intestinal lymph fistula rats were used. The mesenteric lymph ducts were
      cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of
      Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine,
      rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC
      degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal
      MMC degranulation was visualized by immunofluorescent microscopy of jejunum
      sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of
      Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in
      lymphatic histamine and PGD(2), ~20-fold increase in lymphatic RMCPII, but only
      onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII
      into lymph increased dose dependently with the amount of lipid fed. In addition,
      i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major
      composite in Liposyn II) significantly increased the lymphatic RMCPII
      concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not
      alter lymph RMCPII secretion. Immunohistochemistry image revealed the
      degranulation of MMC into lamina propria after lipid feeding. These novel
      findings indicate that intestinal MMC are activated and degranulate to release
      MMC mediators to the circulation during fat absorption. This action of fatty acid
      is dose and chain length dependent.

PMID- 22461029
TI  - c-Jun/AP-1 is required for CCK-induced pancreatic acinar cell dedifferentiation
      and DNA synthesis in vitro.
AB  - Endogenous CCK plays an important role in pancreatic regeneration after
      pancreatitis. We used primary culture of mouse pancreatic acinar cells to
      evaluate the effect of CCK on acinar cell morphology and gene expression and to
      determine signaling pathways required for proliferation of acinar cells in vitro.
      Over 4 days in culture, cells grew out from acini and formed patches of
      monolayer, which displayed a reduced expression of acinar cell markers including
      digestive enzymes and Mist1 and an increased expression of ductal and embryonic
      markers, including cytokeratin 7, beta-catenin, E-cadherin, pdx-1, and nestin.
      There was no appearance of stellate cell markers. CCK enhanced cellular
      spreading, DNA synthesis, and cyclin D1 expression. When signaling pathways were
      evaluated, CCK stimulation increased c-Jun expression, JNK and ERK activity, and
      AP-1 activation. Chemical inhibitors of JNK and ERK pathways, dominant-negative
      JNK and c-Jun, and c-Jun shRNA significantly inhibited CCK-induced DNA synthesis,
      CCK-induced AP-1 activation, and cyclin D1 expression. Furthermore, dominant
      negative c-Jun reduced the increased expression of beta-catenin and the decreased
      expression of amylase during culture. These results show that MAPK/c-Jun/AP-1
      pathway plays an important role in pancreatic acinar cell dedifferentiation and
      proliferation in culture. Monolayer culture can serve as a model to study acinar
      cell proliferation similar to regeneration after pancreatitis in vivo.

PMID- 22461030
TI  - A nomenclature for intestinal in vitro cultures.
AB  - Many advances have been reported in the long-term culture of intestinal mucosal
      cells in recent years. A significant number of publications have described new
      culture media, cell formations, and growth patterns. Furthermore, it is now
      possible to study, e.g., the capabilities of isolated stem cells or the
      interactions between stem cells and mesenchyme. However, at the moment there is
      significant variation in the way these structures are described and named. A
      standardized nomenclature would benefit the ability to communicate and compare
      findings from different laboratories using the different culture systems. To
      address this issue, members of the NIH Intestinal Stem Cell Consortium herein
      propose a systematic nomenclature for in vitro cultures of the small and large
      intestine. We begin by describing the structures that are generated by
      preparative steps. We then define and describe structures produced in vitro,
      specifically: enterosphere, enteroid, reconstituted intestinal organoid, induced
      intestinal organoid, colonosphere, colonoid, and colonic organoid.

PMID- 22461031
TI  - Efficient synthesis of pseudopeptidic molecular cages.
AB  - Pseudopeptidic cages have been efficiently prepared by combining a dynamic
      covalent procedure with the suitable preorganization of the building blocks by a
      conformational bias or an anion templation.

PMID- 22461032
TI  - Patterns and prognostic indicators of response to CML treatment in a multi
      country medical record review study.
AB  - We conducted a review of patient medical records to assess treatment response
      patterns and prognostic indicators of response among chronic myeloid leukemia
      (CML) patients in the United States, the United Kingdom, Germany, and Japan. All
      1,063 patients selected met the following inclusion criteria: aged 18 or older
      and in chronic phase at the time of diagnosis, Philadelphia chromosome and/or BCR
      ABL positive, received first-line treatment with imatinib, and not enrolled in a
      randomized clinical trial during the period of retrospective review.
      Multivariable logistic regression models were used to evaluate prognostic
      indicators of complete hematological response (CHR), complete cytogenetic
      response (CCyR), and complete or major molecular response (C/MMR). Among patients
      treated with first-line imatinib, CHR at three months, CCyR at 12 months, and
      C/MMR at 18 months were observed in 53, 53.1, and 57.8 % of patients,
      respectively. Among patients treated with second-line dasatinib or nilotinib, CHR
      was achieved at three months in 49 and 42 %, CCyR at 12 months in 32 and 23 %,
      and MMR at 18 months in 30.5 and 26.1 % of patients, respectively. Prognostic
      indicators of first-line response included age, race, and Sokal score. For second
      line treatment, duration of first-line hematological response and choice of drug
      used were also significant.

PMID- 22461033
TI  - Central nervous system lesions due to juvenile myelomonocytic leukemia progressed
      in a boy undergoing first line chemotherapy.
AB  - Juvenile myelomonocytic leukemia is a rare malignancy that occurs in pediatric
      patients. Previous reports, have described leukemic cells may infiltrate many
      organs, such as the lungs, skin, liver, spleen, and intestines, but not the
      central nervous system, although central nervous system infiltration remains a
      point of concern in every patient with acute leukemia. Here, we present one case
      of a boy with juvenile myelomonocytic leukemia who developed multiple lesions in
      the brain while undergoing chemotherapy with 6-mercaptopurine and cytarabine. We
      diagnosed the central nervous system involvement by magnetic resonance imaging,
      cerebrospinal fluid cytology, and the patient's clinical course. He was treated
      with a high dose of cytarabine and intrathecal chemotherapy, then with unrelated
      cord blood stem cell transplantation. He has been in a first complete remission
      for more than 18 months after cord blood stem cell transplantation without any
      neurological sequelae. In conclusion, we encountered a boy with juvenile
      myelomonocytic leukemia who developed central nervous system lesions under
      standard chemotherapy. We subsequently switched treatment to central nervous
      system-oriented chemotherapy, which resulted in a good clinical condition and
      successful cord blood stem cell transplantation.

PMID- 22461034
TI  - Drug interaction between voriconazole and tacrolimus and its association with the
      bioavailability of oral voriconazole in recipients of allogeneic hematopoietic
      stem cell transplantation.
AB  - In a previous study, we noted wide inter-individual variability in drug
      interactions between voriconazole and tacrolimus, but that analysis did not take
      into account the routes of administration. In the present study, we analyzed
      interactions between these two drugs when both agents were administered orally
      after allogeneic hematopoietic stem cell transplantation (HSCT); the effect of
      plasma voriconazole levels on the magnitude of the drug interaction was also
      examined. Twenty-five allogeneic HSCT recipients were evaluated. Trough
      concentrations of tacrolimus were measured prior to, and periodically for 7-10
      days after, initiating voriconazole (400 mg/day) to determine the
      concentration/dose (C/D) ratio of tacrolimus. The median C/D ratio of tacrolimus
      increased significantly from 172.8 (range 28.6-1110.7) to 537.5 (range 127.8
      1933.3) (ng/mL)/(mg/kg) (P < 0.01) following initiation of voriconazole; the
      median increase was 138.8 % (range -32.0 to 685.7 %). The plasma concentration of
      voriconazole did not correlate with the increase of the tacrolimus C/D ratio (rho
      = 0.16, P = 0.44). These results indicate that oral voriconazole has a
      significant drug interaction with oral tacrolimus with a wide inter-individual
      variability, which cannot be explained by the bioavailability of voriconazole.
      Other possible mechanisms should be explored in future studies.

PMID- 22461035
TI  - Phylogeography of the Korean pine (Pinus koraiensis) in northeast Asia:
      inferences from organelle gene sequences.
AB  - Range-wide genetic variation of Korean pine (Pinus koraiensis) was assessed using
      maternally inherited mtDNA and paternally inherited cpDNA for 16 natural
      populations throughout northeast Asia in order to study its phylogeographical
      history during the Quaternary. The cpDNA variation indicated that there was no
      difference between populations on the Asian continent and those in the Japanese
      archipelago. In contrast, the mtDNA variation indicated that there was
      significant difference between the populations from the two regions, with each
      region having a different lineage. The continental populations exhibited no
      diversity in the mtDNA examined despite the species' current extensive range and
      large populations. Conversely, while the Korean pine is rare in Japan, the
      Japanese populations exhibited greater levels of mtDNA diversity (H (T) = 0.502).
      The higher mtDNA diversity and evidence from numerous Korean pine macrofossil
      remains dated to the Pleistocene and recovered various sites in Japan suggest
      that the Japanese archipelago once served as a refugium to a much larger Korean
      pine population with a more extensive range than is the case today. The presence
      of the single mtDNA haplotype across the Asian continent suggests that the
      present widespread populations could have expanded from a single refugium
      population after the last glacial periods.

PMID- 22461036
TI  - Assessment of the mass, length, center of mass, and principal moment of inertia
      of body segments in adult males of the brown anole (Anolis sagrei) and green, or
      carolina, anole (Anolis carolinensis).
AB  - This study provides a morphometric data set of body segments that are
      biomechanically relevant for locomotion in two ecomorphs of adult male anoles,
      namely, the trunk-ground Anolis sagrei and the trunk-crown Anolis carolinensis.
      For each species, 10 segments were characterized, and for each segment, length,
      mass, location of the center of mass, and radius of gyration were measured or
      calculated, respectively. The radii of gyration were computed from the moments of
      inertia by using the double swing pendulum method. The trunk-ground A. sagrei has
      relatively longer and stockier hindlimbs and forelimbs with smaller body than A.
      carolinensis. These differences between the two ecomorphs demonstrated a clear
      relationship between morphology and performance, particularly in the context of
      predator avoidance behavior, such as running or jumping in A. sagrei and crypsis
      in A. carolinensis. Our results provide new perspectives on the mechanism of
      adaptive radiation as the limbs of the two species appear to scale via linear
      factors and, therefore, may also provide explanations for the mechanism of
      evolutionary changes of structures within an ecological context.

PMID- 22461037
TI  - Live donor champion:  finding live kidney donors by separating the advocate from
      the patient.
AB  - BACKGROUND: Lack of education and reluctance to initiate a conversation about
      live donor kidney transplantation is a common barrier to finding a donor.
      Although transplant candidates are often hesitant to discuss their illness,
      friends or family members are often eager to spread awareness and are empowered
      by advocating for the candidates. We hypothesized that separating the advocate
      from the patient is important in identifying live donors. METHODS: We developed
      an intervention to train a live donor champion (LDC; a friend, family member, or
      community member willing to advocate for the candidate) for this advocacy role.
      We compared outcomes of 15 adult kidney transplant candidates who had no
      prospective donors and underwent the LDC intervention with 15 matched controls
      from our waiting list. RESULTS: Comfort in initiating a conversation about
      transplantation increased over time for LDCs. Twenty-five potential donors
      contacted our center on behalf of LDC participants; four participants achieved
      live donor kidney transplantation and three additional participants have donors
      in evaluation, compared with zero among matched controls (P < 0.001).
      CONCLUSIONS: Transplant candidates are ill equipped to seek live donors; by
      separating the advocate from the patient, understandable concerns about
      initiating conversations are reduced.

PMID- 22461038
TI  - V5-drainage-preserved right lobe grafts improve graft congestion for living donor
      liver transplantation.
AB  - BACKGROUND: Right lobe (RL) grafts without middle hepatic vein for living donor
      liver transplantation (LDLT) result in congestion of recipients' livers and
      sometimes in unfavorable postoperative course. This study aimed to evaluate the
      feasibility of our new V5-drainage-preserved RL (VP-RL) graft. METHODS: Based on
      a review of 49 donors' livers in a retrospective study using three-dimensional
      reconstruction-computed tomography volumetry, hepatic vein draining segment 4
      (V4) anatomy was classified into three types: inferior V4 dominant (A); superior
      V4 dominant (B); and umbilical vein to left hepatic vein dominant (C).
      Differences in functional graft volume (GV) and remnant liver volume (RV) between
      VP-RL and modified RL (M-RL) grafts with all three types were evaluated. In a
      prospective study of actual 15 LDLT, the outcome of venous reconstruction and
      postoperative parameters with VP-RL grafts compared with M-RL grafts was
      analyzed. RESULTS: In the retrospective study using three-dimensional
      reconstruction-computed tomography volumetry, in types B and C, functional GV of
      VP-RL was larger than that of M-RL (P<0.05) without impaired donors' functional
      RV, whereas functional RV in VP-RL was significantly decreased in type A
      (P<0.05). In the prospective study of actual 15 LDLT, using VP-RL with types B
      and C, size and number of venous reconstructions, and functional GV and
      postoperative parameters, such as postoperative serum total bilirubin levels and
      ascites volume, were significantly improved compared with those using M-RL
      (P<0.05). CONCLUSIONS: Using preoperative V4 anatomical classification, VP-RL
      graft procurement is a valuable strategy in RL-LDLT to improve postoperative
      course of both recipients and donors.

PMID- 22461039
TI  - Anti-inflammatory and immunomodulatory properties of azithromycin involved in
      treatment and prevention of chronic lung allograft rejection.
AB  - Chronic lung allograft rejection is the single most important cause of death in
      lung transplant recipients after the first postoperative year, resulting in a 5
      year survival rate of approximately 50%, which is far behind that of other solid
      organ transplantations. Spirometry is routinely used as a clinical marker for
      assessing pulmonary allograft function and diagnosing chronic lung allograft
      rejection after lung transplantation (LTx). As such, a progressive obstructive
      decline in pulmonary allograft function (forced expiratory volume in 1 sec
      [FEV1]) in absence of all other causes (currently defined as bronchiolitis
      obliterans syndrome [BOS]) is considered to reflect the evolution of chronic lung
      allograft rejection. BOS has a 5-year prevalence of approximately 45% and is
      thought to be the final common endpoint of various alloimmunologic and
      nonalloimmunologic injuries to the pulmonary allograft, triggering different
      innate and adaptive immune responses. Most preventive and therapeutic strategies
      for this complex process have thus far been largely unsuccessful. However, the
      introduction of the neomacrolide antibiotic azithromycin (AZI) in the field of
      LTx as of 2003 made it clear that some patients with established BOS might in
      fact benefit from such therapy due to its various antiinflammatory and
      immunomodulatory properties, as summarized in this review. Particularly in
      patients with an increased bronchoalveolar lavage neutrophilia (i.e., 15%-20% or
      more), AZI treatment could result in an increase in FEV1 of at least 10%. More
      recently, it has become clear that prophylactic therapy with AZI actually may
      prevent BOS and improve FEV1 after LTx, most likely through its interactions with
      the innate immune system. However, one should always be aware of possible adverse
      effects related to AZI when implementing this drug as prophylactic or long-term
      treatment. Even so, AZI therapy after LTx can generally be considered as safe.

PMID- 22461040
TI  - Organ donation and priority points in Israel:  an ethical analysis.
AB  - Israel's rates of organ donation have been one of the lowest among developed
      countries. An attempt to change this has led to the introduction of a pioneering
      new law, the Organ Transplant Act 2008, which came into effect in January 2010
      and sets out principles underlying a new policy in relation to the allocation of
      organs for transplantation. According to this policy, a person can gain priority
      points by signing a donor card, making a nondirected organ donation during their
      lifetime, or as a result of a first-degree relative signing a donor card, or
      consenting to procurement of organs after death. In this opinion piece, we argue
      that although this approach merits attention for its innovative aspects and its
      potential benefits, it raises some ethical difficulties. In particular, we
      discuss some problems of justice and fairness inherent in the system, focusing on
      inequalities because of the (a) number of relatives one might have, (b) the type
      of living donation one makes, (c) the potential for strategic behavior, and (d)
      problems regarding the consent of family members.

PMID- 22461042
TI  - Patient's age as a factor in the use of diagnostic tools and evidence based
      therapies in patients with heart failure.

PMID- 22461041
TI  - A single-dose study of denosumab in patients with various degrees of renal
      impairment.
AB  - This 16-week study evaluated pharmacokinetics and pharmacodynamics of denosumab
      in 55 subjects with renal function ranging from normal to dialysis-dependent
      kidney failure. Participants received a single 60-mg subcutaneous dose of
      denosumab. Kidney function groups were based on calculations using the Cockcroft
      Gault equation and U.S. Food and Drug Administration (FDA) guidance in place when
      the study was designed. Renal function did not have a significant effect on
      denosumab pharmacokinetics or pharmacodynamics. These findings suggest denosumab
      dose adjustment based on glomerular filtration rate is not required. Rapid
      decreases in serum C-telopeptide in all groups were sustained throughout the
      study. The most common adverse events were hypocalcemia (15%), pain in extremity
      (15%), and nausea (11%). Most adverse events were mild to moderate in severity.
      Calcium and vitamin D supplementation was not initially required by the study
      protocol, but was added during the trial. No subject who received adequate
      calcium and vitamin D supplementation became hypocalcemic. Seven subjects had
      nadir serum calcium concentrations between 7.5 and <8.0 mg/dL (1.9 and <2.0
      mmol/L), and 5 subjects (4 with advanced renal disease) had nadir serum calcium
      <7.5 mg/dL (<1.9 mmol/L). Two subjects (1 symptomatic, 1 asymptomatic) were
      hospitalized for intravenous calcium gluconate treatment. At the recommended
      dose, denosumab is a useful therapeutic option for patients with impaired renal
      function. Supplementation of calcium and vitamin D is strongly recommended when
      patients initiate denosumab therapy, particularly in patients with reduced renal
      function.

PMID- 22461043
TI  - QRS fragmentation: diagnostic and prognostic significance.
AB  - Fragmentation of QRS (fQRS) complex is an easily evaluated non-invasive
      electrocardiographic parameter. Fragmentation of narrow QRS is defined as
      presence of an additional R wave (R') or notching in the nadir of the S wave, or
      the presence of > 1 R' in 2 contiguous leads, corresponding to a major coronary
      artery territory on the resting 12-lead ECG. Fragmentation of wide complex QRS
      consists of various RSR patterns, with more than 2 R waves (R'') or more than 2
      notches in the R wave, or more than 2 notches in the downstroke or upstroke of
      the S wave. Presence of fQRS has been associated with alternation of myocardial
      activation due to myocardial scar and myocardial fibrosis. Initial studies
      reported higher sensitivity of fQRS than Q wave for detecting myocardial scar and
      postulated that the presence of fQRS could be a good predictor of cardiac events
      among the patients with coronary artery disease. The presence of fQRS has been
      investigated among the patients with ischemic and non-ischemic cardiomyopathy
      suggesting that this ECG parameter may affect prognosis and risk of sudden
      cardiac death, risk of implantable cardioverter-defibrillator therapy and
      response to cardiac resynchronization therapy. In addition, there is evidence
      that fQRS could play an important role as screening and prognostic tool among the
      patients with Brugada syndrome, long QT syndrome, arrhythmogenic right
      ventricular dysplasia and cardiac sarcoidosis. This paper reviews definition,
      diagnostic and prognostic value of fQRS in different patient populations.

PMID- 22461044
TI  - Anomalous origin of the right coronary artery from the left anterior descending
      artery: review of the literature.
AB  - Coronary artery anomalies that take place during fetal development are determined
      in approximately 1.3% of coronary angiograms. The right coronary artery
      originating from the left coronary system is an extremely rare variation of the
      single coronary artery anomaly in which the prognosis is usually benign provided
      that the anomalous vessel dose not pass between the aorta and the pulmonary
      artery. Anomalous right coronary artery anomaly has been rarely associated with
      other congenital cardiovascular anomalies such as transposition of the great
      vessels and tetralogy of Fallot. To date, a few attempts at classification have
      been made for coronary artery anomalies, but none of them seems comprehensive or
      practical for clinicians. The clinical significance of coronary anomalies is
      usually determined by underlying anatomic features of the wrong coronary origin
      and/or coronary atherosclerosis. Although coronary angiography is an important
      diagnostic method, new non-invasive methods such as coronary computed tomography
      angiography and cardiac magnetic resonance imaging have important roles to play
      in characterizing this coronary anomaly. It should be noted that the management
      strategy of these patients may vary based on clinical presentation, anatomical
      details and additional findings.

PMID- 22461045
TI  - Determination of right ventricular dysfunction using the speckle tracking
      echocardiography method in patients with obstructive sleep apnea.
AB  - BACKGROUND: The speckle tracking echocardiography (STE) method shows the presence
      of right ventricular (RV) dysfunction before the advent of RV failure and
      pulmonary hypertension in patients with cardiopulmonary disease. We aimed to
      assess subclinical RV dysfunction in obstructive sleep apnea (OSA) using the STE
      method. METHOD: Twenty-one healthy individuals and 58 OSA patients were included.
      According to severity as determined by the apnea-hypopnea index (AHI), OSA
      patients were examined in three groups: mild, moderate and severe. RV free wall
      was used in STE examination. RESULTS: Right ventricle strain (ST %) and systolic
      strain rate (STR-S 1/s) were decreasing along with the disease severity (ST -
      healthy: -34.05 +/- -4.29; mild: -31.4 +/- -5.37; moderate: -22.75 +/- -4.89;
      severe: -20.89 +/- -5.59; p < 0.003; STR-S - healthy: -2.93 +/- -0.64; mild: 
      2.85 +/- -0.73; moderate: -2.06 +/- -0.43; severe: -1.43 +/- -0.33; p < 0.03).
      Correlated with the disease severity, the RV early diastolic strain rate (STR-E)
      was decreasing and the late diastolic strain rate was increasing (STR-E -
      healthy: 2.38 +/- 0.63; mild: 2.32 +/- 0.84; moderate: 1.66 +/- 0.55; severe: 1
      +/- 0.54; p < 0.003; STR-A - healthy: 2.25 +/- 0.33; mild: 2.32 +/- 0.54;
      moderate: 2.79 +/- 0.66; severe: 3.29 +/- 0.54; p < 0.03). The STR-E/A ratio was
      found to be in a decreasing trend along with the disease severity (healthy: 1.08
      +/- 0.34; mild: 1.06 +/- 0.46; moderate: 0.62 +/- 0.22; severe: 0.34 +/- 0.23; p
      < 0.03). CONCLUSIONS: Subclinical RV dysfunction can be established in OSA
      patients even in the absence of pulmonary hypertension and pathologies which
      could have adverse effects on RV functions. In addition to the methods of
      conventional, Doppler and tissue Doppler echocardiography, using the STE method
      can determine RV dysfunction in the subclinical phase.

PMID- 22461046
TI  - Assessment of the relationship between non-dipping phenomenon and heart rate
      turbulence.
AB  - BACKGROUND: The aim of this cross-sectional study was to evaluate cardiac
      autonomic function by heart rate turbulence (HRT) indices in normotensive and
      hypertensive individuals with either non-dipper or dipper type circadian rhythm
      of blood pressure (BP). METHODS: A total of 122 patients were allocated into four
      groups: normotensive/dipper, n = 33; normotensive/non-dipper, n = 31;
      hypertensive/dipper, n = 29; and hypertensive/non-dipper, n = 29. HRT indices
      (turbulence slope [TS] and turbulence onset [TO]) were calculated from 24-h
      ambulatory electrocardiographic recordings. RESULTS: TS values were higher (TS =
      10.0 +/- 3.4 vs 8.0 +/- 1.5, p = 0.004) and TO values were lower (TO = -2.9 [
      3.6, -2.2] vs -2.0 [-2.3, -1.9], p = 0.037) in the dipper subgroup of
      normotensive cases than in the non-dipper subgroup of normotensive cases.
      Similarly, TS values were higher (TS = 8.4 +/- 3.5 vs 6.2 +/- 2.9, p = 0.012) and
      TO values were lower (TO = -2.1 [-3.4, -2.0] vs -1.6 [-1.9, -0.2], p = 0.003) in
      the dipper subgroup of hypertensive cases than in the non-dipper subgroup of
      hypertensive cases. Spearman's correlation analyses revealed a high positive
      correlation between percentage of dipping and TS (r = 0.600, p = 0.001) and a
      higher negative correlation between percentage of dipping and TO (r = -0.653, p =
      0.001). CONCLUSIONS: Blunting of the nocturnal fall in BP is associated with
      impaired HRT indices in both normotensive and hypertensive groups.

PMID- 22461047
TI  - Age-related gap in the management of heart failure patients. The National Project
      of Prevention and Treatment of Cardiovascular Diseases--POLKARD.
AB  - BACKGROUND: Heart failure (HF) is strongly associated with aging. It affects 10
      12% of patients older than 80 years, with five-year overall mortality after first
      hospitalization for HF being as high as 81%. The main objective of this study was
      to assess the diagnosis and treatment of HF in hospitalized octogenarians
      compared to younger subjects. METHODS: The survey was performed among a random
      sample of all Polish hospitals and in all academic centers, as part of the
      National Project of Prevention and Treatment of Cardiovascular Diseases in Poland
      -- POLKARD. Using a questionnaire-based method, hospital documentation of the
      last five patients with diagnosed HF was reviewed. Eventually, in 2005, HF
      patients of 259 internal medicine and cardiology hospital wards, including 260
      very elderly patients, were selected to the study. RESULTS: The mean age of the
      1,289 studied patients was 69.8 +/- 11.4 years (age range: 26-96 years), 57.8%
      were males, and 80.1% were in NYHA class III or IV. Echocardiography was
      performed in 41.7% of octogenarians in comparison with 58.7% of those categorized
      as younger elderly, i.e. 60-79 years, and 75.2% of patients aged below 60 years
      (p < 0.0001). The most prescribed drugs in very elderly patients were diuretics
      (86.9%, p = 0.005) and ACE-I (81.9%), while only 61.5% used beta-blockers (p <
      0.0001). In stepwise logistic regression analysis, hypertension, history of
      myocardial infarction and admission to cardiology ward were positively associated
      with beta-blocker and ACE-I (or ARB) therapy, while older age and pulmonary
      diseases (COPD or asthma) were related to their non-prescription. CONCLUSIONS:
      Despite significant progress in HF management, there is still a need for an
      improvement in the medical care of very elderly patients. The major obstacles
      seem to be advanced age and the presence of coexistent pulmonary diseases.
      Therefore, the participation of geriatricians and pulmonologists should be
      recommended in caring for octogenarians with HF.

PMID- 22461048
TI  - How effective are continuous flow left ventricular assist devices in lowering
      high pulmonary artery pressures in heart transplant candidates?
AB  - BACKGROUND: Pulmonary hypertension (PH) is considered a risk factor for morbidity
      and mortality in patients undergoing heart transplantation. Medical therapy with
      oral and pharmacologic agents is not always effective in reducing pulmonary
      artery (PA) pressures. Left ventricular assist devices (LVADs) have been used to
      reduce PA pressures in cases of PH unresponsive to medical therapy. METHODS AND
      RESULTS: Our study sought to evaluate the effectiveness of axial- and centrifugal
      continuous flow LVADs in reversing PH in heart transplant candidates.
      Hemodynamics were assessed pre- and post-operatively in nine patients undergoing
      HeartMate II and six patients undergoing HeartWare continuous flow LVADs. Mean PA
      pressures were reduced from 31.9 +/- 10.6 mm Hg to 22.1 +/- 6.6 mm Hg (p =
      0.001), and pulmonary vascular resistance was reduced from 3.08 +/- 1.6 mm Hg to
      1.8 +/- 1.0 mm Hg (p = 0.007). This improvement was seen within seven days of
      LVAD implantation. Three of 15 patients were successfully transplanted, with 100%
      survival at an average of 199 days post-transplant. CONCLUSIONS: The results of
      this study suggest that both axial- and centrifugal-continuous flow LVADs are
      effective in immediately lowering PA pressures in heart transplant candidates
      with PH.

PMID- 22461049
TI  - Molecular diagnostics of families with long-QT syndrome.
AB  - The Department of Pediatric Cardiology, Medical University of Silesia in Katowice
      Ligota, studied 24 patients with clinically diagnosed (using ECG) long-QT
      syndrome (LQTS) in 18 cases. Nine patients were diagnosed with LQT1 and nine with
      LQT2. The other six individuals were healthy, with no symptoms characteristic for
      prolonged QT syndrome, but came from families with confirmed disease occurrence.
      The study was conducted on members of four families. In order to search for
      mutations (using mSSCP and sequencing), genomic DNA was obtained from patients to
      determine the expression levels of the genes KCNQ1 and KCNH2 (HERG), involved in
      the occurrence of clinical signs of disease. Total RNA was extracted from
      peripheral blood. Consent to the use of blood samples of patients had been given
      by the Bioethics Commission of the Medical University of Silesia. mSSCP analysis
      and sequencing did not confirm the occurrence of mutations in KCNQ1 and HERG
      associated with the occurrence of LQTS. Analysis of gene expression profile of
      KCNQ1 and HERG confirmed the presence of disease in people with a known clinical
      diagnosis. Overexpression, as well as reduced expression, was observed for the
      examined genes. KCNQ1 was inhibited in two families, whereas HERG was reduced in
      one and overexpressed in the other. Gene expression profile analysis showed
      abnormal expressions of KCNQ1 and HERG in healthy subjects, which may be a sign
      of predisposition to develop the disease. The novelty of our study involved the
      use of total mRNA isolated from human peripheral blood, and the very limited
      evidence in the literature to date regarding the assessment of gene expression
      profile of HERG and KCNQ1 in relation to the presence of prolonged QT syndrome.

PMID- 22461050
TI  - Thrombolytic effect of streptokinase infusion assessed by ST-segment resolution
      between diabetic and non-diabetic myocardial infarction patients.
AB  - BACKGROUND: Recently, it has been hypothesized that type 2 diabetes might
      interfere with acute intravenous thrombolysis effectiveness as estimated by
      angiographic or electrocardiographic criteria. In our study, we compared the
      thrombolytic effect of streptokinase infusion between diabetic and non-diabetic
      myocardial infarction (MI) patients. METHODS: In a prospective interventional
      study, 240 consecutive patients who were admitted to the emergency ward and
      diagnosed with ST-elevation MI (STEMI) were enroled and classified into diabetics
      (n = 85) and non-diabetics (n = 155). Streptokinase was given to each patient at
      a dose of 1.5 million units in 1 h. Twelve-lead ECG was recorded immediately
      before the start of thrombolytic therapy and at 180 min afterwards for the
      patients with STEMI. The ST-segment elevation resolution was calculated and
      stratified as complete resolution ( > 70% ST-resolution), partial resolution (30
      70% ST-resolution), or failed resolution ( < 30% ST-resolution). RESULTS:
      Complete ST-resolution occurred in 31.6% of diabetic and 51.0% of non-diabetic
      patients, respectively (p < 0.001). The incidence of partial ST-resolution in
      diabetic and non-diabetic patients was 40.5% and 40.0%, whereas 27.8% of patients
      in the diabetic group and 9.0% of patients in the non-diabetic group showed
      failed ST resolution. ST-resolution was independent of the location of MI.
      Multivariate analysis showed that diabetes mellitus, as well as higher Killip
      class and lower ejection fraction, could effectively predict ST-resolution
      failure. CONCLUSIONS: Failure of ST-segment resolution 180 min after
      streptokinase infusion is notably higher in diabetic vs non-diabetic patients.
      This failure rate is correlated with higher Killip class and lower ejection
      fraction.

PMID- 22461051
TI  - All-cause readmission and repeat revascularization after percutaneous coronary
      intervention.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is one of the most
      frequently performed cardiac interventions. However, there is limited data
      regarding the cause of recurrent hospitalization and repeat revascularization.
      The aim of this study was to assess re-hospitalization and repeat
      revascularization within 30 days of the initial hospitalization for PCI, using
      data from Opolskie Voivodeship, National Health Fund (NHF) Registry. METHODS: The
      study population consisted of all PCI patients treated in three interventional
      cardiology laboratories in Opolskie Voivodeship in Poland between 1 July 2008 and
      30 June 2009. All PCI patients who died during the initial hospitalization or who
      were transferred to other units were excluded from the analysis. The study end
      point comprised 30 day all-cause readmission and repeat revascularization.
      RESULTS: A total of 2,039 PCI patients were included in the analysis. The all
      cause 30-day readmission rate was 14.6%. The 30-day readmission rate of acute
      coronary syndrome (ACS) patients was significantly higher compared to the stable
      coronary disease patients (ACS 15.8%, non-ACS 10.7%, p = 0.008). The 30-day
      readmission rate did not differ between the three cardiac laboratories.
      Approximately half (46.2%) of all readmitted patients underwent a repeat
      revascularization procedure, mainly in the form of PCI. The overall all-cause 30
      day mortality rate was 0.8%. Compared to the PCI patients who did not require
      readmission, the readmitted patients had a significantly higher all-cause 30-day
      mortality rate (3.6% vs 0.3%, p < 0.001). CONCLUSIONS: Almost one in seven PCI
      patients requires readmission within 30 days of hospital discharge. Approximately
      50% of all readmitted PCI patients resulted in a repeat revascularization
      procedure. PCI patients who were readmitted within 30 days of an index PCI
      procedure had a significantly higher all-cause 30-day mortality rate.

PMID- 22461052
TI  - Comparison of mean platelet volume values among different causes of pulmonary
      hypertension.
AB  - BACKGROUND: Pulmonary hypertension is caused by a heterogenous group of disorders
      with diverse pathophysiological mechanisms, with ultimate structural changes in
      the pulmonary vascular bed. Platelet activation plays an important role in the
      development of pulmonary arterial hypertension, while it is unknown whether it
      contributes to pathogenesis in other conditions. We aimed to investigate platelet
      activation in different causes of pulmonary hypertension by means of mean
      platelet volume measurement. METHODS: A total of 67 patients with different
      causes of pulmonary hypertension, and 31 controls, were retrospectively reviewed.
      Patients with pulmonary hypertension were further grouped according to underlying
      disease, including pulmonary arterial hypertension, pulmonary hypertension due to
      left ventricular failure, and pulmonary hypertension due to chronic obstructive
      pulmonary disorder. All patients and controls past medical data, admission
      echocardiograms and complete blood counts were reviewed. RESULTS: Patients with
      pulmonary hypertension had higher mean platelet volume levels compared to healthy
      controls (8.77 +/- 1.18 vs 7.89 +/- 0.53; p < 0.001), and statistical
      significance was still present when pulmonary arterial hypertension patients were
      not included in the pulmonary hypertension group (8.59 +/- 1.23 vs 7.89 +/- 0.53;
      p < 0.001). Among patients with pulmonary hypertension, the pulmonary arterial
      hypertension group and the pulmonary hypertension due to left ventricular failure
      group had higher mean platelet volumes compared to healthy controls. Mean
      platelet volume did not correlate with pulmonary artery pressure. CONCLUSIONS:
      Our results indicate that mean platelet volume is not only elevated in pulmonary
      arterial hypertension, but also due to other causes of pulmonary hypertension.

PMID- 22461053
TI  - An unusual presentation of pericardial cyst: recurrent syncope in a young
      patient.
AB  - Although pericardial cysts are generally benign structures and detected
      incidentally, they may be associated with life-threatening complications. We
      present the case of a 24 year-old man with a giant hemorrhagic pericardial cyst
      diagnosed after evaluation for recurrent syncope which caused compression of the
      right ventricle. Spontaneous hemorrhage into a pericardial cyst is an extremely
      rare event, and to our knowledge this is the first case in which a pericardial
      cyst has been shown to cause recurrent syncope.

PMID- 22461054
TI  - Extraction of abandoned, potentially dangerous lead with uncovered proximal
      ending: a case report and method description.
AB  - In this study, we present the case of the extraction of a non-functioning,
      abandoned, chronically implanted nine year-old lead with proximal extended frayed
      ending, displaced spontaneously into the subclavian vein. The seemingly
      inaccessible lead was extracted from the body using the femoral approach. The
      lead was looped with a pig-tail catheter, standard guide-wire, and basket Dotter
      catheter, and the proximal ingrown ending was liberated. Finally, it was grasped
      with a basket catheter and its tip was liberated using oblique cut rotated
      internal sheath of a Femoral Working Station: using it as a Byrd dilator designed
      for subclavian approach. An additional difficulty was the risk of dislodging the
      correct endocardial lead in the pacemaker-dependent patient. The procedure
      indicates the necessity for the production of longer Byrd dilators designed for
      the femoral approach.

PMID- 22461055
TI  - The use of Amplatzer Vascular Plug((r)) to treat coronary steal due to unligated
      thoracic side branch of left internal mammary artery: four year follow-up
      results.
AB  - Left internal mammary artery (LIMA) is the most commonly used graft during
      coronary bypass surgery. LIMA side branches are clipped during surgery in order
      to prevent coronary steal. In cases of patent LIMA side branches, there are
      differingapproaches. Herein, we report a case with patent thoracic side branch of
      LIMA graft, occlusion of this side branch by Amplatzer Vascular Plug because of
      documented myocardial ischemia, and long term follow-up results.

PMID- 22461056
TI  - Late diagnosis of congenital cardiovascular defect.
AB  - Coarctation of the aorta (CoA) is a common congenital anomaly that is usually
      treated in infancy or childhood. Adult patients with coarctation have a high
      incidence of associated cardiac disorders, including valve diseases, atrial
      fibrillation and ischemic heart disease. Most patients with uncorrected CoA die
      before reaching the age of 50 from complications such as myocardial infarction,
      intracranial hemorrhage, congestive heart failure (HF), infective endocarditis or
      aortic dissection. We report the case of a 65 year-old woman admitted to hospital
      with symptoms of heart failure NYHA class IV. She had been treated for several
      years for refractory arterial hypertension and concomitant stenocardia (II CCS).
      The symptoms of HF had been increasing over several months. Outpatient
      echocardiography examination revealed significant, increasing mitral and
      tricuspid valve regurgitation with progressive left ventricular dysfunction. The
      patient was referred for surgical repair of the mitral and tricuspid valves. In
      hospital echocardiography and angiography revealed descending aorta discontinuity
      at the level of the aortic isthmus. This congenital disease revealed during
      hospitalization was determined to be the underlying cause of all the symptoms the
      patient presented. Due to the clinical status of the patient, she was discharged
      from surgical procedures and put on medication.

PMID- 22461057
TI  - A rare congenital anomaly: pulmonary atresia and abnormal origin of right
      pulmonary artery.

PMID- 22461058
TI  - Stressed at the dentist? A case of tako-tsubo.

PMID- 22461059
TI  - Paradoxical atrial undersensing by a dual chamber pacemaker during atrial
      fibrillation.
AB  - This report describes paradoxical atrial undersensing by a dual chamber pacemaker
      in a patient with paroxysmal atrial fibrillation. Atrial undersensing was present
      only when the device was programmed to a high sensitivity but sensing normalized
      when a lower sensitivity was programmed. This unusual response should be
      differentiated from the recently documented lock-in behavior of pacemakers
      delivering managed ventricular pacing.

PMID- 22461060
TI  - New devices for very long-term ECG monitoring.
AB  - Present day 24-h Holter monitors have been shown to miss many arrhythmias that
      may occur infrequently or under specific circumstances. The advancement in
      electronic and adhesive technologies have enabled the development of first
      generation wearable long-term 14-day patch ECG monitors that attach directly to
      the skin and require no electrodes and wires to operate. This new technology is
      unobtrusive to the patients and offers them unprecedented mobility. It enables
      very long-term monitoring of critical patients while they are carrying out daily
      activities. The monitors are waterproof, offer good adhesion to the skin and can
      operate as either recorders or wireless streaming devices.

PMID- 22461061
TI  - Autonomic dysreflexia: an important cardiovascular complication in spinal cord
      injury patients.
AB  - Autonomic dysreflexia (AD) is a life-threatening complication of spinal cord
      injury (SCI) at T6 or above that results in an uncontrolled sympathetic discharge
      in response to noxious stimuli. It is a symptom complex characterized by a lethal
      rise in blood pressure with dangerous consequences. Autonomic dysreflexia is
      often secondary to urological, gastrointestinal, or gynecological problems or
      manipulations. Early recognition and prompt treatment of AD is vital to prevent
      complications, including death. Its management starts primarily with its
      prevention. Easy measures can avoid this high risk event, and physicians should
      be aware of the simple procedures and the possible treatment cascade that could
      be undertaken. The purpose of this systematic review is to review the clinical
      data on the mechanisms and pathophysiology of this condition and the clinical
      evidence about the various strategies currently used to prevent and manage AD in
      the SCI population; and to improve awareness of AD among cardiologists, family
      physicians and medical personnel in the emergency department.

PMID- 22461062
TI  - Henry N. Neufeld: the art of politics in cardiology.

PMID- 22461063
TI  - Randomised health services studies.
AB  - The randomised controlled (or clinical) trial (RCT) is recognized as the most
      valid among the study designs. The use of RCT in research is widespread and well
      formalised. In contrast, implementations of new methods and policies in routine
      health care are commonly lacking a formalised design, impairing the ability to
      evaluate and improve health care. Use of experimental designs in health care is
      possible at the implementation phase of clinical or preventive action or more
      broad process-of-care. We propose the terminology randomised health services
      studies (RHS) to denote the use of a randomised design with observations in
      routine health care, regardless of whether randomisation is done at individual,
      population or process level. In contrast to RCT, the RHS should be based on the
      same regulative actions, funding mechanisms and ethical framework as routine
      health care itself. This commentary discusses the different basis,
      practicalities, and formalities that distinguish the RHS from the RCT.
      Development of a formalised framework for RHS, including distinct registration,
      could contribute to an increased use of valid methods in effectiveness research,
      thus gaining better and more direct evidence on routine medical practice.

PMID- 22461064
TI  - Elevated oxidative stress and decreased antioxidant function in the human
      hippocampus and frontal cortex with increasing age: implications for
      neurodegeneration in Alzheimer's disease.
AB  - Oxidative stress and mitochondrial damage are implicated in the evolution of
      neurodegenerative diseases. Increased oxidative damage in specific brain regions
      during aging might render the brain susceptible to degeneration. Previously, we
      demonstrated increased oxidative damage and lowered antioxidant function in
      substantia nigra during aging making it vulnerable to degeneration associated
      with Parkinson's disease. To understand whether aging contributes to the
      vulnerability of brain regions in Alzheimer's disease, we assessed the oxidant
      and antioxidant markers, glutathione (GSH) metabolic enzymes, glial fibrillary
      acidic protein (GFAP) expression and mitochondrial complex I (CI) activity in
      hippocampus (HC) and frontal cortex (FC) compared with cerebellum (CB) in human
      brains with increasing age (0.01-80 years). We observed significant increase in
      protein oxidation (HC: p = 0.01; FC: p = 0.0002) and protein nitration (HC: p =
      0.001; FC: p = 0.02) and increased GFAP expression (HC: p = 0.03; FC: p = 0.001)
      with a decreasing trend in CI activity in HC and FC compared to CB with
      increasing age. These changes were associated with a decrease in antioxidant
      enzyme activities, such as superoxide dismutase (HC: p = 0.005), catalase (HC: p
      = 0.02), thioredoxin reductase (FC: p = 0.04), GSH reductase (GR) (HC: p =
      0.005), glutathione-s-transferase (HC: p = 0.0001; FC: p = 0.03) and GSH (HC: p =
      0.01) with age. However, these parameters were relatively unaltered in CB. We
      suggest that the regions HC and FC are subjected to widespread oxidative stress,
      loss of antioxidant function and enhanced GFAP expression during aging which
      might make them more susceptible to deranged physiology and selective neuronal
      degeneration.

PMID- 22461065
TI  - Using graded response model for the prediction of prostate cancer risk.
AB  - Disease risk-associated single nucleotide polymorphisms (SNPs) identified from
      genome-wide association studies (GWAS) have the potential to be used for disease
      risk prediction. An important feature of these risk-associated SNPs is their weak
      individual effect but stronger cumulative effect on disease risk. To date, a
      stable summary estimate of the joint effect of genetic variants on disease risk
      prediction is not available. In this study, we propose to use the graded response
      model (GRM), which is based on the item response theory, for estimating the
      individual risk that is associated with a set of SNPs. We compare the GRM with a
      recently proposed risk prediction model called cumulative relative risk (CRR).
      Thirty-three prostate cancer risk-associated SNPs were originally discovered in
      GWAS by December 2009. These SNPs were used to evaluate the performance of GRM
      and CRR for predicting prostate cancer risk in three GWAS populations, including
      populations from Sweden, Johns Hopkins Hospital, and the National Cancer
      Institute Cancer Genetic Markers of Susceptibility study. Computational results
      show that the risk prediction estimates of GRM, compared to CRR, are less biased
      and more stable.

PMID- 22461066
TI  - Mouse intragastric infusion (iG) model.
AB  - Direct intragastric delivery of a diet, nutrient or test substance can be
      achieved in rodents (mice and rats) on a long-term (2-3 months) basis using a
      chronically implanted gastrostomy catheter and a flow-through swivel system. This
      rodent intragastric infusion (iG) model has broad applications in research on
      food intake, gastrointestinal (GI) physiology, GI neuroendocrinology, drug
      metabolism and toxicity, obesity and liver disease. It achieves maximal control
      over the rate and pattern of delivery and it can be combined with normal ad
      libitum feeding of solid diet if so desired. It may be adopted to achieve
      infusion at other sites of the GI system to test the role of a bypassed GI
      segment in neuroendocrine physiology, and its use in genetic mouse models
      facilitates the genetic analysis of a central question under investigation.

PMID- 22461067
TI  - Cryoinjury as a myocardial infarction model for the study of cardiac regeneration
      in the zebrafish.
AB  - The zebrafish heart has the capacity to regenerate after ventricular resection.
      Although this regeneration model has proved useful for the elucidation of certain
      regeneration mechanisms, it is based on the removal of heart tissue rather than
      on tissue damage. We recently characterized the cellular response and
      regenerative capacity of the zebrafish heart after cryoinjury (CI), an
      alternative procedure that more closely models the pathophysiological process
      undergone by the human heart after myocardial infarction (MI). After anesthesia,
      localized CI with a liquid nitrogen-cooled copper probe induced damage in 25% of
      the ventricle, in a procedure requiring <5 min. Here we present a detailed
      description of the technique, which provides a valuable system for the study of
      the mechanisms of heart regeneration and scar removal after MI in a versatile
      vertebrate model.

PMID- 22461068
TI  - Inducing nonsense suppression by targeted pseudouridylation.
AB  - Isomerization from uridine to pseudouridine (pseudouridylation) is largely
      catalyzed by a family of small ribonucleoproteins called box H/ACA RNPs, each of
      which contains one unique small RNA-the box H/ACA RNA. The specificity of the
      pseudouridylation reaction is determined by the base-pairing interactions between
      the guide sequence of the box H/ACA RNA and the target sequence within an RNA
      substrate. Thus, by creating a new box H/ACA RNA harboring an artificial guide
      sequence that base-pairs with the substrate sequence, one can site-specifically
      introduce pseudouridines into virtually any RNA (e.g., mRNA, ribosomal RNA, small
      nuclear RNA, telomerase RNA and so on). Pseudouridylation changes the properties
      of a uridine residue and is likely to alter the role of its corresponding RNA in
      certain cellular processes, thereby enabling basic research into the effects of
      RNA modifications. Here we take a TRM4 reporter gene (also known as NCL1) as an
      example, and we present a protocol for designing a box H/ACA RNA to site
      specifically pseudouridylate TRM4 mRNA. Disease-related mutation can result in
      early termination of translation by creating a premature termination codon (PTC);
      however, pseudouridylation at the PTC can suppress this translation termination
      (nonsense suppression). Thus, the experimental procedures described in this
      protocol may provide a novel way to treat PTC-related diseases. This protocol
      takes 10-13 d to complete.

PMID- 22461069
TI  - Using bleach-chase to measure protein half-lives in living cells.
AB  - Protein removal has a central role in numerous cellular processes. Obtaining
      systematic measurements of multiple protein removal rates is necessary to
      understand the principles that govern these processes, but it is currently a
      major technical challenge. To address this, we developed 'bleach-chase', a
      noninvasive method for measuring the half-lives of multiple proteins at high
      temporal resolution in living cells. The method uses a library of annotated human
      reporter cell clones, each with a unique fluorescently tagged protein expressed
      from its native chromosomal location. In this protocol, we detail a simple
      procedure that bleaches the cells and uses time-lapse fluorescence microscopy and
      automated image analysis to systematically measure the half-life dynamics of
      multiple proteins. The duration of the protocol is 4-5 d. The method may be
      applicable to a wide range of fluorescently tagged proteins and cell lines.

PMID- 22461070
TI  - Cyclophane size drives the photochemical behaviour of benzophenone.
AB  - A new series of all-heterahomocalixarene-type structures was prepared. The new
      hetera[2(n)]metacyclophanes obtained contain a benzophenone moiety as photoactive
      component. Although both forms possess identical building blocks and differ only
      in ring size, they are markedly different in photochemical reactivity. The
      cyclophane size is the driving force for the photochemical behaviour of the
      benzophenone.

PMID- 22461071
TI  - Acanthocephalan parasites: help or burden in gammarid amphipods exposed to
      cadmium?
AB  - We investigated the influence of the acanthocephalan parasite Polymorphus minutus
      on the mortality of its intermediate host, Gammarus roeseli, exposed to cadmium,
      by the measure of LC(50-96h) values as well as the bioaccumulation of cadmium
      both in the host and in its parasite. LC(50) results revealed that infected G.
      roeseli males died less under cadmium stress than uninfected ones; while the
      converse has been observed in females. Cadmium resistance of infected males could
      be explained by a weaker bioconcentration factor (BCF) than in females. The lower
      BCF in infected individuals was closely related with an uptake of cadmium by P.
      minutus in its host. Nevertheless, although infected females had both weaker BCF
      and cadmium concentration in their body, the presence of P. minutus did not
      induce lower mortality than uninfected females. On the contrary, their
      sensitivity to cadmium was increased by the presence of P. minutus. We discuss
      the hypothesis that differences of mortality between uninfected and infected
      gammarids could be explained by a difference of cadmium bioconcentration in host,
      and by the cadmium bioaccumulation in the parasite. Indeed, results suggested
      that P. minutus could help G. roeseli to face with stress, what contributed to
      keep the host alive and favour the parasite transmission.

PMID- 22461072
TI  - Disruption of oligodendrocyte gap junctions in experimental autoimmune
      encephalomyelitis.
AB  - Gap junctions (GJs) are vital for oligodendrocyte survival and myelination. In
      order to examine how different stages of inflammatory demyelination affect
      oligodendrocyte GJs, we studied the expression of oligodendrocytic connexin32
      (Cx32) and Cx47 and astrocytic Cx43 in the experimental autoimmune
      encephalomyelitis (EAE) mouse model of multiple sclerosis (MS) induced by
      recombinant myelin oligodendrocyte glycoprotein. EAE was characterized by
      remissions and relapses with demyelination and axonal loss. Formation of GJ
      plaques was quantified in relation to the lesions and in normal appearing white
      matter (NAWM). During acute EAE at 14 days postimmunization (dpi) both Cx47 and
      Cx32 GJs were severely reduced within and around lesions but also in the NAWM.
      Cx47 was localized intracellularly in oligodendrocytes while protein levels
      remained unchanged, and this redistribution coincided with the loss of Cx43 GJs
      in astrocytes. Cx47 and Cx32 expression increased during remyelination at 28 dpi
      but decreased again at 50 dpi in the relapsing phase. Oligodendrocyte GJs
      remained reduced even in NAWM, despite increased formation of Cx43 GJs toward
      lesions indicating astrogliosis. EAE induced in Cx32 knockout mice resulted in an
      exacerbated clinical course with more demyelination and axonal loss compared with
      wild-type EAE mice of the same backcross, despite similar degree of inflammation,
      and an overall milder loss of Cx47 and Cx43 GJs. Thus, EAE causes persistent
      impairment of both intra- and intercellular oligodendrocyte GJs even in the NAWM,
      which may be an important mechanism of MS progression. Furthermore, GJ deficient
      myelinated fibers appear more vulnerable to CNS inflammatory demyelination.

PMID- 22461073
TI  - A new statistical decision rule for single-arm phase II oncology trials.
AB  - Most single-arm phase II clinical trials compare the efficacy of a new treatment
      with historical controls through statistical hypothesis testing. One major
      problem with such a comparison is that the efficacy of the historical control is
      treated as a known constant, whereas in reality, it is never precisely known.
      This partially explains why many "Go" decisions made in single-arm phase II
      trials are shown to be incorrect in phase III trials. In this paper, we propose a
      new decision rule for an improved transitional decision for single-arm phase II
      oncology clinical trials with binary endpoints. This new decision rule is jointly
      based on the p value and a new statistical index named the testing confidence
      value. The testing confidence value reflects the uncertainty associated with the
      null value in the hypothesis testing of single-arm trials. Simulations are used
      to evaluate the operating characteristics of the new decision rule in comparison
      with the traditional decision rule and a widely used Bayesian decision rule. The
      application of the new decision rule is illustrated using a clinical trial on
      marginally resectable pancreatic cancer. A webpage
      http://www.yiyichenbiostatistics.com/TCV.html is available for readers to
      interactively compute the testing confidence value and to find the suggested
      decision based on the new decision rule. 

PMID- 22461075
TI  - An unusual cause of spinal bone loss detected by DXA scanning.
AB  - Routine DXA scanning in a 68-year-old asymptomatic man undergoing long-term
      bisphosphonate treatment for osteogenesis imperfecta showed unexplained loss of
      bone mineral density in two lumbar vertebrae. Subsequent radiographs revealed a
      14-cm abdominal aortic aneurysm eroding the vertebrae. The importance of
      reviewing all the vertebrae in DXA scans is emphasized, and reasons for the
      absence of symptoms suggested.

PMID- 22461074
TI  - Depressive symptoms and rates of bone loss at the hip in older men.
AB  - In this prospective cohort study, depressive symptoms were associated with higher
      rates of bone loss in older men. Poorer performance on physical function tests
      partly explained the association between depressive symptoms and bone loss,
      suggesting that efforts to increase exercise and improve physical performance in
      depressed men may be beneficial. INTRODUCTION: The aim of this study was to
      ascertain whether depressive symptoms are associated with increased rates of bone
      loss at the hip in older men. METHODS: A population-based prospective cohort
      study of 2,464 community-dwelling men, aged 68 and older, enrolled in the
      Osteoporosis in Men Sleep Ancillary Study had depressive symptoms assessed by the
      Geriatric Depression Scale (GDS). Subjects were categorized as depressed if GDS
      >=6 at the initial examination. Bone mineral density (BMD) at the hip was
      measured using dual-energy X-ray absorptiometry at the initial and follow-up
      examination (average 3.4 years between exams). Use of antidepressant medications
      was assessed by interview and verified from medication containers at the two
      examinations. A computerized dictionary was used to categorize type of
      medication. RESULTS: In a base model adjusted for age, race/ethnicity, and clinic
      site, the mean total hip BMD decreased 0.70 %/year in 136 men with a GDS score of
      >=6 compared to 0.39 %/year in 2,328 men with a GDS score of <6 (p = 0.001).
      Walking speed and timed chair stand partly explained the association between
      depressive symptoms and rates of bone loss. CONCLUSION: Depression, as defined by
      a score of 6 or greater on the Geriatric Depression Scale, is associated with an
      increased rate of bone loss at the hip in this cohort of older men. Adjustment
      for walking speed and timed chair stand attenuated the strength of the
      association, suggesting that differences in physical functioning do partially
      explain the observed association.

PMID- 22461076
TI  - The TONIC trial: a step forward in treating pediatric nonalcoholic fatty liver
      disease.

PMID- 22461077
TI  - Antifibrotic role of macrophage migration inhibitory factor: discovery of an
      unexpected function.

PMID- 22461078
TI  - Diabetes and hepatocellular cancer risk: not only a matter of hyperglycemia.

PMID- 22461079
TI  - Extracellular proteins from Lactobacillus plantarum BMCM12 prevent adhesion of
      enteropathogens to mucin.
AB  - The aim of this study was to study the interference of the extracellular proteins
      produced by Lactobacillus plantarum BMCM12 with the adhesion of some well-known
      gut pathogens. The extracellular proteins secreted by L. plantarum BMCM12 in MRS
      broth were precipitated, resolved by SDS-PAGE, and identified by tandem mass
      spectrometry. Discordances between the observed and the theoretical molecular
      masses of several proteins suggested the presence of protein glycosylation,
      corroborated with specific glycoprotein staining after protein de-glycosylation
      using trifluoromethanesulfonic acid. Experiments of exclusion, competition, or
      prevention of the pathogen adhesion to mucin were performed using BMCM12
      extracellular proteins, using Escherichia coli LMG2092 and Salmonella enterica
      subsp. enterica LMG15860. Extracellular proteins from BMCM12 reduced
      significantly the adhesion of the pathogens when they were added prior to
      adhesion assays. These proteins play thus important roles in preventing pathogen
      adhesion to the mucin layer.

PMID- 22461080
TI  - Sulfoximines: a reusable directing group for chemo- and regioselective ortho C-H
      oxidation of arenes.
AB  - Sulfoximines direct: a new protocol for the chemo- and regioselective ortho C-H
      acetoxylation of arenes in N-benzoylated sulfoximines is reported. The
      sulfoximine directing group is easily detached from the C-H oxidation product
      through acid-promoted hydrolysis, isolated, and reused. The meta-substituted
      phenols are synthesized following this strategy and the stereointegrity of the
      sulfoximine is preserved in this transformation. C(sp(3))-H acetoxylation of the
      methyl group is also demonstrated.

PMID- 22461081
TI  - Extending homologous sequence based on the single gene mutants by one-step PCR
      for efficient multiple gene knockouts.
AB  - Multiple gene knockouts play an important role in metabolic engineering. The
      flanked homology length, homologous to the region adjacent to the target gene, of
      the knockout fragments has a great effect on the efficiency of multiple gene
      knockouts, whereas the existing gene knockout methods can only supply a very
      short homology. This article presents a strategy of easily extending homologous
      sequence based on the available strain library through one-step PCR amplification
      (the one-step PCR method). In this approach, the library of single gene mutants
      was used as the templates for PCR to amplify knockout fragments. Thus, the
      flanked homology can be extended as long as possible by designing primers
      upstream and downstream far from the target gene. Based on the one-step PCR
      method, we studied the effect of the homology length and the number of mutations
      on the efficiency of multiple gene knockouts. Our results indicated that the one
      step PCR method permitted rapid and efficient construction of multiple mutants
      continuously or simultaneously, and a length of 200-300 bp homologous sequence
      was equal for multiple gene knockouts.

PMID- 22461082
TI  - Highly hydrophilic copolymers of N,N-dimethylacrylamide, acrylamido-2
      methylpropanesulfonic acid, and ethylenedimethacrylate: nanoscale morphology in
      the swollen state and use as exotemplates for synthesis of nanostructured ferric
      oxide.
AB  - The polymer framework of water-swollen copolymers of N,N-dimethylacrylamide,
      acrylamido-2-methylpropanesulfonic acid, and ethylenedimethacrylate (nominal
      cross-linking degrees of 4, 8, and 20 mol %) is composed of highly expanded
      domains, with "pores" not less than 6 nm in diameter. When the 4% cross-linked
      copolymer (DAE 26-4) is swollen with a 10(-4) M solution of 4-hydroxy-2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPOL) in water, MeOH, EtOH, or nBuOH, the
      molecules of the paramagnetic probe rotate rapidly (tau<1000 ps) and as fast as
      in the bulk liquid in the case of water. The swelling degree of DAE 26-4 is
      related to the Hansen solubility parameters of a number of liquids, including
      linear alcohols up to n-octanol. It is also found that the rotational correlation
      time of TEMPOL in the copolymer swollen by water and the lightest alcohols
      increases with decreasing specific absorbed volume. Time-domain NMR spectrometry
      of water-swollen DAE 26-4 shows that sorption of only 14% of the liquid required
      for its complete swelling is enough for full hydration of the polymer chains.
      Accordingly, in fully swollen DAE 26-4 the longitudinal relaxation time of water
      closely approaches the value of pure water. {(13)C} CP-MAS NMR on partially and
      fully water swollen samples of DAE 26-4 shows that swelling increases the
      mobility of the polymer chains, as clearly indicated by the narrowing of the best
      resolved peaks. DAE 26-4 was used as an exotemplate for the synthesis of
      nanocomposites composed of the polymer and nanostructured Fe(2)O(3) through a
      series of ion-exchange/precipitation cycles. After the first cycle the
      nanoparticles are 3-4 nm in diameter, with practically unchanged size after
      subsequent cycles (up to five). In fact, the nanoparticle size never exceeded the
      diameter of the largest available pores. This suggests that the polymer framework
      controls the growth of the nanoparticles according to the template-controlled
      synthesis scheme. Selected-area electron diffraction, TEM, and high-resolution
      electron microscopy show that the nanostructured inorganic phase is composed of
      hematite.

PMID- 22461083
TI  - Cloning, expression, and characterization of an alkaline thermostable GH11
      xylanase from Thermobifida halotolerans YIM 90462T.
AB  - A xylanase gene (thxyn11A) from the Thermobifida halotolerans strain YIM 90462(T)
      was cloned and expressed in Escherichia coli. The open reading frame (ORF) of
      thxyn11A has 1,008 bp encoding a mature xylanase with a high degree of similarity
      (80 %) to the xylanase from Nocardiopsis dassonvillei subsp. dassonvillei DSM
      43111. This enzyme (Thxyn11A) also possesses a glycosyl hydrolases family 11
      (GH11) domain and a high isoelectric point (pI = 9.1). However, Thxyn11A varies
      from most GH11 xylanases, due to its large molecular mass (34 kDa). Recombinant
      Thxyn11A demonstrated a strong pH and temperature tolerance with a maximum
      activity at pH 9.0 and 70  degrees C. Xylotriose, the end-product of xylan
      hydrolysis by Thxyn11A, serves as a catalyst for hemicellulose pretreatment in
      industrial applications and can also function as a food source or supplement for
      enterobacteria. Due to its attractive biochemical properties, Thxyn11A may have
      potential value in many commercial applications.

PMID- 22461084
TI  - Childhood separation anxiety disorder and adult onset panic attacks share a
      common genetic diathesis.
AB  - BACKGROUND: Childhood separation anxiety disorder (SAD) is hypothesized to share
      etiologic roots with panic disorder. The aim of this study was to estimate the
      genetic and environmental sources of covariance between childhood SAD and adult
      onset panic attacks (AOPA), with the primary goal to determine whether these two
      phenotypes share a common genetic diathesis. METHODS: Participants included
      parents and their monozygotic or dizygotic twins (n = 1,437 twin pairs)
      participating in the Virginia Twin Study of Adolescent Behavioral Development and
      those twins who later completed the Young Adult Follow-Up (YAFU). The Child and
      Adolescent Psychiatric Assessment was completed at three waves during
      childhood/adolescence followed by the Structured Clinical Interview for DSM-III-R
      at the YAFU. Two separate, bivariate Cholesky models were fit to childhood
      diagnoses of SAD and overanxious disorder (OAD), respectively, and their relation
      with AOPA; a trivariate Cholesky model also examined the collective influence of
      childhood SAD and OAD on AOPA. RESULTS: In the best-fitting bivariate model, the
      covariation between SAD and AOPA was accounted for by genetic and unique
      environmental factors only, with the genetic factor associated with childhood SAD
      explaining significant variance in AOPA. Environmental risk factors were not
      significantly shared between SAD and AOPA. By contrast, the genetic factor
      associated with childhood OAD did not contribute significantly to AOPA. Results
      of the trivariate Cholesky reaffirmed outcomes of bivariate models. CONCLUSIONS:
      These data indicate that childhood SAD and AOPA share a common genetic diathesis
      that is not observed for childhood OAD, strongly supporting the hypothesis of a
      specific genetic etiologic link between the two phenotypes.

PMID- 22461085
TI  - Genome analysis of the new human polyomaviruses.
AB  - Polyomaviridae is a growing family of naked, double-stranded DNA viruses that
      infect birds and mammals. The last few years, several new members infecting birds
      or primates have been discovered, including seven human polyomaviruses: KI, WU,
      Merkel cell polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated
      polyomavirus, and HPyV9. In addition, DNA and antibodies against the monkey
      lymphotropic polyomavirus have been detected in humans, indicating that this
      virus can also infect man. However, little is known about the route of infection,
      transmission, cell tropism, and, with the exception of Merkel cell polyomavirus
      and trichodysplasia spinulosa-associated polyomavirus, the pathogenicity of these
      viruses. This review compares the genomes of these emerging human polyomaviruses
      with previously known polyomaviruses detected in man, reports mutations in
      different isolates, and predicts structural and functional properties of their
      viral proteins.

PMID- 22461086
TI  - Analysis of neurotransmitter distribution in brain development of benthic and
      pelagic octopod cephalopods.
AB  - The database on neurotransmitter distribution during central nervous system
      development of cephalopod mollusks is still scarce. We describe the ontogeny of
      serotonergic (5-HT-ir) and FMRFamide-like immunoreactive (Fa-lir) neurons in the
      central nervous system of the benthic Octopus vulgaris and Fa-lir distribution in
      the pelagic Argonauta hians. Comparing our data to previous studies, we aim at
      revealing shared immunochemical domains among coleoid cephalopods, i.e., all
      cephalopods except nautiluses. During development of O. vulgaris, 5-HT-ir and Fa
      lir elements occur relatively late, namely during stage XII, when the brain
      neuropils are already highly differentiated. In stage XII-XX individuals, Fa-lir
      cell somata are located in the middle and posterior subesophageal mass and in the
      optic, posterior basal, and superior buccal lobes. 5-HT is predominately
      expressed in cell somata of the superior buccal, anterior basal, and optic lobes,
      as well as in the subesophageal mass. The overall population of Fa-lir neurons is
      larger than the one expressing 5-HT. Fa-lir elements are distributed throughout
      homologous brain areas of A. hians and O. vulgaris. We identified neuronal
      subsets with similar cell number and immunochemical phenotype in coleoids. These
      are located in corresponding brain regions of developmental stages and adults of
      O. vulgaris, A. hians, and the decapod squid Idiosepius notoides. O. vulgaris and
      I. notoides exhibit numerous 5-HT-ir cell somata in the superior buccal lobes but
      none or very few in the inferior buccal lobes. The latter have previously been
      homologized to the gastropod buccal ganglia, which also lack 5-HT-ir cell somata
      in euthyneuran gastropods. Among coleoids, 5-HT-ir neuronal subsets, which are
      located ventrally to the lateral anterior basal lobes and in the anterior middle
      subesophageal mass, are candidates for homologous subsets. Contrary to I.
      notoides, octopods exhibit Fa-lir cell somata ventrally to the brachial lobes and
      5-HT-ir cell somata close to the stellate ganglia.

PMID- 22461088
TI  - A new approach towards the asymmetric fluorination of alkenes using anionic phase
      transfer catalysts.

PMID- 22461087
TI  - Chemical stability of amorphous materials: specific and general media effects in
      the role of water in the degradation of freeze-dried zoniporide.
AB  - The objective of the present work was to determine whether hydrolysis in a model
      lyophile was influenced by general media effects with water-changing properties
      of the medium or via a specific mechanism of water as a reactant. Four
      formulations of zoniporide and sucrose (1:10) were prepared with variable amounts
      of sorbitol [0%-25% (w/v) of total solids). These formulations were then
      equilibrated at 6% and 11% relative humidity using saturated salt solutions. The
      lyophile cakes were analyzed by differential scanning calorimetery (DSC),
      (isothermal microcalorimetry (IMC), solid- state nuclear magnetic resonance
      (ssNMR) spectroscopy, and ultraviolet-visible diffuse reflectance (DFR)
      spectroscopy. DSC and IMC were used to assess the global molecular mobility.
      ssNMR relaxation times were measured to access local mobility. The DFR was used
      to determine the solid-state acidity expressed as the Hammett acidity function.
      Stability of samples was evaluated at 40 degrees C by monitoring potency and
      purity by high-performance liquid chromatography (HPLC). Results were interpreted
      in terms of the various roles of water: media effect, plasticization, polarity,
      and reactant. The kinetics of hydrolysis was observed to be correlated with
      either/both specific "chemical" effects, that is, water reactant as well as media
      effect, specifically global molecular mobility of the matrix. Increase in
      reaction rate with increase in water content is not linear and is a weaker
      dependence than in some hydrolytic reactions in organic solvents. A moderate
      amount of an inert plasticizer, sorbitol, conferred additional stabilization,
      possibly by restricting the amplitude and frequency of fast motions that are on a
      small length scale.

PMID- 22461089
TI  - Magnetic nanoparticles for biomedical applications.

PMID- 22461090
TI  - Distribution of P75 neurotrophin receptor in adult human cochlea--an
      immunohistochemical study.
AB  - Mechanisms underlying the unique survival property of human spiral neurons are
      yet to be explored. P75 (p75(NTR)) is a low affinity receptor for neurotrophins
      and is known to interact with Trk receptors to modulate ligand binding and
      signaling. Up-regulation of this receptor was found to be associated with
      apoptosis as well as with cell proliferation. Its distribution and injury-induced
      change in expression pattern in the cochlea have been mainly studied in rodents.
      There is still no report concerning p75(NTR) in post-natal human inner ear. We
      analyzed, for the first time, p75(NTR) expression in five freshly fixed human
      cochleae by using immunohistochemistry techniques, including myelin basic protein
      (MBP) as a myelin sheath marker and TrkB as the human spiral neuron marker, and
      by using thin optical sectioning of laser confocal microscopy. The inner ear
      specimens were obtained from adult patients who had normal pure tone thresholds
      before the surgical procedures, via a trans-cochlear approach for removal of
      giant posterior cranial fossa meningioma. The expression of p75(NTR) was
      investigated and localized in the glial cells, including Schwann cells and
      satellite glial cells in the Rosenthal canal, in the central nerve bundles within
      the modiolus, and in the osseous spiral lamina of the human cochleae. The
      biological significance of p75(NTR) in human cochlea is discussed.

PMID- 22461091
TI  - From the Editor-in-Chief.

PMID- 22461092
TI  - The role of pharmacogenetics and pharmacogenomics in improving translational
      medicine.
AB  - The approval of new medicines has slowed significantly over the past years. In
      order to accelerate the development of new compounds, novel approaches in drug
      development are required. Translational medicine or research, an emerging
      discipline on the frontier of basic science and medical practice, has the
      potential to enhance the speed and efficiency of the drug development process
      through the utilization of pharmacogenetics and pharmacogenomics.
      Pharmacogenetics is the study of genetic causes of individual variations in drug
      response whereas pharmacogenomics deals with the simultaneous impact of multiple
      mutations in the genome that may determine the patient's response to drug
      therapy. The utilization of these methods in the drug development process may
      therefore identify patient sub-populations that exhibit more effective responses
      and/or an improved benefit/risk profile upon treatment. The authors provide
      examples of the use of pharmacogenetics and pharmacogenomics in the fields of
      cardiovascular, pulmonary, oncological, and bone diseases and also highlight the
      potential economic value of their development.

PMID- 22461094
TI  - Transforming the practice of medicine using genomics.
AB  - Recent studies have demonstrated the use of genomic data, particularly gene
      expression signatures, as clinical prognostic factors in complex diseases. Such
      studies herald the future for genomic medicine and the opportunity for
      personalized prognosis in a variety of clinical contexts that utilize genomescale
      molecular information. Several key areas represent logical and critical next
      steps in the use of complex genomic profiling data towards the goal of
      personalized medicine. First, analyses should be geared toward the development of
      molecular profiles that predict future events - such as major clinical events or
      the response, resistance, or adverse reaction to therapy. Secondly, these must
      move into actual clinical practice by forming the basis for the next generation
      of clinical trials that will employ these methodologies to stratify patients.
      Lastly, there remain formidable challenges is in the translation of genomic
      technologies into clinical medicine that will need to be addressed: professional
      and public education, health outcomes research, reimbursement, regulatory
      oversight and privacy protection.

PMID- 22461095
TI  - Role of regulatory agencies in translating pharmacogenetics to the clinics.
AB  - Overall, the regulators (here the term is used in the broad sense including
      competent authorities, the national departments of health and the European
      commission) have a significant role in translating pharmacogenomics into clinical
      practice. The first objective is to establish the role of the genomic information
      that is available, and this should be data driven. Conduct of robust clinical
      trials that are sound both scientifically and from a regulatory perspective
      should be encouraged. Significant interaction between Academia, Pharma industry
      and the regulator is essential with the overall aim of improving public health.
      Conceptually, this would involve the triumvirate (Academia, industry and
      regulators) as an orchestra with the regulators perhaps taking the role of the
      conductor while the significant players would be those that generate data
      (Academia and industry). The regulators also need to ensure that clear guidance
      is available for use of the information and the tests with a significant level of
      uniformity between the ICH regions. The commercial availability of the test will
      have considerable impact on the use of pharmacogenomics, but this is currently
      beyond the scope of this paper.

PMID- 22461096
TI  - The latest news from the GENOMOS study.
AB  - Most common age-related diseases such as osteoporosis, have strong genetic
      influences and therefore intense efforts are ongoing to identify the underlying
      genetic variants. Knowledge of these variants can help in understanding the
      disease process and might benefit development of interventions and diagnostics.
      Association studies have now become the standard approach to uncover the genetic
      effects of common variants. Yet, in all fields of complex disease genetics -
      including osteoporosis - progress in identifying these genetic factors has been
      hampered by often controversial results. Because of the complicated genetic
      architecture of the diseases and the small effect size for each individual risk
      alleles, this is mostly due to low statistical power and limitations of
      analytical methods. It is now recognised that association analysis followed by
      replication and prospective multi-centred meta-analysis is currently the best way
      forward to identify genetic markers for complex traits, such as osteoporosis. To
      accomplish this, large (global) collaborative consortia have been established
      that have large collections of DNA samples from subjects with a certain phenotype
      and that use standardized methodology and definitions, to quantify by meta
      analysis the subtle effects of the responsible gene variants. The GENOMOS
      consortium has played such a role in the field of osteoporosis and has initially
      identified and refuted associations of well known candidate genes. This
      consortium is now expected to play an important role in validation of risk
      alleles coming from Genome Wide Association Studies (GWAS) for osteoporosis, some
      of which have just been published. Together with genetic studies on more rare
      syndromes, the GWA approach in combination with the GENOMOS consortium, is likely
      to help in clarifying the genetic architecture of complex bone traits such as
      BMD, and - eventually - in understanding the genetics of clinically relevant
      endpoints in osteoporosis, i.e., fracture risk. Such genetic insights will be
      useful in understanding biology and are likely to also find applications in
      clinical practice.

PMID- 22461093
TI  - Pharmacogenetics: implementing personalized medicine.
AB  - Pharmacogenetics and pharmacogenomics have been widely recognized as fundamental
      steps toward personalized medicine. They deal with genetically determined
      variants in how individuals respond to drugs, and hold the promise to
      revolutionize drug therapy by tailoring it according to individual genotypes.The
      clinical need for novel approaches to improve drug therapy derives from the high
      rate of adverse reactions to drugs and their lack of efficacy in many individuals
      that may be predicted by pharmacogenetic testing.Significant advances in
      pharmacogenetic research have been made since inherited differences in response
      to drugs such as isoniazid and succinylcholine were explored in the 1950s. The
      clinical utility and applications of pharmacogenetics and pharmacogenomics are at
      present particularly evident in some therapeutic areas (anticancer, psycotrophic,
      and anticoagulant drugs).Recent evidence derived from several studies includes
      screening for thiopurine methyl transferase or uridine 5'-diphosphoglucuronosyl
      transferase 1A1 gene polymorphisms to prevent mercaptopurine and azathioprine or
      irinotecan induced myelosuppression, respectively. Also there is a large body of
      information concerning cytochrome P450 gene polymorphisms and their relationship
      to drug toxicity and response. Further examples include screening the presence of
      the HLA-B*5701 allele to prevent the hypersensitivity reactions to abacavir and
      the assessment of the human epidermal growth factor receptor (HER-2) expression
      for trastuzumab therapy of breast cancer or that of KRAS mutation status for
      cetuximab or panitumumab therapy in colorectal cancer.Moreover, the application
      of pharmacogenetics and pharmacogenomics to therapies used in the treatment of
      osteoarticular diseases (e.g. rheumatoid arthritis, osteoporosis) holds great
      promise for tailoring therapy with clinically relevant drugs (e.g. disease
      modifying antirheumatic drugs, vitamin D, and estrogens). Although the classical
      candidate gene approach has helped unravel genetic variants that influence
      clinical drug responsiveness, gene-wide association studies have recently gained
      attention as they enable to associate specific genetic variants or quantitative
      differences in gene expression with drug response.Although research findings are
      accumulating, most of the potential of pharmacogenetics and pharmacogenomics
      remains to be explored and must be validated in prospective randomized clinical
      trials.The genetic and molecular foundations of personalized medicine appear
      solid and evidence indicates its growing importance in healthcare.

PMID- 22461097
TI  - The genetics of response to estrogen treatment.
AB  - It has been demonstrated that the response to estrogen treatment in
      postmenopausal women shows considerable variability. It has been speculated that
      this at least partly could be determined by heritable factors.The most obvious
      genes to investigate in this context are the estrogen receptor genes. It has been
      demonstrated that women with short alleles of the TA-repeat polymorphism in the
      estrogen receptor alpha gene respond to hormone treatment with greater increases
      in bone mass at the lumbar spine. Also the two polymorphisms in the first intron
      of the same gene have been found to be associated with the response to estrogen.
      Several studies have found that women carrying the Pand the X-alleles respond to
      hormone therapy with greater increases in bone mass and sustain fewer fractures.
      Polymorphisms in the collagen type Ialpha1 have been found to influence BMD.
      Conflicting results have been obtained with respect to the influence of these
      genetic variants on postmenopausal bone loss and response to hormone treatment.
      Furthermore, two polymorphisms in the promoter of the transforming growth factor
      beta gene and one polymorphism in the first exon of the osteoprotegerin gene have
      been demonstrated to interact with the response to hormone treatment in early
      postmenopausal women.The above mentioned results are obtained from relatively
      small studies and needs confirmation before the information can be used in the
      clinic.

PMID- 22461098
TI  - Genetics of the bone response to bisphosphonate treatments.
AB  - Bone mineral density (BMD) is the best established marker for bone health. Over
      the last years a large number of studies have pointed to the variability in many
      target genes and their relation with bone mass and with other determinants of
      fracture risk such as ultrasound bone properties, skeletal geometry and bone
      turnover markers. The importance of genetic factors in the bone quality is
      substantial, but no consensus exists yet on the genes that are involved.
      Furthermore, there are many differences of clinical outcomes during bone-active
      treatments in the population-based studies. Heterogeneity in drug response may
      reflect varying responsiveness to boneactive treatments due to allele variation
      in the polymorphic target genes. In this regard, polymorphisms of vitamin D
      receptor and estrogen receptor loci appear genetic determinants of their
      corresponding hormonal treatment response such as vitamin D and estrogens. The
      present review focuses on the genetic determinants involved in the clinical
      response to bisphosphonate treatments for bone disorders. Knowledge of the
      molecular and functional consequences of the target genes is crucial to fully
      appreciate their significance and understand their potential clinical
      implications.

PMID- 22461100
TI  - Systemic mastocytosis with skeletal involvement: a case report and review of the
      literature.
AB  - Systemic Mastocytosis (SM) comprises a heterogeneous group of disorders of mast
      cell proliferation. Infiltration, including skin and bone, of multiple mast cells
      may occur as cutaneous and systemic variants. A rare form of osteoporosis has
      been also described as expression of the skeletal involvement. Here, we describe
      a case of a 57-years-old woman with SM and, according to the clinical diagnosis,
      evaluate the possible mechanism underlying osteoporosis. Moreover, a review of
      the literature, particularly regarding the use of bisphosphonates in this rare
      disease is also presented.

PMID- 22461099
TI  - Pharmacogenetics of cardiovascular drug therapy.
AB  - In developed countries cardiovascular disease is one of the leading causes of
      death. Cardiovascular drugs such as platelet aggregation inhibitors, oral
      anticoagulants, antihypertensives and cholesterol lowering drugs are abundantly
      prescribed to reduce risk of cardiovascular disease. Notable interindividual
      variation exists in the response to these pharmacotherapeutic interventions,
      which can be partially explained by factors such as gender, age, diet,
      concomitant drug use and environmental factors. Notwithstanding, a great part of
      this variability remains unknown. To a smaller or larger extent, genetic
      variability may contribute to the variability in response to these cardiovascular
      drugs. This review gives an overview of pharmacogenetic studies of genes that
      were reported to be associated with four commonly prescribed drugs/drug classes
      (platelet aggregation inhibitors, coumarins, antihypertensives and statins) and
      were studied at least 2 times with a similar outcome measure. In the field of
      cardiovascular drug therapy, polymorphisms in candidate genes such as the
      cycloxygenase-1, vitamin K reductase complex subunit 1, CYP2C9, alpha adducin and
      3-hydroxy-3-methylglutaryl-CoA reductase have received a great amount of interest
      in the pharmacogenetics of aspirin, coumarins, antihypertensives and statins
      respectively. However, only variations in VKORC1 and CYP2C9 have consistently
      been associated with drug response (coumarins) and have clinical implications.
      Clinical trials should provide evidence for the effectiveness of genotyping
      before this procedure will be a part of every day anticoagulant therapy. In spite
      of the tremendous amount of publications in this field, there is no reason to
      advocate for genetic testing for any other drugs cardiovascular drug therapy yet.
      Current approaches in pharmacogenetic research do not seem to lead to results
      that meet our expectations of individualized medicine. Therefore, new approaches
      are needed addressing issues and challenges such as the number of SNPs studied,
      study power, study design and application of new statistical methods in (pharmaco
      )genetic analysis.

PMID- 22461101
TI  - Nutrient intake and risk of open-angle glaucoma: the Rotterdam Study.
AB  - Open-angle glaucoma (OAG) is the commonest cause of irreversible blindness
      worldwide. Apart from an increased intraocular pressure (IOP), oxidative stress
      and an impaired ocular blood flow are supposed to contribute to OAG. The aim of
      this study was to determine whether the dietary intake of nutrients that either
      have anti-oxidative properties (carotenoids, vitamins, and flavonoids) or
      influence the blood flow (omega fatty acids and magnesium) is associated with
      incident OAG. We investigated this in a prospective population-based cohort, the
      Rotterdam Study. A total of 3502 participants aged 55 years and older for whom
      dietary data at baseline and ophthalmic data at baseline and follow-up were
      available and who did not have OAG at baseline were included. The ophthalmic
      examinations comprised measurements of the IOP and perimetry; dietary intake of
      nutrients was assessed by validated questionnaires and adjusted for energy
      intake. Cox proportional hazard regression analysis was applied to calculate
      hazard ratios of associations between the baseline intake of nutrients and
      incident OAG, adjusted for age, gender, IOP, IOP-lowering treatment, and body
      mass index. During an average follow-up of 9.7 years, 91 participants (2.6%)
      developed OAG. The hazard ratio for retinol equivalents (highest versus lowest
      tertile) was 0.45 (95% confidence interval 0.23-0.90), for vitamin B1 0.50 (0.25
      0.98), and for magnesium 2.25 (1.16-4.38). The effects were stronger after the
      exclusion of participants taking supplements. Hence, a low intake of retinol
      equivalents and vitamin B1 (in line with hypothesis) and a high intake of
      magnesium (less unambiguous to interpret) appear to be associated with an
      increased risk of OAG.

PMID- 22461102
TI  - The mendosal suture.

PMID- 22461103
TI  - The interindividual variation in femoral neck width is associated with the
      acquisition of predictable sets of morphological and tissue-quality traits and
      differential bone loss patterns.
AB  - A better understanding of femoral neck structure and age-related bone loss will
      benefit research aimed at reducing fracture risk. We used the natural variation
      in robustness (bone width relative to length) to analyze how adaptive processes
      covary traits in association with robustness, and whether the variation in
      robustness affects age-related bone loss patterns. Femoral necks from 49 female
      cadavers (29-93 years of age) were evaluated for morphological and tissue-level
      traits using radiography, peripheral quantitative computed tomography, micro
      computed tomography, and ash-content analysis. Femoral neck robustness was
      normally distributed and varied widely with a coefficient of variation of 14.9%.
      Age-adjusted partial regression analysis revealed significant negative
      correlations (p < 0.05) between robustness and relative cortical area, cortical
      tissue-mineral density (Ct.TMD), and trabecular bone mineral density (Ma.BMD).
      Path analysis confirmed these results showing that a one standard deviation (SD)
      increase in robustness was associated with a 0.70 SD decrease in RCA, 0.47 SD
      decrease in Ct.TMD, and 0.43 SD decrease in Ma.BMD. Significantly different bone
      loss patterns were observed when comparing the most slender and most robust
      tertiles. Robust femora showed significant negative correlations with age for
      cortical area (R(2) = 0.29, p < 0.03), Ma.BMD (R(2) = 0.34, p < 0.01), and Ct.TMD
      (R(2) = 0.4, p < 0.003). However, slender femora did not show these age-related
      changes (R(2) < 0.09, p > 0.2). The results indicated that slender femora were
      constructed with a different set of traits compared to robust femora, and that
      the natural variation in robustness was a determinant of age-related bone loss
      patterns. Clinical diagnoses and treatments may benefit from a better
      understanding of these robustness-specific structural and aging patterns.

PMID- 22461105
TI  - PPARalpha agonists--an emerging concept in the management of neuropathic and
      visceral pain.

PMID- 22461104
TI  - The effect of intermittent alcohol vapor or pulsatile heroin on somatic and
      negative affective indices during spontaneous withdrawal in Wistar rats.
AB  - RATIONALE: Once dependent on alcohol or opioids, negative affect may accompany
      withdrawal. Dependent individuals are hypothesized to "self-medicate" in order to
      cope with withdrawal, which promotes escalated alcohol and drug use. OBJECTIVES:
      The current study aimed to develop a reliable animal model to assess symptoms
      that occur during spontaneous alcohol and opioid withdrawal. METHODS: Dependence
      was induced using intermittent alcohol exposure or pulsatile heroin delivery and
      assessed for the presence of withdrawal symptoms during acute withdrawal by
      measuring somatic signs, behavior in the forced swim test (FST), and air-puff
      induced 22-kHz ultrasonic vocalizations (USVs). Additional animals subjected to 8
      weeks of alcohol vapor exposure were evaluated for altered somatic signs, operant
      alcohol self-administration, and 22-kHz USV production, as well as performance in
      the elevated plus maze (EPM). RESULTS: During spontaneous withdrawal from
      pulsatile heroin or intermittent alcohol vapor, animals displayed increased
      somatic withdrawal signs, FST immobility, and 22-kHz USV production but did not
      show any behavioral change in the EPM unless the duration of alcohol exposure was
      extended to 4 weeks. Following 8 weeks of alcohol vapor exposure, animals
      displayed somatic withdrawal signs, escalated alcohol self-administration, and
      increased 22-kHz USVs. CONCLUSIONS: These paradigms provide consistent methods to
      evaluate the behavioral ramifications, and neurobiological substrates, of alcohol
      and opioid dependence during spontaneous withdrawal. As immobility in the FST and
      percent open-arm time in the EPM were dissociable, with 22-kHz USVs paralleling
      immobility in the FST, assessment of air-puff-induced 22-kHz USVs could provide
      an ethologically valid alternative to the FST.

PMID- 22461106
TI  - Expression of high mobility group A2 is associated with poor survival in
      hepatocellular carcinoma.

PMID- 22461107
TI  - Chlorine-induced assembly of a cationic coordination cage with a MU5-carbonato
      bridged Mn(II)24 core.
AB  - Chlorine caged in! The chlorine-induced assembly of six shuttlecock-like
      tetranuclear Mn(II) building blocks generated in situ based on p-tert
      butylthiacalix[4]arene and facial anions gave rise to a novel truncated distorted
      octahedral cationic coordination cage with a MU(5)-carbonato-bridged Mn(II)(24)
      core.

PMID- 22461108
TI  - Laparoscopic splenectomy and esophagogastric devascularization is a safe,
      effective, minimally invasive alternative for the treatment of portal
      hypertension with refractory variceal bleeding.
AB  - Open splenectomy and esophagogastric devascularization (OSED) is a typical
      surgery for portal hypertension. Because of the high morbidity associated with
      it, it is desirable to develop a minimally invasive alternative. To investigate
      the safety and effect of laparoscopic splenectomy and esophagogastric
      devascularization (LSED), we performed LSED for 24 patients suffering from portal
      hypertension with refractory variceal bleeding while conducting OSED for 30
      patients. The perioperative data and follow-up results were analyzed. Operation
      times were similar in both groups. Less intraoperative blood and faster return of
      gastrointestinal function were found in the LSED group. The LSED group had lower
      levels of alanine aminotransferase, aspartate aminotransferase, and total
      bilirubin after surgery. In both groups, the levels of platelet count, white
      blood cell count, or hemoglobin were increased after operation dramatically.
      During the follow-up period (range = 3-36 months), no patient had recurrent
      hypersplenism or variceal bleeding. Hence, LSED is a safe and minimally invasive
      intervention for portal hypertension with refractory variceal bleeding.

PMID- 22461109
TI  - Structural transformation with "negative volume expansion": chemical bonding and
      physical behavior of TiGePt.
AB  - The synthesis and a joint experimental and theoretical study of the crystal
      structure and physical properties of the new ternary intermetallic compound
      TiGePt are presented. Upon heating, TiGePt exhibits an unusual structural phase
      transition with a huge volume contraction of about 10 %. The transformation is
      characterized by a strong change in the physical properties, in particular, by an
      insulator-metal transition. At temperatures below 885  degrees C TiGePt
      crystallizes in the cubic MgAgAs (half-Heusler) type (LT phase, space group F43m,
      a = 5.9349(2) A). At elevated temperatures, the crystal structure of TiGePt
      transforms into the TiNiSi structure type (HT phase, space group Pnma, a =
      6.38134(9) A, b = 3.89081(5) A, c = 7.5034(1) A). The reversible, temperature
      dependent structural transition was investigated by in-situ neutron powder
      diffraction and dilatometry measurements. The insulator-metal transition,
      indicated by resistivity measurements, is in accord with band structure
      calculations yielding a gap of about 0.9 eV for the LT phase and a metallic HT
      phase. Detailed analysis of the chemical bonding in both modifications revealed
      an essential change of the Ti-Pt and Ti-Ge interactions as the origin of the
      dramatic changes in the physical properties.

PMID- 22461110
TI  - High-resolution subunit detection of glutamate receptor by ultrasmall gold
      nanoparticles.
AB  - In this study, we aimed to increase the sensitivity of protein labeling using 1.4
      nm gold nanoparticles and glutamate delta2 receptor (GluD2) from the postsynaptic
      membrane of the Purkinje cells. The very small marker size of the particles
      reduces the steric hindrance between antibodies leading to a higher labeling
      efficiency of more than one subunit per single receptor molecule. The
      nanoparticles are visible in 200 kV dark-field scanning transmission electron
      microscope on freeze-fractured carbon replica of nervous tissue after plasma
      cleaning treatment. The different elemental composition of nanoparticles as Au
      nanogold or CdS quantum dot can be distinguished by energy dispersive X-ray
      spectroscopy. This method ensures detection of an average of three subunits per
      GluD2 and often labels all four of them with 1.4 nm Au nanoparticles. It is
      concluded that this high-resolution microscopic method is useful for exploring
      the quaternary structure of membrane proteins.

PMID- 22461111
TI  - Importance of monocyte deactivation in determining early outcome after
      ventricular assist device implantation.
AB  - BACKGROUND: Patients undergoing mechanical circulatory support using ventricular
      assist devices (VADs) experience a postoperative mixed antagonistic
      (proinflammatory and antiinflammatory) response syndrome. This response can
      result in immunoparalysis, exposing VAD recipients to infection and interfering
      with patient recovery despite adequate hemodynamic support. We undertook the
      present study to evaluate whether postoperative monocytic human leukocyte antigen
      DR (mHLA-DR) expression is of prognostic value for mortality or infection of VAD
      recipients during their initial intensive care unit (ICU) stay after
      implantation. METHODS: Since 2004, we have monitored postoperative mHLA-DR
      expression in 50 VAD recipients using flow cytometry. RESULTS: Thirty-seven
      patients (74%) developed infection, and 22 patients (44%) died during their
      initial ICU stay. mHLA-DR expression was lowest in the immediate postoperative
      period (postoperative days [PODs] 1-3) but increased progressively thereafter.
      Multiple regression analysis showed that preoperative aspartate aminotransferase
      level was the only significant and independent predictor of the percentage of HLA
      DR-positive monocytes on PODs 1-3 (beta = -0.726, p = 0.0001). ICU death and
      infection were associated with significantly lower percentages of HLA-DR-positive
      monocytes on PODs 1-3. ROC curve analysis revealed that the percentage of HLA-DR
      positive monocytes on PODs 1-3 had significant discriminative power for ICU death
      (area under the curve = 0.73, 95% confidence interval, 0.545-0.912, p = 0.037),
      but not for infection. CONCLUSIONS: Postoperative mHLA-DR expression was closely
      related to preoperative hepatic cytolysis. It appeared to be the only early
      postoperative biological parameter that had some predictive power for death of
      VAD recipients in the ICU.

PMID- 22461112
TI  - Assessment of the heart failure pharmacotherapy of patients with continuous flow
      left-ventricular assist devices.
AB  - PURPOSE: The purpose of this project was to characterize the use of heart failure
      medications during the first year after left-ventricular assist device (LVAD)
      implantation. METHODS: All patients who received a HeartMate II at our
      institution between January 1, 2007, and August 1, 2009, and were followed by our
      multidisciplinary team for at least 6 months were eligible for inclusion. Use of
      heart failure medications, including dosages, was collected for each patient
      prior to LVAD implantation, at time of discharge, and at each subsequent monthly
      office visit for up to 1 year after implantation. The primary end point was the
      prescription rate for each medication class at discharge. Secondary end points
      included the use and dosage of these agents during follow up. RESULTS: A total of
      28 patients were included (mean age = 50+/-11.5 years; sex 75% male; race 57.1%
      white; bridge-to-transplant rate 25%). There was a statistically significant
      decrease in use of digoxin (42.9% vs. 7.1%), spironolactone (50% vs. 17.9%),
      nitrates (39.3% vs. 7.1%), and milrinone (71.4% vs. 3.6%) postimplantation
      compared with baseline (p<0.05, for all comparisons). More than 50% of patients
      received vasodilators, beta-blockers, and hydralazine both preimplantation and
      postimplantation (p>0.05 for each class). Furthermore, more patients reached
      target doses of beta-blockers (0% vs. 28.6%; p=0.04) after LVAD implantation.
      CONCLUSION: Our pilot study shows consistent prescription of heart failure
      pharmacotherapy in LVAD patients at our institution, with more patients able to
      tolerate target doses of beta-blockers.

PMID- 22461113
TI  - In a porcine model of mixed acidemia HES 130/0.4 may support more stable
      hemodynamics during CVVH when compared to gelatine.
AB  - PURPOSE: Continuous veno-venous hemofiltration (CVVH) and mixed acidemia often
      occur simultaneously in critically ill patients. In a previous study in non
      acidemic pigs we found that colloids and CVVH interact specifically with respect
      to hemodynamic stability, with favorable effects for 6% HES 130/0.4 versus 4%
      gelatine (GEL) infusion. In a porcine model, we investigated whether these
      colloid-type associated differences are still dominant under acidemic conditions.
      METHODS: We utilized 5 groups, a non-acidemic reference group receiving HES130
      and CVVH; two acidemic groups receiving HES130 infusion (one with and one without
      CVVH); and two acidemic groups receiving GEL infusion (one with and one without
      CVVH). Mixed acidemia (pH ~7.20) was established by low tidal volume ventilation
      and acid infusion. Stable acidemia/CVVH application was maintained for 3 hours.
      Hemodynamics and blood gases were recorded. RESULTS: Mixed acidemia led to a
      significant decrease in MAP and increase in MPAP in all groups. CVVH led to a
      further decrease in MAP but improved MPAP. During CVVH, HES130 ensured
      significantly higher MAP, Hb, and DO2 values than GEL infusion. In the groups
      without CVVH these differences between HES 130/0.4 and GEL were not observed.
      CONCLUSIONS: As in a previous study in non-acidemic pigs, we found a colloid
      specific influence of HES130 versus GEL on hemodynamics during CVVH under
      acidemia. Again, HES130 infusion may lead to favorable effects. In contrast,
      acidemia without CVVH application was dominant over the impact of a respective
      colloid. The application of a CVVH seems to be an important trigger for the
      overall circulatory response to a particular colloid.

PMID- 22461114
TI  - A novel device for the automatic decellularization of biological tissues.
AB  - OBJECTIVES: Decellularized biological scaffolds represent a promising solution
      for tissue engineering. They offer a good substrate for cells in terms of
      biochemical composition, ultrastructure and mechanical properties without
      generating an immunogenic response. The aim of this study was to design and
      develop a device for the automatic decellularization of biological tissues to
      overcome manual operation limits, toward a good manufacturing practice-compliant
      process. METHODS: A versatile, modular and easy-to-use device was designed, able
      to automatically exchange decellularization fluids and to provide mechanical
      shaking according to a user-defined protocol. Preliminary decellularization tests
      were made on porcine abdominal aortas comparing results between conventional
      process and device-operated process using water, sodium deoxycholate and DNase.
      Vessels were processed up to 4 cycles of the protocol and after each
      decellularization cycle histological analyses (hematoxylin-eosin, Movat
      pentachrome and DAPI stainings) were observed. Preliminary mechanical tests were
      also performed to compare the mechanical behavior of blood vessels processed with
      the 2 methods mentioned above. RESULTS: Briefly, the device consists of
      decellularization chambers, a shaking system and hydraulic modules for the
      exchange of fluids. The device was bench-tested for functionality and reliability
      with positive outcomes. The protocol used revealed to be effective, with a
      progressive tissue decellularization through repeated cycles. No difference
      between manual and automated operation was observed in histological or mechanical
      analyses. CONCLUSIONS: The developed device is able to automate the
      decellularization process lowering operator-related risks, and is a reliable and
      functional tool for clinical use.

PMID- 22461115
TI  - Comparative role of PET and Kt/V determination in pediatric chronic peritoneal
      dialysis.
AB  - INTRODUCTION: Nutritional state and growth are considered as prognostic markers
      of chronic peritoneal dialysis (PD) adequacy in pediatric patients. The
      euvolemia, blood pressure control, and metabolic and electrolytic equilibrium are
      parameters to be achieved by PD treatment. OBJECTIVE: To describe the chronic PD
      prescription parameters of a cohort of pediatric patients and to compare the
      obtained hemodynamic, antrophometric and adequacy results with those suggested by
      the literature. METHODS: Retrospective analysis based on clinical records
      evaluation of 30 pediatric patients undergoing PD for more than 6 months from
      January 1998 to May 2005. RESULTS: In the present study, 17/30 (56.7%) were boys.
      Chronic kidney disease was secondary to uropathy in 66.7% of the cases. The
      infusion volume was > 1,000 ml/m2 in 9 patients. The peritoneal membrane was
      characterized as high (27.8%), high-average (33.3%), low-average (22.2%) and low
      transporter (16.7%). The weekly urea Kt/V was > 2.1 in all the evaluated
      patients. Blood pressure parameters above the 95th percentile despite the use of
      antihypertensive medication were observed in 5/30 patients, four of whom with CKD
      secondary to glomerulopathy. The initial and final Body Mass Index and weight for
      height ratio were preserved in 83.3% (25/30) patients. CONCLUSION: Elevated
      indexes of small solutes removal are easily attained in pediatric PD patients and
      do not imply optimal clinical management do not imply optimal climanagement.

PMID- 22461116
TI  - Application of hybrid blood purification treatment for severe acute arsine
      poisoning.
AB  - OBJECTIVE: Severe acute arsine poisoning (SAAP) complicated by multiple organ
      dysfunction syndrome is a critical clinical illness. The limited efficacy of
      conventional drug therapy prompted us to investigate the application of hybrid
      blood purification treatment (HBPT) to improve the prognosis in critically ill
      patients. The present manuscript describes a series of cases treated with HBPT.
      METHODS: Eleven SAAP subjects were enrolled. The study did not include a control
      group, because of ethical issues. On the basis of conventional therapy, HBPT
      (plasma exchange [PE] + continuous venovenous hemofiltration [CVVH]) was used to
      treat SAAP. PE was performed once a day for 5 days, and CVVH was performed after
      each session of PE for 7 days or more; HBPT treatment duration amounted to an
      average of 10 days (range 7-18 days). Arsenic was detected in blood and discarded
      liquid. Clinical indicators, laboratory parameters, and prognostic indicators
      were assessed. RESULTS: HBPT was smoothly implemented without obvious adverse
      reaction. It can continuously remove arsenic and terminate hemolysis in a time
      dependent manner. HBPT also significantly improved the poor clinical
      manifestations and laboratory indicators of SAAP, leading to a low mortality. Ten
      patients were discharged because of improved conditions, and only 1 patient died.
      CONCLUSIONS: The early application of HBPT can improve the prognosis of SAAP. The
      advantage of HBPT is that it can integrate the characteristics of different blood
      purification technologies to maximize treatment efficacy.

PMID- 22461117
TI  - Influence of ethnicity on health-related quality of life of hemodialysis patients
      in Singapore.
AB  - OBJECTIVES: The association between health-related quality of life (HRQoL) and
      ethnicity has been studied among hemodialysis (HD) patients in several countries
      with varying results. However, the effect of ethnicity on the HRQoL of HD
      patients in the Asian context has yet to be evaluated. This study seeks to
      examine the HRQoL of HD patients in Singapore and to understand the influence of
      ethnicity on their HRQoL. METHODS: A census-style survey inclusive of the KDQoL
      SF. The AMA was conducted among all HD patients from 22 dialysis centers across
      Singapore. Multiple linear regression models were used to analyze the influence
      of ethnicity on each SF-36 scale while adjusting for the influence of
      socioeconomic status (SES) factors and other determinants of HRQoL. RESULTS: Data
      from 1,249 HD patients were analyzed. Response rate was 63.3%. Compared with
      other ethnicities, Chinese were most likely to report lower HRQoL. After
      adjusting for sex, age, and other possible determinants of HRQoL, the influence
      of ethnicity on HRQoL persisted, with significant mean differences in role
      physical, general health, role-emotional, and physical component summary scales.
      CONCLUSIONS: After adjusting for demographic, SES, and other factors, ethnicity
      remained an important factor influencing HRQoL of Singaporean HD patients.
      Further studies are needed to identify modifiable factors that might explain the
      interethnic differences in HRQoL among HD patients.

PMID- 22461118
TI  - Oxidative stress markers in hemodialysis and peritoneal dialysis patients,
      including coenzyme Q10 and ischemia-modified albumin.
AB  - OBJECTIVES: Oxidative stress results from an imbalance between the production of
      free radicals and antioxidant activity. There is wide agreement that patients
      undergoing regular dialysis treatment experience increased oxidative stress. The
      aim of this study was to investigate serum total antioxidant status (TAS), total
      oxidant status (TOS), ischemia-modified albumin (IMA), and coenzyme Q10 (CoQ10)
      levels in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD)
      patients, compared with controls. METHODS: This study was performed on 41 (21
      men, 20 women) CAPD patients, 38 (20 men,18 women) HD patients, and 43 (23 men,
      20 women) healthy control subjects. CoQ10 levels were standardized using blood
      lipids. RESULTS: Serum TAS levels and CoQ10/total cholesterol values of the HD
      and CAPD patients were significantly lower, whereas serum IMA and TOS levels were
      significantly higher, than those of controls. Furthermore, CoQ10/LDL,
      CoQ10/triglycerides, and CoQ10/total cholesterol + triglycerides values of the
      CAPD patients were significantly lower than those of controls. No differences
      were found between serum IMA, TAS, TOS, CoQ10 levels, and adjusted CoQ10 values
      of the CAPD and HD patients. CONCLUSIONS: Our results suggest that oxidative
      stress is increased in HD and CAPD patients compared with controls, as proven by
      decreased TAS and adjusted CoQ10 levels and increased TOS and IMA levels.
      Therefore, an antioxidant supplementation to these patients may be suggested.

PMID- 22461119
TI  - Cost is not a barrier to implementing clopidogrel pharmacogenetics.

PMID- 22461120
TI  - Recommendations for generating, evaluating, and implementing drug-drug
      interaction evidence.
AB  - In October 2009, a 2-day, multistakeholder, national conference was held in
      Rockville, Maryland, to discuss and propose methods to improve the drug-drug
      interaction (DDI) evidence base and its evaluation and integration into clinical
      decision support (CDS) systems. The conference featured participants representing
      consumers, health care providers, those responsible for relevant policies and
      guidelines, and developers and vendors of DDI compendia, databases, and CDS
      systems. One desired outcome of the conference was to prepare recommendations on
      critical issues surrounding DDI evidence. A set of recommendations was developed
      to improve the generation, evaluation, and translation of DDI evidence into CDS
      systems based on presentations by experts and the supporting literature. These
      recommendations were reviewed initially by conference moderators, speakers, and
      Scientific Steering and Planning Committee members, and subsequently by all
      attendees. The following recommendations were developed to increase patient
      safety by improving the relevance and assessment of DDI evidence: conduct well
      designed studies to determine the incidence, outcomes, and patient-level risk
      factors for DDIs; use a systematic and transparent process for evaluating the DDI
      evidence in order to estimate the severity and risks of DDIs; and improve the
      integration of DDI evidence into electronic CDS. Opportunities exist to improve
      the DDI evidence base, develop and promote a systematic approach for evaluating
      the evidence, and integrate this evidence into meaningful CDS.

PMID- 22461121
TI  - Efficacy and safety of innovator versus generic drugs in patients with epilepsy:
      a systematic review.
AB  - Generic antiepileptic drugs achieve blood concentrations similar to those of
      innovator drugs in healthy volunteers, but their comparative effectiveness has
      not been well evaluated. Thus, we assessed the efficacy, tolerability, and safety
      of innovator versus generic antiepileptic drugs. We searched the MEDLINE
      database, Cochrane Central Register of Controlled Trials, Cochrane Database of
      Systematic Reviews, and Web of Science for studies that evaluated innovator and
      generic antiepileptic drugs in patients with epilepsy and reported data on
      prespecified outcomes. We extracted data on study design, interventions, quality
      criteria, study population, baseline characteristics, and outcomes. Compared with
      initiation of innovator antiepileptic drugs, initiation of generic antiepileptic
      drugs did not significantly alter seizure occurrence (relative risk [RR] 0.87,
      95% confidence interval [CI] 0.64-1.18; strength of evidence: low) or frequency
      (standardized mean difference 0.03, 95% CI -0.08-0.14; strength of evidence:
      low), withdrawals due to lack of efficacy (RR 1.02, 95% CI 0.41-2.54; strength of
      evidence: low) or adverse events (RR 0.79, 95% CI 0.28-2.20; strength of
      evidence: low), pharmacokinetic concentrations (maximum, minimum, or area under
      the curve [strength of evidence: low]), or a myriad of adverse events (strength
      of evidence: low or insufficient) in clinical trials. In qualitatively evaluated
      observational studies, switching between forms of antiepileptic drug (innovator
      to generic, generic to generic) may increase the risk of hospitalization
      (strength of evidence: low), hospital stay duration (strength of evidence: low),
      and a composite end point of medical service utilization (strength of evidence:
      insufficient) but may not increase outpatient service utilization (strength of
      evidence: low). Data are limited predominantly to carbamazepine, phenytoin, and
      valproic acid. Clinical trials are limited by small sample size, short-term
      nature, and lack of specification of A-rated generic products (generics that the
      United States Food and Drug Administration has deemed bioequivalent to the
      innovator drug). Observational trials lack full accounting for confounders and
      have inherent limitations. With a low strength of evidence, it appears that
      initiating an innovator or generic antiepileptic drug will provide similar
      efficacy, tolerability, and safety but that switching from one form to the other
      may be associated with more hospitalizations and longer hospital stays.

PMID- 22461123
TI  - Vitamin D supplementation: what's known, what to do, and what's needed.
AB  - The use of vitamin D supplements to prevent and treat a wide range of illnesses
      has increased substantially over the last decade. Epidemiologic evidence links
      vitamin D deficiency to autoimmune disease, cancer, cardiovascular disease,
      depression, dementia, infectious diseases, musculoskeletal decline, and more. The
      Institute of Medicine published an exhaustive report in 2010 that concluded that
      vitamin D supplementation for indications other than musculoskeletal health was
      not adequately supported by evidence and that most North Americans receive
      sufficient vitamin D from their diet and sun exposure. These conclusions are at
      odds with some clinical practice guidelines; thus, we sought to summarize the
      best available evidence regarding the benefits of vitamin D supplementation, to
      examine the potential risks, and to provide practical dosing advice. The adequacy
      of vitamin D stores is determined by measuring the 25-hydroxyvitamin D serum
      concentrations. The demarcations between deficiency (< 20 ng/ml), insufficiency
      (20-30 ng/ml), and optimal (30-80 ng/ml) serum concentrations are controversial.
      Vitamin D in doses of 800-5000 IU/day improve musculoskeletal health (e.g.,
      reduces the rate of fractures and falls in older adults (aged >= 65 yrs). In
      patients with documented vitamin D deficiency, a cumulative dose of at least
      600,000 IU administered over several weeks appears to be necessary to replenish
      vitamin D stores. Single large doses of 300,000-500,000 IU should be avoided.
      Vitamin D supplementation should not be offered routinely to other patient
      populations. Although results from some prospective clinical trials are
      promising, most have not been robustly designed and executed. The decision by
      young, otherwise healthy adults to take vitamin D in doses of 2000 IU/day or
      lower is unlikely to cause harm. For patients who are not at risk for developing
      vitamin D deficiency, sensible sun exposure is an inexpensive and enjoyable way
      to maintain vitamin D stores.

PMID- 22461122
TI  - Cost-effectiveness of cytochrome P450 2C19 genotype screening for selection of
      antiplatelet therapy with clopidogrel or prasugrel.
AB  - STUDY OBJECTIVE: To estimate the cost-effectiveness of genotype-guided selection
      of antiplatelet therapy compared with selecting clopidogrel or prasugrel
      irrespective of genotype. DESIGN: Decision model based on event occurrence in the
      Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet
      Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38.
      PATIENTS: Simulated cohort of patients with acute coronary syndrome scheduled to
      undergo percutaneous coronary intervention (PCI), consisting of three arms: those
      receiving genotype-guided antiplatelet therapy with clopidogrel or prasugrel,
      those receiving clopidogrel regardless of genotype, and those receiving prasugrel
      regardless of genotype. MEASUREMENTS AND MAIN RESULTS: All three arms of the
      model incorporated the probability that patients would experience a
      cardiovascular event (death from cardiovascular causes, nonfatal myocardial
      infarction, or nonfatal stroke), a bleeding event (major or minor bleeding), or
      no event while receiving antiplatelet therapy during the 15 months after the
      scheduled PCI. The cytochrome P450 (CYP) 2C19 genotype determined antiplatelet
      drug selection in the genotyping group. Cost-effectiveness was expressed as the
      incremental cost-effectiveness ratio (ICER) for each event avoided in the
      genotype-guided therapy arm versus the other two arms. Genotype-guided
      antiplatelet therapy was dominant, or more effective and less costly, when
      compared with the selection of clopidogrel (ICER -$6760 [95% confidence interval
      (CI) -$6720 to -$6790]) or prasugrel (ICER -$11,710 [95% CI -$11,480 to 
      $11,950]) for all patients without regard to genotype. Genotype-guided therapy
      that included generic clopidogrel was dominant to prasugrel for all patients
      (ICER -$27,160 [95% CI -$27,890 to -$26,420]). Cost savings were not evident when
      genotype-guided therapy that included generic clopidogrel was compared with
      generic clopidogrel for all patients (ICER $2300 [95% CI $2290 to $2320]).
      [Correction added after online publication 12-Mar-2012: In the previous sentence 
      $2300 has been corrected as $2300.]. CONCLUSION: Genotype-guided antiplatelet
      therapy selection may be more cost-effective and may provide more clinical value
      due to fewer adverse outcomes.

PMID- 22461124
TI  - Everolimus: targeted therapy on the horizon for the treatment of breast cancer.
AB  - The mammalian target of rapamycin (mTOR) is a signaling kinase of the
      phosphatidylinositol 3-kinase/protein kinase B (also known as Akt) signaling
      pathway that mediates cell growth and metabolism. Dysregulation of the mTOR
      pathway creates a favorable environment for the development and progression of
      many cancers, including breast cancer, and is associated with the development of
      resistance to endocrine therapy and to the anti-human epidermal growth factor
      receptor-2 (HER2) monoclonal antibody trastuzumab. Therefore, the addition of
      mTOR inhibitors to conventional breast cancer therapy has the potential to
      enhance therapeutic efficacy and/or overcome innate or acquired resistance.
      Everolimus, an mTOR inhibitor with demonstrated preclinical activity against
      breast cancer cell lines, has been shown to reverse Akt-induced resistance to
      hormonal therapy and trastuzumab. Phase I-II clinical trials have demonstrated
      that everolimus has promising clinical activity in women with HER2-positive, HER2
      negative, and estrogen receptor-positive breast cancer when combined with HER2
      targeted therapy, cytotoxic chemotherapy, and hormonal therapy, respectively.
      Everolimus is generally well tolerated; hematologic abnormalities and stomatitis
      are most common adverse events when this drug is combined with cytotoxic
      chemotherapy. Based on these promising results, everolimus is currently under
      evaluation in a series of phase III Breast Cancer Trials of Oral Everolimus
      (BOLERO) trials of women with HER2-positive and estrogen receptor-positive breast
      cancer. Results of these trials will help to establish the role of everolimus in
      the treatment of clinically important breast cancer subtypes.

PMID- 22461125
TI  - Importance of direct patient care in advanced pharmacy practice experiences.
AB  - The Accreditation Council for Pharmacy Education issued revised standards
      (Standards 2007) for professional programs leading to the Doctor of Pharmacy
      degree in July 2007. The new standards require colleges and schools of pharmacy
      to provide pharmacy practice experiences that include direct interaction with
      diverse patient populations. These experiences are to take place in multiple
      practice environments (e.g., community, ambulatory care, acute care medicine,
      specialized practice areas) and must include face-to-face interactions between
      students and patients, and students and health care providers. In 2009, the
      American College of Clinical Pharmacy (ACCP) identified concerns among their
      members that training for some students during the fourth year of pharmacy
      curriculums are essentially observational experiences rather than encounters
      where students actively participate in direct patient care activities. These ACCP
      members also stated that there is a need to identify effective mechanisms for
      preceptors to balance patient care responsibilities with students' educational
      needs in order to fully prepare graduates for contemporary, patient-centered
      practice. The 2010 ACCP Educational Affairs Committee was charged to provide
      recommendations to more effectively foster the integration of pharmacy students
      into direct patient care activities during advanced pharmacy practice experiences
      (APPEs). In this commentary, the benefits to key stakeholders (pharmacy students,
      APPE preceptors, clerkship sites, health care institutions, academic pharmacy
      programs) of this approach are reviewed. Recommendations for implementation of
      direct patient care experiences are also provided, together with discussion of
      the practical issues associated with delivery of effective APPE. Examples of
      ambulatory care and acute care APPE models that successfully integrate pharmacy
      students into the delivery of direct patient care are described. Enabling
      students to engage in high-quality patient care experiences and to assume
      responsibility for drug therapy outcomes is achievable in a variety of practice
      settings. In our opinion, such an approach is mandatory if contemporary pharmacy
      education is to be successful in producing a skilled workforce capable of
      affecting drug therapy outcomes.

PMID- 22461126
TI  - High host density favors greater virulence: a model of parasite-host dynamics
      based on multi-type branching processes.
AB  - We use a multitype continuous time Markov branching process model to describe the
      dynamics of the spread of parasites of two types that can mutate into each other
      in a common host population. While most mathematical models for the virulence of
      infectious diseases focus on the interplay between the dynamics of host
      populations and the optimal characteristics for the success of the pathogen, our
      model focuses on how pathogen characteristics may change at the start of an
      epidemic, before the density of susceptible hosts decline. We envisage animal
      husbandry situations where hosts are at very high density and epidemics are
      curtailed before host densities are much reduced. The use of three pathogen
      characteristics: lethality, transmissibility and mutability allows us to
      investigate the interplay of these in relation to host density. We provide some
      numerical illustrations and discuss the effects of the size of the enclosure
      containing the host population on the encounter rate in our model that plays the
      key role in determining what pathogen type will eventually prevail. We also
      present a multistage extension of the model to situations where there are several
      populations and parasites can be transmitted from one of them to another. We
      conclude that animal husbandry situations with high stock densities will lead to
      very rapid increases in virulence, where virulent strains are either more
      transmissible or favoured by mutation. Further the process is affected by the
      nature of the farm enclosures.

PMID- 22461128
TI  - Commentary: When in Rome? Integration and the rates of mental illness in black
      and minority ethnic youth.

PMID- 22461127
TI  - Cohort Profile: Longitudinal Investigations into Supportive and Ancillary health
      services.
AB  - The Longitudinal Investigations into Supportive and Ancillary health services
      (LISA) study is a cohort of people living with HIV/AIDS who have ever accessed
      anti-retroviral therapy (ART) in British Columbia, Canada. The LISA study was
      developed to better understand the outcomes of people living with HIV with
      respect to supportive services use, socio-demographic factors and quality of
      life. Between July 2007 and January 2010, 1000 participants completed an
      interviewer-administered questionnaire that included questions concerning medical
      history, substance use, social and medical support services, food and housing
      security and other social determinants of health characteristics. Of the 1000
      participants, 917 were successfully linked to longitudinal clinical data through
      the provincial Drug Treatment Program. Within the LISA cohort, 27% of the
      participants are female, the median age is 39 years and 32% identify as
      Aboriginal. Knowledge translation activities for LISA include the creation of
      plain language summaries, internet resources and arts-based engagement activities
      such as Photovoice. 

PMID- 22461129
TI  - Predicting the extent of heterogeneity in meta-analysis, using empirical data
      from the Cochrane Database of Systematic Reviews.
AB  - BACKGROUND: Many meta-analyses contain only a small number of studies, which
      makes it difficult to estimate the extent of between-study heterogeneity.
      Bayesian meta-analysis allows incorporation of external evidence on
      heterogeneity, and offers advantages over conventional random-effects meta
      analysis. To assist in this, we provide empirical evidence on the likely extent
      of heterogeneity in particular areas of health care. METHODS: Our analyses
      included 14 886 meta-analyses from the Cochrane Database of Systematic Reviews.
      We classified each meta-analysis according to the type of outcome, type of
      intervention comparison and medical specialty. By modelling the study data from
      all meta-analyses simultaneously, using the log odds ratio scale, we investigated
      the impact of meta-analysis characteristics on the underlying between-study
      heterogeneity variance. Predictive distributions were obtained for the
      heterogeneity expected in future meta-analyses. RESULTS: Between-study
      heterogeneity variances for meta-analyses in which the outcome was all-cause
      mortality were found to be on average 17% (95% CI 10-26) of variances for other
      outcomes. In meta-analyses comparing two active pharmacological interventions,
      heterogeneity was on average 75% (95% CI 58-95) of variances for non
      pharmacological interventions. Meta-analysis size was found to have only a small
      effect on heterogeneity. Predictive distributions are presented for nine
      different settings, defined by type of outcome and type of intervention
      comparison. For example, for a planned meta-analysis comparing a pharmacological
      intervention against placebo or control with a subjectively measured outcome, the
      predictive distribution for heterogeneity is a log-normal (-2.13, 1.58(2))
      distribution, which has a median value of 0.12. In an example of meta-analysis of
      six studies, incorporating external evidence led to a smaller heterogeneity
      estimate and a narrower confidence interval for the combined intervention effect.
      CONCLUSIONS: Meta-analysis characteristics were strongly associated with the
      degree of between-study heterogeneity, and predictive distributions for
      heterogeneity differed substantially across settings. The informative priors
      provided will be very beneficial in future meta-analyses including few studies.

PMID- 22461130
TI  - Comparative effectiveness of statin plus fibrate combination therapy and statin
      monotherapy in patients with type 2 diabetes: use of propensity-score and
      instrumental variable methods to adjust for treatment-selection bias.
AB  - PURPOSE: Type 2 diabetes is associated with increased cardiovascular risk. The
      comparative effectiveness of statin plus fibrate combination therapy and statin
      monotherapy in reducing risk of cardiovascular disease in real-world settings is
      unknown. METHODS: A retrospective database analysis was performed using a large
      managed care claims database of patients identified with type 2 diabetes based on
      diagnosis codes from January 2002 through December 2003 and continuously enrolled
      for the entire study period, 5.5 years. A statin plus fibrate combination therapy
      group (patients who used statins less than 6 months and augmented with fibrates
      for more than 6 months) and a statin monotherapy group (patients who used statins
      persistently) among patients with type 2 diabetes were followed for 3 years to
      examine the relationship between the intervention and cardiovascular events using
      a multivariable logistic regression model, propensity score method, and
      instrumental variable approach. RESULTS: The statin plus fibrate combination
      therapy group of 318 and the statin monotherapy group of 9928 were identified
      from 75,515 diabetics. After adjusting for factors that can impact cardiovascular
      outcomes, the combination therapy group did not significantly experience a
      reduction in cardiovascular disease, as compared with the statin monotherapy
      group (OR = 0.77; p = 0.083). The statin plus fibrate combination therapy group
      was significantly associated with a reduction in cardiovascular events after
      propensity matching (OR = 0.53; p = 0.002). Using the physician prescribing
      preference instrument to adjust for unmeasured confounding, we did not find
      evidence that subjects in the statin plus fibrate combination therapy group
      versus stain monotherapy group experienced a significant reduction in
      cardiovascular events (p = 0.124). CONCLUSIONS: We did not find a difference in
      effectiveness regarding cardiovascular outcomes between the statin plus fibrate
      combination therapy and the statin monotherapy after controlling for hidden bias.

PMID- 22461131
TI  - Coexpression of stemness factors Oct4 and Nanog predict liver resection.
AB  - BACKGROUND: Oct4 and Nanog are two major transcription factors related to the
      stem cell self-renewal and differentiation. The aim of this study was to evaluate
      the correlation between these two stemness markers with recurrence, metastasis,
      and prognosis of hepatocellular carcinoma (HCC). METHODS: Expression of Oct4 and
      Nanog was evaluated by immunohistochemistry in a random cohort of 228 HCC
      patients (cohort A), predominantly hepatitis B related, and validated in another
      independent cohort of 95 patients (cohort B). Survival analysis was performed by
      univariate and multivariate analyses. Oct4 and Nanog expression levels in 5 HCC
      cell lines with different metastatic potential were detected by Western blot
      assay and quantitative real-time PCR assay. RESULTS: In tissue microarrays,
      coexpression of Oct4 and Nanog was dramatically associated with big tumor size (P
      = .001) and vascular invasion (P = .02) and was an independent predictor of
      postoperative recurrence (hazard ratio [HR] = 1.57, 95 % confidence interval [95
      % CI] 1.21-2.04, P = .01) and poor prognosis (HR = 2.20, 95 % CI 1.71-2.88, P <
      .001). This association was further validated in patients in cohort B.
      Importantly, this correlation remained significant in patients with early-stage
      HCC or alpha-fetoprotein (AFP) negative HCC. In addition, expression of Oct4 and
      Nanog increased in a concordant manner with the increase of metastatic potential
      in human HCC cell lines. CONCLUSIONS: Coexpression of stemness markers Oct4 and
      Nanog in HCC indicated the aggressive tumor behaviors and predicted a worse
      clinical outcome, which may be a useful biomarker to identify patients at high
      risk of postoperative recurrence.

PMID- 22461132
TI  - Osteopontin expression is associated with improved survival in patients with
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Osteopontin (OPN) is a secreted protein of the extracellular matrix.
      It has been used as a marker for tumor aggressiveness and correlated with
      clinical outcomes in several solid tumors, such as liver, lung, and breast. We
      determined the OPN expression and its influence on survival in patients with
      resected pancreatic adenocarcinoma. METHODS: Tissue microarrays were constructed
      from 245 resected pancreatic adenocarcinomas. Immunohistochemical staining for
      OPN was undertaken and compared to normal pancreas (n = 12). OPN expression was
      then correlated with patient demographics, tumor size, grade, node, and margin
      status. Survival curves were created by the Kaplan-Meier method and compared by
      log rank analysis. RESULTS: In total, 181 (74 %) of pancreatic adenocarcinoma
      tissues expressed OPN compared to 7 (58 %) of normal controls (p = 0.004).
      Expression was observed predominantly in the cytoplasm of the tumor cells. The
      median and 2 year overall survival was longer when OPN was expressed (17.1 vs.
      11.6 months, and 38 vs. 24 %, respectively, p = 0.04). Multivariate analysis
      showed OPN expression and T stage to be independent predictors of overall
      survival, while other histopathologic factors such as tumor grade, tumor size,
      and nodal status were not. CONCLUSIONS: These results suggest that the presence
      of OPN expression in pancreatic adenocarcinoma may have a protective effect
      independent of tumor stage. This emphasizes the importance of the interaction
      between pancreatic cancer cells and their stromal elements.

PMID- 22461133
TI  - Clinical features of bipolar disorder comorbid with anxiety disorders differ
      between men and women.
AB  - BACKGROUND: Anxiety disorders are commonly comorbid with bipolar disorder (BP)
      and may worsen course of illness, but differential impact of specific anxiety
      disorders in men and women remains unknown. METHODS: We measured the impact of
      comorbid panic disorder (PD), social phobia, specific phobia, and obsessive
      compulsive disorder (OCD) in 460 women and 276 men with Bipolar I Disorder (BPI)
      or schizoaffective disorder, bipolar type from the National Institute of Mental
      Health Bipolar Genetics Initiative. We compared clinical characteristics in BP
      with and without each anxiety disorder in men and women separately correcting for
      family relatedness. RESULTS: Comorbid PD, OCD, and specific phobia were more
      common in women with BP than men. Comorbid social phobia correlated with
      increased risk of alcohol abuse in BP women, but not men. Women with comorbid PD
      attended fewer years of school. Comorbidity with OCD was associated with earlier
      age at the onset of BP for both genders. Comorbid PD, OCD, and specific phobia
      were associated with more antidepressant trials in BP, across both genders,
      compared to BP patients without these anxiety disorders. CONCLUSION: In BP,
      comorbid anxiety disorders are associated with increased risk for functional
      impairment, and women had differently associated risks than men. Clinicians
      should be aware of an increased risk for comorbid PD, OCD, and specific phobia in
      women with BP, and an increased risk of alcohol abuse in women with BD and
      comorbid social phobia.

PMID- 22461135
TI  - Thyroglossal duct cysts in adults treated by ethanol sclerotherapy: a pilot study
      of a nonsurgical technique.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the effect of ethanol sclerotherapy on the
      thyroglossal duct cyst (TDC). STUDY DESIGN: Prospective case series. METHODS:
      Patients with primary TDC were enrolled. The volume of the TDC was calculated
      using the following formula: length * width * height * pi/6. Under sonographic
      guidance, ethanol was slowly instilled into the TDC cavity after the cyst fluid
      was aspirated. The procedure was performed in an outpatient setting. RESULTS: A
      total of eight patients were recruited for this study, but two of them did not
      receive sclerotherapy. One patient refused treatment after obtaining initial
      consent, and another patient was not treated due to a technical issue. The median
      follow-up duration was 21 months. The median cyst volume was 3.5 mL. Of the six
      patients given sclerotherapy, recurrent TDC occurred in one patient. As expected,
      the TDC persisted in the two patients who had not undergone sclerotherapy. Two
      patients experienced moderate pain after the procedure that was well controlled
      with oral analgesics. No major complications arose, and no patient needed
      hospitalization because of treatment complications. CONCLUSIONS: Percutaneous
      ethanol sclerotherapy is an effective minimally invasive modality of therapy for
      TDC. Further studies with longer follow-up are warranted.

PMID- 22461134
TI  - Health effects of identifying patients with undiagnosed obstructive sleep apnea
      in the preoperative clinic: a follow-up study.
AB  - BACKGROUND: Undiagnosed obstructive sleep apnea (OSA) is a highly prevalent
      breathing disorder. The purpose of this study was to determine the effects of
      preoperative screening and subsequent treatment for OSA on the health of
      patients. METHODS: We conducted a two-year follow-up study of patients previously
      enrolled in a large prospective study in which patients were given the STOP
      questionnaire for OSA screening (n = 2,467). All patients who underwent a
      polysomnography were considered eligible (n = 211) and were asked to complete a
      paper-based mailed questionnaire. The severity of OSA, comorbidities, and
      treatment modalities and their effects were evaluated from the returned
      questionnaire. Research ethics board approval was obtained and returning the
      questionnaire implied informed patient consent. RESULTS: The response rate was
      67%. One hundred twenty-eight (82%) of the 156 patients who responded had OSA
      established by polysomnography. Among these 128 patients with OSA, 88 (69%) were
      prescribed continuous positive airway pressure (CPAP) therapy and 40 (31%) were
      prescribed other (non-CPAP) treatment. Among those 88 patients receiving CPAP, 40
      (45%) were compliant and 48 (55%) were non-compliant. The CPAP compliant patients
      had a greater reduction in medication for comorbidities than the CPAP non
      compliant or the other treatment group (38% vs 3% vs 0%, respectively; P <
      0.001). A significant improvement in snoring, sleep quality, and daytime
      sleepiness was reported by CPAP compliant users compared with CPAP non-compliant
      or other treatment groups (P < 0.001). CONCLUSION: The preoperative patients who
      were identified to have OSA and were compliant with CPAP use may have health
      benefits in terms of improved snoring, sleep quality, and daytime sleepiness.
      Timely diagnosis and treatment compliance may reduce symptoms of OSA and severity
      of associated comorbidities along with a reduction in medications.

PMID- 22461136
TI  - Determinants of quality of life in children with chronic somatic disease: pilot
      data from the GapS Questionnaire.
AB  - PURPOSE: Quality of life (QoL) is a ubiquitous yet poorly defined concept; the
      precise determinants of QoL are rarely identified. We used pilot data from the
      GapS Questionnaire to investigate the most important determinants of QoL in
      children with chronic somatic illness. METHODS: We enrolled 92 participants
      including 60 parents and 32 of their children. The sample comprised rheumatology,
      diabetes, epilepsy, gastroenterology, cystic fibrosis, and day unit patients.
      Trained interviewers administered the GapS Questionnaire to parents, and to
      children if >= 10 years. We determined the relative importance of different items
      for QoL. RESULTS: Child participants had a mean age of 14.7 years. Children
      identified "having good friendships", "being happy most days", and "getting along
      with parents" as most important. Parents ranked most highly "being allowed to do
      all the things you like doing", "getting told you have done a good job at
      something", and "being physically able to do everything you enjoy doing".
      CONCLUSIONS: Physical health items were not as important as social and
      psychological determinants of QoL in our pilot sample.

PMID- 22461137
TI  - Pre-diagnosis quality of life (QoL) in patients with hematuria: comparison of
      bladder cancer with other causes.
AB  - PURPOSE: To examine quality of life (QoL), health status, sexual function, and
      anxiety in patients with primary hematuria who later appear to have bladder
      cancer (BC) and patients with other diagnoses. METHODS: From July 2007 to July
      2010, 598 patients with primary hematuria were enrolled in this prospective,
      multicenter study. Questionnaires (WHOQOL-BREF, SF-12, IIEF, STAI-10-item Trait)
      were completed before cystoscopy. Diagnosis was subsequently derived from medical
      files. BC patients were compared with patients with other causes of hematuria.
      RESULTS: Cancer was diagnosed in 131 patients (21.9 %), including 102 patients
      (17.1 %) with BC. No differences were found in the WHOQOL-BREF versus SF-12
      psychological or physical health domains. The erectile function was significantly
      worse in the BC group (9.3 vs. 14.6 for OC, p = 0.02). Patients with muscle
      invasive BC (MIBC) had the lowest percentage anxious personalities of all BC
      patients (p = 0.04). CONCLUSIONS: Cancer was found in 21.9 % of the patients with
      hematuria. Pre-diagnosis patients with BC have comparable QoL and HS to patients
      with OC. Erectile dysfunction was highest in patients with BC. MIBC patients had
      the lowest percentage anxious personalities of the patients with BC.

PMID- 22461138
TI  - Genetic overlap of schizophrenia and bipolar disorder in a high-density linkage
      survey in the Portuguese Island population.
AB  - Recent family and genome-wide association studies strongly suggest shared genetic
      risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage
      studies have not been used to test for statistically significant genome-wide
      overlap between them. Forty-seven Portuguese families with sibpairs concordant
      for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were
      genotyped for over 57,000 markers using the Affymetrix 50K Xba SNP array. NPL and
      Kong and Cox LOD scores were calculated in Merlin for all three phenotypes.
      Empirical significance was determined using 1,000 gene-dropping simulations.
      Significance of genome-wide genetic overlap between SZ and BP was determined by
      the number of simulated BP scans having the same number of loci jointly linked
      with the real SZ scan, and vice versa. For all three phenotypes, a number of
      regions previously linked in this sample remained so. For BP, chromosome 1p36
      achieved significance (11.54-15.71 MB, LOD = 3.51), whereas it was not even
      suggestively linked at lower marker densities, as did chromosome 11q14.1 (89.32
      90.15 MB, NPL = 4.15). Four chromosomes had loci at which both SZ and BP had NPL
      >= 1.98, which was more than would be expected by chance (empirical P = 0.01
      using simulated SZ scans; 0.07 using simulated BP scans), although they did not
      necessarily meet criteria for suggestive linkage individually. These results
      suggest that high-density marker maps may provide greater power and precision in
      linkage studies than lower density maps. They also further support the hypothesis
      that SZ and BP share at least some risk alleles.

PMID- 22461140
TI  - Analysis of SF3B1 mutations in monoclonal B-cell lymphocytosis.

PMID- 22461139
TI  - Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission
      tomography predicts early stroke recurrence.
AB  - OBJECTIVE: Symptomatic carotid stenosis is associated with a 3-fold risk of early
      stroke recurrence compared to other stroke subtypes. Current carotid imaging
      techniques rely on estimating plaque-related lumen narrowing but do not evaluate
      intraplaque inflammation, a key mediator of plaque rupture and thromboembolism.
      Using combined (18) F-fluorodeoxyglucose positron-emission tomography (FDG
      PET)/computed tomography, we investigated the relation between inflammation
      related FDG uptake and stroke recurrence. METHODS: Consecutive patients with a
      recent (median, 6.5 days; interquartile range, 4-8) stroke, transient ischemic
      attack (TIA), or retinal embolism and ipsilateral carotid stenosis (>=50%) were
      included. FDG uptake was quantified as mean standardized uptake values (SUVs,
      g/ml). Patients were followed prospectively for stroke recurrence. RESULTS: Sixty
      patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two
      percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in
      ipsilateral carotid plaque was greater in patients with early recurrent stroke
      (mean SUV, 1.85 g/ml; standard deviation [SD], 0.44 vs 1.58 g/ml; SD, 0.32, p =
      0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than
      a 2.14 g/ml threshold were 80% (95% confidence interval [CI], 41.8-99.2) versus
      22.9% (95% CI, 12.3-40.3) with SUV <=2.14 g/ml (log-rank, p < 0.0001). In a Cox
      regression model including age and degree of stenosis (50-69% or >=70%), mean
      plaque FDG uptake was the only independent predictor of stroke recurrence
      (adjusted hazard ratio, 6.1; 95% CI, 1.3-28.8; p = 0.02). INTERPRETATION: In
      recently symptomatic carotid stenosis, inflammation-related FDG uptake was
      associated with early stroke recurrence, independent of the degree of stenosis.
      Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who
      may be selected for immediate revascularization or intensive medical treatment.

PMID- 22461141
TI  - Clinical practice recommendations for the treatment of Alport syndrome: a
      statement of the Alport Syndrome Research Collaborative.
AB  - We present clinical practice recommendations for the treatment of children with
      Alport syndrome who are not enrolled in clinical trials. Our goal is to promote
      early initiation of a standard therapeutic approach that will facilitate
      assessment of the safety and efficacy of the protocol. The treatment protocol is
      based on the reduction of proteinuria, intraglomerular pressure, and renal
      fibrosis via interference with the renin-angiotensin-aldosterone system.

PMID- 22461142
TI  - Genetics of pediatric renal tumors.
AB  - Wilms tumor (WT) accounts for approximately 95 % of all pediatric renal tumors,
      with a peak incidence between 2 and 3 years of age. It occurs in sporadic and
      congenital forms, the latter often occurring before 1 year of age. Incidence
      declines with age, and WT rarely is observed in adults. WT is an embryonal tumor
      of the kidney caused by aberrant proliferation of early metanephric kidney cells.
      It can arise from more than one developmental error and therefore several
      subtypes can be defined. WT1, a zinc-finger transcription factor, was identified
      as the first WT gene. Other genes frequently altered somatically in subsets of WT
      are CTNNB1 and WTX; both genes influence the Wnt signalling pathway. Imprinting
      alterations of genes in 11p15 are also observed in a subset of WTs. Other
      pediatric renal tumors occur less often, e.g. malignant rhabdoid tumor of the
      kidney, clear-cell sarcoma, desmoplastic small-round-cell tumors, congenital
      mesoblastic nephroma, renal cell carcinoma of childhood, renal primitive
      neuroectodermal tumors, renal medullary carcinoma, and synovial sarcoma of the
      kidney. In most of these, characteristic genetic alterations have been identified
      that help in the unequivocal diagnosis of these childhood renal cancers that are
      often difficult to distinguish.

PMID- 22461143
TI  - The linguistic roots of Modern English anatomical terminology.
AB  - Previous research focusing on Classical Latin and Greek roots has shown that
      understanding the etymology of English anatomical terms may be beneficial for
      students of human anatomy. However, not all anatomical terms are derived from
      Classical origins. This study aims to explore the linguistic roots of the Modern
      English terminology used in human gross anatomy. By reference to the Oxford
      English Dictionary, etymologies were determined for a lexicon of 798 Modern
      English gross anatomical terms from the 40(th) edition of Gray's Anatomy.
      Earliest traceable language of origin was determined for all 798 terms; language
      of acquisition was determined for 747 terms. Earliest traceable languages of
      origin were: Classical Latin (62%), Classical Greek (24%), Old English (7%), Post
      Classical Latin (3%), and other (4%). Languages of acquisition were: Classical
      Latin (42%), Post-Classical Latin (29%), Old English (8%), Modern French (6%),
      Classical Greek (5%), Middle English (3%), and other (7%). While the roots of
      Modern English anatomical terminology mostly lie in Classical languages
      (accounting for the origin of 86% of terms), the anatomical lexicon of Modern
      English is actually much more diverse. Interesting and perhaps less familiar
      examples from these languages and the methods by which such terms have been
      created and absorbed are discussed. The author suggests that awareness of
      anatomical etymologies may enhance the enjoyment and understanding of human
      anatomy for students and teachers alike.

PMID- 22461144
TI  - A carnitine-acylcarnitine carrier protein, MoCrc1, is essential for pathogenicity
      in Magnaporthe oryzae.
AB  - The rice blast fungus Magnaporthe oryzae forms a specialized infection structure
      called an appressorium to breach the host-plant epidermis for successful
      infection. In this study, a mutant defective in appressorial penetration was
      isolated by a mutagenesis approach, in which an exogenous DNA fragment was found
      to be inserted into the first exon of MoCRC1. This gene encodes a putative
      carnitine-acylcarnitine carrier protein that is widely conserved among eukaryotic
      organisms. Deletion of MoCRC1 severely reduces appressorium turgor generation,
      appressorial penetration, and development of infection hyphae. The null mutant of
      MoCRC1 lost pathogenicity on intact and abraded host leaves. MoCRC1 was also
      found to be required for growth on minimal medium containing sodium acetate or
      olive oil. Moreover, the transformed MoCrc1-eGFP fusion protein was expressed
      throughout the infection process. Our results suggest that the carnitine
      acylcarnitine carrier protein plays vital roles in appressorium-mediated
      infection and is essential for pathogenesis of M. oryzae and perhaps other
      phytopathogenic fungi.

PMID- 22461146
TI  - Multimodal optical imaging with multiphoton microscopy and optical coherence
      tomography.
AB  - Two types of combined multiphoton microscopy and optical coherence tomography
      (MPM/OCT) are compared for multimodal optical imaging. Single-scale multiphoton
      microscopy and optical coherence microscopy (MPM/OCM) is shown to acquire
      multiple contrasts from MPM and OCT simultaneously. Multi-scale MPM/OCT is shown
      to provide multiple field-of-views (FOVs), where OCT provides tissue level
      imaging and MPM provides cellular level imaging. In both types, the MPM includes
      two channels which are two-photon excited fluorescence (TPEF) and second harmonic
      generation (SHG). Representative images using each system are demonstrated on
      biological specimens. A detailed comparison of the two types of MPM/OCT shows
      that each system has its own pros and cons. MPM/OCM is high-resolution but with
      limited FOV, and OCM may or may not provide additional information than MPM
      depending on the samples. Multi-scale MPM/OCT can change FOV but need both low
      and high NA objectives. For future development, the two types of MPM/OCT can be
      further integrated to achieve both functions on a single system.

PMID- 22461145
TI  - Identification of an Hsp90 mutation that selectively disrupts cAMP/PKA signaling
      in Saccharomyces cerevisiae.
AB  - The molecular chaperone Hsp90 cooperates with multiple cochaperone proteins as it
      promotes the folding and activation of diverse client proteins. Some cochaperones
      regulate the ATPase activity of Hsp90, while others appear to promote Hsp90
      interaction with specific types of client proteins. Through its interaction with
      the adenylate cyclase Cyr1, the Sgt1 cochaperone modulates the activity of the
      cAMP pathway in Saccharomyces cerevisiae. A specific mutation in yeast Hsp90,
      hsc82-W296A, or a mutation in Sgt1, sgt1-K360E, resulted in altered transcription
      patterns genetically linked to the cAMP pathway. Hsp90 interacted with Cyr1 in
      vivo and the hsc82-W296A mutation resulted in reduced accumulation of Cyr1. Hsp90
      Sgt1 interaction was altered by either the hsc82-W296A or sgt1-K360E mutation,
      suggesting defective Hsp90-Sgt1 cooperation leads to reduced Cyr1 activity.
      Microarray analysis of hsc82-W296A cells indicated that over 80 % of all
      transcriptional changes in this strain may be attributed to altered cAMP
      signaling. This suggests that a majority of the cellular defects observed in
      hsc82-W296A cells are due to altered interaction with one specific essential
      cochaperone, Sgt1 and one essential client, Cyr1. Together our results indicate
      that specific interaction of Hsp90 and Sgt1 with Cyr1 plays a key role in
      regulating gene expression, including genes involved in polarized morphogenesis.

PMID- 22461147
TI  - Niobium(V) oxynitride: synthesis, characterization, and feasibility as anode
      material for rechargeable lithium-ion batteries.
AB  - The decomposition reaction of niobium(V) oxytrichloride ammoniate to the
      oxynitride of niobium in the 5+ oxidation state was developed in a methodological
      way. By combining elemental analysis, Rietveld refinements of X-ray and neutron
      diffraction data, SEM and TEM, the sample compound was identified as
      approximately 5 nm-diameter particles of NbO(1.3(1))N(0.7(1)) crystallizing with
      baddeleyite-type structure. The thermal stability of this compound was studied in
      detail by thermogravimetric/differential thermal analysis and temperature
      dependent X-ray diffraction. Moreover, the electrochemical uptake and release by
      the galvanostatic cycling method of pure and carbon-coated NbO(1.3(1))N(0.7(1))
      versus lithium was investigated as an example of an Li-free transition-metal
      oxynitride. The results showed that reversible capacities as high as 250 and 80 A
      h  kg(-1) can be reached in voltage ranges of 0.05-3 and 1-3 V, respectively.
      Furthermore, a plausible mechanism for the charge-discharge reaction is proposed.

PMID- 22461148
TI  - sigma-Accepting properties of a chlorobismuthine ligand.
AB  - BiZness as usual? Not exactly! The bismuth atom of the tridentate
      diphosphinobismuthine (o-(Ph(2)P)C(6)H(4))(2) BiCl behaves as a Z rather than L
      ligand when in the coordination sphere of late transition metals such as gold.
      The sigma-acceptor behavior of Bi is supported by its disphenoid coordination
      geometry and theoretical studies, which show a Au->Bi interaction.

PMID- 22461149
TI  - Methods for covariate adjustment in cost-effectiveness analysis that use cluster
      randomised trials.
AB  - Statistical methods have been developed for cost-effectiveness analyses of
      cluster randomised trials (CRTs) where baseline covariates are balanced. However,
      CRTs may show systematic differences in individual and cluster-level covariates
      between the treatment groups. This paper presents three methods to adjust for
      imbalances in observed covariates: seemingly unrelated regression with a robust
      standard error, a 'two-stage' bootstrap approach combined with seemingly
      unrelated regression and multilevel models. We consider the methods in a cost
      effectiveness analysis of a CRT with covariate imbalance, unequal cluster sizes
      and a prognostic relationship that varied by treatment group. The cost
      effectiveness results differed according to the approach for covariate
      adjustment. A simulation study then assessed the relative performance of methods
      for addressing systematic imbalance in baseline covariates. The simulations
      extended the case study and considered scenarios with different levels of
      confounding, cluster size variation and few clusters. Performance was reported as
      bias, root mean squared error and CI coverage of the incremental net benefit.
      Even with low levels of confounding, unadjusted methods were biased, but all
      adjusted methods were unbiased. Multilevel models performed well across all
      settings, and unlike the other methods, reported CI coverage close to nominal
      levels even with few clusters of unequal sizes.

PMID- 22461150
TI  - Iron thiolate complexes: efficient catalysts for coupling alkenyl halides with
      alkyl Grignard reagents.
AB  - Ironing out the kinks: Efficient new catalytic systems based on iron thiolates
      are described for the iron-catalyzed cross-coupling of alkyl Grignard reagents
      with alkenyl halides. The reaction is highly chemo- and stereoselective. With
      this new procedure, the use of N-methylpyrrolidone as a co-solvent is no longer
      required.

PMID- 22461151
TI  - The Duero Diatom Index (DDI) for river water quality assessment in NW Spain:
      design and validation.
AB  - Diatom indices developed in certain geographic regions are frequently used
      elsewhere, despite the strong evidence that such metrics are less useful when
      applied in regions other than that where species-environment relationships were
      originally assessed, showing that species have particular autoecological
      requirements in different geographic areas. The goal of this study was to develop
      a new metric, the Duero Diatom Index (DDI), aimed at monitoring water quality in
      Duero basin watercourses (NW Spain). In summer 2008 and 2009, a total of 355
      epilithic diatom samples were collected following standard protocols. The 2008
      samples were used to develop the DDI, whereas the samples collected during 2009
      were used in the index testing. Weighted averages method was used to derive the
      autoecological profiles of diatoms with respect to pH, conductivity, biological
      oxygen demand, ammonia, nitrates, and phosphates. The optimum and tolerance
      values for the measured environmental variables were determined for 137 taxa with
      abundances and frequencies of occurrence above 1%, and subsequent trophic
      indicator and sensitivity values were defined for the DDI. The correlation
      between the observed and the diatom-inferred nutrient concentrations was highest
      for phosphates (rho (S) = 0.72). Significant statistical relationship were
      observed between DDI values and the chemistry-based General Quality Index values
      (p = 0.006) and the specific pollution index (SPI) diatom metric (p = 0.04). DDI
      has demonstrated a better correlation with water chemistry than SPI diatom
      metric.

PMID- 22461152
TI  - The burden of illness of osteoporosis in Canadian men.
AB  - There is a dearth of information about the burden of osteoporosis in Canadian
      men. To fill this gap, we conducted a burden of illness study aimed at estimating
      the economic burden attributable to osteoporosis in Canadian men aged 50 years
      and older. Five national data sources were used to estimate health care resource
      utilization and costs (in 2010 Canadian dollars) associated with osteoporosis in
      men. Any information gap was supplemented by using data from provincial and
      community sources. Direct medical costs included costs associated with
      hospitalizations, same day surgeries, emergency room visits, rehabilitation,
      chronic care, long-term care, home care, physician visits, and prescribed
      medications. The value of lost productivity from patients and informal caregivers
      was also determined to provide a societal perspective. Sensitivity analyses were
      conducted to evaluate the impact of key assumptions on the results. In fiscal
      year 2007/2008, the total economic burden of treating and rehabilitating male
      osteoporotic fractures was estimated at $570 million per year, where direct
      medical costs accounted for 86%. Acute care utilization was responsible for 70%
      of all direct costs. About 51% of all hospitalizations were for hip fractures and
      hip fractures alone accounted for 54% of the acute care spending. If a proportion
      of Canadian men were assumed to live in long-term care facilities due to
      osteoporosis, the overall annual cost of osteoporosis would increase from $570
      million to $910 million. Male osteoporosis has a substantial economic burden on
      the Canadian society.

PMID- 22461153
TI  - A convenient method for electron tomography sample preparation using a focused
      ion beam.
AB  - Here we report a new sample preparation method for three-dimensional electron
      tomography. The method uses the standard film deposition and focused ion beam
      (FIB) methods to significantly reduce the problems arising from the projected
      sample thickness at high tilt angles. The method can be used to prepare
      tomography samples that can be imaged up to a +/-75 degrees  tilt range which is
      sufficient for many practical applications. The method can minimize the problem
      of Ga+ contamination, as compared to the case of FIB preparation of rod-shaped
      samples, and provides extended thin regions for standard 2D projection analyses.

PMID- 22461154
TI  - Non responsive celiac disease due to coexisting hereditary fructose intolerance.
AB  - Celiac disease is associated with several genetic disorders, but its association
      with hereditary fructose intolerance is rare. Hereditary fructose intolerance is
      a rare autosomal recessive disease of fructose metabolism presenting as vomiting
      after intake of fructose. An association between these two distinct genetic
      gastrointestinal disorders is important as treatment failure of celiac disease
      calls for careful evaluation for hereditary fructose intolerance. We report a
      patient with an association of these two disorders.

PMID- 22461156
TI  - From the Editor-in-Chief.

PMID- 22461155
TI  - The chemistry of the polycyclic polyprenylated acylphloroglucinols.
AB  - With their fascinating biological profiles and stunningly complex molecular
      architectures, the polycyclic polyprenylated acylphloroglucinols (PPAPs) have
      long provided a fertile playing field for synthetic organic chemists. In
      particular, the recent advent of innovative synthetic methods and strategies
      together with C-C bond-forming reactions and asymmetric catalysis have
      revitalized this field tremendously. Consequently, PPAP targets which once seemed
      beyond reach have now been synthesized. This Review aims to highlight the recent
      achievements in the total synthesis of PPAPs, as well as notable methods
      developed for the construction of the bicyclo[3.3.1] core of these chemically and
      biologically intriguing molecules.

PMID- 22461157
TI  - Bone fragility: current reviews and clinical features.
AB  - Bone strength is determined by a number of important factors, including bone mass
      and bone shape. A reduction in bone strength is clearly related to fracture. Bone
      fragility results from a reduction in bone mass and density. If there is a
      reduction in the connectivity of bone and impact from a mechanical load occurs,
      bone will fracture. Rather than considering bone fragility as being the result of
      a reduced amount of bone, we recognize that bone fragility is the result of
      changes in the material and structural properties of bone. A better understanding
      of the contribution of each component of the material composition and structure,
      and how these interact to maintain whole bone strength is obtained by the study
      of metabolic bone diseases. Disorders of collagen, of mineral content composition
      and distribution, disorders of remodelling and other diseases produce
      abnormalities in the material composition and structure that lead to bone
      fragility.

PMID- 22461158
TI  - The "osteoporosis disease".
AB  - The authors analyze the reason that make osteoporosis a complex, widespread and
      poorly controlled "disease". In their work the authors take into account
      etiopathogenesis, epidemiology, risk factors, diagnosis and therapy. Author's
      attention is focused on management both of patient whit osteoporotic fractures
      and preventive therapy, which are aspects of the osteoporotic desease that should
      not be exclusive problems for the orthopaedic's sourgeon.

PMID- 22461159
TI  - Proximal femural fractures: epidemiology.
AB  - The Authors report briefly about epidemiology and prognosis of proximal femoral
      fractures in elderly people worldwide. Focusing particurarly on Italian
      population, the Authors report on the impact that this pathologic phenomenon has
      on the quality of life of patients and on general population, also from a social
      and economical point of view. A concise overview of the options treatment is also
      presented.

PMID- 22461160
TI  - Vitamin D supplementation in fractured patient: how, when and why.
AB  - Vitamin D, through its action on calcium metabolism, is essential for bone
      physiology. It's also required in a wide range of biological systems to act
      modulating the proliferation and inducing terminal differentiation of a variety
      of normal cells. Actually vitamin D deficiency can impact muscle function and
      increases fall risk in elderly, while severe vitamin D deficiency (< 30 nmol/L)
      is common in patients with fragility fractures. Vitamin D and calcium
      supplementation, in addition to antiosteoporosis treatment after surgery or
      conservative treatment, can ensure optimal recovery and survival, especially in
      hip fractured patients.

PMID- 22461161
TI  - Vertebroplasty and kyphoplasty.
AB  - Vertebral fractures are a major health care problem in Western countries. Pain
      and deformity are the major problems related to these fractures, with an enormous
      impact on the quality of life. Surgery is indicated in patients with concurrent
      spinal instability or neurologic deficit. The cornerstone of management for
      vertebral body fractures without neurological impairment is medical therapy,
      which include analgesics, bed rest, orthoses and rehabilitation. In the majority
      of patients such treatment modalities are effective. However, conservative
      management measures are not indicated for every type of fracture. Two different
      percutaneous minimally invasive vertebral augmentation methods for cement
      application into the vertebral body in the management of symptomatic fractures
      without neurological impairment have been developed, namely vertebroplasty and
      kyphoplasty. Aim of this paper is to give an overview of the state of the art
      about vertebroplasty and kyphoplasty, discussing the indications, techniques,
      results and pitfalls.

PMID- 22461162
TI  - Surgical approach to bone healing in osteoporosis.
AB  - Osteoporotic fractures represent one of the most common cause of disability and
      one of the major voice in the health economic budget in many countries of the
      world. Fragility fractures are especially meta-epiphyseal fractures, in skeletal
      sites with particular biomechanic characteristic (hip, vertebrae), complex and
      with more fragments, with slow healing process (mineralization and remodeling)
      and co-morbidity. The healing of a fracture in osteoporotic bone passes through
      the normal stages and concludes with union of the fracture although the healing
      process is prolonged. Fractures in the elderly osteoporotic patients represent a
      challenge to the orthopaedic surgeons. Osteoporosis does not only increase the
      risk of fracture but also represents a problem in osteofixation of fractures in
      fracture treatment. The major technical problem that surgeons face, is the
      difficulty to obtain a stable fixation of an implant due to osteoporotic bone.
      The load transmitted at the bone-implant interface can often exceed the reduced
      strain tolerance of osteoporotic bone.IN THE TREATMENT OF OSTEOPOROTIC FRACTURES
      IT IS IMPORTANT TO CONSIDER DIFFERENT ASPECTS: general conditions of elderly
      patient and comorbidity, the reduced muscular and bone mass and the increased
      bone fragility, structural modifications as medullary expansion.The aim of
      surgical treatment is to obtain a stable fixation that reduces pain and permits
      an early mobilization.

PMID- 22461163
TI  - Fracture healing and drug therapies in osteoporosis.
AB  - Fracture repair has not been fully optimised and there is opportunity to increase
      the healing rate and reduce the number of complications using pharmacological
      means. While most anti-osteoporosis drugs have been widely tested for their
      ability to decrease the risk of osteoporotic fractures, fragility fractures still
      occur in patients under medical intervention. The primary purpose of this
      systematic review is to understand these underlying mechanisms between bone and
      drug therapies in osteoporosis and the overall promotion of fracture healing and
      callus formation. Databases such as MEDLINE, Google Scholar, EMBASE and CINAHL
      were searched and nine articles met all inclusion criteria. We report that there
      is still large controversy and a need for clinical trials to address the
      deficiencies found in animal models. There is no clear evidence yet as to whether
      complications during the course of healing are attributable to implant anchorage
      problems in osteoporotic bone or to possibly delayed healing in the aged.

PMID- 22461164
TI  - Pharmacological agents and bone healing.
AB  - Osteoporosis is the most common alteration of bone metabolism. It derives from an
      increase in bone resorption with respect to bone formation and is characterized
      by microarchitectural alterations, decreased bone mass and increased risk of
      fracture. The coupling between bone formation and resorption is a fundamental
      concept in skeletal metabolism, and it explains how a certain amount of removed
      tissue can be replaced by the same amount of new bone. Various substances used to
      treat osteoporosis may also be used for orthopaedic conditions such as fracture
      healing, implant fixation, bone grafts and osteonecrosis. Fracture healing
      consists in the replacement of the lost bone by a tissue that has the same
      biomechanical properties as those preceding the fracture. The repair process is
      triggered by the local response to the tissue injury that damaged the continuity
      of bone. The duration of each phase of the healing process can vary
      significantly, depending on the site and characteristics of the fracture, on
      patient related factors and on the treatment choice. While most of the fractures
      heal with conventional treatment, they can also cause permanent damage and
      complications, especially in a certain kind of patients. Osteoporosis and old age
      may contribute in delaying or impairing the reparative process. In animal models
      the healing process is slower in older and/or ovariectomized animals.
      Biomechanical tests have also shown that bone strength is compromised in human
      osteoporotic cadaver bone. The same problems were highlighted in the surgical
      treatment of fractures in osteoporotic patients. Mainly in the treatment of hip
      fractures there is an increased risk of cut-out, re-fractures and implant failure
      in patients with osteoporosis. Preclinical studies have shown that certain
      pharmacological agents (bisphosphonates, strontium ranelate, teriparatide) may
      enhance osseointegration and stimulate reparative processes. They may be
      administered systemically and/or used locally at the fracture site on the implant
      surface. The aim of fracture treatment is to restore bone biomechanical
      properties and to allow restoring normal function at the affected site. If the
      new pharmacological approaches could be translated into clinical benefit and
      offered to patients with osteoporosis or other factors that put at risk the
      process of healing (subjects with severe loss of substance or fractures at high
      risk of complications), they could represent a valuable aid in the treatment of
      fractures.

PMID- 22461165
TI  - Pulsed electromagnetic fields and low intensity pulsed ultrasound in bone tissue.
AB  - The use of physical stimuli to modulate osteogenetic response and favour fracture
      healing has been the subject of research for many years now. Currently, 78% of
      hospitals in the USA provide this treatment at 3 months from the trauma.In
      literature, the findings of many clinical studies agree in confirming that
      biophysical stimuli are able to lead to healing in 75-85% of patients with
      nonunions. Prospective, randomized and double-blind studies show that by
      employing biophysical stimuli the time needed for a fresh fracture to heal can be
      reduced "on average" by 25-38%. The treatment is suggested for healing of fresh
      fractures that are characterized as "risk fractures", fractures that can evolve
      in nonunions and that amount to 20% of all the fractures; this justifies the use
      of biophysical stimuli, with a favourable cost-benefit ratio.Current orthopaedics
      reviews the different modalities of biophysical treatment in search of solutions
      most adequate to the pathology, the characteristics of the fracture and those of
      the patient. It is up to the orthopaedist to assess whether the biomechanical
      conditions of stability of the fracture site are such as not to jeopardize the
      osteogenetic process. International clinical experience shows that success in
      biophysical therapy for bone regeneration depends on certain principal factors:
      suitable indication, efficacy of the device employed, method of stimulation and -
      of crucial importance - patient compliance. If these principles are kept in mind,
      the percentage of success of union, obtained with biophysical stimulation,
      exceeds 90%.

PMID- 22461166
TI  - Bone healing induced by ESWT.
AB  - It has been at least two decades since the introduction of Extracorporeal Shock
      Wave Treatment (ESWT) for the treatment of non-unions; despite conflicting
      opinions in the literature, it is recently achieving good results also in acute
      fractures. This paper reports Authors' clinical experience with electromagnetic
      shock-waves in the treatment of delayed unions and fresh fractures. Nonunion
      cases experienced remarkable successful results at an average of 8-10 weeks after
      ESWT; high success rate is been also found for the acute fractures. It can be
      concluded that this therapy constitutes an important aid in treatment of non
      unions and can be useful also in fresh bone fractures.

PMID- 22461167
TI  - Play and players in bone fracture healing match.
AB  - Bone fractured healing is a specialized wound-healing response that leads to
      regeneration without scar restoring its own ability of mechanical loading. The
      four stage classification of fracture healing process, by John Hunter, is still
      the frame in which the new biological and molecular findings settle in.Nowadays
      the fracture healing is pictured like a playground where growth and
      differentiation factors, hormones, cytokines, and extracellular matrix play with
      bone and cartilage forming primary cells and muscle mesenchymal cells in a well
      orchestrated series of biological events. The ongoing knowledge of cellular and
      molecular interactions between blood vessels and bone cells shows great promise
      to enhance fracture management and the unsuccessfull process of bone healing.

PMID- 22461168
TI  - Effects of the SERM raloxifene on calcium and phosphate metabolism in healthy
      middle-aged men.
AB  - Background. Sex hormones are important regulators of calcium and phosphate
      homeostasis. Estradiol appears to be a major determinant of bone health in the
      male gender. However, physiological effects of estrogens on calcium and phosphate
      homeostatic fluxes in men are still poorly understood.Objective. We investigated
      the influence of 6 weeks of the SERM raloxifene, an estrogen agonist in bone, but
      devoid of feminizing actions, on calcium and phosphate metabolism in healthy
      middle-aged men.Design. In a double-blind, randomized, placebo-controled, cross
      over study, we evaluated the influence of 120 mg/day of raloxifene on
      calciotropic hormones levels, renal tubular reabsorption of calcium and
      phosphate, and intestinal calcium absorption, as assessed by the calciuric
      response to an oral calcium load.Results. As compared to the placebo period,
      raloxifene treatment decreased the response to an oral calcium load, together
      with a decrease in 1,25(OH)(2)D(3) and in IGF-I serum levels. Maximal renal
      tubular phosphate reabsorption was decreased in raloxifene-treated men following
      the calcium load. The renal handling of calcium was not changed.Conclusion. These
      results are compatible with the hypothesis that raloxifene is associated with
      lower IGF-I and 1,25(OH)(2)D(3) levels, with consequently reduced intestinal
      calcium absorption capacity.

PMID- 22461169
TI  - Biological effects of various regimes of 25-hydroxyvitamin D3 (calcidiol)
      administration on bone mineral metabolism in postmenopausal women.
AB  - Introduction. It is evident from several studies that vitamin D inadequacy is
      widespread among women with osteoporosis across all continents regardless of
      season or latitude, with similar prevalence in patients treated for osteoporosis
      and in untreated women. These results underscore a need to improve physician and
      patient awareness of the importance of adequate vitamin D supplementation in
      postmenopausal women with osteoporosis.Materials and Methods. As the daily
      administration of vitamin D combined with 1 gr calcium is hampered by an
      insufficient patient adherence, we performed a longitudinal study in 90 randomly
      recruited postmenopausal women aged 65-75 years with inadequate calcium intake
      and circulating levels of 25-hydroxyvitamin D3 (lower than 30 ng/mL). The
      prevalence of secondary hyperparathyroidism (parathyroid hormone > 65 pg/mL) was
      36% in the all population. The possible repercussion of oral single weekly or
      monthly calcidiol administration on phospho-calcium metabolism was observed after
      three months treatment (from April through July) with 500 mg calcium daily and
      with three different therapeutic regimens of calcidiol (Group I: 25 drops weekly;
      Group II: 50 drops monthly; and Group III: 100 drops monthly). The general
      baseline characteristics of the three groups were superimposable. We measured
      fasting morning serum 25-hydroxyvitamin D3, parathyroid hormone, calcium,
      phosphate, bone alkaline phosphatase, urinary deoxypyridinoline, and 24hr
      calcium, - phosphate, and - creatinine.Results. The adherence to the weekly
      calcidiol treatment was over 80% in 90% of the patients. All three therapeutic
      regimens of calcidiol led to normalization of 25-hydroxyvitamin D3 after 3
      months, yet with a significantly higher potency (P >0.01) of regimens I and III,
      when compared to Group II. Also the decrease of circulating levels of parathyroid
      hormone was significantly higher (P < 0.001) in Groups I and III versus Group II.
      No biochemically and clinically relevant adverse effects were observed at the end
      of the 90-day follow-up.ConclusionsIn postmenopausal women with inadequate
      circulating levels of 25-hydroxyvitamin D3, calcium and pulsed calcidiol
      supplementation normalized 25-hydroxyvitamin D3 levels and reduced circulating
      parathyroid hormone levels.

PMID- 22461170
TI  - Patient satisfaction in otolaryngology: Can academic institutions compete?
AB  - OBJECTIVES: Public reporting and transparency of patient experience is an
      emerging national healthcare priority. The objectives of this report are to
      describe patient satisfaction scores in ambulatory otolaryngology and examine the
      association of teaching status across multiple service domains. STUDY DESIGN:
      Cross-sectional patient-level analysis of Press Ganey outpatient medical practice
      surveys completed by otolaryngology patients in fiscal year 2010. METHODS: The
      survey contains 29 Likert-scaled items that comprise an overall score and scores
      in six service domains: access, visit, nursing, care provider, personal issues,
      and assessment. The item "likelihood-to-recommend practice" was measured as an
      indicator of patient loyalty. Surveys were grouped according to teaching or
      nonteaching setting. Mean scores were compared by Kruskal-Wallis rank test for
      nonparametric data with Bonferroni's correction for multiple comparisons. A
      dichotomous variable (ALL-5s) was created to measure percentages of surveys with
      highest scores in each domain. Multivariate logistic regression adjusting for
      sex, age, geographical region, urban-rural status, and first visit was performed
      to evaluate the association of teaching status with ALL-5s in each domain.
      Pearson correlation (r) was used to evaluate correlation of individual survey
      items to the "likelihood-to-recommend practice" question. RESULTS: A total of
      36,089 surveys were included, of which 16,057 (44%) were from a teaching setting.
      The mean age of respondents was 54.1 years (range, 0-90 years), and 52.7% were
      female. Patients seen in the teaching setting had lower mean scores overall and
      in domains of access, visit, and personal issues (P = .004) but had higher mean
      scores for likelihood-to-recommend practice (P = .007). No differences were
      identified between groups in domains of nursing, care provider, and assessment.
      Multivariate analysis of association of teaching setting with ALL-5s demonstrated
      that patients in a teaching setting were more likely to have the highest scores
      (ALL-5s) in the domain of nursing (OR, 1.09; 95% confidence interval [CI], 1.03
      1.16; P = .002) and for the loyalty question of "likelihood-to-recommend
      practice" (OR, 1.12; 95% CI, 1.05-1.19; P = .001), and less likely to have
      highest scores for the overall survey (OR, 0.88; 95% CI, 0.83-0.93; P < .001) and
      domains of access (OR, 0.89; 95% CI, 0.84-0.94;P < .001) and visit (OR, 0.89; 95%
      CI, 0.85-0.94; P < .001). No association was identified between teaching status
      and domains of care provider, personal issues, and assessment. Survey items
      correlated with likelihood-to-recommend practice were similar between groups.
      Items most closely correlated with loyalty were all within the care provider
      domain consisting of "likelihood-to-recommend care provider" (r = 0.839),
      "confidence in care provider" (r = 0.785), and "concern care provider showed" (r
      = 0.733; P < .001). Items least closely correlated were within the visit domain
      related to waiting room comfort (r = 0.467), registration speed (r = 0.447), and
      wait time (r = 0.432; P < .001). CONCLUSIONS: Otolaryngology patients evaluated
      in the teaching setting report lower patient satisfaction overall, primarily
      related to access to care and visit-specific processes; however, they are more
      likely to display loyalty and recommend their practice and care provider. The
      teaching setting does not influence care provider satisfaction scores. Because
      practice loyalty is most closely correlated to provider-specific behaviors,
      otolaryngologists may consider enhancement of provider-patient communication to
      improve patient satisfaction regardless of the practice setting. Academic
      otolaryngology practices should consider focusing on access systems and process
      improvement to enhance the overall patient experience.

PMID- 22461171
TI  - Preeclampsia: the role of tissue factor and tissue factor pathway inhibitor.
AB  - Preeclampsia (PE) is a multi-system disorder of human pregnancy, whose etiology
      remains poorly understood. Preeclamptic women are known to have an increased
      hypercoagulable state that result in excess fibrin deposition in several organs,
      which compromises their function. Tissue factor (TF) is the main physiological
      initiator of blood coagulation and its activity is regulated by a specific
      inhibitor known as Tissue factor pathway inhibitor (TFPI). Based on the important
      role of TF and TFPI in hemostasis, we hypothesize that their levels may change in
      the severe PE contributing to exacerbate hypercoagulable state. Some studies have
      assessed the balance between TF and TFPI in preeclamptic women, but results are
      inconsistent. Therefore, the aim of this study was to examine these
      inconsistencies and to assess TF and TFPI plasma levels in three groups of age
      matched women; pregnant with severe PE (n = 60), normotensive pregnant (n = 50)
      and normotensive non-pregnant women (n = 50). There was not significantly
      different among the three groups for TF plasma levels; severe PE women: 338.4
      pg/mL (248.1-457.6), normotensive pregnant women: 301.5 pg/mL (216.4-442.9) and
      normotensive non-pregnant women 393 pg/mL (310.3-522.9). TFPI plasma levels were
      higher in severe PE comparing to normotensive pregnant women and normotensive non
      pregnant women, 115.8 ng/mL (75-149.8); 80.3 ng/mL (59.6-99.7) and 74.5 ng/mL
      (47.1-98.0), respectively No difference was found between normotensive pregnant
      women and normotensive non-pregnant women. As for gestational age, a significant
      difference in TFPI levels was found between severe PE and normotensive pregnant
      women up to the 33rd week of pregnancy (p = 0.001), and severe PE and non
      pregnant women up to the 34th (p = 0.01). In summary, our results indicated that
      TF plasma levels did not vary in the studied groups, while TFPI plasma levels
      were significantly increased in severe PE compared to normotensive pregnant and
      normotensive non-pregnant women. So, our data do not explain the exacerbated
      hypercoagulability state observed in severe PE. Further studies evaluating genes
      expression, TF activity and antigen, total and free TFPI and TFPI-2, both in
      plasma and obstetric tissues, throughout the pregnancy in PE (mild and severe
      forms) are required.

PMID- 22461173
TI  - What controls the magnetic interaction in bis-MU-alkoxo Mn(III) dimers? A
      combined experimental and theoretical exploration.
AB  - The synthesis and magnetic characterisation of a series of bis-MU-alkoxide
      bridged Mn(III) dinuclear complexes of general formula [Mn(III)(2)(MU
      OR)(2)(biphen)(2)(ROH)(x)(L)(y)] (where R = Me, Et; H(2) biphen = 2,2'-biphenol
      and L = terminally bonded N-donor ligand) is described, doubling the literature
      basis set for this type of complex. Building on these findings we have
      categorised all known MU-OR bridged Mn(III) dinuclear complexes into one of three
      classifications with respect to their molecular structures. We have then employed
      DFT and MO calculations to assess all potential magneto-structural correlations
      for this class of compound in order to identify the structural requirements for
      constructing ferromagnetic family members. Our analysis indicates that the most
      influential parameter which governs the exchange interaction in this class of
      compounds is the relative orientation of the JT axes of the Mn(III)  atoms. A
      perpendicular orientation of the JT axes leads to a large ferromagnetic
      contribution to the exchange. These results also suggest that a large
      ferromagnetic interaction and a large anisotropy are unlikely to co-exist in such
      structural types.

PMID- 22461174
TI  - Electrochemical synthesis of a thiophene-containing cyclo[9]pyrrole.
AB  - A new member of the cyclo[n]pyrrole class of expanded porphyrins could be
      prepared from the corresponding thiophene-containing terpyrrole precursor through
      use of a mild electrochemical oxidative procedure. The isolated macrocycle,
      featuring nine heterocyclic subunits directly connected through their
      alpha,alpha'-positions, is the largest cyclo[n]pyrrole derivative reported to
      date (see figure).

PMID- 22461172
TI  - Ski inhibits TGF-beta/phospho-Smad3 signaling and accelerates hypertrophic
      differentiation in chondrocytes.
AB  - Since transforming growing factor-beta (TGF-beta)/Smad signaling inhibits
      chondrocyte maturation, endogenous negative regulators of TGF-beta signaling are
      likely also important regulators of the chondrocyte differentiation process. One
      such negative regulator, Ski, is an oncoprotein that is known to inhibit TGF
      beta/Smad3 signaling via its interaction with phospho-Smad3 and recruitment of
      histone deacetylases (HDACs) to the DNA binding complex. Based on this, we
      hypothesized that Ski inhibits TGF-beta signaling and accelerates maturation in
      chondrocytes via recruitment of HDACs to transcriptional complexes containing
      Smads. We tested this hypothesis in chick upper sternal chondrocytes (USCs),
      where gain and loss of Ski expression experiments were performed. Over-expression
      of Ski not only reversed the inhibitory effect of TGF-beta on the expression of
      hypertrophic marker genes such as type X collagen (colX) and osteocalcin, it
      induced these genes basally as well. Conversely, knockdown of Ski by RNA
      interference led to a reduction of colX and osteocalcin expression under basal
      conditions. Furthermore, Ski blocked TGF-beta induction of cyclinD1 and caused a
      basal up-regulation of Runx2, consistent with the observed acceleration of
      hypertrophy. Regarding mechanism, not only does Ski associate with phospho-Smad2
      and 3, but its association with phospho-Smad3 is required for recruitment of
      HDAC4 and 5. Implicating this recruitment of HDACs in the phenotypic effects of
      Ski in chondrocytes, the HDAC inhibitor SAHA reversed the up-regulation of colX
      and osteocalcin in Ski over-expressing cells. These results suggest that
      inhibition of TGF-beta signaling by Ski, which involves its association with
      phospho-Smad3 and recruitment of HDAC4 and 5, leads to accelerated chondrocyte
      differentiation.

PMID- 22461175
TI  - Insulin induces the correlation between renal blood flow and glomerular
      filtration rate in diabetes: implications for mechanisms causing hyperfiltration.
AB  - Glomerular filtration rate (GFR) and renal blood flow (RBF) are normally kept
      constant via renal autoregulation. However, early diabetes results in increased
      GFR and the potential mechanisms are debated. Tubuloglomerular feedback (TGF)
      inactivation, with concomitantly increased RBF, is proposed but challenged by the
      finding of glomerular hyperfiltration in diabetic adenosine A(1) receptor
      deficient mice, which lack TGF. Furthermore, we consistently find elevated GFR in
      diabetes with only minor changes in RBF. This may relate to the use of a lower
      streptozotocin dose, which produces a degree of hyperglycemia, which is
      manageable without supplemental suboptimal insulin administration, as has been
      used by other investigators. Therefore, we examined the relationship between RBF
      and GFR in diabetic rats with (diabetes + insulin) and without suboptimal insulin
      administration (untreated diabetes). As insulin can affect nitric oxide (NO)
      release, the role of NO was also investigated. GFR, RBF, and glomerular
      filtration pressures were measured. Dynamic RBF autoregulation was examined by
      transfer function analysis between arterial pressure and RBF. Both diabetic
      groups had increased GFR (+60-67%) and RBF (+20-23%) compared with controls.
      However, only the diabetes + insulin group displayed a correlation between GFR
      and RBF (R(2) = 0.81, P < 0.0001). Net filtration pressure was increased in
      untreated diabetes compared with both other groups. The difference between
      untreated and insulin-treated diabetic rats disappeared after administering
      N(omega)-nitro-l-arginine methyl ester to inhibit NO synthase and subsequent NO
      release. In conclusion, mechanisms causing diabetes-induced glomerular
      hyperfiltration are animal model-dependent. Supplemental insulin administration
      results in a RBF-dependent mechanism, whereas elevated GFR in untreated diabetes
      is mediated primarily by a tubular event. Insulin-induced NO release partially
      contributes to these differences.

PMID- 22461176
TI  - Peroxisome proliferator-activated receptor-gamma protects against vascular aging.
AB  - Vascular disease occurs commonly during aging. Carotid artery and cerebrovascular
      disease are major causes of stroke and contributors to dementia. Recent evidence
      suggests that peroxisome proliferator-activated receptor-gamma (PPARgamma) may
      play a protective role in the vasculature, but the potential importance of
      PPARgamma in vascular aging is unknown. To examine the hypothesis that PPARgamma
      normally protects against vascular aging, we studied heterozygous knockin mice
      expressing a human dominant-negative mutation in PPARgamma (P465L, designated
      L/+). Endothelial dysfunction, a major contributor to vascular disease, was
      studied using carotid arteries from adult (8 +/- 1 mo) and old (24 +/- 1 mo) L/+
      mice and wild-type littermates. In arteries from wild-type mice, responses to the
      endothelium-dependent agonist ACh were similar in adult and old wild-type mice
      but were reduced by ~50% in old L/+ mice (n = 7-10, P < 0.05). Impaired responses
      in arteries from old L/+ mice were restored to normal by a scavenger of
      superoxide. Relaxation of arteries to nitroprusside (an NO donor) was similar in
      all groups. Contraction of arteries to U46619 was not affected by age or
      genotype, while maximal responses to endothelin-1 were reduced with age in both
      wild-type and L/+ mice. Vascular expression (mRNA) of the catalytic component of
      NADPH oxidase (Nox2) was not altered in wild-type mice but was increased
      significantly in old L/+ mice. These findings provide the first evidence that
      interference with PPARgamma function accelerates vascular aging, suggesting a
      novel role for PPARgamma in protecting against age-induced oxidative stress and
      endothelial dysfunction.

PMID- 22461177
TI  - Activating autoantibodies to the angiotensin II type I receptor play an important
      role in mediating hypertension in response to adoptive transfer of CD4+ T
      lymphocytes from placental ischemic rats.
AB  - Hypertension in rats with chronic placental ischemia (reduced uterine perfusion
      pressure, RUPP) is associated with elevated inflammatory cytokines, agonistic
      autoantibodies to the angiotensin II type I receptor (AT1-AA) and CD4(+) T cells;
      all of which are elevated in preclamptic women. Additionally, we have shown that
      adoptive transfer of RUPP CD4(+) T cells increases blood pressure, inflammatory
      cytokines, and sFlt-1. The objective of this study was to determine the long-term
      effects of RUPP CD4(+) T cells on AT1-AA, renal and systemic hemodynamics in
      pregnant rats. To answer this question CD4(+) T splenocytes were magnetically
      isolated on day 19 of gestation from control RUPP and normal pregnant (NP) rats
      and injected into a new group of NP rats at day 13 of gestation. On day 19 of
      gestation mean arterial pressure (MAP) and renal function (glomerular filtration
      rates, GFR) were analyzed and serum collected for AT1-AA analysis. To determine a
      role for AT1-AA to mediate RUPP CD4(+) T cell-induced blood pressure increases,
      MAP was analyzed in a second group of rats treated with AT1 receptor blockade
      losartan (10 mg.kg(-1).day(-1)) and in a third group of rats treated with
      rituximab, a B cell-depleting agent (250 mg/kg) we have shown previously to
      decrease AT1-AA production in RUPP rats. MAP increased from 101 +/- 2 mmHg NP to
      126 +/- 2 mmHg in RUPP rats (P < 0.001) and to 123 +/- 1 mmHg in NP rats injected
      with RUPP CD4(+) T cells (NP+RUPP CD4(+)T cells) (P < 0.001). Furthermore, GFR
      decreased from 2.2 ml/min (n = 7) in NP rats to 1.0 ml/min (n = 5) NP+RUPP
      CD4(+)T cell. Circulating AT1-AA increased from 0.22 +/- 0.1 units in NP rats to
      13 +/- 0.7 (P < 0.001) units in NP+RUPP CD4(+)T cell-treated rats but decreased
      to 8.34 +/- 1 beats/min in NP+RUPP CD4(+) T cells chronically treated with
      rituximab. Hypertension in NP+RUPP CD4(+)T cell group was attenuated by losartan
      (102 +/- 4 mmHg) and with B cell depletion (101 +/- 5 mmHg). Therefore, we
      conclude that one mechanism of hypertension in response to CD4(+) T lymphocytes
      activated during placental ischemia is via AT1 receptor activation, potentially
      via AT1-AA during pregnancy.

PMID- 22461178
TI  - Inspiratory muscle fatigue increases sympathetic vasomotor outflow and blood
      pressure during submaximal exercise.
AB  - The purpose of this study was to elucidate the influence of inspiratory muscle
      fatigue on muscle sympathetic nerve activity (MSNA) and blood pressure (BP)
      response during submaximal exercise. We hypothesized that inspiratory muscle
      fatigue would elicit increases in sympathetic vasoconstrictor outflow and BP
      during dynamic leg exercise. The subjects carried out four submaximal exercise
      tests: two were maximal inspiratory pressure (PI(max)) tests and two were MSNA
      tests. In the PI(max) tests, the subjects performed two 10-min exercises at 40%
      peak oxygen uptake using a cycle ergometer in a semirecumbent position
      [spontaneous breathing for 5 min and with or without inspiratory resistive
      breathing for 5 min (breathing frequency: 60 breaths/min, inspiratory and
      expiratory times were each set at 0.5 s)]. Before and immediately after exercise,
      PI(max) was estimated. In MSNA tests, the subjects performed two 15-min exercises
      (spontaneous breathing for 5 min, with or without inspiratory resistive breathing
      for 5 min, and spontaneous breathing for 5 min). MSNA was recorded via
      microneurography of the right median nerve at the elbow. PI(max) decreased
      following exercise with resistive breathing, whereas no change was found without
      resistance. The time-dependent increase in MSNA burst frequency (BF) appeared
      during exercise with inspiratory resistive breathing, accompanied by an
      augmentation of diastolic BP (DBP) (with resistance: MSNA, BF +83.4%; DBP,
      +23.8%; without resistance: MSNA BF, +19.2%; DBP, -0.4%, from spontaneous
      breathing during exercise). These results suggest that inspiratory muscle fatigue
      induces increases in muscle sympathetic vasomotor outflow and BP during dynamic
      leg exercise at mild intensity.

PMID- 22461180
TI  - A worldview of the professional experiences and training needs of pediatric
      psycho-oncologists.
AB  - BACKGROUND: Thirty years after the origin of the field of psycho-oncology,
      limited data exist about the work practices of professionals providing
      psychosocial care to children with cancer and their families. METHOD: A survey
      was designed to assess training, work environment, theoretical orientation,
      services provided, subspecialty areas or areas of special interest,
      satisfactions, challenges, and continuing education needs of pediatric psycho
      oncologists. Members of national and international psycho-oncology organizations
      were invited to participate in the web-based survey. RESULTS: Seven hundred
      eighty-six professionals from 63 countries responded. The sample consisted mostly
      of psychologists (41%), physicians (20%), and social workers (14%). Approximately
      half of the participants worked in a designated psycho-oncology unit.
      Psychologists and social workers provided the majority of psychosocial services.
      Individual sessions with parents were most common (42%), followed by sessions
      with children (41%), survivors (36%), families (31%), and siblings (25%).
      Therapies provided include cognitive behavioral therapy (50%), relaxation (43%),
      psychodynamic psychotherapy (27%), play therapy (26%), and imagery (23%). Two
      thirds reported having appropriate supervision, 37% were conducting research, and
      only half felt their salary was appropriate. Differences in therapeutic
      modalities were found by country. Clinicians desire training on clinical
      interventions, improving communication with medical staff, research, and ethics.
      CONCLUSIONS: An international cohort of clinicians providing pediatric psycho
      oncology services perform a wide variety of tasks, use a range of therapeutic
      approaches, and report considerable work satisfaction. Problem areas include
      professional inter-relations, inadequate supervision, and need for additional
      specialized training. Opportunity exists for global collaboration in pediatric
      psycho-oncology research and practices to enhance clinical effectiveness and
      reduce professional isolation.

PMID- 22461179
TI  - Systems genetic analysis of multivariate response to iron deficiency in mice.
AB  - The aim of this study was to identify genes that influence iron regulation under
      varying dietary iron availability. Male and female mice from 20+ BXD recombinant
      inbred strains were fed iron-poor or iron-adequate diets from weaning until 4 mo
      of age. At death, the spleen, liver, and blood were harvested for the measurement
      of hemoglobin, hematocrit, total iron binding capacity, transferrin saturation,
      and liver, spleen and plasma iron concentration. For each measure and diet, we
      found large, strain-related variability. A principal-components analysis (PCA)
      was performed on the strain means for the seven parameters under each dietary
      condition for each sex, followed by quantitative trait loci (QTL) analysis on the
      factors. Compared with the iron-adequate diet, iron deficiency altered the factor
      structure of the principal components. QTL analysis, combined with PosMed (a
      candidate gene searching system) published gene expression data and literature
      citations, identified seven candidate genes, Ptprd, Mdm1, Picalm, lip1, Tcerg1,
      Skp2, and Frzb based on PCA factor, diet, and sex. Expression of each of these is
      cis-regulated, significantly correlated with the corresponding PCA factor, and
      previously reported to regulate iron, directly or indirectly. We propose that
      polymorphisms in multiple genes underlie individual differences in iron
      regulation, especially in response to dietary iron challenge. This research shows
      that iron management is a highly complex trait, influenced by multiple genes.
      Systems genetics analysis of iron homeostasis holds promise for developing new
      methods for prevention and treatment of iron deficiency anemia and related
      diseases.

PMID- 22461181
TI  - Functional genetic variation at the NRGN gene and schizophrenia: evidence from a
      gene-based case-control study and gene expression analysis.
AB  - Genome-wide association and follow-up studies have reported an association
      between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We
      investigated the association of five linkage disequilibrium-tagging SNPs and
      haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of
      2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809
      is the most strongly associated variant for schizophrenia in the vicinity of the
      NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was
      associated with schizophrenia (global P = 0.0042). The frequencies of the TG and
      TA haplotypes of rs12807809-rs12278912 in patients were higher (OR = 1.14, P =
      0.0019) and lower (OR = 0.85, P = 0.0053), respectively, than in the controls. We
      did not detect any evidence of association of schizophrenia with any SNPs;
      however, two nominal associations of rs12278912 (OR = 1.10, P = 0.057) and
      rs2075713 (OR = 1.10, P = 0.057) were observed. Furthermore, we detected an
      association between the rs12807809-rs12278912 haplotype and NRGN expression in
      immortalized lymphoblasts derived from 45 HapMap JPT subjects (z = 2.69, P =
      0.007) and confirmed the association in immortalized lymphoblasts derived from 42
      patients with schizophrenia and 44 healthy controls (z = 3.09, P = 0.002). The
      expression of the high-risk TG haplotype was significantly lower than the
      protective TA haplotype. The expression was lower in patients with schizophrenia
      than in controls; however, this difference was not statistically significant.
      This study provides further evidence of the association of the NRGN gene with
      schizophrenia, and our results suggest that there is a link between the TG
      haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of
      developing schizophrenia.

PMID- 22461182
TI  - Subjective uncertainty and limbic hyperactivation in obsessive-compulsive
      disorder.
AB  - Obsessive-compulsive disorder (OCD) is often associated with pathological
      uncertainty regarding whether an action has been performed correctly or whether a
      bad outcome will occur, leading to compulsive "evidence gathering" behaviors
      aimed at reducing uncertainty. The current study used event-related functional
      magnetic resonance imaging to investigate neural functioning in OCD patients and
      controls as subjective certainty was rated in response to sequential pieces of
      evidence for a decision. Uncertainty was experimentally manipulated so that some
      decisions were associated with no "objective" uncertainty (all observed evidence
      pointed to one correct choice), whereas other decisions contained calculable but
      varying levels of objective uncertainty based on displayed probabilities. Results
      indicated that OCD patients differed from controls on decisions that contained no
      objective uncertainty, such that patients rated themselves as more uncertain.
      Patients also showed greater activation in a network of brain regions previously
      associated with internally-focused thought and valuation including ventromedial
      prefrontal cortex, parahippocampus, middle temporal cortex, as well as amygdala
      and orbitofrontal cortex/ventral anterior insula. In the patient group, a
      significantly greater number of positive intersubject correlations were found
      among several of these brain regions, suggesting that this network is more
      interconnected in patients. OCD patients did not differ from controls on
      decisions where task parameters led to uncertainty. These results indicate that
      OCD is associated with hyperactivation in a network of limbic/paralimbic brain
      regions when making decisions, which may contribute to the greater subjective
      experience of doubt that characterizes the disorder.

PMID- 22461183
TI  - Moxibustion for the treatment of osteoarthritis: a systematic review and meta
      analysis.
AB  - The aim of this review was to summarise and critically evaluate the evidence from
      randomised clinical trials (RCTs) of moxibustion as a treatment for patients with
      osteoarthritis (OA). Twelve databases were searched from their inception through
      July 2011. RCTs were considered whether they assessed any type of clinical
      outcome from moxibustion therapy for patients with OA localised to any joints.
      Two reviewers independently performed the selection of studies, data abstraction
      and validations. The risk of bias was assessed using the Cochrane criteria. Eight
      RCTs met our inclusion criteria, and most of them had significant methodological
      weaknesses. Six RCTs tested the effects of moxibustion against conventional oral
      drug therapies in patients with knee OA (KOA). Meta-analysis showed favourable
      effects of moxibustion on the response rate (n = 540; RR, 1.09; 95 % CI 1.03
      1.17; P = 0.005; heterogeneity: chi(2) = 5.48, P = 0.36, I (2) = 9 %). Two RCTs
      tested the effects of moxibustion on response rate after 2 months. The meta
      analysis failed to show favourable effects of moxibustion (n = 180; RR, 1.10; 95
      % CI 0.97-1.24; P = 0.13; heterogeneity: chi(2) = 0.03, P = 0.87, I (2) = 0 %).
      In conclusion, consistent results show that moxibustion may be effective in
      symptom management in patients with KOA. However, because of the number of
      eligible RCTs and the high risk of bias in the assessment of the available RCTs,
      the evidence supporting this conclusion is limited.

PMID- 22461184
TI  - Causes and predictors of death in Brazilian lupus patients.
AB  - The objective of this study is to determine the causes and predictors of death in
      systemic lupus erythematosus (SLE) patients. Causes of death were defined based
      on death certificates, medical records, and information collected from doctors
      and relatives. Possible variables predicting mortality were assessed by Kaplan
      Meier and Cox regression methods. The multivariate model was validated using the
      bootstrap method, and the hazard ratios were adjusted according to the shrinkage
      coefficient. One hundred eighty-one patients were included, and two patients were
      lost to follow-up. The median (IR) age at T (0) and disease duration of the 179
      patients were 26.7 (21.8-34.6) and 8.2 (4.3-12.4) years, respectively. After a
      median (IR) follow-up of 3.3 (3.1-3.5) years, 13 (7.3 %) patients died due to end
      organ failure (5), infection (5), disease activity (1), and atherosclerotic
      cardiovascular disease (CVD) (1). The cause of mesenteric ischemia in one patient
      could not be determined. Predictors of mortality collected at T(0) were the
      following: nephritis, chronic kidney disease, antiphospholipid syndrome (APS),
      higher modified SLEDAI-2k, higher damage index score, intravenous
      cyclophosphamide use, higher daily dose of prednisone, and higher systolic blood
      pressure. Independent predictors of mortality were higher damage index score (HR:
      1.40; 95 % CI: 1.08-1.82), cyclophosphamide use (HR: 3.80; 95 % CI: 1.13-12.77),
      and APS diagnosis (HR: 3.82; 95 % CI: 1.07-13.59). This paper presents a high
      frequency of late mortality in lupus patients due to the SLE itself and
      infection. This result is not in agreement with the initial proposed bimodal
      pattern of lupus mortality, nor is it in agreement with the high frequency of CVD
      as a cause of death in developed countries. The most important predictors of
      death were related to the lupus itself.

PMID- 22461185
TI  - Circulating angiopoietin and Tie-2 levels in systemic sclerosis.
AB  - To determine the potential effects of angiopoietins Ang-1 and Ang-2 and their
      receptor Tie-2 in patients with systemic sclerosis (SSc). Twenty-six patients
      with limited SSc (l-SSc) and fourteen patients with diffuse SSc (d-SSc) were
      evaluated and compared to age-matched controls. Plasma levels of soluble sAng-1,
      sAng-2, sTie-2, vascular endothelial growth factor (VEGF), placental growth
      factor (PlGF) and endostatin were measured. Associations between these factors
      and clinical parameters were assessed. Levels of circulating factors and the
      ratios sAng-2/sAng-1 and sAng-2/sTie-2 were not different between l-SSc and d-SSc
      cases but were collectively higher compared to their controls: sAng-1 (p =
      0.0108); sAng-2 (p < 0.0001); sTie-2 (p < 0.0001); endostatin (p < 0.0001), PlGF
      (p < 0.0001); VEGF (p = 0.0006); sAng-2/sAng-1 (p < 0.0001); sAng-2/sTie-2 (p <
      0.0001). Concerning significant correlations among the angiopoietins and Tie-2,
      sAng-2 associated with sTie-2 (Spearman r = 0.47, p = 0.0155) in l-SSc only. sAng
      1 did not show statistically significant correlations with any of the clinical
      variables, but sAng-2 did between PAP (r = 0.51, p = 0.0148) and predicted DLCO
      (r = -0.31, p = 0.0242) in l-SSc cases. sTie-2 negatively correlated with disease
      duration in l-SSc (r = -0.55, p = 0.0049). The sAng-2/sTie-2 ratio shows a
      positive association with disease activity in both l-SSc (r = 0.50, p = 0.0547)
      and d-SSc (r = 0.60, p = 0.0317). Levels of sAng-1, sAng-2 and sTie-2 are higher
      in SSc cases suggesting a pro-inflammatory state in an active endothelium. The
      near doubling of the sAng-2/sTie-2 ratio in SSc cases compared to controls
      suggests a shift toward vascular regression and angiostasis perhaps caused by Ang
      2 blocking the action of Tie-2.

PMID- 22461186
TI  - Serum levels of selected chemokines in systemic lupus erythematosus patients.
AB  - Chemokines promote leukocyte traffic into the site of inflammation. Serum levels
      of monocyte chemotactic protein 1 (MCP-1), stromal cell-derived factor-1 (SDF-1),
      interferon-gamma-inducible protein 10 (IP-10), and interleukin-8 (IL-8) were
      evaluated in 48 treated women with systemic lupus erythematosus (SLE) and mild-to
      moderate disease severity. The results were compared between the whole SLE group
      and the control (29 women). The relationships between chemokines, their
      concentrations, and peripheral blood leukocyte count and between the chemokines
      and individual leukocyte populations (polymorphonuclear leukocytes-PMNs,
      lymphocytes-Ls, monocytes-Ms, eosinophils) counts were determined. The
      relationships between the analyzed chemokines were also determined in the
      control. SLE subjects had significantly higher MCP-1, SDF-1, IP-10, and lower IL
      8 concentrations compared to the control. Moderate, positive correlations between
      MCP-1/SDF-1, SDF-1/IP-10 and a negative correlation between MCP-1/IL8 were
      observed in the patient group. Moderate, negative correlations were found between
      SDF-1/total leukocyte count, SDF-1/absolute number of PMNs as well as between IP
      10/total leukocyte count, IP-10/absolute PMNs, Ls, and Ms counts in peripheral
      blood of SLE group. We suggest that the obtained results and correlations
      observed between the examined parameters might be used to monitor SLE course and
      progression. However, further randomized clinical studies should be carried out
      on in untreated and treated patients with SLE.

PMID- 22461187
TI  - Low prevalence of work disability in early inflammatory arthritis (EIA) and early
      rheumatoid arthritis at enrollment into a multi-site registry: results from the
      catch cohort.
AB  - We determined the prevalence of work disability in early rheumatoid arthritis
      (ERA) and undifferentiated early inflammatory arthritis (EIA) patients at first
      enrollment into the Canadian Early Arthritis Cohort (CATCH) who met the 2010 ACR
      criteria versus those not meeting criteria, to determine the impact of meeting
      new criteria on work disability status. Data at first visit into the cohort were
      analyzed. Descriptive statistics and logistic regression analyses were performed
      to investigate the association of other variables in our database with work
      disability. 1,487 patients were enrolled in the CATCH study, a multi-site
      observational, prospective cohort of patients with EIA. 934 patients were
      excluded (505 based on missing criteria for ACR 2010 classification, as anti-CCP
      was absent, and 429 were not working for other reasons). Of the 553 patients
      included, 71 % were female with mean disease duration of 6.4 months. 524 (94.8 %)
      were employed while 29 (5.2 %) reported work disability at first visit. There
      were no differences between those meeting 2010 ACR criteria versus those who did
      not. Baseline characteristics associated with work disability were male gender,
      age, education, income, HAQ, and positive RF status. The mean HAQ score in work
      disabled patients was 1.4 versus 0.9 in those who were working (p < 0.001).
      Disease activity score (DAS28) was not associated with work disability (p =
      0.069), nor was tender joint count, swollen joint count, anti-CCP, patient global
      assessment, or SF-12v2. In the regression model, work disability was associated
      with lower income levels (p = 0.01) and worse HAQ scores (OR 2.33; p = 0.001),
      but not significantly associated with male gender (p = 0.08), older age (>50
      years; p = 0.3), lower education (p = 0.3) or RF positivity (p = 0.6). We found
      rates of work disability to be low at entry into this EIA cohort compared to
      previous studies. There may be potential for intervention in ERA to prevent the
      development of work disability.

PMID- 22461189
TI  - Emeritus O. Univ. Prof. Dr. Med. Univ. Walter Thiel (1919-2012).

PMID- 22461188
TI  - Role of glucosamine in the treatment for osteoarthritis.
AB  - Over the last 20 years, several studies have investigated the ability of
      glucosamine sulfate to improve the symptoms (pain and function) and to delay the
      structural progression of osteoarthritis. There is now a large, convergent body
      of evidence that glucosamine sulfate, given at a daily oral dose of 1,500 mg, is
      able to significantly reduce the symptoms of osteoarthritis in the lower limbs.
      This dose of glucosamine sulfate has also been shown, in two independent studies,
      to prevent the joint space narrowing observed at the femorotibial compartment in
      patients with mild-to-moderate knee osteoarthritis. This effect also translated
      into a 50 % reduction in the incidence of osteoarthritis-related surgery of the
      lower limbs during a 5-year period following the withdrawal of the treatment.
      Some discrepancies have been described between the results of studies performed
      with a patent-protected formulation of glucosamine sulfate distributed as a drug
      and those having used glucosamine preparations purchased from global suppliers,
      packaged, and sold over-the-counter as nutritional supplements.

PMID- 22461190
TI  - Eliminating the scattering ambiguity in multifocal, multimodal, multiphoton
      imaging systems.
AB  - In this work we present how to entirely remove the scattering ambiguity present
      in existing multiphoton multifocal systems. This is achieved through the
      development and implementation of single-element detection systems that
      incorporate high-speed photon-counting electronics. These systems can be used to
      image entire volumes in the time it takes to perform a single transverse scan
      (four depths simultaneously at a rate of 30 Hz). In addition, this capability is
      further exploited to accomplish single-element detection of multiple modalities
      (two photon excited fluorescence and second harmonic generation) and to perform
      efficient image deconvolution. Finally, we demonstrate a new system that promises
      to significantly simplify this promising technology.

PMID- 22461191
TI  - Azobenzenes in a new light-switching in vivo.
AB  - Two bands make light work: since the isomerization of azobenzenes is usually
      induced by UV light, its application is limited in living systems. A new
      azobenzene switch now operates entirely in the visible range. The new design is
      based on the introduction of OMe groups in the ortho positions, which splits the
      n-pi* transition into two absorption bands. The two isomeric forms can be
      obtained with more than 80 % enrichment from the respective photostationary
      state.

PMID- 22461192
TI  - Tetrahedral silicon balloon for endoscopic skull base reconstruction.

PMID- 22461193
TI  - Expression of A20 is reduced in pancreatic cancer tissues.
AB  - A20 protein plays essential roles in tumorigenesis, but its value for diagnosis
      of pancreatic cancer remains unclear. Our aim was to determine whether A20 is a
      potential biomarker for the diagnosis of pancreatic cancer. The pancreatic cancer
      tissue microarray contained pancreatic cancer tissues (n = 40) and normal tissues
      (n = 10) was immunohistochemically assessed for A20 expression. The association
      of A20 expression with the tumor grade, lymph node metastasis, age and gender in
      pancreatic cancer patients were estimated by ANOVA. Stronger staining of A20 was
      observed in the normal tissues compared with that in the pancreatic cancer
      tissues (P = 0.003). ANOVA analysis showed that the A20 expression was not deeply
      associated with tumor grade, gender, age or TNM stages. The results implied that
      low A20 expression is significantly associated with the pancreatic cancer
      behavior, but is not the sole determinant of pancreatic cancer progression.

PMID- 22461194
TI  - Colloidal carbon stimulation of Kupffer cells triggers Nrf2 activation in the
      isolated perfused rat liver.
AB  - Activation of transcription factor Nrf2 was investigated in the isolated perfused
      rat liver infused with 0.5 mg of colloidal carbon (CC)/ml for 5-15 min to
      stimulated Kupffer cell function. Infusion of CC enhanced liver O(2) consumption
      over basal levels, with a time-dependent increase in CC-induced O(2) uptake, at
      constant rates of CC phagocytosis by Kupffer cells, as assessed histologically,
      and adequate viability conditions of the livers, as shown by the marginal (0.34
      %) total sinusoidal lactate dehydrogenase (LDH) efflux over intrahepatic LDH
      activity. Under these conditions, cytosolic protein levels of Nrf2 (Western blot)
      and inhibitor of Nrf2 Keap1 progressively declined by CC infusion, those of
      nuclear Nrf2 increased, leading to enhancement in the nuclear/cytosolic Nrf2
      ratios. It is concluded that the respiratory burst of CC-stimulated Kupffer cells
      triggers Nrf2 activation in the perfused liver, a response that may afford
      cellular protection under pro-oxidant conditions underlying Kupffer cell
      stimulation.

PMID- 22461195
TI  - Structural analysis of human placental stem and terminal villi from normal and
      idiopathic growth restricted pregnancies.
AB  - Studying in detail different histomorphological and pathological findings in
      placental stem and terminal villi of appropriate for gestational age (AGA) and
      idiopathic intrauterine growth restricted (IUGR) fetuses, then analyzing their
      correlation to the neonatal birth weight and to the some morphological features
      of the placenta. Fifty full-term human placentae of idiopathic IUGR and 25 of AGA
      pregnancies were processed for haematoxylin and eosin staining and evaluated by
      light microscope aided with Image Analyzer. The mean number of stem villous
      arteries, and the mean number of terminal villous capillaries per field are
      significantly lower in idiopathic IUGR group (4.63 +/- 0.46, 47.09 +/- 4.44,
      respectively) than in AGA group (12.36 +/- 0.61, 73.35 +/- 5.13, respectively) (p
      = 0.001). Both AGA and idiopathic IUGR placentae share the presence of many
      pathological features: (1) narrowing of stem villous arteries appears in 38 (76
      %) of IUGR cases and in 9 (36 %) of AGA cases with significant difference between
      groups (p = 0.001); (2) cellular infiltration (villitis) of the stem villi is
      significantly higher in IUGR cases [24 (48 %)] than in AGA cases [2 (8 %)] (p =
      0.001). The study shows significant correlation between the birth weight and
      different pathologic features in the stem villi as arterial number (r = 0.494; p
      = 0.000), arterial narrowing (r = 0.283, p = 0.004), degenerative changes (r =
      0.331, p = 0.001) and villitis (r = 0.275, p = 0.005). There is also significant
      correlation between neonatal birth weight and terminal villous capillary number
      (r = 0.281, p = 0.001) but no significant correlation is found between the birth
      weight and terminal villous fibrotic changes (r = -0.098, p = 0.318).
      Histomorphological and pathological changes in the stem villi could explore the
      cause of idiopathic IUGR. Stem villous arterial number, arterial narrowing,
      degeneration and villitis could be underlying mechanisms. Further researches on
      the hormonal and cytokine level should be undertaken to demonstrate the
      precipitating factors of these changes and the possible preventing measures.

PMID- 22461196
TI  - Detailed analysis of the delta-crystallin mRNA-expressing region in early
      development of the chick pituitary gland.
AB  - Although delta-crystallin (delta-crys), also known as lens protein, is
      transiently expressed in Rathke's pouch (RP) of the chick embryo, detailed
      temporal and spatial expression patterns have been obscure. In this study, to
      understand the relationship between the delta-crys mRNA-expressing region and RP
      formation, we examined the embryonic expression pattern of delta-crys mRNA in the
      primordium of the adenohypophysis. delta-crys mRNA expression was initially found
      at stage 15 anterior to the foregut and posterior to the invaginated oral
      ectoderm. After RP formation, the delta-crys mRNA was expressed in the post
      ventral region of RP and the anterior region of RP. delta-crys mRNA expression
      was then restricted to the cephalic lobe of the pituitary gland. From stage 20,
      the delta-crys and alpha-glycoprotein subunit (alphaGSU) mRNA-expressing regions
      were almost completely overlapping. The alphaGSU mRNA-expressing region is
      thought to be the primordium of the pars tuberalis, and these regions were
      overlapped with the Lhx3 mRNA-expressing region. The intensity of delta-crys mRNA
      expression gradually decreased with development and completely disappeared by
      stage 34. These results suggest that the embryonic chick pituitary gland consists
      of two different regions labeled with delta-crys and Lhx3.

PMID- 22461198
TI  - Expression pattern of tumor necrosis factor alpha in placentae of idiopathic
      fetal growth restriction.
AB  - Tumor Necrosis Factor-Alpha (TNF-alpha) is one of the proinflammatory cytokines
      that provokes a variety of biological effects on the placenta. The increased
      placental exposure to TNF-alpha have induced impaired fetal development in
      experimental animals, but no data are available on the expression and
      localization of TNF-alpha in human placenta of idiopathic fetal growth
      restriction (FGR). The aim of this study was to characterize the
      immunohistochemical expression and localization of TNF-alpha in idiopathic FGR
      placentae in comparison with those of appropriate for gestational age (AGA)
      fetuses. 75 human placentae were collected between April, 2010 and March, 2011;
      50 placentae were collected from pregnancies associated with idiopathic FGR and
      25 placentae from AGA pregnancies. Histological and Immunohistochemical
      methodologies were employed in formalin fixed paraffin-embedded sections from the
      placentae of all subjects. Area percent of TNF-alpha immunostaining was evaluated
      using image analysis technique. In both AGA and idiopathic FGR placentae,
      cytoplasmic TNF-alpha was localized in the decidual and chorionic trophoblasts
      and in the endothelium of decidual and chorionic vessels. Trophoblast giant cells
      (TGC) in the decidua and chorionic villi of AGA specimens show deficient or
      negative TNF-alpha immunoexpression while those of idiopathic FGR show positive
      immunostaining. The mean area percent of TNF-alpha staining was greater in
      idiopathic FGR placentae (5.93 +/- 0.69) compared to AGA ones (3.28 +/- 0.41) (p
      = 0.001). Enhanced placental expression and specific cellular localization and of
      TNF-alpha are expected to contribute to impaired fetal development in idiopathic
      FGR and the TGCs are proposed to be an obvious source of this cytokine in such
      cases.

PMID- 22461197
TI  - The expression pattern of FHL2 during mouse molar development.
AB  - Four and a half LIM domains 2 (FHL2) functions as a transcriptional co-activator
      or co-repressor in a cell-type-specific manner. As a positive regulator, FHL2
      plays an important role in osteoblast differentiation and bone formation. Our
      previous study showed that FHL2 was expressed in odontoblasts in mature human
      teeth under normal and pathological conditions. The purpose of this study was to
      investigate the spatial-temporal expression patterns of FHL2 at different stages
      of mouse molar development by immunohistochemistry. Our results showed that at
      the bud and cap stage, FHL2 was expressed both in enamel organ and the underlying
      mesenchyme. At the early bell stage, FHL2 appeared in the inner and outer enamel
      epithelium, stratum intermedium and the secondary enamel knot. Positive staining
      gradually converged at the cusps of dental papilla. At the late bell stage, FHL2
      was expressed in the terminal differentiated ameloblasts and odontoblasts and
      stratum intermedium. At the postnatal day, FHL2 was detected in the secretory and
      mature ameloblasts and odontoblasts and mature enamel, and gradually appeared at
      Hertwig's epithelial root sheath and periodontal tissues. The spatial-temporal
      expression patterns of FHL2 from the bud stage to the postnatal day (13.5)
      suggested that during tooth development, FHL2 might play an important role in
      ameloblast and odontoblast differentiation, secretion of enamel and dentin
      matrix, mineralization of enamel, molar crown morphogenesis, as well as root
      formation.

PMID- 22461199
TI  - Effect of feeding different levels of foliage from Erythrina variegata on the
      performance of growing goats.
AB  - The effect of feeding different levels of foliage from Erythrina variegata on the
      performance of growing goats was studied using a local breed (Ma T'ou) with an
      average initial body weight of 11.2 kg (SD = 0.9). Twenty-four animals were
      allocated to a randomized design, with six animals (three males and three
      females) per treatment. The treatments were four different levels of replacement
      of the diet crude protein (CP) with CP from Erythrina foliage (EF) at 0 % (E-0),
      20 % (E-20), 40 % (E-40), and 60 % (E-60). There were no significant differences
      in the dry matter (DM) intake between treatments, but total CP intake was
      significantly higher in the goats fed the diet E-60 compared to E-20 (61.1 and
      51.4 g/day, respectively). The average daily liveweight gain of the goats did not
      differ between treatments and ranged from 51 to 63 g/day. Sixteen animals were
      kept in metabolism cages for a digestibility study and given with the same four
      diets as in the main experiment. The digestibility of DM, organic matter, neutral
      detergent fiber, and acid detergent fiber was significantly higher for diet E-60
      than for E-0. Neither the apparent digestibility of CP and N retention nor
      carcass characteristics (16 animals) differed with an increase in the level of CP
      from EF in the diets. In conclusion, CP from EF can replace up to 60 % of CP from
      a mixed diet with soybean meal without any negative effect on the growth in
      goats.

PMID- 22461200
TI  - Estrus response and follicular development in Boer does synchronized with
      flugestone acetate and PGF2alpha or their combination with eCG or FSH.
AB  - The effects of different estrus synchronization techniques on follicular
      development and estrus response were studied in 81 nulliparous Boer does. The
      does were divided into nine groups. Eight of the nine groups were synchronized
      with prostaglandin F2-alpha (PGF(2alpha)) or flugestone acetate (FGA) or their
      combinations, and the ninth group was a control group. In addition to the above
      combinations, four of the eight synchronized groups were given 5 mg follicle
      stimulating hormone (FSH) and the remaining four groups were administered 300 IU
      equine chorionic gonadotrophin (eCG). Posttreatment follicular development was
      monitored until ovulation occurred using a real-time B-mode ultrasound scanner
      (Aloka, 500 SSD, Japan), with a 7.5-MHz transrectal linear probe. All the does
      from the synchronized groups that were given eCG exhibited oestrus while only
      88.9% of the does synchronized with FSH showed estrus. The estrus response was
      observed to be the least among the does synchronized with PGF(2alpha) + FSH
      (33.3%) combination followed closely by the FGA + FSH (42.9%) combinations. It
      was observed that the combinations of FGA + PGF(2alpha) + FSH resulted in
      increased percentage of estrus response, duration of estrus, and ovulation. The
      number of follicles was higher (P < 0.05) in FSH-synchronized groups than the eCG
      synchronized groups. It was concluded that the best estrus synchronization
      protocol in goats is the FGA + eCG with or without PGF(2alpha). However, the
      PGF(2alpha) + FGA + FSH method of estrus synchronization is the most promising
      combination for further development as a better alternative to estrus
      synchronization with eCG in does.

PMID- 22461202
TI  - Advances in fingerprint analysis.
AB  - Fingerprints have been used in forensic investigations for the identification of
      individuals since the late 19th century. However, it is now clear that
      fingerprints can provide significantly more information about an individual.
      Here, we highlight the considerable advances in fingerprinting technology that
      can simultaneously provide chemical information regarding the drugs ingested and
      the explosives and drugs handled by a person as well as the identity of that
      individual.

PMID- 22461201
TI  - Energy expenditure and bone formation share a common sensitivity to AP-1
      transcription in the hypothalamus.
AB  - The regulation of bone and fat homeostasis and its relationship to energy
      expenditure has recently been the focus of increased attention because of its
      potential relevance to osteoporosis, obesity, and diabetes. Although central
      effectors within the hypothalamus have been shown to contribute to the regulation
      of both energy balance and bone homeostasis, little is known of the underlying
      mechanisms, including the possible involvement of transcriptional factors within
      the hypothalamus. Transgenic mice overexpressing DeltaFosB, a splice variant of
      the AP-1 transcription factor FosB with mixed agonist-antagonistic properties,
      have increased energy expenditure and bone mass. Because these mice express
      DeltaFosB in bone, fat, and hypothalamus, we sought to determine 1) whether
      overexpression of DeltaFosB within the hypothalamus was sufficient to regulate
      energy expenditure and whether it would also regulate bone mass, and 2) whether
      these effects were the result of antagonism to AP-1. Our results show that
      stereotactic injection of an adeno-associated virus vector to restrict
      overexpression of DeltaFosB to the ventral hypothalamus of wild-type mice induced
      a profound increase in both energy expenditure and bone formation and bone mass.
      This effect was phenocopied, at an even stronger level, by overexpression of a
      dominant-negative DNJunD, a pure AP-1 antagonist. Taken together, these results
      suggest that downregulation of AP-1 activity in the hypothalamus profoundly
      increases energy expenditure and bone formation, leading to both a decrease in
      adipose mass and an increase in bone mass. These findings may have physiological
      implications because DeltaFosB is expressed and regulated in the hypothalamus.

PMID- 22461203
TI  - Childhood enuresis is a risk factor for bladder dysfunction in adult life?
AB  - AIMS: To verify the relationship between enuresis in childhood and the type of
      urinary incontinence in adults, considering the gender and age. METHODS: In this
      retrospective cohort study the database used contained the records of patients
      who had with urinary complaints and underwent urodynamic studies in the period
      from 1999 to 2008. A multinomial logistic regression model was adjusted for the
      type of UI. RESULTS: A total of 661 patient records were analyzed, 585 (88.5%)
      women and 76 (11.5%) men, with mean age 54 (SD = 13.3). Patients with urge
      urinary incontinence (UUI) were compared to those with stress urinary
      incontinence (SUI) and the variables associated were the presence of enuresis in
      childhood (OR = 2.37, IC: 1.43-3.92) and age >50 years (OR = 2.64, CI: 1.68
      4.15). Comparing patients with mixed urinary incontinence (MUI) and SUI, the
      presence of enuresis was also associated ((OR = 1.77, CI: 1.15-2.73) and the age
      of more than 50 years (OR = 1.71, CI: 1.19-2.44). For both categories of urinary
      incontinence, the variable sex was not associated. CONCLUSIONS: Individuals with
      MUI and UUI in adult life were more likely to have a history of enuresis in
      childhood than those with SUI.

PMID- 22461204
TI  - Public perceptions of key performance indicators of healthcare in Alberta,
      Canada.
AB  - OBJECTIVE: To examine the relationship between public perceptions of key
      performance indicators assessing various aspects of the health-care system.
      DESIGN: Cross-sequential survey research. Annual telephone surveys of random
      samples of adult Albertans selected by random digit dialing and stratified
      according to age, sex and region (n = 4000 for each survey year). The survey
      questionnaires included single-item measures of key performance indicators to
      assess public perceptions of availability, accessibility, quality, outcome and
      satisfaction with healthcare. Cronbach's alpha and factor analysis were used to
      assess the relationship between key performance indicators focusing on the health
      care system overall and on a recent interaction with the health-care system.
      SETTING: The province of Alberta, Canada during the years 1996-2004.
      PARTICIPANTS: Four thousand adults randomly selected each survey year. MAIN
      OUTCOME MEASURE(S): Survey questions measuring public perceptions of healthcare
      availability, accessibility, quality, outcome and satisfaction with healthcare.
      RESULTS: Factor analysis identified two principal components with key performance
      indicators focusing on the health system overall loading most strongly on the
      first component and key performance indicators focusing on the most recent health
      care encounter loading most strongly on the second component. Assessments of the
      quality of care most recently received, accessibility of that care and perceived
      outcome of care tended to be higher than the more general assessments of overall
      health system quality and accessibility. CONCLUSION: Assessments of specific
      health-care encounters and more general assessments of the overall health-care
      system, while related, nevertheless comprise separate dimensions for health-care
      evaluation.

PMID- 22461205
TI  - What constitutes patient safety culture in Chinese hospitals?
AB  - OBJECTIVE: To develop a patient safety culture instrument for use in Chinese
      hospitals, we assessed the appropriateness of existing safety culture
      questionnaires used in the USA and Japan for Chinese respondents and identified
      new items and domains suitable to Chinese hospitals. DESIGN: Focus group study.
      SETTING AND PARTICIPANTS: Twenty-four physicians, nurses and other health-care
      workers from 11 hospitals in three Chinese cities. METHODS: Three focus groups
      were conducted in 2010 to elicit information from hospital workers about their
      perceptions of the appropriateness and importance of each of 97 questionnaire
      items, derived from a literature review and an expert panel, characterizing
      hospital safety culture. RESULTS:  PARTICIPANTS: understood the concepts of
      patient safety and safety culture and identified features associated with safe
      care. They judged that numerous questions from existing surveys were
      inappropriate, including 39 items that were dropped because they were judged
      unimportant, semantically redundant, confusing, ambiguous or inapplicable in
      Chinese settings. Participants endorsed eight new items and three additional
      dimensions addressing staff training, mentoring of new hires, compliance with
      rules and procedures, equipment availability and leadership walk-rounds they
      judged appropriate to assessing safety culture in Chinese hospitals. This process
      resulted in a 66-item instrument for testing in cognitive interviews, the next
      stage of survey development. CONCLUSIONS: Focus group participants provided
      important insights into the refinement of existing items and the construction of
      new items for measuring patient safety culture in Chinese hospitals. This is a
      necessary first step in producing a culturally appropriate instrument applicable
      to specific local contexts.

PMID- 22461206
TI  - Endohedral metallofullerenes-filled fullerene derivatives towards multifunctional
      reaction center mimics.
AB  - In recent years, endohedral metallofullerenes have attracted tremendous interest
      not only in physics and chemistry, but also in interdisciplinary areas, such as
      materials and biological sciences. In this concept article we highlight recent
      results on different endohedral metallofullerenes based on lanthanides and their
      derivatives. The chemical and excited state reactivities of endohedral
      metallofullerenes are discussed for various endohedral clusters. Most important
      is the part that covers spectroscopic and kinetic assays of reductive and
      oxidative charge transfer evolving from photoexcited electron donors and electron
      acceptors, respectively, in a variety of electron donor-acceptor conjugates.
      Towards this end, we refer to the applications of endohedral metallofullerenes in
      photovoltaic devices that feature greater efficiency than devices fabricated with
      empty fullerenes. Herein, we focus mainly on results obtained in the groups of
      Akasaka, Echegoyen, and Guldi.

PMID- 22461207
TI  - Amphiphilic folded dendrimer discs and their thermosensitive self-assembly in
      water.
AB  - Folded dendrimers with peripheral ether side chains show a thermally induced
      hierarchical aggregation process, in which the transition temperature and the
      dimensions of the aggregates can readily be tuned via the generation number (see
      figure).

PMID- 22461208
TI  - Psychological distress in cancer patients with underage children: gender-specific
      differences.
AB  - BACKGROUND: Findings on gender differences in the psychological distress of
      cancer patients have been inconsistent. The objectives of the current study were
      to examine whether being a parent differentially modulates anxiety and depression
      in men and women and to compare whether psychological distress differs in male
      and female patients with and without children. METHODS: There were 235 patients
      (77% female, 23% male) with different cancer types included in the group with
      underage children (age <18 years). The comparison group with no children
      comprised 85 patients. Psychological distress was assessed via the Hospital
      Anxiety and Depression Scale within 12 months after first diagnosis or during
      treatment of metastases. RESULTS: In the patient group with underage children,
      women tended to report more anxiety than men. The comparison with the patient
      group without children, however, revealed that men were significantly more
      affected by anxiety when they had children, whereas in women, anxiety ratings did
      not differ between the groups. Men tended to report more depressive symptoms, but
      depression was not differentially associated with parenthood. A binary logistic
      regression showed that in men with cancer, anxiety, as well as depression, was
      highly related to unemployment. In women, occurrence of metastases as well as
      suffering from other cancer types than breast cancer was associated with higher
      ratings of anxiety. CONCLUSION: Even though our findings need to be supported in
      future investigations using larger sample sizes, they imply that male cancer
      patients with underage children are in particular need of psychosocial support.

PMID- 22461209
TI  - Thiazolidinediones and bone.
AB  - Diabetes mellitus and osteoporosis are two frequent multifactorial medical
      conditions with an increasing prevalence in the aging population. Patients with
      type 2 diabetes mellitus have an increased fracture risk despite a higher bone
      mineral density (BMD), which is mainly due to the increased risk of falls.
      Adequate glycemic control and prevention of diabetic complications are also the
      mainstay of therapy in type 2 diabetes mellitus. The thiazolidinediones (TZDs)
      have been demonstrated to improve insulin sensitivity and currently represent a
      widely prescribed treatment for type 2 diabetes. Their action is mediated by the
      binding to the nuclear receptor and transcription factor, peroxisome proliferator
      activated receptor- gamma (PPAR- gamma), regulating the activity of other
      transcription factors in the adipogenic differentiation and inflammatory response
      pathways. The activation of PPAR- gamma by TZDs may also cause an increase in
      bone marrow adiposity and a decrease in osteoblastogenesis, resulting in reduced
      bone formation. Clinical data are pointing out that the intake of
      thiazolidinediones by older patients with type 2 diabetes correlates with both
      the decrease of bone mineral density in the femoral neck and hip and a higher
      risk for fractures. Thus, health care providers, not only physicians, should
      carefully check the existence of risk factors for osteoporosis and factures in
      their patients before selecting them for thiazolidinediones treatment. Moreover,
      an adequate clinical follow-up of treated subjects is strongly recommended.

PMID- 22461210
TI  - The orthopaedic treatment of fragility fractures.
AB  - The purpose of this review is the presentation of the proper orthopaedic
      treatment of the most frequent fragility fractures associated with low bone
      mineral density or established osteoporosis. In this particular group of
      patients, the surgical treatment is difficult for the poor quality of the broken
      bone that limits the reduction, the hardware fixation and the physiologic process
      of bone healing. Other important problems are the postoperative management of old
      patients with chronic diseases and more prone to develop local and general
      complications with big difficulties to conduct a good rehabilitation program.Some
      considerations will be made, lastly, about the role of the orthopaedic surgeon on
      the treatment of osteoporosis and on the possibility to prevent further
      fractures.

PMID- 22461211
TI  - Calcitonin and calcitonin receptors.
AB  - Calcitonin (CT) is a polypeptide hormone with 32 aminoacids syntetized primarily
      by the thyroid.Several evidences support the existence of nonthyroidal CT like
      peptide. The CT gene transcript also encodes a distinct peptide known as
      calcitonin gene related peptide (CGRP) which is a potent vasodilator and
      responsible for the stimulation of the glomerular filtration rate. In addition, a
      37 aminoacid peptide amylin has been originally isolated by pancreatic beta
      cells. Amylin is able to inhibit insulin secretion, glucose transport into the
      skeletal musculature and gluconeogenesis. It is also able to inhibit gastric
      emptying. In the kidney it is able to modulate Calcium (Ca(2+)) excretion and
      increases renin activity. Finally, high affinity amylin receptors have been
      identified in the brain of the rat. The calcitonin receptor (CTR) is a member of
      a subfamily of the seven-transmembrane domain G-protein coupled receptor super
      family that includes several peptides. Members of this family have a similar
      structure with other seven-membrane-spanning domain G-protein coupled
      receptors.The genetic contribution to osteoporosis susceptibility is well
      documented and many studies demonstrated that genetic factors play important
      roles in the regulation of bone metabolism. Restriction Fragment Length
      Polymorphisms (RFLPs) for the CTR gene have been described in the literature with
      a positive association with the lumbar bone mineral density (BMD), femoral neck
      BMD and with a lower incidence of vertebral fractures.

PMID- 22461212
TI  - Phytoestrogens: food or drug?
AB  - Within the past several years, the relation between diet and health has been
      accepted by the mainstream nutrition community and in this connection interest in
      the physiological role of bioactive compounds present in plants has dramatically
      increased over the last decade.The phytoestrogens are bioactive molecules present
      as nutritional constituents of widely consumed vegetables. Their name derives
      from the fact that they are able to bind to estrogen receptors and to induce an
      estrogenic/antiestrogenic response in target tissues. Natural estrogens are
      involved in a multiplicity of programmed events in target tissues as uterus,
      breast, pituitary gland and hormone responsive tumors. Phytoestrogens are present
      in many human foodstuffs including fruits (plum, pear, apple grape berries, ...),
      vegetables (beans, sprouts, cabbage, spinach, soybeans, grains, hops, garlic,
      onion,...), wine, tea, and they have been identified in a number of botanical
      dietary supplements. They include a wide variety of structurally different
      compounds such as isoflavones, mainly found in soy, lignans found in grains,
      stilbenes found in the skin of grapes. Other less investigated compounds include
      flavones, flavans, isoflavanes and coumestans. The estrogenic or antiestrogenic
      activity of any chemicals depends on the ability of the compound to interact with
      the ERs (ERalpha , ERbeta ).This article reported the knowledge about the
      activity of phytoestrogens from a pharmacological point of view for their
      estrogenicity or antiestrogenicity.

PMID- 22461214
TI  - A novel polymorphism at the GNAS1 gene associated with low circulating calcium
      levels.
AB  - The concentration of calcium in the extracellular fluid is crucial for several
      physiological functions in humans and in normal conditions its circulating levels
      are maintained between 8.5-10.5 mg/dl. Among the regulators of calcium
      homeostasis parathyroid hormone (PTH) acts though the G-protein coupled PTH
      receptor and a hormone-sensitive adenylate cyclase, with Gsalpha subunit
      (stimulatory guanine nucleotide-binding protein alpha-subunit) being responsible
      for the stimulation of the catalytic complex. Mutations of the Gsalpha encoding
      gene, GNAS1, are causal for some forms of congenital hypocalcemia. In the present
      study genetic variability in the GNAS1 gene was analyzed in a group of
      hypocalcemic patients collected through the Italian Register of Primary
      Hypoparathyroidism (RIIP). We identified a new intronic variant of the GNAS1
      gene, consisting of a T>C polymorphism. This polymorphism was studied in a group
      of unrelated healthy subjects for a possible association with bone turnover
      biomarkers and bone mineral density. The T>C polymorphism was found in 18% of the
      studied populations, with 15% heterozygous TC and 3% homozygous CC (Pearson
      chi(2)analysis: p=0.04). A significant association with low serum calcium levels
      was found in healthy subjects carrying the T > C polymorphism (ANCOVA analysis:
      p=0.04). These results support segregation of a novel GNAS1 gene intronic variant
      with low calcium levels in primary hypoparathyroidism, pseudo-hypoparathyroidism
      and in the general population.

PMID- 22461213
TI  - Bone mass pharmacogenetics and ethnic health implications.
AB  - Osteoporosis is a common skeletal disease with a strong genetic component
      characterized by reduced bone mass and increased risk of fragility fractures.
      Bone mineral density (BMD) is considered the best established risk factor for
      osteoporotic fractures.Over the last years a large number of studies have pointed
      to the variability in many target genes and their relation with BMD and other
      determinants of fracture risk such as ultrasound bone properties, skeletal
      geometry and bone turnover markers. The importance of genetic factors in the bone
      quality is substantial, but no consensus exists yet on the genes that are
      involved.Although osteoporosis is world healthy problem, there are many
      differences in human ethnics regarding both disease morbidity and drug treatment
      efficacy. Heterogeneity in drug response may reflect varying responsiveness to
      osteoporosis treatments due to allele variation in signaling pathway genes such
      as vitamin D receptor (VDR) or estrogen receptor alpha (ERalpha). Polymorphisms
      of VDR and ERalphaloci appear genetic determinants of their corresponding
      hormonal treatment response such as vitamin D and estrogens. Because of their
      specific ethnic distribution, polymorphisms of VDR and ERalphagenes may be
      involved in reported human differences of osteoporosis treatment
      responses.Knowledge of the molecular and functional consequences of the gene
      polymorphisms is crucial to fully appreciate their significance and understand
      their potential clinical implications. Future studies and preventive strategies
      to management osteoporosis need to take in account these genetic factors.

PMID- 22461215
TI  - Clodronate acts on human osteoclastic cell proliferation, differentiation and
      function in a bioreversible manner.
AB  - Background. Clodronate is used in high bone resorption diseases. Its action was
      defined as "cytotoxic" based on the induced cellular ATP loss, without any
      experimental verification of reversibility. In the present report the
      reversibility of clodronate action was tested on cultured human osteoclastic cell
      cultures. As "in vitro" bioeffects of clodronate are reversible, this compound
      should not be defined as "cytotoxic".Introduction. Bisphosphonates are
      pyrophosphate analogs able to inhibit osteoclast-mediated bone resorption widely
      used in the treatment of diseases with high bone turnover. Several evidences have
      shown that bisphosphonates can be divided into two groups with distinct molecular
      mechanisms of action depending on the nature of the R(2)side chain. The nitrogen
      containing bisphosphonates act on osteoclasts by preventing protein prenylation,
      while non-nitrogen-containing bisphosphonates, like clodronate, are metabolized
      intracellularly to a beta-gamma-methylene analog of ATP that induces inhibition
      of the ADP/ATP translocase.Materials and Methods. In order to evaluate clodronate
      effects on osteoclastic cells and the bioreversibility of its action, we have
      used a human preosteoclastic (FLG 29.1) cell line and primary cultures of human
      osteoclast-like (HOC) cells. Functional and differentiative modifications were
      evaluated with immunocytochemical tartrate-resistant acid phosphatase activity
      (TRAcP) assay and with rapid quantitative detection of the complex "matrix
      metalloproteinase 9/tissue inhibitor of metalloproteinase" (MMP9/TIMP1) by RT-PCR
      analysis based on "TaqMan" technology. The apoptosis phenomenon were detected by
      DNA ladder analysis and quantified by counting apoptotic cells with Transmission
      Electron Microscopy (TEM) analysis. Adenosine-5'-[ beta - gamma 
      dichloromethylene] triphosphate (AppCCl(2)p) was detected and identified in cell
      extract by HPLC-ESI-MS-MS Mass Spectrometry. Intracellular ATP modulation in the
      presence of clodronate was evaluated by luciferin-luciferase assay. The Mann
      Whitney "U" test was conducted for statistical analysis.Results. We found that
      clodronate inhibited both proliferation and differentiative features of cells of
      the osteoclastic lineage. Furthermore, treatment of both cell types with
      clodronate caused apoptosis, generation of measurable levels of AppCCl(2)p, and
      reduction of intracellular ATP levels. Addition of ATP to the culture medium
      caused an inhibition of the biological actions of clodronate on the human
      osteoclastic cell lineage.Conclusions. These data indicate that intracellular
      accumulation of the metabolite AppCCl(2)p is the likely route by which clodronate
      inhibits osteoclastic function and this effect is reversed by ATP.

PMID- 22461216
TI  - The role of osteoprotegerin (OPG) and estrogen receptor (ER-alpha) gene
      polymorphisms in rheumatoid arthritis.
AB  - Objective. Osteoclast activation at the cartilage pannus junction is an essential
      step in the destruction of bone matrix in patients affected by rheumatoid
      arthritis (RA). Receptor activator of NFkappaB ligand (RANK-L) is responsible for
      osteoclast differentiation and activation. Osteoprotegerin (OPG) is an
      alternative, high-affinity soluble receptor for RANK-L which significantly
      inhibits osteoclastogenesis. Estrogens and the specific receptors alpha and beta
      (ER-alpha and ER-alpha) are known to play an important role in the
      pathophysiology of osteoarthritis (OA). Scope of the present study is to
      investigate the role of ER-alpha and OPG gene polymorphisms in a group of women
      affected by RA.Materials and Methods. 139 consecutive RA patients (115 females
      and 34 males; median age 65.8 years) were selected. Bone mineral density (BMD)
      was measured by dual energy x-ray absorptinometry at the lumbar spine (LS-BMD)
      and femoral neck (FN-BMD) and the presence of bone erosions was evaluated by
      conventional X-ray. ER-alpha gene polymorphisms were determined by PvuII and XbaI
      restriction endonuclease digestion of polymerase chain reaction (PCR) products.
      By convention, the presence of the endonuclease restriction site was indicated
      with lowercase (p and x) letters while the absence of the restriction site was
      indicated with uppercase letters (P and X). OPG gene polymorphism was determined
      by RsaI restriction endonuclease digestion of PCR products and the presence and
      absence of restriction fragment was identified as TT and CC respectively.Results.
      Pearson's chi(2)analysis for the ER-alpha gene polymorphism showed a prevalence
      of Pp genotype (58%) (p=0.04) and Xx (54%) (p=0.04) in the total population,
      without differences between males and females. We did not observed any
      significant differences between ER-alpha genotypes and LS-BMD. However subjects
      with xx or pp genotype had a lower LS-BMD in comparison with the opposite
      genotype.For OPG gene polymorphism, non significant differences in the
      distribution of the genotypes were observed between males and females. In
      addition, we did not observed significant differences on LS-BMD between the
      genotypes.Finally, we observed that patients with ER-alpha pp genotype was
      significant more represented in patients with hand erosions (p = 0.05). No
      significant correlation was observed for ER-alpha XbaI genotype, however a trend
      characterized by a correlation between xx and hand erosions was observed (p =
      0.13). For OPG gene polymorphism, we found a statistical correlation between C
      allele of OPG and hands bone erosions (p = 0.02).Conclusion. We found a
      significant association between ER-alpha and OPG gene polymorphisms and the
      presence of bone erosions in RA patients. These preliminary data suggest a role
      of ER-alpha and OPG gene polymorphisms in bone turnover and disease progression.

PMID- 22461217
TI  - Role of observational studies in assessing osteoporosis therapies: the REAL
      study.

PMID- 22461218
TI  - Declaration on Vitamin D in Osteoporosis Management: From the European Summit on
      the Role of Vitamin D in the Management of Osteoporosis: a MetaForum.

PMID- 22461219
TI  - Anatomical examination of the great inguinal blood vessels in preterm and term
      neonates.
AB  - It is generally accepted that vessel cannulation is technically more difficult
      and results in more complications in neonates. A sound anatomical knowledge of
      the inguinal area is therefore important in the selection of appropriately sized
      central line catheters as well as the approach to central vessel access. Eleven
      stillborns were investigated. Birth weight (mean: 2,414 g, 900-4,100 g) and
      gestational age (mean 34 1/7 weeks', 27 6/7-42 1/7) varied within normal range.
      The outer diameters of the femoral artery (FA), femoral vein (FV), and great
      saphenous vein (GSV) were determined. The distance between the anterior superior
      iliac spine and the pubic tubercle was set as 100% and the vessel intersection
      points were calculated as percentage values of the inguinal ligament length,
      starting at the iliac spine. The FA has a diameter of 1.9 +/- 0.5 mm without
      correlation to gestational age. The FA crosses the inguinal ligament centrally.
      The FV has a diameter of 3.1 +/- 1.0 mm and does have correlation to gestational
      age. The FV crosses the inguinal ligament at 63-64%. The GSV has a diameter of
      1.4 +/- 0.7 mm. Its point of intersection at the level of the inguinal ligament
      is 68-70%. We conclude that cannulation of the femoral artery or vein should not
      be performed too far (<1 cm) from the inguinal ligament. The course of the GSV is
      not suitable for catheter insertion.

PMID- 22461220
TI  - Optical properties of assembled single-walled carbon nanotube gels.
AB  - A macroscopic system of single-walled carbon nanotubes (SWNTs) created by a novel
      DNA/protein complex-assisted assembly is investigated. Due to a point-like nature
      of connectors, the resulting SWNT aerogel represents a network of self-suspended
      nanotubes with a record-low density of less than 0.75 mg cm(-3). The assembly
      method and low density enable a direct comparison of optical properties of
      nanotubes in solvent and air to surfactant solubilized nanotubes. Optical
      properties of SWNT gels are investigated using optical absorption,
      photoluminescence, and Raman spectroscopy. Gelled nanotubes in water and in the
      low-energy regime behave similar to solubilized nanotubes. In contrast, the
      photoluminescence of SWNT aerogels exhibits a previously unobserved peak at 1.3
      eV that corresponds to a phonon-assisted recombination of photoexcited charges.
      This new emission pathway is the result of the unique nature of self-suspended
      nanotubes in aerogel and a reduced phonon decay.

PMID- 22461221
TI  - Application of neuroanatomical features to tractography clustering.
AB  - Diffusion tensor imaging allows unprecedented insight into brain neural
      connectivity in vivo by allowing reconstruction of neuronal tracts via captured
      patterns of water diffusion in white matter microstructures. However,
      tractography algorithms often output hundreds of thousands of fibers, rendering
      subsequent data analysis intractable. As a remedy, fiber clustering techniques
      are able to group fibers into dozens of bundles and thus facilitate analyses.
      Most existing fiber clustering methods rely on geometrical information of fibers,
      by viewing them as curves in 3D Euclidean space. The important neuroanatomical
      aspect of fibers, however, is ignored. In this article, the neuroanatomical
      information of each fiber is encapsulated in the associativity vector, which
      functions as the unique "fingerprint" of the fiber. Specifically, each entry in
      the associativity vector describes the relationship between the fiber and a
      certain anatomical ROI in a fuzzy manner. The value of the entry approaches 1 if
      the fiber is spatially related to the ROI at high confidence; on the contrary,
      the value drops closer to 0. The confidence of the ROI is calculated by diffusing
      the ROI according to the underlying fibers from tractography. In particular, we
      have adopted the fast marching method for simulation of ROI diffusion. Using the
      associativity vectors of fibers, we further model fibers as observations sampled
      from multivariate Gaussian mixtures in the feature space. To group all fibers
      into relevant major bundles, an expectation-maximization clustering approach is
      employed. Experimental results indicate that our method results in anatomically
      meaningful bundles that are highly consistent across subjects.

PMID- 22461222
TI  - Non-linear microscopy of smooth muscle cells in artificial extracellular matrices
      made of cellulose.
AB  - Non-linear microscopy has been used to characterize bovine smooth muscle cells
      and their proliferation, migration, and differentiation in hydrogel cellulose
      scaffolds, toward the development of fully functional blood vessel implants. The
      extracellular matrix (ECM) composed of cellulose and endogenous collagen fibers
      was imaged using Second Harmonic Generation (SHG) microscopy and the cell
      morphology by Coherent Anti-Stokes Raman Scattering (CARS) microscopy. Images
      prove that cells adhere on the cellulose scaffold without additional surface
      modification and that both contractile and proliferating phenotypes are
      developed. This work shows that non-linear microscopy contributes with unique
      insights in cell interactions with (artificial) ECM components and has the
      potential to become an established characterization method in tissue engineering.

PMID- 22461223
TI  - Validation of the Finnish Autism Spectrum Screening Questionnaire (ASSQ) for
      clinical settings and total population screening.
AB  - We assessed the validity and determined cut-off scores for the Finnish Autism
      Spectrum Screening Questionnaire (ASSQ). A population sample of 8-year-old
      children (n = 4,408) was rated via the ASSQ by parents and/or teachers, and a
      subgroup of 104 children was examined via structured interview, semi-structured
      observation, IQ measurement, school observation, and medical records. Autism
      spectrum disorders (ASDs) were diagnosed following DSM-IV-TR criteria. A search
      for hospital-registered ASDs was performed. For Finnish higher-functioning
      primary school-aged, 7- to 12-year-olds, the optimal cut-off score was 30 in
      clinical settings and 28 in total population screening using summed ASSQ scores
      of parents' and teachers' ratings. Determining appropriate cut-off scores in ASD
      screening in different languages and in different cultures is of utmost
      importance.

PMID- 22461225
TI  - The impact of Staphylococcus aureus concentration on the development of pulmonary
      lesions and cytokine expression after intravenous inoculation of pigs.
AB  - Acute respiratory distress syndrome is a common complication in severe sepsis. In
      pigs, the lungs play an important role in clearing systemic bacterial infections
      due to pulmonary intravascular macrophages found specifically in pigs. However,
      this increases the exposure of the porcine lungs to pathogens and potential
      injury. The authors propose that increasing the concentration of the inoculum
      without changing the bacterial dose will lead to severe sepsis with pronounced
      pulmonary lesions. This could potentially create a risk of cytokine spillover to
      the circulation, leading to an increased systemic response. Eight Danish Landrace
      pigs, approximately 10 weeks old, were inoculated twice with a low or once with a
      high concentration of Staphylococcus aureus. Three pigs were sham-inoculated. The
      animals were grouped based on macro- and microscopic lung lesions. The mRNA
      expression of local pulmonary inflammatory markers was compared to protein levels
      of systemic inflammatory markers. The most severe pulmonary lesions were observed
      in animals receiving the high S. aureus concentration, indicating that severity
      of lesions is dependent on inoculum concentration rather than total numbers of
      bacteria. Furthermore, local mRNA expression of inflammatory cytokines appeared
      to be dependent on the magnitude and severity of tissue destruction, including
      the ability to confine the lesions. Increasing mRNA levels of serum amyloid A
      could be a confident marker of severity of pulmonary lesions. Since no
      correlation was observed between local and systemic levels of inflammatory
      cytokines, this finding could indicate an ability of the porcine lung to
      compartmentalize the local inflammatory response and thus restrict systemic
      contribution.

PMID- 22461226
TI  - Kinetics of lung lesion development and pro-inflammatory cytokine response in
      pigs with vaccine-associated enhanced respiratory disease induced by challenge
      with pandemic (2009) A/H1N1 influenza virus.
AB  - The objective of this report was to characterize the enhanced clinical disease
      and lung lesions observed in pigs vaccinated with inactivated H1N2 swine delta
      cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human
      influenza virus. Eighty-four, 6-week-old, cross-bred pigs were randomly allocated
      into 3 groups of 28 pigs to represent vaccinated/challenged (V/C), non
      vaccinated/challenged (NV/C), and non-vaccinated/non-challenged (NV/NC) control
      groups. Pigs were intratracheally inoculated with pH1N1 and euthanized at 1, 2,
      5, and 21 days post inoculation (dpi). Macroscopically, V/C pigs demonstrated
      greater percentages of pneumonia compared to NV/C pigs. Histologically, V/C pigs
      demonstrated severe bronchointerstitial pneumonia with necrotizing bronchiolitis
      accompanied by interlobular and alveolar edema and hemorrhage at 1 and 2 dpi. The
      magnitude of peribronchiolar lymphocytic cuffing was greater in V/C pigs by 5
      dpi. Microscopic lung lesion scores were significantly higher in the V/C pigs at
      2 and 5 dpi compared to NV/C and NV/NC pigs. Elevated TNF-alpha, IL-1beta, IL-6,
      and IL-8 were detected in bronchoalveolar lavage fluid at all time points in V/C
      pigs compared to NV/C pigs. These data suggest H1 inactivated vaccines followed
      by heterologous challenge resulted in potentiated clinical signs and enhanced
      pulmonary lesions and correlated with an elevated proinflammatory cytokine
      response in the lung. The lung alterations and host immune response are
      consistent with the vaccine-associated enhanced respiratory disease (VAERD)
      clinical outcome observed reproducibly in this swine model.

PMID- 22461224
TI  - Enzyme replacement prevents enamel defects in hypophosphatasia mice.
AB  - Hypophosphatasia (HPP) is the inborn error of metabolism characterized by
      deficiency of alkaline phosphatase activity, leading to rickets or osteomalacia
      and to dental defects. HPP occurs from loss-of-function mutations within the gene
      that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). TNAP
      knockout (Alpl(-/-), aka Akp2(-/-)) mice closely phenocopy infantile HPP,
      including the rickets, vitamin B6-responsive seizures, improper dentin
      mineralization, and lack of acellular cementum. Here, we report that lack of TNAP
      in Alpl(-/-) mice also causes severe enamel defects, which are preventable by
      enzyme replacement with mineral-targeted TNAP (ENB-0040). Immunohistochemistry
      was used to map the spatiotemporal expression of TNAP in the tissues of the
      developing enamel organ of healthy mouse molars and incisors. We found strong,
      stage-specific expression of TNAP in ameloblasts. In the Alpl(-/-) mice,
      histological, uCT, and scanning electron microscopy analysis showed reduced
      mineralization and disrupted organization of the rods and inter-rod structures in
      enamel of both the molars and incisors. All of these abnormalities were prevented
      in mice receiving from birth daily subcutaneous injections of mineral-targeting,
      human TNAP at 8.2 mg/kg/day for up to 44 days. These data reveal an important
      role for TNAP in enamel mineralization and demonstrate the efficacy of mineral
      targeted TNAP to prevent enamel defects in HPP.

PMID- 22461227
TI  - Hybrid assemblies of Eu-containing polyoxometalates and hydrophilic block
      copolymers with enhanced emission in aqueous solution.

PMID- 22461228
TI  - Homo- and heteronuclear meso,meso-(E)-ethene-1,2-diyl-linked diporphyrins:
      preparation, x-ray crystal structure, electronic absorption and emission spectra
      and density functional theory calculations.
AB  - Homo- and heteronuclear meso,meso-(E)-ethene-1,2-diyl-linked diporphyrins have
      been prepared by the Suzuki coupling of porphyrinylboronates and
      iodovinylporphyrins. Combinations comprising 5,10,15-triphenylporphyrin (TriPP)
      on both ends of the ethene-1,2-diyl bridge M(2)10 (M(2) =H(2)/Ni, Ni(2), Ni/Zn,
      H(4), H(2)Zn, Zn(2)) and 5,15-bis(3,5-di-tert-butylphenyl)porphyrinato-nickel(II)
      on one end and H(2), Ni, and ZnTriPP on the other (M(2)11), enable the first
      studies of this class of compounds possessing intrinsic polarity. The compounds
      were characterized by electronic absorption and steady state emission spectra,
      (1)H NMR spectra, and for the Ni(2) bis(TriPP) complex Ni(2)10, single crystal X
      ray structure determination. The crystal structure shows ruffled distortions of
      the porphyrin rings, typical of Ni(II) porphyrins, and the (E)-C(2)H(2) bridge
      makes a dihedral angle of 50 degrees  with the mean planes of the macrocycles.
      The result is a stepped parallel arrangement of the porphyrin rings. The dihedral
      angles in the solid state reflect the interplay of steric and electronic effects
      of the bridge on interporphyrin communication. The emission spectra in
      particular, suggest energy transfer across the bridge is fast in conformations in
      which the bridge is nearly coplanar with the rings. Comparisons of the
      fluorescence behaviour of H(4)10 and H(2)Ni10 show strong quenching of the free
      base fluorescence when the complex is excited at the lower energy component of
      the Soret band, a feature associated in the literature with more planar
      conformations. TDDFT calculations on the gas-phase optimized geometry of Ni(2)10
      reproduce the features of the experimental electronic absorption spectrum within
      0.1 eV.

PMID- 22461229
TI  - Silver and gold complexes with a new 1,10-phenanthroline analogue N-heterocyclic
      carbene: a combined structural, theoretical, and photophysical study.
AB  - Unusual coordination for gold: an imidazolium salt was synthesized and used as a
      precursor for an N-heterocyclic carbene, which can be considered as the carbene
      analogue of 1,10-phenanthroline. Like the diimine congener, this ligand gives
      luminescent metal complexes. Remarkably, the Au(III) complex features a gold atom
      in an unusual environment: it is surrounded by six donor atoms, two of which
      interact electrostatically with the Au atom.

PMID- 22461231
TI  - Hybrid polymer-nanocrystal materials for photovoltaic applications.
AB  - Hybrid polymer-nanocrystal photovoltaic (PV) cells have received much attention
      during the past decade as promising low-cost solar energy harvesting devices, and
      showed significant progress with power conversion efficiency reaching 5%
      recently. This review starts from the introduction of hybrid materials to their
      application in electronic devices, with particular focus on bulk-heterojunction
      hybrid polymer-nanocrystal PV devices. The synthesis, surface chemistry, and
      electronic properties of colloidal inorganic nanocrystals are described. The
      recent development of hybrid PV devices will be discussed from the perspective of
      tailoring both inorganic nanocrystals and conjugated polymers, controlling
      polymer-nanocrystal hybrid morphology, engineering polymer-nanocrystal interface,
      and optimizing device architecture. Finally, future directions for further
      advancing hybrid PV technology to potential commercialization are also discussed.

PMID- 22461232
TI  - Characterization of oral squamous cell carcinoma based on higher-harmonic
      generation microscopy.
AB  - In vivo higher-harmonic generation microscopy (HGM) performed on healthy human
      oral mucosa not only provides images with a <500 nm lateral resolution at a 280
      MUm penetration depth, but also leaves no photodamages in the tissues. These
      advantages suggest that HGM could serve as an ideal virtual biopsy tool for in
      vivo, in situ, and immediate histopathological diagnosis of oral cancer. However,
      translation of such mechanism for clinical cancer diagnosis requires evidence
      based algorithm capable to differentiate cancerous tissues from normal. It is
      thus critical to investigate if the endogenous contrast provided by the HGM would
      be high enough to differentiate cancerous versus normal tissues in human oral
      mucosa. In this report, ex vivo HGM study was performed on the cancerous mucosa
      from 10 patients with oral squamous cell carcinoma. Compared with histology, HGM
      revealed histopathological features including the cytological abnormalities, loss
      of differentiation, interruption of basement membrane, and irregular epithelial
      stratification in all 10 specimens. In addition, distinct patterns of collagen
      fibers and increased distribution area of actin filaments in tumor cells were
      noted. These results indicate HGM holds great potential for the optical biopsy
      screening of oral cancer lesions.

PMID- 22461233
TI  - Resurrecting unclaimed bodies.

PMID- 22461235
TI  - Design, synthesis, and miniemulsion polymerization of new phosphonate surfmers
      and application studies of the resulting nanoparticles as model systems for
      biomimetic mineralization and cellular uptake.
AB  - Heterophase polymerizations have gained increasing attention in the past decades,
      especially as the decoration and functionalization of the particle surface for
      further applications gets more and more into focus. One promising approach for
      the functionalization exclusively on the particle surface is the use of surfmers
      (surfactant and monomer). Herein, we present the synthesis of a new family of
      surfmers and their use for decorating nanoparticles with phosphonate groups
      through miniemulsion polymerization. Furthermore the synthesis of a dye-labeled
      functional surfmer provided an elegant manner to evaluate and get deeper insights
      about its copolymerization. Additionally, potential applications of the
      synthesized particles in biological studies as well as their use as template for
      biomimetic mineralization are presented.

PMID- 22461234
TI  - A comparison of physiologic modulators of fMRI signals.
AB  - One of the main obstacles in quantitative interpretation of functional magnetic
      resonance imaging (fMRI) signal is that this signal is influenced by non-neural
      factors such as vascular properties of the brain, which effectively increases
      signal variability. One approach to account for non-neural components is to
      identify and measure these confounding factors and to include them as covariates
      in data analysis or interpretation. Previously, several research groups have
      independently identified four potential physiologic modulators of fMRI signals,
      including baseline venous oxygenation (Yv ), cerebrovascular reactivity (CVR),
      resting state BOLD fluctuation amplitude (RSFA), and baseline cerebral blood flow
      (CBF). This study sought to directly compare the modulation effects of these
      indices in the same fMRI session. The physiologic parameters were measured with
      techniques comparable with those used in the previous studies except for CBF,
      which was determined globally with a velocity-based phase-contrast MRI (instead
      of arterial-spin-labeling MRI). Using an event-related, scene-categorization fMRI
      task, we showed that the fMRI signal amplitude was positively correlated with CVR
      (P < 0.0001) and RSFA (P = 0.002), while negatively correlated with baseline Yv
      (P < 0.0001). The fMRI-CBF correlation did not reach significance, although the
      (negative) sign of the correlation was consistent with the earlier study.
      Furthermore, among the physiologic modulators themselves, significant
      correlations were observed between baseline Yv and baseline CBF (P = 0.01), and
      between CVR and RSFA (P = 0.05), suggesting that some of the modulators may
      partly be of similar physiologic origins. These observations as well as findings
      in recent literature suggest that additional measurement of physiologic
      modulator(s) in an fMRI session may provide a practical approach to control for
      inter-subject variations and to improve the ability of fMRI in detecting disease
      or medication related differences. Hum Brain Mapp 34:2078-2088, 2013. (c) 2011
      Wiley Periodicals, Inc. 

PMID- 22461236
TI  - Synthesis of ferrocenestrone: the first metallocene based steroid analogue.
AB  - Ferrocenestrone, the first steroid derivative containing a metallocene moiety,
      was stereoselectively prepared. The key steps included the enantioselective
      functionalization of ferrocene, elongation of the side chain, intramolecular
      enyne metathesis, Diels-Alder reaction, heterogeneous hydrogenation of the
      sterically hindered double bond, and finally inversion of the configuration at
      C13.

PMID- 22461237
TI  - Polarization properties of a CdSe/ZnS and Au nanoparticle dimer.

PMID- 22461238
TI  - Three-dimensional electrospun alginate nanofiber mats via tailored charge
      repulsions.
AB  - The formation of 3D electrospun mat structures from alginate-polyethylene oxide
      (PEO) solution blends is reported. These unique architectures expand the
      capabilities of traditional electrospun mats for applications such as
      regenerative medicine, where a scaffold can help to promote tissue growth in
      three dimensions. The mat structures extend off the surface of the flat collector
      plate without the need of any modifications in the electrospinning apparatus, are
      self-supported when the electric field is removed, and are composed of bundles of
      nanofibers. A mechanism for the unique formations is proposed, based on the fiber
      fiber repulsions from surface charges on the negatively charged alginate.
      Furthermore, the role of the electric field in the distribution of alginate
      within the nanofibers is discussed. X-ray photoelectron spectroscopy is used to
      analyze the surface composition of the electrospun nanofiber mats and the data is
      related to cast films made in the absence of the electric field. Further
      techniques to tailor the 3D architecture and nanofiber morphology by changing the
      surface tension and relative humidity are also discussed.

PMID- 22461239
TI  - A catalytic multicomponent approach for the stereoselective synthesis of cis-4,5
      disubstituted pyrrolidinones and tetrahydro-3H-pyrrolo[3,2-c]quinolines.

PMID- 22461240
TI  - Coping in long-term survivors of childhood cancer: relations to psychological
      distress.
AB  - OBJECTIVE: The goal of this study was to describe coping strategies and their
      associations with psychological distress in young adult survivors of childhood
      cancer. METHODS: One hundred and sixty-four childhood cancer survivors, at least
      7 years after diagnosis, completed questionnaires assessing demographics, health
      information, psychological distress, and different ways of coping (return rate:
      61%). The Brief Symptom Inventory-18 (BSI-18) and the Post-traumatic Diagnostic
      Scale's (PDS) eight-item short form were used to measure psychological distress.
      Coping was assessed with the Cognitive Control Strategies Scale (CCSS), the
      Illness Perception Questionnaire-Revised (IPQ-R), and the White Bear Suppression
      Inventory (WBSI). RESULTS: Higher levels of distress were associated with the
      female sex, not being in a relationship, and with the presence of medical late
      effects. These predictors explained 12% of the variance in psychological
      distress. When coping variables were also entered into the equation, the amount
      of explained variance increased to 50%. The most important determinants of
      psychological distress in our sample were a tendency to suppress negative
      thoughts and a low level of optimism. CONCLUSION: These results contribute to a
      better understanding of the correlates of difficulties in long-term psychological
      adjustment after childhood cancer. Cognitive strategies, which are associated
      with or may increase the risk for concurrent psychological distress, in specific,
      avoidance of negative thoughts and a lack of positive future expectations, should
      be addressed in psychological counseling with survivors suffering from symptoms
      of distress.

PMID- 22461241
TI  - Whispering gallery mode aptasensors for detection of blood proteins.
AB  - Whispering gallery mode resonators (WGMR), as silica microspheres, have been
      recently proposed as an efficient tool for the realisation of optical biosensors.
      In this work we present a functionalization procedure based on the DNA-aptamer
      sequence immobilization on WGMR, able to recognize specifically thrombin or VEGF
      protein, preserving a high Q factor. The protein binding was optically
      characterized in terms of specificity in buffer solution or in 10% diluted human
      serum. Simulation of the protein flow was found in good agreement with
      experimental data. The aptasensor was also chemically regenerated and tested
      again, demonstrating the reusability of our system.

PMID- 22461242
TI  - Neural response to emotional stimuli during experimental human endotoxemia.
AB  - Increases in peripheral cytokines during acute inflammation may affect various
      neuropsychological functions. The aim of this functional magnetic resonance
      imaging (fMRI) study was to investigate the effects of acute endotoxemia on mood
      and the neural response to emotionally aversive visual stimuli in healthy human
      subjects. In a double-blind, randomized crossover study, 18 healthy males
      received a bolus injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or
      saline. Plasma levels of pro- and anti-inflammatory cytokines and cortisol as
      well as mood ratings were analyzed together with the blood-oxygen-level dependent
      (BOLD) response during the presentation of aversive versus neutral pictures.
      Endotoxin administration induced pronounced transient increases in plasma levels
      of TNF-alpha, IL-1ra, IL-6, IL-10, and cortisol. Positive mood was decreased and
      state anxiety increased. In addition, activation of right inferior orbitofrontal
      cortex (OFC) in response to emotional visual stimuli was significantly increased
      in the LPS condition. Increased prefrontal activation during the presentation of
      emotional material may reflect enhanced cognitive regulation of emotions as an
      adaptive response during an acute inflammation. These findings may have
      implications for the putative role of inflammatory processes in the
      pathophysiology of depression.

PMID- 22461243
TI  - High-performance transistors and complementary inverters based on solution-grown
      aligned organic single-crystals.

PMID- 22461244
TI  - From the Editor-in-Chief.

PMID- 22461245
TI  - Implementing adherence to osteoporosis treatments.
AB  - At present chronic diseases are of crucial importance for all health services in
      the Western World for both their epidemic prevalence and the fact that they
      absorb a growing proportion of health service financial resources. Osteoporosis
      has clinical and public health importance because osteoporotic fractures are one
      of the most common causes of disability and an important contributor to medical
      costs in many regions of the world Increased longevity has resulted in the
      emergence of age-related fragility fractures as a major public health problem.
      Today several classes of effective drugs are available for osteoporosis. However,
      these drugs to be effective, need to be taken long-term. In the case of BPs data
      have shown that nearly 70% of patients on a daily, and almost 60% on a weekly
      treatment, stop taking medication before the end of 1 year. A poor adherence is
      associated to an increased probability of fractures with consequent higher
      likelihood of hospitalisation and higher costs. Since reasons for nonadherence
      may depend on individual beliefs and circumstances the strategy to improve
      adherence should be tailored according to the individual patient. These findings
      underline the key role played by the physicians, above all GPs, in a strategy to
      improve adherence which now could be supported by the avaibility of new drugs and
      innovative administration routes.

PMID- 22461246
TI  - Advances in the surgical treatment of fragility fractures of the upper femur.
AB  - Fragility fractures typically occur in elderly patients. They are related to
      osteoporosis, because of the weakening of the bone structure, and are the result
      of low-energy injuries and often involve the metaphyseal segments of bone. The
      fracture of the upper extremity of the femur are one of the most typical of the
      elderly patients. They may be intracapsular (femoral neck fractures) or
      extracapsular (intertrochanteric fractures). Each kind of fracture can be treated
      in several ways: the intracapsular fracture can be treated with screws, unipolar
      or bipolar hemiarthroplasty or even with total arthroplasty. The extracapsular
      fractures instead can be treated with sliding hip screw, intramedullary nail,
      femoral neck screws, helical blade or primary arthroplasty. What must be
      remembered is that osteoporotic bone has distinct morphologic characteristics
      that influence its biomechanical properties and therefore the choices and
      techniques for internal fixation. Therefore only a complete understanding of the
      biology of the osteoporotic bone will lead to a good quality of the treatment of
      the fragility fractures.

PMID- 22461247
TI  - Vertebroplasty and balloon kyphoplasty in osteoporosis: friends or foes?
AB  - Osteoporotic vertebral fractures are a common cause of pain and disability and
      increased mortality in western countries. We have analyzed three studies about
      Vertebroplasty and Balloon Kyphoplasty that have been recently published. We
      discuss potential complications, results of each technique, and whether the long
      term outcome is similar in patients treated with Vertebroplasty and Balloon
      Kyphoplasty and non-surgical treatment, to decide the correct use of these
      minimally invasive techniques and for such patients.

PMID- 22461249
TI  - Magnesium disorders: clinical experience and review of the literature.

PMID- 22461250
TI  - The effects of exercise on bone. Basic concepts and implications for the
      prevention of fractures.
AB  - Osteogenic dynamic loads delivered to the skeleton during exercise prevent aging
      associated bone fragility. Moreover, because of its pleiotropic favourable
      effects on health, exercise improves quality of life, and specific types of
      exercise increase muscle strength, a known predictor of bone strength, and
      coordination and balance, and so reduce the risk of fallrelated fractures.
      Exercise should definitely be the mainstay of the prevention and treatment of
      osteoporosis; often however, physicians don't have enough know-how for
      evidencebased prescription of exercise. Moreover, the lack of facilities for safe
      implementation of the exercise programs compound the problem. Scientific
      societies and health authorities should invest in patient and physicians
      education about exercise and in promoting facilities (Gyms) devoted to training
      of persons with, or at risk of, metabolic diseases (osteoporosis, obesity,
      diabetes), like Metagym in Florence, Italy.

PMID- 22461248
TI  - Treatment options of secondary hyperparathyroidism (SHPT) in patients with
      chronic kidney disease stages 3 and 4: an historic review.
AB  - Secondary hyperparathyroidism (SHPT) is an early complication and a well-known
      factor negatively affecting cardiovascular mortality already in the late stages
      of chronic kidney disease (CKD). Negative effects can also be foreseen in early
      stages of CKD. AIM: Set against this background, I performed detailed clinical
      review of the specific literature from 1975 on the various types of trials used
      to treat SHPT in order to assess their effect on uremic patients affected by CKD
      stage 3 stage 4. RESULTS: Out of the 1,820 papers reviewed, I identified 14
      prospective controlled randomized trials involving in total 1,587 patients.
      Dietary approaches and the use of phosphorus chelating agents, either alone or in
      association, do not seem to be particularly promising for SHPT in uremic patients
      with CKD stage 3-4. Pending the publication of statistically wellstructured works
      on CKD stage 3-4, experience with calciummimetic agents in CKD stage 3-4 seems
      promising, even if there is a need to decrease the side effects most affecting
      medication compliance and as well safety calcium-mimetic agents seem to be more
      useful, especially in association with vitamin D derivatives. Further promising
      results seem to be provided by the latest generations of vitamin D derivatives
      such as paracalcitol which produces good SHPT control.

PMID- 22461251
TI  - Male osteoporosis and androgenic therapy: from testosterone to SARMs.
AB  - As in the women, male osteoporosis represents an important social problem,
      amplified by the increasing life expectance.Differently from women, 50% of male
      osteoporosis is secondary to treatments and/or diseases that make mandatory their
      search through an accurate clinical investigations in every newly diagnosed
      osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently
      undertreated, and too often it is revealed only after the occurrence of a
      fragility fracture. Androgens may prevent the loss of cancellous bone and
      stimulate periosteal cortical bone apposition. The anabolic effect of
      testosterone on both bone and muscle, is limited by the high incidence of
      androgenic side effects. Hypogonadism is the only situation where the benefits of
      the use of testosterone formulations exceed the side effects. Selective androgen
      receptor modulators can dissociate androgenic and anabolic effect on different
      tissues with various strategies. Many compounds have been studied with positive
      results in vivo and in clinical trials.

PMID- 22461253
TI  - Retrospective survey of clinical attention taken to osteoporosis in patients
      admitted in orthopaedic department for fragility fractures.
AB  - Considering that to international level it has put in evidence that often the
      diagnosis of osteoporosis is underestimated and that diagnostic and therapeutic
      attention of the same one are often neglected, the authors have assessed the
      degree of care provided by orthopaedic surgeons about the problem of
      osteoporosis, considering the medical files of orthopaedics department. Then
      corrective behaviour were proposed.

PMID- 22461252
TI  - Bone fragility and imaging techniques.
AB  - Bone fragility is a silent condition that increases bone fracture risk, enhanced
      by low bone mass and microarchitecture deterioration of bone tissue that lead to
      osteoporosis. Fragility fractures are the major clinical manifestation of
      osteoporosis.A large body of epidemiological data indicates that the current
      standard for predicting fragility fracture risk is an areal BMD (aBMD)
      measurement by DXA. Although mineral density measurements assess the quantity of
      bone, the quality of the tissue is an important predictor of fragility. Thus,
      bone strength is explained not only by BMD but also by macrostructural and
      microstructural characteristics of bone tissue. Imaging diagnostics, through the
      use of X-rays, DXA, Ultrasonography, CT and MR, provides methods for diagnosis
      and characterization of fractures, and semi- and quantitative methods for
      assessment of bone consistency and strength, that become precious for bone
      fragility clinical management if they are integrated by clinical risk factors.
      The last employment of sophisticated non-invasively imaging techniques in
      clinical research as high-resolution CT (hrCT), microCT (MU-CT), high-resolution
      MR (hrMR) and, microRM (MURM), combined with finite element analysis methods,
      open to new challenges in a better bone strength assessment to enhance the
      comprehension of biomechanical parameters and the prediction of fragility
      fractures.

PMID- 22461254
TI  - Idiopathic hypercalciuria and calcium renal stone disease: our cases.
AB  - Renal idiopathic stone disease affects about 8% of the Italian population. The
      most common form in western countries (70- 80% of the cases) is calcium
      nephrolithiasis, with stones formed mainly by calcium oxalate and phosphate. One
      of the main metabolic anomalies that is often associated with calcium
      nephrolithiasis is hypercalciuria. Primary hypercalciuria is a metabolic defect
      characterized by an increased renal calcium excretion. This metabolic alteration
      is present in the general population with a frequency of 5-10%, but can reach 45
      50% in subjects affected by nephrolithiasis. We studied 149 patients affected by
      idiopathic calcium nephrolithiasis.The aim of the present study was to evaluate
      the association between familiarity for nephrolithiasis and hypercalciuria in
      this population of patients.

PMID- 22461256
TI  - Prevention, diagnosis and treatment of osteoporosis following menopause induced
      due to oncological disease.
AB  - Owing to the improved effectiveness of the treatment protocols for oncological
      disease, in the last few years we have seen an increase in the number of women in
      iatrogenic menopause secondary to integrated oncological treatments or surgical,
      pharmacological or radiological therapies. Particularly if it is premature,
      menopause in these subjects, who are already strongly debilitated by the primary
      pathology, may have heavy physical and psychic repercussions on the quality of
      life.Particular attention must be paid to the prevention and treatment of
      osteoporosis, which is linked both to premature cessation of the reproductive
      capacity and to the treatments for the oncological disease, which may represent
      an additional risk for the development of premature, severe osteoporosis. Some
      oncological diseases involve therapies which affect bone metabolism. At the
      sametime, for example in breast cancer, some bone protective drugs like hormone
      replacement therapy are controindicated. The introduction for breast cancer of a
      new category of drugs, aromatase inhibitors, seems to be linked to an increase in
      bone fractures. Correct treatment of these subjects involves a multidisciplinary
      specialist approach which we believe can be created through a targeted menopause
      surgery, which would thus become the ideal place for the evaluation of problems
      linked to the treatment of cancer and the consequent early menopause.A targeted
      surgery like this allows us to create individual treatment paths with
      differentiated timing, and to address questions which are still unanswered, such
      as the risk of osteoporosis deriving from the effects of aromatase inhibitors on
      the bones, and the preventive effectiveness of the combination with
      bisphosphonates.

PMID- 22461255
TI  - Absorption and bioeffects of an isoflavone-based supplementation in
      postmenopausal women.
AB  - Epidemiological studies suggest that consumption of isoflavones rich diets can
      improve several postmenopausal complications. The aim of this study was to
      investigate the absorption and the efficacy of isoflavonic supplementation in the
      treatment of menopausal symptoms.36 postmenopausal women received 75 mg/day of
      isoflavones in the form of tablets, for six months. 21 subjects concluded the
      treatment. Plasmatic and urinary samples were collected before and after the
      treatment, along with a dietary interview. Isoflavones were determined in
      biological samples and in commercial administered supplements by a HPLC/DAD
      system.Results showed the presence of genistein (from 0.043 to 1.820 micromol/L)
      in plasma samples, and of genistein (from 2.486 to 20.363 micromol/24h) and
      daidzein (from 11.106 to 98.091 micromol/24h) in the urines of the treated women.
      In the 21 completers the Greene Climateric scale value for hot flushes changed
      from 3 to 1 or 0. No changes of the endometrial thickness and of the breast
      tissue were detected. The analysis of the supplement content in the tablets was
      in agreement with what declared by the producer.Administration of isoflavone
      supplements produced a decrease of symptoms in this cohort of postmenopausal
      women monitored for isoflavone absorption.

PMID- 22461257
TI  - Polyostotic form of fibrous dysplasia in a 13 years old Colombian girl showing
      clinical and biochemical response to neridronate intravenous therapy.
AB  - Fibrous dysplasia affects principally the bone, it might also comprise extra
      skeletal anomalies; whereby the bone is replaced by a dysplastic fibrous tissue.
      It is classified according to the number of affected bones, and its association
      to endocrine alterations in: monostotic, polyostotic forms and Albright's
      disease. A congenital etiology is suggested. Pathologic fractures are the most
      frequently associated complications. We present a case with a polyostotic form of
      fibrous dysplasia in a 13 years old Colombian girl, wherein a differential
      diagnosis and treatment decision was made.

PMID- 22461258
TI  - Teriparatide treatment in adult hypophosphatasia in a patient exposed to
      bisphosphonate: a case report.
AB  - We describe the case of a woman with hypophosphatasia previously exposed to
      bisphosphonate and subsequently treated with teriparatide (recombinant human PTH
      1-34).A Caucasian woman sustained bilateral femur stress fractures when she was
      fifty years old, which widened despite use of calcium, vitamin D and risedronate
      for 2.5 years and required intramedullary rods for stabilization.
      Hypophosphatasia was diagnosed in the interim due to low serum alkaline
      phosphatase (ALP) (ALP 20 IU/L; normal (N), 40-150 IU/L) and high pyridoxal 5'
      phosphate (3400 nmol/L; N 18-175 nmol/L). She was referred for further
      management. On presentation, she had significant fracture site pain and
      generalized bone pain (weight bearing and non-weight bearing) - making her walker
      dependent at home and wheel chair dependent outside home.She could not sleep at
      night due to discomfort when she moved. Daily teriparatide injections, 20 mcg
      subcutaneously were prescribed.At 8-weeks follow-up, fracture site pain, weight
      bearing and non weight-bearing pain improved significantly allowing ambulation
      for prolonged periods without assistance. She slept at night without discomfort.
      Improvement persisted during her entire treatment period. Radiographs taken at 4
      and 16 months of treatment demonstrated healing of femur fractures.Biochemically,
      mean urine cross-link-N-telopeptide increased 11% as compared to her base-line,
      while bone specific alkaline phosphatase did not increase as expected.In
      conclusion, we observed an uncoupling of bone formation and resorption markers
      during her treatment period in the face of notable clinical and radiological
      improvement. Off-label use of teriparatide may help patients with
      hypophosphatasia.

PMID- 22461259
TI  - Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1
      H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by
      recognition tunneling.
AB  - We have developed a chemical reagent that recognizes all naturally occurring DNA
      bases, a so called universal reader, for DNA sequencing by recognition tunneling
      in nanopores.1 The primary requirements for this type of molecules are the
      ability to form non-covalent complexes with individual DNA bases and to generate
      recognizable electronic signatures under an electrical bias. 1-H-imidazole-2
      carboxamide was designed as such a recognition moiety to interact with the DNA
      bases through hydrogen bonding. In the present study, we first furnished a
      synthetic route to 1-H-imidazole-2-carboxamide containing a short omega
      functionalized alkyl chain at its 4(5) position for its attachment to metal and
      carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide
      were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2
      carboxamide exists in a neutral form between pH 6-10. Density functional theory
      (DFT) and NMR studies indicate that the imidazole ring exists in prototropic
      tautomers. We propose an intramolecular mechanism for tautomerization of 1-H
      imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self
      associate to form hydrogen bonded dimers. NMR titration found that naturally
      occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through
      hydrogen bonding in a tendency of dG>dC?dT>dA. These studies are indispensable to
      assisting us in understanding the molecular recognition that takes place in the
      nanopore where routinely used analytical tools such as NMR and FTIR cannot be
      conveniently applied.

PMID- 22461260
TI  - Diffusion kurtosis imaging and log-normal distribution function imaging enhance
      the visualisation of lesions in animal stroke models.
AB  - In this work, we report a case study of a stroke model in animals using two
      methods of quantification of the deviations from Gaussian behaviour: diffusion
      kurtosis imaging (DKI) and log-normal distribution function imaging (LNDFI). The
      affected regions were predominantly in grey rather than in white matter. The
      parameter maps were constructed for metrics quantifying the apparent diffusivity
      (evaluated from conventional diffusion tensor imaging, DKI and LNDFI) and for
      those quantifying the degree of deviations (mean kurtosis and a parameter sigma
      characterising the width of the distribution). We showed that both DKI and LNDFI
      were able to dramatically enhance the visualisation of ischaemic lesions in
      comparison with conventional methods. The largest relative change in the affected
      versus healthy regions was observed in the mean kurtosis values. The average
      changes in the mean kurtosis and sigma values in the lesions were a factor of two
      to three larger than the relative changes observed in the mean diffusivity. In
      conclusion, the applied methods promise valuable perspectives in the assessment
      of stroke.

PMID- 22461262
TI  - A special conjugated model around sp3 carbon atoms: density functional theory
      study on the homoaromatic electron delocalization and applications of benzo-fused
      tetra(triptycene)porphyrins.
AB  - The three-unit homoaromatic electron-delocalizing nature of the benzo-fused
      tetra(triptycene)porphyrins (TTPs) with a three-dimensional conjugated model is
      clarified using density functional theory studies. Due to the electron
      delocalization, the unidirectional photon-induced current of this kind of TTP
      molecular skeleton with a highest efficiency of about 90% in the range between
      350 and 500 nm gives them great potential as efficient solar antenna collectors.
      In addition, their active triptycene cups fused at the central porphyrin core
      render possible potential application in host-guest chemistry.

PMID- 22461261
TI  - Size-dependent fracture mode transition in copper nanowires.
AB  - In situ uni-axial tensile tests of single-crystalline copper nanowires are
      performed using a micromechanical device inside a scanning electron microscope
      chamber. The single-crystalline copper nanowires are synthesized by solvothermal
      processes, and the growth direction along the wire axis is the <110> orientation
      as confirmed by transmission electron microscopy (TEM) selected area diffraction
      (SAD) analysis. The fracture strengths of copper nanowires are found to be much
      higher than that of bulk copper. More interestingly, both ductile and brittle
      like fracture modes are found in the same batch of fabricated nanowires, and the
      fracture modes appear to be dependent on the diameters of tested nanowires. From
      the analysis of fracture surfaces, sample morphologies and corresponding stress
      strain curves, the competition between deformation and fracture mechanisms
      controlled by initial defects density and by the probability of dislocation
      interactions is attributed to this intriguing size-dependent fracture mode
      transition.

PMID- 22461263
TI  - Development and validation of a measure of criminal social identity within a
      sample of Polish recidivistic prisoners.
AB  - BACKGROUND: Social identity is a well-established theoretical concept within
      psychological research; however, the role of criminal social identity has
      received far less research attention. One salient reason for the limited research
      relating to the concept of criminal social identity is the absence of a specific
      measure. AIM: To develop and test the construct validity of a new measure of
      criminal social identity (MCSI) and to provide additional evidence relating to
      Cameron's three-factor conceptualisation of social identity. METHOD: The eight
      item MCSI was used to collect data from recidivists incarcerated in high-security
      prison (N=312) to assess criminal social identification. These data were
      subjected to confirmatory factor analysis. RESULTS: Three alternative models of
      criminal social identity were specified and tested in Mplus 6, and results
      revealed that the data were best explained by a three-factor model of criminal
      social identity (cognitive centrality, in-group affect and in-group ties).
      CONCLUSION: The current study is important in terms of future research in
      criminology and psychology because the MCSI provides the first reliable MCSI,
      which was developed and validated on a relatively large recidivistic prison
      sample.

PMID- 22461264
TI  - Prevalence of equinus in diabetic versus nondiabetic patients.
AB  - BACKGROUND: There are no conclusive data to support the contention that diabetic
      patients have an increased frequency of ankle equinus compared with their
      nondiabetic counterparts. Additionally, a presumed contributing cause of foot
      ulceration is ankle joint equinus. Therefore, we sought to determine whether
      persons with diabetes have a higher prevalence of ankle joint equinus than do
      nondiabetic persons. METHODS: A prospective pilot survey of 102 outpatients (43
      diabetic and 59 nondiabetic) was conducted. Demographic and historical data were
      obtained. Each patient underwent a standard lower-extremity examination,
      including the use of a biplane goniometer to measure ankle joint range of motion.
      RESULTS: Equinus, defined as ankle dorsiflexion measured at 0 degrees  or less,
      was found in 24.5% of the overall population. In the diabetes cohort, 16 of 43
      patients (37.2%) were affected compared with 9 of 59 nondiabetic participants
      (15.3%) (P = .011). There was a threefold risk of equinus in the diabetic
      population (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.28-8.44; P <
      .013). The equinus group had a history of ulceration in 52.0% compared with 20.8%
      of the nonequinus group (P = .003). Equinus, therefore, imparted a fourfold risk
      of ulceration (OR, 4.13; 95% CI, 1.58-10.77; P < .004). We also found a 2.8 times
      risk of equinus in patients with peripheral neuropathy (OR, 2.8; 95% CI, 1.11
      7.09; P < .029). CONCLUSIONS: Equinus may be more prevalent in diabetic patients
      than previously reported. Although we cannot prove causality, we found a
      significant association between equinus and ulceration.

PMID- 22461265
TI  - Controlled release of epidermal growth factor from hydrogels accelerates wound
      healing in diabetic rats.
AB  - BACKGROUND: We sought to develop new recombinant human epidermal growth factor
      (rhEGF)-containing hydrogels and to investigate their biological activity and
      therapeutic effects on wound healing in diabetic rats. METHODS: Levels of rhEGF
      released from hydrogels were measured by enzyme-linked immunosorbent assay. The
      cellular proliferating activity of released rhEGF was evaluated by MTT assay.
      Fifty-six wounded diabetic rats were randomly divided into four groups with
      different topical treatment daily. The therapeutic effects were evaluated by
      wound area measurement, histologic analysis, immunohistochemical assessment of
      proliferating cell nuclear antigen and B-cell lymphoma/leukemia-2, and Western
      blotting of EGF receptor. RESULTS: The rhEGF released from the hydrogel matrix
      kept its bioactivity on stimulating proliferation of the BALB/c3T3 cell line.
      Wound closure rates on postoperative day 14 were 75.8% in the negative control
      group, 82.83% in the group treated with hydrogel matrix, 85.87% in the group
      treated with rhEGF-containing hydrogel, and 81.18% in the group treated with
      rhEGF solution. Compared with hydrogel matrix, rhEGF-containing hydrogel had an
      additional effect on induction of EGF receptor expression (P < .05). Compared
      with negative controls, protein expression of B-cell lymphoma/leukemia-2 was
      higher in the rhEGF-containing groups (P < .05). Proliferating cell nuclear
      antigen was induced at its highest level on day 7 in the rhEGF-containing
      hydrogel-treated group (P < .05). CONCLUSIONS: These data from in vitro release
      and diabetic animal models highlight the efficacy of hydrogels as a controlled
      releasing system for topical application of EGFs. The rhEGF-containing hydrogel
      we developed holds the merits of prolonged and sustained releasing of bioactive
      rhEGF and therapeutic potential in enhancing diabetic wound healing.

PMID- 22461266
TI  - Complex regional pain syndrome of the pediatric lower extremity: a retrospective
      review.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) type 1 is a disorder of the
      extremities characterized by pain, edema, limited range of motion, integument
      changes, and vasomotor instability often after an inciting event. In the
      pediatric population, CRPS may be misdiagnosed, or missed entirely, as CRPS
      literature for this patient population is lacking. METHODS: Twenty-seven
      pediatric patient medical records with the diagnosis of CRPS type 1 from the
      institutional and private practices of the principal investigator (E.J.H.) were
      reviewed for demographics, inciting event, lower-extremity clinical examination,
      ancillary testing, previous treatments, time to diagnosis, treatment after
      diagnosis, and time to resolution of symptoms. RESULTS: Females composed 85.2% of
      the patient population (n = 23) (mean age of females, 11.11 years). An inciting
      event preceded pain in 74.1% of patients (n = 20). On physical examination, more
      than 50% of patients were identified as having changes in skin color and
      temperature, edema to the affected lower extremity, painful or decreased range of
      motion in affected joints, and intact lower-extremity motor function. The average
      time to resolution of symptoms was 6.8 weeks for the entire population.
      CONCLUSIONS: Diagnosis of CRPS type 1 should be considered in a preadolescent
      female complaining of pain out of proportion after an inciting event with a
      physical examination demonstrating change in skin color, decrease in skin
      temperature, edema, and painful or diminished range of motion in affected joints.
      Prompt diagnosis can decrease the time to resolution of symptoms.

PMID- 22461267
TI  - Radiographic measurement of the first metatarsal: a new technique to improve the
      accuracy of intermetatarsal angle measurement.
AB  - BACKGROUND: The first intermetatarsal angle is a radiographic measurement
      frequently used in hallux valgus surgery. A plethora of techniques to obtain the
      angle exist, but no standardized technique is used to obtain the bisection of the
      first metatarsal. A novel technique, the Taylor-Metcalfe technique, has been
      developed and compared with two existing methods to identify the repeatability
      and reproducibility of the first metatarsal bisection. METHODS: To evaluate the
      measurement accuracy of the novel technique, we calculated the intraobserver and
      interobserver coefficients for the three techniques with 30 preoperative and 30
      postoperative radiographs. RESULTS: The intraobserver coefficient of
      repeatability for the preoperative and postoperative measurements ranged from 2.1
      to 4.4, with the novel technique obtaining the lowest values. The novel technique
      also obtained the lowest values for interobserver reproducibility, with values
      obtained ranging from 0.77 to 1.61. An existing technique had the lowest value
      for interobserver reproducibility for preoperative measurements, with the novel
      technique obtaining the lowest values for the remaining measurements.
      CONCLUSIONS: Compared with two existing techniques, a novel technique for
      accurately obtaining the bisection of the first metatarsal was consistently found
      to be reproducible and repeatable.

PMID- 22461268
TI  - Epidemiologic factors affecting plantar arch development in children with flat
      feet.
AB  - BACKGROUND: Foot problems are reported by approximately 70% to 80% of adults and
      30% of children. One of the most important characteristics affecting its
      incidence is medial longitudinal arch. Assessing arch height provides valuable
      information for prescribing appropriate footwear that reduces the consequences of
      flatfoot. The main goals of this study were to explore epidemiologic factors that
      affect arch height and to predict arch height in children with flatfoot based on
      five variables using widely accessible, low-cost tools. METHODS: This study
      examined plantar arch height in 80 children with flatfoot aged 7 to 15 years. The
      evaluation criteria included low arch height, correct knee and heel position, and
      correct body symmetry. To measure arch height, the children sat in a chair and
      placed their feet on level ground. A caliper was used to measure the height
      between the bottom of the navicular tuberosity and the floor. Using least mean
      square error scheme, a multivariable model was fitted to the plantar arch height
      for all of the participants using independent variables, including age, Cole
      index, sex, place of residence, and physical activity. RESULTS: Arch height
      increased as age increased in boys and girls in rural and urban areas. A
      significant increase in arch height occurred in 12- to 15-year-old boys and 10-
      to 15-year-old girls. In boys, arch height was 30% lower than in girls (P = .05).
      In children in cities, arch height was lower by 26% than in children in rural
      areas (P = .05). Arch height increased by 41.8% in inactive boys and by 115.2% in
      inactive girls in rural areas. It was reduced by 59.4% in boys and by 47.4% in
      girls as the Cole index increased from 82.2 to 152.0. The suggested model
      predicted arch height using the child's age, Cole index, sex, place of residence,
      and physical activity (r > 0.97, error < 0.04 mm [2%], P < .05). CONCLUSIONS:
      Flat feet in children may be affected by age, sex, Cole index, place of
      residence, and physical activity. The proposed model allows plantar arch heights
      in children with flat feet to be predicted without the need for sophisticated
      technology via controlling the child's weight and physical activity for
      prescribing appropriate footwear.

PMID- 22461269
TI  - Intratest reliability in determining the subtalar joint axis using the palpation
      technique described by K. Kirby.
AB  - BACKGROUND: Exact determination and classification of the spatial position of the
      subtalar joint axis could be a predictive clinical variable in biomechanical
      analysis and a valuable tool in the design of functional foot orthoses. METHODS:
      Three clinicians with different levels of experience determined and classified
      the subtalar joint axis location, three times, on 52 individuals, using the
      clinical palpation, allocation and interpretation technique, as described by K.
      Kirby. RESULTS: High intratester precision (ICC 0.72 to 0.93) was found for
      determining the axis location (SEM, 3.72 degrees  for angle/0.27 cm for X-axis);
      however, classification of the spatial position of the axis has large intertester
      variation (kappa = 0.243 to 0.494) CONCLUSIONS: The clinical palpation technique
      itself is reliable; the consistent attribution of a classification, in other
      words, interpretation, is weak.

PMID- 22461270
TI  - Dynamic footprint measurement collection technique and intrarater reliability:
      ink mat, paper pedography, and electronic pedography.
AB  - BACKGROUND: Identifying the variability of footprint measurement collection
      techniques and the reliability of footprint measurements would assist with
      appropriate clinical foot posture appraisal. We sought to identify relationships
      between these measures in a healthy population. METHODS: On 30 healthy
      participants, midgait dynamic footprint measurements were collected using an ink
      mat, paper pedography, and electronic pedography. The footprints were then
      digitized, and the following footprint indices were calculated with photo digital
      planimetry software: footprint index, arch index, truncated arch index, Chippaux
      Smirak Index, and Staheli Index. Differences between techniques were identified
      with repeated-measures analysis of variance with post hoc test of Scheffe. In
      addition, to assess practical similarities between the different methods,
      intraclass correlation coefficients (ICCs) were calculated. To assess intrarater
      reliability, footprint indices were calculated twice on 10 randomly selected ink
      mat footprint measurements, and the ICC was calculated. RESULTS: Dynamic
      footprint measurements collected with an ink mat significantly differed from
      those collected with paper pedography (ICC, 0.85-0.96) and electronic pedography
      (ICC, 0.29-0.79), regardless of the practical similarities noted with ICC values
      (P = .00). Intrarater reliability for dynamic ink mat footprint measurements was
      high for the footprint index, arch index, truncated arch index, Chippaux-Smirak
      Index, and Staheli Index (ICC, 0.74-0.99). CONCLUSIONS: Footprint measurements
      collected with various techniques demonstrate differences. Interchangeable use of
      exact values without adjustment is not advised. Intrarater reliability of a
      single method (ink mat) was found to be high.

PMID- 22461271
TI  - Clinical efficacy and safety of tapentadol immediate release in the postoperative
      setting.
AB  - The appropriate treatment for postoperative pain remains a common dilemma for
      podiatric surgeons and patients undergoing surgery of the foot and ankle. The
      treatment of moderate to severe acute pain typically relies heavily on the use of
      opioid analgesics, such as hydrocodone and oxycodone, which are often associated
      with adverse effects, including nausea and vomiting. These adverse effects may
      have a negative impact on postoperative outcomes and reduce patient compliance
      with analgesic therapy. Tapentadol is a novel, centrally acting analgesic with
      two mechanisms of action--MU-opioid receptor agonism and norepinephrine reuptake
      inhibition--in a single molecule. Tapentadol immediate release has been evaluated
      in a series of clinical trials in patients with postoperative pain after
      bunionectomy. The results of these studies demonstrate that tapentadol immediate
      release is associated with an improved gastrointestinal tolerability profile
      relative to oxycodone immediate release at doses providing comparable analgesia.
      Therefore, tapentadol immediate release may offer an improved analgesic option
      for the relief of postoperative pain after podiatric surgery.

PMID- 22461272
TI  - Normal genetic variation of the human foot: Part 2: Population variance,
      epigenetic mechanisms, and developmental constraint in function.
AB  - Congenital deformities of the foot have been reported to correlate with
      regulatory epigenetic mechanisms that are also responsible for the timing and
      sequencing of developmental growth of the lower limb. Developmental variance of
      normal morphologic features has also been shown to vary between populations
      despite the retention of human foot characteristics. The molecular evidence for
      genetically controlled expressions of common evolved physical features is highly
      suggestive of regulatory control mechanisms that act together with developmental
      constraints to homogenize the retained functional characteristics of the foot.
      Genetic variance in morphologic features and functional plasticity when linked to
      morphometric change during gait may prove influential in clarifying kinematic and
      kinetic relationships.

PMID- 22461273
TI  - Synovial sarcoma of the anterior tibialis tendon.
AB  - We report the clinical features, radiographic findings, management and results of
      a patient with a post-traumatic synovial sarcoma of the anterior tibialis tendon.
      Our patient was managed operatively and with radiotherapy with good clinical
      results. No evidence of recurrence or metastatic disease was seen at 3-year
      follow-up.

PMID- 22461274
TI  - Charcot arthropathy of the first metatarsophalangeal joint.
AB  - Charcot arthropathy is an acute or subacute, often indolent, non-infectious or
      tumorous osteoarticular destruction of weightbearing skeletal structures in
      patients with reduced pain perception due to peripheral neuropathy. The authors
      present a rare case of progressive Charcot arthropathy of the first
      metatarsophalangeal joint with accompanying ulcer and foot deformity due to
      peripheral neuropathy. An arthrodesis of the first metatarsophalangeal joint with
      resection of the hypertrophic bone and osteophytes using a locking plate was
      performed. Also a condylectomy of the base of the proximal phalanx digitus II and
      III as well as a shortening osteotomy of the third metatarsal were conducted. The
      ulcer was debrided and primarily closed by suture. Mobilization was performed
      without weightbearing in a postoperative shoe for 6 weeks, the ulcer was
      completely healed and the arthrodesis had fused. Owing to the complexity of
      Charcot arthropathy careful preoperative evaluation, timing and dimension of
      surgery as well as treatment of associated comorbidities and sufficient
      postoperative care is important to reduce the complication rate and improve long
      term results.

PMID- 22461275
TI  - Surfer's toe: trauma-induced idiopathic acro-osteolysis in the toes of a 46-year
      old surfer: a case report.
AB  - Acquired acro-osteolysis (AOL) is defined as the resorption of bone from the
      tufts or shafts of the terminal phalanges. Acquired acro-osteolysis can manifest
      as a primary osteolysis syndrome and also appears in a number of disease states
      including rheumatologic disorders, neuropathic diseases, the result of prolonged
      exposure to polyvinyl chloride, and in rare cases, as a response to repeated
      mechanical stress. In this report, a 46-year-old surfer was evaluated for AOL as
      a complication of sports-related repetitive trauma to the right second and third
      toes. Radiography showed the bony tips of his right second and third toes had
      been eroded away. Acquired acro-osteolysis in the surfer's toes resulted from
      increased blood flow initiated to repair microdamage caused by repeated trauma to
      the distal ends of his second and third right toes due to the habitual dragging
      of the affected toes across a surfboard. The always initial lytic phase of bone
      repair was magnified by the increased arterial input to warm the extremities
      after prolonged exposure to cold. At 6-years' follow-up, the use of a protective
      bandage while surfing has permitted full regeneration of the affected toes.

PMID- 22461276
TI  - Treatment of mild, moderate, and severe onychomycosis using 870- and 930-nm light
      exposure: some follow-up observations at 270 days.
AB  - We have previously reported the results of a clinical trial in which the Noveon
      laser was used to treat onychomycosis. In the 180-day follow-up therein it was
      noted that positive clinical impact was demonstrable by a clearly measurable
      decrease in positive fungal culture and a concomitant decrease in positive
      microscopy with periodic acid-Schiff-stained nail scrapings. Review of 270-day
      mycological data, which are now available, confirmed that there was further
      decrease in both measures. Indeed, 38% of the treated population had negative
      culture and microscopy, qualifying as "mycological cures." These mycological
      cures occurred in cases categorized as mild, moderate, and even severe disease.

PMID- 22461277
TI  - A historical and current analysis for the DPM acquiring an MD or DO degree and an
      unrestricted medical license.
AB  - The podiatric medical profession has evolved substantially in the past 80 years.
      This evolution includes major changes in scope, in the requirements necessary to
      enter a podiatric medical school, and in the curriculum that must be completed to
      earn the degree of Doctor of Podiatric Medicine. Entrance requirements to the
      schools are now identical to the prerequisites for admission to MD and DO
      institutions, and licensure requires the completion of graduate medical
      education. Much of the curriculum also is the same as it is in MD and DO schools.
      In the past decade, discussion focusing on the ability of the DPM to acquire the
      MD or DO degree has intensified. An analysis is provided using a historical
      context regarding this potential initiative.

PMID- 22461279
TI  - Genetically encoded pH sensor for tracking surface proteins through endocytosis.
AB  - Traffic cam: a tandem dye prepared from a FRET acceptor and a fluorogenic donor
      functions as a cell surface ratiometric pH indicator, which upon internalization
      serves to follow protein trafficking during endocytosis. This sensor was used to
      analyze agonist-dependent internalization of beta(2)-adrenergic receptors. It was
      also used as a surrogate antigen to reveal direct surface-to-endosome antigen
      transfer between dendritic cells (not shown).

PMID- 22461278
TI  - Functional imaging of the hemodynamic sensory gating response in schizophrenia.
AB  - The cortical (auditory and prefrontal) and/or subcortical (thalamic and
      hippocampal) generators of abnormal electrophysiological responses during sensory
      gating remain actively debated in the schizophrenia literature. Functional
      magnetic resonance imaging has the spatial resolution for disambiguating deep or
      simultaneous sources but has been relatively under-utilized to investigate
      generators of the gating response. Thirty patients with chronic schizophrenia
      (SP) and 30 matched controls participated in the current experiment. Hemodynamic
      response functions (HRFs) for single (S1) and pairs (S1 + S2) of identical
      ("gating-out" redundant information) or nonidentical ("gating-in" novel
      information) tones were generated through deconvolution. Increased or prolonged
      activation for patients in conjunction with deactivation for controls was
      observed within auditory cortex, prefrontal cortex, and thalamus in response to
      single tones during the late hemodynamic response, and these group differences
      were not associated with clinical or cognitive symptomatology. Although patient
      hyperactivation to paired-tones conditions was present in several regions of
      interest, the effects were not statistically significant for either the gating
      out or gating-in conditions. Finally, abnormalities in the postundershoot of the
      auditory HRF were also observed for both single and paired-tones conditions in
      patients. In conclusion, the amalgamation of the entire electrophysiological
      response to both S1 and S2 stimuli may limit hemodynamic sensitivity to paired
      tones during sensory gating, which may be more readily overcome by paradigms that
      use multiple stimuli rather than pairs. Patient hyperactivation following single
      tones is suggestive of deficits in basic inhibition, neurovascular abnormalities,
      or a combination of both factors.

PMID- 22461280
TI  - Gallium hydride complexes stabilised by multidentate alkoxide ligands: precursors
      to thin films of Ga2O3 at low temperatures.
AB  - The donor-functionalised alkoxides {Me(3-x)N(CH(2)CH(2)O)(x)} (L(x); x = 1, 2)
      have been used to form gallium hydride complexes [{GaH(2)(L(1))}(2)] and
      [{GaH(L(2))}(2)] that are stable and isolable at room temperature. Along with a
      heteroleptic gallium tris(alkoxide) complex [Ga(L(1))(3)] and the dimeric complex
      [{GaMe(L(2))}(2)], these compounds have been used as single-source precursors for
      the deposition of Ga(2)O(3) by aerosol-assisted chemical vapour deposition
      (AACVD) with toluene as solvent. The resulting films were mostly transparent,
      indicating low levels of carbon contamination, and they were also mainly
      amorphous. However, [Ga(L(1))(3)] did contain visibly crystalline material
      deposited at a substrate temperature of 450  degrees C, by far the lowest ever
      observed for the CVD of gallium oxide.

PMID- 22461282
TI  - From the Editor-in-Chief.

PMID- 22461281
TI  - More single-nucleotide mutations surround small insertions than small deletions
      in primates.
AB  - Early studies have shown that single-nucleotide mutation rates increase close to
      insertions and deletions, but it is not fully understood how natural selection
      shapes genome-wide patterns of indels and their nearby single-nucleotide
      mutations. In this study, we find that, in primates, more single-nucleotide
      mutations surround small insertions than small deletions. This pattern affects
      <150 base pair (bp) sequences close to indels and persists under different
      genomic properties, such as exon/intron/intergenic contexts, repeated/nonrepeated
      sequences, replication timing, recombination rates, indel density, and guanine
      cytosine (GC) content. We propose two different, but not mutually exclusive,
      hypothetical mechanisms to explain the pattern. One mechanism is that the
      sequence context preferring insertion formation may also favor nucleotide
      substitutions. Another mechanism is related to a hypothesis in which indel
      heterozygosity tends to increase nearby nucleotide substitution rates. It means
      that if insertions spend more time in heterozygotes, insertions may accumulate
      more surrounding single-nucleotide changes. In conclusion, we characterize a
      special genome-wide evolutionary pattern for indels and nearby single-nucleotide
      changes. This pattern may be driven by natural selection and bias primates'
      genome evolution and phenotypic variations.

PMID- 22461283
TI  - Can an anti-fracture agent heal fractures?
AB  - Anti-fracture agents typically prevent fractures by augmenting bone mass and
      enhancing skeletal integrity. These agents exert their effects by means of anti
      catabolic or anabolic actions. Because fracture healing involves bone formation
      as well as bone resorption, it is reasonable to hypothesize that agents that
      affect these activities may also modulate skeletal repair. Bisphosphonates,
      agents that inhibit bone resorption, may enhance the healing of fractures or
      permit patients with fractures to bear weight earlier by delaying the conversion
      of calcified cartilage to woven bone, or woven bone to lamellar bone. In doing
      so, they increase the size of the fracture callus and small increases in the
      radius of fracture callus can have dramatic positive effects on fracture callus
      stiffness and strength. Another possibility is that certain hypertrophic
      nonunions fail to unite because of excessive remodeling of the callus. Use of a
      bisphosphonate may modulate this catabolic activity, uncouple it from the
      associated bone formation and promote healing. Inhibitors of RANKL have undergone
      far less investigation but may also act on osteoclast precursors to down-regulate
      bone resorption. Parathyroid hormone may enhance fracture repair by promoting
      chondrogenesis early in the healing process and osteogenesis at a later time. The
      former effect improves callus geometry while the latter effect improves bone
      quality as well as quantity. Several anecdotal reports and one randomized,
      controlled trial have suggested that parathyroid may enhance skeletal repair in
      specific clinical settings.Although these reports are based on solid scientific
      data, there are limited clinical data at this time. The use of anti-fracture
      agents for the enhancement of fracture healing will ultimately depend upon high
      quality evidence from well-designed, well-controlled clinical trials.

PMID- 22461284
TI  - Parameters for defining efficacy in fracture healing.
AB  - Complications of the bone-healing process, especially in elderly, osteoporotic
      patients, are cause of important medical and economical burden. At the same time,
      there is no clinical study today to have shown the efficacy of a pharmacological
      treatment to enhance fracture repair. The author analyzes the potential criteria
      that could be used for the evaluation of treatment efficacy to enhance fracture
      healing in the frame of a clinical study.

PMID- 22461285
TI  - Mechanism of action of strontium ranelate: what are the facts?

PMID- 22461286
TI  - Risedronate's efficacy: from randomized clinical trials to real clinical
      practice.
AB  - Osteoporosis represents the most common human bone disorder with a large medical
      and economical burden on the Health Care System. Bisphosphonates are the major
      drugs used for the treatment of osteoporosis. Differences in their chemical
      structures and pharmacokinetic actions can explain the different clinical
      efficacy among these molecules. Risedronate is a potent inhibitor of farnesyl
      pyrophosphate synthase, but does not bind strongly to mineral; this lower mineral
      binding may enable risedronate to have a wider distribution in bone. Its
      antifracture efficacy has been established in several randomized phase III
      controlled studies that showed its value in the reduction of vertebral, non
      vertebral and hip fractures. Randomized controlled trials and observational
      studies demonstrated risedronate efficacy and safety in different subsets of
      patients, therefore risedronate is configured, among oral therapies currently
      available for osteoporosis, as a drug of first choice.

PMID- 22461287
TI  - Efficacy of ibandronate: a long term confirmation.
AB  - Data deriving from randomized clinical trials, observational studies and meta
      analyses, including treatment regimens unlicensed for use in clinical practice,
      clearly support that 150 mg once-monthly oral and 3 mg quarterly i.v. doses of
      ibandronate are associated with efficacy, safety and tolerability; notably both
      these marketed regimens, which largely correspond to ACE >=10.8 mg, may in
      addition provide a significant efficacy on non-vertebral and clinical fracture
      (Fx) efficacy. The MOBILE and the DIVA LTE studies confirmed a sustained efficacy
      of monthly oral and quarterly i.v. regimens respectively, over 5 years.
      Furthermore, improved adherence rates with monthly ibandronate, deriving from
      studies evaluating large prescription databases, promise to enhance fracture
      protection and decrease the social and economic burden of postmenopausal
      osteoporosis.

PMID- 22461288
TI  - Periprosthetic bone density as outcome of therapeutic response.
AB  - The bone surrounding a prosthetic implant normally experiences a progressive
      quantitative reduction as a result of stress shielding and wear debris
      production, that can lead to the aseptic loosening of the implant. Dual-energy X
      ray absorptiometry (DXA), using software algorithms, can ensure a surrogate
      measure of load redistribution after the implant of the prosthetic components and
      can be a valid tool to evaluate the efficacy of pharmacological therapy to reduce
      the periprosthetic bone loss. In several animal and human studies DXA has been
      able to quantify antiresorptive action of bisphosphonates in the periprosthetic
      area.

PMID- 22461289
TI  - Surgical prosthetic treatment.
AB  - Fragility fractures typically occur in elderly patients related principally to
      osteoporosis. A significative percentage of these fractures have to be treated
      surgically but comorbilities are often present, and need to be grossly stabilized
      before surgery. However, there is for these fractures a high rate of morbidity
      and mortality at short-term. Moreover, patients affected by a fragility fracture
      are at risk for another fragility fracture later in life.The Authors present an
      overview of the main patterns of proximal femoral fractures, underlining the
      peculiar features and choices of surgical treatment, and relating to specific
      indications and results of each treatment.

PMID- 22461290
TI  - Percutaneous vertebroplasty: the radiologist's point of view.
AB  - INTRODUCTION: Vertebral compression fractures (VCFs), usually caused by
      osteoporosis, is a disabling pathology associated with back pain, low quality of
      life and high costs. We report a retrospective study of 852 patients who
      underwent Percutaneous Vertebroplasty (PVP) in our department, for treatment of
      refractory back pain caused by osteoporotic vertebral fractures. OBJECTIVES: To
      evaluate the safety and the helpfulness of the PVP in vertebral osteoporotic
      fractures treatment and, particularly on durable pain reduction, mobility
      improvement and analgesic drugs need. MATERIALS AND METHODS: Follow-up analysis
      was made through a questionnaire filled by the patients before and after PVP (1-6
      months), designed to measure pain, ambulation capacity, ability to perform
      activities of daily living (ADL) and analgesic drugs administration. RESULTS: A
      statistically significant difference between visual analogue scale (VAS) values
      before and after treatment has been observed. No difference between VAS values
      were observed at 1 and 6 months post-treatment period. The treated vertebrae
      number did not influence post-treatment VAS values during all the follow-up.
      Ambulation capacity and the ability to perform ADL have been improved following
      PVP. Patients also reported significant reduction in administration of
      medications after PVP. CONCLUSIONS: PVP is a safe and useful procedure in painful
      osteoporotic VCFs treatment, able to reduce pain, improve patients mobility and
      decrease analgesic drugs need.

PMID- 22461291
TI  - Rehabilitation in osteoporotic vertebral fractures.
AB  - Vertebral fractures occur particularly in osteoporotic patients due to an
      increased bone fragility. Vertebral fractures influence the quality of life,
      mobility and mortality. Preventive training exercises and proprioception
      reeducation can be utilised for improving posture, balance and level of daily
      function and for decreasing pain. Quality of life is improved even beyond the
      active training period. This mini review provides information based on the
      literature for the rehabilitation of osteoporotic vertebral fractures after
      conservative or surgical treatment.

PMID- 22461292
TI  - Rehabilitation in peripheral non femoral fractures: a review.
AB  - This paper is a short review of the available information on peripheral non
      femoral fractures (PNFF) which are strictly related to osteoporosis. Particular
      attention is focused on wrist fractures in view of their frequent occurrence as
      indicated by world wide statistics. Of special interest is the definition of risk
      groups (old age), risk areas (developed countries) and risk factors. Reference is
      made to 2008 WHO guidelines for fracture risk assessment. PNFF are a serious
      concern to health authorities because their high incidence in constant growth,
      causes a serious burden on the health budget. The pathway of patient care is
      described, from initial evaluation (including bone fragility, multi-morbidity and
      risk factors) to specific diagnosis and treatment. The multiplicity of
      etiological factors involved requires multidisciplinary approach. This aspect
      justifies the importance given to rehabilitation, which is the longest part of
      patient care and is strictly connected to preventive measures. There is ample
      reference to falls, to exercises, to appropriate sports, to complications and to
      active and passive mobilization. The paper suggests research in areas related to
      PNFF, to health economics, epidemiology, prevention, health education, training
      and multidisciplinary coordination.

PMID- 22461294
TI  - Pharmaco-economic issues in the treatment of severe osteoporosis.
AB  - INTRODUCTION: clinical guidelines recommend to identify and treat people at high
      risk of fracture. METHODS: we have carried out a simulation concerning pharmaco
      economic issues in the treatment of severe osteoporosis and particularly those
      people with previous femoral fragility fractures, assuming that only 13.1% of hip
      fractured patients had started a proper antifracture therapy, as shown by the
      analysis of the Tuscany regional database. RESULTS: Annual costs sustained by the
      Italian healthcare system for treating hip fractured patients all over Italy have
      been estimated to range from 2 560 000 in year 2000 to 3 291 750 in year 2005,
      representing only 0,3% of the overall costs sustained because of hip fractures in
      Italy. CONCLUSIONS: Sixty percent of the pharmacological costs can be considered
      as ineffective from a therapeutic point of view because patients were assuming
      their drugs only for 6 months. There is a need for specific codification of
      osteoporotic fragility fractures at hospital admissions and for implementing
      regional strategies aimed to reduce hip re-fractures by increasing the number of
      patients on treatment and incrementing adherence to treatment.

PMID- 22461293
TI  - Kyphoplasty and vertebroplasty in the management of osteoporosis with subsequent
      vertebral compression fractures.
AB  - Osteoporosis with subsequent vertebral compression fractures (VCFs) is an
      increasingly common problem in western countries. This systematic review tries to
      update the evidence base for Balloon Kyphoplasty (BKP) and Vertebroplasty (PV) in
      the management of VCFs. We have analyzed 16 reviews and 97 articles. The majority
      of studies compares conventional medical management of VCFs to patients
      undergoing BKP or VP. We discuss selection criteria, techniques, potential
      complications, advantages and disadvantages, and results of each technique,
      recognizing that prospective, randomized controlled studies are necessary to
      objectively compare these techniques.

PMID- 22461295
TI  - Strontium Ranelate and bone healing: report of two cases.

PMID- 22461296
TI  - Intercoupling surface plasmon resonance and diffusion reflection measurements for
      real-time cancer detection.
AB  - Spatial diffusion reflection (DR) measurements of gold nanorods (GNR) were
      recently suggested as a simple and highly sensitive non-invasive and non-ionizing
      method for real-time cancer detection. In this paper we demonstrate that
      wavelength dependent DR measurements enable the spectral red-shift observation of
      highly concentrated GNR. By conjugating targeting moieties to the GNR, large
      density of GNR can specifically home onto cancer cells. The inter-particle
      plasmon resonance pattern of the highly concentrated GNR leads to an extension
      and a red-shift (Deltalambda) in the absorption spectrum of the concentrated GNR.
      Dark-field microscopy was used in order to measure the expected Deltalambda in
      different GNR concentrations in vitro. Double-wavelength DR measurements of
      tissue-like phantoms and tumor bearing mice containing different GNR
      concentrations are presented. We show that the DR profile of the highly
      concentrated GNR directly correlate with the spectral extension and red-shift.
      This presented work suggests that wavelength dependent DR method can serve as a
      promising tool for real-time superficial tumor detection.

PMID- 22461298
TI  - A quaterthiophene-based rotaxane: synthesis, spectroscopy, and self-assembly at
      surfaces.
AB  - Threaded molecular wires are shown to feature tunable properties. A new rotaxane
      based on a quaterthiophene threaded through a single beta-cyclodextrin exhibits
      delocalization of the aromatic system that is also extended onto the central
      phenyl rings of the m-terphenylene end-groups. The rotaxane can undergo self
      assembly that is better than the analogous bithiophene derivative, due to the
      increased pi-pi interactions.

PMID- 22461300
TI  - Yolk sac number does not predict reliably amnionicity in monochorionic twin
      pregnancies: a case of a monochorionic monoamniotic twin pregnancy with two
      distinct yolk sacs on early first-trimester ultrasound.

PMID- 22461299
TI  - A decisional space for fMRI pattern separation using the principal component
      analysis--a comparative study of language networks in pediatric epilepsy.
AB  - Atypical functional magnetic resonance imaging (fMRI) language patterns may be
      identified by visual inspection or by region of interest (ROI)-based laterality
      indices (LI) but are constrained by a priori assumptions. We compared a data
      driven novel application of principal component analysis (PCA) to conventional
      methods. We studied 122 fMRI data sets from control and localization-related
      epilepsy patients provided by five children's hospitals. Each subject performed
      an auditory description decision task. The data sets, acquired with different
      scanners but similar acquisition parameters, were processed through fMRIB
      software library to obtain 3D activation maps in standard space. A PCA analysis
      was applied to generate the decisional space and the data cluster into three
      distinct activation patterns. The classified activation maps were interpreted by
      (1) blinded reader rating based on predefined language patterns and (2) by
      language area ROI-based LI (i.e., fixed threshold vs. bootstrap approaches). The
      different classification results were compared through kappa inter-rater
      agreement statistics. The unique decisional space classified activation maps into
      three clusters (a) lower intensity typical language representation, (b) higher
      intensity typical, as well as (c) higher intensity atypical representation. Inter
      rater agreements among the three raters were excellent (Fleiss kappa = 0.85, P =
      0.05). There was substantial to excellent agreement between the conventional
      visual rating and LI methods (kappa = 0.69-0.82, P = 0.05). The PCA-based method
      yielded excellent agreement with conventional methods (kappa = 0.82, P = 0.05).
      The automated and data-driven PCA decisional space segregates language-related
      activation patterns in excellent agreement with current clinical rating and ROI
      based methods.

PMID- 22461301
TI  - Enzymatic processing of angiotensin peptides by human glomerular endothelial
      cells.
AB  - The intraglomerular renin-angiotensin system (RAS) is linked to the pathogenesis
      of progressive glomerular diseases. Glomerular podocytes and mesangial cells play
      distinct roles in the metabolism of angiotensin (ANG) peptides. However, our
      understanding of the RAS enzymatic capacity of glomerular endothelial cells
      (GEnCs) remains incomplete. We explored the mechanisms of endogenous cleavage of
      ANG substrates in cultured human GEnCs (hGEnCs) using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and isotope-labeled
      peptide quantification. Overall, hGEnCs metabolized ANG II at a significantly
      slower rate compared with podocytes, whereas the ANG I processing rate was
      comparable between glomerular cell types. ANG II was the most abundant fragment
      of ANG I, with lesser amount of ANG-(1-7) detected. Formation of ANG II from ANG
      I was largely abolished by an ANG-converting enzyme (ACE) inhibitor, whereas ANG
      (1-7) formation was decreased by a prolylendopeptidase (PEP) inhibitor, but not
      by a neprilysin inhibitor. Cleavage of ANG II resulted in partial conversion to
      ANG-(1-7), a process that was attenuated by an ACE2 inhibitor, as well as by an
      inhibitor of PEP and prolylcarboxypeptidase. Further fragmentation of ANG-(1-7)
      to ANG-(1-5) was mediated by ACE. In addition, evidence of aminopeptidase N
      activity (APN) was demonstrated by detecting amelioration of conversion of ANG
      III to ANG IV by an APN inhibitor. While we failed to find expression or activity
      of aminopeptidase A, a modest activity attributable to aspartyl aminopeptidase
      was detected. Messenger RNA and gene expression of the implicated enzymes were
      confirmed. These results indicate that hGEnCs possess prominent ACE activity, but
      modest ANG II-metabolizing activity compared with that of podocytes. PEP, ACE2,
      prolylcarboxypeptidase, APN, and aspartyl aminopeptidase are also enzymes
      contained in hGEnCs that participate in membrane-bound ANG peptide cleavage.
      Injury to specific cell types within the glomeruli may alter the intrarenal RAS
      balance.

PMID- 22461302
TI  - Protein abundance of urea transporters and aquaporin 2 change differently in
      nephrotic pair-fed vs. non-pair-fed rats.
AB  - Salt and water retention is a hallmark of nephrotic syndrome (NS). In this study,
      we test for changes in the abundance of urea transporters, aquaporin 2 (AQP2), Na
      K-2Cl cotransporter 2 (NKCC2), and Na-Cl cotransporter (NCC), in non-pair-fed and
      pair-fed nephrotic animals. Doxorubicin-injected male Sprague-Dawley rats (n =
      10) were followed in metabolism cages. Urinary excretion of protein, sodium, and
      urea was measured periodically. Kidney inner medulla (IM), outer medulla, and
      cortex tissue samples were dissected and analyzed for mRNA and protein
      abundances. At 3 wk, all doxorubicin-treated rats developed features of NS, with
      a ninefold increase in urine protein excretion (from 144 +/- 21 to 1,107 +/- 165
      mg/day; P < 0.001) and reduced urinary sodium excretion (from 0.17 to 0.12
      meq/day; P < 0.001). Urine osmolalities were reduced in the nephrotic animals
      (1,057 +/- 37, treatment vs. 1,754 +/- 131, control). Unlike animals fed ad
      libitum, UT-A1 protein abundance was unchanged in nephrotic pair-fed rats.
      Glycosylated AQP2 was reduced in the IM base of both nephrotic groups. Abundances
      of NKCC2 and NCC were consistently reduced (71 +/- 7 and 33 +/- 13%,
      respectively) in both nephrotic pair-fed animals and animals fed ad libitum. In
      pair-fed nephrotic rats, we observed an increase in the cleaved form of membrane
      bound gamma-epithelial sodium channel (ENaC). However, alpha- and beta-ENaC
      subunits were unaltered. NKCC2 and AQP2 mRNA levels were similar in treated vs.
      control rats. We conclude that dietary protein intake affects the response of
      medullary transport proteins to NS.

PMID- 22461303
TI  - Mechanisms of angiotensin II-enhanced connecting tubule glomerular feedback.
AB  - Increasing Na delivery to the connecting tubule (CNT) causes afferent arteriole
      (Af-Art) dilation, a process we call CNT glomerular feedback (CTGF). Angiotensin
      II (ANG II) in the CNT lumen enhances CTGF via PKC. We hypothesized that luminal
      ANG II stimulates CTGF via activation of protein kinase C (PKC), NADPH oxidase 2
      (NOX2), and enhanced production of superoxide (O(2)(-)). Rabbit Af-Arts and
      adherent CNTs were microdissected and microperfused in vitro. Dilation of the Af
      Art was induced by increasing luminal CNT NaCl from 0 to 5, 10, 30, 45, and 80
      mM, and the concentration of NaCl that elicited a half-maximal response (EC(50))
      was calculated. Compared with vehicle, adding ANG II (10(-9) M) to the CNT lumen
      reduced EC(50) from 37 +/- 3 to 14 +/- 1 mM (P < 0.001), indicating ANG II
      potentiates CTGF. In the presence of ANG II, the O(2)(-) scavenger tempol (10(-4)
      M) increased EC(50) from 20 +/- 4 to 41 +/- 3 mM (P < 0.01), the NOX inhibitor
      apocynin (10(-5) M) increased EC(50) from 17 +/- 2 to 39 +/- 4 mM (P < 0.01), and
      the specific NOX2 inhibitor gp91ds-tat (10(-5) M) increased EC(50) from 19 +/- 2
      to 34 +/- 2 mM (P < 0.01). However, tempol, apocynin, and gp91ds-tat had no
      effect on CTGF in the absence of ANG II. Compared with vehicle, the PKC activator
      PMA (2 * 10(-7) M) decreased EC(50) from 35 +/- 2 to 14 +/- 1 (P < 0.001). In the
      presence of PMA, tempol increased EC(50) from 14 +/- 2 to 35 +/- 2 mM (P < 0.01).
      We conclude the PKC/NOX2/O(2)(-) pathway mediates the enhancement of CTGF by
      luminal ANG II but it does not participate in CTGF in the absence of ANG II.

PMID- 22461306
TI  - Bioinspired underwater bonding and debonding on demand.

PMID- 22461305
TI  - Tumor necrosis factor-alpha receptor type 1, not type 2, mediates its acute
      responses in the kidney.
AB  - Acute administration of tumor necrosis factor-alpha (TNF-alpha) resulted in
      decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) but
      induced diuretic and natriuretic responses in mice. To define the receptor
      subtypes involved in these renal responses, experiments were conducted to assess
      the responses to human recombinant TNF-alpha (0.3 ng.min(-1).g body wt(-1) iv
      infusion for 75 min) in gene knockout (KO) mice for TNF-alpha receptor type 1
      (TNFalphaR1 KO, n = 5) or type 2 (TNFalphaR2 KO, n = 6), and the results were
      compared with those obtained in corresponding wild-type [WT (C57BL/6), n = 6]
      mice. Basal levels of RBF (PAH clearance) and GFR (inulin clearance) were similar
      in TNFalphaR1 KO, but were lower in TNFalphaR2 KO, than WT mice. TNF-alpha
      infusion in WT mice decreased RBF and GFR but caused a natriuretic response, as
      reported previously. In TNFalphaR1 KO mice, TNF-alpha infusion failed to cause
      such vasoconstrictor or natriuretic responses; rather, there was an increase in
      RBF and a decrease in renal vascular resistance. Similar responses were also
      observed with infusion of murine recombinant TNF-alpha in TNFalphaR1 KO mice (n =
      5). However, TNF-alpha infusion in TNFalphaR2 KO mice caused changes in renal
      parameters qualitatively similar to those observed in WT mice.
      Immunohistochemical analysis in kidney slices from WT mice demonstrated that
      while both receptor types were generally located in the renal vascular and
      tubular cells, only TNFalphaR1 was located in vascular smooth muscle cells. There
      was an increase in TNFalphaR1 immunoreactivity in TNFalphaR2 KO mice, and vice
      versa, compared with WT mice. Collectively, these functional and
      immunohistological findings in the present study demonstrate that the activation
      of TNFalphaR1, not TNFalphaR2, is mainly involved in mediating the acute renal
      vasoconstrictor and natriuretic actions of TNF-alpha.

PMID- 22461307
TI  - Amine-catalyzed [3+2] Huisgen cycloaddition strategy for the efficient assembly
      of highly substituted 1,2,3-triazoles.
AB  - An enamine-catalyzed strategy has been utilized to fully promote the Huisgen
      [3+2] cycloaddition with a broad spectrum of carbonyl compounds and azides,
      thereby permitting the efficient assembly of a vast pool of highly substituted
      1,2,3-triazoles. In particular, the employment of commonly used and commercially
      available carbonyl compounds has resulted in the introduction of a diverse set of
      functional groups, such as alkyl, aryl, nitrile, ester, and ketone groups, at the
      1-, 4-, or 5-positions of the 1,2,3-triazole scaffold. This approach might be
      manipulated to access more useful and sophisticated heterocyclic compounds. Most
      significantly, the reaction process exhibits complete regioselectivity, with the
      formation of only one regioisomer.

PMID- 22461304
TI  - SDF-1 activates papillary label-retaining cells during kidney repair from injury.
AB  - The adult kidney contains a population of low-cycling cells that resides in the
      papilla. These cells retain for long periods S-phase markers given as a short
      pulse early in life; i.e., they are label-retaining cells (LRC). In previous
      studies in adult rat and mice, we found that shortly after acute kidney injury
      many of the quiescent papillary LRC started proliferating (Oliver JA, Klinakis A,
      Cheema FH, Friedlander J, Sampogna RV, Martens TP, Liu C, Efstratiadis A, Al
      Awqati Q. J Am Soc Nephrol 20: 2315-2327, 2009; Oliver JA, Maarouf O, Cheema FH,
      Martens TP, Al-Awqati Q. J Clin Invest 114: 795-804, 2004) and, with cell
      tracking experiments, we found upward migration of some papillary cells including
      LRC (Oliver JA, Klinakis A, Cheema FH, Friedlander J, Sampogna RV, Martens TP,
      Liu C, Efstratiadis A, Al-Awqati Q. J Am Soc Nephrol 20: 2315-2327, 2009). To
      identify molecular cues involved in the activation (i.e., proliferation and/or
      migration) of the papillary LRC that follows injury, we isolated these cells from
      the H2B-GFP mice and found that they migrated and proliferated in response to the
      cytokine stromal cell-derived factor-1 (SDF-1). Moreover, in a papillary organ
      culture assay, the cell growth out of the upper papilla was dependent on the
      interaction of SDF-1 with its receptor Cxcr4. Interestingly, location of these
      two proteins in the kidney revealed a complementary location, with SDF-1 being
      preferentially expressed in the medulla and Cxcr4 more abundant in the papilla.
      Blockade of Cxcr4 in vivo prevented mobilization of papillary LRC after transient
      kidney ischemic injury and worsened its functional consequences. The data
      indicate that the SDF-1/Cxcr4 axis is a critical regulator of papillary LRC
      activation following transient kidney injury and during organ repair.

PMID- 22461308
TI  - Mutation update on the CHD7 gene involved in CHARGE syndrome.
AB  - CHD7 is a member of the chromodomain helicase DNA-binding (CHD) protein family
      that plays a role in transcription regulation by chromatin remodeling. Loss-of
      function mutations in CHD7 are known to cause CHARGE syndrome, an autosomal
      dominant malformation syndrome in which several organ systems, for example, the
      central nervous system, eye, ear, nose, and mediastinal organs, are variably
      involved. In this article, we review all the currently described CHD7 variants,
      including 183 new pathogenic mutations found by our laboratories. In total, we
      compiled 528 different pathogenic CHD7 alterations from 508 previously published
      patients with CHARGE syndrome and 294 unpublished patients analyzed by our
      laboratories. The mutations are equally distributed along the coding region of
      CHD7 and most are nonsense or frameshift mutations. Most mutations are unique,
      but we identified 94 recurrent mutations, predominantly arginine to stop codon
      mutations. We built a locus-specific database listing all the variants that is
      easily accessible at www.CHD7.org. In addition, we summarize the latest data on
      CHD7 expression studies, animal models, and functional studies, and we discuss
      the latest clinical insights into CHARGE syndrome.

PMID- 22461309
TI  - Emergence of NDM-1-producing Klebsiella pneumoniae in Guatemala.

PMID- 22461310
TI  - In HIV-infected patients, some differential alterations of CD4 and CD8 T cell
      homeostasis may not be restored by >= 7 years of highly active antiretroviral
      therapy, in spite of good CD4 T cell repopulation.

PMID- 22461311
TI  - Are susceptibility tests enough, or should laboratories still seek ESBLs and
      carbapenemases directly?
AB  - Recent EUCAST advice asserts that, with low breakpoints, susceptibility results
      for cephalosporins and carbapenems can be reported 'as found', even for strains
      with extended-spectrum beta-lactamases (ESBLs) and carbapenemases. The CLSI has
      similar advice, but with higher ceftazidime and cefepime breakpoints than those
      of EUCAST. Pharmacodynamic and animal data are used to support these views, along
      with some analysis of clinical case series. We contend that such advice is
      misguided on three counts. First, whilst there are cases on record where
      cephalosporins and carbapenems have proved effective against infections due to
      low-MIC ESBL producers and low-MIC carbapenemase producers, respectively, there
      are similar numbers of cases where such therapy has failed. Second, routine
      susceptibility testing is less precise than in research analyses, meaning that
      ESBL and carbapenemase producers with 'real' MICs of 1-8 mg/L will oscillate
      between susceptibility categories according to who tests them and how. Third,
      although EUCAST continues to advocate ESBL and carbapenemase detection for
      epidemiological purposes, the likely consequence of not seeking these enzymes for
      treatment purposes is that some laboratories will not seek them at all, leading
      to a loss of critical infection control information. In short, it is prudent to
      continue to seek ESBLs and carbapenemases directly and, where they are found,
      generally to avoid substrate drugs as therapy.

PMID- 22461312
TI  - Antimicrobial resistance among non-fermenting Gram-negative bacteria in Saudi
      Arabia.
AB  - OBJECTIVES: Non-fermentative Gram-negative bacilli (non-fermenters) can cause
      serious healthcare-associated infections and are often resistant to multiple
      antibiotics. We examined resistance rates among these bacteria from different
      regions of Saudi Arabia. METHODS: A cross-sectional study between January and
      December 2009 examined 8908 clinical non-fermenters from 24 hospitals across
      Saudi Arabia. Susceptibility testing was monitored to ensure compliance with CLSI
      guidelines, but the antibiotics tested were at the hospitals' discretion.
      RESULTS: Out of the 8908 non-fermenters, most were Pseudomonas aeruginosa
      (72.9%), followed by Acinetobacter baumannii (25.3%) and Stenotrophomonas
      maltophilia (1.8%). Resistance rates among P. aeruginosa were: polymyxin B, 2.2%;
      imipenem, 15.9%; ciprofloxacin, 22.0%; amikacin, 22.9%; and gentamicin, 31.2%.
      Resistance rates among A. baumannii were: imipenem, 5.4%; polymyxin B, 13.2%;
      ciprofloxacin, 64.0%; trimethoprim/sulfamethoxazole, 73.8%; amikacin, 76.9%; and
      gentamicin, 77.8%. Resistance rates among S. maltophilia were: polymyxin B, 6.9%;
      trimethoprim/sulfamethoxazole, 20.5%; and ciprofloxacin, 38.9%. There was major
      variation in resistance rates between geographical regions. CONCLUSIONS:
      Resistance rates among non-fermenters were high in Saudi Arabia and were variable
      among regions.

PMID- 22461314
TI  - Safety and effectiveness of a selective strategy for coronary artery
      revascularization before transcatheter aortic valve implantation.
AB  - OBJECTIVES: We assessed the safety and effectiveness of a selective percutaneous
      revascularization strategy before TAVI in a single-center prospective registry.
      BACKGROUND: Management of Coronary Artery Disease (CAD) before Transcatheter
      Aortic Valve Implantation (TAVI) is not yet established. METHODS: Percutaneous
      Coronary Intervention (PCI) was scheduled in proximal-to-mid coronary segment
      lesions on major coronary branches. TAVI was performed by percutaneous trans
      femoral, trans-subclavian or trans-apical approach, using either the self
      expandable III generation CoreValve (Medtronic, Minneapolis, Minnesota USA) or
      the Edwards SAPIEN(TM) /SAPIEN XT balloon-expandable prosthesis (Edwards
      Lifesciences Irvine, CA). Clinical and echocardiographic follow-up was collected
      at 30-day, 3,6,12-month and yearly thereafter. RESULTS: Out of 191 patients who
      underwent TAVI, 113 (59.2%) had CAD. Mean age was 80.5 +/- 6.9 years (57.6%
      female), logistic EuroSCORE was 21.4% +/- 13.4. Twenty-seven (14.1%) patients had
      previous percutaneous and 29 (15.2%) surgical revascularization. PCI was
      performed as scheduled before TAVI in 39 (20.4%) patients, without adverse
      events. Complete anatomical revascularization was obtained in 38 of 113 CAD
      patients (33.6%). After TAVI, 30-day mortality was 4.2%, and was comparable
      between CAD and no-CAD patients (P = ns), while 30-day myocardial infarction
      incidence was 2.6% and occurred only in the CAD group (4.4%, P = 0.06). Overall
      mortality at follow-up (12.9 +/- 9.5 months) was 14.8%, without difference
      between groups (P = 0.88). At follow-up, five patients underwent coronary
      revascularization. CONCLUSIONS: In this study, the incidence of CAD is high in
      patients referred for TAVI. A selective, clinical based, coronary
      revascularization before TAVI seemed to be safe, and was associated with an
      outcome similar to those observed in no-CAD TAVI patients.

PMID- 22461313
TI  - Cortical connections of auditory cortex in marmoset monkeys: lateral belt and
      parabelt regions.
AB  - The current working model of primate auditory cortex is constructed from a number
      of studies of both new and old world monkeys. It includes three levels of
      processing. A primary level, the core region, is surrounded both medially and
      laterally by a secondary belt region. A third level of processing, the parabelt
      region, is located lateral to the belt. The marmoset monkey (Callithrix jacchus
      jacchus) has become an important model system to study auditory processing, but
      its anatomical organization has not been fully established. In previous studies,
      we focused on the architecture and connections of the core and medial belt areas
      (de la Mothe et al., 2006a, J Comp Neurol 496:27-71; de la Mothe et al., 2006b, J
      Comp Neurol 496:72-96). In this study, the corticocortical connections of the
      lateral belt and parabelt were examined in the marmoset. Tracers were injected
      into both rostral and caudal portions of the lateral belt and parabelt. Both
      regions revealed topographic connections along the rostrocaudal axis, where
      caudal areas of injection had stronger connections with caudal areas, and rostral
      areas of injection with rostral areas. The lateral belt had strong connections
      with the core, belt, and parabelt, whereas the parabelt had strong connections
      with the belt but not the core. Label in the core from injections in the parabelt
      was significantly reduced or absent, consistent with the idea that the parabelt
      relies mainly on the belt for its cortical input. In addition, the present and
      previous studies indicate hierarchical principles of anatomical organization in
      the marmoset that are consistent with those observed in other primates.

PMID- 22461315
TI  - Brain plasticity in the motor network is correlated with disease progression in
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To test the influence of functional cerebral reorganization in
      amyotrophic lateral sclerosis (ALS) on disease progression. METHODS: Nineteen
      predominantly right-handed ALS patients and 21 controls underwent clinical
      evaluation, functional Magnetic Resonance Imaging (fMRI), and diffusion tensor
      imaging. Patients were clinically re-evaluated 1 year later and followed until
      death. For fMRI, subjects executed and imagined a simple hand-motor task. Between
      group comparisons were performed, and correlations were searched with motor
      deficit arm Medical Research Council (MRC) score, disease progression ALS
      Functional Rating Scale (ALSFRS), and survival time. RESULTS: By the MRC score,
      the hand strength was lowered by 12% in the ALS group predominating on the right
      side in accordance with an abnormal fractional anisotropy (FA) limited to the
      left corticospinal tract (37.3% reduction vs. controls P < 0.01). Compared to
      controls, patients displayed overactivations in the controlateral parietal (P <
      0.004) and somatosensory (P < 0.004) cortex and in the ipsilateral parietal (P <
      0.01) and somatosensory (P < 0.01) cortex to right-hand movement. Movement
      imagination gave similar results while no difference occurred with left-hand
      tasks. Stepwise regression analysis corrected for multiple comparisons showed
      that controlateral parietal activity was inversely correlated with disease
      progression (R(2) = 0.43, P = 0.001) and ipsilateral somatosensory activations
      with the severity of the right-arm deficit (R(2) = 0.48, P = 0.001). CONCLUSIONS:
      Cortical Blood Oxygen Level Dependent (BOLD) signal changes occur in the brain of
      ALS patients during a simple hand-motor task when the motor deficit is still
      moderate. It is correlated with the rate of disease progression suggesting that
      brain functional rearrangement in ALS may have prognostic implications.

PMID- 22461317
TI  - Activation of molecular oxygen by anionic gold clusters.

PMID- 22461316
TI  - Sonographic predictors of surgery in fetal coarctation of the aorta.
AB  - OBJECTIVES: Isolated fetal coarctation of the aorta (CoA) has high false-positive
      diagnostic rates by cardiologists in tertiary centers. Isthmal diameter Z-scores
      (I), ratio of isthmus to duct diameters (I:D), and visualization of CoA shelf
      (Shelf) and isthmal flow disturbance (Flow) distinguish hypoplastic from normal
      aortic arches in retrospective studies, but their ability to predict a need for
      perinatal surgery is unknown. The aim of this study was to determine whether
      these four sonographic features could differentiate prenatally cases which would
      require neonatal surgery in a prospective cohort diagnosed with CoA by a
      cardiologist. METHODS: From 83 referrals with cardiac disproportion (January 2006
      to August 2010), we identified 37 consecutive fetuses diagnosed with CoA.
      Measurements of I and I:D were made and the presence of Shelf or Flow recorded.
      Sensitivity, specificity and areas under receiver-operating characteristics
      curves, using previously reported limits of I < - 2 and I:D < 0.74, as well as
      Shelf and Flow were compared at first and final scan. Associations between
      surgery and predictors were compared using multivariable logistic regression and
      changes in measurements using ANCOVA. RESULTS: Among the 37 fetuses, 30 (81.1%)
      required surgery and two with an initial diagnosis of CoA were revised to normal
      following isthmal growth, giving an 86% diagnostic accuracy at term. The median
      age at first scan was 22.4 (range. 16.6-7.0) weeks and the median number of scans
      per fetus was three (range, one to five). I < - 2 at final scan was the most
      powerful predictor (odds ratio, 3.6 (95% CI, 0.47-27.3)). Shelf was identified in
      66% and Flow in 50% of fetuses with CoA. CONCLUSION: Incorporation of these four
      sonographic parameters in the assessment of fetuses with suspected CoA at a
      tertiary center resulted in better diagnostic precision regarding which cases
      would require neonatal surgery than has been reported previously.

PMID- 22461318
TI  - SAMHD1 is a nucleic-acid binding protein that is mislocalized due to aicardi
      goutieres syndrome-associated mutations.
AB  - Aicardi-Goutieres syndrome (AGS) is a rare inherited autoimmune disease caused by
      mutations in genes encoding the RNase H2 subunits A, B, and C; the DNase three
      prime repair exonuclease 1 (TREX1); and sterile alpha motif (SAM) domain and HD
      domain-containing protein 1 (SAMHD1). Using unbiased affinity purification
      coupled to protein mass spectrometry, we identify SAMHD1 as a nucleic-acid
      binding protein displaying a preference for RNA over DNA. In contrast to TREX1
      and the RNase H2 complex, SAMHD1 has no obvious nuclease activity. In addition,
      interrogating truncation mutants of SAMHD1 observed in AGS patients, we map the
      nucleic-acid-binding domain to residues 164-442, thus overlapping with the HD
      domain. Furthermore, we show that although wild-type SAMHD1 displays almost
      exclusive nuclear localization, 11 of 12 SAMHD1 mutants show at least partial
      mislocalization to the cytosol. Overall, these data suggest that SAMHD1 has a
      role in the nucleus that, if disrupted by mutation, leads to cytosolic
      accumulation of SAMHD1 and autoimmune disease.

PMID- 22461319
TI  - Biomolecule-directed assembly of self-supported, nanoporous, conductive, and
      luminescent single-walled carbon nanotube scaffolds.
AB  - A single-walled carbon nanotube self-suspended network of exceptionally low
      density is formed by DNA-streptavidin-assisted assembly where the DNA complex
      serves as a cross-shaped point connector. The macroscopic nanotube aerogel is
      conductive and luminescent and presents an excellent scaffold for subsequent
      functionalization. For example, platinum and titanium dioxide coating of the
      nanotube network is demonstrated.

PMID- 22461320
TI  - Nucleophilicity parameters of enamides and their implications for organocatalytic
      transformations.
AB  - The kinetics of the reactions of eleven substituted enamides with benzhydrylium
      ions (diarylcarbenium ions) were determined in acetonitrile solution. The second
      order rate constants follow the correlation log k(2) (20  degrees C)=s(N)(E+N),
      which allowed us to derive reactivity parameters N and s(N). With 4.6<N<7.1,
      enamides had similar nucleophilicities to enol ethers and non- or weakly
      activated indoles and pyrroles. The combination of the N and s(N) parameters with
      the previously reported E parameters of typical Michael acceptors, alpha,beta
      unsaturated iminium ions, and the chlorinating agent hexachlorocyclohexa-2,4
      dienone allowed us to reliably reproduce the experimental rate constants of the
      reactions with these electrophiles. The reactions of enamides with alpha,beta
      unsaturated iminium ions only proceeded in the presence of bases (e.g., 2,6
      lutidine), which was explained by the low Lewis acidities of the iminium ions.
      The consequences of these results for the use of enamides in organocatalytic
      reactions are discussed.

PMID- 22461321
TI  - Chemiluminescence detection of cannabinoids and related compounds with acidic
      potassium permanganate.
AB  - This is the first report of chemiluminescence from the reaction of cannabinoids
      with acidic potassium permanganate, which we have applied to the high performance
      liquid chromatography (HPLC) determination of cannabidiol (CBD) in industrial
      grade hemp. The intensities of the light-producing reactions with two
      commercially available cannabinoid standards were compared to that of seven model
      phenolic analytes. Resorcinol, representing the parent phenolic moiety of the
      cannabinoid class, was shown to react with the permanganate reagents in a manner
      more similar to phenol than to its hydroxyphenol positional isomers, pyrocatechol
      and hydroquinone. Alkyl substituents on the phenolic ring, however, have a
      considerable impact on emission intensity that is dependent upon the position of
      the groups and the composition of the permanganate reagent. This analytical
      approach has potential for the determination of other cannabinoids including
      Delta(9) -tetrahydrocannabinol in drug-grade cannabis.

PMID- 22461322
TI  - Descending aorta thrombus in a neonate mimicking coarctation of the aorta:
      mechanical thrombectomy using the AngioJet((r)) catheter.
AB  - A 5-day-old neonate presented in shock, with signs and symptoms of severe
      coarctation of the aorta. He was diagnosed with a patent aortic arch, and a
      completely thrombosed abdominal aorta. The authors report the successful
      transcatheter removal of the entire thrombus using the AngioJet((r)) Thrombectomy
      system. This represents the first published use of the AngioJet((r)) catheter in
      the aorta of a pediatric patient.

PMID- 22461323
TI  - (Still) longing for food: insulin reactivity modulates response to food pictures.
AB  - Overweight and obesity pose serious challenges to public health and are promoted
      by our food-rich environment. We used functional magnetic resonance imaging
      (fMRI) to investigate reactivity to food cues after overnight fasting and
      following a standardized caloric intake (i.e., a 75 g oral glucose tolerance
      test, OGTT) in 26 participants (body mass index, BMI between 18.5 and 24.9 kg m(
      2)). They viewed pictures of palatable food and low-level control stimuli in a
      block design and rated their current appetite after each block. Compared to
      control pictures, food pictures activated a large bilateral network typically
      involved in homeostatically and hedonically motivated food processing. Glucose
      ingestion was followed by decreased activation in the basal ganglia and
      paralimbic regions and increased activation in parietal and occipital regions.
      Plasma level increases in insulin correlated with cue-induced appetite at the
      neural and behavioral level. High insulin increases were associated with reduced
      activation in various bilateral regions including the fusiform gyrus, the
      superior temporal gyrus, the medial frontal gyrus, and the limbic system in the
      right hemisphere. In addition, they were accompanied by lower subjective appetite
      ratings following food pictures and modulated the neural response associated with
      it (e.g., in the fusiform gyrus). We conclude that individual insulin reactivity
      is critical to reduce food-cue responsivity after an initial energy intake and
      thereby may help to counteract overeating.

PMID- 22461324
TI  - Virtual bronchoscopy for evaluating cervical tumors of the fetus.
AB  - We report on four cases of fetal cervical tumor, comprising three lymphangiomas
      and one teratoma, evaluated by ultrasound and magnetic resonance imaging (MRI)
      between 26 and 37 weeks' gestation. The aim was to investigate the use of virtual
      bronchoscopy to evaluate fetal airway patency in each case. A three-dimensional
      (3D) model of the airway was created from overlapping image layers generated by
      MRI. The files obtained were manipulated using 3D modeling software, allowing the
      virtual positioning of observation cameras, adjustment of lighting parameters and
      creation of simulated 3D movies for analysis of a virtual path through the model.
      In all fetuses, fetal airway patency was clearly demonstrated by virtual
      bronchoscopy and this was confirmed postnatally. MRI with virtual bronchoscopy
      could become a useful tool for studying fetal airway patency in cases of cervical
      tumor.

PMID- 22461325
TI  - In silico inspired total synthesis of (-)-dolabriferol.

PMID- 22461326
TI  - Inherited deleterious variants in GALNT12 are associated with CRC susceptibility.
AB  - A recent report detailed the occurrence of both somatic and constitutional
      variants in the GALNT12 gene, located at 9q22.33, in some colorectal cancer (CRC)
      patients. In this study, we investigate the occurrence of inherited deleterious
      variants in GALNT12 in 118 families referred to a cancer genetics clinic. We
      discovered two deleterious variants (c.907G>A (p.Asp303Asn); c.1187A>G
      (p.Tyr396Cys)) in 4/118 probands. The variants, which were not found in 149
      control individuals (P = 0.0376), cosegregate with CRC and/or adenomatous polyps
      in other family members. The probability by chance that cosegregation of c.907G>A
      with CRC and/or adenomatous polyps occurred, in the two pedigrees combined, was
      1.56%. Although this study does not provide irrefutable evidence that GALNT12
      variants are highly penetrant alleles that predispose to CRC in the majority of
      unexplained hereditary CRC families, it does provide additional evidence to
      support an important role of these variants in a proportion of this considerable
      high-risk group.

PMID- 22461327
TI  - Biocompatible triplex Ag@SiO2@mTiO2 core-shell nanoparticles for simultaneous
      fluorescence-SERS bimodal imaging and drug delivery.
AB  - Herein, we report the synthesis of biocompatible triplex Ag@SiO(2)@mTiO(2) core
      shell nanoparticles (NPs) for simultaneous fluorescence-surface-enhanced Raman
      scattering (F-SERS) bimodal imaging and drug delivery. Stable Raman signals were
      created by typical SERS tags that were composed of Ag NPs for optical
      enhancement, a reporter molecule of 4-mercaptopyridine (4-Mpy) for a
      spectroscopic signature, and a silica shell for protection. A further coating of
      mesoporous titania (mTiO(2)) on the SERS tags offered high loading capacity for a
      fluorescence dye (flavin mononucleotide) and an anti-cancer drug (doxorubicin
      (DOX)), thereby endowing the material with fluorescence-imaging and therapeutic
      functions. The as-prepared F-SERS dots exhibited strong fluorescence when excited
      by light at 460 nm whilst a stable, characteristic 4-Mpy SERS signal was detected
      when the excitation wavelength was changed to longer wavelength (632.8 nm), both
      in solution and after incorporation inside living cells. Their excellent
      biocompatibility was demonstrated by low cytotoxicity against MCF-7 cells, even
      at a high concentration of 100 MUg  mL(-1). In vitro cell cytotoxicity confirmed
      that DOX-loaded F-SERS dots had a comparable or even greater therapeutic effect
      compared with the free drug, owing to the increased cell-uptake, which was
      attributed to the possible endocytosis mechanism of the NPs. To the best of our
      knowledge, this is the first proof-of-concept investigation on a multifunctional
      nanomedicine that possessed a combined capacity for fast and multiplexed F-SERS
      labeling as well as drug-loading for cancer therapy.

PMID- 22461328
TI  - Patterning hierarchy in direct and inverse opal crystals.
AB  - Biological strategies for bottom-up synthesis of inorganic crystalline and
      amorphous materials within topographic templates have recently become an
      attractive approach for fabricating complex synthetic structures. Inspired by
      these strategies, herein the synthesis of multi-layered, hierarchical inverse
      colloidal crystal films formed directly on topographically patterned substrates
      via evaporative deposition, or "co-assembly", of polymeric spheres with a
      silicate sol-gel precursor solution and subsequent removal of the colloidal
      template, is described. The response of this growing composite colloid-silica
      system to artificially imposed 3D spatial constraints of various geometries is
      systematically studied, and compared with that of direct colloidal crystal
      assembly on the same template. Substrates designed with arrays of rectangular,
      triangular, and hexagonal prisms and cylinders are shown to control
      crystallographic domain nucleation and orientation of the direct and inverse
      opals. With this bottom-up topographical approach, it is demonstrated that the
      system can be manipulated to either form large patterned single crystals, or
      crystals with a fine-tuned extent of disorder, and to nucleate distinct colloidal
      domains of a defined size, location, and orientation in a wide range of length
      scales. The resulting ordered, quasi-ordered, and disordered colloidal crystal
      films show distinct optical properties. Therefore, this method provides a means
      of controlling bottom-up synthesis of complex, hierarchical direct and inverse
      opal structures designed for altering optical properties and increased
      functionality.

PMID- 22461329
TI  - Balloon angioplasty of recoarctation of the neoaortic arch after the Norwood
      operation: factors affecting outcome and recurrence.
AB  - BACKGROUND: Balloon angioplasty (BA) is effective in relieving neoaorta
      recoarctation (reCoa) after the Norwood procedure. However, recurrence is not
      uncommon and risk factors for success and recurrence require further elucidation.
      We report the results of BA for reCoa following the Norwood procedure. We examine
      acute results and risk factors associated with success and recurrence after BA.
      METHODS: Patients who underwent BA between November 2000 and June 2010 were
      studied. Factors for immediate success and recurrence after BA were determined
      using logistic regression. Recurrence-free survival was evaluated using the
      Kaplan-Meier curve. RESULTS: Forty-seven angioplasties were performed in 39
      patients. Mean age at catheterization was 5.0 +/- 4.1 months. BA was successful
      in 40 angioplasties (85.1%). A higher preprocedure gradient across the
      coarctation (P = 0.04) and a higher ratio of balloon to descending aorta (P =
      0.01) were associated with success. Six patients required redilation. Risk
      factors for recurrence included older age at Norwood (P = 0.02), younger age (P =
      0.03), lower weight (P = 0.04) and smaller body surface area at balloon
      angioplasty (BA) (P = 0.04), and shorter duration between surgery and angioplasty
      (P = 0.03). Freedom from recurrence from the first catheterization was 82% after
      6 months and 78% after 1 year. There were no neurologic sequelae or deaths.
      CONCLUSIONS: BA is effective acutely and long term with limited morbidity and
      mortality. Recurrence occurs usually within the first year. Delay in performing
      the initial angioplasty may be beneficial in reducing the risk of recurrence, but
      further study is needed.

PMID- 22461330
TI  - Depression and antidepressant use after stroke and transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Patients with stroke and transient ischemic attack (TIA)
      often have comparable comorbidities, but it is unclear whether they have similar
      rates of depression or antidepressant use. METHODS: This study was a secondary
      analysis of a prospective cohort registry that enrolled subjects from 2006 to
      2008 in the United States. Depression (defined by the Patient Health
      Questionnaire-8 score >= 10) and medication use were prospectively assessed 3 and
      12 months after hospitalization in 1450 subjects with ischemic stroke and 397
      subjects with TIA. RESULTS: The proportional frequency of depression after stroke
      and TIA was similar at 3 months (17.9% versus 14.3%, P=0.09) and at 12 months
      (16.4% versus 12.8%, P=0.08). The rates of newly identified depression between 3
      and 12 months were also similar (8.7% versus 6.2%, P=0.12). Persistent depression
      (defined as Patient Health Questionnaire-8 score >= 10 at both 3 and 12 months)
      was present in 134 (9.2%) of those with stroke and in 30 (7.6%) of those with
      TIA. Younger age, greater stroke-related disability, and inability to work at 3
      months were associated with persistent depression in subjects with stroke. Among
      subjects with persistent depression, 67.9% of those with stroke and 70.0% of
      those with TIA were not using antidepressants at either time point (P=0.920).
      CONCLUSIONS: Stroke and TIA subjects had a similar frequency of depression at 3
      and 12 months after hospitalization and similar rates of newly identified
      depression between 3 and 12 months. A high proportion of those with persistent
      depression was untreated.

PMID- 22461331
TI  - Preconditioning the brain: moving on to the next frontier of neurotherapeutics.

PMID- 22461333
TI  - Letter by Van de Werf et al regarding article, "using dabigatran in patients with
      stroke: a practical guide for clinicians".

PMID- 22461332
TI  - Pharmacological induction of heme oxygenase-1 by a triterpenoid protects neurons
      against ischemic injury.
AB  - BACKGROUND AND PURPOSE: Heme oxygenase-1 (HO-1) is an inducible Phase 2 enzyme
      that degrades toxic heme; its role in cerebral ischemia is not fully understood.
      We hypothesize that chemically induced HO-1 upregulation with the novel
      triterpenoid CDDO-Im (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a
      robust inducer of Phase 2 genes, protects neurons against ischemic injury.
      METHODS: Using 3 different models of ischemia, including oxygen-glucose
      deprivation in neuronal cultures, global ischemia in rats, and focal ischemia in
      mice, we determined (1) whether CDDO-Im induces HO-1 expression and protects
      against ischemic injury; and (2) whether HO-1 inhibition disrupts the
      neuroprotective effect of CDDO-Im. RESULTS: CDDO-Im treatment (50-300 nmol/L)
      resulted in 8-fold HO-1 upregulation in cultured neurons and protected against
      oxygen-glucose deprivation. The protection was abolished when the cultures were
      transfected with nuclear factor (erythroid-derived 2) like-2-shRNA or coincubated
      with tin protoporphyrin IX, a specific HO-1 inhibitor. In the rat model of global
      ischemia, intracerebroventricular infusion of CDDO-Im (0.5-1.5 MUg) augmented HO
      1 expression in hippocampal neurons and resulted in significant increases in CA1
      neuronal survival after global ischemia. To further strengthen the clinical
      relevance of the CDDO-Im treatment, we tested its effects in the mouse model of
      temporary focal ischemia (60 minutes). Postischemic intraperitoneal injection of
      CDDO-Im (10-100 MUg) enhanced HO-1 expression and significantly reduced
      neurological dysfunction and infarct volume. Intracerebroventricular infusion of
      tin protoporphyrin IX reduced the neuroprotective effect of CDDO-Im against
      global and focal ischemia. CONCLUSIONS: CDDO-Im confers neuroprotection against
      ischemic injury by upregulating HO-1, suggesting that enhance of HO-1 expression
      may be a legitimate strategy for therapeutic intervention of stroke.

PMID- 22461334
TI  - Letter by Casado-Naranjo et al regarding article, "using dabigatran in patients
      with stroke: a practical guide for clinicians".

PMID- 22461335
TI  - Letter by Freeman et al regarding article, "using dabigatran in patients with
      stroke: a practical guide for clinicians".

PMID- 22461336
TI  - Comparison of 2 extended activities of daily living scales with the Barthel Index
      and predictors of their outcomes: cohort study within the South London Stroke
      Register (SLSR).
AB  - BACKGROUND AND PURPOSE: Basic activities of daily living measures are often
      supplemented by extended activities of daily living. We compared the Frenchay
      Activities Index (FAI) and Nottingham Extended Activities of Daily Living (NEADL)
      with the Barthel Index (BI) in terms of distribution of scores, concurrent
      validity, reliability, and their agreement and investigated the predictors of
      scales outcomes. METHODS: Two hundred thirty-eight patients from the population
      based South London Stroke Register were assessed with the BI, FAI, and NEADL 3
      months after a first-ever stroke. The pairwise relationship was studied using
      correlations, fractional polynomial regression, and Bland and Altman plot; the
      baseline predictors, for example, sociodemography, case severity: National
      Institutes of Health Stroke Scale, and 7-day Abbreviated Memory Test,
      comorbidities, and acute treatments by negative binomial regression. RESULTS: The
      BI was highly affected by a ceiling effect (33% had the highest score), FAI was
      only affected by floor effect (19%), but NEADL was symmetrical with only 4%
      highest and lowest score. Despite high concurrent validity of the scales (r
      >=0.80, P<0.001), they agreed poorly only for the highest and the lowest level of
      activities. The association and agreement of NEADL with BI was higher than that
      of FAI with BI. Severe stroke patients (National Institutes of Health Stroke
      Scale >13) had 28% lower BI (79% lower FAI and 62% lower NEADL) score than
      nonsevere patients (P<=0.001). Cognitively intact patients (Abbreviated Memory
      Test: 8-10) had 2.3 times greater FAI values (65% higher NEADL) compared with
      impaired patients (P<0.001). CONCLUSIONS: The NEADL scale was symmetrical,
      concurrently valid with no floor and ceiling effects. It corresponded better with
      BI than FAI did confirming its basic activities of daily living properties, yet
      it is a more sensitive tool for extended activities of daily living without the
      floor and ceiling effects. Future functional status could be predicted by the
      acute stage National Institutes of Health Stroke Scale score, whereas only
      extended activities of daily living status could be predicted by the Abbreviated
      Memory Test score. Predicting future functional status at the acute stage may
      decrease unnecessary length of stay in acute care settings.

PMID- 22461337
TI  - The cortical control of cycling exercise in stroke patients: an fNIRS study.
AB  - Stroke survivors suffering from deficits in motor control typically have limited
      functional abilities, which could result in poor quality of life. Cycling
      exercise is a common training paradigm for restoring locomotion rhythm in
      patients. The provision of speed feedback has been used to facilitate the
      learning of controlled cycling performance and the neuromuscular control of the
      affected leg. However, the central mechanism for motor relearning of active and
      passive pedaling motions in stroke patients has not been investigated as
      extensively. The aim of this study was to measure the cortical activation
      patterns during active cycling with and without speed feedback and during power
      assisted (passive) cycling in stroke patients. A frequency-domain near-infrared
      spectroscopy (FD-NIRS) system was used to detect the hemodynamic changes
      resulting from neuronal activity during the pedaling exercise from the bilateral
      sensorimotor cortices (SMCs), supplementary motor areas (SMAs), and premotor
      cortices (PMCs). The variation in cycling speed and the level of symmetry of
      muscle activation of bilateral rectus femoris were used to evaluate cycling
      performance. The results showed that passive cycling had a similar cortical
      activation pattern to that observed during active cycling without feedback but
      with a smaller intensity of the SMC of the unaffected hemisphere. Enhanced PMC
      activation of the unaffected side with improved cycling performance was observed
      during active cycling with feedback, with respect to that observed without
      feedback. This suggests that the speed feedback enhanced the PMC activation and
      improved cycling performance in stroke patients.

PMID- 22461339
TI  - Crystal structures of the hydration states of Pigment Red 57:1.

PMID- 22461338
TI  - Detection of intracavitary uterine pathology using offline analysis of three
      dimensional ultrasound volumes: interobserver agreement and diagnostic accuracy.
AB  - OBJECTIVE: To estimate the diagnostic accuracy and interobserver agreement in
      predicting intracavitary uterine pathology at offline analysis of three
      dimensional (3D) ultrasound volumes of the uterus. METHODS: 3D volumes
      (unenhanced ultrasound and gel infusion sonography with and without power
      Doppler, i.e. four volumes per patient) of 75 women presenting with abnormal
      uterine bleeding at a 'bleeding clinic' were assessed offline by six examiners.
      The sonologists were asked to provide a tentative diagnosis. A histological
      diagnosis was obtained by hysteroscopy with biopsy or operative hysteroscopy.
      Proliferative, secretory or atrophic endometrium was classified as 'normal'
      histology; endometrial polyps, intracavitary myomas, endometrial hyperplasia and
      endometrial cancer were classified as 'abnormal' histology. The diagnostic
      accuracy of the six sonologists with regard to normal/abnormal histology and
      interobserver agreement were estimated. RESULTS: Intracavitary pathology was
      diagnosed at histology in 39% of patients. Agreement between the ultrasound
      diagnosis and the histological diagnosis (normal vs abnormal) ranged from 67 to
      83% for the six sonologists. In 45% of cases all six examiners agreed with regard
      to the presence/absence of intracavitary pathology. The percentage agreement
      between any two examiners ranged from 65 to 91% (Cohen's kappa, 0.31-0.81). The
      Schouten kappa for all six examiners was 0.51 (95% CI, 0.40-0.62), while the
      highest Schouten kappa for any three examiners was 0.69. CONCLUSION: When
      analyzing stored 3D ultrasound volumes, agreement between sonologists with regard
      to classifying the endometrium/uterine cavity as normal or abnormal as well as
      the diagnostic accuracy varied substantially. Possible actions to improve
      interobserver agreement and diagnostic accuracy include optimization of image
      quality and the use of a consistent technique for analyzing the 3D volumes.

PMID- 22461341
TI  - Trends in patient information preferences and acquisition.
AB  - BACKGROUND: Americans have access to medical information from a variety of
      sources, including readily accessible information on the Internet. As the
      American population's trust in online sources changes over time, it is possible
      that their cancer information-seeking preferences and behaviors also may change.
      OBJECTIVES: The purpose of this study is to assess longitudinal trends in cancer
      information-seeking preferences and behaviors based on data collected in 3 Health
      Information National Trends Surveys (HINTS) administered by the National Cancer
      Institute. METHODS: This is a retrospective secondary data analysis that compares
      the survey results of HINTS administered in 2003, 2005, and 2007. Frequency
      distribution, percentages, and variability were investigated, and findings were
      presented by age group, type of information source, and self-reported level of
      trust in medical information obtained. RESULTS: The analysis demonstrates trends
      in patient cancer information-seeking preferences and behaviors between 2003 and
      2007. With each survey, for example, the library gained increasing popularity as
      a source for cancer information. In 2007, survey participants viewed the library
      as their primary reference, followed by the Internet. On the other hand, views of
      health care providers as a primary information source decreased from 2003 to
      2007. CONCLUSION: Older generations appear to rely on Internet sources more often
      than they rely on health care providers for cancer information. Thus, it is
      important to ensure this patient group and all patients are accessing reliable
      resources when they seek cancer information, regardless of the source.

PMID- 22461342
TI  - Determining college performance of allied health students.
AB  - BACKGROUND: The need to find methods to reduce attrition rates in allied health
      programs has caught the attention of legislators and administrators of higher
      education institutions. METHODS: A quantitative method design was used to
      investigate academic achievement in college as a function of high school
      achievement, high school performance, aptitude, and proactive measures taken by
      students. College transcripts and a survey were used to collect data. Eighty-six
      participants volunteered for the study. The data were analyzed with multiple
      linear regressions. RESULTS: Academic achievement was found to be a function of
      the independent variables examined. Together, the variables accounted for 37% of
      the total variance in academic achievement among the respondents, as measured by
      college grade point average. The findings suggest that dual enrollment programs
      play an integral part in academic achievement and may help facilitate the
      transition of high school students into the radiologic sciences. The findings may
      assist educators working with students in public schools and in higher education,
      especially students seeking to enter the radiologic sciences as a profession.
      CONCLUSION: Dual enrollment programs may be 1 avenue to help reduce attrition
      rates in allied health programs, especially in radiologic technology programs.

PMID- 22461343
TI  - Florida mammographer disability training vs needs.
AB  - BACKGROUND: There is currently no minimum required competency for mammographers
      regarding imaging patients with physical disabilities. Yet, as disability
      prevalence rates increase, mammographers interact with more women with
      disabilities at breast imaging facilities. PURPOSE: To better understand the
      disability training that mammographers receive and desire, and the advice they
      would extend to colleagues regarding improving the experience when performing
      mammography on women with disabilities. METHODS: Within the context of a
      community and academic partnership, in-depth telephone interviews were conducted
      with 14 mammographers practicing in north central Florida. Grounded theory
      techniques facilitated analysis for major themes. RESULTS: The extent, content,
      and delivery of disability training varied among participants. Analysis revealed
      respondents' personal desires for training focused on positioning to "get the
      best breast image," while mammographers' advice to colleagues focused on the need
      to afford patience and respect to the patient. Four identified themes included
      learning on the job, asking for help, desired training to acquire the best
      possible image, and advice to other mammographers regarding patience. CONCLUSION:
      Mammographers value the disability training they receive as a foundation for
      continued learning on the job. Training should comprise both technical and social
      aspects of performing mammography on women with disabilities, including
      positioning, disability etiquette, and disability advocacy.

PMID- 22461344
TI  - Sinus pericranii.
AB  - Sinus pericranii is a rare anomaly that occurs when there is communication
      between the intracranial and extracranial venous systems. Accurate diagnosis is
      complicated because several other cranial masses can mimic sinus pericranii.
      Clinical, laboratory, and imaging assessments are all essential for identifying
      the anomaly. This article examines the comparative advantages of various
      diagnostic imaging modalities, current imaging techniques, and typical findings
      associated with sinus pericranii. Treatment and management options also are
      discussed.

PMID- 22461345
TI  - Solid organ donation and transplantation.
AB  - Medical imaging plays a key role in solid organ donation and transplantation. In
      addition to confirming the clinical diagnosis of brain death, imaging
      examinations are used to assess potential organ donors and recipients, evaluate
      donated organs, and monitor transplantation outcomes. This article introduces the
      history, biology, ethics, and institutions of organ donation and transplantation
      medicine. The article also discusses current and emerging imaging applications in
      the transplantation field and the controversial role of neuroimaging to confirm
      clinically diagnosed brain death.

PMID- 22461340
TI  - 11q13 is a susceptibility locus for hormone receptor positive breast cancer.
AB  - A recent two-stage genome-wide association study (GWAS) identified five novel
      breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more
      reliable estimates of the relative risk associated with these loci and
      investigate possible heterogeneity by subtype of breast cancer, we genotyped the
      variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies
      from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and
      48,772 controls of predominantly European ancestry. Four of the variants showed
      clear evidence of association (P <= 3 * 10(-9) ) and weak evidence was observed
      for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367,
      located on 11q13 (per-allele odds ratio 1.21, P = 4 * 10(-39) ). The association
      for rs614367 was specific to estrogen receptor (ER)-positive disease and
      strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas
      the associations for the other three loci did not differ by tumor subtype.

PMID- 22461346
TI  - Detecting a Salter-Harris fracture.

PMID- 22461347
TI  - Interpreting the waves.

PMID- 22461349
TI  - Breast care imaging: ghost of past?

PMID- 22461350
TI  - Mentoring within clinical education.

PMID- 22461352
TI  - Patient page. Magnetic resonance imaging.

PMID- 22461351
TI  - Developing and narrowing a topic.

PMID- 22461353
TI  - Appropriate use of breast imaging modalities.
AB  - Technological advancements in breast imaging continue to improve the ability to
      diagnose breast cancer early, particularly in women with dense breast tissue.
      Modalities other than mammography characterize areas of concern identified on
      screening mammograms to improve specificity of the screening system and reduce
      biopsies performed on negative lesions. With new breast imaging techniques and
      modalities constantly emerging, staying current has become difficult. This
      article reviews the role of current and emerging imaging modalities in screening,
      diagnosing, and continued assessment for breast cancer, as well as the currently
      accepted appropriate uses of each.

PMID- 22461354
TI  - Mechanistic insight into the N=N bond-cleavage of azo-compounds that was induced
      by an Al-Al-bonded compound [L(2-)Al(II)-Al(II)L(2-)].
AB  - An alpha-diimine-stabilized Al-Al-bonded compound [L(2-)Al(II)-Al(II)L(2-)] (L =
      [{(2,6-iPr(2)C(6)H(3))NC(Me)}(2)]; 1) consists of dianionic alpha-diimine ligands
      and sub-valent Al(2+) ions and thus could potentially behave as a multielectron
      reductant. The reactions of compound 1 with azo-compounds afforded phenylimido
      bridged products [L(-)Al(III)(MU(2)-NPh)(MU(2)-NAr)Al(III)L(-)] (2-4). During the
      reaction, the dianionic ligands and Al(2+) ions were oxidized into monoanions and
      Al(3+), respectively, whilst the [NAr](2-) imides were produced by the four
      electron reductive cleavage of the N=N double bond. Upon further reduction by Na,
      the monoanionic ligands in compound 2 were reduced to the dianion to give [(L(2
      ))(2)Al(III)(2)(MU(2)-NPh)(2)Na(2)(thf)(4)] (5). Interestingly, when asymmetric
      azo-compounds were used, the asymmetric adducts were isolated as the only
      products (compounds 3 and 4). DFT calculations indicated that the reaction was
      quite feasible in the singlet electronic state, but the final product with the
      triplet-state monoanionic ligands could result from an exothermic singlet-to
      triplet conversion during the reaction process.

PMID- 22461355
TI  - (Lysozyme type VI)-stabilized Au8 clusters: synthesis mechanism and application
      for sensing of glutathione in a single drop of blood.
AB  - This paper presents a one-pot approach for preparing highly fluorescent Au(8) 
      clusters by reacting the Au(3+)  precursor solution with lysozyme type VI (Lys
      VI) at pH 3. The fluorescence band of (Lys VI)-stabilized Au(8)  clusters is
      centered at 455 nm on the excitation at 380 nm. Blue-emitting Au(8)  clusters
      have a high quantum yield (~56%), two fluorescence lifetimes, and a rare amount
      of Au(+)  on the surface of the Au core. When the pH of a solution of Au(8) 
      clusters increases suddenly to 12, the Au(8)  clusters gradually convert to
      Au(25)  clusters over time. This conversion is also observed in the case of (Lys
      VI)-directed synthesis of Au(25)  clusters at pH 12. The pH-induced conversion of
      Au(8)  to Au(25)  clusters suggests that the size of (Lys VI)-stabilized gold
      nanoclusters (AuNCs) relies on the secondary structure of Lys VI, which is
      susceptible to pH change. Based on these results and previous literature, this
      paper proposes the possible mechanism for growing (Lys VI)-stabilized Au(8)  and
      Au(25)  clusters. Additionally, (Lys VI)-stabilized Au(8)  clusters could sense
      glutathione (GSH) through GSH-induced core-etching of Au(8)  clusters; the limit
      of detection at a signal-to-noise ratio of 3 for GSH is determined to be 20 nm.
      Except for cysteine, the selectivity of (Lys VI)-stabilized Au(8)  clusters for
      GSH over amino acids is remarkably high. The practicality of using Au(8) 
      clusters to determine the concentration of GSH in a single drop of blood is also
      validated.

PMID- 22461356
TI  - Physical activity vs. sedentary time: independent associations with adiposity in
      children.
AB  - OBJECTIVE: To investigate the independent associations between objectively
      measured levels of movement intensity (i.e., time spent sedentary and at light,
      moderate and vigorous intensities) and indicators of adiposity in a cohort of
      Canadian children. METHODS: A cross-sectional study was conducted in 550
      Caucasian children aged 8-10 years with at least one obese biological parent.
      Physical activity and sedentary time (accelerometer over 7 d) and indicators of
      adiposity (% body fat measured by dual-energy X-ray absorptiometry and waist-to
      height ratio) were objectively measured. We examined the associations between
      levels of movement intensity and adiposity in multi-level linear regression
      models adjusted for age, sex, sleep duration, energy intake, sexual maturation,
      parental socioeconomic status and parental body mass index. RESULTS: Objectively
      measured sedentary time was not associated with adiposity indicators in this
      cohort (unadjusted and adjusted models). However, moderate-to-vigorous physical
      activity (MVPA) was inversely associated with % body fat (adj. beta = -0.047; P =
      0.02) and waist-to-height ratio (adj. beta = -0.071; P < 0.001), independent of
      sedentary time and other covariates. Additionally, we observed that children who
      did not accumulate >=60 min d(-1) of MVPA were more likely to be overweight or
      obese compared to those who met the recommendation (odds ratio [OR] 2.22, 95%
      confidence interval [CI] 1.45-3.38). In contrast, there was no difference in the
      likelihood of being categorized as overweight or obese between those who met the
      recommendation of <=2 h d(-1) of screen time and those who did not meet this
      recommendation (OR 1.27, 95% CI 0.75-2.01). CONCLUSION: The present study
      suggests that MVPA is independently associated with adiposity indices in this
      sample of children while sedentary time is not. Future studies should examine the
      best approach to increase MVPA in children and youth.

PMID- 22461357
TI  - Volumetric intravascular ultrasound assessment of mechanisms and results of stent
      expansion in heart transplant patients.
AB  - BACKGROUND: Percutaneous coronary intervention with stent placement for the
      treatment of patients with cardiac allograft vasculopathy is common, but data
      regarding stent behavior in this setting is lacking. OBJECTIVES: We investigated
      mechanisms and potential differences in stent expansion among transplant patients
      vs. patients with native coronary artery atherosclerotic disease ("controls").
      METHODS: We compared pre- and poststent intravascular ultrasound in 12 transplant
      patients (17 lesions) and 33 control patients (34 lesions) matched according to
      age (60.1 +/- 9.2 years), diabetes mellitus, and lesion location. Planar and
      volumetric analysis was conducted for every 1 mm at the lesion site as well as
      the first 5 mm proximal and distal to the stent edge. Focal stent expansion was
      defined as minimum stent area (MSA) divided by mean reference lumen area. Diffuse
      stent expansion was defined as mean stent area divided by mean reference lumen
      area. RESULTS: Transplant patients had more plaque than "controls" prestenting,
      but similar MSA and focal and diffuse stent expansion afterwards. The increase in
      mean lumen area correlated with the increase in mean vessel area in both groups,
      transplant (R = 0.64, P = 0.008) and controls (R = 0.70, P < 0.0001), but
      correlated inversely with changes in mean plaque area only in the transplant
      group (R = 0.55, P = 0.027). There were no differences in calcification between
      the two groups and no axial plaque distribution from the lesion into the
      reference segments in either group. CONCLUSIONS: The mechanism of stent expansion
      in transplant vasculopathy appears to be similar to de novo atherosclerosis-i.e.,
      mainly vessel expansion to achieve similar acute results.

PMID- 22461358
TI  - Over a hump for imaging atherosclerosis: nanobodies visualize vascular cell
      adhesion molecule-1 in inflamed plaque.

PMID- 22461359
TI  - Epicardium-derived cardiac mesenchymal stem cells: expanding the outer limit of
      heart repair.

PMID- 22461360
TI  - How to obtain a National Heart, Lung, and Blood Institute-sponsored K08 and
      K99/R00 grant in the current funding climate.

PMID- 22461361
TI  - K08 and K99 cardiovascular training: comparisons and trends among current
      awardees.

PMID- 22461364
TI  - A new level of complexity: the role of microRNAs in cardiovascular development.
AB  - The discovery of the regulatory role of noncoding RNAs, and micro (mi)RNAs in
      particular, has added a new layer of complexity to our understanding of
      cardiovascular development. miRNAs regulate and modulate various steps of
      cardiovascular morphogenesis, cell proliferation, differentiation, and phenotype
      modulation. miRNAs simultaneously regulate multiple targets, and many miRNAs can
      bind to the same target, allowing for a complex pattern of regulation of gene
      expression. miRNA families are continuously added during evolution paralleling
      the increased complexity of the cardiovascular system in vertebrates compared
      with invertebrates. Several lines of evidence suggest that the appearance of
      miRNAs is at least in part responsible for the formation of complex organ systems
      and stable regulatory mechanisms in vertebrates. We review the current
      understanding of miRNAs during cardiovascular development. Further progress in
      this area will help to decipher quantitative changes in gene expression that
      provide robustness to cellular phenotypes and regulatory options to diseases
      processes. miRNAs might also provide clues to better understand congenital heart
      defects, which are the most common birth defects in human newborns.

PMID- 22461363
TI  - Nanobodies targeting mouse/human VCAM1 for the nuclear imaging of atherosclerotic
      lesions.
AB  - RATIONALE: A noninvasive tool allowing the detection of vulnerable
      atherosclerotic plaques is highly needed. By combining nanomolar affinities and
      fast blood clearance, nanobodies represent potential radiotracers for
      cardiovascular molecular imaging. Vascular cell adhesion molecule-1 (VCAM1)
      constitutes a relevant target for molecular imaging of atherosclerotic lesions.
      OBJECTIVE: We aimed to generate, radiolabel, and evaluate anti-VCAM1 nanobodies
      for noninvasive detection of atherosclerotic lesions. METHODS AND RESULTS: Ten
      anti-VCAM1 nanobodies were generated, radiolabeled with technetium-99m, and
      screened in vitro on mouse and human recombinant VCAM1 proteins and endothelial
      cells and in vivo in apolipoprotein E-deficient (ApoE(-/-)) mice. A nontargeting
      control nanobody was used in all experiments to demonstrate specificity. All
      nanobodies displayed nanomolar affinities for murine VCAM1. Flow cytometry
      analyses using human human umbilical vein endothelial cells indicated murine and
      human VCAM1 cross-reactivity for 6 of 10 nanobodies. The lead compound cAbVCAM1-5
      was cross-reactive for human VCAM1 and exhibited high lesion-to-control (4.95+/
      0.85), lesion-to-heart (8.30+/-1.11), and lesion-to-blood ratios (4.32+/-0.48)
      (P<0.05 versus control C57Bl/6J mice). Aortic arch atherosclerotic lesions of
      ApoE(-/-) mice were successfully identified by single-photon emission computed
      tomography imaging. (99m)Tc-cAbVCAM1-5 binding specificity was demonstrated by in
      vivo competition experiments. Autoradiography and immunohistochemistry further
      confirmed cAbVCAM1-5 uptake in VCAM1-positive lesions. CONCLUSIONS: The (99m)Tc
      labeled, anti-VCAM1 nanobody cAbVCAM1-5 allowed noninvasive detection of VCAM1
      expression and displayed mouse and human cross-reactivity. Therefore, this study
      demonstrates the potential of nanobodies as a new class of radiotracers for
      cardiovascular applications. The nanobody technology might evolve into an
      important research tool for targeted imaging of atherosclerotic lesions and has
      the potential for fast clinical translation.

PMID- 22461362
TI  - Elucidating nature's solutions to heart, lung, and blood diseases and sleep
      disorders.
AB  - Evolution has provided a number of animal species with extraordinary phenotypes.
      Several of these phenotypes allow species to survive and thrive in environmental
      conditions that mimic disease states in humans. The study of evolved mechanisms
      responsible for these phenotypes may provide insights into the basis of human
      disease and guide the design of new therapeutic approaches. Examples include
      species that tolerate acute or chronic hypoxemia like deep-diving mammals and
      high-altitude inhabitants, as well as those that hibernate and interrupt their
      development when exposed to adverse environments. The evolved traits exhibited by
      these animal species involve modifications of common biological pathways that
      affect metabolic regulation, organ function, antioxidant defenses, and oxygen
      transport. In 2006, the National Heart, Lung, and Blood Institute released a
      funding opportunity announcement to support studies that were designed to
      elucidate the natural molecular and cellular mechanisms of adaptation in species
      that tolerate extreme environmental conditions. The rationale for this funding
      opportunity is detailed in this article, and the specific evolved mechanisms
      examined in the supported research are described. Also highlighted are past
      medical advances achieved through the study of animal species that have evolved
      extraordinary phenotypes as well as the expectations for new understanding of
      nature's solutions to heart, lung, blood, and sleep disorders through future
      research in this area.

PMID- 22461365
TI  - MicroRNAs and stem cells: control of pluripotency, reprogramming, and lineage
      commitment.
AB  - Stem cells hold great promise for regenerative medicine and the treatment of
      cardiovascular diseases. The mechanisms regulating self-renewal, pluripotency,
      and differentiation are not fully understood. MicroRNAs (miRs) are small
      noncoding RNAs controlling gene expression, either by inducing mRNA degradation
      or by blocking mRNA translation. The expression of miRs was shown to regulate
      various aspects of stem cell functions, including the maintenance and induction
      of pluripotency for reprogramming. In addition, some miRs control cell fate
      decisions. This review summarizes the role of miRs in reprogramming and embryonic
      stem cell self-renewal, and specifically addresses the regulation of
      cardiovascular cell fate decisions by miRs.

PMID- 22461366
TI  - Importance of myocyte-nonmyocyte interactions in cardiac development and disease.
AB  - Emerging data in the field of cardiac development as well as repair and
      regeneration indicate a complex and important interplay between endocardial,
      epicardial, and myofibroblast populations that is critical for cardiomyocyte
      differentiation and postnatal function. For example, epicardial cells have been
      shown to generate cardiac myofibroblasts and may be one of the primary sources
      for this cell lineage during development. Moreover, paracrine signaling from the
      epicardium and endocardium is critical for proper development of the heart and
      pathways such as Wnt, fibroblast growth factor, and retinoic acid signaling have
      been shown to be key players in this process. Despite this progress, interactions
      between nonmyocyte cells and cardiomyocytes in the heart are still poorly
      understood. We review the various nonmyocyte-myocyte interactions that occur in
      the heart and how these interactions, primarily through signaling networks, help
      direct cardiomyocyte differentiation and regulate postnatal cardiac function.

PMID- 22461367
TI  - Genetic variation in vascular endothelial growth factor-a and lung function.
AB  - RATIONALE: Given the role of vascular endothelial growth factor (VEGF) in lung
      development, we hypothesized that polymorphisms in VEGF-A may be associated with
      lung function. OBJECTIVES: The current study was designed to assess the role of
      genetic variants in VEGF-A as determinants of airway function from infancy
      through early adulthood. METHODS: Association between five single-nucleotide
      polymorphisms (SNPs) in VEGF-A and lung function were assessed longitudinally in
      two unselected birth cohorts and cross-sectionally among infants. Replication
      with two SNPs was conducted in adults and children with asthma. We investigated
      the functionality of the SNP most consistently associated with lung function
      (rs3025028) using Western blotting to measure the ratio of plasma VEGF
      A(165b)/panVEGF-A(165) among homozygotes. MEASUREMENTS AND MAIN RESULTS: In two
      populations in infancy, C-allele homozygotes of rs3025028 had significantly
      higher VmaxFRC, forced expiratory flow(50), and forced expiratory flow(25-75)
      compared with other genotype groups. Among preschool children (age 3 yr), C
      allele of rs3025028 was associated with significantly higher specific airway
      conductance, with similar findings observed for lung function in school-age
      children. For FEV(1)/FVC ratio similar findings were observed among adolescents
      and young adults (birth cohort), and then replicated in adults and schoolchildren
      with asthma (cross-sectional studies). For rs3025038, plasma VEGF-A(165b)/panVEGF
      A(165) was significantly higher among CC versus GG homozygotes (P <= 0.02) at
      birth, in school-age children, and in adults. CONCLUSIONS: We report significant
      associations between VEGF-A SNP rs3025028 and parameters of airway function
      measured throughout childhood, with the effect persisting into adulthood. We
      propose that the mechanism may be mediated through the ratios of active and
      inhibitory isoforms of VEGF-A(165), which may be determined by alternative
      splicing.

PMID- 22461368
TI  - Receptor of activated protein C promotes metastasis and correlates with clinical
      outcome in lung adenocarcinoma.
AB  - RATIONALE: Efficient metastasis requires survival and adaptation of tumor cells
      to stringent conditions imposed by the extracellular milieu. Identification of
      critical survival signaling pathways in tumor cells might unveil novel targets
      relevant in disease progression. OBJECTIVES: To investigate the contribution of
      activated protein C (APC) and its receptor (endothelial protein C receptor
      [EPCR]) in animal models of lung cancer metastasis and in patients with lung
      adenocarcinoma. METHODS: Signaling pathway triggered by APC/EPCR and its
      relevance in apoptosis was studied in vitro. Functional significance was assessed
      by silencing and blocking antibodies in several in vivo models of lung cancer
      metastasis in athymic nude Foxn1(nu) mice. We examined EPCR levels using a
      microarray dataset of 107 patients. Immunohistochemical analysis was performed in
      an independent cohort of 295 patients with lung adenocarcinoma. MEASUREMENTS AND
      MAIN RESULTS: The effects of APC binding to EPCR rapidly triggered Akt and
      extracellular signal-regulated kinase signaling pathways, leading to attenuated
      in vitro apoptosis. In vivo, silencing of EPCR expression or blocking APC/EPCR
      interaction reduced infiltration in the target organ, resulting in impaired
      prometastatic activity. Moreover, overexpression of EPCR induced an increased
      metastatic activity to target organs. Analysis of clinical samples showed a
      robust association between high EPCR levels and poor prognosis, particularly in
      stage I patients. CONCLUSIONS: EPCR and its ligand APC promote cell survival that
      contributes to tumor cell endurance to stress favoring prometastatic activity of
      lung adenocarcinoma. EPCR/APC is a novel target of relevance in the clinical
      outcome of early-stage lung cancer.

PMID- 22461370
TI  - Interaction between asthma and lung function growth in early life.
AB  - RATIONALE: The causal direction between asthma and lung function deficit is
      unknown, but important for the focus of preventive measures and research into the
      origins of asthma. OBJECTIVES: To analyze the interaction between lung function
      development and asthma from birth to 7 years of age. METHODS: The Copenhagen
      Prospective Studies on Asthma in Childhood is a prospective clinical study of a
      birth cohort of 411 at-risk children. Spirometry was completed in 403 (98%)
      neonates and again by age 7 in 317 children (77%). MEASUREMENTS AND MAIN RESULTS:
      Neonatal spirometry and bronchial responsiveness to methacholine was measured
      during sedation by forced flow-volume measurements. Asthma was diagnosed
      prospectively from daily diary cards and clinic visits every 6 months. Children
      with asthma by age 7 (14%) already had a significant airflow deficit as neonates
      (forced expiratory flow at 50% of vital capacity second in neonates reduced by
      0.34 z score by 1 mo; P = 0.03). This deficit progressed significantly during
      early childhood (forced expiratory flow at 0.5 seconds in neonates at age 7
      reduced by 0.82 z score by age 7; P < 0.0001), suggesting that approximately 40%
      of the airflow deficit associated with asthma is present at birth, whereas 60%
      develops with clinical disease. Environmental tobacco exposure, but not allergic
      sensitization, also hampered airflow growth. Bronchial responsiveness to
      methacholine in the neonates was associated with the development of asthma (P =
      0.01). CONCLUSIONS: Children developing asthma by age 7 had a lung function
      deficit and increased bronchial responsiveness as neonates. This lung function
      deficit progressed to age 7. Therefore, research into the origins and prevention
      of asthma should consider early life before and after birth.

PMID- 22461371
TI  - Is it possible to obtain a presurgical Lasmar score for hysteroscopic myomectomy
      by ultrasound alone?
AB  - OBJECTIVE: To determine whether a Lasmar score obtained entirely by the use of
      two-dimensional (2D) and three-dimensional (3D) ultrasound provides results
      similar to those obtained using the original hysteroscopic technique. METHODS:
      This was a prospective study performed on a series of patients presenting with
      symptomatic submucous fibroids and scheduled for hysteroscopic myomectomy.
      Ultrasound Lasmar scores were obtained by a single physician, a specialist in
      ultrasonography, in the luteal phase of the menstrual cycle. 3D images were
      evaluated by offline examination using multiplanar analysis. Classical Lasmar
      scores were obtained by a different physician, a specialist in hysteroscopy,
      during the follicular phase of the subsequent cycle. Surgery was performed by a
      third physician in the follicular phase who also reported a Lasmar score, which
      we considered as the gold standard. The concordance between group classifications
      (I-III, relating to difficulty of hysteroscopic resection) according to the three
      methods used to obtain the Lasmar score (ultrasound, classical and surgery) was
      calculated using Cohen's kappa statistic. RESULTS: Thirty-four women, with a mean
      age of 43 +/- 4.9 years, were enrolled in the study. Thirty-six submucous
      fibroids were identified by both ultrasound and diagnostic hysteroscopy. The mean
      diameter of fibroids evaluated was 28 +/- 13.2 mm. The concordance between the
      three methods of classifying patients according to Lasmar score was high:
      classical vs. surgery, kappa = 0.88; ultrasound vs. surgery, kappa = 0.93; and
      classical vs. ultrasound, kappa = 0.77. CONCLUSION: The Lasmar score can be
      obtained solely by ultrasound examination performed in the luteal phase of the
      menstrual cycle, avoiding office hysteroscopy without a loss of diagnostic
      accuracy.

PMID- 22461369
TI  - Inflammasome-regulated cytokines are critical mediators of acute lung injury.
AB  - RATIONALE: Despite advances in clinical management, there are currently no
      reliable diagnostic and therapeutic targets for acute respiratory distress
      syndrome (ARDS). The inflammasome/caspase-1 pathway regulates the maturation and
      secretion of proinflammatory cytokines (e.g., IL-18). IL-18 is associated with
      injury in animal models of systemic inflammation. OBJECTIVES: We sought to
      determine the contribution of the inflammasome pathway in experimental acute lung
      injury and human ARDS. METHODS: We performed comprehensive gene expression
      profiling on peripheral blood from patients with critical illness. Gene
      expression changes were assessed using real-time polymerase chain reaction, and
      IL-18 levels were measured in the plasma of the critically ill patients. Wild
      type mice or mice genetically deficient in IL-18 or caspase-1 were mechanically
      ventilated using moderate tidal volume (12 ml/kg). Lung injury parameters were
      assessed in lung tissue, serum, and bronchoalveolar lavage fluid. MEASUREMENTS
      AND MAIN RESULTS: In mice, mechanical ventilation enhanced IL-18 levels in the
      lung, serum, and bronchoalveolar lavage fluid. IL-18-neutralizing antibody
      treatment, or genetic deletion of IL-18 or caspase-1, reduced lung injury in
      response to mechanical ventilation. In human patients with ARDS, inflammasome
      related mRNA transcripts (CASP1, IL1B, and IL18) were increased in peripheral
      blood. In samples from four clinical centers, IL-18 was elevated in the plasma of
      patients with ARDS (sepsis or trauma-induced ARDS) and served as a novel
      biomarker of intensive care unit morbidity and mortality. CONCLUSIONS: The
      inflammasome pathway and its downstream cytokines play critical roles in ARDS
      development.

PMID- 22461372
TI  - Altered white matter connectivity in never-medicated patients with schizophrenia.
AB  - Numerous diffusion tensor imaging (DTI) studies have implicated white matter
      brain tissue abnormalities in schizophrenia. However, the vast majority of these
      studies included patient populations that use antipsychotic medication. Previous
      research showed that medication intake can affect brain morphology and the
      question therefore arises to what extent the reported white matter aberrations
      can be attributed to the disease rather than to the use of medication. In this
      study we included 16 medication-naive patients with schizophrenia and compared
      them to 23 healthy controls to exclude antipsychotic medication use as a
      confounding factor. For each subject DTI scans and magnetization transfer imaging
      (MTI) scans were acquired. A new tract-based analysis was used that combines
      fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer
      ratio (MTR) to examine group differences in 12 major white matter fiber bundles.
      Significant group differences in combined FA, MD, MTR values were found for the
      right uncinate fasciculus and the left arcuate fasciculus. Additional analysis
      revealed that the largest part of both tracts showed an increase in MTR in
      combination with an increase in MD for patients with schizophrenia. We interpret
      these group-related differences as disease-related axonal or glial aberrations
      that cannot be attributed to antipsychotic medication use.

PMID- 22461373
TI  - Experimental and theoretical studies on the synthesis, spectroscopic data, and
      reactions of formyl azide.

PMID- 22461374
TI  - Targeted exome sequencing in clear cell renal cell carcinoma tumors suggests
      aberrant chromatin regulation as a crucial step in ccRCC development.
AB  - Clear cell renal cell carcinomas are characterized by 3p loss, and by
      inactivation of Von Hippel Lindau (VHL), a tumorsuppressor gene located at 3p25.
      Recently, SETD2, located at 3p21, was identified as a new candidate ccRCC tumor
      suppressor gene. The combined mutational frequency in ccRCC tumors of VHL and
      SETD2 suggests that there are still undiscovered tumor-suppressor genes on 3p. We
      screened all genes on 3p for mutations in 10 primary ccRCC tumors using exome
      sequencing. We identified inactivating mutations in VHL, PBRM1, and BAP1.
      Sequencing of PBRM1 in ccRCC-derived cell lines confirmed its frequent
      inactivation in ccRCC. PBRM1 encodes for BAF180, the chromatin targeting subunit
      of the SWI/SNF complex. BAP1 encodes for BRCA1 associated protein-1, involved in
      histone deubiquitination. Taken together, the accumulating data suggest an
      important role for aberrant chromatin regulation in ccRCC development.

PMID- 22461376
TI  - Polychloride monoanions from [Cl3]- to [Cl9]- : a Raman spectroscopic and quantum
      chemical investigation.
AB  - Polychloride monoanions stabilized by quaternary ammonium salts are investigated
      using Raman spectroscopy and state-of-the-art quantum-chemical calculations. A
      regular V-shaped pentachloride is characterized for the [N(Me)(4)][Cl(5)] salt,
      whereas a hockey-stick-like structure is tentatively assigned for
      [N(Et)(4)][Cl(2)???Cl(3)(-)]. Increasing the size of the cation to the quaternary
      ammonium salts [NPr(4)](+) and [NBu(4)](+) leads to the formation of the [Cl(3)](
      ) anion. The latter is found to be a pale yellow liquid at about 40  degrees C,
      whereas all the other compounds exist as powders. Further to these observations,
      the novel [Cl(9)](-) anion is characterized by low-temperature Raman spectroscopy
      in conjunction with quantum-chemical calculations.

PMID- 22461375
TI  - Cardiovascular risk factors in multi-ethnic middle school students: the HEALTHY
      primary prevention trial.
AB  - OBJECTIVE: The objective of this study was to examine the effects of an
      integrated, multi-component, school-based intervention programme on
      cardiovascular disease (CVD) risk factors among a multi-ethnic cohort of middle
      school students. METHODS: HEALTHY was a cluster randomized, controlled, primary
      prevention trial. Middle school was the unit of randomization and intervention.
      Half of the schools were assigned to an intervention programme consisting of
      changes in the total school food environment and physical education classes,
      enhanced by educational outreach and behaviour change activities and promoted by
      a social marketing campaign consisting of reinforcing messages and images.
      Outcome data reported (anthropometrics, blood pressure and fasting lipid levels)
      were collected on a cohort of students enrolled at the start of 6th grade (~11-12
      years old) and followed to end of 8th grade (~13-14 years old). RESULTS: Forty
      two middle schools were enrolled at seven field centres; 4363 students provided
      both informed consent and CVD data at baseline and end of study. The sample was
      52.7% female, 54.5% Hispanic, 17.6% non-Hispanic Black, 19.4% non-Hispanic White
      and 8.5% other racial/ethnic combinations, and 49.6% were categorized as
      overweight or obese (body mass index >= 85th percentile) at baseline. A
      significant intervention effect was detected in the prevalence of hypertension in
      non-Hispanic Black and White males. The intervention produced no significant
      changes in lipid levels. CONCLUSIONS: The prevalence of some CVD risk factors is
      high in minority middle school youth, particularly males. A multi-component,
      school-based programme achieved only modest reductions in these risk factors;
      however, promising findings occurred in non-Hispanic Black and White males with
      hypertension.

PMID- 22461377
TI  - Photolytic versus microbial degradation of clomazone in a flooded California rice
      field soil.
AB  - BACKGROUND: Clomazone is a popular herbicide used on California rice fields and
      exhibits rapid anaerobic microbial degradation (t(1/2) = 7.9 days). To test the
      potential of direct and indirect photolytic degradation as a cofactor in the
      overall degradation rate, sacrificial time-series microcosms were amended with
      water, non-sterilized soil + water and sterilized soil + water. Clomazone was
      added to each microcosm, which was then exposed to natural and artificial
      sunlight over 35 days. Water and acetonitrile extracts were analyzed for
      clomazone and metabolites via LC/MS/MS. RESULTS: The calculated pseudo-first
      order degradation rate constants (k) were k(water) = 0-0.005 +/- 0.003 day(-1) ,
      k(sterile) = 0-0.005 +/- 0.003 day(-1) and k(non-sterile) = 0.010 +/- 0.002-0.044
      +/- 0.007 day(-1) , depending on light type. The formation of ring-open
      clomazone, a microbial metabolite, correlated with clomazone degradation. Trace
      amounts of 5-hydroxyclomazone (m/z = 256 -> 125), aromatic hydroxyclomazone (m/z
      = 256 -> 141) and an unknown product (m/z = 268 -> 125) were observed.
      CONCLUSIONS: The photolytic degradation rate depends on both light type and the
      quality of the chromophores that induce indirect photolysis. Microbial
      degradation was found to be sensitive to temperature fluctuations. Overall,
      microbes are shown to be more detrimental to the environmental fate of clomazone
      than photolysis.

PMID- 22461378
TI  - Ultrasensitive colorimetric DNA detection using a combination of rolling circle
      amplification and nicking endonuclease-assisted nanoparticle amplification
      (NEANA).
AB  - A combination of rolling circle amplification and nicking endonuclease-assisted
      nanoparticle amplification (NEANA) is used for the rapid, colorimetric detection
      of DNA. The integration of rolling circle amplification into the NEANA approach
      allows for detection of oligonucleotides with arbitrary sequences at ultralow
      concentrations.

PMID- 22461379
TI  - Fetal left brachiocephalic vein in normal and abnormal conditions.
AB  - OBJECTIVES: To establish values of fetal left brachiocephalic vein (LBCV)
      dimensions during normal pregnancy and determine whether routine assessment of
      the LBCV may help in identifying fetuses with congenital abnormalities of this
      vessel. METHODS: Fetal LBCV was assessed prospectively during ultrasound
      examinations in 431 normal singleton pregnancies. The visualization rate of the
      transverse view of the upper fetal chest at the level of drainage of the LBCV
      into the superior vena cava (SVC) by two-dimensional (2D) and 2D plus color
      Doppler ultrasound was evaluated. Reference ranges of LBCV diameter during non
      complicated pregnancies were established. Interobserver and intraobserver
      measurement variability was analyzed. In addition, a retrospective review of the
      hospital medical records of 91 pregnancies with fetuses diagnosed with LBCV
      abnormalities was performed. RESULTS: Sonographic assessment of the fetal LBCV
      was consistently achieved in the second and third trimesters and in some fetuses
      in the first trimester of pregnancy. In normal fetuses LBCV diameter increased
      significantly throughout pregnancy, with a mean value of 0.7 mm at 11 weeks and
      4.9 mm at term. Dilation of the fetal LBCV was noted in five cases of
      intracranial arteriovenous malformation and six cases of supracardiac type total
      anomalous pulmonary venous connection. Abnormal course of the LBCV was noted in
      12 fetuses. In 63 fetuses with a persistent left SVC and a right SVC the LBCV was
      absent. CONCLUSION: This is the first study describing an effective sonographic
      approach for the assessment of fetal LBCV dimensions during pregnancy. The
      normative data may provide an additional means of detecting rare anomalies of
      systemic and pulmonary veins during pregnancy.

PMID- 22461380
TI  - Resting-state functional MRI: functional connectivity analysis of the visual
      cortex in primary open-angle glaucoma patients.
AB  - PURPOSE: To analyze functional connectivity (FC) of the visual cortex using
      resting-state functional MRI in human primary open-angle glaucoma (POAG)
      patients. MATERIALS AND METHODS: Twenty-two patients with known POAG and 22 age
      matched controls were included in this IRB-approved study. Subjects were
      evaluated by 3 T MR using resting-state blood oxygenation level dependent and
      three-dimensional brain volume imaging (3D-BRAVO) MRI. Data processing was
      performed with standard software. FC maps were generated from Brodmann areas (BA)
      17/18/19/7 in a voxel-wise fashion. Region of interest analysis was used to
      specifically examine FC among each pair of BA17/18/19/7. RESULTS: Voxel-wise
      analyses demonstrated decreased FC in the POAG group between the primary visual
      cortex (BA17) and the right inferior temporal, left fusiform, left middle
      occipital, right superior occipital, left postcentral, right precentral gyri, and
      anterior lobe of the left cerebellum. Increased FC was found between BA17 and the
      left cerebellum, right middle cerebellar peduncle, right middle frontal gyrus,
      and extra-nuclear gyrus (P < 0.05). In terms of the higher visual cortices
      (BA18/19), positive FC was disappeared with the cerebellar vermis, right middle
      temporal, and right superior temporal gyri (P < 0.05). Negative FC was
      disappeared between BA18/19 and the right insular gyrus (P < 0.05). Region of
      interest analysis demonstrated no statistically significant differences in FC
      between the POAG patients relative to the controls (P > 0.05). CONCLUSION:
      Changes in FC of the visual cortex are found in patients with POAG. These include
      alterations in connectivity between the visual cortex and associative visual
      areas along with disrupted connectivity between the primary and higher visual
      areas.

PMID- 22461381
TI  - Pseudoephenamine: a practical chiral auxiliary for asymmetric synthesis.

PMID- 22461382
TI  - Systematic analysis and functional annotation of variations in the genome of an
      Indian individual.
AB  - Whole genome sequencing of personal genomes has revealed a large repertoire of
      genomic variations and has provided a rich template for identification of common
      and rare variants in genomes in addition to understanding the genetic basis of
      diseases. The widespread application of personal genome sequencing in clinical
      settings for predictive and preventive medicine has been limited due to the lack
      of comprehensive computational analysis pipelines. We have used next-generation
      sequencing technology to sequence the whole genome of a self-declared healthy
      male of Indian origin. We have generated around 28X of the reference human genome
      with over 99% coverage. Analysis revealed over 3 million single nucleotide
      variations and about 490,000 small insertion-deletion events including several
      novel variants. Using this dataset as a template, we designed a comprehensive
      computational analysis pipeline for the systematic analysis and annotation of
      functionally relevant variants in the genome. This study follows a systematic and
      intuitive data analysis workflow to annotate genome variations and its potential
      functional effects. Moreover, we integrate predictive analysis of pharmacogenomic
      traits with emphasis on drugs for which pharmacogenomic testing has been
      recommended. This study thus provides the template for genome-scale analysis of
      personal genomes for personalized medicine.

PMID- 22461383
TI  - Quantitative structure-activity relationships of monoterpenoid binding activities
      to the housefly GABA receptor.
AB  - BACKGROUND: Monoterpenoids are a large group of plant secondary metabolites. Many
      of these naturally occurring compounds have shown good insecticidal potency on
      pest insects. Previous studies in this laboratory have indicated that some
      monoterpenoids have positive modulatory effects on insect GABA receptors. In this
      study, the key properties of monoterpenoids involved in monoterpenoid binding
      activity at the housefly GABA receptor were determined by developing quantitative
      structure-activity relationship (QSAR) models, and the relationship between the
      toxicities of these monoterpenoids and their GABA receptor binding activities was
      evaluated. RESULTS: Two QSAR models were determined for nine monoterpenoids
      showing significant effects on [3H]-TBOB binding and for nine p-menthane analogs
      with at least one oxygen atom attached to the ring. The Mulliken charges on
      certain carbon atoms, the log P value and the total energy showed significant
      relationships with binding activities to the housefly GABA receptor in these two
      QSAR models. CONCLUSIONS: From the QSAR models, some chemical and structural
      parameters, including the electronic properties, hydrophobicity and stability of
      monoterpenoid molecules, were suggested to be strongly involved in binding
      activities to the housefly GABA receptor. These findings will help to understand
      the mode of action of these natural insecticides, and provide guidance to predict
      more monoterpenoid insecticides.

PMID- 22461384
TI  - Overweight and obese teenagers: why is adolescence a critical period?
AB  - This paper discusses the critical period of adolescence and its potential role in
      the development and persistence of obesity. The adolescent years are
      characteristic of changes in body composition (location and quantity of body
      fat), physical fitness and decreased insulin sensitivity during puberty. This
      period of growth and maturation is also marked with behavioural changes in diet,
      physical activity, sedentary behaviour and psychological health. Physical
      activity and sport participation decline during adolescence especially in teenage
      girls, while sedentary behaviour, risk for depression and body esteem issues
      increase during the teenage years. These physiological and behavioural changes
      during adolescence warrant the attention of health practitioners to prevent the
      onset and continuation of obesity throughout the lifespan.

PMID- 22461386
TI  - Carbon-decorated single-crystalline Ni2P nanotubes derived from ni nanowire
      templates: a high-performance material for Li-ion batteries.
AB  - Single-crystalline Ni(2)P nanotubes (NTs) were facilely synthesized by using a Ni
      nanowire template. The mechanism for the formation of the tubular structures was
      related to the nanoscale Kirkendall effect. These NTs exhibited a core/shell
      structure with an amorphous carbon layer that was grown in situ by employing
      oleylamine as a capping agent. Galvanostatic charge/discharge measurements
      indicated that these Ni(2)P/C NTs exhibited superior high-rate capability and
      good cycling stability. There was still about 310 mA h  g(-1) retained after 100
      cycles at a rate of 5 C. Importantly, the tubular nanostructures and the single
      crystalline nature of the Ni(2)P NTs were also preserved after prolonged cycling
      at a relatively high rate. These improvements were attributed to the stable
      nanotubular structure of Ni(2)P and the carbon shell, which enhanced the
      conductivity of Ni(2)P, suppressed the aggregation of active particles, and
      increased the electrode stability during cycling.

PMID- 22461385
TI  - MicroRNA degradation and turnover: regulating the regulators.
AB  - MicroRNAs (miRNAs) are endogenous, small noncoding RNAs that play important
      regulatory roles in gene expression. The control of miRNA biogenesis has been
      well characterized, but their degradation is not fully understood. Recent
      discoveries indicate that miRNAs have a long life span in general. However, rapid
      turnover dynamics of miRNAs in a variety of specific cellular contexts has been
      documented, as well as the requirement of sequence elements for miRNA decay.
      Furthermore, several ribonucleases that degrade miRNAs have been identified.
      Here, we discuss the cellular contexts and biochemical mechanisms of miRNA decay,
      together with several prominent questions in this field.

PMID- 22461387
TI  - Uncoupling protein-2 protects endothelial function in diet-induced obese mice.
AB  - RATIONALE: Previous studies indicate uncoupling protein-2 (UCP2) as an
      antioxidant defense against endothelial dysfunction in hypertension. UCP2 also
      regulates insulin secretion and action. However, the role of UCP2 in endothelial
      dysfunction associated with diabetes and obesity is unclear. OBJECTIVE: UCP2
      protects against endothelial dysfunction induced by high-fat diet through
      inhibition of reactive oxygen species (ROS) production, and subsequent increase
      of nitric oxide bioavailability. METHODS AND RESULTS: Endothelium-dependent
      relaxation (EDR) in aortae and mesenteric arteries in response to acetylcholine
      was measured in wire myograph. Flow-mediated vasodilatation in 2(nd)-order
      mesenteric arteries was measured in pressure myograph. ROS production is measured
      by CM-H(2)DCFDA and DHE fluorescence. High-glucose exposure reduced EDR in mouse
      aortae, which was exaggerated in UCP2 knockout (KO) mice, whereas UCP2
      overexpression by adenoviral infection (AdUCP2) restored the impaired EDR.
      Impairment of EDR and flow-mediated vasodilatation in aortae and mesenteric
      arteries from high-fat diet-induced obese mice (DIO) was exaggerated in UCP2KO
      DIO mice compared with wild-type DIO littermates, whereas AdUCP2 i.v. injection
      restored both EDR and flow-mediated vasodilatation in DIO mice. Improved EDR in
      mesenteric arteries was inhibited by nitric oxide synthase inhibitor. UCP2
      overexpression also inhibited intracellular ROS production in the en face
      endothelium of aorta and mesenteric artery of DIO mice, whereas UCP2 deficiency
      enhanced ROS production. CONCLUSIONS: UCP2 preserves endothelial function through
      increasing nitric oxide bioavailability secondary to the inhibition of ROS
      production in the endothelium of obese diabetic mice.

PMID- 22461389
TI  - Percutaneous endoscopic gastrostomy feeding--a life-saving intervention in SSc
      myositis overlap with pharyngeal dysfunction.

PMID- 22461388
TI  - PAR-2 inhibition reverses experimental pulmonary hypertension.
AB  - RATIONALE: A hallmark of the vascular remodeling process underlying pulmonary
      hypertension (PH) is the aberrant proliferation and migration of pulmonary
      arterial smooth muscle cells (PASMC). Accumulating evidence suggests that mast
      cell mediators play a role in the pathogenesis of PH. OBJECTIVE: In the present
      study we investigated the importance of protease-activated receptor (PAR)-2 and
      its ligand mast cell tryptase in the development of PH. METHODS AND RESULTS: Our
      results revealed strong increase in PAR-2 and tryptase expression in the lungs of
      idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice,
      and monocrotaline (MCT)-treated rats. Elevated tryptase levels were also detected
      in plasma samples from IPAH patients. Hypoxia and platelet-derived growth factor
      (PDGF)-BB upregulated PAR-2 expression in PASMC. This effect was reversed by HIF
      (hypoxia inducible factor)-1alpha depletion, PDGF-BB neutralizing antibody, or
      the PDGF-BB receptor antagonist Imatinib. Attenuation of PAR-2 expression was
      also observed in smooth muscle cells of pulmonary vessels of mice exposed to
      hypoxia and rats challenged with MCT in response to Imatinib treatment. Tryptase
      induced PASMC proliferation and migration as well as enhanced synthesis of
      fibronectin and matrix metalloproteinase-2 in a PAR-2- and ERK1/2-dependent
      manner, suggesting that PAR-2-dependent signaling contributes to vascular
      remodeling by various mechanisms. Furthermore, PAR-2(-/-) mice were protected
      against hypoxia-induced PH, and PAR-2 antagonist application reversed established
      PH in the hypoxia mouse model. CONCLUSIONS: Our study identified a novel role of
      PAR-2 in vascular remodeling in the lung. Interference with this pathway may
      offer novel therapeutic options for the treatment of PH.

PMID- 22461390
TI  - Platinum-based poly(aryleneethynylene) polymers containing thiazolothiazole group
      with high hole mobilities for field-effect transistor applications.
AB  - Two solution-processable platinum-acetylide polymers functionalized with the
      electron-deficient thiazolothiazole spacer are synthesized and show absorption
      features spanning from 320 to 600 nm and optical bandgaps of 2.15 and 2.05 eV.
      The spin-coated polymer thin films of both materials exhibit p-channel field
      effect charge transport characteristics with impressive peak field-effect charge
      carrier mobilities of (2.1-2.8) * 10(-2) cm(2) V(-1) s(-1) and on/off ratios of
      (0.8-1.0) * 10(5) for the holes. The high hole mobility value reported for one of
      the polymers is among the highest reported for metallopolyynes to date. It is
      also shown that the hole mobility can be notably increased by extending the
      conjugation length of the chain from the monothienyl to the bithienyl segment on
      each side of the thiazolothiazole ring.

PMID- 22461392
TI  - Catalytic, atom-economical radical arylation of epoxides.

PMID- 22461393
TI  - The mediating effects of dietary habits on the relationship between television
      viewing and body mass index among youth.
AB  - OBJECTIVE: There is evidence to suggest that excessive television viewing is an
      independent determinant of obesity in young people. However, the pathways between
      television viewing and obesity are not fully understood. Therefore, the purpose
      of this study was to examine whether the relationship between television and body
      mass index (BMI) is mediated by television snacking and junk food consumption.
      METHODS: Results are based on 15,973 youth in grades 6-10 who participated in the
      Canadian 2009/2010 health behaviour in school-aged children survey (HBSC).
      Participants self-reported their weight and height and BMI z-scores were
      calculated based on World Health Organization growth standards. Participants
      reported the frequency of snacking while watching television and the frequency of
      eating junk food (sweets, soft drinks, baked goods, French fries, potato chips).
      Total hours per week of television were calculated. A contemporary multiple
      mediation analysis was used to examine associations. RESULTS: A modest positive
      relationship was observed between television viewing and BMI. The mean BMI z
      score was 0.15 units higher in youth in the highest television viewing quartile
      by comparison with the youth in the lowest quartile. However, contrary to our
      hypothesis, television snacking and junk food consumption were not significant
      positive mediators of the television and BMI relationship. CONCLUSION: The
      pathways between television viewing and obesity are complicated and remain poorly
      understood. Future research using longitudinal or experimental designs, more
      precise measurement tools and formal mediation analyses is needed. This research
      should consider mediators related to both energy intake and expenditure.

PMID- 22461391
TI  - A framework for the analysis of phantom data in multicenter diffusion tensor
      imaging studies.
AB  - Diffusion tensor imaging (DTI) is commonly used for studies of the human brain
      due to its inherent sensitivity to the microstructural architecture of white
      matter. To increase sampling diversity, it is often desirable to perform
      multicenter studies. However, it is likely that the variability of acquired data
      will be greater in multicenter studies than in single-center studies due to the
      added confound of differences between sites. Therefore, careful characterization
      of the contributions to variance in a multicenter study is extremely important
      for meaningful pooling of data from multiple sites. We propose a two-step
      analysis framework for first identifying outlier datasets, followed by a
      parametric variance analysis for identification of intersite and intrasite
      contributions to total variance. This framework is then applied to phantom data
      from the NIH MRI study of normal brain development (PedsMRI). Our results suggest
      that initial outlier identification is extremely important for accurate
      assessment of intersite and intrasite variability, as well as for early
      identification of problems with data acquisition. We recommend the use of the
      presented framework at frequent intervals during the data acquisition phase of
      multicenter DTI studies, which will allow investigators to identify and solve
      problems as they occur.

PMID- 22461395
TI  - Editorial: Enhancing productivity of CHO, plant and algal cells.

PMID- 22461398
TI  - Meeting report: Synthetic DNA - Writing with the Letters of Life: January 24,
      2012, Frankfurt, Germany.
AB  - The one-day meeting on Synthetic DNA (January 24, 2012) organized by and held at
      the DECHEMA in Frankfurt attracted about 100 participants from academia and
      industry interested in synthesizing DNA and its applications in synthetic
      biology. In recent years the cost for synthetic DNA reduced from 7?/bp to
      0.35?/bp which has opened up many new possibilities for molecular biology. You
      can purchase the gene, cDNA, oligo library or full vector specifically for a
      particular expression host and apply synthetic biology principles to produce or
      create new drugs, vaccines or any other biotechnological products. There are,
      however, great concerns within society to produce organisms that do not exist in
      nature, and the potential misuse of them. Adressing these concerns and to use a
      clear terminology that do not cause misunderstandings are important issues within
      the field, which were also discussed at this meeting.

PMID- 22461401
TI  - Saponins show high entomotoxicity by cell membrane permeation in Lepidoptera.
AB  - BACKGROUND: In this study, the effects of three saponins and one sapogenin with a
      triterpenoid or steroid structure in two lepidopteran insect cell lines, ovarian
      Bm5 and midgut CF-203 cells, were analysed with regard to cell viability, cell
      membrane permeation, EcR responsiveness and DNA fragmentation. In addition, the
      entomotoxic action of Q. saponaria saponin with primary midgut cell cultures and
      larval stages of the cotton leafworm Spodoptera littoralis was tested. RESULTS:
      Both lepidopteran cell lines show a high sensitivity to all four sapo(ge)nins,
      with a concentration-dependent viability loss and EC50 values of 25-100 uM in MTT
      bioassays. A trypan blue assay with Q. saponaria saponin confirmed rapid cell
      membrane permeation to be a cause of cytotoxicity. Saponins caused no EcR
      activation in Bm5 cells, but a loss of ecdysteroid signalling was observed with
      IC50 values of 5-10 uM. Lower saponin concentrations induced DNA fragmentation,
      confirming their potential to induce apoptosis. Finally, Q. saponaria saponin
      caused cytotoxicity in primary midgut cell cultures of S. littoralis (EC(50) =
      4.7 uM) and killed 70-84% of S. littoralis larvae at pupation at 30-70 mg g(-1) ,
      while lower concentrations retarded larval weight gain and development.
      CONCLUSIONS: The data obtained provide evidence that saponins exert a strong
      activity on lepidopteran cells, presumably based on a cytotoxic action due to
      permeation of the cell membrane. Primary midgut cell cultures and larvae of S.
      littoralis showed high sensitivity to Q. saponaria saponin, indicating the insect
      midgut as a primary target for entomotoxicity and the potential use of saponins
      in the control of pest Lepidoptera.

PMID- 22461402
TI  - Insertion of an SVA element, a nonautonomous retrotransposon, in PMS2 intron 7 as
      a novel cause of Lynch syndrome.
AB  - Heterozygous germline mutations in the mismatch repair gene PMS2 predispose
      carriers for Lynch syndrome, an autosomal dominant predisposition to cancer.
      Here, we present a LINE-1-mediated retrotranspositional insertion in PMS2 as a
      novel mutation type for Lynch syndrome. This insertion, detected with Southern
      blot analysis in the genomic DNA of the patient, is characterized as a 2.2 kb
      long 5' truncated SVA_F element. The insertion is not detectable by current
      diagnostic testing limited to MLPA and direct Sanger sequencing on genomic DNA.
      The molecular nature of this insertion could only be resolved in RNA from
      cultured lymphocytes in which nonsense-mediated RNA decay was inhibited. Our
      report illustrates the technical problems encountered in the detection of this
      mutation type. Especially large heterozygous insertions will remain unnoticed
      because of preferential amplification of the smaller wild-type allele in genomic
      DNA, and are probably underreported in the mutation spectra of autosomal dominant
      disorders.

PMID- 22461403
TI  - Sonochemical synthesis of Ag/AgCl nanocubes and their efficient visible-light
      driven photocatalytic performance.
AB  - A novel one-step sonochemical approach to synthesize a plasmonic photocatalyst of
      AgCl nanocubes (ca. 115 nm in edge length) with a small amount of Ag metal
      species is presented. The nanoscale Ag/AgCl hybrid photocatalysts with cubic
      morphology are readily formed under ambient ultrasonic conditions and neither
      external heat treatment nor reducing agents are required. The size of the Ag/AgCl
      photocatalysts could be controlled by changing the concentrations of Ag(+) ions
      and polyvinylpyrrolidone molecules in precursor solutions. The compositions,
      microstructures, influencing factors, and possible growth mechanism of the
      Ag/AgCl hybrid nanocubes were systematically investigated. The Ag/AgCl
      photocatalysts show excellent photocatalytic performance for degradation of
      various dye molecules under visible light.

PMID- 22461405
TI  - Embryonic genome activation events in buffalo (Bubalus bubalis) preimplantation
      embryos.
AB  - Embryonic genome activation (EGA) is the first major step towards successful
      initiation of preimplantation development, which culminates in the formation of
      implantation-competent embryos. EGA occurs at species-specific embryonic cell
      stages. In the present work, EGA was identified for buffalo embryos by studying
      the development rate of embryos in normal as well as imposed transcription block
      conditions, analyzing bromo-uridine triphosphate (BrUTP) incorporation rates as
      evidence of de novo transcription initiation, and studying the expression status
      of eukaryotic translation initiation factor 1A (eIF1A), U2 auxiliary splicing
      factor (U2AF), and polyadenylate polymerase (PAP) genes at different embryonic
      cell stages. Under normal, in vitro fertilization and culture conditions, about
      26% and 17% of oocytes could reach morula and blastocyst stages, respectively,
      but no embryos could progress beyond 8-cell stages in presence of alpha-amanitin.
      Culturing embryos in the presence of BrUTP revealed a marked increase in its
      incorporation between 4- and 8-cell stages. All genes studied displayed an abrupt
      increase in expression between 4- and 8-cell stages; PAP expression was
      upregulated earlier from 2- to 4-cell stages. About 65% of PAP transcripts from
      the 4-cell stage and more than 70% of eIF1A, U2AF, and PAP transcripts at 8-cell
      stage embryos were found to be synthesized de novo. Together, these data suggest
      that a minor EGA in buffalo embryos happens from 2- to 4-cell stages, while the
      major EGA takes place from 4- to 8-cell stage transition.

PMID- 22461404
TI  - Connectomics signatures of prenatal cocaine exposure affected adolescent brains.
AB  - Recent in vivo neuroimaging studies revealed that several brain networks are
      altered in prenatal cocaine exposure (PCE) affected adolescent brains. However,
      due to a lack of dense and corresponding cortical landmarks across individuals,
      the systematical alterations of functional connectivities in large-scale brain
      networks and the alteration of structural brain architecture in PCE affected
      brain are largely unknown. In this article, we adopted a newly developed data
      driven strategy to build a large set of cortical landmarks that are consistent
      and corresponding across PCE adolescents and their matched controls. Based on
      these landmarks, we constructed large-scale functional connectomes and applied
      the well-established approaches of deriving genomics signatures in genome-wide
      gene expression studies to discover functional connectomics signatures for the
      characterization of PCE adolescent brains. Results derived from experimental data
      demonstrated that 10 structurally disrupted landmarks were identified in PCE, and
      more importantly, the discovered informative functional connectomics signatures
      among consistent landmarks distinctively differentiate PCE brains from their
      matched controls.

PMID- 22461406
TI  - High-affinity disaccharide binding by tricyclic synthetic lectins.

PMID- 22461409
TI  - Molecular bases for resistance to acetyl-coenzyme A carboxylase inhibitor in
      Japanese foxtail (Alopecurus japonicus).
AB  - BACKGROUND: Haloxyfop-R-methyl is a widely used herbicide to control Poaceae
      weeds. Alopecurus japonicus, a widespread annual grass, can no longer be
      controlled by haloxyfop-R-methyl after continuous use of this herbicide for
      several years. RESULTS: Dose-response experiments have established that the Js-R
      biotype of A. japonicas has evolved resistance to aryloxyphenoxypropionates
      (APPs). Target-site enzyme sensitivity experiments have established that the
      haloxyfop (free acid) rate causing 50% inhibition of acetyl-CoA carboxylase
      (ACCase) activity (I(50)) for the resistant (Js-R) biotype is 11 times higher
      than that for the susceptible (Js-S) biotype. In many cases, resistance to ACCase
      inhibiting herbicides is due to a resistant ACCase enzyme. Full-length DNA and
      mRNA sequences of the plastidic ACCase gene were amplified. Eight single
      nucleotide differences were detected in this region. Four of the nucleotide
      changes were silent mutations. However, the other four nucleotide mutations
      caused four amino acid substitutions, replacing Arg-1734 with Gly, Met-1738 with
      Leu, Thr-1739 with Ser and Ile-2041 with Asn in the R biotype respectively; the
      substitution at position 2041 had been reported, while the other three had not.
      CONCLUSION: The ACCase in the Js-R biotype was less susceptible to haloxyfop-R
      methyl than that in the Js-S biotype. Moreover, the amino acid substitution of
      Ile-2041 with Asn might confer resistance to haloxyfop-R-methyl in A. japonicas.

PMID- 22461410
TI  - Diffusion and birefringence of bioactive dyes in a supramolecular guanosine
      hydrogel.
AB  - Transparent self-standing supramolecular hydrogels were readily prepared by the
      potassium-ion-mediated self-organization of guanosine and 8-bromoguanosine whilst
      the individual components precipitated within a few hours. VT-NMR spectroscopy
      showed that bromoguanosine was a superior gelator compared to guanosine. XRD
      analysis showed that gel formation was caused by stacked G-quartets. AFM analysis
      revealed dendritic architectures of the nanofibers in the two-component hydrogel
      network. DSC profiles showed that the hybrid hydrogels underwent sol-gel
      transition at lower temperature than the pure guanosine and bromoguanosine
      hydrogels. Interestingly, bioactive dyes, such as rose bengal, rhodamine-6-G, and
      fluorescein, could be diffused and released in a controlled manner. UV/Vis
      absorption and fluorescence spectroscopy and CLSM were used to investigate the
      diffusion behavior of dyes in the hydrogel network. These dyes exhibited strong
      birefringence in the gel network (0.07-0.1) as a result of the anisotropic
      organization.

PMID- 22461411
TI  - Correlation assessment among clinical phenotypes, expression analysis and
      molecular modeling of 14 novel variations in the human galactose-1-phosphate
      uridylyltransferase gene.
AB  - Galactose-1-phosphate uridylyltransferase (GALT) catalyzes the conversion of
      galactose-1-phosphate to UDP-galactose, a key step in the galactose metabolism.
      Deficiency of GALT activity in humans caused by deleterious variations in the
      GALT gene can cause a potentially lethal disease called classic galactosemia. In
      this study, we selected 14 novel nucleotide sequence changes in the GALT genes
      found in galactosemic patients for expression analysis and molecular modeling.
      Several variants showed decreased levels of expression and decreased abundance in
      the soluble fraction of the Escherichia coli cell extracts, suggesting altered
      stability and solubility. Only six variant GALT enzymes had detectable enzymatic
      activities. Kinetic studies showed that their V(max)  decreased significantly. To
      further characterize the variants at molecular level, we performed static and
      dynamic molecular modeling studies. Effects of variations on local and/or global
      structural features of the enzyme were anticipated for the majority of variants.
      In-depth studies with molecular dynamic simulations on selected variants
      predicted the alteration of the protein structure even though static models
      apparently did not highlight any perturbation. Overall, these studies offered new
      insights on the molecular properties of GALT enzyme, with the aim of correlating
      them with the clinical outcome. Hum Mutat 33:1107-1115, 2012. (c) 2012 Wiley
      Periodicals, Inc.

PMID- 22461412
TI  - Cerebral somatic pain modulation during autogenic training in fMRI.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) studies are increasingly
      employed in different conscious states. Autogenic training (AT) is a common
      clinically used relaxation method. The purpose of this study was to investigate
      the cerebral modulation of pain activity patterns due to AT and to correlate the
      effects to the degree of experience with AT and strength of stimuli. METHODS:
      Thirteen volunteers familiar with AT were studied with fMRI during painful
      electrical stimulation in a block design alternating between resting state and
      electrical stimulation, both without AT and while employing the same paradigm
      when utilizing their AT abilities. The subjective rating of painful stimulation
      and success in modulation during AT was assessed. RESULTS: During painful
      electrical stimulation without AT, fMRI revealed activation of midcingulate,
      right secondary sensory, right supplementary motor, and insular cortices, the
      right thalamus and left caudate nucleus. In contrast, utilizing AT only
      activation of left insular and supplementary motor cortices was revealed. The
      paired t-test revealed pain-related activation in the midcingulate, posterior
      cingulate and left anterior insular cortices for the condition without AT, and
      activation in the left ventrolateral prefrontal cortex under AT. Activation of
      the posterior cingulate cortex and thalamus correlated with the amplitude of
      electrical stimulation. CONCLUSIONS: This study revealed an effect on cerebral
      pain processing while performing AT. This might represent the cerebral correlate
      of different painful stimulus processing by subjects who are trained in
      performing relaxation techniques. However, due to the absence of a control group,
      further studies are needed to confirm this theory.

PMID- 22461413
TI  - Functional parameters of Dicer-independent microRNA biogenesis.
AB  - Until recently, a Dicer-class RNase III enzyme was believed to be essential for
      microRNA (miRNA) biogenesis in all animals. The conserved vertebrate locus mir
      451 defies this expectation and instead matures by direct cleavage of its pre
      miRNA hairpin via the Slicer activity of Argonaute2 (Ago2). In this study, we
      used structure-function analysis to define the functional parameters of Ago2
      mediated miRNA biogenesis. These include (1) the requirement for base-pairing at
      most, but not all, positions within the pre-mir-451 stem; (2) surprisingly little
      influence of the 5'-nucleotide on Ago sorting; (3) substantial influence of Ago
      protein stoichiometry on mir-451 maturation; (4) strong influence of G:C content
      in the distal stem on 3' resection of cleaved mir-451 substrates; and (5) the
      influence of hairpin length on substrate utilization by Ago2 and Dicer.
      Unexpectedly, we find that certain hairpin lengths confer competence to mature
      via both Dicer-mediated and Ago2-mediated pathways, and we show, in fact, that a
      conventional shRNA can traverse the Dicer-independent pathway. Altogether, these
      data inform the design of effective Dicer-independent substrates for gene
      silencing and reveal novel aspects of substrate handling by Ago proteins.

PMID- 22461415
TI  - The effect of size on the oxygen electroreduction activity of mass-selected
      platinum nanoparticles.

PMID- 22461414
TI  - Effect of glucose concentration during in vitro culture of mouse embryos on
      development to blastocyst, success of embryo transfer, and litter sex ratio.
AB  - A high-glucose concentration in the reproductive tract during early development
      may result in aberrant embryo or fetal development, with effects that could have
      a greater impact on one sex than the other. Here, we determine if a high-glucose
      concentration impacts embryo development and pregnancy outcomes in a sex-specific
      manner in the mouse. Zygotes were cultured in potassium simple optimized medium,
      which typically contains 0.2 mM D-glucose, with and without additional glucose
      supplementation to a concentration of 28 mM. Zygote cleavage and blastocyst rate
      did not differ between treatments, but total and trophectoderm cell counts were
      reduced in blastocysts cultured in a high glucose. No differences between sexes
      nor inner cell mass cell number were observed within each treatment. Blastocysts
      developed in both media were transferred to recipients. The percentage of
      blastocysts resulting in viable pups was significantly reduced when the
      blastocysts were cultured in 28 mM glucose (74 +/- 4%, controls vs. 55.8 +/-
      7.1%, 28 mM glucose), but conceptus loss affected both sexes equally as litter
      sex ratio did not differ between treatments (52.7% and 52.2% males for controls
      and high glucose, respectively). Pup body weight at birth was higher for males
      than females, but was not affected by earlier culture in high glucose. In
      conclusion, in vitro culture in medium with a glucose concentration approximating
      that of diabetic serum reduces total and trophectoderm cell numbers at the
      blastocyst stage and conceptus development to term, but these detrimental effects
      are not sex-specific.

PMID- 22461417
TI  - Reducing residual risk in secondary prevention of cardiovascular disease.

PMID- 22461418
TI  - Elucidation of Mycobacterium tuberculosis type II dehydroquinase inhibitors using
      a fragment elaboration strategy.
AB  - A library of novel Mycobacterium tuberculosis type II dehydroquinase (DHQase)
      inhibitors were discovered through the use of a fragment elaboration approach.
      Putative active site binding fragments were initially assessed in silico which
      led to the selection of two small aromatic fragments for further investigation.
      Synthetic elaboration of the fragments provided a library of 34 inhibitors that
      exhibited low-micromolar inhibition of type II DHQase. A number of these
      inhibitors also showed antibacterial activity in the low-micromolar range in
      screens against M. tuberculosis in vitro; these now serve as lead compounds for
      further development of therapeutics for the treatment of tuberculosis.

PMID- 22461416
TI  - Determinants of residual risk in secondary prevention patients treated with high-
      versus low-dose statin therapy: the Treating to New Targets (TNT) study.
AB  - BACKGROUND: Cardiovascular events occur among statin-treated patients, albeit at
      lower rates. Risk factors for this "residual risk" have not been studied
      comprehensively. We aimed to identify determinants of this risk above and beyond
      lipid-related risk factors. METHODS AND RESULTS: A total of 9251 coronary
      patients with low-density lipoprotein cholesterol <130 mg/dL randomized to double
      blind atorvastatin 10 or 80 mg/d in the Treating to New Targets (TNT) study had
      complete on-treatment 1-year lipid data. Median follow-up was 4.9 years. The
      primary end point was major cardiovascular events (n=729): coronary death,
      nonfatal myocardial infarction, resuscitation after cardiac arrest, or fatal or
      nonfatal stroke. Multivariable determinants of increased risk were older age
      (adjusted hazard ratio [aHR], 1.13 per 1 SD [8.8 years]; 95% confidence interval
      [CI], 1.04-1.23), increased body mass index (aHR, 1.09; 95% CI, 1.02-1.17 per 4.5
      kg/m(2)), male sex (aHR, 1.33; 95% CI, 1.07-1.65), hypertension (aHR, 1.38; 95%
      CI, 1.17-1.63), diabetes mellitus (aHR, 1.33; 95% CI, 1.11-1.60), baseline
      apolipoprotein B (aHR, 1.19; 95% CI, 1.11-1.28 per 19 mg/dL), and blood urea
      nitrogen (aHR, 1.10; 95% CI, 1.03-1.17 per 4.9 mg/dL), in addition to current
      smoking, prior cardiovascular disease, and calcium channel blocker use.
      Determinants of decreased risk were high-dose statin (aHR, 0.82; 95% CI, 0.70
      0.94), aspirin use (aHR, 0.67; 95% CI, 0.56-0.81), and baseline apolipoprotein A
      I (aHR, 0.91; 95% CI, 0.84-0.99 per 25 mg/dL). On-treatment 1-year lipids or
      apolipoproteins were not additionally associated with risk in multivariable
      models. Known baseline variables performed moderately well in discriminating
      future cases from noncases (Harrell c index=0.679). CONCLUSIONS: Determinants of
      residual risk in statin-treated secondary prevention patients included lipid
      related and nonlipid factors such as baseline apolipoproteins, increased body
      mass index, smoking, hypertension, and diabetes mellitus. A multifaceted
      prevention approach should be underscored to address this risk. CLINICAL TRIAL
      REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00327691.

PMID- 22461419
TI  - Amide-based nonheme cobalt(III) olefin epoxidation catalyst: partition of
      multiple active oxidants Co(V)=O, Co(IV)=O, and Co(III)-OO(O)CR.
AB  - A mononuclear nonheme cobalt(III) complex of a tetradentate ligand containing two
      deprotonated amide moieties, [Co(bpc)Cl(2)][Et(4)N] (1; H(2)bpc = 4,5-dichloro
      1,2-bis(2-pyridine-2-carboxamido)benzene), was prepared and then characterized by
      elemental analysis, IR, UV/Vis, and EPR spectroscopy, and X-ray crystallography.
      This nonheme Co(III) complex catalyzes olefin epoxidation upon treatment with
      meta-chloroperbenzoic acid. It is proposed that complex 1 shows partitioning
      between the heterolytic and homolytic cleavage of an O-O bond to afford Co(V)=O
      (3) and Co(IV)=O (4) intermediates, proposed to be responsible for the
      stereospecific olefin epoxidation and radical-type oxidations, respectively.
      Moreover, under extreme conditions, in which the concentration of an active
      substrate is very high, the Co-OOC(O)R (2) species is a possible reactive species
      for epoxidation. Furthermore, partitioning between heterolysis and homolysis of
      the O-O bond of the intermediate 2 might be very sensitive to the nature of the
      solvent, and the O-O bond of the Co-OOC(O)R species might proceed predominantly
      by heterolytic cleavage, even in the presence of small amounts of protic solvent,
      to produce a discrete Co(V) ?O intermediate as the dominant reactive species.
      Evidence for these multiple active oxidants was derived from product analysis,
      the use of peroxyphenylacetic acid as the peracid, and EPR measurements. The
      results suggest that a less accessible Co(V)=O moiety can form in a system in
      which the supporting chelate ligand comprises a mixture of neutral and anionic
      nitrogen donors.

PMID- 22461420
TI  - Effects of ultraviolet B radiation on physicochemical properties of human hair
      shaft.
AB  - Changes in physicochemical properties of the human hair shaft induced by UVB
      during the summer climate were investigated. Using atomic force microscopy and
      thermogravimetric analyzer measurements, we investigated the changes in hair
      shaft physical properties including morphology, roughness, and water content. The
      changes in chemical properties were investigated by using FTIR spectroscopy. Hair
      samples from 20 females without any chemical or physical stresses were
      investigated. The samples were exposed to various UVB doses of 400, 2,000, and
      4,000 mJ/cm(2), which correspond to the radiation times of 0.44, 2.22, and 4.44
      h, respectively. The morphology and surface of the hair shaft was not
      significantly affected by UVB irradiation. The components of keratin were
      affected by the UVB irradiation where the amide A bands at 3,263 and 3,246 cm(-1)
      of the proximal and distal roots, respectively, were shifted to higher band
      region because alpha-helix converted to beta-sheet, and the stretching modes of C
      H lipid alkyl chains at 2,965 and 2,850 cm(-1) in the proximal and distal roots,
      respectively, were developed. As the UVB intensity increased, the water content
      of the proximal root decreased.

PMID- 22461421
TI  - Malformations of the great vessels in the neonatal rat induced by N-(2
      aminoethyl)ethanolamine.
AB  - The reproductive and developmental toxicity of aminoethylethanolamine was
      evaluated in a standard screening study (OECD, 1995: Organisation for economic co
      operation and development. Paris, France), in which groups of Wistar rats
      (10/sex/group) were administered the test substance by gavage at dosage levels of
      50, 250, or 1000 mg/kg/day (groups 2-4, respectively). A control group received
      the vehicle, doubly distilled water. No live pups were delivered in group 4, and
      there was a higher incidence of stillborn offspring and reduced postnatal
      survival in group 3. Macroscopic changes in groups 2 and 3 were primarily related
      to the great vessels and characterized by dilations, aneurysms, and altered
      course of the aorta, pulmonary trunk, carotids, and the ductus arteriosus. A
      follow-up study was conducted to characterize the low dose-response, using dosage
      levels of 0, 0.2, 1, 5, or 50 mg/kg/day (groups 1-5, respectively). Given the
      expected scarcity of the lesions in control offspring, each group consisted of 25
      animals of each sex. Macroscopic examination revealed a high incidence (18.5%) of
      aneurysm-bearing offspring in group 5 litters, and single offspring (0.3-0.4%)
      with aneurysms in groups 3 and 4. Microscopic examination revealed dissecting
      aneurysms in offspring from all aminoethylethanolamine treatment groups, without
      a clear dose-response between groups 2 and 4 (0.6%, 1.2%, and 0.3%,
      respectively), and focal hemorrhages in all groups including the control. In
      comparison, the background incidence of aneurysms in untreated 4-day old
      offspring was 0.2% (Treumann et al., 2011: Toxicol Pathol 39:969-974).
      Consequently, the findings in groups 2-4 cannot be conclusively attributed to
      treatment.

PMID- 22461422
TI  - Selective thoracic ganglionectomy for the treatment of segmental neuropathic
      pain.
AB  - Segmental thoracic neuropathic pain (NeuP) remains particularly difficult to
      treat. Sensory ganglionectomy was reported to alleviate NeuP. The experience with
      thoracic ganglionectomy, however, is very limited. Here, we report the results of
      a prospective pilot study in patients with incapacitating segmental thoracic NeuP
      treated by selective ganglionectomy. Seven patients were included suffering from
      refractory NeuP scoring 8 or more on a visual analogue scale (VAS). Every patient
      had test anaesthesia prior to surgery yielding more than 50% pain relief. The
      spinal ganglion was excised completely via an extraforaminal approach. Mean
      preoperative VAS scores were 9.1 (maximum pain); 5.4 (minimum pain); 7.9 (pain on
      average); 6.9 (pain at the time of presentation); and 7.4 (allodynia). Early post
      operatively, there was a marked improvement of mean scores: 1.7; 0.7; 1.2; 1.0;
      and 0.7, respectively. One patient developed a mild transient hemihypaesthesia.
      In three patients, substantial pain occurred in a formerly unaffected dermatome
      within 1 year. Two of these patients had significant pain relief by a second
      operation. At the time of last follow-up at a mean of 24 months after the first
      procedure, mean VAS scores were 6.3; 2.1; 4.3; 4.0; and 1.3. Overall, medication
      was reduced. The patients rated their outcome as excellent (1), good (2), fair
      (2) and nil (2) with best improvement for allodynia. Selective thoracic
      ganglionectomy is a safe and partially effective procedure in selected patients
      albeit there may be partial recurrence of pain. Recurrent pain may affect
      dermatomes that were not involved initially.

PMID- 22461423
TI  - Thermal bifunctionality of bacterial phenylalanine aminomutase and ammonia lyase
      enzymes.

PMID- 22461424
TI  - Photocurrent enhancement of dye-sensitized solar cells owing to increased dye
      adsorption onto silicon-nanoparticle-coated titanium-dioxide films.
AB  - The inverse-micellar preparation of Si nanoparticles (Nps) was improved by
      utilizing sodium naphthalide. The Si Nps were subsequently functionalized with 4
      vinylbenzoic acid for their attachment onto TiO(2) films of dye-sensitized solar
      cells (DSSCs). The average diameter of the COOH-functionalized Si (Si-COOH) Nps
      was 4.6(+/-1.7) nm. Depth profiling by secondary-ion mass spectrometry revealed
      that the Si Nps were uniformly attached onto the TiO(2) films. The number of
      Ru(II) dye molecules adsorbed onto a TiO(2) film that was treated with the Si
      COOH Nps was 42 % higher than that on the untreated TiO(2) film. As a result,
      DSSCs that incorporated the Si-COOH Nps exhibited higher short-circuit
      photocurrent density and an overall energy-conversion efficiency than the
      untreated DSSCs by 22 % and 27 %, respectively. This enhanced performance, mostly
      owing to the intramolecular charge-transfer to TiO(2) from the dye molecules that
      were anchored to the Si-COOH Nps, was confirmed by comparing the performance with
      two different Ru(II) -bipyridine dyes (N719 and N749).

PMID- 22461425
TI  - Mechanosensory neurons, cutaneous mechanoreceptors, and putative mechanoproteins.
AB  - The mammalian skin has developed sensory structures (mechanoreceptors) that are
      responsible for different modalities of mechanosensitivity like touch, vibration,
      and pressure sensation. These specialized sensory organs are anatomically and
      functionally connected to a special subset of sensory neurons called
      mechanosensory neurons, which electrophysiologically correspond with Abeta
      fibers. Although mechanosensory neurons and cutaneous mechanoreceptors are rather
      well known, the biology of the sense of touch still remains poorly understood.
      Basically, the process of mechanosensitivity requires the conversion of a
      mechanical stimulus into an electrical signal through the activation of ion
      channels that gate in response to mechanical stimuli. These ion channels belong
      primarily to the family of the degenerin/epithelium sodium channels, especially
      the subfamily acid-sensing ion channels, and to the family of transient receptor
      potential channels. This review compiles the current knowledge on the occurrence
      of putative mechanoproteins in mechanosensory neurons and mechanoreceptors, as
      well as the involvement of these proteins on the biology of touch. Furthermore,
      we include a section about what the knock-out mice for mechanoproteins are
      teaching us. Finally, the possibilities for mechanotransduction in
      mechanoreceptors, and the common involvement of the ion channels, extracellular
      membrane, and cytoskeleton, are revisited.

PMID- 22461426
TI  - Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic
      mechanotransduction.
AB  - The mechanical properties of the extracellular matrix have recently been shown to
      promote myofibroblast differentiation and lung fibrosis. Mechanisms by which
      matrix stiffness regulates myofibroblast differentiation are not fully
      understood. The goal of this study was to determine the intrinsic mechanisms of
      mechanotransduction in the regulation of matrix stiffness-induced myofibroblast
      differentiation. A well established polyacrylamide gel system with tunable
      substrate stiffness was used in this study. Megakaryoblastic leukemia factor-1
      (MKL1) nuclear translocation was imaged by confocal immunofluorescent microscopy.
      The binding of MKL1 to the alpha-smooth muscle actin (alpha-SMA) gene promoter
      was quantified by quantitative chromatin immunoprecipitation assay. Normal human
      lung fibroblasts responded to matrix stiffening with changes in actin dynamics
      that favor filamentous actin polymerization. Actin polymerization resulted in
      nuclear translocation of MKL1, a serum response factor coactivator that plays a
      central role in regulating the expression of fibrotic genes, including alpha-SMA,
      a marker for myofibroblast differentiation. Mouse lung fibroblasts deficient in
      Mkl1 did not respond to matrix stiffening with increased alpha-SMA expression,
      whereas ectopic expression of human MKL1 cDNA restored the ability of Mkl1 null
      lung fibroblasts to express alpha-SMA. Furthermore, matrix stiffening promoted
      production and activation of the small GTPase RhoA, increased Rho kinase (ROCK)
      activity, and enhanced fibroblast contractility. Inhibition of RhoA/ROCK
      abrogated stiff matrix-induced actin cytoskeletal reorganization, MKL1 nuclear
      translocation, and myofibroblast differentiation. This study indicates that actin
      cytoskeletal remodeling-mediated activation of MKL1 transduces mechanical stimuli
      from the extracellular matrix to a fibrogenic program that promotes myofibroblast
      differentiation, suggesting an intrinsic mechanotransduction mechanism.

PMID- 22461427
TI  - 4-Phenylbutyric acid treatment rescues trafficking and processing of a mutant
      surfactant protein-C.
AB  - Mutations in the SFTPC gene, encoding surfactant protein-C (SP-C), are associated
      with interstitial lung disease (ILD). Knowledge of the intracellular fate of
      mutant SP-C is essential in the design of therapies to correct
      trafficking/processing of the proprotein, and to prevent the formation of
      cytotoxic aggregates. We assessed the potential of a chemical chaperone to
      correct the trafficking and processing of three disease-associated mutant SP-C
      proteins. HEK293 cells were stably transfected with wild-type (SP-C(WT)) or
      mutant (SP-C(L188Q), SP-C(Deltaexon4), or SP-C(I73T)) SP-C, and cell lines with a
      similar expression of SP-C mRNA were identified. The effects of the chemical
      chaperone 4-phenylbutyric acid (PBA) and lysosomotropic drugs on intracellular
      trafficking to the endolysosomal pathway and the subsequent conversion of SP-C
      proprotein to mature peptide were assessed. Despite comparable SP-C mRNA
      expression, proprotein concentrations varied greatly: SP-C(I73T) was more
      abundant than SP-C(WT) and was localized to the cell surface, whereas SP
      C(Deltaexon4) was barely detectable. In contrast, SP-C(L188Q) and SP-C(WT)
      proprotein concentrations were comparable, and a small amount of SP-C(L188Q) was
      localized to the endolysosomal pathway. PBA treatment restored the trafficking
      and processing of SP-C(L188Q) to SP-C(WT) concentrations, but did not correct the
      mistrafficking of SP-C(I73T) or rescue SP-C(Deltaexon4). PBA treatment also
      promoted the aggregation of SP-C proproteins, including SP-C(L188Q). This study
      provides proof of the principle that a chemical chaperone can correct the
      mistrafficking and processing of a disease-associated mutant SP-C proprotein.

PMID- 22461428
TI  - Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway
      epithelium: involvement of TRPC5.
AB  - In rodent lungs, a major part of the myelinated vagal airway afferents
      selectively contacts pulmonary neuroepithelial bodies (NEBs). Because most
      myelinated vagal airway afferents concern physiologically characterized
      mechanoreceptors, the present study aimed at unraveling the potential involvement
      of NEB cells in transducing mechanosensory information from the airways to the
      central nervous system. Physiological studies were performed using confocal
      Ca(2+) imaging of airway epithelium in murine lung slices. Mechanical stimulation
      by short-term application of a mild hypoosmotic solution (230 mosmol) resulted in
      a selective, fast, reversible, and reproducible Ca(2+) rise in NEB cells. Other
      airway epithelial cells could only be activated using more severe hypoosmotic
      stimuli (< 200 mosmol). NEB cells selectively expressed the Ca(2+)-permeable osmo
      and mechanosensitive transient receptor potential canonical channel 5 (TRPC5) in
      their apical membranes, whereas immunoreactivity for TRP vanilloid-4 and TRP
      melastatin-3 was abundant in virtually all other airway epithelial cells.
      Hypoosmotic activation of NEB cells was prevented by GsMTx-4, an inhibitor of
      mechanosensitive ion channels, and by SKF96365, an inhibitor of TRPC channels.
      Short application of gadolinium, reported to activate TRPC5 channels, evoked a
      transient Ca(2+) rise in NEB cells. Osmomechanical activation of NEB cells gave
      rise to a typical delayed activation of Clara-like cells due to the release of
      ATP from NEB cells. Because ATP may activate the NEB-associated P2X(2/3) ATP
      receptor expressing myelinated vagal afferents, the current observations strongly
      suggest that pulmonary NEB cells are fully equipped to initiate mechanosensory
      signal transduction to the central nervous system via a purinergic signaling
      pathway.

PMID- 22461430
TI  - Genetic ablation of the fpr1 gene confers protection from smoking-induced lung
      emphysema in mice.
AB  - Cigarette smoke (CS) is the main causative factor of chronic obstructive
      pulmonary disease (COPD). Current research supports the concept that airway
      inflammation is central to the development and progression of the disease.
      Studies have demonstrated that neutrophils are increased in COPD lungs and that
      neutrophil-associated products correlate with the development and severity of
      COPD. The peptide FMLP is an active component of CS. FMLP interacts on the
      neutrophil and macrophage membranes with a high-affinity receptor subtype (FPR1)
      and with a low-affinity subtype FPRL1, promoting a chemotactic response,
      superoxide anion production, and degranulation. Bacterial colonization of the
      lower respiratory tract and lung cell damage may represent further sources of
      formyl peptides in patients with COPD. We investigated the role of FPR in a mouse
      model on lung inflammation and emphysema induced by CS. Here, we report the novel
      observation that genetic ablation of the FPR1 gene (Fpr1) confers protection from
      smoking-induced lung emphysema in mice. Compared with wild-type mice, Fpr1
      knockout mice displayed marked decreases in the lung migration of neutrophils and
      macrophages after CS exposure. Upon transgenic approach, the changes in cell
      numbers were accompanied by marked modulation of the expression of genes
      implicated in the inflammatory response. Administration of the FPR1 antagonist
      cyclosporine H to wild-type mice attenuated the acute inflammatory response
      evoked by CS. These findings may have clinical significance because current
      smokers and subjects with emphysema showed increased FPR expression in
      bronchoalveolar fluids and on peripheral neutrophils. Modulating the FPR1 signal
      should be explored as a potential new therapy.

PMID- 22461429
TI  - Induction of a mesenchymal expression program in lung epithelial cells by
      wingless protein (Wnt)/beta-catenin requires the presence of c-Jun N-terminal
      kinase-1 (JNK1).
AB  - Recent studies suggest the importance of the transition of airway epithelial
      cells (EMT) in pulmonary fibrosis, and also indicate a role for Wingless protein
      (Wnt)/beta-catenin signaling in idiopathic pulmonary fibrosis. We investigated
      the possible role of the Wnt signaling pathway in inducing EMT in lung epithelial
      cells, and sought to unravel the role of c-Jun-N-terminal-kinase-1 (JNK1). The
      exposure of C10 lung epithelial cells or primary mouse tracheal epithelial cells
      (MTECs) to Wnt3a resulted in increases in JNK phosphorylation and nuclear beta
      catenin content. Because the role of beta-catenin as a transcriptional
      coactivator is well established, we investigated T-cell factor/lymphocyte
      enhancement factor (TCF/LEF) transcriptional activity in C10 lung epithelial
      cells after the activation of Wnt. TCF/LEF transcriptional activity was enhanced
      after the activation of Wnt, and this increase in TCF/LEF transcriptional
      activity was diminished after the small interfering (si)RNA-mediated ablation of
      JNK. The activation of the Wnt pathway by Wnt3a, or the expression of either wild
      type or constitutively active beta-catenin (S37A), led to the activation of an
      EMT transcriptome, manifested by the increased mRNA expression of CArG box
      binding factor-A, fibroblast-specific protein (FSP)-1, alpha-smooth muscle actin
      (alpha-SMA), and vimentin, increases in the content of alpha-SMA and FSP1, and
      the concomitant loss of zona occludens-1. The siRNA-mediated ablation of beta
      catenin substantially decreased Wnt3a-induced EMT. The siRNA ablation of JNK1
      largely abolished Wnt3a, beta-catenin, and beta-catenin S37a-induced EMT. In
      MTECs lacking Jnk1, Wnt3a-induced increases in nuclear beta-catenin, EMT
      transcriptome, and the content of alpha-SMA or FSP1 were substantially
      diminished. These data show that the activation of the Wnt signaling pathway is
      capable of inducing an EMT program in lung epithelial cells through beta-catenin,
      and that this process is controlled by JNK1.

PMID- 22461431
TI  - CHRNA3/5, IREB2, and ADCY2 are associated with severe chronic obstructive
      pulmonary disease in Poland.
AB  - We examined the association between single-nucleotide polymorphisms (SNPs)
      previously associated with chronic obstructive pulmonary disease (COPD) and/or
      lung function with COPD and COPD-related phenotypes in a novel cohort of patients
      with severe to very severe COPD. We examined 315 cases of COPD and 330 Caucasian
      control smokers from Poland. We included three SNPs previously associated with
      COPD: rs7671167 (FAM13A), rs13180 (IREB2), and rs8034191 (CHRNA 3/5), and four
      SNPs associated with lung function in a genome-wide association study of general
      population samples: rs2070600 (AGER), rs11134242 (ADCY2), rs4316710 (THSD4), and
      rs17096090 (INTS12). We tested for associations with severe COPD and COPD-related
      phenotypes, including lung function, smoking behavior, and body mass index.
      Subjects with COPD were older (average age 62 versus 58 years, P < 0.01), with
      more pack-years of smoking (45 versus 33 pack-years, P < 0.01). CHRNA3/5 (odds
      ratio [OR], 1.89; 95% confidence interval [CI], 1.5-2.4; P = 7.4 * 10(-7)), IREB2
      (OR, 0.69; 95% CI, 0.5-0.9; P = 3.4 * 10(-3)), and ADCY2 (OR, 1.35; 95% CI, 1.1
      1.7; P = 0.01) demonstrated significant associations with COPD. FAM13A (OR, 0.8;
      95% CI, 0.7-1.0; P = 0.11) approached statistical significance. FAM13A and ADCY2
      also demonstrated a significant association with lung function. Thus, in severe
      to very severe COPD, we demonstrate a replication of association between two SNPs
      previously associated with COPD (CHRNA3/5 and IREB2), as well as an association
      with COPD of one locus initially associated with lung function (ADCY2).

PMID- 22461432
TI  - Spreading of chronic pain between body regions: prospective cohort study among
      health care workers.
AB  - OBJECTIVE: To estimate the prognostic value of pain in one body region on the
      risk for developing chronic pain in other body regions. METHODS: Prospective
      cohort study among 5052 Danish female health care workers responding to a
      baseline and follow-up questionnaire in 2005 and 2006, respectively. Using
      adjusted logistic regression analysis, the risk for developing chronic pain (>30
      days last year) at follow-up in the low back (among those without low back pain
      during the last year at baseline) when experiencing sub-chronic (1-30 days last
      year) or chronic pain in other body regions (i.e., the neck/shoulders and/or the
      knees at baseline) was modelled. Similar risks were modelled for developing
      chronic pain in the neck/shoulders and knees. RESULTS: Chronic pain in the
      neck/shoulders (OR 3.14; 95% CI 1.74-5.70) or knees (OR 2.57; 95% CI 1.28-5.16)
      at baseline increased the risk for developing chronic pain in the low back at
      follow-up. Likewise, chronic pain in the neck/shoulders (OR 2.39; 95% CI 1.36
      4.17) or low back (OR 1.82 95%; CI 1.07-3.09) at baseline increased the risk for
      developing chronic pain in the knees at follow-up. The risk for developing
      chronic neck/shoulder pain was not significantly increased when having pain in
      the low back or knees at baseline. CONCLUSION: Among health care workers, chronic
      musculoskeletal pain in one body region increases the risk for developing chronic
      pain in other pain-free body regions. Prevention of musculoskeletal disorders
      among health care workers should focus holistically on the musculoskeletal
      system.

PMID- 22461433
TI  - Toxicokinetic profile of N-(2-aminoethyl)ethanolamine in the female Wistar rat
      and distribution into the late gestation fetus and milk.
AB  - N-(2-aminoethyl)ethanolamine (AEEA) caused aneurysms of the great vessels in rats
      exposed in utero and during the first days post partum, exacerbated by postnatal
      treatment of the lactating dams (Moore et al., 2012). The purpose of this work
      was to examine the systemic availability of AEEA during gestation and early
      lactation. The absorption of AEEA was determined following oral administration to
      nonpregnant and pregnant female Wistar rats. A single dose administered by gavage
      (0.5 or 50 mg/kg) on gestation day 18 was rapidly and extensively (>90%) absorbed
      from the gastrointestinal tract (absorption t(1/2)  = 0.1-0.2 hr). Elimination
      from the plasma followed a biphasic pattern, with a rapid elimination phase
      (t(1/2 alpha)  = 1.6-1.8 hr) followed by a slower phase (t(1/2 beta)  = 16.7-17.3
      hr). Following repeated gavage administration during gestation day 17 to 19, (14)
      C-AEEA-derived radioactivity readily partitioned into the fetus and was evenly
      distributed therein, but cleared approximately twofold slower from the fetal
      blood and tissues than the maternal blood and chorioallantoic placenta. When
      administered to lactating dams during lactation days 1 to 12, (14) C-AEEA-derived
      radioactivity preferentially partitioned into the milk reaching levels that were
      between 1.6- and 2.5-fold higher than the maternal blood. Although the
      concentration of AEEA equivalents in the maternal blood remained quite
      consistent, the concentration in the milk fell by almost 40% between lactation
      days 4 and 12, probably reflecting an increase in milk production over this same
      period. We confirm exposure of the offspring to AEEA both in utero and during
      lactation, but that AEEA does not appear to specifically concentrate in the great
      vessels.

PMID- 22461434
TI  - Squaramides as potent transmembrane anion transporters.

PMID- 22461435
TI  - Carbazolyl benzo[1,2-b:4,5-b']difuran: an ambipolar host material for full-color
      organic light-emitting diodes.
AB  - We have designed an ambipolar material, 3,7-bis[4-(N-carbazolyl)-phenyl]-2,6
      diphenylbenzo[1,2-b:4,5-b']difuran (CZBDF), and synthesized it by zinc-mediated
      double cyclization. Its physical properties clarified that CZBDF possesses a wide
      gap character, well-balanced and high hole and electron mobilities of larger than
      10(-3) cm(2) V(-1) s(-1), and a high thermal stability. Using CZBDF as a host
      material for heterojunction OLED devices, a full range of visible emission was
      obtained. Notably, CZBDF also enabled us to fabricate RGB-emitting homojunction
      OLEDs, with performances comparable or superior to the heterojunction devices
      composed of several materials.

PMID- 22461436
TI  - Validating the truth of propositions: behavioral and ERP indicators of truth
      evaluation processes.
AB  - We investigated processes of truth validation during reading. Participants
      responded to 'true' and 'false' probes after reading simple true or false
      sentences. Compatible sentence/probe combinations (true/'true', false/'false')
      facilitated responding compared with incompatible combinations (true/'false',
      false/'true'), indicating truth validation. Evidence for truth validation was
      obtained after inducing an evaluative mindset but not after inducing a non
      evaluative mindset, using additional intermixed tasks requiring true/false
      decisions or sentence comparisons, respectively. Event-related potentials
      revealed an increased late negativity (500-1000 ms after onset of the last word
      of sentences) for false compared with true sentences. Paralleling behavioral
      results, this electroencephalographic marker only obtained in the evaluative
      mindset condition. Further, mere semantic mismatches between subject and object
      of sentences led to an elevated N400 for both mindset conditions. Taken together,
      our findings suggest that truth validation is a conditionally automatic process
      that is dependent on the current task demands and resulting mindset, whereas the
      processing of word meaning and semantic relations between words proceeds in an
      unconditionally automatic fashion.

PMID- 22461437
TI  - Rat airway morphometry measured from in situ MRI-based geometric models.
AB  - Rodents have been widely used to study the environmental or therapeutic impact of
      inhaled particles. Knowledge of airway morphometry is essential in assessing
      geometric influence on aerosol deposition and in developing accurate lung models
      of aerosol transport. Previous morphometric studies of the rat lung performed ex
      situ provided high-resolution measurements (50-125 MUm). However, it is unclear
      how the overall geometry of these casts might have differed from the natural in
      situ appearance. In this study, four male Wistar rat (268 +/- 14 g) lungs were
      filled sequentially with perfluorocarbon and phosphate-buffered saline before
      being imaged in situ in a 7-T magnetic resonance (MR) scanner at a resolution of
      0.2 * 0.2 * 0.27 mm. Airway length, diameter, gravitational, bifurcation, and
      rotational angles were measured for the first four airway generations from 3D
      geometric models built from the MR images. Minor interanimal variability
      [expressed by the relative standard deviation RSD (=SD/mean)] was found for
      length (0.18 +/- 0.07), diameter (0.15 +/- 0.15), and gravitational angle (0.12
      +/- 0.06). One rat model was extended to 16 airway generations. Organization of
      the airways using a diameter-defined Strahler ordering method resulted in lower
      interorder variability than conventional generation-based grouping for both
      diameter (RSD = 0.12 vs. 0.42) and length (0.16 vs. 0.67). Gravitational and
      rotational angles averaged 82.9 +/- 37.9 degrees  and 53.6 +/- 24.1 degrees ,
      respectively. Finally, the major daughter branch bifurcated at a smaller angle
      (19.3 +/- 14.6 degrees ) than the minor branch (60.5 +/- 19.4 degrees ). These
      data represent the most comprehensive set of rodent in situ measurements to date
      and can be used readily in computational studies of lung function and aerosol
      exposure.

PMID- 22461438
TI  - Nonlinearity between action potential alternans and restitution, which both
      predict ventricular arrhythmic properties in Scn5a+/- and wild-type murine
      hearts.
AB  - Electrocardiographic QT- and T-wave alternans, presaging ventricular arrhythmia,
      reflects compromised adaptation of action potential (AP) duration (APD) to
      altered heart rate, classically attributed to incomplete Na(v)1.5 channel
      recovery prior to subsequent stimulation. The restitution hypothesis suggests a
      function whose slope directly relates to APD alternans magnitude, predicting a
      critical instability condition, potentially generating arrhythmia. The present
      experiments directly test for such correlations among arrhythmia, APD alternans
      and restitution. Mice haploinsufficient in the Scn5a, cardiac Na(+) channel gene
      (Scn5a(+/-)), previously used to replicate Brugada syndrome, were used, owing to
      their established arrhythmic properties increased by flecainide and decreased by
      quinidine, particularly in right ventricular (RV) epicardium. Monophasic APs,
      obtained during pacing with progressively decrementing cycle lengths, were
      systematically compared at RV and left ventricular epicardial and endocardial
      recording sites in Langendorff-perfused Scn5a(+/-) and wild-type hearts before
      and following flecainide (10 MUM) or quinidine (5 MUM) application. The extent of
      alternans was assessed using a novel algorithm. Scn5a(+/-) hearts showed greater
      frequencies of arrhythmic endpoints with increased incidences of ventricular
      tachycardia, diminished by quinidine, and earlier onsets of ventricular
      fibrillation, particularly following flecainide challenge. These features
      correlated directly with increased refractory periods, specifically in the RV,
      and abnormal restitution and alternans properties in the RV epicardium. The
      latter variables were related by a unique, continuous higher-order function,
      rather than a linear relationship with an unstable threshold. These findings
      demonstrate a specific relationship between alternans and restitution, as well as
      confirming their capacity to predict arrhythmia, but implicate mechanisms
      additional to the voltage feedback suggested in the restitution hypothesis.

PMID- 22461440
TI  - Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin
      proteasome systems in healthy mice.
AB  - Aerobic exercise training (AET) is an important mechanical stimulus that
      modulates skeletal muscle protein turnover, leading to structural rearrangement.
      Since the ubiquitin-proteasome system (UPS) and calpain system are major
      proteolytic pathways involved in protein turnover, we aimed to investigate the
      effects of intensity-controlled AET on the skeletal muscle UPS and calpain system
      and their association to training-induced structural adaptations. Long-lasting
      effects of AET were studied in C57BL/6J mice after 2 or 8 wk of AET. Plantaris
      cross-sectional area (CSA) and capillarization were assessed by myosin ATPase
      staining. mRNA and protein expression levels of main components of the UPS and
      calpain system were evaluated in plantaris by real-time PCR and Western
      immunoblotting, respectively. No proteolytic system activation was observed after
      2 wk of AET. Eight weeks of AET resulted in improved running capacity, plantaris
      capillarization, and CSA. Muscle RING finger-1 mRNA expression was increased in 8
      wk-trained mice. Accordingly, elevated 26S proteasome activity was observed in
      the 8-wk-trained group, without accumulation of ubiquitinated or carbonylated
      proteins. In addition, calpain abundance was increased by 8 wk of AET, whereas no
      difference was observed in its endogenous inhibitor calpastatin. Taken together,
      our findings indicate that skeletal muscle enhancements, as evidenced by
      increased running capacity, plantaris capillarization, and CSA, occurred in spite
      of the upregulated UPS and calpain system, suggesting that overactivation of
      skeletal muscle proteolytic systems is not restricted to atrophying states. Our
      data provide evidence for the contribution of the UPS and calpain system to
      metabolic turnover of myofibrillar proteins and skeletal muscle adaptations to
      AET.

PMID- 22461439
TI  - Skeletal muscle mitochondrial density, gene expression, and enzyme activities in
      human heart failure: minimal effects of the disease and resistance training.
AB  - Impaired skeletal muscle energetics could adversely affect physical and metabolic
      function in patients with heart failure (HF). The effect of HF on aspects of
      mitochondrial structure and function, independent of muscle disuse and other
      disease-related confounding factors, however, is unclear. Moreover, no study has
      evaluated whether resistance exercise training, a modality that increases
      functional capacity, might derive its benefits through modulation of
      mitochondrial structure and function. Thirteen HF patients and 14 age- and
      physical activity-matched controls were evaluated for skeletal muscle
      mitochondrial size/content, gene expression, and enzyme activity before and after
      an 18-wk resistance exercise-training program. At baseline, HF patients and
      controls had similar mitochondrial fractional areas, although HF patients had
      larger average mitochondrion size (P < 0.05) and a trend toward a reduced number
      of mitochondria (P <= 0.10). No differences in the expression of transcriptional
      regulators or cytochrome oxidase subunits or the activity of mitochondrial and
      cytosolic enzymes were noted. Relationships among transcriptional regulators
      suggested that networks controlling mitochondrial content and gene expression are
      intact. Resistance training increased (P < 0.01) mitochondrial transcription
      factor A expression in patients and controls, and this increase was related to
      improvements in muscle strength (P = 0.05). Training did not, however, alter
      mitochondrial size/content, enzyme activities, or expression of other
      transcriptional regulators. In conclusion, our results suggest that the HF
      syndrome has minimal effects on skeletal muscle mitochondrial biology when the
      confounding effects of muscle disuse and other disease-related factors are
      removed. Moreover, the beneficial effects of resistance training on physical
      function in HF patients and controls are likely not related to alterations in
      mitochondrial biology.

PMID- 22461441
TI  - Effects of dehydration on cerebrovascular control during standing after heavy
      resistance exercise.
AB  - We tested the hypothesis that dehydration exacerbates reductions of middle
      cerebral artery blood velocity (MCAv) and alters cerebrovascular control during
      standing after heavy resistance exercise. Ten males participated in two trials
      under 1) euhydration (EUH) and 2) dehydration (DEH; fluid restriction + 40 mg
      furosemide). We recorded finger photoplethysmographic arterial pressure and MCAv
      (transcranial Doppler) during 10 min of standing immediately after high-intensity
      leg press exercise. Symptoms (e.g., lightheadedness) were ranked by subjects
      during standing (1-5 scale). Low-frequency (LF) oscillations of mean arterial
      pressure (MAP) and mean MCAv were calculated as indicators of cerebrovascular
      control. DEH reduced plasma volume by 11% (P = 0.002; calculated from hemoglobin
      and hematocrit). During the first 30 s of standing after exercise, subjects
      reported greater symptoms during DEH vs. EUH (P = 0.05), but these were mild and
      resolved at 60 s. While MAP decreased similarly between conditions immediately
      after standing, MCAv decreased more with DEH than EUH (P = 0.02). With prolonged
      standing under DEH, mean MCAv remained below baseline (P <= 0.01), and below EUH
      values (P <= 0.05). LF oscillations of MAP were higher for DEH at baseline and
      during the entire 10 min of stand after exercise (P <= 0.057), while LF
      oscillations in mean MCAv were distinguishable only at baseline and 5 min
      following stand (P = 0.05). Our results suggest that mean MCAv falls below a
      "symptomatic threshold" in the acute phase of standing after exercise during DEH,
      although symptoms were mild and transient. During the prolonged phase of
      standing, increases in LF MAP and mean MCAv oscillations with DEH may help to
      maintain cerebral perfusion despite absolute MCAv remaining below the symptomatic
      threshold.

PMID- 22461442
TI  - Automated rodent in situ muscle contraction assay and myofiber organization
      analysis in sarcopenia animal models.
AB  - Age-related sarcopenia results in frailty and decreased mobility, which are
      associated with increased falls and long-term disability in the elderly. Given
      the global increase in lifespan, sarcopenia is a growing, unmet medical need.
      This report aims to systematically characterize muscle aging in preclinical
      models, which may facilitate the development of sarcopenia therapies. Naive rats
      and mice were subjected to noninvasive micro X-ray computed tomography (micro-CT)
      imaging, terminal in situ muscle function characterizations, and ATPase-based
      myofiber analysis. We developed a Definiens (Parsippany, NJ)-based algorithm to
      automate micro-CT image analysis, which facilitates longitudinal in vivo muscle
      mass analysis. We report development and characterization of translational in
      situ skeletal muscle performance assay systems in rat and mouse. The systems
      incorporate a custom-designed animal assay stage, resulting in enhanced force
      measurement precision, and LabVIEW (National Instruments, Austin, TX)-based
      algorithms to support automated data acquisition and data analysis. We used
      ATPase-staining techniques for myofibers to characterize fiber subtypes and
      distribution. Major parameters contributing to muscle performance were identified
      using data mining and integration, enabled by Labmatrix (BioFortis, Columbia,
      MD). These technologies enabled the systemic and accurate monitoring of muscle
      aging from a large number of animals. The data indicated that longitudinal muscle
      cross-sectional area measurement effectively monitors change of muscle mass and
      function during aging. Furthermore, the data showed that muscle performance
      during aging is also modulated by myofiber remodeling factors, such as changes in
      myofiber distribution patterns and changes in fiber shape, which affect myofiber
      interaction. This in vivo muscle assay platform has been applied to support
      identification and validation of novel targets for the treatment of sarcopenia.

PMID- 22461444
TI  - Re: Effects of leptin and obesity on the upper airway function by Polotsky et al.

PMID- 22461443
TI  - Four weeks of normobaric "live high-train low" do not alter muscular or systemic
      capacity for maintaining pH and K+ homeostasis during intense exercise.
AB  - It was investigated if athletes subjected to 4 wk of living in normobaric hypoxia
      (3,000 m; 16 h/day) while training at 800-1,300 m ["live high-train low" (LHTL)]
      increase muscular and systemic capacity for maintaining pH and K(+) homeostasis
      as well as intense exercise performance. The design was double-blind and placebo
      controlled. Mean power during 30-s all-out cycling was similar before and
      immediately after LHTL (650 +/- 31 vs. 628 +/- 32 W; n = 10) and placebo exposure
      (658 +/- 22 vs. 660 +/- 23 W; n = 6). Supporting the performance data, arterial
      plasma pH, lactate, and K(+) during submaximal and maximal exercise were also
      unaffected by the intervention in both groups. In addition, muscle buffer
      capacity (in mmol H(+).kg dry wt(-1).pH(-1)) was similar before and after in both
      the LHTL (140 +/- 12 vs. 140 +/- 16) and placebo group (145 +/- 2 vs. 140 +/- 3).
      The expression of sarcolemmal H(+) transporters (Na(+)/H(+) exchanger 1,
      monocarboxylate transporters 1 and 4), as well as expression of Na(+)-K(+) pump
      subunits-alpha(1), -alpha(2), and -beta(1) was also similar before and after the
      intervention. In conclusion, muscular and systemic capacity for maintaining pH
      and K(+) balance during exercise is similar before and after 4 wk of placebo
      controlled normobaric LHTL. In accordance, 30-s all-out sprint ability was
      similar before and after LHTL.

PMID- 22461445
TI  - Effects of eccentric exercise on toll-like receptor 4 signaling pathway in
      peripheral blood mononuclear cells.
AB  - This study aimed to investigate the response of the toll-like receptor 4 (TLR4)
      signaling pathway to an acute bout of eccentric exercise, and to assess whether
      eccentric training attenuated the effects induced by acute eccentric exercise.
      Twenty men (22.4 +/- 0.5 yr) were divided into a control group (CG, n = 8) and a
      training group (TG, n = 12). Both groups performed two acute eccentric bouts on a
      squat machine in a 9-wk interval. During this time, TG followed a 6-wk eccentric
      training program (3 session/wk; 3-5 sets of 10 repetitions with loads ranging
      between the 40 and 50% of maximal isometric voluntary contraction). CD14, TLR4,
      and TNF-alpha mRNA levels, and CD14, TLR4, myeloid differentiation factor 88,
      tumor necrosis factor receptor-associated factor 6, TIR-domain-containing adapter
      inducing interferon-beta, phospho-IkappaB kinases, phospho-IkappaB, phospho-ERK
      1/2, and TNF-alpha protein concentration were measured in peripheral blood
      mononuclear cells, before, immediately, and 2 h after each eccentric bout. The
      first acute eccentric bout triggered a proinflammatory response mediated by an
      upregulation of all of the factors measured within the TLR4 signaling pathway.
      Following the training period and after the second acute bout, CG showed a
      similar proinflammatory response than that seen after the first bout. However,
      the eccentric training intervention decreased significantly the protein
      concentration of all factors analyzed in TG compared with results obtained after
      the first bout. These results suggest that the TLR4-signaling pathway plays a
      critical role in the proinflammatory response seen after acute eccentric
      exercise. This response was attenuated after an eccentric training program
      through myeloid differentiation factor 88-dependent and -independent pathways.

PMID- 22461446
TI  - Cardiac torsion-strain relationships in fatigued primary biliary cirrhosis
      patients show accelerated aging: a pilot cross-sectional study.
AB  - The autoimmune liver disease primary biliary cirrhosis (PBC) is associated with
      life-altering fatigue in ~50% of patients. Previous work suggests that fatigued
      PBC subjects have evidence of autonomic dysfunction and may be at a higher risk
      of sudden cardiac death. The manifestation of this risk is not clear. This pilot
      study investigated whether alterations in cardiac torsion and strain could be
      detected in fatigued or nonfatigued early-stage PBC patients. We performed
      cardiac tissue tagging and anatomical cine-imaging in 13 early-stage PBC patients
      (including 7 with significant fatigue) and 10 control subjects to calculate
      cardiac torsion and strain throughout systole and diastole. From the cardiac
      tagging, we calculated the torsion-to-shortening ratio (TSR), a measure of
      subepicardial torsion exerting mechanical advantage over subendocardial
      shortening. Autonomic function testing was performed to evaluate baroreceptor
      effective index on standing. TSR was markedly increased in the fatigued PBC
      patients (0.70 +/- 0.13) compared with both controls (0.46 +/- 0.11, P = 0.002)
      and nonfatigued PBC patients (0.44 +/- 0.12, P = 0.003). Decreased baroreceptor
      effective index on standing strongly correlated with increased TSR within the
      whole PBC group (r = -0.71, P = 0.007). Fatigued PBC patients demonstrate a
      redistribution of myocardial strain characteristic of a reduced relative
      contribution to contraction from the subendocardium. This is analogous to the
      changes found in healthy aging for subjects ~16 yr older than the fatigued PBC
      patients. Hence the hearts of fatigued PBC patients may be subject to processes
      of accelerated aging.

PMID- 22461447
TI  - Pathways of Ca2+ entry and cytoskeletal damage following eccentric contractions
      in mouse skeletal muscle.
AB  - Muscles that are stretched during contraction (eccentric contractions) show
      deficits in force production and a variety of structural changes, including loss
      of antibody staining of cytoskeletal proteins. Extracellular Ca(2+) entry and
      activation of calpains have been proposed as mechanisms involved in these
      changes. The present study used isolated mouse extensor digitorum longus (EDL)
      muscles subjected to 10 eccentric contractions and monitored force production,
      immunostaining of cytoskeletal proteins, and resting stiffness. Possible pathways
      for Ca(2+) entry were tested with streptomycin (200 MUM), a blocker of stretch
      activated channels, and with muscles from mice deficient in the transient
      receptor potential canonical 1 gene (TRPC1 KO), a candidate gene for stretch
      activated channels. At 30 min after the eccentric contractions, the isometric
      force was decreased to 75 +/- 3% of initial control and this force loss was
      reduced by streptomycin but not in the TRPC1 KO. Desmin, titin, and dystrophin
      all showed patchy loss of immunostaining 30 min after the eccentric contractions,
      which was substantially reduced by streptomycin and in the TRPC1 KO muscles.
      Muscles showed a reduction of resting stiffness following eccentric contractions,
      and this reduction was eliminated by streptomycin and absent in the TRPC1 KO
      muscles. Calpain activation was determined by the appearance of a lower molecular
      weight autolysis product and MU-calpain was activated at 30 min, whereas the
      muscle-specific calpain-3 was not. To test whether the loss of stiffness was
      caused by titin cleavage, protein gels were used but no significant titin
      cleavage was detected. These results suggest that Ca(2+) entry following
      eccentric contractions is through a stretch-activated channel that is blocked by
      streptomycin and encoded or modulated by TRPC1.

PMID- 22461448
TI  - The Toxicology Education Summit: building the future of toxicology through
      education.
AB  - Toxicology and careers in toxicology, as well as many other scientific
      disciplines, are undergoing rapid and dramatic changes as new discoveries,
      technologies, and hazards advance at a blinding rate. There are new and ever
      increasing demands on toxicologists to keep pace with expanding global economies,
      highly fluid policy debates, and increasingly complex global threats to public
      health. These demands must be met with new paradigms for multidisciplinary,
      technologically complex, and collaborative approaches that require advanced and
      continuing education in toxicology and associated disciplines. This requires
      paradigm shifts in educational programs that support recruitment, development,
      and training of the modern toxicologist, as well as continued education and
      retraining of the midcareer professional to keep pace and sustain careers in
      industry, government, and academia. The Society of Toxicology convened the
      Toxicology Educational Summit to discuss the state of toxicology education and to
      strategically address educational needs and the sustained advancement of
      toxicology as a profession. The Summit focused on core issues of: building for
      the future of toxicology through educational programs; defining education and
      training needs; developing the "Total Toxicologist"; continued training and
      retraining toxicologists to sustain their careers; and, finally, supporting
      toxicology education and professional development. This report summarizes the
      outcomes of the Summit, presents examples of successful programs that advance
      toxicology education, and concludes with strategies that will insure the future
      of toxicology through advanced educational initiatives.

PMID- 22461449
TI  - Organic anion transporting polypeptide 1a1 null mice are sensitive to cholestatic
      liver injury.
AB  - Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed
      in livers of mice and is thought to transport bile acids (BAs) from blood into
      liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct
      ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against
      liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake
      of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male
      wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed
      higher serum alanine aminotransferase levels and more severe liver injury than WT
      mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice
      survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA
      concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not
      prevent BA accumulation in the liver. In addition, secondary BAs dramatically
      increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null
      BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting
      polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein
      [Mrp]-3, Mrp4, and organic solute transporter alpha/beta) transporters, as well
      as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of
      small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of
      farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated
      receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT
      BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of
      Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that
      Oatp1a1 plays a unique role in liver adaptive responses to obstructive
      cholestasis.

PMID- 22461450
TI  - Role of galectin-3 in acetaminophen-induced hepatotoxicity and inflammatory
      mediator production.
AB  - Galectin-3 (Gal-3) is a beta-galactoside-binding lectin implicated in the
      regulation of macrophage activation and inflammatory mediator production. In the
      present studies, we analyzed the role of Gal-3 in liver inflammation and injury
      induced by acetaminophen (APAP). Treatment of wild-type (WT) mice with APAP (300
      mg/kg, ip) resulted in centrilobular hepatic necrosis and increases in serum
      transaminases. This was associated with increased hepatic expression of Gal-3
      messenger RNA and protein. Immunohistochemical analysis showed that Gal-3 was
      predominantly expressed by mononuclear cells infiltrating into necrotic areas.
      APAP-induced hepatotoxicity was reduced in Gal-3-deficient mice. This was most
      pronounced at 48-72 h post-APAP and correlated with decreases in APAP-induced
      expression of 24p3, a marker of inflammation and oxidative stress. These effects
      were not due to alterations in APAP metabolism or hepatic glutathione levels. The
      proinflammatory proteins, inducible nitric oxide synthase (iNOS), interleukin
      (IL)-1beta, macrophage inflammatory protein (MIP)-2, matrix metalloproteinase
      (MMP)-9, and MIP-3alpha, as well as the Gal-3 receptor (CD98), were upregulated
      in livers of WT mice after APAP intoxication. Loss of Gal-3 resulted in a
      significant reduction in expression of iNOS, MMP-9, MIP-3alpha, and CD98, with no
      effects on IL-1beta. Whereas APAP-induced increases in MIP-2 were augmented at 6
      h in Gal-3(-/-) mice when compared with WT mice, at 48 and 72 h, they were
      suppressed. Tumor necrosis factor receptor-1 (TNFR1) was also upregulated after
      APAP, a response dependent on Gal-3. Moreover, exaggerated APAP hepatotoxicity in
      mice lacking TNFR1 was associated with increased Gal-3 expression. These data
      demonstrate that Gal-3 is important in promoting inflammation and injury in the
      liver following APAP intoxication.

PMID- 22461451
TI  - BLTK1 murine Leydig cells: a novel steroidogenic model for evaluating the effects
      of reproductive and developmental toxicants.
AB  - Leydig cells are the primary site of androgen biosynthesis in males. Several
      environmental toxicants target steroidogenesis resulting in both developmental
      and reproductive effects including testicular dysgenesis syndrome. The aim of
      this study was to evaluate the effect of several structurally diverse endocrine
      disrupting compounds (EDCs) on steroidogenesis in a novel BLTK1 murine Leydig
      cell model. We demonstrate that BLTK1 cells possess a fully functional
      steroidogenic pathway that produces low basal levels of testosterone (T) and
      express all the necessary steroidogenic enzymes including Star, Cyp11a1, Cyp17a1,
      Hsd3b1, Hsd17b3, and Srd5a1. Recombinant human chorionic gonadotropin (rhCG) and
      forskolin (FSK) elicited concentration- and time-dependent induction of 3',5'
      cyclic adenosine monophosphate, progesterone (P), and T, as well as the
      differential expression of Star, Hsd3b6, Hsd17b3, and Srd5a1 messenger RNA
      levels. The evaluation of several structurally diverse male reproductive
      toxicants including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), atrazine,
      prochloraz, triclosan, monoethylhexyl phthalate (MEHP), glyphosate, and RDX in
      BLTK1 cells suggests different modes of action perturb steroidogenesis. For
      example, prochloraz and triclosan antifungals reduced rhCG induction of T,
      consistent with published in vivo data but did not alter basal T levels. In
      contrast, atrazine and MEHP elicited modest induction of basal T but antagonized
      rhCG-mediated induction of T levels, whereas TCDD, glyphosate, and RDX had no
      effect on basal or rhCG induction of T in BLTK1 cells. These results suggest that
      BLTK1 cells maintain rhCG-inducible steroidogenesis and are a viable in vitro
      Leydig cell model to evaluate the effects of EDCs on steroidogenesis. This model
      can also be used to elucidate the different mechanisms underlying toxicant
      mediated disruption of steroidogenesis.

PMID- 22461452
TI  - A novel mode-of-action mediated by the fetal muscle nicotinic acetylcholine
      receptor resulting in developmental toxicity in rats.
AB  - Sulfoxaflor (X11422208), a novel agricultural molecule, induced fetal effects
      (forelimb flexure, hindlimb rotation, and bent clavicle) and neonatal death in
      rats at high doses (>= 400 ppm in diet); however, no such effects occurred in
      rabbit dietary studies despite achieving similar maternal and fetal plasma
      exposure levels. Mode-of-action (MoA) studies were conducted to test the
      hypothesis that the effects in rats had a single MoA induced by sulfoxaflor
      agonism on the fetal rat muscle nicotinic acetylcholine receptor (nAChR). The
      studies included cross-fostering and critical windows of exposure studies in
      rats, fetal ((alpha1)(2)beta1gammadelta) and adult ((alpha1)(2)beta1deltaepsilon)
      rat and human muscle nAChR in vitro agonism experiments, and neonatal rat phrenic
      nerve-hemidiaphragm contracture studies. The weight of evidence from these
      studies supported a novel MoA where sulfoxaflor is an agonist to the fetal, but
      not adult, rat muscle nAChR and that prolonged agonism on this receptor in
      fetal/neonatal rats causes sustained striated muscle contracture resulting in
      concomitant reduction in muscle responsiveness to physiological nerve
      stimulation. Fetal effects were inducible with as little as 1 day of exposure at
      the end of gestation, but were rapidly reversible after birth, consistent with a
      pharmacological MoA. With respect to human relevance, sulfoxaflor was shown to
      have no agonism on human fetal or adult muscle nAChRs. Taken together, the data
      support the hypothesis that the developmental effects of sulfoxaflor in rats are
      mediated via sustained agonism on the fetal muscle nAChR during late fetal
      development and are considered not relevant to humans.

PMID- 22461453
TI  - Hepatic and pulmonary toxicogenomic profiles in mice intratracheally instilled
      with carbon black nanoparticles reveal pulmonary inflammation, acute phase
      response, and alterations in lipid homeostasis.
AB  - Global pulmonary and hepatic messenger RNA profiles in adult female C57BL/6 mice
      intratracheally instilled with carbon black nanoparticles (NPs) (Printex 90) were
      analyzed to identify biological perturbations underlying systemic responses to NP
      exposure. Tissue gene expression changes were profiled 1, 3, and 28 days
      following exposure to 0.018, 0.054, and 0.162 mg Printex 90 alongside controls.
      Pulmonary response was marked by increased expression of inflammatory markers and
      acute phase response (APR) genes that persisted to day 28 at the highest exposure
      dose. Genes in the 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase
      pathway were increased, and those involved in cholesterol efflux were decreased
      at least at the highest dose on days 1 and 3. Hepatic responses mainly consisted
      of the HMG-CoA reductase pathway on days 1 (high dose) and 28 (all doses).
      Protein analysis in tissues and plasma of 0.162 mg Printex 90-exposed mice
      relative to control revealed an increase in plasma serum amyloid A on days 1 and
      28 (p < 0.05), decreases in plasma high-density lipoprotein on days 3 and 28, an
      increase in plasma low-density lipoprotein on day 28 (p < 0.05), and marginal
      increases in total hepatic cholesterol on day 28 (p = 0.06). The observed changes
      are linked to APR. Although further research is needed to establish links between
      observations and the onset and progression of systemic disorders, the present
      study demonstrates the ability of NPs to induce systemic effects.

PMID- 22461454
TI  - Chromosome observation by scanning electron microscopy using ionic liquid.
AB  - Electron microscopy has been used to visualize chromosome since it has high
      resolution and magnification. However, biological samples need to be dehydrated
      and coated with metal or carbon before observation. Ionic liquid is a class of
      ionic solvent that possesses advantageous properties of current interest in a
      variety of interdisciplinary areas of science. By using ionic liquid, biological
      samples need not be dehydrated or metal-coated, because ionic liquid behaves as
      the electronically conducting material for electron microscopy. The authors have
      investigated chromosome using ionic liquid in conjunction with electron
      microscopy and evaluated the factors that affect chromosome visualization.
      Experimental conditions used in the previous studies were further optimized. As a
      result, prewarmed, well-mixed, and low concentration (0.5~1.0%) ionic liquid
      provides well-contrasted images, especially when the more hydrophilic and the
      higher purity ionic liquid is used. Image contrast and resolution are enhanced by
      the combination of ionic liquid and platinum blue staining, the use of an indium
      tin oxide membrane, osmium tetroxide-coated coverslip, or aluminum foil as
      substrate, and the adjustment of electron acceleration voltage. The authors
      conclude that the ionic-liquid method is useful for the visualization of
      chromosome by scanning electron microscopy without dehydration or metal coating.

PMID- 22461455
TI  - Emotion-related regulatory difficulties contribute to negative psychological
      outcomes in active-duty Iraq war soldiers with and without posttraumatic stress
      disorder.
AB  - Data suggest military personnel involved in U.S. military initiatives in Iraq and
      Afghanistan are returning from deployment with elevated rates of mental health
      diagnoses, including posttraumatic stress disorder (PTSD). The aim of this study
      was to examine difficulties with emotion regulation as a potential contributory
      mechanism by which soldiers have poorer psychological outcomes, such as
      depression, dissociation, alcohol abuse, and interpersonal difficulties.
      Participants were 44 active-duty male service members who comprised three groups,
      including those deployed with and without diagnosed PTSD and those prior to
      deployment. Participants in the PTSD group scored significantly higher on
      measures of self-reported depression, trauma-related dissociation, alcohol
      misuse, and social adjustment difficulties than did comparison groups.
      Importantly, difficulties with emotion regulation were found to partially mediate
      the relationship between PTSD and depression, poor social adjustment, and trauma
      related depersonalization but not alcohol misuse. Emotion-regulation difficulties
      are important to consider in the relationship between PTSD and additional
      psychological outcomes in recently deployed personnel. Implications for treatment
      are briefly discussed.

PMID- 22461456
TI  - Analysis of skeletal dysplasias in the Utah population.
AB  - The Utah Birth Defect Network (UBDN) collects population-based data for Utah on
      births from all resident women. The prevalence of skeletal dysplasias and
      epidemiologic characteristics/outcomes were evaluated. Cases categorized as a
      skeletal dysplasia from all live births, stillbirths, and pregnancy terminations
      (TAB) between 1999 and 2008 were reviewed by three clinical geneticists. After
      case review, 153 were included for analysis (88% live births, 3% stillborn, 9%
      TAB), and categorized by groupings defined by molecular, biochemical, and/or
      radiographic criteria as outlined in the 2010 Nosology and Classification of
      Genetic Skeletal Disorders. The overall prevalence for skeletal dysplasias was
      3.0 per 10,000 births, and 20.0 per 10,000 stillbirths. The most common
      diagnostic groups were osteogenesis imperfecta (OI; n = 40; 0.79 per 10,000),
      thanatophoric dysplasia (n = 22; 0.43 per 10,000), achondroplasia (n = 18; 0.35
      per 10,000), and cleidocranial dysplasia (n = 6; 0.12 per 10,000). The most
      common groups based on the 2010 Nosology and Classification of Genetic Skeletal
      Disorders were the FGFR3 chondrodysplasia group (n = 41; 0.81 per 10,000), the
      OI/decreased bone density group (n = 40; 0.79 per 10,000), and the type 2
      collagen group (n = 10; 0.2 per 10,000). Median age of postnatal diagnosis was 30
      days (range 1-2,162). Of those deceased, 88% were prenatally suspected; of those
      alive 29% prenatally suspected. Median age of death for live born individuals was
      1 day (range 1-1,450 days). Previously reported prevalence rates vary, but our
      data provide a population-based approach not limited to the perinatal/neonatal
      period. Understanding the range for survival within each group/diagnosis is
      beneficial for health care providers when counseling families.

PMID- 22461457
TI  - Molecular profiling of pancreatic neuroendocrine tumors in sporadic and Von
      Hippel-Lindau patients.
AB  - PURPOSE: Von Hippel-Lindau (VHL) disease is an inherited syndrome caused by
      germline mutations in the VHL tumor suppressor gene, predisposing to a variety of
      neoplasms including pancreatic neuroendocrine tumors (PanNET). In VHL disease,
      PanNET probably progress according to a specific pathway of carcinogenesis. Our
      aim was to characterize by molecular quantitative analysis a panel of molecules
      implicated in the VHL pathway and in tumor progression in the PanNET of patients
      with VHL. EXPERIMENTAL DESIGN: The expression of 52 genes was studied by
      quantitative reverse transcriptase PCR in 18 patients with VHL operated on for
      PanNET and compared with 16 non-VHL PanNET. The VHL and non-VHL tumors were
      matched according to their size and cell proliferation. For some genes, we looked
      for differences in the protein expression in VHL PanNET (n = 31), microadenomas
      (n = 22), and non-VHL PanNET (n = 16), included in tissue microarray blocks.
      RESULTS: Nineteen (36%) genes were significantly upregulated and three (6%)
      downregulated in VHL PanNET. The upregulated genes were related to (i) hypoxia
      inducible factor (HIF) molecules (CA9, HIF2A, and GLUT1), (ii) angiogenesis
      (CDH5, VEGFR1, EDNRA, ANGPT2, CD34, VEGFR2, VEGFA, and ANGPT1), (iii) the
      processes of epithelial-mesenchymal transition (VIM) and/or metastasis (LAMA4 and
      CXCR4), (iv) growth factors and receptors (PDGFB, IRS1, and ERBB1), or (v) cell
      cycle (CCND1 and CDKN2A). The downregulated genes were related to (i) EMT (OCLN)
      and (ii) signaling pathways (RPS6KB1 and GADD45B). CONCLUSION: This study shows
      that the progression of PanNET in patients with VHL tumors follows a specific
      pathway and supports that targeting molecules specifically involved may be of
      therapeutic importance.

PMID- 22461459
TI  - Monomeric linear diaminocarbene complexes of gold(I) show merit in
      enantioselective catalysis.

PMID- 22461458
TI  - New strategies in squamous cell carcinoma of the lung: identification of tumor
      drivers to personalize therapy.
AB  - Treatment for non-small cell lung cancer has been improving, with personalized
      treatment increasingly becoming a reality in the clinic. Unfortunately, these
      advances have largely been confined to the treatment of adenocarcinomas.
      Treatment options for squamous cell carcinoma (SCC) of the lung have lagged
      behind, partly because of a lack of understanding of the oncogenes driving SCC.
      Cytotoxic chemotherapy continues to be the only treatment option for many of our
      patients, and no genetic tests are clinically useful for patients with SCC.
      Recent advances in basic science have identified mutations and alterations in
      protein expression frequently found in SCCs, and clinical trials are ongoing to
      target these changes.

PMID- 22461460
TI  - Direct-type aldol reactions of fluorenylidene-protected/activated glycine esters
      with aldehydes for the synthesis of beta-hydroxy-alpha-amino acid derivatives.

PMID- 22461461
TI  - Strength training for athletes: does it really help sports performance?
AB  - The use of strength training designed to increase underlying strength and power
      qualities in elite athletes in an attempt to improve athletic performance is
      commonplace. Although the extent to which strength and power are important to
      sports performance may vary depending on the activity, the associations between
      these qualities and performance have been well documented in the literature. The
      purpose of this review is to provide a brief overview of strength training
      research to determine if it really helps improve athletic performance. While
      there is a need for more research with elite athletes to investigate the
      relationship between strength training and athletic performance, there is
      sufficient evidence for strength training programs to continue to be an integral
      part of athletic preparation in team sports.

PMID- 22461462
TI  - Salivary cortisol, heart rate, and blood lactate responses during elite downhill
      mountain bike racing.
AB  - PURPOSE: This study aimed to quantify the intensity profile of elite downhill
      mountain bike races during competitions. METHODS: Seventeen male downhill racers
      (22 +/- 5 y; 185.1 +/- 5.3 cm; 68.0 +/- 3.9 kg; VO2peak: 59.4 +/- 4.1 mL.min.kg
      1) participated in the International German Downhill Championships in 2010. The
      racers' peak oxygen uptake and heart rate (HR) at 2 and 4 mmol.L-1 blood lactate
      (HR2 and HR4), were assessed during an incremental laboratory step test (100 W,
      increase 40 W every 5 min). During the races, the HR was recorded and pre- and
      postrace blood lactate concentrations as well as salivary cortisol levels were
      obtained. RESULTS: During the race, the absolute time spent in the "easy"
      intensity zone was 23.3 +/- 6.8 s, 24.2 +/- 12.8 s (HR2-HR4) in the "moderate"
      zone, and 151.6 +/- 18.3 s (>HR4) in the "hard" zone. Eighty percent of the
      entire race was accomplished at intensities >90% HRpeak. Blood lactate
      concentrations postrace were higher than those obtained after the qualification
      heat (8.0 +/- 2.5 mmol.L-1 vs 6.7 +/- 1.8 mmol.L-1, P < .01). Salivary levels of
      cortisol before the competition and the qualification heat were twice as high as
      at resting state (P < .01). CONCLUSIONS: This study shows that mountain bike
      downhill races are conducted at high heart rates and levels of blood lactate as
      well as increased concentration of salivary cortisol as marker for psycho
      physiological stress.

PMID- 22461463
TI  - Effects of two contrast training programs on jump performance in rugby union
      players during a competition phase.
AB  - PURPOSE: There is little literature comparing contrast training programs
      typically performed by team-sport athletes within a competitive phase. We
      compared the effects of two contrast training programs on a range of measures in
      high-level rugby union players during the competition season. METHODS: THE
      programs consisted of a higher volume-load (strength-power) or lower volume-load
      (speed-power) resistance training; each included a tapering of loading (higher
      force early in the week, higher velocity later in the week) and was performed
      twice a week for 4 wk. Eighteen players were assessed for peak power during a
      bodyweight countermovement jump (BWCMJ), bodyweight squat jump (BWSJ), 50 kg
      countermovement jump (50CMJ), 50 kg squat jump (50SJ), broad jump (BJ), and
      reactive strength index (RSI; jump height divided by contact time during a depth
      jump). Players were then randomized to either training group and were reassessed
      following the intervention. Inferences were based on uncertainty in outcomes
      relative to thresholds for standardized changes. RESULTS: There were small
      between-group differences in favor of strength-power training for mean changes in
      the 50CMJ (8%; 90% confidence limits, +/-8%), 50SJ (8%; +/-10%), and BJ (2%; +/
      3%). Differences between groups for BWCMJ, BWSJ, and reactive strength index were
      unclear. For most measures there were smaller individual differences in changes
      with strength-power training. CONCLUSION: Our findings suggest that high-level
      rugby union athletes should be exposed to higher volume-load contrast training
      which includes one heavy lifting session each week for larger and more uniform
      adaptation to occur in explosive power throughout a competitive phase of the
      season.

PMID- 22461464
TI  - Diagnostic yield in adults screened at the Marfan outpatient clinic using the
      1996 and 2010 Ghent nosologies.
AB  - Marfan syndrome (MFS) is diagnosed according to the Ghent nosology, which has
      recently been revised. In the Netherlands, evaluation for possible MFS is
      performed in specialized Marfan outpatient clinics. We investigated the
      diagnostic yield in our clinic and the impact of the 2010 nosology. All adult
      patients (n = 343) who visited our clinic between 1998 and 2008 were included. We
      analyzed their reasons for referral, characteristics, and established diagnoses.
      In addition, we applied the 2010 nosology to all patients and compared the
      outcomes to those obtained with the 1996 nosology. Diagnoses that were made using
      the 1996 and the 2010 Ghent nosology included MFS (44/343 vs. 47/343), familial
      thoracic aortic aneurysm and/or dissection (22/343 vs. 22/343 patients), Loeys
      Dietz syndrome (4/343 vs. 4/343 patients), and (familial) mitral valve prolapse
      (MVPS; 5/343 vs. 28/343 patients). In both nosologies, 77% of MFS patients had an
      FBN1 mutation. The 2010 nosology led to an increase in the number of diagnoses
      made: 4 additional cases of MFS were identified (one patient was "lost" who no
      longer fulfilled the criteria) and 23 additional cases of MVPS were diagnosed.
      The diagnostic yield of patients with aortic root dilatation was 65% using the
      1996 nosology and 70% using the 2010 nosology. The change in diagnoses did not
      lead to a difference in clinical follow-up. We conclude that the diagnostic yield
      of our specialized clinic was high, in particular in patients with aortic root
      dilatation. Further more the 2010 Ghent nosology led to a significant increase in
      the number of diagnoses made, mainly due to lowering of the diagnostic threshold
      for MVPS.

PMID- 22461466
TI  - Editorial: Molecular Endocrinology articles in the spotlight for April 2012.

PMID- 22461468
TI  - IRIS: the unfortunate rainbow of HIV.
AB  - In this issue of Blood, Mahnke and colleagues identify polyfunctional CD4(+) T
      cell responses directed against specific opportunistic pathogens in HIV-infected
      patients who develop immune reconstitution inflammatory syndrome (IRIS) after
      initiation of antiretroviral therapy (ART). This work provides a mechanistic
      advance to our understanding of IRIS pathogenesis.

PMID- 22461469
TI  - Longer FVIII: the 4th generation.
AB  - In this issue of Blood, Powell and colleagues present the first human data after
      the infusion of a new recombinant factor VIII (FVIII) product that when fused
      with the Fc fragment of IgG1 results in significantly prolonged half-life in the
      circulation.

PMID- 22461470
TI  - Gene therapy, an ongoing revolution.
AB  - In this issue of Blood, Buchlis and colleagues describe the long-term persistence
      (up to 10 years) of factor IX (FIX) expression in adeno-associated virus serotype
      2 (AAV-2)-injected muscles of a patient with hemophilia B.

PMID- 22461471
TI  - CLL and deletion 13q14: merely the miRs?
AB  - In this issue of Blood, Lia et al present a novel mouse model that recapitulates
      the pathogenic mechanisms of human CLL with deletion 13q14. Their striking
      finding is that the size of the deletion correlates with disease penetrance and
      aggressiveness.

PMID- 22461472
TI  - GM-CSFRalpha: the sex-chromosome link to t(8;21)(+) AML?
AB  - In this issue of Blood,Matsuura and colleagues provide evidence that loss of
      GMCSF signaling promotes leukemic progression in association with one of the most
      frequently observed cytogenetic abnormalities in AML, the t(8;21)(q22;q22) that
      generates the RUNX1-ETO fusion protein.

PMID- 22461473
TI  - Homocysteine and thrombosis: guilt by association?
AB  - The long-recognized connection between homocysteine and thrombosis is examined in
      this issue of Blood in a study conducted by Dayal and colleagues. The results
      challenge the proposed mechanisms by which disordered homocysteine metabolism
      triggers vascular disease.

PMID- 22461474
TI  - Long-term results of chemoimmunotherapy with low-dose fludarabine,
      cyclophosphamide and high-dose rituximab as initial treatment for patients with
      chronic lymphocytic leukemia.

PMID- 22461475
TI  - Exome sequencing reveals a pallidin mutation in a Hermansky-Pudlak-like primary
      immunodeficiency syndrome.

PMID- 22461477
TI  - An extremely bright heteroleptic bis(dipyrrinato)zinc(II) complex.

PMID- 22461476
TI  - Decreased hepcidin expression in murine beta-thalassemia is associated with
      suppression of Bmp/Smad signaling.

PMID- 22461479
TI  - Microscopes and beyond--advanced pathology.

PMID- 22461482
TI  - Night's end.

PMID- 22461483
TI  - Inhibitory interneurons, oxidative stress, and schizophrenia.
AB  - Translational studies are becoming more common in schizophrenia research. The
      past couple of decades witnessed the emergence of novel ideas regarding
      schizophrenia pathophysiology that originated from both human and animal studies.
      The findings that glutamate and gamma-aminobutyric acid transmission are affected
      in the disease led to the hypothesis of altered inhibitory neurotransmission as
      critical for cognitive deficits and to an exploration of novel therapeutic
      approaches aimed at restoring excitation-inhibition balance. Much is to be done
      yet to elucidate the ultimate mechanisms by which excitation and inhibition are
      affected in this disorder; a comprehensive translational effort is necessary to
      address what may cause altered GABA function, for example. Here, we present an
      overview of the excitation-inhibition imbalance hypothesis in schizophrenia and
      discuss ongoing efforts aimed at determining whether cortical inhibitory
      interneurons are affected by oxidative stress during development.

PMID- 22461485
TI  - Transcriptome analysis of the entomopathogenic fungus Beauveria bassiana grown on
      cuticular extracts of the coffee berry borer (Hypothenemus hampei).
AB  - The coffee berry borer (CBB; Hypothenemus hampei) is a major pest of coffee
      responsible for significant crop losses worldwide. The entomopathogenic fungus
      Beauveria bassiana represents a natural means of controlling this insect pest;
      however, little is known concerning the molecular determinants that contribute to
      the virulence of the fungus towards the CBB. In order to examine genes involved
      in insect virulence, two expressed sequence tag (EST) libraries, representing
      germinating conidia and growing hyphae/mycelia of B. bassiana cells grown on
      cuticular extracts of the CBB were constructed and analysed. In total, 4186 cDNA
      transcripts were obtained, which included 2141 from the cuticle-germinated
      conidia and 2045 from the cuticle-grown mycelium libraries, respectively. The
      average sequence length obtained was 470 bp and transcript assembly resulted in a
      set of 1271 and 1305 unique gene sequences for the conidial and mycelia
      libraries, respectively. Around 50 % of the sequences in each library could be
      annotated by gene ontology terms. An analysis of the two generated libraries as
      well as a previously reported EST library of B. bassiana grown on chitin was
      performed. Between the cuticle-germinated conidia and the cuticle-grown mycelia
      libraries, 322 unique gene sequences were shared, of which 90 % could be
      annotated, leaving 949 unique cuticle-germinated conidial genes and 983 unique
      growing hyphae/mycelia genes of which around 65 % were annotated. ESTs shared
      between the libraries indicated a basic response pattern for B. bassiana against
      H. hampei, which included genes implicated in pathogenicity. The expression
      profiles of four genes were evaluated with a cyclophilin, an alkaline-like serine
      protease and a mitogen-activated protein kinase (MAPK), showing elevated
      expression during initial phases of infection, i.e. conidia germinating on insect
      extracts. These data provide clues and gene candidates for further exploration
      concerning the biology and molecular mechanisms of entomopathogenicity by this
      fungus.

PMID- 22461484
TI  - Childhood adversities increase the risk of psychosis: a meta-analysis of patient
      control, prospective- and cross-sectional cohort studies.
AB  - Evidence suggests that adverse experiences in childhood are associated with
      psychosis. To examine the association between childhood adversity and trauma
      (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental
      death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web
      of Science were searched from January 1980 through November 2011. We included
      prospective cohort studies, large-scale cross-sectional studies investigating the
      association between childhood adversity and psychotic symptoms or illness, case
      control studies comparing the prevalence of adverse events between psychotic
      patients and controls using dichotomous or continuous measures, and case-control
      studies comparing the prevalence of psychotic symptoms between exposed and
      nonexposed subjects using dichotomous or continuous measures of adversity and
      psychosis. The analysis included 18 case-control studies (n = 2048 psychotic
      patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective
      studies (n = 41,803) and 8 population-based cross-sectional studies (n = 35,546).
      There were significant associations between adversity and psychosis across all
      research designs, with an overall effect of OR = 2.78 (95% CI = 2.34-3.31). The
      integration of the case-control studies indicated that patients with psychosis
      were 2.72 times more likely to have been exposed to childhood adversity than
      controls (95% CI = 1.90-3.88). The association between childhood adversity and
      psychosis was also significant in population-based cross-sectional studies (OR =
      2.99 [95% CI = 2.12-4.20]) as well as in prospective and quasi-prospective
      studies (OR = 2.75 [95% CI = 2.17-3.47]). The estimated population attributable
      risk was 33% (16%-47%). These findings indicate that childhood adversity is
      strongly associated with increased risk for psychosis.

PMID- 22461486
TI  - Influence of the ADP/ATP ratio, 2-oxoglutarate and divalent ions on Azospirillum
      brasilense PII protein signalling.
AB  - Proteins belonging to the P(II) family coordinate cellular nitrogen metabolism by
      direct interaction with a variety of enzymes, transcriptional regulators and
      transporters. The sensing function of P(II) relies on its ability to bind the
      nitrogen/carbon signalling molecule 2-oxoglutarate (2-OG). In Proteobacteria,
      P(II) is further subject to reversible uridylylation according to the
      intracellular levels of glutamine, which reflect the cellular nitrogen status. A
      number of P(II) proteins have been shown to bind ADP and ATP in a competitive
      manner, suggesting that P(II) might act as an energy sensor. Here, we analyse the
      influence of the ADP/ATP ratio, 2-OG levels and divalent metal ions on in vitro
      uridylylation of the Azospirillum brasilense P(II) proteins GlnB and GlnZ, and on
      interaction with their targets AmtB, DraG and DraT. The results support the
      notion that the cellular concentration of 2-OG is a key factor governing
      occupation of the GlnB and GlnZ nucleotide binding sites by ATP or ADP, with high
      2-OG levels favouring the occupation of P(II) by ATP. Both P(II) uridylylation
      and interaction with target proteins responded to the ADP/ATP ratio within the
      expected physiological range, supporting the concept that P(II) proteins might
      act as cellular energy sensors.

PMID- 22461487
TI  - A study on the presence of flagella in the order Rickettsiales: the case of
      'Candidatus Midichloria mitochondrii'.
AB  - According to Bergey's Manual of Systematic Bacteriology, the Rickettsiales are
      '...bacteria with typical gram-negative cell walls and no flagella'. The recently
      sequenced genome of 'Candidatus Midichloria mitochondrii', a divergent lineage
      within the order Rickettsiales capable of invading mitochondria in ixodid ticks,
      revealed the presence of 26 putative flagellar genes. Open questions in relation
      to this observation are whether these genes are expressed and whether they
      possess the domains expected for the flagellar function. Here we show that: (a)
      the putative flagellar proteins of 'Ca. M. mitochondrii' actually possess the
      conserved domains and structural features required for their function in a model
      bacterium; (b) the seven flagellar genes of 'Ca. M. mitochondrii' that have been
      tested are expressed at the RNA level; and (c) the putative flagellar cap gene of
      this bacterium (FliD) is expressed at the protein level, and can be stained
      within the bacterium and at its surface. Beside the specific questions that we
      have addressed that relate to the first evidence, to our knowledge, for a
      flagellar apparatus in a member of the order Rickettsiales, we present here novel
      tools (recombinant protein and antibodies) that will facilitate the study of 'Ca.
      M. mitochondrii'.

PMID- 22461488
TI  - A broadly applicable gene knockout system for the thermoacidophilic archaeon
      Sulfolobus islandicus based on simvastatin selection.
AB  - Sulfolobus species have been developed as excellent model organisms to address
      fundamental questions of archaeal biology. Interesting patterns of natural
      variation among Sulfolobus islandicus strains have been identified through genome
      sequencing. Experimentally testing hypotheses about the biological causes and
      consequences of this natural variation requires genetic tools that apply to a
      diversity of strains. Previously, a genetic transformation system for S.
      islandicus was reported, in which overexpression of the 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase gene on the shuttle vector pSSR
      allowed the selection of transformants resistant to high concentrations of the
      thermostable antibiotic simvastatin. Here, we developed a novel gene knockout
      system based on simvastatin resistance. With this system, we created via
      homologous recombination an in-frame, markerless deletion of the intact S.
      islandicus M.16.4 pyrEF genes encoding orotidine-5'-monophosphate
      pyrophosphorylase (OPRTase) and orotidine-5'-monophosphate decarboxylase
      (OMPdecase), and a disruption of the lacS gene encoding beta-galactosidase.
      Phenotypic analyses of the mutants revealed that the pyrEF deletion mutant lost
      the ability to synthesize uracil, and the lacS deletion mutants exhibited a white
      colour after X-Gal staining, demonstrating that the beta-galactosidase function
      was inactivated. Our data demonstrate efficient tools to generate gene knockouts
      in a broad range of wild-type Sulfolobus strains.

PMID- 22461489
TI  - Functional and expressional analyses of the anti-FlhD4C2 factor gene ydiV in
      Escherichia coli.
AB  - Although Escherichia coli and Salmonella enterica serovar Typhimurium have a
      similar flagellar regulatory system, the response of flagellar synthesis to
      nutrient conditions is quite different between the two: that is, in low-nutrient
      conditions, flagellar synthesis is inhibited in Salmonella and enhanced in E.
      coli. In Salmonella, this inhibition is mediated by an anti-FlhD(4)C(2) factor,
      YdiV, which is expressed in low-nutrient conditions and binds to FlhD(4)C(2) to
      inhibit the expression of the class 2 flagellar genes. The fliZ gene encodes a
      repressor of the ydiV gene, and thus is required for efficient flagellar gene
      expression in low-nutrient conditions in Salmonella. In this study, we showed
      that the E. coli ydiV gene encodes a protein which inhibits motility and
      flagellar production when expressed from a multicopy plasmid. We showed further
      that E. coli YdiV binds to FlhD(4)C(2) and inhibits its binding to the class 2
      flagellar promoter. These results indicate that E. coli YdiV can also act as an
      anti-FlhD(4)C(2) factor. However, although the ydiV gene was transcribed
      efficiently in E. coli cells, the intracellular level of the YdiV protein was
      extremely low due to its inefficient translation. Consistent with this, E. coli
      cells did not require FliZ for efficient motility development. This indicates
      that, unlike in Salmonella, the FliZ-YdiV regulatory system does not work in the
      nutritional control of flagellar gene expression in E. coli.

PMID- 22461490
TI  - DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration
      during immune responses.
AB  - To migrate efficiently through the interstitium, dendritic cells (DCs) constantly
      adapt their shape to the given structure of the extracellular matrix and follow
      the path of least resistance. It is known that this amoeboid migration of DCs
      requires Cdc42, yet the upstream regulators critical for localization and
      activation of Cdc42 remain to be determined. Mutations of DOCK8, a member of the
      atypical guanine nucleotide exchange factor family, causes combined
      immunodeficiency in humans. In the present study, we show that DOCK8 is a Cdc42
      specific guanine nucleotide exchange factor that is critical for interstitial DC
      migration. By generating the knockout mice, we found that in the absence of
      DOCK8, DCs failed to accumulate in the lymph node parenchyma for T-cell priming.
      Although DOCK8-deficient DCs migrated normally on 2-dimensional surfaces, DOCK8
      was required for DCs to crawl within 3-dimensional fibrillar networks and to
      transmigrate through the subcapsular sinus floor. This function of DOCK8 depended
      on the DHR-2 domain mediating Cdc42 activation. DOCK8 deficiency did not affect
      global Cdc42 activity. However, Cdc42 activation at the leading edge membrane was
      impaired in DOCK8-deficient DCs, resulting in a severe defect in amoeboid
      polarization and migration. Therefore, DOCK8 regulates interstitial DC migration
      by controlling Cdc42 activity spatially.

PMID- 22461491
TI  - Regulation of murine normal and stress-induced erythropoiesis by Desert Hedgehog.
AB  - The function of Hedgehog signaling in hematopoiesis is controversial, with
      different experimental systems giving opposing results. Here we examined the role
      of Desert Hedgehog (Dhh) in the regulation of murine erythropoiesis. Dhh is one
      of 3 mammalian Hedgehog family proteins. Dhh is essential for testis development
      and Schwann cell function. We show, by analysis of Dhh-deficient mice, that Dhh
      negatively regulates multiple stages of erythrocyte differentiation. In Dhh
      deficient bone marrow, the common myeloid progenitor (CMP) population was
      increased, but differentiation from CMP to granulocyte/macrophage progenitor was
      decreased, and the mature granulocyte population was decreased, compared with
      wild-type (WT). In contrast, differentiation from CMP to
      megakaryocyte/erythrocyte progenitor was increased, and the
      megakaryocyte/erythrocyte progenitor population was increased. In addition, we
      found that erythroblast populations were Dhh-responsive in vitro and ex vivo and
      that Dhh negatively regulated erythroblast differentiation. In Dhh-deficient
      spleen and bone marrow, BFU-Es and erythroblast populations were increased
      compared with WT. During recovery of hematopoiesis after irradiation, and under
      conditions of stress-induced erythropoiesis, erythrocyte differentiation was
      accelerated in both spleen and bone marrow of Dhh-deficient mice compared with
      WT.

PMID- 22461492
TI  - The tumor suppressor p15Ink4b regulates the differentiation and maturation of
      conventional dendritic cells.
AB  - The tumor suppressor p15Ink4b is frequently inactivated by methylation in acute
      myeloid leukemia and premalignant myeloid disorders. Dendritic cells (DCs) as
      potent APCs play critical regulatory roles in antileukemic immune responses. In
      the present study, we investigated whether p15Ink4b can function as modulator of
      DC development. The expression of p15Ink4b is induced strongly during
      differentiation and activation of DCs, and its loss resulted in significant
      quantitative and qualitative impairments of conventional DC (cDC) development.
      Accordingly, ex vivo-generated BM-derived DCs from p15Ink4b-knockout mice express
      significantly decreased levels of the antigen-presenting (MHC II) and
      costimulatory (CD80 and CD86) molecules and have impaired immunostimulatory
      functions, such as antigen uptake and T-cell stimulation. Reexpression of
      p15Ink4b in progenitors restored these defects, and confirmed a positive role for
      p15Ink4b during cDC differentiation and maturation. Furthermore, we have shown
      herein that p15Ink4b expression increases phosphorylation of Erk1/Erk2 kinases,
      which leads to an elevated activity of the PU.1 transcription factor. In
      conclusion, our results establish p15Ink4b as an important modulator of cDC
      development and implicate a novel function for this tumor suppressor in the
      regulation of adaptive immune responses.

PMID- 22461493
TI  - Signaling and cytoskeletal requirements in erythroblast enucleation.
AB  - To understand the role of cytoskeleton and membrane signaling molecules in
      erythroblast enucleation, we developed a novel analysis protocol of
      multiparameter high-speed cell imaging in flow. This protocol enabled us to
      observe F-actin and phosphorylated myosin regulatory light chain (pMRLC)
      assembled into a contractile actomyosin ring (CAR) between nascent reticulocyte
      and nucleus, in a population of enucleating erythroblasts. CAR formation and
      subsequent enucleation were not affected in murine erythroblasts with genetic
      deletion of Rac1 and Rac2 GTPases because of compensation by Rac3. Pharmacologic
      inhibition or genetic deletion of all Rac GTPases altered the distribution of F
      actin and pMRLC and inhibited enucleation. Erythroblasts treated with NSC23766,
      cytochalasin-D, colchicine, ML7, or filipin that inhibited Rac activity, actin or
      tubulin polymerization, MRLC phosphorylation, or lipid raft assembly,
      respectively, exhibited decreased enucleation efficiency, as quantified by flow
      cytometry. As assessed by high-speed flow-imaging analysis, colchicine inhibited
      erythroblast polarization, implicating microtubules during the preparatory stage
      of enucleation, whereas NSC23766 led to absence of lipid raft assembly in the
      reticulocyte-pyrenocyte border. In conclusion, enucleation is a multistep process
      that resembles cytokinesis, requiring establishment of cell polarity through
      microtubule function, followed by formation of a contractile actomyosin ring, and
      coalescence of lipid rafts between reticulocyte and pyrenocyte.

PMID- 22461495
TI  - MPs back guidance on assisted suicide in first Commons debate for 40 years.

PMID- 22461494
TI  - Meeting the challenge of hematologic malignancies in sub-Saharan Africa.
AB  - Cancer is a leading cause of death and disability in sub-Saharan Africa and will
      eclipse infectious diseases within the next several decades if current trends
      continue. Hematologic malignancies, including non-Hodgkin lymphoma, leukemia,
      Hodgkin lymphoma, and multiple myeloma, account for nearly 10% of the overall
      cancer burden in the region, and the incidence of non-Hodgkin lymphoma and
      Hodgkin lymphoma is rapidly increasing as a result of HIV. Despite an increasing
      burden, mechanisms for diagnosing, treating, and palliating malignant hematologic
      disorders are inadequate. In this review, we describe the scope of the problem,
      including the impact of endemic infections, such as HIV, Epstein-Barr virus,
      malaria, and Kaposi sarcoma-associated herpesvirus. We additionally describe
      current limitations in hematopathology, chemotherapy, radiotherapy, hematopoietic
      stem cell transplantation, and supportive care and palliation. We review
      contemporary treatment and outcomes of hematologic malignancies in the region and
      outline a clinical service and research agenda, which builds on recent global
      health successes combating HIV and other infectious diseases. Achieving similar
      progress against hematologic cancers in sub-Saharan Africa will require the
      sustained collaboration and advocacy of the entire global cancer community.

PMID- 22461496
TI  - Carbon isotope constraints on the deglacial CO2 rise from ice cores.
AB  - The stable carbon isotope ratio of atmospheric CO(2) (delta(13)C(atm)) is a key
      parameter in deciphering past carbon cycle changes. Here we present
      delta(13)C(atm) data for the past 24,000 years derived from three independent
      records from two Antarctic ice cores. We conclude that a pronounced 0.3 per mil
      decrease in delta(13)C(atm) during the early deglaciation can be best explained
      by upwelling of old, carbon-enriched waters in the Southern Ocean. Later in the
      deglaciation, regrowth of the terrestrial biosphere, changes in sea surface
      temperature, and ocean circulation governed the delta(13)C(atm) evolution. During
      the Last Glacial Maximum, delta(13)C(atm) and atmospheric CO(2) concentration
      were essentially constant, which suggests that the carbon cycle was in dynamic
      equilibrium and that the net transfer of carbon to the deep ocean had occurred
      before then.

PMID- 22461497
TI  - Astronomy. Complex protostellar chemistry.

PMID- 22461498
TI  - A common pesticide decreases foraging success and survival in honey bees.
AB  - Nonlethal exposure of honey bees to thiamethoxam (neonicotinoid systemic
      pesticide) causes high mortality due to homing failure at levels that could put a
      colony at risk of collapse. Simulated exposure events on free-ranging foragers
      labeled with a radio-frequency identification tag suggest that homing is impaired
      by thiamethoxam intoxication. These experiments offer new insights into the
      consequences of common neonicotinoid pesticides used worldwide.

PMID- 22461499
TI  - Climate change. The ice age carbon puzzle.

PMID- 22461500
TI  - Neonicotinoid pesticide reduces bumble bee colony growth and queen production.
AB  - Growing evidence for declines in bee populations has caused great concern because
      of the valuable ecosystem services they provide. Neonicotinoid insecticides have
      been implicated in these declines because they occur at trace levels in the
      nectar and pollen of crop plants. We exposed colonies of the bumble bee Bombus
      terrestris in the laboratory to field-realistic levels of the neonicotinoid
      imidacloprid, then allowed them to develop naturally under field conditions.
      Treated colonies had a significantly reduced growth rate and suffered an 85%
      reduction in production of new queens compared with control colonies. Given the
      scale of use of neonicotinoids, we suggest that they may be having a considerable
      negative impact on wild bumble bee populations across the developed world.

PMID- 22461503
TI  - Canadian trainees could be accused of "battery" for performing pelvic
      examinations under anaesthesia, say legal analysts.

PMID- 22461502
TI  - Organic synthesis via irradiation and warming of ice grains in the solar nebula.
AB  - Complex organic compounds, including many important to life on Earth, are
      commonly found in meteoritic and cometary samples, though their origins remain a
      mystery. We examined whether such molecules could be produced within the solar
      nebula by tracking the dynamical evolution of ice grains in the nebula and
      recording the environments to which they were exposed. We found that icy grains
      originating in the outer disk, where temperatures were less than 30 kelvin,
      experienced ultraviolet irradiation exposures and thermal warming similar to that
      which has been shown to produce complex organics in laboratory experiments. These
      results imply that organic compounds are natural by-products of protoplanetary
      disk evolution and should be important ingredients in the formation of all
      planetary systems, including our own.

PMID- 22461501
TI  - GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals.
AB  - Inflammasomes are sensory complexes that alert the immune system to the presence
      of infection or tissue damage. These complexes assemble NLR (nucleotide binding
      and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like
      receptor) proteins to activate caspase-1 cleavage and interleukin (IL)-1beta/IL
      18 secretion. Here, we identified a non-NLR/ALR human protein that stimulates
      inflammasome assembly: guanylate binding protein 5 (GBP5). GBP5 promoted
      selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not
      crystalline inflammasome priming agents. Generation of Gbp5(-/-) mice revealed
      pronounced caspase-1 and IL-1beta/IL-18 cleavage defects in vitro and impaired
      host defense and Nlrp3-dependent inflammatory responses in vivo. Thus, GBP5
      serves as a unique rheostat for NLRP3 inflammasome activation and extends our
      understanding of the inflammasome complex beyond its core machinery.

PMID- 22461504
TI  - Doctors should be able to help terminally patients to die, say Quebec MPs.

PMID- 22461505
TI  - Half of GPs on clinical commissioning groups have financial links with private
      providers.

PMID- 22461506
TI  - HER3 is required for HER2-induced preneoplastic changes to the breast epithelium
      and tumor formation.
AB  - Increasing evidence suggests that HER2-amplified breast cancer cells use
      HER3/ErbB3 to drive therapeutic resistance to HER2 inhibitors. However, the role
      of ErbB3 in the earliest events of breast epithelial transformation remains
      unknown. Using mouse mammary specific models of Cre-mediated ErbB3 ablation, we
      show that ErbB3 loss prevents the progressive transformation of HER2
      overexpressing mammary epithelium. Decreased proliferation and increased
      apoptosis were seen in MMTV-HER2 and MMTV-Neu mammary glands lacking ErbB3, thus
      inhibiting premalignant HER2-induced hyperplasia. Using a transgenic model in
      which HER2 and Cre are expressed from a single polycistronic transcript, we
      showed that palpable tumor penetrance decreased from 93.3% to 6.7% upon ErbB3
      ablation. Penetrance of ductal carcinomas in situ was also decreased. In
      addition, loss of ErbB3 impaired Akt and p44/42 phosphorylation in preneoplastic
      HER2-overexpressing mammary glands and in tumors, decreased growth of preexisting
      HER2-overexpressing tumors, and improved tumor response to the HER2 tyrosine
      kinase inhibitor lapatinib. These events were rescued by reexpression of ErbB3,
      but were only partially rescued by ErbB36F, an ErbB3 mutant harboring six
      tyrosine-to-phenylalanine mutations that block its interaction with phosphatidyl
      inositol 3-kinase. Taken together, our findings suggest that ErbB3 promotes HER2
      induced changes in the breast epithelium before, during, and after tumor
      formation. These results may have important translational implications for the
      treatment and prevention of HER2-amplified breast tumors through ErbB3
      inhibition.

PMID- 22461507
TI  - Activation of Ras/PI3K/ERK pathway induces c-Myc stabilization to upregulate
      argininosuccinate synthetase, leading to arginine deiminase resistance in
      melanoma cells.
AB  - Melanomas and other cancers that do not express argininosuccinate synthetase
      (AS), the rate-limiting enzyme for arginine biosynthesis, are sensitive to
      arginine depletion with pegylated arginine deiminase (ADI-PEG20). However, ADI
      resistance eventually develops in tumors because of AS upregulation. Although it
      has been shown that AS upregulation involves c-Myc, the underlying mechanisms
      remain unknown. Here we show that ADI-PEG20 activates Ras signaling and the
      effector extracellular signal-regulated kinase (ERK) and phosphoinositide 3
      kinase (PI3K)/AKT/GSK-3beta kinase cascades, resulting in phosphorylation and
      stabilization of c-Myc by attenuation of its ubiquitin-mediated protein
      degradation mechanism. Inhibition of the induced cell signaling pathways using
      PI3K/AKT inhibitors suppressed c-Myc induction and enhanced ADI-mediated cell
      killing. Notably, in an animal model of AS-negative melanoma, combination therapy
      using a PI3K inhibitor plus ADI-PEG20 yielded additive antitumor effects as
      compared with either agent alone. Taken together, our findings offer mechanistic
      insight into arginine deprivation metabolism and ADI resistance, and they
      illustrate how combining inhibitors of the Ras/ERK and PI3K/AKT signaling
      pathways may improve ADI-PEG20 anticancer responses.

PMID- 22461509
TI  - Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is
      active against lung adenocarcinoma.
AB  - Although oncolytic virotherapy is a promising anticancer therapy, antitumor
      efficacy is hampered by low tumor selectivity. To identify a potent and selective
      oncolytic virotherapy, we carried out large-scale two-step screening of 28
      enteroviral strains and found that coxsackievirus B3 (CVB3) possessed specific
      oncolytic activity against nine human non-small cell lung cancer (NSCLC) cell
      lines. CVB3-mediated cytotoxicity was positively correlated with the expression
      of the viral receptors, coxsackievirus and adenovirus receptor, and decay
      accelerating factor, on NSCLC cells. In vitro assays revealed that the CVB3
      induced apoptosis and phosphoinositide 3-kinase/Akt and mitogen-activated protein
      (MAP)/extracellular signal-regulated (ERK) kinase (MEK) survival signaling
      pathways, leading to cytotoxicity and regulation of CVB3 replication.
      Intratumoral injections of CVB3 elicited remarkable regression of preestablished
      NSCLC tumors in vivo. Furthermore, administrations of CVB3 into xenografts on the
      right flank resulted in significantly durable regression of uninjected xenografts
      on the left flank, where replication-competent CVB3 was detected. All treatments
      with CVB3 were well tolerated without treatment-related deaths. In addition,
      after CVB3 infection, NSCLC cells expressed abundant cell surface calreticulin
      and secreted ATP as well as translocated extranuclear high-mobility group box 1,
      which are required for immunogenic cell death. Moreover, intratumoral CVB3
      administration markedly recruited natural killer cells and granulocytes, both of
      which contributed to the antitumor effects as shown by depletion assays,
      macrophages, and mature dendritic cells into tumor tissues. Together, our
      findings suggest that CVB3 is a potent and well-tolerated oncolytic agent with
      immunostimulatory properties active against both localized and metastatic NSCLC.

PMID- 22461508
TI  - MIF produced by bone marrow-derived macrophages contributes to teratoma
      progression after embryonic stem cell transplantation.
AB  - Although stem cell therapy holds promise as a potential treatment in a number of
      diseases, the tumorigenicity of embryonic stem cells (ESC) and induced
      pluripotent stem cells remains a major obstacle. In vitro predifferentiation of
      ESCs can help prevent the risk of teratoma formation, yet proliferating neural
      progenitors can generate tumors, especially in the presence of immunosuppressive
      therapy. In this study, we investigated the effects of the microenvironment on
      stem cell growth and teratoma development using undifferentiated ESCs. Syngeneic
      ESC transplantation triggered an inflammatory response that involved the
      recruitment of bone marrow (BM)-derived macrophages. These macrophages
      differentiated into an M2 or angiogenic phenotype that expressed multiple
      angiogenic growth factors and proteinases, such as macrophage migration
      inhibitory factor (MIF), VEGF, and matrix metalloproteinase 9, creating a
      microenvironment that supported the initiation of teratoma development. Genetic
      deletion of MIF from the host but not from ESCs specifically reduced angiogenesis
      and teratoma growth, and MIF inhibition effectively reduced teratoma development
      after ESC transplantation. Together, our findings show that syngeneic ESC
      transplantation provokes an inflammatory response that involves the rapid
      recruitment and activation of BM-derived macrophages, which may be a crucial
      driving force in the initiation and progression of teratomas.

PMID- 22461510
TI  - Phosphoproteomics identifies driver tyrosine kinases in sarcoma cell lines and
      tumors.
AB  - Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine
      phosphorylation are poorly understood. To better understand the signaling
      pathways active in sarcoma, we examined global tyrosine phosphorylation in
      sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were
      used to purify tyrosine phosphorylated peptides, which were then identified by
      liquid chromatography and tandem mass spectrometry. The findings were validated
      with RNA interference, rescue, and small-molecule tyrosine kinase inhibitors. We
      identified 1,936 unique tyrosine phosphorylated peptides, corresponding to 844
      unique phosphotyrosine proteins. In sarcoma cells alone, peptides corresponding
      to 39 tyrosine kinases were found. Four of 10 cell lines showed dependence on
      tyrosine kinases for growth and/or survival, including platelet-derived growth
      factor receptor (PDGFR)alpha, MET, insulin receptor/insulin-like growth factor
      receptor signaling, and SRC family kinase signaling. Rhabdomyosarcoma samples
      showed overexpression of PDGFRalpha in 13% of examined cases, and sarcomas showed
      abundant tyrosine phosphorylation and expression of a number of tyrosine
      phosphorylated tyrosine kinases, including DDR2, EphB4, TYR2, AXL, SRC, LYN, and
      FAK. Together, our findings suggest that integrating global phosphoproteomics
      with functional analyses with kinase inhibitors can identify drivers of sarcoma
      growth and survival.

PMID- 22461512
TI  - Pleural effusion in a patient with multiple myeloma.

PMID- 22461513
TI  - Commentary.

PMID- 22461514
TI  - Commentary.

PMID- 22461511
TI  - Interleukin-17 promotes formation and growth of prostate adenocarcinoma in mouse
      models.
AB  - The contributions of interleukin (IL)-17 to cancer remain unclear and somewhat
      controversial. We took a genetic approach to explore its role in prostate cancers
      by interbreeding IL-17 receptor C (IL-17RC)-deficient mice with mice that are
      conditionally mutant for PTEN, one established preclinical model for prostate
      cancer. Mice that were IL-17RC-deficient (IL-17RC(-)) displayed prostates that
      were smaller than mice that maintained IL-17RC expression (IL-17RC(+)). In
      addition, IL-17RC(-) mice developed a reduced number of invasive prostate
      adenocarcinomas with lower rates of cellular proliferation and higher apoptosis
      than IL-17RC(+) mice. Moreover, the fibromuscular stroma surrounding prostatic
      glands was relatively thicker in IL-17RC(-) mice and was associated with
      decreased matrix metalloproteinase (Mmp)7 expression and increased Timp1, 2, and
      4 expression, whereas administration of recombinant mouse IL-17 induced prostatic
      expression of Mmp7. Taken together, our results suggested that IL-17 promotes the
      formation and growth of prostate adenocarcinoma, and that an IL-17-MMP7 signaling
      axis is required for the transition of prostatic intraepithelial neoplasia to
      frank adenocarcinoma.

PMID- 22461515
TI  - Discerning trends in multiplex immunoassay technology with potential for resource
      limited settings.
AB  - BACKGROUND: In the search for more powerful tools for diagnoses of endemic
      diseases in resource-limited settings, we have been analyzing technologies with
      potential applicability. Increasingly, the process focuses on readily accessible
      bodily fluids combined with increasingly powerful multiplex capabilities to
      unambiguously diagnose a condition without resorting to reliance on a
      sophisticated reference laboratory. Although these technological advances may
      well have important implications for the sensitive and specific detection of
      disease, to date their clinical utility has not been demonstrated, especially in
      resource-limited settings. Furthermore, many emerging technological developments
      are in fields of physics or engineering, which are not readily available to or
      intelligible to clinicians or clinical laboratory scientists. CONTENT: This
      review provides a look at technology trends that could have applicability to high
      sensitivity multiplexed immunoassays in resource-limited settings. Various
      technologies are explained and assessed according to potential for reaching
      relevant limits of cost, sensitivity, and multiplex capability. Frequently, such
      work is reported in technical journals not normally read by clinical scientists,
      and the authors make enthusiastic claims for the potential of their technology
      while ignoring potential pitfalls. Thus it is important to draw attention to
      technical hurdles that authors may not be publicizing. SUMMARY:
      Immunochromatographic assays, optical methods including those involving
      waveguides, electrochemical methods, magnetorestrictive methods, and field-effect
      transistor methods based on nanotubes, nanowires, and nanoribbons reveal
      possibilities as next-generation technologies.

PMID- 22461516
TI  - Yuk-Ming Dennis Lo.

PMID- 22461517
TI  - A discrepant urine specific gravity.

PMID- 22461519
TI  - Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in
      APCMin/+ mice.
AB  - Chronic inflammation is increasingly recognized as a major contributor of human
      colorectal cancer (CRC). While gut microbiota can trigger inflammation in the
      intestinal tract, the precise signaling pathways through which host cells respond
      to inflammatory bacterial stimulation are unclear. Here, we show that gut
      microbiota enhances intestinal tumor load in the APC(Min/+) mouse model of CRC.
      Furthermore, systemic anemia occurs coincident with rapid tumor growth,
      suggesting a role for intestinal barrier damage and erythropoiesis-stimulating
      mitogens. Short-term stimulation assays of murine colonic tumor cells reveal that
      lipopolysaccharide, a microbial cell wall component, can accelerate cell growth
      via a c-Jun/JNK activation pathway. Colonic tumors are also infiltrated by CD11b+
      myeloid cells expressing high levels of phospho-STAT3 (p-Tyr705). Our results
      implicate the role of gut microbiota, through triggering the c-Jun/JNK and STAT3
      signaling pathways in combination with anemia, in the acceleration of tumor
      growth in APC(Min/+) mice.

PMID- 22461520
TI  - EGF promotes neuroendocrine-like differentiation of prostate cancer cells in the
      presence of LY294002 through increased ErbB2 expression independent of the
      phosphatidylinositol 3-kinase-AKT pathway.
AB  - An increased neuroendocrine (NE) cell population in prostate cancer is associated
      with more aggressive disease and recurrence after androgen-deprivation therapy,
      although the mechanism responsible is unknown. In this study, we report that the
      treatment of LNCaP cells with epidermal growth factor (EGF) in the presence of
      LY294002, an inhibitor of the phosphoinositol 3'-kinase (PI3K)-AKT pathway,
      induced an increase of levels and activity of ErbB2. Under these conditions, we
      also observed cell survival and NE differentiation. When we treated with
      wortmannin, another PI3K inhibitor, or we knocked down PI3K or AKT isoforms in
      the presence of EGF, ErbB2 up-regulation was not observed, suggesting that the
      increase of ErbB2 induced by EGF plus LY294002 is not mediated by the PI3K-Akt
      pathway. Other targets of LY294002 were also discounted. We also show that ErbB2
      up-regulation is directly involved in neuroendocine differentiation but not in
      cell survival as ErbB2 levels increased in parallel with NE differentiation
      marker levels, whereas ErbB2 knockdown reduced them; other NE differentiation
      inducers also increased the ErbB2 levels and the immunohistochemical analysis of
      prostate cancer samples showed colocalization of ErbB2 and chromogranin A. We
      found that, in LNCaP cells, EGF in combination with LY294002 increased ErbB2
      levels by a PI3K/AKT-independent mechanism and that this increase was associated
      with the acquisition of a NE phenotype. These results suggest that is worth
      reconsidering ErbB2 as a drug target in prostate cancer and this should be kept
      in mind when designing new clinical schedules for the treatment of this disease.

PMID- 22461521
TI  - Stem cells of the human epidermis and their niche: composition and function in
      epidermal regeneration and carcinogenesis.
AB  - Skin, as the largest organ, has long been subject of excellent and pioneering
      studies on stem cells and their role in tissue regulation and tumor formation. In
      particular, intensive research on mouse skin, and here especially the hair
      follicle, has largely extended our knowledge. Surprisingly, human skin, although
      the most easily accessible tissue in man, is far less conceived with regard to
      its stem cells and their specific environment (the niche). In consequence, these
      features are as yet only insufficiently defined and it still has to be elucidated
      how insights in cutaneous stem cell biology gained in mice can be extrapolated to
      humans. In the last few years, human model systems such as humanized mice or in
      vitro organotypic cultures that support maintenance or reconstruction of human
      skin and long-term epidermal regeneration have been developed. These models allow
      lineage tracing experiments and can be modified by adopting genetically
      manipulated cell types. Accordingly, they represent proper tools for human stem
      cell research and will clearly help to improve our still incomplete
      understanding. Like normal skin, the non-melanoma skin cancers and their
      respective tumors have gained considerable interest in basic as well as in
      clinical research. Being the most frequent human tumors globally, basal cell
      carcinomas and cutaneous squamous cell carcinomas (SCCs) continue to increase in
      incidence and specifically SCCs predominate in immunosuppressed transplant
      recipients. This review intends to compile the present knowledge on keratinocyte
      stem cells and their niches in normal skin and skin carcinomas with a special
      focus on the human situation. In particular, the role of the microenvironment,
      the niche, is emphasized, promoting our view of the decisive importance of the
      niche as a key regulatory element for controlling position, fate and regenerative
      potential of the stem cell population both in healthy skin and in carcinomas.

PMID- 22461522
TI  - Folate deprivation enhances invasiveness of human colon cancer cells mediated by
      activation of sonic hedgehog signaling through promoter hypomethylation and cross
      action with transcription nuclear factor-kappa B pathway.
AB  - Low folate status is well recognized as one of the metabolic stressors for
      colorectal cancer carcinogenesis, but its role in colon cancer invasion remains
      unknown. Activation of the Sonic hedgehog (Shh) signal in interaction with the
      transcription nuclear factor-kappa B (NF-kappaB) pathway is crucial for cancer
      aggressiveness. The aims of this study were to investigate whether and how folate
      deprivation promotes invasion by colon cancer cells in relation to Shh signaling
      and NF-kappaB pathway activation. Cultivation of epithelial colon carcinoma
      derived cells (HCT116) in folate-deficient (FD) medium enhanced cellular
      migration and invasion, in correlation with epithelial-mesenchymal transition
      (EMT) associated with Snail expression and E-cadherin suppression, increased
      production of beta1 integrin and increased proteolysis by matrix
      metalloproteinase 2. Blockade of Shh signaling by cyclopamine (CYC) or of NF
      kappaB activation by BAY abolished FD-enhanced EMT and invasion by HCT116 cells.
      FD cells had 50-80% less intracellular folate, associated with aberrant
      hypomethylation of the Shh promoter, than control cells, and increased binding of
      nuclear NF-kappaB subunit p65 to the Shh promoter region, which coincided with
      increased Shh expression and protein production of Shh ligand; in addition, the
      FD-induced Shh signaling targeted Gli1 transcription activator as well as Ptch
      receptor. The FD-induced Shh induction and activated signaling were blocked by NF
      kappaB inhibitor BAY. Blockade of Shh signaling abrogated FD-promoted NF-kappaB
      activation measured by IkappaBalpha degradation and by target gene TNFalpha
      expression. Taken together, these findings demonstrate that folate deprivation
      enhanced invasiveness of colon cancer cells mediated by activation of Shh
      signaling through promoter hypomethylation and cross actions with the NF-kappaB
      pathway.

PMID- 22461523
TI  - Inhibition of AMPK signalling by doxorubicin: at the crossroads of the cardiac
      responses to energetic, oxidative, and genotoxic stress.
AB  - AIMS: Cardiotoxic side effects of anthracyclines, the most widely used anticancer
      drugs, are well documented, while mechanisms involved are not fully elucidated.
      The cellular energy sensor and regulator AMP-activated protein kinase (AMPK) was
      suggested as a putative mediator of cardiotoxicity of doxorubicin, the leading
      anthracycline drug, by our earlier work. Here, we study the interference of
      doxorubicin with AMPK signalling and potentially involved mechanisms. METHODS AND
      RESULTS: Effects of doxorubicin on cell signalling are studied in isolated
      Langendorff-perfused Wistar rat hearts and in hearts from doxorubicin-treated
      Wistar rats. In both models, doxorubicin induces energetic, oxidative, and
      genotoxic stress. Despite energy depletion and unaffected AMPK upstream
      signalling, doxorubicin does not activate the AMPK pathway and even reduces basal
      phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. In
      contrast, oxidative and genotoxic stress do activate pro-survival mitogen
      activated protein kinase (MAPK) and Akt pathways, the latter via DNA-dependent
      protein kinase activation triggered by DNA damage. Combined inhibition of AMPK
      and activation of Akt and MAPK lead to activation of growth-stimulating mammalian
      target of rapamycin (mTOR) signalling. CONCLUSION: Our results suggest that in
      the doxorubicin-challenged heart, a combined energetic, oxidative, and genotoxic
      stress elicits a specific, hierarchical response where AMPK is inhibited at least
      partially by the known negative cross-talk with Akt and MAPK pathways, largely
      triggered by DNA damage signalling. Although such signalling can be protective,
      e.g. by limiting apoptosis, it primarily induces a negative feedback that
      increases cellular energy deficits, and via activation of mTOR signalling, it
      also contributes to the pathological cardiac phenotype in chronic doxorubicin
      toxicity.

PMID- 22461524
TI  - Reducing the impact of myocardial ischaemia/reperfusion injury.

PMID- 22461525
TI  - Heparin-binding hemagglutinin induces IFN-gamma(+) IL-2(+) IL-17(+)
      multifunctional CD4(+) T cells during latent but not active tuberculosis disease.
AB  - The mycobacterial heparin-binding hemagglutinin (HBHA) protein induces a potent
      gamma interferon (IFN-gamma) response in latent tuberculosis (TB) infection and
      is a candidate vaccine and diagnostic antigen. We have assessed HBHA-specific
      intracellular IFN-gamma, interleukin-2 (IL-2), and IL-17 production by CD4(+) T
      cells in TB cases and household contacts (HHCs) as well as the level of secreted
      IFN-gamma in whole-blood culture supernatant. HHCs were further classified as
      tuberculin skin test (TST) positive or negative, and the group was also divided
      as HIV positive or negative. Our study revealed that HBHA induces multifunctional
      IFN-gamma-, IL-2-, and IL-17-coexpressing CD4(+) T cells in HHCs but not in
      active TB cases; however, IFN-gamma levels in culture supernatant did not differ
      between participant groups. Further studies are needed to completely understand
      how HBHA induces immune responses in different disease groups.

PMID- 22461526
TI  - A novel tuberculosis DNA vaccine in an HIV-1 p24 protein backbone confers
      protection against Mycobacterium tuberculosis and simultaneously elicits robust
      humoral and cellular responses to HIV-1.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major infectious
      disease worldwide. Moreover, latent M. tuberculosis infection is more likely to
      progress to active TB and eventually leads to death when HIV infection is
      involved. Thus, it is urgent to develop a novel TB vaccine with immunogenicity to
      both M. tuberculosis and HIV. In this study, four uncharacterized T cell epitopes
      from MPT64, Ag85A, Ag85B, and TB10.4 antigens of M. tuberculosis were predicted,
      and HIV-1-derived p24, an immunodominant protein that can induce protective
      responses to HIV-1, was used as an immunogenic backbone. M. tuberculosis epitopes
      were incorporated separately into the gene backbone of p24, forming a pP24-Mtb
      DNA vaccine. We demonstrated that pP24-Mtb immunization induced a strong M.
      tuberculosis-specific cellular response as evidenced by T cell proliferation,
      cytotoxicity, and elevated frequency of gamma interferon (IFN-gamma)-secreting T
      cells. Interestingly, a p24-specific cellular response and high levels of p24
      specific IgG were also induced by pP24-Mtb immunization. When the protective
      effect was assessed after mycobacterial challenge, pP24-Mtb vaccination
      significantly reduced tissue bacterial loads and profoundly attenuated the
      mycobacterial infection-related lung inflammation and injury. Our findings
      demonstrated that the pP24-Mtb tuberculosis vaccine confers effective protection
      against mycobacterial challenge with simultaneously elicited robust immune
      responses to HIV-1, which may provide clues for developing novel vaccines to
      prevent dual infections.

PMID- 22461527
TI  - Analysis of the bactericidal response to an experimental Neisseria meningitidis
      vesicle vaccine.
AB  - Rabbit immunogenicity studies on an experimental trivalent native outer membrane
      vesicle vaccine derived from three serogroup B strains were conducted to evaluate
      the effectiveness of this vaccine at inducing an antibody response with serum
      bactericidal activity against meningococcal strains of other serogroups in
      addition to serogroup B strains. The results showed that the vaccine was capable
      of inducing an effective broad-based bactericidal antibody response in rabbits
      against a small sample of Neisseria meningitidis strains of serogroups C, W135,
      and X and, to a lesser extent, serogroups A and Y. Analysis of antibody
      specificity using a bactericidal depletion assay revealed that antibodies to
      lipooligosaccharide (LOS), PorA, and NadA induced in rabbits by the experimental
      trivalent outer membrane vesicle vaccine were responsible for most of the
      bactericidal activity against strains of the other N. meningitidis serogroups. In
      the case of serogroup A N. meningitidis strains, the outer membrane antigen NadA
      was primarily responsible for protection. The outer membrane antigens fHbp and
      OpcA were also effective in removing some bactericidal activity from the sera.

PMID- 22461528
TI  - Immune responses and safety after dart or booster vaccination of bison with
      Brucella abortus strain RB51.
AB  - One alternative for management of brucellosis in Yellowstone National Park bison
      (Bison bison) is vaccination of calves and yearlings. Although Brucella abortus
      strain RB51 vaccination protects bison against experimental challenge, the effect
      of booster vaccinations was unknown. This study characterized immunologic
      responses after dart or booster vaccination of bison with Brucella abortus strain
      RB51. In two studies, 8- to 10-month-old female bison were inoculated with saline
      (n = 14), hand vaccinated with 1.1 * 10(10) to 2.0 * 10(10) CFU of RB51 (n = 21),
      or dart vaccinated with 1.8 * 10(10) CFU of RB51 (n = 7). A subgroup of hand
      vaccinates in study 1 was randomly selected for booster vaccination 15 months
      later with 2.2 * 10(10) CFU of RB51. Compared to single vaccinates, booster
      vaccinated bison had greater serologic responses to RB51. However, there was a
      trend for antigen-specific proliferative responses of peripheral blood
      mononuclear cells (PBMC) from booster vaccinates to be reduced compared to
      responses of PBMC from single vaccinates. PBMC from booster vaccinates tended to
      have greater gamma interferon (IFN-gamma) production than those from single
      vaccinates. In general, dart vaccination with RB51 induced immunologic responses
      similar to those of hand vaccination. All vaccinates (single hand, dart, or
      booster) demonstrated greater (P < 0.05) immunologic responses at various times
      after vaccination than nonvaccinated bison. Booster vaccination with RB51 in
      early gestation did not induce abortion or fetal infection. Our data suggest that
      booster vaccination does not induce strong anamnestic responses. However,
      phenotypic data on resistance to experimental challenge are required to fully
      assess the effect of booster vaccination on protective immunity.

PMID- 22461529
TI  - Added value of use of a purified protein derivative-based enzyme-linked
      immunosorbent spot assay for patients with Mycobacterium bovis BCG infection
      after intravesical BCG instillations.
AB  - In this case series, we describe four cases in which the use of gamma interferon
      release assays with purified protein derivative (PPD) as a stimulating antigen
      was able to demonstrate PPD-specific immune activation. This may help to improve
      the adequate diagnosis of (systemic) Mycobacterium bovis BCG infections after
      intravesical BCG instillations for bladder carcinoma.

PMID- 22461530
TI  - Immunogenicity of HIV virus-like particles in rhesus macaques by intranasal
      administration.
AB  - Female rhesus macaques were immunized with HIV virus-like particles (HIV-VLPs) or
      HIV DNA administered as sequential combinations of mucosal (intranasal) and
      systemic (intramuscular) routes, according to homologous or heterologous prime
      boost schedules. The results show that in rhesus macaques only the sequential
      intranasal and intramuscular administration of HIV-VLPs, and not the intranasal
      alone, is able to elicit humoral immune response at the systemic as well as the
      vaginal level.

PMID- 22461532
TI  - High-volume peritoneal dialysis in acute kidney injury: indications and
      limitations.
AB  - BACKGROUND AND OBJECTIVES: Peritoneal dialysis is still used for AKI in
      developing countries despite concerns about its limitations. The objective of
      this study was to explore the role of high-volume peritoneal dialysis in AKI
      patients in relation to metabolic and fluid control, outcome, and risk factors
      associated with death. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      prospective study was performed on 204 AKI patients who were assigned to high
      volume peritoneal dialysis (prescribed Kt/V=0.60/session) by flexible catheter
      and cycler; 150 patients (80.2%) were included in the final analysis. RESULTS:
      Mean age was 63.8+/-15.8 years, 70% of patients were in the intensive care unit,
      and sepsis was the main etiology of AKI (54.7%). BUN and creatinine levels
      stabilized after four sessions at around 50 and 4 mg/dl, respectively. Fluid
      removal and nitrogen balance increased progressively and stabilized around 1200
      ml and -1 g/d after four sessions, respectively. Weekly delivered Kt/V was 3.5+/
      0.68. Regarding AKI outcome, 23% of patients presented renal function recovery,
      6.6% of patients remained on dialysis after 30 days, and 57.3% of patients died.
      Age and sepsis were identified as risk factors for death. In urine output,
      increase of 1 g in nitrogen balance and increase of 500 ml in ultrafiltration
      after three sessions were identified as protective factors. CONCLUSIONS: High
      volume peritoneal dialysis is effective for a selected AKI patient group,
      allowing adequate metabolic and fluid control. Age, sepsis, and urine output as
      well as nitrogen balance and ultrafiltration after three high-volume peritoneal
      dialysis sessions were associated significantly with death.

PMID- 22461531
TI  - Collapsing glomerulopathy in 19 patients with systemic lupus erythematosus or
      lupus-like disease.
AB  - BACKGROUND AND OBJECTIVES: Collapsing glomerulopathy is a podocytopathy with
      segmental or global wrinkling and collapse of capillary walls and overlying
      epithelial cell proliferation. Idiopathic collapsing glomerulopathy is a distinct
      clinicopathologic entity with significant proteinuria, poor response to
      immunosuppressive therapy, and rapid progression to renal failure. Collapsing
      glomerulopathy is associated with viral infections, autoimmune disease, and
      drugs. This work presents the largest group of collapsing glomerulopathy in
      patients with SLE. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Clinicopathological features were retrospectively studied in 19 patients with SLE
      (16 patients) or SLE-like (3 patients) disease with collapsing glomerulopathy.
      RESULTS: Initially, 95% of patients had nephrotic syndrome with proteinuria of 3
      12 g per 24 hours, creatinine levels of 0.6-9.6 mg/dl, positive lupus serologies,
      and normal complement levels in 63%. Segmental and/or global collapsing
      glomerulopathy was seen in 11%-77% of glomeruli. Tubular atrophy with focal
      microcystic changes and interstitial fibrosis was seen in 35% of patients.
      Minimal glomerular mesangial deposits were noted in 63% of patients, and
      extensive foot process effacement was seen in 82% of patients. Initial treatment
      was with pulse/oral steroids. Follow-up from 13 patients revealed that 7 patients
      progressed to ESRD at the time of biopsy up to 21 months later, 1 patient
      returned to normal creatinine (1.1 mg/dl) without proteinuria, and 5 patients had
      creatinine of 1.2-3.6 mg/dl with proteinuria of 0.37-4 g per 24 hours.
      CONCLUSIONS: Collapsing glomerulopathy may be seen in SLE patients presenting
      with massive proteinuria with or without lupus nephritis, which may have
      prognostic significance.

PMID- 22461533
TI  - Electrocardiogram abnormalities and cardiovascular mortality in elderly patients
      with CKD.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular disease is the most common cause of
      death in CKD. This study evaluated whether electrocardiogram (ECG) abnormalities
      are predictors of cardiovascular death in CKD. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: The Cardiovascular Health Study limited database (1989-2005) was
      used to identify a cohort with CKD at baseline (estimated GFR < 60 mL/min per
      1.73 m(2)). The patients were categorized as having major, minor, or no ECG
      abnormalities. Rates of adjudicated cardiovascular events and mortality were
      compared among the groups using proportional hazards regression models. RESULTS:
      A total of 1192 participants had CKD at baseline; mean age +/- SD was 74.7+/-6.2
      years. Of these patients, 452 (38.8%) had major, 346 (29.7%) had minor, and 367
      (31.5%) had no ECG abnormalities. Participants with estimated GFR < 60 mL/min per
      1.73 m(2) were more likely to have ECG abnormalities at baseline (adjusted
      prevalence odds ratio, 1.23 [95% confidence interval (CI), 1.06-1.43]) than those
      with GFR >= 60 mL/min per 1.73 m(2). During mean follow-up of 10.3+/-3.8 years,
      814 (68.3%) participants died. Compared with participants without ECG
      abnormalities, participants with major abnormalities had the highest risk for
      cardiovascular events and death; adjusted hazard ratios were 2.15 (95% CI, 1.56
      2.98) and 2.27 (95% CI, 1.56-3.30), respectively. For minor ECG abnormalities,
      hazard ratios were 1.24 (95% CI, 0.91-1.70) and 1.48 (95% CI, 1.00-2.18),
      respectively. CONCLUSIONS: In patients with CKD, major ECG abnormalities are
      frequently present and predict a significantly higher risk for death and adverse
      cardiovascular outcomes.

PMID- 22461534
TI  - Leflunomide efficacy and pharmacodynamics for the treatment of BK viral
      infection.
AB  - BACKGROUND AND OBJECTIVES: BK virus is an infection in kidney transplantation
      patients jeopardizing graft survival. Unfortunately, there is no consensus on
      treatment of BK viremia and nephropathy. Leflunomide has been studied for the
      treatment of BK viremia and nephropathy, but there are limited data on the
      utility of leflunomide therapeutic drug monitoring. This study aimed to determine
      if a pharmacodynamic relationship exists between BK viral load reduction and
      leflunomide metabolite, A77 1726, serum concentrations. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This study was a retrospective, single-center,
      longitudinal analysis of patients identified with BK viremia with or without
      nephropathy. Patients were grouped according to whether they received
      leflunomide. All BK viral PCR and A77 1726 concentrations were analyzed to
      determine pharmacodynamics, and were correlated with clinical outcomes. RESULTS:
      Of 76 patients identified, 52 received leflunomide therapy and 24 did not.
      Patients who received leflunomide were further analyzed according to A77 1726
      concentrations and BK clearance; there was no difference in BK clearance. There
      was a lack of correlation between A77 1726 concentrations and log change in BK
      viral PCR concentration. Multivariate analysis demonstrated that mycophenolate
      mofetil discontinuation, BK viremia without nephropathy, and mean BK viral load
      were significantly associated with BK viral clearance; leflunomide use lacked
      this association. CONCLUSIONS: Pharmacodynamic analysis revealed no association
      between A77 1726 concentrations and BK viral PCR reductions. Multivariate
      analysis demonstrated that leflunomide therapy was not associated with BK viral
      clearance. Randomized studies are needed to determine the utility of leflunomide
      for BK viremia and nephropathy.

PMID- 22461536
TI  - Advance care planning in CKD/ESRD: an evolving process.
AB  - Advance care planning was historically considered to be simply the completion of
      a proxy (health care surrogate designation) or instruction (living will)
      directive that resulted from a conversation between a patient and his or her
      physician. We now know that advance care planning is a much more comprehensive
      and dynamic patient-centered process used by patients and families to strengthen
      relationships, achieve control over medical care, prepare for death, and clarify
      goals of care. Some advance directives, notably designated health care proxy
      documents, remain appropriate expressions of advance care planning. Moreover,
      although physician orders, such as do-not-resuscitate orders and Physician Orders
      for Life-Sustaining Treatment, may not be strictly defined as advance directives,
      their completion, when appropriate, is an integral component of advance care
      planning. The changing health circumstances and illness trajectory characteristic
      of ESRD mandate that advance care planning discussions adapt to a patient's
      situation and therefore must be readdressed at appropriate times and intervals.
      The options of withholding and withdrawing dialysis add ESRD-specific issues to
      advance care planning in this population and are events each nephrologist will at
      some time confront. Advance care planning is important throughout the spectrum of
      ESRD and is a part of nephrology practice that can be rewarding to nephrologists
      and beneficial to patients and their families.

PMID- 22461535
TI  - Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products
      in diabetic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Increased inflammation and oxidative stress may be
      caused by proteins and lipids modified by cytotoxic advanced glycation end
      products (AGEs) in food. Restricting food containing elevated AGEs improves these
      risk factors in diabetic CKD. Because diet adherence can be problematic, this
      study aimed to remove cytotoxic AGEs from food already ingested and to determine
      whether sevelamer carbonate sequesters cytotoxic AGEs in the gut, preventing
      their uptake and thereby reducing AGE-induced abnormalities. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This single-center, randomized, 2-month, open
      label, intention-to-treat, crossover study compared sevelamer carbonate with
      calcium carbonate treatment in stage 2-4 diabetic CKD. Participants received 2
      months of treatment with one drug, had a 1-week washout, and then received the
      opposite drug for 2 months. RESULTS: Sevelamer carbonate reduced HbA1c, serum
      methylglyoxal, serum (epsilon)N-carboxymethyl-lysine, triglycerides, and 8
      isoprostanes. Total cholesterol and fibroblast growth factor 23 were reduced by
      sevelamer carbonate, relative to calcium carbonate. AGE receptor 1 and sirtuin 1
      mRNA were increased and PMNC TNFalpha levels were decreased by sevelamer
      carbonate, but not calcium carbonate. Medications and caloric and AGE intake
      remained unchanged. Sevelamer carbonate reversibly bound AGE-BSA at intestinal,
      but not stomach, pH. CONCLUSIONS: Sevelamer carbonate significantly reduces
      HbA1c, fibroblast growth factor 23, lipids, and markers of inflammation and
      oxidative stress, and markedly increases antioxidant markers, independently of
      phosphorus in patients with diabetes and early kidney disease. These novel
      actions of sevelamer carbonate on metabolic and inflammatory abnormalities in
      type 2 diabetes mellitus may affect progression of early diabetic CKD.

PMID- 22461537
TI  - Association of statin use with risk and outcome of acute kidney injury in
      community-acquired pneumonia.
AB  - BACKGROUND AND OBJECTIVES: Sepsis is a leading cause of AKI. Animal studies
      suggest that the pleiotropic effect of statins attenuates the risk for AKI and
      decreases mortality. This study examined whether statin use was associated with a
      lower risk for pneumonia-induced AKI and 1-year and cause-specific mortality in
      patients with AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Multicenter,
      prospective cohort study of 1836 patients hospitalized with community-acquired
      pneumonia. RESULTS: Baseline characteristics differed among statin users and
      nonusers. Of the 413 patients (22.5%) who received a statin before
      hospitalization, statin treatment, when adjusted for differences in age, severity
      of pneumonia, admission from nursing home, health insurance, and propensity for
      statin use, did not reduce the risk for AKI (odds ratio [OR], 1.32 [95%
      confidence interval (CI), 1.02-1.69]; P=0.05). Of patients with AKI (n=631),
      statin use was associated with a lower risk for death at 1 year (27.8% versus
      38.8%; P=0.01), which was not significant when adjusted for differences in age,
      severity of pneumonia and AKI, use of mechanical ventilation, and propensity
      score (OR, 0.72 [95% CI, 0.50-1.06]; P=0.09). Among patients with AKI,
      cardiovascular disease accounted for one third of all deaths. CONCLUSIONS: In a
      large cohort of patients hospitalized with pneumonia, statins did not reduce the
      risk for AKI. Among patients with AKI, statin use was not associated with lower
      risk for death at 1 year. The higher risk for AKI observed among statin users may
      be due to indication bias.

PMID- 22461539
TI  - Cholesterol synthesis, cholesterol absorption, and mortality in hemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: Recent clinical trials on cholesterol-lowering in
      patients with CKD yielded conflicting results, which might have resulted from
      different treatment strategies. Serum cholesterol levels are determined by
      endogenous synthesis and intestinal absorption, which are differentially
      influenced by various classes of cholesterol-lowering agents. Assessing markers
      of cholesterol metabolism has thus been proposed for guidance of lipid-lowering
      therapy. This study analyzed surrogate markers of cholesterol absorption and
      synthesis in hemodialysis (HD) patients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: In 113 HD patients, lathosterol was measured as a marker of
      cholesterol synthesis and cholestanol was measured as a marker of cholesterol
      absorption via gas chromatography. Controls were 229 healthy persons. Overall
      survival in HD patients was recorded over 3.4-year follow-up. RESULTS: Compared
      with controls, HD patients had lower lathosterol and higher cholestanol levels
      (P<0.001 for both). During follow-up, 58 patients died; higher cholestanol
      (indicating higher cholesterol absorption) predicted poor outcome among HD
      patients in multivariate Cox regression analysis after adjustment for potential
      confounders (hazard ratio for cholestanol above median, 2.24 [95% confidence
      interval (CI), 1.29-3.89]; P=0.004), whereas lower lathosterol (indicating lower
      cholesterol synthesis) did not (hazard ratio for lathosterol below median, 1.43
      [95% CI, 0.81-2.50]; P=0.22). CONCLUSIONS: This analysis of markers of
      cholesterol metabolism characterizes HD patients as cholesterol absorbers. In
      longitudinal analysis, higher levels of cholestanol were associated with all
      cause mortality.

PMID- 22461538
TI  - Antibodies against linear epitopes on the Goodpasture autoantigen and kidney
      injury.
AB  - BACKGROUND AND OBJECTIVES: Linear epitopes on the Goodpasture autoantigen
      involved in human anti-glomerular basement membrane (GBM) disease are not fully
      defined. This study investigated the linear epitopes recognized by circulating
      antibodies in anti-GBM patients, aiming to identify the potential nephrogenic
      linear epitopes and their clinical significance. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Sixty-eight patients with anti-GBM disease were enrolled. Twenty
      four overlapping linear peptides were synthesized across the whole sequence of
      the human Goodpasture autoantigen. ELISA detected circulating antibodies against
      linear epitopes. Their associations with clinical features were further analyzed.
      RESULTS: Antibodies against linear peptides were detected in sera from 55
      patients (80.9%). Three major epitopes with high frequencies were identified: P14
      (41%), P16 (36.8%), and P18 (57%). P14, a formerly defined T cell epitope, was a
      mutual B cell epitope. Antibodies against P14 were frequently detected in
      patients with positive antineutrophil cytoplasmic antibodies (39.3% versus 12.5%;
      P=0.01). Patients with anti-P16 antibodies presented with higher serum creatinine
      on diagnosis (665.5+/-227.2 versus 443.7+/-296.8 MUmol/L; P=0.001) and worse
      renal outcome during follow-up (hazard ratio, 2.10; 95% confidence interval, 1.10
      3.90; P=0.02). The level of anti-P18 antibodies positively correlated with the
      percentage of crescents in glomeruli (r=0.54; P=0.008). Recognition of P22 was an
      independent predictor for patient death (hazard ratio, 3.02; 95% confidence
      interval, 1.20-7.57; P=0.02). CONCLUSIONS: Antibodies against linear epitopes on
      the Goodpasture autoantigen could be detected in human anti-GBM disease and were
      associated with kidney injury. P14 was a mutual T and B cell epitope, implying
      its nephrogenic role in disease initiation.

PMID- 22461540
TI  - Risk factors for dialysis withdrawal: an analysis of the Australia and New
      Zealand Dialysis and Transplant (ANZDATA) Registry, 1999-2008.
AB  - BACKGROUND AND OBJECTIVES: Dialysis withdrawal (DW) in patients with ESRD is
      increasing in importance. This study assessed causes of death and risk factors
      for DW in Australia and New Zealand in the first year of dialysis. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective observational cohort
      study included all adult Australians and New Zealanders beginning renal
      replacement therapy in 1999-2008. RESULTS: A total of 24,884 patients with 10,073
      deaths were included. Deaths from cardiac and social causes (predominantly DW)
      accounted for 38% and 28% of all deaths, respectively. Cumulative incidence of DW
      was 3.5% at 1 year (95% confidence interval [CI], 3.3%-3.8%), 9.0% at 3 years
      (95% CI, 8.6%-9.4%), and 13.4% at 5 years (95% CI, 12.8%-13.9%). In multivariate
      analysis, predictors for DW in the first year were older age (subhazard ratio
      [SHR], 1.70 per decade [95% CI, 1.59-1.83]; P<0.001), late referral (SHR, 1.83
      [95% CI, 1.59-2.11]; P<0.001), comorbid conditions (SHR, 1.33 per each additional
      comorbid condition [95% CI, 1.25-1.41]; P<0.001), and diabetes (SHR, 1.16 [95%
      CI, 1.00-1.34]; P=0.05). Negative predictors for DW included male sex (SHR, 0.75
      [95% CI, 0.66-0.87]; P<0.001), indigenous ethnicity (SHR, 0.74 [95% CI, 0.58
      0.95]; P=0.02), other nonwhite race (SHR, 0.66 [95% CI, 0.48-0.91]; P=0.01), and
      peritoneal dialysis user (SHR, 0.59 [95% CI, 0.49-0.72]; P<0.001). CONCLUSIONS:
      DW is common among dialysis patients in Australia and New Zealand. Risk factors
      include older age, female sex, white race, diabetes, higher comorbidity burden,
      hemodialysis user, and late referral to nephrologist.

PMID- 22461541
TI  - Genome sequence of Janthinobacterium sp. strain PAMC 25724, isolated from alpine
      glacier cryoconite.
AB  - The draft genome of Janthinobacterium sp. strain PAMC 25724, which is a violacein
      producing psychrotolerant bacterium, was determined. The strain was isolated from
      glacier cryoconite of the Alps mountain permafrost region. The sequence will
      allow identification and characterization of the genetic determination of its
      cold-adaptive properties.

PMID- 22461542
TI  - Genome sequence of extracellular-protease-producing Alishewanella jeotgali
      isolated from traditional Korean fermented seafood.
AB  - Alishewanella jeotgali MS1(T) (= KCTC 22429(T) = JCM 15561(T)) was isolated from
      a traditional Korean fermented seafood, gajami sikhae (jeotgal), and has been
      reported as a novel species. A. jeotgali was proven to have extracellular
      proteolytic activity, which may play an important role in the fermentation
      environment of food containing fish flesh. Here, we present the genome sequence
      of Alishewanella jeotgali MS1(T) as the first sequenced strain in the genus
      Alishewanella and its taxonomic relatives.

PMID- 22461543
TI  - Genome sequence of the human- and animal-pathogenic strain Nocardia
      cyriacigeorgica GUH-2.
AB  - The pathogenic strain Nocardia cyriacigeorgica GUH-2 was isolated from a fatal
      human nocardiosis case, and its genome was sequenced. The complete genomic
      sequence of this strain contains 6,194,645 bp, an average G+C content of 68.37%,
      and no plasmids. We also identified several protein-coding genes to which N.
      cyriacigeorgica's virulence can potentially be attributed.

PMID- 22461544
TI  - Genome sequence of the halophilic archaeon Halococcus hamelinensis.
AB  - Halococcus hamelinensis was isolated from hypersaline stromatolites in Shark Bay,
      Australia. Here we report the genome sequence (3,133,046 bp) of H. hamelinensis,
      which provides insights into the ecology, evolution, and adaptation of this novel
      microorganism.

PMID- 22461545
TI  - Complete genome sequence of Lactococcus lactis IO-1, a lactic acid bacterium that
      utilizes xylose and produces high levels of L-lactic acid.
AB  - We report the complete genome sequence of Lactococcus lactis IO-1 (= JCM7638). It
      is a nondairy lactic acid bacterium, produces nisin Z, ferments xylose, and
      produces predominantly L-lactic acid at high xylose concentrations. From ortholog
      analysis with other five L. lactis strains, IO-1 was identified as L. lactis
      subsp. lactis.

PMID- 22461546
TI  - Draft genome sequence of the shrimp pathogen Vibrio harveyi CAIM 1792.
AB  - Vibrio harveyi is a Gram-negative bacterium found in tropical and temperate
      marine environments as a free-living organism or in association with aquatic
      animals. We report the first sequenced genome of a Vibrio harveyi strain, CAIM
      1792, the etiologic agent of the "bright red" syndrome of the Pacific white
      shrimp Litopenaeus vannamei.

PMID- 22461547
TI  - Complete genome sequence of the African dairy isolate Streptococcus infantarius
      subsp. infantarius strain CJ18.
AB  - Streptococcus infantarius subsp. infantarius, a member of the Streptococcus
      bovis/Streptococcus equinus complex, is highly prevalent in artisanal dairy
      fermentations in Africa. Here the complete genome sequence of the dairy-adapted
      S. infantarius subsp. infantarius CJ18 strain--a strain predominant in
      traditionally fermented camel milk (suusac) from Kenya--is presented.

PMID- 22461548
TI  - Genome sequence of Staphylococcus aureus VC40, a vancomycin- and daptomycin
      resistant strain, to study the genetics of development of resistance to currently
      applied last-resort antibiotics.
AB  - The increasing emergence of multidrug-resistant Staphylococcus aureus is a
      problem of global importance. Here, we report the genome of S. aureus VC40, which
      is resistant to the last-resort antibiotics vancomycin and daptomycin. Its genome
      sequence will allow insights into the mechanisms that convey full resistance to
      these compounds.

PMID- 22461549
TI  - De novo genome project of Cupriavidus basilensis OR16.
AB  - Here we report on the complete genome sequence of Cupriavidus basilensis OR16
      NCAIM BO2487. The genome of strain OR16 contains 7,534 putative coding sequences,
      including a large set of xenobiotics-degrading genes and a unique glucose
      dehydrogenase gene that is absent from other Cupriavidus genomes.

PMID- 22461550
TI  - Genome sequence of Lactobacillus fructivorans KCTC 3543.
AB  - Lactobacillus fructivorans is important in the generation of particular flavors
      and in other ripening processes associated with fermented food. Here, we present
      the draft genome sequence of the type strain Lactobacillus fructivorans KCTC 3543
      (1,373,326 bp, with a G+C content of 38.9%), which consists of 5 scaffolds. The
      genome sequence was obtained by using a whole-genome shotgun strategy with Roche
      454 GS (FLX Titanium) pyrosequencing, and all of the reads were assembled using
      Newbler Assembler 2.3.

PMID- 22461551
TI  - Complete genome sequence of Rahnella sp. strain Y9602, a gammaproteobacterium
      isolate from metal- and radionuclide-contaminated soil.
AB  - Rahnella sp. strain Y9602 is a gammaproteobacterium isolated from contaminated
      subsurface soils that is capable of promoting uranium phosphate mineralization as
      a result of constitutive phosphatase activity. Here we report the first complete
      genome sequence of an isolate belonging to the genus Rahnella.

PMID- 22461552
TI  - Complete genome sequence of Salmonella enterica subsp. enterica serovar Typhi P
      stx-12.
AB  - We report here the complete genome sequence of Salmonella enterica subsp.
      enterica serovar Typhi P-stx-12, a clinical isolate obtained from a typhoid
      carrier in India.

PMID- 22461553
TI  - Genome sequence of Paenibacillus sp. strain Aloe-11, an endophytic bacterium with
      broad antimicrobial activity and intestinal colonization ability.
AB  - Paenibacillus sp. strain Aloe-11, a Gram-positive, spore-forming, facultatively
      anaerobic bacterium isolated from the root of Aloe chinensis in the southwest
      region of China, has excellent antibiotic activity and intestine colonization
      ability. Here, we present the 5.8-Mb draft genome sequence of Paenibacillus sp.
      strain Aloe-11.

PMID- 22461554
TI  - Genome sequence of "Candidatus Nitrosoarchaeum limnia" BG20, a low-salinity
      ammonia-oxidizing archaeon from the San Francisco Bay estuary.
AB  - Here, we present the draft genome sequence of "Candidatus Nitrosoarchaeum limnia"
      BG20, an ammonia-oxidizing archaeon enriched in culture from low-salinity
      sediments of the San Francisco Bay estuary. The genome sequence revealed many
      similarities to the previously sequenced genome of "Ca. Nitrosoarchaeum limnia"
      SFB1 (enriched from a nearby site in San Francisco Bay) and is representative of
      a clade of ammonia-oxidizing archaea (AOA) found in low-salinity habitats
      worldwide.

PMID- 22461555
TI  - Genome sequence of "Candidatus Nitrosopumilus salaria" BD31, an ammonia-oxidizing
      archaeon from the San Francisco Bay estuary.
AB  - Ammonia-oxidizing archaea (AOA) play important roles in nitrogen and carbon
      cycling in marine and terrestrial ecosystems. Here, we present the draft genome
      sequence for the ammonia-oxidizing archaeon "Candidatus Nitrosopumilus salaria"
      BD31, which was enriched in culture from sediments of the San Francisco Bay
      estuary. The genome sequences revealed many similarities to the genome of
      Nitrosopumilus maritimus.

PMID- 22461556
TI  - Complete genome sequence of Oceanimonas sp. GK1, a halotolerant bacterium from
      Gavkhouni Wetland in Iran.
AB  - Oceanimonas sp. GK1 (IBRC-M 10197) is a marine halotolerant gammaproteobacterium
      which was characterized as producing large amounts of poly-beta-hydroxybutyrate.
      Here we present the whole-genome sequence of Oceanimonas sp. GK1, which consists
      of a single circular chromosome of 3,514,537 bp and two plasmids 8,462 and 4,245
      bp in length.

PMID- 22461557
TI  - Draft genome sequence of the nontoxigenic Clostridium difficile strain CD37.
AB  - Here we report the draft genome sequence of Clostridium difficile strain CD37,
      the first nontoxigenic strain sequenced. Every sequenced strain of Clostridium
      difficile has been shown to contain multiple different mobile genetic elements.
      The draft genome sequence of strain CD37 reveals the presence of two putative
      conjugative transposons.

PMID- 22461558
TI  - Genome sequence of the pattern-forming social bacterium Paenibacillus
      dendritiformis C454 chiral morphotype.
AB  - Paenibacillus dendritiformis is a Gram-positive, soil-dwelling, spore-forming
      social microorganism. An intriguing collective faculty of this strain is
      manifested by its ability to switch between different morphotypes, such as the
      branching (T) and the chiral (C) morphotypes. Here we report the 6.3-Mb draft
      genome sequence of the P. dendritiformis C454 chiral morphotype.

PMID- 22461559
TI  - Notch-mediated patterning and cell fate allocation of pancreatic progenitor
      cells.
AB  - Early pancreatic morphogenesis is characterized by the transformation of an
      uncommitted pool of pancreatic progenitor cells into a branched pancreatic
      epithelium that consists of 'tip' and 'trunk' domains. These domains have
      distinct molecular signatures and differentiate into distinct pancreatic cell
      lineages. Cells at the branched tips of the epithelium develop into acinar cells,
      whereas cells in the trunk subcompartment differentiate into endocrine and duct
      cells. Recent genetic analyses have highlighted the role of key transcriptional
      regulators in the specification of these subcompartments. Here, we analyzed in
      mice the role of Notch signaling in the patterning of multipotent pancreatic
      progenitor cells through mosaic overexpression of a Notch signaling antagonist,
      dominant-negative mastermind-like 1, resulting in a mixture of wild-type and
      Notch-suppressed pancreatic progenitor cells. We find that attenuation of Notch
      signaling has pronounced patterning effects on multipotent pancreatic progenitor
      cells prior to terminal differentiation. Relative to the wild-type cells, the
      Notch-suppressed cells lose trunk marker genes and gain expression of tip marker
      genes. The Notch-suppressed cells subsequently differentiate into acinar cells,
      whereas duct and endocrine populations are formed predominantly from the wild
      type cells. Mechanistically, these observations could be explained by a
      requirement of Notch for the expression of the trunk determination gene Nkx6.1.
      This was supported by the finding of direct binding of RBP-jkappa to the Nkx6.1
      proximal promoter.

PMID- 22461560
TI  - WNT signaling increases proliferation and impairs differentiation of stem cells
      in the developing cerebellum.
AB  - The WNT pathway plays multiple roles in neural development and is crucial for
      establishment of the embryonic cerebellum. In addition, WNT pathway mutations are
      associated with medulloblastoma, the most common malignant brain tumor in
      children. However, the cell types within the cerebellum that are responsive to
      WNT signaling remain unknown. Here we investigate the effects of canonical WNT
      signaling on two important classes of progenitors in the developing cerebellum:
      multipotent neural stem cells (NSCs) and granule neuron precursors (GNPs). We
      show that WNT pathway activation in vitro promotes proliferation of NSCs but not
      GNPs. Moreover, mice that express activated beta-catenin in the cerebellar
      ventricular zone exhibit increased proliferation of NSCs in that region, whereas
      expression of the same protein in GNPs impairs proliferation. Although beta
      catenin-expressing NSCs proliferate they do not undergo prolonged expansion or
      neoplastic growth; rather, WNT signaling markedly interferes with their capacity
      for self-renewal and differentiation. At a molecular level, mutant NSCs exhibit
      increased expression of c-Myc, which might account for their transient
      proliferation, but also express high levels of bone morphogenetic proteins and
      the cyclin-dependent kinase inhibitor p21, which might contribute to their
      altered self-renewal and differentiation. These studies suggest that the WNT
      pathway is a potent regulator of cerebellar stem cell growth and differentiation.

PMID- 22461562
TI  - The role of hair cells, cilia and ciliary motility in otolith formation in the
      zebrafish otic vesicle.
AB  - Otoliths are biomineralised structures required for the sensation of gravity,
      linear acceleration and sound in the zebrafish ear. Otolith precursor particles,
      initially distributed throughout the otic vesicle lumen, become tethered to the
      tips of hair cell kinocilia (tether cilia) at the otic vesicle poles, forming two
      otoliths. We have used high-speed video microscopy to investigate the role of
      cilia and ciliary motility in otolith formation. In wild-type ears, groups of
      motile cilia are present at the otic vesicle poles, surrounding the immotile
      tether cilia. A few motile cilia are also found on the medial wall, but most
      cilia (92-98%) in the otic vesicle are immotile. In mutants with defective cilia
      (iguana) or ciliary motility (lrrc50), otoliths are frequently ectopic,
      untethered or fused. Nevertheless, neither cilia nor ciliary motility are
      absolutely required for otolith tethering: a mutant that lacks cilia completely
      (MZovl) is still capable of tethering otoliths at the otic vesicle poles. In
      embryos with attenuated Notch signalling [mindbomb mutant or Su(H) morphant],
      supernumerary hair cells develop and otolith precursor particles bind to the tips
      of all kinocilia, or bind directly to the hair cells' apical surface if cilia are
      absent [MZovl injected with a Su(H)1+2 morpholino]. However, if the first hair
      cells are missing (atoh1b morphant), otolith formation is severely disrupted and
      delayed. Our data support a model in which hair cells produce an otolith
      precursor-binding factor, normally localised to tether cell kinocilia. We also
      show that embryonic movement plays a minor role in the formation of normal
      otoliths.

PMID- 22461561
TI  - Wnt9b-dependent FGF signaling is crucial for outgrowth of the nasal and maxillary
      processes during upper jaw and lip development.
AB  - Outgrowth and fusion of the lateral and medial nasal processes and of the
      maxillary process of the first branchial arch are integral to lip and primary
      palate development. Wnt9b mutations are associated with cleft lip and cleft
      palate in mice; however, the cause of these defects remains unknown. Here, we
      report that Wnt9b(-/-) mice show significantly retarded outgrowth of the nasal
      and maxillary processes due to reduced proliferation of mesenchymal cells, which
      subsequently results in a failure of physical contact between the facial
      processes that leads to cleft lip and cleft palate. These cellular defects in
      Wnt9b(-/-) mice are mainly caused by reduced FGF family gene expression and FGF
      signaling activity resulting from compromised canonical WNT/beta-catenin
      signaling. Our study has identified a previously unknown regulatory link between
      WNT9B and FGF signaling during lip and upper jaw development.

PMID- 22461564
TI  - A GATA/homeodomain transcriptional code regulates axon guidance through the Unc-5
      receptor.
AB  - Transcription factor codes play an essential role in neuronal specification and
      axonal guidance in both vertebrate and invertebrate organisms. However, how
      transcription codes regulate axon pathfinding remains poorly understood. One such
      code defined by the homeodomain transcription factor Even-skipped (Eve) and by
      the GATA 2/3 homologue Grain (Grn) is specifically required for motor axon
      projection towards dorsal muscles in Drosophila. Using different mutant
      combinations, we present genetic evidence that both Grn and Eve are in the same
      pathway as Unc-5 in dorsal motoneurons (dMNs). In grn mutants, in which dMNs fail
      to reach their muscle targets, dMNs show significantly reduced levels of unc-5
      mRNA expression and this phenotype can be partially rescued by the reintroduction
      of unc-5. We also show that both eve and grn are required independently to induce
      expression of unc-5 in dMNs. Reconstitution of the eve-grn transcriptional code
      of a dMN in dMP2 neurons, which do not project to lateral muscles in Drosophila,
      is able to reprogramme those cells accordingly; they robustly express unc-5 and
      project towards the muscle field as dMNs. Each transcription factor can
      independently induce unc-5 expression but unc-5 expression is more robust when
      both factors are expressed together. Furthermore, dMP2 exit is dependent on the
      level of unc-5 induced by eve and grn. Taken together, our data strongly suggests
      that the eve-grn transcriptional code controls axon guidance, in part, by
      regulating the level of unc-5 expression.

PMID- 22461563
TI  - p120-catenin is essential for terminal end bud function and mammary
      morphogenesis.
AB  - Although p120-catenin (p120) is crucial for E-cadherin function, ablation
      experiments in epithelial tissues from different organ systems reveal markedly
      different effects. Here, we examine for the first time the consequences of p120
      knockout during mouse mammary gland development. An MMTV-Cre driver was used to
      target knockout to the epithelium at the onset of puberty. p120 ablation was
      detected in approximately one-quarter of the nascent epithelium at the forth week
      post-partum. However, p120 null cells were essentially nonadherent, excluded from
      the process of terminal end bud (TEB) morphogenesis and lost altogether by week
      six. This elimination process caused a delay in TEB outgrowth, after which the
      gland developed normally from cells that had retained p120. Mechanistic studies
      in vitro indicate that TEB dysfunction is likely to stem from striking E-cadherin
      loss, failure of cell-cell adhesion and near total exclusion from the collective
      migration process. Our findings reveal an essential role for p120 in mammary
      morphogenesis.

PMID- 22461565
TI  - The regulation of glial-specific splicing of Neurexin IV requires HOW and Cdk12
      activity.
AB  - The differentiation of the blood-brain barrier (BBB) is an essential process in
      the development of a complex nervous system and depends on alternative splicing.
      In the fly BBB, glial cells establish intensive septate junctions that require
      the cell-adhesion molecule Neurexin IV. Alternative splicing generates two
      different Neurexin IV isoforms: Neurexin IV(exon3), which is found in cells that
      form septate junctions, and Neurexin IV(exon4), which is found in neurons that
      form no septate junctions. Here, we show that the formation of the BBB depends on
      the RNA-binding protein HOW (Held out wings), which triggers glial specific
      splicing of Neurexin IV(exon3). Using a set of splice reporters, we show that one
      HOW-binding site is needed to include one of the two mutually exclusive exons 3
      and 4, whereas binding at the three further motifs is needed to exclude exon 4.
      The differential splicing is controlled by nuclear access of HOW and can be
      induced in neurons following expression of nuclear HOW. Using a novel in vivo two
      color splicing detector, we then screened for genes required for full HOW
      activity. This approach identified Cyclin-dependent kinase 12 (Cdk12) and the
      splicesosomal component Prp40 as major determinants in regulating HOW-dependent
      splicing of Neurexin IV. Thus, in addition to the control of nuclear localization
      of HOW, the phosphorylation of the C-terminal domain of the RNA polymerase II by
      Cdk12 provides an elegant mechanism in regulating timed splicing of newly
      synthesized mRNA molecules.

PMID- 22461566
TI  - Hypothalamic neuropeptide Y (NPY) controls hepatic VLDL-triglyceride secretion in
      rats via the sympathetic nervous system.
AB  - Excessive secretion of triglyceride-rich very low-density lipoproteins (VLDL-TG)
      contributes to diabetic dyslipidemia. Earlier studies have indicated a possible
      role for the hypothalamus and autonomic nervous system in the regulation of VLDL
      TG. In the current study, we investigated whether the autonomic nervous system
      and hypothalamic neuropeptide Y (NPY) release during fasting regulates hepatic
      VLDL-TG secretion. We report that, in fasted rats, an intact hypothalamic arcuate
      nucleus and hepatic sympathetic innervation are necessary to maintain VLDL-TG
      secretion. Furthermore, the hepatic sympathetic innervation is necessary to
      mediate the stimulatory effect of intracerebroventricular administration of NPY
      on VLDL-TG secretion. Since the intracerebroventricular administration of NPY
      increases VLDL-TG secretion by the liver without affecting lipolysis, its effect
      on lipid metabolism appears to be selective to the liver. Together, our findings
      indicate that the increased release of NPY during fasting stimulates the
      sympathetic nervous system to maintain VLDL-TG secretion at a postprandial level.

PMID- 22461567
TI  - Diabetes-associated common genetic variation and its association with GLP-1
      concentrations and response to exogenous GLP-1.
AB  - The mechanisms by which common genetic variation predisposes to type 2 diabetes
      remain unclear. The disease-associated variants in TCF7L2 (rs7903146) and WFS1
      (rs10010131) have been shown to affect response to exogenous glucagon-like
      peptide 1 (GLP-1), while variants in KCNQ1 (rs151290, rs2237892, and rs2237895)
      alter endogenous GLP-1 secretion. We set out to validate these observations using
      a model of GLP-1-induced insulin secretion. We studied healthy individuals using
      a hyperglycemic clamp and GLP-1 infusion. In addition, we measured active and
      total GLP-1 in response to an oral challenge in nondiabetic subjects. After
      genotyping the relevant single nucleotide polymorphisms, generalized linear
      regression models and repeated-measures ANCOVA models incorporating potential
      confounders, such as age and BMI, were used to assess the associations, if any,
      of response with genotype. These variants did not alter GLP-1 concentrations in
      response to oral intake. No effects on beta-cell responsiveness to hyperglycemia
      and GLP-1 infusion were apparent. Diabetes-associated variation (T allele at
      rs7903146) in TCF7L2 may impair the ability of hyperglycemia to suppress glucagon
      (45 +/- 2 vs. 47 +/- 2 vs. 60 +/- 5 ng/L for CC, CT, and TT, respectively, P =
      0.02). In nondiabetic subjects, diabetes-associated genetic variation does not
      alter GLP-1 concentrations after an oral challenge or its effect on insulin
      secretion.

PMID- 22461569
TI  - Higher breastfeeding intensity associated with improved postpartum glucose
      metabolism in women with recent gestational diabetes.

PMID- 22461568
TI  - Early postnatal caloric restriction protects adult male intrauterine growth
      restricted offspring from obesity.
AB  - Postnatal ad libitum caloric intake superimposed on intrauterine growth
      restriction (IUGR) is associated with adult-onset obesity, insulin resistance,
      and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of
      prenatal nutrient deprivation-induced programming can be reversed with the
      introduction of early postnatal calorie restriction. Ten-month-old male rats
      exposed to either prenatal nutrient restriction with ad libitum postnatal intake
      (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient
      restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21)
      (PNGR) were compared with age-matched controls (CON). Visceral adiposity,
      metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps
      were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase
      in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin
      sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON.
      The IPGR group remained lean, euglycemic, insulin sensitive, and active while
      maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar
      to IPGR, but less active while maintaining metabolic flexibility. We conclude
      that IUGR resulted in obesity without insulin resistance and energy metabolic
      perturbations prior to development of glucose intolerance and T2DM. Postnatal
      nutrient restriction superimposed on IUGR was protective, restoring metabolic
      normalcy to a lean and active phenotype.

PMID- 22461570
TI  - Interviews of 21 adolescents reveal a desire for structured education programme
      specifically tailored to their needs.

PMID- 22461571
TI  - Meaning of zero coronary calcium score in symptomatic patients referred for
      coronary computed tomographic angiography.
AB  - AIMS: The clinical implication of a zero coronary calcium score (CCS) in patients
      with chest pain syndrome has been under debate. This study was undertaken to
      determine the meaning of a CCS of zero in a large sample of symptomatic patients
      referred for coronary computed tomographic (CT) angiography. METHODS AND RESULTS:
      We consecutively enrolled 2088 patients (age 58 +/- 10 years, 1028 men) who had
      undergone 64-slice cardiac CT due to chest pain syndrome. A CCS of zero was
      detected in 1114 patients (471 men and 643 women). Of these 1114 patients,
      obstructive coronary artery disease (CAD) was found in a total of 48 patients
      (4.3%); 35 men (7.4%) and 13 women (2.0%). Among the zero CCS patients with
      obstructive CAD, men had a higher prevalence of both premature CAD (49 vs. 0%)
      and multivessel disease (20 vs. 8%) than women. During the follow-up period (1033
      +/- 136 days), early revascularization was done in 25 patients (2.2%, 18 men and
      7 women) and there were 14 major adverse cardiac events (1.3%, 8 men and 7 women)
      among the zero CCS patients. CAD severity was a strong prognostic indicator in
      the zero CCS patients. CONCLUSION: A CCS of zero cannot be used by itself to
      exclude obstructive CAD in symptomatic patients referred for coronary CT
      angiography (CCTA). The prevalence of obstructive CAD and adverse cardiac events
      are not negligible in symptomatic patients with a CCS of zero, and CAD severity
      by CCTA is associated with higher rates of adverse cardiac event.

PMID- 22461573
TI  - Engage to excel.

PMID- 22461572
TI  - Localised myocardial scar related to left ventricular false tendons.

PMID- 22461578
TI  - Particle physics. DOE derails planning for major Fermilab experiment.

PMID- 22461579
TI  - Clinical medicine. Biomarker tests need closer scrutiny, IOM concludes.

PMID- 22461580
TI  - Agriculture. Field research on bees raises concern about low-dose pesticides.

PMID- 22461582
TI  - Nonproliferation. North Korea conundrum overshadows nuclear summit.

PMID- 22461581
TI  - Ocean science. U.S. budget cuts threaten to sink undersea research fleet.

PMID- 22461583
TI  - Psychology research. Psychology's bold initiative.

PMID- 22461584
TI  - Microscopy. New lens offers scientist a brighter outlook.

PMID- 22461585
TI  - Radio astronomy. Partners prepare to pick a site for world's biggest telescope.

PMID- 22461586
TI  - Electronic textbooks: why the rush?

PMID- 22461587
TI  - Protecting Brazil's coastal wetlands.

PMID- 22461590
TI  - Comment on "Disentangling the drivers of beta diversity along latitudinal and
      elevational gradients".
AB  - Kraft et al. (Report, 23 September 2011, p. 1755) analyzed two data sets and
      concluded that "there is no need to invoke differences in the mechanisms of
      community assembly in temperate versus tropical systems to explain these global
      scale patterns of beta diversity." We show that their conclusion is based on
      inappropriate data and inadequate methods of analysis.

PMID- 22461591
TI  - Comment on "Disentangling the drivers of beta diversity along latitudinal and
      elevational gradients".
AB  - Kraft et al. (Report, 23 September 2011, p. 1755) argued that the latitudinal
      trend in beta diversity is spurious and just reflects a trend in gamma diversity.
      Their results depend on the idiosyncrasies of their data, especially the
      latitudinally varying degree of undersampling and a local sampling setup that is
      not suitable for analyzing drivers of beta diversity.

PMID- 22461593
TI  - India's path to knowledge.

PMID- 22461594
TI  - Research ethics. To protect human subjects, review what was done, not proposed.

PMID- 22461595
TI  - Cell biology. Rapamycin paradox resolved.

PMID- 22461596
TI  - Computer science. How smart is your home?

PMID- 22461597
TI  - Computer science. How smart is your city?

PMID- 22461599
TI  - Physics. A single spin feels the vibrations.

PMID- 22461598
TI  - Neuroscience. Segregation and wiring in the brain.

PMID- 22461600
TI  - Geochemistry. Keeping time with Earth's heaviest element.

PMID- 22461601
TI  - Retrospective. Renato Dulbecco (1914-2012).

PMID- 22461602
TI  - IBI* series winner. Investigating Arabia Mountain: a molecular approach.

PMID- 22461603
TI  - IBI* series winner. Adapting to osmotic stress and the process of science.

PMID- 22461604
TI  - Integrated electromicrobial conversion of CO2 to higher alcohols.
AB  - One of the major challenges in using electrical energy is the efficiency in its
      storage. Current methods, such as chemical batteries, hydraulic pumping, and
      water splitting, suffer from low energy density or incompatibility with current
      transportation infrastructure. Here, we report a method to store electrical
      energy as chemical energy in higher alcohols, which can be used as liquid
      transportation fuels. We genetically engineered a lithoautotrophic microorganism,
      Ralstonia eutropha H16, to produce isobutanol and 3-methyl-1-butanol in an
      electro-bioreactor using CO(2) as the sole carbon source and electricity as the
      sole energy input. The process integrates electrochemical formate production and
      biological CO(2) fixation and higher alcohol synthesis, opening the possibility
      of electricity-driven bioconversion of CO(2) to commercial chemicals.

PMID- 22461605
TI  - Emerging chirality in artificial spin ice.
AB  - Artificial spin ice, made up of planar nanostructured arrays of simple
      ferromagnetic bars, is a playground for rich physics associated with the spin
      alignment of the bars and spin texture associated with the magnetic frustration
      at the bar vertices. The phase diagram is exotic, showing magnetic monopole-like
      defects and liquid and solid phases of spins arranged in loop states with
      predicted chiral order. We show that magnetotransport measurements in connected
      honeycomb structures yield the onset of an anomalous Hall signal at 50 kelvin.
      The temperature scale can be attributed to the long-range dipolar ice phase. The
      topological Hall signal arises because chiral loops form at the sample edges,
      indicating a generic route to exotic states via nanoarray edge structure.

PMID- 22461606
TI  - Disentangling the electronic and phononic glue in a high-Tc superconductor.
AB  - Unveiling the nature of the bosonic excitations that mediate the formation of
      Cooper pairs is a key issue for understanding unconventional superconductivity. A
      fundamental step toward this goal would be to identify the relative weight of the
      electronic and phononic contributions to the overall frequency (Omega)-dependent
      bosonic function, Pi(Omega). We performed optical spectroscopy on
      Bi(2)Sr(2)Ca(0.92)Y(0.08)Cu(2)O(8+delta) crystals with simultaneous time and
      frequency resolution; this technique allowed us to disentangle the electronic and
      phononic contributions by their different temporal evolution. The spectral
      distribution of the electronic excitations and the strength of their interaction
      with fermionic quasiparticles fully account for the high critical temperature of
      the superconducting phase transition.

PMID- 22461607
TI  - Hydrocarbon separations in a metal-organic framework with open iron(II)
      coordination sites.
AB  - The energy costs associated with large-scale industrial separation of light
      hydrocarbons by cryogenic distillation could potentially be lowered through
      development of selective solid adsorbents that operate at higher temperatures.
      Here, the metal-organic framework Fe(2)(dobdc) (dobdc(4-) : 2,5-dioxido-1,4
      benzenedicarboxylate) is demonstrated to exhibit excellent performance
      characteristics for separation of ethylene/ethane and propylene/propane mixtures
      at 318 kelvin. Breakthrough data obtained for these mixtures provide experimental
      validation of simulations, which in turn predict high selectivities and
      capacities of this material for the fractionation of
      methane/ethane/ethylene/acetylene mixtures, removal of acetylene impurities from
      ethylene, and membrane-based olefin/paraffin separations. Neutron powder
      diffraction data confirm a side-on coordination of acetylene, ethylene, and
      propylene at the iron(II) centers, while also providing solid-state structural
      characterization of the much weaker interactions of ethane and propane with the
      metal.

PMID- 22461608
TI  - 238U/235U Systematics in terrestrial uranium-bearing minerals.
AB  - The present-day (238)U/(235)U ratio has fundamental implications for uranium-lead
      geochronology and cosmochronology. A value of 137.88 has previously been
      considered invariant and has been used without uncertainty to calculate
      terrestrial mineral ages. We report high-precision (238)U/(235)U measurements for
      a suite of uranium-bearing minerals from 58 samples representing a diverse range
      of lithologies. This data set exhibits a range in (238)U/(235)U values of >5 per
      mil, with no clear relation to any petrogenetic, secular, or regional trends.
      Variation between comagmatic minerals suggests that (238)U/(235)U fractionation
      processes operate at magmatic temperatures. A mean (238)U/(235)U value of 137.818
      +/- 0.045 (2sigma) in zircon samples reflects the average uranium isotopic
      composition and variability of terrestrial zircon. This distribution is broadly
      representative of the average crustal and "bulk Earth" (238)U/(235)U composition.

PMID- 22461609
TI  - A shorter 146Sm half-life measured and implications for 146Sm-142Nd chronology in
      the solar system.
AB  - The extinct p-process nuclide (146)Sm serves as an astrophysical and geochemical
      chronometer through measurements of isotopic anomalies of its alpha-decay
      daughter (142)Nd. Based on analyses of (146)Sm/(147)Sm alpha-activity and atom
      ratios, we determined the half-life of (146)Sm to be 68 +/- 7 (1sigma) million
      years, which is shorter than the currently used value of 103 +/- 5 million years.
      This half-life value implies a higher initial (146)Sm abundance in the early
      solar system, ((146)Sm/(144)Sm)(0) = 0.0094 +/- 0.0005 (2sigma), than previously
      estimated. Terrestrial, lunar, and martian planetary silicate mantle
      differentiation events dated with (146)Sm-(142)Nd converge to a shorter time span
      and in general to earlier times, due to the combined effect of the new (146)Sm
      half-life and ((146)Sm/(144)Sm)(0) values.

PMID- 22461610
TI  - Control of sleep by cyclin A and its regulator.
AB  - How and why the brain reversibly switches from a waking to a sleep state remain
      among the most intriguing questions in biology. We show that cyclin A (CycA) and
      regulator of cyclin A1, essential cell cycle factors, function in postmitotic
      neurons to promote sleep in Drosophila melanogaster. Reducing the abundance of
      CycA in neurons delayed the wake-sleep transition, caused multiple arousals from
      sleep, and reduced the homeostatic response to sleep deprivation. CycA is
      expressed in ~40 to 50 neurons in the adult brain, most of which are intermingled
      with circadian clock neurons, suggesting functional interactions among neurons
      controlling sleep and circadian behavior.

PMID- 22461611
TI  - Cotranscriptional role for Arabidopsis DICER-LIKE 4 in transcription termination.
AB  - Transcription termination is emerging as an important component of gene
      regulation necessary to partition the genome and minimize transcriptional
      interference. We have discovered a role for the Arabidopsis RNA silencing enzyme
      DICER-LIKE 4 (DCL4) in transcription termination of an endogenous Arabidopsis
      gene, FCA. DCL4 directly associates with FCA chromatin in the 3' region and
      promotes cleavage of the nascent transcript in a domain downstream of the
      canonical polyA site. In a dcl4 mutant, the resulting transcriptional read
      through triggers an RNA interference-mediated gene silencing of a transgene
      containing the same 3' region. We conclude that DCL4 promotes transcription
      termination of the Arabidopsis FCA gene, reducing the amount of aberrant RNA
      produced from the locus.

PMID- 22461612
TI  - The geometric structure of the brain fiber pathways.
AB  - The structure of the brain as a product of morphogenesis is difficult to
      reconcile with the observed complexity of cerebral connectivity. We therefore
      analyzed relationships of adjacency and crossing between cerebral fiber pathways
      in four nonhuman primate species and in humans by using diffusion magnetic
      resonance imaging. The cerebral fiber pathways formed a rectilinear three
      dimensional grid continuous with the three principal axes of development. Cortico
      cortical pathways formed parallel sheets of interwoven paths in the longitudinal
      and medio-lateral axes, in which major pathways were local condensations. Cross
      species homology was strong and showed emergence of complex gyral connectivity by
      continuous elaboration of this grid structure. This architecture naturally
      supports functional spatio-temporal coherence, developmental path-finding, and
      incremental rewiring with correlated adaptation of structure and function in
      cerebral plasticity and evolution.

PMID- 22461613
TI  - Hierarchical genetic organization of human cortical surface area.
AB  - Surface area of the cerebral cortex is a highly heritable trait, yet little is
      known about genetic influences on regional cortical differentiation in humans.
      Using a data-driven, fuzzy clustering technique with magnetic resonance imaging
      data from 406 twins, we parceled cortical surface area into genetic subdivisions,
      creating a human brain atlas based solely on genetically informative data.
      Boundaries of the genetic divisions corresponded largely to meaningful structural
      and functional regions; however, the divisions represented previously undescribed
      phenotypes different from conventional (non-genetically based) parcellation
      systems. The genetic organization of cortical area was hierarchical, modular, and
      predominantly bilaterally symmetric across hemispheres. We also found that the
      results were consistent with human-specific regions being subdivisions of
      previously described, genetically based lobar regionalization patterns.

PMID- 22461614
TI  - Ecological context influences epidemic size and parasite-driven evolution.
AB  - The occurrence and magnitude of disease outbreaks can strongly influence host
      evolution. In particular, when hosts face a resistance-fecundity trade-off, they
      might evolve increased resistance to infection during larger epidemics but
      increased susceptibility during smaller ones. We tested this theoretical
      prediction by using a zooplankton-yeast host-parasite system in which ecological
      factors determine epidemic size. Lakes with high productivity and low predation
      pressure had large yeast epidemics; during these outbreaks, hosts became more
      resistant to infection. However, with low productivity and high predation,
      epidemics remained small and hosts evolved increased susceptibility. Thus, by
      modulating disease outbreaks, ecological context (productivity and predation)
      shaped host evolution during epidemics. Consequently, anthropogenic alteration of
      productivity and predation might strongly influence both ecological and
      evolutionary outcomes of disease.

PMID- 22461616
TI  - hnRNP C tetramer measures RNA length to classify RNA polymerase II transcripts
      for export.
AB  - Specific RNA recognition is usually achieved by specific RNA sequences and/or
      structures. However, we show here a mechanism by which RNA polymerase II (Pol II)
      transcripts are classified according to their length. The heterotetramer of the
      heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2 measures the length of the
      transcripts like a molecular ruler, by selectively binding to the unstructured
      RNA regions longer than 200 to 300 nucleotides. Thus, the tetramer sorts the
      transcripts into two RNA categories, to be exported as either messenger RNA or
      uridine-rich small nuclear RNA (U snRNA), depending on whether or not they are
      longer than the threshold, respectively. Our findings reveal a new function of
      the C tetramer and highlight the biological importance of RNA recognition by the
      length.

PMID- 22461615
TI  - Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled
      from longevity.
AB  - Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1),
      extends the life spans of yeast, flies, and mice. Calorie restriction, which
      increases life span and insulin sensitivity, is proposed to function by
      inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin
      substantially impairs glucose tolerance and insulin action. We demonstrate that
      rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was
      required for the insulin-mediated suppression of hepatic gluconeogenesis.
      Further, decreased mTORC1 signaling was sufficient to extend life span
      independently from changes in glucose homeostasis, as female mice heterozygous
      for both mTOR and mLST8 exhibited decreased mTORC1 activity and extended life
      span but had normal glucose tolerance and insulin sensitivity. Thus, mTORC2
      disruption is an important mediator of the effects of rapamycin in vivo.

PMID- 22461618
TI  - Novel dextranase catalyzing cycloisomaltooligosaccharide formation and
      identification of catalytic amino acids and their functions using chemical rescue
      approach.
AB  - A novel endodextranase from Paenibacillus sp. (Paenibacillus sp. dextranase;
      PsDex) was found to mainly produce isomaltotetraose and small amounts of
      cycloisomaltooligosaccharides (CIs) with a degree of polymerization of 7-14 from
      dextran. The 1,696-amino acid sequence belonging to the glycosyl hydrolase family
      66 (GH-66) has a long insertion (632 residues; Thr(451)-Val(1082)), a portion of
      which shares identity (35% at Ala(39)-Ser(1304) of PsDex) with Pro(32)-Ala(755)
      of CI glucanotransferase (CITase), a GH-66 enzyme that catalyzes the formation of
      CIs from dextran. This homologous sequence (Val(837)-Met(932) for PsDex and
      Tyr(404)-Tyr(492) for CITase), similar to carbohydrate-binding module 35, was not
      found in other endodextranases (Dexs) devoid of CITase activity. These results
      support the classification of GH-66 enzymes into three types: (i) Dex showing
      only dextranolytic activity, (ii) Dex catalyzing hydrolysis with low cyclization
      activity, and (iii) CITase showing CI-forming activity with low dextranolytic
      activity. The fact that a C-terminal truncated enzyme (having Ala(39)-Ser(1304))
      has 50% wild-type PsDex activity indicates that the C-terminal 392 residues are
      not involved in hydrolysis. GH-66 enzymes possess four conserved acidic residues
      (Asp(189), Asp(340), Glu(412), and Asp(1254) of PsDex) of catalytic candidates.
      Their amide mutants decreased activity (1/1,500 to 1/40,000 times), and D1254N
      had 36% activity. A chemical rescue approach was applied to D189A, D340G, and
      E412Q using alpha-isomaltotetraosyl fluoride with NaN(3). D340G or E412Q formed a
      beta- or alpha-isomaltotetraosyl azide, respectively, strongly indicating
      Asp(340) and Glu(412) as a nucleophile and acid/base catalyst, respectively.
      Interestingly, D189A synthesized small sized dextran from alpha-isomaltotetraosyl
      fluoride in the presence of NaN(3).

PMID- 22461617
TI  - GATA4 is a critical regulator of gonadectomy-induced adrenocortical tumorigenesis
      in mice.
AB  - In response to gonadectomy certain inbred mouse strains develop sex steroidogenic
      adrenocortical neoplasms. One of the hallmarks of neoplastic transformation is
      expression of GATA4, a transcription factor normally present in gonadal but not
      adrenal steroidogenic cells of the adult mouse. To show that GATA4 directly
      modulates adrenocortical tumorigenesis and is not merely a marker of gonadal-like
      differentiation in the neoplasms, we studied mice with germline or conditional
      loss-of-function mutations in the Gata4 gene. Germline Gata4 haploinsufficiency
      was associated with attenuated tumor growth and reduced expression of sex
      steroidogenic genes in the adrenal glands of ovariectomized B6D2F1 and B6AF1
      mice. At 12 months after ovariectomy, wild-type B6D2F1 mice had biochemical and
      histological evidence of adrenocortical estrogen production, whereas Gata4(+/-)
      B6D2F1 mice did not. Germline Gata4 haploinsufficiency exacerbated the secondary
      phenotype of postovariectomy obesity in B6D2F1 mice, presumably by limiting
      ectopic estrogen production in the adrenal glands. Amhr2-cre-mediated deletion of
      floxed Gata4 (Gata4(F)) in nascent adrenocortical neoplasms of ovariectomized
      B6.129 mice reduced tumor growth and the expression of gonadal-like markers in a
      Gata4(F) dose-dependent manner. We conclude that GATA4 is a key modifier of
      gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex
      steroidogenic cell differentiation.

PMID- 22461619
TI  - P2X7 receptor-mediated scavenger activity of mononuclear phagocytes toward non
      opsonized particles and apoptotic cells is inhibited by serum glycoproteins but
      remains active in cerebrospinal fluid.
AB  - Rapid phagocytosis of non-opsonized particles including apoptotic cells is an
      important process that involves direct recognition of the target by multiple
      scavenger receptors including P2X7 on the phagocyte surface. Using a real-time
      phagocytosis assay, we studied the effect of serum proteins on this phagocytic
      process. Inclusion of 1-5% serum completely abolished phagocytosis of non
      opsonized YG beads by human monocytes. Inhibition was reversed by pretreatment of
      serum with 1-10 mM tetraethylenepentamine, a copper/zinc chelator. Inhibitory
      proteins from the serum were determined as negatively charged glycoproteins (pI <
      6) with molecular masses between 100 and 300 kDa. A glycoprotein-rich inhibitory
      fraction of serum not only abolished YG bead uptake but also inhibited
      phagocytosis of apoptotic lymphocytes or neuronal cells by human monocyte-derived
      macrophages. Three copper- and/or zinc-containing serum glycoproteins,
      ceruloplasmin, serum amyloid P-component, and amyloid precursor protein, were
      identified, and the purified proteins were shown to inhibit the phagocytosis of
      beads by monocytes as well as phagocytosis of apoptotic neuronal cells by
      macrophages. Human adult cerebrospinal fluid, which contains very little
      glycoprotein, had no inhibitory effect on phagocytosis of either beads or
      apoptotic cells. These data suggest for the first time that metal-interacting
      glycoproteins present within serum are able to inhibit the scavenger activity of
      mononuclear phagocytes toward insoluble debris and apoptotic cells.

PMID- 22461620
TI  - Saccharomyces cerevisiae porin pore forms complexes with mitochondrial outer
      membrane proteins Om14p and Om45p.
AB  - Numerous transport processes occur between the two mitochondrial (mt) membranes
      due to the diverse functions and metabolic processes of the mt organelle. The
      metabolite and ion transport through the mt outer membrane (OM) is widely assumed
      to be mediated by the porin pore, whereas in the mt inner membrane (IM) specific
      carriers are responsible for transport processes. Here, we provide evidence by
      means of Blue Native (BN)-PAGE analysis, co-immunoprecipitation, and tandem
      affinity purification that the two mt OM proteins Om14p and Om45p associate with
      the porin pore. Porin molecules seem to assemble independently to build the core
      unit. A subpopulation of these core units interacts with Om14p and Om45p. With
      preparative tandem affinity purification followed by MS analysis, we could
      identify interaction partners of this OM complex, which are mainly localized
      within the mt IM and function as carriers for diverse molecules. We propose a
      model for the role of the two OM proteins in addressing the porin pore to bind to
      specific channels in the mt IM to facilitate transport of metabolites.

PMID- 22461621
TI  - Role of inflammasomes in host defense against Citrobacter rodentium infection.
AB  - Citrobacter rodentium is an enteric bacterial pathogen of the mouse intestinal
      tract that triggers inflammatory responses resembling those of humans infected
      with enteropathogenic and enterohemorrhagic Escherichia coli. Inflammasome
      signaling is emerging as a central regulator of inflammatory and host responses
      to several pathogens, but the in vivo role of inflammasome signaling in host
      defense against C. rodentium has not been characterized. Here, we show that mice
      lacking the inflammasome components Nlrp3, Nlrc4, and caspase-1 were
      hypersusceptible to C. rodentium-induced gastrointestinal inflammation. This was
      due to defective interleukin (IL)-1beta and IL-18 production given that il-1beta(
      /-) and il-18(-/-) mice also suffered from increased bacterial burdens and
      exacerbated histopathology. C. rodentium specifically activated the Nlrp3
      inflammasome in in vitro-infected macrophages independently of a functional
      bacterial type III secretion system. Thus, production of IL-1beta and IL-18
      downstream of the Nlrp3 and Nlrc4 inflammasomes plays a critical role in host
      defense against enteric infections caused by C. rodentium.

PMID- 22461622
TI  - Elucidating essential role of conserved carboxysomal protein CcmN reveals common
      feature of bacterial microcompartment assembly.
AB  - Bacterial microcompartments are organelles composed of a protein shell that
      surrounds functionally related proteins. Bioinformatic analysis of sequenced
      genomes indicates that homologs to shell protein genes are widespread among
      bacteria and suggests that the shell proteins are capable of encapsulating
      diverse enzymes. The carboxysome is a bacterial microcompartment that enhances
      CO(2) fixation in cyanobacteria and some chemoautotrophs by sequestering ribulose
      1,5-bisphosphate carboxylase/oxygenase and carbonic anhydrase in the
      microcompartment shell. Here, we report the in vitro and in vivo characterization
      of CcmN, a protein of previously unknown function that is absolutely conserved in
      beta-carboxysomal gene clusters. We show that CcmN localizes to the carboxysome
      and is essential for carboxysome biogenesis. CcmN has two functionally distinct
      regions separated by a poorly conserved linker. The N-terminal portion of the
      protein is important for interaction with CcmM and, by extension, ribulose-1,5
      bisphosphate carboxylase/oxygenase and the carbonic anhydrase CcaA, whereas the C
      terminal peptide is essential for interaction with the carboxysome shell.
      Deletion of the peptide abolishes carboxysome formation, indicating that its
      interaction with the shell is an essential step in microcompartment formation.
      Peptides with similar length and sequence properties to those in CcmN can be
      bioinformatically detected in a large number of diverse proteins proposed to be
      encapsulated in functionally distinct microcompartments, suggesting that this
      peptide and its interaction with its cognate shell proteins are common features
      of microcompartment assembly.

PMID- 22461623
TI  - Functional interaction of CD154 protein with alpha5beta1 integrin is totally
      independent from its binding to alphaIIbbeta3 integrin and CD40 molecules.
AB  - In addition to its classical CD40 receptor, CD154 also binds to alphaIIbbeta3,
      alpha5beta1, and alphaMbeta2 integrins. Binding of CD154 to these receptors seems
      to play a key role in the pathogenic processes of chronic inflammation. This
      investigation was aimed at analyzing the functional interaction of CD154 with
      CD40, alphaIIbbeta3, and alpha5beta1 receptors. We found that the binding
      affinity of CD154 for alphaIIbbeta3 is ~4-fold higher than for alpha5beta1. We
      also describe the generation of sCD154 mutants that lost their ability to bind
      CD40 or alphaIIbbeta3 and show that CD154 residues involved in its binding to
      CD40 or alphaIIbbeta3 are distinct from those implicated in its interaction to
      alpha5beta1, suggesting that sCD154 may bind simultaneously to different
      receptors. Indeed, sCD154 can bind simultaneously to CD40 and alpha5beta1 and
      biologically activate human monocytic U937 cells expressing both receptors. The
      simultaneous engagement of CD40 and alpha5beta1 activates the mitogen-activated
      protein kinases, p38, and extracellular signal-related kinases 1/2 and synergizes
      in the release of inflammatory mediators MMP-2 and -9, suggesting a cross-talk
      between these receptors.

PMID- 22461624
TI  - p53-induced gene 3 mediates cell death induced by glutathione peroxidase 3.
AB  - Expression of glutathione peroxidase 3 (GPx3) is down-regulated in a variety of
      human malignancies. Both methylation and deletion of GPx3 gene underlie the
      alterations of GPx3 expression in prostate cancer. A strong correlation between
      the down-regulation of GPx3 expression and progression of prostate cancer and the
      suppression of prostate cancer xenografts in SCID mice by forced expression of
      GPx3 suggests a tumor suppression role of GPx3 in prostate cancer. However, the
      mechanism of GPx3-mediated tumor suppression remains unclear. In this report,
      GPx3 was found to interact directly with p53-induced gene 3 (PIG3). Forced
      overexpression of GPx3 in prostate cancer cell lines DU145 and PC3 as well as
      immortalized prostate epithelial cells RWPE-1 increased apoptotic cell death.
      Expression of GPx3(x73c), a peroxidase-negative OPAL codon mutant, in DU145 and
      PC3 cells also increased cell death. The induced expression of GPx3 in DU145 and
      PC3 cells resulted in an increase in reactive oxygen species and caspase-3
      activity. These activities were abrogated by either knocking down PIG3 or
      mutating the PIG3 binding motif in GPx3 or binding interference from a peptide
      corresponding to PIG3 binding motif in GPx3. In addition, UV-treated RWPE-1 cells
      underwent apoptotic death, which was partially prevented by knocking down GPx3 or
      PIG3, suggesting that GPx3-PIG3 signaling is critical for UV-induced apoptosis.
      Taken together, these results reveal a novel signaling pathway of GPx3-PIG3 in
      the regulation of cell death in prostate cancer.

PMID- 22461625
TI  - Targeted deletion of LPA5 identifies novel roles for lysophosphatidic acid
      signaling in development of neuropathic pain.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid that serves as an extracellular
      signaling molecule acting through cognate G protein-coupled receptors designated
      LPA(1-6) that mediate a wide range of both normal and pathological effects.
      Previously, LPA(1), a G(alphai)-coupled receptor (which also couples to other
      G(alpha) proteins) to reduce cAMP, was shown to be essential for the initiation
      of neuropathic pain in the partial sciatic nerve ligation (PSNL) mouse model.
      Subsequent gene expression studies identified LPA(5), a G(alpha12/13)- and G(q)
      coupled receptor that increases cAMP, in a subset of dorsal root ganglion neurons
      and also within neurons of the spinal cord dorsal horn in a pattern
      complementing, yet distinct from LPA(1), suggesting its possible involvement in
      neuropathic pain. We therefore generated an Lpar5 null mutant by targeted
      deletion followed by PSNL challenge. Homozygous null mutants did not show obvious
      base-line phenotypic defects. However, following PSNL, LPA(5)-deficient mice were
      protected from developing neuropathic pain. They also showed reduced
      phosphorylated cAMP response element-binding protein expression within neurons of
      the dorsal horn despite continued up-regulation of the characteristic pain
      related markers Caalpha(2)delta(1) and glial fibrillary acidic protein, results
      that were distinct from those previously observed for LPA(1) deletion. These data
      expand the influences of LPA signaling in neuropathic pain through a second LPA
      receptor subtype, LPA(5), involving a mechanistically distinct downstream
      signaling pathway compared with LPA(1).

PMID- 22461626
TI  - C-terminal acidic cluster is involved in Ca2+-induced regulation of human
      transient receptor potential ankyrin 1 channel.
AB  - The transient receptor potential ankyrin 1 (TRPA1) channel is a Ca(2+)-permeable
      cation channel whose activation results from a complex synergy between distinct
      activation sites, one of which is especially important for determining its
      sensitivity to chemical, voltage and cold stimuli. From the cytoplasmic side,
      TRPA1 is critically regulated by Ca(2+) ions, and this mechanism represents a
      self-modulating feedback loop that first augments and then inhibits the initial
      activation. We investigated the contribution of the cluster of acidic residues in
      the distal C terminus of TRPA1 in these processes using mutagenesis, whole cell
      electrophysiology, and molecular dynamics simulations and found that the
      neutralization of four conserved residues, namely Glu(1077) and Asp(1080)
      Asp(1082) in human TRPA1, had strong effects on the Ca(2+)- and voltage-dependent
      potentiation and/or inactivation of agonist-induced responses. The surprising
      finding was that truncation of the C terminus by only 20 residues selectively
      slowed down the Ca(2+)-dependent inactivation 2.9-fold without affecting other
      functional parameters. Our findings identify the conserved acidic motif in the C
      terminus that is actively involved in TRPA1 regulation by Ca(2+).

PMID- 22461627
TI  - Loss of T regulatory cell suppression following signaling through glucocorticoid
      induced tumor necrosis receptor (GITR) is dependent on c-Jun N-terminal kinase
      activation.
AB  - Naturally occurring Foxp3(+)CD4(+)CD25(+) T regulatory cell (nTreg)-mediated
      suppression of lung allergic responses is abrogated following ligation of
      glucocorticoid-induced tumor necrosis receptor (GITR) family-related protein. In
      vitro stimulation of nTregs with GITR ligand increased phosphorylation of c-Jun N
      terminal kinase (JNK) but not extracellular signal-regulated protein kinase (ERK)
      or p38 MAPK. SP600125, a known JNK inhibitor, prevented GITR-mediated
      phosphorylation of JNK. Activation of JNK was associated with increases in the
      upstream mitogen-activated protein kinase kinase 7 (MKK7) and the downstream
      transcription factor NF-kappabeta. Phosphorylated c-Jun (p-c-Jun), indicative of
      the activation of JNK, was detected in the immunoprecipitates of nTregs from wild
      type but not JNK- or GITR-deficient mice. Treatment with an inhibitor of JNK
      phosphorylation resulted in complete reversal of all GITR-induced changes in
      nTreg phenotype and function, with full restoration of suppression of in vivo
      lung allergic responses and in vitro proliferation of activated CD4(+)CD25(-) T
      cells. Thus, regulation of JNK phosphorylation plays a central role in T
      regulatory cell function with therapeutic implications for the treatment of
      asthma and autoimmune diseases.

PMID- 22461628
TI  - Post-translational modifications regulate assembly of early spindle orientation
      complex in yeast.
AB  - Mitosis begins with the tethering of chromosomes to the mitotic spindle and their
      orientation perpendicular to the axis of cell division. In budding yeast, mitotic
      spindle orientation and the subsequent chromosome segregation are two independent
      processes. Early spindle orientation is driven by the actin-bound myosin Myo2p,
      which interacts with the adapter Kar9p. The latter also binds to microtubule
      associated Bim1p, thereby connecting both types of cytoskeleton. This study
      focuses on the interaction between Kar9p and Bim1p and its regulation. We solved
      the crystal structure of the previously reported Kar9p-binding motif of Bim1p and
      identified a second, novel Kar9p interaction domain. We further show that two
      independent post-translational modification events regulate their interaction.
      Whereas Kar9p sumoylation is required for efficient complex formation with Bim1p,
      Aurora B/Ipl1p-dependent phosphorylation of Bim1p down-regulates their
      interaction. The observed effects of these modifications allow us to propose a
      novel regulatory framework for the assembly and disassembly of the early spindle
      orientation complex.

PMID- 22461629
TI  - Small amphipathic molecules modulate secondary structure and amyloid fibril
      forming kinetics of Alzheimer disease peptide Abeta(1-42).
AB  - Amyloid fibril formation is associated with a number of debilitating systemic and
      neurodegenerative diseases. One of the most prominent is Alzheimer disease in
      which aggregation and deposition of the Abeta peptide occur. Abeta is widely
      considered to mediate the extensive neuronal loss observed in this disease
      through the formation of soluble oligomeric species, with the final fibrillar end
      product of the aggregation process being relatively inert. Factors that influence
      the aggregation of these amyloid-forming proteins are therefore very important.
      We have screened a library of 96 amphipathic molecules for effects on Abeta(1-42)
      aggregation and self-association. We find, using thioflavin T fluorescence and
      electron microscopy assays, that 30 of the molecules inhibit the aggregation
      process, whereas 36 activate fibril formation. Several activators and inhibitors
      were subjected to further analysis using analytical ultracentrifugation and
      circular dichroism. Activators typically display a 1:10 peptide:detergent
      stoichiometry for maximal activation, whereas the inhibitors are effective at a
      1:1 stoichiometry. Analytical ultracentrifugation and circular dichroism
      experiments show that activators promote a mixture of unfolded and beta-sheet
      structures and rapidly form large aggregates, whereas inhibitors induce alpha
      helical structures that form stable dimeric/trimeric oligomers. The results
      suggest that Abeta(1-42) contains at least one small molecule binding site, which
      modulates the secondary structure and aggregation processes. Further studies of
      the binding of these compounds to Abeta may provide insight for developing
      therapeutic strategies aimed at stabilizing Abeta in a favorable conformation.

PMID- 22461630
TI  - Trans-cellular propagation of Tau aggregation by fibrillar species.
AB  - Aggregation of the microtubule associated protein Tau is associated with several
      neurodegenerative disorders, including Alzheimer disease and frontotemporal
      dementia. In Alzheimer disease, Tau pathology spreads progressively throughout
      the brain, possibly along existing neural networks. However, it is still unclear
      how the propagation of Tau misfolding occurs. Intriguingly, in animal models,
      vaccine-based therapies have reduced Tau and synuclein pathology by uncertain
      mechanisms, given that these proteins are intracellular. We have previously
      speculated that trans-cellular propagation of misfolding could be mediated by a
      process similar to prion pathogenesis, in which fibrillar Tau aggregates spread
      pathology from cell to cell. However, there has been little evidence to
      demonstrate true trans-cellular propagation of Tau misfolding, in which Tau
      aggregates from one cell directly contact Tau protein in the recipient cell to
      trigger further aggregation. Here we have observed that intracellular Tau fibrils
      are directly released into the medium and then taken up by co-cultured cells.
      Internalized Tau aggregates induce fibrillization of intracellular Tau in these
      naive recipient cells via direct protein-protein contact that we demonstrate
      using FRET. Tau aggregation can be amplified across several generations of cells.
      An anti-Tau monoclonal antibody blocks Tau aggregate propagation by trapping
      fibrils in the extracellular space and preventing their uptake. Thus, propagation
      of Tau protein misfolding among cells can be mediated by release and subsequent
      uptake of fibrils that directly contact native protein in recipient cells. These
      results support the model of aggregate propagation by templated conformational
      change and suggest a mechanism for vaccine-based therapies in neurodegenerative
      diseases.

PMID- 22461631
TI  - Familial Alzheimer disease presenilin-1 mutations alter the active site
      conformation of gamma-secretase.
AB  - Presenilin-1 (PS1) is the catalytic subunit of gamma-secretase, and mutations in
      this protein cause familial Alzheimer Disease (FAD). However, little is known
      about how these mutations affect the active site of gamma-secretase. Here, we
      show that PS1 mutations alter the S2 subsite within the active site of gamma
      secretase using a multiple photoaffinity probe approach called "photophore
      walking." Moreover, we developed a unique in vitro assay with a biotinylated
      recombinant Notch1 substrate and demonstrated that PS1 FAD mutations directly and
      significantly reduced gamma-secretase activity for Notch1 cleavage. Substitution
      of the Notch Cys-1752 residue, which interacts with the S2 subsite, with Val,
      Met, or Ile has little effect on wild-type PS1 but leads to more efficient
      substrates for mutant PS1s. This study indicates that alteration of this S2
      subsite plays an important role in determining the activity and specificity of
      gamma-secretase for APP and Notch1 processing, which provides structural basis
      and insights on how certain PS1 FAD mutations lead to AD pathogenesis.

PMID- 22461632
TI  - Expression in drosophila of tandem amyloid beta peptides provides insights into
      links between aggregation and neurotoxicity.
AB  - The generation and subsequent aggregation of amyloid beta (Abeta) peptides play a
      crucial initiating role in the pathogenesis of Alzheimer disease (AD). The two
      main isoforms of these peptides have 40 (Abeta(40)) or 42 residues (Abeta(42)),
      the latter having a higher propensity to aggregate in vitro and being the main
      component of the plaques observed in vivo in AD patients. We have designed a
      series of tandem dimeric constructs of these Abeta peptides to probe the manner
      in which changes in the aggregation kinetics of Abeta affect its deposition and
      toxicity in a Drosophila melanogaster model system. The levels of insoluble
      aggregates were found to be substantially elevated in flies expressing the tandem
      constructs of both Abeta(40) and Abeta(42) compared with the equivalent monomeric
      peptides, consistent with the higher effective concentration, and hence increased
      aggregation rate, of the peptides in the tandem repeat. A unique feature of the
      Abeta(42) constructs, however, is the appearance of high levels of soluble
      oligomeric aggregates and a corresponding dramatic increase in their in vivo
      toxicity. The toxic nature of the Abeta(42) peptide in vivo can therefore be
      attributed to the higher kinetic stability of the oligomeric intermediate states
      that it populates relative to those of Abeta(40) rather than simply to its higher
      rate of aggregation.

PMID- 22461634
TI  - Infiltration of a mixture of different immune cells may be related to molecular
      profile of differentiated thyroid cancer.

PMID- 22461633
TI  - Serum calcium-decreasing factor, caldecrin, inhibits receptor activator of NF
      kappaB ligand (RANKL)-mediated Ca2+ signaling and actin ring formation in mature
      osteoclasts via suppression of Src signaling pathway.
AB  - Osteoclasts are essential for bone dynamics and calcium homeostasis. Recently, we
      reported that serum calcium-decreasing factor, caldecrin, which is a secretory
      type serine protease isolated from the pancreas, inhibits osteoclast
      differentiation by suppression of NFATc1 activity regardless of its own protease
      activity (Hasegawa, H., Kido, S., Tomomura, M., Fujimoto, K., Ohi, M., Kiyomura,
      M., Kanegae, H., Inaba, A., Sakagami, H., and Tomomura, A. (2010) Serum calcium
      decreasing factor, caldecrin, inhibits osteoclast differentiation by suppression
      of NFATc1 activity. J. Biol. Chem. 285, 25448-25457). Here, we investigated the
      effects of caldecrin on the function of mature osteoclasts by treatment with
      receptor activator of NF-kappaB ligand (RANKL). Caldecrin inhibited the RANKL
      stimulated bone resorptive activity of mature osteoclasts. Furthermore, caldecrin
      inhibited RANKL-mediated sealing actin ring formation, which is associated with
      RANKL-evoked Ca(2+) entry through transient receptor potential vanilloid channel
      4. The inhibitors of phospholipase Cgamma, Syk, and c-Src suppressed RANKL-evoked
      Ca(2+) entry and actin ring formation of mature osteoclasts. Interestingly,
      caldecrin significantly inhibited RANKL-stimulated phosphorylation of c-Src, Syk,
      phospholipase Cgamma1 and Cgamma2, SLP-76, and Pyk2 but not that of ERK, JNK, or
      Akt. Caldecrin inhibited RANKL-stimulated c-Src kinase activity and c-Src.Syk
      association. These results suggest that caldecrin inhibits RANKL-stimulated
      calcium signaling activation and cytoskeletal organization by suppression of the
      c-Src.Syk pathway, which may in turn reduce the bone resorptive activity of
      mature osteoclasts. Thus, caldecrin is capable of acting as a negative regulator
      of osteoclastogenesis and osteoclast function of bone resorption.

PMID- 22461635
TI  - PRKAR1A gene analysis and protein kinase A activity in endometrial tumors.
AB  - PRKAR1A codes for the type 1a regulatory subunit (RIalpha) of the cAMP-dependent
      protein kinase A (PKA), an enzyme with an important role in cell cycle regulation
      and proliferation. PKA dysregulation has been found in various tumors, and
      PRKAR1A-inactivating mutations have been reported in mostly endocrine neoplasias.
      In this study, we investigated PKA activity and the PRKAR1A gene in normal and
      tumor endometrium. Specimens were collected from 31 patients with endometrial
      cancer. We used as controls 41 samples of endometrium that were collected from
      surrounding normal tissues or from women undergoing gynecological operations for
      other reasons. In all samples, we sequenced the PRKAR1A-coding sequence and
      studied PKA subunit expression; we also determined PKA activity and cAMP binding.
      PRKAR1A mutations were not found. However, PKA regulatory subunit protein levels,
      both RIalpha and those of regulatory subunit type 2b (RIIbeta), were lower in
      tumor samples; cAMP binding was also lower in tumors compared with normal
      endometrium (P<0.01). Free PKA activity was higher in tumor samples compared with
      that of control tissue (P<0.01). There are significant PKA enzymatic
      abnormalities in tumors of the endometrium compared with surrounding normal
      tissue; as these were not due to PRKAR1A mutations, other mechanisms affecting
      PKA function ought to be explored.

PMID- 22461636
TI  - Winning the war: science parkour.

PMID- 22461637
TI  - Intratumor heterogeneity: seeing the wood for the trees.
AB  - Most advanced solid tumors remain incurable, with resistance to chemotherapeutics
      and targeted therapies a common cause of poor clinical outcome. Intratumor
      heterogeneity may contribute to this failure by initiating phenotypic diversity
      enabling drug resistance to emerge and by introducing tumor sampling bias.
      Envisaging tumor growth as a Darwinian tree with the trunk representing
      ubiquitous mutations and the branches representing heterogeneous mutations may
      help in drug discovery and the development of predictive biomarkers of drug
      response.

PMID- 22461638
TI  - Raising the bar: the curative potential of human cancer immunotherapy.
AB  - Immunotherapy with interleukin-2 can cure 5 to 10% of patients with metastatic
      melanoma and renal cancer. Recent adoptive cell transfer (ACT) immunotherapies
      have improved cure rates in metastatic melanoma to 20 to 40%. Genetic engineering
      of T cells to express conventional alpha/beta T cell receptors or antibody-based
      chimeric antigen receptors provides an opportunity to extend ACT to patients with
      common epithelial cancers.

PMID- 22461639
TI  - Pluripotent stem cell-based cancer therapy: promise and challenges.
AB  - The development of induced pluripotent stem cell (iPSC) technology has generated
      enthusiasm about the therapeutic potential of these cells for treating a variety
      of diseases. However, the evidence that they actually will be clinically useful
      is limited. Here, we discuss the potential therapeutic applications of iPSCs for
      treating cancer and other diseases and highlight the current barriers restricting
      their use.

PMID- 22461640
TI  - Anti-invasive adjuvant therapy with imipramine blue enhances chemotherapeutic
      efficacy against glioma.
AB  - The invasive nature of glioblastoma (GBM) represents a major clinical challenge
      contributing to poor outcomes. Invasion of GBM into healthy tissue restricts
      chemotherapeutic access and complicates surgical resection. Here, we test the
      hypothesis that an effective anti-invasive agent can "contain" GBM and increase
      the efficacy of chemotherapy. We report a new anti-invasive small molecule,
      Imipramine Blue (IB), which inhibits invasion of glioma in vitro when tested
      against several models. IB inhibits NADPH (reduced form of nicotinamide adenine
      dinucleotide phosphate) oxidase-mediated reactive oxygen species generation and
      alters expression of actin regulatory elements. In vivo, liposomal IB (nano-IB)
      halts invasion of glioma, leading to a more compact tumor in an aggressively
      invasive RT2 syngeneic astrocytoma rodent model. When nano-IB therapy was
      followed by liposomal doxorubicin (nano-DXR) chemotherapy, the combination
      therapy prolonged survival compared to nano-IB or nano-DXR alone. Our data
      demonstrate that nano-IB-mediated containment of diffuse glioma enhanced the
      efficacy of nano-DXR chemotherapy, demonstrating the promise of an anti-invasive
      compound as an adjuvant treatment for glioma.

PMID- 22461641
TI  - Colocalization of inflammatory response with B7-h1 expression in human
      melanocytic lesions supports an adaptive resistance mechanism of immune escape.
AB  - Although many human cancers such as melanoma express tumor antigens recognized by
      T cells, host immune responses often fail to control tumor growth for as yet
      unexplained reasons. Here, we found a strong association between melanocyte
      expression of B7-H1 (PD-L1), an immune-inhibitory molecule, and the presence of
      tumor-infiltrating lymphocytes (TILs) in human melanocytic lesions: 98% of B7
      H1(+) tumors were associated with TILs compared with only 28% of B7-H1(-) tumors.
      Indeed, B7-H1(+) melanocytes were almost always localized immediately adjacent to
      TILs. B7-H1/TIL colocalization was identified not only in melanomas but also in
      inflamed benign nevi, indicating that B7-H1 expression may represent a host
      response to tissue inflammation. Interferon-gamma, a primary inducer of B7-H1
      expression, was detected at the interface of B7-H1(+) tumors and TILs, whereas
      none was found in B7-H1(-) tumors. Therefore, TILs may actually trigger their own
      inhibition by secreting cytokines that drive tumor B7-H1 expression. Consistent
      with this hypothesis, overall survival of patients with B7-H1(+) metastatic
      melanoma was significantly prolonged compared with that of patients with B7-H1(-)
      metastatic melanoma. Therefore, induction of the B7-H1/PD-1 pathway may represent
      an adaptive immune resistance mechanism exerted by tumor cells in response to
      endogenous antitumor activity and may explain how melanomas escape immune
      destruction despite endogenous antitumor immune responses. These observations
      suggest that therapies that block this pathway may benefit patients with B7-H1(+)
      tumors.

PMID- 22461642
TI  - Targeting of AML1-ETO in t(8;21) leukemia by oridonin generates a tumor
      suppressor-like protein.
AB  - Nearly 60% of acute myeloid leukemia (AML) patients with the t(8;21)(q22;q22)
      translocation fail to achieve long-term disease-free survival. Our previous
      studies demonstrated that oridonin selectively induces apoptosis of t(8;21)
      leukemia cells and causes cleavage of AML1-ETO oncoprotein resulting from
      t(8;21), but the underlying mechanisms remain unclear. We show that oridonin
      interacted with glutathione and thioredoxin/thioredoxin reductase to increase
      intracellular reactive oxygen species, which in turn activated caspase-3 in
      t(8;21) cells. Moreover, oridonin bound AML1-ETO, directing the enzymatic
      cleavage at aspartic acid 188 via caspase-3 to generate a truncated AML1-ETO
      (DeltaAML1-ETO) and preventing the protein from further proteolysis. DeltaAML1
      ETO interacted with AML1-ETO and interfered with the trans-regulatory functions
      of remaining AML1-ETO oncoprotein, thus acting as a tumor suppressor that
      mediates the anti-leukemia effect of oridonin. Furthermore, oridonin inhibited
      the activity of c-Kit(+) leukemia-initiating cells. Therefore, oridonin is a
      potential lead compound for molecular target-based therapy of leukemia.

PMID- 22461643
TI  - Improving treatment of HER2-positive cancers: opportunities and challenges.
AB  - Amplification of the ERBB2 gene, which encodes human epidermal growth factor
      receptor 2 (HER2), causes the overexpression of a major proliferative driver for
      a subset of breast and gastric cancers. Treatments for patients with HER2
      positive cancer include the monoclonal antibody trastuzumab and, in the case of
      metastatic breast cancer, the tyrosine kinase inhibitor lapatinib. Despite
      significant improvement in patient outcome as a result of these therapies,
      challenges remain. This Review focuses on proposed mechanisms of action and
      resistance in the context of potential new therapeutic options. Therapeutic
      approaches currently in development likely will yield additional clinically
      meaningful improvements for patients with HER2-positive cancer.

PMID- 22461644
TI  - Beyond PSA: the next generation of prostate cancer biomarkers.
AB  - Since the introduction of serum prostate-specific antigen (PSA) screening 25
      years ago, prostate cancer diagnosis and management have been guided by this
      biomarker. Yet, PSA has proven controversial as a screening assay owing to
      several inherent limitations. The next wave of prostate cancer biomarkers has
      emerged, introducing new assays in serum and urine that may supplement or, in
      time, replace PSA because of their higher cancer specificity. This expanding
      universe of biomarkers has been facilitated, in large part, by new genomic
      technologies that have enabled an unbiased look at cancer biology. Such efforts
      have produced several notable success stories that involve rapidly moving
      biomarkers from the bench to the clinic. However, biomarker research has centered
      on disease diagnostics, rather than prognosis and prediction, which would address
      disease management. The development of biomarkers to stratify risk of prostate
      cancer aggressiveness at the time of screening remains the greatest unmet
      clinical need in prostate cancer. We review the current state of prostate cancer
      biomarker research, including the PSA revolution, its impact on early cancer
      detection, the recent advances in biomarker discovery, and the future efforts
      that promise to improve clinical management of this disease.

PMID- 22461646
TI  - Yogi Berra, Forrest Gump, and the discovery of Listeria actin comet tails.
AB  - In 1988, eminent cell biologist Lew Tilney and newly appointed Assistant
      Professor of Microbiology Dan Portnoy met at a picnic and initiated a
      collaboration that led to a groundbreaking paper published in Journal of Cell
      Biology entitled "Actin filaments and the growth, movement, and spread of the
      intracellular bacterial parasite, Listeria monocytogenes." The paper has been
      cited more than 800 times, the most of any publication in the careers of both
      investigators. Using an electron microscope from the Sputnik era, they assembled
      a stunning collection of micrographs that illustrated how L. monocytogenes enters
      the host cell and exploits a host system of actin-based motility to move within
      cells and into neighboring cells without leaving the host cell cytosol. This
      research captured the imagination of cell biologists and microbiologists alike
      and led to novel insights into cytoskeletal dynamics. Here, Portnoy provides a
      retrospective that shares text from the original submission that was deleted at
      the time of publication, along with reviewers' comments ranging from "It is
      really just a show and tell paper and doesn';t have any meat" to "the finding
      will have major impact in cell biology and in medicine. Potentially, the paper
      will be a classic."

PMID- 22461647
TI  - Prolonged sampling of spontaneous sputum improves sensitivity of hypermethylation
      analysis for lung cancer.
AB  - AIMS: The adequacy of lung cancer diagnosis with sputum cytology depends on
      duration of sputum sampling. The aim of this methodological study was to
      determine whether the hypermethylation detection rate of RASSF1A, adenomatous
      polyposis coli (APC) and cytoglobin (CYGB) is influenced by the duration of
      sputum collection. METHODS: Prospective sputum samples were collected from 53
      lung cancer patients and 47 chronic obstructive pulmonary disease patients as
      controls. Subjects collected spontaneous sputum at home during nine consecutive
      days in three canisters I, II and III (ie, days 1-3, days 4-6, days 7-9,
      respectively). Quantitative methylation-specific PCR was performed to assess gene
      promoter methylation status of RASSF1A, APC and CYGB. RESULTS: Analysis of each
      canister separately showed hypermethylation of RASSF1A, APC and/or CYGB in
      samples I, II and III, in 43%, 40% and 47% of cases, respectively. In control
      samples, these numbers were 4%, 2% and 4%, respectively. Cumulative analysis for
      days 1-6 and days 1-9 revealed an increase in sensitivity to 53% and 64%, and
      specificity of 94% and 91%, respectively. CONCLUSION: Sputum collected over
      multiple successive days results in a gain in sensitivity for the detection of
      lung cancer, at the expense of a small loss in specificity. Condensed abstract
      Assessment of hypermethylation sensitivity of biomarkers in sputum collected over
      a prolonged period for the detection of lung cancer resulted in a promising gain
      in sensitivity, at the expense of a small loss in specificity.

PMID- 22461645
TI  - Applying what we know to accelerate cancer prevention.
AB  - More than half of the cancer occurring today is preventable by applying knowledge
      that we already have. Tobacco, obesity, and physical inactivity are the
      modifiable causes of cancer that generate the most disease. Cancer burden can be
      reduced by alterations in individual and population behaviors and by public
      health efforts as long as these changes are driven by sound scientific knowledge
      and social commitment to change. The obstacles to these efforts are societal and
      arise from the organization of institutions, including academia, and in the
      habits of daily life. To achieve maximal possible cancer prevention, we will need
      better ways to implement what we know and improved infrastructure that will
      better incentivize and support transdisciplinary, multilevel research and
      successful intervention.

PMID- 22461648
TI  - KRAS mutational status of endoscopic biopsies matches resection specimens.
AB  - AIMS: This study was performed to determine systematically whether KRAS
      mutational analysis in biopsy tissue is a reliable indicator of KRAS status in
      subsequent corresponding resection specimens. METHODS: 30 colorectal cancer (CRC)
      patients with biopsy and corresponding subsequent surgical resection specimens
      were studied. KRAS mutational analysis was performed on each biopsy sample as
      well as two separate samples from each resection specimen by PCR and Sanger
      sequencing. RESULTS: Overall, KRAS mutations were identified in 12/30 (40%) of
      the tumours. There was 100% correlation between biopsy and resection specimens
      regarding the presence or absence of KRAS mutations. In fact, the same point
      mutation was identified in both biopsy and corresponding resection specimens in
      12/12 (100%) cases. In addition, in two cases, there were two different point
      mutations detected within the same biopsy specimen. CONCLUSION: This study shows
      perfect correlation between KRAS mutation status in biopsy and resection
      specimens from an individual patient, and suggests that biopsy material is
      adequate for KRAS mutational analysis in CRC patients.

PMID- 22461649
TI  - Quality control by tissue microarray in immunohistochemistry.
AB  - AIMS: An external positive control section is included in each
      immunohistochemical analysis as a well recognised and validated technique for
      standardising results. The method is time-consuming and expensive. On the
      contrary, internal controls are warranted and inexpensive, but their use is only
      feasible in selected diagnoses. The aim of this work is to show how the method of
      the authors allows improving the interpretation and cuts costs in the
      immunohistochemical analysis of bone marrow specimens. METHODS: A paraffin
      embedded tonsil tissue cylinder was sampled from a donor block using an automated
      sampler and included as an 'internal control' together with a bone marrow biopsy
      in a recipient block, avoiding the use of external tonsil tissue control. To
      validate this technique, the authors compared the quality of
      immunohistochemistry, the workload and costs with routine external control in 50
      consecutive bone marrow biopsies. RESULTS: Processing simultaneously the sample
      and the tissue control in the same block, 60 external positive control tests were
      spared. Only a few minutes were taken for the preparation of the recipient
      blocks, and no particular technical skill was required. Considering that the
      volume of antibodies used for the analysis of each sample was not increased, a
      considerable amount of the disposable material was saved. The workload of
      technicians was decreased and some potential technical bias was avoided. The time
      required for pathologists to interpret the slides was also reduced. CONCLUSIONS:
      In conclusion, this seems to be a feasible, cost-cutting and quality-improving
      technique, not limited to haematopathology but potentially extensible to other
      fields of pathology.

PMID- 22461650
TI  - Positive JAK2-V617F leading to diagnosis of Gaucher's disease.

PMID- 22461651
TI  - A170P mutation in SHOX gene in a patient not presenting with Madelung deformity.
AB  - Idiopathic short stature is a multifactorial disease caused by defects in several
      genes. Among them, short stature homeobox-containing gene (SHOX) mutations have
      an incidence of 2%-15% within the idiopathic short population. The authors report
      a patient with moderate intellectual disability, short stature and no other
      radiological traits referred for subtelomeric screening. MLPA and sequencing
      results showed a heterozygous mutation in SHOX gene (A170P). This mutation has
      been described to fully cosegregate with Madelung deformity in patients affected
      with Leri-Weill dyschondrosteosis and Langer mesomelic dysplasia. The authors
      report the first case of idiopathic short stature due to the A170P mutation in a
      patient without any radiological trait. The A170P mutation is the most prevalent
      mutation in the Spanish gypsy population affected with short stature disorders.
      The authors strongly recommend SHOX screening for deletions, duplications and
      point mutations in patients affected with short stature although they do not
      present any radiological traits.

PMID- 22461652
TI  - Tubular carcinoids of the appendix: the CK7/CK20 immunophenotype can be a
      diagnostic pitfall.
AB  - AIMS: Tubular carcinoid is a rare variant of appendiceal well-differentiated
      neuroendocrine tumour. Although considered benign lesions, the small infiltrating
      tubules that characterise the tumour may raise concern for metastatic
      adenocarcinoma. To our knowledge, the cytokeratin 7 (CK7)/cytokeratin 20 (CK20)
      expression profile of these neoplasms remains unexplored. METHODS: The authors
      characterised the CK7/CK20 immunophenotype and Ki-67 expression of the eight
      available tubular carcinoids seen at their institution from 1991 to 2011.
      RESULTS: CK7 and CK20 staining was variable, ranging from none to focal staining
      for either or both CK7 and CK20, to diffuse expression of CK7 or CK20.
      CONCLUSIONS: The CK7/CK20 expression profile is of limited value when the
      differential diagnosis includes primary tubular carcinoid and well-differentiated
      metastatic adenocarcinoma. In such cases, careful attention to the location of
      the neoplasm, mitotic count and presence or absence of an associated classic
      carcinoid component are more useful for arriving at the correct diagnosis.

PMID- 22461653
TI  - Infiltrative epitheliosis of the breast.

PMID- 22461654
TI  - First case of Hb Fontainebleau with sickle haemoglobin and other non-deletional
      alpha gene variants identified in neonates during newborn screening for sickle
      cell disorders.
AB  - OBJECTIVE: To evaluate the significance of non-deletional alpha gene variants
      identified in neonates during newborn screening for sickle cell disorders.
      METHODS: 1534 newborn babies were screened in the last 2 years for sickle cell
      disease using a targeted screening approach. Investigations included a complete
      blood count, high performance liquid chromatography analysis, cellulose acetate
      electrophoresis (pH 8.9), heat stability test, restriction digestion and
      Amplified Refractory Mutation System for confirmation of sickle haemoglobin (Hb
      S), alpha genotyping by multiplex PCR and DNA sequencing. RESULTS: Three non
      deletional alpha gene variants, Hb Fontainebleau, Hb O Indonesia and Hb Koya
      Dora, were identified in heterozygous condition in newborns. This is the first
      report of Hb Fontainebleau in association with Hb S. The baby had anaemia at
      birth (Hb 11.4 g/dl) with no cyanosis, icterus or need for transfusion. She had
      occipital encephalocoele and was operated on day 24 to remove the mass. The baby
      diagnosed with Hb O Indonesia in combination with Hb S also had a low haemoglobin
      level of 12.7 g/dl. CONCLUSION: Newborn screening for sickle cell disorders also
      enabled us to identify three alpha globin chain variants. Two babies who
      inherited Hb Fontainebleau and Hb O Indonesia along with Hb S had reduced Hb
      levels at birth and need to be followed up.

PMID- 22461655
TI  - Significance of acquired diverticular disease of the vermiform appendix: a marker
      of regional neoplasms?
AB  - AIM: To assess the prevalence of acquired diverticulum of the appendix (DA),
      including incipient forms and its possible significance as a marker of
      local/regional neoplasms. MATERIALS AND METHODS: The pathology database at
      Hvidovre Hospital was searched for appendix specimens, received between 2001 and
      2010, coded for DA or for a space-occupying lesion. Slides were reviewed to
      determine DA status and the nature of lesions possibly causing DA. RESULT: Among
      4413 appendix specimens, DA were identified in 39 (0.9%, CI 0.6% to 1.2%) cases,
      17 (43.6%, 28.0% to 59.2%) of which additionally harboured an appendiceal
      neoplasm/neoplastic precursor, whereas this figure was 1.2% (CI 0.9% to 1.6%) for
      non-DA specimens (p<0.0001). Six of the 39 DA specimens comprised incipient DA,
      three of which coexisted with appendiceal neoplasms. In addition, local/regional
      non-neoplastic lesions (six cases) and colorectal carcinomas (four cases)
      coexisted with DA. CONCLUSION: DA has significance as a putative marker of
      local/regional neoplasms. Therefore, a DA specimen proved significantly more
      likely to harbour a neoplastic growth than a non-DA counterpart. Submission for
      microscopy of the entire DA specimen, whether transmural or only incipient, and a
      comment in the pathology report on the occasional concurrence of local/regional
      neoplasms in this setting seem appropriate. The observation of DA may thus
      provide a valuable contribution in the diagnostic process.

PMID- 22461656
TI  - Expression of melanoma differentiation associated gene 5 is increased in human
      gastric mucosa infected with Helicobacter pylori.
AB  - Helicobacter pylori infection is associated with gastroduodenal diseases.
      Melanoma differentiation associated gene 5 (MDA5) plays a role in antiviral host
      defense. We investigated the effect of H pylori infection on MDA5 expression in
      human gastric mucosa. Biopsy samples from the antrum and corpus were obtained
      from 33 patients. MDA5 mRNA and protein were examined by real-time PCR and
      immunohistochemical staining. Histological gastritis was graded according to
      updated Sydney System. MDA5 mRNA was significantly increased in the antrum
      infected with H pylori. MDA5 protein positively stained in infiltrating
      mononuclear cells. MDA5 mRNA expression was significantly correlated with the
      grade of glandular atrophy (rs = 0.767) and intestinal metaplasia (rs = 0.748) in
      the corpus with H pylori infection. These results indicate that MDA5 may be
      involved in innate immune reactions against H pylori and associate with glandular
      atrophy and intestinal metaplasia in patients with H pylori infection.

PMID- 22461657
TI  - Comprehension and companionship in the emergency department as predictors of
      treatment adherence.
AB  - OBJECTIVE: Lack of adherence to recommended treatment poses major clinical and
      economic challenges for psychiatry, and requires further examination. In this
      pilot study, we aimed to prospectively investigate the association between the
      level of understanding of psychiatric emergency department (ED) discharge
      recommendations and the presence of a companion with short-term treatment
      adherence. METHOD: Sixty subjects were evaluated twice: upon ED discharge and a
      month later. Instruments included a structured questionnaire based on the
      MacArthur Competence Assessment Tool for Treatment, Mini Mental State
      Examination, and corroboration of data with the computerized hospital medical
      file. In order to control for the possibility that evaluation of the
      understanding of recommendations might positively influence adherence, the 60
      subjects were randomly assigned into 50 who were interviewed with the full survey
      tool and 10 who were not asked questions about their understanding of treatment
      and/or follow-up recommendations. RESULTS: Understanding of discharge
      recommendations and the presence of a companion enhanced adherence. CONCLUSIONS:
      This preliminary study suggests that ensuring patients' understanding of
      treatment recommendations and encouraging the company of patients are achievable,
      practical strategies that may improve adherence and thereby promote better
      outcomes.

PMID- 22461658
TI  - Impact of a psychiatric unit's daily discharge rates on emergency department
      flow.
AB  - OBJECTIVE: To investigate relationships between time spent in the emergency
      department (ED) in patients requiring admission to the psychiatric ward, the day
      of the week of presentation and the daily number of discharges from the
      psychiatric ward. METHOD: Retrospective analysis of patient flow as a function of
      day of week, time of day (a.m., p.m.), number of patients requiring admission and
      number of ward discharges over a one-year period, for all mental health related
      presentations to the ED of the Queen Elizabeth Hospital in Adelaide, South
      Australia, before their admission to the psychiatric inpatient facility. RESULTS:
      The time spent by patients in the ED waiting for admission to the psychiatric
      ward was significantly greater on weekends. There were significantly fewer
      discharges from the psychiatric ward during weekends compared with weekdays. The
      average time spent by patients in the ED requiring admission to the psychiatric
      ward for those days when there were vacant beds was 17.9 hours (SD=14.5). More
      people presented to the ED with a psychiatric diagnosis in the afternoons. There
      was a significant inverse correlation between the time spent by patients in the
      ED requiring admission to the psychiatric ward per day and the number of
      discharges from the psychiatric ward per day. CONCLUSION: These findings
      demonstrate that patient flow is significantly slower on weekends because of
      fewer discharges from the ward, leading to longer times spent in the ED before
      ward transfer. Waiting times in the ED were very substantially greater than the
      proposed 4-hour target even when vacant beds were available, raising considerable
      doubt about that target being realistic for psychiatric patients.

PMID- 22461659
TI  - Outcomes from a regular medication information programme for consumers with a
      mental illness.
AB  - OBJECTIVE: To describe the development of, and outcomes from, a medication
      information programme facilitated by trained mental health clinicians in an area
      mental health service. METHOD: A step-wise programme entailing: (a) a consumer
      led project to determine barriers faced by consumers in acquiring information
      about medication (Medicine Awareness Project:MAP); (b) the introduction of a
      weekly medication information forum (MIF) in an acute inpatient service; and (c)
      the development and roll-out of consumer and carer support materials in community
      settings. RESULTS: The MAP survey demonstrated that consumers' knowledge about
      and access to standard Consumer Medicine Information (CMI) leaflets was poor and
      that they perceived a number of barriers in obtaining balanced information about
      their medication. Nearly half of the respondents preferred information about
      medications presented in both written and verbal form. Participants in the MIF
      sessions showed an increase in positive attitudes toward their medication
      following the forums. These findings brought upon the production of a tailored,
      consumer and carer-focused resource, which has been widely distributed throughout
      Australia. CONCLUSIONS: A medication information programme can provide
      opportunities for mental health consumers and their carers to gain knowledge of
      psychotropic medications. The use of written and verbal formats enhances the
      transfer of such information.

PMID- 22461660
TI  - Retraction in part: A genomic approach to identify molecular pathways associated
      with chemotherapy resistance.

PMID- 22461661
TI  - IGF-1R/MDM2 relationship confers enhanced sensitivity to RITA in Ewing sarcoma
      cells.
AB  - Ewing sarcoma is one of the most frequent bone cancers in adolescence. Although
      multidisciplinary therapy has improved the survival rate for localized tumors, a
      critical step is the development of new drugs to improve the long-term outcome of
      recurrent and metastatic disease and to reduce side effects of conventional
      therapy. Here, we show that the small molecule reactivation of p53 and induction
      of tumor cell apoptosis (RITA, NSC652287) is highly effective in reducing growth
      and tumorigenic potential of Ewing sarcoma cell lines. These effects occur both
      in the presence of wt-p53 as well as of mutant or truncated forms of p53, or in
      its absence, suggesting the presence of additional targets in this tumor
      histotype. Further experiments provided evidence that RITA modulates an important
      oncogenic mark of these cell lines, insulin-like growth factor receptor 1 (IGF
      1R). Particularly, RITA causes downregulation of IGF-1R protein levels. MDM2
      degradative activity is involved in this phenomenon. Indeed, inhibition of MDM2
      function by genetic or pharmacologic approaches reduces RITA sensitivity of Ewing
      sarcoma cell lines. Overall, these data suggest that in the cell context of Ewing
      sarcoma, RITA may adopt additional mechanism of action besides targeting p53,
      expanding its field of application. Noteworthy, these results envisage the
      promising utilization of RITA or its derivative as a potential treatment for
      Ewing sarcomas.

PMID- 22461662
TI  - Metabolic syndrome defined by modified International Diabetes Federation criteria
      and type 2 diabetes mellitus risk: a 9-year follow-up among the aged in Finland.
AB  - The aim was to analyse the relationship between metabolic syndrome and type 2
      diabetes mellitus risk among the aged. This was a prospective population-based
      study, with a 9-year follow-up. All subjects of the municipality of Lieto in
      Finland aged >=64 in 1998-1999 with no type 2 diabetes mellitus at baseline
      (n=1117) were included. Hazard ratios for incident type 2 diabetes mellitus
      predicted by metabolic syndrome (defined by modified International Diabetes
      Federation criteria) were estimated. During the 9-year follow-up, a total of 69
      participants (6.2%) developed type 2 diabetes mellitus. After multivariable
      adjustment (age, gender, smoking, frequency of exercise, cardiovascular disease
      and low-density lipoprotein-cholesterol), type 2 diabetes mellitus (hazard ratio,
      95% confidence interval) (3.15, 1.89-5.25, p < 0.001) was more common in subjects
      with metabolic syndrome compared to subjects without it. Evaluating metabolic
      syndrome components individually, impaired fasting glucose (5.09, 2.64-9.82, p <
      0.001) and obesity (1.71, 1.05-2.97, p = 0.034) predicted a higher incidence of
      type 2 diabetes mellitus. Our findings suggest that metabolic syndrome predicts
      onset of type 2 diabetes mellitus even in late life. Impaired fasting glucose and
      obesity should be targets for primary prevention of diabetes among the aged with
      metabolic syndrome.

PMID- 22461665
TI  - Illumina sequencing technology as a method of identifying T-DNA insertion loci in
      activation-tagged Arabidopsis thaliana plants.

PMID- 22461663
TI  - Functional evaluation of a fluorescent schweinfurthin: mechanism of cytotoxicity
      and intracellular quantification.
AB  - Schweinfurthins are potent inhibitors of cancer cell growth, especially against
      human central nervous system tumor lines such as SF-295 cells. However, the
      mechanisms through which these compounds impede cell growth are not fully
      understood. In an effort to understand the basis for the effects of
      schweinfurthins, we present a fluorescent schweinfurthin, 3-deoxyschweinfurthin B
      like p-nitro-bis-stilbene (3dSB-PNBS), which displays biological activity similar
      to that of 3-deoxyschweinfurthin B (3dSB). These two schweinfurthins retain the
      unique differential activity of the natural schweinfurthins, as evidenced by the
      spindle-like morphological changes induced in SF-295 cells and the unaltered
      appearance of human lung carcinoma A549 cells. We demonstrate that incubation
      with 3dSB or 3dSB-PNBS results in cleavage of poly-ADP-ribose polymerase (PARP)
      and caspase-9, both markers of apoptosis. Coincubation of 3dSB or 3dSB-PNBS with
      the caspase-9 inhibitor (Z)-Leu-Glu(O-methyl)-His-Asp(O-methyl)
      fluoromethylketone prevents PARP cleavage. Therapeutic agents that induce
      apoptosis often activate cellular stress pathways. A marker for multiple stress
      pathways is the phosphorylation of eukaryotic initiation factor 2alpha, which is
      phosphorylated in response to 3dSB and 3dSB-PNBS treatment. Glucose-regulated
      protein 78 and protein disulfide isomerase, both endoplasmic reticulum
      chaperones, are up-regulated with schweinfurthin exposure. Using the fluorescent
      properties of 3dSB-PNBS and dimethoxyphenyl-p-nitro-bis-stilbene (DMP-PNBS), a
      control compound, we show that the intracellular levels of 3dSB-PNBS are higher
      than those of Rhodamine 123 or DMP-PNBS in SF-295 and A549 cells.

PMID- 22461666
TI  - SGT1 is induced by the potato virus X TGBp3 and enhances virus accumulation in
      Nicotiana benthamiana.

PMID- 22461667
TI  - The LysM receptor-like kinase LysM RLK1 is required to activate defense and
      abiotic-stress responses induced by overexpression of fungal chitinases in
      Arabidopsis plants.
AB  - Application of crab shell chitin or pentamer chitin oligosaccharide to
      Arabidopsis seedlings increased tolerance to salinity in wild-type but not in
      knockout mutants of the LysM Receptor-Like Kinase1 (CERK1/LysM RLK1) gene, known
      to play a critical role in signaling defense responses induced by exogenous
      chitin. Arabidopsis plants overexpressing the endochitinase chit36 and
      hexoaminidase excy1 genes from the fungus Trichoderma asperelleoides T203 showed
      increased tolerance to salinity, heavy-metal stresses, and Botrytis cinerea
      infection. Resistant lines, overexpressing fungal chitinases at different levels,
      were outcrossed to lysm rlk1 mutants. Independent homozygous hybrids lost
      resistance to biotic and abiotic stresses, despite enhanced chitinase activity.
      Expression analysis of 270 stress-related genes, including those induced by
      reactive oxygen species (ROS) and chitin, revealed constant up-regulation (at
      least twofold) of 10 genes in the chitinase-overexpressing line and an additional
      76 salt-induced genes whose expression was not elevated in the lysm rlk1 knockout
      mutant or the hybrids harboring the mutation. These findings elucidate that
      chitin-induced signaling mediated by LysM RLK1 receptor is not limited to biotic
      stress response but also encompasses abiotic-stress signaling and can be conveyed
      by ectopic expression of chitinases in plants.

PMID- 22461668
TI  - The Arabidopsis LFR gene is required for the formation of anther cell layers and
      normal expression of key regulatory genes.
AB  - The anther is the male reproductive organ in flowering plants. Although some
      genes were reported to be involved in anther development, the molecular
      mechanisms underlying the transcriptional regulation of these genes is unclear.
      lfr-2 (leaf and flower related-2), the null allele of Arabidopsis thaliana LFR
      (LEAF AND FLOWER RELATED), was male-sterile. The anthers of lfr-2 plants were
      defective in sporogenous cell formation, tapetum development, and pollen
      development. In agreement with these phenotypes, expression studies showed that
      LFR was expressed in all cell layers of the anther, and that expression was
      particularly strong in the tapetal cells and pollen grains. Quantitative RT-PCR
      analysis revealed that LFR is required for the normal transcription of some
      anther development-related genes, such as AMS, CALS5, and DYT1, MS1 and MS2, and
      ROXY2. Genetic analysis showed that SPL was epistatic to LFR while LFR was
      epistatic to DYT1. We propose that LFR may be a crucial component in the
      regulation of a genetic network that modulates anther development.

PMID- 22461670
TI  - Extensive characterizations of bacteria isolated from catheterized urine and
      stone matrices in patients with nephrolithiasis.
AB  - BACKGROUND: Urinary tract infections are generally known to be associated with
      nephrolithiasis, particularly struvite stone, in which the most common microbe
      found is urea-splitting bacterium, i.e. Proteus mirabilis. However, our
      observation indicated that it might not be the case of stone formers in Thailand.
      We therefore extensively characterized microorganisms associated with all types
      of kidney stones. METHODS: A total of 100 kidney stone formers (59 males and 41
      females) admitted for elective percutaneous nephrolithotomy were recruited and
      microorganisms isolated from catheterized urine and cortex and nidus of their
      stones were analyzed. RESULTS: From 100 stone formers recruited, 36 cases had a
      total of 45 bacterial isolates cultivated from their catheterized urine and/or
      stone matrices. Among these 36 cases, chemical analysis by Fourier-transformed
      infrared spectroscopy revealed that 8 had the previously classified 'infection
      induced stones', whereas the other 28 cases had the previously classified
      'metabolic stones'. Calcium oxalate (in either pure or mixed form) was the most
      common and found in 64 and 75% of the stone formers with and without bacterial
      isolates, respectively. Escherichia coli was the most common bacterium
      (approximately one-third of all bacterial isolates) found in urine and stone
      matrices (both nidus and periphery). Linear regression analysis showed
      significant correlation (r = 0.860, P < 0.001) between bacterial types in urine
      and stone matrices. Multidrug resistance was frequently found in these isolated
      bacteria. Moreover, urea test revealed that only 31% were urea-splitting
      bacteria, whereas the majority (69%) had negative urea test. CONCLUSIONS: Our
      data indicate that microorganisms are associated with almost all chemical types
      of kidney stones and urea-splitting bacteria are not the major causative
      microorganisms found in urine and stone matrices of the stone formers in
      Thailand. These data may lead to rethinking and a new roadmap for future research
      regarding the role of microorganisms in kidney stone formation.

PMID- 22461671
TI  - Pantoea ananatis as a cause of corneal infiltrate after rice husk injury.
AB  - We report a case of an agricultural worker presenting with corneal infiltrate
      following ocular injury with a rice husk. On examination, a superficial corneal
      foreign body was removed and sent for culture, which grew Pantoea ananatis. This
      is, to our knowledge, the first clinical case report of Pantoea ananatis causing
      corneal infiltrate.

PMID- 22461672
TI  - Wild-type MIC distributions and epidemiological cutoff values for amphotericin B,
      flucytosine, and itraconazole and Candida spp. as determined by CLSI broth
      microdilution.
AB  - Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been
      established for several Candida spp. and the newer triazoles and echinocandins
      but are not yet available for older antifungal agents, such as amphotericin B,
      flucytosine, or itraconazole. We determined species-specific ECVs for
      amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida
      spp. (30,221 strains) using isolates from 16 different laboratories in Brazil,
      Canada, Europe, and the United States, all tested by the CLSI reference
      microdilution method. The calculated 24- and 48-h ECVs expressed in MUg/ml (and
      the percentages of isolates that had MICs less than or equal to the ECV) for AMB,
      FC, and ITR, respectively, were 2 (99.8)/2 (99.2), 0.5 (94.2)/1 (91.4), and 0.12
      (95.0)/0.12 (92.9) for C. albicans; 2 (99.6)/2 (98.7), 0.5 (98.0)/0.5 (97.5), and
      2 (95.2)/4 (93.5) for C. glabrata; 2 (99.7)/2 (97.3), 0.5 (98.7)/0.5 (97.8), and
      05. (99.7)/0.5 (98.5) for C. parapsilosis; 2 (99.8)/2 (99.2), 0.5 (93.0)/1
      (90.5), and 0.5 (97.8)/0.5 (93.9) for C. tropicalis; 2 (99.3)/4 (100.0), 32
      (99.4)/32 (99.3), and 1 (99.0)/2 (100.0) for C. krusei; 2 (100.0)/4 (100.0), 0.5
      (95.3)/1 (92.9), and 0.5 (95.8)/0.5 (98.1) for C. lusitaniae; -/2 (100.0), 0.5
      (98.8)/0.5 (97.7), and 0.25 (97.6)/0.25 (96.9) for C. dubliniensis; and 2
      (100.0)/2 (100.0), 1 (92.7)/-, and 1 (100.0)/2 (100.0) for C. guilliermondii. In
      the absence of species-specific CBP values, these wild-type (WT) MIC
      distributions and ECVs will be useful for monitoring the emergence of reduced
      susceptibility to these well-established antifungal agents.

PMID- 22461673
TI  - Comparison of swab and sponge methodologies for identification of Acinetobacter
      baumannii from the hospital environment.
AB  - The ideal sampling method for identification of Acinetobacter baumannii from the
      health care environment is unknown. In this study, we sampled 145 surfaces in the
      rooms of patients with known A. baumannii colonization/infection, comparing two
      methods: swab and sponge. The sensitivity of the swab method was 87%, while the
      sensitivity of the sponge method was 75%. Given the comparable results, use of
      the cheaper and less laborious swab technique is acceptable and may be
      preferable.

PMID- 22461674
TI  - Human cytomegalovirus-specific T-cell immune reconstitution in preemptively
      treated heart transplant recipients identifies subjects at critical risk for
      infection.
AB  - Human cytomegalovirus (CMV) infection represents a major threat for heart
      transplant recipients (HTXs). CMV-specific T cells effectively control virus
      infection, and thus, assessment of antiviral immune recovery may have clinical
      utility in identifying HTXs at risk of infection. In this study, 10 CMV
      seropositive (R(+)) pretransplant patients and 48 preemptively treated R(+) HTXs
      were examined before and after 100 days posttransplant. Preemptive treatment is
      supposed to favor the immune recovery. CMV DNAemia and gamma interferon enzyme
      linked immunosorbent spot (ELISPOT) assay were employed to assess the viremia and
      immune reconstitution. HTXs could be categorized into three groups characterized
      by high (>100), medium (50 to 100), and low (<50) spot levels. Early-identified
      high responders efficiently controlled the infection and also maintained high
      immunity levels after 100 days after transplant. No episodes of grade >=2R
      rejection occurred in the high responders. Midresponders were identified as a
      group with heterogeneous trends of immune reconstitution. Low responders were 41%
      and 21% of HTXs before and after 100 days posttransplant, respectively. Low
      responders were associated with a higher incidence of infection. The effect of
      viremia on immune recovery was investigated: a statistically significant inverse
      correlation between magnitude of viremia and immune recovery emerged; in
      particular, each 10-fold increase in viremia (>4 log(10) DNAemia/ml) was
      associated with a 36% decrease of the ELISPOT assay spot levels. All episodes of
      high viremia (>4 log(10) DNAemia/ml) occurred from 1 to 60 days after transplant.
      Thus, the concomitant evaluation of viremia and CMV immune reconstitution has
      clinical utility in identifying HTXs at risk of infection and may represent a
      helpful guide in making therapeutic choices.

PMID- 22461675
TI  - Comparative evaluation of a prototype chromogenic medium (ChromID CARBA) for
      detecting carbapenemase-producing Enterobacteriaceae in surveillance rectal
      swabs.
AB  - Carbapenemase-producing Enterobacteriaceae (CPE) are an increasing problem
      worldwide, and rectal swab surveillance is recommended as a component of
      infection control programs. The performance of a prototype chromogenic medium
      (chromID CARBA) was evaluated and compared with media tested by four other
      screening methods: (i) overnight selective enrichment in 5 ml tryptic soy broth
      with a 10-MUg ertapenem disk followed by plating onto MacConkey agar (CDC-TS),
      (ii) short selective enrichment in 9 ml brain heart infusion broth with a 10-MUg
      ertapenem disk followed by plating onto chromID ESBL medium (ESBL-BH), (iii)
      direct plating onto chromID ESBL, and (iv) direct plating onto MacConkey agar
      supplemented with meropenem (1 MUg/ml) (MCM). The screening methods were applied
      to detect CPE in 200 rectal swab specimens taken from different hospitalized
      patients. Identification and antimicrobial susceptibility were performed by the
      Vitek 2 system. Carbapenem MICs were checked by Etest. Carbapenemase production
      was confirmed using the modified Hodge test, combined-disk tests, and PCR assays.
      In total, 133 presumptive CPE strains were detected. Phenotypic and genotypic
      assays confirmed 92 strains to be CPE (56 KPC-positive Klebsiella pneumoniae, 29
      VIM-positive K. pneumoniae, and 7 KPC-positive Enterobacter aerogenes strains)
      recovered from 73 patients, while the remaining 41 strains were confirmed to be
      CPE negative (19 ESBL producers and 22 nonfermenters). chromID CARBA, ESBL-BH,
      and chromID ESBL exhibited the highest sensitivity (92.4%), followed by CDC-TS
      and MCM (89.1%) (P = 0.631). The specificity was greater for chromID CARBA
      (96.9%) and ESBL-BH (93.2%) than for CDC-TS (86.4%), MCM (85.2%), and chromID
      ESBL (84.7%) (P = 0.014). In conclusion, chromID CARBA was found to be a rapid
      and accurate culture screening method for active CPE surveillance.

PMID- 22461676
TI  - Is hepatitis C virus core antigen an adequate marker for community screening?
AB  - A new hepatitis C virus (HCV) core antigen (HCV Ag) assay was thought to have a
      good correlation with HCV RNA. The aim was to elucidate the usefulness of this
      HCV Ag assay in community screening. In a township where HCV is endemic, 405
      residents aged 58 years or older responded to a follow-up community screening.
      All subjects were tested for anti-HCV (AxSYM, version 3.0; Abbott Diagnostics)
      and HCV Ag (Architect HCV Ag test; Abbott Diagnostics). For subjects with anti
      HCV signal-to-cutoff ratios (S/CO) > 10 and/or HCV Ag > 3 fmol/liter, HCV RNA
      data (Taqman HCV RNA; Roche Diagnostics) were further checked. A total of 115
      (28.4%) subjects had their serum HCV RNA levels measured, and 93 were HCV RNA
      positive. The other 290 subjects were supposed to be HCV RNA negative. HCV Ag was
      significantly correlated with HCV RNA according to the following equation: (log
      HCV RNA) = 2.08 + 1.03 (log HCV Ag) (R(2) = 0.94; P < 0.001). As determined using
      a combination of the values for anti-HCV (S/CO > 40) and HCV Ag (>3 fmol/liter)
      as a cutoff to predict viremia, the sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value were 96.8%, 100%, 99.3%, 100%,
      and 99%, respectively. In conclusion, for a community study, HCV Ag showed good
      correlation with HCV RNA. In addition, anti-HCV or HCV Ag can predict HCV viremia
      well, while a combination of anti-HCV (>40 S/CO) and HCV Ag (>3 fmol/liter) can
      provide the best result validity.

PMID- 22461677
TI  - Detection of first- and second-line drug resistance in Mycobacterium tuberculosis
      clinical isolates by pyrosequencing.
AB  - Conventional phenotypic drug susceptibility testing (DST) methods for
      Mycobacterium tuberculosis are laborious and very time-consuming. Early detection
      of drug-resistant tuberculosis (TB) is essential for prevention and control of TB
      transmission. We have developed a pyrosequencing method for simultaneous
      detection of mutations associated with resistance to rifampin, isoniazid,
      ethambutol, amikacin, kanamycin, capreomycin, and ofloxacin. Seven pyrosequencing
      assays were optimized for following loci: rpoB, katG, embB, rrs, gyrA, and the
      promoter regions of inhA and eis. The molecular method was evaluated on a panel
      of 290 clinical isolates of M. tuberculosis. In comparison to phenotypic DST, the
      pyrosequencing method demonstrated high specificity (100%) and sensitivity
      (94.6%) for detection of multidrug-resistant M. tuberculosis as well as high
      specificity (99.3%) and sensitivity (86.9%) for detection of extensively drug
      resistant M. tuberculosis. The short turnaround time combined with multilocus
      sequencing of several isolates in parallel makes pyrosequencing an attractive
      method for drug resistance screening in M. tuberculosis.

PMID- 22461678
TI  - Ion torrent personal genome machine sequencing for genomic typing of Neisseria
      meningitidis for rapid determination of multiple layers of typing information.
AB  - Neisseria meningitidis causes invasive meningococcal disease in infants,
      toddlers, and adolescents worldwide. DNA sequence-based typing, including
      multilocus sequence typing, analysis of genetic determinants of antibiotic
      resistance, and sequence typing of vaccine antigens, has become the standard for
      molecular epidemiology of the organism. However, PCR of multiple targets and
      consecutive Sanger sequencing provide logistic constraints to reference
      laboratories. Taking advantage of the recent development of benchtop next
      generation sequencers (NGSs) and of BIGSdb, a database accommodating and
      analyzing genome sequence data, we therefore explored the feasibility and
      accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic
      typing of meningococci. Three strains from a previous meningococcus serogroup B
      community outbreak were selected to compare conventional typing results with data
      generated by semiconductor chip-based sequencing. In addition, sequencing of the
      meningococcal type strain MC58 provided information about the general performance
      of the technology. The PGM technology generated sequence information for all
      target genes addressed. The results were 100% concordant with conventional typing
      results, with no further editing being necessary. In addition, the amount of
      typing information, i.e., nucleotides and target genes analyzed, could be
      substantially increased by the combined use of genome sequencing and BIGSdb
      compared to conventional methods. In the near future, affordable and fast
      benchtop NGS machines like the PGM might enable reference laboratories to switch
      to genomic typing on a routine basis. This will reduce workloads and rapidly
      provide information for laboratory surveillance, outbreak investigation,
      assessment of vaccine preventability, and antibiotic resistance gene monitoring.

PMID- 22461679
TI  - A molecular approach to identification and profiling of first-line-drug-resistant
      mycobacteria from sputum of pulmonary tuberculosis patients.
AB  - Conventional and molecular techniques were applied to detect and characterize
      drug resistance of mycobacteria in the sputum samples of clinically confirmed
      tuberculosis. The sensitivities of mycobacterium detection by ZN staining,
      culture, multiplex PCR, and restriction fragment length polymorphism (RFLP) were
      27.7%, 19.9%, 92.9%, and 95.7%, respectively, but all were 100% specific. The
      conventional and multiple-allele-specific PCR (MAS-PCR) methods enabled
      establishment of the drug resistance in 19.3% and 86.9% cases, respectively. We
      demonstrated that molecular techniques have potential in the accurate diagnosis
      of tuberculosis.

PMID- 22461680
TI  - Correlation of clinical outcomes with beta-glucan levels in patients with
      invasive candidiasis.
AB  - The correlation of beta-glucan (BG) levels with clinical outcomes in invasive
      candidiasis (IC) remains unknown. Patients with proven IC were followed
      prospectively from diagnosis to outcome with twice-weekly serum BG sampling.
      Correlation of BG with clinical outcome was assessed in each patient. BG levels
      tend to decrease in successfully treated patients and increase in treatment
      failures. BG levels may be useful as surrogates for outcome evaluation of IC.

PMID- 22461681
TI  - First case report of bloodstream infection due to a Candida species closely
      related to the novel species Candida pseudorugosa.
AB  - Candida pseudorugosa is a novel species closely related to Candida rugosa for
      which only one case has been reported. We report the first case of a bloodstream
      infection in humans caused by a Candida sp. closely related to C. pseudorugosa.
      We contribute evidence to show this organism as a potential human pathogen that
      may be misidentified by conventional methods, also pointing out its lower
      sensitivity to azoles and other antifungal agents.

PMID- 22461683
TI  - Avascular necrosis of the foot and ankle.

PMID- 22461684
TI  - News media outreach and newspaper coverage of tobacco control.
AB  - INTRODUCTION: Little is known about the impact of media outreach on news media
      coverage of tobacco control. METHODS: Media outreach data were obtained from the
      Centers for Disease Control and Prevention's Office on Smoking and Health
      (CDC/OSH) from 2003 to 2006; one to six types of outreach activities for 50
      scientific publications were performed during 35 discrete time periods. The
      authors analyzed quantitatively and qualitatively 205 newspaper articles
      generated based on the CDC/OSH scientific publications. RESULTS: Media coverage
      of specific CDC/OSH-related tobacco themes was highest for disparities (100%) and
      tobacco statistics (98%). More outreach activities increased the likelihood of
      moderate pickup of the number of themes in newspaper articles (odds ratio = 2.0,
      95% confidence interval = 1.5-2.8), but there appeared to be a ceiling effect.
      Certain types of outreach were more strongly associated with front page and
      headline coverage. CONCLUSIONS: The extent and type of outreach were associated
      with increased newspaper coverage but the relationship is not necessarily
      straightforward. Additional research is needed to better understand relationships
      between scientific findings, outreach, and news media coverage of tobacco.

PMID- 22461685
TI  - Reliability and validity of the hands-up survey in assessing commuting to school
      in New Zealand elementary school children.
AB  - The decrease in physical activity time in and out of school increases the need
      for active commuting. School travel plan programs have been used internationally
      to increase active commuting in elementary school children. However, little
      research has been conducted in the reliability and validity of travel survey
      instruments. The purpose of this study was to evaluate the test-retest
      reliability and validity of the Hands-Up survey to assess active commuting to
      school from a random sample of children within the Auckland region, New Zealand.
      Test-retest reliability and criterion validity of travel modes were determined in
      118 elementary school children in the Auckland region. The survey tool consisted
      of one question on commuting to school. Test-retest reliability and validity were
      evaluated using kappa coefficients. The level of agreement between the children's
      responses (kappa = .96, 95% confidence interval = 0.92-1.00) and between
      children's and parents' (kappa = .91, 95% confidence interval = 0.85-0.98) were
      almost perfect. The Hands-Up survey is a valid and reliable tool to determine
      travel mode to school among elementary school children.

PMID- 22461686
TI  - Sexual health: the role of sexual health services among homeless young women
      living in Toronto, Canada.
AB  - Recent statistics indicate limited condom use, high STI (sexually transmitted
      infection) rates, and a general lack of knowledge about reproductive and sexual
      health among homeless youth. This research focuses on the experiences of homeless
      female and transgendered youth, providing an insider's perspective on shaping
      sexual health interventions. This qualitative research is based on life history
      interviews and participant observation with eight homeless young women who
      reflect the diversity of the homeless population in Toronto, Ontario, Canada.
      Their particularized sexual experiences and health-seeking behaviors illustrate
      the range of issues faced by this community, speaking to the efficacy of current
      health promotion strategies. Too often faced with judgmental health and social
      service providers who they perceive to undermine their agency and empowerment,
      these women highlight the challenges they face when seeking sexual and
      reproductive health services and information. In addition to speaking to the
      struggles and frustrations they face in regard to their sexual health and the
      services with which they choose to interact, the women provide suggestions for
      improved care. From these, the authors include key recommendations for the
      provision of culturally competent, sex-positive, and nonjudgmental health
      services with the hope that health practitioners and promoters can learn from
      these experiences, both positive and negative, when caring for and supporting
      young women living in exceptional circumstances.

PMID- 22461687
TI  - Community-based participatory evaluation: the healthy start approach.
AB  - The use of community-based participatory research has gained momentum as a viable
      approach to academic and community engagement for research over the past 20
      years. This article discusses an approach for extending the process with an
      emphasis on evaluation of a community partnership-driven initiative and thus
      advances the concept of conducting community-based participatory evaluation
      (CBPE) through a model used by the Healthy Start project of the Augusta
      Partnership for Children, Inc., in Augusta, Georgia. Application of the CBPE
      approach advances the importance of bilateral engagements with consumers and
      academic evaluators. The CBPE model shows promise as a reliable and credible
      evaluation approach for community-level assessment of health promotion programs.

PMID- 22461688
TI  - Interview with Dr. Omar Khan, noted global health specialist.
AB  - Dr. Khan has had a distinguished career in global health. He has served as a
      faculty member at the University of Vermont College of Medicine and Johns Hopkins
      University School of Public Health. He is currently a family medicine physician
      at Christiana Care Health System in Newark, Delaware, and is President of the
      Delaware Academy of Family Physicians. Dr. Khan has authored more than 55 peer
      reviewed journal articles and book chapters and has conducted research and lead
      primary care and public health initiatives in numerous countries. Last year, Dr.
      Khan also coedited a book titled Megacities and Global Health sponsored by the
      American Public Health Association with Dr. Gregory Pappas, Deputy Health
      Commissioner for Washington, DC.

PMID- 22461689
TI  - CD4+CD8+ T cells represent a significant portion of the anti-HIV T cell response
      to acute HIV infection.
AB  - Previous studies have revealed that HIV-infected individuals possess circulating
      CD4(+)CD8(+) double-positive (DP) T cells specific for HIV Ags. In the present
      study, we analyzed the proliferation and functional profile of circulating DP T
      cells from 30 acutely HIV-infected individuals and 10 chronically HIV-infected
      viral controllers. The acutely infected group had DP T cells that showed more
      proliferative capability and multifunctionality than did both their CD4(+) and
      CD8(+) T cells. DP T cells were found to exhibit greater proliferation and higher
      multifunctionality compared with CD4 T cells in the viral controller group. The
      DP T cell response represented 16% of the total anti-HIV proliferative response
      and >70% of the anti-HIV multifunctional response in the acutely infected
      subjects. Proliferating DP T cells of the acutely infected subjects responded to
      all HIV Ag pools with equal magnitude. Conversely, the multifunctional response
      was focused on the pool representing Nef, Rev, Tat, VPR, and VPU. Meanwhile, the
      controllers' DP T cells focused on Gag and the Nef, Rev, Tat, VPR, and VPU pool
      for both their proliferative and multifunctional responses. Finally, we show that
      the presence of proliferating DP T cells following all HIV Ag stimulations is
      well correlated with proliferating CD4 T cells whereas multifunctionality appears
      to be largely independent of multifunctionality in other T cell compartments.
      Therefore, DP T cells represent a highly reactive cell population during acute
      HIV infection, which responds independently from the traditional T cell
      compartments.

PMID- 22461690
TI  - Cathepsin G and neutrophil elastase contribute to lung-protective immunity
      against mycobacterial infections in mice.
AB  - The neutrophil serine proteases cathepsin G (CG) and neutrophil elastase (NE) are
      involved in immune-regulatory processes and exert antibacterial activity against
      various pathogens. To date, their role and their therapeutic potential in
      pulmonary host defense against mycobacterial infections are poorly defined. In
      this work, we studied the roles of CG and NE in the pulmonary resistance against
      Mycobacterium bovis bacillus Calmette-Guerin (BCG). CG-deficient mice and even
      more pronounced CG/NE-deficient mice showed significantly impaired pathogen
      elimination to infection with M. bovis BCG in comparison to wild-type mice.
      Moreover, granuloma formation was more pronounced in M. bovis BCG-infected CG/NE
      deficient mice in comparison to CG-deficient and wild-type mice. A close
      examination of professional phagocyte subsets revealed that exclusively
      neutrophils shuttled CG and NE into the bronchoalveolar space of M. bovis BCG
      infected mice. Accordingly, chimeric wild-type mice with a CG/NE-deficient
      hematopoietic system displayed significantly increased lung bacterial loads in
      response to M. bovis BCG infection. Therapeutically applied human CG/NE
      encapsulated in liposomes colocalized with mycobacteria in alveolar macrophages,
      as assessed by laser scanning and electron microscopy. Importantly, therapy with
      CG/NE-loaded liposomes significantly reduced mycobacterial loads in the lungs of
      mice. Together, neutrophil-derived CG and NE critically contribute to
      deceleration of pathogen replication during the early phase of antimycobacterial
      responses. In addition, to our knowledge, we show for the first time that
      liposomal encapsulated CG/NE exhibit therapeutic potential against pulmonary
      mycobacterial infections. These findings may be relevant for novel adjuvant
      approaches in the treatment of tuberculosis in humans.

PMID- 22461691
TI  - Expression of functional P-selectin glycoprotein ligand 1 on hematopoietic
      progenitors is developmentally regulated.
AB  - T cell development requires periodic importation of hematopoietic progenitors
      into the thymus. The receptor-ligand pair P-selectin and P-selectin glycoprotein
      ligand 1 (PSGL-1) are critically involved in this process. In this study, we
      examined the expression of functional PSGL-1 on bone marrow hematopoietic
      progenitors. We demonstrate that functional PSGL-1 is expressed at low levels on
      hematopoietic stem cells, but upregulated on the cell surface of progenitors that
      bear other homing molecules known to be important for thymic settling. We found
      that progenitors able to home to the thymus expressed high levels of PSGL-1
      transcripts compared with hematopoietic stem cells. We further demonstrate that
      hematopoietic progenitors lacking fucosyltransferase 4 and 7 do not express
      functional PSGL-1, and do not home efficiently to the thymus. These studies
      provide insight into the developmentally regulated expression of a critical
      determinant involved in progenitor homing to the thymus.

PMID- 22461692
TI  - TGF-beta converts apoptotic stimuli into the signal for Th9 differentiation.
AB  - Naturally arising CD4(+)CD25(+)FoxP3(+) regulatory T cells (nTregs) have an
      essential role in maintenance of immune homeostasis and peripheral tolerance.
      Previously, we reported that conventional CD4(+) and CD8(+) T cells undergo p53
      induced CD28-dependent apoptosis (PICA) when stimulated with a combination of
      immobilized anti-CD3 and anti-CD28 Abs, whereas nTregs expand robustly under the
      same conditions, suggesting that there is a differential survival mechanism
      against PICA between conventional T cells and nTregs. In this study, we
      demonstrate that TGF-beta signaling is required for nTregs to survive PICA.
      Conversely, when an active form of exogenous TGF-beta is present, conventional T
      cells become resistant to PICA and undergo robust expansion instead of apoptosis,
      with reduction of the proapoptotic protein Bim and FoxO3a. A substantial fraction
      of PICA-resistant T cells expressed IL-9 (T(H)9 cells). Moreover, the presence of
      IL-6 along with TGF-beta led to the generation of T(H)17 cells from conventional
      T cells. Together, the data demonstrate a novel role for TGF-beta in the
      homeostasis of regulatory T cells and effector T cell differentiation and
      expansion.

PMID- 22461693
TI  - Different adaptations of IgG effector function in human and nonhuman primates and
      implications for therapeutic antibody treatment.
AB  - Safety of human therapeutic Abs is generally assessed in nonhuman primates.
      Whereas IgG1 shows identical FcgammaR interaction and effector function profile
      in both species, fundamental differences in the IgG2 and IgG4 Ab subclasses were
      found between the two species. Granulocytes, the main effector cells against IgG2
      and IgG4-opsonized bacteria and parasites, do not express FcgammaRIIIb, but show
      higher levels of FcgammaRII in cynomolgus monkey. In humans, IgG2 and IgG4
      adapted a silent Fc region with weak binding to FcgammaR and effector functions,
      whereas, in contrast, cynomolgus monkey IgG2 and IgG4 display strong effector
      function as well as differences in IgG4 Fab arm exchange. To balance this shift
      toward activation, the cynomolgus inhibitory FcgammaRIIb shows strongly increased
      affinity for IgG2. In view of these findings, in vitro and in vivo results for
      human IgG2 and IgG4 obtained in the cynomolgus monkey have to be cautiously
      interpreted, whereas effector function-related effects of human IgG1 Abs are
      expected to be predictable for humans.

PMID- 22461694
TI  - Rhinovirus-induced MMP-9 expression is dependent on Fra-1, which is modulated by
      formoterol and dexamethasone.
AB  - Matrix metalloproteinase-9 is implicated in airway inflammation and airway
      remodeling in asthma. We have previously confirmed that human rhinovirus-16 (HRV
      16) infection increases MMP-9 expression both in vivo and in vitro. However, the
      role of the AP-1 sites within the MMP-9 promoter and the effect of commonly used
      asthma pharmacotherapies in modulating human rhinovirus (HRV)-induced MMP-9
      production have not yet been elucidated. Experiments were performed in vitro in
      the human bronchial epithelial (HBE) cell line BEAS-2B and in primary HBE cells
      obtained from non-transplanted lungs. Using site-directed mutagenesis approaches,
      AP-1 sites were found to be necessary for HRV-induced MMP-9 promoter drive. EMSAs
      and supershift assays identified complexes consisting of Fos-related Ag-1 (Fra-1)
      in addition to other AP-1 subunits. Small interfering RNA approaches indicated
      that Fra-1 was induced upon HRV-16 infection in BEAS-2B cells and was necessary
      for MMP-9 expression in both BEAS-2B and primary HBE cells. Inhibition of MEK1/2
      activity using PD98059 and U0126 reduced Fra-1 expression, DNA binding, MMP-9
      promoter drive, and MMP-9 protein production. The long-acting beta(2)-agonist
      formoterol and the glucocorticoid dexamethasone significantly reduced HRV-induced
      ERK phosphorylation, Fra-1, and MMP-9 expression in BEAS-2B cells. These data
      indicate that HRV-induced activation of the MEK/ERK MAPK pathway and Fra-1
      expression are necessary for the upregulation of MMP-9 and can be modulated by
      two distinct but commonly used asthma pharmacotherapies. Together, these results
      offer insights into the mechanisms by which long-acting beta(2)-agonists and
      glucocorticoids might reduce HRV-related asthma exacerbations.

PMID- 22461695
TI  - Decitabine and vorinostat cooperate to sensitize colon carcinoma cells to Fas
      ligand-induced apoptosis in vitro and tumor suppression in vivo.
AB  - The death receptor Fas and its physiological ligand (FasL) regulate apoptosis of
      cancerous cells, thereby functioning as a critical component of the host cancer
      immunosurveillance system. To evade Fas-mediated apoptosis, cancer cells often
      downregulate Fas to acquire an apoptosis-resistant phenotype, which is a hallmark
      of metastatic human colorectal cancer. Therefore, targeting Fas resistance is of
      critical importance in Fas-based cancer therapy and immunotherapy. In this study,
      we demonstrated that epigenetic inhibitors decitabine and vorinostat cooperate to
      upregulate Fas expression in metastatic human colon carcinoma cells. Decitabine
      also upregulates BNIP3 and Bik expression, whereas vorinostat decreased Bcl-x(L)
      expression. Altered expression of Fas, BNIP3, Bik, and Bcl-x(L) resulted in
      effective sensitization of the metastatic human colon carcinoma cells to FasL
      induced apoptosis. Using an experimental metastasis mouse model, we further
      demonstrated that decitabine and vorinostat cooperate to suppress colon carcinoma
      metastasis. Analysis of tumor-bearing lung tissues revealed that a large portion
      of tumor-infiltrating CD8(+) T cells are FasL(+), and decitabine and vorinostat
      mediated tumor-suppression efficacy was significantly decreased in Fas(gld) mice
      compared with wild-type mice, suggesting a critical role for FasL in decitabine
      and vorinostat-mediated tumor suppression in vivo. Consistent with their function
      in apoptosis sensitization, decitabine and vorinostat significantly increased the
      efficacy of CTL adoptive transfer immunotherapy in an experimental metastasis
      mouse model. Thus, our data suggest that combined modalities of chemotherapy to
      sensitize the tumor cell to Fas-mediated apoptosis and CTL immunotherapy is an
      effective approach for the suppression of colon cancer metastasis.

PMID- 22461697
TI  - CD47(high) expression on CD4 effectors identifies functional long-lived memory T
      cell progenitors.
AB  - T cell memory is the hallmark of adaptive immunity. Central questions are to
      determine which cells among proliferating effector T cells will live beyond the
      crash of the immune response (IR) and develop into functional memory T cells.
      CD47, considered as a marker of self, is implicated in cell death, cell
      elimination, and in the inflammatory response. We report in this article that
      CD47 expression was transiently regulated on Ag-specific CD4 T cells, that is,
      from CD47(high) to CD47(low) to CD47(high), during the course of the in vivo IR.
      Specifically, CD47(high) status marked central memory CD4 T cell precursors at an
      early time point of the IR. By contrast, cytokine production was a functional
      attribute restricted to CD47(high), but not CD47(low), polyclonal effector CD4 T
      cells during recall responses in an experimental model of chronic airway
      inflammatory disease. Passive transfer of CD47(high), but not CD47(low), CD4 T
      cells in nonlymphopenic naive mice generated long-lived memory T cells capable of
      anamnestic responses. We conclude that CD47(high) status on CD4 T cells
      identifies functional long-lived memory T cell progenitors.

PMID- 22461696
TI  - Heme oxygenase-1 promotes the persistence of Leishmania chagasi infection.
AB  - Visceral leishmaniasis (VL) remains a major public health problem worldwide. This
      disease is highly associated with chronic inflammation and a lack of the cellular
      immune responses against Leishmania. It is important to identify major factors
      driving the successful establishment of the Leishmania infection to develop
      better tools for the disease control. Heme oxygenase-1 (HO-1) is a key enzyme
      triggered by cellular stress, and its role in VL has not been investigated. In
      this study, we evaluated the role of HO-1 in the infection by Leishmania infantum
      chagasi, the causative agent of VL cases in Brazil. We found that L. chagasi
      infection or lipophosphoglycan isolated from promastigotes triggered HO-1
      production by murine macrophages. Interestingly, cobalt protoporphyrin IX, an HO
      1 inductor, increased the parasite burden in both mouse and human-derived
      macrophages. Upon L. chagasi infection, macrophages from Hmox1 knockout mice
      presented significantly lower parasite loads when compared with those from wild
      type mice. Furthermore, upregulation of HO-1 by cobalt protoporphyrin IX
      diminished the production of TNF-alpha and reactive oxygen species by infected
      murine macrophages and increased Cu/Zn superoxide dismutase expression in human
      monocytes. Finally, patients with VL presented higher systemic concentrations of
      HO-1 than healthy individuals, and this increase of HO-1 was reduced after
      antileishmanial treatment, suggesting that HO-1 is associated with disease
      susceptibility. Our data argue that HO-1 has a critical role in the L. chagasi
      infection and is strongly associated with the inflammatory imbalance during VL.
      Manipulation of HO-1 pathways during VL could serve as an adjunctive therapeutic
      approach.

PMID- 22461699
TI  - Components of Streptococcus pneumoniae suppress allergic airways disease and NKT
      cells by inducing regulatory T cells.
AB  - Asthma is an allergic airways disease (AAD) caused by dysregulated immune
      responses and characterized by eosinophilic inflammation, mucus hypersecretion,
      and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to
      AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant
      immune responses and maintain homeostasis. Recent evidence suggests that
      Streptococcus pneumoniae induces Tregs that have potential to be harnessed
      therapeutically for asthma. In this study, mouse models of AAD were used to
      identify the S. pneumoniae components that have suppressive properties, and the
      mechanisms underlying suppression were investigated. We tested the suppressive
      capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply)
      and CpG. When coadministered, T3P + Ply suppressed the development of:
      eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR.
      Importantly, T3P + Ply also attenuated features of AAD when administered during
      established disease. We show that NKT cells contributed to the development of AAD
      and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer
      of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply
      induced Tregs were essential for the suppression of NKT cells and AAD, which was
      demonstrated by Treg depletion. Collectively, our results show that the S.
      pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that
      blocked the activity of NKT cells. These data suggest that S. pneumoniae
      components may have potential as a therapeutic strategy for the suppression of
      allergic asthma through the induction of Tregs and suppression of NKT cells.

PMID- 22461698
TI  - Intracellular heat shock protein-70 negatively regulates TLR4 signaling in the
      newborn intestinal epithelium.
AB  - Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal-related
      mortality in premature infants, and it develops under conditions of exaggerated
      TLR4 signaling in the newborn intestinal epithelium. Because NEC does not develop
      spontaneously, despite the presence of seemingly tonic stimulation of intestinal
      TLR4, we hypothesized that mechanisms must exist to constrain TLR4 signaling that
      become diminished during NEC pathogenesis and focused on the intracellular stress
      response protein and chaperone heat shock protein-70 (Hsp70). We demonstrate that
      the induction of intracellular Hsp70 in enterocytes dramatically reduced TLR4
      signaling, as assessed by LPS-induced NF-kappaB translocation, cytokine
      expression, and apoptosis. These findings were confirmed in vivo, using mice that
      either globally lacked Hsp70 or overexpressed Hsp70 within the intestinal
      epithelium. TLR4 activation itself significantly increased Hsp70 expression in
      enterocytes, which provided a mechanism of autoinhibition of TLR4 signaling in
      enterocytes. In seeking to define the mechanisms involved, intracellular Hsp70
      mediated inhibition of TLR4 signaling required both its substrate-binding EEVD
      domain and association with the cochaperone CHIP, resulting in ubiquitination and
      proteasomal degradation of TLR4. The expression of Hsp70 in the intestinal
      epithelium was significantly decreased in murine and human NEC compared with
      healthy controls, suggesting that loss of Hsp70 protection from TLR4 could lead
      to NEC. In support of this, intestinal Hsp70 overexpression in mice and
      pharmacologic upregulation of Hsp70 reversed TLR4-induced cytokines and
      enterocyte apoptosis, as well as prevented and treated experimental NEC. Thus, a
      novel TLR4 regulatory pathway exists within the newborn gut involving Hsp70 that
      may be pharmacologically activated to limit NEC severity.

PMID- 22461700
TI  - Chronic helminth infection reduces basophil responsiveness in an IL-10-dependent
      manner.
AB  - Basophils play a key role in the development and effector phases of type 2 immune
      responses in both allergic diseases and helminth infections. This study shows
      that basophils become less responsive to IgE-mediated stimulation when mice are
      chronically infected with Litomosoides sigmodontis, a filarial nematode, and
      Schistosoma mansoni, a blood fluke. Although excretory/secretory products from
      microfilariae of L. sigmodontis suppressed basophils in vitro, transfer of
      microfilariae into mice did not result in basophil suppression. Rather, reduced
      basophil responsiveness, which required the presence of live helminths, was found
      to be dependent on host IL-10 and was accompanied by decreases in key IgE
      signaling molecules known to be downregulated by IL-10. Given the importance of
      basophils in the development of type 2 immune responses, these findings help
      explain the mechanism by which helminths protect against allergy and may have
      broad implications for understanding how helminth infections alter other disease
      states in people.

PMID- 22461701
TI  - HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple
      sclerosis.
AB  - It was hypothesized that the EBV-specific CD8(+) T cell response may be
      dysregulated in multiple sclerosis (MS) patients, possibly leading to a
      suboptimal control of this virus. To examine the CD8(+) T cell response in
      greater detail, we analyzed the HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and
      CMV-specific CD8(+) T cell responses in a high number of MS patients and control
      subjects using tetramers. Content in cytolytic granules, as well as cytotoxic
      activity, of EBV- and CMV-specific CD8(+) T cells was assessed. We found that MS
      patients had a lower or a higher prevalence of HLA-A2 and HLA-B7, respectively.
      Using HLA class I tetramers in HLA-B7(+) MS patients, there was a higher
      prevalence of MS patients with HLA-B*0702/EBV(RPP)-specific CD8(+) T cells ex
      vivo. However, the magnitude of the HLA-B*0702/EBV(RPP)-specific and HLA
      B*0702/CMV(TPR)-specific CD8(+) T cell response (i.e., the percentage of
      tetramer(+) CD8(+) T cells in a study subject harboring CD8(+) T cells specific
      for the given epitope) was lower in MS patients. No differences were found using
      other tetramers. After stimulation with the HLA-B*0702/EBV(RPP) peptide, the
      production of IL-2, perforin, and granzyme B and the cytotoxicity of HLA
      B*0702/EBV(RPP)-specific CD8(+) T cells were decreased. Altogether, our findings
      suggest that the HLA-B*0702-restricted viral (in particular the EBV one)-specific
      CD8(+) T cell response is dysregulated in MS patients. This observation is
      particularly interesting knowing that the HLA-B7 allele is more frequently
      expressed in MS patients and considering that EBV is associated with MS.

PMID- 22461703
TI  - Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes
      to diminished CD4+CD25+ regulatory T cell function.
AB  - Numerous reports have demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs)
      from individuals with a range of human autoimmune diseases, including type 1
      diabetes, are deficient in their ability to control autologous proinflammatory
      responses when compared with nondiseased, control individuals. Treg dysfunction
      could be a primary, causal event or may result from perturbations in the immune
      system during disease development. Polymorphisms in genes associated with Treg
      function, such as IL2RA, confer a higher risk of autoimmune disease. Although
      this suggests a primary role for defective Tregs in autoimmunity, a link between
      IL2RA gene polymorphisms and Treg function has not been examined. We addressed
      this by examining the impact of an IL2RA haplotype associated with type 1
      diabetes on Treg fitness and suppressive function. Studies were conducted using
      healthy human subjects to avoid any confounding effects of disease. We
      demonstrated that the presence of an autoimmune disease-associated IL2RA
      haplotype correlates with diminished IL-2 responsiveness in Ag-experienced CD4(+)
      T cells, as measured by phosphorylation of STAT5a, and is associated with lower
      levels of FOXP3 expression by Tregs and a reduction in their ability to suppress
      proliferation of autologous effector T cells. These data offer a rationale that
      contributes to the molecular and cellular mechanisms through which polymorphisms
      in the IL-2RA gene affect immune regulation, and consequently upon susceptibility
      to autoimmune and inflammatory diseases.

PMID- 22461704
TI  - Hepatitis C virus seroprevalence in the Netherlands.
AB  - A population-based anti-hepatitis C virus (HCV) prevalence is important for
      surveillance purposes and it provides an insight into the burden of disease. In
      The Netherlands, a recent HCV seroprevalence estimate is not available. This
      national population-based cross-sectional serosurvey (PIENTER-2) resulted in a
      weighted national HCV seroprevalence of 0.30% (95% confidence interval 0.05
      0.55%). About 70% of the HCV positive individuals found were born in an HCV
      endemic country.

PMID- 22461702
TI  - Intracellular insulin-like growth factor-1 induces Bcl-2 expression in airway
      epithelial cells.
AB  - Bcl-2, a prosurvival protein, regulates programmed cell death during development
      and repair processes, and it can be oncogenic when cell proliferation is
      deregulated. The present study investigated what factors modulate Bcl-2
      expression in airway epithelial cells and identified the pathways involved.
      Microarray analysis of mRNA from airway epithelial cells captured by laser
      microdissection showed that increased expression of IL-1beta and insulin-like
      growth factor-1 (IGF-1) coincided with induced Bcl-2 expression compared with
      controls. Treatment of cultured airway epithelial cells with IL-1beta and IGF-1
      induced Bcl-2 expression by increasing Bcl-2 mRNA stability with no discernible
      changes in promoter activity. Silencing the IGF-1 expression using short hairpin
      RNA showed that intracellular IGF-1 (IC-IGF-1) was increasing Bcl-2 expression.
      Blocking epidermal growth factor receptor or IGF-1R activation also suppressed IC
      IGF-1 and abolished the Bcl-2 induction. Induced expression and colocalization of
      IC-IGF-1 and Bcl-2 were observed in airway epithelial cells of mice exposed to
      LPS or cigarette smoke and of patients with cystic fibrosis and chronic
      bronchitis but not in the respective controls. These studies demonstrate that IC
      IGF-1 induces Bcl-2 expression in epithelial cells via IGF-1R and epidermal
      growth factor receptor pathways, and targeting IC-IGF-1 could be beneficial to
      treat chronic airway diseases.

PMID- 22461706
TI  - Shortages of medicines: a complex global challenge.

PMID- 22461708
TI  - Connecting and caring: innovations for healthy ageing.

PMID- 22461709
TI  - Awareness is the first step in battle against breast cancer.

PMID- 22461710
TI  - Don't let torture victims fall through the cracks. Interview by Fiona Fleck.

PMID- 22461711
TI  - Elimination of paediatric HIV in KwaZulu-Natal, South Africa: large-scale
      assessment of interventions for the prevention of mother-to-child transmission.
AB  - OBJECTIVE: To report the rates of mother-to-child transmission (MTCT) of the
      human immunodeficiency virus (HIV), and the coverage of interventions designed to
      prevent such transmission, in KwaZulu-Natal. METHODS: Mothers with infants aged
      <= 16 weeks and fathers or legal guardians with infants aged 4-8 weeks who,
      between May 2008 and April 2009, attended immunization clinics in six districts
      of KwaZulu-Natal were included. The mothers' uptake of interventions for the
      prevention of MTCT was explored. Blood samples from infants aged 4-8 weeks were
      tested for anti-HIV antibodies and, if antibody-positive, for HIV
      desoxyribonucleic acid (DNA). FINDINGS: Of the 19,494 mothers investigated, 89.9%
      reported having had an HIV test in their recent pregnancy. Of the 19,138 mothers
      who reported ever having had an HIV test, 34.4% reported that they had been found
      HIV-positive and, of these, 13.7% had started lifelong antiretroviral treatment
      and 67.2% had received zidovudine and nevirapine. Overall, 40.4% of the 7981
      infants tested were found positive for anti-HIV antibodies, indicating HIV
      exposure. Just 7.1% of the infants checked for HIV DNA (equating to 2.8% of the
      infants tested for anti-HIV antibodies) were found positive. CONCLUSION: The low
      levels of MTCT observed among the infants indicate the rapid, successful
      implementation of interventions for the prevention of such transmission. Sampling
      at immunization clinics appears to offer a robust method of estimating the impact
      of interventions designed to reduce such transmission. Large-scale elimination of
      paediatric HIV infections appears feasible, although this goal has not yet been
      fully achieved in KwaZulu-Natal.

PMID- 22461712
TI  - Improving public health information: a data quality intervention in KwaZulu
      Natal, South Africa.
AB  - OBJECTIVE: To evaluate the effect of an intervention to improve the quality of
      data used to monitor the prevention of mother-to-child transmission (PMTCT) of
      the human immunodeficiency virus in South Africa. METHODS: The study involved 58
      antenatal clinics and 20 delivery wards (37 urban, 21 rural and 20 semi-urban) in
      KwaZulu-Natal province that provided PMTCT services and reported data to the
      District Health Information System. The data improvement intervention, which was
      implemented between May 2008 and March 2009, involved training on data collection
      and feedback for health information personnel and programme managers, monthly
      data reviews and data audits at health-care facilities. Data on six data elements
      used to monitor PMTCT services and recorded in the information system were
      compared with source data from health facility registers before, during and after
      the intervention. Data completeness (i.e. their presence in the system) and
      accuracy (i.e. being within 10% of their true value) were evaluated. FINDINGS:
      The level of data completeness increased from 26% before to 64% after the
      intervention. Similarly, the proportion of data in the information system
      considered accurate increased from 37% to 65% (P < 0.0001). Moreover, the
      correlation between data in the information system and those from facility
      registers rose from 0.54 to 0.92. CONCLUSION: A simple, practical data
      improvement intervention significantly increased the completeness and accuracy of
      the data used to monitor PMTCT services in South Africa.

PMID- 22461713
TI  - Community case management of childhood illnesses: policy and implementation in
      Countdown to 2015 countries.
AB  - OBJECTIVE: To explore the policies for, and implementation of, the community case
      management (CCM) of childhood illnesses in the 68 countries that were prioritized
      by the "Countdown to 2015" initiative in 2008. METHODS: In 2009-2010, community
      approaches concerning CCM policy and implementation, the roles of community
      health workers (CHWs) and the availability of medicines for the treatment of
      malaria, diarrhoea, pneumonia and neonatal infections were investigated by
      sending questionnaires to implementers and policy-makers and through telephone
      discussions with appropriate researchers and experts. FINDINGS: Of the 59
      countries that responded, 81%, 75%, 54% and 14% had a policy for the CCM of
      diarrhoea, malaria, pneumonia and neonatal infections, respectively. Only three
      (6%) of the 53 malaria-endemic countries providing responses had policies for all
      four of these conditions, although 17 (32%) had CCM policies for malaria,
      diarrhoea and pneumonia. Some CCM of childhood illnesses was being implemented-
      more commonly for diarrhoea and malaria than for pneumonia or neonatal infections
      -in 88% of the countries providing responses. According to the responses
      received, CHWs administered the recommended treatments for diarrhoea, malaria or
      pneumonia in 34% (17/50), 100% (41/41) and 100% (34/34) of the countries
      implementing CCM of these conditions, respectively. Common programme concerns
      were drug supplies, quality of care and CHW incentives, training and supervision.
      CONCLUSION: Despite progress, further efforts are needed towards policy reform
      and the expansion of CCM programmes. Ensuring the availability of recommended
      medicines and operational research, to assure quality, remain priorities.

PMID- 22461714
TI  - External quality assessment of national public health laboratories in Africa,
      2002-2009.
AB  - OBJECTIVE: To describe findings from an external quality assessment programme
      involving laboratories in Africa that routinely investigate epidemic-prone
      diseases. METHODS: Beginning in 2002, the Regional Office for Africa of the World
      Health Organization (WHO) invited national public health laboratories and related
      facilities in Africa to participate in the programme. Three surveys comprising
      specimens and questionnaires associated with bacterial enteric diseases,
      bacterial meningitis, plague, tuberculosis and malaria were sent annually to test
      participants' diagnostic proficiency. Identical surveys were sent to referee
      laboratories for quality control. Materials were prepared, packaged and shipped
      in accordance with standard protocols. Findings and reports were due within 30
      days. Key methodological decisions and test results were categorized as
      acceptable or unacceptable on the basis of consensus feedback from referees,
      using established grading schemes. FINDINGS: Between 2002 and 2009, participation
      increased from 30 to 48 Member States of the WHO and from 39 to 78 laboratories.
      Each survey was returned by 64-93% of participants. Mean turnaround time was 25.9
      days. For bacterial enteric diseases and meningitis components, bacterial
      identification was acceptable in 65% and 69% of challenges, respectively, but
      serotyping and antibiotic susceptibility testing and reporting were frequently
      unacceptable. Microscopy was acceptable for 73% of plague challenges.
      Tuberculosis microscopy was satisfactorily performed, with 87% of responses
      receiving acceptable scores. In the malaria component, 82% of responses received
      acceptable scores for species identification but only 51% of parasite
      quantitation scores were acceptable. CONCLUSION: The external quality assessment
      programme consistently identified certain functional deficiencies requiring
      strengthening that were present in African public health microbiology
      laboratories.

PMID- 22461715
TI  - Birth attendants as perinatal verbal autopsy respondents in low- and middle
      income countries: a viable alternative?
AB  - OBJECTIVE: To assess the feasibility of using birth attendants instead of
      bereaved mothers as perinatal verbal autopsy respondents. METHODS: Verbal autopsy
      interviews for early neonatal deaths and stillbirths were conducted separately
      among mothers (reference standard) and birth attendants in 38 communities in four
      developing countries. Concordance between maternal and attendant responses was
      calculated for all questions, for categories of questions and for individual
      questions. The sensitivity and specificity of individual questions with the birth
      attendant as respondent were assessed. FINDINGS: For early neonatal deaths,
      concordance across all questions was 94%. Concordance was at least 95% for more
      than half the questions on maternal medical history, birth attendance and neonate
      characteristics. Concordance on any given question was never less than 80%.
      Sensitivity and specificity varied across individual questions, more than 80% of
      which had a sensitivity of at least 80% and a specificity of at least 90%.  For
      stillbirths, concordance across all questions was 93%. Concordance was 95% or
      greater more than half the time for questions on birth attendance, site of
      delivery and stillborn characteristics. Sensitivity and specificity varied across
      individual questions. Over 60% of the questions had a sensitivity of at least 80%
      and over 80% of them had a specificity of at least 90%. Overall, the causes of
      death established through verbal autopsy were similar, regardless of respondent.
      CONCLUSION: Birth attendants can substitute for bereaved mothers as verbal
      autopsy respondents. The questions in existing harmonized verbal autopsy
      questionnaires need further refinement, as their sensitivity and specificity
      differ widely.

PMID- 22461717
TI  - Practical measurement of affordability: an application to medicines.
AB  - OBJECTIVE: To develop two practical methods for measuring the affordability of
      medicines in developing countries. METHODS: The proposed methods--catastrophic
      and impoverishment methods--rely on easily accessible aggregated expenditure data
      and take into account a country's income distribution and absolute level of
      income. The catastrophic method quantifies the proportion of the population whose
      resources would be catastrophically reduced by spending on a given medicine; the
      impoverishment method estimates the proportion of the population that would be
      pushed below the poverty line by procuring a given medicine. These methods are
      illustrated by calculating the affordability of glibenclamide, an antidiabetic
      drug, in India and Indonesia. The results were validated by comparing them with
      the results obtained by using household micro data for India and Indonesia.
      FINDINGS: When accurate aggregate data are available, the proposed methods offer
      a practical way to obtain informative and accurate estimates of affordability.
      Their results are very similar to those obtained with household micro data
      analysis and are easily compared across countries. CONCLUSION: The catastrophic
      and impoverishment methods, based on macro data, can provide a suitable estimate
      of medicine affordability when the household level micro data needed to carry out
      more sophisticated studies are not available. Their usefulness depends on the
      availability of accurate aggregated data.

PMID- 22461716
TI  - The global burden of cholera.
AB  - OBJECTIVE: To estimate the global burden of cholera using population-based
      incidence data and reports. METHODS: Countries with a recent history of cholera
      were classified as endemic or non-endemic, depending on whether they had reported
      cholera cases in at least three of the five most recent years. The percentages of
      the population in each country that lacked access to improved sanitation were
      used to compute the populations at risk for cholera, and incidence rates from
      published studies were applied to groups of countries to estimate the annual
      number of cholera cases in endemic countries. The estimates of cholera cases in
      non-endemic countries were based on the average numbers of cases reported from
      2000 to 2008. Literature-based estimates of cholera case-fatality rates (CFRs)
      were used to compute the variance-weighted average cholera CFRs for estimating
      the number of cholera deaths. FINDINGS: About 1.4 billion people are at risk for
      cholera in endemic countries. An estimated 2.8 million cholera cases occur
      annually in such countries (uncertainty range: 1.4-4.3) and an estimated 87,000
      cholera cases occur in non-endemic countries. The incidence is estimated to be
      greatest in children less than 5 years of age. Every year about 91,000 people
      (uncertainty range: 28,000 to 142,000) die of cholera in endemic countries and
      2500 people die of the disease in non-endemic countries. CONCLUSION: The global
      burden of cholera, as determined through a systematic review with clearly stated
      assumptions, is high. The findings of this study provide a contemporary basis for
      planning public health interventions to control cholera.

PMID- 22461718
TI  - Accounting for water quality in monitoring access to safe drinking-water as part
      of the Millennium Development Goals: lessons from five countries.
AB  - OBJECTIVE: To determine how data on water source quality affect assessments of
      progress towards the 2015 Millennium Development Goal (MDG) target on access to
      safe drinking-water. METHODS: Data from five countries on whether drinking-water
      sources complied with World Health Organization water quality guidelines on
      contamination with thermotolerant coliform bacteria, arsenic, fluoride and
      nitrates in 2004 and 2005 were obtained from the Rapid Assessment of Drinking
      Water Quality project. These data were used to adjust estimates of the proportion
      of the population with access to safe drinking-water at the MDG baseline in 1990
      and in 2008 made by the Joint Monitoring Programme for Water Supply and
      Sanitation, which classified all improved sources as safe. FINDINGS: Taking
      account of data on water source quality resulted in substantially lower estimates
      of the percentage of the population with access to safe drinking-water in 2008 in
      four of the five study countries: the absolute reduction was 11% in Ethiopia, 16%
      in Nicaragua, 15% in Nigeria and 7% in Tajikistan. There was only a slight
      reduction in Jordan. Microbial contamination was more common than chemical
      contamination. CONCLUSION: The criterion used by the MDG indicator to determine
      whether a water source is safe can lead to substantial overestimates of the
      population with access to safe drinking-water and, consequently, also
      overestimates the progress made towards the 2015 MDG target. Monitoring drinking
      water supplies by recording both access to water sources and their safety would
      be a substantial improvement.

PMID- 22461719
TI  - Putting the priorities first: medicines for maternal and child health.

PMID- 22461720
TI  - Surgical epidemiology: a call for action.

PMID- 22461721
TI  - Ethical tensions in dealing with noncommunicable diseases globally.

PMID- 22461722
TI  - Reinforcing cholera intervention through prediction-aided prevention.

PMID- 22461723
TI  - Needed: Longitudinal Research That Can Inform Dynamic Models for the Treatment of
      Addiction as a Disease.

PMID- 22461725
TI  - A catalogue of Lithuanian beetles (Insecta, Coleoptera).
AB  - This paper presents the first complete and updated list of all 3597 species of
      beetles (Insecta: Coleoptera) belonging to 92 familiesfound and published in
      Lithuania until 2011, with comments also provided on the main systematic and
      nomenclatural changes since the last monographic treatment in two volumes
      (Pileckis and Monsevicius 1995, 1997). The introductory section provides a
      general overview of the main features of the territory of Lithuania, the origins
      and formation of the beetle fauna and their conservation, the faunistic
      investigations in Lithuania to date revealing the most important stages of the
      faunistic research process with reference to the most prominent scientists, an
      overview of their work, and their contribution to Lithuanian coleopteran faunal
      research.Species recorded in Lithuania by some authors without reliable evidence
      and requiring further confirmation with new data are presented in a separate
      list, consisting of 183 species. For the first time, analysis of errors in works
      of Lithuanian authors concerning data on coleopteran fauna has been conducted and
      these errors have been corrected. All available published and Internet sources on
      beetles found in Lithuania have been considered in the current study. Over 630
      literature sources on species composition of beetles, their distribution in
      Lithuania and neighbouring countries, and taxonomic revisions and changes are
      reviewed and cited. An alphabetical list of these literature sources is
      presented. After revision of public beetle collections in Lithuania, the authors
      propose to remove 43 species from the beetle species list of the country on the
      grounds, that they have been wrongly identified or published by mistake. For
      reasons of clarity, 19 previously noted but later excluded species are included
      in the current checklist with comments. Based on faunal data from neighbouring
      countries, species expected to occur in Lithuania are matnioned. In total 1390
      species are attributed to this category and data on their distribution in
      neighbouring countries is presented. Completion of this study provides evidence
      that the Lithuanian coleopteran fauna has yet to be completely investigated and
      it is estimated that approximately 28 % of beetle species remain undiscovered in
      Lithuania. More than 85% of beetle species expected for Lithuania have been found
      in the following families: Cerylonidae, Geotrupidae, Haliplidae, Kateridae,
      Lycidae, Lucanidae, Mycetophagidae, Scarabaeidae and Silphidae. In families with
      few species such as Alexiidae, Boridae, Byturidae, Dascilidae, Drilidae,
      Eucinetidae, Lampyridae, Lymexilidae, Megalopodidae, Nemonychidae, Nosodendridae,
      Noteridae, Orsodacnidae, Pyrochroidae, Pythidae, Psephenidae, Rhysodidae,
      Sphaeritidae, Sphaeriusidae, Sphindidae, Stenotrahelidae and Trogidae, all
      possible species have already been discovered. However in some beetle families
      such as Aderidae, Bothrideridae, Eucnemidae, Laemoploeidae, Mordellidae,
      Ptiliidae, Scraptidae and Throscidae less than 50% of all possible species are
      known. At present the beetle species recorded in Lithuania belong to 92 families,
      with species from 9 other families such as Agyrtidae, Biphylidae, Deradontidae,
      Mycteridae, Ochodaeidae, Phleophilidae, Phloeostichidae, Prostomidae,
      Trachypachidae are expected to be found.A bibliography and a index of subfamily
      and genus levels are provided. The information published in the monograph will
      serve to further faunistic and distribution research of beetles and will help to
      avoid confusion in the identificatation of coleopteran fauna of Lithuania.

PMID- 22461724
TI  - Effect of PGC-1alpha on proliferation, migration, and transdifferentiation of rat
      vascular smooth muscle cells induced by high glucose.
AB  - We assessed the role of PGC-1alpha (PPARgamma coactivator-1 alpha) in glucose
      induced proliferation, migration, and inflammatory gene expression of vascular
      smooth muscle cells (VSMCs). We carried out phagocytosis studies to assess the
      role of PGC-1alpha in transdifferentiation of VSMCs by flow cytometry. We found
      that high glucose stimulated proliferation, migration and inflammatory gene
      expression of VSMCs, but overexpression of PGC-1alpha attenuated the effects of
      glucose. In addition, overexpression of PGC-1alpha decreased mRNA and protein
      level of VSMCs-related genes, and induced macrophage-related gene expression, as
      well as phagocytosis of VSMCs. Therefore, PGC-1alpha inhibited glucose-induced
      proliferation, migration and inflammatory gene expression of VSMCs, which are key
      features in the pathology of atherosclerosis. More importantly, PGC-1alpha
      transdifferentiated VSMCs to a macrophage-like state. Such transdifferentiation
      possibly increased the portion of VSMCs-derived foam cells in the plaque and
      favored plaque stability.

PMID- 22461726
TI  - Alatococcus, a new genus of Sapindaceae from Espirito Santo, Brazil.
AB  - The new genus Alatococcus (Sapindaceae) is described from Espirito Santo, Brazil.
      Alatococcus seems to be closely related to Scyphonychium of northeastern Brazil,
      as they both share similar vegetative morphology, flowers with zygomorphic calyx,
      fruits with indehiscent mericarps, and isopolar, tricolporate pollen grains. They
      however differ by the shape of the nectary disc, petal appendages, mericarps, and
      pollen shape and ornamentation. The new species Alatococcus siqueirae is
      described and illustrated.

PMID- 22461727
TI  - Paepalanthus rectifolius, a new name in Eriocaulaceae (Poales).
AB  - Syngonanthus weddellii var. gracilis Moldenke, (1973) was described very briefly
      based on a single collection. A careful analysis reveals that this variety has
      dimerous flowers, free petals of the pistillate flower and bifid stigmatic
      branches. It is therefore misplaced in Syngonanthus Ruhland (1900). We transfer
      it to Paepalanthus Mart. (1834) at the species level, as it is distinct from
      morphologically similar species: Paepalanthus flaccidus (Bong.) Koern. (1863),
      Paepalanthus trichophyllus (Bong.) Koern. (1863), and Paepalanthus strictus
      Koern. (1863). The epithet gracilis is no longer available, hence, we have coined
      the name Paepalanthus rectifolius. We also provide a full description,
      illustrations, a distribution map, and pertinent comments.

PMID- 22461728
TI  - Taxonomic novelties in Scapania.
AB  - Five new supraspecific taxa of Scapania are proposed, Scapania subg. Gracilidae,
      Scapania subg. Pseudomacrodiplophyllum, Scapania sect. Americanae, Scapania sect.
      Hyperboreae, and Scapania sect. Simmonsia.

PMID- 22461729
TI  - Eriocaulon madayiparense (Eriocaulaceae) - A new species from the foot hills of
      the Western Ghats of India.
AB  - Eriocaulon madayiparense Swapna, Rajesh, Manju & Prakashkumar, sp. nov. is
      described and illustrated from the Madayipara, a lateritic hillock in the midland
      of Kannur District of Kerala. The species is allied to Eriocaulon eurypeplon
      Koernicke, in its two free male and female sepals, female sepals being keeled and
      acute and not exceeding the floral bracts, acuminate leaf apex and setiform seed
      appendages appearing in vertical rows, but differs mainly in having yellow seeds
      with solitary appendage arising from transverse radial walls, curved and connate
      with the adjacent ones of the same vertical row forming longitudinal parallel
      ribs on the surface of the seeds.

PMID- 22461730
TI  - Taxonomic synopsis of invasive and native Spartina (Poaceae, Chloridoideae) in
      the Pacific Northwest (British Columbia, Washington and Oregon), including the
      first report of Spartina *townsendii for British Columbia, Canada.
AB  - Five species of the grass genus Spartina are invading salt marshes along the
      Pacific coast of North America, of which three have been documented in British
      Columbia, Canada, in only the last decade. A taxonomic synopsis of the two native
      (Spartina gracilis, Spartina pectinata) and five introduced Spartina taxa
      (Spartina anglica, Spartina alterniflora, Spartina densiflora, Spartina patens,
      Spartina *townsendii) in the Pacific Northwest is presented to facilitate their
      identification, including nomenclature, a new taxonomic key, new descriptions for
      a subset of taxa, and representative specimens. Spartina *townsendii is newly
      reported for the flora of British Columbia. The non-coastal species Spartina
      pectinata is reported from an urban site in British Columbia, the first confirmed
      report of the taxon for the province. Lectotypes are newly designated for
      Spartina anglica C.E. Hubb., Spartina maritima subvar. fallax St.-Yves, and
      Spartina cynosuroides f. major St.-Yves.

PMID- 22461731
TI  - Description and molecular diagnosis of a new species of Brunfelsia (Solanaceae)
      from the Bolivian and Argentinean Andes.
AB  - Brunfelsia plowmaniana N.Filipowicz & M.Nee sp. nov., a species from humid and
      cloud forests of the Bolivian and Argentinean Andes, is described and provided
      with a molecular diagnosis, using provisions available in the recently approved
      International Code of Nomenclature for algae, fungi and plants. Specimens
      belonging to the new species were previously placed in the polymorphic Brunfelsia
      uniflora (Pohl) D.Don, which a molecular phylogeny revealed as polyphyletic.
      Revision of numerous collections revealed clear morphological differences between
      the new species and Brunfelsia uniflora, the type locality of which is in the
      state of Sao Paulo, Brazil.

PMID- 22461732
TI  - Curvature-based environment description for robot navigation using laser range
      sensors.
AB  - This work proposes a new feature detection and description approach for mobile
      robot navigation using 2D laser range sensors. The whole process consists of two
      main modules: a sensor data segmentation module and a feature detection and
      characterization module. The segmentation module is divided in two consecutive
      stages: First, the segmentation stage divides the laser scan into clusters of
      consecutive range readings using a distance-based criterion. Then, the second
      stage estimates the curvature function associated to each cluster and uses it to
      split it into a set of straight-line and curve segments. The curvature is
      calculated using a triangle-area representation where, contrary to previous
      approaches, the triangle side lengths at each range reading are adapted to the
      local variations of the laser scan, removing noise without missing relevant
      points. This representation remains unchanged in translation or rotation, and it
      is also robust against noise. Thus, it is able to provide the same segmentation
      results although the scene will be perceived from different viewpoints.
      Therefore, segmentation results are used to characterize the environment using
      line and curve segments, real and virtual corners and edges. Real scan data
      collected from different environments by using different platforms are used in
      the experiments in order to evaluate the proposed environment description
      algorithm.

PMID- 22461741
TI  - pHLIP and acidity as a universal biomarker for cancer.
AB  - Of great importance to clinical cancer diagnosis is the use of organic
      biomarkers. The detection of RNA, DNA, and protein antigen are all established
      methods for identifying specific cancer types and instrumental in promoting
      greater survivorship of the patient. Despite many decades of intense cancer
      research, we have yet to identify a "universal" protein or nucleic acid that
      allows us to diagnose more than a small subset of cancers at a time. In this
      review, we examine the use of localized cellular acidity as a universal marker
      for solid tumors, outlining some successes with a small peptide we call pHLIP, a
      pH-sensitive biosensor that allows us to label tumor tissue in live mice.

PMID- 22461740
TI  - Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol
      homeostasis.
AB  - The LDLR family of proteins is involved in lipoproteins trafficking. While the
      role of LDLR in cardiovascular disease has been widely studied, only recently the
      role of other members of the LDLR proteins in lipoprotein homeostasis and
      atherosclerosis has emerged. LDLR, VLDLR, and LRPs bind and internalize apoE- and
      apoB-containing lipoprotein, including LDL and VLDL, and regulate their cellular
      uptake. LRP6 is a unique member of this family for its function as a co-receptor
      for Wnt signal transduction. The work in our laboratory has shown that LRP6 also
      plays a key role in lipoprotein and TG clearance, glucose homoeostasis, and
      atherosclerosis. The role of these receptor proteins in pathogenesis of diverse
      metabolic risk factors is emerging, rendering them targets of novel therapeutics
      for metabolic syndrome and atherosclerosis. This manuscript reviews the
      physiological role of the LDLR family of proteins and describes its involvement
      in pathogenesis of hyperlipidemia and atherosclerosis.

PMID- 22461739
TI  - Role of microparticles in dengue virus infection and its impact on medical
      intervention strategies.
AB  - Dengue virus (DV) is one of the most important vector-borne diseases in the
      world. It causes a disease that manifests as a spectrum of clinical symptoms,
      including dengue hemorrhagic fever. DV is proficient at diverting the immune
      system to facilitate transmission through its vector host, Aedes spp. mosquito.
      Similar to other vector-borne parasites, dengue may also require a second
      structural form, a virus of alternative morphology (VAM), to complete its life
      cycle. DV can replicate to high copy numbers in patient plasma, but no classical
      viral particles can be detected by ultra-structural microscopy analysis. A VAM
      appearing as a microparticle has been recapitulated with in vitro cell lines
      Meg01 and K562, close relatives to the cells harboring dengue virus in vivo. VAMs
      are likely to contribute to the high viremia levels observed in dengue patients.
      This review discusses the possible existence of a VAM in the DV life cycle.

PMID- 22461742
TI  - Islet transplantation in type I diabetes mellitus.
AB  - For most patients with type I diabetes, insulin therapy and glucose monitoring
      are sufficient to maintain glycemic control. However, hypoglycemia is a
      potentially lethal side effect of insulin treatment in patients who are
      glycemically labile or have hypoglycemia-associated autonomic failure [1]. For
      those patients, an alternative therapy is beta cell replacement via pancreas or
      islet transplantation. Pancreas transplants using cadaveric donor organs reduce
      insulin dependence but carry risks involved in major surgery and chronic
      immunosuppression. Islet transplantation, in which islets are isolated from donor
      pancreases and intravenously infused, require no surgery and can utilize islets
      isolated from pancreases unsuitable for whole organ transplantation. However,
      islet transplantation also requires immunosuppression, and standard steroid
      regimens may be toxic to beta cells [2]. The 2000 Edmonton Trial demonstrated the
      first long-term successful islet transplantation by using a glucocorticoid-free
      immunosuppressive regimen (sirolimus and tacrolimus). The Clinical Islet
      Transplantation (CIT) Consortium seeks to improve upon the Edmonton Protocol by
      using anti-thymocyte globulin (ATG) and TNFalpha antagonist (etanercept). The
      trials currently in progress, in addition to research efforts to find new sources
      of islet cells, reflect enormous potential for islet transplantation in treatment
      of type I diabetes.

PMID- 22461743
TI  - Guanfacine for the treatment of cognitive disorders: a century of discoveries at
      Yale.
AB  - The prefrontal cortex (PFC) is among the most evolved brain regions, contributing
      to our highest order cognitive abilities. It regulates behavior, thought, and
      emotion using working memory. Many cognitive disorders involve impairments of the
      PFC. A century of discoveries at Yale Medical School has revealed the
      neurobiology of PFC cognitive functions, as well as the molecular needs of these
      circuits. This work has led to the identification of therapeutic targets to treat
      cognitive disorders. Recent research has found that the noradrenergic alpha2A
      agonist guanfacine can improve PFC function by strengthening PFC network
      connections via inhibition of cAMP-potassium channel signaling in postsynaptic
      spines. Guanfacine is now being used to treat a variety of PFC cognitive
      disorders, including Tourette's Syndrome and Attention Deficit Hyperactivity
      Disorder (ADHD). This article reviews the history of Yale discoveries on the
      neurobiology of PFC working memory function and the identification of guanfacine
      for treating cognitive disorders.

PMID- 22461744
TI  - Mass spectrometry-based proteomics for translational research: a technical
      overview.
AB  - Mass spectrometry-based investigation of clinical samples enables the high
      throughput identification of protein biomarkers. We provide an overview of mass
      spectrometry-based proteomic techniques that are applicable to the investigation
      of clinical samples. We address sample collection, protein extraction and
      fractionation, mass spectrometry modalities, and quantitative proteomics.
      Finally, we examine the limitations and further potential of such technologies.
      Liquid chromatography fractionation coupled with tandem mass spectrometry is well
      suited to handle mixtures of hundreds or thousands of proteins. Mass spectrometry
      based proteome elucidation can reveal potential biomarkers and aid in the
      development of hypotheses for downstream investigation of the molecular
      mechanisms of disease.

PMID- 22461745
TI  - Targeted molecular imaging of angiogenesis in PET and SPECT: a review.
AB  - Over the past few decades, there have been significant advancements in the
      imaging techniques of positron emission tomography (PET) and single photon
      emission tomography (SPECT). These changes have allowed for the targeted imaging
      of cellular processes and the development of hybrid imaging systems (e.g.,
      SPECT/CT and PET/CT), which provide both functional and structural images of
      biological systems. One area that has garnered particular attention is
      angiogenesis as it relates to ischemic heart disease and limb ischemia. Though
      the aforementioned techniques have benefits and consequences, they enable
      scientists and clinicians to identify regions that are vulnerable to or have been
      exposed to ischemic injury via non-invasive means. This literature review
      highlights the advancements in molecular imaging techniques and specific probes
      as they pertain to the process of angiogenesis in cardiovascular disease.

PMID- 22461746
TI  - Getting a head start: the importance of personal genetics education in high
      schools.
AB  - With advances in sequencing technology, widespread and affordable genome
      sequencing will soon be a reality. However, studies suggest that "genetic
      literacy" of the general public is inadequate to prepare our society for this
      unprecedented access to our genetic information. As the current generation of
      high school students will come of age in an era when personal genetic information
      is increasingly utilized in health care, it is of vital importance to ensure
      these students understand the genetic concepts necessary to make informed medical
      decisions. These concepts include not only basic scientific knowledge, but also
      considerations of the ethical, legal, and social issues that will arise in the
      age of personal genomics. In this article, we review the current state of
      genetics education, highlight issues that we believe need to be addressed in a
      comprehensive genetics education curriculum, and describe our education efforts
      at the Harvard Medical School-based Personal Genetics Education Project.

PMID- 22461747
TI  - The case report in context.
AB  - Case reports are a rapid means of dissemination of information vital to the
      practice of medicine. Case reports also serve as important educational tools to
      both authors and readers. These reports often serve as a clinician's first
      experience with scholarly writing and provide an important training ground in
      manuscript preparation and publication. For readers, the case report identifies
      "recognition patterns" for rare clinical conditions and also can provide a
      thorough review on important topics related to the case. This article describes
      the components of a well-written case report for the novice writer as well as
      identifies opportunities to write a case report beyond the traditional clinical
      case report.

PMID- 22461748
TI  - Group B streptococcus mycotic aneurysm of the abdominal aorta: report of a case
      and review of the literature.
AB  - Mycotic aneurysm of the aorta is an uncommon condition, and Group B Streptococcus
      (GBS) is exceedingly rare in this setting. We present the first reported case of
      a GBS-infected abdominal aortic aneurysm (AAA) in North America. Key clinical and
      imaging findings and pathologic correlation are highlighted. A relevant review of
      the literature is discussed, which will bring the reader up to date with this
      specific disease entity.

PMID- 22461749
TI  - Decidual macrophages and their roles at the maternal-fetal interface.
AB  - The semi-allogeneic fetus, whose genome consists of maternally and paternally
      inherited alleles, must coexist with an active maternal immune system during its
      9 months in utero. Macrophages are the second most abundant immune cell at the
      maternal-fetal interface, although populations and functions for these
      populations remain ill defined. We have previously reported two distinct subsets
      of CD14(+) decidual macrophages found to be present in first trimester decidual
      tissue, 20 percent CD11c(HI) and 68 percent CD11c(LO). Interestingly, CD11c(HI)
      decidual macrophages express genes associated with lipid metabolism,
      inflammation, and antigen presentation function and specifically upregulate CD1
      molecules. Conversely, CD11c(LO) decidual macrophages express genes associated
      with extracellular matrix formation, muscle regulation, and tissue growth. The
      large abundance of CD11c(HI) decidual macrophages and their ability to process
      antigens more efficiently than CD11c(LO) macrophages suggests that CD11c(HI)
      macrophages may be important antigen processing and presenting cells at the
      maternal-fetal interface, while CD11c(LO) macrophages may perform necessary
      homeostatic functions during placental construction. Thus, macrophage
      heterogeneity may be an important and necessary division of labor that leads to
      both an induction of maternal immune cell tolerance to fetal antigens as well as
      basic homeostatic functions in human pregnancy.

PMID- 22461750
TI  - Current advances in training orthopaedic patients to comply with partial weight
      bearing instructions.
AB  - Partial weight-bearing instructions are commonly given to orthopaedic patients
      and are an important part of post-injury and/or post-operative care. However, the
      ability of patients to comply with these instructions is poorly defined. Training
      methods for instructing these patients vary widely among institutions.
      Traditional methods of training include verbal instruction and use of a bathroom
      scale. Recent technological advances have created biofeedback devices capable of
      offering feedback to partial weight-bearing patients. Biofeedback devices have
      shown great promise in training patients to better comply with partial weight
      bearing instructions. This review examines the background and significance of
      partial weight bearing and offers insights into current advances in training
      methods for partial weight-bearing patients.

PMID- 22461751
TI  - The complication of coinfection.
AB  - Infectious disease remains one of the largest burdens on humankind. Even with
      modern medical and public health standards, infectious disease remained the No. 1
      killer worldwide at the turn of the century. Often, the most costly disease
      burdens come from multiple infections at once, i.e., coinfection. Influenza, an
      annual infection often considered relatively harmless, can increase
      susceptibility to both deadly bacterial pneumonia and childhood ear infections.
      Major health threat HIV rarely kills a patient on its own, but instead allows for
      opportunistic infections and re-emergence of infections such as tuberculosis.
      What generates these unique relationships is not well understood; herein, we
      examine in detail three types of coinfection and the unique interactions between
      infectious agents as well as with the host in each setting. We also begin to
      address how we may aid further understanding of coinfection and what questions
      need to be addressed to help direct future treatments.

PMID- 22461752
TI  - Etiology of sarcoidosis: does infection play a role?
AB  - Sarcoidosis is a granulomatous inflammatory disorder of unclear etiology, which
      is known to affect multiple organ systems including the lungs, heart, skin,
      central nervous system, and eyes, among others. For this reason, sarcoidosis
      represents a systemic medical disorder that is clinically relevant to multiple
      medical sub-specialties. Despite extensive research, the etiology of sarcoidosis
      has yet to be elucidated, although most evidence supports that the pathogenetic
      mechanism of sarcoidosis is an aberrant immune response, driven by an
      unidentified antigen (or antigens) in genetically susceptible individuals.
      Multiple candidate etiologic agents, including microbial organisms and
      environmental agents, have been investigated, but study results are inconclusive.
      In this review, we describe the known histologic and immunologic features of
      sarcoidosis and discuss the evidence supporting a role for infectious processes
      in the pathogenesis of sarcoidosis.

PMID- 22461753
TI  - Creating a surgery clerkship in a changing environment: reality, simulation, and
      the rules of engagement.
AB  - This review describes the current challenges associated with creating a
      successful surgical clerkship and the ways in which teacher-focused and
      curriculum-focused initiatives can address these challenges. The challenges are
      both systemic (reflected by changes in our health care system and training
      programs) and institutional (reflected by factors that affect curriculum design
      and faculty advancement). Particular attention is paid to residents as teachers,
      faculty as mentors, the educational impact of the operating room, and the role of
      simulation. Strategies for engaging students, residents, and faculty are
      explored. The premise and impact of a comprehensive simulation course on the
      clinical education of medical students is detailed. Emphasis is placed on the
      educational validity of accountability and engagement of both the teachers and
      the learners.

PMID- 22461754
TI  - Antidepressants and advertising: psychopharmaceuticals in crisis.
AB  - As the efficacy and science of psychopharmaceuticals has become increasingly
      uncertain, marketing of these drugs to both physicians and consumers continues to
      a central part of a multi-billion dollar per year industry in the United States.
      We explore how such drug marketing portrays idealized scientific relationships
      between psychopharmaceuticals and depression; how multiple stakeholders,
      including scientists, regulatory agencies, and patient advocacy groups, negotiate
      neurobiological explanations of mental illness; and how the placebo effect has
      become a critical issue in these debates, including the possible role of drug
      advertising to influence the placebo effect directly. We argue that if and how
      antidepressants "work" is not a straightforward objective question, but rather a
      larger social contest involving scientific debate, the political history of the
      pharmaceutical industry, cultural discourses surrounding the role of drugs in
      society, and the interpretive flexibility of personal experience.

PMID- 22461755
TI  - Residential radon appears to prevent lung cancer.
AB  - Residential radon has been found to be associated with lung cancer in
      epidemiological/ecological studies and the researchers have inappropriately
      concluded that residential radon causes lung cancer. Their conclusion relates to
      the linear-no-threshold (LNT) hypothesis-based, risk-assessment paradigm;
      however, the LNT hypothesis has been invalidated in numerous studies. It is shown
      in this paper that our hormetic relative risk (HRR) model is consistent with lung
      cancer data where detailed measurements of radon in each home were carried out.
      Based on the HRR model, low-level radon radioactive progeny is credited for
      activated natural protection (ANP) against lung cancer including smoking-related
      lung cancer. The proportion B(x) (benefit function) of ANP beneficiaries
      increases as the average radon level x increases to near the Environmental
      Protection Agency's action level of 4 picocuries/L (approximately 150 Bq m(-3)).
      As the average level of radon increases to somewhat above the action level, ANP
      beneficiaries progressively decrease to zero (B(x) decreases to 0), facilitating
      the occurrence of smoking-related lung cancers as well as those related to other
      less important risk factors. Thus, residential radon does not appear to cause
      lung cancer but rather to protect, in an exposure-level-dependent manner, from
      its induction by other agents (e.g., cigarette-smoke-related carcinogens).

PMID- 22461756
TI  - Radiation worker protection by exposure scheduling.
AB  - The discovery of the protective adaptive response of cells to a low dose of
      radiation suggests applications to radiation worker/first responder protection.
      Its use in cancer radiotherapy has been discussed in a separate publication. This
      paper describes simple changes in scheduling that can make use of these
      beneficial adaptive effects for protection. No increase in total exposure is
      necessary, only a simple change in the timing of radiation exposure. A low dose
      of radiation at a sufficient dose rate will trigger the adaptive response. This
      in turn will offer a considerable protection against the damage from a subsequent
      high dose. A simple scenario is discussed as well as a brief review of the
      experimental basis of the adaptive response.

PMID- 22461757
TI  - Thyroid cancer after chernobyl: obfuscated truth.

PMID- 22461758
TI  - A stochastic markov model of cellular response to radiation.
AB  - A stochastic model based on the Markov Chain Monte Carlo process is used to
      describe responses to ionizing radiation in a group of cells. The results show
      that where multiple relationships linearly depending on the dose are introduced,
      the overall reaction shows a threshold, and, generally, a non-linear response.
      Such phenomena have been observed and reported in a number of papers. The present
      model permits the inclusion of adaptive responses and bystander effects that can
      lead to hormetic effects. In addition, the model allows for incorporating various
      time-dependent phenomena. Essentially, all known biological effects can be
      reproduced using the proposed model.

PMID- 22461759
TI  - On ecological studies: a short communication.
AB  - The typical objective of research is to try and identify cause-and-effect
      relationships. As with any research design, there are strengths and weaknesses
      involved in trying to achieve this objective. Some study designs are stronger
      than others in attempting to establish cause-and-effect associations. The task of
      establishing cause-and-effect relationships is challenging (Hill, 1965) and any
      study that does not include experimentation, that is by manipulating a variable's
      exposure, is inhibited from drawing causal inferences (Heath, 1995). Similarly,
      statistical significance is also based on probability rather than certainty. This
      article focuses on a particular research design, namely, the ecological study,
      and attempts to serve as a reminder that the design has its place in the realm of
      various research designs.

PMID- 22461760
TI  - Human Lung Cancer Risks from Radon - Part II - Influence from Combined Adaptive
      Response and Bystander Effects - A Microdose Analysis.
AB  - In the prior Part I, the potential influence of the low level alpha radiation
      induced bystander effect (BE) on human lung cancer risks was examined. Recent
      analysis of adaptive response (AR) research results with a Microdose Model has
      shown that single low LET radiation induced charged particles traversals through
      the cell nucleus activates AR. We have here conducted an analysis based on what
      is presently known about adaptive response and the bystander effect (BE) and what
      new research is needed that can assist in the further evaluation human cancer
      risks from radon. We find that, at the UNSCEAR (2000) worldwide average human
      exposures from natural background and man-made radiations, the human lung
      receives about a 25% adaptive response protection against the radon alpha
      bystander damage. At the UNSCEAR (2000) minimum range of background exposure
      levels, the lung receives minimal AR protection but at higher background levels,
      in the high UNSCEAR (2000) range, the lung receives essentially 100% protection
      from both the radon alpha damage and also the endogenic, spontaneously occurring,
      potentially carcinogenic, lung cellular damage.

PMID- 22461761
TI  - Effects of streptolysin o on extracellular matrix gene expression in normal human
      epidermal keratinocytes.
AB  - ML-05 is a non-hemolytic form of streptolysin O, the membrane-damaging
      extracellular toxin produced by certain streptococci. ML-05 stimulates
      keratinocyte migration and proliferation in wound-healing scratch assays and
      promotes wound healing in a human skin organ culture wound model. Pathway-focused
      DNA microarrays were used to elucidate ML-05's mechanism of action in wound
      healing processes. Normal human epidermal keratinocytes (NHEK) were treated with
      varying concentrations of ML-05 for 24 hours, followed by RNA extraction and cRNA
      production. Gene expression profiling utilized microarrays containing nucleic
      acid probes for 113 extracellular matrix (ECM) genes. Microarrays yielded 6
      upregulated and 4 downregulated genes with >=2-fold changes and p<0.05 in t
      tests. Quantitative real-time polymerase chain reactions (qPCR) were used to
      verify gene regulation. Upregulated genes of interest were VCAN (formerly CSPG2,
      encoding versican), CD44 (encoding hyaluronan receptor), ICAM1 (encoding
      intercellular adhesion molecule-1) and CTGF (encoding connective tissue growth
      factor). All four upregulated genes encode proteins involved in promoting
      keratinocyte migration and proliferation. Downregulated genes of interest were
      MMP9 (encoding matrix metalloproteinase 9) and SPP1 (encoding osteopontin). ML-05
      may enhance wound healing through the expression of specific genes encoding
      proteins capable of promoting keratinocyte migration, proliferation, and other
      activities related to maintaining ECM structure and function.

PMID- 22461762
TI  - Modeling DNA double-strand break repair kinetics as an epiregulated cell
      community-wide (epicellcom) response to radiation stress.
AB  - The multicellular signaling model (MULTISIG1) was recently introduced to simulate
      the kinetics of repair of DNA double-strand breaks (DSBs) that were induced in
      confluent (non-dividing) cultured cells by a very low radiation dose where at
      most a single induced DSB would be expected in a given cell nucleus. The repair
      kinetics was modeled as representing what is now called an epigenetically
      regulated (epiregulated) cell-community-wide (epicellcom) response to radiation
      stress. DSB repair initiation is assumed to require a threshold number of cells
      with DSBs participating in intercellular stress-response signaling. The MULTISIG1
      model is extended in this study to apply to moderate doses where several DSBs can
      occur on the same DNA molecule. The repair of multiple breaks on the same
      molecule is treated as sequential stochastic events. For cells of differing
      genetic characteristics and epigenetic statuses, relationships are provided for
      evaluating the relative susceptibility (RS) for DSB induction, relative repair
      capacity (RRC) for DSB repair, and relative epiapoptosis capacity (REC), for
      epigenetically regulated apoptosis. The modified MULTISIG1 model is used to
      characterize the expected repair kinetics for confluent, human lung fibroblasts
      (MRC-5 line) briefly exposed in vitro to 90-kV x-rays. Possible application of
      the model to biological dosimetry is also discussed.

PMID- 22461764
TI  - Deadly radon in montana?

PMID- 22461763
TI  - Biphasic dose response in low level light therapy - an update.
AB  - Low-level laser (light) therapy (LLLT) has been known since 1967 but still
      remains controversial due to incomplete understanding of the basic mechanisms and
      the selection of inappropriate dosimetric parameters that led to negative
      studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown
      both in vitro studies and in animal experiments. This review will provide an
      update to our previous (Huang et al. 2009) coverage of this topic. In vitro
      mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane
      potential show biphasic patterns, while others such as mitochondrial reactive
      oxygen species show a triphasic dose-response with two distinct peaks. The Janus
      nature of reactive oxygen species (ROS) that may act as a beneficial signaling
      molecule at low concentrations and a harmful cytotoxic agent at high
      concentrations, may partly explain the observed responses in vivo. Transcranial
      LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern
      with peaks in beneficial neurological effects observed when the number of
      treatments is varied, and when the energy density of an individual treatment is
      varied. Further understanding of the extent to which biphasic dose responses
      apply in LLLT will be necessary to optimize clinical treatments.

PMID- 22461765
TI  - The bird of time: cognition and the avian biological clock.
AB  - Avian behavior and physiology are embedded in time at many levels of biological
      organization. Biological clock function in birds is critical for sleep/wake
      cycles, but may also regulate the acquisition of place memory, learning of song
      from tutors, social integration, and time-compensated navigation. This
      relationship has two major implications. First, mechanisms of the circadian clock
      should be linked in some way to the mechanisms of all these behaviors. How is not
      yet clear, and evidence that the central clock has effects is piecemeal. Second,
      selection acting on characters that are linked to the circadian clock should
      influence aspects of the clock mechanism itself. Little evidence exists for this
      in birds, but there have been few attempts to assess this idea. At its core, the
      avian circadian clock is a multi-oscillator system comprising the pineal gland,
      the retinae, and the avian homologs of the suprachiasmatic nuclei, whose mutual
      interactions ensure coordinated physiological functions, which are in turn
      synchronized to ambient light cycles (LD) via encephalic, pineal, and retinal
      photoreceptors. At the molecular level, avian biological clocks comprise a
      genetic network of "positive elements" clock and bmal1 whose interactions with
      the "negative elements" period 2 (per2), period 3 (per3), and the cryptochromes
      form an oscillatory feedback loop that circumnavigates the 24 h of the day. We
      assess the possibilities for dual integration of the clock with time-dependent
      cognitive processes. Closer examination of the molecular, physiological, and
      behavioral elements of the circadian system would place birds at a very
      interesting fulcrum in the neurobiology of time in learning, memory, and
      navigation.

PMID- 22461766
TI  - Calcium-activated chloride current expression in axotomized sensory neurons: what
      for?
AB  - Calcium-activated chloride currents (CaCCs) are activated by an increase in
      intracellular calcium concentration. Peripheral nerve injury induces the
      expression of CaCCs in a subset of adult sensory neurons in primary culture
      including mechano- and proprioceptors, though not nociceptors. Functional
      screenings of potential candidate genes established that Best1 is a molecular
      determinant for CaCC expression among axotomized sensory neurons, while Tmem16a
      is acutely activated by inflammatory mediators in nociceptors. In nociceptors,
      such CaCCs are preferentially activated under receptor-induced calcium
      mobilization contributing to cell excitability and pain. In axotomized mechano-
      and proprioceptors, CaCC activation does not promote electrical activity and
      prevents firing, a finding consistent with electrical silencing for growth
      competence of adult sensory neurons. In favor of a role in the process of neurite
      growth, CaCC expression is temporally correlated to neurons displaying a
      regenerative mode of growth. This perspective focuses on the molecular identity
      and role of CaCC in axotomized sensory neurons and the future directions to
      decipher the cellular mechanisms regulating CaCC during neurite (re)growth.

PMID- 22461767
TI  - Trans-acting factors governing acetylcholinesterase mRNA metabolism in neurons.
AB  - The most characterized function of acetylcholinesterase (AChE) is to terminate
      cholinergic signaling at neuron-neuron and neuro-muscular synapses. In addition,
      AChE is causally or casually implicated in neuronal development, stress-response,
      cognition, and neurodegenerative diseases. Given the importance of AChE, many
      studies have focused on identifying the molecular mechanisms that govern its
      expression. Despite these efforts, post-transcriptional control of AChE mRNA
      expression is still relatively unclear. Here, we review the trans-acting factors
      and cis-acting elements that are known to control AChE pre-mRNA splicing, mature
      mRNA stability and translation. Moreover, since the Hu/ELAV family of RNA-binding
      proteins (RBPs) have emerged in recent years as "master" post-transcriptional
      regulators, we discuss the possibility that predominantly neuronal ELAVs (nELAVs)
      play multiple roles in regulating splicing, stability, localization, and
      translation of AChE mRNA.

PMID- 22461768
TI  - Co-Release of GABA Does Not Occur at Glycinergic Synapses onto Lumbar Motoneurons
      in Juvenile Mice.
AB  - The fast inhibitory neurotransmitters glycine and GABA are co-localized in
      synaptic terminals of inhibitory interneurons in the spinal cord and co-released
      onto lumbar motoneurons in neonatal rats. We performed whole-cell voltage-clamp
      experiments on spinal cord preparations obtained from juvenile (P8-14) mice to
      determine whether inhibitory currents exhibited GABAergic components in
      motoneurons of animals of weight-bearing age. Subsequently we established whether
      or not GABA is co-released at glycinergic synapses onto motoneurons by
      determining if it conferred modulatory effects on the kinetics of glycinergic
      currents. Exponential fitting analysis showed that evoked and miniature
      inhibitory post-synaptic currents (IPSCs) were best-fitted with a single decay
      time constant. Responses recorded from connected interneuron-motoneuron pairs
      showed no effect of a benzodiazepine or a GABA(A) receptor antagonist. Similarly
      IPSCs evoked by extracellular stimulation and miniature IPSCs were not affected
      by either agent, indicating the absence of co-detection. Experimental
      manipulation of the relative content of pre-synaptic GABA and glycine conferred
      no effect on post-synaptic responses. It is thus unlikely that GABA is co
      released in biologically relevant amounts at glycinergic synapses onto lumbar
      motoneurons in mice of this age.

PMID- 22461769
TI  - Neuronal encoding of object and distance information: a model simulation study on
      naturalistic optic flow processing.
AB  - We developed a model of the input circuitry of the FD1 cell, an identified motion
      sensitive interneuron in the blowfly's visual system. The model circuit
      successfully reproduces the FD1 cell's most conspicuous property: its larger
      responses to objects than to spatially extended patterns. The model circuit also
      mimics the time-dependent responses of FD1 to dynamically complex naturalistic
      stimuli, shaped by the blowfly's saccadic flight and gaze strategy: the FD1
      responses are enhanced when, as a consequence of self-motion, a nearby object
      crosses the receptive field during intersaccadic intervals. Moreover, the model
      predicts that these object-induced responses are superimposed by pronounced
      pattern-dependent fluctuations during movements on virtual test flights in a
      three-dimensional environment with systematic modifications of the environmental
      patterns. Hence, the FD1 cell is predicted to detect not unambiguously objects
      defined by the spatial layout of the environment, but to be also sensitive to
      objects distinguished by textural features. These ambiguous detection abilities
      suggest an encoding of information about objects-irrespective of the features by
      which the objects are defined-by a population of cells, with the FD1 cell
      presumably playing a prominent role in such an ensemble.

PMID- 22461770
TI  - Two-photon scanning microscopy of in vivo sensory responses of cortical neurons
      genetically encoded with a fluorescent voltage sensor in rat.
AB  - A fluorescent voltage sensor protein "Flare" was created from a Kv1.4 potassium
      channel with YFP situated to report voltage-induced conformational changes in
      vivo. The RNA virus Sindbis introduced Flare into neurons in the binocular region
      of visual cortex in rat. Injection sites were selected based on intrinsic optical
      imaging. Expression of Flare occurred in the cell bodies and dendritic processes.
      Neurons imaged in vivo using two-photon scanning microscopy typically revealed
      the soma best, discernable against the background labeling of the neuropil.
      Somatic fluorescence changes were correlated with flashed visual stimuli;
      however, averaging was essential to observe these changes. This study
      demonstrates that the genetic modification of single neurons to express a
      fluorescent voltage sensor can be used to assess neuronal activity in vivo.

PMID- 22461771
TI  - Olfactory aversive conditioning alters olfactory bulb mitral/tufted cell
      glomerular odor responses.
AB  - The anatomical organization of receptor neuron input into the olfactory bulb (OB)
      allows odor information to be transformed into an odorant-specific spatial map of
      mitral/tufted (M/T) cell glomerular activity at the upper level of the OB. In
      other sensory systems, neuronal representations of stimuli can be reorganized or
      enhanced following learning. While the mammalian OB has been shown to undergo
      experience-dependent plasticity at the glomerular level, it is still unclear if
      similar representational change occurs within (M/T) cell glomerular odor
      representations following learning. To address this, odorant-evoked glomerular
      activity patterns were imaged in mice expressing a GFP-based calcium indicator
      (GCaMP2) in OB (M/T) cells. Glomerular odor responses were imaged before and
      after olfactory associative conditioning to aversive foot shock. Following
      conditioning, we found no overall reorganization of the glomerular
      representation. Training, however, did significantly alter the amplitudes of
      individual glomeruli within the representation in mice in which the odor was
      presented together with foot shock. Further, the specific pairing of foot shock
      with odor presentations lead to increased responses primarily in initially weakly
      activated glomeruli. Overall, these results suggest that associative conditioning
      can enhance the initial representation of odors within the OB by enhancing
      responses to the learned odor in some glomeruli.

PMID- 22461772
TI  - Behavioral resilience in the post-genomic era: emerging models linking genes with
      environment.
AB  - One of the most important deliverables of the post-genomic era has been a new and
      nuanced appreciation of how the environment shapes-and holds potential to alter
      the expression of susceptibility genes for behavioral dimensions and disorders.
      This paper will consider three themes that have emerged from cutting-edge
      research studies that utilize newer molecular genetic approaches as well as tried
      and-true genetic epidemiological methodologies, with particular reference to
      evolving perspectives on resilience and plasticity. These themes are: (1)
      evidence for replicable and robust shared environmental effects on a number of
      clinically relevant behaviors in childhood and adolescence; (2) evolving research
      on gene-environment interaction; and (3) a newer focus on differential
      susceptibility and plasticity. The net sum of these themes is that consideration
      of genetic effects on behavioral dimensions and disorders needs to be connected
      to thinking about the role of environment as a potent source for promoting
      resilience and change.

PMID- 22461773
TI  - Ambiguous figures - what happens in the brain when perception changes but not the
      stimulus.
AB  - During observation of ambiguous figures our perception reverses spontaneously
      although the visual information stays unchanged. Research on this phenomenon so
      far suffered from the difficulty to determine the instant of the endogenous
      reversals with sufficient temporal precision. A novel experimental paradigm with
      discontinuous stimulus presentation improved on previous temporal estimates of
      the reversal event by a factor of three. It revealed that disambiguation of
      ambiguous visual information takes roughly 50 ms or two loops of recurrent neural
      activity. Further, the decision about the perceptual outcome has taken place at
      least 340 ms before the observer is able to indicate the consciously perceived
      reversal manually. We provide a short review about physiological studies on
      multistable perception with a focus on electrophysiological data. We further
      present a new perspective on multistable perception that can easily integrate
      previous apparently contradicting explanatory approaches. Finally we propose
      possible extensions toward other research fields where ambiguous figure
      perception may be useful as an investigative tool.

PMID- 22461774
TI  - Mind-body relationships in elite apnea divers during breath holding: a study of
      autonomic responses to acute hypoxemia.
AB  - The mental control of ventilation with all associated phenomena, from relaxation
      to modulation of emotions, from cardiovascular to metabolic adaptations,
      constitutes a psychophysiological condition characterizing voluntary breath
      holding (BH). BH induces several autonomic responses, involving both autonomic
      cardiovascular and cutaneous pathways, whose characterization is the main aim of
      this study. Electrocardiogram and skin conductance (SC) recordings were collected
      from 14 elite divers during three conditions: free breathing (FB), normoxic phase
      of BH (NPBH) and hypoxic phase of BH (HPBH). Thus, we compared a set of features
      describing signal dynamics between the three experimental conditions: from heart
      rate variability (HRV) features (in time and frequency-domains and by using
      nonlinear methods) to rate and shape of spontaneous SC responses (SCRs). The main
      result of the study rises by applying a Factor Analysis to the subset of features
      significantly changed in the two BH phases. Indeed, the Factor Analysis allowed
      to uncover the structure of latent factors which modeled the autonomic response:
      a factor describing the autonomic balance (AB), one the information increase rate
      (IIR), and a latter the central nervous system driver (CNSD). The BH did not
      disrupt the FB factorial structure, and only few features moved among factors.
      Factor Analysis indicates that during BH (1) only the SC described the emotional
      output, (2) the sympathetic tone on heart did not change, (3) the dynamics of
      interbeats intervals showed an increase of long-range correlation that
      anticipates the HPBH, followed by a drop to a random behavior. In conclusion,
      data show that the autonomic control on heart rate and SC are differentially
      modulated during BH, which could be related to a more pronounced effect on
      emotional control induced by the mental training to BH.

PMID- 22461775
TI  - DISC1 Pathway in Brain Development: Exploring Therapeutic Targets for Major
      Psychiatric Disorders.
AB  - Genetic risk factors for major psychiatric disorders play key roles in
      neurodevelopment. Thus, exploring the molecular pathways of risk genes is
      important not only for understanding the molecular mechanisms underlying brain
      development, but also to decipher how genetic disturbances affect brain
      maturation and functioning relevant to major mental illnesses. During the last
      decade, there has been significant progress in determining the mechanisms whereby
      risk genes impact brain development. Nonetheless, given that the majority of
      psychiatric disorders have etiological complexities encompassing multiple risk
      genes and environmental factors, the biological mechanisms of these diseases
      remain poorly understood. How can we move forward to our research for discovery
      of the biological markers and novel therapeutic targets for major mental
      disorders? Here we review recent progress in the neurobiology of disrupted in
      schizophrenia 1 (DISC1), a major risk gene for major mental disorders, with a
      particular focus on its roles in cerebral cortex development. Convergent findings
      implicate DISC1 as part of a large, multi-step pathway implicated in various
      cellular processes and signal transduction. We discuss links between the DISC1
      pathway and environmental factors, such as immune/inflammatory responses, which
      may suggest novel therapeutic targets. Existing treatments for major mental
      disorders are hampered by a limited number of pharmacological targets.
      Consequently, elucidation of the DISC1 pathway, and its association with
      neuropsychiatric disorders, may offer hope for novel treatment interventions.

PMID- 22461776
TI  - How to Begin to Overcome the Ambiguity Present in Differentiation between
      Contents and Levels of Consciousness?
AB  - Recently, a welcome trend has emerged - in addition to the traditional studies on
      contents and states of consciousness, levels of consciousness have become a
      matter of research. However, there are some conceptual and methodological
      difficulties with this research - the labels used for empirical measurement of
      levels are ambiguous and underspecified while the research on neural correlates
      of consciousness has not been well linked to psychophysical approaches to
      studying the levels of consciousness. This article suggests a perspective on how
      to advance the psychophysics of measuring the levels by precisely specifying
      level-specific contents and how to relate the distinction between contents and
      levels to the distinction between the underlying brain mechanisms necessary for
      processing contents and regulating the level of consciousness.

PMID- 22461777
TI  - Recognition of social identity in ants.
AB  - Recognizing the identity of others, from the individual to the group level, is a
      hallmark of society. Ants, and other social insects, have evolved advanced
      societies characterized by efficient social recognition systems. Colony identity
      is mediated by colony specific signature mixtures, a blend of hydrocarbons
      present on the cuticle of every individual (the "label"). Recognition occurs when
      an ant encounters another individual, and compares the label it perceives to an
      internal representation of its own colony odor (the "template"). A mismatch
      between label and template leads to rejection of the encountered individual.
      Although advances have been made in our understanding of how the label is
      produced and acquired, contradictory evidence exists about information processing
      of recognition cues. Here, we review the literature on template acquisition in
      ants and address how and when the template is formed, where in the nervous system
      it is localized, and the possible role of learning. We combine seemingly
      contradictory evidence in to a novel, parsimonious theory for the information
      processing of nestmate recognition cues.

PMID- 22461778
TI  - Effects of Temporal Features and Order on the Apparent duration of a Visual
      Stimulus.
AB  - The apparent duration of a visual stimulus has been shown to be influenced by its
      speed. For low speeds, apparent duration increases linearly with stimulus speed.
      This effect has been ascribed to the number of changes that occur within a visual
      interval. Accordingly, a higher number of changes should produce an increase in
      apparent duration. In order to test this prediction, we asked subjects to compare
      the relative duration of a 10-Hz drifting comparison stimulus with a standard
      stimulus that contained a different number of changes in different conditions.
      The standard could be static, drifting at 10 Hz, or mixed (a combination of
      variable duration static and drifting intervals). In this last condition the
      number of changes was intermediate between the static and the continuously
      drifting stimulus. For all standard durations, the mixed stimulus looked
      significantly compressed (~20% reduction) relative to the drifting stimulus.
      However, no difference emerged between the static (that contained no changes) and
      the mixed stimuli (which contained an intermediate number of changes). We also
      observed that when the standard was displayed first, it appeared compressed
      relative to when it was displayed second with a magnitude that depended on
      standard duration. These results are at odds with a model of time perception that
      simply reflects the number of temporal features within an interval in determining
      the perceived passing of time.

PMID- 22461780
TI  - Access to Expert Stroke Care with Telemedicine: REACH MUSC.
AB  - Stroke is a leading cause of death and disability, and recombinant tissue
      plasminogen activator (rtPA) can significantly reduce the long-term impact of
      acute ischemic stroke (AIS) if given within 3 h of symptom onset. South Carolina
      is located in the "stroke belt" and has a high rate of stroke and stroke
      mortality. Many small rural SC hospitals do not maintain the expertise needed to
      treat AIS patients with rtPA. MUSC is an academic medical center using REACH MUSC
      telemedicine to deliver stroke care to 15 hospitals in the state, increasing the
      likelihood of timely treatment with rtPA. The purpose of this study is to
      determine the increase in access to rtPA through the use of telemedicine for AIS
      in the general population and in specific segments of the population based on
      age, gender, race, ethnicity, education, urban/rural residence, poverty, and
      stroke mortality. We used a retrospective cross-sectional design examining Census
      data from 2000 and geographic information systems analysis to identify South
      Carolina residents that live within 30 or 60 min of a primary stroke center (PSC)
      or a REACH MUSC site. We include all South Carolina citizens in our analysis and
      specifically examine the population's age, gender, race, ethnicity, education,
      urban/rural residence, poverty, and stroke mortality. Our sample includes
      4,012,012 South Carolinians. The main measure is access to expert stroke care at
      a PSC or a REACH MUSC hospital within 30 or 60 min. We find that without REACH
      MUSC, only 38% of the population has potential access to expert stroke care in SC
      within 60 min given that most PSCs will maintain expert stroke coverage. REACH
      MUSC allows 76% of the population to be within 60 min of expert stroke care, and
      43% of the population to be within 30 min drive time of expert stroke care. These
      increases in access are especially significant for groups that have faced
      disparities in care and high rates of AIS. The use of telemedicine can greatly
      increase access to care for residents throughout South Carolina.

PMID- 22461779
TI  - Neuromuscular manifestations of west nile virus infection.
AB  - The most common neuromuscular manifestation of West Nile virus (WNV) infection is
      a poliomyelitis syndrome with asymmetric paralysis variably involving one
      (monoparesis) to four limbs (quadriparesis), with or without brainstem
      involvement and respiratory failure. This syndrome of acute flaccid paralysis may
      occur without overt fever or meningoencephalitis. Although involvement of
      anterior horn cells in the spinal cord and motor neurons in the brainstem are the
      major sites of pathology responsible for neuromuscular signs, inflammation also
      may involve skeletal or cardiac muscle (myositis, myocarditis), motor axons
      (polyradiculitis), and peripheral nerves [Guillain-Barre syndrome (GBS), brachial
      plexopathy]. In addition, involvement of spinal sympathetic neurons and ganglia
      provides an explanation for autonomic instability seen in some patients. Many
      patients also experience prolonged subjective generalized weakness and disabling
      fatigue. Despite recent evidence that WNV may persist long-term in the central
      nervous system or periphery in animals, the evidence in humans is controversial.
      WNV persistence would be of great concern in immunosuppressed patients or in
      those with prolonged or recurrent symptoms. Support for the contention that WNV
      can lead to autoimmune disease arises from reports of patients presenting with
      various neuromuscular diseases that presumably involve autoimmune mechanisms
      (GBS, other demyelinating neuropathies, myasthenia gravis, brachial plexopathies,
      stiff-person syndrome, and delayed or recurrent symptoms). Although there is no
      specific treatment or vaccine currently approved in humans, and the standard
      remains supportive care, drugs that can alter the cascade of immunobiochemical
      events leading to neuronal death may be potentially useful (high-dose
      corticosteroids, interferon preparations, and intravenous immune globulin
      containing WNV-specific antibodies). Human experience with these agents seems
      promising based on anecdotal reports.

PMID- 22461781
TI  - IRES-Dependent Translational Control during Virus-Induced Endoplasmic Reticulum
      Stress and Apoptosis.
AB  - Many virus infections and stresses can induce endoplasmic reticulum (ER) stress
      response, a host self-defense mechanism against viral invasion and stress. During
      this event, viral and cellular gene expression is actively regulated and often
      encounters a switching of the translation initiation from cap-dependent to
      internal ribosome-entry sites (IRES)-dependent. This switching is largely
      dependent on the mRNA structure of the 5' untranslated region (5' UTR) and on the
      particular stress stimuli. Picornaviruses and some other viruses contain IRESs
      within their 5' UTR of viral genome and employ an IRES-driven mechanism for
      translation initiation. Recently, a growing number of cellular genes involved in
      growth control, cell cycle progression and apoptosis were also found to contain
      one or more IRES within their long highly structured 5' UTRs. These genes
      initiate translation usually by a cap-dependent mechanism under normal
      physiological conditions; however, in certain environments, such as infection,
      starvation, and heat shock they shift translation initiation to an IRES-dependent
      modality. Although the molecular mechanism is not entirely understood, a number
      of studies have revealed that several cellular biochemical processes are
      responsible for the switching of translation initiation to IRES-dependent. These
      include the cleavage of translation initiation factors by viral and/or host
      proteases, phosphorylation (inactivation) of host factors for translation
      initiation, overproduction of homologous proteins of cap-binding protein
      eukaryotic initiation factors (eIF)4E, suppression of cap-binding protein eIF4E
      expression by specific microRNA, activation of enzymes for mRNA decapping, as
      well as others. Here, we summarize the recent advances in our understanding of
      the molecular mechanisms for the switching of translation initiation,
      particularly for the proteins involved in cell survival and apoptosis in the ER
      stress pathways during viral infections.

PMID- 22461782
TI  - SCCmec Type IX Element in Methicillin Resistant Staphylococcusaureusspa Type t337
      (CC9) Isolated from Pigs and Pork in Thailand.
AB  - Methicillin resistant Staphylococcusaureus (MRSA) have emerged among livestock in
      several countries. In this study, we describe the results of a screening
      performed in pigs and raw pork samples in Thailand. Ten pork samples and 15 nasal
      swabs from pigs were collected from 2 markets and 1 pig farm in the Samuth
      Songkhram province in Thailand. MRSA were isolated using selective isolation
      procedures and confirmed by mecA PCR. The MRSA were characterized by
      antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE),
      spa typing, SCCmec typing, and MLST. Resistance and virulence markers were
      screened using a microarray. Five of the pork samples and six pig nasal swabs
      were positive for MRSA. All 11 isolates belonged to spa type t337 but showed
      diversity in antimicrobial resistance patterns and PFGE profiles. Additionally,
      the isolates were sequence-typed; ST9, ST2136, ST2278 belonging to the clonal
      complex; CC9. All isolates harbored SCCmec IX and were resistant to 7 out of 14
      tested antimicrobials; additional resistances to all antimicrobials tested were
      found in some of the pork and pig isolates and 1 pork isolate was resistant to 13
      antimicrobials tested. Microarray analysis identified blaZ, aac-aphD, vga(A),
      tetM, and a tet efflux marker, in all strains and additionally ermB and aadD, cat
      and fex(A) in the pork isolates. None of the isolates were found PVL-positive,
      but enterotoxins were identified in all isolates. To our knowledge, only a few
      descriptions of MRSA in livestock and food products in Thailand have been
      observed but this is the first observation of MRSA CC9 associated with SCCmec IX
      in pork. This study indicates a likely widespread distribution of MRSA in pig and
      pork in Thailand and further investigation on the prevalence and importance of
      livestock associated MRSA in Thailand is needed.

PMID- 22461783
TI  - Increased levels of multiresistant bacteria and resistance genes after wastewater
      treatment and their dissemination into lake geneva, Switzerland.
AB  - At present, very little is known about the fate and persistence of multiresistant
      bacteria (MRB) and their resistance genes in natural aquatic environments.
      Treated, but partly also untreated sewage of the city of Lausanne, Switzerland is
      discharged into Vidy Bay (Lake Geneva) resulting in high levels of contamination
      in this part of the lake. In the present work we have studied the prevalence of
      MRB and resistance genes in the wastewater stream of Lausanne. Samples from
      hospital and municipal raw sewage, treated effluent from Lausanne's wastewater
      treatment plant (WTP) as well as lake water and sediment samples obtained close
      to the WTP outlet pipe and a remote site close to a drinking water pump were
      evaluated for the prevalence of MRB. Selected isolates were identified (16S rRNA
      gene fragment sequencing) and characterized with regards to further resistances,
      resistance genes, and plasmids. Mostly, studies investigating this issue have
      relied on cultivation-based approaches. However, the limitations of these tools
      are well known, in particular for environmental microbial communities, and
      cultivation-independent molecular tools should be applied in parallel in order to
      take non-culturable organisms into account. Here we directly quantified the
      sulfonamide resistance genes sul1 and sul2 from environmental DNA extracts using
      TaqMan real-time quantitative PCR. Hospital sewage contained the highest load of
      MRB and antibiotic resistance genes (ARGs). Wastewater treatment reduced the
      total bacterial load up to 78% but evidence for selection of extremely
      multiresistant strains and accumulation of resistance genes was observed. Our
      data clearly indicated pollution of sediments with ARGs in the vicinity of the
      WTP outlet. The potential of lakes as reservoirs of MRB and potential risks are
      discussed.

PMID- 22461784
TI  - Regular Multivitamin Supplement Use, Single Nucleotide Polymorphisms in ATIC,
      SHMT2, and SLC46A1, and Risk of Ovarian Carcinoma.
AB  - ATIC, SHMT2, and SLC46A1 have essential roles in one-carbon (1-C) transfer. The
      authors examined whether associations between ovarian carcinoma and 15 variants
      in these genes are modified by regular multivitamin use, a source of 1-C donors,
      among Caucasian participants from two US case-control studies. Using a phased
      study design, variant-by-multivitamin interactions were tested, and associations
      between variants and ovarian carcinoma were reported stratified by multivitamin
      supplement use. Per-allele risk associations were modified by multivitamin use at
      six variants among 655 cases and 920 controls (Phase 1). In a larger sample of
      968 cases and 1,265 controls (Phases 1 and 2), interactions were significant (P
      <= 0.03) for two variants, particularly among regular multivitamin users: ATIC
      rs7586969 [odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.6-0.9] and
      ATIC rs16853834 (OR = 1.5, 95% CI = 1.1-2.0). The two ATIC single nucleotide
      polymorphisms (SNPs) did not share the same haplotype; however, the haplotypes
      they comprised mirrored their SNP risk associations among regular multivitamin
      supplement users. A multi-variant analysis was also performed by comparing the
      observed likelihood ratio test statistic from adjusted models with and without
      the two ATIC variant-by-multivitamin interaction terms with a null distribution
      of test statistics generated by permuting case status 10,000 times. The
      corresponding observed P value of 0.001 was more extreme than the permutation
      derived P value of 0.009, suggesting rejection of the null hypothesis of no
      association. In summary, there is little statistical evidence that the 15
      variants are independently associated with risk of ovarian carcinoma. However,
      the statistical interaction of ATIC variants with regular multivitamin intake,
      when evaluated at both the SNP and gene level, may support these findings as
      relevant to ovarian health and disease processes.

PMID- 22461785
TI  - A Scheduling Algorithm for Computational Grids that Minimizes Centralized
      Processing in Genome Assembly of Next-Generation Sequencing Data.
AB  - Improvements in genome sequencing techniques have resulted in generation of huge
      volumes of data. As a consequence of this progress, the genome assembly stage
      demands even more computational power, since the incoming sequence files contain
      large amounts of data. To speed up the process, it is often necessary to
      distribute the workload among a group of machines. However, this requires
      hardware and software solutions specially configured for this purpose. Grid
      computing try to simplify this process of aggregate resources, but do not always
      offer the best performance possible due to heterogeneity and decentralized
      management of its resources. Thus, it is necessary to develop software that takes
      into account these peculiarities. In order to achieve this purpose, we developed
      an algorithm aimed to optimize the functionality of de novo assembly software
      ABySS in order to optimize its operation in grids. We run ABySS with and without
      the algorithm we developed in the grid simulator SimGrid. Tests showed that our
      algorithm is viable, flexible, and scalable even on a heterogeneous environment,
      which improved the genome assembly time in computational grids without changing
      its quality.

PMID- 22461786
TI  - Extending local canonical correlation analysis to handle general linear contrasts
      for FMRI data.
AB  - Local canonical correlation analysis (CCA) is a multivariate method that has been
      proposed to more accurately determine activation patterns in fMRI data. In its
      conventional formulation, CCA has several drawbacks that limit its usefulness in
      fMRI. A major drawback is that, unlike the general linear model (GLM), a test of
      general linear contrasts of the temporal regressors has not been incorporated
      into the CCA formalism. To overcome this drawback, a novel directional test
      statistic was derived using the equivalence of multivariate multiple regression
      (MVMR) and CCA. This extension will allow CCA to be used for inference of general
      linear contrasts in more complicated fMRI designs without reparameterization of
      the design matrix and without reestimating the CCA solutions for each particular
      contrast of interest. With the proper constraints on the spatial coefficients of
      CCA, this test statistic can yield a more powerful test on the inference of
      evoked brain regional activations from noisy fMRI data than the conventional t
      test in the GLM. The quantitative results from simulated and pseudoreal data and
      activation maps from fMRI data were used to demonstrate the advantage of this
      novel test statistic.

PMID- 22461788
TI  - Visualization of laterally spreading colorectal tumors by using image-enhanced
      endoscopy.
AB  - Laterally spreading tumors may sometimes evade detection by colonoscopy. This
      study aimed to evaluate the use of image-enhanced endoscopy for visualizing
      laterally spreading tumors of the nongranular type. We reviewed consecutive
      patients with 47 non-granular-type laterally spreading tumors that had been
      examined using white-light imaging, autofluorescence imaging, narrow-band
      imaging, and chromoendoscopy with indigo carmine. The quality of visualization
      was evaluated using a 5-point scale by less- and more-experienced endoscopists.
      Autofluorescence imaging provided significantly better visualization than white
      light imaging for both less-experienced and experienced endoscopists. On the
      other hand, no significant differences were observed between the quality of
      visualization provided by white-light imaging and narrow-band imaging for less
      experienced endoscopists. Autofluorescence imaging provides high-quality
      visualization of non-granular-type laterally spreading tumors on still images.
      Multicenter trials should be conducted to confirm the usefulness of
      autofluorescence imaging in detecting laterally spreading colorectal tumors.

PMID- 22461787
TI  - New experimental models of diabetic nephropathy in mice models of type 2
      diabetes: efforts to replicate human nephropathy.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The
      use of experimental models of DN has provided valuable information regarding many
      aspects of DN, including pathophysiology, progression, implicated genes, and new
      therapeutic strategies. A large number of mouse models of diabetes have been
      identified and their kidney disease was characterized to various degrees. Most
      experimental models of type 2 DN are helpful in studying early stages of DN, but
      these models have not been able to reproduce the characteristic features of more
      advanced DN in humans such as nodules in the glomerular tuft or
      glomerulosclerosis. The generation of new experimental models of DN created by
      crossing, knockdown, or knockin of genes continues to provide improved tools for
      studying DN. These models provide an opportunity to search for new mechanisms
      involving the development of DN, but their shortcomings should be recognized as
      well. Moreover, it is important to recognize that the genetic background has a
      substantial effect on the susceptibility to diabetes and kidney disease
      development in the various models of diabetes.

PMID- 22461789
TI  - Perisynaptic GABA Receptors The Overzealous Protector.
AB  - An attempt to find pharmacological therapies to treat stroke patients and
      minimize the extent of cell death has seen the failure of dozens of clinical
      trials. As a result, stroke/cerebral ischemia is the leading cause of lasting
      adult disability. Stroke-induced cell death occurs due to an excess release of
      glutamate. As a consequence to this, a compensatory increased release of GABA
      occurs that results in the subsequent internalization of synaptic GABA(A)
      receptors and spillover onto perisynaptic GABA(A) receptors, resulting in
      increased tonic inhibition. Recent studies show that the brain can engage in a
      limited process of neural repair after stroke. Changes in cortical sensory and
      motor maps and alterations in axonal structure are dependent on patterned
      neuronal activity. It has been assumed that changes in neuronal excitability
      underlie processes of neural repair and remapping of cortical sensory and motor
      representations. Indeed, recent evidence suggests that local inhibitory and
      excitatory currents are altered after stroke and modulation of these networks to
      enhance excitability during the repair phase can facilitate functional recovery
      after stroke. More specifically, dampening tonic GABA inhibition can afford an
      early and robust improvement in functional recovery after stroke.

PMID- 22461790
TI  - Redefining hormone sensitive disease in advanced prostate cancer.
AB  - Prostate cancer is the most common cancer among men in the United States. For
      decades, the cornerstone of medical treatment for advanced prostate cancer has
      been hormonal therapy, intended to lower testosterone levels, known as Androgen
      Deprivation Therapy (ADT). The development of hormone-resistant prostate cancer
      (now termed castration-resistant prostate cancer:CRPC) remains the key roadblock
      in successful long-term management of prostate cancer. New advancements in
      medical therapy for prostate cancer have added to the hormonal therapy
      armamentarium. These new therapeutic agents not only provide a survival benefit
      but also show potential for reversing hormonal resistance in metastatic CRPC, and
      thus redefining hormonally sensitive disease.

PMID- 22461791
TI  - HDR Brachytherapy in the Management of High-Risk Prostate Cancer.
AB  - High-dose-rate (HDR) brachytherapy is used with increasing frequency for the
      treatment of prostate cancer. It is a technique which allows delivery of large
      individual fractions to the prostate without exposing adjacent normal tissues to
      unacceptable toxicity. This approach is particularly favourable in prostate
      cancer where tumours are highly sensitive to dose escalation and to increases in
      radiotherapy fraction size, due to the unique radiobiological behaviour of
      prostate cancers in contrast with other malignancies. In this paper we discuss
      the rationale and the increasing body of clinical evidence for the use of this
      technique in patients with high-risk prostate cancer, where it is combined with
      external beam radiotherapy. We highlight practical aspects of delivering
      treatment and discuss toxicity and limitations, with particular reference to
      current practice in the United Kingdom.

PMID- 22461793
TI  - Effect of domperidone on insufficient lactation in puerperal women: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - Background. There is a controversy within the medical community regarding the
      role of domperidone as a galactagogue and the drug has been removed from the US
      market owing to safety concerns. Objective. To perform a systematic review and
      meta-analysis of the available data assessing the effect of domperidone on breast
      milk production in women experiencing insufficient lactation. Study Selection.
      Randomized controlled trials (RCTs) examining the effect of domperidone on breast
      milk production of puerperal women were eligible for inclusion. Data Analysis.
      Absolute and relative changes from baseline were calculated for individual
      studies and pooled using a random effects model. Results. Three RCTs including 78
      participants met the inclusion criteria. All showed a statistically significant
      increase in breast milk production following treatment with domperidone. The
      analysis of pooled data demonstrated a statistically significant relative
      increase of 74.72% (95%  CI = 54.57; 94.86, P < 0.00001) in daily milk production
      with domperidone treatment compared to placebo. No maternal or neonatal adverse
      events were observed in any of the trials. Conclusions. Evidence from a few small
      RCTs of moderate to high quality suggests that domperidone produces a greater
      increase in breast milk supply than placebo.

PMID- 22461795
TI  - From the Editor-in-Chief.

PMID- 22461794
TI  - A rare cause of the cough: primary small cell carcinoma of esophagus-case report.
AB  - Primary small cell carcinoma of the esophagus is a relatively rare malignancy. It
      is highly progressive and poorly prognostic in untreated conditions. In the
      western populations, the rate of primary small cell carcinoma in all esophageal
      cancer types is between 0.05% and 2.4%, while it is endemically increasing up to
      7.6% in the eastern populations. Most of the cases are in extensive stage at the
      time of diagnosis. Surgery is the treatment of choice in limited stages, but
      treatment must be multimodal in primary small cell carcinoma of the esophagus. A
      47-year-old woman was referred to our clinic with gradually increasing severe dry
      cough and slight difficulty in swallowing for 20 days. Chest X-ray graphy was
      normal, and computed tomography of the chest showed multiple mediastinal lymph
      nodes and hepatic metastases. Her endoscopic examination revealed an endoluminal
      vegetative mass between 20 cm and 23 cm of her esophagus. The case was reported
      as small cell carcinoma of the esophagus on histopathological examination. The
      case was assumed inoperable, and chemotherapy and radiotherapy were planned. We
      presented a rare cause of the cough and primary esophageal small cell carcinoma
      in this paper.

PMID- 22461792
TI  - The use of mouse models for understanding the biology of down syndrome and aging.
AB  - Down syndrome is a complex condition caused by trisomy of human chromosome 21.
      The biology of aging may be different in individuals with Down syndrome; this is
      not well understood in any organism. Because of its complexity, many aspects of
      Down syndrome must be studied either in humans or in animal models. Studies in
      humans are essential but are limited for ethical and practical reasons.
      Fortunately, genetically altered mice can serve as extremely useful models of
      Down syndrome, and progress in their production and analysis has been remarkable.
      Here, we describe various mouse models that have been used to study Down
      syndrome. We focus on segmental trisomies of mouse chromosome regions syntenic to
      human chromosome 21, mice in which individual genes have been introduced, or mice
      in which genes have been silenced by targeted mutagenesis. We selected a limited
      number of genes for which considerable evidence links them to aspects of Down
      syndrome, and about which much is known regarding their function. We focused on
      genes important for brain and cognitive function, and for the altered cancer
      spectrum seen in individuals with Down syndrome. We conclude with observations on
      the usefulness of mouse models and speculation on future directions.

PMID- 22461796
TI  - Fracture unit: a (possible) model of implementation in Italy.
AB  - The "Fracture Unit" is one of the possible answers to the advanced health needs
      of the growing number of elderly in our Country, aimed at achieving effective and
      efficient management of fracture events due to osteoporosis or fragility
      fractures. Here we proposed an implementation model that can represent an ideal
      and virtuous path that should be dedicated to every fractured patient. This model
      should provide specific responses to the health needs of the fractured patient
      and specifically responses to the health needs of the subject as a frail patient.
      The goal of this model is therefore to define and structure "a priori" a
      multidisciplinary course where the patient should be automatically inserted at
      the time of contact with the health facility following the fracture event, to
      establish a similar structured course even for the post-acute phase, that is
      taken over by large social-health areas or districts; and meet the cost for the
      definition of the rehabilitation.An optimal communication between hospital and
      general practitioners, responsible necessarily of the continuous reassessment of
      the patient, and the monitoring of patient's adherence to treatment are needed
      for a successful outcome and application of the implementation's model.

PMID- 22461797
TI  - Radiological diagnostic progress in skeletal diseases.
AB  - High-resolution bone imaging has made tremendous progress in the recent past.
      Both imaging modalities, computed tomography as well as MR imaging, have improved
      image quality. New developments such as HR-pQCT now make it possible to acquire
      in vivo images at peripheral sites with isotropic voxel size in a very short
      time. Further enhancements in the MR field have made it possible to image more
      central body sites such as the proximal femur with very high spatial resolution.
      New analysis methods can obtain direct estimates of biomechanical properties and
      important information related to bone's topology, as well as parameters of scale
      and orientation. These accomplishments will be essential in the noninvasive
      assessment of osteoporosis and fracture risk, will provide insight into the
      mechanisms behind bone loss, and will increasingly play a role as a tool for
      assessing treatment efficacy.

PMID- 22461798
TI  - Bone healing: little secrets.
AB  - The development of new strategies to enhance the healing of fractures continues
      to evolve with the introduction of both locally and systemically delivered
      compounds. The recent refinement in the use of autologous bone marrow as a bone
      graft material has brought the field of stem cell biology into orthopaedic
      practice. New recombinant peptides such as platelet- derived growth factor and
      teriparatide show promise as local and systemic enhancers respectively. Finally,
      recent evidence that mutations in elements of the Wnt signalling pathway lead to
      gain-of-function mutations in bone formation in rare clinical settings has
      provided the basis for the targeting of this pathway for the development of
      therapeutic agents for bone repair. These recent developments are presented as
      the "little secrets" of present day bone healing.

PMID- 22461799
TI  - New biomaterials for bone regeneration.
AB  - Bone-grafting techniques either with autografts or allografts still represent a
      challenge for reconstructive surgery.Allografts and autografts are the current
      strategies for filling bone defects and subsequent repair but each have
      drawbacks. Synthetic bone-graft substitutes, developed in an effort to overcome
      the inherent limitations of autograft and allograft, represent an alternative
      strategy. Synthetic bone graft substitutes have the goal of mimicking the
      physical and mechanical nature of native tissue and to promote osteoconduction
      for bone regeneration. In addition these substitutes are capable to release drugs
      or growth factors in a temporally and spatially manner. Some biomaterials are
      employed to design biomimetic scaffold such as natural and synthetic polymers,
      ceramics, metallics and composites.The purpose of this paper is to provide an
      overview of the main biomaterials used for bone reconstruction.

PMID- 22461800
TI  - The use of autologous blood-derived growth factors in bone regeneration.
AB  - Platelet-rich plasma (PRP) is defined as a portion of the plasma fraction of
      autologous blood having platelet concentrations above baseline. When activated
      the platelets release growth factors that play an essential role in bone healing
      such as Platelet-derived Growth Factor, Transforming Growth Factor-beta, Vascular
      Endothelial Growth Factor and others.Multiple basic science and in vivo animal
      studies agree that PRP has a role in the stimulation of the healing cascade in
      ligament, tendon, muscle cartilage and in bone regeneration in the last years PRP
      had a widespread diffusion in the treatment of soft tissue and bone healing.The
      purpose of this review is to describe the biological properties of platelets and
      its factors, the methods used for producing PRP, to provide a background on the
      underlying basic science and an overview of evidence based medicine on clinical
      application of PRP in bone healing.

PMID- 22461801
TI  - Bone disease in HIV infection.
AB  - The advent of highly active anti-retroviral therapy (HAART) has dramatically
      decreased the rate of AIDS-related mortality and significantly extended the life
      span of patients with AIDS.A variety of metabolic side effects are associated
      with these therapies, one of which is metabolic bone disease. The causes of low
      bone mineral density (BMD) in individuals with HIV infection appear to be
      multifactorial and likely represent a complex interaction between HIV infection,
      traditional osteoporosis risk factors, and antiretroviral related factors.This
      review summarizes the clinical evidence linking HIVassociated osteoporosis to
      direct infection and antiretroviral therapy use. The purported mechanisms
      involved in bone loss are also reviewed. Additionally, recommendations regarding
      the pharmacologic management of HIV/HAART-related osteoporosis are given. In
      conclusion, we make the point that HIV infection should be considered as a risk
      factor for bone disease.

PMID- 22461803
TI  - Osteosynthetic improvement of osteoporotic bone: prevention surgery.
AB  - A prior osteoporotic femoral neck fracture (FNF) doubles the risk of a second,
      contralateral hip fracture. Pharmacological prevention of osteoporotic fractures
      is cost-effective but medication compliance and persistence rates are
      suboptimal.The aim of our study was to evaluate the safety and effectiveness of a
      device developed for the surgical prevention of an additional contralateral FNF
      in elderly osteoporotic patients.Only patients with a T score <= -2.5 were
      enrolled and randomized either to receive (Group A) or not receive (Group B)
      surgical prevention. Sixty-seven patients were enrolled. The mean follow-up was
      16 months (range 1 to 22). To date, no contralateral FNF has been reported in
      either group. In Group A, no device-related complications were recorded. Twelve
      patients reported one or more falls and in four cases a non-femoral fragility
      fracture occurred.The main problem with pharmacological prevention is therapy
      adherence and the extensive period needed for only a slight improvement in bone
      strength.Surgical prevention is a potential solution for avoiding the occurrence
      of a second contralateral FNF. Nevertheless, a longer follow-up and a larger
      cohort of patients is necessary in order to verify the true effectiveness of the
      surgical prevention in elderly osteoporotic patients.

PMID- 22461804
TI  - Ibandronate and periprosthetic bone mass: new therapeutic approach in
      periprosthetic loosening prevention.
AB  - A prosthetic implant modifies the physiological transmission of loads to the
      bone, initiating a remodeling process.Studies of the mechanisms responsible for
      periprosthetic bone loss contributed to the definition of new pharmacological
      strategies that may prevent aseptic implant loosening. Bisphosphonates are a
      class of drugs useful to this purpose, and have been shown to be effective in
      reducing periprosthetic resorption during the first year after the implant. We
      aimed to assess the inhibitory effect on periprosthetic osteolysis of
      ibandronate, a highly potent aminobisphosphonate, administered orally and IV with
      an extended interval between doses and optimal treatment adherence. In view of
      the fact that periprosthetic remodeling takes place during the first 6-12 months
      after surgery and is ultimately responsible for prosthesis longevity, we may
      conclude that the administration of high dosage ibandronate postsurgery by IV
      bolus and subsequently as cyclic oral treatment reduced cortical osteopenia in
      the metaphyseal region, and in the calcar region of the proximal femur. This
      therapy might therefore be used as preventive measure against postsurgical
      osteopenia and probably also against aseptic loosening.

PMID- 22461805
TI  - Analysis of the costs and consequences of adherence to therapy in hip fracture
      patients. Results of a longitudinal analysis of.
AB  - The aim of this study, a retrospective cohort analysis, was to calculate the
      costs and consequences of exposure to and compliance with drug treatments
      recommended for refracture prevention in post-menopausal women with hip fracture.
      All women aged >=65 years and admitted to hospital with a main or secondary
      diagnosis of hip fracture in the period 1 January 2006 - 31 December 2008 were
      included. These patients were classified as exposed /not exposed to a drug
      treatment for fracture prevention. Adherence to treatment was calculated in the
      group of patients treated with bisphosphonates. The following items were
      considered in the cost analysis: drug treatments supplied, diagnostic tests
      administered and hospital admissions recorded during the observation period. In
      total, 5,167 patients were included in the analysis, of whom only 33.9% received
      drug therapy post hip fracture; of those treated with bisphosphonates, only 21.1%
      were found to have adhered to the treatment. Exposure to drug treatment reduced
      the risk of refracture by 39.5% and the risk of death by 55.1%. The mean cost
      increases observed in the patients who, according to indication, were exposed to
      drug treatment (+ ? 256) or submitted to a diagnostic test (+ ? 40) were offset
      by a sizeable reduction in costs of hospitalisation for refracture (- ? 703).Drug
      treatment for the prevention of bone refractures in hip fracture patients was
      found to be effective in reducing the risk of refracture and death, and cost
      effective, reducing overall patient management costs.

PMID- 22461802
TI  - Construction of a database for the evaluation and the clinical management of
      patients with breast cancer treated with antiestrogens and/or aromatase
      inhibitors.
AB  - Breast cancer, mostly exhibiting an hormone-dependent pathogenesis, is a commonly
      diagnosed cancer in females.It is well known that sex steroids favor the process
      of carcinogenesis of breast tissue and anti-hormonal therapy of breast cancer
      aims to decrease the action of estrogens on this tissue. For this purpose, two
      different compounds are prevalently used: the Selective Estrogen Receptor
      Modulators, preventing the cancer cell to interact with estrogens, and Aromatase
      Inhibitors, inhibiting the tissue conversion of androgens into estrogens.
      Unfortunately, latter treatments negatively impact on bone mass leading to the
      onset of osteoporosis. For this purpose, we propose to build a database to
      afford, to store and analyze information about the effects of treatment with
      Selective Estrogen Receptor Modulators and/or Aromatase Inhibitors on bone
      metabolism in patients with breast cancer referred to Our Center. We will focus
      on the possibility of intervening to reduce the negative effects on bone both by
      the identification of modifiable risk factors and administration of specific
      therapies, in order to create a therapeutic, diagnostic standard workup for these
      diseases.

PMID- 22461807
TI  - From the Editor-in-Chief.

PMID- 22461806
TI  - The bone care nurse project.
AB  - In today's society, citizens are called to play an increasingly active role in
      decision planning related to the various aspects of work, social and political
      life. This trend has been also confirmed in the health's field. In fact, the
      citizen is also required to have the skills to take responsibility for his/her
      own health, to have knowledge of the health care system, understand the advice
      and instructions of health professionals, actively participating with them in the
      therapeutical path. The lack or an inadequate level of these skills will affect
      both the health of the individual and the costs related to the National Health
      System. The nursing staff that interfaces between physicians and patients plays a
      key role in health's promotion as an important determinant of health and welfare
      of the patient-citizen. With regard to osteoporosis, due to better knowledge of
      its determining causes, it is now possible an easy access to diagnosis and
      treatment options before fragility fractures occur, providing a real prevention
      to such complications. Prevention must be addressed to two different, but
      related, objectives: 1) prevention of osteoporosis; and 2) prevention of
      fragility fractures in patients with osteoporosis. In the context of both primary
      and secondary prevention, the nurse can better informed the patients and/or
      citizens about either the risks related to an inappropriate behavior or
      situations and events particularly dangerous to health, as well as provide
      information to simply and effectively implement protective measures. This project
      aims to raise awareness and create competent and specialized nurse figures, with
      a good understanding of the bone diseases, through the organization of seminars
      and training courses. Thus, it will be create clinical pathways and welfare in
      which the figure of the "Bone Care Nurse" will be responsible for administration
      of questionnaires relating to lifestyle and, for patients in drug treatment,
      questionnaires designed to assess the relevance of the adherence/compliance to
      the prescribed therapy. The "Bone Care Nurse" will also provide specific
      information leaflets aimed at improving lifestyle, compliance and adherence to
      therapy prescribed by physician. Specifically, this program will cover not only
      the prevention of fragility fractures in patients with low bone mass but also
      will provide general information on healthy lifestyles, such as adequate diet and
      physical activity, helpful to prevent cardiovascular disease, diabetes, obesity.
      An increase patient's compliance in taking the antiosteoporotic therapy, as also
      other concomitant medications will be obtainable. The information collected will
      be stored in an electronic database, subject to statistical analysis and will be
      informative on both the degree of knowledge of disease by the patient at the
      first and follow-up meetings of the Bone Care Nurse project.

PMID- 22461808
TI  - Skeletal fragility definition.
AB  - Strategies to reduce fracture risk must be based on the understanding of the
      mechanisms that underline the increased incidence of fractures with age and with
      bone diseases that reduce bone stock. There is evidence that in addition to bone
      minerals density, other factors influence bone strength. This study reviews the
      biomechanical aspects of age-related fractures, including the interacting roles
      of traumatic loading and bone strength, and the factors that determine the
      resistances of bones to fracture. Although low bone mineral density (BMD) is
      among the strongest risk factors for fracture, a number of clinical studies have
      demonstrated the limitations of bone mineral density measurements in assessing
      fracture risk and monitoring the response to therapy. These observations have
      brought renewed attention to the broader array of factors that influence skeletal
      fragility, including bone size, shape, micro-architecture and bone quality. Bone
      fragility can be defined by biomechanical parameters, including ultimate force,
      ultimate displacement and energy absorption. Many osteoporosis treatments build
      bone mass but also change tissue quality. Antiresorptive therapies, such as
      bisphosphonates, substantially reduce bone turnover, impairing micro-damage
      repair and causing increased bone mineralization, which can increase the
      brittleness of bone. Anabolic therapies, such as teriparatide, increase bone
      turnover and porosity, which offset some of the positive effects on bone
      strength. Osteoporosis therapies may also affect bone architecture by causing the
      redistribution of bone structure. Restructuring of bone during treatment may
      change bone fragility, even in the absence of drug effects on BMD.

PMID- 22461809
TI  - Hip painful prosthesis: surgical view.
AB  - Painful hip prosthesis is the most feared immediate and remote complication of a
      primary implant and usually represents the failure of one or more therapeutic
      moments. In cases of aseptic implant failure, the causes invoked may be
      represented by an incorrect indication, the quality of materials, local and
      general condition of the patient and especially from a bad joint biomechanics. In
      cases of septic loosening, however, the cause of failure to be found in the
      location of pathogens within the implant. In planning a revision is necessary to
      respect many important steps. They are represented by the exact identification of
      the causes of failure, the correct preoperative planning, by respecting the skin
      incisions, the proper choice of the prosthesis, planning the surgical technique,
      and finally by an appropriate rehabilitation program.In the evaluation of hip
      failure the first diagnostic step is to recognize exactly those aseptic and
      septic forms anyway to exclude the diagnosis of infection.

PMID- 22461810
TI  - Painful hip arthroplasty: definition.
AB  - Total hip arthroplasty (THA) has been indicated as the surgical intervention with
      greatest improvement in pain and physical function. However some patients
      continue to experience hip pain after elective surgery. We investigate prognostic
      factors that negatively affect treatment effectiveness and the patient outcome.
      The "hip region" constitutes the groin, buttock, upper lateral thigh, greater
      trochanteric area, and the iliac crest. Pain originating from various sources and
      not directly linked to prosthesis may be perceived here and includes the
      lumbosacral spine, referred pain from abdominal organs and soft tissue sources
      such as trochanteric bursitis, tendinitis, hip abductor dysfunction, and inguinal
      hernia. An accurate assessment of the pain cause is extremely difficult to
      construct and a complete differential diagnosis is fundamental. We assess all the
      possible causes of hip pain after THA and we divide them depending on the
      presence or absence of radiographic signs.

PMID- 22461811
TI  - Painful knee arthroplasty: definition and overview.
AB  - Total Knee Arthroplasty (TKA) is one of the most successful procedures in
      Orthopaedic Surgery, with good clinical results and high survival rate in more
      than 90% of the cases at long-term follow-up. Since the increase of population's
      mean age, worsening of articular degenerative alterations, and articular sequelae
      related to previous fractures, there is a persistent growing of the number of
      knee arthroplasties in every country each year, with expected increase of
      complications rates. Painful TKA is considered an unusual complication, but
      several reports focus on this challenging clinical issue.Common causes of painful
      TKA may be divided as early or late, and in referred, periarticular or intra
      articular. Among the early, we recall implant instability (related to surgical
      and technical mistakes) and problems of extensor mechanism (patella not
      resurfaced, malalignment of femoral, tibial, or patellar component, tendons
      failure or degeneration). Late causes of painful TKA are almost related to
      aseptic loosening and infection, but also, even if unusual, reflex sympathetic
      dystrophy, synovitis, and hypersensitivity to metal implants are
      represented.Hypersensitivity to metal is a clinical issue with significative
      increase, but to date without a specific characterization. The Authors report
      about incidence, clinical features, and diagnostic pathways of hypersensitivity
      to metal implants, focusing on the prevention of this challenging problem.

PMID- 22461812
TI  - Painful knee prosthesis: surgical approach.
AB  - There are many conditions that may be responsible of a painful knee prosthesis.
      The possible causes are not always easily diagnosed. Common causes of prosthetic
      failure, such as aseptic loosening, infection, instability, progressive patellar
      arthropathy and recurrent synovitis are associated with clearly defined
      radiographic and/or clinical evidence. Prosthetic infection should always be
      considered first until any other cause has been demonstrated. In the presence of
      an infected prosthesis we carry out a two-step revision. Aseptic loosening needs
      implant revision more often with increasing prosthesis stability. Varus-valgus,
      anteroposterior, global and patello-femoral instability are failures often due to
      technical errors; superstabilized or constrained implants are needed depending on
      the instability entity.In presence of patello-femoral pain it is necessary to
      evaluate the stability of the patellar component and any alterations in its
      motion. Patellar progressive arthropathy can often cause late-onset knee pain; in
      this case patella resurfacing is needed. Altered patellar tracking, may need a
      lateral release but in some cases is related to misalignment of the components
      and the revision procedure is mandatory. Nevertheless, the diagnosis and
      treatment of a painful knee prosthesis can be extremely difficult if there is no
      clear evidence of any of the most common causes of failure. Referred pain,
      ligament and tendon dysfunction, cutaneous neuromas, synovitis, a patellar clunk
      have to be diagnosed and treated.A possible aetiological understimated factor is
      painful knee prosthesis due to metals sensibilization, in particular to nickel.
      In this event the quantity of nickel in the revision prosthesis must be minimal.

PMID- 22461813
TI  - Epidemiology of fragility fractures in Italy.
AB  - OBJECTIVES: We aimed to calculate the incidence of major fragility fractures in
      Italy, including those which do not result systematically in hospital admissions,
      on the basis of hospitalization rates provided in our previous researches.
      METHODS: We analyzed Italian national hospital discharge data from year 2004 to
      2006 in order to determine age- and sex-specific incidence rates of hip,
      vertebral, humeral, and forearm fractures occurred in people aged 40 to 100 years
      of age. Re-hospitalizations of the same patients have been excluded from the
      analysis. Hospital discharge data have been adjusted taking into account recently
      published information concerning fracture-specific hospitalization rates.
      RESULTS: We estimated a total of 88,647 hip fractures in year 2006 among people
      aged 40 to 100 years old, with a +5.9% increase across the three examined years.
      Women aged >75 years old (n=53,259) accounted for 60% of total fractures observed
      both in males and females from 40 to 100 years of age. Concerning males, the
      highest incidence was observed between 80 and 84 years old (about 5,000 hip
      fractures). Overall incidence rate per 100,000 inhabitants computed for hip
      fractures was 284.28, with marked age- and sex-specific differences. Clinical
      vertebral fractures were estimated to be almost 61,000 in 2006, with a +3.1%
      increase across the three examined years. Overall incidence rate per 100,000
      inhabitants computed for clinical vertebral fractures was 195.23, but this value
      doubled between 75 and 95 years of age. In the same year 2006, a total of 56,129
      humeral and 97038 forearm/wrist fractures, with a +5.5% and +3.9% increase across
      three years, respectively. Overall humeral fractures incidence per 100,000 was
      180, with highest rates (up to 600 and over) observed in women between 75 and 95
      years of age, while incidence per 100,000 computed for wrist fractures was 311,
      with top values observed in women between aged 55-85 years old - thus including
      early post-menopausal age group - and a peak in those between 75 and 79 years of
      age. CONCLUSIONS: The burden of major osteoporotic fractures in Italy is very
      high. Preventive strategies aimed to reduce fractures incidence should be carried
      out at regional level.

PMID- 22461814
TI  - Femoral fractures in the extremely elderly.
AB  - At the Trauma Unit of Pisa we performed an observational study reviewing nineties
      that about 200 patients were treated and underwent surgery for femoral neck
      fracture from 1998 to 2005. The clinical and radiographic results obtained were
      discrete, with a mortality of 42.5%, the survivors are still having a good
      quality of life.

PMID- 22461815
TI  - Domino Effect: mechanic factors role.
AB  - The rapid onset of the Domino Effect following the first Vertebral Compression
      Fracture is a direct consequence of the mechanical variations that affect the
      spine when physiological curves are modified. The degree of kyphosis influences
      the intensity of the Flexor Moment; this is greater on vertebrae D7, D8 and on
      vertebrae D12, L1 when the spine flexes. Fractures of D7, D8, D12 and L1 are, by
      far, the most frequent and also the main cause of the mechanical alterations that
      can trigger the Domino Effect. For these considerations vertebrae D7, D8, D12 and
      L1 have to be taken in consideration as "critical". In the case of critical
      clinical vertebral fractures it is useful to provide an indication for minimally
      invasive surgical reduction or intrasomatic stabilization. When occurs a fracture
      of a "critical vertebra", prompt restoration of the heights leads to a reduction
      in the Kyphosis Index and therefore in the Flexor Moment, not only of the
      fractured vertebra but also, in turn, of all the other metameres which, even if
      morphologically still intact, are structurally fragile; so, through the
      restoration of the mechanical vertebral proprieties, we can reduce the risk of
      the Domino Effect. At the same time the prompt implementation of osteoinductive
      therapy is indispensable in order to achieve rapid and intense reconstruction of
      the trabecular bone, the strength of which increases significantly in a short
      period of time. Clinical studies are necessary to confirm the reduction of the
      domino effect following a fragility fracture of "critical vertebrae" with the
      restoration of the mechanical properties together with anabolic therapy.

PMID- 22461816
TI  - "Toxic" beef bone soup.
AB  - Hypercalcaemia is most commonly caused by primary hyperparathyroidism or
      malignancy. Vitamin D intoxication, also a cause of hypercalcaemia, is mostly
      caused by excessive administration of vitamin D-containing medications and
      excessive intake of foods fortified with vitamin D. We present a young cricketer,
      with recurrent vomiting due to hypercalcaemia and hypervitaminosis D, who used to
      drink large volumes of soup prepared by boiling long beef bones, for many months.
      This case presentation highlights the importance of in-depth dietary history for
      arriving at proper diagnosis.

PMID- 22461817
TI  - Oncogenic osteomalacia due to phosphaturic mesenchymal tumor of the craniofacial
      sinuses.
AB  - BACKGROUND: The phosphaturic mesenchymal tumor of the craniofacial sinuses (mixed
      connective tissue variant) is an extremely rare, distinctive paraneoplastic
      syndrome that is frequently associated with oncogenic osteomalacia. METHODS: In
      this report is presented a case of 22 years old man indicated four years of
      progressive generalized pain and weakness, eventually becoming wheel-chair bound.
      His current presentation was for chest pain resulting from atraumatic rib
      fractures. RESULTS: Imaging showed osteoporosis and multiple insufficiency
      fractures. CT and MRI showed an ethmoid mass. He had no symptoms referable to his
      nose or sinuses. CONCLUSIONS: The ethmoid lesion was completely excised, the
      patient's laboratory parameters returned to normal levels and the patient's
      symptoms disappeared.

PMID- 22461818
TI  - Ebstein's anomaly in a child with osteogenesis imperfecta type I.
AB  - Cardiovascular involvement is relatively rare in osteogenesis imperfecta and has
      a predilection for left-sided cardiac valves. We report a 5 years old female
      child affected by osteogenesis imperfecta type I in which an asymptomatic mild
      form of Ebstein's anomaly, a congenital tricuspid malformation, was diagnosed
      during routinely investigation. The association of these two relatively rare
      entities could provide new insight to better understand the pathogenesis of
      cardiac involvement in osteogenesis imperfecta.

PMID- 22461819
TI  - Was true gout? New interpretations of the skeletal disease(s) of the Medici
      family.

PMID- 22461820
TI  - From the Editor-in-Chief.

PMID- 22461821
TI  - Phosphatonins: new hormones involved in numerous inherited bone disorders.
AB  - Phosphate (Pi) homeostasis is under control of several endocrine factors that
      play effects on bone, kidney and intestine. The control of Pi homeostasis has a
      significant biological importance, as it relates to numerous cellular mechanisms
      involved in energy metabolism, cell signaling, nucleic acid synthesis, membrane
      function, as well as skeletal health and integrity. Pi is essential for diverse
      biological processes, and negative Pi balance resulting from improperly regulated
      intestinal absorption, systemic utilization, and renal excretion. As results of
      these functions, chronic Pi deprivation causes several biological alterations,
      such as bone demineralization with unmineralized osateoid typical of osteomalacia
      in adults and rickets in developing animals and humans (1). Phosphatonins are new
      hormones playing an important role in the control of Pi homeostasis together with
      parathyroid hormone (PTH) and 1,25-dihydroxy vitamin D(3). Most insight into the
      underlying mechanisms was established by defining the molecular basis of
      different inherited disorders that are characterized by an abnormal regulation of
      Pi homeostasis.

PMID- 22461822
TI  - Osteomalacia can still be a point of attention to celiac disease.
AB  - Celiac disease (CD), a malabsorption syndrome with a genetic base, is a
      consequence of hypersensitivity to GLUTEN-containing foods. CD can manifest with
      classic symptoms; however, some unusual features like osteomalacia that has
      become more and more rare, may be the presenting symptom. We describe here a case
      of osteomalacia secondary to delayed diagnosis of celiac disease. This patient
      complained about progressive limping, weakness, short stature, and skeletal
      deformities. Radiological and laboratory findings were all in favor of
      osteomalacia. Celiac disease was mentioned according to the history of subtle
      intermittent diarrhea, abdominal discomfort and confirmed with intestinal biopsy
      and detection of specific autoantibodies. Improvement of patient's weakness and
      laboratory abnormalities was obvious after treatment with gluten free diet,
      vitamin D, calcium and other trace elements. In conclusion, this case affirms
      that chronic celiac disease especially untreated one, can lead to irreversible
      complications like skeletal deformities and short stature.

PMID- 22461823
TI  - Osteoporosis and Parkinson's disease.
AB  - Parkinson's disease (PD) and osteoporosis are two conditions with a quite high
      prevalence in older people. From the literature we learn that in parkinsonian
      people there a is e major reduction of Bone Mass Density (BMD) compared to age
      matched controls. A low BMD is one of the factors related to fracture's frequency
      in PD patients besides an increased risk of falls. From the standpoint
      pathophysiology, various factors are involved in osteoporosis: immobilization,
      endocrine factors like hypovitaminosis D, nutritional and iatrogenic
      factors.Considering morbidity and mortality related to fractures in old people
      and in particular in PD patients it is reasonable that these patients would
      undergo to vitamin and BMD measuring, to fall risk assessment and that all
      preventive measure are implemented to reduce the risk of fractures. Possible
      interventions are essentially based on fall prevention and treatment of
      osteoporosis. Randomized clinical studies in the literature, in which it was
      studied the effect of anti-osteoporotic drugs in patients with MP showed a
      significant reduction in the number of fractures and increase BMD.

PMID- 22461824
TI  - The management of sacral stress fractures: current concepts.
AB  - Sacral stress fractures are an unusual but curable cause of low-back pain that
      should be considered in differential diagnosis, particularly in elderly
      osteoporotic patients. Rarely, they may occur in young women during the last
      trimester of pregnancy or a few weeks after delivery. Encompassing fatigue and
      insufficiency fractures, the occurrence of sacral stress fractures appears to be
      relatively under-reported, because of the general lack of awareness of this
      condition and the non-specificity of symptoms. Plain radiographs of the pelvis
      are the first exam performed but they are often inconclusive, whereas MRI and CT
      scans are the examinations of choice to establish the diagnosis. The purpose of
      this review is to increase awareness of this condition so that clinicians may
      consider sacral stress fracture in the differential diagnosis of low-back and
      pelvic pain, particularly in elderly patients without a history of trauma.

PMID- 22461825
TI  - Bone regeneration in dentistry.
AB  - The edentulism of the jaws and the periodontal disease represent conditions that
      frequently leads to disruption of the alveolar bone. The loss of the tooth and of
      its bone of support lead to the creation of crestal defects or situation of
      maxillary atrophy. The restoration of a functional condition involves the use of
      endosseous implants who require adequate bone volume, to deal with the
      masticatory load. In such situations the bone need to be regenerated, taking
      advantage of the biological principles of osteogenesis, osteoinduction and
      osteoconduction. Several techniques combine these principles with different
      results, due to the condition of the bone base on which we operate changes, the
      surgical technique that we use, and finally for the bone metabolic conditions of
      the patient who can be in a state of systemic osteopenia or osteoporosis; these
      can also affect the result of jaw bone reconstruction.

PMID- 22461826
TI  - Bazedoxifene: literature data and clinical evidence.
AB  - A Multidisciplinary National Panel of Experts in the management of Menopause and
      Postmenopausal Osteoporosis was created to determine the specific positioning of
      Bazedoxifene acetate (BZA), a third-generation selective estrogen receptor
      modulator (SERM), in the field of available therapeutic options in prevention and
      treatment of postmenopausal osteoporosis.There are various therapeutic options in
      prevention and treatment for postmenopausal osteoporosis, but nevertheless the
      problem of osteoporosis and osteoporosis-related fractures is not yet resolved
      today.In view of this unmet medical need, to have new treatments with efficacy
      and safety profile so good to therapeutically manage even larger groups of
      population is the conceptual basis to reduce the devastating impact of this
      disease on individual's morbidity and mortality, and on public health expense.The
      Panel has, moreover, pointed up the need to increase the awareness about the
      issue "osteopenia" as a risk factor for fracture to consider in daily clinical
      practice and the opportunity to evaluate fracture risk using an adequate
      algorithm (for example, FRAX(r), deFRA(r)), which integrates the result obtained
      by densitometry (Bone Mineral Density, BMD) (1, 2) and clinical risk factors, in
      order to consider threshold values for pharmacological intervention.As for
      prevention and treatment and different groups of age in women's life, it is
      evident as in the group ranging in age 50 to 65 years the reference Specialist
      may be the Gynecologist, as the Woman's doctor, even if other Specialists could
      be interested (Endocrinologist, Rheumatologist, Internist, General Practitioner,
      or other Specialist who is seeing a patient with osteopenia/osteoporosis). The
      involved Specialist, necessarily, has to make preventative and/or therapeutic
      strategies for osteopenia/osteoporosis.After the publication of the study Women's
      Health Initiative (WHI) in 2002 (3), there was a decrease in applying Hormonal
      Replacement Therapy (HRT) or Hormone Therapy (HT), that even if is prescribed for
      climacteric symptoms (hot flushes, night sweats, etc.) can prevent bone loss and
      reduce osteoporosis-related fracture risk. The lower use of HRT (HT) has
      increased and still increases the risk of developing, in postmenopausal women,
      osteopenia and osteoporosis, with increased fracture risk, as it is demonstrated
      by N.O.R.A. Study (National Osteoporosis Risk Assessment) published in 2004
      (4).On the other hand, the different treatments available for osteoporosis
      therapy, significantly decrease the relative risk of osteoporosis, but the
      percentage of non-treated or under-treated patients remains high. Thus, it is
      still fundamental to have at disposal further treatments with proven efficacy in
      preventing and treating osteopenia and osteoporosis in everyday clinical
      practice.

PMID- 22461827
TI  - Parmigiano Reggiano cheese and bone health.
AB  - Osteoporosis is a multifactorial disease characterized by loss of bone mass and
      microarchitectural deterioration of bone tissue, which leads to a consequent
      increase in the risk of skeletal fractures. Diet awakes a critical interest in
      osteoporosis, because it is one of the few determinants that can be safely
      modified. A healthy well balanced nutrition can play an important role in
      prevention and pathogenesis of osteoporosis, but also in support of a
      pharmacological therapy. Numerous evidences have already established that dietary
      calcium, proteins and vitamin D are essential nutrients for achieved peak bone
      mass and maintaining skeletal health.Dairy products, by providing both calcium
      and proteins, represent the optimal source of highly bioavailable nutrients for
      bone health. Among dairy foods in particular cheese results one of the major
      source of calcium in the adults western diet and also in the Italian adults
      diet.Parmigiano Reggiano cheese is an homemade Italian food whose denomination
      "Protected Designation of Origin" is linked to an artisanal manufacturing process
      in limited geographic area of Northern Italy and is an optimal source of
      essential nutrients for acquisition and maintenance of bone health. Parmigiano
      Reggiano is a cheese easy digested, for the presence of ready to use proteins and
      lipids, lactose free, rich in calcium, with possible prebiotic and probiotic
      effect. On the basis of its nutritional characteristics and of its easy
      digestibility Parmigiano Reggiano cheese is recommended in all feeding age
      groups.

PMID- 22461828
TI  - Prevalence of osteoporosis and vertebral fractures in acromegalic patients.
AB  - Growth Hormone (GH) and Insulin-like Growth Factor (IGF-1) stimulate
      proliferation, differentiation and extracellular matrix production in
      osteoblastic cells. GH and IGF-1 also stimulate recruitment and bone resorption
      activity in osteoclastic cells. A chronic systemic GH and IGF-1 excess produces
      an increased bone turn over in acromegalic patients (pts). Osteoporosis, joint
      alterations and bone deformities have a great clinical relevance in acromegalic
      pts and favour mortality and morbility. In the present study we evaluate the
      still unclear GH/IGF-1 activity on bone, Bone Mineral Density (BMD) and risk of
      osteoporotic Vertebral Fractures (VF), in relation to gender and gonadal status
      in acromegalic pts.Twenty acromegalic pts (12 F, 8 M) ranging 26-64 years were
      studied. Four pts were hypogonadic (1 F, 3 M), seven women were in post-menopause
      (PM) and four women eugonadic. The disease was active in twelve pts and inactive
      in eight pts. Serum and urinary 24/hrs calcium and phosphate and serum PTH, bone
      formation (P1NP) and resorption (beta-CTX) markers were assayed. BMD was measured
      using dual energy X ray absorptiometry (DXA) at the lumbar spine and femoral neck
      and bone quantitative ultrasonography (QUS) at phalanges. Osteoporotic VF were
      assessed by antero-posterior and lateral x-ray examinations of the thoracic and
      lumbar spine.Serum IGF-1, calcium and phosphate and 24-hours urinary calcium were
      significantly higher in pts with active disease in respect to pts with inactive
      disease. BMD was reduced in more of 50% of pts, in each skeletal sites measured.
      Z-score values were lower in males than in females. VF prevalence was 39% (43% in
      women, 57% in men). Fractured and non-fractured pts were not significantly
      different for BMD, T-score and Z-score.In conclusion, VF are frequent in
      acromegaly and, even mild and asymptomatic, play an important role on life
      quality and survival, already decreased in acromegalic pts. DXA and QUS methods
      are not sufficient for identifying pts at risk for fracture, due to the many
      possible interferences (bone deformities, osteoarthritis, joint rigidity and soft
      tissue tickening), since BMD is just one determinant of bone fracture. In the
      screening of acromegalic complications, it is necessary to perform a radiographic
      study of the spine at the time of diagnosis and during follow up.

PMID- 22461829
TI  - Osteoporosis in patients with subclinical hypothyroidism treated with thyroid
      hormone.
AB  - OBJECTIVE: to estimate the prevalence of osteoporosis in patients being treated
      with thyroid hormone. METHOD: cross-sectional retrospective study of primary care
      patients.  EXPERIMENTAL GROUP: patients diagnosed with subclinical hypothyroidism
      receiving thyroid hormone replacement therapy. CONTROL GROUP: patients not
      receiving replacement therapy. Once the sample was selected its members were
      summoned to complete a clinical questionnaire and undergo a bone density scan
      with a validated measuring device. The description of qualitative data was done
      in absolute frequencies and percentages and that of the quantitative data as mean
      standard deviation, median. In the comparison of qualitative data between groups
      we used the Chi-square test and contingency tables by rearranging the percentages
      of several variables. RESULTS: 182 patients were studied (112 experimental and 70
      control), diagnosed with subclinical hypothyroidism. The average age at diagnosis
      was 42.5 and 41.2 years, respectively. 32.7% and 33.2% were smokers. In the
      experimental group the coexistence of two or more cardiovascular risk factors was
      detected in 5.7% of the patients. Mean TSH was 6.67 mU/L, mean free T(4) 1,04
      ng/dl. 67% of the patients studied had some level of bone loss: 87% osteopenia
      and 14% osteoporosis. 56% of those suffering from bone less were women. With
      regard to the size of the thyroid hormone treatment, only 12% received 150
      MUg/day or more. 61% had received treatment for between 5 and 10 years and 19.5%
      for more than 10 years. CONCLUSIONS: there is a high prevalence of bone loss in
      patients with subclinical hypothyroidism treated with exogenous thyroxin.

PMID- 22461830
TI  - Neuropsychiatric disorders in hip fracture.
AB  - Hip fractures most frequently occur in the elderly population. They are mainly
      caused by falls from standing position. The presence of several comorbidities, in
      particular neuropsychiatric disorders, are related to high percentages of falls,
      disability and mortality rates. Delirium and depression are the two most common
      mental disorders in this population.Delirium is strongly related to an increase
      of functional limitation in activities of daily living, a decline in walking
      autonomy, and a higher rate of nursing home placement or death. A multi-factorial
      intervention program, consisting of oxygen supplementation, intravenous fluid
      supplementation and extra-nutrition, accurate monitoring of vital signs, adequate
      pain treatment, daily delirium screening, reduction in drug use, and modification
      in peri-operative management, should always be performed in good clinical
      practice.Patients who undergo surgery frequently experience depression that can
      worsening functional outcome. An early detection and an adequate intervention
      based on psychological support and pharmacological treatment can give good
      results.We propose a simple flow chart for the management of elderly hip fracture
      patients that should be used in both Orthopaedics and Rehabilitative settings.

PMID- 22461831
TI  - Updated incidence rates of fragility fractures in Italy: extension study 2002
      2008.
AB  - OBJECTIVES: We aimed to update the incidence rates of major fragility fractures
      in Italy, including those which do not result systematically in hospital
      admissions, on the basis of hospitalization rates provided in our previous
      researches. METHODS: We analyzed italian national hospital discharge data from
      year 2002 to 2008 in order to determine age- and sex-specific incidence rates of
      hip, vertebral, humeral, and forearm fractures occurred in people aged 40 to 100
      years of age. Re-hospitalizations of the same patients have been excluded from
      the analysis. Hospital discharge data have been adjusted taking into account
      recently published information concerning fracture-specific hospitalization
      rates. RESULTS: We estimated a total of 91,494 hip fractures in year 2008 among
      people aged 40 to 100 years old, with a +18.1% increase across the seven-year
      period. Women aged >75 years old (n=55,950) accounted for about 60% of total
      fractures observed both in males and females. Concerning males, the highest
      incidence was observed between 80 and 84 years old (about 5,000 hip fractures).
      Overall incidence rate per 100,000 inhabitants computed for hip fractures was
      283.5, with marked age- and sex-specific differences. Clinical vertebral
      fractures were estimated to be almost 61,000 in 2008, with a +6.3% increase over
      seven years. Overall incidence rate per 100,000 inhabitants computed for clinical
      vertebral fractures was 189.0, but this value doubled between 75 and 95 years of
      age. For the same year 2008, we estimated a total of 57,400 humeral and 94,000
      forearm/wrist fractures, with a +13.2% and +0.7% increase over the seven-year
      period, respectively. Overall humeral fractures incidence per 100,000 was
      estimated in 178.0, with highest rates (up to 600 and over) observed in women
      between 75 and 95 years of age, while incidence per 100,000 for wrist fractures
      was computed in 298.0, with top values observed in women between aged 55 years
      old and over. CONCLUSION: The burden of major osteoporotic fractures in Italy is
      still increasing. Preventive strategies aimed to reduce fractures incidence
      should be carried out at regional level.

PMID- 22461832
TI  - Compliance to antifracture treatments in Tuscany: a regional survey based on
      institutional pharmaceutical dataset.
AB  - OBJECTIVE: compliance to any antifracture therapy is the most important parameter
      affecting the effectiveness of the treatment. The aim of this study was to
      evaluate patients compliance to antifracture therapies in the whole Tuscany
      population who benefit from treatments reimbursed by the Regional Healthcare
      System. METHODS: we have analyzed all antifracture drug prescriptions recorded in
      Tuscany regional pharmaceutical database concerning year 2009, from both in
      hospital distribution database (direct drug delivery, FED), and private
      pharmacies across the whole region (SPF). Patients who started the treatment in
      2008 and those continuing it in 2010 were also considered in the analysis. The
      sample size consisted in 92,250 people (1:9 male to female ratio). Compliance to
      antifracture treatments at 3, 6, 9, and 12 months was analyzed by single drug
      (using the defined daily dose, DDD), and by age group (40-50, 50-60, 60-70, 70
      80, 90-100 years). RESULTS: patients compliance decreased under 80% after the
      first 3 months of treatment, reaching no more than 50% at 1 year. Our results
      show that compliance to antifracture treatments reflects the age of the patients.
      People aged 70-80 years old represent the age group most frequently treated with
      antifracture therapies (36.57% of total prescriptions), with alendronic acid
      being the most prescribed drug (29.73% of total drug prescribed). Monthly dosing
      did not increase compliance if compared to oral weekly regimens, while daily oral
      or s.c. dosing were associated to lower compliance rates. CONCLUSION: serious
      efforts need to be implemented to foster patients motivation in assuming their
      antifracture treatments for at least one year.

PMID- 22461833
TI  - Hypervitaminosis D: case report of pediatric osteoporosis secondary to cystic
      fibrosis.
AB  - The objective of the study is to evaluate alterations of bone metabolism in
      adolescence and adult CF, determining the rate of osteoporosis, osteopenia and
      vertebral and non-vertebral fractures. We took into account the clinical case of
      a child who right from the age of seven years has presented joint pain.The little
      girl was diagnosed with osteopenia taken with therapy of calcium and vitamin D;
      after few years despite treatment nephrocalcinosis and osteoporosis take over.It
      was examined a cohort of patients with cystic fibrosis of the southern Italy, 24
      patients aged between 12 and 44 years, 12 females and 12 males with BMD
      assessment methods like dual energy X-rays (DXA) and calcaneal ultrasound
      densitometry in a few cases, ultrasonography was used jointly.From this case
      study we tried to establish the relationship between cystic fibrosis and
      osteoporosis etiopathogenetic, the adoptive therapy and the impact of therapies
      on patients.It was concluded that, given the high number of unrecognized patients
      with impaired bone mineralization, we must implement and integrate a more
      aggressive treatment with bisphosphonates and prevention programs that can combat
      the lifestyle and new eating habits of our young people that facilitate the loss
      of bone mass.

PMID- 22461834
TI  - When the art popularized orthopaedic science.

PMID- 22461835
TI  - Interplay of polarity proteins and GTPases in T-lymphocyte function.
AB  - Polarity refers to the asymmetric distribution of different cellular components
      within a cell and is central to many cell functions. In T-cells, polarity
      regulates the activation, migration, and effector function of cytotoxic T-cells
      (CTLs) during an immune response. The regulation of asymmetric cell division by
      polarity proteins may also dictate CTL effector and memory differentiation
      following antigen presentation. Small GTPases, along with their associated
      polarity and adaptor proteins, are critical for mediating the polarity changes
      necessary for T-cell activation and function, and in turn, are regulated by
      guanine exchange factors (GEFS) and GTPase activating proteins (GAPS). For
      example, a novel GEF, dedicator of cytokinesis 8 (DOCK8) was recently identified
      as a regulator of immune cell function and mutations in DOCK8 have been detected
      in patients with severe combined immunodeficiency. Both B and T-cells from DOCK8
      mutant mice form defective immunological synapses and have abnormal functions, in
      addition to impaired immune memory development. This paper will discuss the
      interplay between polarity proteins and GTPases, and their role in T-cell
      function.

PMID- 22461836
TI  - Hamster and murine models of severe destructive Lyme arthritis.
AB  - Arthritis is a frequent complication of infection in humans with Borrelia
      burgdorferi. Weeks to months following the onset of Lyme borreliosis, a
      histopathological reaction characteristic of synovitis including bone, joint,
      muscle, or tendon pain may occur. A subpopulation of patients may progress to a
      chronic, debilitating arthritis months to years after infection which has been
      classified as severe destructive Lyme arthritis. This arthritis involves focal
      bone erosion and destruction of articular cartilage. Hamsters and mice are animal
      models that have been utilized to study articular manifestations of Lyme
      borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a
      transient synovitis. However, severe destructive Lyme arthritis can be induced by
      infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated
      hamsters, mice, and interferon-gamma- (IFN-gamma-) deficient mice with viable B.
      burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates
      easy assessment of Lyme borreliosis vaccine preparations for deleterious effects
      while murine models of severe destructive Lyme arthritis allow for investigation
      of mechanisms of immunopathology.

PMID- 22461837
TI  - Influence of dendritic cells on B-cell responses during HIV infection.
AB  - Dendritic cells (DCs) modulate B-cell differentiation, activation, and survival
      mainly through production of growth factors such as B lymphocyte stimulator
      (BLyS/BAFF). DC populations have been reported to be affected in number,
      phenotype and function during HIV infection and such alterations may contribute
      to the dysregulation of the B-cell compartment. Herein, we reflect on the
      potential impact of DC on the pathogenesis of HIV-related B cell disorders, and
      how DC status may modulate the outcome of mucosal B cell responses against HIV,
      which are pivotal to the control of disease. A concept that could be extrapolated
      to the overall outcome of HIV disease, whereby control versus progression may
      reside in the host's capacity to maintain DC homeostasis at mucosal sites, where
      DC populations present an inherent capacity of modulating the balance between
      tolerance and protection, and are amongst the earliest cell types to be exposed
      to the virus.

PMID- 22461838
TI  - Transcription expression and clinical significance of dishevelled-3 mRNA and
      delta-catenin mRNA in pleural effusions from patients with lung cancer.
AB  - OBJECTIVE: To evaluate diagnostic utility of Dishevelled-3 (DVL-3) mRNA and delta
      catenin mRNA expression in pleural effusions of patients with lung cancer.
      METHODS: DVL-3 mRNA and delta-catenin mRNA levels were assessed by performing RT
      PCR on pleural effusion specimens from patients with lung cancer (n = 75) and
      with lung benign disease (n = 51). RESULTS: The expressions of DVL-3 mRNA and
      delta-catenin mRNA were significantly higher in malignant than in benign lung
      disease (P < 0.01) and were obviously higher than cytology in adenocarcinoma (P <
      0.01). In single use, DVL-3 mRNA had the highest specificity (94.1%) and PPV
      (95.7%), whereas delta-catenin mRNA had the highest sensitivity (92.0%) and NPV
      (88.5%). When combinations of markers were evaluated together, DVL-3 mRNA and
      delta-catenin mRNA gave a high-diagnostic performance: sensitivity of 100.0%, NPV
      of 100.0%, and accuracy of 96.0%, respectively. CONCLUSION: As molecular markers
      of detecting pleural micrometastasis, DVL-3 mRNA and delta-catenin mRNA are
      helpful to diagnose the cancer cells in pleural effusions of patients with lung
      cancer.

PMID- 22461839
TI  - Antiangiogenic Effects and Therapeutic Targets of Azadirachta indica Leaf Extract
      in Endothelial Cells.
AB  - Azadirachta indica (common name: neem) leaves have been found to possess
      immunomodulatory, anti-inflammatory and anti-carcinogenic properties. The present
      study evaluates anti-angiogenic potential of ethanol extract of neem leaves
      (EENL) in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs
      with EENL inhibited VEGF induced angiogenic response in vitro and in vivo. The in
      vitro proliferation, invasion and migration of HUVECs were suppressed with EENL.
      Nuclear fragmentation and abnormally small mitochondria with dilated cristae were
      observed in EENL treated HUVECs by transmission electron microscopy. Genome-wide
      mRNA expression profiling after treatment with EENL revealed differentially
      regulated genes. Expression changes of the genes were validated by quantitative
      real-time polymerase chain reaction. Additionally, increase in the expression of
      HMOX1, ATF3 and EGR1 proteins were determined by immunoblotting. Analysis of the
      compounds in the EENL by mass spectrometry suggests the presence of nimbolide,
      2',3'-dehydrosalannol, 6-desacetyl nimbinene and nimolinone. We further confirmed
      antiproliferative activity of nimbolide and 2',3'-dehydrosalannol in HUVECs. Our
      results suggest that EENL by regulating the genes involved in cellular
      development and cell death functions could control cell proliferation, attenuate
      the stimulatory effects of VEGF and exert antiangiogenic effects. EENL treatment
      could have a potential therapeutic role during cancer progression.

PMID- 22461840
TI  - Acupuncture Improves Sleep Conditions of Minipigs Representing Diurnal Animals
      through an Anatomically Similar Point to the Acupoint (GV20) Effective for
      Humans.
AB  - Acupuncture, an alternative medicine, has been widely applied for people with
      sleep disturbances; therefore, the effects should be evaluated objectively. Micro
      minipigs (MMPigs), the smallest miniature pigs for animal experiments, were used.
      Acupuncture was performed at two different points: Dafengmen is located on the
      head and is an anatomically similar point to human-Baihui (GV20), an effective
      acupoint for sleep disturbances in humans; pig-Baihui is on the back. The
      procedure was performed as follows: shallow, within 5 mm depth for several
      seconds; deep, 10-20 mm depth for 20 min. The sleep conditions were evaluated by
      actigraph, and the amount of catecholamine in pooled urine after acupuncture
      treatment. MMPigs with deep acupuncture at Dafengmen showed significantly
      efficient values on actigraph and catecholamine analysis as compared with
      untreated MMPigs. The effective acupoint for sleep conditions in the porcine
      model is at an anatomically similar point to humans, rather than the point
      determined by traditional Chinese medicine.

PMID- 22461841
TI  - Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20 In Vitro and In
      Vivo.
AB  - Irritable bowel syndrome (IBS) is a functional bowel disorder and the etiology is
      not well understood. Currently there is no cure for IBS and no existing
      medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese
      medicinal formula that offers beneficial effects in patients with IBS; however,
      the underlying mechanisms are largely unknown. This study showed that IBS-20
      potently inhibited LPS- or IFNGamma-stimulated expression of pro-inflammatory
      cytokines, as well as classically activated macrophage marker nitric oxide
      synthase 2. Similarly, IBS-20 or the component herb Coptis chinensis decreased
      LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells.
      IBS-20 or the component herbs also blocked or attenuated the IFNGamma-induced
      drop in transepithelial electric resistance, an index of permeability, in fully
      differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory
      cytokines in inflamed colon from TNBS-treated mice was suppressed significantly
      by orally administrated IBS-20, including IFNGamma and IL-12p40. These data
      indicate that the anti-inflammatory activities of IBS-20 may contribute to the
      beneficial effects of the herbal extract in patients with IBS, providing a
      potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential
      therapeutic agent against other Th1-dominant gut pathologies such as inflammatory
      bowel disease.

PMID- 22461842
TI  - Auricular Acupuncture May Suppress Epileptic Seizures via Activating the
      Parasympathetic Nervous System: A Hypothesis Based on Innovative Methods.
AB  - Auricular acupuncture is a diagnostic and treatment system based on normalizing
      the body's dysfunction. An increasing number of studies have demonstrated that
      auricular acupuncture has a significant effect on inducing parasympathetic tone.
      Epilepsy is a neurological disorder consisting of recurrent seizures resulting
      from excessive, uncontrolled electrical activity in the brain. Autonomic
      imbalance demonstrating an increased sympathetic activity and a reduced
      parasympathetic activation is involved in the development and progress of
      epileptic seizures. Activation of the parasympathetic nervous system such as
      vagus nerve stimulation has been used for the treatment of intractable epilepsy.
      Here, we propose that auricular acupuncture may suppress epileptic seizures via
      activating the parasympathetic nervous system.

PMID- 22461843
TI  - Copaiba oil-resin treatment is neuroprotective and reduces neutrophil recruitment
      and microglia activation after motor cortex excitotoxic injury.
AB  - The oil-resin of Copaifera reticulata Ducke is used in the Brazilian folk
      medicine as an anti-inflammatory and healing agent. However, there are no
      investigations on the possible anti-inflammatory and neuroprotective roles of
      copaiba oil-resin (COR) after neural disorders. We have investigated the anti
      inflammatory and neuroprotective effects of COR following an acute damage to the
      motor cortex of adult rats. Animals were injected with the neurotoxin N-Methyl-D
      Aspartate (NMDA) (n = 10) and treated with a single dose of COR (400 mg/kg, i.p.)
      soon after surgery (Group 1) or with two daily doses (200 mg/kg, i.p.) during 3
      days (Group 2) alter injury. Control animals were treated with vehicle only. COR
      treatment induced tissue preservation and decreased the recruitment of
      neutrophils and microglial activation in the injury site compared to vehicle
      animals. The results suggest that COR treatment induces neuroprotection by
      modulating inflammatory response following an acute damage to the central nervous
      system.

PMID- 22461844
TI  - Higuchi fractal properties of onset epilepsy electroencephalogram.
AB  - Epilepsy is a medical term which indicates a common neurological disorder
      characterized by seizures, because of abnormal neuronal activity. This leads to
      unconsciousness or even a convulsion. The possible etiologies should be evaluated
      and treated. Therefore, it is necessary to concentrate not only on finding out
      efficient treatment methods, but also on developing algorithm to support
      diagnosis. Currently, there are a number of algorithms, especially nonlinear
      algorithms. However, those algorithms have some difficulties one of which is the
      impact of noise on the results. In this paper, in addition to the use of fractal
      dimension as a principal tool to diagnose epilepsy, the combination between ICA
      algorithm and averaging filter at the preprocessing step leads to some positive
      results. The combination which improved the fractal algorithm become robust with
      noise on EEG signals. As a result, we can see clearly fractal properties in
      preictal and ictal period so as to epileptic diagnosis.

PMID- 22461845
TI  - Decimative spectral estimation with unconstrained model order.
AB  - This paper presents a new state-space method for spectral estimation that
      performs decimation by any factor, it makes use of the full set of data and
      brings further apart the poles under consideration, while imposing almost no
      constraints to the size of the Hankel matrix (model order), as decimation
      increases. It is compared against two previously proposed techniques for spectral
      estimation (along with derived decimative versions), that lie among the most
      promising methods in the field of spectroscopy, where accuracy of parameter
      estimation is of utmost importance. Moreover, it is compared against a state-of
      the-art purely decimative method proposed in literature. Experiments performed on
      simulated NMR signals prove the new method to be more robust, especially for low
      signal-to-noise ratio.

PMID- 22461846
TI  - Knowledge, attitudes and perceptions of health professionals in relation to
      A/H1N1 influenza and its vaccine.
AB  - OBJECTIVE: To determine the intention of health professionals, doctors and
      nurses, concerning whether or not to be vaccinated against A/H1N1 influenza
      virus, and their perception of the severity of this pandemic compared with
      seasonal flu. MATERIAL AND METHODS: A cross-sectional study was carried out based
      on an questionnaire e-mailed to health professionals in public healthcare centres
      in Vitoria between 6 and 16 November 2009; the percentage of respondents who
      wanted to be vaccinated and who perceived the pandemic flu to carry a high risk
      of death were calculated. RESULTS: A total of 115 people completed the
      questionnaire of whom 61.7% (n=71) were doctors and 38.3% (n=44) were nurses. Of
      these, 33.3% (n=23) of doctors and 13.6% (n=6) of nurses intended to be
      vaccinated (p=0.019). Even among those who considered themselves to be at a high
      risk, 70.6% (n=48) of doctors and 31.7% (n=13) of nurses participating in the
      study (p=0.001) planned to have the vaccination. CONCLUSIONS: Most health
      professionals, and in particular nurses, had no intention to be vaccinated
      against A/H1N1 influenza virus at the beginning of the vaccination campaign.

PMID- 22461847
TI  - Optimism of health care workers during a disaster: a review of the literature.
AB  - Optimism has several orientations. One such outlook is a general tendency to
      regard the world as a positive place, accepting difficulties as mere challenges
      instead of impassable barriers. Among health care workers, optimism improves
      their level of functioning, their patients' satisfaction, and their therapeutic
      results. Optimistic staff members report feeling less pressure, use fewer
      avoidance strategies, focus on practical problem solutions, seek social support,
      and have more trust in people and organizations. The aim of this article is to
      provide a review of the literature concerning the role of optimism, both in daily
      life and in crisis situations. An attempt was made to find the linkage between
      optimism among health care workers during disasters and their active response,
      with special emphasis on the relationship between optimism and knowledge,
      feelings or behavior. Based on the literature, optimism was found to be helpful
      both in daily medical work and in cases of medical emergencies. Optimism was also
      revealed one of the key components of resilience and self-efficacy. Therefore, it
      is recommended to consider strengthening the optimism through initiative
      programs. Obtaining optimism can be included in toolkit preparedness for health
      care workers in order to confront the complications in the aftermath of disaster.
      These programs, together with appropriate information, social support,
      professional trust, and leaders modeling behavior, will raise the well-being and
      enhance coping skills of the health care workers during and aftermath of disaster
      scenarios.

PMID- 22461848
TI  - Tetanus seropositive prevalence and perceived protection from emergency
      admissions.
AB  - BACKGROUND: Emergency physicians see many people who present to the emergency
      department stating that they are immunized against tetanus, when in fact, they
      are not. The patient history is not dependable for determining true tetanus
      status and simple patient surveys do not provide actual prevalence. The objective
      of this study was to determine the prevalence of tetanus status by antibody titer
      seropositivity and quantify such status among patients reporting tetanus
      protection. METHODS: This study is a single center prospective convenience sample
      of patients presenting to the emergency department 12 years of age or older.
      Patients deemed study candidates and willing to be in the study filled out an
      eight-question questionnaire that included the question 'is your tetanus shot up
      to date'. A blood sample was then drawn for tetanus antibody titer and quantified
      according to a pre-determined cutoff for protection. RESULTS: A total of 163
      patients were enrolled. Of patients responding yes to the query 'is your tetanus
      shot up to date' 12.8% (N=5) of them were not seropositive. Of the 26 people who
      were seronegative in the study all had been to a doctor in the past year and
      88.5% (N=23) had been to their family physician. CONCLUSION: The study suggests
      that it may be difficult to trust the tetanus immunization history given by
      patients presenting to the emergency room. The study also observed that a large
      percentage of patients who were serenegative were seen by a primary care
      physician and not had a necessary tetanus immunization.

PMID- 22461849
TI  - Logistic support provided to Australian disaster medical assistance teams:
      results of a national survey of team members.
AB  - BACKGROUND: It is likely that calls for disaster medical assistance teams (DMATs)
      continue in response to international disasters. As part of a national survey,
      the present study was designed to evaluate the Australian DMAT experience and the
      need for logistic support. METHODS: Data were collected via an anonymous mailed
      survey distributed via State and Territory representatives on the Australian
      Health Protection Committee, who identified team members associated with
      Australian DMAT deployments from the 2004 Asian Tsunami disaster. RESULTS: The
      response rate for this survey was 50% (59/118). Most of the personnel had
      deployed to the South East Asian Tsunami affected areas. The DMAT members had
      significant clinical and international experience. There was unanimous support
      for dedicated logistic support with 80% (47/59) strongly agreeing. Only one
      respondent (2%) disagreed with teams being self sufficient for a minimum of 72
      hours. Most felt that transport around the site was not a problem (59%; 35/59),
      however, 34% (20/59) felt that transport to the site itself was problematic. Only
      37% (22/59) felt that pre-deployment information was accurate. Communication with
      local health providers and other agencies was felt to be adequate by 53% (31/59)
      and 47% (28/59) respectively, while only 28% (17/59) felt that documentation
      methods were easy to use and reliable. Less than half (47%; 28/59) felt that
      equipment could be moved easily between areas by team members and 37% (22/59)
      that packaging enabled materials to be found easily. The maximum safe container
      weight was felt to be between 20 and 40 kg by 58% (34/59). CONCLUSIONS: This
      study emphasises the importance of dedicated logistic support for DMAT and the
      need for teams to be self sufficient for a minimum period of 72 hours. There is a
      need for accurate pre deployment information to guide resource prioritisation
      with clearly labelled pre packaging to assist access on site. Container weights
      should be restricted to between 20 and 40 kg, which would assist transport around
      the site, while transport to the site was seen as problematic. There was also
      support for training of all team members in use of basic equipment such as
      communications equipment, tents and shelters and water purification systems.

PMID- 22461850
TI  - Is it reliable to assess visual attention of drivers affected by Parkinson's
      disease from the backseat?-a simulator study.
AB  - BACKGROUND: Current methods of determining licence retainment or cancellation is
      through on-road driving tests. Previous research has shown that occupational
      therapists frequently assess drivers' visual attention while sitting in the back
      seat on the opposite side of the driver. Since the eyes of the driver are not
      always visible, assessment by eye contact becomes problematic. Such procedural
      drawbacks may challenge validity and reliability of the visual attention
      assessments. In terms of correctly classified attention, the aim of the study was
      to establish the accuracy and the inter-rater reliability of driving assessments
      of visual attention from the back seat. Furthermore, by establishing eye contact
      between the assessor and the driver through an additional mirror on the wind
      screen, the present study aimed to establish how much such an intervention would
      enhance the accuracy of the visual attention assessment. METHODS: Two drivers
      with Parkinson's disease (PD) and six control drivers drove a fixed route in a
      driving simulator while wearing a head mounted eye tracker. The eye tracker data
      showed where the foveal visual attention actually was directed. These data were
      time stamped and compared with the simultaneous manual scoring of the visual
      attention of the drivers. In four of the drivers, one with Parkinson's disease, a
      mirror on the windscreen was set up to arrange for eye contact between the driver
      and the assessor. Inter-rater reliability was performed with one of the Parkinson
      drivers driving, but without the mirror. RESULTS: Without mirror, the overall
      accuracy was 56% when assessing the three control drivers and with mirror 83%.
      However, for the PD driver without mirror the accuracy was 94%, whereas for the
      PD driver with a mirror the accuracy was 90%. With respect to the inter-rater
      reliability, a 73% agreement was found. CONCLUSION: If the final outcome of a
      driving assessment is dependent on the subcategory of a protocol assessing visual
      attention, we suggest the use of an additional mirror to establish eye contact
      between the assessor and the driver. The clinicians' observations on-road should
      not be a standalone assessment in driving assessments. Instead, eye trackers
      should be employed for further analyses and correlation in cases where there is
      doubt about a driver's attention.

PMID- 22461851
TI  - Recurrent nausea, vomiting and abdominal pain due to hypothyroidism.
AB  - A 45-year-old woman presented with recurrent episodes of diarrhoea, nausea,
      vomiting and abdominal pain. Investigations, including routine blood tests,
      gastroscopy with duodenal biopsy, colonoscopy and abdominal computed tomography
      (CT) scanning, failed to find a cause of these symptoms. Routine blood tests were
      repeated and included thyroid function tests. The latter confirmed a diagnosis of
      primary hypothyroidism. After initiating thyroid hormone replacement therapy, all
      of the patient's symptoms resolved. She remains well and asymptomatic to date.

PMID- 22461852
TI  - Early mobilisation of intensive care unit patient: the challenges of morbid
      obesity and multiorgan failure.
AB  - A 44-year-old morbidly obese (body mass index 69 kg/m(2)) woman presented to our
      medical intensive care unit (ICU) with septic shock and multiorgan failure
      requiring mechanical ventilation, a vasopressor infusion, and haemodialysis.
      Before this admission, the patient reported being able to ambulate approximately
      3 m with a walker. Intensive physical therapy was started on ICU day 2, and the
      patient was successfully mobilised throughout her ICU stay despite the extreme
      challenges posed by her morbid obesity and critical illness. After only a 9 day
      stay, the patient was discharged directly home from the medical ICU, walking a
      total distance of 37 m in a single physical therapy session.

PMID- 22461853
TI  - Cushing's syndrome and big IGF-II associated hypoglycaemia in a patient with
      adrenocortical carcinoma.
AB  - A 41-year-old woman had a general health examination and was diagnosed with a non
      functioning adrenocortical carcinoma (ACC). Despite surgery and chemotherapy with
      mitotane, the ACC progressed with metastases to the lymph nodes, liver and lung.
      Initially, she developed adrenal insufficiency and was treated with
      hydrocortisone. As the ACC progressed, it produced superabundant cortisol,
      resulting in clinically overt Cushing's syndrome. As the liver metastases grew,
      the patient developed hypoglycaemia with suppression of endogenous insulin
      secretion. She had to be given large quantities of glucose intravenously to
      remain normoglycaemic. The serum insulin-like growth factor (IGF)-II/IGF-I ratio
      had increased to 84. We identified big IGF-II, a primary hormonal mediator of non
      islet cell tumour hypoglycaemia (NICTH), in the serum and tumour using western
      blotting. This is the first case of ACC that showed both Cushing's syndrome and
      NICTH associated with big IGF-II.

PMID- 22461854
TI  - Perforation of Meckel's diverticulum secondary to a large faecolith.
AB  - A 79-year-old woman presented with a 4 day history of central abdominal pain and
      vomiting. Clinical examination revealed a distended abdomen with predominantly
      right sided tenderness. Following an initial period of supportive treatment
      pending further imaging, evolving abdominal signs became evident. Based on the
      suspicion of a perforated hollow viscus, an emergency laparotomy was carried out.
      Operative findings were of a Meckel's diverticulum with evidence of pressure
      necrosis and perforation near its apex, which was distended due to a 6 cm
      faecolith. Resection and primary anastomosis was performed. Despite a lower
      respiratory tract infection, the patient was deemed clinically stable enough to
      be discharged on the 24th postoperative day.

PMID- 22461855
TI  - Intravitreal bevacizumab (Avastin) associated with secondary hyphaema in a case
      of proliferative sickle cell retinopathy.
AB  - Intravitreal bevacizumab (Avastin) has been used off label for various
      conditions, including proliferative sickle cell retinopathy (PSR). Some authors
      have reported a more rapid resolution of the vitreous haemorrhage in Goldberg
      stage 4 PSR. Following injection of 1.25 mg of bevacizumab in each eye in a case
      of PSR (right eye with stage 3 sea fan neovascularisation and left eye with
      organising vitreous haemorrhage), we recently found a surprising association with
      significant secondary hyphaema on the fifth day post injection in the eye with
      vitreous haemorrhage. After 4 weeks, there was a dramatic fibrotic resolution of
      the stage 3 sea fan in the other eye. Systemic bevacizumab as used in the
      management of colorectal cancer has been associated with bleeding diathesis in
      some cases, as well as with deep venous thrombosis. The rheological profile of
      bevacizumab is not clear-cut at the moment and the drug should therefore be used
      with caution in cases of stage 4 PSR.

PMID- 22461856
TI  - Perforation of sigmoid diverticulum following endoscopic polypectomy of an
      adenoma.
AB  - Colonic polyps or carcinomas located within a colonic diverticulum are very rare
      phenomena. There are a few reports in the literature describing adenocarcinoma
      arising within colonic diverticulum. Endoscopic resection of the polyp poses a
      risk of perforation because of the lack of muscular coats in the diverticulum.
      Therefore, special care should be taken in the treatment of such patients.

PMID- 22461857
TI  - Sudden death due to medulloblastoma.
AB  - Intracranial tumours can be accompanied with intracerebral and intracerebellar
      non-traumatic haemorrhage; in some cases, this might be their first clinical
      sign. We report a case of a man who suffered sudden death due to medulloblastoma,
      with intratumoral haemorrhage; his tumour had a hemispheric cerebellar
      positioning. The cerebral oedema seen at autopsy reflected the immediate
      cessation of cerebral vascular circulation, leading to sudden death. Acute
      obstructive hydrocephaly is a mechanism widely known in the literature for
      causing sudden death.

PMID- 22461858
TI  - Unusual underlying cause of recurrent vulval abscess.
AB  - An ex-intravenous drug user was admitted four times during a 2 year period from
      December 2006, with the same complaint of vulval abscess which required repeat
      incision and drainage procedures. In January 2009, a pelvic x-ray showed widening
      of the symphysis pubis, marginal irregularities, and severe erosive changes which
      were consistent with pubic osteomyelitis. She was treated with intravenous
      ciprofloxacin and clindamycin for 2 weeks and was discharged on oral antibiotics
      for 6 weeks. She recovered well and her condition has significantly improved with
      no recurrent infection so far. She is now being followed up every 4-6 weeks at
      the orthopaedics outpatient clinic.

PMID- 22461859
TI  - Gene Therapy for Pain: A Perspective.

PMID- 22461860
TI  - Innate and procured immunity inside the digestive tract of the medicinal leech.
AB  - Especially when combined with unique biological adaptations, invertebrate animals
      provide important insights into innate immunity because the immune response is
      not complicated by adaptive immunity that vertebrates evolved. One such example
      is the digestive tract of the medicinal leech, Hirudo verbana, which is unusual
      in two aspects, it contains a simple microbial community and it stores large
      amounts of vertebrate blood for a several months. In this review we will discuss
      aspects of the innate immunity of the leech and from the ingested blood that we
      term procured immunity to differentiate it from the immunity encoded by the leech
      genome.

PMID- 22461861
TI  - Population aging and hospitalization for chronic disease in Germany.
AB  - BACKGROUND: The population of Germany is aging, i.e., the elderly currently make
      up an increasing percentage of the population from year to year. Furthermore,
      many common chronic diseases mainly affect the elderly. For these two reasons,
      the overall cost of health care in Germany is expected to increase. We studied
      the effect that population aging has had on the number of hospitalizations for
      major types of chronic disease in Germany since the year 2000. METHODS: This
      study is based on nationwide hospitalization statistics, classified by diagnosis,
      that were published by the German Federal Statistical Office. We analyzed data
      for three classes of diagnoses--malignant neoplasia, cardiovascular diseases, and
      diseases of the musculoskeletal system and connective tissue--which were further
      broken down into nine diagnostic subgroups. Changes in inpatient case numbers
      might be due either to population aging or to changing rates of hospitalization
      for individual diagnoses. We used index decomposition analysis to determine the
      relative influence of these two factors on changing case numbers. RESULTS: The
      author found that the aging of the population increased the number of
      hospitalizations for all of the diagnoses studied. This was particularly evident
      with respect to the large birth cohorts born in the 1920s (with the diagnosis of
      congestive heart failure) and in the period 1934-1944 (with the diagnoses
      ischemic heart disease, lung cancer, colorectal cancer, and osteoarthritis). On
      the other hand, changing rates of hospitalization for individual diagnoses
      increased the number of hospitalizations for some diagnoses (congestive heart
      failure, diseases of the spine and back) and decreased it for others (ischemic
      heart disease, cerebrovascular diseases, colorectal cancer, breast cancer).
      CONCLUSION: The aging of the population and the changing rates of hospitalization
      for various diagnoses are exerting separate effects on the number of
      hospitalizations for chronic diseases in Germany. Predictions of hospital case
      numbers in the future must take both factors into account.

PMID- 22461862
TI  - Hysterectomy is mostly unnecessary.

PMID- 22461863
TI  - Data not correctly calculated.

PMID- 22461864
TI  - Outpatient hysterectomies were not included.

PMID- 22461867
TI  - Pharmacogenomics: the right drug to the right person.
AB  - Pharmacogenomics is the branch of pharmacology which deals with the influence of
      genetic variation on drug response in patients by correlating gene expression or
      single-nucleotide polymorphisms with a drug's efficacy or toxicity. It aims to
      develop rational means to optimize drug therapy, with respect to the patients
      genotype, to ensure maximum efficacy with minimal adverse effects. Such
      approaches promise the advent of personalized medicine, in which drugs and drug
      combinations are optimized for each individual's unique genetic makeup.
      Pharmacogenomics is the whole genome application of pharmacogenetics, which
      examines the single gene interactions with drugs. KEYWORDS: Pharmacogenetics;
      Single nucleotide polymorphisms; Genomics; Genotype.

PMID- 22461868
TI  - Introducing a Chair-Side Novel Approach to Reach Evidence-based Periodontal
      Information in the Daily Periodontal Practice.
AB  - BACKGROUND: Evidence-based healthcare is not an easier approach to patient
      management, but should provide both clinicians and patients with greater
      confidence and trust in their mutual relationship. The intellectual embrace of
      evidence-based methods, coupled with clinical expertise and consideration of the
      patients individual uniqueness and requirements, is needed for all periodontal
      therapists if optimum care is the goal. One important element of evidence-based
      decision making in periodontology is the systematic review. Systematic reviews
      usually provide the periodontist with the highest level of evidence which should
      be taken into consideration when constructing any treatment plan in the dental
      clinic. However, reaching systematic reviews might be a time-consuming procedure
      that needs further personal skills. METHODS: In this paper, a chair-side novel
      approach to facilitate the incorporation of systematic reviews into daily
      periodontal practice is presented. It is based on three simple tools, namely, a
      list of suitable periodontics-related key words, a data bank of all up-to-date
      published systematic reviews in periodontology, and hand-made paper sheets to
      match the key words with their related systematic review statements. RESULTS AND
      CONCLUSIONS: A primary validation of this method indicated the simplicity in
      learning and application. KEYWORDS: Chair-side; Evidence-based medicine;
      Periodontology; Systematic review.

PMID- 22461866
TI  - Cancer-related fatigue: epidemiology, pathogenesis, diagnosis, and treatment.
AB  - BACKGROUND: Many cancer patients suffer from cancer-related fatigue (CRF) both
      during and after their treatment. CRF can arise at any point in the course of the
      disease and can be either self-limited or persistent, sometimes for years. It
      gives rise to a vicious circle of impaired physical performance, avoidance of
      exertion, inactivity, inadequate physical recovery, helplessness, and depressed
      mood. Its hallmarks are tiredness, exhaustion, and lack of energy; it can impair
      performance so severely that the patient is unable to work. It is associated with
      increased mortality. Cancer patients are hardly ever systematically asked about
      the symptoms and signs of CRF. The stress and impairments that it produces are
      often inadequately appreciated, and the opportunities for treatment often
      neglected. METHOD: Selective review of the pertinent literature, including
      published guidelines from Germany and abroad. RESULTS: The pathogenesis of CRF is
      complex, involving an interaction of somatic, emotional, cognitive, and
      psychosocial factors, with a highly variable pattern of clinical expression.
      Clinical history-taking plays a key role in diagnostic assessment. Depressive
      disorders must be considered in the differential diagnosis. Many randomized
      trials and meta-analyses have documented the efficacy of pharmacological and non
      pharmacological treatments for CRF. CONCLUSION: Cancer-related fatigue is a
      serious problem that impairs patients physically, mentally, and socially.
      Physicians need to know how to recognize and treat it.

PMID- 22461869
TI  - Residual Cognitive Deficit in Adults with Depression who Recovered after 6-month
      Treatment: Stable versus State-Dependent Markers.
AB  - BACKGROUND: Knowledge of depression-related disturbances in cognitive functioning
      is advancing, but little is known about the cognitive response to treatment for
      major depression, especially in younger adults. This study investigated the
      deficits in multiple cognitive domains in middle-aged patients with major
      depressive disorder (MDD), using a prospective follow-up study design. METHODS:
      The sample consisted of 13 medication-free MDD patients and 13 education- and age
      matched healthy controls. All subjects were administered clinical measures as
      well as a comprehensive neurocognitive test battery aimed at assessing multiple
      cognitive domains at the time of recruitment. Patients remitted after 6 months
      following treatment repeated the neurocognitive assessment. RESULTS: There were
      significant differences between the depressed subjects and controls at baseline.
      MDD patients with remitted symptoms still showed significant deficits in
      executive function and motor function, but not in memory or attention domains.
      Patients had significant improvement in memory and attention domains only, once
      their depressive symptoms had subsided; while executive functioning as well as
      motor functioning remained unchanged. CONCLUSIONS: Executive functioning and
      motor functioning deficits might be stable vulnerability indicators for MDD, and
      memory and attention impairment might serve as state-dependent indicators for
      MDD. KEYWORDS: Major depressive disorder; Remission; Residual; Cognitive
      deficits; Follow-up.

PMID- 22461870
TI  - Burnout among the clinical dental students in the jordanian universities.
AB  - BACKGROUND: The study aimed to evaluate the level of burnout among the clinical
      dental students in two Jordanian universities. METHODS: A total of 307 students
      from the two schools were surveyed using Maslach Burnout Inventory survey. Scores
      for the inventory's subscales were calculated and the mean values for the
      students' groups were computed separately. Kruskal-Wallis and Mann-Whitney tests
      were carried out and the results were compared at 95% confidence level. RESULTS:
      The results showed that the dental students in both Jordanian universities
      suffered high levels of emotional exhaustion and depersonalization compared to
      reported levels for dental students in other countries. The dental students of
      the University of Jordan demonstrated a significantly higher (p < 0.05) level of
      emotional exhaustion than their counterparts in the Jordan University of Science
      and Technology. CONCLUSIONS: The findings indicated that dental students in the
      Jordanian universities presented considerable degrees of burnout manifested by
      high levels of emotional exhaustion and depersonalization. Studies targeting
      students health and psychology should be carried out to determine the causes of
      burnout among dental students. The curricula of the dental schools in the two
      universities should be accordingly improved to minimize burnout among the
      students. KEYWORDS: Burnout; Emotional exhaustion; Depersonalization; Personal
      accomplishment; Maslach Burnout Inventory.

PMID- 22461871
TI  - Studies on genomic DNA stability in aluminium-maltolate treated aged new zealand
      rabbit: relevance to the alzheimers animal model.
AB  - BACKGROUND: Alzheimers disease (AD) is a devastative neurodegenerative disorder.
      Lack of substantial animal model that can unravel molecular underpinnings has
      been a major lacuna which limited the understanding of the etiology of the
      disease in turn limiting the employment of potential therapeutic strategies to
      combat the disease for a few decades. Our studies for the first time provided
      substantial animal model and tattered the etiology of the disease at a molecular
      level. METHODS: In this study DNA was isolated from Hippocampus (H), Midbrain (M)
      and Frontal Cortex (Fc) of control and aluminium maltolate (Al-M) treated aged
      New Zealand rabbit brain. DNA damage has been studied using Agarose gel
      electrophoresis, Ethidium Bromide (EtBr) binding and Melting temperature
      techniques. RESULTS: Al-M treated aged New Zealand rabbit's H and M showed higher
      DNA damage compared to corresponding controls, where as Fc showed mild DNA damage
      compared to corresponding controls. CONCLUSIONS: This study tangibly provides
      substantial molecular level understanding of the disease in turn providing an
      adequate platform to streamline potential therapeutic strategies. KEYWORDS:
      Alzheimer's disease; Aluminium maltolate; Animal model; DNA damage.

PMID- 22461872
TI  - The unstimulated salivary flow rate in a jordanian healthy adult population.
AB  - BACKGROUND: Early diagnosis of xerostomia is very important for oral health. The
      purpose of this study was to determine the unstimulated whole salivary flow rates
      (UWSFR) in a Jordanian Arab population aged 15 years and older. The effect of
      age, gender, height, weight, body mass index (BMI), smoking, alcohol consumption,
      and dental conditions, on UWSFR was also investigated. METHODS: The study was
      conducted on 244 subjects, 110 males and 134 females, with an average age of 33
      +/- 15.5 years. They were healthy, unmedicated, and with no history of dry mouth.
      Unstimulated whole saliva was collected during five minutes, and UWSFRs (ml/min)
      were determined. Data were analyzed by univariate analysis and multivariate
      regression analysis. RESULTS: The mean UWSFR was 0.46 +/- 0.25 ml/min (range:
      0.10-1.6 ml/min). Eighteen patients (7.4%) had UWSFR between < 0.20 ml/min. In
      univariate analysis, UWSFR was significantly affected by age, BMI, number of
      missing and restored teeth, and DMFT score. Regression analysis revealed that
      only age and number of missing teeth were of significance in explaining the
      variability of the UWSFR. CONCLUSIONS: We established basic standard values of
      UWSFR to be used in the evaluation of Jordanian patients with complaints of
      xerostomia and to be compared to data reported in other studies. UWSFR 0.1 ml/min
      could be considered the cut-off value that distinguishes normal from abnormal
      salivary function in this healthy unmedicated population. KEYWORDS: Whole saliva
      flow rate; Unstimulated; Jordan.

PMID- 22461873
TI  - Management of giant ventral hernia by polypropylene mesh and host tissue barrier:
      trial of simplification.
AB  - BACKGROUND: Surgical management of giant ventral hernias is a surgical challenge
      due to limited abdominal cavity. This study evaluates management of giant ventral
      hernias using polypropylene mesh and host tissue barrier after suitable
      preoperative preparation. METHODS: In the period from January 2005 and January
      2007, 35 patients with giant ventral hernias underwent hernia repair. After
      careful preoperative preparation, repair was done using polypropylene mesh. The
      mesh was separated from the viscera by a small part of the hernia sac and the
      greater omentum. RESULTS: The average age of the patients was 52. Twenty patients
      had post-operative incisional and 15 had para-umbilical hernias. The mean hernia
      defect size was 16.8 cm. Mean body mass index was 33. Follow up ranged from 18-36
      months. No patient required ventilation after operation. Recurrent seroma, which
      responded to repeated aspiration, was experienced in 4 patients. Minor wound
      infection was observed in 5 patients. Small hernia recurrence occurred in one
      patient. CONCLUSION: The use of polypropylene and host tissue barrier after
      suitable preoperative preparation is relatively simple, safe, and reliable
      surgical solution to the problem of giant ventral hernia. KEYWORDS: Hernia
      repair; Giant ventral hernia; Polypropylene mesh.

PMID- 22461874
TI  - A Case of Dropped Head plus Syndrome.
AB  - A patient developed neck extensor weakness along with symmetrical, mild proximal
      extremity weakness. Electrodiagnostic findings were minimal. Subsequently muscle
      biopsy was undertaken which showed myopathic changes as well as rimmed vacuoles.
      This case highlights the discussion of histopatholgical findings seen in neck
      extensor weakness when it occurs in isolation as well as when it is associated
      with weakness in other distribution. KEYWORDS: Neck extensor weakness; Rimmed
      vacuoles; Myopathy.

PMID- 22461875
TI  - Malignant schwannoma of anterior abdominal wall: report of a case.
AB  - Malignant schwannoma of the anterior abdominal wall nerves is extremely rare.
      Malignant peripheral nerve sheath tumors (MPNST) represent approximately 10% of
      all soft tissue sarcomas and it is found in 4% of patients with neurofibromatosis
      1. We present a case of malignant schwannoma in a 28-year-old female patient with
      neurofibromatosis 1. She presented with a painful mass in the right upper
      quadrant of her abdomen. The tumor location was in the abdominal wall in
      explorative laparatomy and malignant schwannoma was diagnosed in pathologic
      assessment. The tumor recurred in 3 months and computed tomography showed two
      masses in the right side of abdominopelvic cavity. Thereafter, second complete
      surgical resection was performed and pathologic finding was the same. In spite of
      administering chemotherapy after second surgery,the tumor recurred and magnetic
      resonance imaging finding showed a huge heterogeneously enhancing mass with
      adhesion to the inner side of the abdominal wall. The patient died because of
      acute respiratory failure due to multiple bilateral pulmonary metastases. Tumor
      location and rapid recurrence was unique in our patient. KEYWORDS: Malignant
      peripheral nerve sheath tumor; Malignant schwannoma; Abdominal wall.

PMID- 22461876
TI  - A rare case of primary mucinous cystadenoma of spleen.
AB  - Mucinous cystadenomas are relatively uncommon benign cystic tumors. Most of them
      are found in the ovary, pancreas, and appendix. Primary mucinous cystadenoma of
      spleen is extremely rare and only countable cases have been recorded. These are
      assumed to arise from heterotopic pancreatic tissue or invaginated spleenic
      capsular mesothelium. We present a rare case of primary mucinous cystadenoma of
      spleen without pancreatic tissue in it. Exact tissue of origin could not be
      determined. KEYWORDS: Cystadenoma; Splenic cyst; Pseudomyxoma peritonei.

PMID- 22461877
TI  - Doppler echocardiographic diagnosis of a rare pentalogy of fallot having penta
      cardiac anomalies: a case report.
AB  - An infant, showing peripheral cyanosis, was born after lower abdominal peripheral
      caesarian section of the pregnant women having TORCH positive test with the
      infection of Toxoplasma gondiiand Cytomegalovirus. She had three abortions prior
      to this pregnancy. Doppler echocardiography of the baby showed profound
      intracardiac defects. After birth, echocardiography was carried out for diagnosis
      of associated cardiac anomalies. Doppler echocardiography showed pentalogy of
      Fallot, and the present case represents the Pentalogy of Fallot having pulmonary
      atresia. The baby's heart anomalies were ASD (Atrial Septal Defect - 6 mm RT to
      LT Shunt), VSD (Ventricular Septal Defect - bidirectional shunt), PDA (Patent
      Ductus Arteriosus - filling both the pulmonary arteries), and Overriding of Aorta
      with pulmonary atresia. In conclusion, whenever the diagnosis pentalogy of fallot
      is suspected, a multidisciplinary approach is essential. KEYWORDS: Pentalogy of
      fallot; Overriding Aorta; Ventricular Septal Defect; Atrial Septal Defect;
      Pulmonary Atresia; Doppler Echocardiography.

PMID- 22461878
TI  - Kikuchi-fujimoto disease: diagnostic dilemma and the role of
      immunohistochemistry.
AB  - Kikuchi-Fujimoto (KD) disease is the rare differential diagnoses of chronic
      cervical lymphadenopathy of unknown etiology. The findings of histopathology may
      be overlapping, in such condition immunohistochemistry has a definite role to
      play. Since Tubercular lymphadenopathy is the commonest cause for chronic
      cervical lymphadenopathy in developing and tropical country like India.
      Occasionally it is misdiagnosed, ignoring the other rare condition like KD if
      immunohistochemistry is not taken into consideration to differentiate. As a
      result the morbidity increases and cost of antitubercular treatment (ATT) in
      wrong diagnosed case is enormous. We report a similar case of misdiagnoses, non
      responsive to ATT, finally diagnosed as a case of Kikuchi-Fujimoto disease, did
      well after recommended treatment. KEYWORDS: Necrotizing lymphadenitis; Chronic
      cervical lymphadenitis; Immunohistochemistry.

PMID- 22461879
TI  - Varicella zoster infection: a rare cause of abdominal pain mimicking acute
      abdomen.
AB  - Varicella zoster is an acute viral infection that results from reactivation of a
      latent varicella zoster virus. It usually occurs in adult population and immune
      compromised patients. It rarely occurs in healthy children. Here we present a 14
      years old male with varicella zoster that had abdominal pain mimicking acute
      abdomen to alert others who are consulted for the differentiation of acute
      abdomen and others who may be consulted for pain management. KEYWORDS: Varicella
      zoster; Abdominal pain.

PMID- 22461883
TI  - Use of a deformable atlas to identify cryptic critical structures in the
      treatment of glioblastoma multiforme.
AB  - Dose constraints for traditional neural critical structures (e.g. optic chiasm,
      brain stem) are a standard component of planning radiation therapy to the central
      nervous system. Increasingly, investigators are becoming interested in accounting
      for the dose delivered to other non-target neural structures (e.g. hippocampi),
      which are not easily identified on axial imaging. In this pilot study, a
      commercially available digital atlas was used to identify cryptic neural
      structures (hippocampus, optic radiations, and visual cortices) in 6 patients who
      received intensity modulated radiation therapy (IMRT) as part of multimodal
      management of glioblastoma multiforme (GBM). The patient's original IMRT plans
      were re-optimized, with avoidance parameters for the newly identified critical
      structures. Re-optimization was able to reduce both mean and maximum dose to the
      volumes of interest, with a more pronounced effect for contralateral structures.
      Mean dose was reduced by 11% and 3% to contralateral and ipsilateral structures,
      respectively, with comparable reduction in maximum dose of 10% and 2%,
      respectively. Importantly, target coverage was not compromised, with an average
      change in coverage of 0.2%. Overall, our results demonstrate the feasibility of
      incorporating tools for cryptic critical structure identification into the
      treatment planning process for GBM.

PMID- 22461884
TI  - Hyccin, the molecule mutated in the leukodystrophy hypomyelination and congenital
      cataract (HCC), is a neuronal protein.
AB  - "Hypomyelination and Congenital Cataract", HCC (MIM #610532), is an autosomal
      recessive disorder characterized by congenital cataract and diffuse cerebral and
      peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein
      whose biological role has not been clarified yet. Since the identification of the
      cell types expressing a protein of unknown function can contribute to define the
      physiological context in which the molecule is explicating its function, we
      analyzed the pattern of Hyccin expression in the central and peripheral nervous
      system (CNS and PNS). Using heterozygous mice expressing the b-galactosidase
      (LacZ) gene under control of the Hyccin gene regulatory elements, we show that
      the gene is primarily expressed in neuronal cells. Indeed, Hyccin-LacZ signal was
      identified in CA1 hippocampal pyramidal neurons, olfactory bulb, and cortical
      pyramidal neurons, while it did not colocalize with oligodendroglial or
      astrocytic markers. In the PNS, Hyccin was detectable only in axons isolated from
      newborn mice. In the brain, Hyccin transcript levels were higher in early
      postnatal development (postnatal days 2 and 10) and then declined in adult mice.
      In a model of active myelinogenesis, organotypic cultures of rat Schwann cells
      (SC)/Dorsal Root Ganglion (DRG) sensory neurons, Hyccin was detected along the
      neurites, while it was absent from SC. Intriguingly, the abundance of the
      molecule was upregulated at postnatal days 10 and 15, in the initial steps of
      myelinogenesis and then declined at 30 days when the process is complete. As
      Hyccin is primarily expressed in neurons and its mutation leads to
      hypomyelination in human patients, we suggest that the protein is involved in
      neuron-to-glia signalling to initiate or maintain myelination.

PMID- 22461885
TI  - A unified multitask architecture for predicting local protein properties.
AB  - A variety of functionally important protein properties, such as secondary
      structure, transmembrane topology and solvent accessibility, can be encoded as a
      labeling of amino acids. Indeed, the prediction of such properties from the
      primary amino acid sequence is one of the core projects of computational biology.
      Accordingly, a panoply of approaches have been developed for predicting such
      properties; however, most such approaches focus on solving a single task at a
      time. Motivated by recent, successful work in natural language processing, we
      propose to use multitask learning to train a single, joint model that exploits
      the dependencies among these various labeling tasks. We describe a deep neural
      network architecture that, given a protein sequence, outputs a host of predicted
      local properties, including secondary structure, solvent accessibility,
      transmembrane topology, signal peptides and DNA-binding residues. The network is
      trained jointly on all these tasks in a supervised fashion, augmented with a
      novel form of semi-supervised learning in which the model is trained to
      distinguish between local patterns from natural and synthetic protein sequences.
      The task-independent architecture of the network obviates the need for task
      specific feature engineering. We demonstrate that, for all of the tasks that we
      considered, our approach leads to statistically significant improvements in
      performance, relative to a single task neural network approach, and that the
      resulting model achieves state-of-the-art performance.

PMID- 22461886
TI  - The role of LDH serum levels in predicting global outcome in HCC patients
      undergoing TACE: implications for clinical management.
AB  - In many tumor types serum lactate dehydrogenase (LDH) levels is an indirect
      marker of tumor hypoxia, neo-angiogenesis and worse prognosis. However data about
      hepatocellular carcinoma (HCC) are lacking in the clinical setting of patients
      undergoing transarterial-chemoembolization (TACE) in whom hypoxia and neo
      angiogenesis may represent a molecular key to treatment failure. Aim of our
      analysis was to evaluate the role of LDH pre-treatment levels in determining
      clinical outcome for patients with HCC receiving TACE. One hundred and fourteen
      patients were available for our analysis. For all patients LDH values were
      collected within one month before the procedure. We divided our patients into two
      groups, according to LDH serum concentration registered before TACE (first:
      LDH<=450 U/l 84 patients; second: LDH>450 U/l 30 patients). Patients were
      classified according to the variation in LDH serum levels pre- and post-treatment
      (increased: 62 patients vs. decreased 52 patients). No statistically significant
      differences were found between the groups for all clinical characteristics
      analyzed (gender, median age, performance status ECOG, staging systems). In
      patients with LDH values below 450 U/l median time to progression (TTP) was 16.3
      months, whereas it was of 10.1 months in patients above the cut-off (p = 0.0085).
      Accordingly median overall survival (OS) was 22.4 months and 11.7 months (p =
      0.0049). In patients with decreased LDH values after treatment median TTP was
      12.4 months, and median OS was 22.1 months, whereas TTP was 9.1 months and OS was
      9.5 in patients with increased LDH levels (TTP: p = 0.0087; OS: p<0.0001). In our
      experience, LDH seemed able to predict clinical outcome for HCC patients
      undergoing TACE. Given the correlation between LDH levels and tumor angiogenesis
      we can speculate that patients with high LDH pretreatment levels may be optimal
      candidates for clinical trial exploring a multimodality treatment approach with
      TACE and anti-VEGF inhibitors in order to improve TTP and OS.

PMID- 22461887
TI  - Subject positioning in the BOD POD(r) only marginally affects measurement of body
      volume and estimation of percent body fat in young adult men.
AB  - INTRODUCTION: The aim of the study was to evaluate whether subject positioning
      would affect the measurement of raw body volume, thoracic gas volume, corrected
      body volume and the resulting percent body fat as assessed by air displacement
      plethysmography (ADP). METHODS: Twenty-five young adult men (20.7+/-1.1 y, BMI =
      22.5+/-1.4 kg/m(2)) were measured using the BOD POD(r) system using a measured
      thoracic gas volume sitting in a 'forward bent' position and sitting up in a
      straight position in random order. RESULTS: Raw body volume was 58+/-124 ml
      (p<0.05) higher in the 'straight' position compared to the 'bent' position. The
      mean difference in measured thoracic gas volume (bent-straight = -71+/-211 ml)
      was not statistically significant. Corrected body volume and percent body fat in
      the bent position consequently were on average 86+/-122 ml (p<0.05) and 0.5+/
      0.7% (p<0.05) lower than in the straight position respectively. CONCLUSION:
      Although the differences reached statistical significance, absolute differences
      are rather small. Subject positioning should be viewed as a factor that may
      contribute to between-test variability and hence contribute to (in)precision in
      detecting small individual changes in body composition, rather than a potential
      source of systematic bias. It therefore may be advisable to pay attention to
      standardizing subject positioning when tracking small changes in PF are of
      interest. The cause of the differences is shown not to be related to changes in
      the volume of isothermal air in the lungs. It is hypothesized and calculated that
      the observed direction and magnitude of these differences may arise from the
      surface area artifact which does not take into account that a subject in the bent
      position exposes more skin to the air in the device therefore potentially
      creating a larger underestimation of the actual body volume due to the isothermal
      effect of air close to the skin.

PMID- 22461888
TI  - Interaction analysis between HLA-DRB1 shared epitope alleles and MHC class II
      transactivator CIITA gene with regard to risk of rheumatoid arthritis.
AB  - HLA-DRB1 shared epitope (SE) alleles are the strongest genetic determinants for
      autoantibody positive rheumatoid arthritis (RA). One of the key regulators in
      expression of HLA class II receptors is MHC class II transactivator (CIITA). A
      variant of the CIITA gene has been found to associate with inflammatory
      diseases.We wanted to explore whether the risk variant rs3087456 in the CIITA
      gene interacts with the HLA-DRB1 SE alleles regarding the risk of developing RA.
      We tested this hypothesis in a case-control study with 11767 individuals from
      four European Caucasian populations (6649 RA cases and 5118 controls).We found no
      significant additive interaction for risk alleles among Swedish Caucasians with
      RA (n = 3869, attributable proportion due to interaction (AP) = 0.2, 95%CI: -0.2
      0.5) or when stratifying for anti-citrullinated protein antibodies (ACPA)
      presence (ACPA positive disease: n = 2945, AP = 0.3, 95%CI: -0.05-0.6, ACPA
      negative: n = 2268, AP = -0.2, 95%CI: -1.0-0.6). We further found no significant
      interaction between the main subgroups of SE alleles (DRB1*01, DRB1*04 or
      DRB1*10) and CIITA. Similar analysis of three independent RA cohorts from
      British, Dutch and Norwegian populations also indicated an absence of significant
      interaction between genetic variants in CIITA and SE alleles with regard to RA
      risk.Our data suggest that risk from the CIITA locus is independent of the major
      risk for RA from HLA-DRB1 SE alleles, given that no significant interaction
      between rs3087456 and SE alleles was observed. Since a biological link between
      products of these genes is evident, the genetic contribution from CIITA and class
      II antigens in the autoimmune process may involve additional unidentified
      factors.

PMID- 22461889
TI  - Detecting regulatory mechanisms in endocrine time series measurements.
AB  - The regulatory mechanisms underlying pulsatile secretion are complex, especially
      as it is partly controlled by other hormones and the combined action of multiple
      agents. Regulatory relations between hormones are not directly observable but may
      be deduced from time series measurements of plasma hormone concentrations.
      Variation in plasma hormone levels are the resultant of secretion and clearance
      from the circulation. A strategy is proposed to extract inhibition, activation,
      thresholds and circadian synchronicity from concentration data, using particular
      association methods. Time delayed associations between hormone concentrations
      and/or extracted secretion pulse profiles reveal the information on regulatory
      mechanisms. The above mentioned regulatory mechanisms are illustrated with
      simulated data. Additionally, data from a lean cohort of healthy control subjects
      is used to illustrate activation (ACTH and cortisol) and circadian synchronicity
      (ACTH and TSH) in real data. The simulation and the real data both consist of 145
      equidistant samples per individual, matching a 24-hr time span with 10 minute
      intervals. The results of the simulation and the real data are in concordance.

PMID- 22461890
TI  - Engulfing astrocytes protect neurons from contact-induced apoptosis following
      injury.
AB  - Clearing of dead cells is a fundamental process to limit tissue damage following
      brain injury. Engulfment has classically been believed to be performed by
      professional phagocytes, but recent data show that non-professional phagocytes
      are highly involved in the removal of cell corpses in various situations. The
      role of astrocytes in cell clearance following trauma has however not been
      studied in detail. We have found that astrocytes actively collect and engulf
      whole dead cells in an in vitro model of brain injury and thereby protect healthy
      neurons from bystander cell death. Time-lapse experiments showed that migrating
      neurons that come in contact with free-floating cell corpses induced apoptosis,
      while neurons that migrate through groups of dead cells, garnered by astrocytes,
      remain unaffected. Furthermore, apoptotic cells are present within astrocytes in
      the mouse brain following traumatic brain injury (TBI), indicating a possible
      role for astrocytes in engulfment of apoptotic cells in vivo. qRT-PCR analysis
      showed that members of both ced pathways and Megf8 are expressed in the cell
      culture, indicating their possible involvement in astrocytic engulfment.
      Moreover, addition of dead cells had a positive effect on the protein expression
      of MEGF10, an ortholog to CED1, known to initiate phagocytosis by binding to
      phosphatidylserine. Although cultured astrocytes have an immense capacity for
      engulfment, seemingly without adverse effects, the ingested material is stored
      rather than degraded. This finding might explain the multinuclear astrocytes that
      are found at the lesion site in patients with various brain disorders.

PMID- 22461891
TI  - CIP2A promotes proliferation of spermatogonial progenitor cells and
      spermatogenesis in mice.
AB  - Protein phosphatase 2A (PP2A) is a critical regulator of protein serine/threonine
      phosphorylation. However, the physiological and developmental roles of different
      PP2A complexes are very poorly understood. Here, we show that a newly
      characterized PP2A inhibitory protein CIP2A is co-expressed with ki-67 and with
      self-renewal protein PLZF in the spermatogonial progenitor cell (SPC) population
      in the testis. CIP2A and PLZF expression was shown also to correlate Ki-67
      expression in human testicular spermatogonia. Functionally, CIP2A mutant mouse
      testes exhibited smaller number of PLZF-positive SPCs and reduced sperm counts.
      Moreover, seminiferous tubuli cells isolated from CIP2A mutant mice showed
      reduced expression of Plzf and other renewal genes Oct-4 and Nanog at mRNA level.
      However, PLZF-deficient testes did not show altered CIP2A expression.
      Importantly, spermatogonia-specific restoration of CIP2A expression rescued PLZF
      expression and sperm production defects observed in CIP2A mutant mice. Taken
      together, these results reveal first physiological function for an emerging human
      oncoprotein CIP2A, and provide insights into maintenance of PLZF-positive
      progenitors. Moreover, demonstration that CIP2A expression can be systematically
      inhibited without severe consequences to normal mouse development and viability
      may have clinical relevance regarding targeting of oncogenic CIP2A for future
      cancer therapies.

PMID- 22461892
TI  - How does information processing speed relate to the attentional blink?
AB  - BACKGROUND: When observers are asked to identify two targets in rapid sequence,
      they often suffer profound performance deficits for the second target, even when
      the spatial location of the targets is known. This attentional blink (AB) is
      usually attributed to the time required to process a previous target, implying
      that a link should exist between individual differences in information processing
      speed and the AB. METHODOLOGY/PRINCIPAL FINDINGS: The present work investigated
      this question by examining the relationship between a rapid automatized naming
      task typically used to assess information-processing speed and the magnitude of
      the AB. The results indicated that faster processing actually resulted in a
      greater AB, but only when targets were presented amongst high similarity
      distractors. When target-distractor similarity was minimal, processing speed was
      unrelated to the AB. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that
      information-processing speed is unrelated to target processing efficiency per se,
      but rather to individual differences in observers' ability to suppress
      distractors. This is consistent with evidence that individuals who are able to
      avoid distraction are more efficient at deploying temporal attention, but argues
      against a direct link between general processing speed and efficient information
      selection.

PMID- 22461893
TI  - Timing of first exposure to maternal depression and adolescent emotional disorder
      in a national Canadian cohort.
AB  - OBJECTIVE: Correlations have been reported between behavioral and cognitive
      outcomes in adolescence and exposure to maternal depression during the first
      postpartum year, but the effects of timing of maternal depression during
      subsequent exposure periods have rarely been controlled for. This study aims to
      methodically investigate the importance of timing of initial exposure to maternal
      depression with respect to adolescent mental health outcomes. METHODS: This study
      used data on 937 children from the National Longitudinal Study of Children and
      Youth (NLSCY), a nationally-representative longitudinal survey established in
      1994 by Statistics Canada. Ordinal logistic regression was used to confirm
      associations between adolescent emotional disorder (at 12-13 years) and initial
      exposure to maternal depression during 2-year intervals from birth to
      adolescence. Following their initial exposure to maternal depression, children
      were dropped from subsequent cycles. Stressful life events, chronic health
      conditions, maternal alcohol use, maternal marital status, gender, and SES were
      included as covariates. RESULTS: The results indicated that adolescents who were
      initially exposed to maternal depression between the ages of 2-3 years and 4-5
      years had a two-fold increase in odds of emotional disorder. No increase in odds
      was observed in those initially exposed during the first postpartum year or later
      in childhood. CONCLUSIONS: The results demonstrate that a sensitive period of
      initial exposure to maternal depression may occur between the ages of 2 and 5,
      and not during the first year of life indicated by previous research. These
      findings are congruent with the literature on emotional and behavioral
      development in early childhood.

PMID- 22461894
TI  - Integrating intracellular dynamics using CompuCell3D and Bionetsolver:
      applications to multiscale modelling of cancer cell growth and invasion.
AB  - In this paper we present a multiscale, individual-based simulation environment
      that integrates CompuCell3D for lattice-based modelling on the cellular level and
      Bionetsolver for intracellular modelling. CompuCell3D or CC3D provides an
      implementation of the lattice-based Cellular Potts Model or CPM (also known as
      the Glazier-Graner-Hogeweg or GGH model) and a Monte Carlo method based on the
      metropolis algorithm for system evolution. The integration of CC3D for cellular
      systems with Bionetsolver for subcellular systems enables us to develop a
      multiscale mathematical model and to study the evolution of cell behaviour due to
      the dynamics inside of the cells, capturing aspects of cell behaviour and
      interaction that is not possible using continuum approaches. We then apply this
      multiscale modelling technique to a model of cancer growth and invasion, based on
      a previously published model of Ramis-Conde et al. (2008) where individual cell
      behaviour is driven by a molecular network describing the dynamics of E-cadherin
      and beta-catenin. In this model, which we refer to as the centre-based model, an
      alternative individual-based modelling technique was used, namely, a lattice-free
      approach. In many respects, the GGH or CPM methodology and the approach of the
      centre-based model have the same overall goal, that is to mimic behaviours and
      interactions of biological cells. Although the mathematical foundations and
      computational implementations of the two approaches are very different, the
      results of the presented simulations are compatible with each other, suggesting
      that by using individual-based approaches we can formulate a natural way of
      describing complex multi-cell, multiscale models. The ability to easily reproduce
      results of one modelling approach using an alternative approach is also essential
      from a model cross-validation standpoint and also helps to identify any modelling
      artefacts specific to a given computational approach.

PMID- 22461895
TI  - PTRF/cavin-1 and MIF proteins are identified as non-small cell lung cancer
      biomarkers by label-free proteomics.
AB  - With the completion of the human genome sequence, biomedical sciences have
      entered in the "omics" era, mainly due to high-throughput genomics techniques and
      the recent application of mass spectrometry to proteomics analyses. However,
      there is still a time lag between these technological advances and their
      application in the clinical setting. Our work is designed to build bridges
      between high-performance proteomics and clinical routine. Protein extracts were
      obtained from fresh frozen normal lung and non-small cell lung cancer samples. We
      applied a phosphopeptide enrichment followed by LC-MS/MS. Subsequent label-free
      quantification and bioinformatics analyses were performed. We assessed protein
      patterns on these samples, showing dozens of differential markers between normal
      and tumor tissue. Gene ontology and interactome analyses identified signaling
      pathways altered on tumor tissue. We have identified two proteins, PTRF/cavin-1
      and MIF, which are differentially expressed between normal lung and non-small
      cell lung cancer. These potential biomarkers were validated using western blot
      and immunohistochemistry. The application of discovery-based proteomics analyses
      in clinical samples allowed us to identify new potential biomarkers and
      therapeutic targets in non-small cell lung cancer.

PMID- 22461896
TI  - Dynamic regulation of Tgf-B signaling by Tif1gamma: a computational approach.
AB  - TIF1gamma (Transcriptional Intermediary Factor 1 gamma) has been implicated in
      Smad-dependent signaling by Transforming Growth Factor beta (TGF-beta).
      Paradoxically, TIF1gamma functions both as a transcriptional repressor or as an
      alternative transcription factor that promotes TGF-beta signaling. Using ordinary
      differential-equation models, we have investigated the effect of TIF1gamma on the
      dynamics of TGF-beta signaling. An integrative model that includes the formation
      of transient TIF1gamma-Smad2-Smad4 ternary complexes is the only one that can
      account for TGF-beta signaling compatible with the different observations
      reported for TIF1gamma. In addition, our model predicts that varying
      TIF1gamma/Smad4 ratios play a critical role in the modulation of the
      transcriptional signal induced by TGF-beta, especially for short stimulation
      times that mediate higher threshold responses. Chromatin immunoprecipitation
      analyses and quantification of the expression of TGF-beta target genes as a
      function TIF1gamma/Smad4 ratios fully validate this hypothesis. Our integrative
      model, which successfully unifies the seemingly opposite roles of TIF1gamma, also
      reveals how changing TIF1gamma/Smad4 ratios affect the cellular response to
      stimulation by TGF-beta, accounting for a highly graded determination of cell
      fate.

PMID- 22461897
TI  - Neurocognitive dysfunction in systemic lupus erythematosus: association with
      antiphospholipid antibodies, disease activity and chronic damage.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is characterized by frequent
      neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed
      at assessing CI in a cohort of Italian SLE patients by using a wide range of
      neurocognitive tests specifically designed to evaluate the fronto-subcortical
      dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated
      with serum autoantibodies, disease activity and chronic damage. METHODS: Fifty
      eight consecutive patients were enrolled. Study protocol included data
      collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti
      beta(2)-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5
      antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and
      chronic damage. Patients were administered a test battery specifically designed
      to detect fronto-subcortical dysfunction across five domains: memory, attention,
      abstract reasoning, executive function and visuospatial function. For each
      patient, the raw scores from each test were compared with published norms, then
      transformed into Z scores (deviation from normal mean), and finally summed in the
      Global Cognitive Dysfunction score (GCDs). RESULTS: Nineteen percent of patients
      had mild GCDs impairment (GCDs 2-3), 7% moderate (GCDs 4-5) and 5% severe
      (GCDs>=6). The visuospatial domain was the most compromised (MDZs = -0.89+/
      1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain
      impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional
      and executive domains; SLICC correlated with GCDs, and with visuospatial and
      attentional domains impairment. CONCLUSIONS: Anti-phospholipids, disease
      activity, and chronic damage are associated with cognitive dysfunction in SLE.
      The use of a wide spectrum of tests allowed for a better selection of the
      relevant factors involved in SLE cognitive dysfunction, and standardized
      neuropsychological testing methods should be used for routine assessment of SLE
      patients.

PMID- 22461898
TI  - A 3' UTR SNP in COL18A1 is associated with susceptibility to HBV related
      hepatocellular carcinoma in Chinese: three independent case-control studies.
AB  - BACKGROUND: Accumulated evidences indicate that single nucleotide polymorphisms
      (SNP) in angiogenesis and tumorigenesis related genes are associated with risk of
      Hepatocellular carcinoma (HCC). COL18A1 encodes the precursor of endostatin,
      which is a broad-spectrum angiogenesis inhibitor, and we speculate that SNPs in
      COL18A1 may be associated with susceptibility to HCC. METHODS AND FINDINGS: We
      carried out a 2-stage association study in 3 independent case-control groups in a
      total of 1067 chronic hepatitis B (CHB) patients and 808 hepatitis B virus (HBV)
      related HCC patients in Han Chinese. Four SNPs which can represent all potential
      functional SNPs with MAF>0.1 recorded in HapMap database were genotyped using
      TaqMan methods. Levels of total COL18A1 mRNA were also examined using
      quantitative real-time RT-PCR. We found that rs7499 located in 3'-UTR to be
      strongly associated with HBV related HCC (P(combined) = 0.0000005, OR = 0.72,
      95%CI = 0.63-0.82). COL18A1 mRNA expression was significantly decreased as the
      disease progressed (P = 0.000026). CONCLUSION: These findings indicate that
      COL18A1 rs7499 may contribute to the risk of HCC in Han Chinese.

PMID- 22461899
TI  - The rph2 gene is responsible for high level resistance to phosphine in
      independent field strains of Rhyzopertha dominica.
AB  - The lesser grain borer Rhyzopertha dominica (F.) is one of the most destructive
      insect pests of stored grain. This pest has been controlled successfully by
      fumigation with phosphine for the last several decades, though strong resistance
      to phosphine in many countries has raised concern about the long term usefulness
      of this control method. Previous genetic analysis of strongly resistant (SR) R.
      dominica from three widely geographically dispersed regions of Australia,
      Queensland (SR(QLD)), New South Wales (SR(NSW)) and South Australia (SR(SA)),
      revealed a resistance allele in the rph1 gene in all three strains. The present
      study confirms that the rph1 gene contributes to resistance in a fourth strongly
      resistant strain, SR2(QLD), also from Queensland. The previously described rph2
      gene, which interacts synergistically with rph1 gene, confers strong resistance
      on SR(QLD) and SR(NSW). We now provide strong circumstantial evidence that weak
      alleles of rph2, together with rph1, contribute to the strong resistance
      phenotypes of SR(SA) and SR2(QLD). To test the notion that rph1 and rph2 are
      solely responsible for the strong resistance phenotype of all resistant R.
      dominica, we created a strain derived by hybridising the four strongly resistant
      lines. Following repeated selection for survival at extreme rates of phosphine
      exposure, we found only slightly enhanced resistance. This suggests that a single
      sequence of genetic changes was responsible for the development of resistance in
      these insects.

PMID- 22461900
TI  - Can the tumor deposits be counted as metastatic lymph nodes in the UICC TNM
      staging system for colorectal cancer?
AB  - OBJECTIVE: The 7th edition of AJCC staging manual implicitly states that only T1
      and T2 lesions that lack regional lymph node metastasis but have tumor deposit(s)
      will be classified in addition as N1c, though it is not consistent in that pN1c
      is also an option for pT3/T4a tumors in the staging table. Nevertheless, in this
      TNM classification, how to classify tumor deposits (TDs) in colorectal cancer
      patients with lymph node metastasis (LNM) and TDs simultaneously is still not
      clear. The aim of this study is to investigate the possibility of counting TDs as
      metastatic lymph nodes in TNM classification and to identify its prognostic value
      for colorectal cancer patients. METHODS AND RESULTS: In this retrospective study,
      513 cases of colorectal cancer with LNM were reviewed. We proposed a novel pN
      (npN) category in which TDs were counted as metastatic lymph nodes in the TNM
      classification. Cancer-specific survival according to the npN or pN category was
      analyzed using Kaplan-Meier survival curves. Univariate and multivariate analyses
      were performed to identify significant prognostic factors. Harrell's C statistic
      was used to test the predictive capacity of the prognostic models. The results
      revealed that the TD was a significant prognostic factor in colorectal cancer.
      Univariate and multivariate analyses uniformly indicated that the npN category
      was significantly correlated with prognosis. The results of Harrell's C
      statistical analysis demonstrated that the npN category exhibited a superior
      predictive capacity compared to the pN category of the 7th edition TNM
      classification. Moreover, we also found no significant prognostic differences in
      patients with or without TD in the same npN categories. CONCLUSIONS: The counting
      of TDs as metastatic lymph nodes in the TNM classification system is potentially
      superior to the classification in the 7th edition of the TNM staging system to
      assess prognosis and survival for colorectal cancer patients.

PMID- 22461901
TI  - Bmp7 regulates the survival, proliferation, and neurogenic properties of neural
      progenitor cells during corticogenesis in the mouse.
AB  - Bone morphogenetic proteins (BMPs) are considered important regulators of neural
      development. However, results mainly from a wide set of in vitro gain-of-function
      experiments are conflicting since these show that BMPs can act either as
      inhibitors or promoters of neurogenesis. Here, we report a specific and non
      redundant role for BMP7 in cortical neurogenesis in vivo using knockout mice.
      Bmp7 is produced in regions adjacent to the developing cortex; the hem, meninges,
      and choroid plexus, and can be detected in the cerebrospinal fluid. Bmp7 deletion
      results in reduced cortical thickening, impaired neurogenesis, and loss of radial
      glia attachment to the meninges. Subsequent in vitro analyses of E14.5 cortical
      cells revealed that lack of Bmp7 affects neural progenitor cells, evidenced by
      their reduced proliferation, survival and self-renewal capacity. Addition of BMP7
      was able to rescue these proliferation and survival defects. In addition, at the
      developmental stage E14.5 Bmp7 was also required to maintain Ngn2 expression in
      the subventricular zone. These data demonstrate a novel role for Bmp7 in the
      embryonic mouse cortex: Bmp7 nurtures radial glia cells and regulates fundamental
      properties of neural progenitor cells that subsequently affect Ngn2-dependent
      neurogenesis.

PMID- 22461902
TI  - The significance of hair for face recognition.
AB  - Hair is a feature of the head that frequently changes in different situations.
      For this reason much research in the area of face perception has employed stimuli
      without hair. To investigate the effect of the presence of hair we used faces
      with and without hair in a recognition task. Participants took part in trials in
      which the state of the hair either remained consistent (Same) or switched between
      learning and test (Switch). It was found that in the Same trials performance did
      not differ for stimuli presented with and without hair. This implies that there
      is sufficient information in the internal features of the face for optimal
      performance in this task. It was also found that performance in the Switch trials
      was substantially lower than in the Same trials. This drop in accuracy when the
      stimuli were switched suggests that faces are represented in a holistic manner
      and that manipulation of the hair causes disruption to this, with implications
      for the interpretation of some previous studies.

PMID- 22461903
TI  - Age affects quantity but not quality of antibody responses after vaccination with
      an inactivated flavivirus vaccine against tick-borne encephalitis.
AB  - The impairment of immune functions in the elderly (immunosenescence) results in
      post-vaccination antibody titers that are significantly lower than in young
      individuals. It is, however, a controversial question whether also the quality of
      antibodies declines with age. In this study, we have therefore investigated the
      age-dependence of functional characteristics of antibody responses induced by
      vaccination with an inactivated flavivirus vaccine against tick-borne
      encephalitis (TBE). For this purpose, we quantified TBE virus-specific IgG and
      neutralizing antibody titers in post-vaccination sera from groups of young and
      elderly healthy adults and determined antibody avidities and NT/ELISA titer
      ratios (functional activity). In contrast to the quantitative impairment of
      antibody production in the elderly, we found no age-related differences in the
      avidity and functional activity of antibodies induced by vaccination, which also
      appeared to be independent of the age at primary immunization. There was no
      correlation between antibody avidity and NT/ELISA ratios suggesting that
      additional factors affect the quality of polyclonal responses, independent of
      age. Our work indicates that healthy elderly people are able to produce
      antibodies in response to vaccination with similar avidity and functional
      activity as young individuals, albeit at lower titers.

PMID- 22461904
TI  - JWA deficiency suppresses dimethylbenz[a]anthracene-phorbol ester induced skin
      papillomas via inactivation of MAPK pathway in mice.
AB  - Our previous studies indicated that JWA plays an important role in DNA damage
      repair, cell migration, and regulation of MAPKs. In this study, we investigated
      the role of JWA in chemical carcinogenesis using conditional JWA knockout
      (JWA(Delta2/Delta2)) mice and two-stage model of skin carcinogenesis. Our results
      indicated that JWA(Delta2/Delta2) mice were resistant to the development of skin
      papillomas initiated by 7, 12-dimethylbenz(a)anthracene (DMBA) followed by
      promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In JWA(Delta2/Delta2)
      mice, the induction of papilloma was delayed, and the tumor number and size were
      reduced. In primary keratinocytes from JWA(Delta2/Delta2) mice, DMBA exposure
      induced more intensive DNA damage, while TPA-promoted cell proliferation was
      reduced. The further mechanistic studies showed that JWA deficiency blocked TPA
      induced activation of MAPKs and its downstream transcription factor Elk1 both in
      vitro and in vivo. JWA(Delta2/Delta2) mice are resistance to tumorigenesis
      induced by DMBA/TPA probably through inhibition of transcription factor Elk1 via
      MAPKs. These results highlight the importance of JWA in skin homeostasis and in
      the process of skin tumor development.

PMID- 22461905
TI  - Erasing the epigenetic memory and beginning to switch--the onset of antigenic
      switching of var genes in Plasmodium falciparum.
AB  - Antigenic variation in Plasmodium falciparum is regulated by transcriptional
      switches among members of the var gene family, each expressed in a mutually
      exclusive manner and encoding a different variant of the surface antigens
      collectively named PfEMP1. Antigenic switching starts when the first merozoites
      egress from the liver and begin their asexual proliferation within red blood
      cells. By erasing the epigenetic memory we created parasites with no var
      background, similar to merozoites that egress from the liver where no var gene is
      expressed. Creating a null-var background enabled us to investigate the onset of
      antigenic switches at the early phase of infection. At the onset of switching,
      var transcription pattern is heterogeneous with numerous genes transcribed at low
      levels including upsA vars, a subtype that was implicated in severe malaria,
      which are rarely activated in growing cultures. Analysis of subsequent in vitro
      switches shows that the probability of a gene to turn on or off is not associated
      with its chromosomal position or promoter type per se but on intrinsic properties
      of each gene. We concluded that var switching is determined by gene specific
      associated switch rates rather than general promoter type or locus associated
      switch rates. In addition, we show that fine tuned reduction in var transcription
      increases their switch rate, indicating that transcriptional perturbation can
      alter antigenic switching.

PMID- 22461906
TI  - Activation of ERAD pathway by human hepatitis B virus modulates viral and
      subviral particle production.
AB  - Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of enveloped DNA
      viruses. It was previously shown that HBV can induce endoplasmic reticulum (ER)
      stress and activate the IRE1-XBP1 pathway of the unfolded protein response (UPR),
      through the expression of the viral regulatory protein X (HBx). However, it
      remained obscure whether or not this activation had any functional consequences
      on the target genes of the UPR pathway. Of these targets, the ER degradation
      enhancing, mannosidase-like proteins (EDEMs) are thought to play an important
      role in relieving the ER stress during UPR, by recognizing terminally misfolded
      glycoproteins and delivering them to the ER-associated degradation (ERAD). In
      this study, we investigated the role of EDEMs in the HBV life-cycle. We found
      that synthesis of EDEMs (EDEM1 and its homologues, EDEM2 and EDEM3) is
      significantly up-regulated in cells with persistent or transient HBV replication.
      Co-expression of the wild-type HBV envelope proteins with EDEM1 resulted in their
      massive degradation, a process reversed by EDEM1 silencing. Surprisingly, the
      autophagy/lysosomes, rather than the proteasome were involved in disposal of the
      HBV envelope proteins. Importantly, inhibition of the endogenous EDEM1 expression
      in HBV replicating cells significantly increased secretion of both, enveloped
      virus and subviral particles. This is the first report showing that HBV activates
      the ERAD pathway, which, in turn, reduces the amount of envelope proteins,
      possibly as a mechanism to control the level of virus particles in infected cells
      and facilitate the establishment of chronic infections.

PMID- 22461907
TI  - Predatory Bacteriovorax communities ordered by various prey species.
AB  - The role of predation in altering microbial communities has been studied for
      decades but few examples are known for bacterial predators. Bacteriovorax are
      halophilic prokaryotes that prey on susceptible gram-negative bacteria. We
      recently reported novel observations on the differential selection of
      Bacteriovorax phylotypes by two different prey, Vibrio parahaemolyticus and
      Vibrio vulnificus. However, the conclusion is restricted by the limited number of
      prey tested. In this study, we have conducted two independent investigations
      involving eight species of prey bacteria while using V. vulnificus and V.
      parahaemolytics as reference strains. Water samples collected from Dry Bar,
      Apalachicola Bay were used to establish microcosms which were respectively spiked
      with prey strains Vibrio cholerae, Escherichia coli or Pseudomonas putida to
      examine the response of native Bacteriovorax to freshwater bacteria. Indigenous
      Vibrio sp., Pseudoalteromonas sp., Photobacterium sp. and a clinical strain of V.
      vulnificus were also tested for the impact of saltwater prey on the Bacteriovorax
      community. At 24 hour intervals, optical density of the microcosm samples and the
      abundance of Bacteriovorax were measured over five days. The predominant
      Bacteriovorax plaques were selected and analyzed by 16S rRNA gene amplification
      and sequencing. In addition, the impacts of prey on predator population and
      bacterial community composition were investigated using culture independent
      denaturing gradient gel electrophoresis. Strikingly, Cluster IV was found
      consistently as the predominant phylotype produced by the freshwater prey. For
      all saltwater prey, subgroups of Bacteriovorax phylotype IX were the major
      predators recovered. The results suggest that prey is an important factor along
      with temperature, salinity and other environmental parameters in shaping
      Bacteriovorax communities in aquatic systems.

PMID- 22461908
TI  - Risk factors, molecular epidemiology and outcomes of ertapenem-resistant,
      carbapenem-susceptible Enterobacteriaceae: a case-case-control study.
AB  - BACKGROUND: Increasing prevalence of ertapenem-resistant, carbapenem-susceptible
      Enterobacteriaceae (ERE) in Singapore presents a major therapeutic problem. Our
      objective was to determine risk factors associated with the acquisition of ERE in
      hospitalized patients; to assess associated patient outcomes; and to describe the
      molecular characteristics of ERE. METHODS: A retrospective case-case-control
      study was conducted in 2009 at a tertiary care hospital. Hospitalized patients
      with ERE and those with ertapenem-sensitive Enterobacteriaceae (ESE) were
      compared with a common control group consisting of patients with no prior gram
      negative infections. Risk factors analyzed included demographics; co-morbidities;
      instrumentation and antibiotic exposures. Two parallel multivariate logistic
      regression models were performed to identify independent variables associated
      with ERE and ESE acquisition respectively. Clinical outcomes were compared
      between ERE and ESE patients. RESULTS: Twenty-nine ERE cases, 29 ESE cases and 87
      controls were analyzed. Multivariate logistic regression showed that previous
      hospitalization (Odds ratio [OR], 10.40; 95% confidence interval [CI], 2.19
      49.20) and duration of fluoroquinolones exposure (OR, 1.18 per day increase; 95%
      CI, 1.05-1.34) were unique independent predictors for acquiring ERE. Duration of
      4(th)-generation cephalosporin exposure was found to predict for ESE acquisition
      (OR, 1.63 per day increase; 95% CI, 1.05-2.54). In-hospital mortality rates and
      clinical response rates were significantly different between ERE and ESE groups,
      however ERE infection was not a predictor of mortality. ERE isolates were
      clonally distinct. Ertapenem resistance was likely to be mediated by the presence
      of extended-spectrum beta-lactamases or plasmid-borne AmpC in combination with
      impermeability due to porin loss and/or efflux pumps. CONCLUSION: Prior
      hospitalization and duration of fluoroquinolone treatment were predictors of ERE
      acquisition. ERE infections were associated with higher mortality rates and
      poorer clinical response rates when compared to ESE infections.

PMID- 22461909
TI  - Monoclonal antibodies to meningococcal factor H binding protein with overlapping
      epitopes and discordant functional activity.
AB  - BACKGROUND: Meningococcal factor H binding protein (fHbp) is a promising vaccine
      candidate. Anti-fHbp antibodies can bind to meningococci and elicit complement
      mediated bactericidal activity directly. The antibodies also can block binding of
      the human complement down-regulator, factor H (fH). Without bound fH, the
      organism would be expected to have increased susceptibility to bacteriolysis.
      Here we describe bactericidal activity of two anti-fHbp mAbs with overlapping
      epitopes in relation to their different effects on fH binding and bactericidal
      activity. METHODS AND PRINCIPAL FINDINGS: Both mAbs recognized prevalent fHbp
      sequence variants in variant group 1. Using yeast display and site-specific
      mutagenesis, binding of one of the mAbs (JAR 1, IgG3) to fHbp was eliminated by a
      single amino acid substitution, R204A, and was decreased by K143A but not by
      R204H or D142A. The JAR 1 epitope overlapped that of previously described mAb
      (mAb502, IgG2a) whose binding to fHbp was eliminated by R204A or R204H
      substitutions, and was decreased by D142A but not by K143A. Although JAR 1 and
      mAb502 appeared to have overlapping epitopes, only JAR 1 inhibited binding of fH
      to fHbp and had human complement-mediated bactericidal activity. mAb502 enhanced
      fH binding and lacked human complement-mediated bactericidal activity. To control
      for confounding effects of different mouse IgG subclasses on complement
      activation, we created chimeric mAbs in which the mouse mAb502 or JAR 1 paratopes
      were paired with human IgG1 constant regions. While both chimeric mAbs showed
      similar binding to fHbp, only JAR 1, which inhibited fH binding, had human
      complement-mediated bactericidal activity. CONCLUSIONS: The lack of human
      complement-mediated bactericidal activity by anti-fHbp mAb502 appeared to result
      from an inability to inhibit binding of fH. These results underscore the
      importance of inhibition of fH binding for anti-fHbp mAb bactericidal activity.

PMID- 22461910
TI  - FOXM1 induces a global methylation signature that mimics the cancer epigenome in
      head and neck squamous cell carcinoma.
AB  - The oncogene FOXM1 has been implicated in all major types of human cancer. We
      recently showed that aberrant FOXM1 expression causes stem cell compartment
      expansion resulting in the initiation of hyperplasia. We have previously shown
      that FOXM1 regulates HELLS, a SNF2/helicase involved in DNA methylation,
      implicating FOXM1 in epigenetic regulation. Here, we have demonstrated using
      primary normal human oral keratinocytes (NOK) that upregulation of FOXM1
      suppressed the tumour suppressor gene p16(INK4A) (CDKN2A) through promoter
      hypermethylation. Knockdown of HELLS using siRNA re-activated the mRNA expression
      of p16(INK4A) and concomitant downregulation of two DNA methyltransferases DNMT1
      and DNMT3B. The dose-dependent upregulation of endogenous FOXM1 (isoform B)
      expression during tumour progression across a panel of normal primary NOK strains
      (n = 8), dysplasias (n = 5) and head and neck squamous cell carcinoma (HNSCC)
      cell lines (n = 11) correlated positively with endogenous expressions of HELLS,
      BMI1, DNMT1 and DNMT3B and negatively with p16(INK4A) and involucrin. Bisulfite
      modification and methylation-specific promoter analysis using absolute
      quantitative PCR (MS-qPCR) showed that upregulation of FOXM1 significantly
      induced p16(INK4A) promoter hypermethylation (10-fold, P<0.05) in primary NOK
      cells. Using a non-bias genome-wide promoter methylation microarray profiling
      method, we revealed that aberrant FOXM1 expression in primary NOK induced a
      global hypomethylation pattern similar to that found in an HNSCC (SCC15) cell
      line. Following validation experiments using absolute qPCR, we have identified a
      set of differentially methylated genes, found to be inversely correlated with in
      vivo mRNA expression levels of clinical HNSCC tumour biopsy samples. This study
      provided the first evidence, using primary normal human cells and tumour tissues,
      that aberrant upregulation of FOXM1 orchestrated a DNA methylation signature that
      mimics the cancer methylome landscape, from which we have identified a unique
      FOXM1-induced epigenetic signature which may have clinical translational
      potentials as biomarkers for early cancer screening, diagnostic and/or
      therapeutic interventions.

PMID- 22461911
TI  - TNF-alpha is involved in the abnormal thymocyte migration during experimental
      Trypanosoma cruzi infection and favors the export of immature cells.
AB  - Previous studies revealed a significant production of inflammatory cytokines
      together with severe thymic atrophy and thymocyte migratory disturbances during
      experimental Chagas disease. Migratory activity of thymocytes and mature T cells
      seem to be finely tuned by cytokines, chemokines and extracellular matrix (ECM)
      components. Systemic TNF-alpha is enhanced during infection and appears to be
      crucial in the response against the parasite. However, it also seems to be
      involved in disease pathology, since it is implicated in the arrival of T cells
      to effector sites, including the myocardium. Herein, we analyzed the role of TNF
      alpha in the migratory activity of thymocytes in Trypanosoma cruzi (T. cruzi)
      acutely-infected mice. We found increased expression and deposition of TNF-alpha
      in the thymus of infected animals compared to controls, accompanied by increased
      co-localization of fibronectin, a cell migration-related ECM molecule, whose
      contents in the thymus of infected mice is also augmented. In-vivo studies showed
      an enhanced export of thymocytes in T. cruzi-infected mice, as ascertained by
      intrathymic injection of FITC alone or in combination with TNF-alpha. The
      increase of immature CD4(+)CD8(+) T cells in secondary lymphoid organs was even
      more clear-cut when TNF-alpha was co-injected with FITC. Ex-vivo transmigration
      assays also revealed higher number of migrating cells when TNF-alpha was added
      onto fibronectin lattices, with higher input of all thymocyte subsets, including
      immature CD4(+)CD8(+). Infected animals also exhibit enhanced levels of
      expression of both mRNA TNF-alpha receptors in the CD4(+)CD8(+) subpopulation.
      Our findings suggest that in T. cruzi acute infection, when TNF-alpha is
      complexed with fibronectin, it favours the altered migration of thymocytes,
      promoting the release of mature and immature T cells to different compartments of
      the immune system. Conceptually, this work reinforces the notion that thymocyte
      migration is a multivectorial biological event in health and disease, and that
      TNF-alpha is a further player in the process.

PMID- 22461912
TI  - Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with
      breast cancer.
AB  - BACKGROUND: Research into the etiology of breast cancer has recently focused on
      the role of the immunity and inflammation. The proinflammatory cytokines IL-17A
      and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL
      17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case
      control study was conducted in Chinese Han women. METHODOLOGY AND PRINCIPAL
      FINDINGS: We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A
      (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511,
      rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491
      women with breast cancer and 502 healthy individuals. The genotypes were
      determined using the SNaPshot technique. The differences in the genotypic
      distribution between breast cancer patients and healthy controls were analyzed
      with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of
      the AA genotype was higher in patients than controls (P = 0.0016). The clinical
      features analysis demonstrated significant associations between IL-17 SNPs and
      tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor
      receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the
      haplotype analysis indicated that the frequency of the haplotype
      A(rs2275913)G(rs3819025)G(rs3748067), located in the IL-17A linkage
      disequilibrium (LD) block, was higher in patients than in controls (P = 0.0471
      after correction for multiple testing). CONCLUSIONS AND SIGNIFICANCE: Our results
      suggested that SNPs in IL-17A but not IL-17F were associated with the risk of
      breast cancer. Both IL-17A and IL-17F gene polymorphisms may provide valuable
      information for predicting the prognosis of breast cancer in Chinese women.

PMID- 22461914
TI  - Overview of Project BETA: Best practices in Evaluation and Treatment of
      Agitation.

PMID- 22461913
TI  - A classification method based on principal components of SELDI spectra to
      diagnose of lung adenocarcinoma.
AB  - PURPOSE: Lung cancer is the leading cause of cancer death worldwide, but
      techniques for effective early diagnosis are still lacking. Proteomics technology
      has been applied extensively to the study of the proteins involved in
      carcinogenesis. In this paper, a classification method was developed based on
      principal components of surface-enhanced laser desorption/ionization (SELDI)
      spectral data. This method was applied to SELDI spectral data from 71 lung
      adenocarcinoma patients and 24 healthy individuals. Unlike other peak-selection
      based methods, this method takes each spectrum as a unity. The aim of this paper
      was to demonstrate that this unity-based classification method is more robust and
      powerful as a method of diagnosis than peak-selection-based methods. RESULTS: The
      results showed that this classification method, which is based on principal
      components, has outstanding performance with respect to distinguishing lung
      adenocarcinoma patients from normal individuals. Through leaving-one-out, 19
      fold, 5-fold and 2-fold cross-validation studies, we found that this
      classification method based on principal components completely outperforms peak
      selection-based methods, such as decision tree, classification and regression
      tree, support vector machine, and linear discriminant analysis. CONCLUSIONS AND
      CLINICAL RELEVANCE: The classification method based on principal components of
      SELDI spectral data is a robust and powerful means of diagnosing lung
      adenocarcinoma. We assert that the high efficiency of this classification method
      renders it feasible for large-scale clinical use.

PMID- 22461915
TI  - Medical evaluation and triage of the agitated patient: consensus statement of the
      american association for emergency psychiatry project Beta medical evaluation
      workgroup.
AB  - Numerous medical and psychiatric conditions can cause agitation; some of these
      causes are life threatening. It is important to be able to differentiate between
      medical and nonmedical causes of agitation so that patients can receive
      appropriate and timely treatment. This article aims to educate all clinicians in
      nonmedical settings, such as mental health clinics, and medical settings on the
      differing levels of severity in agitation, basic triage, use of de-escalation,
      and factors, symptoms, and signs in determining whether a medical etiology is
      likely. Lastly, this article focuses on the medical workup of agitation when a
      medical etiology is suspected or when etiology is unclear.

PMID- 22461916
TI  - Psychiatric evaluation of the agitated patient: consensus statement of the
      american association for emergency psychiatry project Beta psychiatric evaluation
      workgroup.
AB  - It is difficult to fully assess an agitated patient, and the complete psychiatric
      evaluation usually cannot be completed until the patient is calm enough to
      participate in a psychiatric interview. Nonetheless, emergency clinicians must
      perform an initial mental status screening to begin this process as soon as the
      agitated patient presents to an emergency setting. For this reason, the
      psychiatric evaluation of the agitated patient can be thought of as a 2-step
      process. First, a brief evaluation must be aimed at determining the most likely
      cause of agitation, so as to guide preliminary interventions to calm the patient.
      Once the patient is calmed, more extensive psychiatric assessment can be
      completed. The goal of the emergency assessment of the psychiatric patient is not
      necessarily to obtain a definitive diagnosis. Rather, ascertaining a differential
      diagnosis, determining safety, and developing an appropriate treatment and
      disposition plan are the goals of the assessment. This article will summarize
      what components of the psychiatric assessment can and should be done at the time
      the agitated patient presents to the emergency setting. The complete psychiatric
      evaluation of the patient whose agitation has been treated successfully is beyond
      the scope of this article and Project BETA (Best practices in Evaluation and
      Treatment of Agitation), but will be outlined briefly to give the reader an
      understanding of what a full psychiatric assessment would entail. Other issues
      related to the assessment of the agitated patient in the emergency setting will
      also be discussed.

PMID- 22461917
TI  - Verbal De-escalation of the Agitated Patient: Consensus Statement of the American
      Association for Emergency Psychiatry Project BETA De-escalation Workgroup.
AB  - Agitation is an acute behavioral emergency requiring immediate intervention.
      Traditional methods of treating agitated patients, ie, routine restraints and
      involuntary medication, have been replaced with a much greater emphasis on a
      noncoercive approach. Experienced practitioners have found that if such
      interventions are undertaken with genuine commitment, successful outcomes can
      occur far more often than previously thought possible. In the new paradigm, a 3
      step approach is used. First, the patient is verbally engaged; then a
      collaborative relationship is established; and, finally, the patient is verbally
      de-escalated out of the agitated state. Verbal de-escalation is usually the key
      to engaging the patient and helping him become an active partner in his
      evaluation and treatment; although, we also recognize that in some cases
      nonverbal approaches, such as voluntary medication and environment planning, are
      also important. When working with an agitated patient, there are 4 main
      objectives: (1) ensure the safety of the patient, staff, and others in the area;
      (2) help the patient manage his emotions and distress and maintain or regain
      control of his behavior; (3) avoid the use of restraint when at all possible; and
      (4) avoid coercive interventions that escalate agitation. The authors detail the
      proper foundations for appropriate training for de-escalation and provide
      intervention guidelines, using the "10 domains of de-escalation."

PMID- 22461918
TI  - The psychopharmacology of agitation: consensus statement of the american
      association for emergency psychiatry project Beta psychopharmacology workgroup.
AB  - Agitation is common in the medical and psychiatric emergency department, and
      appropriate management of agitation is a core competency for emergency
      clinicians. In this article, the authors review the use of a variety of first
      generation antipsychotic drugs, second-generation antipsychotic drugs, and
      benzodiazepines for treatment of acute agitation, and propose specific guidelines
      for treatment of agitation associated with a variety of conditions, including
      acute intoxication, psychiatric illness, delirium, and multiple or idiopathic
      causes. Pharmacologic treatment of agitation should be based on an assessment of
      the most likely cause of the agitation. If agitation results from a delirium or
      other medical condition, clinicians should first attempt to treat the underlying
      cause instead of simply medicating with antipsychotics or benzodiazepines.

PMID- 22461919
TI  - Use and avoidance of seclusion and restraint: consensus statement of the american
      association for emergency psychiatry project Beta seclusion and restraint
      workgroup.
AB  - Issues surrounding reduction and/or elimination of episodes of seclusion and
      restraint for patients with behavioral problems in crisis clinics, emergency
      departments, inpatient psychiatric units, and specialized psychiatric emergency
      services continue to be an area of concern and debate among mental health
      clinicians. An important underlying principle of Project BETA (Best practices in
      Evaluation and Treatment of Agitation) is noncoercive de-escalation as the
      intervention of choice in the management of acute agitation and threatening
      behavior. In this article, the authors discuss several aspects of seclusion and
      restraint, including review of the Centers for Medicare and Medicaid Services
      guidelines regulating their use in medical behavioral settings, negative
      consequences of this intervention to patients and staff, and a review of quality
      improvement and risk management strategies that have been effective in decreasing
      their use in various treatment settings. An algorithm designed to help the
      clinician determine when seclusion or restraint is most appropriate is
      introduced. The authors conclude that the specialized psychiatric emergency
      services and emergency departments, because of their treatment primarily of acute
      patients, may not be able to entirely eliminate the use of seclusion and
      restraint events, but these programs can adopt strategies to reduce the
      utilization rate of these interventions.

PMID- 22461920
TI  - Evaluation of an emergency department educational campaign for recognition of
      suicidal patients.
AB  - INTRODUCTION: To evaluate the impact of a simple emergency department (ED)-based
      educational intervention designed to assist ED providers in detecting occult
      suicidal behavior in patients who present with complaints that are not related to
      behavioral health. METHODS: Staff from 5 ED sites participated in the study. Four
      ED staff members were exposed to a poster and clinical guide for the recognition
      and management of suicidal patients. Staff members in 1 ED were not exposed to
      training material and served as a comparator group. RESULTS: At baseline, only
      36% of providers reported that they had sufficient training in how to assess
      level of suicide risk in patients. Greater than two thirds of providers agreed
      that additional training would be helpful in assessing the level of patient
      suicide risk. More than half of respondents who were exposed to the intervention
      (51.6%) endorsed increased knowledge of suicide risk during the study period,
      while 41% indicated that the intervention resulted in improved skills in managing
      suicidal patients. CONCLUSION: This brief, free intervention appeared to have a
      beneficial impact on providers' perceptions of how well suicidality was
      recognized and managed in the ED.

PMID- 22461921
TI  - Impact of the mental healthcare delivery system on california emergency
      departments.
AB  - INTRODUCTION: This is an observational study of emergency departments (ED) in
      California to identify factors related to the magnitude of ED utilization by
      patients with mental health needs. METHODS: In 2010, an online survey was
      administered to ED directors in California querying them about factors related to
      the evaluation, timeliness to appropriate psychiatric treatment, and disposition
      of patients presenting to EDs with psychiatric complaints. RESULTS: One hundred
      twenty-three ED directors from 42 of California's 58 counties responded to the
      survey. The mean number of hours it took for psychiatric evaluations to be
      completed in the ED, from the time referral was placed to completed evaluation,
      was 5.97 hours (95% confidence interval [CI], 4.82-7.13). The average wait time
      for adult patients with a primary psychiatric diagnosis in the ED, once the
      decision to admit was made until placement into an inpatient psychiatric bed or
      transfer to an appropriate level of care, was 10.05 hours (95% CI, 8.69-11.52).
      The average wait time for pediatric patients with a primary psychiatric diagnosis
      was 12.97 hours (95% CI, 11.16-14.77). The most common reason reported for
      extended ED stays for this patient population was lack of inpatient psychiatric
      beds. CONCLUSION: The extraordinary wait times for patients with mental illness
      in the ED, as well as the lack of resources available to EDs for effectively
      treating and appropriately placing these patients, indicate the existence of a
      mental health system in California that prevents patients in acute need of
      psychiatric treatment from getting it at the right time, in the right place.

PMID- 22461922
TI  - Life in the inner city.

PMID- 22461923
TI  - Bath salts: the ivory wave of trouble.

PMID- 22461924
TI  - Dose-dependent response to cyclodextrin infusion in a rat model of verapamil
      toxicity.
AB  - INTRODUCTION: Sulfobutylether-beta-cyclodextrin (SBE-CD) is a pharmaceutical
      excipient known to bind verapamil. Following intravenous administration,
      clearance of SBE-CD approximates glomerular filtration rate. We hypothesized that
      infusion of SBE-CD would increase time to asystole in a rat model of verapamil
      toxicity in a dose-dependent manner. The objective was to demonstrate the effect
      of a range of SBE-CD concentrations in a rat model of verapamil toxicity.
      METHODS: Twenty-five Wistar rats were allocated to control or 1 of 4 intervention
      groups. All received ketamine and diazepam anesthesia followed by verapamil
      infusion 32 mg/kg/h. The verapamil infusion for the intervention groups was
      premixed with SBE-CD in a 1:1, 1:2, 1:4, or 1:8 molar ratio (verapamil to SBE
      CD). The control group infusion did not contain SBE-CD. Additional saline or
      water was added to the infusion so that the total volume infused was the same
      across groups, and the osmolality was maintained as close to physiologic as
      possible. Heart rate, respiratory rate, and temperature were monitored. The
      primary endpoint was time to asystole. RESULTS: Verapamil coinfused with SBE-CD
      in a molar ratio of 1:4 resulted in prolonged time to asystole compared to
      control (21.2 minutes vs 17.6 minutes, P < 0.05). There were no differences in
      time to asystole between control and any other intervention group. There was no
      significant difference in time to apnea between control and any intervention
      group. We assessed the effect of a range of SBE-CD concentrations and identified
      1 concentration that prolonged time to asystole. Mechanisms that may explain this
      effect include optimal volume expansion with a hyperosmolar cyclodextrin
      containing solution, complexation of verapamil within the hydrophobic
      cyclodextrin pore, and/or complexation within micelle-like aggregates of
      cyclodextrin. However, mechanistic explanations for the observed findings are
      speculative at this point. CONCLUSION: The 1:4 verapamil to SBE-CD concentration
      was modestly effective with SBE-CD concentrations above and below this range
      demonstrating nonstatistically significant improvements in time to asystole.

PMID- 22461925
TI  - The role for coagulation markers in mild snakebite envenomations.
AB  - INTRODUCTION: The majority of patients seeking medical treatment for snakebites
      do not suffer from severe envenomation. However, no guidelines exist for ordering
      coagulation markers in patients with minimal or moderate envenomation, nor in
      those who do not receive antivenom. In this study, we sought to determine whether
      it was possible to limit the practice of ordering coagulation studies to those
      patients suffering severe envenomation, rattlesnake envenomation, or both.
      METHODS: A retrospective chart review was performed on all cases of crotalid
      snakebite presenting to an adult emergency department (ED) from April 1998 to
      June 2006. Each chart was abstracted for patient's age, gender, type of snake (if
      known), severity of envenomation at initial presentation, coagulation test
      results, whether antivenom was administered, and whether the patient was
      admitted. RESULTS: Over an approximately 8-year period, 131 snakebite cases
      presented that met the inclusion criteria, of which 35 (26.7%) had some type of
      coagulation marker abnormality. Limiting coagulation testing to patients
      suffering severe envenomation or rattlesnake envenomation would have resulted in
      failure to identify 89% or 77%, respectively, of the 35 patients who were found
      to have at least 1 abnormal coagulation marker. CONCLUSION: Our study failed to
      identify a subset of patients that could be defined as low risk or for whom
      coagulation marker testing could be foregone. This study suggests that
      coagulation tests should be routinely performed on all patients presenting to the
      ED with complaints of envenomation by copperheads, moccasins, or rattlesnakes.
      Further clarification of when coagulation markers are indicated may require a
      prospective study that standardizes snake identification and the timing of
      coagulation marker testing.

PMID- 22461926
TI  - Coagulopathy: the most important thing we still don't know about snakebite.

PMID- 22461927
TI  - Massive atropine eye drop ingestion treated with high-dose physostigmine to avoid
      intubation.
AB  - CASE: A 34-year-old male presented after ingesting 150 mg of atropine. He had
      altered mental status, sinus tachycardia, dry mucosa, flushed skin, and
      hyperthermia. Sequential doses of physostigmine, totaling 14 mg, were successful
      in reversing antimuscarinic toxicity and prevented the need to perform airway
      control with endotracheal intubation. At completion of treatment, heart rate and
      mental status had improved, and intubation was never performed. DISCUSSION:
      Atropine causes anticholinergic toxicity; physostigmine reverses this by
      inhibiting acetylcholinesterase. Atropine eye drop ingestions are rare. The 14 mg
      of physostigmine administered is much higher than typical dosing. It is likely
      the physostigmine prevented intubation. Atropine eye drops can be dangerous, and
      physostigmine should be considered in treatment.

PMID- 22461928
TI  - A pain in the wrist: stingray envenomation.

PMID- 22461930
TI  - Aortocaval fistula.

PMID- 22461929
TI  - Letters to the editor.

PMID- 22461931
TI  - Recognizing infective endocarditis in the emergency department.
AB  - A 52-year-old Caucasian male presented to the emergency department complaining of
      nontraumatic painful swelling and redness of the distal left fourth finger for 2
      days, associated with malaise and subjective fever. The patient denied medical
      history, drugs, tobacco, or alcohol use.

PMID- 22461932
TI  - Acute appendicitis from metastatic small cell lung cancer.

PMID- 22461933
TI  - Intussusception Status-Post Roux-en-Y Gastric Bypass.

PMID- 22461934
TI  - More than Just another Pulmonary Embolism.

PMID- 22461935
TI  - Delayed presentation of sigmoid volvulus in a young woman.
AB  - Volvulus is an unusual condition in Western countries, generally isolated to
      elderly patients with multiple comorbidities. This report describes an unusual
      case of a very large gangrenous sigmoid volvulus in a young, otherwise healthy 25
      year-old female. A review of the diagnosis and management is subsequently
      described. Without a consideration of the atypical demographics for sigmoid
      volvulus, the case illustrates the potential morbidity due to a delayed
      diagnosis. Early identification and management are crucial in treating sigmoid
      volvulus before the appearance of gangrene and necrosis, thereby avoiding further
      complications and associated mortality.

PMID- 22461936
TI  - Right-sided sigmoid diverticular perforation.
AB  - Diverticulosis is a common disorder among geriatric patients, of whom 10% to 25%
      go on to develop diverticulitis. Known complications of diverticulitis include
      formation of phlegmon, fistula, bowel obstruction, bleeding, perforation, and
      colonic abscess. A less common complication is perforation with formation of an
      extra-abdominal necrotizing abscess. This case is a report of an 83-year-old
      female who presented to the emergency department with a necrotizing abdominal
      wall abscess secondary to right-sided diverticular microperforation.

PMID- 22461937
TI  - Massive gastric distension from chronic intestinal pseudo-obstruction.

PMID- 22461938
TI  - Diplopia from subacute bilateral subdural hematoma after spinal anesthesia.
AB  - Subdural hematoma (SDH) is a rare, but life-threatening complication of spinal
      anesthesia. Subdural hematoma resulting from this procedure could present with
      vague symptoms such as chronic headache and could easily be missed. Chronic
      headache is one of the symptoms of chronic SDH in postpartum women. Diplopia as
      the presenting complaint in SDH secondary to peripartum spinal anesthesia has
      not, to our knowledge, been previously reported. Here, we report a case of
      diplopia secondary to postpartum subacute bilateral SDHs with transtentorial
      herniation after spinal anesthesia in a healthy primagravid 25-year-old woman.
      SDH can expand gradually and the initial symptoms might be subtle as in our case,
      despite critically high intracranial pressure.

PMID- 22461939
TI  - Therapeutic hypothermia for acute air embolic stroke.

PMID- 22461940
TI  - Benign nuchal rigidity: the emergency department evaluation of acute prevertebral
      calcific tendonitis.
AB  - Acute prevertebral calcific tendonitis (APCT) is a rare condition, the exact
      incidence of which is unknown. It is of particular interest to the emergency
      physician owing to the other potentially devastating conditions in the
      differential diagnosis of neck stiffness and/or odynophagia (including
      retropharyngeal abscess, infectious spondylitis, and meningitis.) In contrast,
      APCT has a benign clinical course and can be easily managed in the emergency
      department. We will present a case of APCT, followed by a brief discussion of the
      disease and current literature.

PMID- 22461941
TI  - Tension gastrothorax in a child presenting with abdominal pain.
AB  - A 4-year-old girl was brought to our hospital by her parents because of abdominal
      pain. She had suffered minor trauma after rolling from her standard-height bed 2
      days prior. Vital signs were appropriate for age. Physical examination was
      remarkable for decreased breath sounds to the left side of the chest. A chest
      radiograph (Figure) demonstrated a large gas-filled structure in the left side of
      the chest with mediastinal shift.

PMID- 22461942
TI  - Kohler's Disease.
AB  - We present a pediatric case report of foot pain due to Kohler's disease.

PMID- 22461943
TI  - Chemical burn secondary to propofol extravasation.

PMID- 22461944
TI  - Unilateral internuclear ophthalmoplegia after minor head injury.
AB  - Internuclear ophthalmoplegia is a rare condition caused by injury to the medial
      longitudinal fasciculus in the brainstem. It usually occurs in conditions such as
      stroke or multiple sclerosis and is extremely rare after head injury. We report a
      case of unilateral internuclear ophthalmoplegia, which occurred after a minor
      head injury in a young male. His only symptoms were headache and diplopia. He was
      treated conservatively, and his symptoms settled after 3 months.

PMID- 22461945
TI  - Cervical ectopic pregnancy.

PMID- 22461946
TI  - Erosion of embolization coils into the renal collecting system mimicking stone.
AB  - Urinary tract interventions can lead to multiple complications in the renal
      collecting system, including retained foreign bodies from endourologic or
      percutaneous procedures, such as stents, nephrostomy tubes, and others. We report
      a case of very delayed erosion of embolization coils migrating into the renal
      pelvis, acting as a nidus for stone formation, causing mild obstruction and
      finally leading to gross hematuria roughly 18 years post transarterial
      embolization. History is significant for a remote unsuccessful endopyelotomy
      attempt that required an urgent embolization.

PMID- 22461947
TI  - Testicular Compromise due to Inguinal Hernia.
AB  - A 34-year-old male presented to the emergency department with a 3-hour complaint
      of pain in the right lower quadrant and right testicle. He stated that his pain
      began suddenly while standing at work. On physical examination, he had a small,
      firm, unreducible bulge in his right inguinal canal and an enlarged right
      scrotum. The patient was placed in trendelenburg position; intravenous fentanyl,
      valium, and dilaudid were administered; and surgery consult was obtained. A
      testicular ultrasonogram (Figure) was obtained owing to continued pain in the
      right scrotum and inability to evaluate the testicle. After viewing the
      ultrasound pattern, the patient was promptly taken to the operating room 6 hours
      after onset of symptoms.

PMID- 22461948
TI  - Haemophilus influenzae Sepsis and Placental Abruption in an Unvaccinated
      Immigrant.
AB  - BACKGROUND: Haemophilus influenzae infections have declined dramatically in the
      United States since implementation of the conjugate vaccine. However, in
      countries where widespread immunization is not routine, H influenzae remains a
      significant cause of morbidity and mortality. We report a case of a previously
      unvaccinated immigrant with confirmed H influenzae sepsis and placental abruption
      leading to spontaneous abortion. OBJECTIVES: To alert emergency medicine
      practitioners that H influenzae should be recognized as a maternal, fetal, and
      neonatal pathogen. Clinicians should consider this diagnosis in immigrants
      presenting with uncertain vaccination history, as H influenzae can cause
      significant morbidity and mortality. CASE PRESENTATION: A 36-year-old female was
      referred to our emergency department (ED) with lower abdominal pain with some
      vaginal spotting. The patient had an initial visit with normal laboratory
      investigations and normal imaging results, with complete resolution of symptoms.
      The patient returned to the ED with sudden onset of vaginal bleeding and
      abdominal pain. She presented at this time with sepsis, which progressed to
      septic shock, causing placental abruption and ultimately, spontaneous abortion.
      The patient was treated with pressors and antibiotics and was admitted to the
      medical intensive care unit where she received ampicillin, gentamycin, and
      clindamycin for suspected chorioamnionitis. The patient's blood cultures came
      back positive after 1 day for H influenzae. The patient did well and was
      discharged from the hospital 4 days later. CONCLUSION: Haemophilus influenzae
      should be recognized as a neonatal and maternal pathogen. Clinicians should
      consider this diagnosis in immigrants presenting with uncertain vaccination
      history, especially in pregnant females, as H influenzae can cause significant
      morbidity and mortality.

PMID- 22461949
TI  - Dermatomyositis with extensive calcification in an adult.
AB  - This report reviews a case of dermatomyositis presenting with weakness and
      extensive calcification in an adult. While dermatomyositis is not uncommon in
      adults, it is uncommon for calcifications to be present. Children develop
      calcifications more frequently than adults. When present in adults, small
      calcifications on areas of frequent trauma such as elbows and fingers are more
      common. However, this patient presented with large calcified deposits in his
      abdomen and extremities. His treatment and course are described.

PMID- 22461950
TI  - Combining the external fixation and microsurgical osteoseptocutaneous flap
      transplantation methods for limb salvage.
AB  - BACKGROUND: The correction of large area limb defects that are the result of
      congenital abnormalities, traumatic injury, inflammation, or tumors is a
      challenging task for clinicians. The need to restore the physical, mechanical,
      and cosmetic aspects of the limb results in a difficult balancing act between
      deformity repair and tissue reconstruction, between the soft tissue and bone
      reconstructions, and between the physical, mechanical, and esthetic restorations.
      METHODS: Between 2003 and 2011, 59 patients with large area limb defects
      underwent 1- or 2-stage reconstructions that combined external fixation with
      microsurgical osteocutaneous flap transfer. In 1-stage reconstruction, the
      Ilizarov device was applied as a dynamic fixator before pathological bone
      resection. Free osteoseptocutaneous flap transplantation was then performed. This
      is suitable for simple bone defects with temporary continuity such as
      osteomyelitis. In 2-stage reconstruction, the Ilizarov device served as both an
      external fixator and tractor before debridement. This was followed by secondary
      free osteoseptocutaneous flap transplantation. This is suitable for complex bone
      defects like those seen in pseudarthrosis, fractures, and tumors. In all cases,
      the Ilizarov device was kept in position until bone union was confirmed by both
      surgeons and the radiologist. RESULTS: All patients survived the procedure. Using
      Paley's classification system, there were 3 (5.1%) true complications, 2 (3.4%)
      obstacles, and 5 (8.5%) problems. CONCLUSIONS: The staged methods allowed the
      seamless repair and reconstruction of bone and combined it with soft tissue
      reconstruction. This simultaneously restored the limb function and esthetics with
      minimal costs in terms of time, money, and patient pain.

PMID- 22461951
TI  - The component separation index: a standardized biometric identity in abdominal
      wall reconstruction.
AB  - OBJECTIVE: Reconstruction of traumatic ventral hernias often requires additional
      techniques to the abdominal wall component separation, such as the use of
      interpositional reconstruction with an acellular dermal matrix or other mesh to
      bridge the defect. METHODS: We have developed a new value termed the "Component
      Separation Index" to evaluate ventral hernia defects. Choosing a fixed point on a
      preoperative axial computed tomographic scan (aorta) and the medial leading edges
      of the rectus abdominus muscles, we determined the angle of diastasis of the
      hernia. This angle is divided by 360 degrees  giving a relative value of the
      transverse defect size as compared to the estimated circular body habitus for
      that specific patient. A retrospective review of 36 cases of ventral hernia
      repairs was performed. The Component Separation Index was calculated from the
      preoperative computed tomographic scans obtained before repair. Group 1 (n = 18)
      required component separation for closure. Group 2 (n = 18) required component
      separation and placement of interpositional mesh to span the hernia defect.
      RESULTS: The Component Separation Index values were then compared using the
      student t test for each group. The mean Component Separation Index for group 1
      was 0.11 with standard deviation of 0.06. The mean Component Separation Index for
      group 2 was 0.21 with standard deviation of 0.04 (P < .0001). As this value
      approaches 0.21, the likelihood of an interpositional repair in addition to
      component separation becomes much greater. CONCLUSIONS: While there is no
      substitute for clinical acumen when evaluating these defects, objective
      measurements can provide a valuable additional tool for the surgeon facing these
      challenging cases.

PMID- 22461952
TI  - A split forehead flap for the treatment of resistant bilateral upper and lower
      eyelid ectropion postburn injury.
AB  - OBJECTIVE: The aim of this surgical procedure was to definitively correct severe
      recurrent upper and lower bilateral eyelid ectropion after 2 attempts with full
      thickness skin grafts. It was necessary to repair all 4 eyelids with forehead
      skin. Middle lamella support was required. METHODS: Bilateral median forehead
      flaps, which were well vascularized by the supratrochlear vessels, were chosen
      for this procedure to utilize the readily available forehead tissue. The median
      forehead flap can be easily positioned to cover the entire eyelid. Furthermore,
      the flap could be split in half, without the risk of vascular compromise. Middle
      lamella support was provided with a cartilage graft from the nasal septum.
      RESULTS: At 4 months, the patient no longer suffered from exposure keratopathy
      and both forehead flaps had healed well. At 12 months, the functional and
      cosmetic outcomes of this procedure were acceptable. CONCLUSIONS: This method of
      surgery can be effective in the young, in whom the Mustarde cheek advancement
      fails, or when there is little available unburnt tissue. It can be used as an
      alternative to a forehead flap when both upper and lower eyelids are damaged
      bilaterally. The split forehead flap definitively corrected the ectropion in this
      case.

PMID- 22461953
TI  - Gastrointestinal absorption and biological activities of serine and cysteine
      proteases of animal and plant origin: review on absorption of serine and cysteine
      proteases.
AB  - Research has confirmed that peptides and larger protein molecules pass through
      the mucosal barrier of the gastrointestinal tract. Orally administered serine and
      cysteine proteases of plant and animal origin also reach blood and lymph as
      intact, high molecular weight and physiologically active protein molecules. Their
      absorption may be supported by a self-enhanced paracellular transport mechanism
      resulting in sub-nanomolar concentration of transiently free protease molecules
      or, in a complex with anti-proteases, at higher concentrations. Data from
      pharmacokinetic investigations reveals dose linearity for maximum plasma levels
      of free proteases not unusual for body proteases and a high inter-individual
      variability. There is no interference with each other after oral administration
      of protease combinations, and absorption follows an unusual invasion and
      elimination kinetic due to slow velocity of absorption and a fast 100% protein
      binding to anti-proteases. Oral application of proteases leads to increased
      proteolytic serum activity and increased plasma concentrations of the
      corresponding anti-proteases. Their biological activity is determined by their
      proteolytic activity as free proteases on soluble peptides/proteins or cell
      surface receptors (e.g. protease activated receptors) and their activity in the
      complex formed with their specific and/or unspecific anti-proteases. The anti
      protease-complexes, during immune reaction and injuries often loaded with
      different cytokines, are cleared from body fluids and tissue by receptor mediated
      endocytosis on hepatocytes and/or blood cells. Oral administration of enteric
      coated tablets containing proteolytic enzymes of plant and animal origin may be a
      safe method to stabilize, positively influence or enhance physiological and
      immunological processes during disease processes and in healthy consumers.

PMID- 22461955
TI  - Inhibitory effects of salviae miltiorrhizae radix (danshen) and puerariae lobatae
      radix (gegen) in carbachol-induced rat detrusor smooth muscle contractility.
AB  - Both danshen (D) and gegen (G) have proven relaxant effects on vascular smooth
      muscle, thus their potential bladder inhibitory effects have impending interests
      in urology. The aim of this study was to demonstrate the novel effects of D and G
      on detrusor smooth muscle contractility. Urothelium-intact (+UE) and urothelium
      denuded (-UE) detrusor strips were isolated from the rat. Isometric tension was
      measured using a myograph system. Carbachol (CCh) was used to pre-contract the
      detrusor strips prior to stepwise relaxation by adding extracts of D, G, and a DG
      (7:3) formulation. Tonic relaxation level and phasic contractile activity under
      the herbal treatments were analyzed. There was no difference in the herbal
      effects between +UE and -UE strips. D alone induced a much smaller relaxation
      than G alone or DG. G alone also suppressed phasic amplitude but not phasic
      frequency while DG suppressed both parameters. D and G acted synergistically to
      yield the observed effects on detrusor smooth muscle. The findings showed that
      the DG formulation were able to relax the detrusor as well as suppress phasic
      contractions, both actions important in maintaining normal bladder filling and
      urine storage processes. Hence DG may have new application in the management of
      bladder disorders.

PMID- 22461954
TI  - The link between angiotensin II-mediated anxiety and mood disorders with NADPH
      oxidase-induced oxidative stress.
AB  - The renin-angiotensin system (RAS) and its active peptide angiotensin II (AngII)
      have major involvements not only in hypertension but also in mood and anxiety
      disorders. Substantial evidence supports the notion that AngII acts as a
      neuromodulator in the brain. In this review, we provide an overview of the link
      between the RAS and anxiety or mood disorders, and focus on recent advances in
      the understanding of AngII-linked, NADPH oxidase-derived oxidative stress in the
      central nervous system, which may underlie pathogenesis of mood and anxiety
      disorders.

PMID- 22461956
TI  - Does anticipatory sweating occur prior to fluid consumption?
AB  - The purpose of this study was to examine if anticipatory sweating occurs prior to
      fluid consumption in dehydrated subjects. It was hypothesized that there would
      first be an anticipatory response to the sight of water, and then with drinking,
      a second response caused by mechanical stimulation of oropharyngeal nerves.
      Dehydrated subjects (n=19) sat in a heat chamber for 30 minutes. At minute 15, a
      resistance hygrometer capsule was attached and sweat rate was measured every 3
      seconds. At minute 35:00, a researcher entered the room with previously measured
      water (2 ml/kg euhydrated body weight). At minute 35:30, the subject was allowed
      to drink. Data collection continued for 5 minutes post consumption. As expected,
      16 of the 19 subjects responded to oropharyngeal stimuli with increased sweat
      rate. However, the new finding was that a majority (12 of 19) also showed an
      anticipatory sweating response prior to fluid consumption. Subjects were divided
      into 4 groups based on the magnitude of the sweating response. Strong responders'
      (n=4) anticipatory response accounted for 50% or more of the total change in
      sweat rate. Moderate responders' (n=4) anticipatory response accounted for 20%
      49%. Weak responders' (n=4) anticipatory response accounted for 6-20%. Finally,
      non-responders (n=7) showed no anticipatory response. Although previously noted
      anecdotally in the literature, the current study is the first to demonstrate that
      measurable anticipatory sweating occurs prior to fluid intake in dehydrated
      subjects in a significant percentage of the population. Such data suggests that
      cerebral input, like oropharyngeal stimulation, can temporarily remove the
      dehydration-induced inhibition of sweating.

PMID- 22461957
TI  - Rat model of food-induced non-obese-type 2 diabetes mellitus: comparative
      pathophysiology and histopathology.
AB  - Based on the hypothesis that consistent hyperglycemia can result in insulin
      resistance, we explored the induction of non-insulin dependent diabetes mellitus
      (NIDDM) using diet of high glycemic/low fat index and compared the effects on the
      physiology and histology of the rats. The rats were divided into 3 groups. DM was
      induced in the first group by single intraperitoneal injection of 150mg/kg
      alloxan monohydrate and in the second group by feeding the rats with diet of high
      glycemic index/low fat for 8 weeks. The pathophysiology and histopathology of DM
      were studied. Hyperglycemia was recorded in the alloxan and food-induced groups
      respectively. Both groups were also positive for glycosuria, which confirmed the
      induction of DM. Concentrations of plasma potassium, calcium, protein and urea
      were higher (p<0.05) in the alloxan-induced than the food-induced diabetic rats,
      whereas food-induced rats recorded higher hematological indices than the alloxan
      induced group. Coronary risk indices were higher in food-induced diabetic rats
      than the alloxan-induced, while activities of antioxidant enzymes were
      significantly higher (p<0.05) in alloxan-induced diabetic rats than the food
      induced rats. Marked degenerations of the Islets of Langerhans was observed in
      pancreas of alloxan-induced diabetic rats, whereas, histological examination of
      the pancreas of food-induced and control rats revealed no visible lesion. Liver
      and kidney of all food and alloxan-induced diabetic rats showed marked
      degeneration of the hepatocytes and the glomeruli respectively. This study
      presents a rat model of type II diabetes mellitus using food of high glycemic/low
      fat index with its consequent ionoregulatory disruptions, acute anemia,
      hyperlipidemia, nephropathy and hepatopathy.

PMID- 22461958
TI  - Effects of Sexual Expectancies on Early Sexualized Behavior Among Urban Minority
      Youth.
AB  - This study examines the effects of different types of sexual expectancies on
      early sexual behavior among racial/ethnic minority young adolescents. African
      American and Latino participants between 11 and 13 years old were recruited
      through schools and community-based agencies in the South Bronx, New York (N =
      223). Multiple logistic regression analyses were used to predict early sexual
      behavior outcomes, which include engagement in sexual possibility situations,
      kissing, and sexual touching. The moderating effect of gender was examined using
      multiplicative interaction terms. Higher expectations categorized as
      personal/parental and romantic/peer expectancies related to the negative
      consequences of sexual intercourse decreased the odds of engagement in early
      sexual behavior; whereas higher academic/career and sexual health expectancies
      did not. Gender moderated the relationships between personal/parental
      expectancies and engagement in sexual possibility situations and romantic/peer
      expectancies and kissing. Social workers formulating sexual health promotion and
      HIV prevention programs for racial/ethnic minority young adolescents should focus
      on personal/parental and romantic/peer expectancies in favor of negative
      expectancies regarding academic/career achievement, pregnancy, and HIV. Social
      work interventions to delay sexual debut should include a family-based component
      and should be sensitive to gender differences in sexual expectancies.

PMID- 22461959
TI  - Outcomes of birmingham hip resurfacing: a systematic review.
AB  - PURPOSE: We performed a systematic review to assess the functional outcomes of
      Birmingham Hip Resurfacing as reported in peer-reviewed literature. METHODS: We
      performed a computerized search on the data sources up to February 2011. The
      following text and key words were searched: "Birmingham hip", "Birmingham hip
      resurfacing" and "Hip resurfacing". Each of these key words was again searched
      with "outcomes" following them. We also hand searched the bibliographies of the
      retrieved articles and our own files to identify specifically relevant articles.
      RESULTS: Fourteen retrospective studies and three prospective studies were
      included for review. Each of these studies was evaluated by the criteria given by
      Sackett and AACPDM. The design, patient criteria, intervention, outcomes,
      duration of follow up and results of the research were reported. CONCLUSIONS:
      Although the technique of BHR does allow the femur to be spared, claims that it
      may allow patients to be more active need to be further investigated.

PMID- 22461960
TI  - Intrarater reliability of pain intensity, tissue blood flow, thermal pain
      threshold, pressure pain threshold and lumbo-pelvic stability tests in subjects
      with low back pain.
AB  - PURPOSE: This preliminary study aimed to determine the intrarater reliability of
      the quantitative tests for the study of non-specific low back pain. METHODS: Test
      retest reliability of the measurements of ratio data was determined by an
      intraclass correlation coefficient (ICC), standard error of measurements (SEMs),
      coefficient of variation (CV), and one-way repeated measures ANOVA using the
      values collected from 13 young individuals (25.8 +/- 6.2 years) with chronic non
      specific low back pain on two occasions separated by 2 days. Percent agreement of
      the ordinal data was also determined by Cohen's Kappa statistics (kappa). The
      measures consisted of tissue blood flow (BF), average pain visual analog scales
      (VAS), pressure pain threshold (PPT), cold pain threshold (CPT), heat pain
      threshold (HPT) and lumbo-pelvic stability test (LPST). An acceptable reliability
      was determined as the ICC values of greater than 0.85, SEMs less than 5%, CV less
      than 15%, the kappa scores of greater than 80% and no evidence of systematic
      error (ANOVA, P>0.05). RESULTS: ICC of all measures in the lumbo-sacral area were
      greater than 0.87. The kappa was also greater than 83%. Most measures
      demonstrated a minimal error of measurements and less potential of systemic error
      in nature. Only the SEMs and the CV of the CPT exceeded the acceptable level.
      CONCLUSIONS: It is concluded that most of the quantitative measurements are
      reliable for the study of non-specific low back pain, however the CPT should be
      applied with care as it has a great variation among individuals and potential of
      measurement error.

PMID- 22461961
TI  - The effect of sleep deprivation on choice reaction time and anaerobic power of
      college student athletes.
AB  - PURPOSE: The aim of this study was to determine the effect of one night's sleep
      deprivation on anaerobic performance and Reaction time of subjects in the morning
      of the following day. METHODS: Eighteen male college student athletes were
      studied twice in a balanced, randomized design. Subjects were measured for peak
      power, mean power and Reaction time. RESULTS: The performance showed no
      significant difference in both tests of anaerobic power (peak power, mean power)
      over the sleep deprivation period (P= 0.3; P= 0.4 respectively), but reaction
      time differed significantly from baseline (P=0.003). Results support the
      hypothesis that sleep serves a function of cognitive restitution, particularly in
      the maintenance of attentional mechanisms. In the light of the above
      considerations. CONCLUSIONS: It was concluded that short-term sleep deprivation
      is not effective on anaerobic performance, but adversely affects cognitive
      function such as Reaction Time.

PMID- 22461962
TI  - The effect of a combined high-intensity plyometric and speed training program on
      the running and jumping ability of male handball players.
AB  - PURPOSE: The aim of this study was to investigate the effect of a combined
      program including sprint repetitions and drop jump training in the same session
      on male handball players. METHODS: Twenty-two male handball players aged more
      than 20 years were assigned into 2 groups: experimental group (n=11) and control
      group (n=11). Selection was based on variables "axis" and "lines", goalkeepers
      were not included. The experimental group was subjected to 2 testing periods
      (test and retest) separated by 12 weeks of an additional combined plyometric and
      running speed training program. The control group performed the usual handball
      training. The testing period comprised, at the first day, a medical checking,
      anthropometric measurements and an incremental exercise test called yo-yo
      intermittent recovery test. 2 days later, participants performed the Repeated
      Sprint Ability test (RSA), and performed the Jumping Performance using 3
      different events: Squat jump (SJ), Countermovement jump without (CMJ) and with
      arms (CMJA), and Drop jump (DJ). At the end of the training period, participants
      performed again the repeated sprint ability test, and the jumping performance.
      RESULTS: The conventional combined program improved the explosive force ability
      of handball players in CMJ (P=0.01), CMJA (P=0.01) and DJR (P=0.03). The change
      was 2.78, 2.42 and 2.62% respectively. No significant changes were noted in
      performances of the experimental group at the squat jump test and the drop jump
      with the left leg test. The training intervention also improved the running speed
      ability of the experimental group (P=0.003). No statistical differences were
      observed between lines or axes. CONCLUSION: Additional combined training program
      between sprint repetition and vertical jump in the same training session
      positively influence the jumping ability and the sprint ability of handball
      players.

PMID- 22461963
TI  - Role of biofeedback in optimizing psychomotor performance in sports.
AB  - PURPOSE: Biofeedback is an emerging tool to acquire and facilitate physiological
      and psychological domains of the human body like response time and concentration.
      Thus, the present study aims at determining the reconstitution of psychomotor and
      performance skills in basketball players through biofeedback training. METHODS:
      Basketball players (N=30) with different levels of expertise (university, state
      and national) aged 18-28 years (both male and female) were randomly divided into
      3 equal groups - Experimental group, Placebo group and Control group. The
      experimental group received Heart Rate Variability Biofeedback training for 10
      consecutive days for 20 minutes that included breathing at individual's resonant
      frequency through a pacing stimulus; Placebo group was shown motivational video
      clips for 10 consecutive days for 10 minutes, whereas Control group was not given
      any intervention. At session 1, 10 and 1month follow up, heart rate variability,
      respiration rate, response time (reaction and movement time), concentration and
      shooting performance were assessed. RESULTS: Two way repeated measure ANOVA was
      used to simultaneously compare within and between group differences. Response
      time, concentration, heart rate variability, respiration rate and shooting
      differences were statistically significant in each group along with interaction
      of group and time (P<0.001). Also, all the measures showed statistically
      significant inter group difference (P<0.05). CONCLUSION: The results of the study
      suggest that biofeedback training may help to train stressed athletes to acquire
      a control over their psychophysiological processes, thus helping an athlete to
      perform maximally.

PMID- 22461964
TI  - The effect of exercise on urinary gamma-glutamyltransferase and protein levels in
      elite female karate athletes.
AB  - PURPOSE: Post exercise proteinuria and increased urinary Gamma-Glutamyl
      transferase (GGT) levels can be indicative of exercise-induced renal damage. The
      aim of this investigation is to study the effect of one session of intensive
      training on renal damage markers and compare their values to those 6 hours after
      training. METHODS: In this cross-sectional study with pre- and post-test design,
      10 elite volunteer female athletes were selected and participated in one training
      session (2 hours). Urine samples were collected before training, one hour after
      training, and 6 hours after training. Urinary protein (Pr), creatinine (Cr), and
      GGT values were measured through laboratory methods and then Pr/Cr and GGT/Cr
      ratios were computed. RESULTS: There were significant differences between values
      of protein, GGT and Creatinine in the three sampling phases (P<0.05). However, no
      significant differences were observed between values for GGT/Cr and Pr/Cr ratio.
      There were significant differences between the mean values of Creatinine, protein
      and GGT within pre-exercise and 1 hour post-exercise and within 1 hour post
      exercise and 6 hours post-exercise (P<0.05). CONCLUSION: It seems that a session
      of karate training does not result in renal damage and athletes can continue
      training after 6 hours.

PMID- 22461965
TI  - Comparison of MR images for age determination; T1 weighted images (T1WI) versus
      T2* weighted images (T2*WI).
AB  - PURPOSE: T1WI (T1 weighted image) was acquired in order to grade bone fusion
      following the studies by FIFA (Federation Internationale de Football
      Associations). Research using images other than T1WI has not been reported. The
      aim of this study is to evaluate the grade of epiphyseal fusion by T2* weighted
      images (T2*WI) and to investigate new findings on T2*WI as compared with T1WI.
      METHODS: A total of 87 subjects, all junior football players between the ages of
      12 and 17 years old, were examined. T1 and T2* WI were obtained using a 1.2T Open
      type MR system. The T1WI and T2*WI were rated twice randomly by four radiologists
      using the FIFA grading system. RESULTS: The intra-rater reliability for grading
      was higher in T1WI (The Intraclass Correlation Coefficient (ICC)=0.949-0.985)
      than in T2*WI (ICC=0.917-0.943). The inter-rater reliability for grading was also
      higher in T1WI (ICC=0.923) than in T2*WI (ICC=0.867). CONCLUSIONS: This research
      showed that T1WI is a better sequence than T2*WI to evaluate bone fusion
      following FIFA protocol. It was speculated that the reason for this is that T1WI
      has higher tissue contrast resolution and enables clearer images of the
      epiphyseal fusion than T2*WI and the grading system by T1WI was not suitable for
      T2*WI.

PMID- 22461967
TI  - Dog Bites among Off-Road Cyclists: A Report of Two Cases.
AB  - BACKGROUND: As the field of off-road cycling is usually remote areas with limited
      access to medical care, off-road cyclists are at higher risk of animal attacks
      and related injuries. CASE PRESENTATION: We report two cases of dog attacks in
      off-road cycling and discuss the basic principles in prevention and management of
      such incidents. The cyclists received all 5-dose regimen of the rabies vaccine
      and returned to sport after 6 weeks. During 6-month follow-up period, no
      complications were observed. CONCLUSIONS: To reduce the probability of dog
      attacks and its complications, the off-road cyclists should be familiar with some
      basic principles. They should also be educated about initial on-site management
      of the related injuries, which may have a great impact on decreasing further
      complications.

PMID- 22461966
TI  - Bone Mineral Changes and Cardiovascular Effects among Female Athletes with
      Chronic Menstrual Dysfunction.
AB  - PURPOSE: Oligo/amenorrhea, as a part of the Female Athlete Triad has adverse
      effects on the athlete's bone mineral density (BMD) and cardiovascular system.
      Hypoestrogenism, due to suppression of hypothalamus-pituitary axis (HPA) as a
      result of energy imbalance, is the possible cause of the Triad. This study was
      designed based on following up and reassessment of elite female athletes who were
      diagnosed as menstrual dysfunction about two years ago. METHODS: THIS STUDY WAS
      CONDUCTED IN THREE PHASE SECTIONS: 1) Reassess the pattern of menstrual cycle
      among athletes who reported menstrual dysfunction about two years ago; 2) Bone
      mineral density was measured twice in the same machine and same center with a two
      year interval; 3) The laboratory data including blood glucose, lipid profile and
      inflammatory markers was assessed in phase 3. RESULTS: BMD of athletes did not
      change significantly after 25.5 months of oligomenorrhea P (spine) = 0.2, P
      (femur)=0.9. Mean of all cardiovascular factors was in the normal range except
      for high density lipoprotein (HDL) which was 49.28 (SD=9.18), however, most of
      the athletes had abnormalities in their lipid profile. Inverse relationship
      between the increase in the BMD of spine and total cholesterol (r =-0.49,
      P=0.04), Apolipoprotein A (r = -0.51 P=0.04), and very low density lipoprotein
      (VLDL) (r =-0.66, P=0.009). Also correlation between BMD of spine and HbA1C (r =
      0.70, P=0.003) were significant. CONCLUSION: Findings of this study show that
      negative changes in BMD and cardiovascular biomarkers of female athletes with
      functional hypothalamic menstrual dysfunction could occur if proper therapeutic
      intervention (including increase in calorie intake, decrease in exercise load or
      hormonal replacement) will not consider.

PMID- 22461968
TI  - Children dental trauma facts for emergent field management.

PMID- 22461969
TI  - Consultations with general practitioners on patient safety measures based on
      routinely collected data in primary care.
AB  - OBJECTIVES: To gauge the opinions of doctors working, or interested, in general
      practice on monitoring patient safety using administrative data. The findings
      will inform the development of routinely collected data-based patient safety
      indicators in general practice and elsewhere in primary care. DESIGN: Non
      systematic participant recruitment, using personal contacts and colleagues'
      recommendations. SETTING: Face-to-face consultations at participants' places of
      work, between June 2010 and February 2011. PARTICIPANTS: Four general
      practitioners (GPs) and a final year medical student. The four clinicians had
      between eight to 34 years of clinical practice experience, and held non-clinical
      positions in addition to their clinical roles. MAIN OUTCOME MEASURES: Views on
      safety issues and improvement priorities, measurement methods, uses of
      administrative data, role of administrative data in patient safety and
      experiences of quality and safety initiatives. RESULTS: Medication and
      communication were the most commonly identified areas of patient safety concern.
      Perceived safety barriers included incident-reporting reluctance, inadequate
      medical education and low computer competency. Data access, financial
      constraints, policy changes and technology handicaps posed challenges to data
      use. Suggested safety improvements included better communication between
      providers and local partnerships between GPs. CONCLUSIONS: The views of GPs and
      other primary care staff are pivotal to decisions on the future of English
      primary care and the health system. Broad views of general practice safety issues
      were shown, with possible reasons for patient harm and quality and safety
      improvement obstacles. There was general consensus on areas requiring urgent
      attention and strategies to enhance data use for safety monitoring.

PMID- 22461970
TI  - Detection of hidden structures for arbitrary scales in complex physical systems.
AB  - Recent decades have experienced the discovery of numerous complex materials. At
      the root of the complexity underlying many of these materials lies a large number
      of contending atomic- and largerscale configurations. In order to obtain a more
      detailed understanding of such systems, we need tools that enable the detection
      of pertinent structures on all spatial and temporal scales. Towards this end, we
      suggest a new method that applies to both static and dynamic systems which
      invokes ideas from network analysis and information theory. Our approach
      efficiently identifies basic unit cells, topological defects, and candidate
      natural structures. The method is particularly useful where a clear definition of
      order is lacking, and the identified features may constitute a natural point of
      departure for further analysis.

PMID- 22461971
TI  - Competition among memes in a world with limited attention.
AB  - The wide adoption of social media has increased the competition among ideas for
      our finite attention. We employ a parsimonious agent-based model to study whether
      such a competition may affect the popularity of different memes, the diversity of
      information we are exposed to, and the fading of our collective interests for
      specific topics. Agents share messages on a social network but can only pay
      attention to a portion of the information they receive. In the emerging dynamics
      of information diffusion, a few memes go viral while most do not. The predictions
      of our model are consistent with empirical data from Twitter, a popular
      microblogging platform. Surprisingly, we can explain the massive heterogeneity in
      the popularity and persistence of memes as deriving from a combination of the
      competition for our limited attention and the structure of the social network,
      without the need to assume different intrinsic values among ideas.

PMID- 22461972
TI  - A broadly cross-reactive monoclonal antibody against an epitope on the n-terminus
      of meningococcal fHbp.
AB  - Meningococcal factor H binding protein (fHbp) is an important vaccine antigen for
      prevention of disease caused by capsular group B strains. The protein has been
      sub-classified into three variant groups. Most anti-fHbp antibodies are variant
      group-specific and recognize epitopes on the C-terminal domain. We report a
      murine IgG1 mAb, JAR 41, which broadly cross-reacted with fHbp sequence variants
      from all variant groups. The mAb bound to the surface of live meningococci with
      fHbp from each of the three variant groups. In combination with second non
      bactericidal anti-fHbp mAbs, JAR 41 elicited complement-mediated bactericidal
      activity in vitro, and augmented passive protection against meningococcal
      bacteremia in human fH transgenic rats. The epitope was located on a conserved
      region of the N-terminal portion of the fHbp molecule opposite that of fH contact
      residues. The data underscore the importance of broadly cross-reactive, surface
      exposed epitopes on the N-terminal domain in the design of protective fHbp
      vaccines.

PMID- 22461973
TI  - Detecting early-warning signals for sudden deterioration of complex diseases by
      dynamical network biomarkers.
AB  - Considerable evidence suggests that during the progression of complex diseases,
      the deteriorations are not necessarily smooth but are abrupt, and may cause a
      critical transition from one state to another at a tipping point. Here, we
      develop a model-free method to detect early-warning signals of such critical
      transitions, even with only a small number of samples. Specifically, we
      theoretically derive an index based on a dynamical network biomarker (DNB) that
      serves as a general early-warning signal indicating an imminent bifurcation or
      sudden deterioration before the critical transition occurs. Based on theoretical
      analyses, we show that predicting a sudden transition from small samples is
      achievable provided that there are a large number of measurements for each
      sample, e.g., high-throughput data. We employ microarray data of three diseases
      to demonstrate the effectiveness of our method. The relevance of DNBs with the
      diseases was also validated by related experimental data and functional analysis.

PMID- 22461974
TI  - Enhanced gas sensing in pristine carbon nanotubes under continuous ultraviolet
      light illumination.
AB  - The advance of nanomaterials has opened new opportunities to develop ever more
      sensitive sensors owing to their high surface-to-volume ratio. However, it is
      challenging to achieve intrinsic sensitivities of nanomaterials for ultra-low
      level detections due to their vulnerability against contaminations. Here we show
      that despite considerable achievements in the last decade, continuous in situ
      cleaning of carbon nanotubes with ultraviolet light during gas sensing can still
      dramatically enhance their performance. For instance in nitric oxide detection,
      while sensitivity in air is improved two orders of magnitude, under controlled
      environment it reaches a detection limit of 590 parts-per-quadrillion (ppq) at
      room temperature. Furthermore, aiming for practical applications we illustrate
      how to address gas selectivity by introducing a gate bias. The concept of
      continuous in situ cleaning not only reveals the tremendous sensing potential of
      pristine carbon nanotubes but also more importantly it can be applied to other
      nanostructures.

PMID- 22461975
TI  - Pretransplant fasting glucose predicts new-onset diabetes after liver
      transplantation.
AB  - New-onset diabetes after transplantation (NODAT) is common after liver transplant
      and associated with poorer outcomes. The aim of this study was to identify risk
      factors for NODAT in liver transplant recipients off corticosteroids. In 225
      adult nondiabetic liver transplant recipients, the mean age was 51.7 years, the
      majority were men (71%), and half had HCV (49%). The mean calculated MELD score
      at transplantation was 18.7, and 19% underwent living-donor transplant (LDLT).
      One year after transplantation, 17% developed NODAT, and an additional 16% had
      impaired fasting glucose. The incidence of NODAT in patients with HCV was 26%. In
      multivariate analysis, HCV, pretransplant FPG, and LDLT were significant. Each 10
      mg/dL increase in pretransplant FPG was associated with a twofold increase in
      future development of NODAT. The incidence of NODAT after liver transplant in
      patients off corticosteroids is 17%. Risk factors for developing NODAT include
      HCV and pretransplant FPG; LDLT is protective.

PMID- 22461976
TI  - Isolation of human islets for autologous islet transplantation in children and
      adolescents with chronic pancreatitis.
AB  - Chronic pancreatitis is an inflammatory disease of the pancreas that causes
      permanent changes in the function and structure of the pancreas. It is most
      commonly a complication of cystic fibrosis or due to a genetic predisposition.
      Chronic pancreatitis generally presents symptomatically as recurrent abdominal
      pain, which becomes persistent over time. The pain eventually becomes disabling.
      Once specific medical treatments and endoscopic interventions are no longer
      efficacious, total pancreatectomy is the alternative of choice for helping the
      patient achieve pain control. While daily administrations of digestive enzymes
      cannot be avoided, insulin-dependent diabetes can be prevented by transplanting
      the isolated pancreatic islets back to the patient. The greater the number of
      islets infused, the greater the chance to prevent or at least control the effects
      of surgical diabetes. We present here a technical approach for the isolation and
      preservation of the islets proven to be efficient to obtain high numbers of
      islets, favoring the successful treatment of young patients.

PMID- 22461977
TI  - Elevated serum C-reactive protein relates to increased cerebral myoinositol
      levels in middle-aged adults.
AB  - C-reactive protein (CRP), a systemic marker of inflammation, is a risk factor for
      late life cognitive impairment and dementia, yet the mechanisms that link
      elevated CRP to cognitive decline are not fully understood. In this study we
      examined the relationship between CRP and markers of neuronal integrity and
      cerebral metabolism in middle-aged adults with intact cognitive function, using
      proton magnetic resonance spectrocospy. We hypothesized that increased levels of
      circulating CRP would correlate with changes in brain metabolites indicative of
      early brain vulnerability. Thirty-six individuals, aged 40 to 60, underwent
      neuropsychological assessment, a blood draw for CRP quantification, and (1)H MRS
      examining N-acetyl-aspartate, myo-inositol, creatine, choline, and glutamate
      concentrations in occipito-parietal grey matter. Independent of age, sex and
      education, serum CRP was significantly related to higher cerebral myo
      inositol/creatine ratio (F(4,31) = 4.74, P = 0.004), a relationship which
      remained unchanged after adjustment for cardiovascular risk (F(5,30) = 4.356, CRP
      beta = 0.322, P = 0.045). Because these biomarkers are detectable in midlife they
      may serve as useful indicators of brain vulnerability during the preclinical
      period when mitigating intervention is still possible.

PMID- 22461978
TI  - Neuropathology of AIDS: An Autopsy Review of 284 Cases from Brazil Comparing the
      Findings Pre- and Post-HAART (Highly Active Antiretroviral Therapy) and Pre- and
      Postmortem Correlation.
AB  - A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases
      in Brazil (1989-2008) divided into 3 groups: A (without antiretroviral treatment:
      163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months
      or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found,
      predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%)
      followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV
      encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions
      in 1.1%. There was no difference when compared the frequency of lesion among the
      groups; however, toxoplasmosis was less common while HIV encephalitis was more
      frequent in group C related to A. CNS lesions remain a frequent cause of death in
      AIDS; however, the mean survival time was four times greater in group C than in
      A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total
      284 cases), there was discordance between pre- and postmortem diagnosis;
      disagreement type 1 (important disease that if diagnosed in life could change the
      patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the
      total 284) indicating the autopsy importance, even with HAART and advanced
      diagnostics technologies.

PMID- 22461979
TI  - Loss to Followup in HIV-Infected Patients from Asia-Pacific Region: Results from
      TAHOD.
AB  - This study examined characteristics of HIV-infected patients in the TREAT Asia
      HIV Observational Database who were lost to follow-up (LTFU) from treatment and
      care. Time from last clinic visit to 31 March 2009 was analysed to determine the
      interval that best classified LTFU. Patients defined as LTFU were then
      categorised into permanently LTFU (never returned) and temporary LTFU (re-entered
      later), and these groups compared. A total of 3626 patients were included (71%
      male). No clinic visits for 180 days was the best-performing LTFU definition
      (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up,
      1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU
      were younger (P = 0.002), had HIV viral load >=500 copies/mL or missing (P =
      0.021), had shorter history of HIV infection (P = 0.048), and received no, single
      or double-antiretroviral therapy, or a triple-drug regimen containing a protease
      inhibitor (P < 0.001). 48% of patients LTFU never returned. These patients were
      more likely to have low or missing haemoglobin (P < 0.001), missing recent HIV
      viral load (P < 0.001), negative hepatitis C test (P = 0.025), and previous
      temporary LTFU episodes (P < 0.001). Our analyses suggest that patients not seen
      at a clinic for 180 days are at high risk of permanent LTFU, and should be
      aggressively traced.

PMID- 22461980
TI  - Determinants of Adherence to Antiretroviral Therapy among HIV-Infected Patients
      in Africa.
AB  - Background. There are only a few comprehensive studies of adherence to ART and
      its challenges in Africa. This paper aims to assess the evidence on the
      challenges and prospects of ART adherence in sub-Saharan Africa. Methods. The
      authors reviewed original and review articles involving HIV-positive individuals
      that measured adherence to ART and its predictors in the past decade. Findings.
      Against expectations, sub-Saharan Africa patients have similar or higher
      adherence levels compared to those of developed countries. The challenges to ART
      adherence include factors related to patients and their families, socioeconomic
      factors, medication, and healthcare systems. Conclusion. Despite good adherence
      and program-related findings, antiretroviral treatment is challenged by a range
      of hierarchical and interrelated factors. There is substantial room for
      improvement of ART programs in sub-Sahara African countries.

PMID- 22461981
TI  - The use of an early alert system to improve compliance with sepsis bundles and to
      assess impact on mortality.
AB  - Introduction. Diagnostic and therapeutic guidelines, organized as sepsis bundles,
      have been shown to improve mortality, but timely and consistent implementation of
      these can be challenging. Our study examined the use of a screening tool and an
      early alert system to improve bundle compliance and mortality. Methods. A
      screening tool was used to identify patients with severe sepsis or septic shock
      and an overhead alert system known as Code SMART (Sepsis Management Alert
      Response Team) was activated at the physician's discretion. Data was collected
      for 6 months and compliance with bundle completion and mortality were compared
      between the Code SMART and non-Code SMART groups. Results. Fifty eight patients
      were enrolled -34 Code SMART and 24 non-Code SMART. The Code SMART group achieved
      greater compliance with timely antibiotic administration (P < 0.001), lactate
      draw (P < 0.001), and steroid use (P = 0.02). Raw survival and survival adjusted
      for age, leucopenia, and severity of illness scores, were greater in the Code
      SMART group (P < 0.05, P = 0.03, and P = 0.01). Conclusions. A screening tool and
      an alert system can improve compliance with sepsis bundle elements and improve
      survival from severe sepsis and septic shock.

PMID- 22461982
TI  - Longitudinal relationships of religion with posttreatment depression severity in
      older psychiatric patients: evidence of direct and indirect effects.
AB  - Psychiatric patients (age 59+) were assessed before study treatment for major
      depressive disorder, and again after 3 months. Measures taken before study
      treatment included facets of religiousness (subjective religiosity, private
      prayer, worship attendance, and religious media use), social support, and
      perceived stress. Clinician-rated depression severity was assessed both before
      and after treatment using the Montgomery-Asberg Depression Rating Scale (MADRS).
      Structural equation modeling was used to test a path model of direct and indirect
      effects of religious factors via psychosocial pathways. Subjective religiousness
      was directly related to worse initial MADRS, but indirectly related to better
      posttreatment MADRS via the pathway of more private prayer. Worship attendance
      was directly related to better initial MADRS, and indirectly related to better
      post-treatment MADRS via pathways of lower stress, more social support, and more
      private prayer. Private prayer was directly related to better post-treatment
      MADRS. Religious media use was related to more private prayer, but had no direct
      relationship with MADRS.

PMID- 22461983
TI  - Fine structure of glycosaminoglycans from fresh and decellularized porcine
      cardiac valves and pericardium.
AB  - Cardiac valves are dynamic structures, exhibiting a highly specialized
      architecture consisting of cells and extracellular matrix with a relevant
      proteoglycan and glycosaminoglycan content, collagen and elastic fibers.
      Biological valve substitutes are obtained from xenogenic cardiac and pericardial
      tissues. To overcome the limits of such non viable substitutes, tissue
      engineering approaches emerged to create cell repopulated decellularized
      scaffolds. This study was performed to determine the glycosaminoglycans content,
      distribution, and disaccharides composition in porcine aortic and pulmonary
      valves and in pericardium before and after a detergent-based decellularization
      procedure. The fine structural characteristics of galactosaminoglycans
      chondroitin sulfate and dermatan sulfate were examined by FACE. Furthermore, the
      mechanical properties of decellularized pericardium and its propensity to be
      repopulated by in vitro seeded fibroblasts were investigated. Results show that
      galactosaminoglycans and hyaluronan are differently distributed between
      pericardium and valves and within heart valves themselves before and after
      decellularization. The distribution of glycosaminoglycans is also dependent from
      the vascular district and topographic localization. The decellularization
      protocol adopted resulted in a relevant but not selective depletion of
      galactosaminoglycans. As a whole, data suggest that both decellularized porcine
      heart valves and bovine pericardium represent promising materials bearing the
      potential for future development of tissue engineered heart valve scaffolds.

PMID- 22461984
TI  - Triple-negative breast cancer: an update on neoadjuvant clinical trials.
AB  - Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor
      prognosis despite the high rates of response to chemotherapy. This scenario
      highlights the need to develop novel therapies and/or treatment strategies to
      reduce the mortality associated with TNBC. The neoadjuvant setting provides a
      model for rapid assessment of treatment efficacy with smaller patient accruals
      and over shorter periods of time compared to the traditional adjuvant setting. In
      addition, a clear surrogate endpoint of improved survival, known as pathologic
      complete response, already exists in this setting. Here, we review current data
      from completed and ongoing neoadjuvant clinical trials for TNBC.

PMID- 22461985
TI  - Dental Caries, and Supragingival Plaque and Calculus among Students, Tanga,
      Tanzania.
AB  - The prevalence of dental caries and supragingival plaque and calculus in 785
      secondary schools students was assessed. More than half (53.6%) of the students
      were caries-free, and the majority of those with dental caries experience were
      aged 14-17 (68.1%) and females (53%). Mean DMFT was 1.26, with mean D-component
      of 1.05, and molars were most affected. Most students had supragingival plaque
      (74%) and calculus (56.9%) and more so in males than females (P > 0.05). Less
      than half of the students had experience of dental caries and those with caries
      were mostly females and of the younger age group. The low DMFT was contributed to
      the D-component, and molars were the tooth type most affected.The majority of
      students had supra-gingival plaque and calculus and more so in males than
      females.

PMID- 22461986
TI  - A comparison of two pain scales in the assessment of dental pain in East delhi
      children.
AB  - Pain is the most common symptom of oral diseases. Pain perception in children is
      highly variable and unreliable due to poor communication. Therefore we designed a
      study to compare pain measurement techniques, that is, visual analogue scale
      (VAS) and Wong-Baker faces pain rating scale (WBFPS) among Delhi children aged 3
      to 14 years undergoing dental extraction. Method. A cross-sectional study was
      conducted on 180 patients aged 3 to 14 years who had undergone dental extraction.
      Children were assessed for their pain sensitivity using visual analogue scale
      (VAS) and Wong-Baker faces pain rating scale (WBFPS ). Result and Conclusion.
      Pain threshold tends to decline, and the self-management of pain becomes more
      effective with increasing age. Genderwise result shows that communication ability
      of boys and girls is similar in all age groups.

PMID- 22461987
TI  - Assessment of various factors for feasibility of fixed cantilever bridge: a
      review study.
AB  - Cantilever fixed partial dentures are defined as having one or more abutments at
      one end of the prosthesis while the other end is unsupported. Much controversy
      without documentary evidence has surrounded this prosthesis. Despite negative
      arguments, the cantilever prosthesis has been used extensively by the clinicians.
      If used nonjudiciously without following proper guidelines these might lead to
      some complications. Although complications may be an indication that clinical
      failure has occurred, this is not typically the case. It is also possible that
      complications may reflect substandard care. Apart from the substandard care, the
      unique arrangement of the abutments and pontic also accounts for the prime
      disadvantage: the creation of a class I lever system. When the cantilevered
      pontic is placed under occlusal function, forces are placed on the abutments.
      There are various criteria and factors necessary for a successful cantilever
      fixed partial denture (FPD). The purpose of this paper is to discuss briefly
      various factors involved in the planning of a cantilever fixed partial denture.

PMID- 22461988
TI  - In Vitro Antimicrobial Effect of a Cold Plasma Jet against Enterococcus faecalis
      Biofilms.
AB  - The hypothesis that a cold plasma jet has the antimicrobial effect against
      Enterococcus faecalis biofilms was tested in vitro. 27 hydroxyapatite discs were
      incubated with E. faecalis for six days to form a monoculture biofilm on the disc
      surface. The prepared substrata were divided into three groups: the negative
      control, the positive control (5.25% NaOCl solution), and the plasma treatment
      group. Resultant colony-forming unit counts were associated with observations of
      bacterial cell morphology changes using scanning electron microscopy (SEM).
      Treatment of E. faecalis biofilm with the plasma and 5.25% NaOCl for 5 min
      resulted in 93.1% and 90.0% kill (P < 0.0001), respectively. SEM detected that
      nearly no intact bacteria were discernible for the plasma-exposed HA disc
      surfaces. The demonstrated bactericidal effect of the plasma with direct surface
      contact may be due to the enhanced oxidation by the locally produced reactive
      plasma species.

PMID- 22461989
TI  - Occlusal plane determination using custom made broadrick occlusal plane analyser:
      a case control study.
AB  - Proper occlusal plane is an essential consideration when multiple long span
      posterior restorations are designed. The determination of the occlusal plane can
      have a profound effect on the short and long term success of a restorative case.
      Purpose of Study. (1) To determine the appropriate occlusal curve for individual
      patients. (2) To compare the deviation of the clinical occlusal curve with the
      ideal ones. Materials and Methods. A total of 20 subjects were examined and study
      models were made of their maxillary and mandibular dentition. Inter-occlusal
      records were made and the casts were articulated in semiadjustable articulator.
      An ideal occlusal plane was created. The distance of the farthest cusp tip from
      the Broadrick curve was measured along the long axis of the tooth for each
      individual. Paired t-tests were used to compare the findings between subjects and
      controls. Results. A statistically significant difference P < 0.05 was found in
      the deviation from the Broadrick curve between patients who have lost posterior
      teeth and the control group who had a full dentition with no missing teeth.
      Conclusion. Proper utilization of the broadrick flag on a semi-adjustable
      articulator will allow for a correct determination of the occlusal plane.

PMID- 22461990
TI  - Prevalence of first permanent molar caries in and its relationship to the dental
      knowledge of 9-12-year olds from jeddah, kingdom of saudi arabia.
AB  - The carious status of the first permanent molar (FPM) was studied in 432 school
      children (aged 9-12 years) from a randomly selected primary schools from Sharfia
      area of Jeddah, Kingdom of Saudi Arabia. The sample consisted of 108 children
      from each age group of 9, 10, 11, and 12 years old. In total, 24.5% had all of
      their FPMs sound and 6% had all FPMs carious. The prevalence of four sound FPMs
      varied according to age with the highest (33%) amongst the nine-year olds and the
      lowest (16.5%) in the oldest children (12 years). Almost one-third (32.5%) of the
      children, who knew the age of eruption of the FPMs, had all of their molars
      sound. The children who had received advice regarding oral hygiene from a dentist
      or parent had more sound FPMs compared to the children who did not receive any
      advice. The number of carious FPMs increased with age. The prevalence of caries
      of the FPM was high and increased with increasing age. The level of knowledge had
      a positive correlation with the caries levels amongst this cohort of scholars.

PMID- 22461991
TI  - Integrating oral health care into primary health care system.
AB  - Introduction. Systematic evaluation is an integral part of the organization and
      delivery of community oral health care programmes, ensuring the effectiveness of
      these community-based interventions. This study aimed to assess the knowledge and
      practice of primary health care (PHC) personnel regarding their duties toward
      oral health. Methods and Material. A cross-sectional study was carried out among
      three groups of PHC personnel in the city of Kerman (Iran). Volunteer personnel
      completed a piloted questionnaire which included demographic data, some question
      regarding their knowledge about oral health, their duties and also their practice
      regarding public oral health. All data were analyzed using chi-square and Pearson
      correlation test. Results. One hundred and fifty-seven out of 225 eligible
      personnel participated in the study. Sixty percent were auxiliary health workers
      (Behvarz). All personnel had a good level of knowledge regarding oral health.
      Despite significant differences among the knowledge of the personnel toward oral
      health, there was no significant difference between their knowledge related to
      their duties regarding oral health. The auxiliary health worker group had a
      higher rate (45.6%) for better public oral health practice. Conclusion. The study
      showed the personnel have good knowledge of their duties regarding oral health.
      However, their practice is not in line with their knowledge and needs more
      attention.

PMID- 22461992
TI  - Evaluation of Micromovements and Stresses around Single Wide-Diameter and Double
      Implants for Replacing Mandibular Molar: A Three-Dimensional FEA.
AB  - Purpose. The purpose of this finite element study was to compare stresses,
      strains, and displacements of double versus single implant, in immediate loading
      for replacing mandibular molar. Materials and Methods. Two 3D FEM models were
      made to simulate implant designs. The first model used 6 mm wide-diameter implant
      to support a single molar crown. The second model used 3.75-3.75 double implant
      design. Each model was analyzed with a single force magnitude of 70 N in oblique
      axis in three locations. Results. This FEM study suggested that micromotion can
      be well controlled by both double implants and 6 mm single wide-diameter implant.
      The Von Mises stress for double implant had 31%-43% stress reduction compared to
      the 6 mm implant. Conclusion. Within the limitations of the paper, when the
      mesiodistal space for artificial tooth is more than 12.5 mm, under immediate
      loading, the double implant support should be considered.

PMID- 22461993
TI  - Evaluation of PECAM-1 Gene Polymorphism in Patients with Periodontal Disease and
      Healthy Individuals.
AB  - Objective. Our aim in this paper was to investigate the possible genetic
      association between three Ser563Asn, Leu125Val and Arg670Gly polymorphisms of the
      PECAM-1 gene and periodontitis. Methods. Genomic DNA was isolated from whole
      blood of 105 periodontal patient (52 with chronic periodontitis and 53 with
      aggressive periodontitis) and 101 healthy individuals. Samples were genotyped and
      analyzed for the three single-nucleotide polymorphisms (SNPs) of PECAM-1 using
      polymerase chain reaction with sequence-specific primers (PCR-SSPs). Results. A
      statistically significant difference was found between the genotypic distribution
      of the Ser563Asn polymorphism in patients with periodontitis compared to controls
      (P = 0.02). But there were no statistically significant difference between the
      allele frequencies in the different groups (P = 0.05). The other two
      polymorphisms did not show a statistically significant difference in their allele
      and genotype frequencies between the groups. There was no statistically
      significant difference found for any of the polymorphisms allele and genotype
      distribution in aggressive and chronic periodontitis either. Conclusions. No
      significant association was found between the polymorphism tested and the
      subgroups of periodontitis, further research is still necessary to determine
      whether this polymorphism can be used as a genetic marker of periodontitis.

PMID- 22461994
TI  - An in vitro comparative study of intracanal fluid motion and wall shear stress
      induced by ultrasonic and polymer rotary finishing files in a simulated root
      canal model.
AB  - Objective. This in vitro study compared the flow pattern and shear stress of an
      irrigant induced by ultrasonic and polymer rotary finishing file activation in an
      acrylic root canal model. Flow visualization analysis was performed using an
      acrylic canal filled with a mixture of distilled water and rheoscopic fluid. The
      ultrasonic and polymer rotary finishing file were separately tested in the canal
      and activated in a static position and in a cyclical axial motion (up and down).
      Particle movement in the fluid was captured using a high-speed digital camera and
      DaVis 7.1 software. The fluid shear stress analysis was performed using hot film
      anemometry. A hot-wire was placed in an acrylic root canal and the canal was
      filled with distilled water. The ultrasonic and polymer rotary finishing files
      were separately tested in a static position and in a cyclical axial motion.
      Positive needle irrigation was also tested separately for fluid shear stress. The
      induced wall shear stress was measured using LabVIEW 8.0 software.

PMID- 22461995
TI  - Towards universal screening for colon cancer: a cheap, reliable, noninvasive test
      using gene expression analysis of rectal swabs.
AB  - Though colon cancer is the second leading cause of cancer deaths in the US, it is
      entirely preventable through early screening to detect and remove adenomatous
      polyps. Colonoscopy has long been regarded as the "gold standard" but is
      expensive, invasive, and uncomfortable, and only about half those considered at
      risk for colon cancer currently submit to colonoscopy or to less reliable
      alternatives such as fecal occult blood test. Here we describe the use of gene
      expression analysis to detect altered expression of certain genes associated with
      not only colon cancer but also polyps. The analysis can be performed on rectal
      swabs, with specimens provided in a routine doctor's office visit. The existence
      of this cheap and simple test, together with an active program to encourage
      individuals to submit to screening, could help eradicate colon cancer.

PMID- 22461996
TI  - Evaluation of the first commercial hepcidin ELISA for the differential diagnosis
      of anemia of chronic disease and iron deficiency anemia in hospitalized geriatric
      patients.
AB  - Introduction. Anemia is a frequent problem in hospitalized geriatric patients,
      and the anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the
      2 most prevalent causes. The aim of the study was to assess the possible role of
      serum hepcidin in the differential diagnosis between ACD and IDA. Methods. We
      investigated serum hepcidin, iron status, anemia, and C-reactive protein in 39
      consecutive geriatric patients with ACD and IDA. Serum hepcidin levels were
      determined using a commercial ELISA kit (DRG Instruments, Marburg, Germany). We
      also measured hepcidin in 26 healthy controls. Results. The serum hepcidin levels
      were not significantly higher in the 28 patients with ACD as compared to the 11
      patients with IDA. Conclusions. The serum hepcidin levels measured using the
      commercial ELISA kit (DRG) do not appear to increase in older patients with ACD.
      It should be noted that an assay-specific problem could explain our results.

PMID- 22461997
TI  - DIC Score: Statistical Relationship with PT, APTT, and Simplified Scoring Systems
      with Combinations of PT and APTT.
AB  - We looked into the statistical association of prothrombin time (PT) and activated
      partial thromboplastin time (APTT) with disseminated intravascular coagulation
      (DIC) score calculated using the International society for thrombosis and
      haemostasis (ISTH) scoring system. The PT, APTT, PT + APTT, and PT/APTT ratios
      were evaluated against the DIC score by linear regression analysis in fifty
      inpatients with suspected DIC. The PT, PT + APTT, and PT/APTT ratios were all
      found to be statistically significant in predicting DIC scores with P values of
      0.02, 0.03, and 0.02, respectively. The APTT alone was not found to be
      statistically significant in predicting DIC score and had a P value of 0.09. This
      scoring system does not need d-dimer levels and the platelet count.

PMID- 22462000
TI  - Innate Immunity in Lobsters: Partial Purification and Characterization of a
      Panulirus cygnus Anti-A Lectin.
AB  - A lectin detected in haemolymph from the Australian spiny lobster Panulirus
      cygnus agglutinated human ABO Group A cells to a higher titre than Group O or B.
      The lectin also agglutinated rat and sheep erythrocytes, with reactivity with rat
      erythrocytes strongly enhanced by treatment with the proteolytic enzyme papain,
      an observation consistent with reactivity via a glycolipid. The lectin, purified
      by affinity chromatography on fixed rat-erythrocyte stroma, was inhibited equally
      by N-acetylglucosamine and N-acetylgalactosamine. Comparison of data from gel
      filtration of haemolymph (behaving as a 1,800,000 Da macromolecule), and
      polyacrylamide gel electrophoresis of purified lectin (a single 67,000 Da band),
      suggested that in haemolymph the lecin was a multimer. The purified anti-A lectin
      autoprecipitated unless the storage solution contained chaotropic inhibitors (125
      mmol/L sucrose: 500 mmol/L urea). The properties of this anti-A lectin and other
      similar lectins are consistent with a role in innate immunity in these
      invertebrates.

PMID- 22461999
TI  - Inhibition of LPS-Induced Activation of Coagulation by p38 MAPK Inhibitor.
AB  - During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like
      receptor (TLR) 4 and induces complex responses of immune system and coagulation.
      However, the underlying LPS signalling mechanism on coagulation activation
      remains complex. To determine the role of the intracellular signalling factors
      p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-kappaB),
      and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS,
      coagulation process of human whole blood exposed to specific inhibitors was
      measured by thrombelastography. Samples were stimulated with LPS (100 MUg/mL)
      after preincubation with BAY117082 (specific NF-kappaB inhibitor), SP600125
      (specific JNK inhibitor), SB203580 (specific p38 MAPK inhibitor), or vehicle.
      SB203580 strongly inhibited LPS-induced coagulation activation, whereas BAY117082
      and SP600125 showed no significant effect. Activation of p38 MAPK, NF-kappaB, and
      JNK and respective inhibitory effects were confirmed by Multi-Target Sandwich
      ELISA. In conclusion, activation of p38 MAPK is crucial for early LPS-induced
      activation of coagulation.

PMID- 22462001
TI  - Anencephaly: do the pregnancy and maternal characteristics impact the pregnancy
      outcome?
AB  - Objective. To describe the characteristics of obstetric and perinatal outcome of
      a group of pregnancies complicated by an anencephalic fetus. Methods.
      Observational study including anencephalic fetuses, divided into groups according
      to the evolution of pregnancy: elective termination of pregnancy ETP; stillbirths
      (SBs); live births (LBs), and loss of follow-up. After a univariate description
      of the sample, some variables were compared using statistical tests. Results. 180
      anencephalic fetuses were included. The mean maternal age was 25.3 years. In 71
      fetuses (39%) were found additional anomalies. Comparing the groups, no
      statistical differences in maternal age (P = 0.5315), parity (P = 0.6070), number
      of previous abortion (P = 0.7464), fetal sex (P = 0.0502) and additional
      anomalies (P = 0.186) were found. Among those fetuses whose parents opted for
      continuation of pregnancy (n = 53), 20 spontaneous intrauterine deaths occurred
      (38%) and 33 were live births (62%). The average postnatal survival time was 51
      minutes. There was no association between survival time and gestational age (P =
      0.6125) or the presence of additional malformations (P = 0.1948). Conclusion.
      Results presented here could contribute to a better understanding of the natural
      history of this malformation, allowing obstetricians a more detailed discussion
      with the families.

PMID- 22461998
TI  - Regulation of immune responses by histone deacetylase inhibitors.
AB  - Both genetic and epigenetic factors are important regulators of the immune
      system. There is an increasing body of evidence attesting to epigenetic
      modifications that influence the development of distinct innate and adaptive
      immune response cells. Chromatin remodelling via acetylation, methylation,
      phosphorylation, and ubiquitination of histone proteins as well as DNA,
      methylation is epigenetic mechanisms by which immune gene expression can be
      controlled. In this paper, we will discuss the role of epigenetics in the
      regulation of host immunity, with particular emphasis on histone deacetylase
      inhibitors. In particular, the role of HDAC inhibitors as a new class of
      immunomodulatory therapeutics will also be reviewed.

PMID- 22462002
TI  - Interleukin 10 and tumor necrosis factor-alpha in pregnancy: aspects of interest
      in clinical obstetrics.
AB  - The purpose of this study was to review the literature regarding the action of
      the cytokines interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha)
      in pregnancy and to emphasize the factors that are of interest to clinical
      obstetrics. The literature highlights several actions of IL-10 and TNF-alpha
      during pregnancy. The actions of these cytokines seem to be antagonistic and
      dependent on the balance between them, which is orchestrated by the specific
      immunosuppressive action of IL-10. TNF-alpha has a characteristic inflammatory
      action, and it is an additional diabetogenic factor in pregnancy. The loss of the
      control of the production of these cytokines, with increase of TNF-alpha, is
      related to the risk for developing obstetric complications, particularly
      recurrent fetal loss, gestational diabetes mellitus, hypertensive syndromes, and
      fetal growth restriction. However, study results are controversial and are not
      clearly defined. These issues are attributed to the heterogeneity of the studies,
      particularly regarding their sample sizes and sources, the evaluation methods,
      and the multiplicity of factors and conditions that influence cytokine
      production. These questions are fundamental and should be addressed in future
      investigations to obtain more consistent results that can be applied to obstetric
      practice.

PMID- 22462003
TI  - The Diagnostic Properties of Medical History in the Diagnosis of Tubal Pathology
      among Subfertile Patients.
AB  - Objectives. To evaluate the diagnostic performance of medical history in the
      diagnosis of tubal pathology among subfertile patients. Patients and Methods.
      Prospective cross-sectional study was performed. Prior to tubal evaluation,
      medical history data were collected. Sensitivity, specificity, and likelihood
      ratios (LRs) for predicting tubal pathology as determined by laparoscopy and dye
      test were calculated for each issue of medical history. Results. 39.6 % (59/149)
      were diagnosed with tubal pathology. The sensitivity for the different issues
      ranged between 1.7 and 54.2% and the specificity between 75.6 and 97.8%. The
      estimated highest value of positive LR is attributed to the history of ectopic
      pregnancy and lowest of negative LR to pelvic inflammatory disease (PID) and
      abdominal surgery. Conclusion. The positive history of PID, sexually transmitted
      diseases (STDs), abdominal and laparoscopic surgery, and ectopic pregnancy are
      satisfactory screening tests for ruling the tubal pathology in. The negative
      history of evaluated issues is inappropriate for ruling the tubal damage out.

PMID- 22462004
TI  - The evolution of methotrexate as a treatment for ectopic pregnancy and
      gestational trophoblastic neoplasia: a review.
AB  - Methotrexate was developed in 1949 as a synthetic folic acid analogue to compete
      with folic acid and thus interfere with cell replication. While initially
      developed as a potential treatment for acute lymphoblastic leukaemia, a
      serendipitous observation led to methotrexate's use to effect the dramatic cure
      of a case of advanced choriocarcinoma. This prompted the exploration for the
      potential of methotrexate to treat other conditions involving disordered
      trophoblastic tissue. Methotrexate has subsequently revolutionized the treatment
      of two pregnancy-related conditions-gestational trophoblastic neoplasia and
      ectopic pregnancy. This article reviews the development of modern treatment
      protocols that use methotrexate to medically treat these two important
      gynaecological conditions.

PMID- 22462005
TI  - Flow-mediated vasodilation is not attenuated in hypertensive pregnancies despite
      biochemical signs of inflammation.
AB  - Background. Our objective was to evaluate endothelial function and markers of
      inflammation during and after pregnancy in normal pregnancies compared to
      pregnancies complicated with hypertension or preeclampsia (PE). Methods and
      Results. We measured endothelium-dependent brachial artery flow-mediated
      vasodilation (FMD) and high sensitive C-reactive protein (hsCRP), interleukin-6
      (IL-6), and tumour necrosis factor-alpha (TNF-alpha) in 32 women with normal
      pregnancy and in 28 women whose pregnancy was complicated with hypertensive
      disorder in the second half of pregnancy and minimum 3-month postpartum.
      Enhancement of endothelial function was greater in hypertensive than normal
      pregnancies, the mean FMD% being 11.0% versus 8.8% during pregnancy (P = 0.194)
      and 8.0% versus 7.9% postpartum (P = 0.978). Concentrations of markers of
      inflammation were markedly increased in pregnant hypertensive group compared to
      those after delivery (hsCRP 4.5 versus 0.80 mg/L, P = 0.023, IL-6 2.1 versus 1.2
      pg/mL, P = 0.006; TNF-alpha 1.9 versus 1.5 pg/mL, P = 0.030). There were no
      statistically significant associations between the markers of inflammation and
      FMD. Conclusions. Brachial artery FMD was not attenuated in the third trimester
      hypertensive pregnancies compared to normal pregnancies, whereas circulating
      concentrations of hsCRP and IL-6 and TNF-alpha reacted to hypertensive
      complications.

PMID- 22462006
TI  - Fertility preservation in female cancer patients.
AB  - With improved survival rates among cancer patients, fertility preservation is now
      being recognized as an issue of great importance. There are currently several
      methods of fertility preservation available in female cancer patients and the
      options and techniques via assisted reproduction and cryopreservation are
      increasing, but some are still experimental and continues to be evaluated. The
      established means of preserving fertility include embryo cryopreservation,
      gonadal shielding during radiation therapy, ovarian transposition, conservative
      gynecologic surgery such as radical trachelectomy, donor embryos/oocytes,
      gestational surrogacy, and adoption. The experimental methods include oocyte
      cryopreservation, ovarian cryopreservation and transplantation, in vitro
      maturation, and ovarian suppression. With advances in methods for the
      preservation of fertility, providing information about risk of infertility and
      possible options of fertility preservation to all young patients with cancer, and
      discussing future fertility with them should be also considered as one of the
      important parts of consultation at the time of cancer diagnosis.

PMID- 22462007
TI  - A retrospective analysis of transfusion management for obstetric hemorrhage in a
      Japanese obstetric center.
AB  - Background. Since cryoprecipitate, fibrinogen concentrate, or recombinant
      activated factor VII is not approved by public medical insurance in Japan, we
      retrospectively assessed blood product usage in patients with obstetric
      hemorrhage at our tertiary obstetric center. Material and Methods. 220 patients
      with obstetric hemorrhagic disorders who underwent blood product transfusion in
      our institution during a 5-year period were reviewed for the types and volumes of
      blood products transfused. Results. There was a significant positive correlation
      (P< 0.001) between the volume of RCC (red blood cell concentrate) transfused and
      that of FFP (fresh frozen plasma), irrespective of underlying obstetric
      disorders. The median of FFP to RCC ratio in each patient was 1.3-1.4, when 6 or
      more units of RCC were transfused. Conclusions. In transfusion for massive
      obstetric hemorrhage in terms of appropriate supplementation of coagulation
      factors, the transfusion of RCC : FFP = 1 : 1.3-1.4 may be desirable.

PMID- 22462008
TI  - Genesis of preeclampsia: an epidemiological approach.
AB  - THERE ARE ANALYZED SOME OF THE MAIN ASPECTS RELATED TO THE CAUSALITY OF
      PREECLAMPSIA, PRIVILEGING TWO TYPES OF MODELS: the clinic model and the
      epidemiologic model, first one represented by the hypothesis of the reduced
      placental perfusion and the second one considering the epidemiologic findings
      related to the high levels of psychosocial stress and its association with
      preeclampsia. It is reasoned out the relevance of raising the causality of the
      disease from an interdisciplinary perspective, integrating the valuable
      information generated from both types, clinical and epidemiologic, and finally a
      tentative explanatory model of preeclampsia is proposed, the subclinical and
      sociocultural aspects that predispose and trigger the disease are emphasized
      making aspects to stand out: the importance of reduced placental perfusion as an
      indicator of individual risk, and the high levels of physiological stress, as a
      result of the unfavorable conditions of the psychosocial surroundings (indicator
      of population risk) of the pregnant women.

PMID- 22462009
TI  - New concepts in median nail dystrophy, onychomycosis, and hand, foot, and mouth
      disease nail pathology.
AB  - Nails are underutilized as diagnostic tools, despite being involved in many
      dermatologic conditions. This paper explores new concepts in the treatment of
      median nail dystrophy (MND), onychomycosis, and the nail pathology of hand, foot,
      and mouth disease (HFMD). A Pubmed database literature search was conducted for
      MND treatment, onychomycosis treatment, and HFMD nail pathology. Only papers
      published after January 2008 were reviewed. The results showed that 0.1%
      tacrolimus ointment can be an effective treatment for MND. Early studies on laser
      therapy indicate that it is a safe and efficacious treatment option for
      onychomycosis, compared to conventional oral antifungal agents. Vicks VapoRub
      (The Proctor & Gamble Company, Cincinnati, OH) is effective against onychomycosis
      and is a reasonable option in patients who choose to forgo conventional
      treatments. Lastly, there is evidence to support a correlation between HFMD and
      onychomadesis.

PMID- 22462010
TI  - A comparative analysis of mast cell quantification in five common dermatoses:
      lichen simplex chronicus, psoriasis, lichen planus, lupus, and insect
      bite/allergic contact dermatitis/nummular dermatitis.
AB  - There is a large body of literature demonstrating an important role of mast cells
      in adaptive and innate immunity. The distribution of mast cells in the skin
      varies in different parts of the body. It is well known that mast cells are
      important for effector functions of classic IgE-associated allergic disorders as
      well as in host defense against infective agents and influence the manifestation
      of autoimmune diseases. We aimed to quantify mast cells in five common dermatoses
      and compare them statistically with respect to the immunostains. We retrieved
      paraffin-embedded tissue sections from the archives of the Pathology Department
      at the UF, Jacksonville, for five cases with each of the above diagnosis from the
      last three years. We performed CD-117 and tolidine blue stains on each one of
      them. The presence or absence of mast cells was evaluated and quantified. We
      observed that, in the skin, mast cells are mainly located close to the vessels,
      smooth muscle cells, hair follicles, and nerve ending. Our study showed that the
      mast cell distribution pattern is different across the two methods of staining
      for the five aforesaid dermatoses. The other important observation was the
      dendritic morphology of the mast cells.

PMID- 22462012
TI  - Goiter and laryngopharyngeal reflux.
AB  - The purpose of this study is to look at the prevalence of laryngopharyngeal
      reflux disease in patients with goiter in a group of 52 patients with goiter. All
      participants were asked to respond to the 9 questions on the Reflux Symptom Index
      (RSI). A diagnosis of LPRD based on symptoms was made for any RSI score above 10.
      The average score of every question was computed for all patients with goiter and
      compared to the corresponding average score of the controls. A P value of less
      than 0.05 was considered statistically significant. The total prevalence of LPRD
      in patients with goiter as indicated by an RSI score greater than 10 was 15.4%
      versus 9.1% in controls. The difference was not statistically significant (P
      value 0.525). Looking at the average score of the individual symptoms as listed
      in the RSI questionnaire, the average score of all the symptoms was higher in
      patients with goiter versus controls. There was no correlation between LPRD and
      any of the demographic variables except for nodules (P value 0.035). The presence
      of laryngopharyngeal symptoms in patients with goiter should alert the treating
      physician to the presence of laryngopharyngeal reflux disease.

PMID- 22462011
TI  - The malnutrition of obesity: micronutrient deficiencies that promote diabetes.
AB  - Obesity and diabetes are increasing in prevalence worldwide. Despite excessive
      dietary consumption, obese individuals have high rates of micronutrient
      deficiencies. Deficiencies of specific vitamins and minerals that play important
      roles in glucose metabolism and insulin signaling pathways may contribute to the
      development of diabetes in the obese population. This paper reviews the current
      evidence supporting this hypothesis.

PMID- 22462013
TI  - Do surgical interventions influence psychosexual and cosmetic outcomes in women
      with disorders of sex development?
AB  - Clinical practice developed to promote psychosexual well-being in DSD is under
      scrutiny. Although techniques for genital surgery have much improved lately, long
      term studies on psychosexual functioning and cosmetic outcome on which to base
      treatment and counseling are scarce. We studied 91 women with a DSD. Feminizing
      surgery was performed in 64% of the women; in 60% of them, resurgery in puberty
      was needed after a single-stage procedure. Both patients and gynecologists were
      satisfied with the cosmetic appearance of the genitalia. However, forty percent
      of these females experienced sexuality-related distress and 66% was at risk for
      developing a sexual dysfunction, whether they had surgery or not. Recognizing the
      difficulty of accurate assessment, our data indicate that feminizing surgery does
      not seem to improve nor hamper psychosexual outcome, especially in patients with
      severe virilization.

PMID- 22462014
TI  - Activation of biodefense system by low-dose irradiation or radon inhalation and
      its applicable possibility for treatment of diabetes and hepatopathy.
AB  - Adequate oxygen stress induced by low-dose irradiation activates biodefense
      system, such as induction of the synthesis of superoxide dismutase (SOD) and
      glutathione peroxidase. We studied the possibility for alleviation of oxidative
      damage, such as diabetes and nonalcoholic liver disease. Results show that low
      dose gamma-irradiation increases SOD activity and protects against alloxan
      diabetes. Prior or post-low-dose X- or gamma-irradiation increases antioxidative
      functions in livers and inhibits ferric nitrilotriacetate and carbon
      tetrachloride-induced (CCl(4)) hepatopathy. Moreover, radon inhalation also
      inhibits CCl(4)-induced hepatopathy. It is highly possible that low-dose
      irradiation including radon inhalation activates the biodefence systems and,
      therefore, contributes to preventing or reducing reactive oxygen species-related
      diabetes and nonalcoholic liver disease, which are thought to involve
      peroxidation.

PMID- 22462015
TI  - Phenotype and metabolic disorders in polycystic ovary syndrome.
AB  - The polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathies
      in women. Its incidence is assessed at 6-8% of the female population in the
      reproductive age. It is characterised by oligomenorrhea (Oligo), hyperandrogenism
      (HA), and the presence of polycystic ovaries (PCOs). Carbohydrate and lipid
      metabolism is being disturbed in many women with PCOS. The pathogenesis of PCOS
      is still unexplained. Following the main criteria of diagnosis (Rotterdam
      Consensus 2003), Dewailly, Welt and Pehlivanov divided the patients with PCOS
      into 4 phenotype groups: A, B, C, and D. In our studies of 93 patients with PCOS,
      we found (1) the most frequent appearance (60,2%) of the phenotype A [Oligo + HA
      + PCO]; (2) an increased androstenedione concentration in a group with HA (A, B,
      C); (3) an increased HOMA-beta and insulin concentration after 30 min an oral 75
      g glucose tolerance test (OGTT) in a group of obese women with BMI > 30 kg/m(2);
      (4) high levels of total testosterone, total cholesterol, and LDL cholesterol
      concentrations in a group A with classic phenotype of PCOS: Oligo + HA + PCO
      increasing the risk of development of cardiovascular diseases, type 2 diabetes,
      or metabolic syndrome. The average androstenedione concentrations could be a good
      diagnostic and prognostic parameter.

PMID- 22462016
TI  - The influence of incretin mimetics on cardiovascular risk factors in diabetes.
AB  - The authors discuss the strategy of use of incretin hormones in type 2 diabetes
      treatment in the context of cardiovascular complications. The results of the
      phase III study on human GLP-1 (Glucagon-like peptide-1) analogue-liraglutide
      have been presented under common acronym LEAD (Liraglutide-Effect and Action In
      Diabetes). The liraglutide therapy improved glycemic control with low
      hypoglycemia risk and decreased glycated hemoglobin by an average 1,13%.
      Decreases in systolic pressure and significant body weight loss were observed.
      Not only did the index describing beta cells function HOMA-B improve but also did
      the ratio of insulin to proinsulin. Summing up, incretin hormones beneficially
      influence blood glucose level, moreover, their use decreases blood pressure and
      body weight which might indicate their positive influence on cardiovascular
      system in diabetic patients.

PMID- 22462017
TI  - Radioactive iodine therapy decreases recurrence in thyroid papillary
      microcarcinoma.
AB  - Background. The most appropriate therapy for papillary microcarcinoma (PMC) is
      controversial. Methods. We reviewed the therapy and outcome of 407 patients with
      PMC. Results. Three hundred-eighty patients underwent total thyroidectomy, and
      349 patients received I-131 therapy. The median followup was 5.3 years. Forty
      patients developed recurrent disease. On univariate analysis, development of
      disease recurrence was correlated with histological tumor size > 0.8 cm (P =
      0.0104), age < 45 years (P = 0.043), and no I-131 therapy (P < 0.0001). On
      multivariate analysis, histological tumor size > 0.8 cm, positive lymph nodes,
      and no I-131 therapy were significant. The 5-year RFS for patients treated with I
      131 was 95.0% versus 78.6% (P < 0.0001) for patients not treated with I-131.
      Patients with lymph node metastasis who did not receive I-131 had a 5-year RFS of
      42.9% versus 93.2% (P < 0.0001) for patients who received I-131. Conclusions.
      Recommend I-131 remnant ablation for patients with PMC, particularly patients
      with lymph node metastasis.

PMID- 22462018
TI  - Predicting acute ischaemic stroke outcome using clinical and temporal thresholds.
AB  - Background. Few studies have analysed the natural course of cerebral ischaemia
      for predicting outcome. We aimed to determine the early clinical findings and the
      thresholds for deficit severity and symptom duration that make it possible to
      stratify outcome. Methods. We included 154 patients with transient ischaemic
      attack or ischaemic stroke. Stroke profiles and neurological status were assessed
      from onset to 24 hrs, on admission, at 48 hrs, and at discharge. Outcomes were
      evaluated using the modified Rankin Scale. Positive and negative predictive
      values were calculated for the different thresholds. The model was subsequently
      evaluated on a new prospective cohort of 157 patients. Results. Initial National
      Institute of Health Stroke Scale (NIHSS) score <5 and symptoms regressing within
      135 min were predictive of good outcome. Initial NIHSS score >22 and symptom
      stability after 1,230 min were predictive of physical dependency or death.
      Conclusions. Low and high NIHSS cut-off points are effective positive predictive
      values for good and poor outcomes. Thresholds for symptom duration are less
      conclusive.

PMID- 22462020
TI  - Polyetheretherketone cages alone with allograft for three-level anterior cervical
      fusion.
AB  - A total of 25 consecutive patients suffering from degenerative cervical disc
      disease who underwent three-level anterior cervical discectomy and fusion (ACDF)
      including polyetheretherketone (PEEK) cages packed with allograft were followed
      up for at least two years. The fusion rate reached 72% (18/25), and asymptomatic
      pseudarthrosis was seen in 6 patients but without mobility on flexion-extension
      radiographs, and revision surgery was not needed. Cage subsidence occurred at one
      level (C67), but it was not progressive, and reoperation was not necessary. A
      significant increase (P < 0.001) in fused segment angle (FSA) and fused segment
      height (FSH) was observed postoperatively. Similarly, a significant clinical
      improvement (P < 0.001) was demonstrated postoperatively in terms of Japanese
      Orthopedic Association (JOA) score and visual analog scales (VASs) score. PEEK
      cages alone with allograft proved to be a safe and effective surgical option in
      the treatment of three-level degenerative cervical disc disease. Although the
      fusion rate was not high, this technique may offer improvement of symptomatology
      and maintenance of cervical spine's sagittal profile.

PMID- 22462019
TI  - Effect of chronic L-dopa or melatonin treatments after dopamine deafferentation
      in rats: dyskinesia, motor performance, and cytological analysis.
AB  - The present study examines the ability of melatonin to protect striatal
      dopaminergic loss induced by 6-OHDA in a rat model of Parkinson's disease,
      comparing the results with L-DOPA-treated rats. The drugs were administered
      orally daily for a month, their therapeutic or dyskinetic effects were assessed
      by means of abnormal involuntary movements (AIMs) and stepping ability. At the
      cellular level, the response was evaluated using tyrosine hydroxylase
      immunoreactivity and striatal ultrastructural changes to compare between L-DOPA
      induced AIMs and Melatonin-treated rats. Our findings demonstrated that chronic
      oral administration of Melatonin improved the alterations caused by the
      neurotoxin 6-OHDA. Melatonin-treated animals perform better in the motor tasks
      and had no dyskinetic alterations compared to L-DOPA-treated group. At the
      cellular level, we found that Melatonin-treated rats showed more TH-positive
      neurons and their striatal ultrastructure was well preserved. Thus, Melatonin is
      a useful treatment to delay the cellular and behavioral alterations observed in
      Parkinson's disease.

PMID- 22462021
TI  - Glioblastoma multiforme: novel therapeutic approaches.
AB  - The current therapy for glioblastoma multiforme involves total surgical resection
      followed by combination of radiation therapy and temozolomide. Unfortunately, the
      efficacy for such current therapy is limited, and newer approaches are sorely
      needed to treat this deadly disease. We have recently described the isolation of
      bacterial proteins and peptides with anticancer activity. In phase I human
      clinical trials, one such peptide, p28, derived from a bacterial protein azurin,
      showed partial and complete regression of tumors in several patients among 15
      advanced-stage cancer patients with refractory metastatic tumors where the tumors
      were no longer responsive to current conventional drugs. An azurin-like protein
      called Laz derived from Neisseria meningitides demonstrates efficient entry and
      high cytotoxicity towards glioblastoma cells. Laz differs from azurin in having
      an additional 39-amino-acid peptide called an H.8 epitope, which allows entry and
      high cytotoxicity towards glioblastoma cells. Since p28 has been shown to have
      very little toxicity and high anti-tumor activity in advanced-stage cancer
      patients, it will be worthwhile to explore the use of H.8-p28, H.8-azurin, and
      Laz in toxicity studies and glioblastoma therapy in preclinical and human
      clinical trials.

PMID- 22462022
TI  - Perceived impact of spasticity is associated with spatial and temporal parameters
      of gait in multiple sclerosis.
AB  - Background. Spasticity is prevalent and disabling in persons with multiple
      sclerosis (MS), and the development of the Multiple Sclerosis Spasticity Scale-88
      (MSSS-88) provides an opportunity for examining the perceived impact of
      spasticity and its association with gait in this population. Purpose. This study
      examined the association between the perceived impact of spasticity and spatio
      temporal parameters of gait in persons with MS. Methods. The sample included 44
      adults with MS who completed the MSSS-88 and 4 walking trials on a 26-foot
      GAITRite(TM) electronic walkway for measurement of spatio-temporal components of
      gait including velocity, cadence, base of support, step time, single support,
      double support, and swing phase. Results. The overall MSSS-88 score was
      significantly associated with velocity (r = -0.371), cadence (r = -0.306), base
      of support (r = 0.357), step time (r = 0.305), single leg support (r = -0.388),
      double leg support (r = 0.379), and swing phase (r = -0.386). Conclusions. The
      perceived impact of spasticity coincides with alterations of the spatio-temporal
      parameters of gait in MS. This indicates that subsequent interventions might
      target a decrease in spasticity or its perceived impact as an approach for
      improving mobility in MS.

PMID- 22462023
TI  - Interplaying factors that effect multiple sclerosis causation and sustenance.
AB  - The author hypothesized that multiple sclerosis (MS) is a humoral autoimmune
      disease, caused by faulty interplay between myelin-specific, dimeric IgE,
      specifically competing non-IgE antibodies and IgE-triggered degranulating mast
      cells. The principal fault was believed to be insufficient quantity of
      protective, specific non-IgE antibodies. Also conjectured was the possibility of
      an unexpected and adverse immune suppression caused by none-MS pharmaceuticals
      being consumed by patients for their MS or for other conditions. To test both
      hypotheses, a mimotopic, peptide antigen-based, serum immunoassay was developed
      to measure dimer-bound IgE excess among MS patients, wherein the IgE specifically
      complexes with two or more myelin surface epitopes at an interval of 40-100
      Angstroms, a separation critical for mast cell degranulation and cell damaging
      effect. MS test sensitivity and specificity, when analyzing five previously
      untreated patients for dimeric IgE presence, was 100%. In direct comparison,
      twenty age- and gender-matched female and male control subjects were test
      negative. Analysis of 35 multiple sclerosis patients, who were concomitantly
      being treated with potentially immunosuppressive pharmaceuticals, appeared to
      show the substances' negative effect upon MS causation, progression, or specific
      immunoassay performance. Therefore, MS is likely an autoimmune disease caused by
      IgE-mediated mast cell degranulation possibly in conjunction with
      immunosuppressive agents.

PMID- 22462024
TI  - Comparison of the effects of adenosine, inosine, and their combination as an
      adjunct to reperfusion in the treatment of acute myocardial infarction.
AB  - Adenosine and inosine are both key intracellular energy substrates for nucleotide
      synthesis by salvage pathways, especially during ischemic stress conditions.
      Additionally they both possess cell protective and cell repair properties. The
      objective of this study is to detect potential advantages of the combination of
      adenosine and inosine versus each drug alone, in terms of ventricular function,
      infarct size reduction and angiogenesis. Myocardial ischemia was created in
      rodents and treated with adenosine, inosine or their combination. Results of
      experiments showed that the combination of both drugs significantly reduced
      infarct size and improved myocardial angiogenesis and ventricular function. The
      two compounds, while chemically similar, use different intracellular pathways,
      allowing for complementary biological activities without overlapping. The drug
      combination at specific 1 : 5 adenosine : inosine dose ratio demonstrated
      positive cardiologic effects, deserving further evaluation as an adjunct to
      reperfusion techniques during and after acute coronary syndrome. The association
      of adenosine and inosine may contribute to reduce myocardial infarction morbidity
      and mortality rates.

PMID- 22462025
TI  - Distribution of cardiac stem cells in the human heart.
AB  - Introduction. The existence of human cardiac stem cells (hCSC) and their
      regenerative capacity are not fully defined. The aim of this study was to
      identify and analyse the distribution of hCSCs by flow cytometry (FCM). Methods.
      Tissue samples from the left ventricle (LV) and the appendages of the right
      atrium (RA) and left atrium (LA) were taken during cardiac surgery. Mononuclear
      cells (MNCs) were isolated, labelled for the stem-cell-marker c-kit and
      hematopoietic-lineage markers and analysed by FCM. Results. HCSCs could be
      isolated from the RA, LA, and LV without significant quantitative difference
      between both atria (A) (RA 4.80 +/- 1.76% versus LA 4.99 +/- 1.69% of isolated
      MNCs, P = 0.922). The number of hCSCs was significantly higher in both atria
      compared to the left ventricle (A 4.90 +/- 1.29% versus LV 0.62 +/- 0.14% of
      isolated MNCs, P = 0.035). Conclusion. The atria contain a higher concentration
      of hCSC than the left ventricle. HCSCs located in the atria could serve as an
      endogenous source for heart regeneration.

PMID- 22462026
TI  - Stromal-Cell-Derived Factor-1 (SDF-1)/CXCL12 as Potential Target of Therapeutic
      Angiogenesis in Critical Leg Ischaemia.
AB  - In the Western world, peripheral vascular disease (PVD) has a high prevalence
      with high morbidity and mortality. In a large percentage of these patients, lower
      limb amputation is still required. Studies of ischaemic skeletal muscle disclosed
      evidence of endogenous angiogenesis and adaptive skeletal muscle metabolic
      changes in response to hypoxia. Chemokines are potent chemoattractant cytokines
      that regulate leukocyte trafficking in homeostatic and inflammatory processes.
      More than 50 different chemokines and 20 different chemokine receptors have been
      cloned. The chemokine stromal-cell-derived factor-1 (SDF-1 aka CXCL12) is a
      constitutively expressed and inducible chemokine that regulates multiple
      physiological processes, including embryonic development and organ homeostasis.
      The biologic effects of SDF-1 are mediated by chemokine receptor CXCR4, a 352
      amino acid rhodopsin-like transmembrane-specific G protein-coupled receptor
      (GPCR). There is evidence that the administration of SDF-1 increases blood flow
      and perfusion via recruitment of endothelial progenitor cells (EPCs). This review
      will focus on the role of the SDF-1/CXCR4 system in the pathophysiology of PVD
      and discuss their potential as therapeutic targets for PVD.

PMID- 22462027
TI  - Potential of Novel EPO Derivatives in Limb Ischemia.
AB  - Erythropoietin (EPO) has tissue-protective properties, but it increases the risk
      of thromboembolism by raising the haemoglobin concentration. New generation of
      EPO derivatives is tissue protective without the haematopoietic side effects.
      Preclinical studies have demonstrated their effectiveness and safety. This paper
      summarizes the development in EPO derivatives with emphasis on their potential
      use in critical limb ischaemia.

PMID- 22453896
TI  - The buncefield oil depot fire of 2005: potential air-pollution health impacts
      under alternative meteorological scenarios.
AB  - OBJECTIVE: To model the possible air pollution-related health impact of the 2005
      oil depot fire at Buncefield, near London, UK, under alternative meteorological
      conditions to those experienced at the time. DESIGN: Atmospheric dispersion
      modelling of the smoke plume was conducted under the range of meteorological
      conditions occurring throughout 2005 assuming constant particle emission rates.
      Population exposure to particle concentrations (PM10) was calculated by linking
      the atmospheric dispersion modelling data (2 km resolution) and postcode
      population data. Health impacts were estimated using time-series-based exposure
      response relationships for PM10 available from the epidemiological literature.
      MAIN OUTCOMES: Estimates of pollution-related deaths brought forward, emergency
      hospital admissions from respiratory problems and emergency hospital admissions
      from cardiovascular disease. FINDINGS: The highest four-day population exposure
      to PM10 for meteorological data from 2005 was predicted to occur between 5 and 8
      August 2005, when northerly winds would have carried the plume towards London and
      surrounding areas of high population density. On these days, we estimated the
      additional PM10 exposure would have resulted in around 12 extra deaths brought
      forward, and around 13 additional emergency hospital admissions and a similar
      additional number of emergency admissions for cardiovascular disease. These
      numbers are slightly greater than estimated deaths and emergency admissions
      attributable to regular anthropogenic PM10 concentrations in south east England
      over the same four day period. CONCLUSIONS: Although the particle pollution
      related health impacts of the Buncefield fire could have been higher under
      different meteorological conditions, it is unlikely that the impacts would be
      substantially greater than those attributable to regular anthropogenic particle
      pollution over the similar period. KEYWORDS: oil depot fire; health impact;
      epidemiology; air pollution; explosion; atmospheric dispersion modelling;
      exposure.

PMID- 22462028
TI  - The diabetic heart: too sweet for its own good?
AB  - Diabetes mellitus is a major risk factor for ischemic heart disease (IHD).
      Patients with diabetes and IHD experience worse clinical outcomes, suggesting
      that the diabetic heart may be more susceptible to ischemia-reperfusion injury
      (IRI). In contrast, the animal data suggests that the diabetic heart may be
      either more, equally, or even less susceptible to IRI. The conflicting animal
      data may be due to the choice of diabetic and/or IRI animal model. Ischemic
      conditioning, a phenomenon in which the heart is protected against IRI by one or
      more brief nonlethal periods of ischemia and reperfusion, may provide a novel
      cardioprotective strategy for the diabetic heart. Whether the diabetic heart is
      amenable to ischemic conditioning remains to be determined using relevant animal
      models of IRI and/or diabetes. In this paper, we review the limitations of the
      current experimental models used to investigate IRI and cardioprotection in the
      diabetic heart.

PMID- 22453897
TI  - Disasters at mass gatherings: lessons from history.
AB  - IntroductionReviews of mass gathering events have traditionally concentrated on
      crowd variables that affect the level and type of medical care needed. Crowd
      disasters at mass gathering events have not been fully researched and this review
      examines these aiming to provide future suggestions for event organisers, medical
      resource planners, and emergency services, including local hospital emergency
      departments.MethodsA review was conducted using computerised data bases: MEDLINE,
      The Cochrane Library, HMIC and EMBASE, with Google used to widen the search
      beyond peer-reviewed publications, to identify grey literature. All peer-review
      literature articles found containing information pertaining to lessons identified
      from mass gathering crowd disasters were analysed and reviewed. Disasters
      occurring in extreme weather events, and environmental leading to participant
      illness were not included. These articles were read, analysed, abstracted and
      summarised.Results156 articles from literature search were found detailing mass
      gathering disasters identified from 1971 - 2011. With only 21 cases found within
      peer-review literature. Twelve events were further documented as a case reports.
      Five events were examined as review articles while four events underwent
      commissioned inquiries. Analysis of cases were categorised in to crowd control,
      event access, fire safety, medical preparedness and emergency
      response.ConclusionsMass gathering events have an enormous potential to place a
      severe strain on the local health care system, and a mixture of high crowd
      density, restricted points of access, poor fire safety, minimum crowd control and
      lack of on-site medical care can lead to problems that end in disaster.

PMID- 22453898
TI  - Huntington's like conditions in China, A review of published Chinese cases.
AB  - BACKGROUND: Knowledge about HD in China is lacking in the international
      literature. We have therefore analyzed the Chinese literature to thoroughly
      explore the clinical characteristics of Huntington disease in China. METHODS: A
      computer-based online search of China National Knowledge Infrastructure was
      performed to review case reports concerning HD published between January 1980 and
      April of 2011, and the clinical characteristics were extracted. RESULTS: A total
      of 92 studies involving 279 patients (157 males and 122 females) were collected,
      82.0% of which were from provinces of North China. Most of the cases (97.8%) had
      a family history of HD, and paternal inheritance (65.5%) was higher than maternal
      inheritance (34.5%). Onset age was 35.8 (+/- 11.8) years, death occurred with
      45.6 (+/- 13.5) years after a course of 11.6 (+/- 5.6) years. Involuntary
      movements were the most frequent reported presentation (found in 52.3%, including
      64.4% in the entire body, 19.8% in the upper limbs, and 13.7% in the head and
      face). Psychiatric symptoms at onset were reported in 16.1%, and cognitive
      impairment in 1.8%. With disease progression, 99.6% of patients had abnormal
      movements, 67.9% cognitive impairment, and 35.0% suffered psychiatric symptoms.
      Of the reported patients, only 22 underwent IT15 gene testing with positive
      results. CONCLUSION: HD is a well-reported entity in Chinese medical literature,
      however, only a small number of instances have been proven by molecular
      diagnosis. Most of the features resemble what is known in other countries. The
      highly predominant motor presentation, and the higher male prevalence as well as
      the apparent concentration in Northern China may be due to observational bias.
      There is therefore a need to prospectively examine cohorts of patients with
      appropriate comprehensive assessment tools including genetic testing.

PMID- 22453899
TI  - Repression of nuclear CELF activity can rescue CELF-regulated alternative
      splicing defects in skeletal muscle models of myotonic dystrophy.
AB  - Myotonic dystrophy type 1 (DM1) is caused by the expansion of CUG repeats in the
      3' UTR of DMPK transcripts. DM1 pathogenesis has been attributed in part to
      alternative splicing dysregulation via elevation of CUG-BP, Elav-like family
      member 1 (CELF1). Several therapeutic approaches have been tested in cells and
      mice, but no previous studies had specifically targeted CELF1. Here, we show that
      repressing CELF activity rescues CELF-dependent alternative splicing in cell
      culture and transgenic mouse models of DM1. CELF-independent splicing, however,
      remained dysregulated. These data highlight both the potential and limitations of
      targeting CELF1 for the treatment of DM1.

PMID- 22453900
TI  - Quantification of the heat wave effect on mortality in nine French cities during
      summer 2006.
AB  - BACKGROUND: July 2006 was the first major heat wave in France after the creation
      of a heat prevention plan. Understanding its impacts on health will help
      improving the efficiency of this plan. We assessed the mortality impact of the
      heat wave, and investigated the influence of the heat prevention plan. METHODS:
      The study focused on nine French cities. A Poisson regression model was used to
      analyze the correlation between temperature, air quality and mortality. An
      additional spline of time was introduced to capture an additional heat wave
      effect. Heat-action days defined by the prevention plan were introduced as a
      dummy variable. RESULTS: 411 extra deaths were observed in the nine cities during
      the 2006 heat wave. Unlike the 2003 heat wave, no additional heat wave effect was
      observed in 2006. The maximum daily relative risk of mortality varied from 1.45
      in Strasbourg (IC 95% [1.01-2.08]) to 1.04 in Lille (IC 95% [0.92-1.18]). The
      impact on mortality of the implementation of heat-action days was non-significant
      and highly variable depending on the cities, with a combined excess of relative
      risk of -3.3% (IC 95% [-10.3%; 4.4%]). CONCLUSIONS: Although no specific heat
      wave effect was observed, warm temperatures and air pollution were still
      responsible for a significant excess mortality in France. The absence of a
      specific heat wave effect may be partly explained by the prevention plan. It may
      also indicate that higher temperatures are required to observe a mortality
      outburst.

PMID- 22453901
TI  - Standard maximum likelihood analyses of alignments with gaps can be statistically
      inconsistent.
AB  - BackgroundMost statistical methods for phylogenetic estimation in use today treat
      a gap (generally representing an insertion or deletion, i.e., indel) within the
      input sequence alignment as missing data. However, the statistical properties of
      this treatment of indels have not been fully investigated.ResultsWe prove that
      maximum likelihood phylogeny estimation, treating indels as missing data, can be
      statistically inconsistent for a general (and rather simple) model of sequence
      evolution, even when given the true alignment. Therefore, accurate phylogeny
      estimation cannot be guaranteed for maximum likelihood analyses, even given
      arbitrarily long sequences, when indels are present and treated as missing
      data.ConclusionsOur result shows that the standard statistical techniques used to
      estimate phylogenies from sequence alignments may have unfavorable statistical
      properties, even when the sequence alignment is accurate and the assumed
      substitution model matches the generation model. This suggests that the recent
      research focus on developing statistical methods that treat indel events properly
      is an important direction for phylogeny estimation.

PMID- 22453902
TI  - DuchenneConnect Registry Report.
AB  - Research activity in Duchenne/Becker muscular dystrophy has surged in recent
      years, requiring robust information networks to support ongoing development.
      Established by Parent Project Muscular Dystrophy in late 2007, DuchenneConnect
      was created to bridge the information gap between care providers, researchers and
      the patient community, thereby addressing medical care needs and accelerating the
      pace of therapeutic advancements. This report represents the first in a new
      series that will be regularly shared by DuchenneConnect and PPMD. Data in this
      report was collected through June 2011.

PMID- 22453903
TI  - Cholera ante portas - The re-emergence of cholera in Kinshasa after a ten-year
      hiatus.
AB  - BACKGROUND: Cholera is an endemic disease in certain well-defined areas in the
      east of the Democratic Republic of Congo (DRC). The west of the country,
      including the mega-city Kinshasa, has been free of cases since mid 2001 when the
      last outbreak ended. METHODS AND FINDINGS: We used routinely collected passive
      surveillance data to construct epidemic curves of the cholera cases and map the
      spatio-temporal progress of the disease during the first 47 weeks of 2011. We
      compared the spatial distribution of disease spread to that which occurred in the
      last cholera epidemic in Kinshasa between 1996 and 2001. To better understand
      previous determinants of cholera spread in this region, we conducted a
      correlation analysis to assess the impact of rainfall on weekly health zone
      cholera case counts between December 1998 and March 2001 and a Generalized Linear
      Model (GLM) regression analysis to identify factors that have been associated
      with the most vulnerable health zones within Kinshasa between October 1998 and
      June 1999. In February 2011, cholera reemerged in a region surrounding Kisangani
      and gradually spread westwards following the course of the Congo River to
      Kinshasa, home to 10 million people. Ten sampled isolates were confirmed to be
      Vibrio cholerae O1, biotype El Tor, serotype Inaba, resistant to trimethoprim
      sulfa, furazolidone, nalidixic acid, sulfisoxaole, and streptomycin, and
      intermediate resistant to Chloramphenicol. An analysis of a previous outbreak in
      Kinshasa shows that rainfall was correlated with case counts and that health zone
      population densities as well as fishing and trade activities were predictors of
      case counts. CONCLUSION: Cholera is particularly difficult to tackle in the DRC.
      Given the duration of the rainy season and increased riverine traffic from the
      eastern provinces in late 2011, we expect further increases in cholera in the
      coming months and especially within the mega-city Kinshasa. We urge all partners
      involved in the response to remain alert.Didier Bompangue and Silvan Vesenbeckh
      contributed equally to this work. *corresponding author: Silvan Vesenbeckh,
      Harvard School of Public Health (vesenbeckh@gmail.com)Didier Bompangue is
      Associate Professor in the Department of Microbiology (University of Kinshasa)
      andEpidemiologist in the DRC Ministry of Health. He was involved in the
      investigations of the described outbreak since February 2011.

PMID- 22462037
TI  - Bosutinib for the treatment of chronic myeloid leukemia in chronic phase.
AB  - The clinical outcome for patients with chronic myeloid leukemia in chronic phase
      (CML-CP) is currently very favorable due to the availability of tyrosine kinase
      inhibitors (TKIs) that are well tolerated and effectively suppress the
      constitutively activated BCR-ABL1 kinase that underlies the pathogenesis of this
      malignancy. Three TKIs -imatinib, nilotinib and dasatinib- have been approved as
      frontline therapy in CML-CP. Another TKI, bosutinib, inhibits with high potency
      numerous tyrosine kinases, including BCR-ABL1, Src family of kinases and MAPK,
      among others. Like nilotinib and dasatinib, bosutinib is a second-generation TKI
      that inhibits the majority of mutations associated with imatinib resistance, with
      the exception of T315I. In patients with CML-CP with prior intolerance or
      resistance to imatinib therapy, bosutinib rendered response rates similar to
      those observed in the same patient population treated with nilotinib or
      dasatinib. Preliminary results from the ongoing phase III BELA study in which
      bosutinib is compared in a randomized fashion to imatinib for patients with newly
      diagnosed CML-CP have been recently reported. We herein summarize the preclinical
      and clinical experience of bosutinib in CML.

PMID- 22462038
TI  - Eldecalcitol for the treatment of osteoporosis.
AB  - Eldecalcitol [1alpha,25-dihydroxy-2beta-(3-hydroxypropyloxy)-vitamin D3] is an
      analogue of 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], bearing a
      hydroxypropyloxy residue at the 2beta position. Eldecalcitol shows stronger
      effects than alfacalcidol to increase bone mineral density and reduce bone
      resorption markers in osteoporotic patients, and oral once-daily 0.75 MUg
      eldecalcitol reduced vertebral fracture incidence by 26% compared to 1.0 MUg
      alfacalcidol in a 3-year randomized, double-blind, active-comparator clinical
      trial. The effect of eldecalcitol on vertebral fracture incidence was sustained
      throughout the 3-year study period, and the annual incidence of vertebral
      fracture during the third year was significantly lower with eldecalcitol rather
      than with alfacalcidol treatment (3.9% vs 7.0%, respectively). Eldecalcitol also
      reduced the incidence of wrist fractures by 71% compared to alfacalcidol.
      Eldecalcitol is well tolerated and is not associated with serious side effects
      including sustained hypercalcemia. Eldecalcitol was approved for the treatment of
      osteoporosis in Japan in 2011.

PMID- 22462039
TI  - Linaclotide in the management of gastrointestinal tract disorders.
AB  - Chronic constipation is a highly prevalent, heterogeneous disorder that
      significantly affects patients' lives. Nearly 15% of the U.S. population meets
      diagnostic criteria for chronic constipation (1). Chronic constipation reduces
      patients' quality of life and imposes a significant economic burden to the
      healthcare system (2, 3). A number of therapeutic options are currently available
      to treat symptoms of chronic constipation, although they are not universally
      successful (4, 5). Irritable bowel syndrome (IBS) is another common functional
      gastrointestinal disorder, with a prevalence rate estimated at up to 12% in the
      U.S. (6). Similar to chronic constipation, IBS imposes a significant impact on
      both the healthcare system and the individual patient (7-12). Currently, only one
      medication (lubiprostone) is approved by the U.S. Food and Drug Administration
      for the treatment of IBS with constipation (IBS-C), and is approved only for
      women (13). Although effective in many patients, it is not universally effective
      for the treatment of constipation symptoms in all patients with IBS-C. Other
      treatment options are therefore needed for those patients with chronic
      constipation and IBS-C who fail currently available therapies. This article will
      present information on the pharmacology and pharmacokinetics of linaclotide, a
      new agent designed to treat symptoms of both chronic constipation and IBS-C.
      Preclinical data, clinical studies and safety data will also be reviewed.

PMID- 22462040
TI  - Revisiting clonidine: an innovative add-on option for attention
      deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral
      disorder characterized by developmentally inappropriate levels of inattention,
      hyperactivity and impulsivity. Although much evidence supports the use of
      psychostimulants as a first-line treatment in children and adolescents, up to 30%
      of patients may have an inadequate response to these medications. For these
      patients, addition of an alpha2-adrenoceptor agonist can further improve ADHD
      symptoms. The alpha2-adrenoceptor agonists may work in a synergistic fashion with
      stimulants through regulation of prefrontal cortex function. Early studies were
      completed with immediate-release clonidine (CLON-IR), which requires multiple
      daily doses and achieves a higher maximum concentration more rapidly than the
      more recently developed extended-release clonidine (CLON-XR). Pharmacokinetic
      properties of CLON-XR may be responsible for differences in efficacy and
      tolerability between the CLON-IR and CLON-XR formulations. Recent double-blind,
      placebo-controlled trials have shown that extended-release alpha2-adrenoceptor
      agonists are safe and effective, both as monotherapy and as adjunctive treatment
      with stimulants. This review will focus on clonidine used in conjunction with
      stimulants to optimize treatment of ADHD.

PMID- 22462041
TI  - Current status of treatment for chronic hepatitis C virus infection.
AB  - Chronic hepatitis C virus (HCV) infection is responsible for substantial
      mortality and morbidity worldwide. Until recently, the standard of care for the
      treatment of chronic HCV infection had been a combination of pegylated interferon
      (peg-IFN) and ribavirin (RBV). The recent availability of two directly acting
      agents, telaprevir and boceprevir, has led to significantly improved outcomes for
      those patients with HCV genotype 1. Unfortunately, each of these agents must be
      combined with peg-IFN and RBV for optimal efficacy, and substantial treatment
      related toxicity continues to challenge clinicians. However, the drug development
      pipeline for chronic HCV infection is very robust and the emergence of new
      therapies and therapeutic strategies in the near future for managing chronic HCV
      infection is eagerly anticipated.

PMID- 22462042
TI  - A report from the 27th Annual Congress Of The European Association Of Urology
      (February 24-28, 2012 - Paris, France).
AB  - Aging populations worldwide are already increasing the frequency of diseases of
      the urinary tract, including not just malignancies such as prostate and bladder
      cancer, but also common diseases of the aging male, such as benign prostatic
      hyperplasia, as well as age-facilitated diseases of women, such as urinary
      incontinence. Upon this background, the European Association of Urology (EAU)
      2012 congress opened the gates in Paris, with attendees from across Europe and
      beyond crowding the Palais des Congres, as well as the subway lines leading to
      it. Four hectic days of oral and moderated poster sessions began, where leading
      scientists and researchers presented and discussed the results of clinical and
      preclinical research into many areas of urology related with the treatment and
      management of patients. The following report reviews many of these findings
      presented during the meeting, with a most direct impact on the current and future
      treatment for urological diseases.

PMID- 22462043
TI  - Adrenoreactivity of rat pial arteries under conditions of stabilized systemic
      blood pressure.
AB  - Segment-specific characteristics of the reactions of pial arteries of different
      generations to intravenous injection of norepinephrine were studied under
      conditions of instrumental stabilization of systemic blood pressure in rats with
      blocked alpha- and beta-adrenoceptors.

PMID- 22462044
TI  - Effects of 2,4-dimethoxyphenyl biguanide on glutathione system activity in rat
      tissues in brain ischemia-reperfusion.
AB  - We studied the effects of dimethoxyphenyl biguanide on glutathione peroxidase and
      glutathione reductase activities, level of reduced glutathione in rat tissues,
      and activity of some NADPH-regenerating enzymes (glucose-6-phosphate
      dehydrogenase and NADP-isocitrate dehydrogenase) under conditions of ischemia
      reperfusion of the brain. Administration of this biguanide derivative under
      pathological conditions led to a decrease in the analyzed parameters (elevated
      under conditions of ischemia-reperfusion) in the serum and brain tissue. The
      results attest to less pronounced mobilization of the glutathione system
      (compared to pathological state) due to antioxidant and protective properties of
      2,4-dimethoxyphenyl biguanide under conditions of ischemic tissue damage
      associated with oxidative stress.

PMID- 22462045
TI  - Changes in contractile activity of the duodenum, jejunum, and ileum under
      conditions of psychogenic stress in rabbits.
AB  - Psychogenic stress in rabbits caused by fixation of the animal to a frame was
      accompanied by an increase in duodenal contractile activity. In the jejunum,
      initial inhibition of motor activity gave way to activation more pronounced in
      the proximal part. In both parts of the ileum, inhibition of contractile activity
      was noted. A proximodistal gradient of the excitatory and inhibitory effects on
      the motility of the small intestine was demonstrated.

PMID- 22462046
TI  - A comparative study of antioxidant system and intensity of lipid peroxidation in
      type 2 diabetes mellitus and ischemic stroke aggravated and not aggravated by
      type 2 diabetes mellitus.
AB  - The survey was conducted on patients with type 2 diabetes mellitus and on
      patients with ischemic stroke aggravated and not aggravated by type 2 diabetes
      mellitus. A comparative study of the function of antioxidant system and the
      intensity of oxidative stress induced by lipid peroxidation (LPO) in the blood
      was carried out. Stroke aggravated by diabetes was characterized by higher
      intensity of LPO than stroke not aggravated by diabetes, which, apparently,
      determines the more severe course of stroke in patients with diabetes. The
      mechanisms of compensatory response to oxidative stress at the level of
      antioxidants in stroke aggravated by diabetes also differed from those in stroke
      not aggravated by diabetes. These data indicate the need of using water-soluble
      low-molecular-weight antioxidants in the treatment of stroke aggravated by
      diabetes.

PMID- 22462047
TI  - New approaches to molecular diagnostics of prenatal pathology.
AB  - Analysis of the spectrum of amniotic fluid proteins in physiological and abnormal
      pregnancy using proteomic analysis allowed detection of a number of difference
      proteins, that are absent or, alternatively, appear in gestosis. Among absent
      proteins, there were NADPH-dependent carbonyl reductase, epidermal fatty acid
      binding protein, haptoglobin, calgranulins A and B. In contrast to proteomic
      spectrum of amniotic fluid in physiological pregnancy, 7 new proteins appear
      during gestosis, 3 of them were identified: C area of immunoglobulin K-chain,
      breast cancer metastasis suppressor-1, and protein-1 containing AIG2-like domain.
      Possible effects of revealed differences in proteomic spectrum on development of
      main disturbances during gestosis are discussed. Difference proteins detected in
      amniotic fluid may serve as gestosis markers.

PMID- 22462048
TI  - Respiration restitution in rats following its termination in immersion
      hypothermia.
AB  - Rats were cooled in water until attaining profound hypothermia and respiratory
      arrest. After removal from water, 0.5% solution of Na2EDTA was administered
      intravenously. This led to a drop of blood [Ca2+] by 20-30% from the baseline and
      promoted recovery of respiration following its arrest lasting 10.3+/-1.4 min. By
      the 30th minute of Na2EDTA administration, respiration rate increased to 32.3+/
      5.2 cycles per minute and respiration amplitude reached 68+/-4% of the baseline
      level. This effect was observed without special warming of the rats. It was
      concluded that the period during which the organism maintains viability in
      respiration arrest and disturbances in respiratory center are still reversible is
      prolonged under conditions of profound hypothermia.

PMID- 22462049
TI  - Activity of Ca2+-dependent neutral proteases in tissues of ground squirrel during
      hibernation and during self-warming after induced awakening.
AB  - Cyclic changes in activity of Ca2+-dependent neutral protease occur during
      preparation for hibernation, with an increase in September and November and
      decrease in October and December. During hibernation proteolytic enzyme activity
      decreased, while during self-warming after induced awakening, the role of Ca2+
      dependent processes in the tissues of ground squirrels increased according to the
      body temperature.

PMID- 22462050
TI  - Vitamin B-complex initiates growth and development of human embryonic brain cells
      in vitro.
AB  - We studied a combined effect of subcomponents of vitamin B complex on the growth,
      development, and death of human embryonic brain-derived cells (E90) cultured
      using a modified method of Matson. Cell death was detected by trypan blue
      staining. According to our results, vitamin B-complex in low-doses promote the
      development, maturation, and enlargement of human embryonic brain cells, on the
      one hand, and increases the percent of cell death, which attests to accelerated
      maturation and metabolism, on the other.

PMID- 22462051
TI  - Neuroprotective effect of GK-2, a dipeptide mimetic of nerve growth factor,
      during experimental focal ischemia in middle cerebral artery basin.
AB  - Magnetic resonance tomography, staining with triphenyltetrazolium chloride, and
      tests for evaluation of functional disturbances "cylinder" and "limb stimulation"
      showed that daily intraperitoneal injection of dipeptide mimetic of nerve growth
      factor GK-2 (1 mg/kg) for 6 days to rats with experimental focal ischemia
      provoked by unilateral intravascular occlusion of a branch of the middle cerebral
      artery significantly improved neurological deficit and decreased the infarction
      area.

PMID- 22462052
TI  - Modification of sulpiride model of benign prostatic hyperplasia for evaluation of
      the effectiveness of drug therapy.
AB  - Specific effects of ultra-low doses of antibodies to prostate-specific antigen
      obtained from laboratory rats of late reproductive age with sulpiride model of
      benign prostatic hyperplasia were compared with the results of clinical
      application of the preparation. Clinical reproducibility of experimental data was
      proven, which suggests that the developed model is adequate for pilot testing of
      the effects of pharmacotherapy of this disease.

PMID- 22462053
TI  - Effects of afobazole on the content of neurotransmitter amino acids in the
      striatum in global transient ischemia.
AB  - Anxiolytic agent afobazole (10 mg/kg intraperitoneally) 24 h after ischemia
      restores impaired balance of excitatory and inhibitory amino acids in the
      striatum of mongrel rats, normalizes their content to control levels, and
      activates endogenous taurine-dependent system of neuroprotection.

PMID- 22462054
TI  - Glycidipine, a promising hypotensive and cardioprotective agent.
AB  - Toxicological pharmacological study of the molecular complex of nifedipine and
      glycyrrhizic acid 1:10 (glycidipine) obtained using mechanochemical technique was
      carried out. High hypotensive and cardioprotective effects of the agent were
      demonstrated. Chronic administration (45 days) produced no toxic effects in vital
      organs and systems of Wistar rats and ISIAH rats.

PMID- 22462055
TI  - Effects of amikacin on maturation of the auditory analyzer in rabbits.
AB  - We studied the dynamics of maturation of the hearing function by records of short
      term latent brainstem evoked potentials and the effect of amikacin on maturation
      of the hearing function. The peripheral compartment of the auditory analyzer
      matures sooner than the central structures. Amikacin in therapeutic doses
      exhibited an ototoxic effect on the peripheral compartment of the auditory
      analyzer without impairing its central structures.

PMID- 22462056
TI  - Anxiolytic and antidepressant effects of aqueous tincture of the aerial part of
      Myosotis arvensis.
AB  - Experiments on outbred albino mice showed a significant anxiolytic effect of
      aqueous tincture of the aerial part of Myosotis arvensis (L.) (Boraginaceae) in a
      single daily dose of 0.5 ml/kg. In a dose of 2 ml/kg, the tincture of M. arvensis
      aerial part exhibited an anxiolytic and antidepressant effect. In contrast to
      phenazepam, aqueous tincture of M. arvensis did not inhibit exploratory and motor
      activities.

PMID- 22462057
TI  - Effects of immunization with group a streptococcal antigens on the
      transplantability of mouse bone marrow stromal stem cells, counts of stromal
      precursor cells, and their osteogenic characteristics.
AB  - Immunization of CBA mice with killed group A streptococcus (type 5) vaccine
      changed the counts of stromal precursor cells (CFC-F) in bone marrow transplants
      at different donor-recipient combinations (normal, N, or immune, I). CFC-F counts
      in bone marrow transplants from normal mice transplanted to immunized animals
      decreased 4-6-fold depending on the transplant age in comparison with similar
      transplants in normal recipients. The percentage of CFC-F colonies with alkaline
      phosphatase (osteogenesis marker) activity decreased more than 2-fold. Similarly,
      the count of CFC-F in the transplants was 2-fold lower during delayed (7 months)
      period after bone marrow transplantation from immunized donors (8-12 days after
      the end of immunization) to intact recipients, while 2 months after
      transplantation it was 3-fold lower. The mean optical density of the bone capsule
      in preparations stained for glycogen and alkaline phosphatase was 1.5-3 times
      lower in the N-->I and I-->N experiments in comparison with the control (N-->N).
      On the other hand, CFC-F count in the femoral bone marrow of immunized animals
      was significantly (3.5-2.5 times) higher during the period from 8 days to 8
      months after the end of immunization compared to CFC-F count in the femoral bone
      marrow of intact mice. These results attest to a significant prolonged effect of
      streptococcal antigens on the bone marrow stromal tissue. These data also
      indicate that not all CFC-F, the counts of which increased in response to
      antigens, are responsible for transplantability of the stromal tissue in
      heterotopic transplantation. Immunization by streptococcal antigens seemed to
      suppress transplantability and osteogenic activity of stromal stem cells. The
      efficiency of CFC-F cloning in mouse bone marrow cultures increased significantly
      (2-3-fold) in the presence of sera from immune mice. The levels of TNF-alpha and
      IFN-gamma were low in this serum (2.7 and 6 times lower, respectively) in
      comparison with normal serum. Presumably, the effects of streptococcal antigens
      on stromal tissue were mediated through serum cytokines.

PMID- 22462058
TI  - Antiviral activity of Inonotus obliquus fungus extract towards infection caused
      by hepatitis C virus in cell cultures.
AB  - Fractions of Inonotus obliquus fungus water extract exhibited a virucidal effect
      towards hepatitis C virus: it 100-fold reduced its infective properties within 10
      min. The antiviral effects of fungus extracts manifested after preventive (24 h
      before infection) and therapeutic use (during infection of porcine embryo kidney
      cells). Moreover, the data indicate that the birch fungus extracts inhibit
      production of infective virus by porcine embryo kidney cells.

PMID- 22462059
TI  - Detection of new epitopes of antibodies to filaggrin in filaggrin protein
      molecule.
AB  - Immunogenic characteristics of filaggrin protein molecule as an antigen for
      antibodies to filaggrin, markers of early rheumatoid arthritis, were studied. Two
      new peptide motives, possible epitopes for antibodies to filaggrin, were shown in
      the filaggrin molecule by predictive analysis using programmed algorithms. Only
      IMG-3 and its cyclic form IMG-4 exhibited antigenic reactivity with sera from
      rheumatoid arthritis patients, differing significantly from the reactivity with
      donor sera. The immunogenic characteristics of IMG-3 differed from the
      characteristics of a previously described epitope.

PMID- 22462060
TI  - Genetic variability of enterobacterial resistant integrons.
AB  - Sulfamide-resistant (SulR) natural strains of enterobacteria (11.9% of a total of
      797 cultures, isolated with enteric microflora of honeybee gut, bee-fermented
      pollen, and plant issues) were tested for class 1 antibiotic resistance integrons
      (MRI). Only 5.3% of SulR strains were MRI-positive. Mutability of weak (wild
      type) MRI promotor has been shown. A more active hybrid promotor type has been
      amplified in isolated Klebsiella oxytoca strains. Regulatory genetic
      modifications in MRI are fraught with the development of multiple drug resistance
      of opportunistic strains.

PMID- 22462062
TI  - Morphological studies of the metastatic process after LIO-1 tumor transplantation
      by different methods.
AB  - Variants of injection of LIO-1 lymphosarcoma cell suspension were studied. The
      number of animals with local metastases was higher after injection of LIO-1 cell
      suspension into the mouse paw sole. This method of tumor cell injection is
      suggested as the metastasizing model for experimental studies.

PMID- 22462061
TI  - Dynamics of elimination of bacterial endotoxins and cytokines from the blood of
      tumor patients with sepsis in hemoperfusion using carbon adsorbents.
AB  - We studied the effects of carbon adsorbent hemoperfusion on the dynamics of LPS
      and cytokine concentrations in the blood of cancer patients with sepsis and
      septic shock. In addition, hemadsorbent washout fluid specimens after
      hemoperfusion were analyzed. A significant (3-fold) reduction of blood LPS levels
      after hemoperfusion was found, while shifts in free cytokine levels in the sera
      were negligible. At the same time, hemadsorbents used in the study effectively
      eliminated some free cytokines (IL-6, -8, -12, IFN-gamma, TNF-alpha) from the
      blood.

PMID- 22462063
TI  - Functional unity of the thymus and pineal gland and study of the mechanisms of
      aging.
AB  - The data on the morphology and functions of the thymus and pineal gland in
      individuals of different age are analyzed and common mechanisms of involution of
      these organs during aging and the consequencies of this process are discussed.
      Based on the data on the molecular changes in the thymus and pineal gland during
      aging, the authors hypothesize the functional unity of these organs and their
      mutual complementarity in the maintenance of normal immune and endocrine status
      during aging.

PMID- 22462064
TI  - Age-specific dynamics of human thymus immune cell differentiation.
AB  - The expression of markers of undifferentiated CD5+ cells, B cells, T
      killer/suppressors, and T-helpers was verified by immunohistochemical methods in
      the thymuses of elderly, senile, and long-lived humans. The counts of CD5+ cells
      in the thymus progressively decreased with age. Positive correlations between the
      counts of CD5+ cells and differentiated T cells were detected. The capacity of
      CD5+ thymocytes to differentiate into T-killer/suppressors decreased with age.

PMID- 22462065
TI  - Pathomorphology of the heart conduction system: comparative study during increase
      in left or right ventricular afterload.
AB  - Pathomorphology of the peripheral compartments of the heart conduction system
      under conditions of increased left or right ventricular afterload is
      characterized by interstitial edema, hemorrhages, and reversible and irreversible
      focal lesions. The percentage of damaged conduction cardiomyocytes increases in
      the wall of hemodynamically overloaded ventricle and in the ventricular septum.
      These changes are more pronounced in cases when the afterload increase is
      complicated by heart failure development. Acute dilatation of the heart and
      distention of the myocardium are events of great specific significance in the
      genesis of the conduction system disorders developing under conditions of
      increased right ventricular afterload in comparison with those developing under
      conditions of increase left ventricular afterload. These data attest the presence
      of a pathomorphological base for the appearance of arrhythmias during the acute
      phase of pressure overload of the heart, especially in cases when it is
      aggravated by heart failure.

PMID- 22462066
TI  - Infradian fluctuations in serum testosterone levels in male laboratory rats.
AB  - The dynamics of serum testosterone was studied in laboratory male rats kept
      separately from females. Infradian rhythm of changes in testosterone level equal
      to 4 days and ultradian (within 24 h) periods equal to 160 and 480 min were
      detected. The maximum serum level of testosterone in male rats was synchronized
      with the greatest number of estrous females.

PMID- 22462067
TI  - Mouse hepatocytes retain the expression of the main differentiation markers
      during culturing on collagen-chitosan matrices.
AB  - Mouse hepatocytes cultured on artificial 3D collagen-chitosan biopolymer matrices
      retained the expression of hepatocyte markers for 14 days.

PMID- 22462068
TI  - Regeneration potential of transplanted adult mouse sertoli cells.
AB  - The regeneration potential of differentiated Sertoli cells subjected to thermal
      treatment was studied by the method of cell transplantation. Cells from mice with
      artificial cryptorchism (1.5 months after fixation of the testes in the body) and
      after culturing (10 days, 37 degrees C) were transplanted. Transplantation of
      Sertoli cells from 2-3-month-old and 2-day-old mice served as controls. The cells
      were transplanted into the testes of recipient mice, from which sex cells and
      Sertoli cells were removed by busulfan and cadmium salt treatment. Adult mouse
      Sertoli cells exposed to thermal treatment exhibited much higher regeneration
      potential than intact cells. Two months after transplantation, mature Sertoli
      cells subjected to thermal treatment populated the recipient testicular tubules,
      formed new tubules, and in some cases supported the development of sex cells
      similarly as immature cells from newborn mice.

PMID- 22462069
TI  - Morphometric characteristics of placental villi in pregnant women with diabetes.
AB  - We conducted a comparative morphological study of placentas from women with
      gestational diabetes and diabetes mellitus. Morphometry of histological
      preparations revealed similar type of changes in the studied parameters of
      placental villi in diabetes mellitus and gestational diabetes. The maximum
      deviation of the studied parameters from the control was noted in type 1 diabetes
      mellitus.

PMID- 22462070
TI  - A noninvasive method of examination of the hemostasis system.
AB  - We propose a noninvasive method of in vivo examination the hemostasis system
      based on speckle pattern analysis of coherent light scattering from the skin. We
      compared the results of measuring basic blood coagulation parameters by
      conventional invasive and noninvasive methods. A strict correlation was found
      between the results of measurement of soluble fibrin monomer complexes,
      international normalized ratio (INR), prothrombin index, and protein C content.
      The noninvasive method of examination of the hemostatic system enable rough
      evaluation of the intensity of the intravascular coagulation and correction of
      the dose of indirect anticoagulants maintaining desired values of INR or
      prothrombin index.

PMID- 22462071
TI  - Method of assessment of the dynamics of salivary function in rats during the
      experiment.
AB  - The dynamics of salivary function was studied on 80 laboratory rats. It was found
      that construction of a graph showing the dynamics of stimulated salivation in
      small laboratory animals could be successfully used in various studies.

PMID- 22462072
TI  - Study of oxygen effects on electrochemiluminescence using dye-doped oxygen
      resisting nanobeads.
AB  - Tris(4,7-diphenyl-1,10-phenanthroline)-ruthenium(II) (Rudpp) doped oxygen
      resisting nanobeads were synthesized and applied in order to study the effects of
      oxygen on electrochemiluminescence.

PMID- 22462073
TI  - Rapid extraction and quantitative detection of the herbicide diuron in surface
      water by a hapten-functionalized carbon nanotubes based electrochemical analyzer.
AB  - A solid phase extraction micro-cartridge containing a non-polar polystyrene
      absorbent matrix was coupled with an electrochemical immunoassay analyzer (EIA)
      and used for the ultra-sensitive detection of the phenyl urea herbicide diuron in
      real samples. The EIA was fabricated by using carboxylated carbon nanotubes
      (CNTs) functionalized with a hapten molecule (an amine functionalized diuron
      derivative). Screen printed electrodes (SPE) were modified with these haptenized
      CNTs and specific in-house generated anti diuron antibodies were used for bio
      interface development. The immunodetection was realized in a competitive
      electrochemical immunoassay format using alkaline phosphatase labeled secondary
      anti-IgG antibody. The addition of 1-naphthyl phosphate substrate resulted in the
      production of an electrochemically active product, 1-naphthol, which was
      monitored by using differential pulse voltammetry (DPV). The assay exhibited
      excellent sensitivity and specificity having a dynamic response range of 0.01 pg
      mL(-1) to 10 MUg mL(-1) for diuron with a limit of detection of around 0.1 pg mL(
      1) (n = 3) in standard water samples. The micro-cartridge coupled hapten-CNTs
      modified SPE provided an effective and efficient electrochemical immunoassay for
      the real-time monitoring of pesticides samples with a very high degree of
      sensitivity.

PMID- 22462074
TI  - Electrochemical determination of glutathione: a review.
AB  - The physiological importance of glutathione and glutathione disulfide is evident
      from their implications in an array of medical conditions including diabetes,
      Parkinson's disease and cancer. As such the need for simple, rapid and cheap
      assays to aid clinical diagnostics and treatment is clear. These requirements
      are, in principle at least, ideally suited to electrochemical detection.
      Accordingly a large array of voltammetric methods ultimately aimed at making
      cheap and most likely disposable electrodes have been reported. This critical
      review analyses the context in which physiological glutathione measurement can be
      undertaken electrochemically and compares it to current assay approaches, while
      also covering the current literature for glutathione disulfide detection. The
      various characteristics and limitations of the methodologies are compared and
      contrasted, with the analytical parameters (matrix, pH, limit of detection, etc.)
      tabulated to aid comparison.

PMID- 22462075
TI  - Feature article: Treating the untreatable: a breakthrough in understanding the
      biology and treatment of ovarian cancer.

PMID- 22462077
TI  - [Proceedings and abstracts of the Hamburger Hemophilia-Symposium 2010, November
      12-13, 2010, Hamburg, Germany].

PMID- 22462076
TI  - Abstracts of the XXV National Cardiology Congress, the Global Interventional
      Summit-GIS, and the 7th Turkish World Cardiology Congress. October 21-24, 2010,
      Istanbul, Turkey.

PMID- 22462078
TI  - Proceedings of the 9th Keele Meeting on Aluminium, February 19-23, 2011, Ontario,
      Canada.

PMID- 22462079
TI  - [Proceedings and abstracts of the 64th Congress of the French National Society of
      Internal Medicine, December 14-16, 2011, Paris, France].

PMID- 22462080
TI  - Obesity and alcohol misuse.

PMID- 22462081
TI  - New research methodologies and hitherto unexamined issues in autism as well as
      lines of inquiry that have been overlooked of late.

PMID- 22462082
TI  - Reflections: neurology and the humanities. The art of preserving personhood.

PMID- 22462083
TI  - Reflections: Neurology and the humanities. The changing view from Lookout
      Mountain.

PMID- 22462084
TI  - Reflections: neurology and the humanities.  Recognition.

PMID- 22462085
TI  - Reflections: neurology and the humanities.  Floatopia, sarbox, and health care
      reform: the unintended consequences of law.

PMID- 22462086
TI  - New dream team for melanoma therapy.

PMID- 22462087
TI  - US approves Prevnar pneumonia vaccine for adults.

PMID- 22462088
TI  - Exchange perspective: hospitals encourage designs reducing negative effects.

PMID- 22462091
TI  - Top of mind: Looking ahead 2012 unfold key players in the health care industry
      detail their organizations' marketing and communications priorities.

PMID- 22462089
TI  - Back on the agenda: repeal of contentious IPAB moves forward.

PMID- 22462092
TI  - Tap into a forgotten market.

PMID- 22462093
TI  - Uninsured patients require creative discharge plans.
AB  - Case managers are being challenged to find a discharge destination for patients
      who are uninsured or underinsured and who need services after
      hospitalization.These patients often stay in the hospital longer than necessary,
      at the hospital's expense. Case managers should develop a network of community
      resources that can assist with care for unfunded patients after discharge. In
      some cases, it makes sense for the hospital to pay for a lower level of care
      rather than keeping patients in acute care beds that could be occupied by paying
      patients. Case managers often are under pressure to move patients through the
      continuum of care, making it a challenge to create an effective discharge plan
      for patients with limited financial resources. Many unfunded patients are
      eligible for financial assistance with their healthcare needs, but they aren't
      aware of it and don't know how to apply.

PMID- 22462094
TI  - Unfunded patients are on the increase.

PMID- 22462095
TI  - Challenges for post-acute care.
AB  - Hospitals across the country are providing care for undocumented immigrants,
      often at great expense when they need post-acute care. Many have long lengths of
      stay when they can't be safely discharged and don't have funding for another
      level of care. Some may qualify for Medicaid benefits if their Permanently
      Residing Under Color of Law (PRUCOL) application is accepted. In some cases, it
      may be financially advantageous to the hospital to transport the patient back to
      their native countries for care.

PMID- 22462096
TI  - Think like a payer when patients are uninsured.
AB  - Hospitals need to develop a detailed policy of when and how they'll provide post
      acute financial assistance for uninsured or under-insured patients. The policy
      should allow staff to get real time decisions about what will be covered. Staff
      should apply the policy consistently to all patients in all situations. A policy
      frees up case managers to coordinate care for all their patients rather than
      spending hours at a time trying to line up post-acute care for unfunded patients.

PMID- 22462097
TI  - Proactive approach identifies benefits.
AB  - The University of Iowa Hospitals and Clinics in Iowa City, has developed
      strategies to identify uninsured patients early in the stay, and help them access
      ongoing care in the community. Twelve healthcare benefit assistance program
      social workers educate patients and families about financial options and help
      them apply for government-sponsored programs. Through a Revolving Fund agreement,
      the hospital pays the Medicaid rate to post-acute facilities while patients'
      Social Security Disability is pending and is paid back when the disability
      coverage is approved. Dedicated social workers help patients who need brand name
      medications and can't afford them sign up for national pharmaceutical assistance
      programs.

PMID- 22462098
TI  - Dedicated CM coordinates discharges for patients.
AB  - Montefiore Medical Center in Bronx, NY, has a complex case manager who
      coordinates post-discharge options for uninsured patients with complex needs. The
      initiative frees up unit case managers and social workers to manage the care of
      less complex patients. The hospital has an arrangement with a community-based
      organization to provide a safe living environment for patients who are homeless
      and need post-acute services. A complex care advisory team reviews patients with
      post-discharge issues and makes a recommendation to the hospital's
      administration.

PMID- 22462099
TI  - Community joins forces to care for uninsured.
AB  - Faced with a high rate of unemployment and an increase in uninsured patients, Lee
      Memorial Health system in Ft. Myers, FL sponsored a community-wide effort to
      provide health care options for unfunded patients. Triage Center provides post
      acute medical care for the homeless. Salvation Army operates 10-bed respite unit
      that provides skilled nursing services for homeless. Hospital operates free
      clinics for the uninsured.

PMID- 22462100
TI  - Pictorial prostitution: visual culture, vigilantism, and "pornography" in
      Dunton's "Night-walker".

PMID- 22462101
TI  - Persistent complement-dependent anti-AnWj in a lymphoproliferative disorder: a
      case study and review.
AB  - AnWj is a high-incidence antigen present on the red blood cells (RBCs) of greater
      than 99 percent of the general population. A 58-year-old man underwent autologous
      hematopoietic stem cell transplantation (HSCT) for stage IVa mantle cell
      lymphoma. This procedure was complicated by failure to engraft, necessitating
      ongoing support with blood components. After a 2-month period of uneventful
      transfusion support, the patient experienced increasingly severe reactions with
      fever and evidence of intravascular hemolysis, including hemoglobinuria. Testing
      revealed a complement-dependent anti-AnWj. Phenotyping confirmed the AnWj-
      phenotype. Anti-AnWj was persistent despite immunosuppression, including
      treatment with allogeneic HSCT. Of interest, the pathogenesis of the
      downregulation of the graft AnWj in this patient is unclear.

PMID- 22462102
TI  - The Indian blood group system.
AB  - The Indian blood group system (ISBT: IN/023) consists of two antithetical
      antigens: In(a) (IN1), which is present in approximately 10 percent of some Arab
      populations and in 3 percent of Bombay Indians, and its allelic antigen In(b)
      (IN2), an antigen of high incidence in all populations. In 2007, two new high
      incidence antigens were identified as belonging to the IN blood group system,
      namely IN3 (INFI) and IN4 (INJA). The antigens in this system are located on
      CD44, a single-pass membrane glycoprotein that is encoded by the CD44 gene on
      chromosome 11 at position p13. The biologic function of CD44 is as a leukocyte
      homing receptor and cellular adhesion molecule. The In(a) and In(b) polymorphism
      represents a 252G>C substitution of CD44, encoding R46P, and lack of IN3 and IN4
      results from homozygosity for mutations encoding H85Q and T163R in the CD44 gene.
      The high-frequency antigen AnWj (901009) has not been assigned to the Indian
      system, but either is located on an isoform of CD44 or is closely associated with
      it.

PMID- 22462103
TI  - Rare Disease Day, our Roma cousins and the power of one.

PMID- 22462104
TI  - The structure of the nervous system of the nematode Caenorhabditis elegans.
AB  - The structure and connectivity of the nervous system of the nematode
      Caenorhabditis elegans has been deduced from reconstructions of electron
      micrographs of serial sections. The hermaphrodite nervous system has a total
      complement of 302 neurons, which are arranged in an essentially invariant
      structure. Neurons with similar morphologies and connectivities have been grouped
      together into classes; there are 118 such classes. Neurons have simple
      morphologies with few, if any, branches. Processes from neurons run in defined
      positions within bundles of parallel processes, synaptic connections being made
      en passant. Process bundles are arranged longitudinally and circumferentially and
      are often adjacent to ridges of hypodermis. Neurons are generally highly locally
      connected, making synaptic connections with many of their neighbours. Muscle
      cells have arms that run out to process bundles containing motoneuron axons. Here
      they receive their synaptic input in defined regions along the surface of the
      bundles, where motoneuron axons reside. Most of the morphologically identifiable
      synaptic connections in a typical animal are described. These consist of about
      5000 chemical synapses, 2000 neuromuscular junctions and 600 gap junctions.

PMID- 22462105
TI  - Biclustering of gene expression data by an extension of mixtures of factor
      analyzers.
AB  - A challenge in microarray data analysis concerns discovering local structures
      composed by sets of genes that show homogeneous expression patterns across
      subsets of conditions. We present an extension of the mixture of factor analyzers
      model (MFA) allowing for simultaneous clustering of genes and conditions. The
      proposed model is rather flexible since it models the density of high-dimensional
      data assuming a mixture of Gaussian distributions with a particular omponent
      specific covariance structure. Specifically, a binary and row stochastic matrix
      representing tissue membership is used to cluster tissues (experimental
      conditions), whereas the traditional mixture approach is used to define the gene
      clustering. An alternating expectation conditional maximization (AECM) algorithm
      is proposed for parameter estimation; experiments on simulated and real data show
      the efficiency of our method as a general approach to biclustering. The Matlab
      code of the algorithm is available upon request from authors.

PMID- 22462106
TI  - "This theatre of monstrous guilt:" Horace Walpole and the drama of incest.

PMID- 22462107
TI  - Holland's greatest beggar: fundraising and public relations at the Joodsche
      Invalide.

PMID- 22462108
TI  - Circumcision registers as historical sources.

PMID- 22462110
TI  - The Kohla Project: studying the past with the Tamu-mai.

PMID- 22462114
TI  - On the Plackett distribution with bivariate censored data.
AB  - In the analysis of dependence of bivariate correlated failure time data, a
      popular model is a gamma frailty model proposed by Clayton and Oakes. An
      alternative approach is using a Plackett distribution, whose dependence parameter
      has a very appealing odds ratio interpretation for dependence between the two
      failure times. In this article, we develop novel semiparametric estimation and
      inference procedures for the model. The asymptotic results of the estimator are
      developed; in addition, a goodness of fit test is also developed. We also discuss
      a regression extension to adjust for covariates using the linear regression model
      as well as applications to semi-competing risks data. The performance of the
      proposed techniques in finite samples is examined using simulation studies.
      Several real-data examples are used to illustrate the methodology.

PMID- 22462111
TI  - Urbanization, government policies and growing food insecurity in Kathmandu
      metropolis.

PMID- 22462115
TI  - Instrumental variables vs. grouping approach for reducing bias due to measurement
      error.
AB  - Attenuation of the exposure-response relationship due to exposure measurement
      error is often encountered in epidemiology. Given that error cannot be totally
      eliminated, bias correction methods of analysis are needed. Many methods require
      more than one exposure measurement per person to be made, but the 'group mean OLS
      method,' in which subjects are grouped into several a priori defined groups
      followed by ordinary least squares (OLS) regression on the group means, can be
      applied with one measurement. An alternative approach is to use an instrumental
      variable (IV) method in which both the single error-prone measure and an IV are
      used in IV analysis. In this paper we show that the 'group mean OLS' estimator is
      equal to an IV estimator with the group mean used as IV, but that the variance
      estimators for the two methods are different. We derive a simple expression for
      the bias in the common estimator which is a simple function of group size,
      reliability and contrast of exposure between groups, and show that the bias can
      be very small when group size is large. We compare this method with a new
      proposal (group mean ranking method), also applicable with a single exposure
      measurement, in which the IV is the rank of the group means. When there are two
      independent exposure measurements per subject, we propose a new IV method (EVROS
      IV) and compare it with Carroll and Stefanski's (CS IV) proposal in which the
      second measure is used as an IV; the new IV estimator combines aspects of the
      'group mean' and 'CS' strategies. All methods are evaluated in terms of bias,
      precision and root mean square error via simulations and a dataset from
      occupational epidemiology. The 'group mean ranking method' does not offer much
      improvement over the 'group mean method.' Compared with the 'CS' method, the
      'EVROS' method is less affected by low reliability of exposure. We conclude that
      the group IV methods we propose may provide a useful way to handle mismeasured
      exposures in epidemiology with or without replicate measurements. Our finding may
      also have implications for the use of aggregate variables in epidemiology to
      control for unmeasured confounding.

PMID- 22462117
TI  - Sample size estimation for repeated measures analysis in randomized clinical
      trials with missing data.
AB  - In designing longitudinal studies, researchers must determine the number of
      subjects to randomize based on the power to detect a clinically meaningful
      treatment difference and a proposed analysis plan. In this paper, we present
      formulas for sample size estimation and an assessment of statistical power for a
      two-treatment repeated measures design allowing for subject attrition. These
      formulas can be used for comparing two treatment groups across time in terms of
      linear contrasts. Subjects are assumed to drop out of the study at random so that
      the missing data do not alter the parameters of interest.

PMID- 22462118
TI  - Statistical models for assessing agreement in method comparison studies with
      replicate measurements.
AB  - Method comparison studies are usually analyzed by computing limits of agreement.
      It is recommended that replicate measurements be taken by each method, but the
      resulting data are more cumbersome to analyze. We discuss the statistical model
      underlying the classical limits of agreement and extend it to the case with
      replicate measurements. As the required code to fit the models is non-trivial, we
      provide example computer code to fit the models, and show how to use the output
      to derive measures of repeatability and limits of agreement.

PMID- 22462119
TI  - Missing confounding data in marginal structural models: a comparison of inverse
      probability weighting and multiple imputation.
AB  - Standard statistical analyses of observational data often exclude valuable
      information from individuals with incomplete measurements. This may lead to
      biased estimates of the treatment effect and loss of precision. The issue of
      missing data for inverse probability of treatment weighted estimation of marginal
      structural models (MSMs) has often been addressed, though little has been done to
      compare different missing data techniques in this relatively new method of
      analysis. We propose a method for systematically dealing with missingness in MSMs
      by treating missingness as a cause for censoring and weighting subjects by the
      inverse probability of missingness. We developed a series of simulations to
      systematically compare the effect of using case deletion, our inverse weighting
      approach, and multiple imputation in a MSM when there is missing information on
      an important confounder. We found that multiple imputation was slightly less
      biased and considerably less variable than the inverse probability approach.
      Thus, the lower variability achieved through multiple imputation makes it
      desirable in most practical cases where the missing data are strongly predicted
      by the available data. Inverse probability weighting is, however, a superior
      alternative to naive approaches such as complete-case analysis.

PMID- 22462120
TI  - Pattern mixture models and latent class models for the analysis of multivariate
      longitudinal data with informative dropouts.
AB  - Missing data and especially dropouts frequently arise in longitudinal data.
      Maximum likelihood estimates are consistent when data are missing at random (MAR)
      but, as this assumption is not checkable, pattern mixture models (PMM) have been
      developed to deal with informative dropout. More recently, latent class models
      (LCM) have been proposed as a way to relax PMM assumptions. The aim of this paper
      is to compare PMM and LCM in order to tackle informative dropout in a
      longitudinal study of cognitive ageing measured by several psychometric tests.
      Using a multivariate longitudinal model with a latent process, a sensitivity
      analysis was performed to compare estimates under the MAR assumption, from a PMM
      and from two LCM. In the PMM, dropout patterns are included as covariates in the
      multivariate longitudinal model. In the simple LCM, they are predictors of the
      class membership probabilities while, in the joint LCM, the dropout time is
      jointly modeled using a proportional hazard model depending on latent classes. We
      show that parameter interpretation is different in the two kinds of models and
      thus can lead to different estimated values. PMM parameters are adjusted on the
      dropout patterns while LCM parameters are adjusted on the latent classes. This
      difference is highlighted in our data set because the latent classes exhibit much
      more heterogeneity than dropout patterns. We suggest several complementary
      analyses to investigate the characteristics of latent classes in order to
      understand the meaning of the parameters when using LCM to deal with informative
      dropout.

PMID- 22462121
TI  - Direct effect models.
AB  - The causal effect of a treatment on an outcome is generally mediated by several
      intermediate variables. Estimation of the component of the causal effect of a
      treatment that is not mediated by an intermediate variable (the direct effect of
      the treatment) is often relevant to mechanistic understanding and to the design
      of clinical and public health interventions. Robins, Greenland and Pearl develop
      counterfactual definitions for two types of direct effects, natural and
      controlled, and discuss assumptions, beyond those of sequential randomization,
      required for the identifiability of natural direct effects. Building on their
      earlier work and that of others, this article provides an alternative
      counterfactual definition of a natural direct effect, the identifiability of
      which is based only on the assumption of sequential randomization. In addition, a
      novel approach to direct effect estimation is presented, based on assuming a
      model directly on the natural direct effect, possibly conditional on a subset of
      the baseline covariates. Inverse probability of censoring weighted estimators,
      double robust inverse probability of censoring weighted estimators, likelihood
      based estimators, and targeted maximum likelihood-based estimators are proposed
      for the unknown parameters of this novel causal model.

PMID- 22462122
TI  - Splenic marginal zone lymphoma masquerading as cirrhotic hypersplenism for seven
      years.

PMID- 22462123
TI  - Comment: improved local efficiency and double robustness.
AB  - For missing data and causal inference problems, Rubin and van der Laan (2008)
      proposed estimators to achieve so-called improved local efficiency. We show that
      their estimators agree with existing estimators in the case of linear models,
      point out that one particular version of their estimators is also doubly robust,
      and suggest an extension for where the propensity score is estimated.

PMID- 22462124
TI  - Rejoinder to Tan.
AB  - We respond to several interesting points raised by Tan regarding our article.

PMID- 22462125
TI  - [The current status of HIV infection].

PMID- 22462126
TI  - [HIV infection and the mechanism of viral proliferation, with special reference
      to the stage where the antiviral agents exert their effects].

PMID- 22462127
TI  - [HIV infection route].

PMID- 22462128
TI  - [HIV infection and the diagnostic standard for AIDS].

PMID- 22462129
TI  - [Guideline for HIV therapy].

PMID- 22462130
TI  - [Patient support: social support system related to HIV infection].

PMID- 22462131
TI  - [The current status of drug-resistant HIV and its management in Japan].

PMID- 22462132
TI  - [Practice of anti-HIV therapy (HAART)].

PMID- 22462133
TI  - [Features and the method of application of a CCR5 antagonist, a new integrase
      inhibitor].

PMID- 22462135
TI  - [Current status of opportunistic infections associated with HIV infection].

PMID- 22462134
TI  - [Status of anti-HIV drug development and an overview of combined chemotherapy].

PMID- 22462136
TI  - [Double infection of HIV and hepatitis viruses].

PMID- 22462137
TI  - [Overview on research and development of AIDS vaccine].

PMID- 22462138
TI  - [Prevention of spread of HIV infections: from a public health viewpoint].

PMID- 22462139
TI  - [Avoidance of needle punctures and prevention of post-exposure infection].

PMID- 22462140
TI  - [Current status and treatment of opportunistic infections associated with HIV
      infection: discussion].

PMID- 22462141
TI  - [Phytobezoar].

PMID- 22462142
TI  - [Pauchi-immune crescentic glomerulonephritis associated with rheumatoid
      arthritis].

PMID- 22462143
TI  - [Hypoglycemia due to ectopic secretion of insulin-like growth factor-I in a
      patient with an isolated sarcoidosis of the spleen].

PMID- 22462145
TI  - [Regenerative medicine for heart diseases].

PMID- 22462144
TI  - [Type 2 diabetes mellitus with hemoptysis suspiciously caused by infectious
      pulmonary artery aneurysm associated with pneumonia].

PMID- 22462147
TI  - [Guideline for the treatment of atrial fibrillation].

PMID- 22462146
TI  - [Kidney diseases and mineralocorticoid receptor].

PMID- 22462148
TI  - [Compilation of Tokai Section Educational Seminar: Current diagnostic imaging].

PMID- 22462149
TI  - [Clinical quiz: breathlessness and edema in a 77-year-old woman].

PMID- 22462150
TI  - [Diagnosis at a glance].

PMID- 22462151
TI  - [Approach to patients with chest plain to avoid overlooking cases with acute
      coronary syndrome].

PMID- 22462152
TI  - Estimation based on case-control designs with known prevalence probability.
AB  - Regular case-control sampling is an extremely common design used to generate data
      to estimate effects of exposures or treatments on a binary outcome of interest
      when the proportion of cases (i.e., binary outcome equal to 1) in the population
      of interest is low. Case-control sampling represents a biased sample of a target
      population of interest by sampling a disproportional number of cases. Case
      control studies are also commonly employed to estimate the effects of genetic
      markers or biomarkers on binary phenotypes. In this article we present a general
      method of estimation relying on knowing the prevalence probability, conditional
      on the matching variable if matching is used. Our general proposed methodology,
      involving a simple weighting scheme of cases and controls, maps any estimation
      method for a parameter developed for prospective sampling from the population of
      interest into an estimation method based on case-control sampling from this
      population. We show that this case-control weighting of an efficient estimator
      for a prospective sample from the target population of interest maps into an
      efficient estimator for matched and unmatched case-control sampling. In
      particular, we show how application of this generic methodology provides us with
      double robust locally efficient targeted maximum likelihood estimators of the
      causal relative risk and causal odds ratio for regular case control sampling and
      matched case control sampling. Various extensions and generalizations of our
      methods are discussed.

PMID- 22462153
TI  - [Knowledge on kidney diseases necessary for those specializing in comprehensive
      internal medicine].

PMID- 22462154
TI  - [Commentary on the guidelines for clinical evaluation of diagnostic
      radiopharmaceuticals by the Japanese Society of Nuclear Medicine (3). The draft
      of the guidelines by the Japanese Society of Nuclear Medicine].

PMID- 22462155
TI  - [[Practice guidelines for FDG PET, PET/CT].

PMID- 22462156
TI  - [Creation of myocardial single-photon emission computed tomography databases and
      clinical validation].

PMID- 22462157
TI  - [Adverse reactions due to dietary supplements and Chinese herbal drugs].

PMID- 22462158
TI  - [Study of Japanese history of anesthesia--for the prevention of anesthetic
      accidents].

PMID- 22462159
TI  - [Roles of aquaporins in the central nervous system].

PMID- 22462160
TI  - [Development of an endotracheal tube with movable blocker].

PMID- 22462161
TI  - [Intensity-dependent activation of extracellular signal-regulated protein kinases
      (ERK) 5 in sensory neurons contributes to pain hypersensitivity].

PMID- 22462162
TI  - [Cerebral circulation during anesthesia in diabetic patients].

PMID- 22462163
TI  - [Role of serotonin in chronic pain].

PMID- 22462164
TI  - [Cardiovascular control in space: Arterial pressure regulation under
      gravitational stress].

PMID- 22462165
TI  - [Vasopressin as a vasoactive agent: Its intracellular signal mechanism].

PMID- 22462166
TI  - [Identification of hibernation controlling hormone and mechanisms of protecting
      organisms].

PMID- 22462167
TI  - [Anesthesia for spine surgery and neurophysiologic monitoring of the spinal
      cord].

PMID- 22462168
TI  - [How to understand EEG during anesthesia in relation to awareness during
      anesthesia].

PMID- 22462169
TI  - [Pharmacokinetics of local anesthetics: relationships with central nervous system
      toxicity].

PMID- 22462170
TI  - [Systemic toxicity of local anesthetics and its clinical management].

PMID- 22462171
TI  - [Anesthetic management of patients with airway hypersensitivity].

PMID- 22462172
TI  - [Problems related anesthesia for end-stage renal failure].

PMID- 22462173
TI  - [Point in the coaching the anesthesia trainee--how effective is the off-job
      training!].

PMID- 22462174
TI  - [Mechanism in bone cancer pain].

PMID- 22462175
TI  - [Pathophysiology and treatments of cancer pain with treatments of cancer pain
      refractory to opioids].

PMID- 22462176
TI  - [Anesthetic management of children after cardiac surgery].

PMID- 22462177
TI  - [Analysis of ECG from the view of ion channel activation].

PMID- 22462178
TI  - [Perioperative care for patients with coronary artery disease undergoing
      noncardiac surgery].

PMID- 22462179
TI  - [Ultrasound imaging for nerve block in pediatric patients].

PMID- 22462180
TI  - [Techniques and devices for regional anesthesia in children].

PMID- 22462181
TI  - [Proper understanding and pre-use check of your anesthesia machines].

PMID- 22462182
TI  - [Crisis management in anesthesia and technology].

PMID- 22462183
TI  - [Epidural anesthesia and adult obese patients].

PMID- 22462184
TI  - [Anesthetic management of endoscopic surgery in patients with morbid obesity].

PMID- 22462185
TI  - [Patient-controlled analgesia in the management of postoperative pain-intravenous
      PCA].

PMID- 22462186
TI  - [Postoperative pain management under epidural analgesia].

PMID- 22462187
TI  - [The working group on "Witch Trials in the Trier Region"].

PMID- 22462188
TI  - Gifts for the dead: death, kinship and commemoration in Muscovy: the case of the
      Mstislavskii princes.

PMID- 22462190
TI  - Why are recessions good for your health?

PMID- 22462189
TI  - On the bases of ethnic reproduction of the Russian people.

PMID- 22462191
TI  - Families and firms: the culture and evolution of family firms in Britain and
      Italy in the nineteenth and twentieth centuries.

PMID- 22462193
TI  - The draw-down of retirement savings.

PMID- 22462194
TI  - Ontology and medical diagnosis.
AB  - Ontology and associated generic tools are appropriate for knowledge modeling and
      reasoning, but most of the time, disease definitions in existing description
      logic (DL) ontology are not sufficient to classify patient's characteristics
      under a particular disease because they do not formalize operational definitions
      of diseases (association of signs and symptoms=diagnostic criteria). The main
      objective of this study is to propose an ontological representation which takes
      into account the diagnostic criteria on which specific patient conditions may be
      classified under a specific disease. This method needs as a prerequisite a clear
      list of necessary and sufficient diagnostic criteria as defined for lots of
      diseases by learned societies. It does not include probability/uncertainty which
      Web Ontology Language (OWL 2.0) cannot handle. We illustrate it with
      spondyloarthritis (SpA). Ontology has been designed in Protege 4.1 OWL-DL2.0.
      Several kinds of criteria were formalized: (1) mandatory criteria, (2) picking
      two criteria among several diagnostic criteria, (3) numeric criteria. Thirty real
      patient cases were successfully classified with the reasoner. This study shows
      that it is possible to represent operational definitions of diseases with OWL and
      successfully classify real patient cases. Representing diagnostic criteria as
      descriptive knowledge (instead of rules in Semantic Web Rule Language or Prolog)
      allows us to take advantage of tools already available for OWL. While we focused
      on Assessment of SpondyloArthritis international Society SpA criteria, we believe
      that many of the representation issues addressed here are relevant to using OWL
      DL for operational definition of other diseases in ontology.

PMID- 22462195
TI  - [The demographic situation and    demographic policies in Hungary after World War
      II].

PMID- 22462196
TI  - ITOHealth: a multimodal middleware-oriented integrated architecture for
      discovering medical entities.
AB  - Emergency healthcare is one of the emerging application domains for information
      services, which requires highly multimodal information services. The time of
      consuming pre-hospital emergency process is critical. Therefore, the minimization
      of required time for providing primary care and consultation to patients is one
      of the crucial factors when trying to improve the healthcare delivery in
      emergency situations. In this sense, dynamic location of medical entities is a
      complex process that needs time and it can be critical when a person requires
      medical attention. This work presents a multimodal location-based system for
      locating and assigning medical entities called ITOHealth. ITOHealth provides a
      multimodal middleware-oriented integrated architecture using a service-oriented
      architecture in order to provide information of medical entities in mobile
      devices and web browsers with enriched interfaces providing multimodality
      support. ITOHealth's multimodality is based on the use of Microsoft Agent
      Characters, the integration of natural language voice to the characters, and
      multi-language and multi-characters support providing an advantage for users with
      visual impairments.

PMID- 22462197
TI  - [The medical debate about the Hungarian vampires, 1732-56].

PMID- 22462198
TI  - The Norrland crop failures of 1902 and the Swedish Americans.

PMID- 22462199
TI  - Measles virus nomenclature update: 2012.

PMID- 22462200
TI  - Global Polio Eradication Initiative: fifth meeting of the Independent Monitoring
      Board.

PMID- 22462201
TI  - Family ties that bind: Anglo-African slave traders in Africa and Florida, John
      Fraser and his descendants.

PMID- 22462202
TI  - Recommended composition of influenza virus vaccines for use in the 2012-2013
      northern hemisphere influenza season.

PMID- 22462203
TI  - Slave society in the sugar plantation zones of Saint Domingue and the Revolution
      of 1791-93.

PMID- 22462204
TI  - Antigenic and genetic characteristics of zoonotic influenza viruses and
      development of candidate vaccine viruses for pandemic preparedness.

PMID- 22462205
TI  - The upbringing and education of women as represented in novels by nineteenth
      century Polish women writers.

PMID- 22462206
TI  - [The problem of prostitution during China's early    urban modernization].

PMID- 22462207
TI  - [On the bipolar spectrum].

PMID- 22462208
TI  - [Psychopathology, therapeutic implication and differential diagnosis of bipolar
      disorders].

PMID- 22462209
TI  - [Position of the psychiatrist in diagnosis and treatment of acute psychiatric
      diseases--from the viewpoint of categories and dimensions].

PMID- 22462210
TI  - [Videoendoscopic surgery].

PMID- 22462211
TI  - [Are laparoscopic operations on stomach useful?].
AB  - The purpose of this review is to assess the position of laparoscopic gastric
      surgery. Only for perforated gastric and duodenal ulcers a prospective randomized
      study is available without revealing meaningful differences between conventional
      and laparoscopic procedure. The elective laparoscopic Selective Proximal Vagotomy
      (SPV) of stomach and duodenal ulcers was reported on some 200 patients till now.
      The perioperative risk was lower than that of the conventional method. Due to
      only short follow-up statements on the risk of ulcer recurrence and therefore
      completion of vagotomy can not be made. Because of operative technical
      difficulties some examinators have modified the Selective Proximal Vagotomy, but
      long-term results with these techniques and the conventional method do not exist.
      Till now a laparoscopic resection of the stomach was done in less than 100
      patients. At comparable risk of both methods representative conclusions could not
      be made. Similar small are the experiences with laparoscopic resection of the
      stomach or gastrectomy for gastric carcinoma. The results suppose that a
      systematic lymph node dissection of the compartment II is only restrictevly
      possible. The operative risk is nearly that of the conventional method.
      Laparoscopic staging is a favourable indication in gastric surgery with the aim
      to detect peritoneal metastases and to spare the patient an exploratory
      laparotomy. Furthermore, laparoscopy offers advantages in palliative procedures,
      without existence of extensive proof. Nowadays it is applied for extreme obesity
      and "Gastric Banding", a method with low perioperative risk. Whether the long
      term results are equivalent to those of conventional stomach bypass operations is
      not proved so far. Alltogether the advantages of laparoscopy in comparison to
      conventional gastric surgery are only obvious in a few clinical situations.
      Qualified randomized prospective studies are necessary to evaluate the new
      operation techniques.

PMID- 22462212
TI  - [Laparoscopic wedge resection of the stomach for early gastric cancer using a
      lesion-lifting-method: curative and minimally invasive treatment].
AB  - Thirty-eight patients with early gastric cancer have been successfully treated by
      laparoscopic wedge resection of the stomach in our institute since March 1992.
      Our indication of the surgery is as follows: 1) preoperatively diagnosed mucosal
      cancer, 2) < 25 mm, if the lesion is elevated type, and 3) < 15 mm and no ulcer
      scar, if the lesion is depressed type. After laparoscopic exposure of the gastric
      wall around a cancerous lesion, a sheathed needle was inserted into the stomach
      through the abdominal wall at the vicinity of the lesion under gastroscopy
      guidance. A small metal rod was introduced into the stomach near the lesion
      through the outer sheath. While the lesion was lifted up precisely with the
      support of the metal rod, wedge resection of the stomach was performed using an
      endoscopic stapler (lesion-lifting method). Perigastric lymph nodes could be also
      resected when necessary. There was no intraoperative and postoperative
      complication, and no mortality. The patients were discharged within 5 days after
      surgery uneventfully. The resected specimens were 50 to 110 mm in diameter, and
      there was a sufficient surgical margin (16 +/- 5mm). All patients have survived
      during the 2 to 60 months follow-up period. There has been one recurrence and one
      separate occurence of early gastric cancer in the series, which were curatively
      treated by gastrectomy. Advantages of the surgery are as follows: 1) it is
      minimally invasive, 2) most of the stomach is preserved, 3) a sufficient surgical
      margin can be obtained, and 4) a detailed histologic examination is feasible. If
      the indication is selected properly, this laparoscopic surgery can be a curative
      and minimally invasive treatment for early gastric cancer.

PMID- 22462213
TI  - [Laparoscopic resection of colorectal cancer].
AB  - Laparoscopic colorectal surgery is not always accepted in the surgical community.
      However, there are now sufficient data available to recommend laparoscopic
      techniques in colorectal surgery. The morbidity following laparoscopic surgery is
      not higher than after conventional surgery, it may even be lower. Postoperative
      mortality appears to be similar. The conversion rate depends on the learning
      curve and indications to perform laparoscopic surgery and may even be 35%. After
      laparoscopic surgery, there is better lung function, less pain, shorter period of
      ileus and less immunosuppression. The major disadvantages are longer operative
      time and higher costs. Long-term results are not available yet. But it seems that
      the recurrence rate is not higher. The incidence and pathogenesis of trocar site
      metastases are unknown. Surgcial concepts to avoid these sequelae are not
      established. Long-term results have to be available from prospective-randomized
      trials before laparoscopic surgery can be recommended for malignancies.

PMID- 22462214
TI  - [Laparoscopic colorectal surgery in routine at a municipal hospital].
AB  - The importance of laparoscopic techniques in colorectal surgery as routine
      service in a municipal hospital is described in a prospective study. PATIENTS AND
      METHOD: From April 1993 to March 1997 359 patients were operated laparoscopically
      for colon and rectum diseases in the surgical department of the municipal
      hospital Zehlendorf Berlin, local area Behring. In the beginning we operated only
      patients with benign disorders. Since July 1995 patients with colorectal
      malignancies were resected on the basis of oncological criteria within a
      multicenter prospective trial. 149 patients (41.5%) were operated for benign
      colorectal diseases. 93 patients (25.9%) had diverticulosis, diverticulitis or
      benign tumors. 26 were resected in MIS-technique for rectum prolapse. 180
      patients presented with colorectal malignancies and were operated in 153 cases
      (42.9%) with curative intention. RESULTS: Mean operation time was between 60 and
      520 min. Learning curve reduces after 40 operations operation time significantly.
      Severe complications appeared in 4.5% of all cases.

PMID- 22462215
TI  - [Influence of laparoscopic or conventional colorectal resection on postoperative
      quality of life].
AB  - In a prospective randomised study the influence of the operative technique on
      postoperative quality of life was evaluated in 60 patients undergoing
      laparoscopic (n = 30) or conventional (n = 30) resection of colorectal tumors.
      Quality of life was assessed using the European Organisation for Research and
      Treatment of Cancer Quality of Life Core 30 Questionnaire (EORTC-QLQ-C30) before
      surgery as well as 1 week, 4 weeks and 3 months after surgery. Age, sex,
      sociological parameters, tumor characteristics and type of resection were
      comparable in both groups. There were no significant differences in preoperative
      global quality of life, the functional aspects of quality of life and the
      severity of disease related symptoms. The global quality of life was
      significantly better in the laparoscopic group compared to the conventional group
      1 week and 4 weeks after surgery (p = 0.05). Physical and emotional function were
      more impaired 1 week after conventional compared to laparoscopic surgery (p <
      0.05). Pain, dyspnea and loss of appetite were more severe 1 week after
      conventional than laparoscopic surgery (each p < 0.05). There were no differences
      in quality of life in the further postoperative course. Laparoscopic resection of
      colorectal tumor is related with a better short-term quality of life than
      conventional resection, but a longer lasting effect of the laparoscopic technique
      on quality of life could not be detected with the EORTC-QLQ-C30.

PMID- 22462216
TI  - [Atypical laparoscopic liver resection].
AB  - The laparoscopic resection of small benign hepatic lesions located peripherally
      is described in three cases. The histology revealed adenomas in two patients and
      a focal nodular hyperplasia in a third patient. The area of resection measured
      between 9 and 15 cm2. Following laparoscopic endosonography with localisation of
      adjacent vascular structures to the tumor the lesion was resected by combined
      ultrasonographic dissection (endocusa) and clipligature. Bloodloss was limited to
      a maximum of 130 ml. The time of hospitalisation was 3 to 5 days.

PMID- 22462217
TI  - [Role of endoscopic adrenalectomy in adrenal gland surgery].
AB  - Endoscopic techniques are used increasingly in adrenal gland surgery. In this
      paper the indications and results of the laparoscopic and retroperitoneoscopic
      approach are compared to the results of the conventional trans- and
      extraperitoneal approach. Endoscopic adrenalectomy can be performed safely and
      with the benefits associated with minimally invasive surgery. Disadvantages of
      the laparoscopic, transperitoneal approach are the risk of an intraabdominal
      injury and the problems caused by adhesions after abdominal operations. The
      retroperitoneoscopic approach avoids these disadvantages. Anatomical orientation
      is more difficult using the retroperitoneoscopic access. In case of large tumors
      of the adrenal gland suspected for malignancy we see the indication for the
      conventional transperitoneal approach.

PMID- 22462218
TI  - [85 consecutive VATS non-rib spread simultaneously stapled lobectomies for
      malignancy].
AB  - A new technique for pulmonary lobectomy has been utilized for malignant lesions.
      Eighty-five consecutive patients with pulmonary neoplasms underwent a VATS non
      rib spread Simultaneously Stapled Lobectomy. There were 34 males and 51 females
      with 61 adeno, 21 squamous, 2 large cell and 1 carcinoid tumor who underwent 18
      left upper, 13 left lower, 20 right upper, 7 right middle and 27 right lower
      lobectomies. Forty-one mediastinoscopies were negative. Patients with positive
      mediastinoscopies were not selected for curative resection. At VATS exploration,
      10 patients had positive nodes. All resected nodes were negative in the other
      patients. Every bronchoscopy was negative. Operating times averaged 84.5 minutes.
      No patient received a transfusion. Lesions ranged from 1 cm to 8 cms with an
      average size of 3.62 cms. Post-operative length of stay averaged 3.38 days. There
      was no surgical mortality, no hemorrhage, no transfusion and no conversion to an
      open case in the entire series. No bronchial, vascular or broncho vascular
      fistula occurred. Complications were minor from which all patients recovered
      completely. Survival seems similar to patients resected by traditional open
      techniques.

PMID- 22462219
TI  - [Thoracoscopic thymectomy for treatment of myasthenia gravis].
AB  - BACKGROUND: While thymectomy has been established for most of the stages of
      myasthenia gravis (MG) the optimal surgical approach for thymectomy remains a
      matter of discussion. Complete thoracoscopic thymectomy has been developed as a
      minimally invasive technique. Clinical application of thoracoscopic thymectomy
      has been investigated. PATIENTS/METHODS: A standardized technique for
      thoracoscopic thymectomy has been developed. In the the supine position with the
      operated left side elevated at approximately 30 degrees from the horizontal 3
      trocars were placed between 3rd and 5th left intercostal spaces. Between 10/1994
      and 5/1997 16 patients (12 female, 4 male, mean age 35 +/- 12 years) were
      prospectively selected for thoracoscopic thymectomy. RESULTS: In 15 cases the
      indication was MG (Ossermann stage 1-1, stage 2a-7, stage IIb-7 patients), 3
      patients had a thymoma, in 2 of these patients both MG and thymoma were found. In
      1 case a conversion to median sternotomy was necessary for technical reasons. The
      mean operation time was 132 +/- 47 minutes. All of the histological findings of
      the thymus were benign. Preliminary results with a mean follow-up of 16.4 +/-
      10.1 months showed equal improvement rates of MG after thoracoscopic thymectomy
      as compared to conventional thymectomy. There was no perioperative mortality, and
      morbidity comprised one bleeding, one leakage of the thoracic duct and two
      pleural effusions. DISCUSSION: Complete thoracoscopic thymectomy is technically
      feasible with an acceptable learning curve. A very low postoperative morbidity
      and convincing short-term results have led to high acceptance by patients and
      neurologists. Long-term results and prospective comparison with median sternotomy
      may result in thoracoscopic thymectomy to become the operative approach of choice
      for selected cases.

PMID- 22462220
TI  - [Future of endoscopic surgery--German health law and minimal access surgery in an
      university hospital].
AB  - The future development of endoscopic surgery depends on a medical and economical
      benefit. Medical advantages are demonstrated under professional conditions of
      practice in a retrospective study: endoscopical repair of the groin (TEP n = 44)
      vs. conventional Shouldice- (n = 17) and Lichtenstein (n = 19) method,
      laparoscopical hemifundoplication (n = 7) vs. traditional Nissen-Rosetti
      procedure (n = 3) and also resection of the sigmoid (lap. n = 26) vs. open
      surgery (n = 12). The overall hospital stay is shortend dramatically (primary
      hernia of the groin 8.8 (Shouldice) and 7.4 (Lichtenstein) vs. 3.1 days (TEP);
      (hemi-) fundoplication 11.1 (open) vs. 5.0 days (lap.); resection of sigmoid 19.0
      (open) vs.17.0 days (lap.)) At the same time quality of care is held or improved.
      Comparison of real cost analysis revealed a better economical result (593-970 DM
      lower cost for TEP, 1.256 DM lower costs for lap. hemifundoplication, and 1.918
      DM in case of lap. resection of sigmoid) for minimal-access-surgery (MAS),
      although particular costs for the endoscopic surgical procedure are increasing up
      to 100%, especially at the beginning (learning curve). The German payment-system
      does not regard the special conditions of MAS. There is no case-related payment
      for MAS due to the lower overall costs. Therefore the financial result is worse
      than for conventional treatment.

PMID- 22462221
TI  - [Immunocytochemical detection of cytokeratin positive cells in human bone marrow
      of gastric and colorectal cancer patients].
AB  - We looked for disseminated tumour cells postoperatively in the bone marrow of 22
      patients with gastric cancer and of 26 patients with colorectal cancer. On an
      average the follow-up was 6.5 months in the gastric cancer group and 9 months in
      the colorectal cancer group. In 27% of the gastric cancer group and in 30% of the
      colorectal cancer group follow-up aspirates were obtained. Micrometastases were
      detected in 96% of colorectal cancer patients and in 77% of gastric cancer
      patients. Both, postoperative and follow-up aspirations showed clear differences
      in the number of ck+ cells between the iliac crest sides. The majority of cells
      formed clusters from 2 to about 200 cells. In both groups no significant
      correlation was found between the number of tumour cells detected and the
      established risk factors (stage, tumour extension, lymph node involvement,
      distant metastasis) or the disease-free survival. In the gastric cancer group
      higher numbers of ck+ cells were seen in the low tumor stages I and II, as
      compared to stage III and IV. Besides, in this group significantly more ck+ cells
      were detected in younger patients (age under 63,5) than in the older group over
      63,5 years. Colorectal cancer patients did not show this correlation. In follow
      up aspirations the number of ck+ cells of the colorectal and also the gastric
      cancer group showed a tendency of rise in relapse and of fall in disease-free
      survival. There was a tendency of higher rates of ck+ cells in the colorectal
      cancer group when compared to gastric cancer patients.

PMID- 22462222
TI  - [Severe obstipation in the mentally ill and disabled].
AB  - Severe constipation is a well recognized symptom amongst disabled or mentally ill
      patients. Characteristically, these patients live without bowel movements for
      days and present themselves with abdominal distension and fecal impaction.
      Inpatient treatment is necessary frequently. Due to intestinal obstruction,
      diagnostic approaches are often delayed because of lack of cooperation. Data of
      94 disabled patients with severe obstipation are presented. 54 patients were
      admitted to inpatient treatment of constipation or bowel obstruction, 40 were
      treated for another diagnosis but had severe constipation which required
      intervention. Ileus or conservatively untreatable constipation led to 16
      operations in 14 patients (polypectomy 2, rectopexy 1, cecostoma 5, left
      hemicolectomy 3, subtotal colectomy 5). Cecostomata are considered not to be
      effective as definite treatment whereas colonic resection resulted in daily bowel
      movements.

PMID- 22462223
TI  - [A modular retraction system (VarioLift) for laparoscopy without
      pneumoperitoneum].
AB  - Because of adverse physiological effects and technical disadvantages of the
      pneumoperitoneum, alternative methods of abdominal wall lifting have been
      explored recently. Most of these systems are complicated in their system set-up
      and handling or the intraabdominal exposure is limited. The modular retraction
      system (VarioLift, AESCULAP Tuttlingen) consists of two different components, one
      for the abdominal wall lifting, and one for internal organ compression. Via a 2
      cm mini-laparotomy two lifting parts of different size and shape are introduced
      into the abdominal cavity, assembled to each other and attached to an outside
      mechanical lifting arm which is suspended to the operating table. Using
      combinations of these parts, the system can be adjusted to different abdominal
      quadrants and the patient's individual anatomy. According to the needs of vision
      for internal organ compression a translucent plastic membrane can be placed for
      posterior organ retraction using the same access. In contrast to other systems
      the modular retraction system (VarioLift) allows an individual adjustment to the
      patient's anatomy and, if necessary, compression of internal organs. A planar
      suspension of the abdominal wall with a good lateral exposure and a dome-shaped
      suspension without tenting effects is provided. Time needed for mini-laparotomy
      and system set-up is only slightly longer than installation of a
      pneumoperitoneum.

PMID- 22462224
TI  - [Head trauma].

PMID- 22462225
TI  - [Laparoscopic surgery--pro and contra--in and out].

PMID- 22462226
TI  - [The white clot syndrome].
AB  - The white clot syndrome is a serious ideosyncratic side effect of routine
      anticoagulation with low dose heparin. Two different courses of the white clot
      syndrome are illustrated. The different ways of diagnosis and therapy as well as
      means of prophylaxis are discussed.

PMID- 22462227
TI  - [Combined radiochemotherapy of an irresectable carcinoma of the pancreas].
AB  - Local irresectable carcinoma of the pancreas was diagnosed by explorative
      laparotomy of a 62-years old patient. At this stage (T3 N1 M0), a curative
      surgical therapy was not possible. The prognosis in these cases is bad. Medium
      survival time is less than half a year. In order to improve prognosis a combined
      radiochemotherapy has been applied. The total tumor dose of 44.8 Gy was applied
      in 2 daily fractions of 1.6 Gy. On the first 3 days of radiotherapy 600 mg/m2 5
      FU and 300 mg/m2 folinic acid were given i.v.. Chemotherapy was repeated each 28
      days. After 45 months of observation and application of 20 courses chemotherapy
      no local or systemical progress can be proven in this patient. His health status
      is good. A combined radio-chemotherapy improves prognosis in locally irresectable
      carcinoma of the pancreas. In particular cases survival time is surprisingly
      long.

PMID- 22462228
TI  - Thoughts on intervention in HIV/AIDS with traditional Chinese medicine.
AB  - HIV/AIDS has become a worldwide pandemic and highly active antiretroviral therapy
      (HAART) is the only generally recognized effective therapy at present. However,
      various unresolvable problems appear with the widespread use of HAART.
      Traditional Chinese Medicine shows good efficacy for intervention in HIV/AIDS and
      could become an effective treatment option.

PMID- 22462229
TI  - Characteristics and advantages of traditional Chinese medicine in the treatment
      of acute myocardial infarction.
AB  - OBJECTIVE: To obtain epidemiological data on Traditional Chinese Medicine (TCM)
      therapeutic status of acute myocardial infarction (AMI) and to determine TCM
      characteristics and advantages to improve the level of TCM prevention and
      treatment of AMI. METHODS: Clinical epidemiology methods were used to register
      and survey the TCM therapeutic status of hospitalized AMI patients. In 2001, the
      Chinese Association of Integrative Medicine surveyed the therapeutic status of
      3308 AMI patients hospitalized in 30 hospitals in Beijing and Shanghai from 2000
      2001. The Beijing Collaborative Study Group on Therapeutic Status of Acute
      Myocardial Infarction (the Study Group) then conducted a 10-year-long register
      survey on hospitalized AMI patients in Third-grade A-Level TCM hospitals in
      Beijing. After 2002, the Study Group further surveyed the treatment conditions of
      AMI-hospitalized patients in 10 Second-grade A-Level TCM hospitals. The
      therapeutic status in 8 Third-grade A-Level Western medicine hospitals was
      surveyed in 2001 and 2005 as a control. In 2008, in cooperation with the China
      Association of Chinese Medicine, the Study Group further performed a survey at 26
      Third-grade A-Level TCM hospitals nation-wide. Approximately 5000 cases were
      investigated to obtain authoritative data on the therapeutic status of AMI
      patients in TCM hospitals in China. RESULTS: We found that Chinese herbal
      intravenous preparations may be beneficial in reducing the mortality of AMI.
      Major complications of AMI, such as heart failure and arrhythmia, were
      significantly less during the 10-year survey period. The mortality of
      hospitalized AMI patients showed a decline. TCM treatment was helpful for AMI
      patients in improving their quality of life. Ten-year dynamic monitoring showed
      that the ability to perform reperfusion and to use drugs appropriately, as well
      as an effort to carry out the Clinical Guidelines has made great progress in TCM
      hospitals. However, TCM hospitals still have some problems in treating AMI,
      including a lack of standardized TCM syndrome diagnosis, the need for syndrome
      differentiation and treatment standardization, and clinical skills in reperfusion
      and standardized drug treatment still need to be further improved. Compared with
      AMI patients in Western medicine hospitals during the same period, those in TCM
      hospitals had the following characteristics: they were admitted to hospital
      later; they were older when they had a heart attack; there were more females,
      they had more problems in their medical history, and they had more concomitant
      illnesses and complications. Therefore, the demographic baseline data were
      significantly different between AMI patients in TCM hospitals and those in
      Western medicine hospitals. This indicated that patients in TCM hospitals were
      more critical than those in Western medicine hospitals. CONCLUSIONS: TCM has
      special advantages in treating AMI. TCM hospitals are making continuous progress
      in standardized treatment of AMI, but further improvement is still required. AMI
      patients in TCM hospitals have some special characteristics, and their condition
      may be more critical. Further clinical research on TCM treatment of AMI is
      required.

PMID- 22462230
TI  - Logistic regression analysis of syndrome essential factors in patients with
      unstable angina pectoris.
AB  - OBJECTIVE: To explore the correlation between common syndrome essential factors
      and the symptoms and signs of unstable angina (UA). METHODS: Eight hundred and
      fifteen patients with UA confirmed by coronary angiography were identified from
      several centers. Common syndrome essential factors were selected on the basis of
      expert experience. The correlations between common syndrome essential factors and
      symptoms and signs of UA were analyzed using binary logistic regression analysis.
      RESULTS: The common syndrome essential factors in unstable angina were blood
      stasis, qi stagnation, phlegm turbidity, heat stagnancy, qi deficiency, yin
      deficiency, and yang deficiency. Symptoms such as chest pain, hypochondriac
      distention, ecchymosis, dark orbits, dark and purplish tongue, and tongue with
      ecchymosis and petechiae were significant diagnostic features of "blood stasis".
      Aversion to cold and cool limbs, weakness in the waist and knees, and clear
      abundant urine were significant diagnostic features of"yang deficiency". These
      results were in accordance with the understanding of traditional clinical Chinese
      medical practice. CONCLUSION: This clinical study analyzed the correlations
      between common syndrome essential factors and the symptoms and signs of unstable
      angina. The results provide the basis for establishing diagnostic criteria for
      syndrome essential factors.

PMID- 22462231
TI  - Multi-central clinical research into treating 80 cases of chronic
      thrombocytopenia with qi-supplementing and yin-nourishing therapy and western
      medicine.
AB  - OBJECTIVE: To probe the effects of qi-supplementing and yin-nourishing therapy
      (blood-increasing decoction and blood generating powder) on chronic
      thrombocytopenia. METHODS: Two hundred patients with chronic thrombocytopenia
      were randomly divided into control (n = 100) and test groups (n = 100) with Amino
      polypeptide as a basic treatment for both. Test group patients consumed a blood
      increasing decoction and blood-generating powder for 1-3 months. Improvements in
      platelet counts and TCM syndrome were observed. RESULTS: One hundred and sixty
      four (80 in the test group and 84 in the control group) of 189 total participants
      were treated for 3 months. The total effective rate in improving TCM syndrome was
      95.00% in the test group and 79.76% in the control group (P < 0.05). There was
      significant difference (P < 0.05) in the accumulated score of TCM syndrome
      between the two groups treated at different time points. The total effective rate
      of platelet counts was 86.25% in the test group and 59.52% in the control group
      (P < 0.05). There was a significant difference in platelet counts before and
      after treatment in the two groups (P < 0.05). There was no significant
      differences in platelet count between the two groups treated for 1-2 months;
      however, a significant difference was found between the two groups after
      treatment for 3 months (P < 0.05). CONCLUSIONS: After a 3-month treatment of
      chronic thrombocytopenia patients with qi-supplementing and yin-nourishing
      therapy, TCM syndrome was improved and platelet counts increased with no obvious
      side effects, and the quality of life of the participants was enhanced with
      noticeable long-term curative effects.

PMID- 22462232
TI  - Effects of the Ganning formula on liver fibrosis in patients with chronic
      hepatitis B.
AB  - OBJECTIVE: To investigate the clinical efficacy and safety of the Ganning formula
      for the treatment of liver fibrosis in patients with chronic hepatitis B.
      METHODS: In a multicenter, randomized, controlled clinical trial, 150 patients
      with liver fibrosis secondary to hepatitis B virus (HBV) infection were randomly
      assigned in equal numbers to receive either the Ganning formula (a Chinese herbal
      decoction; active treatment group) or oral entecavir (control group) for two 3
      month courses. Patients were monitored for any treatment-induced changes in liver
      function test parameters (ALT, AST, and GGT), liver fibrosis markers (LN, HA, IV
      C, and PCIII), HBV DNA level, hepatosplenic imaging, quality of life scores, or
      psychological and social functioning scores. Patients were also observed for any
      adverse effects. RESULTS: After treatment, patients in both groups experienced
      significant improvements in liver function, HBV DNA load, hepatosplenic B-mode
      ultrasonography, quality of life, and psychological and social functioning (P <
      0.05 or P < 0.01). Patients receiving the Ganning formula achieved greater
      improvements in HA, IV-C, quality of life, and psychological and social
      functioning compared with those on entecavir (P < 0.05 or P < 0.01). There were
      no abnormal changes in blood tests, urine, feces, renal function, or
      electrocardiogram. Additionally, no adverse effects were observed in any patients
      in either group. CONCLUSIONS: The Ganning formula appears to have the potential
      to inhibit liver fibrosis and therefore improve liver function by inhibiting HBV
      replication in patients with chronic hepatitis B. Additionally, this formula is
      helpful in improving quality of life and psychological and social functioning.

PMID- 22462233
TI  - A systematic review of RCTs and quasi-RCTs on traditional Chinese patent
      medicines for treatment of chronic hepatitis B.
AB  - Traditional Chinese patent medicines (TCPMs) are widely used for treatment of
      chronic hepatitis B (CHB) in China. To estimate the overall effectiveness of
      TCPMs for CHB, we performed a systematic review of clinical reports designed as
      randomized controlled trials (RCTs). One hundred and thirty-eight available RCTs
      and quasi-RCTs on 62 TCPMs, involving 16,393 patients, were included. The
      methodological quality of these trials was generally "poor". Few trials (6.52%)
      reported the methods of randomization correctly. Another common problem was the
      lack of allocation concealment, proper blinding, and the reporting of lost cases
      and dropouts. Forty-two trials (30.43%) on 27 TCPMs reported some anti-viral
      effect of TCPMs. Others reported beneficial aspects, including improvements of
      liver function (79.71% of the studies), liver fibrosis (29.99%), and CHB symptoms
      (92.75%). Forty-one articles (29.71%) reported mild adverse events with TCPMs but
      these occurred infrequently. In summary, the outcome of the report on currently
      registered TCPMs may be biased due to poor methodology. The data from these
      trials, therefore, is too weak to use in forming a recommendation for treatment
      of CHB. Nevertheless, five drugs (Dan Shen agents, Da Huang Zhe Chong
      pill/capsule, Shuang Hu Qing Gan granule, Fu Zheng Hua Yu granule and Cao Xian Yi
      Gan capsule) appear to be more effective than the other TCPMs.

PMID- 22462234
TI  - Safety of individual medication of Ma Qian Zi (semen strychni) based upon
      assessment of therapeutic effects of Guo's therapy against moderate fluorosis of
      bone.
AB  - OBJECTIVE: To assess the safety of individual medication of Guo's Ma Qian
      Decoction on the basis of effective treatment of fluorosis of bone with Guo's
      therapy. METHODS: One hundred and fourteen cases of moderate fluorosis of bone
      were randomly divided into a treatment group (n = 60) and a control group (n =
      54) between December 2007 and August 2009 by using the block randomized method
      and a central random system. At the same time of basic treatment, the patients in
      the treatment group were orally administrated with Guo's Ma Qian Decoction. The
      initial dose of Ma Qian Zi (Semen Strychni) was 0.4 g and increased by 0.05 g
      every two days, with the doses of other drugs unchanged, until the patient had
      "nux vomica response". For the patients with no "nux vomica response", the dosage
      was continued to increase and the maximum dosage was not more than 1.2 g/day. The
      control group was treated with decoction placebo. The changes of strychnine and
      brucine contents before and after processing and after decoction of Ma Qian Zi
      (Semen Strychni) were determined with reversed-phase high-performance liquid
      chromatography, which were controlled within ranges stipulated in the
      Pharmacopeia; Adverse events were analyzed; Blood strychnine and brucine contents
      in 10 cases who had taken the drugs were determined. RESULTS: 1) Strychnine
      (2.125%) and brucine (1.425%) contents before processing of Ma Qian Zi and 1.88%
      and 1.31% after processing all conformed with the standards of strychnine (1.2
      2.2%) and brucine (no less than 0.8%) stipulated in the Pharmacopeia. When the
      maximum dosage of Ma Qian Zi was 1.2 g/day, strychnine in the decoction was 11.17
      mg and brucine was 7.44 mg, which all conformed with the maximum limited amount
      (strychnine 13.32 and brucine no less than 4.8 mg) stipulated in the
      Pharmacopeia. 2) Eight cases had "nux vomica response" in the treatment group and
      one case in the control group, with a significant difference between the two
      groups (P < 0.05). 3) Altogether 18 cases had adverse events, with an incidence
      rate of 15.38% (8 cases) in the treatment group and 18.52% (10 cases) in the
      control group, with no difference between the two groups (P > 0.05); Among them,
      10 cases (8.77%) with the adverse event were not related with therapeutic drugs,
      with an incidence rate of 6.67% (4 cases) in the treatment and 11.11% (6 cases)
      in the control group, with no significant difference between the two groups (P >
      0.05). Seven cases had suspicious relative adverse events, the risk in the
      treatment group was 0.658 times of the control group, with no significant
      difference (P > 0.05), and one case had the toxic reaction of nux-vomica seed. 4)
      Strychnine and brucine were unable to be detected in the blood in all points of
      time in the 10 cases who had taken the drugs, indicating that plasma strychnine
      and brucine contents were lower than the minimum detectable amount (10 ng), and
      accumulation of strychnine and brucine were not found in blood of the patient
      during and after administration for 8 weeks. CONCLUSION: The individual
      medication of Ma Qian Zi (Semen Strychni) in the Guo's therapy has a better
      safety.

PMID- 22462235
TI  - A study of the law of herbal administration in treating lung-distension by TCM
      physicians through history using cluster analysis.
AB  - OBJECTIVE: To review the herbal drugs used most often for treating lung
      distension by determining those used by physicians throughout history; to study
      their property, taste, and channel tropism; and to explore their compatibility.
      METHODS: Historical prescriptions for treating lung-distension were collected and
      sorted. Property, taste and channel tropism were determined, and the law of
      herbal administration was determined by cluster analysis. RESULTS: One hundred
      and ninety five prescriptions were found, involving 166 herbal drugs, with a
      total appearance frequency of 1296 drugs. The herbs involved 8 properties (total
      appearance frequency, 1296), 7 forms of taste (total appearance frequency, 1991)
      and involved all 12 regular channels (total appearance frequency, 3382). Sixteen
      herbal drugs were used most often and formed 4 cluster prescriptions: C1: Xing
      Ren (Semen Armeniacae Amarum), Gan Cao (Radix Glycyrrhizae), and Ban Xia (Rhizoma
      Pinelliae); C2: Gui Zhi (Ramulus Cinnamomi), Wu Wei Zi (Fructus Schisandrae), and
      Sheng Jiang (Rhizoma Zingiberis Recens); C3: Da Zao (Fructus Jujubae), Ma Huang
      (Herba Ephedrae), and Shi Gao (Gypsum Fibrosum); and C4: Chen Pi (Pericarpium
      Citri Reticulatae), Jie Geng (Radix Platycodi), Fu Ling (Poria), Sang Bai Pi
      (Cortex Mori), Xi Xin (Herba Asari), Gan Jiang (Rhizoma Zingiberis), and Bai Shao
      (Radix Paeoniae Alba). CONCLUSION: In treating lung-distension, phlegm retention
      has been traditionally considered the underlying pathology, emphasizing
      regulation of the lung and spleen as key and stressing patient nourishment and
      mental improvement. Prescriptions for lung-distension should be made with
      reference to the property, taste, channel tropism, and effectiveness of the
      chosen herbal drugs.

PMID- 22462236
TI  - Acupuncture in preterm babies during minor painful procedures.
AB  - OBJECTIVE: To evaluate analgesic effects of acupuncture in preterm neonates
      during minor painful procedures. METHODS: Ten preterm neonates requiring heel
      prick for blood gas analysis were enrolled in the study, which had a crossover
      design. Oxygen saturation, systolic and diastolic blood pressure, respiratory
      rate, heart rate, and crying duration were recorded before and after heel prick.
      Babies were given expressed breast milk before each procedure. Patients were
      randomly assigned to receive acupuncture or not, and the groups were crossed over
      on the following day, so that patients who had received acupuncture received only
      breast milk, and the previous breast milk only group received both acupuncture
      and breast milk. The neonatal infant pain scale (NIPS) was used for pain
      evaluation. RESULTS: Crying duration and NIPS pain scores during heel prick were
      lower in the neonates who had received acupuncture. CONCLUSION: Acupuncture is an
      effective method for the treatment of pain in neonates.

PMID- 22462237
TI  - Observations on curative effect of high-frequency electric sparkle and point
      injection therapy on knee osteoarthritis.
AB  - OBJECTIVE: To observe the curative effect of high-frequency electric sparkle and
      point-injection therapy (HESPT) on knee osteoarthritis (KOA). METHODS: Two
      hundred and five patients were randomly divided into a warming needle moxibustion
      group (68 cases), a HESPT group (68 cases) and a point-injection group (69
      cases). In the warming needle moxibustion group, the main points of Xuehai (SP
      10), Neixiyan (EX-LE4), Waixiyan (EX-LE), Dubi (ST 35), Zusanli (ST 36) and
      Yanglingquan (GB 34), and the adjunct points of Yinlingquan (SP 9) and Sanyinjiao
      (SP 6), on the affected side, were chosen for stimulation. In the HESPT group,
      tenderness points, the main points of Liangqiu (ST 34), Xuehai (SP 10), Neixiyan
      (EX-LE4), Waixiyan (EX-LE5) and Zusanli (ST 36), and the adjunct points of
      Yinlingquan (SP 9), Weizhong (BL 40) and Chengshan (BL 57), were chosen. After
      proper manipulation, Corydalis decumbens Pers. liquid was injected into the
      points and a high-frequency electric sparkle was applied to stimulate the needles
      for 30 seconds. In the point-injection group, point injection was performed with
      the same method, but the patients did not receive electric stimulation. The
      Western Ontario and McMaster University Osteoarthritis Index (WOMAC), the Lysholm
      Knee Score Scale (LKSS) and the ROM (Range of Motion) scale were used to evaluate
      the severity of KOA and the function of knee joints before treatment and 4 weeks
      after treatment. Finally, the Nimodipine method was used to assess the total
      curative effect. RESULTS: After HESPT treatment, the scores for pain, morning
      stiffness and swelling were significantly lower (P < 0.01) and LKSS index and ROM
      were much higher (P < 0.01 and P < 0.05 respectively) compared to the two other
      groups. The obviously effective rate and total effective rate were also
      significantly higher in the HESPT group than in the two other groups (P < 0.01 or
      P < 0.05). CONCLUSION: HESPT can improve joint function in KOA patients, and the
      curative effect is better than for warming needle moxibustion or point-injection
      only.

PMID- 22462238
TI  - Effects of different scraping techniques on body surface blood perfusion volume
      and local skin temperature of healthy subjects.
AB  - OBJECTIVE: To study the mechanism and effects of different scraping techniques on
      body surface blood perfusion volume and local skin temperature of healthy
      subjects and to provide a baseline for microcirculation and energy metabolism for
      the evaluation of the therapeutic effects of scraping. METHODS: Changes of the
      local blood perfusion volume and skin temperature of healthy subjects before and
      after applying different scraping techniques were observed with a laser Doppler
      imager combined with an infrared thermographic device and the resulting data was
      analyzed with imaging and processing software for statistical analysis. RESULTS:
      Local blood perfusion volume and skin temperature all increased after both
      reinforcing and reducing scraping techniques. The value of blood flow 60 and 90
      min after the reducing technique was significantly higher than that after the
      reinforcing technique (P < 0.01), while the skin temperature increased after both
      techniques but was not significantly different between the two (P > 0.05).
      CONCLUSION: Scraping can significantly improve the local blood perfusion volume,
      increase skin temperature and promote local blood circulation and metabolism of
      tissues.

PMID- 22462239
TI  - Astragaloside IV regulates expression of ATP-sensitive potassium channel subunits
      after ischemia-reperfusion in rat ventricular cardiomyocytes.
AB  - OBJECTIVE: Astragaloside IV (AsIV) is the major effective component extracted
      from the Chinese herb Astragalus membranaceus, which has been widely used to
      treat cardiovascular disease. Recent studies have shown that AsIV can potentially
      protect the heart from myocardial ischemic injury, but the mechanisms of action
      are unknown. ATP-sensitive potassium (KATP) channels are activated during
      ischemia and exert a compensatory protective effect on cardiomyocytes. We
      therefore examined the effects of AsIV on KATP channel currents and channel
      expression in isolated rat ventricular cardiomyocytes after ischemia-reperfusion
      injury. METHODS: Forty Wistar rats were divided into five groups: control group,
      ischemia-reperfusion (IP) group, IP + glibenclamide group, IP + pinacidil group
      and IP + AsIV group. The ischemia-reperfusion injury model was established in
      enzymatically isolated ventricular cardiomyocytes by perfusion with calcium-free
      Tyrode solution for 10 min, arrest for 30 min, and reperfusion for 45 min. The
      different drugs were applied for 10-15 min, and the KATP channel current
      (I(KATP)) was recorded with voltage-clamp mode by whole-cell patch-clamp
      technique. Protein and mRNA expression of the KATP channel subunits Kir6.1,
      Kir6.2, SUR2A and SUR2B was quantified using western blotting and real-time PCR.
      RESULTS: The KATP current in IP group was significantly greater than that in
      control group (211.45 +/- 33.67 vs 83.51 +/- 23.67 pA; P < 0.01). Glibenclamide
      (10 micromol/L) blocked KATP currents, whereas both AsIV (1 mg/L) and the known
      channel opener pinacidil (50 micromol/L) significantly increased I(KATP) (P <
      0.05). Consistent with this, AsIV significantly up-regulated protein and mRNA
      expression of Kir6.1, Kir6.2, SUR2A, SUR2B (P < 0.01 vs IP group). CONCLUSION:
      The protective effects of AsIV in ischemia-reperfusion injury may be related to
      the up-regulation of several KATP channel subunits and facilitation of KATP
      currents.

PMID- 22462240
TI  - Dangfei liganning capsules attenuate the susceptibility of rat nonalcoholic fatty
      liver to carbon tetrachloride toxicity.
AB  - OBJECTIVE: To test whether nonalcoholic hepatic steatosis sensitizes carbon
      tetrachloride (CCl4)-induced liver injury, and to assess the therapeutic effect
      of Chinese medicine extracts of Dangfei Liganning capsules and their potential
      underlying mechanisms. METHODS: Male Wistar rats were fed a high-fat diet to
      induce nonalcoholic fatty liver disease (NAFLD) or a normal diet (N). Eight weeks
      later, a nonlethal dose of CCl4 was applied intraperitoneally. From the start, HF
      CCl4 rats were administered daily Dangyao extracts (D), Dangfei Liganning
      capsules (DF), or Diammonium Glycyrrhizinate (G) intragastrically. Rats were
      sacrificed 48 h after CCl4 administration. In addition to serum biochemistry,
      liver histopathology was observed using hematoxylin-eosin (HE) and oil red O
      staining, and hepatic levels of triglyceride (TG), malondialdehyde (MDA),
      glutathione (GSH), superoxide dismutase (SOD), caspase-3 activation and
      cytochrome P450 (CYP2E1) expression were assessed. RESULTS: There was almost no
      response to the nonlethal dose of CCl4 in the N control group. However, the HF
      group demonstrated massive steatosis, and elevated levels of serum ALT and AST,
      liver MDA, CYP2E1, and caspase-3 activation, whereas the levels of GSH and SOD
      were significantly decreased. All indexes assessed were dramatically worse in the
      HF-CCl4 group compared to the HF group, in addition to the more severe steatosis,
      hepatocyte ballooning, and inflammatory infiltration apparent in the
      centrilobular area. The medicines we tested affected the pathological changes in
      HF-CCl4 rats to differing degrees: DF and G led to improvements in all of the
      above examined indexes, including an obvious improvement in histopathology, and
      DF improved serum ALT and MDA levels more markedly than G, whereas D extracts
      produced only mild liver injury attenuation. CONCLUSION: Liver with NAFLD is more
      sensitive to hepatotoxicity; furthermore, the disrupted balance of oxidative
      stress and anti-oxidant defense contributes to the underlying mechanisms. Dangfei
      Liganning capsules potentially decrease this toxic susceptibility and alleviate
      liver injury in non-alcoholic fatty liver.

PMID- 22462241
TI  - Preventive administration of juanbi capsules for knee osteoarthritis: effects on
      serum MMP-2 and MMP-9 levels and cartilage repair.
AB  - OBJECTIVE: To explore the mechanism of action of Juanbi Capsules, a Chinese
      medicine for invigorating the kidney and replenishing qi, in preventing
      osteoarthritis of the knee in rabbits. METHODS: Seventy-two 4-month-old, Japanese
      long-eared white rabbits were randomly divided into 6 groups: control (group A),
      model (group B), Chinese drug; high-dose (group C), Chinese drug; mid-dose (group
      D), Chinese drug; low-dose (group E), and drug control (group F). With the
      exception of the rabbits in group A, each rabbit was subjected to plaster cast
      fixation for 6 weeks to induce osteoarthritis. In addition, rabbits were
      administrated with an intragastric injection of the Chinese drug (groups C, D and
      E) or an aminoglucose hydrochloride capsule (group F) for 4 weeks. Blood was
      drawn from the central ear artery for serum MMP-2 and MMP-9 concentrations, and
      the knee joint cartilage was harvested for gross observation and light
      microscopy. RESULTS: There were significant differences in serum MMP-2 and MMP-9
      concentrations between group B and groups C, D and E (P < 0.05), with no
      significant differences between groups D and F. Histological results showed
      various changes in tissue staining with treatment, with osteophyte and bone cyst
      formation, and superficial erosion in the articular surface of the cartilage; in
      some cases, the defect reached the mid-layer of the cartilage, and these changes
      were lower than those in the model group. CONCLUSION: Juanbi Capsules assist in
      preventing osteoarthritis in the rabbit, possibly by decreasing serum MMP-2 and
      MMP-9 levels.

PMID- 22462242
TI  - Gualou xiebai banxia decoction inhibits NF-kappa B-dependent inflammation in
      myocardial ischemia-reperfusion injury in rats.
AB  - OBJECTIVE: To evaluate the myocardial protective effect of Gualou Xiebai Banxia
      decoction GXBD) and explore the mechanisms of inhibition of NF-kappa B activation
      and blockade of inflammatory responses induced by ischemia-reperfusion in rats.
      METHODS: Twenty-four Sprague Dawley (SD) rats were randomly divided into three
      groups. Rats in the treatment group received GXBD (13 g crude drug/kg) for three
      weeks, while rats in the model control and normal control groups received equal
      volumes of distilled water. On the 22nd day, rats in the ischemia-reperfusion
      (I/R) control and GXBD-treated groups underwent 30 min occlusion of the left
      anterior descending (LAD) coronary artery, followed by 120 min reperfusion.
      Electrocardiogram was recorded, and the activities of cardiac enzymes, cytokines,
      and NF-kappaB were assessed after I/R. RESULTS: Compared with the I/R control
      group, GXBD treatment restored the activity of the specific myocardial-injury
      marker creatine kinase (CK) and lactate dehydrogenase (LDH), and inhibited the
      inflammatory response involving the nuclear factor-kappaB (NF-KB) pathway,
      including down-regulation of interleukin (IL)-1beta and IL-6, and up-regulation
      of IL-10 gene expression. CONCLUSION: GXBD strongly reduced myocardial impairment
      in our I/R model, including inhibition of NF-kappaB activation and inflammatory
      cytokine responses.

PMID- 22462243
TI  - Effects of shenlian extracts on atherosclerosis by inhibition of the inflammatory
      response.
AB  - OBJECTIVE: Inflammation plays a critical role in atherosclerosis, and this
      inflammatory reaction is being intensively studied. Shenlian Extracts, an active
      ingredient of Chinese medicinal herbs, is believed to have multiple therapeutic
      and preventive effects against human vascular diseases, including
      atherosclerosis. Our work investigated whether Shenlian Extracts serves as an
      anti-inflammatory agent during atherogenesis. METHODS: We established a model of
      atherosclerosis in rabbits using balloon angioplasty and a high cholesterol diet.
      The effects of Shenlian Extracts on vessel structure and inflammation were
      assessed by hematoxylin-eosin staining of the femoral artery, measurement of
      inflammation-related factors in serum or vascular tissue, and radioimmunoassay.
      Enzyme linked immunosorbent assays (ELISA), flow cytometry and western blots were
      also performed. RESULTS: We show that oral pre-treatment with Shenlian Extracts
      suppressed the pathological changes associated with atherosclerosis and that
      graded doses of Shenlian Extracts reduced total serum levels of cholesterol (90,
      180 and 360 mg/kg), triglyceride (180 and 360 mg/kg), and LDL-c (90, 180 mg/kg).
      Various doses of Shenlian Extracts reduced serum content of TNF-alpha (180 and
      360 mg/kg), CRP (90, 180 and 360 mg/kg) and IL-8 (360 mg/kg) (P < 0.05), but led
      to no significant changes in IL-1beta levels. Treatment with Shenlian Extracts
      also significantly reduced VCAM-1 levels (90 and 360 mg/kg) and IGF-1 levels (90
      and 180 mg/kg) in vascular tissue but had no significant effect on ICAM-1 and MCP
      1 levels. Finally, Shenlian Extracts significantly reduced the abnormal
      expression of CD18 in monocytes in a dose-dependent manner. CONCLUSION: These
      results suggest that Shenlian Extracts may play a direct role in preventing and
      treating atherogenesis by inhibiting the inflammatory reaction, providing
      insights into the possible mechanism underlying the anti-atherosclerotic actions
      of Shenlian Extracts.

PMID- 22462244
TI  - Effects of electroacupuncture on hippocampal and cortical apoptosis in a mouse
      model of cerebral ischemia-reperfusion injury.
AB  - OBJECTIVE: To observe the effects of electroacupuncture on hippocampal and
      cortical apoptosis in a mouse model of cerebral ischemia-reperfusion injury.
      METHODS: Mouse models established by repeated cerebral ischemia-reperfusion,
      followed by electroacupuncture at Shenshu, Geshu, and Baihui points. The control
      group mice were intragastrically administered Hydergine. On day 1 and 7 post
      treatment, hippocampal and cortical apoptosis was detected by terminal
      deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL), and
      apoptosis images in the hippocampal CA1 zone and cortical area were analyzed.
      RESULTS: In the model group, apoptotic cells were detected one day after
      treatment and some cellular fibers were disarrayed. By day 7 post-treatment,
      there was an increase in the number of apoptotic cells in the hippocampal CA1
      region. In addition, there were apoptotic cells in the cortical area, the
      cortical layers were thinner with localized neuronal loss and sieve-like
      lymphocyte infiltration, as well as glial cell proliferation and visible infarct
      lesions. However, in the Hydergine and electroacupuncture groups, there was a
      small number of apoptotic cells. At 7 days post-treatment in the model group,
      field number, numerical density on area, and surface density were increased.
      However, in the Hydergine and electroacupuncture groups these parameters were
      decreased (P < 0.01), with a significant difference between the two treatment
      groups (P < 0.01). CONCLUSION: Electroacupuncture treatment inhibited apoptosis
      and provided neuroprotection.

PMID- 22462245
TI  - Distribution and permeability of capillaries at the skin of the conception vessel
      and the governor vessel in healthy rabbits.
AB  - OBJECTIVE: To investigate the distribution and permeability of blood vessels on
      the Conception Vessel and the Governor Vessel in the physiological state.
      METHODS: Evans blue (EB) solution was injected into the marginal ear vein of
      healthy rabbits. Three hours after injection, the rabbits were sacrificed and the
      skin on the Conception Vessel and the Governor Vessel and the corresponding
      bilateral non-channels was collected. EB was extracted with 7:3 acetone:
      physiological saline, and the absorbance of EB at each skin tissue was measured
      with a spectrophotometer. RESULTS: The A value of EB absorbance at the Conception
      Vessel on the abdominal skin was lower than that of the corresponding bilateral
      non-channels with a statistically significant difference (P< 0.01). The A value
      of EB absorbance at the Governor Vessel on the back was higher than that of the
      corresponding bilateral non-channels (P < 0.05). There was no statistical
      difference in the A value of EB absorbance between the bilateral non-channels of
      the abdomen and the back (P > 0.05). CONCLUSION: There were differences in
      capillary distribution and permeability between the Conception Vessel, the
      Governor Vessel and the corresponding bilateral non-meridians.

PMID- 22462246
TI  - Effects of electroacupuncture at different points on colorectal distention
      induced changes in blood pressure, electrogastrogram, gastric tension and gastric
      blood flow.
AB  - OBJECTIVE: To investigate the specificity of the effects of electroacupuncture
      (EA) at different acupoints on gastric functional activity and gastric blood flow
      after colorectal distension (CRD) in the rat. METHODS: Fifty Wistar rats were
      randomly divided into 5 groups: a control group, a Zusanli group, a non-point
      group, a Taichong group and a Neiguan group. Rats were anesthetized after 18 h of
      fasting, and a rat model of nociceptive blood pressure elevation and abnormal
      electrogastrogram (EGG) and gastric tension (GT) was prepared by gasbag-induced
      CRD. EA was given bilaterally, and its effects on gastric blood flow (GBF) of the
      arcus vasculosi of the greater omentum, blood pressure, EGG fast wave properties,
      and gastric smooth muscle tension (GT) were quantified. RESULTS: CRD induced an
      increase in blood pressure that was significantly inhibited by EA at all points
      (all P < 0.05), and the inhibitory effects were greater in the Zusanli and
      Neiguan groups compared to the non-point group (both P < 0.05). CRD also caused
      reductions in GT and GBF, and in the amplitude, frequency and duration of EGG
      waves (all P < 0.05). These effects were also reversed by EA. The effects of EA
      on EGG wave amplitude, GT, and GBF were superior in the Zusanli group compared to
      the Taichong group, Neiguan group, and the non-point group. CONCLUSION: EA
      significantly counteracted CRD-induced changes in blood pressure, GBF, EGG, and
      GT. The effects of stimulation at Zusanli (ST 36) were significantly greater
      compared to other points, indicating relative specificity of this acupoint.

PMID- 22462247
TI  - Kazakh therapy on differential protein expression of Achilles tendon healing in a
      7-day postoperative rabbit model.
AB  - OBJECTIVE: To compare the effect of cast immobilization with that of early Kiymil
      arkili emdew (Kazakh exercise therapy) on the post-operative healing of Achilles
      tendon rupture in rabbits, and to observe the influence of early Kiymil arkili
      emdew on the differentially expressed proteins in the healing tendon. METHODS:
      Forty-five New Zealand white rabbits were randomly divided into three groups (Arm
      A: control group; Arm B: postoperative immobilization group; and Arm C:
      postoperative early Kiymil arkili emdew group). After tenotomy, the rabbits of
      the two experimental groups received microsurgery to repair the ruptured tendons,
      and then received either cast immobilization or early Kiymil arkili emdew
      treatment. Achilles tendon tissue samples were collected 7 days after the
      surgery, and two-dimensional gel electrophoresis and MALDI-TOF-MS technique were
      used to analyze differentially expressed proteins in the tendon tissue of the
      three Arms. RESULTS: A total of 462.67 +/- 11.59, 532.33 +/- 27.79, and 515.33 +/
      6.56 protein spots were detected by the two-dimensional polyacrylamide gels in
      the Achilles tendon samples of the rabbits in Arms A, B, and C, respectively.
      Nineteen differentially expressed protein spots were randomly selected from Arm
      C. Among them, 7 were unique, and 15 had five times higher abundance than those
      in Arm B. These included annexin A2, gelsolin isoforms and alpha-1 Type III
      collagen. It was confirmed by western blot that gelsolin isoform b, annexin A2,
      etc. had specific and incremental expression in Arm C. CONCLUSIONS: The self
      protective instincts of humans were overlooked in the classical postoperative
      treatment for Achilles tendon rupture with cast immobilization. Kiymil arkili
      emdew induced the specific and incremental expression of proteins in the repaired
      Achilles tendon in the early healing stage in a rabbit model, compared with those
      treated with postoperative cast immobilization. These differentially expressed
      proteins may contribute to the healing of the Achilles tendon via a
      mechanobiological mechanism caused by the application of Kiymil arkili emdew.

PMID- 22462248
TI  - Assessing the quality of the first batch of evidence-based clinical practice
      guidelines in traditional Chinese medicine.
AB  - OBJECTIVE: To assess the quality of the first batch of Chinese evidence-based
      clinical practice guidelines (CPGs) in Traditional Chinese Medicine (TCM) using
      the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument.
      METHODS: Evidence-based CPGs in TCM supported by the World Health Organization
      Western Pacific Regional Office (WHO/WPRO) and whose development was organized by
      the China Academy of Chinese Medical Sciences were identified and manually
      retrieved. CPGs were assessed using the AGREE instrument, and the data in each
      CPG were analyzed in terms of the six domains in the AGREE instrument: scope and
      purpose, stakeholder involvement, rigor of development, clarity and presentation,
      applicability, and editorial independence. RESULTS: Twenty-eight CPGs were
      identified, of which 26 were included in the study. The AGREE instrument rated
      the 26 CPGs in terms of the six domains. The assessment results showed the
      following average scores: for editorial independence, 84.16%; for rigor of
      development, 80.95%; for scope and purpose, 79.96%; for clarity and presentation,
      70.88%; for stakeholder involvement, 61.28%; for applicability, the average score
      was only 27.09%. In summary, nine CPGs were rated as "strongly recommended", six
      as "recommended with provision or alternation", and 11 as "unsure". CONCLUSION:
      Most of the first batch of Chinese evidence-based CPGs in TCM had significant
      shortcomings in applicability. It is suggested that special attention be paid to
      enhancing the quality of applicability when developing evidence-based CPGs in
      TCM.

PMID- 22462249
TI  - Exploration of the relationship between geographical environment and human
      diseases in ancient China.
AB  - The Yellow Emperor's Classic of Internal Medicine, created in the Warring States
      period (475 to 221 BC) described a phenomenon whereby the eastern, western,
      northern, southern, and central regions were liable to different diseases. It
      brought forward the principle of treatment in accordance with local conditions.
      Lv's Spring and Autumn Annals, Huai Nan Tzu (Huainanzi), and the Regiment of
      Health (Yangshenglun) in the Qin, Han, Wei, Jin, and Southern and Northern
      Dynasties all describe regional diseases such as goiter (endemic goiter) and
      yellowish teeth (dental fluorosis) as being caused by geologic and climatic
      factors. Zhang (miasma), first mentioned in the Han Dynasty, was considered
      related to the summer heat and dampness particular to the geographical
      environment of the south. Zhang was further associated with malaria in the Jin
      Dynasty. General Treatise on the Etiology and Symptomology of Diseases
      (Zhubingyuanhou Lun), in the Sui Dynasty, held that as a type of poisonous gas,
      Zhang was the predisposing cause of malaria, seasonal disease, and barbiers,
      among other conditions. General Guide (Zhinan Zonglun), in the Southern Song
      Dynasty, regarded Zhang malaria as a separate disease. Healthy Prescription in
      the Southern Wuling District (Lingnan Weisheng Fang), in the late Song and early
      Yuan Dynasties, explicitly put forward the concepts of cold Zhang, hot Zhang, and
      lockjaw Zhang. Guidelines for Treatment of Zhang Malaria (Zhangnue Zhinan), in
      the Ming Dynasty, maintained that cold Zhang was equivalent to malaria, while hot
      Zhang and lockjaw Zhang were equivalent to cold damage, the latter of which can
      be treated by prescriptions for cold damage. Records on Zhang gas and Zhang
      disease decreased during the Ming and Qing Dynasties.

PMID- 22462250
TI  - New rounds for med students. Revised admissions test, changing focus for
      essential skills will bring a fresh look to the next generation of physicians.
AB  - Reforms of the medical education system aim to strengthen the skills of the next
      generation of doctors and train them to provide effective patient care while
      working well with other caregivers. The restructuring of residency program
      accreditation removes small details "that some might say micromanage a program"
      while maintaining core education elements, says Dr. Thomas Nasca, left, of the
      Accreditation Council for Graduate Medical Education.

PMID- 22462251
TI  - Ratcheting up compliance. Stage 2 regs focus on electronic exchange of info.

PMID- 22462252
TI  - Medicaid suits can continue ... but court ruling doesn't address essential
      factor.

PMID- 22462253
TI  - Targeting drug shortages. Feds move to ease supplies while prosecuting resellers.

PMID- 22462254
TI  - ICD-10, stage 2 regs reign. Hot topics are showstoppers at Vegas gathering.

PMID- 22462255
TI  - Politics vs. medicine. Debate over prenatal testing shouldn't gloss over the
      science.

PMID- 22462256
TI  - Navigating tax-exempt issues. Experts offer strategies for coping with new
      benefit-reporting requirements.

PMID- 22462258
TI  - Eastern perspectives. China works on its version of reform; more Asian hospitals
      seek accreditation.

PMID- 22462257
TI  - Disparity clarity. Experts see risk of payment reforms exacerbating problems for
      patients seeking care at underperforming hospitals.

PMID- 22462259
TI  - Are we in denial?

PMID- 22462260
TI  - Malpractice rates plateauing. The only thing to fear may be fear itself.

PMID- 22462261
TI  - Malpractice policies: 5 ways a broker or agent can help. A professional who
      understands the market could be well-suited to finding a policy that meets your
      needs.

PMID- 22462262
TI  - End-of-life decision-making. As a physician, it is your duty to discuss the
      wishes of your patients sooner rather than later.

PMID- 22462263
TI  - Rev up your EHR: how to optimize performance. Learn ways to increase revenue,
      improve practice efficiency and quality.

PMID- 22462264
TI  - App-solutely fabulous. Hundreds of new apps for iPAD and tablets make mHealth a
      reality and a lifestyle choice.

PMID- 22462265
TI  - The perils of vicarious liability. Why you may be responsible for the
      professional actions of the physician with whom you share space.

PMID- 22462266
TI  - Potential problems exist in the Medicare enrollment process.

PMID- 22462267
TI  - Annual Medicare payment battle. Physicians are once again staring down into the
      abyss.

PMID- 22462268
TI  - [Important symbol put requirements].

PMID- 22462269
TI  - [The Neurosedyn disaster became a starting shot. The drug approval process was
      changed and new era of patient safety was initiated].

PMID- 22462270
TI  - [Living donor kidney transplantation--a successful story. Very cost-effective-
      and the donors live long with good health].

PMID- 22462271
TI  - [Malingering psychotic disorder--more common than psychiatrists want to believe.
      Four cases of malingering to gain benefits].

PMID- 22462272
TI  - [Higher risk for medical errors reporting following reorganizations in health
      care. The more reorganizations, the higher risk for physicians of being reported
      according to an inquiry].

PMID- 22462273
TI  - [The coordination health care-pharmacy is needed for good IT support. Patient
      safety is an important factor according to a pilot study from primary health care
      in Scania].

PMID- 22462274
TI  - [The picture of frontotemporal dementia is clearer. 25 years of research start to
      yield results].

PMID- 22462275
TI  - [Tranexamic acid after myocardial infarction. Referral to coagulation unit is
      recommended].

PMID- 22462276
TI  - [Swedish Andrological Society apropos the criticism of the testosterone campaign:
      men have righteous expectations for health care within andrology].

PMID- 22462277
TI  - [Scandinavian Surgical Outcomes Research Group (SSORG)--a new device for clinical
      studies].

PMID- 22462278
TI  - Health law in the 21st century.
AB  - INTRODUCTION: Law and health operate within different models affecting health
      law. AGEING POPULATION: Ageing and changed dynamics focuses health law on chronic
      illness, resource allocation, mobility and driving. SHRINKING PLANET: Swine Flu
      mandates health law to manage epidemiology, international travel and disease
      virulence. ACCESS TO HEALTHCARE: Population changes, doctors' numbers and
      remuneration, health insurance and demographics restrict healthcare access,
      impacting on health law. GENETICS: Genetic interpretation allows discrimination
      against undiagnosed people with genetic propensity to diseases, necessitating
      legal protection. COMPUTERS AND ELECTRONIC MEDICINE: E-medicine, telemedicine,
      record privacy and professional standards are relevant to health law. CONCLUSION:
      Issues concerning health law in the 21st century were reviewed.

PMID- 22462279
TI  - The one who chooses a country chooses its laws: health law and multicultural
      societies.
AB  - Health systems in Europe tangle with various cultural traditions and religious
      convictions and ethnic related specific health needs. Multicultural societies
      face health systems with challenges of human rights and values. When a person's
      right to freedom of religion comes into conflict with other interests of public
      health and the rights and freedoms of others, the freedom of religion might then
      be justifiably limited. Such limitation is a necessary means to be considerd
      under every democratic society; such limitations concerns a mechanism of
      proportionality as prescribed by law; yet does not constitute a discriminatory
      regime. To meet with health disparities between the non-western and the
      autochtonous groups of the population in multicultural societies, health systems
      must appropriately address the health needs of the different groups. To overcome
      present inequality in access for non-autochthonous groups of the population in
      multicultural societies, a paradigm shift from primary focus on the health of a
      rather homogenous Western population towards diversity in health needs is
      necessary.

PMID- 22462280
TI  - Legal action for the prevention of pandemics in China.
AB  - Pandemics still impose threats to human beings. Since the establishment of the
      People's Republic of China, (PRC) a series of laws and regulations have been
      written for the sake of preventing the spread of pandemics. This legislative
      process included drafting definitions and explanations of certain terms for the
      purpose of classification and administration, popularization, education and
      disease status reporting. The content of these regulations and laws has been
      enriched and refined constantly in accordance with the special features of the
      latest outbreak of pandemics. No one is exempted from these PRC regulations and
      laws on the Prevention and Treatment of Pandemics.

PMID- 22462281
TI  - Physician's error: medical or legal concept?
AB  - This article deals with the common term of different physician's errors that
      often happen in daily practice of health care. Author begins with the term of
      medical malpractice, defined broadly as practice of unjustified acts or failures
      to act upon the part of a physician or other health care professionals, which
      results in harm to the patient. It is a common term that includes many types of
      medical errors, especially physician's errors. The author also discusses the
      concept of physician's error in particular, which is understood no more in
      traditional way only as classic error in acting something manually wrong without
      necessary skills (medical concept), but as an error which violates patient's
      basic rights and which has its final legal consequence (legal concept). In every
      case the essential element of liability is to establish this error as a breach of
      the physician's duty. The first point to note is that the standard of procedure
      and the standard of due care against which the physician will be judged is not
      going to be that of the ordinary reasonable man who enjoys no medical expertise.
      The court's decision should give finale answer and legal qualification in each
      concrete case. The author's conclusion is that higher protection of human rights
      in the area of health equaly demands broader concept of physician's error with
      the accent to its legal subject matter.

PMID- 22462282
TI  - The divergence between scientific and legal approaches concerning the cause of
      effects of tobacco use under Spanish law.
AB  - When dealing with damages related to tobacco use, causation and its proof is one
      of the main aspects to take into account when victims--smokers and/or their
      families--try to claim compensation. In Spain, legal and scientific approaches to
      the problem seem to diverge. Scientific statements about the consequences of
      tobacco, which support the fight against this product worldwide, hardly serve
      plaintiffs' interests before courts, whose judgments oddly reveal an unusual
      tendency, in contradiction with principle pro damnato, that this article aims to
      briefly highlight.

PMID- 22462283
TI  - The legal protection of the medically examined applicant for insurance.
AB  - The private insurer needs information about the risk evaluation of the objective
      of the insurance. More specifically, in personal insurance he needs information
      about the insured person. To obtain such information he will often ask the
      applicant to undergo a medical examination. A crucial question is whether the
      medically examined applicant for insurance should be considered as a "patient",
      in which case he would enjoy the legally protected patient rights. As such, a
      medical examination is carried out at the request of the insurer, in view of
      concluding or carrying out a private insurance agreement. The applicability of
      several fundamental patient rights seems to be uncertain. His legal protection
      remains unsure. In this article, I firstly verify if the examined person is a
      patient. Then his protection as a patient will be examined. To conclude the
      alternative means to protect the medically examined applicant in the European
      context, as well as in other European member states, will be analyzed.

PMID- 22462284
TI  - Ethical dilemmas of Statutory Committees for involuntary hospitalization of
      mentally ill patients.
AB  - Mentally ill patients whose reality judgements are severely impaired by reason of
      their illness and consequently present a danger to themselves and others, may be
      involuntarily admitted to a secure psychiatric ward for the safety of both
      themselves and the public. The Israeli Statute for the Treatment of Mentally Ill
      Patients, enacted in 1955 and amended in 1991, sets out rules and procedures for
      such involuntary confinement, and grants authority to the MOH District
      Psychiatrist to issue initial involuntary admission orders. However, a patient
      can appeal a District Psychiatrist order before a judicial statutory committee,
      comprising two senior psychiatrists and a legal expert in the capacity of
      magistrate. Such committee is also the statutory forum for determining whether
      involuntary hospitalization should be extended. The committee may quite often
      face ethical dilemmas when, on the one hand, there is no question that the
      patient's judgement is severely impaired but on the other hand, his/her condition
      does not fully meet the criteria of the statutory requirements for involuntary
      confinement. This paper discusses the legal aspects and requirements of
      involuntary admissions vis-a-vis the ethical dilemmas that such Statutory
      Committees may face when deciding to extend hospitalization or to release the
      patient from committal. The paper shall also illustrate dilemmas actually brought
      before the Committee that have ended in a final ruling that balances moral
      ethical dilemmas with the strict statutory requirements.

PMID- 22462285
TI  - Ethics review of health research on human participants in South Africa.
AB  - In terms of South African legislation, all health research on human participants
      must be submitted to an accredited research ethics committee for independent
      ethics review. Health research covers a broad spectrum of research, including
      clinical trials. This article sets out the ethical-legal framework for the
      functioning and composition of such committees. It also deals with the newly
      created National Health Research Ethics Council, which registers and audits
      health research ethics committees. Special attention is given to the conduct of
      clinical trials. In conclusion, it is submitted that the National Health Act, the
      Draft Regulations Relating to Research on Human Subjects, and two sets of ethical
      guidelines adopted by the Department of Health provide a much needed and coherent
      ethical-legal framework for research in South Africa.

PMID- 22462286
TI  - Legal protection of informed consent of minors.
AB  - One of the pillars of healthcare provision is respect for the autonomy of the
      patient's wishes, which is given substance by the process of obtaining informed
      consent. Minors deserve special protection, entitled to basic rights and
      increasingly autonomous as they develop. In certain situations, minors are deemed
      matures and able to consent to treatment without the involvement of a parent or
      guardian. The assessment of competence would be based on the child's functional
      ability, not on age or outcome of the decision. This manuscript includes a brief
      analysis of legal perspectives on informed consent of minors, and minors'
      capacities to make medical decisions. Remaining questions of how to evaluate
      capacity and balance parental and minor autonomy are explored. Considerations on
      informed consent in different situations as refusing treatment and termination of
      pregnancy by female children are analyzed.

PMID- 22462287
TI  - The physician's right to conscientious objection: an evolving recognition in
      Europe.
AB  - Due to the growing number of medical treatments, physicians--who are also human
      beings with their own conscience and beliefs--are increasingly confronted with
      treatments that may conflict with their principles and convictions. Although
      several human rights documents recognize the freedom of conscience and belief, we
      could not locate the recognition of an explicit right to conscientious objection.
      Furthermore, a direct application of the right to freedom of thought, conscience
      and religion, as recognized by article 9 of the ECHR, does not include such a
      right due to the narrow interpretation of this right by the European Court of
      Human Rights. However, the Court seems to have taken steps away from this narrow
      interpretation in Pichon and Sajous v. France. Notwithstanding these steps, no
      general right to conscientious objection exists. Physicians therefore are
      dependent on a judgment if they refuse a certain treatment because of
      conscientious objections.

PMID- 22462288
TI  - Patients' rights a case for a Charter of Participant Rights in Pre-Market Drug
      Trials: the next evolution.
AB  - Since the first publication of Medicine and Law thirty years ago, there have been
      significant international advances in patient rights and participant protections
      in clinical trials. Despite such advances, there are still alarming reports of
      actual or perceived breaches in ethical standards by Institutions, Investigators
      and Sponsors of pre-market drug clinical trials. This is particularly disturbing
      as these trials involve participants in the testing of an investigational drug
      before its full safety, effectiveness, and clinical outcomes are understood.
      Moreover, the study design may randomize participants (recruited because they
      have specific diseases or conditions) into a group receiving a placebo or
      comparator drug versus a group receiving the investigational drug. The proposed
      Charter of Participant Rights in Pre-Market Drug Trials reflects the growing
      trend towards a participant-centred approach to the implementation and
      enforcement of participant rights. The development and adoption of the Charter is
      the next natural step towards the guarantee of rights in pre-market clinical drug
      trials.

PMID- 22462289
TI  - Advance treatment directive: a tool for dialogue or self-protection in the
      physician-patient relation?
AB  - The authors intend to assess the efficacy of the advance treatment directive as a
      tool for involving patients into the decision-making process and the actual
      implementation of the physician-patient communication. It seems particularly
      appropriate to distinguish between "generic" advance directive, happening outside
      of the physician-patient relation, and documents drafted with the assistance of
      care providers, in the context of such an information and communication process.
      That is, in order to guarantee the awareness of patients and the pertinence of
      the disclosed indication to the current situation with reference to the subject
      matter of advance treatment directive. In addition, considering the different
      ways for the will of a patient to be conveyed--written statements, unexpressed
      will reported by witnesses, expressed will in an intelligible way by patients
      with severe verbal communication deficit--it is deemed important to identify the
      formal requirements for the validity of the above expressions of will. From an
      ethical standpoint, if we transcend a merely contract-centred and defensive
      vision of the physician/patient relation, the positive meaning of autonomy lays
      in its effective enforcement in the decision-making and care processes, with
      regard to the defined circumstances and the specific objects it refers to.
      Physician/patient communication means, for the purposes of this discussion, a
      preferential tool to balance the substantially asymmetrical relation between a
      physician and a patient: the process is based on a path of mutual recognition
      where the formal protection of each other's scopes of competency and right to
      self-determination stand for an essential requisite, though only preliminarily,
      to the actual accomplishment of consent in its cognitive and practical features.

PMID- 22462290
TI  - Factors associated with child witnessing of intimate partner violence in Canada.
AB  - Knowing the characteristics associated with child exposure to spousal abuse could
      aid in early identification of at-risk children. The purpose of our study is to
      determine possible factors associated with child witnessing of intimate partner
      violence (IPV) in Canada using data from the 1999 General Social Survey, a
      representative telephone survey of Canadians aged 15 years and older. Respondents
      reporting IPV in the five years prior to the survey were asked whether a child
      had witnessed the incident. Multivariate logistic regression was used to
      determine the association between child witnessing of IPV and victim, assault,
      and help-seeking characteristics. Households in which child witnessing of IPV was
      reported were distinguished by the following factors: female respondent, visible
      minority, over age 30, separated, divorced, or widowed, low income, and the
      presence of children aged 0-14 years. Other significant variables associated with
      child witnessing of IPV were related to the frequency, reporting, and disclosure
      of violent incidents.

PMID- 22462291
TI  - Management of conflicts with the parents over administration of life-prolonging
      treatment in Dutch NICUs.
AB  - In the Neonatal Intensive Care Unit (NICU) setting, the patient's parents and the
      medical team dispute sometimes over the administration of life-prolonging
      treatment to be provided to the patient. This article focuses on the situation
      where the parents insist on the treatment, whereas the doctors are of the opinion
      that the prospects for the future of the baby are too poor to justify (further)
      artificial prolongation of life. The article provides an informative background
      on the regulation of the decision-making process in relations with the
      administration of life-prolonging treatment in Dutch neonatology. It also
      presents the results of a set of interviews with Dutch neonatologists. These
      results suggest that the doctors are very inclined to take the parents'
      preferences into account.

PMID- 22462292
TI  - [Family perceptions and moderating factors of involvement in non-residential
      fathers].
AB  - The involvement of non-resident fathers with their child was analysed by use of a
      questionnaire in a sample of 74 divorced or separated families living in the city
      of Ziurich, Switzerland. Fathers, mothers, and one child separately rated the
      involvement of the father. The three perspectives were compared and showed
      significant differences in the dimensions of educational responsibility,
      cognitive and social support, and the quality of the emotional relationship. The
      temporal availability and leisure time activities did not show significant
      differences. The different family perspectives should be considered when
      assessing a father's involvement with his child. The quality of the relationship
      of the children to their fathers was primarily fostered by the emotional
      engagement of the father.

PMID- 22462293
TI  - [Childhood temperament and maternal affectivity].
AB  - This study examines the question whether early childhood temperaments of children
      of mothers suffering from postnatal depression differs from children of non
      depressed mothers. Children of clinically depressed mothers were assessed with
      regard to their temperament on two different dimensions and compared to a control
      group. The level of cortisol concentration in the children's saliva was the first
      variable. Saliva samples were gathered on three consecutive days to obtain a
      baseline, and before and after a mother-children interaction, which was
      interrupted by a still-face phase. As second variable the early childhood
      temperament was assessed with the Infant Behavior Questionnaire (IBQ). After the
      mother-children interaction the cortisol concentration levels of children of
      mothers suffering from postnatal depression were significantly lower. In the IBQ
      Scales the children of depressed mothers showed significantly higher values on
      the scales Distress to Limitations and Activity. The significantly lower cortisol
      concentration in the saliva of children of mothers suffering from postpartum
      depression could be an indication that these children are already used to the
      fact that their mothers are not paying attention to them during the still-face
      phase. Overall, the results give rise to the assumption that postpartum
      depression does have an adverse impact on the development of affected children
      and that early intervention would be expedient to prevent the occurrence of
      pathological behavior characteristics and difficult mother-child relationships.

PMID- 22462294
TI  - [Applicability of the SON-R 6-40 in children with hearing impairment and children
      with diverse cultural and language backgrounds].
AB  - Certain aspects of the use of the Snijders-Oomen Non-verbal Intelligence Test
      (SON-R 6-40) in clinical and educational assessment of children with hearing
      impairment and children from immigrant families are discussed. Test results of 35
      children per group have been compared to the data from a German-speaking control
      group, matched by age, sex and educational achievement of both parents. Specific
      differences between the three groups on both subtest and IQ levels are
      demonstrated. This paper provides scoring results for the three groups and
      discusses the differences between the test profiles. The test can be accomplished
      with children who have special educational needs. Results also prove the
      usefulness of a non verbal test in the assessment of cognitive abilities in
      clinical-diagnostic questions.

PMID- 22462295
TI  - [Working verbally and non-verbally within the psychotherapeutic process].
AB  - Patients in paediatric and adolescent psychiatry frequently suffer from both a
      categorical psychiatric disorder and structural deficits. Within the scope of a
      competence profile--which is subdivided into three areas: knowledge, skills, and
      a method--this article describes the term "structure" as used in the
      Operationalised Psychodynamic Diagnostics for Children and Adolescents (German
      abbreviation: OPD-KJ) as well as the deficits of self-esteem regulation. In this
      context, the development and importance of affects and their regulation for, as
      well as within, the therapeutic relationship are discussed, including the bodily
      processes associated with them. Finally, the article demonstrates how we as
      practitioners in the areas of therapeutic mental health and education can
      compensate for structural deficits of our patients by using our knowledge of
      psychological structures and of affect regulation and its importance for the
      therapeutic process; we can also use our own structural competences and
      competences to perceive the patients' affects as revealed by their bodies. For
      this purpose, we introduce methods that include body-psychotherapeutic
      interventions, among others.

PMID- 22462296
TI  - Health insurance is for everyone. It's the only way to deliver lower-cost health
      care--with better results.

PMID- 22462297
TI  - What counts as crazy? This is the book doctors use to define mental illness--and
      it's all about to change.

PMID- 22462298
TI  - Blue Ivy league. Beyonce and the need for more celebrities who breast-feed.

PMID- 22462299
TI  - Getting up to speed. Execs detail IT needs, investments required to support an
      ACO.
AB  - The push for accountable care organizations means a push for more information
      technology that allows the sharing of data. So hospitals and other providers that
      are forming ACOs are feeling new urgency to ramp up their IT improvements. At
      Banner Health it means figuring out how to deal with independent physicians'
      "mishmash" of systems. "There has been an acceleration of interest," says Dr.
      John Hensing, left, Banner's chief medical officer.

PMID- 22462300
TI  - More time, more questions. IT groups criticize postponement of ICD-10 deadline.

PMID- 22462301
TI  - Policing overpayments. Rule would give force to worker allegations.

PMID- 22462302
TI  - Healthcare's waffle house. Resolute leadership is becoming difficult to find in
      healthcare circles these days.

PMID- 22462303
TI  - A meaningful year. The new year brings continued health IT challenges.

PMID- 22462304
TI  - Rules of the road. Annual survey highlights execs' priorities as they try to
      steer through the shifting regulatory landscape for healthcare IT.

PMID- 22462305
TI  - Remodeling required? Medical-home demos advance, but questions persist over
      performance data.

PMID- 22462306
TI  - Early decision. Will new advances in prenatal testing shrink the ranks of babies
      with Down syndrome?

PMID- 22462307
TI  - After all, everybody loves a good story! Update on the case reports' chronicle.

PMID- 22462308
TI  - Advanced COPD patients under home mechanical ventilation and/or long term oxygen
      therapy: Italian healthcare costs.
AB  - BACKGROUND AND AIM: Little information is available on healthcare costs for
      patients with very severe chronic obstructive pulmonary disease. The aim of the
      current work was to evaluate Italian healthcare costs in these patients. METHODS:
      Prospective 1-year analysis was assessed in three subgroups of patients; non
      invasively ventilated (n=30); invasively-ventilated (n=12) and on long-term
      oxygen therapy (n=41). Acute costs for care were a sum of fees for doctor's
      consultations, admissions to hospital (ward and intensive care units) and
      emergency drugs. Chronic costs were the sum of costs for pharmacotherapy and home
      ventilation and/or oxygen care. RESULTS: Mean cost/day/patient was 96 +/- 112
      Euro (range 9-526 Euro), with acute costs accounting for 72% and chronic costs
      for 28% of the total cost burden, with no significant differences in costs
      associated with the three subgroups. Acute costs had a non-normal distribution
      (range 0 to 510 Euro) being cost for hospitalisation the highest cost burden with
      more than 30% of acute care costs attributed to only a small segment of patients.
      Chronic care costs were also unevenly distributed among the various groups (ANOVA
      p = 0.006), being home oxygen supply the highest cost burden. CONCLUSIONS: The
      current Health Care System is in urgent need for a reassessment of the high cost
      burden associated with hospitalisations and home oxygen supply.

PMID- 22462309
TI  - The effect of antituberculosis treatment on interferon-gamma release assay
      results.
AB  - BACKGROUND AND AIM: Monitoring the efficacy of antituberculosis therapy is
      crucial. The aim of this work is to investigate the effect of tuberculosis
      treatment on interferon-gamma response using Quanti-FERON-TB Gold in tube (QFT
      GIT). METHODS: A total of 216 new pulmonary tuberculosis (TB) cases were tested
      with QFT-GIT at the start of the treatment and, randomly, once or twice between
      90 and 180 days afterwards. Data was analysed using the random effect regression
      model analysis. RESULTS: 63.4% of patients were positive at the QFT-GIT (> .35 UI
      cut-off). TB cases showed a significant log-linear increase in interferon-gamma
      (IFN-gamma) concentration, over time of treatment: IFN-gamma concentration
      increased by 78% after 6 months of treatment in acid-fast bacilli positive (A)
      and culture negative cases in culture confirmed cases the increase was 43% if A+
      and 20% in A-. CONCLUSIONS: Effective therapy seems to restore cellular responses
      to Mycobacterium tuberculosis antigens. The potential use of interferon gamma
      release assay (IGRA) in monitoring response to TB treatment is hampered by the
      presence of active mycobacterial replication at baseline and needs further
      evaluation.

PMID- 22462310
TI  - Combined pulmonary fibrosis and emphysema syndrome: a radiologic perspective.
AB  - Chronic obstructive pulmonary disease (that includes emphysema) results in
      significant morbidity and mortality worldwide. Idiopathic pulmonary fibrosis
      (IPF) is also a chronic and progressive parenchymal lung disease with an average
      survival of less than 5 years after diagnosis. Combined pulmonary fibrosis and
      emphysema (CPFE) is an important but still underdiagnosed syndrome. Its diagnosis
      is based on the radiological findings at computed tomography which consists of
      emphysema of the upper lung zones and fibrosis of the lower lung zones. Since
      this syndrome has a very bad prognosis, even worse than isolated finding of
      emphysema or fibrosis alone, early recognition and rapid treatment are important.
      In this article we will review and elucidate the radiologic appearance of this
      syndrome and highlight its clinical importance.

PMID- 22462311
TI  - Adult-onset pulmonary involvement in Niemann-Pick disease type B.
AB  - Niemann-Pick disease type B is caused by a deficiency in acid sphingomyelinase
      activity; among the six variants of Niemann-Pick disease known to date, it is the
      most frequently associated with lung involvement, a major cause of morbidity and
      mortality in this subtype in patients of all ages. Nevertheless, the vast
      majority of reports in the literature concern infantile forms, while less
      reported is, for several reasons, the onset in adults being consequently still
      poorly understood and characterized its clinical, radiographic and functional
      manifestations. We report a case of a 37 years-old female patient affected by
      subtype B since she was an infant, operated for aortic valve replacement two
      years before and came to our attention for the onset of a worsening exertional
      dyspnoea which proved, through a series of functional tests and radiological
      exams, to be a consequence of the diffuse lung involvement by the metabolic
      disorder; we performed a review on this topic through a Medline search of all the
      available "adult-onset" case reports published since the first description in
      1964, also considering the possible association between NPDB and, more generally
      lysosomal storage disorders, and the valvular disease, already suggested by
      several Authors in previous works.

PMID- 22462312
TI  - Cardiovocal syndrome.

PMID- 22462313
TI  - Large pulmonary hamartoma with "popcorn" like calcification.

PMID- 22462314
TI  - Medical strain. CDC report: bills present hardship to families with and without
      insurance.

PMID- 22462315
TI  - Growing pains. Insurers and PbMs want in on 340B savings.

PMID- 22462316
TI  - Negative outcome. Study brings CMS website impact into question.

PMID- 22462317
TI  - Greater expectations. Keeping docs means changing incentives.

PMID- 22462318
TI  - Role model. Tax exemptions in Ill. may have impact elsewhere.

PMID- 22462320
TI  - Re-sizing. Annual Construction & Design Survey shows continued pickup in
      projects, with many going forward on a smaller scale.

PMID- 22462319
TI  - Moderately hopeful. Unbending partisanship won't help solve problems facing the
      nation.

PMID- 22462321
TI  - Secrecy hampers. Congress needs to act to increase medical-device transparency.

PMID- 22462322
TI  - No fix needed. Price transparency for medical devices a nonsolution for a
      nonproblem.

PMID- 22462323
TI  - Shortchanged exchange. Lack of incentives leaves many facilities unplugged.

PMID- 22462324
TI  - The use of virtual reality for carotid artery stenting (CAS) training in type I
      and type III aortic arches.
AB  - AIM: Simulation has been proposed to improve learning curves in carotid artery
      stenting (CAS), but previous studies have only evaluated CAS simulation in a
      single type of arch usually either type I or type II. The aim of our study is to
      define the use of virtual reality for CAS training in type I and type III aortic
      arches for novice operators. MATERIALS AND METHODS: Fifty experienced
      interventionalists and fifty novice trainees with no prior experience with
      endovascular procedures performed a virtual CAS in a type I aortic arch case and
      one in a type III arch case. They trained on simulator for two hours and then
      repeated the procedures. Data of the procedures were collected and analysed.
      RESULTS: Among novice operators, 38 out of 50 ended the first procedure on type I
      arch (76%) and 32% (16 out of 50) concluded the first procedure on type III arch
      (p < .05). After training, 100% of novice ended the easy case and 56% (28 out of
      50) concluded the difficult case (p < .05). All experienced operators
      successfully carried out the simulations. The simulator induced greater
      improvement among novice in type I arch rather than in type III arch.
      Performances of experienced didn't improve significantly. Among novice, virtual
      performances of "difficult" cases were significantly worse than those of "easy"
      cases, both before and after training. CONCLUSIONS: Simulator is an effective
      tool for training of novice operators in type I aortic arch; on the contrary its
      role has yet to be established in type III aortic arch.

PMID- 22462325
TI  - Bilateral lung lesions: when the eyes deceive the brain!
AB  - We report a clinic case of patient in whom angiosarcoma of the heart presents as
      bilateral pulmonary nodular infiltrates. The cardiac tumor was clinically silent,
      the electrocardiogram was normal and the cough was the only symptom. Chest CT
      scan (Fig. 1) showed bilateral diffuse nodular infiltrates ranging. Clinical
      clues, the results of laboratory tests and all of the cultures obtained excluded
      an infectious etiologies; the findings of CT-guided needle biopsy was
      inconclusive for a definitive diagnosis. Thus, the patient was scheduled for a
      thoracoscopic biopsy. Surprisingly, the pre-operatory echocardiogram showed a
      soft tissue mass fixed to the posterior wall of the right atrium. On
      retrospective reviewing of chest CT scan, a tumor was evident in the right
      atrium, but it was missed initially. In theory, the lung lesions attract the
      attention of the observer who had not taken into account anything else as to say:
      "the brain knows what the eyes want". The diagnosis ofpulmonary metastases was
      obtained by means ofpleural biopsy during right thoracoscopy. Immunoistochemical
      staining revealed a CK-, CK7-, EMA-, ESA-, CEA-, TTF1-, Vimentina+, CD31+, CD117+
      lesion. Because at the time of diagnosis our patient already had lung metastases,
      he underwent chemotherapy.

PMID- 22462326
TI  - Nerve sparing sutureless total thyroidectomy. Preliminary study.
AB  - AIM: In the present study the authors assess the advantages of new technologies
      in thyroid surgery: to prevent nerve injury by using an intra-operative
      continuous nerve-monitoring techniques and to compare the real advantages of
      advanced coagulation devices. MATERIALS AND METHODS: Among a series of 440
      thyroidectomies (jan 2004-feb 2006) the Authors reviewed charts from two groups:
      (1) 240 total thyroidectomies performed using the traditional monopolar
      electrocautery, non-absorbable stitches for the principal vascular pedicles. (2)
      140 total thyroidectomies performed using dedicated small bipolar electro thermal
      coagulator (ligasure-precise). (3) Since 2006 in a double blind group selection
      of 70, we've performed sutureless thyroidectomy with continuous intraoperative
      nerve monitoring using dedicated endotracheal tube. Mean operative time, post
      operative bleeding, post-operative stay, incidence of transient or definitive
      laryngeal nerve lesions, incidence of permanent or transient hypocalcaemia, costs
      of the procedures were analyzed. RESULTS: Major complications in the first two
      groups compared with the data of the literature are absolutely over-imposable,
      except a reduction of incidence of transient hypocalcaemia in the Precise group,
      but if we compare data of the 3rd group (NIM), we find a significative reduction
      of transient and permanent laryngeal nerve palsy incidence. DISCUSSION AND
      CONCLUSION: This new technology offers several advantages: (1) atraumatic; (2)
      easy to use; (3) continuous monitoring and audio feedback to the surgeon (4)
      works outside the operation field (5) high sensitiveness. Cost-analysis confirm
      that NIM + ligasure have same or less cost and time and probably less
      complications than traditional Total Thyroidectomy.

PMID- 22462327
TI  - [Thyroidectomy using the intra-operative neuromonitoring and the surgeon's
      confidence].
AB  - AIM: Reporting our experience with NIM-response 2.0 and 3.0 system in a series of
      127 thyroidectomies. MATERIALS OF STUDY: 127 patients were operated at the "Magna
      Graecia" University (Catanzaro) from 2009 September to 2010 December, using the
      technique of IntraOperative NeuroMonitoring (IONM). For each patient the surgeon
      charge filled in a "questionnaire" assessing his/her compliance with the
      apparatus. RESULTS: We report 0.8% permanent and 0.4% transient recurrent
      laryngeal nerve paralysis. All surgeons have been fully satisfied from IONM
      technique. DISCUSSION: A recurrent laryngeal nerve lesion may occur in patients
      operated on total thyroidectomy between 5-8% for transient palsies and 1-3% for
      the permanent ones. The use of IONM seems to contribute to a reduction of
      transient paralysis, even if this method is still not widely accepted
      Nevertheless the compliance of the surgeons with IONM seems to develop very
      highly. CONCLUSIONS: NIM-response is helpful in protecting recurrent laryngeal
      nerve function. Advantages were observed in reduction of postoperative dysphonia
      and in improving the surgeon's confidence in performing a total thyroidectomy.

PMID- 22462328
TI  - [Neuromodulation in the treatment of hand's scars].
AB  - AIM: In the present study, we investigated effects of a local anesthetic, in the
      treatment of pathologic scars. MATERIALS AND METHODS: this retrospective report
      describes our experience with 97 patients who underwent lidocaine 2% injections
      in surgical scars of the hand. The results were evaluated using 4 parameters:
      cutaneous structure, pain, thikness and colour of the scar. RESULTS: The mean
      outcome was the pain control. 2 out of 97 showed a 100% improvement in all the
      parameters. In 95 of 97 patients the improvement was between 60-100%. DISCUSSION:
      Lidocaine controls different pathways of inflammation. Flogosis is the first
      phase of cicatrization and so lidocaine could be used in the treatment of
      pathologic scars. A previous study confirms the role of lidocaine, injected to
      control the pillar pain in the carpal tunnel's surgery in the improvement of
      scars. CONCLUSION: Lidocaine, as neuromodulation treatment, acts on inflammation,
      temperature, perfusion and partial pressure of oxygen.

PMID- 22462329
TI  - [Polythelia and supernumerary breast. Personal experience and review of the
      literature].
AB  - AIM: Our study focuses on the approach, management and treatment of patients with
      polythelia and supernumerary breast and the target is the search for a treatment
      algorithm for these diseases. MATERIAL OF STUDY: We considered at 18 patients
      treated from 2006 to 2011 for breast congenital anomalies in excess. 14 surgical
      procedures were performed, 8 for supernumerary nipple excision (1 case associated
      with Poland Syndrome) and 6 for accessory breast ablation. All patients were aged
      between 15 and 34 years and belonged to both sexes. RESULTS: The breast tissue it
      was detected fibrocystic mastopathy in 5 cases of polimastia. In the remaining
      cases the nipples and mammary tissues were normal. After a median follow-up from
      one to five years, we obtained in all cases not only an excellent aesthetic
      result but also a psychological. DISCUSSION: The supernumerary breast tissue is
      not just a cosmetic problem, it is also subject to the same pathological lesions
      that are observed in a normal breast. In view of the potential malignant
      transformation of anomalous breast incidentally, early and accurate diagnosis is
      required as well as its monitoring over time. CONCLUSIONS. We therefore believe
      that surgical approach is always necessary in cases of polimastia, while
      considering options in the treatment of polythelia, where it becomes crucial if
      aesthetic and/or psychologically problems in the patient coexist.

PMID- 22462330
TI  - Laparoscopic treatment of chronic slow transit constipation. Report of three
      cases and review of literature.
AB  - INTRODUCTION: The Authors present their experience with laparoscopic total or
      subtotal colectomy (TC or SC) in three patients operated for intractable chronic
      slow transit constipation (STC), together with a review of literature. MATERIAL
      AND METHODS: From July 2005 to July 2009 three young patients affected by STC,
      after meticulous preoperative instrumental work-up and after failure of medical
      treatment, were submitted to laparoscopic TC and ideo rectal anastomosis (IRA) in
      two cases and to laparo assisted SC followed by Ceco Rectal Anastomosis (CRA) in
      one case. Number of daily bowel motions, urgency soiling, incontinence, abdominal
      pain, bloating with special regard to patient's quality of life, were analyzed.
      RESULTS: All the interventions were completed via laparoscopic approach. No
      postoperative morbidity or mortality were observed. After twelve months, the
      patients referred two-three daily evacuation of soft stool, with a good
      continence and disappearance of abdominal pain and other relatives symptoms. They
      reported excellent satisfaction with the surgical results and a significant
      improvement of their quality of life. DISCUSSION: TC with IRA and CRA after SC
      represent the most effective and widely used surgical operations in the treatment
      of STC, in well selected patients, after failure of conservative treatment.
      According to Literature data, and in our experience, no significant differences
      in terms of postoperative morbidity or mortality neither in quality of life were
      observed between the two operations. It is well demonstrated the feasibility of
      the laparoscopic approach in treatment of colorectal pathologies with typically
      advantages of less invasive surgery, respect of parietal integrity, less
      postoperative pain and ileus, fewer postoperative adhesions, a reduced
      hospitalisation and finally a better cosmesis. CONCLUSIONS: Laparoscopic TC and
      IRA and CRA after laparo assisted SC represent efficacious operations in the
      treatment of STC offering a good postoperative quality of life and reduced
      morbidity compared to open surgery.

PMID- 22462331
TI  - The sentinel lymph node: a suitable technique in breast cancer treatment?
AB  - AIM: The sentinel lymph node biopsy (SLNB) was firstly introduced by Giuliano and
      co. in 1994 for the treatment of breast cancer; in comparison to the axillary
      lymph node dissection (ALND), the sentinel lymph node biopsy has shown both a
      lower morbidity and acceptable distance results. We want to show that this
      technique is reliable and should be used routinely in selected cases. MATERIALS
      OF STUDY: The study on the sentinel lymph node has been carried out, prior
      informed consent, in 128 patients aged between 27 and 80 years and suffering from
      non-multicentric infiltrating breast carcinoma, with a diameter not greater than
      3 cm, clinically negative axillary, and hospitalized from January 1998 to
      September 2005 at the Department of Gerontology, Geriatrics and Metabolic
      Diseases of the Second University of the Study of Naples. For the recruitment of
      patients subjected to the sentinel lymph node research study, we have respected
      the inclusion criteria. RESULTS: Histological examination of the tumor revealed
      95 cases of ductal carcinoma, 16 cases of mucinus carcinoma, 13 of lobular
      carcinoma and 4 of medullary carcinoma. The sentinel lymph node was detected
      through lymphoscintigraphy in 96.9% of the cases (124 patients), whereas it was
      not possible to identify it in 4 patients (3.1% of the cases), 2 of which had
      previously been subject to excision biopsy. DISCUSSION: The SLNB is characterized
      by an identification rate of SLN > 90% with a false negative rate less than 5%.
      In our study we have found an SLN identification rate of 96.9% with false
      negative rates of 3.9%. Our data show that in only 6,3% of the patients (4 non-
      identified and 4 false-negative cases) it was necessary to perform ALND because
      the SLN resulted positive; however no metastasis were observed in level III lymph
      nodes. CONCLUSIONS: Since its inception, the sentinel lymph node technique has
      gained an increasingly important role in the conservative treatment of the breast
      carcinoma due to the short duration of the surgery, the decrease of post
      operative pain, the risk of lymphedema onset and hospital confinement, the high
      predictive power and the diagnostic accuracy. We strongly believe that the
      sentinel lymph node technique is reliable and should be used routinely in
      selected cases.

PMID- 22462332
TI  - Reconstruction of the loss of substance of the dorsum of the hand: from the
      conventional techniques to regenerative surgery procedures.
AB  - AIM: Our aim is focused on the advantages of new technologies compared with those
      of traditional methods in the reconstruction of the loss of substance of the
      dorsum of the hand. MATERIAL OF STUDY: We observed 37 patients from 2007 to 2010
      with loss of substance of the dorsum of the hand, also associated with
      significant comorbidities. In 27 patients we chose surgical reconstruction, in 10
      patients we opted for conservative reconstruction with the use of new
      technologies. RESULTS: After a median follow-up from one to three years, in all
      cases the skin coverage was reinstated and mobility was restored, thereby
      adhering to the principles of both morphological and functional reconstruction.
      DISCUSSION: Concerning reconstruction by means of flaps, the main principles
      dictate is the new coverage must appear as much as possible, similar to the
      original tissue. The reconstruction must be in a single surgical time. On the
      other hand, the advent of advanced dressings and bioengineering has optimized
      conservative skin repair. CONCLUSIONS: We have seen a considerable broadening of
      the indications for conservative reconstruction. This method is suitable for
      reconstruction of the dorsum of the hand with good effectiveness, it makes it
      possible to obtain a tissue of good quality, which is flexible and smooth on the
      tendons and is not excessively thick. These methods are achieved with relative
      ease even in patients with poor general health. Although costly, this procedure
      will ultimately save the patient from further surgeries and hospitalization
      expenses, making it advantageous when considering the benefit-cost ratio.

PMID- 22462333
TI  - Conventional (CH) vs. stapled hemorrhoidectomy (SH) in surgical treatment of
      hemorrhoids. Ten years experience.
AB  - INTRODUCTION: Interest about hemorrhoids is related to its high incidence and
      elevated social costs that derive from its treatment. Several comparative studies
      are reported in Literature to define a standard for ideal treatment of
      hemorrhoidal disease. Radical surgery is the only therapeutic option in case of
      III and IV stage haemorrhoids. Hemorrhoids surgical techniques are classified as
      Open, Closed and Stapled ones. OBJECTIVE: We report our decennial experience on
      surgical treatment focusing on early, middle and late complications, indications
      and contraindications, satisfaction level of each surgical procedure for
      hemorrhoids. METHODS: Four hundred forty-eight patients have been hospitalized in
      our department fom 1st January to 31st December 2008. Of these 241 underwent
      surgery with traditional open or closed technique and 207 with the SH technique
      according to Longo. This retrospective study includes only patients with
      symptomatic hemorrhoids at III or IV stage. RESULTS: There were no differences
      between CH and SH about both pre and post surgery hospitalization and
      intraoperative length. Pain is the most frequently observed early complication
      with a statistically significant difference in favour of SH. We obtain good
      results in CH group using anoderma sparing and perianal anaesthetic infiltration
      at the end of the surgery. In all cases, pain relief was obtained only with
      standard analgesic drugs (NSAIDs). We also observed that pain level influences
      the outcome after surgical treatment. No chronic pain cases were observed in both
      groups. Bleeding is another relevant early complication in particular after SH:
      we reported 2 cases of immediate surgical reintenvention and 2 cases treated with
      blood transfusion. Only in SH group we report also 5 cases of thrombosis of
      external haemorrhoids and 7 perianal hematoma both solved with medical therapy
      There were no statistical significant differences between two groups about fever,
      incontinence to flatus, urinary retention, fecal incontinence, substenosis and
      anal burning. No cases of anal stenosis were observed. About late complications,
      most frequently observed were rectal prolapse and hemorrhoidal recurrence,
      especially after SH. DISCUSSION AND CONCLUSION: Our experience confirms the
      validity of both CH and SH. Failure may be related to wrong surgical indication
      or technical execution. Certainly CH procedure is more invasive and slightly more
      painfull in immediate postoperative period than SH surgery, which is slightly
      more expensive and has more complications. In our opinion the high risk of
      possible early and immediate complications after surgery requires at least a 24
      hours hospitalization length. SH is the gold standard for III grade haemorrhoids
      with mucous prolapse while CH is suggested in IV grade cases. Hemorrhoidal
      arterial ligation operation (HALO) technique in III and IV degree needs further
      validations.

PMID- 22462334
TI  - [Treatment of ulcer and difficult wounds of the lower limbs: our experience].
AB  - AIM: The purpose of this study is to evaluate the results obtained using
      traditional and advanced dressings, platelet gel, vacuum therapy and surgical
      techniques (grafts, flaps and dermal substitutes) in the treatment of ulcers and
      difficult wounds of the lower limbs to determine a treatment algorithm. MATERIAL
      OF STUDY: From January 2006 to September 2010 were performed 428 treatments on
      377 patients (203 men and 174 women, age between 32 and 90 years). Both medical
      and surgical treatments were performed: 61 traditional medications, 149 advanced
      dressings, 25 with platelet gel, 42 with the vacuum therapy, 16 with surgical
      debridement, 86 with skin grafts of varying thickness, 8 with dermal substitutes
      and 42 with surgical flaps. RESULTS: The best results were obtained with the most
      innovative methods, which showed, on average, a higher healing rate compared to
      traditional medications. Positive results were also obtained with surgical
      treatment if properly preceded by a correct wound bed preparation. CONCLUSION:
      The main characteristic that should guide the choice of therapy is the clinical
      appearance of the lesion: correct management of all its aspects allows to
      increase the rate of healing and, when necessary to have recourse to less
      invasive surgical procedures.

PMID- 22462335
TI  - Prevention of bacterial translocation using glutamine and melatonin in small
      bowel ischemia and reperfusion in rats.
AB  - BACKGROUND: Ischemia/reperfusion (IR) injury of the intestine is a major problem
      in abdominal pathological condition and is associated with a high morbidity and
      mortality. The purpose of the study is to determine whether glutamine and
      melatonin can prevent BT of small intestinal IR injury in rats. METHODS: Forty
      Wistar-albino rats with a weight of 200 to 250 g were used in the study. They
      were randomly divided into four groups (n=10 for each group): sham operated group
      (Group I), IR group (Group II), IR+ glutamine treatment group (Group III) and IR+
      melatonin treatment group (Group IV). All animals were given 10(10) E. Coli by
      orogastric intubation 12 hours before sampling. Seventy-two hours after the first
      operation, mesenteric lymph node and blood samples were obtained and cultured Two
      cc blood samples were obtained for a Polymerase chain reaction study. A piece of
      terminal ileum was also sampled for histopathologic examination. RESULTS:
      Mesenteric lymph node and blood cultures of all control animals were positive for
      microbiological growth, and polymerase chain reaction results were positive in
      seven of the eight rats. Histopathologically, edema, vasodilatation and
      inflammatory cell infiltration were found to be less in the other groups in
      comparison to the control group. The incidence of bacterial translocation was
      decreased in all treatment groups as compared to the control group. CONCLUSIONS:
      Glutamine and Melatonin reduced the incidence of BT in intestinal I/R. rats.
      These results suggest that glutamine and melatonin would be clinically useful in
      the treatment of intestinal I/R injury.

PMID- 22462336
TI  - Brachial thrombosis in a premature neonate. A case report.
AB  - Arterial injuries in infants are rare and in most cases are of iatrogenic origin
      as a consequence of catheterization, venipuncture or arterial blood sampling.
      These lesions require an accurate, noninvasive clinical diagnosis and prompt
      exploration and reconstruction using microvascular techniques to restore
      perfusion and to avoid morbidity and even mortality. We present a 3-day-old
      infant with a brachial artery thrombosis by a white thrombus as a consequence of
      an unsuccessful attempt to introduce an intravascular catheter. A microvascular
      reconstruction was performed, with complete restoration of the blood flow. Any
      suspected vascular injury needs immediate clinical and diagnostic assessment in
      order to avoid potential life-threatening complications. Surgery is mandatory in
      case of extensive arterial injuries, in case of inadequate distal blood supply or
      in case of progressive worsening of ischemic clinical findings.

PMID- 22462337
TI  - [Chilaidity syndrome. Case report].
AB  - Chilaidity syndrome is a mal position by bowel mal rotation o malfissation. It is
      more common in right side expecially in obese people. If asyimptomatic, the
      syndrome is an occasional comparison by radiology, surgical exploration by
      laparoscopy or autopsy, otherwise, if symptomatic, there are obstructive
      symptoms,abdominal pain, nausea, vomiting, abdominal distension, flatulence,
      breath, constipation and anorexia. Diagnosis is radiological. We present a rare
      case of this syndrome in a man with serious obstructive symptoms.

PMID- 22462338
TI  - About a case of squamous cell carcinoma of the scalp. Management and aesthetic
      results.
AB  - We present a case of squamous cell carcinoma of the scalp, treated with local
      excision and flap reconstruction. We discuss the treatment modalities of this
      pathology with particular attention to the role of surgery and adjuvant
      radiotherapy. The authors suggest the systematic use of subgaleal drainage to
      avoid the hematoma and/or seroma occurrence.

PMID- 22462339
TI  - Giant retroperitoneal liposarcoma. Report of 5 cases.
AB  - BACKGROUND: Liposarcoma is the most frequent histopathological variety of the
      retroperitoneum, surgery is the gold standard for treatment. CLINICAL SERIES: We
      report, retrospectively over 7 years (2000-2006), 5 cases (four men and one
      woman, the mean age was 48 years) of giant retroperitoneal liposarcomas and study
      their clinical characteristics intra operatively findings and course evolution.
      None of our patients had a percutaneous biopsy of his tumour. Surgery was
      indicated to all patients. Resection was performed in 4 cases (we performed a
      bloc resection in three cases and a simple tumour resection in one case), and in
      one case, abstention was decided. None of patients had an adjuvant therapy Three
      of the patients still alive after the follow up of 2, 3 and 4 years. CONCLUSION:
      Retroperitoneal liposarcomas represent a unique situation and require a more
      aggressive surgical approach including multiple resections for recurrences. Based
      on the ability of the patient to tolerate the procedure, surgery is suggested to
      evaluate resectability of the tumor. We must take into consideration whether
      prolonged survival will be attained and tumor removal will result in palliation
      of symptoms.

PMID- 22462340
TI  - The use of biological mesh to repair one large, contaminated abdominal wall
      defect due to neoplastic invasion. Report of a case.
AB  - We hereby report a case of use of biological mesh to repair one large,
      contaminated abdominal wall defect due to a sigmoid tumour presented as an
      abscess infiltrating the abdominal wall. Our patient was a 48-year-old woman. Her
      medical history was negative for any previous disease or surgical procedure.
      Because of the abscence of neoplastic secondarism an en-bloc resection of the
      interested sigmoid colon and of the infiltrated abdominal wall was performed,
      thus resulting a large wall defect in the left inguinal region. In order to close
      the wall defect a biological porcine collagen mesh was used. In our case we used
      a Permacol mesh made of porcine acellular dermal collagen. Reconstruction of
      complicated abdominal wall defects is a challenging surgical problem and primary
      repair is often difficult to achieve without excessive tension in the abdominal
      wall. The use of a syntethic mesh in this patient could have been inappropriate
      due to the possibility of creating adhesions with intra-abdominal viscera and
      fistula formation. We chose to use a biological mesh because of its safer
      properties in case of infected, inflamed or infiltrated surgical fields, as
      demonstrated in the literature.

PMID- 22462341
TI  - Complications after angiogram-negative subarachnoid haemorrhage: comparative
      study of pretruncal and nonpretruncal hemorrhage patients.
AB  - INTRODUCTION: Subarachnoid haemorrhages (SAH) of unknown aetiology usually have a
      mild clinical presentation, favourable outcome and low complication rate.
      OBJECTIVE: The aim of this study was to analyse the complications in two forms of
      angiogram-negative spontaneous SAH: pretruncal (PNSAH) and nonpretruncal
      (NPNSAH). METHODS: The study group involved 18 patients with PNSAH and 16
      patients with NPNSAH. CT scan was done within 72 hours from bleeding. All
      patients underwent four-vessel cerebral angiography. Repeat angiography was
      performed in five PNSAH and all NPNSAH patients. RESULTS: Twenty-nine patients
      were in grade I or II of the Hunt-Hess Scale (17 PNSAH and 12 NPNSAH). There was
      one case of rebleeding (NPNSAH patient), 10 cases of transient acute
      hydrocephalus (4 PNSAH and 6 NPNSAH). Cerebral vasospasm visualized by
      angiographies in two NPNSAH patients was local and mild, but was not found in
      PNSAH patients. Acute electrocardiography changes were found in 19 patients
      (significantly more frequently in NPNSAH than in PNSAH, 12 and 7 patients,
      respectively; p = 0.037). CONCLUSION: Cardiac problems following these types of
      SAH are more frequent than expected, and therefore cardiac monitoring is
      necessary.

PMID- 22462342
TI  - [Effects of diazepam and levodopa single doses on motor cortex plasticity
      modulation in healthy human subjects: a TMS study].
AB  - INTRODUCTION: Administration of pharmacological agents with specific actions on
      neurotransmitter systems is a powerful driver of functional cortical
      reorganization. Plastic reorganization of the motor cortex in humans studies by
      the use of non-invasive stimulation protocols, which mimic the Hebbian model of
      associative plasticity. OBJECTIVE: Aiming to explore pharmacological modulation
      on human motor cortex plasticity, we tested healthy subjects after each dosage of
      diazepam, levodopa i placebo administration, using paired associative stimulation
      protocol (PAS) that induce fenomena similar to a long-term potentiation and
      depression, as defined on the synaptic level. METHODS: We analyzed effects of
      benzodiazepines (10 mg), levodopa (200 mg) and placebo on PAS protocol in 14
      healthy volunteers, using a double-blind placebo-controlled study design. PAS
      consisted of electrical stimuli pairs at n.medianus and magnetic pulses over the
      scalp (transcranial magnetic stimulation) in precisely defined intervals (ISI was
      10 and 25 ms) for a total of about 15 minutes (200 pairs). MEP amplitudes before
      and after (0, 10, 20 and 30 minutes later) interventional protocols were
      compared. RESULTS: When protocols were applied with placebo depending on ISI (10
      ms--inhibitory, 25 ms--facilitatory effects), MEP amplitudes decreased or
      increased, while values in the post-interventional period (0, 10, 20 and 30 min)
      were compared with initial values before the use of SAS. The use of
      benzodiazepines caused the occlusion of LTP-like effect, in contrast to
      amplification effects recorded after the administration of levodopa. With respect
      to the LTD-like protocol, the reverse was true (ANOVA for repeat measurements p <
      0.001). CONCLUSION: Administration of GABA-ergic agonist diazepam interferes with
      the induction of associative plasticity in the motor cortex of healthy
      individuals, as opposed to the use of levodopa, which stimulates these processes.
      The observed effects point at a potential role of pharmacological modulation of
      plasticity in humans.

PMID- 22462343
TI  - Scanning electron microscopic examination of Enamel surface after fixed
      orthodontic treatment: in-vivo study.
AB  - INTRODUCTION: Therapy with fixed orthodontic appliances starts with bracket
      bonding and ends with debonding of brackets, leaving enamel surface varied.
      Objective The aim of this pilot study was to examine enamel surface before and
      after debonding of orthodontic brackets by the use of scanning electron
      microscopy (SEM). METHODS: Epoxy replicas of four patients' premolars indicated
      for therapy with fixed orthodontic appliances were made and brackets were bonded
      to their teeth with a different adhesives (Enlight, No-mix, Fuji Ortho LC and
      Heliosit Orthodontic) (n=4).Two months later, brackets on premolars were debonded
      and amounts of adhesive left on the tooth surfaces and the bracket bases were
      evaluated with the adhesive remnant index (ARI). After resin removal, epoxy
      replicas were made and the surface of premolars was evaluated with the enamel
      surface index (ESI). All replicas of premolars (n=32) were prepared for SEM
      examination and compared under different magnifications. Tooth damage was
      estimated based on correlation between ARItooth and ESI. RESULTS: Pearson's chi2
      test showed no significant differences between ARItooth and ARIbracket of four
      materials used. Nonparametric correlations showed significant differences between
      ARItooth and ARIbracket, ESI and ARItooth, and between ESI and ARIbracket.
      Increasing of ARItooth is followed with the descent of ARIbracket and the ascent
      of ESI. Multivariate regression analysis showed a significant correlation between
      ESI and ARItooth. CONCLUSION: Most bond failures took place at enamel-adhesive
      interface. ARItooth was a predictor to enamel surface damage. The type of
      material did not affect enamel surface damage.

PMID- 22462344
TI  - [The effect of antiaggregational therapy on the long-term patency of the
      femoropopliteal/crural bypass].
AB  - INTRODUCTION: Antiaggregational therapy can reduce thrombosis development
      following the arterial reconstruction surgery. In most cases acetylsalicylic acid
      and ticlopidine are used as antiaggregational agents. OBJECTIVE: The aim of this
      research was to examine the influence of different antiaggregational agents on a
      long-term femoropopliteal/crural bypass patency. METHODS: The study involved 142
      patients who underwent femoropopliteal/crural bypass reconstructions at the
      Cardiovascular Disease Institute of the Clinical Centre of Serbia. Most patient
      were operated on in the period from December 2007 to December 2009; however, the
      study also included a certain number of patients who had undergone surgery 1-7
      years earlier, and who were postsurgically under a regular check-up and
      examination. Depending on the administered antiaggregational agents, three groups
      of the patients were formed: (1) patients on 100 mg/daily acetylsalicylic acid;
      (2) patients on 2 x 250 mg/daily ticlopidine; and (3) patients on 100 mg/daily
      acetylsalicylic acid combined with 2x250 mg/daily ticlopidine. RESULTS: Among the
      formed groups in our study, there was no statistically significant difference in
      the femoropopliteal/crural bypass long-term patency, and the obtained patency
      values for each group were in accordance to the data from the literature.
      CONCLUSION: The first-choice antiaggregative agent after surgical infrainguinal
      arterial reconstruction procedures was found to be acetylsalicylic acid as
      compared to ticlopidin for at least two reasons: low cost and absence of
      neuthropenia as a side-effect.

PMID- 22462345
TI  - The role of oxidative stress in perinatal hypoxic-ischemic brain injury.
AB  - INTRODUCTION: The pathogenesis of perinatal hypoxic-ischemic brain damage is
      highly complex. OBJECTIVE: The aim of this study was to assess the role of
      oxidative stress in hypoxic-ischemic brain injury and subsequent abnormal
      neurological outcome in infants with perinatal hypoxic-ischemic encephalopathy
      (HIE). We estimated perinatal oxidative brain damage measuring activity of
      glutathione peroxidase (GPX) in cerebrospinal fluid (CSF) as an indirect
      biomarker of free radical production during cerebral hypoxia-ischemia in
      correlation with the level of intracellular enzyme neuron specific enolase (NSE)
      in CSF as a biomarker of extend of brain injury. METHODS: Ninety neonates (>32
      GA) with perinatal HIE were enrolled prospectively. HIE was categorized into
      three stages according Sarnat and Sarnat clinical scoring system and changes seen
      on amplitude integrated EEG. CSF for GPX analysis and NSE analysis was taken in
      the first 72 hours of life. Neurodevelopment outcome was assessed at 12 months of
      corrected gestational age. RESULTS: GPX activity in CSF was in good relation with
      clinical stage of HIE (p < 0.0001) and GA (p < 0.0001) and significantly
      corresponded with subsequent neurodevelopment outcome (p < 0.001). GPX activity
      in CSF showed a strong correlation with NSE levels in CSF (p < 0.001) as the
      biomarker of extent of brain injury. CONCLUSION: Our results suggest that
      oxidative stress might be important contributing factor in perinatal hypoxic
      ischemic brain damage, particularly in preterm neonates.

PMID- 22462346
TI  - Variations of serum copper values in pregnancy.
AB  - INTRODUCTION: Copper is essential micronutrient and has an important role in the
      human body. The serum copper increases during pregnancy and is doubled at full
      term. Lower levels of serum copper in pregnancy are connected with some
      pathological conditions. OBJECTIVE: The aim of this study was to estimate the
      levels of serum copper in normal and pathological pregnancies, comparing them
      with values of serum copper in non-pregnant women, to determine if serum copper
      is lower in some pathological pregnancies and if this is of some importance.
      METHODS: A total of 2170 plasma samples for copper analyses were made in the
      following groups: healthy non-pregnant women; healthy pregnant women from the 5th
      40th gestational week, during the first delivery stage and during the first three
      postpartum weeks, in pregnant women with habitual abortion, imminent abortion,
      abortion in progress, missed abortion (9th-24th weeks), missed labour and
      premature rupture of membranes (29th-40th weeks). Levels of serum copper were
      determined by colorimetric technique of bathocuproin with disulphate as a
      chromogen. RESULTS: Serum copper values in non-pregnant women range from 11.6
      25.8 micromol/L. In healthy pregnant women, there is a constant trend of the
      increase of serum copper. The mean serum copper values revealed three significant
      peaks at the 22nd, 27th and 35th gestational week. Serum copper values in the
      patients with some pathological pregnancies in relation to the serum copper
      values of the healthy pregnant women were significantly lower. CONCLUSION: Serum
      copper values can be used as an indicator of some pathological pregnancies.

PMID- 22462347
TI  - [Transobturator tension-free "inside-to-out" suburethral sling procedure for the
      treatment of stress urinary incontinence].
AB  - INTRODUCTION: Stress urinary incontinence is an involuntary leakage of urine on a
      sudden increase of intra-abdominal pressure by physical activity, exercise,
      coughing, sneezing or laughing. OBJECTIVE: To assess symptoms, functional and
      anatomical status of voiding function, complications and short term success of a
      novel procedure, tension-free vaginal tape obturator technique (TVT-O) in the
      treatment of stress urinary incontinence. METHODS: A prospective study was
      performed on 40 female patients who underwent the TVT-O suburethral sling at the
      Urology Department of the Health Centre in Prokuplje and Urology Hospital in Nis
      between May 2009 and February 2010. The mean patients' age was 58 years (range 34
      84 years). Preoperative evaluation included a detailed history and gynaecologic
      examination including urodynamic testing and voiding studies. UDI-6 and UIQ-7
      score testing was performed before, and six months after surgery. All patients
      who demonstrated stress urinary incontinence with a Q-tip test-angle during
      maximal straining were included into the study. Postoperatively, outcomes
      evaluation included voiding function, anatomical parameters, complications, as
      well as subjective success rates. RESULTS: In 30 patients surgery was performed
      under spinal and in ten under general anaesthesia. The average intraoperative
      blood loss during theTVT-O was minimal (<50 ml). There were no vascular, bladder,
      bowel, and neurological injuries. Thirty-eight patients (95%) were discharged
      voiding satisfactorily. There was a statistically significant difference in
      symptoms between UDI-6 and UIQ-7 before and after surgery. CONCLUSION: Initial
      experience with TVT-O suburethral sling is promising. The TVT-O differs from
      retropubic procedures by resulting in lower postoperative morbidity,
      intraoperative and postoperative complications.

PMID- 22462348
TI  - [Influence of moderate physical activity on the levels of plasma lipoproteins in
      subjects with impaired glucose tolerance].
AB  - INTRODUCTION: Physical activity and healthy diet, as lifestyle factors, are
      essential components in the prevention of chronic non-communicable diseases.
      Impared glucose intolerance (IGT) is an independent cardiovascular risk factor.
      Dyslipidaemia is a cardiometabolic risk factor for the development of type 2
      diabetes mellitus. OBJECTIVE: The aim of the study was to investigate the
      influence of moderate physical activity of plasma lipoprotein indicators in high
      risk subjects for diabetes mellitus during one-year planned intervention.
      METHODS: We randomly assigned 60 overweight subjects with IGT aged 30-60 years.
      The subjects were divided into intervention group with 30 subjects, who were
      intensively and individually instructed on weight reduction, nutrition and
      increased physical activity, and control group with 30 subjects, who were
      counselled, as standard, on nutrition and increased exercise. Total cholesterol
      (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides (Tg)
      were measured at the beginning of the study, and at 2 months, 6 months, and at
      the end of the study (12 months). RESULTS: Compared to the beginning of the
      study, after 2 and 6 months there was no statistically significant difference in
      serum lipid values. After 12 months, the average values of the measured lipid
      levels in the intervention group decreased by 18.36% for TC, 27.3% for LDL-C, and
      34.2% for Tg (compared to 10.27%, 13.45%, and 10.4%, respectively in the control
      group). Value of HDL-C in the intervention group increased by 19.12%, and
      decreased in the control group by 1.48%. Total/HDL-C ratio was reduced by 30.6%
      and LDL-C/H by 38.1% in the intervention group (compared to 12.36%, and 15.9% in
      the control group). After 12 months, significantly greater decrease in TC (p <
      0.01), LDL-C (p < 0.01) and Tg (p < 0.0001) and significantly greater increase in
      HDL-C (p < 0.05) was detected in the intervention group compared to the control
      group. CONCLUSION: Plasma lipoproteins can be significantly decreased by changes
      in the lifestyles of high-risk subjects during one-year planned intervention.

PMID- 22462349
TI  - Walking at speeds close to the preferred transition speed as an approach to
      obesity treatment.
AB  - INTRODUCTION: Increasing energy expenditure through certain exercise is an
      important component of effective interventions to enhance initial weight loss and
      prevent weight regain. OBJECTIVE: The purpose of this study was to determine the
      effect of a 16-week weight loss exercise programme on morpho-functional changes
      in female adults and to examine the programme effects on two subpopulations with
      different levels of obesity. METHODS: Fifty-six middle-aged women were divided
      into 2 groups according to their body mass index (BMI): 25-29.9 kg/m2--overweight
      (OW) and > or =30 kg/m2--obese (OB). The exercise protocol included a walking
      technique based on hip rotation at horizontal plane at speeds close to the
      preferred transition speed (PTS). At the initiation of the study and after 16
      weeks of the programme, anthropometric, morphological and cardiovascular
      parameters of all subjects were assessed. The main effects of Group (OW and OB)
      and Time and the interaction effect of Group by Time were tested by time repeated
      measures general linear model (mixed between-within subjects ANOVA). RESULTS:
      Mean weight loss during the programme was 10.3 kg and 20.1 kg in OW and OB,
      respectively. The average fat mass (FM) loss was 9.4 kg in OW and 16.9 kg in OB.
      The mixed ANOVA revealed a significant group by time interaction effects for
      waist circumference, body weight, body water, fat free mass, FM, %FM and BMI (p <
      0.05). CONCLUSION: The applied exercise protocol has proved as beneficial in the
      treatment of obesity, since it resulted in a significant weight loss and body
      composition changes. The reduction in body weight was achieved mainly on account
      of the loss of fat mass.

PMID- 22462350
TI  - [Infected tibial nonunions--treatment by the Ilizarov method: multicentric
      study].
AB  - INTRODUCTION: Associated bone tissue defect and infection, commonly result in non
      healing, i.e., by the development of infected tibial nonunion. OBJECTIVE: The aim
      of the paper was to present experiences acquired in the treatment of this problem
      by the application of the Ilizarov method. METHODS: The analyses enrolled 16
      patients diagnosed with infected tibial nonunion.The Ilizarov method was used in
      all the patients, of type bilocal synchronous compressive-distractive or bilocal
      alternating compressive-distractive. Bone and functional results were classified
      as excellent, good, fair and poor. Total follow-up period of the patients was
      48.77 +/- 41.57 months on the average. RESULTS: Fifteen (93.75%) cases of
      nonunions were successfully healed. According to the laboratory findings of
      inflammation, the same patients were also successfully treated for local
      infection. The inequality of the lower limbs was also resolved by new bone
      formation of average length of 5.75 +/- 3.29 cm. Poor result was verified in one
      (6.25%) patient only. The patient satisfaction was scored 3.73 +/- 1.33 and
      physician's satisfaction 4.33 +/- 1.11. CONCLUSION: The Ilizarov method with bone
      transport, because of being capable to solve simultaneously a local infection and
      tibial malalignement, and by substituting bone and soft tissue defects, thus
      enabling healing of until then unhealed bone, has shown as the best method in the
      treatment of this complex problem, infected tibial nonunions.

PMID- 22462351
TI  - [Dysfunctionality of the primary family as a supportive factor for the
      development of polytoxicomany in young people].
AB  - INTRODUCTION: Dependent behaviour represents a strong homeostasis of the family
      of an addict. OBJECTIVE: The aim of our research is to record and explore
      irregularities during the addicts' growth, as well as the specific type of family
      relations in the addicts' family. METHODS: For research purposes a general
      questionnaire was used on growth and development, and GRADIR questionnaire on the
      assessment of family relationships. RESULTS: Our results indicate that delinquent
      behaviour is often found with the addicts before the occurrence of abuse. A
      significant dysfunctional family of addicts was detected. Families with an addict
      were not substantially damaged or altered in terms of emotional exchange, but in
      their structure that enhanced dysfunction leading to addictive behaviour.
      CONCLUSION: Emotional investments without control, prohibitions and penalties,
      contribute to a lack of consciousness that disturbs the process of socialization.
      Due to the apparent control and the apparent support, the addicts do not have
      structured organization and socialization. Emotional stimuli without obligation
      for polytoxicomanes to maintain a reciprocal relationship with their parents
      influence the parental support of egoistic style of behaviour.

PMID- 22462352
TI  - [The association of demographic and socioeconomic determinants and self-perceived
      health].
AB  - INTRODUCTION: Inequalities in health are evident in the whole world and present
      an important and consistent public health issue. The highest contribution to the
      inequality in heath is attributable to the demographic and socioeconomic
      determinants of health. OBJECTIVE: The aim of this study was to analyse the
      association between the demographic (gender, age, marital status and type of
      settlement) and socioeconomic determinants of health (education and Wealth
      Index), and self-perceived health. METHODS: In the study the data from 2006
      National Health Survey of the population of Serbia were used. The interview
      involved 14,522 adults aged >20 years. The association between the demographic
      and socioeconomic determinants of health as independent variables, and self
      perceived health as dependent variable were examined using bivariate and
      multivariate logistic regression analyses. The minimum level of significance was
      p < 0.05. RESULTS: According to our study, the elderly and females significantly
      more often perceived their health as poor. Respondents living in rural settings
      were less likely to perceive their health as poor compared to those living in
      urban settings (odds ratio was 0.82 in males and 0.75 in females). Males with low
      education were three times more likely to perceive their health as poor (odds
      ratio was 3.46) in relation to males with high education. This association was
      more pronounced in females (odds ratio was 5.37). The same pattern was observed
      for Wealth Index. CONCLUSION: This study showed that demographic and
      socioeconomic inequalities in self-perceived health are present in Serbia.
      Comprehensive public health policies and interventions for reducing these
      inequalities are urgently needed with the primarily focus on the most
      disadvantaged socioeconomic groups.

PMID- 22462353
TI  - [Brugada syndrome: case report].
AB  - INTRODUCTION: Brugada syndrome is an arrhythmogenic disease characterized by
      coved ST segment elevation and J point elevation of at least 2 mm in at least two
      of the right precordial ECG leads (V1-3) and ventricular arrhythmias, syncope,
      and sudden death. Risk stratifications of patients with Brugada electrocardiogram
      are being strongly debated. CASE OUTLINE: A 23-year-old man was admitted to the
      Coronary Care Unit of the Clinical Centre "Bezanijska kosa" due to weakness,
      fatigue and chest discomfort. The patient suffered from fainting and
      palpitations. There was a family history of paternal sudden death at 36 years.
      Electrocardiogram showed a coved ST segment elevation of 4 mm in leads V1 and V2,
      recognised as spontaneous type 1 Brugada pattern. Laboratory investigations
      revealed normal serum cardiac troponin T and serum potassium, and absence of
      inflammation signs. Echocardiographic finding was normal, except for a mild
      enlargement of the right atrium and ventricle. The diagnosis of Brugada syndrome
      was made by Brugada-type 1 electrocardiogram and the family history of sudden
      death <45 years. The patient was considered as a high risk, because of pre
      syncope and palpitations. He underwent ICD implantation (Medtronic
      MaximoVR7232Cx) using the standard procedure. After implantation, noninvasive
      electrophysiology study was done and demonstrated inducible VF that was
      interrupted with the second 35 JDC shock. The patient was discharged in stable
      condition with beta-blocker therapy. After a year of pacemaker check-ups, there
      were no either VT/ VF events or ICD therapy. CONCLUSION: Clinical presentation is
      the most important parameter in risk stratification of patients with Brugada
      electrocardiogram and Brugada syndrome.

PMID- 22462354
TI  - [Non-inflammatory aortoiliac aneurysm with ureteral obstruction and consequent
      hydronephrosis: case report].
AB  - INTRODUCTION: The natural course of abdominal aneurysms is progressive expansion,
      rupture, embolisation, thrombosis and compression of the visceral organs. The
      majority of papers report that inflammatory aortic and iliac aneurysms are
      associated with perianeurysmal and retroperitoneal fibrosis that ultimately
      results in the structural compromise of the urinary tract. Ureteral obstruction
      occurs in 20% to 71% of cases and approximately one half of these patients will
      present with obstructive uropathy. Most patients with inflammatory aneurysm are
      symptomatic, with elevated serum inflammatory markers, and characteristic
      multislice CT findings including a thickened aortic wall and a mass of periaortic
      inflammatory tissue. CASE OUTLINE: A 70-year-old man was admitted at the Vascular
      Surgery Clinic "Dedinje", Belgrade, because of ultrasonically verified
      asymptomatic aortoiliac aneurysm. Multisclice CT findings showed left urethral
      dilatation and hydronephrosis secondary to extrinsic ureteral obstruction due to
      aortoiliac aneurysm. CT findings, laboratory tests and finally, histopathologic
      examination showed atherosclerotic aneurysm without inflammation and
      retroperitoneal fibrosis. The patient was successfully treated with surgical
      resection of the aneurysm and aortobiliac reconstruction with "Y" prosthesis.
      CONCLUSION: We present a rare case of ureteral obstruction secondary to
      atherosclerotic aneurysm which, to our knowledge, has not been previously
      described in the domestic literature. A successful operative repair was
      performed. Postoperative course was uneventful and the patient was discharged on
      the seventh day after the surgery with normal vascular status and renal function.

PMID- 22462355
TI  - [Intraabdominal abscesses of unknown etiology].
AB  - INTRODUCTION: Intraabdominal abscesses are in 98-99% cases the result of
      secondary and only in 1-2% of primary peritonitis. They are easy and successfully
      diagnosed. Abdominal abscesses of unknown cause are extremely rare. CASE OUTLINE:
      The authors present a 68-year-old man, without significant data in past history,
      who suddenly developed epigastric pain, nausea, vomiting and leukocytosis which
      was treated with antibiotics resulting in the alleviation of complaints and
      reduction of white blood cells count. After five days ultrasonography showed
      incapsulated collection of dense fluid in the epigastrium confirmed by CT scan
      two days later. Upper endoscopy excluded ulcer and/or perforation of the stomach
      and duodenum. Under local anesthesia, through the upper part of the left rectal
      muscle, puncture followed by incision was done, and about 50 ml of dense pus was
      removed. Finger exploration of the cavity showed no foreign body within the
      cavity. Using drainage, the recovery was quick and uneventful. By preoperative
      and postoperative abdominal investigations no cause of the abscess was found. Two
      and a half years after surgery the patient remained symptom-free with normal
      clinical, laboratory and ultrasonographic findings. CONCLUSION: The authors
      presented an intraabdominal abscess of unknown cause that was successfully
      treated with antibiotics, percutaneous puncture and drainage under local
      anaesthesia. In spite of all diagnostic methods the cause of the abscess could
      not be found. Thus, such a possibility, although being rare, should be taken into
      account.

PMID- 22462356
TI  - [Ultrasonography and magnetic resonance imaging in prenatal diagnosis of tumour
      of the foetal head and neck].
AB  - INTRODUCTION: Foetal tumours are relatively rare; prenatal diagnosis enables
      additional diagnostics, and thus the decision on the continuation of pregnancy
      and planning of delivery. The paper presents prenatal ultrasound diagnostics of
      foetal head tumour with additionally analyzed magnetic resonance imaging (MRI).
      CASE OUTLINE: On ultrasound imaging, in a 27-year-old nullipara, a tumour of the
      foetal head was suspected at the 22nd gestational week. By consultative
      ultrasound, a 45 x 41 x 50 mm echogenic soft tissue tumour with hypoechogenic
      areas was confirmed, which originated from the left side of the skull spreading
      towards the neck on the left behind the ear. On colour Doppler no vascularisation
      was seen within the tumour but several vessels were seen along the border-line
      and on the surface. The scan showed no associated abnormalities. Karyotype was
      46, XY. MRI scan using triplanar SSFSE and HASTE sequences was done at 26 weeks
      and confirmed a 84 x 45 x 71 mm tumour originating from the scalp, spreading
      along the endocranium over the entire surface of the fronto-temporal sqama and
      left parietal bone. The tumour did not disturb the integrity of the internal
      tabula, and did not spread intracranially. Based on these findings, the diagnosis
      of haemangioma was made. At 38 weeks gestation, a 3810 g male infant was
      delivered by Caesarean section. A bluish, well-defined, non-pulsatile tumour
      arising from the left frontoparietal region was seen, thus confirming the
      diagnosis of haemangioma. CONCLUSION: MRI improved delineation of the tumour
      facilitating better planning of postnatal management and mode of delivery, with
      the information on the postnatal course and prognosis. In the prenatal period,
      MRI following an ultrasound diagnosed foetal tumour, is an additional part of
      diagnostic examinations, and is not contraindicated during pregnancy.

PMID- 22462357
TI  - [Systemic mastocytosis: case report with literature review].
AB  - INTRODUCTION: Mastocytosis is a clonal neoplastic disorder of the mast cells. The
      clinical signs and symptoms of mastocytosis are heterogeneous ranging from
      indolent disease with a long-term survival to a highly aggressive neoplasm with
      survival of about 6 months. Systemic mastocytosis (SM) is characterized by
      mastocyte infiltration of one or more organs, with or without skin involvment.
      CASE OUTLINE: The presented patient presents a highly challenging diagnostic and
      therapeutic case. A 46-year-old man was referred to our Centre due to the 7-year
      long history of hepatosplenomegaly and mild thrombocytopenia. Ultrasound
      examination showed hepatosplenomegaly (liver 170 mm; spleen 200 mm), platelet
      count was 90 x 10(9)/L, serum tryptase level was elevated and bone marrow biopsy
      showed infiltration with mast cells (CD117, CD25 and mast cell tryptase
      positive). Our patient was diagnosed with aggressive systemic mastocytosis (SM)
      according to WHO Classification (2008), although the clinical course of the
      disease was indolent, without complications for more than 7 years. Because of the
      'intermediate' course, this patient was referred to as smouldering or
      intermediate SM and was not treated with cytostatics. CONCLUSION: Utilizing the
      established criteria, indolent SM can be discriminated from the aggressive
      subvariants of SM in most cases. However, a small group of patients, like our
      case belongs to the "grey zone". Therapeutic approach to these patients is
      individual and prognosis is uncertain.

PMID- 22462358
TI  - Fatigue in sarcoidosis: detection and treatment.
AB  - Fatigue is a prominent symptom in a large number of medical conditions, malignant
      and infectious diseases. Fatigue is also a prominent symptom of sarcoidosis. The
      occurrence of fatigue in sarcoidosis is well known but exact incidence has not
      been established and varies from 30-70% of patients depending on age, sex and
      organ involvement by the granulomatous process. The exact definition of fatigue
      varies broadly. It can be both physical and mental. The patients describe their
      sensation of fatigue qualitatively different from that fatigue they experienced
      before they became sick. Fatigue has a major impact on the quality of life in
      sarcoidosis. Establishing the extent of fatigue in sarcoidosis provides relevant
      insight regarding the patient's quality of life. Unfortunately there is no
      objective parameter for assessing fatigue in sarcoidosis. Generally, fatigue is
      detected by means of questionnaires. Regarding the therapy, there is no effective
      treatment for fatigue in sarcoidosis.

PMID- 22462359
TI  - Vitamin D in the light of current knowledge.
AB  - Vitamin D, i.e., 1.25(OH)2D, is an essential factor, not only of homeostasis of
      calcium and phosphorus, but also of cell proliferation, differentiation and
      apoptosis, immune and hormonal regulation, as well as other body processes.Thus,
      its optimal presence in the body is of exceptional significance for health, both
      of children, as well as adults and elderly persons. Today, it is known that the
      lack of vitamin D, besides having negative effects on the skeleton and teeth,
      also contributes to the development of various malignancies, primarily of the
      large bowel, prostate and breasts, as well as of autoimmune and allergic
      diseases, diabetes mellitus type II, arterial hypertension and others. Considered
      from the biological aspect, physiological requirements in vitamin D are achieved
      by cutaneous synthesis from 7-dehydrocholesterol during sun exposure, while,
      except rarely, it is very scarce in food. Having in mind extensive evidence that
      sun exposure presents a high risk for the development of skin malignancies,
      primarily melanoma, it is clear that humans are deprived of the natural and basic
      source of vitamin D. In accordance, as well as based on numerous epidemiological
      studies showing the increase of diseases, in the basis of which vitamin D
      deficiency plays the important role, next led to the recommended dietary
      allowance of vitamin D, regardless of age. According to current attitudes, it is
      recommended that the daily dietary allowances of vitamin D, i.e., the quantity of
      oral intake that would safely cover the optimal body requirements should be 400
      IU for ages 0-18 years, 600 IU for ages 19-70 years and 800 IU for persons aged
      over 70 years.

PMID- 22462360
TI  - [Maria Muller (1883-?) M.D., ophthalmologist: biographical notes].
AB  - Maria Muller was one of the first female ophthalmologists in Serbia. Having
      researched the documents from several archives in Serbia-Belgrade, Novi Sad and
      Sremska Mitrovica, we were able to follow her life and work. Maria Muller was
      born in Budapest in 1883. From 1909 to 1919 she worked at the Budapest Hungarian
      Royal State Eye Hospital headed by the famous ophthalmologist professor Ladislav
      Blaskovic. She arrived in Belgrade in 1920, and from March 1921 to November 1941
      she worked as an ophthalmologist in Sabac. She founded and headed the Eye
      Department as well as the Trachoma Outpatients' Department, giving great
      contribution to the development of ophthalmology in Sabac and the neighbouring
      region. From 1941 to 1946 Maria Muller worked in Petrovgrad (Veliki Beckerek),
      today's Zrenjanin, as the chief of Trachoma Department, while from 1946 in
      Sremska Mitrovica as the head of the Eye Department. The contribution of Dr.
      Maria Muller to the development of ophthalmology, especially in trachoma case
      detection and treatment, is without any doubt outstanding.

PMID- 22462361
TI  - Plagiarism--how to deal with it?

PMID- 22462363
TI  - Looking to make employees healthier and more productive? Here are five ideas
      companies are already using.

PMID- 22462362
TI  - Building trust inside your company. Interview by Colleen Leahey.

PMID- 22462364
TI  - Making health fun.

PMID- 22462365
TI  - Space shuttle flight crew spatial orientation survey results.
AB  - BACKGROUND & METHOD: A survey was distributed to 77 Space Shuttle flight crew
      members; 40 responded covering 71 missions. The goal was to capture historical
      information before Shuttle retirement and to better understand subjective
      experiences of illusory sensations due to the transition from 1-G to microgravity
      and back. RESULTS: We analyzed the response data to answer four questions: 1) Do
      older astronauts suffer more from illusory sensations than younger astronauts? We
      conclude that they do not because younger flight crew had about twice the rate of
      illusory sensations as older flight crew. 2) Do trial head motions during re
      entry in an effort to hasten readaptation to 1-G really help? Apparently not
      because those who made trial head motions had a 38% rate of illusory sensations
      whereas those who did not make trial head motions had a 15% rate of illusory
      sensations. 3) Do symptoms decrease as flight experience increases? Yes, as
      reported in other publications, although there are individual exceptions. 4) Do
      longer duration missions lead to more illusory sensations and readaptation
      difficulties than shorter duration missions? Yes, the rate of illusory sensations
      for longer missions was 38%, whereas it was 24% for shorter missions. DISCUSSION:
      Based upon our results, long-duration missions may induce orientation problems
      that could have significant mission impacts.

PMID- 22462366
TI  - Subfoveal choroidal thickness and foveal retinal thickness during head-down tilt.
AB  - INTRODUCTION: To reveal subtle morphological changes in the eye during simulated
      microgravity for spaceflights, we measured subfoveal choroidal thickness and
      foveal retinal thickness during 10 degrees head-down tilt (HDT). We hypothesized
      that elevated ophthalmic vein pressure during simulated microgravity increases
      subfoveal choroidal thickness via enlargement of the choroidal vasculature and
      greater choroidal blood volume. METHODS: The right eyes of nine healthy subjects
      (seven men, two women) were examined. Subfoveal choroidal thickness and foveal
      retinal thickness were measured using spectral domain-optical coherence
      tomography in the sitting position, and after 15 and 30 min of 10 degrees HDT.
      Intraocular pressure was also measured. RESULTS: Mean subfoveal choroidal
      thickness (+/- SEM) increased from 300 +/- 31 microm in the sitting position to
      315 +/- 31 microm with 15-min HDT, and 333 +/- 31 microm with 30-min HDT.
      However, no change in foveal retinal thickness was observed (228 +/- 9 microm in
      the sitting position, 228 +/- 10 microm with 15-min HDT and 228 +/- 9 microm with
      30-min HDT). Intraocular pressure increased from 14 +/- 1 mmHg in the sitting
      position to 21 +/- 2 mmHg with 30-min HDT (54 +/- 6%, N = 5). DISCUSSION:
      Subfoveal choroidal thickness and intraocular pressure were increased by HDT
      during simulated microgravity, although no change in foveal retinal thickness was
      observed.

PMID- 22462367
TI  - Temporal artery Doppler spectrum morphology responses to tilt and LBNP as an
      early indicator of syncope.
AB  - OBJECTIVE: In a study to identify an early hemodynamic predictor of syncope, 12
      men (25-40 yr) underwent 30 min of 80 degrees head-up tilt, followed by
      progressive lower body negative pressure (LBNP) until presyncope. METHODS:
      Temporal (supplying extracranial tissues: TEMP), middle cerebral (MCA), and
      superficial femoral (FEM) arterial flow velocity (V) and vascular resistance
      indices (VR) were evaluated continuously using Doppler ultrasound. Ratios of the
      Doppler V(MEAN) (V(MCA)/V(FEM) or V(MCA)/ V(TEMP)) were used to assess flow
      redistribution between these areas. RESULTS: The progression of the testing
      protocol showed increases in vascular resistance in all territories. At
      presyncope, both MCA(VR) and FEM(VR) were reduced while there was a large
      increase in TEMP(VR). Vasoconstriction of the vascular bed supplied by the
      temporal artery occurred early during central hypovolemia resulting in the
      appearance of negative velocity deflections, which could be used for the early
      detection of impending syncope. Analysis of the velocity ratios showed little
      change until the onset of presyncope where there was an increase in
      V(MCA)/V(TEMP) which confirmed that vasoconstriction of the vascular bed supplied
      by the TEMP artery contributed to cardiac output redistribution in favor of the
      brain, and a reduction in V(MCA)/V(FEM) suggesting a redistribution of cardiac
      output toward the legs. DISCUSSION: In 67% of the tests, the appearance of the
      negative component of V(TEMP) was an early sign of increasing TEMP(VR) that
      occurred before visually detectable changes in VE(FEM) or V(MCA) and within 5 min
      before presyncope. Such easily identifiable in real time Doppler signs allowed
      experimenters to anticipate test termination.

PMID- 22462368
TI  - Orthostatic hypotension after 10 days of exercise-heat acclimation and 28 hours
      of sleep loss.
AB  - INTRODUCTION: Orthostatic hypotension (OH) occurs among several populations;
      elevated temperatures increase an individual's susceptibility, whereas the effect
      of sleep loss (SL) remains inconclusive. The purpose was: 1) to evaluate the
      effects of 10 d of heat acclimation (HA) and 28 h of SL on OH; and 2) to
      determine the best measurements to assess OH in clinical and field settings.
      METHODS: There were 11 men (mean +/- SD; age, 20 +/- 1 yr; mass, 81.7 +/- 12.2
      kg) who underwent a repeated measures research design. Before and after 90 min of
      HA, with the 11th day performed in conjunction with SL, subjects performed a lie
      to-stand test where blood pressure (BP), heart rate (HR), and OH signs and
      symptoms were obtained. RESULTS: OH incidence and intensity, assessed via acute
      changes in post-exercise systolic BP (SBP), significantly decreased during HA
      from Day 2 (15 +/- 12 mmHg) to Day 8 (8 +/- 8 mmHg), while SL showed no effect.
      As OH responses decreased, concomitant HR increases diminished from Day 2 (113 +/
      15 bpm) to Day 8 (103 +/- 14 bpm). Post-exercise lightheadedness, dizziness, and
      nausea significantly decreased from Day 2 to Day 8, while no changes were
      associated with SL. CONCLUSIONS: During HA, BP control improved and
      cardiovascular strain was reduced, along with OH signs and symptoms; mild SL had
      no measurable effect. Acute HR changes may be explained by decreased cardiac
      output and increased stroke volume. In clinical settings, SBP delta may indicate
      the threshold at which OH signs and symptoms arise. In the absence of a
      sphygmomanometer, HR taken upon standing, or ratings of lightheadedness and
      dizziness may be used as alternative field expedient techniques.

PMID- 22462369
TI  - Victim fragmentation patterns and seat location supplements crash data: American
      Airlines flight 587.
AB  - INTRODUCTION: In 2001, American Airlines flight 587 crashed shortly after
      takeoff. All 260 people aboard and 5 people on the ground were killed. This
      study's objective was to explore the extent of victim injuries and fragmentation
      patterns along with their assumed seat locations as related to the crash event
      and the plane's structural damage. METHODS: There were 2058 body fragments
      recovered and, of those, 1750 have been identified. Autopsy reports detailing
      injuries and extent of fragmentation, flight manifest, and the NTSB Aircraft
      Accident Report were examined for correlations among injuries, seat location, and
      crash event. Using the AIS as a model, a fragmentation scale was designed to
      record injury location and severity, with a focus on the extremities. RESULTS:
      More whole bodies were recovered from victims seated on the plane's right side
      and back half. Conversely, significantly more fragments for victims seated on the
      plane's left side were recovered. The increased fragmentation from victims on the
      left side is an irregular pattern, particularly because the last information from
      the flight data recorder showed the plane's sideslip to the right. However, there
      are no data for the flight's final 13.6 s. Most eyewitnesses recount the plane
      rolling left before crashing. The increased fragmentation of victims seated on
      the left is consistent with structural damage from a left side impact,
      corroborating eyewitness accounts. CONCLUSIONS: Correlating victim injuries and
      fragmentation patterns, seat location, and the plane's structural damage can
      assist an investigation into plane crashes, particularly if flight data are
      missing.

PMID- 22462370
TI  - Transient immune impairment after a simulated long-haul flight.
AB  - INTRODUCTION: Almost 2 billion people travel aboard commercial airlines every
      year, with about 20% developing symptoms of the common cold within 1 wk after air
      travel. We hypothesize that hypobaric hypoxic conditions associated with air
      travel may contribute to immune impairment. METHODS: We studied the effects of
      hypobaric hypoxic conditions during a simulated flight at 8000 ft (2438 m)
      cruising altitude on immune and stress markers in 52 healthy volunteers (mean age
      31) before and on days 1, 4, and 7 after the flight. We did a cohort study using
      a generalized estimating equation to examine the differences in the repeated
      measures. RESULTS: Our findings show that the hypobaric hypoxic conditions of a
      10-h overnight simulation flight are not associated with severe immune impairment
      or abnormal IgA or cortisol levels, but with transient impairment in some
      parameters: we observed a transient decrease in lymphocyte proliferative
      responses combined with an upregulation in CD69 and CD14 cells and a decrease in
      HLA-DR in the immediate days following the simulated flight that normalized by
      day 7 in most instances. DISCUSSION: These transient immune changes may
      contribute to an increased susceptibility to respiratory infections commonly seen
      after long-haul flights.

PMID- 22462371
TI  - Respiratory-related limitations in physically demanding occupations.
AB  - Respiratory muscle work limits high-intensity exercise tolerance in healthy human
      beings. Emerging evidence suggests similar limitations exist during submaximal
      work in some physically demanding occupations. In an occupational setting, heavy
      loads are routinely carried upon the trunk in the form of body armor, backpacks,
      and/or compressed air cylinders by military, emergency service, and mountain
      rescue personnel. This personal and respiratory protective equipment impairs
      respiratory muscle function and increases respiratory muscle work. More
      specifically, thoracic load carriage induces a restrictive ventilatory limitation
      which increases the elastic work of breathing, rendering the respiratory muscles
      vulnerable to fatigue and inducing a concomitant reduction in exercise tolerance.
      Similarly, breathing apparatus worn by occupational personnel, including fire
      fighters and military and commercial divers, increases the inspiratory elastic
      and expiratory resistive work of breathing, precipitating significant inspiratory
      and expiratory muscle fatigue and a reduction in exercise tolerance. An argument
      is presented that the unique respiratory challenges encountered in some
      occupational settings require further research, since these may affect the
      operational effectiveness and the health and safety of personnel working in
      physically demanding occupations.

PMID- 22462372
TI  - Arterial oxygen pressure following whole-body vibration at altitude.
AB  - INTRODUCTION: Most helicopter operations are carried out at altitudes below
      10,000 ft. At these altitudes, the risk of the crew experiencing hypoxia is low.
      For that reason, supplementary oxygen is not standard equipment on board most
      helicopters. Due to developments in military missions, high-altitude operations
      have become more frequent-as have the chances of the crew experiencing hypoxia.
      Helicopter crews are subjected to a higher load of whole-body vibration compared
      to fixed-wing aircraft crews. Whole-body vibration increases muscle work, with
      increased oxygen consumption as a result. We hypothesized that whole-body
      vibration, as experienced by helicopter crews, causes additional lowering of
      arterial oxygen levels under hypoxic conditions. METHODS: Data were collected
      from 10 subjects. They were all exposed to six different pressure altitudes in a
      hypobaric chamber, ranging from 1000 ft to 16,000 ft (approximately 305 m to
      approximately 4877 m). Arterial blood samples were drawn on two occasions at each
      altitude: after 14 min of rest and followed by 15 min of whole-body vibration (17
      Hz, at 1.1 m x s(-2) in the z-axis) at each altitude. RESULTS: There was no
      significant effect of whole-body vibration on arterial oxygen pressure at
      altitudes up to 16,000 ft (approximately 4877 m), nor was there any effect on
      ventilation, seen as changes in arterial pressure of CO2. DISCUSSION: We
      contribute the lack of effect to the low vibration intensity used in this study.
      Since this vibration intensity was higher than experienced by helicopter crews
      during flight, we conclude that whole-body vibration does not contribute to
      hypoxia during high-altitude operations in helicopters.

PMID- 22462373
TI  - Critical care aeromedical evacuation staff in Batang Airport after the Yushu
      earthquake at high altitude.
AB  - OBJECTIVE: Aeromedical evacuation (AE), which is not well-developed in many less
      developed countries, becomes increasingly important in preserving function and
      saving lives during disasters. Our primary goal was to describe and analyze the
      age, specialty, the relevant training or operational experience, attitude toward
      professional training, and main difficulties during aeromedical evacuation in
      critical care AE staff after the 2010 Yushu earthquake in China. METHODS: A total
      of 120 questionnaires were sent to AE staff and 114 responses were received.
      There were 77 members involved in AE who were classified into an AE Group, and
      the other 37 were classifed into an Airport Group. RESULTS: Those whose ages were
      between 26 and 35 yr old accounted for the largest proportion of both groups; the
      top 3 specialties of the 114 responders were surgery (28.95%), internal medicine
      (28.07%), and emergency medicine (16.67%). Few of the staff had participated in
      AE operations or training before they were sent to Batang Airport. However, the
      proportion of members with experience in other emergency medical operations or
      training programs in the AE Group was higher. Staff in both groups agreed that
      the critical care capacity of AE needed to be improved (N = 107, 93.86%) and the
      need for specialized training was high (N = 105, 92.11%). The main problems
      raised by the AE Group members were narrow cabin, airsickness, lack of medical
      equipment, poor coordination, noise, aircraft turbulence, and low air pressure.
      CONCLUSIONS: The results of the study supported the urgent requirement for
      building a professional critical care AE unit with well-equipped medical staff
      and facilities, and for founding a formal critical care training program in AE.

PMID- 22462374
TI  - Crew resource management: using aviation techniques to improve operating room
      safety.
AB  - INTRODUCTION: Since the publication of the Institute of Medicine report
      estimating nearly 100,000 deaths per year from medical errors, hospitals and
      physicians have a renewed focus upon error reduction. We implemented a surgical
      crew resource management (CRM) program for all operating room (OR) personnel.
      METHODS: In our academic medical center, 19,000 procedures per year are performed
      in 27 operating rooms. Mandatory CRM training was implemented for all peri
      operative personnel. Aviation techniques introduced included a pre-operative
      checklist and brief, post-operative debrief, read and initial files, and various
      other aviation-based techniques. Compliance with conduct of the brief/debrief was
      monitored as well as wrong-site surgeries and retained foreign body events. The
      malpractice insurance database for claims was also queried for the period prior
      to and after training. RESULTS: Initial training was accomplished for 517 people,
      including all anesthesiologists, surgeons, nurses, technicians, and OR
      assistants. Pre-operative briefing increased from 6.7 to 99% within 4 mo. Wrong
      site surgeries and retained foreign bodies decreased from a high of seven in 2007
      to none in 2008, but, after 14 mo without additional training, these rose to five
      in 2009. Malpractice expenses (payouts and legal fees) totaled $793,000 (2003
      2007), but have been zero since 2008. DISCUSSION: CRM training and implementation
      had an impact on reducing the incidence of wrong site surgery and retained
      foreign bodies in our operating rooms. However, constant reinforcement and
      refresher training is necessary for sustained results. Though no one technique
      can prevent all errors, CRM can effect culture change, producing a safer
      environment.

PMID- 22462376
TI  - Biological databases as research tools in the post-genomic era.

PMID- 22462375
TI  - Rethinking nephrolithiasis in military aviation.
AB  - BACKGROUND: Nephrolithiasis is a common medical condition among aviation
      personnel that can negatively impact their health and careers. Due to the
      potentially severe consequences of in-flight renal colic associated with
      nephrolithiasis, current Navy regulations stipulate extensive evaluation for any
      aircrew member who has an instance of kidney stones. CASE REPORT: Two cases of
      Naval aircrew members with kidney stones are reviewed and current Navy standards
      regarding nephrolithiasis are discussed. DISCUSSION: Current Navy standards for
      granting aeromedical waivers for kidney stones do not differentiate between
      pilots in actual control of the aircraft and other aircrew members among aircraft
      personnel. Furthermore, a premium is placed on stone-free status, even for
      asymptomatic, incidentally found nephroliths. This policy has many similarities,
      but also significant differences from those of other services and those of
      civilian aviation authorities. This difference in protocols across aviation
      communities should be re-examined in order to promote more efficient return to
      flying duties of operational personnel without compromising safety of flight.

PMID- 22462378
TI  - This month in aerospace medicine history.

PMID- 22462377
TI  - You're the flight surgeon: visceral leishmaniasis.

PMID- 22462379
TI  - How careproviders can acquire and apply greater wisdom.
AB  - In this issue of JCE, Baum-Baicker and Sisti present senior psychoanalysts' views
      of wisdom. Although views on wisdom differ widely, there is agreement that when
      ethical conflicts arise, wisdom may be critical in bringing about an optimal
      result. Here I will present recent empirical findings on wisdom and the ways
      careproviders may acquire and apply it, especially in ethical conflicts.The
      findings are not well-known and may seem counterintuitive; I selected them, in
      large part, for those reasons. A core challenge may be to decide when to give
      patients standard care and when to make exceptions. In this issue of JCE, Baum
      Baicker and Sisti discuss exceptions and Bursztajn and colleagues consider how
      these exceptions may be further validated as evidence-based treatments.

PMID- 22462380
TI  - Clinical wisdom in psychoanalysis and psychodynamic psychotherapy: a
      philosophical and qualitative analysis.
AB  - To precisely define wisdom has been an ongoing task of philosophers for
      millennia. Investigations into the psychological dimensions of wisdom have
      revealed several features that make exemplary persons "wise." Contemporary
      bioethicists took up this concept as they retrieved and adapted Aristotle's
      intellectual virtue of phronesis for applications in medical contexts. In this
      article, we build on scholarship in both psychology and medical ethics by
      providing an account of clinical wisdom qua phronesis in the context of the
      practice of psychoanalysis and psychodynamic psychotherapy. With the support of
      qualitative data, we argue that the concept of clinical wisdom in mental
      healthcare shares several of the key ethical dimensions offered by standard
      models of phronesis in medical ethics and serves as a useful, albeit overlooked,
      reference point for a broader development of virtue-based medical ethics. We
      propose that the features of clinical wisdom are pragmatic skills that include,
      but are not limited to, an awareness of balance, the acceptance of paradox, and a
      particular clinical manner that maintains a deep regard for the other. We offer
      several suggestions for refining training programs and redoubling efforts to
      provide long-term mentorship opportunities for trainees in clinical mental
      healthcare in order to cultivate clinical wisdom.

PMID- 22462381
TI  - Response: Clinical wisdom and evidence-based medicine are complementary.
AB  - A long-debated question in the philosophy of health, and contingent disciplines,
      is the extent to which wise clinical practice ("clinical wisdom") is, or could
      be, compatible with empirically validated medicine ("evidence-based medicine"-
      EBM). Here we respond to Baum-Baicker and Sisti, who not only suggest that these
      two types of knowledge are divided due to their differing sources, but also that
      EBM can sometimes even hurt wise clinical practice. We argue that the distinction
      between EBM and clinical wisdom is poorly defined, unsupported by the methodology
      employed, and ultimately incorrect; crucial differences exist, we argue, not in
      the source of a particular piece of clinical knowledge, but in its dependability.
      In light of this subtle but fundamental revision, we explain how clinical wisdom
      and EBM are--by necessity--complementary, rather than in conflict. We elaborate
      on how recognizing this relationship can have far-reaching implications for the
      domains of clinical practice, medical education, and health policy.

PMID- 22462382
TI  - Attending to clinical wisdom.
AB  - In response to the article by Baum-Baicker and Sisti, I will consider the kind of
      wisdom involved in therapeutic listening; the role of life wisdom; and the
      challenge of imparting clinical wisdom to young health professionals' education.

PMID- 22462383
TI  - Her own decision: impairment and authenticity in adolescence.
AB  - This case describes an adolescent in a crisis of a chronic medical condition
      whose situation is complicated by substance abuse and mental illness. D. Micah
      Hester provides an analytic approach, teasing apart the multiple layers of
      medical, developmental, and moral issues at hand and describing possible
      responses and outcomes. Amy T. Campbell examines existing legal guidelines for
      adolescent decision making, arguing that greater space exists for clinical
      discretion in these matters than commonly thought. Cheryl D. Lew discusses the
      development of agency in adolescent patients, the ideal of autonomous decision
      making in the context of impairment and chronic illness, and the obligation of
      healthcare teams to examine an adolescent patient's decisions in relation to her
      identity.

PMID- 22462384
TI  - Supporting her autonomy: the obligations of guardians and physicians in
      adolescents' refusals of care.
AB  - This commentary on "Her Own Decision: Impairment and Authenticity in Adolescence"
      by Campbell, Derrington, Hester, and Lew adds further consideration of
      obligations for guardians and physicians of minors who struggle in making serious
      decisions regarding medical treatment.

PMID- 22462385
TI  - Intraoperative conversion to open technique: is informed consent implied?
AB  - This case raises issues regarding the anesthesia and surgical components of
      preoperative informed consent and the differing views of anesthesiologists and
      surgeons with regards to informed consent, in the context of conversion to open
      surgery from a minimally invasive approach.

PMID- 22462386
TI  - Anesthesiological ethics: can informed consent be implied?
AB  - Surgical ethics is a well-recognized field in clinical ethics, distinct from
      medical ethics. It includes at least a dozen important issues common to surgery
      that do not exist in internal medicine simply because of the differences in their
      practices. But until now there has been a tendency to include ethical issues of
      anesthesiology as a part of surgical ethics. This may mask the importance of
      ethical issues in anesthesiology, and even help perpetuate an unfortunate view
      that surgeons are "captain of the ship" in the operating theater (leaving
      anesthesiologists in a subservient role). We will have a better ethical
      understanding if we see surgery and anesthesia as two equal partners, ethically
      as well as in terms of patient care. Informed consent is one such issue, but it
      is not limited to that. Even on the topic of what type of anesthesia to use,
      anesthesiologists have often felt subsumed to the surgeon's preferences. This
      commentary takes the case study and uses it as a exemplar for this very claim: it
      is time to give due recognition for a new field in clinical ethics, ethics in
      anesthesia.

PMID- 22462387
TI  - Surrogate medical decision making on behalf of a never-competent, profoundly
      intellectually disabled patient who is acutely ill.
AB  - With the improvements in medical care and resultant increase in life expectancy
      of the intellectually disabled, it will become more common for healthcare
      providers to be confronted by ethical dilemmas in the care of this patient
      population. Many of the dilemmas will focus on what is in the best interest of
      patients who have never been able to express their wishes with regard to medical
      and end-of-life care and who should be empowered to exercise surrogate medical
      decision-making authority on their behalf. A case is presented that exemplifies
      the ethical and legal tensions surrounding surrogate medical decision making for
      acutely ill, never-competent, profoundly intellectually disabled patients.

PMID- 22462388
TI  - Care versus treatment at the end of life for profoundly disabled persons.
AB  - Individuals who are profoundly mentally handicapped do not have the capacity to
      make their own decisions and also do not have a past record of decisions, from
      when they had capacity, to guide us in making decisions for them. They represent
      a difficult group, ethically, for surrogate decision making. Here I propose some
      guidelines, distinguishing between these patients and patients in a persistent
      vegetative state (PVS). As the life span of patients becomes shorter, or their
      level of consciousness becomes permanently impaired, the presumption for comfort
      care should become an imperative, and the standard of evidence to justify any
      invasive intervention should become higher. For members of this population, who
      have no more ability to refuse treatment than to consent to it, protection of the
      vulnerable must mean allowing a peaceful death as well as a comfortable life.
      Reasonable legal safeguards are also proposed to allow improved end-of-life
      decisions to be made for this population.

PMID- 22462389
TI  - Legal briefing: The unbefriended: making healthcare decisions for patients
      without surrogates (Part 1).
AB  - This issue's "Legal Briefing" column covers recent legal developments involving
      medical decision making for unbefriended patients. These patients have neither
      decision-making capacity nor a reasonably available surrogate to make healthcare
      decisions on their behalf. This topic has been the subject of recent articles in
      JCE. It has been the subject of major policy reports. Indeed, caring for the
      unbefriended has even been described as the "single greatest category of
      problems" encountered in bioethics consultation. Moreover, the scope of the
      problem continues to expand, especially with rapid growth in the elderly
      population and with an increased prevalence of dementia. Unfortunately, most U.S.
      jurisdictions have failed to adopt effective healthcare decision-making systems
      or procedures for the unbefriended. "Existing mechanisms to address the issue of
      decision making for the unbefriended are scant and not uniform". Most providers
      are "muddling through on an ad hoc basis". Still, over the past several months, a
      number of state legislatures have finally addressed the issue. These developments
      and a survey of the current landscape are grouped into the following 14
      categories. The first two define the problem of medical decision making for the
      unbefriended. The remaining 12 categories describe different solutions to the
      problem. The first six of these solutions are discussed in this article (Part 1).
      The last eight solutions will be covered in the Summer 2012 issue of JCE (Part
      2). 1. Who are the unbefriended? 2. Risks and problems of the unbefriended. 3.
      PREVENTION: advance care planning, diligent searching, and careful capacity
      assessment. 4. Decision-making mechanisms and standards. 5. Emergency exception
      to informed consent. 6. Expanded default surrogate lists: close friends. 7.
      Private guardians. 8. Volunteer guardians. 9. Public guardians. 10. Temporary and
      emergency guardians. 11. Attending physicians. 12. Other clinicians, individuals,
      and entities. 13. Institutional committees. 14. External committees.

PMID- 22462391
TI  - Sample treatment considerations in the analysis of organic colorants by surface
      enhanced Raman scattering.
AB  - The introduction of surface-enhanced Raman spectroscopy (SERS) in the field of
      cultural heritage has significantly improved the analysis of the organic dyes and
      their complexes that have been used as textile dyes and pigments in paintings and
      other polychrome works of art since antiquity. Over the last five years, a number
      of different procedures have been developed by various research groups. In this
      Article, we evaluate the effect of pretreating samples by exposing them to
      hydrofluoric acid (HF) vapor prior to SERS analysis, a step designed to hydrolyze
      the dye-metal complexes and increase analyte adsorption on the nanosized metallic
      support, thus enhancing the SERS signal. Materials studied include pure
      colorants, commercial lake pigments, and fibers from dyed textiles, as well as
      actual aged samples, such as microscopic fragments of lakes on paper and ancient
      pigments and glazes from several works of art, covering a wide range of time,
      from the second century B.C. to the early 20th century. In each case, SERS
      spectra obtained with or without HF hydrolysis were critically evaluated. The
      pretreatment with HF vapor resulted in faster analysis and increased sensitivity
      in most cases, with the exception of dyed silk fibers, where silk protein
      hydrolyzates were found to interfere with SERS analysis. As a final point, a two
      step procedure including SERS on untreated and treated samples is proposed as a
      standard approach: by analyzing a sample first without hydrolysis, and then,
      following removal of the colloid, upon HF treatment, the best and most reliable
      results for a great number of dyes and substrates are assured.

PMID- 22462390
TI  - Biochemical analysis and in vivo hypoglycemic activity of a grape polyphenol
      soybean flour complex.
AB  - Defatted soybean flour (DSF) can efficiently sorb, concentrate, and stabilize
      polyphenols, but not sugars, from Concord grape juice, to yield grape polyphenol
      enriched DSF. Sorption of grape polyphenols to DSF particles was dependent on the
      ratio of DSF and grape juice concentrate used, but not time of mixing or pH.
      Depending on ratios of starting materials, 1 g of grape polyphenol-enriched DSF
      contained 1.6-10.4 mg of anthocyanins, 7.5-93.1 mg of proanthocyanidins, and 20.5
      144.5 mg of total polyphenols. LC-MS analysis of grape juice samples before and
      after addition and removal of DSF and eluate from grape polyphenol-enriched DSF
      confirmed that a broad range of grape compounds were sorbed to the DSF matrix.
      Finally, grape polyphenol-enriched DSF was able to significantly lower blood
      glucose levels in hyperglycemic C57BL/6J mice. The data indicate that grape
      polyphenol-enriched DSF can provide a high-protein, low-sugar ingredient for
      delivery of concentrated grape polyphenolics.

PMID- 22462392
TI  - Time dependent effect on mortality of drug-eluting stents versus bare metal
      stents.
AB  - OBJECTIVE: The comparison of all-cause long-term mortality between the use of
      drug-eluting stents versus bare metal stents in patients treated with
      percutaneous coronary interventions. DESIGN: Observational data from patients
      treated at Feiring Heart Clinic from 1999 until 2010 with a follow-up of survival
      at March 8, 2011. The survival was compared using Cox regression with ordinary
      covariates, propensity score used as covariate and 1:1 propensity score matching.
      RESULTS: The analyses included 5690 patients treated solely with bare metal
      stents and 2916 with drug-eluting stents. During the study period (October 2002
      to March 2011), 996 deaths were observed. Due to nonproportional hazard effect on
      mortality of drug-eluting stents compared to bare metal stents, a landmark
      analysis splitting time at 9 months was employed. All analyses indicated a
      significantly reduced mortality by drug-eluting stents in the first 9 months with
      hazard ratios ranging from 0.42 to 0.51 with no difference in mortality from 9
      months to 8 years of follow-up. CONCLUSIONS: Short-term mortality was
      significantly reduced in the drug-eluting stent group compared to the bare metal
      stent group. A selection bias could not be ruled out as an explanation for this
      effect. No difference was observed in mortality after 9 months.

PMID- 22462393
TI  - Hyperprolactinemia as a rare cause of hypertension in chronic renal failure.
AB  - Chronic renal failure (CRF) is associated with a high risk for hypertension. An
      individualized treatment should be initiated after the diagnosis of hypertension
      and underlying etiology. Many metabolic and endocrinal abnormalities are
      encountered in CRF. We present an 11-year-old boy with CRF developing
      galactorrhea and hyperprolactinemia associated with alpha-methyldopa, defective
      dopaminergic control, and resistance to multi-antihypertensive therapy.
      Cabergoline, a dopamine receptor agonist, was effectively used in the treatment
      of hypertension. It is important to remember that sometimes treatment of an
      illness becomes the cause of this illness.

PMID- 22462394
TI  - Synthesis of nonspherical superparamagnetic particles: in situ coprecipitation of
      magnetic nanoparticles in microgels prepared by stop-flow lithography.
AB  - We present the synthesis of nonspherical magnetic microparticles with multiple
      functionalities, shapes, and chemistries. Particle synthesis was performed in two
      steps: polymeric microparticles functionalized homogenously with carboxyl groups
      were generated using stop-flow lithography, and then in situ coprecipitation was
      used to grow magnetic nanoparticles at these carboxyl sites. With successive
      growth of magnetic nanoparticles, we obtained polymeric particles with saturation
      magnetizations of up to 42 emu/g microparticle. The growth in the magnetic
      nanoparticle mean size and polydispersity was determined from the magnetization
      curves obtained following each growth cycle; nanoparticle sizes were limited by
      the physical constraint of the effective mesh within the hosting gel
      microparticle. Particles with spatially segregated domains of varying magnetic
      properties (e.g., Janus particles, particles with step changes in magnetite
      concentration, etc.) can be synthesized readily using this approach.

PMID- 22462396
TI  - Home-based care provision within the German welfare mix.
AB  - With the introduction of long-term care insurance (LTCI) in 1995/96, Germany
      established a universal long-term care scheme within a cost containment framework
      to provide public support in defined situations of care dependency. The scheme
      aimed to promote ageing in place with an emphasis on public support for family
      care provision as a precondition. A further aim was the expansion of market
      oriented professional care services to offer users a choice between family and
      professional care provision and care providers. The focus of this study is on the
      interplay of formal and informal family care provision within the institutional
      framework of LTCI, as well as the organisation, regulations and mix of different
      types of formal care services. In a first step, an examination of the interplay
      of formal and informal care provision shows the largely family-oriented care
      strategy, the burdened situation of informal carers, the mix of rationalities of
      service use and their interrelationship with socioeconomic inequality. In a
      second step, an analysis of the organisation of different types of formal
      services reveals paid care provision that emerges in the interplay of
      politicians' strategies to develop professional care services within the
      framework of LTCI, bottom-up strategies of users to increase the range of
      services outside the framework of LTCI and efforts of politicians to regulate the
      latter. Basic orientations of care provision underlying the development process
      such as user orientation, quality and comprehensiveness guided the process and
      are used to analyse the development. Finally, the discussion of the situation of
      care workers reveals a contradictory picture with increasing employment
      opportunities, a comparably well-qualified workforce and worsening employment
      conditions. Empirically, the research is based on an institutional analysis of
      LTCI combined with a literature review and representative statistics.

PMID- 22462395
TI  - Comparative proteomic analysis of early salt stress-responsive proteins in roots
      of SnRK2 transgenic rice.
AB  - BACKGROUND: The rice roots are highly salt-sensitive organ and primary root
      growth is rapidly suppressed by salt stress. Sucrose nonfermenting 1-related
      protein kinase2 (SnRK2) family is one of the key regulator of hyper-osmotic
      stress signalling in various plant cells. To understand early salt response of
      rice roots and identify SnRK2 signaling components, proteome changes of
      transgenic rice roots over-expressing OSRK1, a rice SnRK2 kinase were
      investigated. RESULTS: Proteomes were analyzed by two-dimensional electrophoresis
      and protein spots were identified by LC-MS/MS from wild type and OSRK1 transgenic
      rice roots exposed to 150 mM NaCl for either 3 h or 7 h. Fifty two early salt 
      responsive protein spots were identified from wild type rice roots. The major up
      regulated proteins were enzymes related to energy regulation, amino acid
      metabolism, methylglyoxal detoxification, redox regulation and protein turnover.
      It is noted that enzymes known to be involved in GA-induced root growth such as
      fructose bisphosphate aldolase and methylmalonate semialdehyde dehydrogenase were
      clearly down-regulated. In contrast to wild type rice roots, only a few proteins
      were changed by salt stress in OSRK1 transgenic rice roots. A comparative
      quantitative analysis of the proteome level indicated that forty three early salt
      responsive proteins were magnified in transgenic rice roots at unstressed
      condition. These proteins contain single or multiple potential SnRK2 recognition
      motives. In vitro kinase assay revealed that one of the identified proteome,
      calreticulin is a good substrate of OSRK1. CONCLUSIONS: Our present data
      implicate that rice roots rapidly changed broad spectrum of energy metabolism
      upon challenging salt stress, and suppression of GA signaling by salt stress may
      be responsible for the rapid arrest of root growth and development. The broad
      spectrum of functional categories of proteins affected by over-expression of
      OSRK1 indicates that OSRK1 is an upstream regulator of stress signaling in rice
      roots. Enzymes involved in glycolysis, branched amino acid catabolism, dnaK-type
      molecular chaperone, calcium binding protein, Sal T and glyoxalase are potential
      targets of OSRK1 in rice roots under salt stress that need to be further
      investigated.

PMID- 22462397
TI  - Asymmetric and highly stereoselective synthesis of the DEF-ring moiety of (-)
      FR182877 and its derivative inducing mitotic arrest.
AB  - The asymmetric and highly stereoselective synthesis of compound 1, which
      corresponds exactly to the DEF-ring moiety of (-)-FR182877, and the biological
      activities of its derivatives are described. All derivatives of 1 showed no
      activity in the tubulin polymerization assay, but one derivative was shown to
      have the ability to induce mitotic arrest by interfering with microtubule
      dynamics, and the cellular effects are similar to those of paclitaxel.

PMID- 22462398
TI  - Uptake of pyrene by NaCl, NaNO3, and MgCl2 aerosol particles.
AB  - Photoelectric charging experiments measure heterogeneous uptake coefficients for
      pyrene on model marine aerosol particles, including NaCl, NaNO(3), and MgCl(2).
      The analysis employs a multilayer kinetic model that contains adsorption and
      desorption rate constants for the bare aerosol surface and for pyrene-coated
      surfaces. First coating the aerosol particles with a pyrene layer and following
      the desorption using both t-DMA and photoelectric charging yields the desorption
      rate constants. Separate experiments monitor the increase in surface coverage of
      initially bare aerosol particles after exposure to pyrene vapor in a sliding
      injector flow tube. Analyzing these data using the multilayer model constrained
      by the measured desorption rate constants yields the adsorption rate constants.
      The calculated initial heterogeneous uptake coefficient, gamma(0)(295 K), is 1.1
      * 10(-3) for NaCl, 6.6 * 10(-4) for NaNO(3), and 6.0 * 10(-4) for MgCl(2). The
      results suggest that a free energy barrier controls the uptake rate rather than
      kinematics.

PMID- 22462399
TI  - Octahedral Metal Carbonyls. XXXV. Mechanism of the Reaction of 2,2'
      Dipyridyltetracarbonylchromium(0) with Alkyl Phosphites.

PMID- 22462400
TI  - Rapid analytical methods for on-site triage for traumatic brain injury.
AB  - Traumatic brain injury (TBI) results from an event that causes rapid acceleration
      and deceleration of the brain or penetration of the skull with an object.
      Responses to stimuli and questions, loss of consciousness, and altered behavior
      are symptoms currently used to justify brain imaging for diagnosis and
      therapeutic guidance. Tests based on such symptoms are susceptible to false
      positive and false-negative results due to stress, fatigue, and medications.
      Biochemical markers of neuronal damage and the physiological response to that
      damage are being identified. Biosensors capable of rapid measurement of such
      markers in the circulation offer a solution for on-site triage, as long as three
      criteria are met: (a) Recognition reagents can be identified that are
      sufficiently sensitive and specific, (b) the biosensor can provide quantitative
      assessment of multiple markers rapidly and simultaneously, and (c) both the
      sensor and reagents are designed for use outside the laboratory.

PMID- 22462401
TI  - Colostomy irrigation can enhance quality of life after abdominoperineal resection
      of the rectum.

PMID- 22462402
TI  - Transformation of the mouse clonal cell line R846-DP8 by Mississippi River, raw
      and finished water samples from southeastern Louisiana.  Response to Comments.

PMID- 22462403
TI  - The relationship between rebleeding after spontaneous SAH and APOE polymorphisms
      in a Chinese population.
AB  - Rebleeding leads to lots of patients' disability and mortality after spontaneous
      subarachnoid hemorrhage (SAH), but the risk factors of rebleeding have not been
      fully understood. More evidence showed apolipoprotein E (apoE protein, APOE gene)
      influenced the outcome of spontaneous SAH. In this study, we aimed to investigate
      the relationship of APOE polymorphisms with rebleeding after spontaneous SAH. A
      total of 185 patients with spontaneous SAH were involved in the current study.
      Genomic DNA was extracted from venous blood samples to identify the APOE genotype
      by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      Rebleeding was defined as acute clinical deterioration that was accompanied by
      computed tomography (CT) evidence of rebleeding in the subarachnoid space. A
      total of 21 patients occurred rebleeding in 185 patients with spontaneous SAH in
      the hospital. Data were analyzed by chi(2)-test and logistic regression analyses.
      The statistical analysis indicated no significant association between APOE
      genotype and rebleeding in a Chinese population.

PMID- 22462404
TI  - Surface crystallization of rapamycin on stents using a temperature induced
      process.
AB  - Metallic drug eluting stents (DES) are usually prepared by coating with a drug
      polymer matrix as a rate controlling diffusion barrier. However, coating
      materials may display numerous problems, thus carrier-free DES are desired, yet
      releasing drug over long period of time. For this, we are reporting a novel
      temperature induced (TI) crystallization process for coating rapamycin on stents.
      Rapamycin crystals with a defined morphology and target drug load were applied
      from supersaturated solution. This method enables fabrication of controllable and
      homogeneous crystalline coatings on stent scaffolds and allowing the drug to
      release for several weeks.

PMID- 22462405
TI  - The senses in practice: enhancing the quality of care for residents with dementia
      in care homes.
AB  - AIM: The study aimed to develop, deliver, and evaluate a training programme in
      care homes to enhance the quality of care for people living with dementia based
      on the principles of relationship-centred care expressed through the Senses
      Framework. BACKGROUND: There are increasing numbers of people living with
      dementia worldwide with a growing proportion requiring residential long-term
      care. This makes the quest for enhancing the quality of care and quality of life
      for people with dementia ever more pressing. DESIGN: A mixed-methods design was
      used adopting a Practice Development approach. The findings from one care home in
      the North West of England are reported. METHODS: Eight facilitated workshops
      based on the principles of relationship-centred care were completed and evaluated
      in 2010, using pre- and postintervention design. A focus group was undertaken
      with staff on completion of the study to gain a more comprehensive understanding
      of the practice/training context, augmented by case examples of changes in
      practice identified from the study workshops. RESULTS: Structured questionnaires
      were used to profile the care home before and after the training. Following the
      workshops, staff felt more able to collect and use biographical information. In
      particular, staff reported how this information supported them to initiate
      meaningful conversations with the person with dementia as part of everyday care
      routines, thus improving overall feelings of well-being. CONCLUSION: Using a
      biographical approach to care planning structured through the Senses Framework
      helped staff to develop a greater understanding of the person with dementia.

PMID- 22462406
TI  - A cross-sectional study on the prevalence of marginal bone loss among implant
      patients.
AB  - OBJECTIVE: The aim of the present cross-sectional retrospective study was to
      determine bone loss in a sample of subjects restored with implant-supported
      prostheses and the prevalence and severity of peri-implantitis in a sub-sample.
      MATERIAL AND METHODS: A total of 139 patients who had attended a follow-up visit
      in 2007 were considered for inclusion. Subjects with implants that had been in
      function for less than 3 years or had poor quality radiographs were excluded. The
      final study population comprised 133 subjects with a total of 407 implants.
      Radiographic measurements identified subjects who had >=1 implant site exhibiting
      marginal bone loss of >0.5 mm; 40 subjects met this criterion and were recalled
      for a clinical examination. Of the 40 subjects that were recalled for the
      clinical examination, 30 attended. The following parameters were recorded at
      mesial, distal, buccal, and lingual/palatal aspects of all implants: oral hygiene
      standard (plaque), bleeding on probing, probing pocket depth (PPD). RESULTS: The
      mean interval between the baseline (1-year post-loading) and the follow-up
      radiographs was 4.8 +/- 2.3 years. In the total subject sample (133 subjects and
      407 implants), the mean amount of marginal bone loss that had occurred was 0.2 +/
      1.2 mm. Ninety-three subjects with 246 implant sites exhibited no bone level
      alteration (group A), whereas 40 subjects with 161 implant sites (group B)
      displayed marginal bone loss of >0.5 mm at >=1 implant (loser site). Sixty-eight
      implant sites in group B exhibited bone loss of >0.5 mm. However, only 20% of
      subjects and 11% of sites had lost >1 mm marginal bone, and 8% of subjects and 4%
      of sites had lost >2 mm bone. The total amount of bone loss that had occurred in
      group B was (i) 0.88 +/- 1.5 mm and (ii) among the loser sites 2.1 +/- 1.4 mm.
      Thirty subjects from group B were exposed to a clinical examination; out of 37
      sites with bone loss >0.5 mm in this subgroup, 29 sites had a PPD value of >=4
      mm. CONCLUSION: Marginal bone loss (>0.5 mm) at implants was observed in 30% of
      subjects and 16% of implant sites. More advanced loss of marginal bone occurred
      in much fewer subjects and sites. Sites with marginal bone loss was in the sub
      sample characterized by bleeding on probing, but only occasionally with deep (>=6
      mm) pockets.

PMID- 22462407
TI  - A genetic linkage map of crested wheatgrass based on AFLP and RAPD markers.
AB  - Using a population of 105 interspecific F(2) hybrids derived from a cross between
      Agropyron mongolicum  Keng and  Agropyron cristatum  (L.) Gaertn. 'Fairway' as a
      mapping population, a genetic linkage map of crested wheatgrass was constructed
      based on AFLP and RAPD molecular markers. A total of 175 markers, including 152
      AFLP and 23 RAPD markers, were ordered in seven linkage groups. The map distance
      was 416 cM, with a mean distance of 2.47 cM between markers. The number of
      markers ranged from 13 to 46 in each linkage group and the length of groups
      ranged from 18 to 104 cM. The research found that 30 out of 175 molecular markers
      showed segregation distortion, accounting for 17% of all markers. This is the
      first genetic linkage map of crested wheatgrass. This map will facilitate gene
      localization, cloning, and molecular marker-assisted selection in the future.

PMID- 22462408
TI  - Dose-response model of murine typhus (Rickettsia typhi): time post inoculation
      and host age dependency analysis.
AB  - BACKGROUND: Rickettsia typhi (R. mooseri) is the causative agent of murine
      typhus. It is one of the most widely distributed flea-borne diseases with a
      relatively mild febrile initial illness with six to 14 days of incubation period.
      The bacterium is gram negative and an obligate intracellular pathogen. The
      disease is transmitted to humans and vertebrate host through fleabites or via
      contact with infected feces. This paper develops dose-response models of
      different routes of exposure for typhus in rodents. METHODS: Data from published
      articles were analyzed using parametric dose-response relationship models. Dose
      response relationships were fit to data using the method of maximum likelihood
      estimation (MLE). RESULTS: Dose-response models quantifying the effects of
      different ages of rats and time post inoculation in BALB/c mice were analyzed in
      the study. Both the adult rats (inoculated intradermally) and newborn rats
      (inoculated subcutaneously) were best fit by exponential models and both
      distributions could be described by a single dose-response relationship. The
      BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The
      time post inoculation analysis showed that there was a definite time and response
      relationship existed in this case. CONCLUSIONS: Intradermally or subcutaneously
      inoculated rats (adult and newborn) models suggest that less than 1 plaque
      forming unit (PFU) (1.33 to 0.38 in 95% confidence limits) of the pathogen is
      enough to seroconvert 50% of the exposed population on average. For the BALB/c
      mouse time post inoculation model, an average dose of 0.28 plaque-forming units
      (PFU) (0.75 to 0.11 in 95% confidence limits) will seroconvert 50% of the exposed
      mice.

PMID- 22462409
TI  - The role of ICT in supporting disruptive innovation: a multi-site qualitative
      study of nurse practitioners in emergency departments.
AB  - BACKGROUND: The disruptive potential of the Nurse Practitioner (NP) is evident in
      their ability to offer services traditionally provided by primary care
      practitioners and their provision of a health promotion model of care in response
      to changing health trends. No study has qualitatively investigated the role of
      the Emergency NP in Australia, nor the impact of Information and Communication
      Technology (ICT) on this disruptive workforce innovation. This study aimed to
      investigate ways in which Nurse Practitioners (NP) have incorporated the use of
      ICT as a mechanism to support their new clinical role within Emergency
      Departments. METHODS: A cross-sectional qualitative study was undertaken in the
      Emergency Departments (EDs) of two large Australian metropolitan public teaching
      hospitals. Semi-structured, in-depth interviews were conducted with five nurse
      practitioners, four senior physicians and five senior nurses. Transcribed
      interviews were analysed using a grounded theory approach to develop themes in
      relation to the conceptualisation of the ED nurse practitioner role and the
      influences of ICT upon the role. Member checking of results was achieved by
      revisiting the sites to clarify findings with participants and further explore
      emergent themes. RESULTS: The role of the ENP was distinguished from those of
      Emergency nurses and physicians by two elements: advanced practice and holistic
      care, respectively. ICT supported the advanced practice dimension of the NP role
      in two ways: availability and completeness of electronic patient information
      enhanced timeliness and quality of diagnostic and therapeutic decision-making,
      expediting patient access to appropriate care. The ubiquity of patient data
      sourced from a central database supported and improved quality of communication
      between health professionals within and across sites, with wider diffusion of the
      Electronic Medical Record holding the potential to further facilitate team-based,
      holistic care. CONCLUSIONS: ICT is a facilitator through which the disruptive
      impact of NPs can be extended. However, integration of ICT into work practices
      without detracting from provider-patient interaction is crucial to ensure
      utilisation of such interventions and realisation of potential benefits.

PMID- 22462410
TI  - Targeted parallel sequencing of large genetically-defined genomic regions for
      identifying mutations in Arabidopsis.
AB  - Large-scale genetic screens in Arabidopsis are a powerful approach for molecular
      dissection of complex signaling networks. However, map-based cloning can be time
      consuming or even hampered due to low chromosomal recombination. Current
      strategies using next generation sequencing for molecular identification of
      mutations require whole genome sequencing and advanced computational devises and
      skills, which are not readily accessible or affordable to every laboratory. We
      have developed a streamlined method using parallel massive sequencing for mutant
      identification in which only targeted regions are sequenced. This targeted
      parallel sequencing (TPSeq) method is more cost-effective, straightforward enough
      to be easily done without specialized bioinformatics expertise, and reliable for
      identifying multiple mutations simultaneously. Here, we demonstrate its use by
      identifying three novel nitrate-signaling mutants in Arabidopsis.

PMID- 22462411
TI  - Altered microRNA expression profile in maternal and fetal liver of HBV transgenic
      mouse model.
AB  - OBJECTIVE: MicroRNAs (miRNAs) regulate gene expression in a post-transcriptional
      sequence-specific manner. Expression profile analysis of miRNAs in liver is
      necessary to understand the possible roles of miRNAs in hepatitis B virus (HBV)
      infection. METHODS: We obtained HBV-positive liver samples from mice, using HBV
      transgenic mouse model. MicroRNA expression was analyzed with Agilent microRNA
      Array and validated using quantitative real-time PCR analysis. RESULTS: RNA
      samples from liver of HBV transgenic mouse liver exhibited notably different miR
      profiles from negative controls for both maternities and fetuses. Significant
      differences in expression profile of miRNAs were also found in fetal and maternal
      group of HBV transgenic mouse model. Expression of miR-1892 and miR-1187
      decreased by approximately 2-fold (p < 0.01), whereas expression of miR-92a
      increased by more than 6-fold (p < 0.001) in the fetal group, as validated by
      qPCR. CONCLUSION: Deregulation of miRNAs expression in fetal livers could be
      implicated in HBV intrauterine infection. Further study is warranted to identify
      the target genes of these miRNAs and their function. Besides, these data might
      offer new ideas for blocking HBV intrauterine infection.

PMID- 22462412
TI  - What would 5-HT do? Regional diversity of 5-HT(1)  receptor modulation of primary
      afferent neurotransmission.
AB  - 5-HT (serotonin) is a significant modulator of sensory input to the CNS, but the
      only analgesics that selectively target G-protein-coupled 5-HT receptors are
      highly specific for treatment of headache. Two recent papers in BJP shed light on
      this puzzling situation by showing that primary afferent neurotransmission to the
      superficial layers of the spinal and trigeminal dorsal is inhibited by different
      subtypes of the 5-HT(1) receptor - 5-HT(1B(and 1D) ) in the trigeminal dorsal
      horn and 5-HT(1A) in the spinal dorsal horn. The inputs being studied probably
      include nociceptive afferents, and the similarities of the methods employed in
      the two studies minimize the possibility that the different findings are an
      experimental artefact. Rather, the findings raise interesting questions about the
      possible anatomical or functional basis for the apparent regional selectivity of
      5-HT(1) receptor actions, and whether these differences could be exploited for
      therapy. The results also emphasize the relative lack of information we have
      about the molecular details of the pro- or anti-nociceptive actions of 5-HT
      itself on primary afferent neurotransmission.

PMID- 22462414
TI  - Editorial response to "management of intracranial hemorrhage in a child with a
      left ventricular assist device".

PMID- 22462415
TI  - Conducting a meta-analysis: basics and good practices.
AB  - Meta-analysis is a statistical method to compare and combine effect sizes from a
      pool of relevant empirical studies. It is now a standard approach to synthesize
      research findings in many disciplines, including medical and healthcare research.
      This paper is the third paper of a mini-series introducing systematic review and
      meta-analysis. First, common effect sizes used in meta-analysis are presented.
      Fixed-, random- and mixed-effects models are then introduced. Next, a real data
      set from a published meta-analysis will be used to illustrate the procedures and
      interpretations. Last, software packages that may be used to conduct meta
      analyses will be highlighted.

PMID- 22462413
TI  - Changes in nucleus accumbens and neostriatal c-Fos and DARPP-32 immunoreactivity
      during different stages of food-reinforced instrumental training.
AB  - Nucleus accumbens is involved in several aspects of instrumental behavior,
      motivation and learning. Recent studies showed that dopamine (DA) release in the
      accumbens shell was significantly increased on the first day of training on a
      fixed ratio (FR) 5 schedule (i.e. the transition from FR1 to FR5) compared with
      those rats that continued FR1 training, even though the rats on their first day
      of FR5 training received less food reinforcement than rats continuing on the FR1
      schedule. Additionally, the second day of FR5 responding was marked by a
      significant increase in DA release in accumbens core. The present studies
      employed immunohistochemical methods to characterize the changes in cellular
      markers of accumbens and neostriatal neural activity that occur during various
      stages of food-reinforced FR5 training. c-Fos and DARPP-32 immunoreactivity in
      accumbens shell was significantly increased on the first day of FR5 training,
      while core c-Fos and DARPP-32 expression showed large increases on the second day
      of FR5 training. Additional studies showed that c-Fos and DARPP-32 expression in
      neostriatum increased after more extensive training. Double-labeling studies with
      immunofluorescence methods indicated that increases in accumbens c-Fos and DARPP
      32 expression were primarily seen in substance-P-positive neurons. These
      increases in accumbens c-Fos and DARPP-32 immunoreactivity seen during the
      initial phases of FR training may reflect several factors, including novelty,
      learning, stress or the presentation of a work-related challenge to the organism.
      Moreover, it appears that the separate subregions of the striatal complex are
      differentially activated at distinct phases of instrumental training.

PMID- 22462416
TI  - High burden of rheumatic diseases in Lebanon: a COPCORD study.
AB  - AIM: To estimate the prevalence of rheumatic diseases in Lebanon and to explore
      their distribution by geographic location, age, and gender. METHOD:   Using the
      Community Oriented Program for the Control of Rheumatic Diseases (COPCORD)
      methodology, a random sample of 3530 individuals aged 15 and above was
      interviewed from the six Lebanese governorates. Positive respondents were
      evaluated by rheumatologists using the internationally accepted classification
      criterion of the American College of Rheumatology for the diagnosis of rheumatic
      diseases. RESULTS: Prevalence rates of current and past musculoskeletal problems
      were 24.4% and 8.4%, respectively. Shoulder (14.3%), knee (14.2%) and back
      (13.6%) were the most common pain sites. Point prevalence of rheumatic diseases
      was 15.0%. The most frequent types of rheumatic diseases were of mechanical
      origin, namely soft tissue rheumatism (5.8%) and osteoarthritis (4.0%).
      Rheumatoid arthritis (1.0%) and spondylathropathies (0.3%) constituted the most
      common inflammatory diseases. Coastal areas had the lowest prevalence of all
      diseases except for fibromyalgia. All diseases showed an increasing prevalence
      pattern with age and a higher prevalence among women than men. CONCLUSION: This
      is the first study to give population-based estimates of rheumatic diseases in
      Lebanon. The high burden calls for public health attention for early detection,
      control and prevention of these conditions. Point prevalence of individual
      diseases was within the range of results from other COPCORD surveys with some
      variations that can be attributed to differences in methodology and geo-ethnic
      factors.

PMID- 22462417
TI  - The efficacy of Back School on chronic low back pain of workers of a
      pharmaceutical company in a Tehran suburb. COPCORD stage II study.
AB  - AIM: Low back pain (LBP) is the second most frequent reason for seeking medical
      advice. Various treatments are proposed from no intervention, to analgesics,
      rest, exercises, local interventions and surgical procedures. Results and
      outcomes are differently reported. Back School (BS), a combination of patient
      education and physical exercises, seems to have good results. The aim of this
      study was to check the effect of BS in factory workers. PATIENTS AND METHODS: All
      (70) workers were interviewed and 26 of them (37.1%) had chronic LBP. Secondary
      causes were excluded. Anatomy, physiology, biomechanics of the spine, correct
      postures at work and back exercises were taught. Pain on a visual analog scale
      (VAS) of 0-100, and Short Form (SF)-36 health survey were applied, before, at the
      end of BS sessions, and 3 months after BS. Analysis was done by t-test, Wilcoxon
      and Pearson's correlation test. RESULTS: The mean VAS on pain before BS was 43.4
      +/- 22.3, improving to 38.6 +/- 17.5 at the end of BS. The difference was not
      significant (P = 0.19). The mean VAS improved to 27.5 +/- 20 at 3 months after
      BS. The difference was significant compared to before BS (P = 0.001). The quality
      of life measured by the SF-36 questionnaire, did not improve significantly,
      except for two of its eight subgroups (Role Physical, Social Functioning) at the
      end of BS, and two of its subgroup (Mental Health, Social Functioning) at 3
      months after BS. CONCLUSION: Among industrial workers, BS is mainly effective on
      pain, but is less evident on SF-36.

PMID- 22462418
TI  - Different clinical features in patients with ankylosing spondylitis from southern
      and northern China.
AB  - AIMS: To describe clinical features of patients with ankylosing spondylitis (AS)
      from southern and northern China, and investigate the effects of onset age,
      gender and regional differences on disease phenotype. METHODS: Totally 113 AS
      patients from southern China and 121 AS patients from northern China were
      analyzed retrospectively. RESULTS: In southern and northern groups, low back pain
      was more frequent among initial symptoms (54.9% vs. 7.7%; 52.4% vs. 11.4%), while
      peripheral arthritis (15.7% vs. 35.9%; 22.2% vs. 68.6%) was less common in male
      adult AS (AAS) than in male juvenile AS (JAS) patients, respectively. Compared to
      those in the northern group, diagnostic delay was longer (7.3 vs. 3.5 years) and
      the prevalence of human leukocyte antigen (HLA)-B27 was higher in the southern
      group (96.5% vs. 83.5%). Sacroiliitis grade 2 was more frequent (51.3% vs.
      36.4%), while sacroiliitis grade 3 (32.7% vs. 53.7%), buttock pain (5.3% vs.
      13.2%), knee (20.4% vs. 33.1%) and ankle (3.5% vs. 11.6%) arthritis were less
      frequent in the southern group. Diagnostic delay of southern JAS was longer than
      that of northern JAS regardless of gender. Both sacroiliitis grade 3 and
      peripheral arthritis were less frequent in southern male JAS than in northern
      male JAS. Diagnostic delay was longer, sacroiliitis grade 2 was more frequent,
      while sacroiliitis grade 3 was less frequent in southern male AAS than those in
      northern male AAS. CONCLUSION: Significant diagnostic delay and higher prevalence
      of HLA-B27 were found in southern AS patients. The prevalence of buttock pain and
      peripheral arthritis at disease onset in northern AS was more frequent than in
      southern AS patients.

PMID- 22462419
TI  - Distinct impacts of syndesmophyte formation on male and female patients with
      ankylosing spondylitis.
AB  - AIM: Ankylosing spondylitis (AS), a chronic inflammatory autoimmune disease,
      mainly affects the axial skeleton, leading to sacroiliitis and rigidity of the
      spine. Both spinal rigidity and syndesmophyte development can affect bone
      formation and resorption. In addition, inflammatory cytokines and cell adhesion
      molecules are correlated with bone metabolism. The aim of this study was to
      investigate the effects of gender difference and syndesmophyte formation on
      cytokines, adhesion molecules and bone metabolism markers in AS patients. METHOD:
      Eighty-seven AS patients (68 males, 19 females) were enrolled in this study.
      Electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay were
      performed to measure studied parameters. RESULTS: Regarding gender, the serum
      levels of C-terminal crosslinking telopeptide of type I collagen (CTX), vascular
      endothelial growth factor, soluble vascular cell adhesion molecule-1, tumor
      necrosis factor alpha and interleukin (IL)-18 in male patients were all
      significantly higher than those in female patients. The serum levels of
      osteocalcin and type I procollagen N-terminal propeptide showed downward trends,
      whereas CTX and parathyroid hormone concentrations were remarkably lower and IL
      18 levels were significantly higher in male AS patients with syndesmophytes
      compared to those without syndesmophytes. In female patients, CTX and IL-6 levels
      in those with syndesmophytes were significantly higher than in those without
      syndesmophytes. Cytokines, adhesion molecules and bone metabolism markers were
      all positively related with syndesmophyte formation and gender differences.
      CONCLUSION: AS patients with syndesmophytes experienced imbalance of bone
      metabolism due to inflammatory cytokine release. Male AS patients had high levels
      of bone resorption markers, cytokines and adhesion molecules, reflecting a
      disorder of bone metabolism.

PMID- 22462420
TI  - Proteomic analysis of bone marrow-adherent cells in rheumatoid arthritis and
      osteoarthritis.
AB  - AIM: To elucidate the pathophysiology of rheumatoid arthritis (RA) as well as
      osteoarthritis (OA), we analyzed protein profiles of bone marrow-derived adherent
      cells (BMACs) from patients with these diseases. METHODS: Proteins, extracted
      from BMACs from three RA and three OA patients, were comprehensively analyzed by
      2-dimensional differential image gel electrophoresis (2D-DIGE). Then a part of
      the detected proteins, differently expressed between the two diseases, were
      identified by mass spectrometric analysis. RESULTS: 2D-DIGE analysis detected
      more than 1600 protein spots in both RA and OA BMACs. Out of these, expression of
      340 spots was significantly altered between the diseases (more than 1.5-fold: RA
      > OA, 26 spots; OA > RA, 314 spots; P < 0.05). Eleven protein spots the intensity
      of which were significantly altered by more than 2.0-fold were identified, which
      included vimentin and annexin A5 as increased proteins in RA rather than in OA.
      As increased proteins in OA compared to RA, alpha chain of collagen VI, a
      membrane anchor for acetylcholine esterase, heat shock protein 27, caldesmon and
      cytoskeletal proteins, such as beta actin and alpha tubulin, were identified.
      CONCLUSIONS: We here report different protein profiles of BMACs between RA and OA
      for the first time. BMACs possessing differently expressed proteins may be
      involved in the pathophysiology of the two diseases.

PMID- 22462421
TI  - Tumor markers are elevated in patients with rheumatoid arthritis and do not
      indicate presence of cancer.
AB  - AIM: To investigate serum levels of tumor markers in patients with rheumatoid
      arthritis (RA) and their association with disease activity or the presence of
      cancer. METHOD: We performed an observational cohort study including 100 patients
      with RA and control subjects. Serum levels of tumor markers carcinoembryonic
      antigen (CEA), cancer antigen (CA) 125, CA 19-9 and CA 15-3 were evaluated along
      with clinical and laboratorial RA data. Association tests between tumor markers
      levels and RA disease activity parameters were performed. Patients with abnormal
      tests were submitted to further investigation, including chest X-ray,
      colonoscopy, abdominal ultrasonography, upper gastrointestinal endoscopy and
      mammography, depending on the type of tumor marker that was elevated. RESULTS:
      Patients with RA had high levels of CEA and CA 19-9 more frequently than controls
      (P < 0.05). No correlation was found between tumor markers and RA disease
      activity assessed by the Disease Activity Score 28. Two neoplasms were found, but
      only one was related to high tumor marker (an ovarian carcinoma with high CA 125
      levels). CONCLUSION: High tumor markers were frequently found in RA patients,
      even with controlled disease and were not related to actual cancer. Therefore,
      small increases of these markers in RA cases probably do not warrant a search for
      an occult neoplasm.

PMID- 22462422
TI  - The role of interleukin (IL)-17 in anxiety and depression of patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Pro-inflammatory cytokines are found to be elevated in patients with
      anxiety and depression but whether their serum levels are related to anxiety and
      depression is unknown. We used rheumatoid arthritis (RA) as an inflammatory
      disease model to explore such relationships. METHODS: Eighteen RA patients and 18
      healthy controls matched for age and gender were assessed for the severity of
      anxiety and depression with the hospital anxiety and depression scale (HADS).
      Disease activity of RA and pain were assessed by the Disease Activity Scale (DAS
      2)8 and visual analogue scale of pain, respectively. Serum pro-inflammatory
      cytokine levels, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6
      and IL-17 were determined by enzyme-linked immunosorbant assay. The differences
      in cytokine levels between RA patients and healthy controls, as well as within
      the RA group with and without anxiety and depression, were compared by using the
      Mann-Whitney U-test. The correlations between anxiety, depression and pro
      inflammatory cytokines were explored by Spearman's rank correlation. Multiple
      linear regression was used to adjust for DAS-28 and pain. RESULTS: Serum TNF
      alpha, IL-6 and IL-17 levels were significantly higher in RA patients than those
      of healthy subjects (P < 0.001, P = 0.012 and P = 0.016, respectively). Within
      the RA group, serum IL-17 level was significantly higher in those with anxiety
      than those without (P = 0.044). Additionally, IL-17 level was positively
      correlated with the severity of anxiety, even after adjustment for DAS-28 and
      pain. CONCLUSION: Serum IL-17 was elevated in RA patients, especially in those
      with anxiety. In addition, IL-17 level was independently associated with higher
      anxiety score.

PMID- 22462424
TI  - Therapeutic ultrasound versus sham ultrasound for the management of patients with
      knee osteoarthritis: a randomized double-blind controlled clinical study.
AB  - AIM: The aim of this trial was to evaluate the short-term effectiveness of
      ultrasound (US) therapy on pain, physical function, ambulation activity,
      disability and psychological status in patients with knee OA. METHODS: Forty-two
      inpatients with bilateral knee OA were randomized by an independent researcher
      not involved in the data assessment, to receive either therapeutic continuous US
      (group 1) or sham US (group 2). A 1-MHz US head was used, set to an intensity of
      1 W/cm(2) for 10 min. All patients received 20 min of hot packs, 10 min of
      interferential current, and 15 min of quadriceps isometric exercise of both
      knees. Patients in each group received treatments five times weekly for 3 weeks.
      Patients were evaluated at baseline and at the end of the treatment sessions.
      Outcome measures included visual analogue scale (VAS), Western Ontario and
      McMaster University Osteoarthritis Index (WOMAC), 50-m walking speed, Lequesne
      index, Hospital Anxiety and Depression Scale (HADS). RESULTS: The patients with
      knee OA had significant improvements in pain, stiffness, functional activity,
      walking time, disability, depression and anxiety scores with therapeutic US and
      sham US (P < 0.05). The improvement in pain VAS scores, WOMAC scores, Lequesne
      index and HADS scores were not significantly different in patients treated with
      US and sham US (P > 0.05). No side-effects were reported during or after the US
      treatment periods. CONCLUSION: US therapy is safe but use of US in addition to
      conventional physical therapy programs seems to have no further significant
      effect in people with knee OA.

PMID- 22462423
TI  - Randomized comparison of etanercept with usual therapy in an Asian population
      with active rheumatoid arthritis: the APPEAL trial.
AB  - AIM: Rheumatoid arthritis (RA) is an important rheumatologic disease in Asia
      Pacific countries, as in other parts of the world. However, limited information
      is available regarding RA therapy in this region. The Asia-Pacific Study in
      Patients to be Treated With Etanercept or an Alternative Listed DMARD (APPEAL)
      compared efficacy and safety of etanercept (ETN) + methotrexate (MTX) versus
      usual disease-modifying anti-rheumatic drugs (DMARDs) + MTX (reflecting regional
      practice) in subjects with moderate to severe RA from multiple Asia-Pacific
      countries. METHOD: In this open-label, active-comparator, parallel-design,
      multicenter study, subjects (n = 300) in the Asia-Pacific region were randomized
      to ETN + MTX (n = 197) or DMARD + MTX (n = 103). The primary efficacy endpoint
      was the American College of Rheumatology (ACR) response (ACR-N) area under the
      curve (AUC) over 16 weeks. RESULTS: Baseline characteristics were similar between
      groups. At Week 16, ACR-N AUC indicated a significantly greater response with ETN
      + MTX compared with DMARD + MTX (mean difference -145.3; P < 0.001).
      Significantly greater proportions of subjects achieved ACR 20, 50 and 70
      responses with ETN + MTX versus DMARD + MTX at Week 16 (P < 0.05). Low Disease
      Activity Score based on a 28-joint count (DAS28 < 3.2) was also achieved by
      significantly more subjects in the ETN + MTX group versus the DMARD + MTX group
      (P < 0.001). Greater improvements were shown for DAS28, pain visual analogue
      scale, health assessment questionnaire, and physician and patient global
      assessments (P < 0.05) for ETN + MTX versus DMARD + MTX. No new safety signals
      were found. CONCLUSION: In this Asia-Pacific population of subjects with moderate
      to severe RA, ETN + MTX showed superior efficacy versus usual DMARD + MTX
      regimens, with similar safety profiles.

PMID- 22462425
TI  - The effect of non-steroidal anti-inflammatory drugs on the endothelial function
      of patients with osteoarthritis in short term.
AB  - OBJECTIVE: Our primary aim was to test whether non-steroid anti-inflammatory drug
      (NSAID) use may account for endothelial dysfunction (ED) in the acute period.
      Additionally, we also aimed to compare the effect of diclofenac and naproxen on
      endothelial function. METHODS: Forty patients with osteoarthritis (OA) were
      included in the study. Subjects currently receiving NSAIDs were asked to
      discontinue their anti-inflammatory medications (for at least 5 days) before the
      study. After the wash-out period, all subjects underwent vascular ultrasound
      measurements. Following baseline vascular imaging, patients were randomly
      assigned in a 1 : 1 ratio to receive either diclofenac (75 mg twice daily, n =
      20), or naproxen (500 mg twice daily, n = 20) for 7 days. Endothelial function
      was evaluated by using the flow-mediated dilatation (FMD) method, at baseline,
      and after 1 week of NSAID treatment. RESULTS: There were 40 OA patients (4 male,
      36 female). The median age of the patients was 60 +/- 14 years. There were equal
      numbers of subjects in each treatment group. Age, sex distribution, body mass
      index, serum lipids, erythrocyte sedimentation rate, C-reactive protein and
      fasting glucose levels were similar between the diclofenac and naproxen groups (P
      > 0.05). The brachial artery diameter (BAD), endothelium-dependent vasodilatation
      (FMD%) and nitroglycerin-induced endothelium-independent vasodilatation (NTG%)
      values were not different between pretreatment and on the seventh day in the
      NSAID treatment groups (P > 0.05). Subgroup analysis also showed similar values
      of BAD, FMD%, and NTG% between naproxen and diclofenac groups (P > 0.05).
      CONCLUSION: Our results suggest that nonselective cyclo-oxygenase antagonists
      naproxen and diclofenac have no effect on endothelial function during short-term
      use.

PMID- 22462426
TI  - Comprehensive analysis of transcription factor expression patterns in peripheral
      blood mononuclear cell of systemic lupus erythematosus.
AB  - BACKGROUND: Transcription factors (TFs) play a central role in regulating gene
      expression and in providing interconnecting regulatory networks between related
      pathway elements. Systemic lupus erythematosus (SLE) is an organ-nonspecific
      autoimmune disorder characterized by the production of autoantibodies against a
      host of nuclear antigens. AIM: The pathogenesis of lupus is incompletely
      understood. Understanding the mechanisms that contribute to SLE and finding
      effect biomarkers to anticipate SLE will be of great value. METHOD: To
      investigate possible mechanisms, we describe a comparison of TF activity profiles
      between SLE and controls. Through TF assay analysis and electrophoretic mobility
      shift assay (EMSA) confirmation, we identified different activities of TFs in
      SLE. RESULTS: Three hundred and forty-five TFs were detected in both groups, with
      92 of them differentially expressed by TF array in which 78 TFs up-regulated and
      14 TFs down-regulated in SLE compared with the control group, while 253 TFs
      showed no significant expression levels. The array data was consistent with the
      EMSA verification results. CONCLUSION: Our data indicated that TFs may be
      potentially involved in the pathogenesis of SLE, and can help to diagnose, treat
      and prevent SLE. The method could simplify the assay of multiple TFs and may
      facilitate high-throughput profiling of large numbers of TFs.

PMID- 22462428
TI  - Acquired factor V inhibitor in systemic vasculitis.

PMID- 22462429
TI  - Anti-Golgi autoantibodies: prevalence and disease associations in a rheumatic
      disease population.

PMID- 22462430
TI  - Recurrent ventricular tachycardia in a child with juvenile dermatomyositis - an
      unusual association.

PMID- 22462431
TI  - Retinitis preceding systemic lupus erythematosus in absence of anti-phospholipid
      antibodies.

PMID- 22462432
TI  - Extremely high salivary beta(2) -microglobulin and Na(+)  levels in a Sjogren
      syndrome patient.

PMID- 22462433
TI  - A fulminant neurologic presentation of systemic lupus erythematosus.

PMID- 22462434
TI  - The medical odyssey of a boy with arthritis of familial Mediterranean fever.

PMID- 22462435
TI  - Mesenteric panniculitis: a rare cause of fever.

PMID- 22462436
TI  - Development and acceptability of a novel milk-free soybean-maize-sorghum ready-to
      use therapeutic food (SMS-RUTF) based on industrial extrusion cooking process.
AB  - Peanut milk-based ready-to-use therapeutic food (P-RUTF) primarily used to treat
      severe acute malnutrition at community setting is expensive. We developed an
      alternative milk-free soybean-maize-sorghum-based RUTF (SMS-RUTF) using locally
      grown ingredients that have the potential to support local economy and reduce the
      cost of RUTF. We describe the production process and results of acceptability of
      the new product. Acceptability and tolerance of SMS-RUTF was compared with P-RUTF
      among 45 children aged 4-11 years old based on a cross-over design. Each child
      consumed 250 g RUTF for 10 days followed by a five-day washout period and a
      subsequent 10-day period on the second RUTF. The SMS-RUTF was as acceptable as
      the P-RUTF among normal children aged 4-11 years of age with no associated
      adverse effects. SMS-RUTF was stable for at least 12 months without detectable
      microbiological or chemical deterioration. The major challenge encountered in SMS
      RUTF development was the difficulty to accurately determine key nutrient
      composition due to its high oil content. Use of diversified locally available
      ingredients to produce RUTF is feasible. The SMS-RUTF meets expected standards
      and is acceptable to children aged 4-11 months old. Effectiveness and cost
      effectiveness of SMS-RUTF is required.

PMID- 22462437
TI  - Closing the health gaps.

PMID- 22462438
TI  - Public health hazards in Poland posed by foodstuffs contaminated with E. coli
      O104:H4 bacterium from the recent European outbreak.
AB  - Shiga toxin producing Escherichia coli (STEC) are the most virulent
      diarrhoeagenic E. coli known to date. They can spread with alarming ease via the
      food chain, as recently demonstrated by the large outbreak of STEC O104:H4 borne
      by sprouted seeds in 2011, clustered in northern Germany, and subsequently
      affecting other countries. Indeed, a significant number of infections to
      verocytotoxin producing Escherichia coli O104:H4 have been reported from the WHO
      European Region resulting in many cases of bloody diarrhoea and haemolytic
      uraemic syndrome in Germany, 15 other European countries and North America.
      Eventually, the European Food Standards Agency, (EFSA), identified the likely
      source to a single consignment of fenugreek seeds from an Egyptian exporter as
      being linked to the two outbreaks in Germany and France. The situation was
      closely monitored by the Chief Sanitary Inspectorate public health authority in
      Poland where actions undertaken ensured that the public was well informed about
      the dangers of STEC contamination of food, how to avoid infection, and what to do
      if infected. Tracing the fenugreek distributors also enabled the identification
      of suspected batches and their isolation. As a result, there were very few
      reported cases of STEC infection in Poland. Effective control over such outbreaks
      is therefore a vital public health task. This should include early detection and
      rapid identification of the contagion mode, followed by removing the foodstuff(s)
      from the market, providing consumer advice, and preventing secondary spreading.
      As a mitigation measure, screening/monitoring those involved in food handling is
      also warranted to exclude carriers who can be asymptomatic.

PMID- 22462439
TI  - Influence of environment exposures on the frequency of contact allergies in
      children and adolescents.
AB  - Contact allergy is detected in every second child with the symptoms of chronic or
      recurrent eczema, and in every third child the final diagnosis is allergic
      contact dermatitis. Haptens responsible for the majority of contact
      sensitizations in children are substances ubiquitous in our environment, e.g.
      metals, preservatives, fragrances, propolis, and balsam of Peru. Much concern is
      provoked by the higher rates of sensitization to fragrances in younger children,
      compared to adolescents, which may be attributed to the higher exposure nowadays
      of infants and children to fragrant products. On the other hand, a limitation of
      exposure to the preservatives thimerosal and Kathon CG has resulted in decreased
      rates of sensitization to these haptens. Altogether, these observations
      demonstrate that the rates of contact sensitizations in children reflect changes
      in their environment, and limitations imposed on the use of haptens with strong
      sensitizing properties, may be an effective tool in the prevention of contact
      allergy.

PMID- 22462440
TI  - Occupational exposure to carbon dioxide, ammonia and hydrogen sulphide on
      livestock farms in north-west Spain.
AB  - The influence of the type of farming on harmful gas exposures to carbon dioxide
      (CO(2)), ammonia (NH(3)) and hydrogen sulfide (H(2)S) was assessed from the
      perspective of animal welfare and occupational hygiene. Summer data of H(2)S,
      NH(3) and CO(2) concentrations and of environmental parameters were collected
      from 31 farms. The indices of exposure for long-term exposures to NH3 suggest the
      lowest acceptability of exposure was observed on poultry farms. CO(2) had the
      highest dependence on production activity. For H(2)S, no differences were found
      based on farming activity. Both the stocking density and volume of air available
      affected the daily exposure and the index of exposure to CO(2). Significant
      differences were observed between hourly CO(2) concentrations, depending on the
      level of activity inside the building. A positive correlation was found between
      gas concentrations and temperature increase. All values of daily and short-term
      exposures were below exposure limit values, which suggests that exposure
      conditions were appropriate for workers' health during the measurement period.
      Analysis of the working hours and average hourly concentration of gases during
      the times of day, with presence of workers inside the farm buildings, revealed
      significant differences for CO(2).

PMID- 22462441
TI  - Microbial air contamination in indoor environment of a university library.
AB  - The present study was aimed at evaluating the number of bacteria and mould fungi
      in the indoor and outdoor environment of Torun University Library. The sampling
      sites were located in the rooms serving the functions typical of libraries (i.e.
      in the Main Reading Room, Current Periodicals Reading Room, Collections
      Conservation Laboratory, Old Prints Storeroom, in rooms serving other (non
      library) functions (i.e. main hall, cafeteria, and toilet) as well as outside the
      library building. The analyses reveal that the concentrations of bacterial as
      well as fungal aerosols estimated with the use of the impaction method ranged
      between 10(1)-10(3) CFU.m(-3), which corresponds to the concentrations normally
      observed in areas of this kind. Evaluation of the hygienic condition of the
      studied areas was based on the criteria for microbiological cleanliness in
      interiors submitted by the European Commission in 1993. According to this
      classification, the air was considered to be heavily or moderately contaminated
      with bacteria, while the air contamination with mould fungi was described as low
      or moderate. The air in the Old Prints Storeroom was considered the least
      contaminated with microbial aerosol.

PMID- 22462442
TI  - Two generation reproductive and developmental toxicity following subchronic
      exposure of pubescent male mice to di(2-ethylhexyl)phthalate.
AB  - Di-(2-ethylhexyl)phthalate (DEHP) is widely present in the human environment. 
      The study aimed at the investigation of potential genotoxic effects induced by
      subchronic exposure to DEHP in germ cells of male mice in the first period of
      puberty, and to check if the transmission of mutation to the next generation via
      the sperm is possible. 8-weeks exposure to 2,000 mg/kg and 8,000 mg/kg of DEHP
      diminished sperm count and quality, leading to a reduced percentage of pregnant
      females mated to exposed males. A slight increase in the frequency of prenatal
      deaths and dominant lethal mutations, as well as a significantly increased
      percentage of abnormal skeletons among the F1 offspring of males exposed to 8,000
      mg/kg of DEHP, were observed. Exposure of the fathers did not cause a delay in
      the postnatal development of the offspring, except for fur development in the
      group of 8,000 mg/kg of DEHP. Gametes of male offspring of exposed fathers showed
      reduced motility. The results may suggest that diminished spermaozoa quality
      induced by DEHP may be coincidental with mutations leading to intrauterine deaths
      and skeletal abnormalities in the offspring.

PMID- 22462443
TI  - Characterization of Polish feline B. henselae isolates by multiple-locus tandem
      repeat analysis and pulse-field gel electrophoresis.
AB  - Knowledge about molecular epidemiology of B. henselae is important for
      recognizing the geographical distribution of strains and identification of
      isolates virulent for humans. Eleven Polish feline B. henselae isolates were
      typed, using 2 different techniques: pulse-field gel electrophoresis (PFGE) and
      multiple-locus variable-number tandem repeat analysis (MLVA). PFGE analysis
      distinguished 6 different PFGE types, with subtypes within 3 of them, whereas 10
      MLVA types were assigned. Global diversity index (D.I.) for MLVA equaled 0.93.
      For 7 isolates, the results of MLVA confirmed cluster assignments based on PFGE.
      Both PFGE and MLVA results were in accordance with epidemiological data. Although
      PFGE has been previously demonstrated to be a suitable method for the
      differentiation of B. henselae isolates/strains, our results show the superiority
      of MLVA over PFGE with respect to higher discriminatory power, distinguishing
      genotypes I and II isolates, easier analysis of results, and possibility to
      compare the numerical data obtained by different laboratories. With MLVA, 7 new
      profiles were observed, compared to previous results from around the world;
      whereas 3 known profiles were previously described mainly in European B. henselae
      isolates. Our results confirm that some VNTR profiles can be used as specific
      geographical markers.

PMID- 22462444
TI  - Molecular evidence of Anaplasma phagocytophilum and Babesia microti co-infections
      in Ixodes ricinus ticks in central-eastern region of Poland.
AB  - The aim of the study was to elucidate the distribution of Anaplasma
      phagocytophilum and Babesia microti co-infection in Ixodes ricinus populations
      within the central-eastern region of Poland. The prevalence of analysed tick
      borne human pathogens in single and polymicrobial infections in I. ricinus ticks
      were analysed using the conventional and nested PCR techniques. A total number of
      1,123 questing tick individuals (291 females, 267 males and 565 nymphs) were
      collected at different ecosystems (municipal parks, suburban forests, and
      woodlands). In the presented study, 95 samples of ticks (8.5%) were infected with
      A.phagocytophilum, 3.1% (n=35) with B. microti, whereas the co-existence status
      of these human pathogens was detected in 1.8% (n=20) of all tested samples. It
      has been demonstrated that the prevalence of co-infection status was the highest
      among females of I. ricinus (11 samples, 3.8%), whereas the lowest within tested
      nymphs (5 samples, 0.9%). Ticks collected at city parks in Warsaw and suburban
      areas of this town characterized the highest prevalence of co-infections (3.3 and
      4.8%, respectively). Furthermore, it was established that co-infection rates of
      ticks inhabiting woodlands within Kampinos National Park and Nadbuzanski
      Landscape Park were similar and reached the levels of 1.4% (n=5) and 1.1% (n=4),
      respectively.

PMID- 22462445
TI  - Exposure to phenoxyacetic acid herbicides and predictors of exposure among
      spouses of farmers.
AB  - The purpose of the study was to assess the environmental exposure to 2 commonly
      used pesticides: 2-methyl-4- chlorophenoxyacetic acid (MCPA) and 2,4
      dichlorophenoxyacetic acid (2,4-D) among spouses of farmers, not directly
      involved in the process of spraying. Exposure to 63 sprayings 24 women in
      households from the rural area of the Lodz Voivodeship in Poland was assessed.
      The women were asked to collect 3 biological urine samples: in the morning before
      spraying (sample A), in the evening after spraying (sample B), and on the morning
      of the next day (sample C). The determination of pesticides in urine was
      performed by high performance liquid chromatography, coupled with tandem mass
      spectrometry and negative electrospray (LC-MS/MS-ESI-). In the case of both
      active ingredient, the number of urine samples with the level of pesticides above
      limit of detection (LOD) increased from 30% in samples A to 45% in samples B and
      C. The average levels of herbicides increased from sample A (2.8 ng/g creatinine)
      to sample B (6.0 ng/g creatinine). The mean value of the C sample was 4.0 ng/g
      creatinine. Similar results were obtained when the average was calculated for all
      measurements, including those below LOD. The outdoor activity of the women during
      spraying was statistically significant (p=0.023), a predictor of exposure in
      multivariate analyses. The presented study indicates that farmers' spouses might
      be exposed to pesticides, even if they do not take part in the spraying.

PMID- 22462446
TI  - Canine dirofilariosis under specific environmental conditions of the Eastern
      Slovak Lowland.
AB  - The aim of the present study was to collect data from Eastern Slovak Lowland,
      southern Slovakia, to assess risk of the spread of canine dirofilariosis. Climate
      and environmental conditions in the Eastern Slovak Lowland are ideally suitable
      for the occurrence of vector-borne diseases. In the past, an endemic locality of
      dangerous mosquito transmitted malaria was found in this area. Today, another
      zoonotic parasitic disease threatens--dirofilariosis. The results of the first
      detailed study revealed a 34.44% prevalence in dogs harbouring dirofilariae. D.
      repens was diagnosed in all infected specimen, with 2 individuals being co
      infected also with D. immitis.

PMID- 22462447
TI  - Recurrence of Stachybotrys chartarum during mycological and toxicological study
      of bioaerosols collected in a dairy cattle shed.
AB  - Agricultural occupations associated with animal breeding and the processing of
      animal materials in confinement systems could potentially lead to bioaerosol
      exposures. Moulds and mycotoxins could be constituents of bioaerosols and should
      be studied because of their possible involvement in respiratory diseases and
      cancers. In order to characterize the fungal contamination of the indoor air in a
      dairy barn, bioaerosols were collected during 20 days in a cattle farm located in
      Normandy (France). Mycobiota, mycotoxins and the mutagenicity of bioaerosols were
      studied. The toxigenic ability of Aspergillus flavus group and Aspergillus
      fumigatus isolates was also evaluated in vitro. The prevalent airborne moulds
      were from the following potentially toxigenic species: Aspergillus flavus group,
      Aspergillus fumigatus, Penicillium chrysogenum, Stachybotrys chartarum, and the
      allergenic species Ulocladium chartarum, Cladosporium cladosporioides. In
      comparison with harvesting, grain handling or broiler breeding, the
      concentrations of viable moulds were lower in the cattle shed. Seasonal
      variations in levels of several species were also observed. This study revealed
      that aflatoxins were detected in bioaerosols and, for the first time, showed that
      farmers are possibly exposed to Stachybotrys chartarum during routine barn work.
      Moreover, the finding of mutagenicity from bioaerosols needs further
      investigations on bioaerosol composition.

PMID- 22462448
TI  - Validation of direct plating of a stool sample as a method for Listeria
      monocytogenes detection.
AB  - The aim of current studies was to validate the direct plating of a stool sample
      for Listeria monocytogenes detection, using selective medium Palcam agar with
      Palcam selective supplement. Validation was performed using stool samples
      collected from healthy humans inoculated with Listeria sp. strains. Stool samples
      were frozen to determine the influence of freezing on method robustness. The
      presented research defines the Listeria monocytogenes limit of detection (LOD) as
      10(3) cfu/g of stools for fresh and frozen samples. Repeatability and
      reproducibility of the method has been confirmed using statistical methods. We
      show the effectiveness of direct plating of stool samples on Palcam agar with
      Palcam selective supplement collected for Listeria monocytogenes detection. This
      method could be useful for this pathogen detection in stool samples collected
      from patients with diarrhoea.

PMID- 22462449
TI  - Antibiotic resistance of Escherichia coli isolated from a poultry slaughterhouse.
AB  - The aim of the study was to investigate the antibiotic resistant E. coli strains
      isolated from bioaerosols and surface swabs in a slaughterhouse as a possible
      source of poultry meat contamination. The highest air coliforms contamination was
      during shackling, killing and evisceration of poultry. The strains showed
      resistance to ampicillin (89%), ceftiofur (62%) and cefquinome (22%), while
      resistance to ampicillin with sulbactam was only 6%. Resistance to streptomycin
      and gentamicin was detected in 43% vs. 14% isolates; to tetracycline 33%; to
      chloramphenicol and florfenicol in 10% vs. 18% isolates; to cotrimoxazol in 35%
      isolates; to enrofloxacin in 43% isolates. The higher MIC of ceftazidime (3.6 mg
      x l(-1)) and ceftriaxon (5.2 mg x l(-1)) revealed the presence of ESBLs in 43% of
      isolates. From 19 selected phenotypically ESBL positive strains, 16 consisted of
      CMY-2 genes, while CTX-M genes were not detected by PCR. Maldi tof analysis of
      selected E. coli showed a clear clonal relatedness of environmental strains from
      various withdrawals.

PMID- 22462450
TI  - Risk factors for the spread of parasitic zoonoses among dog owners and their
      families in rural areas.
AB  - INTRODUCTION: Close animal-human contacts are risky for people, especially in
      cases of any negligence towards proper veterinary care, deworming procedures, as
      well as human and dog hygiene. Among possible risks there are parasite zoonoses
      threats. MATERIAL AND METHODS: The study involved 176 dog owners from rural
      regions in Lublin province. The original Parasitic Zoonoses Transmission Risk
      Score (PZTRS) method was used to determine the risk for humans, a method based on
      the analysis of such criteria as animal-human coexistence conditions and dog
      hygiene, as well as dewormings negligence. The resulting score ranges from 0-8,
      where. '0' is a perfect score, '8' is the lowest and means high health risks for
      humans. RESULTS: Obtained PZTRS values were in the 1-6 range. Median as well as
      modal values were equal to 4, which means the presence of significant risk of
      parasitic zoonoses transmission to dog owners and members of their families.
      CONCLUSIONS: In Polish rural areas, negligence of dog owners' duties, including
      improper hygiene and dewormings, as well as risky conditions of human-dog
      coexistence, increase the potential risk of zoonotic parasite diseases spreading.
      Nowadays, veterinary practices and media have the important responsibility of
      educating dog owners about the potential risk of zoonotic parasites.

PMID- 22462451
TI  - Susceptibility of food-contaminating Penicillium genus fungi to some
      preservatives and disinfectants.
AB  - Microscopic fungi are able to contaminate and deteriorate various food products
      and can subsequently cause health problems. Long usage of the same preservatives
      and disinfectants against spoilage fungi may lead to the development of fungal
      resistance to those chemicals. The objective of this study was to investigate the
      susceptibility of 3 Penicillium genus fungi, isolated from foodstuffs, to organic
      acid preservatives and some disinfectants, taking into consideration 2 aspects of
      their development: spore germination and mycelial growth. Susceptibility of
      Penicillium spinulosum, P. expansum and P. verruculosum to the preservatives,
      namely benzoic acid, sodium lactate, potassium sorbate, as well as disinfectants
      such as Topax DD, Suma Bac D10, Biowash and F210 Hygisept, was investigated. The
      biocides were used at concentrations of 0.1, 1.0 and 10%. Of the preservatives,
      benzoic acid and potassium sorbate showed the best inhibition, both on spore
      germination and mycelial growth. Benzoic acid at a concentration of a 0.1%
      reduced spore germination by 33-55%, and mycelial growth by 54-97%, whereas at 1%
      the inhibition was 74-85% and 97-100%, respectively. The effect of the
      disinfectants at a concentration of 0.1% on spore germination was 25-84% and on
      colonial growth 68-97%, while at 1.0% the reduction in spore germination reached
      53-91% and the inhibition of growth 89-100%. In most cases, the same
      concentrations added to the media showed higher inhibitory effect on mycelial
      growth than on spore germination. It was noticed that the fungi responded rather
      unevenly towards the biocides, showing individual susceptibility.

PMID- 22462452
TI  - Volatile profiles and aflatoxin production by toxigenic and non-toxigenic
      isolates of Aspergillus flavus grown on sterile and non-sterile cracked corn.
AB  - Aspergillus flavus is a saprophytic fungus which can grow on corn and produce
      aflatoxins which render it unsafe for consumption as food and feed. In this
      study, aflatoxin and non-aflatoxin producing isolates of A. flavus were grown
      separately on wet (20% water added), sterile or non-sterile cracked corn. Wet and
      dry cracked corn controls were included as needed. Secondary metabolic volatiles
      were identified and aflatoxin concentrations determined over a 12-day period.
      Volatiles unique to the toxigenic A. flavus isolates were determined by
      comparison with volatiles produced by the respective corn controls and the non
      toxigenic A. flavus isolate. The number and identity of the volatiles produced by
      these A. flavus isolates varied by isolate, whether sterile or non-sterile corn
      was the substrate, and the sampling day. Overall, most of the volatiles were
      produced before day 8 after inoculation. Aflatoxin production was 10-fold lower
      on the sterile corn, compared to the non-sterile corn. Volatiles unique to the
      aflatoxin producing isolates were identified on both substrates after comparison
      with those produced by the non-aflatoxin producing isolate, as well as the corn
      control samples. Results indicate that several factors (substrate, fungal
      isolate, culture age) affect volatile and aflatoxin production by A. flavus.

PMID- 22462453
TI  - The viability and intestinal epithelial cell adhesion of probiotic strain
      combination--in vitro study.
AB  - To be effective, probiotic bacteria must exhibit a number of functional
      characteristics, including the resistance to gastric acidity and the ability to
      adhere to the intestinal epithelium. In this study, we examined in vitro the
      viability of lactic acid bacteria (LAB) combination after exposure to low pH, and
      the adhesion of LAB to Caco-2 cells during coincubation of 9 bacterial strains.
      To test bacterial viability, 6 commercially available products were incubated in
      0.1 N HCl at pH 1.2 for 60 min. The greatest growth inhibition was noted for the
      non-capsulated product containing the Lactobacillus rhamnosus strain (log
      reduction of CFU = 6.4), and the best survival observed for the product
      containing 9 bacterial strains, equipped with a modern capsule made according to
      the Multi-Resistant Encapsulation technology (log reduction of CFU = 0.1). In the
      adhesion experiment, the combination of 9 bacterial strains was added to 17-day
      old Caco-2 cell culture for 90 min. The greatest efficiency of adhesion was
      observed for the inoculum containing 5.5x10(8) CFU/mL/9.6 cm(2) of Caco-2 and the
      dose of probiotic bacteria of 190 cells per one Caco-2 cell. As a result,
      approximately 157 bacterial cells adhered to one Caco-2 cell. The results
      indicate that the combination of 9 bacterial strains in the examined product is
      characterized as highly adhesive.

PMID- 22462455
TI  - Physical activity of Polish adolescents and young adults according to IPAQ: a
      population based study.
AB  - The alarming problem of a decline in physical activity among children and
      adolescents and its detrimental effects on public health has been well recognised
      worldwide. Low physical activity is responsible for 6% of deaths worldwide and 5
      10% of deaths in the countries of the WHO European Region, according to country.
      Within the last decade, many initiatives have been launched to counteract this
      phenomenon. The objective of presented study was analysis of the level of
      physical activity among adolescents and young adults in Poland, according to the
      IPAQ questionnaire. The study group covered 7,716 adolescents: 5,086 children
      attending high school and secondary schools and 2,630 university students. Low
      physical activity was noted among 57% of schoolchildren and 20.84% of students.
      Analysis of the level of physical activity according to the IPAQ indicated that
      it was lower among girls, compared to boys. An additional analysis, with the
      consideration of the place of residence, showed that the highest percentage of
      the population with low physical activity was noted in the rural areas (29.30%),
      while among the urban inhabitants of cities with a population above 100,000 it
      was on the level of 23.69% and 20.57%. Median for weekly physical activity by
      respondents" gender was on the level of 1,554.00 MET*min. weekly among females,
      and 2,611.00 MET*min. weekly among males (p<0.000). The highest weekly physical
      activity expressed in MET*min. was observed among the inhabitants of towns with a
      population less than 100,000, whereas among the rural population and inhabitants
      of large cities with a population of over 100,000 the weekly physical activity
      was on a similar level (1,830.50 and 1,962.00 respectively). An extended analysis
      of respondents' physical activity showed that during the day students spend
      significantly more time in a sedentary position, compared to schoolchildren. The
      presented results of studies indicate the necessity to continue and intensify
      actions to promote various forms of physical activity among students and
      schoolchildren. A constant decrease in physical activity observed among children
      and adolescents suggests that it is necessary to pay greater attention to this
      social group while developing health programmes.

PMID- 22462454
TI  - Dietary behaviours of adolescents from urban and rural areas in the district of
      Szamotuly--a preliminary study.
AB  - INTRODUCTION: Numerous factors and conditions affect the dietary behaviours of
      the young population. Urban-rural differences may also influence the lifestyle of
      adolescents, including diet. AIM: To describe dietary behaviours of two young
      populations: living in urban or rural areas in the district of Szamotuly (a city
      with a population of 19,000 inhabitants). MATERIAL AND METHODS: 116 adolescents
      aged 15-17 years were included to this preliminary study and asked to answer
      questions concerning health and lifestyle. RESULTS: No statistically significant
      difference was detected in the number of meals eaten daily, and 3 meals a day was
      the most frequent answer (45.9% in the rural group and 32.7% in the urban group).
      About 41.0% of rural subjects and 50.9% of urban ones admitted that they ate
      fresh fruit and vegetables every day. There was no statistically significant
      difference in the medium consumption frequency of fresh fruit, vegetable, fish,
      sweets and salty snacks. CONCLUSIONS: 1. Between rural and urban adolescents no
      statistically significant differences were observed in dietary behaviours
      concerning medium number of meals eaten daily, medium frequency of fresh fruit
      and vegetable consumption, medium monthly frequency of fish consumption, medium
      weekly frequency of consumption of sweets and salty snacks. 2. More than a half
      of the young rural dwellers preferred more salty meals in contrast to over 56% of
      urban youths who preferred less salty meals. Both urban and rural adolescents
      most often declared that eat sweets and salty snacks daily. 3. There is a great
      need to change the dietary habits of teenagers, especially in avoiding an over
      intake of high fat and high energy products, in order to reduce the rising
      prevalence of obesity among adolescents.

PMID- 22462456
TI  - Tobacco-related Foetal Origin of Adult Diseases Hypothesis--population studies in
      Poland.
AB  - Epidemiological studies in Poland show that tobacco smoking by adolescents at
      reproductive age is still frequently observed. This concerns both boys and girls.
      The study was based on all-Polish population studies of health behaviours of
      adolescents aged 14-24 (Youth Behavioural Polish Survey--YBPS) conducted in 2011,
      and the Pregnancy-related Assessment Monitoring Survey (PrAMS). More than 12% of
      pregnant women do not discontinue smoking in association with becoming pregnant
      and expose the foetus to tobacco smoke, despite being aware of the hazardous
      effect of smoking on the health of the mother and child. Smoking in pregnancy is
      mainly observed among mothers with a low education level and those aged under 23.
      According to the Baker's Foetal Origins of Adult Health and Diseases Hypothesis,
      exposure of the foetus to the components of tobacco smoke results in many
      perturbations in the form of a lower birth weight, prematurity, worse state of
      neonates after birth, and higher susceptibility to contacting civilization
      diseases at the age of adulthood. The results of studies confirm some
      observations. Polish studies clearly confirmed a lower birth weight of babies
      delivered by mothers who smoke; however, earlier termination of pregnancy and
      worse status of neonates after birth were not observed. According to the Baker's
      hypothesis, a lower birth weight of babies delivered by smoking mothers during
      the further life cycle exposes the offspring to the risk of contracting
      civilization diseases. The efforts undertaken by public health authorities should
      be biased towards education of the population at reproductive age about the
      hazardous effect of smoking on the health of the foetus and the offspring born.
      Women at reproductive age should be encouraged to discontinue smoking in
      association with the planning of pregnancy and in pregnancy.

PMID- 22462457
TI  - Quality of life in peri- and post-menopausal Polish women living in Lublin
      Province--differences between urban and rural dwellers.
AB  - INTRODUCTION AND OBJECTIVE: The quality of life in peri- and post-menopausal
      women constitutes a serious public health problem. The aim of this observational
      cross-sectional study was to reveal the influence of the permanent domicile on
      the quality of life of women in peri- and post-menopausal period, and to
      establish the influence of employment as a full-time agricultural worker on the
      quality of life in these women. MATERIALS AND METHODS: The research was carried
      out by means of a survey using the postal questionnaire technique. Three
      standardized questionnaires: WHOQOL-BREF, Women's Health Questionnaire (WHQ) and
      SF-36 were used as research tools. An original questionnaire was also used. The
      study comprised a representative sample of the female population aged 45-65
      living in Lublin Province. The sample size was 2,143 women. RESULTS: The quality
      of the women's life was significantly affected by the place of permanent
      residence. The worst quality of life was found in permanent country dwellers.
      City and town inhabitants revealed a considerably higher level of quality of
      life. Permanent place of residence in the country was an independent predictor of
      a poorer quality of life. Employment as a full-time agricultural worker was an
      independent predictor of a worse quality of life in the SOM domain of WHQ, as
      well as RP, RF and RE domains of SF-36. On the other hand, employment as a full
      time agricultural worker was an independent predictor of a better quality of life
      in the SLE domain of WHQ, and psychological domain of WHOQFL-BREF. CONCLUSIONS:
      Awareness of the dependence is necessary in order to effectively plan health
      education and physical and social health promotion campaigns. Country dwellers
      need special attention in the process of undertaking any preventive or curative
      steps.

PMID- 22462458
TI  - Analysis of lifestyle of young adults in the rural and urban areas.
AB  - An unhealthy lifestyle among young people is a serious and often unnoticed
      problem. It seems that there are differences in the lifestyle of young people
      from rural and urban areas. The objective of this study was to compare eating
      habits and physical activity of young adults according to their body weight,
      gender and place of residence. The study involved a group of 18-year-olds from
      rural and urban environments. The study included 50% girls and 50% of boys in
      each group, selected by simple random sampling (SRS). The author-designed
      questionnaire evaluating the nutrition habits and physical activity was provided.
      It was found that in the group of boys the value of BMI was markedly higher than
      in girls. Compared to the normal weight, young overweight adults ate meals more
      frequency, the majority preferred meat dishes, more often ate under the stress,
      and had lower physical activity. It was found that gender had a significant
      impact on the studied parameters. The girls ate meals more frequent during the
      day, the majority preferred fruit and vegetable, but had lower physical activity
      than the boys. It was found that the young adults from the rural area preferred
      fast food and frequently ate sweets. Compared to the subjects from the urban
      environment, the young adults living in the countryside consumed fewer meals
      daily and were more physical active. About a half of the studied adults were not
      satisfied with their weight, and nearly 40% of the subjects in both groups
      admitted that they had made effective or ineffective attempts to lose weight. The
      lifestyles of young people in rural and urban areas were slightly different;
      however, dietary factors which predispose to weight gain were comparable in both
      groups. In the rural areas, the most frequent nutritional faults were a
      preference for fast food, frequent consumption of sweets, and few meals during
      the day. A positive aspect of the lifestyle of young people in the rural areas
      was a relatively high level of physical activity and the small effect of stress
      on excessive consumption.

PMID- 22462459
TI  - Social and family-related correlates of medical care utilization by asthmatic
      children in Upper Silesia, Poland.
AB  - BACKGROUND: Studies on childhood asthma demonstrate socioeconomic disparities in
      medical care utilization. A lack of information for Poland prompted our
      investigation into this question. Its goal was to discover if the utilization of
      medical services by asthmatic children depends on social and family factors.
      METHODS: Subjects were 186 children with physician-diagnosed asthma, identified
      through a questionnaire survey of 4,535 school children in Katowice District,
      Poland. Utilization of medical care was assessed by such past year events as
      medical visits (44.0%), any diagnostic test (35.4%) and spirometry (30.6%).
      Association of those events with socioeconomic variables was explored by means of
      logistic regression, according to the criterion p< 0.1. RESULTS: After adjustment
      for disease severity and gender medical visits were related to younger age
      (p=0.009), family history of respiratory diseases (p=0.08) and rural residence
      (p=0.09), any diagnostic tests to younger age (p=0.08), smaller number of
      siblings (p=0.01) and rural residence (p=0.004); spirometry to smaller number of
      siblings (p=0.09) and rural residence (p=0.006). CONCLUSION: Clinical status and
      age are important determinants of utilization of medical services by asthmatic
      children. The effects of rural residence and family size may reflect a more
      attentive response to the needs of a sick child.

PMID- 22462460
TI  - Utilization of non-medical healing methods as a way of coping with life
      difficulties in the socially deprived 'losers' of the systemic transformation
      processes in Poland.
AB  - INTRODUCTION AND OBJECTIVES: One of the features of systemic transformation are
      its social costs. This is also the case with the Polish transformation initiated
      in 1989. Social processes connected with it are a kind of accelerator which
      increases the range of health needs realized outside the medical system.
      Utilization of non-medical healing methods may also be perceived as a way of
      coping with negative, i.e. sociopsychological consequences of transformation,
      including the fact that many people's health needs were not met within
      institutional medicine. Such a situation results in a deepening of social
      inequalities in health. This problem will be presented from the perspective of
      'ordinary people' in accordance with the leading research directive in medical
      sociology. Following the directives of humanistic sociology, the sources of
      information on the subject were personal documents. MATERIALS AND METHODS: The
      paper presents selected results of the sociological qualitative analysis of 1,311
      letters received by the editorial section of public Polish Television's Channel
      Two in 1991 in connection with the broadcasting of a series of programmes
      conducted by the unconventional therapist Anatoly M. Kashpirovsky, who had a
      viewership of eight to nine million, on average. The presented and commented-on
      material consists of spectators' statements on the adverse consequences of the
      systemic transformation, concerning health and illness. RESULTS: The post-1989
      political-system transformation is the most thorough-going social change in post
      war Poland. It triggered off a number of both positive and negative processes.
      The negative ones include the deepening of social inequalities in health as a
      result of, inter alia, the progressive pauperization of society and also the
      growing utilization of non-medical healing methods. The negative effects of
      transformations are especially felt by typical 'clients' of Anatoly M.
      Kashpirovsky: poorly educated, indigent, residents of villages and small Polish
      towns: 'the transformation process losers'. CONCLUSIONS: Systematic sociological
      knowledge on the ways of description and interpretation of health and illness by
      'lay people' enables a more complete understanding of phenomena related to
      inequalities in health, including their social and structural causes.

PMID- 22462461
TI  - Parallel reduction in expression of the eye development gene hedgehog in
      separately derived cave populations of the amphipod Gammarus minus.
AB  - Caves provide excellent settings to examine evolutionary questions. Subterranean
      environments are characterized by similar and consistent conditions. Cave-adapted
      species often share characteristics such as diminished pigmentation, elongated
      limbs and reduced or absent eyes. Relatively little is known about the evolution
      and development of troglomorphic traits in invertebrates. In this study, we
      compare expression of the eye development genes hedgehog, pax6, sine oculis and
      dachshund in individuals from multiple independently derived cave populations of
      the amphipod Gammarus minus. hedgehog expression was significantly reduced in
      cave populations, compared to genetically related surface populations.
      Interestingly, no differences were found in pax6, sine oculis or dachshund
      expression. Because hedgehog-related genes are also involved in eye reduced in
      Astyanax mexicanus, these genes may be consistent targets of evolution during
      cave adaptation. These results provide support for the hypothesis of genomic
      'hotspots' of evolution and allow comparison of adaptive mechanisms among diverse
      animals in subterranean environments.

PMID- 22462462
TI  - How can we maximize nursing students' learning about research evidence and
      utilization in undergraduate, preregistration programmes? A discussion paper.
AB  - AIM: This article presents a discussion on how to maximize nursing students'
      learning about research for evidence-based practice in undergraduate,
      preregistration programmes. BACKGROUND: Evidence-based practice may use
      information from many sources, including research. Research utilization concerns
      the translation of research findings into practice. Thus, while evidence-base
      practice may not be solely research-based and hence more than research
      utilization, research remains an important ingredient in ensuring quality and
      cost-effective care and an academic requirement for nursing students undertaking
      a science degree-level qualification. Nevertheless, how educators can best
      support research-related learning and application remains uncertain and requires
      discussion. DATA SOURCES: MEDLINE, CINAHL, Social Science Citation Index, British
      Nursing Index, and Intute were searched for papers published 1980-2011 using the
      following search terms: research, research utilization, evidence-based practice,
      learning, teaching, education, training, nursing, health, and social care.
      DISCUSSION: Nursing students need to be able to value the relevance, authority,
      and utility of nursing research for patient care through embedding research
      learning in both academic and practice-based settings. Students can be supported
      in learning how to access, understand, and appraise the authority of research
      through weaving these skills into enquiry-based learning. Furthermore,
      encouraging students to undertake research-based practice change projects can
      support research utilization and development skills. CONCLUSION: Research should
      be fully embedded throughout nursing curricula beyond the confines of 'research
      classes', integrating learning in academic and practice-based settings. Although
      this requires synergistic and integrated support of student learning by nurse
      educators, managers, clinical practitioners, researchers and policymakers; nurse
      educators have a pivotal role.

PMID- 22462463
TI  - Thermodynamics of antimicrobial peptide JCpep8 binding to living Staphylococcus
      aureus as a pseudo-stationary phase in capillary electrochromatography and
      consequences for antimicrobial activity.
AB  - To understand the details of the permeation pathways of antimicrobial peptide
      JCpep8, the antimicrobial processes were investigated step by step in this paper.
      First, the characterization of the initial binding process was explored by
      introducing the living Staphylococcus aureus cells (LSACs) into electrophoretic
      buffer used as pseudo-stationary phase in capillary electrochromatography (CEC),
      and the thermodynamic parameters were determined. The binding constants at 298,
      303, and 309 K were 7.40 * 1011, 1.43 * 1012, and 2.6 * 1012 M-1, respectively,
      which indicated the evident interaction between JCpep8 and LSACs. This binding
      process was spontaneous. Both the electrostatic force and hydrophobic effect play
      major roles in this binding process. Second, antibacterial activity kinetics and
      outer membrane and inner membrane disruption assays were investigated. Data
      indicated that JCpep8 killed microbes principally by breaking their cell wall and
      membrane, followed by cell lysis. The results were confirmed by Fourier transform
      infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). In
      summary, JCpep8 kills microbes mainly by wall-/membrane-targeting pore-forming
      mechanisms.

PMID- 22462464
TI  - Effect of large incisor retraction on upper airway morphology in adult
      bimaxillary protrusion patients.
AB  - OBJECTIVE: To evaluate, using multislice computed tomography (MSCT), the
      morphologic changes in the upper airway after large incisor retraction in adult
      bimaxillary protrusion patients. MATERIALS AND METHODS: Thirty adult patients
      with bimaxillary protrusion had four first premolars extracted, and then
      miniscrews were placed to provide anchorage. A CT scan was performed before
      incisor retraction and again posttreatment. Three-dimensional (3D) reconstruction
      of the pre- (T1) and post- (T2) CT data was used to assess for morphological
      changes of the upper airway. A paired t-test was used to compare changes from T1
      to T2. The relationship among the three variables (upper incisor retraction
      amount, upper airway size, and hyoid position) was analyzed by Pearson
      correlation coefficient. RESULTS: The amounts of upper incisor retraction at the
      incisal edge and apex were 7.64 +/- 1.68 mm and 3.91 +/- 2.10 mm, respectively.
      The hyoid was retracted 2.96 +/- 0.54 mm and 9.87 +/- 2.92 mm, respectively, in
      the horizontal and vertical directions. No significant difference was observed in
      the mean cross-sectional area of the nasopharynx (P > .05) between T1 and T2,
      while significant differences between T1 and T2 were found in the mean cross
      sectional areas of the palatopharynx, glossopharynx, and hypopharynx (P < .05);
      these mean cross-sectional areas were decreased by 21.02% +/- 7.89%, 25.18% +/-
      13.51%, and 38.19% +/- 5.51%, respectively. The largest change in the cross
      sectional area is always noted in the hypopharynx. There was a significant
      correlation among the retraction distance of the upper incisor at its edge, the
      retraction distance of the hyoid in the horizontal direction, and the decrease of
      the hypopharynx. CONCLUSION: Large incisor retraction leads to narrowing of the
      upper airway in adult bimaxillary protrusion patients.

PMID- 22462465
TI  - Outcome of retinal reattachment surgery in dogs: a retrospective study of 145
      cases.
AB  - OBJECTIVE: To summarize the clinical outcomes and complications of pars plana
      vitrectomy with perfluoro-n-octane (PFO)-silicone oil exchange and endolaser
      retinopexy for treatment of retinal detachment (RD) in dogs, at one surgical
      center. PROCEDURE: Records of 145 dogs (168 eyes) that underwent retinal
      reattachment surgery (RR) between 2005 and 2009 were reviewed. All surgeries were
      performed by the same surgeon (SS). Data collected from the medical records
      included signalment, duration of time from diagnosis of RD to surgical
      intervention, if prior lensectomy was performed, time from surgery to restoration
      of vision, and postoperative complications. The data was analyzed to test the
      effect of breed, prior lensectomy, and time from diagnosis to surgery on visual
      outcome, tendency for complications, and time of complication onset. RESULTS: One
      hundred thirty pure-bred dogs (36 breeds) and 15 mixed-breed dogs were
      represented. One hundred fifty-five of 168 eyes (92%) were visual after surgery.
      Six of 155 eyes (3.8%) were visual before the procedure and retained vision; one
      hundred forty-nine of 155 eyes (96%) were nonvisual before and regained vision
      afterward. Thirteen of 168 eyes (8%) that were nonvisual prior to the procedure
      did not regain vision. The most common complications in order of occurrence
      included: cataract development, silicone prolapse into the anterior chamber,
      corneal ulceration, retinal degeneration, glaucoma, and uveitis. CONCLUSIONS:
      Pars plana vitrectomy with PFO-silicone oil exchange and endolaser retinopexy for
      treatment of RD in dogs is highly successful and associated with overall good
      visual outcome.

PMID- 22462466
TI  - Ethnic inequalities in mental health status and care: unravelling the
      determinants and consequences. Editors' foreword.

PMID- 22462467
TI  - The complexity of explaining ethnic differences in suicide and suicidal
      behaviours.

PMID- 22462468
TI  - Suicide studies in ethnic minorities: improving the science to help develop
      policy.

PMID- 22462469
TI  - Parity of esteem as a guiding principle for commissioning, service provision and
      laws related to health care: what do we know.

PMID- 22462470
TI  - A biotechnological T-shirt monitors the patient's heart during hemodialysis.
AB  - Uremic patients are characterized by a "pro-arrhythmic substrate." Arrhythmia
      appearance during hemodialysis (HD) is an unexpected event with a high incidence
      of mortality and morbidity and difficult to record in patients repeatedly checked
      using electrocardiogram (ECG). Furthermore the carrying out of this important
      examination by classical devices during HD is uncomfortable and sometimes
      stressful for the patient. It may be very useful to monitor the patient's cardiac
      activity during the whole HD session. We tried to overcome these difficulties
      using Whealthy((r)) (Wearable Health Care System), a wearable system in a T-shirt
      composed of conductors and piezoresistive materials, integrated to form fibers
      and threads connected to tissular sensors, electrodes, and connectors. ECG and
      pneumographic impedance signals are acquired by the electrodes in the tissue, and
      the data are registered by a small computer and transmitted via GPRS or
      Bluetooth.

PMID- 22462471
TI  - The success rate of immediate implant placement of mandibular molars: a clinical
      and radiographic retrospective evaluation between 2 and 8 years.
AB  - BACKGROUND: Dental implants, indicated for re-establishing both mastigatory and
      aesthetic functions, can be placed in the sockets immediately after tooth
      extraction. Most studies investigate the anterior and upper regions of the dental
      arch, whereas few examine longitudinal appraisal of immediate implant
      installation in the mandibular molar region. OBJECTIVE: The aim of this
      retrospective study was to evaluate the success rate of immediate dental implants
      placement in mandibular molars within a follow-up period as long as 8 years.
      MATERIALS AND METHODS: Seventy-four mandibular molar implants after non-traumatic
      tooth extraction between 2002 and 2008 were examined in the study. All implants
      were evaluated radiographically immediately after prosthesis placement, 1 year
      after implantation, and by the end of the experimental period, in 2010. Clinical
      evaluation was done according to [Albrektsson et al. (1986) The International
      Journal of Oral & Maxillofacial Implants, 1, 11-25] success criteria for marginal
      bone loss. The mean bone losses, calculated as the difference between the final
      evaluation measures and those taken by the end of the first year of implant, were
      compared using Kruskal-Wallis test with a significance level of 5%. RESULTS: All
      implants presented clinical and radiographic stable conditions, that is, 100%
      success rate. Significant bone loss was not found between final evaluation and
      that of the first functional year (P > 0.05). CONCLUSION: Immediate implant
      placement of mandibular molars proved to be a viable surgical treatment given the
      high success rate up to 8 years after implantation.

PMID- 22462472
TI  - Composition and dynamics of biostimulated indigenous oil-degrading microbial
      consortia from the Irish, North and Mediterranean Seas: a mesocosm study.
AB  - Diversity of indigenous microbial consortia and natural occurrence of obligate
      hydrocarbon-degrading bacteria (OHCB) are of central importance for efficient
      bioremediation techniques. To investigate the microbial population dynamics and
      composition of oil-degrading consortia, we have established a series of identical
      oil-degrading mesocosms at three different locations, Bangor (Menai Straits,
      Irish Sea), Helgoland (North Sea) and Messina (Messina Straits, Mediterranean
      Sea). Changes in microbial community composition in response to oil spiking,
      nutrient amendment and filtration were assessed by ARISA and DGGE fingerprinting
      and 16Sr RNA gene library analysis. Bacterial and protozoan cell numbers were
      quantified by fluorescence microscopy. Very similar microbial population sizes
      and dynamics, together with key oil-degrading microorganisms, for example,
      Alcanivorax borkumensis, were observed at all three sites; however, the
      composition of microbial communities was largely site specific and included
      variability in relative abundance of OHCB. Reduction in protozoan grazing had
      little effect on prokaryotic cell numbers but did lead to a decrease in the
      percentage of A. borkumensis 16S rRNA genes detected in clone libraries. These
      results underline the complexity of marine oil-degrading microbial communities
      and cast further doubt on the feasibility of bioaugmentation practices for use in
      a broad range of geographical locations.

PMID- 22462473
TI  - Azo anion radical complex of rhodium as a molecular memory switching device:
      isolation, characterization, and evaluation of current-voltage characteristics.
AB  - Two rare examples of azo anion diradical complexes of Rh(III) are reported. These
      complexes showed excellent memory switching properties with a large ON/OFF ratio
      and are suitable for RAM/ROM applications. Their electronic structures have been
      elucidated using a host of physical methods, including X-ray crystallography,
      variable-temperature magnetic susceptibility measurement, cyclic voltammetry,
      electron paramagnetic resonance spectroscopy, and density functional theory. The
      results indicate a predominant triplet state description of the systems with two
      ferromagnetically coupled radicals.

PMID- 22462475
TI  - Control of intramolecular pi-pi stacking interaction in cationic iridium
      complexes via fluorination of pendant phenyl rings.
AB  - Intramolecular pi-pi stacking interaction in one kind of phosphorescent cationic
      iridium complexes has been controlled through fluorination of the pendant phenyl
      rings on the ancillary ligands. Two blue-green-emitting cationic iridium
      complexes, [Ir(ppy)(2)(F2phpzpy)]PF(6) (2) and [Ir(ppy)(2)(F5phpzpy)]PF(6) (3),
      with the pendant phenyl rings on the ancillary ligands substituted with two and
      five fluorine atoms, respectively, have been synthesized and compared to the
      parent complex, [Ir(ppy)(2)(phpzpy)]PF(6) (1). Here Hppy is 2-phenylpyridine,
      F2phpzpy is 2-(1-(3,5-difluorophenyl)-1H-pyrazol-3-yl)pyridine, F5phpzpy is 2-(1
      pentafluorophenyl-1H-pyrazol-3-yl)-pyridine, and phpzpy is 2-(1-phenyl-1H-pyrazol
      3-yl)pyridine. Single crystal structures reveal that the pendant phenyl rings on
      the ancillary ligands stack to the phenyl rings of the ppy ligands, with dihedral
      angles of 21 degrees , 18 degrees , and 5.0 degrees  between least-squares planes
      for complexes 1, 2, and 3, respectively, and centroid-centroid distances of 3.75,
      3.65, and 3.52 A for complexes 1, 2, and 3, respectively, indicating
      progressively reinforced intramolecular pi-pi stacking interactions from
      complexes 1 to 2 and 3. Compared to complex 1, complex 3 with a significantly
      reinforced intramolecular face-to-face pi-pi stacking interaction exhibits a
      significantly enhanced (by 1 order of magnitude) photoluminescent efficiency in
      solution. Theoretical calculations reveal that in complex 3 it is unfavorable in
      energy for the pentafluorophenyl ring to swing by a large degree and the
      intramolecular pi-pi stacking interaction remains on the lowest triplet state.

PMID- 22462474
TI  - 5-HT(1B)  receptors inhibit glutamate release from primary afferent terminals in
      rat medullary dorsal horn neurons.
AB  - BACKGROUND AND PURPOSE: Although 5-HT(1B) receptors are expressed in trigeminal
      sensory neurons, it is still not known whether these receptors can modulate
      nociceptive transmission from primary afferents onto medullary dorsal horn
      neurons. EXPERIMENTAL APPROACH: Primary afferent-evoked EPSCs were recorded from
      medullary dorsal horn neurons of rat horizontal brain stem slices using a
      conventional whole-cell patch clamp technique under a voltage-clamp condition.
      KEY RESULTS: CP93129, a selective 5-HT(1B) receptor agonist, reversibly and
      concentration-dependently decreased the amplitude of glutamatergic EPSCs and
      increased the paired-pulse ratio. In addition, CP93129 reduced the frequency of
      spontaneous miniature EPSCs without affecting the current amplitude. The CP93129
      induced inhibition of EPSCs was significantly occluded by GR55562, a 5-HT(1B/1D)
      receptor antagonist, but not LY310762, a 5-HT(1D) receptor antagonist.
      Sumatriptan, an anti-migraine drug, also decreased EPSC amplitude, and this
      effect was partially blocked by either GR55562 or LY310762. On the other hand,
      primary afferent-evoked EPSCs were mediated by the Ca(2+) influx passing through
      both presynaptic N-type and P/Q-type Ca(2+) channels. The CP93129-induced
      inhibition of EPSCs was significantly occluded by omega-conotoxin GVIA, an N-type
      Ca(2+) channel blocker. CONCLUSIONS AND IMPLICATIONS: The present results suggest
      that the activation of presynaptic 5-HT(1B) receptors reduces glutamate release
      from primary afferent terminals onto medullary dorsal horn neurons, and that 5
      HT(1B) receptors could be, at the very least, a potential target for the
      treatment of pain from orofacial tissues.

PMID- 22462476
TI  - Single-Crystal Raman Evidence for and X-Ray Analysis of the Distorted Square
      Pyramidal Pentachlorothallate and Pentachloroindate Complexes in
      [(C(2)H(5))(4)N](2)[TlCl(5)] and [(C(2)H(5))(4)N](2)[InCl(5)].

PMID- 22462477
TI  - Nonlinear signal response in electrospray mass spectrometry: implications for
      quantitation of arsenobetaine using stable isotope labeling by liquid
      chromatography and electrospray Orbitrap mass spectrometry.
AB  - Isotope amount ratio measurements by electrospray ionization mass spectrometry
      show large systematic biases. Moreover, the signal ratio response can vary
      nonlinearly with respect to the amount ratio depending on the concentration of
      the analyte or coeluting matrix components, among other things. Since isotope
      dilution relies inherently on the linearity of response, accurate quantitation is
      then more difficult to achieve. In this study, we outline a method to eliminate
      the quantitation errors due to the effects of the nonlinear signal response. The
      proposed approach is a hybrid of the method of standard additions and isotope
      dilution allowing correction for nonlinear trend. As a proof of concept,
      determination of arsenobetaine content in fish tissue was performed using liquid
      chromatography coupled with a linear quadrupole ion trap (LTQ) Orbitrap mass
      spectrometer. The nonlinear isotope dilution method could, in principle, be
      applied to correct isotope ratio measurement biases in popular relative
      quantitation methods of biomolecules such as stable isotope labeling by amino
      acids in cell culture (SILAC), isotope-coded affinity tag (ICAT), or isobaric
      tags for relative and absolute quantification (iTRAQ).

PMID- 22462478
TI  - Vanadium isotopic composition of the sea squirt (Ciona savignyi).
AB  - Vanadium (V) in the sea squirt (Ciona savignyi) from Onagawa Bay, Miyagi, Japan,
      was isolated and purified through adsorption on a diamine resin and anion and
      cation exchanges after the dissolution of sea squirt samples with nitric acid and
      hydrogen peroxide. The (50)V/(51)V isotope ratio of V thus obtained was mass
      spectrometrically determined to be from 2.51*10(-3) to 2.55*10(-3) with the
      average of 2.53*10(-3) by the thermal ionisation technique. This value agreed
      with those of vanadyl chloride and vanadyl nitrate both prepared from vanadyl
      sulphate (Wako Pure Chemical Industries, Ltd., Japan) and of V in coastal
      seawater (Shimokita Peninsula, Aomori, Japan) within experimental uncertainties
      (standard deviation of+/-0.04), which suggested that no appreciable V isotope
      fractionation occurs accompanying V uptake by the sea squirt from sea water.

PMID- 22462480
TI  - Intra-arterial thrombolysis as an ideal treatment for inflammatory bowel disease
      related thromboembolic stroke: a case report and review.
AB  - Thromboembolism, both venous and arterial, is a well-known complication of
      inflammatory bowel disease, with the risk of stroke highest when patients are
      less than 50 years of age. Because inflammatory bowel disease patients often have
      gastrointestinal bleeding, it is a challenge to treat their thromboembolic events
      with systemic therapy. In this case, a 42-year-old woman with Crohn's disease
      developed a thromboembolism in her middle cerebral artery and was successfully
      treated with local intra-arterial thrombolysis. There is a growing trend to treat
      thromboembolic events in inflammatory bowel disease patients with local
      thrombolysis as it leads to better outcomes with regards to both the resolution
      of the thromboembolism and decreased secondary gastrointestinal bleeding.

PMID- 22462481
TI  - Correlates to the variable effects of cannabis in young adults: a preliminary
      study.
AB  - BACKGROUND: Cannabis use can frequently have adverse affects in those that use it
      and these can be amplified by various characteristics of an individual, from
      demographic and environmental variations to familial predisposition for mental
      illnesses. METHODS: The current study of 100 individuals, who were cannabis users
      during their adolescence and may still be users, was a survey of the self
      perceived effects of cannabis and their correlates. A reliable family member was
      also interviewed for determination of family history of various major mental
      illnesses and substance use. RESULTS: As many as 40% of cannabis users had
      paranoid feelings (suspiciousness) when using cannabis, although the most
      frequent effect was feeling relaxed (46%). Having a familial background for
      mental illnesses such as depression or schizophrenia did not determine the
      effects of cannabis nor its pattern of use, although the number of subjects with
      such a history was small. An age at which an individual began using cannabis did
      have an effect on how heavily it was used and the heavier the cannabis use, the
      more likely the individual was also to have had psychotic symptoms after use.
      There were no sex differences in effects of cannabis. These results are tempered
      by the reliance on self-report for many of the variables ascertained. CONCLUSION:
      Cannabis can frequently have negative effects in its users, which can be
      amplified by certain demographic and/or psychosocial factors. Thus, users with a
      specific profile may be at a higher risk of unpleasant effects from cannabis use
      and caution should be noted when cannabis is administered to young people for
      medicinal purposes.

PMID- 22462482
TI  - Synthesis of pH-responsive particles with shape anisotropy.
AB  - Seeded emulsion polymerization is used to produce large quantities of shape
      anisotropic, amphoteric particles in a size range of about 1 MUm. Copolymer
      dicolloids (CDCs) containing pyridine groups are synthesized by swelling
      spherical, lightly cross-linked polystyrene seeds with a mixture of styrene and
      pH-responsive monomer 2-vinyl pyridine followed by secondary polymerization to
      contrast with their analogue homopolymer dicolloids (HDCs) where the swelling
      step is carried out with styrene alone. After the particles are coated with a
      nonionic surfactant to minimize van der Waals attractions, surface potentials and
      aggregation properties of dilute suspensions are studied as functions of pH and
      ionic strength. Compared to HDCs, which remain stable at all pH values studied (3
      < pH < 9) up to an ionic strength of 5 M, the CDC particles show amphoteric
      behavior with strong attractions under conditions where dipolar interactions are
      expected to dominate.

PMID- 22462479
TI  - Endogenously released ACh and exogenous nicotine differentially facilitate long
      term potentiation induction in the hippocampal CA1 region of mice.
AB  - We examined the role of alpha7- and beta2-containing nicotinic acetylcholine
      receptors (nAChRs) in the induction of long-term potentiation (LTP). Theta-burst
      stimulation (TBS), mimicking the brain's naturally occurring theta rhythm,
      induced robust LTP in hippocampal slices from alpha7 and beta2 knockout mice.
      This suggests TBS is capable of inducing LTP without activation of alpha7- or
      beta2-containing nAChRs. However, when weak TBS was applied, the modulatory
      effects of nicotinic receptors on LTP induction became visible. We showed that
      during weak TBS, activation of alpha7 nAChRs occurs by the release of ACh,
      contributing to LTP induction. Additionally, bath-application of nicotine
      activated beta2-containing nAChRs to promote LTP induction. Despite predicted
      nicotine-induced desensitization, synaptically mediated activation of alpha7
      nAChRs still occurs in the presence of nicotine and contributed to LTP induction.
      Optical recording of single-stimulation-evoked excitatory activity with a voltage
      sensitive dye revealed enhanced excitatory activity in the presence of nicotine.
      This effect of nicotine was robust during high-frequency stimulation, and was
      accompanied by enhanced burst excitatory postsynaptic potentials. Nicotine
      induced enhancement of excitatory activity was observed in slices from alpha7
      knockout mice, but was absent in beta2 knockout mice. These results suggest that
      the nicotine-induced enhancement of excitatory activity is mediated by beta2
      containing nAChRs, and is related to the nicotine-induced facilitation of LTP
      induction. Thus, our study demonstrates that the activation of alpha7- and beta2
      containing nAChRs differentially facilitates LTP induction via endogenously
      released ACh and exogenous nicotine, respectively, in the hippocampal CA1 region
      of mice.

PMID- 22462483
TI  - Highly efficient asymmetric Mannich reaction of dialkyl alpha
      diazomethylphosphonates with N-carbamoyl imines catalyzed by chiral Bronsted
      acids.
AB  - An efficient method involving the first use of chiral phosphoric acids as
      catalysts in the asymmetric Mannich reaction of dialkyl diazomethylphosphonates
      and N-carbamoyl imines is developed. With only 0.1 mol % catalyst 1f, the
      reaction proceeded smoothly and produced the corresponding beta-amino-alpha
      diazophosphonate with up to 97% yield and >99% ee.

PMID- 22462485
TI  - The contribution of staff call light response time to fall and injurious fall
      rates: an exploratory study in four US hospitals using archived hospital data.
AB  - BACKGROUND: Fall prevention programs for hospitalized patients have had limited
      success, and the effect of programs on decreasing total falls and fall-related
      injuries is still inconclusive. This exploratory multi-hospital study examined
      the unique contribution of call light response time to predicting total fall
      rates and injurious fall rates in inpatient acute care settings. The conceptual
      model was based on Donabedian's framework of structure, process, and health-care
      outcomes. The covariates included the hospital, unit type, total nursing hours
      per patient-day (HPPDs), percentage of the total nursing HPPDs supplied by
      registered nurses, percentage of patients aged 65 years or older, average case
      mix index, percentage of patients with altered mental status, percentage of
      patients with hearing problems, and call light use rate per patient-day. METHODS:
      We analyzed data from 28 units from 4 Michigan hospitals, using archived data and
      chart reviews from January 2004 to May 2009. The patient care unit-month, defined
      as data aggregated by month for each patient care unit, was the unit of analysis
      (N = 1063). Hierarchical multiple regression analyses were used. RESULTS: Faster
      call light response time was associated with lower total fall and injurious fall
      rates. Units with a higher call light use rate had lower total fall and injurious
      fall rates. A higher percentage of productive nursing hours provided by
      registered nurses was associated with lower total fall and injurious fall rates.
      A higher percentage of patients with altered mental status was associated with a
      higher total fall rate but not a higher injurious fall rate. Units with a higher
      percentage of patients aged 65 years or older had lower injurious fall rates.
      CONCLUSIONS: Faster call light response time appeared to contribute to lower
      total fall and injurious fall rates, after controlling for the covariates. For
      practical relevance, hospital and nursing executives should consider strategizing
      fall and injurious fall prevention efforts by aiming for a decrease in staff
      response time to call lights. Monitoring call light response time on a regular
      basis is recommended and could be incorporated into evidence-based practice
      guidelines for fall prevention.

PMID- 22462486
TI  - Liver transplantation in a child with liver failure due to chronic graft-versus
      host disease after allogeneic hematopoietic stem cell transplantation from the
      same unrelated living donor.
AB  - We report a case of a six-yr-old boy who developed chronic GVHD of the liver,
      intestines, and skin following allogeneic hematopoietic SCT. The boy received an
      allogeneic hematopoietic stem cell transplant at the age of two yr because of
      early recurrence of ALL. Chimerism analysis showed complete chimerism. In the
      following year, he developed GVHD despite adequate immunosuppressive therapy.
      Liver biopsy showed liver GVHD resulting in liver cirrhosis by the age of five
      yr. LTx was performed with a left liver lobe from the unrelated donor from whom
      the stem cells had been taken. Immunosuppressive therapy consisted of low-dose
      steroids and low-dose cyclosporine. The postoperative course was uneventful.
      Graft function was excellent, and we performed protocol biopsies at seven days
      and three wk as well as three, six, and nine months after transplantation; none
      of these showed any signs of rejection or GVHD. Immunosuppressive therapy was
      discontinued nine months after LTx. Three yr after transplantation, the boy is in
      good condition with normal graft function. To our knowledge, this is the first
      report on LTx following allogeneic hematopoietic SCT from the same unrelated
      living donor.

PMID- 22462487
TI  - Improving resolution of public health surveillance for human Salmonella enterica
      serovar Typhimurium infection: 3 years of prospective multiple-locus variable
      number tandem-repeat analysis (MLVA).
AB  - BACKGROUND: Prospective typing of Salmonella enterica serovar Typhimurium (STM)
      by multiple-locus variable-number tandem-repeat analysis (MLVA) can assist in
      identifying clusters of STM cases that might otherwise have gone unrecognised, as
      well as sources of sporadic and outbreak cases. This paper describes the dynamics
      of human STM infection in a prospective study of STM MLVA typing for public
      health surveillance. METHODS: During a three-year period between August 2007 and
      September 2010 all confirmed STM isolates were fingerprinted using MLVA as part
      of the New South Wales (NSW) state public health surveillance program. RESULTS: A
      total of 4,920 STM isolates were typed and a subset of 4,377 human isolates was
      included in the analysis. The STM spectrum was dominated by a small number of
      phage types, including DT170 (44.6% of all isolates), DT135 (13.9%), DT9 (10.8%),
      DT44 (4.5%) and DT126 (4.5%). There was a difference in the discriminatory power
      of MLVA types within endemic phage types: Simpson's index of diversity ranged
      from 0.109 and 0.113 for DTs 9 and 135 to 0.172 and 0.269 for DTs 170 and 44,
      respectively. 66 distinct STM clusters were observed ranging in size from 5 to
      180 cases and in duration from 4 weeks to 25 weeks. 43 clusters had novel MLVA
      types and 23 represented recurrences of previously recorded MLVA types. The
      diversity of the STM population remained relatively constant over time. The
      gradual increase in the number of STM cases during the study was not related to
      significant changes in the number of clusters or their size. 667 different MLVA
      types or patterns were observed. CONCLUSIONS: Prospective MLVA typing of STM
      allows the detection of community outbreaks and demonstrates the sustained level
      of STM diversity that accompanies the increasing incidence of human STM
      infections. The monitoring of novel and persistent MLVA types offers a new
      benchmark for STM surveillance.A part of this study was presented at the MEEGID *
      (Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases)
      Conference, 3-5 November 2010, Amsterdam, The Netherlands.

PMID- 22462488
TI  - Small variations between species/subtypes attributed to reassortment evidenced
      from polymerase basic protein 1 with other seven proteins from influenza a virus.
AB  - This is a continuation of our studies previously published in this journal to use
      data analysis to explore why the reassortment of genetic segments from different
      host species and from different subtypes of influenza A viruses occurred
      frequently, which was considered the main reason for the generation of new
      strains. Of eleven proteins from influenza A virus, we have studied seven
      proteins in our previous studies. To get a full picture, 2352 polymerase basic
      proteins 1 from influenza A viruses were analysed. The results showed that the
      variations between host species/subtypes are smaller than those within host
      species/subtype. In combination with the results obtained from hemagglutinin,
      neuraminidase, nucleoprotein, matrix proteins 1 and 2, polymerase acidic protein
      and polymerase basic proteins 1 and 2, the results suggested that the
      predisposition to reassortment of genetic segments of influenza A virus from
      different host species and subtypes was mainly because of the small variations
      between the virus isolates.

PMID- 22462489
TI  - Breastfeeding and educational achievement at age 5.
AB  - Our aim was to investigate whether the duration of breastfeeding, at all or
      exclusively, is associated with educational achievement at age 5. We used data
      from a prospective, population-based UK cohort study, the Millennium Cohort Study
      (MCS). 5489 children from White ethnic background born at term in 2000-2001,
      attending school in England in 2006, were included in our analyses. Educational
      achievement was measured using the Foundation Stage Profile (FSP), a statutory
      assessment undertaken by teachers at the end of the child's first school year.
      Breastfeeding duration was ascertained from interviews with the mother when the
      child was 9 months old. We used modified Poisson's regression to model the
      association of breastfeeding duration with having reached a good level of
      achievement overall (>=78 overall points and >=6 in 'personal, social and
      emotional development' and 'communication, language and literacy' points) and in
      specific areas (>=6 points) of development. Children who had been breastfed for
      up to 2 months were more likely to have reached a good level of overall
      achievement [adjusted rate ratio (RR): 1.09, 95% confidence interval (CI): 1.01,
      1.19] than never breastfed children. This association was more marked in children
      breastfed for 2-4 months (adjusted RR: 1.17, 95% CI: 1.07, 1.29) and in those
      breastfed for longer than 4 months (adjusted RR: 1.16, 95% CI: 1.07, 1.26). The
      associations of exclusive breastfeeding with the educational achievement were
      similar. Our findings suggest that longer duration of breastfeeding, at all or
      exclusively, is associated with better educational achievement at age 5. 

PMID- 22462490
TI  - What does God know? Supernatural agents' access to socially strategic and non
      strategic information.
AB  - Current evolutionary and cognitive theories of religion posit that supernatural
      agent concepts emerge from cognitive systems such as theory of mind and social
      cognition. Some argue that these concepts evolved to maintain social order by
      minimizing antisocial behavior. If these theories are correct, then people should
      process information about supernatural agents' socially strategic knowledge more
      quickly than non-strategic knowledge. Furthermore, agents' knowledge of immoral
      and uncooperative social behaviors should be especially accessible to people. To
      examine these hypotheses, we measured response-times to questions about the
      knowledge attributed to four different agents--God, Santa Claus, a fictional
      surveillance government, and omniscient but non-interfering aliens--that vary in
      their omniscience, moral concern, ability to punish, and how supernatural they
      are. As anticipated, participants respond more quickly to questions about agents'
      socially strategic knowledge than non-strategic knowledge, but only when agents
      are able to punish.

PMID- 22462491
TI  - Cone-beam computed tomography in hypofractionated stereotactic radiotherapy for
      brain metastases.
AB  - BACKGROUND: To assess interfraction translational and rotational setup errors, in
      patients treated with image-guded hypofractionated stereotactic radiotherapy,
      immobilized by a thermoplastic mask and a bite-block and positioned using
      stereotactic coordinates. METHODS: 37 patients with 47 brain metastases were
      treated with hypofractionated stererotactic radiotherapy. All patients were
      immobilized with a combination of a thermoplastic mask and a bite-block fixed to
      a stereotactic frame support. Daily cone-beam CT scans were acquired for every
      patient before the treatment session and were matched online with planning CT
      images, for 3D image registration. The mean value and standard deviation of all
      translational (X, Y, Z) and rotational errors (thetax, thetay, thetaz) were
      calculated for the matching results of bone matching algorithm. RESULTS: A total
      of 194 CBCT scans were analyzed. Mean +/- standard deviation of translational
      errors (X, Y, Z) were respectively 0.5 +/- 1.6 mm (range -5.7 and 5.9 mm) in X;
      0.4 +/- 2.7 mm (range -8.2 and 12.1 mm) in Y; 0.4 +/- 1.9 mm (range -7.0 and 14
      mm) in Z; median and 90th percentile were respectively within 0.5 mm and 2.4 mm
      in X, 0.3 mm and 3.2 mm in Y, 0.3 mm and 2.2 mm in Z. Mean +/- standard deviation
      of rotational errors (thetax, thetay, thetaz) were respectively 0.0 degrees+/-
      1.3 degrees (thetax) (range -6.0 degrees and 3.1 degrees); -0.1 degrees +/- 1.1
      degrees (thetay) (range -3.0 degrees and 2.4 degrees); -0.6 degrees +/- 1.4
      degrees (thetaz) (range -5.0 degrees and 3.3 degrees). Median and 90th percentile
      of rotational errors were respectively within 0.1 degrees and 1.4 degrees
      (thetax), 0.0 degrees and 1.2 degrees (thetay), 0.0 degrees and 0.9 degrees
      (thetaz). Mean +/- SD of 3D vector was 3.1 +/- 2.1 mm (range 0.3 and 14.9 mm);
      median and 90th percentile of 3D vector was within 2.7 mm and 5.1 mm.
      CONCLUSIONS: Hypofractionated stereotactic radiotherapy have the significant
      limitation of uncertainty in interfraction repeatability of the patient setup;
      image-guided radiotherapy using cone-beam computed tomography improves the
      accuracy of the treatment delivery reducing set-up uncertainty, giving the
      possibility of 3-dimensional anatomic informations in the treatment position.

PMID- 22462492
TI  - Enhanced expression of salusin-beta contributes to progression of atherosclerosis
      in LDL receptor deficient mice.
AB  - Atherosclerosis is an important underlying pathology of cardiovascular diseases.
      The aim of this study was to observe the expression of salusin-beta, a new
      vasoactive peptide, in vascular tissues of low-density lipoprotein receptor
      deficient (LDLR(-/-)) mice, and to evaluate the effect of salusin-beta on the
      development of atherosclerosis in LDLR(-/-) mice. Six-week-old, male LDLR(-/-)
      mice were subcutaneously injected with salusin-beta or the vehicle, once a day
      for 12 weeks. The expressions of salusin-beta in both mRNA and peptide levels
      were determined by reverse transcription - polymerase chain reaction, Western
      blot, and immunohistochemistry. Atherosclerotic lesions were analyzed by staining
      with hematoxylin and eosin or oil red O. Our results showed that expression of
      salusin-beta in mRNA and salusin-beta peptide levels were enhanced in LDLR(-/-)
      mice. Subcutaneous injection of salusin-beta significantly aggravated the
      atherosclerotic lesions, and increased lipid deposits in the arteries of LDLR(-/
      ) mice. Moreover, salusin-beta significantly increased the serum level of low
      density lipoprotein cholesterol, but not total cholesterol, triglycerides, or
      high-density lipoprotein cholesterol. These results suggest that the enhanced
      expression of salusin-beta contributes to progression of atherosclerosis in LDLR(
      /-) mice by up-regulating the serum low-density lipoprotein cholesterol level.
      This study provides a potential therapeutic target for the prevention and
      treatment of atherosclerosis.

PMID- 22462493
TI  - Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding
      protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish
      population.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is predominantly caused by a large
      number of various mutations in the genes encoding sarcomeric proteins. However,
      two prevalent founder mutations for HCM in the alpha-tropomyosin (TPM1-D175N) and
      myosin-binding protein C (MYBPC3-Q1061X) genes have previously been identified in
      eastern Finland. OBJECTIVE: To assess the prevalence of these founder mutations
      in a large population of patients with HCM from all over Finland. Patients and
      methods. We screened for two founder mutations (TPM1-D175N and MYBPC3-Q1061X) in
      306 unrelated Finnish patients with HCM from the regions covering a population of
      ~4,000,000. RESULTS: The TPM1-D175N mutation was found in 20 patients (6.5%) and
      the MYBPC3-Q1061X in 35 patients (11.4%). Altogether, the two mutations accounted
      for 17.9% of the HCM cases. In addition, 61 and 59 relatives of the probands were
      found to be carriers of TPM1-D175N and MYBPC3-Q1061X, respectively. The mutations
      showed regional clustering. TPM1-D175N was prevalent in central and western
      Finland, and MYBPC3-Q1061X in central and eastern Finland. CONCLUSION: The TPM1
      D175N and MYBPC3-Q1061X mutations account for a substantial part of all HCM cases
      in the Finnish population, indicating that routine genetic screening of these
      mutations is warranted in Finnish patients with HCM.

PMID- 22462494
TI  - Some Canadian-grown potato cultivars contribute to a substantial content of
      essential dietary minerals.
AB  - Potato consumption provides significant dietary contributions to several
      essential minerals, but the effects of cultivar and planting site are not well
      understood. The mineral content of 16 cultivars, grown at 5 locations, was
      measured using inductively coupled plasma-optical emission spectroscopy and
      evaluated on a per serving basis for percent recommended daily intake (% RDI),
      emphasizing some minerals where global deficiencies are common (calcium, iron,
      selenium, and zinc). Discriminant analysis showed that both genotype and growing
      location were important. Differences in mineral content occurred between
      cultivars at each site, specific cultivars at different sites, and collectively
      between sites. 'Freedom', 'Yukon Gold', and particularly the very stable mineral
      source 'Russet Burbank' contributed most to the % RDI for minerals. One serving
      per day of these cultivars provides a significant contribution to the % RDI for
      the macrominerals magnesium, phosphorus, and potassium and the trace minerals
      copper, iron, selenium, and zinc.

PMID- 22462495
TI  - Interleukin-17 regulates visceral obesity in HIV-1-infected patients.
AB  - OBJECTIVE: The aim of the study was to evaluate the interleukin-17 (IL-17) plasma
      level in HIV-1-infected patients and its relation to central obesity. METHODS:
      Eighty-four HIV-1-infected patients [42 with visceral obesity (group A) and 42
      without visceral obesity (group B)] and 46 HIV-negative subjects [23 with
      visceral obesity (group C) and 23 without visceral obesity (group D)] were
      enrolled in the study. Sonographic measurements of perirenal fat diameter/body
      mass index (PRFD/BMI) were used to assess visceral adipose tissue thickness.
      RESULTS: HIV-1-infected patients had higher plasma levels of IL-17 than HIV
      negative subjects [837.8 +/- 260 pg/mL (mean +/- standard deviation) vs. 395.3 +/
      138.6 pg/mL, respectively; P<0.001]. Furthermore, HIV-1-infected patients with a
      diagnosis of visceral obesity had lower levels of IL-17 than HIV-infected lean
      patients (756.9 +/- 282.9 pg/mL vs. 918.7 +/- 208.4 pg/mL, respectively; P<0.01).
      IL-17 (r= -0.21; P=0.03) and waist circumference (r=0.48; P<0.001) were
      significantly associated with visceral adipose tissue thickness. A negative
      correlation of IL-17 (r= -0.23; P<0.001) with PRFD/BMI was found. CONCLUSIONS:
      This study suggests a linear negative association between IL-17 and visceral
      adipose tissue thickness.

PMID- 22462496
TI  - Bone physiology in human grafted and non-grafted extraction sockets--an
      immunohistochemical study.
AB  - PURPOSE: The aim of the present immunohistological investigation was to define
      and compare the osteogenic potential with the vascularization of the provisional
      matrix in grafted and ungrafted extraction sockets after 4 and 12 weeks of
      healing. METHODS: A total of 33 Patients (15 women, 18 men) with 65 extraction
      sites with a mean age of 54.4 years (30-73 years) participated in this study.
      After tooth extraction, the sockets were augmented with Bio-Oss collagen or non
      augmented. At implant placement after 4 or 12 weeks bone biopsies were obtained.
      Within the specimens the osteogenic and endothelial potential of mesenchymal
      cells was analyzed in the provisional matrix using immunohistochemical analysis
      with three monoclonal antibodies Cbfa1/Runx2, Osteocalcin (OC), and CD31.
      Statistical analysis was performed using Mann-Whitney U-test, Spearman's rank
      order correlation coefficient, and the two-factorial analysis for repeated
      measurements. RESULTS: Of the 65 extraction sockets, 25 (13 non-augmented, 12
      augmented) sites after 4 weeks healing time and 40 (19 non-augmented, 21
      augmented) sites after 12 weeks healing time were involved in the study. No signs
      of acute or chronic inflammation were noted in any specimens. After 4 weeks, a
      median amount of 56% (10-85%) of Cbfa1 positive cells and a median amount of
      cells expressing OC of 21% (5-42%) were measured. A median CD31 score of 5 was
      observed. After 12 weeks, a median amount of 61% (19-90%) positive cells
      expressed by Cbfa1/Runx2 staining a median amount of OC positive cells of 9% (2
      17%) was measured. The results at 12 weeks revealed a median score of CD31
      positive cells of 3. DISCUSSION: Osteoblastic activity in the provisional matrix
      was highest after 4 weeks of healing period. The active zone of bone formation is
      found in the apical region of the extraction socket during the early healing
      phase, shifting to the coronal region after 12 weeks. A peak of osteoblast
      activity within the first weeks is followed by a reduction in mature osteoblasts
      with osteoblasts remaining in an inactive stage. The vascularity changed in
      likewise fashion to the maturation of osteoblasts within the observation period.
      The results have shown that with increasing age a decreasing endothelial
      potential was observed not after 4 weeks, but after 12 weeks, thus it suggests
      that angiogenesis is diminished in older patients in the later phase of healing
      in extraction sockets.

PMID- 22462497
TI  - Dicer-1 is a key enzyme in the regulation of oogenesis in panoistic ovaries.
AB  - BACKGROUND INFORMATION: In insects, the action of microRNAs (miRNAs) on oogenesis
      has been explored only in dipterans, which possess meroistic ovaries, a highly
      modified ovarian type. Here we study miRNA function in the most primitive,
      panoistic type of ovaries using the phylogenetically basal insect Blattella
      germanica (Dictyoptera, Blattellidae) as model. RESULTS: Dicer-1 (Dcr1), a key
      enzyme in miRNA biogenesis, was depleted using RNAi. Females treated with double
      stranded RNA targeting Dicer-1, exhibited deep alterations in oocyte development;
      among them, the follicular epithelia of the basal oocytes did not develop, thus
      resulting in sterile females. CONCLUSIONS: These effects derived from the absence
      of Dicer-1 suggest that miRNAs are crucial for the regulation of oogenesis in
      panoistic ovaries, the most primitive insect ovarian type.

PMID- 22462498
TI  - Suspension cultures of bone-marrow-derived mesenchymal stem cells: effects of
      donor age and glucose level.
AB  - Both ageing and diabetes are associated with reduced numbers and functional
      viability of mesenchymal stem cells (MSCs) in vivo which in turn lead to
      degenerative pathologies of the musculoskeletal system. The overall aim of this
      study was to elucidate the effects of age and raised glucose levels on the
      proliferation and self-renewal of rat nonadherent bone marrow MSCs (Na-BM-MSCs)
      in suspension cultures. MSC cultures isolated from 3- and 12-month-old rats were
      maintained using the "pour-off" method for up to 14 days in media containing
      different glucose levels and the phenotype, growth characteristics, colony
      forming unit-fibroblastic (CFU-f) numbers, and pluripotency characteristics of
      these cells were determined. This study indicates that rat adult bone marrow
      harbors pluripotent Na-BM-MSCs that seem to be unaffected by ageing during in
      vitro expansion. The Na-BM-MSCs express the pluripotency markers Oct4, Sox2, and
      Nanog. It was found that culture in high-glucose-containing medium had a negative
      effect on colony formation and differentiation. In contrast to classical MSC
      cultures, the generation of colonies by Na-BM-MSCs in suspension culture was not
      reduced in the older animals. The Na-BM-MSCs were found to express the
      pluripotency markers Oct4, Sox2, and Nanog, suggesting a more primitive stage of
      differentiation as compared with adherent MSCs. These data indicate that rat
      adult bone marrow harbors a population of pluripotent Na-BM-MSCs that appear to
      be relatively unaffected by ageing during in vitro expansion in suspension.

PMID- 22462499
TI  - Epimerization free synthesis of O-acyl isodipeptides employing COMU.
AB  - O-Acyl isodipeptides are prepared by coupling Boc-Ser/Thr-OBzl with Fmoc-Xaa-OH
      employing COMU, well known third generation peptide coupling agent. The reaction
      proceeds with high yield and the chemical homogeneity of the synthesized
      molecules were established via chiral HPLC analyses. The O-acyl isodipeptide
      units play crucial role in the success of ' click peptide'  protocol employed for
      assembling ' difficult sequence'  peptides.

PMID- 22462500
TI  - Oxygen kinetic isotope effects upon catalytic water oxidation by a monomeric
      ruthenium complex.
AB  - Oxygen isotope fractionation is applied for the first time to probe the catalytic
      oxidation of water using a widely studied ruthenium complex,
      [Ru(II)(tpy)(bpy)(H(2)O)](ClO(4))(2) (bpy = 2,2'-bipyridine; tpy = 2,2';6",2"
      terpyridine). Competitive oxygen-18 kinetic isotope effects ((18)O KIEs) derived
      from the ratio of (16,16)O(2) to (16,18)O(2) formed from natural-abundance water
      vary from 1.0132 +/- 0.0005 to 1.0312 +/- 0.0004. Experiments were conducted with
      cerium(IV) salts at low pH and a photogenerated ruthenium(III) tris(bipyridine)
      complex at neutral pH as the oxidants. The results are interpreted within the
      context of catalytic mechanisms using an adiabatic formalism to ensure the
      highest barriers for electron-transfer and proton-coupled electron-transfer
      steps. In view of these contributions, O-O bond formation is predicted to be
      irreversible and turnover-limiting. The reaction with the largest (18)O KIE
      exhibits the greatest degree of O-O coupling in the transition state. Smaller
      (18)O KIEs are observed due to multiple rate-limiting steps or transition-state
      structures which do not involve significant O-O motion. These findings provide
      benchmarks for systematizing mechanisms of O-O bond formation, the critical step
      in water oxidation by natural and synthetic catalysts. In addition, the
      measurements introduce a new tool for calibrating computational studies using
      relevant experimental data.

PMID- 22462501
TI  - Determination of the deposition order of overlapping latent fingerprints and inks
      using secondary ion mass spectrometry.
AB  - A new protocol using time-of-flight secondary ion mass spectrometry (ToF-SIMS)
      has been developed to identify the deposition order of a fingerprint overlapping
      an ink line on paper. By taking line scans of fragment ions characteristic of the
      ink molecules (m/z 358.2 and 372.2) where the fingerprint and ink overlap and by
      calculating the normalized standard deviation of the intensity variation across
      the line scan, it is possible to determine whether or not a fingerprint is above
      ink on a paper substrate. The protocol adopted works for a selection of
      fingerprints from four donors tested here and for a fingerprint that was aged for
      six months; for one donor, the very faint fingerprints could not be visualized
      using either standard procedures (ninhydrin development) or SIMS, and therefore
      the protocol correctly gives an inconclusive result.

PMID- 22462502
TI  - Analysis of immediate stress mechanisms upon injection of polymeric micelles and
      related colloidal drug carriers: implications on drug targeting.
AB  - Polymeric micelles are ideal carriers for solubilization and targeting
      applications using hydrophobic drugs. Stability of colloidal aggregates upon
      injection into the bloodstream is mandatory to maintain the drugs' targeting
      potential and to influence pharmacokinetics. In this review we analyzed and
      discussed the most relevant stress mechanisms that polymeric micelles and related
      colloidal carriers encounter upon injection, including (1) dilution, (2)
      interactions with blood components, and (3) immunological responses of the body.
      In detail we analyzed the opsonin-dysopsonin hypothesis that points at a
      connection between a particles' protein-corona and its tissue accumulation by the
      enhanced permeability and retention (EPR) effect. In the established theory, size
      is seen as a necessary condition to reach nanoparticle accumulation in disease
      modified tissue. There is, however, mounting evidence of other sufficient
      conditions (e.g., particle charge, receptor recognition of proteins adsorbed onto
      particle surfaces) triggering nanoparticle extravasation by active mechanisms. In
      conclusion, the analyzed stress mechanisms are directly responsible for in vivo
      success or failure of the site-specific delivery with colloidal carrier systems.

PMID- 22462503
TI  - Gaze following, gaze reading, and word learning in children at risk for autism.
AB  - This study investigated gaze-following abilities as a prerequisite for word
      learning, in a population expected to manifest a wide range of social and
      communicative skills-children with a family history of autism. Fifty-three 3-year
      olds with or without a family history of autism took part in a televised word
      learning task. Using an eye-tracker to monitor children's gaze behavior, it was
      shown that the ability to follow gaze was necessary but not sufficient for
      successful word learning. Those children who had poor social and communicative
      skills followed gaze to the labeled object but did not then learn the associated
      word. These findings shed light on the conditions that lead to successful word
      learning in typical and atypical populations.

PMID- 22462504
TI  - At what time is the cocktail party? A late locus of selective attention to
      natural speech.
AB  - Distinguishing between speakers and focusing attention on one speaker in multi
      speaker environments is extremely important in everyday life. Exactly how the
      brain accomplishes this feat and, in particular, the precise temporal dynamics of
      this attentional deployment are as yet unknown. A long history of behavioral
      research using dichotic listening paradigms has debated whether selective
      attention to speech operates at an early stage of processing based on the
      physical characteristics of the stimulus or at a later stage during semantic
      processing. With its poor temporal resolution fMRI has contributed little to the
      debate, while EEG-ERP paradigms have been hampered by the need to average the EEG
      in response to discrete stimuli which are superimposed onto ongoing speech. This
      presents a number of problems, foremost among which is that early attention
      effects in the form of endogenously generated potentials can be so temporally
      broad as to mask later attention effects based on the higher level processing of
      the speech stream. Here we overcome this issue by utilizing the AESPA (auditory
      evoked spread spectrum analysis) method which allows us to extract temporally
      detailed responses to two concurrently presented speech streams in natural
      cocktail-party-like attentional conditions without the need for superimposed
      probes. We show attentional effects on exogenous stimulus processing in the 200
      220 ms range in the left hemisphere. We discuss these effects within the context
      of research on auditory scene analysis and in terms of a flexible locus of
      attention that can be deployed at a particular processing stage depending on the
      task.

PMID- 22462505
TI  - Improved survival following cerebral edema using a novel hollow fiber-hydrogel
      device.
AB  - OBJECT: Cerebral edema is a significant cause of morbidity and mortality in many
      disease states. Current therapies of cerebral edema are often ineffective in
      treating severe edema. Here, the authors develop a hollow fiber-hydrogel device
      (HFHD) for direct surface contact-based treatment of severe cerebral edema.
      METHODS: Brain edema was induced in adult mice via water intoxication by
      intraperitoneal water administration (30% body weight). Control mice received no
      treatment. A distinct group of mice was treated with craniectomy but no device
      application (craniectomy only). A third experimental group was treated with
      craniectomy and HFHD application. The HFHD contained a lumen solution of 350 g/L
      bovine serum albumin in room-temperature artificial CSF at pH 7.4. Survival and
      brain water content were assessed as end points. RESULTS: Craniectomy and
      application of the HFHD enhanced survival in animals with severe cerebral edema.
      Animals treated with a craniectomy and HFHD (n = 5) survived up to 5 hours longer
      than animals treated with craniectomy only (n = 5) (p < 0.001) or no treatment (n
      = 5) (p < 0.001). Animals treated with craniectomy and HFHD (n = 5) had a
      survival rate of 80% within the observation period (360 minutes), whereas no
      animal treated with craniectomy only (n = 5) or no treatment (n = 5) survived
      longer than 50 and 33 minutes, respectively. Statistical significance was
      observed for the survival rate between the animals treated with a craniectomy +
      HFHD (n = 5) versus those treated with craniectomy only (n = 5) (p < 0.001), and
      craniectomy + HFHD versus no treatment (n = 5) (p < 0.001). Histological analysis
      demonstrated no significant cell loss in the cortex subjacent to HFHD
      application. CONCLUSIONS: Here, the authors demonstrate the feasibility of their
      HFHD to treat cerebral edema in this model. These results indicate that
      controlled water extraction from edematous brain tissue can be performed and can
      lead to increased survival compared with craniectomy only. Further studies remain
      to be performed to further optimize the HFHD and to test it in more clinically
      relevant models, such as traumatic brain injury.

PMID- 22462506
TI  - Cranial decompression for the treatment of malignant intracranial hypertension
      after ischemic cerebral infarction: decompressive craniectomy and hinge
      craniotomy.
AB  - OBJECT: Recent randomized trials have demonstrated a positive role (improved
      survival) in patients treated with cranial decompression for malignant cerebral
      infarction. However, many variables regarding operative decompression in this
      setting remain to be determined. Hinge craniotomy is an alternative to
      decompressive craniectomy, but its role in space-occupying cerebral infarctions
      has not been delineated. The objective of this study was to compare the authors'
      experiences with these 2 procedures in the management of space-occupying cerebral
      infarctions to determine the efficacy of each. METHODS: The authors conducted a
      retrospective review of 28 cases involving patients who underwent cranial
      decompression (hinge craniotomy in 9 cases, decompressive craniectomy in 19) for
      treatment of malignant intracranial hypertension after ischemic cerebral
      infarction. RESULTS: No significant differences were identified in baseline
      demographics, neurological examination, or Rotterdam score between the hinge
      craniotomy and decompressive craniectomy groups. Both treatments resulted in
      adequate control of intracranial pressure (ICP). The need for reoperation for
      persistent intracranial hypertension and duration of mechanical ventilation and
      intensive care unit stay were similar. Hospital survival was significantly higher
      in the decompressive craniectomy group (89% vs 56%), whereas long-term functional
      outcome was better in the hinge craniotomy group. Cranial defect size was
      comparable in the 2 groups. Postoperative imaging revealed a higher rate of
      subarachnoid hemorrhage, contusion/hematoma progression, and subdural
      effusions/hygromas after decompressive craniectomy. The requirement for cranial
      revision in survivors was higher for patients undergoing decompressive
      craniectomy (100%) than those undergoing hinge craniotomy (20%). CONCLUSIONS:
      Hinge craniotomy appears to be at least as good as decompressive craniectomy in
      providing postoperative ICP control at a similar therapeutic index. Although the
      in-hospital mortality was higher in patients treated with hinge craniotomy, that
      procedure resulted in superior long-term functional outcomes and may help limit
      postoperative complications.

PMID- 22462507
TI  - The effect of increased mobility on morbidity in the neurointensive care unit.
AB  - OBJECT: The detrimental effects of immobility on intensive care unit (ICU)
      patients are well established. Limited studies involving medical ICUs have
      demonstrated the safety and benefit of mobility protocols. Currently no study has
      investigated the role of increased mobility in the neurointensive care unit
      population. This study was a single-institution prospective intervention trial to
      investigate the effectiveness of increased mobility among neurointensive care
      unit patients. METHODS: All patients admitted to the neurointensive care unit of
      a tertiary care center over a 16-month period (April 2010 through July 2011) were
      evaluated. The study consisted of a 10-month (8025 patient days) preintervention
      observation period followed by a 6-month (4455 patient days) postintervention
      period. The intervention was a comprehensive mobility initiative utilizing the
      Progressive Upright Mobility Protocol (PUMP) Plus. RESULTS: Implementation of the
      PUMP Plus increased mobility among neurointensive care unit patients by 300% (p <
      0.0001). Initiation of this protocol also correlated with a reduction in
      neurointensive care unit length of stay (LOS; p < 0.004), hospital LOS (p <
      0.004), hospital-acquired infections (p < 0.05), and ventilator-associated
      pneumonias (p < 0.001), and decreased the number of patient days in restraints (p
      < 0.05). Additionally, increased mobility did not lead to increases in adverse
      events as measured by falls or inadvertent line disconnections. CONCLUSIONS:
      Among neurointensive care unit patients, increased mobility can be achieved
      quickly and safely with associated reductions in LOS and hospital-acquired
      infections using the PUMP Plus program.

PMID- 22462508
TI  - Chiropractor and dissections.

PMID- 22462509
TI  - Chiropractor and dissections.

PMID- 22462510
TI  - Tic and autonomic symptoms.

PMID- 22462511
TI  - Delayed neuromotor recovery and increased memory acquisition dysfunction
      following experimental brain trauma in mice lacking the DNA repair gene XPA.
AB  - OBJECT: This study investigates the outcome after traumatic brain injury (TBI) in
      mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA).
      As damage to DNA has been implicated in neuronal cell death in various models,
      the authors sought to elucidate whether the absence of an essential DNA repair
      factor would affect the outcome of TBI in an experimental setting. METHODS:
      Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock
      out" [n = 19]) genotype were subjected to controlled cortical impact experimental
      brain trauma, which produced a focal brain injury. Sham-injured mice of both
      genotypes were used as controls (9 in each group). The mice were subjected to
      neurobehavoral tests evaluating learning/acquisition (Morris water maze) and
      motor dysfunction (Rotarod and composite neuroscore test), pre- and postinjury up
      to 4 weeks. The mice were killed after 1 or 4 weeks, and cortical lesion volume,
      as well as hippocampal and thalamic cell loss, was evaluated. Hippocampal
      staining with doublecortin antibody was used to evaluate neurogenesis after the
      insult. RESULTS: Brain-injured XPA(-/-) mice exhibited delayed recovery from
      impairment in neurological motor function, as well as pronounced cognitive
      dysfunction in a spatial learning task (Morris water maze), compared with injured
      XPA(+/+) mice (p < 0.05). No differences in cortical lesion volume, hippocampal
      damage, or thalamic cell loss were detected between XPA(+/+) and XPA(-/-) mice
      after brain injury. Also, no difference in the number of cells stained with
      doublecortin in the hippocampus was detected. CONCLUSIONS: The authors' results
      suggest that lack of the DNA repair factor XPA may delay neurobehavioral recovery
      after TBI, although they do not support the notion that this DNA repair
      deficiency results in increased cell or tissue death in the posttraumatic brain.

PMID- 22462513
TI  - Alternative donor HSCT in refractory acquired aplastic anemia - prevention of
      graft rejection and graft versus host disease by immunoablative conditioning and
      graft manipulation.
AB  - Early alternative donor HSCT is a potentially curative therapeutic option for
      patients with AAA not responding to IST. Seven patients (median age at diagnosis,
      11 yr) with refractory AAA without a MSD underwent HSCT from matched unrelated (n
      = 6) or haploidentical (n = 1) donors. Conditioning regimens included CY (n = 7),
      muromonab-CD3/ATG (n = 7), TT (n = 6), FLU (n = 5), and TLI (n = 2). Grafts were
      either CD34 purified and/or CD3/19 depleted and contained a median of 10.17 *
      10(6) /kg CD34 and 5.5 * 10(4) /kg CD3 cells. All patients engrafted rapidly.
      Median time to leukocyte engraftment was 10 days. With a median follow-up of 26
      (range, 11-153) months, six patients are alive and well with complete donor
      hematopoiesis. One heavily pretreated patient developed GVHD grade III and died
      from progressive renal failure (resulting from microangiopathic hemolytic anemia)
      and disseminated aspergillosis. Early alternative donor HSCT can help to avoid
      complications from prolonged IST and presumably improve survival of patients with
      refractory AAA. Administration of high doses of CD34 purified and/or CD3/19
      depleted stem cells following novel immunoablative conditioning may prevent graft
      rejection and GVHD. However, a long interval from diagnosis to HSCT seems to be
      associated with poor outcome.

PMID- 22462512
TI  - Factors associated with non-response in routine use of patient reported outcome
      measures after elective surgery in England.
AB  - BACKGROUND: Patient-reported outcome measures are increasingly being used to
      compare providers. We studied whether non-response rates to post-operative
      questionnaires are associated with patients' characteristics and organisational
      features of providers. METHODS: 131,447 patients who underwent a hip or knee
      replacement, hernia repair or varicose vein surgery in 2009-10 in England.
      Multivariable logistic regression to calculate adjusted odds ratios of non
      response for characteristics of the patients and organisational characteristics
      of providers. Multiple imputation was used for missing patient characteristics.
      Providers were included as random effects. RESULTS: Response rates to the post
      operative questionnaire were 85.1% for hip replacement (n = 37 961), 85.3% for
      knee replacements (n = 44 422), 72.9% for hernia repair (n = 34 964), and 64.8%
      for varicose vein surgery (n = 14 100). Across the four procedures, there were
      higher levels of non-response in men (odds ratios 1.03 [95% CI 0.95-1.11] - 1.35
      [1.25-1.46]), younger patients (those under 55 years 3.01 [2.72-3.32] - 6.05
      [5.49-6.67]), non-white patients (1.24 [1.11-1.38] - 2.08 [1.89-2.31]), patients
      in the most deprived quintile of socio-economic status (1.47 [1.34-1,62] - 1.86
      [1.71-2.03]), those who lived alone (1.11 [0.99-1.23] - 1.27 [1.18-1.36]) and
      those who had been assisted when completing their pre-operative questionnaire
      (1.26 [1.10-1.46] -1.67 [1.56-1.79]). Non-response rates were also higher in
      patients who had poorer pre-operative health (three or more comorbidities: 1.14
      [0.96-1.35] - 1.45 [1.30-1.63]). Providers' patient recruitment rates before
      surgery and the timing of pre-operative questionnaire administration did not
      affect the rates of response to post-operative questionnaires. CONCLUSION: If non
      response can be shown to be associated with outcome, then rates of non-response
      to post-operative questionnaires would need to be taken into account when these
      measures are being used to compare the performance of providers or to evaluate
      surgical procedures.

PMID- 22462514
TI  - Language learning and control in monolinguals and bilinguals.
AB  - Parallel language activation in bilinguals leads to competition between
      languages. Experience managing this interference may aid novel language learning
      by improving the ability to suppress competition from known languages. To
      investigate the effect of bilingualism on the ability to control native-language
      interference, monolinguals and bilinguals were taught an artificial language
      designed to elicit between-language competition. Partial activation of
      interlingual competitors was assessed with eye-tracking and mouse-tracking during
      a word recognition task in the novel language. Eye-tracking results showed that
      monolinguals looked at competitors more than bilinguals, and for a longer
      duration of time. Mouse-tracking results showed that monolinguals' mouse
      movements were attracted to native-language competitors, whereas bilinguals
      overcame competitor interference by increasing the activation of target items.
      Results suggest that bilinguals manage cross-linguistic interference more
      effectively than monolinguals. We conclude that language interference can affect
      lexical retrieval, but bilingualism may reduce this interference by facilitating
      access to a newly learned language.

PMID- 22462515
TI  - Thermotropic behavior of a cationic surfactant in the adsorbed and micellar
      state: an NMR study.
AB  - Knowledge about how temperature affects the internal structure and dynamics of
      surfactant aggregates can lead to a better understanding of their behavior in
      complex environments and processes. (13)C chemical shifts of the cationic
      surfactant tetradecytrimethylammonium bromide (TTAB) in micellar solution and
      when adsorbed on silica particles are recorded in the temperature range 8-78 
      degrees C, and give information on the conformation of the alkyl chain carbons.
      Adsorbed TTAB has conformational disorder similar to free TTAB at about 70 
      degrees C, with an increase in the rate of conformational changes occurring above
      50  degrees C. Furthermore, no significant change in TTAB adsorption density was
      observed in the temperature range studied, and the results indicate a bilayer
      arrangement of the adsorbed surfactants. The number of gauche conformers
      increases linearly with temperature for the alkyl chain carbons in TTAB micelles.
      However, the total increase in gauche conformers is significantly smaller for
      micellar than for adsorbed TTAB within the temperature range studied. The
      fraction of micellized TTAB molecules in solution is found to increase with
      temperature. 

PMID- 22462516
TI  - Comprehensive geriatric assessment, multifactorial interventions and nurse-led
      care coordination to prevent functional decline in community-dwelling older
      persons: protocol of a cluster randomized trial.
AB  - BACKGROUND: Functional decline in community-dwelling older persons is associated
      with the loss of independence, the need for hospital and nursing-home care and
      premature death. The effectiveness of multifactorial interventions in preventing
      functional decline remains controversial. The aim of this study is to investigate
      whether functional decline in community-dwelling older persons can be delayed or
      prevented by a comprehensive geriatric assessment, multifactorial interventions
      and nurse-led care coordination. METHODS/DESIGN: In a cluster randomized
      controlled trial, with the general practice as the unit of randomization, 1281
      participants from 25 general practices will be enrolled in each condition to
      compare the intervention with usual care. The intervention will focus on older
      persons who are at increased risk for functional decline, identified by an
      Identification of Seniors at Risk Primary Care (ISAR-PC) score (>= 2). These
      older persons will receive a comprehensive geriatric assessment, an individually
      tailored care and treatment plan, consisting of multifactorial, evidence-based
      interventions and subsequent nurse-led care coordination. The control group will
      receive 'care as usual' by the general practitioner (GP). The main outcome after
      12 months is the level of physical functioning on the modified Katz-15 index
      score. The secondary outcomes are health-related quality of life, psychological
      and social functioning, healthcare utilization and institutionalization.
      Furthermore, a process evaluation and cost-effectiveness analysis will be
      performed. DISCUSSION: This study will provide new knowledge regarding the
      effectiveness and feasibility of a comprehensive geriatric assessment,
      multifactorial interventions and nurse-led elderly care in general practice.
      TRIAL REGISTRATION: NTR2653 GRANT: Unrestricted grant 'The Netherlands
      Organisation for Health Research and development' no 313020201.

PMID- 22462518
TI  - Solvent exchange at some bivalent metal ions.

PMID- 22462517
TI  - Dietary patterns in infancy and their associations with maternal socio-economic
      and lifestyle factors among 758 Japanese mother-child pairs: the Osaka Maternal
      and Child Health Study.
AB  - Dietary habits established in early childhood contribute to lifelong dietary
      pattern and the development of early risk factors for disease in adulthood.
      Although a large body of epidemiologic data from Western countries show that the
      dietary pattern of children is influenced by maternal socio-economic and
      lifestyle characteristics, information on this topic in non-Western countries is
      absolutely lacking. The present study identified dietary patterns among infants
      aged 16-24 months, and then examined the influence of maternal socio-economic and
      lifestyle characteristics on identified dietary patterns. Subjects were 758
      Japanese mother-child pairs. Dietary data of infants were collected from the
      mothers using a questionnaire. Dietary patterns were extracted from the
      consumption of 15 foods (times week(-1)) by cluster analysis. The following two
      dietary patterns were identified: 'fruits, vegetables and high-protein foods' (n
      = 483) and 'confectionaries and sweetened beverages' (n = 275) patterns. After
      adjustment for all other predictors, maternal educational level, number of
      infants' siblings and maternal dietary patterns were independently associated
      with dietary patterns of infants. Infants whose mothers had a higher educational
      level and the 'rice, fish and vegetables' dietary pattern were less likely to
      belong to the 'confectionaries and sweetened beverages' pattern, whereas infants
      whose mothers had a higher number of children and the 'wheat product' dietary
      pattern were more likely to belong to the 'confectionaries and sweetened
      beverages' than the 'fruits, vegetables and high-protein foods' pattern. In
      conclusion, the mother's socio-economic position and dietary patterns were
      associated with the dietary patterns of infants in the Japanese pairs as observed
      in the Western populations.

PMID- 22462519
TI  - A phasing and imputation method for pedigreed populations that results in a
      single-stage genomic evaluation.
AB  - BACKGROUND: Efficient, robust, and accurate genotype imputation algorithms make
      large-scale application of genomic selection cost effective. An algorithm that
      imputes alleles or allele probabilities for all animals in the pedigree and for
      all genotyped single nucleotide polymorphisms (SNP) provides a framework to
      combine all pedigree, genomic, and phenotypic information into a single-stage
      genomic evaluation. METHODS: An algorithm was developed for imputation of
      genotypes in pedigreed populations that allows imputation for completely
      ungenotyped animals and for low-density genotyped animals, accommodates a wide
      variety of pedigree structures for genotyped animals, imputes unmapped SNP, and
      works for large datasets. The method involves simple phasing rules, long-range
      phasing and haplotype library imputation and segregation analysis. RESULTS:
      Imputation accuracy was high and computational cost was feasible for datasets
      with pedigrees of up to 25 000 animals. The resulting single-stage genomic
      evaluation increased the accuracy of estimated genomic breeding values compared
      to a scenario in which phenotypes on relatives that were not genotyped were
      ignored. CONCLUSIONS: The developed imputation algorithm and software and the
      resulting single-stage genomic evaluation method provide powerful new ways to
      exploit imputation and to obtain more accurate genetic evaluations.

PMID- 22462520
TI  - Candidate antibody-based therapeutics against HIV-1.
AB  - Antibody-based therapeutics have been successfully used for the treatment of
      various diseases and as research tools. Several well characterized, broadly
      neutralizing monoclonal antibodies (bnmAbs) targeting HIV-1 envelope
      glycoproteins or related host cell surface proteins show sterilizing protection
      of animals, but they are not effective when used for therapy of an established
      infection in humans. Recently, a number of novel bnmAbs, engineered antibody
      domains (eAds), and multifunctional fusion proteins have been reported which
      exhibit exceptionally potent and broad neutralizing activity against a wide range
      of HIV-1 isolates from diverse genetic subtypes. eAds could be more effective in
      vivo than conventional full-size antibodies generated by the human immune system.
      Because of their small size (12~15 kD), they can better access sterically
      restricted epitopes and penetrate densely packed tissue where HIV-1 replicates
      than the larger full-size antibodies. HIV-1 possesses a number of mechanisms to
      escape neutralization by full-size antibodies but could be less likely to develop
      resistance to eAds. Here, we review the in vitro and in vivo antiviral efficacies
      of existing HIV-1 bnmAbs, summarize the development of eAds and multispecific
      fusion proteins as novel types of HIV-1 inhibitors, and discuss possible
      strategies to generate more potent antibody-based candidate therapeutics against
      HIV-1, including some that could be used to eradicate the virus.

PMID- 22462522
TI  - Characterising ontogenetic niche shifts in Nile crocodile using stable isotope
      (delta13C, delta15N) analyses of scute keratin.
AB  - Nile crocodiles undergo a three to five order of magnitude increase in body size
      during their lifespan. This shift coincides with a change in resource and habitat
      use which influences the strength, type and symmetry of interactions with other
      species. Identifying size-specific crocodile groups displaying similar traits is
      important for conservation planning. Here, we illustrate how stable carbon
      (delta(13) C) and nitrogen (delta(15) N) isotope analysis of scute keratin,
      together with breakpoint modelling analysis can be used to characterise
      ontogenetic niche shifts. Using a sample set of 238 crocodiles from the Okavango
      Delta, Botswana (35-463 cm total length), we found prominent size-related changes
      in the scute keratin delta(13) C and delta(15) N profiles close to 40 and 119 cm
      snout-vent length. The first shift corroborated the findings of a traditional
      stomach-content study conducted on the same population at the same time, and the
      second conformed to known crocodile ecology. This approach can be used as a first
      approximation to identify size-specific groups within crocodile populations, and
      these can then be investigated further using isotopic or other methods.

PMID- 22462521
TI  - Factors that control catalytic two- versus four-electron reduction of dioxygen by
      copper complexes.
AB  - The selective two-electron reduction of O(2) by one-electron reductants such as
      decamethylferrocene (Fc*) and octamethylferrocene (Me(8)Fc) is efficiently
      catalyzed by a binuclear Cu(II) complex [Cu(II)(2)(LO)(OH)](2+) (D1) {LO is a
      binucleating ligand with copper-bridging phenolate moiety} in the presence of
      trifluoroacetic acid (HOTF) in acetone. The protonation of the hydroxide group of
      [Cu(II)(2)(LO)(OH)](2+) with HOTF to produce [Cu(II)(2)(LO)(OTF)](2+) (D1-OTF)
      makes it possible for this to be reduced by 2 equiv of Fc* via a two-step
      electron-transfer sequence. Reactions of the fully reduced complex
      [Cu(I)(2)(LO)](+) (D3) with O(2) in the presence of HOTF led to the low
      temperature detection of the absorption spectra due to the peroxo complex
      [Cu(II)(2)(LO)(OO)] (D) and the protonated hydroperoxo complex
      [Cu(II)(2)(LO)(OOH)](2+) (D4). No further Fc* reduction of D4 occurs, and it is
      instead further protonated by HOTF to yield H(2)O(2) accompanied by regeneration
      of [Cu(II)(2)(LO)(OTF)](2+) (D1-OTF), thus completing the catalytic cycle for the
      two-electron reduction of O(2) by Fc*. Kinetic studies on the formation of Fc*(+)
      under catalytic conditions as well as for separate examination of the electron
      transfer from Fc* to D1-OTF reveal there are two important reaction pathways
      operating. One is a rate-determining second reduction of D1-OTF, thus electron
      transfer from Fc* to a mixed-valent intermediate [Cu(II)Cu(I)(LO)](2+) (D2),
      which leads to [Cu(I)(2)(LO)](+) that is coupled with O(2) binding to produce
      [Cu(II)(2)(LO)(OO)](+) (D). The other involves direct reaction of O(2) with the
      mixed-valent compound D2 followed by rapid Fc* reduction of a putative superoxo
      dicopper(II) species thus formed, producing D.

PMID- 22462523
TI  - Scanned carbon beam irradiation of moving films: comparison of measured and
      calculated response.
AB  - BACKGROUND: Treatment of moving target volumes with scanned particle beams
      benefits from treatment planning that includes the time domain (4D). Part of 4D
      treatment planning is calculation of the expected result. These calculation codes
      should be verified against suitable measurements. We performed simulations and
      measurements to validate calculation of the film response in the presence of
      target motion. METHODS: All calculations were performed with GSI's treatment
      planning system TRiP. Interplay patterns between scanned particle beams and
      moving film detectors are very sensitive to slight deviations of the assumed
      motion parameters and therefore ideally suited to validate 4D calculations. In
      total, 14 film motion parameter combinations with lateral motion amplitudes of 8,
      15, and 20 mm and 4 combinations for lateral motion including range changes were
      used. Experimental and calculated film responses were compared by relative
      difference, mean deviation in two regions-of-interest, as well as line profiles.
      RESULTS: Irradiations of stationary films resulted in a mean relative difference
      of -1.52% +/- 2.06% of measured and calculated responses. In comparison to this
      reference result, measurements with translational film motion resulted in a mean
      difference of -0.92% +/- 1.30%. In case of irradiations incorporating range
      changes with a stack of 5 films as detector the deviations increased to -6.4 +/-
      2.6% (-10.3 +/- 9.0% if film in distal fall-off is included) in comparison to 
      3.6% +/- 2.5% (-13.5% +/- 19.9% including the distal film) for the stationary
      irradiation. Furthermore, the comparison of line profiles of 4D calculations and
      experimental data showed only slight deviations at the borders of the irradiated
      area. The comparisons of pure lateral motion were used to determine the number of
      motion states that are required for 4D calculations depending on the motion
      amplitude. 6 motion states per 10 mm motion amplitude are sufficient to calculate
      the film response in the presence of motion. CONCLUSIONS: By comparison to
      experimental data, the 4D extension of GSI's treatment planning system TRiP has
      been successfully validated for film response calculations in the presence of
      target motion within the accuracy limitation given by film-based dosimetry.

PMID- 22462524
TI  - Evolutionary stasis in Euphorbiaceae pollen: selection and constraints.
AB  - Although much attention has been paid to the role of stabilizing selection,
      empirical analyses testing the role of developmental constraints in evolutionary
      stasis remain rare, particularly for plants. This topic is studied here with a
      focus on the evolution of a pollen ontogenetic feature, the last points of
      callose deposition (LPCD) pattern, involved in the determination of an adaptive
      morphological pollen character (aperture pattern). The LPCD pattern exhibits a
      low level of evolution in eudicots, as compared to the evolution observed in
      monocots. Stasis in this pattern might be explained by developmental constraints
      expressed during male meiosis (microsporogenesis) or by selective pressures
      expressed through the adaptive role of the aperture pattern. Here, we demonstrate
      that the LPCD pattern is conserved in Euphorbiaceae s.s. and that this
      conservatism is primarily due to selective pressures. A phylogenetic association
      was found between the putative removal of selective pressures on pollen
      morphology after the origin of inaperturate pollen, and the appearance of
      variation in microsporogenesis and in the resulting LPCD pattern, suggesting that
      stasis was due to these selective pressures. However, even in a neutral context,
      variation in microsporogenesis was biased. This should therefore favour the
      appearance of some developmental and morphological phenotypes rather than others.

PMID- 22462526
TI  - Longitudinal trends in use and costs of prescription medication in patients with
      type 1 diabetes: the impact of renal disease.
AB  - OBJECTIVE: We estimated trends in prescription medication costs in out-patients
      with type 1 diabetes by various stages of diabetic nephropathy (DN), before the
      development of end-stage renal disease, between 1995 and 2005. METHODS: Patients
      with normo- (n = 1,334), micro- (n = 206), and macroalbuminuria (n = 365) were
      identified from the Finnish Diabetic Nephropathy (FinnDiane) database. All
      purchases of medications were obtained from the Drug Prescription Register.
      RESULTS: The costs levels differed significantly (P < 0.0001) between all groups.
      The estimated annual costs per patient in 1995 were ?1,310 (95% CI 1,230-1,400),
      ?1,450 (1,300-1,600), and ?1,770 (1,620-1,930) in the normo-, micro-, and
      macroalbuminuria groups, respectively. The corresponding costs in 2005 were
      ?1,950 (1,830-2,080), ?2,110 (1,910-2,320), and ?2,900 (2,650-3,180). The costs
      increased in all groups over time (P < 0.0001). The annual average increase was
      3.5%, 3.3%, and 5.2% in each group. After the generic substitution was
      introduced, the costs of agents acting on the renin- angiotensin system and lipid
      modifying agents dropped, although the number of users increased at the same
      time. CONCLUSIONS: More severe stages of DN have a substantial impact on the
      costs, which suggests that early prevention and intensive treatment of renal
      disease may generate remarkable annual cost savings.

PMID- 22462525
TI  - Cognitive deficits following exposure to pneumococcal meningitis: an event
      related potential study.
AB  - BACKGROUND: Pneumococcal meningitis (PM) is a severe and life-threatening disease
      that is associated with cognitive impairment including learning difficulties,
      cognitive slowness, short-term memory deficits and poor academic performance.
      There are limited data on cognitive outcomes following exposure to PM from Africa
      mainly due to lack of culturally appropriate tools. We report cognitive processes
      of exposed children as measured by auditory and visual event-related potentials.
      METHODS: Sixty-five children (32 male, mean 8.4 years, SD 3.0 years) aged between
      4-15 years with a history of PM and an age-matched control group of 93 children
      (46 male; mean 8.4 years, SD 2.7 years) were recruited from a well-demarcated
      study area in Kilifi. In the present study, both baseline to peak and peak-to
      peak amplitude differences are reported. RESULTS: Children with a history of
      pneumococcal meningitis had significantly longer auditory P1 and P3a latencies
      and smaller P1 amplitudes compared to unexposed children. In the visual paradigm,
      children with PM seemingly lacked a novelty P3a component around 350 ms where
      control children had a maximum, and showed a lack of stimulus differentiation at
      Nc. Further, children with exposure to PM had smaller peak to peak amplitude (N2
      P1) compared to unexposed children. CONCLUSION: The results suggest that children
      with a history of PM process novelty differently than do unexposed children, with
      slower latencies and reduced or absent components. This pattern suggests poorer
      auditory attention and/or cognitive slowness and poorer visual attention
      orienting, possibly due to disruption in the functions of the lateral prefrontal
      and superior temporal cortices. ERPs may be useful for assessment of the
      development of perceptual-cognitive functions in post brain-injury in African
      children by providing an alternate way of assessing cognitive development in
      patient groups for whom more typical standardized neuropsychological assessments
      are unavailable.

PMID- 22462527
TI  - Immediate supracrestal implant placement with immediate temporization in the
      anterior dentition: a retrospective study of 31 implants in 26 patients with up
      to 5.5-years follow-up.
AB  - AIM: To assess the stability of the peri-implant bone, the peri-implant soft
      tissues and the esthetic success of immediately placed implants. MATERIALS AND
      METHODS: In this retrospective study, scalloped-shaped implants were placed
      immediately and 1.5 mm supracrestally after single-tooth extraction. All implants
      were immediately restored with an implant-supported temporary crown. Clinical and
      radiographic parameters were assessed on the day of tooth extraction with
      subsequent implant placement and temporization, after 6 months at delivery of the
      final crown, and after 1, after 3, and up to 5 years after crown delivery.
      RESULTS: All 31 implants were clinically successful and in function during the
      observation period (mean 3.4 years). The peri-implant soft tissues were
      clinically healthy as indicated by a low mean plaque (below 0.5) and sulcus
      bleeding index (below 0.24) values. The distance between the implant shoulder and
      the first visible bone-to-implant contact (DIBrx) was measured at the mesial and
      distal aspects of each implant using periapical radiographs. Mean values for
      DIBrx of 1.73 +/- 0.59 mm directly after implant placement and 2.25 +/- 0.66 mm
      after the observation period demonstrated stable peri-implant bone levels. The
      mean distance from the implant shoulder to the gingival margin on the labial
      aspect (DIM vestibular) was 2.21 +/- 1.09 mm directly after implant placement.
      Respective values at 1 year, at 3 years and at 5 years after crown delivery
      remained stable thus demonstrating little if any gingival recession. The assessed
      mean values for the pink (PES) and white (WES) esthetic score (0 = 0-33% score, 1
      = 34-66% score, 2 = 67-100% score) were 8/4 directly after implant placement and
      9/10 after 1.5-5.5 years of observation. CONCLUSIONS: After an observation time
      of 1.5-5.5 years all implants demonstrated very stable soft tissue levels with
      little if any recession on mesial, distal and labial aspects and an esthetic
      score that was reasonable directly after temporization and developed toward
      maximum scores over time.

PMID- 22462528
TI  - Worry vs. knowledge about treatment-associated hypoglycaemia and weight gain in
      type 2 diabetic patients on metformin and/or sulphonylurea.
AB  - BACKGROUND AND AIMS: Hypoglycaemia and body weight gain are side effects of
      certain glucose-lowering drugs, e.g. sulphonylurea (SU) compounds. Type 2
      diabetes mellitus (T2DM) is often treated with multiple oral antidiabetic drugs
      complicating patient insight into drug safety and side effects. We aimed to
      elucidate the extent of patient worry about hypoglycaemia and body weight gain
      contra their knowledge about these two phenomena being actual side effects of SU.
      METHODS: We used an observational, cross-sectional approach and included 492
      patients with T2DM: 331 (67%) on metformin alone (MET), 52 (11%) on SU in
      monotherapy (SU), and 109 (22%) on metformin in combination with SU (MET + SU).
      All participants filled in a questionnaire enquiring about the patient's
      knowledge and worry about side effects such as hypoglycaemia and weight gain in
      addition to the importance of their treatment not eliciting these two side
      effects. RESULTS: Nineteen (MET), 29 (SU) and 38% (MET + SU) of the patients in
      the three groups agreed (fully or partially) with the statement 'treatment with
      my diabetes medicine increases the risk of episodes with low blood sugar'.
      Significantly (p < 0.001) larger proportions of the three groups (68, 75 and 68%)
      felt it important that their glucose-lowering medication did not increase the
      risk of hypoglycaemia. Similar discrepancies for weight gain were observed.
      LIMITATIONS: The present study has several limitations: patients consisted of a
      non-randomised cohort, data were patient-reported and only patients with internet
      access could participate. CONCLUSION: A considerable proportion of patients with
      T2DM treated with SU are not aware of the risks of hypoglycaemia and weight gain
      associated with the treatment. This information gap exists despite the fact that
      to most patients treated with SU it is important that their antidiabetic
      treatment does not cause hypoglycaemia and/or weight gain, suggesting that these
      patients might be insufficiently informed about side effects.

PMID- 22462529
TI  - Accuracy of perception of ovulation day in women trying to conceive.
AB  - BACKGROUND: The likelihood of conception is increased if intercourse is timed to
      coincide with the fertile period (5 days up to ovulation). However, to be
      effective, this requires good awareness of the day of ovulation. The aim of this
      study was to examine the accuracy of women's perceived ovulation day, compared
      with actual fertile days, in a cohort of women trying to conceive. MAIN OUTCOME
      MEASURES: Comparison of women's estimated day of ovulation with their actual
      ovulation day (determined by detecting luteinising hormone). METHODS: This was a
      sample collection study and volunteer women were recruited via online
      advertising. At recruitment volunteers reported the cycle day they believed they
      ovulated. They then used a home urine fertility monitor to test their daily
      fertility status to time intercourse to try and achieve conception, in addition
      to collecting early morning urine samples for laboratory analysis. The main
      outcome measure was a comparison of women's estimated day of ovulation with their
      actual ovulation day, as determined by urine detection of luteinising hormone.
      RESULTS: Three hundred and thirty women were recruited onto the study and data
      was available for 102 volunteers who became pregnant. Thirteen women (12.7%)
      correctly estimated their ovulation day; median difference +2 days, range -10 to
      +27 days. The most common days for estimation of ovulation were day 14 (35.5%)
      and day 15 (15.7%). Only 55% of estimated ovulation days fell within the
      volunteers' fertile window; only 27% on days of peak fertility. CONCLUSIONS:
      Women trying to conceive may benefit from using a prospective method to identify
      their fertile phase, as a significant proportion could be incorrectly estimating
      their fertile days. These observations were made on women who were actively
      looking for knowledge on fertility and considered only cycles where conception
      occurred, inaccuracy could be greater if a broader population is considered.

PMID- 22462530
TI  - Annualized relapse rate of first-line treatments for multiple sclerosis: a meta
      analysis, including indirect comparisons versus fingolimod.
AB  - OBJECTIVES: Previous systematic reviews and meta-analyses of treatments in
      relapsing-remitting multiple sclerosis (RRMS) derived their findings from either
      placebo-controlled studies only or separately from head-to-head and comparative
      studies. The purpose of this study is to compare annualized relapse rates (ARR)
      of fingolimod versus all of the commonly used first-line treatments in RRMS using
      evidence from both placebo-controlled and head-to-head studies. In absence of the
      head-to-head data between fingolimod and the other treatments, these comparisons
      were formed using meta-analysis techniques for indirect treatment comparisons.
      METHODS: A systematic literature review was conducted by searching MEDLINE,
      EMBASE, and the Cochrane Library with no limitations applied on publication
      language or dates. Included studies were randomized controlled trials evaluating
      one or more of fingolimod, interferon beta-1a, interferon beta-1b, or glatiramer
      acetate in RRMS populations. Primary outcome was ARR. Data extraction included
      author, year, treatment, dosage, mean age, percentage females, duration of
      disease, Expanded Disability Status Scale (EDSS) score at baseline, relapses in 2
      years prior to baseline, trial duration, relapse-related outcome, and definition
      of relapse. The indirect treatment comparisons were performed using a mixed
      treatment comparison framework. ARR was analyzed as a Poisson outcome. RESULTS:
      The relative ARRs, for each treatment versus fingolimod, estimated from our meta
      analyses were 1.43 (glatiramer acetate 20 mg), 1.51 (interferon beta-1b 250 mcg),
      1.55 (interferon beta-1a 44 mcg), 1.67 (interferon beta-1a 22 mcg), 1.93
      (interferon beta-1a 30 mcg), and 2.32 (placebo). None of the 95% confidence
      intervals for these estimates overlapped unity, implying statistical significance
      of these findings. LIMITATIONS: The key limitations of this study are the
      persisting heterogeneity even after adjusting for covariates and the variability
      in outcome definition across the included trials. CONCLUSIONS: Our study
      demonstrated that fingolimod significantly reduces relapse frequency in patients
      with RRMS compared with current first-line disease-modifying therapies.

PMID- 22462531
TI  - A systematic review and meta-analysis of randomized controlled trials comparing
      pioglitazone versus metformin in the treatment of polycystic ovary syndrome.
AB  - OBJECTIVE: Evidence indicates that metformin and pioglitazone both improve
      insulin resistance and hirsutism among patient with polycystic ovarian syndrome
      (PCOS). However, the effectiveness of pioglitazone versus metformin in the
      treatment of PCOS remains controversial. To summarize the relative efficacy of
      pioglitazone and metformin in PCOS patients, a systematic review and meta
      analysis of randomized controlled trials (RCTs) was performed. METHODS: The
      authors searched MEDLINE, EMBASE, CNKI and WANFANG DATA for articles published up
      to November 2011 to identify those comparing pioglitazone versus metformin as a
      treatment for PCOS. RESULTS: Of the 161 studies retrieved, six trials were
      included in this analysis, including a total of 278 women with PCOS. Pioglitazone
      was found to be significantly more effective than metformin at reducing fasting
      insulin level (P = 0.002, standardized mean differences [SMD] = -0.37, 95%
      confidence interval [CI] [-0.61, -0.13]). Similarly, pioglitazone was found to be
      significantly more effective than metformin at improving the HOMA-IR index (P =
      0.014, SMD = -0.32, 95% CI [-0.57, -0.06]). However, pioglitazone was
      significantly less effective than metformin at reducing body mass index (BMI; P =
      0.038, SMD = 0.25, 95% CI [0.01, 0.49]). The effect of pioglitazone on fasting
      glucose levels, testosterone levels, and Ferriman-Gallwey scores was not
      significantly different from that of metformin (P greater than 0.05 for all).
      CONCLUSION: This systematic review and meta-analysis suggests that pioglitazone
      was more suitable for treating hyperinsulinemia and insulin resistance among PCOS
      patients, while metformin was more effective in reducing body weight. Well
      designed RCTs are needed to provide better evidence.

PMID- 22462532
TI  - In situ imaging highlights local structural changes during heating: the case of
      meat.
AB  - Understanding and monitoring deformation and water content changes in meat during
      cooking is of prime importance. We show the possibilities offered by nuclear
      magnetic resonance imaging (MRI) for the in situ dynamic measurement of
      deformation fields and water content mapping during beef heating from 20 to 75 
      degrees C. MRIs were acquired during heating, and image registration was used to
      calculate the deformation field. The temperature distribution in the sample was
      simulated numerically to link structural modifications and water transfer to
      temperature values. During heating, proton density decreases because of a
      magnetic susceptibility drop with temperature and water expulsion due to muscle
      contraction. A positive relationship was found between local cumulative
      deformation and water content. This new approach makes it possible to identify
      the deformation field and water transfer simultaneously and to trace thermal
      history to build heuristic models linking these parameters.

PMID- 22462533
TI  - Fibroblast growth factor 23 in hypophosphataemic HIV-positive adults on
      tenofovir.
AB  - OBJECTIVES: Hypophosphataemia is common in HIV-positive patients, in particular
      in those using tenofovir disoproxil fumarate (TDF). Its pathogenesis is not well
      understood. The importance of fibroblast growth factor 23 (FGF-23), the most
      potent phosphaturic hormone known today, has not been studied in these patients.
      The aim of the study was to investigate whether FGF-23 might be involved in the
      aetiology of hypophosphataemia in HIV-positive patients on tenofovir. METHODS:
      Calcium and phosphate metabolism was studied in 36 HIV-positive patients on TDF.
      Hypophosphataemia was defined as a serum phosphate level<0.75 mmol/L. RESULTS:
      Fifteen patients (42%) had hypophosphataemia (group 1), and 21 had a normal serum
      phosphate level (group 2). The renal phosphate reabsorption threshold [tubular
      maximum phosphate reabsorption per glomerular filtration rate (TmP/gfr)] was
      significantly lower in group 1 than in group 2 (0.58 +/- 0.04 vs. 0.91 +/- 0.03
      mmol/L, respectively; P<0.0001). The serum phosphate concentration was strongly
      correlated with TmP/gfr (R=0.71; P<0.0001). Both groups had normal serum FGF-23
      levels, and serum phosphate and TmP/gfr were not related to serum parathyroid
      hormone (PTH) or FGF-23 levels. CONCLUSION: FGF-23 is not involved in the
      pathogenesis of hypophosphataemia in HIV-positive patients on TDF. The data
      suggest that a PTH-like factor may be involved.

PMID- 22462534
TI  - First ruthenium(II) polypyridyl complex as a true molecular "light switch" for
      triplex RNA structure: [Ru(phen)2(mdpz)]2+ enhances the stability of
      Poly(U).Poly(A)*Poly(U).
AB  - Stabilization of triple helical structures is extremely important for carrying
      out their biological  functions. Nucleic acid triple helices may be formed with
      DNA or RNA strands. In contrast to many studies in DNA, little has been reported
      concerning the recognition of the RNA triplex by transition-metal complexes. In
      this article, [Ru(phen)(2)(mdpz)](2+) (Ru1) is the first metal complex able to
      enhance the stability of the RNA triplex Poly(U).Poly(A)*Poly(U) and serve as a
      prominent molecular "light switch" for the RNA triplex.

PMID- 22462535
TI  - ROCK1 and ROCK2 regulate epithelial polarisation and geometric cell shape.
AB  - BACKGROUND INFORMATION: Cell-cell adhesion and contraction play an essential role
      in the maintenance of geometric shape and polarisation of epithelial cells.
      However, the molecular regulation of contraction during cell elongation leading
      to epithelial polarisation and acquisition of geometric cell shape is not clear.
      RESULTS: Upon induction of cell-cell adhesion, we find that human keratinocytes
      acquire specific geometric shapes favouring hexagons, by re-modelling junction
      length/orientation and thus neighbour allocation. Acquisition of geometric shape
      correlates temporally with epithelial polarisation, as shown by an increase in
      lateral height. ROCK1 and ROCK2 are important regulators of myosin II
      contraction, but their specific role in epithelial cell shape has not been
      addressed. Depletion of ROCK proteins interferes with the correct proportion of
      hexagonal cell shapes and full elongation of lateral domain. Interestingly, ROCK
      proteins are not essential for maintenance of circumferential thin bundles, the
      main contractile epithelial F-actin pool. Instead, ROCK1 or ROCK2 regulates thin
      bundle contraction and positioning along the lateral domain, an important event
      for the stabilisation of the elongating lateral domain. Mechanistically, E
      cadherin clustering specifically leads to ROCK1/ROCK2-dependent inactivation of
      myosin phosphatase and phosphorylation of myosin regulatory light chain. These
      events correlate temporally with the increase in lateral height and thin bundle
      compaction towards junctions. CONCLUSION: We conclude that ROCK proteins are
      necessary for acquisition of elongated and geometric cell shape, two key events
      for epithelial differentiation.

PMID- 22462536
TI  - Eosin Y triplet state as a probe of spatial heterogeneity in microcrystalline
      cellulose.
AB  - The photophysical behavior of eosin Y adsorbed onto microcrystalline cellulose
      was evaluated by reflectance spectroscopy, steady-state fluorescence spectroscopy
      and laser induced time-resolved luminescence. On increasing the concentration of
      the dye, small changes in absorption spectra, fluorescence redshifts and
      fluorescence quenching are observed. Changes in absorption spectra point to the
      occurrence of weak exciton interactions among close-lying dye molecules, whereas
      fluorescence is affected by reabsorption and excitation energy trapping.
      Phosphorescence decays are concentration independent as a result of the
      negligible exciton interaction of dye pairs in the triplet state. Lifetime
      distribution and bilinear regression analyses of time-resolved phosphorescence
      and delayed fluorescence spectra reveal the existence of two different
      environments: long-lived, more energetic triplet states arise from dyes tightly
      entrapped within the cellulose chains, while short-lived, less-energetic states
      result from dyes in more flexible environments. Stronger hydrogen bond
      interactions between the dye and cellulose hydroxyl groups lead in the latter
      case to a lower triplet energy and faster radiationless decay. These effects,
      observed also at low temperatures, are similar to those encountered in several
      amorphous systems, but rather than being originated in changes in the environment
      during the triplet lifetime, they are ascribed in this case to spatial
      heterogeneity.

PMID- 22462537
TI  - Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome.
AB  - CHARGE (coloboma of the eye, heart defects, choanal atresia, retarded growth and
      development, genital hypoplasia and ear anomalies and/or hearing loss) syndrome
      is a rare genetic, multiple-malformation syndrome. About 80% of patients with a
      clinical diagnose, have a mutation or a deletion in the gene encoding
      chromodomain helicase DNA-binding protein 7 (CHD7). Genotype-phenotype
      correlation is only partly known. In this nationwide study, phenotypic
      characteristics of 18 Danish CHD7 mutation positive CHARGE individuals (N = 18)
      are presented. We studied patient records, clinical photographs, computed
      tomography, and magnetic resonance imaging (MRI). Information was not available
      for all traits in all subjects. Therefore, the results are presented as
      fractions. The following prevalence of cardinal symptoms were found: coloboma,
      16/17; heart defects, 14/18; choanal atresia, 7/17; retarded growth and
      development, 11/13; genital abnormalities, 5/18; ear anomalies, 15/17 and
      sensorineural hearing loss, 14/15. Vestibular dysfunction (10/13) and swallowing
      problems (12/15) were other frequent cranial nerve dysfunctions. Three
      dimensional reconstructions of MRI scans showed temporal bone abnormalities in
      >85%. CHARGE syndrome present a broad phenotypic spectrum, although some clinical
      features are more frequently occurring than others. Here, we suggest that genetic
      testing for CHD7 mutation should be considered in neonates with a specific
      combination of several clinical symptoms.

PMID- 22462539
TI  - Photoreactive azido-containing silica nanoparticle/polycation multilayers:
      durable superhydrophobic coating on cotton fabrics.
AB  - In this study, we report the functionalization of silica nanoparticles with
      highly photoreactive phenyl azido groups and their utility as a negatively
      charged building block for layer-by-layer (LbL) electrostatic assembly to produce
      a stable silica nanoparticle coating. Azido-terminated silica nanoparticles were
      prepared by the functionalization of bare silica nanoparticles with 3
      aminopropyltrimethoxysilane followed by the reaction with 4-azidobenzoic acid.
      The azido functionalization was confirmed by FTIR and XPS. Poly(allylamine
      hydrochloride) was also grafted with phenyl azido groups and used as
      photoreactive polycations for LbL assembly. For the photoreactive silica
      nanoparticle/polycation multilayers, UV irradiation can induce the covalent cross
      linking within the multilayers as well as the anchoring of the multilayer film
      onto the organic substrate, through azido photochemical reactions including C-H
      insertion/abstraction reactions with surrounding molecules and dimerization of
      azido groups. Our results show that the stability of the silica
      nanoparticle/polycation multilayer film was greatly improved after UV
      irradiation. Combined with a fluoroalkylsilane post-treatment, the photoreactive
      LbL multilayers were used as a coating for superhydrophobic modification of
      cotton fabrics. Herein the LbL assembly method enables us to tailor the number of
      the coated silica nanoparticles through the assembly cycles. The
      superhydrophobicity of cotton fabrics was durable against acids, bases, and
      organic solvents, as well as repeated machine wash. Because of the unique azido
      photochemistry, the approach used here to anchor silica nanoparticles is
      applicable to almost any organic substrate.

PMID- 22462538
TI  - A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma
      resistance to an oncolytic adenovirus.
AB  - The homing properties of mesenchymal stromal cells (MSCs) toward tumors turn them
      into attractive tools for combining cell and gene therapy. The aim of this study
      was to select in a feasible way a human bone marrow-derived MSC subpopulation
      that might exhibit a selective ability to target the tumor mass. Using
      differential in vitro adhesive capacities during cells isolation, we selected a
      specific MSC subpopulation (termed MO-MSCs) that exhibited enhanced multipotent
      capacity and increased cell surface expression of specific integrins (integrins
      alpha2, alpha3, and alpha5), which correlated with an enhanced MO-MSCs
      adhesiveness toward their specific ligands. Moreover, MO-MSCs exhibited a higher
      migration toward conditioned media from different cancer cell lines and fresh
      human breast cancer samples in the presence or not of a human microendothelium
      monolayer. Further in vivo studies demonstrated increased tumor homing of MO-MSCs
      toward established 578T and MD-MBA-231 breast cancer and A375N melanoma tumor
      xenografts. Tumor penetration by MO-MSCs was highly dependent on
      metallopeptidases production as it was inhibited by the specific inhibitor 1,10
      phenantroline. Finally, systemically administered MO-MSCs preloaded with an
      oncolytic adenovirus significantly inhibited tumor growth in mice harboring
      established A375N melanomas, overcoming the natural resistance of the tumor to in
      situ administration of the oncolytic adenovirus. In summary, this work
      characterizes a novel MSC subpopulation with increased tumor homing capacity that
      can be used to transport therapeutic compounds.

PMID- 22462540
TI  - Subtype-dependent postnatal development of taste receptor cells in mouse
      fungiform taste buds.
AB  - Taste buds contain two types of taste receptor cells, inositol 1,4,5-triphosphate
      receptor type 3-immunoreactive cells (type II cells) and synaptosomal-associating
      protein-25-immunoreactive cells (type III cells). We investigated their postnatal
      development in mouse fungiform taste buds immunohistochemically and
      electrophysiologically. The cell density, i.e. the number of cells per taste bud
      divided by the maximal area of the horizontal cross-section of the taste bud, of
      type II cells increased by postnatal day (PD)49, where as that of type III cells
      was unchanged throughout the postnatal observation period and was equal to that
      of the adult cells at PD1. The immunoreactivity of taste bud cell subtypes was
      the same as that of their respective subtypes in adult mice throughout the
      postnatal observation period. Almost all type II cells were immunoreactive to
      gustducin at PD1, and then the ratio of gustducin-immunoreactive type II cells to
      all type II cells decreased to a saturation level, ~60% of all type II cells, by
      PD15. Type II and III cells generated voltage-gated currents similar to their
      respective adult cells even at PD3. These results show that infant taste receptor
      cells are as excitable as those of adults and propagate in a subtype-dependent
      manner. The relationship between the ratio of each taste receptor cell subtype to
      all cells and taste nerve responses are discussed.

PMID- 22462541
TI  - What is the brain-cancer connection?
AB  - A focus of much cancer research is at the molecular and cellular levels. In
      contrast, the effects of social interactions and psychological state are less
      investigated, and considered by many a "soft" science. Yet several highly
      rigorous studies have begun to tease out biochemical pathways by which the brain
      can influence the development and growth of cancer. Previous reviews have
      discussed the concept of stress and cancer. Here, we discuss recent work showing
      environments that are more complex and challenging, but not stressful per se, and
      that have robust effects on peripheral cancer by activating a specific
      neuroendocrine brain-adipocyte axis. These enriched environments lead to
      activation of the sympathetic innervation of fat tissue, suppression of leptin,
      and a reduction in cancer proliferation by inducing hypothalamic BDNF expression.
      We summarize this work and discuss how these data integrate into the body of
      literature regarding stress, the environment, and cancer.

PMID- 22462542
TI  - The role of organizers in patterning the nervous system.
AB  - The foundation for the anatomical and functional complexity of the vertebrate
      central nervous system is laid during embryogenesis. After Spemann's organizer
      and its derivatives have endowed the neural plate with a coarse pattern along its
      anteroposterior and mediolateral axes, this basis is progressively refined by the
      activity of secondary organizers within the neuroepithelium that function by
      releasing diffusible signaling factors. Dorsoventral patterning is mediated by
      two organizer regions that extend along the dorsal and ventral midlines of the
      entire neuraxis, whereas anteroposterior patterning is controlled by several
      discrete organizers. Here we review how these secondary organizers are
      established and how they exert their signaling functions. Organizer signals come
      from a surprisingly limited set of signaling factor families, indicating that the
      competence of target cells to respond to those signals plays an important part in
      neural patterning.

PMID- 22462544
TI  - Critical-period plasticity in the visual cortex.
AB  - In many regions of the developing brain, neuronal circuits undergo defined phases
      of enhanced plasticity, termed critical periods. Work in the rodent visual cortex
      has led to important insights into the cellular and molecular mechanisms
      regulating the timing of the critical period. Although there is little doubt that
      the maturation of specific inhibitory circuits plays a key role in the opening of
      the critical period in the visual cortex, it is less clear what puts an end to
      it. In this review, we describe the established mechanisms and point out where
      more experimental work is needed. We also show that plasticity in the visual
      cortex is present well before, and long after, the peak of the critical period.

PMID- 22462543
TI  - Neural basis of reinforcement learning and decision making.
AB  - Reinforcement learning is an adaptive process in which an animal utilizes its
      previous experience to improve the outcomes of future choices. Computational
      theories of reinforcement learning play a central role in the newly emerging
      areas of neuroeconomics and decision neuroscience. In this framework, actions are
      chosen according to their value functions, which describe how much future reward
      is expected from each action. Value functions can be adjusted not only through
      reward and penalty, but also by the animal's knowledge of its current
      environment. Studies have revealed that a large proportion of the brain is
      involved in representing and updating value functions and using them to choose an
      action. However, how the nature of a behavioral task affects the neural
      mechanisms of reinforcement learning remains incompletely understood. Future
      studies should uncover the principles by which different computational elements
      of reinforcement learning are dynamically coordinated across the entire brain.

PMID- 22462546
TI  - Fingerprint-imprinted polymer: rational selection of peptide epitope templates
      for the determination of proteins by molecularly imprinted polymers.
AB  - The pool of peptides composing a protein allows for its distinctive
      identification in a process named fingerprint (FP) analysis. Here, the FP concept
      is used to develop a method for the rational preparation of molecularly imprinted
      polymers (MIPs) for protein recognition. The fingerprint imprinting (FIP) is
      based on the following: (1) the in silico cleavage of the protein sequence of
      interest with specific agents; (2) the screening of all the peptide sequences
      generated against the UniProtKB database in order to allow for the rational
      selection of distinctive and unique peptides (named as epitopes) of the target
      protein; (3) the selected epitopes are synthesized and used as templates for the
      molecular imprinting process. To prove the principle, NT-proBNP, a marker of the
      risk of cardiovascular events, was chosen as an example. The in silico analysis
      of the NT-proBNP sequence allowed us to individuate the peptide candidates, which
      were next used as templates for the preparation of NT-pro-BNP-specific FIPs and
      tested for their ability to bind the NT-proBNP peptides in complex samples.
      Results indicated an imprinting factor, IF, of ~10, a binding capacity of 0.5-2
      mg/g, and the ability to rebind 40% of the template in a complex sample, composed
      of the whole digests of NT-proBNP.

PMID- 22462545
TI  - Attractor dynamics of spatially correlated neural activity in the limbic system.
AB  - Attractor networks are a popular computational construct used to model different
      brain systems. These networks allow elegant computations that are thought to
      represent a number of aspects of brain function. Although there is good reason to
      believe that the brain displays attractor dynamics, it has proven difficult to
      test experimentally whether any particular attractor architecture resides in any
      particular brain circuit. We review models and experimental evidence for three
      systems in the rat brain that are presumed to be components of the rat's
      navigational and memory system. Head-direction cells have been modeled as a ring
      attractor, grid cells as a plane attractor, and place cells both as a plane
      attractor and as a point attractor. Whereas the models have proven to be
      extremely useful conceptual tools, the experimental evidence in their favor,
      although intriguing, is still mostly circumstantial.

PMID- 22462547
TI  - The development of causal categorization.
AB  - Two experiments examined the impact of causal relations between features on
      categorization in 5- to 6-year-old children and adults. Participants learned
      artificial categories containing instances with causally related features and
      noncausal features. They then selected the most likely category member from a
      series of novel test pairs. Classification patterns and logistic regression were
      used to diagnose the presence of independent effects of causal coherence, causal
      status, and relational centrality. Adult classification was driven primarily by
      coherence when causal links were deterministic (Experiment 1) but showed
      additional influences of causal status when links were probabilistic (Experiment
      2). Children's classification was based primarily on causal coherence in both
      cases. There was no effect of relational centrality in either age group. These
      results suggest that the generative model (Rehder, 2003a) provides a good account
      of causal categorization in children as well as adults.

PMID- 22462548
TI  - The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser358
      in adipocytes.
AB  - SIK2 (salt-inducible kinase 2) is a member of the AMPK (AMP-activated protein
      kinase) family of kinases and is highly expressed in adipocytes. We investigated
      the regulation of SIK2 in adipocytes in response to cellular stimuli with
      relevance for adipocyte function and/or AMPK signalling. None of the treatments,
      including insulin, cAMP inducers or AICAR (5-amino-4-imidazolecarboxamide
      riboside), affected SIK2 activity towards peptide or protein substrates in vitro.
      However, stimulation with the cAMP-elevating agent forskolin and the beta
      adrenergic receptor agonist CL 316,243 resulted in a PKA (protein kinase A)
      dependent phosphorylation and 14-3-3 binding of SIK2. Phosphopeptide mapping of
      SIK2 revealed several sites phosphorylated in response to cAMP induction,
      including Ser(358). Site-directed mutagenesis demonstrated that phosphorylation
      of Ser(358), but not the previously reported PKA site Ser(587), was required for
      14-3-3 binding. Immunocytochemistry illustrated that the localization of
      exogenously expressed SIK2 in HEK (human embryonic kidney)-293 cells was
      exclusively cytosolic and remained unchanged after cAMP elevation. Fractionation
      of adipocytes, however, revealed a significant increase of wild-type, but not
      Ser358Ala, HA (haemagglutinin)-SIK2 in the cytosol and a concomitant decrease in
      a particulate fraction after CL 316,243 treatment. This supports a
      phosphorylation-dependent relocalization in adipocytes. We hypothesize that
      regulation of SIK2 by cAMP could play a role for the critical effects of this
      second messenger on lipid metabolism in adipocytes.

PMID- 22462549
TI  - Protocol for a randomised controlled trial examining the impact of a web-based
      personally controlled health management system on the uptake of influenza
      vaccination rates.
AB  - BACKGROUND: Online social networking and personally controlled health management
      systems (PCHMS) offer a new opportunity for developing innovative interventions
      to prevent diseases of public health concern (e.g., influenza) but there are few
      comparative studies about patterns of use and impact of these systems.
      METHODS/DESIGN: A 2010 CONSORT-compliant randomised controlled trial with a two
      group parallel design will assess the efficacy of a web-based PCHMS called
      Healthy.me in facilitating the uptake of influenza vaccine amongst university
      students and staff. Eligible participants are randomised either to obtain access
      to Healthy.me or a 6-month waitlist. Participants complete pre-study, post-study
      and monthly surveys about their health and utilisation of health services. A post
      study clinical audit will be conducted to validate self-reports about influenza
      vaccination and visits to the university health service due to influenza-like
      illness (ILI) amongst a subset of participants. 600 participants older than 18
      years with monthly access to the Internet and email will be recruited.
      Participants who (i) discontinue the online registration process; (ii) report
      obtaining an influenza vaccination in 2010 before the commencement of the study;
      or (iii) report being influenced by other participants to undertake influenza
      vaccination will be excluded from analysis. The primary outcome measure is the
      number of participants obtaining influenza vaccination during the study.
      Secondary outcome measures include: number of participants (i) experiencing ILI
      symptoms, (ii) absent from or experiencing impairment in work or study due to ILI
      symptoms, (iii) using health services or medications due to ILI symptoms; (iv)
      expressing positive or negative attitudes or experiences towards influenza
      vaccination, via their reasons of receiving (or not receiving) influenza vaccine;
      and (v) their patterns of usage of Healthy.me (e.g., frequency and timing of
      hits, duration of access, uptake of specific functions). DISCUSSION: This study
      will provide new insights about the utility of online social networking and PCHMS
      for public health and health promotion. It will help to assess whether a web
      based PCHMS, with connectivity to a health service provider, containing
      information and self-management tools, can improve the uptake of preventive
      health services amongst university students and staff. TRIAL REGISTRATION:
      ACTRN12610000386033 (Australian New Zealand Clinical Trials Registry).

PMID- 22462550
TI  - Levels of physical activity and sedentary time among 10- to 12-year-old boys and
      girls across 5 European countries using accelerometers: an observational study
      within the ENERGY-project.
AB  - BACKGROUND: The study aim was to objectively assess levels of sedentary time,
      light, moderate and vigorous physical activity (PA) among 10-12 year olds across
      five European countries and to examine differences in sedentary time and PA
      according to gender and country. METHODS: 686 children (mean age = 11.6 +/- 0.8
      years, 53% girls, mean BMI = 19.0 +/- 3.4 kg/m(2)) from Belgium, Greece, Hungary,
      the Netherlands and Switzerland wore Actigraph accelerometers and had at least 2
      weekdays with minimum 10 h-wearing time and 1 weekend day with minimum 8 h
      wearing time. Data were analyzed using multivariate analyses of covariance.
      RESULTS: Girls spent significantly more time sedentary (500 minutes/day) than
      boys (474 minutes/day) and significantly less time in light (267 minutes/day) and
      moderate-to-vigorous PA (32 minutes/day) than boys (284 minutes/day; 43
      minutes/day respectively; p < 0.001). 4.6% of the girls and 16.8% of the boys met
      moderate-to-vigorous PA recommendations of at least 60 minutes/day. Greek boys
      were more sedentary (510 minutes/day; all at p < 0.05) than other boys. Dutch
      girls were less sedentary (457 minutes/day; all at p < 0.05) than other girls.
      Swiss girls displayed more moderate-to-vigorous PA (43 minutes/day; at p < 0.05)
      than other girls. CONCLUSIONS: Large proportions of children across different
      European countries did not meet PA recommendations and spent a lot of time
      sedentary. Mean time spent in moderate-to-vigorous PA was significantly lower
      than the recommended 60 minutes. Obesity prevention programmes focusing on both
      decreasing sedentary time and increasing light, moderate and vigorous PA are
      needed for European children, particularly girls.

PMID- 22462551
TI  - Molecular and morphological aspects of annealing-induced stabilization of starch
      crystallites.
AB  - A unique series of potato (mutant) starches with highly different
      amylopectin/amylose (AP/AM) ratios was annealed in excess water at stepwise
      increasing temperatures to increase the starch melting (or gelatinization)
      temperatures in aqueous suspensions. Small-angle X-ray scattering (SAXS)
      experiments revealed that the lamellar starch crystals gain stability upon
      annealing via thickening for high-AM starch, whereas the crystal surface energy
      decreases for AM-free starch. In starches with intermediate AP/AM ratio, both
      mechanisms occur, but the surface energy reduction mechanism prevails. Crystal
      thickening seems to be associated with the cocrystallization of AM with AP,
      leading to very disordered nanomorphologies for which a new SAXS data
      interpretation scheme needed to be developed. Annealing affects neither the
      crystal internal structure nor the spherulitic morphology on a micrometer length
      scale.

PMID- 22462552
TI  - Relationship between the nutritional status of breastfeeding Mayan mothers and
      their infants in Guatemala.
AB  - A case-control study was conducted to determine the association between maternal
      height and infant length-for-age, and to evaluate how this association is
      modified by either maternal or infant nutritional status. We hypothesised that
      maternal excess caloric intake [measured as body mass index (BMI)] would increase
      the association, while infant nutrition (measured in main meals consumed in
      addition to breastfeeding) will diminish the effect. Mother and infant pairs in
      Chimaltenango, Guatemala, were measured for anthropometric values and nutritional
      status, and mothers were interviewed to elicit nutritional and socio-economic
      information. Infant length was converted into z-scores based on the World Health
      Organization's (WHO) standards. Odds ratios (ORs), associated 95% confidence
      intervals (CIs) and the relative excess risk due to interaction (RERI) were
      calculated. Cases were infants below 2 z-scores of the WHO's length-for-age,
      while controls were infants within the -2 to 2 z-score range. Cases (n = 84) had
      an increased odds (OR: 3.00, 95% CI: 1.57-5.74) of being born to a stunted mother
      (below 145 cm) when compared with controls (n = 85). When adjusted for potential
      confounders, the OR decreased to 2.55 (95% CI: 1.30-5.02). Negative RERI values
      were produced for the joint exposure of maternal BMI >= 25 and maternal
      stuntedness (RERI: -0.96), as well as for the joint exposure of maternal
      stuntedness and infant nutrition (RERI: -2.27). Our results confirm that maternal
      stuntedness is a significant contributor to infant stuntedness; however, this
      association is modified negligibly by maternal nutritional status and
      significantly by infant nutritional status, each in a protective manner.

PMID- 22462554
TI  - Facile synthesis of Ag interlayer doped graphene by chemical vapor deposition
      using polystyrene as solid carbon source.
AB  - Graphene was synthesized by chemical vapor deposition using polystyrene as the
      solid carbon source. The number of graphene layers could be controlled by
      regulating the weight of polystyrene under atmospheric pressure at 1000  degrees
      C. Silver nanoparticles were then deposited on the graphene by a citrate
      reduction method. The interaction between graphene and silver was investigated by
      suface-enhanced Raman scattering spectra and X-ray photoelectron spectroscopy.
      The change in the G band position indicates n-type doping of the graphene due to
      an interaction between the silver and the graphene. Silver interlayer doped four
      layer graphene shows a sheet resistance of 63 Omega/sq and a light transmittance
      of 85.4% at 550 nm. The optical and electrical quality of graphene exceeds the
      minimum industry standard for indium tin oxide replacement materials. It is
      clearly understood that the environmental sheet resistance stability of the
      interlayer doped graphene film is better than that of surface doped graphene
      sheets. The presence of graphene at the surface also acts as a protective layer
      for the inner silver ions and clusters.

PMID- 22462555
TI  - Structural Changes in Cobalt(II) Complexes Resulting from Nonsteric Substutent
      Effects with Potentially Five-Coordinate Ligands.

PMID- 22462553
TI  - STI571 reduces TRAIL-induced apoptosis in colon cancer cells: c-Abl activation by
      the death receptor leads to stress kinase-dependent cell death.
AB  - BACKGROUND: In an effort to achieve better cancer therapies, we elucidated the
      combination cancer therapy of STI571 (an inhibitor of Bcr-Abl and clinically used
      for chronic myelogenous leukemia) and TNF-related apoptosis-inducing ligand
      (TRAIL, a developing antitumor agent) in leukemia, colon, and prostate cancer
      cells. METHODS: Colon cancer (HCT116, SW480), prostate cancer (PC3, LNCaP) and
      leukemia (K562) cells were treated with STI571 and TRAIL. Cell viability was
      determined by MTT assay and sub-G1 appearance. Protein expression and kinase
      phosphorylation were determined by Western blotting. c-Abl and p73 activities
      were inhibited by target-specific small interfering (si)RNA. In vitro kinase
      assay of c-Abl was conducted using CRK as a substrate. RESULTS: We found that
      STI571 exerts opposite effects on the antitumor activity of TRAIL. It enhanced
      cytotoxicity in TRAIL-treated K562 leukemia cells and reduced TRAIL-induced
      apoptosis in HCT116 and SW480 colon cancer cells, while having no effect on PC3
      and LNCaP cells. In colon and prostate cancer cells, TRAIL caused c-Abl cleavage
      to the active form via a caspase pathway. Interestingly, JNK and p38 MAPK
      inhibitors effectively blocked TRAIL-induced toxicity in the colon, but not in
      prostate cancer cells. Next, we found that STI571 could attenuate TRAIL-induced c
      Abl, JNK and p38 activation in HCT116 cells. In addition, siRNA targeting
      knockdown of c-Abl and p73 also reduced TRAIL-induced cytotoxicity, rendering
      HCT116 cells less responsive to stress kinase activation, and masking the
      cytoprotective effect of STI571. CONCLUSIONS: All together we demonstrate a novel
      mediator role of p73 in activating the stress kinases p38 and JNK in the
      classical apoptotic pathway of TRAIL. TRAIL via caspase-dependent action can
      sequentially activate c-Abl, p73, and stress kinases, which contribute to
      apoptosis in colon cancer cells. Through the inhibition of c-Abl-mediated
      apoptotic p73 signaling, STI571 reduces the antitumor activity of TRAIL in colon
      cancer cells. Our results raise additional concerns when developing combination
      cancer therapy with TRAIL and STI571 in the future.

PMID- 22462556
TI  - Direct observation of a sulfonyl azide excited state and its decay processes by
      ultrafast time-resolved IR spectroscopy.
AB  - The photochemistry of 2-naphthylsulfonyl azide (2-NpSO(2)N(3)) was studied by
      femtosecond time-resolved infrared (TR-IR) spectroscopy and with quantum chemical
      calculations. Photolysis of 2-NpSO(2)N(3) with 330 nm light promotes 2
      NpSO(2)N(3) to its S(1) state. The S(1) excited state has a prominent azide
      vibrational band. This is the first direct observation of the S(1) state of a
      sulfonyl azide, and this vibrational feature allows a mechanistic study of its
      decay processes. The S(1) state decays to produce the singlet nitrene. Evidence
      for the formation of the pseudo-Curtius rearrangement product (2-NpNSO(2)) was
      inconclusive. The singlet sulfonylnitrene (1)(2-NpSO(2)N) is a short-lived
      species (tau ~ 700 +/- 300 ps in CCl(4)) that decays to the lower-energy and
      longer-lived triplet nitrene (3)(2-NpSO(2)N). Internal conversion of the S(1)
      excited state to the ground state S(0) is an efficient deactivation process.
      Intersystem crossing of the S(1) excited state to the azide triplet state
      contributes only modestly to deactivation of the S(1) state of 2-NpSO(2)N(3).

PMID- 22462557
TI  - Improving the management of nitrate pollution in water by the use of isotope
      monitoring: the delta15N, delta18O and delta11B triptych.
AB  - In spite of increasing efforts to reduce nitrogen inputs into ground water from
      intensive agriculture, nitrate (NO(3)) remains one of the major pollutants of
      drinking-water resources worldwide, with NO(3) levels approaching the defined
      limit of 50 mg l(-1) in an increasing number of water bodies. Determining the
      source(s) of contamination in water is an important first step for improving its
      quality by emission control. The Life ISONITRATE project aimed at showing the
      benefit of a multi-isotope approach (delta(15)N and delta(18)O of NO(3), and
      delta(11)B), in addition to conventional hydrogeological analysis, to track the
      origin of NO(3) contamination in water. Based on land use and local knowledge,
      four distinct cases were studied: (1) natural soil NO(3), (2) natural
      denitrification, (3) single source of NO(3) pollution and (4) multiple sources of
      NO(3) pollution. Our results show the added value of combining isotope
      information, compared to knowledge based on local authorities' experience, land
      use and the 'classical' chemical approach, by efficiently identifying the number
      and type of NO(3) source(s) for each watershed studied.

PMID- 22462558
TI  - Comparison of the efficacy and safety of fixed-dose amlodipine/losartan and
      losartan in hypertensive patients inadequately controlled with losartan: a
      randomized, double-blind, multicenter study.
AB  - BACKGROUND: Fixed-dose combination drugs may enhance blood pressure (BP) goal
      attainment through complementary effects and reduced side effects, which leads to
      better compliance. OBJECTIVE: This study aimed to evaluate the efficacy and
      safety profiles of once-daily combination amlodipine/losartan versus losartan.
      METHODS: This was an 8-week, double-blind, multicenter, randomized phase III
      study conducted in outpatient hospital clinics. Korean patients with essential
      hypertension inadequately controlled on losartan 100 mg were administered
      amlodipine/losartan 5 mg/100 mg combination versus losartan 100 mg. The main
      outcome measures were changes in sitting diastolic blood pressure (DBP) and
      sitting systolic blood pressure (SBP) and BP response rate from baseline values,
      which were assessed after 4 and 8 weeks of treatment. Safety and tolerability
      were also assessed. RESULTS: At week 8, both groups achieved significant
      reductions from baseline in DBP (11.7 +/- 7.0 and 3.2 +/- 7.9 mmHg), which was
      significantly greater in the amlodipine/losartan 5 mg/100 mg combination (n = 70)
      group (p < 0.0001). Additionally, the amlodipine/losartan 5 mg/100 mg combination
      group achieved significantly greater reductions in SBP at week 8 and in SBP and
      DBP at week 4 compared with the losartan 100 mg (n = 72) group (all p < 0.0001).
      Response rates were significantly higher in the amlodipine/losartan 5 mg/100 mg
      group versus the losartan 100 mg group (81.4% vs 63.9% at week 4, p < 0.0192;
      90.0% vs 66.7% at week 8, p < 0.001). Both treatments were generally well
      tolerated. CONCLUSION: Switching to a fixed-dose combination therapy of
      amlodipine/losartan 5 mg/100 mg was associated with significantly greater
      reductions in BP and superior achievement of BP goals compared with a maintenance
      dose of losartan 100 mg in Korean patients with essential hypertension
      inadequately controlled on losartan 100 mg. CLINICAL TRIAL REGISTRATION:
      Registered at Clinicaltrials.gov as NCT00940680.

PMID- 22462559
TI  - Chiroptical study of chiral discrimination by amino acid based ionic liquids.
AB  - The chiral discrimination ability of amino acid based chiral ionic liquids is
      studied using chiroptical luminescence techniques. A racemic mixture of
      dissymmetric europium tris(2,6-pyridinedicarboxylate) complexes are dissolved in
      five chiral ionic liquids, including l- and d-alanine methyl ester
      bis(trifluoromethanesulfonimide), l-leucine methyl ester
      bis(trifluoromethanesulfonimide), l-proline methyl ester
      bis(trifluoromethanesulfonimide), and tetrabutylammonium l-alanate. Circularly
      polarized luminescence spectra are measured for the samples over the 283-323 K
      temperature range. Analysis of the spectroscopic results shows that the amino
      acid methyl ester chiral ionic liquids show discrimination with a preference
      (handedness) that corresponds to the stereoisomer (l- vs d-). Most of the chiral
      ionic liquids show enthalpically dominated discrimination, but l-leucine methyl
      ester bis(trifluoromethanesulfonimide) shows entropically dominated chiral
      discrimination. 

PMID- 22462560
TI  - Blunt trauma induced splenic blushes are not created equal.
AB  - BACKGROUND: Currently, evidence of contrast extravasation on computed tomography
      (CT) scan is regarded as an indication for intervention in splenic injuries. In
      our experience, patients transferred from other institutions for
      angioembolization have often resolved the blush upon repeat imaging at our
      hospital. We hypothesized that not all splenic blushes require intervention.
      METHODS: During a 10-year period, we reviewed all patients transferred with blunt
      splenic injuries and contrast extravasation on initial postinjury CT scan.
      RESULTS: During the study period, 241 patients were referred for splenic
      injuries, of whom 16 had a contrast blush on initial CT imaging (88% men, mean
      age 35 +/- 5, mean ISS 26 +/- 3). Eight (50%) patients were managed without
      angioembolization or operation. Comparing patients with and without intervention,
      there was a significant difference in admission heart rate (106 +/- 9 vs 83 +/-
      6) and decline in hematocrit following transfer (5.3 +/- 2.0 vs 1.0 +/- 0.3), but
      not in injury grade (3.9 +/- 0.2 vs 3.5 +/- 0.3), systolic blood pressure (125 +/
      10 vs 115 +/- 6), or age (38.5 +/- 8.2 vs 30.9 +/- 4.7). Of the 8 observed
      patients, 3 underwent repeat imaging immediately upon arrival with resolution of
      the blush. In the intervention group, 4 patients had ongoing extravasation on
      repeat imaging, 2 patients underwent empiric embolization, and 2 patients
      underwent splenectomy for physiologic indications. CONCLUSIONS: For blunt splenic
      trauma, evidence of contrast extravasation on initial CT imaging is not an
      absolute indication for intervention. A period of observation with repeat imaging
      could avoid costly, invasive interventions and their associated sequelae.

PMID- 22462561
TI  - The expressions of CD200 and CD200R molecules on myeloid and lymphoid dendritic
      cells in pre-eclampsia and normal pregnancy.
AB  - PROBLEM: The purpose of our study was to test the hypothesis that the expressions
      of CD200 and CD200R tolerance molecules are increased on peripheral blood
      dendritic cells (DCs) in normal pregnancy and decreased on peripheral blood DCs
      in pre-eclampsia. METHOD OF STUDY: Thirty-three patients with pre-eclampsia, 38
      normal pregnant women, and 10 healthy non-pregnant women were included in the
      study. Dendritic cells were isolated from peripheral blood, stained with
      monoclonal antibodies against blood dendritic cell antigens as well as CD200 and
      CD200R antigens, and estimated using flow cytometry. RESULTS: The expressions of
      CD200 and CD200R molecules on CD1c(+) myeloid and BDCA-2(+) lymphoid DCs in the
      first trimester of normal pregnancy were significantly higher when compared to
      the luteal phase of the ovarian cycle. The expressions of CD200 molecule on
      CD1c(+) myeloid DCs were significantly lower in the third trimester of normal
      pregnancy when compared to the second trimester. The expressions of CD200R
      molecule on CD1c(+) myeloid DCs and BDCA-2(+) lymphoid DCs did not differ in pre
      eclampsia and healthy third trimester pregnant women. However, the expressions of
      CD200 molecule on CD1c(+) myeloid and BDCA-2(+) lymphoid DCs were significantly
      higher in pre-eclampsia when compared to the healthy third trimester pregnant
      women. CONCLUSION: The results suggest increased tolerogenic properties of
      myeloid and lymphoid DCs in normal human pregnancy. Moreover, they suggest a
      decrease in tolerogenic properties of DCs before delivery. It seems possible that
      higher expressions of CD200 molecule on CD1c(+) myeloid and BDCA-2(+) lymphoid
      DCs in pre-eclampsia may constitute the tolerogenic mechanism secondary to the
      pro-inflammatory response that is observed in this syndrome.

PMID- 22462562
TI  - Vitamin D status is associated with bone mineral density and functional exercise
      capacity in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with
      several extrapulmonary effects that contribute to the severity of the disease.
      Vitamin D is suggested to play a role in COPD and its related extrapulmonary
      effects. AIMS: To determine the prevalence of vitamin D deficiency and its
      relation with bone density, muscle strength, and exercise capacity in patients
      with COPD. METHODS: Our cross-sectional study included patients with moderate to
      very severe COPD. We collected data on lung function, body composition, bone
      density, quadriceps muscle strength, 6-minute walking distance, and plasma 25
      hydroxyvitamin D (25(OH)D) concentration. Vitamin D deficiency was defined as
      plasma 25(OH)D concentration below 50 nmol/L. RESULTS: In total, 151 COPD
      patients were included; 87 patients (58%) had vitamin D deficiency. Plasma
      25(OH)D concentration was positively associated with bone density (P = 0.005) and
      6-minute walking distance (P < 0.001) after adjustment for potential confounders.
      Plasma 25(OH)D concentration was not associated with quadriceps muscle strength.
      CONCLUSIONS: The majority of COPD patients had vitamin D deficiency. Plasma
      25(OH)D concentration was positively associated with bone density and exercise
      capacity. Intervention studies are necessary to determine whether vitamin D
      supplementation is of benefit in the prevention or treatment of osteoporosis and
      poor exercise capacity in patients with COPD.

PMID- 22462564
TI  - Mean-shifted surface curvature algorithm for automatic bone shape segmentation in
      orthopedic surgery planning: a sensitivity analysis.
AB  - The results of recent studies concerning statistical bone atlases and automated
      shape analysis are promising with a view to widening the use of surface models in
      orthopedic clinical practice, both in pre-operative planning and in the intra
      operative stages. In this domain, automatic shape analysis is strongly advocated
      because it offers the opportunity to detect morphological and clinical landmarks
      with superior repeatability in comparison to human operators. Surface curvatures
      have been proposed extensively for segmentation and labeling of image and surface
      regions based on their appearance and shape. The surface curvature is an
      invariant that can be exploited for reliable detection of geometric features. In
      this paper, we investigate the potentiality of the algorithm termed mean-shift
      (MS), as applied to a non-linear combination of the minimum and maximum
      curvatures of a surface. We exploited a sensitivity analysis of the algorithm
      parameters across increasing surface resolutions. Results obtained with femur and
      pelvic bone surface data, reconstructed from cadaveric CT scans, demonstrated
      that the information content derived by the MS non-linear curvature overcomes
      both the mean and the Gaussian curvatures and the original non-linear curvature.
      By applying a threshold-based clustering algorithm to the curvature distribution,
      we found that the number of clusters yielded by the MS non-linear curvature is
      significantly lower (by a factor of up to 6) than that obtained by using the
      original non-linear curvature. In conclusion, this study provides valuable
      insights into the use of surface curvature for automatic shape analysis.

PMID- 22462563
TI  - Using sequence data to identify alternative routes and risk of infection: a case
      study of campylobacter in Scotland.
AB  - BACKGROUND: Genetic typing data are a potentially powerful resource for
      determining how infection is acquired. In this paper MLST typing was used to
      distinguish the routes and risks of infection of humans with Campylobacter jejuni
      from poultry and ruminant sources METHODS: C. jejuni samples from animal and
      environmental sources and from reported human cases confirmed between June 2005
      and September 2006 were typed using MLST. The STRUCTURE software was used to
      assign the specific sequence types of the sporadic human cases to a particular
      source. We then used mixed case-case logistic regression analysis to compare the
      risk factors for being infected with C. jejuni from different sources. RESULTS: A
      total of 1,599 (46.3%) cases were assigned to poultry, 1,070 (31.0%) to ruminant
      and 67 (1.9%) to wild bird sources; the remaining 715 (20.7%) did not have a
      source that could be assigned with a probability of greater than 0.95. Compared
      to ruminant sources, cases attributed to poultry sources were typically among
      adults (odds ratio (OR) = 1.497, 95% confidence intervals (CIs) = 1.211, 1.852),
      not among males (OR = 0.834, 95% CIs = 0.712, 0.977), in areas with population
      density of greater than 500 people/km2 (OR = 1.213, 95% CIs = 1.030, 1.431),
      reported in the winter (OR = 1.272, 95% CIs = 1.067, 1.517) and had undertaken
      recent overseas travel (OR = 1.618, 95% CIs = 1.056, 2.481). The poultry assigned
      strains had a similar epidemiology to the unassigned strains, with the exception
      of a significantly higher likelihood of reporting overseas travel in unassigned
      strains. CONCLUSIONS: Rather than estimate relative risks for acquiring
      infection, our analyses show that individuals acquire C. jejuni infection from
      different sources have different associated risk factors. By enhancing our
      ability to identify at-risk groups and the times at which these groups are likely
      to be at risk, this work allows public health messages to be targeted more
      effectively. The rapidly increasing capacity to conduct genetic typing of
      pathogens makes such traced epidemiological analysis more accessible and has the
      potential to substantially enhance epidemiological risk factor studies.

PMID- 22462565
TI  - The "puffed cheek method" to evaluate mucosal thickness: case series.
AB  - OBJECTIVES: Mucosal thickness should be considered in implant treatment planning.
      Needle probing to measure mucosal thickness is invasive and therefore not used in
      routine diagnosis. The "puffed cheek" method is an established technique to
      visualize the vestibule in computed tomography (CT). As CT assesses bone
      availability, a simultaneous mucosal thickness measurement would be useful. The
      aim of this study was to evaluate the reliability of mucosal thickness
      measurement in CT with distended cheeks. MATERIALS AND METHODS: Buccal maxillary
      mucosa thickness was evaluated at four measurement sites in the incisor and molar
      area of 11 patients. Each site was evaluated via CT with cheek distension and
      needle probing. Measurement area was identified with the aid of a thermoplastic
      splint to localize the exact position by a gutta-percha marker point. The
      comparison between the two methods was performed by Bland-Altman diagram.
      RESULTS: The mean clinical thickness was 1.17 mm (+/-0.31) compared to 1.11 mm
      (+/-0.31) in CT evaluation. The mean difference between the two methods was 0.07
      mm (+/-0.40; CI-0.14;0.12, P = 0.88, Krippendorff alpha = 0.38). According to
      Bland-Altman diagram the mucosal thickness may diverge by up to 0.9 mm from the
      radiologic thickness. CONCLUSIONS: The two measurement methods may not be
      interchangeably used. As additional information to three-dimensional bone
      analyses, CT may be performed as a pre-operative soft tissue analysis at most
      implant sites with distended cheeks. Nevertheless, this method yields less valid
      and reliable results than the gold standard.

PMID- 22462566
TI  - Role of transrectal ultrasonography (TRUS) in focal therapy of prostate cancer:
      report from a Consensus Panel.
AB  - What's known on the subject? and What does the study add? Focal therapy
      techniques are emerging in prostate cancer treatment. However, several key
      questions about patient selection, treatment and monitoring still have to be
      addressed. The concept of focal therapy is barely discussed in current urological
      guidelines. In the present manuscript, we report the results of a consensus
      meeting focused on ultrasonography, the most common used urological imaging
      method, in relation to focal therapy of prostate cancer. * To establish a
      consensus on the utility of ultrasonography (US) to select patients for focal
      therapy. Topics were the current status of US to determine focality of prostate
      cancer, to monitor and assess outcome of focal therapy and the diagnostic
      advantages of new US methods. In addition, the biopsy techniques required to
      identify focal lesions were discussed. * Urological surgeons, radiation
      oncologists, radiologists, and basic researchers from Europe and North America
      participated in a consensus meeting on the use of transrectal US (TRUS) in focal
      therapy of prostate cancer. The consensus process was face-to-face and specific
      clinical issues were raised and discussed with agreement sought when possible. *
      TRUS is commonly used and essential for diagnosing men with prostate cancer. It
      is particularly useful for targeting specific anatomical regions or visible
      lesions. However, it has several limitations and there is a need for improvement.
      Newer visualisation techniques, e.g. colour Doppler US, contrast-enhanced US and
      elastography, are being developed but currently there is no US technique that can
      accurately characterise a cancer suitable for focal therapy. Systematic biopsy is
      the only known procedure that allows the identification of prostate cancers
      suitable for focal therapy. Scarce data exist about the role of US for monitoring
      patients during or after ablative therapy. * Consensus was reached on all key
      aspects of the meeting. * US cannot reliably identify focal prostate cancer. New
      US methods show promising results in identifying prostate cancer focality. *
      Currently selecting appropriate candidates for focal therapy should be performed
      using dedicated protocols and biopsy schemes.

PMID- 22462567
TI  - Synthesis, structure, and magnetic properties of a new eight-connected metal
      organic framework (MOF) based on Co4 clusters.
AB  - A hydrothermal reaction of cobalt nitrate, 4,4'-oxybis(benzoic acid) (OBA), 1,2,4
      triazole, and NaOH gave rise to a deep purple colored compound
      [Co(4)(triazolate)(2)(OBA)(3)], I, possessing Co(4) clusters. The Co(4) clusters
      are connected together through the tirazolate moieties forming a two-dimensional
      layer that closely resembles the TiS(2) layer. The layers are pillared by the OBA
      units forming the three-dimensional structure. To the best of our knowledge, this
      is the first observation of a pillared TiS(2) layer in a metal-organic framework
      compound. Magnetic studies in the temperature range 1.8-300 K indicate strong
      antiferromagetic interactions for Co(4) clusters. The structure as well as the
      magnetic behavior of the present compound has been compared with the previously
      reported related compound [Co(2)(MU(3)-OH)(MU(2)-H(2)O)(pyrazine)(OBA)(OBAH)]
      prepared using pyrazine as the linker between the Co(4) clusters.

PMID- 22462568
TI  - Phytochrome A increases tolerance to high evaporative demand.
AB  - Stresses resulting from high transpiration demand induce adjustments in plants
      that lead to reductions of water loss. These adjustments, including changes in
      water absorption, transport and/or loss by transpiration, are crucial to normal
      plant development. Tomato wild type (WT) and phytochrome A (phyA)-mutant plants,
      fri1-1, were exposed to conditions of either low or high transpiration demand and
      several morphological and physiological changes were measured during stress
      conditions. Mutant plants rapidly wilted compared to WT plants after exposure to
      high evaporative demand. Root size and hydraulic conductivity did not show
      significant differences between genotypes, suggesting that water absorption and
      transport through this organ could not explain the observed phenotype. Moreover,
      stomatal density was similar between genotypes, whereas transpiration and
      stomatal conductance were both lower in mutant than in WT plants. This was
      accompanied by a lower stem-specific hydraulic conductivity in mutant plants,
      which was associated to lower xylem vessel number and transversal area in fri1-1
      plants, producing a reduction in water supply to the leaves, which rapidly wilted
      under high evaporative demand. PhyA signaling might facilitate the adjustment to
      environments differing widely in water evaporative demand in part through the
      modulation of xylem dimensions.

PMID- 22462569
TI  - Movement of abdominal structures on magnetic resonance imaging during positioning
      changes related to lateral lumbar spine surgery: a morphometric study: Clinical
      article.
AB  - OBJECT: The minimally invasive lateral interbody fusion of the lumbar spine
      through a retroperitoneal transpsoas approach has become increasingly used.
      Although preoperative imaging is performed supine, the procedure is performed
      with the patient in the lateral decubitus position. The authors measured the
      changes in location of the psoas muscle, aorta, inferior vena cava (IVC), iliac
      vessels, and kidneys with regard to the fixed lumbar spine when moving from a
      supine to a lateral decubitus position. METHODS: Unenhanced lumbar MRI scans were
      performed using a 3T magnet in 10 skeletally mature volunteers in the supine,
      left lateral decubitus (LLD), and right lateral decubitus (RLD) positions.
      Positional changes in the aorta, IVC, iliac vessels, and kidneys were then
      analyzed at all lumbar levels when moving from supine to RLD and supine to LLD.
      Values are presented as group means. RESULTS: When the position was changed from
      supine to RLD, both the aorta and the IVC moved up to 6 mm to the right, with
      increased movement caudally at L3-4. The aorta was displaced 2 mm anteriorly at
      L1-2, and the IVC moved 3 mm anteriorly at L1-2 and L2-3 and 1 mm posteriorly at
      L3-4. The left kidney moved 22 mm anteriorly and 15 mm caudally, while the right
      kidney moved 9 mm rostrally. When the position was changed from supine to LLD,
      the aorta moved 1.5 mm to the left at all levels, with very minimal
      anterior/posterior displacement. The IVC moved up to 10 mm to the left and 12 mm
      anteriorly, with increased movement rostrally at L1-2. The left kidney moved 3 mm
      anteriorly and 1 mm rostrally, while the right kidney moved 20 mm anteriorly and
      5 mm caudally. The bifurcation of the aorta was an average of 18 mm above the L4
      5 disc space, while the convergence of the iliac veins to form the IVC was at the
      level of the disc space. The iliopsoas did not move in any quantifiable direction
      when the position was changed from supine to lateral; its shape, however, may
      change to become more flat or rounded. When the position was changed from supine
      to RLD, the right iliac vein moved posteriorly an average of 1.5 mm behind the
      anterior vertebral body (VB) line (a horizontal line drawn on an axial image at
      the anterior VB), while the other vessels stayed predominantly anterior to the
      disc space. When the position was changed from supine to LLD, the right iliac
      vein moved to a position 1.4 mm anterior to the anterior VB line. There was
      negligible movement of the other vessels in this position. CONCLUSIONS: The
      authors showed that the aorta, IVC, and kidneys moved a significant distance away
      from the surgical corridor with changes in position. At the L4-5 level, a left
      sided approach may be riskier because the right common iliac vein trends
      posteriorly and into the surgical corridor, whereas in a right-sided approach it
      trends anteriorly.

PMID- 22462570
TI  - The effects of carpentry on heterotopic ossification and mobility in cervical
      arthroplasty: determination by computed tomography with a minimum 2-year follow
      up: Clinical article.
AB  - OBJECT: Heterotopic ossification (HO) after cervical arthroplasty can limit the
      mobility of an artificial disc. In this study the authors used CT scanning to
      assess the formation of HO with the goal of investigating the correlation between
      the carpentry of arthroplasty, formation of HO, mobility, and clinical outcomes.
      METHODS: A retrospective review of medical records, radiological studies, and
      clinical evaluations was conducted for consecutive patients who underwent 1- or 2
      level cervical arthroplasty with the Bryan disc. The patients underwent follow-up
      for more than 24 months. The formation of HO was assessed using CT scanning as
      the final determination. The perfectness of carpentry for each arthroplasty level
      was scrutinized using criteria composed of 2 parameters (postoperative shell
      kyphosis and inadequate endplate coverage). Levels were divided into the optimal
      carpentry group and the suboptimal carpentry group. Radiographic and clinical
      outcomes, including the visual analog scale and neck disability index, were
      compared between the groups. RESULTS: A total of 107 levels of Bryan discs were
      placed in 75 patients (mean age 46.71 +/- 9.94 years) and were analyzed. There
      was a male predominance of 68.0% (51 men), and the mean follow-up duration was
      38.56 +/- 9.66 months. Heterotopic ossification was identified in 60 levels
      (56.1%) by CT scanning. Most cases of HO were low grade and did not correlate
      with the limitation in the segmental motion of the arthroplasty device. There
      were no significant differences in terms of age, sex, and number of arthroplasty
      levels between the optimal and the suboptimal carpentry groups. However, the
      suboptimal carpentry group had significantly more high-grade HO (>= Grade 2) than
      the optimal carpentry group (13 levels [12.1%] vs 7 levels [6.5%], p = 0.027).
      There were also more immobile (range of motion < 3 degrees ) artificial discs in
      the suboptimal carpentry group than the optimal carpentry group (11 levels
      [10.3%] vs 4 levels [3.7%], p = 0.010). The clinical outcomes (neck and arm
      visual analog scale scores and Neck Disability Index) in both groups were
      similarly good. CONCLUSIONS: Shell kyphosis and inadequate endplate coverage have
      adverse effects on the formation of HO and segmental mobility after cervical
      arthroplasty with the Bryan artificial disc. Appropriate carpentry is the more
      important factor in determining the maintenance of segmental motion. Although the
      midterm clinical outcome remained similarly good regardless of HO, the carpentry
      of cervical arthroplasty should not be overlooked. Further studies are needed to
      clarify the etiology of HO.

PMID- 22462571
TI  - Sagittal realignment failures following pedicle subtraction osteotomy surgery:
      are we doing enough?: Clinical article.
AB  - OBJECT: Pedicle subtraction osteotomy (PSO) is a surgical procedure that is
      frequently performed on patients with sagittal spinopelvic malalignment. Although
      it allows for substantial spinopelvic realignment, suboptimal realignment
      outcomes have been reported in up to 33% of patients. The authors' objective in
      the present study was to identify differences in radiographic profiles and
      surgical procedures between patients achieving successful versus failed
      spinopelvic realignment following PSO. METHODS: This study is a multicenter
      retrospective consecutive PSO case series. The authors evaluated 99 cases
      involving patients who underwent PSO for sagittal spinopelvic malalignment.
      Because precise cutoffs of acceptable residual postoperative sagittal vertical
      axis (SVA) values have not been well defined, comparisons were focused between
      patient groups with a postoperative SVA that could be clearly considered either a
      success or a failure. Only cases in which the patients had a postoperative SVA of
      less than 50 mm (successful PSO realignment) or more than 100 mm (failed PSO
      realignment) were included in the analysis. Radiographic measures and PSO
      parameters were compared between successful and failed PSO realignments. RESULTS:
      Seventy-nine patients met the inclusion criteria. Successful realignment was
      achieved in 61 patients (77%), while realignment failed in 18 (23%). Patients
      with failed realignment had larger preoperative SVA (mean 217.9 vs 106.7 mm, p <
      0.01), larger pelvic tilt (mean 36.9 degrees  vs 30.7 degrees , p < 0.01), larger
      pelvic incidence (mean 64.2 degrees  vs 53.7 degrees , p < 0.01), and greater
      lumbar lordosis-pelvic incidence mismatch (-47.1 degrees  vs -30.9 degrees , p <
      0.01) compared with those in whom realignment was successful. Failed and
      successful realignments were similar regarding the vertebral level of the PSO,
      the median size of wedge resection 22.0 degrees  (interquartile range 16.5
      degrees -28.5 degrees ), and the numerical changes in pre- and postoperative
      spinopelvic parameters (p > 0.05). CONCLUSIONS: Patients with failed PSO
      realignments had significantly larger preoperative spinopelvic deformity than
      patients in whom realignment was successful. Despite their apparent need for
      greater correction, the patients in the failed realignment group only received
      the same amount of correction as those in the successfully realigned patients. A
      single-level standard PSO may not achieve optimal outcome in patients with high
      preoperative spinopelvic sagittal malalignment. Patients with large spinopelvic
      deformities should receive larger osteotomies or additional corrective procedures
      beyond PSOs to avoid undercorrection.

PMID- 22462572
TI  - Galvanically replaced hollow Au-Ag nanospheres: study of their surface plasmon
      resonance.
AB  - We synthesized hollow Au-Ag nanospheres (NSs) by employing a galvanic replacement
      reaction between HAuCl4 and Ag NSs. Uniform Ag NSs with controllable sizes were
      synthesized as sacrificial templates by a seed-mediated strategy. The atomic
      ratio of Au to Ag in Au-Ag NSs was tunable by controlling the reagent
      concentration. UV-vis extinction spectra acquired from well-dispersed colloidal
      NS solutions were used to investigate the optical properties of the solutions. In
      addition to a common dipole mode exhibited on most transition metal
      nanoparticles, we observed a quadrupole plasmon resonance mode when the diameters
      of the Ag and Au-Ag NSs were larger than 100 nm. The quadrupole and dipole peaks
      both shifted to longer wavelengths with increased Au content in Au-Ag NSs. The
      experimental observation of optical properties of hollow Au-Ag NSs was compared
      with the theoretical simulation using DDA calculation, showing a good agreement. 

PMID- 22462573
TI  - Treatment of refractory tonic status epilepticus with intravenous lacosamide.

PMID- 22462574
TI  - Causal or casual association between lamotrigine and sudden unexpected death in
      females with epilepsy?

PMID- 22462575
TI  - Thyroid hormones may contribute to vascular risk factors and atherosclerosis.

PMID- 22462576
TI  - Substitution of California Verbal Learning Test, second edition for Verbal Paired
      Associates on the Wechsler Memory Scale, fourth edition.
AB  - Two common measures used to evaluate verbal learning and memory are the Verbal
      Paired Associates (VPA) subtest from the Wechsler Memory Scales (WMS) and the
      second edition of the California Verbal Learning Test (CVLT-II). For the fourth
      edition of the WMS, scores from the CVLT-II can be substituted for VPA; the
      present study sought to examine the validity of the substitution. For each
      substitution, paired-samples t tests were conducted between original VPA scaled
      scores and scaled scores obtained from the CVLT-II substitution to evaluate
      comparability. Similar comparisons were made at the index score level. At the
      index score level, substitution resulted in significantly lower scores for the
      AMI (p = .03; r = .13) but not for the IMI (p = .29) or DMI (p = .09). For the
      subtest scores, substituted scaled scores for VPA were not significantly
      different from original scores for the immediate recall condition (p = .20) but
      were significantly lower at delayed recall (p = .01). These findings offer
      partial support for the substitution. For both the immediate and delayed
      conditions, the substitution produced generally lower subtest scores compared to
      original VPA subtest scores.

PMID- 22462577
TI  - PLS-optimal: a stepwise D-optimal design based on latent variables.
AB  - Several applications, such as risk assessment within REACH or drug discovery,
      require reliable methods for the design of experiments and efficient testing
      strategies. Keeping the number of experiments as low as possible is important
      from both a financial and an ethical point of view, as exhaustive testing of
      compounds requires significant financial resources and animal lives. With a large
      initial set of compounds, experimental design techniques can be used to select a
      representative subset for testing. Once measured, these compounds can be used to
      develop quantitative structure-activity relationship models to predict properties
      of the remaining compounds. This reduces the required resources and time. D
      Optimal design is frequently used to select an optimal set of compounds by
      analyzing data variance. We developed a new sequential approach to apply a D
      Optimal design to latent variables derived from a partial least squares (PLS)
      model instead of principal components. The stepwise procedure selects a new set
      of molecules to be measured after each previous measurement cycle. We show that
      application of the D-Optimal selection generates models with a significantly
      improved performance on four different data sets with end points relevant for
      REACH. Compared to those derived from principal components, PLS models derived
      from the selection on latent variables had a lower root-mean-square error and a
      higher Q2 and R2. This improvement is statistically significant, especially for
      the small number of compounds selected.

PMID- 22462578
TI  - Binding of the IclR-type regulator HutR in the histidine utilization (hut) gene
      cluster of the human pathogen Corynebacterium resistens DSM 45100.
AB  - The genome of the human pathogen Corynebacterium resistens DSM 45100 is equipped
      with a histidine utilization (hut) gene cluster encoding a four-step pathway for
      the catabolism of l-histidine and a transcriptional regulator of the IclR
      superfamily, now named HutR. The utilization of l-histidine might be relevant for
      the growth of C. resistens in its natural habitat, probably the histidine-rich
      inguinal and perineal areas of the human body. The ability of C. resistens to
      utilize l-histidine as a sole source of nitrogen was demonstrated by growth
      assays in synthetic minimal media. Reverse transcriptase PCRs revealed enhanced
      transcript levels of the hut genes in C. resistens cells grown in the presence of
      l-histidine. Promoter-probe assays showed that the hut genes are organized in
      three transcription units: hutHUI, hutR, and hutG. The respective transcriptional
      start sites were mapped by 5' RACE-PCR to detected putative promoter regions. DNA
      band shift assays with purified HutR protein identified the 14-bp DNA sequence
      TCTGwwATwCCAGA located upstream of the mapped promoters. This DNA motif includes
      a 4-bp terminal palindrome, which turned out to be essential for HutR binding in
      vitro. These data add a new physiological function to the large IclR family of
      transcriptional regulators.

PMID- 22462579
TI  - Does insulin resistance co-exist with glucocorticoid resistance in the metabolic
      syndrome? Studies comparing skin sensitivity to glucocorticoids in individuals
      with and without acanthosis nigricans.
AB  - BACKGROUND: The metabolic syndrome is associated with increased risk for both
      diabetes and coronary artery disease, which insulin resistance alone does not
      satisfactorily explain. We propose an additional and complementary underlying
      mechanism of glucocorticoid resistance. RESULTS: Using acanthosis nigricans (AN)
      and skin vasoconstrictor (SVC) response to topically applied beclomethasone
      dipropionate as markers of insulin and glucocorticoid resistance, respectively,
      we compared anthropometric, biochemical, pro-inflammatory markers and the SVC
      response in subjects with AN in two studies: STUDY 1 was used to compare subjects
      with AN (Grade 4, n = 32), with those without AN (n = 68) while STUDY 2 compared
      these responses among a cross-section of diabetic patients (n = 109) with varying
      grades of AN (grade 0, n = 30; grade 1, n = 24; grade 2, n = 18; grade 3, n = 25;
      grade 4, n = 12). FINDINGS: In both studies there was an inverse relationship
      between AN Grade 4 and the SVC response, (P < 0.001). In STUDY 1, AN Grade 4 was
      associated with age, waist circumference, BMI, fasting blood glucose, plasma
      lipids and hs-CRP (P < 0.05). SVC was an independent predictor of CRP and those
      with combined AN and a negative SVC response, CRP levels were highest. In Study 2
      when the SVC response in subjects with type 2 diabetes mellitus with varying
      degrees of AN was studied, it showed that for any degree of AN, the SVC response
      is more likely to be negative and was independent of gender and ethnicity.
      CONCLUSION: An absent SVC response represents a new biomarker for the metabolic
      syndrome and the exaggerated inflammatory response, which characterizes the
      metabolic syndrome, may be an outcome of deficient glucocorticoid action in
      vascular tissue.

PMID- 22462580
TI  - Mycobacteria and the intraphagosomal environment: take it with a pinch of
      salt(s)!
AB  - Ancient protozoan phagocytes and modern professional phagocytes of metazoans,
      such as macrophages, employ evolutionarily conserved mechanisms to kill microbes.
      These mechanisms rely on microbial ingestion, followed by maturation of the
      phagocytic vacuole, or so-called phagosome. Phagosome maturation includes a
      series of fusion and fission events with the host cell endosomes and lysosomes,
      leading to a rapid increase of the degradative properties of the vacuole and to
      the destruction of the ingested microbe within a very hostile intracellular
      compartment, the phagolysosome. Historically, the mechanisms and weapons used by
      phagocytes to kill microbes have been separated into different classes.
      Phagosomal acidification, together with the production of reactive oxygen and
      nitrogen species, the selective manipulation of various ions in the phagosomal
      lumen, and finally the engagement of a battery of acidic hydrolases, are well
      recognized players in this process. However, it is relatively recently that
      interconnections among these mechanisms have become apparent. In this review, we
      will focus on some emerging concepts about these interconnected aspects of the
      warfare at the host-pathogen interface, using mostly Mycobacterium tuberculosis
      as an example of intracellular pathogen. In particular, recent discoveries on the
      role of phagosomal ions and other chemicals in the control of pathogens, as well
      as mechanisms evolved by intracellular pathogens to circumvent or even exploit
      the weapons of the host cell will be discussed.

PMID- 22462582
TI  - Recent advances in manganese oxide nanocrystals: fabrication, characterization,
      and microstructure.

PMID- 22462581
TI  - Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting
      breast cancer metastasis.
AB  - BACKGROUND: Previous studies suggest that oxidative stress plays an important
      role in the development of breast cancer. There is a significant inverse
      relationship between HDL and the risk and mortality of breast cancer. However, it
      is well known that under conditions of oxidative stress, such as breast cancer,
      HDL can be oxidatively modifiedand these modifications may have an effect on the
      functions of HDL. The purpose of this study is to determine the different effects
      of normal and oxidized (caused by hypochlorite-induced oxidative stress) HDL on
      breast cancer cell metastasis. METHODS: Human breast cancer cell lines were
      treated with normal and hypochlorite-oxidized HDL, and then cell metastasis
      potency in vivo and the abilities of migration, invasion, adhesion to HUVEC and
      ECM in vitro were examined. Integrin expression and PKC activity were evaluated,
      and PKC inhibitor and PKC siRNA was applied. RESULTS: We found hypochlorite
      oxidized HDL dramatically promotes breast cancer cell pulmonary metastasis
      (133.4% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 164.3%
      increase at P < 0.01 for MCF7 by tail vein injection) and hepatic metastasis
      (420% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 1840%
      fold increase at P < 0.001 for MCF7 by tail vein injection) in nude mice, and
      stimulates higher cell invasion (85.1% increase at P < 0.00 l for MDA-MB-231;
      88.8% increase at P < 0.00 l for MCF7;), TC-HUVEC adhesion (43.4% increase at P <
      0.00 l for MDA-MB-231; 35.2% increase at P < 0.00 l for MCF7), and TC-ECM
      attachment (41.0% increase at P < 0.00 l for MDA-MB-231; 26.7% increase at P <
      0.05 for MCF7) in vitro compared with normal HDL. The data also shows that the
      PKC pathway is involved in the abnormal actions of hypochlorite-oxidized HDL.
      CONCLUSIONS: Our study demonstrated that HDL under hypochlorite-induced oxidative
      stress stimulates breast cancer cell migration, invasion, adhesion to HUVEC and
      ECM, thereby promoting metastasis of breast cancer. These results suggest that
      HDL-based treatments should be considered for treatment of breast cancer
      patients.

PMID- 22462583
TI  - Sexual medicine, sexual abuse, and the law.

PMID- 22462585
TI  - Conversion of low-flow to high-flow priapism: a case report and review (CME).
AB  - Priapism is defined as an erection lasting greater than 4 hours. It is grouped
      into three subtypes: ischemic (low flow), nonischemic (high flow), and stuttering
      priapism. We present an interesting case and review of the conversion from a low
      flow to a high-flow priapism. This conversion has rarely been reported. It has
      resulted from treatment of low-flow priapism with minimally invasive procedures
      including injection therapy as well as more invasive distal and proximal shunt
      procedures. Penile Doppler ultrasound and angiogram are particularly important to
      the clinician in the diagnosis and treatment of this rare entity.

PMID- 22462587
TI  - Female orgasm(s): one, two, several.
AB  - INTRODUCTION: There is general agreement that it is possible to have an orgasm
      thru the direct simulation of the external clitoris. In contrast, the possibility
      of achieving climax during penetration has been controversial. METHODS: Six
      scientists with different experimental evidence debate the existence of the
      vaginally activated orgasm (VAO). MAIN OUTCOME MEASURE: To give reader of The
      Journal of Sexual Medicine sufficient data to form her/his own opinion on an
      important topic of female sexuality. RESULTS: Expert #1, the Controversy's
      section Editor, together with Expert #2, reviewed data from the literature
      demonstrating the anatomical possibility for the VAO. Expert #3 presents
      validating women's reports of pleasurable sexual responses and adaptive
      significance of the VAO. Echographic dynamic evidence induced Expert # 4 to
      describe one single orgasm, obtained from stimulation of either the external or
      internal clitoris, during penetration. Expert #5 reviewed his elegant experiments
      showing the uniquely different sensory responses to clitoral, vaginal, and
      cervical stimulation. Finally, the last Expert presented findings on the
      psychological scenario behind VAO. CONCLUSION: The assumption that women may
      experience only the clitoral, external orgasm is not based on the best available
      scientific evidence.

PMID- 22462589
TI  - Something is wrong with my penis shape!

PMID- 22462590
TI  - Clinical audit of health promotion of vitamin D in one general practice.
AB  - BACKGROUND: The clinical audit of vitamin D health promotion in one Australian
      general practice was undertaken by measuring health service use and serum 25
      hydroxyvitamin D levels in 995 patients aged 45 to 49 years. FINDINGS: Over 3
      years, 486 (51%) patients had a Medicare funded Health Assessment. More women
      (54%) were assessed than men (46%) p = 0.010. Mean 25-OHD was higher for men
      (70.0 nmol/l) than women (60.3 nmol/l) p < 0.001. More patients had their weight
      measured (50%) than 25-OHD tested (28%).Among 266 patients who had a 25-OHD test,
      68 (26%) had normal levels 80+ nmol/l, 109 (41%) were borderline 51-79 nmol/l,
      and 89 (33%) were low < 51 nmol/l. Mean 25-OHD was higher in summer (73.7 nmol/l)
      than winter (54.7 nmol/l) p < 0.001. Sending uninvited written information about
      25-OHD had no effect on patients' subsequent attendance. CONCLUSIONS: Health
      promotion information about vitamin D was provided to 50% of a targeted group of
      patients over a one-year period. Provision of this information had no effect on
      the uptake rates of an invitation to attend for a general health assessment.

PMID- 22462591
TI  - Three-dimensional atlas of iron, copper, and zinc in the mouse cerebrum and
      brainstem.
AB  - Atlases depicting molecular and functional features of the brain are becoming an
      integral part of modern neuroscience. In this study we used laser ablation
      inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantitatively measure
      iron (Fe), copper (Cu), and zinc (Zn) levels in a serially sectioned C57BL/6
      mouse brain (cerebrum and brainstem). Forty-six sections were analyzed in a
      single experiment of approximately 158 h in duration. We constructed a 46-plate
      reference atlas by aligning quantified images of metal distribution with
      corresponding coronal sections from the Allen Mouse Brain Reference Atlas. The 46
      plates were also used to construct three-dimensional models of Fe, Cu, and Zn
      distribution. This atlas represents the first reconstruction of quantitative
      trace metal distribution through the brain by LA-ICPMS and will facilitate the
      study of trace metals in the brain and help to elucidate their role in
      neurobiology.

PMID- 22462592
TI  - In memorium: earl muetterties.

PMID- 22462593
TI  - Low-voltage bendable pentacene thin-film transistor with stainless steel
      substrate and polystyrene-coated hafnium silicate dielectric.
AB  - The hafnium silicate and aluminum oxide high-k dielectrics were deposited on
      stainless steel substrate using atomic layer deposition process and
      octadecyltrichlorosilane (OTS) and polystyrene (PS) were treated improve
      crystallinity of pentacene grown on them. Besides, the effects of the pentacene
      deposition condition on the morphologies, crystallinities and electrical
      properties of pentacene were characterized. Therefore, the surface treatment
      condition on dielectric and pentacene deposition conditions were optimized. The
      pentacene grown on polystyrene coated high-k dielectric at low deposition rate
      and temperature (0.2-0.3 A/s and R.T.) showed the largest grain size (0.8-1.0
      MUm) and highest crystallinity among pentacenes deposited various deposition
      conditions, and the pentacene TFT with polystyrene coated high-k dielectric
      showed excellent device-performance. To decrease threshold voltage of pentacene
      TFT, the polystyrene-thickness on high-k dielectric was controlled using
      different concentration of polystyrene solution. As the polystyrene-thickness on
      hafnium silicate decreases, the dielectric constant of polystyrene/hafnium
      silicate increases, while the crystallinity of pentacene grown on
      polystyrene/hafnium silicate did not change. Using low-thickness polystyrene
      coated hafnium silicate dielectric, the high-performance and low voltage
      operating (<5 V) pentacene thin film transistor (MU: ~2 cm(2)/(V s), on/off
      ratio, >1 * 10(4)) and complementary inverter (DC gains, ~20) could be
      fabricated.

PMID- 22462594
TI  - Impact of revisions to the F-Tag 309 surveyors' interpretive guidelines on pain
      management among nursing home residents.
AB  - BACKGROUND: On 31 March 2009, the US Centers for Medicare & Medicaid Services
      (CMS) provided revised guidance for meeting compliance in the evaluation and
      management of pain in nursing home residents, known as F-Tag 309. OBJECTIVE: The
      aim of the study was to estimate the extent to which implementation of revisions
      to the surveyors' interpretive guidelines for F-Tag 309 improved recognition and
      management of pain among nursing home residents. METHODS: The impact of the
      revisions to guidance on F-Tag 309 on pain in nursing home residents was
      investigated. The study was quasi-experimental in design and included 174 for
      profit nursing homes in 19 US states. Nursing home residents with >=2 Minimum
      Data Set (MDS) assessments between 1 January 2007 and 30 March 2009 (before the
      revisions to the guidelines; n = 8449) and between 31 March 2009 and 31 December
      2009 (after the revisions; n = 1400) were included. The MDS assessments provided
      information on pain, analgesic use and cognitive, functional and emotional
      status. Separate logistic regression models that adjusted for clustering effects
      of residents residing in nursing homes provided estimates of the relationship
      between the implementation of the revisions to F-Tag 309 and the prevalence of
      pain and its management. RESULTS: Pain was more likely to be documented in the
      period after the revisions were implemented. The odds of pain being documented on
      at least one of two consecutive MDS assessments increased after the revisions to
      the guidelines were implemented (adjusted odds ratio [OR] 1.15; 95% confidence
      interval [CI] 1.01, 1.31). Increases in scheduled analgesic prescription were
      observed in the post-revision era (adjusted OR 1.38; 95% CI 1.21,1.57).
      CONCLUSION: The implementation of revisions to the surveyors' interpretive
      guidelines for F-Tag 309 improved recognition and management of pain as well as
      analgesic use in nursing home residents with documented non-cancer pain. Use of
      directed language as part of the surveyors' interpretive guidelines may be a
      viable approach to stimulating improvements in pain documentation and management.

PMID- 22462595
TI  - Primary electron donor(s) in isolated reaction center of photosystem II from
      Chlamydomonas reinhardtii.
AB  - Isolated reaction centers (RCs) from wild-type Chlamydomonas (C.) reinhardtii of
      Photosystem II (PSII), at different levels of intactness, were studied to provide
      more insight into the nature of the charge-separation (CS) pathway(s). We argue
      that previously studied D1/D2/Cytb559 complexes (referred to as RC680), with
      ChlD1 serving as the primary electron donor, contain destabilized D1 and D2
      polypeptides and, as a result, do not provide a representative model system for
      the intact RC within the PSII core. The shapes of nonresonant transient hole
      burned (HB) spectra obtained for more intact RCs (referred to as RC684) are very
      similar to P(+)QA(-) - PQA absorbance difference and triplet minus singlet
      spectra measured in PSII core complexes from Synechocystis PCC 6803 [Schlodder et
      al. Philos. Trans. R. Soc. London, Ser. B2008, 363, 1197]. We show that in the
      RC684 complexes, both PD1 and ChlD1 may serve as primary electron donors, leading
      to two different charge separation pathways. Resonant HB spectra cannot
      distinguish the CS times corresponding to different paths, but it is likely that
      the zero-phonon holes (ZPHs) observed in the 680-685 nm region (corresponding to
      CS times of ~1.4-4.4 ps) reveal the ChlD1 pathway; conversely, the observation of
      charge-transfer (CT) state(s) in RC684 (in the 686-695 nm range) and the absence
      of ZPHs at lambdaB > 685 nm likely stem from the PD1 pathway, for which CS could
      be faster than 1 ps. This is consistent with the finding of Krausz et al.
      [Photochem. Photobiol. Sci.2005, 4, 744] that CS in intact PSII core complexes
      can be initiated at low temperatures with fairly long-wavelength excitation. The
      lack of a clear shift of HB spectra as a function of excitation wavelength within
      the red-tail of the absorption (i.e., 686-695 nm) and the absence of ZPHs suggest
      that the lowest-energy CT state is largely homogeneously broadened. On the other
      hand, in usually studied destabilized RCs, that is, RC680, for which CT states
      have never been experimentally observed, ChlD1 is the most likely electron donor.

PMID- 22462596
TI  - Chronic amitriptyline overdose in a child.
AB  - Amitriptyline, a tricyclic antidepressant, has a well-described toxicity profile,
      and acute ingestions are common in the pediatric toxicology world. However,
      little can be found in the literature regarding chronic overdose. We describe a
      case of a 6-year-old girl who was prescribed amitriptyline 30 mg nightly for
      sleep problems, but was mistakenly given 300 mg (15 mg/kg) nightly for over a
      month. She was noted to have mental status changes and difficulty reading several
      days after starting the medication. She presented to the local children's
      hospital in status epilepticus with significant cardiac conduction abnormalities
      on ECG. Her total amitriptyline/nortriptyline level was found to be 1676 ng/mL
      (normal therapeutic level 50-300 ng/mL). She was treated for several days with
      sodium bicarbonate. Within 24 h, her neurologic status improved and had returned
      to baseline within several days. Her ECG normalized, and she was discharged home,
      without apparent sequelae. A brief discussion of possible protective mechanisms
      (including pharmacogenomic) is presented.

PMID- 22462597
TI  - Dropping acid at school: hydrochloric acid exposures in chemistry class.

PMID- 22462598
TI  - Intentional ingestion of cyanoacrylate.

PMID- 22462599
TI  - Bortezomib-associated fatal liver failure in a haemodialysis patient with
      multiple myeloma.
AB  - CONTEXT: Bortezomib is a proteasome inhibitor with excellent antimyeloma
      activity. The most frequent toxic side effects are gastrointestinal, neuropathy
      and thrombocytopenia. The liver was not considered an important target organ for
      toxicity until one case of bortezomib-induced severe hepatitis was reported in a
      patient with multiple myeloma. CASE REPORT: We describe a patient developing
      acute cholestatic and parenchymal hepatitis complicated by fatal liver failure
      after bortezomib therapy for multiple myeloma. DISCUSSION: The importance of
      being aware of this potential fatal complication is emphasized considering that
      this drug is increasingly prescribed and in order to discontinue this drug if
      liver adverse reaction is suspected.

PMID- 22462600
TI  - Time variations of 222Rn concentration and air exchange rates in a Hungarian
      cave.
AB  - A long-term radon concentration monitoring was carried out in the Pal-volgy cave,
      Budapest, Hungary, for 1.5 years. Our major goal was to determine the time
      dependence of the radon concentration in the cave to characterise the air
      exchange and define the most important environmental parameters that influence
      the radon concentration inside the cave. The radon concentration in the cave air
      was measured continuously by an AlphaGuard radon monitor, and meteorological
      parameters outside the cave were collected simultaneously. The air's radon
      concentration in the cave varied between 104 and 7776 Bq m(-3), the annual
      average value was 1884+/-85 Bq m(-3). The summer to winter radon concentration
      ratio was as high as 21.8. The outside air temperature showed the strongest
      correlation with the radon concentration in the cave, the correlation coefficient
      (R) was 0.76.

PMID- 22462602
TI  - Human papillomavirus (HPV) vaccine policy and evidence-based medicine: are they
      at odds?

PMID- 22462601
TI  - The benefits and barriers to physical activity and lifestyle interventions for
      osteoarthritis affecting the adult knee.
AB  - Osteoarthritis prevalence is increasing, placing greater demands on healthcare
      and future socioeconomic costing models. Exercise and non-pharmacological methods
      should be employed to manage this common and disabling disease. Expectations at
      all stages of disease are increasing with a desire to remain active and
      independent. Three key areas have been reviewed; the evidence for physical
      activity, lifestyle changes and motivational techniques concerning knee
      osteoarthritis and the barriers to instituting such changes. Promotion of
      activity in primary care is discussed and evidence for compliance has been
      reviewed. This article reviews a subject that is integral to all professionals
      involved with osteoarthritis care.

PMID- 22462603
TI  - Fruit-specific overexpression of wound-induced tap1 under E8 promoter in tomato
      confers resistance to fungal pathogens at ripening stage.
AB  - Based on high economic importance and nutritious value of tomato fruits and as
      previous studies employed E8 promoter in fruit ripening-specific gene expression,
      we have developed transgenic tomato plants overexpressing tomato anionic
      peroxidase cDNA (tap1) under E8 promoter. Stable transgene integration was
      confirmed by polymerase chain reaction (PCR) and Southern analysis for nptII.
      Northern blotting confirmed elevated tap1 levels in the breaker- and red-ripe
      stages of T(1)  transgenic fruits, whereas wild-type (WT) plants did not show
      tap1 expression in these developmental stages. Further, tap1 expression levels
      were significantly enhanced in response to wounding in breaker- and red-ripe
      stages of transgenic fruits, whereas wound-induced expression of tap1 was not
      detected in WT fruits. Confocal microscopy revealed high accumulation of phenolic
      compounds at the wound site in transgenic fruits suggesting a role of tap1 in
      wound-induced phenolic polymerization. Total peroxidase activity has increased
      remarkably in transgenic pericarp tissues in response to wounding, while very
      less or minimal levels were recorded in WT pericarp tissues. Transgenic fruits
      also displayed reduced post-harvest decay and increased resistance toward
      Alternaria alternata and Fusarium solani infection with noticeable inhibition in
      lesion formation. Conidiospore germination and mycelial growth of F. solani were
      severely inhibited when treated with E8-tap1 fruit extracts compared to WT
      fruits. 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay
      showed reduced spore viability when incubated in E8-tap1 fruit extracts. Thus,
      fruit-specific expression of tap1 using E8 promoter is associated with enhanced
      total peroxidase activity and high phenolic accumulation in fruits with minimized
      post-harvest deterioration caused by wounding and fungal attack in tomato fruits.

PMID- 22462604
TI  - Genetic variations in APPL2 are associated with overweight and obesity in a
      Chinese population with normal glucose tolerance.
AB  - BACKGROUND: APPL1 and APPL2 are two adaptor proteins, which can mediate
      adiponectin signaling via binding to N terminus of adiponectin receptors in
      muscle cells. Genes encoding adiponectin and adiponectin receptors contribute to
      insulin resistance and the risk of obesity, and genetic variants of APPL1 are
      associated with body fat distribution. However, the association between genetic
      variations of APPL2 and metabolic traits remains unknown. In the current study,
      we aimed to test the impacts of APPL2 genetic variants on obesity in a Chinese
      population with normal glucose tolerance. METHODS: We genotyped six single
      nucleotide polymorphisms (SNPs) in APPL2 in 1,808 non-diabetic subjects.
      Overweight and obesity were defined by body mass index (BMI). Obesity-related
      anthropometric parameters were measured, including height, weight, waist
      circumference, hip circumference. BMI and waist-hip ratio (WHR) were calculated.
      RESULTS: We found significant evidence of association with overweight/obesity for
      rs2272495 and rs1107756. rs2272495 C allele and rs1107756 T allele both conferred
      a higher risk of being overweight and obese (OR 1.218, 95% CI 1.047-1.416, p =
      0.011 for rs2272495; OR 1.166, 95% CI 1.014-1.341, p = 0.031 for rs1107756).
      After adjusting multiple comparisons, only the effect of rs2272495 on
      overweight/obesity remained to be significant (empirical p = 0.043). Moreover, we
      investigated the effects of these SNPs on obesity-related quantitative traits in
      all participants. rs2272495 was associated with BMI (p = 0.015), waist
      circumference (p = 0.006), hip circumference (p = 0.025) as well as WHR (p =
      0.047) under a recessive model. Similar associations were found for rs1107756
      except for WHR. CONCLUSION: This study suggests that genetic variations in APPL2
      are associated with overweight and obesity in Chinese population with normal
      glucose tolerance.

PMID- 22462605
TI  - Caudal vena cava kinking in dogs with ascites.
AB  - A 9-year-old dog with spontaneous ascites was found to have hepatic vein
      distension and a tortuous vena cava on abdominal ultrasound. In right lateral
      recumbency, the caudal vena cava crossed the diaphragm and became kinked before
      entering into the right atrium. Following this observation, we performed an
      experimental study in a normal dog to determine whether kinking of the caudal
      vena cava could be the result and not the cause of ascites. Ascites was induced
      using warm saline injected through a needle inserted into the abdominal cavity.
      Venograms were collected from different body positions, under four conditions:
      before and after a total of one, two and 3 liters of saline had been injected.
      Caudal vena cava kinking was observed in the experimental dog after 2 liters of
      fluid had been injected. Vena cava obstruction may cause ascites, but we found
      that sometimes caudal vena cava kinking can be the result and not the cause of
      the peritoneal effusion.

PMID- 22462606
TI  - pH control of intramolecular energy transfer and oxygen quenching in Ru(II)
      complexes having coupled electronic excited states.
AB  - This work illustrates the control of excited state energy transfer processes via
      variation of pH in transition metal complexes. In these systems a Ru(II) complex
      having two carboxylated bipyridyl ligands is covalently linked to pyrene via one
      of two different pyrene derivitized bipyridyl ligands. The energy of the Ru to
      carboxy-bipyridine (3)MLCT state is pH dependent while the pyrene triplet energy
      remains unchanged with solution acidity. At pH 0 the (3)MLCT state is the lowest
      energy state, and as the pH is raised and the carboxy-bipyridyl ligands are
      successively deprotonated, the energy of the (3)MLCT state rises above that of
      the pyrene triplet, resulting in a significant increase in the lifetime of the
      observed emission. Detailed analysis of ultrafast and microsecond time-resolved
      excited state decays result in a description of excited state decay that involves
      initial equilibration of the (3)MLCT and pyrene triplet states followed by
      relaxation to the ground state. The lifetime of excited state decay is defined by
      the position of the equilibrium, going from 2 MUs at pH 0 to >10 MUs at higher pH
      as the equilibrium favors the pyrene triplet. In addition, quenching of the
      excited state by dissolved oxygen exhibits a pH dependence that parallels that of
      the excited state lifetime. The results illustrate the utility of exploiting
      excited state equilibria of this type in the development of highly effective
      luminescent oxygen sensors.

PMID- 22462608
TI  - Pilot study for evidence-based nursing management: improving the levels of job
      satisfaction, organizational commitment, and intent to leave among nurses in
      Turkey.
AB  - Because of the nursing shortage problem, an important goal for nurse managers is
      preventing nurses from leaving the organization. This study analyzed the effect
      of evidence-based nursing management practices on nurses' levels of job
      satisfaction, organizational commitment, and intent to leave using the Promoting
      Action Research Implementation in Health Service framework as a guide. This study
      employed a single-group, quasi-experimental, pretest-post-test design with
      repeated measures. Data were collected using the Minnesota Job Satisfaction
      Questionnaire and the Organizational Commitment Scale. The study was conducted at
      a 127-bed private, accredited hospital. The sample was composed of 58 nurses who
      participated in all three measurements. Data analysis was conducted using
      repeated-measures anova and the Cochrane Q-test. An improvement was observed in
      the nurses' intrinsic, extrinsic, and total satisfaction levels, and in the
      degree of normative commitment. Nurse managers stated that they benefited from
      this study. In order to find effective and long-lasting solutions to the nursing
      shortage problem, evidence-based recommendations should be used in nursing
      management.

PMID- 22462607
TI  - Lymphocytic vasculitis of the prostate transition zone.
AB  - Study Type--Pathology (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? Lymphocytic vasculitis of the prostate is
      an exceedingly rare form of localised vasculitis that presents without systemic
      involvement, and is illustrated with anecdotal case reports; often as localised
      polyarteritis nodosa-like vasculitis. True incidence and clinical significance of
      lymphocytic vasculitis of the prostate in surgical specimens is virtually
      unknown. The present findings support that lymphocytic vasculitis of the prostate
      was present in 67 (12.4%) of 540 specimens. Lymphocytic vasculitis of the
      prostate was present in 14 (93.3%) of 15 specimens with prostatic infarction (P <
      0.001) with a risk of 124.68 (OR [odds ratio]; 95% CI [confidence interval] 16.07
      967.07) as compared with BPH cases not associated with lymphocytic vasculitis.
      OBJECTIVE: * To present our experience of lymphocytic vasculitis of the prostate
      in men with benign prostatic hyperplasia (BPH) without systemic involvement, as
      this is an exceedingly rare form of localised vasculitis and the incidence in
      surgical specimens and clinical significance of lymphocytic vasculitis is
      virtually unknown. PATIENTS AND METHODS: * A sequential cohort series of 540
      surgical specimens removed because of BPH-related symptoms, including simple
      prostatectomy (374 men) and transurethral resection of the prostate (166),
      comprised the study group. * All men had histological diagnosis of BPH and
      received surgical therapy only. None of the men had had previous surgery or
      granulomatous prostatitis. * The mean (range) age at diagnosis was 67.8 (38-89)
      years. RESULTS: * Lymphocytic vasculitis of the prostate was present in 67 (12.4
      %) of 540 specimens. It was seen in a variable number of small- to medium-sized
      parenchyma arteries with segmental to transmural lymphocytic inflammation, within
      the morphological spectrum of a polyarteritis nodosa (PAN)-like lesion seen at
      the periphery of BPH nodules. * In four cases, focal fibrinoid necrosis was seen
      in vessels with otherwise typical lymphocytic vasculitis features.
      Immunohistochemical staining showed a T cell predominant polymorphic cellular
      infiltrate with a minor component of B cells and monocytes. Six cases
      additionally had eosinophils (<1% of inflammatory cells). * Lymphocytic
      vasculitis of the prostate was present in 14 (93.3%) of 15 specimens with
      prostatic infarction (P < 0.001) with a risk of 124.68 (odds ratio [OR]; 95%
      confidence interval [CI] 16.07-967.07) as compared with BPH cases not associated
      with lymphocytic vasculitis. Logistic regression multivariate analysis selected
      both lymphocytic vasculitis of the prostate and patient age as significant
      predictors of prostate infarction with lymphocytic vasculitis being the most
      significant (P < 0.001; OR 128.12; 95% CI 16.298-1007.202). Follow-up information
      was available in all cases, range 2-16 years, and none of the patients developed
      systemic disease. * A validation set of 1665 additional cases including radical
      prostatectomy, cystoprostatectomy, and needle biopsies showed lymphocytic
      vasculitis of the prostate being associated to prostate infarction on univariate
      and multivariate logistic regression (P < 0.001; OR 228.34; 95% CI 45.17-1154.22)
      analyses. CONCLUSIONS: * Lymphocytic vasculitis in men with BPH is associated
      with prostatic infarction and should be considered a form of localised vasculitis
      with PAN-like morphology that does not necessitate additional evaluation for
      systemic disease. * The potential clinical relevance of lymphocytic vasculitis
      warrants further investigation.

PMID- 22462609
TI  - Molecular docking using the molecular lipophilicity potential as hydrophobic
      descriptor: impact on GOLD docking performance.
AB  - GOLD is a molecular docking software widely used in drug design. In the initial
      steps of docking, it creates a list of hydrophobic fitting points inside protein
      cavities that steer the positioning of ligand hydrophobic moieties. These points
      are generated based on the Lennard-Jones potential between a carbon probe and
      each atom of the residues delimitating the binding site. To thoroughly describe
      hydrophobic regions in protein pockets and properly guide ligand hydrophobic
      moieties toward favorable areas, an in-house tool, the MLP filter, was developed
      and herein applied. This strategy only retains GOLD hydrophobic fitting points
      that match the rigorous definition of hydrophobicity given by the molecular
      lipophilicity potential (MLP), a molecular interaction field that relies on an
      atomic fragmental system based on 1-octanol/water experimental partition
      coefficients (log P(oct)). MLP computations in the binding sites of
      crystallographic protein structures revealed that a significant number of points
      considered hydrophobic by GOLD were actually polar according to the MLP
      definition of hydrophobicity. To examine the impact of this new tool, ligand
      protein complexes from the Astex Diverse Set and the PDB bind core database were
      redocked with and without the use of the MLP filter. Reliable docking results
      were obtained by using the MLP filter that increased the quality of docking in
      nonpolar cavities and outperformed the standard GOLD docking approach.

PMID- 22462610
TI  - Stabilizing nanometer scale tip-to-substrate gaps in scanning electrochemical
      microscopy using an isothermal chamber for thermal drift suppression.
AB  - The control of a nanometer-wide gap between tip and substrate is critical for
      nanoscale applications of scanning electrochemical microscopy (SECM). Here, we
      demonstrate that the stability of the nanogap in ambient conditions is
      significantly compromised by the thermal expansion and contraction of components
      of an SECM stage upon a temperature change and can be dramatically improved by
      suppressing the thermal drift in a newly developed isothermal chamber. Air
      temperature in the chamber changes only at ~.2 mK/min to remarkably and
      reproducibly slow down the drift of tip-substrate distance to ~0.4 nm/min in
      contrast to 5-150 nm/min without the chamber. Eventually, the stability of the
      nanogap in the chamber is limited by its fluctuation with a standard deviation of
      +/-0.9 nm, which is mainly ascribed to the instability of a piezoelectric
      positioner. The subnanometer scale drift and fluctuation are measured by forming
      a ~20 nm-wide gap under the 12 nm-radius nanopipet tip based on ion transfer at
      the liquid/liquid interface. The isothermal chamber is useful for SECM and,
      potentially, for other scanning probe microscopes, where thermal-drift errors in
      vertical and lateral probe positioning are unavoidable by the feedback-control of
      the probe-substrate distance.

PMID- 22462612
TI  - Biscyclometalated ruthenium complexes bridged by 3,3',5,5'-tetrakis(N
      methylbenzimidazol-2-yl)biphenyl: synthesis and spectroscopic and electronic
      coupling studies.
AB  - A series of biscyclometalated ruthenium complexes bridged by the title ligand
      were prepared by either an oxidative dimerization of corresponding monometallic
      complexes or treatment of the bridging ligand with Ru(L)Cl(3) (L = capping
      ligand). The electronic properties of these complexes were examined by
      electrochemical and spectroscopic analysis and DFT/TDDFT calculations. The degree
      of metal-metal electronic coupling of these complexes was estimated on the basis
      of intervalence charge-transfer transition analysis of corresponding mixed-valent
      complexes. These studies indicated that the electronic coupling was strongly
      dependent on the electronic nature of the terminal ligands. A hole-transfer
      superexchange mechanism was used to understand the underlying electron-transfer
      processes.

PMID- 22462611
TI  - Deoxyribonucleoside kinases in two aquatic bacteria with high specificity for
      thymidine and deoxyadenosine.
AB  - Deoxyribonucleoside kinases (dNKs) are essential in the mammalian cell but their
      'importance' in bacteria, especially aquatic ones, is less clear. We studied two
      aquatic bacteria, Gram-negative Flavobacterium psychrophilum JIP02/86 and
      Polaribacter sp. MED152, for their ability to salvage deoxyribonucleosides (dNs).
      Both had a Gram-positive-type thymidine kinase (TK1), which could phosphorylate
      thymidine, and one non-TK1 dNK, which could efficiently phosphorylate
      deoxyadenosine and slightly also deoxycytosine. Surprisingly, the four tested
      dNKs could not phosphorylate deoxyguanosine, and apparently, these two bacteria
      are missing this activity. When tens of available aquatic bacteria genomes were
      examined for the presence of dNKs, a majority had at least a TK1-like gene, but
      several lacked any dNKs. Apparently, among aquatic bacteria, the role of the dN
      salvage varies.

PMID- 22462613
TI  - Rituximab in treatment of primary gastric diffuse large B-cell lymphoma.
AB  - In the rituximab era, the optimal treatment modality for primary gastric diffuse
      large B-cell lymphoma (PG-DLBCL) still remains unclear. We performed a
      retrospective, multicenter analysis of 65 patients with PG-DLBCL to assess the
      efficacy and toxicity of the addition of rituximab to conventional chemotherapy.
      When compared with conventional chemotherapy, there was a trend that rituximab
      plus chemotherapy yielded a higher complete response rate, 5-year event-free
      survival (EFS) rate and 5-year overall survival (OS) rate, but this was not
      statistically significant. In subgroup analysis, better OS was observed only for
      patients with advanced-stage disease when rituximab was added. When involved
      field radiotherapy (IFRT) was included, EFS and OS were significantly prolonged
      in the conventional chemotherapy group, but not in the immunochemotherapy group.
      If focusing on patients with localized-stage disease receiving
      immunochemotherapy, the efficacies of short-course rituximab (R)-chemotherapy
      plus IFRT and 6-8 courses of R-chemotherapy without IFRT were comparable. In
      conclusion, it is necessary to carry out prospective randomized trials to help
      further illuminate the role of rituximab in the PG-DLBCL treatment landscape. If
      a patient has been treated with a non-rituximab-containing regimen, additional
      IFRT should be considered, and for patients with advanced-stage disease,
      rituximab should be considered.

PMID- 22462614
TI  - Imatinib-induced aplastic anemia in a patient with chronic myeloid leukemia.

PMID- 22462615
TI  - Elevated lactate dehydrogenase levels detected during routine follow-up do not
      predict relapse in patients with diffuse large B-cell lymphoma who achieve
      complete remission after primary treatment with rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisone-like immunochemotherapy.
AB  - A significant minority of patients with diffuse large B-cell lymphoma (DLBCL) who
      enter a complete remission following standard first-line immunochemotherapy will
      relapse. A primary aim of follow-up is to detect early relapse, with the hope of
      improving outcome following salvage chemotherapy. It is often routine to measure
      lactate dehydrogenase (LDH) as part of follow-up; however, the evidence for the
      utility of LDH as a predictor for relapse is scant. A retrospective analysis of
      the LDH results recorded during the follow-up of 102 patients with DLBCL who
      achieved a CR following treatment was undertaken in order to determine the
      utility of LDH as a predictor for relapse (median follow-up 24 months). Despite
      the fact that the sensitivity of LDH was 69% (95% confidence interval [CI] 39
      91), the positive predictive value (PPV) of a raised LDH was only 9/63, 14% (95%
      CI 6.7-25). Furthermore, in eight of the nine patients who had a raised LDH prior
      to relapse, symptoms suggestive of relapse were documented simultaneously. As the
      PPV of a raised LDH is so low and because a raised LDH may cause unnecessary
      worry, leading to unnecessary radiological investigations, routine evaluation of
      LDH in patients with DLBCL who achieve CR and who are asymptomatic is not
      recommended.

PMID- 22462616
TI  - Contribution of PD-L1 to oncogenesis of lymphoma and its RNAi-based targeting
      therapy.
AB  - Lymphomas are common malignancies that are prevalent worldwide. In recent years,
      some types of lymphoma have become curable, but relapsed and refractory lymphomas
      remain common and challenging. Impaired host immunity and therapeutic resistance
      are thought to play pivotal roles in the pathogenesis and progression of
      lymphomas. PD-L1 (programmed death ligand 1) is a newly discovered member of the
      B7 family of molecules, and its receptor is PD-1. It is known that the
      costimulatory signal of PD-1 and PD-L1 can help tumor escape from cellular
      immunity. However, little is known of the impact of PD-L1 on tumor cells,
      especially lymphomas. Our investigation shows for the first time that: (1) PD-L1
      has a vital role in lymphoma oncogenesis; (2) the down-regulation of PD-L1
      combined with chemotherapy can significantly suppress lymphoma growth, promote
      antitumor activity and prolong the survival rate; and (3) targeted therapy of PD
      L1 may provide a new and promising approach to the treatment of lymphomas.

PMID- 22462617
TI  - Smoking and lymphoma: a small part of a complex story.

PMID- 22462618
TI  - Influence of charge on anion receptivity in amide-based macrocycles.
AB  - Binding and structural aspects of anions with tetraamido/diquaternized diamino
      macrocyclic receptors containing m-xylyl, pyridine, and thiophene spacers are
      reported. (1)H NMR studies indicate that the quaternized receptors display higher
      affinities for anions compared to corresponding neutral macrocycles. The
      macrocycles containing pyridine spacers consistently display higher affinity for
      a given anion compared to those with either m-xylyl or thiophene spacers. The m
      xylyl- and pyridine-containing receptors exhibit high selectivity for H(2)PO(4)(
      ) in DMSO-d(6) with association constants, K(a) = 1.09 * 10(4) and >10(5) M(-1),
      respectively, and moderate selectivity for Cl(-) with K(a) = 1.70 * 10(3) and
      5.62 * 10(4) M(-1), respectively. Crystallographic studies for the Cl(-) and
      HSO(4)(-) complexes indicate that the m-xylyl-containing ligand is relatively
      elliptical in shape, with the two charges at ends of the major axis of the
      ellipse. The anions are hydrogen bonded with the macrocycle but are outside the
      ligand cavity. In the solid state, an unusual low-barrier hydrogen bond (LBHB)
      was discovered between two of the macrocycle's carbonyl oxygen atoms in the
      HSO(4)(-) complex. The pyridine-containing macrocycle folds so that the two
      pyridine units are face-to-face. The two I(-) ions are chelated to the two amides
      adjacent to a given pyridine. In the structure of the thiophene containing
      macrocycle with two BPh(4)(-) counterions, virtually no interaction was observed
      crystallographically between the macrocycle and the bulky anions.

PMID- 22462619
TI  - C-reactive protein and seizures in focal epilepsy: a video
      electroencephalographic study.
AB  - PURPOSE:   C-reactive protein (CRP) has been studied extensively in many
      noninflammatory neurologic conditions, but there has been little study of CRP in
      the context of seizures or epilepsy. The purpose of this study was to examine CRP
      concentrations in patients with refractory focal epilepsy who were undergoing
      video-electroencephalography (EEG) monitoring compared with healthy controls, and
      CRP change during 24 h after a seizure. METHODS:   CRP levels were measured in
      serum at the onset of video-EEG recording (CRP-0h) and at 3, 6, 12, and 24 h
      after index seizure (the first verified localized-onset seizure) in 31 patients
      during inpatient video-EEG monitoring by using high sensitivity measurement of
      CRP concentration. The patients were categorized into two groups: temporal lobe
      epilepsy (TLE; n = 15) and extratemporal lobe epilepsy (XLE; n = 16). Eighty
      healthy volunteers served as controls. KEY FINDINGS:   CRP-0h concentration was
      significantly higher in patients with refractory focal epilepsy than in controls
      (3.5 vs. 0.7 mg/ml, p < 0.001). All five patients with elevated CRP-0h (>mean + 2
      standard deviations in controls) had TLE (vs. none in XLE; p = 0.018). Index
      seizure type was associated with CRP increase from baseline to maximum level
      after index seizure (p = 0.005). The most important predictor of increase in CRP
      level was secondarily generalized tonic-clonic seizure (SGTCS; p = 0.030).
      SIGNIFICANCE:   The higher baseline levels in patients with epilepsy compared
      with healthy controls demonstrates that CRP concentrations are also affected in
      refractory epilepsy. Our data suggest that SGTCS stimulates CRP production. These
      results emphasize the association between inflammation and refractory epilepsy.

PMID- 22462621
TI  - Stable isotope deltas: tiny, yet robust signatures in nature.
AB  - Although most of them are relatively small, stable isotope deltas of naturally
      occurring substances are robust and enable workers in anthropology, atmospheric
      sciences, biology, chemistry, environmental sciences, food and drug
      authentication, forensic science, geochemistry, geology, oceanography, and
      paleoclimatology to study a variety of topics. Two fundamental processes explain
      the stable isotope deltas measured in most terrestrial systems: isotopic
      fractionation and isotope mixing. Isotopic fractionation is the result of
      equilibrium or kinetic physicochemical processes that fractionate isotopes
      because of small differences in physical or chemical properties of molecular
      species having different isotopes. It is shown that the mixing of radioactive and
      stable isotope end members can be modelled to provide information on many natural
      processes, including (14)C abundances in the modern atmosphere and the stable
      hydrogen and oxygen isotopic compositions of the oceans during glacial and
      interglacial times. The calculation of mixing fractions using isotope balance
      equations with isotope deltas can be substantially in error when substances with
      high concentrations of heavy isotopes (e.g. (13)C, (2)H, and (18)O ) are mixed.
      In such cases, calculations using mole fractions are preferred as they produce
      accurate mixing fractions. Isotope deltas are dimensionless quantities. In the
      International System of Units (SI), these quantities have the unit 1 and the
      usual list of prefixes is not applicable. To overcome traditional limitations
      with expressing orders of magnitude differences in isotope deltas, we propose the
      term urey (symbol Ur), after Harold C. Urey, for the unit 1. In such a manner, an
      isotope delta value expressed traditionally as-25 per mil can be written as-25
      mUr (or-2.5 cUr or-0.25 dUr; the use of any SI prefix is possible). Likewise,
      very small isotopic differences often expressed in per meg 'units' are easily
      included (e.g. either+0.015 0/00 or+15 per meg can be written as+15 MUUr.

PMID- 22462623
TI  - Dielectrophoretic cell capture on polyester membranes.
AB  - A new system for dielectrophoretic cell capture on permeable polyester membranes
      is presented. Conventional photolithographic techniques were used to fabricate
      gold microelectrodes on a polyester membrane. The characterization of the
      microelectrodes showed that there were no differences regarding roughness,
      permeability, and hydrophilicity of the membrane before and after processing.
      Finally, dielectrophoretic cell capture and viability in a microfluidic device
      was demonstrated on the patterned membrane. These membranes could ultimately be
      combined with multilayer microfluidic devices to form a powerful tool for studies
      of cell-cell interactions in coculture, whereby spatial separation of different
      cell types and/or microenvironments are required.

PMID- 22462622
TI  - Sex enhances adaptation by unlinking beneficial from detrimental mutations in
      experimental yeast populations.
AB  - BACKGROUND: The maintenance of sexuality is a classic problem in evolutionary
      biology because it is a less efficient mode of reproduction compared with
      asexuality; however, many organisms are sexual. Theoretical work suggests sex
      facilitates natural selection, and experimental data support this. However, there
      are fewer experimental studies that have attempted to determine the mechanisms
      underlying the advantage of sex. Two main classes of hypotheses have been
      proposed to explain its advantage: detrimental mutation clearance and beneficial
      mutation accumulation. Here we attempt to experimentally differentiate between
      these two classes by evolving Saccharomyces cerevisiae populations that differ
      only in their ability to undergo sex, and also manipulate mutation rate. We
      cannot manipulate the types of mutation that occur, but instead propagate
      populations in both stressful and permissive environments and assume that the
      extent of detrimental mutation clearance and beneficial mutation incorporation
      differs between them. RESULTS: After 300 mitotic generations interspersed with 11
      rounds of sex we found there was no change or difference in fitness between
      sexuals and asexuals propagated in the permissive environment, regardless of
      mutation rate. Sex conferred a greater extent of adaptation in the stressful
      environment, and wild-type and elevated mutation rate sexual populations adapted
      equivalently. However, the asexual populations with an elevated mutation rate
      appeared more retarded in their extent of adaptation compared to asexual wild
      type populations. CONCLUSIONS: Sex provided no advantage in the permissive
      environment where beneficial mutations were rare. We could not evaluate if sex
      functioned to clear detrimental mutations more effectively or not here as no
      additional fitness load was observed in the mutator populations. However, in the
      stressful environment, where detrimental mutations were likely of more
      consequence, and where beneficial mutations were apparent, sex provided an
      advantage. In the stressful environment asexuals were increasingly constrained in
      their extent of adaptation with increasing mutation rate. Sex appeared to
      facilitate adaptation not just by more rapidly combining beneficial mutations,
      but also by unlinking beneficial from detrimental mutations: sex allowed
      selection to operate on both types of mutations more effectively compared to
      asexual populations.

PMID- 22462624
TI  - Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and
      pathophysiology.
AB  - Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is a protein with several
      suggested functions. Although the first discovery of this molecule as a pre-B
      cell colony-enhancing factor suggested primarily a cytokine function, its
      rediscovery as the key enzyme in nicotinamide adenine dinucleotide generation has
      considerably widened its potential biological activities. Although originally
      thought to be produced in adipose tissue (i.e., adipocytes and infiltrating
      macrophages), its production seems to involve other cells and tissues such as
      skeletal muscle, liver, immune cells, cardiomyocytes, and the brain.
      Visfatin/NAMPT has both intracellular and extracellular effects influencing
      several signaling pathways. Its broad spectrum of effects is mirrored by its
      potential involvement in a wide range of disorders including human
      immunodeficiency virus infection, septicemia, myocardial failure,
      atherosclerosis, metabolic disorders, inflammatory diseases, malignancies, and
      neurodegenerative disorders and aging. Moreover, studies on visfatin/NAMPT in
      atherosclerotic disorders suggest a rather complex role of this molecule in
      pathophysiology, potentially mediating both adaptive and maladaptive responses.

PMID- 22462625
TI  - Probing at implants with peri-implantitis and its relation to clinical peri
      implant bone loss.
AB  - OBJECTIVES: To evaluate the probing depth at implants with signs of peri
      implantitis before and following the removal of the prosthetic reconstructions
      and its relation with the peri-implant bone level as revealed by open access flap
      surgery. MATERIAL AND METHODS: Twenty-nine patients with 89 implants with
      diagnosis of peri-implantitis were included in the study. The probing pocket
      depth at implants before (PPD-1) and following (PPD-2) the removal of the
      prosthetic reconstructions was measured at four sites of the implants. These
      measurements were also analysed in relation to the amount of peri-implant bone
      loss measured during peri-implant surgery. RESULTS: The results showed that in
      only 119 (37%) of the sites, the measurements were similar between PPD-1 and PPD
      2; in 124 sites (39%), the difference was +/-1 mm, in 47 sites (15%) it was +/-2
      mm and in the rest of the sites it was +/-3 mm. A high linear and statistically
      significant (P = <0.001) correlation between PPD-2 and the bone loss measured at
      implants for all and single surfaces was observed (r = 0.67, range 0.64-0.69),
      while PPD-1 yielded a weak and no statistically significant correlation (r =
      0.35, range 0.27-0.42). The analysis of the bone loss at implants showed that 59
      implants (66%) had an amount of bone loss that was similar at all the four
      surfaces, while in 30 implants, the bone loss differed for the various sites. A
      higher extent of bone loss was often detected at the buccal compared with the
      other sites. CONCLUSION: The results of this study yielded differences in the
      pocket probing measurements at implants with or without the prosthetic
      reconstruction in place and that the probing pocket depth following the removal
      of the prosthesis had a high correlation with the amount of bone loss at implants
      assessed during surgery.

PMID- 22462626
TI  - Increasing the dose of vardenafil on a daily basis does not improve erectile
      function after unilateral nerve-sparing radical prostatectomy.
AB  - INTRODUCTION: Several treatment regimens for rehabilitation of erectile function
      (EF) after nerve-sparing radical prostatectomy (nsRP) are currently discussed.
      The optimal and most cost-effective therapy is still not found yet. AIM: To
      evaluate the effect of vardenafil, a PDE5 inhibitor, dose escalation on recovery
      of EF after unilateral nsRP. METHODS: Thirty-six sexually active patients
      received a unilateral nsRP. All patients completed an International Index of
      Erectile Function-5 items (IIEF-5) questionnaire concerning EF preoperatively.
      Group 1 (N = 12 patients) received vardenafil 5 mg/day vs. group 2 (N = 12) who
      received vardenafil 10 mg/day at night beginning the day of catheter removal. A
      control of 12 patients underwent follow-up without PDE5 inhibitors. MAIN OUTCOME
      MEASURE: The IIEF-5 was the primary end point. IIEF-5 questionnaires were
      completed at baseline, 3, 6, and 12 months after nsRP. RESULTS: In group 1 (5
      mg/day vardenafil) the IIEF-5 score decreased from a preoperative 22.4 mean score
      to 4.2 at 3 months, 8.9 at 6 months, and 13.4 mean score at 12 months after nsRP
      vs. preoperative 22.8, 4.1 at 3 months, 7.9 at 6 months, and 12.8 mean score at
      12 months in group 2 (10 mg/day vardenafil). In the control group the
      preoperative IIEF-5 mean score of 21.9 decreased to 3.8 at 3 months, 6.1 at 6
      months, and 8.9 at 12 months. Statistical evaluation showed significant
      difference in IIEF-5 score and time to recovery of EF between groups 1 and 3 and
      between groups 2 and 3 (P < 0.01). No statistical differences were found between
      groups 1 and 2. CONCLUSIONS: Daily low-dose vardenafil lead to significant
      improvement of recovery of EF. In this study doubling the dosage did not improve
      the recovery of EF further.

PMID- 22462627
TI  - Aspirin for primary prevention of cardiovascular events in the elderly: current
      status and future directions.
AB  - The role of aspirin in the secondary prevention of occlusive cardiovascular
      events has now been well established. Given this, aspirin in primary prevention
      has been the focus of several large trials and subsequent meta-analyses over the
      past 3 decades, and yet the issue remains controversial. Recent studies in
      populations with high baseline risk - such as diabetics and those with
      asymptomatic peripheral arterial disease - have not found the expected benefits
      of aspirin on cardiovascular endpoints, which contrasts with earlier studies that
      reported a reduced relative risk for outcomes such as myocardial infarction and
      ischaemic stroke, but not for mortality. Furthermore, in healthy populations, the
      absolute risk reduction conferred by aspirin is small and needs to be balanced
      against the risk of a major haemorrhage. Older adults have a higher risk for
      cardiovascular events and therefore might represent the group in which aspirin
      for primary prevention could deliver the greatest absolute benefit, yet at the
      same time, the elderly bear an increased vulnerability to major haemorrhage,
      including haemorrhagic stroke. It is also not known whether older adults
      experience the same risk reduction from aspirin as middle-aged individuals. The
      current evidence base does not sufficiently clarify whether aspirin for primary
      prevention confers a meaningful net benefit in the elderly.

PMID- 22462629
TI  - The effect of cognitive impairment in the elderly on the initial and long-term
      stability of warfarin therapy.
AB  - BACKGROUND: Despite guidelines that clearly outline the benefits of warfarin, it
      remains underutilized. Various reasons are associated with the underuse of
      warfarin; however, cognitive impairment (CI) has been identified as one of the
      most common causes for not electing to anticoagulate elderly patients with atrial
      fibrillation. Nevertheless, there are limited data on warfarin use in such
      patients; therefore, we investigated anticoagulation stability in patients with
      and without CI. OBJECTIVES: Our objectives were to (i) examine if mild to
      moderate CI delayed the time required to achieve initial therapeutic
      anticoagulation; (ii) determine if mild to moderate CI was associated with long
      term anticoagulation instability; and (iii) assess if initial anticoagulation
      problems predicted long-term anticoagulation instability. METHODS: A
      retrospective study in a pharmacist-managed anticoagulation clinic was conducted
      in community-dwelling patients >=60 years of age on warfarin therapy with a
      target international normalized ratio (INR) of 2.0-3.0. Our study included 57
      patients; 20 were initiated on warfarin and 54 were analysed for long-term
      anticoagulation stability. Age, ethnicity, gender, warfarin indication, co
      morbidities and caregiver involvement were recorded. We defined CI as having a
      Mini-Mental State Examination (MMSE) score of <=26. To evaluate initial
      anticoagulation stability between groups, we analysed (i) number of clinic visits
      and days to achieve therapeutic INR; and (ii) minor and major adverse events upon
      initiation of warfarin. To evaluate long-term anticoagulation stability, we
      analysed (i) time in therapeutic range (TTR); (ii) the percentage of clinic
      visits with a reported dose mishap and the frequency of out-of-range INRs
      resulting from dose mishaps; and (iii) parameters associated with the intensity
      of clinic management: weekly warfarin dose changes, transient dose adjustments,
      any dose manipulation and the length of time between clinic visits. RESULTS: We
      found no difference in the number (mean +/- SD) of visits (control = 5.8 +/- 4.3,
      CI = 4.6 +/- 2.4; p = 0.44) or days (control = 51.6 +/- 45.7, CI = 35.8 +/- 30.5;
      p = 0.36) required to achieve initial therapeutic anticoagulation. No adverse
      effects were reported in either group. In terms of long-term stability, TTR (mean
      +/- SD) was similar for both groups (control = 65 +/- 20% vs CI = 61 +/- 16%; p =
      0.36). Although the proportion of dose mishaps did not differ (control = 74 in
      705 visits, CI = 86 in 691 visits; p = 0.18), dose mishaps resulted in a greater
      frequency of out-of-range INRs for patients with CI (p = 0.01). There were no
      differences in clinic management measures between groups (p = not statistically
      significant [NS] for all). Finally, we found no correlation between the time to
      reach initial anticoagulation stability and long-term stability for either group
      (p = NS for all). CONCLUSION: We found mild to moderate CI neither delayed the
      time required to achieve therapeutic anticoagulation, nor decreased
      anticoagulation stability versus patients with normal cognitive function.
      Additionally, CI did not require more intensive clinic management. CI should not
      necessarily be a barrier to the use of warfarin anticoagulation in elderly
      patients attending an anticoagulation clinic.

PMID- 22462628
TI  - Management of pain in the elderly at the end of life.
AB  - Pain is one of the symptoms most frequently encountered in elderly patients at
      the end of life. The management of pain in the elderly in general has been
      associated with undertreatment. The geriatric population has been identified as a
      challenging population with respect to pain management because of issues related
      to co-morbidities, polypharmacy and cognitive dysfunction. In the geriatric
      population, the assessment of pain requires measurement of pain intensity,
      delineation of opioid responsiveness, and clarification of the impact of pain on
      patients' psychological, social, spiritual and existential domains. Effective
      pain management is guided by the World Health Organization (WHO) analgesic
      stepladder, which categorizes pain intensity according to severity and recommends
      analgesic agents based on their strength and works effectively in the elderly
      patient population. Step 1 is reserved for mild pain. Patients in this category
      are treated with nonopioid analgesics such as acetaminophen, or a nonsteroidal
      anti-inflammatory, with consideration of an adjuvant analgesic if necessary. Step
      2 is reserved for patients experiencing mild to moderate pain who are already
      taking a nonopioid analgesic, with or without an adjuvant analgesic, but are
      still experiencing poor analgesic control. Step 2 agents include acetaminophen
      products containing hydrocodone, oxycodone, codeine and tramadol. Patients with
      moderate to severe pain require strong analgesics belonging to step 3 of the WHO
      analgesic stepladder. Step 3 opioids include morphine, hydromorphone, fentanyl,
      levorphanol, methadone and oxycodone. Familiarity with opioid pharmacokinetics,
      equianalgesic dosing and adverse effects is necessary for the safe and effective
      use of these drugs. The appropriate use of adjuvant analgesics such as
      antiepileptic drugs, antidepressants and local anaesthetics can enhance the use
      of opioids, especially in cases where opioid responsiveness may be in question,
      such as with neuropathic pain. This paper will provide an overview of the
      analgesic considerations for elderly patients at the end of life.

PMID- 22462630
TI  - Quality measures for medication continuity in long-term care facilities, using a
      structured panel process.
AB  - BACKGROUND: Patient transitions, such as transfers between acute and long-term
      care (LTC), aposare times when the likelihood of communication failure between
      healthcare providers is increased. Employing appropriate health quality
      indicators helps support improvement efforts. To date, few quality indicators
      that evaluate the continuity of medication use between acute and LTC facilities
      have been described. OBJECTIVE: The aim of the study was to develop quality
      indicators signalling the potential discontinuation of previously prescribed
      medications for chronic diseases when residents return to LTC following an acute
      care hospitalization. METHODS: A literature review for the selection of potential
      indicators was conducted, followed by a three-step process: (i) initial screening
      round that rated the indicators; (ii) a 1-day in-person consensus meeting in
      which the panel refined the parameters regarding the proposed quality indicators;
      and (iii) a final anonymous survey that assessed consensus among panel members.
      The study setting was a survey and consensus meeting with national
      representation, held in Toronto, ON, Canada. A ten-member expert panel with broad
      geographical and clinical representation participated and was made up of
      registered nurses, physicians, pharmacists, policy makers and academic
      researchers. A 75% agreement threshold was required for consensus, as measured on
      a 9-point Likert-type scale. The panel evaluated quality indicators for
      effectiveness, relevance and feasibility, using currently available healthcare
      administrative data. RESULTS: The panel reached consensus on four quality
      indicators to assess the unintentional discontinuation of medications prescribed
      to LTC residents for chronic diseases upon return to LTC after an acute-care
      admission. The selected indicators were (i) HMG-CoA reductase inhibitors
      (statins) for all indications; (ii) anticoagulants (e.g. warfarin) for the
      indication of atrial fibrillation; (iii) proton-pump inhibitors for the
      indication of post-gastrointestinal haemorrhage; and (iv) thyroxine for all
      indications. The panel identified three additional treatment groups for future
      consideration as quality indicators: anti-Parkinson's disease, anti-diabetes and
      antidepressant medications. CONCLUSION: A novel set of quality indicators has
      been developed to evaluate medication continuity between acute and LTC
      facilities. The adoption and implementation of these indicators in clinical
      practice can help inform quality improvement efforts at various local and
      regional levels.

PMID- 22462631
TI  - Bazedoxifene: a guide to its use in postmenopausal osteoporosis.
AB  - Oral bazedoxifene (Conbriza(r)) reduces the incidence of new vertebral fractures
      in patients with postmenopausal osteoporosis. It also appears to reduce the risk
      of nonvertebral fractures in high-risk patients. Bazedoxifene is generally well
      tolerated and does not appear to have detrimental effects on endometrial or
      breast tissue.

PMID- 22462632
TI  - Peculiar mechanism of solubilization of a sparingly water soluble drug into
      polymeric micelles. Kinetic and equilibrium studies.
AB  - Complementary kinetic and equilibrium studies on the solubilization process of
      the sparingly water soluble tamoxifen (TAM) drug in polymeric aqueous solutions
      have been performed by using the spectrophotometric method. In particular, the
      amphiphilic copolymers obtained by derivatization of polymeric chain of poly(N-2
      hydroxyethyl)-dl-aspartamide, PHEA, with poly(ethylene glycol)s, PEG (2000 or
      5000 Da), and/or hexadecylamine chain, C16, namely PHEA-PEG2000-C16, PHEA-PEG5000
      C16, PHEA-C16, have been employed. Preliminary to the kinetic and equilibrium
      data quantitative treatment, the molar absorption coefficient of TAM in polymeric
      micelle aqueous solution has been determined. By these studies the solubization
      sites of TAM into the polymeric micelles have been determined and the
      solubilization mechanism has been elucidated through a nonconventional approach
      by considering the TAM partitioned between three pseudophases, i.e., the aqueous
      pseudophase, the hydrophilic corona, and the hydrophobic core. The simultaneous
      solution of the rate laws associated with each step of the proposed mechanism
      allowed the calculation of the rate constants associated with the involved
      processes, the values of which are independent of both the copolymer
      concentration and nature, with the exception of the rate of the TAM transfer from
      the corona to the core. This has been attributed to the steric barrier,
      represented by the corona, which hampers the solubilization into the core. The
      binding constant values of the TAM to the hydrophilic corona of the polymeric
      micelles, calculated through the quantitative analysis of the equilibrium data,
      depend on the thickness of the hydrophilic headgroup, while those of the
      hydrophobic core are almost independent of the copolymer type. Further
      confirmation to the proposed solubilization mechanism has been provided by
      performing the kinetic and equilibrium measurements in the presence of PHEA
      PEG2000 and PHEA-PEG5000 copolymers. 

PMID- 22462633
TI  - Characterization of glycine-rich RNA-binding proteins in Brassica napus under
      stress conditions.
AB  - Although the functional roles of glycine-rich RNA-binding proteins (GRPs) during
      stress adaptation have been extensively evaluated in Arabidopsis thaliana and
      rice (Oryza sativa), the stress-responsive roles of a majority of GRPs have not
      been characterized in other plant species including rapeseed (Brassica napus).
      Here, the characteristic features and stress-responsive expression patterns of
      GRPs in B. napus (BnGRPs) were investigated. The genome of B. napus contains
      seven closely related BnGRPs, where the amino acid sequences of a well-conserved
      RNA-recognition motif at the N-terminal region are highly similar to each other
      but the sequences of the C-terminal glycine-rich region vary greatly among
      different BnGRPs. The transcript levels of all BnGRPs were markedly upregulated
      by cold stress, while their expression was significantly downregulated by
      dehydration or high salinity stress. Among the seven BnGRPs evaluated, BnGRP1 was
      characterized in more detail for its cellular localization and functional role as
      an RNA chaperone under cold stress. Cold-induced BnGRP1 successfully complemented
      the cold-sensitive phenotype of Escherichia coli mutant BX04 cells under cold
      stress, and harbored DNA- and RNA-melting abilities. Ectopic expression of BnGRP1
      in Arabidopsis resulted in accelerated seed germination and enhanced freezing
      tolerance of the plant under cold or freezing stress. Collectively, the results
      of this study support the emerging idea that GRPs are functionally conserved RNA
      chaperones during the cold adaptation process in diverse plant species.

PMID- 22462634
TI  - Axial forces and bending moments in the loaded rabbit tibia in vivo.
AB  - BACKGROUND: Different animal models are used as fracture models in orthopaedic
      research prior to implant use in humans, although biomechanical forces can differ
      to a great extend between species due to variable anatomic conditions,
      particularly with regard to the gait. The rabbit is an often used fracture model,
      but biomechanical data are very rare. The objective of the present study was to
      measure axial forces, bending moments, and bending axis directly in the rabbit
      tibia in vivo. The following hypothesis was tested: Axial forces and bending
      moments in the mid-diaphysis of rabbit tibia differ from other experimental
      animals or indirectly calculated data. METHODS: A minifixateur system with 4
      force sensors was developed and attached to rabbit tibia (n = 4), which were
      subsequently ostectomised. Axial forces, bending moments and bending angles were
      calculated telemetrically during weight bearing in motion between 6 and 42 days
      post operation. RESULTS: Highest single values were 201% body weight [% bw] for
      axial forces and 409% bw cm for bending moments. Whereas there was a continous
      decrease in axial forces over time after day 10 (P = 0.03 on day 15), a decrease
      in bending moments was inconsistent (P = 0.03 on day 27). High values for bending
      moments were frequently, but not consistently, associated with high values for
      axial forces. CONCLUSION: Axial forces in rabbit tibia exceeded axial forces in
      sheep, and differed from indirectly calculated data. The rabbit is an appropriate
      fracture model because axial loads and bending moments in rabbit tibia were more
      closely to human conditions than in sheep tibia as an animal model.

PMID- 22462635
TI  - The effect of bone marrow microenvironment on the functional properties of the
      therapeutic bone marrow-derived cells in patients with acute myocardial
      infarction.
AB  - BACKGROUND: Treatment of acute myocardial infarction with stem cell
      transplantation has achieved beneficial effects in many clinical trials. The bone
      marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients
      has never been studied even though myocardial infarction is known to cause an
      imbalance in the acid-base status of these patients. The aim of this study was to
      assess if the blood gas levels in the bone marrow of STEMI patients affect the
      characteristics of the bone marrow cells (BMCs) and, furthermore, do they
      influence the change in cardiac function after autologous BMC transplantation.
      The arterial, venous and bone marrow blood gas concentrations were also compared.
      METHODS: Blood gas analysis of the bone marrow aspirate and peripheral blood was
      performed for 27 STEMI patients receiving autologous stem cell therapy after
      percutaneous coronary intervention. Cells from the bone marrow aspirate were
      further cultured and the bone marrow mesenchymal stem cell (MSC) proliferation
      rate was determined by MTT assay and the MSC osteogenic differentiation capacity
      by alkaline phosphatase (ALP) activity assay. All the patients underwent a 2D
      echocardiography at baseline and 4 months after STEMI. RESULTS: As expected, the
      levels of pO(2), pCO(2), base excess and HCO(3) were similar in venous blood and
      bone marrow. Surprisingly, bone marrow showed significantly lower pH and Na(+)
      and elevated K(+) levels compared to arterial and venous blood. There was a
      positive correlation between the bone marrow pCO(2) and HCO(3) levels and MSC
      osteogenic differentiation capacity. In contrast, bone marrow pCO(2) and HCO(3)
      levels displayed a negative correlation with the proliferation rate of MSCs.
      Patients with the HCO(3) level below the median value exhibited a more marked
      change in LVEF after BMC treatment than patients with HCO(3) level above the
      median (11.13 +/- 8.07% vs. 2.67 +/- 11.89%, P = 0.014). CONCLUSIONS: Low bone
      marrow pCO(2) and HCO(3) levels may represent the optimal environment for BMCs in
      terms of their efficacy in autologous stem cell therapy in STEMI patients.

PMID- 22462636
TI  - Appetite regulation in response to sitting and energy imbalance.
AB  - The impact of sitting and energy imbalance on appetite and appetite-regulating
      hormones (acylated ghrelin and leptin) was assessed in response to 1 day of
      sitting, with and without changes in energy intake. Fourteen men and women
      completed each of three 24-h conditions: high energy expenditure (standing) with
      energy balance (STAND), low energy expenditure (sitting) with energy surplus
      (SIT), and sitting with energy balance (SIT-BAL). Ghrelin, leptin, and appetite
      were measured in the fasted state and following a standardized meal. In the
      fasted state, there were no differences among conditions. Following the meal,
      ghrelin was lower in SIT than in STAND, with no change in appetite. When intake
      was reduced (SIT-BAL), the decrease in ghrelin when sitting was attenuated,
      hunger increased, and fullness decreased. SIT led to lower ghrelin concentrations
      in the men, whereas in the women, leptin increased. SIT-BAL led to an increase in
      ghrelin in the men but attenuated the leptin response, reduced ghrelin, increased
      hunger, and decreased fullness in the women. Because a dramatic reduction in
      energy expenditure was not accompanied by reduced appetite, prolonged sitting may
      promote excess energy intake, leading to weight gain in both men and women.

PMID- 22462637
TI  - A mutation at IVS1 + 5 of the von Hippel-Lindau gene resulting in intron
      retention in transcripts is not pathogenic in a patient with a tongue cancer?:
      case report.
AB  - BACKGROUND: Von Hippel-Lindau disease (VHL) is a dominantly inherited familial
      cancer syndrome predisposing the patient to a variety of malignant and benign
      neoplasms, most frequently hemangioblastoma, renal cell carcinoma,
      pheochromocytoma, and pancreatic tumors. VHL is caused by mutations of the VHL
      tumor suppressor gene on the short arm of chromosome 3, and clinical
      manifestations develop if both alleles are inactivated according to the two-hit
      hypothesis. VHL mutations are more frequent in the coding region and occur
      occasionally in the splicing region of the gene. Previously, we reported that the
      loss of heterozygosity (LOH) of the VHL gene is common in squamous cell carcinoma
      tissues of the tongue. CASE PRESENTATION: We describe a case of squamous cell
      carcinoma in the tongue caused by a point mutation in the splicing region of the
      VHL gene and discuss its association with VHL disease. Sequence analysis of DNA
      extracted from the tumor and peripheral blood of the patient with squamous cell
      carcinoma revealed a heterozygous germline mutation (c. 340 + 5 G > C) in the
      splice donor sequence in intron 1 of the VHL gene. RT-PCR analysis of the
      exon1/intron1 junction in RNA from tumor tissue detected an unspliced transcript.
      Analysis of LOH using a marker with a heterozygous mutation of nucleotides (G or
      C) revealed a deletion of the mutant C allele in the carcinoma tissues.
      CONCLUSIONS: The fifth nucleotide G of the splice donor site of the VHL gene is
      important for the efficiency of splicing at that site. The development of tongue
      cancer in this patient was not associated with VHL disease because the mutation
      occurred in only a single allele of the VHL gene and that allele was deleted in
      tumor cells.

PMID- 22462638
TI  - Copper(II) triflate catalyzed amination and aziridination of 2-alkyl substituted
      1,3-dicarbonyl compounds.
AB  - A method to prepare alpha-acyl-beta-amino acid and 2,2-diacyl aziridine
      derivatives efficiently from Cu(OTf)(2) + 1,10-phenanthroline (1,10-phen)
      catalyzed amination and aziridination of 2-alkyl substituted 1,3-dicarbonyl
      compounds with PhI?NTs is described. By taking advantage of the orthogonal modes
      of reactivity of the substrate through slight modification of the reaction
      conditions, a divergence in product selectivity was observed. In the presence of
      1.2 equiv of the iminoiodane, amination of the allylic C-H bond of the enolic
      form of the substrate, formed in situ through coordination to the Lewis acidic
      metal catalyst, was found to selectively occur and give the beta-aminated adduct.
      On the other hand, increasing the amount of the nitrogen source from 1.2 to 2-3
      equiv was discovered to result in preferential formal aziridination of the C-C
      bond of the 2-alkyl substituent of the starting material and formation of the
      aziridine product.

PMID- 22462639
TI  - The effect of core material, veneering porcelain, and fabrication technique on
      the biaxial flexural strength and weibull analysis of selected dental ceramics.
AB  - PURPOSE: The objective of this study was to compare the effect of veneering
      porcelain (monolithic or bilayer specimens) and core fabrication technique (heat
      pressed or CAD/CAM) on the biaxial flexural strength and Weibull modulus of
      leucite-reinforced and lithium-disilicate glass ceramics. In addition, the effect
      of veneering technique (heat-pressed or powder/liquid layering) for zirconia
      ceramics on the biaxial flexural strength and Weibull modulus was studied.
      MATERIALS AND METHODS: Five ceramic core materials (IPS Empress Esthetic, IPS
      Empress CAD, IPS e.max Press, IPS e.max CAD, IPS e.max ZirCAD) and three
      corresponding veneering porcelains (IPS Empress Esthetic Veneer, IPS e.max Ceram,
      IPS e.max ZirPress) were selected for this study. Each core material group
      contained three subgroups based on the core material thickness and the presence
      of corresponding veneering porcelain as follows: 1.5 mm core material only
      (subgroup 1.5C), 0.8 mm core material only (subgroup 0.8C), and 1.5 mm
      core/veneer group: 0.8 mm core with 0.7 mm corresponding veneering porcelain with
      a powder/liquid layering technique (subgroup 0.8C-0.7VL). The ZirCAD group had
      one additional 1.5 mm core/veneer subgroup with 0.7 mm heat-pressed veneering
      porcelain (subgroup 0.8C-0.7VP). The biaxial flexural strengths were compared for
      each subgroup (n = 10) according to ISO standard 6872:2008 with ANOVA and Tukey's
      post hoc multiple comparison test (p<= 0.05). The reliability of strength was
      analyzed with the Weibull distribution. RESULTS: For all core materials, the 1.5
      mm core/veneer subgroups (0.8C-0.7VL, 0.8C-0.7VP) had significantly lower mean
      biaxial flexural strengths (p < 0.0001) than the other two subgroups (subgroups
      1.5C and 0.8C). For the ZirCAD group, the 0.8C-0.7VL subgroup had significantly
      lower flexural strength (p= 0.004) than subgroup 0.8C-0.7VP. Nonetheless, both
      veneered ZirCAD groups showed greater flexural strength than the monolithic
      Empress and e.max groups, regardless of core thickness and fabrication
      techniques. Comparing fabrication techniques, Empress Esthetic/CAD, e.max
      Press/CAD had similar biaxial flexural strength (p= 0.28 for Empress pair; p=
      0.87 for e.max pair); however, e.max CAD/Press groups had significantly higher
      flexural strength (p < 0.0001) than Empress Esthetic/CAD groups. Monolithic core
      specimens presented with higher Weibull modulus with all selected core materials.
      For the ZirCAD group, although the bilayer 0.8C-0.7VL subgroup exhibited
      significantly lower flexural strength, it had highest Weibull modulus than the
      0.8C-0.7VP subgroup. CONCLUSIONS: The present study suggests that veneering
      porcelain onto a ceramic core material diminishes the flexural strength and the
      reliability of the bilayer specimens. Leucite-reinforced glass-ceramic cores have
      lower flexural strength than lithium-disilicate ones, while fabrication
      techniques (heat-pressed or CAD/CAM) and specimen thicknesses do not affect the
      flexural strength of all glass ceramics. Compared with the heat-pressed veneering
      technique, the powder/liquid veneering technique exhibited lower flexural
      strength but increased reliability with a higher Weibull modulus for zirconia
      bilayer specimens. Zirconia-veneered ceramics exhibited greater flexural strength
      than monolithic leucite-reinforced and lithium-disilicate ceramics regardless of
      zirconia veneering techniques (heat-pressed or powder/liquid technique).

PMID- 22462640
TI  - Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia.
AB  - OBJECTIVE: Whether vitamin D deficiency in pregnancy is a cause of pre-eclampsia
      remains controversial. Most previous studies to date have assessed exposure at
      only one time-point in pregnancy. We assessed longitudinal vitamin D status
      during pregnancy and the risk of pre-eclampsia. DESIGN: Prospective cohort study.
      SETTING: Seventeen urban obstetric hospitals, Canada. POPULATION: Pregnant women
      who were participants in a trial of vitamin C and E supplementation for the
      prevention of pre-eclampsia. Canadian participants who consented to participate
      in a biobank with plasma specimens available at the baseline visit were included
      (n = 697). METHODS: Maternal plasma 25-hydroxyvitamin D (25(OH)D) concentrations
      were measured at 12-18 and 24-26 weeks of gestation using chemiluminescence
      immunoassay. MAIN OUTCOME MEASURES: Pre-eclampsia. RESULTS: Of the women, 39%
      were vitamin D deficient (25(OH)D <50 nmol/l). A strong positive correlation was
      observed in maternal 25(OH)D concentrations between the two gestational age
      windows (r = 0.69, P < 0.0001). Mean maternal 25(OH)D concentrations at 24-26
      weeks of gestation were significantly lower in women who subsequently developed
      pre-eclampsia compared with those who did not (mean +/- SD: 48.9 +/- 16.8 versus
      57.0 +/- 19.1 nmol/l, P = 0.03). Women with 25(OH)D < 50 nmol/l at 24-26 weeks
      gestation experienced an increased risk of pre-eclampsia (adjusted odds ratio
      3.24, 95% confidence interval 1.37-7.69), whereas the association was not
      statistically significant for maternal 25(OH)D level at 12-18 weeks of gestation.
      CONCLUSIONS: Lower maternal 25(OH)D levels at late mid-trimester were associated
      with an increased risk of pre-eclampsia.

PMID- 22462642
TI  - Essential roles of clinical nurse instructors in Japan: a Delphi study.
AB  - In Japan, the clinical nurse instructor is a staff nurse who teaches in clinical
      practicums. However, there is no consensus on the essential roles that clinical
      nurse instructors are expected to perform. We conducted a three-round Delphi
      survey to clarify the essential roles of the clinical nurse instructor in
      clinical practicums in undergraduate nursing education. The participants were an
      expert panel of 48 professionals in nursing education and clinical practicums,
      who rated the importance of 58 role items that were established through a
      literature review and pilot survey. Thirty one of these items were identified as
      essential roles, based on agreement of 80% or more of respondents. Further
      investigation revealed nine of the 31 items to be core roles, defined as the
      minimum essential roles that must be performed by clinical nurse instructors,
      however busy they become. The nine core roles are related to proper preparation
      for the clinical practicum, patient safety, and coordination with the nursing
      school faculty. It is important for the nursing school faculty to support and
      work in cooperation with clinical nurse instructors to help them fulfill these
      roles.

PMID- 22462641
TI  - Opening of epithelial tight junctions and enhancement of paracellular permeation
      by chitosan: microscopic, ultrastructural, and computed-tomographic observations.
AB  - This study investigates the effects of chitosan (CS) on the opening of epithelial
      tight junctions (TJs) and paracellular transport at microscopic, ultrastructural,
      and computed-tomographic levels in Caco-2 cell monolayers and animal models.
      Using immunofluorescence staining, CS treatment was observed to be associated
      with the translocation of JAM-1 (a trans-membrane TJ protein), resulting in the
      disruption of TJs; the removal of CS was accompanied by the recovery of JAM-1.
      Ultrastructural observations by TEM reveal that CS treatment slightly opened the
      apical intercellular space, allowing lanthanum (an electron-dense tracer) to
      stain the intercellular surface immediately beneath the TJs, suggesting the
      opening of TJs. Following the removal of CS, the TJs were completely recovered.
      Similar microscopic and ultrastructural findings were obtained in animal studies.
      CS nanoparticles were prepared as an insulin carrier. The in vivo fluorescence
      microscopic results demonstrate that insulin could be absorbed into the systemic
      circulation, while most CS was retained in the microvilli scaffolds. These
      observations were verified in a biodistribution study following the oral
      administration of isotope-labeled nanoparticles by single-photon emission
      computed tomography. Above results reveal that CS is a safe permeation enhancer
      and is an effective carrier for oral protein delivery.

PMID- 22462643
TI  - Diagnostics of anodic stripping mechanisms under square-wave voltammetry
      conditions using bismuth film substrates.
AB  - A mechanistic study to provide diagnostics of anodic stripping electrode
      processes at bismuth-film electrodes is presented from both theoretical and
      experimental points of view. Theoretical models for three types of electrode
      mechanisms are developed under conditions of square-wave voltammetry, combining
      rigorous modeling based on integral equations and the step function method,
      resulting in derivation of a single numerical recurrent formula to predict the
      outcome of the voltammetric experiment. In the course of the deposition step, it
      has been assumed that a uniform film of the metal analyte is formed on the
      bismuth substrate, in situ deposited onto a glassy carbon electrode surface,
      without considering mass transfer within either the bismuth or the metal analyte
      film. Theoretical data are analyzed in terms of dimensionless critical parameters
      related with electrode kinetics, mass transfer, adsorption equilibria, and
      possible lateral interactions within the deposited metal particles. Theoretical
      analysis enables definition of simple criteria for differentiation and
      characterization of electrode processes. Comparing theoretical and experimental
      data, anodic stripping processes of zinc(II), cadmium(II), and lead(II) are
      successfully characterized, revealing significant differences in their reaction
      pathways. The proposed easy-to-perform diagnostic route is considered to be of a
      general use while the bismuth film exploited in this study served as a convenient
      nonmercury model substrate surface.

PMID- 22462645
TI  - Recent advances in the pathophysiology and pharmacological treatment of obesity.
AB  - WHAT IS KNOWN AND OBJECTIVE: The increasing prevalence of obesity and associated
      morbidity present unmet medical needs for safe and effective new drug therapies.
      Our aim is to review the diverse targets and compounds that are in clinical
      development. METHODS: Literature searches were conducted using the PUBMED
      database for studies published in English from January 1985 to December 2011
      using combinations of key words, including obesity, overweight, weight loss and
      treatment in addition to the clinical trials website. Bibliographies of selected
      references were also evaluated for relevant articles. Press/news releases were
      also utilized. The collection of information for this review was limited to the
      most recently available human and animal data. RESULTS AND DISCUSSION: Weight
      loss drugs in development include compounds that act centrally (neuropeptide Y,
      AgRP and MCH1 receptors) to limit food intake or reduce the absorption of fat
      from the gastrointestinal tract (lipase inhibitors) or increase energy
      expenditure or reduce adipose tissue formation. Among the existing therapy, new
      combinations (topiramate plus phentermine, bupropion plus naltrexone) offer
      greater efficacy with reduced adverse effects. WHAT IS NEW AND CONCLUSION:
      Despite recent setbacks in the pharmacotherapy of obesity (withdrawal of
      rimonabant and sibutramine), many compounds are in phase II/III trials. The
      future holds promise for a new drug that alone or in combination with an existing
      agent could target the initial pathophysiology and morbidities associated with
      obesity.

PMID- 22462644
TI  - Speeding up chemical searches using the inverted index: the convergence of
      chemoinformatics and text search methods.
AB  - In ligand-based screening, retrosynthesis, and other chemoinformatics
      applications, one often seeks to search large databases of molecules in order to
      retrieve molecules that are similar to a given query. With the expanding size of
      molecular databases, the efficiency and scalability of data structures and
      algorithms for chemical searches are becoming increasingly important. Remarkably,
      both the chemoinformatics and information retrieval communities have converged on
      similar solutions whereby molecules or documents are represented by binary
      vectors, or fingerprints, indexing their substructures such as labeled paths for
      molecules and n-grams for text, with the same Jaccard-Tanimoto similarity
      measure. As a result, similarity search methods from one field can be adapted to
      the other. Here we adapt recent, state-of-the-art, inverted index methods from
      information retrieval to speed up similarity searches in chemoinformatics. Our
      results show a several-fold speed-up improvement over previous methods for both
      threshold searches and top-K searches. We also provide a mathematical analysis
      that allows one to predict the level of pruning achieved by the inverted index
      approach and validate the quality of these predictions through simulation
      experiments. All results can be replicated using data freely downloadable from
      http://cdb.ics.uci.edu/ .

PMID- 22462646
TI  - Prokaryotic expression and immunogenicity of 56-kDa protein of Orientia
      tsutsugamushi strain Karp.
AB  - To express the 56-kDa protein of O. tsutsugamushi strain Karp, this protein gene
      was cloned into pET30a(+) before transforming into host bacteria, E. coli
      Rossetta. Specificity of the recombinant protein was assessed by ELISA using
      rabbit sera against common members of the order Rickettsiae and 10 other
      pathogenic bacteria. After IPTG induction, SDS-PAGE analysis of isolated protein
      demonstrated a band at approximately 46-kDa. Western blot and mass spectrometry
      analysis proved that the recombinant protein was expressed successfully.
      Specificity analysis demonstrated that all sera were negative, except sera
      against O. tsutsugamushi strains TA763, TH1817 and Kato, B. quintana, A.
      phagocytophilum, E. chaffeensis and B. bacilliformis. The purified protein was
      used to immunize BALB/c mice and polyclonal antisera were harvested. By
      examination of IFA and ELISA, the highest titer of the polyclonal antibodies
      reaches 1:1600. The recombinant 56-kDa protein in the study is valuable for
      developing a simple and rapid diagnostic test and vaccine for O. tsutsugamushi.

PMID- 22462647
TI  - Rigid or flexible sigmoidoscopy in colorectal clinics? Appraisal through a
      systematic review and meta-analysis.
AB  - AIM: Rigid sigmoidoscopy is sometimes performed at first presentation in
      colorectal clinics. We assessed the feasibility of flexible sigmoidoscopy in
      similar situations by comparing it with rigid sigmoidoscopy as a first
      investigative tool. METHODS: The Medline, Embase, and Cochrane databases were
      searched for randomized and non-randomized clinical trials comparing the
      usefulness of rigid and flexible sigmoidoscopy. The risk difference (RD) and
      weighted mean difference (WMD) were calculated for the cancers/abnormalities
      detected and discomfort associated with the procedure, respectively. The standard
      mean difference (SMD) was calculated for the depth of examination and duration of
      the procedure. RESULTS: Flexible sigmoidoscopy had a significantly higher rate of
      detection of cancers and total abnormalities (RD of 0.020 and 0.138 and 95%
      confidence interval [CI] of 0.006-0.034 and 0.077-0.200, respectively), and rigid
      sigmoidoscopy caused significantly more patient discomfort (WMD of 0.981 and 95%
      CI of 0.693-1.269). Flexible sigmoidoscopy provided significantly greater depth
      of examination (SMD of 3.175, 95% CI of 2.397-3.954), and rigid sigmoidoscopy
      required less time (SMD of -1.601, 95% CI of -2.728 to -0.474). CONCLUSIONS:
      Flexible sigmoidoscopy is a better investigative tool in colorectal clinics than
      the rigid sigmoidoscopy. Implementation of this idea can help in early diagnosis
      at first presentation and can certainly expedite the management of colorectal
      malignancies.

PMID- 22462648
TI  - Laparoscopic right posterior sectionectomy for hepatocellular carcinoma using a
      modified liver-hanging maneuver.
AB  - BACKGROUND: Posterosuperior liver segments are the most difficult locations for
      laparoscopy to access. This location is considered by most surgeons to be a poor
      indication for a laparoscopic liver resection due to the limited visualization
      and the difficulty of controlling bleeding. The liver-hanging maneuver (LHM) is a
      technique taking aim at reducing intraoperative blood loss through an open
      approach. METHODS: We report our early experience on adopting a modified liver
      hanging technique to perform a totally laparoscopic right posterior sectionectomy
      to remove a 5-cm hepatocellular carcinoma located in Couinaud's segments 6 and 7.
      RESULTS: The procedure was completed laparoscopically with acceptable time of
      surgery and blood loss. A 3.5-cm tumor-free resection margin was achieved. The
      patient was discharged on postoperative Day 10 without complications. No evidence
      of recurrence was seen at the 12-month follow-up. CONCLUSIONS: Total laparoscopic
      posterior sectionectomy using a modified LHM is a possible operative procedure
      greatly facilitating surgical manipulation. This maneuver was successfully used
      to mobilize the liver, to guide the hepatic transection, and to prevent bleeding.
      The potential advantages of this procedure should be evaluated in a comparative
      study on a large number of patients.

PMID- 22462649
TI  - Initial experience of robot-assisted radical cystectomy with total intracorporeal
      urinary diversion: comparison with extracorporeal method.
AB  - PURPOSE: To report our surgical technique and initial experience with robot
      assisted laparoscopic radical cystectomy (RARC) with total intracorporeal urinary
      diversion compared with an extracorporeal method. SUBJECTS AND METHODS: In total,
      42 patients underwent RARC by a single surgeon at our institute for clinically
      localized bladder cancer. Among these, 4 patients underwent RARC with complete
      intracorporeal urinary diversion. An ileal conduit was achieved in 3 patients,
      and an orthotopic neobladder was created in 1 patient. Our surgical technique is
      presented in detail, and the intracorporeal cases were compared with 38 previous
      extracorporeal diversion cases for perioperative outcome, postoperative oncologic
      outcome, and complications. RESULTS: Three men and 1 woman underwent complete
      intracorporeal urinary diversion. In patients receiving ileal conduits the mean
      total operative time was 510 minutes, and the estimated blood loss was 400 mL. In
      the patient receiving an ileal neobladder the total operative time was 585
      minutes, and the estimated blood loss was 500 mL. Mean time to flatus was 60
      hours, and no intraoperative or postoperative major complications occurred.
      Surgical margins were negative with no positive lymph nodes. Compared with
      extracorporeal cases, the mean total operative time for RARC was significantly
      longer, but perioperative outcomes of estimated blood loss, time to flatus, and
      postoperative oncologic outcomes were not significantly different. CONCLUSIONS:
      Our initial experience showed that RARC with complete intracorporeal urinary
      diversion is feasible based on perioperative data and oncologic features.
      However, in this small case series, we observed no definite benefits associated
      with intracorporeal urinary diversion over extracorporeal urinary diversion
      except for better cosmesis. Long-term, large-scale, prospective comparative
      studies will be needed to demonstrate the benefit of intracorporeal urinary
      diversion.

PMID- 22462651
TI  - Organometallic Conformational Equilibria. IX. Isomerism and Hindered Rotation
      about Palladium-Nitrogen Bonds in d-Allyl Complexes.

PMID- 22462650
TI  - Role of comorbidities in outcome prediction after status epilepticus.
AB  - Status epilepticus (SE) is associated with significant mortality and morbidity. A
      reliable prognosis may help better manage medical resources and treatment
      strategies. We examined the role of preexisting comorbidities on the outcome of
      patients with SE, an aspect that has received little attention to date. We
      prospectively studied incident SE episodes in 280 adults occurring over 55 months
      in our tertiary care hospital, excluding patients with postanoxic encephalopathy.
      Different models predicting mortality and return to clinical baseline at hospital
      discharge were compared, which included demographics, SE etiology, a validated
      clinical Status Epilepticus Severity Score (STESS), and comorbidities (assessed
      with the Charlson Comorbidity Index) as independent variables. The overall short
      term mortality was 14%, and only half of patients returned to their clinical
      baseline. On bivariate analyses, age, STESS, potentially fatal etiologies, and
      number of preexisting comorbidities were all significant predictors of both
      mortality and return to clinical baseline. As compared with the simplest
      predictive model (including demographics and deadly etiology), adding SE severity
      and comorbidities resulted in an improved predictive performance (C statistics
      0.84 vs. 0.77 for mortality, and 0.86 vs. 0.82. for return to clinical baseline);
      comorbidities, however, were not independently related to outcome. Considering
      comorbidities and clinical presentation, in addition to age and etiology,
      slightly improves the prediction of SE outcome with respect to both survival and
      functional status. This analysis also emphasizes the robust predictive role of
      etiology and age.

PMID- 22462652
TI  - Deoiledjatropha seed cake is a useful nutrient for pullulan production.
AB  - BACKGROUND: Ever increasing demand for fossil fuels is a major factor for rapid
      depletion of these non-renewable energy resources, which has enhanced the
      interest of finding out alternative sources of energy. In recent years jatropha
      seed oil has been used extensively for production of bio-diesel and has shown
      significant potential to replace petroleum fuels at least partially. De-oiled
      jatropha seed cake (DOJSC) which comprises of approximately 55 to 65% of the
      biomass is a byproduct of bio-diesel industry. DOJSC contains toxic components
      like phorbol esters which restricts its utilization as animal feed. Thus along
      with the enhancement of biodiesel production from jatropha, there is an
      associated problem of handling this toxic byproduct. Utilization of DOJSC as a
      feed stock for production of biochemicals may be an attractive solution to the
      problem.Pullulan is an industrially important polysaccharide with several
      potential applications in food, pharmaceuticals and cosmetic industries. However,
      the major bottleneck for commercial utilization of pullulan is its high cost. A
      cost effective process for pullulan production may be developed using DOJSC as
      sole nutrient source which will in turn also help in utilization of the byproduct
      of bio-diesel industry. RESULTS: In the present study, DOJSC has been used as a
      nutrient for production of pullulan, in place of conventional nutrients like
      yeast extract and peptone. Process optimization was done in shake flasks, and
      under optimized conditions (8% DOJSC, 15% dextrose, 28 degrees C temperature, 200
      rpm, 5% inoculum, 6.0 pH) 83.98 g/L pullulan was obtained. The process was
      further validated in a 5 L laboratory scale fermenter. CONCLUSION: This is the
      first report of using DOJSC as nutrient for production of an exopolysaccharide.
      Successful use of DOJSC as nutrient will help in finding significant application
      of this toxic byproduct of biodiesel industry. This in turn also have a
      significant impact on cost reduction and may lead to development of a cost
      effective green technology for pullulan production.

PMID- 22462653
TI  - Defining 'surveillance' in drug safety.
AB  - The concept of surveillance in pharmacovigilance and pharmacoepidemiology has
      evolved from the concept of surveillance in epidemiology, particularly of
      infectious diseases. We have surveyed the etymology, usages, and previous
      definitions of 'surveillance' and its modifiers, such as 'active' and 'passive'.
      The following essential definitional features of surveillance emerge: (i)
      surveillance and monitoring are different--surveillance involves populations,
      while monitoring involves individuals; (ii) surveillance can be performed
      repeatedly and at any time during the lifetime of a medicinal product or device;
      (iii) although itself non-interventional, it can adduce any types of evidence
      (interventional, observational, or anecdotal, potentially at different times);
      (iv) it encompasses data collection, management, analysis, and interpretation;
      (v) it includes actions to be taken after signal detection, including initial
      evaluation and communication; and (vi) it should contribute to the classification
      of adverse reactions and their prevention or mitigation and/or to the harnessing
      of beneficial effects. We conclude that qualifiers add ambiguity and uncertainty
      without enhancing the idea of surveillance. We propose the following definition
      of surveillance of health-care products, which embraces all the surveyed ideas
      and reflects real-world pharmacovigilance processes: 'a form of non
      interventional public health research, consisting of a set of processes for the
      continued systematic collection, compilation, interrogation, analysis, and
      interpretation of data on benefits and harms (including relevant spontaneous
      reports, electronic medical records, and experimental data).' As a codicil, we
      note that the purposes of surveillance are to identify, evaluate, understand, and
      communicate previously unknown effects of health-care products, or new aspects of
      known effects, in order to harness such effects (if beneficial) or prevent or
      mitigate them (if harmful).

PMID- 22462654
TI  - Prognostic value of Bcl-2 in two independent populations of estrogen receptor
      positive breast cancer patients treated with adjuvant endocrine therapy.
AB  - INTRODUCTION: Estrogen receptor (ER) status is not an optimal marker for response
      to adjuvant endocrine therapy since approximately 30% of patients with ER
      positive tumors eventually relapse. Bcl-2 is regulated by ER and may thus be
      considered as an indicator of ER activity and a candidate supplementary marker to
      ER status. PATIENTS AND METHODS: Tumor tissue from 257 patients with ER-positive
      breast cancer treated with tamoxifen was used for determination of the best
      threshold for immunohistochemical Bcl-2 assessment as prognostic marker.
      Subsequently, samples from the Danish patients of the randomized clinical trial
      BIG 1-98 comprising 1191 ER-positive patients treated with tamoxifen, letrozole
      or a sequence of the two were immunohistochemically stained for Bcl-2 to further
      explore the prognostic value of Bcl-2. RESULTS: Two Bcl-2 levels were found to
      divide the population of the primary study into significantly different groups
      according to disease-free survival (DFS). Multivariate analysis confirmed the
      significance of the lowest level, and showed Bcl-2 to be an independent
      prognostic marker. Analysis of the Danish cohort of the BIG 1-98 confirmed that
      Bcl-2 was a significant predictor of DFS, independent of known prognostic
      markers. However, in an additional analysis of a subset of the Danish cohort of
      BIG 1-98 including only HER-2 normal patients, the effect of Bcl-2 was not
      statistically significant. DISCUSSION: Low Bcl-2 can predict poor outcome of
      patients with ER-positive tumors treated with adjuvant endocrine therapy, whereas
      the use of Bcl-2 for determination of addition of chemotherapy was not supported
      by this study.

PMID- 22462655
TI  - Association between sleep duration and psychological health in overweight and
      obese children in Korea.
AB  - This study examined the moderating effects of different body mass index groups on
      the relationship between sleep duration and psychological variables (i.e. self
      esteem, depression, and perceived obesity stress) among overweight and obese
      children in Korea. A non-experimental, cross-sectional study design was used.
      Study participants included 424 children residing in one metropolitan city of
      Korea and participating in weight-control programs. Self-reported data collection
      and physical examinations were performed. An age- and sex-specific reference
      growth chart was used to produce body mass index for age percentiles, and to
      classify overweight and obese groups. The results indicated that the main effects
      of sleep duration and the body mass index group * sleep duration interaction
      terms were statistically significant for all investigated psychological variables
      (P < 0.05), indicating that the body mass index group variable moderated the
      relationship between sleep duration and these psychological variables. This study
      found that sleep duration < 7 h was particularly detrimental to the investigated
      psychological variables in overweight, rather than obese, children.

PMID- 22462656
TI  - Exercise efficiency of low power output cycling.
AB  - Exercise efficiency at low power outputs, energetically comparable to daily
      living activities, can be influenced by homeostatic perturbations (e.g., weight
      gain/loss). However, an appropriate efficiency calculation for low power outputs
      used in these studies has not been determined. Fifteen active subjects (seven
      females, eight males) performed 14, 5-min cycling trials: two types of seated
      rest (cranks vertical and horizontal), passive (motor-driven) cycling, no-chain
      cycling, no-load cycling, cycling at low (10, 20, 30, 40 W), and moderate (50,
      60, 80, 100, 120 W) power outputs. Mean delta efficiency was 57% for low power
      outputs compared to 41.3% for moderate power outputs. Means for gross (3.6%) and
      net (5.7%) efficiencies were low at the lowest power output. At low power
      outputs, delta and work efficiency values exceeded theoretical values. In
      conclusion, at low power outputs, none of the common exercise efficiency
      calculations gave values comparable to theoretical muscle efficiency. However,
      gross efficiency and the slope and intercept of the metabolic power vs mechanical
      power output regression provide insights that are still valuable when studying
      homeostatic perturbations.

PMID- 22462657
TI  - The development and validation of the Relational Self-Esteem Scale.
AB  - According to the tripartite model of the self (Brewer & Gardner, 1996), the self
      consists of three aspects: personal, relational, and collective. Correspondingly,
      individuals can achieve a sense of self-worth through their personal attributes
      (personal self-esteem), relationship with significant others (relational self
      esteem), or social group membership (collective self-esteem). Existing measures
      on personal and collective self-esteem are available in the literature; however,
      no scale exists that assesses relational self-esteem. The authors developed a
      scale to measure individual differences in relational self-esteem and tested it
      with two samples of Chinese university students. Between and within-network
      approaches to construct validation were used. The scale showed adequate internal
      consistency reliability and results of the confirmatory factor analysis showed
      good fit. It also exhibited meaningful correlations with theoretically relevant
      constructs in the nomological network. Implications and directions for future
      research are discussed.

PMID- 22462658
TI  - Can number and size of offspring increase simultaneously?--a central life-history
      trade-off reconsidered.
AB  - BACKGROUND: To maximize their fitness, parents are assumed to allocate their
      resources optimally between number and size of offspring. Although this
      fundamental life-history trade-off has been subject to long standing interest,
      its genetic basis, especially in wild mammals, still remains unresolved. One
      important reason for this problem is that a large multigenerational pedigree is
      required to conduct a reliable analysis of this trade-off. RESULTS: We used the
      REML-animal model to estimate genetic parameters for litter size and individual
      birth size for a common Palearctic small mammal, the bank vole (Myodes
      glareolus). Even though a phenotypic trade-off between offspring number and size
      was evident, it was not explained by a genetic trade-off, but rather by negative
      correlations in permanent and temporary environmental effects. In fact, even
      positive genetic correlations were estimated between direct genetic effects for
      offspring number and size indicating that genetic variation in these two traits
      is not necessarily antagonistic in mammals. CONCLUSIONS: Our results have notable
      implications for the study of the life-history trade-off between offspring number
      and size in mammals. The estimated genetic correlations suggest that evolution of
      offspring number and size in polytocous mammals is not constrained by the trade
      off caused by antagonistic selection responses per se, but rather by the opposing
      correlative selection responses in direct and maternal genetic effects for birth
      size.

PMID- 22462660
TI  - Standard operating procedures for priapism.
AB  - AIM: To provide standard operating procedures for the diagnosis and management of
      priapism. METHODS: Review of the literature. MAIN OUTCOME MEASURES: Reduction of
      priapism and preservation of erectile function. RESULTS: Priapism is a persistent
      penile erection that continues hours beyond, or is unrelated to, sexual
      stimulation. Priapism requires prompt evaluation and usually requires emergency
      management. There are two types of priapism: (i) ischemic (veno-occlusive or low
      flow), which is found in 95% of cases, and (ii) nonischemic (arterial or high
      flow). Stuttering (intermittent) priapism is a recurrent form of ischemic
      priapism. To initiate appropriate management, the physician must determine
      whether the priapism is ischemic or nonischemic. Necessary diagnostic steps are
      an accurate history, physical examination, and cavernous blood gas analysis
      and/or color duplex ultrasonography of the corpora cavernosa. Management of
      ischemic priapism should achieve resolution as promptly as possible. Initial
      treatment is therapeutic aspiration with or without irrigation of the corpora. If
      this fails, intracavernous injection of sympathomimetic drugs is the next step.
      Surgical shunts should be performed if nonsurgical treatment has failed. The
      initial management of nonischemic priapism should be observation. Selective
      arterial embolization is recommended for the management of nonischemic priapism
      in patients who request treatment. The goal of management for a patient with
      recurrent (stuttering) priapism is prevention of future episodes. CONCLUSION:
      Management of priapism has become increasingly successful as scientific
      understanding of the pathophysiology and molecular biology of priapism improves.
      The key to further success in the treatment of priapism is basic research of this
      uncommon but potentially devastating condition.

PMID- 22462659
TI  - Vascular morphogenesis of adipose-derived stem cells is mediated by heterotypic
      cell-cell interactions.
AB  - Adipose-derived stromal/stem cells (ASCs) are a promising cell source for
      vascular-based approaches to clinical therapeutics, as they have been shown to
      give rise to both endothelial and perivascular cells. While it is well known that
      ASCs can present a heterogeneous phenotypic profile, spontaneous interactions
      among these subpopulations that result in the formation of complex tissue
      structures have not been rigorously demonstrated. Our study reports the novel
      finding that ASCs grown in monolayers in the presence of angiogenic cues are
      capable of self-assembling into complex, three-dimensional vascular structures.
      This phenomenon is only apparent when the ASCs are seeded at a high density
      (20,000 cells/cm(2)) and occur through orchestrated interactions among three
      distinct subpopulations: CD31-positive cells (CD31+), alpha-smooth muscle actin
      positive cells (alphaSMA+), and cells that are unstained for both these markers
      (CD31-/alphaSMA-). Investigations into the kinetics of the process revealed that
      endothelial vessel-like structures initially arose from individual CD31+ cells
      through proliferation and their interactions with CD31-/alphaSMA- cells. During
      this period, alphaSMA+ cells proliferated and appeared to migrate toward the
      vessel structures, eventually engaging in cell-cell contact with them after 1
      week. By 2 weeks, the lumen-containing CD31+ vessels grew greater than a
      millimeter in length, were lined with vascular basement membrane proteins, and
      were encased within a dense, three-dimensional cluster of alphaSMA+ and CD31
      /alphaSMA- cells. The recruitment of alphaSMA+ cells was largely due to platelet
      derived growth factor (PDGF) signaling, as the inhibition of PDGF receptors
      substantially reduced alphaSMA+ cell growth and vessel coverage. Additionally, we
      found that while hypoxia increased endothelial gene expression and vessel width,
      it also inhibited the growth of the alphaSMA+ population. Together, these
      findings underscore the potential use of ASCs in forming mature vessels in vitro
      as well as the need for a further understanding of the heterotypic interactions
      among ASC subpopulations.

PMID- 22462661
TI  - HPV vaccines and autoimmune diseases.

PMID- 22462662
TI  - Intramolecular oxycyanation of alkenes by cooperative Pd/BPh3 catalysis.
AB  - The cooperative catalysis by palladium and triphenylborane effects the
      intramolecular oxycyanation of alkenes through the cleavage of O-CN bonds and the
      subsequent insertion of double bonds. The use of 4,5-bis(diphenylphosphino)-9,9
      dimethylxanthene (Xantphos) as a ligand for palladium is essential for allowing
      the transformation to proceed with high chemo- and regioselectivity. Variously
      substituted dihydrobenzofurans with both a tetra-substituted carbon and cyano
      functionality are accessed by the newly developed methodology.

PMID- 22462663
TI  - The challenges and beauty of peripheral nerve regrowth.
AB  - This review provides an overview of selected aspects of peripheral nerve
      regeneration and potential avenues to explore therapeutically. The overall
      coordinated and orchestrated pattern of recovery from peripheral nerve injury has
      a beauty of execution and progress that rivals all other forms of neurobiology.
      It involves changes at the level of the perikaryon, coordination with important
      peripheral glial partners, the Schwann cells, a controlled inflammatory response,
      and growth that overcomes surprising intrinsic roadblocks. Both regenerative axon
      growth and collateral sprouting encompass fascinating aspects of this story.
      Better understanding of peripheral nerve regeneration may also lead to enhanced
      central nervous system recovery.

PMID- 22462664
TI  - Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and in
      vitro experimental models.
AB  - HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological
      complication of HIV infection and its treatment with some antiretroviral drugs.
      We review the pathogenesis of the viral- and drug-induced causes of the
      neuropathy, and its primary symptom, pain, based on evidence from in vivo and in
      vitro models of HIV-SN. Viral coat proteins mediate nerve fibre damage and
      hypernociception through direct and indirect mechanisms. Direct interactions
      between viral proteins and nerve fibres dominate axonal pathology, while somal
      pathology is dominated by indirect mechanisms that occur secondary to virus
      mediated activation of glia and macrophage infiltration into the dorsal root
      ganglia. The treatment-induced neuropathy and resulting hypernociception arise
      primarily from drug-induced mitochondrial dysfunction, but the sequence of events
      initiated by the mitochondrial dysfunction that leads to the nerve fibre damage
      and dysfunction are still unclear. Overall, the models that have been developed
      to study the pathogenesis of HIV-SN, and hypernociception associated with the
      neuropathy, are reasonable models and have provided useful insights into the
      pathogenesis of HIV-SN. As new models are developed they may ultimately lead to
      identification of therapeutic targets for the prevention or treatment of this
      common neurological complication of HIV infection.

PMID- 22462665
TI  - Demyelinating prenatal and infantile developmental neuropathies.
AB  - The prenatal and infantile neuropathies are an uncommon and complex group of
      conditions, most of which are genetic. Despite advances in diagnostic techniques,
      approximately half of children presenting in infancy remain without a specific
      diagnosis. This review focuses on inherited demyelinating neuropathies presenting
      in the first year of life. We clarify the nomenclature used in these disorders,
      review the clinical features of demyelinating forms of Charcot-Marie-Tooth
      disease with early onset, and discuss the demyelinating infantile neuropathies
      associated with central nervous system involvement. Useful clinical,
      neurophysiologic, and neuropathologic features in the diagnostic work-up of these
      conditions are also presented.

PMID- 22462666
TI  - Behavioral, electrophysiological, and histopathological characterization of a
      severe murine chronic demyelinating polyneuritis model.
AB  - The objective of this study was to define the behavioral, electrophysiological,
      and morphological characteristics of spontaneous autoimmune peripheral
      polyneuropathy (SAPP) in female B7-2 deficient non-obese diabetic (NOD) mice. A
      cohort of 77 female B7-2 deficient and 31 wild-type control NOD mice were studied
      from 18 to 40 weeks of age. At pre-defined time points, the dorsal caudal tail
      and sciatic motor nerve conduction studies (MNCS) were performed. Sciatic nerves
      were harvested for morphological evaluation. SAPP mice showed slowly progressive
      severe weakness in hind and forelimbs without significant recovery after 30 weeks
      of age. MNCS showed progressive reduction in mean compound motor action potential
      amplitudes and conduction velocities, and increase in mean total waveform
      duration from 24 to 27 weeks of age, peaking between 32 and 35 weeks of age.
      Toluidine blue-stained, semi-thin plastic-embedded sections demonstrated focal
      demyelination associated with mononuclear cell infiltration early in the disease
      course, with progressively diffuse demyelination and axonal loss associated with
      more intense mononuclear infiltration at peak severity. Immunohistochemistry
      confirmed macrophage-predominant inflammation. This study verifies SAPP as a
      progressive, unremitting chronic inflammatory demyelinating polyneuropathy with
      axonal loss.

PMID- 22462667
TI  - Nodal proteins are target antigens in Guillain-Barre syndrome.
AB  - Neurofascin-186 (NF186), neuronal cell adhesion molecule (NrCAM), and gliomedin
      are adhesion molecules playing a central role in the formation of nodes of
      Ranvier. In Guillain-Barre syndrome (GBS), immune attack toward the nodes may
      participate in the disabilities. Autoantibodies to NF186 and gliomedin have been
      detected in a rat model of GBS. Here, we investigated the prevalence of
      antibodies against nodal adhesion molecules in patients with GBS or chronic
      inflammatory demyelinating polyneuropathy (CIDP). Sera from 100 GBS patients, 50
      CIDP patients, 80 disease controls, and 50 healthy controls were tested for their
      ability to bind the nodes of Ranvier. To characterize the antigens, we performed
      cell binding assays against NF186, gliomedin, contactin, and NrCAM. We found that
      43% of patients with GBS and 30% of patients with CIDP showed IgG fixation at
      nodes or paranodes. In eight patients with GBS or CIDP, we identified that IgG
      antibodies recognized the native extracellular domain of NF186, gliomedin, or
      contactin. Also, 29 patients showed IgM against nodal adhesion molecules.
      However, we did not detect IgM fixation at nodes or paranodes. Antibodies to
      gliomedin or NF186 were mostly detected in demyelinating and axonal GBS,
      respectively. The adsorption of the antibodies to their soluble antigens
      abolished IgG deposition at nodes and paranodes in nerves, indicating these were
      specific to NF186, gliomedin, and contactin. In conclusion, gliomedin, NF186, and
      contactin are novel target antigens in GBS. At nodes, additional epitopes are
      also the targets of IgG. These results suggest that antibody attack against nodal
      antigens participates in the etiology of GBS.

PMID- 22462668
TI  - Single-nucleotide polymorphism of transient axonal glycoprotein-1 and its
      correlation with clinical features and prognosis in chronic inflammatory
      demyelinating polyneuropathy.
AB  - The single-nucleotide polymorphism (SNP) rs2275697 in the transient axonal
      glycoprotein-1 (TAG-1) gene was reported to be associated with responsiveness to
      intravenous immunoglobulin (IVIG) treatment in patients with chronic inflammatory
      demyelinating polyneuropathy (CIDP). However, it is not known if this SNP is
      associated with long-term prognosis. We examined the case records of 32 Chinese
      CIDP patients. The overall response rate to IVIG, prednisolone, or plasmapheresis
      was 83%. After 5.4 years, 57% of patients were on maintenance immunotherapy.
      Patients with higher modified Rankin score and more prolonged distal motor
      latencies in the upper limbs on presentation had a higher risk (odds ratio [OR]
      3.86, 95% confidence interval [CI] 1.23-12.11 and OR 1.04, 95% CI 1.01-1.07,
      respectively) of being on maintenance immunotherapy. Blood samples from 24
      patients and 147 controls were examined for their genotypes of four non
      synonymous SNPs (rs41264871, rs36074532, rs5611135, and rs2275697) in the coding
      region of TAG-1. The G allelic frequency of rs2275697 was similar between CIDP
      patients and controls (56% and 50%, respectively) and was not associated with
      treatment responsiveness, treatment dependence, disability, or mortality.

PMID- 22462669
TI  - Vincristine and bortezomib cause axon outgrowth and behavioral defects in larval
      zebrafish.
AB  - Peripheral neuropathy is a common side effect of a number of pharmaceutical
      compounds, including several chemotherapy drugs. Among these are vincristine
      sulfate, a mitotic inhibitor used to treat a variety of leukemias, lymphomas, and
      other cancers, and bortezomib, a 26S proteasome inhibitor used primarily to treat
      relapsed multiple myeloma and mantle cell lymphoma. To gain insight into the
      mechanisms by which these compounds act, we tested their effects in zebrafish.
      Vincristine or bortezomib given during late embryonic development caused
      significant defects at both behavioral and cellular levels. Intriguingly, the
      effects of the two drugs appear to be distinct. Vincristine causes uncoordinated
      swimming behavior, which is coupled with a reduction in the density of sensory
      innervation and overall size of motor axon arbors. Bortezomib, in contrast,
      increases the duration and amplitude of muscle contractions associated with
      escape swimming, which is coupled with a preferential reduction in fine processes
      and branches of sensory and motor axons. These results demonstrate that zebrafish
      is a convenient in vivo assay system for screening potential pharmaceutical
      compounds for neurotoxic side effects, and they provide an important step toward
      understanding how vincristine and bortezomib cause peripheral neuropathy.

PMID- 22462670
TI  - Heterogeneous spectrum of neuropathies in Waldenstrom's macroglobulinemia: a
      diagnostic strategy to optimize their management.
AB  - Neuropathy in Waldenstrom's macroglobulinemia (WM) is very heterogeneous. We
      retrospectively studied 40 patients with WM and neuropathy to analyze the
      different presentations and mechanisms encountered and to propose a diagnostic
      strategy. Twenty-five patients (62.5%) had axonal neuropathy, related to the
      following mechanisms: amyloid neuropathy (n = 5), cryoglobulinemic neuropathy (n
      = 5), neuropathy associated with tumoral infiltration (n = 2), vasculitic
      neuropathy (n = 2), a clinical motor neuropathy possibly of dysimmune origin (n =
      6), or an unclassified mechanism (n = 5). A demyelinating pattern was observed in
      15 patients, 10 having anti-myelin-associated glycoprotein (anti-MAG) antibodies
      and 5 having neuropathy related to chronic inflammatory demyelinating
      polyradiculoneuropathy. On the basis of these results, we propose a diagnostic
      strategy combining: (1) an EMG to distinguish between a demyelinating and an
      axonal pattern; (2) measurement of anti-MAG and anti-ganglioside antibodies; (3)
      screening for "red flag" features to orientate further investigations. This
      strategy may help clinicians to identify the mechanism of neuropathy in order to
      adapt the therapeutic strategy.

PMID- 22462671
TI  - Protons regulate the excitability properties of rat myelinated sensory axons in
      vitro through block of persistent sodium currents.
AB  - Little information is available on the pH sensitivity of the excitability
      properties of mammalian axons. Computer-assisted threshold tracking in humans has
      helped to define clinically relevant changes of nerve excitability in response to
      hyperventilation and ischaemia, but in vivo studies cannot directly differentiate
      between the impact of pH and other secondary factors. In this investigation, we
      applied an excitability testing protocol to a rat saphenous skin nerve in vitro
      preparation. Changes in extracellular pH were induced by altering pCO(2)  in the
      perfusate, and excitability properties of large myelinated fibres were measured
      in the pH range from 6.9 to 8.1. The main effect of protons on nerve excitability
      was a near linear increase in threshold which was accompanied by a decrease in
      strength-duration time constant reflecting mainly a decrease in persistent sodium
      current. In the recovery cycle, late subexcitability following 7 conditioning
      stimuli was substantially reduced at acid pH, indicating a block of slow but not
      of fast potassium channels. Changes in threshold electrotonus were complex,
      reflecting the combined effects of pH on multiple channel types. These results
      provide the first systematic data on pH sensitivity of mammalian nerve
      excitability properties, and may help in the interpretation of abnormal clinical
      excitability measurements.

PMID- 22462672
TI  - Characteristics of clinical and electrophysiological pattern of Charcot-Marie
      Tooth 4C.
AB  - To describe the clinical and electrophysiological features evoking CMT4C, an
      autosomal recessive (AR) form of Charcot-Marie-Tooth disease (CMT) due to
      mutations in the SH3TC2 gene, we screened the coding sequence of SH3TC2 gene in
      102 unrelated patients with a demyelinating or intermediate CMT and a family
      history compatible with an AR transmission. We identified among this cohort 16
      patients carrying two mutations in the SH3TC2 gene, but medical records finally
      analyzed 14 patients. We report clinical, electrophysiological, and molecular
      data of 14 patients (9 men, 5 women) with CMT4C. Mean age at examination was 43.6
      years (median = 42.5). Among the 14 studied cases 6 had scoliosis as the
      presenting sign. Cranial nerve involvement affecting either the VIIIth, VIIth,
      XIIth or a combination of the IXth and Xth nerves was noted in 10 patients.
      Remarkably, 50% of the patients had proximal limb involvement at the time of
      examination. The hallmark of the electrophysiological study was the presence of
      probable conduction block and temporal dispersion. Thus the clinical and
      paraclinical spectrum of CMT4C can guide the clinician to perform analysis of the
      SH3TC2 gene.

PMID- 22462674
TI  - Presence of repeater F-waves in the early stage of Guillain-Barre syndrome.
AB  - The absence or a prolonged latency of late responses, like F-waves, is a common
      neurophysiological finding with diagnostic utility in the early Guillain-Barre
      syndrome. However, the presence and the number of repeater F-waves have not been
      studied in this disease. In four patients, we report the transient presence of
      repeater F-waves in nerves of the lower limbs shortly after the onset of the
      disease. In each patient, the initial (diagnostic) nerve conduction study showed
      a high incidence of repeater F-waves in the tibial or in the peroneal nerves of
      one side, with normal distal motor latencies; in the other nerves explored the F
      waves were fully abolished and the motor potentials were abnormal. In a second
      study, done 2-6 weeks later, we observed the abolition of the F-waves or a
      significant increase of its minimal latency in those nerves in which we had
      detected the repeaters. The presence of a high number of repeater F-waves with
      normal latencies in some nerves may be a transient and initial
      electrophysiological sign useful in the early diagnosis of this disease.

PMID- 22462673
TI  - Expanding the differential diagnosis of inherited neuropathies with non-uniform
      conduction: Andermann syndrome.
AB  - Uniform conduction slowing has been considered a characteristic of inherited
      demyelinating neuropathies. We present an 18-year-old girl, born from first
      cousins, that presented a late motor and psychological development, cerebellar
      ataxia, facial diplegia, abnormal eye movement, scoliosis, and corpus callosum
      agenesis, whose compound muscle action potentials were slowed and dispersed. A
      mutation was found on KCC3 gene, confirming Andermann syndrome, a disease that
      must be included in the differential diagnosis of inherited neuropathies with non
      uniform conduction slowing.

PMID- 22462675
TI  - Infantile onset CMT2D/dSMA V in monozygotic twins due to a mutation in the
      anticodon-binding domain of GARS.
AB  - Mutations in the GARS gene cause Charcot-Marie-Tooth 2D and distal spinal
      muscular atrophy type V - allelic disorders characterized by predominantly distal
      upper extremity weakness and atrophy, typically beginning during the second
      decade of life. We report monozygotic twin girls with onset of weakness in
      infancy and a previously reported GARS mutation within the anticodon-binding
      domain. The severity and remarkable similarity in phenotypes of these girls and
      the reported case suggest that mutations within the anticodon-binding domain are
      more damaging to aminoacyl tRNA synthetase function than those within other
      domains of GARS.

PMID- 22462676
TI  - Recurrent GBS with GD1a anti-ganglioside antibodies.

PMID- 22462677
TI  - Familial amyloid polyneuropathy associated with nodular lumbosacral
      radiculoplexopathy.

PMID- 22462679
TI  - Regulated expression of pH sensing G Protein-coupled receptor-68 identified
      through chemical biology defines a new drug target for ischemic heart disease.
AB  - Chemical biology promises discovery of new and unexpected mechanistic pathways,
      protein functions and disease targets. Here, we probed the mechanism-of-action
      and protein targets of 3,5-disubstituted isoxazoles (Isx), cardiomyogenic small
      molecules that target Notch-activated epicardium-derived cells (NECs) in vivo and
      promote functional recovery after myocardial infarction (MI). Mechanistic studies
      in NECs led to an Isx-activated G(q) protein-coupled receptor (G(q)PCR)
      hypothesis tested in a cell-based functional target screen for GPCRs regulated by
      Isx. This screen identified one agonist hit, the extracellular proton/pH-sensing
      GPCR GPR68, confirmed through genetic gain- and loss-of-function. Overlooked
      until now, GPR68 expression and localization were highly regulated in early post
      natal and adult post-infarct mouse heart, where GPR68-expressing cells
      accumulated subepicardially. Remarkably, GPR68-expressing cardiomyocytes
      established a proton-sensing cellular "buffer zone" surrounding the MI. Isx
      pharmacologically regulated gene expression (mRNAs and miRs) in this GPR68
      enriched border zone, driving cardiomyogenic and pro-survival transcriptional
      programs in vivo. In conclusion, we tracked a (micromolar) bioactive small
      molecule's mechanism-of-action to a candidate target protein, GPR68, and
      validated this target as a previously unrecognized regulator of myocardial
      cellular responses to tissue acidosis, setting the stage for future (nanomolar)
      target-based drug lead discovery.

PMID- 22462680
TI  - The health impact of mandatory bicycle helmet laws.
AB  - This article seeks to answer the question whether mandatory bicycle helmet laws
      deliver a net societal health benefit. The question is addressed using a simple
      model. The model recognizes a single health benefit--reduced head injuries--and a
      single health cost-increased morbidity due to foregone exercise from reduced
      cycling. Using estimates suggested in the literature on the effectiveness of
      helmets, the health benefits of cycling, head injury rates, and reductions in
      cycling leads to the following conclusions. In jurisdictions where cycling is
      safe, a helmet law is likely to have a large unintended negative health impact.
      In jurisdictions where cycling is relatively unsafe, helmets will do little to
      make it safer and a helmet law, under relatively extreme assumptions, may make a
      small positive contribution to net societal health. The model serves to focus the
      mandatory bicycle helmet law debate on overall health.

PMID- 22462681
TI  - Predicting hand function after hemispherotomy: TMS versus fMRI in hemispheric
      polymicrogyria.
AB  - Patients with hemispheric malformations of cortical development (such as
      polymicrogyria) often develop medically intractable epilepsies for which
      hemispherotomy can be an excellent treatment option. Transcranial magnetic
      stimulation (TMS) and functional magnetic resonance imaging (fMRI) are
      noninvasive methods used to evaluate the sensorimotor system in adults and
      children before surgery. Preoperative results of both methods and their
      predictive values regarding hand function after hemispherotomy are described in
      four boys with hemispheric polymicrogyria, pharmacoresistent epilepsy, and
      hemiparesis with preserved grasp function of the paretic hand. TMS showing
      ipsilateral projections from the contralesional hemisphere but no evidence of
      crossed corticospinal projections from the lesioned hemisphere correctly
      predicted preserved postoperative grasp function in all four patients. In
      contrast, the interpretation of sensorimotor fMRI in patients with congenital
      hemiparesis is more difficult, as ipsilesional activation can occur as it was the
      case in three of four patients in the current study. This activation might
      represent contralaterally preserved primary somatosensory (S1) and not primary
      motor (M1) representation and is apparently not necessary for the paretic hand to
      still perform grasp movements.

PMID- 22462682
TI  - Increased platelet activation in cirrhosis via oxidative stress.

PMID- 22462683
TI  - Enhancement of the proline and nitric oxide synthetic pathway improves
      fermentation ability under multiple baking-associated stress conditions in
      industrial baker's yeast.
AB  - BACKGROUND: During the bread-making process, industrial baker's yeast, mostly
      Saccharomyces cerevisiae, is exposed to baking-associated stresses, such as air
      drying and freeze-thaw stress. These baking-associated stresses exert severe
      injury to yeast cells, mainly due to the generation of reactive oxygen species
      (ROS), leading to cell death and reduced fermentation ability. Thus, there is a
      great need for a baker's yeast strain with higher tolerance to baking-associated
      stresses. Recently, we revealed a novel antioxidative mechanism in a laboratory
      yeast strain that is involved in stress-induced nitric oxide (NO) synthesis from
      proline via proline oxidase Put1 and N-acetyltransferase Mpr1. We also found that
      expression of the proline-feedback inhibition-less sensitive mutant gamma
      glutamyl kinase (Pro1-I150T) and the thermostable mutant Mpr1-F65L resulted in an
      enhanced fermentation ability of baker's yeast in bread dough after freeze-thaw
      stress and air-drying stress, respectively. However, baker's yeast strains with
      high fermentation ability under multiple baking-associated stresses have not yet
      been developed. RESULTS: We constructed a self-cloned diploid baker's yeast
      strain with enhanced proline and NO synthesis by expressing Pro1-I150T and Mpr1
      F65L in the presence of functional Put1. The engineered strain increased the
      intracellular NO level in response to air-drying stress, and the strain was
      tolerant not only to oxidative stress but also to both air-drying and freeze-thaw
      stresses probably due to the reduced intracellular ROS level. We also showed that
      the resultant strain retained higher leavening activity in bread dough after air
      drying and freeze-thaw stress than that of the wild-type strain. On the other
      hand, enhanced stress tolerance and fermentation ability did not occur in the
      put1-deficient strain. This result suggests that NO is synthesized in baker's
      yeast from proline in response to oxidative stresses that induce ROS generation
      and that increased NO plays an important role in baking-associated stress
      tolerance. CONCLUSIONS: In this work, we clarified the importance of Put1- and
      Mpr1-mediated NO generation from proline to the baking-associated stress
      tolerance in industrial baker's yeast. We also demonstrated that baker's yeast
      that enhances the proline and NO synthetic pathway by expressing the Pro1-I150T
      and Mpr1-F65L variants showed improved fermentation ability under multiple baking
      associated stress conditions. From a biotechnological perspective, the
      enhancement of proline and NO synthesis could be promising for breeding novel
      baker's yeast strains.

PMID- 22462684
TI  - Health care professionals' perspectives on oral care for long-term care
      residents: nursing staff, speech-language pathologists and dental hygienists.
AB  - BACKGROUND: Oral health has been identified as a key factor in general health and
      systemic disease in long-term care populations. To optimise oral health of this
      population, it is important to understand the oral care perspectives held by
      health care professionals involved in oral care provision. OBJECTIVES: To explore
      perspectives regarding oral care held by nursing staff, speech-language
      pathologists (SLPs) and dental hygienists (DHs) in long-term care institutions
      and to understand how their perspectives impact activities and processes involved
      in the delivery of oral care. METHODS: A focus group methodology was utilised.
      Separate focus groups for each targeted profession were held. Transcribed data
      were analysed using constant comparative analysis. RESULTS: Daily oral health
      maintenance and monitoring was considered a role of nursing staff. SLPs and DHs
      have roles focusing on advocacy, education and supplemental care. Social factors
      motivate nursing staff to provide oral care, whereas factors related to the
      general health consequences of poor oral health underlined the motivations of
      SLPs and DHs. CONCLUSIONS: Education and training initiatives incorporating
      social aspects of oral health may be more effective for motivating nursing staff
      than approaches emphasising physical risk factors. Organisations can foster
      environments that support collaboration and communication amongst the members of
      multidisciplinary teams in order to promote oral health as a priority.

PMID- 22462686
TI  - Understanding histone deacetylases in the cancer development and treatment: an
      epigenetic perspective of cancer chemotherapy.
AB  - Cancer is a pathologic condition that involves genetic and epigenetic events
      culminating in neoplastic transformation. Alteration in epigenetic events that
      regulate the transcriptional activity of genes associated with various signaling
      pathways can influence multiple stages of tumorigenesis. In cancer cells, an
      imbalance often exists between histone acetyl transferase and histone deacetylase
      (HDAC) activities, and current research focuses actively on seeking competitive
      HDAC inhibitors (HDACi) for chemotherapeutic intervention. HDACi are proving
      useful for cancer prevention and therapy by virtue of their ability to reactivate
      the expression of epigenetically silenced genes, including those involved in
      differentiation, cell cycle regulation, apoptosis, angiogenesis, invasion, and
      metastasis. Furthermore, epidemiological studies suggest that different diets
      such as intake of cruciferous vegetables may lower the risk of different cancers,
      and there is growing interest in identifying the specific chemoprotective
      constituents and mechanistic insights of their action. Interestingly, it has been
      observed that cancer cells are more sensitive than nontransformed cells to
      apoptotic induction by some HDACi. Although the mechanistic basis for this
      sensitivity is unclear, yet HDACi have emerged as important epigenetic target for
      single and combinatorial chemotherapy. HDACi derived from diverse sources such as
      microbial, dietary, and synthetic increase acetylation level of cells and bring
      about anti-proliferative and apoptotic effects specific to cancer cells by way of
      their role in cell cycle regulation and expression of epigenetically silenced
      genes.

PMID- 22462687
TI  - Magnetic Studies on Amino Acid Complexes of Copper (II). II. Novel Interactions
      in Tetrakis(L-tyrosinato)dicopper(II).

PMID- 22462685
TI  - An optimally evolved connective ratio of neural networks that maximizes the
      occurrence of synchronized bursting behavior.
AB  - BACKGROUND: Synchronized bursting activity (SBA) is a remarkable dynamical
      behavior in both ex vivo and in vivo neural networks. Investigations of the
      underlying structural characteristics associated with SBA are crucial to
      understanding the system-level regulatory mechanism of neural network behaviors.
      RESULTS: In this study, artificial pulsed neural networks were established using
      spike response models to capture fundamental dynamics of large scale ex vivo
      cortical networks. Network simulations with synaptic parameter perturbations
      showed the following two findings. (i) In a network with an excitatory ratio (ER)
      of 80-90%, its connective ratio (CR) was within a range of 10-30% when the
      occurrence of SBA reached the highest expectation. This result was consistent
      with the experimental observation in ex vivo neuronal networks, which were
      reported to possess a matured inhibitory synaptic ratio of 10-20% and a CR of 10
      30%. (ii) No SBA occurred when a network does not contain any all-positive
      interaction feedback loop (APFL) motif. In a neural network containing APFLs, the
      number of APFLs presented an optimal range corresponding to the maximal
      occurrence of SBA, which was very similar to the optimal CR. CONCLUSIONS: In a
      neural network, the evolutionarily selected CR (10-30%) optimizes the occurrence
      of SBA, and APFL serves a pivotal network motif required to maximize the
      occurrence of SBA.

PMID- 22462688
TI  - Comparison of sample preparation methods for stable isotope analysis of dissolved
      sulphate in forested watersheds.
AB  - Pretreatment methods for measuring stable sulphur (delta(34)S) and oxygen
      (delta(18)O) isotope ratios of dissolved sulphate from watersheds have evolved
      throughout the last few decades. The current study evaluated if there are
      differences in the measured stable S and O isotope values of dissolved sulphate
      from forested watersheds when pretreated using three different methods: Method 1
      (M1): adsorb sulphate on anion exchange resins and send directly to isotope
      facility; Method 2 (M2): adsorb sulphate on anion exchange resins, extract
      sulphate from anion exchange resins, and send the produced BaSO(4) to the isotope
      facility; and Method 3 (M3): directly precipitate BaSO(4) without anion exchange
      resins with the precipitates being sent to the isotope facility. We found an
      excellent agreement of the delta(34)S(sulphate) values among all the three
      methods. However, some differences were observed in the delta(18)O(sulphate)
      values (M1 versus M2:-1.5 0/00; M1 versus M3:-1.2 0/00) associated with possible
      O contamination before isotope measurement. Several approaches are recommended to
      improve the pretreatment procedures for delta(18)O(sulphate) analysis.

PMID- 22462689
TI  - Structure of charged cyclohexyldiamines in aqueous solution: a theoretical and
      experimental study.
AB  - The structure of mono- and diprotonated cyclohexyldiamine isomers in aqueous
      solution is investigated theoretically by the application of the CPCM continuum
      solvation model combined with the MP2/aug-cc-pVDZ model chemistry. The calculated
      Gibbs energy of hydration (DeltaGhyd) is expressed in different terms with
      physical meaning: cavity formation, solute conformational variation, and solute
      solvent interaction. Significant differences of the DeltaGhyd values are found
      among isomers, which are interpreted based on the analysis of the factors
      accounting for the stability of the conformers/isomers in the gas and solution
      phases. Particular attention is given to the role played by the formation of an
      intramolecular hydrogen bond in the monoprotonated forms and by the Coulombic
      repulsion between the NH3(+) groups in the diprotonated ones. From the Gibbs
      energies of the acid/base pairs in the gas phase and respective hydration Gibbs
      energies, the acidity constants (pKa) are calculated and interpreted. For some
      isomers, the constants are also determined experimentally by potentiometric
      titration. A good agreement was found between the calculated and experimental
      values. 

PMID- 22462690
TI  - Advances in biophysical and bioanalytical protein characterization.

PMID- 22462691
TI  - The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4
      and inhibits the PI3K and Ras signaling pathways.
AB  - AIMS: The metastasis suppressor gene, N-myc downstream regulated gene-1 (NDRG1),
      is negatively correlated with tumor progression in multiple neoplasms, including
      pancreatic cancer. Moreover, NDRG1 is an iron-regulated gene that is markedly
      upregulated by cellular iron-depletion using novel antitumor agents such as the
      chelator, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), in
      pancreatic cancer cells. However, the exact function(s) of NDRG1 remain to be
      established and are important to elucidate. RESULTS: In the current study, using
      gene-array analysis along with NDRG1 overexpression and silencing, we identified
      the molecular targets of NDRG1 in three pancreatic cancer cell lines. We
      demonstrate that NDRG1 upregulates neural precursor cell expressed
      developmentally downregulated 4-like (NEDD4L) and GLI-similar-3 (GLIS3). Further
      studies examining the downstream effects of NEDD4L led to the discovery that
      NDRG1 affects the transforming growth factor-beta (TGF-beta) pathway, leading to
      the upregulation of two key tumor suppressor proteins, namely phosphatase and
      tensin homolog deleted on chromosome 10 (PTEN) and mothers against
      decapentaplegic homolog-4 (SMAD4). Moreover, NDRG1 inhibited the
      phosphatidylinositol 3-kinase (PI3K) and Ras oncogenic pathways. INNOVATION: This
      study provides significant insights into the mechanisms underlying the antitumor
      activity of NDRG1. For the first time, a role for NDRG1 is established in
      regulating the key signaling pathways involved in oncogenesis (TGF-beta, PI3K,
      and Ras pathways). CONCLUSION: The identified target genes of NDRG1 and their
      effect on the TGF-beta signaling pathway reveal its molecular function in
      pancreatic cancer and a novel therapeutic avenue.

PMID- 22462692
TI  - How to improve walking, balance and social participation following stroke: a
      comparison of the long term effects of two walking aids--canes and an orthosis
      TheraTogs--on the recovery of gait following acute stroke. A study protocol for a
      multi-centre, single blind, randomised control trial.
AB  - BACKGROUND: Annually, some 9000 people in Switzerland suffer a first time stroke.
      Of these 60% are left with moderate to severe walking disability. Evidence shows
      that rehabilitation techniques which emphasise activity of the hemiplegic side
      increase ipsilesional cortical plasticity and improve functional outcomes. Canes
      are commonly used in gait rehabilitation although they significantly reduce
      hemiplegic muscle activity. We have shown that an orthosis "TheraTogs" (a corset
      with elasticated strapping) significantly increases hemiplegic muscle activity
      during gait. The aim of the present study is to investigate the long term effects
      on the recovery of gait, balance and social participation of gait rehabilitation
      with TheraTogs compared to gait rehabilitation with a cane following first time
      acute stroke. METHODS/DESIGN: Multi-centre, single blind, randomised trial with
      120 patients after first stroke. When subjects have reached Functional Ambulation
      Category 3 they will be randomly allocated into TheraTogs or cane group.
      TheraTogs will be applied to support hip extensor and abductor musculature
      according to a standardised procedure. Cane walking held at the level of the
      radial styloid of the sound wrist. Subjects will walk throughout the day with
      only the assigned walking aid. Standard therapy treatments and usual care will
      remain unchanged and documented. The intervention will continue for five weeks or
      until patients have reached Functional Ambulation category 5. Outcome measures
      will be assessed the day before begin of intervention, the day after completion,
      3 months, 6 months and 2 years. PRIMARY OUTCOME: Timed "up and go" test,
      secondary outcomes: peak surface EMG of gluteus maximus and gluteus medius,
      activation patterns of hemiplegic leg musculature, temporo-spatial gait
      parameters, hemiplegic hip kinematics in the frontal and sagittal planes, dynamic
      balance, daily activity measured by accelerometry, Stroke Impact Scale.
      Significance levels will be 5% with 95% CI's. IntentionToTreat analyses will be
      performed. Descriptive statistics will be presented. DISCUSSION: This study could
      have significant implications for the clinical practice of gait rehabilitation
      after stroke, particularly the effect and appropriate use of walking aids.The
      results could be important for the development of clinical guidelines and for the
      socio-economic costs of post-stroke care. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov NCT01366729.

PMID- 22462693
TI  - Highly sensitive magnetite nano clusters for MR cell imaging.
AB  - High sensitivity and suitable sizes are essential for magnetic iron oxide
      contrast agents for cell imaging. In this study, we have fabricated highly MR
      sensitive magnetite nanoclusters (MNCs) with tunable sizes. These clusters
      demonstrate high MR sensitivity. Especially, water suspensions of the MNCs with
      average size of 63 nm have transverse relaxivity as high as 630 s-1mM-1, which is
      among the most sensitive iron oxide contrast agents ever reported. Importantly,
      such MNCs have no adverse effects on cells (RAW 264.7). When used for cell
      imaging, they demonstrate much higher efficiency and sensitivity than those of
      SHU555A (Resovist), a commercially available contrast agent, both in vitro and in
      vivo, with detection limits of 3,000 and 10,000 labeled cells, respectively. The
      studied MNCs are sensitive for cell imaging and promising for MR cell tracking in
      clinics.

PMID- 22462695
TI  - Issues in the economic evaluation of influenza vaccination by injection of
      healthy working adults in the US: a review and decision analysis of ten published
      studies.
AB  - The objective was to review recent economic evaluations of influenza vaccination
      by injection in the US, assess their evidence, and conclude on their collective
      findings. The literature was searched for economic evaluations of influenza
      vaccination injection in healthy working adults in the US published since 1995.
      Ten evaluations described in nine papers were identified. These were synopsized
      and their results evaluated, the basic structure of all evaluations was
      ascertained, and sensitivity of outcomes to changes in parameter values were
      explored using a decision model. Areas to improve economic evaluations were
      noted. Eight of nine evaluations with credible economic outcomes were favourable
      to vaccination, representing a statistically significant result compared with a
      proportion of 50% that would be expected if vaccination and no vaccination were
      economically equivalent. Evaluations shared a basic structure, but differed
      considerably with respect to cost components, assumptions, methods, and parameter
      estimates. Sensitivity analysis indicated that changes in parameter values within
      the feasible range, individually or simultaneously, could reverse economic
      outcomes. Given stated misgivings, the methods of estimating influenza reduction
      ascribed to vaccination must be researched to confirm that they produce accurate
      and reliable estimates. Research is also needed to improve estimates of the costs
      per case of influenza illness and the costs of vaccination. Based on their
      assumptions, the reviewed papers collectively appear to support the economic
      benefits of influenza vaccination of healthy adults. Yet the underlying
      assumptions, methods and parameter estimates themselves warrant further research
      to confirm they are accurate, reliable and appropriate to economic evaluation
      purposes.

PMID- 22462694
TI  - A critical review of model-based economic studies of depression: modelling
      techniques, model structure and data sources.
AB  - Depression is the most common mental health disorder and is recognized as a
      chronic disease characterized by multiple acute episodes/relapses. Although
      modelling techniques play an increasingly important role in the economic
      evaluation of depression interventions, comparatively little attention has been
      paid to issues around modelling studies with a focus on potential biases. This,
      however, is important as different modelling approaches, variations in model
      structure and input parameters may produce different results, and hence different
      policy decisions. This paper presents a critical review of literature on recently
      published model-based cost-utility studies of depression. Taking depression as an
      illustrative example, through this review, we discuss a number of specific issues
      in relation to the use of decision-analytic models including the type of
      modelling techniques, structure of models and data sources. The potential
      benefits and limitations of each modelling technique are discussed and factors
      influencing the choice of modelling techniques are addressed. This review found
      that model-based studies of depression used various simulation techniques. We
      note that a discrete-event simulation may be the preferred technique for the
      economic evaluation of depression due to the greater flexibility with respect to
      handling time compared with other individual-based modelling techniques.
      Considering prognosis and management of depression, the structure of the reviewed
      models are discussed. We argue that a few reviewed models did not include some
      important structural aspects such as the possibility of relapse or the increased
      risk of suicide in patients with depression. Finally, the appropriateness of data
      sources used to estimate input parameters with a focus on transition
      probabilities is addressed. We argue that the above issues can potentially bias
      results and reduce the comparability of economic evaluations.

PMID- 22462696
TI  - Editorial: pediatric moyamoya.

PMID- 22462697
TI  - Spontaneous occlusion of the circle of Willis in children: pediatric moyamoya
      summary with proposed evidence-based practice guidelines. A review.
AB  - Moyamoya is a progressive arteriopathy of unknown origin affecting the branches
      of the internal carotid artery (ICA). The arteriopathy can present as an isolated
      medical condition, affecting both sides of the brain ("moyamoya disease") or can
      be unilateral or found in association with systemic disorders ("moyamoya
      syndrome"). The ischemia resulting from luminal narrowing predisposes children to
      transient ischemic attacks and stroke-the primary presentations of affected
      patients. Although it is rare-affecting 1 in 1 million children in the US
      moyamoya is implicated in 6% of all childhood strokes. Diagnosis is defined by
      characteristic findings on arteriograms, including stenosis of the branches of
      the ICA and a pathognomonic spray of small collateral vessels in this region,
      descriptively likened to a "puff of smoke" ("moyamoya" in Japanese). Treatment is
      predicated on restoration of cerebral blood flow by surgical revascularization.
      The rarity of this disorder has limited research and the development of evidence
      based clinical management. While acknowledging these limitations, in this article
      the authors aim to summarize current studies of pediatric moyamoya, with the
      objective of providing a framework for construction of evidence-based guidelines
      for treatment. The compilation of current data in these guidelines should serve
      as a resource to aid pediatric neurosurgeons in their role as advocates for
      providing appropriate care to affected children.

PMID- 22462698
TI  - Editorial: shunt failure.

PMID- 22462699
TI  - Parental recognition of shunt failure: a prospective single-institution study.
AB  - OBJECT: Because there is no gold standard for preoperative diagnosis of shunt
      failure, understanding the sensitivity, specificity, and predictive values of
      symptoms, signs, and diagnostic tests enables practitioners to make logical
      clinical decisions. Parents of children with shunts undergo educational
      instruction to enable them to recognize shunt failure. The authors prospectively
      investigated parental ability to recognize shunt failure. METHODS: Data were
      prospectively collected on 205 consecutive encounters in 153 children with
      shunted hydrocephalus presenting to the emergency department or clinic, or as an
      inpatient consultation, to the Children's Hospital of Alabama between April and
      October 2010. Regardless of the complaint, all parents were asked if they
      believed the shunt was in failure. Six children were excluded from analysis
      because a parental response was lacking. Using the Shunt Design Trial
      definitions, shunt failure was diagnosed intraoperatively or ruled out if the
      child did not undergo shunt revision within 1 week of presentation. Sensitivity,
      specificity, predictive values, and accuracy were calculated using the parental
      response and shunt failure diagnosis. Secondarily, parents were compared based on
      their experience with shunt failure in their children; experienced parents were
      defined as having experienced at least 3 shunt failures. Post hoc analysis
      evaluated diagnostic test characteristics among hydrocephalus causes and compared
      parental recognition of shunt failure to head CT and shunt series diagnostic test
      characteristics. Parents also completed a standardized shunt failure survey
      regarding their shunt teaching education and symptom tracking. RESULTS: Children
      enrolled were a mean age of 6.9 years old, 92 (46%) of the encounters were with
      male patients, and most patients were Caucasian (69%) and had undergone an
      average of 2.8 previous shunt revisions. Seventy-one children (36%) were
      diagnosed with shunt failure. Parental response diagnostic test characteristics
      were: positive predictive value (PPV) of 41%, negative predictive value (NPV) of
      79%, sensitivity of 83%, specificity of 34%, and accuracy of 52% for shunt
      failure. Sixty-three parents were considered experienced and responded with a PPV
      of 29%, NPV of 92%, sensitivity of 94%, specificity of 23%, and accuracy of 41%.
      One hundred thirty-six parents were considered inexperienced and responded with a
      PPV of 48%, NPV of 75%, sensitivity of 80%, specificity of 41%, and accuracy of
      57%. When statistically compared, experienced parents had significantly lower PPV
      (29% vs 48%, respectively; p = 0.035) and accuracy (41% vs 57%, respectively; p =
      0.049) than inexperienced parents. On post hoc analysis, parental recognition of
      shunt failure was inferior to head CT and shunt series diagnostic tests with a
      lower specificity (20% vs 88%, respectively; p < 0.0005), PPV (44% vs 84%,
      respectively; p < 0.0005), NPV (61% vs 85%, respectively; p = 0.006), and
      accuracy (47% vs. 85%, respectively; p < 0.0005). CONCLUSIONS: The overall
      parental response had the greatest value in ruling out shunt failure, reflected
      in the high NPV, particularly in experienced parents. The head CT and shunt
      series provide more favorable diagnostic test characteristics than the parental
      response. Although educational interventions have decreased shunt-related deaths,
      parents have difficulty differentiating shunt failure from alternative diagnoses.

PMID- 22462700
TI  - Clinical, radiological, and genetic similarities between patients with Chiari
      Type I and Type 0 malformations.
AB  - OBJECT: Although Chiari Type I (CM-I) and Type 0 (CM-0) malformations have been
      previously characterized clinically and radiologically, there have been no
      studies focusing on the possible genetic link between these disorders. The goal
      of this study was to identify families in whom CM-0 and CM-I co-occurred and to
      further assess the similarities between these disorders. METHODS: Families were
      ascertained through a proband with CM-I. Detailed family histories were obtained
      to identify first-degree relatives diagnosed with CM-0. Several criteria were
      used to exclude individuals with acquired forms of CM-I and/or syringomyelia.
      Individuals were excluded with syndromic, traumatic, infectious, or tumor-related
      syringomyelia, as well as CM-I due to a supratentorial mass, hydrocephalus,
      history of cervical or cranial surgery unrelated to CM-I, or development of
      symptoms following placement of a lumbar shunt. Medical records and MR images
      were used to characterize CM-I and CM-0 individuals clinically and
      radiologically. RESULTS: Five families were identified in which the CM-I proband
      had a first-degree relative with CM-0. Further assessment of affected individuals
      showed similar clinical and radiological features between CM-0 and CM-I
      individuals, although CM-I patients in general had more severe symptoms and skull
      base abnormalities than their CM-0 relatives. Overall, both groups showed
      improvement in symptoms and/or syrinx size following craniocervical decompression
      surgery. CONCLUSIONS: There is accumulating evidence suggesting that CM-0 and CM
      I may be caused by a common underlying developmental mechanism. The data in this
      study are consistent with this hypothesis, showing similar clinical and
      radiological features between CM-0 and CM-I individuals, as well as the
      occurrence of both disorders within families. Familial clustering of CM-0 and CM
      I suggests that these disorders may share an underlying genetic basis, although
      additional epigenetic and/or environmental factors are likely to play an
      important role in the development of CM-0 versus CM-I.

PMID- 22462701
TI  - Editorial: Hemispherotomy.

PMID- 22462702
TI  - Palliative hemispherotomy in children with bilateral seizure onset.
AB  - OBJECT: Intractable epilepsy is a significant burden on families and on the
      cognitive development and quality of life (QOL) of patients. Periinsular
      hemispherotomy (PIH) for medically intractable epilepsy can benefit patients who
      qualify for this procedure. The ideal hemispherotomy candidate has ipsilateral
      ictal and interictal epileptiform activity, unilateral MR imaging abnormalities,
      contralateral hemiplegia, and a normal contralateral hemisphere. However, certain
      patients present with a mixed picture of bilateral electroencephalography (EEG)
      findings and severe intractable epilepsy, prompting consideration of a more
      aggressive treatment approach. This report introduces the possibility of surgery
      for patients who normally would not meet criteria for this treatment modality.
      METHODS: In this retrospective chart review, the authors report on 7 patients
      with bilateral seizure onset noted on routine or video-EEG monitoring. A QOL
      phone questionnaire, based on the Quality of Life in Childhood Epilepsy tool, was
      administered to a parent. The authors reviewed each patient's chart for surgical
      complications, changes in examination, QOL, limited neuropsychological outcomes,
      and seizure outcomes. They also investigated each chart for MR imaging and EEG
      findings as well as the patient's epilepsy clinic notes for seizure semiology and
      frequency. RESULTS: All patients enjoyed a decrease in seizure frequency and a
      subjective increase in QOL after PIH. Five patients (71%) achieved Engel Class I
      or II seizure control. The mean follow-up was 3.64 years (2-5.3 years). One
      patient is now off all antiseizure medication. No patient had a decrement in Full
      Scale IQ on postsurgical testing, and 2 (28.5%) of 7 individuals had increased
      adaptive and social functioning. Postsurgical examination changes included
      hemiplegia and homonymous hemianopia. CONCLUSIONS: Hemispherotomy in patients
      with intractable epilepsy is generally reserved for individuals with unilateral
      epileptiform abnormalities or lesions on MR imaging. Seven patients in this study
      benefited from surgery despite bilateral seizure onset with improvement in
      seizure control and overall QOL. Thus, bilateral ictal onset does not necessarily
      preclude consideration for hemispherotomy in selected patients with severe
      medically refractory epilepsy.

PMID- 22462703
TI  - Intractable episodic bradycardia resulting from progressive lead traction in an
      epileptic child with a vagus nerve stimulator: a delayed complication.
AB  - Vagus nerve stimulation (VNS) is used as palliation for adult and pediatric
      patients with intractable epilepsy who are not candidates for curative resection.
      Although the treatment is generally safe, complications can occur
      intraoperatively, perioperatively, and in a delayed time frame. In the
      literature, there are 2 reports of pediatric patients with implanted VNS units
      who had refractory bradycardia that resolved after the stimulation was turned
      off. The authors report the case of a 13-year-old boy with a history of vagus
      nerve stimulator placement at 2 years of age, who developed intractable episodic
      bradycardia that persisted despite the cessation of VNS and whose imaging results
      suggested vagus nerve tethering by the leads. He was subsequently taken to the
      operating room for exploration, where it was confirmed that the stimulator lead
      was exerting traction on the vagus nerve, which was displaced from the carotid
      sheath. After the vagus nerve was untethered and the leads were replaced, the
      bradycardia eventually resolved with continual effective VNS therapy. When
      placing a VNS unit in a very young child, accommodations must be made for years
      of expected growth. Delayed intractable bradycardia can result from a vagus nerve
      under traction by tethered stimulator leads.

PMID- 22462704
TI  - Vasculopathy after intracystic bleomycin administration for a recurrent cystic
      craniopharyngioma: case report.
AB  - Intracystic bleomycin (ICB) administration is known to be effective in the
      treatment of cystic craniopharyngiomas (CRPs) and rarely causes serious
      complications. The authors report a case of vasculopathy after ICB injection for
      a recurrent cystic CRP. A 5-year-old boy presented with the cystic recurrence of
      a CRP. A catheter and Ommaya system were inserted into the cyst, followed by a
      leakage test 2 weeks later. Bleomycin was delivered at 3 mg per week for 14 weeks
      (total dose 42 mg). Four months later, the patient's activity decreased and right
      hemiparesis occurred. Magnetic resonance imaging and cerebral angiography
      demonstrated a recurrent multicystic mass and infarction at the left middle
      cerebral artery territory with stenosis/occlusion of the left distal internal
      carotid artery and posterior cerebral artery. During the operation to remove the
      recurrent cystic mass, fibrotic stenoocclusion of the left intracranial arteries
      was identified. The cyst was totally removed. However, additional multiple border
      zone infarctions occurred in the left hemisphere, and the patient became
      wheelchair bound. Leakage of ICB was considered as the most probable cause of the
      cerebral vasculopathy and corresponding infarction. A leakage test may not always
      guarantee a leakage-free status even if the test is negative. Direct bypass
      surgery should have been considered to prevent a high risk of postoperative
      infarction in this case of a recurrent CRP with confirmed vasculopathy.

PMID- 22462705
TI  - Atypical teratoid/rhabdoid tumor with 26-year overall survival: case report.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive embryonic brain tumor
      predominantly seen in young children. The authors report an unusual case of a
      fourth ventricle AT/RT in an infant who survived for 26 years. The tumor was
      resected when the patient was 6 months of age, and radiation therapy (40-Gy total
      dose) was performed thereafter. The patient was free from the disease for 26
      years until a recurrent tumor was found in the spinal cord. The spinal cord
      neoplasm was a "collision tumor" with 2 components: benign schwannoma and
      recurrent AT/RT. The patient died of dissemination of the recurrent tumor 5
      months after it was excised. This is the longest survival of a patient with AT/RT
      ever reported and indicates that long-term survival, more than 20 years, can be
      achieved in infantile-onset AT/RT. Despite intensive treatment, the prognosis for
      AT/RT is very poor, especially in children younger than 3 years of age. The
      benefits of upfront radiation therapy for AT/RT should be carefully assessed with
      respect to its inevitable toxicity in very young children. However, early upfront
      radiation therapy may be of therapeutic interest to prevent aggressive
      progression of the disease.

PMID- 22462706
TI  - Intraventricular lesions in tuberous sclerosis complex: a possible association
      with the caudate nucleus.
AB  - OBJECT: Tuberous sclerosis complex (TSC) can manifest with 3 principal
      intracranial pathological entities: cortical tubers, subependymal nodules (SENs),
      and subependymal giant cell astrocytomas (SEGAs). The authors analyzed the
      location and growth of intraventricular lesions in a large cohort of patients
      with TSC. METHODS: After institutional review board protocol approval, the
      authors retrospectively reviewed brain MRI scans of TSC patients for whom at
      least 1 electronically stored cranial MRI study was available. Collected data
      included location, size, and growth over time of all intraventricular lesions.
      RESULTS: The authors reviewed 560 scans in 103 patients, who harbored 496
      intraventricular lesions. Of the 496 lesions, 157 lesions were located along the
      caudate-thalamic groove (CTG) in 88 patients. Twenty SEGAs were operated on. The
      remaining 339 lesions were distributed along the lateral ventricle, always in
      contact with the course of the caudate nucleus, and were presumed to be SENs.
      Twenty-two patients with more than 4 years of follow-up had 34 lesions along the
      CTG, of which 23 were stable in size and 11 grew. All other intraventricular
      lesions were stable. Seven-Tesla MRI showed the intimate association of SENs and
      the caudate nucleus in 1 patient. CONCLUSIONS: Intraventricular lesions in TSC
      patients are located throughout the lateral ventricular wall. Their location
      exclusively follows the course of the caudate nucleus. Only lesions along the CTG
      showed the potential to grow, and these were then identified as SEGAs. The
      remaining lesions were SENs. Understanding why these lesions develop in relation
      to the caudate nucleus may offer insights into therapy.

PMID- 22462707
TI  - Subdural hemorrhage as a first symptom in an infant with a choledochal cyst: case
      report.
AB  - Choledochal cysts are not rare in East Asia. The classic symptoms of these cysts
      are intermittent abdominal pain, jaundice, and a right upper quadrant abdominal
      mass. The authors report the case of an infant with a choledochal cyst presenting
      with intracranial hemorrhage. This 2-month-old girl with a partial coma presented
      at the authors' hospital. A brain CT scan revealed right-sided subdural
      hemorrhage. The routine preoperative survey found coagulopathy. After correcting
      the bleeding disorder, an emergency craniectomy was performed. Further
      examination found a choledochal cyst during abdominal ultrasonography and CT.
      Choledochal cysts are a cause of neonatal cholestasis but rarely produce vitamin
      K deficiency bleeding.

PMID- 22462708
TI  - Stereotactic endoscopic resection and surgical management of a subependymal giant
      cell astrocytoma: case report.
AB  - Subependymal giant cell astrocytomas (SEGAs) are benign tumors, most commonly
      associated with tuberous sclerosis complex (TSC). Arising from the lateral
      ependymal surface, these tumors may obstruct one or both foramina of Monro,
      resulting in hydrocephalus and often requiring treatment. Although
      interhemispheric-transcallosal and transcortical-transventricular approaches have
      been the standard methods for resecting these tumors, advances in neuroendoscopic
      techniques have expanded SEGAs as a potential target for endoscopic resection.  
      The authors present a case of an endoscopically resected SEGA with stereotactic
      guidance in a 4-year-old girl with TSC. A gross-total resection of an enlarging
      SEGA was achieved. This represents one of the early case reports of
      endoscopically resected SEGAs. Although recent advances in medical treatment for
      SEGAs with mammalian target of rapamycin (mTOR) pathway inhibitors have shown
      promising initial results, the long-term safety and efficacy of mTOR inhibitors
      has yet to be determined. The propensity of these tumors to cause obstructive
      hydrocephalus requires that a surgical option remain. Neuroendoscopic approaches
      may allow a safe and effective technique.

PMID- 22462709
TI  - Cerebrospinal fluid shunting and hearing loss in patients treated for
      medulloblastoma.
AB  - OBJECT: Cerebrospinal fluid shunting has previously been associated with hearing
      loss. Although the mechanism for this is unclear, it is thought that changes in
      CSF pressure can affect cochlear physiology via endolymph expansion in the
      setting of a patent cochlear aqueduct. Patients undergoing radiation and
      cisplatin chemotherapy are at risk for hearing loss. The authors hypothesized
      that the incidence and severity of hearing loss in patients undergoing radiation
      and chemotherapy for medulloblastoma would be greater in those with shunts than
      in those without shunts. METHODS: Baseline and longitudinal audiology data were
      collected in 33 patients with medulloblastoma who were receiving radiation and
      cisplatin chemotherapy. Additional data included age, sex, details of shunt
      placement and revision, and details of chemotherapy and radiation. Hearing
      sensitivity and peripheral auditory function measures included pure tone
      audiometry, immittance audiometry, and distortion product evoked otoacoustic
      emissions. Ototoxicity was determined according to the American Speech-Language
      Hearing Association criteria. Severity of hearing loss was determined using the
      Brock hearing loss grades. Incidence of hearing loss and association with
      shunting was determined. RESULTS: Thirteen (39.4%) of the 33 patients evaluated
      had undergone shunt placement. Hearing loss occurred in 14 (70%) of 20 patients
      without shunts and in 13 (100%) of 13 patients with shunts. The difference
      between the rates of hearing loss in patients with shunts versus those without
      the devices was highly significant (p = 0.0008). The odds ratio for hearing loss
      in patients with a CSF shunt compared with those without a shunt was 23.49 (95%
      CI 4.21-131.15). Age, side of shunt, evidence of dissemination, diameter of
      cochlear aqueduct, and treatment protocol did not have a significant effect on
      shunt-related ototoxicity. CONCLUSIONS: This study suggests an independent
      association between CSF shunting and hearing loss in children undergoing
      treatment for medulloblastoma, laying the foundation for a prospective study
      evaluating hearing loss in children with shunts who are not treated with ototoxic
      therapy.

PMID- 22462710
TI  - Efficacy of indocyanine green videography and real-time evaluation by FLOW 800 in
      the resection of a spinal cord hemangioblastoma in a child: case report.
AB  - A 19-month-old child was gradually suffering from gait disturbance and was
      referred by his pediatrician to the authors' institution. Spinal MRI showed Gd
      enhanced spinal cord tumor and congestive myelopathy. Intraoperatively the lesion
      was seen to be a hemangioblastoma. Because discrimination of the arterialized
      draining veins from the feeding arteries was difficult, indocyanine green
      videography was conducted to differentiate them. Real-time evaluation by FLOW 800
      revealed that the slope of the average signal intensity in the feeding artery was
      steeper than that of the arterialized veins. The tumor was successfully resected,
      and postoperative indocyanine green videography showed total removal of the tumor
      as a signal-negative region; the circulation time between the feeding artery and
      the main draining vein was prolonged from 2.5 to 5.5 seconds. Indocyanine green
      videography and real-time evaluation by FLOW 800 were objective and effective for
      the excision of a tumor retaining the arteriovenous shunt. The patient recovered
      from congestive myelopathy and gait disturbance.

PMID- 22462711
TI  - Spinal arachnoid cysts in the pediatric population: report of 31 cases and a
      review of the literature.
AB  - OBJECT: The goal of this study was to review all cases of pediatric spinal
      arachnoid cysts (SACs) surgically treated at the authors' institution between
      1992 and 2008 and to compare these cases to the published literature for the
      general population. METHODS: The charts of all pediatric patients with SACs were
      reviewed for demographics, medical history, presenting symptoms, imaging
      findings, operative procedure(s), complications, and outcomes. Following a
      complete literature review, the pediatric data were compared with data from the
      general population and unique findings associated with pediatric patients were
      identified. RESULTS: Thirty-one pediatric patients (median age 6.9 years)
      underwent operative intervention for SACs between 1992 and 2008 (median duration
      of follow-up 4.2 years). There were 17 female patients (55%) and 14 male patients
      (45%). Twenty-one patients (68%) presented with symptoms of radiculopathy or
      myelopathy. The most common presenting symptoms were pain (42%), lower-extremity
      weakness (39%), gait instability (32%), spasticity (19%), sensory loss (10%), and
      bladder dysfunction (7%). In 3 patients (10%) SACs were incidental findings.
      Intradural SACs were more common (18 patients, 58%) than extradural SACs (11
      patients, 36%). One patient (3%) had extradural and intradural components. One
      patient (3%) had a purely intramedullary cyst, and 1 patient (3%) had both an
      intradural and intramedullary component. Of the 18 intradural SACs, 9 (50%) were
      located ventral to the spinal cord and 9 (50%) were dorsally situated. One dorsal
      intradural SAC had an intramedullary component. All extradural SACs were located
      dorsal to the spinal cord. Intradural SACs were primarily concentrated in the
      cervical and thoracic regions (67%), whereas extradural cysts were more evenly
      distributed between the thoracic, lumbar, and sacral regions. Of the 18 patients
      with intradural SACs, 13 (72%) had significant previous CNS abnormalities,
      compared with 3 (27%) of 11 patients with extradural SACs. There were 2 operative
      complications. One patient had a CSF leak treated with a lumbar drain, and the
      second patient had a pseudomeningocele. No patients had neurological
      deterioration as a result of surgical intervention. Twenty-one patients (68%) had
      complete remission of symptoms, 6 (19%) had improvement, 3 (10%) were stable, and
      1 (3%) has worsening of symptoms with recurrence that ultimately required
      cystoperitoneal shunting, despite multiple failed attempts at fenestration.
      CONCLUSIONS: Spinal arachnoid cysts are rare lesions in the pediatric population.
      Affected patients present with back pain, weakness, and/or gait instability. In
      children, SACs predominantly develop in the thoracic region and are more likely
      to occur intradurally, compared with SACs in the general population. Overall
      outcomes following surgical fenestration or excision of SACs are excellent, with
      complete remission or improvement of symptoms achieved in 87% of cases.

PMID- 22462712
TI  - Absorbable anterior cervical plate for corpectomy and fusion in a 2-year-old
      child with neurofibromatosis. Technical note.
AB  - Postlaminectomy cervical kyphosis is one of the most challenging entities in
      spine surgery. Correction of this deformity usually requires anterior fusion with
      plating and a strut graft or interbody cage and posterior fusion with screws and
      rods. The situation is more complicated in the young child because fusion may
      affect future growth of the cervical spine. There is also a paucity of adequate
      instrumentation for the small bony structures. Some authors have reported
      utilization of absorbable cervical plates for fusion in pediatric patients with
      favorable results.   The authors present a modified surgical technique that was
      used for circumferential fusion in a 2-year-old girl with cervical kyphosis and
      recurrent neurofibroma. Anterior fusion was performed using an autologous rib
      graft and an absorbable cervical plate. This was followed by posterior fusion
      using rib bone and cables. Previous reports on the use of absorbable cervical
      plates are reviewed and the advantages of the current technique are discussed.

PMID- 22462713
TI  - Surgical treatment of thoracic Pott disease in a 3-year-old child, with vertebral
      column resection and posterior-only circumferential reconstruction of the spinal
      column: case report.
AB  - Tuberculosis (TB) is a common disease worldwide that is caused by Mycobacterium
      tuberculosis. Tuberculosis of the spine, also called Pott disease, is the most
      common site of bony dissemination. Although children are disproportionately
      affected, spinal TB is nonetheless rare in very young children. Cases involving
      infants requiring surgical intervention have been previously reported, and they
      are often associated with greater management challenges given the technical
      difficulty with instrumentation in very young children.   This case involved a 3
      year-old girl with TB centered at T-6, who presented with myelopathy from spinal
      cord compression and a severe kyphotic deformity (> 60 degrees ). She underwent a
      single-stage costotransversectomy for vertebral column resection, followed by
      reconstruction with an anterior expandable titanium cage and posterior pedicle
      screw instrumentation. At last follow-up, the patient was clinically and
      radiographically stable.   The authors report on the youngest patient with spinal
      TB treated surgically with this strategy and review the literature regarding
      prior cases involving young children. Although limited by the paucity of cases in
      the literature, surgical debridement and spinal fusion appear to provide a safe
      alternative to prolonged bed rest or casting and may offer additional benefits of
      a faster recovery and ambulation.

PMID- 22462714
TI  - Neural activity generated in the neural placode and nerve roots in the neonate
      with spina bifida.
AB  - OBJECT: The authors conducted a study to determine the neurophysiological
      capacity of the neural placode in spina bifida neonates and to determine if the
      spinal nerve roots in these neonates had normal stimulation. METHODS: The authors
      present a case series of 2 neonates born with open neural tube defects who
      underwent neural tube closure within 24 hours of birth. Neurophysiological
      monitoring and electrical stimulation of the placode and nerve roots was
      performed before and after closure of the neural tube. RESULTS: Stimulation of
      nerve roots resulted in evoked electromyographic responses in distinct muscle
      groups, indicative of the myotome innervation pattern. Stimulation threshold did
      not change significantly after closure of the placode. Stimulation within the
      placode generated an alternating pattern of activity in the left and right legs.
      CONCLUSIONS: Closure of the neural tube did not affect the stimulation threshold
      of the nerve roots, which remained easily excitable. The viability of the nerve
      roots suggests that they may be candidates for neural prostheses in the future.
      The neural placode contains basic neural elements for generating a locomotor-like
      pattern in response to tonic neural inputs.

PMID- 22462715
TI  - Letter to the editor: dilution versus pollution.

PMID- 22462716
TI  - Letter to the editor: calvarial autograft.

PMID- 22462717
TI  - Letter to the editor: helmets and synostosis.

PMID- 22462718
TI  - Cancer disclosure: experiences of Iranian cancer patients.
AB  - This study explored Iranian patients' experiences of cancer disclosure, paying
      particular attention to the ways of disclosure. Twenty cancer patients were
      invited to participate in this qualitative inquiry by research staff in the
      clinical setting. In-depth, semistructured interview data were analyzed through
      content analysis. The rigor of the study was established by principles of
      credibility, transferability, dependability, and confirmability. Four themes
      emerged: the atmosphere of non-disclosure, eventual disclosure, distress in
      knowing, and the desire for information. Non-disclosure was the norm for
      participants, and all individuals involved made efforts to maintain an atmosphere
      of non-disclosure. While a select few were informed of their diagnosis by a
      physician or another patient, the majority eventually became aware of their
      diagnosis indirectly by different ways. All participants experienced distress
      after disclosure. The participants wanted basic information about their prognosis
      and treatments from their treating physicians, but did not receive this
      information, and encountered difficulty accessing information elsewhere. These
      challenges highlight the need for changes in current medical practice in Iran, as
      well as patient and healthcare provider education.

PMID- 22462719
TI  - Sodium tetrachloropalladate for diagnosing palladium sensitization.
AB  - BACKGROUND: Exposure to palladium (Pd) may lead to clinical allergic reactions.
      With frequent nickel (Ni) exposure and cross-reactivity between Ni and Pd at the
      T cell recognition level, positive Pd reactions on patch testing are surprisingly
      uncommon. PdCl(2) is often used for epicutaneous patch testing. OBJECTIVES: To
      compare the sensitivity and specificity of sodium tetrachloropalladate (Na(2)
      PdCl(4)) and PdCl(2) for Pd patch testing in metal-allergic patients and non
      allergic controls. METHODS: Twenty-six metal-allergic patients and 26 non
      allergic controls were selected on the basis of detailed medical histories. Patch
      test results were used to determine the diagnostic performance of the two Pd
      salts as compared with NiSO(4). RESULTS: With three outliers in both groups, the
      sensitivity/specificity were calculated to be 42%/96% for PdCl(2), 65%/92% for
      Na(2) PdCl(4) , and 77%/92% for NiSO(4). Furthermore, of all (n = 19) Na(2)
      PdCl(4) reactors, 17 (89%) also showed positive reactions to NiSO(4). Conversely,
      of all (n = 22) NiSO(4) reactors, 17 (77%) showed concomitant positive reactions
      to Na(2) PdCl(4) . CONCLUSIONS: Positive test reactions to Na(2) PdCl(4) are
      confirmed by large-scale concordant reactions to PdCl(2) and NiSO(4). Although
      statistical significance was not reached, the increased sensitivity has important
      clinical relevance, as false-positive results are rare. Incorporation of Na(2)
      PdCl(4) into standard and/or dental screening patch test series is suggested.

PMID- 22462720
TI  - Application of a standardized anatomical classification in a Chinese partial
      nephrectomy series.
AB  - OBJECTIVE: Preoperative aspects and dimensions used for an anatomical
      classification is a standardized system to assess the anatomical complexity of
      renal tumors and its impact on perioperative outcomes of partial nephrectomy. The
      objective is to apply the preoperative aspects and dimensions used for an
      anatomical classification in a series of Chinese patients undergoing open or
      laparoscopic partial nephrectomy. METHODS: A total of 195 consecutive renal
      tumors treated with open partial nephrectomy or laparoscopic partial nephrectomy
      between June 2008 and May 2011 were included in this analysis. All the
      preoperative images and clinical records were retrospectively evaluated.
      Complication rate, warm ischemia time, operation time and degree of blood loss
      were compared among different risk groups (low risk: preoperative aspects and
      dimensions used for an anatomical score 6-7; intermediate risk: preoperative
      aspects and dimensions used for an anatomical score 8-9; high risk: preoperative
      aspects and dimensions used for an anatomical score >=10). The original
      preoperative aspects and dimensions used for an anatomical score system was
      modified by replacing rim location with hilar vasculature involvement and tested
      for prediction of overall complications. RESULTS: The median preoperative aspects
      and dimensions used for an anatomical score was 8. Overall complication rate was
      17.9%. Preoperative aspects and dimensions used for an anatomical score was an
      independent predictor for perioperative complications. Intermediate and high-risk
      patients had a four- and 37-fold higher risk of complications respectively (P =
      0.012, P < 0.001). Higher preoperative aspects and dimensions used for an
      anatomical score predicted longer operation time (P = 0.007), warm ischemia time
      (P < 0.001) and higher degree of blood loss (P = 0.003) in open partial
      nephrectomy patients. In laparoscopic partial nephrectomy patients, preoperative
      aspects and dimensions used for an anatomical score was also a predictor for warm
      ischemia time (P = 0.033); however, it was not significant for operation time and
      degree of blood loss (P = 0.325, P = 0.302). The modified preoperative aspects
      and dimensions used for an anatomical score was an independent predictor for
      overall complications (P < 0.001); however, its superiority could not be verified
      (P = 0.847). CONCLUSIONS: The preoperative aspects and dimensions used for an
      anatomical classification predicts the risk of overall complications in Chinese
      patients undergoing nephron-sparing surgery. Replacing the rim location with
      hilar vasculature involvement might be a promising modification of this scoring
      system.

PMID- 22462721
TI  - Widespread horizontal genomic exchange does not erode species barriers among
      sympatric ducks.
AB  - BACKGROUND: The study of speciation and maintenance of species barriers is at the
      core of evolutionary biology. During speciation the genome of one population
      becomes separated from other populations of the same species, which may lead to
      genomic incompatibility with time. This separation is complete when no fertile
      offspring is produced from inter-population matings, which is the basis of the
      biological species concept. Birds, in particular ducks, are recognised as a
      challenging and illustrative group of higher vertebrates for speciation studies.
      There are many sympatric and ecologically similar duck species, among which
      fertile hybrids occur relatively frequently in nature, yet these species remain
      distinct. RESULTS: We show that the degree of shared single nucleotide
      polymorphisms (SNPs) between five species of dabbling ducks (genus Anas) is an
      order of magnitude higher than that previously reported between any pair of
      eukaryotic species with comparable evolutionary distances. We demonstrate that
      hybridisation has led to sustained exchange of genetic material between duck
      species on an evolutionary time scale without disintegrating species boundaries.
      Even though behavioural, genetic and ecological factors uphold species boundaries
      in ducks, we detect opposing forces allowing for viable interspecific hybrids,
      with long-term evolutionary implications. Based on the superspecies concept we
      here introduce the novel term "supra-population" to explain the persistence of
      SNPs identical by descent within the studied ducks despite their history as
      distinct species dating back millions of years. CONCLUSIONS: By reviewing
      evidence from speciation theory, palaeogeography and palaeontology we propose a
      fundamentally new model of speciation to accommodate our genetic findings in
      dabbling ducks. This model, we argue, may also shed light on longstanding
      unresolved general speciation and hybridisation patterns in higher organisms,
      e.g. in other bird groups with unusually high hybridisation rates. Observed
      parallels to horizontal gene transfer in bacteria facilitate the understanding of
      why ducks have been such an evolutionarily successful group of animals. There is
      large evolutionary potential in the ability to exchange genes among species and
      the resulting dramatic increase of effective population size to counter selective
      constraints.

PMID- 22462723
TI  - Three-dimensional electrospun poly(lactide-co-E-caprolactone) for small-diameter
      vascular grafts.
AB  - Nanofibers have been applied to tissue engineering scaffolds because fiber
      diameters are of the same scale as the physical structure of protein fibrils in
      the native extracellular matrix. In this study, we utilized cell matrix
      engineering combined with cell sheet matrix and electrospinning technologies. We
      studied small-diameter vascular grafts in vitro by seeding smooth muscle cells
      onto electrospun poly(lactide-co-E-caprolactone) (PLCL) scaffolds, culturing and
      constructing a three-dimensional network. The vascular grafts constructed using
      cell matrix engineering were similar to the native vessels in their mechanical
      properties, such as tensile strength, tensile strain, and e-modulus. Also, they
      had a self-sealing property more improved than GORE-TEX because PLCL has
      compatible elasticity. Small-diameter vascular grafts constructed using matrix
      engineering have the potential to be suitable for vascular grafts.

PMID- 22462722
TI  - Circulating endocannabinoid concentrations and sexual arousal in women.
AB  - INTRODUCTION: Several lines of evidence point to the potential role of the
      endocannabinoid system in female sexual functioning. These include results from
      studies describing the subjective effects of exogenous cannabinoids on sexual
      functioning in humans and the observable effects of exogenous cannabinoids on
      sexual functioning in other species, as well as results from studies
      investigating the location of cannabinoid receptors in the brain and periphery,
      and the effects of cannabinoid receptor activation on neurotransmitters
      implicated in sexual functioning. While these lines of research suggest a role
      for the endocannabinoid system in female sexual functioning, no studies
      investigating the relationship between concentrations of endogenous cannabinoids
      (i.e., arachidonoylethanolamide [AEA] and 2-arachidonoylglycerol [2-AG]) and
      sexual functioning have been conducted in any species. AIM: To measure
      circulating endocannabinoid concentrations in relation to subjective and
      physiological indices of sexual arousal in women (N = 21). METHODS: Serum
      endocannabinoid (AEA and 2-AG) concentrations were measured immediately prior to,
      and immediately following, viewing of neutral (control) and erotic (experimental)
      film stimuli in a repeated measures design. Physiological sexual arousal was
      measured via vaginal photoplethysmography. Subjective sexual arousal was measured
      both continuously and noncontinuously. Pearson's correlations were used to
      investigate the relationships between endocannabinoid concentrations and sexual
      arousal. MAIN OUTCOME MEASURES: Changes in AEA and 2-AG concentrations from pre-
      to post-film and in relation to physiological and subjective indices of sexual
      arousal. RESULTS: Results revealed a significant relationship between
      endocannabinoid concentrations and female sexual arousal, whereby increases in
      both physiological and subjective indices of sexual arousal were significantly
      associated with decreases in AEA, and increases in subjective indices of sexual
      arousal were significantly associated with decreases in 2-AG. CONCLUSIONS: These
      findings support the hypothesis that the endocannabinoid system is involved in
      female sexual functioning, with implications for furthering understanding of the
      biological mechanisms underlying female sexual functioning.

PMID- 22462724
TI  - Identification of protein targets of reactive metabolites of tienilic acid in
      human hepatocytes.
AB  - Tienilic acid (TA) is a uricosuric diuretic that was withdrawn from the market
      only months after its introduction because of reports of serious incidents of
      drug-induced liver injury including some fatalities. Its hepatotoxicity is
      considered to be primarily immunoallergic in nature. Like other thiophene
      compounds, TA undergoes biotransformation to a S-oxide metabolite which then
      reacts covalently with cellular proteins. To identify protein targets of TA
      metabolites, we incubated [(14)C]-TA with human hepatocytes, separated cellular
      proteins by 2D gel electrophoresis, and analyzed proteins in 36 radioactive spots
      by tryptic digestion followed by LC-MS/MS. Thirty-one spots contained at least
      one identifiable protein. Sixteen spots contained only one of 14 nonredundant
      proteins which were thus considered to be targets of TA metabolites. Six of the
      14 were also found in other radioactive spots that contained from 1 to 3
      additional proteins. Eight of the 14 had not been reported to be targets for any
      reactive metabolite other than TA. The other 15 spots each contained from 2 to 4
      identifiable proteins, many of which are known targets of other chemically
      reactive metabolites, but since adducted peptides were not observed, the identity
      of the adducted protein(s) in these spots is ambiguous. Interestingly, all the
      radioactive spots corresponded to proteins of low abundance, while many highly
      abundant proteins in the mixture showed no radioactivity. Furthermore, of
      approximately 16 previously reported protein targets of TA in rat liver (   
      Methogo, R., Dansette, P., and Klarskov, K.     (  2007  )   Int. J. Mass
      Spectrom. ,  268  ,   284 -295   ), only one (fumarylacetoacetase) is among the
      14 targets identified in this work. One reason for this difference may be
      statistical, given that each study identified a small number of targets from
      among thousands present in hepatocytes. Another may be the species difference
      (i.e., rat vs human), and still another may be the method of detection of
      adducted proteins (i.e., Western blot vs C-14). Knowledge of human target
      proteins is very limited. Of more than 350 known protein targets of reactive
      metabolites, only 42 are known from humans, and only 21 of these are known to be
      targets for more than one chemical. Nevertheless, the demonstration that human
      target proteins can be identified using isolated hepatocytes in vitro should
      enable the question of species differences to be addressed more fully in the
      future.

PMID- 22462725
TI  - Oxygen measurements in platelet fluids - a new non-invasive method to detect
      bacterial contaminations in platelets.
AB  - BACKGROUND: The residual risk for bacterial contamination in blood components
      especially in platelets is one to two orders of magnitude higher than for
      transfusion relevant viral infections. The majority of all bacterial transmitted
      fatalities occurred at the end of platelet shelf life. Therefore, the maximum
      shelf life of platelet concentrates (PC) was reduced to 4 days after blood
      donation in Germany in 2008. METHODS: A new continuous non-invasive bacterial
      detection method was developed by O(2) measurements in the platelet fluids and
      tested with 10 transfusion relevant bacteria species. RESULTS: The bacterial
      concentration at the time point of a positive signal of PreSense O(2) ranged
      between 10(2) and 10(5) CFU mL(-1) . Harmful transfusion-transmitted bacterial
      infection would have probably been prevented by this novel technology. Only
      strict anaerobic bacteria strains like Clostridium perfringens were not detected
      within the study period of 72 h. CONCLUSIONS: The described non-invasive
      bacterial detection method represents a new approach to prevent transmission of
      bacterial infection in platelets. The method is characterised by the advantage
      that all investigations can be performed until right up to the time of
      transfusion, and therefore, reduce the risk for sample errors to a minimum.

PMID- 22462726
TI  - Preparation and magnetic properties of nano size nickel ferrite particles using
      hydrothermal method.
AB  - BACKGROUND: Nickel ferrite, a kind of soft magnetic materials is one of the most
      attracting class of materials due to its interesting and important properties and
      has many technical applications, such as in catalysis, sensors and so on. In this
      paper the synthesis of NiFe2O4 nanoparticles by the hydrothermal method is
      reported and the inhibition of surfactant (Glycerol or Sodium dodecyl sulfate) on
      the particles growth is investigated. METHODS: For investigation of the
      inhibition effect of surfactant on NiFe2O4 particles growth, the samples were
      prepared in presence of Glycerol and Sodium dodecyl sulfate. The X-ray powder
      diffraction (XRD), transmission electron microscopy (TEM), Fourier transform
      infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM) and
      inductively coupled plasma atomic emission spectrometer (ICP-AES) techniques were
      used to characterize the samples. RESULTS: The results of XRD and ICP-AES show
      that the products were pure NiFe2O4 and also nanoparticles grow with increasing
      the temperature, while surfactant prevents the particle growth under the same
      condition. The average particle size was determined from the Scherrer's equation
      and TEM micrographs and found to be in the range of 50-60 nm that decreased up to
      10-15 nm in presence of surfactant. The FT-IR results show two absorption bands
      near to 603 and 490 cm-1 for the tetrahedral and octahedral sites respectively.
      Furthermore, the saturated magnetization and coercivity of NiFe2O4 nanoparticles
      were in the range of 39.60 emu/g and 15.67 Qe that decreased for samples prepared
      in presence of surfactant. As well as, the nanoparticles exhibited a
      superparamagnetic behavior at room temperature. CONCLUSIONS: Nanosized nickel
      ferrite particles were synthesized with and without surfactant assisted
      hydrothermal methods. The results show that with increasing of temperature, the
      crystallinity of nanoparticles is increased. In the presence of surfactants, the
      crystallinity of NiFe2O4 nanoparticles decreased in comparison with surfactant-
      free prepared samples. All of the nickel ferrite nanoparticles were
      superparamagnetic at room temperature. GRAPHICAL

PMID- 22462727
TI  - In vitro and in vivo protection by melatonin against the decline of elongation
      factor-2 caused by lipid peroxidation: preservation of protein synthesis.
AB  - As organisms age, a considerable decrease in protein synthesis takes place in all
      tissues. Among the possible causes of the decline of translation in old animals
      are the modifications of elongation factor-2 (eEF-2). eEF-2 occupies an essential
      role in protein synthesis where it catalyzes the ribosomal translocation
      reaction. eEF-2 is particularly sensitive to increased oxidative stress. However,
      all oxidants do not affect eEF-2, only compounds that increase lipid
      peroxidation. As peroxides are unstable compounds, they decompose and generate a
      series of highly reactive compounds, including aldehydes malondialdehyde (MDA)
      and 4-hydroxynoenal (HNE). We have previously reported that hepatic eEF-2 forms
      adducts with low-molecular weight aldehydes, MDA and HNE. Therefore, the
      protection of eEF-2 must be specifically carried out by a compound with
      lipoperoxyl radical-scavenging features such as melatonin. In this article, we
      show the ability of melatonin to protect against the changes that occur in the
      eEF-2 under conditions of lipid peroxidation induced by cumene hydroperoxide
      (CH), a compound used experimentally to induce lipid breakdown. As experimental
      models, we used cultured cells and rats treated with this oxidant compound. eEF-2
      levels, adduct formation of this protein with MDA and HNE, and lipid peroxides
      were determined. In the cultured cells, protein synthesis rate was also measured.
      Our results show that melatonin prevented the molecular changes in eEF-2 and the
      decline in protein synthesis rate secondary to lipid peroxidation. The results
      also show that serum levels of several hormones were affected by CH-induced
      oxidative stress, which was partially or totally prevented by melatonin.

PMID- 22462728
TI  - Job discrimination against childhood cancer survivors in Japan: a cross-sectional
      survey.
AB  - BACKGROUND: The aim of this study was to investigate the policies to identify job
      discrimination by company recruiters against childhood cancer survivors in Japan.
      METHODS: We conducted a cross-sectional study using a mailed questionnaire for
      the Japanese companies that were divided into three groups: companies listed on
      the stock market, companies not listed on the stock market, and public offices.
      We randomly selected 2000 of the 4000 listed companies and 2500 of the 4300
      unlisted companies. We selected 47 public offices from prefectures and 17 from
      government ordinance-designated cities. Outcomes were health certificate
      requirements, how to treat past medical history and present illness, childhood
      cancer survivors' employment experience, and company's policy for evaluating
      applicants based on past medical history and present illness. RESULTS: Response
      rates were 17.7% for listed companies, 28.9% for unlisted companies, and 56.3%
      for public offices. A health certificate was required by 86% of listed companies,
      77% of unlisted companies, and 75% of public offices. However, 33% of listed
      companies and 36% of unlisted companies, and none of the public offices demanded
      it at the time of application. Small numbers of private companies (0.7% of listed
      companies and 1.0% of unlisted companies) and public offices (4%) reject
      applicants outright if they have a disease in their past medical history. Using
      multivariate analysis, we found that large companies and company policies were
      significantly associated with the demand for a health certificate at the time of
      job applications. CONCLUSIONS: In Japan, employment-related discrimination still
      occurs in a small number of companies and public offices.

PMID- 22462729
TI  - Levetiracetam may favorably affect seizure outcome after temporal lobectomy.
AB  - PURPOSE: To study the prognostic implications of antiepileptic drug (AED) use on
      seizure freedom following temporal lobe resections for intractable epilepsy.
      METHODS: Seizure outcome implications of epilepsy characteristics and AED use
      were studied in patients who underwent temporal lobectomy patients at the
      Cleveland Clinic between September 1995 and December 2006. Survival analysis and
      multivariate regression with Cox proportional hazard modeling were used. Complete
      seizure freedom was defined as a favorable outcome. KEY FINDINGS: Records of 312
      patients were analyzed (mean +/- standard deviation follow-up 3.5 +/- 1.7 years).
      The estimated probability of complete seizure freedom was 69% at 12 months (95%
      confidence interval [CI] 66-72%), and 48% at 36 months (95% CI 45-52%). The mean
      number of AEDs used per patient at the time of surgery was 1.78 (range 1-4),
      dropping to 1.02 at last follow-up (range 0-4). Following multivariate analysis,
      a lower preoperative seizure frequency and perioperative use of levetiracetam
      predicted a favorable outcome (risk ratio [RR] 0.62, 95% CI 0.43-0.89, and RR =
      0.57, 95% CI 0.39-0.83, respectively), whereas nonspecific pathology (RR 1.71,
      95% CI 1.15-2.47) and a higher number of AEDs used at the time of surgery
      correlated with higher rates of seizure recurrence (whole-model log-rank test p
      value < 0.0001). Better outcomes within the levetiracetam group were seen despite
      a higher proportion of several poor prognostic indicators within this patient
      group, and started as early as 4 months after surgery, gradually increasing to a
      15-20% survival advantage by 5 years. No similar outcome correlations were
      identified with another AED. SIGNIFICANCE: AED use may be a potential new
      modifiable seizure-outcome predictor after temporal lobectomy. This possible
      prognostic indicator is discussed in light of proposed seizure recurrence
      mechanisms.

PMID- 22462730
TI  - Structural Studies of Derivatives of Methinyltricobalt Enneacarbonyls. V. Crystal
      Structure of Bis(methinyltricobalt enneacarbonyl), [CCo(3)(CO)(9)](2).

PMID- 22462731
TI  - Deep and almost unbearable suffering: consequences of childhood sexual abuse for
      men's health and well-being.
AB  - Previous studies indicate that childhood sexual abuse can have extensive and
      serious consequences. The aim of this research was to do a qualitative study of
      the consequences of childhood sexual abuse for Icelandic men's health and well
      being. Phenomenology was the methodological approach of the study. Totally 14
      interviews were conducted, two per individual, and analysed based on the
      Vancouver School of Phenomenology. The main results of the study showed that the
      men describe deep and almost unbearable suffering, affecting their entire life,
      of which there is no alleviation in sight. The men have lived in repressed
      silence most of their lives and have come close to taking their own lives. What
      stopped them from committing suicide was revealing to others what happened to
      them which set them free in a way. The men experienced fear- or rage-based shock
      at the time of the trauma and most of them endured the attack by dissociation,
      disconnecting psyche and body and have difficulties reconnecting. They had
      extremely difficult childhoods, living with indisposition, bullying, learning
      difficulties and behavioural problems. Some have, from a young age, numbed
      themselves with alcohol and elicit drugs. They have suffered psychologically and
      physically and have had relational and sexual intimacy problems. The consequences
      of the abuse surfaced either immediately after the shock or many years later and
      developed into complex post-traumatic stress disorder. Because of perceived
      societal prejudice, it was hard for the men to seek help. This shows the great
      need for professionals to be alert to the possible consequences of childhood
      sexual abuse in their practice to reverse the damaging consequences on their
      health and well-being. We conclude that living in repressed silence after a
      trauma, like childhood sexual abuse, can be dangerous for the health, well-being
      and indeed the very life of the survivor.

PMID- 22462732
TI  - Barium isotope fractionation during experimental formation of the double
      carbonate BaMn[CO3](2) at ambient temperature.
AB  - In this study, we present the first experimental results for stable barium (Ba)
      isotope ((137)Ba/(134)Ba) fractionation during low-temperature formation of the
      anhydrous double carbonate BaMn[CO(3)](2). This investigation is part of an
      ongoing work on Ba fractionation in the natural barium cycle. Precipitation at a
      temperature of 21+/-1 degrees C leads to an enrichment of the lighter Ba isotope
      described by an enrichment factor of-0.11+/-0.060/00 in the double carbonate than
      in an aqueous barium-manganese(II) chloride/sodium bicarbonate solution, which is
      within the range of previous reports for synthetic pure BaCO (3) (witherite)
      formation.

PMID- 22462734
TI  - Halogen bonding for rational drug design and new drug discovery.
AB  - INTRODUCTION: A large number of drugs and drug candidates in clinical development
      contain halogen substituents. For a long time, only the steric and lipophilic
      contributions of halogens were considered when trying to exploit their effects on
      ligand binding. However, the ability of halogens to form stabilizing
      interactions, such as halogen bonding, hydrogen bonding and multipolar
      interactions, in biomolecular systems was revealed recently. Halogen bonding, the
      non-covalent interaction in which covalently bound halogens interact with Lewis
      bases, has now been utilized in the context of rational drug design. AREAS
      COVERED: The purpose of this review is to show how halogen bonding could be used
      in drug design, and in particular, to stimulate researchers to apply halogen
      bonding in lead optimization. This review article covers the recent advances
      relevant to halogen bonding in drug discovery and biological design over the past
      decade, including database survey of this interaction in protein-ligand
      complexes, molecular mechanical investigations of halogen bonding in drug
      discovery and applications of this interaction in the development of halogenated
      ligands as inhibitors and drugs for protein kinases, serine protease factor Xa,
      HIV reverse transcriptase and so on. EXPERT OPINION: Halogen bonding should
      intentionally be used as a powerful tool, comparable with hydrogen bonding, to
      enhance the binding affinity and also influence the binding selectivity. Rational
      design of new and potent inhibitors against therapeutic targets through halogen
      bonding continues to be an exciting area, which will be further elucidated with
      the combination of various experimental techniques and theoretical calculations
      in the forthcoming years.

PMID- 22462735
TI  - The concept of RNA-assisted protein folding: the role of tRNA.
AB  - We suggest that tRNA actively participates in the transfer of 3D information from
      mRNA to peptides--in addition to its well-known, "classical" role of translating
      the 3-letter RNA codes into the one letter protein code. The tRNA molecule
      displays a series of thermodynamically favored configurations during translation,
      a movement which places the codon and coded amino acids in proximity to each
      other and make physical contact between some amino acids and their codons
      possible. This specific codon-amino acid interaction of some selected amino acids
      is necessary for the transfer of spatial information from mRNA to coded proteins,
      and is known as RNA-assisted protein folding.

PMID- 22462736
TI  - Angiotensin peptides and nitric oxide in cardiovascular disease.
AB  - SIGNIFICANCE: The renin-angiotensin system (RAS) plays an important role in the
      normal control of cardiovascular and renal function in the healthy state and is a
      contributing factor in the development and progression of various types of
      cardiovascular diseases (CVD), including hypertension, diabetes, and heart
      failure. RECENT ADVANCES: Evidence suggests that a balance between activation of
      the ACE/Ang II/AT1 receptor axis and the ACE2/Ang-(1-7)/Mas receptor axis is
      important for the function of the heart, kidney, and autonomic nervous system
      control of the circulation in the normal healthy state. An imbalance in these
      opposing pathways toward the ACE/Ang II/AT1 receptor axis is associated with CVD.
      The key component of this imbalance with respect to neural control of the
      circulation is the negative interaction between oxidative and NO* mechanisms,
      which leads to enhanced sympathetic tone and activation in disease conditions
      such as hypertension and heart failure. CRITICAL ISSUES: The key mechanisms that
      disrupt normal regulation of Ang II and Ang-(1-7) signaling and promote
      pathogenesis of CVD at all organ levels remain poorly understood. The reciprocal
      relation between ACE and ACE2 expression and function suggests they are
      controlled interdependently at pre- and post-translational levels. Insights from
      neural studies suggest that an interaction between oxidative and nitrosative
      pathways may be key. FUTURE DIRECTIONS: The role of redox mechanisms in the
      control of expression and activity of RAS enzymes and Ang receptors may provide
      important insight into the function of local tissue RAS in health and disease.

PMID- 22462737
TI  - Molecular markers in plasmodium falciparum linked to resistance to anti-malarial
      drugs in samples imported from Africa over an eight-year period (2002-2010):
      impact of the introduction of artemisinin combination therapy.
AB  - BACKGROUND: Drug resistance is a major problem to control Plasmodium falciparum
      infection in endemic countries. During last decade, African countries have
      changed first-line treatment to artemisinin-based combinations therapy (ACT);
      sulphadoxine-pyrimethamine (SP) is recommended for Intermittent Preventive
      Therapy (IPT). Molecular markers related to P falciparum resistance were analysed
      for the period of transition from SP to ACT, in isolates imported from Africa.
      METHODS: A first group of samples was taken in the period between June 2002 and
      June 2006 (n = 113); a second group in the period between November 2008 and
      August 2010 (n = 46). Several alleles were analysed by nested PCR-RFLP: 51, 59,
      108, 164, in the pfdhfr gene; 436, 437, 540, 581, in the pfdhps gene; 86, 1246,
      in the pfmdr1 gene and 76, in the pfcrt gene. The prevalence of alleles in the
      groups was compared with the chi-squared or Fisher's exact tests. RESULTS: The
      pfdhfr N51I, C59R and S108N were over to 90% in the two groups; all samples had
      the I164. In the pfdhps, 437 G and 581 G, increased up to 80% and 10.9% (p =
      0.024), respectively in the second group. The 540 G decreases (24% to 16.%) and
      the 436A disappears at the end of the follow-up (p = 0.004) in the second group.
      The 76I-pfcrt stayed over 95% in the two groups. Prevalence of 86Y-pfmdr1
      decreased over eight years. CONCLUSIONS: Pharmacological pressure affects the
      resistance strains prevalence. As for SP, the disappearance of 436A and the
      decrease in 540 G suggest that these mutations are not fixed. On the other hand,
      studies carried out after ACT introduction show there was a selection of strains
      carrying the SNPs N86Y, D1246Y in pfmdr1. In this work, the prevalence of pfmdr1-
      D1246Y is increasing, perhaps as a result of selective pressure by ACT. Continued
      surveillance is essential to monitor the effectiveness of treatments.

PMID- 22462738
TI  - Capsaicin induces cycle arrest by inhibiting cyclin-dependent-kinase in bladder
      carcinoma cells.
AB  - OBJECTIVE: Capsaicin is a specialized agonist of transient receptor potential
      vanilloid type 1 Ca2(+) channel, a member of the vanilloid receptor family of
      cation channels. We aimed to investigate the effects of capsaicin on the
      proliferation and cell death of human bladder cancer cells. METHODS: Human
      bladder cancer cell line 5637 was cultured and the expression of transient
      receptor potential vanilloid type 1 verified by immunofluorescence and Western
      blot. Cells were given different disposals (different capsaicin concentration
      with/without pre-treating with capsazepine; capsazepine, acting as a competitive
      antagonist of capsaicin) to observe cell viability, cell cycle and cell death by
      3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow
      cytometry. The apoptosis indexes, such as intracellular production of reactive
      oxygen species and mitochondrial membrane potential were assessed to elucidate
      the potential mechanism of capsaicin effects in the cells. RESULTS: Capsaicin
      decreased the viability of 5637 cells in a dose-dependent way. The flow cytometry
      outcome showed that capsaicin blocked the cell cycle in the G0/G1 period. The
      Western blot of cyclin-dependent-kinase involved in G1/S transfer verified this.
      Meanwhile, increased reactive oxygen species production and decreased
      mitochondrial membrane potential were detected in capsaicin-treated groups.
      CONCLUSIONS: Capsaicin induces cell death through increased reactive oxygen
      species and decreased mitochondrial membrane potential. Furthermore, capsaicin
      inhibits the proliferation of 5637 bladder carcinoma cells by cycle arrest with
      the inhibition of CDK2, CDK4 and CDK6.

PMID- 22462739
TI  - Anthropogenic mortality on coral reefs in Caribbean Panama predates coral disease
      and bleaching.
AB  - Caribbean reef corals have declined precipitously since the 1980s due to regional
      episodes of bleaching, disease and algal overgrowth, but the extent of earlier
      degradation due to localised historical disturbances such as land clearing and
      overfishing remains unresolved. We analysed coral and molluscan fossil
      assemblages from reefs near Bocas del Toro, Panama to construct a timeline of
      ecological change from the 19th century-present. We report large changes before
      1960 in coastal lagoons coincident with extensive deforestation, and after 1960
      on offshore reefs. Striking changes include the demise of previously dominant
      staghorn coral Acropora cervicornis and oyster Dendrostrea frons that lives
      attached to gorgonians and staghorn corals. Reductions in bivalve size and
      simplification of gastropod trophic structure further implicate increasing
      environmental stress on reefs. Our paleoecological data strongly support the
      hypothesis, from extensive qualitative data, that Caribbean reef degradation
      predates coral bleaching and disease outbreaks linked to anthropogenic climate
      change.

PMID- 22462740
TI  - Just how feasible is pharmacogenetic testing in the primary healthcare setting?

PMID- 22462741
TI  - Genome and exome sequencing in the clinic: unbiased genomic approaches with a
      high diagnostic yield.
AB  - For the reasons discussed here, we think whole-genome- or exome-based approaches
      are currently most suited for diagnostic implementation in genetically
      heterogeneous diseases, initially to complement and later to replace Sanger
      sequencing, qPCR and genomic microarrays. Patients do need to be counseled for
      the possibility of receiving medically relevant information not related to the
      disease under investigation, but this chance can be minimized by a focused data
      analysis process. Establishing the pathogenicity of individual genetic variants
      remains a daunting task, requiring novel bioinformatic tools and high-throughput
      functional approaches, but at least we can now be more sure that we have not
      missed relevant genetic variation.

PMID- 22462743
TI  - Genetic polymorphisms and retention rate of antiepileptic drugs.

PMID- 22462744
TI  - Golden Helix Pharmacogenomics Days: educational activities on pharmacogenomics
      and personalized medicine.
AB  - The Golden Helix Pharmacogenomics Days are high-profile international educational
      scientific meetings discussing pharmacogenomics and personalized medicine. Here,
      we provide an overview of the scientific lectures and the topics discussed during
      the 4th Golden Helix Pharmacogenomics Day, held in Cagliari, Italy, on 7 October
      2011, and the 5th Golden Helix Pharmacogenomics Day, that was held in Msida,
      Malta, on 3 December 2011. The scientific programs of both events included
      scientific and company lectures on pharmacogenomics, bioinformatics and
      personalized medicine by local and international speakers from Europe and the
      USA.

PMID- 22462745
TI  - Company profile: Sequenom, Inc.
AB  - There is broad acceptance in both the research and clinical communities that the
      age of personalized medicine is rapidly approaching. Numerous examples of
      biomarkers (and tests based on those biomarkers) have been shown to be relevant
      to clinically important phenotypes. Sequenom, Inc. is at the forefront of this
      molecular medicine revolution. The company provides genetic analysis
      instrumentation and reagents to the clinical and research communities. These
      products are being used for clinical validation of relevant biomarkers as well as
      for development of diagnostic tests based on those biomarkers.

PMID- 22462746
TI  - CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese,
      Malay and Indian subjects.
AB  - AIM, MATERIALS & METHODS: We investigated the functional significance of
      CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on
      clopidogrel treatment and the prevalence of functionally significant
      polymorphisms among 300 Chinese, Malays and Asian Indians. RESULTS: Both CYP2C19
      loss-of-function alleles (*2 or *3) were associated with higher platelet
      reactivity while the CYP2C19 gain-of-function allele (*17) had lower platelet
      reactivity. For PON1, the median PRI was not significantly different between the
      QQ, QR and RR groups. The allele frequencies of CYP2C19*2, CYP2C19*3 and
      CYP2C19*17 were 0.280, 0.065 and 0.010 (rare) for Chinese, 0.310, 0.050 and 0.025
      for Malays, and 0.375, 0.010 (rare) and 0.165 for Indians, respectively.
      CONCLUSION: Our data suggest that genotyping studies to investigate clopidogrel
      response should include CYP2C19*2 and *3 but not *17 polymorphisms in Chinese,
      and CYP2C19*2 and *17 polymorphisms but not *3 in Indians. All three
      polymorphisms should preferably be genotyped in Malays.

PMID- 22462747
TI  - Identification of six novel P450 oxidoreductase missense variants in Ashkenazi
      and Moroccan Jewish populations.
AB  - BACKGROUND: The enzyme NADPH-P450 oxidoreductase (POR) is the main electron donor
      to all microsomal CYPs. The possible contribution of common POR variants to inter
      and intra-individual variability in drug metabolism is of great pharmacogenetic
      interest. AIM: To search for POR polymorphic alleles and estimate their
      frequencies in a Jewish population. MATERIALS & METHODS: We analyzed the POR gene
      in 301 Ashkenazi and Moroccan Jews. RESULTS: A total of 30 POR SNPs were
      identified, nine in the noncoding regions and 21 in the protein-coding regions
      (ten synonymous, 11 missense). Six of these missense variants are previously
      undescribed (S102P, V164M, V191M, D344N, E398A and D648N). CONCLUSION: The data
      collected in this study on missense POR SNPs, interpreted in light of the
      crystallographic structure of human POR, indicate that some POR missense variants
      may be potential biomarkers for future POR pharmacogenetic screening.

PMID- 22462749
TI  - Potential of adaptive clinical trial designs in pharmacogenetic research.
AB  - Adaptive trial designs can be beneficial in pharmacogenetic research when prior
      uncertainty exists regarding the exact role and clinical relevance of genetic
      variability in drug response. This type of design enables us to learn about the
      effect of the genetic variability on drug response and to immediately use this
      information for the remainder of the study. For different types of adaptive trial
      designs, we discuss when and how the designs are suitable for pharmacogenetic
      research: adaptation of randomization, adaptation of patient enrollment and
      adaptive enrichment. To illustrate the potential benefits of an adaptive design
      over a fixed design, we simulated an adaptive trial based on the results of the
      IPASS trial. With a simple model we show that for this example an adaptive
      enrichment design would have led to a smaller trial, with less EGF receptor
      mutation-negative patients unnecessarily exposed to the drug, without
      compromising the alpha level or reducing power.

PMID- 22462748
TI  - Worldwide variation in human drug-metabolism enzyme genes CYP2B6 and UGT2B7:
      implications for HIV/AIDS treatment.
AB  - AIM: Hepatic enzymes, CYP2B6 and UGT2B7 play a major role in the metabolism of
      the widely used antiretroviral drugs efavirenz, nevirapine and zidovudine. In the
      present study, we provide a view of UGT2B7 haplotype structure, and quantify the
      genetic diversity and differentiation at both CYP2B6 and UGT2B7 genes on a
      worldwide scale. MATERIALS & METHODS: We genotyped one intronic and three
      promoter SNPs, and together with three nonsynonymous SNPs, inferred UGT2B7
      alleles in north American (n = 326), west African (n = 133) and Papua New Guinean
      (n = 142) populations. We also included genotype data for five CYP2B6 and six
      UGT2B7 SNPs from an additional 12 worldwide populations (n = 629) analyzed in the
      1000 Genomes Project. RESULTS: We observed significant differences in certain SNP
      and allele frequencies of CYP2B6 and UGT2B7 among worldwide populations.
      Diversity values were higher for UGT2B7 than for CYP2B6, although there was more
      diversity between populations for CYP2B6. For both genes, most of the genetic
      variation was observed among individuals within populations, with the Papua New
      Guinean population showing the highest pairwise differentiation values for
      CYP2B6, and the Asian and European populations showing higher pairwise
      differentiation values for UGT2B7. CONCLUSION: These new genetic distinctions
      provide additional insights for investigating differences in antiretroviral
      pharmacokinetics and therapy outcomes among ethnically and geographically diverse
      populations.

PMID- 22462751
TI  - Genetics of ischemic stroke, stroke-related risk factors, stroke precursors and
      treatments.
AB  - Stroke remains a leading cause of death worldwide and the first cause of
      disability in the western world. Ischemic stroke (IS) accounts for almost 80% of
      the total cases of strokes and is a complex and multifactorial disease caused by
      the combination of vascular risk factors, environment and genetic factors.
      Investigations of the genetics of atherosclerosis and IS has greatly enhanced our
      knowledge of this complex multifactorial disease. In this article we sought to
      review common single-gene disorders relevant to IS, summarize candidate gene and
      genome-wide studies aimed at discovering genetic stroke risk factors and
      subclinical phenotypes, and to briefly discuss pharmacogenetics related to stroke
      treatments. Genetics of IS is, in fact, one of the most promising research
      frontiers and genetic testing may be helpful for novel drug discoveries as well
      as for appropriate drug and dose selection for treatment of patients with
      cerebrovascular disease.

PMID- 22462750
TI  - Individualized risk for statin-induced myopathy: current knowledge, emerging
      challenges and potential solutions.
AB  - Skeletal muscle toxicity is the primary adverse effect of statins. In this
      review, we summarize current knowledge regarding the genetic and nongenetic
      determinants of risk for statin induced myopathy. Many genetic factors were
      initially identified through candidate gene association studies limited to
      pharmacokinetic (PK) targets. Through genome-wide association studies, it has
      become clear that SLCO1B1 is among the strongest PK predictors of myopathy risk.
      Genome-wide association studies have also expanded our understanding of
      pharmacodynamic candidate genes, including RYR2. It is anticipated that deep
      resequencing efforts will define new loci with rare variants that also
      contribute, and sophisticated computational approaches will be needed to
      characterize gene-gene and gene-environment interactions. Beyond environment,
      race is a critical covariate, and its influence is only partly explained by
      geographic differences in the frequency of known pharmacodynamic and PK variants.
      As such, admixture analyses will be essential for a full understanding of statin
      induced myopathy.

PMID- 22462752
TI  - Association of ABCB1 polymorphisms with erlotinib pharmacokinetics and toxicity
      in Japanese patients with non-small-cell lung cancer.
AB  - AIMS: We analyzed the association of ABCB1 polymorphisms with erlotinib-induced
      toxicity and the pharmacokinetics in patients with non-small-cell lung cancer.
      MATERIALS & METHODS: After erlotinib 150 mg was administered to 50 patients,
      ABCB1 polymorphisms were analyzed via either TaqMan((r)) assays or direct
      nucleotide sequencing. Plasma concentrations were measured by HPLC. RESULTS: The
      trough concentration at steady state in patients with the ABCB1 1236TT-2677TT
      3435TT genotype was higher compared with others groups (p = 0.021) and patients
      carrying this genotype had a higher risk of developing higher grade 2 toxicity (p
      = 0.012). CONCLUSION: The present study suggested that the ABCB1 1236TT-2677TT
      3435TT genotype was associated with higher plasma concentration and the risk of
      developing higher toxicity in patients treated with erlotinib.

PMID- 22462754
TI  - Expression profiles of regulatory and helper T-cell-associated genes in nasal
      polyposis.
AB  - BACKGROUND: Nasal polyposis (NP) is a Th2-skewed inflammatory disorder, but it is
      unclear what role regulatory T cells (T-reg) play in disease pathology. We
      investigated the expression profiles of T-reg and T-helper-cell-associated genes
      and their response to glucocorticosteroid (GC) treatment in Chinese patients with
      NP. METHODS: Biopsies were obtained from 29 non-treated NP patients for
      comparison with inferior turbinates collected from healthy controls. In 13
      patients, NP samples were collected both before and after short-term oral GC
      treatment. Levels of mRNA for T-cell markers were determined by microarray and
      quantitative PCR. Cellular infiltrates were assessed by histo- and
      immunohistochemistry. RESULTS: FOXP3(+) T-reg were increased in GC-naive NP, and
      numbers were negatively correlated with eosinophil infiltration. Helios staining
      was not detected, suggesting that FOXP3(+) cells in NP are not thymus-derived T
      reg. Compared with controls, mRNA levels corresponding to T-reg genes were
      significantly increased in NP (FOXP3, TGFB1, IL10, SMAD3, IL2RA, and JAK3), but
      transcription factors associated with Th2 (GATA3) or Th17 responses (RORc) were
      significantly reduced. FOXP3 mRNA levels positively correlated with other T-reg
      cell markers. Microarray analysis showed that most Th2-related markers (e.g.,
      Eotaxin-1, CCL13, and CCL18) were upregulated in GC-naive NP vs controls. GC
      therapy significantly suppressed eosinophilic inflammation in NP, but did not
      significantly alter the expression levels of T-reg/Th2-associated genes.
      CONCLUSIONS: Upregulation of FOXP3(+) -inducible T-reg cells and downregulation
      of Th2 and Th17 markers in NP indicate a regulatory response occurring at a site
      of persistent mucosal inflammation. However, immune regulation fails to control
      the underlying tissue pathology. Expression of T-reg/Th2 markers after GC
      treatment was unaltered, suggesting that T-cell-driving NP inflammatory mediators
      are GC resistant.

PMID- 22462755
TI  - Melatonin attenuates hypochlorous acid-mediated heme destruction, free iron
      release, and protein aggregation in hemoglobin.
AB  - In inflammatory diseases, where hypochlorous acid (HOCl) is elevated, iron
      homeostasis is disturbed, resulting in accumulation of free iron. Free iron is
      toxic by virtue of its ability to generate free radicals through the Fenton
      reaction. HOCl is generated by myeloperoxidase, (MPO) using chloride and hydrogen
      peroxide as substrates. Recent studies demonstrate that HOCl binds to the heme
      moiety of hemoglobin (Hb), which generates a transient ferric species whose
      formation and decay kinetics indicate it participates in protein aggregation,
      heme destruction, and free iron release. Here, we show that melatonin prevents
      HOCl-mediated Hb heme destruction and protein aggregation, using a combination of
      UV-vis spectrophotometry, ferrozine colorimetric assay, and in-gel heme staining.
      We also show that melatonin treatment prevents HOCl-mediated loss of red blood
      cell (RBC) viability, indicating biologic relevance of this finding. The
      mechanism by which melatonin prevents HOCl-mediated Hb heme destruction is by
      direct scavenging of HOCl and/or through the destabilization of the higher Hb
      oxidative states intermediates, ferryl porphyrin radical cation Hb-Fe(IV)=O(+pi*)
      and Hb-Fe(IV)=O, which are formed through the reaction of HOCl with Hb. Our work
      establishes a direct mechanistic link between melatonin and its protective effect
      in chronic inflammatory diseases. Collectively, in addition to acting as an
      antioxidant and as a MPO inhibitor, melatonin can also exert its protective
      effect by inhibiting HOCl-mediated heme destruction of hemoproteins and
      subsequent free iron release.

PMID- 22462756
TI  - Bidirectional association between depression and sexual dysfunction: a systematic
      review and meta-analysis.
AB  - INTRODUCTION: Depression is frequently associated with sexual dysfunction in both
      men and women. AIM: To examine whether depression predicts sexual dysfunction
      and, conversely, whether sexual dysfunction predicts depression. METHOD: A
      systematic review and meta-analysis was conducted. PubMed and EMBASE biomedical
      answers electronic databases were searched for relevant studies up to November
      2011. Reference lists of relevant articles were hand-searched and expert opinions
      were sought. Studies identified for inclusion had to be prospective cohort
      studies in adult populations that reported an association between depression and
      sexual dysfunction variables. MAIN OUTCOME MEASURES: Odds ratios (ORs),
      prioritized where available, or relative risks (RRs) were pooled across studies
      using random-effects meta-analysis models. RESULTS: Eight citations included for
      review yielded six studies on depression and risk of sexual dysfunction in 3,285
      participants followed for 2-9 years, and six studies on sexual dysfunction and
      risk of depression in 11,171 participants followed for 1-10 years. Depression
      increased the risk of sexual dysfunction in pooled unadjusted (RR/OR 1.52 with
      95% confidence intervals [1.02, 2.26]) and adjusted (RR/OR 1.71 [1.05, 2.78])
      meta-analyses but not in the partially adjusted model (RR/OR 1.41 [0.90, 2.23]).
      There was significant heterogeneity between studies, but after removal of a
      single outlying study was diminished and the pooled partially adjusted, RR/OR
      increased to 1.69 (1.15, 2.47). Sexual dysfunction increased the odds of
      depression in the pooled unadjusted (OR 2.30 [1.74, 3.03]), adjusted (OR 3.12
      [1.66, 5.85]), and partially adjusted (OR 2.71 [1.93, 3.79]) meta-analyses;
      heterogeneity was significant only in the adjusted model. Meta-regression
      analyses did not detect significant sources of heterogeneity in either
      examination. CONCLUSIONS: Clinicians should be aware of a bidirectional
      association between depression and sexual dysfunction. Patients reporting sexual
      dysfunction should be routinely screened for depression, whereas patients
      presenting with symptoms of depression should be routinely assessed for sexual
      dysfunction.

PMID- 22462757
TI  - Home mechanical ventilation in children is feasible in developing countries.
AB  - BACKGROUND: The results of many national surveys on pediatric home mechanical
      ventilation (HMV) in developed countries have been presented elsewhere, but data
      from developing countries with low national incomes are scarce. METHODS: Twenty
      nine pediatric patients, treated in the Mother and Child Institute of Serbia, who
      had been receiving long-term ventilatory support at home, were surveyed. The
      major criterion for initiating HMV was hypercapnia, diagnosed by blood gas
      analysis, performed in the morning, after awakening. Other criteria were either
      symptoms of hypoventilation during the night associated with an apnea index of
      >5, or apnoea-hypopnoea index of >15, or nocturnal hypoxemia, defined as an
      oxygen saturation rate of <90% for >5% of total sleep time. RESULTS: The mean age
      at initiation of HMV was 9.3 years (range 0.5-17.8 years). Patients waited for
      HMV initiation either in hospital or at home; the mean period was 6.3 months
      (range 1-18 months). The subjects received HMV for a mean of 25.06 months (range
      3-119 months). There was a significant difference in the duration of HMV for
      different underlying diseases (P= 0.046), and mechanical malfunction was strongly
      dependent on the duration of HMV (P= 0.011). Eleven patients underwent invasive
      HMV via a tracheostomy, and 18 others received non-invasive ventilation, via
      nasal and full-face masks. CONCLUSION: HMV is feasible in developing countries.
      Valuable reimbursement policies as well as an organized and functional network
      are essential for its implementation, as a standard of care in leading national
      pediatric hospitals.

PMID- 22462758
TI  - Cell aggregation in thawed haematopoietic stem cell products visualised using
      micro-flow imaging.

PMID- 22462760
TI  - Gestational diabetes and pregnancy outcomes--a systematic review of the World
      Health Organization (WHO) and the International Association of Diabetes in
      Pregnancy Study Groups (IADPSG) diagnostic criteria.
AB  - BACKGROUND: Two criteria based on a 2 h 75 g OGTT are being used for the
      diagnosis of gestational diabetes (GDM), those recommended over the years by the
      World Health Organization (WHO), and those recently recommended by the
      International Association for Diabetes in Pregnancy Study Group (IADPSG), the
      latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to
      systematically review the evidence for the associations between GDM (according to
      these criteria) and adverse outcomes. METHODS: We searched relevant studies in
      MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR,
      EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of
      GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and
      perinatal outcomes in untreated women. Only studies with universal application of
      a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence
      intervals (CI) were obtained for each study. We combined study results using a
      random-effects model. Inconsistency across studies was defined by an
      inconsistency index (I2) > 50%. RESULTS: Data were extracted from eight studies,
      totaling 44,829 women. Greater risk of adverse outcomes was observed for both
      diagnostic criteria. When using the WHO criteria, consistent associations were
      seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for
      gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR
      = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p
      < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data
      were available for the IADPSG criteria, and associations were inconsistent across
      studies (I2 >= 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p =
      0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for
      preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding
      either the HAPO or the EBDG studies minimally altered these associations, but the
      RRs seen for the IADPSG criteria were reduced after excluding HAPO. CONCLUSIONS:
      The WHO and the IADPSG criteria for GDM identified women at a small increased
      risk for adverse pregnancy outcomes. Associations were of similar magnitude for
      both criteria. However, high inconsistency was seen for those with the IADPSG
      criteria. Full evaluation of the latter in settings other than HAPO requires
      additional studies.

PMID- 22462761
TI  - EC145: a novel targeted agent for adenocarcinoma of the lung.
AB  - INTRODUCTION: EC145 is a folate receptor (FR)-targeted vinca alkaloid conjugate
      currently under development as an anticancer agent. The FR is overexpressed on a
      number of major malignancies including adenocarcinoma of the lung and ovarian
      cancer. A companion diagnostic radiopharmaceutical, EC20, allows for non-invasive
      determination of the presence of functionally active FR. AREAS COVERED: This
      review will discuss the rationale for the FR as a target for anticancer agents,
      the pharmacology of EC145 and the preclinical and clinical results for EC145 and
      related compounds. In addition, it will discuss the utility of a companion
      imaging diagnostic, EC20, for the selection of patients who might benefit from
      EC145. EXPERT OPINION: EC145 is a first in class, novel agent with a unique
      target. The companion diagnostic, EC20 may allow for enrichment of the patient
      population, and therefore accelerate development of the drug. The drug has
      demonstrated benefit in preliminary reports of trials in ovarian cancer. If
      similar benefit is demonstrated in lung cancer, the drug is likely to have
      significant use in lung cancer and other malignancies with overexpression of FRs.

PMID- 22462759
TI  - Leveraging "raw materials" as building blocks and bioactive signals in
      regenerative medicine.
AB  - Components found within the extracellular matrix (ECM) have emerged as an
      essential subset of biomaterials for tissue engineering scaffolds. Collagen,
      glycosaminoglycans, bioceramics, and ECM-based matrices are the main categories
      of "raw materials" used in a wide variety of tissue engineering strategies. The
      advantages of raw materials include their inherent ability to create a
      microenvironment that contains physical, chemical, and mechanical cues similar to
      native tissue, which prove unmatched by synthetic biomaterials alone. Moreover,
      these raw materials provide a head start in the regeneration of tissues by
      providing building blocks to be bioresorbed and incorporated into the tissue as
      opposed to being biodegraded into waste products and removed. This article
      reviews the strategies and applications of employing raw materials as components
      of tissue engineering constructs. Utilizing raw materials holds the potential to
      provide both a scaffold and a signal, perhaps even without the addition of
      exogenous growth factors or cytokines. Raw materials contain endogenous proteins
      that may also help to improve the translational success of tissue engineering
      solutions to progress from laboratory bench to clinical therapies. Traditionally,
      the tissue engineering triad has included cells, signals, and materials. Whether
      raw materials represent their own new paradigm or are categorized as a bridge
      between signals and materials, it is clear that they have emerged as a leading
      strategy in regenerative medicine. The common use of raw materials in commercial
      products as well as their growing presence in the research community speak to
      their potential. However, there has heretofore not been a coordinated or
      organized effort to classify these approaches, and as such we recommend that the
      use of raw materials be introduced into the collective consciousness of our field
      as a recognized classification of regenerative medicine strategies.

PMID- 22462762
TI  - Categorization of 77 dystrophin exons into 5 groups by a decision tree using
      indexes of splicing regulatory factors as decision markers.
AB  - BACKGROUND: Duchenne muscular dystrophy, a fatal muscle-wasting disease, is
      characterized by dystrophin deficiency caused by mutations in the dystrophin
      gene. Skipping of a target dystrophin exon during splicing with antisense
      oligonucleotides is attracting much attention as the most plausible way to
      express dystrophin in DMD. Antisense oligonucleotides have been designed against
      splicing regulatory sequences such as splicing enhancer sequences of target
      exons. Recently, we reported that a chemical kinase inhibitor specifically
      enhances the skipping of mutated dystrophin exon 31, indicating the existence of
      exon-specific splicing regulatory systems. However, the basis for such individual
      regulatory systems is largely unknown. Here, we categorized the dystrophin exons
      in terms of their splicing regulatory factors. RESULTS: Using a computer-based
      machine learning system, we first constructed a decision tree separating 77
      authentic from 14 known cryptic exons using 25 indexes of splicing regulatory
      factors as decision markers. We evaluated the classification accuracy of a novel
      cryptic exon (exon 11a) identified in this study. However, the tree mislabeled
      exon 11a as a true exon. Therefore, we re-constructed the decision tree to
      separate all 15 cryptic exons. The revised decision tree categorized the 77
      authentic exons into five groups. Furthermore, all nine disease-associated novel
      exons were successfully categorized as exons, validating the decision tree. One
      group, consisting of 30 exons, was characterized by a high density of exonic
      splicing enhancer sequences. This suggests that AOs targeting splicing enhancer
      sequences would efficiently induce skipping of exons belonging to this group.
      CONCLUSIONS: The decision tree categorized the 77 authentic exons into five
      groups. Our classification may help to establish the strategy for exon skipping
      therapy for Duchenne muscular dystrophy.

PMID- 22462763
TI  - Modulation of epileptiform EEG discharges in juvenile myoclonic epilepsy: an
      investigation of reflex epileptic traits.
AB  - PURPOSE:   Previous studies have suggested that cognitive tasks modulate (provoke
      or inhibit) the epileptiform electroencephalography (EEG) discharges (EDs) in
      patients with juvenile myoclonic epilepsy (JME). Their inhibitory effect was
      found to be especially frequent (64-90%). These studies arbitrarily defined
      modulation as a >100% increase or >50% decrease of the EDs compared with
      baseline, which may not sufficiently distinguish from spontaneous fluctuations.
      The aim of our study was to assess the modulation of EDs and the precipitation of
      myoclonic seizures by cognitive tasks and by conventional provocation methods,
      taking into account also the spontaneous fluctuation of EDs. METHOD:   Sixty
      patients with JME underwent video-EEG recordings including 50-min baseline,
      sleep, hyperventilation, intermittent photic stimulation (IPS), and cognitive
      tasks. To account for spontaneous fluctuations of the EDs we divided the baseline
      period into 5-min epochs and calculated the 95% confidence interval for the
      baseline EDs in each patient. Modulation was assumed when the number of EDs
      during any 5-min test period was outside the 95% confidence interval. KEY
      FINDINGS:   Using the arbitrary method, our results were similar to previous
      publications: Cognitive tasks seemed to inhibit the EDs in 94% of the patients,
      and to provoke them in 22%. However, when the spontaneous fluctuations were
      accounted for, inhibition was found in only 29% of the patients and provocation
      in 18%. A nonspecific effect of any cognitive task seemed to account for the
      observed significant inhibition in two-thirds of the cases, but was observed in
      only one of the patients with significant provocation. Photoparoxysmal response
      was observed in 23% of the patients. When accounting for the spontaneous
      occurrence of EDs, IPS had provocative effect in 10% of the patients.
      Hyperventilation and sleep had provocative effect on EDs to an extent similar to
      the cognitive tasks (hyperventilation: 22%; sleep: 18%). The conventional
      provocation methods tended to be more efficient in patients who were not seizure
      free. Myoclonia were recorded most often during the cognitive tasks (10
      patients). SIGNIFICANCE:   Spontaneous fluctuations of EDs account for most of
      the previously described inhibitory effect of the cognitive tasks. The
      provocative effect of the cognitive tasks is task-specific, whereas the
      inhibitory effect seems to be related to cognitive activation in general.

PMID- 22462764
TI  - Tracing solid waste leachate in groundwater using delta13 C from dissolved
      inorganic carbon.
AB  - Tracers can be used to monitor emissions of leachate from landfills in order to
      detect hydrological pathways and to evaluate environmental pollution. We
      investigated the stable carbon isotope ratio (delta(13)C-Sigma CO (2)) in
      dissolved inorganic carbon and tritium ((3)H) in water, in addition to the
      tracers of pollution commonly found in relatively high concentrations in
      leachate, such as chloride (Cl), organic matter (COD), nitrogen (total and NH(4)
      N), iron (Fe), electrical conductivity (EC) and pH. The sampling was performed at
      seven landfills in the south-eastern part of Norway during a period of 5 years.
      The objective was to evaluate the potential for tracing leachate in the
      environment with emphasis on groundwater pollution. By measuring the delta(13)C
      Sigma CO (2) in leachates, groundwaters and surface waters, the influence of
      leachate can be identified. The value of delta(13)C-Sigma CO (2) varied from-5.5
      to 25.9 0/00 in leachate, from-25.4 to 14.7 0/00 in groundwater and from-19.7 to
      13.1 0/00 in creeks. A comparison of the carbon isotope ratio with COD, EC and
      the concentrations of total and NH (4)-N, Cl and Fe showed that delta(13)C-Sigma
      CO (2) is a good tracer for leachate due to higher sensitivity compared to other
      parameters. The mean concentrations of all the studied parameters were higher in
      the leachate samples; however, only the carbon isotope ratio showed significant
      differences between all the groups with strong and middle pollution and samples
      with low pollution, showing that it can be used as a convenient tracer for
      leachate in groundwater and surface water. The carbon isotope ratio showed strong
      correlation between nitrogen, EC and bicarbonate, but not with pH. Tritium was
      only sporadically found in measureable concentrations and is not considered as a
      suitable tracer at the sampled locations.

PMID- 22462765
TI  - Content validity of visual analog scales to assess symptom severity of acute
      angioedema attacks in adults with hereditary angioedema: an interview study.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare, debilitating, potentially life
      threatening condition characterized by recurrent acute attacks of edema of the
      skin, face/upper airway, and gastrointestinal and urogenital tracts. During a
      laryngeal attack, people with HAE may be at risk of suffocation, while other
      attacks are often associated with intense pain, disfigurement, disability, and/or
      vomiting. The intensity of some symptoms is known only to the person experiencing
      them. Thus, interview studies are needed to explore such experience and patient
      reported outcome measures (PROMs) are required for systematic assessment of
      symptoms in the clinical setting and in clinical trials of treatments for acute
      HAE attacks. OBJECTIVE: The aim of this interview study was to assess the content
      validity and suitability of four visual analog scale (VAS) instruments for use in
      clinical studies. The VAS instruments were designed to assess symptoms at
      abdominal, oro-facial-pharyngeal-laryngeal, peripheral, and urogenital attack
      locations. This is the first known study to report qualitative data about the
      patient's experience of the rare disorder, HAE. METHODS: Semi-structured
      exploratory and cognitive debriefing interviews were conducted with 27 adults
      with a confirmed clinical/laboratory diagnosis of HAE (baseline plasma level of
      functional plasma protein C1 esterase inhibitor [C1INH] <50% of normal without
      evidence for acquired angioedema). There were 17 participants from the US and 10
      from Italy, with mean age 42.5 (SD 14.5) years, range 18-72 years, mean HAE
      duration 21.3 (SD 14.1) years, range 1-45 years, 67% female, and 44% VAS-naive.
      Experience of acute angioedema attacks was first explored, noting spontaneous
      mentions by participants of HAE symptomatology. Cognitive debriefing of the VAS
      instruments was undertaken to assess the suitability, comprehensibility, and
      relevance of the VAS items. Asymptomatic participants completed the VAS
      instruments relevant to their angioedema experience, reporting as if they were
      experiencing an acute angioedema attack at the time. Interviews were conducted in
      the clinic setting in the US and Italy over an 8-month period. RESULTS:
      Participants mentioned spontaneously almost all aspects of acute angioedema
      attacks covered by the four VAS instruments, thus providing strong support for
      inclusion of nearly all VAS items, with no important symptoms missing.
      Predominant symptoms found to be associated with acute angioedema attacks were
      edema and pain, and there was evidence of varying degrees of disruption to
      everyday activities supporting the inclusion of an overall severity item
      reflecting the disabling effects of HAE symptoms. VAS item wording was understood
      by participants. CONCLUSION: This interview study explored and reported the
      patient experience of HAE attacks. It demonstrated the content validity of the
      four anatomical location HAE VAS instruments and their suitability for use in
      clinical trials of recombinant human C1INH (rhC1INH) treatment for ascertaining
      trial participants' assessments of the severity of acute angioedema symptoms.

PMID- 22462766
TI  - Changes in sense of coherence in old age - a 5-year follow-up of the Umea 85+
      study.
AB  - OBJECTIVE: This study aims to describe the changes in sense of coherence (SOC)
      over time and relate these changes to negative life events among very old people.
      DESIGN: Prospective and longitudinal study. SUBJECTS: 190 old women and men
      participated, of whom 56 could be included in the 5-year follow-up. METHODS: The
      mean SOC score from the first and second data collection were compared using a
      paired sample t-test. The relationship between the index of negative life events
      and the changes on SOC score between the two data collections was investigate
      using linear regression. MAIN OUTCOME MEASURES: Antonovsky's SOC scale and an
      index of negative life events including severe physical and mental diseases,
      various losses as losses of spouses, cognitive and functional ability. RESULT:
      For the whole group of subjects (n = 56), the SOC scores was higher (70.1 vs.
      73.7, p = 0.029) at the second point measure. The most common negative life
      events at follow-up were loss of independence in activities in daily living and
      decrease in cognitive function. A significant correlation between the index of
      negative life events and changes in SOC over 5 years was found (p = 0.025). The
      more negative life events, the more decrease in SOC. CONCLUSION: We concluded
      that there is a risk of decreased SOC and thereby quality of life when negative
      life events accumulate among very old people. Nursing interventions might play an
      important role for maintaining and perhaps strengthening SOC among old people
      exposed to negative life events.

PMID- 22462767
TI  - Out-of-Plane Interactions in Parallel-Planar Copper(II) Dimers.  The Structure
      and Magnetic Properties of Dobromobis(2-methylpyridine)copper(II).

PMID- 22462768
TI  - Emerging decontaminants.

PMID- 22462769
TI  - Effects of isopropanol on collagen fibrils in new parchment.
AB  - BACKGROUND: Isopropanol is widely used by conservators to relax the creases and
      folds of parchment artefacts. At present, little is known of the possible side
      effects of the chemical on parchments main structural component- collagen. This
      study uses X-ray Diffraction to investigate the effects of a range of isopropanol
      concentrations on the dimensions of the nanostructure of the collagen component
      of new parchment. RESULTS: It is found in this study that the packing features of
      the collagen molecules within the collagen fibril are altered by exposure to
      isopropanol. The results suggest that this chemical treatment can induce a loss
      of structural water from the collagen within parchment and thus a rearrangement
      of intermolecular bonding. This study also finds that the effects of isopropanol
      treatment are permanent to parchment artefacts and cannot be reversed with
      rehydration using deionised water. CONCLUSIONS: This study has shown that
      isopropanol induces permanent changes to the packing features of collagen within
      parchment artefacts and has provided scientific evidence that its use to remove
      creases and folds on parchment artefacts will cause structural change that may
      contribute to long-term deterioration of parchment artefacts. This work provides
      valuable information that informs conservation practitioners regarding the use of
      isopropanol on parchment artefacts.

PMID- 22462770
TI  - Operational research to inform a sub-national surveillance intervention for
      malaria elimination in Solomon Islands.
AB  - BACKGROUND: Successful reduction of malaria transmission to very low levels has
      made Isabel Province, Solomon Islands, a target for early elimination by 2014.
      High malaria transmission in neighbouring provinces and the potential for local
      asymptomatic infections to cause malaria resurgence highlights the need for sub
      national tailoring of surveillance interventions. This study contributes to a
      situational analysis of malaria in Isabel Province to inform an appropriate
      surveillance intervention. METHODS: A mixed method study was carried out in
      Isabel Province in late 2009 and early 2010. The quantitative component was a
      population-based prevalence survey of 8,554 people from 129 villages, which were
      selected using a spatially stratified sampling approach to achieve uniform
      geographical coverage of populated areas. Diagnosis was initially based on Giemsa
      stained blood slides followed by molecular analysis using polymerase chain
      reaction (PCR). Local perceptions and practices related to management of fever
      and treatment-seeking that would impact a surveillance intervention were also
      explored using qualitative research methods. RESULTS: Approximately 33%
      (8,554/26,221) of the population of Isabel Province participated in the survey.
      Only one subject was found to be infected with Plasmodium falciparum (Pf) (96
      parasites/MUL) using Giemsa-stained blood films, giving a prevalence of 0.01%.
      PCR analysis detected a further 13 cases, giving an estimated malaria prevalence
      of 0.51%. There was a wide geographical distribution of infected subjects. None
      reported having travelled outside Isabel Province in the previous three months
      suggesting low-level indigenous malaria transmission. The qualitative findings
      provide warning signs that the current community vigilance approach to
      surveillance will not be sufficient to achieve elimination. In addition, fever
      severity is being used by individuals as an indicator for malaria and a trigger
      for timely treatment-seeking and case reporting. In light of the finding of a low
      prevalence of parasitaemia, the current surveillance system may not be able to
      detect and prevent malaria resurgence. CONCLUSION: An adaption to the malERA
      surveillance framework is proposed and recommendations made for a tailored
      provincial-level surveillance intervention, which will be essential to achieve
      elimination, and to maintain this status while the rest of the country catches
      up.

PMID- 22462771
TI  - A novel calcium aluminate-melatonin scaffold enhances bone regeneration within a
      calvarial defect.
AB  - Over 500,000 bone graft or bio-implant procedures are performed annually in the
      United States. It has been reported that osseous autograft procurement may result
      in donor site complications and bio-implant allografts have been associated with
      disease transmission. Ceramic scaffolds are only osteoconductive, limiting their
      clinical use. The objective of this study was to create a bone filler substitute
      with regenerating properties similar to natural bone. Therefore, melatonin and
      platelet-rich plasma (PRP) were utilized for their known osteoinductive
      properties. It was hypothesized that melatonin and/or PRP would enhance the
      osteoinductive and osteoconductive properties of calcium aluminate (CA) scaffolds
      to promote bone regeneration in a model of calvarial defects. The
      biocompatibility of CA and CA-Mel scaffolds was tested in vitro and in vivo. Data
      show that CA-Mel scaffolds, in comparison with CA scaffolds, enhanced the
      adhesion, viability, and proliferation of normal human osteoblasts cells but not
      that of NIH3T3 fibroblasts. Data also showed that human adult mesenchymal stem
      cells grown on CA or CA-Mel scaffolds showed a time-dependent induction into
      osteoblasts over 14days revealed through scanning electron microscopy and by
      alkaline phosphatase analyses. Implantation of CA-Mel scaffolds into critical
      size calvarial defects in female, ovariectomized rats showed that the CA-Mel
      scaffolds were biocompatible, allowed for tissue infiltration, and showed
      evidence of scaffold biodegradation by 3 and 6months. Bone regeneration, assessed
      using fluorochrome labeling at 3 and 6months, was greatest in animals implanted
      with the CA-Mel scaffold. Overall, results from this study show that CA-Mel
      scaffolds were osteoconductive and osteoinductive.

PMID- 22462772
TI  - Synthesis and anti-HIV activity of lupane and olean-18-ene derivatives. Absolute
      configuration of 19,20-epoxylupanes by VCD.
AB  - Lupane triterpenoids 2 and 5-12 and oleanene derivatives 13 and 14 were prepared
      from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV
      activity, and some structure-activity relationships were outlined. The 20-(S)
      absolute configuration of epoxylupenone (8) was assessed by comparison of the
      observed and DFT-calculated vibrational circular dichroism spectra. The
      CompareVOA algorithm was employed to support the C-20 configuration assignment.
      The 20,29 double bond in lupenone (2) and 3-epilupeol (15) was stereoselectively
      epoxidized to produce 20-(S)-8 and 20-(S)-16, respectively, an assignment in
      agreement with their X-ray diffraction structures.

PMID- 22462774
TI  - The impact and burden of chronic pain in the workplace: a qualitative systematic
      review.
AB  - BACKGROUND: Chronic pain (CP) poses a diverse and substantial burden for
      employees, employers, and society. The deleterious consequences of CP in the
      workplace are frequently underestimated. OBJECTIVE: To estimate the burden of CP
      in the European workplace. METHODS: A systematic review following PRISMA
      statement guidelines was conducted to identify studies reporting work-related
      outcomes for people with CP. EMBASE, MEDLINE, EconLit, and Cochrane Library
      databases were searched up to 18th August 2010. RESULTS: We identified 91
      observational studies. Few were specifically designed to investigate the
      association between CP, productivity, and employment. The focus for this review
      was studies clearly reporting outcomes relating to the burden of CP on employment
      status (n = 37), sickness absence (absenteeism, n = 47), and loss of productivity
      because of reduced ability at work (presenteeism, n = 8). CONCLUSION: The body of
      evidence identified from the systematic review indicates that CP has a
      substantial negative impact on work-related outcomes, supporting the importance
      of interventions to reduce the burden of CP. Well-designed prospective studies
      specifically assessing the direct consequences of CP on employment are needed to
      confirm these findings.

PMID- 22462773
TI  - Myeloperoxidase-derived chlorinating species induce protein carbamylation through
      decomposition of thiocyanate and urea: novel pathways generating dysfunctional
      high-density lipoprotein.
AB  - AIMS: Protein carbamylation through cyanate is considered as playing a causal
      role in promoting cardiovascular disease. We recently observed that the phagocyte
      protein myeloperoxidase (MPO) specifically induces high-density lipoprotein (HDL)
      carbamylation, rather than chlorination, in human atherosclerotic lesions,
      raising the possibility that MPO-derived chlorinating species are involved in
      cyanate formation. RESULTS: Here, we show that MPO-derived chlorinating species
      rapidly decompose the plasma components thiocyanate (SCN) and urea, thereby
      promoting (lipo)protein carbamylation. Strikingly, the presence of physiologic
      concentrations of SCN completely prevented MPO-induced 3-chlorotyrosine formation
      in HDL. SCN scavenged a 2.5-fold molar excess of hypochlorous acid, promoting HDL
      carbamylation, but not chlorination. Cyanate significantly impaired (i) HDL's
      ability to activate lecithin-cholesterol acyltransferase; (ii) the activity of
      paraoxonase, a major HDL-associated anti-inflammatory enzyme; and (iii) the
      antioxidative activity of HDL. INNOVATION: Here, we report that MPO-derived
      chlorinating species preferentially induce protein carbamylation-rather than
      chlorination-in the presence of physiologically relevant SCN concentrations. The
      carbamylation of HDL results in the loss of its anti-inflammatory and
      antioxidative activities. CONCLUSION: MPO-mediated decomposition of SCN and/or
      urea might be a relevant mechanism for generating dysfunctional HDL in human
      disease.

PMID- 22462775
TI  - Site-selective bromination of vancomycin.
AB  - We report the site-selective bromination of vancomycin to produce, with
      substantial efficiency, previously unknown monobromovancomycins, a
      dibromovancomycin, and a tribromovancomycin. We document the inherent reactivity
      of native vancomycin toward N-bromophthalimide. We then demonstrate significant
      rate acceleration and perturbation of the inherent product distribution in the
      presence of a rationally designed peptide-based promoter. Alternative site
      selectivity is observed as a function of solvent and replacement of the peptide
      with guanidine.

PMID- 22462777
TI  - Charge trapping in bright and dark states of coupled PbS quantum dot films.
AB  - Analysis of photoluminescence (PL) from chemically treated lead sulfide (PbS)
      quantum dot (QD) films versus temperature reveals the effects of QD size and
      ligand binding on the motion of carriers between bright and dark trap states. For
      strongly coupled QDs, the PL exhibits temperature-dependent quenching and
      shifting consistent with charges residing in a shallow exponential tail of quasi
      localized states below the band gap. The depth of the tail varies from 15 to 40
      meV, similar to or smaller than exponential band tail widths measured for
      polycrystalline Si. The trap state distribution can be manipulated with QD size
      and surface treatment, and its characterization should provide a clearer picture
      of charge separation and percolation in disordered QD films than what currently
      exists.

PMID- 22462776
TI  - AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal
      peritoneal carcinomatosis model.
AB  - BACKGROUND: Angiogenesis plays an important role in tumor growth and metastasis,
      therefore antiangiogenic therapy was widely investigated as a promising approach
      for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been
      shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus
      (AAV) vectors have been intensively studied due to their wide tropisms,
      nonpathogenicity, and long-term transgene expression in vivo. The objective of
      this work was to evaluate the ability of AAV-mediated human PEDF (hPEDF) as a
      potent tumor suppressor and a potential candidate for cancer gene therapy.
      METHODS: Recombinant AAV2 encoding hPEDF (rAAV2-hPEDF) was constructed and
      produced, and then was assigned for in vitro and in vivo experiments. Conditioned
      medium from cells infected with rAAV2-hPEDF was used for cell proliferation and
      tube formation tests of human umbilical vein endothelial cells (HUVECs).
      Subsequently, colorectal peritoneal carcinomatosis (CRPC) mouse model was
      established and treated with rAAV2-hPEDF. Therapeutic efficacy of rAAV2-hPEDF
      were investigated, including tumor growth and metastasis, survival time,
      microvessel density (MVD) and apoptosis index of tumor tissues, and hPEDF levels
      in serum and ascites. RESULTS: rAAV2-hPEDF was successfully constructed, and
      transmission electron microscope (TEM) showed that rAAV2-hPEDF particles were non
      enveloped icosahedral shape with a diameter of approximately 20 nm. rAAV2-hPEDF
      infected cells expressed hPEDF protein, and the conditioned medium from infected
      cells inhibited proliferation and tube-formation of HUVECs in vitro. Furthermore,
      in CRPC mouse model, rAAV2-hPEDF significantly suppressed tumor growth and
      metastasis, and prolonged survival time of treated mice. Immunofluorescence
      studies indicated that rAAV2-hPEDF could inhibit angiogenesis and induce
      apoptosis in tumor tissues. Besides, hPEDF levels in serum and ascites of rAAV2
      hPEDF-treated mice were significant higher than those in rAAV2-null or normal
      saline (NS) groups. CONCLUSIONS: Thus, our results suggest that rAAV2-hPEDF may
      be a potential candidate as an antiangiogenic therapy agent.

PMID- 22462778
TI  - Screening of CO(2) laser (10.6 MUm) parameters for prevention of enamel erosion.
AB  - OBJECTIVE: The aim of this study was to screen CO(2) laser (10.6 MUm) parameters
      to increase enamel resistance to a continuous-flow erosive challenge. BACKGROUND
      DATA: A new clinical CO(2) laser providing pulses of hundreds of microseconds, a
      range known to increase tooth acid-resistance, has been introduced in the market.
      METHODS: Different laser parameters were tested in 12 groups (n=20) with varying
      fluences from 0.1 to 0.9 J/cm(2), pulse durations from 80 to 400 MUs and
      repetition rates from 180 to 700 Hz. Non-lased samples (n=30) served as controls.
      All samples were eroded by exposure to hydrochloric acid (pH 2.6) under
      continuous acid flow (60 MUL/min). Calcium and phosphate release into acid was
      monitored colorimetrically at 30 sec intervals up to 5 min and at 1 min intervals
      up to a total erosion time of 15 min. Scanning electron microscopic (SEM)
      analysis was performed in lased samples (n=3). Data were statistically analysed
      by one-way ANOVA (p<0.05) and Dunnett's post-hoc tests. RESULTS: Calcium and
      phosphate release were significantly reduced by a maximum of 20% over time in
      samples irradiated with 0.4 J/cm(2) (200MUs) at 450 Hz. Short-time reduction of
      calcium loss (<=1.5 min) could be also achieved by irradiation with 0.7 J/cm(2)
      (300MUs) at 200 and 300 Hz. Both parameters revealed surface modification.
      CONCLUSIONS: A set of CO(2) laser parameters was found that could significantly
      reduce enamel mineral loss (20%) under in vitro erosive conditions. However, as
      all parameters also caused surface cracking, they are not recommended for
      clinical use.

PMID- 22462779
TI  - Spatial scale and divergent patterns of variation in adapted traits in the ocean.
AB  - The geography of adaptive genetic variation is crucial to species conservation
      yet poorly understood in marine systems. We analyse the spatial scale of genetic
      variation in traits that broadly display adaptation throughout the range of a
      highly dispersive marine species. We conducted common garden experiments on the
      Atlantic silverside, Menidia menidia, from 39 locations along its 3000 km range
      thereby mapping genetic variation for growth rate, vertebral number and sex
      determination. Each trait displayed unique clinal patterns, with significant
      differences (adaptive or not) occurring over very small distances. Breakpoints in
      the cline differed among traits, corresponding only partially with presumed eco
      geographical boundaries. Because clinal patterns are unique to each selected
      character, neutral genes or those coding for a single character cannot serve as
      proxies for the genetic structure as a whole. Conservation plans designed to
      protect essential genetic subunits of a species will need to account for such
      complex spatial structures.

PMID- 22462780
TI  - Differential signaling transduction networks for clinical robustness.

PMID- 22462781
TI  - How will increasing our knowledge of the head and neck cancer cells' secretome
      benefit head and neck squamous cell carcinoma patients?

PMID- 22462783
TI  - The changing face of screening and drug discovery.
AB  - Screening Asia 2011, Singapore, 22-23 November 2011. The meeting covered
      traditional topics such as high-content screening and assay development, as well
      as more contemporary, emergent areas involving novel screening platforms and
      technologies, strategies to deal with biosimilars and biologics, and natural
      product diversity. Notably, many talks challenged established screening practices
      and the use of 'combichem' small-molecule libraries. Instead, speakers offered an
      alternate view of compound library design and screening strategies that could
      better mimic the target and cell status found in the relevant disease state.

PMID- 22462784
TI  - Optimal selection of 2D reversed-phase-reversed-phase HPLC separation techniques
      in bottom-up proteomics.
AB  - Recent developments in bottom-up proteomics have supplanted the use of gel-based
      approaches in favor of multidimensional chromatographic separations of peptide
      mixtures followed by mass spectrometry analysis. This trend is driven by the
      desire to eliminate labor-intensive in-gel digestion procedures and increase
      proteome coverage through better recovery of proteolytic fragments. Introduction
      of reversed-phase-reversed-phase 2D separation techniques is one of the major
      improvements that have made this possible. In this article, we review recent
      developments in 2D HPLC and highlight variations in reversed-phase HPLC
      separation selectivity that allow for superior peak capacity in peptide
      fractionation.

PMID- 22462785
TI  - High-pH reversed-phase chromatography with fraction concatenation for 2D
      proteomic analysis.
AB  - Orthogonal high-resolution separations are critical for attaining improved
      analytical dynamic range and protein coverage in proteomic measurements. High-pH
      reversed-phase liquid chromatography (RPLC), followed by fraction concatenation,
      affords better peptide analysis than conventional strong cation-exchange
      chromatography applied for 2D proteomic analysis. For example, concatenated high
      pH RPLC increased identification of peptides (by 1.8-fold) and proteins (by 1.6
      fold) in shotgun proteomics analyses of a digested human protein sample.
      Additional advantages of high-pH RPLC with fraction concatenation include
      improved protein sequence coverage, simplified sample processing and reduced
      sample losses, making this an attractive alternative to strong cation-exchange
      chromatography in conjunction with second-dimension low-pH RPLC for 2D proteomics
      analyses.

PMID- 22462787
TI  - Biomarkers for cervical cancer screening: the role of p16(INK4a) to highlight
      transforming HPV infections.
AB  - Biomarkers indicating the initiation of neoplastic transformation processes in
      human papillomavirus (HPV)-infected epithelial cells are moving into the focus of
      cancer prevention research, particularly for anogenital cancer, including cancer
      of the uterine cervix. Based on the in-depth understanding of the molecular
      events leading to neoplastic transformation of HPV-infected human cells, the
      cyclin-dependent kinase inhibitor p16(INK4a) turned out to be substantially
      overexpressed in virtually all HPV-transformed cells. This finding opened novel
      avenues in diagnostic histopathology to substantially improve the diagnostic
      accuracy of cervical cancer and its precursor lesions. Furthermore, it provides a
      novel technical platform to substantially improve the accuracy of cytology-based
      cancer early-detection programs. Here, we review the molecular background and the
      current evidence for the clinical utility of the p16(INK4a) biomarker for HPV
      related cancers, and cervical cancer prevention in particular.

PMID- 22462786
TI  - Microscale 2D separation systems for proteomic analysis.
AB  - Microscale 2D separation systems have been implemented in capillaries and
      microfabricated channels. They offer advantages of faster analysis, higher
      separation efficiency and less sample consumption than the conventional methods,
      such as liquid chromatography (LC) in a column and slab gel electrophoresis. In
      this article, we review their recent advancement, focusing on three types of
      platforms, including 2D capillary electrophoresis (CE), CE coupling with
      capillary LC, and microfluidic devices. A variety of CE and LC modes have been
      employed to construct 2D separation systems via sophistically designed
      interfaces. Coupling of different separation modes has also been realized in a
      number of microfluidic devices. These separation systems have been applied for
      the proteomic analysis of various biological samples, ranging from a single cell
      to tumor tissues.

PMID- 22462788
TI  - The proteomic toolbox for studying cerebrospinal fluid.
AB  - Cerebrospinal fluid (CSF) can be considered the most promising biosample for the
      discovery and analysis of biomarkers in neuroscience, an area of great medical
      need. CSF is a body fluid that surrounds the brain and provides a rich pool of
      biochemical markers, both proteomic and metabolomic, that reflect the state of
      neurological processes. Such biomarkers can either serve as diagnostic or
      prognostic biomarkers to improve the characterization of patients and preclinical
      disease models, or can be used to demonstrate drug-related exposure and efficacy.
      Here, we describe the proteomic toolbox for studying CSF from a drug-discovery
      perspective, and the trends and challenges that lie ahead.

PMID- 22462789
TI  - Angiopoietin-like protein 4: health effects, modulating agents and structure
      function relationships.
AB  - Angiopoietin-like protein 4 (ANGPTL4) has been identified as a multifunctional
      signal protein. It is produced by a variety of tissues, and is secreted into the
      bloodstream in glycosylated, oligomerized, native and cleaved isoforms to
      modulate physiological events such as angiogenesis, cell differentiation and the
      crosstalk between liver, brain, adipose and muscle tissue in lipid and glucose
      metabolism. In addition, the expression and isoform appearance of ANGPTL4 are
      modified by the intestinal microbiota. With an eye on an effective strategy to
      improve health using ANGPTL4, we will focus on: health issues associated with
      ANGPTL4 expression, including obesity, Type 2 diabetes, cardiovascular diseases
      and cancer; several modulators of ANGPTL4 of chemical, microbiological, food and
      host origin; and the correlation of the specific ANGPTL4 isoforms with these
      modulators and their health effects.

PMID- 22462790
TI  - Monocyte/macrophage proteomics: recent findings and biomedical applications.
AB  - Macrophages, originating from the migration and differentiation of circulating
      monocytes into virtually all tissues, are extremely flexible and plastic cells
      that play vital homeostatic roles, but also contribute to the pathophysiology of
      many human diseases. For these reasons, they are intensively studied by different
      approaches, recently including proteomics. Macrophage cells can be taken from a
      range of different sources, including blood monocytes and macrophages from
      tissues. Macrophages can also be generated by in vitro culture from blood
      monocytes, and cell lines derived from this lineage can be used. Similarly, many
      different proteomic techniques can be used, ranging from classic approaches based
      on 2D gel electrophoresis to more recent high-throughput gel-free techniques
      essentially based on mass spectrometry. Here, we review the application of such
      techniques to the study of monocytes/macrophages, and summarize some results
      potentially relevant to two paradigmatic conditions - atherosclerosis and
      disorders of iron metabolism.

PMID- 22462791
TI  - Human mesenchymal stromal cell proteomics: contribution for identification of new
      markers and targets for medicine intervention.
AB  - Mesenchymal stem or stromal cells (MSCs) have become of great interest for cell
      based therapy owing to their roles in tissue repair and immune suppression. MSCs
      have the ability to differentiate into specialized tissues, including bone,
      cartilage and muscle, among several others. Furthermore, it has been found that
      MSCs can also serve as cellular factories that secrete mediators to stimulate in
      situ regeneration of injured tissues. Proteomics has contributed significantly to
      the identification of new proteins to improve cellular characterization of MSCs,
      to identify new targets for therapeutic intervention and to elucidate important
      pathways utilized by MSCs to differentiate into distinct tissues. As proteomics
      technology advances, several studies can be revisited and analyzed in depth,
      employing state-of-the-art approaches, helping to uncover the cellular mechanisms
      utilized by MSCs to exert their regenerative functionalities. In this article, we
      will review the progress made so far and discuss further opportunities for
      proteomics to contribute to the clinical applications of MSCs.

PMID- 22462793
TI  - Blood cleansing cells in head kidney and spleen in Buenos Aires tetra,
      Hyphessobrycon anisitsi (Eigenmann), (Characidae: Teleostei).
AB  - The general structure and cell types in kidney and spleen in Buenos Aires tetra,
      Hyphessobrycon anisitsi, family Characidae, are described. The capability and
      capacity of these organs to clean foreign ferritin from the blood stream are
      analysed and compared. Head kidney was mainly composed of neutrophils,
      macrophages, lymphocytes and other white blood cells, whereas unmatured and
      matured red blood cells were few in number. Spleen often contained much red pulp,
      that is mainly matured red blood cells between splenic cords, often with some
      macrophages and neutrophils in the latter. Occasionally, this pulp contained
      large volumes of unmatured red blood cells, particularly in the periphery of the
      spleen. The splenic white pulp consisted of ellipsoids composed of an inner
      endothelial layer covered by a thick sheet of white blood cells, which in the
      periphery consisted mainly of macrophages. Erythrocytes occupied nearly the
      entire splenic volume in some specimens, whereas up to half of this volume was
      filled by ellipsoid macrophages, neutrophils, lymphocytes and other white blood
      cells in other specimens. The macrophages and sinusoidal endothelial cells in
      kidney and spleen from ferritin-injected specimens were tightly packed by yellow
      brown granules or Prussian blue precipitations, in tissue treated with Mallory
      stain or acid ferrocyanide, respectively, suggesting a large uptake of foreign
      ferritin. In the present tetra large amounts of white blood cells are developed
      in head kidney, where macrophages and sinusoidal endothelial cells play important
      roles in the cleansing of scavenger and foreign molecules and particles from the
      blood stream. The spleen seems primarily to be a site for iron recycling and
      production and storage of red blood cells. Sometimes, however, it was rich in
      macrophages, neutrophils, lymphocytes and other white blood cells, suggesting
      functions like blood cleansing and non-specific and specific defence in such
      specimens.

PMID- 22462795
TI  - The etiological relationship between anxiety sensitivity, sexual distress, and
      female sexual dysfunction is partly genetically moderated.
AB  - INTRODUCTION: Presence of sexual distress is diagnostic requirement for female
      sexual dysfunction (FSD). However, previous correlational research indicates that
      sexual distress in women may be related to general anxiety per se rather than
      being an outcome of FSD. AIM: In this exploratory study, we test, for the first
      time, whether the correlation between anxiety sensitivity, sexual distress, and
      FSD can be explained by shared genetic and nongenetic factors using multivariate
      twin modeling. METHODS: Questionnaire data were available on a representative
      final sample of 930 Caucasian British female twin individuals (119 monozygotic
      twin pairs, 67 dizygotic twin pairs, and 558 single twins; aged 18-85 years).
      Validated scales assessed anxiety sensitivity, sexual distress, and FSD and
      included the Female Sexual Function Index, the Female Sexual Distress Scale, and
      the Anxiety Sensitivity Index. MAIN OUTCOME MEASURES: Questionnaire responses
      were subject to trivariate heritability analyses to assess common genetic and
      environmental influences underlying specific trait variance and the covariance
      between the phenotypes. RESULTS: Heritability for FSD was 28%, 48% for anxiety
      sensitivity, and 44% for sexual distress. The phenotypic associations among
      anxiety sensitivity, sexual distress, and FSD were all significant. Trivariate
      analysis indicated that additive genetic factors accounted for approximately 75%
      of the covariance between anxiety sensitivity and FSD 35% of the covariance
      between anxiety sensitivity and sexual distress, and 11% between sexual distress
      and FSD. CONCLUSIONS: The association between anxiety sensitivity and FSD has a
      common genetic component. There is a weaker genetic link between anxiety
      sensitivity and sexual distress and between sexual distress and FSD. These data,
      while silent on direction of causality, suggest a role for pleiotropic genetic
      factors influencing anxiety sensitivity and FSD. They also highlight a need to
      refine the inclusion of distress in classifications of disorders of female sexual
      functioning.

PMID- 22462794
TI  - Using cadence to study free-living ambulatory behaviour.
AB  - The health benefits of a physically active lifestyle across a person's lifespan
      have been established. If there is any single physical activity behaviour that we
      should measure well and promote effectively, it is ambulatory activity and, more
      specifically, walking. Since public health physical activity guidelines include
      statements related to intensity of activity, it follows that we need to measure
      and promote free-living patterns of ambulatory activity that are congruent with
      this intent. The purpose of this review article is to present and summarize the
      potential for using cadence (steps/minute) to represent such behavioural patterns
      of ambulatory activity in free-living. Cadence is one of the spatio-temporal
      parameters of gait or walking speed. It is typically assessed using short
      distance walks in clinical research and practice, but free-living cadence can be
      captured with a number of commercially available accelerometers that possess time
      stamping technology. This presents a unique opportunity to use the same metric to
      communicate both ambulatory performance (assessed under testing conditions) and
      behaviour (assessed in the real world). Ranges for normal walking cadence
      assessed under laboratory conditions are 96-138 steps/minute for women and 81-135
      steps/minute for men across their lifespan. The correlation between mean cadence
      and intensity (assessed with indirect calorimetry and expressed as metabolic
      equivalents [METs]) based on five treadmill/overground walking studies, is r =
      0.93 and 100 steps/minute is considered to be a reasonable heuristic value
      indicative of walking at least at absolutely-defined moderate intensity (i.e.
      minimally, 3 METs) in adults. The weighted mean cadence derived from eight
      studies that have observed pedestrian cadence under natural conditions was 115.2
      steps/minute, demonstrating that achieving 100 steps/minute is realistic in
      specific settings that occur in real life. However, accelerometer data collected
      in a large, representative sample suggest that self-selected walking at a cadence
      equivalent to >=100 steps/minute is a rare occurrence in free-living adults.
      Specifically, the National Health and Nutrition Examination Survey (NHANES) data
      show that US adults spent ?4.8 hours/day in non-movement (i.e. zero cadence)
      during wearing time, ?8.7 hours at 1-59 steps/minute, ?16 minutes/day at cadences
      of 60-79 steps/minute, ?8 minutes at 80-99 steps/minute, ?5 minutes at 100-119
      steps/minute, and ?2 minutes at 120+ steps/minute. Cadence appears to be
      sensitive to change with intervention, and capitalizing on the natural tempo of
      music is an obvious means of targeting cadence. Cadence could potentially be used
      effectively in epidemiological study, intervention and behavioural research, dose
      response studies, determinants studies and in prescription and practice. It is
      easily interpretable by researchers, clinicians, programme staff and the lay
      public, and therefore offers the potential to bridge science, practice and real
      life.

PMID- 22462796
TI  - Clinical and imaging overview of functional adrenal neoplasms.
AB  - Adrenal adenoma, adrenocortical carcinoma, pheochromocytoma and neuroblastoma are
      four discrete adrenal neoplasms that have the potential for functional activity.
      Functional adrenal neoplasms can secrete cortisol, aldosterone, sex hormones or
      catecholamines. These heterogeneous groups of tumors show varied biological
      behavior and clinical outcomes. These neoplasms are encountered with increasing
      clinical frequency as a result of an expansion in the volume of medical imaging
      carried out. The clinical presentation, including prognosis and treatment
      options, and the imaging features of these neoplasms are discussed. The key
      radiological observations of each of these neoplasms are shown using
      multimodality images. Familiarity with the clinical and imaging features of these
      neoplasms improves diagnosis, and facilitates appropriate clinical decision
      making and patient management.

PMID- 22462798
TI  - Ethanol isotope method (EIM) for uncovering illegal wine.
AB  - Isotopic methods have proven to be a powerful analytical tool for the
      determination of origin and authenticity of wine. In addition, measuring the
      stable isotope ratio provides useful information for the detection of many
      illegal practices in the production of wine. The determinations of the stable
      isotope composition of compounds are based on measuring the relative ratios using
      isotope ratio mass spectrometry. This article describes a new isotopic method for
      measuring the deltaD value of non-exchangeable hydrogen stable isotopes in
      ethanol for investigating adulteration practices in wine making. With this new
      method, we are able to determine the addition of water and sugar in wine with
      higher accuracy, repeatability and reliability.

PMID- 22462797
TI  - New STLV-3 strains and a divergent SIVmus strain identified in non-human primate
      bushmeat in Gabon.
AB  - BACKGROUND: Human retroviral infections such as Human Immunodeficiency Virus
      (HIV) or Human T-cell Lymphotropic Virus (HTLV) are the result of simian zoonotic
      transmissions through handling and butchering of Non-Human Primates (NHP) or by
      close contact with pet animals. Recent studies on retroviral infections in NHP
      bushmeat allowed for the identification of numerous Simian Immunodeficiency
      Viruses (SIV) and Simian T-cell Lymphotropic Viruses (STLV) to which humans are
      exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter
      interface remain scarce. We conducted a pilot study on 63 blood and/or tissues
      samples derived from NHP bushmeat seized by the competent authorities in
      different locations across the country. RESULTS: SIV and STLV were detected by
      antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an
      HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples
      cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1
      infections in five of the seven species tested. STLV-3 infections, including a
      new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3
      infections were observed in red-capped mangabeys (C.torquatus). We confirmed SIV
      infections by PCR and sequence analyses in mandrills, red-capped mangabeys and
      showed that mustached monkeys in Gabon are infected with a new SIV strain basal
      to the SIVgsn/mus/mon lineage that did not fall into the previously described
      SIVmus lineages reported from the corresponding species in Cameroon. The same
      monkey (sub)species can thus be carrier of, at least, three distinct SIVs.
      Overall, the minimal prevalence observed for both STLV and SIV natural infections
      were 26.9% and 11.1% respectively. CONCLUSIONS: Overall, these data, obtained
      from a restricted sampling, highlight the need for further studies on simian
      retroviruses in sub-Saharan Africa to better understand their evolutionary
      history and to document SIV strains to which humans are exposed. We also show
      that within one species, a high genetic diversity may exist for SIVs and STLVs
      and observe a high genetic diversity in the SIVgsn/mon/mus lineage, ancestor of
      HIV-1/SIVcpz/SIVgor.

PMID- 22462799
TI  - The most cited works in epilepsy: Trends in the "Citation Classics".
AB  - The number of times that a published article is cited is one indicator of its
      scientific impact. An article is termed a "Citation Classic" once it has
      accumulated more than 400 citations. Trends in these highly cited works allow
      projection of future directions of high-impact research within a field. Herein,
      we identified 89 articles in the field of epilepsy published in 35 different
      journals that have been cited more than 400 times (citation range 401-3,749). The
      journal that published the greatest number of Citation Classics was Epilepsia (9
      articles with 656 mean citations per article). Laboratory studies constituted the
      fastest growing area of highly cited epilepsy research, whereas clinical studies
      showed a bimodal distribution in representation among Citation Classics. There
      were also considerably fewer epilepsy-specific Citation Classics compared to
      other disciplines. In this study, we find that the Citation Classics of epilepsy
      comprise a heterogeneous group of articles and that changes in the trends of
      these highly cited works represent the evolution of epilepsy research over time.
      The results of this study should inform the academic community and provide a
      guide of essential literature for scientists who are engaged in epilepsy
      research.

PMID- 22462800
TI  - Endocultivation: metabolism during heterotopic osteoinduction in vivo--monitoring
      with fiber optic detection devices.
AB  - Reconstructions of facial bone defects are one of the most challenging aspects in
      surgical treatment of malignant diseases, large facial traumata, or congenital
      anomalies. High-level reconstruction techniques are often associated with an
      elevated morbidity by the harvest of autologous bone grafts from the patient.
      Tissue engineering techniques may help to solve this problem. The aim of this
      study was to monitor metabolic processes during cellular colonization of matrices
      in vivo in an established rat model for endocultivation. After implantation of
      computer-designed hydroxyapatite scaffolds into the latissimus dorsi muscle of
      six rats, 100 MUg bone morphogenetic protein-2 (BMP-2) was injected twice, in
      week 1 and 2, directly into the center of the matrices. The development of pH
      value and oxygen (O2) saturation inside the matrix was followed by fiber optic
      detection technique over 8 weeks and analyzed by variance analyses. Bone density
      measurements were performed by computed tomography as well as histological
      evaluations. Two weeks after implantation, oxygen supply and pH value
      measurements had decreased significantly. In the following weeks both parameters
      increased and stabilized on higher levels. This is the first study reporting a
      reproducible method to follow metabolic processes during heterotopic
      osteoinduction in vivo. It was shown that in the beginning of the study pH value
      and O2 saturation decreased and it took several weeks to regain physiological
      levels. This is an important step to further understand the physiological process
      of bone induction.

PMID- 22462802
TI  - The linkage isomerism of bridging thiocyanate in binuclear complexes.

PMID- 22462801
TI  - Early onset of sexual intercourse is an indicator for hazardous lifestyle and
      problematic life situation.
AB  - BACKGROUND: In public health efforts, knowledge about risk-groups is important
      for creating societal conditions to ensure good health on equal terms. AIM: To
      investigate differences in lifestyle and perceived health among 15-year-old
      teenagers with experience of sexual intercourse (self-defined) and same-aged
      teenagers without experience of sexual intercourse. METHODS: A two-cluster
      questionnaire study among 15-year-old Swedish students (n = 2170) in 2009/10. Chi
      squared test was used to identify differences between three groups: teenagers who
      had not had sexual intercourse; teenagers who had had sexual intercourse at age
      of 14 or younger; and teenagers who had had intercourse at an age of 15. RESULTS:
      Thirty-two per cent (n = 334) of girls and 31% (n = 324) of boys had had sexual
      intercourse. Teenagers with experience of sexual intercourse at 15 years or
      younger used more tobacco, alcohol and illicit drugs than same-aged teenagers
      without intercourse experience did. Furthermore, teenagers with experience of
      intercourse, especially those with a debut at 14 year or younger, had less
      positive school experiences, more involvement in injuries and physical violence,
      were less (girls) and more (boys) physically active, and perceived a poorer
      health than teenagers without intercourse experience. CONCLUSION: Sexual
      intercourse at the age of 15 or younger is an indicator for a hazardous lifestyle
      and problematic life situation.

PMID- 22462804
TI  - Vestibular evoked myogenic potentials in term newborn infants with severe
      hyperbilirubinemia.
AB  - BACKGROUND: The aim of this study was to determine the effects of severe
      hyperbilirubinemia on vestibular evoked myogenic potentials (VEMP). METHODS: A
      prospective study was designed. Seventeen term infants who suffered from severe
      hyperbilirubinemia in the first 5 postnatal days of age were included in the
      study group. The control group consisted of 17 healthy term infants. Audiological
      evaluation was performed, including tympanometry and transient evoked otoacoustic
      emissions, and VEMP tests. RESULTS: All newborns passed audiological evaluation.
      Biphasic waveforms of VEMP were obtained in all of the 34 infants who had been
      tested. Both latencies of p13 and n23 were significantly delayed in the severe
      hyperbilirubinemia group (P < 0.05). CONCLUSION: This pilot is the first study to
      show that severe hyperbilirubinemia causes delay in VEMP latencies. We suggest
      that severe hyperbilirubinemia might affect the vestibular nuclei or the
      integrity of the inferior vestibular nerve and vestibulospinal tract. Further
      studies need to explain the relation between hyperbilirubinemia and the
      vestibular system.

PMID- 22462803
TI  - Pandemic 2009 A(H1N1) infection requiring hospitalization of elderly Spanish
      adults.
AB  - OBJECTIVES: To describe the clinical presentation and prognosis of elderly adults
      hospitalized with pandemic 2009 A(H1N1) influenza infection and to compare these
      data with those of younger patients. DESIGN: Prospective, observational,
      multicenter study. SETTING: Thirteen hospitals in Spain. PARTICIPANTS: Adults
      admitted to the hospital with confirmed pandemic 2009 A(H1N1) influenza
      infection. MEASUREMENTS: Demographic, clinical, laboratory, radiological, and
      outcome variables. RESULTS: Between June 12 and November 10, 2009, 585 adults
      with confirmed 2009 A(H1N1) influenza were hospitalized, of whom 50 (8.5%) were
      aged 65 and older (median age 72, range 65-87). Older adults (>= 65) were more
      likely to have associated comorbidities (88.0% vs 51.2%; P < .001), primarily
      chronic pulmonary diseases (46.0% vs 27.3%; P < .001). Lower respiratory tract
      symptoms and signs such as dyspnea (60.0% vs 45.6%) and wheezing (46.0% vs 27.8%;
      P = .007) were also more common in these elderly adults, although pulmonary
      infiltrates were present in just 14 (28.0%) of the older adults, compared with
      221 (41.3%) of the younger adults (P = .06). Multilobar involvement was less
      frequent in elderly adults with pulmonary infiltrates than younger adults with
      pulmonary infiltrates (21.4% vs 60.0%; P = .05). Rhinorrhea (4.0% vs 21.9%; P =
      .003), myalgias (42.0% vs 59.1%; P = .01), and sore throat (14.0% vs 29.2%; P =
      .02) were more frequent in younger adults. Early antiviral therapy (<48 hours)
      was similar in the two groups (34.0% vs 37.9%; P = .58). Two older adults (4.0%)
      died during hospitalization, compared with 11 (2.1%) younger adults (P = .30).
      CONCLUSION: Elderly adults with 2009 A(H1N1) influenza had fewer viral-like upper
      respiratory symptoms than did younger adults. Pneumonia was more frequent in
      younger adults. No significant differences were observed in hospital mortality.

PMID- 22462806
TI  - Treatment outcome of intravenous artesunate in patients with severe malaria in
      the Netherlands and Belgium.
AB  - BACKGROUND: Intravenous (IV) artesunate is the treatment of choice for severe
      malaria. In Europe, however, no GMP-manufactured product is available and
      treatment data in European travellers are scarce. Fortunately, artesunate became
      available in the Netherlands and Belgium through a named patient programme. This
      is the largest case series of artesunate treated patients with severe malaria in
      Europe. METHODS: Hospitalized patients treated with IV artesunate between
      November 2007 and December 2010 in the Netherlands and Belgium were
      retrospectively evaluated. Patient characteristics, treatment and clinical
      outcome were recorded on a standardized form and mortality, parasite clearance
      times and the occurrence of adverse events were evaluated. RESULTS: Of the 68
      treated patients, including 55 with severe malaria, two patients died (2/55 =
      3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4
      hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4)
      respectively. Artesunate was well tolerated. However, an unusual form of
      haemolytic anaemia was observed in seven patients. The relationship with
      artesunate remains uncertain. CONCLUSIONS: Data from the named patient programme
      demonstrate that IV artesunate is effective and well-tolerated in European
      travellers lacking immunity. However, increased attention needs to be paid to the
      possible development of haemolytic anaemia 2-3 weeks after start of
      treatment.Treatment of IV artesunate should be limited to the period that IV
      treatment is required and should be followed by a full oral course of an
      appropriate anti-malarial drug.

PMID- 22462805
TI  - De novo sequencing and characterization of Picrorhiza kurrooa transcriptome at
      two temperatures showed major transcriptome adjustments.
AB  - BACKGROUND: Picrorhiza kurrooa Royle ex Benth. is an endangered plant species of
      medicinal importance. The medicinal property is attributed to monoterpenoids
      picroside I and II, which are modulated by temperature. The transcriptome
      information of this species is limited with the availability of few hundreds of
      expressed sequence tags (ESTs) in the public databases. In order to gain insight
      into temperature mediated molecular changes, high throughput de novo
      transcriptome sequencing and analyses were carried out at 15  degrees C and 25 
      degrees C, the temperatures known to modulate picrosides content. RESULTS: Using
      paired-end (PE) Illumina sequencing technology, a total of 20,593,412 and
      44,229,272 PE reads were obtained after quality filtering for 15  degrees C and
      25  degrees C, respectively. Available (e.g., De-Bruijn/Eulerian graph) and in
      house developed bioinformatics tools were used for assembly and annotation of
      transcriptome. A total of 74,336 assembled transcript sequences were obtained,
      with an average coverage of 76.6 and average length of 439.5. Guanine-cytosine
      (GC) content was observed to be 44.6%, while the transcriptome exhibited
      abundance of trinucleotide simple sequence repeat (SSR; 45.63%) markers.Large
      scale expression profiling through "read per exon kilobase per million (RPKM)",
      showed changes in several biological processes and metabolic pathways including
      cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs) and those associated
      with picrosides biosynthesis. RPKM data were validated by reverse transcriptase
      polymerase chain reaction using a set of 19 genes, wherein 11 genes behaved in
      accordance with the two expression methods. CONCLUSIONS: Study generated
      transcriptome of P. kurrooa at two different temperatures. Large scale expression
      profiling through RPKM showed major transcriptome changes in response to
      temperature reflecting alterations in major biological processes and metabolic
      pathways, and provided insight of GC content and SSR markers. Analysis also
      identified putative CYPs and UGTs that could help in discovering the hitherto
      unknown genes associated with picrosides biosynthesis.

PMID- 22462809
TI  - DNA surface modified gadolinium phosphate nanoparticles as MRI contrast agents.
AB  - Oligonucleotide modified gadolinium phosphate nanoparticles have been prepared
      and their magnetic resonance relaxivity properties measured. Nanoparticles of
      GdPO4.H2O were synthesized in a water/oil microemulsion using IGEPAL CO-520 as
      surfactant, resulting in 50 to 100 nm particles that are highly dispersible and
      stable in water. Using surface modification chemistry previously established for
      zirconium phosphonate surfaces, the particles are directly modified with 5'
      phosphate terminated oligonucleotides, and the specific interaction of the
      divalent phosphate with Gd(3+) sites at the surface is demonstrated. The ability
      of the modified nanoparticles to act as MRI contrast agents was determined by
      performing MR relaxivity measurements at 14.1 T. Solutions of nanopure water,
      Feridex, and Omniscan (FDA approved contrast agents) in 0.25% agarose were used
      for comparison and control purposes. MRI data confirm that GdPO4.H2O
      nanoparticles have relaxivities (r1, r2) comparable to those of commercially
      available contrast agents. In addition, the data suggest that
      biofunctionalization of the surface of the nanoparticles does not prevent their
      function as MRI contrast agents. 

PMID- 22462808
TI  - Factors associated with difficulty accessing crack cocaine pipes in a Canadian
      setting.
AB  - INTRODUCTION AND AIMS: Crack cocaine pipe sharing is associated with various
      health-related harms, including hepatitis C transmission. Although difficulty
      accessing crack pipes has been found to predict pipe sharing, little is known
      about the factors that limit pipe access in settings where pipes are provided at
      no cost, albeit in limited capacity. Therefore, we investigated crack pipe access
      among people who use drugs in Vancouver, Canada. DESIGN AND METHODS: Data were
      collected through two Canadian prospective cohort studies. Generalised estimating
      equations with logit link for binary outcomes were used to identify factors
      associated with difficulty accessing crack pipes. RESULTS: Among 914 participants
      who reported using crack cocaine, 33% reported difficulty accessing crack pipes.
      In multivariate analyses, factors independently associated with difficulty
      accessing crack pipes included: sex work involvement [adjusted odds ratio (AOR) =
      1.57; 95% confidence interval (CI): 1.03-2.39], having shared a crack pipe (AOR =
      1.69; 95% CI: 1.32-2.16), police presence where one buys/uses drugs (AOR = 1.47;
      95% CI: 1.10-1.95), difficulty accessing services (AOR = 1.74; 95% CI: 1.31-2.32)
      and health problems associated with crack use (AOR = 1.37; 95% CI: 1.04-1.79).
      Reasons given for difficulty accessing pipes included sources being closed
      (48.2%) and no one around selling pipes (18.1%). DISCUSSION AND CONCLUSIONS: A
      substantial proportion of people who smoke crack cocaine report difficulty
      accessing crack pipes in a setting where pipes are available at no cost but in
      limited quantity. These findings indicate the need for enhanced efforts to
      distribute crack pipes and address barriers to pipe access.

PMID- 22462811
TI  - Synthesis and biological activities of topopyrones.
AB  - Structure-activity studies were employed to investigate the stabilization of DNA
      topoisomerases I and II covalent binary complexes by topopyrone analogues. The
      synthesis of five new topopyrone derivatives and study of their ability to
      stabilize DNA-topoisomerase I and DNA-topoisomerase II covalent binary complexes
      are described. The biochemical assays suggest that the orientation of the fused
      1,4-pyrone ring and halogen substituents contribute importantly to the overall
      potency of the topopyrones as topoisomerase poisons.

PMID- 22462810
TI  - JS-K, a glutathione/glutathione S-transferase-activated nitric oxide releasing
      prodrug inhibits androgen receptor and WNT-signaling in prostate cancer cells.
AB  - BACKGROUND: Nitric oxide (NO) and its oxidative reaction products have been
      repeatedly shown to block steroid receptor function via nitrosation of zinc
      finger structures in the DNA-binding domain (DBD). In consequence NO-donors could
      be of special interest for the treatment of deregulated androgen receptor(AR)
      signaling in castration resistant prostate cancer (CRPC). METHODS: Prostate
      cancer (PCa) cells were treated with JS-K, a diazeniumdiolate derivate capable of
      generating large amounts of intracellular NO following activation by glutathione
      S-transferase. Generation of NO was determined indirectly by the detection of
      nitrate in tissue culture medium or by immunodetection of nitrotyrosine in the
      cytoplasm. Effects of JS-K on intracellular AR-levels were determined by western
      blotting. AR-dimerization was analyzed by mammalian two hybrid assay, nuclear
      translocation of the AR was visualized in PCa cells transfected with a green
      fluorescent AR-Eos fusion protein using fluorescence microscopy. Modulation of AR
      and WNT-signalling by JS-K was investigated using reporter gene assays. Tumor
      cell proliferation following JS-K treatment was measured by MTT-Assay. RESULTS:
      The NO-releasing compound JS-K was shown to inhibit AR-mediated reporter gene
      activity in 22Rv1 CRPC cells. Inhibition of AR signaling was neither due to an
      inhibition of nuclear import nor to a reduction in AR-dimerization. In contrast
      to previously tested NO-donors, JS-K was able to reduce the intracellular
      concentration of functional AR. This could be attributed to the generation of
      extremely high intracellular levels of the free radical NO as demonstrated
      indirectly by high levels of nitrotyrosine in JS-K treated cells. Moreover, JS-K
      diminished WNT-signaling in AR-positive 22Rv1 cells. In line with these
      observations, castration resistant 22Rv1 cells were found to be more susceptible
      to the growth inhibitory effects of JS-K than the androgen dependent LNCaP which
      do not exhibit an active WNT-signaling pathway. CONCLUSIONS: Our results suggest
      that small molecules able to inhibit WNT- and AR-signaling via NO-release
      represent a promising platform for the development of new compounds for the
      treatment of CRPC.

PMID- 22462813
TI  - Accounting for dispersal and biotic interactions to disentangle the drivers of
      species distributions and their abundances.
AB  - Although abiotic factors, together with dispersal and biotic interactions, are
      often suggested to explain the distribution of species and their abundances,
      species distribution models usually focus on abiotic factors only. We propose an
      integrative framework linking ecological theory, empirical data and statistical
      models to understand the distribution of species and their abundances together
      with the underlying community assembly dynamics. We illustrate our approach with
      21 plant species in the French Alps. We show that a spatially nested modelling
      framework significantly improves the model's performance and that the spatial
      variations of species presence-absence and abundances are predominantly explained
      by different factors. We also show that incorporating abiotic, dispersal and
      biotic factors into the same model bring new insights to our understanding of
      community assembly. This approach, at the crossroads between community ecology
      and biogeography, is a promising avenue for a better understanding of species co
      existence and biodiversity distribution.

PMID- 22462814
TI  - Changes to financial incentives in English dentistry 2006-2009: a qualitative
      study.
AB  - OBJECTIVES: To explore the views of NHS dentists in England regarding reforms,
      which changed their incentive and payment structure. METHODS: Semi-structured
      interviews with 35 dentists, digitally recorded, transcribed verbatim and
      analysed using a constant comparative method. RESULTS: Dentists reported changing
      their behaviour in response to incentives in ways that were likely to have
      adverse impacts on patients. There was also a loss of trust in NHS paymasters, as
      well as a loss of faith in the ability to provide high quality care in NHS
      dentistry. CONCLUSIONS: Responses suggest that many dentists were quick to change
      behaviour following the introduction of a revised contractual structure in 2006.
      The coalition government in the UK has stated its intention to introduce a new
      NHS dental contract. Our data suggest that part of the process of changing
      behaviours, norms and attitudes will require the rebuilding of trust in the NHS
      amongst NHS dentists, as opposed to merely redesigning incentive structures,
      though the two are related.

PMID- 22462815
TI  - International prevalence of adolescent non-suicidal self-injury and deliberate
      self-harm.
AB  - BACKGROUND: The behaviours of non-suicidal self-injury (NSSI) and deliberate self
      harm (DSH) are prevalent among adolescents, and an increase of rates in recent
      years has been postulated. There is a lack of studies to support this
      postulation, and comparing prevalence across studies and nations is complicated
      due to substantial differences in the methodology and nomenclature of existing
      research. METHODS: We conducted a systematic review of current (2005 - 2011)
      empirical studies reporting on the prevalence of NSSI and DSH in adolescent
      samples across the globe. RESULTS: Fifty-two studies fulfilling the inclusion
      criteria were obtained for analysis. No statistically significant differences
      were found between NSSI (18.0% SD = 7.3) and DSH (16.1% SD = 11.6) studies.
      Assessment using single item questions led to lower prevalence rates than
      assessment with specific behaviour checklists. Mean prevalence rates have not
      increased in the past five years, suggesting stabilization. CONCLUSION: NSSI and
      DSH have a comparable prevalence in studies with adolescents from different
      countries. The field would benefit from adopting a common approach to assessment
      to aide cross-cultural study and comparisons.

PMID- 22462816
TI  - Cohort mortality study of roofing granule mine and mill workers. Part II.
      Epidemiologic analysis, 1945-2004.
AB  - The mortality of 2650 employees (93.4% males) in the mine and mill production of
      roofing granules at four plants was examined between 1945 and 2004. Hypotheses
      focused on diseases associated with exposure to silica: nonmalignant respiratory
      disease, lung cancer, and nonmalignant renal disease. Study eligibility required
      >= 1 year of employment by 2000. Work history and vital status were followed
      through 2004 with < 1% lost to follow-up. Industrial hygiene sampling data (1871
      sampling measurements over a 32-year period) and professional judgment were used
      to construct 15 respirable crystalline silica exposure categories. A category was
      assigned to all plant-, department-, and time-dependent standard job titles.
      Cumulative respirable crystalline silica exposure (mg/m(3)-years) was calculated
      as the sum of the product of time spent and the average exposure for each plant-,
      department-, job-, and calendar-year combination. The cohort geometric mean was
      0.17 mg/m(3)-years (geometric standard deviation 4.01) and differed by plant.
      Expected deaths were calculated using U.S. (entire cohort) and regional (each
      plant) mortality rates. Poisson regression was used for internal comparisons. For
      the entire cohort, 772 deaths (97.4% males) were identified (standardized
      mortality ratio 0.95, 95% CI 0.88-1.02). There were 50 deaths from nonmalignant
      respiratory diseases (1.14, 95% CI 0.85-1.51). Lagging exposure 15 years among
      the male cohort, the relative risks for nonmalignant respiratory disease were
      1.00 (reference), 0.80, 1.94, and 2.03 (p value trend = 0.03) when cumulative
      exposure was categorized < 0.1, 0.1- < 0.5, 0.5- < 1.0, and >= 1.0 mg/m(3)-years,
      respectively. There was a total of 77 lung cancer deaths (1.11, 95% CI 0.88
      1.39). Lagging exposure 15 years, the relative risks for males were 1.00
      (reference), 1.83, 1.83, and 1.05 (p value trend = 0.9). There were 16 deaths
      from nonmalignant renal disease (1.76, 95% CI 1.01-2.86). This exposure-response
      trend was suggestive but imprecise. The study results are consistent with other
      cohorts with similar levels of exposure to respirable crystalline silica.

PMID- 22462818
TI  - Morphometric evaluation of megakaryocytes in bone marrow aspirates of immune
      mediated thrombocytopenic purpura.
AB  - Immune-mediated thrombocytopenic purpura (ITP), one of the common causes of
      thrombocytopenia, is characterized by morphologic alterations in megakaryocytes
      in the bone marrow. Few studies have explored morphometric measurements of
      megakaryocytes in bone marrow trephine biopsies. Quantitative morphometric
      analysis of megakaryocytes in bone marrow aspirate smears is lacking in the
      available literature. This study was aimed at evaluating the morphometric
      alterations in megakaryocytes in cases of ITP on bone marrow aspirate smears vis
      a-vis non-ITP cases. In this study, 35 cases of ITP and 15 non-ITP aspirates were
      included. The bone marrow aspirate smears were reviewed for diagnosis. Computer
      aided image analysis was performed in all aspirate smears for megakaryocytic
      morphometric measurements, including cytoplasmic and nuclear features.
      Appropriate statistical tests were applied for comparison. Megakaryocytes in
      cases of ITP showed a higher nuclear/cytoplasmic ratio (p = 0.021), lower nuclear
      roundness factor (p = 0.04) and lower nuclear contour ratio (p = 0.027). Cellular
      circularity and compactness were significantly different in ITP as compared to
      non-ITP cases, indicating that the megakaryocytes were less round in ITP
      subjects. Discriminant analysis and cross-validation studies found that 65.5% of
      megakaryocytes could be correctly classified as ITP or non-ITP. This study shows
      that significant alterations occur in megakaryocytes in cases of ITP. These
      changes can potentially be utilized in the development of algorithms for computer
      assisted diagnosis of such cases on bone marrow aspirates.

PMID- 22462819
TI  - Trimethylsilyl Esters of Phosphorus Acids. III. Esters of Difluoro-and
      Bis(trifluoromethyl)phosphinous and -thiophosphinous Acids.

PMID- 22462820
TI  - Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor
      resistance and viral replicative capacity.
AB  - BACKGROUND: Mutations in the substrate of HIV-1 protease, especially changes in
      the NC/p1 cleavage site, can directly contribute to protease inhibitor (PI)
      resistance and also compensate for defects in viral replicative capacity (RC) due
      to a drug resistant protease. These NC/p1 changes are known to enhance processing
      of the Gag protein. To investigate the capacity of HIV-1 to modulate Gag cleavage
      and its consequences for PI resistance and RC, we performed a detailed enzymatic
      and virological analysis using a set of PI resistant NC/p1 variants (HXB2431V,
      HXB2436E+437T, HXB2437T and HXB2437V). RESULTS: Here, we demonstrate that single
      NC/p1 mutants, which displayed only a slight increase in PI resistance did not
      show an obvious change in RC. In contrast, the double NC/p1 mutant, which
      displayed a clear increase in processing efficiency and PI resistance,
      demonstrated a clear reduction in RC. Cleavage analysis showed that a
      tridecameric NC/p1 peptide representing the double NC/p1 mutant was cleaved in
      two specific ways instead of one.The observed decrease in RC for the double NC/p1
      mutant (HXB2436E+437T) could (partially) be restored by either reversion of the
      436E change or by acquisition of additional changes in the NC/p1 cleavage site at
      codon 435 or 438 as was revealed during in vitro evolution experiments. These
      changes not only restored RC but also reduced PI resistance levels. Furthermore
      these changes normalized Gag processing efficiency and obstructed the novel
      secondary cleavage site observed for the double NC/p1 mutant. CONCLUSIONS: The
      results of this study clearly demonstrate that HIV-1 can modulate Gag processing
      and thereby PI resistance. Distinct increases in Gag cleavage and PI resistance
      result in a reduced RC that can only be restored by amino acid changes in NC/p1
      which reduce Gag processing to an optimal rate.

PMID- 22462821
TI  - Genetic basis of apnoea of prematurity and caffeine treatment response: role of
      adenosine receptor polymorphisms: genetic basis of apnoea of prematurity.
AB  - AIM: Caffeine treatment reduces the frequency of apnoea of prematurity (AOP) and
      eliminates the need for mechanical ventilation by acting as a nonspecific
      inhibitor of adenosine A1 and adenosine 2A receptors. Patients with AOP have
      demonstrated variant responses to caffeine therapy. We proposed to investigate
      the role of A1 and 2A polymorphisms in the development of AOP and individual
      differences in caffeine response. Secondly, we aimed to determine whether these
      polymorphisms have any effect on bronchopulmonary dysplasia (BPD) development.
      METHODS: Cord blood samples were collected from infants born with gestational
      ages between 24 and 34 weeks. Two groups were defined: patients without apnoea (n
      = 60) and patients with apnoea (n = 55). Patients with apnoea were divided into
      two subgroups: a caffeine-responsive group (n = 30) and an unresponsive group (n
      = 25). Six single-nucleotide polymorphisms were chosen for genotyping. RESULTS:
      Patients with apnoea over 28 weeks of gestational age who responded to the
      caffeine treatment were found to carry the rs16851030 C/C genotype rather than
      the C/T or T/T genotype. Logistic regression analysis showed a significant
      correlation between rs35320474-C/T and T/T genotypes and apnoea and BPD
      development. CONCLUSION: Our results indicate a role for adenosine receptor gene
      polymorphisms in susceptibility to AOP and BPD and in interindividual variability
      to caffeine response.

PMID- 22462822
TI  - Toxicity of synthetic naphthenic acids and mixtures of these to fish liver cells.
AB  - Environmental concerns have been raised over the toxicity of crude naphthenic
      acids (NA) originating from oil exploration activities offshore, oil sands
      exploitation onshore, and use of refined NA as wood preservatives, tire
      additives, and in various other applications. The NA exist in highly complex
      mixtures, so the toxic effects of the individual acids are rarely known. The
      present study investigated the relationships between the chemical structures of a
      range of synthetic alicyclic and aromatic acids and their acute toxicities both
      as single chemicals and as complex mixtures in a primary culture of rainbow trout
      (Oncorhynchus mykiss) hepatocytes. The combined toxicity of multicomponent
      mixtures of these NA was assessed using the concept of concentration addition
      (CA) and independent action (IA) prediction. All of the acids tested were
      moderately toxic, with EC(50) values in the range 108-405 MUM (24-89 mg L(-1))
      and 188-656 MUM (43-148 mg L(-1)) when assessed by effects on metabolic
      inhibition or loss of membrane integrity, respectively. Binary and 6-compound
      mixture of NA caused combined toxicity according to the concept of additivity,
      although slight deviations from additivity were observed at a few mixture
      concentrations. Single NA and mixtures of NA with similar structures to those
      tested herein probably contribute to the toxicity of complex natural mixtures of
      NA. Toxicity tests on three commercial NA mixtures showed that these exhibited
      highly variable toxicities themselves probably reflecting their chemical
      heterogeneity.

PMID- 22462824
TI  - Hydraulic limits preceding mortality in a pinon-juniper woodland under
      experimental drought.
AB  - Drought-related tree mortality occurs globally and may increase in the future,
      but we lack sufficient mechanistic understanding to accurately predict it. Here
      we present the first field assessment of the physiological mechanisms leading to
      mortality in an ecosystem-scale rainfall manipulation of a pinon-juniper (Pinus
      edulis-Juniperus monosperma) woodland. We measured transpiration (E) and modelled
      the transpiration rate initiating hydraulic failure (E(crit) ). We predicted that
      isohydric pinon would experience mortality after prolonged periods of severely
      limited gas exchange as required to avoid hydraulic failure; anisohydric juniper
      would also avoid hydraulic failure, but sustain gas exchange due to its greater
      cavitation resistance. After 1 year of treatment, 67% of droughted mature pinon
      died with concomitant infestation by bark beetles (Ips confusus) and bluestain
      fungus (Ophiostoma spp.); no mortality occurred in juniper or in control pinon.
      As predicted, both species avoided hydraulic failure, but safety margins from
      E(crit) were much smaller in pinon, especially droughted pinon, which also
      experienced chronically low hydraulic conductance. The defining characteristic of
      trees that died was a 7 month period of near-zero gas exchange, versus 2 months
      for surviving pinon. Hydraulic limits to gas exchange, not hydraulic failure per
      se, promoted drought-related mortality in pinon pine.

PMID- 22462825
TI  - Communication: Quantum Zeno-based control mechanism for molecular fragmentation.
AB  - A quantum control mechanism is proposed for molecular fragmentation processes
      within a scenario grounded on the quantum Zeno effect. In particular, we focus on
      the van der Waals Ne-Br(2) complex, which displays two competing dissociation
      channels via vibrational and electronic predissociation. Accordingly, realistic
      three-dimensional wave packet simulations are carried out by using ab initio
      interaction potentials recently obtained to reproduce available experimental
      data. Two numerical models to simulate the repeated measurements are reported and
      analyzed. It is found that the otherwise fast vibrational predissociation is
      slowed down in favor of the slow electronic (double fragmentation)
      predissociation, which is enhanced by several orders of magnitude. Based on these
      theoretical predictions, some hints to experimentalists to confirm their validity
      are also proposed.

PMID- 22462823
TI  - Unravelling the molecular basis for light modulated cellulase gene expression -
      the role of photoreceptors in Neurospora crassa.
AB  - BACKGROUND: Light represents an important environmental cue, which exerts
      considerable influence on the metabolism of fungi. Studies with the
      biotechnological fungal workhorse Trichoderma reesei (Hypocrea jecorina) have
      revealed an interconnection between transcriptional regulation of cellulolytic
      enzymes and the light response. Neurospora crassa has been used as a model
      organism to study light and circadian rhythm biology. We therefore investigated
      whether light also regulates transcriptional regulation of cellulolytic enzymes
      in N. crassa. RESULTS: We show that the N. crassa photoreceptor genes wc-1, wc-2
      and vvd are involved in regulation of cellulase gene expression, indicating that
      this phenomenon is conserved among filamentous fungi. The negative effect of VVD
      on production of cellulolytic enzymes is thereby accomplished by its role in
      photoadaptation and hence its function in White collar complex (WCC) formation.
      In contrast, the induction of vvd expression by the WCC does not seem to be
      crucial in this process. Additionally, we found that WC-1 and WC-2 not only act
      as a complex, but also have individual functions upon growth on cellulose.
      CONCLUSIONS: Genome wide transcriptome analysis of photoreceptor mutants and
      evaluation of results by analysis of mutant strains identified several candidate
      genes likely to play a role in light modulated cellulase gene expression. Genes
      with functions in amino acid metabolism, glycogen metabolism, energy supply and
      protein folding are enriched among genes with decreased expression levels in the
      wc-1 and wc-2 mutants. The ability to properly respond to amino acid starvation,
      i. e. up-regulation of the cross pathway control protein cpc-1, was found to be
      beneficial for cellulase gene expression. Our results further suggest a
      contribution of oxidative depolymerization of cellulose to plant cell wall
      degradation in N. crassa.

PMID- 22462826
TI  - Communication: Revised electron affinity of SF6 from kinetic data.
AB  - Previously determined experimental data for thermal attachment of electrons to
      SF(6) and thermal detachment from SF(6)(-) over the range 590-670 K are
      reevaluated by a third-law analysis. Recent high precision calculations of SF(6)(
      ) harmonic frequences and anharmonicities (for several of the modes) lead to
      considerable changes in modeled vibrational partition functions which then have
      to be accommodated for by a smaller value of the derived adiabatic electron
      affinity EA of SF(6). The previously estimated value of EA = 1.20 (+/-0.05) eV in
      this way is reduced to a value of EA = 1.03 (+/-0.05) eV. In addition, the bond
      dissociation energy E(0,dis) for SF(6)(-) -> SF(5)(-) + F is reduced to E(0,dis)
      = 1.44 (+/-0.05) eV. Finally, the consequences for modeled specific rate
      constants k(det)(E,J) of electron detachment from SF(6)(-) are discussed.

PMID- 22462827
TI  - Communication: Engineered tunable decay rate and controllable dissipative
      dynamics.
AB  - We investigate the steering dissipative dynamics of a two-level system (qubit) by
      means of the modulation of an assisted tunneling degree of freedom which is
      described by a quantum-oscillator spin-boson model. Our results reveal that the
      decoherence rate of the qubit can be significantly suppressed and simultaneously
      its quality factor is enhanced. Moreover, the modulated dynamical susceptibility
      exhibits a multi-peak feature which is indicative of the underlying structure and
      measurable in experiment. Our findings demonstrate that the interplay between the
      combined degrees of freedom and the qubit is crucial for reducing the dissipation
      of qubit and expanding the coherent regime of quantum operation much large. The
      strategy might be used to fight against deterioration of quantum coherence in
      quantum information processing.

PMID- 22462828
TI  - Communication: Time-resolved fluorescence of highly single crystalline molecular
      wires of azobenzene.
AB  - We report the enhanced fluorescence with the remarkably long lifetime (1.17 ns)
      in the first excited state (S(1)) of highly crystalline molecular wires of
      azobenzene at the excitation wavelength of 467 nm for the first time. This
      observation suggests that trans-cis photoisomerization through the rotation or
      inversion mechanism may not be a favorable pathway after excitation to the S(1)
      state in highly single crystalline molecular wires of azobenzene due to the
      hindered motion within densely packed crystal structure. We also measured the
      fluorescence lifetime image of a single crystalline molecular wire of azobenzene,
      indicating that the lifetime was remarkably uniform and that there was only a
      very minor variation within the crystal.

PMID- 22462829
TI  - Vibrational absorption spectra from vibrational coupled cluster damped linear
      response functions calculated using an asymmetric Lanczos algorithm.
AB  - We report the theory and implementation of vibrational coupled cluster (VCC)
      damped response functions. From the imaginary part of the damped VCC response
      function the absorption as function of frequency can be obtained, requiring
      formally the solution of the now complex VCC response equations. The absorption
      spectrum can in this formulation be seen as a matrix function of the
      characteristic VCC Jacobian response matrix. The asymmetric matrix version of the
      Lanczos method is used to generate a tridiagonal representation of the VCC
      response Jacobian. Solving the complex response equations in the relevant Lanczos
      space provides a method for calculating the VCC damped response functions and
      thereby subsequently the absorption spectra. The convergence behaviour of the
      algorithm is discussed theoretically and tested for different levels of
      completeness of the VCC expansion. Comparison is made with results from the
      recently reported [P. Seidler, M. B. Hansen, W. Gyorffy, D. Toffoli, and O.
      Christiansen, J. Chem. Phys. 132, 164105 (2010)] vibrational configuration
      interaction damped response function calculated using a symmetric Lanczos
      algorithm. Calculations of IR spectra of oxazole, cyclopropene, and uracil
      illustrate the usefulness of the new VCC based method.

PMID- 22462830
TI  - Universal state-selective corrections to multi-reference coupled-cluster theories
      with single and double excitations.
AB  - The recently proposed universal state-selective (USS) corrections [K. Kowalski,
      J. Chem. Phys. 134, 194107 (2011)] to approximate multi-reference coupled-cluster
      (MRCC) energies can be commonly applied to any type of MRCC theory based on the
      Jeziorski-Monkhorst [B. Jeziorski and H. J. Monkhorst, Phys. Rev. A 24, 1668
      (1981)] exponential ansatz. In this paper we report on the performance of a
      simple USS correction to the Brillouin-Wigner and Mukherjee's MRCC approaches
      employing single and double excitations (USS-BW-MRCCSD and USS-Mk-MRCCSD). It is
      shown that the USS-BW-MRCCSD correction, which employs the manifold of single and
      double excitations, can be related to a posteriori corrections utilized in
      routine BW-MRCCSD calculations. In several benchmark calculations we compare the
      USS-BW-MRCCSD and USS-Mk-MRCCSD results with the results obtained with the full
      configuration interaction method.

PMID- 22462831
TI  - Ionic force field optimization based on single-ion and ion-pair solvation
      properties: going beyond standard mixing rules.
AB  - Using molecular dynamics (MD) simulations in conjunction with the SPC/E water
      model, we optimize ionic force-field parameters for seven different halide and
      alkali ions, considering a total of eight ion-pairs. Our strategy is based on
      simultaneous optimizing single-ion and ion-pair properties, i.e., we first fix
      ion-water parameters based on single-ion solvation free energies, and in a second
      step determine the cation-anion interaction parameters (traditionally given by
      mixing or combination rules) based on the Kirkwood-Buff theory without
      modification of the ion-water interaction parameters. In doing so, we have
      introduced scaling factors for the cation-anion Lennard-Jones (LJ) interaction
      that quantify deviations from the standard mixing rules. For the rather size
      symmetric salt solutions involving bromide and chloride ions, the standard mixing
      rules work fine. On the other hand, for the iodide and fluoride solutions,
      corresponding to the largest and smallest anion considered in this work, a
      rescaling of the mixing rules was necessary. For iodide, the experimental
      activities suggest more tightly bound ion pairing than given by the standard
      mixing rules, which is achieved in simulations by reducing the scaling factor of
      the cation-anion LJ energy. For fluoride, the situation is different and the
      simulations show too large attraction between fluoride and cations when compared
      with experimental data. For NaF, the situation can be rectified by increasing the
      cation-anion LJ energy. For KF, it proves necessary to increase the effective
      cation-anion Lennard-Jones diameter. The optimization strategy outlined in this
      work can be easily adapted to different kinds of ions.

PMID- 22462832
TI  - Atomistic simulations of rare events using gentlest ascent dynamics.
AB  - The dynamics of complex systems often involve thermally activated barrier
      crossing events that allow these systems to move from one basin of attraction on
      the high dimensional energy surface to another. Such events are ubiquitous, but
      challenging to simulate using conventional simulation tools, such as molecular
      dynamics. Recently, E and Zhou [Nonlinearity 24(6), 1831 (2011)] proposed a set
      of dynamic equations, the gentlest ascent dynamics (GAD), to describe the escape
      of a system from a basin of attraction and proved that solutions of GAD converge
      to index-1 saddle points of the underlying energy. In this paper, we extend GAD
      to enable finite temperature simulations in which the system hops between
      different saddle points on the energy surface. An effective strategy to use GAD
      to sample an ensemble of low barrier saddle points located in the vicinity of a
      locally stable configuration on the high dimensional energy surface is proposed.
      The utility of the method is demonstrated by studying the low barrier saddle
      points associated with point defect activity on a surface. This is done for two
      representative systems, namely, (a) a surface vacancy and ad-atom pair and (b) a
      heptamer island on the (111) surface of copper.

PMID- 22462833
TI  - Calculation of electron-hole recombination probability using explicitly
      correlated Hartree-Fock method.
AB  - The electron-hole explicitly correlated Hartree-Fock method (eh-XCHF) is
      presented as a general strategy for investigation of electron-hole correlation
      and computation of electron-hole recombination probability. The eh-XCHF method is
      a variational method which uses explicitly correlated wavefunction that depends
      on the electron-hole inter-particle distances. It is shown that the explicitly
      correlated ansatz provides a systematic route to variationally minimize the total
      energy. The parabolic quantum dot is used as the benchmark system and the eh-XCHF
      method is used for computation of the ground state energy and electron-hole
      recombination probability. The results are compared to Hartree-Fock and
      explicitly correlated full configuration interaction (R12-FCI) calculations. The
      results indicate that an accurate description of the electron-hole wavefunction
      at short electron-hole inter-particle distances is crucial for qualitative
      description of the electron-hole recombination probability. The eh-XCHF method
      successfully addresses this issue and comparison of eh-XCHF calculations with R12
      FCI shows good agreement. The quality of the mean field approximation for
      electron-hole system is also investigated by comparing HF and R12-FCI energies
      for electron-electron and electron-hole systems. It was found that performance of
      the mean field approximation is worse for the electron-hole system as compared to
      the corresponding electron-electron system.

PMID- 22462834
TI  - Optimization of orbital-specific virtuals in local Moller-Plesset perturbation
      theory.
AB  - We present an orbital-optimized version of our orbital-specific-virtuals second
      order Moller-Plesset perturbation theory (OSV-MP2). The OSV model is a local
      correlation ansatz with a small basis of virtual functions for each occupied
      orbital. It is related to the Pulay-Saebo approach, in which domains of virtual
      orbitals are drawn from a single set of projected atomic orbitals; but here the
      virtual functions associated with a particular occupied orbital are specifically
      tailored to the correlation effects in which that orbital participates. In this
      study, the shapes of the OSVs are optimized simultaneously with the OSV-MP2
      amplitudes by minimizing the Hylleraas functional or approximations to it. It is
      found that optimized OSVs are considerably more accurate than the OSVs obtained
      through singular value decomposition of diagonal blocks of MP2 amplitudes, as
      used in our earlier work. Orbital-optimized OSV-MP2 recovers smooth potential
      energy surfaces regardless of the number of virtuals. Full optimization is still
      computationally demanding, but orbital optimization in a diagonal or Kapuy-type
      MP2 approximation provides an attractive scheme for determining accurate OSVs.

PMID- 22462836
TI  - A second-order perturbation theory route to vibrational averages and transition
      properties of molecules: general formulation and application to infrared and
      vibrational circular dichroism spectroscopies.
AB  - A general formulation to compute anharmonic vibrational averages and transition
      properties at the second-order of perturbation theory is derived from the
      Rayleigh-Schrodinger development. This approach is intended to be applicable to
      any property expanded as a Taylor series up to the third order with respect to
      normal coordinates or their associated momenta. The equations are straightforward
      to implement and can be easily adapted to various properties, as illustrated for
      the case of electric and magnetic dipole moments. From those, infrared and
      vibrational circular dichroism spectra can be readily obtained. This fully
      automatic procedure has been applied to several chiral molecules of small-to
      medium sizes and compared to the standard double harmonic approximation and to
      experimental data.

PMID- 22462835
TI  - The implementation of a self-consistent constricted variational density
      functional theory for the description of excited states.
AB  - We present here the implementation of a self-consistent approach to the
      calculation of excitation energies within regular Kohn-Sham density functional
      theory. The method is based on the n-order constricted variational density
      functional theory (CV(n)-DFT) [T. Ziegler, M. Seth, M. Krykunov, J. Autschbach,
      and F. Wang, J. Chem. Phys. 130, 154102 (2009)] and its self-consistent
      formulation (SCF-CV(infinity)-DFT) [J. Cullen, M. Krykunov, and T. Ziegler, Chem.
      Phys. 391, 11 (2011)]. A full account is given of the way in which SCF
      CV(infinity)-DFT is implemented. The SCF-CV(infinity)-DFT scheme is further
      applied to transitions from occupied pi orbitals to virtual pi(*) orbitals. The
      same series of transitions has been studied previously by high-level ab initio
      methods. We compare here the performance of SCF-CV(infinity)-DFT to that of time
      dependent density functional theory (TD-DFT), CV(n)-DFT and DeltaSCF-DFT, with
      the ab initio results as a benchmark standard. It is finally demonstrated how
      adiabatic TD-DFT and DeltaSCF-DFT are related through different approximations to
      SCF-CV(infinity)-DFT.

PMID- 22462837
TI  - Agglomeration of magnetic nanoparticles.
AB  - The formation of agglomerates by salt-induced double layer compression of
      magnetic nanoparticles in the absence and presence of an external magnetic field
      was investigated experimentally as well as computationally in this study. The
      structures of the agglomerates were analyzed through scanning electron microscopy
      and proved to be highly porous and composed of large spaces among the branches of
      a convoluted network. In the absence of an external magnetic field, the branches
      of such a network were observed to be oriented in no particular direction. In
      contrast, when the agglomeration process was allowed to occur in the presence of
      an external magnetic field, these branches appeared to be oriented predominantly
      in one direction. A modified Discrete Element Method was applied to simulate the
      agglomeration process of magnetic nanoparticles both in the absence and presence
      of an external magnetic field. The simulations show that agglomeration occurred
      by the formation of random clusters of nanoparticles which then joined to form a
      network. In the presence of anisotropic magnetic forces, these clusters were
      rotated to align along the direction of the magnetic field and the final network
      formed consisted largely of elongated branches of magnetic nanoparticles.

PMID- 22462838
TI  - Effect of binding on escape from cavity through narrow tunnel.
AB  - When a diffusing particle escapes from a spherical cavity through a narrow, not
      too long tunnel, the escape kinetics is essentially single-exponential. The
      presence of reversible binding sites on the cavity wall leads to retention of the
      particle in the system and converts the single-exponential kinetics into bi
      exponential. We develop a theory that describes these effects. The theory shows
      how the delay time and the average number of binding events depend on the
      geometric and kinetic parameters of the system. To study the effect of the cavity
      shape, we also analyze the kinetics when the particle escapes from a cylindrical
      cavity with reversible binding sites.

PMID- 22462839
TI  - B2-PPW91: a promising double-hybrid density functional for the electric response
      properties.
AB  - A new double-hybrid density functional, termed B2-PPW91, is presented which
      includes the Becke88 (B88) exchange in conjunction with Perdew-Wang91 (PW91)
      gradient-corrected correlation functional. The fitting parameters are obtained by
      minimization of mean absolute error of the static dipole polarizability of 4d
      transition metal monohalides against the CCSD(T)/aug-cc-pVTZ/SDD results. The
      performance of proposed functional has been assessed for estimation of other
      response properties, such as dipole moment and excitation energy, for the same
      species. We then proceed to explore the validity of B2-PPW91 method for
      calculation of the dipole polarizability of some 5d transition metal
      monofluorides. In all cases, the improvement compared to common density
      functional methods and even previously reported double-hybrid functionals such as
      B2-PLYP and mPW2-PLYP has been observed. This indicates that the utility of
      double-hybrid density functional methods can be further extended to study linear
      and non-linear optical properties of transition metal containing molecules.

PMID- 22462840
TI  - A novel computer simulation method for simulating the multiscale transduction
      dynamics of signal proteins.
AB  - Signal proteins are able to adapt their response to a change in the environment,
      governing in this way a broad variety of important cellular processes in living
      systems. While conventional molecular-dynamics (MD) techniques can be used to
      explore the early signaling pathway of these protein systems at atomistic
      resolution, the high computational costs limit their usefulness for the
      elucidation of the multiscale transduction dynamics of most signaling processes,
      occurring on experimental timescales. To cope with the problem, we present in
      this paper a novel multiscale-modeling method, based on a combination of the
      kinetic Monte-Carlo- and MD-technique, and demonstrate its suitability for
      investigating the signaling behavior of the photoswitch light-oxygen-voltage-2
      Jalpha domain from Avena Sativa (AsLOV2-Jalpha) and an AsLOV2-Jalpha-regulated
      photoactivable Rac1-GTPase (PA-Rac1), recently employed to control the motility
      of cancer cells through light stimulus. More specifically, we show that their
      signaling pathways begin with a residual re-arrangement and subsequent H-bond
      formation of amino acids near to the flavin-mononucleotide chromophore, causing a
      coupling between beta-strands and subsequent detachment of a peripheral alpha
      helix from the AsLOV2-domain. In the case of the PA-Rac1 system we find that this
      latter process induces the release of the AsLOV2-inhibitor from the switchII
      activation site of the GTPase, enabling signal activation through effector
      protein binding. These applications demonstrate that our approach reliably
      reproduces the signaling pathways of complex signal proteins, ranging from
      nanoseconds up to seconds at affordable computational costs.

PMID- 22462841
TI  - Spectral methods for the equations of classical density-functional theory:
      relaxation dynamics of microscopic films.
AB  - We propose a numerical scheme based on the Chebyshev pseudo-spectral collocation
      method for solving the integral and integro-differential equations of the density
      functional theory and its dynamic extension. We demonstrate the exponential
      convergence of our scheme, which typically requires much fewer discretization
      points to achieve the same accuracy compared to conventional methods. This
      discretization scheme can also incorporate the asymptotic behavior of the
      density, which can be of interest in the investigation of open systems. Our
      scheme is complemented with a numerical continuation algorithm and an appropriate
      time stepping algorithm, thus constituting a complete tool for an efficient and
      accurate calculation of phase diagrams and dynamic phenomena. To illustrate the
      numerical methodology, we consider an argon-like fluid adsorbed on a Lennard
      Jones planar wall. First, we obtain a set of phase diagrams corresponding to the
      equilibrium adsorption and compare our results obtained from different
      approximations to the hard sphere part of the free energy functional. Using
      principles from the theory of sub-critical dynamic phase field models, we
      formulate the time-dependent equations which describe the evolution of the
      adsorbed film. Through dynamic considerations we interpret the phase diagrams in
      terms of their stability. Simulations of various wetting and drying scenarios
      allow us to rationalize the dynamic behavior of the system and its relation to
      the equilibrium properties of wetting and drying.

PMID- 22462842
TI  - Explicitly correlated Wn theory: W1-F12 and W2-F12.
AB  - In an attempt to extend the applicability of the W1 and W2 ab initio
      computational thermochemistry methods, we propose explicitly correlated versions
      thereof, denoted W1-F12 and W2-F12. In W2-F12, we can "save" one cardinal number
      (viz., angular momentum) in the basis set sequences without loss in accuracy; in
      W1-F12, we can do so for first-row compounds but not for second-row compounds. At
      a root mean square deviation (RMSD) = 0.19 kcal/mol for the first-row molecules
      in the W4-11 benchmark dataset, W1-F12 is in fact superior to ordinary W1 theory.
      For the entire W4-11 set, W2-F12 yields a RMSD = 0.20 kcal/mol, comparable to
      0.19 kcal/mol from ordinary W2 theory. The extended applicability ranges of W1
      F12 and W2-F12 are not just due to the lower computational cost but also to
      greatly reduced memory and especially storage requirements. They are illustrated
      through applications to nucleic acids and to polyacenes (with up to four rings),
      for which the following revised gas-phase heats of formation are found:
      Delta(f)H(298)(?) = 19.6 (benzene), 34.94 (naphthalene), 53.9, (anthracene), 73.9
      (naphthacene/tetracene), 54.9 (adenine), -16.3 (cytosine), 5.1 (guanine), -80.6
      (thymine), and -71.6 (uracil) kcal/mol. Our theoretical values for the DNA/RNA
      bases largely confirm recent predictions based on much lower-level calculations.
      The W1-F12 theoretical values for benzene, naphthalene, and anthracene are in
      very good to reasonable agreement with experiment. However, both W1-F12 and other
      computational estimates show that the accepted experimental value for naphthacene
      cannot be reconciled with those for the lower acenes: we suggest that
      Delta(f)H(298)(?)[naphthacene(g)] = 74.25 +/- 1 kcal/mol is a more realistic
      estimate.

PMID- 22462843
TI  - Energy expressions for Kohn-Sham potentials and their relation to the Slater
      Janak theorem.
AB  - Direct approximation of exchange-correlation potentials is a promising approach
      to accurate prediction of molecular response properties. However, little is known
      about ways of obtaining total energies from model potentials other than by using
      the Levy-Perdew virial relation. We introduce and explore several alternative
      formulas which arise as line integrals of potentials taken along density scaling
      and aufbau-filling paths, and which are not limited to the exchange term. The
      relaxed-orbital variant of the aufbau-path energy expression is shown to be
      closely related to the Slater-Janak theorem. Although the Levy-Perdew relation
      generally yields reasonable energies for all model exchange potentials, the
      relaxed-orbital aufbau path gives better results for those potentials that
      predict accurate highest-occupied orbital eigenvalues, such as the potential of
      Rasanen, Pittalis, and Proetto [J. Chem. Phys. 132, 044112 (2010)]. The ideas
      presented in this work may guide the development of new types of density
      functional approximations for exchange and correlation.

PMID- 22462844
TI  - Approaching chemical accuracy with quantum Monte Carlo.
AB  - A quantum Monte Carlo study of the atomization energies for the G2 set of
      molecules is presented. Basis size dependence of diffusion Monte Carlo
      atomization energies is studied with a single determinant Slater-Jastrow trial
      wavefunction formed from Hartree-Fock orbitals. With the largest basis set, the
      mean absolute deviation from experimental atomization energies for the G2 set is
      3.0 kcal/mol. Optimizing the orbitals within variational Monte Carlo improves the
      agreement between diffusion Monte Carlo and experiment, reducing the mean
      absolute deviation to 2.1 kcal/mol. Moving beyond a single determinant Slater
      Jastrow trial wavefunction, diffusion Monte Carlo with a small complete active
      space Slater-Jastrow trial wavefunction results in near chemical accuracy. In
      this case, the mean absolute deviation from experimental atomization energies is
      1.2 kcal/mol. It is shown from calculations on systems containing phosphorus that
      the accuracy can be further improved by employing a larger active space.

PMID- 22462845
TI  - Electron correlation contribution to the physisorption of CO on MgF2(110).
AB  - We have performed CCSD(T), MP2, and DF-LMP2 calculations of the interaction
      energy of CO on the MgF(2)(110) surface by applying the method of increments and
      an embedded cluster model. In addition, we performed periodic HF, B3LYP, and DF
      LMP2 calculations and compare them to the cluster results. The incremental
      CCSD(T) calculations predict an interaction energy of E(int) = -0.37 eV with a C
      down orientation of CO above a Mg(2+) ion at the surface with a basis set of VTZ
      quality. We find that electron correlation constitutes about 50% of the binding
      energy and a detailed evaluation of the increments shows that the largest
      contribution to the correlation energy originates from the CO interaction with
      the closest F ions on the second layer.

PMID- 22462846
TI  - Optimal control of open quantum systems: a combined surrogate hamiltonian optimal
      control theory approach applied to photochemistry on surfaces.
AB  - In this paper, control of open quantum systems with emphasis on the control of
      surface photochemical reactions is presented. A quantum system in a condensed
      phase undergoes strong dissipative processes. From a theoretical viewpoint, it is
      important to model such processes in a rigorous way. In this work, the
      description of open quantum systems is realized within the surrogate hamiltonian
      approach [R. Baer and R. Kosloff, J. Chem. Phys. 106, 8862 (1997)]. An efficient
      and accurate method to find control fields is optimal control theory (OCT) [W.
      Zhu, J. Botina, and H. Rabitz, J. Chem. Phys. 108, 1953 (1998); Y. Ohtsuki, G.
      Turinici, and H. Rabitz, J. Chem. Phys. 120, 5509 (2004)]. To gain control of
      open quantum systems, the surrogate hamiltonian approach and OCT, with time
      dependent targets, are combined. Three open quantum systems are investigated by
      the combined method, a harmonic oscillator immersed in an ohmic bath, CO adsorbed
      on a platinum surface, and NO adsorbed on a nickel oxide surface. Throughout this
      paper, atomic units, i.e., h = m(e) = e = a(0) = 1, have been used unless
      otherwise stated.

PMID- 22462847
TI  - A multi-configurational time-dependent Hartree approach to the eigenstates of
      multi-well systems.
AB  - A rigorous and efficient approach for the calculation of eigenstates in
      polyatomic molecular systems with potentials displaying multiple wells is
      introduced. The scheme is based on the multi-configurational time-dependent
      Hartree (MCTDH) approach and uses multiple MCTDH wavefunctions with different
      single-particle function bases to describe the quantum dynamics in the different
      potential wells. More specifically, an iterative block Lanczos-type
      diagonalization scheme utilizing state-averaged MCTDH wavefunctions localized in
      different wells is employed to obtain the energy eigenvalues and eigenstates. The
      approach does not impose any formal restriction on the symmetry of the potential
      or the number of wells. A seven-dimensional model system of tetrahedral symmetry,
      which is inspired by A.CH(4) type complexes and displays four equivalent
      potential minima, is used to study the numerical performance of the new approach.
      It is found that the number of configurations in the MCTDH wavefunctions required
      to obtain converged results is decreased by roughly one order of magnitude
      compared to standard MCTDH calculations employing a block-relaxation scheme.

PMID- 22462848
TI  - Optimal pairwise and non-pairwise alchemical pathways for free energy
      calculations of molecular transformation in solution phase.
AB  - We estimate the global minimum variance path for computing the free energy
      insertion into or deletion of small molecules from a dense fluid. We perform this
      optimization over all pair potentials, irrespective of functional form, using
      functional optimization with a two-body approximation for the radial distribution
      function. Surprisingly, the optimal pairwise path obtained via this method is
      almost identical to the path obtained using a optimized generalized "soft core"
      potential reported by Pham and Shirts [J. Chem. Phys. 135, 034114 (2011)]. We
      also derive the lowest variance non-pairwise potential path for molecular
      insertion or deletion and compare its efficiency to the pairwise path. Under
      certain conditions, non-pairwise pathways can reduce the total variance by up to
      60% compared to optimal pairwise pathways. However, optimal non-pairwise pathways
      do not appear generally feasible for practical free energy calculations because
      an accurate estimate of the free energy, the parameter that is itself is desired,
      is required for constructing this non-pairwise path. Additionally, simulations at
      most intermediate states of these non-pairwise paths have significantly longer
      correlation times, often exceeding standard simulation lengths for solvation of
      bulky molecules. The findings suggest that the previously obtained soft core
      pathway is the lowest variance pathway for molecular insertion or deletion in
      practice. The findings also demonstrate the utility of functional optimization
      for determining the efficiency of thermodynamic processes performed with
      molecular simulation.

PMID- 22462849
TI  - Spin-adapted density matrix renormalization group algorithms for quantum
      chemistry.
AB  - We extend the spin-adapted density matrix renormalization group (DMRG) algorithm
      of McCulloch and Gulacsi [Europhys. Lett. 57, 852 (2002)] to quantum chemical
      Hamiltonians. This involves using a quasi-density matrix, to ensure that the
      renormalized DMRG states are eigenfunctions of S(2), and the Wigner-Eckart
      theorem, to reduce overall storage and computational costs. We argue that the
      spin-adapted DMRG algorithm is most advantageous for low spin states.
      Consequently, we also implement a singlet-embedding strategy due to Tatsuaki
      [Phys. Rev. E 61, 3199 (2000)] where we target high spin states as a component of
      a larger fictitious singlet system. Finally, we present an efficient algorithm to
      calculate one- and two-body reduced density matrices from the spin-adapted
      wavefunctions. We evaluate our developments with benchmark calculations on
      transition metal system active space models. These include the Fe(2)S(2),
      [Fe(2)S(2)(SCH(3))(4)](2-), and Cr(2) systems. In the case of Fe(2)S(2), the spin
      ladder spacing is on the microHartree scale, and here we show that we can target
      such very closely spaced states. In [Fe(2)S(2)(SCH(3))(4)](2-), we calculate
      particle and spin correlation functions, to examine the role of sulfur bridging
      orbitals in the electronic structure. In Cr(2) we demonstrate that spin
      adaptation with the Wigner-Eckart theorem and using singlet embedding can yield
      up to an order of magnitude increase in computational efficiency. Overall, these
      calculations demonstrate the potential of using spin-adaptation to extend the
      range of DMRG calculations in complex transition metal problems.

PMID- 22462850
TI  - Water density and polarizability deduced from the refractive index determined by
      interferometric measurements up to 250 MPa.
AB  - The refractive index of water is precisely determined in the visible light range
      as a function of the pressure until 250 MPa by means of a new measurement device
      that uses a special pipe tee included in an interferometer set. This technique
      allows revisiting the Bradley-Tait and Sellmeier equations to make them dependent
      on the wavelength and the pressure, respectively. The Bradley-Tait equation for
      the pressure dependence of the water refractive index is completed by a
      wavelength-dependent factor. Also, in the considered pressure and wavelength
      ranges, it is shown that the Sellmeier coefficients can be straightforwardly
      linked to the pressure, allowing the determination of the refractive index of
      water for either any wavelength or pressure. A new simple model allows the
      determination of the density of water as a function of the measured refractive
      index. Finally, the polarizability of water as function of pressure and
      wavelength is calculated by means of the Lorentz-Lorenz equation.

PMID- 22462851
TI  - Photoelectron spectra and structures of three cyclic dipeptides: PhePhe, TyrPro,
      and HisGly.
AB  - We have investigated the electronic structure of three cyclic dipeptides:
      cyclo(Histidyl-Glycyl) (cHisGly), cyclo(Tyrosyl-Prolyl) (cTyrPro), and
      cyclo(Phenylalanyl-Phenylalanyl) (cPhePhe) in the vapor phase, by means of
      photoemission spectroscopy and theoretical modeling. The last compound was
      evaporated from the solid linear dipeptide, but cyclised, losing water to form
      cPhePhe in the gas phase. The results are compared with our previous studies of
      three other cyclopeptides. Experimental valence and core level spectra have been
      interpreted in the light of calculations to identify the basic chemical
      properties associated with the central diketopiperazine ring, and with the
      additional functional groups. The valence spectra are generally characterized by
      a restricted set of outer valence orbitals separated by a gap from most other
      valence orbitals. The theoretically simulated core and valence spectra of all
      three cyclic dipeptides agree reasonably well with the experimental spectra. The
      central ring and the side chains act as independent chromophores whose spectra do
      not influence one another, except for prolyl dipeptides, where the pyrrole ring
      is fused with the central ring. In this case, significant changes in the valence
      and core level spectra were observed, and explained by stronger hybridization of
      the valence orbitals.

PMID- 22462852
TI  - Vibrational effects on the electron momentum distributions of valence orbitals of
      formamide.
AB  - The ionization energy spectra and electron momentum distributions of formamide
      were investigated using the high-resolution electron momentum spectrometer in
      combination with high level calculations. The observed ionization energy spectra
      and electron momentum distributions were interpreted using symmetry adapted
      cluster-configuration interaction theory, outer valence Green function, and DFT
      B3LYP methods. The ordering of 10a(') and 2a(") orbitals of formamide was
      assigned unambiguously by comparing the experimental electron momentum
      distributions with the corresponding theoretical results, i.e., 10a(') has a
      lower binding energy. In addition, it was found that the low-frequency wagging
      vibration of the amino group at room temperature has noticeable effects on the
      electron momentum distributions. The equilibrium-nuclear-positions-approximation,
      which was widely used in electron momentum spectroscopy, is not accurate for
      formamide molecule. The calculations based on the thermal average can evidently
      improve the agreement with the experimental momentum distributions.

PMID- 22462853
TI  - The mechanism of emerging catalytic activity of gold nano-clusters on rutile
      TiO2(110) in CO oxidation reaction.
AB  - This paper reveals the fact that the O adatoms (O(ad)) adsorbed on the 5-fold Ti
      rows of rutile TiO(2)(110) react with CO to form CO(2) at room temperature and
      the oxidation reaction is pronouncedly enhanced by Au nano-clusters deposited on
      the above O-rich TiO(2)(110) surfaces. The optimum activity is obtained for 2D
      clusters with a lateral size of ~1.5 nm and two-atomic layer height corresponding
      to ~50 Au atoms/cluster. This strong activity emerging is attributed to an
      electronic charge transfer from Au clusters to O-rich TiO(2)(110) supports
      observed clearly by work function measurement, which results in an interface
      dipole. The interface dipoles lower the potential barrier for dissociative O(2)
      adsorption on the surface and also enhance the reaction of CO with the O(ad)
      atoms to form CO(2) owing to the electric field of the interface dipoles, which
      generate an attractive force upon polar CO molecules and thus prolong the
      duration time on the Au nano-clusters. This electric field is screened by the
      valence electrons of Au clusters except near the perimeter interfaces, thereby
      the activity is diminished for three-dimensional clusters with a larger size.

PMID- 22462854
TI  - Ab initio many-electron study for the low-lying states of the alkali hydride
      cations in the adiabatic representation.
AB  - An ab initio multireference single- and double-excitation configuration
      interaction (CI) study is carried out for the ground and excited electronic
      states of alkali-hydride cations (LiH(+), NaH(+), KH(+), RbH(+), and CsH(+)). For
      all alkali-metal atoms, the first inner-shell and valence electrons (nine active
      electrons, three for Li) are considered explicitly in the ab initio self
      consistent-field and CI calculations. The adiabatic potential energy curves,
      radial and rotational couplings are calculated and presented. Short-range (~3
      a.u.) potential wells produced by the excitation of the inner-shell electrons are
      found. The depths of the inner potential wells are much greater than those of the
      outer wells for the CsH(+) system. The computed spectroscopic constants for the
      long-range potential well of the 2 (2)Sigma(+) state are very close to the
      available theoretical and experimental data. The electronic states of alkali
      hydrogen cations are also compared with each other, it is found that the
      positions of the potential wells shift to larger internuclear distances
      gradually, and the depths of these potential wells become greater with increasing
      alkali-metal atomic number. The relationships between structures of the radial
      coupling matrix elements and the avoiding crossings of the potential curves are
      analyzed. From NaH(+) to CsH(+), radial coupling matrix elements display more and
      more complex structures due to the gradual decrease of energy separations for
      avoided crossings. Finally, the behavior of some rotational couplings is also
      shown.

PMID- 22462855
TI  - Positron scattering from the cyclic ethers oxirane, 1,4-dioxane, and
      tetrahydropyran.
AB  - In this paper we report original measurements of total cross sections (TCSs) for
      positron scattering from the cyclic ethers oxirane (C(2)H(4)O), 1,4-dioxane
      (C(4)H(8)O(2)), and tetrahydropyran (C(5)H(10)O). The present experiments focus
      on the low energy range from ~0.2  to  50 eV, with an energy resolution smaller
      than 300 meV. This study concludes our systematic investigation into TCSs for a
      class of organic compounds that can be thought of as sub-units or moieties to the
      nucleotides in living matter, and which as a consequence have become topical for
      scientists seeking to simulate particle tracks in matter. Note that as TCSs
      specify the mean free path between collisions in such simulations, they have
      enjoyed something of a recent renaissance in interest because of that
      application. For oxirane, we also report original Schwinger multichannel elastic
      integral cross section (ICS) calculations at the static and static plus
      polarisation levels, and with and without Born-closure that attempts to account
      for the permanent dipole moment of C(2)H(4)O. Those elastic ICSs are computed for
      the energy range 0.5-10 eV. To the best of our knowledge, there are no other
      experimental results or theoretical calculations against which we can compare the
      present positron TCSs. However, electron TCSs for oxirane (also known as ethylene
      oxide) and tetrahydropyran do currently exist in the literature and a comparison
      to them for each species will be presented.

PMID- 22462856
TI  - A comparative computational study of FKrCCH...Y, FCCKrH...Y, and FCCH...Y
      complexes (Y = BF, CO, N2, OH2, OH(CH3), O(CH3)2).
AB  - The structural and spectroscopic changes in complexes of FCCKrH...Y and
      FKrCCH...Y (Y = BF, CO, N(2), OH(2), OH(CH(3)), O(CH(3))(2)) were computed at the
      MP2/6-31++G(d,p) level of theory and compared with the corresponding properties
      for FCCH...Y. The computed bond length changes and frequency shifts on
      complexation were rationalized by comparing with a perturbation model, which
      gives quantitative agreement with the standard ab initio results. A recently
      proposed model also gives a reasonable qualitative account of the observed trends
      in these complexes.

PMID- 22462857
TI  - Kinetics of electron attachment to OH and HNO3 and mutual neutralization of Ar+
      with NO2(-) and NO3(-) at 300 and 500 K.
AB  - The electron attachment rate constant to nitric acid (HNO(3)) has been measured
      in a flowing afterglow-Langmuir probe (FALP) apparatus at 300 and 500 K using
      three independent methods: the traditional FALP technique of monitoring electron
      depletion, "one-gas" VENDAMS (variable electron and neutral density attachment
      mass spectrometry), and "two-gas" VENDAMS. The three measurements are in
      agreement with a 300 K weighted average of 1.4 +/- 0.3 * 10(-7) cm(3) s(-1), 2 to
      10 times higher than previously reported values. Attachment is primarily
      dissociative yielding NO(2)(-) as previously reported, but for the first time a
      small endothermic channel to produce OH(-) was also observed at 500 K. From the
      one-gas VENDAMS data, associative attachment to the OH produced in the primary
      attachment was found to occur with an effective two body rate constant of 1.2+/
      (0.7) (3)*10(-11) cm(3) s(-1) at 300 K, the first reported rate constant for this
      radical species. Finally, ion-ion neutralization rate constants of NO(2)(-) and
      NO(3)(-) with Ar(+) were determined to be 5.2+/-(2.5) (1.5) * 10(-8) and 4.5 +/-
      2.5 * 10(-8) cm(3) s(-1) at 300 K, respectively.

PMID- 22462858
TI  - Nonpolar nitrous oxide dimer: observation of combination bands of (14N2O)2 and
      (15N2O)2 involving the torsion and antigeared bending modes.
AB  - Spectra of the nonpolar nitrous oxide dimer in the region of the N(2)O nu(1)
      fundamental band were observed in a supersonic slit-jet apparatus. The expansion
      gas was probed using radiation from a quantum cascade or a tunable diode laser,
      with both lasers employed in a rapid-scan signal averaging mode. Four bands were
      observed and analyzed: new combination bands involving the intermolecular
      conrotation of the monomers (A(g) antigeared bend) for ((14)N(2)O)(2) and
      ((15)N(2)O)(2), the previously reported torsional combination band for
      ((14)N(2)O)(2) with improved signal-to-noise ratio, and the same torsional
      combination band for ((15)N(2)O)(2). The resulting frequencies for the
      intermolecular antigeared mode are 96.0926(1) and 95.4912(1) cm(-1) for
      ((14)N(2)O)(2) and ((15)N(2)O)(2), respectively. This is the third of the four
      intermolecular frequencies which has now been measured experimentally, the others
      being the out-of-plane torsion and the geared bend modes. Our experimental
      results are in good agreement with two recent high level ab initio theoretical
      calculations.

PMID- 22462859
TI  - Electronic excitations in long polyenes revisited.
AB  - We apply the valence shell model OM2 [W. Weber and W. Thiel, Theor. Chem. Acc.
      103, 495, (2000)] combined with multireference configuration interaction (MRCI)
      to compute the vertical excitation energies and transition dipole moments of the
      low-energy singlet excitations in the polyenes with 4 <= N <= 22pi-electrons. We
      find that the OM2/MRCI descriptions closely resemble those of Pariser-Parr-Pople
      (PPP) pi-electron models [P. Tavan and K. Schulten, Phys. Rev. B 36, 4337,
      (1987)], if equivalent MRCI procedures and regularly alternating model geometries
      are used. OM2/MRCI optimized geometries are shown to entail improved descriptions
      particularly for smaller polyenes (N <= 12), for which sizeable deviations from
      the regular model geometries are found. With configuration interaction active
      spaces covering also the sigma- in addition to the pi-electrons, OM2/MRCI
      excitation energies turn out to become smaller by at most 0.35 eV for the ionic
      and 0.15 eV for the covalent excitations. The particle-hole (ph) symmetry, which
      in Pariser-Parr-Pople models arises from the zero-differential overlap
      approximation, is demonstrated to be only weakly broken in OM2 such that the
      oscillator strengths of the covalent 1B(u)(-) states, which artificially vanish
      in ph-symmetric models, are predicted to be very small. According to OM2/MRCI and
      experimental data the 1B(u)(-) state is the third excited singlet state for N <
      12 and becomes the second for N >= 14. By comparisons with results of other
      theoretical approaches and experimental evidence we argue that deficiencies of
      the particular MRCI method employed by us, which show up in a poor size
      consistency of the covalent excitations for N > 12, are caused by its restriction
      to at most doubly excited references.

PMID- 22462860
TI  - Determining the dissociation threshold of ammonia trimers from action
      spectroscopy of small clusters.
AB  - Infrared-action spectroscopy of small ammonia clusters obtained by detecting
      ammonia fragments from vibrational predissociation provides an estimate of the
      dissociation energy of the trimer. The product detection uses resonance enhanced
      multiphoton ionization (REMPI) of individual rovibrational states of ammonia
      identified by simulations using a consistent set of ground-electronic-state
      spectroscopic constants in the PGOPHER program. Comparison of the infrared-action
      spectra to a less congested spectrum measured in He droplets [M. N. Slipchenko,
      B. G. Sartakov, A. F. Vilesov, and S. S. Xantheas, J. Phys. Chem. A 111, 7460
      (2007)] identifies the contributions from the dimer and the trimer. The relative
      intensities of the dimer and trimer features in the infrared-action spectra
      depend on the amount of energy available for breaking the hydrogen bonds in the
      cluster, a quantity that depends on the energy content of the detected fragment.
      Infrared-action spectra for ammonia fragments with large amounts of internal
      energy have almost no trimer component because there is not enough energy
      available to break two bonds in the cyclic trimer. By contrast, infrared-action
      spectra for fragments with low amounts of internal energy have a substantial
      trimer component. Analyzing the trimer contribution quantitatively shows that
      fragmentation of the trimer into a monomer and dimer requires an energy of 1700
      to 1800 cm(-1), a range that is consistent with several theoretical estimates.

PMID- 22462861
TI  - An isotopic-independent highly accurate potential energy surface for CO2
      isotopologues and an initial (12)C(16)O2 infrared line list.
AB  - An isotopic-independent, highly accurate potential energy surface (PES) has been
      determined for CO(2) by refining a purely ab initio PES with selected, purely
      experimentally determined rovibrational energy levels. The purely ab initio PES
      is denoted Ames-0, while the refined PES is denoted Ames-1. Detailed tests are
      performed to demonstrate the spectroscopic accuracy of the Ames-1 PES. It is
      shown that Ames-1 yields sigma(rms) (root-mean-squares error) = 0.0156 cm(-1) for
      6873 J = 0-117 (12)C(16)O(2) experimental energy levels, even though less than
      500 (12)C(16)O(2) energy levels were included in the refinement procedure. It is
      also demonstrated that, without any additional refinement, Ames-1 yields very
      good agreement for isotopologues. Specifically, for the (12)C(16)O(2) and
      (13)C(16)O(2) isotopologues, spectroscopic constants G(v) computed from Ames-1
      are within +/-0.01 and 0.02 cm(-1) of reliable experimentally derived values,
      while for the (16)O(12)C(18)O, (16)O(12)C(17)O, (16)O(13)C(18)O, (16)O(13)C(17)O,
      (12)C(18)O(2), (17)O(12)C(18)O, (12)C(17)O(2), (13)C(18)O(2), (13)C(17)O(2),
      (17)O(13)C(18)O, and (14)C(16)O(2) isotopologues, the differences are between +/
      0.10 and 0.15 cm(-1). To our knowledge, this is the first time a polyatomic PES
      has been refined using such high J values, and this has led to new challenges in
      the refinement procedure. An initial high quality, purely ab initio dipole moment
      surface (DMS) is constructed and used to generate a 296 K line list. For most
      bands, experimental IR intensities are well reproduced for (12)C(16)O(2) using
      Ames-1 and the DMS. For more than 80% of the bands, the experimental intensities
      are reproduced with sigma(rms)(DeltaI) < 20% or sigma(rms)(DeltaI/delta(obs)) <
      5. A few exceptions are analyzed and discussed. Directions for future
      improvements are discussed, though it is concluded that the current Ames-1 and
      the DMS should be useful in analyzing and assigning high-resolution laboratory or
      astronomical spectra.

PMID- 22462862
TI  - Spin-orbit quenching of Cl(2P(1/2)) by H2.
AB  - We report fully-quantum, time-independent, scattering calculations for the spin
      orbit quenching of Cl((2)P(1/2)) by H(2) molecules at low and moderate
      temperature. Our calculations take into account chemical reaction channels. Cross
      sections are calculated for total energies up to 5000 cm(-1) which are used to
      determine, by thermal averaging, state-to-state rate coefficients at temperatures
      ranging from 50 to 500 K. Spin-orbit relaxation of chlorine is dominated by
      collisions with H(2) in the rotationally excited states j = 2 and j = 3. In the
      former case the near-resonant energy transfer is the primary relaxation
      mechanism. The inclusion of the reactive channel could lead differences compared
      to pure inelastic calculations. Good agreement is obtained with experimental
      relaxation measurements at room temperature.

PMID- 22462863
TI  - UV photodissociation dynamics of iodobenzene: effects of fluorination.
AB  - The UV photochemistry of various fluorinated iodobenzenes (4-fluoro-, 2,4
      difluoro-, 3,5-difluoro-, and perfluoro-iodobenzene) has been investigated at
      many wavelengths by velocity map imaging, time-resolved near infrared absorption
      spectroscopy and (spin-orbit resolved) ab initio calculations of the ground and
      excited state potentials along the C-I stretch coordinate, R(C-I). The textbook
      description of the near UV photochemistry of CH(3)I, i.e., sigma*<-n excitation
      to the (3)Q(0+) state, followed by direct dissociation (to yield spin-orbit
      excited iodine atom (I*) products) or by non-adiabatic coupling via a conical
      intersection (CI) with the (1)Q(1) potential (to yield ground state iodine (I)
      atoms) is shown to provide a good zero-order model for aryl iodide photochemistry
      also. However, the aryl halides also possess occupied pi and low-lying pi*
      orbitals, and have lower (C(2v) or C(s)) symmetry than CH(3)I. Both of these
      factors introduce additional subtleties. For example, excitations to and
      predissociation of pipi* excited states provide additional routes to I products,
      most obviously at long UV wavelengths. nsigma*/pisigma* configuration mixing
      stabilizes the (analogue of the) (3)Q(0+) potential energy surface (PES), to an
      extent that scales with the degree of fluorination; the corresponding 4A(1) PES
      in C(6)F(5)I is actually predicted to exhibit a minimum at extended R(C-I). This
      has the effect of extending the long wavelength threshold for forming I*
      products. The lowered symmetry enables an additional (sloped) CI with the 5A(2)
      (9A(") in 2,4-difluorobenzene) PES, which provides an extra non-adiabatic route
      to (fast) ground state I atoms when populating the 4A(1) PES at shorter UV
      excitation wavelengths.

PMID- 22462864
TI  - The solvation of two electrons in the gaseous clusters of Na- (NH3)n and Li-
      (NH3)n.
AB  - Alkali metal ammonia clusters, in their cationic, neutral, and anionic form, are
      molecular models for the alkali-ammonia solutions, which have rich variation of
      phases with the solvated electrons playing an important role. With two s
      electrons, the Na(-)(NH(3))(n) and Li(-)(NH(3))(n) clusters are unique in that
      they capture the important aspect of the coupling between two solvated electrons.
      By first principles calculations, we demonstrate that the two electrons are
      detached from the metal by n = 10, which produces a cluster with a solvated
      electron pair in the vicinity of a solvated alkali cation. The coupling of the
      two electrons leads to either the singlet or triplet state, both of which are
      stable. They are also quite distinct from the hydrated anionic clusters Na(
      )(H(2)O)(n) and Li(-)(H(2)O)(n), in that the solvated electrons are delocalized
      and widely distributed among the solvent ammonia molecules. The Na(-)(NH(3))(n)
      and Li(-)(NH(3))(n) series, therefore, provide another interesting type of
      molecular model for the investigation of solvated electron pairs.

PMID- 22462865
TI  - M + Ng potential energy curves including spin-orbit coupling for M = K, Rb, Cs
      and Ng = He, Ne, Ar.
AB  - The X(2)Sigma(1/2)(+), A(2)Pi(1/2), A(2)Pi(3/2), and B(2)Sigma(1/2)(+) potential
      energy curves and associated dipole matrix elements are computed for M + Ng at
      the spin-orbit multi-reference configuration interaction level, where M = K, Rb,
      Cs and Ng = He, Ne, Ar. Dissociation energies and equilibrium positions for all
      minima are identified and corresponding vibrational energy levels are computed.
      Difference potentials are used together with the quasistatic approximation to
      estimate the position of satellite peaks of collisionally broadened D2 lines. The
      comparison of potential energy curves for different alkali atom and noble gas
      atom combinations is facilitated by using the same level of theory for all nine M
      + Ng pairs.

PMID- 22462866
TI  - Speed dependence of collisional relaxation in ground vibrational state of OCS:
      rotational behaviour.
AB  - Accurate experimental data on pressure broadened profiles of (16)O(12)C(32)S pure
      rotational lines in a broad range of quantum number J have been analyzed taking
      into account the speed dependence of collisional relaxation. Refined values of
      collisional self-broadening coefficients are determined and compared to
      previously known data. New quantitative information on departures of observed
      line shapes from the traditional Voigt profile is obtained. It is shown that
      these departures result mainly from the speed dependence of collisional
      relaxation. Theoretical calculations of self-broadening parameters are performed
      in the framework of the semiclassical impact Robert-Bonamy formalism where the
      mean relative molecular speed as well as the Maxwell-Boltzmann distribution of
      relative speeds is considered. The necessity of allowance for the speed
      dependence in line shape models is confirmed and satisfactory results have been
      obtained by arbitrarily limiting the integration of the differential cross
      section to a finite value of the impact parameter. It is shown for the first time
      for the whole rotational spectrum that speed dependent models not only improve
      accuracy of modeling the observed line profiles but also give physically grounded
      values of collisional relaxation parameters.

PMID- 22462867
TI  - Ultrafast internal conversion in ethylene. II. Mechanisms and pathways for
      quenching and hydrogen elimination.
AB  - Through a combined experimental and theoretical approach, we study the
      nonadiabatic dynamics of the prototypical ethylene (C(2)H(4)) molecule upon pi ->
      pi(*) excitation with 161 nm light. Using a novel experimental apparatus, we
      combine femtosecond pulses of vacuum ultraviolet and extreme ultraviolet (XUV)
      radiation with variable delay to perform time resolved photo-ion fragment
      spectroscopy. In this second part of a two part series, the XUV (17 eV < hnu < 23
      eV) probe pulses are sufficiently energetic to break the C-C bond in
      photoionization, or to photoionize the dissociation products of the vibrationally
      hot ground state. The experimental data is directly compared to excited state ab
      initio molecular dynamics simulations explicitly accounting for the probe step.
      Enhancements of the CH(2)(+) and CH(3)(+) photo-ion fragment yields,
      corresponding to molecules photoionized in ethylene (CH(2)CH(2)) and ethylidene
      (CH(3)CH) like geometries are observed within 100 fs after pi -> pi(*)
      excitation. Quantitative agreement between theory and experiment on the relative
      CH(2)(+) and CH(3)(+) yields provides experimental confirmation of the
      theoretical prediction of two distinct conical intersections and their branching
      ratio [H. Tao, B. G. Levine, and T. J. Martinez, J. Phys. Chem. A. 113, 13656
      (2009)]. Evidence for fast, non-statistical, elimination of H(2) molecules and H
      atoms is observed in the time resolved H(2)(+) and H(+) signals.

PMID- 22462869
TI  - On the theoretical determination of the Prigogine-Defay ratio in glass
      transition.
AB  - In a recent analysis [J. W. P. Schmelzer and I. Gutzow, J. Chem. Phys. 125,
      184511 (2006)] it was shown for the first time that--in contrast to earlier
      belief arising from the works of Prigogine and Defay [Chemical Thermodynamics
      (Longman, London, 1954), Chap. 19; The first French edition of this book was
      published in 1950] and Davies and Jones [Adv. Phys. 2, 370 (1953); and Proc. R.
      Soc. London, Ser. A 217, 26 (1953)]--a satisfactory theoretical interpretation of
      the experimentally observed values of the so-called Prigogine-Defay ratio Pi,
      being a combination of jumps of thermodynamic coefficients at glass transition,
      can be given employing only one structural order parameter. According to this
      analysis, this ratio has to be, in full agreement with experimental findings,
      larger than one (Pi > 1). Its particular value depends both on the thermodynamic
      properties of the system under consideration and on cooling and heating rates.
      Based on above-mentioned analysis, latter dependence on cooling rates has been
      studied in detail in another own preceding paper [T. V. Tropin, J. W. P.
      Schmelzer, and C. Schick, J. Non-Cryst. Solids 357, 1303 (2011)]. In the present
      analysis, an alternative general method of determination of the Prigogine-Defay
      ratio is outlined, allowing one to determine this ratio having at ones disposal
      the generalized equation of state of the glass-forming melts under consideration
      and, in particular, the knowledge of the equilibrium properties of the melts in
      the glass transformation range. Employing, as an illustration of the method, a
      particular model for the description of glass-forming melts, theoretical
      estimates are given for this ratio being, again, in good agreement with
      experimental data.

PMID- 22462868
TI  - Hofmeister anionic effects on hydration electric fields around water and peptide.
AB  - Specific ion effects on water dynamics and local solvation structure around a
      peptide are important in understanding the Hofmeister series of ions and their
      effects on protein stability in aqueous solution. Water dynamics is essentially
      governed by local hydrogen-bonding interactions with surrounding water molecules
      producing hydration electric field on each water molecule. Here, we show that the
      hydration electric field on the OD bond of HOD molecule in water can be directly
      estimated by measuring its OD stretch infrared (IR) radiation frequency shift
      upon increasing ion concentration. For a variety of electrolyte solutions
      containing Hofmeister anions, we measured the OD stretch IR bands and estimated
      the hydration electric field on the OD bond to be about a hundred MV/cm with
      standard deviation of tens of MV/cm. As anion concentration increases from 1 to 6
      M, the hydration electric field on the OD bond decreases by about 10%, indicating
      that the local H-bond network is partially broken by dissolved ions. However, the
      measured hydration electric fields on the OD bond and its fluctuation amplitudes
      for varying anions are rather independent on whether the anion is a kosmotrope or
      a chaotrope. To further examine the Hofmeister effects on H-bond solvation
      structure around a peptide bond, we examined the amide I' and II' mode
      frequencies of N-methylacetamide in various electrolyte D(2)O solutions. It is
      found that the two amide vibrational frequencies are not affected by ions,
      indicating that the H-bond solvation structure in the vicinity of a peptide
      remains the same irrespective of the concentration and character of ions. The
      present experimental results suggest that the Hofmeister anionic effects are not
      caused by direct electrostatic interactions of ions with peptide bond or water
      molecules in its first solvation shell. Furthermore, even though the H-bond
      network of water is affected by ions, thus induced change of local hydration
      electric field on the OD bond of HOD is not in good correlation with the well
      known Hofmeister series. We anticipate that the present experimental results
      provide an important clue about the Hofmeister effect on protein structure and
      present a discussion on possible alternative mechanisms.

PMID- 22462870
TI  - Statistical mechanics of coarse graining: estimating dynamical speedups from
      excess entropies.
AB  - The excess entropy of fluids has been shown to play a decisive role in the
      determination of dynamical properties [Y. Rosenfeld, Phys. Rev. A 15, 2545
      (1977)]. We argue that it could play an equally important role in connecting
      dynamical properties of atomistic and coarse-grained models of molecular fluid
      systems. Molecular dynamics simulations for an atomistic and a coarse-grained
      model of water confirm the validity of this conjecture, showing that the sizable
      enhancement of the diffusion rate upon coarse-graining is a simple function of
      the difference in the excess entropy of the two models. This empirical
      observation could ease the way to a first-principles prediction of the relation
      of dynamical properties estimated from models at different resolution.

PMID- 22462871
TI  - The origin of the conductivity maximum in molten salts. I. Bismuth chloride.
AB  - A new theory is presented to explain the conductivity maxima of molten salts
      (versus temperature and pressure). In the new theory, conductivity is due to ions
      hopping from counterion to counterion, and its temperature dependence can be
      explained with an ordinary Arrhenius equation in which the frequency prefactor A
      (for hopping opportunities) and activation energy E(a) (for hopping) are density
      dependent. The conductivity maximum is due to competing effects: as density
      decreases, the frequency of opportunities for hopping increases, but the
      probability that an opportunity is successfully hopped decreases due to rising
      E(a) caused by the increased hopping distance. The theory is successfully applied
      to molten bismuth (III) chloride, and supported by density-functional based
      molecular dynamics simulations which not only reproduce the conductivity maximum,
      but disprove the long-standing conjecture that this liquid features an
      equilibrium between BiCl(3) molecules, and BiCl(2)(+) and BiCl(4)(-) ions that
      shifts to the left with increasing temperature.

PMID- 22462872
TI  - Molecular dynamics of n-hexane: a quasi-elastic neutron scattering study on the
      bulk and spatially nanochannel-confined liquid.
AB  - We present incoherent quasi-elastic neutron scattering measurements in a wave
      vector transfer range from 0.4 A(-1) to 1.6A (-1) on liquid n-hexane confined in
      cylindrical, parallel-aligned nanochannels of 6 nm mean diameter and 260 MUm
      length in monolithic, mesoporous silicon. They are complemented with, and
      compared to, measurements on the bulk system in a temperature range from 50 K to
      250 K. The time-of-flight spectra of the bulk liquid (BL) can be modeled by
      microscopic translational as well as fast localized rotational, thermally
      excited, stochastic motions of the molecules. In the nano-confined state of the
      liquid, which was prepared by vapor condensation, we find two molecular
      populations with distinct dynamics, a fraction which is immobile on the time
      scale of 1 ps to 100 ps probed in our experiments and a second component with a
      self-diffusion dynamics slightly slower than observed for the bulk liquid. No
      hints of an anisotropy of the translational diffusion with regard to the
      orientation of the channels' long axes have been found. The immobile fraction
      amounts to about 5% at 250 K, gradually increases upon cooling and exhibits an
      abrupt increase at 160 K (20 K below bulk crystallization), which indicates pore
      freezing.

PMID- 22462873
TI  - Atomistic simulations of liquid crystal mixtures of alkoxy substituted
      phenylpyrimidines 2PhP and PhP14.
AB  - We study liquid crystal mixtures of alkoxy substituted phenylpyrimidines 2-[4
      (butyloxy)phenyl]-5-(octyloxy)pyrimidine (2PhP) and 2-[4-(tetradecyloxy)phenyl]-5
      (tetradecyloxy)pyrimidine (PhP14) using molecular dynamics simulations at the all
      atom level. The molecular length of PhP14 is 1.8 times that of 2PhP, resulting in
      an interesting binary mixture phase diagram. Our simulations are composed of 1000
      1600 molecules for a total of 80,000-130,000 atomic sites, with total simulation
      times of 60-100 ns. We first show that a pure 2PhP system self-assembles into
      isotropic, nematic, smectic A and smectic C phases, and a pure PhP14 system self
      assembles into isotropic and smectic C phases. Binary mixtures of PhP14 and 2PhP
      display a stabilization of the smectic A phase at the expense of the smectic C
      and nematic phases. We determine that the concentration-induced phase transition
      from the smectic C to the smectic A phase in the mixture is driven by an out-of
      layer fluctuation arrangement of the molecules. We also observe that the tilt
      angle in the smectic C phases formed in the mixtures is concentration dependent.
      The results of our simulations are in good agreement with the experimental
      findings of Kapernaum et al. [J. Org. Chem. 5, 65 (2009)], thus showing that
      atomistic simulations are capable of reproducing the phase behavior of liquid
      crystal mixtures and can also provide microscopic details regarding the
      mechanisms that govern phase stability.

PMID- 22462874
TI  - Modeling of an ionic liquid electrospray using molecular dynamics with
      constraints.
AB  - Molecular dynamics simulations have been performed to investigate the behavior of
      the EMIM-BF(4) ionic liquid for conditions similar to those of electrospray
      thrusters. To study the physics of ion extrusion a large system composed of
      approximately 2160 ion pairs was placed inside a platinum capillary and
      equilibrated. Diffusion coefficients and electrical conductivity were calculated
      and compared with literature values, showing good agreement and validating the
      use of a constrained dynamics model with a coarse-grained potential. An electric
      field was applied to the system in the longitudinal direction and the fraction of
      solvated and non-solvated emitted ions was analyzed. The threshold electric field
      for particle emission was found to be 1.2 V/nm, consistent with other reported
      work.

PMID- 22462875
TI  - Equation of state and jamming density for equivalent bi- and polydisperse,
      smooth, hard sphere systems.
AB  - We study bi- and polydisperse mixtures of hard sphere fluids with extreme size
      ratios up to 100. Simulation results are compared with previously found
      analytical equations of state by looking at the compressibility factor, Z, and
      agreement is found with much better than 1% deviation in the fluid regime. A
      slightly improved empirical correction to Z is proposed. When the density is
      further increased, excluded volume becomes important, but there is still a close
      relationship between many-component mixtures and their binary, two-component
      equivalents (which are defined on basis of the first three moments of the size
      distribution). Furthermore, we determine the size ratios for which the liquid
      solid transition exhibits crystalline, amorphous or mixed system structure. Near
      the jamming density, Z is independent of the size distribution and follows a -1
      power law as function of the difference from the jamming density (Z -> infinity).
      In this limit, Z depends only on one free parameter, the jamming density itself,
      as reported for several different size distributions with a wide range of widths.

PMID- 22462876
TI  - Effects of hydrogen bond and solvent polarity on the C=O stretching of bis(2
      thienyl)ketone in solution.
AB  - The optimized structural parameters, the absorption and the resonance Raman
      spectra have been investigated for the bis(2-thienyl)ketone in gas phase, in
      cyclohexane, methanol, and acetonitrile solvents by means of time dependent
      density functional theory calculations, the solvent electronic polarization
      effect on the solvation shift is examined and in well accordance with the
      calculation. The effect of increasing the polarity of the solvent is well
      represented by the polarizable continuum model, both for the absorption spectra
      and resonance Raman intensities. The Raman spectra of the C=O stretching mode,
      which is sensitive to the intermolecular interaction for bis(2-thienyl)ketone
      dissolved in solvents, were systematically studied. It was found that the
      hydrogen bond effect plays an important role in reducing the carbonyl stretching
      wavenumbers. The results of Raman shifts were interpreted through the dilution
      effect, solvation effects, and hydrogen bond-forming effects. Furthermore, the
      excitation profiles of several important Raman bands of bis(2-thienyl)ketone
      molecule in different solvents have been critically analyzed. The solvent effects
      on structural and symmetry properties of the molecule in S2 electronic state as
      well as the short-time photo relaxation dynamics have been discussed.

PMID- 22462877
TI  - Infrared absorption of CH3OSO and CD3OSO radicals produced upon photolysis of
      CH3OS(O)Cl and CD3OS(O)Cl in p-H2 matrices.
AB  - Irradiation at 239 +/- 20 nm of a p-H(2) matrix containing methoxysulfinyl
      chloride, CH(3)OS(O)Cl, at 3.2 K with filtered light from a medium-pressure
      mercury lamp produced infrared (IR) absorption lines at 3028.4 (attributable to
      nu(1), CH(2) antisymmetric stretching), 2999.5 (nu(2), CH(3) antisymmetric
      stretching), 2950.4 (nu(3), CH(3) symmetric stretching), 1465.2 (nu(4), CH(2)
      scissoring), 1452.0 (nu(5), CH(3) deformation), 1417.8 (nu(6), CH(3) umbrella),
      1165.2 (nu(7), CH(3) wagging), 1152.1 (nu(8), S=O stretching mixed with CH(3)
      rocking), 1147.8 (nu(9), S=O stretching mixed with CH(3) wagging), 989.7 (nu(10),
      C-O stretching), and 714.5 cm(-1) (nu(11), S-O stretching) modes of syn-CH(3)OSO.
      When CD(3)OS(O)Cl in a p-H(2) matrix was used, lines at 2275.9 (nu(1)), 2251.9
      (nu(2)), 2083.3 (nu(3)), 1070.3 (nu(4)), 1056.0 (nu(5)), 1085.5 (nu(6)), 1159.7
      (nu(7)), 920.1 (nu(8)), 889.0 (nu(9)), 976.9 (nu(10)), and 688.9 (nu(11)) cm(-1)
      appeared and are assigned to syn-CD(3)OSO; the mode numbers correspond to those
      used for syn-CH(3)OSO. The assignments are based on the photolytic behavior and a
      comparison of observed vibrational wavenumbers, infrared intensities, and
      deuterium isotopic shifts with those predicted with the B3P86/aug-cc-pVTZ method.
      Our results extend the previously reported four transient IR absorption bands of
      gaseous syn-CH(3)OSO near 2991, 2956, 1152, and 994 cm(-1) to 11 lines, including
      those associated with C-O, O-S, and S=O stretching modes. Vibrational wavenumbers
      of syn-CD(3)OSO are new. These results demonstrate the advantage of a diminished
      cage effect of solid p-H(2) such that the Cl atom, produced via UV
      photodissociation of CH(3)OS(O)Cl in situ, might escape from the original cage to
      yield isolated CH(3)OSO radicals.

PMID- 22462878
TI  - 2H NMR studies of glycerol dynamics in protein matrices.
AB  - We use (2)H NMR spectroscopy to investigate the rotational motion of glycerol
      molecules in matrices provided by the connective tissue proteins elastin and
      collagen. Analyzing spin-lattice relaxation, line-shape properties, and
      stimulated-echo decays, we determine the rates and geometries of the motion as a
      function of temperature and composition. It is found that embedding glycerol in
      an elastin matrix leads to a mild slowdown of glycerol reorientation at low
      temperatures and glycerol concentrations, while the effect vanishes at ambient
      temperatures or high solvent content. Furthermore, it is observed that the
      nonexponential character of the rotational correlation functions is much more
      prominent in the elastin matrix than in the bulk liquid. Results from spin
      lattice relaxation and line shape measurements indicate that, in the mixed
      systems, the strong nonexponentiality is in large part due to the existence of
      distributions of correlation times, which are broader on the long-time flank and,
      hence, more symmetric than in the neat system. Stimulated-echo analysis of slow
      glycerol dynamics reveals that, when elastin is added, the mechanism for the
      reorientation crosses over from small-angle jump dynamics to large-angle jump
      dynamics and the geometry of the motion changes from isotropic to anisotropic.
      The results are discussed against the background of present and previous findings
      for glycerol and water dynamics in various protein matrices and compared with
      observations for other dynamically highly asymmetric mixtures so as to ascertain
      in which way the viscous freezing of a fast component in the matrix of a slow
      component differs from the glassy slowdown in neat supercooled liquids.

PMID- 22462879
TI  - No fragile-to-strong crossover in LiCl-H2O solution.
AB  - Dynamics of water, especially in the temperature range of the "no man's land",
      remain a mystery. We present detailed study of dynamics in aqueous LiCl solution
      that is often considered as a model for bulk water. We employ broadband
      dielectric and light scattering spectroscopy in a broad frequency and temperature
      range. Our analysis reveals no sign of the fragile-to-strong crossover (FSC)
      neither in structural relaxation nor in translational motions. Our experimental
      results combined with a large selection of literature data lead to the clear
      conclusion-there is no FSC in dynamics of aqueous solutions at T ~ 200-230 K.
      Instead, our analysis reveals appearance of the so-called excess wing at the high
      frequency tail of the structural relaxation peak. We discuss the localized nature
      of the relaxation process that contributes to the excess wing.

PMID- 22462880
TI  - Resonant energy transfer assisted by off-diagonal coupling.
AB  - Dynamics of resonant energy transfer of a single excitation in a molecular dimer
      system are studied in the simultaneous presence of diagonal and off-diagonal
      exciton-phonon coupling. It is found that, at given temperatures, the off
      diagonal coupling can enhance both the coherence of the resonant energy transfer
      and the net quantity of energy transferred from an initially excited monomer to
      the other. Also studied is the dynamics of entanglement between the dimer system
      and the phonon bath as measured by the von Neumann entanglement entropy, and the
      inter-monomer entanglement dynamics for the excitonic system.

PMID- 22462881
TI  - Differences in first neighbor orientation behind the anomalies in the low and
      high density trans-1,2-dichloroethene liquid.
AB  - Trans-1,2-dichloroethene (HClC=CClH) has several structural and dynamic anomalies
      between its low- and high-density liquid, previously found through neutron
      scattering experiments. To explain the microscopic origin of the differences
      found in those experiments, a series of molecular dynamics simulations were
      performed. The analysis of molecular short-range order shows that the number of
      molecules in the first neighbor shell is 12 for the high-density liquid and 11
      for the low-density one. It also shows that the angular position of the center of
      mass of the first neighbor is roughly the same although the molecular orientation
      is not. In both liquids the first neighbor and its reference molecule arrange
      mainly in two configurations, each being the most probable in one of the liquids.
      First neighbors in the configuration that predominates in the high-density liquid
      tend to locate themselves closer to the reference molecule, an evidence that they
      are more strongly bonded. This arrangement facilitates a better packing of the
      rest of molecules in the first neighbor shell so that on average an additional
      molecule can be included, and is proposed to be the key in the explanation of all
      the observed anomalies in the characteristics of both liquids.

PMID- 22462882
TI  - Surface transfer doping of hydrogen-terminated diamond by C60F48: energy level
      scheme and doping efficiency.
AB  - Surface sensitive C1s core level photoelectron spectroscopy was used to examine
      the electronic properties of C(60)F(48) molecules on the C(100):H surface. An
      upward band bending of 0.74 eV in response to surface transfer doping by
      fluorofullerene molecules is measured. Two distinct molecular charge states of
      C(60)F(48) are identified and their relative concentration determined as a
      function of coverage. One corresponds to ionized molecules that participate in
      surface charge transfer and the other to neutral molecules that do not. The
      position of the lowest unoccupied molecular orbital of neutral C(60)F(48) which
      is the relevant acceptor level for transfer doping lies initially 0.6 eV below
      the valence band maximum and shifts upwards in the course of transfer doping by
      up to 0.43 eV due to a doping induced surface dipole. This upward shift in
      conjunction with the band bending determines the occupation of the acceptor level
      and limits the ultimately achievable hole concentration with C(60)F(48) as a
      surface acceptor to values close to 10(13) cm(-2) as reported in the literature.

PMID- 22462883
TI  - Electronic properties of spiro compounds for organic electronics.
AB  - The electronic properties of p-type, n-type, and ambipolar spiro materials have
      been investigated using a combination of photoemission spectroscopy, electron
      energy-loss spectroscopy, and density functional based calculations. Our results
      provide insight into the occupied density of states as well as the electronic
      excitation spectra. Comparison of experimental and theoretical data allows the
      identification of the orbitals responsible for charge transport and optical
      properties.

PMID- 22462885
TI  - Physical basis for constrained lattice density functional theory.
AB  - To study nucleation phenomena in an open system, a constrained lattice density
      functional theory (LDFT) method has been developed before to identify the
      unstable directions of grand potential functional and to stabilize nuclei by
      imposing a suitable constraint. In this work, we answer several questions about
      the method on a fundamental level, and give a firmer basis for the constrained
      LDFT method. First, we demonstrate that the nucleus structure and free energy
      barrier from a volume constraint method are equivalent to those from a surface
      constraint method. Then, we show that for the critical nucleus, the constrained
      LDFT method in fact produces a bias-free solution for both the nucleus structure
      and nucleation barrier. Finally, we give a physical interpretation of the
      Lagrange multiplier in the constraint method, which provides the generalized
      force to stabilize a nucleus in an open system. The Lagrange multiplier is found
      to consist of two parts: part I of the constraint produces an effective pressure,
      and part II imposes a constraint to counteract the supersaturation.

PMID- 22462884
TI  - Helium mediated deposition: modeling the He-TiO2(110)-(1*1) interaction potential
      and application to the collision of a helium droplet from density functional
      calculations.
AB  - This paper is the first of a two-part series dealing with quantum-mechanical
      (density-functional-based) studies of helium-mediated deposition of catalytic
      species on the rutile TiO(2)(110)-(1*1) surface. The interaction of helium with
      the TiO(2)(110)-(1*1) surface is first evaluated using the Perdew-Burke-Ernzerhof
      functional at a numerical grid dense enough to build an analytical three
      dimensional potential energy surface. Three (two prototype) potential models for
      the He-surface interaction in helium scattering calculations are analyzed to
      build the analytical potential energy surface: (1) the hard-corrugated-wall
      potential model; (2) the corrugated-Morse potential model; and (3) the three
      dimensional Morse potential model. Different model potentials are then used to
      study the dynamics upon collision of a (4)He(300) cluster with the TiO(2)(110)
      surface at zero temperature within the framework of a time-dependent density
      functional approach for the quantum fluid [D. Mateo, D. Jin, M. Barranco, and M.
      Pi, J. Chem. Phys. 134, 044507 (2011)] and classical dynamics calculations. The
      laterally averaged density functional theory-based potential with an added long
      range dispersion interaction term is further applied. At variance with classical
      dynamics calculations, showing helium droplet splashing out of the surface at
      impact, the time evolution of the macroscopic helium wave-function predicts that
      the helium droplet spreads on the rutile surface and leads to the formation of a
      thin film above the substrate. This work thus provides a basis for simulating
      helium mediated deposition of metallic clusters embedded within helium
      nanodroplets.

PMID- 22462886
TI  - Rippled nanocarbons from periodic arrangements of reordered bivacancies in
      graphene or nanotubes.
AB  - We report on various nanocarbons formed from a unique structural pattern
      containing two pentagons, three hexagons, and two heptagons, resulting from local
      rearrangements around a divacancy in pristine graphene, or nanotubes. This defect
      can be inserted in sheets or tubes either individually or as extended defect
      lines. Sheets or tubes containing only this defect as a pattern can also be
      obtained. These fully defective sheets, and most of the tubes, present a very
      pronounced rippled (wavy) structure and their energies are lower than other
      structures based on pentagons and heptagons published so far. Another
      particularity of these rippled carbon sheets is their ability to fold themselves
      into a two-dimensional porous network of interconnected tubes upon heat treatment
      as shown by hybrid Monte Carlo simulations. Finally, contrary to the common
      belief that pentagon/heptagon based structures are metallic, this work shows that
      this defect pattern should give rise to semimetallic conduction.

PMID- 22462887
TI  - Studies of structural, dynamical, and interfacial properties of 1-alkyl-3
      methylimidazolium iodide ionic liquids by molecular dynamics simulation.
AB  - Bulk and surface properties of the ionic liquids 1-alkyl-3-methyl-imidazolium
      iodides ([C(n)mim]I) were simulated by classical molecular dynamics using all
      atom non-polarizable force field (n = 4, butyl; 6, hexyl; 8, octyl). The
      structure of ionic liquids were initially optimized by density functional theory
      and atomic charges obtained by CHELPG method. Reduction of partial atomic charges
      (by 20% for simulation of density and surface tension, and by 10% for viscosity)
      found to improve the accuracy, while a non-polarizable force field was applied.
      Additionally, the simulation ensembles approach the equilibrium faster when the
      charge reduction is applied. By these refined force field parameters, simulated
      surface tensions in the range of 323-393 k are quite in agreement with the
      experiments. Simulation of temperature dependent surface tension of [C(4)mim]I
      well beyond room temperature (up to 700 K) permits prediction of the critical
      temperature in agreement with that predicted from experimental surface tension
      data. Simulated densities in the range of 298-450 K for the three ionic liquids
      are within 0.8% of the experimental data. Structural properties for [C(4)mim]I
      were found to be in agreement with the results of Car-Parrinello molecular
      dynamics simulation we performed, which indicates a rather well-structured cation
      anion interaction and occurs essentially through the imidazolium ring cation.
      Diffusion coefficient changes with alkyl chain length in the order of [C(8)mim]I
      > [C(6)mim]I > [C(4)mim]I for the cation and the anion. Formation of a dense
      domain in subsurface region is quite evident, and progressively becomes denser as
      the alkyl chain length increases. Bivariate orientational analysis was used to
      determine the average orientation of molecule in ionic liquids surface,
      subsurface, and bulk regions. Dynamic bisector-wise and side-wise movement of the
      imodazolium ring cation in the surface region can be deduced from the bivariate
      maps. Atom-atom density profile and bivariate analysis indicate that the
      imidazolium cation takes a spoon like configuration in the surface region and the
      tilt of alkyl group is a function length of alkyl chain exposing as linear as
      possible to the vapor phase.

PMID- 22462888
TI  - The source of the Ti 3d defect state in the band gap of rutile titania (110)
      surfaces.
AB  - The origin of the Ti 3d defect state seen in the band gap for reduced rutile
      TiO(2)(110) surfaces has been excitingly debated. The probable candidates are
      bridging O vacancies (V(O)) and Ti interstitials (Ti-int) condensed near the
      surfaces. The aim of this study is to give insights into the source of the gap
      state via photoelectron spectroscopy combined with ion scattering and elastic
      recoil detection analyses. We have made three important findings: (i) The
      intensity of the gap state observed is well correlated with the sheet resistance
      measured with a 4-point probe, inversely proportional to the density of Ti-int.
      (ii) Sputter/annealing cycles in ultrahigh vacuum (UHV) lead to efficient V(O)
      creation and condensation of Ti-int near the surface, while only annealing below
      870 K in UHV condenses subsurface Ti-int but does not create V(O) significantly.
      (iii) The electronic charge to heal a V(O) is almost twice that to create an O
      adatom adsorbed on the 5-fold Ti row. The results obtained here indicate that
      both the V(O) and Ti-interstitials condensed near the surface region contribute
      to the gap state and the contribution to the gap state from the Ti-int becomes
      comparable to that from V(O) for the substrates with low sheet resistance less
      than ~200 Omega/square.

PMID- 22462889
TI  - Molecular dynamics simulation study of solvent effects on conformation and
      dynamics of polyethylene oxide and polypropylene oxide chains in water and in
      common organic solvents.
AB  - In this paper, the conformation and dynamics properties of polyethylene oxide
      (PEO) and polypropylene oxide (PPO) polymer chains at 298 K have been studied in
      the melt and at infinite dilution condition in water, methanol, chloroform,
      carbon tetrachloride, and n-heptane using molecular dynamics simulations. The
      calculated density of PEO melt with chain lengths of n = 2, 3, 4, 5 and, for PPO,
      n = 7 are in good agreement with the available experimental data. The
      conformational properties of PEO and PPO show an increasing gauche preference for
      the O-C-C-O dihedral in the following order water>methanol>chloroform>carbon
      tetrachloride = n-heptane. On the contrary, the preference for trans conformation
      has a maximum in carbon tetrachloride and n-heptane followed in the order by
      chloroform, methanol, and water. The PEO conformational preferences are in
      qualitative agreement with results of NMR studies. PEO chains formed different
      types of hydrogen bonds with polar solvent molecules. In particular, the
      occurrence of bifurcated hydrogen bonding in chloroform was also observed. Radii
      of gyration of PEO chains of length larger than n = 9 monomers showed a good
      agreement with light scattering data in water and in methanol. For the shorter
      chains the observed deviations are probably due to the enhanced hydrophobic
      effects caused by the terminal methyl groups. For PEO the fitting of end-to-end
      distance distributions with the semi-flexible chain model at 298 K provided
      persistence lengths of 0.375 and 0.387 nm in water and methanol, respectively.
      Finally, the radius of gyration of Pluronic P85 turned out to be 2.25 +/- 0.4 nm
      at 293 K in water in agreement with experimental data.

PMID- 22462890
TI  - Shear viscosity of inhomogeneous fluids.
AB  - Using molecular dynamics simulations on inhomogeneous fluids, we have studied the
      effects of strong density inhomogeneities of varying wavelengths on the shear
      viscosity computed locally. For dense fluids, the local average density model
      combined with an adequate weight function yields a good description of the
      viscosity profiles obtained by simulations. However, for low density
      inhomogeneous fluids, the local average density model is unable to describe
      correctly the viscosity profiles obtained by simulations. It is shown that this
      weakness can be overcome by taking into account the density inhomogeneity in the
      local translational contribution to the viscosity using a density gradient like
      approach.

PMID- 22462891
TI  - Ion condensation behavior and dynamics of water molecules surrounding the sodium
      poly(methacrylic acid) chain in water: a molecular dynamics study.
AB  - All-atom molecular dynamics simulations are used to study the condensation
      behavior of monovalent (Na(+)) and multivalent (Ca(2+)) salt counterions
      associated with the co-ions (Cl(-)) surrounding the charged poly(methacrylic
      acid) (PMAA) chain in water. The study is extended to the influences on chain
      conformation, local arrangement, and dynamics of water in the highly diluted
      aqueous solutions. We find that even when the salt ions are monovalent, they
      attract more than one charged monomer and act as a bridging agent within the
      chain, as the multivalent salt ions. In principle, the salt ions bridge between
      not only the "non-adjacent" but also the "adjacent" charged monomers, leading to
      a more coil-like and a locally stretched conformation, respectively. With an
      increase in the salt concentration, the amount of coiled-type condensed ions
      increase and reach a maximum when the chain conformation becomes the most
      collapsed; whereas, the stretched-type shows an opposite trend. Our results show
      that the attractive interactions through the condensed salt ions between the non
      adjacent monomers are responsible for the conformational collapse. When the salt
      concentration increases high enough, a significant increase for the stretched
      type condensed ions makes an expansion effect on the chain. These stretched-type
      salt ions, followed by the adsorption of the co-ions and water molecules, tend to
      form a multilayer organization outside surrounding the PMAA chain. Thus, the
      expansion degree of the chain conformation is greatly limited. When only the
      monovalent Na(+) ions are present in the solutions, water molecules are primarily
      adsorbed into either the condensed Na(+) ions or the COO(-) groups. These
      adsorbed water molecules form hydrogen bonds with each other and enhance the
      local bridging behavior associated with the Na(+) condensation on the resultant
      chain conformation. With an increase in the amount of multivalent Ca(2+) salt
      ions, more water molecules are bonded directly with the condensed Ca(2+) ions. In
      this case, only the condensed Ca(2+) ions provide a strong bridging effect within
      the polymer chain. We observe a significant shift towards a higher frequency of
      the oxygen vibration spectrum and only a slight shift towards a higher frequency
      of the hydrogen spectrum for the water molecules associated with the ion
      condensation.

PMID- 22462892
TI  - Generalized Flory-Huggins theory-based equation of state for ring and chain
      fluids.
AB  - By modeling the ring-like molecule as a pearl necklace of freely jointed hard
      sphere, we develop a new equation of state (EOS) for the ring-like fluids on the
      basis of generalized Flory-Huggins (GFH) theory. Before proposing the new EOS of
      the ring-like fluids, we first modify the generalized Flory-Huggins theory for
      the chain fluids by incorporating a function related to the packing fraction into
      the insertion probability. The results indicate that the modified GFH EOS can
      predict the compressibility factors more accurately than the GFH EOS, especially
      for the intermediate and high packing fractions (eta >= 0.157). Subsequently, the
      modified GFH theory-based EOS for the ring-like fluids is proposed. Compared to
      the Monte Carlo data of 3-mer, 4-mer, 5-mer, 6-mer, 16-mer, and 32-mer ring-like
      fluids, our EOS exhibits the best prediction among four EOSs for the
      compressibility factors at intermediate and high packing fractions (eta >=
      0.157), although our EOS also shows a slight underestimation for the
      compressibility factors at low packing fractions. In summary, this is the first
      report on the generalized Flory-Huggins theory-based EOS for the ring-like
      fluids. It is expected that the same strategy can be applied to these fluids with
      more complex architectures.

PMID- 22462893
TI  - Origin of de-swelling and dynamics of dense ionic microgel suspensions.
AB  - A direct consequence of the finite compressibility of a swollen microgel is that
      it can shrink and deform in response to an external perturbation. As a result,
      concentrated suspensions of these particles exhibit relaxation dynamics and
      rheological properties which can be very different with respect to those of a
      hard sphere suspension or an emulsion. We study the reduction in size of ionic
      microgels in response to increasing number of particles to show that particle
      shrinkage originates primarily from steric compression, and that the effect of
      ion-induced de-swelling of the polymer network is negligible. With increasing
      particle concentration, the single particle dynamics switch from those typical of
      a liquid to those of a super-cooled liquid and finally to those of a glass.
      However, the transitions occur at volume fractions much higher than those
      characterizing a hard sphere system. In the super-cooled state, the distribution
      of displacements is non-gaussian and the dependence of the structural relaxation
      time on volume fraction is describable by a Volger-Fulcher-Tammann function.

PMID- 22462894
TI  - Nanostructures and phase diagrams of ABC star triblock copolymers in pore
      geometries.
AB  - The nanostructures and phase diagrams of ABC star triblock copolymers in pore
      geometries are investigated using the real-space self-consistent field theory in
      two-dimensional space. Two types of pores with neutral surfaces, namely, pores
      with small and large diameters, are considered. A rich variety of nanostructures
      are exhibited by the ABC star triblock copolymers in these two types of pores,
      which differ from those observed in bulk and in other confinements. These
      structures include perpendicular undulating lamellae, concentric core-shell
      cylinders, polygonal tiling with cylindrical arrangements, and other complex
      structures. Triangular phase diagrams for the ABC star triblock copolymers are
      constructed. The small pores clearly affect the corner and central space of the
      phase diagrams by distorting the bulk structures into concentric arrangements.
      Meanwhile, the large pores induce the transformation of bulk structures into
      concentric structures in most of the phase space, but slightly affect the
      structures at the center of the phase diagrams. Furthermore, the order-order and
      order-disorder phase transitions, as well as the stable and metastable phases, in
      the triangular phase diagrams are examined by analyzing their free energies.
      These observations on the ABC star triblock copolymers in the pore geometries
      provide a deeper insight into the behavior of macromolecules in a confined
      system.

PMID- 22462895
TI  - Sheared polymer glass and the question of mechanical rejuvenation.
AB  - There has been much recent debate as to whether mechanical deformation reverses
      the aging of a material, and returns it to a structure characteristic of the
      system at a higher temperature. We use molecular dynamics simulation to address
      this problem by carrying out shear and temperature increase simulation on atactic
      glassy polystyrene. Our results show explicitly that the structure (as quantified
      by the torsion population) changes associated with shear and temperature increase
      are quantitatively--and in some cases qualitatively--different. This is due to
      the competition between rejuvenation and physical aging, and we show this by
      carrying out a relaxation simulation. The conclusion agrees with those from
      previous experiments and simulations, which were suggestive of mechanical
      deformation moving the system to structures distinct from those reached during
      thermal treatment.

PMID- 22462896
TI  - How to accelerate protein search on DNA: location and dissociation.
AB  - One of the most important features of biological systems that controls their
      functioning is the ability of protein molecules to find and recognize quickly
      specific target sites on DNA. Although these phenomena have been studied
      extensively, detailed mechanisms of protein-DNA interactions during the search
      are still not well understood. Experiments suggest that proteins typically find
      their targets fast by combining three-dimensional and one-dimensional motions,
      and most of the searching time proteins are non-specifically bound to DNA.
      However these observations are surprising since proteins diffuse very slowly on
      DNA, and it seems that the observed fast search cannot be achieved under these
      conditions for single proteins. Here we propose two simple mechanisms that might
      explain some of these controversial observations. Using first-passage time
      analysis, it is shown explicitly that the search can be accelerated by changing
      the location of the target and by effectively irreversible dissociations of
      proteins. Our theoretical predictions are supported by Monte Carlo computer
      simulations.

PMID- 22462897
TI  - Do we have to explicitly model the ions in brownian dynamics simulations of
      proteins?
AB  - Brownian dynamics (BD) is a very efficient coarse-grained simulation technique
      which is based on Einstein's explanation of the diffusion of colloidal particles.
      On these length scales well beyond the solvent granularity, a treatment of the
      electrostatic interactions on a Debye-Huckel (DH) level with its continuous ion
      densities is consistent with the implicit solvent of BD. On the other hand, since
      many years BD is being used as a workhorse simulation technique for the much
      smaller biological proteins. Here, the assumption of a continuous ion density,
      and therefore the validity of the DH electrostatics, becomes questionable. We
      therefore investigated for a few simple cases how far the efficient DH
      electrostatics with point charges can be used and when the ions should be
      included explicitly in the BD simulation. We find that for large many-protein
      scenarios or for binary association rates, the conventional continuum methods
      work well and that the ions should be included explicitly when detailed
      association trajectories or protein folding are investigated.

PMID- 22462899
TI  - Invited article: A materials investigation of a phase-change micro-valve for
      greenhouse gas collection and other potential applications.
AB  - The deleterious consequences of climate change are well documented. Future
      climate treaties might mandate greenhouse gas (GHG) emissions measurement from
      signatories in order to verify compliance. The acquisition of atmospheric
      chemistry would benefit from low cost, small size/weight/power of microsystems.
      In this paper, we investigated several key materials science aspects of a phase
      change microvalve (PCMUV) technology with low power/size/weight/cost for
      ubiquitous GHG sampling. The novel design, based on phase-change material low
      melting-point eutectic metal alloys (indium-bismuth, InBi and tin-lead, SnPb),
      could be actuated at temperatures as low as 72  degrees C. Valve manufacturing
      was based on standard thick and thin-film processes and solder technologies that
      are commonly used in industry, enabling low-cost, high-volume fabrication. Aging
      studies showed that it was feasible to batch fabricate the PCMUVs and store them
      for future use, especially in the case of SnPb alloys. Hermetic sealing of the
      valve prototypes was demonstrated through helium leak testing, and Mil spec leak
      rates less than 1 * 10(-9) atm cm(3)/s were achieved. This confirms that the
      sample capture and analysis interval can be greatly expanded, easing the
      logistical burdens of ubiquitous GHG monitoring. Highly conservative and
      hypothetical CO(2) bias due to valve actuation at altitude in 1 cm(3)
      microsamplers would be significantly below 1.0 and 2.2 ppmv for heat-treated InBi
      and SnPb solders, respectively. The CO(2) bias from the PCMUV scales well, as a
      doubling of sampler volume halved the bias. We estimated the shelf life of the
      SnPb PCMUVs to be at least 2.8 years. These efforts will enable the development
      of low cost, low dead volume, small size/weight microsystems for monitoring GHGs
      and volatile organic compounds.

PMID- 22462900
TI  - Stark spectroscopy of a probe lithium beam excited with two dye lasers as a
      technique to study a high-power ion-beam diode.
AB  - A non-disturbing measurement of electric field distributions is a subject of
      special interest in plasma physics and high-voltage devices. In this paper we
      describe a diagnostic technique for remote sensing of electric fields via
      injection of a probe beam of lithium atoms and cascade excitation of resonance
      fluorescence with two broadband dye lasers. The fluorescence spectrum was
      recorded using a monochromator equipped with an optical multi-channel analyser.
      The magnitude of the local electric field was retrieved from the Stark-shifted
      components of the 3d-2p lithium spectral line. The technique was applied to
      measurements of the electric field in the applied-B-field high-voltage diode of
      the 1 TW KALIF ion-beam accelerator.

PMID- 22462901
TI  - Measurements of electron density and temperature in the H-1 heliac plasma by
      helium line intensity ratios.
AB  - Electron density and temperature distributions in the H-1 heliac plasma are
      measured using the helium line intensity ratio technique based on a collisional
      radiative model. An inversion approach with minimum Fisher regularization is
      developed to reconstruct the ratios of the local emission radiances from detected
      line-integrated intensities. The electron density and temperature inferred from
      the He I 667.8/728.1 and He I 728.1/706.5 nm line ratios are in good agreement
      with those from other diagnostic techniques in the inner region of the plasma.
      The electron density and temperature values appear to be a little high in the
      outer region of the plasma. Some possible causes of the discrepancy in the outer
      region are discussed.

PMID- 22462902
TI  - Terahertz time domain attenuated total reflection spectroscopy with an integrated
      prism system.
AB  - We demonstrated attenuated total reflection (ATR) spectroscopy with an integrated
      prism system that included a terahertz emitter, a terahertz receiver, and an ATR
      prism. The ATR prism had two internal off-axis parabolic mirrors for,
      respectively, collimating and focusing the terahertz waves. The Fresnel loss at
      each interface was reduced, and the total propagation efficiency was 3.36 times
      larger than when using a non-integrated prism system. The refractive index of
      water samples calculated from the experimental data showed good agreement with
      values reported in the literature.

PMID- 22462903
TI  - Custom single-photon avalanche diode with integrated front-end for parallel
      photon timing applications.
AB  - Emerged as a solid state alternative to photo multiplier tubes (PMTs), single
      photon avalanche diodes (SPADs) are nowadays widely used in the field of single
      photon timing applications. Custom technology SPADs assure remarkable
      performance, in particular a 10 counts/s dark count rate (DCR) at low
      temperature, a high photon detection efficiency (PDE) with a 50% peak at 550 nm
      and a 30 ps (full width at half maximum, FWHM) temporal resolution, even with
      large area devices, have been obtained. Over the past few years, the birth of
      novel techniques of analysis has led to the parallelization of the measurement
      systems and to a consequent increasing demand for the development of monolithic
      arrays of detectors. Unfortunately, the implementation of a multidimensional
      system is a challenging task from the electrical point of view; in particular,
      the avalanche current pick-up circuit, used to obtain the previously reported
      performance, has to be modified in order to enable high parallel temporal
      resolution, while minimizing the electrical crosstalk probability between
      channels. In the past, the problem has been solved by integrating the front-end
      electronics next to the photodetector, in order to reduce the parasitic
      capacitances and consequently the filtering action on the current signal of the
      SPAD, leading to an improvement of the timing jitter at higher threshold. This
      solution has been implemented by using standard complementary metal-oxide
      semiconductor (CMOS) technologies, which, however, do not allow a complete
      control on the SPAD structure; for this reason the intrinsic performance of CMOS
      SPADs, such as DCR, PDE, and afterpulsing probability, are worse than those
      attainable with custom detectors. In this paper, we propose a pixel architecture,
      which enables the development of custom SPAD arrays in which every channel
      maintains the performance of the best single photodetector. The system relies on
      the integration of the timing signal pick-up circuit next to the photodiode,
      achieved by modifying the technological process flow used for the fabrication of
      the custom SPAD. The pixel is completed by an external standard CMOS active
      quenching circuit, which assures stable timing performance at quite high count
      rate (>1 MHz).

PMID- 22462904
TI  - A technique for contactless measurement of water temperature using Stokes and
      anti-Stokes comparative Raman spectroscopy.
AB  - Contactless measurements of water temperature are utilized in a number of
      sciences, such as oceanography, climatology, and biology. Previously reported
      Raman spectroscopy techniques exploited the changes in the shapes of water Raman
      bands. Interpretation of these changes is difficult since these bands are
      composed of multiple lines, each influenced not only by temperature but also by
      pressure and salinity. This paper presents a proof-of-principal demonstration of
      a contactless technique which determines water temperature from the ratio of
      Stokes and anti-Stokes intensities of the water 180 cm(-1) Raman band. This ratio
      is not sensitive to pressure and salinity, allowing reliable determination of
      water temperature.

PMID- 22462905
TI  - Fabrication of microgrooves on a curved surface by the confocal measurement
      system using pulse laser and continuous laser.
AB  - In order to fabricate microgrooves on a curved surface, the curved surface was
      measured with a confocal system and then it was used for laser microprocessing.
      This paper proposes a new method of using a pulse laser for the confocal system
      to measure the curved surface. It also compares the conventional way of using a
      continuous laser and a new way of using the pulse laser with the confocal system.
      Using the data measured with the pulse laser for fabrication, microgrooves were
      fabricated on a curved surface. The width of the fabricated microgroove was 10
      MUm and the depth was 27 MUm. The microgroove fabricated on a curved surface as a
      part of this study can be used in injection molding to manufacture a
      micropatterned plastic surface at a low cost. This plastic surface can be applied
      for a superhydrophobic surface, a self-cleaning surface, or a biochip.

PMID- 22462906
TI  - A spherical crystal imager for OMEGA EP.
AB  - A narrowband x ray imager for the Cu K(alpha) line at ~8 keV using a spherically
      bent quartz crystal has been implemented on the OMEGA EP laser at the University
      of Rochester. The quartz crystal is cut along the 2131 (211) planes for a 2d
      spacing of 0.3082 nm, resulting in a Bragg angle of 88.7 degrees , very close to
      normal incidence. An optical system is used to remotely align the spherical
      crystal without breaking the vacuum of the target chamber. The images show a high
      signal-to-background ratio of typically >100:1 with laser energies >=1 kJ at a 10
      ps pulse duration and a spatial resolution of less than 10 MUm.

PMID- 22462907
TI  - A wireless handheld probe with spectrally constrained evolution strategies for
      diffuse optical imaging of tissue.
AB  - We present a low-cost, portable, wireless diffuse optical imaging device. The
      handheld device is fast, portable, and can be applied to a wide range of both
      static and dynamic imaging applications including breast cancer, functional brain
      imaging, and peripheral artery disease. The continuous-wave probe has four near
      infrared wavelengths and uses digital detection techniques to perform
      measurements at 2.3 Hz. Using a multispectral evolution algorithm for chromophore
      reconstruction, we can measure absolute oxygenated and deoxygenated hemoglobin
      concentration as well as scattering in tissue. Performance of the device is
      demonstrated using a series of liquid phantoms comprised of Intralipid((r)), ink,
      and dye.

PMID- 22462908
TI  - Thermal effects in the Input Optics of the Enhanced Laser Interferometer
      Gravitational-Wave Observatory interferometers.
AB  - We present the design and performance of the LIGO Input Optics subsystem as
      implemented for the sixth science run of the LIGO interferometers. The Initial
      LIGO Input Optics experienced thermal side effects when operating with 7 W input
      power. We designed, built, and implemented improved versions of the Input Optics
      for Enhanced LIGO, an incremental upgrade to the Initial LIGO interferometers,
      designed to run with 30 W input power. At four times the power of Initial LIGO,
      the Enhanced LIGO Input Optics demonstrated improved performance including better
      optical isolation, less thermal drift, minimal thermal lensing, and higher
      optical efficiency. The success of the Input Optics design fosters confidence for
      its ability to perform well in Advanced LIGO.

PMID- 22462909
TI  - Spatial and spectral performance of a chromotomosynthetic hyperspectral imaging
      system.
AB  - The spatial and spectral resolutions achievable by a prototype rotating prism
      chromotomosynthetic imaging (CTI) system operating in the visible spectrum are
      described. The instrument creates hyperspectral imagery by collecting a set of 2D
      images with each spectrally projected at a different rotation angle of the prism.
      Mathematical reconstruction techniques that have been well tested in the field of
      medical physics are used to reconstruct the data to produce the 3D hyperspectral
      image. The instrument operates with a 100 mm focusing lens in the spectral range
      of 400-900 nm with a field of view of 71.6 mrad and angular resolution of 0.8-1.6
      MUrad. The spectral resolution is 0.6 nm at the shortest wavelengths, degrading
      to over 10 nm at the longest wavelengths. Measurements using a point-like target
      show that performance is limited by chromatic aberration. The system model is
      slightly inaccurate due to poor estimation of detector spatial resolution, this
      is corrected based on results improving model performance. As with traditional
      dispersion technology, calibration of the transformed wavelength axis is
      required, though with this technology calibration improves both spectral and
      spatial resolution. While this prototype does not operate at high speeds,
      components exist which will allow for CTI systems to generate hyperspectral video
      imagery at rates greater than 100 Hz.

PMID- 22462910
TI  - Direct measurement of the spectral transfer function of a laser based anemometer.
AB  - The effect of a continuous-wave (cw) laser based anemometer's probe volume on the
      measurement of wind turbulence is studied in this paper. Wind speed time series
      acquired by both a remote sensing cw laser anemometer, whose line-of-sight was
      aligned with the wind direction, and by a reference sensor (sonic anemometer)
      located in the same direction, were used. The spectral transfer function, which
      describes the attenuation of the power spectral density of the wind speed
      turbulence, was calculated and found to be in good agreement with the theoretical
      exponential function, which is based on the properties of the probe volume of a
      focused Gaussian laser beam. Parameters such as fluctuations of the wind
      direction, as well as the overestimation of the laser Doppler spectrum threshold,
      were found to affect the calculation of the spectral transfer function by
      introducing high frequency noise.

PMID- 22462911
TI  - Design and evaluation of an imaging spectrophotometer incorporating a uniform
      light source.
AB  - Accounting for light that is diffusely scattered from a surface is one of the
      practical challenges in reflectance measurement. Integrating spheres are commonly
      used for this purpose in point measurements of reflectance and transmittance.
      This solution is not directly applicable to a spectral imaging application for
      which diffuse reflectance measurements are desired. In this paper, an imaging
      spectrophotometer design is presented that employs a uniform light source to
      provide diffuse illumination. This creates the inverse measurement geometry to
      the directional illumination/diffuse reflectance mode typically used for point
      measurements. The final system had a spectral range between 400 and 1000 nm with
      a 5.2 nm resolution, a field of view of approximately 0.5 m by 0.5 m, and
      millimeter spatial resolution. Testing results indicate illumination uniformity
      typically exceeding 95% and reflectance precision better than 1.7%.

PMID- 22462912
TI  - Design and performance of a versatile curved-crystal spectrometer for high
      resolution spectroscopy in the tender x-ray range.
AB  - A complete in-vacuum curved-crystal x-ray emission spectrometer in Johansson
      geometry has been constructed for a 2-6 keV energy range with sub natural line
      width energy resolution. The spectrometer is designed to measure x-ray emission
      induced by photon and charged particle impact on solid and gaseous targets. It
      works with a relatively large x-ray source placed inside the Rowland circle and
      employs position sensitive detection of diffracted x-rays. Its compact modular
      design enables fast and easy installation at a synchrotron or particle
      accelerator beamline. The paper presents main characteristics of the spectrometer
      and illustrates its capabilities by showing few selected experimental examples.

PMID- 22462913
TI  - Effect of source tuning parameters on the plasma potential of heavy ions in the
      18 GHz high temperature superconducting electron cyclotron resonance ion source.
AB  - Plasma potentials for various heavy ions have been measured using the retarding
      field technique in the 18 GHz high temperature superconducting ECR ion source,
      PKDELIS [C. Bieth, S. Kantas, P. Sortais, D. Kanjilal, G. Rodrigues, S. Milward,
      S. Harrison, and R. McMahon, Nucl. Instrum. Methods B 235, 498 (2005); D.
      Kanjilal, G. Rodrigues, P. Kumar, A. Mandal, A. Roy, C. Bieth, S. Kantas, and P.
      Sortais, Rev. Sci. Instrum. 77, 03A317 (2006)]. The ion beam extracted from the
      source is decelerated close to the location of a mesh which is polarized to the
      source potential and beams having different plasma potentials are measured on a
      Faraday cup located downstream of the mesh. The influence of various source
      parameters, viz., RF power, gas pressure, magnetic field, negative dc bias, and
      gas mixing on the plasma potential is studied. The study helped to find an upper
      limit of the energy spread of the heavy ions, which can influence the design of
      the longitudinal optics of the high current injector being developed at the Inter
      University Accelerator Centre. It is observed that the plasma potentials are
      decreasing for increasing charge states and a mass effect is clearly observed for
      the ions with similar operating gas pressures. In the case of gas mixing, it is
      observed that the plasma potential minimizes at an optimum value of the gas
      pressure of the mixing gas and the mean charge state maximizes at this value.
      Details of the measurements carried out as a function of various source
      parameters and its impact on the longitudinal optics are presented.

PMID- 22462914
TI  - Lifetime measurements in an electrostatic ion beam trap using image charge
      monitoring.
AB  - A technique for mass-selective lifetime measurements of keV ions in a linear
      electrostatic ion beam trap is presented. The technique is based on bunching the
      ions using a weak RF potential and non-destructive ion detection by a pick-up
      electrode. This method has no mass-limitation, possesses the advantage of
      inherent mass-selectivity, and offers a possibility of measuring simultaneously
      the lifetimes of different ion species with no need for prior mass-selection.

PMID- 22462916
TI  - Surface thermocouples for measurement of pulsed heat flux in the divertor of the
      Alcator C-Mod tokamak.
AB  - A novel set of thermocouple sensors has been developed to measure heat fluxes
      arriving at divertor surfaces in the Alcator C-Mod tokamak, a magnetic
      confinement fusion experiment. These sensors operate in direct contact with the
      divertor plasma, which deposits heat fluxes in excess of ~10 MW/m(2) over an ~1 s
      pulse. Thermoelectric EMF signals are produced across a non-standard bimetallic
      junction: a 50 MUm thick 74% tungsten-26% rhenium ribbon embedded in a 6.35 mm
      diameter molybdenum cylinder. The unique coaxial geometry of the sensor combined
      with its single-point electrical ground contact minimizes interference from the
      plasma/magnetic environment. Incident heat fluxes are inferred from surface
      temperature evolution via a 1D thermal heat transport model. For an incident heat
      flux of 10 MW/m(2), surface temperatures rise ~1000  degrees C/s, corresponding
      to a heat flux flowing along the local magnetic field of ~200 MW/m(2). Separate
      calorimeter sensors are used to independently confirm the derived heat fluxes by
      comparing total energies deposited during a plasma pulse. Langmuir probes in
      close proximity to the surface thermocouples are used to test plasma-sheath heat
      transmission theory and to identify potential sources of discrepancies among
      physical models.

PMID- 22462915
TI  - The geometric factor of electrostatic plasma analyzers: a case study from the
      Fast Plasma Investigation for the Magnetospheric Multiscale mission.
AB  - We report our findings comparing the geometric factor (GF) as determined from
      simulations and laboratory measurements of the new Dual Electron Spectrometer
      (DES) being developed at NASA Goddard Space Flight Center as part of the Fast
      Plasma Investigation on NASA's Magnetospheric Multiscale mission. Particle
      simulations are increasingly playing an essential role in the design and
      calibration of electrostatic analyzers, facilitating the identification and
      mitigation of the many sources of systematic error present in laboratory
      calibration. While equations for laboratory measurement of the GF have been
      described in the literature, these are not directly applicable to simulation
      since the two are carried out under substantially different assumptions and
      conditions, making direct comparison very challenging. Starting from first
      principles, we derive generalized expressions for the determination of the GF in
      simulation and laboratory, and discuss how we have estimated errors in both
      cases. Finally, we apply these equations to the new DES instrument and show that
      the results agree within errors. Thus we show that the techniques presented here
      will produce consistent results between laboratory and simulation, and present
      the first description of the performance of the new DES instrument in the
      literature.

PMID- 22462917
TI  - Development of the large neutron imaging system for inertial confinement fusion
      experiments.
AB  - Inertial confinement fusion (ICF) requires a high resolution (~10 MUm) neutron
      imaging system to observe deuterium and tritium (DT) core implosion asymmetries.
      A new large (150 mm entrance diameter: scaled for Laser MegaJoule [P. A.
      Holstein, F. Chaland, C. Charpin, J. M. Dufour, H. Dumont, J. Giorla, L. Hallo,
      S. Laffite, G. Malinie, Y. Saillard, G. Schurtz, M. Vandenboomgaerde, and F.
      Wagon, Laser and Particle Beams 17, 403 (1999)]) neutron imaging detector has
      been developed for such ICF experiments. The detector has been fully
      characterized using a linear accelerator and a (60)Co gamma-ray source. A
      penumbral aperture was used to observe DT-gas-filled target implosions performed
      on the OMEGA laser facility. [T. R. Boehly, D. L. Brown, R. S. Craxton, R. L.
      Keck, J. P. Knauer, J. H. Kelly, T. J. Kessler, S. A. Kumpan, S. J. Loucks, S. A.
      Letzring, F. J. Marshall, R. L. McCrory, S. F. B. Morse, W. Seka, J. M. Soures,
      and C. P. Verdon, Opt. Commun. 133, 495 (1997)] Neutron core images of 14 MeV
      with a resolution of 15 MUm were obtained and are compared to x-ray images of
      comparable resolution.

PMID- 22462918
TI  - A real-time velocity diagnostic for NSTX.
AB  - A new system for fast measurements of the plasma toroidal velocity has been
      installed on the National Spherical Torus Experiment, NSTX [M. Ono et al., Nucl.
      Fusion 40, 557 (2000)]. The diagnostic, based on active charge-exchange
      recombination spectroscopy, can measure at up to six radial locations with
      maximum sampling rate of 5 kHz. The system is interfaced in real time with the
      NSTX plasma control system, in order to feed back on plasma velocity by means of
      actuators such as neutral beams and external coils. The paper describes the
      design criteria and implementation of the diagnostic. Examples from the initial
      tests of the system during neon glows are also discussed.

PMID- 22462919
TI  - Impact of plasma noise on a direct thrust measurement system.
AB  - In order to evaluate the accuracy and sensitivity of a pendulum-type thrust
      measurement system, a linear variable differential transformer (LVDT) and a laser
      optical displacement sensor have been used simultaneously to determine the
      displacement resulting from an applied thrust. The LVDT sensor uses an analog
      interface, whereas the laser sensor uses a digital interface to communicate the
      displacement readings to the data acquisition equipment. The data collected by
      both sensors show good agreement for static mass calibrations and validation with
      a cold gas thruster. However, the data obtained using the LVDT deviate
      significantly from that of the laser sensor when operating two varieties of
      plasma thrusters: a radio frequency (RF) driven plasma thruster, and a DC powered
      plasma thruster. Results establish that even with appropriate shielding and
      signal filtering the LVDT sensor is subject to plasma noise and radio frequency
      interactions which result in anomalous thrust readings. Experimental data show
      that the thrust determined using the LVDT system in a direct current plasma
      environment and a RF discharge is approximately a factor of three higher than the
      thrust values obtained using a laser sensor system for the operating conditions
      investigated. These findings are of significance to the electric propulsion
      community as LVDT sensors are often utilized in thrust measurement systems and
      accurate thrust measurement and the reproducibility of thrust data is key to
      analyzing thruster performance. Methods are proposed to evaluate system
      susceptibility to plasma noise and an effective filtering scheme presented for DC
      discharges.

PMID- 22462920
TI  - Simultaneous measurements of the parallel and perpendicular ion temperature with
      a pinhole probe in the scrape-off-layer of the tokamak ISTTOK.
AB  - A pinhole probe (PHP) for the simultaneous measurement of the parallel,
      T(parallel), and perpendicular, T(perpendicular), ion temperature has been
      designed and tested in the scrape-off-layer (SOL) plasma of the tokamak ISTTOK.
      The PHP consists of a tunnel immersed into the plasma parallel to magnetic field
      and an ion collector. One end of the tunnel is covered with a thin foil that has
      a pinhole sampling ions from the plasma. The other end of the tunnel (close to
      the negatively biased collector) is covered with a fine-mesh screen. The
      possibility of performing an analytical description of the PHP current-to-voltage
      characteristics obtained on the collector when biasing the tunnel simplifies the
      interpretation of the results. The PHP operation has been previously tested in
      T(parallel), T(perpendicular) measurements in low temperature weekly magnetized
      plasma [H. Mase, T. Honzava, and G. Miyamoto, J. Appl. Phys. 49(10), 5171
      (1978)]. In this paper, the PHP operation in the SOL of the tokamak ISTTOK is
      described, and the first results of T(parallel) and T(perpendicular) measurements
      are presented. The obtained results demonstrate strong (~30%) variation of
      T(parallel) and T(perpendicular) on a time scale of 0.5 ms, and general
      predominance of T(parallel) > T(perpendicular) anisotropy (T(parallel
      mean)/T(perpendicular mean) ~ 1.5) during plasma shot.

PMID- 22462921
TI  - Multi-chord fiber-coupled interferometer with a long coherence length laser.
AB  - This paper describes a 561 nm laser heterodyne interferometer that provides time
      resolved measurements of line-integrated plasma electron density within the range
      of 10(15)-10(18) cm(-2). Such plasmas are produced by railguns on the plasma
      liner experiment, which aims to produce MUs-, cm-, and Mbar-scale plasmas through
      the merging of 30 plasma jets in a spherically convergent geometry. A long
      coherence length, 320 mW laser allows for a strong, sub-fringe phase-shift signal
      without the need for closely matched probe and reference path lengths. Thus, only
      one reference path is required for all eight probe paths, and an individual probe
      chord can be altered without altering the reference or other probe path lengths.
      Fiber-optic decoupling of the probe chord optics on the vacuum chamber from the
      rest of the system allows the probe paths to be easily altered to focus on
      different spatial regions of the plasma. We demonstrate that sub-fringe
      resolution capability allows the interferometer to operate down to line
      integrated densities of the order of 5 * 10(15) cm(-2).

PMID- 22462922
TI  - Development and characterization of very dense submillimetric gas jets for laser
      plasma interaction.
AB  - We report on the characterization of recently developed submillimetric He gas
      jets with peak density higher than 10(21) atoms/cm(3) from cylindrical and
      slightly conical nozzles of throat diameter of less than 400 MUm. Helium gas at
      pressure 300-400 bar has been developed for this purpose to compensate the nozzle
      throat diameter reduction that affects the output mass flow rate. The fast
      switching electro-valve enables to operate the jet safely for multi-stage vacuum
      pump assembly. Such gaseous thin targets are particularly suitable for laser
      plasma interaction studies in the unexplored near-critical regime.

PMID- 22462923
TI  - Miniature active damping stage for scanning probe applications in ultra high
      vacuum.
AB  - Scanning probe microscope (SPM) experiments demand a low vibration level to
      minimize the external influence on the measured signal. We present a miniature
      six-degree of freedom active damping stage based on a Gough-Stewart platform
      (hexapod) which is positioned in ultra high vacuum as close to the SPM as
      possible. In this way, vibrations originating from the experimental setup can be
      effectively reduced providing a quiet environment for the SPM. In addition, the
      hexapod provides a rigid reference point, which facilitates wiring as well as
      sample transfer. We outline the main working principle and show that for scanning
      tunneling microscopy (STM) measurements of a Si(111) 7 * 7 surface, the hexapod
      significantly improves the stability and quality of the topographic images.

PMID- 22462924
TI  - Determining the equation of state of amorphous solids at high pressure using
      optical microscopy.
AB  - A method to determine the volumetric equation of state of amorphous solids using
      optical microscopy in a diamond anvil cell is described. The method relies on two
      dimensional image acquisition and analysis to quantify changes in the projected
      image area with compression. The area analysis methods prove to be robust against
      improper focusing and lighting conditions while providing the accuracy necessary
      to deduce small area changes, which correspond to small volume changes in an
      isotropic material. The image capture, area analysis method is used to determine
      the compression of cubic crystals, yielding results in good agreement with
      diffraction and volumetric measurements. As a proof of concept, the equation of
      state of amorphous red phosphorus is measured up to 12 GPa under hydrostatic
      conditions where the quantified volume change between the red and black phases is
      approximately DeltaV/V(0) ~ 0.05 after a reduction of volume nearing 35% at 8
      GPa. A large hysteresis is present during decompression and eventually results in
      a 15% permanent densification relative to the starting volume, which is
      attributed to a pressure induced crystallization from red to black phosphorus.
      The robustness of the technique is also demonstrated by measuring the equation of
      state of GeSe(2) glasses for semi transparent samples and As(2)O(3) in which gold
      coating is used as a contrasting aid.

PMID- 22462925
TI  - An in-vacuum x-ray diffraction microscope for use in the 0.7-2.9 keV range.
AB  - A dedicated in-vacuum coherent x-ray diffraction microscope was installed at the
      2-ID-B beamline of the Advanced Photon Source for use with 0.7-2.9 keV x-rays.
      The instrument can accommodate three common implementations of diffractive
      imaging; plane wave illumination; defocused-probe (Fresnel diffractive imaging)
      and scanning (ptychography) using either a pinhole, focused or defocused probe.
      The microscope design includes active feedback to limit motion of the optics with
      respect to the sample. Upper bounds on the relative optics-to-sample displacement
      have been measured to be 5.8 nm(v) and 4.4 nm(h) rms/h using capacitance
      micrometry and 27 nm/h using x-ray point projection imaging. The stability of the
      measurement platform and in-vacuum operation allows for long exposure times, high
      signal-to-noise and large dynamic range two-dimensional intensity measurements to
      be acquired. Finally, we illustrate the microscope's stability with a recent
      experimental result.

PMID- 22462926
TI  - Background-free imaging of plasmonic structures with cross-polarized apertureless
      scanning near-field optical microscopy.
AB  - We present advances in experimental techniques of apertureless scanning near
      field optical microscopy (aSNOM). The rational alignment procedure we outline is
      based upon a phase singularity that occurs while scanning polarizers around the
      nominal cross-polarized configuration of s-polarized excitation and p-polarized
      detection. We discuss the theoretical origin of this topological feature of the
      setup, which is robust against small deviations, such as minor tip misalignment
      or shape variations. Setting the polarizers to this singular configuration point
      eliminates all background signal, allowing for reproducible plasmonic eigenmode
      mapping with optimal signal-to-noise ratio.

PMID- 22462927
TI  - Superficial magnetic imaging by an xy-scanner of three magnetoresistive channels.
AB  - A scanning system developed for planar magnetic surfaces composed of a moving
      line of three magnetoresistive ultrasensitive transducers, complemented by a
      signal conditioning circuit is presented. After the calibration of the sensors,
      it was used to determine magnetized surface images with different shapes to
      evaluate the sensitivity of the device, and the images are represented in gray
      levels on a scale from 0 to 255 intensities, to get a visual representation of
      the magnetic field strength. The device is shown to be sensitive enough to detect
      gradients homogeneities and discontinuities in the magnetic field maps and images
      of magnetic susceptibility.

PMID- 22462928
TI  - Methods and instrumentation for piezoelectric motors.
AB  - Because of their compact form factor and rigidity, piezoelectric motors are used
      in scanning probe microscopes that operate at low temperature and high magnetic
      field. Here we present detailed information to facilitate the assembly,
      operation, and characterization of inertial motors. Specifically, a model of the
      motor is developed and used to identify different regions of operation. Drive
      electronics with high slew rate and large output current are described and a step
      by-step procedure for assembling piezoelectric shear stacks is detailed.
      Additionally, a novel reflective object sensor is described and used to
      characterize a Pan-style inertial motor that was designed and assembled using the
      concepts presented in this paper.

PMID- 22462929
TI  - Ultra compact multitip scanning tunneling microscope with a diameter of 50 mm.
AB  - We present a multitip scanning tunneling microscope (STM) where four independent
      STM units are integrated on a diameter of 50 mm. The coarse positioning of the
      tips is done under the control of an optical microscope or scanning electron
      microscopy in vacuum. The heart of this STM is a new type of piezoelectric coarse
      approach called KoalaDrive. The compactness of the KoalaDrive allows building a
      four-tip STM as small as a single-tip STM with a drift of less than 0.2  nm/min
      at room temperature and lowest resonance frequencies of 2.5  kHz (xy) and 5.5 
      kHz (z). We present as examples of the performance of the multitip STM four point
      measurements of silicide nanowires and graphene.

PMID- 22462930
TI  - An x-space magnetic particle imaging scanner.
AB  - Magnetic particle imaging (MPI) is an imaging modality with great promise for
      high-contrast, high-sensitivity imaging of iron oxide tracers in animals and
      humans. In this paper, we present the first x-space MPI hardware and
      reconstruction software; show experimentally measured signals; detail our
      reconstruction technique; and present images of resolution and "angiography"
      phantoms.

PMID- 22462931
TI  - Dual frequency open-loop electric potential microscopy for local potential
      measurements in electrolyte solution with high ionic strength.
AB  - Recent development of open-loop electric potential microscopy (OL-EPM) has
      enabled to measure local potential distribution at a solid/liquid interface.
      However, the operating environment of OL-EPM has been limited to a weak
      electrolyte solution (<1 mM). This has significantly limited its application
      range in biology and chemistry. To overcome this limitation, we have developed
      dual frequency (DF) mode OL-EPM. In the method, an ac bias voltage consisting of
      two frequency components at f(1) and f(2) is applied between a tip and sample.
      The local potential is calculated from the amplitudes of the f(1) and |f(1) -
      f(2)| components of the electrostatic force. In contrast to the conventional
      single frequency (SF) mode OL-EPM, the detection of the 2f(1) component is not
      required in DF mode. Thus, the maximum bias modulation frequency in DF mode is
      twice as high as that in SF mode. The high bias modulation frequency used in DF
      mode prevents the generation of electrochemical reactions and redistribution of
      ions and water, which enables to operate OL-EPM even in a strong electrolyte
      solution. In this study, we have performed potential measurements of
      nanoparticles on a graphite surface in 1 and 10 mM NaCl solution. The results
      demonstrate that DF mode OL-EPM allows measurements of local potential
      distribution in 10 mM electrolyte solution.

PMID- 22462932
TI  - A calorimetric method to detect a weak or distributed latent heat contribution at
      first order magnetic transitions.
AB  - Microcalorimetry has proven to be a versatile tool to investigate first order
      magnetic phase transitions as it can be used in different experimental modes to
      separate the latent heat from heat capacity. However, the methodology fails if
      the latent heat contribution is below instrumental resolution of 10 nJ. If the
      nucleation size of the new phase is much less than 100 MUm, the typical size of
      the fragment measured, the latent heat could appear to be too distributed in
      temperature or magnetic field to be detected. Here, we show that for certain
      classes of magnetic transition, our microcalorimetry technique can be extended to
      enable an estimate of the latent heat to be obtained from a combination of heat
      capacity and magnetic measurements. This technique is best suited for material
      systems with weakly first order phase transitions, or highly distributed due to
      inhomogeneity.

PMID- 22462933
TI  - Differential alternating current chip calorimeter for in situ investigation of
      vapor-deposited thin films.
AB  - Physical vapor deposition can be used to produce thin films with interesting
      material properties including extraordinarily stable organic glasses. We describe
      an ac chip calorimeter for in situ heat capacity measurements of as-deposited
      nanometer thin films of organic glass formers. The calorimetric system is based
      on a differential ac chip calorimeter which is placed in the vacuum chamber for
      physical vapor deposition. The sample is directly deposited onto one calorimetric
      chip sensor while the other sensor is protected against deposition. The device
      and the temperature calibration procedure are described. The latter makes use of
      the phase transitions of cyclopentane and the frequency dependence of the dynamic
      glass transition of toluene and ethylbenzene. Sample thickness determination is
      based on a finite element modeling of the sensor sample arrangement. In the
      modeling, a layer of toluene was added to the sample sensor and its thickness was
      varied in an iterative way until the model fit the experimental data.

PMID- 22462934
TI  - Two-channel impedance spectroscopy for the simultaneous measurement of two
      samples.
AB  - We describe a dielectric relaxation technique, which allows one to obtain a very
      accurate comparison of the behavior of two different samples. The key feature is
      the simultaneous impedance measurement on two capacitors that can share a common
      center electrode, implying that the same voltage is applied to both samples and
      that only a single gain/phase analyzer is required. The capabilities of this
      technique have been examined by comparing the dynamics of protonated and
      deuterated 1-propanol samples using this dual-channel analyzer in the frequency
      range of 10(-2)-10(6) Hz and in the temperature range of 110-160 K, after
      calibrating the system using the same sample in both, channel 1 and channel 2.
      For many supercooled liquids, the high sensitivity of the dielectric relaxation
      behavior on temperature prevents a meaningful comparison of nearly identical
      dynamics on the basis of two separate measurements. Based on this dual-channel
      method, we observe that a deuterated 1-propanol sample displays small but
      systematic deviations from the relaxation spectra of its protonated counterpart,
      which would not be observable in separate dielectric measurements. Many other
      applications can be envisioned where simultaneous or differential impedance
      measurements are advantageous.

PMID- 22462935
TI  - Modified electrical transport probe design for standard magnetometer.
AB  - Making electrical transport measurements on a material is often a time consuming
      process that involves testing a large number of samples. It is thus inconvenient
      to wire up and rewire samples onto a sample probe. We therefore present a method
      of modifying Quantum Design's MPMS SQUID magnetometer transport probe that
      simplifies the process of sample mounting. One of the difficulties to overcome is
      the small diameter of the sample space. A small socket is designed and mounted on
      the probe so that various samples mounted on individual headers can be readily
      exchanged in the socket. We also present some test results on the topological
      insulator Bi(2)Te(2)Se using the modified probe.

PMID- 22462936
TI  - Simultaneous structure and elastic wave velocity measurement of SiO2 glass at
      high pressures and high temperatures in a Paris-Edinburgh cell.
AB  - An integration of multi-angle energy-dispersive x-ray diffraction and ultrasonic
      elastic wave velocity measurements in a Paris-Edinburgh cell enabled us to
      simultaneously investigate the structures and elastic wave velocities of
      amorphous materials at high pressure and high temperature conditions. We report
      the first simultaneous structure and elastic wave velocity measurement for SiO(2)
      glass at pressures up to 6.8 GPa at around 500 degrees C. The first sharp
      diffraction peak (FSDP) in the structure factor S(Q) evidently shifted to higher
      Q with increasing pressure, reflecting the shrinking of intermediate-range order,
      while the Si-O bond distance was almost unchanged up to 6.8 GPa. In correlation
      with the shift of FSDP position, compressional wave velocity (Vp) and Poisson's
      ratio increased markedly with increasing pressure. In contrast, shear wave
      velocity (Vs) changed only at pressures below 4 GPa, and then remained unchanged
      at ~4.0-6.8 GPa. These observations indicate a strong correlation between the
      intermediate range order variations and Vp or Poisson's ratio, but a complicated
      behavior for Vs. The result demonstrates a new capability of simultaneous
      measurement of structures and elastic wave velocities at high pressure and high
      temperature conditions to provide direct link between microscopic structure and
      macroscopic elastic properties of amorphous materials.

PMID- 22462937
TI  - Design of a vector magnet for the measurements of anisotropic magnetoresistance
      and rotational magneto-optic Kerr effect.
AB  - A vector magnet is designed and assembled with two electromagnets to produce a
      rotational magnetic field in any direction within a plane. This design allows a
      rotation of the magnetic field without a mechanical rotation of the magnets. The
      fast speed of the field rotation (~10 s for a complete 360 degrees  rotation) and
      the stability against mechanical vibration easily overcome the slow drifting
      effect in anisotropic magnetoresistance (AMR) and rotational magneto-optic Kerr
      effect (ROTMOKE) measurements. As an example we applied this vector magnet to
      carry out AMR and ROTMOKE measurements on epitaxial growth of Fe(10 nm)/MgO(001)
      films. The result demonstrates the stability and high quality of the vector
      magnet in determining the magnetic anisotropy of magnetic thin films using AMR
      and ROTMOKE techniques.

PMID- 22462938
TI  - A cryogen-free dilution refrigerator based Josephson qubit measurement system.
AB  - We develop a small-signal measurement system on cryogen-free dilution
      refrigerator which is suitable for superconducting qubit studies. Cryogen-free
      refrigerators have several advantages such as less manpower for system operation
      and large sample space for experiment, but concern remains about whether the
      noise introduced by the coldhead can be made sufficiently low. In this work, we
      demonstrate some effective approaches of acoustic isolation to reduce the noise
      impact. The electronic circuit that includes the current, voltage, and microwave
      lines for qubit coherent state measurement is described. For the current and
      voltage lines designed to have a low pass of dc-100 kHz, we show that the
      measurements of Josephson junction's switching current distribution with a width
      down to 1 nA, and quantum coherent Rabi oscillation and Ramsey interference of
      the superconducting qubit can be successfully performed.

PMID- 22462939
TI  - Online and offline experimental techniques for polycyclic aromatic hydrocarbons
      recovery and measurement.
AB  - The implementation of techniques aimed at improving engine performance and
      reducing particulate matter (PM) pollutant emissions is strongly influenced by
      the limited understanding of the polycyclic aromatic hydrocarbons (PAH) formation
      chemistry, in combustion devices, that produces the PM emissions. New
      experimental results which examine the formation of multi-ring compounds are
      required. The present investigation focuses on two techniques for such an
      experimental examination by recovery of PAH compounds from a typical combustion
      oriented experimental apparatus. The online technique discussed constitutes an
      optimal solution but not always feasible approach. Nevertheless, a detailed
      description of a new online sampling system is provided which can serve as
      reference for future applications to different experimental set-ups. In
      comparison, an offline technique, which is sometimes more experimentally feasible
      but not necessarily optimal, has been studied in detail for the recovery of a
      variety of compounds with different properties, including naphthalene, biphenyl,
      and iodobenzene. The recovery results from both techniques were excellent with an
      error in the total carbon balance of around 10% for the online technique and an
      uncertainty in the measurement of the single species of around 7% for the offline
      technique. Although both techniques proved to be suitable for measurement of
      large PAH compounds, the online technique represents the optimal solution in view
      of the simplicity of the corresponding experimental procedure. On the other hand,
      the offline technique represents a valuable solution in those cases where the
      online technique cannot be implemented.

PMID- 22462940
TI  - Gate effects on DNA translocation through silicon dioxide nanopore.
AB  - The effects of gate voltage on the translocation of DNA molecules through a
      nanopore are studied. A twenty-fold increase in the translocation time is
      observed with a positive gate voltage applied, without changing too much of the
      ionic current. The amplitude of the current blockage by the DNA molecules was
      reduced by roughly the same factor. At the same time, the number of the blocking
      events decreases significantly. The applied gate voltage also modulates the
      scatter plot of the amplitude of the current blockage against the dwell time. The
      observations are consistent with the recent theoretical results.

PMID- 22462941
TI  - A new laser Doppler flowmeter prototype for depth dependent monitoring of skin
      microcirculation.
AB  - Laser Doppler flowmetry (LDF) is now commonly used in clinical research to
      monitor microvascular blood flow. However, the dependence of the LDF signal on
      the microvascular architecture is still unknown. That is why we propose a new
      laser Doppler flowmeter for depth dependent monitoring of skin microvascular
      perfusion. This new laser Doppler flowmeter combines for the first time, in a
      device, several wavelengths and different spaced detection optical fibres. The
      calibration of the new apparatus is herein presented together with in vivo
      validation. Two in vivo validation tests are performed. In the first test,
      signals collected in the ventral side of the forearm are analyzed; in the second
      test, signals collected in the ventral side of the forearm are compared with
      signals collected in the hand palm. There are good indicators that show that
      different wavelengths and fibre distances probe different skin perfusion layers.
      However, multiple scattering may affect the results, namely the ones obtained
      with the larger fibre distance. To clearly understand the wavelength effect in
      LDF measurements, other tests have to be performed.

PMID- 22462942
TI  - Accurate and low jitter time-interval generators based on phase shifting method.
AB  - The paper describes two time-interval generators based on the phase shifting
      method. The first one utilizes the digital clock manager units integrated in a
      field programmable gate array (FPGA) device and has jitter below 65 ps (rms) over
      the range of 4 ns-50 ms, while the second one utilizes a separate direct digital
      synthesizer and has jitter below 15 ps (rms) over the range of 10.2 ns-50 ms. The
      phase shifting method can be used to design new low-cost and high-precision time
      interval generators using the popular FPGA technology.

PMID- 22462943
TI  - Design and testing of multi-standard waveguide couplers.
AB  - Most applications that use waveguides are designed for a single frequency or
      single band of frequency, and thus the waveguide dimensions are chosen for single
      mode operation. In special cases where multiple frequencies across multiple bands
      are needed (i.e., probing the temporal response of decaying plasma using a cw
      source that is generated by a pulsed source), special techniques must be used in
      order to implement both sources into a single waveguide structure. This paper
      presents two types of couplers designed to implement x-band frequencies into an s
      band system with a large coupling coefficient (< -10 dB) and small reflection
      coefficient (> -10 dB) at the design frequency of 11 GHz. Along with a discussion
      on the design procedure, a detailed description on the parameter optimization and
      initial values estimation is presented. The custom waveguide structures were
      tested utilizing an Agilent E8364B PNA network analyzer, and showed reasonable
      agreement with the simulated performance over the frequency range of interest.

PMID- 22462944
TI  - Development of a compact cylindrical reaction cavity for a microwave dielectric
      heating system.
AB  - This paper describes a compact reaction cavity for a microwave-assisted synthesis
      system. The microwave dielectric heating is a key technology to improve
      synthesizing yield, however, the large size of the microwave generation and
      reaction parts in an all-in-one system is a major obstacle when applying the
      technique to various systems, of which the installation space is limited. For
      this particular problem, a compact stand-alone cylindrical reaction cavity was
      developed in the current study. A microwave excited from a monopole probe, which
      is inserted into the side of the cavity, is transferred to a reaction mixture
      through the upper hole of the cavity. The cavity is miniaturized by filling it
      with an alumina ceramic dielectric. Fine-tuning of the resonance frequency
      becomes available by controlling the length of the inserted screw between the
      probe and the upper hole. The physical properties of the cavity were simulated
      using high frequency structural simulator (HFSS) and the produced cavity was
      tested using an Agilent E8357A network analyzer. The test results show that the
      developed cavity is able to send enough energy to various solvents.

PMID- 22462945
TI  - Low temperature laser scanning microscopy of a superconducting radio-frequency
      cavity.
AB  - An apparatus was developed to obtain, for the first time, 2D maps of the surface
      resistance of the inner surface of an operating superconducting radio-frequency
      niobium cavity by a low-temperature laser scanning microscopy technique. This
      allows identifying non-uniformities of the surface resistance with a spatial
      resolution of about 2.4 mm and surface resistance resolution of ~1 MUOmega at 3.3
      GHz. A signal-to-noise ratio of about 10 dB was obtained with 240 mW laser power
      and 1 Hz modulation frequency. The various components of the apparatus, the
      experimental procedure and results are discussed in detail in this contribution.

PMID- 22462946
TI  - Investigation and compensation of the nonlinear response in photomultiplier tubes
      for quantitative single-shot measurements.
AB  - A concept for time-sensitive optical detectors is described that shows how to
      confirm whether the detection device is operating in the linear response regime.
      By evaluating the recorded time decay of a thermographic phosphor, even weak
      saturation effects far from obvious situations can be identified and further
      related to either optical or electrical saturation. The concept has been
      validated by running a PMT detector close to saturation and exposing it to the
      optical signal decay of two different thermographic phosphors, La(2)O(2)S:Eu and
      CdWO(4). It was confirmed that short but intense light exposures at the beginning
      of an individual time decay influence the detector response for the rest of the
      decaying signal including temporal areas, where the anode current has dropped
      well below the manufacturer specified current limit. Such situations are common
      when applying, e.g., phosphor thermometry where it is necessary to retrieve the
      full decay curve from a single-shot event, i.e., standard techniques based on
      single-photon counting are omitted. Finally, means of compensation are introduced
      in order to facilitate the retrieval of useful information from the measurement
      data when operation in the non-linear response regime is inevitable.

PMID- 22462947
TI  - Thermal contact conductance of demountable in vacuum copper-copper joint between
      14 and 100 K.
AB  - Thermal contact conductance (TCC) at material interfaces has a great impact upon
      the efficiency of cooling in cryogenic instruments, and is thus a crucial design
      parameter. Lack of reliable numerical data for demountable in vacuum bare
      (uncoated, dry, and without interposers) copper-copper joints prompted us to
      carry out systematic studies of TCC over the temperature range 14-100 K. We
      measured TCC as function of applied force for the contacts with surface roughness
      R(a) = 0.2, 1.6, and 3.2 MUm. It is seen that with increasing temperature, the
      TCC of bare Cu-Cu contact initially rises following a generic power law
      dependency T(gamma) with gamma = 1.25 +/- 0.02, reaching a maximum value at 40-50
      K. TCC then decreases as temperature continues to rise towards 100 K. We show
      results that match those in the literature from low (4-20 K) and high (100-300 K)
      temperature domains, resulting in a unified smooth curve of temperature
      dependency of TCC for bare Cu-Cu joints. Temperature dependence is then described
      in a phenomenological model, accounting for the effects of changes in bulk
      conductivity and surface hardness with temperature. This model consistently
      explains the observed power law dependence of TCC as function of applied force
      and changes caused by roughness of contact surfaces.

PMID- 22462948
TI  - Simultaneous observation of acoustic resonance phenomena at both surfaces of a
      plate coated with thin layers.
AB  - Acoustic resonance phenomena at the front and back surfaces of a plate coated
      with thin layers were successfully observed in the amplitude spectrum of the back
      surface echo. The amplitude ratio of spectra with and without layers takes its
      maximum and minimum values at the resonant frequencies of the front and back
      coatings and both frequencies can clearly be distinguished from each other. As an
      application, the thicknesses of the front and back coatings on a steel plate were
      measured simultaneously using their resonant frequencies, thus verifying the
      validity of the principle.

PMID- 22462949
TI  - Time-resolved monitoring of cavitation activity in megasonic cleaning systems.
AB  - The occurrence of acoustic cavitation in the cleaning liquid is a crucial
      precondition for the performance of megasonic cleaning systems. Hence, a
      fundamental understanding of the impact of different parameters of the megasonic
      process on cavitation activity is necessary. A setup capable of synchronously
      measuring sonoluminescence and acoustic emission originating from acoustically
      active bubbles is presented. The system also includes a high-speed-stroboscopic
      Schlieren imaging system to directly visualize the influence of cavitation
      activity on the Schlieren contrast and resolvable bubbles. This allows a thorough
      characterization of the mutual interaction of cavitation bubbles with the sound
      field and with each other. Results obtained during continuous sonication of argon
      saturated water at various nominal power densities indicate that acoustic
      cavitation occurs in a cyclic manner, during which periods of stable and inertial
      cavitation activity alternate. The occurrence of higher and ultraharmonics in the
      acoustic emission spectra is characteristic for the stable cavitation state. The
      inertial cavitation state is characterized by a strong attenuation of the sound
      field, the explosive growth of bubbles and the occurrence of broadband components
      in the acoustic spectra. Both states can only be sustained at sufficiently high
      intensities of the sound field. At lower intensities, their occurrences are
      limited to short, random bursts. Cleaning activity can be linked to the
      cavitation activity through the measurement of particle removal on standard 200
      mm silicon wafers. It is found that the particle removal efficiency is reduced,
      when a continuous state of cavitation activity ceases to exist.

PMID- 22462950
TI  - Simple and compact capacitive voltage probe for measuring voltage impulses up to
      0.5 MV.
AB  - The paper describes a simple and compact 0.5 MV high-voltage capacitive probe
      developed in common by Universite de Pau (France) and Loughborough University
      (UK). Design details are provided, together with a simple and straightforward
      methodology developed to assess the characteristics of high-voltage probes. The
      technique uses a 4 kV pulsed arrangement combined with results from a 2D electric
      field solver and a thorough PSpice circuit analysis. Finally, a practical example
      of high-voltage measurement performed using such a probe during the development
      phase of a high power microwave generator is provided.

PMID- 22462951
TI  - A novel method of temperature compensation for piezoresistive microcantilever
      based sensors.
AB  - Microcantilever with integrated piezoresistor has been applied to in situ surface
      stress measurement in the field of biochemical sensors. It is well known that
      piezoresistive cantilever-based sensors are sensitive to ambient temperature
      changing due to highly temperature-dependent piezoresistive effect and mismatch
      in thermal expansion of composite materials. This paper proposes a novel method
      of temperature drift compensation for microcantilever-based sensors with a
      piezoresistive full Wheatstone bridge integrated at the clamped ends by
      subtracting the amplified output voltage of the reference cantilever from the
      output voltage of the sensing cantilever through a simple temperature
      compensating circuit. Experiments show that the temperature drift of
      microcantilever sensors can be significantly reduced by the method.

PMID- 22462952
TI  - Development of flexure based 6-degrees of freedom parallel nano-positioning
      system with large displacement.
AB  - This paper details the development of a novel flexure jointed precision parallel
      nano-positioning system in combination with piezo-electric stepping motor for the
      application of precise optics alignment. The characteristics of the developed
      system are evaluated in this paper by the simulation and experiments. Based on
      the precision piezo-electric stepping motor and flexure joints, a high precision
      motion is obtained. Results of this paper include that of a translation
      resolution of 15 nm and a rotational resolution of 0.14 arc sec being achieved.
      In addition, the piezo-electric stepping motors provide a power-off hold
      characteristic to the system. Meanwhile, the parallel structure provides the high
      dynamic bandwidth of the lowest resonant frequency of 396.1 Hz. The symmetric
      structure is advantageous for thermal variation. To increase the motion range of
      the system, all of flexure joints are designed specially and the coupled
      workspace of +/-2 mm * +/-2 mm * +/-2 mm * +/-2 degrees  * +/-2 degrees  * +/-2
      degrees  is achieved. The overall size of the designed system is Phi350 mm * 120
      mm.

PMID- 22462953
TI  - Fresnel-reflection-based fiber sensor for high-temperature measurement.
AB  - A fiber sensor system was developed to measure high temperatures. The system
      consists of a diode laser as the light source, three optical couplers, two
      sensing fiber ends, and two photodetectors. The measurement is based on the
      relative Fresnel reflection intensity and the thermo-optic effect of the fiber.
      The application of this relative technique can operatively eliminate the errors
      resulting from light source fluctuations and the effect of the environment. The
      stability of the system for long-duration measurements can also be effectively
      improved.

PMID- 22462954
TI  - A single-solenoid pulsed-magnet system for single-crystal scattering studies.
AB  - We present a pulsed-magnet system that enables x-ray single-crystal diffraction
      in addition to powder and spectroscopic studies with the magnetic field applied
      on or close to the scattering plane. The apparatus consists of a single large
      bore solenoid, cooled by liquid nitrogen. A second independent closed-cycle
      cryostat is used for cooling samples near liquid helium temperatures. Pulsed
      magnetic fields close to ~30 T with a zero-to-peak-field rise time of ~2.9 ms are
      generated by discharging a 40 kJ capacitor bank into the magnet coil. The unique
      characteristic of this instrument is the preservation of maximum scattering angle
      (~23.6 degrees ) on the entrance and exit sides of the magnet bore by virtue of a
      novel double-funnel insert. This instrument will facilitate x-ray diffraction and
      spectroscopic studies that are impractical, if not impossible, to perform using
      split-pair and narrow-opening solenoid magnets. Furthermore, it offers a
      practical solution for preserving optical access in future higher-field pulsed
      magnets.

PMID- 22462955
TI  - CO2 laser pulse shortening by laser ablation of a metal target.
AB  - A repeatable and flexible technique for pulse shortening of laser pulses has been
      applied to transversely excited atmospheric (TEA) CO(2) laser pulses. The
      technique involves focusing the laser output onto a highly reflective metal
      target so that plasma is formed, which then operates as a shutter due to strong
      laser absorption and scattering. Precise control of the focused laser intensity
      allows for timing of the shutter so that different temporal portions of the pulse
      can be reflected from the target surface before plasma formation occurs. This
      type of shutter enables one to reduce the pulse duration down to ~2 ns and to
      remove the low power, long duration tails that are present in TEA CO(2) pulses.
      The transmitted energy is reduced as the pulse duration is decreased but the
      reflected power is ~10 MW for all pulse durations. A simple laser heating model
      verifies that the pulse shortening depends directly on the plasma formation time,
      which in turn is dependent on the applied laser intensity. It is envisaged that
      this plasma shutter will be used as a tool for pulse shaping in the search for
      laser pulse conditions to optimize conversion efficiency from laser energy to
      useable extreme ultraviolet (EUV) radiation for EUV source development.

PMID- 22462956
TI  - Combined ellipsometry and refractometry technique for characterisation of liquid
      crystal based nanocomposites.
AB  - Spectroscopic ellipsometry is a technique especially well suited to measure the
      effective optical properties of a composite material. However, as the sample is
      optically thick and anisotropic, this technique loses its accuracy for two
      reasons: anisotropy means that two parameters have to be determined (ordinary and
      extraordinary indices) and optically thick means a large order of interference.
      In that case, several dielectric functions can emerge out of the fitting
      procedure with a similar mean square error and no criterion to discriminate the
      right solution. In this paper, we develop a methodology to overcome that
      drawback. It combines ellipsometry with refractometry. The same sample is used in
      a total internal reflection (TIR) setup and in a spectroscopic ellipsometer. The
      number of parameters to be determined by the fitting procedure is reduced in
      analysing two spectra, the correct final solution is found by using the TIR
      results both as initial values for the parameters and as check for the final
      dielectric function. A prefitting routine is developed to enter the right initial
      values in the fitting procedure and so to approach the right solution. As an
      example, this methodology is used to analyse the optical properties of BaTiO(3)
      nanoparticles embedded in a nematic liquid crystal. Such a methodology can also
      be used to analyse experimentally the validity of the mixing laws, since
      ellipsometry gives the effective dielectric function and thus, can be compared to
      the dielectric function of the components of the mixture, as it is shown on the
      example of BaTiO(3)/nematic composite.

PMID- 22462957
TI  - A cryogenic circulating advective multi-pass absorption cell.
AB  - A novel absorption cell has been developed to enable a spectroscopic survey of a
      broad range of polycyclic aromatic hydrocarbons (PAH) under astrophysically
      relevant conditions and utilizing a synchrotron radiation continuum to test the
      still controversial hypothesis that these molecules or their ions could be
      carriers of the diffuse interstellar bands. The cryogenic circulating advective
      multi-pass absorption cell resembles a wind tunnel; molecules evaporated from a
      crucible or injected using a custom gas feedthrough are entrained in a laminar
      flow of cryogenically cooled buffer gas and advected into the path of the
      synchrotron beam. This system includes a multi-pass optical White cell enabling
      absorption path lengths of hundreds of meters and a detection sensitivity to
      molecular densities on the order of 10(7) cm(-3). A capacitively coupled radio
      frequency dielectric barrier discharge provides ionized and metastable buffer gas
      atoms for ionizing the candidate molecules via charge exchange and the Penning
      effect. Stronger than expected clustering of PAH molecules has slowed efforts to
      record gas phase PAH spectra at cryogenic temperatures, though such clusters may
      play a role in other interstellar phenomena.

PMID- 22462958
TI  - Single lens photometric machine vision with 3D imaging for fiber-to-chip
      coupling.
AB  - A single lens photometric machine vision (SLPMV) optical microbench is presented
      and built for fiber-to-chip coupling. By a rotation mechanics in SLPMV, the multi
      view-camera can scan the various surface status of the chips coupled. To realize
      3D imaging more explicitly, the modified photometric stereo algorithm is proposed
      through acquiring the images of weak saturation, matching the scanning
      illuminative angles, and rectifying rectangularly the original images. The
      reconstructed images have had similar qualities as those obtained by scanning
      electron microscopy and have unveiled the detailed information obscured in the 2D
      images. For the InP-based optical waveguide chip coupled with wedge-shaped fiber,
      the insertion loss tested on the SLPMV is 3 dB less than one on the conventional
      testing station. The SLPMV could serve as a more cost-effective and compact
      scientific observation instrumentation in imaging informatics than commercial
      ones.

PMID- 22462959
TI  - Highly precise and compact ultrahigh vacuum rotary feedthrough.
AB  - The precision and rigidity of compact ultrahigh vacuum (UHV) rotary feedthroughs
      were substantially improved by preparing and installing an optimal crossed roller
      bearing with mounting holes. Since there are mounting holes on both the outer and
      inner races, the bearing can be mounted directly to rotary and stationary stages
      without any fixing plates and housing. As a result, it is possible to increase
      the thickness of the bearing or the size of the rolling elements in the bearing
      without increasing the distance between the rotating and fixing International
      Conflat flanges of the UHV rotary feedthrough. Larger rolling elements enhance
      the rigidity of the UHV rotary feedthrough. Moreover, owing to the structure
      having integrated inner and outer races and mounting holes, the performance is
      almost entirely unaffected by the installation of the bearing, allowing for a
      precise optical encoder to be installed in the compact UHV rotary feedthrough.
      Using position feedback via a worm gear system driven by a stepper motor and a
      precise rotary encoder, the actual angle of the compact UHV rotary feedthrough
      can be controlled with extremely high precision.

PMID- 22462960
TI  - Asymmetric-cut variable-incident-angle monochromator.
AB  - A novel asymmetric-cut variable-incident-angle monochromator was constructed and
      tested in 1997 at the Advanced Photon Source of Argonne National Laboratory. The
      monochromator was originally designed as a high heat load monochromator capable
      of handling 5-10 kW beams from a wiggler source. This was accomplished by
      spreading the x-ray beam out on the surface an asymmetric-cut crystal and by
      using liquid metal cooling of the first crystal. The monochromator turned out to
      be a highly versatile monochromator that could perform many different types of
      experiments. The monochromator consisted of two 18 degrees  asymmetrically cut Si
      crystals that could be rotated about 3 independent axes. The first stage (Phi)
      rotates the crystal around an axis perpendicular to the diffraction plane. This
      rotation changes the angle of the incident beam with the surface of the crystal
      without changing the Bragg angle. The second rotation (Psi) is perpendicular to
      the first and is used to control the shape of the beam footprint on the crystal.
      The third rotation (Theta) controls the Bragg angle. Besides the high heat load
      application, the use of asymmetrically cut crystals allows one to increase or
      decrease the acceptance angle for crystal diffraction of a monochromatic x-ray
      beam and allows one to increase or decrease the wavelength bandwidth of the
      diffraction of a continuum source like a bending-magnet beam or a normal x-ray
      tube source. When the monochromator is used in the doubly expanding mode, it is
      possible to expand the vertical size of the double-diffracted beam by a factor of
      10-15. When this was combined with a bending magnet source, it was possible to
      generate an 8 keV area beam, 16 mm wide by 26 mm high with a uniform intensity
      and parallel to 1.2 arc sec that could be applied in imaging experiments.

PMID- 22462961
TI  - Injector for scattering measurements on fully solvated biospecies.
AB  - We describe a liquid jet injector system developed to deliver fully solvated
      microscopic target species into a probe beam under either vacuum or ambient
      conditions. The injector was designed specifically for x-ray scattering studies
      of biological nanospecies using x-ray free electron lasers and third generation
      synchrotrons, but is of interest to any application in which microscopic samples
      must be delivered in a fully solvated state and with microscopic precision. By
      utilizing a gas dynamic virtual nozzle (GDVN) to generate a sample-containing
      liquid jet of diameter ranging from 300 nm to 20 MUm, the injector avoids the
      clogging problems associated in this size range with conventional Rayleigh jets.
      A differential pumping system incorporated into the injector shields the
      experimental chamber from the gas load of the GDVN, making the injector
      compatible with high vacuum systems. The injector houses a fiber-optically
      coupled pump laser to illuminate the jet for pump-probe experiments and a
      hermetically sealed microscope to observe the liquid jet for diagnostics and
      alignment during operation. This injector system has now been used during several
      experimental runs at the Linac Coherent Light Source. Recent refinements in GDVN
      design are also presented.

PMID- 22462962
TI  - Comparison of electrostatic fins with piezoelectric impact hammer techniques to
      extend impulse calibration range of a torsional thrust stand.
AB  - With the progression of high-power electric propulsion and high thrust-to-power
      propulsions system, thrust stand diagnostics require high-fidelity calibration
      systems that are accurate over a large-range of thrust levels. Multi-mode and
      variable I(sp) propulsion devices also require that a single stand be capable of
      measuring thrust from 10's of uNs to 100's of mNs. While the torsional thrust
      stand mechanic and diagnostics are capable of operating over such a large range,
      current pulsed calibration schemes are typically limited to a few orders of
      magnitude of dynamic range. In order to develop a stand with enough dynamic
      range, two separate calibration methods have been examined and compared to create
      a combined system. Electrostatic fin (ESF) and piezoelectric impact hammer (PIH)
      calibration systems were simultaneously tested on a large scale torsional thrust
      stand system. The use of the these two methods allowed the stand to be calibrated
      over four orders of magnitude, from 0.01 mNs to 750 mNs. The ESF system produced
      linear results within 0.52% from 0.01 mNs to 20 mNs, while the PIH system
      extended this calibration range from 10 mNs to 750 mNs with an error of 0.99%.
      The two calibration methods agreed within 4.51% over their overlapping range of
      10-20 mNs.

PMID- 22462963
TI  - Thin film measurement system for moving objects based on a laterally distributed
      linear variable filter spectrometer.
AB  - Instantaneous measurement of optical or geometrical parameters of thin layers is
      an ambitious aim in many industrial applications. These layers have a variety of
      use-cases, such as optical bandpassing, dielectric permittivity, or lubrication.
      Mostly, these layers are in motion due to the production process. In order to
      observe process parameters, the motion usually has to be disrupted. Thus, the
      increase of production time due to control purposes is an undesirable drawback of
      this otherwise suitable technique. In this publication, we present a solution to
      this particular drawback of most production process monitoring systems
      exemplarily for film thickness measurement. We show the realization of a
      measurement principle which has, to our knowledge, never been published before in
      this application. Therefore, we exploit the advantages of the combination of a
      linear variable filter with a complementary metal oxide semiconductor sensor
      array. By an apt readout sequence, this measurement system is able to measure
      transmission spectra while the target is in motion. We show that this measurement
      system is able to measure film thicknesses of objects in the range of several 100
      nm thickness at up to a velocity of 4 m/s. A reproducibility below 2 nm was
      acquired.

PMID- 22462964
TI  - A miniature cubic anvil apparatus for optical measurement under high pressure.
AB  - A miniature cubic anvil apparatus was developed for optical measurement on
      materials in a high-pressure space of 8-10 mm(3) under high pressure, and
      preliminary experiments were conducted to 3.6 GPa at room temperature with
      optical visual observation and ruby fluorescence measurement. In the apparatus, a
      cubic pressure medium was squeezed with six tungsten carbide anvils, which are
      driven with a pair of guide blocks by tightening four loading screws. Optical
      access on the sample was made through holes in axial anvils and the guide blocks
      as well as optical windows made of Al(2)O(3) single crystals embedded in the
      pressure medium. The apparatus is compact and light, ~53 mm in diameter and
      height and ~530 g in weight, and the features of the apparatus benefit easy
      application of the apparatus to various types of standard optical measurement
      systems. The optical measurement on the sample in the high-pressure space of 8-10
      mm(3) should greatly contribute to advancements of studies relevant to high
      pressure behaviors of materials.

PMID- 22462965
TI  - Development of autonomous gamma dose logger for environmental monitoring.
AB  - Continuous monitoring and archiving of background radiation levels in and around
      the nuclear installation is essential and the data would be of immense use during
      analysis of any untoward incidents. A portable Geiger Muller detector based
      autonomous gamma dose logger (AGDL) for environmental monitoring is indigenously
      designed and developed. The system operations are controlled by microcontroller
      (AT89S52) and the main features of the system are software data acquisition, real
      time LCD display of radiation level, data archiving at removable compact flash
      card. The complete system operates on 12 V battery backed up by solar panel and
      hence the system is totally portable and ideal for field use. The system has been
      calibrated with Co-60 source (8.1 MBq) at various source-detector distances. The
      system is field tested and performance evaluation is carried out. This paper
      covers the design considerations of the hardware, software architecture of the
      system along with details of the front-end operation of the autonomous gamma dose
      logger and the data file formats. The data gathered during field testing and
      inter comparison with GammaTRACER are also presented in the paper. AGDL has shown
      excellent correlation with energy fluence monitor tuned to identify (41)Ar,
      proving its utility for real-time plume tracking and source term estimation.

PMID- 22462966
TI  - Fast scanning mode and its realization in a scanning acoustic microscope.
AB  - The scanning speed of the two-dimensional stage dominates the efficiency of
      mechanical scanning measurement systems. This paper focused on a detailed
      scanning time analysis of conventional raster and spiral scan modes and then
      proposed two fast alternative scanning modes. Performed on a self-developed
      scanning acoustic microscope (SAM), the measured images obtained by using the
      conventional scan mode and fast scan modes are compared. The total scanning time
      is reduced by 29% of the two proposed fast scan modes. It will offer a better
      solution for high speed scanning without sacrificing the system stability, and
      will not introduce additional difficulties to the configuration of scanning
      measurement systems. They can be easily applied to the mechanical scanning
      measuring systems with different driving actuators such as piezoelectric, linear
      motor, dc motor, and so on. The proposed fast raster and square spiral scan modes
      are realized in SAM, but not specially designed for it. Therefore, they have
      universal adaptability and can be applied to other scanning measurement systems
      with two-dimensional mechanical scanning stages, such as atomic force microscope
      or scanning tunneling microscope.

PMID- 22462967
TI  - Note: Optical trigger device with sub-picosecond timing jitter and stability.
AB  - We are presenting the design, construction, and overall performance of the
      optical trigger device. This device generates an electrical signal synchronously
      to the detected ultra-short optical pulse. The device was designed for
      application in satellite laser ranging and laser time transfer experiments, time
      correlated photon counting and similar experiments, where picosecond timing
      resolution and detection delay stability are required. It consists of the
      ultrafast optical detector, signal discriminator, output pulse forming circuit,
      and output driver circuits. It was constructed as a single compact device to
      optimize their matching and maintain stability. The detector consists of an
      avalanche photodiode--both silicon and germanium types may be used to cover the
      wavelength range of 350-1550 nm. The analogue signal of this photodiode is sensed
      by the ultrafast comparator with 8 GHz bandwidth. The ps clock distribution
      circuit is used to generate the fast rise/fall time output pulses of pre-set
      length. The trigger device timing performance is excellent: the random component
      of the timing jitter is typically 880 fs, the temperature dependence of the
      detection delay was measured to be 370 fs/K. The systematic error contribution
      depends on the laser used and its stability. The sub-ps values have been obtained
      for various laser sources.

PMID- 22462968
TI  - Note: Experiments in hard x-ray chemistry: in situ production of molecular
      hydrogen and x-ray induced combustion.
AB  - We have successfully loaded H(2) into a diamond anvil cell at high pressure using
      the synchrotron x-ray induced decomposition of NH(3)BH(3). In a second set of
      studies, radiation-assisted release of O(2) from KCLO(3), H(2) release from
      NH(3)BH(3), and reaction of these gases in a mixture of the reactants to form
      liquid water using x-rays at ambient conditions was observed. Similar
      observations were made using a KCLO(3) and NaBH(4) mixture. Depending on reaction
      conditions, an explosive or far slower reaction producing water was observed.

PMID- 22462969
TI  - Note: High-speed optical tracking of a flying insect.
AB  - We developed a video recording system with the capability of tracking moving
      objects and used it to track the flight of an insect. The system consists of two
      galvano mirrors, which redirect the light coming from the object in two
      orthogonal directions toward a high-speed camera to capture the image. An
      additional high-speed camera, which views the same object through a beam splitter
      placed between one of the galvano mirrors and the observation camera, detects the
      position of the object. The mirror angle is controlled to maintain the position
      of the object at the center of the view, allowing the object to be tracked. In
      order to validate this system, images of a live fly in flight were recorded along
      a flight path that was much longer than the field of view of the stationary
      camera. A high-resolution video image of a rapidly moving live fly was
      successfully captured.

PMID- 22462970
TI  - Note: A large aperture four-mirror reflective wave-plate for high-intensity short
      pulse laser experiments.
AB  - We report on a four-mirror reflective wave-plate system based on a phase-shifting
      mirror (PSM) for a continuous variation of elliptical polarization without
      changing the beam position and direction. The system presented and characterized
      here can replace a conventional retardation plate providing all advantages of a
      PSM, such as high damage-threshold, large scalability, and low dispersion. This
      makes reflective wave-plates an ideal tool for ultra-high power laser
      applications.

PMID- 22462971
TI  - Note: Circuit design for direct current and alternating current electrochemical
      etching of scanning probe microscopy tips.
AB  - We present control circuits designed for electrochemically etching, reproducibly
      sharp STM probes. The design uses an Arduino UNO microcontroller to allow for
      both ac and dc operation, as well as a comparator driven shut-off that allows for
      etching to be stopped in 0.5-1 MUs. The Arduino allows the instrument to be
      customized to suit a wide variety of potential applications without significant
      changes to hardware. Data is presented for coarse chemical etching of 80:20
      platinum-iridium, tungsten, and nickel tips.

PMID- 22462972
TI  - Note: Programmable data acquisition system for research measurements from
      meteorological radiosondes.
AB  - A programmable data acquisition system to allow novel use of meteorological
      radiosondes for atmospheric science measurements is described. In its basic form
      it supports four analogue inputs at 16 bit resolution, and up to two further
      inputs at lower resolution, configurable instead for digital instruments. It also
      provides multiple instrument power supplies (+8 V, +16 V, +5 V, and -8 V) from
      the 9 V radiosonde battery. During a balloon flight encountering air temperatures
      from +17  degrees C to -66  degrees C, the worst case voltage drift in the 5 V
      unipolar digitisation circuitry was 20 mV. The system liberates a new range of
      low cost atmospheric research measurements, by utilising radiosondes routinely
      launched internationally for weather forecasting purposes. No additional
      receiving equipment is required. Comparisons between the specially instrumented
      and standard meteorological radiosondes show negligible effect of the additional
      instrumentation on the standard meteorological data.

PMID- 22462973
TI  - Note: A method to isolate and detect a large number of single molecules by
      microdroplet fluorescence spectroscopy.
AB  - A laser induced fluorescence system, in combination with a glass-frit nebulizer
      and a photo-voltaic cell detector, is described for single molecule detection.
      The glass-frit nebulizer continuously generates a large number of droplets with
      an average droplet size of three micrometers in diameter. Rhodamine 6G molecules
      were detected at the 10(-12) M level. Concentrations 10(-12)-10(-10) M would
      provide mostly single molecules (0, 1, 2, 3, ...) in the individual droplets, as
      determined by Poisson distribution.

PMID- 22462974
TI  - Note: A scanning electron microscope sample holder for bidirectional
      characterization of atomic force microscope probe tips.
AB  - A novel sample holder that enables atomic force microscopy (AFM) tips to be
      mounted inside a scanning electron microscopy (SEM) for the purpose of
      characterizing the AFM tips is described. The holder provides quick and easy
      handling of tips by using a spring clip to hold them in place. The holder can
      accommodate two tips simultaneously in two perpendicular orientations, allowing
      both top and side view imaging of the tips by the SEM.

PMID- 22462975
TI  - Comment on "Print your atomic force microscope" [Rev. Sci. Instrum. 78, 075105
      (2007)].
AB  - The paper of Kuhner et al. [Rev. Sci. Instrum. 78, 075105 (2007)], presents a
      sound realization of a very nice idea. Namely, to design and prepare (via rapid
      prototyping) a custom head for atomic force microscope (AFM). Custom AFM heads
      are essential for various applications, which include the AFM force spectroscopy
      modes and convenient AFM coupling with other techniques. Our comment concerns the
      deflection data for a thermally driven AFM cantilever obtained by Kuhner et al.
      using their AFM setup (Figure 3 therein). The results of Kuhner et al. imply that
      a thermally excited AFM cantilever vibrates with aberrantly large amplitudes.
      Namely, the deflection noise amplitudes for the MLCT-D cantilever are 60-100
      times larger than what is typically observed in our lab and by others. As we
      argue, the author's mistake is likely attributed to an improper usage of the AFM
      bandwidth. We explain the necessary correction and discuss the issue of bandwidth
      for the AFM force spectroscopy measurements.

PMID- 22462977
TI  - The impact of awareness on epidemic spreading in networks.
AB  - We explore the impact of awareness on epidemic spreading through a population
      represented by a scale-free network. Using a network mean-field approach, a
      mathematical model for epidemic spreading with awareness reactions is proposed
      and analyzed. We focus on the role of three forms of awareness including local,
      global, and contact awareness. By theoretical analysis and simulation, we show
      that the global awareness cannot decrease the likelihood of an epidemic outbreak
      while both the local awareness and the contact awareness can. Also, the influence
      degree of the local awareness on disease dynamics is closely related with the
      contact awareness.

PMID- 22462978
TI  - Multiscale dynamics in communities of phase oscillators.
AB  - We investigate the dynamics of systems of many coupled phase oscillators with
      heterogeneous frequencies. We suppose that the oscillators occur in M groups.
      Each oscillator is connected to other oscillators in its group with "attractive"
      coupling, such that the coupling promotes synchronization within the group. The
      coupling between oscillators in different groups is "repulsive," i.e., their
      oscillation phases repel. To address this problem, we reduce the governing
      equations to a lower-dimensional form via the ansatz of Ott and Antonsen, Chaos
      18, 037113 (2008). We first consider the symmetric case where all group
      parameters are the same, and the attractive and repulsive coupling are also the
      same for each of the M groups. We find a manifold L of neutrally stable
      equilibria, and we show that all other equilibria are unstable. For M >= 3, L has
      dimension M - 2, and for M = 2, it has dimension 1. To address the general
      asymmetric case, we then introduce small deviations from symmetry in the group
      and coupling parameters. Doing a slow/fast timescale analysis, we obtain slow
      time evolution equations for the motion of the M groups on the manifold L. We use
      these equations to study the dynamics of the groups and compare the results with
      numerical simulations.

PMID- 22462979
TI  - Resonance phenomena and long-term chaotic advection in volume-preserving systems.
AB  - Creating chaotic advection is the most efficient strategy to achieve mixing on
      microscale or in very viscous fluids. In this paper, we present a quantitative
      theory of the long-time resonant mixing in 3D near-integrable flows. We use the
      flow between two coaxial elliptic counter-rotating cylinders as a demonstrative
      model, where multiple scatterings on resonance result in mixing by causing the
      jumps of adiabatic invariants. We improve the existing estimates of the width of
      the mixing domain. We show that the resulting mixing both on short and long time
      scales can be described in terms of a single diffusion-type equation with a
      diffusion coefficient depending on the averaged effect of multiple passages
      through resonances. We discuss the exact location of the boundaries of the
      chaotic domain and show how it affects the properties of mixing.

PMID- 22462980
TI  - Propagation of spiking regularity and double coherence resonance in feedforward
      networks.
AB  - We investigate the propagation of spiking regularity in noisy feedforward
      networks (FFNs) based on FitzHugh-Nagumo neuron model systematically. It is found
      that noise could modulate the transmission of firing rate and spiking regularity.
      Noise-induced synchronization and synfire-enhanced coherence resonance are also
      observed when signals propagate in noisy multilayer networks. It is interesting
      that double coherence resonance (DCR) with the combination of synaptic input
      correlation and noise intensity is finally attained after the processing layer by
      layer in FFNs. Furthermore, inhibitory connections also play essential roles in
      shaping DCR phenomena. Several properties of the neuronal network such as noise
      intensity, correlation of synaptic inputs, and inhibitory connections can serve
      as control parameters in modulating both rate coding and the order of temporal
      coding.

PMID- 22462981
TI  - Transcripts: an algebraic approach to coupled time series.
AB  - Ordinal symbolic dynamics is based on ordinal patterns. Its tools include
      permutation entropy (in metric and topological versions), forbidden patterns, and
      a number of mathematical results that make this sort of symbolic dynamics
      appealing both for theoreticians and practitioners. In particular, ordinal
      symbolic dynamics is robust against observational noise and can be implemented
      with low computational cost, which explains its increasing popularity in time
      series analysis. In this paper, we study the perhaps less exploited aspect so far
      of ordinal patterns: their algebraic structure. In a first part, we revisit the
      concept of transcript between two symbolic representations, generalize it to N
      representations, and derive some general properties. In a second part, we use
      transcripts to define two complexity indicators of coupled dynamics. Their
      performance is tested with numerical and real world data.

PMID- 22462982
TI  - Saddle-point solutions and grazing bifurcations in an impacting system.
AB  - This paper focuses on the intricate relationship between smooth and nonsmooth
      phenomena in an impacting system. In particular a boundary saddle-point solution,
      that is born in a nonsmooth fold, is analysed. Accessible boundary saddle-point
      solutions play a key role in determining the global dynamics of a system and here
      we will show how grazing bifurcations can affect their existence.

PMID- 22462983
TI  - Multiscale characterization of recurrence-based phase space networks constructed
      from time series.
AB  - Recently, a framework for analyzing time series by constructing an associated
      complex network has attracted significant research interest. One of the
      advantages of the complex network method for studying time series is that complex
      network theory provides a tool to describe either important nodes, or structures
      that exist in the networks, at different topological scale. This can then provide
      distinct information for time series of different dynamical systems. In this
      paper, we systematically investigate the recurrence-based phase space network of
      order k that has previously been used to specify different types of dynamics in
      terms of the motif ranking from a different perspective. Globally, we find that
      the network size scales with different scale exponents and the degree
      distribution follows a quasi-symmetric bell shape around the value of 2k with
      different values of degree variance from periodic to chaotic Rossler systems.
      Local network properties such as the vertex degree, the clustering coefficients
      and betweenness centrality are found to be sensitive to the local stability of
      the orbits and hence contain complementary information.

PMID- 22462985
TI  - Analytical properties of horizontal visibility graphs in the Feigenbaum scenario.
AB  - Time series are proficiently converted into graphs via the horizontal visibility
      (HV) algorithm, which prompts interest in its capability for capturing the nature
      of different classes of series in a network context. We have recently shown [B.
      Luque et al., PLoS ONE 6, 9 (2011)] that dynamical systems can be studied from a
      novel perspective via the use of this method. Specifically, the period-doubling
      and band-splitting attractor cascades that characterize unimodal maps transform
      into families of graphs that turn out to be independent of map nonlinearity or
      other particulars. Here, we provide an in depth description of the HV treatment
      of the Feigenbaum scenario, together with analytical derivations that relate to
      the degree distributions, mean distances, clustering coefficients, etc.,
      associated to the bifurcation cascades and their accumulation points. We describe
      how the resultant families of graphs can be framed into a renormalization group
      scheme in which fixed-point graphs reveal their scaling properties. These fixed
      points are then re-derived from an entropy optimization process defined for the
      graph sets, confirming a suggested connection between renormalization group and
      entropy optimization. Finally, we provide analytical and numerical results for
      the graph entropy and show that it emulates the Lyapunov exponent of the map
      independently of its sign.

PMID- 22462984
TI  - Fractal variability: an emergent property of complex dissipative systems.
AB  - The patterns of variation of physiologic parameters, such as heart and
      respiratory rate, and their alteration with age and illness have long been under
      investigation; however, the origin and significance of scale-invariant fractal
      temporal structures that characterize healthy biologic variability remain
      unknown. Quite independently, atmospheric and planetary scientists have led
      breakthroughs in the science of non-equilibrium thermodynamics. In this paper, we
      aim to provide two novel hypotheses regarding the origin and etiology of both the
      degree of variability and its fractal properties. In a complex dissipative
      system, we hypothesize that the degree of variability reflects the adaptability
      of the system and is proportional to maximum work output possible divided by
      resting work output. Reductions in maximal work output (and oxygen consumption)
      or elevation in resting work output (or oxygen consumption) will thus reduce
      overall degree of variability. Second, we hypothesize that the fractal nature of
      variability is a self-organizing emergent property of complex dissipative
      systems, precisely because it enables the system's ability to optimally dissipate
      energy gradients and maximize entropy production. In physiologic terms, fractal
      patterns in space (e.g., fractal vasculature) or time (e.g., cardiopulmonary
      variability) optimize the ability to deliver oxygen and clear carbon dioxide and
      waste. Examples of falsifiability are discussed, along with the need to further
      define necessary boundary conditions. Last, as our focus is bedside utility,
      potential clinical applications of this understanding are briefly discussed. The
      hypotheses are clinically relevant and have potential widespread scientific
      relevance.

PMID- 22462986
TI  - Theoretical analysis of multiplicative-noise-induced complete synchronization in
      global coupled dynamical network.
AB  - In this paper, based on the theory of stochastic differential equation, we study
      the effect of noise on the synchronization of global coupled dynamical network,
      when noise presents in coupling term. The theoretical result shows that noise can
      really induce synchronization. To verify the theoretical result, Cellular Neural
      Network neural model and Rossler-like system are performed as numerical examples.

PMID- 22462987
TI  - Using time-delayed mutual information to discover and interpret temporal
      correlation structure in complex populations.
AB  - This paper addresses how to calculate and interpret the time-delayed mutual
      information (TDMI) for a complex, diversely and sparsely measured, possibly non
      stationary population of time-series of unknown composition and origin. The
      primary vehicle used for this analysis is a comparison between the time-delayed
      mutual information averaged over the population and the time-delayed mutual
      information of an aggregated population (here, aggregation implies the population
      is conjoined before any statistical estimates are implemented). Through the use
      of information theoretic tools, a sequence of practically implementable
      calculations are detailed that allow for the average and aggregate time-delayed
      mutual information to be interpreted. Moreover, these calculations can also be
      used to understand the degree of homo or heterogeneity present in the population.
      To demonstrate that the proposed methods can be used in nearly any situation, the
      methods are applied and demonstrated on the time series of glucose measurements
      from two different subpopulations of individuals from the Columbia University
      Medical Center electronic health record repository, revealing a picture of the
      composition of the population as well as physiological features.

PMID- 22462988
TI  - Vibrational resonance in Duffing systems with fractional-order damping.
AB  - The phenomenon of vibrational resonance (VR) is investigated in over- and under
      damped Duffing systems with fractional-order damping. It is found that the
      factional-order damping can induce change in the number of the steady stable
      states and then lead to single- or double-resonance behavior. Compared with
      vibrational resonance in the ordinary systems, the following new results are
      found in the fractional-order systems. (1) In the overdamped system with double
      well potential and ordinary damping, there is only one kind of single-resonance,
      whereas there are double-resonance and two kinds of single-resonance for the case
      of fractional-order damping. The necessary condition for these new resonance
      behaviors is the value of the fractional-order satisfies alpha > 1. (2) In the
      overdamped system with single-well potential and ordinary damping, there is no
      resonance, whereas there is a single-resonance for the case of fractional-order
      damping. The necessary condition for the new result is alpha > 1. (3) In the
      underdamped system with double-well potential and ordinary damping, there are
      double-resonance and one kind of single-resonance, whereas there are double
      resonance and two kinds of single-resonance for the case of  fractional-order
      damping. The necessary condition for the new single-resonance is alpha < 1. (4)
      In the underdamped system with single-well potential, there is at most a single
      resonance existing for both the cases of ordinary and fractional-order damping.
      In the underdamped systems, varying the value of the fractional-order is
      equivalent to change the damping parameter for some cases.

PMID- 22462989
TI  - Symmetry chaotic attractors and bursting dynamics of semiconductor lasers
      subjected to optical injection.
AB  - This paper presents the nonlinear dynamics and bifurcations of optically injected
      semiconductor lasers in the frame of relative high injection strength. The
      behavior of the system is explored by means of bifurcation diagrams; however, the
      exact nature of the involved dynamics is well described by a detailed study of
      the dynamics evolutions as a function of the effective gain coefficient. As
      results, we notice the different types of symmetry chaotic attractors with the
      riddled basins, supercritical pitchfork and Hopf bifurcations, crisis of
      attractors, instability of chaos, symmetry breaking and restoring bifurcations,
      and the phenomena of the bursting behavior as well as two connected parts of the
      same chaotic attractor which merge in a periodic orbit.

PMID- 22462990
TI  - Multistability of twisted states in non-locally coupled Kuramoto-type models.
AB  - A ring of N identical phase oscillators with interactions between L-nearest
      neighbors is considered, where L ranges from 1 (local coupling) to N/2 (global
      coupling). The coupling function is a simple sinusoid, as in the Kuramoto model,
      but with a minus sign which has a profound influence on its behavior. Without the
      limitation of the generality, the frequency of the free-running oscillators can
      be set to zero. The resulting system is of gradient type, and therefore, all its
      solutions converge to an equilibrium point. All so-called q-twisted states, where
      the phase difference between neighboring oscillators on the ring is 2piq/N, are
      equilibrium points, where q is an integer. Their stability in the limit N ->
      infinity is discussed along the line of Wiley et al. [Chaos 16, 015103 (2006)] In
      addition, we prove that when a twisted state is asymptotically stable for the
      infinite system, it is also asymptotically stable for sufficiently large N. Note
      that for smaller N, the same q-twisted states may become unstable and other q
      twisted states may become stable. Finally, the existence of additional
      equilibrium states, called here multi-twisted states, is shown by numerical
      simulation. The phase difference between neighboring oscillators is approximately
      2piq/N in one sector of the ring, -2piq/N in another sector, and it has
      intermediate values between the two sectors. Our numerical investigation suggests
      that the number of different stable multi-twisted states grows exponentially as N
      -> infinity. It is possible to interpret the equilibrium points of the coupled
      phase oscillator network as trajectories of a discrete-time translational
      dynamical system where the space-variable (position on the ring) plays the role
      of time. The q-twisted states are then fixed points, and the multi-twisted states
      are periodic solutions of period N that are close to a heteroclinic cycle. Due to
      the apparently exponentially fast growing number of such stable periodic
      solutions, the system shows spatial chaos as N -> infinity.

PMID- 22462991
TI  - Geometric and dynamic perspectives on phase-coherent and noncoherent chaos.
AB  - Statistically distinguishing between phase-coherent and noncoherent chaotic
      dynamics from time series is a contemporary problem in nonlinear sciences. In
      this work, we propose different measures based on recurrence properties of
      recorded trajectories, which characterize the underlying systems from both
      geometric and dynamic viewpoints. The potentials of the individual measures for
      discriminating phase-coherent and noncoherent chaotic oscillations are discussed.
      A detailed numerical analysis is performed for the chaotic Rossler system, which
      displays both types of chaos as one control parameter is varied, and the Mackey
      Glass system as an example of a time-delay system with noncoherent chaos. Our
      results demonstrate that especially geometric measures from recurrence network
      analysis are well suited for tracing transitions between spiral- and screw-type
      chaos, a common route from phase-coherent to noncoherent chaos also found in
      other nonlinear oscillators. A detailed explanation of the observed behavior in
      terms of attractor geometry is given.

PMID- 22462992
TI  - Long-range interactions between adjacent and distant bases in a DNA and their
      impact on the ribonucleic acid polymerase-DNA dynamics.
AB  - When an inhomogeneous RNA-polymerase (RNAP) binds to an inhomogeneous DNA at the
      physiological temperature, we propose a spin-like model of DNA nonlinear dynamics
      with long-range interactions (LRI) between adjacent and distant base pairs to
      study RNAP-DNA dynamics. Using Holstein-Primakoff's representation and Glauber's
      coherent state representation, we show that the model equation is a completely
      integrable nonlinear Schrodinger equation whose dispersive coefficient depends on
      LRI's parameter. Inhomogeneities have introduced perturbation terms in the
      equation of motion of RNAP-DNA dynamics. Considering the homogeneous part of that
      equation, a detailed study of the solution shows that the number of base pairs
      which form the bubble, the height, and the width of that bubble depend on the
      long-range parameter. The results of the perturbation analysis show that the
      inhomogeneities due to the DNA and RNAP structures do not alter the velocity and
      amplitude of the soliton, but introduce some fluctuations in the localized region
      of the soliton. The events that happen in the present study may represent binding
      of an RNAP to a promoter site in the DNA during the transcription process.

PMID- 22462993
TI  - The structure and resilience of financial market networks.
AB  - Financial markets can be viewed as a highly complex evolving system that is very
      sensitive to economic instabilities. The complex organization of the market can
      be represented in a suitable fashion in terms of complex networks, which can be
      constructed from stock prices such that each pair of stocks is connected by a
      weighted edge that encodes the distance between them. In this work, we propose an
      approach to analyze the topological and dynamic evolution of financial networks
      based on the stock correlation matrices. An entropy-related measurement is
      adopted to quantify the robustness of the evolving financial market organization.
      It is verified that the network topological organization suffers strong variation
      during financial instabilities and the networks in such periods become less
      robust. A statistical robust regression model is proposed to quantity the
      relationship between the network structure and resilience. The obtained
      coefficients of such model indicate that the average shortest path length is the
      measurement most related to network resilience coefficient. This result indicates
      that a collective behavior is observed between stocks during financial crisis.
      More specifically, stocks tend to synchronize their price evolution, leading to a
      high correlation between pair of stock prices, which contributes to the increase
      in distance between them and, consequently, decrease the network resilience.

PMID- 22462994
TI  - Alternation of regular and chaotic dynamics in a simple two-degree-of-freedom
      system with nonlinear inertial coupling.
AB  - We show that nonlinear inertial coupling between a linear oscillator and an
      eccentric rotator can lead to very interesting interchanges between regular and
      chaotic dynamical behavior. Indeed, we show that this model demonstrates rather
      unusual behavior from the viewpoint of nonlinear dynamics. Specifically, at a
      discrete set of values of the total energy, the Hamiltonian system exhibits non
      conventional nonlinear normal modes, whose shape is determined by phase locking
      of rotatory and oscillatory motions of the rotator at integer ratios of
      characteristic frequencies. Considering the weakly damped system, resonance
      capture of the dynamics into the vicinity of these modes brings about regular
      motion of the system. For energy levels far from these discrete values, the
      motion of the system is chaotic. Thus, the succession of resonance captures and
      escapes by a discrete set of the normal modes causes a sequence of transitions
      between regular and chaotic behavior, provided that the damping is sufficiently
      small. We begin from the Hamiltonian system and present a series of Poincare
      sections manifesting the complex structure of the phase space of the considered
      system with inertial nonlinear coupling. Then an approximate analytical
      description is presented for the non-conventional nonlinear normal modes. We
      confirm the analytical results by numerical simulation and demonstrate the
      alternate transitions between regular and chaotic dynamics mentioned above. The
      origin of the chaotic behavior is also discussed.

PMID- 22462996
TI  - Stabilization of chaos systems described by nonlinear fractional-order polytopic
      differential inclusion.
AB  - In this paper, sliding mode control is utilized for stabilization of a particular
      class of nonlinear polytopic differential inclusion systems with fractional-order
      0 < q < 1. This class of fractional order differential inclusion systems is used
      to model physical chaotic fractional order Chen and Lu systems. By defining a
      sliding surface with fractional integral formula, exploiting the concept of the
      state space norm, and obtaining sufficient conditions for stability of the
      sliding surface, a special feedback law is presented which enables the system
      states to reach the sliding surface and consequently creates a sliding mode
      control. Finally, simulation results are used to illustrate the effectiveness of
      the proposed method.

PMID- 22462995
TI  - Finger tapping movements of Parkinson's disease patients automatically rated
      using nonlinear delay differential equations.
AB  - Parkinson's disease is a degenerative condition whose severity is assessed by
      clinical observations of motor behaviors. These are performed by a neurological
      specialist through subjective ratings of a variety of movements including 10-s
      bouts of repetitive finger-tapping movements. We present here an algorithmic
      rating of these movements which may be beneficial for uniformly assessing the
      progression of the disease. Finger-tapping movements were digitally recorded from
      Parkinson's patients and controls, obtaining one time series for every 10 s bout.
      A nonlinear delay differential equation, whose structure was selected using a
      genetic algorithm, was fitted to each time series and its coefficients were used
      as a six-dimensional numerical descriptor. The algorithm was applied to time
      series from two different groups of Parkinson's patients and controls. The
      algorithmic scores compared favorably with the unified Parkinson's disease rating
      scale scores, at least when the latter adequately matched with ratings from the
      Hoehn and Yahr scale. Moreover, when the two sets of mean scores for all patients
      are compared, there is a strong (r = 0.785) and significant (p<0.0015)
      correlation between them.

PMID- 22462997
TI  - Bifurcation phenomena in an impulsive model of non-basal testosterone regulation.
AB  - Complex nonlinear dynamics in a recent mathematical model of non-basal
      testosterone regulation are investigated. In agreement with biological evidence,
      the pulsatile (non-basal) secretion of testosterone is modeled by frequency and
      amplitude modulated feedback. It is shown that, in addition to already known
      periodic motions with one and two pulses in the least period of a closed-loop
      system solution, cycles of higher periodicity and chaos are present in the model
      in hand. The broad range of exhibited dynamic behaviors makes the model highly
      promising in model-based signal processing of hormone data.

PMID- 22462998
TI  - Neural networks and chaos: construction, evaluation of chaotic networks, and
      prediction of chaos with multilayer feedforward networks.
AB  - Many research works deal with chaotic neural networks for various fields of
      application. Unfortunately, up to now, these networks are usually claimed to be
      chaotic without any mathematical proof. The purpose of this paper is to
      establish, based on a rigorous theoretical framework, an equivalence between
      chaotic iterations according to Devaney and a particular class of neural
      networks. On the one hand, we show how to build such a network, on the other
      hand, we provide a method to check if a neural network is a chaotic one. Finally,
      the ability of classical feedforward multilayer perceptrons to learn sets of data
      obtained from a dynamical system is regarded. Various boolean functions are
      iterated on finite states. Iterations of some of them are proven to be chaotic as
      it is defined by Devaney. In that context, important differences occur in the
      training process, establishing with various neural networks that chaotic
      behaviors are far more difficult to learn.

PMID- 22462999
TI  - Nonlinear dynamics of the membrane potential of a bursting pacemaker cell.
AB  - This article presents the results of an exploration of one two-parameter space of
      the Chay model of a cell excitable membrane. There are two main regions: a
      peripheral one, where the system dynamics will relax to an equilibrium point, and
      a central one where the expected dynamics is oscillatory. In the second region,
      we observe a variety of self-sustained oscillations including periodic
      oscillation, as well as bursting dynamics of different types. These oscillatory
      dynamics can be observed as periodic oscillations with different periodicities,
      and in some cases, as chaotic dynamics. These results, when displayed in
      bifurcation diagrams, result in complex bifurcation structures, which have been
      suggested as relevant to understand biological cell signaling.

PMID- 22463000
TI  - Exponential synchronization of stochastic neural networks with leakage delay and
      reaction-diffusion terms via periodically intermittent control.
AB  - We explore the issue of integrating leakage delay, stochastic noise perturbation,
      and  reaction-diffusion effects into the study of synchronization for neural
      networks with  time-varying delays. By using Lyapunov stability theory and
      stochastic analysis approaches, a periodically intermittent controller is
      proposed to guarantee the exponential synchronization of proposed coupled neural
      networks based on p-norm. Some existing results are improved and extended. The
      usefulness and superiority of our theoretical results are illustrated by a
      numerical example.

PMID- 22463001
TI  - Conedy: a scientific tool to investigate complex network dynamics.
AB  - We present Conedy, a performant scientific tool to numerically investigate
      dynamics on complex networks. Conedy allows to create networks and provides
      automatic code generation and compilation to ensure performant treatment of
      arbitrary node dynamics. Conedy can be interfaced via an internal script
      interpreter or via a Python module.

PMID- 22463002
TI  - A class of Lorenz-like systems.
AB  - The transformation of a three-dimensional dynamical system to its differential
      model can be used to identify different nonlinear dynamical systems that share
      the same time series of one of its variables. This transformation then can be
      used to find classes of nonlinear dynamical systems with similar dynamical
      behavior.

PMID- 22463003
TI  - Multi-parameter identification from scalar time series generated by a Malkus
      Lorenz water wheel.
AB  - We address the issue of multi-parameter estimation from scalar outputs of chaotic
      systems, using the dynamics of a Malkus water wheel and simulations of the
      corresponding Lorenz-equations model as an example. We discuss and compare two
      estimators: one is based on a globally convergent adaptive observer and the
      second is an extended Kalman filter (EKF). Both estimators can identify all three
      unknown parameters of the model. We find that the estimated parameter values are
      in agreement with those obtained from direct measurements on the experimental
      system. In addition, we explore the question of how to distinguish the impact of
      noise from those of model imperfections by investigating a model generalization
      and the use of uncertainty estimates provided by the extended Kalman filter.
      Although we are able to exclude asymmetric inflow as a possible unmodeled effect,
      our results indicate that the Lorenz-equations do not perfectly describe the
      water wheel dynamics.

PMID- 22463004
TI  - Computing Lagrangian coherent structures from their variational theory.
AB  - Using the recently developed variational theory of hyperbolic Lagrangian coherent
      structures (LCSs), we introduce a computational approach that renders attracting
      and repelling LCSs as smooth, parametrized curves in two-dimensional flows. The
      curves are obtained as trajectories of an autonomous ordinary differential
      equation for the tensor lines of the Cauchy-Green strain tensor. This approach
      eliminates false positives and negatives in LCS detection by separating true
      exponential stretching from shear in a frame-independent fashion. Having an
      explicitly parametrized form for hyperbolic LCSs also allows for their further in
      depth analysis and accurate advection as material lines. We illustrate these
      results on a kinematic model flow and on a direct numerical simulation of two
      dimensional turbulence.

PMID- 22463005
TI  - Delay-driven spatial patterns in a plankton allelopathic system.
AB  - Spatial patterns have received considerable attention in the physical,
      biological, and social sciences. Generally speaking, time delay is a prevailing
      phenomenon in aquatic environments, since the production of allelopathic
      substance by competitive species is not instantaneous, but mediated by some time
      lag required for maturity of species. A natural question is how delay affects the
      spatial patterns. Here, we consider a delayed plankton allelopathic system
      consisting of two competitive species and analytically investigate how the time
      delay affects the stability and spatial patterns. Based upon a stability
      analysis, we demonstrate that the delay can induce spatial patterns under some
      conditions. Moreover, by use of a series of numerical simulations performed with
      a finite difference scheme, we show that the delay plays an important role on
      pattern selection.

PMID- 22463006
TI  - Strange beta: an assistance system for indoor rock climbing route setting.
AB  - This paper applies the mathematics of chaos to the task of designing indoor rock
      climbing routes. Chaotic variation has been used to great advantage on music and
      dance, but the challenges here are quite different, beginning with the
      representation. We present a formalized system for transcribing rock climbing
      problems and then describe a variation generator that is designed to support
      human route-setters in designing new and interesting climbing problems. This
      variation generator, termed strange beta, uses chaos to introduce novelty. We
      validated this approach with a large blinded study in a commercial climbing gym,
      in cooperation with experienced climbers and expert route setters. The results
      show that strange beta can help a human setter produce routes that are at least
      as good as, and in some cases better than, those produced in the traditional
      manner.

PMID- 22463007
TI  - Time-independent description of rapidly driven systems in the presence of
      friction: multiple scale perturbation approach.
AB  - The dynamics of a classical system driven by a rapidly oscillating field (with
      frequency omega) in the presence of friction has been investigated using the
      multiple scale perturbation theory (MSPT). By exploiting the idea of separation
      of time scales, the slow motion has been computed in a systematic expansion in
      the inverse of omega to the order omega(-3). This perturbation series can be
      viewed as a generalization of the calculation presented by Landau and Lifshitz
      for Kapitza's pendulum (where the point of suspension is moved periodically) in
      the presence of friction. The radiation induced dynamics of the system is found
      to be described by an effective time-independent potential with friction that
      controls the slow motion. The explicit appearance of friction in our computed
      effective potential is a manifestation of the dynamical effect due to the fast
      motion. The present study demonstrates that MSPT can be used to understand and
      predict the classical dynamics of a driven system in the presence of friction.

PMID- 22463008
TI  - Chimeras in random non-complete networks of phase oscillators.
AB  - We consider the simplest network of coupled non-identical phase oscillators
      capable of displaying a "chimera" state (namely, two subnetworks with strong
      coupling within the subnetworks and weaker coupling between them) and
      systematically investigate the effects of gradually removing connections within
      the network, in a random but systematically specified way. We average over
      ensembles of networks with the same random connectivity but different intrinsic
      oscillator frequencies and derive ordinary differential equations (ODEs), whose
      fixed points describe a typical chimera state in a representative network of
      phase oscillators. Following these fixed points as parameters are varied we find
      that chimera states are quite sensitive to such random removals of connections,
      and that oscillations of chimera states can be either created or suppressed in
      apparent bifurcation points, depending on exactly how the connections are
      gradually removed.

PMID- 22463009
TI  - Long-term fluctuations in globally coupled phase oscillators with general
      coupling: finite size effects.
AB  - We investigate the diffusion coefficient of the time integral of the Kuramoto
      order parameter in globally coupled nonidentical phase oscillators. This
      coefficient represents the deviation of the time integral of the order parameter
      from its mean value on the sample average. In other words, this coefficient
      characterizes long-term fluctuations of the order parameter. For a system of N
      coupled oscillators, we introduce a statistical quantity D, which denotes the
      product of N and the diffusion coefficient. We study the scaling law of D with
      respect to the system size N. In other well-known models such as the Ising model,
      the scaling property of D is D~O(1) for both coherent and incoherent regimes
      except for the transition point. In contrast, in the globally coupled phase
      oscillators, the scaling law of D is different for the coherent and incoherent
      regimes: D~O(1/N(a)) with a certain constant a>0 in the coherent regime and
      D~O(1) in the incoherent regime. We demonstrate that these scaling laws hold for
      several representative coupling schemes.

PMID- 22463010
TI  - Spatiotemporal chaos in the dynamics of buoyantly and diffusively unstable
      chemical fronts.
AB  - Nonlinear dynamics resulting from the interplay between diffusive and buoyancy
      driven Rayleigh-Taylor (RT) instabilities of autocatalytic traveling fronts are
      analyzed numerically for various values of the relevant parameters. These are the
      Rayleigh numbers of the reactant A and autocatalytic product B solutions as well
      as the ratio D=D(B)/D(A) between the diffusion coefficients of the two key
      chemical species. The interplay between the coarsening dynamics characteristic of
      the RT instability and the constant short wavelength modulation of the diffusive
      instability can lead in some regimes to complex dynamics dominated by irregular
      succession of birth and death of fingers. By using spectral entropy measurements,
      we characterize the transition between order and spatial disorder in this system.
      The analysis of the power spectrum and autocorrelation function, moreover,
      identifies similarities between the various spatial patterns. The contribution of
      the diffusive instability to the complex dynamics is discussed.

PMID- 22463011
TI  - Period adding cascades: experiment and modeling in air bubbling.
AB  - Period adding cascades have been observed experimentally/numerically in the
      dynamics of neurons and pancreatic cells, lasers, electric circuits, chemical
      reactions, oceanic internal waves, and also in air bubbling. We show that the
      period adding cascades appearing in bubbling from a nozzle submerged in a viscous
      liquid can be reproduced by a simple model, based on some hydrodynamical
      principles, dealing with the time evolution of two variables, bubble position and
      pressure of the air chamber, through a system of differential equations with a
      rule of detachment based on force balance. The model further reduces to an
      iterating one-dimensional map giving the pressures at the detachments, where time
      between bubbles come out as an observable of the dynamics. The model has not only
      good agreement with experimental data, but is also able to predict the influence
      of the main parameters involved, like the length of the hose connecting the air
      supplier with the needle, the needle radius and the needle length.

PMID- 22463012
TI  - A heuristic method for identifying chaos from frequency content.
AB  - The sign of the largest Lyapunov exponent is the fundamental indicator of chaos
      in a dynamical system. However, although the extraction of Lyapunov exponents can
      be accomplished with (necessarily noisy) the experimental data, this is still a
      relatively data-intensive and sensitive endeavor. This paper presents an
      alternative pragmatic approach to identifying chaos using response frequency
      characteristics and extending the concept of the spectrogram. The method is shown
      to work well on both experimental and simulated time series.

PMID- 22463013
TI  - Dynamics and transport in mean-field coupled, many degrees-of-freedom, area
      preserving nontwist maps.
AB  - Area-preserving nontwist maps, i.e., maps that violate the twist condition, arise
      in the study of degenerate Hamiltonian systems for which the standard version of
      the Kolmogorov-Arnold-Moser (KAM) theorem fails to apply. These maps have found
      applications in several areas including plasma physics, fluid mechanics, and
      condensed matter physics. Previous work has limited attention to maps in 2
      dimensional phase space. Going beyond these studies, in this paper, we study
      nontwist maps with many-degrees-of-freedom. We propose a model in which the
      different degrees of freedom are coupled through a mean-field that evolves self
      consistently. Based on the linear stability of period-one and period-two orbits
      of the coupled maps, we construct coherent states in which the degrees of freedom
      are synchronized and the mean-field stays nearly fixed. Nontwist systems exhibit
      global bifurcations in phase space known as separatrix reconnection. Here, we
      show that the mean-field coupling leads to dynamic, self-consistent reconnection
      in which transport across invariant curves can take place in the absence of chaos
      due to changes in the topology of the separatrices. In the context of self
      consistent chaotic transport, we study two novel problems: suppression of
      diffusion and breakup of the shearless curve. For both problems, we construct a
      macroscopic effective diffusion model with time-dependent diffusivity. Self
      consistent transport near criticality is also studied, and it is shown that the
      threshold for global transport as function of time is a fat-fractal Cantor-type
      set.

PMID- 22463014
TI  - Spontaneous soliton generation in the higher order Korteweg-de Vries equations on
      the half-line.
AB  - Some new effects in the soliton dynamics governed by higher order Korteweg-de
      Vries (KdV) equations are discussed based on the exact explicit solutions of the
      equations on the positive half-line. The solutions describe the process of
      generation of a soliton that occurs without boundary forcing and on the steady
      state background: the boundary conditions remain constant and the initial
      distribution is a steady state solution of the problem. The time moment when the
      soliton generation starts is not determined by the parameters present in the
      problem formulation, the additional parameters imbedded into the solution are
      needed to determine that moment. The equations found capable of describing those
      effects are the integrable Sawada-Kotera equation and the KdV-Kaup-Kupershmidt
      (KdV-KK) equation which, albeit not proven to be integrable, possesses multi
      soliton solutions.

PMID- 22463015
TI  - Network extreme eigenvalue: from mutimodal to scale-free networks.
AB  - The extreme eigenvalues of adjacency matrices are important indicators on the
      influence of topological structures to the collective dynamical behavior of
      complex networks. Recent findings on the ensemble averageability of the extreme
      eigenvalue have further authenticated its applicability to the study of network
      dynamics. However, the ensemble average of extreme eigenvalue has only been
      solved analytically up to the second order correction. Here, we determine the
      ensemble average of the extreme eigenvalue and characterize its deviation across
      the ensemble through the discrete form of random scale-free network. Remarkably,
      the analytical approximation derived from the discrete form shows significant
      improvement over previous results, which implies a more accurate prediction of
      the epidemic threshold. In addition, we show that bimodal networks, which are
      more robust against both random and targeted removal of nodes, are more
      vulnerable to the spreading of diseases.

PMID- 22463016
TI  - Impulsive synchronization of coupled dynamical networks with nonidentical Duffing
      oscillators and coupling delays.
AB  - This paper aims to investigate the synchronization problem of coupled dynamical
      networks with nonidentical Duffing-type oscillators without or with coupling
      delays. Different from cluster synchronization of nonidentical dynamical networks
      in the previous literature, this paper focuses on the problem of complete
      synchronization, which is more challenging than cluster synchronization. By
      applying an impulsive controller, some sufficient criteria are obtained for
      complete synchronization of the coupled dynamical networks of nonidentical
      oscillators. Furthermore, numerical simulations are given to verify the
      theoretical results.

PMID- 22463018
TI  - Reflection-mode submicron-resolution in vivo photoacoustic microscopy.
AB  - Submicron-resolution photoacoustic microscopy (PAM) currently exists only in
      transmission mode, due to the technical difficulties of combining high numerical
      aperture (NA) optical illumination with high NA acoustic detection. The lateral
      resolution of reflection-mode PAM has not reached <2 MUm in the visible light
      range. Here we develop the first reflection-mode submicron-resolution PAM system
      with a new compact design. By using a parabolic mirror to focus and reflect the
      photoacoustic waves, sufficient signals were collected for good sensitivity
      without distorting the optical focusing. By imaging nanospheres and a resolution
      test chart, the lateral resolution was measured to be ~ 0.5 MUm with an optical
      wavelength of 532 nm, an optical NA of 0.63. The axial resolution was measured at
      15 MUm. Here the axial resolution was measured by a different experiment with the
      lateral resolution measurement. But we didn't describe the details of axial
      resolution measurement due to space limit. The maximum penetration was measured
      at ~ 0.42 mm in optical-scattering soft tissue. As a comparison, both the
      submicron-resolution PAM and a 2.4 MUm-resolution PAM were used to image a mouse
      ear in vivo with the same optical wavelength and similar pulse energy.
      Capillaries were resolved better by the submicron-resolution PAM. Therefore, the
      submicron-resolution PAM is suitable for in vivo high-resolution imaging, or even
      subcellular imaging, of optical absorption.

PMID- 22463019
TI  - Endomicroscopy technologies and biomedical applications.

PMID- 22463020
TI  - In vivo near-infrared dual-axis confocal microendoscopy in the human lower
      gastrointestinal tract.
AB  - Near-infrared confocal microendoscopy is a promising technique for deep in vivo
      imaging of tissues and can generate high-resolution cross-sectional images at the
      micron-scale. We demonstrate the use of a dual-axis confocal (DAC) near-infrared
      fluorescence microendoscope with a 5.5-mm outer diameter for obtaining clinical
      images of human colorectal mucosa. High-speed two-dimensional en face scanning
      was achieved through a microelectromechanical systems (MEMS) scanner while a
      micromotor was used for adjusting the axial focus. In vivo images of human
      patients are collected at 5 frames/sec with a field of view of 362*212 MUm(2) and
      a maximum imaging depth of 140 MUm. During routine endoscopy, indocyanine green
      (ICG) was topically applied a nonspecific optical contrasting agent to regions of
      the human colon. The DAC microendoscope was then used to obtain microanatomic
      images of the mucosa by detecting near-infrared fluorescence from ICG. These
      results suggest that DAC microendoscopy may have utility for visualizing the
      anatomical and, perhaps, functional changes associated with colorectal pathology
      for the early detection of colorectal cancer.

PMID- 22463021
TI  - Targeted detection of murine colonic dysplasia in vivo with flexible
      multispectral scanning fiber endoscopy.
AB  - Gastrointestinal cancers are heterogeneous and can overexpress several protein
      targets that can be imaged simultaneously on endoscopy using multiple molecular
      probes. We aim to demonstrate a multispectral scanning fiber endoscope for wide
      field fluorescence detection of colonic dysplasia. Excitation at 440, 532, and
      635 nm is delivered into a single spiral scanning fiber, and fluorescence is
      collected by a ring of light-collecting optical fibers placed around the
      instrument periphery. Specific-binding peptides are selected with phage display
      technology using the CPC;Apc mouse model of spontaneous colonic dysplasia.
      Validation of peptide specificity is performed on flow cytometry and in vivo
      endoscopy. The peptides KCCFPAQ, AKPGYLS, and LTTHYKL are selected and labeled
      with 7-diethylaminocoumarin-3-carboxylic acid (DEAC), 5
      carboxytetramethylrhodamine (TAMRA), and CF633, respectively. Separate droplets
      of KCCFPAQ-DEAC, AKPGYLS-TAMRA, and LTTHYKL-CF633 are distinguished at
      concentrations of 100 and 1 MUM. Separate application of the fluorescent-labeled
      peptides demonstrate specific binding to colonic adenomas. The average
      target/background ratios are 1.71 +/- 0.19 and 1.67 +/- 0.12 for KCCFPAQ-DEAC and
      AKPGYLS-TAMRA, respectively. Administration of these two peptides together
      results in distinct binding patterns in the blue and green channels. Specific
      binding of two or more peptides can be distinguished in vivo using a novel
      multispectral endoscope to localize colonic dysplasia on real-time wide-field
      imaging.

PMID- 22463022
TI  - Foveated endoscopic lens.
AB  - We present a foveated miniature endoscopic lens implemented by amplifying the
      optical distortion of the lens. The resulting system provides a high-resolution
      region in the central field of view and low resolution in the outer fields, such
      that a standard imaging fiber bundle can provide both the high resolution needed
      to determine tissue health and the wide field of view needed to determine the
      location within the inspected organ. Our proof of concept device achieves 7 ~ 8
      MUm resolution in the fovea and an overall field of view of 4.6 mm. Example
      images and videos show the foveated lens' capabilities.

PMID- 22463023
TI  - Fast optically sectioned fluorescence HiLo endomicroscopy.
AB  - We describe a nonscanning, fiber bundle endomicroscope that performs optically
      sectioned fluorescence imaging with fast frame rates and real-time processing.
      Our sectioning technique is based on HiLo imaging, wherein two widefield images
      are acquired under uniform and structured illumination and numerically processed
      to reject out-of-focus background. This work is an improvement upon an earlier
      demonstration of widefield optical sectioning through a flexible fiber bundle.
      The improved device features lateral and axial resolutions of 2.6 and 17 MUm,
      respectively, a net frame rate of 9.5 Hz obtained by real-time image processing
      with a graphics processing unit (GPU) and significantly reduced motion artifacts
      obtained by the use of a double-shutter camera. We demonstrate the performance of
      our system with optically sectioned images and videos of a fluorescently labeled
      chorioallantoic membrane (CAM) in the developing G. gallus embryo. HiLo
      endomicroscopy is a candidate technique for low-cost, high-speed clinical optical
      biopsies.

PMID- 22463024
TI  - Singlet gradient index lens for deep in vivo multiphoton microscopy.
AB  - Micro-optical probes, including gradient index (GRIN) lenses and microprisms,
      have expanded the range of in vivo multiphoton microscopy to reach previously
      inaccessible deep brain structures such as deep cortical layers and the
      underlying hippocampus in mice. Yet imaging with GRIN lenses has been
      fundamentally limited by large amounts of spherical aberration and the need to
      construct compound lenses that limit the field-of-view. Here, we demonstrate the
      use of 0.5-mm-diameter, 1.7-mm-long GRIN lens singlets with 0.6 numerical
      aperture in conjunction with a cover glass and a conventional microscope
      objective correction collar to balance spherical aberrations. The resulting
      system achieves a lateral resolution of 618 nm and an axial resolution of 5.5
      MUm, compared to lateral and axial resolutions of ~ 1 MUm and ~ 15 MUm,
      respectively, for compound GRIN lenses of similar diameter. Furthermore, the GRIN
      lens singlets display fields-of-view in excess of 150 MUm, compared with a few
      tens of microns for compound GRIN lenses. The GRIN lens/cover glass combination
      presented here is easy to assemble and inexpensive enough for use as a disposable
      device, enabling ready adoption by the neuroscience community.

PMID- 22463025
TI  - Live animal myelin histomorphometry of the spinal cord with video-rate multimodal
      nonlinear microendoscopy.
AB  - In vivo imaging of cellular dynamics can be dramatically enabling to understand
      the pathophysiology of nervous system diseases. To fully exploit the power of
      this approach, the main challenges have been to minimize invasiveness and
      maximize the number of concurrent optical signals that can be combined to probe
      the interplay between multiple cellular processes. Label-free coherent anti
      Stokes Raman scattering (CARS) microscopy, for example, can be used to follow
      demyelination in neurodegenerative diseases or after trauma, but myelin imaging
      alone is not sufficient to understand the complex sequence of events that leads
      to the appearance of lesions in the white matter. A commercially available
      microendoscope is used here to achieve minimally invasive, video-rate multimodal
      nonlinear imaging of cellular processes in live mouse spinal cord. The system
      allows for simultaneous CARS imaging of myelin sheaths and two-photon excitation
      fluorescence microendoscopy of microglial cells and axons. Morphometric data
      extraction at high spatial resolution is also described, with a technique for
      reducing motion-related imaging artifacts. Despite its small diameter, the
      microendoscope enables high speed multimodal imaging over wide areas of tissue,
      yet at resolution sufficient to quantify subtle differences in myelin thickness
      and microglial motility.

PMID- 22463026
TI  - Increased illumination uniformity and reduced photodamage offered by the
      Lissajous scanning in fiber-optic two-photon endomicroscopy.
AB  - We compare the illumination uniformity and the associated effects of the spiral
      and Lissajous scanning patterns that are commonly used in an endomicroscope.
      Theoretical analyses and numerical simulations were first performed to
      quantitatively investigate the area illumination density in the spiral scanning
      pattern. The results revealed the potential problem of manifest photodamage due
      to the very high illumination density in the center of the spiral scan. Similar
      analyses of the Lissajous scanning pattern, which can be conveniently implemented
      on the same endomicroscope with no hardware modifications, showed a more uniform
      illumination density with about an 80-fold reduction in the peak illumination
      density. To underscore the benefit offered by the improved illumination
      uniformity, we conducted in vitro two-photon fluorescence imaging of cultured
      cells stained with a LIVE/DEAD viability assay using our home-built, fiber-optic,
      two-channel endomicroscopy system. Both the spiral and the Lissajous scans were
      implemented. Our experimental results showed that cells near the spiral scan
      center experienced obvious photodamage, whereas cells remained alive over the
      entire region under the Lissajous beam scanning, confirming the predicted
      advantage offered by the Lissajous scan over this spiral scan in an
      endomicroscopy setting.

PMID- 22463027
TI  - Normal and system lupus erythematosus red blood cell interactions studied by
      double trap optical tweezers: direct measurements of aggregation forces.
AB  - Direct measurements of aggregation forces in piconewton range between two red
      blood cells in pair rouleau are performed under physiological conditions using
      double trap optical tweezers. Aggregation and disaggregation properties of
      healthy and pathologic (system lupus erythematosis) blood samples are analyzed.
      Strong difference in aggregation speed and behavior is revealed using the offered
      method which is proposed to be a promising tool for SLE monitoring at single cell
      level.

PMID- 22463028
TI  - On the sensitivity of thermophotonic lock-in imaging and polarized Raman
      spectroscopy to early dental caries diagnosis.
AB  - Dental caries is the leading cause of tooth loss, which can promptly be prevented
      if detected in early stages of progression. Unfortunately, conventional
      diagnostic modalities currently used in dentistry lack the sensitivity to detect
      early caries. The authors' intention is to compare the ability of polarized Raman
      spectroscopy and thermophotonic imaging to make early caries diagnosis. Extracted
      human teeth with no visible stain or defects were artificially demineralized in
      accordance to a well-known protocol in dentistry for simulated early caries
      development at several demineralization stages. Samples were then inspected using
      polarized Raman spectroscopy and thermophotonic imaging. The sensitivities of
      these two diagnostic modalities are compared, and the results are verified using
      transverse micro-radiography. It was found that compared to polarized Raman
      spectroscopy, thermophotonic imaging exhibits superior sensitivity to very early
      stages of demineralization.

PMID- 22463029
TI  - Two-photon excited fluorescence enhancement with broadband versus tunable
      femtosecond laser pulse excitation.
AB  - The inverse relationship between two-photon excited fluorescence (TPEF) and laser
      pulse duration suggests that two-photon microscopy (TPM) performance may be
      improved by decreasing pulse duration. However, for ultrashort pulses of sub-10
      femtosecond (fs) in duration, its spectrum contains the effective gain bandwidth
      of Ti:Sapphire and its central wavelength is no longer tunable. An experimental
      study was performed to explore this apparent tradeoff between untuned sub-10 fs
      transform-limited pulse (TLP) and tunable 140 fs pulse for TPEF. Enhancement
      factors of 1.6, 6.7, and 5.2 are measured for Indo-1, FITC, and TRITC excited by
      sub-10 fs TLP compared with 140 fs pulse tuned to the two-photon excitation (TPE)
      maxima at 730 nm, 800 nm, and 840 nm, respectively. Both degenerate (v(1) = v(2))
      and nondegenerate (v(1) ? v(2)) mixing of sub-10 fs TLP spectral components
      result in its broad second-harmonic (SH) power spectrum and high spectral
      density, which can effectively compensate for the lack of central wavelength
      tuning and lead to large overlap with dye TPE spectra for TPEF enhancements.
      These pulse properties were also exploited for demonstrating its potential
      applications in multicolor imaging with TPM.

PMID- 22463030
TI  - Specifying peripheral aberrations in visual science.
AB  - PURPOSE: Investigations of foveal aberrations assume circular pupils. However,
      the pupil becomes increasingly elliptical with increase in visual field
      eccentricity. We address this and other issues concerning peripheral aberration
      specification. METHODS: One approach uses an elliptical pupil similar to the
      actual pupil shape, stretched along its minor axis to become a circle so that
      Zernike circular aberration polynomials may be used. Another approach uses a
      circular pupil whose diameter matches either the larger or smaller dimension of
      the elliptical pupil. Pictorial presentation of aberrations, influence of
      wavelength on aberrations, sign differences between aberrations for fellow eyes,
      and referencing position to either the visual field or the retina are considered.
      RESULTS: Examples show differences between the two approaches. Each has its
      advantages and disadvantages, but there are ways to compensate for most
      disadvantages. Two representations of data are pupil aberration maps at each
      position in the visual field and maps showing the variation in individual
      aberration coefficients across the field. CONCLUSIONS: Based on simplicity of
      use, adequacy of approximation, possible departures of off-axis pupils from
      ellipticity, and ease of understanding by clinicians, the circular pupil approach
      is preferable to the stretched elliptical approach for studies involving field
      angles up to 30 deg.

PMID- 22463031
TI  - Effects of viscosity on sperm motility studied with optical tweezers.
AB  - The purpose of this study is to analyze human sperm motility and energetics in
      media with different viscosities. Multiple experiments were performed to collect
      motility parameters using customized computer tracking software that measures the
      curvilinear velocity (VCL) and the minimum laser power (Pesc) necessary to hold
      an individual sperm in an optical trap. The Pesc was measured by using a 1064 nm
      Nd:YVO(4) continuous wave laser that optically traps motile sperm at a power of
      450 mW in the focused trap spot. The VCL was measured frame by frame before
      trapping. In order to study sperm energetics under different viscous conditions
      sperm were labeled with the fluorescent dye DiOC(6)(3) to measure membrane
      potentials of mitochondria in the sperm midpiece. Fluorescence intensity was
      measured before and during trapping. The results demonstrate a decrease in VCL
      but an increase in Pesc with increasing viscosity. Fluorescent intensity is the
      same regardless of the viscosity level indicating no change in sperm energetics.
      The results suggest that, under the conditions tested, viscosity physically
      affects the mechanical properties of sperm motility rather than the chemical
      pathways associated with energetics.

PMID- 22463032
TI  - Extraction of effective parameters of anisotropic optical materials using a
      decoupled analytical method.
AB  - A decoupled analytical technique based on the Mueller matrix method and the
      Stokes parameters is proposed for extracting effective parameters of anisotropic
      optical materials in linear birefringence (LB), linear dichroism (LD), circular
      birefrinegence (CB), and circular dichroism (CD) properties. This technique is
      essential in determining the optical properties of opto-electric or biomedical
      materials for the development of advanced inspection and/or diagnostic
      applications. The error and resolution analysis of the proposed approach is
      demonstrated by extracting the effective parameters given an assumption of errors
      ranging +/- 0.005 in the values of the output Stokes parameters. The results
      confirm the ability of the proposed method to yield full-range measurements of
      all the optical parameters. The decoupled nature of the analytical model yields
      several important advantages, including an improved accuracy and the ability to
      extract the parameters of optical samples with only LB, CB, LD, or CD property
      without using compensation technique or pretreatment. Moreover, by decoupling the
      extraction process, the "multiple solutions" problem inherent in previous models
      presented by the current group is avoided.

PMID- 22463033
TI  - Optimization of the open-loop liquid crystal adaptive optics retinal imaging
      system.
AB  - An open-loop adaptive optics (AO) system for retinal imaging was constructed
      using a liquid crystal spatial light modulator (LC-SLM) as the wavefront
      compensator. Due to the dispersion of the LC-SLM, there was only one illumination
      source for both aberration detection and retinal imaging in this system. To
      increase the field of view (FOV) for retinal imaging, a modified mechanical
      shutter was integrated into the illumination channel to control the size of the
      illumination spot on the fundus. The AO loop was operated in a pulsing mode, and
      the fundus was illuminated twice by two laser impulses in a single AO correction
      loop. As a result, the FOV for retinal imaging was increased to 1.7-deg without
      compromising the aberration detection accuracy. The correction precision of the
      open-loop AO system was evaluated in a closed-loop configuration; the residual
      error is approximately 0.0909lambda (root-mean-square, RMS), and the Strehl ratio
      ranges to 0.7217. Two subjects with differing rates of myopia (-3D and -5D) were
      tested. High-resolution images of capillaries and photoreceptors were obtained.

PMID- 22463034
TI  - Effect of tissue optics on wavelength optimization for quantum dot-based surface
      and subsurface fluorescence imaging.
AB  - Optimization is an important but relatively unexplored aspect of contrast
      enhanced fluorescence imaging, since minimizing contrast agent usage reduces the
      associated cost and potential toxicity. In a previous study, the authors
      developed a quantitative experimental approach to optimize quantum dot (QD)-based
      imaging using homogenized liver as a model tissue. In this follow-up study, the
      authors further extend and validate the approach using eight different tissues
      and five QDs emission wavelengths, and introduce quantitative imaging performance
      metrics, namely the threshold QD concentration and wavelength optimization gain.
      These metrics allow quantification of the improvements through spectral
      optimization in terms of reduced QD dose and identify the conditions that make
      the optimization process worthwhile. The authors show that, for most tissues, the
      most important parameter to optimize is the emission wavelength, yielding
      improvements of up to four orders of magnitude, followed by the excitation
      wavelength (up to 20-fold improvement) and the excitation filter bandwidth (up to
      50% improvement). The authors also observe, by means of the optimization gain
      metric, that tissues exhibiting both high autofluorescence and strong
      pigmentation are generally better candidates for excitation wavelength
      optimization. This work contributes to the development of robust and quantitative
      dosimetry for QD-based fluorescence imaging near to the tissue surface.

PMID- 22463035
TI  - Three-dimensional differential interference contrast microscopy using synthetic
      aperture imaging.
AB  - We implement differential interference contrast (DIC) microscopy using high-speed
      synthetic aperture imaging that expands the passband of coherent imaging by a
      factor of 2.2. For an aperture synthesized coherent image, we apply for the
      numerical post-processing and obtain a high-contrast DIC image for arbitrary
      shearing direction and bias retardation. In addition, we obtain images at
      different depths without a scanning objective lens by numerically propagating the
      acquired coherent images. Our method achieves high-resolution and high-contrast 3
      D DIC imaging of live biological cells. The proposed method will be useful for
      monitoring 3-D dynamics of intracellular particles.

PMID- 22463036
TI  - Preclinical study of using multiphoton microscopy to diagnose liver cancer and
      differentiate benign and malignant liver lesions.
AB  - Recently, the miniaturized multiphoton microscopy (MPM) and multiphoton probe
      allow the clinical use of multiphoton endoscopy for diagnosing cancer via
      "optical biopsy". The purpose of this study was to establish MPM optical
      diagnostic features for liver cancer and evaluate the sensitivity, specificity,
      and accuracy of MPM optical diagnosis. Firstly, we performed a pilot study to
      establish the MPM diagnostic features by investigating 60 surgical specimens, and
      found that high-resolution MPM images clearly demonstrated apparent differences
      between benign and malignant liver lesions in terms of their tissue architecture
      and cell morphology. Cancer cells, characterized by irregular size and shape,
      enlarged nuclei, and increased nuclear-cytoplasmic ratio, were identified by MPM
      images, which were comparable to hematoxylin-eosin staining images. Secondly, we
      performed a blinded study to evaluate the sensitivity, specificity, and accuracy
      of MPM optical diagnosis by investigating another 164 specimens, and found that
      the sensitivity, specificity, and accuracy of MPM diagnosis was 96.32%, 96.43%,
      and 96.34%, respectively. In conclusion, it is feasible to use MPM to diagnose
      liver cancer and differentiate benign and malignant liver lesions. This
      preclinical study provides the groundwork for further using multiphoton endoscopy
      to perform real-time noninvasive "optical biopsy" for liver lesions in the near
      future.

PMID- 22463037
TI  - Automatic three-dimensional registration of intravascular optical coherence
      tomography images.
AB  - Intravascular optical coherence tomography (IV-OCT) is a catheter-based high
      resolution imaging technique able to visualize the inner wall of the coronary
      arteries and implanted devices in vivo with an axial resolution below 20 MUm. IV
      OCT is being used in several clinical trials aiming to quantify the vessel
      response to stent implantation over time. However, stent analysis is currently
      performed manually and corresponding images taken at different time points are
      matched through a very labor-intensive and subjective procedure. We present an
      automated method for the spatial registration of IV-OCT datasets. Stent struts
      are segmented through consecutive images and three-dimensional models of the
      stents are created for both datasets to be registered. The two models are
      initially roughly registered through an automatic initialization procedure and an
      iterative closest point algorithm is subsequently applied for a more precise
      registration. To correct for nonuniform rotational distortions (NURDs) and other
      potential acquisition artifacts, the registration is consecutively refined on a
      local level. The algorithm was first validated by using an in vitro experimental
      setup based on a polyvinyl-alcohol gel tubular phantom. Subsequently, an in vivo
      validation was obtained by exploiting stable vessel landmarks. The mean
      registration error in vitro was quantified to be 0.14 mm in the longitudinal axis
      and 7.3-deg mean rotation error. In vivo validation resulted in 0.23 mm in the
      longitudinal axis and 10.1-deg rotation error. These results indicate that the
      proposed methodology can be used for automatic registration of in vivo IV-OCT
      datasets. Such a tool will be indispensable for larger studies on vessel healing
      pathophysiology and reaction to stent implantation. As such, it will be valuable
      in testing the performance of new generations of intracoronary devices and new
      therapeutic drugs.

PMID- 22463038
TI  - Use of near-infrared luminescent gold nanoclusters for detection of macrophages.
AB  - We determined the effect of aggregation and coating thickness of gold on the
      luminescence of nanoparticles engulfed by macrophages and in gelatin phantoms.
      Thin gold-coated iron oxide nanoclusters (nanoroses) have been developed to
      target macrophages to provide contrast enhancement for near-infrared optical
      imaging applications. We compare the brightness of nanoroses luminescent
      emissions in response to 635 nm laser excitation to other nanoparticles including
      nanoshells, nanorods, and Cy5 conjugated iron oxide nanoparticles. Luminescent
      properties of all these nanoparticles were investigated in monomeric and
      aggregated form in gelatin phantoms and primary macrophage cell cultures using
      confocal microscopy. Aggregation of the gold nanoparticles increased luminescence
      emission and correlated with increased surface mass of gold per nanoparticle
      (nanoshells 37 +/- 14.30 * 10(-3) brightness with 1.23 * 10(-4) wt of gold
      (g)/nanoparticle versus original nanorose 1.45 +/- 0.37 * 10(-3) with 2.10 * 10(
      16) wt of gold/nanoparticle, p<0.05). Nanoshells showed greater luminescent
      intensity than original nanoroses or Cy5 conjugated iron oxide nanoparticles when
      compared as nanoparticles per macrophage (38 +/- 10 versus 11 +/- 2.8 versus 17
      +/- 6.5, p<0.05, respectively, ANOVA), but showed relatively poor macrophage
      uptake (1025 +/- 128 versus 7549 +/- 236 versus 96,000 nanoparticles/cell,
      p<0.05, student t-test nanoshells versus nanoroses). Enhancement of gold
      fluorescent emissions by nanoparticles can be achieved by reducing the thickness
      of the gold coating, by clustering the gold on the surface of the nanoparticles
      (nanoshells), and by clustering the gold nanoparticles themselves.

PMID- 22463039
TI  - Characterization of collagen fibers by means of texture analysis of second
      harmonic generation images using orientation-dependent gray level co-occurrence
      matrix method.
AB  - Collagen is the most prominent protein in the human body, making up 30% of the
      total protein content. Quantitative studies have shown structural differences
      between collagen fibers of the normal and diseased tissues, due to the remodeling
      of the extracellular matrix during the pathological process. The dominant
      orientation, which is an important characteristic of collagen fibers, has not
      been taken into consideration for quantitative collagen analysis. Based on the
      conventional gray level co-occurrence matrix (GLCM) method, the authors proposed
      the orientation-dependent GLCM (OD-GLCM) method by estimating the dominant
      orientation of collagen fibers. The authors validated the utility of the OD-GLCM
      method on second harmonic generation (SHG) microscopic images of tendons from
      rats with different ages. Compared with conventional GLCM method, the authors'
      method has not only improved the discrimination between different tissues but
      also provided additional texture information of the orderliness of collagen
      fibers and the fiber size. The OD-GLCM method was further applied to the
      differentiation of the preliminary SHG images of normal and cancerous human
      pancreatic tissues. The combination of SHG microscopy and the OD-GLCM method
      might be helpful for the evaluation of diseases marked with abnormal collagen
      morphology.

PMID- 22463040
TI  - Angiography with a multifunctional line scanning ophthalmoscope.
AB  - A multifunctional line scanning ophthalmoscope (mLSO) was designed, constructed,
      and tested on human subjects. The mLSO could sequentially acquire wide-field,
      confocal, near-infrared reflectance, fluorescein angiography (FA), and
      indocyanine green angiography (ICGA) retinal images. The system also included a
      retinal tracker (RT) and a photodynamic therapy laser treatment port. The mLSO
      was tested in a pilot clinical study on human subjects with and without retinal
      disease. The instrument exhibited robust retinal tracking and high-contrast line
      scanning imaging. The FA and ICGA angiograms showed a similar appearance of hyper
      and hypo-pigmented disease features and a nearly equivalent resolution of fine
      capillaries compared to a commercial flood-illumination fundus imager. An mLSO
      based platform will enable researchers and clinicians to image human and animal
      eyes with a variety of modalities and deliver therapeutic beams from a single
      automated interface. This approach has the potential to improve patient comfort
      and reduce imaging session times, allowing clinicians to better diagnose, plan,
      and conduct patient procedures with improved outcomes.

PMID- 22463041
TI  - In vivo multiphoton imaging of human skin: assessment of topical corticosteroid
      induced epidermis atrophy and depigmentation.
AB  - Multiphoton microscopy has emerged in the past decade as a promising tool for
      noninvasive skin imaging. Our aim was to evaluate the potential of multiphoton
      microscopy to detect topical corticosteroids side effects within the epidermis
      and to provide new insights into their dynamics. Healthy volunteers were
      topically treated with clobetasol propionate on a small region of their forearms
      under overnight occlusion for three weeks. The treated region of each patient was
      investigated at D0, D7, D15, D22 (end of the treatment), and D60. Our study shows
      that multiphoton microscopy allows for the detection of corticoid-induced
      epidermis modifications: thinning of stratum corneum compactum and epidermis,
      decrease of keratinocytes size, and changes in their morphology from D7 to D22.
      We also show that multiphoton microscopy enables in vivo three-dimensional (3-D)
      quantitative assessment of melanin content. We observe that melanin density
      decreases during treatment and almost completely disappears at D22. Moreover,
      these alterations are reversible as they are no longer present at D60. Our study
      demonstrates that multiphoton microscopy is a convenient and powerful tool for
      noninvasive 3-D dynamical studies of skin integrity and pigmentation.

PMID- 22463042
TI  - Hyperspectral imaging for early detection of oxygenation and perfusion changes in
      irradiated skin.
AB  - Studies examining acute oxygenation and perfusion changes in irradiated skin are
      limited. Hyperspectral imaging (HSI), a method of wide-field, diffuse reflectance
      spectroscopy, provides noninvasive, quantified measurements of cutaneous
      oxygenation and perfusion. This study examines whether HSI can assess acute
      changes in oxygenation and perfusion following irradiation. Skin on both flanks
      of nude mice (n=20) was exposed to 50 Gy of beta radiation from a strontium-90
      source. Hyperspectral images were obtained before irradiation and on selected
      days for three weeks. Skin reaction assessment was performed concurrently with
      HSI. Desquamative injury formed in all irradiated areas. Skin reactions were
      first seen on day 7, with peak formation on day 14, and resolution beginning by
      day 21. HSI demonstrated increased tissue oxygenation on day 1 before cutaneous
      changes were observed (p<0.001). Further increases over baseline were seen on day
      14, but returned to baseline levels by day 21. For perfusion, similar increases
      were seen on days 1 and 14. Unlike tissue oxygenation, perfusion was decreased
      below baseline on day 21 (p<0.002). HSI allows for complete visualization and
      quantification of tissue oxygenation and perfusion changes in irradiated skin,
      and may also allow prediction of acute skin reactions based on early changes seen
      after irradiation.

PMID- 22463043
TI  - Differential phase-contrast, swept-source optical coherence tomography at 1060 nm
      for in vivo human retinal and choroidal vasculature visualization.
AB  - Human retinal and choroidal vasculature was visualized by a differential phase
      contrast (DPC) method using high-speed, swept-source optical coherence tomography
      (SS-OCT) at 1060 nm. The vasculature was recognized as regions of motion by
      creating differential phase-variance (DPV) tomograms: multiple B-scans of
      individual slices through the retina were collected and the variance of the phase
      differences was calculated. DPV captured the small vessels and the meshwork of
      capillaries associated with the inner retina in en-face images over 4 mm(2). The
      swept-source laser at 1060 nm offered the needed phase sensitivity to perform DPV
      and generated en-face images that capture motion in the inner choroidal layer
      exceeding the capabilities of previous spectrometer-based instruments. In
      comparison with the power Doppler phase-shift method, DPV provided better
      visualization of the foveal avascular zone in en-face images.

PMID- 22463044
TI  - Identifying brain neoplasms using dye-enhanced multimodal confocal imaging.
AB  - Brain tumors cause significant morbidity and mortality even when benign.
      Completeness of resection of brain tumors improves quality of life and survival;
      however, that is often difficult to accomplish. The goal of this study was to
      evaluate the feasibility of using multimodal confocal imaging for intraoperative
      detection of brain neoplasms. We have imaged different types of benign and
      malignant, primary and metastatic brain tumors. We correlated optical images with
      histopathology and evaluated the possibility of interpreting confocal images in a
      manner similar to pathology. Surgical specimens were briefly stained in 0.05
      mg/ml aqueous solution of methylene blue (MB) and imaged using a multimodal
      confocal microscope. Reflectance and fluorescence signals of MB were excited at
      642 nm. Fluorescence emission of MB was registered between 670 and 710 nm. After
      imaging, tissues were processed for hematoxylin and eosin (H&E) histopathology.
      The results of comparison demonstrate good correlation between fluorescence
      images and histopathology. Reflectance images provide information about
      morphology and vascularity of the specimens, complementary to that provided by
      fluorescence images. Multimodal confocal imaging has the potential to aid in the
      intraoperative detection of microscopic deposits of brain neoplasms. The
      application of this technique may improve completeness of resection and increase
      patient survival.

PMID- 22463046
TI  - Application of a maximum likelihood algorithm to ultrasound modulated optical
      tomography.
AB  - In pulsed ultrasound modulated optical tomography (USMOT), an ultrasound (US)
      pulse performs as a scanning probe within the sample as it propagates, modulating
      the scattered light spatially distributed along its propagation axis. Detecting
      and processing the modulated signal can provide a 1-dimensional image along the
      US axis. A simple model is developed wherein the detected signal is modelled as a
      convolution of the US pulse and the properties (ultrasonic/optical) of the medium
      along the US axis. Based upon this model, a maximum likelihood (ML) method for
      image reconstruction is established. For the first time to our knowledge, the ML
      technique for an USMOT signal is investigated both theoretically and
      experimentally. The ML method inverts the data to retrieve the spatially varying
      properties of the sample along the US axis, and a signal proportional to the
      optical properties can be acquired. Simulated results show that the ML method can
      serve as a useful reconstruction tool for a pulsed USMOT signal even when the
      signal-to-noise ratio (SNR) is close to unity. Experimental data using 5 cm thick
      tissue phantoms (scattering coefficient MU(s) = 6.5 cm(-1), anisotropy factor
      g=0.93) demonstrate that the axial resolution is 160 MUm and the lateral
      resolution is 600 MUm using a 10 MHz transducer.

PMID- 22463045
TI  - Methodological considerations for global analysis of cellular FLIM/FRET
      measurements.
AB  - Global algorithms can improve the analysis of fluorescence energy transfer (FRET)
      measurement based on fluorescence lifetime microscopy. However, global analysis
      of FRET data is also susceptible to experimental artifacts. This work examines
      several common artifacts and suggests remedial experimental protocols.
      Specifically, we examined the accuracy of different methods for instrument
      response extraction and propose an adaptive method based on the mean lifetime of
      fluorescent proteins. We further examined the effects of image segmentation and a
      priori constraints on the accuracy of lifetime extraction. Methods to test the
      applicability of global analysis on cellular data are proposed and demonstrated.
      The accuracy of global fitting degrades with lower photon count. By
      systematically tracking the effect of the minimum photon count on lifetime and
      FRET prefactors when carrying out global analysis, we demonstrate a correction
      procedure to recover the correct FRET parameters, allowing us to obtain protein
      interaction information even in dim cellular regions with photon counts as low as
      100 per decay curve.

PMID- 22463047
TI  - Quantitative 3-D colocalization analysis as a tool to study the intracellular
      trafficking and dissociation of pDNA-chitosan polyplexes.
AB  - Multichannel microscopy is frequently used to study intermolecular interactions
      and spatial relationships between biomolecules and organelles or vesicles in
      cells. Based on multichannel images, quantitative colocalization analysis can
      provide valuable information about cellular internalization, vesicular transport,
      and the intracellular kinetics and location of biomolecules. However, such
      analyses should be performed carefully, because quantitative colocalization
      parameters have different interpretations and can be highly affected by image
      quality. We use quantitative three-dimensional colocalization analysis of
      deconvolved and chromatic-registered confocal images to study the dissociation of
      double-labeled pDNA-chitosan polyplexes in HeLa cells and their colocalization
      with early endosomes. Two chitosans that form polyplexes with highly different
      transfection efficacies are compared. Pearson's correlation coefficient, Manders'
      colocalization coefficients, and the intensity correlation quotient are estimated
      to determine the intracellular localization of polyplexes, free pDNA, and free
      chitosans. Differences are observed in the amount of uptake, and in the
      intracellular pathways and rates of dissociation for the two chitosans. The
      results support previous findings that polyplexes formed by self-branched,
      glycosylated chitosan oligomers are more favorable for cellular uptake and
      intracellular trafficking to the nucleus compared with polyplexes formed by
      linear chitosans.

PMID- 22463048
TI  - Discrimination of periodontal diseases using diffuse reflectance spectral
      intensity ratios.
AB  - This clinical study was to demonstrate the applicability of diffuse reflectance
      (DR) intensity ratio R620/R575 in the quantification and discrimination of
      periodontitis and gingivitis from healthy gingiva. DR spectral measurements were
      carried out with white-light illumination from 70 healthy sites in 30 healthy
      volunteers, and 63 gingivitis- and 58 periodontitis-infected sites in 60
      patients. Clinical parameters such as probing pocket depth, clinical attachment
      level, and gingival index were recorded in patient population. Diagnostic
      accuracies for discrimination of gingivitis and periodontitis from healthy
      gingiva were determined by comparison of spectral signatures with clinical
      parameters. Divergence of average DR spectral intensity ratio between control and
      test groups was studied using analysis of variance. The mean DR spectrum on
      normalization at 620 nm showed marked differences between healthy tissue,
      gingivitis, and periodontitis. Hemoglobin concentration and apparent SO(2)
      (oxygen saturation) were also calculated for healthy, gingivitis, and
      periodontitis sites. DR spectral intensities at 545 and 575 nm showed a
      decreasing trend with progression of disease. Among the various DR intensity
      ratios studied, the R620/R575 ratio provided a sensitivity of 90% and specificity
      of 94% for discrimination of healthy tissues from gingivitis and a sensitivity of
      91% and specificity of 100% for discrimination of gingivitis from periodontitis.

PMID- 22463049
TI  - Porcine cortical bone ablation by ultrashort pulsed laser irradiation.
AB  - Ultrashort pulsed lasers in bone ablation show promise for many orthopedic
      applications. To minimize collateral tissue damage and control the ablation
      process, the ablation threshold fluence must be well characterized. Using an
      amplified femtosecond laser (170 fs, 800 nm, 1 kHz), the ablation threshold on
      unaltered porcine cortical bone was measured using the D(2) method at multiple
      incident pulse numbers ranging from 25 to 1000 pulses per spot. The lowered
      threshold at greater pulse numbers indicated an incubation effect. Using a power
      law model, the incubation coefficient of unaltered porcine cortical bone was
      found to be 0.89 +/- 0.03. Through extrapolation, the single-pulse ablation
      threshold was found to be 3.29 +/- 0.14 J/cm(2).

PMID- 22463050
TI  - Enhanced thulium fiber laser lithotripsy using micro-pulse train modulation.
AB  - The thulium fiber laser (TFL) is currently being studied as an alternative to the
      conventional holmium:YAG (Ho:YAG) laser for lithotripsy. The diode-pumped TFL may
      be electronically modulated to operate with variable parameters (e.g., pulse
      rate, pulse duration, and duty cycle) for studying the influence of pulse train
      mode on stone ablation rates. The TFL under study was operated at 1908 nm, 35-mJ
      pulse energy, and 500-MUs pulse duration, in a train of 5 micro-pulses, with
      macro-pulse rates of 10 Hz, compared with conventional TFL operation at 10 to 50
      Hz. TFL energy was delivered through 100-MUm-core fibers in contact with human
      uric acid (UA) and calcium oxalate monohydrate (COM) stones. Mass removal rates,
      optical coherence tomography, and light microscopy were used to analyze the
      ablation craters. Stone retropulsion and fiber tip degradation studies also were
      conducted for these laser parameters. TFL operation in micro-pulse train (MPT)
      mode resulted in a factor of two increase in the ablation rate of 414 +/- 94
      MUg/s and 122 +/- 24 MUg/s for the UA and COM stones, respectively, compared to
      182 +/- 69 MUg/s and 60 +/- 14 MUg/s with standard pulse trains delivered at 50
      Hz (P<0.05). Stone retropulsion remained minimal (<2 mm after 1200 pulses) for
      both pulse modes. Fiber burnback was significant for both pulse modes and was
      higher for COM stones than UA stones. TFL operation in MPT mode results in
      increased stone ablation rates which, with further optimization, may approach
      levels comparable to Ho:YAG laser lithotripsy in the clinic.

PMID- 22463052
TI  - Comparison of Tetrahymena pyriformis toxicity based on hydrophobicity, polarity,
      ionization and reactivity of class-based compounds.
AB  - A toxicity data set containing the toxicities of 970 hydrophobic, polar and
      ionizable, nitro substituted and alpha,beta-unsaturated compounds to Tetrahymena
      pyriformis was classified into different groups based on the structure and
      substituted functional groups. Polar, ionizable and reactive compounds exhibit
      greater toxicity as compared with the non-polar hydrophobic compounds. Step-by
      step analysis was carried out between the toxicity and descriptors representing
      hydrophobicity, polarity/polarizability, ionization and reactivity of compounds.
      Significant relationships were developed between the toxicity and these
      descriptors for the compounds. The models developed are simple, interpretable and
      transparent, using a small number of descriptors that may reflect the
      interactions of chemicals with the biological macromolecules at the target sites.
      Hydrophobic parameter log P reflects bio-uptake process compounds.
      Polarity/polarizability descriptor S reflects the interaction of hydrophilic
      residues of polar chemicals with biological macromolecules. The fractions of
      ionized (F (i)) and neutral (F (0)) forms calculated from pK (a) reflect the
      interactions of ionizable compounds with the macromolecules and effect of
      ionization of ionizable compounds on the bio-uptake process, respectively. A
      successful single model was developed by using the descriptors log P, S, F (i)
      and log F (0) for non-polar, polar and ionizable compounds.

PMID- 22463053
TI  - Bactericidal antibody response against P6, protein D, and OMP26 of nontypeable
      Haemophilus influenzae after acute otitis media in otitis-prone children.
AB  - The bactericidal antibody response to three nontypeable Haemophilus influenzae
      (NTHi) outer membrane proteins (D, P6, and OMP26) was studied in 24 otitis-prone
      children (aged 7-28 months) after an acute otitis media (AOM) caused by NTHi. The
      study was carried out to understand the contribution of antigen-specific
      bactericidal antibody responses in the class of children who are most vulnerable
      to recurrent otitis media infections. Levels of protein D (P = 0.005) and P6 (P =
      0.026) but not OMP26 antibodies were higher in bactericidal sera compared with
      nonbactericidal sera. For five (24%) and 16 (76%) of 21 bactericidal sera tested,
      removal of anti-protein D and P6 antibody, respectively, resulted in a two- to
      fourfold drop in bactericidal antibody. Antibodies to OMP26 did not make any
      contribution to the overall bactericidal activity in any serum samples. Eleven of
      21 sera (52%) had bactericidal activity against a heterologous NTHi (86-028 NP)
      strain but the titers were significantly lower (P < 0.05) as compared to the
      homologous strains. Future studies of protein D, P6, OMP26, and other potential
      NTHi vaccine antigens should include studies of bactericidal antibody in children
      who are otitis prone as a possible correlate of protection.

PMID- 22463054
TI  - Physical activity and circulating endothelial progenitor cells: an intervention
      study.
AB  - BACKGROUND: To assess the effect of a personalized physical activity programme on
      weight and circulating (CPC) and endothelial progenitor cells (EPC) in overweight
      and obese subjects. MATERIALS AND METHODS: Anthropometric measurements with body
      composition, cardiopulmonary test, maximal stress exercise test with maximal
      oxygen uptake (VO(2max) ) and a series of biochemical analyses were taken before
      (T0) and after 3 months of physical activity (T1) in a total of 80 overweight and
      obese subjects. CPC and EPC were determined using flow cytometry and were defined
      as CD34+, CD133+ and CD34+/CD133+ for CPC and CD34+KDR+, CD133+KDR+ and
      CD34+CD133+KDR+ for EPC. RESULTS: At the end of the programme, we divided the
      population into two groups, compliant individuals (group A, n = 47) and
      noncompliant individuals (group B, n = 33). Group A reported significant
      reductions of weight by 3.1% (P < 0.0001) and fat mass by 4.4% (P < 0.0001),
      while group B showed a percentage of increase in fat mass by 1.5% at T1. In group
      A, a trend of increase at T1 for circulating levels of CPC and EPC was observed,
      reaching the statistical significance for all the three types of EPC. On the
      contrary, group B showed no significant increase in CPC and EPC. Furthermore, a
      significant correlation between decrease in fat mass and increase in CD133+/KDR+
      EPC was reported in group A (r = 0.50; P = 0.04). CONCLUSION: Three months of
      physical activity significantly improved anthropometric measurements. A
      beneficial effect of increased number of EPC in compliant individuals, in
      relation to weight loss, was observed.

PMID- 22463055
TI  - Choice of antipsychotic treatment by European psychiatry trainees: are decisions
      based on evidence?
AB  - BACKGROUND: Little is known about the factors influencing treatment choice in
      psychosis, the majority of this work being conducted with specialists
      (consultant) in psychiatry. We sought to examine trainees' choices of treatment
      for psychosis if they had to prescribe it for themselves, their patients, and
      factors influencing decision-making. METHODS: Cross-sectional, semi-structured
      questionnaire-based study. RESULTS: Of the 726 respondents (response rate = 66%),
      the majority chose second-generation antipsychotics (SGAs) if they had to
      prescribe it for themselves (n = 530, 93%) or for their patients (n = 546, 94%).
      The main factor influencing choice was perceived efficacy, 84.8% (n = 475) of
      trainees stating this was the most important factor for the patient, and 77.8% (n
      = 404) stating this was the most important factor for their own treatment.
      Trainees with knowledge of trials questioning use of SGAs (CATIE, CUtLASS, TEOSS)
      were more likely to choose second-generation antipsychotics than those without
      knowledge of these trials (chi2 = 3.943; p = 0.047; O.R. = 2.11; 95% C.I. = 1.0
      4.48). Regarding psychotherapy, cognitive behavioural therapy (CBT) was the most
      popular choice for self (33.1%; n = 240) and patient (30.9%; n = 224). Trainees
      were significantly more likely to prefer some form of psychotherapy for
      themselves rather than patients (chi2 = 9.98; p < 0,002; O.R. = 1.54; 95% CIs =
      1.18-2.0). CONCLUSIONS: Trainees are more likely to choose second-generation
      antipsychotic medication for patients and themselves. Despite being aware of
      evidence that suggests otherwise, they predominantly base these choices on
      perceived efficacy.

PMID- 22463056
TI  - Structural homology in the Solanaceae: analysis of genomic regions in support of
      synteny studies in tomato, potato and pepper.
AB  - We have analysed the structural homology in euchromatin regions of tomato, potato
      and pepper with special attention for the long arm of chromosome 2 (2L).
      Molecular organization and colinear junctions were delineated using multi-color
      BAC FISH analysis and comparative sequence alignment. We found large-scale
      rearrangements including inversions and segmental translocations that were not
      reported in previous comparative studies. Some of the structural rearrangements
      are specific for the tomato clade, and differentiate tomato from potato, pepper
      and other Solanaceous species. Although local gene vicinity is largely preserved,
      there are many small-scale synteny perturbations. Gene adjacency in the aligned
      segments was frequently disrupted for 47% of the ortholog pairs as a result of
      gene and LTR retrotransposon insertions, and occasionally by single gene
      inversions and translocations. Our data also suggests that long distance intra
      chromosomal rearrangements and local gene rearrangements have evolved frequently
      during speciation in the Solanum genus, and that small changes are more prevalent
      than large-scale differences. The occurrence of sonata and harbinger transposable
      elements and other repeats near or at junction breaks is considered in the light
      of repeat-mediated rearrangements and a reconstruction scenario for an ancestral
      2L topology is discussed.

PMID- 22463057
TI  - Effect of hydrocortisone therapy on severe leaky lung syndrome in ventilated
      preterm infants.
AB  - BACKGROUND: The aim of this study was (i) to determine the incidence and risk
      factors of severe leaky lung syndrome (sLLS), persistent pulmonary edema
      characterized by massive tracheal secretions and resistance to surfactant
      therapy, in extremely low gestational age newborns requiring ventilatory support;
      and (ii) to evaluate the effects of hydrocortisone (HC) therapy for sLLS on
      tracheal aspirate fluid (TAF) volume and beta2-microglobulin levels in TAF.
      METHODS: Infants born at <28 weeks gestation requiring ventilation beyond day of
      life (DOL) 7 were included. Daily TAF volume changes were assessed using a TAF
      scoring system. Levels of TAF beta2-microglobulin, an indicator of capillary
      leakage, were measured at DOL0, 7, before, and 4 days after starting HC therapy
      (started at 4 mg/kg/day; tapered for 1-3 weeks). RESULTS: Of the 54 infants
      enrolled, 24 (44%) were diagnosed with sLLS. Lower gestational age, lower
      birthweight, and higher TAF beta2-microglobulin levels at DOL7 were independent
      risk factors for sLLS. Seventeen infants with sLLS received HC therapy starting
      at DOL17 (median), with subsequent decreases in TAF volume and beta2
      microglobulin levels. CONCLUSIONS: The incidence of sLLS, as defined in this
      study, was 44% in extremely low gestational age newborns requiring ventilator
      support beyond a week. HC therapy effectively reduced TAF volume and beta2
      microglobulin levels, suggesting suppression of increased permeability of
      pulmonary capillaries in infants with sLLS.

PMID- 22463058
TI  - Unfaithful individuals are less likely to practice safer sex than openly
      nonmonogamous individuals.
AB  - INTRODUCTION: Given the prevalence and harm of sexually transmitted infections
      (STIs), there is a need to examine safer sex strategies in the context of
      romantic relationships and extradyadic sexual encounters. Sexual infidelity is
      associated with a variety of detrimental psychosocial outcomes; however, little
      research has addressed the sexual health ramifications of sexually unfaithful
      partners and members of other high-risk nonmonogamous lifestyles. AIMS: To
      determine whether sexually unfaithful individuals or "negotiated nonmonogamous"
      individuals are more likely to engage in sexual health risk reduction behaviors
      during extradyadic encounters and with their primary partner. METHOD: Data were
      collected via an anonymous Internet-based study. Several hundred sexually
      unfaithful individuals and individuals with a negotiated nonmonogamy agreement
      completed a sexual health questionnaire. MAIN OUTCOMES MEASURES: Self-reported
      measures of risk reduction behaviors within the primary relationship and risk
      reduction behaviors during the extradyadic encounter were assessed. RESULTS:
      Sexually unfaithful participants demonstrated significantly lower rates of
      protective sexual health behaviors both within their primary partnerships and
      during their extradyadic sexual encounters. Sexually unfaithful participants were
      also less likely to engage in frequent STI testing, and less likely to discuss
      safer sex concerns with new partners. CONCLUSIONS: These data add to the
      literature on the negative effects of sexual unfaithfulness. Understanding rates
      of nonengagement in safer sex strategies will be helpful to those who lead
      efforts to increase condom use and other preventive STI measures.

PMID- 22463059
TI  - Lower rim guanidinocalix[4]arenes: macrocyclic nonviral vectors for cell
      transfection.
AB  - Guanidinium groups were introduced through a spacer at the lower rim of
      calix[4]arenes in the cone conformation to give new potential nonviral vectors
      for gene delivery. Several structural modifications were explored, such as the
      presence or absence of a macrocyclic scaffold, lipophilicity of the backbone,
      length of the spacer, and nature of the charged groups, in order to better
      understand the factors which affect the DNA condensation ability and transfection
      efficiency of these derivatives. The most interesting compound was a
      calix[4]arene unsubstituted at the upper rim and having four guanidinium groups
      linked at the lower rim through a three carbon atom spacer. This compound, when
      formulated with DOPE, showed low toxicity and transfection efficiency higher than
      the commercially available lipofectamine LTX in the treatment of human
      Rhabdomiosarcoma and Vero cells. Most of the investigated compounds showed a
      tendency to self-aggregate in pure water or in the presence of salts, as
      evidenced by NMR and AFM studies, and it was found that the ability to condense
      DNA plasmids in nanometric globules is a necessary but not sufficient condition
      for transfection. The superiority of macrocyclic vectors over linear Gemini-type
      analogues and of guanidinium compared to other ammonium head groups in
      determining the biological activity of the vectors was also ascertained. 

PMID- 22463060
TI  - Improved negative selection protocol for Plasmodium berghei in the rodent
      malarial model.
AB  - An improved methodology is presented here for transgenic Plasmodium berghei lines
      that express the negative selectable marker yFCU (a bifunctional protein that
      combines yeast cytosine deaminase and uridyl phosphoribosyl transferase (UPRT))
      and substitutes delivery of selection drug 5-fluorocytosine (5FC) by
      intraperitoneal injection for administration via the drinking water of the mice.
      The improved methodology is shown to be as effective, less labour-intensive,
      reduces animal handling and animal numbers required for successful selection
      thereby contributing to two of the "three Rs" of animal experimentation, namely
      refinement and reduction.

PMID- 22463062
TI  - Age and sex variation in prevalence of chronic medical conditions in older
      residents of U.S. nursing homes.
AB  - OBJECTIVES: To investigate patterns in prevalences of chronic medical conditions
      over the age span of long-term stay nursing home residents and between the sexes
      with data from the 2004 National Nursing Home Survey (NNHS). DESIGN:
      Retrospective, cross-sectional study. SETTING: U.S. nursing homes. PARTICIPANTS:
      Nationally representative sample comprising 11,788 long-term stay residents
      (3,003 (25%) men, 8,785 (75%) women) aged 65 and older. MEASUREMENTS: Clinical
      Classifications Software was used to group International Classification of
      Diseases, Ninth Revision, codes to identify the 20 most-prevalent chronic medical
      conditions. SAS survey procedures were used to account for design effects of
      stratification and clustering to generate nationally representative estimates of
      prevalences of medical conditions. RESULTS: Average age was 84, with women older
      than men (85 vs 81, P = .02) and 67% of women aged 80 to 95. Women required more
      assistance with activities of daily living. The most frequent chronic medical
      conditions were hypertension (men 53%, women 56%), dementia (men 45%, women 52%),
      depression (men 31%, women 37%), arthritis (men 26%, women 35%), diabetes
      mellitus (men 26%, women 23%), gastroesophageal reflux disease (GERD) (men 23%,
      women 23%), atherosclerosis (men 24%, women 20%), congestive heart failure (CHF)
      (men 18%, women 21%), cerebrovascular disease (CVD) (men 24%, women 19%), and
      anemia (men 17%, women 20%). Sex differences in prevalences existed for all but
      constipation, GERD, and hypertension. Diabetes mellitus, CVD, and lipid disorders
      decreased with age in men and women. Atrial fibrillation, anemia, arthritis, CHF,
      dementia, and thyroid disease increased with age in men and women. Age-related
      patterns differed between the sexes for diabetes mellitus, hypertension, and
      Parkinson's disease. CONCLUSION: The profile of chronic medical conditions varies
      over the age span of nursing home residents and differs between men and women.
      This knowledge should guide educational and care efforts in long-term care.

PMID- 22463063
TI  - Diagnostic accuracy of computed tomography pulmonary angiography and magnetic
      resonance imaging for an acute pulmonary embolism.

PMID- 22463064
TI  - Mutualistic interactions between vitamin B12 -dependent algae and heterotrophic
      bacteria exhibit regulation.
AB  - Many algae are auxotrophs for vitamin B(12)  (cobalamin), which they need as a
      cofactor for B(12) -dependent methionine synthase (METH). Because only
      prokaryotes can synthesize the cobalamin, they must be the ultimate source of the
      vitamin. In the laboratory, a direct interaction between algae and heterotrophic
      bacteria has been shown, with bacteria supplying cobalamin in exchange for fixed
      carbon. Here we establish a system to study this interaction at the molecular
      level. In a culture of a B(12) -dependent green alga Chlamydomonas nivalis, we
      found a contaminating bacterium, identified by 16S rRNA analysis as Mesorhizobium
      sp. Using the sequenced strain of M. loti (MAFF303099), we found that it was able
      to support the growth of B(12) -dependent Lobomonas rostrata, another green alga,
      in return for fixed carbon. The two organisms form a stable equilibrium in terms
      of population numbers, which is maintained over many generations in semi
      continuous culture, indicating a degree of regulation. However, addition of
      either vitamin B(12)  or a carbon source for the bacteria perturbs the
      equilibrium, demonstrating that the symbiosis is mutualistic and facultative.
      Chlamydomonas reinhardtii does not require B(12)  for growth because it encodes a
      B(12) -independent methionine synthase, METE, the gene for which is suppressed by
      addition of exogenous B(12) . Co-culturing C. reinhardtii with M. loti also
      results in reduction of METE expression, demonstrating that the bacterium can
      deliver the vitamin to this B(12) -independent alga. We discuss the implications
      of this for the widespread distribution of cobalamin auxotrophy in the algal
      kingdom.

PMID- 22463065
TI  - The co-occurrence of non-suicidal self-injury and attempted suicide among
      adolescents: distinguishing risk factors and psychosocial correlates.
AB  - Although attempted suicide and non-suicidal self-injury (NSSI) are distinct
      behaviors differing in intent, form, and function, the behaviors co-occur at a
      high rate in both adults and adolescents. Researchers have begun to investigate
      the association between attempted suicide and NSSI among adolescents. The purpose
      of this paper is to present current research on this association. First, we
      discuss definitional issues associated with self-injurious behaviors. Next, we
      present research on the co-occurrence of attempted suicide and NSSI, including
      prevalence and associations with self-injury characteristics. We then discuss
      psychosocial variables associated with engaging in both NSSI and attempted
      suicide or one type of self-injury alone. Finally, we present the research to
      date on risk factors uniquely associated with either attempted suicide or NSSI.
      Implications for mental health professionals and future avenues of research are
      discussed.

PMID- 22463066
TI  - A national in-patient prescription chart: the experience in Wales 2004-2012.

PMID- 22463068
TI  - Evaluation of polyphenolic fraction isolated from aerial parts of Tribulus
      pterocarpus on biological properties of blood platelets in vitro.
AB  - The antiplatelet and antioxidative activity of polyphenolic fraction isolated
      from aerial parts of Tribulus pterocarpus in blood platelets stimulated by
      thrombin was studied. Thrombin as a strong physiological agonist induces the
      enzymatic peroxidation of endogenous arachidonic acid, the formation of different
      reactive oxygen species, including superoxide anion radicals ([Formula: see
      text](.)) and the platelet aggregation. Therefore, the aim of our study was to
      assess if the polyphenolic fraction from aerial parts of T. pterocarpus may
      change the biological properties of blood platelets activated by thrombin. We
      used cytochrome c reduction method to test the ability of this fraction to change
      [Formula: see text](.) generation in platelets. Arachidonic acid metabolism was
      measured by the level of thiobarbituric acid reactive substances (TBARS) and by
      the production of 8-epi-prostaglandin (8-EPI) F(2). Moreover, we determined the
      effects of the fraction on blood platelet aggregation induced by thrombin. We
      observed that the polyphenolic fraction from T. pterocarpus reduced [Formula: see
      text](.), 8-EPI and TBARS production in these cells. The ability of the fraction
      to decrease the [Formula: see text](.) generation in blood platelets supports the
      importance of free radicals in platelet functions, including aggregation process.
      This study may suggest that the tested plant fraction might be a good candidate
      for protecting blood platelets against changes of their biological functions,
      which may be associated with the pathogenesis of different cardiovascular
      disorders.

PMID- 22463069
TI  - Cohort mortality study of roofing granule mine and mill workers. Part I:
      Estimation of historical crystalline silica exposures.
AB  - A study was conducted to construct a job exposure matrix for the roofing granule
      mine and mill workers at four U.S. plants. Each plant mined different minerals
      and had unique departments and jobs. The goal of the study was to generate
      accurate estimates of the mean exposure to respirable crystalline silica for each
      cell of the job exposure matrix, that is, every combination of plant, department,
      job, and year represented in the job histories of the study participants. The
      objectives of this study were to locate, identify, and collect information on all
      exposure measurements ever collected at each plant, statistically analyze the
      data to identify deficiencies in the database, identify and resolve questionable
      measurements, identify all important process and control changes for each plant
      department-job combination, construct a time line for each plant-department
      combination indicating periods where the equipment and conditions were unchanged,
      and finally, construct a job exposure matrix. After evaluation, 1871 respirable
      crystalline silica measurements and estimates remained. The primary statistic of
      interest was the mean exposure for each job exposure matrix cell. The average
      exposure for each of the four plants was 0.042 mg/m(3) (Belle Mead, N.J.), 0.106
      mg/m(3) (Corona, Calif.), 0.051 mg/m(3) (Little Rock, Ark.), and 0.152 mg/m(3)
      (Wausau, Wis.), suggesting that there may be substantial differences in the
      employee cumulative exposures. Using the database and the available plant
      information, the study team assigned an exposure category and mean exposure for
      every plant-department-job and time interval combination. Despite a fairly large
      database, the mean exposure for > 95% of the job exposure matrix cells, or
      specific plant-department-job-year combinations, were estimated by analogy to
      similar jobs in the plant for which sufficient data were available. This approach
      preserved plant specificity, hopefully improving the usefulness of the job
      exposure matrix.

PMID- 22463070
TI  - Alkyne and reversible nitrile activation: N,N'-diamidocarbene-facilitated
      synthesis of cyclopropenes, cyclopropenones, and azirines.
AB  - We report the synthesis of a variety of diamidocyclopropenes by combining an
      isolable and readily accessible N,N'-diamidocarbene (DAC) with a range of alkynes
      (nine examples, 68-97% yield). Subsequent hydrolysis of selected cyclopropenes
      afforded the corresponding cyclopropenones or alpha,beta-unsaturated acids,
      depending on the reaction conditions. In addition, the combination of a DAC with
      alkyl or aryl nitriles was found to form 2H-azirines in a reversible manner (four
      examples, K(eq) = 4-72 M(-1) at 30  degrees C in toluene).

PMID- 22463071
TI  - Use of the integrated health interview series: trends in medical provider
      utilization (1972-2008).
AB  - The Integrated Health Interview Series (IHIS) is a public data repository that
      harmonizes four decades of the National Health Interview Survey (NHIS). The NHIS
      is the premier source of information on the health of the U.S. population. Since
      1957 the survey has collected information on health behaviors, health conditions,
      and health care access. The long running time series of the NHIS is a powerful
      tool for health research. However, efforts to fully utilize its time span are
      obstructed by difficult documentation, unstable variable and coding definitions,
      and non-ignorable sample re-designs. To overcome these hurdles the IHIS, a freely
      available and web-accessible resource, provides harmonized NHIS data from 1969
      2010. This paper describes the challenges of working with the NHIS and how the
      IHIS reduces such burdens. To demonstrate one potential use of the IHIS we
      examine utilization patterns in the U.S. from 1972-2008.

PMID- 22463072
TI  - How the charge-neutrality level of interface states controls energy level
      alignment in cathode contacts of organic bulk-heterojunction solar cells.
AB  - Electronic equilibration at the metal-organic interface, leading to equalization
      of the Fermi levels, is a key process in organic optoelectronic devices. How the
      energy levels are set across the interface determines carrier extraction at the
      contact and also limits the achievable open-circuit voltage under illumination.
      Here, we report an extensive investigation of the cathode energy equilibration of
      organic bulk-heterojunction solar cells. We show that the potential to balance
      the mismatch between the cathode metal and the organic layer Fermi levels is
      divided into two contributions: spatially extended band bending in the organic
      bulk and voltage drop at the interface dipole layer caused by a net charge
      transfer. We scan the operation of the cathode under a varied set of conditions,
      using metals of different work functions in the range of ~2 eV, different
      fullerene acceptors, and several cathode interlayers. The measurements allow us
      to locate the charge-neutrality level within the interface density of sates and
      calculate the corresponding dipole layer strength. The dipole layer withstands a
      large part of the total Fermi level mismatch when the polymer:fullerene blend
      ratio approaches ~1:1, producing the practical alignment between the metal Fermi
      level and the charge-neutrality level. Origin of the interface states is linked
      with fullerene reduced molecules covering the metal contact. The dipole
      contribution, and consequently the band bending, is highly sensitive to the
      nature and amount of fullerene molecules forming the interface density of states.
      Our analysis provides a detailed picture of the evolution of the potentials in
      the bulk and the interface of the solar cell when forward voltage is applied or
      when photogeneration takes place.

PMID- 22463073
TI  - Antioxidant properties of humic substances.
AB  - Humic substances (HS) are heterogeneous, redox-active organic macromolecules.
      While electron transfer to and from HS under reducing conditions is well
      investigated, comparatively little is known on the electron donating (i.e.,
      antioxidant) properties of HS under oxic conditions. In this work, the electron
      donating capacities (EDCs) of terrestrial and aquatic HS were quantified by
      mediated electrochemical oxidation over a wide range of pH values and applied
      redox potentials (E(h)) using 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic
      acid) as an electron transfer mediator. Electrochemical oxidation of three model
      humic acids (HAs) was largely irreversible, and the EDCs of these HAs increased
      with increasing E(h) and pH. These results suggest that HS contain a wide variety
      of moieties that are oxidized at different potentials and that, upon oxidation,
      release protons and undergo irreversible follow-up reactions. At a given pH and
      E(h), the EDCs of the HS correlated well with their titrated phenol contents
      suggesting phenolic moieties as major electron donating groups in HS. Comparing
      the EDCs of 15 HS with their electron accepting capacities (EACs), aquatic HS had
      higher EDCs and lower EACs than terrestrial HS of comparable aromaticities. These
      results indicate that oxidative transformation of HS in the environment results
      in a depletion of electron donating phenolic moieties with antioxidant properties
      relative to the electron accepting quinone moieties.

PMID- 22463074
TI  - Base Adducts of a-Ketoenolates. VII. Electron Paramagnetic Resonance Studies of
      Some Fluxional 1,1,1,5,5,5-Hexafluoro-2,4-pentadionatocopper(II) Complexes.

PMID- 22463076
TI  - Endoscopic-assisted electrohydraulic shockwave lithotripsy in standing sedated
      horses.
AB  - OBJECTIVE: To report use of transendoscopic electrohydraulic shockwave
      lithotripsy for fragmentation of urinary calculi in horses. STUDY DESIGN: Case
      series. ANIMALS: Male horses (n = 21). METHODS: Fragmentation of cystic calculi
      (median, 6 cm diameter; range, 4-11 cm diameter) was achieved by transurethral
      endoscopy in standing sedated horses using an electrohydraulic shockwave fiber
      introduced through the biopsy channel of an endoscope. The fiber was advanced
      until it contacted the calculus. Repeated activation of the fiber was used to
      disrupt the calculus into fragments <1 cm diameter. Visibility within the bladder
      was maintained by repeated lavage with saline solution. RESULTS: Complete
      calculus removal was achieved in 20 horses (95%) with mean total surgical time of
      168.6 minutes (range, 45-450). In the 20 horses with single calculi, 1-6 sessions
      were required to completely fragment the calculus. Except for 1 horse, in which
      perineal urethrotomy was eventually performed for complete fragment removal,
      fragments calculi were excreted via the urethra. Postoperative complications
      included hematuria because of severe mucosal erosion (n = 2), dysuria because of
      a trapped urethral fragment (2), small amount of urinary debris (1). One horse
      was euthanatized because of bladder rupture. Complete clearance of calculi and
      urinary debris was confirmed endoscopically 20 (3-45) days after the last
      session. Telephone follow-up (mean, 18.8 months; range, 7-24 months) revealed
      that horses had returned to previous activity levels without recurrence of
      clinical signs. CONCLUSIONS: Transendoscopic electrohydraulic lithotripsy appears
      to be an effective method for fragmentation of low-density calcium carbonate
      cystic calculi in male horses.

PMID- 22463075
TI  - Features of two proteins of Leptospira interrogans with potential role in host
      pathogen interactions.
AB  - BACKGROUND: Leptospirosis is considered a re-emerging infectious disease caused
      by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have
      the ability to survive and disseminate to multiple organs after penetrating the
      host. Leptospires were shown to express surface proteins that interact with the
      extracellular matrix (ECM) and to plasminogen (PLG). This study examined the
      interaction of two putative leptospiral proteins with laminin, collagen Type I,
      collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and
      C4bp. RESULTS: We show that two leptospiral proteins encoded by LIC11834 and
      LIC12253 genes interact with laminin in a dose - dependent and saturable mode,
      with dissociation equilibrium constants (KD) of 367.5 and 415.4 nM, respectively.
      These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for
      LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced
      Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand
      participate in this interaction. The Lsa33 is also PLG - binding receptor, with a
      KD of 23.53 nM, capable of generating plasmin in the presence of an activator.
      Although in a weak manner, both proteins interact with C4bp, a regulator of
      complement classical route. In silico analysis together with proteinase K and
      immunoflorescence data suggest that these proteins might be surface exposed.
      Moreover, the recombinant proteins partially inhibited leptospiral adherence to
      immobilized laminin and PLG. CONCLUSIONS: We believe that these multifunctional
      proteins have the potential to participate in the interaction of leptospires to
      hosts by mediating adhesion and by helping the bacteria to escape the immune
      system and to overcome tissue barriers. To our knowledge, Lsa33 is the first
      leptospiral protein described to date with the capability of binding laminin, PLG
      and C4bp in vitro.

PMID- 22463077
TI  - Suicidal expressions among young people in Nicaragua and Cambodia: a cross
      cultural study.
AB  - BACKGROUND: Whereas prevalence of suicidal expressions among young people is
      fairly similar in different countries, less is known about associated risk
      factors. This study compares young people in Nicaragua and Cambodia to examine if
      the pattern of association between mental health problems and suicidal
      expressions differs. METHODS: 368 and 316 secondary school students, from each
      country respectively, participated. Self-reported suicidal expressions, exposure
      to suicidal behavior in significant others and mental health problems among the
      students were measured using Attitude Towards Suicide (ATTS) and the Youth Self
      Report (YSR) questionnaires. RESULTS: Prevalence of serious suicidal expressions
      (plans and attempts) during recent year, did not differ between countries.
      Cambodian young people scored significantly higher on all eight YSR-syndromes,
      except for withdrawn/depressed. In Nicaragua, all YSR-syndromes were
      significantly associated with serious suicidal expressions in both genders
      compared to Cambodia where only one syndrome showed an association in each
      gender; Withdrawn/depressed among girls and Somatic complaints among boys.
      Associations between being exposed to suicide among significant others and
      serious suicidal expressions also differed between Cambodia and Nicaragua.
      CONCLUSIONS: While the magnitude of serious suicidal expressions is similar
      between these structurally similar but culturally different countries,
      determinants behave differently. Qualitative studies are warranted to further
      explore cultural specific determinants for suicidal expressions among young
      people.

PMID- 22463080
TI  - Identifying aquifer type in fractured rock aquifers using harmonic analysis.
AB  - Determining aquifer type, unconfined, semi-confined, or confined, by drilling or
      performing pumping tests has inherent problems (i.e., cost and complex field
      issues) while sometimes yielding inconclusive results. An improved method to cost
      effectively determine aquifer type would be beneficial for hydraulic mapping of
      complex aquifer systems like fractured rock aquifers. Earth tides are known to
      influence water levels in wells penetrating confined aquifers or unconfined
      thick, low-porosity aquifers. Water-level fluctuations in wells tapping confined
      and unconfined aquifers are also influenced by changes in barometric pressure.
      Harmonic analyses of water-level fluctuations of a thick (~1000 m) carbonate
      aquifer located in south-central Oklahoma (Arbuckle-Simpson aquifer) were
      utilized in nine wells to identify aquifer type by evaluating the influence of
      earth tides and barometric-pressure variations using signal identification. On
      the basis of the results, portions of the aquifer responded hydraulically as each
      type of aquifer even though there was no significant variation in
      lithostratigraphy. The aquifer type was depth dependent with confined conditions
      becoming more prevalent with depth. The results demonstrate that harmonic
      analysis is an accurate and low-cost method to determine aquifer type.

PMID- 22463079
TI  - The cyclophilin ROC1 links phytochrome and cryptochrome to brassinosteroid
      sensitivity.
AB  - Although multiple photoreceptors converge to control common aspects of seedling
      de-etiolation, we are relatively ignorant of the genes acting at or downstream of
      their signalling convergence. To address this issue we screened for mutants under
      a mixture of blue plus far-red light and identified roc1-1D. The roc1-1D mutant,
      showing elevated expression of the ROTAMASE CYCLOPHILIN 1 (ROC1/AtCYP18-3) gene,
      and partial loss-of function roc1 alleles, has defects in phytochrome A (phyA)-,
      cryptochrome 1 (cry1)- and phytochrome B (phyB)-mediated de-etiolation, including
      long hypocotyls under blue or far-red light. These mutants show elevated
      sensitivity to brassinosteroids in the light but not in the dark. Mutations at
      brassinosteroid signalling genes and the application of a brassinosteroid
      synthesis inhibitor eliminated the roc1 and roc1-D phenotypes. The roc1 and roc1
      D mutants show altered patterns of phosphorylation of the transcription factor
      BES1, a known point of control of sensitivity to brassinosteroids, which
      correlate with the expression levels of genes directly targeted by BES1. We
      propose a model where perception of light by phyA, cry1 or phyB activates ROC1
      (at least in part by enhancing its expression). This in turn reduces the
      intensity of brassinosteroid signalling and fine-tunes seedling de-etiolation.

PMID- 22463081
TI  - Estrogen receptor alpha and beta in esophageal squamous cell carcinoma.
AB  - A gender difference has been reported in the morbidity of esophageal squamous
      cell carcinoma (ESCC). Estrogens have been proposed to play a role in this
      difference but the details have not yet been clarified. Therefore, in the present
      study, we examined the status of estrogen receptor (ER)alpha and ERbeta in 90
      Japanese ESCC patients. ERalpha and ERbeta immunoreactivity was detected in the
      nuclei of ESCC cells (41.1 and 97.8%, respectively). There was a significant
      positive association between the ERbeta H score and histological differentiation
      (P = 0.0403), TNM-pM (LYM) (P = 0.00164) and Ki67/MIB1 LI of carcinoma cells (P =
      0.0497, r = 0.207). In addition, the ERbeta status of carcinoma cells was
      significantly correlated with unfavorable clinical outcome of the patients.
      Multivariate analysis further revealed the ERbeta status in carcinoma cells as an
      independent unfavorable prognostic factor of these patients. We further examined
      the effects of estrogen treatment on ESCC cell line (ECGI-10) transfected with
      ERalpha or ERbeta in vitro. The number of ECGI-10 transfected with ERbeta was
      increased by estradiol or ERbeta specific agonist but estradiol did not exert any
      effect upon the cell number of ECGI-10 transfected with ERalpha. In summary, the
      results of the present study clearly demonstrate that the status of ERbeta in
      ESCC was closely associated with the unfavorable prognosis, possibly through
      altering cell proliferation of carcinoma cells.

PMID- 22463082
TI  - Size dependent biodistribution and SPECT imaging of (111)In-labeled polymersomes.
AB  - Polymersomes, self-assembled from the block copolymer polybutadiene-block
      poly(ethylene glycol), were prepared with well-defined diameters between 90 and
      250 nm. The presence of ~1% of diethylene triamine penta acetic acid on the
      polymersome periphery allowed to chelate radioactive (111)In onto the surface and
      determine the biodistribution in mice as a function of both the polymersome size
      and poly(ethylene glycol) corona thickness (i.e., PEG molecular weight). Doubling
      the PEG molecular weight from 1 kg/mol to 2 kg/mol did not change the blood
      circulation half-life significantly. However, the size of the different
      polymersome samples did have a drastic effect on the blood circulation times. It
      was found that polymersomes of 120 nm and larger become mostly cleared from the
      blood within 4 h, presumably due to recognition by the reticuloendothelial
      system. In contrast, smaller polymersomes of around 90 nm circulated much longer.
      After 24 h more than 30% of the injected dose was still present in the blood
      pool. This sharp transition in blood circulation kinetics due to size is much
      more abrupt than observed for liposomes and was additionally visualized by
      SPECT/CT imaging. These findings should be considered in the formulation and
      design of polymersomes for biomedical applications. Size, much more than for
      liposomes, will influence the pharmacokinetics, and therefore, long circulating
      preparations should be well below 100 nm.

PMID- 22463083
TI  - Docking studies of novel pyrazinopyridoindoles class of antihistamines with the
      homology modelled H(1)-receptor.
AB  - Histamine is an important neurotransmitter as it controls a multitude of
      physiological functions by activating specific receptors on target cells. It
      exerts its effects by binding to four different histamine receptors (H(1)-H(4)),
      which all belong to the large family of G protein-coupled receptors (GPCRs).
      Research and development of H(1) ligand has largely focused on antagonists which
      are used for their anti-allergy effects in the periphery. Recent understanding of
      the clinical importance of H(1) receptors in brain, however, suggests the
      pharmacotherapeutic potential of H(1) agonists in neurodegenerative and
      neuropsychiatric disorders. Despite the therapeutic importance of the H(1)
      receptor, for many years the molecular features of the H(1) receptor protein had
      been unknown. In view of the recently reported crystal structure of human H(1)
      receptor and in continuation of our work on 3D-pharmacophore on antihistamine
      H(1) and homology model of histamine H(1) receptor, docking studies have been
      carried out on some promising pyrazinopyridoindole class of antihistamine H(1),
      including two outliers, to validate our earlier reported models/hypotheses on
      H(1)-receptor, where a good explanation between estimated and observed activities
      has been obtained. In addition, the docking study also provided insights about
      the optimal activity of the outliers, for which no explanation was reported
      previously.

PMID- 22463084
TI  - Effect of ammonium-iron-hexa-cyanoferrate and of the covariates age, gender,
      weight, season and calendar time on radiocaesium contamination of wild boars
      living in the wild in Bavaria.
AB  - Feed with Ammonium-iron-hexa-cyanoferrate (AFCF; 1250 mg AFCF/kg) was fed between
      March 2009 and March 2011 to wild boars in a territory of 4.5 km(2) (experimental
      group, EXP). One hundred and forty similar territories in the same county (500
      km(2) , spruce forest, agriculture) served as control (CON). Data for comparison
      from all territories were available from March 2005 to March 2011. Wild boars
      could move between, into and from the territories. Lean skeletal muscle meat (500
      g) of all wild boars that were killed by humans (hunting and traffic accidents)
      was investigated for gamma-radiation from (137) Cs with a becquerel monitor with
      a sodium iodide scintillator crystal (range of detection 20-9999 Bq/kg). The wild
      boars were weighed, and gender and age were determined. For the analyses of
      effects, multivariable regression models were fitted with the (137) Cs
      concentration as response variable. There was a significant difference between
      the (137) Cs contamination of wild boars from CON (563 +/- 932 Bq/kg meat, n =
      1253) and EXP (236 +/- 276 Bq/kg meat; n = 45). (137) Cs contamination decreased
      with increasing body weight by -5 Bq/kg meat/kg body weight increase (p < 0.05).
      Females had higher Bq measurements than males (by +80 Bq/kg meat, p < 0.05).
      Piglets were lower than adults, but turn-coats higher. From November to May,
      contamination was higher (by +500 to +600 Bq/kg meat, p < 0.05) than during the
      rest of the year. In 2010, contamination was higher (by +200 to + 300 Bq/kg meat,
      p < 0.05) in comparison with the other years under observation. When all
      covariates were controlled for, the effect of AFCF was highly significant.
      Interaction analyses showed that the intervention decreased (137) Cs
      contamination by -500 Bq/kg meat during November to May and by -200 Bq/kg meat
      during the rest of the year. In summary, AFCF feeding reduces (137) Cs
      contamination of wild boars living in the wild significantly, particularly during
      the season from November to May.

PMID- 22463085
TI  - Plasminogen activation and thrombolysis for ischemic stroke.
AB  - The plasminogen-activating enzyme system has been exploited and harnessed for
      therapeutic thrombolysis for nearly three decades. Tissue-type plasminogen
      activator is still the only thrombolytic agent approved for patients with
      ischemic stroke. While tissue-type plasminogen activator-induced thrombolysis is
      proven to be of clear benefit in these patients if administered within 4.5 h
      poststroke onset, it is surprisingly underused in clinics despite international
      guidelines and improved acute stroke systems, a situation that requires urgent
      attention. While tissue-type plasminogen activator has also been shown to have
      unforeseen roles in the brain that have presented new challenges, tissue-type
      plasminogen activator and related fibrinolytic agents are currently being
      assessed over extended time frames. This review will focus on the therapeutic
      experience and controversies of tissue-type plasminogen activator. Furthermore,
      we will also provide an overview of recent and current trials assessing tissue
      type plasminogen activator and related thrombolytic agents as well as novel
      approaches for the treatment of ischemic stroke.

PMID- 22463086
TI  - [An overview of so far published analyses comparating the effectiveness of the
      treatment with insulin pump and multiple daily injections in type 1 diabetes
      mellitus].
AB  - The paper brings an overview of published systematic reviews and meta-analyses
      concerning the evaluation of the effectiveness of the treatment with insulin pump
      (CSII) in comparison with multiple daily injections (MDI) in type 1 diabetes
      mellitus. According to found works CSII leads to slightly lower levels of
      glycosylated hemoglobin (HbA1c) in patients with type 1 diabetes mellitus against
      MDI. The levels of HbA1c and the variability of glycaemia during the day on MDI
      before an initiation of CSII should serve for the prediction of an effect of CSII
      in particular patient. Type 1 diabetics on CSII have less often hypoglycaemia,
      higher flexibility of their daily regime and thus higher satisfaction with their
      treatment against MDI. The daily doses of insulin decrease. The weight of
      patients is the same or slightly higher after the initiation of CSII. There were
      not enough information for the assesment of the frequency of adverse reactions.
      It is necessary to educate each patient not only how to manipulate the particular
      insulin pump, but also about general recommendations for the treatment of
      diabetes and the application of insulin.

PMID- 22463087
TI  - [Radioiodine 131I therapy of hyperthyroidism on an outpatient basis - safe,
      effective and economic option].
AB  - INTRODUCTION: Radioiodine 131I therapy of hyperthyroidism on an outpatient basis
      is widely accepted over the world. In Czech Republic, however, radioiodine
      therapy is still not enough used, and has been realized on an inpatient basis to
      date. Our work is the first analysis of the experiences with radioiodine therapy
      of hyperthyroidism on an outpatient basis in Czech Republic. METHODS: Capsule
      with 550 MBq of 131I was administered orally in 39 hyperthyroid patients (32
      women and 8 men, 21 with autoimmune Graves hyperthyroidism and 18 with toxic
      thyroid nodules, mean age 66.8 years). In 32 of them we evaluated effectiveness
      and complications of therapy after 12-42 months. We also compared financial costs
      of the radioiodine treatment on an outpatient basis with the treatment in
      hospitalization and with surgery. RESULTS: After the treatment, 9/32 (28 %)
      patients were euthyroid without thyrostatic/thyroxine treatment, 18/32 (60 %)
      patients were hypothyroid with thyroxine therapy, 2/32 (6 %) patients
      significantly decreased doses of thyrostatic drugs. In 2/32 (6 %) patients the
      treatment was ineffective. The effect of the treatment did not depend on the
      etiology and severity of hyperthyroidism, but decreased with thyroid volume.
      Patients with ineffective or only partially effective treatment had median of
      thyroid volume more than 40 ml. In 1 patient thyroid associated ophthalmopathy
      was moderately worsened. Other complications were not observed. If we compared
      financial costs in model with 1 patient, we found that the costs of radioiodine
      therapy on an outpatient basis (118.7 ?) comprise only 16 % of the costs of
      radioiodine therapy in hospitalization (728 ?) and only 25 % of the costs of
      surgery (475.6 ?). CONCLUSION: Radioiodine 131I is effective and safe in the
      treatment of hyperthyroidism and the therapy on an outpatient basis is much
      cheaper choice. The therapy with 131I on an outpatient basis is not suitable in
      patients with thyroid volume more than 40 ml.

PMID- 22463088
TI  - [Celiac disease - a missed diagnosis].
AB  - BACKGROUND: In Czech population celiac disease is diagnosed infrequently and on
      the contrary frequently too late. AIM: The present quality of diagnostics,
      therapy, follow-up and relation of celiacs to causal therapy has been evaluated.
      METHODS: A structured questionnaire was offered to celiacs followed at different
      out-patient departments (medicine, gastroenterology, dermatology, hematology, and
      endocrinology) of one institution (Central Military Hospital Prague) in the years
      2000-2010. The following topics were analyzed: the health care provided to
      probands before the diagnosis of celiac disease (number and speciality of
      involved physicians, symptoms and suggested conditions), methods of celiac
      disease diagnosis, screening of the disease in first degree relatives, compliance
      of gluten-free diet and its limiting factors. RESULTS: 102 (77.3%) out of 132
      distributed questionnaires were evaluated. The diagnosis of celiac disease
      remains a late issue. 36.8% of celiac patients were diagnosed after a period of
      more than 10 years of symptoms. Diarrhea has been frequently combined with
      extraintestinal symptoms (anemia, decreased body mass, depression, and
      osteoporosis). Gluten-free diet is an expensive dietary regimen and its adherence
      brings various restrictions to celiacs in every-day life. CONCLUSION: The present
      state of celiac disease diagnostics and follow-up requires interdisciplinary
      cooperation and increased interest of health and social care institutions
      including their leading representatives.

PMID- 22463089
TI  - [Virological sustained response to former young intravenous drug abusers with
      chronic hepatitis C treated by pegylated interferon-alpha plus ribavirin].
AB  - INTRODUCTION: The most risk group with high rate of infection of viral hepatitis
      C represents the former drug abusers (IDUs). OBJECTIVES: The objectives of the
      clinical study were to assess the sustained virological response (SVR) in the
      group of former IDUs with chronic hepatitis C (CHC) treated with pegylated
      interferon-alpha and ribavirin. PATIENTS AND METHODS: Of 293 previously untreated
      (naive) former IDUs with CHC who have started treatment, we assessed 239 (69
      women, 170 men) with an average age of 27 years who completed treatment and
      received a follow-up examination after 24 weeks. Prior to therapy abstinence to
      drug abuse 6 and more months has been required. The CHC has been diagnostics by
      the standard virological diagnostic tests, increased activity of aminotranferases
      (ALT) and histology of liver biopsy. Patients were treated with combined
      immunomodulatory therapy in the standard duration and standard regimen. SVR was
      considered if qualitative test HCV RNA was negative 24 weeks after the completion
      of the treatment. RESULTS: End-of-treatment virological response was in 224/94 %
      patients. Overall SVR rate was 95 %, 227 subjects had negative HCV RNA and only
      12 patients no response. During treatment there was a statistically significant
      decrease in ALT. Treatment was accompanied by the expected side effects.
      CONCLUSION: Young age, short duration of HCV infection, high prevalence of
      genotype 3 and low grade of liver fibrosis in majority of patients and good
      adherence of patients to treatment were crucial predictive factors resulting in
      high SVR.

PMID- 22463090
TI  - [Food craving symptoms in older school age children and its relation to body-mass
      index].
AB  - Recent findings show that food craving represents an important co-factor in
      overweight and obesity etiology and its severity represents a good predictor of
      relapse during active weight control. Child overweight and obesity also
      represents significant predictive factor of adulthood obesity and evidence about
      its incidence in children is therefore important. In order to achieve this
      evidence the indices of food craving has measured in 150 older school age
      children (54 boys and 96 girls; mean age 13.6 +/- 1.2). The food craving symptoms
      were measured by validated Czech translation of the General Food-Craving
      Questionnaire-Trait (G-FCQ-T). Body proportions of children were indexed by body
      mass index (BMI). BMI were assessed according to cut-off points BMI references
      from the Czech Republic. Results have shown that older school children have
      experience with food craving symptoms, and that intensity of these symptoms is
      significantly associated with BMI value (r = 0.55; p < 0.0001). Statistical
      analysis also revealed higher incidence of food craving symptoms intensity in
      girls. These findings provide basic normative data about food craving symptoms
      occurrence and intensity in older school age children group. Presented results
      also indirectly support the hypothesis that food craving could represent
      important co-factor in childhood obesity etiology. The consequences for obesity
      psychotherapy will be discussed.

PMID- 22463091
TI  - [Clinical implications of enlargement of left atrium].
AB  - Enlargement of left atrium (LA) has been shown to be a barometer of diastolic
      burden and a predictor of common cardiovascular outcomes such as atrial
      fibrillation, stroke, congestive heart failure, and cardiovascular death.
      Different methods exist for the assessment of LA size. The American Society of
      Echocardiography recommended LA volume and its indexed value assessed by 2
      dimensional echocardiography, to measure LA size. Current findings suggest that
      echocardiographically determined LA size may become an important clinical risk
      identifier in preclinical cardiovascular disease and should be assessed as a part
      of routine echocardiographic evaluation.

PMID- 22463092
TI  - [Haemostatic mechanisms in the process of atherotrombosis].
AB  - Hemostasis play an essentials role in protecting of vascular integrity and
      maintaining normal blood flow, and anatomically and functionally is entwined with
      the vasculature. The classic concept of atherosclerosis assigns a pivotal role to
      inflammation in the onset and progression of this disease. Accumulating data
      suggest an intimate cross-talk between hemostasis and inflammation, underscoring
      the role of both systems in many complex diseases, including atherothrombosis. An
      experimental data indicate that platelets and the coagulation system are
      important determinants of both atherogenesis and atherothrombosis. The hemostatic
      system is well known for its capacity to exert a multitude of actions on the
      vasculature. The current concept of a vulnerable plaque suggests that repeated
      plaque microruptures, followed by subclinical thrombosis, are critical for plaque
      growth and vulnerability.

PMID- 22463093
TI  - [Significance of urokinase and its inhibitors in the invasiveness and metastasing
      of malignant tumors].
AB  - Fibrinolysis is process, which leads to the degradation of fibrin to fibrin
      monomers. Fibrinolysis helps to regulate hemostasis and prevents the creation of
      inappropriately large thrombus, which could reduce blood flow to the bloodstream.
      The main enzyme involved in fibrinolysis is plasmin. Tissue plasminogen activator
      (tPA) and urokinase (uPA) are agents converting plasminogen into active plasmin,
      together with urokinase receptor (uPAR) and urokinase inhibitors (PAI 1, PAI 2,
      PAI 3 and protease nexin) form plasminogen activator system (PAS) which is among
      others also part of the metastatic cascade and significantly contributes to
      invasive growth and angiogenesis of malignant tumours. In contrast to tPA that is
      fundamental in fibrinolysis, uPA plays an essential role in tissue degradation as
      part of physiological and pathological processes. uPAR is a GPI
      (glycosylphosphatidylinositol)-anchored protein. The binding of uPA to uPAR
      results in activation of protein tyrosine kinase, protein kinase C and MAP
      kinase. At the same time, direct signalling pathway via Jak/STAT cascade
      utilising signalling transduction of Scr-like protein tyrosine kinase have also
      been described. uPAR expression is regulated by many growth factors, e.g. EGF,
      FGF-2 and HGF. It seems that individual PAS factors are involved in the process
      of rendering malignant tumors invasive. To what degree this influence is
      essential to specific malignancies, should be answered by further research. In
      the article the authors present a summary of findings about the interaction of
      fibrinolysis and tumor process, especially on the effects of urokinase and other
      activators and their inhibitors in metastasis of malignant tumors. The text
      contains information on the factors theirs introduction into practice is still
      the subject of numerous discussions, but in the future, individual PAS factors
      could play an important role in planning treatment strategies and also could
      become targets of targeted therapy.

PMID- 22463094
TI  - [Soft tissues, hormones and the skeleton].
AB  - Mechanical load activates bone modeling and increases bone strength. Thus
      physical activity is extremely important for overall bone health. Muscle volume
      and muscle contraction are closely related to bone mineral density in men and
      women, although these relationships are more significat in men. The muscle-bone
      unit has been defined as a functional system, in which both components are under
      control of the somatotropin-IGF-I system, androgens and D hormone. These
      endocrine systems play, via the muscle-bone unit, an important role in
      development of the skeleton and its stability in adulthood. That is why
      deficiency of any of these hormonal systems, or reduced physical activity (mainly
      in childhood) could seriously affect bone density and quality. Bone is also under
      control of adipose tissue, which modulates its metabolism via mechanical load and
      more importantly via adipocytokines (leptin, adiponectin and rezistin). Leptin
      increases bone formation by activation of osteoblasts. This direct effect of
      leptin is amplified by stimulation of the beta-1 adrenergic system, which
      inhibits the negative osteotropic effects of neuropeptide Y. On the other hand,
      leptin also activates beta-2 adrenergic receptors, which increase bone
      resorption. In humans, the overall osteo-anabolic effect of leptin tends to be
      dominant. Furthermore, leptin has a principal role in the start of puberty in
      girls and maturation, remodeling and development of the female skeleton.
      Adiponectin (and probably rezistin) has an unambiguous deteriorating effect on
      the skeleton. Further studies are needed to confirm the clinical importance of
      soft tissues relative to the integrity of the skeleton.

PMID- 22463095
TI  - [Medicines and thyroid gland].
AB  - From their primary pharmacological effect, many drugs may also affect the thyroid
      gland function or the results of thyroid function tests. In addition to the drugs
      with a known effect on thyroid gland, including thionamides, thyroid hormones,
      recombinant TSH, iodine, iodide, amiodarone, lithium and heparin, novel
      compounds, including tyrosin-kinase inhibitors, immunomodulators and cytokines
      also have adverse effects on the thyroid gland. Novel drugs are then associated
      with new types of adverse thyroid effects.

PMID- 22463096
TI  - [Chronic disseminated intravascular coagulation (DIC) markers in a patient with
      multiple angiomatosis during treatment with anti-angiogenics: interferon alpha,
      thalidomide and lenalidomide].
AB  - BACKGROUND: Multiple angiomatosis is a rare disease with angiomatous formations
      in multiple organs and tissues and associated with a risk of fatal bleeding. CASE
      DESCRIPTION: In this patient, the bones, pleural and peritoneal cavities and
      digestive tract were involved. The patient had long-term been administered
      zoledronate that provided relief from bone pain as early as after the second
      dose. The effect of antiangiogenics was evaluated on CT and MRI. Since
      angiomatous proliferation is associated with chronic disseminated intravascular
      coagulation (DIC) and anaemisation, blood count and fibrinogen as well as D-dimer
      and soluble fibrin monomer concentrations are also used to assess treatment
      response. RESULTS: Before treatment, D-dimer levels were in excess of 20 MUg/mL,
      fibrinogen 1.4 g/L and soluble fibrin monomers were at measurable levels. During
      treatment with interferon alpha at a dose of 6 million units 3 times a week with
      the dose reduction after 10 month, the median fibrinogen concentration increased
      to 1.5 (1.2-2.0) g/L, the median D-dimer levels declined to 17.2 (13.4-20.0)
      MUg/mL and fibrin monomers were still detectable. Thalidomide therapy (100
      mg/day) provided reduction in the median D-dimer levels to 6.07 (4.71-10.21)
      MUg/ml and increase in median fibrinogen concentration to 1.9 g/L; soluble fibrin
      monomers were unidentifiable. CT imaging suggested significant reduction of
      angiomatous mass. Progressing neuropathy required dose reduction of thalidomide
      to 50 mg/day, leading to D-dimer increase. Lenalidomide 10 mg/day provided an
      increase in median D-dimer concentration to 10.8 (10.8-17.35) and decline in the
      level of haemoglobin to a median of 124 (135-117) g/L. Soluble fibrin monomers
      became detectable again. Therefore, a low dose of lenalidomide 10 mg/day was
      combined with thalidomide 100 mg and, subsequently, 50 mg/day. Treatment with
      lenalidomide 10 mg and thalidomide 50 mg provided median D-dimer levels of 9.32
      and the disease has remained stable for 9 months. CONCLUSION: Thalidomide 100
      mg/day stabilized multiple angiomatosis better than interferon alfa. Thalidomide
      50 mg/day was insufficient to maintain disease stability. Lenalidomide at a dose
      of 10 mg was tolerated really well but this dose was insufficient to maintain low
      D-dimer levels and normal haemoglobin concentrations. The combination of
      lenalidomide 10 mg and thalidomide 50 mg daily stabilized the disease for 9
      months.

PMID- 22463097
TI  - [Good's syndrome (thymoma associated hypogammalobulinaemia) - 2 case reports].
AB  - Although tumours of the thymus are rare, they are common among neoplasms of the
      anterior superior mediastinum. They usually exhibit indolent behavior, but do
      have the capacity to invade surrouding structures. Their metastatic potential is
      low. Paraneoplastic complications including autoimmune disorders (frequently
      myastenia, cytopenia) or combined immunodeficiency are of clinical significance.
      Here we report two case reports of thymoma patients associated with secondary
      immunodeficiency known as Goods syndrom. The first case exhibited as symptomatic
      combinated immunodeficiency with oral lichen planus. Thymoma findings was
      accidental. Severity of immunodeficiency required long-term intravenous
      immunoglobulins supplementations, even after complete surgical resection. On the
      other hand, the second case manifested by signs of advanced local tumour growth.
      Antibiotic prophylaxis was selected as immunodeficiency treatment.

PMID- 22463098
TI  - [Summary of recommendations for the diagnosis and therapy of BCR/ABL-negative
      myeloproliferation of the Czech Working Group for Ph-negative myeloproliferative
      disease (CZEMP) of the Czech Hematologic Society CLS JEP ].

PMID- 22463099
TI  - Model selection for generalized estimating equations accommodating dropout
      missingness.
AB  - The generalized estimating equation (GEE) has been a popular tool for marginal
      regression analysis with longitudinal data, and its extension, the weighted GEE
      approach, can further accommodate data that are missing at random (MAR). Model
      selection methodologies for GEE, however, have not been systematically developed
      to allow for missing data. We propose the missing longitudinal information
      criterion (MLIC) for selection of the mean model, and the MLIC for correlation
      (MLICC) for selection of the correlation structure in GEE when the outcome data
      are subject to dropout/monotone missingness and are MAR. Our simulation results
      reveal that the MLIC and MLICC are effective for variable selection in the mean
      model and selecting the correlation structure, respectively. We also demonstrate
      the remarkable drawbacks of naively treating incomplete data as if they were
      complete and applying the existing GEE model selection method. The utility of
      proposed method is further illustrated by two real applications involving missing
      longitudinal outcome data.

PMID- 22463101
TI  - Why do we need improved mobility technology?

PMID- 22463100
TI  - Plasmodium yoelii blood-stage primes macrophage-mediated innate immune response
      through modulation of toll-like receptor signalling.
AB  - BACKGROUND: Toll-like receptors (TLRs) signalling is reported to be primed by the
      infection of human malaria parasite, Plasmodium falciparum. However, little is
      known about the regulation of macrophages TLR signalling by the infection of
      lethal or non-lethal strain of rodent malaria parasites. METHODS: BALB/c mice
      were infected with non-lethal strain Plasmodium yoelii 17XNL or lethal strain P.
      yoelii 17XL. Peritoneal macrophages were isolated to study its immune response to
      pRBC lysate, and TLRs (TLR2, TLR4, and TLR9) agonists, and the expression of TLRs
      and intracellular signalling molecules were also investigated by flow cytometry
      and semi-quantitive RT-PCR. RESULTS: The reactivity of peritoneal macrophages
      from the mice infected with lethal strain P. y 17XL or non-lethal strain P. y
      17XNL were enhanced to pRBC lysate, and TLR2, TLR4, and TLR9 agonists at one,
      three and five days post-infection. Of all the tested TLRs, only TLR2 was up
      regulated on peritoneal macrophages of mice infected with either strain. However,
      transcription of intracellular signalling molecules MyD88, IRAK-1, and TRAF-6 was
      significantly up-regulated in peritoneal macrophages from mice infected either
      with P. yoelii 17XL or P. yoelii 17XNL at one, three and five days post
      infection. However, the enhanced TLRs response of macrophage from P. yoelii 17XNL
      infected mice persisted for a much longer time than that from P. yoelii 17XL
      infected mice. CONCLUSION: Both P. yoelii 17XL and 17XNL strains could enhance
      the response of peritoneal macrophages to pRBC lysate and TLR agonists, through
      up-regulating the expression of TLR2 and intracellular signalling molecules
      MyD88, IRAK-1, and TRAF-6. In addition, prolonged high response of macrophage
      from P. yoelii 17XNL-infected mice might be associated with the more efficiently
      controlling of P. yoelii 17XNL growth in mice at early stage.

PMID- 22463102
TI  - Diannexin, an annexin A5 homodimer, binds phosphatidylserine with high affinity
      and is a potent inhibitor of platelet-mediated events during thrombus formation.
AB  - BACKGROUND: Shielding of procoagulant phosphatidylserine (PS) with annexin A5
      attenuates thrombosis, but annexin A5 (35.7 kDa) is rapidly cleared from the
      circulation. In contrast, Diannexin, a 73.1 kDa homodimer of annexin A5, has an
      extended half-life. OBJECTIVES: To quantify the affinity of Diannexin for PS,
      examine its interaction with activated platelets and determine its effects on
      platelet-mediated events during thrombus formation. METHODS: The affinities of
      Diannexin and annexin A5 for PS-containing lipid bilayers were compared using
      surface plasmon resonance, and binding to activated platelets was assessed by
      flow cytometry. Calibrated automated thrombography and thromboelastography were
      employed to study the effects of Diannexin on thrombin generation and platelet
      fibrin clot formation, respectively, whereas intravital videomicroscopy was used
      to examine its effect on platelet accumulation and activation after laser-induced
      injury to murine cremaster arterioles, and a tail tip bleeding model was used to
      explore its effects on hemostasis. RESULTS: Diannexin and annexin A5 bind PS with
      K(D) values of 0.6 and 5 nm, respectively, and both bind to the same
      subpopulation of PS-exposing platelets. Diannexin inhibited thrombin generation
      and platelet-fibrin clot formation in vitro at 10 nm (P<0.05-0.001 compared with
      control), and reduced platelet accumulation at 1 MUg g(-1) (P<0.05) and
      activation at 0.25 MUg g(-1) (P<0.001) in experimentally induced arterial thrombi
      in mice while increasing blood loss at 1 MUg g(-1) (P<0.01). CONCLUSIONS:
      Diannexin binds to PS with high affinity and is a potent inhibitor of platelet
      mediated events during thrombus formation.

PMID- 22463103
TI  - Solid-state charge-based device for control of catalytic carbon monoxide
      oxidation on platinum nanofilms using external bias and light.
AB  - Using a Pt/Si catalytic nanodiode, we externally control the rate of CO oxidation
      on a Pt nanofilm. The catalytic reaction can be turned on and off by alternating
      between bias states of the device. Additionally, the reaction rate is sensitive
      to photocurrent induced by visible light. The effects of both bias and light show
      that negative charge on the Pt increases catalytic activity, while positive
      charge on the Pt decreases catalytic activity for CO oxidation.

PMID- 22463104
TI  - Tailor-made quantum dot and iron oxide based contrast agents for in vitro and in
      vivo tumor imaging.
AB  - The biofunctionalization of CdSe/CdS/ZnS quantum dots and Fe(3)O(4) nanocrystals
      using a novel ligand system based on polyisoprene-block-poly(ethylene oxide)
      ligands is described. The synthesis includes a partial ligand exchange of the
      hydrophobic nanocrystals with amino-functionalized polyisoprene ligands, followed
      by seeded micelle formation of the diblock-copolymers in water. The resulting
      water-soluble quantum dots showed fluorescence quantum efficiencies in the 40 to
      50% range and extraordinary fluorescence stability in the biological environment
      after cross-linking of the polyisoprene moiety of the ligand shell. No toxicity
      was detected by water-soluble tetrazolium (WST8) and lactate dehydrogenase (LDH)
      assays, even at very high nanoparticle concentrations, and almost no nonspecific
      cell adhesion was detected. The ligand shell was further coupled to the antigen
      related cell adhesion molecule (CEACAM) specific monoclonal antibody T84.1. The
      so-conjugated Fe(3)O(4) nanocrystals allowed in vitro and in vivo tumor targeting
      by magnetic resonance imaging.

PMID- 22463106
TI  - Olefin complexes of divalent ruthenium formed by chelating olefinic tertiary
      phosphines and arsines.

PMID- 22463105
TI  - Long-term follow-up of renal function in dogs after treatment for ACTH-dependent
      hyperadrenocorticism.
AB  - BACKGROUND: Systemic hypertension and proteinuria are frequent complications in
      dogs with Cushing's syndrome and do not always resolve after treatment of
      hypercortisolism. Therefore, dogs with Cushing's syndrome may be at risk for
      renal dysfunction before and after treatment. HYPOTHESIS/OBJECTIVES: To assess
      renal function in dogs with ACTH-dependent hyperadrenocorticism (ADHAC) before
      and after treatment. ANIMALS: A total of 19 dogs with ADHAC and 12 control dogs.
      METHODS: Renal function was assessed before and at 1, 3, 6, and 12 months after
      treatment. Twelve dogs were treated with trilostane and 7 dogs by transsphenoidal
      hypophysectomy. Routine renal markers were measured and urinary albumin (uALB),
      immunoglobulin G (uIgG), and retinol-binding protein (uRBP) were assessed by
      ELISA. Urinary N-acetyl-beta-D-glucosaminidase (uNAG) was determined
      colorimetrically. All urinary markers were indexed to urinary creatinine
      concentration (c). Plasma clearance of creatinine (Cl(creat)), exo-iohexol
      (Cl(exo)), and endo-iohexol (Cl(endo)) was used to measure glomerular filtration
      rate (GFR). Data were analyzed using a general linear model. RESULTS: Serum
      creatinine and urea concentrations increased post-treatment, but remained within
      reference ranges. Plasma Cl(creat) and Cl(endo) were significantly lower post
      treatment, whereas Cl(exo) was not different. Urinary protein-to-creatinine ratio
      (UPC), uALB/c, uIgG/c, and uRBP/c were decreased post-treatment, but at 12 months
      5/13 dogs remained proteinuric. Urinary NAG/c did not change significantly.
      CONCLUSIONS AND CLINICAL IMPORTANCE: A decrease in GFR and persistent proteinuria
      post-treatment may warrant the clinician's attention. Future research including
      renal histopathology of dogs with persistent proteinuria or low GFR is needed to
      further assess renal outcome.

PMID- 22463108
TI  - Arthroscopic approach and intraarticular anatomy of the stifle in South American
      camelids.
AB  - OBJECTIVE: To describe a cranial arthroscopic approach to the stifle of South
      American camelids and to report our clinical experience with camelid stifle
      arthroscopy. STUDY DESIGN: Experimental study and retrospective case series.
      ANIMALS: (1) Cadaveric alpaca hindlimbs (n = 18; 9 alpacas); (2) 1 alpaca and 1
      llama METHODS: Polymethylmethacrylate joint casts (n = 2) were made to define
      stifle joint dimensions. Cadaveric stifle joints (n = 16) were evaluated
      arthroscopically to determine arthroscopic portal locations, describe the
      intraarticular anatomy, and report potential complications. An alpaca and a llama
      with stifle joint disease had diagnostic arthroscopy. RESULTS: Successful entry
      into the stifle joint was achieved in 16 cadaver limbs. Observed structures were:
      the suprapatellar pouch, articular surface of the patella, femoral trochlear
      ridges and groove, cranial aspect of the femoral condyles (n = 16); distal aspect
      of the cranial and proximal aspect of the caudal cruciate ligaments (14); and
      cranial aspects of the medial and lateral menisci (11), and cranial meniscotibial
      and intermeniscal ligaments (8). Stifle arthroscopy allowed for joint evaluation
      and removal of osteochondral fragments in 1 alpaca and 1 llama with naturally
      occurring stifle disease. Complications of cadaver or live procedures included
      minor cartilage scoring (3 stifles) and subcutaneous periarticular fluid
      accumulation (8 stifles). CONCLUSIONS: Arthroscopy provides a safe approach for
      diagnosis and treatment of stifle lesions in South American camelids.

PMID- 22463107
TI  - Trends in oral drug bioavailability following bariatric surgery: examining the
      variable extent of impact on exposure of different drug classes.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Changes to oral drug bioavailability
      have been observed post bariatric surgery. However, the magnitude and the
      direction of changes have not been assessed systematically to provide insights
      into the parameters governing the observed trends. Understanding these can help
      with dose adjustments. WHAT THIS STUDY ADDS: Analysis of drug characteristics
      based on a biopharmaceutical classification system is not adequate to explain
      observed trends in altered oral drug bioavailability following bariatric surgery,
      although the findings suggest solubility to play an important role. AIMS: To
      identify the most commonly prescribed drugs in a bariatric surgery population and
      to assess existing evidence regarding trends in oral drug bioavailability post
      bariatric surgery. METHODS: A retrospective audit was undertaken to document
      commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS
      hospital in the UK and to assess practice for drug administration following
      bariatric surgery. The available literature was examined for trends relating to
      drug permeability and solubility with regards to the Biopharmaceutics
      Classification System (BCS) and main route of elimination. RESULTS: No
      significant difference in the 'post/pre surgery oral drug exposure ratio' (ppR)
      was apparent between BCS class I to IV drugs, with regards to dose number (Do) or
      main route of elimination. Drugs classified as 'solubility limited' displayed an
      overall reduction as compared with 'freely soluble' compounds, as well as an
      unaltered and increased ppR. CONCLUSION: Clinical studies establishing guidelines
      for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow
      therapeutic window or without a readily assessed clinical endpoint, are
      warranted. Using mechanistically based pharmacokinetic modelling for simulating
      the multivariate nature of changes in drug exposure may serve as a useful tool in
      the further understanding of postoperative trends in oral drug exposure and in
      developing practical clinical guidance.

PMID- 22463110
TI  - Multilocus sequence typing reveals high genetic diversity and epidemic population
      structure for the fish pathogen Yersinia ruckeri.
AB  - Yersinia ruckeri is the causative agent of enteric redmouth in fish and one of
      the major bacterial pathogens causing losses in salmonid aquaculture. Previously
      typing methods, including restriction enzyme analysis, pulsed-field gel
      electrophoresis and multilocus enzyme electrophoresis (MLEE) have indicated a
      clonal population structure. In this work, we describe a multilocus sequence
      typing (MLST) scheme for Y.ruckeri based on the internal fragment sequence of six
      housekeeping genes. This MLST scheme was applied to 103 Y.ruckeri strains from
      diverse geographic areas and hosts as well as environmental sources. Sequences
      obtained from this work were deposited and are available in a public database
      (http://publmst.org/yruckeri/). Thirty different sequence types (ST) were
      identified, 21 of which were represented by a single isolate, evidencing high
      genetic diversity. ST2 comprised more than one-third of the isolates and was most
      frequently observed among isolates from trout. Two major clonal complexes (CC)
      were identified by eBURST analysis showing a common evolutionary origin for 94
      isolates forming 21 STs into CC1 and for 6 isolates of 6 STs in the CC2. It was
      also possible to associate some unique ST with isolates from recent outbreaks in
      vaccinated salmonid fish.

PMID- 22463109
TI  - Combinatorial stresses kill pathogenic Candida species.
AB  - Pathogenic microbes exist in dynamic niches and have evolved robust adaptive
      responses to promote survival in their hosts. The major fungal pathogens of
      humans, Candida albicans and Candida glabrata, are exposed to a range of
      environmental stresses in their hosts including osmotic, oxidative and
      nitrosative stresses. Significant efforts have been devoted to the
      characterization of the adaptive responses to each of these stresses. In the
      wild, cells are frequently exposed simultaneously to combinations of these
      stresses and yet the effects of such combinatorial stresses have not been
      explored. We have developed a common experimental platform to facilitate the
      comparison of combinatorial stress responses in C. glabrata and C. albicans. This
      platform is based on the growth of cells in buffered rich medium at 30 degrees C,
      and was used to define relatively low, medium and high doses of osmotic (NaCl),
      oxidative (H(2)O(2)) and nitrosative stresses (e.g., dipropylenetriamine (DPTA)
      NONOate). The effects of combinatorial stresses were compared with the
      corresponding individual stresses under these growth conditions. We show for the
      first time that certain combinations of combinatorial stress are especially
      potent in terms of their ability to kill C. albicans and C. glabrata and/or
      inhibit their growth. This was the case for combinations of osmotic plus
      oxidative stress and for oxidative plus nitrosative stress. We predict that
      combinatorial stresses may be highly significant in host defences against these
      pathogenic yeasts.

PMID- 22463111
TI  - Controversies in the neurosurgical management of cerebellar hemorrhage and
      infarction.
AB  - Evidence-based guidelines for the management of hemorrhagic and ischemic
      cerebellar stroke are sparse, and most available data come from Class III
      studies. As a result, opinions and practices regarding the nature and role of
      neurosurgical intervention vary widely. A comprehensive literature review was
      conducted to adjudicate several contentious issues, such as the difference in the
      management of cerebellar hemorrhage versus infarction, criteria for imaging to
      exclude an underlying structural lesion, the value of MRI for patient selection,
      the role of external ventricular drainage, the indications for operative
      management, the timing of surgical intervention, and various options of surgical
      technique, among others. Treatment algorithms proposed in several different
      studies are compared and contrasted. This analysis is concluded by a summary of
      the recommendations from the American Stroke Association, which advises that
      patients with cerebellar hemorrhage who experience neurological deterioration or
      who have brainstem compression and/or hydrocephalus due to ventricular
      obstruction should undergo surgical evacuation of the hemorrhage as soon as
      possible, and that initial treatment of such patients with ventricular drainage
      alone rather than surgical removal of the hemorrhage is not recommended.

PMID- 22463112
TI  - Intracerebral hemorrhage secondary to intravenous and endovascular intraarterial
      revascularization therapies in acute ischemic stroke: an update on risk factors,
      predictors, and management.
AB  - Intracerebral hemorrhage (ICH) secondary to intravenous and intraarterial
      revascularization strategies for emergent treatment of acute ischemic stroke is
      associated with high mortality. ICH from systemic thrombolysis typically occurs
      within the first 24-36 hours of treatment initiation and is characterized by
      rapid hematoma development and growth. Pathophysiological mechanisms of
      revascularization therapy-induced ICH are complex and involve a combination of
      several distinct processes, including the direct effect of thrombolytic agents,
      disruption of the blood-brain barrier secondary to ischemia, and direct vessel
      damage from wire and microcatheter manipulations during endovascular procedures.
      Several definitions of ICH secondary to thrombolysis currently exist, depending
      on clinical or radiological characteristics used. Multiple studies have
      investigated clinical and laboratory risk factors associated with higher rates of
      ICH in this setting. Early ischemic changes seen on noncontrast CT scanning are
      strongly associated with higher rates of hemorrhage. Modern imaging techniques,
      particularly CT perfusion, provide rapid assessment of hemodynamic parameters of
      the brain. Specific patterns of CT perfusion maps can help identify patients who
      are likely to benefit from revascularization or to develop hemorrhagic
      complications. There are no established guidelines that describe management of
      revascularization therapy-induced ICH, and great variability in treatment
      protocols currently exist. General principles that apply to the management of
      spontaneous ICH might not be as effective for revascularization therapy-induced
      ICH. In this article, the authors review current knowledge of risk factors and
      radiological predictors of ICH secondary to stroke revascularization techniques
      and analyze medical and surgical management strategies for ICH in this setting.

PMID- 22463113
TI  - Minimally invasive treatment for intracerebral hemorrhage.
AB  - Spontaneous intracerebral hemorrhage is a serious public health problem and is
      fatal in 30%-50% of all occurrences. The role of open surgical management of
      supratentorial intracerebral hemorrhage is still unresolved. A recent consensus
      conference sponsored by the National Institutes of Health suggests that minimally
      invasive techniques to evacuate clots appear to be a promising area and warrant
      further investigation. In this paper the authors review past, current, and
      potential future methods of treating intraparenchymal hemorrhages with minimally
      invasive techniques and review new data regarding the role of stereotactically
      placed catheters and thrombolytics.

PMID- 22463114
TI  - External ventricular drainage alone versus endoscopic surgery for severe
      intraventricular hemorrhage: a comparative retrospective analysis on outcome and
      shunt dependency.
AB  - OBJECT: Massive intraventricular hemorrhages (IVHs) require aggressive and rapid
      management to decrease intracranial hypertension, because the amount of
      intraventricular blood is a strong negative prognostic predictor on outcome.
      Neuroendoscopy may offer some advantages over more traditional surgical
      approaches on outcome and may decrease the number of shunt procedures that need
      to be performed. METHODS: The authors retrospectively reviewed the clinical and
      radiological data in 96 patients treated for massive IVH who were admitted
      between January 1996 and June 2008 to the neurosurgery unit after undergoing
      emergency CT scanning. Forty-eight patients (Group A) were treated with
      endoscopic aspiration surgery using a flexible endoscope with a "freehand"
      technique. A historical group of 48 patients (Group B) treated using external
      ventricular drain (EVD) placement alone was used as a comparison. The authors
      compared the radiological results with the clinical outcomes at 1 year according
      to the modified Rankin Scale and the need for internal CSF shunt treatment in the
      2 groups. RESULTS: Endoscopic aspiration did not significantly affect the outcome
      at 1 year as determined using the modified Rankin Scale. Patients who underwent
      endoscopy had an EVD in place for 0.18 days fewer than patients treated with an
      EVD alone. Patients undergoing external ventricular drainage alone had a 5 times
      greater chance of requiring a shunting procedure than those treated using
      neuroendoscopy and external ventricular drainage. Neuroendoscopy plus external
      drainage reduces shunting rates by 34% when compared with external drainage
      alone. CONCLUSIONS: The reduction in internal shunt surgery encourages the
      adoption of neuroendoscopic aspiration of severe IVH as a therapeutic tool to
      decrease shunt dependency.

PMID- 22463115
TI  - Predictors of long-term shunt-dependent hydrocephalus in patients with
      intracerebral hemorrhage requiring emergency cerebrospinal fluid diversion.
AB  - OBJECT: Intracerebral hemorrhage (ICH) is frequently complicated by acute
      hydrocephalus, necessitating emergency CSF diversion with a subset of patients,
      ultimately requiring long-term treatment via placement of permanent ventricular
      shunts. It is unclear what factors may predict the need for ventricular shunt
      placement in this patient population. METHODS: The authors performed a
      retrospective analysis of a prospective database (ICH Outcomes Project)
      containing patients with nontraumatic ICH admitted to the neurological ICU at
      Columbia University Medical Center between January 2009 and September 2011. A
      multiple logistic regression model was developed to identify independent
      predictors of shunt-dependent hydrocephalus after ICH. The following variables
      were included: patient age, admission Glasgow Coma Scale score, temporal horn
      diameter on admission CT imaging, bicaudate index, admission ICH volume and
      location, intraventricular hemorrhage volume, Graeb score, LeRoux score, third or
      fourth ventricle hemorrhage, and intracranial pressure (ICP) and ventriculitis
      during hospital stay. RESULTS: Of 210 patients prospectively enrolled in the ICH
      Outcomes Project, 64 required emergency CSF diversion via placement of an
      external ventricular drain and were included in the final cohort. Thirteen of
      these patients underwent permanent ventricular CSF shunting prior to discharge.
      In univariate analysis, only thalamic hemorrhage and elevated ICP were
      significantly associated with the requirement for permanent CSF diversion, with p
      values of 0.008 and 0.033, respectively. Each remained significant in a multiple
      logistic regression model in which both variables were present. CONCLUSIONS: Of
      patients with ICH requiring emergency CSF diversion, those with persistently
      elevated ICP and thalamic location of their hemorrhage are at increased odds of
      developing persistent hydrocephalus, necessitating permanent ventricular shunt
      placement. These factors may assist in predicting which patients will require
      permanent CSF diversion and could ultimately lead to improvements in the
      management of this disorder and the outcome in patients with ICH.

PMID- 22463116
TI  - Telemedicine-assisted treatment of patients with intracerebral hemorrhage.
AB  - OBJECT: Telemedicine provides a new approach to improve stroke care in community
      settings, delivering acute stroke expertise to hospitals in rural areas. Given
      the controversies in many aspects of the treatment of intracerebral hemorrhage
      (ICH) and the lack of guidelines, a prompt neurosurgical second opinion may
      facilitate the treatment of patients with ICH. Here, the authors' 8-year
      experience with the use of telemedicine in the management of ICH is reported.
      METHODS: The medical records of patients with ICH treated through a telemedicine
      system in the district of Messina, Italy, between June 2003 and June 2011 were
      retrospectively reviewed. Neuroradiological and clinical data for patients were
      transmitted through a high-technology "hub-and-spoke" telemedicine network.
      Neurosurgical teleconsulting (at the hub) was available for 7 peripheral
      hospitals (spokes) serving about 700,000 people. The authors analyzed 1) the time
      between peripheral hospital admission and the specialized second opinion
      consultation, 2) primary and secondary transfers to the authors' neurosurgery
      department, and 3) the treatments (surgical or medical) of patients transferred
      to the hub. RESULTS: The telemedicine network was used to treat more than 2800
      patients, 733 with ICH. A neurosurgical consultation was provided in 38 minutes
      versus 160 minutes for a consultation without telemedicine. One hundred seventy
      six (24%) of 733 patients were primarily transferred to the hub. Ninety-five
      patients (13%) underwent surgical treatment. The remaining 81 patients (11%)
      underwent neurointensive care. Eight (1.4%) of 557 patients treated at the spokes
      needed a secondary transfer for surgical treatment because of a worsening
      clinical condition and/or CT findings. Considering secondary and inappropriate
      transfers, the interpretation of data was correct in 96.5% of cases. CONCLUSIONS:
      Telemedicine allowed rapid visualization of neuroradiological and clinical data,
      providing neurosurgical expertise to community hospitals on demand and within
      minutes. It allowed the treatment of patients at peripheral hospitals and
      optimized resources. A small percentage of patients treated at the peripheral
      hospitals had secondary deterioration. Telemedicine allowed fast patient transfer
      when necessary and provided improved accuracy in patient care.

PMID- 22463117
TI  - Cerebral amyloid angiopathy-associated intracerebral hemorrhage: pathology and
      management.
AB  - Amyloid angiopathy-associated intracerebral hemorrhage (ICH) comprises 12%-15% of
      lobar ICH in the elderly. This growing population has an increasing incidence of
      thrombolysis-related hemorrhages, causing the management of hemorrhages
      associated with cerebral amyloid angiopathy (CAA) to take center stage. A concise
      reference assimilating the pathology and management of this clinical entity does
      not exist. Amyloid angiopathy-associated hemorrhages are most often solitary, but
      the natural history often progresses to include multifocal and recurrent
      hemorrhages. Compared with other causes of ICH, patients with CAA-associated
      hemorrhages have a lower mortality rate but an increased risk of recurrence.
      Unlike hypertensive arteriolar hemorrhages that occur in penetrating subcortical
      vessels, CAA-associated hemorrhages are superficial in location due to
      preferential involvement of vessels in the cerebral cortex and meninges. This
      feature makes CAA-associated hemorrhages easier to access surgically. In this
      paper, the authors discuss 3 postulates regarding the pathogenesis of amyloid
      hemorrhages, as well as the established clinicopathological classification of
      amyloid angiopathy and CAA-associated ICH. Common inheritance patterns of
      familial CAA with hemorrhagic strokes are discussed along with the role of
      genetic screening in relatives of patients with CAA. The radiological
      characteristics of CAA are described with specific attention to CAA-associated
      microhemorrhages. The detection of these microhemorrhages may have important
      clinical implications on the administration of anticoagulation and antiplatelet
      therapy in patients with probable CAA. Poor patient outcome in CAA-associated ICH
      is associated with dementia, increasing age, hematoma volume and location,
      initial Glasgow Coma Scale score, and intraventricular extension. The surgical
      management strategies for amyloid hemorrhages are discussed with a review of
      published surgical case series and their outcomes with a special attention to
      postoperative hemorrhage.

PMID- 22463118
TI  - Thrombin and hemin as central factors in the mechanisms of intracerebral
      hemorrhage-induced secondary brain injury and as potential targets for
      intervention.
AB  - Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant
      morbidity and mortality. Brain injury due to ICH initially occurs within the
      first few hours as a result of mass effect due to hematoma formation. However,
      there is increasing interest in the mechanisms of secondary brain injury as many
      patients continue to deteriorate clinically despite no signs of rehemorrhage or
      hematoma expansion. This continued insult after primary hemorrhage is believed to
      be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of
      intraparenchymal blood. The main factors responsible for this injury are thrombin
      and erythrocyte contents such as hemoglobin. Therapies including thrombin
      inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and
      antiinflammatory drugs are currently under investigation for reducing this
      secondary brain injury. This review will discuss the molecular mechanisms of
      brain injury as a result of intraparenchymal blood, potential targets for
      therapeutic intervention, and treatment strategies currently in development.

PMID- 22463119
TI  - Tarlov cysts.

PMID- 22463120
TI  - Intracerebral hemorrhage.

PMID- 22463121
TI  - Effect of training on exposure judgment accuracy of industrial hygienists.
AB  - Results are presented from a study that investigated the effect of data
      interpretation training on exposure judgment accuracy of industrial hygienists
      across several companies in different industry sectors. Participating companies
      provided monitoring information on specific exposure tasks. Forty-nine hygienists
      from six companies participated in the study, and 22 industrial tasks were
      evaluated. The number of monitoring data points for individual tasks varied
      between 5 and 24. After reviewing all available basic characterization
      information for the job, task, and chemical, hygienists were asked to provide
      their judgment on the probability of the 95th percentile of the underlying
      exposure distribution being located in one of four exposure categories relative
      to the occupational exposure limit as outlined in the AIHA exposure assessment
      strategy. Ninety-three qualitative judgments (i.e., without reviewing monitoring
      data) and 2142 quantitative judgments (i.e., those made after reviewing
      monitoring data) were obtained. Data interpretation training, with simple rules
      of thumb for estimating 95th percentiles, was provided to all hygienists. A data
      interpretation test was administered before and after training. All exposure task
      judgments were collected before and after training. Data interpretation test
      accuracy for the hygienists increased from 48% to 67% after training (p < 0.001)
      and a significant underestimation bias was removed. Hygienist quantitative task
      judgment accuracy improved from 46% to 69% (p < 0.001) post-training. Accuracy
      results showed good improvement in industrial hygienists' quantitative judgments
      as a result of training. Hence, the use of statistical tools is promoted to
      improve judgments based on monitoring data and provide feedback and calibration
      to improve qualitative judgments. It may be worthwhile to develop standard
      training programs to improve exposure judgments.

PMID- 22463122
TI  - Trade-offs in disinfection byproduct formation associated with precursor
      preoxidation for control of N-nitrosodimethylamine formation.
AB  - Chloramines in drinking water may form N-nitrosodimethylamine (NDMA). Various
      primary disinfectants can deactivate NDMA precursors prior to chloramination.
      However, they promote the formation of other byproducts. This study compared the
      reduction in NDMA formation due to chlorine, ozone, chlorine dioxide, and UV over
      oxidant exposures relevant to Giardia control coupled with postchloramination
      under conditions relevant to drinking water practice. Ten waters impacted by
      treated wastewater, poly(diallyldimethylammonium chloride) (polyDADMAC) polymer,
      or anion exchange resin were examined. Ozone reduced NDMA formation by 50% at
      exposures as low as 0.4 mg*min/L. A similar reduction in NDMA formation by
      chlorination required ~60 mg*min/L exposure. However, for some waters,
      chlorination actually increased NDMA formation at lower exposures. Chlorine
      dioxide typically had limited efficacy regarding NDMA precursor destruction;
      moreover, it increased NDMA formation in some cases. UV decreased NDMA formation
      by ~30% at fluences >500 mJ/cm(2), levels relevant to advanced oxidation. For the
      selected pretreatment oxidant exposures, concentrations of regulated
      trihalomethanes, haloacetic acids, bromate, and chlorite typically remained below
      current regulatory levels. Chloropicrin and trichloroacetaldehyde formation were
      increased by preozonation or medium pressure UV followed by postchloramination.
      Among preoxidants, ozone achieved the greatest reduction in NDMA formation at the
      lowest oxidant exposure associated with each disinfectant. Accordingly,
      preozonation may inhibit NDMA formation with minimal risk of promotion of other
      byproducts. Bromide >500 MUg/L generally increased NDMA formation during
      chloramination. Higher temperatures increased NDMA precursor destruction by
      preoxidants but also increased NDMA formation during postchloramination. The net
      effect of these opposing trends on NDMA formation was water-specific.

PMID- 22463123
TI  - Computational models for in-vitro anti-tubercular activity of molecules based on
      high-throughput chemical biology screening datasets.
AB  - BACKGROUND: The emergence of Multi-drug resistant tuberculosis in pandemic
      proportions throughout the world and the paucity of novel therapeutics for
      tuberculosis have re-iterated the need to accelerate the discovery of novel
      molecules with anti-tubercular activity. Though high-throughput screens for anti
      tubercular activity are available, they are expensive, tedious and time-consuming
      to be performed on large scales. Thus, there remains an unmet need to prioritize
      the molecules that are taken up for biological screens to save on cost and time.
      Computational methods including Machine Learning have been widely employed to
      build classifiers for high-throughput virtual screens to prioritize molecules for
      further analysis. The availability of datasets based on high-throughput
      biological screens or assays in public domain makes computational methods a
      plausible proposition for building predictive models. In addition, this approach
      would save significantly on the cost, effort and time required to run high
      throughput screens. RESULTS: We show that by using four supervised state-of-the
      art classifiers (SMO, Random Forest, Naive Bayes and J48) we are able to generate
      in-silico predictive models on an extremely imbalanced (minority class ratio:
      0.6%) large dataset of anti-tubercular molecules with reasonable AROC (0.6-0.75)
      and BCR (60-66%) values. Moreover, these models are able to provide 3-4 fold
      enrichment over random selection. CONCLUSIONS: In the present study, we have used
      the data from in-vitro screens for anti-tubercular activity from a high
      throughput screen available in public domain to build highly accurate classifiers
      based on molecular descriptors of the molecules. We show that Machine Learning
      tools can be used to build highly effective predictive models for virtual high
      throughput screens to prioritize molecules from large molecular libraries.

PMID- 22463124
TI  - Non-suicidal self-injury (Nssi) in adolescent inpatients: assessing personality
      features and attitude toward death.
AB  - BACKGROUND: Non-suicidal self-injury (NSSI) is a common concern among
      hospitalized adolescents, and can have significant implications for short and
      long-term prognosis. Little research has been devoted on how personality features
      in severely ill adolescents interact with NSSI and "attitude toward life and
      death" as a dimension of suicidality. Developing more specific assessment
      methodologies for adolescents who engage in self-harm without suicidal intent is
      relevant given the recent proposal of a non-suicidal self-injury (NSSI) disorder
      and may be useful in predicting risk in psychiatrically impaired subjects.
      METHODS: Consecutively hospitalized adolescents in a psychiatric unit (N = 52;
      71% females; age 12-19 years), reporting at least one recent episode of self-harm
      according to the Deliberate Self-harm Inventory, were administered the Structured
      Clinical Interview for DSM Mental Disorders and Personality Disorders (SCID I and
      II), the Children's Depression Inventory and the Multi-Attitude Suicide Tendency
      Scale (MAST). RESULTS: Mean age onset of NSSI in the sample was 12.3 years. All
      patients showed "repetitive" NSSI (high frequency of self-harm), covering
      different modalities. Results revealed that 63.5% of adolescents met criteria for
      Borderline Personality Disorder (BPD) and that the rest of the sample also met
      criteria for personality disorders with dysregulated traits. History of suicide
      attempts was present in 46.1% of cases. Elevated depressive traits were found in
      53.8%. Results show a statistically significant negative correlation between the
      score on the "Attraction to Life" subscale of the MAST and the frequency and
      diversification of self-harming behaviors. CONCLUSIONS: Most adolescent
      inpatients with NSSI met criteria for emotionally dysregulated personality
      disorders, and showed a reduced "attraction to life" disposition and significant
      depressive symptoms. This peculiar psychopathological configuration must be
      addressed in the treatment of adolescent inpatients engaging in NSSI and taken
      into account for the prevention of suicidal behavior in self-injuring adolescents
      who do not exhibit an explicit intent to die.

PMID- 22463126
TI  - Relationship between the elevated mean platelet volume and coronary microvascular
      function in patients with idiopathic dilated cardiomyopathy.

PMID- 22463125
TI  - Rationale, design, methodology and sample characteristics for the family partners
      for health study: a cluster randomized controlled study.
AB  - BACKGROUND: Young children who are overweight are at increased risk of becoming
      obese and developing type 2 diabetes and cardiovascular disease later in life.
      Therefore, early intervention is critical. This paper describes the rationale,
      design, methodology, and sample characteristics of a 5-year cluster randomized
      controlled trial being conducted in eight elementary schools in rural North
      Carolina, United States. METHODS/DESIGN: The first aim of the trial is to examine
      the effects of a two-phased intervention on weight status, adiposity, nutrition
      and exercise health behaviors, and self-efficacy in overweight or obese 2nd, 3
      rd, and 4th grade children and their overweight or obese parents. The primary
      outcome in children is stabilization of BMI percentile trajectory from baseline
      to 18 months. The primary outcome in parents is a decrease in BMI from baseline
      to 18 months. Secondary outcomes for both children and parents include adiposity,
      nutrition and exercise health behaviors, and self-efficacy from baseline to 18
      months. A secondary aim of the trial is to examine in the experimental group, the
      relationships between parents and children's changes in weight status, adiposity,
      nutrition and exercise health behaviors, and self-efficacy. An exploratory aim is
      to determine whether African American, Hispanic, and non-Hispanic white children
      and parents in the experimental group benefit differently from the intervention
      in weight status, adiposity, health behaviors, and self-efficacy.A total of 358
      African American, non-Hispanic white, and bilingual Hispanic children with a BMI
      >= 85th percentile and 358 parents with a BMI >= 25 kg/m2 have been inducted over
      3 1/2 years and randomized by cohort to either an experimental or a wait-listed
      control group. The experimental group receives a 12-week intensive intervention
      of nutrition and exercise education, coping skills training and exercise (Phase
      I), 9 months of continued monthly contact (Phase II) and then 6 months (follow
      up) on their own. Safety endpoints include adverse event reporting. Intention-to
      treat analysis will be applied to all data. DISCUSSION: Findings from this trial
      may lead to an effective intervention to assist children and parents to work
      together to improve nutrition and exercise patterns by making small lifestyle
      pattern changes. TRIAL REGISTRATION: NCT01378806.

PMID- 22463127
TI  - Concise synthesis of 2-benzazepine derivatives and their biological activity.
AB  - 2-Benzazepines, which are potentially good candidates for new drug therapies to
      treat skin wounds, were readily prepared from substituted cinnamylamide via an
      intramolecular Friedel-Crafts reaction. With few steps and effective reactions,
      the procedure enables a rapid derivatization of 2-benzazepines. Moreover,
      optically active 4-substituted-2-benzazepines were prepared from chiral alpha
      substituted cinnamylamides, which were readily prepared by asymmetric alpha
      alkylation of chiral cinnamyl oxazolidinone amides. We have easily prepared a
      library of more than 20 derivatives and examined the biological activity of the
      compounds.

PMID- 22463128
TI  - Pivotal roles of shear stress in the microenvironmental changes that occur within
      sentinel lymph nodes.
AB  - A sentinel lymph node (SLN) is the first lymph node that receives drainage from a
      primary tumor. According to their physiological and biomechanical
      characteristics, we hypothesized that SLN contains lymphatic endothelial cells
      (LEC) that are constantly loaded with high levels of shear stress, which might
      contribute to the production of a suitable environment for micrometastasis within
      them. To test this hypothesis, we investigated the effects of shear stress
      stimulation on the expression of adhesion molecules on human LEC isolated from
      the lymph vessels nearest the SLN of breast cancers, and on the release of ATP
      from human LEC. The study clarified that the shear stress stimulation produced a
      significant increase of ICAM-1 expression at protein and mRNA levels in human
      LEC. Next, we examined whether the shear stress-mediated increase of ICAM-1
      expression accelerates the attachment of carcinoma cells to human LEC. Finally,
      in in vivo experiments, we evaluated whether exogenous ATP facilitates the
      expression of carcinoma cell-ligated adhesion molecules in rat SLN. In
      conclusion, shear stress stimulation induces ICAM-1 expression on human LEC by
      activating cell surface F(1) /F(O) ATP synthase, which might contribute to the
      development of a premetastatic environment within SLN.

PMID- 22463129
TI  - Heated distributed temperature sensing for field scale soil moisture monitoring.
AB  - Characterizing both spatial and temporal soil moisture (theta) dynamics at site
      scales is difficult with existing technologies. To address this shortcoming, we
      developed a distributed soil moisture sensing system that employs a distributed
      temperature sensing system to monitor thermal response at 2 m intervals along the
      length of a buried cable which is subjected to heat pulses. The cable temperature
      response to heating, which is strongly dependent on soil moisture, was
      empirically related to colocated, dielectric-based theta measurements at three
      locations. Spatially distributed, and temporally continuous estimates of theta
      were obtained in dry conditions (theta<= 0.31) using this technology (root mean
      square error [RMSE] = 0.016), but insensitivity of the instrument response curve
      adversely affected accuracy under wet conditions (RMSE = 0.050).

PMID- 22463130
TI  - Electromyographic evaluation of masseter muscle activity in horses fed (i)
      different types of roughage and (ii) maize after different hay allocations.
AB  - The aims of this study were to monitor electromyographic (EMG) activity of
      masseter muscle in healthy horses fed (i) different types of roughage and (ii)
      maize after different hay allocations. Four horses were offered the following
      three diets ad libitum: hay, haylage or straw/alfalfa chaff (SAC). In a second
      trial, four horses were fed cracked maize (CM) and hay in three different orders:
      (i) CM after a 12-h overnight fast; (ii) CM immediately after restricted hay
      intake (0.6 kg hay/100 kg BW); or 3) CM after hay intake ad libitum. The activity
      of the masseter muscle was determined by EMG (IED((r)) ), and the following were
      measured: amplitude (muscle action potential = MAP, maximum voltage) and duration
      of MAP (s). The intake of hay or haylage was associated with intense masseter
      muscle activity (MAP: hay, 10 +/- 1.7 V; haylage, 11 +/- 3.3 V; and duration of
      MAP: hay, 0.31 +/- 0.04 s; haylage, 0.30 +/- 0.04 s). Similar intense chewing was
      measured for SAC (MAP 13 +/- 3.8 V), although duration of the chewing cycle was
      relatively short (0.22 +/- 0.03 s, diet p < 0.05), which is possibly related to
      the shorter fibre length. CM was consumed rapidly, with less intense masseter
      muscle activity (MAP 6.0 +/- 1.5 V). Hay intake before CM did not affect chewing
      force of CM, but duration of chewing cycle was significantly prolonged by feeding
      hay ad libitum before CM was fed. The consumption of hay, haylage or SAC was
      associated with intensive masseter muscle activity that was likely to stimulate
      salivary flow rate. In contrast to roughage, concentrates like CM are consumed
      rapidly with less intensive masseter muscle activity. This situation is
      associated with a low salivary flow that may have an adverse effect on gastric
      function.

PMID- 22463131
TI  - Blood biomarkers in stroke: research and clinical practice.
AB  - Blood biomarkers may have applications in stroke diagnosis, outcome prediction,
      or treatment. In this article, we provide a focused review on some of the
      methodological challenges and potential developments of biomarkers in stroke. We
      review the approaches to the development of a diagnostic blood marker: a
      candidate marker approach, marker panels, and -omics. Then we examined the role
      of blood markers to predict recurrent stroke and treatment response in stroke.

PMID- 22463132
TI  - Technologies and combination therapies for enhancing movement training for people
      with a disability.
AB  - There has been a dramatic increase over the last decade in research on
      technologies for enhancing movement training and exercise for people with a
      disability. This paper reviews some of the recent developments in this area,
      using examples from a National Science Foundation initiated study of mobility
      research projects in Europe to illustrate important themes and key directions for
      future research. This paper also reviews several recent studies aimed at
      combining movement training with plasticity or regeneration therapies, again
      drawing in part from European research examples. Such combination therapies will
      likely involve complex interactions with motor training that must be understood
      in order to achieve the goal of eliminating severe motor impairment.

PMID- 22463133
TI  - Heavily male-biased long-distance dispersal of orang-utans (genus: Pongo), as
      revealed by Y-chromosomal and mitochondrial genetic markers.
AB  - Mating systems are thought to be an important determinant of dispersal strategies
      in most animals, including the great apes. As the most basal taxon of all great
      apes, orang-utans can provide information about the evolution of mating systems
      and their consequences for population structure in this Family. To assess the sex
      specific population structure in orang-utans, we used a combination of paternally
      transmitted Y-chromosomal genetic markers and maternally transmitted
      mitochondrial DNA sequences. Markers transmitted through the more philopatric sex
      are expected to show stronger differentiation among populations than the ones
      transmitted through the dispersing sex. We studied these patterns using 70
      genetic samples from wild orang-utans from seven Bornean and two Sumatran
      populations. We found pronounced population structure in haplotype networks of
      mitochondrial sequence data, but much less so for male-specific markers.
      Similarly, mitochondrial genetic differentiation was twice as high among
      populations compared to Y-chromosomal variation. We also found that genetic
      distance increased faster with geographic distance for mitochondrial than for Y
      linked markers, leading to estimates of male dispersal distances that are several
      fold higher than those of females. These findings provide evidence for strong
      male-biased dispersal in orang-utans. The transition to predominantly female
      biased dispersal in the great ape lineage appears to be correlated with life in
      multimale groups and may reflect the associated fitness benefits of reliable male
      coalitions with relatives or known partners, a feature that is absent in orang
      utans.

PMID- 22463134
TI  - Efficient estimation for rank-based regression with clustered data.
AB  - Rank-based inference is widely used because of its robustness. This article
      provides optimal rank-based estimating functions in analysis of clustered data
      with random cluster effects. The extensive simulation studies carried out to
      evaluate the performance of the proposed method demonstrate that it is robust to
      outliers and is highly efficient given the existence of strong cluster
      correlations. The performance of the proposed method is satisfactory even when
      the correlation structure is misspecified, or when heteroscedasticity in variance
      is present. Finally, a real dataset is analyzed for illustration.

PMID- 22463135
TI  - Measuring maximal eigenvalue distribution of Wishart random matrices with coupled
      lasers.
AB  - We determined the probability distribution of the combined output power from 25
      coupled fiber lasers and show that it agrees well with the Tracy-Widom and
      Majumdar-Vergassola distributions of the largest eigenvalue of Wishart random
      matrices with no fitting parameters. This was achieved with 500,000 measurements
      of the combined output power from the fiber lasers, that continuously changes
      with variations of the fiber lasers lengths. We show experimentally that for
      small deviations of the combined output power over its mean value the Tracy-Widom
      distribution is correct, while for large deviations the Majumdar-Vergassola
      distribution is correct.

PMID- 22463136
TI  - Nonuniversal heat conduction of one-dimensional lattices.
AB  - For one-dimensional nonlinear lattices with momentum conserving interparticle
      interactions, intensive studies have suggested that the heat conductivity kappa
      diverges with the system size L as kappa~L(alpha) and the value of alpha is
      universal. But in the Fermi-Pasta-Ulam-beta lattices with nearest-neighbor (NN)
      and next-nearest-neighbor (NNN) coupling, we find that alpha strongly depends on
      gamma, the ratio of the NNN coupling to the NN coupling. The correlation between
      the gamma-dependent heat conduction behavior and the in-band discrete breathers
      is also analyzed.

PMID- 22463137
TI  - Boundary layers in stochastic thermodynamics.
AB  - We study the problem of optimizing released heat or dissipated work in stochastic
      thermodynamics. In the overdamped limit these functionals have singular
      solutions, previously interpreted as protocol jumps. We show that a
      regularization, penalizing a properly defined acceleration, changes the jumps
      into boundary layers of finite width. We show that in the limit of vanishing
      boundary layer width no heat is dissipated in the boundary layer, while work can
      be done. We further give an alternative interpretation of the fact that the
      optimal protocols in the overdamped limit are given by optimal deterministic
      transport (Burgers equation).

PMID- 22463138
TI  - Energy dissipation in small-scale shape-change dynamics.
AB  - Shape is an important feature of physical systems, although very seldom is it
      addressed in the framework of a quantitative description approach. In this paper
      we propose to interpret the shape of things as a physical manifestation of the
      content of information associated with each thing and show that a change of shape
      in a physical system is necessarily connected with a change of its entropy and
      thus involves energy. We estimate the amount of energy dissipated during a shape
      change and propose experimental tests to be performed in nanoscale systems to
      verify this prediction by measuring the expected dissipation in a few simple
      cases. Relevant implications in the design of future zero-power logic switches
      are discussed.

PMID- 22463139
TI  - Nuclear magnetic resonance relaxometry as a method of measuring translational
      diffusion coefficients in liquids.
AB  - By application of the field-cycling technique, we measure the dispersion of the
      (1)H nuclear magnetic resonance (NMR) spin-lattice relaxation time T(1)(omega)
      for a series of molecular liquids. We demonstrate that such NMR relaxometry
      studies can be used for determining diffusion coefficients. A broad frequency
      range of 10 kHz-20 MHz is covered. By scanning T(1)(omega) one directly probes
      the spectral density of the diffusion processes. The value of the diffusion
      coefficient D can be determined from a linear dependence of the (1)H spin-lattice
      relaxation rate on the square root of the frequency at which it is measured. The
      power of this method lies in its simplicity, which allows one to determine D(T)
      independently of the diffusive model. The results obtained are in very good
      agreement with those of field gradient NMR methods.

PMID- 22463140
TI  - Bottlenecks in granular flow: when does an obstacle increase the flow rate in an
      hourglass?
AB  - Bottlenecks occur in a wide range of situations from pedestrians, ants, cattle,
      and traffic flow to the transport of granular materials. We examine granular flow
      across a bottleneck using simulations of monodisperse disks. Contrary to
      expectations but consistent with previous work, we find that the flow rate across
      a bottleneck actually increases if an obstacle is optimally placed before it.
      Using the hourglass theory and a velocity-density relation, we show that the peak
      flow rate corresponds to a transition from free flow to congested flow, similar
      to the phase transition in traffic flow.

PMID- 22463141
TI  - Size dependence of the propulsion velocity for catalytic Janus-sphere swimmers.
AB  - The propulsion velocity of active colloids that asymmetrically catalyze a
      chemical reaction is probed experimentally as a function of their sizes. It is
      found that over the experimentally accessible range, the velocity decays as a
      function of size, with a rate that is compatible with an inverse size dependence.
      A diffusion-reaction model for the concentrations of the fuel and waste molecules
      that takes into account a two-step process for the asymmetric catalytic activity
      on the surface of the colloid is shown to predict a similar behavior for colloids
      at the large size limit, with a saturation for smaller sizes.

PMID- 22463142
TI  - Single-file diffusion and kinetics of template-assisted assembly of colloids.
AB  - We report computer simulation studies of the kinetics of ordering of a two
      dimensional system of particles on a template with a one-dimensional periodic
      pattern. In equilibrium, one obtains a reentrant liquid-solid-liquid phase
      transition as the strength of the substrate potential is varied. We show that
      domains of crystalline order grow as ~t(1/z), with z~4, with a possible crossover
      to z~2 at late times. We argue that the t(1/4) law originates from single-file
      motion and annihilation of defect pairs of opposite topological charge along
      channels created by the template.

PMID- 22463143
TI  - Field-induced breakup of emulsion droplets stabilized by colloidal particles.
AB  - We simulate the response of a particle-stabilized emulsion droplet in an external
      force field, such as gravity, acting equally on all N particles. We show that the
      field strength required for breakup (at fixed initial area fraction) decreases
      markedly with droplet size, because the forces act cumulatively, not
      individually, to detach the interfacial particles. The breakup mode involves the
      collective destabilization of a solidified particle raft occupying the lower part
      of the droplet, leading to a critical force per particle that scales
      approximately as N(-1/2).

PMID- 22463144
TI  - Stabilization of blue phases by the variation of elastic constants.
AB  - We study theoretically the effect of the variation of the elastic constants on
      the stability of cholesteric blue phases (BPs). We demonstrate that the stability
      of BPs is greatly enhanced when the bend elastic constant K(33) is smaller, in
      agreement with recent experimental findings. Larger splay (K(11)) and twist
      (K(22)) elastic constants also stabilize BPs. Our argument sheds light on the
      subtle effect of the variation of the elastic constants on the stability of BPs,
      and could guide the synthesis of liquid crystals with a wider temperature range
      of stable BPs.

PMID- 22463145
TI  - Conformational modes in biomolecules: dynamics and approximate invariance.
AB  - Understanding the physical mechanisms behind the folding and conformational
      dynamics of biomolecules is one of the major unsolved challenges of soft matter
      theory. In this contribution, a theoretical framework for biomolecular dynamics
      is introduced, employing selected aspects of statistical mechanics,
      dimensionality reduction, the perturbation theory, and the theory of matrices.
      Biomolecular dynamics is represented by time-dependent orthogonal conformational
      modes, the dynamics of the modes is investigated, and invariant properties that
      persist are identified. As an example, the dynamics of a human prion protein is
      considered. The theory provides a rigorous background for assessing the stable
      dynamical properties of biomolecules, such as their coarse-grained structure,
      through a multiscale approach using short subnanosecond segments of molecular
      dynamics trajectories. Furthermore, the paper offers a theoretical platform for
      models of conformational changes in macromolecules, which may allow complementing
      molecular dynamics simulations.

PMID- 22463146
TI  - Self-sustained peristaltic waves: explicit asymptotic solutions.
AB  - A simple nonlinear model for the coupled problem of fluid flow and contractile
      wall deformation is proposed to describe peristalsis. In the context of the model
      the ability of a transporting system to perform autonomous peristaltic pumping is
      interpreted as the ability to propagate sustained waves of wall deformation.
      Piecewise-linear approximations of nonlinear functions are used to analytically
      demonstrate the existence of traveling-wave solutions. Explicit formulas are
      derived which relate the speed of self-sustained peristaltic waves to the
      rheological properties of the transporting vessel and the transported fluid. The
      results may contribute to the development of diagnostic and therapeutic
      procedures for cases of peristaltic motility disorders.

PMID- 22463147
TI  - Finite-size scaling in asymmetric systems of percolating sticks.
AB  - We investigate finite-size scaling in percolating widthless stick systems with
      variable aspect ratios in an extensive Monte Carlo simulation study. A
      generalized scaling function is introduced to describe the scaling behavior of
      the percolation distribution moments and probability at the percolation
      threshold. We show that the prefactors in the generalized scaling function depend
      on the system aspect ratio and exhibit features that are generic to the whole
      class of the percolating systems. In particular, we demonstrate the existence of
      a characteristic aspect ratio for which percolation probability at the threshold
      is scale invariant and definite parity of the prefactors in the generalized
      scaling function for the first two percolation probability moments.

PMID- 22463148
TI  - Modified fluctuation-dissipation and Einstein relation at nonequilibrium steady
      states.
AB  - Starting from the pioneering work of Agarwal [G. S. Agarwal, Zeitschrift fur
      Physik 252, 25 (1972)], we present a unified derivation of a number of modified
      fluctuation-dissipation relations (MFDR) that relate response to small
      perturbations around nonequilibrium steady states to steady-state correlations.
      Using this formalism we show the equivalence of velocity forms of MFDR derived
      using continuum Langevin and discrete master equation dynamics. The resulting
      additive correction to the Einstein relation is exemplified using a flashing
      ratchet model of molecular motors.

PMID- 22463149
TI  - Effective confinement as origin of the equivalence of kinetic temperature and
      fluctuation-dissipation ratio in a dense shear-driven suspension.
AB  - We study response and velocity autocorrelation functions for a tagged particle in
      a shear driven suspension governed by underdamped stochastic dynamics. We follow
      the idea of an effective confinement in dense suspensions and exploit a time
      scale separation between particle reorganization and vibrational motion. This
      allows us to approximately derive the fluctuation-dissipation theorem in a
      "hybrid" form involving the kinetic temperature as an effective temperature and
      an additive correction term. We show numerically that even in a moderately dense
      suspension the latter is negligible. We discuss similarities and differences with
      a simple toy model, a single trapped particle in shear flow.

PMID- 22463150
TI  - Nonequilibrium thermodynamics of feedback control.
AB  - We establish a general theory of feedback control on classical stochastic
      thermodynamic systems and generalize nonequilibrium equalities such as the
      fluctuation theorem and the Jarzynski equality in the presence of feedback
      control with multiple measurements. Our results are generalizations of the
      previous relevant works to the situations with general measurements and multiple
      heat baths. The obtained equalities involve additional terms that characterize
      the information obtained by measurements or the efficacy of feedback control. A
      generalized Szilard engine and a feedback-controlled ratchet are shown to satisfy
      the derived equalities.

PMID- 22463151
TI  - Triviality problem and high-temperature expansions of higher susceptibilities for
      the Ising and scalar-field models in four-, five-, and six-dimensional lattices.
AB  - High-temperature expansions are presently the only viable approach to the
      numerical calculation of the higher susceptibilities for the spin and the scalar
      field models on high-dimensional lattices. The critical amplitudes of these
      quantities enter into a sequence of universal amplitude ratios that determine the
      critical equation of state. We have obtained a substantial extension, through
      order 24, of the high-temperature expansions of the free energy (in presence of a
      magnetic field) for the Ising models with spin s>=1/2 and for the lattice scalar
      field theory with quartic self-interaction on the simple-cubic and the body
      centered-cubic lattices in four, five, and six spatial dimensions. A numerical
      analysis of the higher susceptibilities obtained from these expansions yields
      results consistent with the widely accepted ideas, based on the renormalization
      group and the constructive approach to Euclidean quantum field theory, concerning
      the no-interaction ("triviality") property of the continuum (scaling) limit of
      spin-s Ising and lattice scalar-field models at and above the upper critical
      dimensionality.

PMID- 22463152
TI  - Cavity approach to sphere packing in Hamming space.
AB  - In this paper we study the hard sphere packing problem in the Hamming space by
      the cavity method. We show that both the replica symmetric and the replica
      symmetry breaking approximations give maximum rates of packing that are
      asymptotically the same as the lower bound of Gilbert and Varshamov. Consistently
      with known numerical results, the replica symmetric equations also suggest a
      crystalline solution, where for even diameters the spheres are more likely to be
      found in one of the subspaces (even or odd) of the Hamming space. These
      crystalline packings can be generated by a recursive algorithm which finds
      maximum packings in an ultrametric space. Finally, we design a message passing
      algorithm based on the cavity equations to find dense packings of hard spheres.
      Known maximum packings are reproduced efficiently in nontrivial ranges of
      dimensions and number of spheres.

PMID- 22463153
TI  - Pattern formation in fast-growing sandpiles.
AB  - We study the patterns formed by adding N sand grains at a single site on an
      initial periodic background in the Abelian sandpile models, and relaxing the
      configuration. When the heights at all sites in the initial background are low
      enough, one gets patterns showing proportionate growth, with the diameter of the
      pattern formed growing as N(1/d) for large N, in d dimensions. On the other hand,
      if sites with maximum stable height in the starting configuration form an
      infinite cluster, we get avalanches that do not stop. In this paper we describe
      our unexpected finding of an interesting class of backgrounds in two dimensions
      that show an intermediate behavior: For any N, the avalanches are finite, but the
      diameter of the pattern increases as N(alpha), for large N, with 1/2<alpha<=1.
      Different values of alpha can be realized on different backgrounds, and the
      patterns still show proportionate growth. The noncompact nature of growth
      simplifies their analysis significantly. We characterize the asymptotic pattern
      exactly for one illustrative example with alpha=1.

PMID- 22463154
TI  - Heat and work fluctuations for a harmonic oscillator.
AB  - The formalism of Kundu et al. [J. Stat. Mech. P03007 (2011)], for computing the
      large deviations of heat flow in harmonic systems, is applied to the case of
      single Brownian particle in a harmonic trap and coupled to two heat baths at
      different temperatures. The large-tau form of the moment generating function <e(
      lambdaQ)>~g(lambda)exp[tauMU(lambda)], of the total heat flow Q from one of the
      baths to the particle in a given time interval tau, is studied and exact explicit
      expressions are obtained for both MU(lambda) and g(lambda). For a special case of
      the single particle problem that corresponds to the work done by an external
      stochastic force on a harmonic oscillator coupled to a thermal bath, the large
      tau form of the moment generating function is analyzed to obtain the exact large
      deviation function as well as the complete asymptotic forms of the probability
      density function of the work.

PMID- 22463155
TI  - Threshold of hierarchical percolating systems.
AB  - Many modern nanostructured materials and doped polymers are morphologically too
      complex to be interpreted by classical percolation theory. Here, we develop the
      concept of a hierarchical percolating (percolation-within-percolation) system to
      describe such complex materials and illustrate how to generalize the conventional
      percolation to double-level percolation. Based on Monte Carlo simulations, we
      find that the double-level percolation threshold is close to, but definitely
      larger than, the product of the local percolation thresholds for the two enclosed
      single-level systems. The deviation may offer alternative insights into physics
      concerning infinite clusters and open up new research directions for percolation
      theory.

PMID- 22463156
TI  - Generalization of the Einstein relation for single trajectories in deterministic
      subdiffusion.
AB  - Diffusion coefficients are intrinsically random in subdiffusion attributable to
      power-law trapping. Using deterministic biased and unbiased diffusion models, we
      investigate the Einstein relation for single trajectories in subdiffusion. The
      difference in the generalized Lyapunov exponent between biased and unbiased
      deterministic diffusions is related to the velocity under a bias. By Hopf's
      ergodic theorem, the ratios between the velocities and the Lyapunov exponents for
      single trajectories converge to a universal constant, which is proportional to
      the strength of the bias. Based on a certain transport coefficient obtained from
      a single trajectory, we provide a relation for the transport coefficients divided
      by the Lyapunov exponent and generalize the Einstein relation for single
      trajectories.

PMID- 22463157
TI  - Cooperative behavior in evolutionary snowdrift games with the unconditional
      imitation rule on regular lattices.
AB  - We study an evolutionary snowdrift game with the unconditional imitation updating
      rule on regular lattices. Detailed numerical simulations establish the structure
      of plateaus and discontinuous jumps of the equilibrium cooperation frequency f(c)
      as a function of the cost-to-benefit ratio r. By analyzing the stability of local
      configurations, it is found that the transitions occur at values of r at which
      there are changes in the ranking of the payoffs to the different local
      configurations of agents using different strategies. Nonmonotonic behavior of
      f(c)(r) at the intermediate range of r is analyzed in terms of the formation of
      blocks of agents using the cooperative strategy that are stabilized by agents
      inside the block due to the updating rule. For random initial condition with 50%
      50% agents of different strategies randomly dispersed, cooperation persists in
      the whole range of r and the level of cooperation is higher than that in the well
      mixed case in a wide range of r. These results are in sharp contrast to those
      based on the replicator updating rule. The sensitivity to initial states with
      different fractions of cooperative agents is also discussed. The results serve to
      illustrate that both the spatial structure and the updating rule are important in
      determining the level of cooperation in a competing population. When extreme
      initial states are used where there are very few agents of a strategy in a
      background of the opposite strategy, the result would depend on the stability of
      the clusters formed by the initially minority agents.

PMID- 22463158
TI  - Quantifying reversibility in a phase-separating lattice gas: an analogy with self
      assembly.
AB  - We present dynamic measurements of a lattice gas during phase separation, which
      we use as an analogy for self-assembly of equilibrium ordered structures. We use
      two approaches to quantify the degree of reversibility of this process: First, we
      count events in which bonds are made and broken; second, we use correlation
      response measurements and fluctuation-dissipation ratios to probe reversibility
      during different time intervals. We show how correlation and response functions
      can be related directly to microscopic (ir)reversibility and we discuss the time
      dependence and observable dependence of these measurements, including the role of
      fast and slow degrees of freedom during assembly.

PMID- 22463159
TI  - Continuous universality in nonequilibrium relaxational dynamics of O2 symmetric
      systems.
AB  - We elucidate a nonconserved relaxational nonequilibrium dynamics of a O(2)
      symmetric model. We drive the system out of equilibrium by introducing a nonzero
      noise cross correlation of amplitude D(*) in a stochastic Langevin description of
      the system, while maintaining the O(2) symmetry of the order parameter space. By
      performing dynamic renormalization group calculations in a field-theoretic set
      up, we analyze the ensuing nonequilibrium steady states and evaluate the scaling
      exponents near the critical point, which now depend explicitly on D(*). Since the
      latter remains unrenormalized, we obtain universality classes varying
      continuously with D(*). More interestingly, by changing D(*) continuously from
      zero, we can make our system move away from its equilibrium behavior (i.e., when
      D(*)=0) continuously and incrementally.

PMID- 22463160
TI  - Phase transitions in two-dimensional Z(N) vector models for N>4.
AB  - We investigate both analytically and numerically the renormalization group
      equations in two-dimensional (2D) Z(N) vector models. The position of the
      critical points of the two phase transitions for N>4 is established and the
      critical index nu is computed. For N=7 and 17 the critical points are located by
      Monte Carlo simulations, and some of the corresponding critical indices are
      determined. The behavior of the helicity modulus is studied for N=5, 7, and 17.
      Using these and other available Monte Carlo data we discuss the scaling of the
      critical points with N and some other open theoretical problems.

PMID- 22463161
TI  - Critical behavior of a three-dimensional hardcore-cylinder composite system.
AB  - In this work the critical indices beta, gamma, and nu for a three-dimensional
      (3D) hardcore cylinder composite system with short-range interaction have been
      obtained. In contrast to the 2D stick system and the 3D hardcore cylinder system,
      the determined critical exponents do not belong to the same universality class as
      the lattice percolation, although they obey the common hyperscaling relation for
      a 3D system. It is observed that the value of the correlation length exponent is
      compatible with the predictions of the mean field theory. It is also shown that,
      by using the Alexander-Orbach conjuncture, the relation between the conductivity
      and the correlation length critical exponents has a typical value for a 3D
      lattice system.

PMID- 22463162
TI  - Phase transitions in crowd dynamics of resource allocation.
AB  - We define and study a class of resource allocation processes where gN agents, by
      repeatedly visiting N resources, try to converge to an optimal configuration
      where each resource is occupied by at most one agent. The process exhibits a
      phase transition, as the density g of agents grows, from an absorbing to an
      active phase. In the latter, even if the number of resources is in principle
      enough for all agents (g<1), the system never settles to a frozen configuration.
      We recast these processes in terms of zero-range interacting particles, studying
      analytically the mean field dynamics and investigating numerically the phase
      transition in finite dimensions. We find a good agreement with the critical
      exponents of the stochastic fixed-energy sandpile. The lack of coordination in
      the active phase also leads to a nontrivial faster-is-slower effect.

PMID- 22463163
TI  - Quantum statistics and thermodynamics in the harmonic approximation.
AB  - We describe a method to compute thermodynamic quantities in the harmonic
      approximation for identical bosons and fermions in an external confining field.
      We use the canonical partition function where only energies and their
      degeneracies enter. The number of states of given energy and symmetry is found by
      separating the center-of-mass motion, and by counting the remaining states of
      given symmetry and excitation energy of the relative motion. The oscillator
      frequencies that enter the harmonic Hamiltonian can be derived from realistic
      model parameters, and the method corresponds to an effective interaction approach
      based on harmonic interactions. To demonstrate the method, we apply it to systems
      in two dimensions. Numerical calculations are compared to a brute force method,
      which is considerably more computationally intensive.

PMID- 22463164
TI  - Anomalous diffusion in systems driven by the stable Levy noise with a finite
      noise relaxation time and inertia.
AB  - Dynamical systems driven by a general Levy stable noise are considered. The
      inertia is included and the noise, represented by a generalized Ornstein
      Uhlenbeck process, has a finite relaxation time. A general linear problem (the
      additive noise) is solved: the resulting distribution converges with time to the
      distribution for the white-noise, massless case. Moreover, a multiplicative noise
      is discussed. It can make the distribution steeper and the variance, which is
      finite, depends sublinearly on time (subdiffusion). For a small mass, a white
      noise limit corresponds to the Stratonovich interpretation. On the other hand,
      the distribution tails agree with the Ito interpretation if the inertia is very
      large. An escape time from the potential well is calculated.

PMID- 22463165
TI  - Potential field cellular automata model for pedestrian flow.
AB  - This paper proposes a cellular automata model of pedestrian flow that defines a
      cost potential field, which takes into account the costs of travel time and
      discomfort, for a pedestrian to move to an empty neighboring cell. The
      formulation is based on a reconstruction of the density distribution and the
      underlying physics, including the rule for resolving conflicts, which is
      comparable to that in the floor field cellular automaton model. However, we
      assume that each pedestrian is familiar with the surroundings, thereby minimizing
      his or her instantaneous cost. This, in turn, helps reduce the randomness in
      selecting a target cell, which improves the existing cellular automata modelings,
      together with the computational efficiency. In the presence of two pedestrian
      groups, which are distinguished by their destinations, the cost distribution for
      each group is magnified due to the strong interaction between the two groups. As
      a typical phenomenon, the formation of lanes in the counter flow is reproduced.

PMID- 22463166
TI  - Random pinning in glassy spin models with plaquette interactions.
AB  - We use a random pinning procedure to study amorphous order in two glassy spin
      models. On increasing the concentration of pinned spins at constant temperature,
      we find a sharp crossover (but no thermodynamic phase transition) from bulk
      relaxation to localization in a single state. At low temperatures, both models
      exhibit scaling behavior. We discuss the growing length and time scales
      associated with amorphous order, and the fraction of pinned spins required to
      localize the system in a single state. These results, obtained for finite
      dimensional interacting models, provide a theoretical scenario for the effect of
      random pinning that differs qualitatively from previous approaches based either
      on mean-field, mode-coupling, or renormalization group treatments.

PMID- 22463167
TI  - Nonuniversality of roughness exponent of quasistatic fracture surfaces.
AB  - Numerous experiments have indicated that the fracture front (in three dimensions)
      and crack lines (in two dimensions) in disordered solids and rocklike materials
      is rough. It has been argued that the roughness exponent zeta is universal. Using
      extensive simulations of a two-dimensional model, we provide strong evidence that
      if extended correlations and anisotropy-two features that are prevalent in many
      materials-are incorporated in the models that are used in the numerical
      simulation of crack propagation, then zeta will vary considerably with the extent
      of the correlations and anisotropy. The results are consistent with recent
      experiments that also indicate deviations of zeta from its supposedly universal
      value, as well as with the data from rock samples.

PMID- 22463168
TI  - Nonequilibrium phase transition of contact processes with the Kauffman NK model.
AB  - We consider a multistate contact process (CP) in which new particles are created
      with probabilities that depend on the fitness of the parent particle and with
      mutations that occur at the time of creation. The fitness is determined by the
      Kauffman NK model. Using Monte Carlo simulations, we show that such an
      evolutional CP exhibits critical behaviors that differ from the basic CP. In
      addition, we present numerical results suggesting that the fitness averaged over
      surviving particles exhibits a maximum value at the critical point.

PMID- 22463169
TI  - Generalized Lyapunov exponents of the random harmonic oscillator: cumulant
      expansion approach.
AB  - The cumulant expansion is used to estimate generalized Lyapunov exponents of the
      random-frequency harmonic oscillator. Three stochastic processes are considered:
      Gaussian white noise, Ornstein-Uhlenbeck, and Poisson shot noise. In some cases,
      nontrivial numerical difficulties arise. These are mostly solved by implementing
      an appropriate importance-sampling Monte Carlo scheme. We analyze the relation
      between random-frequency oscillators and many-particle systems with pairwise
      interactions like the Lennard-Jones gas.

PMID- 22463170
TI  - Demographic fluctuations in a population of anomalously diffusing individuals.
AB  - The phenomenon of spatial clustering induced by death and reproduction in a
      population of anomalously diffusing individuals is studied analytically. The
      possibility of social behaviors affecting the migration strategies has been taken
      into exam, in the case that anomalous diffusion is produced by means of a
      continuous time random walk (CTRW). In the case of independently diffusing
      individuals, the dynamics appears to coincide with that of (dying and
      reproducing) Brownian walkers. In the strongly social case, the dynamics
      coincides with that of nonmigrating individuals. In both limits, the growth rate
      of the fluctuations becomes independent of the Hurst exponent of the CTRW. The
      social behaviors that arise when transport in a population is induced by a
      spatial distribution of random traps have been analyzed.

PMID- 22463171
TI  - Microscopic approach to nonlinear reaction-diffusion: the case of morphogen
      gradient formation.
AB  - We develop a microscopic theory for reaction-diffusion (RD) processes based on a
      generalization of Einstein's master equation [Ann. Phys. 17, 549 (1905)] with a
      reactive term and show how the mean-field formulation leads to a generalized RD
      equation with nonclassical solutions. For the nth-order annihilation reaction
      A+A+A+...+A->0, we obtain a nonlinear reaction-diffusion equation for which we
      discuss scaling and nonscaling formulations. We find steady states with solutions
      either exhibiting long-range power-law behavior showing the relative dominance of
      subdiffusion over reaction effects in constrained systems or, conversely,
      solutions that go to zero a finite distance from the source, i.e., having finite
      support of the concentration distribution, describing situations in which
      diffusion is slow and extinction is fast. Theoretical results are compared with
      experimental data for morphogen gradient formation.

PMID- 22463172
TI  - Level-number variance and spectral compressibility in a critical two-dimensional
      random-matrix model.
AB  - We study level-number variance in a two-dimensional random matrix model
      characterized by a power-law decay of the matrix elements. The amplitude of the
      decay is controlled by the parameter b. We find analytically that at small values
      of b the level number variance behaves linearly, with the compressibility chi
      between 0 and 1, which is typical for critical systems. For large values of b, we
      derive that chi=0, as one would normally expect in the metallic phase. Using
      numerical simulations we determine the critical value of b at which the
      transition between these two phases occurs.

PMID- 22463173
TI  - Master equation for a bistable chemical system with perturbed particle velocity
      distribution function.
AB  - We present a modified master equation for a homogeneous gaseous reactive system
      which includes nonequilibrium corrections due to the reaction-induced
      perturbation of the particle velocity distribution function. For the Schlogl
      model, the modified stochastic approach predicts nonequilibrium-induced
      transitions between different dynamical regimes, including the transformation of
      a monostable system into a bistable one, and vice versa. These predictions are
      confirmed by the comparison with microscopic simulations using the direct
      simulation Monte Carlo method. Compared to microscopic simulations of the
      particle dynamics, the modified master equation approach proves to be much more
      efficient.

PMID- 22463174
TI  - Efficiency of a thermodynamic motor at maximum power.
AB  - Several recent theories address the efficiency of a macroscopic thermodynamic
      motor at maximum power and question the so-called Curzon-Ahlborn (CA) efficiency.
      Considering the entropy exchanges and productions in an n-sources motor, we study
      the maximization of its power and show that the controversies are partly due to
      some imprecision in the maximization variables. When power is maximized with
      respect to the system temperatures, these temperatures are proportional to the
      square root of the corresponding source temperatures, which leads to the CA
      formula for a bithermal motor. On the other hand, when power is maximized with
      respect to the transition durations, the Carnot efficiency of a bithermal motor
      admits the CA efficiency as a lower bound, which is attained if the duration of
      the adiabatic transitions can be neglected. Additionally, we compute the
      energetic efficiency, or "sustainable efficiency," which can be defined for n
      sources, and we show that it has no other universal upper bound than 1, but that
      in certain situations, which are favorable for power production, it does not
      exceed 1/2.

PMID- 22463175
TI  - Densest binary sphere packings.
AB  - The densest binary sphere packings in the alpha-x plane of small to large sphere
      radius ratio alpha and small sphere relative concentration x have historically
      been very difficult to determine. Previous research had led to the prediction
      that these packings were composed of a few known "alloy" phases including, for
      example, the AlB(2) (hexagonal omega), HgBr(2), and AuTe(2) structures, and to
      XY(n) structures composed of close-packed large spheres with small spheres (in a
      number ratio of n to 1) in the interstices, e.g., the NaCl packing for n=1.
      However, utilizing an implementation of the Torquato-Jiao sphere-packing
      algorithm [Torquato and Jiao, Phys. Rev. E 82, 061302 (2010)], we have discovered
      that many more structures appear in the densest packings. For example, while all
      previously known densest structures were composed of spheres in small to large
      number ratios of one to one, two to one, and very recently three to one, we have
      identified densest structures with number ratios of seven to three and five to
      two. In a recent work [Hopkins et al., Phys. Rev. Lett. 107, 125501 (2011)], we
      summarized these findings. In this work, we present the structures of the densest
      known packings and provide details about their characteristics. Our findings
      demonstrate that a broad array of different densest mechanically stable
      structures consisting of only two types of components can form without any
      consideration of attractive or anisotropic interactions. In addition, the
      structures that we have identified may correspond to currently unidentified
      stable phases of certain binary atomic and molecular systems, particularly at
      high temperatures and pressures.

PMID- 22463176
TI  - Mathematical modeling and numerical computation of narrow escape problems.
AB  - The narrow escape problem refers to the problem of calculating the mean first
      passage time (MFPT) needed for an average Brownian particle to leave a domain
      with an insulating boundary containing N small well-separated absorbing windows,
      or traps. This mean first passage time satisfies the Poisson partial differential
      equation subject to a mixed Dirichlet-Neumann boundary condition on the domain
      boundary, with the Dirichlet condition corresponding to absorbing traps. In the
      limit of small total trap size, a common asymptotic theory is presented to
      calculate the MFPT in two-dimensional domains and in the unit sphere. The
      asymptotic MFPT formulas depend on mutual trap locations, allowing for global
      optimization of trap locations. Although the asymptotic theory for the MFPT was
      developed in the limit of asymptotically small trap radii, and under the
      assumption that the traps are well-separated, a comprehensive study involving
      comparison with full numerical simulations shows that the full numerical and
      asymptotic results for the MFPT are within 1% accuracy even when total trap size
      is only moderately small, and for traps that may be rather close together. This
      close agreement between asymptotic and numerical results at finite, and not
      necessarily asymptotically small, values of the trap size clearly illustrates one
      of the key side benefits of a theory based on a systematic asymptotic analysis.
      In addition, for the unit sphere, numerical results are given for the optimal
      configuration of a collection of traps on the surface of a sphere that minimizes
      the average MFPT. The case of N identical traps and a pattern of traps with two
      different sizes are considered. The effect of trap fragmentation on the average
      MFPT is also discussed.

PMID- 22463177
TI  - Transition of velocity distributions in collapsing self-gravitating N-body
      systems.
AB  - By means of N-body simulations, we study the evolution of gravity-dominated
      systems from an early relaxation to a collapse, focusing on the velocity
      distributions and thermodynamic properties. To simulate the dynamical evolution,
      we consider self-gravitating small N-body systems enclosed in a spherical
      container with adiabatic or semipermeable walls. It is demonstrated that in the
      early relaxation process, the velocity distribution is non-Gaussian and q
      Gaussian, since the system is in quasiequilibrium states (here q is the Tsallis
      entropic parameter). Thereafter, the velocity distribution undergoes higher non
      Gaussian distributions, especially when the core forms rapidly in the collapse
      process; i.e., q tends to be larger than that for the quasiequilibrium state,
      since the velocity distribution further deviates from Gaussian. However, after
      the core forms sufficiently, the velocity distribution gradually relaxes toward a
      Gaussian-like distribution. Accordingly, the velocity distribution evolves from a
      non-Gaussian distribution through a higher non-Gaussian distribution to a
      Gaussian-like distribution; i.e., the velocity distribution does not
      monotonically relax toward a Gaussian-like distribution in our collapse
      simulations. We clearly show such a transition of the velocity distribution,
      based not only on the Tsallis entropic parameter but also on the ratio of
      velocity moments. We also find that a negative specific heat occurs in a collapse
      process with mass and energy loss (such as the escape of stars from globular
      clusters), even if the velocity distribution is Gaussian-like.

PMID- 22463178
TI  - Linear response theory for long-range interacting systems in quasistationary
      states.
AB  - Long-range interacting systems, while relaxing to equilibrium, often get trapped
      in long-lived quasistationary states which have lifetimes that diverge with the
      system size. In this work, we address the question of how a long-range system in
      a quasistationary state (QSS) responds to an external perturbation. We consider a
      long-range system that evolves under deterministic Hamilton dynamics. The
      perturbation is taken to couple to the canonical coordinates of the individual
      constituents. Our study is based on analyzing the Vlasov equation for the single
      particle phase-space distribution. The QSS represents a stable stationary
      solution of the Vlasov equation in the absence of the external perturbation. In
      the presence of small perturbation, we linearize the perturbed Vlasov equation
      about the QSS to obtain a formal expression for the response observed in a single
      particle dynamical quantity. For a QSS that is homogeneous in the coordinate, we
      obtain an explicit formula for the response. We apply our analysis to a
      paradigmatic model, the Hamiltonian mean-field model, which involves particles
      moving on a circle under Hamiltonian dynamics. Our prediction for the response of
      three representative QSSs in this model (the water-bag QSS, the Fermi-Dirac QSS,
      and the Gaussian QSS) is found to be in good agreement with N-particle
      simulations for large N. We also show the long-time relaxation of the water-bag
      QSS to the Boltzmann-Gibbs equilibrium state.

PMID- 22463179
TI  - Improving stochastic estimates with inference methods: calculating matrix
      diagonals.
AB  - Estimating the diagonal entries of a matrix, that is not directly accessible but
      only available as a linear operator in the form of a computer routine, is a
      common necessity in many computational applications, especially in image
      reconstruction and statistical inference. Here, methods of statistical inference
      are used to improve the accuracy or the computational costs of matrix probing
      methods to estimate matrix diagonals. In particular, the generalized Wiener
      filter methodology, as developed within information field theory, is shown to
      significantly improve estimates based on only a few sampling probes, in cases in
      which some form of continuity of the solution can be assumed. The strength,
      length scale, and precise functional form of the exploited autocorrelation
      function of the matrix diagonal is determined from the probes themselves. The
      developed algorithm is successfully applied to mock and real world problems.
      These performance tests show that, in situations where a matrix diagonal has to
      be calculated from only a small number of computationally expensive probes, a
      speedup by a factor of 2 to 10 is possible with the proposed method.

PMID- 22463180
TI  - Geometrical properties of the Potts model during the coarsening regime.
AB  - We study the dynamic evolution of geometric structures in a polydegenerate system
      represented by a q-state Potts model with nonconserved order parameter that is
      quenched from its disordered into its ordered phase. The numerical results
      obtained with Monte Carlo simulations show a strong relation between the
      statistical properties of hull perimeters in the initial state and during
      coarsening: The statistics and morphology of the structures that are larger than
      the averaged ones are those of the initial state, while the ones of small
      structures are determined by the curvature-driven dynamic process. We link the
      hull properties to the ones of the areas they enclose. We analyze the linear von
      Neumann-Mullins law, both for individual domains and on the average, concluding
      that its validity, for the later case, is limited to domains with number of sides
      around 6, while presenting stronger violations in the former case.

PMID- 22463181
TI  - Diffusion in a quasi-one-dimensional system on a periodic substrate.
AB  - The diffusion of charged particles interacting through a repulsive Yukawa
      potential, exp(-r/lambda)/r, confined by a parabolic potential in the y direction
      and subjected to a periodic substrate potential in the x direction is
      investigated. Langevin dynamic simulations are used to investigate the effect of
      the particle density, the amplitude of the periodic substrate, and the range of
      the interparticle interaction potential on the diffusive behavior of the
      particles. We found that in general the diffusion is suppressed with increasing
      the amplitude of the periodic potential, but for specific values of the strength
      of the substrate potential a remarkable increase of the diffusion is found with
      increasing the periodic potential amplitude. In addition, we found a strong
      dependence of the diffusion on the specific arrangement of the particles, e.g.,
      single-chain versus multichain configuration. For certain particle
      configurations, a reentrant behavior of the diffusion is found as a function of
      the substrate strength due to structural transitions in the ordering of the
      particles.

PMID- 22463182
TI  - Non-Gaussianity and dynamical trapping in locally activated random walks.
AB  - We propose a minimal model of locally activated diffusion, in which the diffusion
      coefficient of a one-dimensional Brownian particle is modified in a prescribed
      way-either increased or decreased-upon each crossing of the origin. Such a local
      mobility decrease arises in the formation of atherosclerotic plaques due to
      diffusing macrophage cells accumulating lipid particles. We show that spatially
      localized mobility perturbations have remarkable consequences on diffusion at all
      scales, such as the emergence of a non-Gaussian multipeaked probability
      distribution and a dynamical transition to an absorbing static state. In the
      context of atherosclerosis, this dynamical transition can be viewed as a minimal
      mechanism that causes macrophages to aggregate in lipid-enriched regions and
      thereby to the formation of atherosclerotic plaques.

PMID- 22463183
TI  - Transmission probability through a Levy glass and comparison with a Levy walk.
AB  - Recent experiments on the propagation of light over a distance L through a random
      packing of spheres with a power-law distribution of radii (a so-called Levy
      glass) have found that the transmission probability T?1/L(gamma) scales
      superdiffusively (gamma<1). The data has been interpreted in terms of a Levy
      walk. We present computer simulations to demonstrate that diffusive scaling
      (gamma~1) can coexist with a divergent second moment of the step size
      distribution [p(s)?1/s(1+alpha) with alpha<2]. This finding is in accord with
      analytical predictions for the effect of step size correlations, but deviates
      from what one would expect for a Levy walk of independent steps.

PMID- 22463184
TI  - Stochastic queueing-theory approach to human dynamics.
AB  - Recently, numerous studies have shown that human dynamics cannot be described
      accurately by exponential laws. For instance, Barabasi [Nature (London) 435, 207
      (2005)] demonstrates that waiting times of tasks to be performed by a human are
      more suitably modeled by power laws. He presumes that these power laws are caused
      by a priority selection mechanism among the tasks. Priority models are well
      developed in queueing theory (e.g., for telecommunication applications), and this
      paper demonstrates the (quasi-)immediate applicability of such a stochastic
      priority model to human dynamics. By calculating generating functions and by
      studying them in their dominant singularity, we prove that nonexponential tails
      result naturally. Contrary to popular belief, however, these are not necessarily
      triggered by the priority selection mechanism.

PMID- 22463185
TI  - Multiple extinction routes in stochastic population models.
AB  - Isolated populations ultimately go extinct because of the intrinsic noise of
      elementary processes. In multipopulation systems extinction of a population may
      occur via more than one route. We investigate this generic situation in a simple
      predator-prey (or infected-susceptible) model. The predator and prey populations
      may coexist for a long time, but ultimately both go extinct. In the first
      extinction route the predators go extinct first, whereas the prey thrive for a
      long time and then also go extinct. In the second route the prey go extinct
      first, causing a rapid extinction of the predators. Assuming large subpopulation
      sizes in the coexistence state, we compare the probabilities of each of the two
      extinction routes and predict the most likely path of the subpopulations to
      extinction. We also suggest an effective three-state master equation for the
      probabilities to observe the coexistence state, the predator-free state, and the
      empty state.

PMID- 22463186
TI  - Crossover in growth law and violation of superuniversality in the random-field
      Ising model.
AB  - We study the nonconserved phase-ordering dynamics of the d=2,3 random-field Ising
      model, quenched to below the critical temperature. Motivated by the puzzling
      results of previous work in two and three dimensions, reporting a crossover from
      power-law to logarithmic growth, together with superuniversal behavior of the
      correlation function, we have undertaken a careful investigation of both the
      domain growth law and the autocorrelation function. Our main results are as
      follows: We confirm the crossover to asymptotic logarithmic behavior in the
      growth law, but, at variance with previous findings, we find the exponent in the
      preasymptotic power law to be disorder dependent, rather than being that of the
      pure system. Furthermore, we find that the autocorrelation function does not
      display superuniversal behavior. This restores consistency with previous results
      for the d=1 system, and fits nicely into the unifying scaling scheme we have
      recently proposed in the study of the random-bond Ising model.

PMID- 22463187
TI  - Magnetic properties and critical behavior of disordered Fe(1-x)Ru(x) alloys: a
      Monte Carlo approach.
AB  - We study the critical behavior of a quenched random-exchange Ising model with
      competing interactions on a bcc lattice. This model was introduced in the study
      of the magnetic behavior of Fe(1-x)Ru(x) alloys for ruthenium concentrations
      x=0%, x=4%, x=6%, and x=8%. Our study is carried out within a Monte Carlo
      approach, with the aid of a re-weighting multiple histogram technique. By means
      of a finite-size scaling analysis of several thermodynamic quantities, taking
      into account up to the leading irrelevant scaling field term, we find estimates
      of the critical exponents alpha, beta, gamma, and nu, and of the critical
      temperatures of the model. Our results for x=0% are in excellent agreement with
      those for the three-dimensional pure Ising model in the literature. We also show
      that our critical exponent estimates for the disordered cases are consistent with
      those reported for the transition line between paramagnetic and ferromagnetic
      phases of both randomly dilute and +/-J Ising models. We compare the behavior of
      the magnetization as a function of temperature with that obtained by Paduani and
      Branco (2008), qualitatively confirming the mean-field result. However, the
      comparison of the critical temperatures obtained in this work with experimental
      measurements suggest that the model (initially obtained in a mean-field approach)
      needs to be modified.

PMID- 22463188
TI  - Field theory of bicritical and tetracritical points. IV. Critical dynamics
      including reversible terms.
AB  - This article concludes a series of papers [Folk, Holovatch, and Moser, Phys. Rev.
      E 78, 041124 (2008); 78, 041125 (2008); 79, 031109 (2009)] where the tools of the
      field theoretical renormalization group were employed to explain and
      quantitatively describe different types of static and dynamic behavior in the
      vicinity of multicritical points. Here we give the complete two-loop calculation
      and analysis of the dynamic renormalization-group flow equations at the
      multicritical point in anisotropic antiferromagnets in an external magnetic
      field. We find that the time scales of the order parameters characterizing the
      parallel and perpendicular ordering with respect to the external field scale in
      the same way. This holds independent whether the Heisenberg fixed point or the
      biconical fixed point in statics is the stable one. The nonasymptotic analysis of
      the dynamic flow equations shows that due to cancellation effects the critical
      behavior is described, in distances from the critical point accessible to
      experiments, by the critical behavior qualitatively found in one-loop order.
      Although one may conclude from the effective dynamic exponents (taking almost
      their one-loop values) that weak scaling for the order parameter components is
      valid, the flow of the time-scale ratios is quite different, and they do not
      reach their asymptotic values.

PMID- 22463189
TI  - Thermal rounding exponent of the depinning transition of an elastic string in a
      random medium.
AB  - We study numerically thermal effects at the depinning transition of an elastic
      string driven in a two-dimensional uncorrelated disorder potential. The velocity
      of the string exactly at the sample critical force is shown to behave as
      V~T(psi), with psi the thermal rounding exponent. We show that the computed value
      of the thermal rounding exponent, psi=0.15, is robust and accounts for the
      different scaling properties of several observables both in the steady state and
      in the transient relaxation to the steady state. In particular, we show the
      compatibility of the thermal rounding exponent with the scaling properties of the
      steady-state structure factor, the universal short-time dynamics of the transient
      velocity at the sample critical force, and the velocity scaling function
      describing the joint dependence of the steady-state velocity on the external
      drive and temperature.

PMID- 22463190
TI  - Exact solution for statics and dynamics of maximal-entropy random walks on Cayley
      trees.
AB  - We provide analytical solutions for two types of random walk: generic random walk
      (GRW) and maximal-entropy random walk (MERW) on a Cayley tree with arbitrary
      branching number, root degree, and number of generations. For MERW, we obtain the
      stationary state given by the squared elements of the eigenvector associated with
      the largest eigenvalue lambda(0) of the adjacency matrix. We discuss the
      dynamics, depending on the second largest eigenvalue lambda(1), of the
      probability distribution approaching to the stationary state. We find different
      scaling of the relaxation time with the system size, which is generically shorter
      for MERW than for GRW. We also signal that depending on the initial conditions,
      there are relaxations associated with lower eigenvalues which are induced by
      symmetries of the tree. In general, we find that there are three regimes of a
      tree structure resulting in different statics and dynamics of MERW; these
      correspond to strongly, critically, and weakly branched roots.

PMID- 22463191
TI  - Time evolution of interacting vortices under overdamped motion.
AB  - A system of interacting vortices under overdamped motion, which has been commonly
      used in the literature to model flux-front penetration in disordered type-II
      superconductors, was recently related to a nonlinear Fokker-Planck equation,
      characteristic of nonextensive statistical mechanics, through an analysis of its
      stationary state. Herein, this connection is extended by means of a thorough
      analysis of the time evolution of this system. Numerical data from molecular
      dynamics simulations are presented for both position and velocity probability
      distributions P(x,t) and P(v(x),t), respectively; both distributions are well
      fitted by similar q-Gaussian distributions, with the same index q=0, for all
      times considered. Particularly, the evolution of the system occurs in such a way
      that P(x,t) presents a time behavior for its width, normalization, and second
      moment, in full agreement with the analytic solution of the nonlinear Fokker
      Planck equation. The present results provide further evidence that this system is
      deeply associated with nonextensive statistical mechanics.

PMID- 22463192
TI  - Inequivalence of time and ensemble averages in ergodic systems: exponential
      versus power-law relaxation in confinement.
AB  - Single-particle tracking has become a standard tool for the investigation of
      diffusive properties, especially in small systems such as biological cells.
      Usually the resulting time series are analyzed in terms of time averages over
      individual trajectories. Here we study confined normal as well as anomalous
      diffusion, modeled by fractional Brownian motion and the fractional Langevin
      equation, and show that even for such ergodic systems time-averaged quantities
      behave differently from their ensemble-averaged counterparts, irrespective of how
      long the measurement time becomes. Knowledge of the exact behavior of time
      averages is therefore fundamental for the proper physical interpretation of
      measured time series, in particular, for extraction of the relaxation time scale
      from data.

PMID- 22463193
TI  - Statistical theory of quasistationary states beyond the single water-bag case
      study.
AB  - An analytical solution for the out-of-equilibrium quasistationary states of the
      paradigmatic Hamiltonian mean field (HMF) model can be obtained from a maximum
      entropy principle. The theory has been so far tested with reference to a specific
      class of initial condition, the so called (single-level) water-bag type. In this
      paper a step forward is taken by considering an arbitrary number of overlapping
      water bags. The theory is benchmarked to direct microcanonical simulations
      performed for the case of a two-level water-bag. The comparison is shown to
      return an excellent agreement.

PMID- 22463194
TI  - Percolation in a kinetic opinion exchange model.
AB  - We study the percolation transition of the geometrical clusters in the square
      lattice LCCC model [a kinetic opinion exchange model introduced by Lallouache,
      Chakrabarti, Chakraborti, and Chakrabarti, Phys. Rev. E 82, 056112 (2010)] with
      the change in conviction and influencing parameter. The cluster is comprised of
      the adjacent sites having an opinion value greater than or equal to a prefixed
      threshold value of opinion (Omega). The transition point is different from that
      obtained for the transition of the order parameter (average opinion value) found
      by Lallouache et al. Although the transition point varies with the change in the
      threshold value of the opinion, the critical exponents for the percolation
      transition obtained from the data collapses of the maximum cluster size, the
      cluster size distribution, and the Binder cumulant remain the same. The exponents
      are also independent of the values of conviction and influencing parameters,
      indicating the robustness of this transition. The exponents do not match any
      other known percolation exponents (e.g., the static Ising, dynamic Ising, and
      standard percolation). This means that the LCCC model belongs to a separate
      universality class.

PMID- 22463195
TI  - Delayed uncoupled continuous-time random walks do not provide a model for the
      telegraph equation.
AB  - It has been alleged in several papers that the so-called delayed continuous-time
      random walks (DCTRWs) provide a model for the one-dimensional telegraph equation
      at microscopic level. This conclusion, being widespread now, is strange, since
      the telegraph equation describes phenomena with finite propagation speed, while
      the velocity of the motion of particles in the DCTRWs is infinite. In this paper
      we investigate the accuracy of the approximations to the DCTRWs provided by the
      telegraph equation. We show that the diffusion equation, being the correct limit
      of the DCTRWs, gives better approximations in L(2) norm to the DCTRWs than the
      telegraph equation. We conclude, therefore, that first, the DCTRWs do not provide
      any correct microscopic interpretation of the one-dimensional telegraph equation,
      and second, the kinetic (exact) model of the telegraph equation is different from
      the model based on the DCTRWs.

PMID- 22463196
TI  - Nonlinear wall pressure of a plunged granular column.
AB  - Scalings for slow drag and wall pressures in a plunged granular column are
      experimentally studied. A granular column is prepared in a cylindrical container
      and a spherical intruder is slowly plunged into it. Quasistatic drag force and
      pressures at the bottom and the side wall are measured simultaneously. Using the
      experimental data, we find scaling laws for drag force and wall pressures with
      some relevant length scales such as grains size and column dimensions. The
      obtained scaling laws elucidate the origin of nonlinear behavior of granular
      pressure. That is, the dimensionless column thickness is a key parameter to
      characterize the nonlinear granular pressure transmission.

PMID- 22463197
TI  - Unsteady non-Newtonian hydrodynamics in granular gases.
AB  - The temporal evolution of a dilute granular gas, both in a compressible flow
      (uniform longitudinal flow) and in an incompressible flow (uniform shear flow),
      is investigated by means of the direct simulation Monte Carlo method to solve the
      Boltzmann equation. Emphasis is laid on the identification of a first "kinetic"
      stage (where the physical properties are strongly dependent on the initial state)
      subsequently followed by an unsteady "hydrodynamic" stage (where the momentum
      fluxes are well-defined non-Newtonian functions of the rate of strain). The
      simulation data are seen to support this two-stage scenario. Furthermore, the
      rheological functions obtained from simulation are well described by an
      approximate analytical solution of a model kinetic equation.

PMID- 22463198
TI  - Evolution of pressure profiles during the discharge of a silo.
AB  - We report measurements of the pressure profile in the outlet plane of a
      discharging silo. We observe that, whatever the preparation of the granular
      system, a dynamic Janssen effect is at play: the apparent mass of the grains
      (i.e., the part of their mass sustained by the base) is significantly smaller
      than their actual mass because of the redirection of the weight to the lateral
      wall of the container. The pressure profiles reveal a significant decrease in
      pressure in the vicinity of the outlet as the system discharges, whereas the flow
      rate remains constant. The measurements are thus a direct experimental proof that
      the flow rates of granular material through an aperture are not controlled by the
      local stress conditions.

PMID- 22463199
TI  - Particle trajectories and size sorting above a rippled bed under standing water
      waves.
AB  - Particle trajectories and size sorting above an artificial rippled bed under
      standing surface waves are experimentally and theoretically studied. It is
      observed that fine particles may be trapped in a very thin region near the ripple
      crests. When the surface waves damp, fine particles concentrate on the top of
      ripple crests forming narrow strips, while coarse particles settle more uniformly
      along the rippled bed. Measurements of particle concentrations before their
      deposition confirm this size segregation. The present experimental results are
      explained with a theoretical approach.

PMID- 22463200
TI  - Bridging the rheology of granular flows in three regimes.
AB  - We investigate the rheology of granular materials via molecular dynamics
      simulations of homogeneous, simple shear flows of soft, frictional, noncohesive
      spheres. In agreement with previous results for frictionless particles, we
      observe three flow regimes existing in different domains of particle volume
      fraction and shear rate, with all stress data collapsing upon scaling by powers
      of the distance to the jamming point. Though this jamming point is a function of
      the interparticle friction coefficient, the relation between pressure and strain
      rate at this point is found to be independent of friction. We also propose a
      rheological model that blends the asymptotic relations in each regime to obtain a
      general description for these flows. Finally, we show that departure from
      inertial number scalings is a direct result of particle softness, with a
      dimensionless shear rate characterizing the transition.

PMID- 22463201
TI  - Two types of oscillation in unequally compartmentalized granular gases.
AB  - Granular oscillation in an unequally two-compartmentalized system is investigated
      experimentally, yielding two time periods: tau(LS) represents the time period for
      particles moving from the large to the small compartment, and tau(SL) is the time
      needed for movement in a reverse direction. We construct the phase diagram for
      the unequal system, discovering that there exist two different granular
      oscillation states. In the GOI state, tau(LS)>tau(SL) is observed, and (tau(LS)
      tau(SL)) increases as the difference between the two compartment widths is
      enlarged. In contrast, tau(LS)<tau(SL) is found in the GOII state, where the
      total number of particles is considerably lower than that in the GOI state. A
      flux model, accompanied by a proposed generalized granular temperature, is
      adopted to quantitatively calculate the observed time periods for both granular
      oscillation states. We find that the proposed temperature in each compartment is
      crucial in discriminating tau(LS) from tau(SL), and this is supported by the
      molecular dynamics analysis of mean kinetic energy of particles in a single
      compartment.

PMID- 22463202
TI  - Thermal segregation of intruders in the Fourier state of a granular gas.
AB  - A low density binary mixture of granular gases is considered within the Boltzmann
      kinetic theory. One component, the intruders, is taken to be dilute with respect
      to the other, and thermal segregation of the two species is described for a
      special solution to the Boltzmann equation. This solution has a macroscopic
      hydrodynamic representation with a constant temperature gradient and is referred
      to as the Fourier state. The thermal diffusion factor characterizing conditions
      for segregation is calculated without the usual restriction to Navier-Stokes
      hydrodynamics. Integral equations for the coefficients in this hydrodynamic
      description are calculated approximately within a Sonine polynomial expansion.
      Molecular dynamics simulations are reported, confirming the existence of this
      idealized Fourier state. Good agreement is found for the predicted and simulated
      thermal diffusion coefficient, while only qualitative agreement is found for the
      temperature ratio.

PMID- 22463203
TI  - Segregation of an intruder in a heated granular dense gas.
AB  - A recent segregation criterion [Phys. Rev. E 78, 020301(R) (2008)] based on the
      thermal diffusion factor Lambda of an intruder in a heated granular gas described
      by the inelastic Enskog equation is revisited. The sign of Lambda provides a
      criterion for the transition between the Brazil-nut effect (BNE) and the reverse
      Brazil-nut effect (RBNE). The present theory incorporates two extra ingredients
      not accounted for by the previous theoretical attempt. First, the theory is based
      upon the second Sonine approximation to the transport coefficients of the mass
      flux of the intruder. Second, the dependence of the temperature ratio (intruder
      temperature over that of the host granular gas) on the solid volume fraction is
      taken into account in the first and second Sonine approximations. In order to
      check the accuracy of the Sonine approximation considered, the Enskog equation is
      also numerically solved by means of the direct simulation Monte Carlo method to
      get the kinetic diffusion coefficient D(0). The comparison between theory and
      simulation shows that the second Sonine approximation to D(0) yields an
      improvement over the first Sonine approximation when the intruder is lighter than
      the gas particles in the range of large inelasticity. With respect to the form of
      the phase diagrams for the BNE-RBNE transition, the kinetic theory results for
      the factor Lambda indicate that while the form of these diagrams depends
      sensitively on the order of the Sonine approximation considered when gravity is
      absent, no significant differences between both Sonine solutions appear in the
      opposite limit (gravity dominates the thermal gradient). In the former case (no
      gravity), the first Sonine approximation overestimates both the RBNE region and
      the influence of dissipation on thermal diffusion segregation.

PMID- 22463204
TI  - Onset of irreversibility in cyclic shear of granular packings.
AB  - We investigate the onset of irreversibility in a dense granular medium subjected
      to cyclic shear in a split-bottom geometry. To probe the micro- and mesoscale, we
      image bead trajectories in three dimensions throughout a series of shear strain
      oscillations. Although beads lose and regain contact with neighbors during a
      cycle, the global topology of the contact network exhibits reversible properties
      for low oscillation amplitudes. With increasing reversal amplitude, a transition
      to an irreversible diffusive regime occurs.

PMID- 22463205
TI  - Effect of dynamic and static friction on an asymmetric granular piston.
AB  - We investigate the influence of dry friction on an asymmetric, granular piston of
      mass M, composed of two materials, undergoing inelastic collisions with bath
      particles of mass m. Numerical simulations of the Boltzmann-Lorentz equation
      reveal the existence of two scaling regimes depending on the friction strength.
      In the large friction limit, we introduce an exact model giving the asymptotic
      behavior of the Boltzmann-Lorentz equation. For small friction and for large mass
      ratio M/m, we derive a Fokker-Planck equation for which the exact solution is
      also obtained. Static friction attenuates the motor effect and results in a
      discontinuous velocity distribution.

PMID- 22463206
TI  - Formation of a disordered solid via a shock-induced transition in a dense
      particle suspension.
AB  - Shock wave propagation in multiphase media is typically dominated by the relative
      compressibility of the two components of the mixture. The difference in the
      compressibility of the components results in a shock-induced variation in the
      effective volume fraction of the suspension tending toward the random-close
      packing limit for the system, and a disordered solid can take form within the
      suspension. The present study uses a Hugoniot-based model to demonstrate this
      variation in the volume fraction of the solid phase as well as a simple hard
      sphere model to investigate the formation of disordered structures within
      uniaxially compressed model suspensions. Both models are discussed in terms of
      available experimental plate impact data in dense suspensions. Through
      coordination number statistics of the mesoscopic hard-sphere model, comparisons
      are made with the trends of the experimental pressure-volume fraction
      relationship to illustrate the role of these disordered structures in the bulk
      properties of the suspensions. A criterion for the dynamic stiffening of
      suspensions under high-rate dynamic loading is suggested as an analog to quasi
      static jamming based on the results of the simulations.

PMID- 22463207
TI  - X-ray photon correlation spectroscopy during homogenous shear flow.
AB  - We report x-ray photon correlation spectroscopy measurements of advective and
      diffusive dynamics in a dispersion of colloidal particles subjected to
      homogeneous shear flow in a rotating-disk shear cell. Intensity autocorrelation
      functions from scattering data collected using homodyne detection respond to the
      variation in velocity across the scattering volume when the scattering vector has
      a component parallel to the flow direction. Theoretical expressions for the
      impact of homogenous shear flow on the correlation function provide a
      quantitative prediction of the dependence of correlation functions on the
      scattering vector and shear rate. Under most circumstances, the applied shear
      deformation dominates the decay of the intensity correlation function. When
      scattering data are collected perpendicular to the flow direction, it is possible
      to measure the diffusive dynamics of the particles free from effects of the
      superimposed shear flow; however, this approach only works below some upper shear
      rate limit, beyond which data are affected either by shear effects (caused by the
      finite width of the detector) or by particle transit through the scattering
      volume.

PMID- 22463208
TI  - Stability and minimum size of colloidal clusters on a liquid-air interface.
AB  - A vertical force applied to each of two colloids, trapped at a liquid-air
      interface, induces their logarithmic pairwise attraction. I recently showed
      [Phys. Rev. E 79, 011407 (2009)] that in clusters of size R much larger than the
      capillary length lambda, the attraction changes to that of a power law and is
      much stronger due to a many-body effect, and I derived two equations that
      describe the equilibrium coarse-grained meniscus profile and colloid density in
      such clusters. In this paper, this theory is shown also to describe small
      clusters with R? lambda provided the number N of colloids therein is sufficiently
      large. An analytical solution for a small circular cluster with an arbitrary
      short-range power-law pairwise repulsion is found. The energy of a cluster is
      obtained as a function of its radius R and colloid number N. As in large
      clusters, the attraction force and energy universally scale with the distance L
      between colloids as L(-3) and L(-2), respectively, for any repulsion forces. The
      states of an equilibrium cluster, predicted by the theory, are shown to be stable
      with respect to small perturbations of the meniscus profile and colloid density.
      The minimum number of colloids in a circular cluster, which sustains the thermal
      motion, is estimated. For standard parameters, it can be very modest, e.g., in
      the range 20-200, which is in line with experimental findings on reversible
      clusterization on a liquid-air interface.

PMID- 22463209
TI  - Sudden collapse of a colloidal gel.
AB  - Metastable gels formed by weakly attractive colloidal particles display a
      distinctive two-stage time-dependent settling behavior under their own weight.
      Initially, a space-spanning network is formed that, for a characteristic time,
      which we define as the lag time tau(d), resists compaction. This solidlike
      behavior persists only for a limited time. Gels whose age t(w) is greater than
      tau(d) yield and suddenly collapse. We use a combination of confocal microscopy,
      rheology, and time-lapse video imaging to investigate both the process of sudden
      collapse and its microscopic origin in a refractive-index matched emulsion
      polymer system. We show that the height h of the gel in the early stages of
      collapse is well described by the surprisingly simple expression, h(tau)=h(0)
      Atau(3/2), with h(0) the initial height and tau=t(w)-tau(d) the time counted from
      the instant where the gel first yields. We propose that this unexpected result
      arises because the colloidal network progressively builds up internal stress as a
      consequence of localized rearrangement events, which leads ultimately to collapse
      as thermal equilibrium is reestablished.

PMID- 22463210
TI  - Direct visualization of three-dimensional crystallization behavior in microgels.
AB  - We use confocal microscopy to study the three-dimensional (3D) structure of
      colloidal crystals formed by poly(N-isopropylacrylamide)-co-(acrylic acid)
      microgels of diameter 1.0-1.5 MUm. The confocal images are tracked to locate
      particle positions in 3D, which are used to compute pair-correlation functions
      g(r), bond order parameters, and structure factors s(q). We find that the
      structure remains fcc for a range of charge, size, and concentration of the
      particles. When the particles are weakly attractive and are at low
      concentrations, polycrystalline solids result. In addition, owing to the
      compressibility of the colloids, the crystals display remarkable structural
      stability when subjected to external stress.

PMID- 22463211
TI  - Self-propelled Brownian spinning top: dynamics of a biaxial swimmer at low
      Reynolds numbers.
AB  - Recently the Brownian dynamics of self-propelled (active) rodlike particles was
      explored to model the motion of colloidal microswimmers, catalytically driven
      nanorods, and bacteria. Here we generalize this description to biaxial particles
      with arbitrary shape and derive the corresponding Langevin equation for a self
      propelled Brownian spinning top. The biaxial swimmer is exposed to a hydrodynamic
      Stokes friction force at low Reynolds numbers, to fluctuating random forces and
      torques as well as to an external and an internal (effective) force and torque.
      The latter quantities control its self-propulsion. Due to biaxiality and
      hydrodynamic translational-rotational coupling, the Langevin equation can only be
      solved numerically. In the special case of an orthotropic particle in the absence
      of external forces and torques, the noise-free (zero-temperature) trajectory is
      analytically found to be a circular helix. This trajectory is confirmed
      numerically to be more complex in the general case of an arbitrarily shaped
      particle under the influence of arbitrary forces and torques involving a
      transient irregular motion before ending up in a simple periodic motion. By
      contrast, if the external force vanishes, no transient regime is found, and the
      particle moves on a superhelical trajectory. For orthotropic particles, the noise
      averaged trajectory is a generalized concho-spiral. We furthermore study the
      reduction of the model to two spatial dimensions and classify the noise-free
      trajectories completely finding circles, straight lines with and without
      transients, as well as cycloids and arbitrary periodic trajectories.

PMID- 22463212
TI  - Multifractal analysis of the branch structure of diffusion-limited aggregates.
AB  - We examine the branch structure of radial diffusion-limited aggregation (DLA)
      clusters for evidence of multifractality. The lacunarity of DLA clusters is
      measured and the generalized dimensions D(q) of their mass distribution is
      estimated using the sandbox method. We find that the global n-fold symmetry of
      the aggregates can induce anomalous scaling behavior into these measurements.
      However, negating the effects of this symmetry, standard scaling is recovered.

PMID- 22463213
TI  - Characterization of the dynamics of glass-forming liquids from the properties of
      the potential energy landscape.
AB  - We develop a framework for understanding the difference between strong and
      fragile behavior in the dynamics of glass-forming liquids from the properties of
      the potential energy landscape. Our approach is based on a master equation
      description of the activated jump dynamics among the local minima of the
      potential energy (the so-called inherent structures) that characterize the
      potential energy landscape of the system. We study the dynamics of a small atomic
      cluster using this description as well as molecular dynamics simulations and
      demonstrate the usefulness of our approach for this system. Many of the
      remarkable features of the complex dynamics of glassy systems emerge from the
      activated dynamics in the potential energy landscape of the atomic cluster. The
      dynamics of the system exhibits typical characteristics of a strong supercooled
      liquid when the system is allowed to explore the full configuration space. This
      behavior arises because the dynamics is dominated by a few lowest-lying minima of
      the potential energy and the potential energy barriers between these minima. When
      the system is constrained to explore only a limited region of the potential
      energy landscape that excludes the basins of attraction of a few lowest-lying
      minima, the dynamics is found to exhibit the characteristics of a fragile liquid.

PMID- 22463214
TI  - Layering, freezing, and re-entrant melting of hard spheres in soft confinement.
AB  - Confinement can have a dramatic effect on the behavior of all sorts of
      particulate systems, and it therefore is an important phenomenon in many
      different areas of physics and technology. Here, we investigate the role played
      by the softness of the confining potential. Using grand canonical Monte Carlo
      simulations, we determine the phase diagram of three-dimensional hard spheres
      that in one dimension are constrained to a plane by a harmonic potential. The
      phase behavior depends strongly on the density and on the stiffness of the
      harmonic confinement. While we find the familiar sequence of confined hexagonal
      and square-symmetric packings, we do not observe any of the usual intervening
      ordered phases. Instead, the system phase separates under strong confinement, or
      forms a layered re-entrant liquid phase under weaker confinement. It is plausible
      that this behavior is due to the larger positional freedom in a soft confining
      potential and to the contribution that the confinement energy makes to the total
      free energy. The fact that specific structures can be induced or suppressed by
      simply changing the confinement conditions (e.g., in a dielectrophoretic trap) is
      important for applications that involve self-assembled structures of colloidal
      particles.

PMID- 22463215
TI  - Inhomogeneous shear flows in soft jammed materials with tunable attractive
      forces.
AB  - We perform molecular dynamics simulations to characterize the occurrence of
      inhomogeneous shear flows in soft jammed materials. We use rough walls to impose
      a simple shear flow and study the athermal motion of jammed assemblies of soft
      particles in two spatial dimensions, both for purely repulsive interactions and
      in the presence of an additional short-range attraction of varying strength. In
      steady state, pronounced flow inhomogeneities emerge for all systems when the
      shear rate becomes small. Deviations from linear flow are stronger in magnitude
      and become very long lived when the strength of the attraction increases, but
      differ from permanent shear bands. Flow inhomogeneities occur in a stress window
      bounded by the dynamic and static yield stress values. Attractive forces enhance
      the flow heterogeneities because they accelerate stress relaxation, thus
      effectively moving the system closer to the yield stress regime where
      inhomogeneities are most pronounced. The present scenario for understanding the
      effect of particle adhesion on shear localization, which is based on detailed
      molecular dynamics simulations with realistic particle interactions, differs
      qualitatively from previous qualitative explanations and ad hoc theoretical
      modeling.

PMID- 22463216
TI  - Treating inertia in passive microbead rheology.
AB  - The dynamic modulus G(*) of a viscoelastic medium is often measured by following
      the trajectory of a small bead subject to Brownian motion in a method called
      "passive microbead rheology." This equivalence between the positional
      autocorrelation function of the tracer bead and G(*) is assumed via the
      generalized Stokes-Einstein relation (GSER). However, inertia of both bead and
      medium are neglected in the GSER so that the analysis based on the GSER is not
      valid at high frequency where inertia is important. In this paper we show how to
      treat both contributions to inertia properly in one-bead passive microrheological
      analysis. A Maxwell fluid is studied as the simplest example of a viscoelastic
      fluid to resolve some apparent paradoxes of eliminating inertia. In the original
      GSER, the mean-square displacement (MSD) of the tracer bead does not satisfy the
      correct initial condition. If bead inertia is considered, the proper initial
      condition is realized, thereby indicating an importance of including inertia, but
      the MSD oscillates at a time regime smaller than the relaxation time of the
      fluid. This behavior is rather different from the original result of the GSER and
      what is observed. What is more, the discrepancy from the GSER result becomes
      worse with decreasing bead mass, and there is an anomalous gap between the MSD
      derived by naively taking the zero-mass limit in the equation of motion and the
      MSD for finite bead mass as indicated by McKinley et al. [J. Rheol. 53, 1487
      (2009)]. In this paper we show what is necessary to take the zero-mass limit of
      the bead safely and correctly without causing either the inertial oscillation or
      the anomalous gap, while obtaining the proper initial condition. The presence of
      a very small purely viscous element can be used to eliminate bead inertia safely
      once included in the GSER. We also show that if the medium contains relaxation
      times outside the window where the single-mode Maxwell behavior is observed, the
      oscillation can be attenuated inside the window. This attenuation is realized
      even in the absence of a purely viscous element. Finally, fluid inertia also
      affects the bead autocorrelation through the Basset force and the fluid dragged
      around with the bead. We show that the Basset force plays the same role as the
      purely viscous element in high-frequency regime, and the oscillation of MSD is
      suppressed if fluid density and bead density are comparable.

PMID- 22463217
TI  - Gap-size and capture-zone distributions in one-dimensional point-island
      nucleation and growth simulations: asymptotics and models.
AB  - The nucleation and growth of point islands during submonolayer deposition on a
      one-dimensional substrate is simulated for critical island size i=0,1,2,3. The
      small- and large-size asymptotics for the gap-size and capture-zone distributions
      (CZDs) are studied. Comparisons to theoretical predictions from fragmentation
      equation analyses are made, along with those from the recently proposed
      generalized Wigner surmise (GWS). We find that the simulation data can be fully
      understood in the framework provided by the fragmentation equations, while
      highlighting the theoretical areas that require further development. The GWS
      works well for the small-size CZD behavior, but completely fails to describe the
      large-size CZD asymptotics of the one-dimensional system.

PMID- 22463218
TI  - Grand-potential formulation for multicomponent phase transformations combined
      with thin-interface asymptotics of the double-obstacle potential.
AB  - In this paper, we describe the derivation of a model for the simulation of phase
      transformations in multicomponent real alloys starting from a grand-potential
      functional. We first point out the limitations of a phase-field model when
      evolution equations for the concentration and the phase-field variables are
      derived from a free energy functional. These limitations are mainly attributed to
      the contribution of the grand-chemical-potential excess to the interface energy.
      For a range of applications, the magnitude of this excess becomes large and its
      influence on interface profiles and dynamics is not negligible. The related
      constraint regarding the choice of the interface thickness limits the size of the
      domain that can be simulated and, hence, the effect of larger scales on
      microstructure evolution can not be observed. We propose a modification to the
      model in order to decouple the bulk and interface contributions. Following this,
      we perform the thin-interface asymptotic analysis of the phase-field model.
      Through this, we determine the thin-interface kinetic coefficient and the
      antitrapping current to remove the chemical potential jump at the interface. We
      limit our analysis to the Stefan condition at lowest order in epsilon (parameter
      related to the interface width) and apply results from previous literature that
      the corrections to the Stefan condition (surface diffusion and interface
      stretching) at higher orders are removed when antisymmetric interpolation
      functions are used for interpolating the grand-potential densities and the
      diffusion mobilities.

PMID- 22463219
TI  - Contact instabilities of anisotropic and inhomogeneous soft elastic films.
AB  - Anisotropy plays important roles in various biological phenomena such as adhesion
      of geckos and grasshoppers enabled by the attachment pods having hierarchical
      structures like thin longitudinal setae connected with threads mimicked by
      anisotropic films. We study the contact instability of a transversely isotropic
      thin elastic film when it comes in contact proximity of another surface. In the
      present study we investigate the contact stability of a thin incompressible
      transversely isotropic film by performing linear stability analysis. Based on the
      linear stability analysis, we show that an approaching contactor renders the film
      unstable. The critical wavelength of the instability is a function of the total
      film thickness and the ratio of the Young's modulus in the longitudinal direction
      and the shear modulus in the plane containing the longitudinal axis. We also
      analyze the stability of a thin gradient film that is elastically inhomogeneous
      across its thickness. Compared to a homogeneous elastic film, it becomes unstable
      with a longer wavelength when the film becomes softer in going from the surface
      to the substrate.

PMID- 22463220
TI  - Multisite models to determine the distribution of kink sites adjacent to low
      energy edges.
AB  - Kink sites play a critical role in crystal growth. The incorporation of a growth
      unit into a kink site (1) maintains the free energy of the edge constant and (2)
      creates another site with the same properties. These properties allow growth
      through successive incorporation events to proceed in a self-sustaining manner
      such that the equilibrium spacing between kinks is maintained on average.
      Traditionally the distributions of kink sites have been determined using a single
      site model whereby the probabilities of encountering a kink site adjacent to an
      edge and encountering a disturbance along an edge are assumed equivalent. In this
      paper, we develop multisite models that determine the probabilities of
      encountering kink sites; with the requirement that they obey both properties
      necessary for growth through successive self-sustaining incorporation events. The
      probabilities determined using the multisite models diverge significantly from
      the single-site model for edges with intermolecular interactions ?6k(b)T between
      successive molecules. The implications of these findings for the development of
      predictive crystal shape models and experimental analysis are discussed.

PMID- 22463221
TI  - Capillary-wave description of rapid directional solidification.
AB  - A recently introduced capillary-wave description of binary-alloy solidification
      is generalized to include the procedure of directional solidification. For a
      class of model systems a universal dispersion relation of the unstable eigenmodes
      of a planar steady-state solidification front is derived, which readjusts
      previously known stability considerations. We moreover establish a differential
      equation for oscillatory motions of a planar interface that offers a limit-cycle
      scenario for the formation of solute bands and, taking into account the Mullins
      Sekerka instability, of banded structures.

PMID- 22463222
TI  - Beyond the constraints underlying Kolmogorov-Johnson-Mehl-Avrami theory related
      to the growth laws.
AB  - The theory of Kolmogorov-Johnson-Mehl-Avrami for phase transition kinetics is
      subjected to severe limitations concerning the functional form of the growth law.
      This paper is devoted to sidestepping this drawback through the use of the
      correlation function approach. Moreover, we put forward an easy-to-handle
      formula, written in terms of the experimentally accessible actual extended volume
      fraction, which is found to match several types of growths. Computer simulations
      have been performed for corroborating the theoretical approach.

PMID- 22463223
TI  - Role of flexibility in the water repellency of water strider legs: theory and
      experiment.
AB  - Water striders enjoy an intriguing ability to stand and walk freely on water
      surfaces, which is mainly attributed to the superior water repellency of their
      slender legs. In previous theoretical analyses, the legs are usually treated as
      rigid beams and the results show that a tremendously deep dimple and a large
      supporting force can be achieved when the leg descends into water. In this paper,
      the effect of the flexibility of water strider legs on their water-repellent
      ability is investigated, both theoretically and experimentally. We analyze a
      hydrophobic and flexible leg pressing obliquely on water. The leg may undergo a
      large deformation and assume different geometric configurations. It is shown that
      the flexible leg can float easily on a water surface, inducing only a shallow
      water puddle and a moderate supporting force as observed in real water striders.
      When the long leg is sufficiently compliant, the water surface will never be
      pierced and the leg will never sink. The findings are experimentally testified by
      using flexible fibers to represent water strider legs pressing on water.

PMID- 22463224
TI  - Mean-field theory for coarsening faceted surfaces.
AB  - A mean-field theory is developed for the scale-invariant length distributions
      observed during the coarsening of generic one-dimensional faceted surfaces. This
      theory closely follows the Lifshitz-Slyozov-Wagner theory of Ostwald ripening in
      two-phase systems, but the mechanism of coarsening in faceted surfaces requires
      the addition of convolution terms recalling work on particle coalescence, and
      induces an unexpected coupling between the convolution and the rate of facet
      loss. As a generic framework, the theory concisely illustrates how the universal
      processes of facet removal and neighbor merger are moderated by the system
      specific mean-field velocity describing average rates of length change. For a
      simple, example facet dynamics associated with the directional solidification of
      a binary alloy, agreement between the predicted scaling state and that observed
      after direct numerical simulation of 40,000,000 facets is reasonable given the
      limiting assumption of noncorrelation between neighbors; relaxing this assumption
      is a clear path forward toward improved quantitative agreement with data in the
      future.

PMID- 22463225
TI  - Molecular theory of the tilting transition in smectic liquid crystals with weak
      layer contraction and diffused cone orientational distribution.
AB  - A molecular field theory of the smectic-A-smectic-C transition has been developed
      for smectics with a diffused cone orientational distribution of molecules
      (volcano-like distribution function) in the smectic-A phase and anomalously weak
      layer contraction in the smectic-C phase. Orientational order parameters and
      smectic layer spacing have been calculated numerically as functions of
      temperature and compared with the results obtained using a model with a standard
      Maier-Saupe-type distribution function that has been considered before. A
      molecular theory of the electroclinic effect in chiral smectics has also been
      developed using the recently proposed simple biaxial interaction potential. A
      comparison has been made between the absolute values and temperature variations
      of the electroclinic coefficient obtained using the volcano model, the model with
      Maier-Saupe-type distribution, and the orthodox cone model proposed by de Vries.
      It has been shown that the model with a conventional "sugar loaf" type
      orientational distribution function in the smectic-A phase is sufficient to
      describe the main properties of smectics with anomalously weak layer contraction.

PMID- 22463226
TI  - Mechanically tuned defect-mode multiplet for cholesteric photonic elastomers.
AB  - The multiplet structure of the optical defect modes generated within the bandgap
      are analyzed by a finite number of identical equispaced twist defects in axially
      elongated cholesteric elastomers. It is shown that n(0) defect modes induced by
      n(0) twist defects can be mechanically tuned. The transfer matrix is obtained and
      the defect frequencies when n(0)=1,2 are expressed in terms of twist angle,
      fractional shape anisotropy, and longitudinal deformation. For n(0)=2, the
      coupling between modes is analytically studied and it is shown that when the
      separation between defects is much larger than the line width, the defect modes
      do not interact and become degenerated.

PMID- 22463227
TI  - Anisotropy in the annihilation dynamics of umbilic defects in nematic liquid
      crystals.
AB  - Umbilic defects of strength s=+/-1 were induced in a nematic liquid crystal with
      negative dielectric anisotropy, confined to Hele-Shaw cells with homeotropic
      boundary conditions, and their annihilation dynamics followed experimentally. The
      speeds of individual defects of annihilating defect pairs with strengths of equal
      magnitude and opposite sign were determined as a function of several externally
      applied parameters, such as cell gap, electric field amplitude, frequency, and
      temperature. It was shown that annihilating defects do not approach each other at
      equal speeds, but that a speed anisotropy is observed, with the positive defect
      moving faster than the negative one. The defects move more slowly as the strength
      of the applied electric field or the cell gap is increased. The speed anisotropy
      is found to be essentially constant for varying external conditions which do not
      change the material properties of the liquid crystal material, i.e., confinement,
      electric field amplitude, or frequency. Only for applied conditions that change
      material properties, such as temperature changing viscosity, does the speed
      anisotropy vary. The annihilation dynamics was also simulated numerically giving
      good qualitative agreement with the experiments. Using insight gained from the
      simulations we interpret the defects' speed in terms of their overlap and the
      speed asymmetry as arising from backflow effects and anisotropy in the elastic
      constants.

PMID- 22463228
TI  - Photonic band gaps from a stack of right- and left-hand chiral photonic crystal
      layers.
AB  - In the present paper we investigated the optical properties of a stack of right-
      and left- hand chiral photonic crystal layers. The problem is solved by
      Ambartsumian's layer addition modified method. We investigated the reflection
      spectra peculiarities of this system and showed that in contrast to a single
      cholesteric liquid crystal (CLC) layer this system has multiple photonic band
      gaps (PBGs) (at light normal incidence). We showed that this system has unique
      polarization properties, particularly the eigenpolarizations (EPs) of the system
      are degenerated (i.e., the two EPs coincide) for an even number of layers and, in
      contrast to ordinary gyrotropic systems, the polarization plane rotation
      decreases if the system thickness is increased, the rotation sign depends on the
      first sublayer chirality sign, the system is very sensitive to the change of the
      sublayer number in the system, etc. We also investigated the influence of
      sublayer thicknesses, incidence angle, the sublayer local dielectric
      anisotropies, the sublayer helix pitches on the reflection peculiarities, and
      other optical parameters of the system.

PMID- 22463229
TI  - Critical behavior of director fluctuations in suspensions of ferroelectric
      nanoparticles in liquid crystals at the nematic to smectic-A phase transition.
AB  - By dynamic light scattering we studied the temperature dependence of scattered
      intensities and relaxation rates for pure twist and pure bend modes in a
      colloidal system of BaTiO(3) single domain nanoparticles and liquid crystal
      octylcyanobiphenyl (8CB) close to the nematic to smectic-A phase transition. From
      the experiments we obtained the critical exponents for the smectic correlation
      lengths, which in suspensions differ from the values for pure 8CB. The phase
      transition temperatures from isotropic to nematic phase (T(NI)) and from nematic
      to smectic-A phase (T(NA)) are both affected by the presence of the particles in
      two ways. The electric field around the ferroelectric particles increases the
      transition temperatures, whereas the disorder and probably also the excess of the
      surfactant cause a decrease of the transition temperatures compared to pure 8CB.
      The net effect is lower T(NI) and almost unchanged T(NA) in suspensions. After
      prolonged exposure to the external field the ferroelectric particles irreversibly
      aggregate, which results in the decrease of the internal electric field and,
      consequently, in the decrease of both transition temperatures.

PMID- 22463230
TI  - Nonlinear effective-medium theory of disordered spring networks.
AB  - Disordered soft materials, such as fibrous networks in biological contexts,
      exhibit a nonlinear elastic response. We study such nonlinear behavior with a
      minimal model for networks on lattice geometries with simple Hookian elements
      with disordered spring constant. By developing a mean-field approach to calculate
      the differential elastic bulk modulus for the macroscopic network response of
      such networks under large isotropic deformations, we provide insight into the
      origins of the strain stiffening and softening behavior of these systems. We find
      that the nonlinear mechanics depends only weakly on the lattice geometry and is
      governed by the average network connectivity. In particular, the nonlinear
      response is controlled by the isostatic connectivity, which depends strongly on
      the applied strain. Our predictions for the strain dependence of the isostatic
      point as well as the strain-dependent differential bulk modulus agree well with
      numerical results in both two and three dimensions. In addition, by using a
      mapping between the disordered network and a regular network with random forces,
      we calculate the nonaffine fluctuations of the deformation field and compare them
      to the numerical results. Finally, we discuss the limitations and implications of
      the developed theory.

PMID- 22463231
TI  - Slow knot formation by suppressed self-reptation in a collapsed polymer chain.
AB  - Chain-expansion processes from knotted globules have been measured for
      poly(methyl methacrylate) (PMMA) in the mixed solvent tert-butyl alcohol (TBA) +
      water (2.5 vol %) by static light scattering. The solution was quenched from the
      Theta temperature of 41.5  degrees C to 37.0  degrees C, aged there for a time
      period t(p,) and then returned rapidly to the Theta temperature. The chain
      expansion process was determined as a time evolution of the expansion factor
      alpha(2) after the temperature increase. The measurement was carried out by
      changing the aging time t(p) from 240 to 7200 min, and the molecular weight from
      M(w) = 4.0 * 10(6) to 1.5 * 10(7), by taking advantage of the extremely slow
      chain aggregation in the solution. The chain-expansion process obtained for M(w)
      = 1.22 * 10(7) became slow with increasing t(p), which revealed the knot
      formation in single globules. The characteristic time of the chain expansion from
      globules aged for t(p) = 7200 min was found to depend on the molecular weight as
      M(w)(2.7). This exponent, which is close to 3, demonstrated a disentanglement
      process due to self-reptation. The present data were compared with the previous
      data of the chain expansion from compact globules aged at 25.0  degrees C. The
      comparison made at M(w) = 1.22 * 10(7) and at the same values of t(p) revealed
      that the chain expansion from the globules aged at 25.0  degrees C was much
      faster than that from the globules at 37.0   degrees C, indicating a lower knot
      density in the more compact globules. It was conjectured that the knot formation
      due to self-reptation would be suppressed in a compact globule because an entire
      conformational change required by knot formation would become difficult to occur
      in the confined space of high segment concentration, particularly for a long
      polymer chain. The chain collapse of PMMA in the mixed solvent has been observed
      to occur extremely slowly at the later stage. This slow process was explained by
      the suppressed self-reptation.

PMID- 22463232
TI  - N-Body interactions in soft-sphere coarse-grained models of star polymers.
AB  - We consider the coarse-grained approach in which star polymers are mapped onto
      atoms located at the centers of the stars interacting by means of ultrasoft
      potentials. We generalize the Witten-Pincus formula to all n-body potentials: in
      the good-solvent regime all potentials show an ultrasoft logarithmic divergence
      when the relative distance of all n stars goes to zero, with coefficients that
      can be related to the partition-function exponents gamma(f).

PMID- 22463233
TI  - Electric-field-driven polymer entry into asymmetric nanoscale channels.
AB  - The electric-field-driven entry process of flexible charged polymers such as
      single-stranded DNA (ssDNA) into asymmetric nanoscale channels such as the alpha
      hemolysin protein channel is studied theoretically and using molecular dynamics
      simulations. Dependence of the height of the free-energy barrier on the polymer
      length, the strength of the applied electric field, and the channel entrance
      geometry is investigated. It is shown that the squeezing effect of the driving
      field on the polymer and the lateral confinement of the polymer before its entry
      to the channel crucially affect the barrier height and its dependence on the
      system parameters. The attempt frequency of the polymer for passing the channel
      is also discussed. Our theoretical and simulation results support each other and
      describe related data sets of polymer translocation experiments through the alpha
      hemolysin protein channel reasonably well.

PMID- 22463234
TI  - Force-induced breakdown of flexible polymerized membrane.
AB  - We consider the fracture of a free-standing two-dimensional (2D) elastic-brittle
      network to be used as protective coating subject to constant tensile stress
      applied on its rim. Using a molecular-dynamics simulation with a Langevin
      thermostat, we investigate the scission and recombination of bonds, and the
      formation of cracks in the 2D graphenelike hexagonal sheet for different pulling
      force f and temperature T. We find that bond rupture occurs almost always at the
      sheet periphery, and the first mean breakage time <tau> of bonds decays with
      membrane size as <tau> ?N(-beta), where beta~0.50+/-0.03 and N denotes the number
      of atoms in the membrane. The probability distribution of bond scission times t
      is given by a Poisson function W(t)?t(1/3)exp(-t/<tau>). The mean failure time
      <tau(r)> necessary to rip off the sheet declines with growing size N as a power
      law <tau(r)>?N(-phi(f)). We also find <tau(r)>?exp(DeltaU(0)/k(B)T), where the
      nucleation barrier for crack formation DeltaU(0)?f(-2), in agreement with
      Griffith's theory. <tau(r)> displays an Arrhenian dependence of <tau(r)> on
      temperature T. Our results indicate a rapid increase in crack spreading velocity
      with growing external tension f.

PMID- 22463235
TI  - Statistics and geometrical picture of ring polymer melts and solutions.
AB  - We present a detailed account of a recently proposed phenomenological theory for
      noncatenated ring polymer melts [Sakaue, Phys. Rev. Lett. 106, 167802 (2011)]. A
      basic assumption lies in the implementation of the noncatenation constraint via
      the effective excluded-volume effect, from which a geometrical picture of melts
      emerges. The result captures many of the salient features observed so far,
      including (i) the overall spatial size of rings, (ii) the coordinate number,
      i.e., the number of rings surrounding a given ring, (iii) the topological length
      scale as a function of the molecular weight, and (iv) the effect of the chain
      stiffness and concentration. We also suggest a geometrical interpretation of the
      topological length scale, which may shed some light on the entanglement concept
      in polymeric systems.

PMID- 22463236
TI  - Pressure-induced structural change of intermediate-range order in poly(4-methyl-1
      pentene) melt.
AB  - High-pressure in situ x-ray diffraction and specific-volume measurements on
      isotactic poly(4-methyl-1-pentene) melt have uncovered abrupt changes in the
      pressure dependence of microscopic structure as well as that of macroscopic
      density. The first sharp diffraction peak of the polymer melt, which is related
      to the intermediate-range order and is explained as resulting from the
      correlations between main chains, is suppressed at pressures less than 1 kbar.
      These changes in intermediate-range order show similarities to those seen in
      liquid-liquid or amorphous-amorphous transitions in simpler small molecule based
      systems, suggesting that this kind of phenomenon may occur in a wide range of
      materials.

PMID- 22463237
TI  - Mechanical behavior of linear amorphous polymers: comparison between molecular
      dynamics and finite-element simulations.
AB  - This paper studies the rheology of weakly entangled polymer melts and films in
      the glassy domain and near the rubbery domain using two different methods:
      molecular dynamics (MD) and finite element (FE) simulations. In a first step, the
      uniaxial mechanical behavior of a bulk polymer sample is studied by means of
      particle-based MD simulations. The results are in good agreement with
      experimental data, and mechanical properties may be computed from the
      simulations. This uniaxial mechanical behavior is then implemented in FE
      simulations using an elasto-viscoelasto-viscoplastic constitutive law in a
      continuum mechanics (CM) approach. In a second step, the mechanical response of a
      polymer film during an indentation test is modeled with the MD method and with
      the FE simulations using the same constitutive law. Good agreement is found
      between the MD and CM results. This work provides evidence in favor of using MD
      simulations to investigate the local physics of contact mechanics, since the
      volume elements studied are representative and thus contain enough information
      about the microstructure of the polymer model, while surface phenomena (adhesion
      and surface tension) are naturally included in the MD approach.

PMID- 22463238
TI  - Fluid dynamics of moving fish in a two-dimensional multiparticle collision
      dynamics model.
AB  - The fluid dynamics of animal locomotion, such as that of an undulating fish, are
      of great interest to both biologists and engineers. However, experimentally
      studying these fluid dynamics is difficult and time consuming. Model studies can
      be of great help because of their simpler and more detailed analysis. Their
      insights may guide empirical work. Particularly the recently introduced
      multiparticle collision dynamics method may be suitable for the study of moving
      organisms because it is computationally fast, simple to implement, and has a
      continuous representation of space. As regards the study of hydrodynamics of
      moving organisms, the method has only been applied at low Reynolds numbers (below
      120) for soft, permeable bodies, and static fishlike shapes. In the present paper
      we use it to study the hydrodynamics of an undulating fish at Reynolds numbers
      1100-1500, after confirming its performance for a moving insect wing at Reynolds
      number 75. We measure (1) drag, thrust, and lift forces, (2) swimming efficiency
      and spatial structure of the wake, and (3) distribution of forces along the fish
      body. We confirm the resemblance between the simulated undulating fish and
      empirical data. In contrast to theoretical predictions, our model shows that for
      steadily undulating fish, thrust is produced by the rear 2/3 of the body and that
      the slip ratio U/V (with U the forward swimming speed and V the rearward speed of
      the body wave) correlates negatively (instead of positively) with the actual
      Froude efficiency of swimming. Besides, we show that the common practice of
      modeling individuals while constraining their sideways acceleration causes them
      to resemble unconstrained fish with a higher tailbeat frequency.

PMID- 22463239
TI  - Enhanced bubble formation in looped short double-stranded DNA.
AB  - Recent experiments have shown the double-stranded (ds) DNAs readily bend and loop
      over the scale much shorter than their persistence length (50 nm). In an effort
      to unveil this seemingly surprising phenomenon, we study the emergence of bubbles
      in short ds DNA loops by simulating the breathing DNA model. We analyze the
      bubble size distributions and the melting curves for varying contour lengths,
      which are critically compared with those of linear DNA of the same lengths. We
      analytically evaluate the free energies associated with double-strand bending and
      single-strand bubble formation to explain the simulation data. It is found that
      in shorter looped DNA the bubbles are more easily initiated and formed to release
      the large bending energy, giving rise to melting at a lower temperature and a
      lower contour length.

PMID- 22463240
TI  - Macroscopic model of self-propelled bacteria swarming with regular reversals.
AB  - Periodic reversals in the direction of motion in systems of self-propelled rod
      shaped bacteria enable them to effectively resolve traffic jams formed during
      swarming and maximize the swarming rate of the colony. In this paper, a
      connection is established between a microscopic one-dimensional cell-based
      stochastic model of reversing nonoverlapping bacteria and a macroscopic nonlinear
      diffusion equation describing the dynamics of cellular density. Boltzmann-Matano
      analysis is used to determine the nonlinear diffusion equation corresponding to
      the specific reversal frequency. Stochastic dynamics averaged over an ensemble is
      shown to be in very good agreement with the numerical solutions of this nonlinear
      diffusion equation. Critical density p(0) is obtained such that nonlinear
      diffusion is dominated by the collisions between cells for the densities p>p(0).
      An analytical approximation of the pairwise collision time and semianalytical fit
      for the total jam time per reversal period are also obtained. It is shown that
      cell populations with high reversal frequencies are able to spread out
      effectively at high densities. If the cells rarely reverse, then they are able to
      spread out at lower densities but are less efficient at spreading out at higher
      densities.

PMID- 22463241
TI  - Duty ratio of cooperative molecular motors.
AB  - Molecular motors are found throughout the cells of the human body and have many
      different and important roles. These micromachines move along filament tracks and
      have the ability to convert chemical energy into mechanical work that powers
      cellular motility. Different types of motors are characterized by different duty
      ratios, which is the fraction of time that a motor is attached to its filament.
      In the case of myosin II (a nonprocessive molecular machine with a low duty
      ratio), cooperativity between several motors is essential to induce motion along
      its actin filament track. In this work we use statistical mechanical tools to
      calculate the duty ratio of cooperative molecular motors. The model suggests that
      the effective duty ratio of nonprocessive motors that work in cooperation is
      lower than the duty ratio of the individual motors. The origin of this effect is
      the elastic tension that develops in the filament which is relieved when motors
      detach from the track.

PMID- 22463242
TI  - Minimalistic behavioral rule derived from bacterial chemotaxis in a stochastic
      resonance setup.
AB  - Animals are able to cope with the noise, uncertainties, and complexity of the
      real world. Often even elementary living beings, equipped with very limited
      sensory organs, are able to reach regions favorable to their existence, using
      simple stochastic policies. In this paper we discuss a minimalistic stochastic
      behavioral rule, inspired from bacteria chemotaxis, which is able to increase the
      value of a specified evaluation function in a similar manner. In particular, we
      prove that, under opportune assumptions, the direction that is taken with maximum
      probability by an agent that follows this rule corresponds to the optimal
      direction. The rule does not require a specific agent dynamics, needs no memory
      for storing observed states, and works in generic n-dimensional spaces. It thus
      reveals itself interesting for the control of simple sensing robots as well.

PMID- 22463243
TI  - Modified permutation-entropy analysis of heartbeat dynamics.
AB  - Heart rate variability (HRV) contains important information about the modulation
      of the cardiovascular system. Various methods of nonlinear dynamics (e.g.,
      estimating Lyapunov exponents) and complexity measures (e.g., correlation
      dimension or entropies) have been applied to HRV analysis. Permutation entropy,
      which was proposed recently, has been widely used in many fields due to its
      conceptual and computational simplicity. It maps a time series onto a symbolic
      sequence of permutation ranks. The original permutation entropy assumes the time
      series under study has a continuous distribution, thus equal values are rare and
      can be ignored by ranking them according to their order of emergence, or broken
      by adding small random perturbations to ensure every symbol in a sequence is
      different. However, when the observed time series is digitized with lower
      resolution leading to a greater number of equal values, or the equalities
      represent certain characteristic sequential patterns of the system, it may not be
      rational to simply ignore or break them. In the present paper, a modified
      permutation entropy is proposed that, by mapping the equal value onto the same
      symbol (rank), allows for a more accurate characterization of system states. The
      application of the modified permutation entropy to the analysis of HRV is
      investigated using clinically collected data. Results show that modified
      permutation entropy can greatly improve the ability to distinguish the HRV
      signals under different physiological and pathological conditions. It can
      characterize the complexity of HRV more effectively than the original permutation
      entropy.

PMID- 22463244
TI  - Sampling rate of spatial stochastic processes with independent components in
      modeling random search paths.
AB  - Continuous-time modeling of random searches is designed to be robust to the
      sampling rate while the spatial model is required to be of rotation-invariant
      type, which is often computationally prohibitive. Such computational difficulty
      may be circumvented by employing a model with independent components. We
      demonstrate that its disadvantages in statistical properties are blurred under
      lower frequency. We propose a quantitative criterion for choice of the sampling
      rate at which a spatial model with independent components resembles a rotation
      invariant model. Our findings have the potential to assist the observer to employ
      simpler models in the continuous-time framework to avoid expensive computation
      required for statistical inference.

PMID- 22463245
TI  - Nonlinear-dynamics theory of up-down transitions in neocortical neural networks.
AB  - The neurons of the neocortex show ~1-Hz synchronized transitions between an
      active up state and a quiescent down state. The up-down state transitions are
      highly coherent over large sections of the cortex, yet they are accompanied by
      pronounced, incoherent noise. We propose a simple model for the up-down state
      oscillations that allows analysis by straightforward dynamical systems theory. An
      essential feature is a nonuniform network geometry composed of groups of
      excitatory and inhibitory neurons with strong coupling inside a group and weak
      coupling between groups. The enhanced deterministic noise of the up state appears
      as the natural result of the proximity of a partial synchronization transition.
      The synchronization transition takes place as a function of the long-range
      synaptic strength linking different groups of neurons.

PMID- 22463246
TI  - RNA fragment modeling with a nucleobase discrete-state model.
AB  - In this work we develop an approach for predicting the tertiary structures of RNA
      fragments by combining an RNA nucleobase discrete state (RNAnbds) model, a
      sequential Monte Carlo method, and a statistical potential. The RNAnbds model is
      designed for optimizing the configuration of nucleobases with respect to their
      preceding ones along the sequence and their spatial neighbors, in contrast to
      previous works that focus on RNA backbones. The tests of our approach with the
      fragments taken from a small RNA pseudoknot and a 23S ribosome RNA show that for
      short fragments (<10 nucleotides), the root mean square deviations (RMSDs)
      between the predicted and the experimental ones are generally smaller than 3 A;
      for slightly longer fragments (10-15 nucleotides), most RMSDs are smaller than 4
      A. The comparison of our method with another physics-based predictor with a
      testing set containing nine loops shows that ours is superior in both accuracy
      and efficiency. Our approach is useful in facilitating RNA three-dimensional
      structure prediction as well as loop modeling. It also holds the promise of
      providing insight into the structural ensembles of RNA loops.

PMID- 22463247
TI  - Response of traveling waves to transient inputs in neural fields.
AB  - We analyze the effects of transient stimulation on traveling waves in neural
      field equations. Neural fields are modeled as integro-differential equations
      whose convolution term represents the synaptic connections of a spatially
      extended neuronal network. The adjoint of the linearized wave equation can be
      used to identify how a particular input will shift the location of a traveling
      wave. This wave response function is analogous to the phase response curve of
      limit cycle oscillators. For traveling fronts in an excitatory network, the sign
      of the shift depends solely on the sign of the transient input. A complementary
      estimate of the effective shift is derived using an equation for the time
      dependent speed of the perturbed front. Traveling pulses are analyzed in an
      asymmetric lateral inhibitory network and they can be advanced or delayed,
      depending on the position of spatially localized transient inputs. We also
      develop bounds on the amplitude of transient input necessary to terminate
      traveling pulses, based on the global bifurcation structure of the neural field.

PMID- 22463248
TI  - Biophysical model of prokaryotic diversity in geothermal hot springs.
AB  - Recent studies of photosynthetic bacteria living in geothermal hot spring
      environments have revealed surprisingly complex ecosystems with an unexpected
      level of genetic diversity. One case of particular interest involves the
      distribution along hot spring thermal gradients of genetically distinct bacterial
      strains that differ in their preferred temperatures for reproduction and
      photosynthesis. In such systems, a single variable, temperature, defines the
      relevant environmental variation. In spite of this, each region along the thermal
      gradient exhibits multiple strains of photosynthetic bacteria adapted to several
      distinct thermal optima, rather than a single thermal strain adapted to the local
      environmental temperature. Here we analyze microbiology data from several
      ecological studies to show that the thermal distribution data exhibit several
      universal features independent of location and specific bacterial strain. These
      include the distribution of optimal temperatures of different thermal strains and
      the functional dependence of the net population density on temperature. We
      present a simple population dynamics model of these systems that is highly
      constrained by biophysical data and by physical features of the environment. This
      model can explain in detail the observed thermal population distributions, as
      well as certain features of population dynamics observed in laboratory studies of
      the same organisms.

PMID- 22463249
TI  - Collective motion of binary self-propelled particle mixtures.
AB  - In this study, we investigate the phenomenon of collective motion in binary
      mixtures of self-propelled particles. More precisely, we consider two particle
      species, each of which consisting of pointlike objects that propel with a
      velocity of constant magnitude. Within each species, the particles try to achieve
      polar alignment of their velocity vectors, whereas we analyze the cases of
      preferred polar, antiparallel, as well as perpendicular alignment between
      particles of different species. Our focus is on the effect that the interplay
      between the two species has on the threshold densities for the onset of
      collective motion and on the nature of the solutions above onset. For this
      purpose, we start from suitable Langevin equations in the particle picture, from
      which we derive mean field equations of the Fokker-Planck type and finally
      macroscopic continuum field equations. We perform particle simulations of the
      Langevin equations and linear stability analyses of the Fokker-Planck and
      macroscopic continuum equations, and we numerically solve the Fokker-Planck
      equations. Both spatially homogeneous and inhomogeneous solutions are
      investigated, where the latter correspond to stripelike flocks of collectively
      moving particles. In general, the interaction between the two species reduces the
      threshold density for the onset of collective motion of each species. However,
      this interaction also reduces the spatial organization in the stripelike flocks.
      The case that shows the most interesting behavior is the one of preferred
      perpendicular alignment between different species. There a competition between
      polar and truly nematic orientational ordering of the velocity vectors takes
      place within each particle species. Finally, depending on the alignment rule for
      particles of different species and within certain ranges of particle densities,
      identical and inverted spatial density profiles can be found for the two particle
      species. The system under investigation is confined to two spatial dimensions.

PMID- 22463250
TI  - Biopotential signals of breast cancer versus tumor types and proliferation
      stages.
AB  - Clinical studies have shown compelling data of elevated biopotential signals
      recorded noninvasively from the breasts of women with breast cancer. While these
      data are compelling and show a strong potential for use in the noninvasive early
      detection of breast cancer, there remains significant knowledge gaps which must
      be addressed before this technology can be routinely used for breast cancer
      detection. A diffusion-drift model is developed to study the spatial and temporal
      characteristics of the biopotential signals of breast tumors taking into account
      the morphology and cell division stages. The electric signals of the most common
      tumor types-papillary, compact, and comedo-are also considered. The largest
      biopotential signal is observed from the compact tumor, while the smallest signal
      is observed from the papillary type. The results also show an increase in the
      time duration of the generated biopotential signals when cancer cells start their
      transitions at different time instants. The spatial and temporal variations of
      the biopotential signals are correlated with the tumor pattern which can have
      important implications for breast cancer detection.

PMID- 22463251
TI  - Neural population densities shape network correlations.
AB  - The way sensory microcircuits manage cellular response correlations is a crucial
      question in understanding how such systems integrate external stimuli and encode
      information. Most sensory systems exhibit heterogeneities in terms of population
      sizes and features, which all impact their dynamics. This work addresses how
      correlations between the dynamics of neural ensembles depend on the relative size
      or density of excitatory and inhibitory populations. To do so, we study an
      apparently symmetric system of coupled stochastic differential equations that
      model the evolution of the populations' activities. Excitatory and inhibitory
      populations are connected by reciprocal recurrent connections, and both receive
      different stimuli exhibiting a certain level of correlation with each other. A
      stability analysis is performed, which reveals an intrinsic asymmetry in the
      distribution of the fixed points with respect to the threshold of the
      nonlinearities. Based on this, we show how the cross correlation between the
      population responses depends on the density of the inhibitory population, and
      that a specific ratio between both population sizes leads to a state of zero
      correlation. We show that this so-called asynchronous state subsists, despite the
      presence of stimulus correlation, and most importantly, that it occurs only in
      asymmetrical systems where one population outnumbers the other. Using linear
      approximations, we derive analytical expressions for the root of the cross
      correlation function and study how the asynchronous state is impacted by the
      model's parameters. This work suggests a possible explanation for why inhibitory
      cells outnumber excitatory cells in the visual system.

PMID- 22463252
TI  - Multiscale multifractal analysis of heart rate variability recordings with a
      large number of occurrences of arrhythmia.
AB  - Human heart rate variability, in the form of time series of intervals between
      heart beats, shows complex, fractal properties. Recently, it was demonstrated
      many times that the fractal properties vary from point to point along the series,
      leading to multifractality. In this paper, we concentrate not only on the fact
      that the human heart rate has multifractal properties but also that these
      properties depend on the time scale in which the multifractality is measured.
      This time scale is related to the frequency band of the signal. We find that
      human heart rate variability appears to be far more complex than hitherto
      reported in the studies using a fixed time scale. We introduce a method called
      multiscale multifractal analysis (MMA), which allows us to extend the description
      of heart rate variability to include the dependence on the magnitude of the
      variability and time scale (or frequency band). MMA is relatively immune to
      additive noise and nonstationarity, including the nonstationarity due to
      inclusions into the time series of events of a different dynamics (e.g.,
      arrhythmic events in sinus rhythm). The MMA method may provide new ways of
      measuring the nonlinearity of a signal, and it may help to develop new methods of
      medical diagnostics.

PMID- 22463253
TI  - Mechanical properties of epidermal cells of whole living roots of Arabidopsis
      thaliana: an atomic force microscopy study.
AB  - The knowledge of mechanical properties of root cell walls is vital to understand
      how these properties interact with relevant genetic and physiological processes
      to bring about growth. Expansion of cell walls is an essential component of
      growth, and the regulation of cell wall expansion is one of the ways in which the
      mechanics of growth is controlled, managed and directed. In this study, the
      inherent surface mechanical properties of living Arabidopsis thaliana whole-root
      epidermal cells were studied at the nanoscale using the technique of atomic force
      microscopy (AFM). A novel methodology was successfully developed to adapt AFM to
      live plant roots. Force-Indentation (F-I) experiments were conducted to
      investigate the mechanical properties along the length of the root. F-I curves
      for epidermal cells of roots were also generated by varying turgor pressure. The
      F-I curves displayed a variety of features due to the heterogeneity of the
      surface. Hysteresis is observed. Application of conventional models to living
      biological systems such as cell walls in nanometer regimes tends to increase
      error margins to a large extent. Hence information from the F-I curves were used
      in a preliminary semiquantitative analysis to infer material properties and
      calculate two parameters. The work done in the loading and unloading phases
      (hysteresis) of the force measurements were determined separately and were
      expressed in terms of "Index of Plasticity" (eta), which characterized the
      elasticity properties of roots as a viscoelastic response. Scaling approaches
      were used to find the ratio of hardness to reduced modulus (H/E(*)).

PMID- 22463254
TI  - Effect of duration of synaptic activity on spike rate of a Hodgkin-Huxley neuron
      with delayed feedback.
AB  - A recurrent loop consisting of a single Hodgkin-Huxley neuron influenced by a
      chemical excitatory delayed synaptic feedback is considered. We show that the
      behavior of the system depends on the duration of the activity of the synapse,
      which is determined by the activation and deactivation time constants of the
      synapse. For the fast synapses, those for which the effect of the synaptic
      activity is small compared to the period of firing, depending on the delay time,
      spiking with single and multiple interspike intervals is possible and the average
      firing rate can be smaller or larger than that of the open loop neuron. For slow
      synapses for which the synaptic time constants are of order of the period of the
      firing, the self-excitation increases the firing rate for all values of the delay
      time. We also show that for a chain consisting of few similar oscillators, if the
      synapses are chosen from different time constants, the system will follow the
      dynamics imposed by the fastest element, which is the oscillator that receives
      excitations via a slow synapse. The generalization of the results to other types
      of relaxation oscillators is discussed and the results are compared to those of
      the loops with inhibitory synapses as well as with gap junctions.

PMID- 22463255
TI  - Elastic response and length change of single DNA molecules induced by a
      combination of cisplatin and transplatin.
AB  - Magnetic tweezers were employed to investigate the interactions between DNA and
      cisplatin (transplatin). Cisplatin shortened DNA and reduced its persistence
      length more significantly than transplatin due to the formation of many more
      diadducts than those formed by transplatin. Interestingly, the presence of
      transplatin could enhance the ability of cisplatin in shortening DNA. An optimal
      concentration ratio of transplatin to cisplatin existed at which cisplatin showed
      the highest ability in shortening DNA. Moreover, abrupt length changes were also
      observed when DNA was treated with a mixture of cisplatin and transplatin at high
      concentrations. A model was proposed to qualitatively explain well these results.

PMID- 22463256
TI  - Facilitated diffusion on confined DNA.
AB  - In living cells, proteins combine three-dimensional bulk diffusion and one
      dimensional sliding along the DNA to reach a target faster. This process is known
      as facilitated diffusion and we investigate its dynamics in the physiologically
      relevant case of confined DNA. The confining geometry and DNA elasticity are key
      parameters: We find that facilitated diffusion is most efficient inside an
      isotropic volume and on a flexible polymer. By considering the typical copy
      numbers of proteins in vivo, we show that the speedup due to sliding becomes
      insensitive to fine tuning of parameters, rendering facilitated diffusion a
      robust mechanism to speed up intracellular diffusion-limited reactions. The
      parameter range we focus on is relevant for in vitro systems and for facilitated
      diffusion on yeast chromatin.

PMID- 22463257
TI  - Canards of mixed type in a neural burster.
AB  - Canards are solutions of slow-fast systems that spend long times near branches of
      repelling equilibria, periodic orbits, or higher-dimensional invariant sets.
      Here, we report on the observation of a new type of canard orbit, labeled a
      canard of mixed type. This canard orbit is a hybrid of the classical limit cycle
      canards, which spend long times near attracting and repelling branches of
      equilibria, and torus canards, which spend long times near attracting and
      repelling branches of periodic orbits. The canards of mixed type arise in a model
      of neural bursting activity of fold-fold cycle type, and, as other canard
      phenomena, separate different dynamic states.

PMID- 22463258
TI  - Classifying general nonlinear force laws in cell-based models via the continuum
      limit.
AB  - Although discrete cell-based frameworks are now commonly used to simulate a whole
      range of biological phenomena, it is typically not obvious how the numerous
      different types of model are related to one another, nor which one is most
      appropriate in a given context. Here we demonstrate how individual cell movement
      on the discrete scale modeled using nonlinear force laws can be described by
      nonlinear diffusion coefficients on the continuum scale. A general relationship
      between nonlinear force laws and their respective diffusion coefficients is
      derived in one spatial dimension and, subsequently, a range of particular
      examples is considered. For each case excellent agreement is observed between
      numerical solutions of the discrete and corresponding continuum models. Three
      case studies are considered in which we demonstrate how the derived nonlinear
      diffusion coefficients can be used to (a) relate different discrete models of
      cell behavior; (b) derive discrete, intercell force laws from previously posed
      diffusion coefficients, and (c) describe aggregative behavior in discrete
      simulations.

PMID- 22463260
TI  - Reproduction-time statistics and segregation patterns in growing populations.
AB  - Pattern formation in microbial colonies of competing strains under purely space
      limited population growth has recently attracted considerable research interest.
      We show that the reproduction time statistics of individuals has a significant
      impact on the sectoring patterns. Generalizing the standard Eden growth model, we
      introduce a simple one-parameter family of reproduction time distributions
      indexed by the variation coefficient delta?[0,1], which includes deterministic
      (delta=0) and memory-less exponential distribution (delta=1) as extreme cases. We
      present convincing numerical evidence and heuristic arguments that the
      generalized model is still in the Kardar-Parisi-Zhang (KPZ) universality class,
      and the changes in patterns are due to changing prefactors in the scaling
      relations, which we are able to predict quantitatively. With the example of
      Saccharomyces cerevisiae, we show that our approach using the variation
      coefficient also works for more realistic reproduction time distributions.

PMID- 22463259
TI  - Tank-treading of swollen erythrocytes in shear flows.
AB  - In this paper, we investigate computationally the oscillatory tank-treading
      motion of healthy swollen human erythrocytes (owing to lower than physiological
      plasma osmolarity) in shear flows with capillary number Ca=O(1) and small to
      moderate viscosity ratios 0.01<=lambda<=2.75. Swollen cells show similar shear
      flow dynamics with normal cells but with significantly higher inclination and
      tank-treading speed owing to the higher cell thickness. For a given viscosity
      ratio, as the flow rate increases, the steady-state erythrocyte length L (in the
      shear plane) increases logarithmically while its depth W (normal to the shear
      plane) decreases logarithmically; increase of the viscosity ratio results in
      lower cell deformation. The erythrocyte width S, which exists in the shear plane,
      is practically invariant in time, flow rate, and viscosity ratio and corresponds
      to a real cell thickness of about 2.5 MUm at physiological osmolarity (300 mO)
      and 3.4 MUm at an osmolarity of 217 mO. The erythrocyte inclination decreases as
      the flow rate increases or as the surrounding fluid viscosity decreases, owing to
      the increased inner rotational flow which tends to align the cell toward the flow
      direction. The ektacytometry deformation of swollen cells increases
      logarithmically with the shear stress but with a slower slope than that for
      normal cells owing mainly to the higher orientation of the more swollen cells. As
      the cell swelling increases, the tank-treading period decreases owing to the
      higher thickness of the actual cell which overcomes the opposite action of the
      reduced shape-memory effects (i.e., the more spherical-like erythrocyte's
      reference shape of shearing resistance). The local area incompressibility
      tensions from the lipid bilayer increase with the cell swelling and cause a
      higher cytoskeleton prestress; this increased prestress results in smaller, but
      still measurable, local area changes on the spectrin skeleton of the more swollen
      erythrocytes. Our work provides insight on the effects of clinical syndromes and
      biophysical processes associated with lowered plasma osmolarity (and thus higher
      cell swelling) such as inappropriate antidiuretic hormone secretion and diuretic
      therapy.

PMID- 22463261
TI  - Spatial dynamics in a predator-prey model with Beddington-DeAngelis functional
      response.
AB  - In this paper spatial dynamics of the Beddington-DeAngelis predator-prey model is
      investigated. We analyze the linear stability and obtain the condition of Turing
      instability of this model. Moreover, we deduce the amplitude equations and
      determine the stability of different patterns. In Turing space, we found that
      this model has coexistence of H(0) hexagon patterns and stripe patterns, H(pi)
      hexagon patterns, and H(0) hexagon patterns. To better describe the real
      ecosystem, we consider the ecosystem as an open system and take the environmental
      noise into account. It is found that noise can decrease the number of the
      patterns and make the patterns more regular. What is more, noise can induce two
      kinds of typical pattern transitions. One is from the H(pi) hexagon patterns to
      the regular stripe patterns, and the other is from the coexistence of H(0)
      hexagon patterns and stripe patterns to the regular stripe patterns. The obtained
      results enrich the finding in the Beddington-DeAngelis predator-prey model well.

PMID- 22463262
TI  - Effect of hydrogen bond anharmonicity on supersonic discrete Davydov soliton
      propagation.
AB  - We consider the propagation of energy along a protein chain in the Davydov
      approximation. We study the fully discrete Davydov equations including the
      anharmonic corrections in the hydrogen bond potential and find approximate
      variational solutions. We show analytically that for the harmonic interaction of
      the hydrogen bonds of the Davydov model the waves travel with velocities less
      than half the sound velocity for the relevant biological parameters. We find, for
      weak nonlinearity of the hydrogen bonds, two branches of soliton solutions. The
      first one gives a new type of strongly stable cusped discrete supersonic soliton.
      The second branch captures the main component of a more complicated breather
      solution compared to the one studied by Gaididei et al. and reproduces the
      Davydov soliton of the continuum limit. These results show the possibility of
      coherent protein chain deformation due to the anharmonicity of the hydrogen bond
      interactions. These supersonic waves are shown to provide a viable mechanism for
      energy transport in spite of the temperature influence in the soliton lifetime.

PMID- 22463263
TI  - Determination of the critical exponents for absorbing phase transitions in the
      conserved lattice gas model in three dimensions.
AB  - The critical exponents were measured for absorbing phase transitions in the
      conserved lattice gas (CLG) model on a simple cubic lattice. The correlation
      length exponent calculated from the dynamic exponent obtained by finite-size
      scaling and from the mean spreading distance was consistently found to be
      nu(?)=0.631+/-0.02, which yields a positive specific heat exponent alpha=2-dnu(?)
      on a pure system. The pure fixed point should, thus, be unstable if the Harris
      criterion established in equilibrium systems is applicable to the nonequilibrium
      absorbing phase transitions of the CLG model. However, this prediction is in
      contradiction with recent simulation results.

PMID- 22463264
TI  - Exact exponential function solution of the generalized Langevin equation for
      autocorrelation functions of many-body systems.
AB  - We show that an exact solution of the generalized Langevin equation (GLE) for the
      autocorrelations of a many-body classical system can be given in an exponential
      functionality (EF) form. As a consequence, the power spectrum of the correlation
      has a Lorentzian functionality, i.e., is represented by an infinite sum of
      Lorentzian functions corresponding to the eigenmodes of the considered
      correlation. By means of the simple derivation of the GLE by M. H. Lee [Phys.
      Rev. B 26, 2547 (1982)], we also show that, in practical cases of interest to
      experimental spectroscopies, possible approximations of the EF are related to a
      reduction of the relevant dynamical variables via a restriction of the dimensions
      of the orthogonalized space onto which the dynamics of the system is projected.

PMID- 22463265
TI  - Nonlocal viscosity kernel of mixtures.
AB  - In this Brief Report we investigate the multiscale hydrodynamical response of a
      liquid as a function of mixture composition. This is done via a series of
      molecular dynamics simulations in which the wave-vector-dependent viscosity
      kernel is computed for three mixtures, each with 7-15 different compositions. We
      observe that the viscosity kernel is dependent on composition for simple atomic
      mixtures for all the wave vectors studied here; however, for a molecular mixture
      the kernel is independent of composition for large wave vectors. The deviation
      from ideal mixing is also studied. Here it is shown that the Lorentz-Berthelot
      interaction rule follows ideal mixing surprisingly well for a large range of wave
      vectors, whereas for both the Kob-Andersen and molecular mixtures large
      deviations are found. Furthermore, for the molecular system the deviation is wave
      vector dependent such that there exists a characteristic correlation length scale
      at which the ideal mixing goes from underestimating to overestimating the
      viscosity.

PMID- 22463266
TI  - Effect on information transfer of synaptic pruning driven by spike-timing
      dependent plasticity.
AB  - Spike-timing-dependent plasticity (STDP) is an important driving force of self
      organization in neural systems. With properly chosen input signals, STDP can
      yield a synaptic pruning process, whose functional role needs to be further
      investigated. We explore this issue from an information theoretic standpoint.
      Temporally correlated stimuli are introduced to neurons of an input layer. Then
      synapses on the dendrite, and thus the receptive field, of an output neuron are
      refined by STDP. The mutual information between input and output spike trains is
      calculated with the context tree method. The results show that synapse removal
      can enhance information transfer, i.e., that "less can be more" under certain
      constraints that stress the balance between potentiation and depression dictated
      by the parameters of the STDP rule, as well as the temporal scale of the input
      correlation.

PMID- 22463267
TI  - Comment on "Length-dependent translation of messenger RNA by ribosomes".
AB  - In a recent paper by Valleriani et al. [Phys. Rev. E 83, 042903 (2011)], a simple
      model for the translation of messenger RNA (mRNA) is presented. Using this model,
      the protein translational ratio r, defined as the ratio of protein translation
      rate omega(tl) from mRNA to protein degradation rate omega(p), is obtained. The
      key point in obtaining the translational ratio r is to get the protein
      translation rate omega(tl). In Valleriani et al.'s paper, omega(tl) is obtained
      as the mean value of the measured translation rate, which is the ratio of the
      synthesized protein number to the mRNA lifetime. However, in experiments,
      different methods might be used to obtain the value of omega(tl). Therefore, to
      apply Valleriani et al.'s model to more general experiments, in this Comment
      three methods to obtain the translation rate omega(tl), and consequently the
      translational ratio r, are presented. Based on one of the methods which might be
      employed in most of the experiments, we find that the translational ratio r
      decays exponentially with mRNA length in prokaryotic cells, and decays
      reciprocally with mRNA length in eukaryotic cells. This result is slight
      different from that which was obtained in Valleriani et al.'s paper.

PMID- 22463268
TI  - Successful attack on permutation-parity-machine-based neural cryptography.
AB  - An algorithm is presented which implements a probabilistic attack on the key
      exchange protocol based on permutation parity machines. Instead of imitating the
      synchronization of the communicating partners, the strategy consists of a Monte
      Carlo method to sample the space of possible weights during inner rounds and an
      analytic approach to convey the extracted information from one outer round to the
      next one. The results show that the protocol under attack fails to synchronize
      faster than an eavesdropper using this algorithm.

PMID- 22463269
TI  - Breakup of small aggregates driven by turbulent hydrodynamical stress.
AB  - The breakup of small solid aggregates in homogeneous and isotropic turbulence is
      studied theoretically and by using direct numerical simulations at high Reynolds
      number, Relambda =/~ 400. We show that turbulent fluctuations of the hydrodynamic
      stress along the aggregate trajectory play a key role in determining the
      aggregate mass distribution function. The differences between turbulent and
      laminar flows are discussed. A definition of the fragmentation rate is proposed
      in terms of the typical frequency at which the hydrodynamic stress becomes
      sufficiently high to cause breakup along each Lagrangian path. We also define an
      Eulerian proxy of the real fragmentation rate, based on the joint statistics of
      the stress and its time derivative, which should be easier to measure in any
      experimental setup. Both our Eulerian and Lagrangian formulations define a clear
      procedure for the computation of the mass distribution function due to
      fragmentation. Contrary, previous estimates based only on single point statistics
      of the hydrodynamic stress exhibit some deficiencies. These are discussed by
      investigating the evolution of an ensemble of aggregates undergoing breakup and
      aggregation.

PMID- 22463270
TI  - Hydrodynamics of fractal continuum flow.
AB  - A model of fractal continuum flow employing local fractional differential
      operators is suggested. The generalizations of the Green-Gauss divergence and
      Reynolds transport theorems for a fractal continuum are suggested. The
      fundamental conservation laws and hydrodynamic equations for an anisotropic
      fractal continuum flow are derived. Some physical implications of the long-range
      correlations in the fractal continuum flow are briefly discussed. It is
      noteworthy to point out that the fractal (quasi)metric defined in this paper
      implies that the flow of an isotropic fractal continuum obeying the Mandelbrot
      rule of thumb for intersection is governed by conventional hydrodynamic
      equations.

PMID- 22463271
TI  - Experimental scaling law for the subcritical transition to turbulence in plane
      Poiseuille flow.
AB  - We present an experimental study of the transition to turbulence in a plane
      Poiseuille flow. Using a well-controlled perturbation, we analyze the flow by
      using extensive particle image velocimetry and flow visualization (using laser
      induced fluorescence) measurements, and use the deformation of the mean velocity
      profile as a criterion to characterize the state of the flow. From a large
      parametric study, four different states are defined, depending on the values of
      the Reynolds number and the amplitude of the perturbation. We discuss the role of
      coherent structures, such as hairpin vortices, in the transition. We find that
      the minimal amplitude of the perturbation triggering transition scales
      asymptotically as Re(-1).

PMID- 22463272
TI  - Spectrally peaked electron beams produced via surface guiding and acceleration in
      femtosecond laser-solid interactions.
AB  - Highly collimated MeV electron beam guiding has been observed along the target
      surface following the interaction of bulk target irradiation by femtosecond laser
      pulses at relativistic intensities. The beam quality is shown to depend
      critically on the laser contrast: With a ns prepulse, the generated electron beam
      is well concentrated and intense, while a high laser contrast produces divergent
      electron beams. In the case of large preplasma scale lengths, tunable guiding and
      acceleration of the target surface electrons is achieved by changing the laser
      incident angle. By expanding the preplasma scale length to several hundred
      micrometers, we obtained MeV spectrum-peaked electron beams with a 100 pC per
      laser pulse and divergence angles of only 3 degrees . This technique suggests a
      stable method of injection of elections into a variety of accelerator designs.

PMID- 22463273
TI  - Bias in generation of random graphs.
AB  - We study the statistical properties of the generation of random graphs according
      to the configuration model, in which one assigns randomly degrees to nodes. This
      model is often used, for example, for the scale-free degree distribution ~d(
      gamma). For the efficient variant, where nonfeasible edges are rejected and the
      construction of a graph continues, there exists a bias, which we calculate
      explicitly for a small sample ensemble. We find that this bias does not disappear
      with growing system size. This becomes visible, for example, also for scale-free
      graphs when measuring quantities such as the graph diameter. Hence the efficient
      generation of general scale-free graphs with a very broad distribution (gamma <
      2) remains an open problem.

PMID- 22463274
TI  - Homogeneous assumption and the logistic behavior of information propagation.
AB  - Many models of disease and rumor-spreading phenomena average the behavior of
      individuals in a population in order to obtain a coarse description of expected
      system behavior. For these types of models, we determine how close the coarse
      approximation is to its corresponding agent-based system. These findings lead to
      a general result on the logistic behavior of information propagation for networks
      on both connected graphs with doubly stochastic edge weights, and connected
      graphs with symmetric edge weights. Moreover, we discuss the appropriateness of
      the discrete logistic approximation for a few example heterogeneous graph
      topologies.

PMID- 22463275
TI  - Time-scale and noise optimality in self-organized critical adaptive networks.
AB  - Recent studies have shown that adaptive networks driven by simple local rules can
      organize into "critical" global steady states, providing another framework for
      self-organized criticality (SOC). We focus on the important convergence to
      criticality and show that noise and time-scale optimality are reached at finite
      values. This is in sharp contrast to the previously believed optimal zero noise
      and infinite time-scale separation case. Furthermore, we discover a noise-induced
      phase transition for the breakdown of SOC. We also investigate each of these
      three effects separately by developing models that reveal three generically low
      dimensional dynamical behaviors: time-scale resonance, a simplified version of
      stochastic resonance, which we call steady-state stochastic resonance, and noise
      induced phase transitions.

PMID- 22463276
TI  - Conditional strategies and the evolution of cooperation in spatial public goods
      games.
AB  - The fact that individuals will most likely behave differently in different
      situations begets the introduction of conditional strategies. Inspired by this,
      we study the evolution of cooperation in the spatial public goods game, where,
      besides unconditional cooperators and defectors, also different types of
      conditional cooperators compete for space. Conditional cooperators will
      contribute to the public good only if other players within the group are likely
      to cooperate as well but will withhold their contribution otherwise. Depending on
      the number of other cooperators that are required to elicit cooperation of a
      conditional cooperator, the latter can be classified in as many types as there
      are players within each group. We find that the most cautious cooperators, who
      require all other players within a group to be conditional cooperators, are the
      undisputed victors of the evolutionary process, even at very low synergy factors.
      We show that the remarkable promotion of cooperation is due primarily to the
      spontaneous emergence of quarantining of defectors, who become surrounded by
      conditional cooperators and are forced into isolated convex "bubbles" from which
      they are unable to exploit the public good. This phenomenon can be observed only
      in structured populations, thus adding to the relevance of pattern formation for
      the successful evolution of cooperation.

PMID- 22463277
TI  - Electron transfer reactions in condensed phase: effect of reversibility.
AB  - We propose a generalized one-dimensional kinetic equation for multidimensional
      reversible electron transfer (ET) reaction with a nonequilibrium situation as the
      initial condition. The rate constant for the forward reversible ET reaction
      obtained here consists of the rate for the corresponding irreversible ET
      reaction, and an extra term due to reversibility of the ET process which includes
      the rates of diffusion dynamics in the reactant and product wells. In order to
      understand the effect of reversibility, we consider back ET reaction in a system
      consisting of an electron donor-acceptor pair in a solvent modeled through low
      frequency solvent collective coordinates (multidimensional) characterized by the
      orientational polarization and slowly relaxing one-dimensional vibrational mode.
      We propose here a new generalized polarization energy functional corresponding to
      the extension of the continuum version for the same, which has opened up the
      possibility of inclusion of molecular nature of the solvent into the solvent
      reorganization energy. We then derive an exact expression for the ET rate for
      this model system. The numerical results calculated by using the proposed one
      dimensional approach are shown to be in good agreement with the available
      experimental results. Non-Marcus free energy gap dependence of the rates observed
      here for the reversible and irreversible ET reactions are very close to each
      other in the barrierless region, while for other situations, the rate for the
      former process is found to be less than the latter. The extra term, which makes
      the difference between the rate constants for irreversible and reversible ET
      reactions, is found to be contributed by the diffusion dynamics from both
      reactant and product wells but the dominating contribution is provided mainly by
      the product well.

PMID- 22463278
TI  - Accuracy of mean-field theory for dynamics on real-world networks.
AB  - Mean-field analysis is an important tool for understanding dynamics on complex
      networks. However, surprisingly little attention has been paid to the question of
      whether mean-field predictions are accurate, and this is particularly true for
      real-world networks with clustering and modular structure. In this paper, we
      compare mean-field predictions to numerical simulation results for dynamical
      processes running on 21 real-world networks and demonstrate that the accuracy of
      such theory depends not only on the mean degree of the networks but also on the
      mean first-neighbor degree. We show that mean-field theory can give
      (unexpectedly) accurate results for certain dynamics on disassortative real-world
      networks even when the mean degree is as low as 4.

PMID- 22463279
TI  - Temporal node centrality in complex networks.
AB  - Many networks are dynamic in that their topology changes rapidly--on the same
      time scale as the communications of interest between network nodes. Examples are
      the human contact networks involved in the transmission of disease, ad hoc radio
      networks between moving vehicles, and the transactions between principals in a
      market. While we have good models of static networks, so far these have been
      lacking for the dynamic case. In this paper we present a simple but powerful
      model, the time-ordered graph, which reduces a dynamic network to a static
      network with directed flows. This enables us to extend network properties such as
      vertex degree, closeness, and betweenness centrality metrics in a very natural
      way to the dynamic case. We then demonstrate how our model applies to a number of
      interesting edge cases, such as where the network connectivity depends on a small
      number of highly mobile vertices or edges, and show that our centrality
      definition allows us to track the evolution of connectivity. Finally we apply our
      model and techniques to two real-world dynamic graphs of human contact networks
      and then discuss the implication of temporal centrality metrics in the real
      world.

PMID- 22463280
TI  - Structural preferential attachment: stochastic process for the growth of scale
      free, modular, and self-similar systems.
AB  - Many complex systems have been shown to share universal properties of
      organization, such as scale independence, modularity, and self-similarity. We
      borrow tools from statistical physics in order to study structural preferential
      attachment (SPA), a recently proposed growth principle for the emergence of the
      aforementioned properties. We study the corresponding stochastic process in terms
      of its time evolution, its asymptotic behavior, and the scaling properties of its
      statistical steady state. Moreover, approximations are introduced to facilitate
      the modeling of real systems, mainly complex networks, using SPA. Finally, we
      investigate a particular behavior observed in the stochastic process, the peloton
      dynamics, and show how it predicts some features of real growing systems using
      prose samples as an example.

PMID- 22463281
TI  - Closed benchmarks for network community structure characterization.
AB  - Characterizing the community structure of complex networks is a key challenge in
      many scientific fields. Very diverse algorithms and methods have been proposed to
      this end, many working reasonably well in specific situations. However, no
      consensus has emerged on which of these methods is the best to use in practice.
      In part, this is due to the fact that testing their performance requires the
      generation of a comprehensive, standard set of synthetic benchmarks, a goal not
      yet fully achieved. Here, we present a type of benchmark that we call "closed,"
      in which an initial network of known community structure is progressively
      converted into a second network whose communities are also known. This approach
      differs from all previously published ones, in which networks evolve toward
      randomness. The use of this type of benchmark allows us to monitor the
      transformation of the community structure of a network. Moreover, we can predict
      the optimal behavior of the variation of information, a measure of the quality of
      the partitions obtained, at any moment of the process. This enables us in many
      cases to determine the best partition among those suggested by different
      algorithms. Also, since any network can be used as a starting point, extensive
      studies and comparisons can be performed using a heterogeneous set of structures,
      including random ones. These properties make our benchmarks a general standard
      for comparing community detection algorithms.

PMID- 22463283
TI  - Crack in the frictional interface as a solitary wave.
AB  - We introduce and investigate a multiscale model for the propagation of rupture
      fronts in friction. Taking advantage of the correlation length for the motion of
      individual contacts in elastic theory, we introduce collective contacts which can
      be characterized by a master equation approach. The problem of the dynamics of a
      chain of those effective contacts under stress is studied. We show that it can be
      reduced to an analog of the Frenkel-Kontorova model. In some limits this allows
      us to derive analytical solutions for kinks describing the rupture fronts.
      Numerical simulations are used to study more complex cases.

PMID- 22463282
TI  - Cascading dynamics on random networks: crossover in phase transition.
AB  - In a complex network, random initial attacks or failures can trigger subsequent
      failures in a cascading manner, which is effectively a phase transition. Recent
      works have demonstrated that in networks with interdependent links so that the
      failure of one node causes the immediate failures of all nodes connected to it by
      such links, both first- and second-order phase transitions can arise. Moreover,
      there is a crossover between the two types of transitions at a critical system
      parameter value. We demonstrate that these phenomena can occur in the more
      general setting where no interdependent links are present. A heuristic theory is
      derived to estimate the crossover and phase-transition points, and a remarkable
      agreement with numerics is obtained.

PMID- 22463284
TI  - Reciprocal interactions out of congestion-free adaptive networks.
AB  - In this paper we study the jamming transition in complex adaptive networks. We
      introduce an adaptation mechanism that modifies the weight of the communication
      channels in order to delay the congestion onset. Adaptivity takes place locally
      as it is driven by each node of the network. Surprisingly, regardless of the
      structural properties of the backbone topology, e.g., its degree distribution,
      the adaptive network can reach optimal functioning provided it allows a
      reciprocal distribution of the weights. Under this condition, the optimal
      functioning is achieved through an extensive network reshaping ending up in a
      highly reciprocal weighted network whose critical onset of congestion is delayed
      up to its maximum possible value. We also show that, for a given network, the
      reciprocal weighting obtained from adaptation produce optimal static
      configurations.

PMID- 22463285
TI  - Exact calculations of first-passage quantities on recursive networks.
AB  - We present general methods to exactly calculate mean first-passage quantities on
      self-similar networks defined recursively. In particular, we calculate the mean
      first-passage time and the splitting probabilities associated to a source and one
      or several targets; averaged quantities over a given set of sources (e.g., same
      connectivity nodes) are also derived. The exact estimate of such quantities
      highlights the dependency of first-passage processes with respect to the source
      target distance, which has recently revealed to be a key parameter in
      characterizing transport in complex media. We explicitly perform calculations for
      different classes of recursive networks [finitely ramified fractals, scale-free
      (trans)fractals, nonfractals, mixtures between fractals and nonfractals,
      nondecimable hierarchical graphs] of arbitrary size. Our approach unifies and
      significantly extends the available results in the field.

PMID- 22463286
TI  - Degree distribution and scaling in the connecting-nearest-neighbors model.
AB  - We present a detailed analysis of the connecting-nearest-neighbors model by
      Vazquez [Phys. Rev. E 67, 056104 (2003)]. We show that the degree distribution
      follows a power law, but the scaling exponent can vary with the parameter
      setting. Moreover, the correspondence of the growing version of the connecting
      nearest-neighbors model to the particular random walk model and recursive search
      model is established.

PMID- 22463287
TI  - Optimizing controllability of complex networks by minimum structural
      perturbations.
AB  - To drive a large, complex, networked dynamical system toward some desired state
      using as few external signals as possible is a fundamental issue in the emerging
      field of controlling complex networks. Optimal control is referred to the
      situation where such a network can be fully controlled using only one driving
      signal. We propose a general approach to optimizing the controllability of
      complex networks by judiciously perturbing the network structure. The principle
      of our perturbation method is validated theoretically and demonstrated
      numerically for homogeneous and heterogeneous random networks and for different
      types of real networks as well. The applicability of our method is discussed in
      terms of the relative costs of establishing links and imposing external
      controllers. Besides the practical usage of our approach, its implementation
      elucidates, interestingly, the intricate relationship between certain structural
      properties of the network and its controllability.

PMID- 22463288
TI  - Absence of influential spreaders in rumor dynamics.
AB  - Recent research [Kitsak, Gallos, Havlin, Liljeros, Muchnik, Stanley, and Makse,
      Nature Physics 6, 888 (2010)] has suggested that coreness, and not degree,
      constitutes a better topological descriptor to identify influential spreaders in
      complex networks. This hypothesis has been verified in the context of disease
      spreading. Here, we instead focus on rumor spreading models, which are more
      suited for social contagion and information propagation. To this end, we perform
      extensive computer simulations on top of several real-world networks and find
      opposite results. Namely, we show that the spreading capabilities of the nodes do
      not depend on their k-core index, which instead determines whether or not a given
      node prevents the diffusion of a rumor to a system-wide scale. Our findings are
      relevant both for sociological studies of contagious dynamics and for the design
      of efficient commercial viral processes.

PMID- 22463289
TI  - Vector bright soliton behaviors associated with negative coherent coupling.
AB  - With the introduction of an auxiliary function, a genuine bilinear system (in
      contrast to the published trilinear forms) is obtained for the two-coupled
      nonlinear Schrodinger equations with negative coherent coupling in the optical
      fiber communications. With symbolic computation, degenerate and nondegenerate
      vector solitons are derived associated with the corresponding phase-parameter
      constraints. In virtue of asymptotic analysis and graphical simulation, vector
      solitons of the single-hump, double-hump, or flat-top profiles are displayed, and
      the collision mechanisms of such vector solitons are revealed as well; namely,
      the collisions among degenerate solitons and among nondegenerate solitons are
      both elastic. The only possible inelastic collision, the collision in the
      degenerate-nondegenerate case, is pointed out, where a degenerate soliton
      interacts with a nondegenerate one. Results in this paper may be useful for the
      optical switching with the combined effects of self-phase modulation, cross-phase
      modulation, and negative coherent coupling.

PMID- 22463290
TI  - Counting solutions from finite samplings.
AB  - We formulate the solution counting problem within the framework of the inverse
      Ising problem and use fast belief propagation equations to estimate the entropy
      whose value provides an estimate of the true one. We test this idea on both
      diluted models [random 2-SAT (2-satisfiability) and 3-SAT problems] and a fully
      connected model (binary perceptron), and show that when the constraint density is
      small, this estimate can be very close to the true value. The information stored
      by the salamander retina under the natural movie stimuli can also be estimated,
      and our result is consistent with that obtained by the Monte Carlo method. Of
      particular significance is that the sizes of other metastable states for this
      real neuronal network are predicted.

PMID- 22463291
TI  - Multiscale ensemble clustering for finding modules in complex networks.
AB  - The identification of modules in complex networks is important for the
      understanding of systems. Here, we propose an ensemble clustering method
      incorporating node groupings in various sizes and the sequential removal of weak
      ties between nodes which are rarely grouped together. This method successfully
      detects modules in various networks, such as hierarchical random networks and the
      American college football network, with known modular structures. Some of the
      results are compared with those obtained by modularity optimization and K-means
      clustering.

PMID- 22463292
TI  - Reciprocal relationships in collective flights of homing pigeons.
AB  - Collective motion of bird flocks can be explained via the hypothesis of many
      wrongs and/or a structured leadership mechanism. In pigeons, previous studies
      have shown that there is a well-defined hierarchical structure and certain
      specific individuals occupy more dominant positions, suggesting that leadership
      by the few individuals drives the behavior of the collective. Conversely, by
      analyzing the same datasets, we uncover a more egalitarian mechanism. We show
      that both reciprocal relationships and a stratified hierarchical leadership are
      important and necessary in the collective movements of pigeon flocks. Rather than
      birds adopting either exclusive averaging or leadership strategies, our
      experimental results show that it is an integrated combination of both compromise
      and leadership which drives the group's movement decisions.

PMID- 22463293
TI  - Collective dynamics of self-propelled sphere-dimer motors.
AB  - The collective dynamics of ensembles of chemically powered sphere dimer motors is
      investigated. Sphere dimers are self-propelled nanomotors built from linked
      catalytic and noncatalytic spheres. They consume fuel in the environment and
      utilize the resulting self-generated concentration gradients to produce directed
      motion along their internuclear axes. In collections of such motors, the
      individual motors interact through forces that arise from concentration
      gradients, hydrodynamic coupling, and direct intermolecular forces. Under
      nonequilibrium conditions it is found that the sphere dimer motors self-assemble
      into transient aggregates with distinctive structural correlations and exhibit
      swarming where the aggregates propagate through the system. The mean square
      displacement of a dimer motor in the ensemble displays short-time ballistic and
      long-time diffusive regimes and, for ensembles containing many motors, an
      increasingly prominent intermediate regime. The self-diffusion coefficient of a
      motor in a many-motor system behaves differently from that of an isolated motor,
      and the decay of orientational correlations is a nonmonotonic function of the
      number of motors. The results presented here illustrate the phenomena to be
      expected in applications, such as cargo transport, where many motors may act in
      consort.

PMID- 22463294
TI  - Empirical correction of a toy climate model.
AB  - Improving the accuracy of forecast models for physical systems such as the
      atmosphere is a crucial ongoing effort. The primary focus of recent research on
      these highly nonlinear systems has been errors in state estimation, but as that
      error has been successfully diminished, the role of model error in forecast
      uncertainty has duly increased. The present study is an investigation of an
      empirical model correction procedure involving the comparison of short forecasts
      with a reference "truth" system during a training period, in order to calculate
      systematic (1) state-independent model bias and (2) state-dependent error
      patterns. An estimate of the likelihood of the latter error component is computed
      from the current state at every time step of model integration. The effectiveness
      of this technique is explored in a realistic scenario, in which the model is
      structurally different (in dynamics, dimension, and parametrization) from the
      target system. Results suggest that the correction procedure is more effective
      for reducing error and prolonging forecast usefulness than parameter tuning.
      However, the cost of this increase in average forecast accuracy is the creation
      of substantial qualitative differences between the dynamics of the corrected
      model and the true system. A method to mitigate dynamical ramifications and
      further increase forecast accuracy is presented.

PMID- 22463295
TI  - Level statistics and eigenfunctions of square torus billiards: manifesting the
      transition from regular to chaotic behaviors.
AB  - We thoroughly analyze the level statistics and eigenfunctions in concentric as
      well as nonconcentric square torus billiards. We confirm the characteristics of
      quantum and classical correspondence and the existence of scarred and
      superscarred modes in concentric square torus billiards. Furthermore, we not only
      verify that the transition from regular to chaotic behaviors can be manifested in
      nonconcentric square torus billiards, but also develop an analytical distribution
      to excellently fit the numerical level statistics. Finally, we intriguingly
      observe that numerous eigenstates commonly exhibit the wave patterns to be an
      ensemble of classical diamond trajectories, as the effective wavelengths are
      considerably shorter than the size of internal hole.

PMID- 22463296
TI  - Application of a trace formula to the spectra of flat three-dimensional
      dielectric resonators.
AB  - The length spectra of flat three-dimensional dielectric resonators of circular
      shape were determined from a microwave experiment. They were compared to a
      semiclassical trace formula obtained within a two-dimensional model based on the
      effective index of refraction approximation and a good agreement was found. It
      was necessary to take into account the dispersion of the effective index of
      refraction for the two-dimensional approximation. Furthermore, small deviations
      between the experimental length spectrum and the trace formula prediction were
      attributed to the systematic error of the effective index of refraction
      approximation. In summary, the methods developed in this article enable the
      application of the trace formula for two-dimensional dielectric resonators also
      to realistic, flat three-dimensional dielectric microcavities and -lasers,
      allowing for the interpretation of their spectra in terms of classical periodic
      orbits.

PMID- 22463297
TI  - Plastic bottle oscillator as an on-off-type oscillator: experiments, modeling,
      and stability analyses of single and coupled systems.
AB  - An oscillatory system called a plastic bottle oscillator is studied, in which the
      downflow of water and upflow of air alternate periodically in an upside-down
      plastic bottle containing water. It is demonstrated that a coupled two-bottle
      system exhibits in- and antiphase synchronization according to the nature of
      coupling. A simple ordinary differential equation is deduced to interpret the
      characteristics of a single oscillator. This model is also extended to coupled
      oscillators, and the model reproduces the essential features of the experimental
      observations.

PMID- 22463298
TI  - Transition from unidirectional to delayed bidirectional coupling in optically
      coupled semiconductor lasers.
AB  - We investigate the transition from unidirectional to delayed bidirectional
      coupling of semiconductor lasers. By tuning the coupling strength in one
      direction we show how the locking region evolves as a function of the detuning
      and coupling strength. We consider two representative values of the relaxation
      oscillation damping: one where the relaxation oscillations are very underdamped
      and one where they are very overdamped. Qualitatively different dynamical
      scenarios are shown to emerge for each case. Several features of the delayed
      bidirectional system can be seen as remaining from the unidirectional system
      while others clearly arise due to the delayed coupling and are similar to effects
      seen in delayed feedback configurations.

PMID- 22463299
TI  - Crenelated fast oscillatory outputs of a two-delay electro-optic oscillator.
AB  - An electro-optic oscillator subject to two distinct delayed feedbacks has been
      designed to develop pronounced broadband chaotic output. Its route to chaos
      starts with regular pulsating gigahertz oscillations that we investigate both
      experimentally and theoretically. Of particular physical interest are the
      transitions to various crenelated fast time-periodic oscillations, prior to the
      onset of chaotic regimes. The two-delay problem is described mathematically by
      two coupled delay-differential equations, which we analyze by using multiple-time
      scale methods. We show that the interplay of a large delay and a relatively small
      delay is responsible for the onset of fast oscillations modulated by a slowly
      varying square-wave envelope. As the bifurcation parameter progressively
      increases, this envelope undergoes a sequence of bifurcations that corresponds to
      successive fixed points of a sine map.

PMID- 22463300
TI  - Remote synchronization in star networks.
AB  - We study phase synchronization in a network motif with a starlike structure in
      which the central node's (the hub's) frequency is strongly detuned against the
      other peripheral nodes. We find numerically and experimentally a regime of remote
      synchronization (RS), where the peripheral nodes form a phase synchronized
      cluster, while the hub remains free with its own dynamics and serves just as a
      transmitter for the other nodes. We explain the mechanism for this RS by the
      existence of a free amplitude and also show that systems with a fixed or constant
      amplitude, such as the classic Kuramoto phase oscillator, are not able to
      generate this phenomenon. Further, we derive an analytic expression which
      supports our explanation of the mechanism.

PMID- 22463301
TI  - Zero-lag synchronization and bubbling in delay-coupled lasers.
AB  - We show experimentally that two semiconductor lasers mutually coupled via a
      passive relay fiber loop exhibit chaos synchronization at zero lag, and study how
      this synchronized regime is lost as the lasers' pump currents are increased. We
      characterize the synchronization properties of the system with high temporal
      resolution in two different chaotic regimes, namely, low-frequency fluctuations
      and coherence collapse, identifying significant differences between them. In
      particular, a marked decrease in synchronization quality develops as the lasers
      enter the coherence collapse regime. Our high-resolution measurements allow us to
      establish that synchronization loss is associated with bubbling events, the
      frequency of which increases with increasing pump current.

PMID- 22463302
TI  - Covariant hydrodynamic Lyapunov modes and strong stochasticity threshold in
      Hamiltonian lattices.
AB  - We scrutinize the reliability of covariant and Gram-Schmidt Lyapunov vectors for
      capturing hydrodynamic Lyapunov modes (HLMs) in one-dimensional Hamiltonian
      lattices. We show that, in contrast with previous claims, HLMs do exist for any
      energy density, so that strong chaos is not essential for the appearance of
      genuine (covariant) HLMs. In contrast, Gram-Schmidt Lyapunov vectors lead to
      misleading results concerning the existence of HLMs in the case of weak chaos.

PMID- 22463303
TI  - Weakly subcritical stationary patterns: Eckhaus instability and homoclinic
      snaking.
AB  - The transition from subcritical to supercritical stationary periodic patterns is
      described by the one-dimensional cubic-quintic Ginzburg-Landau equation A(t) =
      MUA + A(xx) + i(a(1)|A|(2)A(x) + a(2)A(2)A(x)*) + b|A|(2)|A - |A|(4)A, where
      A(x,t) represents the pattern amplitude and the coefficients MU, a(1), a(2), and
      b are real. The conditions for Eckhaus instability of periodic solutions are
      determined, and the resulting spatially modulated states are computed. Some of
      these evolve into spatially localized structures in the vicinity of a Maxwell
      point, while others resemble defect states. The results are used to shed light on
      the behavior of localized structures in systems exhibiting homoclinic snaking
      during the transition from subcriticality to supercriticality.

PMID- 22463304
TI  - Transition from spatial coherence to incoherence in coupled chaotic systems.
AB  - We investigate the spatio-temporal dynamics of coupled chaotic systems with
      nonlocal interactions, where each element is coupled to its nearest neighbors
      within a finite range. Depending upon the coupling strength and coupling radius,
      we find characteristic spatial patterns such as wavelike profiles and study the
      transition from coherence to incoherence leading to spatial chaos. We analyze the
      origin of this transition based on numerical simulations and support the results
      by theoretical derivations, identifying a critical coupling strength and a
      scaling relation of the coherent profiles. To demonstrate the universality of our
      findings, we consider time-discrete as well as time-continuous chaotic models
      realized as a logistic map and a Rossler or Lorenz system, respectively. Thereby,
      we establish the coherence-incoherence transition in networks of coupled
      identical oscillators.

PMID- 22463305
TI  - Control of turbulence in heterogeneous excitable media.
AB  - Control of turbulence in two kinds of typical heterogeneous excitable media by
      applying a combined method is investigated. It is found that local-low-amplitude
      and high-frequency pacing (LHP) is effective to suppress turbulence if the
      deviation of the heterogeneity is minor. However, LHP is invalid when the
      deviation is large. Studies show that an additional radial electric field can
      greatly increase the efficiency of LHP. The underlying mechanisms of successful
      control in the two kinds of cases are different and are discussed separately.
      Since the developed strategy of combining LHP with a radial electric field can
      terminate turbulence in excitable media with a high degree of inhomogeneity, it
      has the potential contribution to promote the practical low-amplitude
      defibrillation approach.

PMID- 22463306
TI  - Computationally efficient method to construct scar functions.
AB  - The performance of a simple method [E. L. Sibert III, E. Vergini, R. M. Benito,
      and F. Borondo, New J. Phys. 10, 053016 (2008)] to efficiently compute scar
      functions along unstable periodic orbits with complicated trajectories in
      configuration space is discussed, using a classically chaotic two-dimensional
      quartic oscillator as an illustration.

PMID- 22463307
TI  - Instabilities and patterns in coupled reaction-diffusion layers.
AB  - We study instabilities and pattern formation in reaction-diffusion layers that
      are diffusively coupled. For two-layer systems of identical two-component
      reactions, we analyze the stability of homogeneous steady states by exploiting
      the block symmetric structure of the linear problem. There are eight possible
      primary bifurcation scenarios, including a Turing-Turing bifurcation that
      involves two disparate length scales whose ratio may be tuned via the interlayer
      coupling. For systems of n-component layers and nonidentical layers, the linear
      problem's block form allows approximate decomposition into lower-dimensional
      linear problems if the coupling is sufficiently weak. As an example, we apply
      these results to a two-layer Brusselator system. The competing length scales
      engineered within the linear problem are readily apparent in numerical
      simulations of the full system. Selecting a sqrt[2]:1 length-scale ratio produces
      an unusual steady square pattern.

PMID- 22463308
TI  - Optimal phase description of chaotic oscillators.
AB  - We introduce an optimal phase description of chaotic oscillations by generalizing
      the concept of isochrones. On chaotic attractors possessing a general phase
      description, we define the optimal isophases as Poincare surfaces showing return
      times as constant as possible. The dynamics of the resultant optimal phase is
      maximally decoupled from the amplitude dynamics and provides a proper description
      of the phase response of chaotic oscillations. The method is illustrated with the
      Rossler and Lorenz systems.

PMID- 22463309
TI  - Distinguishing dynamics using recurrence-time statistics.
AB  - The probability densities of the mean recurrence time, which is the average time
      needed for a system to recur to a previously visited neighborhood, are
      investigated in various dynamical regimes and are found to be in agreement with
      those of the finite-time Lyapunov exponents. The important advantages of the
      former ones are that they are easy to estimate and that comparable short time
      series are sufficient. Asymmetric distributions with exponential tails are
      observed for intermittency and crisis-induced intermittency, while for typical
      chaos, the distribution has a Gaussian shape. Further, the shape of the
      distribution distinguishes intermittent strange nonchaotic attractors from those
      appearing through fractalization and tori collision mechanisms. Furthermore,
      statistics performed on the peaks in the frequency distribution of recurrence
      times unveil scaling behavior in agreement with that obtained from the spectral
      distribution function defined as the number of peaks in the Fourier spectrum
      greater than a predefined value. The results of the present recurrence statistics
      are of relevance in classifying different dynamics and providing important
      insights into the dynamics of a system when only one realization of this system
      is available. The practical use of this approach for experimental data is shown
      on experimental electrochemical time series.

PMID- 22463310
TI  - Noise-enhanced phase synchronization in time-delayed systems.
AB  - We investigate the phenomenon of noise-enhanced phase synchronization (PS) in
      coupled time-delay systems, which usually exhibit non-phase-coherent attractors
      with complex topological properties. As a delay system is essentially an infinite
      dimensional in nature with multiple characteristic time scales, it is interesting
      and crucial to understand the interplay of noise and the time scales in achieving
      PS. In unidirectionally coupled systems, the response system adjust all its time
      scales to that of the drive, whereas both subsystems adjust their rhythms to a
      single (main time scale of the uncoupled system) time scale in bidirectionally
      coupled systems. We find similar effects for both a common and an independent
      additive Gaussian noise.

PMID- 22463311
TI  - Magnetized stratified rotating shear waves.
AB  - We present a spectral linear analysis in terms of advected Fourier modes to
      describe the behavior of a fluid submitted to four constraints: shear (with rate
      S), rotation (with angular velocity Omega), stratification, and magnetic field
      within the linear spectral theory or the shearing box model in astrophysics. As a
      consequence of the fact that the base flow must be a solution of the Euler
      Boussinesq equations, only radial and/or vertical density gradients can be taken
      into account. Ertel's theorem no longer is valid to show the conservation of
      potential vorticity, in the presence of the Lorentz force, but a similar theorem
      can be applied to a potential magnetic induction: The scalar product of the
      density gradient by the magnetic field is a Lagrangian invariant for an inviscid
      and nondiffusive fluid. The linear system with a minimal number of solenoidal
      components, two for both velocity and magnetic disturbance fields, is eventually
      expressed as a four-component inhomogeneous linear differential system in which
      the buoyancy scalar is a combination of solenoidal components (variables) and the
      (constant) potential magnetic induction. We study the stability of such a system
      for both an infinite streamwise wavelength (k(1) = 0, axisymmetric disturbances)
      and a finite one (k(1) ? 0, nonaxisymmetric disturbances). In the former case
      (k(1) = 0), we recover and extend previous results characterizing the
      magnetorotational instability (MRI) for combined effects of radial and vertical
      magnetic fields and combined effects of radial and vertical density gradients. We
      derive an expression for the MRI growth rate in terms of the stratification
      strength, which indicates that purely radial stratification can inhibit the MRI
      instability, while purely vertical stratification cannot completely suppress the
      MRI instability. In the case of nonaxisymmetric disturbances (k(1) ? 0), we only
      consider the effect of vertical stratification, and we use Levinson's theorem to
      demonstrate the stability of the solution at infinite vertical wavelength (k(3) =
      0): There is an oscillatory behavior for tau > 1+|K(2)/k(1)|, where tau = St is a
      dimensionless time and K(2) is the radial component of the wave vector at tau =
      0. The model is suitable to describe instabilities leading to turbulence by the
      bypass mechanism that can be relevant for the analysis of magnetized stratified
      Keplerian disks with a purely azimuthal field. For initial isotropic conditions,
      the time evolution of the spectral density of total energy (kinetic + magnetic +
      potential) is considered. At k(3) = 0, the vertical motion is purely oscillatory,
      and the sum of the vertical (kinetic + magnetic) energy plus the potential energy
      does not evolve with time and remains equal to its initial value. The horizontal
      motion can induce a rapid transient growth provided K(2)/k(1)>>1. This rapid
      growth is due to the aperiodic velocity vortex mode that behaves like K(h)/k(h)
      where k(h)(tau)=[k(1)(2) + (K(2) - k(1)tau)(2)](1/2) and K(h) =k(h)(0). After the
      leading phase (tau > K(2)/k(1)>>1), the horizontal magnetic energy and the
      horizontal kinetic energy exhibit a similar (oscillatory) behavior yielding a
      high level of total energy. The contribution to energies coming from the modes
      k(1) = 0 and k(3) = 0 is addressed by investigating the one-dimensional spectra
      for an initial Gaussian dense spectrum. For a magnetized Keplerian disk with a
      purely vertical field, it is found that an important contribution to magnetic and
      kinetic energies comes from the region near k(1) = 0. The limit at k(1) = 0 of
      the streamwise one-dimensional spectra of energies, or equivalently, the
      streamwise two-dimensional (2D) energy, is then computed. The comparison of the
      ratios of these 2D quantities with their three-dimensional counterparts provided
      by previous direct numerical simulations shows a quantitative agreement.

PMID- 22463312
TI  - Extraction of shear viscosity in stationary states of relativistic particle
      systems.
AB  - Starting from a classical picture of shear viscosity we construct a stationary
      velocity gradient in a microscopic parton cascade. Employing the Navier-Stokes
      ansatz we extract the shear viscosity coefficient eta. For elastic isotropic
      scatterings we find an excellent agreement with the analytic values. This
      confirms the applicability of this method. Furthermore, for both elastic and
      inelastic scatterings with pQCD based cross sections we extract the shear
      viscosity coefficient eta for a pure gluonic system and find a good agreement
      with already published calculations.

PMID- 22463313
TI  - Magnetic field amplification by small-scale dynamo action: dependence on
      turbulence models and Reynolds and Prandtl numbers.
AB  - The small-scale dynamo is a process by which turbulent kinetic energy is
      converted into magnetic energy, and thus it is expected to depend crucially on
      the nature of the turbulence. In this paper, we present a model for the small
      scale dynamo that takes into account the slope of the turbulent velocity spectrum
      v(l)proportional l([symbol see text])V}, where l and v(l) are the size of a
      turbulent fluctuation and the typical velocity on that scale. The time evolution
      of the fluctuation component of the magnetic field, i.e., the small-scale field,
      is described by the Kazantsev equation. We solve this linear differential
      equation for its eigenvalues with the quantum-mechanical WKB approximation. The
      validity of this method is estimated as a function of the magnetic Prandtl number
      Pm. We calculate the minimal magnetic Reynolds number for dynamo action,
      Rm_{crit}, using our model of the turbulent velocity correlation function. For
      Kolmogorov turbulence ([symbol see text] = 1/3), we find that the critical
      magnetic Reynolds number is Rm(crit) (K) ~ 110 and for Burgers turbulence
      ([symbol see text] = 1/2) Rm(crit)(B) ~ 2700. Furthermore, we derive that the
      growth rate of the small-scale magnetic field for a general type of turbulence is
      Gamma proportional Re((1-[symbol see text])/(1+[symbol see text])) in the limit
      of infinite magnetic Prandtl number. For decreasing magnetic Prandtl number (down
      to Pm >/~ 10), the growth rate of the small-scale dynamo decreases. The details
      of this drop depend on the WKB approximation, which becomes invalid for a
      magnetic Prandtl number of about unity.

PMID- 22463314
TI  - Effect of alcohol on single-bubble sonoluminescence.
AB  - The driving parametric regions in frequency-amplitude space and the optimal
      parameters for single-bubble sonoluminescence (SBSL) in alcohol aqueous solutions
      are studied systematically by taking measurements of the spectrum and bubble
      dynamics. The experimental results show that with an increase in alcohol
      concentration, the region shrinks and shifts. The optimized parameters differ for
      alcohol solutions having different concentrations, and SBSL driven by fixed
      parameters dims quickly and is even destroyed immediately with the addition of a
      small amount of alcohol to pure water. Furthermore, it is seen that the intensity
      of optimized SBSL decreases as the alcohol concentration increases. The
      corresponding measurements of the dynamics of the optimized SBSL bubble show that
      the maximum bubble radius at an alcohol concentration of 1.04 mM is only half
      that for pure water. Meanwhile, the optimized driving amplitude acquired by
      direct measurement and that obtained by fitting the radius-time curves with the
      Rayleigh-Plesset equation both decrease by 12% in the same comparison. Therefore,
      a decrease in the driving acoustic pressure may be an important reason for the
      decrease in the optimized SBSL intensity, which should help clarify SBSL
      mechanisms in alcohol aqueous solutions.

PMID- 22463315
TI  - Extension of the momentum transfer model to time-dependent pipe turbulence.
AB  - We analyze a possible extension of Gioia and Chakraborty's momentum transfer
      model of friction in steady turbulent pipe flows [Phys. Rev. Lett. 96, 044502
      (2006)] to the case of time- and/or space-dependent turbulent flows. The end
      result is an expression for the stress at the wall as the sum of a steady and a
      dynamic component. The steady part is obtained by using the instantaneous
      velocity in the expression for the stress at the wall of a stationary flow. The
      unsteady part is a weighted average over the history of the flow acceleration,
      with a weighting function similar to that proposed by Vardy and Brown [J. Sound
      Vibr. 259, 1011 (2003); J. Sound Vibr. 270, 233 (2004)], but naturally including
      the effect of spatial derivatives of the mean flow, as in the Brunone model
      [Brunone et al., J. Water Res. Plan. Manage. 126, 236 (2000)].

PMID- 22463316
TI  - Stability of double-diffusive double-convective miscible displacements in porous
      media.
AB  - The present study offers a paradigm on the stability of two-component miscible
      displacements in a homogeneous porous medium. The components have, in general,
      different mobility ratios, may diffuse at different rates, and are convected at
      different speeds. As a result, one of the components may lag behind the other.
      For the adopted transport models, it is found that the differences in the rates
      of diffusion and the lag between the two component fronts resulting from the
      differences in the speeds of convection can modify radically the instability
      characteristics. In particular, an unstable single-component displacement is
      always made more unstable by the presence of a second unfavorable component. The
      instability of the same flow is, on the other hand, attenuated by the presence of
      a favorable, less diffusive lagging component. However, this same flow
      instability can actually be enhanced when the favorable lagging second component
      is more diffusive. Furthermore, the larger the lag between the two components is,
      the more unstable the flow is when the lagging component is favorable to the
      displacement. An opposite trend is found when the the lagging component is
      unfavorable to the displacement. Finally, changes due to the lag between the two
      components fronts are stronger for a less diffusive lagging component and weaker
      for a more diffusive one. For illustration, these results are discussed in the
      special context of a thermal displacement where mass and heat are transported in
      the porous media.

PMID- 22463317
TI  - Pseudocompressible approximation and statistical turbulence modeling: application
      to shock tube flows.
AB  - In this work, a pseudocompressible approximation relevant for turbulent mixing
      flows encountered in shock tubes is derived. The asymptotic analysis used for
      this purpose puts forward the role played by four dimensionless numbers on the
      flow compressibility, namely, the turbulent, deformation, stratification, and
      buoyancy force Mach numbers. The existence of rapid distortion and diffusion
      dissipation regimes is also accounted for in the analysis. Some consequences of
      the derived pseudocompressible approximation on statistical turbulence models are
      discussed. In particular, the evolutions of the density variance and flux are
      examined, as well as the turbulent transport of energy. The different aspects of
      this study are assessed by performing a direct numerical simulation of a shock
      tube flow configuration.

PMID- 22463318
TI  - Direct numerical simulation of two-dimensional wall-bounded turbulent flows from
      receptivity stage.
AB  - Deterministic route to turbulence creation in 2D wall boundary layer is shown
      here by solving full Navier-Stokes equation by dispersion relation preserving
      (DRP) numerical methods for flow over a flat plate excited by wall and free
      stream excitations. Present results show the transition caused by wall excitation
      is predominantly due to nonlinear growth of the spatiotemporal wave front, even
      in the presence of Tollmien-Schlichting (TS) waves. The existence and linear
      mechanism of creating the spatiotemporal wave front was established in Sengupta,
      Rao and Venkatasubbaiah [Phys. Rev. Lett. 96, 224504 (2006)] via the solution of
      Orr-Sommerfeld equation. Effects of spatiotemporal front(s) in the nonlinear
      phase of disturbance evolution have been documented by Sengupta and Bhaumik
      [Phys. Rev. Lett. 107, 154501 (2011)], where a flow is taken from the receptivity
      stage to the fully developed 2D turbulent state exhibiting a k(-3) energy
      spectrum by solving the Navier-Stokes equation without any artifice. The details
      of this mechanism are presented here for the first time, along with another
      problem of forced excitation of the boundary layer by convecting free stream
      vortices. Thus, the excitations considered here are for a zero pressure gradient
      (ZPG) boundary layer by (i) monochromatic time-harmonic wall excitation and (ii)
      free stream excitation by convecting train of vortices at a constant height. The
      latter case demonstrates neither monochromatic TS wave, nor the spatiotemporal
      wave front, yet both the cases eventually show the presence of k(-3) energy
      spectrum, which has been shown experimentally for atmospheric dynamics in
      Nastrom, Gage and Jasperson [Nature 310, 36 (1984)]. Transition by a nonlinear
      mechanism of the Navier-Stokes equation leading to k(-3) energy spectrum in the
      inertial subrange is the typical characteristic feature of all 2D turbulent
      flows. Reproduction of the spectrum noted in atmospheric data (showing dominance
      of the k(-3) spectrum over the k(-5/3) spectrum in Nastrom et al.) in laboratory
      scale indicates universality of this spectrum for all 2D turbulent flows.
      Creation of universal features of 2D turbulence by a deterministic route has been
      established here for the first time by solving the Navier-Stokes equation without
      any modeling, as has been reported earlier in the literature by other
      researchers.

PMID- 22463319
TI  - Immiscible displacement of oil by water in a microchannel: asymmetric flow
      behavior and nonlinear stability analysis of core-annular flow.
AB  - The immiscible displacement of oil by water in a circular microchannel was
      investigated. A fused silica microchannel with an inner diameter of 250 MUm and a
      length of 7 cm was initially filled with a viscous silicone oil. Only water then
      was injected into the channel. We describe our flow observations based on the two
      dimensional images captured in the middle of the channel. The water finger
      displaced the oil and left an oil film on the channel wall. While the oil was
      being displaced at the core, the flow resistance decreased, which resulted in
      increases in water flow rate and inertia. Eventually, the water finger reached
      the channel exit and formed a core-annular flow pattern. The wavelength of the
      waves formed at the oil-water interface also increased with the increase in
      inertia. The initially symmetric interfacial waves became asymmetric with time.
      Also, the water core shifted from the center of the channel and left a thinner
      oil film on one side of the microchannel. Under all flow rates tested in this
      study, as long as the water was continuously injected, the water core was stable
      and no breakup into droplets was observed. We also discuss the flow stability
      based on nonlinear and linear stability analyses performed on the core-annular
      flow. Compared to the linear analysis, which ignores the inertia effects, the
      nonlinear analysis, which includes the inertia effects, predicts longer
      interfacial wavelengths by a factor of 1/sqrt[1-a(o)/2(We(w) + We(o)a(o)(2)/1
      a(o)(2))] where We(w) and We(o) are the Weber numbers of the water and the oil
      phases, respectively, and a(o) is the unperturbed water core radius made
      dimensionless by the channel radius.

PMID- 22463320
TI  - Thermocapillary migration in small-scale temperature gradients: application to
      optofluidic drop dispensing.
AB  - We experimentally investigate the thermocapillary migration induced by local
      laser heating of the advancing front of a growing droplet confined in a
      microfluidic channel. When heating implies an effective increase in interfacial
      tension, the laser behaves as a "soft door" whose stiffness can be tuned via the
      optical parameters (beam power and waist). The light-driven thermocapillary
      velocity of a growing droplet, which opposes the basic flow, is characterized for
      different types of fluid injection, either pressure or flow rate driven, and
      various channel aspect ratios. Measurements are interpreted using a simplified
      model for the temperature gradient at the interface, based on a purely diffusive,
      three-layer system. Considering the mean temperature gradient, we demonstrate
      that the classical large-scale temperature gradient behavior is retrieved in the
      opposite case when the thermal gradient length scale is smaller than the droplet
      size. We also demonstrate that the thermocapillary velocity is proportional to
      the smallest droplet curvature imposed by the channel confinement. This suggests
      that the thermocapillary velocity is in fact proportional to the mean temperature
      gradient and to the largest interface curvature radius, which both coincide with
      the imposed one and the spherical droplet radius in large-scale and unconfined
      situations. Furthermore, as used surfactant concentrations are largely above the
      critical micelle concentration, we propose a possible explanation, relying on
      state-of-the-art considerations on high-concentration surfactant-covered
      interfaces for the observed effective increase in interfacial tension with
      temperature. We also propose a mechanism for explaining the blocking effect at
      the scaling-law level. This mechanism involves the temporal evolution of
      hydrodynamic and thermocapillary forces, based on experimental observations. We
      finally show that this optocapillary interaction with a microfluidic droplet
      generator allows for controlling either the flow rate (valve) or the droplet size
      (sampler), depending on the imposed fluid injection conditions.

PMID- 22463321
TI  - Fluctuating hydrodynamics and turbulence in a rotating fluid: universal
      properties.
AB  - We analyze the statistical properties of three-dimensional (3D) turbulence in a
      rotating fluid. To this end we introduce a generating functional to study the
      statistical properties of the velocity field v. We obtain the master equation
      from the Navier-Stokes equation in a rotating frame and thence a set of exact
      hierarchical equations for the velocity structure functions for arbitrary angular
      velocity Omega. In particular we obtain the differential forms for the analogs of
      the well-known von Karman-Howarth relation for 3D fluid turbulence. We examine
      their behavior in the limit of large rotation. Our results clearly suggest
      dissimilar statistical behavior and scaling along directions parallel and
      perpendicular to Omega. The hierarchical relations yield strong evidence that the
      nature of the flows for large rotation is not identical to pure two-dimensional
      flows. To complement these results, by using an effective model in the small
      Omega limit, within a one-loop approximation, we show that the equal-time
      correlation of the velocity components parallel to Omega displays Kolmogorov
      scaling q(-5/3) wherein as for all other components, the equal-time correlators
      scale as q(-3) in the inertial range where q is a wave vector in 3D. Our results
      are generally testable in experiments and/or direct numerical simulations of the
      Navier-Stokes equation in a rotating frame.

PMID- 22463322
TI  - Analytical linear theory for the interaction of a planar shock wave with a two-
      or three-dimensional random isotropic acoustic wave field.
AB  - We present an analytical model that describes the linear interaction of a planar
      shock wave with an isotropic random sonic field. First, we study the interaction
      with a single-mode acoustic field. We present the exact evolution for the
      pressure, velocity, vorticity, and density field generated behind the shock wave,
      and we also calculate exact and closed analytical expressions for the asymptotic
      behavior of these modes. Applying superposition, we use the results obtained from
      the single-mode analysis in order to compute the interaction with 2D/3D isotropic
      random acoustic fields. We present analytical expressions for the average
      turbulent kinetic energy generated behind the shock, as well as the averaged
      vorticity and the density perturbations as a function of the shock strength M(1)
      and the gas compressibility gamma. We also study the acoustic energy flux emitted
      by the shock front. Exact asymptotic analytical scaling laws are given for all
      the 3D averages downstream. A detailed comparison with previous works is shown.

PMID- 22463323
TI  - Propagating solitons generated by localized perturbations on the surface of deep
      water.
AB  - We report experimental evidence of the propagating capillary solitary waves
      generated by a localized water surface perturbation. Solitons are formed at the
      air-water interface with a solid plunger and then propagate with velocities
      proportional to their amplitudes. The shape of the forward front of such solitons
      is independent of the plunger shape and is given by the hyperbolic secant
      profile. We find that the nonlinearity of capillary waves is responsible for a
      small dispersion in the capillary wave group velocity and the soliton existence.
      This dispersion can be further reduced by adding minute concentrations of
      proteins to water.

PMID- 22463324
TI  - Separation of nanoparticles by flow past a patterned substrate.
AB  - Motivated by the problem of efficiently separating nanoparticles of different
      character held in solution, we investigate trajectory deflection and particle
      trapping in flows of nanoparticle suspensions past patterned surfaces. We
      consider rigid atomistic particles suspended in a viscous liquid solvent and
      driven by a pressure gradient through a channel, one side of which has a pattern
      of alternating stripes which attract or repel the particles. We first consider
      van der Waals forces alone, where the wall interaction is obtained by summing
      over semi-infinite slabs of material having a Lennard-Jones interaction with or
      without an attractive term, yielding a force field with nontrivial three
      dimensional spatial variation. This wall interaction can either trap particles on
      the attractive stripes or deflect the trajectories of mobile particles away from
      the direction of mean flow. Using molecular dynamics simulations we determine the
      motion of particles of different sizes in this potential, and observe distinct
      but modest deflections of several degrees from the direction of the imposed fluid
      flow. The effects of electrostatic interactions are considered by decorating the
      particles and walls with opposite charges, resulting in significantly more
      trapping and larger deflection angles. We use Langevin simulations to treat the
      motion of larger particles in the van der Waals case, and again observe particle
      trapping and deflection, although the numerical details of the results differ
      from the molecular dynamics simulations. In the Langevin case we are furthermore
      able to obtain bounds on the deflection angle from an analysis of the associated
      Fokker-Planck equation. We conclude that patterned surfaces deflect particle
      trajectories to a degree depending on their size, and may be used as a vector
      chromatography separation technique.

PMID- 22463325
TI  - Direct measurements of air layer profiles under impacting droplets using high
      speed color interferometry.
AB  - A drop impacting on a solid surface deforms before the liquid makes contact with
      the surface. We directly measure the time evolution of the air layer profile
      under the droplet using high-speed color interferometry, obtaining the air layer
      thickness before and during the wetting process. Based on the time evolution of
      the extracted profiles obtained at multiple times, we measure the velocity of air
      exiting from the gap between the liquid and the solid, and account for the
      wetting mechanism and bubble entrapment. The present work offers a tool to
      accurately measure the air layer profile and quantitatively study the impact
      dynamics at a short time scale before impact.

PMID- 22463326
TI  - Effective viscosity of magnetic nanofluids through capillaries.
AB  - The simultaneous effect of magnetic field and temperature on the capillary
      viscosity of magnetic nanofluid is an important parameter for a new class of
      applications such as nanoduct flow, nanomotors, micro- and nanofluidic devices,
      for transformer cooling, magnetic targeted drug delivery, etc. The effective
      viscosity of a nanofluid is explained based on the rotation of the particles and
      the effect of torque on it due to an externally applied magnetic field. Two types
      of fluids are used here, temperature-sensitive and non-temperature-sensitive
      magnetic nanofluids. In both types of fluids, decrease in effective viscosity
      with temperature is observed, but in both cases the mechanism for the decrement
      is quite different. One is due to temperature dependence of the magnetic moment
      and the other is due to removal of the secondary surfactant. For temperature
      sensitive magnetic nanofluids, a Curie temperature of ~80  degrees C is extracted
      from this study. For non-temperature-sensitive magnetic nanofluids ~65% of the
      secondary surfactant is removed for a change in temperature, DeltaT = 40  degrees
      C. This is analogous with removal of a drug from magnetic particles for targeted
      drug delivery. Further, a linear dependence of effective viscosity with different
      capillary size and xi (angle between magnetic field and flow direction,
      xiepsilon[0,pi/2]) is also observed. This linear dependence can also be a good
      approximation for the study of magnetic drug targeting, as in the human body the
      capillaries are of different sizes, and the externally applied magnetic field is
      not always parallel or perpendicular to the drug flow direction.

PMID- 22463327
TI  - Unsteady relativistic shock-wave diffraction by cylinders and spheres.
AB  - The unsteady relativistic shock-wave diffraction patterns generated by a
      relativistic blast wave impinging on a circular cylinder and a sphere are
      numerically simulated using some high-resolution relativistic kinetic beam
      schemes in a general coordinate system for solving the relativistic Euler
      equations of gas dynamics. The diffraction patterns are followed through about 6
      radii of travel of the incident shock past the body. The complete diffraction
      patterns, including regular reflection, transition from regular to Mach
      reflection, slip lines, and the complex shock-on-shock interaction at the wake
      region resulting from the Mach shocks collision behind the body are reported in
      detail. Computational results of several incident shock Mach numbers covering the
      near ultrarelativistic limit are studied. Various contours of flow properties
      including the Lorentz factor and velocity streamline plots are also presented to
      add a better understanding of the complex diffraction phenomena. The three
      dimensional relieving effects of the sphere cases are evident and can be
      quantitatively evaluated as compared with the corresponding cylinder cases.

PMID- 22463328
TI  - Effects of microstructure on flow properties of fibrous porous media at moderate
      Reynolds number.
AB  - In this study, effects of microstructure on the viscous permeability and
      Forchheimer coefficient of monodispersed fibers are investigated. The porous
      material is represented by a unit cell which is assumed to be repeated throughout
      the medium. Based on the orientation of the fibers in the space, fibrous media
      are divided into three categories: one-, two-, and three-directional (1D, 2D, and
      3D) structures. Parallel and transverse flow through square arrangements of 1D
      fibers, simple 2D mats, and 3D simple cubic structures are solved numerically
      over a wide range of porosity (0.35 < epsilon < 0.95) and Reynolds number (0.01 <
      Re < 200). The results are used to calculate the permeability and the inertial
      coefficient of the considered geometries. An experimental study is performed; the
      flow coefficients of three different ordered tube banks in the moderate range of
      Reynolds number (0.001 < Re < 15) are determined. The numerical results are
      successfully compared with the present and the existing experimental data in the
      literature. The results suggest that the permeability and Forchheimer coefficient
      are functions of porosity and fiber orientation. A comparison of the experimental
      and numerical results with the Ergun equation reveals that this equation is not
      suitable for highly porous materials. As such, accurate correlations are proposed
      for determining the Forchheimer coefficient in fibrous porous media.

PMID- 22463329
TI  - Splash control of drop impacts with geometric targets.
AB  - Drop impacts on solid and liquid surfaces exhibit complex dynamics due to the
      competition of inertial, viscous, and capillary forces. After impact, a liquid
      lamella develops and expands radially, and under certain conditions, the outer
      rim breaks up into an irregular arrangement of filaments and secondary droplets.
      We show experimentally that the lamella expansion and subsequent breakup of the
      outer rim can be controlled by length scales that are of comparable dimension to
      the impacting drop diameter. Under identical impact parameters (i.e., fluid
      properties and impact velocity) we observe unique splashing dynamics by varying
      the target cross-sectional geometry. These behaviors include (i) geometrically
      shaped lamellae and (ii) a transition in splashing stability, from regular to
      irregular splashing. We propose that regular splashes are controlled by the
      azimuthal perturbations imposed by the target cross-sectional geometry and that
      irregular splashes are governed by the fastest-growing unstable Plateau-Rayleigh
      mode.

PMID- 22463330
TI  - Thermohydrodynamics of boiling in a van der Waals fluid.
AB  - We present a modeling approach that enables numerical simulations of a boiling
      Van der Waals fluid based on the diffuse interface description. A boundary
      condition is implemented that allows in and out flux of mass at constant external
      pressure. In addition, a boundary condition for controlled wetting properties of
      the boiling surface is also proposed. We present isothermal verification cases
      for each element of our modeling approach. By using these two boundary conditions
      we are able to numerically access a system that contains the essential physics of
      the boiling process at microscopic scales. Evolution of bubbles under film
      boiling and nucleate boiling conditions are observed by varying boiling surface
      wettability. We observe flow patters around the three-phase contact line where
      the phase change is greatest. For a hydrophilic boiling surface, a complex flow
      pattern consistent with vapor recoil theory is observed.

PMID- 22463331
TI  - Relativistic magnetohydrodynamics in one dimension.
AB  - We derive a number of solutions for one-dimensional dynamics of relativistic
      magnetized plasma that can be used as benchmark estimates in relativistic
      hydrodynamic and magnetohydrodynamic numerical codes. First, we analyze the
      properties of simple waves of fast modes propagating orthogonally to the magnetic
      field in relativistically hot plasma. The magnetic and kinetic pressures obey
      different equations of state, so that the system behaves as a mixture of gases
      with different polytropic indices. We find the self-similar solutions for the
      expansion of hot strongly magnetized plasma into vacuum. Second, we derive linear
      hodograph and Darboux equations for the relativistic Khalatnikov potential, which
      describe arbitrary one-dimensional isentropic relativistic motion of cold
      magnetized plasma and find their general and particular solutions. The obtained
      hodograph and Darboux equations are very powerful: A system of highly nonlinear,
      relativistic, time-dependent equations describing arbitrary (not necessarily self
      similar) dynamics of highly magnetized plasma reduces to a single linear
      differential equation.

PMID- 22463332
TI  - Charging of dust in thermal collisional plasmas.
AB  - Thermal strongly collisional dusty plasma is studied. The electrical neutrality
      of the plasma suggests that the gas phase has some electrostatic energy when the
      plasma contains charged dust grains. The value of this energy determines the
      interphase interaction and ionization balance in the plasma. Proceeding from
      this, a new method of calculation of the dust grains' charges in plasmas with any
      number of ions (down to zero) has been proposed. The correspondence between the
      theory and the experimental data is demonstrated.

PMID- 22463333
TI  - Fully variational average atom model with ion-ion correlations.
AB  - An average atom model for dense ionized fluids that includes ion correlations is
      presented. The model assumes spherical symmetry and is based on density
      functional theory, the integral equations for uniform fluids, and a variational
      principle applied to the grand potential. Starting from density functional theory
      for a mixture of classical ions and quantum mechanical electrons, an approximate
      grand potential is developed, with an external field being created by a central
      nucleus fixed at the origin. Minimization of this grand potential with respect to
      electron and ion densities is carried out, resulting in equations for effective
      interaction potentials. A third condition resulting from minimizing the grand
      potential with respect to the average ion charge determines the noninteracting
      electron chemical potential. This system is coupled to a system of point ions and
      electrons with an ion fixed at the origin, and a closed set of equations is
      obtained. Solution of these equations results in a self-consistent electronic and
      ionic structure for the plasma as well as the average ionization, which is
      continuous as a function of temperature and density. Other average atom models
      are recovered by application of simplifying assumptions.

PMID- 22463334
TI  - Experimental demonstration of a slippage-dominant free-electron laser amplifier.
AB  - We report the first experimental demonstration of a slippage-dominant free
      electron laser (FEL) amplifier using a 140-fs full width at half maximum
      broadband seed laser pulse. The evolution of the longitudinal phase space of a
      laser seeded FEL amplifier in the slippage-dominant regime was experimentally
      characterized. We observed, for the first time, that the pulse duration of the
      FEL is primarily determined by the slippage between the seed laser and the
      electron beam. With a +/- 1% variation in the electron-beam energy, we
      demonstrated reasonably good longitudinal coherence and a +/- 2% spectral tuning
      range. The experimentally observed temporal and spectral evolution of the
      slippage-dominant FEL was verified by the numerical simulations.

PMID- 22463335
TI  - Generating nearly single-cycle pulses with increased intensity and strongly
      asymmetric pulses of petawatt level.
AB  - Generation of petawatt-class pulses with a nearly single-cycle duration or with a
      strongly asymmetric longitudinal profile using a thin plasma layer are
      investigated via particle-in-cell simulations and the analytical flying mirror
      model. It is shown that the transmitted pulses having a duration as short as
      about 4 fs (1.2 laser cycles) or one-cycle front (tail) asymmetric pulses with
      peak intensity of about 10^{21}W/cm^{2} can be produced by optimizing system
      parameters. Here, a new effect is found for the shaping of linearly polarized
      laser pulses, owing to which the peak amplitude of the transmitted pulse becomes
      larger than that of the incoming pulse, and intense harmonics are generated.
      Characteristics of the transmitting window are then studied for different
      parameters of laser pulse and plasma layer. For a circular polarization, it is
      shown that the flying mirror model developed for shaping laser pulses with
      ultrathin foils can be successfully applied to plasma layers having a thickness
      of about the laser wavelength, which allows the shape of the transmitted pulse to
      be analytically predicted.

PMID- 22463336
TI  - Nonlinear electromagnetic perturbations in a degenerate ultrarelativistic
      electron-positron plasma.
AB  - Nonlinear propagation of fast and slow magnetosonic perturbation modes in an
      ultrarelativistic, ultracold, degenerate (extremely dense) electron positron (EP)
      plasma (containing ultrarelativistic, ultracold, degenerate electron and positron
      fluids) has been investigated by the reductive perturbation method. The Alfven
      wave velocity is modified due to the presence of the enthalpy correction in the
      fluid equations of motion. The degenerate EP plasma system (under consideration)
      supports the Korteweg-de Vries (KdV) solitons, which are associated with either
      fast or slow magnetosonic perturbation modes. It is found that the
      ultrarelativistic model leads to compressive (rarefactive) electromagnetic
      solitons corresponding to the fast (slow) wave mode. There are certain critical
      angles, theta(c), at which no soliton solution is found corresponding to the fast
      wave mode. For the slow mode, the magnetic-field intensity affects both the
      soliton amplitude and width. It is also illustrated that the basic features of
      the electromagnetic solitary structures, which are found to exist in such a
      degenerate EP plasma, are significantly modified by the effects of enthalpy
      correction, electron and positron degeneracy, magnetic-field strength, and the
      relativistic effect. The applications of the results in a pair-plasma medium,
      which occurs in many astrophysical objects (e.g., pulsars, white dwarfs, and
      neutron stars) are briefly discussed.

PMID- 22463337
TI  - Microdiffusion in (2 + 1)-dimensional chain-bundle dusty-plasma liquids.
AB  - Microdiffusion in a (2 + 1)-dimensional liquid with flexible long longitudinal
      chain bundles, formed by negatively charged dusts suspended in a low-pressure Ar
      gaseous discharge, is investigated. With increasing time scale tau, the
      transverse hopping dominated displacement induces the transition from the sub- to
      the superdiffusion of the single dust, and the growth of spatial displacement
      correlation of two dusts, which suppresses their relative diffusion. The rise
      time of displacement correlation increases with dust separation. The bond
      breaking around the hopping cluster boundary is the main source for long time
      relative diffusion and causes the presence of the multiple shoulders in the fat
      tails of the non-Gaussian relative displacement histograms. The stronger
      longitudinal coupling than the transverse coupling strongly enhances the motion
      correlation over much larger separation, and suppresses the bond-breaking rate
      and the relative diffusion of the longitudinal dust pairs.

PMID- 22463338
TI  - Spectra of ion density and potential fluctuations in weakly ionized plasmas in
      the presence of dust grains.
AB  - The spectral densities of ion density and electrostatic potential fluctuations
      are derived in the framework of a self-consistent kinetic model of partially
      ionized dusty plasmas in the low-frequency regime. Neutral gas density can be
      responsible for significant modifications of the fluctuation level, hence the
      inclusion of the effect of neutrals is essential for a more realistic comparison
      with experiments, especially if spectral measurements are intended for dust
      diagnostic purposes. Comparison with the multicomponent model, attractive due to
      its simplicity as compared to the self-consistent one, is carried out to
      establish its limits of validity. Numerical calculations are performed for
      parameters typical of low-temperature plasma discharges. A criterion is derived
      for the omission of plasma discreteness in the low-frequency regime.

PMID- 22463339
TI  - Stability and evolution of wave packets in strongly coupled degenerate plasmas.
AB  - We study the nonlinear propagation of electrostatic wave packets in a collisional
      plasma composed of strongly coupled ions and relativistically degenerate
      electrons. The equilibrium of ions is maintained by an effective temperature
      associated with their strong coupling, whereas that of electrons is provided by
      the relativistic degeneracy pressure. Using a multiple-scale technique, a (3 + 1)
      dimensional coupled set of nonlinear Schrodinger-like equations with nonlocal
      nonlinearity is derived from a generalized viscoelastic hydrodynamic model. These
      coupled equations, which govern the dynamics of wave packets, are used to study
      the oblique modulational instability of a Stoke's wave train to a small plane
      wave perturbation. We show that the wave packets, though stable to the parallel
      modulation, become unstable against oblique modulations. In contrast to the long
      wavelength carrier modes, the wave packets with short wavelengths are shown to be
      stable in the weakly relativistic case, whereas they can be stable or unstable in
      the ultrarelativistic limit. Numerical simulation of the coupled equations
      reveals that a steady-state solution of the wave amplitude exists together with
      the formation of a localized structure in (2 + 1) dimensions. However, in the (3
      + 1)-dimensional evolution, a Gaussian wave beam self-focuses after interaction
      and blows up in a finite time. The latter is, however, arrested when the
      dispersion predominates over the nonlinearities. This occurs when the Coulomb
      coupling strength is higher or a choice of obliqueness of modulation, or a
      wavelength of excitation is different. Possible application of our results to the
      interior as well as in an outer mantle of white dwarfs are discussed.

PMID- 22463340
TI  - Coulomb-influenced collisions in aerosols and dusty plasmas.
AB  - In aerosol and dusty plasma systems, the behavior of suspended particles (grains)
      is often strongly influenced by collisions occurring between ions and particles,
      as well as between particles themselves. In determining the collision kernel or
      collision rate coefficient for such charged entities, complications arise in that
      the collision process can be completely described neither by continuum transport
      mechanics nor by free molecular (ballistic) mechanics; that is, collisions are
      transition regime processes. Further, both the thermal energy and the potential
      energy between colliding entities can strongly influence the collision rate and
      must be considered. Flux-matching theory, originally developed by Fuchs, is
      frequently applied for calculation of collision rate coefficients under these
      circumstances. However, recent work suggests that crucial assumptions in flux
      matching theory are not appropriate to describe transition regime collisions in
      the presence of potential interactions. Here, we combine dimensional analysis and
      mean first passage time calculations to infer the collision kernel between dilute
      charged entities suspended in a light background gas at thermal equilibrium. The
      motion of colliding entities is described by a Langevin equation, and Coulombic
      interactions are considered. It is found that the dimensionless collision kernel
      for these conditions, H, is a function of the diffusive Knudsen number, Kn(D) (in
      contrast to the traditional Knudsen number), and the potential energy to thermal
      energy ratio, Psi(E). For small and large Kn(D), it is found that the
      dimensionless collision kernels inferred from mean first passage time
      calculations collapse to the appropriate continuum and free molecular limiting
      forms, respectively. Further, for repulsive collisions (Psi(E) negative) or
      attractive collisions with Psi(E)<0.5, calculated results are in excellent
      agreement with flux-matching theory predictions, and the dimensionless collision
      kernel can be determined conveniently via use of the H(Kn(D)) relationship found
      for hard-sphere collisions with modified definitions of H and Kn(D) to account
      for potential energy. However, for Psi(E)>0.5, it is found that flux-matching
      theory predictions substantially underestimate the collision kernel. We find that
      the collision process in this regime is governed by the minimum of Kn(D) and
      Kn(Psi) (Kn(Psi) = 3Kn(D)/2Psi(E)), and based on calculations, propose a function
      H(Kn(D), Kn(Psi)) for collision kernel evaluation. The situations for which
      Psi(E)>0.5 apply to singly charged nanoparticles and multiply charged
      submicrometer and supermicrometer particles, and are thus prevalent in both
      aerosol and dusty plasma environments.

PMID- 22463341
TI  - Magnetic-field-line random walk in turbulence: a two-point correlation function
      description.
AB  - The standard theory of field-line random walk is based on the description of
      turbulence in the wave number space. The latter description takes into account
      the details of turbulence at small scales. Such details, however, are not
      important in the theory of random walking magnetic field lines. In the present
      paper we therefore use simple decorrelation models to estimate the field-line
      diffusion coefficient. Previous results are recovered as special limits. It is
      shown that a full analytical description is possible and that the only parameter
      controlling the field-line diffusion coefficient is the Kubo number.

PMID- 22463342
TI  - Instability of ion kinetic waves in a weakly ionized plasma.
AB  - The fundamental higher-order Landau plasma modes are known to be generally
      heavily damped. We show that these modes for the ion component in a weakly
      ionized plasma can be substantially modified by ion-neutral collisions and a dc
      electric field driving ion flow so that some of them can become unstable. This
      instability is expected to naturally occur in presheaths of gas discharges at
      sufficiently small pressures and thus affect sheaths and discharge structures.

PMID- 22463343
TI  - Multisolitons, breathers, and rogue waves for the Hirota equation generated by
      the Darboux transformation.
AB  - The determinant representation of the n-fold Darboux transformation of the Hirota
      equation is given. Based on our analysis, the 1-soliton, 2-soliton, and breathers
      solutions are given explicitly. Further, the first order rogue wave solutions are
      given by a Taylor expansion of the breather solutions. In particular, the
      explicit formula of the rogue wave has several parameters, which is more general
      than earlier reported results and thus provides a systematic way to tune
      experimentally the rogue waves by choosing different values for them.

PMID- 22463344
TI  - Axial acoustic radiation torque of a Bessel vortex beam on spherical shells.
AB  - The present paper investigates the interaction of an acoustic Bessel vortex beam
      centered on a viscoelastic polyethylene sphere and spherical shells filled with
      air or water immersed in nonviscous water and mercury, and the induced axial
      acoustic radiation torque (ART) resulting from the transfer of angular momentum.
      Closed-form series expansions for the axial ART are derived for the case of
      progressive, standing, and quasistanding waves. The ART is shown to be the result
      of acoustic absorption inside the particle's material. Numerical predictions
      shown in the form of two-dimensional (2D) plots illustrate the theory, and reveal
      new properties related to the ART of Bessel vortex beams. Potential applications
      are in particle rotation and manipulation. Other applications, such as the
      characterization of fluids from induced angular accelerations (produced by the
      ART) and containerless processing, may benefit from the analysis developed here.

PMID- 22463345
TI  - Confinement of semiflexible polymers.
AB  - A variational framework is developed to examine the equilibrium states of a
      semiflexible polymer that is constrained to lie on a fixed surface. As an
      application the confinement of a closed polymer loop of fixed length 2pi R within
      a spherical cavity of smaller radius, R(0), is considered. It is shown that an
      infinite number of distinct periodic completely attached equilibrium states
      exist, labeled by two integers: n = 2,3,4,... and p = 1,2,3,..., the number of
      periods of the polar and azimuthal angles, respectively. Small loops oscillate
      about a geodesic circle: n = 2, p = 1 is the stable ground state; states with
      higher n exhibit instabilities. If R >= 2R(0) new states appear as oscillations
      about a doubly covered geodesic circle; the state n = 3,p = 2 replaces the
      twofold as the ground state in a finite band of values of R. With increasing R,
      loop states make a transition from oscillatory and orbital behavior on crossing
      the poles, returning to oscillation upon collapse to a multiple cover of a
      geodesic circle (signaled, respectively, by an increase in p and an increase in
      n). The force transmitted to the surface does not increase monotonically with
      loop size, but does asymptotically. It behaves discontinuously where n changes.
      The contribution to energy from geodesic curvature is bounded. In large loops,
      the energy becomes dominated by a state independent contribution proportional to
      the loop size; the energy gap between the ground state and excited states
      disappears.

PMID- 22463346
TI  - Unstaggered-staggered solitons in two-component discrete nonlinear Schrodinger
      lattices.
AB  - We present stable bright solitons built of coupled unstaggered and staggered
      components in a symmetric system of two discrete nonlinear Schrodinger equations
      with the attractive self-phase-modulation nonlinearity, coupled by the repulsive
      cross-phase-modulation interaction. These mixed modes are of a "symbiotic" type,
      as each component in isolation may only carry ordinary unstaggered solitons. The
      results are obtained in an analytical form, using the variational and Thomas
      Fermi approximations (VA and TFA), and the generalized Vakhitov-Kolokolov (VK)
      criterion for the evaluation of the stability. The analytical predictions are
      verified against numerical results. Almost all the symbiotic solitons are
      predicted by the VA quite accurately and are stable. Close to a boundary of the
      existence region of the solitons (which may feature several connected branches),
      there are broad solitons which are not well approximated by the VA and are
      unstable.

PMID- 22463347
TI  - Vortex families near a spectral edge in the Gross-Pitaevskii equation with a two
      dimensional periodic potential.
AB  - We examine numerically vortex families near band edges of the Bloch wave spectrum
      for the Gross-Pitaevskii equation with two-dimensional periodic potentials and
      for the discrete nonlinear Schrodinger equation. We show that besides vortex
      families that terminate at a small distance from the band edges via fold
      bifurcations, there exist vortex families that are continued all the way to the
      band edges.

PMID- 22463348
TI  - Spatial solitons under competing linear and nonlinear diffractions.
AB  - We introduce a general model which augments the one-dimensional nonlinear
      Schrodinger (NLS) equation by nonlinear-diffraction terms competing with the
      linear diffraction. The new terms contain two irreducible parameters and admit a
      Hamiltonian representation in a form natural for optical media. The equation
      serves as a model for spatial solitons near the supercollimation point in
      nonlinear photonic crystals. In the framework of this model, a detailed analysis
      of the fundamental solitary waves is reported, including the variational
      approximation (VA), exact analytical results, and systematic numerical
      computations. The Vakhitov-Kolokolov (VK) criterion is used to precisely predict
      the stability border for the solitons, which is found in an exact analytical
      form, along with the largest total power (norm) that the waves may possess. Past
      a critical point, collapse effects are observed, caused by suitable
      perturbations. Interactions between two identical parallel solitary beams are
      explored by dint of direct numerical simulations. It is found that in-phase
      solitons merge into robust or collapsing pulsons, depending on the strength of
      the nonlinear diffraction.

PMID- 22463349
TI  - Nonlinear Schrodinger equation: generalized Darboux transformation and rogue wave
      solutions.
AB  - In this paper, we construct a generalized Darboux transformation for the
      nonlinear Schrodinger equation. The associated N-fold Darboux transformation is
      given in terms of both a summation formula and determinants. As applications, we
      obtain compact representations for the Nth-order rogue wave solutions of the
      focusing nonlinear Schrodinger equation and Hirota equation. In particular, the
      dynamics of the general third-order rogue wave is discussed and shown to exhibit
      interesting structures.

PMID- 22463350
TI  - Dipole interaction of the Quincke rotating particles.
AB  - We study the behavior of particles having a finite electric permittivity and
      conductivity in a weakly conducting fluid under the action of the external
      electric field. We consider the case when the strength of the external electric
      field is above the threshold, and particles rotate due to the Quincke effect. We
      determine the magnitude of the dipole interaction of the Quincke rotating
      particles and the shift of frequency of the Quincke rotation caused by the dipole
      interaction between the particles. It is demonstrated that depending on the
      mutual orientation of the vectors of angular velocities of particles, vector
      directed along the straight line between the centers of the particles and the
      external electric field strength vector, particles can attract or repel each
      other. In contrast to the case of nonrotating particles when the magnitude of the
      dipole interaction increases with the increase of the strength of the external
      electric field, the magnitude of the dipole interaction of the Quincke rotating
      particles either does not change or decreases with the increase of the strength
      of the external electric field depending on the strength of the external electric
      field and electrodynamic parameters of the particles.

PMID- 22463351
TI  - Iterative solution of integral equations on a basis of positive energy Sturmian
      functions.
AB  - An improvement of Weinberg's quasiparticle method for solving general one
      dimensional integral equations is presented. The method uses simple auxiliary
      Sturmian functions for positive or negative energies, and corrects iteratively
      for the truncation errors of the Sturmian expansion of the solution. Numerical
      examples are given for the solution of the Lippmann-Schwinger integral equation
      for the scattering of a particle from a potential with a repulsive core. An
      accuracy of 1:10(6) is achieved after 14 iterations, and 1:10(10) after 20
      iterations. The calculations are carried out in configuration space with an
      accuracy of 1:10(11) by using a spectral expansion method in terms of Chebyshev
      polynomials. The method can be extended to solving a Schrodinger equation with
      Coulomb and/or nonlocal potentials.

PMID- 22463352
TI  - Reduced-order molecular-dynamics model for polystyrene by equivalent-structure
      coarse graining.
AB  - This paper develops a reduced-order equivalent-structure based model for
      polystyrene in a rigid body molecular dynamics framework. In general, a coarse
      grained model for polymers is obtained by replacing a group of chemically
      connected atoms by an effective particle and deriving a coarse-grained
      interaction potential that reproduces the structure and dynamics at the desired
      length and time scale. In the current model, a detailed (~16 atoms) polystyrene
      monomer referred to as basic structural element (BSE) is replaced by an
      equivalent model with spherical backbone particles and an ellipsoidal particle
      that represents the styrene sidegroup. The governing principals of this
      homogenization is based on the mass, centroid, angular momentum, and energy
      equivalence between the detailed and the proposed reduced-order model. The bonded
      interactions parameters are readily obtained in the optimization of the
      equivalent structure from the detailed representation. The nonbonded interactions
      are treated separately. In order to capture the stereochemistry of the
      polystyrene molecule, an anisotropic biaxial nonbonded interaction potential
      function known as RE-squared (RE2) interaction has been used between pairs of
      ellipsoidal and/or spherical particles in the system. The required calibration of
      the nonbonded parameters is carried out by matching with the experimental density
      and the local structure using radial distribution function. This homogenization
      process scales up the modeling system size significantly as the higher frequency
      motions like -C-H- vibrations and sidegroup movements are suppressed. The
      accuracy of the model is established by comparing fine-scale simulation with
      explicit representations.

PMID- 22463353
TI  - Rejection-free Monte Carlo sampling for general potentials.
AB  - A Monte Carlo method to sample the classical configurational canonical ensemble
      is introduced. In contrast to the Metropolis algorithm, where trial moves can be
      rejected, in this approach collisions take place. The implementation is event
      driven; i.e., at scheduled times the collisions occur. A unique feature of the
      new method is that smooth potentials (instead of only step-wise changing ones)
      can be used. In addition to an event-driven approach, where all particles move
      simultaneously, we introduce a straight event-chain implementation. As proof of
      principle, a system of Lennard-Jones particles is simulated.

PMID- 22463354
TI  - Additional interfacial force in lattice Boltzmann models for incompressible
      multiphase flows.
AB  - The existing lattice Boltzmann models for incompressible multiphase flows are
      mostly constructed with two distribution functions: one is the order parameter
      distribution function, which is used to track the interface between different
      phases, and the other is the pressure distribution function for solving the
      velocity field. In this paper, it is shown that in these models the recovered
      momentum equation is inconsistent with the target one: an additional force is
      included in the recovered momentum equation. The additional force has the
      following features. First, it is proportional to the macroscopic velocity.
      Second, it is zero in every single-phase region but is nonzero in the interface.
      Therefore it can be interpreted as an interfacial force. To investigate the
      effects of the additional interfacial force, numerical simulations are carried
      out for the problem of Rayleigh-Taylor instability, droplet splashing on a thin
      liquid film, and the evolution of a falling droplet under gravity. Numerical
      results demonstrate that, with the increase of the velocity or the Reynolds
      number, the additional interfacial force will gradually have an important
      influence on the interface and affect the numerical accuracy.

PMID- 22463355
TI  - Estimation of drift and diffusion functions from time series data: a maximum
      likelihood framework.
AB  - Complex systems are characterized by a huge number of degrees of freedom often
      interacting in a nonlinear manner. In many cases macroscopic states, however, can
      be characterized by a small number of order parameters that obey stochastic
      dynamics in time. Recently, techniques for the estimation of the corresponding
      stochastic differential equations from measured data have been introduced. This
      paper develops a framework for the estimation of the functions and their
      respective (Bayesian posterior) confidence regions based on likelihood
      estimators. In succession, approximations are introduced that significantly
      improve the efficiency of the estimation procedure. While being consistent with
      standard approaches to the problem, this paper solves important problems
      concerning the applicability and the accuracy of estimated parameters.

PMID- 22463356
TI  - Interpretation of atomic motion in flexible molecules: accelerating molecular
      dynamics simulations.
AB  - We propose a new approach to split up the velocities of atoms of flexible
      molecules into translational, rotational, and vibrational components. As a
      result, the kinetic energy of the system can easily be expressed in terms of only
      three parts related to the above components. This is distinct from the standard
      Eckart method, where the cumbersome Coriolis contribution to the kinetic energy
      appears additionally. The absence of such a contribution within the proposed
      approach allows us to readily extend the microcanonical multiple-time-step
      dynamics of flexible molecules to the canonical-isokinetic Nose-Hoover chain
      ensemble by explicitly integrating the translational, orientational, and
      vibrational motion. The previous extensions dealt exclusively with translational
      degrees of freedom of separate atoms, leading to a limitation on the size of the
      outer time step of 100 femtoseconds. We show on molecular dynamics simulations of
      the flexible TIP3P water model that the new canonical-isokinetic formulation
      gives a possibility to significantly overcome this limitation. In particular,
      huge outer time steps of order from a few hundred femtoseconds up to several
      picoseconds can now be employed to study conformational properties without loss
      of accuracy.

PMID- 22463357
TI  - Nonperturbative renormalization group preserving full-momentum dependence:
      implementation and quantitative evaluation.
AB  - We present the implementation of the Blaizot-Mendez-Wschebor approximation scheme
      of the nonperturbative renormalization group we present in detail, which allows
      for the computation of the full-momentum dependence of correlation functions. We
      discuss its significance and its relation with other schemes, in particular, the
      derivative expansion. Quantitative results are presented for the test ground of
      scalar O(N) theories. Besides critical exponents, which are zero-momentum
      quantities, we compute the two-point function at criticality in the whole
      momentum range in three dimensions and, in the high-temperature phase, the
      universal structure factor. In all cases, we find very good agreement with the
      best existing results.

PMID- 22463358
TI  - Stochastic tipping points in climate dynamics.
AB  - A crucial question recently raised in climate dynamics concerns abrupt climate
      transitions: Are they due to a tipping point (TP) being exceeded, or is fast
      noisy dynamics the cause of their excitation? In this respect, a case study based
      on a low-order ocean model is developed to show that in an excitable dynamical
      system perturbed by noise (a possible climate condition) the TPs may have limited
      physical meaning, with the coherence resonance mechanism being predominant. The
      analysis is based on an operational definition of stochastic TP, which accounts
      for the effect of noise and reconciles formally the TP and coherence resonance
      views.

PMID- 22463359
TI  - Surface roughness and dry friction.
AB  - Persson's multiscale contact mechanics theory combined with a multiscale
      Brillouin-Prandtl-Tomlinson model is used to show that on the basis of these
      models "dry friction" [i.e., kinetic friction that remains at exceedingly small
      velocities (but still above the creep range) close to its value at higher
      velocities] should almost always occur for self-affine surfaces when the dominant
      interaction between two surfaces in contact is due to interatomic hard core
      repulsion, except for extremely smooth surfaces (i.e., surfaces with a Hurst
      index very close to 1).

PMID- 22463360
TI  - Enhancing synchrony in chaotic oscillators by dynamic relaying.
AB  - In a chain of mutually coupled oscillators, the coupling threshold for
      synchronization between the outermost identical oscillators decreases when a type
      of impurity (in terms of parameter mismatch) is introduced in the inner
      oscillator(s). The outer oscillators interact indirectly via dynamic relaying,
      mediated by the inner oscillator(s). We confirm this enhancing of critical
      coupling in the chaotic regimes of the Lorenz system, in the Rossler system in
      the absence of coupling delay, and in the Mackey-Glass system with delay
      coupling. The enhancing effect is experimentally verified in the electronic
      circuit of Rossler oscillators.

PMID- 22463361
TI  - Phase-shift inversion in oscillator systems with periodically switching
      couplings.
AB  - A system's response to external periodic changes can provide crucial information
      about its dynamical properties. We investigate the synchronization transition, an
      archetypical example of a dynamic phase transition, in the framework of such a
      temporal response. The Kuramoto model under periodically switching interactions
      has the same type of phase transition as the original mean-field model.
      Furthermore, we see that the signature of the synchronization transition appears
      in the relative delay of the order parameter with respect to the phase of
      oscillating interactions as well. Specifically, the phase shift becomes
      significantly larger as the system gets closer to the phase transition, so that
      the order parameter at the minimum interaction density can even be larger than
      that at the maximum interaction density, counterintuitively. We argue that this
      phase-shift inversion is caused by the diverging relaxation time, in a similar
      way to the resonance near the critical point in the kinetic Ising model. Our
      result, based on exhaustive simulations on globally coupled systems as well as
      scale-free networks, shows that an oscillator system's phase transition can be
      manifested in the temporal response to the topological dynamics of the underlying
      connection structure.

PMID- 22463362
TI  - Thermal boundary layer profiles in turbulent Rayleigh-Benard convection in a
      cylindrical sample.
AB  - We numerically investigate the structures of the near-plate temperature profiles
      close to the bottom and top plates of turbulent Rayleigh-Benard flow in a
      cylindrical sample at Rayleigh numbers Ra = 10(8) to Ra = 2 * 10(12) and Prandtl
      numbers Pr = 6.4 and Pr = 0.7 with the dynamical frame method [Zhou and Xia,
      Phys. Rev. Lett. 104, 104301 (2010)], thus extending previous results for quasi
      two-dimensional systems to three-dimensional systems. The dynamical frame method
      shows that the measured temperature profiles in the spatially and temporally
      local frame are much closer to the temperature profile of a laminar, zero
      pressure gradient boundary layer (BL) according to Pohlhausen than in the fixed
      reference frame. The deviation between the measured profiles in the dynamical
      reference frame and the laminar profiles increases with decreasing Pr, where the
      thermal BL is more exposed to the bulk fluctuations due to the thinner kinetic
      BL, and increasing Ra, where more plumes are passing the measurement location.

PMID- 22463363
TI  - Interaction and coalescence of large bubbles rising in a thin gap.
AB  - We present accurate measurements of the relative motion and deformation of two
      large bubbles released consecutively in a quiescent liquid confined in a thin-gap
      cell. Although the second injected bubble was smaller, we observed that, in all
      cases, it accelerated and caught up with the leading bubble. This acceleration is
      related to the wake of the leading bubble, which also induces significant changes
      in the width and curvature of the trailing bubble. On the contrary, the velocity
      of the leading bubble is unaltered during the whole interaction and coalescence
      process. Shape adaptation of the two bubbles is observed just prior to
      coalescence. After pinch-off, the liquid film is drained at a constant velocity.

PMID- 22463365
TI  - Compensation of Coulomb blocking and energy transfer in the current voltage
      characteristic of molecular conduction junctions.
AB  - We have studied the influence of both exciton effects and Coulomb repulsion on
      current in molecular nanojunctions. We show that dipolar energy-transfer
      interactions between the sites in the wire can at high voltage compensate Coulomb
      blocking for particular relationships between their values. Tuning this
      relationship may be achieved by using the effect of plasmonic nanostructure on
      dipolar energy-transfer interactions.

PMID- 22463364
TI  - Genetic polymorphism of merozoite surface protein 2 and prevalence of K76T pfcrt
      mutation in Plasmodium falciparum field isolates from Congolese children with
      asymptomatic infections.
AB  - BACKGROUND: In order to prepare the field site for future interventions, the
      prevalence of asymptomatic Plasmodium falciparum infection was evaluated in a
      cohort of children living in Brazzaville. Plasmodium falciparum merozoite surface
      protein 2 gene (msp2) was used to characterize the genetic diversity and the
      multiplicity of infection. The prevalence of mutant P. falciparum chloroquine
      resistance transporter (pfcrt) allele in isolates was also determined. METHODS:
      Between April and June 2010, 313 children below 10 years of age enrolled in the
      cohort for malaria surveillance were screened for P. falciparum infection using
      microscopy and polymerase chain reaction (PCR). The children were selected on the
      basis of being asymptomatic. Plasmodium falciparum msp2 gene was genotyped by
      allele-specific nested PCR and the pfcrt K76T mutation was detected using nested
      PCR followed by restriction endonuclease digestion. RESULTS: The prevalence of
      asymptomatic P. falciparum infections was 8.6% and 16% by microscopy and by PCR
      respectively. Allele typing of the msp2 gene detected 55% and 45% of 3D7 and FC27
      allelic families respectively. The overall multiplicity of infections (MOI) was
      1.3. A positive correlation between parasite density and multiplicity of
      infection was found. The prevalence of the mutant pfcrt allele (T76) in the
      isolates was 92%. CONCLUSION: This is the first molecular characterization of P.
      falciparum field isolates in Congolese children, four years after changing the
      malaria treatment policy from chloroquine (CQ) to artemisinin-based combination
      therapy (ACT). The low prevalence of asymptomatic infections and MOI is discussed
      in the light of similar studies conducted in Central Africa.

PMID- 22463366
TI  - Binary silver bromide-alkali bromide melts. Calculated and measured energies of
      mixing.

PMID- 22463367
TI  - Evidence that fibrinogen gamma' directly interferes with protofibril growth:
      implications for fibrin structure and clot stiffness.
AB  - BACKGROUND: Fibrinogen contains an alternatively spliced gamma-chain (gamma'),
      which mainly exists as a heterodimer with the common gammaA-chain
      (gammaA/gamma'). Fibrinogen gamma' has been reported to inhibit thrombin and
      modulate fibrin structure, but the underlying mechanisms are unknown. OBJECTIVE:
      We aimed to investigate the molecular mechanism underpinning the influence of
      gamma' on fibrin polymerization, structure and viscoelasticity. METHODS:
      gammaA/gammaA and gammaA/gamma' fibrinogens were separated using anion exchange
      chromatography. Cross-linking was controlled with purified FXIIIa and a synthetic
      inhibitor. Fibrin polymerization was analyzed by turbidity and gel-point time was
      measured using a coagulometer. We used atomic force microscopy (AFM) to image
      protofibril formation while final clot structure was assessed by confocal and
      scanning electron microscopy. Clot viscoelasticity was measured using a magnetic
      microrheometer. RESULTS: gammaA/gamma' fibrin formed shorter oligomers by AFM
      than gammaA/gammaA, which in addition gelled earlier. gammaA/gamma' clots
      displayed a non-homogenous arrangement of thin fibers compared with the uniform
      arrangements of thick fibers for gammaA/gammaA clots. These differences in clot
      structure were not due to thrombin inhibition as demonstrated in clots made with
      reptilase. Non-cross-linked gammaA/gammaA fibrin was approximately 2.7 * stiffer
      than gammaA/gamma'. Cross-linking by FXIIIa increased the stiffness of both
      fibrin variants; however, the difference in stiffness increased to approximately
      4.6 * (gammaA/gammaA vs. gammaA/gamma'). CONCLUSIONS: Fibrinogen gamma' is
      associated with the formation of mechanically weaker, non-uniform clots composed
      of thin fibers. This is caused by direct disruption of protofibril formation by
      gamma'.

PMID- 22463368
TI  - Use of the Ligasure vessel-sealing device for thoracoscopic peripheral lung
      biopsy in healthy dogs.
AB  - OBJECTIVE: To evaluate the use of a bipolar vessel-sealing device for peripheral
      lung lobe biopsy in healthy dogs. STUDY DESIGN: Experimental study. ANIMALS:
      Mature female hound dogs (n = 6). METHODS: Thoracoscopic access was obtained by
      placement of a subxiphoid telescope portal with instrument portals at the right 4
      6th intercostal spaces and the left 10th intercostal space. The 10-mm Ligasure
      Atlas device was used to collect a biopsy specimen from the periphery of the left
      cranial lung lobe. Dogs were recovered from anesthesia. Histologic evaluation was
      used to characterize the effect of biopsy technique on pulmonary tissue. Thoracic
      radiography was performed at 1, 2, 4, and ~180 days to evaluate for air leakage
      or other postoperative complications. RESULTS: Lung specimens were collected
      without complications. Postoperatively, 1 dog had some residual pneumothorax
      thought to be secondary to incomplete thoracic evacuation of air postoperatively.
      No evidence of air leakage was detected at any time point. Histologically,
      specimens had 3 distinct zones: a crush zone representing the tissue within the
      jaws of the device, a transition zone of thermally damaged parenchyma, and beyond
      that a viable zone of normal parenchyma. CONCLUSION: From these limited data, it
      appears that the Ligasure Atlas vessel-sealing device can be used for peripheral
      lung biopsy in healthy dogs. Further studies are required to evaluate the
      efficacy of the device in dogs with parenchymal disease.

PMID- 22463369
TI  - Adsorption of surfactant lipids by single-walled carbon nanotubes in mouse lung
      upon pharyngeal aspiration.
AB  - The pulmonary route represents one of the most important portals of entry for
      nanoparticles into the body. However, the in vivo interactions of nanoparticles
      with biomolecules of the lung have not been sufficiently studied. Here, using an
      established mouse model of pharyngeal aspiration of single-walled carbon
      nanotubes (SWCNTs), we recovered SWCNTs from the bronchoalveolar lavage fluid
      (BALf), purified them from possible contamination with lung cells, and examined
      the composition of phospholipids adsorbed on SWCNTs by liquid chromatography mass
      spectrometry (LC-MS) analysis. We found that SWCNTs selectively adsorbed two
      types of the most abundant surfactant phospholipids: phosphatidylcholines (PC)
      and phosphatidylglycerols (PG). Molecular speciation of these phospholipids was
      also consistent with pulmonary surfactant. Quantitation of adsorbed lipids by LC
      MS along with the structural assessments of phospholipid binding by atomic force
      microscopy and molecular modeling indicated that the phospholipids (~108
      molecules per SWCNT) formed an uninterrupted "coating" whereby the hydrophobic
      alkyl chains of the phospholipids were adsorbed onto the SWCNT with the polar
      head groups pointed away from the SWCNT into the aqueous phase. In addition, the
      presence of surfactant proteins A, B, and D on SWCNTs was determined by LC-MS.
      Finally, we demonstrated that the presence of this surfactant coating markedly
      enhanced the in vitro uptake of SWCNTs by macrophages. Taken together, this is
      the first demonstration of the in vivo adsorption of the surfactant lipids and
      proteins on SWCNTs in a physiologically relevant animal model.

PMID- 22463372
TI  - Comparative effectiveness analysis of anticoagulant strategies in a large
      observational database of percutaneous coronary interventions.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is the most commonly used
      procedure for coronary revascularization. There are multiple adjuvant
      anticoagulation strategies available. In this era of cost containment, we
      performed a comparative effectiveness analysis of clinical outcomes and cost of
      the major anticoagulant strategies across all types of PCI procedures in a large
      observational database. METHODS: A retrospective, comparative effectiveness
      analysis of the Premier observational database was conducted to determine the
      impact of anticoagulant treatment on outcomes. Multiple linear regression and
      logistic regression models were used to assess the association of initial
      antithrombotic treatment with outcomes while controlling for other factors.
      RESULTS: A total of 458,448 inpatient PCI procedures with known antithrombotic
      regimen from 299 hospitals between January 1, 2004 and March 31, 2008 were
      identified. Compared to patients treated with heparin plus glycoprotein IIb/IIIa
      inhibitor (GPI), bivalirudin was associated with a 41% relative risk reduction
      (RRR) for inpatient mortality, a 44% RRR for clinically apparent bleeding, and a
      37% RRR for any transfusion. Furthermore, treatment with bivalirudin alone
      resulted in a cost savings of $976 per case. Similar results were seen between
      bivalirudin and heparin in all end-points. Combined use of both bivalirudin and
      GPI substantially attenuated the cost benefits demonstrated with bivalirudin
      alone. CONCLUSION: Bivalirudin use was associated with both improved clinical
      outcomes and decreased hospital costs in this large "real-world" database. To our
      knowledge, this study is the first to demonstrate the ideal comparative
      effectiveness end-point of both improved clinical outcomes with decreased costs
      in PCI.

PMID- 22463370
TI  - A systematic review to identify areas of enhancements of pandemic simulation
      models for operational use at provincial and local levels.
AB  - BACKGROUND: In recent years, computer simulation models have supported
      development of pandemic influenza preparedness policies. However, U.S.
      policymakers have raised several concerns about the practical use of these
      models. In this review paper, we examine the extent to which the current
      literature already addresses these concerns and identify means of enhancing the
      current models for higher operational use. METHODS: We surveyed PubMed and other
      sources for published research literature on simulation models for influenza
      pandemic preparedness. We identified 23 models published between 1990 and 2010
      that consider single-region (e.g., country, province, city) outbreaks and multi
      pronged mitigation strategies. We developed a plan for examination of the
      literature based on the concerns raised by the policymakers. RESULTS: While
      examining the concerns about the adequacy and validity of data, we found that
      though the epidemiological data supporting the models appears to be adequate, it
      should be validated through as many updates as possible during an outbreak.
      Demographical data must improve its interfaces for access, retrieval, and
      translation into model parameters. Regarding the concern about credibility and
      validity of modeling assumptions, we found that the models often simplify reality
      to reduce computational burden. Such simplifications may be permissible if they
      do not interfere with the performance assessment of the mitigation strategies. We
      also agreed with the concern that social behavior is inadequately represented in
      pandemic influenza models. Our review showed that the models consider only a few
      social-behavioral aspects including contact rates, withdrawal from work or school
      due to symptoms appearance or to care for sick relatives, and compliance to
      social distancing, vaccination, and antiviral prophylaxis. The concern about the
      degree of accessibility of the models is palpable, since we found three models
      that are currently accessible by the public while other models are seeking public
      accessibility. Policymakers would prefer models scalable to any population size
      that can be downloadable and operable in personal computers. But scaling models
      to larger populations would often require computational needs that cannot be
      handled with personal computers and laptops. As a limitation, we state that some
      existing models could not be included in our review due to their limited
      available documentation discussing the choice of relevant parameter values.
      CONCLUSIONS: To adequately address the concerns of the policymakers, we need
      continuing model enhancements in critical areas including: updating of
      epidemiological data during a pandemic, smooth handling of large demographical
      databases, incorporation of a broader spectrum of social-behavioral aspects,
      updating information for contact patterns, adaptation of recent methodologies for
      collecting human mobility data, and improvement of computational efficiency and
      accessibility.

PMID- 22463373
TI  - Hydrogen generation in microbial reverse-electrodialysis electrolysis cells using
      a heat-regenerated salt solution.
AB  - Hydrogen gas can be electrochemically produced in microbial reverse
      electrodialysis electrolysis cells (MRECs) using current derived from organic
      matter and salinity-gradient energy such as river water and seawater solutions.
      Here, it is shown that ammonium bicarbonate salts, which can be regenerated using
      low-temperature waste heat, can also produce sufficient voltage for hydrogen gas
      generation in an MREC. The maximum hydrogen production rate was 1.6 m(3)
      H(2)/m(3).d, with a hydrogen yield of 3.4 mol H(2)/mol acetate at a salinity
      ratio of infinite. Energy recovery was 10% based on total energy applied with an
      energy efficiency of 22% based on the consumed energy in the reactor. The cathode
      overpotential was dependent on the catholyte (sodium bicarbonate) concentration,
      but not the salinity ratio, indicating high catholyte conductivity was essential
      for maximizing hydrogen production rates. The direction of the HC and LC flows
      (co- or counter-current) did not affect performance in terms of hydrogen gas
      volume, production rates, or stack voltages. These results show that the MREC can
      be successfully operated using ammonium bicarbonate salts that can be regenerated
      using conventional distillation technologies and waste heat making the MREC a
      useful method for hydrogen gas production from wastes.

PMID- 22463374
TI  - Reactions between beta-lactoglobulin and genipin: kinetics and characterization
      of the products.
AB  - In this paper, we present the first detailed study of the reaction kinetics and
      the characterization of the products from the endothermic reactions between beta
      lactoglobulin and genipin. The effects of the concentration, temperature, and pH
      were investigated. In the temperature range studied, the reaction was
      approximately a pseudo-first-order with respect to genipin and 0.22-order and 
      0.24-order with respect to beta-lactoglobulin for pH 6.75 and 10.5 with
      corresponding activation energy (E(a)) estimated to be 66.2 +/- 3.8 and 9.40 +/-
      0.36 kJ/mol, respectively. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis studies, validated by matrix-assisted laser desorption ionization
      time of flight mass spectrometry, showed the presence of oligomeric, i.e., di-,
      tri-, quadri-, and pentameric, forms of cross-linked beta-lactoglobulin by
      genipin at neutral but not alkaline pH; however, an extensive cross-linked
      network was not observed, consistent with the atomic force microscopy images. It
      was demonstrated that the reaction temperature and the concentration of genipin
      but not that of beta-lactoglobulin positively affected the extent of the cross
      linking reactions.

PMID- 22463375
TI  - Preliminary methylation analysis of prothymosin alpha genomic sequences.
AB  - Prothymosin alpha is a mammalian nuclear protein involved in cell proliferation
      and differentiation. Here, we carried out the first study of the methylation
      status of ProTalpha genomic sequences in cell lines during differentiation as
      well as in tumoral tissues. We found that there is hypermethylation in all cell
      lines analyzed with a pattern that is characteristic of each cell type revealing
      specific genomic reorganizations. The decrease of ProTalpha mRNA during
      differentiation was not accompanied by changes in the methylation status.
      Remarkably, we found that there is hypomethylation in gastrointestinal tumors
      when compared with the peritumoral tissue. The biological implications of these
      findings are discussed.

PMID- 22463376
TI  - Pregnancy outcome after gestational exposure to erythromycin - a population-based
      register study from Norway.
AB  - AIMS: Erythromycin is a macrolide antibiotic indicated for respiratory tract
      infections, genital chlamydia and skin infections. It has recently been suggested
      that erythromycin use in the first trimester of pregnancy can increase the risk
      of congenital cardiovascular malformations. This study aimed to determine whether
      erythromycin exposure in the first trimester is associated with cardiovascular or
      other malformations. METHODS: We studied 180 120 women in Norway who were
      pregnant during 2004-2007. Data on all live births stillbirths and induced
      abortions after 12 gestational weeks from The Medical Birth Registry of Norway
      (MBRN) were linked to information from the Norwegian prescription database
      (NorPD). We compared the pregnancy outcomes of women who had taken erythromycin
      (n= 1786, 1.0%), penicillin V (n= 4921, 2.7%) or amoxicillin (n= 1599, 0.9%) in
      their first trimester with outcomes of women who had not taken any systemic
      antibiotics (n= 163 653, 90.9%) during this period. RESULTS: The risk of
      cardiovascular malformations was not significantly different with or without
      exposure to erythromycin in the first trimester (adjusted OR = 1.2 [95% CI 0.8,
      1.8]) or in the most vulnerable period of heart formation (adjusted OR = 1.6 [95%
      CI 0.9-3.0]). Sub-analyses showed that the risk for any specific malformations
      was not increased with erythromycin, macrolides, penicillin V or amoxicillin
      compared with no antibiotic use in first trimester. CONCLUSIONS: This large,
      population-based register study did not find that exposure to erythromycin or
      macrolides in the first trimester of pregnancy was associated with fetal
      cardiovascular or other malformations. These results suggest that the risk of
      erythromycin use during early pregnancy, if any, is low.

PMID- 22463377
TI  - Scaling and mechanics of the felid calcaneus: geometric similarity without
      differential allometric scaling.
AB  - Six mechanically significant skeletal variables were measured on the calcanei
      from 60 Felidae specimens (22 species) to determine whether these variables were
      scaled to body mass, and to assess whether differential scaling exists. The power
      equation (y = a . x(b) ) was used to analyse the scaling of the six variables to
      body mass; we compared traditional regression methods (standardised major axis)
      to phylogenetically independent contrasts. In agreement with previous studies
      that compared these methodologies, we found no significant differences between
      methods in the allometric coefficients (b) obtained. Overall, the scaling pattern
      of the felid calcaneus conformed to the predictions of the geometric similarity
      hypothesis, but not entirely to those of the elastic similarity hypothesis. We
      found that the moment arm of the ankle extensors scaled to body mass with an
      exponent not significantly different from 0.40. This indicated that the tuber
      calcanei scaled to body mass faster than calcaneus total length. This explained
      why the effective mechanical advantage of the ankle extensors increased with body
      mass, despite the fact that limb posture does not change in felid species.
      Furthermore, this finding was consistent with the hypothesis of the isometric
      scaling of ground reaction forces. No evidence for differential scaling was found
      in any of the variables studied. We propose that this reflected the similar
      locomotor pattern of all felid species. Thus, our results suggested that the
      differences in allometric coefficients for 'large' and 'small' mammals were in
      fact caused by different types of locomotion among the species included in each
      category.

PMID- 22463378
TI  - Personalized neuromusculoskeletal modeling to improve treatment of mobility
      impairments: a perspective from European research sites.
AB  - Mobility impairments due to injury or disease have a significant impact on
      quality of life. Consequently, development of effective treatments to restore or
      replace lost function is an important societal challenge. In current clinical
      practice, a treatment plan is often selected from a standard menu of options
      rather than customized to the unique characteristics of the patient. Furthermore,
      the treatment selection process is normally based on subjective clinical
      experience rather than objective prediction of post-treatment function. The net
      result is treatment methods that are less effective than desired at restoring
      lost function. This paper discusses the possible use of personalized
      neuromusculoskeletal computer models to improve customization, objectivity, and
      ultimately effectiveness of treatments for mobility impairments. The discussion
      is based on information gathered from academic and industrial research sites
      throughout Europe, and both clinical and technical aspects of personalized
      neuromusculoskeletal modeling are explored. On the clinical front, we discuss the
      purpose and process of personalized neuromusculoskeletal modeling, the
      application of personalized models to clinical problems, and gaps in clinical
      application. On the technical front, we discuss current capabilities of
      personalized neuromusculoskeletal models along with technical gaps that limit
      future clinical application. We conclude by summarizing recommendations for
      future research efforts that would allow personalized neuromusculoskeletal models
      to make the greatest impact possible on treatment design for mobility
      impairments.

PMID- 22463379
TI  - Non-suicidal self-injury, youth, and the Internet: What mental health
      professionals need to know.
AB  - Non-suicidal self-injury (NSSI) content and related e-communication have
      proliferated on the Internet in recent years. Research indicates that many youth
      who self-injure go online to connect with others who self-injure and view others'
      NSSI experiences and share their own through text and videos platforms. Although
      there are benefits to this behaviour in terms of receiving peer support, these
      activities can introduce these young people to risks, such as NSSI reinforcement
      through the sharing of stories and strategies, as well as, risks for triggering
      of NSSI urges. Due to the nature of these risks mental health professionals need
      to know about these risks and how to effectively assess adolescents' online
      activity in order to adequately monitor the effects of the purported benefits and
      risks associated with NSSI content. This article offers research informed
      clinical guidelines for the assessment, intervention, and monitoring of online
      NSSI activities. To help bridge the gap between youth culture and mental health
      culture, these essentials include descriptions of Community, Social Networking,
      and Video/Photo Sharing websites and the terms associated with these websites.
      Assessment of these behaviours can be facilitated by a basic Functional
      Assessment approach that is further informed using specific recommended online
      questions tailored to NSSI online and an assessment of the frequency, duration,
      and time of day of the online activities. Intervention in this area should
      initially assess readiness for change and use motivational interviewing to
      encourage substitution of healthier online activities for the activities that may
      currently foster harm.

PMID- 22463380
TI  - Sidestream cigarette smoke effects on cardiovascular responses in conscious rats:
      involvement of oxidative stress in the fourth cerebral ventricle.
AB  - BACKGROUND: Cigarette exposure increases brain oxidative stress. The literature
      showed that increased brain oxidative stress affects cardiovascular regulation.
      However, no previous study investigated the involvement of brain oxidative stress
      in animals exposed to cigarette and its relationship with cardiovascular
      regulation. We aimed to evaluate the effects of central catalase inhibition on
      baroreflex and cardiovascular responses in rats exposed to sidestream cigarette
      smoke (SSCS). METHODS: We evaluated males Wistar rats (320-370 g), which were
      implanted with a stainless steel guide cannula into the fourth cerebral ventricle
      (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP)
      and heart rate (HR) measurement and drug infusion, respectively. Rats were
      exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm).
      Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 MUg/kg, bolus)
      to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP,
      50 MUg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were
      evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ,
      catalase inhibitor, 0.001 g/100 MUL) injection into the 4th V. RESULTS: Central
      catalase inhibition increased basal HR in the control group during the first 5
      minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during
      the first 15 minutes. CONCLUSION: We suggest that SSCS exposure affects
      cardiovascular regulation through its influence on catalase activity.

PMID- 22463381
TI  - The utility of the 'book biopsy' in Mohs micrographic surgery.

PMID- 22463382
TI  - hOGG1 Ser326Cys polymorphism is associated with risk of bladder cancer in a
      Chinese population: a case-control study.
AB  - Human oxoguanine glycosylase 1 (hOGG1) is a DNA repair enzyme, which plays
      important roles in the base excision repair (BER) pathway. Several studies
      reported a common polymorphism Ser326Cys (rs1052133) in hOGG1, which conferred
      the susceptibility of bladder cancer. We hypothesized that the polymorphism is
      associated with risk of bladder cancer in a Chinese population. In a case-control
      study of 1050 histologically confirmed bladder cancer patients and 1404 age and
      sex matched healthy controls, we genotyped the hOGG1 Ser326Cys polymorphism using
      TaqMan technology and assessed its association with bladder cancer risk. We found
      that the hOGG1 Ser/Cys + Ser/Ser genotypes were associated with a significantly
      increased risk of bladder cancer (adjusted odds ratio [OR] = 1.19, 95% confidence
      interval [CI] = 1.01-1.41), compared with the Cys/Cys genotype. Furthermore, the
      increased risk was more pronounced among subjects over age 65 years (OR = 1.31,
      95% CI = 1.04-1.66), male subjects (OR = 1.21, 95% CI = 1.00-1.47), ever smokers
      (OR = 1.29, 95% CI = 1.00-1.68) and heavy smokers (>20 pack-years) (OR = 1.45,
      95% CI = 1.03-2.04). No significant association was observed in the
      stratification of tumor grade and tumor stage for bladder cancer. In conclusion,
      our results suggest that hOGG1 Ser326Cys polymorphism may contribute to the
      susceptibility to bladder cancer in a Chinese population.

PMID- 22463383
TI  - Enantioselective biotransformations of racemic and meso pyrrolidine-2,5
      dicarboxamides and their application in organic synthesis.
AB  - In this paper, we report the amidase-catalyzed hydrolysis of pyrrolidine-2,5
      dicarboxamides and their application in organic synthesis. Catalyzed by
      Rhodococcus erythropolis AJ270, an amidase containing microbial whole cell
      catalyst, racemic trans-pyrrolidine-2,5-carboxamide was kinetically resolved into
      (2S,5S)-pyrrolidine-2,5-dicarboxamide and (2R,5R)-5-carbamoylpyrrolidine-2
      carboxylic acid in high yields and excellent enantioselectivity. Biocatalytic
      desymmetrization of meso cis-pyrrolidinedicarboxamide afforded enantiomerically
      pure (2R,5S)-5-carbamoylpyrrolidine-2-carboxylic acid in an almost quantitative
      yield. In both kinetic resolution and desymmetrization, the amidase always
      exhibited excellent 2R-enantioselectivity, although its catalytic efficiency was
      influenced dramatically by the steric effect of the substituent on the nitrogen
      atom of pyrrolidine ring. The synthetic potential of biotransformation was
      demonstrated by the scalable preparation of (2R,5R)- and (2R,5S)-5
      carbamoylpyrrolidine-2-carboxylic acids and their conversions to aza-nucleoside
      analogues and druglike pyrroline-fused diazepin-11(5H)-one compounds.

PMID- 22463384
TI  - Proteomic characterization of histotroph during the preimplantation phase of the
      estrous cycle in cattle.
AB  - Uterine secretions, or histotroph, are a critical component for early embryo
      survival, functioning as the sole supply of vitamins, minerals, enzymes, and
      other myriad of nutrients required by the developing conceptus before
      implantation. Histotroph is therefore a promising source for biomarkers of
      uterine function and for enhancing our understanding of the environment
      supporting early embryo development and survival. Utilizing label-free liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomics, we
      characterized the uterine proteome at two key preimplantation stages of the
      estrous cycle in high fertility cattle. We identified 300 proteins on Day 7 and
      510 proteins on Day 13 including 281 proteins shared between days. Five proteins
      were more abundant (P < 0.05) on Day 7 compared with Day 13 and included novel
      histotroph proteins cytokeratin 10 and stathmin. Twenty-nine proteins were more
      abundant (P < 0.05) including 13 unique on Day 13 compared with Day 7 and
      included previously identified legumain, metalloprotease inhibitor-2, and novel
      histotroph proteins chromogranin A and pyridoxal kinase. Functional analysis of
      the 34 differentially expressed proteins (including 14 novel to histotroph)
      revealed distinct biological roles putatively involved in early pregnancy,
      including remodelling of the uterine environment in preparation for implantation;
      nutrient metabolism; embryo growth, development and protection; maintenance of
      uterine health; and maternal immune modulation. This study is the first reported
      LC-MS/MS based global proteomic characterization of the uterine environment in
      any domesticated species before implantation and provides novel information on
      the temporal alterations in histotroph composition during critical stages for
      early embryo development and uterine function during the early establishment of
      pregnancy.

PMID- 22463385
TI  - Forest fragmentation genetics in a formerly widespread island endemic tree:
      Vateriopsis seychellarum (Dipterocarpaceae).
AB  - Habitat fragmentation and changed land use have seriously reduced population size
      in many tropical forest tree species. Formerly widespread species with limited
      gene flow may be particularly vulnerable to the negative genetic effects of
      forest fragmentation and small population size. Vateriopsis seychellarum
      (Dipterocarpaceae) is a formerly widespread canopy tree of the Seychelles, but is
      now reduced to 132 adult individuals distributed in eleven sites. Using ten
      microsatellite loci, a genetic inventory of all adult trees and a sample of 317
      progeny, we demonstrate that despite its restricted range, overall genetic
      diversity was relatively high (H(E) : 0.56). The juvenile cohort, however, had
      significantly lower allelic richness (adults R(S) : 3.91; juveniles R(S) : 2.83)
      and observed heterozygosity than adult trees (adults H(O) : 0.62; juveniles H(O)
      : 0.48). Rare alleles were fewer and kinship between individuals was stronger in
      juveniles. Significant fine-scale spatial genetic structure was observed in
      remnant adults, and parentage analysis indicated that more than 90% of sampled
      progeny disperse <25 m and pollen dispersed <50 m. The molecular data confirmed
      that two populations were derived entirely from self-fertilized offspring from a
      single surviving mother tree. These populations produce viable offspring. Despite
      this extreme genetic bottleneck, self-compatibility may provide V. seychellarum
      with some resistance to the genetic consequences of habitat fragmentation, at
      least in the short term. We discuss our findings in the context of other rare and
      threatened dipterocarp species which are vulnerable to miss-management of genetic
      resources and population fragmentation.

PMID- 22463388
TI  - The effects of acute stress and perceptual load on distractor interference.
AB  - Selective attention can be improved under conditions in which a high perceptual
      load is assumed to exhaust cognitive resources, leaving scarce resources for
      distractor processing. The present study examined whether perceptual load and
      acute stress share common attentional resources by manipulating perceptual and
      stress loads. Participants identified a target within an array of nontargets that
      were flanked by compatible or incompatible distractors. Attentional selectivity
      was measured by longer reaction times in response to the incompatible than to the
      compatible distractors. Participants in the stress group participated in a speech
      test that increased anxiety and threatened self-esteem. The effect of perceptual
      load interacted with the stress manipulation in that participants in the control
      group demonstrated an interference effect under the low perceptual load
      condition, whereas such interference disappeared under the high perceptual load
      condition. Importantly, the stress group showed virtually no interference under
      the low perceptual load condition, whereas substantial interference occurred
      under the high perceptual load condition. These results suggest that perceptual
      and stress related demands consume the same attentional resources.

PMID- 22463386
TI  - Stem cell factor-displaying simian immunodeficiency viral vectors together with a
      low conditioning regimen allow for long-term engraftment of gene-marked
      autologous hematopoietic stem cells in macaques.
AB  - Although clinical benefits have been reported in several human hematopoietic gene
      therapy trials, a remaining important goal is the transition to nonmyeloablative
      pretransplantation conditioning to decrease toxicity. Previous attempts at
      reduced intensity conditioning in nonhuman primates have resulted in only
      temporary vector marking of autologous blood cells or their persistence at low
      levels, well below the thresholds for clinical efficacy. In addition, we reasoned
      that lentiviral vector particles displaying cytokines at their surface have the
      potential to preserve stem cell fitness better than current ex vivo transduction
      protocols, which involve exposure to cytokine overstimulation. Here we show that
      the classically nonmyeloablative agent fludarabine (30 mg/m(2)/day for 3 days)
      together with low-level total body irradiation (2 Gy) and the use of a stem cell
      factor-displaying simian immunodeficiency virus-based vector, resulted in
      sustained, single-copy vector marking of autologous blood cells in two macaques
      over 3 years posttransplantation at levels averaging 1% of all lineages. This
      percentage is within the range of anticipated efficacy levels for hemophilia and
      related diseases and forms a basis for further improvement.

PMID- 22463387
TI  - Assessment of the risk of malaria re-introduction in the Maremma plain (Central
      Italy) using a multi-factorial approach.

PMID- 22463389
TI  - Error reactivity in self-paced performance: Highly-accurate individuals exhibit
      largest post-error slowing.
AB  - Reaction time is typically increased following an erroneous response. This post
      error slowing is traditionally explained by a strategic adjustment of response
      threshold towards more conservative behaviour. A recently proposed orienting
      account provides an alternative explanation for post-error slowing. According to
      this account, committing an error evokes an orienting response (OR), which
      inhibits information processing in the subsequent trial, resulting in slow and
      inaccurate performance. We tested a straightforward prediction of the orienting
      account in the context of self-paced performance, adopting an individual
      differences approach: Post-error slowing should be larger the less frequent an
      error is. To this end, participants were classified into three groups differing
      in overall performance accuracy. Larger post-error slowing and stronger post
      error accuracy decrease were observed for the high-accuracy group than for the
      two other groups. Practice pronounced the post-error accuracy decline, especially
      for the high-accuracy group. The results are consistent with the orienting
      account of post-error slowing but are problematic for accounts based on strategic
      evaluation mechanisms.

PMID- 22463390
TI  - Polysialyltransferase: a new target in metastatic cancer.
AB  - Polysialic acid (polySia) is a carbohydrate polymer critical for neuronal cell
      migration and axon pathfinding in embryonic development. Besides brain regions
      requiring persistent neuronal plasticity, polySia is essentially absent from the
      adult body. However, polySia is aberrantly re-expressed on many tumours, where it
      decorates the surface of NCAM (neuronal cell adhesion molecule) and modulates
      cell adhesion, migration and invasion. PolySia-NCAM expression is strongly
      associated with poor clinical prognosis and correlates with aggressive and
      invasive disease in many cancers, including lung cancer, neuroblastoma and
      gliomas. The synthesis of polySia is mediated by two polysialyltransferases
      (polySTs), ST8SiaIV (PST) and particularly ST8SiaII (STX) in cancer cells. The
      demonstration that polyST knock-down negates events associated with tumour cell
      dissemination indicates that PST and STX are validated targets. Selective
      inhibition of polySTs therefore presents a therapeutic opportunity to inhibit
      tumour invasion and metastasis.

PMID- 22463391
TI  - Achiral counterion control of enantioselectivity in a Bronsted acid-catalyzed
      iodolactonization.
AB  - Highly enantioselective halolactonizations have been developed that employ a
      chiral proton catalyst-N-iodosuccinimide (NIS) reagent system in which the
      Bronsted acid is used at catalyst loadings as low as 1 mol %. An approach that
      modulates the achiral counterion (equimolar to the neutral chiral ligand-proton
      complex present at low catalyst loadings) to optimize the enantioselection is
      documented for the first time in this transformation. In this way, unsaturated
      carboxylic acids are converted to gamma-lactones in high yields (up to 98% ee)
      using commercially available NIS.

PMID- 22463392
TI  - Remote ischemic perconditioning in thrombolysed stroke patients: randomized study
      of activating endogenous neuroprotection - design and MRI measurements.
AB  - BACKGROUND: Intravenous administration of alteplase is the only approved
      treatment for acute ischemic stroke. Despite the effectiveness of this treatment,
      50% of patients suffer chronic neurological disability, which may in part be
      caused by ischemia-reperfusion injury. Remote ischemic perconditioning, performed
      as a transient ischemic stimulus by blood-pressure cuff inflation to an
      extremity, has proven effective in attenuating ischemia-reperfusion injury in
      animal models of stroke. Remote ischemic perconditioning increases myocardial
      salvage in patients undergoing acute revascularization for acute myocardial
      infarction. To clarify whether a similar benefit can be obtained in patients
      undergoing thrombolysis for acute stroke, we included patients from June 2009 to
      January 2011. AIM AND DESIGN: The aims of the study are: to estimate the effect
      of remote ischemic perconditioning as adjunctive therapy to intravenous alteplase
      of acute ischemic stroke within the 4-h time window and to investigate the
      feasibility of remote ischemic perconditioning performed during transport to
      hospital in patients displaying symptoms of acute stroke. Patients are randomized
      to remote ischemic perconditioning in a single-blinded fashion during
      transportation to hospital. Only patients with magnetic resonance imaging-proven
      ischemic stroke, who subsequently are treated with intravenous alteplase, and in
      selected cases additional endovascular treatment, are finally included in the
      study. STUDY OUTCOMES: Primary end-point is penumbral salvage. Penumbra is
      defined as hypoperfused yet viable tissue identified as the mismatch between
      perfusion-weighted imaging and diffusion-weighted imaging lesion on magnetic
      resonance imaging scans. Primary outcome is a mismatch volume not progressing to
      infarction on one-month follow-up T2 fluid attenuated inversion recovery.
      Secondary end-points include: infarct growth (expansion of the diffusion-weighted
      imaging lesion) from baseline to the 24-h and one-month follow-up examination.
      Infarct growth inside and outside the acute perfusion-weighted imaging-diffusion
      weighted imaging mismatch zone is quantified by use of coregistration. Clinical
      outcome after three-months. The influence of physical activity (Physical Activity
      Scale for the Elderly score) on effect of remote ischemic perconditioning.
      Feasibility of remote ischemic perconditioning in acute stroke patients. SUMMARY:
      This phase 3 trial is the first study in patients with acute ischemic stroke to
      evaluate the effect size of remote ischemic perconditioning as a pretreatment to
      intravenous alteplase, measured as penumbral salvage on multimodal magnetic
      resonance imaging and clinical outcome after three-months follow-up.

PMID- 22463393
TI  - Analysis of several biomechanical models for the simulation of lamb liver
      behaviour using similarity coefficients from medical image.
AB  - In this study, six biomechanical models for simulating lamb liver behaviour are
      presented. They are validated using similarity coefficients from Medical Image on
      reconstructed volumes from computerised tomography images. In particular, the
      Jaccard and Hausdorff coefficients are used. Loads of 20 and 40 g are applied to
      the livers and their deformation is simulated by means of the finite element
      method. The models used are a linear elastic model, a neo-Hookean model, a Mooney
      Rivlin model, an Ogden model, a linear viscoelastic model and a viscohyperelastic
      model. The model that provided a behaviour that is closest to reality was the
      viscohyperelastic model, where the hyperelastic part was modelled with an Ogden
      model. 

PMID- 22463394
TI  - Fully nonlocal, monogamous, and random genuinely multipartite quantum
      correlations.
AB  - Local measurements on bipartite maximally entangled states can yield correlations
      that are maximally nonlocal, monogamous, and with fully random outcomes. This
      makes these states ideal for bipartite cryptographic tasks. Genuine-multipartite
      nonlocality constitutes a stronger notion of nonlocality in the multipartite
      case. Maximal genuine-multipartite nonlocality, monogamy, and random outcomes are
      thus highly desired properties for genuine-multipartite cryptographic scenarios.
      We prove that local measurements on any Greenberger-Horne-Zeilinger state can
      produce correlations that are fully genuine-multipartite nonlocal, monogamous,
      and with fully random outcomes. A key ingredient in our proof is a multipartite
      chained Bell inequality detecting genuine-multipartite nonlocality, which we
      introduce. Finally, we discuss applications to device-independent secret sharing.

PMID- 22463395
TI  - Randomness versus nonlocality and entanglement.
AB  - The outcomes obtained in Bell tests involving two-outcome measurements on two
      subsystems can, in principle, generate up to 2 bits of randomness. However, the
      maximal violation of the Clauser-Horne-Shimony-Holt inequality guarantees the
      generation of only 1.23 bits of randomness. We prove here that quantum
      correlations with arbitrarily little nonlocality and states with arbitrarily
      little entanglement can be used to certify that close to the maximum of 2 bits of
      randomness are produced. Our results show that nonlocality, entanglement, and
      randomness are inequivalent quantities. They also imply that device-independent
      quantum key distribution with an optimal key generation rate is possible by using
      almost-local correlations and that device-independent randomness generation with
      an optimal rate is possible with almost-local correlations and with almost
      unentangled states.

PMID- 22463396
TI  - Long-range quantum gates using dipolar crystals.
AB  - We propose the use of dipolar spin chains to enable long-range quantum logic
      between distant qubits. In our approach, an effective interaction between remote
      qubits is achieved by adiabatically following the ground state of the dipolar
      chain across the paramagnet to crystal phase transition. We demonstrate that the
      proposed quantum gate is particularly robust against disorder and derive scaling
      relations, showing that high-fidelity qubit coupling is possible in the presence
      of realistic imperfections. Possible experimental implementations in systems
      ranging from ultracold Rydberg atoms to arrays of nitrogen vacancy defect centers
      in diamond are discussed.

PMID- 22463397
TI  - Absolute stability of axisymmetric perturbations in strongly magnetized
      collisionless axisymmetric accretion disk plasmas.
AB  - This Letter presents a kinetic description of low-frequency and long-wavelength
      axisymmetric electromagnetic perturbations in nonrelativistic, strongly
      magnetized, and gravitationally bound axisymmetric accretion-disk plasmas in the
      collisionless regime. The analysis, carried out within the framework of the
      Vlasov-Maxwell description, relies on stationary kinetic solutions which allow
      for the simultaneous treatment of nonuniform fluid fields, stationary accretion
      flows, and temperature anisotropies. It is demonstrated that these stationary
      configurations are actually stable against axisymmetric kinetic instabilities of
      this type. As a fundamental consequence, this rules out the possibility of having
      the axisymmetric magnetorotational or thermal instabilities to arise in these
      systems.

PMID- 22463400
TI  - Differentiating the Higgs boson from the dilaton and radion at Hadron colliders.
AB  - A number of candidate theories beyond the standard model (SM) predict new scalar
      bosons below the TeV region. Among these, the radion, which is predicted in the
      Randall-Sundrum model, and the dilaton, which is predicted by the walking
      technicolor theory, have very similar couplings to those of the SM Higgs boson,
      and it is very difficult to differentiate these three spin-0 particles in the
      expected signals of the Higgs boson at the LHC and Tevatron. We demonstrate that
      the observation of the ratio sigma(gammagamma)/sigma(WW) gives a simple and
      decisive way to differentiate these, independent of the values of model
      parameters, the vacuum expectation values of the radion, and dilaton fields.

PMID- 22463402
TI  - Heavy quarkonium production and polarization.
AB  - We present a perturbative QCD factorization formalism for the production of heavy
      quarkonia of large transverse momentum p(T) at collider energies, which includes
      both the leading-power (LP) and next-to-leading-power (NLP) contributions to the
      cross section in the m(Q)(2)/p(T)(2) expansion for heavy quark mass m(Q). We
      estimate fragmentation functions in the nonrelativistic QCD formalism and
      reproduce the bulk of the large enhancement found in explicit next-to-leading
      order calculations in the color-singlet model. Heavy quarkonia produced from NLP
      channels prefer longitudinal polarization.

PMID- 22463403
TI  - Prediction of the bottomonium D-wave spectrum from full lattice QCD.
AB  - We calculate the full spectrum of D-wave states in the Upsilon system in lattice
      QCD for the first time, by using an improved version of nonrelativistic QCD on
      coarse and fine "second-generation" gluon field configurations from the MILC
      Collaboration that include the effect of up, down, strange, and charm quarks in
      the sea. By taking the 2S-1S splitting to set the lattice spacing, we determine
      the (3)D2-1S splitting to 2.3% and find agreement with experiment. Our prediction
      of the fine structure relative to the (3)D2 gives the (3)D3 at 10.181(5) GeV and
      the (3)D1 at 10.147(6) GeV. We also discuss the overlap of (3)D1 operators with
      (3)S1 states.

PMID- 22463405
TI  - 3D projection sideband cooling.
AB  - We demonstrate 3D microwave projection sideband cooling of trapped, neutral
      atoms. The technique employs state-dependent potentials that enable microwave
      photons to drive vibration-number reducing transitions. The particular cooling
      sequence we employ uses minimal spontaneous emission, and works even for
      relatively weakly bound atoms. We cool 76% of atoms to their 3D vibrational
      ground states in a site-resolvable 3D optical lattice.

PMID- 22463406
TI  - Laser radiation pressure slowing of a molecular beam.
AB  - We demonstrate deceleration of a beam of neutral strontium monofluoride molecules
      using radiative forces. Under certain conditions, the deceleration results in a
      substantial flux of detected molecules with velocities ?50  m/s. Simulations and
      other data indicate that the detection of molecules below this velocity is
      greatly diminished by transverse divergence from the beam. The observed slowing,
      from ~140  m/s, corresponds to scattering ?10(4) photons. We also observe
      longitudinal velocity compression under different conditions. Combined with
      molecular laser cooling techniques, this lays the groundwork to create slow and
      cold molecular beams suitable for trap loading.

PMID- 22463404
TI  - First observation of ground state dineutron decay: 16Be.
AB  - We report on the first observation of dineutron emission in the decay of 16Be. A
      single-proton knockout reaction from a 53  MeV/u 17B beam was used to populate
      the ground state of 16Be. 16Be is bound with respect to the emission of one
      neutron and unbound to two-neutron emission. The dineutron character of the decay
      is evidenced by a small emission angle between the two neutrons. The two-neutron
      separation energy of 16Be was measured to be 1.35(10) MeV, in good agreement with
      shell model calculations, using standard interactions for this mass region.

PMID- 22463407
TI  - Recollision dynamics and phase diagram for nonsequential double ionization with
      circularly polarized laser fields.
AB  - A semiclassical quasistatic model is used to investigate the recollision dynamics
      in circularly polarized laser fields. A velocity window for recollision to occur
      is found. Only when the return electron's orbits are irregular does significant
      double ionization take place. The model reproduces the experimental results for
      magnesium and explains the apparently conflicting experimental results in terms
      of an analytical formula that demarcates the phase diagram for the nonsequential
      double ionization in circularly polarized laser fields.

PMID- 22463399
TI  - Measurement of ZZ production in leptonic final states at sqrt[s] of 1.96 TeV at
      CDF.
AB  - In this Letter, we present a precise measurement of the total ZZ production cross
      section in pp collisions at sqrt[s]=1.96  TeV, using data collected with the CDF
      II detector corresponding to an integrated luminosity of approximately 6  fb(-1).
      The result is obtained by combining separate measurements in the four-charged
      (lll' l') and two-charged-lepton and two-neutral-lepton (llnunu) decay modes of
      the Z boson pair. The combined measured cross section for pp -> ZZ is 1.64(
      0.38)(+0.44)  pb. This is the most precise measurement of the ZZ production cross
      section in 1.96 TeV pp collisions to date.

PMID- 22463408
TI  - Single-shot electronic optical activity interferometry: power and phase
      fluctuation-free measurement.
AB  - We demonstrate that a single-pulse characterization of electronic optical
      activity-free induction decay, which carries information on both circular
      dichroism and optical rotatory dispersion, is experimentally feasible. Employing
      a self-referencing scheme, we show that a highly reliable interferometric
      chiroptical measurement free from power and phase fluctuations is achievable on a
      shot-by-shot basis.

PMID- 22463409
TI  - Efficient single-photon frequency conversion using a Sagnac interferometer.
AB  - We propose a scheme for efficient optical frequency conversion at the single
      photon power level. The scheme exploits the quantum interference of single-photon
      states at a three-level quantum emitter coupled to a Sagnac interferometer. We
      show that this device can achieve single-photon frequency up- or down-conversion
      with near unity efficiency.

PMID- 22463398
TI  - Search for lepton number violating decays B+ -> pi- MU+ MU+ and B+ -> K- MU+ MU+.
AB  - A search is performed for the lepton number violating decay B+ -> h- MU+ MU+,
      where h- represents a K- or a pi-, using an integrated luminosity of 36  pb(-1)
      of data collected with the LHCb detector. The decay is forbidden in the standard
      model but allowed in models with a Majorana neutrino. No signal is observed in
      either channel and limits of B(B+ -> K- MU+ MU+) < 5.4*10(-8) and B(B+ -> pi- MU+
      MU+) < 5.8*10(-8) are set at the 95% confidence level. These improve the previous
      best limits by factors of 40 and 30, respectively.

PMID- 22463410
TI  - Normal contact stiffness of elastic solids with fractal rough surfaces.
AB  - Using the boundary element method, we calculate the normal interfacial stiffness
      and constriction resistance of two elastic bodies with randomly rough surfaces
      and varying fractal dimensions. The contact stiffness as a function of the
      applied normal force can be approximated by a power law, with an exponent varying
      from 0.51 to 0.77 for fractal dimensions varying from 2 to 3.

PMID- 22463411
TI  - Opacity and transport measurements reveal that dilute plasma models of
      sonoluminescence are not valid.
AB  - A strong interaction between a nanosecond laser and a 70 MUm radius
      sonoluminescing plasma is achieved. The overall response of the system results in
      a factor of 2 increase in temperature as determined by its spectrum. Images of
      the interaction reveal that light energy is absorbed and trapped in a region
      smaller than the sonoluminescence emitting region of the bubble for over 100 ns.
      We interpret this opacity and transport measurement as demonstrating that
      sonoluminescencing bubbles can be 1000 times more opaque than what follows from
      the Saha equation of statistical mechanics in the ideal plasma limit. To address
      this discrepancy, we suggest that the effects of strong Coulomb interactions are
      an essential component of a first principles theory of sonoluminescence.

PMID- 22463413
TI  - Formation of surface nanobubbles and the universality of their contact angles: a
      molecular dynamics approach.
AB  - We study surface nanobubbles using molecular dynamics simulation of ternary (gas,
      liquid, solid) systems of Lennard-Jones fluids. They form for a sufficiently low
      gas solubility in the liquid, i.e., for a large relative gas concentration. For a
      strong enough gas-solid attraction, the surface nanobubble is sitting on a gas
      layer, which forms in between the liquid and the solid. This gas layer is the
      reason for the universality of the contact angle, which we calculate from the
      microscopic parameters. Under the present equilibrium conditions the nanobubbles
      dissolve within less of a microsecond, consistent with the view that the
      experimentally found nanobubbles are stabilized by a nonequilibrium mechanism.

PMID- 22463412
TI  - Intrinsic nonlinear scale governs oscillations in rapid fracture.
AB  - When branching is suppressed, rapid cracks undergo a dynamic instability from a
      straight to an oscillatory path at a critical velocity v(c). In a systematic
      experimental study using a wide range of different brittle materials, we first
      show how the opening profiles of straight cracks scale with the size l(nl) of the
      nonlinear zone surrounding a crack's tip. We then show, for all materials tested,
      that v(c) is both a fixed fraction of the shear speed and, moreover, that the
      instability wavelength is proportional to l(nl). These findings directly verify
      recent theoretical predictions and suggest that the nonlinear zone is not
      passive, but rather is closely linked to rapid crack instabilities.

PMID- 22463414
TI  - Convection in multiphase fluid flows using lattice Boltzmann methods.
AB  - We present high-resolution numerical simulations of convection in multiphase
      flows (boiling) using a novel algorithm based on a lattice Boltzmann method. We
      first study the thermodynamical and kinematic properties of the algorithm. Then,
      we perform a series of 3D numerical simulations changing the mean properties in
      the phase diagram and compare convection with and without phase coexistence at
      Rayleigh number Ra~10(7). We show that in the presence of nucleating bubbles non
      Oberbeck-Boussinesq effects develop, the mean temperature profile becomes
      asymmetric, and heat-transfer and heat-transfer fluctuations are enhanced, at all
      Ra studied. We also show that small-scale properties of velocity and temperature
      fields are strongly affected by the presence of the buoyant bubble leading to
      high non-gaussian profiles in the bulk.

PMID- 22463415
TI  - Channeling of relativistic laser pulses, surface waves, and electron
      acceleration.
AB  - The interaction of a high-energy relativistic laser pulse with an underdense
      plasma is studied by means of 3-dimensional particle in cell simulations and
      theoretical analysis. For powers above the threshold for channeling, the laser
      pulse propagates as a single mode in an electron-free channel during a time of
      the order of 1 picosecond. The steep laser front gives rise to the excitation of
      a surface wave along the sharp boundaries of the ion channel. The surface wave
      first traps electrons at the channel wall and preaccelerates them to relativistic
      energies. These particles then have enough energy to be further accelerated in a
      second stage through an interplay between the acceleration due to the betatron
      resonance and the acceleration caused by the longitudinal part of the surface
      wave electric field. It is necessary to introduce this two-stage process to
      explain the large number of high-energy electrons observed in the simulations.

PMID- 22463416
TI  - Scattering of magnetic mirror trapped fast electrons by a shear Alfven wave.
AB  - Laboratory observations of enhanced loss of fast electrons trapped in a magnetic
      mirror geometry irradiated by shear Alfven waves (SAW) are reported. A population
      of runaway electrons generated by second harmonic electron-cyclotron-resonance
      heating, as evidenced by the production of hard x rays with energy up to 3 MeV,
      is subjected to SAW launched with a rotating magnetic field antenna. It is
      observed that the SAW dramatically affect the trapped fast electrons and scatter
      them out of the magnetic mirror despite any obvious resonance. The results could
      have implications on the techniques of artificial reduction of energetic
      electrons in the inner radiation belt.

PMID- 22463417
TI  - Cavitating Langmuir turbulence in the terrestrial aurora.
AB  - Langmuir cavitons have been artificially produced in Earth's ionosphere, but
      evidence of naturally occurring cavitation has been elusive. By measuring and
      modeling the spectra of electrostatic plasma modes, we show that natural
      cavitating, or strong, Langmuir turbulence does occur in the ionosphere, via a
      process in which a beam of auroral electrons drives Langmuir waves, which in turn
      produce cascading Langmuir and ion-acoustic excitations and cavitating Langmuir
      turbulence. The data presented here are the first direct evidence of cavitating
      Langmuir turbulence occurring naturally in any space or astrophysical plasma.

PMID- 22463418
TI  - High-power terahertz-range planar gyrotrons with transverse energy extraction.
AB  - To increase the output power of terahertz gyrotrons to several hundred kilowatts,
      we suggest using a planar geometry of interaction space with a sheet electron
      beam and transverse energy extraction. An advantage of this scheme in comparison
      with conventional cylindrical geometry is the possibility to ensure effective
      mode selection over the open transverse coordinate in combination with radiation
      outcoupling that leads to a substantial reduction of Ohmic losses. Similar to
      unstable resonators in optics for further growth of the radiation power it is
      beneficial to introduce waveguide tapering.

PMID- 22463419
TI  - Liquid ground state, gap, and excited states of a strongly correlated spin chain.
AB  - We present an exact solution of an experimentally realizable and strongly
      interacting one-dimensional spin system which is a limiting case of a quantum
      Ising model with long range interaction in a transverse and longitudinal field.
      Pronounced quantum fluctuations lead to a strongly correlated liquid ground
      state. For open boundary conditions the ground state manifold consists of four
      degenerate sectors whose quantum numbers are determined by the orientation of the
      edge spins. Explicit expressions for the entanglement properties, the exact
      excitation gap, as well as the exact wave functions for a couple of excited
      states are analytically derived and discussed. We outline how this system can be
      experimentally realized in a lattice gas of Rydberg atoms.

PMID- 22463420
TI  - Staircaselike suppression of supersolidity under rotation.
AB  - There are a number of distinct signatures of superfluids, one of which is the
      appearance of quantized vortices. There have been some attempts to understand the
      putative supersolid 4He in the vortex framework, but no conclusive evidence that
      supports the existence of the vortices has been reported. Here, we investigate
      the rotation velocity dependence of the torsional oscillation of solid 4He at
      various temperatures. The velocity sweep reveals intriguing periodic
      staircaselike features below about 300 mK. The staircase patterns show remarkable
      periodicity, and we interpret these patterns as a consequence of vortex
      injection. However, there are some features that cannot be accounted for with
      simple injection of vortices into superfluid, and further investigation is
      required.

PMID- 22463421
TI  - Narrowing the length distribution of Ge nanowires.
AB  - Synthesis of nanostructures of uniform size is fundamental because the size
      distribution directly affects their physical properties. We present experimental
      data demonstrating a narrowing effect on the length distribution of Ge nanowires
      synthesized by the Au-catalyzed molecular beam epitaxy on Si substrates. A
      theoretical model is developed that is capable of describing this puzzling
      behavior. It is demonstrated that the direction of the diffusion flux of sidewall
      adatoms is size dependent and has a major effect on the growth rate of
      differently sized nanowires. We also show that there exists a fundamental
      limitation on the maximum nanowire length that can be achieved by molecular beam
      epitaxy where the direction of the beam is close to the growth axis.

PMID- 22463422
TI  - Dispersion interactions and vibrational effects in ice as a function of pressure:
      a first principles study.
AB  - We present a first principles theoretical framework that accurately accounts for
      several properties of ice, over a wide pressure range. In particular, we show
      that, by using a recently developed nonlocal van der Waals functional and by
      taking into account hydrogen zero point motion, one can properly describe the
      zero temperature equation of state, the vibrational spectra, and the dielectric
      properties of ice at low pressure and of ice VIII, a stable phase between 2 and
      60 GPa. While semilocal density functionals yield a transition pressure from ice
      XI to VIII that is overestimated by almost an order of magnitude, we find good
      agreement with experiments when dispersion forces are taken into account. Zero
      point energy contributions do not alter the computed transition pressure, but
      they affect structural properties, including equilibrium volumes and bulk moduli.

PMID- 22463423
TI  - Heterogeneous and anisotropic dynamics of a 2D gel.
AB  - We report x-ray photon correlation spectroscopy (XPCS) results on bidimensional
      (2D) gels formed by a Langmuir monolayer of gold nanoparticles. The system allows
      an experimental determination of the fourth order time correlation function,
      which is compared to the usual second order correlation function and to the
      mechanical response measured on macroscopic scale. The observed dynamics is
      anisotropic, heterogeneous and superdiffusive on the nanoscale. Different time
      scales, associated with fast heterogeneous dynamics inside 2D cages and slower
      motion of larger parts of the film, can be identified from the correlation
      functions. The XPCS results are discussed in view of other experimental results
      and models of three-dimensional gel dynamics.

PMID- 22463401
TI  - Measurement of the CP-violating phase phi(s) in the decay B(s)(0) -> J/psiphi.
AB  - We present a measurement of the time-dependent CP-violating asymmetry in B(s)(0) 
      > J/psiphi decays, using data collected with the LHCb detector at the LHC. The
      decay time distribution of B(s)(0) -> J/psiphi is characterized by the decay
      widths Gamma(H) and Gamma(L) of the heavy and light mass eigenstates,
      respectively, of the B(s)(0) - B(s)(0) system and by a CP-violating phase phi(s).
      In a sample of about 8500 B(s)(0) -> J/psiphi events isolated from 0.37  fb(-1)
      of pp collisions at sqrt[s] = 7  TeV, we measure phi(s) = 0.15 +/- 0.18(stat) +/-
      0.06(syst)  rad. We also find an average B(s)(0) decay width Gamma(s) = (Gamma(L)
      + Gamma(H))/2 = 0.657 +/- 0.009(stat) +/- 0.008(syst)  ps(-1) and a decay width
      difference DeltaGamma(s) = Gamma(L) - Gamma(H) = 0.123 +/- 0.029(stat) +/-
      0.011(syst)  ps(-1). Our measurement is insensitive to the transformation
      (phi(s),DeltaGamma(s)) ? (pi - phi(s), -DeltaGamma(s)).

PMID- 22463424
TI  - Thermomolecular orientation of nonpolar fluids.
AB  - We investigate the response of molecular fluids to temperature gradients. Using
      nonequilibrium molecular dynamics computer simulations we show that nonpolar
      diatomic fluids adopt a preferred orientation as a response to a temperature
      gradient. We find that the magnitude of this thermomolecular orientation effect
      is proportional to the strength of the temperature gradient and the degree of
      molecular anisotropy, as defined by the different size or mass of the molecular
      atomic sites. We show that the preferred orientation of the molecules follows the
      same trends observed in the Soret effect of binary mixtures. We argue this is a
      general effect that should be observed in a wide range of length scales.

PMID- 22463426
TI  - Interfacial alloy hydride destabilization in Mg/Pd thin films.
AB  - Recently, a large increase in the equilibrium hydrogen pressure has been reported
      for MG thin films capped with a Pd layer. We show that this increase is due to
      intermixing of Mg and Pd, as opposed to a strain effect as previously claimed.
      Transmission electron microscopy and depth profiling x-ray photoemission
      spectroscopy are used to directly measure interfacial intermixing between Mg and
      Pd, and we find that intermixing and equilibrium hydrogen pressure both increase
      with annealing. We present a thermodynamic model of the effect of alloying on
      equilibrium pressure, and find that the observed equilibrium pressure increase is
      consistent with the observed thickness of the intermixed region, which is of the
      order of a few nm. We also show that stress measured during hydrogenation
      corresponds to a negligible increase in equilibrium pressure.

PMID- 22463427
TI  - Commensurate registry and chemisorption at a hetero-organic interface.
AB  - We present evidence for a partly chemisorptive bonding between single monolayers
      of copper-II-phthalocyanine (CuPc) and 3,4,9,10-perylene-tetracarboxylic
      dianhydride (PTCDA) that are stacked on Ag(111). A commensurate registry between
      the two molecular layers and the substrate, i.e., a common crystallographic
      lattice for CuPc and PTCDA films as well as for the Ag(111) surface, indicates
      that the growth of the upper layer is dominated by the structure of the lower.
      Photoemission spectroscopy clearly reveals a gradual filling of the lowest
      unoccupied molecular orbital of PTCDA due to CuPc adsorption, which proves the
      chemisorptive character.

PMID- 22463425
TI  - Forces between hydrophobic solids in concentrated aqueous salt solution.
AB  - Much research has focused on the discovery and description of long-ranged forces
      between hydrophobic solids immersed in water. Here we show that the force between
      high contact-angle solids in concentrated salt solution (1 M KCl) agrees very
      well with van der Waals forces calculated from Lifshitz theory for separations
      greater than 5 nm. The hydrophobic solids are octadecyltrichlorosilane-coated
      glass, with an advancing contact angle of 108 degrees . Thus, in 1 M salt
      solution, it is unnecessary to invoke the presence of a hydrophobic force at
      separations greater than 5 nm. Through measurement in salt solution, we avoid the
      necessity of accounting for large electrostatic forces that frequently occur in
      pure water and may obscure resolution of other forces.

PMID- 22463428
TI  - Nanoscale deformation of a liquid surface.
AB  - We study the interaction between a solid particle and a liquid interface. A
      semianalytical solution of the nonlinear equation that describes the interface
      deformation points out the existence of a bifurcation behavior for the apex
      deformation as a function of the distance. We show that the apex curvature obeys
      a simple power-law dependency on the deformation. Relationships between physical
      parameters disclose the threshold distance at which the particle can approach the
      liquid before capillarity provokes a "jump to contact." A prediction of the
      interface original position before deformation takes place, as well as the
      attraction force measured by an approaching probe, are produced. The results of
      our analysis agree with the force curves obtained from atomic force microscopy
      experiments over a liquid puddle.

PMID- 22463430
TI  - Topological quantum phase transition in 5d transition metal oxide Na2IrO3.
AB  - We predict a quantum phase transition from normal to topological insulators in
      the 5d transition metal oxide Na2IrO3, where the transition can be driven by the
      change of the long-range hopping and trigonal crystal field terms. From the first
      principles-derived tight-binding Hamiltonian, we determine the phase boundary
      through the parity analysis. In addition, our first-principles calculations for
      Na2IrO3 model structures show that the interlayer distance can be an important
      parameter for the existence of a three-dimensional strong topological insulator
      phase. Na2IrO3 is suggested to be a candidate material which can have both a
      nontrivial topology of bands and strong electron correlations.

PMID- 22463429
TI  - Adsorbate induced restructuring of TiO2(011)-(2*1) leads to one-dimensional
      nanocluster formation.
AB  - Metal oxide surfaces have been thought to be fairly rigid. On the example of
      rutile TiO2(011) we show that this is not necessarily the case. This surface
      restructures by interacting with molecules. The synergic effect of adsorbates
      causes a strictly directional reorganization of the substrate, which results in
      one-dimensional adsorbate cluster formation. The increase in the surface energy
      of the restructured surface is compensated for by the larger molecular adsorption
      energy. The reversible change of the surface structure suggests a dynamic surface
      that may change its properties in response to adsorbed molecules.

PMID- 22463431
TI  - Ultrastrong coupling regime and plasmon polaritons in parabolic semiconductor
      quantum wells.
AB  - Ultrastrong coupling is studied in a modulation-doped parabolic potential well
      coupled to an inductance-capacitance resonant circuit. In this system, in
      accordance to Kohn's theorem, strong reduction of the energy level separation
      caused by the electron-electron interaction compensates the depolarization shift.
      As a result, a very large ratio of 27% of the Rabi frequency to the center
      resonance frequency as well as a polariton gap of width 2pi * 670  GHz are
      observed, suggesting parabolic quantum wells as the system of choice in order to
      explore the ultrastrong coupling regime.

PMID- 22463432
TI  - Universal probes of two-dimensional topological insulators: dislocation and pi
      flux.
AB  - We show that the pi flux and the dislocation represent topological observables
      that probe two-dimensional topological order through binding of the zero-energy
      modes. We analytically demonstrate that pi flux hosts a Kramers pair of zero
      modes in the topological Gamma (Berry phase Skyrmion at the zero momentum) and M
      (Berry phase Skyrmion at a finite momentum) phases of the M-B model introduced
      for the HgTe quantum spin Hall insulator. Furthermore, we analytically show that
      the dislocation acts as a pi flux, but only so in the M phase. Our numerical
      analysis confirms this through a Kramers pair of zero modes bound to a
      dislocation appearing in the M phase only, and further demonstrates the
      robustness of the modes to disorder and the Rashba coupling. Finally, we
      conjecture that by studying the zero modes bound to dislocations all
      translationally distinguishable two-dimensional topological band insulators can
      be classified.

PMID- 22463433
TI  - Connecting the reentrant insulating phase and the zero-field metal-insulator
      transition in a 2D hole system.
AB  - We present the transport and capacitance measurements of 10 nm wide GaAs quantum
      wells with hole densities around the critical point of the 2D metal-insulator
      transition (critical density p(c) down to 0.8 * 10(10)/cm2, r(s) ~ 36). For
      metallic hole density p(c) < p < p(c) + 0.15 * 10(10)/cm2, a reentrant insulating
      phase (RIP) is observed between the nu = 1 quantum Hall state and the zero-field
      metallic state and it is attributed to the formation of pinned Wigner crystal.
      Through studying the evolution of the RIP versus 2D hole density, we show that
      the RIP is incompressible and continuously connected to the zero-field insulator,
      suggesting a similar origin for these two phases.

PMID- 22463434
TI  - Electron-electron interaction in the magnetoresistance of graphene.
AB  - We investigate the magnetotransport in large area graphene Hall bars epitaxially
      grown on silicon carbide. In the intermediate field regime between weak
      localization and Landau quantization, the observed temperature-dependent
      parabolic magnetoresistivity is a manifestation of the electron-electron
      interaction. We can consistently describe the data with a model for diffusive
      (magneto)transport that also includes magnetic-field-dependent effects
      originating from ballistic time scales. We find an excellent agreement between
      the experimentally observed temperature dependence of magnetoresistivity and the
      theory of electron-electron interaction in the diffusive regime. We can further
      assign a temperature-driven crossover to the reduction of the multiplet modes
      contributing to electron-electron interaction from 7 to 3 due to intervalley
      scattering. In addition, we find a temperature-independent ballistic contribution
      to the magnetoresistivity in classically strong magnetic fields.

PMID- 22463435
TI  - Local charge and spin currents in magnetothermal landscapes.
AB  - A scannable laser beam is used to generate local thermal gradients in metallic
      (Co2FeAl) or insulating (Y3Fe5O12) ferromagnetic thin films. We study the
      resulting local charge and spin currents that arise due to the anomalous Nernst
      effect (ANE) and the spin Seebeck effect (SSE), respectively. In the local ANE
      experiments, we detect the voltage in the Co2FeAl thin film plane as a function
      of the laser-spot position and external magnetic field magnitude and orientation.
      The local SSE effect is detected in a similar fashion by exploiting the inverse
      spin Hall effect in a Pt layer deposited on top of the Y3Fe5O12. Our findings
      establish local thermal spin and charge current generation as well as spin
      caloritronic domain imaging.

PMID- 22463436
TI  - How to distinguish between specular and retroconfigurations for Andreev
      reflection in graphene rings.
AB  - We numerically investigate Andreev reflection in a graphene ring with one normal
      conducting and one superconducting lead by solving the Bogoliubov-de Gennes
      equation within the Landauer-Buttiker formalism. By tuning chemical potential and
      bias voltage, it is possible to switch between regimes where electron and hole
      originate from the same band (retroconfiguration) or from different bands
      (specular configuration) of the graphene dispersion, respectively. We find that
      the dominant contributions to the Aharonov-Bohm conductance oscillations in the
      subgap transport are of period h/2e in retroconfiguration and of period h/e in
      specular configuration, confirming the predictions obtained from a qualitative
      analysis of interfering scattering paths. Because of the robustness against
      disorder and moderate changes to the system, this provides a clear signature to
      distinguish both types of Andreev reflection processes in graphene.

PMID- 22463437
TI  - Structure selection based on high vertical electron affinity for TiO2 clusters.
AB  - We study the structure and electronic properties of (TiO2)(2-10) clusters by
      using basin hopping based on density functional theory, combined with many-body
      perturbation theory. We show that in photoemission experiments performed on
      anions isomers with high electron affinity are selectively observed rather than
      those with the lowest energy. These isomers possess a highly reactive Ti3+ site.
      The selectivity for highly reactive clusters may be exploited for applications in
      catalysis.

PMID- 22463438
TI  - Transformation-optics description of nonlocal effects in plasmonic
      nanostructures.
AB  - We develop an insightful transformation-optics approach to investigate the impact
      that nonlocality has on the optical properties of plasmonic nanostructures. The
      light-harvesting performance of a dimer of touching nanowires is studied by using
      the hydrodynamical Drude model, which reveals nonlocal resonances not predicted
      by previous local calculations. Our method clarifies the interplay between
      radiative and nonlocal effects in this nanoparticle configuration, which enables
      us to elucidate the optimum size that maximizes its absorption and field
      enhancement capabilities.

PMID- 22463439
TI  - Spin splitting unconstrained by electron pairing: the spin-vibronic states.
AB  - Spin splitting of individual vibronic states was observed in a single molecule
      where all the electrons are paired, as well as a molecule with one extra electron
      injected. This observation was made possible by the use of a scanning tunneling
      microscope capable of reaching ~800  mK in a magnetic field up to 9 T and the
      sharpness of the vibronic states, ~1  meV. These conditions also led to the
      resolution of spectral diffusion caused by minute fluctuations at the probing
      location of the molecule.

PMID- 22463440
TI  - Magnetoresistance measurements of graphene at the charge neutrality point.
AB  - We report on transport measurements of the insulating state that forms at the
      charge neutrality point of graphene in a magnetic field. Using both conventional
      two-terminal measurements, sensitive to bulk and edge conductance, and Corbino
      measurements, sensitive only to the bulk conductance, we observed a vanishing
      conductance with increasing magnetic fields. By examining the resistance changes
      of this insulating state with varying perpendicular and in-plane fields, we probe
      the spin-active components of the excitations in total fields of up to 45 T. Our
      results indicate that the nu=0 quantum Hall state in single layer graphene is not
      spin-polarized.

PMID- 22463441
TI  - Coherent frequency conversion in a superconducting artificial atom with two
      internal degrees of freedom.
AB  - By adding a large inductance in a dc-SQUID phase qubit loop, one decouples the
      junctions' dynamics and creates a superconducting artificial atom with two
      internal degrees of freedom. In addition to the usual symmetric plasma mode (s
      mode) which gives rise to the phase qubit, an antisymmetric mode (a mode)
      appears. These two modes can be described by two anharmonic oscillators with
      eigenstates |ns> and |na> for the s and a mode, respectively. We show that a
      strong nonlinear coupling between the modes leads to a large energy splitting
      between states |0s,1a> and |2s,0a>. Finally, coherent frequency conversion is
      observed via free oscillations between the states |0s,1a> and |2s,0a>.

PMID- 22463442
TI  - Friedel-like oscillations from interstitial iron in superconducting
      Fe(1+y)Te0.62Se0.38.
AB  - Using polarized and unpolarized neutron scattering, we show that interstitial Fe
      in superconducting Fe(1+y)Te(1-x)Se(x) induces a magnetic Friedel-like
      oscillation that diffracts at Q?=(1/2 0) and involves >50 neighboring Fe sites.
      The interstitial >2MU(B) moment is surrounded by compensating ferromagnetic four
      spin clusters that may seed double stripe ordering in Fe(1+y)Te. A semimetallic
      five-band model with (1/2 1/2) Fermi surface nesting and fourfold symmetric
      superexchange between interstitial Fe and two in-plane nearest neighbors largely
      accounts for the observed diffraction.

PMID- 22463443
TI  - Highly confined spin-polarized two-dimensional electron gas in SrTiO3/SrRuO3
      superlattices.
AB  - We report first-principles characterization of the structural and electronic
      properties of (SrTiO3)5/(SrRuO3)1 superlattices. We show that the system exhibits
      a spin-polarized two-dimensional electron gas, extremely confined to the 4d
      orbitals of Ru in the SrRuO3 layer. Every interface in the superlattice behaves
      as a minority-spin half-metal ferromagnet, with a magnetic moment of
      MU=2.0MU(B)/SrRuO3 unit. The shape of the electronic density of states, half
      metallicity, and magnetism are explained in terms of a simplified tight-binding
      model, considering only the t(2g) orbitals plus (i) the bidimensionality of the
      system and (ii) strong electron correlations.

PMID- 22463444
TI  - Increased superconducting transition temperature of a niobium thin film proximity
      coupled to gold nanoparticles using linking organic molecules.
AB  - The superconducting critical temperature, T(C), of thin Nb films is significantly
      modified when gold nanoparticles (NPs) are chemically linked to the Nb film, with
      a consistent enhancement when using 3 nm long disilane linker molecules. The T(C)
      increases by up to 10% for certain linker length and NP size. No change is
      observed when the nanoparticles are physisorbed with nonlinking molecules.
      Electron tunneling spectra acquired on the linked NPs below T(C) typically
      exhibit zero-bias peaks. We attribute these results to a pairing mechanism
      coupling electrons in the Nb and the NPs, mediated by the organic linkers.

PMID- 22463445
TI  - Majorana fermions and exotic surface Andreev bound states in topological
      superconductors: application to Cu(x)Bi2Se3.
AB  - The recently discovered superconductor Cu(x)Bi2Se3 is a candidate for three
      dimensional time-reversal-invariant topological superconductors, which are
      predicted to have robust surface Andreev bound states hosting massless Majorana
      fermions. In this work, we analytically and numerically find the linearly
      dispersing Majorana fermions at k=0, which smoothly evolve into a new branch of
      gapless surface Andreev bound states near the Fermi momentum. The latter is a new
      type of Andreev bound states resulting from both the nontrivial band structure
      and the odd-parity pairing symmetry. The tunneling spectra of these surface
      Andreev bound states agree well with a recent point-contact spectroscopy
      experiment [S. Sasaki et al., Phys. Rev. Lett. 107, 217001 (2011)] and yield
      additional predictions for low temperature tunneling and photoemission
      experiments.

PMID- 22463446
TI  - Broadly tunable subterahertz emission from internal branches of the current
      voltage characteristics of superconducting Bi2Sr2CaCu2O(8+delta) single crystals.
AB  - Continuous, coherent subterahertz radiation arises when a dc voltage is applied
      across a stack of the many intrinsic Josephson junctions in a
      Bi2Sr2CaCu2O(8+delta) single crystal. The active junctions produce an equal
      number of I-V characteristic branches. Each branch radiates at a slightly tunable
      frequency obeying the Josephson relation. The overall output is broadly tunable
      and nearly independent of heating effects and internal cavity frequencies.
      Amplification by a surrounding external cavity to allow for the development of a
      useful high-power source is proposed.

PMID- 22463447
TI  - Local quantum criticality of an iron-pnictide tetrahedron.
AB  - Motivated by the close correlation between transition temperature (T(c)) and the
      tetrahedral bond angle of the As-Fe-As layer observed in the iron-based
      superconductors, we study the interplay between spin and orbital physics of an
      isolated iron-arsenide tetrahedron embedded in a metallic environment. Whereas
      the spin-Kondo effect is suppressed to low temperatures by Hund's coupling, the
      orbital degrees of freedom are expected to quantum mechanically quench at high
      temperatures, giving rise to an overscreened, non-Fermi liquid ground state.
      Translated into a dense environment, this critical state may play an important
      role in the superconductivity of these materials.

PMID- 22463448
TI  - Chiral magnetic soliton lattice on a chiral helimagnet.
AB  - Using Lorenz microscopy and small-angle electron diffraction, we directly present
      that the chiral magnetic soliton lattice (CSL) continuously evolves from a chiral
      helimagnetic structure in small magnetic fields in Cr(1/3)NbS2. An incommensurate
      CSL undergoes a phase transition to a commensurate ferromagnetic state at the
      critical field strength. The period of a CSL, which exerts an effective potential
      for itinerant spins, is tuned by simply changing the field strength. Chiral
      magnetic orders observed do not exhibit any structural dislocation, indicating
      their high stability and robustness in Cr(1/3)NbS2.

PMID- 22463449
TI  - Vortex domain walls in helical magnets.
AB  - We show that helical magnets exhibit a nontrivial type of domain wall consisting
      of a regular array of vortex lines, except for a few distinguished orientations.
      This result follows from topological consideration and is independent of the
      microscopic models. We used simple models to calculate the shape and energetics
      of vortex walls in centrosymmetric and noncentrosymmetric crystals. Vortices are
      strongly anisotropic, deviating from the conventional Berezinskii-Kosterlitz
      Thouless form. The width of the domain walls depend only weakly on the magnetic
      anisotropy, in contrast to ferromagnets and antiferromagnets. We show that vortex
      walls can be driven by external currents and in multiferroics also by electric
      fields.

PMID- 22463450
TI  - Chemical engineering of molecular qubits.
AB  - We show that the electron spin phase memory time, the most important property of
      a molecular nanomagnet from the perspective of quantum information processing,
      can be improved dramatically by chemically engineering the molecular structure to
      optimize the environment of the spin. We vary systematically each structural
      component of the class of antiferromagnetic Cr(7)Ni rings to identify the sources
      of decoherence. The optimal structure exhibits a phase memory time exceeding 15 
      MUs.

PMID- 22463451
TI  - Magnetism and antiferroelectricity in MgB6.
AB  - We report on a density functional theory study demonstrating the coexistence of
      weak ferromagnetism and antiferroelectricity in boron-deficient MgB6. A boron
      vacancy produces an almost one dimensional extended molecular orbital, which is
      responsible for the magnetic moment formation. Then, long-range magnetic order
      can emerge from the overlap of such orbitals above percolation threshold.
      Although there is a finite density of states at the Fermi level, the localized
      nature of the charge density causes an inefficient electron screening. We find
      that the Mg2+ ions can displace from the center of their cubic cage, thus
      generating electrical dipoles. In the ground state these order in an
      antiferroelectric configuration. If proved experimentally, this will be the first
      material without d or f electrons displaying the coexistence of magnetic and
      electric order.

PMID- 22463452
TI  - Magnetization reversal of individual Co nanoislands.
AB  - We investigate the magnetization reversal of individual Co islands on Cu(111) in
      the size range of N=700 to 18,000 atoms by spin-polarized scanning tunneling
      microscopy at 8 K. The switching field H(sw) changes with island size in a
      nonmonotonic manner: it increases with island size and reaches a maximum value of
      2.4 T at N=5500 atoms, and it decreases for larger islands. We extract the energy
      barrier for magnetization reversal as a function of island size. The maximum
      H(sw) corresponds to an energy barrier of 1 eV. Our results elucidate a crossover
      of the magnetization reversal from an exchange-spring behavior to domain wall
      formation with increasing size at around 7500 atoms.

PMID- 22463453
TI  - Probing single-charge fluctuations at a GaAs/AlAs interface using laser
      spectroscopy on a nearby InGaAs quantum dot.
AB  - We probe local charge fluctuations in a semiconductor via laser spectroscopy on a
      nearby self-assembled quantum dot. We demonstrate that the quantum dot is
      sensitive to changes in the local environment at the single-charge level. By
      controlling the charge state of localized defects, we are able to infer the
      distance of the defects from the quantum dot with +/-5  nm resolution. The
      results identify and quantify the main source of charge noise in the commonly
      used optical field-effect devices.

PMID- 22463454
TI  - Measuring relative grain-boundary energies in block-copolymer microstructures.
AB  - The (relative) energies of symmetric tilt grain boundaries in a strongly
      segregated lamellar block copolymer are determined by analysis of the dihedral
      angles at grain-boundary triple junctions. The analysis reveals two regimes: at
      low and intermediate misorientations (corresponding to a tilt-angle range
      0<=theta<=85 degrees ) the grain-boundary energy is found to depend on the tilt
      angle as E(theta)~theta(x), with 2.5>x>=0. At large misorientations the grain
      boundary energy is found to be independent (within the experimental uncertainty)
      of the angle of tilt. The transition between the two scaling regimes is
      accompanied by the transition of the grain-boundary structure from the chevron to
      the omega morphology. Grain-boundary energy and frequency are found to be
      inversely related, thus suggesting boundary energy to be an important parameter
      during grain coarsening in block-copolymer microstructures, as it is in inorganic
      polycrystalline microstructures.

PMID- 22463455
TI  - Nucleation and crystal growth in sheared granular sphere packings.
AB  - We investigate the nucleation of ordered phases, their symmetries, and
      distributions in dense frictional hard sphere packings as a function of particle
      volume fraction phi, by imposing cyclic shear and constant applied pressure
      conditions. We show, with internal imaging, that the nucleating crystallites in
      the bulk consist of 10-60 spheres with hexagonal close packed (hcp) order and
      nonspherical shape, that are oriented preferentially along the shear axis. Above
      phi=0.62+/-0.005, crystallites with face centered cubic (fcc) order are observed
      with increasing probability, and ordered domains grow rapidly. A polycrystalline
      phase with domains of fcc and hcp order is observed after hundreds of thousands
      of shear cycles.

PMID- 22463456
TI  - Polymer dynamics, fluorescence correlation spectroscopy, and the limits of
      optical resolution.
AB  - In recent years, fluorescence correlation spectroscopy has been increasingly
      applied for the study of polymer dynamics on the nanometer scale. The core idea
      is to extract, from a measured autocorrelation curve, an effective mean-square
      displacement function that contains information about the underlying
      conformational dynamics. This Letter presents a fundamental study of the
      applicability of fluorescence correlation spectroscopy for the investigation of
      nanoscale conformational and diffusional dynamics. We find that fluorescence
      correlation spectroscopy cannot reliably elucidate processes on length scales
      much smaller than the resolution limit of the optics used and that its improper
      use can yield spurious results for the observed dynamics.

PMID- 22463457
TI  - Transmembrane helix assembly by window exchange umbrella sampling.
AB  - A method of window exchange umbrella sampling molecular dynamics simulation is
      employed for transmembrane helix assembly. An analytical expression for the
      average acceptance probability between neighboring windows is derived and
      combined with the first passage time optimization method to predetermine a
      parameter set in an optimal range. With the parameter set, the method provides a
      substantially more efficient sampling of helix-helix interfaces together with the
      potential of mean force along the helix-helix distance of a transmembrane helix
      dimer model, compared to the umbrella sampling method.

PMID- 22463458
TI  - Unidirectional pinning and hysteresis of spatially discordant alternans in
      cardiac tissue.
AB  - Spatially discordant alternans is a widely observed pattern of voltage and
      calcium signals in cardiac tissue that can precipitate lethal cardiac arrhythmia.
      Using spatially coupled iterative maps of the beat-to-beat dynamics, we explore
      this pattern's dynamics in the regime of a calcium-dominated period-doubling
      instability at the single-cell level. We find a novel nonlinear bifurcation
      associated with the formation of a discontinuous jump in the amplitude of calcium
      alternans at nodes separating discordant regions. We show that this jump
      unidirectionally pins nodes by preventing their motion away from the pacing site
      following a pacing rate decrease but permitting motion towards this site
      following a rate increase. This unidirectional pinning leads to strongly history
      dependent node motion that is strongly arrhythmogenic.

PMID- 22463459
TI  - Reliability of frequency and amplitude decoding in gene regulation.
AB  - In biochemical signaling, information is often encoded in oscillatory signals.
      However, the advantages of such a coding strategy over an amplitude-encoding
      scheme of constant signals remain unclear. Here we study the dynamics of a simple
      model gene promoter in response to oscillating and constant transcription factor
      signals. We find that in biologically relevant parameter regimes an oscillating
      input can produce a more constant protein level than a constant input. Our
      results suggest that oscillating signals may be used to minimize noise in gene
      regulation.

PMID- 22463460
TI  - Validity of the law of mass action in three-dimensional coagulation processes.
AB  - Diffusion-limited reactions are studied in detail on the classical coalescing
      process. We demonstrate how, with the aid of a recent renormalization group
      approach, fluctuations can be integrated systematically. We thereby obtain an
      exact relation between the microscopic physics (lattice structure and particle
      shape and size) and the macroscopic decay rate in the law of mass action.
      Moreover, we find a strong violation of the law of mass action. The corresponding
      term in the kinetic equations originates in long-wavelength fluctuations and is a
      universal function of the macroscopic decay rate.

PMID- 22463461
TI  - Strain stiffening in random packings of entangled granular chains.
AB  - Random packings of granular chains are presented as a model system to investigate
      the contribution of entanglements to strain stiffening. The chain packings are
      sheared in uniaxial compression experiments. For short chain lengths, these
      packings yield when the shear stress exceeds the scale of the confining pressure,
      similar to granular packings of unconnected particles. In contrast, packings of
      chains which are long enough to form loops exhibit strain stiffening, in which
      the effective stiffness of the material increases with strain, similar to many
      polymer materials. The latter packings can sustain stresses orders-of-magnitude
      greater than the confining pressure, and do not yield until the chain links
      break. X-ray tomography measurements reveal that the strain-stiffening packings
      contain system-spanning clusters of entangled chains.

PMID- 22463462
TI  - Gel phase vesicles buckle into specific shapes.
AB  - Osmotic deflation of giant vesicles in the rippled gel phase P(beta') gives rise
      to a large variety of novel faceted shapes. These shapes are also found from a
      numerical approach by using an elastic surface model. A shape diagram is proposed
      based on the model that accounts for the vesicle size and ratios of three
      mechanical constants: in-plane shear elasticity and compressibility (usually
      neglected) and out-of-plane bending of the membrane. The comparison between
      experimental and simulated vesicle morphologies reveals that they are governed by
      a typical elasticity length, of the order of 1   MUm, and must be described with
      a large Poisson's ratio.

PMID- 22463463
TI  - Interspecific competition underlying mutualistic networks.
AB  - Multiple classes of interactions may exist affecting one another in a given
      system. For the mutualistic networks of plants and pollinating animals, it has
      been known that the degree distribution is broad but often deviates from power
      law form more significantly for plants than animals. To illuminate the origin of
      such asymmetry, we study a model network in which links are assigned under
      generalized preferential-selection rules between two groups of nodes and find the
      sensitive dependence of the resulting connectivity pattern on the model
      parameters. The nonlinearity of preferential selection can come from
      interspecific interactions among animals and among plants. The model-based
      analysis of real-world mutualistic networks suggests that a new animal determines
      its partners not only by their abundance but also under the competition with
      existing animal species, which leads to the stretched-exponential degree
      distributions of plants.

PMID- 22463466
TI  - Resonance Raman spectra of a complex containing the rhodium-iron bond.

PMID- 22463465
TI  - Inequities in maternal and child health outcomes and interventions in Ghana.
AB  - BACKGROUND: With the date for achieving the targets of the Millennium Development
      Goals (MDGs) approaching fast, there is a heightened concern about equity, as
      inequities hamper progress towards the MDGs. Equity-focused approaches have the
      potential to accelerate the progress towards achieving the health-related MDGs
      faster than the current pace in a more cost-effective and sustainable manner.
      Ghana's rate of progress towards MDGs 4 and 5 related to reducing child and
      maternal mortality respectively is less than what is required to achieve the
      targets. The objective of this paper is to examine the equity dimension of child
      and maternal health outcomes and interventions using Ghana as a case study.
      METHODS: Data from Ghana Demographic and Health Survey 2008 report is analyzed
      for inequities in selected maternal and child health outcomes and interventions
      using population-weighted, regression-based measures: slope index of inequality
      and relative index of inequality. RESULTS: No statistically significant
      inequities are observed in infant and under-five mortality, perinatal mortality,
      wasting and acute respiratory infection in children. However, stunting,
      underweight in under-five children, anaemia in children and women, childhood
      diarrhoea and underweight in women (BMI < 18.5) show inequities that are to the
      disadvantage of the poorest. The rates significantly decrease among the
      wealthiest quintile as compared to the poorest. In contrast, overweight (BMI 25
      29.9) and obesity (BMI >= 30) among women reveals a different trend - there are
      inequities in favour of the poorest. In other words, in Ghana overweight and
      obesity increase significantly among women in the wealthiest quintile compared to
      the poorest. With respect to interventions: treatment of diarrhoea in children,
      receiving all basic vaccines among children and sleeping under ITN (children and
      pregnant women) have no wealth-related gradient. Skilled care at birth,
      deliveries in a health facility (both public and private), caesarean section, use
      of modern contraceptives and intermittent preventive treatment for malaria during
      pregnancy all indicate gradients that are in favour of the wealthiest. The
      poorest use less of these interventions. Not unexpectedly, there is more use of
      home delivery among women of the poorest quintile. CONCLUSION: Significant
      Inequities are observed in many of the selected child and maternal health
      outcomes and interventions. Failure to address these inequities vigorously is
      likely to lead to non-achievement of the MDG targets related to improving child
      and maternal health (MDGs 4 and 5). The government should therefore give due
      attention to tackling inequities in health outcomes and use of interventions by
      implementing equity-enhancing measure both within and outside the health sector
      in line with the principles of Primary Health Care and the recommendations of the
      WHO Commission on Social Determinants of Health.

PMID- 22463464
TI  - Transplantation for complex congenital heart disease in adults: a subanalysis of
      the Spanish Heart Transplant Registry.
AB  - BACKGROUND: Congenital heart diseases (CHDs) have high infant mortality in their
      severe forms. When adulthood is reached, a heart transplant (HTx) may be
      required. Spanish adult population transplanted for CHD was analyzed and compared
      with the most frequent causes of HTx and between different subgroups of CHD.
      MATERIALS AND METHODS: A total of 6048 patients (HTx 1984-2009) were included.
      Pediatric transplants (<15 yr), combined transplants, reHTx, and HTx for heart
      diseases other than idiopathic dilated cardiomyopathy (IDCM) and ischemic heart
      disease (IHD) were excluded. Total patients included: 3166 (IHD = 1888; IDCM =
      1223; CHD = 55). Subgroups were studied as follows: (1) single ventricle with
      pulmonary stenosis (n = 18), (2) single ventricle with tricuspid atresia and
      Glenn/Fontan surgery (n = 10), (3) congenitally corrected transposition of the
      great vessels (TGV) or with switch atrial surgery (n = 10), and (4) CHD with
      right ventricle overload (n = 17). RESULTS: Survival probability was different
      between groups (p = 0.0001). Post hoc analysis showed some differences between
      groups (CHD vs. IHD, p = 0.05; CHD vs. IDCM, p = 0.5; IHD vs. IDCM, p = 0.0001).
      Early mortality was different between CHD subgroups (group 1 = 19%, group 2 =
      40%, group 3 = 0%, group 4 = 29%; p < 0.001); however, overall mortality did not
      show differences between subgroups (p = 0.5). CONCLUSIONS: The percentage of
      Spanish adult HTx patients for CHD is low (1%). The survival curve is better than
      for other HTx causes (IHD). Nevertheless, early mortality was higher,
      particularly in some subgroups (Fontan).

PMID- 22463467
TI  - Local anesthesia and hydro-distension to facilitate cystic calculus removal in
      horses.
AB  - OBJECTIVE: To report a technique for improving surgical access to the bladder for
      removal of cystic calculi in male horses. STUDY DESIGN: Retrospective case
      series. ANIMALS OR SAMPLE POPULATION: Geldings (8) with cystic calculi. METHODS:
      After catheterization of the bladder through the penis, 100 mL 2% lidocaine
      hydrochloride solution was instilled. After 10 minutes, the bladder was distended
      with sterile, warmed Hartmann's solution to a pressure of ~ 40 cm H(2) O, using
      gravity feed. This was left in place until abdominal access was gained at
      surgery, then the fluid siphoned off via the catheter. RESULTS: Calculi were 3-11
      cm in diameter (median, 6 cm). Bladder capacity ranged from 1.4 to 2.5 L (median,
      1.8 L). Exteriorization time from placing a hand in the abdomen to having the
      bladder in a surgically accessible position was <5 minutes. CONCLUSION: The
      described technique facilitates exteriorization of the bladder for removal of
      cystic calculi.

PMID- 22463468
TI  - Doctoral education and the future of nursing.

PMID- 22463470
TI  - Pediatric migraine teaching for families.
AB  - PURPOSE: Child and family education regarding management of pediatric migraine is
      essential to reduce acute pain, prevent chronic daily migraine, and minimize the
      total number of headache attacks. This paper summarizes current evidence and
      provides a foundation for family teaching. CONCLUSIONS: Effective management of
      pediatric migraine can be achieved with a combination of individually tailored
      biobehavioral strategies, lifestyle modifications, and optimal scheduling of
      rescue and preventative pharmacologic treatment. PRACTICE IMPLICATIONS: Included
      are goal setting recommendations, common triggers, key comorbidities, lifestyle
      modifications, principles of pharmacologic management, commonly used naturopathic
      compounds, and a link to an online downloadable teaching handout.

PMID- 22463469
TI  - Health behaviors and mental health of students attending alternative high
      schools: a review of the research literature.
AB  - PURPOSE: The purpose of this review is to describe current knowledge about health
      risk behaviors and mental health among alternative high school students.
      CONCLUSIONS: Substance use, diet and/or physical activity, sexual-risk behaviors,
      mental health, and violence were reviewed. Students were described as
      marginalized youth facing significant social environmental challenges. Findings
      from 43 studies published from 1997-2010 suggested a high prevalence of health
      risk behaviors among alternative high school students. Very few studies were
      conducted by nurse researchers. Suggestions for future research include
      addressing social environmental factors, resiliency, and emotional/mental health
      outcomes. PRACTICE IMPLICATIONS: Alternative high schools offer a venue to
      conduct research and implement nursing interventions with high-risk, yet
      resilient, youth.

PMID- 22463471
TI  - Parents' management of children's pain at home after surgery.
AB  - PURPOSE: We tested home pain management for children for effects on pain
      intensity, analgesics administered, satisfaction, and use of healthcare services
      over 3 post-discharge days. DESIGN AND METHODS: In this quasi-experimental study
      with 108 children and their parents, we used the numeric rating scale or the
      Faces Pain Scale-Revised, calculated percentages of analgesics administered, and
      asked questions about expectations, satisfaction, and services. Between-group
      differences were tested with t-tests and analysis of variance. RESULTS: After
      home pain management for children, children reported moderate pain, and parents
      administered more analgesics on study days. Parents and children were satisfied;
      parents used few services. Written instructions and a brief interactive session
      were not sufficient to change parents' analgesic administration practices to
      relieve their children's pain. PRACTICE IMPLICATIONS: Further research is needed
      to develop and test effective education interventions to facilitate relief of
      children's postoperative pain.

PMID- 22463472
TI  - Educating diabetes camp counselors with a human patient simulator: a pilot study.
AB  - PURPOSE: The purpose of this study was to pilot test the feasibility and efficacy
      of a novel method of teaching camp counselors hypoglycemia management. DESIGN AND
      METHODS: During orientation, counselors were assigned to the experimental (n= 21)
      or control (n= 15) group and received hypoglycemia education. The experimental
      group received supplemental education with a human patient simulator (HPS).
      RESULTS: Baseline demographics, knowledge, and self-efficacy were similar between
      groups. The experimental group had a significantly larger gain in diabetes
      knowledge than the control group. Within-participant change in self-efficacy did
      not differ by group. We observed a significant effect modification, with larger
      treatment-related differences in the small subgroup with no previous diabetes
      exposure. PRACTICE IMPLICATIONS: This feasibility study demonstrated the ease of
      teaching diabetes management to camp counselors using HPS.

PMID- 22463473
TI  - Childcare health and health consultation curriculum: trends and future directions
      in nursing education.
AB  - PURPOSE: The purpose of this study was to identify graduate and undergraduate
      nursing courses in health and health consultation in childcare and early
      education, and faculty awareness and interest in federal resources. DESIGN AND
      METHODS: A questionnaire was sent electronically to 140 faculty in 45 schools of
      nursing. RESULTS: Fifty-nine faculty from 45 schools (42%) participated, and 80%
      reported at least one course related to childcare health and safety. Most faculty
      were not aware of federal initiatives to support childcare health and safety, and
      the role of nurse childcare health consultants; however, many were interested in
      receiving instructional materials. PRACTICE IMPLICATIONS: Utilizing federal
      resources to augment nursing education in childcare health and safety curriculum
      may strengthen the workforce of nurses providing health consultation to early
      childhood programs.

PMID- 22463474
TI  - An exploration of pediatric nurses' compliance with a medication checking and
      administration protocol.
AB  - PURPOSE: This study examined nurses' reported compliance with the medication
      administration protocol and explored reasons for noncompliance. DESIGN AND
      METHOD: A mixed-methods design incorporated a questionnaire (n= 72) and focus
      groups (n= 24). RESULTS: Differences were found between the level of experience
      and protocol compliance. Noncompliance was widespread in the checking of
      identification bands and double-checking medications. Key factors influencing
      compliance were ward culture, type of drug, familiarity with patient and drug,
      and workload. The reported realities of practice were found to influence
      compliance with the medication administration protocol. PRACTICE IMPLICATIONS:
      The discrepancies between protocol and practice in this setting underscore the
      need to more widely investigate compliance with medication administration
      protocols in other settings.

PMID- 22463475
TI  - Initial development and testing of a questionnaire of parental self-efficacy for
      enacting healthy lifestyles in their children.
AB  - PURPOSE: The purpose of this study was to develop and test a questionnaire to
      assess parental self-efficacy for enacting healthy diet and physical activity
      behaviors in their 6- to 11-year-old children. DESIGN AND METHODS: A 35-item
      questionnaire was developed and tested with 146 U.S. parents. RESULTS:
      Participant responses resulted in a 34-item questionnaire with two subscales
      (dietary behaviors and physical activity behaviors), which were valid and
      reliable in the study sample. PRACTICE IMPLICATIONS: This new measure will serve
      as a tool for the assessment of parental self-efficacy for enacting healthy
      lifestyles in their children 6-11 years old.

PMID- 22463476
TI  - Older adolescents' perceptions and intentions regarding Do-It-Yourself Genetic
      Assessment services.
AB  - PURPOSE: The purpose of this research was to investigate older adolescents'
      perceptions of Do-It-Yourself Genetic Assessment (DIYGA) services online and
      factors that influence their intentions to utilize DIYGA services. DESIGN AND
      METHODS: A convenience sample of 111 undergraduate students completed an online
      survey based on the Theory of Planned Behavior. RESULTS: Most respondents (80.4%)
      had not heard of DIYGA services. Predictors of intentions to use DIYGA services
      included attitudes, subjective norms, and perceived risk of developing a genetic
      disorder. PRACTICE IMPLICATIONS: Nurses are in a unique position to provide much
      needed education and guidance to adolescents about genetic testing, particularly
      given mass media sources were the primary sources of information among these
      adolescents.

PMID- 22463477
TI  - Disaster risk and children part I: why poverty-stricken populations are impacted
      most.

PMID- 22463478
TI  - Best practices for improving intervention fidelity that every nurse should know.

PMID- 22463480
TI  - Two-color DNA nanoprobe of intracellular dynamics.
AB  - We have developed a correlation microscopy technique to follow the dynamics of
      quantum dot labeled DNA within living cells. The temporal correlation functions
      of the labels reflect the fluctuations of the DNA nanoprobe as a result of its
      interactions with the cellular environment. They provide a sensitive measure for
      the length of the probe on the scale of a persistence length (~50 nm) and reveal
      strong nonthermal dynamics of the cell. These results pave the way for dynamic
      observations of DNA conformational changes in vivo.

PMID- 22463481
TI  - Characterisation of connective tissue from the hypertrophic skeletal muscle of
      myostatin null mice.
AB  - Myostatin is a potent inhibitor of muscle development. Genetic deletion of
      myostatin in mice results in muscle mass increase, with muscles often weighing
      three times their normal values. Contracting muscle transfers tension to skeletal
      elements through an elaborate connective tissue network. Therefore, the
      connective tissue of skeletal muscle is an integral component of the contractile
      apparatus. Here we examine the connective tissue architecture in myostatin null
      muscle. We show that the hypertrophic muscle has decreased connective tissue
      content compared with wild-type muscle. Secondly, we show that the hypertrophic
      muscle fails to show the normal increase in muscle connective tissue content
      during ageing. Therefore, genetic deletion of myostatin results in an increase in
      contractile elements but a decrease in connective tissue content. We propose a
      model based on the contractile profile of muscle fibres that reconciles this
      apparent incompatible tissue composition phenotype.

PMID- 22463482
TI  - Assessment of the genotoxic potential of Hoechst 33342, SYBR-14 and PI using the
      SOS ChromoTest(TM).
AB  - Fluorochromes in combination with flow cytometry can be used for laboratory
      assessment of semen quality in humans and domestic animals. Some studies have
      reported the potential toxicity of these fluorochromes toward the cells analyzed,
      but not toward the laboratory technician who operates the analytical instrument.
      We tested the genotoxic potential of three fluorochromes, SYBR-14, propidium
      iodide, and Hoechst 33342, using the colorimetric SOS ChromoTest(TM). The test
      revealed no genotoxic potential for any of the three fluorochromes within the
      dilution ranges investigated. We conclude that occasional direct contact with
      these fluorescent probes does not necessarily pose a genotoxic hazard.

PMID- 22463483
TI  - Thermodynamic and energy efficiency analysis of power generation from natural
      salinity gradients by pressure retarded osmosis.
AB  - The Gibbs free energy of mixing dissipated when fresh river water flows into the
      sea can be harnessed for sustainable power generation. Pressure retarded osmosis
      (PRO) is one of the methods proposed to generate power from natural salinity
      gradients. In this study, we carry out a thermodynamic and energy efficiency
      analysis of PRO work extraction. First, we present a reversible thermodynamic
      model for PRO and verify that the theoretical maximum extractable work in a
      reversible PRO process is identical to the Gibbs free energy of mixing. Work
      extraction in an irreversible constant-pressure PRO process is then examined. We
      derive an expression for the maximum extractable work in a constant-pressure PRO
      process and show that it is less than the ideal work (i.e., Gibbs free energy of
      mixing) due to inefficiencies intrinsic to the process. These inherent
      inefficiencies are attributed to (i) frictional losses required to overcome
      hydraulic resistance and drive water permeation and (ii) unutilized energy due to
      the discontinuation of water permeation when the osmotic pressure difference
      becomes equal to the applied hydraulic pressure. The highest extractable work in
      constant-pressure PRO with a seawater draw solution and river water feed solution
      is 0.75 kWh/m(3) while the free energy of mixing is 0.81 kWh/m(3)-a thermodynamic
      extraction efficiency of 91.1%. Our analysis further reveals that the operational
      objective to achieve high power density in a practical PRO process is
      inconsistent with the goal of maximum energy extraction. This study demonstrates
      thermodynamic and energetic approaches for PRO and offers insights on actual
      energy accessible for utilization in PRO power generation through salinity
      gradients.

PMID- 22463485
TI  - Intestinal ellagitannin metabolites ameliorate cytokine-induced inflammation and
      associated molecular markers in human colon fibroblasts.
AB  - Pomegranate ellagitannins (ETs) are transformed in the gut to ellagic acid (EA)
      and its microbiota metabolites, urolithin A (Uro-A) and urolithin B (Uro-B).
      These compounds exert anti-inflammatory effects in vitro and in vivo. The aim of
      this study was to investigate the effects of Uro-A, Uro-B, and EA on colon
      fibroblasts, cells that play a key role in intestinal inflammation. CCD18-Co
      colon fibroblasts were exposed to a mixture of Uro-A, Uro-B, and EA, at
      concentrations comparable to those found in the colon (40 MUM Uro-A, 5 MUM Uro-B,
      1 MUM EA), both in the presence or in the absence of IL-1beta (1 ng/mL) or TNF
      alpha (50 ng/mL), and the effects on fibroblast migration and monocyte adhesion
      were determined. The levels of several growth factors and adhesion cytokines were
      also measured. The mixture of metabolites significantly inhibited colon
      fibroblast migration (~70%) and monocyte adhesion to fibroblasts (~50%). These
      effects were concomitant with a significant down-regulation of the levels of
      PGE(2), PAI-1, and IL-8, as well as other key regulators of cell migration and
      adhesion. Of the three metabolites tested, Uro-A exhibited the most significant
      anti-inflammatory effects. The results show that a combination of the ET
      metabolites found in colon, urolithins and EA, at concentrations achievable in
      the intestine after the consumption of pomegranate, was able to moderately
      improve the inflammatory response of colon fibroblasts and suggest that
      consumption of ET-containing foods has potential beneficial effects on gut
      inflammatory diseases.

PMID- 22463484
TI  - The burden of antenatal heart disease in South Africa: a systematic review.
AB  - BACKGROUND: Maternal mortality in South Africa is rising, and heart conditions
      currently account for 41 per cent of indirect causes of deaths. Little is known
      about the burden of heart disease in pregnant South Africans. METHODS: We
      systematically reviewed the contemporary epidemiology and peripartum outcomes of
      heart disease in South African women attending antenatal care. Searches were
      performed in PubMed, ISI Web of Science, the EBSCO Africa-Wide database, the
      South African Union Catalogue, and the Current and Completed Research database
      (South Africa). References of included articles were also hand-searched. Studies
      reporting epidemiologic data on antenatal heart disease in South Africa were
      included. Data on morbidity and mortality were also collected. RESULTS: Seven
      studies were included in the systematic review. The prevalence of heart disease
      ranged from 123 to 943 per 100,000 deliveries, with a median prevalence of 616
      per 100,000. Rheumatic valvular lesions were the commonest abnormalities,
      although cardiomyopathies were disproportionately high in comparison with other
      developing countries. Peripartum case-fatality rates were as high as 9.5 per cent
      in areas with limited access to care. The most frequent complications were
      pulmonary oedema, thromboembolism, and major bleeding with warfarin use.
      Perinatal mortality ranged from 8.9 to 23.8 per cent, whilst mitral lesions were
      associated with low birth weight. Meta-analysis could not be performed due to
      clinical and statistical heterogeneity of the included studies. CONCLUSION:
      Approximately 0.6 per cent of pregnant South Africans have pre-existing cardiac
      abnormalities, with rheumatic lesions being the commonest. Maternal and perinatal
      morbidity and mortality continue to be very high. We conclude this review by
      summarising limitations of the current literature and recommending standard
      reporting criteria for future reports.

PMID- 22463486
TI  - Treatment of the elderly patient with diffuse large B cell lymphoma.
AB  - The majority of patients with diffuse large B-cell lymphoma are over the age of
      60 years and the management of these patients is often sub-optimal. Intensive
      therapy with curative intent should be given to all patients who can tolerate
      such therapy, and this requires very careful evaluation of each patient prior to
      treatment allocation. A detailed history and examination are required, with
      attention to concomitant disease and existing drug therapy. A quantitative
      assessment of comorbidity and a comprehensive geriatric assessment (CGA) are
      valuable adjuncts to physician judgment. For most elderly patients, the R-CHOP
      regimen (rituximab, cyclophosphamide doxorubicin, vincristine, prednisolone)
      remains the standard of care. Granulocyte colony-stimulating factor should be
      given routinely. Reassessment before each cycle of therapy is essential and
      interim echocardiography should be performed. In patients with cardiac
      insufficiency there are a number of alternative regimens but no definitive 'best
      regimen.' In those patients not treated with curative intent a multi-disciplinary
      approach is essential.

PMID- 22463487
TI  - Covalently assembled NIR nanoplatform for simultaneous fluorescence imaging and
      photodynamic therapy of cancer cells.
AB  - A highly efficient multifunctional nanoplatform for simultaneous upconversion
      luminescence (UCL) imaging and photodynamic therapy has been developed on the
      basis of selective energy transfer from multicolor luminescent
      NaYF(4):Yb(3+),Er(3+) upconversion nanoparticles (UCNPs) to photosensitizers
      (PS). Different from popular approaches based on electrostatic or hydrophobic
      interactions, over 100 photosensitizing molecules were covalently bonded to every
      20 nm UCNP, which significantly strengthened the UCNP-PS linkage and reduced the
      probability of leakage/desorption of the PS. Over 80% UCL was transferred to PS,
      and the singlet oxygen production was readily detected by its feature emission at
      1270 nm. Tests performed on JAR choriocarcinoma and NIH 3T3 fibroblast cells
      verified the efficient endocytosis and photodynamic effect of the nanoplatform
      with 980 nm irradiation specific to JAR cancer cells. Our work highlights the
      promise of using UCNPs for potential image-guided cancer photodynamic therapy.

PMID- 22463488
TI  - The effect of household heads training on long-lasting insecticide-treated bed
      nets utilization: a cluster randomized controlled trial in Ethiopia.
AB  - BACKGROUND: Long-lasting insecticide-treated bed nets (LLITN) have demonstrated
      significant impact in reducing malaria-related childhood morbidity and mortality.
      However, utilization of LLITN by under-five children is not satisfactory in many
      sub-Saharan African countries due to behavioural barriers. Previous studies had
      focused on the coverage and ownership of LLITN. The effect of skill-based
      training for household heads on LLITN utilization had not yet been investigated.
      A cluster-randomized trial on the effect of training of household heads on the
      use of LLITN was done in Ethiopia to fill this knowledge gap. METHODS: The study
      included 22 (11 intervention and 11 control) villages in southwest Ethiopia. The
      intervention consisted of tailored training of household heads about the proper
      use of LLITN and community network system. All households in each group received
      free LLITN. Data were collected at baseline, six and 12 months of the follow up
      periods. Utilization of LLITN in the control and intervention villages was
      compared at baseline and follow up periods. RESULTS: A total of 21,673; 14,735
      and 13,758 individuals were included at baseline, sixth and twelfth months of the
      project period. At the baseline survey, 47.9% of individuals in the intervention
      villages and 68.4% in the control villages reported that they had utilized LLITN
      the night before the survey. At the six month, 81.0% of individuals in the
      intervention villages and 79.3% in the control villages had utilized LLITN. The
      utilization of LLITN in all age groups in the intervention villages was increased
      by 17.7 percentage point (95% CI 9.7-25.6) at sixth month and by 31.0 percentage
      point (95% CI 16.9-45.1) at the twelfth month. Among under-five children, the
      LLITN utilization increased by 31.6 percentage point (95% CI 17.3-45.8) at the
      sixth month and 38.4 percentage point (95% CI 12.1-64.7) at the twelfth months of
      the project period. CONCLUSION: Household level skill-based training has
      demonstrated a marked positive effect in the utilization of LLITN. The effect of
      the intervention steadily increased overtime. Therefore, distribution of LLITN
      should be accompanied by a skill-based training of household heads to improve its
      utilization. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      (ACTR number: ACTRN12610000035022).

PMID- 22463489
TI  - Ti-catalyzed homolytic opening of ozonides: a sustainable C-C bond-forming
      reaction.
AB  - The unprecedented homolytic opening of ozonides promoted and catalyzed by
      titanocene(III) is reported. This novel reaction proceeds at room temperature
      under neutral, mild conditions compatible with many functional groups and
      provides carbon radicals suitable to form C-C bonds via both homocoupling and
      cross-coupling processes. The procedure has been advantageously exploited for the
      straightforward synthesis of the natural product brittonin A.

PMID- 22463490
TI  - Using MRI to measure aerosol deposition.
AB  - This article provides a concise review of the use of magnetic resonance imaging
      (MRI) for measurement of regional aerosol deposition in the lungs. Basic aspects
      of MRI and its use in lung imaging and measurement of regional ventilation are
      introduced. Imaging of hydrogen protons (water) and inhaled hyperpolarized gases
      as the MRI source signals are discussed. The addition of contrast agents to
      aerosol particles in order to allow measurement of regional aerosol deposition is
      considered. Existing in vitro human and in vivo animal model measurements of
      regional aerosol deposition in the respiratory tract demonstrate the capability
      of MRI in this regard. However, as a tool for human deposition studies, current
      approaches require contrast agent doses that are too high to be considered
      competitive with traditional radionuclide aerosol deposition measurement methods.
      Thus, future use of MRI in human studies of regional aerosol deposition is
      predicated on improvement over present approaches.

PMID- 22463491
TI  - Notch1 activation promotes renal cell carcinoma growth via PI3K/Akt signaling.
AB  - Both the Notch1 and PI3K/Akt pathways are aberrantly activated in clear cell
      renal cell carcinoma (CCRCC) and involved in the tumorigenesis. The aim of this
      study was to test our hypothesis that elevated Notch1 signaling activity exerts
      its growth-promoting effects via the PI3K/Akt pathway in CCRCC. To investigate
      the relationship between the two pathways, we enhanced and suppressed the Notch1
      activity respectively in a CCRCC cell line through diverse means, and then
      evaluated ensuing phosphorylated Akt (pAkt) levels. To further study their
      collaboration in promoting tumor growth, cell proliferation assay, colony
      formation assay and cell cycle analysis were conducted under several different
      conditions. Immunostaining of the tissue microarrays was used to determine
      whether the phenomena we observed also existed in vivo. The results showed that
      Notch1 signaling was activated in CCRCC tissue samples and cell lines. Notch1
      activation increased CCRCC cell proliferation, enhanced anchorage-independent
      growth, and accelerated G1/S cell cycle progression. Such effects of the Notch1
      signaling were, at least in part, mediated by the PI3K/Akt pathway. Correlations
      between Notch1, pAkt and Ki-67 protein levels in tissue microarrays reinforced
      our in vitro findings. Taken together, the current study established a functional
      link between the Notch1 and PI3K/Akt pathways in CCRCC.

PMID- 22463492
TI  - Progressive lacunar stroke: review of mechanisms, prognostic features, and
      putative treatments.
AB  - Lacunar stroke is generally considered to have a fair outcome. However 20-30% of
      patients with lacunar stroke worsen neurologically in hours or days after onset,
      reaching eventually an unexpectedly severe disability status. In the field of
      acute stroke, progressive lacunar stroke remains an important unresolved practice
      problem, because as yet no treatment does exist proven to prevent or halt
      progression. Pathophysiology of progression is yet incompletely understood.
      Hemodynamic factors, extension of thrombosis, excitotoxicity, and inflammation,
      have been proposed as possible mechanisms of progression. A few clinical studies
      also aimed at establishing presentation features that may help identifying
      patients at risk of deterioration. In this paper, we review hypothesized
      mechanisms of lacunar stroke progression and possible markers of early
      deterioration. Moreover, based on putative mechanisms and suggestions from
      reported evidence, we propose a few treatments that seem worthy to be tested by
      randomized clinical trials.

PMID- 22463493
TI  - Internight sleep variability: its clinical significance and responsiveness to
      treatment in primary and comorbid insomnia.
AB  - Although sleep diary and actigraphy data are usually collected daily for 1 or 2
      weeks, traditional analytical approaches aggregate these data into mean values.
      Internight variability of sleep often accompanies insomnia. However, few studies
      have explored the relevance of this 'construct' in the context of diagnosis,
      clinical impact, treatment effects and/or whether having 'variable sleep' carries
      any prognostic significance. We explored these questions by conducting secondary
      analyses of data from a randomized clinical trial. The sample included primary
      (PI: n = 40) and comorbid insomnia (CMI: n = 41) sufferers receiving four
      biweekly sessions of cognitive-behavioural therapy (CBT) or sleep hygiene
      education. Using the within-subject standard deviations of diary- and actigraphy
      derived measures collected for 2-week periods [sleep onset latency (SOL), wake
      after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE)], we
      found that CMI sufferers displayed more variable self-reported SOLs and SEs than
      PI sufferers. However, higher variability in diary and actigraphy-derived
      measures was related to poorer sleep quality only within the PI group, as
      measured by the Pittsburgh Sleep Quality Index (PSQI). Within both groups, the
      variability of diary-derived measures was reduced after CBT, but the variability
      of actigraphy-derived measures remained unchanged. Interestingly, the variability
      of actigraphy measures at baseline was correlated with PSQI scores at 6-month
      follow-up. Higher SOL variability was associated with worse treatment outcomes
      within the PI group, whereas higher WASO variability was correlated with better
      treatment outcomes within the CMI group. Sleep variability differences across
      insomnia diagnoses, along with their distinctive correlates, suggest that
      mechanisms underlying the sleep disruption/complaint and treatment response in
      both patient groups are distinct. Further studies are warranted to support
      variability as a useful metric in insomnia studies.

PMID- 22463494
TI  - Desulfonylative radical ring closure onto aromatics. A modular route to
      benzazepin-2-ones and 5-arylpiperidin-2-ones.
AB  - Adducts from the intermolecular radical addition of N-xanthylacetyl-N
      methanesulfanilides to Boc-protected allylamine undergo ring closure with loss of
      a methanesulfonyl radical to give benzazepin-2-ones. Upon deprotection and
      exposure to triethylamine, these compounds rearrange into 5-aryl-2-piperidones.
      This approach also represents a useful route to benzazepin-2-ones unsubstituted
      on the nitrogen atom of the azepinone ring.

PMID- 22463495
TI  - Structures promoting research, training, and technology transfer in mobility:
      lessons learned from a visit to European centers.
AB  - The purpose of this paper is to describe the education, research, technology
      transfer, and cooperative models that appear to have the greatest likelihood of
      successfully tackling the issue of technology to improve mobility. Ideally better
      models in each of these areas will lead to an increased number of researchers who
      are more productive. There will be increased international collaboration that
      will allow for better research with small and/or disadvantaged populations, and
      the research completed will lead to changes in clinical care that positively
      impact individuals with impair mobility.

PMID- 22463496
TI  - Sleep disturbances in Parkinson's disease with emphasis on rapid eye movement
      sleep behavior disorder.
AB  - Sleep disturbances are common in patients with Parkinson's disease (PD). These
      disturbances can primarily affect the patient's quality of life and may worsen
      the symptoms of PD. Among the multiple sleep disturbances in PD patients, there
      has been a marked growing interest in rapid eye movement (REM) sleep behavior
      disorder (RBD). This is likely due to the fact that RBD has been proven to
      precede the motor symptoms of PD by many years. The aim of this article is to
      examine the sleep disturbances found in PD, with special attention to RBD as a
      premotor symptom of PD, as well as to assess its proposed related
      pathophysiology. MEDLINE (1966-March 2010), American Academy of Sleep Medicine's,
      The International Classification of Sleep Disorders, and current textbooks of
      sleep medicine were searched for relevant information. Search terms: RBD, sleep
      disturbances, Parkinson's disease, and pre-motor were used. Excessive daytime
      sleepiness (EDS), sleep attack, insomnia, restless leg syndrome (RLS), sleep
      disordered breathing (SDB), and RBD are sleep disturbances commonly found in the
      literature related to PD. Sleep benefit has been proven to lessen PD motor
      symptoms. RBD has been described as a premotor symptom of PD in several
      prospective, retrospective, and cross-sectional studies. Sleep disturbances in PD
      can result secondarily to natural disease progression, as a side effect of the
      medications used in PD, or in result of pre-clinical pathology. Treatment of
      sleep disturbances in PD patients is crucial, as what is termed as, "sleep
      benefit effect" has been shown to improve the symptoms of PD.

PMID- 22463497
TI  - Effect of intake of linoleic acid and alpha-linolenic acid levels on conversion
      into long-chain polyunsaturated fatty acids in backfat and in intramuscular fat
      of growing pigs.
AB  - A study was conducted to determine the effect of two levels of linoleic acid (LA)
      intake at either high or low alpha-linolenic acid (ALA) intake on their
      conversion and subsequent deposition into long-chain (20-22 C-atoms)
      polyunsaturated fatty acids (LC PUFA) in muscle and backfat in growing pigs. In a
      2 * 2 factorial arrangement, 32 gilts from 8 litters were assigned to one of four
      dietary treatments, varying in LA and ALA intakes. Low ALA and LA intakes were
      0.15 and 1.31 g/(kg BW(0.75) /day), respectively, and high ALA and LA intakes
      were 1.48 and 2.65 g/(kg BW(0.75) /day) respectively. There was a close positive
      relation between intake of ALA and the concentration of ALA in backfat and in
      intramuscular fat. Dietary ALA did not affect the concentration of
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), but increased
      docosapentaenoic acid (DPA) in backfat. High ALA intake did not significantly
      affect DHA but significantly increased EPA, 20:3 n-3 and DPA concentrations in
      intramuscular fat. The n-3 LC PUFA proportion in backfat was increased from
      approximately 1-3%, which may be useful to enrich meat with these fatty acids.
      The effect of ALA intake on n-3 LC PUFA was suppressed by LA intake. Dietary ALA
      suppressed the concentration of n-6 LC PUFA in blood plasma by more than 50%.
      When compared at equal incremental dose, the inhibiting effect of ALA on blood
      arachidonic acid was stronger than the stimulating effect of LA as precursor.

PMID- 22463498
TI  - Transition Metal d Complexes. II. Reactions of d-Cycloheptatrienylmolybdenum
      Dicarbonyl Iodide with Chelating Group Va Ligands.

PMID- 22463499
TI  - Psychotherapeutic approaches to non-suicidal self-injury in adolescents.
AB  - Non-suicidal self-injury (NSSI) among adolescents is gaining increasing
      attention in both clinical and scientific arenas. The lifetime prevalence of NSSI
      is estimated to vary between 7.5% to 8% for preadolescents, increasing to between
      12% and 23% for adolescents. Despite the prevalence and the increasing interest
      in NSSI, few psychotherapeutic treatments have been designed specifically for
      NSSI, and no treatments have been evaluated specifically for the treatment of
      NSSI among adolescents. Consequently, child and adolescent clinicians are left
      with little evidence-based guidance for treating this challenging population. To
      provide some guidance, evaluations of treatments for adults with NSSI and for
      adolescents with related conditions, such as deliberate self-harm and borderline
      personality disorder, are reviewed. Clinical guidelines and resources are also
      discussed to assist with the gaps in the knowledge base for treatment of NSSI
      among adolescents.

PMID- 22463500
TI  - Association between psychological distress and a sense of contribution to society
      in the workplace.
AB  - BACKGROUND: Globally, mental health promotion related to psychological distress
      in the workplace has become a great concern, and a focus of much research
      attention. However, a sense of contribution to society and sense of bonding with
      the workplace have not been examined in relation to psychological distress. Thus,
      the purpose of this study is to examine whether these two factors are associated
      with psychological distress. METHODS: We conducted a cross-sectional survey of
      1137 full-time employees who worked in systems engineering, sales, or
      administration at a Japanese company. Participant's sense of contribution to
      society, sense of bonding with the workplace, psychological distress, and
      qualitative job stress (quantitative and qualitative workloads, job-control
      latitude, and support from supervisors, co-workers and family) were assessed with
      a questionnaire. We performed multiple logistic regression analyses to examine
      associations between psychological distress and sense of contribution to society
      and of bonding with the workplace. RESULTS: A high sense of contribution to
      society was significantly associated with a high sense of bonding with the
      workplace (Spearman's rho = 0.47, p < 0.01). A sense of contribution to society
      was negatively associated with psychological distress after adjusting for job
      stress factors (OR = 2.05, 95% CI 0.99-4.23) or sociodemographic characteristics
      of participants (OR = 2.92, 1.53-5.59). After adjusting for job stress factors as
      well as sociodemographic characteristics, the association became weaker. A sense
      of bonding with the workplace was negatively associated with psychological
      distress after adjusting for sociodemographic characteristics (OR = 2.49, 1.29
      4.79). However, this association was not observed after adjusting for job stress
      factors. CONCLUSIONS: Psychological distress in the workplace was associated with
      sense of contribution to society. Therefore, workplace mental health promotion
      should consider the workers' sense of contribution to society.

PMID- 22463501
TI  - Density and spin response of a strongly interacting Fermi gas in the attractive
      and quasirepulsive regime.
AB  - Recent experimental advances in ultracold Fermi gases allow for exploring
      response functions under different dynamical conditions. In particular, the issue
      of obtaining a "quasirepulsive" regime starting from a Fermi gas with an
      attractive interparticle interaction while avoiding the formation of the two-body
      bound state is currently debated. Here, we provide a calculation of the density
      and spin response for a wide range of temperature and coupling both in the
      attractive and quasirepulsive regime, whereby the system is assumed to evolve
      nonadiabatically toward the "upper branch" of the Fermi gas. A comparison is made
      with the available experimental data for these two quantities.

PMID- 22463502
TI  - Thermalization in nature and on a quantum computer.
AB  - In this work, we show how Gibbs or thermal states appear dynamically in closed
      quantum many-body systems, building on the program of dynamical typicality. We
      introduce a novel perturbation theorem for physically relevant weak system-bath
      couplings that is applicable even in the thermodynamic limit. We identify
      conditions under which thermalization happens and discuss the underlying physics.
      Based on these results, we also present a fully general quantum algorithm for
      preparing Gibbs states on a quantum computer with a certified runtime and error
      bound. This complements quantum Metropolis algorithms, which are expected to be
      efficient but have no known runtime estimates and only work for local
      Hamiltonians.

PMID- 22463503
TI  - Feasible optical weak measurements of complementary observables via a single
      Hamiltonian.
AB  - A general formalism for joint weak measurements of a pair of complementary
      observables is given. The standard process of optical three-wave mixing in a
      nonlinear crystal (such as in parametric down-conversion) is suitable for such
      tasks. To obtain the weak value of a variable A one performs weak measurements
      twice, with different initial states of the meter field. This seems to be a
      drawback, but as a compensation we get for free the weak value of a complementary
      variable B. The scheme is tunable and versatile: one has access to a continuous
      set of possible weak measurements of a pair of observables. The scheme increases
      signal-to-noise ratio with respect to the case without postselection.

PMID- 22463504
TI  - Geometric phase contribution to quantum nonequilibrium many-body dynamics.
AB  - We study the influence of geometry of quantum systems underlying space of states
      on its quantum many-body dynamics. We observe an interplay between dynamical and
      topological ingredients of quantum nonequilibrium dynamics revealed by the
      geometrical structure of the quantum space of states. As a primary example we use
      the anisotropic XY ring in a transverse magnetic field with an additional time
      dependent flux. In particular, if the flux insertion is slow, nonadiabatic
      transitions in the dynamics are dominated by the dynamical phase. In the opposite
      limit geometric phase strongly affects transition probabilities. This interplay
      can lead to a nonequilibrium phase transition between these two regimes. We also
      analyze the effect of geometric phase on defect generation during crossing a
      quantum-critical point.

PMID- 22463505
TI  - Long-lived dipolar molecules and Feshbach molecules in a 3D optical lattice.
AB  - We have realized long-lived ground-state polar molecules in a 3D optical lattice,
      with a lifetime of up to 25 s, which is limited only by off-resonant scattering
      of the trapping light. Starting from a 2D optical lattice, we observe that the
      lifetime increases dramatically as a small lattice potential is added along the
      tube-shaped lattice traps. The 3D optical lattice also dramatically increases the
      lifetime for weakly bound Feshbach molecules. For a pure gas of Feshbach
      molecules, we observe a lifetime of greater than 20 s in a 3D optical lattice;
      this represents a 100-fold improvement over previous results. This lifetime is
      also limited by off-resonant scattering, the rate of which is related to the size
      of the Feshbach molecule. Individually trapped Feshbach molecules in the 3D
      lattice can be converted to pairs of K and Rb atoms and back with nearly 100%
      efficiency.

PMID- 22463506
TI  - Tuning the tricritical point with spin-orbit coupling in polarized fermionic
      condensates.
AB  - We investigate a two-component atomic Fermi gas with population imbalance in the
      presence of Rashba-type spin-orbit coupling (SOC). As a competition between SOC
      and population imbalance, the finite-temperature phase diagram reveals a large
      variety of new features, including the expanding of the superfluid state regime
      and the shrinking of both the phase separation and the normal regimes. For
      sufficiently strong SOC, the phase separation region disappears, giving way to
      the superfluid state. We find that the tricritical point moves toward a regime of
      low temperature, high magnetic field, and high polarization as the SOC increases.

PMID- 22463507
TI  - Zeno effect for quantum computation and control.
AB  - It is well known that the quantum Zeno effect can protect specific quantum states
      from decoherence by using projective measurements. Here we combine the theory of
      weak measurements with stabilizer quantum error correction and detection codes.
      We derive rigorous performance bounds which demonstrate that the Zeno effect can
      be used to protect appropriately encoded arbitrary states to arbitrary accuracy
      while at the same time allowing for universal quantum computation or quantum
      control.

PMID- 22463508
TI  - Quantum system identification.
AB  - The aim of quantum system identification is to estimate the ingredients inside a
      black box, in which some quantum-mechanical unitary process takes place, by just
      looking at its input-output behavior. Here we establish a basic and general
      framework for quantum system identification, that allows us to classify how much
      knowledge about the quantum system is attainable, in principle, from a given
      experimental setup. We show that controllable closed quantum systems can be
      estimated up to unitary conjugation. Prior knowledge on some elements of the
      black box helps the system identification. We present an example in which a Bell
      measurement is more efficient to identify the system. When the topology of the
      system is known, the framework enables us to establish a general criterion for
      the estimability of the coupling constants in its Hamiltonian.

PMID- 22463509
TI  - Density of States for a specified correlation function and the energy landscape.
AB  - The degeneracy of two-phase disordered microstructures consistent with a
      specified correlation function is analyzed by mapping it to a ground-state
      degeneracy. We determine for the first time the associated density of states via
      a Monte Carlo algorithm. Our results are explained in terms of the roughness of
      an energy landscape, defined on a hypercubic configuration space. The use of a
      Hamming distance in this space enables us to define a roughness metric, which is
      calculated from the correlation function alone and related quantitatively to the
      structural degeneracy. This relation is validated for a wide variety of
      disordered structures.

PMID- 22463510
TI  - Test of the gravitational inverse square law at millimeter ranges.
AB  - We report a new test of the gravitational inverse square law at millimeter ranges
      by using a dual-modulation torsion pendulum. An I-shaped symmetric pendulum and I
      shaped symmetric attractors were adopted to realize a null experimental design.
      The non-Newtonian force between two macroscopic tungsten plates is measured at
      separations ranging down to 0.4 mm, and the validity of the null experimental
      design was checked by non-null Newtonian gravity measurements. We find no
      deviations from the Newtonian inverse square law with 95% confidence level, and
      this work establishes the most stringent constraints on non-Newtonian interaction
      in the ranges from 0.7 to 5.0 mm, and a factor of 8 improvement is achieved at
      the length scale of several millimeters.

PMID- 22463511
TI  - Connecting neutron star observations to three-body forces in neutron matter and
      to the nuclear symmetry energy.
AB  - Using a phenomenological form of the equation of state of neutron matter near the
      saturation density which has been previously demonstrated to be a good
      characterization of quantum Monte Carlo simulations, we show that currently
      available neutron star mass and radius measurements provide a significant
      constraint on the equation of state of neutron matter. At higher densities we
      model the equation of state by using polytropes and a quark matter model. We show
      that observations offer an important constraint on the strength of the three-body
      force in neutron matter, and thus some theoretical models of the three-body force
      may be ruled out by currently available astrophysical data. In addition, we
      obtain an estimate of the symmetry energy of nuclear matter and its slope that
      can be directly compared to the experiment and other theoretical calculations.

PMID- 22463512
TI  - Black holes in scalar-tensor gravity.
AB  - Hawking has proven that black holes which are stationary as the end point of
      gravitational collapse in Brans-Dicke theory (without a potential) are no
      different than in general relativity. We extend this proof to the much more
      general class of scalar-tensor and f(R) gravity theories, without assuming any
      symmetries apart from stationarity.

PMID- 22463513
TI  - Proton-helium spectral anomaly as a signature of cosmic ray accelerator.
AB  - The much-anticipated proof of cosmic ray (CR) acceleration in supernova remnants
      must hinge on the full consistency of acceleration theory with the observations;
      direct proof is impossible because of CR-orbit scrambling. Recent observations
      indicate deviations between helium and proton CR rigidity spectra inconsistent
      with the theory. By considering an initial (injection) phase of the diffusive
      shock acceleration, where elemental similarity does not apply, we demonstrate
      that the spectral difference is, in fact, a unique signature of the acceleration
      mechanism. Collisionless shocks inject more He(2+) when they are stronger and so
      produce harder He(2+) spectra. The injection bias is due to Alfven waves driven
      by the more abundant protons, so the He(2+) ions are harder to trap by these
      waves. By fitting the p/He ratio to the PAMELA data, we bolster the diffusive
      shock acceleration case for resolving the century-old mystery of CR origin.

PMID- 22463514
TI  - Integrable spin chain for the SL(2,R)/U(1) black hole sigma model.
AB  - We introduce a spin chain based on finite-dimensional spin-1/2 SU(2)
      representations but with a non-Hermitian "Hamiltonian" and show, using mostly
      analytical techniques, that it is described at low energies by the SL(2,R)/U(1)
      Euclidian black hole conformal field theory. This identification goes beyond the
      appearance of a noncompact spectrum; we are also able to determine the density of
      states, and show that it agrees with the formulas in [J. Maldacena, H. Ooguri,
      and J. Son, J. Math. Phys. (N.Y.) 42, 2961 (2001)] and [A. Hanany, N. Prezas, and
      J. Troost, J. High Energy Phys. 04 (2002) 014], hence providing a direct
      "physical measurement" of the associated reflection amplitude.

PMID- 22463515
TI  - Phenomenology of TeV little string theory from holography.
AB  - We study the graviton phenomenology of TeV little string theory by exploiting its
      holographic gravity dual five-dimensional theory. This dual corresponds to a
      linear dilaton background with a large bulk that constrains the standard model
      fields on the boundary of space. The linear dilaton geometry produces a unique
      Kaluza-Klein graviton spectrum that exhibits a ~TeV mass gap followed by a near
      continuum of narrow resonances that are separated from each other by only ~30
      GeV. Resonant production of these particles at the LHC is the signature of this
      framework that distinguishes it from large extra dimensions, where the Kaluza
      Klein states are almost a continuum with no mass gap, and warped models, where
      the states are separated by a TeV.

PMID- 22463516
TI  - Solution to the flavor problem of warped extra-dimension models.
AB  - A minimal solution to the flavor problem of warped extra-dimension models, i.e.,
      the excessive mixed-chirality contribution to CP violation in K-K - mixing
      arising from Kaluza-Klein (KK) gluon exchange, is proposed. Extending the strong
      interaction gauge group in the bulk by an additional SU(3), and breaking this
      symmetry to QCD via boundary conditions, the constraints arising from the
      epsilon(K) parameter are significantly relaxed. As a result, KK scales M(KK)~2
      TeV are consistent with all flavor observables without significant fine-tuning.
      The model predicts an extended Higgs sector featuring massive color-octet scalars
      and a tower of KK pseudoaxial gluon resonances, whose existence is not in
      conflict with recent LHC dijet bounds.

PMID- 22463518
TI  - Constraint on parity-violating muonic forces.
AB  - Using the nonobservance of missing mass events in the leptonic kaon decay K->MUX,
      we place a strong constraint on exotic parity-violating gauge interactions of the
      right-handed muon. By way of illustration, we apply it to an explanation of the
      proton size anomaly that invokes such a new force; scenarios in which the gauge
      boson decays invisibly or is long lived are constrained.

PMID- 22463519
TI  - Puzzle of anomalously large isospin violations in eta(1405/1475)->3pi.
AB  - The BES-III Collaboration recently reported the observation of anomalously large
      isospin violations in J/psi->gammaeta(1405/1475)->gammapi(0)f(0)(980)->gamma+3pi,
      where the f(0)(980) in the pipi invariant mass spectrum appears to be much
      narrower (~10 MeV) than the peak width (~50 MeV) measured in other processes. We
      show that a mechanism, named as triangle singularity (TS), can produce a narrow
      enhancement between the charged and neutral KK- thresholds, i.e., 2m(K(+/
      ))~2m(K(0)). It can also lead to different invariant mass spectra for
      eta(1405/1475)->a(0)(980)pi and KK -*+c.c., which can possibly explain the long
      standing puzzle about the need for two close states eta(1405) and eta(1475) in
      etapipi and KK-pi, respectively. The TS could be a key to our understanding of
      the nature of eta(1405/1475) and advance our knowledge about the mixing between
      a(0)(980) and f(0)(980).

PMID- 22463520
TI  - Searching for stoponium along with the Higgs boson.
AB  - Stoponium, a bound state of the top squark and its antiparticle in a
      supersymmetric model, may be found in the ongoing Higgs searches at the LHC. Its
      WW and ZZ detection ratios relative to the standard model Higgs boson can be more
      than unity from the WW* threshold to the two Higgs threshold. The gammagamma
      channel is equally promising. Some regions of the stoponium mass below 150 GeV
      are already being probed by the ATLAS and CMS experiments.

PMID- 22463521
TI  - Neutrino cosmology after WMAP 7-year data and LHC first Z' bounds.
AB  - The gauge-extended U(1)(C)*SU(2)(L)*U(1)(I(R))*U(1)(L) model elevates the global
      symmetries of the standard model (baryon number B and lepton number L) to local
      gauge symmetries. The U(1)(L) symmetry leads to three superweakly interacting
      right-handed neutrinos. This also renders a B-L symmetry nonanomalous. The
      superweak interactions of these Dirac states permit nu(R) decoupling just above
      the QCD phase transition: 175 is < or approximately equal to T(nu(R))(dec)/MeV is
      < or approximately equal to 250. In this transitional region, the residual
      temperature ratio between nu(L) and nu(R) generates extra relativistic degrees of
      freedom at BBN and at the CMB epochs. Consistency with both WMAP 7-year data and
      recent estimates of the primordial 4He mass fraction is achieved for 3<M(B
      L)/TeV<6. The model is fully predictive, and can be confronted with dijet and
      dilepton data from LHC7 and, eventually, LHC14.

PMID- 22463522
TI  - Sneutrino dark matter in gauged inverse seesaw models for neutrinos.
AB  - Extending the minimal supersymmetric standard model to explain small neutrino
      masses via the inverse seesaw mechanism can lead to a new light supersymmetric
      scalar partner which can play the role of inelastic dark matter (IDM). It is a
      linear combination of the superpartners of the neutral fermions in the theory
      (the light left-handed neutrino and two heavy standard model singlet neutrinos)
      which can be very light with mass in ~5-20 GeV range, as suggested by some
      current direct detection experiments. The IDM in this class of models has keV
      scale mass splitting, which is intimately connected to the small Majorana masses
      of neutrinos. We predict the differential scattering rate and annual modulation
      of the IDM signal which can be testable at future germanium- and xenon-based
      detectors.

PMID- 22463525
TI  - Resonant circular dichroism of chiral metal-organic complex.
AB  - A sizable enhancement of the circular dichroism in photoelectron spectroscopy has
      been measured and computed for the metal complex Delta-cobalt(III) tris
      acetylacetonate highest occupied molecular orbital state in the region of the Co
      3p->3d Fano resonance. In the resonance the dichroism reaches the maximum value
      of 5% and even changes its sign as compared to the direct photoionization
      channel. We ascribe this enhancement to electron correlation processes, namely,
      with the coupling between discrete excitations and the continuum, which is
      correctly described in the time dependent density functional theory (TDDFT)
      framework. These findings open new physical aspects of photoelectron circular
      dichroism that now can be interpreted not only via the simple direct ionization,
      but also through more complex electron correlation processes.

PMID- 22463526
TI  - Exact wave functions of two-electron quantum rings.
AB  - We demonstrate that the Schrodinger equation for two electrons on a ring, which
      is the usual paradigm to model quantum rings, is solvable in closed form for
      particular values of the radius. We show that both polynomial and irrational
      solutions can be found for any value of the angular momentum and that the singlet
      and triplet manifolds, which are degenerate, have distinct geometric phases. We
      also study the nodal structure associated with these two-electron states.

PMID- 22463527
TI  - Effect of internal energy on the repulsive Coulomb barrier of polyanions.
AB  - The nature of the repulsive Coulomb barrier in isolated molecular polyanions is
      studied by means of the photodetachment dynamics of the S(1) excited state of the
      fluorescein dianion which is bound solely by the repulsive Coulomb barrier.
      Photoelectron spectra reveal a feature at a constant electron kinetic energy,
      regardless of the excitation energy. This is explained by using an adiabatic
      tunneling picture for electron loss through successive repulsive Coulomb barriers
      correlating to vibrationally excited states. This physical picture is supported
      by time-resolved photoelectron spectra, showing that the tunneling lifetime is
      also invariant with excitation energy.

PMID- 22463528
TI  - Generation and characterization of multimode quantum frequency combs.
AB  - Multimode nonclassical states of light are an essential resource in quantum
      computation with continuous variables, for example, in cluster state computation.
      We report in this Letter the first experimental evidence of a multimode
      nonclassical frequency comb in a femtosecond synchronously pumped optical
      parametric oscillator. In addition to a global reduction of its quantum intensity
      fluctuations, the system features quantum correlations between different parts of
      its frequency spectrum. This allows us to show that the frequency comb is
      composed of several uncorrelated eigenmodes having specific spectral shapes, two
      of them at least being squeezed, and to characterize their spectral shapes.

PMID- 22463529
TI  - Conditional detection of pure quantum states of light after storage in a Tm-doped
      waveguide.
AB  - We demonstrate the conditional detection of time-bin qubits after storage in and
      retrieval from a photon-echo-based waveguide quantum memory. Each qubit is
      encoded into one member of a photon pair produced via spontaneous parametric down
      conversion, and the conditioning is achieved by the detection of the other member
      of the pair. By performing projection measurements with the stored and retrieved
      photons onto different bases, we obtain an average storage fidelity of 0.885+/
      0.020, which exceeds the relevant classical bounds and shows the suitability of
      our integrated light-matter interface for future applications of quantum
      information processing.

PMID- 22463517
TI  - Observation of exclusive gammagamma production in pp- collisions at ?s=1.96 TeV.
AB  - We have observed exclusive gammagamma production in proton-antiproton collisions
      at ?s=1.96 TeV, using data from 1.11+/-0.07 fb(-1) integrated luminosity taken by
      the Run II Collider Detector at Fermilab. We selected events with two
      electromagnetic showers, each with transverse energy E(T)>2.5 GeV and
      pseudorapidity |eta|<1.0, with no other particles detected in -7.4<eta<+7.4. The
      two showers have similar E(T) and azimuthal angle separation Deltaphi~pi; 34
      events have two charged particle tracks, consistent with the QED process pp-
      >p+e(+)e(-)+p- by two-photon exchange, while 43 events have no charged tracks.
      The number of these events that are exclusive pi(0)pi(0) is consistent with zero
      and is <15 at 95% C.L. The cross section for pp-->p+gammagamma+p- with
      |eta(gamma)|<1.0 and E(T)(gamma)>2.5 GeV is 2.48(-0.35)(+0.40)(stat)(
      0.51)(+0.40)(syst) pb.

PMID- 22463530
TI  - Control of material damping in high-Q membrane microresonators.
AB  - We study the mechanical quality factors of bilayer aluminum-silicon-nitride
      membranes. By coating ultrahigh-Q Si(3)N(4) membranes with a more lossy metal, we
      can precisely measure the effect of material loss on Q's of tensioned resonator
      modes over a large range of frequencies. We develop a theoretical model that
      interprets our results and predicts the damping can be reduced significantly by
      patterning the metal film. Using such patterning, we fabricate Al-Si(3)N(4)
      membranes with ultrahigh Q at room temperature. Our work elucidates the role of
      material loss in the Q of membrane resonators and informs the design of hybrid
      mechanical oscillators for optical-electrical-mechanical quantum interfaces.

PMID- 22463531
TI  - Observation of sub-Bragg diffraction of waves in crystals.
AB  - We investigate the diffraction conditions and associated formation of stop gaps
      for waves in crystals with different Bravais lattices. We identify a prominent
      stop gap in high-symmetry directions that occurs at a frequency below the
      ubiquitous first-order Bragg condition. This sub-Bragg-diffraction condition is
      demonstrated by reflectance spectroscopy on two-dimensional photonic crystals
      with a centered rectangular lattice, revealing prominent diffraction peaks for
      both the sub-Bragg and first-order Bragg conditions. These results have
      implications for wave propagation in 2 of the 5 two-dimensional Bravais lattices
      and 7 out of 14 three-dimensional Bravais lattices, such as centered rectangular,
      triangular, hexagonal, and body-centered cubic.

PMID- 22463532
TI  - From electromagnetically induced transparency to superscattering with a single
      structure: a coupled-mode theory for doubly resonant structures.
AB  - We observe from simulations that a doubly resonant structure can exhibit spectral
      behavior analogous to electromagnetically induced transparency, as well as
      superscattering, depending on the excitation. We develop a coupled-mode theory
      that explains this behavior in terms of the orthogonality of the radiation
      patterns of the eigenmodes. These results provide insight in the general
      electromagnetic properties of photonic nanostructures and metamaterials.

PMID- 22463533
TI  - Generation of localized modes in an electrical lattice using subharmonic driving.
AB  - We show experimentally and numerically that an intrinsic localized mode (ILM) can
      be stably produced (and experimentally observed) via subharmonic, spatially
      homogeneous driving in the context of a nonlinear electrical lattice. The precise
      nonlinear spatial response of the system has been seen to depend on the relative
      location in frequency between the driver frequency, omega(d), and the bottom of
      the linear dispersion curve, omega(0). If omega(d)/2 lies just below omega(0),
      then a single ILM can be generated in a 32-node lattice, whereas, when omega(d)/2
      lies within the dispersion band, a spatially extended waveform resembling a train
      of ILMs results. To our knowledge, and despite its apparently broad relevance,
      such an experimental observation of subharmonically driven ILMs has not been
      previously reported.

PMID- 22463534
TI  - Crossover from hydrodynamics to the kinetic regime in confined nanoflows.
AB  - We present an experimental study of a confined nanoflow, which is generated by a
      sphere oscillating in the proximity of a flat solid wall in a simple fluid.
      Varying the oscillation frequency, the confining length scale, and the fluid mean
      free path over a broad range provides a detailed map of the flow. We use this
      experimental map to construct a scaling function, which describes the nanoflow in
      the entire parameter space, including both the hydrodynamic and the kinetic
      regimes. Our scaling function unifies previous theories based on the slip
      boundary condition and the effective viscosity.

PMID- 22463523
TI  - Measurements of the angular distributions in the decays B->K(*)MU(+)MU(-) at CDF.
AB  - We report an indirect search for nonstandard model physics using the flavor
      changing neutral current decays B->K(*)MU(+)MU(-). We reconstruct the decays and
      measure their angular distributions, as a function of q(2)=M(MUMU)(2)c(2), where
      M(MUMU) is the dimuon mass, in pp- collisions at ?s=1.96 TeV using a data sample
      corresponding to an integrated luminosity of 6.8 fb(-1). The transverse
      polarization asymmetry A(T)(2) and the time-reversal-odd charge-and-parity
      asymmetry A(im) are measured for the first time, together with the K*
      longitudinal polarization fraction F(L) and the muon forward-backward asymmetry
      A(FB) for the decays B(0)->K(*0)MU(+)MU(-) and B(+)->K(*+)MU(+)MU(-). The B
      >K*MU(+)MU(-) forward-backward asymmetry in the most sensitive kinematic regime,
      1<=q(2)<6 GeV(2)/c(2), is measured to be A(FB)=0.29(-0.23)(+0.20)(stat)+/
      0.07(syst), the most precise result to date. No deviations from the standard
      model predictions are observed.

PMID- 22463535
TI  - Broadband cloaking in stratified seas.
AB  - Here we show that floating objects in stratified fluids can be cloaked against
      broadband incident waves by properly architecting the bottom corrugations. The
      presented invisibility cloaking of gravity waves is achieved utilizing a
      nonlinear resonance concept that occurs between surface and internal waves
      mediated by the bottom topography. Our cloak bends wave rays from the surface
      into the body of the fluid. Wave rays then pass underneath the floating object
      and may be recovered back to the free surface at the downstream bearing no trace
      of diffraction or scattering. The cloak is the proper architecture of bottom
      corrugations only, and hence is surface noninvasive. The presented scheme is a
      nonlinear alternative to the transformation-based cloaking, but in the context of
      dispersive waves.

PMID- 22463536
TI  - Nonaxisymmetric anisotropy of solar wind turbulence as a direct test for models
      of magnetohydrodynamic turbulence.
AB  - Single point spacecraft observations of the turbulent solar wind flow exhibit a
      characteristic nonaxisymmetric anisotropy that depends sensitively on the
      perpendicular power spectral exponent. We use this nonaxisymmetric anisotropy as
      a function of wave vector direction to test models of MHD turbulence. Using
      Ulysses magnetic field observations in the fast, quiet polar solar wind we find
      that the Goldreich-Sridhar model of MHD turbulence is not consistent with the
      observed anisotropy, whereas the observations are well reproduced by the
      "slab+2D" model. The Goldreich-Sridhar model alone cannot account for the
      observations unless an additional component is also present.

PMID- 22463537
TI  - Time-resolved measurements of hot-electron equilibration dynamics in high
      intensity laser interactions with thin-foil solid targets.
AB  - Time-resolved K(alpha) spectroscopy has been used to infer the hot-electron
      equilibration dynamics in high-intensity laser interactions with picosecond
      pulses and thin-foil solid targets. The measured K(alpha)-emission pulse width
      increases from ~3 to 6 ps for laser intensities from ~10(18) to 10(19) W/cm(2).
      Collisional energy-transfer model calculations suggest that hot electrons with
      mean energies from ~0.8 to 2 MeV are contained inside the target. The inferred
      mean hot-electron energies are broadly consistent with ponderomotive scaling over
      the relevant intensity range.

PMID- 22463538
TI  - Quantum gray solitons in confining potentials.
AB  - We define and study holelike excitations (the Lieb II mode) in a weakly
      interacting Bose liquid subject to external confinement. These excitations are
      obtained by semiclassical quantization of gray solitons propagating on top of a
      Thomas-Fermi background. Radiation of phonons by an accelerated gray soliton
      leads to a finite lifetime of these excitations. It is shown that, for a large
      number of trapped atoms, most of the Lieb II levels can be experimentally
      resolved.

PMID- 22463539
TI  - Doublon relaxation in the Bose-Hubbard model.
AB  - The decay of a high-energy double occupancy state, doublon, in a narrow-band
      lattice requires the creation of a coherent many-particle excitation. This leads
      to an exponentially long relaxation time of such a state. We show that, if the
      average occupation number is sufficiently small, the corresponding exponent may
      be evaluated exactly. To this end we develop the quasiclassical approach to
      calculation of the high-order tree-level decay amplitudes.

PMID- 22463540
TI  - Isolated quantum heat engine.
AB  - We present a theoretical and numerical analysis of a quantum system that is
      capable of functioning as a heat engine. This system could be realized
      experimentally using cold bosonic atoms confined to a double well potential that
      is created by splitting a harmonic trap with a focused laser. The system shows
      thermalization, and can model a reversible heat engine cycle. This is the first
      demonstration of the operation of a heat engine with a finite quantum heat bath.

PMID- 22463541
TI  - Elastic moduli inheritance and the weakest link in bulk metallic glasses.
AB  - We show that a variety of bulk metallic glasses (BMGs) inherit their Young's
      modulus and shear modulus from the solvent components. This is attributed to
      preferential straining of locally solvent-rich configurations among tightly
      bonded atomic clusters, which constitute the weakest link in an amorphous
      structure. This aspect of inhomogeneous deformation, also revealed by our in situ
      neutron diffraction studies of an elastically deformed BMG, suggests a rubberlike
      viscoelastic behavior due to a hierarchy of atomic bonds in BMGs.

PMID- 22463542
TI  - Quantitative characterization of critical nanoclusters nucleated on large single
      molecules.
AB  - First order phase transitions involve nucleation, formation of nanoscale regions
      of a new phase within a metastable parent phase. Using the heterogeneous
      nucleation theorem we show how clusters formed by nucleation on single molecules
      evolve from the gas phase and determine the critical size beyond which
      condensation starts to form aerosol particles. Our experiments reveal the
      activation of molecules into droplets to happen via formation of critical
      clusters substantially larger than the seed molecule. The nanosized critical
      clusters were found to be well predicted by the Kelvin-Thomson relation pointing
      directly to the key step in the phase transition.

PMID- 22463543
TI  - Critical slowing down exponents of mode coupling theory.
AB  - A method is provided to compute the exponent parameter lambda yielding the
      dynamic exponents of critical slowing down in mode coupling theory. It is
      independent from the dynamic approach and based on the formulation of an
      effective static field theory. Expressions of lambda in terms of third order
      coefficients of the action expansion or, equivalently, in terms of six point
      cumulants are provided. Applications are reported to a number of mean-field
      models: with hard and soft variables and both fully connected and dilute
      interactions. Comparisons with existing results for the Potts glass model, the
      random orthogonal model, hard and soft-spin Sherrington-Kirkpatrick, and p-spin
      models are presented.

PMID- 22463544
TI  - High chalcocite Cu2S: a solid-liquid hybrid phase.
AB  - There are materials that exist in unusual solid-liquid hybrid phases, for
      example, the superionics at high temperatures of 700  degrees C. Using ab initio
      molecular dynamics, we show that the intensely studied Cu(2)S high chalcocite
      phase is actually a solid-liquid hybrid phase which exists in relatively low
      temperature (>105  degrees C). Its formation mechanism is different from the
      superionics. We also show that the previously proposed atomic structure for high
      chalcocite is incorrect, and the low chalcocite to high chalcocite transition
      should be described as a sublattice solid to liquid transition.

PMID- 22463545
TI  - Atomic force microscopy reveals bistable configurations of
      dibenzo[a,h]thianthrene and their interconversion pathway.
AB  - We investigated dibenzo[a,h]thianthrene molecules adsorbed on ultrathin layers of
      NaCl using a combined low-temperature scanning tunneling and atomic force
      microscope. Two stable configurations exist corresponding to different isomers of
      free nonplanar molecules. By means of excitations from inelastic electron
      tunneling we can switch between both configurations. Atomic force microscopy with
      submolecular resolution allows unambiguous determination of the molecular
      geometry, and the pathway of the interconversion of the isomers. Our
      investigations also shed new light on contrast mechanisms in scanning tunneling
      microscopy.

PMID- 22463546
TI  - Dimensional crossover driven by an electric field.
AB  - We study the steady-state dynamics of the Hubbard model driven out of equilibrium
      by a constant electric field and coupled to a dissipative heat bath. For a very
      strong field, we find a dimensional reduction: the system behaves as an
      equilibrium Hubbard model in lower dimensions. We derive steady-state equations
      for the dynamical mean-field theory in the presence of dissipation. We discuss
      how the electric field induced dimensional crossover affects the momentum
      resolved and integrated spectral functions, the energy distribution function, as
      well as the steady current in the nonlinear regime.

PMID- 22463547
TI  - Spin-selective Kondo insulator: cooperation of ferromagnetism and the Kondo
      effect.
AB  - We propose the notion of a spin-selective Kondo insulator, which provides a
      fundamental mechanism to describe the ferromagnetic phase of the Kondo lattice
      model with antiferromagnetic coupling. This unveils a remarkable feature of the
      ferromagnetic metallic phase: the majority-spin conduction electrons show
      metallic while the minority-spin electrons show insulating behavior. The
      resulting Kondo gap in the minority-spin sector, which is due to the cooperation
      of ferromagnetism and partial Kondo screening, evidences a dynamically induced
      commensurability for a combination of minority-spin electrons and parts of
      localized spins. Furthermore, this mechanism predicts a nontrivial relation
      between the macroscopic quantities such as electron magnetization, spin
      polarization, and electron filling.

PMID- 22463548
TI  - Ab initio studies on the interplay between spin-orbit interaction and Coulomb
      correlation in Sr2IrO4 and Ba2IrO4.
AB  - Ab initio analyses of A(2)IrO(4) (A=Sr,Ba) are presented. Effective Hubbard-type
      models for Ir 5d t(2g) manifolds downfolded from the global band structure are
      solved based on the dynamical mean-field theory. The results for A=Sr and Ba
      correctly reproduce paramagnetic metals undergoing continuous transitions to
      insulators below the Neel temperature T(N). These compounds are classified not
      into Mott insulators but into Slater insulators. However, the insulating gap
      opens by a synergy of the Neel order and significant band renormalization, which
      is also manifested by a 2D bad metallic behavior in the paramagnetic phase near
      the quantum criticality.

PMID- 22463549
TI  - Theory of a Fermi-liquid to non-Fermi-liquid quantum phase transition in
      dimensions d>1.
AB  - We develop a theory for a generic instability of a Fermi liquid in dimension d>1
      against the formation of a Luttinger-liquid-like state. The density of states at
      the Fermi level is the order parameter for the ensuing quantum phase transition,
      which is driven by the effective interaction strength. A scaling theory in
      conjunction with an effective field theory for clean electrons is used to obtain
      the critical behavior of observables. In the Fermi-liquid phase the order
      parameter susceptibility, which is measurable by tunneling, is predicted to
      diverge for 1<d<3.

PMID- 22463550
TI  - Two-channel Kondo physics in two-impurity Kondo models.
AB  - We consider the non-Fermi-liquid quantum critical state of the spin-S two
      impurity Kondo model and its potential realization in a quantum dot device. Using
      conformal field theory and the numerical renormalization group, we show the
      critical point to be identical to that of the two-channel Kondo model with
      additional potential scattering, for any spin S. Distinct conductance signatures
      are shown to arise as a function of device asymmetry, with the square-root
      behavior commonly believed to arise at low-energies dominant only in certain
      regimes.

PMID- 22463551
TI  - Interplay between nonequilibrium and equilibrium spin torque using synthetic
      ferrimagnets.
AB  - We discuss the current induced magnetization dynamics of spin valves F(0)|N|SyF
      where the free layer is a synthetic ferrimagnet SyF made of two ferromagnetic
      layers F(1) and F(2) coupled by RKKY exchange coupling. When the magnetic moment
      of the outer layer F(2) dominates the magnetization of the SyF, the sign of the
      effective spin torque exerted on the layer F(1) is controlled by the coupling's
      strength: for weak coupling the spin torque tends to antialign F(1)'s
      magnetization with respect to the pinned layer F(0). At large coupling the
      situation is reversed and tends to align F(1) with respect to F(0). At
      intermediate coupling, numerical simulations reveal that the competition between
      these two incompatible limits leads generically to spin torque oscillator (STO)
      behavior. The STO is found at zero magnetic field, with very significant
      amplitude of oscillations and frequencies up to 50 GHz or higher.

PMID- 22463552
TI  - Phonon-induced backscattering in helical edge states.
AB  - A single pair of helical edge states as realized at the boundary of a quantum
      spin Hall insulator is known to be robust against elastic single particle
      backscattering as long as time reversal symmetry is preserved. However, there is
      no symmetry preventing inelastic backscattering as brought about by phonons in
      the presence of Rashba spin orbit coupling. In this Letter, we show that the
      quantized conductivity of a single channel of helical Dirac electrons is
      protected even against this inelastic mechanism to leading order. We further
      demonstrate that this result remains valid when Coulomb interaction is included
      in the framework of a helical Tomonaga Luttinger liquid.

PMID- 22463553
TI  - Experimental demonstration of spin geometric phase: radius dependence of time
      reversal Aharonov-Casher oscillations.
AB  - A geometric phase of electron spin is studied in arrays of InAlAs/InGaAs two
      dimensional electron gas rings. By increasing the radius of the rings, the time
      reversal symmetric Aharonov-Casher oscillations of the electrical resistance are
      shifted towards weaker spin-orbit interaction regions with their shortened
      period. We conclude that the shift is due to a modulation of the spin geometric
      phase, the maximum modulation of which is approximately 1.5 rad. We further show
      that the Aharonov-Casher oscillations in various radius arrays collapse onto a
      universal curve if the radius and the strength of Rashba spin-orbit interaction
      are taken into account. The result is interpreted as the observation of the
      effective spin-dependent flux through a ring.

PMID- 22463554
TI  - Scaling of dynamical decoupling for spin qubits.
AB  - We investigate the scaling of coherence time T(2) with the number of pi pulses
      n(pi) in a singlet-triplet spin qubit using Carr-Purcell-Meiboom-Gill (CPMG) and
      concatenated dynamical decoupling (CDD) pulse sequences. For an even numbers of
      CPMG pulses, we find a power law T(2) is proportional to (n(pi))(gamma(e)), with
      gamma(e)=0.72+/-0.01, essentially independent of the envelope function used to
      extract T(2). From this surprisingly robust value, a power-law model of the noise
      spectrum of the environment, S(omega)~omega(-beta), yields beta=gamma(e)/(1
      gamma(e))=2.6+/-0.1. Model values for T(2)(n(pi)) using beta=2.6 for CPMG with
      both even and odd n(pi) up to 32 and CDD orders 3 through 6 compare very well
      with the experiment.

PMID- 22463555
TI  - Collective nature of the reentrant integer quantum Hall states in the second
      Landau level.
AB  - We report an unexpected sharp peak in the temperature dependence of the
      magnetoresistance of the reentrant integer quantum Hall states in the second
      Landau level. This peak defines the onset temperature of these states. We find
      that in different spin branches the onset temperatures of the reentrant states
      scale with the Coulomb energy. This scaling provides direct evidence that Coulomb
      interactions play an important role in the formation of these reentrant states
      evincing their collective nature.

PMID- 22463556
TI  - Competition for graphene: graphynes with direction-dependent Dirac cones.
AB  - The existence of Dirac cones in the band structure of two-dimensional materials
      accompanied by unprecedented electronic properties is considered to be a unique
      feature of graphene related to its hexagonal symmetry. Here, we present other two
      dimensional carbon materials, graphynes, that also possess Dirac cones according
      to first-principles electronic structure calculations. One of these materials,
      6,6,12-graphyne, does not have hexagonal symmetry and features two self-doped
      nonequivalent distorted Dirac cones suggesting electronic properties even more
      amazing than that of graphene.

PMID- 22463557
TI  - Effect of uniaxial strain on the structural and magnetic phase transitions in
      BaFe2As2.
AB  - We report neutron scattering experiments probing the influence of uniaxial strain
      on both the magnetic and structural order parameters in the parent iron pnictide
      compound, BaFe2As2. Our data show that modest strain fields along the in-plane
      orthorhombic b axis can affect significant changes in phase behavior simultaneous
      to the removal of structural twinning effects. As a result, we demonstrate in
      BaFe2As2 samples detwinned via uniaxial strain that the in-plane C4 symmetry is
      broken by both the structural lattice distortion and long-range spin ordering at
      temperatures far above the nominal (strain-free) phase transition temperatures.
      Surprising changes in the magnetic order parameter of this system under
      relatively small strain fields also suggest the inherent presence of magnetic
      domains fluctuating above the strain-free ordering temperature in this material.

PMID- 22463558
TI  - Vortex lattice studies in CeCoIn5 with H is orthogonal to c.
AB  - We present small angle neutron scattering studies of the vortex lattice (VL) in
      CeCoIn5 with magnetic fields applied parallel (H) to the antinodal [100] and
      nodal [110] directions. For H is parallel to [100], a single VL orientation is
      observed, while a 90 degrees  reorientation transition is found for H is parallel
      to [110]. For both field orientations and VL configurations we find a distorted
      hexagonal VL with an anisotropy, Gamma=2.0+/-0.05. The VL form factor shows
      strong Pauli paramagnetic effects similar to what have previously been reported
      for H is parallel to [001]. At high fields, above which the upper critical field
      (H(c2)) becomes a first-order transition, an increased disordering of the VL is
      observed.

PMID- 22463559
TI  - Evolution of edge states and critical phenomena in the Rashba superconductor with
      magnetization.
AB  - We study Andreev bound states (ABS) and the resulting charge transport of a
      Rashba superconductor (RSC) where two-dimensional semiconductor (2DSM)
      heterostructures are sandwiched by spin-singlet s-wave superconductor and
      ferromagnet insulator. ABS becomes a chiral Majorana edge mode in the topological
      phase (TP). We clarify two types of quantum criticality about the topological
      change of ABS near a quantum critical point (QCP), whether or not ABS exists at
      QCP. In the former type, ABS has an energy gap and does not cross at zero energy
      in the nontopological phase. These complex properties can be detected by
      tunneling conductance between normal metal-RSC junctions.

PMID- 22463524
TI  - J/psi polarization in pp collisions at ?s=7 TeV.
AB  - The ALICE Collaboration has studied J/psi production in pp collisions at ?s=7 TeV
      at the LHC through its muon pair decay. The polar and azimuthal angle
      distributions of the decay muons were measured, and results on the J/psi
      polarization parameters lambda(theta) and lambda(phi) were obtained. The study
      was performed in the kinematic region 2.5<y<4, 2<p(t)<8 GeV/c, in the helicity
      and Collins-Soper reference frames. In both frames, the polarization parameters
      are compatible with zero, within uncertainties.

PMID- 22463560
TI  - Quantification of correlations in quantum many-particle systems.
AB  - We introduce a well-defined and unbiased measure of the strength of correlations
      in quantum many-particle systems which is based on the relative von Neumann
      entropy computed from the density operator of correlated and uncorrelated states.
      The usefulness of this general concept is demonstrated by quantifying
      correlations of interacting electrons in the Hubbard model and in a series of
      transition-metal oxides using dynamical mean-field theory.

PMID- 22463561
TI  - Ba(1-x)K(x)Mn2As2: an antiferromagnetic local-moment metal.
AB  - The compound BaMn2As2 with the tetragonal ThCr2Si2 structure is a local-moment
      antiferromagnetic insulator with a Neel temperature T(N)=625 K and a large
      ordered moment MU=3.9MU(B)/Mn. We demonstrate that this compound can be driven
      metallic by partial substitution of Ba by K while retaining the same crystal and
      antiferromagnetic structures together with nearly the same high T(N) and large
      MU. Ba(1-x)K(x)Mn2As2 is thus the first metallic ThCr2Si2-type MAs-based system
      containing local 3d transition metal M magnetic moments, with consequences for
      the ongoing debate about the local-moment versus itinerant pictures of the FeAs
      based superconductors and parent compounds. The Ba(1-x)K(x)Mn2As2 class of
      compounds also forms a bridge between the layered iron pnictides and cuprates and
      may be useful to test theories of high T(c) superconductivity.

PMID- 22463562
TI  - Structural and magnetic dynamics of a laser induced phase transition in FeRh.
AB  - We use time-resolved x-ray diffraction and magneto-optical Kerr effect to study
      the laser-induced antiferromagnetic to ferromagnetic phase transition in FeRh.
      The structural response is given by the nucleation of independent ferromagnetic
      domains (tau(1)~30 ps). This is significantly faster than the magnetic response
      (tau(2)~60 ps) given by the subsequent domain realignment. X-ray diffraction
      shows that the two phases coexist on short time scales and that the phase
      transition is limited by the speed of sound. A nucleation model describing both
      the structural and magnetic dynamics is presented.

PMID- 22463563
TI  - Interface effects in perovskite thin films.
AB  - The control of matter properties (transport, magnetic, dielectric,...) using
      synthesis as thin films is strongly hindered by the lack of reliable theories,
      able to guide the design of new systems, through the understanding of the
      interface effects and of the way the substrate constraints are imposed on the
      material. The present Letter analyzes the energetic contributions at the
      interfaces, and proposes a model describing the microscopic mechanisms governing
      the interactions at an epitaxial interface between a manganite and another
      transition metal oxide in perovskite structure (as for instance SrTiO3). The
      model is checked against experimental results and literature analysis.

PMID- 22463564
TI  - Spin-resolved splitting of Kondo resonances in the presence of RKKY-type
      coupling.
AB  - We have performed spin-resolved measurements on a Kondo impurity in the presence
      of RKKY-type exchange coupling. By placing manganese phthalocyanine (MnPc)
      molecules on Fe-supported Pb islands, a Kondo system is devised which is exchange
      coupled to a magnetic substrate via conduction electrons in Pb, inducing spin
      splitting of the Kondo resonance. The spin-polarized nature of the split Kondo
      resonance and a spin filter effect induced by spin-flip inelastic electron
      tunneling are revealed by spin-polarized scanning tunneling microscopy and
      spectroscopy.

PMID- 22463565
TI  - Spin liquid phases for spin-1 systems on the triangular lattice.
AB  - Motivated by recent experiments on material Ba3NiSb2O9, we propose two novel spin
      liquid phases (A and B) for spin-1 systems on a triangular lattice. At the mean
      field level, both spin liquid phases have gapless fermionic spinon excitations
      with quadratic band touching; thus, in both phases the spin susceptibility and
      gamma=C(v)/T saturate to a constant at zero temperature, which are consistent
      with the experimental results on Ba3NiSb2O9. On the lattice scale, these spin
      liquid phases have Sp(4)~SO(5) gauge fluctuation, while in the long wavelength
      limit this Sp(4) gauge symmetry is broken down to U(1)*Z(2) in the type A spin
      liquid phase, and broken down to Z(4) in the type B phase. We also demonstrate
      that the A phase is the parent state of the ferroquadrupole state, nematic state,
      and the noncollinear spin density wave state.

PMID- 22463566
TI  - Conical spin-spiral state in an ultrathin film driven by higher-order spin
      interactions.
AB  - We report a transverse conical spin spiral as the magnetic ground state of a
      double-layer Mn on a W(110) surface. Using spin-polarized scanning tunneling
      microscopy, we find a long-range modulation along the [001] direction with a
      periodicity of 2.4 nm coexisting with a local row-wise antiferromagnetic
      contrast. First-principles calculations reveal a transverse conical spin-spiral
      ground state of this system which explains the observed magnetic contrast. The
      canting of the spins is induced by higher-order exchange interactions, while the
      spiraling along the [001] direction is due to frustrated Heisenberg exchange and
      Dzyaloshinskii-Moriya interaction.

PMID- 22463567
TI  - Nanoscale spin wave localization using ferromagnetic resonance force microscopy.
AB  - We use the dipolar fields from a magnetic cantilever tip to generate localized
      spin wave precession modes in an in-plane magnetized, thin ferromagnetic film.
      Multiple resonances from a series of localized modes are detected by
      ferromagnetic resonance force microscopy and reproduced by micromagnetic models
      that also reveal highly anisotropic mode profiles. Modeled scans of line defects
      using the lowest-frequency mode provide resolution predictions of (94.5+/-1.5) nm
      in the field direction, and (390+/-2) nm perpendicular to the field.

PMID- 22463568
TI  - Spin-flip limited exciton dephasing in CdSe/ZnS colloidal quantum dots.
AB  - The dephasing time of the lowest bright exciton in CdSe/ZnS wurtzite quantum dots
      is measured from 5 to 170 K and compared with density dynamics within the exciton
      fine structure using a sensitive three-beam four-wave-mixing technique unaffected
      by spectral diffusion. Pure dephasing via acoustic phonons dominates the initial
      dynamics, followed by an exponential zero-phonon line dephasing of 109 ps at 5 K,
      much faster than the ~10 ns exciton radiative lifetime. The zero-phonon line
      dephasing is explained by phonon-assisted spin flip from the lowest bright state
      to dark-exciton states. This is confirmed by the temperature dependence of the
      exciton lifetime and by direct measurements of the bright-dark-exciton
      relaxation. Our results give an unambiguous evidence of the physical origin of
      the exciton dephasing in these nanocrystals.

PMID- 22463569
TI  - Redshift of excitons in carbon nanotubes caused by the environment
      polarizability.
AB  - Optical excitations of molecular systems can be modified by their physical
      environment. We analyze the underlying mechanisms within many-body perturbation
      theory, which is particularly suited to study nonlocal polarizability effects on
      the electronic structure. Here we focus on the example of a semiconducting carbon
      nanotube, which observes redshifts of its excitons when the tube is touched by
      another nanotube or other physisorbates. We show that the redshifts mostly result
      from the polarizability of the attached ad system. Electronic coupling may
      enhance the redshifts, but depends very sensitively on the structural details of
      the contact.

PMID- 22463570
TI  - Terahertz response and colossal Kerr rotation from the surface states of the
      topological insulator Bi2Se3.
AB  - We report the THz response of thin films of the topological insulator Bi2Se3. At
      low frequencies, transport is essentially thickness independent showing the
      dominant contribution of the surface electrons. Despite their extended exposure
      to ambient conditions, these surfaces exhibit robust properties including narrow,
      almost thickness-independent Drude peaks, and an unprecedentedly large
      polarization rotation of linearly polarized light reflected in an applied
      magnetic field. This Kerr rotation can be as large as 65 degrees  and can be
      explained by a cyclotron resonance effect of the surface states.

PMID- 22463571
TI  - Ultrafast photocurrent measurement of the escape time of electrons and holes from
      carbon nanotube p-i-n photodiodes.
AB  - Ultrafast photocurrent measurements are performed on individual carbon nanotube p
      i-n photodiodes. The photocurrent response to subpicosecond pulses separated by a
      variable time delay Deltat shows strong photocurrent suppression when two pulses
      overlap (Deltat=0). The picosecond-scale decay time of photocurrent suppression
      scales inversely with the applied bias V(SD), and is twice as long for photon
      energy above the second subband E22 as compared to lower energy. The observed
      photocurrent behavior is well described by an escape time model that accounts for
      carrier effective mass.

PMID- 22463573
TI  - Persistence of surface domain structures for a bulk ferroelectric above TC.
AB  - Photoemission electron microscopy performed on a well-prepared surface of BaTiO3
      reveals the persistence of surface domains at temperatures well above the bulk
      Curie temperature. Their patterns follow the ferroelectric domain structure
      observed at 300 K. The contrast between formerly outward polarized domains and in
      plane polarized domains is preserved across the transition, while the contrast of
      inward polarized domains changes sign. The work functions of different possible
      structures are compared by first-principles calculations. The domain contrast in
      photoemission above the bulk Curie temperature is associated with a remaining
      tetragonal distortion of the topmost unit cells which is stabilized by an ionic
      surface relaxation.

PMID- 22463572
TI  - Ultrafast photovoltaic response in ferroelectric nanolayers.
AB  - We show that light drives large-amplitude structural changes in thin films of the
      prototypical ferroelectric PbTiO3 via direct coupling to its intrinsic
      photovoltaic response. Using time-resolved x-ray scattering to visualize atomic
      displacements on femtosecond time scales, photoinduced changes in the unit-cell
      tetragonality are observed. These are driven by the motion of photogenerated free
      charges within the ferroelectric and can be simply explained by a model including
      both shift and screening currents, associated with the displacement of electrons
      first antiparallel to and then parallel to the ferroelectric polarization
      direction.

PMID- 22463574
TI  - Tunable optical vortex arrays from a single nematic topological defect.
AB  - We report on the generation of tunable structured light fields endowed with
      various sets of phase singularities from a single topological defect in a nematic
      liquid crystal mesophase. The experimental demonstration relies on the use of
      electric field-induced nonsingular topological defects called "umbilics."

PMID- 22463575
TI  - Electric field induced phase transitions in polymers: a novel mechanism for high
      speed energy storage.
AB  - Using first-principles simulations, we identify the microscopic origin of the
      nonlinear dielectric response and high energy density of polyvinylidene-fluoride
      based polymers as a cooperative transition path that connects nonpolar and polar
      phases of the system. This path explores a complex torsional and rotational
      manifold and is thermodynamically and kinetically accessible at relatively low
      temperatures. Furthermore, the introduction of suitable copolymers significantly
      alters the energy barriers between phases providing tunability of both the energy
      density and the critical fields.

PMID- 22463576
TI  - Intermediate filaments in small configuration spaces.
AB  - Intermediate filaments play a key role in cell mechanics. Apart from their great
      importance from a biomedical point of view, they also act as a very suitable
      micrometer-sized model system for semiflexible polymers. We perform a statistical
      analysis of the thermal fluctuations of individual filaments confined in
      microchannels. The small channel width and the resulting deflections at the walls
      give rise to a reduction of the configuration space by about 2 orders of
      magnitude. This circumstance enables us to precisely measure the intrinsic
      persistence length of vimentin intermediate filaments and to show that they
      behave as ideal wormlike chains; we observe that small fluctuations in
      perpendicular planes decouple. Furthermore, the inclusion of results for confined
      actin filaments demonstrates that the Odijk confinement regime is valid over at
      least 1 order of magnitude in persistence length.

PMID- 22463577
TI  - Birth, death, and flight: a theory of Malthusian flocks.
AB  - I study "Malthusian flocks": moving aggregates of self-propelled entities (e.g.,
      organisms, cytoskeletal actin, microtubules in mitotic spindles) that reproduce
      and die. Long-ranged order (i.e., the existence of a nonzero average velocity
      (v(r,t))?0) is possible in these systems, even in spatial dimension d=2. Their
      spatiotemporal scaling structure can be determined exactly in d=2; furthermore,
      they lack both the longitudinal sound waves and the giant number fluctuations
      found in immortal flocks. Number fluctuations are very persistent, and propagate
      along the direction of flock motion, but at a different speed.

PMID- 22463578
TI  - Optimizing persistent random searches.
AB  - We consider a minimal model of persistent random searcher with a short range
      memory. We calculate exactly for such a searcher the mean first-passage time to a
      target in a bounded domain and find that it admits a nontrivial minimum as
      function of the persistence length. This reveals an optimal search strategy which
      differs markedly from the simple ballistic motion obtained in the case of Poisson
      distributed targets. Our results show that the distribution of targets plays a
      crucial role in the random search problem. In particular, in the biologically
      relevant cases of either a single target or regular patterns of targets, we find
      that, in strong contrast to repeated statements in the literature, persistent
      random walks with exponential distribution of excursion lengths can minimize the
      search time, and in that sense perform better than any Levy walk.

PMID- 22463579
TI  - Transport of long neutral polymers in the semidilute regime through a protein
      nanopore.
AB  - We investigate the entrance of single poly(ethylene glycol) chains into an alpha
      hemolysin channel. We detect the frequency and duration of the current blockades
      induced by large neutral polymers, where chain radius is larger than pore
      diameter. In the semidilute regime, these chains pass only if the monomer
      concentration is larger than a well-defined threshold. Experiments are performed
      in a very large domain of concentration and molecular mass, up to 35% and 200
      kDa, respectively, which was previously unexplored. The variation of the dwell
      time as a function of molecular mass shows that the chains are extracted from the
      semidilute solution in contact with the pore by a reptation mechanism.

PMID- 22463580
TI  - Connectedness percolation of elongated hard particles in an external field.
AB  - A theory is presented of how orienting fields and steric interactions conspire
      against the formation of a percolating network of, in some sense, connected
      elongated colloidal particles in fluid dispersions. We find that the network that
      forms above a critical loading breaks up again at higher loadings due to
      interaction-induced enhancement of the particle alignment. Upon approach of the
      percolation threshold, the cluster dimensions diverge with the same critical
      exponent parallel and perpendicular to the field direction, implying that
      connectedness percolation is not in the universality class of directed
      percolation.

PMID- 22463581
TI  - Nonaxisymmetric instability of shear-banded Taylor-Couette flow.
AB  - Recent experiments show that shear-banded flows of semidilute wormlike micelles
      in Taylor-Couette geometry exhibit a flow instability in the form of Taylor-like
      vortices. Here we perform the nonaxisymmetric linear stability analysis of the
      diffusive Johnson-Segalman model of shear banding and show that the nature of
      this instability depends on the applied shear rate. For the experimentally
      relevant parameters, we find that at the beginning of the stress plateau the
      instability is driven by the interface between the bands, while most of the
      stress plateau is occupied by the bulk instability of the high-shear-rate band.
      Our work significantly alters the recently proposed stability diagram of shear
      banded flows based on axisymmetric analysis.

PMID- 22463582
TI  - Decoupling of ionic transport from segmental relaxation in polymer electrolytes.
AB  - We present detailed studies of the relationship between ionic conductivity and
      segmental relaxation in polymer electrolytes. The analysis shows that the ionic
      conductivity can be decoupled from segmental dynamics and the strength of the
      decoupling correlates with the fragility but not with the glass transition
      temperature. These results call for a revision of the current picture of ionic
      transport in polymer electrolytes. We relate the observed decoupling phenomenon
      to frustration in packing of rigid polymers, where the loose local structure is
      also responsible for the increase in their fragility.

PMID- 22463583
TI  - Equilibrium strategy and population-size effects in lowest unique bid auctions.
AB  - In lowest unique bid auctions, N players bid for an item. The winner is whoever
      places the lowest bid, provided that it is also unique. We use a grand canonical
      approach to derive an analytical expression for the equilibrium distribution of
      strategies. We then study the properties of the solution as a function of the
      mean number of players, and compare them with a large data set of internet
      auctions. The theory agrees with the data with striking accuracy for small
      population-size N, while for larger N a qualitatively different distribution is
      observed. We interpret this result as the emergence of two different regimes, one
      in which adaptation is feasible and one in which it is not. Our results question
      the actual possibility of a large population to adapt and find the optimal
      strategy when participating in a collective game.

PMID- 22463585
TI  - Microvascular endoglin (CD105) expression correlates with tissue markers for
      atherosclerotic plaque vulnerability in an ageing population with multivessel
      coronary artery disease.
AB  - AIMS: Vulnerable atherosclerotic plaques are lesions with a high propensity to
      develop plaque disruption and superimposed thrombosis. No systematic studies have
      been carried out on tissue markers for plaque vulnerability throughout the entire
      coronary artery system at the end stages of coronary atherosclerosis. METHODS AND
      RESULTS: Nine autopsied patients (mean age 77 years) with angiographically severe
      trivascular coronary atherosclerosis were selected for this study. All visible
      lesions in postmortem coronary angiograms (n = 125) were histologically and
      immunohistochemically screened for the presence of intraplaque haemorrhages
      (activated) microvessels and inflammatory infiltrates. Intraplaque haemorrhages
      were observed in 76/125 plaques (61%). Chronic inflammation was found
      superficially in 59/125 plaques (47%) and deeply inside the plaque tissue in
      103/125 plaques (83%). Microvessels were found in 100/125 lesions (80%), of which
      58% showed endothelial expression of the vascular activation marker CD105.
      Moreover, microvascular CD105 positivity correlated positively with plaque
      haemorrhage and deeply seated plaque inflammation. CONCLUSIONS: Plaque
      inflammation and haemorrhages can be found at a high frequency throughout the
      coronary artery system of elderly patients with multivessel coronary
      atherosclerosis. Microvascular expression of endoglin (CD105), which correlates
      positively with both of these features of plaque vulnerability, can serve as a
      marker of the risk of developing coronary thrombotic complications.

PMID- 22463586
TI  - Pioglitazone prevents smoking carcinogen-induced lung tumor development in mice.
AB  - Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma
      (PPARgamma) ligand, is known to have anti-tumor activity by inducing tumor cell
      apoptosis. However, it is unknown whether it can be used to prevent smoking
      carcinogen-induced lung tumor development. We induced mouse lung tumors using
      smoking carcinogen 4- methylnitrosamino-l-3-pyridyl-butanone (NNK). PGZ was given
      at two early stages before the tumor formation. The role and the functional
      mechanism of PGZ were investigated in the development of mouse pulmonary tumors.
      The tumor development was monitored and PPARgamma activity and endogenous
      PPARgamma ligands 15(S)-HETE, 13(S)-HODE were determined. The application of PGZ
      before alveolar hyperplasia formation (Group NPa) and at the early phase of
      alveolar hyperplasia formation (Group NPb) significantly prevented the lung tumor
      development especially in Group NPb mice (all p < 0.05). PGZ not only prevented
      the NNK-mediated reduction of endogenous ligands 15(S)-HETE and 13(S)-HODE, but
      also increased 13(S)-HODE level in Group NPb mice. PPARgamma transcriptional
      activity was increased in NNKstimulated lung tissues when PGZ was given. The in
      vivo results were confirmed in the human lung cancer cells, which showed that PGZ
      induced lung cancer cell apoptosis through up-regulating nuclear PPARgamma
      expression, inducing PPARgamma transcriptional activity and increasing the levels
      of PPARgamma ligands in NNK-treated cells. The early application of PGZ is able
      to prevent NNK-induced lung tumor development through maintaining the level of
      endogenous PPARgamma ligands 15(S)-HETE and 13(S)-HODE and activation of
      PPARgamma.

PMID- 22463587
TI  - Inhibition of protein N-myristoylation: a therapeutic protocol in developing
      anticancer agents.
AB  - N-myristoyltransferase (NMT) is an essential eukaryotic enzyme which catalyzes
      the transfer of the myristoyl group to the terminal glycine residue of a number
      of proteins including those involved in signal transduction and apoptotic
      pathways. Myristoylation is crucial for the cellular proliferation process and is
      required for the growth and development in a number of organisms including many
      human pathogens and viruses. Targeting the myristoylation process thus has
      emerged as a novel therapeutic strategy for anticancer drug design. The
      expression/activity of NMT is considerably elevated in a number of cancers
      originating in the colon, stomach, gallbladder, brain and breast and attenuation
      of NMT levels has been shown to induce apoptosis in cancerous cell lines and
      reduce tumor volume in murine xenograft models for cancer. A focus of current
      therapeutic interventions in novel cancer treatments is therefore directed at
      developing specific NMT inhibitors. The inhibition of the myristoyl lipidation
      process with respect to cancer drug development lies in the fact that many
      proteins involved in oncogenesis such as src and various kinases require
      myristoylation to perform their cellular functions. Inhibiting NMT functions to
      control malignancy is a novel approach in the area of anticancer drug design and
      there are rapidly expanding discoveries of synthetic NMT inhibitors as potential
      chemotherapeutic agents to be employed in the warfare against cancer. The current
      review focuses on developments of various chemical NMT inhibitors with potential
      roles as anticancer agents.

PMID- 22463589
TI  - High CXCR4 expression correlates with sunitinib poor response in metastatic renal
      cancer.
AB  - BACKGROUND: Almost 30% of the sunitinib-treated patients for metastatic renal
      carcinoma (mRCC) do not receive a clinical benefit. Convincing evidences
      demonstrated a cross talk between the VEGF and CXCR4 pathways. It was
      hypothesized that CXCR4 expression in primary renal cancer could predict
      sunitinib responsiveness. PATIENTS AND METHODS: In this exploratory study sixty
      two mRCC patients receiving sunitinib as first-line treatment were evaluated for
      CXCR4 expression through immunohistochemistry (IHC). Correlations between CXCR4
      expression, baseline patients and tumour characteristics were studied by
      contingency tables and the chi-square test. Univariable analysis was performed
      with the log-rank test, and the Cox model was applied for multivariable analysis.
      RESULTS: The objective response rate of sunitinib first-line therapy was 35.5%
      (22/62) with a disease control rate (response and stable disease) of 62.9%
      (39/62). CXCR4 expression was absent/low in 30 (48.4%), moderate in 17 (27.4%),
      and high in 15 (24.2%) tumors respectively. Low or absent CXCR4 expression
      predicted response to sunitinib therapy. Moreover, Fuhrman grading and
      concomitant, CXCR4 and Fuhrman grading, strongly predicted sunitinib first line
      therapy responsiveness on progression-free survival and overall survival.
      CONCLUSIONS: High CXCR4 expression correlates with sunitinib poor response in
      metastatic renal cancer.

PMID- 22463590
TI  - Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of
      cyclin-dependent kinases and aurora kinases.
AB  - Aurora kinases and cyclin-dependent kinases, which play critical roles in the
      cell cycle and are frequently overexpressed in a variety of tumors, have been
      suggested as attractive targets for cancer therapy. JNJ-7706621, a recently
      identified dual inhibitor of these kinases, is reported to induce cell cycle
      arrest, endoreduplication, and apoptosis. In the present study, we further
      investigated the molecular mechanisms underlying these effects. The inhibitor
      arrested various cells at G2 phase at low concentration, and at both G1 and G2
      phases at high concentration. JNJ-7706621 did not prevent localization of Aurora
      A to the spindle poles, but did inhibit other centrosomal proteins such as TOG,
      Nek2, and TACC3 in early mitotic phase. Similarly, the drug did not prevent
      localization of Aurora B to the kinetochore, but did inhibit other chromosomal
      passenger proteins such as Survivin and INCENP. In the cells exposed to JNJ
      7706621 after nocodazole release, Aurora B, INCENP, and Survivin became relocated
      to the peripheral region of chromosomes, but Plk1 and Prc1 were localized on
      microtubules in later mitotic phase. Treatment of nocodazole-synchronized cells
      with JNJ-7706621 was able to override mitotic arrest by preventing spindle
      checkpoint signaling, resulting in failure of chromosome alignment and
      segregation. Injection of the drug significantly inhibited the growth of TC135
      Ewing's sarcoma cells transplanted into athymic mice by cell cycle arrest and
      apoptosis. JNJ-7706621 is a unique inhibitor regulating cell cycle progression at
      multiple points, suggesting that it could be useful for cell cycle analysis and
      therapy of various cancers, including Ewing's sarcoma.

PMID- 22463591
TI  - Lycopene modulation of molecular targets affected by smoking exposure.
AB  - Increasing evidence indicates that tomato lycopene may be an ideal candidate in
      protecting from cancer risk related to smoking exposure. The carotenoid shows
      potent redox-properties by which it decreases the reactive oxygen species (ROS)
      generated by smoke and modulates redox-sensitive cell targets, including protein
      tyrosine phosphatases, protein kinases, MAPKs and transcription factors.
      Moreover, it counteracts the effects of smoke on carcinogen-bioactivating enzymes
      and on molecular pathways involved in cell proliferation, apoptosis and
      inflammation. Lycopene also inhibits smoke-stimulated IGF-signalling and smoke
      induced DNA adducts. Some of these actions may be mediated by its oxidative
      metabolites and may be synergistically enhanced by the presence of other
      antioxidant nutrients. This review summarizes the background information about
      the interactions of lycopene with smoke in experimental models and presents the
      most current knowledge with respect to lycopene role in smoke-related diseases.

PMID- 22463588
TI  - Cyclooxygenase-2 (COX-2) mediates arsenite inhibition of UVB-induced cellular
      apoptosis in mouse epidermal Cl41 cells.
AB  - Inorganic arsenic is an environmental human carcinogen, and has been shown to act
      as a co-carcinogen with solar ultraviolet (UV) radiation in mouse skin tumor
      induction even at low concentrations. However, the precise mechanism of its co
      carcinogenic action is largely unknown. Apoptosis plays an essential role as a
      protective mechanism against neoplastic development in the organism by
      eliminating genetically damaged cells. Thus, suppression of apoptosis is thought
      to contribute to carcinogenesis. It is known that cyclooxygenase-2 (COX-2) can
      promote carcinogenesis by inhibiting cell apoptosis under stress conditions; and
      our current studies investigated the potential contribution of COX-2 to the
      inhibitory effect of arsenite in UV-induced cell apoptosis in mouse epidermal
      Cl41 cells. We found that treatment of cells with low concentration (5 MUM)
      arsenite attenuated cellular apoptosis upon UVB radiation accompanied with a
      coinductive effect on COX-2 expression and nuclear factor-kappaB (NFkappaB)
      transactivation. Our results also showed that the COX-2 induction by arsenite and
      UVB depended on an NFkappaB pathway because COX-2 co-induction could be
      attenuated in either p65-deficient or p50-deficient cells. Moreover, UVB-induced
      cell apoptosis could be dramatically reduced by the introduction of exogenous COX
      2 expression, whereas the inhibitory effect of arsenite on UVB-induced cell
      apoptosis could be impaired in COX-2 knockdown C141 cells. Our results indicated
      that COX-2 mediated the anti-apoptotic effect of arsenite in UVB radiation
      through an NFkappaB-dependent pathway. Given the importance of apoptosis evasion
      during carcinogenesis, we anticipated that COX-2 induction might be at least
      partially responsible for the co-carcinogenic effect of arsenite on UVB-induced
      skin carcinogenesis.

PMID- 22463592
TI  - Hip joint centre localisation with an unscented Kalman filter.
AB  - The accurate estimation of the hip joint centre (HJC) in gait analysis and in
      computer assisted orthopaedic procedures is a basic requirement. Functional
      methods, based on rigid body localisation, assessing the kinematics of the femur
      during circumduction movements (pivoting) have been used for estimating the HJC.
      Localising the femoral segment only, as it is usually done in total knee
      replacement procedure, can give rise to estimation errors, since the pelvis,
      during the passive pivoting manoeuvre, might undergo spatial displacements. This
      paper presents the design and test of an unscented Kalman filter that allows the
      estimation of the HJC by observing the pose of the femur and the 3D coordinates
      of a single marker attached to the pelvis. This new approach was validated using
      a hip joint mechanical simulator, mimicking both hard and soft tissues. The
      algorithm performances were compared with the literature standards and proved to
      have better performances in case of pelvis translation greater than 8 mm, thus
      satisfying the clinical requirements of the application.

PMID- 22463593
TI  - Spatiotemporal representation of cardiac vectorcardiogram (VCG) signals.
AB  - BACKGROUND: Vectorcardiogram (VCG) signals monitor both spatial and temporal
      cardiac electrical activities along three orthogonal planes of the body. However,
      the absence of spatiotemporal resolution in conventional VCG representations is a
      major impediment for medical interpretation and clinical usage of VCG. This is
      especially so because time-domain features of 12-lead ECG, instead of both
      spatial and temporal characteristics of VCG, are widely used for the automatic
      assessment of cardiac pathological patterns. MATERIALS AND METHODS: We present a
      novel representation approach that captures critical spatiotemporal heart
      dynamics by displaying the real time motion of VCG cardiac vectors in a 3D space.
      Such a dynamic display can also be realized with only one lead ECG signal (e.g.,
      ambulatory ECG) through an alternative lag-reconstructed ECG representation from
      nonlinear dynamics principles. Furthermore, the trajectories are color coded with
      additional dynamical properties of space-time VCG signals, e.g., the curvature,
      speed, octant and phase angles to enhance the information visibility. RESULTS: In
      this investigation, spatiotemporal VCG signal representation is used to
      characterize various spatiotemporal pathological patterns for healthy control
      (HC), myocardial infarction (MI), atrial fibrillation (AF) and bundle branch
      block (BBB). The proposed color coding scheme revealed that the spatial locations
      of the peak of T waves are in the Octant 6 for the majority (i.e., 74 out of 80)
      of healthy recordings in the PhysioNet PTB database. In contrast, the peak of T
      waves from 31.79% (117/368) of MI subjects are found to remain in Octant 6 and
      the rest (68.21%) spread over all other octants. The spatiotemporal VCG signal
      representation is shown to capture the same important heart characteristics as
      the 12-lead ECG plots and more. CONCLUSIONS: Spatiotemporal VCG signal
      representation is shown to facilitate the characterization of space-time cardiac
      pathological patterns and enhance the automatic assessment of cardiovascular
      diseases.

PMID- 22463594
TI  - Dynamic assembly of porphyrin wires trapped on a highly oriented pyrolitic
      graphite surface.
AB  - Carefully designed porphyrin building blocks assemble through selective imidazole
      binding in various solvents to form linear multiporphyrin objects. From a dynamic
      mixture of monomers, dimers, and oligomers, linear objects were observed on a
      highly oriented pyrolitic graphite (HOPG) surface. On the surface, the objects'
      morphology clearly depended on the solvent used for deposition and was modified
      upon heating.

PMID- 22463595
TI  - Comparison of key aroma compounds in five different types of Japanese soy sauces
      by aroma extract dilution analysis (AEDA).
AB  - An investigation by the aroma extract dilution analysis (AEDA) technique of the
      aroma concentrate from five different types of Japanese soy sauces, categorized
      according to Japan Agricultural Standards as Koikuchi Shoyu (KS), Usukuchi Shoyu
      (US), Tamari Shoyu (TS), Sai-Shikomi Shoyu (SSS), and Shiro Shoyu (SS), revealed
      25 key aroma compounds. Among them, 3-ethyl-1,2-cyclopentanedione and 2'
      aminoacetophenone were identified in the soy sauces for the first time. Whereas 3
      (methylthio)propanal (methional) and 3-hydroxy-4,5-dimethyl-2(5H)-furanone
      (sotolon) were detected in all of the soy sauce aroma concentrates as having high
      flavor dilution (FD) factors, 4-ethyl-2-methoxyphenol was detected as having a
      high FD factor in only four of the soy sauces (KS, US, TS, and SSS). Furthermore,
      5(or 2)-ethyl-4-hydroxy-2(or 5)-methyl-3(2H)-furanone (4-HEMF) and 4-hydroxy-2,5
      dimethyl-3(2H)-furanone (4-HDMF), which were thought to be the key odorants in
      KS, were detected in KS, US, TS, and SSS, but the FD factors widely varied among
      them. The sensory evaluations demonstrated that the aroma descriptions of a
      cooked potato-like note and a caramel-like/seasoning-like note were evaluated as
      high scores with no significant differences among the five soy sauces. On the
      other hand, a burnt/spicy note was evaluated as having high scores in KS, TS, and
      SSS, but it was evaluated as having a low score in SS. The comparative AEDA
      experiments and the auxiliary sensory experiments demonstrated that the five
      different types of Japanese soy sauces varied in their key aroma compounds and
      aroma characteristics, and the key aroma compounds in KS might not always be
      highly contributing in the other types of Japanese soy sauces.

PMID- 22463598
TI  - Nanoplasmonics for dual-molecule release through nanopores in the membrane of red
      blood cells.
AB  - A nanoplasmonics-based opto-nanoporation method of creating nanopores upon laser
      illumination is applied for inducing diffusion and triggered release of small and
      large molecules from red blood cells (RBCs). The method is implemented using
      absorbing gold nanoparticle (Au-NP) aggregates on the membrane of loaded RBCs,
      which, upon near-IR laser light absorption, induce release of encapsulated
      molecules from selected cells. The binding of Au-NPs to RBCs is characterized by
      Raman spectroscopy. The process of release is driven by heating localized at
      nanoparticles, which impacts the permeability of the membrane by affecting the
      lipid bilayer and/or trans-membrane proteins. Localized heating and temperature
      rise around Au-NP aggregates is simulated and discussed. Research reported in
      this work is relevant for generating nanopores for biomolecule trafficking
      through polymeric and lipid membranes as well as cell membranes, while dual- and
      multi-molecule release is relevant for theragnostics and a wide range of
      therapies.

PMID- 22463599
TI  - Photochemistry of furyl- and thienyldiazomethanes: spectroscopic characterization
      of triplet 3-thienylcarbene.
AB  - Photolysis (lambda > 543 nm) of 3-thienyldiazomethane (1), matrix isolated in Ar
      or N(2) at 10 K, yields triplet 3-thienylcarbene (13) and alpha-thial
      methylenecyclopropene (9). Carbene 13 was characterized by IR, UV/vis, and EPR
      spectroscopy. The conformational isomers of 3-thienylcarbene (s-E and s-Z)
      exhibit an unusually large difference in zero-field splitting parameters in the
      triplet EPR spectrum (|D/hc| = 0.508 cm(-1), |E/hc| = 0.0554 cm(-1); |D/hc| =
      0.579 cm(-1), |E/hc| = 0.0315 cm(-1)). Natural Bond Orbital (NBO) calculations
      reveal substantially differing spin densities in the 3-thienyl ring at the
      positions adjacent to the carbene center, which is one factor contributing to the
      large difference in D values. NBO calculations also reveal a stabilizing
      interaction between the sp orbital of the carbene carbon in the s-Z rotamer of 13
      and the antibonding sigma orbital between sulfur and the neighboring carbon-an
      interaction that is not observed in the s-E rotamer of 13. In contrast to the EPR
      spectra, the electronic absorption spectra of the rotamers of triplet 3
      thienylcarbene (13) are indistinguishable under our experimental conditions. The
      carbene exhibits a weak electronic absorption in the visible spectrum
      (lambda(max) = 467 nm) that is characteristic of triplet arylcarbenes. Although
      studies of 2-thienyldiazomethane (2), 3-furyldiazomethane (3), or 2
      furyldiazomethane (4) provided further insight into the photochemical
      interconversions among C(5)H(4)S or C(5)H(4)O isomers, these studies did not lead
      to the spectroscopic detection of the corresponding triplet carbenes (2
      thienylcarbene (11), 3-furylcarbene (23), or 2-furylcarbene (22), respectively).

PMID- 22463600
TI  - Association between irritable bowel syndrome and restless legs syndrome in the
      general population.
AB  - This study aimed to explore the association between restless legs syndrome and
      irritable bowel syndrome in an epidemiological cohort. We included 3365 adults,
      of whom 1602 were female (age 52.5 +/- 7.5 years), who had participated in the
      Korean Genome and Epidemiology Study (2005-2006). The diagnosis of restless legs
      syndrome was based on the criteria proposed by the International Restless Legs
      Syndrome Study Group, and irritable bowel syndrome was defined according to the
      Rome II criteria. The prevalence of each condition was determined and their
      association was tested by logistic regression analysis. Age, sex, haemoglobin
      concentration, renal insufficiency, use of medications and depressive mood were
      all adjusted for. The prevalence of restless legs syndrome and irritable bowel
      syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more
      prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P <
      0.001). Subjects with restless legs syndrome were older (54.2 +/- 8.4 versus 52.4
      +/- 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were
      predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia
      symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration
      (13.7 +/- 1.5 versus 14.1 +/- 1.6 g dL(-1) P = 0.004) and higher highly sensitive
      C-reactive protein (1.8 +/- 5.1 versus 1.4 +/- 2.9 mg dL(-1), P = 0.08). The
      adjusted odds ratio of restless legs syndrome in relation to irritable bowel
      syndrome was 2.59 (1.74-3.85, P < 0.001). Irritable bowel syndrome appeared to be
      associated with restless legs syndrome independently from other major risk
      factors for restless legs syndrome. Searching for the mechanisms underlying this
      association is indicated.

PMID- 22463601
TI  - Non-suicidal self-injury: state of the art perspective of a proposed new syndrome
      for DSM V.

PMID- 22463602
TI  - Normal diffusion-weighted MRI during the acute stage of central pontine
      myelinolysis.
AB  - Central pontine myelinolysis (CPM) is rare demyelinating disorder characterized
      by loss of myelin in the center of the basis pontis. The clinical features of CPM
      vary depending on the involved areas. Diffusion-weighted imaging (DWI) is thought
      to be useful for early detection during the acute phase, but its utility in this
      context has not been investigated thoroughly. We report the case of a CPM patient
      with normal initial DWI findings even at 1 week after symptom onset. To the best
      of our knowledge, no such cases of CPM have previously been reported.

PMID- 22463596
TI  - The impact of first year adherence to antiretroviral therapy on long-term
      clinical and immunological outcomes in the DART trial in Uganda and Zimbabwe.
AB  - OBJECTIVES: To describe associations between different summaries of adherence in
      the first year on antiretroviral therapy (ART) and the subsequent risk of
      mortality, to identify patients at high risk because of early adherence
      behaviour. METHODS: We previously described an approach where adherence behaviour
      at successive clinic visits during the first year on ART was seen as a Markov
      chain (MC), and the individually estimated transition probabilities between
      'good', 'poor' and 'non-response' adherence states were used to classify HIV
      infected adults in the DART trial into subgroups with similar behaviour. The
      impact of this classification and classifications based on traditional 'averaged'
      measures [mean drug possession ratio (DPR) and self-reported adherence] were
      compared in terms of their impact on longer-term mortality over the 2-5 years on
      ART using Cox proportional hazards models. RESULTS: Of 2960 participants in
      follow-up after 1 year on ART, 29% had never missed pills in the last month and
      11% had 100% DPR throughout the first year. The poorest adherers by self-reported
      measures were more likely to have only none/primary education (P < 0.01). Being
      in the poorest adherence subgroup by MC and DPR was independently associated with
      increased mortality [HR = 1.57 (95% CI 1.02, 2.42); 1.82 (1.32, 2.51)
      respectively]. CONCLUSIONS: Classification based on dynamic adherence behaviour
      is associated with mortality independently of DPR. The classifications could be
      useful in understanding adherence, targeting focused interventions and improving
      longer-term adherence to therapy.

PMID- 22463604
TI  - Langmuir. Biographical sketches.

PMID- 22463603
TI  - Ingesting a pre-workout supplement containing caffeine, B-vitamins, amino acids,
      creatine, and beta-alanine before exercise delays fatigue while improving
      reaction time and muscular endurance.
AB  - BACKGROUND: The purpose of this study was to determine the effects of the pre
      workout supplement AssaultTM (MusclePharm, Denver, CO, USA) on upper and lower
      body muscular endurance, aerobic and anaerobic capacity, and choice reaction time
      in recreationally-trained males. Subjective feelings of energy, fatigue,
      alertness, and focus were measured to examine associations between psychological
      factors and human performance. METHODS: Twelve recreationally-trained males
      participated in a 3-week investigation (mean +/- SD, age: 28 +/- 5 y, height: 178
      +/- 9 cm, weight: 79.2 +/- 15.7 kg, VO2max: 45.7 +/- 7.6 ml/kg/min). Subjects
      reported to the human performance laboratory on three separate occasions. All
      participants completed a baseline/familiarization day of testing that included a
      maximal graded exercise test for the determination of aerobic capacity (VO2max),
      one-rep maximum (1-RM) for bench and leg press to determine 75% of 1-RM, choice
      reaction tests, and intermittent critical velocity familiarization. Choice
      reaction tests included the following: single-step audio and visual, one-tower
      stationary protocol, two-tower lateral protocol, three-tower multi-directional
      protocol, and three-tower multi-directional protocol with martial arts sticks.
      Subjects were randomly assigned to ingest either the supplement (SUP) or the
      placebo (PL) during Visit 2. Subjects were provided with the cross-over treatment
      on the last testing visit. Testing occurred 20 min following ingestion of both
      treatments. RESULTS: Significant (p < 0.05) main effects for the SUP were
      observed for leg press (SUP: 13 +/- 6 reps, PL: 11 +/- 3 reps), perceived energy
      (SUP: 3.4 +/- 0.9, PL: 3.1 +/- 0.8), alertness (SUP: 4.0 +/- 0.7, PL: 3.5 +/-
      0.8), focus (SUP: 4.1 +/- 0.6, PL: 3.5 +/- 0.8), choice reaction audio single
      step (SUP: 0.92 +/- 0.10 s, PL: 0.97 +/- 0.11 s), choice reaction multi-direction
      15 s (SUP: 1.07 +/- 0.12 s, PL: 1.13 +/- 0.14 s), and multi-direction for 30 s
      (SUP: 1.10 +/- 0.11 s, PL: 1.14 +/- 0.13 s). CONCLUSIONS: Ingesting the SUP
      before exercise significantly improved agility choice reaction performance and
      lower body muscular endurance, while increasing perceived energy and reducing
      subjective fatigue. These findings suggest that the SUP may delay fatigue during
      strenuous exercise.

PMID- 22463605
TI  - Age your garlic for longevity!

PMID- 22463606
TI  - Potent biomechanical and molecular behaviour of cardiac adipose tissue during
      cardiopulmonary resuscitation and post-resuscitation period.

PMID- 22463607
TI  - The juxtaglomerular apparatus.

PMID- 22463608
TI  - Phospholamban and cardiac function: a comparative perspective in vertebrates.
AB  - Phospholamban (PLN) is a small phosphoprotein closely associated with the cardiac
      sarcoplasmic reticulum (SR). Dephosphorylated PLN tonically inhibits the SR Ca
      ATPase (SERCA2a), while phosphorylation at Ser16 by PKA and Thr17 by Ca(2+)
      /calmodulin-dependent protein kinase (CaMKII) relieves the inhibition, and this
      increases SR Ca(2+) uptake. For this reason, PLN is one of the major determinants
      of cardiac contractility and relaxation. In this review, we attempted to
      highlight the functional significance of PLN in vertebrate cardiac physiology. We
      will refer to the huge literature on mammals in order to describe the molecular
      characteristics of this protein, its interaction with SERCA2a and its role in the
      regulation of the mechanic and the electric performance of the heart under basal
      conditions, in the presence of chemical and physical stresses, such as beta
      adrenergic stimulation, response to stretch, force-frequency relationship and
      intracellular acidosis. Our aim is to provide the basis to discuss the role of
      PLN also on the cardiac function of nonmammalian vertebrates, because so far this
      aspect has been almost neglected. Accordingly, when possible, the literature on
      PLN will be analysed taking into account the nonuniform cardiac structural and
      functional characteristics encountered in ectothermic vertebrates, such as the
      peculiar and variable organization of the SR, the large spectrum of response to
      stresses and the disaptive absence of crucial proteins (i.e. haemoglobinless and
      myoglobinless species).

PMID- 22463609
TI  - Physiological regulation of cardiac contractility by endogenous reactive oxygen
      species.
AB  - Increased production of reactive oxygen species (ROS) has been linked to the
      pathogenesis of congestive heart failure. However, emerging evidence suggests the
      involvement of ROS in the regulation of various physiological cellular processes
      in the myocardium. In this review, we summarize the latest findings regarding the
      role of ROS in the acute regulation of cardiac contractility. We discuss ROS
      dependent modulation of the inotropic responses to G protein-coupled receptor
      agonists (e.g. beta-adrenergic receptor agonists and endothelin-1), the potential
      cellular sources of ROS (e.g. NAD(P)H oxidases and mitochondria) and the proposed
      end-targets and signalling pathways by which ROS affect contractility.
      Accumulating new data supports the fundamental role of endogenously generated ROS
      to regulate cardiac function under physiological conditions.

PMID- 22463610
TI  - CB1 receptor antagonists: new discoveries leading to new perspectives.
AB  - CB(1)  receptor antagonists were among the most promising drug targets in the
      last decade. They have been explored and found to be effective as therapeutic
      agents for obesity and related cardiometabolic problems; however, use of
      rimonabant, the first marketed CB(1)  receptor antagonist, has been suspended
      because of its anxiogenic and depressogenic side effects. Because some other
      antiobesity drugs, like dexfenfluramine or sibutramine, were also suspended, the
      unmet need for drugs that reduce body weight became enormous. One approach that
      emerged was the use of CB(1)  receptor antagonists that poorly cross the blood
      brain barrier, the second, the development of neutral antagonists instead of
      inverse agonists, and the third, use of personalized medicine, namely the
      selection of the patient population without psychiatric side effects. In this
      review, we dissect the peripheral and central mechanisms involved in the effects
      of CB(1)  receptor antagonists and argue that central mechanisms are more or less
      involved in most cardiometabolic therapeutic effects and thus, among patients
      with unsatisfactory therapeutic response to compounds with peripheral action,
      centrally acting antagonists may be needed. An analysis of pharmacogenetic
      factors may help to identify persons who are at no or low risk for psychiatric
      adverse effects. Here, we present the models and identify molecular mechanisms
      and receptors involved in the effects of stress-, anxiety- and depression-related
      neurocircuitries sensitive to CB(1)  receptor antagonists, like the serotonergic,
      noradrenergic and dopaminergic systems, which are not only regulated by CB(1) 
      receptors, but also regulate the synthesis of the endocannabinoid 2-arachidonoyl
      glycerol.

PMID- 22463611
TI  - Caffeine-stimulated fatty acid oxidation is blunted in CD36 null mice.
AB  - AIM: The increase in skeletal muscle fatty acid metabolism during exercise has
      been associated with the release of calcium. We examined whether this increase in
      fatty acid oxidation was attributable to a calcium-induced translocation of the
      fatty acid transporter CD36 to the sarcolemma, thereby providing an enhanced
      influx of fatty acids to increase their oxidation. METHODS: Calcium release was
      triggered by caffeine (3 mm) to examine fatty acid oxidation in intact soleus
      muscles of WT and CD36-KO mice, while fatty acid transport and mitochondrial
      fatty acid oxidation were examined in giant vesicles and isolated mitochondria,
      respectively, from caffeine-perfused hindlimb muscles of WT and CD36-KO mice.
      Western blotting was used to examine calcium-induced signalling. RESULTS: In WT,
      caffeine stimulated muscle palmitate oxidation (+136%), but this was blunted in
      CD36-KO mice (-70%). Dantrolene inhibited (WT) or abolished (CD36-KO) caffeine
      induced palmitate oxidation. In muscle, caffeine-stimulated palmitate oxidation
      was not attributable to altered mitochondrial palmitate oxidation. Instead, in
      WT, caffeine increased palmitate transport (+55%) and the translocation of fatty
      acid transporters CD36, FABPpm, FATP1 and FATP4 (26-70%) to the sarcolemma. In
      CD36-KO mice, caffeine-stimulated FABPpm, and FATP1 and 4 translocations were
      normal, but palmitate transport was blunted (-70%), comparable to the reductions
      in muscle palmitate oxidation. Caffeine did not alter the calcium-/calmodulin
      dependent protein kinase II phosphorylation but did increase the phosphorylation
      of AMPK and acetyl-CoA carboxylase comparably in WT and CD36-KO. CONCLUSION:
      These studies indicate that sarcolemmal CD36-mediated fatty acid transport is a
      primary mediator of the calcium-induced increase in muscle fatty acid oxidation.

PMID- 22463613
TI  - X-Ray Photoelectron Spectroscopy Study of MoCl(2)(NO)(2)(P(C(6)H(5))(3))(2).

PMID- 22463612
TI  - Chronic endothelin A receptor blockade attenuates contribution of sympathetic
      nervous system to salt hypertension development in adult but not in young Dahl
      rats.
AB  - AIM: Endothelin-1 (ET-1) plays an important role in the pathogenesis of salt
      dependent forms of hypertension in adult rats, but its participation in salt
      hypertension elicited in immature rats is still unknown. Therefore, we compared
      ET-1 role in the development or the maintenance of salt hypertension induced in
      young (4-week-old) or adult (12-week-old) Dahl rats. METHODS: The contribution of
      pressor ET-1 effects to the maintenance of high blood pressure (BP) was studied
      using acute injection of ET(A) receptor antagonist ambrisentan (BSF 208075, 1 mg
      kg(-1) iv) to young or adult rats with established salt hypertension.
      Furthermore, using chronic ambrisentan treatment (30 mg kg(-1) day(-1) in the
      drinking fluid during 5 weeks of high salt intake), we investigated the age
      dependent involvement of ET(A) receptors in salt hypertension development in
      these two age groups. RESULTS: Acute ET(A) receptor blockade lowered BP in both
      age groups of salt hypertensive Dahl rats more than in rats fed a low-salt diet
      (but without any age-dependent difference). Chronic ET(A) receptor blockade
      strongly attenuated the development of salt hypertension and cardiac hypertrophy
      in adult rats, but it had no significant effects on salt hypertension in young
      animals. Pronounced BP reduction induced in adult salt hypertensive rats by
      chronic ambrisentan treatment was attributed to attenuated sympathetic BP
      component, without changes in nitric oxide (NO)-dependent BP regulation. In
      contrast, chronic ambrisentan treatment of young animals did not modify
      sympathetic BP component but substantially attenuated NO-dependent
      vasodilatation. CONCLUSIONS: ET(A) receptor-mediated ET-1 effects play an
      important role in salt hypertension of adult but not young Dahl rats.

PMID- 22463615
TI  - Response to waste electrical and electronic equipments in China: legislation,
      recycling system, and advanced integrated process.
AB  - Over the past 30 years, China has been suffering from negative environmental
      impacts from distempered waste electrical and electronic equipments (WEEE)
      recycling activities. For the purpose of environmental protection and resource
      reusing, China made a great effort to improve WEEE recycling. This article
      reviews progresses of three major fields in the development of China's WEEE
      recycling industry: legal system, formal recycling system, and advanced
      integrated process. Related laws concerning electronic waste (e-waste) management
      and renewable resource recycling are analyzed from aspects of improvements and
      loopholes. The outcomes and challenges for existing formal recycling systems are
      also discussed. The advantage and deficiency related to advanced integrated
      recycling processes for typical e-wastes are evaluated respectively. Finally, in
      order to achieve high disposal rates of WEEE, high-quantify separation of
      different materials in WEEE and high added value final products produced by
      separated materials from WEEE, an idea of integrated WEEE recycling system is
      proposed to point future development of WEEE recycling industry.

PMID- 22463614
TI  - Refining the value of secretory phospholipase A2 as a predictor of acute chest
      syndrome in sickle cell disease: results of a feasibility study (PROACTIVE).
AB  - Acute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new
      pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half
      of ACS episodes occur in SCD patients already hospitalized, potentially
      permitting pre-emptive therapy in high-risk patients. Simple transfusion of red
      blood cells may abort ACS if given to patients hospitalized for pain who develop
      fever and elevated levels of secretory phospholipase A2 (sPLA2). In a feasibility
      study (PROACTIVE; ClinicalTrials.gov NCT00951808), patients hospitalized for pain
      who developed fever and elevated sPLA2 were eligible for randomization to
      transfusion or observation; all others were enrolled in an observational arm. Of
      237 enrolled, only 10 were randomized; one of the four to receive transfusion had
      delayed treatment. Of 233 subjects receiving standard care, 22 developed ACS. A
      threshold level of sPLA2 >= 48 ng/ml gave optimal sensitivity (73%), specificity
      (71%) and accuracy (71%), but a positive predictive value of only 24%. The
      predictive value of sPLA2 was improved in adults and patients with chest or back
      pain, lower haemoglobin concentration and higher white blood cell counts, and in
      those receiving less than two-thirds maintenance fluids. The hurdles identified
      in PROACTIVE should facilitate design of a larger, definitive, phase 3 randomized
      controlled trial.

PMID- 22463616
TI  - Healthcare resource use in advanced prostate cancer patients treated with
      docetaxel.
AB  - OBJECTIVE: Although the treatment of metastatic castrate-resistant prostate
      cancer (mCRPC) has improved with newer therapies, there is little understanding
      how these therapies have impacted resource use and associated expenditures;
      available estimates are dated. The current study examined contemporary healthcare
      utilization and associated costs for mCRPC patients and how these measures
      changed over time. METHODS: This retrospective cohort analysis used medical and
      pharmaceutical insurance claims data from a large non-payer-owned integrated
      claims database of US commercial insurers. Amongst all patients with a prostate
      cancer diagnosis (n=256,464), those with >= 1 docetaxel claim (docetaxel cohort,
      n=3642) were identified as mCRPC patients. Within the docetaxel cohort, an
      additional 6-months follow-up cohort (n=2862) was identified, i.e., patients with
      at least 6 months of follow-up after the first docetaxel claim. Resource
      utilization and costs were identified for all-cause hospitalizations, emergency
      room (ER) visits, physician visits and ambulatory visits, and prostate cancer
      related prescription treatments. RESULTS: Significant increases in the mean per
      patient-per-month (PPPM) count for the docetaxel cohort were observed for all
      medical resources measured (hospitalizations and ER, physician, and ambulatory
      visits) in the post-docetaxel period compared with the pre-docetaxel period
      (p<0.0001); similar significant increases were observed for the 6-months follow
      up cohort in the last 6 months (prior to lost to follow-up date) compared with
      the period preceding the last 6 months (p<0.0408 ambulatory visits, p<0.0001 all
      other resources). Total docetaxel cohort costs (mean [standard deviation]) rose
      from an average PPPM cost of US$2593 (3208) in the pre-docetaxel period to
      US$5847 (6990) in the post-docetaxel period (p<0.0001); each of the individual
      resources measured (hospitalization, all healthcare visits, and prescription
      costs) demonstrated significant increases (p<0.0001). LIMITATIONS: Retrospective
      study design. CONCLUSIONS: This large database analysis showed a significant
      increase in use of healthcare resources and associated costs among mCRPC patients
      following first-line docetaxel treatment.

PMID- 22463617
TI  - Inverse Ising inference using all the data.
AB  - We show that a method based on logistic regression, using all the data, solves
      the inverse Ising problem far better than mean-field calculations relying only on
      sample pairwise correlation functions, while still computationally feasible for
      hundreds of nodes. The largest improvement in reconstruction occurs for strong
      interactions. Using two examples, a diluted Sherrington-Kirkpatrick model and a
      two-dimensional lattice, we also show that interaction topologies can be
      recovered from few samples with good accuracy and that the use of l(1)
      regularization is beneficial in this process, pushing inference abilities further
      into low-temperature regimes.

PMID- 22463618
TI  - Effect of light assisted collisions on matter wave coherence in superradiant Bose
      Einstein condensates.
AB  - We investigate experimentally the effects of light assisted collisions on the
      coherence between momentum states in Bose-Einstein condensates. The onset of
      superradiant Rayleigh scattering serves as a sensitive monitor for matter-wave
      coherence. A subtle interplay of binary and collective effects leads to a
      profound asymmetry between the two sides of the atomic resonance and provides far
      bigger coherence loss rates for a condensate bathed in blue detuned light than
      previously estimated. We present a simplified quantitative model containing the
      essential physics to explain our experimental data and point at a new
      experimental route to study strongly coupled light matter systems.

PMID- 22463619
TI  - Influence of the Coriolis force in atom interferometry.
AB  - In a light-pulse atom interferometer, we use a tip-tilt mirror to remove the
      influence of the Coriolis force from Earth's rotation and to characterize
      configuration space wave packets. For interferometers with a large momentum
      transfer and large pulse separation time, we improve the contrast by up to 350%
      and suppress systematic effects. We also reach what is to our knowledge the
      largest space-time area enclosed in any atom interferometer to date. We discuss
      implications for future high-performance instruments.

PMID- 22463620
TI  - Experimental observation of impossible-to-beat quantum advantage on a hybrid
      photonic system.
AB  - Quantum resources outperform classical ones for certain communication and
      computational tasks. Remarkably, in some cases, the quantum advantage cannot be
      improved using hypothetical postquantum resources. A class of tasks with this
      property can be singled out using graph theory. Here we report the experimental
      observation of an impossible-to-beat quantum advantage on a four-dimensional
      quantum system defined by the polarization and orbital angular momentum of a
      single photon. The results show pristine evidence of the quantum advantage and
      are compatible with the maximum advantage allowed using postquantum resources.

PMID- 22463621
TI  - High-accuracy optical clock based on the octupole transition in 171Yb+.
AB  - We experimentally investigate an optical frequency standard based on the 467 nm
      (642 THz) electric-octupole reference transition (2)S(1/2)(F=0)->(2)F(7/2)(F=3)
      in a single trapped (171)Yb(+) ion. The extraordinary features of this transition
      result from the long natural lifetime and from the 4f(13)6s(2) configuration of
      the upper state. The electric-quadrupole moment of the (2)F(7/2) state is
      measured as -0.041(5)ea(0)(2), where e is the elementary charge and a(0) the Bohr
      radius. We also obtain information on the differential scalar and tensorial
      components of the static polarizability and of the probe-light-induced ac Stark
      shift of the octupole transition. With a real-time extrapolation scheme that
      eliminates this shift, the unperturbed transition frequency is realized with a
      fractional uncertainty of 7.1*10(-17). The frequency is measured as 642 121 496
      772 645.15(52) Hz.

PMID- 22463622
TI  - Measuring a cosmological distance-redshift relationship using only gravitational
      wave observations of binary neutron star coalescences.
AB  - Detection of gravitational waves from the inspiral phase of binary neutron star
      coalescence will allow us to measure the effects of the tidal coupling in such
      systems. Tidal effects provide additional contributions to the phase evolution of
      the gravitational wave signal that break a degeneracy between the system's mass
      parameters and redshift and thereby allow the simultaneous measurement of both
      the effective distance and the redshift for individual sources. Using the
      population of O(10(3)-10(7)) detectable binary neutron star systems predicted for
      3rd generation gravitational wave detectors, the luminosity distance-redshift
      relation can be probed independently of the cosmological distance ladder and
      independently of electromagnetic observations. We conclude that for a range of
      representative neutron star equations of state the redshift of such systems can
      be determined to an accuracy of 8%-40% for z<1 and 9%-65% for 1<z<4.

PMID- 22463623
TI  - Probing the interiors of the ice giants: shock compression of water to 700 GPa
      and 3.8 g/cm3.
AB  - Recently, there has been a tremendous increase in the number of identified
      extrasolar planetary systems. Our understanding of their formation is tied to
      exoplanet internal structure models, which rely upon equations of state of light
      elements and compounds such as water. Here, we present shock compression data for
      water with unprecedented accuracy that show that water equations of state
      commonly used in planetary modeling significantly overestimate the
      compressibility at conditions relevant to planetary interiors. Furthermore, we
      show that its behavior at these conditions, including reflectivity and isentropic
      response, is well-described by a recent first-principles based equation of state.
      These findings advocate that this water model be used as the standard for
      modeling Neptune, Uranus, and "hot Neptune" exoplanets and should improve our
      understanding of these types of planets.

PMID- 22463624
TI  - Physical process first law and increase of horizon entropy for black holes in
      Einstein-Gauss-Bonnet gravity.
AB  - We establish the physical process version of the first law by studying small
      perturbations of a stationary black hole with a regular bifurcation surface in
      Einstein-Gauss-Bonnet gravity. Our result shows that when the stationary black
      hole is perturbed by a matter stress energy tensor and finally settles down to a
      new stationary state, the Wald entropy increases as long as the matter satisfies
      the null energy condition.

PMID- 22463625
TI  - Spin-density matrix elements for gammap->K*0Sigma+ at Egamma=1.85-3.0 GeV with
      evidence for the kappa(800) meson exchange.
AB  - The exclusive reaction gammap->K(+)pi(-)Sigma(+) was measured for the first time
      using linearly polarized photons at beam energies from 1.85 to 2.96 GeV. Angular
      distributions in the rest frame of the K(+)pi(-) system were fitted to extract
      spin-density matrix elements of the K(*0) decay. The measured parity spin
      asymmetry shows that natural-parity exchange is dominant in this reaction. This
      result clearly indicates the need for t-channel exchange of the kappa(800) scalar
      meson.

PMID- 22463627
TI  - Self-consistent tilted-axis-cranking study of triaxial strongly deformed bands in
      158Er at ultrahigh spin.
AB  - Stimulated by recent experimental discoveries, triaxial strongly deformed (TSD)
      states in (158)Er at ultrahigh spins have been studied by means of the Skyrme
      Hartree-Fock model and the tilted-axis-cranking method. Restricting the
      rotational axis to one of the principal axes--as done in previous cranking
      calculations--two well-defined TSD minima in the total Routhian surface are found
      for a given configuration: one with positive and another with negative triaxial
      deformation gamma. By allowing the rotational axis to change direction, the
      higher-energy minimum is shown to be a saddle point. This resolves the long
      standing question of the physical interpretation of the two triaxial minima at a
      very similar quadrupole shape obtained in the principal-axis-cranking approach.
      Several TSD configurations have been predicted, including a highly deformed band,
      which is a candidate for the structure observed in experiment.

PMID- 22463629
TI  - Amplitude and phase reconstruction of electron wave packets for probing ultrafast
      photoionization dynamics.
AB  - Ultrafast atomic processes, such as excitation and ionization occurring on the
      femtosecond or shorter time scale, were explored by employing attosecond high
      harmonic pulses. With the absorption of a suitable high-harmonic photon a He atom
      was ionized, or resonantly excited with further ionization by absorbing a number
      of infrared photons. The electron wave packets liberated by the two processes
      generated an interference containing the information on ultrafast atomic
      dynamics. The attosecond electron wave packet, including the phase, from the
      ground state was reconstructed first and, subsequently, that from the 1s3p state
      was retrieved by applying the holographic technique to the photoelectron spectra
      comprising the interference between the two ionization paths. The reconstructed
      electron wave packet revealed details of the ultrafast photoionization dynamics,
      such as the instantaneous two-photon ionization rate.

PMID- 22463628
TI  - New measurements of high-momentum nucleons and short-range structures in nuclei.
AB  - We present new measurements of electron scattering from high-momentum nucleons in
      nuclei. These data allow an improved determination of the strength of two-nucleon
      correlations for several nuclei, including light nuclei where clustering effects
      can, for the first time, be examined. The data also include the kinematic region
      where three-nucleon correlations are expected to dominate.

PMID- 22463630
TI  - Observation of anomalous diffusion and fractional self-similarity in one
      dimension.
AB  - We experimentally study anomalous diffusion of ultracold atoms in a one
      dimensional polarization optical lattice. The atomic spatial distribution is
      recorded at different times and its dynamics and shape are analyzed. We find that
      the width of the cloud exhibits a power-law time dependence with an exponent that
      depends on the lattice depth. Moreover, the distribution exhibits fractional self
      similarity with the same characteristic exponent. The self-similar shape of the
      distribution is found to be well fitted by a Levy distribution, but with a
      characteristic exponent that differs from the temporal one. Numerical simulations
      suggest that this is due to long trapping times in the lattice and correlations
      between the atom's velocity and flight duration.

PMID- 22463631
TI  - Ubiquitous nature of multimode vibrational resonances in positron-molecule
      annihilation.
AB  - Positron annihilation on many molecules occurs via positron capture into
      vibrational Feshbach resonances, with annihilation rates often further enhanced
      by energy transfer to vibrational excitations weakly coupled to the positron
      continuum. Data presented here uncover another scenario in which the positron
      couples directly to a quasicontinuum of multimode vibrational states. A model
      that assumes excitation and escape from a statistically complete ensemble of
      multimode vibrations is presented that reproduces key features of the data.

PMID- 22463632
TI  - Ultrafast x-ray scattering of xenon nanoparticles: imaging transient states of
      matter.
AB  - Femtosecond x-ray laser flashes with power densities of up to 10(14) W/cm(2) at
      13.7 nm wavelength were scattered by single xenon clusters in the gas phase.
      Similar to light scattering from atmospheric microparticles, the x-ray
      diffraction patterns carry information about the optical constants of the
      objects. However, the high flux of the x-ray laser induces severe transient
      changes of the electronic configuration, resulting in a tenfold increase of
      absorption in the developing nanoplasma. The modification in opaqueness can be
      correlated to strong atomic charging of the particle leading to excitation of
      Xe(4+). It is shown that single-shot single-particle scattering on femtosecond
      time scales yields insight into ultrafast processes in highly excited systems
      where conventional spectroscopy techniques are inherently blind.

PMID- 22463633
TI  - Single-photon spectroscopy of a single molecule.
AB  - Efficient interaction of light and matter at the ultimate limit of single photons
      and single emitters is of great interest from a fundamental point of view and for
      emerging applications in quantum engineering. However, the difficulty of
      generating single-photon streams with specific wavelengths, bandwidths, and power
      as well as the weak interaction probability of a single photon with an optical
      emitter pose a formidable challenge toward this goal. Here, we demonstrate a
      general approach based on the creation of single photons from a single emitter
      and their use for performing spectroscopy on a second emitter situated at a
      distance. While this first proof of principle realization uses organic molecules
      as emitters, the scheme is readily extendable to quantum dots and color centers.
      Our work ushers in a new line of experiments that provide access to the coherent
      and nonlinear couplings of few emitters and few propagating photons.

PMID- 22463634
TI  - Subnatural linewidth single photons from a quantum dot.
AB  - The observation of quantum-dot resonance fluorescence enabled a new solid-state
      approach to generating single photons with a bandwidth approaching the natural
      linewidth of a quantum-dot transition. Here, we operate in the small Rabi
      frequency limit of resonance fluorescence--the Heitler regime--to generate
      subnatural linewidth and high-coherence quantum light from a single quantum dot.
      The measured single-photon coherence is 30 times longer than the lifetime of the
      quantum-dot transition, and the single photons exhibit a linewidth which is
      inherited from the excitation laser. In contrast, intensity-correlation
      measurements reveal that this photon source maintains a high degree of
      antibunching behavior on the order of the transition lifetime with vanishing two
      photon scattering probability. Generating decoherence-free phase-locked single
      photons from multiple quantum systems will be feasible with our approach.

PMID- 22463635
TI  - Photon production from the vacuum close to the superradiant transition: linking
      the dynamical Casimir effect to the Kibble-Zurek mechanism.
AB  - The dynamical Casimir effect (DCE) predicts the generation of photons from the
      vacuum due to the parametric amplification of the quantum fluctuations of an
      electromagnetic field. The verification of such an effect is still elusive in
      optical systems due to the very demanding requirements of its experimental
      implementation. We show that an ensemble of two-level atoms collectively coupled
      to the electromagnetic field of a cavity, driven at low frequencies and close to
      a quantum phase transition, stimulates the production of photons from the vacuum.
      This paves the way to an effective simulation of the DCE through a mechanism that
      has recently found experimental demonstration. The spectral properties of the
      emitted radiation reflect the critical nature of the system and allow us to link
      the detection of the DCE to the Kibble-Zurek mechanism for the production of
      defects when crossing a continuous phase transition.

PMID- 22463636
TI  - Ultrafast photon-photon interaction in a strongly coupled quantum dot-cavity
      system.
AB  - We study dynamics of the interaction between two weak light beams mediated by a
      strongly coupled quantum dot-photonic crystal cavity system. First, we perform
      all-optical switching of a weak continuous-wave signal with a pulsed control
      beam, and then perform switching between two weak pulsed beams (40 ps pulses).
      Our results show that the quantum dot-nanocavity system enables fast,
      controllable optical switching at the single-photon level.

PMID- 22463637
TI  - Subwavelength modulational instability and plasmon oscillons in nanoparticle
      arrays.
AB  - We study modulational instability in nonlinear arrays of subwavelength metallic
      nanoparticles and analyze numerically nonlinear scenarios of the instability
      development. We demonstrate that modulational instability can lead to the
      formation of regular periodic or quasiperiodic modulations of the polarization.
      We reveal that such nonlinear nanoparticle arrays can support long-lived standing
      and moving oscillating nonlinear localized modes--plasmon oscillons.

PMID- 22463638
TI  - Four-wave mixing from Fe3+ spins in sapphire.
AB  - Fe(3+) ions in sapphire exhibit an electron spin resonance which interacts
      strongly with high-Q whispering gallery modes at microwave frequencies. We report
      the first observation of a third-order paramagnetic nonlinear susceptibility in
      such a resonator at cryogenic temperatures and the first demonstration of four
      wave mixing using this parametric nonlinearity. This observation of an all
      microwave nonlinearity is an enabling step towards a host of quantum measurement
      and control applications which utilize spins in solids.

PMID- 22463639
TI  - Optomechanical self-channeling of light in a suspended planar dual-nanoweb
      waveguide.
AB  - It is shown that optomechanical forces can cause nonlinear self-channeling of
      light in a planar dual-slab waveguide. A system of two parallel silica nanowebs,
      spaced ~100 nm and supported inside a fiber capillary, is studied theoretically
      and an iterative scheme developed to analyze its nonlinear optomechanical
      properties. Steady-state field distributions and mechanical deformation profiles
      are obtained, demonstrating that self-channeling is possible in realistic
      structures at launched powers as low as a few mW. The differential optical
      nonlinearity of the self-channeled mode can be as much as 10*10(6) times higher
      than the corresponding electronic Kerr nonlinearity. It is also intrinsically
      broadband, does not utilize resonant effects, can be viewed as a consequence of
      the extreme nonlocality of the mechanical response, and in fact is a notable
      example of a so-called accessible soliton.

PMID- 22463641
TI  - Chaos and statistical relaxation in quantum systems of interacting particles.
AB  - We study the transition to chaos and the emergence of statistical relaxation in
      isolated dynamical quantum systems of interacting particles. Our approach is
      based on the concept of delocalization of the eigenstates in the energy shell,
      controlled by the Gaussian form of the strength function. We show that, although
      the fluctuations of the energy levels in integrable and nonintegrable systems are
      different, the global properties of the eigenstates are quite similar, provided
      the interaction between particles exceeds some critical value. In this case, the
      statistical relaxation of the systems is comparable, irrespective of whether or
      not they are integrable. The numerical data for the quench dynamics manifest
      excellent agreement with analytical predictions of the theory developed for
      systems of two-body interactions with a completely random character.

PMID- 22463640
TI  - Spontaneous formation of synchronization clusters in homogenous neuronal
      ensembles induced by noise and interaction delays.
AB  - The spontaneous formation of clusters of synchronized spiking in a structureless
      ensemble of equal stochastically perturbed excitable neurons with delayed
      coupling is demonstrated for the first time. The effect is a consequence of a
      subtle interplay between interaction delays, noise, and the excitable character
      of a single neuron. The dependence of the cluster properties on the time lag,
      noise intensity, and the synaptic strength is investigated.

PMID- 22463642
TI  - Capillary pressure and contact line force on a soft solid.
AB  - The surface free energy, or surface tension, of a liquid interface gives rise to
      a pressure jump when the interface is curved. Here we show that a similar
      capillary pressure arises at the interface of soft solids. We present
      experimental evidence that immersion of a thin elastomeric wire into a liquid
      induces a substantial elastic compression due to the solid capillary pressure at
      the bottom. We quantitatively determine the effective surface tension from the
      elastic displacement field and find a value comparable to the liquid-vapor
      surface tension. Most importantly, these results also reveal the way the liquid
      pulls on the solid close to the contact line: the capillary force is not oriented
      along the liquid-air interface, nor perpendicularly to the solid surface, as
      previously hypothesized, but towards the interior of the liquid.

PMID- 22463643
TI  - Turbulent pipe flow at extreme Reynolds numbers.
AB  - Both the inherent intractability and complex beauty of turbulence reside in its
      large range of physical and temporal scales. This range of scales is captured by
      the Reynolds number, which in nature and in many engineering applications can be
      as large as 10(5)-10(6). Here, we report turbulence measurements over an
      unprecedented range of Reynolds numbers using a unique combination of a high
      pressure air facility and a new nanoscale anemometry probe. The results reveal
      previously unknown universal scaling behavior for the turbulent velocity
      fluctuations, which is remarkably similar to the well-known scaling behavior of
      the mean velocity distribution.

PMID- 22463644
TI  - Long-range persistence of femtosecond modulations on laser-plasma-accelerated
      electron beams.
AB  - Laser plasma accelerators have produced femtosecond electron bunches with a
      relative energy spread ranging from 100% to a few percent. Simulations indicate
      that the measured energy spread can be dominated by a correlated spread, with the
      slice spread significantly lower. Measurements of coherent optical transition
      radiation are presented for broad-energy-spread beams with laser-induced density
      and momentum modulations. The long-range (meter-scale) observation of coherent
      optical transition radiation indicates that the slice energy spread is below the
      percent level to preserve the modulations.

PMID- 22463645
TI  - Scaling of spontaneous rotation with temperature and plasma current in tokamaks.
AB  - Using theoretical arguments, a simple scaling law for the size of the intrinsic
      rotation observed in tokamaks in the absence of a momentum injection is found:
      The velocity generated in the core of a tokamak must be proportional to the ion
      temperature difference in the core divided by the plasma current, independent of
      the size of the device. The constant of proportionality is of the order of 10
      km.s(-1).MA.keV(-1). When the intrinsic rotation profile is hollow, i.e., it is
      countercurrent in the core of the tokamak and cocurrent in the edge, the scaling
      law presented in this Letter fits the data remarkably well for several tokamaks
      of vastly different size and heated by different mechanisms.

PMID- 22463646
TI  - Understanding the low-frequency quasilocalized modes in disordered colloidal
      systems.
AB  - In disordered colloidal systems, we experimentally measure the normal modes with
      the covariance matrix method and clarify the origin of low-frequency
      quasilocalization at the single-particle level. We observe important features
      from both jamming and glass simulations: There is a plateau in the density of
      states [D(omega)] which is suppressed upon compression, as predicted by jamming;
      within the same systems, we also find that the low-frequency quasilocalization
      originates from the large vibrations of defective structures coupled with
      transverse excitations, consistent with a recent glass simulation. The
      coexistence of these features demonstrates an experimental link between jamming
      and glass. Extensive simulations further show that such a structural origin of
      quasilocalization is universally valid for various temperatures and volume
      fractions.

PMID- 22463647
TI  - Exceptionally low shear modulus in a prototypical imidazole-based metal-organic
      framework.
AB  - Using Brillouin scattering, we measured the single-crystal elastic constants
      (C(ij)'s) of a prototypical metal-organic framework (MOF): zeolitic imidazolate
      framework (ZIF)-8 [Zn(2-methylimidazolate)(2)], which adopts a zeolitic sodalite
      topology and exhibits large porosity. Its C(ij)'s under ambient conditions are
      (in GPa) C(11)=9.522(7), C(12)=6.865(14), and C(44)=0.967(4). Tensorial analysis
      of the C(ij)'s reveals the complete picture of the anisotropic elasticity in
      cubic ZIF-8. We show that ZIF-8 has a remarkably low shear modulus G(min) < or
      approximately 1 GPa, which is the lowest yet reported for a single-crystalline
      extended solid. Using ab initio calculations, we demonstrate that ZIF-8's C(ij)'s
      can be reliably predicted, and its elastic deformation mechanism is linked to the
      pliant ZnN(4) tetrahedra. Our results shed new light on the role of elastic
      constants in establishing the structural stability of MOF materials and thus
      their suitability for practical applications.

PMID- 22463648
TI  - Experimental test of universality of the Anderson transition.
AB  - We experimentally test the universality of the Anderson three dimensional metal
      insulator transition, using a quasiperiodic atomic kicked rotor. Nine sets of
      parameters controlling the microscopic details have been tested. Our observation
      indicates that the transition is of second order, with a critical exponent
      independent of the microscopic details; the average value 1.63+/-0.05 agrees very
      well with the numerically predicted value nu=1.58.

PMID- 22463649
TI  - Ab initio nonequilibrium molecular dynamics in the solid superionic conductor
      LiBH4.
AB  - The color-diffusion algorithm is applied to ab initio molecular dynamics
      simulation of hexagonal LiBH(4) to determine the lithium diffusion coefficient
      and diffusion mechanisms. Even in the best solid lithium ion conductors, the time
      scale of ion diffusion is too long to be readily accessible by ab initio
      molecular dynamics at a reasonable computational cost. In our nonequilibrium
      method, rare events are accelerated by the application of an artificial external
      field acting on the mobile species; the system response to this perturbation is
      accurately described in the framework of linear response theory and is directly
      related to the diffusion coefficient, thus resulting in a controllable
      approximation. The calculated lithium ionic conductivity of LiBH(4) closely
      matches published measurements, and the diffusion mechanism can be elucidated
      directly from the generated trajectory.

PMID- 22463650
TI  - Competition between electron and phonon excitations in the scattering of nitrogen
      atoms and molecules off tungsten and silver metal surfaces.
AB  - We investigate the role played by electron-hole pair and phonon excitations in
      the interaction of reactive gas molecules and atoms with metal surfaces. We
      present a theoretical framework that allows us to evaluate within a full
      dimensional dynamics the combined contribution of both excitation mechanisms
      while the gas particle-surface interaction is described by an ab initio potential
      energy surface. The model is applied to study energy dissipation in the
      scattering of N(2) on W(110) and N on Ag(111). Our results show that phonon
      excitation is the dominant energy loss channel, whereas electron-hole pair
      excitations represent a minor contribution. We substantiate that, even when the
      energy dissipated is quantitatively significant, important aspects of the
      scattering dynamics are well captured by the adiabatic approximation.

PMID- 22463651
TI  - Large reaction rate enhancement in formation of ultrathin AuSi eutectic layers.
AB  - Metal-semiconductor eutectic liquids play a key role in both the fundamental
      understanding of atomic interactions and nanoscale synthesis and catalysis. At
      reduced sizes they exhibit properties distinct from the bulk. In this work we
      show an unusual effect that the formation of AuSi eutectic liquid layers is much
      easier for smaller thicknesses. The alloying reaction rate is enhanced by over 20
      times when the thickness is reduced from 300 to 20 nm. The strong enhancement is
      attributed to a strain-induced increase in the chemical potential of the solid
      layer prior to the alloying reaction.

PMID- 22463652
TI  - Hidden multiple-spin interactions as an origin of spin scalar chiral order in
      frustrated Kondo lattice models.
AB  - We reveal the significance of kinetic-driven multiple-spin interactions hidden in
      geometrically frustrated Kondo lattice models. Carefully examining the
      perturbation in terms of the spin-charge coupling up to the fourth order, we find
      that a positive biquadratic interaction is critically enhanced and plays a
      crucial role on stabilizing a spin scalar chiral order near 1/4 filling in a
      triangular lattice case. This is a generalized Kohn anomaly, appearing only when
      the second-order perturbation is inefficient because of the degeneracy under
      frustration. The mechanism is potentially common to frustrated spin-charge
      coupled systems, leading to emergence of unusual magnetic orders.

PMID- 22463653
TI  - Tuning the magnetic dimensionality by charge ordering in the molecular TMTTF
      salts.
AB  - We theoretically investigate the interplay between charge ordering and magnetic
      states in quasi-one-dimensional molecular conductors TMTTF(2)X, motivated by the
      observation of a complex variation of competing and/or coexisting phases. We show
      that the ferroelectric-type charge order increases two-dimensional
      antiferromagnetic spin correlation, whereas in the one-dimensional regime two
      different spin-Peierls states are stabilized. By using first-principles band
      calculations for the estimation for the transfer integrals and comparing our
      results with the experiments, we identify the controlling parameters in the
      experimental phase diagram to be not only the interchain transfer integrals but
      also the amplitude of the charge order.

PMID- 22463654
TI  - Chirality waves in two-dimensional magnets.
AB  - We theoretically show that moderate interaction between electrons confined to
      move in a plane and localized magnetic moments leads to formation of a
      noncoplanar magnetic state. The state is similar to the Skyrmion crystal recently
      observed in cubic systems with the Dzyaloshinskii-Moriya interaction; however, it
      does not require spin-orbit interaction. The noncoplanar magnetism is accompanied
      by the ground-state electrical and spin currents, generated via the real-space
      Berry phase mechanism. We examine the stability of the state with respect to
      lattice discreteness effects and the magnitude of magnetic exchange interaction.
      The state can be realized in a number of transition metal and magnetic
      semiconductor systems.

PMID- 22463655
TI  - Fragility of surface states and robustness of topological order in Bi2Se3 against
      oxidation.
AB  - Topological surface states are protected against local perturbations, but this
      protection does not extend to chemical reaction over the whole surface, as
      demonstrated by theoretical studies of the oxidation of Bi(2)Se(3) and its
      effects on the surface spin polarization and current. While chemisorption of O(2)
      largely preserves the topological surface states, reaction with atomic O removes
      the original surface states and yields two new sets of surface states. One set
      forms a regular Dirac cone but is topologically trivial. The other set, while
      topologically relevant, forms an unusual rounded Dirac cone. The details are
      governed by the hybridization interaction at the interface.

PMID- 22463626
TI  - Particle-yield modification in jetlike azimuthal dihadron correlations in Pb-Pb
      collisions at ?s(NN)=2.76 TeV.
AB  - The yield of charged particles associated with high-p(t) trigger particles
      (8<p(t)<15 GeV/c) is measured with the ALICE detector in Pb-Pb collisions at
      ?s(NN)=2.76 TeV relative to proton-proton collisions at the same energy. The
      conditional per-trigger yields are extracted from the narrow jetlike correlation
      peaks in azimuthal dihadron correlations. In the 5% most central collisions, we
      observe that the yield of associated charged particles with transverse momenta
      p(t)>3 GeV/c on the away side drops to about 60% of that observed in pp
      collisions, while on the near side a moderate enhancement of 20%-30% is found.

PMID- 22463656
TI  - Deformation and scattering in graphene over substrate steps.
AB  - The electrical properties of graphene depend sensitively on the substrate. For
      example, recent measurements of epitaxial graphene on SiC show resistance arising
      from steps on the substrate. Here we calculate the deformation of graphene at
      substrate steps, and the resulting electrical resistance, over a wide range of
      step heights. The elastic deformations contribute only a very small resistance at
      the step. However, for graphene on SiC(0001) there is strong substrate-induced
      doping, and this is substantially reduced on the lower side of the step where
      graphene pulls away from the substrate. The resulting resistance explains the
      experimental measurements.

PMID- 22463657
TI  - Scanning-tunneling microscope imaging of single-electron solitons in a material
      with incommensurate charge-density waves.
AB  - We report on scanning-tunneling microscopy experiments in a charge-density wave
      (CDW) system allowing visually capturing and studying in detail the individual
      solitons corresponding to the self-trapping of just one electron. This "Amplitude
      Soliton" is marked by vanishing of the CDW amplitude and by the pi shift of its
      phase. It might be the realization of the spinon--the long-sought particle (along
      with the holon) in the study of science of strongly correlated electronic
      systems. As a distinct feature we also observe one-dimensional Friedel
      oscillations superimposed on the CDW which develop independently of solitons.

PMID- 22463658
TI  - Spin and Majorana polarization in topological superconducting wires.
AB  - We study a one-dimensional wire with strong Rashba and Dresselhaus spin-orbit
      coupling (SOC), which supports Majorana fermions when subject to a Zeeman
      magnetic field and in the proximity of a superconductor. Using both analytical
      and numerical techniques we calculate the electronic spin texture of the Majorana
      end states. We find that the spin polarization of these states depends on the
      relative magnitude of the Rashba and Dresselhaus SOC components. Moreover, we
      define and calculate a local "Majorana polarization" and "Majorana density" and
      argue that they can be used as order parameters to characterize the topological
      transition between the trivial system and the system exhibiting Majorana bound
      modes. We find that the local Majorana polarization is correlated to the
      transverse spin polarization, and we propose to test the presence of Majorana
      fermions in a 1D system by a spin-polarized density of states measurement.

PMID- 22463659
TI  - Single-charge transistor based on the charge-phase duality of a superconducting
      nanowire circuit.
AB  - We propose a transistorlike circuit including two serially connected segments of
      a narrow superconducting nanowire joint by a wider segment with a capacitively
      coupled gate in between. This circuit is made of amorphous NbSi film and embedded
      in a network of on-chip Cr microresistors ensuring a sufficiently high external
      electromagnetic impedance. Assuming a virtual regime of quantum phase slips (QPS)
      in two narrow segments of the wire, leading to quantum interference of voltages
      on these segments, this circuit is dual to the dc SQUID. Our samples demonstrated
      appreciable Coulomb blockade voltage (analog of critical current of the SQUIDs)
      and periodic modulation of this blockade by an electrostatic gate (analog of flux
      modulation in the SQUIDs). The model of this QPS transistor is discussed.

PMID- 22463660
TI  - Ultrafast momentum-dependent response of electrons in antiferromagnetic EuFe2As2
      driven by optical excitation.
AB  - Employing the momentum sensitivity of time- and angle-resolved photoemission
      spectroscopy we demonstrate the analysis of ultrafast single- and many-particle
      dynamics in antiferromagnetic EuFe(2)As(2). Their separation is based on a
      temperature-dependent difference of photoexcited hole and electron relaxation
      times probing the single-particle band and the spin density wave gap,
      respectively. Reformation of the magnetic order occurs at 800 fs, which is 4
      times slower compared to electron-phonon equilibration due to a smaller spin
      dependent relaxation phase space.

PMID- 22463661
TI  - Distribution of supercurrent switching in graphene under the proximity effect.
AB  - We study the stochastic nature of switching current in hysteretic current-voltage
      characteristics of superconductor-graphene-superconductor junctions. We find that
      the dispersion of the switching current distribution scales with temperature as
      sigma(I) proportional to T(alpha(G)) with alpha(G) as low as 1/3. This
      observation is in sharp contrast to the known Josephson junction behavior where
      sigma(I) proportional to T(alpha(J)) with alpha(J)=2/3. We propose an explanation
      using a generalized version of Kurkijarvi's theory for the flux stability in rf
      SQUID and attribute this anomalous effect to the temperature dependence of the
      critical current which persists down to low temperatures.

PMID- 22463662
TI  - Theoretical description of the superconducting state of nanostructures at
      intermediate temperatures: a combined treatment of collective modes and
      fluctuations.
AB  - A rigorous treatment of the combined effect of thermal and quantum fluctuations
      in a zero-dimensional superconductor is considered one of the most relevant and
      still-unsolved problems in the theory of nanoscale superconductors. In this
      Letter, we notice that the divergences that plagued previous calculations are
      avoided by identifying and treating nonperturbatively a low-energy collective
      mode. In this way, we obtain for the first time closed expressions for the
      partition function and the superconducting order parameter which include both
      types of fluctuation and are valid at any temperature and to leading order in
      delta/Delta(0), where delta is the mean level spacing and Delta(0) is the bulk
      energy gap. Our results pave the way for a quantitative description of
      superconductivity in nanostructures at finite temperature and pairing in hot
      nuclei.

PMID- 22463663
TI  - Wilson ratio of a Tomonaga-Luttinger liquid in a spin-1/2 Heisenberg ladder.
AB  - Using micromechanical force magnetometry, we have measured the magnetization of
      the strong-leg spin-1/2 ladder compound (C(7)H(10)N)(2)CuBr(2) at temperatures
      down to 45 mK. Low-temperature magnetic susceptibility as a function of field
      exhibits a maximum near the critical field H(c) at which the magnon gap vanishes,
      as expected for a gapped one-dimensional antiferromagnet. Above H(c) a clear
      minimum appears in the magnetization as a function of temperature, as predicted
      by theory. In this field region, the susceptibility in conjunction with our
      specific-heat data yields the Wilson ratio R(W). The result supports the relation
      R(W)=4K, where K is the Tomonaga-Luttinger-liquid parameter.

PMID- 22463664
TI  - Multiferroic behavior in trimerized Mott insulators.
AB  - We demonstrate multiferroic behavior in trimerized Mott insulators through the
      interplay between spins and electric dipole moments resulting from electronic
      charge fluctuations in frustrated units. The model consists of stacked triangular
      layers of trimers with small intertrimer exchange interactions J' and J''.
      Ferroelectric states coexist with ferro- or antiferromagnetic orderings depending
      on the value of the magnetic field H and the sign of the interlayer exchange J''.
      The electric polarization undergoes abrupt changes as a function of H.

PMID- 22463665
TI  - Ferroelectric soft mode in a SrTiO3 thin film impulsively driven to the
      anharmonic regime using intense picosecond terahertz pulses.
AB  - The ferroelectric soft mode in a SrTiO(3) thin film was impulsively driven to a
      large amplitude using intense picosecond terahertz pulses. As the terahertz
      electric field increased, the soft-mode absorption peak exhibited blueshifting
      and spectral narrowing. A classical anharmonic oscillator model suggests that the
      induced displacement is comparable to that of the ferroelectric phase transition.
      The spectral narrowing indicates that the displacement exceeds that induced by
      any inhomogeneities in the film, demonstrating that the method can be used to
      explore intrinsic quartic anharmonicity.

PMID- 22463666
TI  - Realizing optical magnetism from dielectric metamaterials.
AB  - We demonstrate, for the first time, an all-dielectric metamaterial composite in
      the midinfrared based on micron-sized, high-index tellurium dielectric
      resonators. Dielectric resonators are desirable compared to conventional
      metallodielectric metamaterials at optical frequencies as they are largely
      angular invariant, free of Ohmic loss, and easily integrated into three
      dimensional volumes. Measurements and simulation provide evidence of optical
      magnetism, which could be used for infrared magnetic mirrors, hard or soft
      surfaces, and subwavelength cavities.

PMID- 22463667
TI  - Thermoelectrically pumped light-emitting diodes operating above unity efficiency.
AB  - A heated semiconductor light-emitting diode at low forward bias voltage V<k(B)T/q
      is shown to use electrical work to pump heat from the lattice to the photon
      field. Here the rates of both radiative and nonradiative recombination have
      contributions at linear order in V. As a result the device's wall-plug (i.e.,
      power conversion) efficiency is inversely proportional to its output power and
      diverges as V approaches zero. Experiments directly confirm for the first time
      that this behavior continues beyond the conventional limit of unity electrical-to
      optical power conversion efficiency.

PMID- 22463668
TI  - Coherent storage of photoexcited triplet states using 29Si nuclear spins in
      silicon.
AB  - Pulsed electron paramagnetic resonance spectroscopy of the photoexcited,
      metastable triplet state of the oxygen-vacancy center in silicon reveals that the
      lifetime of the m(s)=+/-1 sublevels differs significantly from that of the m(s)=0
      state. We exploit this significant difference in decay rates to the ground
      singlet state to achieve nearly ~100% electron-spin polarization within the
      triplet. We further demonstrate the transfer of a coherent state of the triplet
      electron spin to, and from, a hyperfine-coupled, nearest-neighbor (29)Si nuclear
      spin. We measure the coherence time of the (29)Si nuclear spin employed in this
      operation and find it to be unaffected by the presence of the triplet electron
      spin and equal to the bulk value measured by nuclear magnetic resonance.

PMID- 22463669
TI  - Twist neutrality and the diameter of the nucleosome core particle.
AB  - The diameter of the nucleosome core particle is the same for all the eukaryotes.
      Here we discuss the possibility that this selectiveness is consistent with a
      propensity for twist neutrality, in particular, for the double helical DNA to
      stay rotationally neutral when strained. Reorganization of DNA cannot be done
      without some level of temporal tensile stress, and as a consequence chiral
      molecules, such as helices, will twist under strain. The requirement that the
      nucleosome, constituting the nucleosome core particle and linker DNA, has a
      vanishing strain-twist coupling leads to a requirement for the amount of bending.
      For the diameter of the coiled DNA we obtain the relatively accurate numerical
      estimate of 2R=82 A.

PMID- 22463670
TI  - Collective motion and nonequilibrium cluster formation in colonies of gliding
      bacteria.
AB  - We characterize cell motion in experiments and show that the transition to
      collective motion in colonies of gliding bacterial cells confined to a monolayer
      appears through the organization of cells into larger moving clusters. Collective
      motion by nonequilibrium cluster formation is detected for a critical cell
      packing fraction around 17%. This transition is characterized by a scale-free
      power-law cluster-size distribution, with an exponent 0.88+/-0.07, and the
      appearance of giant number fluctuations. Our findings are in quantitative
      agreement with simulations of self-propelled rods. This suggests that the
      interplay of self-propulsion and the rod shape of bacteria is sufficient to
      induce collective motion.

PMID- 22463672
TI  - Heterogeneous shear in hard sphere glasses.
AB  - There is growing evidence that the flow of driven amorphous solids is not
      homogeneous, even if the macroscopic stress is constant across the system. Via
      event-driven molecular dynamics simulations of a hard sphere glass, we provide
      the first direct evidence for a correlation between the fluctuations of the local
      volume fraction and the fluctuations of the local shear rate. Higher shear rates
      do preferentially occur at regions of lower density and vice versa. The temporal
      behavior of fluctuations is governed by a characteristic time scale, which, when
      measured in units of strain, is independent of shear rate in the investigated
      range. Interestingly, the correlation volume is also roughly constant for the
      same range of shear rates. A possible connection between these two observations
      is discussed.

PMID- 22463671
TI  - Spatiotemporal dynamics of bumblebees foraging under predation risk.
AB  - We analyze 3D flight paths of bumblebees searching for nectar in a laboratory
      experiment with and without predation risk from artificial spiders. For the
      flight velocities we find mixed probability distributions reflecting the access
      to the food sources while the threat posed by the spiders shows up only in the
      velocity correlations. The bumblebees thus adjust their flight patterns spatially
      to the environment and temporally to predation risk. Key information on response
      to environmental changes is contained in temporal correlation functions, as we
      explain by a simple emergent model.

PMID- 22463673
TI  - Noisy optical pulses enhance the temporal resolution of pump-probe spectroscopy.
AB  - Time-resolved measurements of quantum dynamics are based on the availability of
      controlled events that are shorter than the typical evolution time scale of the
      processes to be observed. Here we introduce the concept of noise-enhanced pump
      probe spectroscopy, allowing the measurement of dynamics significantly shorter
      than the average pulse duration by exploiting randomly varying, partially
      coherent light fields consisting of bunched colored noise. These fields are shown
      to be superior by more than a factor of 10 to frequency-stabilized fields, with
      important implications for time-resolved experiments at x-ray free-electron
      lasers and, in general, for measurements at the frontiers of temporal resolution
      (e.g., attosecond spectroscopy). As an example application, the concept is used
      to explain the recent experimental observation of vibrational wave-packet motion
      in D(2)(+) on time scales shorter than the average pulse duration.

PMID- 22463674
TI  - Yielding of hard-sphere glasses during start-up shear.
AB  - Concentrated hard-sphere suspensions and glasses are investigated with rheometry,
      confocal microscopy, and Brownian dynamics simulations during start-up shear,
      providing a link between microstructure, dynamics, and rheology. The
      microstructural anisotropy is manifested in the extension axis where the maximum
      of the pair-distribution function exhibits a minimum at the stress overshoot. The
      interplay between Brownian relaxation and shear advection as well as the
      available free volume determine the structural anisotropy and the magnitude of
      the stress overshoot. Shear-induced cage deformation induces local constriction,
      reducing in-cage diffusion. Finally, a superdiffusive response at the steady
      state, with a minimum of the time-dependent effective diffusivity, reflects a
      continuous cage breakup and reformation.

PMID- 22463675
TI  - Expression and characterization of constitutive heat shock protein 70.1 (HSPA-1A)
      gene in in vitro produced and in vivo-derived buffalo (Bubalus bubalis) embryos.
AB  - Cells are blessed with a group of stress protector molecules known as heat shock
      proteins (HSPs), amongst them HSP70, encoded by HSPA-1A gene, is most abundant
      and highly conserved protein. Variety of stresses hampers the developmental
      competence of embryos under in vivo and in vitro conditions. Present work was
      designed to study the quantitative expression of HSPA-1A mRNA in immature oocytes
      (IMO), matured oocytes (MO), in vitro produced (IVP) and in vivo-derived (IVD)
      buffalo embryos to assess the level of stress to which embryos are exposed under
      in vivo and in vitro culture conditions. Further, HSPA-1A gene sequence was
      analysed to determine its homology with other mammalian sequences. The mRNA
      expression analysis was carried out on 72 oocytes (40 IMO; 32 MO), 76 IVP and 55
      IVD buffalo embryos. Expression of HSPA-1A was found in oocytes and throughout
      the developmental stages of embryos examined irrespective of the embryo source;
      however, higher (p < 0.05) expression was observed in 8-16 cell, morula and
      blastocyst stages of IVP embryos as compared to IVD embryos. Phylogenetic
      analysis of bubaline HSPA-1A revealed that it shares 91-98% identity with other
      mammalian sequences. It can be concluded that higher level of HSPA-1A mRNA in IVP
      embryos in comparison with in vivo-derived embryos is an indicator of cellular
      stress in IVP system. This study suggests need for further optimization of in
      vitro culture system in which HSPA-1A gene could be used as a stress biomarker
      during pre-implantation development.

PMID- 22463676
TI  - The association of hypertriglyceridemia with cardiovascular events and
      pancreatitis: a systematic review and meta-analysis.
AB  - BACKGROUND: Hypertriglyceridemia may be associated with important complications.
      The aim of this study is to estimate the magnitude of association and quality of
      supporting evidence linking hypertriglyceridemia to cardiovascular events and
      pancreatitis. METHODS: We conducted a systematic review of multiple electronic
      bibliographic databases and subsequent meta-analysis using a random effects
      model. Studies eligible for this review followed patients longitudinally and
      evaluated quantitatively the association of fasting hypertriglyceridemia with the
      outcomes of interest. Reviewers working independently and in duplicate reviewed
      studies and extracted data. RESULTS: 35 studies provided data sufficient for meta
      analysis. The quality of these observational studies was moderate to low with
      fair level of multivariable adjustments and adequate exposure and outcome
      ascertainment. Fasting hypertriglyceridemia was significantly associated with
      cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31
      2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction
      (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in
      one study only). The association with all-cause mortality was not statistically
      significant. CONCLUSIONS: The current evidence suggests that fasting
      hypertriglyceridemia is associated with increased risk of cardiovascular death,
      MI, cardiovascular events, and possibly acute pancreatitis.Precis:
      hypertriglyceridemia is associated with increased risk of cardiovascular death,
      MI, cardiovascular events, and possibly acute pancreatitis.

PMID- 22463677
TI  - alphaB-crystallin is a useful marker for triple negative and basal breast
      cancers.
AB  - AIMS: Basal-like breast cancers (BLBCs), a breast cancer subtype with triple
      negative status, pose significant problems in clinical management because of
      their aggressive behaviour. Recently, an association between alphaBeta-crystallin
      expression and BLBCs has been suggested, and we therefore investigated whether
      alphaBeta-crystallin could be a putative marker allowing BLBCs to be identified
      more accurately. METHODS AND RESULTS: We evaluated the expression of alphaB
      crystallin and other biomarkers in 395 cases of breast carcinoma by
      immunohistochemistry, analysed the correlation of their expression with different
      breast cancer subtypes, and compared their sensitivity as well as specificity in
      identifying BLBCs. alphaBeta-crystallin expression was found to be correlated
      positively with basal markers and histological subtypes associated with BLBCs. A
      significant positive correlation of alphaBeta-crystallin expression was also
      found with triple-negative breast cancers (TNBC) (C = 0.409, P < 0.001) and BLBCs
      (C = 0.393, P < 0.001). Comparing alphaBeta-crystallin with other basal markers,
      only alphaBeta-crystallin demonstrated both high sensitivity (48.6%) and
      specificity (93.8%) as a TNBC marker. All other markers showed either a lower
      sensitivity of <40% or a lower specificity of <90%. alphaBeta-crystallin also
      demonstrated a high specificity (92.9%) and an even higher sensitivity (56.5%)
      for BLBCs. CONCLUSIONS: The findings indicated that alphaB-crystallin was a
      highly sensitive and specific marker for TNBCs and BLBCs.

PMID- 22463678
TI  - Selection against hybrids in mixed populations of Brassica rapa and Brassica
      napus: model and synthesis.
AB  - Pollen of the crop oilseed rape (Brassica napus, AACC) can cross-fertilize ovules
      of Brassica rapa (AA), which leads to an influx of unpaired C-chromosomes into
      wild B. rapa populations. The presence of such extra chromosomes is thought to be
      an indicator of introgression. Backcrosses and F(1) hybrids were found in Danish
      populations but, surprisingly, only F(1) hybrids were found in the UK and the
      Netherlands. Here, a model tests how the level of selection and biased vs
      unbiased transmission affect the population frequency of C-chromosomes. In the
      biased-transmission scenario the experimental results of the first backcross are
      extrapolated to estimate survival of gametes with different numbers of C
      chromosomes from all crosses in the population. With biased transmission, the
      frequency of C-chromosomes always rapidly declines to zero. With unbiased
      transmission, the continued presence of plants with extra C-chromosomes depends
      on selection in the adult stage and we argue that this is the most realistic
      option for modeling populations. We suggest that selection in the field against
      plants with unpaired C-chromosomes is strong in Dutch and UK populations. The
      model highlights what we do not know and makes suggestions for further research
      on introgression.

PMID- 22463679
TI  - Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic
      minipigs.
AB  - BACKGROUND: Accelerated atherosclerosis is the main cause of late aortocoronary
      vein graft failure. We aimed to develop a large animal model for the study of
      pathogenesis and treatment of vein graft atherosclerosis. METHODS: An autologous
      reversed jugular vein graft was inserted end-to-end into the transected common
      carotid artery of ten hypercholesteroemic minipigs. The vein grafts were
      investigated 12-14 weeks later with ultrasound and angiograpy in vivo and
      microscopy post mortem. RESULTS: One minipig died during follow up (patent vein
      graft at autopsy), and one vein graft thrombosed early. In the remaining eight
      patent vein grafts, the mean (standard deviation) intima-media thickness was 712
      MUm (276 MUm) versus 204 MUm (74 MUm) in the contralateral control internal
      jugular veins (P < .01). Advanced atherosclerotic plaques were found in three of
      four oversized vein grafts (diameter of graft > diameter of artery). No plaques
      were found in four non-oversized vein grafts (P < .05). CONCLUSIONS: Our model of
      jugular vein graft in the common carotid artery of hypercholesterolemic minipigs
      displayed the components of human vein graft disease, i.e. thrombosis, intimal
      hyperplasia, and atherosclerosis. Advanced atherosclerosis, the main cause of
      late failure of human aortocoronary vein grafts was only seen in oversized
      grafts. This finding suggests that oversized vein grafts may have detrimental
      effects on patient outcome.

PMID- 22463680
TI  - In vivo interactions between ionizing radiation, inflammation and chemical
      carcinogens identified by increased DNA damage responses.
AB  - Exposure to ionizing radiation or a variety of chemical agents is known to
      increase the risk of developing malignancy and many tumors have been linked to
      inflammatory processes. In most studies, the potentially harmful effects of
      ionizing radiation or other agents are considered in isolation, mainly due to the
      large number of experiments required to assess the effects of mixed exposures
      with different doses and different schedules, and the length of time and expense
      of studies using disease as the measure of outcome. Here, we have used short-term
      DNA damage responses to identify interactive effects of mixed exposures. The data
      demonstrate that exposure to ionizing radiation on two separate occasions ten
      days apart leads to an increase in the percentage of cells with a sub-G(0) DNA
      content compared to cells exposed only once, and this is a greater than additive
      effect. Short-term measurements of p53 stabilization, induction of p21/Cdkn1a and
      of apoptosis also identify these interactive effects. We also demonstrate similar
      interactive effects of radiation with the mutagenic chemical methyl-nitrosourea
      and with a nonspecific pro-inflammatory agent, lipopolysaccharide. The magnitude
      of the interactive effects is greater in cells taken from mice first exposed as
      juveniles compared to adults. These data indicate that short-term measurements of
      DNA damage and response to damage are useful for the identification of
      interactions between ionizing radiation and other agents.

PMID- 22463681
TI  - The effect of reductant levels on the formation of damage lesions derived from a
      2-deoxyribose radical in ssDNA.
AB  - Thiols play a major role in the outcome of oxidative damage to DNA when it is
      initiated through cellular exposure to ionizing radiation. DNA radicals formed
      under aerobic conditions are converted to peroxyl radicals through trapping by
      oxygen at a diffusion-controlled rate. As a primary source of cellular reductant,
      thiols are responsible for the conversion of these DNA-derived peroxyl radicals
      to their corresponding hydrogen peroxides and subsequent strand breaks. Through
      the use of modified nucleotides, which act as precursors to nucleic acid
      radicals, we have investigated the effect of varying amounts of the cellular
      thiol glutathione (GSH) on the distribution of damage products produced from a 2
      deoxyribose radical in DNA: the C3'-thymidinyl radical. The C3'-thymidinyl
      radical results from the abstraction of a hydrogen atom from the C3'-position of
      DNA oligomers at a thymidine residue, and is known to deliver several DNA damage
      lesions including the 3'-phosphoglycolaldehyde, 3'-phosphoglycolate and a 5'
      aldehyde. Here we show that the level of GSH present has an impact on the level
      of production of these C3'-thymidinyl radical derived damage products.

PMID- 22463682
TI  - Towards automatic measurement of anteversion and neck-shaft angles in human
      femurs using CT images.
AB  - Automatic assessment of human femur morphology may provide useful clinical
      information with regard to hip and knee surgery, prosthesis design and management
      of hip instability. To this end, neck-shaft and anteversion angles are usually
      used. We propose a full automatic method to estimate these angles in human
      femurs. Multislice CT images from 18 dried bones were analysed. The algorithm
      fits 3D cylinders to different regions of the bone to estimate the angles. A
      manual segmentation and a conventional angle assessment were used for validation.
      We found anteversion angle as 20 +/- 7 degrees  and neck-shaft angle as 130 +/- 9
      degrees . Mean distances from femur surface to cylinders were 5.5 +/- 0.6, 3.5 +/
      0.6 and 2.4 +/- 0.4 mm for condyles, diaphysis and neck regions, respectively.
      Automatic and conventional angles were positively correlated (r(2)>0.85). Manual
      and automatic segmentations did not differ. The method was fast and 100%
      reproducible. A robust in vivo segmentation algorithm should be integrated to
      advance towards a clinically compliant methodology.

PMID- 22463683
TI  - Could gender equality in parental leave harm off-springs' mental health? A
      registry study of the Swedish parental/child cohort of 1988/89.
AB  - INTRODUCTION: Mental ill-health among children and young adults is a growing
      public health problem and research into causes involves consideration of family
      life and gender practice. This study aimed at exploring the association between
      parents' degree of gender equality in childcare and children's mental ill-health.
      METHODS: The population consisted of Swedish parents and their firstborn child in
      1988-1989 (N = 118 595 family units) and the statistical method was multiple
      logistic regression. Gender equality of childcare was indicated by the division
      of parental leave (1988-1990), and child mental ill-health was indicated by
      outpatient mental care (2001-2006) and drug prescription (2005-2008), for anxiety
      and depression. RESULTS: The overall finding was that boys with gender
      traditional parents (mother dominance in childcare) have lower risk of depression
      measured by outpatient mental care than boys with gender-equal parents, while
      girls with gender traditional and gender untraditional parents (father dominance
      in childcare) have lower risk of anxiety measured by drug prescription than girls
      with gender-equal parents. CONCLUSIONS: This study suggests that unequal
      parenting regarding early childcare, whether traditional or untraditional, is
      more beneficial for offspring's mental health than equal parenting. However,
      further research is required to confirm our findings and to explore the pathways
      through which increased gender equality may influence child health.

PMID- 22463684
TI  - Sensory evaluation of sodium chloride-containing water-in-oil emulsions.
AB  - The sensory perception of water-in-oil emulsions containing a saline-dispersed
      aqueous phase was investigated. Manipulating saltiness perception was achieved by
      varying the mass fraction aqueous phase (MFAP), initial salt load, and surfactant
      concentration [(polyglycerol polyricinoleate (PgPr)] of the emulsions, with
      formulations based on a central composite design. Saltiness and emulsion
      thickness were evaluated using a trained sensory panel, and collected data were
      analyzed using response surface analysis. Emulsion MFAP was the most important
      factor correlated with increased salt taste intensity. Emulsifier concentration
      and interactions between NaCl and PgPr had only minor effects. Emulsions more
      prone to destabilization were perceived as saltier irrespective of their initial
      salt load. The knowledge gained from this study provides a powerful tool for the
      development of novel sodium-reduced liquid-processed foods.

PMID- 22463685
TI  - Synthesis of water-soluble phosphine oxides by Pd/C-catalyzed P-C coupling in
      water.
AB  - Cross-coupling between diphenylphosphine oxide and halogenated benzoic acids
      catalyzed by Pd/C in water is a green, simple, and fast protocol to obtain water
      soluble tertiary phosphine oxides without the addition of ligands and additives.
      Low reaction times and microwave irradiation make this method general and
      excellent for laboratory and large-scale synthesis without the need to use
      organic solvents in reactions and workup.

PMID- 22463686
TI  - Enhanced strain in functional nanoporous gold with a dual microscopic length
      scale structure.
AB  - We have synthesized nanoporous Au with a dual microscopic length scale by
      exploiting the crystal structure of the alloy precursor. The synthesized
      mesoscopic material is characterized by stacked Au layers of submicrometer
      thickness. In addition, each layer displays nanoporosity through the entire bulk.
      It is shown that the thickness of these layers can be tailored via the grain size
      of the alloy precursor. The two-length-scale structure enhances the functional
      properties of nanoporous gold, leading to charge-induced strains of amplitude up
      to 6%, which are roughly 2 orders of magnitude larger than in nanoporous Au with
      the standard one-length-scale porous morphology. A model is presented to describe
      these phenomena.

PMID- 22463687
TI  - A synthetic biology approach to self-regulatory recombinant protein production in
      Escherichia coli.
AB  - BACKGROUND: Recombinant protein production is a process of great industrial
      interest, with products that range from pharmaceuticals to biofuels. Since high
      level production of recombinant protein imposes significant stress in the host
      organism, several methods have been developed over the years to optimize protein
      production. So far, these trial-and-error techniques have proved laborious and
      sensitive to process parameters, while there has been no attempt to address the
      problem by applying Synthetic Biology principles and methods, such as integration
      of standardized parts in novel synthetic circuits. RESULTS: We present a novel
      self-regulatory protein production system that couples the control of recombinant
      protein production with a stress-induced, negative feedback mechanism. The
      synthetic circuit allows the down-regulation of recombinant protein expression
      through a stress-induced promoter. We used E. coli as the host organism, since it
      is widely used in recombinant processes. Our results show that the introduction
      of the self-regulatory circuit increases the soluble/insoluble ratio of
      recombinant protein at the expense of total protein yield. To further elucidate
      the dynamics of the system, we developed a computational model that is in
      agreement with the observed experimental data, and provides insight on the
      interplay between protein solubility and yield. CONCLUSION: Our work introduces
      the idea of a self-regulatory circuit for recombinant protein products, and paves
      the way for processes with reduced external control or monitoring needs. It
      demonstrates that the library of standard biological parts serves as a valuable
      resource for initial synthetic blocks that needs to be further refined to be
      successfully applied in practical problems of biotechnological significance.
      Finally, the development of a predictive model in conjunction with experimental
      validation facilitates a better understanding of the underlying dynamics and can
      be used as a guide to experimental design.

PMID- 22463688
TI  - Acute-onset multifocal motor neuropathy (AMMN): how we meet the diagnosis.
AB  - Multifocal motor neuropathy (MMN) usually progresses insidiously with lower motor
      neuron-type weakness, minimal or no sensory symptoms. Diagnostic criteria include
      motor conduction block (CB) at sites not exposed to compression or entrapment.
      CBs may persist or reverse irrespective of clinical outcome. Acute onset with
      generalized weakness is uncommon. We report four patients who presented acutely
      areflexia, pure motor deficits without sensory disturbances, multifocal CBs
      persisting at the same motor nerves on serial electrophysiological studies. Three
      patients had preceding infections; two showed IgM reactivity against the
      ganglioside GM1. Intravenous immuneglobulin (IVIg) improved or stabilized
      symptoms. Patients 2,3,4 receive maintenance therapy with IVIg for years. Acute
      onset MMN (AMMN) should be differentiated from other immune-mediated neuropathies
      such as acute inflammatory polyneuropathy either demyelinating (AIDP) or axonal
      (AMAN), acute motor conduction block neuropathy (AMCBN), acute-onset chronic
      inflammatory demyelinating polyneuropathy (CIDP). The correct diagnosis deserves
      implications for patient long-term treatment and prognosis. Moreover, the authors
      address the problem of defining the spectrum of MMN particularly in the acute
      setting.

PMID- 22463689
TI  - Replacing conventional carbon nucleophiles with electrophiles: nickel-catalyzed
      reductive alkylation of aryl bromides and chlorides.
AB  - A general method is presented for the synthesis of alkylated arenes by the
      chemoselective combination of two electrophilic carbons. Under the optimized
      conditions, a variety of aryl and vinyl bromides are reductively coupled with
      alkyl bromides in high yields. Under similar conditions, activated aryl chlorides
      can also be coupled with bromoalkanes. The protocols are highly functional-group
      tolerant (-OH, -NHTs, -OAc, -OTs, -OTf, -COMe, -NHBoc, -NHCbz, -CN, -SO(2)Me),
      and the reactions are assembled on the benchtop with no special precautions to
      exclude air or moisture. The reaction displays different chemoselectivity than
      conventional cross-coupling reactions, such as the Suzuki-Miyaura, Stille, and
      Hiyama-Denmark reactions. Substrates bearing both an electrophilic and
      nucleophilic carbon result in selective coupling at the electrophilic carbon (R
      X) and no reaction at the nucleophilic carbon (R-[M]) for organoboron (-Bpin),
      organotin (-SnMe(3)), and organosilicon (-SiMe(2)OH) containing organic halides
      (X-R-[M]). A Hammett study showed a linear correlation of sigma and sigma(-)
      parameters with the relative rate of reaction of substituted aryl bromides with
      bromoalkanes. The small rho values for these correlations (1.2-1.7) indicate that
      oxidative addition of the bromoarene is not the turnover-frequency determining
      step. The rate of reaction has a positive dependence on the concentration of
      alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing
      agent), and an inverse dependence upon aryl halide concentration. These results
      and studies with an organic reductant (TDAE) argue against the intermediacy of
      organozinc reagents.

PMID- 22463691
TI  - Adipogenesis: from stem cell to adipocyte.
AB  - Excessive caloric intake without a rise in energy expenditure promotes adipocyte
      hyperplasia and adiposity. The rise in adipocyte number is triggered by signaling
      factors that induce conversion of mesenchymal stem cells (MSCs) to preadipocytes
      that differentiate into adipocytes. MSCs, which are recruited from the vascular
      stroma of adipose tissue, provide an unlimited supply of adipocyte precursors.
      Members of the BMP and Wnt families are key mediators of stem cell commitment to
      produce preadipocytes. Following commitment, exposure of growth-arrested
      preadipocytes to differentiation inducers [insulin-like growth factor 1 (IGF1),
      glucocorticoid, and cyclic AMP (cAMP)] triggers DNA replication and reentry into
      the cell cycle (mitotic clonal expansion). Mitotic clonal expansion involves a
      transcription factor cascade, followed by the expression of adipocyte genes.
      Critical to these events are phosphorylations of the transcription factor CCATT
      enhancer-binding protein beta (C/EBPbeta) by MAP kinase and GSK3beta to produce a
      conformational change that gives rise to DNA-binding activity. "Activated"
      C/EBPbeta then triggers transcription of peroxisome proliferator-activated
      receptor-gamma (PPARgamma) and C/EBPalpha, which in turn coordinately activate
      genes whose expression produces the adipocyte phenotype.

PMID- 22463692
TI  - Membrane fission: the biogenesis of transport carriers.
AB  - Membrane-bound transport carriers are used to transfer cargo between membranes of
      the secretory and the endocytic pathways. The generation of these carriers can be
      classified into three steps: segregation of cargo away from the residents of a
      donor compartment (cargo sorting), generation of membrane curvature commensurate
      with the size of the cargo (membrane budding or tubulation), and finally
      separation of the nascent carrier from the donor membrane by a scission or
      membrane fission event. This review summarizes advances in our understanding of
      some of the best-characterized proteins required for the membrane fission that
      separates a transport carrier from its progenitor compartment: the large GTPase
      dynamin, the small guanine nucleotide-binding (G) proteins of the Arf family, BAR
      (Bin-amphiphysin-Rvs) domain proteins, and protein kinase D. These proteins share
      their ability to insert into membranes and oligomerize to create the large
      curvatures; however, the overall process of fission that involves these proteins
      appears to be quite different.

PMID- 22463690
TI  - GTPase networks in membrane traffic.
AB  - Members of the Rab or ARF/Sar branches of the Ras GTPase superfamily regulate
      almost every step of intracellular membrane traffic. A rapidly growing body of
      evidence indicates that these GTPases do not act as lone agents but are networked
      to one another through a variety of mechanisms to coordinate the individual
      events of one stage of transport and to link together the different stages of an
      entire transport pathway. These mechanisms include guanine nucleotide exchange
      factor (GEF) cascades, GTPase-activating protein (GAP) cascades, effectors that
      bind to multiple GTPases, and positive-feedback loops generated by exchange
      factor-effector interactions. Together these mechanisms can lead to an ordered
      series of transitions from one GTPase to the next. As each GTPase recruits a
      unique set of effectors, these transitions help to define changes in the
      functionality of the membrane compartments with which they are associated.

PMID- 22463694
TI  - The development and testing of a new communication tool to help clinicians inform
      patients with obstructive sleep apnoea syndrome about treatment options.
AB  - The objective of this study was to develop a tool to help clinicians inform
      patients about mechanical treatment options, continuous positive airway pressure
      and oral appliances for obstructive sleep apnoea syndrome, and to assess its
      validity, reliability and acceptability. Continuous positive airway pressure is
      always indicated as a first-line treatment in patients with severe obstructive
      sleep apnoea syndrome. However, oral appliances might be an effective treatment
      option in patients who fail treatment attempts, and also as a first-line
      treatment for patients with mild to moderate obstructive sleep apnoea. To help
      patients choose their initial treatment, we developed an electronic decision
      board to present information regarding the potential benefits and side effects of
      the two treatment options, using the best available evidence. In 34 healthy
      volunteers, to test validity we evaluated the extent to which the respondents'
      preferences for a treatment changed predictably when the rate of effectiveness
      and side effects were modified. Reliability was tested by readministering the
      decision board 2 weeks afterwards (kappa test). The decision-board acceptability
      was evaluated in 99 consecutive patients newly diagnosed with obstructive sleep
      apnoea syndrome. We found that the decision board was valid. Reliability was
      excellent (kappa = 0.94). Concerning acceptability, 72% of the patients were
      satisfied with the information provided in the decision board and 71% indicated
      that it helped them to make a decision. The average score of true/false test of
      knowledge was 7.9 of 10 (range 3-10). The decision board we developed is a valid,
      reliable and acceptable tool to assess patients' preferences.

PMID- 22463695
TI  - Preparation of c-Cyclopentadienylcobalt(III) and c-Cyclopentadienylnickel(IV)
      Complexes of the c-7-B(10)CH(11)(3-) Carbollide Ligand.

PMID- 22463693
TI  - Neuropathological, clinical and molecular pathology in female fragile X
      premutation carriers with and without FXTAS.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset
      neurodegenerative disorder associated with premutation alleles of the fragile X
      mental retardation 1 (FMR1) gene. Approximately 40% of older male premutation
      carriers, and a smaller proportion of females, are affected by FXTAS; due to the
      lower penetrance the characterization of the disorder in females is much less
      detailed. Core clinical features of FXTAS include intention tremor, cerebellar
      gait ataxia and frequently parkinsonism, autonomic dysfunction and cognitive
      deficits progressing to dementia in up to 50% of males. In this study, we report
      the clinical, molecular and neuropathological findings of eight female
      premutation carriers. Significantly, four of these women had dementia; of the
      four, three had FXTAS plus dementia. Post-mortem examination showed the presence
      of intranuclear inclusions in all eight cases, which included one asymptomatic
      premutation carrier who died from cancer. Among the four subjects with dementia,
      three had sufficient number of cortical amyloid plaques and neurofibrillary
      tangles to make Alzheimer's disease a highly likely cause of dementia and a
      fourth case had dementia with cortical Lewy bodies. Dementia appears to be more
      common than originally reported in females with FXTAS. Although further studies
      are required, our observation suggests that in a portion of FXTAS cases there is
      Alzheimer pathology and perhaps a synergistic effect on the progression of the
      disease may occur.

PMID- 22463696
TI  - A role of autophagy in Trypanosoma brucei cell death.
AB  - The early branching eukaryote Trypanosoma brucei contains functional autophagy
      machinery that allows regulated degradation of its own cellular components. In
      this study, we examined the function of two Atg8 genes, TbAtg8.1 and TbAtg8.2, in
      starvation-induced autophagosome formation and cell death in procyclic T. brucei.
      Upon starvation, both TbAtg8.1 and TbAtg8.2 localize to punctate structures
      characteristic of autophagosomes as shown by fluorescence and electron
      microscopy, and wortmannin and chloroquine treatments. While TbAtg8.1 depletion
      has no detectable effects on TbAtg8.2 recruitment to autophagosomes, TbAtg8.2
      depletion greatly reduced the autophagosome relocation of TbAtg8.1. Depletion of
      TbAtg8.1 and 8.2, individually or together, promote cell survival under
      starvation conditions. Taken together, these observations confirm the presence of
      an autophagy-related cell death pathway in T. brucei, where TbAtg8.1 and TbAtg8.2
      play essential but distinct roles in autophagosome formation and cell death.

PMID- 22463697
TI  - Association of polymorphisms in the estrogen receptor beta (ESR2) with
      unexplained recurrent spontaneous abortion (URSA) in Chinese population.
AB  - OBJECTIVES: To investigate the association of 1082G > A(RsaI) (rs1256049) and
      1730A > G(AluI) (rs4986938) single nucleotide polymorphisms(SNPs), respectively -
      located on estrogen receptor beta (ESR2) gene with recurrent spontaneous abortion
      (RSA) in Chinese population. METHODS: The study group consisted of 196 patients
      with RSA and 182 fertile women as control. Two functional polymorphisms 1082G > A
      (a silent mutation in exon 5) and 1730A > G (3' nontranslated region of the exon
      8) of ESR2 were studied by association analysis. RESULTS: There were no
      significant differences between ESR2 gene polymorphisms and RSA (chi(2) =1.793,
      P=0.408; chi(2) =.432, P=0.489, respectively). CONCLUSION: The present data
      indicate that the studied SNPs on ESR2 gene may not be associated with RSA in
      Chinese population.

PMID- 22463698
TI  - The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis -
      sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST
      ASSURE) trial: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Second-generation drug-eluting stents (DES) have raised the bar of
      clinical performance. These stents are mostly made from cobalt chromium alloy. A
      newer generation DES has been developed from platinum chromium alloy, but
      clinical data regarding the efficacy and safety of the platinum chromium-based
      everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against
      the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an
      antiplatelet regimen is an integral component of medical therapy after
      percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose
      of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve
      outcome at 1 month compared with conventional dose in acute coronary syndrome
      (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of
      cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than
      doubling the dose of clopidogrel in high-risk patients. METHODS: In the
      'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety
      & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE)
      trial, approximately 3,750 patients are being prospectively and randomly assigned
      in a 2 * 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES)
      and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target
      lesion failure at 1 year for the stent comparison, and the second primary
      endpoint is net clinical outcome at 1 month for comparison of antiplatelet
      therapy regimen. DISCUSSION: The HOST-ASSURE trial is the largest study yet
      performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr
      ZES in an 'all-comers' population. In addition, this study will also compare the
      clinical outcome of TAT versus DDAT for 1-month post PCI. TRIAL REGISTRATION:
      ClincalTrials.gov number NCT01267734.

PMID- 22463699
TI  - Central vagal activation by alpha(2) -adrenergic stimulation is impaired in
      spontaneously hypertensive rats.
AB  - AIM: To elucidate the abnormality of vagal control in spontaneously hypertensive
      rats (SHR) by measuring left ventricular myocardial interstitial acetylcholine
      (ACh) release in response to alpha(2) -adrenergic stimulation as an index of in
      vivo vagal nerve activity. METHODS: A cardiac microdialysis technique was applied
      to the rat left ventricle in vivo, and the effect of alpha(2) -adrenergic
      stimulation by medetomidine or electrical vagal nerve stimulation on myocardial
      interstitial ACh levels was examined in normotensive Wistar-Kyoto rats (WKY) and
      SHR under anaesthetized conditions. RESULTS: Intravenous medetomidine (0.1 mg kg(
      1) ) significantly increased the ACh levels in WKY (from 2.4 +/- 0.6 to 4.2 +/-
      1.3 nmol L(-1) , P < 0.05, n = 7) but not in SHR (from 2.5 +/- 0.7 to 2.7 +/- 0.7
      nmol L(-1) , n = 7). In contrast, electrical vagal nerve stimulation increased
      the ACh levels in both WKY (from 1.0 +/- 0.4 to 2.9 +/- 0.9 nmol L(-1) , P <
      0.001, n = 6) and SHR (from 0.9 +/- 0.2 to 2.2 +/- 0.4 nmol L(-1) , P < 0.001, n
      = 6). Intravenous administration of medetomidine (0.1 mg kg(-1) ) did not affect
      the vagal nerve stimulation-induced ACh release in either WKY or SHR. CONCLUSION:
      Medetomidine-induced central vagal activation was impaired in SHR, whereas
      peripheral vagal control of ACh release was preserved. In addition to abnormal
      sympathetic control, vagal control by the central nervous system may be impaired
      in SHR.

PMID- 22463700
TI  - Prevalences of overweight and obesity among children in remote Aboriginal
      communities in central Australia.
AB  - INTRODUCTION: The chronic diseases associated with overweight and obesity are
      major contributors to the excess disease burden of Aboriginal Australians.
      Surveillance of overweight and obesity is required to monitor these conditions,
      and to develop and evaluate interventions to improve health and wellbeing. Remote
      Aboriginal communities in Australia's Northern Territory (NT) are where
      approximately two-thirds of the NT Aboriginal people live, a proportion which has
      been stable over many years. However the remote communities suffer significant
      socioeconomic disadvantage including limited education and employment
      opportunities, and poor quality and overcrowded housing. Approximately one-third
      of Aboriginal people in NT live in central Australia, which consists of the Alice
      Springs and Barkly districts. The Healthy School-Aged Kids Program includes
      health promotion and child health screening, and is run in remote Aboriginal
      communities of NT. This report provides estimates of prevalences of overweight
      and obesity among children in central Australia who participated in health checks
      as part of Healthy School-Aged Kids Program in 2010. METHODS: All children in
      remote central Australian Aboriginal communities were invited to participate in
      health checks. Children who attended were weighed and measured. Date of birth,
      sex, height and weight for each child were used to determine prevalence of
      overweight (>=+1 standard deviation [SD] BMI-for-age) and obesity (>=+2 SD BMI
      for-age) according to WHO Growth standards. Differences in proportions of
      overweight and obesity by age group and sex, and their statistical significance
      were calculated. RESULTS: Weight, height, sex and age data were available for 996
      children from a population of 1764. It was found that 22.1% of girls and 20.7% of
      boys were overweight; and 5.1% of girls and 5.8% of boys were obese as defined by
      BMI-for-age. Prevalence of overweight but not obesity increased with age (for
      overweight z=3.28, p=0.0011; for obesity z=0.68; p=0.50). CONCLUSION: The
      prevalences of overweight and obesity as estimated by BMI-for-age among children
      in remote central Australian Aboriginal communities were compared with those in
      other Australian surveys. They appear unlikely to reflect future relative risk of
      the chronic diseases with which overweight and obesity are associated. Routine
      collection of data on BMI-for-age may not provide adequate estimation of future
      risk of chronic disease burden attributable to overweight and obesity among these
      children. Alternative measures for surveillance for overweight such as waist
      circumference may prove more useful. Appropriate interventions to reduce risk of
      chronic disease are required, including interventions to reduce prevalences of
      overweight and obesity.

PMID- 22463701
TI  - Allogeneic stem cell transplantation for myelofibrosis in 2012.
AB  - Myelofibrosis (MF) is a heterogeneous disease for which long-term, effective
      medical therapeutic options are currently limited. The role of allogeneic
      haematopoietic stem cell transplant (AHSCT) in this population, many of whom are
      elderly, often provides a challenge with regard to the identification of suitable
      candidates, timing of transplantation in the disease course and choice of
      conditioning regimen. This review summarizes key findings from published data
      concerning AHSCT in MF and attempts to provide a state of the art approach to MF
      AHSCT in 2012. In addition, we postulate on how the era of JAK inhibition might
      impact on transplantation for MF.

PMID- 22463702
TI  - High level of Ets-related gene expression has high specificity for prostate
      cancer: a tissue microarray study of 11 483 cancers.
AB  - AIMS: TMPRSS2-ERG fusion resulting in strong Ets-related gene (ERG)
      overexpression occurs in about 50% of prostate cancers. This study was undertaken
      to determine the prevalence of ERG overexpression in other tumour types as well
      as in normal tissues. METHODS AND RESULTS: A total of 11 483 tumours and 72
      different normal tissue types were analysed in a tissue microarray format. Strong
      nuclear ERG overexpression was found in 36.7% of prostate carcinomas as well as
      in various vascular tumours, including Kaposi sarcomas (91.7%), angiosarcomas
      (100%) and haemangiomas (90.9%). Moderate to strong nuclear ERG immunostaining
      was also observed in thymoma (6.1%). Weak to moderate ERG staining was found in a
      small number of squamous cell carcinomas of the skin, squamous carcinomas of the
      lung, malignant mesotheliomas, carcinosarcomas of the uterus, gastrointestinal
      stromal tumours, hepatocellular carcinomas, teratomas of the testis, anaplastic
      carcinomas of the thyroid, giant cell tumours of the tendon sheath and benign
      fibrous histiocytomas of the skin. ERG overexpression was not seen in 8886
      samples from 132 other tumour types and subtypes. Within normal tissues,
      immunohistochemically detectable ERG overexpression was restricted to endothelial
      cells and subsets of lymphocytes. CONCLUSIONS: The high specificity of ERG
      expression in both normal and neoplastic tissues suggests a very narrow
      biological role for ERG in highly selected tissues.

PMID- 22463703
TI  - Small proteins link coat and cortex assembly during sporulation in Bacillus
      subtilis.
AB  - Mature spores of the bacterium Bacillus subtilis are encased by two concentric
      shells: an inner shell (the 'cortex'), made of peptidoglycan; and an outer
      proteinaceous shell (the 'coat'), whose basement layer is anchored to the surface
      of the developing spore via a 26-amino-acid-long protein called SpoVM. During
      sporulation, initiation of cortex assembly depends on the successful initiation
      of coat assembly, but the mechanisms that co-ordinate the morphogenesis of both
      structures are largely unknown. Here, we describe a sporulation pathway involving
      SpoVM and a 37-amino-acid-long protein named 'CmpA' that is encoded by a
      previously un-annotated gene and is expressed under control of two sporulation
      specific transcription factors (sigma(E)  and SpoIIID). CmpA localized to the
      surface of the developing spore and deletion of cmpA resulted in cells
      progressing through the sporulation programme more quickly. Overproduction of
      CmpA did not affect normal growth or cell division, but delayed entry into
      sporulation and abrogated cortex assembly. In those cells that had successfully
      initiated coat assembly, CmpA was removed by a post-translational mechanism,
      presumably in order to overcome the sporulation inhibition it imposed. We propose
      a model in which CmpA participates in a developmental checkpoint that ensures the
      proper orchestration of coat and cortex morphogenesis by repressing cortex
      assembly until coat assembly successfully initiates.

PMID- 22463704
TI  - Apparent temperature and acute myocardial infarction hospital admissions in
      Copenhagen, Denmark: a case-crossover study.
AB  - BACKGROUND: The influence of temperature on acute myocardial infarction (AMI) has
      not been investigated as extensively as the effects of broader outcomes of
      morbidity and mortality. Sixteen studies reported inconsistent results and two
      considered confounding by air pollution. We addressed some of the methodological
      limitations of the previous studies in this study. METHODS: This is the first
      study of the association between the daily 3-hour maximum apparent temperature
      (Tapp(max)) and AMI hospital admissions in Copenhagen. The study period covered 1
      January 1999-31 December 2006, stratified in warm (April-September) and cold
      (October-March) periods. A case-crossover epidemiology study design was applied.
      Models were adjusted for public holidays and influenza, confounding by PM10, NO2
      and CO was investigated, the lag and non-linear effects of Tapp(max) was
      examined, effect modification by age, sex and SES was explored, and the results
      of the case-crossover models were compared to those of the generalised additive
      Poisson time-series and generalised estimating equation models. RESULTS: 14,456
      AMI hospital admissions (12,995 people) occurred during the study period. For an
      inter-quartile range (6 or 7 degrees C) increase in the 5-day cumulative average
      of Tapp(max), a 4% (95% CI:-2%; 10%) and 9% (95% CI: 3%; 14%) decrease in the AMI
      admission rate was observed in the warm and cold periods, respectively. The 19-65
      year old group, men and highest SES group seemed to be more susceptible in the
      cold period. CONCLUSION: An increase in Tapp(max) is associated with a decrease
      in AMI admissions during the colder months.

PMID- 22463705
TI  - Determination of inflammatory biomarkers in patients with COPD: a comparison of
      different assays.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory
      pulmonary disorder with systemic inflammatory manifestations that are mediated by
      circulating acute-phase reactants. This study compared an enzyme-linked
      immunosorbent assay (ELISA) to a nephelometric technique for the measurement of
      serum C-reactive protein (CRP) and serum amyloid A (SAA) and investigated how the
      choice of assay influenced the estimation of inflammation in patients with stable
      COPD. METHODS: CRP and SAA concentrations measured by ELISA and nephelometry in
      88 patients with COPD and 45 control subjects were used to evaluate the
      performance of these methods in a clinical setting. RESULTS: With both assays,
      the concentrations of CRP and SAA were higher in COPD patients than in controls
      after adjustment for age and sex. There was a moderate correlation between the
      values measured by ELISA and those measured by nephelometry (logCRP: r = 0.55, p
      < 0.001; logSAA: r = 0.40, p < 0.001). However, the concentrations of biomarkers
      determined by nephelometry were significantly higher than those obtained with
      ELISA for CRP (mean difference = 2.7 (9.4) mg/L) and SAA (mean difference = 0.31
      (14.3) mg/L). CONCLUSION: Although the serum CRP and SAA concentrations measured
      by ELISA and nephelometry correlated well in COPD patients, the ELISA values
      tended to be lower for CRP and SAA when compared with nephelometric measurements.
      International standardization of commercial kits is required before the
      predictive validity of inflammatory markers for patients with COPD can be
      effectively assessed in clinical practice.

PMID- 22463707
TI  - Connective tissue grafts in conjunction with implants installed immediately into
      extraction sockets. An experimental study in dogs.
AB  - AIM: To evaluate the influence of a sub-epithelial connective tissue graft placed
      at the buccal aspect of implants installed immediately after tooth extraction on
      the dimensional changes of hard and soft tissues. MATERIALS AND METHODS: In six
      Labrador dogs a bilateral partial- thickness dissection was made buccal to the
      second mandibular premolar. At the lingual aspect, full-thickness flaps were
      elevated. The teeth were extracted and implants installed immediately into the
      distal socket. A connective tissue graft was obtained from the palate and applied
      to the buccal aspect of the test sites, whereas contra-laterally, no graft was
      applied. The flaps were sutured to allow a non-submerged installation. After 4
      months of healing, the animals were sacrificed, ground sections were obtained and
      histomorphometric analyses were performed. RESULTS: After 4 months of healing,
      all implants were integrated (n = 6). Both at the test and at the control sites
      bone resorption occurred: 1.6 mm and 2.1 mm, respectively. The difference was not
      statistically significant. The coronal aspect of the peri-implant soft tissue was
      wider and located more coronally at the test compared with the control sites. The
      differences were statistically significant. CONCLUSIONS: The application of a
      connective tissue graft placed at the buccal aspect of the bony wall at implants
      installed immediately after tooth extraction yielded a minimal preservation of
      the hard tissues. The peri-implant mucosa, however, was significantly thicker and
      more coronally positioned at the test compared with the control sites.

PMID- 22463706
TI  - Improvements of insulin resistance in ovariectomized rats by a novel
      phytoestrogen from Curcuma comosa Roxb.
AB  - BACKGROUND: Curcuma comosa Roxb. (C. comosa) is an indigenous medicinal herb that
      has been used in Thailand as a dietary supplement to relieve postmenopausal
      symptoms. Recently, a novel phytoestrogen, (3R)-1,7-diphenyl-(4E,6E)-4,6
      heptadien-3-ol or compound 049, has been isolated and no study thus far has
      investigated the role of C. comosa in preventing metabolic alterations occurring
      in estrogen-deprived state. The present study investigated the long-term effects
      (12 weeks) of C. comosa hexane extract and compound 049 on insulin resistance in
      prolonged estrogen-deprived rats. METHODS: Female Sprague-Dawley rats were
      ovariectomized (OVX) and treated with C. comosa hexane extract (125 mg, 250 mg,
      or 500 mg/kg body weight (BW)) and compound 049 (50 mg/kg BW) intraperitoneally
      three times per week for 12 weeks. Body weight, food intake, visceral fat weight,
      uterine weight, serum lipid profile, glucose tolerance, insulin action on
      skeletal muscle glucose transport activity, and GLUT-4 protein expression were
      determined. RESULTS: Prolonged ovariectomy resulted in dyslipidemia, impaired
      glucose tolerance and insulin-stimulated skeletal muscle glucose transport, as
      compared to SHAM. Treatment with C. comosa hexane extract and compound 049, three
      times per week for 12 weeks, markedly reduced serum total cholesterol and low
      density lipoprotein levels, improved insulin sensitivity and partially restored
      uterine weights in ovariectomized rats. In addition, compound 049 or high doses
      of C. comosa hexane extract enhanced insulin-mediated glucose uptake in skeletal
      muscle and increased muscle GLUT-4 protein levels. CONCLUSIONS: Treatment with C.
      comosa and its diarylheptanoid derivative improved glucose and lipid metabolism
      in estrogen-deprived rats, supporting the traditional use of this natural
      phytoestrogen as a strategy for relieving insulin resistance and its related
      metabolic defects in postmenopausal women.

PMID- 22463708
TI  - Evaluation of vancomycin and gentamicin dialysis clearance using in vivo and in
      vitro systems.
AB  - Advances in hemodialysis (HD) techniques have increased the potential for drug
      removal. Quantifying drug clearance in clinical studies for all possible dialysis
      conditions is impractical, given the variability in dialysis conditions. The
      purpose of this study was to determine the dialysis clearance (CL(D)) of
      vancomycin and gentamicin using in vitro and in vivo methods and evaluate the
      applicability of in vitro data. In vitro dialysis was used to determine the CL(D)
      of vancomycin and gentamicin under conditions of intermittent HD (IHD) and
      sustained low-efficiency dialysis (SLED). Two Fresenius polysulfone dialyzers
      were studied: F180NR for IHD and F50 for SLED. Data were compared with in vivo
      CL(D) determined in patients with end-stage renal disease receiving IHD and from
      the literature for SLED. Under IHD conditions, in vitro CL(D) of vancomycin and
      gentamicin was 131 +/- 3 and 154 +/- 3 mL/min, respectively, and under SLED
      condition it was 72 +/- 9 and 84 +/- 11 mL/min, respectively. These values were
      11-27% higher than in vivo CL(D) for IHD (103 +/- 15 mL/min for vancomycin and
      132 +/- 25 mL/min for gentamicin) and SLED (63 mL/min for vancomycin and 76 +/-
      38 mL/min for gentamicin). There was a statistically significant difference in
      vancomycin clearance by IHD for the in vitro study compared with in vivo data (p
      = 0.012), but not for gentamicin (p = 0.18). In vitro methods overestimated in
      vivo CL(D), but are reasonable to assist with drug regimen design if one
      considers the limitations.

PMID- 22463709
TI  - A watershed approach for improving medical image segmentation.
AB  - In this paper, a novel watershed approach based on seed region growing and image
      entropy is presented which could improve the medical image segmentation. The
      proposed algorithm enables the prior information of seed region growing and image
      entropy in its calculation. The algorithm starts by partitioning the image into
      several levels of intensity using watershed multi-degree immersion process. The
      levels of intensity are the input to a computationally efficient seed region
      segmentation process which produces the initial partitioning of the image
      regions. These regions are fed to entropy procedure to carry out a suitable
      merging which produces the final segmentation. The latter process uses a region
      based similarity representation of the image regions to decide whether regions
      can be merged. The region is isolated from the level and the residual pixels are
      uploaded to the next level and so on, we recall this process as multi-level
      process and the watershed is called multi-level watershed. The proposed algorithm
      is applied to challenging applications: grey matter-white matter segmentation in
      magnetic resonance images (MRIs). The established methods and the proposed
      approach are experimented by these applications to a variety of simulating
      immersion, multi-degree, multi-level seed region growing and multi-level seed
      region growing with entropy. It is shown that the proposed method achieves more
      accurate results for medical image oversegmentation. 

PMID- 22463710
TI  - Efficient construction of fused indolines with a 2-quaternary center via an
      intramolecular Heck reaction with a low catalyst loading.
AB  - An efficient construction of fused indolines with a 2-quaternary center through a
      palladium-catalyzed intramolecular Heck reaction of N-(2(2-halobenzoxyl)-2,3
      disubstituted indoles is disclosed. This protocol provided a straightforward
      access to diverse fused indolines with good functional group tolerance.

PMID- 22463711
TI  - Modeling the local biodiversity impacts of agricultural water use: case study of
      a wetland in the coastal arid area of Peru.
AB  - Global water use is dominated by agriculture and has considerable influence on
      people's livelihood and ecosystems, especially in semiarid and arid regions.
      Methods to address the impacts of water withdrawal and consumption on terrestrial
      and aquatic ecosystems within life cycle assessment are still sparse and very
      generic. Regionalized characterization factors (CFs) for a groundwater-fed
      wetland at the arid coast of Peru are developed for groundwater and surface water
      withdrawal and consumption in order to address the spatial dependency of water
      use related impacts. Several agricultural scenarios for 2020 were developed in a
      workshop with local stakeholders and used for calculating total biodiversity
      impacts. In contrast to assumptions used in top-down approaches (e.g., Pfister et
      al. Environ. Sci Technol. 2009, 43, 4098 ), irrigation with surface water leads
      in this specific region to benefits for the groundwater-fed wetland, due to
      additional groundwater recharge from surplus irrigation water. However,
      irrigation with groundwater leads to ecological damage to the wetland. The CFs
      derived from the different scenarios are similar and can thus be used as general
      CFs for this region, helping local decision-makers to plan future agricultural
      development, including irrigation technologies, crop choices, and protection of
      the wetland.

PMID- 22463712
TI  - Yield-related QTLs and their applications in rice genetic improvement.
AB  - Grain yield is one of the most important indexes in rice breeding, which is
      governed by quantitative trait loci (QTLs). Different mapping populations have
      been used to explore the QTLs controlling yield related traits. Primary
      populations such as F(2) and recombinant inbred line populations have been widely
      used to discover QTLs in rice genome-wide, with hundreds of yield-related QTLs
      detected. Advanced populations such as near isogenic lines (NILs) are efficient
      to further fine-map and clone target QTLs. NILs for primarily identified QTLs
      have been proposed and confirmed to be the ideal population for map-based
      cloning. To date, 20 QTLs directly affecting rice grain yield and its components
      have been cloned with NIL-F(2) populations, and 14 new grain yield QTLs have been
      validated in the NILs. The molecular mechanisms of a continuously increasing
      number of genes are being unveiled, which aids in the understanding of the
      formation of grain yield. Favorable alleles for rice breeding have been 'mined'
      from natural cultivars and wild rice by association analysis of known functional
      genes with target trait performance. Reasonable combination of favorable alleles
      has the potential to increase grain yield via use of functional marker assisted
      selection.

PMID- 22463713
TI  - Modeling forest stand dynamics from optimal balances of carbon and nitrogen.
AB  - We formulate a dynamic evolutionary optimization problem to predict the optimal
      pattern by which carbon (C) and nitrogen (N) are co-allocated to fine-root, leaf,
      and wood production, with the objective of maximizing height growth rate, year by
      year, in an even-aged stand. Height growth is maximized with respect to two
      adaptive traits, leaf N concentration and the ratio of fine-root mass to sapwood
      cross-sectional area. Constraints on the optimization include pipe-model
      structure, the C cost of N acquisition, and agreement between the C and N
      balances. The latter is determined by two models of height growth rate, one
      derived from the C balance and the other from the N balance; agreement is defined
      by identical growth rates. Predicted time-courses of maximized height growth rate
      accord with general observations. Across an N gradient, higher N availability
      leads to greater N utilization and net primary productivity, larger trees, and
      greater stocks of leaf and live wood biomass, with declining gains as a result of
      saturation effects at high N availability. Fine-root biomass is greatest at
      intermediate N availability. Predicted leaf and fine-root stocks agree with data
      from coniferous stands across Finland. Optimal C-allocation patterns agree with
      published observations and model analyses.

PMID- 22463714
TI  - Electron spin resonance study of  o(2)(+) salts.  influence of crystal field
      effects and relaxation.

PMID- 22463715
TI  - Inter-relationship of plasma markers of oxidative stress and thyroid hormones in
      schizophrenics.
AB  - BACKGROUND: The relationship of oxidative stress to thyroid hormones has not been
      studied in the schizophrenics. The present study determined the status and
      interrelationship of plasma markers of oxidative stress, nitric oxide and thyroid
      hormones in thirty (17 males and 13 females) newly diagnosed patients with acute
      schizophrenia before initiation of chemotherapy. Twenty five (13 males and 12
      females) mentally healthy individuals served as controls. Patients and controls
      with history of hard drugs (including alcohol and cigarette), pre-diagnosis
      medications (e.g. antiparkinsonian/antipsychotic drugs), chronic infections,
      liver disease and diabetes mellitus were excluded from the study. Plasma levels
      of total antioxidant potential (TAP), total plasma peroxides (TPP), nitric oxide
      (NO), malondialdehyde (MDA), thyroxine (T4), tri-iodothyronine (T3) and thyroid
      stimulating hormone (TSH) were determined in all participants using
      spectrophotometric and enzyme linked immunosorbent assay (ELISA) methods
      respectively. Oxidative stress index (OSI) was calculated as the percent ratio of
      total plasma peroxides and total antioxidant potential. FINDINGS: Significantly
      higher plasma levels of MDA (p < 0.01), TPP (p < 0.01), OSI (p < 0.01), T3 (p <
      0.01) and T4 (p < 0.05) were observed in schizophrenics when compared with the
      controls. The mean levels of TAP, NO and TSH were significantly lower in
      schizophrenics (p < 0.01) when compared with the controls. The result shows that
      T3 values correlate significantly with MDA (p < 0.05) and TPP (p < 0.01) in
      schizophrenics. CONCLUSIONS: Higher level of TPP may enhance thyroid hormogenesis
      in schizophrenics. Adjuvant antioxidant therapy may be a novel approach in the
      treatment of schizophrenic patients.

PMID- 22463716
TI  - Interferon-gamma signals via an ERK1/2-ARF6 pathway to promote bacterial
      internalization by gut epithelia.
AB  - The barrier function of the epithelium lining the intestine is essential for
      health by preventing the free passage of colonic bacteria into the mucosa.
      Epithelia treated with interferon (IFN)-gamma display increased bacteria
      transcytosis. Much is known of how IFNgamma affects the tight junction and
      paracellular permeability, yet its role in modifying transcellular traffic of
      commensal bacteria remains poorly understood. Using immunoblotting, ELISA and
      immunolocalization, IFNgamma was found to activate extracellular regulated kinase
      (ERK)1/2 in the human colon-like T84 epithelial cell line. Pharmacological
      inhibition of MEK/ERK1/2 signalling with U0126 significantly inhibited IFNgamma
      induced increases in the transcytosis of non-invasive Escherichia coli (strain
      HB101). IFNgamma treatment enhanced epithelial internalization of E. coli, some
      of which subsequently escaped the enterocyte. Molecular analyses revealed that
      ERK1/2 inhibition prevented activation of the ADP-ribosylation factor (ARF)-6, a
      protein associated with endocytosis, and that siRNA knock-down of ARF6 expression
      reduced IFNgamma-induced E. coli internalization into T84 cells. None of these
      interventions affected the drop in transepithelial resistance caused by IFNgamma.
      Thus, increased transcellular passage may be a major component of IFNgamma
      induced increases in epithelial permeability, and ERK1/2 and ARF6 are presented
      as important molecules in IFNgamma-evoked transcytosis of bacteria across gut
      epithelia.

PMID- 22463717
TI  - Impact of the N-terminal amino acid on the formation of pyrazines from peptides
      in Maillard model systems.
AB  - Only a minor part of Maillard reaction studies in the literature focused on the
      reaction between carbohydrates and peptides. Therefore, in continuation of a
      previous study in which the influence of the peptide C-terminal amino acid was
      investigated, this study focused on the influence of the peptide N-terminal amino
      acid on the production of pyrazines in model reactions of glucose, methylglyoxal,
      or glyoxal. Nine different dipeptides and three tripeptides were selected. It was
      shown that the structure of the N-terminal amino acid is determinative for the
      overall pyrazine production. Especially, the production of 2,5(6)
      dimethylpyrazine and trimethylpyrazine was low in the case of proline, valine, or
      leucine at the N-terminus, whereas it was very high for glycine, alanine, or
      serine. In contrast to the alkyl-substituted pyrazines, unsubstituted pyrazine
      was always produced more in the case of experiments with free amino acids. It is
      clear that different mechanisms must be responsible for this observation. This
      study clearly illustrates the capability of peptides to produce flavor compounds
      such as pyrazines.

PMID- 22463718
TI  - Vacuum-assisted vaginal delivery simulation--quantitation of subjective measures
      of traction and detachment forces.
AB  - OBJECTIVE: Excessive traction has been alleged as the cause of newborn
      complications associated with vacuum delivery. We sought to quantify subjective
      levels of physician vacuum traction in a simulated obstetric delivery model,
      dependent upon level of training. METHODS: Three groups of physicians, based on
      training level applied traction (minimal, average, maximal) on a pre-applied
      vacuum model and forces were continually recorded. Detachment force was recorded
      with traction in both the pelvic axis and at an oblique angle. RESULTS:
      Quantified traction force increased from subjective minimal to average to maximal
      pulls. Within each level, there were no differences between the groups in the
      average traction force. Detachment force was significantly less when traction was
      applied at an oblique angle as opposed to the pelvic axis (11.1 +/- 0.3 vs 12.2
      +/- 0.3 kg). CONCLUSION: Providers appear to be good judges of the force being
      applied, as a clear escalation in force is noted with minimal, average and
      maximal force pulls. There appears to be a relatively short learning curve for
      use of the vacuum, as junior residents' applied force was not different from
      those of more experienced practitioners. Using the KIWI device, detachment force
      is lower when traction is applied at an oblique angle.

PMID- 22463719
TI  - Ligand-assisted enhancement of CO2 capture in metal-organic frameworks.
AB  - Using density functional theory with a van der Waals-corrected functional, we
      elucidate how CO(2) binds to a novel "BTT-type" metal-organic framework (MOF)
      featuring open metal centers. We show that CO(2) binds most favorably to open
      metal cation sites, but with an adsorption energy that can be three times more
      sensitive to the choice of the bridging ligand than to metal cation choice. A
      strong, three-site interaction between CO(2) and the open-metal site is
      predicted, with the binding energy enhanced by up to a factor of 2, depending on
      the ligand. The CO(2)-MOF binding can be attributed to a combination of
      electrostatics and vdW dispersive interactions, both of which are critically
      sensitive to the local environment, and both of which contribute nearly equally
      to the overall binding strength. We show that a judicious choice of the organic
      linker and the metal center allows the binding energy to be tuned from 34.8
      kJ/mol (for CaBTTri) to a maximum of 64.5 kJ/mol (MgBTT).

PMID- 22463720
TI  - Passive immunization with myelin basic protein activated T cells suppresses
      axonal dieback but does not promote axonal regeneration following spinal cord
      hemisection in adult rats.
AB  - The previous studies suggested that some subpopulations of T lymphocytes against
      central nervous system (CNS) antigens, such as myelin basic protein (MBP), are
      neuroprotective. But there were few reports about the effect of these T cells on
      axon regeneration. In this study, the neonatally thymectomied (Tx) adult rats
      which contain few T lymphocytes were subjected to spinal cord hemisection and
      then passively immunized with MBP-activated T cells (MBP-T). The regeneration and
      dieback of transected axons of cortico-spinal tract (CST) were detected by biotin
      dextran amine (BDA) tracing. The behavioral assessments were performed using the
      Basso, Beattie, and Bresnahan locomotor rating scale. We found that passive
      transferring of MBP-T could attenuate axonal dieback. However, no significant
      axon regeneration and behavioral differences were observed among the normal, Tx
      and sham-Tx (sTx) rats with or without MBP-T passive immunization. These results
      indicate that passive transferring of MBP-T cells can attenuate axonal dieback
      and promote neuroprotection following spinal cord injury (SCI), but may not
      promote axon regeneration.

PMID- 22463721
TI  - Stereotactic radiosurgery to treat presumed Rathke's cleft cysts.
AB  - OBJECTIVE: Stereotactic radiosurgery (SRS) has been developed as a clinical
      treatment method for certain brain tumours that does not need craniotomy. As a
      more accurate radiation technique, SRS can deliver a relatively large dose of
      stereotactic radiation to a conformal target with less normal brain tissue
      irradiated in a single treatment. The aim of this study is to evaluate the
      therapeutic effects of SRS for Rathke's cleft cysts (RCCs). METHODS: SRS was
      performed using a rotating gamma ray unit in seven selected patients with
      symptomatic RCCs diagnosed upon typical MR imaging combined with clinical
      manifestation. The patients included one male and six females with an age range
      from 25 to 63 years (mean 43.4 years). Five patients presented with headache,
      three with menstrual disorder or infertility and one with vision impairment. No
      other endocrine dysfunction was observed. SRS was performed in the patients with
      a central dose varied from 22.6 to 40 Gy (mean 32.5 Gy) and a peripheral dose
      from 9 to 20 Gy (mean 13.4 Gy). RESULTS: The patients were followed up for 11-105
      months (mean 38.6 months) after SRS. All symptoms that presented before treatment
      were relieved within 3-6 months post-SRS and no endocrine dysfunction was
      developed during the follow-up period. MR imaging demonstrated that the RCCs were
      completely disappeared in five cases and significantly shrunken in the other two
      cases. No recurrence was observed in any cases during the follow-up. CONCLUSION:
      This study demonstrates that SRS can treat RCCs effectively without evident side
      effects.

PMID- 22463722
TI  - Molecular neurosurgery: vectors and vector delivery strategies.
AB  - Molecular neurosurgery involves the use of vector-mediated gene therapy and gene
      knockdown to manipulate in vivo gene expression for the treatment of neurological
      diseases. These techniques have the potential to revolutionise the practice of
      neurosurgery. However, significant challenges remain to be overcome before these
      techniques enter routine clinical practice. These challenges have been the
      subject of intensive research in recent years and include the development of
      strategies to facilitate effective vector delivery to the brain and the
      development of both viral and non-viral vectors that are capable of efficient
      cell transduction without excessive toxicity. This review provides an update on
      the practice of molecular neurosurgery with particular focus on the practical
      neurosurgical aspects of vector delivery to the brain. In addition, an
      introduction to the key vectors employed in clinical trials and a brief overview
      of previous gene therapy clinical trials is provided. Finally, key areas for
      future research aimed at increasing the likelihood of the successful translation
      of gene therapy into clinical trials are highlighted.

PMID- 22463723
TI  - Classical to current approach for treatment of psoriasis: a review.
AB  - Psoriasis is a genetic predisposition with T-cell mediated autoimmune
      inflammatory skin disorder, characterized by cutaneous inflammation, increased
      epidermal proliferation, hyperkeratosis, angiogenesis, and abnormal
      keratinization that affects up to 2 - 3% of the population worldwide. Common
      therapies that are used for the treatment of psoriasis include topical, systemic,
      phototherapy, combination, herbal therapy and novel molecules. Topically used
      agents include Vit D, calcipotriol, corticosteroids, dithranol and retinoids etc.
      Systemically used agents include methotrexate and cyclosporine etc. Phototherapy
      includes UV-B, Psoralen plus ultraviolet therapy and excimer laser etc. These
      therapies have a number of potential problems, such as limited in efficacy,
      inconvenience, organ toxicity, carcinogenic and broadband immunosuppression. In
      natural treatment a variety of natural agents such as methanolic extracts of
      duzhong (Eucommia ulmoides Oliv.), yerba mate (Ilex paraguariensis,) linseed oil,
      fish oil, and Indigo naturalis etc., that modulates T cell and cytokine action at
      various steps along with the pathogenic sequence have been developed. But till
      now there is no more in vivo, dose and its efficacy data has been established.
      Current therapy includes biologicals, small molecules inhibitor and enzyme
      inhibitors etc, which serve as novel therapeutic options for psoriasis treatment.
      All these avoid the side effects of the prebiologically developed systemic agents
      including hepatotoxicity, nephrotoxicity, and bone marrow suppression. Currently,
      Denilukin diftitox, Efalizumab, Alefacept, Ustekinumab and Etanercept are
      approved by the FDA, and others molecules are at clinical stage. Patents issued
      by the US office are also included in current psoriasis treatment scenario. In
      the United States, biologicals are widely used for moderate-to-severe psoriasis.
      But because of the high cost of medication and their availability in injection
      form, it remains to be seen how widely these agents will be utilized worldwide.
      Still, developing countries prefer conventional drugs.

PMID- 22463724
TI  - Differentiated thyroid carcinoma and intestinal polyposis syndromes.
AB  - Familial Adenomatous Polyposis, Cowden's Syndrome, and Peutz-Jeghers Syndrome are
      well known as Intestinal Polyposis Syndromes, inherited conditions characterized
      by the development of polyps of the gastro-intestinal tract in association with
      extra-intestinal manifestations, in particular malignant tumors at different
      sites. Thyroid carcinoma is sometimes a part of the clinical picture of these
      syndromes. The aim of this paper is to review the literature dealing with the
      association between differentiated thyroid carcinomas and Intestinal Polyposis
      Syndromes in order to point out peculiar aspects, providing suggestions for the
      screening and the management of thyroid tumors in these patients.

PMID- 22463725
TI  - Assessment of thymidylate synthase expression in biopsy specimens and
      corresponding resection specimens of non-small-cell lung cancer.
AB  - AIMS: Pemetrexed (Pem) is a potent inhibitor of thymidylate synthase (TS), and
      has shown efficacy in the treatment of non-small-cell lung cancer (NSCLC). TS
      expression in NSCLC biopsy specimens may correlate with the tumour responses to
      TS-inhibiting agents. As TS is not homogeneously expressed, our aim was to test
      whether TS expression in biopsy specimens may be representative for the whole
      tumour and can be used for therapeutic assessment. METHODS AND RESULTS: We
      immunohistochemically analysed TS expression in biopsy and corresponding
      resection specimens of 100 consecutive NSCLCs. The samples were subgrouped
      according to TS expression levels, and the degree of agreement between the biopsy
      and the corresponding resection specimen was calculated. TS expression-based
      grouping according to one cut-off criterion (high or low expression) led to
      concordant results between biopsy and resection specimens. When more than one cut
      off criterion was used, the results were significantly different. CONCLUSIONS:
      Thymidylate synthase expression levels in NSCLC biopsy specimens may correspond
      to TS expression of the whole tumour when robust scoring systems are applied.
      Further studies are needed to determine whether high or low TS expression in
      NSCLC biopsy specimens is of predictive value, and whether it may allow the
      selection of patients who will benefit from Pem treatment.

PMID- 22463727
TI  - Physical map and dynamics of the chaperone network in Escherichia coli.
AB  - Diverse families of molecular chaperones cooperate to effect protein homeostasis,
      but the extent and dynamics of direct interactions among chaperone systems within
      cells remain little studied. Here we used fluorescence resonance energy transfer
      to systematically map the network of pairwise interactions among the major
      Escherichia coli chaperones. We demonstrate that in most cases functional
      cooperation between chaperones within and across families involves physical
      complex formation, which pre-exists even in the absence of folding substrates.
      The observed connectivity of the overall chaperone network confirms its
      partitioning into sub-networks that are responsible for de novo protein folding
      and maturation and for refolding/disaggregation of misfolded proteins,
      respectively, and are linked by the Hsp70 system. We further followed heat
      induced changes in the cellular chaperone network, revealing two distinct
      pathways that process heat-denatured substrates. Our data suggest that protein
      folding within cells relies on highly ordered and direct channelling of
      substrates between chaperone systems and provide a comprehensive view of the
      underlying interactions and of their dynamics.

PMID- 22463726
TI  - Evolution of Bacillus thuringiensis Cry toxins insecticidal activity.
AB  - Insecticidal Cry proteins produced by Bacillus thuringiensis are use worldwide in
      transgenic crops for efficient pest control. Among the family of Cry toxins, the
      three domain Cry family is the better characterized regarding their natural
      evolution leading to a large number of Cry proteins with similar structure, mode
      of action but different insect specificity. Also, this group is the better
      characterized regarding the study of their mode of action and the molecular basis
      of insect specificity. In this review we discuss how Cry toxins have evolved
      insect specificity in nature and analyse several cases of improvement of Cry
      toxin action by genetic engineering, some of these examples are currently used in
      transgenic crops. We believe that the success in the improvement of insecticidal
      activity by genetic evolution of Cry toxins will depend on the knowledge of the
      rate-limiting steps of Cry toxicity in different insect pests, the mapping of the
      specificity binding regions in the Cry toxins, as well as the improvement of
      mutagenesis strategies and selection procedures.

PMID- 22463728
TI  - Remote participants' experiences with a group-based stroke self-management
      program using videoconference technology.
AB  - INTRODUCTION: Telehealth is an all-inclusive term for the provision of health
      services using information and communication technology. Videoconference delivery
      is one form of telehealth whereby a synchronous, two-way audio and visual
      connection is made between two or more sites. Videoconference is used in remote
      areas to improve access to healthcare, perform individual clinical assessments
      and deliver group education. Moving On after Stroke (MOST(r)) is a group-based,
      self-management program for stroke survivors and their caregivers, which consists
      of information sharing, facilitated discussion, goal-setting, and exercise. This
      program was delivered simultaneously to local participants onsite in Thunder Bay,
      Canada, and distant participants in smaller, remote communities in Northwestern
      Ontario using videoconferencing (MOST-Telehealth Remote). The objective of this
      study was to explore the experiences of remote participants, their perceptions
      regarding factors that enable or limit videoconference participation, and to
      obtain suggestions for enhanced delivery of videoconferenced group programs.
      METHODS: This qualitative study used an interpretive methodology. Semi-structured
      interviews were conducted in person with remote MOST-Telehealth Remote (MOST-TR)
      participants within one year post-program. Participants were recruited using
      purposive sampling and included both male and female stroke survivors and
      caregivers, those who participated alone and those who participated with others
      at the remote site. Twenty-seven people were approached, eight declined, and 19
      agreed to participate. The average age of participants was 66.2 years (range 48
      84). The interviews were transcribed and coded using NVivo v2.0
      (www.gsrinternational.com). Data were analyzed for common categories using
      qualitative descriptive methods. RESULTS: All participants valued access to the
      program without having to travel long distances. They felt safe in discussions
      and when exercising with the group across videoconference. Many reported 'feeling
      as if they were in the same room' but also acknowledged that there were
      limitations to participating via videoconference. Participants recognized a loss
      of subtleties in communication and the group facilitators found it difficult to
      discern whether participants were finding the exercises too difficult or too
      easy. The videoconference medium also limited participants' ability to privately
      or informally address concerns. Factors facilitating engagement and participation
      were similar to factors in face-to-face groups. Additionally, the importance of
      collaboration with onsite coordinators, volunteers, and other local participants
      was highlighted. Facilitators have the added responsibility of including all
      participants more explicitly, especially those offsite. Suggestions to improve
      group cohesion and participation included a preliminary face-to-face meeting with
      all participants, implementing technical strategies, and ongoing onsite support.
      CONCLUSIONS: For MOST-TR participants, videoconference participation was
      valuable. Addressing the limitations of videoconference connection and enhanced
      local support may improve the experience for remote participants in small-group,
      videoconferenced, self-management programs. Using videoconference technology to
      participate in existing programs greatly increases accessibility for people
      living in remote areas.

PMID- 22463729
TI  - Psychometric evaluation of a Dutch version of the Mini PAS-ADD for assessing
      psychiatric disorders in adults with different levels of intellectual disability.
AB  - BACKGROUND: People with intellectual disabilities (ID) have an increased
      vulnerability to develop psychiatric problems. Moreover, the early recognition
      and the accurate diagnosis of psychiatric disorders in the population of persons
      with ID are challenging. METHOD: A Dutch version of the Mini PAS-ADD, which is a
      screening instrument for identification of mental health problems in people with
      ID, was evaluated in terms of internal consistency, interinformant reliability,
      item grouping and criterion validity based on a large-scale random sample (n =
      377) and a clinical sample (n = 99) of adults with ID. RESULTS: The Dutch version
      of the Mini PAS-ADD showed moderate internal consistency, and moderate
      concordance among informants. Both aspects of the reliability were comparable for
      different levels of ID. A factor analysis largely confirmed the scale structure.
      Concurrent validity with the Reiss Screen for Maladaptive Behavior was high for
      the Depression, Psychosis and Autism scale. The outcome of the criterion-validity
      analysis indicated high specificity. The sensitivity for specific psychiatric
      disorders by the corresponding scales was moderate, but the general sensitivity
      for the presence of psychopathology on the basis of any of the scales was
      satisfying. CONCLUSIONS: The present research reconfirmed the use of the Mini PAS
      ADD as a primary screening device for the identification of mental health
      problems among people with ID.

PMID- 22463730
TI  - Anthelmintic and relaxant activities of Verbascum Thapsus Mullein.
AB  - BACKGROUND: Verbascum thapsus is used in tribal medicine as an antispasmodic,
      anti-tubercular agent and wormicide. In this study, we investigated the
      antispasmodic and anthelmintic activities of crude aqueous methanolic extract of
      the plant. METHODS: V. thapsus extracts were tested against roundworms (Ascaridia
      galli) and tapeworms (Raillietina spiralis). Each species of worm was placed into
      a negative control group, an albendazole treatment group, or a V. thapsus
      treatment group, and the time taken for paralysis and death was determined. In
      addition, relaxation activity tests were performed on sections of rabbit's
      jejunum. Plant extracts were tested on KCl-induced contractions and the
      relaxation activities were quantified against atropine. V. thapsus calcium
      chloride curves were constructed to investigate the mode of action of the plant
      extracts. RESULTS: We detected flavonoids, saponins, tannins, terpenoids,
      glycosides, carbohydrates, proteins, fats and fixed oils in V. thapsus. For both
      species of worm, paralysis occurred fastest at the highest concentration of
      extract. The relative index values for paralysis in A. galli were 4.58, 3.41 and
      2.08, at concentrations of 10, 20 and 40 mg/ml of plant extract, respectively.
      The relative index for death in A. galli suggested that V. thapsus extract is
      wormicidal at high concentration. Similarly, the relative indexes for paralysis
      and death in R. spiralis suggested that the extract is a more potent wormicidal
      agent than albendazole. The mean EC(50) relaxation activity values for
      spontaneous and KCl induced contractions were 7.5 +/- 1.4 mg/ml (6.57-8.01, n =
      6) and 7.9 +/- 0.41 mg/ml (7.44-8.46, n = 6), respectively. The relaxation
      activity of the extract was 11.42 +/- 2, 17.0 +/- 3, 28.5 +/- 4, and 128.0 +/- 7%
      of the maximum observed for atropine at corresponding concentrations. The calcium
      chloride curves showed that V. thapsus extracts (3 mg/ml), had a mean EC(50) (log
      molar [calcium]) value of -1.9 +/- 0.06 (-1.87 - -1.98, n = 6) vs. control EC(50)
      = -2.5 +/- 0.12 (-2.37 - -2.56, n = 6), whereas the verapamil (0.1 MUM) EC(50)
      was -1.7 +/- 0.1 (-1.6 - -1.8, n = 6) vs. control EC(50) = -2.4 +/- 0.09 (-2.3 - 
      2.47, n = 5). CONCLUSIONS: Our results suggest that V. thapsus, which is
      currently used by some tribes in the Malakand region of Pakistan, has
      anthelmintic and antispasmodic value.

PMID- 22463731
TI  - Mineralocorticoid receptor antagonist for renal protection.
AB  - The renin-angiotensin system (RAS) plays an important role in the pathophysiology
      of cardiovascular and renal diseases. In chronic kidney disease (CKD), blockade
      of RAS by angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor
      blocker (ARB) has been shown to reduce proteinuria and retard the progression of
      renal function deterioration. However, aldosterone, another key hormone of the
      RAS, is not directly targeted by ACEI or ARB. Hyperaldosteronism, apart from
      promoting sodium and fluid retention, causes inflammation and fibrosis in the
      heart and kidney. Studies have shown that although plasma aldosterone level shows
      an initial decrease following ACEI or ARB treatment, it returns to pretreatment
      level or even increases paradoxically after prolonged treatment. This
      "aldosterone breakthrough" forms the basis of adding mineralocorticoid receptor
      (MR) antagonist on top of ACEI or ARB for renal protection. New insights into the
      pathophysiological role of aldosterone in CKD further expands its potential
      indications, and there was a growing body of evidence in the past 10 years, which
      showed a substantial antiproteinuric effect and possibly a considerable
      renoprotective effect of MR antagonist. Since aldosterone does not act on the
      efferent glomerular arteriole and has no effect on intraglomerular hemodynamics,
      the very fact that MR antagonist ameliorates proteinuria sheds light on the
      physiology of glomerular permeability barrier. This review summarizes the data
      regarding the theoretical benefit as well as clinical use of MR antagonist in
      renal diseases.

PMID- 22463732
TI  - Proteomics analysis of differentially expressed proteins in chicken trachea and
      kidney after infection with the highly virulent and attenuated coronavirus
      infectious bronchitis virus in vivo.
AB  - BACKGROUND: Infectious bronchitis virus (IBV) is first to be discovered
      coronavirus which is probably endemic in all regions with intensive impact on
      poultry production. In this study, we used two-dimensional gel electrophoresis (2
      DE) and two-dimensional fluorescence difference gel electrophoresis (2-DIGE),
      coupled with matrix-assisted laser desorption/ionization time-of-flight tandem
      mass spectrometry (MALDI-TOF/TOF-MS), to explore the global proteome profiles of
      trachea and kidney tissues from chicken at different stages infected in vivo with
      the highly virulent ck/CH/LDL/97I P5 strain of infectious bronchitis virus (IBV)
      and the embryo-passaged, attenuated ck/CH/LDL/97I P115 strain. RESULTS: Fifty
      eight differentially expressed proteins were identified. Results demonstrated
      that some proteins which had functions in cytoskeleton organization, anti
      oxidative stress, and stress response, showed different change patterns in
      abundance from chicken infected with the highly virulent ck/CH/LDL/97I P5 strain
      and those given the embryo-passaged, attenuated P115 stain. In addition, the
      dynamic transcriptional alterations of 12 selected proteins were analyzed by the
      real-time RT-PCR, and western blot analysis confirmed the change in abundance of
      heat shock proteins (HSP) beta-1, annexin A2, and annexin A5. CONCLUSIONS: The
      proteomic alterations described here may suggest that these changes to protein
      expression correlate with IBV virus' virulence in chicken, hence provides
      valuable insights into the interactions of IBV with its host and may also assist
      with investigations of the pathogenesis of IBV and other coronavirus infections.

PMID- 22463733
TI  - Home medicines reviews following acute coronary syndrome: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Despite continual improvements in the management of acute coronary
      syndromes, adherence to guideline-based medications remains suboptimal. We aim to
      improve adherence with guideline-based therapy following acute coronary syndrome
      using an existing service that is provided by specifically trained pharmacists,
      called a Home Medicines Review. We have made two minor adjustments to target the
      focus of the existing service including an acute coronary syndrome specific
      referral letter and a training package for the pharmacists providing the service.
      METHODS/DESIGN: We will be conducting a randomized controlled trial to compare
      the directed home medicines review service to usual care following acute coronary
      syndromes. All patients aged 18 to 80 years and with a working diagnosis of acute
      coronary syndrome, who are admitted to two public, acute care hospitals, will be
      screened for enrolment into the trial. Exclusion criteria will include: not being
      discharged home, documented cognitive decline, non-Medicare eligibility, and
      presence of a terminal malignancy. Randomization concealment and sequence
      generation will occur through a centrally-monitored computer program. Patients
      randomized to the control group will receive usual post-discharge care. Patients
      randomized to receive the intervention will be offered usual post-discharge care
      and a directed home medicines review at two months post-discharge. The study
      endpoints will be six and twelve months post-discharge. The primary outcome will
      be the proportion of patients who are adherent to a complete, guideline-based
      medication regimen. Secondary outcomes will include hospital readmission rates,
      length of hospital stays, changes in quality of life, smoking cessation rates,
      cardiac rehabilitation completion rates, and mortality. DISCUSSION: As the trial
      is closely based on an existing service, any improvements observed should be
      highly translatable into regular practice. Possible limitations to the success of
      the trial intervention include general practitioner approval of the intervention,
      general practitioner acceptance of pharmacists' recommendations, and pharmacists'
      ability to make appropriate recommendations. A detailed monitoring process will
      detect any barriers to the success of the trial. Given that poor medication
      persistence following acute coronary syndrome is a worldwide problem, the
      findings of our study may have international implications for the care of this
      patient group. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry ACTRN12611000452998.

PMID- 22463734
TI  - Getting physicians to open the survey: little evidence that an envelope teaser
      increases response rates.
AB  - BACKGROUND: Physician surveys are an important tool to assess attitudes, beliefs
      and self-reported behaviors of this policy relevant group. In order for a
      physician to respond to a mailed survey, they must first open the envelope. While
      there is some evidence that package elements can impact physician response rates,
      the impact of an envelope teaser is unknown. Here we assess this by testing the
      impact of adding a brightly colored "$25 incentive" sticker to the outside of an
      envelope on response rates and nonresponse bias in a survey of physicians.
      METHODS: In the second mailing of a survey assessing physicians' moral beliefs
      and views on controversial health care topics, initial nonrespondents were
      randomly assigned to receive a survey in an envelope with a colored "$25
      incentive" sticker (teaser group) or an envelope without a sticker (control
      group). Response rates were compared between the teaser and control groups
      overall and by age, gender, region of the United States, specialty and years in
      practice. Nonresponse bias was assessed by comparing the demographic composition
      of the respondents to the nonrespondents in the experimental and control
      condition. RESULTS: No significant differences in response rates were observed
      between the experimental and control conditions overall (p = 0.38) or after
      stratifying by age, gender, region, or practice type. Within the teaser
      condition, there was some variation in response rate by years since graduation.
      There was no independent effect of the teaser on response when simultaneously
      controlling for demographic characteristics (OR = 0.875, p = 0.4112).
      CONCLUSIONS: Neither response rates nor nonresponse bias were impacted by the use
      of an envelope teaser in a survey of physicians in the United States.

PMID- 22463735
TI  - Behavioural responses of Anopheles gambiae sensu stricto M and S molecular form
      larvae to an aquatic predator in Burkina Faso.
AB  - BACKGROUND: Predation of aquatic immature stages has been identified as a major
      evolutionary force driving habitat segregation and niche partitioning in the
      malaria mosquito Anopheles gambiae sensu stricto in the humid savannahs of
      Burkina Faso, West Africa. Here, we explored behavioural responses to the
      presence of a predator in wild populations of the M and S molecular forms of An.
      gambiae that typically breed in permanent (e.g., rice field paddies) and
      temporary (e.g., road ruts) water collections. METHODS: Larvae used in these
      experiments were obtained from eggs laid by wild female An. gambiae collected
      from two localities in south-western Burkina Faso during the 2008 rainy season.
      Single larvae were observed in an experimental arena, and behavioural traits were
      recorded and quantified a) in the absence of a predator and b) in the presence of
      a widespread mosquito predator, the backswimmer Anisops jaczewskii. Differences
      in the proportion of time allocated to each behaviour were assessed using
      Principal Component Analysis and Multivariate Analysis of Variance. RESULTS: The
      behaviour of M and S form larvae was found to differ significantly; although both
      forms mainly foraged at the water surface, spending 60-90% of their time
      filtering water at the surface or along the wall of the container, M form larvae
      spent on average significantly more time browsing at the bottom of the container
      than S form larvae (4.5 vs. 1.3% of their overall time, respectively; P < 0.05).
      In the presence of a predator, larvae of both forms modified their behaviour,
      spending significantly more time resting along the container wall (P < 0.001).
      This change in behaviour was at least twice as great in the M form (from 38.6 to
      66.6% of the time at the wall in the absence and presence of the predator,
      respectively) than in the S form (from 48.3 to 64.1%). Thrashing at the water
      surface exposed larvae to a significantly greater risk of predation by the
      notonectid (P < 0.01), whereas predation occurred significantly less often when
      larvae were at the container wall (P < 0.05) and might reflect predator
      vigilance. CONCLUSIONS: Behavioural differences between larvae of the M and S
      form of An. gambiae in response to an acute predation risk is likely to be a
      reflection of different trade-offs between foraging and predator vigilance that
      might be of adaptive value in contrasting aquatic ecosystems. Future studies
      should explore the relevance of these findings under the wide range of natural
      settings where both forms co-exist in Africa.

PMID- 22463736
TI  - Highly regioselective synthesis of 1,3-diiodonaphthalene derivatives via a
      sequential cascade iodocyclization.
AB  - A novel and flexible sequentially cascade iodocyclization for the synthesis of
      highly substituted 1,3-diiodinated naphthalene derivatives in up to 99% yield
      under mild conditions is reported. The dihalogenated moiety can be readily
      introduced into the naphthalenes in a position that is usually not easily
      functionalized.

PMID- 22463737
TI  - Janus kinase inhibition and its effect upon the therapeutic landscape for
      myelofibrosis: from palliation to cure?
AB  - Following the discovery of the Janus kinase (JAK) 2 V617F mutation in 2005 the
      explosion of research and drug development activity has not only advanced our
      understanding of the pathogenesis of myeloproliferative neoplasms (MPNs) but also
      triggered debate about classification, allowed revised diagnostic and response
      criteria, provided a target for treatment and a mode of monitoring its success.
      These changes and the resultant clinical research are discussed in this article
      where we argue that discovery of the JAK2 V617F mutation has signalled the much
      delayed change in therapeutic paradigm for myelofibrosis and possibly other MPNs
      from palliation and allowing us to move closer to, but not yet attain, a cure.

PMID- 22463738
TI  - Insight into trade-off between wood decay and parasitism from the genome of a
      fungal forest pathogen.
AB  - Parasitism and saprotrophic wood decay are two fungal strategies fundamental for
      succession and nutrient cycling in forest ecosystems. An opportunity to assess
      the trade-off between these strategies is provided by the forest pathogen and
      wood decayer Heterobasidion annosum sensu lato. We report the annotated genome
      sequence and transcript profiling, as well as the quantitative trait loci
      mapping, of one member of the species complex: H. irregulare. Quantitative trait
      loci critical for pathogenicity, and rich in transposable elements, orphan and
      secreted genes, were identified. A wide range of cellulose-degrading enzymes are
      expressed during wood decay. By contrast, pathogenic interaction between H.
      irregulare and pine engages fewer carbohydrate-active enzymes, but involves an
      increase in pectinolytic enzymes, transcription modules for oxidative stress and
      secondary metabolite production. Our results show a trade-off in terms of
      constrained carbohydrate decomposition and membrane transport capacity during
      interaction with living hosts. Our findings establish that saprotrophic wood
      decay and necrotrophic parasitism involve two distinct, yet overlapping,
      processes.

PMID- 22463739
TI  - The impact of hepatic portoenterostomy on liver transplantation for the treatment
      of biliary atresia: early failure adversely affects outcome.
AB  - The most common indication for pediatric LTx is biliary atresia with failed HPE,
      yet the effect of previous HPE on the outcome after LTx has not been well
      characterized. We retrospectively reviewed a single-center experience with 134
      consecutive pediatric liver transplants for the treatment of biliary atresia from
      1 May 1995 to 28 April 2008. Of 134 patients, 22 underwent LTx without prior HPE
      (NPE), while 112 patients underwent HPE first. HPE patients were grouped into EF,
      defined as need for LTx within the first year of life, and LF, defined as need
      for LTx beyond the first year of life. NPE and EF groups differed significantly
      from the LF group in age, weight, PELD, and ICU status (p < 0.05) with NPE having
      the highest PELD and ICU status. Patients who underwent salvage LTx after EF
      following HPE had a significantly higher incidence of post-operative bacteremia
      and septicemia (p < 0.05), and subsequently lower survival rates. One-year
      patient survival and graft survival were as follows: NPE 100%, EF 81%, and LF 96%
      (p < 0.05); and NPE 96%, EF 79%, and LF 96% (p < 0.05). Further investigation
      into the optimal treatment of biliary atresia should focus on identifying
      patients at high risk of EF who may benefit from proceeding directly to LTx given
      the increased risk of post-LTx bacteremia, sepsis, and death after failed HPE.

PMID- 22463740
TI  - The role of stem cells in muscular dystrophies.
AB  - Muscular dystrophies are heterogeneous neuromuscular disorders of inherited
      origin, including Duchenne muscular dystrophy (DMD). Cell-based therapies were
      used to promote muscle regeneration with the hope that the host cells repopulated
      the muscle and improved muscle function and pathology. Stem cells were preferable
      for therapeutic applications, due to their capacity of self-renewal and
      differentiative potential. In the last years, encouraging results were obtained
      with adult stem cells to treat muscular dystrophies. Adult stem cells were found
      into various tissues of the body and they were able to maintain, generate, and
      replace terminally differentiated cells within their own specific tissue because
      of cell turnover or tissue injury. Moreover, it became clear that these cells
      could participate into regeneration of more than just their resident organ. Here,
      we described multiple types of muscle and non muscle-derived myogenic stem cells,
      their characterization and their possible use to treat muscular dystrophies. We
      also underlined that most promising possibility for the management and therapy of
      DMD is a combination of different approaches, such as gene and stem cell therapy.

PMID- 22463741
TI  - An investigation of horizontal transfer of feed introduced DNA to the aerobic
      microbiota of the gastrointestinal tract of rats.
AB  - BACKGROUND: Horizontal gene transfer through natural transformation of members of
      the microbiota of the lower gastrointestinal tract (GIT) of mammals has not yet
      been described. Insufficient DNA sequence similarity for homologous recombination
      to occur has been identified as the major barrier to interspecies transfer of
      chromosomal DNA in bacteria. In this study we determined if regions of high DNA
      similarity between the genomes of the indigenous bacteria in the GIT of rats and
      feed introduced DNA could lead to homologous recombination and acquisition of
      antibiotic resistance genes. RESULTS: Plasmid DNA with two resistance genes (nptI
      and aadA) and regions of high DNA similarity to 16S rRNA and 23S rRNA genes
      present in a broad range of bacterial species present in the GIT, were
      constructed and added to standard rat feed. Six rats, with a normal microbiota,
      were fed DNA containing pellets daily over four days before sampling of the
      microbiota from the different GI compartments (stomach, small intestine, cecum
      and colon). In addition, two rats were included as negative controls. Antibiotic
      resistant colonies growing on selective media were screened for recombination
      with feed introduced DNA by PCR targeting unique sites in the putatively
      recombined regions. No transformants were identified among 441 tested isolates.
      CONCLUSIONS: The analyses showed that extensive ingestion of DNA (100 MUg
      plasmid) per day did not lead to increased proportions of kanamycin resistant
      bacteria, nor did it produce detectable transformants among the aerobic
      microbiota examined for 6 rats (detection limit < 1 transformant per 1,1 * 10(8)
      cultured bacteria). The key methodological challenges to HGT detection in animal
      feedings trials are identified and discussed. This study is consistent with other
      studies suggesting natural transformation is not detectable in the GIT of
      mammals.

PMID- 22463742
TI  - Pentoxifylline reduces tumor necrosis factor-alpha and HIV-induced vascular
      endothelial activation.
AB  - Untreated HIV infection is associated with endothelial dysfunction and subsequent
      cardiovascular disease, likely due to both direct effects of the virus and to
      indirect effects of systemic inflammation on the vasculature. We have recently
      shown that treatment with the antiinflammatory agent pentoxifylline (PTX)
      improved in vivo endothelial function and reduced circulating levels of the
      inflammatory markers vascular cell adhesion molecule-1 (VCAM-1) and interferon
      gamma-induced protein (IP-10) in HIV-infected patients. To delineate the
      mechanisms underlying this therapeutic effect, we tested whether clinically
      relevant concentrations of PTX suppress VCAM-1 or IP-10 release in cultivated
      human lung microvascular endothelial cells. Indeed, we found that tumor necrosis
      factor (TNF)-alpha-induced VCAM-1 was reduced with concentrations of PTX in the
      low nanomolar range, comparable to plasma levels in PTX-treated groups. We also
      investigated the effect of HIV proteins and found that HIV transactivator of
      transcription (HIV-Tat) and HIV-envelope-derived recombinant gp120 enhanced TNF
      alpha-induced VCAM-1 gene expression in lung microvascular and coronary
      macrovascular endothelial cells, respectively. In addition, PTX and a NF-kappaB
      specific inhibitor reduced this enhanced VCAM-1 gene induction in microvascular
      and macrovascular endothelial cells. These results provide novel insights in how
      the antiinflammatory agent PTX can directly reduce HIV-associated proinflammatory
      endothelial activation, which may underlie vascular dysfunction and coronary
      vascular diseases.

PMID- 22463743
TI  - Roles of human urotensin II in volume resistance hypertension in peritoneal
      dialysis patients.
AB  - Human urotensin II (hUII) is a newly discovered substance that can dilate small
      blood vessels to decrease the blood pressure (BP). Our previous studies showed
      that some volume-overloaded patients on peritoneal dialysis can maintain normal
      BP (congestive heart failure excluded), suggesting that these patients have
      volume resistance capacity. This study is to investigate whether hUII plays an
      important role in this subgroup of patients on peritoneal dialysis. In this
      study, 105 patients on continuous ambulatory peritoneal dialysis were enrolled.
      Volume load was evaluated by the overhydration (OH) value obtained by
      bioimpedance analysis. OH < 2.0 kg was defined as normal volume (NV), and OH >=
      2.0 kg as high volume (HV). Systolic blood pressure (SBP) <130 mmHg was defined
      as normotension (NT) and >=130 mmHg as hypertension (HT). The patients were thus
      divided into four subgroups: (1) normotension with normal volume (NT-NV), (2)
      normotension with high volume (NT-HV), (3) normal volume with hypertension (HT
      NV), and (4) high volume with hypertension (HT-HV). hUII was measured using
      radioimmunoassay method. hUII was significantly higher in normal SBP group than
      that in high SBP group (p < 0.05). hUII was higher in the NT-HV group compared
      with that in the HT-HV group (p < 0.05). Our study suggests that hUII may be
      involved in the pathogenesis of the volume resistance HT in peritoneal dialysis
      patients.

PMID- 22463744
TI  - Piperine, a component of black pepper, inhibits adipogenesis by antagonizing
      PPARgamma activity in 3T3-L1 cells.
AB  - This study investigated the antiadipogenic activity of black pepper extract and
      its constituent piperine in 3T3-L1 preadipocytes as well as the underlying
      molecular mechanisms. Both black pepper extract and piperine, without affecting
      cytotoxicity, strongly inhibited the adipocyte differentiation of 3T3-L1 cells.
      The mRNA expression of the master adipogenic transcription factors, PPARgamma,
      SREBP-1c, and C/EBPbeta, was markedly decreased. Intriguingly, mRNA levels of
      PPARgamma target genes were also down-regulated. Moreover, a luciferase reporter
      assay indicated that pipierine significantly represses the rosiglitazone-induced
      PPARgamma transcriptional activity. Finally, GST-pull down assays demonstrated
      that piperine disrupts the rosiglitazone-dependent interaction between PPARgamma
      and coactivator CBP. Genome-wide analysis using microarray further supports the
      role of piperine in regulating genes associated with lipid metabolism. Overall,
      these results suggest that piperine, a major component of black pepper,
      attenuates fat cell differentiation by down-regulating PPARgamma activity as well
      as suppressing PPARgamma expression, thus leading to potential treatment for
      obesity-related diseases.

PMID- 22463746
TI  - Stage II colonic adenocarcinoma: a detailed study of pT4N0 with emphasis on
      peritoneal involvement and the role of tumour budding.
AB  - AIMS: Evaluation of peritoneal involvement in colonic cancer (CC) can be
      difficult. We studied pT4N0 cancers and their association with pathological
      prognostic markers, including tumour budding. METHOD AND RESULTS: Tumours were
      classified as (i) at the peritoneal surface or free in the peritoneal cavity
      (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n =
      8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n
      = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard
      pathological markers including tumour budding were assessed. Elastin staining was
      performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion
      criteria. There was no significant difference in survival across subgroups. pT4b
      tumours were larger than pT4a tumours (P < 0.001). Over-represented features in
      pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin
      (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis,
      neural invasion was the only parameter predictive of survival (hazard ratio =
      2.8; 95% CI 1.2-6.4; P = 0.02). CONCLUSION: Stage II pT4I CCs have a similar
      outcome to T4a/b tumours. Elastin staining is useful in defining this group.
      Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not
      predict outcome in pT4N0 disease. Only neural invasion independently predicted
      poor outcome.

PMID- 22463745
TI  - Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin
      4.5% polymer matrix collar (Seresto(r)) in dogs and cats naturally infested with
      fleas and/or ticks in multicentre clinical field studies in Europe.
AB  - BACKGROUND: The objective of these two GCP multicentre European clinical field
      studies was to evaluate the long-term efficacy and safety of a new
      imidacloprid/flumethrin collar (Seresto(r), Bayer AnimalHealth, Investigational
      Veterinary Product(IVP)) in dogs and cats naturally infested with fleas and/or
      ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer
      Katzen", Beaphar, Control Product (CP)). METHODS: 232 (IVP) and 81 (CP) cats and
      271(IVP) and 129 (CP) dogs were treated with either product according to label
      claims and formed the safety population. Flea and tick counts were conducted in
      monthly intervals for up to 8 months in the efficacy subpopulation consisting of
      118 (IVP) + 47 (CP) cats and 197 (IVP) + 94 (CP) dogs. Efficacy was calculated as
      reduction of infestation rate within the same treatment group and statistically
      compared between the two treatment groups. RESULTS: Preventive efficacy against
      fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100%
      (overall mean: 98.3%/96.7%) throughout the 8 month period and in the CP group
      between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%). Preventive
      efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2%
      and 100%/100% (overall mean: 98.4%/94.7%) throughout the 8 month period and in
      the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%). The
      IVP group was statistically non-inferior to the CP group, and on various
      assessment days, statistical superiority was proven for flea and tick count
      reduction in dogs and cats. Both treatments proved to be safe in dogs and cats
      with mainly minor local observations at the application site. There was moreover,
      no incidence of any mechanical problem with the collar in dogs and cats during
      the entire study period. CONCLUSIONS: The imidacloprid/flumethrin collar proved
      to reduce tick counts by at least 90% and flea counts by at least 95% for a
      period of at least 7-8 months in cats and dogs under field conditions. Therefore,
      it can be used as sustainable long-term preventative, covering the whole flea and
      tick season.

PMID- 22463748
TI  - [Florence Nightingale and the Risorgimento:  her way of  thinking through her
      correspondence, 1837- 1872].
AB  - Florence Nightingale was a great admirer of our country. She deeply loved the
      Italian culture, as demonstrated by her repeated trips in our country and her
      knowledge of the language and the ancient Roman's culture. The analysis of her
      letters concerning her journeys in Italy  are very interesting because you can
      find reviews, descriptions and confirmation of her involvement in our
      Risorgimento, in terms of shared values and support the cause. The correspondence
      gives an overview of feeling and actions that it shows a sense of justice and
      freedom, feelings that led to a real participation, although the economic and
      intellectual, to the cause of the Italians insurgents. The evolution of these
      values in her life paint a less known side of the thoughts of Florence
      Nightingale, founder of the nursing profession, but also advocate for universal
      human rights. Even in this case, she shows the strength of character that has
      marked much of her work, exposing herself in support of the Risorgimento.

PMID- 22463747
TI  - miR-15a and 16-1 are downregulated in CD4+ T cells of multiple sclerosis
      relapsing patients.
AB  - The pathology of relapsing-remitting multiple sclerosis (RR-MS) is largely
      attributed to activated autoreactive effector T lymphocytes. The influence of
      microRNAs on the immune response has been shown to occur in different pathways of
      lymphocyte differentiation and function. Here, the expression of the miRNAs miR
      15a/16-1 in PBMC, CD4(+), and CD8(+) from RR-MS patients has been investigated.
      BCL2, a known miR-15a/16-1 target, has also been analyzed. The results have shown
      that miR-15a/16-1 is downregulated in CD4(+) T cells, whereas BCL2 is highly
      expressed in RR-MS patients only. Our data suggest that miR-15a/16-1 can also
      modulate the BCL2 gene expression in CD4(+) T cells from RR-MS patients, thereby
      affecting apoptosis processes.

PMID- 22463749
TI  - ["The grandest hero who has ever lived": an unpublished letter written by
      Florence Nightingale about Garibaldi].
AB  - In  the year of the 150th anniversary of the Unity of Italy, Italian nurses
      cannot forget that Florence Nightingale herself, founder of modern Nursing , was
      a fervid support of the Risorgimento and of Italian unity.  An unpublished
      letter, signed by her and conserved in the State archives of Pistoia, illustrates
      her feelings about  the process of unity under way  in the country where she was
      born.

PMID- 22463751
TI  - [Comparative analysis of methods finalized at defining the need for nursing
      staff. Evaluation of work loads].
AB  - Due to demographic and technological changes , medical progress and increased
      demand, nursing work-loads are changing. The aim of this study is to observe
      which methods exist in other countries to assess the need for nursing staff. The
      results obtained show that the choice of the method for evaluating nursing
      requirements is strongly influenced by the health economy policy adopted in each
      single country and by the type of care erogated by the health institution
      considered.

PMID- 22463750
TI  - [Nursing Research Project on Management Training (IN.FOR.MA): evaluation of the
      competencies acquired during Phase 1].
AB  - The aim of the present study is to define the state of the art in nursing
      management training in Italy and to assess the effectiveness of training in a
      working context. The first phase of the  IN.FOR.MA project consisted of creating
      a data collection tool, a questionnaire, based on paradigmatic  pedagogic
      methodology. This was followed by a pilot study to test its effectiveness.
      Reliability was tested  using the Cronbach's alpha test  and the values obtained
      were between 0.79 and 0.82 for the overall scale and between 0.71  and 0.90 for
      the subscales. The maximum expression of the competencies perceived using the
      Likert scale was 4 (Fair), with a maximum value of 5 obtained in 53,06% of the
      total sample in the "Management" area  and a minimum value between 3 (discreet)
      and 4 (fair) in 33.6% of the total in the area "Training and Research".
      Perception of the working value of the training experience reached 5 (very) ,
      with an average value of  54,08% of the overall sample. The IN.FOR.MA
      questionnaire made it possible to assess the training course by focusing on the
      perception of the competencies acquired, with medium to high levels according to
      the Likert scale. The level of usefulness of these competencies in daily
      activities was highest in "Management" followed by "Programming and organization"
      and "Integration".

PMID- 22463752
TI  - [The measurement of individualized care: translation and validation semantics  of
      Individualized Care Scale].
AB  - The aim of this study was to translate into Italian , with semantic validation,
      the Individualized Care Scale  and to provide some indications for using it in an
      Italian cultural and professional context , to improve its effectiveness as an
      indicator of the level of nursing care in Italy. This was done using a double
      forward blind parallel translation by specialized translators followed by
      evauation of the translations by a panel of experts (so-called Committee
      approach). The cultural validity of the ICS was then tested. The translation of
      the ICS obtained by our study group proved to be comprehensible and easily
      applied in an Italian cultural and professional context, making it  an effective
      tool for assessing the opinions of patients regarding the care received. Results
      confirmed the  usefulness of this tool for evaluating personalized care but
      further studies are necessary using statistical verification, to draw definite
      conclusions  regarding the Italian version.

PMID- 22463753
TI  - [Post-traumatic stress disorder in the Ares 118 voluntary ambulance staff in the
      Latina area: preliminary study to validate the PTSS-10].
AB  - The study investigates and describes post-traumatic stress testing for the
      Italian validation of the abbreviated form of the Scale for the Symptoms of Post
      Traumatic Stress Disorder (PTSS-10). It's a scale comprising 10 items and the
      article takes into consideration the German version, derived from the original
      Norwegian. The scale is based on the concept of multidirectional stress supported
      by Lazarus. Its validation and testing was conducted on a group of 60 ARES 118
      volunteers of Latina. The study reports the internal reliability of the
      translated instrument, calculated using Cronbach's alpha and compared to German
      study. 'Factor Analysis is calculated and the results are discussed. Some
      remarks, also, are made by relating scores indicating a suspected PTSD with socio
      demographic variables. The results demonstrate the reliability of the instrument,
      but for a generalization, it should be tested on a larger sample and apply the
      test -retest.

PMID- 22463754
TI  - Examination of the phases of metasynthesis: a study on patients' duties as an
      example.
AB  - In recent years, the use of metasynthesis as a research method has increased
      within nursing science. In the present paper, we focus on examining the phases of
      metasynthesis, using a study of patients' duties as an example. The aim of this
      paper is to increase the understanding of synthesis as a method in order to
      promote research trustworthiness by making the research process more transparent
      and thereby increasing the readers' awareness of it. We formulated a purpose for
      each phase of metasynthesis in order to better understand synthesis as a rational
      thinking process. We found that the collaboration of several researchers during
      all phases of metasynthesis is needed in order to maintain research ethics and
      trustworthiness. In addition, further study of the phases of metasynthesis is
      needed for improving research methods in order to produce new, accumulated
      knowledge based on previous qualitative study.

PMID- 22463755
TI  - Symptomatic delayed trans-dural herniation and strangulation of cauda equinae
      following resection of Myxopapillary ependymoma.
AB  - Pseudomeningocoele is a recognised complication of spinal surgery. It could be
      either asymptomatic or symptomatic. We present a 63-year-old male who developed a
      delayed pseudomeningocoele and symptomatic transdural herniation and
      strangulation of the cauda equinae following resection of a Myxopapillary
      ependymoma. He underwent successful operative re-exploration, un-tethering of the
      cauda equinae and re-closure of the dural defect with resolution of his symptoms.
      We discuss the clinical features, operative technical factors involved and the
      essential importance of neuroimaging with critical analysis of the imaging
      findings and correlation of the clinical symptoms, when such a diagnosis is being
      considered.

PMID- 22463756
TI  - Advanced thermal hydrolysis: optimization of a novel thermochemical process to
      aid sewage sludge treatment.
AB  - The aim of this work was to study in depth the behavior and optimization of a
      novel process, called advanced thermal hydrolysis (ATH), to determine its utility
      as a pretreatment (sludge solubilization) or postreatment (organic matter
      removal) for anaerobic digestion (AD) in the sludge line of wastewater treatment
      plants (WWTPs). ATH is based on a thermal hydrolysis (TH) process plus hydrogen
      peroxide (H(2)O(2)) addition and takes advantage of a peroxidation/direct steam
      injection synergistic effect. On the basis of the response surface methodology
      (RSM) and a modified Doehlert design, an empirical second-order polynomial model
      was developed for the total yield of: (a) disintegration degree [DD (%)]
      (solubilization), (b) filtration constant [F(c) (cm(2)/min)] (dewaterability),
      and (c) organic matter removal (%). The variables considered were operation time
      (t), temperature reached after initial heating (T), and oxidant coefficient (n =
      oxygen(supplied)/oxygen(stoichiometric)). As the model predicts, in the case of
      the ATH process with high levels of oxidant, it is possible to achieve an organic
      matter removal of up to 92%, but the conditions required are prohibitive on an
      industrial scale. ATH operated at optimal conditions (oxygen amount 30% of
      stoichiometric, 115  degrees C and 24 min) gave promising results as a
      pretreatment, with similar solubilization and markedly better dewaterability
      levels in comparison to those obtained with TH at 170  degrees C. The empirical
      validation of the model was satisfactory.

PMID- 22463757
TI  - Acceptance of technology-enhanced learning for a theoretical radiological science
      course: a randomized controlled trial.
AB  - BACKGROUND: Technology-enhanced learning (TEL) gives a view to improved
      education. However, there is a need to clarify how TEL can be used effectively.
      The study compared students' attitudes and opinions towards a traditional face-to
      face course on theoretical radiological science and a TEL course where students
      could combine face-to-face lectures and e-learning modules at their best
      convenience. METHODS: 42 third-year dental students were randomly assigned to the
      traditional face-to-face group and the TEL group. Both groups completed
      questionnaires before the beginning and after completion of the course on
      attitudes and opinions towards a traditional face-to-face lectures and technology
      enhanced learning. After completion of the course both groups also filled in the
      validated German-language TRIL (Trierer Inventar zur Lehrevaluation)
      questionnaire for the evaluation of courses given at universities. RESULTS: Both
      groups had a positive attitude towards e-learning that did not change over time.
      The TEL group attended significantly less face-to-face lectures than the
      traditional group. However, both groups stated that face-to-face lectures were
      the basis for education in a theoretical radiological science course. The members
      of the TEL group rated e-mail reminders significantly more important when they
      filled in the questionnaire on attitudes and opinions towards a traditional face
      to-face lectures and technology-enhanced learning for the second time after
      completion of the course. The members of the technology-enhanced learning group
      were significantly less confident in passing the exam compared to the members of
      the traditional group. However, examination results did not differ significantly
      for traditional and the TEL group. CONCLUSIONS: It seems that technology-enhanced
      learning in a theoretical radiological science course has the potential to reduce
      the need for face-to-face lectures. At the same time examination results are not
      impaired. However, technology-enhanced learning cannot completely replace
      traditional face-to-face lectures, because students indicate that they consider
      traditional teaching as the basis of their education.

PMID- 22463758
TI  - Human bone marrow stromal cells simultaneously support B and T/NK lineage
      development from human haematopoietic progenitors: a principal role for flt3
      ligand in lymphopoiesis.
AB  - The regulation of human early lymphopoiesis remains unclear. B- and T-lineage
      cells cannot develop simultaneously with conventional stromal cultures. Here we
      show that telomerized human bone marrow stromal cells supported simultaneous
      generation of CD19(+) CD34(lo/-) CD10(+) cyCD79a(+) CD20(+/-) VpreB(-)  pro-B
      cells and CD7(+) CD34(+)  CD45RA(+) CD56(-) cyCD3(-)  early T/Natural Killer (NK)
      cell precursors from human haematopoietic progenitors, and the generation of both
      lymphoid precursors was promoted by flt3 ligand (flt3L). On the other hand, stem
      cell factor or thrombopoietin had little or no effect when used alone. However,
      both acted synergistically with flt3L to augment the generation of both lymphoid
      precursors. Characteristics of these lymphoid precursors were evaluated by gene
      expression profiles, rearrangements of IgH genes, or replating assays. Similar
      findings were observed with primary human bone marrow stromal cells. Notably,
      these two lymphoid-lineage precursors were generated without direct contact with
      stromal cells, indicating that early B and T/NK development can occur, at least
      in part, by stromal cell-derived humoral factors. In serum-free cultures, flt3L
      elicited similar effects and appeared particularly important for B cell
      development. The findings of this study identified the potential of human bone
      marrow stromal cells to support human early B and T lymphopoiesis and a principal
      role for flt3L during early lymphopoiesis.

PMID- 22463759
TI  - Kinetic mechanism of initiation by RepD as a part of asymmetric, rolling circle
      plasmid unwinding.
AB  - Some bacterial plasmids carry antibiotic resistance genes and replicate by an
      asymmetric, rolling circle mechanism, in which replication of the two strands is
      not concurrent. Initiation of this replication occurs via an initiator protein
      that nicks one DNA strand at the double-stranded origin of replication. In this
      work, RepD protein from the staphylococcal plasmid pC221 carries this function
      and allows PcrA helicase to bind and begin unwinding the plasmid DNA. This work
      uses whole plasmid constructs as well as oligonucleotide-based mimics of parts of
      the origin to examine the initiation reaction. It investigates the phenomenon
      that nicking, although required to open a single-stranded region at the origin
      and so allow PcrA to bind, is not required for another function of RepD, namely
      to increase the processivity of PcrA, allowing it to unwind plasmid lengths of
      DNA. A kinetic mechanism of RepD initiation is presented, showing rapid binding
      of the origin DNA. The rate of nicking varies with the structure of the DNA but
      can occur with a rate constant of >25 s(-1) at 30  degrees C. The equilibrium
      constant of the nicking reaction, which involves a transesterification to form a
      phosphotyrosine bond within the RepD active site, is close to unity.

PMID- 22463760
TI  - Isolation and characterization of microsatellite loci for the Potentilla core
      group (Rosaceae) using 454 sequencing.
AB  - Microsatellites are valuable markers for the analysis of genetic diversity,
      linkage mapping or genotyping. The limited availability of microsatellites for
      the genus Potentilla (Rosaceae) stipulated the isolation of markers from a
      representative (Potentilla pusilla Host) of the Potentilla core group that
      constitutes the most species-rich evolutionary lineage within the genus. Thousand
      four hundred and seventy-six simple sequence repeat (SSR) containing candidate
      sequences were isolated from a single-type line using 454 sequencing. Seventy
      four functional microsatellite markers were developed from 200 sequences selected
      for suitable priming sites flanking microsatellite repeats referring to a 37%
      primer-to-marker conversion ratio. Seventy-two markers were polymorphic. These
      numbers confirm the increased efficiency of pyrosequencing over traditional
      isolation techniques in the development of microsatellites. Amplification primer
      sequences and the sequences of corresponding target fragments are provided for
      all functional markers, and molecular polymorphisms estimated for four accessions
      of P. pusilla and among seven core group species represented by 14 individuals
      are reported. Cross-species transferability ranged between 86.4% and 97.3% among
      the studied taxa, and 57, 11 and six of the selected primer pairs amplified
      fragments of expected size and number in seven, six and five of the species,
      respectively. Reproducibility of the molecular phenotypes was 97.0%, which was
      inferred using a replicate sample of P. pusilla.

PMID- 22463762
TI  - The associations between feeding difficulties and behaviours and dietary patterns
      at 2 years of age: the ALSPAC cohort.
AB  - Little is known about the dietary patterns of toddlers. This period of life is
      important for forming good dietary habits later in life. Using dietary data
      collected via food frequency questionnaire (FFQ) at 2 years of age, we examined
      the dietary patterns of children from the Avon Longitudinal Study of Parents and
      Children (ALSPAC). Principal component analysis was performed for 9599 children
      and three patterns were extracted: 'family foods' associated with traditional
      British family foods such as meat, fish, puddings, potatoes and vegetables;
      'sweet and easy' associated with foods high in sugar (sweets, chocolate, fizzy
      drinks, flavoured milks) and foods requiring little preparation (crisps,
      potatoes, baked beans, peas, soup); 'health conscious' associated with fruit,
      vegetables, eggs, nuts and juices. We found clear associations between dietary
      pattern scores and socio-demographic variables, with maternal education being the
      most important. Higher levels of education were associated with higher scores on
      both the 'family foods' and the 'health conscious' patterns, and decreased scores
      on the 'sweet and easy' pattern. Relationships were evident between dietary
      pattern scores and various feeding difficulties and behaviours. Notably, children
      who were introduced late to lumpy (chewy) solids (after 9 months) scored lower on
      both the 'family foods' and the 'health conscious' patterns. Further analyses are
      required to determine the temporal relationship between perceived feeding
      difficulties and behaviours, and it will be important to assess the contribution
      of the age of introduction to lumpy solids to these relationships. 

PMID- 22463761
TI  - Role of a Candida albicans Nrm1/Whi5 homologue in cell cycle gene expression and
      DNA replication stress response.
AB  - To explore cell cycle regulation in the dimorphic fungus Candida albicans, we
      identified and characterized CaNrm1, a C. albicans homologue of the Saccharomyces
      cerevisiae Whi5 and Nrm1 transcription inhibitors that, analogous to mammalian
      Rb, regulate the cell cycle transcription programme during the G1 phase. CaNRM1
      is able to complement the phenotypes of both whi5 and nrm1 mutants in S.
      cerevisiae. In C. albicans, global transcription analysis of the CaNRM1 deletion
      mutant reveals a preferential induction of G1- and G1/S-specific genes. CaNrm1
      interacts genetically with the C. albicans MBF functional homologue, and
      physically with its subunit CaSwi4. Similar to S. cerevisiae Whi5, CaNrm1
      subcellular localization oscillates with the cell cycle between the nucleus and
      the cytoplasm. Deletion of CaNRM1 further results in increased resistance to
      hydroxyurea, an inhibitor of DNA replication; analysis of the expression of
      ribonucleotide reductase, the target of hydroxyurea, suggests that its
      transcriptional induction in response to hydroxyurea is regulated via CaNrm1, and
      biochemical analysis shows that hydroxyurea causes disruption of the interaction
      of CaNrm1 with CaSwi4. Furthermore, induction of the hyphal-specific genes is
      dampened under certain conditions in the Canrm1(-/-) mutant, suggesting that the
      cell cycle transcription programme can influence the morphogenetic transcription
      programme of C. albicans.

PMID- 22463763
TI  - Primary care for adults with Down syndrome: adherence to preventive healthcare
      recommendations.
AB  - BACKGROUND: Due to significant medical improvements, persons with Down syndrome
      now live well into adulthood. Consequently, primary care for adults with Down
      syndrome needs to incorporate routine care with screening for condition-specific
      comorbidities. This study seeks to evaluate the adherence of primary care
      physicians to age- and condition-specific preventive care in a cohort of adults
      with Down syndrome. METHODS: In this retrospective observational cohort study,
      preventive screening was evaluated in patients with Down syndrome aged 18-45
      years who received primary care in an academic medical centre from 2000 to 2008.
      Comparisons were made based on the field of patients' primary care providers
      (Family or Internal Medicine). RESULTS: This cohort included 62 patients, median
      index age = 33 years. Forty per cent of patients received primary care by Family
      Physicians, with 60% seen by Internal Medicine practices. Patient demographics,
      comorbidities and overall screening patterns were similar between provider
      groups. Despite near universal screening for obesity and hypothyroidism,
      adherence to preventive care recommendations was otherwise inconsistent.
      Screening was 'moderate' (50-80%) for cardiac anomalies, reproductive health,
      dentition, and the combined measure of behaviour, psychological, or memory
      abnormalities. Less than 50% of patients were evaluated for obstructive sleep
      apnea, atlanto-axial instability, hearing loss or vision loss. CONCLUSIONS: We
      observed inconsistent preventive care in adults with Down syndrome over this 8.5
      year study. This is concerning, given that the adverse effects of many of these
      conditions can be ameliorated if discovered in a timely fashion. Further studies
      must evaluate the implications of screening practices and more timely
      identification of comorbidities on clinical outcomes.

PMID- 22463765
TI  - Nutritional quality of children's school lunches: differences according to food
      source.
AB  - OBJECTIVE: To assess the nutritional quality of lunchtime food consumption among
      elementary-school children on Prince Edward Island according to the source of
      food consumed (home v. school). DESIGN: Students completed a lunchtime food
      record during an in-class survey. Dietary adequacy was assessed by comparing
      median micronutrient intakes with one-third of the Estimated Average Requirement;
      median macronutrient intakes were compared with the Acceptable Macronutrient
      Distribution Ranges. The Wilcoxon signed rank test was used to assess differences
      in nutrient intakes according to source of food consumed. SETTING: Elementary
      schools in Prince Edward Island, Canada. SUBJECTS: Grade 5 and 6 students (n
      1980). RESULTS: Foods purchased at school were higher in nutrient density for ten
      micronutrients (Ca, Mg, K, Zn, vitamin A, vitamin D, riboflavin, niacin, vitamin
      B6 and vitamin B12) compared with packed lunch foods from home, which were higher
      in three micronutrients (Fe, vitamin C and folate). School lunches provided
      sufficient protein but were higher in sugar and fat than home lunches. Foods
      brought from home were higher in carbohydrates, fibre and Na than foods purchased
      at school. CONCLUSIONS: The overall nutritional quality of lunches was poor,
      regardless of source. A significant proportion of foods consumed by the students
      came from home sources; these were lower nutritional quality and were higher in
      Na than foods offered at school. Findings suggest that improving the dietary
      habits of school-aged children will require a collaborative effort from multiple
      stakeholders, including parents.

PMID- 22463764
TI  - The essential role of protein kinase Cdelta in diabetes-induced neural tube
      defects.
AB  - BACKGROUND: Maternal diabetes causes neural tube defects (NTDs) in the embryos
      via activating protein kinase Cs (PKCs), which regulate programmed cell death
      (apoptosis). The aims of this study are to investigate the role of proapoptotic
      PKCdelta in NTD formation and the underlying mechanisms. METHODS: PKCdelta
      heterozygous (pkcdelta(+/-)) female mice were diabetic (DM) induced by
      intravenous injection of streptozotocin. Occurrence of NTDs was evaluated at
      embryonic day 11.5 and compared between wild type (WT) and PKCdelta homozygous
      (pkcdelta(-/-)) embryos. Changes in oxidative and endoplasmic reticulum (ER)
      stress-associated factors and stress-response c-Jun N-terminal kinases (JNKs)
      were assessed using Western blot assay. RESULTS: Compared to DM/WT, the
      DM/PKCdelta(-/-) embryos had significantly lower NTD rate and lower levels of
      oxidative and ER stress factors and JNK activation. These values were similar to
      those in the non-diabetic control group. CONCLUSION: PKCdelta plays a critical
      role in diabetes-induced NTDs, potentially through increasing oxidative and ER
      stress and JNK-associated stress-response pathways.

PMID- 22463767
TI  - Stem cells and tissue regeneration.

PMID- 22463766
TI  - Human telomerase RNA component (hTERC) gene amplification detected by FISH in
      precancerous lesions and carcinoma of the larynx.
AB  - BACKGROUND: Gain of 3q26 is frequently observed in squamous cell carcinomas of
      mucosal origin, including those originating in the head and neck region. The
      human telomerase RNA component (hTERC) gene, which is located on chromosome 3q26,
      encodes for an RNA subunit of telomerase that maintains the length of telomeres
      through cellular divisions, and is activated in malignant diseases. The present
      study was designed to detect hTERC amplification in laryngeal lesions and
      evaluate whether this might serve as a supportive biomarker in histopathological
      analysis for in the diagnosis of laryngeal lesions. METHODS: Fluorescent in situ
      hybridization (FISH) was applied on formalin-fixed paraffin-embedded blocks of 93
      laryngeal specimens, including 14 normal epithelium (NE), 15 mild dysplasia (Md),
      18 moderate dysplasia (MD), 16 severe dysplasia (SD), 9 carcinoma in situ (CIS),
      and 21 invasive carcinoma (IC)). RESULTS: By histopathologic examination, hTERC
      amplification rates in NE, Md, MD, SD, CIS and IC cases were 0% (0/14), 13.33%
      (2/15), 72.22% (13/18), 81.25% (13/16), 100% (9/9) and 100% (21/21),
      respectively. Amplification of hTERC was significantly associated with
      histopathologic diagnosis (P < 0.0001). The percentage of hTERC amplification in
      patients with MD, SD, CIS, and IC was significantly higher than those with NE or
      Md (P < 0.0001). The number of cells with abnormal signals increased and the
      abnormal signal patterns were diversified with increasing severity of laryngeal
      dysplasia (P < 0.0001). CONCLUSIONS: The hTERC amplification is important in the
      development of laryngeal squamous cell carcinoma (LSCC). FISH detection of hTERC
      amplification may provide an effective approach in conjunction with
      histopathologic evaluation for differential diagnosis of laryngeal lesions.
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/2226606266791985.

PMID- 22463768
TI  - Artificial construction of the layered Ruddlesden-Popper manganite La2Sr2Mn3O10
      by reflection high energy electron diffraction monitored pulsed laser deposition.
AB  - Pulsed laser deposition has been used to artificially construct the n = 3
      Ruddlesden-Popper structure La(2)Sr(2)Mn(3)O(10) in epitaxial thin film form by
      sequentially layering La(1-x)Sr(x)MnO(3) and SrO unit cells aided by in situ
      reflection high energy electron diffraction monitoring. The interval deposition
      technique was used to promote two-dimensional SrO growth. X-ray diffraction and
      cross-sectional transmission electron microscopy indicated that the trilayer
      structure had been formed. A site ordering was found to differ from that expected
      thermodynamically, with the smaller Sr(2+) predominantly on the R site due to
      kinetic trapping of the deposited cation sequence. A dependence of the out-of
      plane lattice parameter on growth pressure was interpreted as changing the oxygen
      content of the films. Magnetic and transport measurements on fully oxygenated
      films indicated a frustrated magnetic ground state characterized as a spin glass
      like magnetic phase with the glass temperature T(g) ~ 34 K. The magnetic
      frustration has a clear in-plane (ab) magnetic anisotropy, which is maintained up
      to temperatures of 150 K. Density functional theory calculations suggest
      competing antiferromagnetic and ferromagnetic long-range orders, which are
      proposed as the origin of the low-temperature glassy state.

PMID- 22463769
TI  - [Guide to buying a camera for dermatological photography].
AB  - Choosing a camera for use in the dermatology office is difficult, particularly in
      the case of a digital camera because the market is constantly evolving. This
      article explains the features that should be taken into account, including camera
      type, sensor, lens and macro capability, aperture priority mode, screen,
      viewfinder, operating speed, flash, battery, memory card, and image format. The
      most recent advances in the field of digital photography relevant to the
      dermatologist are discussed.

PMID- 22463770
TI  - [Vascular patterns in dermoscopy].
AB  - Under the right conditions, dermoscopy allows us to observe the vascular features
      of many different types of skin lesions. The visualization and identification of
      vessels with a characteristic morphology can be the key to diagnosis, especially
      in hypopigmented lesions in which the typical pigmented structures are not
      visible. Some of the more characteristic associations are the presence of crown
      vessels in sebaceous hyperplasia, arborizing telangiectasias in basal cell
      carcinoma, comma-shaped vessels in intradermal and compound nevi, dotted vessels
      in Spitz nevi and melanoma, and hairpin vessels in seborrheic keratoses. The
      recognition of distinctive vascular features can be of great help in the
      diagnosis of many types of skin lesions, and very often such patterns are the
      only key to the diagnosis of melanoma.

PMID- 22463771
TI  - Factor structure and psychometric properties of the trier inventory for chronic
      stress (TICS) in a representative German sample.
AB  - BACKGROUND: Chronic stress results from an imbalance of personal traits,
      resources and the demands placed upon an individual by social and occupational
      situations. This chronic stress can be measured using the Trier Inventory for
      Chronic Stress (TICS). Aims of the present study are to test the factorial
      structure of the TICS, report its psychometric properties, and evaluate the
      influence of gender and age on chronic stress. METHODS: The TICS was answered by
      N = 2,339 healthy participants aged 14 to 99. The sample was selected by random
      route sampling. Exploratory factor analyses with Oblimin-rotated Principal Axis
      extraction were calculated. Confirmatory factor analyses applying Robust Maximum
      Likelihood estimations (MLM) tested model fit and configural invariance as well
      as the measurement invariance for gender and age. Reliability estimations and
      effect sizes are reported. RESULTS: In the exploratory factor analyses, both a
      two-factor and a nine-factor model emerged. Confirmatory factor analyses resulted
      in acceptable model fit (RMSEA), with model comparison fit statistics
      corroborating the superiority of the nine-factor model. Most factors were
      moderately to highly intercorrelated. Reliabilities were good to very good.
      Measurement invariance tests gave evidence for differential effects of gender and
      age on the factor structure. Furthermore, women and younger individuals,
      especially those aged 35 to 44, tended to report more chronic stress than men and
      older individuals. CONCLUSIONS: The proposed nine-factor structure could be
      factorially validated, results in good scale reliability, and heuristically can
      be grouped by two higher-order factors: "High Demands" and "Lack of
      Satisfaction". Age and gender represent differentiable and meaningful
      contributors to the perception of chronic stress.

PMID- 22463772
TI  - Superovulation and multiple birth: in search of kryptonite.
AB  - The contribution of superovulation and ovulation induction to the multiple
      pregnancy epidemic in the U.S. is substantial. Further understanding of the
      contributing factors and, most importantly, preventive strategies are needed.

PMID- 22463773
TI  - History and challenges surrounding ovarian stimulation in the treatment of
      infertility.
AB  - OBJECTIVE: To examine the history of superovulation for ovulation induction, its
      contributions to reproductive medicine, and its impact on multiple births.
      DESIGN: A search of the relevant literature using PubMed and other online tools.
      RESULT(S): Infertility has been a condition known and studied for thousands of
      years. However, it was not until this past century that effective treatments were
      developed. With the advancement of our knowledge of the hypothalamic-pituitary
      axis, therapies utilizing gonadotropins were developed to stimulate ovulation.
      Not only could we now treat anovulatory infertility but also induce
      superovulation for IVF. With these successes came consequences, including
      increased multiple pregnancies. Several countries recognized the high costs
      associated with multiple births and implemented regulations on the infertility
      industry. The rate of triplet and higher-order multiples has declined over the
      past decade. This is largely attributed to a decreased number of embryos
      transferred. Nonetheless, the twin rate has remained consistently high.
      CONCLUSION(S): Superovulation has become a routine medical therapy used for
      ovulation induction and IVF. With the development of this technology have come
      effective therapies for infertility and new ethical and medical challenges. Since
      the advent of gonadotropin therapy we have already developed technologies to
      improve monitoring and decrease hyperstimulation and high-order multiple
      pregnancies. In the future we anticipate new tools devised to optimize one embryo
      for one singleton live birth.

PMID- 22463774
TI  - Ovarian stimulation and intrauterine insemination at the quarter centennial:
      implications for the multiple births epidemic.
AB  - Ovarian stimulation and intrauterine insemination (OS/IUI), a mainstay of current
      infertility therapy and a common antecedent to IVF, is a significant driver of
      the multiple births epidemic. Redress of this challenge, now marking its quarter
      centennial, will require a rethinking of current practice patterns. Herein we
      explore prospects for prevention, mitigation, and eventual resolution. We
      conclude that the multiple births attributable to OS/IUI may not be entirely
      preventable but that the outlook for their mitigation is promising, if in need of
      solidification. Specifically, we observe that low-dose (<= 75 IU) gondotropin,
      clomiphene, and especially off-label letrozole regimens outperform high-dose (>=
      150 IU) gonadotropin counterparts in the gestational plurality category while
      maintaining comparable per-cycle pregnancy rates. Accordingly we recommend that,
      subject to appropriate exceptions, high-dose gonadotropin regimens be used
      sparingly and that whenever possible they be replaced with emerging alternatives.
      Finally, we posit that OS/IUI is not likely to be superseded by IVF absent
      further commoditization and thus greater affordability.

PMID- 22463775
TI  - Gonadotropin therapy: a 20th century relic.
AB  - Gonadotropin therapy has been a cornerstone of infertility therapy for half a
      century. From the very beginning, its use has been associated with a high rate of
      multiple births, particularly high order multiples, and ovarian hyperstimulation
      syndrome. Initially, success rates seemed acceptable when used for superovulation
      (SO)/IUI therapy. However, as data from RCTs have emerged, reported outcomes
      suggest that we question the use of injectible gonadotropins. This manuscript
      examines the studies that have challenged gonadotropin use for SO/IUI and other
      research that supports reduced doses of gonadotropins for IVF. We examine the
      challenges for its continued use for SO/IUI and for moving to lower doses
      worldwide for IVF. We propose a future that views gonadotropins as a relic of the
      twentieth century.

PMID- 22463776
TI  - Short communication: initiation of an abacavir-containing regimen in HIV-infected
      adults is associated with a smaller decrease in inflammation and endothelial
      activation markers compared to non-abacavir-containing regimens.
AB  - Abacavir has been associated with myocardial infarction in several studies. This
      may be related to inflammation and endothelial cell activation. We compared
      changes in inflammation and endothelial activation markers between antiretroviral
      naive adults initiating zidovudine, lamivudine, abacavir, and nonnucleoside
      reverse transcriptase inhibitor (NNRTI) or this regimen without abacavir. Changes
      in soluble tumor necrosis factor receptors-I, -II (sTNFR-I, -II), high
      sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1
      (sVCAM-1) from baseline (pre-ART) to a second time point about 24 weeks after
      initiating antiretroviral therapy (ART) were compared between groups using
      multivariable linear regression. A total of 37 met eligibility criteria; 12
      received abacavir. The median (interquartile range) age was 37 years (27-45).
      Most were men (32/37), African-American (15/37), or white (15/37). The median
      nadir CD4(+) and baseline HIV-1 RNA were 230 cells/mm(3) (180-301) and 82,642
      copies/ml (34,400-204,703). In all, 15/30 smoked, 7/37 had hypertension, 1/37 had
      diabetes, and 1/37 had hyperlipidemia. None had coronary or renal disease.
      Changes in CD4(+) and HIV-1 RNA level and timing of stored samples with regard to
      ART initiation were not different between groups. In univariable analysis, log
      transformed percent change in sTNFR-I (p=0.05) and -II (p=0.04) showed
      significant between-group differences and trended toward significance for sVCAM-1
      (p=0.08). These markers decreased less in the abacavir group. After adjustment
      for confounders, significantly less decrease for sTNFR-II and sVCAM-1 was seen
      for those receiving the abacavir-containing regimen. When taken with an NNRTI,
      abacavir induced a smaller decrease in inflammation biomarkers in this cohort,
      suggesting a possible proinflammatory effect of this nucleoside analogue.

PMID- 22463777
TI  - Culex genome is not just another genome for comparative genomics.
AB  - Formal publication of the Culex genome sequence has closed the human disease
      vector triangle by meeting the Anopheles gambiae and Aedes aegypti genome
      sequences. Compared to these other mosquitoes, Culex quinquefasciatus possesses
      many specific hallmark characteristics, and may thus provide different angles for
      research which ultimately leads to a practical solution for controlling the ever
      increasing burden of insect-vector-borne diseases around the globe. We argue the
      special importance of the cosmopolitan species- Culex genome sequence by invoking
      many interesting questions and the possible of potential of the Culex genome to
      answer those.

PMID- 22463778
TI  - Allelematch: an R package for identifying unique multilocus genotypes where
      genotyping error and missing data may be present.
AB  - We present allelematch, an R package, to automate the identification of unique
      multilocus genotypes in data sets where the number of individuals is unknown, and
      where genotyping error and missing data may be present. Such conditions commonly
      occur in noninvasive sampling protocols. Output from the software enables a
      comparison of unique genotypes and their matches, and facilitates the review of
      differences between profiles. The software has a variety of applications in
      molecular ecology, and may be valuable where a large number of samples must be
      processed, unique genotypes identified, and repeated observations made over space
      and time. We used simulations to assess the performance of allelematch and found
      that it can reliably and accurately determine the correct number of unique
      genotypes (+/- 3%) across a broad range of data set properties. We found that the
      software performs with highest accuracy when genotyping error is below 4%. The R
      package is available from the Comprehensive R Archive Network (http://cran.r
      project.org/). Supplementary documentation and tutorials are provided.

PMID- 22463779
TI  - [Invasive mycoses in the critically ill patient].

PMID- 22463780
TI  - [Towards an early diagnosis of invasive candidiasis in the critically ill
      patient].
AB  - The management of invasive fungal infections in critically ill patients, from
      diagnosis to selection of the therapeutic protocol, is often a challenge. Early
      diagnosis and treatment are associated with a better prognosis, but apart from
      cases with positive cultures from blood or fluid/tissue biopsy, diagnosis is
      neither sensitive nor specific, and there is a need for specific markers in these
      diseases. Serodiagnostic assays such as mannan antigen, mannan antibodies,
      Candida albicans germ-tube antibodies or (1->3)-beta-D-glucan detection, and
      molecular techniques for the detection of fungal-specific DNA have been developed
      with promising results in critical care settings. One of the main features in
      diagnosis is the evaluation of risk factors for infection, which will identify
      patients in need of preemptive or empirical treatment. Clinical scores were built
      from those risk factors. The combination of prediction rules and non-culture
      microbiological tools could be currently be the key to improving the diagnosis
      and prognosis of invasive fungal infections in critically ill patients.

PMID- 22463781
TI  - [Persistent candidemia in a renal-pancreatic transplant patient].
AB  - BACKGROUND: In recent decades, there has been an increase in the survival of
      recipients of solid organ transplants related to the improvement of the surgical
      technique, the introduction of protocols for immunosuppressive therapy, and the
      use of antimicrobial prophylaxis. Nonetheless, invasive fungal infection (IFI) is
      currently the major cause of morbidity and mortality in this group of patients.
      Invasive candidiasis is the most common IFI found after renal transplantation and
      is usually associated with total parenteral nutrition, broad-spectrum antibiotic
      therapy and abdominal surgery. CLINICAL CASE: We report the case of a recent
      kidney-pancreas transplant recipient who developed a persistent catheter-related
      candidemia caused by Candida glabrata. The patient was treated with anidulafungin
      and had a good clinical course with no significant drug interactions. We discuss
      the possible causes and diagnostic and therapeutic alternatives of this kind of
      infection.

PMID- 22463782
TI  - [Candida peritonitis in a haemodynamically stable patient. First choice of
      antifungal treatment ... fluconazole?].
AB  - BACKGROUND: Candida peritonitis in postoperative patients is an independent
      predictor of mortality. Empirical early antifungal therapy should be started in
      these patients, since according to the results of studies in patients with
      candidemia, this has an impact on the prognosis. The treatment recommended by
      clinical practice guidelines in patients with haemodynamic instability are
      candins, but they do not make explicit recommendations for patients with
      dysfunction of other organs, or high lactate levels. CASE REPORT: A case of
      rescue treatment with anidulafungin in a patient with candidemia and Candida
      glabrata peritonitis postoperative haemodynamically stable, but with an acute
      renal failure and elevated plasma lactate, is reported. We discuss the antifungal
      treatment recommendations established by clinical practice guidelines.
      CONCLUSIONS: One conclusion based on this case is that the haemodynamic
      instability as a marker of severe sepsis must be equated with dysfunction of any
      organ and/or a plasma lactate level >= 2.5 mmol/l in order to advocate candins as
      an antifungal treatment. In addition, it should be emphasised that anidulafungin
      was effective in a clinically difficult patient with candidemia and Candida
      peritonitis, even when used as late rescue antifungal treatment.

PMID- 22463783
TI  - [Echinocandins in a critically ill patient during continuous venovenous renal
      replacement].
AB  - BACKGROUND: Critically ill patients with invasive candidiasis (IC) often suffer
      renal failure, which sometimes requires continuous renal replacement techniques
      (CRRT). Echinocandins are the first line treatment for IC in critically ill
      patients with mild or severe illness. Their elimination during CRRT should be
      negligible due to their pharmacokinetic and pharmacodynamic (PK/PD) profile, and
      dose adjustment are not needed, as suggested by the few reported clinical
      studies. CLINICAL CASE: This is the case of a 66 year old male who underwent
      surgery due to peritonitis secondary to intestinal suture dehiscence. The patient
      was admitted to ICU with septic shock symptoms and multiple organ dysfunction
      syndrome (MODS), and CRRT was started. Anidulafungin was prescribed at the usual
      dosage due to the IC risk factors present, and the observation of yeasts in the
      peritoneal fluid. Anidulafungin was selected due to the hepatic failure suffered
      by the patient. An isolate of Candida albicans susceptible to fluconazole was
      cultured from peritoneal fluid and rectal exudates. However, anidulafungin was
      maintained due to the MODS and observing the clearance of fluconazole during
      CRRT. The patient's condition improved favourably, being moved to the surgical
      ward 20 days after the surgery. CONCLUSIONS: Echinocandins, due to their PK/PD
      profile, could be safely given at usual doses to critically ill patients
      undergoing CRRT. However, new studies are required to strengthen this
      recommendation. Its extrahepatic metabolism makes anidulafungin a more attractive
      option among echinocandins and other antifungals when used in patients with
      different degrees of hepatic failure.

PMID- 22463785
TI  - [Invasive candidiasis in severely ill burned patients].
AB  - BACKGROUND: The advances in burn care therapy have extended considerably the
      survival of seriously burned patients, exposing them to infectious complications,
      notably fungal infections. Due to the difficulty in the diagnosis of invasive
      mycoses and their high associated mortality rates, approaches to prophylactic or
      pre-emptive antifungal therapy in high-risk burned patients have been proposed,
      although these guidelines remain controversial. On the other hand, the management
      of these conditions is a serious problem, especially in critically ill patients
      with multiorgan failure, including severely ill burn patients due to the shortage
      of available antifungal agents. However, in the last several years, the range of
      antifungal agents has been significantly extended, which have led to an
      improvement in the treatment of invasive fungal infection in this population.
      CLINICAL CASE: We report a case of invasive candidiasis in a severelly ill burns
      patient successfully treated with an echinocandin. In this case report, current
      treatment options are discussed, and a review of the literature of previously
      published cases is made. CONCLUSIONS: There are still significant gaps in our
      knowledge of the optimal diagnostic and management approach for invasive
      candidiasis in burn patients. Prospective studies are needed in this population
      to optimise management and improve outcomes in this state of high morbidity and
      mortality.

PMID- 22463784
TI  - [Pulmonary aspergillosis in a non-immunocompromised critically ill patient].
AB  - BACKGROUND: In non-immunocompromised patients admitted to intensive care
      departments or units (ICU), it is difficult to establish a definitive diagnosis
      of pulmonary aspergillosis because the signs and symptoms of this infectious
      disease are non-specific, and serological techniques are not very specific as
      well. For this reason, a diagnosis of possible pulmonary aspergillosis is
      initially established, and the starting of the treatment is controversial. CASE
      REPORT: An immunocompetent subject had a work-related accident after a fall,
      which resulted in multiple injuries (head, thorax, lower extremities). The
      patient required mechanical ventilation since admission. On the second week of
      ICU admission, he showed a clinical presentation of respiratory infection with
      fever, purulent secretions, bilateral pulmonary infiltrates and repeated
      isolation of Mucor and Aspergillus fumigatus in bronchial secretions and
      pharyngeal swabs. The patient was treated with amphotericin B lipid complex and
      voriconazole with an excellent clinical and radiological outcome. CONCLUSIONS:
      Combined treatment of antifungal agents, in this case amphotericin B lipid
      complex and voriconazole, is a therapeutic possibility to be considered in
      patients who failed to respond to initial antifungal monotherapy.

PMID- 22463786
TI  - [Invasive candidiasis in a lung retransplantation recipient].
AB  - BACKGROUND: Lung-graft loss is a potential problem for the majority of lung
      transplant recipients. Retransplantation could be a treatment option, despite
      significant morbidity and mortality due to infectious complications. The
      epidemiology, clinical presentation and early treatment are still the basis of
      the overall approach to the fungal invasive infection after repeated transplant.
      CLINICAL CASE: This is the case of a 29 year-old woman who underwent a left lung
      retransplantation due to bronchiolitis obliterans syndrome and developed Candida
      albicans invasive disease. She received the usual prophylaxis with nebulized
      liposomal amphotericin B and was also treated with anidulafungin. She received
      corticosteroid therapy and plasma exchange as acute lung transplant rejection was
      suspected with subsequent progressive deterioration and death. In the culture of
      blood samples yeasts were isolated, later identified as C. albicans resistant to
      fluconazole, caspofungin and micafungin (MCI 128 MUg/ml, 8 MUg/ml, 4 MUg/ml,
      respectively) and susceptible to anidulafungin and amphotericin B (MCI 0.25
      MUg/ml, 0.5 MUg/ml, respectively). CONCLUSIONS: The empirical management of acute
      transplant rejection with corticosteroid boluses and plasma exchange can help to
      spread the underlying and undiagnosed fungal infection. It is considered that an
      increase in the regular dose of anidulafungin is necessary after plasma exchange.
      To date, fungal echinocandin resistance did not seem to be a major cause for
      concern in the treatment of patients with invasive mycoses. However, there is
      increasing evidence of natural and acquired resistance resulting in life
      threatening infections and clinical failure.

PMID- 22463787
TI  - [Clinical features of critically ill patients with invasive fungal infection].
AB  - BACKGROUND: Invasive fungal infection (IFI) is an entity that encompasses
      different types of infections caused by different types of those fungi pathogenic
      for humans. In the setting of critically ill patients with multiple and often
      concurrent risk factors and comorbidities the most common are those caused by the
      Candida and Aspergillus species. Among the characteristics of IFI in critically
      ill patients, three aspects can be highlighted: those related to the host (e.g.:
      risk factors, clinical severity), those related with the pathogen (sensitivity,
      virulence), or those concerning antifungal treatment (spectrum, features PK / PD,
      safety, interactions). The fungus that most often causes an IFI in critically ill
      patients is Candida; the most common type infections are candidemia, Candida
      peritonitis and catheter-related infections. In recent years new antifungal
      treatments have expanded the therapeutic options, with echinocandins as a clear
      choice, often the first in the latest guidelines in critically ill patients with
      IFI. CASE REPORT: We report the case of a critically ill patient having the most
      common risk factors, multiple organ dysfunction and development of an IFI. The
      complexity of establishing an antifungal treatment from the moment of its
      inception, its setting, and the considerations of the different therapeutic
      possibilities according to organ dysfunction of the patient are discussed. The
      antifungal treatment options mentioned in the current guidelines and
      recommendations are also evaluated. CONCLUSIONS: The most common fungal infection
      in critically ill patients is invasive candidiasis, with candidemia or candida
      peritonitis being the most frequent clinical presentations. Candins have brought
      new possibilities for treating these complex patients due to their good safety
      profile and clinical efficacy.

PMID- 22463788
TI  - [Antifungal treatment options in the critically ill patient].
AB  - Invasive fungal infections, especially in the critical care setting, have become
      an excellent target for prophylactic, empiric, and pre-emptive therapy
      interventions due to their associated high morbidity, mortality rate, increased
      incidence, and healthcare costs. For these reasons, new studies and laboratory
      tests have been developed over the last few years in order to formulate an early
      therapeutic intervention strategy in an attempt to reduce the high mortality rate
      associated with these infections. In recent years, evidence-based studies have
      shown the roles that the new antifungal drugs play in the treatment of invasive
      mycosis in seriously ill and complex patients, although data from critically ill
      patients are more limited. New antifungal agents have been analyzed in different
      clinical situations in critical care units, and the increasing number of non
      Candida albicans species suggest that the application of early echinocandin
      therapy in critically ill patients with invasive candidiasis is a good option.
      Voriconazole should be recommended for invasive aspergillosis as a first line
      option.

PMID- 22463789
TI  - First report of venereal and vertical transmission of canine leishmaniosis from
      naturally infected dogs in Germany.
AB  - BACKGROUND: Canine leishmaniosis (CanL) is a zoonotic disease caused by
      Leishmania (L.) infantum. It is endemic to several tropical and subtropical
      countries but also to the Mediterranean region. It is transmitted by phlebotomine
      sandflies but occasional non-vector transmissions have been reported, including
      vertical and horizontal transmission. FINDINGS: The authors report a case of CanL
      in a female boxer dog from Dusseldorf, Germany, that had never been in an endemic
      region. A serum sample from the bitch was tested positive for antibodies against
      Leishmania (IFAT 1:2,000, ELISA 72). The bitch had whelped three litters, and one
      puppy from the third litter was also found to be seropositive for Leishmania
      antibodies (IFAT 1:4,000, ELISA 78). CONCLUSIONS: Up to now, despite intensive
      searching, the occurrence of sandflies could not be proved in the bitch's region
      of origin. Thus, vertical and horizontal transmission are to be discussed as
      possible ways of infection. This may be the first report of venereal and vertical
      transmission of L. infantum in naturally infected dogs in Germany.

PMID- 22463790
TI  - Involvement of Notch signaling pathway in regulating IL-12 expression via c-Rel
      in activated macrophages.
AB  - Macrophages play an important role both in innate and adaptive immune responses.
      Treatment with interferon (IFN) gamma together with lipopolysaccharide (LPS)
      activates pro-inflammatory macrophages which secrete various pro-inflammatory
      cytokines including IL-12. IL-12 promotes a Th1 type immune response by directly
      controlling the differentiation of CD4(+) T helper 1 cells. Activation of Notch
      signaling pathway was reported in activated macrophages but the involvement of
      this signaling pathway in IL-12 expression has not been documented. In this
      study, we investigated the role of Notch signaling in regulating expression of
      the IL-12/IL-23 subunit, IL-12p40. Using a gamma-secretase inhibitor (GSI) to
      inhibit Notch signaling, we observed a profound decrease in il12p40 mRNA levels
      and IL-12p70 secretion upon IFNgamma/LPS stimulation. On the other hand,
      overexpression of activated form of Notch1 in activated RAW264.7 macrophage-like
      cell lines significantly increased the level of il12p40 mRNA. GSI treatment did
      not affect the expression of irf5, a master regulator of il12p40 transcription in
      macrophages. Detailed analysis of the signaling cascades that were affected by
      this inhibition showed that c-Rel nuclear translocation was inhibited and Erk1/2
      activation was compromised by GSI treatment. Addition of exogenous tumor necrosis
      factor (TNF) alpha only partially rescued the expression of il12p40 in the
      presence of GSI. Unexpectedly, inhibition of Notch signaling using a dominant
      negative (DN) Mastermind-like (MAML) transcription co-activator, did not affect c
      Rel nuclear localization upon activation or il12p40 mRNA levels, suggesting that
      the transcriptional activity of Notch signaling is dispensable for the activation
      of c-Rel. These results strongly suggest that Notch signaling in activated
      macrophages is involved in regulating the expression of il12p40 directly via c
      Rel and indirectly via TNFalpha production.

PMID- 22463791
TI  - A wound-like inflammatory aortic response in chronic portal hypertensive rats.
AB  - Long-term prehepatic portal hypertension in the rat produces a low-grade
      splanchnic inflammation with liver steatosis and dyslipidemia. It has been
      suggested that in this experimental model these inflammatory alterations could
      represent a risk factor of vascular disease. Therefore, our aim was to
      investigate whether long-term prehepatic portal hypertension (PH) induces
      vascular pathology, fundamentally inflammatory aortopathy. Male Wistar sham
      operated (SO) rats and rats with triple partial portal vein ligation in the very
      long-term (22 months) of postoperative evolution were used. Serum lipid profile,
      pro- and anti- inflammatory cytokines and ACTH and corticosterone were assayed by
      spectrophotometric and ELISA techniques. Aorta mRNA expression of oxidative and
      nitrosative stress enzymes, NFkappaB e IkappaB, immune-related cytokine
      production and vascular fibrosis parameters, were evaluated by real time RT-PCR.
      In addition, aortic p22phox subunit immunostaining, morphometry and vascular
      fibrosis in aorta were analyzed. PH rats have increased serum cholesterol,
      triglyceride, low-density lipoproteins (LDL) and very low-density lipoproteins
      (VLDL), while high-density lipoproteins (HDL) were lower than in SO rats. Serum
      ACTH and corticosterone decreased in PH rats. Also, serum TNF-alpha, IL-1beta and
      IL-6 were significantly higher in PH-rats. Portal hypertensive-rats showed aortic
      oxidative stress with increased mRNA expressions of NAD(P)H oxidase p22phox, XDh,
      SOD and eNOS; higher aortic levels of pro-inflammatory cytokines, including TNF
      alpha, IL-1beta and IL-6; remodeling markers, like collagen I, CTGF and MMP-9;
      and finally, higher protein production of p22phox and collagen and extracellular
      matrix density were significantly higher in rats with PH. The results from the
      current study suggest that very long-term prehepatic portal hypertension in rats
      induces an abdominal aortic inflammatory and fibrotic response. Therefore, it
      could be considered that portal hypertension aggravates aortic inflammaging and
      one of its more severe complications, which is remodeling by a wound healing
      reaction.

PMID- 22463792
TI  - Polymerase chain reaction testing for Clostridium difficile.

PMID- 22463793
TI  - Manganese is required for oxidative metabolism in unstressed Bradyrhizobium
      japonicum cells.
AB  - Recent studies of Mn(2+) transport mutants indicate that manganese is essential
      for unstressed growth in some bacterial species, but is required primarily for
      induced stress responses in others. A Bradyrhizobium japonicum mutant defective
      in the high-affinity Mn(2+) transporter gene mntH has a severe growth phenotype
      under manganese limitation, suggesting a requirement for the metal under
      unstressed growth. Here, we found that activities of superoxide dismutase and the
      glycolytic enzyme pyruvate kinase were deficient in an mntH strain grown under
      manganese limitation. We identified pykM as the only pyruvate kinase-encoding
      gene based on deficiency in activity of a pykM mutant, rescue of the growth
      phenotype with pyruvate, and pyruvate kinase activity of purified recombinant
      PykM. PykM is unusual in that it required Mn(2+) rather than Mg(2+) for high
      activity, and that neither fructose-1,6-bisphosphate nor AMP was a positive
      allosteric effector. The mntH-dependent superoxide dismutase is encoded by sodM,
      the only expressed superoxide dismutase-encoding gene under unstressed growth
      conditions. An mntH mutant grew more slowly on pyruvate under manganese-limited
      conditions than did a pykM sodM double mutant, implying additional manganese
      dependent processes. The findings implicate roles for manganese in key steps in
      unstressed oxidative metabolism in B. japonicum.

PMID- 22463794
TI  - Biomarkers, subgroup evaluation, and clinical trial design.
AB  - Advances in clinical and basic sciences are raising the potential to use genetic
      and clinical biomarkers to identify a subgroup of patients who would most likely
      benefit from treatment, and to evaluate the benefit of treatment in that
      subgroup. To make full use of this potential, special clinical trial designs and
      analyses are needed. For identifying and evaluating a subgroup based on a single
      continuous biomarker, the most informative approach is the biomarker-analysis
      design, which is a randomized trial whose analysis involves estimation of the
      treatment benefit within patient groups defined with respect to various cutpoints
      or intervals of the biomarker. For identifying and evaluating a subgroup
      considering a range of possible markers, the adaptive signature design is
      recommended. In the adaptive signature design, participants are randomly split
      into training and test samples, a rule for creating the subgroup is formulated in
      the training sample, and treatment benefit is estimated in the test sample. The
      adaptive signature design can be usefully extended via the sliding-window
      subgroup plot that was originally developed for the biomarker-analysis design.

PMID- 22463795
TI  - The impact of antibiotics on the gut microbiota as revealed by high throughput
      DNA sequencing.
AB  - Treatment with broad spectrum antibiotics can have a detrimental impact on the
      commensal bacteria present in the gut. The extensive nature of the collateral
      damage caused by such compounds has been revealed more starkly than ever before
      through the application of high throughput DNA sequencing-based technologies to
      investigate resulting microbial populations. Here we review the findings of such
      studies and discuss the strategies available to minimize such negative impacts.

PMID- 22463796
TI  - Osteoclasts: malefactors of disease and targets for treatment.
AB  - The osteoclast represents one of the most highly specialized cells within the
      human body, which operates within a microenvironment of diverse cellular
      populations and matrix proteins. Moreover, the osteoclast directly effects and is
      affected by these surroundings in a delicate relationship of cellular
      differentiation, bone resorption, and controlled apoptosis. The result is the
      maintenance of adequate bone mass throughout life. Unsurprisingly, disturbances
      within this environment or the molecular regulation of normal osteoclast biology
      has profound effects on skeletal homeostasis and crippling physical
      manifestations. This review will summarize current literature describing normal
      and pathological osteoclast biology and highlight the benefits of osteoclast
      targeted therapy to combat skeletal disorders.

PMID- 22463797
TI  - miRNAs at the crossroad between hematopoietic malignancies and autoimmune
      pathogenesis.
AB  - The study of microRNA (miRNA) regulation in the pathogenesis of autoimmune
      diseases and hematopoietic malignancies provides new understanding of the
      mechanisms of disease and is currently the focus of many researchers in the
      field. Autoimmune disorders and cancers of immune system comprise a wide range of
      genetically complex diseases that share certain aspects of dysregulated genetic
      networks, most notably deactivation of apoptosis. miRNA mechanisms control gene
      expression at the post-transcriptional level, linking mRNA processing and gene
      function. Considerable amount of data have been accumulated that indicate that
      the alteration of miRNA expression closely mirrors the development of immune
      system diseases and is likely to play a role in their pathogenesis. However, a
      knowledge gap remains in our understanding of how miRNA dysregulation and the
      specific effects of miRNAs on target gene expression underlay the disease
      phenotype. Here we review a number of studies describing miRNA alterations in
      autoimmune diseases and hematopoietic cancers and discuss potential miRNA
      regulated mechanisms that differentially influence the development of
      autoimmunity as compared to cancer progression.

PMID- 22463798
TI  - Aerobic exercise in the elderly: a key to successful aging.
AB  - A decline in maximal aerobic exercise capacity occurs across the adult age-span,
      accelerating in later years. This age-associated decline in aerobic capacity is
      accentuated by superimposed comorbidities common to the elderly such as cardiac,
      pulmonary, and peripheral artery disease. However, observational and training
      studies demonstrate significant improvement in peak oxygen consumption in both
      health and disease settings. In addition, exercise training exerts beneficial
      effects on blood pressure, lipids, glucose tolerance, bone density, depression,
      and quality of life. A major challenge to physicians and society is to increase
      the low participation rates of older adults in both home-based exercise and
      supervised exercise rehabilitation programs.

PMID- 22463799
TI  - TNF-alpha antagonism and cancer risk in rheumatoid arthritis: is continued
      vigilance warranted?
AB  - Rheumatoid arthritis (RA) is a chronic, systemic inflammatory arthritis that can
      lead to significant damage and dysfunction of involved joints. Prior to 1998,
      treatment options were limited to disease modifying anti-rheumatic drugs,
      commonly referred to as DMARDs like methotrexate, sulfasalazine,
      hydroxychloroquine, and gold salts. Tumor necrosis factor alpha (TNF-alpha) is a
      central cytokine that drives the inflammation in RA; hence inhibition of TNF
      alpha offers an attractive treatment strategy in RA. The introduction of TNF
      alpha inhibitors, a class of biologic DMARDs, has dramatically changed the
      treatment of RA as these are highly effective therapies. Medication-related
      adverse events remain a major problem in health care. This is true of the TNF
      alpha antagonists as well, with particular concerns about increased risks of
      infections and malignancy. Because clinical trials performed prior to medication
      approval are limited by the number and clinical complexity of participants and
      the duration of the trials, post-marketing surveillance is critical in
      identifying adverse events. In order to better clarify the safety issues related
      to the use of TNF-alpha inhibitors in RA, several studies using large
      observational registries along with pooled meta-analyses of these studies have
      been published. This review will summarize the data from these recent studies on
      the question of malignancy risk associated with TNF-alpha inhibitor use in RA. It
      is comforting that the data from these studies do not support an increased risk
      of cancer, except non-melanoma skin cancer, with the use of TNF-alpha antagonists
      in adults with RA.

PMID- 22463800
TI  - Novel immunotherapeutic approaches to improve rates and outcomes of
      transplantation in sensitized renal allograft recipients.
AB  - Although considerable progress has occurred in kidney transplantation, allograft
      loss remains a substantial unresolved issue, leading to increased morbidity,
      mortality, and costs. Preserving, protecting, and extending the functional
      integrity of allografts is paramount to providing maximal benefits. To this end,
      identifying critical immunopathologic pathways and biomarkers associated with
      allograft attrition, with attendant development of rational therapeutic
      interventions, has emerged as one of the most important objectives of transplant
      medicine. B-cells and donor-specific anti-HLA antibodies (DSA) are now recognized
      as important mediators of allograft injury and loss. These findings have led to a
      renewed interest in therapies that modify B-cells and antibodies. Early
      experience with desensitization protocols coupled with improved diagnostics for
      DSAs and renal pathology have greatly improved transplant rates and outcomes for
      patients once considered at high risk for poor outcomes. Therapies aimed at B
      cells and antibodies include high-dose intravenous immunoglobulin (IVIG), plasma
      exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing
      therapies include proteasome inhibitors aimed at plasma cells, newer monoclonal
      antibodies that block B-cell growth factors, and modifiers of complement-mediated
      injury. Here we discuss the importance of B-cells and DSAs as mediators of
      allograft injury and the evolution of therapies aimed at reducing their impact on
      allograft survival.

PMID- 22463801
TI  - The factors affecting end-of-life decision-making by physicians of patients with
      intellectual disabilities in the Netherlands: a qualitative study.
AB  - BACKGROUND: The aim of this study was to investigate the process of end-of-life
      decision-making regarding people with intellectual disabilities (ID) in the
      Netherlands, from the perspective of physicians. METHODS: This qualitative study
      involved nine semi-structured interviews with ID physicians in the Netherlands
      after the deaths of patients with ID that involved end-of-life decisions. The
      interviews were transcribed verbatim and analysed using Grounded Theory
      procedures. RESULTS: Four main contributory factors to the physicians decision
      making process were identified, three of which are related to the importance of
      relatives' wishes and opinions: (1) Involving relatives in decision-making. As
      they had assessed their patients as lacking capacity, the physicians gave very
      great weight to the opinions and wishes of the relatives and tended to follow
      these wishes. (2) Delegating quality of life assessments to relatives. Physicians
      justified their end-of-life decisions based on their medical assessment, but left
      the assessment of the patients' quality of life to relatives, despite having
      their own implicit opinion about quality of life. (3) Good working relationships.
      Physicians sought consensus with relatives and paid care staff, often giving
      greater weight to the importance of good working relationships than to their own
      assessment of the patient's best interest. (4) Knowledge of the patient's
      vulnerabilities. Physicians used their intimate, long-standing knowledge of the
      patient's fragile health. CONCLUSIONS: In order to take a more balanced decision,
      physicians should seek possibilities to involve patients with ID themselves and
      other stakeholders which are important for the patients. Physicians who have
      known the patient over time should rely more on their own knowledge of the
      patient's needs and preferences, seek the input of others, and openly take the
      lead in the decision-making process.

PMID- 22463802
TI  - Evaluation of resistive index by color Doppler imaging of orbital arteries in
      type II diabetes mellitus patients with microalbuminuria.
AB  - OBJECTIVE: Resistive index (RI) is an indirect measurement of blood flow
      resistance that can be used to evaluate vascular damage in ophthalmologic
      diseases. The purpose of this study was to evaluate the association between RI
      values of orbital arteries by using the color Doppler imaging (CDI) in type II
      diabetes mellitus (DM) patients with microalbuminuria. PATIENTS AND METHODS: We
      evaluated 91 type II DM patients with microalbuminuria and 27 healthy subjects.
      The DM patients with microalbuminuria were grouped into two: group 1 consisted of
      patients with retinopathy (n = 51) and group 2 consisted of patients without
      retinopathy (n = 40). Healthy subjects constituted group 3 (n = 27). The mean RI
      values of ophthalmic artery (OA), central retinal artery (CRA), and posterior
      ciliary artery (PCA) were measured using CDI. RESULTS: Compared to diabetic group
      2, group 1 had significantly higher mean RIs of OA, CRA, PCA, and HbA1c levels (p
      < 0.001 for all). Besides, there were no statistical differences in mean RIs of
      OA, CRA, and PCA between the control group and group 2 (p = 1.0; p = 0.44; p =
      0.67, respectively). Mean RIs of OA and PCA were significantly correlated with
      age in group 1 (r = 0.549, p < 0.001; r = 0.407, p = 0.003, respectively). Mean
      RI of CRA was significantly correlated with the duration of diabetes and age in
      group 1 (r = 0.296, p = 0.035; r = 0.486, p < 0.001, respectively). CONCLUSION:
      Our study indicates that RI might be a useful marker for early diagnosis and
      follow-up of diabetic retinopathy, and orbital RI assessment would be beneficial
      for diabetic patients with retinopathy.

PMID- 22463803
TI  - Myocilin, a component of a membrane-associated protein complex driven by a
      homologous Q-SNARE domain.
AB  - Myocilin is a widely expressed protein with no known function; however, mutations
      in myocilin appear to manifest uniquely as ocular hypertension and the blinding
      disease of glaucoma. Using the protein homology/analogy recognition engine
      (Phyre), we find that the olfactomedin domain of myocilin is similar in sequence
      motif and structure to a six-blade, kelch repeat motif based on the known crystal
      structures of such proteins. Additionally, using sequence analysis, we identify a
      coiled-coil segment of myocilin with homology to human Q-SNARE proteins (inset).
      Using COS-7 cells expressing full-length human myocilin and a version lacking the
      C-terminal olfactomedin domain, we identified a membrane-associated protein
      complex containing myocilin by hydrodynamic analysis. The myocilin construct that
      included the coiled-coil but lacked the olfactomedin domain formed complexes
      similar to the full-length protein, indicating that the coiled-coil domain of
      myocilin is sufficient for myocilin binding to the large detergent-resistant
      complex. In human retina and retinal pigment epithelium, which express myocilin,
      we detected the protein in a large, sodium dodecyl sulfate-resistant, membrane
      associated complex. We characterized myocilin in human tissues as either a 15 S
      complex with an M(r) of 405000-440000 yielding a slightly elongated globular
      shape similar to that of known SNARE complexes or a 6.4 S dimer with an M(r) of
      108000. By identifying the Q-SNARE homology within the second coil of myocilin
      and documenting its participation in a SNARE-like complex, we provide evidence of
      a SNARE domain-containing protein associated with a human disease.

PMID- 22463804
TI  - Validation of diagnostic accuracy using digital slides in routine histopathology.
AB  - BACKGROUND: Robust hardware and software tools have been developed in digital
      microscopy during the past years for pathologists. Reports have been advocated
      the reliability of digital slides in routine diagnostics. We have designed a
      retrospective, comparative study to evaluate the scanning properties and digital
      slide based diagnostic accuracy. METHODS: 8 pathologists reevaluated 306 randomly
      selected cases from our archives. The slides were scanned with a 20* Plan
      Apochromat objective, using a 3-chip Hitachi camera, resulting 0.465 MUm/pixel
      resolution. Slide management was supported with dedicated Data Base and Viewer
      software tools. Pathologists used their office PCs for evaluation and reached the
      digital slides via intranet connection. The diagnostic coherency and uncertainty
      related to digital slides and scanning quality were analyzed. RESULTS: Good to
      excellent image quality of slides was recorded in 96%. In half of the critical 61
      digital slides, poor image quality was related to section folds or floatings. In
      88.2% of the studied cases the digital diagnoses were in full agreement with the
      consensus. Out of the overall 36 incoherent cases, 7 (2.3%) were graded relevant
      without any recorded uncertainty by the pathologist. Excluding the non-field
      specific cases from each pathologist's record this ratio was 1.76% of all cases.
      CONCLUSIONS: Our results revealed that: 1) digital slide based histopathological
      diagnoses can be highly coherent with those using optical microscopy; 2) the
      competency of pathologists is a factor more important than the quality of digital
      slide; 3) poor digital slide quality do not endanger patient safety as these
      errors are recognizable by the pathologist and further actions for correction
      could be taken. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1913324336747310.

PMID- 22463805
TI  - High prevalence of leptin and melanocortin-4 receptor gene mutations in children
      with severe obesity from Pakistani consanguineous families.
AB  - Recessive or co-dominant single-gene mutations disrupting leptin melanocortin
      pathway cause severe obesity and hyperphagia. Since Pakistan has a very high rate
      of consanguinity, therefore, a significantly higher incidence of monogenic
      obesity is expected in its population. We have assessed the incidence of LEP and
      MC4R mutations and associated hormonal profiles, in a cohort of randomly selected
      Pakistani children with early onset of severe obesity. Sixty two unrelated
      children of consanguineous parents, with a weight-for-age percentile >97 were
      recruited in the study. Screening for mutations in the coding regions of LEP and
      MC4R was performed by direct sequencing. Serum hormone concentrations were
      determined by immunoassay. LEP mutations were found in 16.1% of the probands. Of
      these, 9 probands carried the homozygous frameshift mutation, G133_VfsX14,
      whereas one patient had a homozygous mutation involving deletion of 3 base pairs,
      (I35del). In these probands, leptin levels were very low or undetectable and
      insulin levels were increased in 33%. Homozygous MC4R mutations, M161T and I316S,
      identified separately in 2 subjects (3.2%), were associated with severe obesity,
      hyperphagia, hyperleptinemia and hyperinsulinemia. The heterozygous M161T sibling
      had normal body weight and hormone levels and the parents were only mildly
      overweight. Based on genetic analysis of LEP and MC4R genes only, we elucidated
      genetic causality of severe obesity in 20% of our patients confirming high
      prevalence of monogenic form of obesity in this consanguineous population. Co
      dominancy of MC4R is exacerbated in this group with non-penetrance of obesity in
      heterozygous loss-of-function MC4R mutation carriers. The sub-ethnic specificity
      of LEP mutation, G133_VfsX14, suggests a founder effect.

PMID- 22463806
TI  - The double burden of malnutrition and cardiometabolic risk widens the gender and
      socio-economic health gap: a study among adults in Burkina Faso (West Africa).
AB  - OBJECTIVE: To document the double burden of malnutrition and cardiometabolic risk
      factors (CMRF) in adults and its occurrence according to different
      sociodemographic parameters. DESIGN: Population-based cross-sectional
      observational study. We first randomly selected 330 households stratified by
      tertile of the income levels proxy as low, middle and high income. SETTING:
      Northern district of Ouagadougou, the capital city of Burkina Faso. SUBJECTS: In
      each income stratum, 110 individuals aged 25-60 years and who had lived
      permanently in Ouagadougou for at least 6 months were randomly selected, followed
      with collection of anthropometric, socio-economic and clinical data, and blood
      samples. RESULTS: The overall obesity/overweight prevalence was 24.2 % and it was
      twice as high in women as in men (34.1 % v. 15.5 %, P < 0.001). Hypertension,
      hyperglycaemia and low HDL cholesterol prevalence was 21.9 %, 22.3 % and 30.0 %,
      respectively, without gender difference. The prevalence of the metabolic syndrome
      was 10.3 %. Iron depletion and vitamin A deficiency affected 15.7 % and 25.7 % of
      participants, respectively, with higher rates in women. Coexistence of at least
      one nutritional deficiency and one CMRF was observed in 23.5 % of participants,
      and this 'double burden' was significantly higher in women than in men (30.4 % v.
      16.1 %, P = 0.008) and in the low income group. CONCLUSIONS: CMRF are becoming a
      leading nutritional problem in adults of Ouagadougou, while nutritional
      deficiencies persist. The double nutritional burden exacerbates health inequities
      and calls for action addressing both malnutrition and nutrition-related chronic
      diseases.

PMID- 22463807
TI  - Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are
      neuroprotective on cultured and mast cell co-cultured rat myenteric neurons.
AB  - BACKGROUND: Neuropathy is believed to be a common feature of functional and
      inflammatory intestinal diseases. Vasoactive intestinal peptide (VIP) is an
      acknowledged neuroprotective agent in peripheral, including enteric, and central
      neurons. The proglucagon-like hormones glucagon-like peptide 1 and 2 (GLP1 and
      GLP2) belong to the secretin/glucagon/VIP superfamily of peptides and GLP1 and
      GLP2 receptors are expressed in enteric neurons. Possible neuroprotective effects
      of these peptides were investigated in the present study. METHODS: GLP1, GLP2 and
      VIP were added to cultured myenteric neurons from rat small intestine or to co
      cultures of myenteric neurons and rat peritoneal mast cells. Receptor selectivity
      was tested by the simultaneous presence of a GLP1 receptor antagonist (exendin (9
      39) amide) or a VIP receptor antagonist (hybrid of neurotensin 6-11 and VIP 7
      28). Neuronal survival was examined using immunocytochemistry and cell counting.
      RESULTS: GLP1, GLP2 and VIP significantly and concentration-dependently enhanced
      neuronal survival. In addition the peptides efficiently counteracted mast cell
      induced neuronal cell death in a concentration-dependent manner. Exendin(9
      39)amide reversed GLP1-induced neuroprotection while GLP2- and VIP-induced
      enhanced neuronal survival were unaffected. The VIP receptor antagonist reversed
      GLP1- and VIP-induced neuroprotection while the GLP2-induced effect on neuronal
      survival was unaffected. CONCLUSIONS: By activating separate receptors VIP, GLP1
      and GLP2 elicit neuroprotective effects on rat myenteric neurons cultured with or
      without mast cells. This implies a powerful therapeutic potential of these
      peptides in enteric neuropathies with a broad spectrum of applications from
      autoimmunity to functional disorders.

PMID- 22463808
TI  - Rhizobium nepotum sp. nov. isolated from tumors on different plant species.
AB  - Five Gram-negative, rod-shaped, non-spore-forming bacteria were isolated from
      galls on different plant species in Hungary: strain 39/7(T) from Prunus
      cerasifera Myrobalan, strain 0 from grapevine var. Ezerjo, strain 7/1 from
      raspberry var. Findus and in Poland, strain C3.4.1 from Colt rootstock (Prunus
      avium * Prunus pseudocerasus) and strain CP17.2.2 from Prunus avium. Only one of
      these isolates, strain 0, is able to cause crown gall on different plant species.
      On the basis of 16S rRNA gene sequence similarity, the strains cluster together
      and belong to the genus Rhizobium and their closest relative is Rhizobium
      radiobacter (99.1%). Phylogenetic analysis of the novel strains using
      housekeeping genes atpD, glnA, gyrB, recA and rpoB revealed their distinct
      position separate from other known Rhizobium species and confirmed their relation
      to Rhizobium radiobacter. The major cellular fatty acids are 18:1 w7c, 16:0, 16:0
      3OH, summed feature 2 (comprising 12:0 aldehyde, 16:1 iso I and/or 14:0 3OH) and
      summed feature 3 (comprising 16:1 w7c and/or 15 iso 2OH). DNA-DNA hybridization
      of strain 39/7(T) with the type strain of R. radiobacter LMG 140(T) revealed 45%
      DNA-DNA hybridization. Phenotypic and physiological properties differentiate the
      novel isolates from other closely related species. On the basis of the results
      obtained, the five isolates are considered to represent a novel species of the
      genus Rhizobium, for which the name Rhizobium nepotum sp. nov. (type strain
      39/7(T)=LMG 26435(T)=CFBP 7436(T)) is proposed.

PMID- 22463810
TI  - Prenatal diagnosis of trisomy 18: report of 76 cases in a mainland Chinese
      hospital.

PMID- 22463811
TI  - Urgent superficial temporal artery to middle cerebral artery bypass shortly after
      intravenous rt-PA.
AB  - Whether to provide surgical intervention within 24 hours of intravenous
      recombinant tissue plasminogen activator (rt-PA) treatment is a subject of
      controversy. In this study, we report a case in which neurological deterioration
      was prevented by urgent bypass surgery performed shortly after rt-PA treatment.

PMID- 22463809
TI  - Genetic diversity, community structure and distribution of rhizobia in the root
      nodules of Caragana spp. from arid and semi-arid alkaline deserts, in the north
      of China.
AB  - The genetic diversity of 88 Caragana nodule rhizobial isolates, collected from
      arid and semi-arid alkaline sandy soils in the north of China, was assessed by
      PCR-RFLP of the 16S rRNA gene and the 16S-23S IGS, as well as the phylogenies of
      housekeeping genes (atpD, glnII and recA) and symbiotic genes (nodC and nifH). Of
      the 88 strains, 69 were placed in the genus Mesorhizobium, 16 in Rhizobium and 3
      in Bradyrhizobium. Mesorhizobium amorphae, Mesorhizobium septentrionale,
      Mesorhizobium temperatum and Rhizobium yanglingense were the four predominant
      microsymbionts associated with Caragana spp. in the surveyed regions, and M.
      septentrionale was widely distributed among the sampling sites. Phylogenies of
      nodC and nifH genes showed that two kinds of symbiotic genes existed,
      corresponding to Mesorhizobium and Rhizobium, respectively. Available phosphorous
      (P) and potassium (K) contents were the main soil factors correlated with the
      distribution of these rhizobia in the sampling regions. Positive correlations
      between the available higher P content/lower K content and the dominance of
      Mesorhizobium species (M. temperatum, M. amorphae and M. septentrionale), and
      between the lower P content/higher K content and the dominance of R. yanglingense
      were found.

PMID- 22463812
TI  - Primary cranial vault lymphoma with brain infiltration: case report and review of
      the literature.
AB  - Primary cranial vault lymphomas (PCVL) are extremely rare tumours. An extensive
      review of the literature shows that only 26 previous PCVL were reported while
      only four presented with cortex infiltration. We present a singular case of a 74
      year-old woman with a voluminous painful mass lesion of the right temporal scalp.
      Preoperative neuroradiological assessment showed a lesion involving the scalp,
      the cranial vault and the subdural space; underneath, a cerebral oedema suggested
      brain infiltration. The absence of any neurological signs despite brain
      infiltration makes this case exceptional. The preoperative diagnostic hypothesis
      was infiltrating meningioma, and a surgical excision was scheduled. A radical
      removal of the lesion was obtained, but the histopathological result was
      unexpectedly large B-cell non-Hodgkin lymphoma. Further investigations failed to
      identify pathology elsewhere confirming the diagnosis of PCVL. Postoperative
      radio and chemotherapy were administered. The patient is free from signs of
      disease recurrence at a 2-year follow-up. Radiological features are debated with
      the aim to stress the possible differential diagnosis, and prognostic factors are
      discussed. Even if an accepted therapeutic algorithm is far from being defined
      for these extremely rare tumours, we suggest that radical surgical removal
      associated with radio and chemotherapy could be the best choice in these
      particular cases.

PMID- 22463813
TI  - Intraosseous schwannoma with ancient change on the lumbar spine.
AB  - A 65-year-old male was admitted for progressive lower back pain. The preoperative
      revealed an osteolytic expansile mass with a sclerotic margin involving the right
      lamina and pedicle of L2. The histopathology revealed an ancient schwannoma. We
      report a rare case of an intraosseous ancient schwannoma involving lumbar
      vertebra along with its imaging findings and surgical aspects.

PMID- 22463814
TI  - The utility of myelography in lumbar canal stenosis.

PMID- 22463816
TI  - Hahn-echo decay for exchange-coupled nuclear spins in solids.
AB  - In this paper we present a simple model to calculate the Hahn-echo decay of the
      exchange-coupled nuclear spins in solids. Satisfactory agreement between the
      calculated and experimentally observed echo decay of the exchange-coupled spins
      of T203l and T205l isotopes in thallium chloride TlCl and thallium tantalum
      sulfide TlTaS(3) is obtained.

PMID- 22463815
TI  - Spectrophotometric calibration of pH electrodes in seawater using purified m
      cresol purple.
AB  - This work examines the use of purified meta-cresol purple (mCP) for direct
      spectrophotometric calibration of glass pH electrodes in seawater. The procedures
      used in this investigation allow for simple, inexpensive electrode calibrations
      over salinities of 20-40 and temperatures of 278.15-308.15 K without preparation
      of synthetic Tris seawater buffers. The optimal pH range is ~7.0-8.1.
      Spectrophotometric calibrations enable straightforward, quantitative distinctions
      between Nernstian and non-Nernstian electrode behavior. For the electrodes
      examined in this study, both types of behavior were observed. Furthermore,
      calibrations performed in natural seawater allow direct determination of the
      influence of salinity on electrode performance. The procedures developed in this
      study account for salinity-induced variations in liquid junction potentials that,
      if not taken into account, would create pH inconsistencies of 0.028 over a 10
      unit change in salinity. Spectrophotometric calibration can also be used to
      expeditiously determine the intercept potential (i.e., the potential
      corresponding to pH 0) of an electrode that has reliably demonstrated Nernstian
      behavior. Titrations to ascertain Nernstian behavior and salinity effects can be
      undertaken relatively infrequently (~weekly to monthly). One-point determinations
      of intercept potential should be undertaken frequently (~daily) to monitor for
      stable electrode behavior and ensure accurate potentiometric pH determinations.

PMID- 22463817
TI  - Proteins of Leishmania (Viannia) shawi confer protection associated with Th1
      immune response and memory generation.
AB  - BACKGROUND: Leishmania (Viannia) shawi parasite was first characterized in 1989.
      Recently the protective effects of soluble leishmanial antigen (SLA) from L. (V.)
      shawi promastigotes were demonstrated using BALB/c mice, the susceptibility model
      for this parasite. In order to identify protective fractions, SLA was
      fractionated by reverse phase HPLC and five antigenic fractions were obtained.
      METHODS: F1 fraction was purified from L. (V.) shawi parasite extract by reverse
      phase HPLC. BALB/c mice were immunized once a week for two consecutive weeks by
      subcutaneous routes in the rump, using 25 MUg of F1. After 1 and 16 weeks of last
      immunization, groups were challenged in the footpad with L. (V.) shawi
      promastigotes. After 2 months, those same mice were sacrificed and parasite
      burden, cellular and humoral immune responses were evaluated. RESULTS: The F1
      fraction induced a high degree of protection associated with an increase in IFN
      gamma, a decrease in IL-4, increased cell proliferation and activation of CD8+T
      lymphocytes. Long-term protection was acquired in F1-immunized mice, associated
      with increased CD4+ central memory T lymphocytes and activation of both CD4+ and
      CD8+ T cells. In addition, F1-immunized groups showed an increase in IgG2a
      levels. CONCLUSIONS: The inductor capability of antigens to generate memory
      lymphocytes that can proliferate and secrete beneficial cytokines upon infection
      could be an important factor in the development of vaccine candidates against
      American Tegumentary Leishmaniasis.

PMID- 22463818
TI  - M4 muscarinic receptor knockout mice display abnormal social behavior and
      decreased prepulse inhibition.
AB  - BACKGROUND: In the central nervous system (CNS), the muscarinic system plays key
      roles in learning and memory, as well as in the regulation of many sensory,
      motor, and autonomic processes, and is thought to be involved in the
      pathophysiology of several major diseases of the CNS, such as Alzheimer's
      disease, depression, and schizophrenia. Previous studies reveal that M4
      muscarinic receptor knockout (M4R KO) mice displayed an increase in basal
      locomotor activity, an increase in sensitivity to the prepulse inhibition (PPI)
      disrupting effect of psychotomimetics, and normal basal PPI. However, other
      behaviorally significant roles of M4R remain unclear. RESULTS: In this study, to
      further investigate precise functional roles of M4R in the CNS, M4R KO mice were
      subjected to a battery of behavioral tests. M4R KO mice showed no significant
      impairments in nociception, neuromuscular strength, or motor
      coordination/learning. In open field, light/dark transition, and social
      interaction tests, consistent with previous studies, M4R KO mice displayed
      enhanced locomotor activity compared to their wild-type littermates. In the open
      field test, M4R KO mice exhibited novelty-induced locomotor hyperactivity. In the
      social interaction test, contacts between pairs of M4R KO mice lasted shorter
      than those of wild-type mice. In the sensorimotor gating test, M4R KO mice showed
      a decrease in PPI, whereas in the startle response test, in contrast to a
      previous study, M4R KO mice demonstrated normal startle response. M4R KO mice
      also displayed normal performance in the Morris water maze test. CONCLUSIONS:
      These findings indicate that M4R is involved in regulation of locomotor activity,
      social behavior, and sensorimotor gating in mice. Together with decreased PPI,
      abnormal social behavior, which was newly identified in the present study, may
      represent a behavioral abnormality related to psychiatric disorders including
      schizophrenia.

PMID- 22463819
TI  - The histone chaperone ASF1 is essential for sexual development in the filamentous
      fungus Sordaria macrospora.
AB  - Ascomycetes develop four major types of fruiting bodies that share a common
      ancestor, and a set of common core genes most likely controls this process. One
      way to identify such genes is to search for conserved expression patterns. We
      analysed microarray data of Fusarium graminearum and Sordaria macrospora,
      identifying 78 genes with similar expression patterns during fruiting body
      development. One of these genes was asf1 (anti-silencing function 1), encoding a
      predicted histone chaperone. asf1 expression is also upregulated during
      development in the distantly related ascomycete Pyronema confluens. To test
      whether asf1 plays a role in fungal development, we generated an S. macrospora
      asf1 deletion mutant. The mutant is sterile and can be complemented to fertility
      by transformation with the wild-type asf1 and its P. confluens homologue. An ASF1
      EGFP fusion protein localizes to the nucleus. By tandem-affinity
      purification/mass spectrometry as well as yeast two-hybrid analysis, we
      identified histones H3 and H4 as ASF1 interaction partners. Several developmental
      genes are dependent on asf1 for correct transcriptional expression. Deletion of
      the histone chaperone genes rtt106 and cac2 did not cause any developmental
      phenotypes. These data indicate that asf1 of S. macrospora encodes a conserved
      histone chaperone that is required for fruiting body development.

PMID- 22463820
TI  - Outcome, pathologic findings, and compliance in orbital retinoblastoma
      (International Retinoblastoma Staging System stage III) treated with neoadjuvant
      chemotherapy: a prospective study.
AB  - PURPOSE: The present study prospectively evaluated outcome, pathologic findings,
      and compliance in orbital retinoblastoma patients (International Retinoblastoma
      Staging System [IRSS] stage III). DESIGN: Prospective study and case series.
      PARTICIPANTS: Twenty-eight consecutive IRSS stage III retinoblastoma patients
      were enrolled prospectively in the study after ethics committee approval and
      written informed consent. METHODS: Planned therapy for patients included
      treatment with a uniform protocol consisting of neoadjuvant chemotherapy followed
      by enucleation, adjuvant radiotherapy, and chemotherapy. Prospective computerized
      data entry and telephone contact were undertaken to improve compliance, a major
      issue in treatment of orbital retinoblastoma. MAIN OUTCOME MEASURES: Event-free
      survival (EFS) and overall survival (OS) were calculated using Kaplan-Meier
      survival analysis. The difference between groups was analyzed using the log-rank
      test. RESULTS: Median follow-up was 14.75 months (range, 2.23-26.3 months). The
      OS for all patients was 40.4% and the EFS was 33.33% at a follow-up of 26.3
      months. The median EFS and OS were 10.37 months and 15.73 months, respectively.
      At baseline, bilateral retinoblastoma predicted inferior EFS (P = 0.0006) and OS
      (P = 0.0081). Twenty-two of 28 patients underwent enucleation, and viable tumor
      was present in 21 of 22 enucleated specimens (95%). Neoadjuvant chemotherapy
      prevented orbital exenterations. Presence of tumor in the cut end of the optic
      nerve significantly correlated with inferior EFS (P = 0.012) and OS (P = 0.0098).
      Central nervous system metastasis was the most common site of relapse and death.
      The overall rate of compliance with treatment was 67.8% (19/28), which was twice
      the compliance rate at the authors' center before initiation of the present
      study. CONCLUSIONS: There is a paucity of information in the literature on
      outcomes and pathologic findings after neoadjuvant chemotherapy in IRSS stage III
      retinoblastoma treated with a uniform treatment protocol, and as far as the
      authors are aware, there has been no prospective study. Neoadjuvant chemotherapy
      was able to avoid exenteration in all operated patients; however, residual viable
      tumor was present in 95% of enucleated specimens. Bilaterality and tumor in the
      optic nerve cut end after neoadjuvant chemotherapy were associated with inferior
      outcome. Compliance could be improved with computerized data entry and regular
      telephone contact.

PMID- 22463821
TI  - Clinical features and presentation of infectious scleritis from herpes viruses: a
      report of 35 cases.
AB  - PURPOSE: To describe clinical features and presentation of infectious scleritis
      resulting from herpes viruses. DESIGN: Retrospective case series. PARTICIPANTS:
      Thirty-five patients out of 500 with scleritis. METHODS: We reviewed the
      electronic health records of 500 patients with scleritis, 35 of whom were
      diagnosed with herpes virus infection, seen at 2 tertiary referral centers. We
      studied the clinical features and ocular complications of this subset of patient
      with scleritis. MAIN OUTCOME MEASURES: Correlation between classification,
      severity, and symptoms (i.e., pain) and diagnosis of herpetic-associated
      scleritis. Vision loss, presence of associated uveitis, keratitis, glaucoma, or
      systemic disease were documented over the follow-up period. Other outcome
      measures included epidemiologic data: age, gender, laterality, visual acuity,
      duration of symptoms, and underlying systemic or ocular diseases. RESULTS: Of 500
      patients with scleritis, 47 (9.4%) had an underlying infectious cause. Thirty
      five (74.4%) of these were diagnosed with herpes virus infection, 5 (10.6%) with
      tuberculosis, and the remaining 7 (14.8%) with other infectious disease. Patients
      with herpes-associated scleritis were analyzed as a group and then compared with
      those with idiopathic scleritis. Most patients with herpetic scleritis presented
      with acute (85.7%) and unilateral (80%) scleral inflammation. Pain was moderate
      or severe in 68.6% of the patients. The most common type of scleritis was diffuse
      anterior in 80% (n = 28), followed by nodular anterior 11.4% (n = 4), and
      necrotizing in 8.6% (n = 3). Necrotizing anterior scleritis was more commonly
      seen in patients with herpetic scleritis versus patients with idiopathic disease
      (8.6% vs 1.2%; P<0.05). Unilaterality was also more common in herpetic scleritis
      (80%) than in idiopathic disease (56.7%; P<0.05). Vision loss was significantly
      greater in herpetic than idiopathic scleritis (34.3% vs 11.5%; P<0.001).
      CONCLUSIONS: The association between scleritis and infectious disease may be
      higher than previously reported by other series. Herpes viruses account for 7% of
      all scleritis cases and its diagnosis may be challenging when there is not a
      classically diagnostic clinical picture. We present the observed clinical
      features of herpetic scleritis and describe the clinical differences at
      presentation between patients with idiopathic scleritis and those with herpes
      infection.

PMID- 22463822
TI  - Assay sensitivity in clinical trials with chronic pain patients.

PMID- 22463823
TI  - What can we learn from twin studies of pain and analgesia?

PMID- 22463824
TI  - Why is my patient anemic?
AB  - Anemia is a decreased number of circulating red blood cells and is a common
      medical condition faced in clinical practice. Anemia is caused by loss of red
      blood cells, destruction of red blood cells, decreased production of red blood
      cells, or a combination of these processes. Through a clinical history, physical
      examination, and laboratory evaluation the provider must identify the process by
      which the patient is anemic. Often the cause of anemia is straightforward;
      however, the cause can be challenging, requiring a thorough knowledge of both
      hematology and general medicine.

PMID- 22463825
TI  - Why does my patient have thrombocytopenia?
AB  - Thrombocytopenia, usually defined as a platelet count of less than 150,000/MUL,
      is a common reason for a hematology consult in both the inpatient and outpatient
      setting. In most patients, the cause of the thrombocytopenia can be identified
      and treated. This article reviews the clinical approach to the patient with
      thrombocytopenia, the mechanisms that underlie it, and the laboratory tests
      available to investigate it. A practical approach to the investigation and
      management of thrombocytopenia in the clinical settings commonly encountered by
      the hematology consultant is then described.

PMID- 22463826
TI  - Why is my patient neutropenic?
AB  - Neutropenia is a common reason for hematology consultations in the inpatient and
      outpatient settings and is defined as an absolute neutrophil count less than 1500
      cells/MUL. Neutropenia varies in severity, with more profound neutropenia being
      associated with higher rates of infections and infection-related deaths. The
      causes for neutropenia are diverse and include congenital and acquired conditions
      (ie, autoimmune, drugs, infection, and malignancy). This article outlines the
      most common causes of neutropenia and discusses differential diagnoses, treatment
      modalities, and the mechanisms by which neutropenia occurs.

PMID- 22463827
TI  - Why does my patient have erythrocytosis?
AB  - Primary polycythemias are the result of intrinsic abnormalities of the
      hematopoietic progenitors that lead to constitutive overproduction of red cells
      accompanied by low erythropoietin (EPO) levels. Secondary polycythemias are
      caused by conditions resulting in increased EPO production. Polycythemia vera
      (PV) is a primary polycythemia, and is a chronic clonal progressive
      myeloproliferative neoplasm. A single recurrent point mutation in the
      pseudokinase domain of JAK2 molecule (JAK2(V617F)) is present in >95% of patients
      with PV. The goal of therapy in PV is to normalize blood counts to minimize the
      risk of thrombotic events.

PMID- 22463828
TI  - Why does my patient have thrombocytosis?
AB  - Thrombocytosis is a common clinical problem frequently encountered during routine
      evaluation. The diagnostic workup entails a step-by-step approach, which allows
      for an accurate assessment of the underlying cause. A thorough clinical history
      and physical examination may help differentiate thrombocytosis secondary to a
      reactive process versus an underlying clonal proliferation process. Once
      essential thrombocytosis is evident, relevant laboratory evaluation for an
      ongoing myeloproliferative disorder is paramount. Various treatment modalities
      have been proven to be beneficial. With further scientific investigation
      underway, molecular therapies may soon be cornerstones of therapy in essential
      thrombocytosis.

PMID- 22463829
TI  - Why does my patient have leukocytosis?
AB  - Leukocytosis is one of the most common laboratory abnormalities in medicine, and
      one of the most frequent reasons for hematologic consultation. Effective
      evaluation of leukocytosis requires an attentive history, careful physical
      examination, meticulous review of the complete blood count and peripheral blood
      smear, judicious application of laboratory and radiologic testing, and thoughtful
      analysis. Definitive diagnosis may require bone marrow aspiration and biopsy,
      imaging studies, and specialized molecular tests. The differential diagnosis of
      leukocytosis includes physiologic responses to a broad range of infectious and
      inflammatory processes, as well as numerous primary hematologic disorders such as
      leukemias, lymphomas, and myeloproliferative neoplasms.

PMID- 22463830
TI  - Why is my patient bleeding or bruising?
AB  - The evaluation of a patient presenting with bleeding symptoms is challenging.
      Bleeding symptoms are frequently reported by a normal population, and overlap
      significantly with bleeding disorders, such as type 1 Von Willebrand disease. The
      history is subjective; bleeding assessment tools significantly facilitate an
      accurate quantification of bleeding severity. The differential diagnosis is
      broad, ranging from defects in primary hemostasis, coagulation deficiencies, to
      connective tissue disorders. Finally, despite significant clinical evidence of
      abnormal bleeding, many patients will have not an identifiable disorder. Clinical
      management of bleeding disorders is highly individualized and focuses on the
      particular symptoms experienced by the patient.

PMID- 22463831
TI  - Venous thromboembolism overview.
AB  - This article gives a general overview of venous thromboembolism (VTE).
      Pathophysiology, presentation, diagnosis, and initial management of VTE are
      briefly reviewed. More difficult management problems are reviewed in greater
      depth, including duration of anticoagulation, treatment of superficial venous
      thrombosis, and controversies surrounding bridging therapy, with a brief review
      of currently available new oral anticoagulants.

PMID- 22463832
TI  - Does my patient have a life- or limb-threatening thrombocytopenia?
AB  - The diagnosis and management of severe thrombocytopenias can be difficult, but is
      necessary to avoid significant morbidity and mortality. The causes of severe
      thrombocytopenias, often with a platelet count of less than 10 * 10(9)/L, include
      heparin-induced thrombocytopenia, the thrombotic microangiopathies, the
      catastrophic antiphospholipid syndrome, preeclampsia/HELLP, and posttransfusion
      purpura. This review provides a brief overview of the key clinical features of
      each of these major clinical entities, and strategies for their diagnostic workup
      and therapeutic management.

PMID- 22463834
TI  - Why does my patient have lymphadenopathy or splenomegaly?
AB  - Lymph node or spleen enlargement may be innocent or the first sign of a serious
      disorder. Lymphadenopathy and splenomegaly can be found in symptomatic or
      asymptomatic patients. Lymph node enlargement in a single region or multiple
      sites can be seen in various diseases, including infections, noninfectious
      inflammatory conditions, or malignancies; a similar differential diagnosis
      applies to splenomegaly, but splenomegaly can also be caused by vascular
      abnormalities and hemolysis. Frequently, lymphadenopathy is detected incidentally
      during screening examinations or imaging procedures. This review focuses on
      causes of lymphadenopathy and splenomegaly and an appropriate diagnostic approach
      to patients with lymphadenopathy or splenomegaly.

PMID- 22463835
TI  - Special hematologic issues in the pregnant patient.
AB  - Evaluation and treatment of hematologic disorders in pregnancy requires an
      understanding of normal physiologic changes during pregnancy. Hematologic
      disorders may be caused by preexisting conditions, normal physiologic changes, or
      can be acquired. A multidisciplinary approach is often necessary for monitoring
      and treatment of both the mother and the fetus. In general, outcomes are good for
      both the mother and the fetus.

PMID- 22463833
TI  - Does my patient with a serum monoclonal spike have multiple myeloma?
AB  - A monoclonal spike on serum protein electrophoresis is a frequent finding in the
      general population and pathognomonic of a plasma cell dyscrasia. In otherwise
      healthy individuals, it is diagnostic of two asymptomatic, premalignant
      conditions called monoclonal gammopathy of undetermined significance (MGUS) and
      smoldering multiple myeloma (SMM) which carry a lifelong risk of progression to
      multiple myeloma (MM) or related malignancy. This article discusses the criteria
      for diagnosis of MGUS, SMM, and MM; current recommendations for follow-up and
      risk factors for progression to MM of patients with MGUS and SMM; and diagnostic
      evaluation of suspected MM transformation.

PMID- 22463836
TI  - Preface. Consultative hematology.

PMID- 22463837
TI  - Prognostic value of late heart rate recovery after treadmill exercise.
AB  - Recovery from exercise can be divided into an early, rapid period and a late,
      slower period. Although early heart rate (HR) recovery 1 minute after treadmill
      exercise independently predicts survival, the prognostic value of late HR
      recovery has not been well studied. The aim of this study was to evaluate the
      independent prognostic value of late HR recovery for all-cause mortality. A total
      of 2,082 patients referred to the nuclear cardiology laboratory of an urban
      academic medical center for treadmill exercise with imaging from August 1998 to
      December 2003 were followed for all-cause mortality. During 9.9 +/- 1.5 years of
      follow-up, 196 deaths (9%) occurred. To avoid overlap with early HR recovery or
      the baseline HR, late HR recovery was defined as the percentage of the cycle
      length change between rest and peak exercise that had been recovered after 5
      minutes. Lower values represent impaired recovery, by analogy with 1-minute HR
      recovery. Impaired late HR recovery was a significant univariate predictor of all
      cause mortality (hazard ratio 0.28 per percentage, 95% confidence interval 0.17
      to 0.46, p <0.001). It significantly improved a nested, multivariate model
      (change in chi-square 8.66, p = 0.003), including 1-minute HR recovery, with
      independent prognostic value (adjusted hazard ratio 0.58, 95% confidence interval
      0.41 to 0.84, p = 0.004). In conclusion, late HR recovery after treadmill
      exercise stress adds prognostic value for all-cause mortality to a multivariate
      model including early, 1-minute HR recovery.

PMID- 22463838
TI  - Comparison of frequency of major adverse events in patients with atrial
      fibrillation receiving bare-metal versus drug-eluting stents in their coronary
      arteries.
AB  - In patients with atrial fibrillation (AF) undergoing percutaneous coronary
      intervention with drug-eluting stent (DES) implantation, the available evidence
      from clinical trial data are inconclusive. We evaluated the safety and efficacy
      of the use of DESs versus bare-metal stents (BMSs) in a consecutive real-world
      cohort of patients with AF. Of 8,962 unselected patients with AF seen in our
      institution from 2000 through 2010, 833 (9%) had undergone percutaneous coronary
      intervention with stent implantation. BMSs were used for 678 patients (81%) and
      DESs for 155 (19%). During follow-up (median 688 days, interquartile range
      1,114), all bleeding episodes, thromboembolism, and major adverse cardiac events
      (MACEs; i.e., death, acute myocardial infarction, target lesion
      revascularization) were recorded. Incidence of MACEs was similar in the 2 groups
      as was incidence of all-cause mortality. Results remained similar even after
      adjustment for age and other confounding factors. Factors independently
      associated with an increased risk of MACEs were older age (hazard ratio 1.024,
      95% confidence interval 1.004 to 1.044, p = 0.02), implantation of stent during
      acute ST-segment elevation myocardial infarction (hazard ratio 1.81, 95%
      confidence interval 1.10 to 2.99, p = 0.02), and stent diameter (hazard ratio
      1.09, 95% confidence interval 1.01 to 1.18, p = 0.03). Implantation of DESs was
      not significantly associated with a higher risk of major bleeding and we observed
      a similar ratio of serious events at follow-up after DES compared to BMS
      implantation. In conclusion, in our cohort, systematic use of DESs does not seem
      to be justified in most patients with AF because it was not associated with any
      clear advantage compared to BMSs.

PMID- 22463839
TI  - Effects of angiotensin-converting enzyme inhibitors and/or beta blockers on the
      cardiomyopathy in Duchenne muscular dystrophy.
AB  - Cardiomyopathy is a consequence of Duchenne muscular dystrophy (DMD). Suggested
      treatments include angiotensin-converting enzyme (ACE) inhibitors and/or beta
      blockers (BBs), but few large series have been reported. We present 42 patients
      with DMD and cardiomyopathy treated with an ACE inhibitor or an ACE inhibitor
      plus a BB. Serial echocardiograms were recorded. Adequate ejection fractions
      (EFs) were obtained at initiation of therapy (EF <55%). ACE inhibitor dosage
      adjustments were made if a continued decrease in EF was noted. BB therapy was
      initiated when average heart rate on Holter monitoring exceeded 100 beats/min.
      Data were analyzed using paired t test and linear regression. Before ACE
      inhibition, patients (n = 22) demonstrated decreased EF over time (r(2) = 0.23).
      At ACE inhibitor therapy initiation, mean age was 14.1 +/- 4.6 years and mean EF
      was 44.2 +/- 6.8%. BB therapy was used in 24 of 42 patients. Mean age for the ACE
      inhibitor + BB group was 15.7 +/- 3.9 years. The 2 groups showed significant
      improvement (p <0.0001 for ACE inhibitor and ACE inhibitor plus BB) compared to
      the pretherapy group. No significant differences were noted between treatment
      groups. Patients with DMD demonstrated a gradual decrease in myocardial function.
      Treatment with ACE inhibitor or ACE inhibitor plus BB resulted in significant
      improvement compared to pretherapy. No significant difference occurred in EF
      improvement between treatment groups. In conclusion, treatment with ACE inhibitor
      or ACE inhibitor plus BB can delay progression of cardiomyopathy.

PMID- 22463840
TI  - A novel hamatometacarpal fracture-dislocation classification system based on CT
      scan.
AB  - PURPOSE: The purpose of this study was to devise a novel classification of a
      hamatometacarpal fracture-dislocation based on the preoperative computed
      tomography (CT) and plain radiography that provided more information to surgeons
      regarding appropriate treatment methods. MATERIALS AND METHODS: Twenty-one
      patients with a hamatometacarpal fracture-dislocation were enrolled in this
      study. The classification scheme devised for hamatometacarpal fracture
      dislocation is summarised as follows: type I - a simple dislocation; type IIA - a
      dislocation with the fourth metacarpal base intra-articular fracture; type IIB -
      a dislocation with a dorsal hamate fracture of less than one-third of the
      articular surface; and type III - a dislocation with a dorsal hamate fracture of
      more than one-third of the articular surface. RESULTS: Type I injury was treated
      conservatively after closed reduction. Type IIA and IIB injuries were treated by
      percutaneous K-wire fixation. Type III injury was treated by open reduction and
      internal fixation. All injuries were well managed in both clinical and
      radiographic evaluations, without apparent complications. CONCLUSION: The novel
      classification system for hamatometacarpal fracture-dislocation can be used to
      establish guidelines for appropriate treatment.

PMID- 22463842
TI  - Health impacts of air pollution: a life course approach for examining predictors
      of respiratory health in adulthood.
AB  - PURPOSE: This research applies a life course health development framework to
      examine the impacts of childhood exposure to air pollution on respiratory health
      in adulthood. METHODS: This prospective cohort study uses data collected from
      children originally studied in the 1970/1980s, including exposure to air
      pollution, indoor exposures, sociodemographic variables, and health outcomes
      data. Thirty years later, a self-administered questionnaire was used to collect
      data from adulthood on health status, occupational and residential histories,
      socioeconomic status, and lifestyle. RESULTS: Overall, 29% of respondents were
      diagnosed with at least one respiratory condition and 24% have persistent
      respiratory symptoms in adulthood. Significant neighborhood differences in
      exposure variables and adulthood health outcomes were found. Predictors of
      adulthood respiratory health include asthma diagnosis or chest illness in
      childhood, parental record of respiratory symptoms, other medical diagnosis in
      adulthood, fair/poor self-perceived health, smoking/exposure to smoking, and
      residing in a property built before 1950. Results suggest that exposure to
      ambient total suspended particulates in childhood is preventative for diagnosis
      with at least one respiratory condition in adulthood. CONCLUSION: Findings
      suggest that long-term childhood exposure to air pollution does not predict
      respiratory conditions and symptoms in adulthood. However, respiratory health in
      childhood predicts adulthood respiratory health, thus suggesting that the health
      impacts of any exposures that impact respiratory health during critical or
      sensitive times in childhood are long term.

PMID- 22463841
TI  - Education and coronary heart disease risk associations may be affected by early
      life common prior causes: a propensity matching analysis.
AB  - PURPOSE: Education is inversely associated with coronary heart disease (CHD);
      however whether this is attributable to causal effects of schooling rather than
      potential confounders existing before school entry (eg, childhood intelligence,
      childhood economic circumstances, childhood chronic illness, parental mental
      health) remains unknown. We evaluated whether education is associated with 10
      year CHD risk independent of 21 prospectively assessed childhood conditions, in
      participants ages 38-47 years. METHODS: Using linear regression analyses, we
      evaluated associations of education with 10-year CHD risk, the latter calculated
      by use of the validated Framingham risk algorithm incorporating diabetes, blood
      pressure, total and high-density lipoprotein cholesterol, smoking, age, and sex.
      Propensity score matching incorporated 21 early-life potential confounders.
      RESULTS: Regression analyses demonstrated college graduation was associated with 
      27.9% lower (95% CI, -36.2, -18.6%) 10-year CHD risk compared with <=high school
      after matching on propensity score that included age, sex and race (n = 272);
      addition of 21 early life potential confounders resulted in effect size of -13.1%
      (95% CI, -33.4, 13.4; mean n = 110). CONCLUSIONS: Participants with college
      degree had substantially lower risk of CHD (27.9%) after accounting for
      demographics; the addition of early life potential confounders resulted in a
      moderate effect size (13.1%), suggesting potential importance of early life
      factors in explaining observed associations between education and CHD risk.

PMID- 22463843
TI  - Workplace homicides among U.S. women: the role of intimate partner violence.
AB  - PURPOSE: Intimate partner violence (IPV) is an important public health issue with
      serious consequences for the workplace. Workplace homicides occurring to U.S.
      women over a 6-year period, including those perpetrated by an intimate partner,
      are described. METHODS: Workplace homicides among U.S. women from 2003 to 2008
      were categorized into type I (criminal intent), type II (customer/client), type
      III (co-worker), or type IV (personal relations) events using the Census of Fatal
      Occupational Injuries. Fatality rates were calculated and compared among
      workplace violence (WPV) types, occupations, and characteristics including
      location of homicide, type of workplace, time of day, and weapon used. RESULTS:
      Between 2003 and 2008, 648 women were feloniously killed on the job. The leading
      cause of workplace homicide for U.S. women was criminal intent, such as robbing a
      store (n = 212; 39%), followed by homicides perpetrated by a personal relation (n
      = 181; 33%). The majority of these personal relations were intimate partners (n =
      142; 78%). Over half of workplace homicides perpetrated by intimate partners
      occurred in parking lots and public buildings (n = 91; 51%). CONCLUSIONS: A large
      percentage of homicides occurring to women at work are perpetrated by intimate
      partners. WPV prevention programs should incorporate strategies to prevent and
      respond to IPV.

PMID- 22463845
TI  - Design and evaluation of polymer coated carvedilol loaded solid lipid
      nanoparticles to improve the oral bioavailability: a novel strategy to avoid
      intraduodenal administration.
AB  - Solid lipid nanoparticles are most promising delivery systems for the enhancement
      of bioavailability of highly lipophilic drugs those prone to the first pass
      metabolism. But burst release of drug from solid lipid nanoparticles in acidic
      environment such as gastric milieu precludes its usage as oral delivery system.
      Studies on SLN revealed intraduodenal administration as an alternative route for
      SLN administration. But clinically it is an inappropriate route for repeated
      administration of drugs to patients. Hence, we prepared N-carboxymethyl chitosan
      (MCC) coated carvedilol loaded SLN to protect the rapid release of carvedilol in
      acidic environment. Positively charged carvedilol loaded SLN were developed using
      monoglyceride as lipid and soya lecithin and poloxamer 188 as surfactants and
      stearylamine as charge modifier. These SLN were characterized for particle size,
      zeta potential, entrapment efficiency, crystallinity and stability studies.
      Further these SLN were coated with N-carboxymethyl chitosan and confirmed by
      change in zetapotential and X-ray Photon Spectroscopic analysis. Effect of
      polymer coating on drug release profiles were studied simulated gastric and
      intestinal fluids. Effect of polymer coating on oral bioavailability of
      carvedilol loaded SLN were studied in rats after oral administration. MCC coated
      SLN improved the bioavailability of carvedilol compared uncoated SLN after oral
      administration. Insignificant difference in bioavailability was observed compared
      to intraduodenal administration of SLN. Hence, MCC coated SLN is a novel strategy
      to avoid intrduodenal administration.

PMID- 22463844
TI  - Income inequality and cause-specific mortality during economic development.
AB  - PURPOSE: Life expectancy is strongly related to national income, whether there is
      an additional contribution of income inequality is unclear. METHODS: We used
      negative binomial regression to examine the association of neighborhood-level
      Gini, adjusted for age, sex, and income, with mortality rates in Hong Kong from
      1976 to 2006. RESULTS: The association of neighborhood Gini with all-cause
      mortality varied over time (p-value for interaction < .01). Neighborhood Gini was
      positively associated with nonmedical mortality in 1976 to 1986; incident rate
      ratio (IRR) 1.09, 95% confidence interval (95% CI) 1.02-1.16 per 0.1 change and
      in 1991 to 2006, IRR 1.24, 95% CI 1.13-1.36, adjusted for age, sex and absolute
      income. Similarly adjusted, Gini was not associated with all-cause mortality in
      1976 to 1986 (IRR 0.96, 95% CI 0.93-1.00) but was in 1991 to 2006 (IRR 1.25, 95%
      CI 1.20-1.29), when Gini was also positively associated with death from
      cardiovascular diseases, respiratory diseases and some cancers. CONCLUSIONS:
      Independent of income, income inequality was positively associated with
      nonmedical mortality rates at a low level of spatial aggregation, indicating the
      consistent harms of social disharmony. However, the impact on medical mortality
      was less consistent, suggesting the relevance of contextual factors.

PMID- 22463846
TI  - Shape-directing role of cetyltrimethylammonium bromide in the green synthesis of
      Ag-nanoparticles using Neem (Azadirachta indica) leaf extract.
AB  - The shape-directing role of cetyltrimethylammonium bromide, CTAB, is reported to
      the green synthesis of Ag-nanoparticles for the first time using Neem
      (Azadirachta indica) leaf extract. UV-vis spectroscopy, transmission electron
      microscopy (TEM), and selected area electron diffraction (SAED) patterns were
      used to monitor the growth kinetics, morphology and crystalline nature of Ag
      nanoparticles, respectively. It was observed that the growths of Ag-nanoparticles
      are stopped within 40 min of reaction time. The Ag-nanoparticles are
      polydispersed spherical and exhibiting an interesting triangle, flat, plate-like
      hexagonal and some irregular morphology in presence of different [CTAB].
      Hexagonal particles aggregated in a systematic manor, leads to produce a fine
      tiles-like arrangement of Ag-nanoparticles with dimensions between 10 and 37 nm.
      The nature of reaction-time curves to the reduction of Ag(+) ions by Neem leaf
      extract are much different than those observed by us in our earlier studies using
      different bio-reductants.

PMID- 22463847
TI  - [How the patients on sick leave assess the Medical Inspector: The Institut Catala
      d'Avaluacions Mediques (ICAM) experience in Catalonia].
AB  - OBJECTIVE: To analyse the patient perception of the medical inspector, and to
      examine whether this perception is related with the outcome of the medical
      report. MATERIAL AND METHODS: A cross-sectional study based on telephone
      interviews with a random sample of patients visited in Catalonia in 2010 for
      temporary (TSL) or permanent (PSL) sick leave. The study was conducted in
      November 2011. A stratified sample considering the time from the consultation and
      province where patients were visited was used. The scale was assessed by
      Intraclass Correlation coefficient (0.93, 95% CI; 0.92-0.94) and testing with the
      Spearman-Brown split-half coefficient (0.93). RESULTS: A total of 609 patients
      were surveyed. A majority of them (400; 65.7%) had a positive opinion of the
      medical inspector. When PSL was denied, the assessment was worse (P=.002), this
      was different when TSL was cancelled. Patients who did not continue in PSL stated
      that doctor's decisions were determined by non-medical interests, and not
      oriented to the defence of the patient's rights (odds ratio 2.8, 95% CI; 1.7 to
      4.8). When the perceptions were negative, patients focus their criticism on the
      role of medical inspector (P<.001), and not about the organisational aspects.
      CONCLUSIONS: When inspectors cancel PSL, patient's perception is strongly
      associated with a negative assessment of their performance, capacity and
      independence of the physician. This is not so in the case of TSL.

PMID- 22463848
TI  - [Clinical practice variations: quality of prescription of proton pump
      inhibitors].

PMID- 22463849
TI  - [Clarity of recommendations for patients in the hospital discharge report].
AB  - BACKGROUND: Recommendations for patients (RP) are one of the key parts of the
      hospital discharge report (HDR). The objective was to study the frequency of RP
      in the HDR of different specialties and the proportion of them considered to be
      easy to understand. MATERIAL AND METHOD: Observational and cross-sectional study.
      SETTING: General acute care hospital. INTERVENTIONS: Review of a sample of HDR,
      analysis of the frequency and types of PR based on their content and clarity.
      RESULTS: A total of 840 HDR and 2,097 PR were analysed with an average of 2.5 RP
      per report. The most common RP referred to the patient follow-up (46% of total),
      followed by specific recommendations for the days immediately following discharge
      (37%), with only 16% related to lifestyle. Reports by surgical specialties
      contained 3.2 RP compared to 2.3 in medical specialties. The large majority
      (90.3%) of the RP were considered clear to understand for a standard patient.
      CONCLUSIONS: The HDR analysed contained few RP, in particular those related to
      lifestyles. A substantial proportion of the RP were not expressed with enough
      clarity.

PMID- 22463850
TI  - Long-term transformation and fate of manufactured ag nanoparticles in a simulated
      large scale freshwater emergent wetland.
AB  - Transformations and long-term fate of engineered nanomaterials must be measured
      in realistic complex natural systems to accurately assess the risks that they may
      pose. Here, we determine the long-term behavior of poly(vinylpyrrolidone)-coated
      silver nanoparticles (AgNPs) in freshwater mesocosms simulating an emergent
      wetland environment. AgNPs were either applied to the water column or to the
      terrestrial soils. The distribution of silver among water, solids, and biota, and
      Ag speciation in soils and sediment was determined 18 months after dosing. Most
      (70 wt %) of the added Ag resided in the soils and sediments, and largely
      remained in the compartment in which they were dosed. However, some movement
      between soil and sediment was observed. Movement of AgNPs from terrestrial soils
      to sediments was more facile than from sediments to soils, suggesting that
      erosion and runoff is a potential pathway for AgNPs to enter waterways. The AgNPs
      in terrestrial soils were transformed to Ag(2)S (~52%), whereas AgNPs in the
      subaquatic sediment were present as Ag(2)S (55%) and Ag-sulfhydryl compounds
      (27%). Despite significant sulfidation of the AgNPs, a fraction of the added Ag
      resided in the terrestrial plant biomass (~3 wt % for the terrestrially dosed
      mesocosm), and relatively high body burdens of Ag (0.5-3.3 MUg Ag/g wet weight)
      were found in mosquito fish and chironomids in both mesocosms. Thus, Ag from the
      NPs remained bioavailable even after partial sulfidation and when water column
      total Ag concentrations are low (<0.002 mg/L).

PMID- 22463851
TI  - Placenta accreta: depth of invasion and neonatal outcomes.
AB  - OBJECTIVE: The purpose of this study was to compare the risk of adverse neonatal
      outcomes between women with placenta accreta and placenta increta or percreta.
      METHODS: This was a single institution retrospective cohort study of women with
      abnormal placentation (placenta accreta, increta, and percreta) who delivered
      from 1982-2002. Cases were divided into superficial invasion (placenta accreta)
      and deep invasion (placenta increta or percreta), and compared. The primary
      outcomes studied were gestational age at delivery, birth weight, and size for
      gestational age. RESULTS: 103 viable pregnancies with abnormal placentation were
      observed (1.6/1000 pregnancies). Cases of deep invasion had higher parity and
      were more likely to have had a prior cesarean delivery. The mean gestational age
      at delivery was 33 5/7 weeks with deep placental invasion and 35 2/7 weeks in the
      superficial invasion group (p = 0.18). Rates of preterm birth were 64.7% and
      52.3% (p = 0.43) and low birthweight were 24% and 29% (p = 0.76) in the deep and
      superficial invasion groups respectively. There were no differences in the
      remaining outcomes. CONCLUSIONS: Neonatal outcomes of pregnancies complicated by
      placenta increta and percreta are not different than those with placenta accreta.

PMID- 22463852
TI  - [Optic disc drusen and angioid streaks in pseudoxanthoma elasticum].

PMID- 22463853
TI  - [Ocular trauma. Blunt ocular trauma].
AB  - Ocular traumas represent a major public health problem with poorly understood
      ramifications at both the individual and community levels. Any of the ocular
      structures can be damaged in the case of closed globe injury. These lesions,
      often multiple, may appear immediately or in a delayed fashion. Classifications
      have been developed recently in order to better inform the patient of the visual
      prognosis. However, significant efforts are still needed, on the one hand, to
      assess and develop new therapies, and on the other hand, to implement effective
      policies to prevent ocular trauma.

PMID- 22463854
TI  - Intravitreal ranibizumab injection for choroidal neovascularization in Strumpell
      Lorrain Syndrome.
AB  - Strumpell-Lorrain syndrome, or hereditary spastic paraplegia is a genetic disease
      of the central nervous system affecting the spinal cord and cerebellum. It
      represents a clinically heterogenous group of neurodegenerative disorders
      characterized by progressive spasticity and hyperreflexia of the lower limbs.
      Ocular abnormalities include keratitis, macular pigmentary abnormalities,
      juxtafoveolar retinal telangiectasis and choroidal neovascularization. We report
      the first case of choroidal neovascularization associated with Strupell-Lorrain
      syndrome treated successfully with intravitreal ranibizumab injection.

PMID- 22463855
TI  - [Congenital grouped pigmentation of the retina: optical coherence tomographic
      (OCT) analysis].

PMID- 22463856
TI  - [Bilateral sequential central retinal vein occlusion associated with primary
      antiphospholipid syndrome].
AB  - PURPOSE: Case report of a young female patient presenting with bilateral
      sequential central retinal vein occlusion associated with primary
      antiphospholipid syndrome (APS), which rapidly improved with systemic
      anticoagulation. CASE REPORT: A complete ophthalmologic examination and
      hematological evaluation were performed on an 18-year-old female patient
      presenting with unilateral decreased visual acuity in the left eye, secondary to
      a central retinal vein occlusion. Three years later, she experienced a central
      retinal vein occlusion of the right eye. Hematologic evaluation revealed primary
      antiphospholipid syndrome. The patient was treated with systemic anticoagulation.
      RESULTS: One month after the diagnosis and treatment of the central retinal vein
      occlusion in the left eye, the patient discontinued anticoagulant therapy,
      unfortunately resulting in severe visual loss. Three years later, upon recurrence
      in the fellow eye, systemic anticoagulation was reinstituted. Over 12 months
      follow-up, upon complete ophthalmologic examination, the patient showed
      normalization of all retinal signs. CONCLUSION: In the case of young patients
      with bilateral central retinal vein occlusions, hematologic evaluation should be
      performed so as to detect APS. Prompt, effective treatment is necessary to
      prevent further retinal damage. Recurrent thrombotic events may jeopardize
      anatomic and functional prognosis.

PMID- 22463857
TI  - [Axenfeld-Rieger syndrome].

PMID- 22463858
TI  - [Which lenses to use for examination of the vitreous and how to use them
      properly].
AB  - The vitreous is examined with the slit lamp, either alone for observation of the
      anterior third of the vitreous body or by placement of a lens between the slit
      lamp and the patient's eye for observation of the rest. Several types of lens are
      available, both convex and concave, with or without contact, allowing for
      observation of the different parts of the vitreous and retina. Rules concerning
      positioning of the slit lamp, the lens, and the patient must be followed to
      obtain the maximum amount of information.

PMID- 22463859
TI  - Photooxidation of benzene-structured compounds: influence of substituent type on
      degradation kinetic and sum water parameters.
AB  - The combined influence of substituent type and UV/H(2)O(2) process parameters on
      the degradation of four aromatic water pollutants was investigated using modified
      3(3) full factorial design and response surface methodology. Degradation kinetics
      was described by the quadratic polynomial model. According to the applied ANOVA,
      besides pH and [H(2)O(2)], model terms related with the pollutant structure are
      found to be significant. Different optimal operating conditions and values of
      observed degradation rate constants were determined for each of the pollutants
      indicating that the type of substituent influences the overall process
      effectiveness over structurally defined degradation pathway. Biodegradability
      (BOD(5)/COD) and toxicity (TU) were evaluated prior to the treatment and at the
      reference time intervals t(1/2)(P), t(3/4)(P), t(1/4)(OC) and t(1/2)(OC)
      corresponding to the real time required to reduce the concentration of parent
      pollutant and organic content for 1/2, 3/4, 1/4 and 1/2 of initial amount. The
      observed differences are correlated to the structural differences of studied
      aromatics.

PMID- 22463860
TI  - Performance of grass swales for improving water quality from highway runoff.
AB  - The performance of grass swales for treating highway runoff was evaluated using
      an experimental design that allowed for influent and effluent flow and pollutant
      concentration measurements to be taken at specific intervals through each storm
      event. Two common swale design alternatives, pre-treatment grass filter strips
      and vegetated check dams, were compared during 45 storm events over 4.5 years.
      All swale alternatives significantly removed total suspended solids and all
      metals evaluated: lead, copper, zinc, and cadmium. The probability of
      instantaneous concentrations exceeding 30 mg/L TSS was decreased from 41-56% in
      the untreated runoff to 1-19% via swale treatment. Nutrient treatment was
      variable, with generally positive removal except for seasonal events with large
      pulses of release from the swales. Nitrite was the only consistently removed
      nutrient constituent. Chloride concentrations were higher in swale discharges in
      nearly every measurement, suggesting accumulation during the winter and release
      throughout the year. Sedimentation and filtration within the grass layer are the
      primary mechanisms of pollutant treatment; correspondingly, particles and
      particulate-bound pollutants show the greatest removal via swales. Inclusion of
      filter strips or check dams had minimal effects on water quality.

PMID- 22463861
TI  - Improving on SUVA 254 using fluorescence-PARAFAC analysis and asymmetric flow
      field flow fractionation for assessing disinfection byproduct formation and
      control.
AB  - Several challenges with disinfection byproduct (DBP) control stem from the
      complexity and diversity of dissolved organic matter (DOM), which is ubiquitous
      in natural waters and reacts with disinfectants to form DBPs. Fluorescence
      parallel factor (PARAFAC) analysis and asymmetric flow-field flow fractionation
      (AF4) were used in combination with free chlorine DBP formation potential (DBPFP)
      tests to study the physicochemical DOM properties and DBP formation in raw- and
      alum-coagulated waters. Enhanced coagulation with alum became more effective at
      removing DBP-precursors as the pH decreased from 8 to 6. AF4-UV(254) fractograms
      indicated enhanced coagulation at pH 6 preferentially removed larger DOM, whereas
      no preferential size removal occurred at pH 8. Fluorescence-PARAFAC analysis
      revealed the presence of one protein-like and three humic-like fluorophore
      groups; stronger linear correlations were found between chloroform and the
      maximum intensity (F(MAX)) of a humic-like fluorophore (r(2) = 0.84) than with
      SUVA(254) (r(2) = 0.51). This result indicated that the fluorescence-PARAFAC
      approach used here was an improvement on SUVA(254), i.e., fluorescence-based
      measurements were stronger predictors of chloroform formation.

PMID- 22463862
TI  - Persistence of host-associated Bacteroidales gene markers and their quantitative
      detection in an urban and agricultural mixed prairie watershed.
AB  - Microbial source tracking is an emerging tool developed to protect water sources
      from faecal pollution. In this study, we evaluated the suitability of real time
      quantitative PCR (qPCR) Taqman assays developed for detection of host-associated
      Bacteroidales markers in a prairie watershed. The qPCR primers and probes used in
      this study exhibited high accuracy (88-96% sensitivity and >= 99% host
      specificity) in detecting Bacteroidales spp. that are associated with faeces from
      humans, ruminants, bovines, and horses. The ruminant- and human-associated
      markers were also found in high concentrations within individual faecal samples,
      ranging from 3.4 to 7.3 log(10) marker copy numberg(-1) of individual host
      faeces. Following validation of host sensitivity and specificity, the host
      associated Bacteroidales markers were detected in the Qu'Appelle Valley watershed
      of Saskatchewan, Canada which experiences a diversity of anthropogenic inputs.
      Concentrations of the ruminant marker were well-correlated with proximity to
      cattle operations and there was a correlation between the marker and Escherichia
      coli concentrations at these sites. Low concentrations of the human faecal marker
      were measured throughout the sampling sites, and may indicate a consistent influx
      of human faecal pollution into the watershed area. Persistence of each of the
      Bacteroidales host-associated marker was also studied in situ. The results
      indicated that the markers persist for shorter periods of time (99% decay in <8
      days) compared with the conventional E. coli marker (99% decay in >15 days),
      suggesting they are effective at detecting recent faecal contamination events.
      The levels of Bacteroidales markers and E. coli counts did not correlate with the
      presence of the pathogenic bacteria, Salmonella spp. or Campylobacter spp.
      detected in the Qu'Appelle Valley. Collectively, the results obtained in this
      study demonstrated that the qPCR approach for detecting host-associated
      Bacteroidales spp. markers can be a useful tool in helping to determine host
      specific impacts of faecal pollution into a prairie watershed.

PMID- 22463863
TI  - Biotransformation of alkanoylcholines under methanogenic conditions.
AB  - Ester quaternary ammonium compounds (esterquats), which are mainly used as active
      ingredients in fabric softeners and personal care products, are beginning to
      replace traditional quaternary ammonium compounds. As a result of hydrophobicity
      and increasing use, esterquats reach anaerobic treatment systems. However, little
      is known about the fate of esterquats under anaerobic conditions. In the present
      study, the potential inhibitory effect and biotransformation of two
      alkanoylcholines - acetylcholine chloride (ACh-Cl) and lauroylcholine chloride
      (LCh-Cl) - which are simple esterquats, under methanogenic conditions were
      investigated. ACh-Cl up to 300 mg/L was not inhibitory to a mixed methanogenic
      culture. In contrast, methanogenesis was inhibited by LCh-Cl above 50 mg/L,
      primarily caused by the accumulation of lauric acid which resulted from the
      abiotic hydrolysis of LCh. Below inhibitory concentrations, both ACh and LCh were
      transformed to methane by the mixed methanogenic culture. Mass spectrometric
      analysis confirmed that both alkanoylcholines were first abiotically hydrolyzed
      to choline and the corresponding alkanoic acid, which were then biotically
      transformed to methane, carbon dioxide, and ammonia. Thus, alkanoylcholine
      containing waste streams can be bioprocessed to form methane, but hydrolysis
      products such as long-chain alkanoic acids may adversely impact the anaerobic
      bioconversion of alkanoylcholines.

PMID- 22463864
TI  - Characterization of autotrophic and heterotrophic soluble microbial product (SMP)
      fractions from activated sludge.
AB  - Soluble microbial products (SMP) generated by microbial populations can adversely
      affect the efficiency of biological wastewater treatment systems and secondary
      effluent quality. In this work, both experimental and modeling approaches were
      used to investigate the formation of SMP by both heterotrophic and autotrophic
      bacteria. Strategies to control and reduce SMP in activated sludge systems were
      thus evaluated. SMP produced by heterotrophs were found to account for more than
      92% of total SMP. The SMP produced by autotrophs contributed to less than 8% of
      the total SMP, with 5% attributable to the ammonia-oxidizing bacteria (AOB) and
      3% to the nitrite-oxidizing bacteria (NOB). When external organic substrate was
      present, the utilization-associated products (UAP) were the main component of
      SMP. When external organic substrate was completely consumed, biomass-associated
      products (BAP) from the hydrolysis of extracellular polymeric substances (EPS)
      dominated the SMP. The model developed in this study described the fractions and
      dynamics of UAP and BAP produced by heterotrophs, AOB and NOB. Solids retention
      time of the reactor had a significant effect on SMP production, while the effect
      of the hydraulic retention time was only minor. Decreasing the solids retention
      time from 15 to 0.5 d reduced SMP production in the reactor by 62%.

PMID- 22463865
TI  - What makes UK Biobank special?

PMID- 22463866
TI  - Primary tumor of the periacetabular region: resection and reconstruction using a
      segmental ipsilateral femur autograft.
AB  - INTRODUCTION: Bone reconstruction, after periacetabular tumour removal, is a
      complex procedure that carries a high morbidity rate and can result in poor
      clinical outcomes. Among the available options, the Puget pelvic resection
      reconstruction procedure uses an autograft from the ipsilateral proximal femur to
      restore the anatomical and mechanical continuity of the pelvic ring before
      inserting an acetabular implant. HYPOTHESIS AND GOALS: This reconstruction
      technique satisfactorily restores the pelvic anatomy such that functional results
      and morbidity are comparable to alternative reconstruction techniques. PATIENTS
      AND METHODS: This was a retrospective study of 10 patients with an average age of
      38.2 years (range 19 to 75) at the surgical procedure (performed between 1986 and
      2007). There were five chondrosarcomas, three Ewing tumours, one plasmacytoma and
      one giant cell tumour. The position of the hip centre of rotation after
      reconstruction and autograft integration were evaluated on radiographs.
      Functional results were evaluated through the Musculoskeletal Tumor Society
      (MSTS) score and the Postel and Merle d'Aubigne (PMA) score. RESULTS: At the time
      of review, one patient was lost to follow-up and four had died. On radiographs,
      the hip centre of rotation after reconstruction was higher by a median value of
      15 mm (range 5 to 35) and more lateral by a median value of 6mm (range -5 to 15).
      Upon evaluation of radiographs at a median time of 40 months (range 6 to 252
      months), the autograft was completely integrated in five patients and partially
      integrated in three patients (two patients had a local recurrence). There were no
      cases of autograft fracture or non-union at the junctions of the graft. The
      median MSTS score was 25 out of 30 (range 20 to 29), or 83% (range 67 to 97%) at
      the median clinical follow-up of 82 months (range 49 to 264). The median PMA
      score was 13 out of 18 (range 12 to 18). All living patients were walking without
      assistance. Five patients required nine surgical revisions. Seven were attributed
      directly or indirectly to local recurrence; one revision was performed because of
      instability and one because of early acetabular loosening at 9 months.
      CONCLUSION: This challenging procedure provides satisfactory mechanical and
      anatomical results, while restoring hip anatomy and function. The primary cause
      of failure in this series was local recurrence of the tumour, which highlights
      the need to carefully select the indications and optimize the surgical tumour
      resection.

PMID- 22463867
TI  - Research in orthopaedics from China has thrived over the last decade: a
      bibliometric analysis of publication activity.
AB  - INTRODUCTION: Over the past decades, there have been great advances in
      orthopaedics in China. The purpose of this study was to investigate the
      orthopaedic research output in the three Chinese-speaking regions - the Mainland
      (ML), Hong Kong (HK), and Taiwan (TW). HYPOTHESIS: We hypothesized that there was
      a positive trend in China orthopaedic research during the past decade and this
      regardless of the Chinese-speaking regions of origin. MATERIALS AND METHODS:
      Forty-nine orthopaedic journals were retrieved from the PubMed database and
      Science Citation Index Expanded. Articles from ML, TW, and HK in 2000 to 2009
      were identified. The total number of articles, clinical trials, randomized
      controlled trials (RCTs), impact factors (IF), citations, and articles published
      in the top 10 orthopaedic journals were analyzed. RESULTS: A total of 1878
      published articles in 2000 to 2009 were broken down as follows: ML (607), TW
      (865), and HK (406). There was a significant increase in published articles for
      ML and TW from 2000 to 2009. The number of published articles from ML exceeded
      the total sum of articles from TW and HK in 2009. The accumulated IF of articles
      from TW (1751.91) was higher than that from ML (1054.67) and HK (708.25). TW had
      the highest average IF (2.025), followed by ML (1.902) and HK (1.862). The total
      citations of published articles in 2000 to 2009 from TW (4759) were higher than
      those for HK (2276) and ML (1751). The highest average citation of each article
      was from HK (5.784), followed by TW (5.720) and ML (3.051). TW published 339
      articles in 10 high-impact journals, whereas ML and HK published 267 and 154
      articles, respectively. DISCUSSION: Chinese researchers in the field of
      orthopaedics have been more and more active in the global orthopaedic community
      during the past 10 years. ML seems to have caught up to HK and TW in respect to
      research output.

PMID- 22463868
TI  - Dual mobility cups hip arthroplasty as a treatment for displaced fracture of the
      femoral neck in the elderly. A prospective, systematic, multicenter study with
      specific focus on postoperative dislocation.
AB  - INTRODUCTION: Displaced fractures of the femoral neck in the elderly are best
      treated with arthroplasty. The type of arthroplasty to be used, either hemi- or
      total hip arthroplasty, remains controversial as total hip replacements
      potentially have a higher rate of dislocation. HYPOTHESIS: Dual mobility cups
      have a low dislocation rate when used to manage acute fractures of the femoral
      neck. PATIENTS AND METHODS: In a multicenter prospective study conducted in
      France over an inclusion time of 3 months, all displaced fractures of the femoral
      neck treated with arthroplasty were operated on with insertion of a dual mobility
      cup. Patients had clinical and radiological assessment at 3, 6, and 9 months
      postoperative. RESULTS: Two hundred and fourteen hips in 214 patients with a mean
      age of 83 years (range, 70-103 years) were included. None of the patients was
      lost to follow-up. The mortality rate after 9 months was 19%. Two patients (1%)
      had early postoperative infection successfully treated with lavage and
      antibiotics. Three patients (1.4%), operated through a posterior approach,
      presented one postoperative dislocation, all of which were posterior. Reduction
      was performed through closed external manipulation under general anesthesia.
      There was no recurrence of dislocation. DISCUSSION: This low rate of dislocation
      after acute total hip replacement using dual mobility design cups favorably
      compares with hemiarthroplasties. Dual mobility cups might therefore be
      considered a valuable option to prevent postoperative dislocation when treating
      displaced intracapsular fractures of the proximal femur in elderly patients if a
      total hip replacement is recommended. Further study is needed before extending
      the indications for total hip arthroplasty following a fracture of the femoral
      neck, to assess the potential cost and complications of a longer procedure with
      its potential acetabular complication, and weigh them against the potential
      benefits.

PMID- 22463869
TI  - Enterobacteriaceae producing the KPC-2 carbapenemase from hospital sewage.
AB  - Fifteen isolates with reduced susceptibility to meropenem were obtained from
      hospital sewage. They contained bla(KPC-2) and belonged to multiple clones of
      Citrobacter freundii or Enterobacter cloacae. bla(KPC-2) was commonly carried by
      self-transmissible plasmids with different EcoRI-restricted patterns. Tn2 was
      identified upstream of bla(KPC-2), while ISKpn6 lay downstream. Hospital sewage
      could be an important reservoir of bla(KPC-2) and warrants more studies.

PMID- 22463870
TI  - Prediction of community-onset bacteremia among febrile adults visiting an
      emergency department: rigor matters.
AB  - OBJECTIVES: Bacteremia is a severe bacterial infection with significant mortality
      and morbidity. Clinical parameters that reliably predict the presence of
      community-onset bacteremia are less elucidated. METHODS: During 96 randomly
      selected days between August 2006 and July 2007, a prospective study was
      conducted to analyze the risk factors of community-onset bacteremia among febrile
      adults who visited the emergency department (ED) of a medical center. Patients
      hospitalized in the 30 days prior to the study, patients experiencing
      consciousness alteration, and nursing facility residents were excluded. RESULTS:
      The mean age of the 396 febrile adults enrolled in the study was 53.8 years
      (range, 18-95 years), and 60 (15.2%) patients had true bacteremia, with the
      predominance of monomicrobial Gram-negative pathogens (42 patients). In a
      multivariate analysis, several factors were independently associated with
      community-onset bacteremia, including an age of >65 years (odds ratio [OR], 2.81;
      95% confidence interval [CI], 1.25-6.33), the presence of rigor (OR, 13.7; 95%
      CI, 4.47-42.0) or chills (OR, 6.04; 95% CI, 1.10-32.9), a body temperature >39.9 
      degrees C (OR, 2.68; 95% CI, 1.03-6.94), blood urea nitrogen >20 mg/dL (OR, 5.56;
      95% CI, 2.03-15.7), a blood urea nitrogen/creatinine ratio >16 (OR, 2.29; 95% CI,
      1.03-5.11), and thrombocytopenia (OR, 6.09; 95% CI, 1.84-20.0). After scoring
      each risk factor, a logistic regression model for the prediction of bacteremia
      was developed, and the area under the receiver operating characteristic curve was
      0.91. CONCLUSIONS: Some easily determined clinical parameters were independently
      associated with community-onset bacteremia among febrile adults, and the most
      significant predictor was the presence of rigor. Although the proposed predictive
      model needs further validation, it may be of use for the early identification of
      bacteremic episodes in ED practice.

PMID- 22463871
TI  - The Nordic Nutrition Recommendations and prostate cancer risk in the Cancer of
      the Prostate in Sweden (CAPS) study.
AB  - OBJECTIVE: The Nordic Nutrition Recommendations (NNR) aim at preventing diet
      associated diseases such as cancer in the Nordic countries. We evaluated
      adherence to the NNR in relation to prostate cancer (PC) in Swedish men,
      including potential interaction with a genetic risk score and with lifestyle
      factors. DESIGN: Population-based case-control study (Cancer of the Prostate in
      Sweden (CAPS), 2001-2002). Using data from a semi-quantitative FFQ, we created an
      NNR adherence score and estimated relative risks of PC by unconditional logistic
      regression. Individual score components were modelled separately and potential
      modifying effects were assessed on the multiplicative scale. SETTING: Four
      regions in the central and northern parts of Sweden. SUBJECTS: Incident PC
      patients (n 1386) and population controls (n 940), frequency-matched on age and
      region. RESULTS: No overall association with PC was found, possibly due to the
      generally high adherence to the NNR score and its narrow distribution in the
      study population. Among individual NNR score components, high compared with low
      intakes of polyunsaturated fat were associated with an increased relative risk of
      localized PC. No formal interaction with genetic or lifestyle factors was
      observed, although in stratified analysis a positive association between the NNR
      and PC was suggested among men with a high genetic risk score but not among men
      with a medium or low genetic risk score. CONCLUSIONS: Our findings do not support
      an association between NNR adherence and PC. The suggestive interaction with the
      genetic risk score deserves further investigations in other study populations.

PMID- 22463872
TI  - Training the brain: fact and fad in cognitive and behavioral remediation.
AB  - Putatively safe and effective for improving cognitive performance in both health
      and disease, products purported to train the brain appeal to consumers and
      healthcare practitioners. In an increasingly health-centered society, these
      applications constitute a burgeoning commercial market. Sparse evidence coupled
      with lack of scientific rigor, however, leaves claims concerning the impact and
      duration of such brain training largely unsubstantiated. On the other hand, at
      least some scientific findings seem to support the effectiveness and
      sustainability of training for higher brain functions such as attention and
      working memory. In the present paper we provide a tectonic integration and
      synthesis of cognitive training approaches. Specifically, we sketch the relative
      merits and shortcomings of these programs, which often appeal to parents who must
      choose between side-effect-laden medication and other less conventional options.
      Here we examine how neuroplasticity allows the healthy as well the impaired to
      benefit from cognitive training programs. We evaluate the evidence and consider
      whether brain training can be a stand-alone treatment or an adjunct to
      pharmacotherapy, outline promising future prospects, and highlight what training
      outcomes are plausible in line with available data. Future research would
      determine whether the field of brain training realizes its potential to
      revolutionize education and rehabilitation or withers away engulfed in
      controversy.

PMID- 22463873
TI  - Tailored strategies for radiation therapy in classical Hodgkin's lymphoma.
AB  - Radiotherapeutic advances have contributed to the evolution of Hodgkin's lymphoma
      (HL) treatment paradigms. A reduction in radiation therapy (RT) field size and
      dose has the potential to significantly impact the therapeutic ratio by
      diminishing late toxicities while maintaining curability. Substantial progress in
      risk stratification has contributed to the development of tailored RT strategies
      which address both field design as well as dose. Technologic improvements have
      also enhanced the ability to adapt the RT technique to the individual patient.
      The refinement of the RT approach and its incorporation into current combined
      modality strategies in adult classical HL is the subject of ongoing investigation
      and is critically reviewed.

PMID- 22463874
TI  - Prognostic value of RKIP and p-ERK in gastric cancer.
AB  - BACKGROUND: The mitogen-activated protein kinase (MAPK) signaling pathway
      participates in several steps of tumour development and is considered a prominent
      therapeutic target for the design of chemotherapeutic agents. We evaluated the
      expressions of extracellular signal-regulated kinase (ERK), mitogen-activated
      protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor
      protein (RKIP), and investigated correlations of these expressions with
      clinicopathological features and outcomes in gastric cancer. METHODS: Tumour
      samples were obtained from 105 patients with gastric adenocarcinomas who
      underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK),
      phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical
      staining. RESULTS: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54
      (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively
      correlated with the depth of invasion (p < 0.001), lymph node involvement (p =
      0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP
      expression was associated with significantly longer relapse-free survival (RFS)
      (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression
      had slightly, but not significantly shorter RFS than those without such
      expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression
      had significantly shorter RFS than the other patients (p < 0.001). The
      combination of RKIP and p-ERK expression was an independent prognostic factor
      (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008). CONCLUSIONS:
      Our results demonstrated that loss of RKIP was associated with tumour progression
      and poor survival. Negative RKIP expression combined with positive p-ERK
      expression was an independent predictor of poor outcomes in patients with gastric
      cancer.

PMID- 22463875
TI  - Bronchoscopic management of a rare benign endobronchial tumor.
AB  - Benign endobronchial tumors are uncommon. Bronchoscopic removal is the preferred
      modality of treatment although surgery may be required in some cases. Rigid
      bronchoscopy is usually recommended in the management of these tumors. However,
      flexible bronchoscopy is also used in many centers. We present a case of
      endobronchial lipoma, where an unusual complication during flexible bronchoscopic
      resection using snare forceps necessitated urgent rigid bronchoscopy. This case
      highlights the importance of rigid bronchoscopy in the management of
      endobronchial tumors. We believe that with a large benign endobronchial tumor in
      tracheal or main-stem bronchus, physicians should initially employ rigid
      bronchoscopy, switching to flexible if more peripheral treatment is required.

PMID- 22463876
TI  - Anthelmintic effects of citrus peels ethanolic extracts against Ascaridia galli.
AB  - The use of phytogenic bioactive compounds to control poultry helminthes is
      increasing in different production systems. In vitro and in vivo anthelmintic
      activity of citrus peels against Ascaridia galli was investigated. Ethanolic
      extracts of three citrus peels species were suspended in 0.5% dimethyl sulfoxide
      (DMSO) to form an experimental composition (EC). EC was mainly composed of
      Limonene (96%), followed by beta-Pinene (1.5%), alpha-Pinene (0.5%), and Sabinene
      (0.3%). For in vitro investigation, adult A. galli worms (n=225) were collected
      from naturally infected chickens and distributed to 3 equal groups. Groups 1, 2,
      and 3 were exposed to Fenbendazole (0.5mg/ml), EC (50mg/ml), and 0.5% DMSO,
      respectively. For in vivo investigation, 200 Lohmann Selected Leghorns chicks
      were infected at 1-day old with 250 embryonated A. galli eggs. At 6 weeks of age,
      150 A. galli infected birds were randomly allocated into 5 equal groups. Groups
      1, 2, and 3 were treated with 300, 600, and 1200 mg EC kg(-1) body weight,
      respectively. Group 4 was treated with Fenbendazole (50 mg kg(-1)). Group 5 was
      left as control. Birds were euthanized 2-weeks post-treatment, and all worms were
      collected from their intestines. EC possessed significant (P<0.001) in vitro
      anthelmintic properties on live worms. No significant (P>0.05) difference was
      quantified between number of motile worms exposed either to EC or Fenbendazole 7h
      post-exposure. A significant (P<0.0001) reduction in fecal egg count was observed
      14 days post-treatment with 1200 mg kg(-1) EC. No significant differences were
      observed in worm burden of the 300 mg EC-treated group compared to the controls.
      In contrast, the 600 and 1200 mg EC-treated groups showed significant (P<0.0001)
      reduction in worm burden. Fenbendazole was the most effective in reducing A.
      galli burden (Efficacy=97%) followed by 1200 mg EC kg(-1) (68%), 600 mg EC kg(-1)
      (66%), and 300 mg EC kg(-1) (5%). It is concluded that citrus peels extracts have
      potential anthelmintic properties against A. galli.

PMID- 22463877
TI  - On sharing quantitative trait GWAS results in an era of multiple-omics data and
      the limits of genomic privacy.
AB  - Recent advances in genome-scale, system-level measurements of quantitative
      phenotypes (transcriptome, metabolome, and proteome) promise to yield
      unprecedented biological insights. In this environment, broad dissemination of
      results from genome-wide association studies (GWASs) or deep-sequencing efforts
      is highly desirable. However, summary results from case-control studies (allele
      frequencies) have been withdrawn from public access because it has been shown
      that they can be used for inferring participation in a study if the individual's
      genotype is available. A natural question that follows is how much private
      information is contained in summary results from quantitative trait GWAS such as
      regression coefficients or p values. We show that regression coefficients for
      many SNPs can reveal the person's participation and for participants his or her
      phenotype with high accuracy. Our power calculations show that regression
      coefficients contain as much information on individuals as allele frequencies do,
      if the person's phenotype is rather extreme or if multiple phenotypes are
      available as has been increasingly facilitated by the use of multiple-omics data
      sets. These findings emphasize the need to devise a mechanism that allows data
      sharing that will facilitate scientific progress without sacrificing privacy
      protection.

PMID- 22463878
TI  - Ultrafiltration rate as a nursing-sensitive quality indicator in haemodialysis.
AB  - Nursing quality indicators are widely used to demonstrate nurses' contributions
      to health care. Some studies in nephrology settings have addressed nursing
      quality, but indicators reflecting the nursing process quality in haemodialysis
      are lacking. This paper argues for considering ultrafiltration rate as a nursing
      sensitive quality indicator in haemodialysis. Strategies and qualifications for
      considering ultrafiltration rate as a nursing quality indicator are established
      and discussed. It is argued that the indicator is associated with nursing
      practice, linked to both morbidity and mortality, and is within the scope of the
      nurse's responsibility. It is also argued that the indicator could be influenced
      by other factors than nursing care. Thus, further studies are needed to
      investigate the association between ultrafiltration rate and patient safety. The
      introduction of the ultrafiltration rate as a duty specific quality indicator is
      a coveted measure of nursing care quality in haemodialysis settings.

PMID- 22463885
TI  - Prosthetic H-graft portacaval shunts vs transjugular intrahepatic portasystemic
      stent shunts: 18-year follow-up of a randomized trial.
AB  - BACKGROUND: Widespread application of transjugular intrahepatic portasystemic
      shunt (TIPS) continues despite the lack of trials documenting efficacy superior
      to surgical shunting. Here we present an 18-year follow-up of a prospective
      randomized trial comparing TIPS with small-diameter prosthetic H-graft portacaval
      shunt (HGPCS) for portal decompression. STUDY DESIGN: Beginning in 1993, patients
      were prospectively randomized to undergo either TIPS or HGPCS as definitive
      therapy for portal hypertension due to cirrhosis. Complications of shunting and
      long-term outcomes were noted. Failure of shunting was prospectively defined as
      the inability to place shunt, irreversible shunt occlusion, major variceal
      rehemorrhage, unanticipated liver transplantation, or death. Survival and shunt
      failure were compared using Kaplan-Meier curve analysis. Median data are
      reported. RESULTS: Patient presentation, circumstances of shunting, causes of
      cirrhosis, severity of hepatic dysfunction (eg, Child's class, Model for End
      Stage Liver Disease score), and predicted survival after shunting did not differ
      between patients undergoing TIPS (n = 66) or HGPCS (n = 66). Survival was
      significantly longer after HGPCS for patients of Child's class A (91 vs 19
      months; p = 0.009) or class B (63 vs 21 months; p = 0.02). Shunt failure occurred
      later after HGPCS than TIPS (45 vs 22 months; p = 0.04). CONCLUSIONS: Compared
      with TIPS, survival after HGPCS was superior for patients with better liver
      function (eg, Child's class A or B). Shunt failure after HGPCS occurred later
      than after TIPS. Rather than TIPS, application of HGPCS is preferred for patients
      with complicated cirrhosis and better hepatic function.

PMID- 22463880
TI  - Improved long-term survival of dialysis patients after near-total
      parathyroidectomy.
AB  - BACKGROUND: Severe secondary hyperparathyroidism, which is associated with life
      threatening complications, can develop in dialysis-dependent end-stage renal
      disease patients. The aim of this study was to compare short- and long-term
      mortality in dialysis patients who underwent near-total parathyroidectomy (NTPTX)
      and matched nonoperated controls. STUDY DESIGN: We identified 150 dialysis
      patients who underwent NTPTX (1993-2009) at our institution and compared them
      with 1,044 nonoperated control patients identified in the US Renal Data System
      registry, matched for age, sex, race, diabetes as cause of kidney failure, years
      on dialysis, and dialysis modality. Survival outcomes were estimated using
      multivariable Cox proportional hazards models with stratification on the matching
      sets, adjusted for cardiovascular comorbidities, smoking, inability to
      ambulate/transfer, and payor status. RESULTS: During a follow-up of a mean of 3.6
      years (range 0.1 month to 16.4 years), NTPTX patients had a significant reduction
      in the long-term risk of all-cause death (hazard ratio = 0.68; 95% CI, 0.52-0.89;
      p = 0.006) compared with controls. Thirty-day mortality rates for NTPTX patients
      and controls were 246 vs 105 per 1,000 person-years (p = 0.21). In adjusted
      analyses, NTPTX patients had a 37% reduced risk of all-cause death and a 33%
      reduced risk of cardiovascular death compared with controls. A durable reduction
      in mean parathyroid hormone was observed after NTPTX; from 1,776 +/- 1,416.6
      pg/mL to 301 +/- 285.7 pg/mL (p < 0.0001). CONCLUSIONS: In our center, NTPTX in
      dialysis patients was associated with a significant reduction in long-term risk
      of death compared with matched control patients, without a significantly
      increased short-term risk.

PMID- 22463910
TI  - Surgical management of late sequelae in survivors of an episode of acute
      necrotizing pancreatitis.
AB  - BACKGROUND: After surviving an episode of acute necrotizing pancreatitis (ANP), a
      variety of late sequelae develop and require nonoperative or operative
      interventions. Persistent pancreatic fistula, fluid collections, recurrent
      pancreatitis, sepsis, pain, and intolerance of po intake are seen. STUDY DESIGN:
      We have maintained records for all patients hospitalized from 1993 through 2010
      with a diagnosis of ANP. Once discharged from hospital, patients were managed
      with routine clinic follow-up at close intervals and later at 6-month intervals.
      Using ERCP or magnetic resonance cholangiopancreatography, all patients'
      pancreatic ducts were classified as type I (normal), type II (stricture), or type
      III (disconnected). Patients were monitored for the complications mentioned.
      Operations performed >8 weeks after the initial episode of ANP were defined as
      late and evaluated for operative mortality, morbidity, success in resolving
      symptoms/collections, and length of stay. RESULTS: One hundred and ninety-seven
      patients with ANP were included. Seventy-one late operations were performed (59
      drainage procedures/12 resections). Operative mortality was 1%, morbidity was
      19%, and mean length of stay was 6.3 +/- 5.6 days. Poor po intake was seen in 80%
      of operated patients and total parenteral nutrition dependence in 42%. Duct type
      correlated with pancreatic debridement, persistent fluid collection/fistula,
      pain, po intake intolerance, and late operation. Late operation successfully
      resolved symptoms and/or fluid collections in 96%. Recurrent pancreatitis was
      improved in 87% and eliminated in 78%. CONCLUSIONS: Patients who require late
      operation after surviving an episode of ANP are more likely to have sustained
      ductal injuries and are likely to require operation for either pain or for
      inability to tolerate po intake. Operation can be performed safely with a low
      mortality.

PMID- 22463890
TI  - Five-year outcomes after oxandrolone administration in severely burned children:
      a randomized clinical trial of safety and efficacy.
AB  - BACKGROUND: Oxandrolone, an anabolic agent, has been administered for 1 year post
      burn with beneficial effects in pediatric patients. However, the long-lasting
      effects of this treatment have not been studied. This single-center prospective
      trial determined the long-term effects of 1 year of oxandrolone administration in
      severely burned children; assessments were continued for up to 4 years post
      therapy. STUDY DESIGN: Patients 0 to 18 years old with burns covering >30% of the
      total body surface area were randomized to receive placebo (n = 152) or
      oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge,
      patients were randomized to a 12-week exercise program or to standard of care.
      Resting energy expenditure, standing height, weight, lean body mass, muscle
      strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual
      maturation, and concentrations of serum inflammatory cytokines, hormones, and
      liver enzymes were monitored. RESULTS: Oxandrolone substantially decreased
      resting energy expenditure and rate pressure product, increased insulin-like
      growth factor-1 secretion during the first year after burn injury, and, in
      combination with exercise, increased lean body mass and muscle strength
      considerably. Oxandrolone-treated children exhibited improved height percentile
      and BMC content compared with controls. The maximal effect of oxandrolone was
      found in children aged 7 to 18 years. No deleterious side effects were attributed
      to long-term administration. CONCLUSIONS: Administration of oxandrolone improves
      long-term recovery of severely burned children in height, BMC, cardiac work, and
      muscle strength; the increase in BMC is likely to occur by means of insulin-like
      growth factor-1. These benefits persist for up to 5 years post burn.

PMID- 22463915
TI  - How does laparoscopic-assisted hepatic resection compare with the conventional
      open surgical approach?
AB  - BACKGROUND: Laparoscopic-assisted hepatic resection (LAHR) has been described as
      a safe and reliable means of liver resection for tumors or live-donor
      hepatectomy. Here we compare the outcomes in paired cohorts between patients
      undergoing open hepatic resection (OHR) and LAHR. STUDY DESIGN: Two hundred and
      twelve patients who underwent either OHR or LAHR from March 2004 to July 2011
      were analyzed to assess outcomes. During this time period, 124 patients underwent
      OHR and 88 underwent LAHR. Demographic and outcomes data were assessed. RESULTS:
      In the total patient cohort, mean age found in both surgical arms was similar, as
      was the mean BMI. In addition, there was no difference in the cohort between
      those who underwent either minor or major hepatic resections (p = 0.52).
      Operatively, in the OHR arm the mean duration of the operation was 234 minutes
      and comparable with LAHR at 238 minutes (p = 0.75). There was also no difference
      in the mean lesion size in the OHR (5.72 cm) and LAHR (5.37 cm) groups (p =
      0.55). Notably, there was no difference in the complication incidence rates,
      which were 10.5% (OHR) and 6.8% (LAHR) (p = 0.59). However, when analyzing for
      length of stay, there was a significant difference between the 2 arms; patients
      in OHR arm had longer stays than those in the LAHR arm (7.59 days vs 6.30 days,
      respectively; mean difference 1.29 days; 95% CI, 0.08-2.5; p = 0.036).
      CONCLUSIONS: Although reduced surgical pain, improved cosmesis, and shortened
      hospital stays have been shown to correlate with laparoscopic abdominal
      procedures, our study indicates these marked advantages are also conferred to
      those undergoing LAHR. In addition, these findings demonstrate the use of LAHR
      and highlight the need for the addition of this technique to the liver surgeon's
      skill set.

PMID- 22463919
TI  - Prevalence of left and balanced coronary arterial dominance decreases with
      increasing age of patients at autopsy. A postmortem coronary angiograms study.
AB  - BACKGROUND: In patients presenting with an acute coronary syndrome, left over
      right coronary dominance appears to be independently associated with increased
      long-term mortality. This could lead to decreasing numbers of patients with a
      left dominant coronary artery system in older age groups. METHODS: We assessed
      the type of coronary dominance in different age groups in postmortem angiograms
      that were routinely performed at autopsy between 1993 and 2007. Coronary
      dominance was determined by identifying the origin of the posterior descending
      artery and posterolateral branches on postmortem angiography. Age, gender, and
      cause of death were recorded from the autopsy database. The prevalence of left
      dominant, right dominant, and codominant systems was determined in three
      increasing age categories, with cutoffs based on tertiles. RESULTS: A total 1620
      coronary angiograms were assessed; 167 were excluded because it was not possible
      to determine coronary dominance. The median age of all patients was 71 years; 56%
      were male. Of all deaths, 40% were classified as cardiac. Regarding coronary
      dominance, 81.2% was right, 9.1% was left, and 9.7% was codominant. Overall, a
      decrease in prevalence of left and codominant coronary systems was observed with
      increasing age in the three age cohorts (<= 63 years, 64-75 years, and >= 76
      years) (P=.001 for overall comparison). CONCLUSIONS: In this large autopsy
      cohort, the prevalence of a left dominant or codominant coronary system decreased
      with increasing age. These findings could relate to a slightly higher risk of
      mortality in case of left versus right coronary artery occlusion.

PMID- 22463920
TI  - Healthcare-associated infection in hematopoietic stem cell transplantation
      patients: risk factors and impact on outcome.
AB  - OBJECTIVE: The objective of this study was to analyze the incidence of and risk
      factors for healthcare-associated infections (HAI) among hematopoietic stem cell
      transplantation (HSCT) patients, and the impact of such infections on mortality
      during hospitalization. METHODS: We conducted a 9-year (2001-2009) retrospective
      cohort study including patients submitted to HSCT at a reference center in Sao
      Paulo, Brazil. The incidence of HAI was calculated using days of neutropenia as
      the denominator. Data were analyzed using EpiInfo 3.5.1. RESULTS: Over the 9-year
      period there were 429 neutropenic HSCT patients, with a total of 6816 days of
      neutropenia. Bloodstream infections (BSI) were the most frequent infection,
      presenting in 80 (18.6%) patients, with an incidence of 11.7 per 1000 days of
      neutropenia. Most bacteremia was due to Gram-negative bacteria: 43 (53.8%) cases
      were caused by Gram-negative species, while 33 (41.2%) were caused by Gram
      positive species, and four (5%) by fungal species. Independent risk factors
      associated with HAI were prolonged neutropenia (odds ratio (OR) 1.07, 95%
      confidence interval (CI) 1.04-1.10) and duration of fever (OR 1.20, 95% CI 1.12
      1.30). Risk factors associated with death in multivariate analyses were age (OR
      1.02, 95% CI 1.01-1.43), being submitted to an allogeneic transplant (OR 3.08,
      95% CI 1.68-5.56), a microbiologically documented infection (OR 2.96, 95% CI 1.87
      4.6), invasive aspergillosis disease (OR 2.21, 95% CI 1.1-4.3), and acute
      leukemias (OR 2.24, 95% CI 1.3-3.6). CONCLUSIONS: BSI was the most frequent HAI,
      and there was a predominance of Gram-negative microorganisms. Independent risk
      factors associated with HAI were duration of neutropenia and fever, and the risk
      factors for a poor outcome were older age, type of transplant (allogeneic), the
      presence of a microbiologically documented infection, invasive aspergillosis, and
      acute leukemia. Further prospective studies with larger numbers of patients may
      confirm the role of these risk factors for a poor clinical outcome and death in
      this transplant population.

PMID- 22463921
TI  - High-SPF sunscreens (SPF >= 70) may provide ultraviolet protection above minimal
      recommended levels by adequately compensating for lower sunscreen user
      application amounts.
AB  - BACKGROUND: The manner in which consumers apply sunscreens is often inadequate
      for ultraviolet protection according to the labeled sun protection factor (SPF).
      Although sunscreen SPFs are labeled by testing at an application density of 2
      mg/cm(2), the actual protection received is often substantially less because of
      consumer application densities ranging from 0.5 to 1 mg/cm(2). High-SPF
      sunscreens may provide more adequate protection even when applied by consumers at
      inadequate amounts. OBJECTIVE: We sought to measure the actual SPF values of
      various sunscreens (labeled SPF 30-100) applied in amounts typical of those used
      by consumers. METHODS: Actual SPF values were measured on human volunteers for 6
      sunscreen products with labeled SPF values ranging from 30 to 100, applied at
      0.5, 1.0, 1.5, and 2.0 mg/cm(2). RESULTS: There was a linear relationship between
      application density and the actual SPF; sunscreens with labeled SPF values of 70
      and above provided significant protection, even at the low application densities
      typically applied by consumers. Sunscreens labeled SPF 70 and 100 applied at 0.5
      mg/cm(2) provided an actual SPF value of, respectively, 19 and 27. LIMITATIONS:
      The study was conducted in a laboratory setting under standardized conditions and
      results are extrapolated to actual in-use situations. CONCLUSION: Sunscreens with
      SPF 70 and above add additional clinical benefits when applied by consumers at
      typically used amounts, by delivering an actual SPF that meets the minimum SPF
      levels recommended for skin cancer and photodamage prevention. In contrast,
      sunscreens with SPF 30 or 50 may not produce sufficient protection at actual
      consumer usage levels.

PMID- 22463922
TI  - Safety and efficacy of a monoclonal antibody to proprotein convertase
      subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with
      primary hypercholesterolemia receiving ongoing stable atorvastatin therapy.
AB  - OBJECTIVES: The primary objective of this study was to evaluate the low-density
      lipoprotein cholesterol (LDL-C)-lowering efficacy of 5 SAR236553/REGN727
      (SAR236553) dosing regimens versus placebo at week 12 in patients with LDL-C
      >=100 mg/dl on stable atorvastatin therapy. Secondary objectives included
      evaluation of effects on other lipid parameters and the attainment of LDL-C
      treatment goals of <100 mg/dl (2.59 mmol/l) and <70 mg/dl (1.81 mmol/l).
      BACKGROUND: Serum proprotein convertase subtilisin kexin 9 (PCSK9) binds to low
      density lipoprotein receptors, increasing serum LDL-C. SAR236553 is a fully human
      monoclonal antibody to PCSK9. METHODS: This double-blind, parallel-group, placebo
      controlled trial randomized 183 patients with LDL-C >=100 mg/dl (2.59 mmol/l) on
      stable-dose atorvastatin 10, 20, or 40 mg for >=6 weeks to: subcutaneous placebo
      every 2 weeks (Q2W); SAR236553 50, 100, or 150 mg Q2W; or SAR236553 200 or 300 mg
      every 4 weeks (Q4W), alternating with placebo for a total treatment period of 12
      weeks. RESULTS: SAR236553 demonstrated a clear dose-response relationship with
      respect to percentage LDL-C lowering for both Q2W and Q4W administration: 40%,
      64%, and 72% with 50, 100, and 150 mg Q2W, respectively, and 43% and 48% with 200
      and 300 mg Q4W. LDL-C reduction with placebo at week 12 was 5%. SAR236553 also
      substantially reduced non-high-density lipoprotein cholesterol, apolipoprotein B,
      and lipoprotein(a). SAR236553 was generally well tolerated. One patient on
      SAR236553 experienced a serious adverse event of leukocytoclastic vasculitis.
      CONCLUSIONS: When added to atorvastatin, PCSK9 inhibition with SAR236553 further
      reduces LDL-C by 40% to 72%. These additional reductions are both dose- and
      dosing frequency-dependent. (Efficacy and Safety Evaluation of SAR236553
      [REGN727] in Patients With Primary Hypercholesterolemia and LDL-cholesterol on
      Stable Atorvastatin Therapy; NCT01288443).

PMID- 22463923
TI  - Strong monovalent electrolyte imbalances in serum of dogs infected with Babesia
      canis.
AB  - Canine babesiosis is a systemic tick-borne protozoan disease caused by infection
      with parasites of the genus Babesia. Acid-base disorders and ion imbalances have
      been described in dogs infected with Babesia rossi in South Africa. In this
      paper, the authors describe changes to monovalent ion concentrations and
      calculated parameters of monovalent ions in 70 dogs naturally infected with B.
      canis, a species occurring in Europe. Hyponatraemia, hypokalaemia,
      hyperchloraemia, decrease of chloride gap, strong ion gap, difference between
      sodium and chloride concentrations, and an increase of chloride-to-sodium and
      sodium-to-potassium ratios were the most prevalent changes. Hyponatraemia,
      hypokalaemia and hyperchloraemia were detected less frequently than in dogs
      infected with B. rossi, but the severity of these changes were similar.
      Comparison of monovalent ion concentrations in azotaemic and non-azotaemic, and
      anaemic and non-anaemic dogs infected with B. canis showed that azotaemic dogs
      had significantly lower sodium concentrations. The results of this study indicate
      a possible development of hyperchloraemic acidosis and the probable contribution
      of aldosterone in the development of hypokalaemia. However, further study on
      blood gas, aldosterone, and antidiuretic hormone in dogs infected with B. canis
      is needed.

PMID- 22463924
TI  - Dynamic splinting with early motion following zone IV/V and TI to TIII extensor
      tendon repairs.
AB  - PURPOSE: To investigate the influence of a dynamic splinting protocol on outcomes
      of extensor tendon repairs. METHODS: All patients in a prospectively collected
      database underwent extensor tendon repair by a single surgeon between 2004 and
      2008. The inclusion criterion was simple extensor tendon repairs in zone IV and V
      in the fingers and zones TI to TIII in the thumb. The tendon repairs used a 4
      strand core technique and running epitendinous suture. Within 7 days, each
      subject began using a dynamic extension splint during the day and a static
      extension splint at night. The extension splint allowed the patient to passively
      extend and actively flex the digits. After 3 weeks, the dynamic splint was
      discontinued and the patients were started on active digital motion. Static night
      splinting was continued for the next 3 weeks, after which time splinting was
      discontinued and strengthening was instituted. A total of 17 patients with 19
      tendon lacerations met the inclusion criterion. There were 5 patients with
      lacerations of the thumb extensors and 12 patients with zone IV/V finger extensor
      tendon lacerations. The average time from injury to surgery was 11 days (range, 2
      39 d). The follow-up was 43 to 215 days, with an average of 96 days. RESULTS: A
      total of 16 patients achieved good or excellent results by 6 weeks according to
      our grading system. One patient had a fair result. There were no ruptures and no
      tenolysis surgeries performed. CONCLUSIONS: Dynamic splinting resulted in
      generally good functional outcomes for extensor tendon laceration repairs in zone
      IV/V and TI to TIII, without complications. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 22463925
TI  - Stress fracture of the radius diaphysis in a skeletally immature wrestler.
AB  - Stress fractures in the forearm are rare events. Failure to detect a nondisplaced
      stress fracture could lead to further injury or fracture displacement. We present
      a case of a 15-year-old male wrestler without overt risk factors, who presented
      with a transverse stress fracture in the middle third of the radial diaphysis.
      The clinician should consider this diagnosis when examining athletes with
      otherwise unexplained forearm pain.

PMID- 22463926
TI  - The scaphotrapezial joint after partial trapeziectomy for trapeziometacarpal
      joint arthritis: long-term follow-up.
AB  - PURPOSE: Partial trapeziectomy addresses trapeziometacarpal (TM) joint arthritis
      without the risk of destabilizing the scaphotrapezial (ST) joint. However,
      partial trapeziectomy has been criticized because of concern that ST joint
      arthritis will develop, requiring additional surgery. We hypothesized that
      partial trapeziectomy is a durable treatment for TM joint arthritis, even in
      patients with radiographically abnormal but asymptomatic ST joints. METHODS: We
      evaluated 13 patients (16 thumbs) who underwent a partial trapeziectomy between
      1995 and 2005. Assessment included grip strength, pinch strength, ST joint direct
      palpation, and ST joint stress testing. We classified standardized radiographs of
      the ST joint using a simple scoring system. Subjective data included the
      Disabilities of the Arm, Shoulder, and Hand questionnaire, a pain scale, and a
      satisfaction survey. RESULTS: The length of follow-up averaged 9 years (range, 5
      13 y). No patient had pain at the ST joint with direct palpation or stress
      testing. Radiographs demonstrated a mean ST joint arthritis score of 1,
      indicating mild arthritic changes. Mean grip strength was 28 kg on the operated
      hand and 28 kg on the nonoperated hand. Mean pinch strength was 5 kg on the
      operated hand and 5 kg on the nonoperated hand. Scores on the pain scale averaged
      6 (range, 0-100; 100 = worst). Average Disabilities of the Arm, Shoulder, and
      Hand score was 11 (range, 0-100; 100 = worst). Of 13 patients, 12 were very
      satisfied or extremely satisfied, and 1 was not satisfied. CONCLUSIONS: Partial
      trapeziectomy for TM joint arthritis provides long-lasting relief of symptoms in
      patients with radiographically abnormal but clinically insignificant ST joint
      degeneration. Satisfaction is equivalent to other published series. The
      radiographic appearance of the ST joint did not correlate with symptoms at this
      joint. Unless the patient has symptomatic ST joint arthritis, the ST joint may be
      retained. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22463927
TI  - Incidence of extensor pollicis longus tendon rupture after nondisplaced distal
      radius fractures.
AB  - PURPOSE: The incidence of extensor pollicis longus (EPL) tendon rupture in the
      setting of nondisplaced distal radius fractures is unknown. Extensor pollicis
      longus rupture is a known complication after distal radius fractures and is
      believed to occur more frequently after minimally displaced and nondisplaced
      distal radius fractures. Our study sought to define the incidence of EPL tendon
      rupture after nondisplaced distal radius fractures presenting to a level 1 trauma
      center. METHODS: Using our billing database, we identified distal radius
      fractures presenting to our institution between 2006 and 2009. We reviewed injury
      radiographs to identify fractures in which radiographic measurements were within
      predefined radiographic norms. Two fellowship-trained orthopedic hand surgeons, 1
      fellowship-trained musculoskeletal radiologist, and 1 senior orthopedic surgery
      resident then reviewed these fractures. Only those fractures thought by all 4
      reviewers to be nondisplaced were classified as nondisplaced for the purposes of
      this study. We then reviewed charts of these nondisplaced fractures to identify
      patients who subsequently sustained an EPL tendon rupture. RESULTS: We identified
      3 EPL ruptures out of 61 nondisplaced fractures (5%). These occurred at an
      average of 6.6 weeks after distal radius fractures. CONCLUSIONS: The incidence of
      EPL rupture is higher than previously reported in the literature. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22463928
TI  - Leading change in inflammatory bowel disease. Foreword.

PMID- 22463929
TI  - Changing Crohn's disease management: need for new goals and indices to prevent
      disability and improve quality of life.
AB  - Crohn's disease is a destructive, inflammatory condition. The recent IMPACT
      survey showed that it has a major impact on quality of life including fatigue,
      relationships and employment. Although patients are generally satisfied with
      healthcare services, improvements are needed in the timeliness of diagnosis and
      in communication between patients and healthcare professionals. Evidence is
      lacking about what constitutes quality of care and value to patients. Moving
      forward, value should become the primary goal of healthcare delivery, which is
      likely to require new treatment goals. Indeed, goals are already evolving beyond
      symptom control towards deep remission, which encompasses clinical remission
      together with mucosal healing. The ultimate goals are to prevent bowel damage,
      reduce long-term disability and maintain normal quality of life. A new treat-to
      target approach, with increased monitoring and tighter control of symptoms and
      inflammation, will be needed. This approach will be enabled by use of biomarkers
      and new indices such as the Lemann score, which assesses the extent and severity
      of bowel damage at a specific time-point and over time, and a new disability
      index for patients with inflammatory bowel disease. These principles have been
      adopted for managing rheumatoid arthritis where there is now a focus on treat-to
      target to achieve early remission. Lessons from rheumatoid arthritis can be
      translated to Crohn's disease.

PMID- 22463930
TI  - Implementing changes in clinical practice to improve the management of Crohn's
      disease.
AB  - The introduction of anti-tumour necrosis factor therapies has provided highly
      effective treatments for Crohn's disease, making it possible to significantly
      improve the prognosis of patients. However, neither conventional non-biological
      therapies nor anti-tumour necrosis factor therapies are routinely used to optimum
      effect. There are several reasons for this, including a lack of specific evidence
      to guide common clinical questions and a lack of clearly defined treatment
      targets. This paper suggests some simple changes to the management of Crohn's
      disease that have the potential to significantly improve patient outcomes. A new
      treatment target, 'deep remission', which includes mucosal healing as well as
      clinical remission, may be the first step in defining the successful treatment of
      Crohn's disease; early clinical studies have demonstrated that this is a readily
      achievable target. Initiating appropriate treatment early can increase clinical
      remission rates, improve steroid sparing, induce mucosal healing and prevent
      structural bowel damage, whereby reducing the need for hospitalization and
      surgery. There are also clear indications that modifying treatment based on
      regular objective assessments of disease activity to provide tight disease
      control can improve patient outcomes in a similar way to that observed in
      rheumatoid arthritis. These simple changes to management strategy appear to allow
      the full potential of available treatments to be realized. Clinical studies to
      further define optimized treatment strategies for Crohn's disease are underway
      and will provide future direction.

PMID- 22463931
TI  - What do changes in inflammatory bowel disease management mean for our patients?
AB  - Treatment goals in Crohn's disease are evolving beyond the control of symptoms. A
      treat-to-target approach to management that features earlier initiation of TNF
      antagonist therapy will enable resolution of objective parameters of
      inflammation. The decision to initiate anti-TNF therapy should be based on a
      patient-specific assessment of risks and benefits. This paradigm necessitates a
      complex process, influenced by multiple factors that include the quality of data
      available, physicians' and patients' knowledge of the data, and the preferences
      and values of patients, physicians and society. The potential 'opportunity cost'
      resulting from a delay in initiation of effective therapy, a consideration that
      has been neglected in the past, must also enter into the equation. Our evolving
      approach to the management of Crohn's disease challenges patients to participate
      in the decision-making process and to become an active partner in their care.
      Ideally, this evolution should occur within the context of an enduring
      physician/patient relationship that is based on mutual trust. Motivational
      communication provides a useful technique to improve dialogue and collaboration
      between healthcare professionals and patients, and may help to engage and
      motivate patients to commit to managing their disease.

PMID- 22463932
TI  - The future of inflammatory bowel disease management: combining progress in trial
      design with advances in targeted therapy.
AB  - Anti-tumour necrosis factor antagonists have appreciably improved patient
      outcomes in Crohn's disease, shifting the goals of treatment from control of
      symptoms to clinical remission (Crohn's disease activity index <150) combined
      with mucosal healing - the new concept of 'deep remission'. Achieving deep
      remission brings clinically meaningful benefits, including reduced
      hospitalization and reduced need for surgery. Aspects such as the dose, timing
      and intensification of anti-tumour necrosis factor therapy affect the likelihood
      of achieving deep remission, but definitive evidence on long-term benefits and
      the risk/benefit profile of treatment intensification is needed. A consequence of
      the success of anti-tumour necrosis factor therapies has been a change in the
      disease characteristics of the patient population entering clinical trials.
      Therefore, new clinical study paradigms, such as cluster randomization and
      therapeutic strategy trials, are needed. High placebo response rates and the
      ethics of testing emerging agents against placebo in an era of effective
      therapies are challenges to traditional randomized controlled trials. Overcoming
      these challenges will not only help to optimize anti-tumour necrosis factor
      therapy, but also advance development of emerging treatments for Crohn's disease.

PMID- 22463933
TI  - What changes in inflammatory bowel disease management can be implemented today?
AB  - Innovative ideas are required to improve the management of inflammatory bowel
      disease and to share best practice that can be implemented into clinical practice
      today. The use of biomarkers such as calprotectin to monitor disease progression
      and treatment response could help to improve management of inflammatory bowel
      disease, but several strategies need to be implemented to make this a reality in
      clinical practice. The use of calprotectin as a biomarker and the manipulation of
      the thiopurine pathway to extend the use of current therapies are examples of how
      basic research can translate into patient benefit. Translational research into
      the use of microbiota and predictive factors for response and toxicity to drugs,
      may provide future clinical applications. Global improvement in care in
      inflammatory bowel disease could also be advanced by improving service provision.
      For example, the establishment of 'Centres of Excellence', a global interactive
      inflammatory disease map, and the alignment of processes and standards of care
      within treatment centres may help to achieve better outcomes for patients with
      inflammatory bowel disease. Realization of this goal, as well as a better
      understanding of the aetiology of the disease, may be furthered by collaborative
      efforts between organizations involved in inflammatory bowel disease as well as
      wider collaboration across countries and globally.

PMID- 22463934
TI  - Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel
      composite for guided bone regeneration.
AB  - A novel three-component biomimetic hydrogel composite was successfully prepared
      in this study, which was composed of triblock PEG-PCL-PEG copolymer (PECE),
      collagen and nano-hydroxyapatite (n-HA). The microstructure and thermo
      responsibility of the obtained PECE/Collagen/n-HA hydrogel composite were
      characterized. Scanning electronic microscopy (SEM) showed that the composite
      exhibited an interconnected porous structure. The rheological analysis revealed
      that the composite existed good thermo-sensitivity. In vivo biocompatibility and
      biodegradability was investigated by implanting the hydrogel composite in muscle
      pouches of rats for 3, 7, and 14 days. Moreover, the osteogenic capacity was
      evaluated by means of implanting the composite material in cranial defects of New
      Zealand White rabbits for 4, 12 and 20 weeks. In vivo performances confirmed that
      the biodegradable PECE/Collagen/n-HA hydrogel composite had good biocompatibility
      and better performance in guided bone regeneration than the self-healing process.
      Thus the thermal-response PECE/Collagen/n-HA hydrogel composite had the great
      potential in bone tissue engineering.

PMID- 22463936
TI  - Case reports from Washington University in St. Louis School of Medicine.

PMID- 22463937
TI  - Atresia and sudden sensorineural hearing loss.
AB  - This case study summarizes findings in an adult male, aged 57, who presented to
      the Adult Audiology Clinic with aural atresia in the right ear resulting in a
      conductive hearing loss and a sudden sensorineural hearing loss in the left ear.
      Treatment options included reconstruction surgery in the right ear, bone anchored
      hearing aid in the right ear to overcome the conductive hearing loss, bone
      anchored hearing aid in the left ear for single sided deafness, and intratympanic
      steroid injections in the left ear to salvage hearing. This case study highlights
      that when a patient is educated on all available options the patient is then able
      to make a decision comfortable to him and to help improve his hearing.

PMID- 22463935
TI  - BlyS is up-regulated by hypoxia and promotes migration of human breast cancer
      cells.
AB  - BACKGROUND: The role of B Lymphocyte Stimulator (BLyS) in the survival of
      malignant B cells and the maintenance of normal B cell development and
      homeostasis has been intensively studied in the literature. However, the
      influence of BLyS on breast cancer progression remains unclear. The study aimed
      to investigate the effect of hypoxia on BLyS regulation, cell migratory response
      to BLyS and the possible molecular mechanisms. METHODS: In this study, we
      examined the role of BLyS in the migration of human breast cancer cells by
      transwell assay. We also explored whether BLyS and its receptors expressed in
      human breast cancer cell lines by immunofluorescence and Western Blotting. Then
      we detected the expression level of BLyS in both normoxic and hypoxic conditions
      by real time-PCR and Western Blotting. Pathways involved were confirmed by
      Western Blotting, immunofluorescence, transwell assay and luciferase assay.
      RESULTS: According to our study, the expression level of BlyS was increased in
      human breast cancer cell lines in hypoxic conditions. Up-regulation of this
      protein led to activation and nuclear translocation of NF-kappa B p65. We also
      found that the number of migrated cells was increased in the presence of BLyS and
      inhibition of phosphorylation of Akt attenuated the enhanced migratory response.
      CONCLUSIONS: It suggested that better understanding of BLyS, an
      immunopotentiator, may offer a potential therapeutic target for the treatment of
      human breast cancers. In addition, BLyS promoted breast cancer cells migration,
      underscoring the necessity of appropriate applications of immunopotentiators to
      cancer treatment.

PMID- 22463938
TI  - Sudden sensorineural hearing loss and delayed complete sudden spontaneous
      recovery.
AB  - This is a case report of a 53-yr-old female who experienced sudden sensorineural
      hearing loss (SSNHL) accompanied by roaring tinnitus in her right ear. The
      patient's hearing partially improved in the low frequencies in response to
      intratympanic injections. Given that her hearing loss did not improve further,
      the patient was fitted with a hearing aid to mask the tinnitus and restore a
      sense of balance between the two ears. Approximately 9 mo postonset of the SSNHL,
      a complete spontaneous recovery of hearing occurred. Such a delayed and complete
      recovery is highly unusual. This case highlights that the spontaneous recovery in
      hearing indicates that the pathological cause for the SSNHL involved a process
      that was capable of repair or regeneration, thus ruling out pathologies related
      to cochlear hair cell destruction or nerve fiber loss. This leaves a possibility
      that the event causing the onset of the SSNHL resulted in a disruption of the ion
      homeostatic properties of the cochlea via the production of the endocochlear
      potential.

PMID- 22463940
TI  - Auditory brainstem response testing in neurodiagnosis: structure versus function.
AB  - This case report describes a 44-yr-old female referred by an outside facility who
      presented with progressive hearing loss in her left ear. Magnetic resonance
      imaging (MRI) results were normal, but a battery of audiological tests suggested
      neural hearing loss in the left ear. Following diagnosis of left neural hearing
      loss, the patient was successfully fit with a hearing aid on the left ear. This
      case report underlines the importance of using a battery of medical, radiologic,
      and audiological tests in the accurate determination of hearing loss site of
      lesion. Obvious retrocochlear dysfunction was revealed via auditory brainstem
      response (ABR) testing. MRI did not reveal underlying structural abnormality.
      Without the addition of the ABR to the diagnostic test battery, a cochlear
      hearing loss site of lesion would most likely have been diagnosed. Accurate
      diagnosis of hearing loss site of lesion is critical for patient counseling and
      treatment as well as for patient follow-up and monitoring.

PMID- 22463939
TI  - Sequential bilateral cochlear implantation in a patient with bilateral Meniere's
      disease.
AB  - This case study describes a 45-yr-old female with bilateral, profound
      sensorineural hearing loss due to Meniere's disease. She received her first
      cochlear implant in the right ear in 2008 and the second cochlear implant in the
      left ear in 2010. The case study examines the enhancement to speech recognition,
      particularly in noise, provided by bilateral cochlear implants. Speech
      recognition tests were administered prior to obtaining the second implant and at
      a number of test intervals following activation of the second device. Speech
      recognition in quiet and noise as well as localization abilities were assessed in
      several conditions to determine bilateral benefit and performance differences
      between ears. The results of the speech recognition testing indicated a
      substantial improvement in the patient's ability to understand speech in noise
      and her ability to localize sound when using bilateral cochlear implants compared
      to using a unilateral implant or an implant and a hearing aid. In addition, the
      patient reported considerable improvement in her ability to communicate in daily
      life when using bilateral implants versus a unilateral implant. This case
      suggests that cochlear implantation is a viable option for patients who have lost
      their hearing to Meniere's disease even when a number of medical treatments and
      surgical interventions have been performed to control vertigo. In the case
      presented, bilateral cochlear implantation was necessary for this patient to
      communicate successfully at home and at work.

PMID- 22463941
TI  - Challenges in fitting a hearing aid to a severely collapsed ear canal and mixed
      hearing loss.
AB  - BACKGROUND: Collapsed ear canals typically occur when an outside force, such as a
      headset for audiometric testing, is present. However, when a collapsed ear canal
      occurs without external pressure, this creates a challenge not only for
      performing audiometric testing but also for coupling a hearing aid to the ear
      canal. PURPOSE: This case report highlights the challenges associated with
      fitting a hearing aid on a patient with a severe anterior-posterior collapsed ear
      canal with a mixed hearing loss. RESEARCH DESIGN: A 67-yr-old female originally
      presented to Washington University in St. Louis School of Medicine in 1996 with a
      long-standing history of bilateral otosclerosis. She had chronic ear infections
      in the right ear and a severely collapsed ear canal in the left ear and was fit
      with a bone anchored hearing aid (BAHA(r)) on the right side in 2003. However,
      benefit from the BAHA started to decrease due to changes in hearing, and a
      different hearing solution was needed. It was proposed that a hearing aid be fit
      to her collapsed left ear canal; however, trying to couple a hearing aid to the
      collapsed ear canal required unique noncustom earmold solutions. CONCLUSIONS:
      This case study highlights some of the obstacles and potential solutions for
      coupling a hearing aid to a severely collapsed ear canal.

PMID- 22463942
TI  - Pediatric vestibular evaluation: two children with sensorineural hearing loss.
AB  - These two cases illustrate several important areas of vestibular evaluation with
      children. The two case reports represent two children who display very different
      vestibular findings despite having significant sensorineural hearing loss. These
      case reports highlight that pediatric findings can differ significantly from
      adult findings, stressing the importance of comparing pediatric results with
      pediatric normative data. These two cases also highlight that vestibular
      techniques may successfully be adapted for use with hearing-impaired children.
      That is, rotary chair, computerized dynamic posturography, and vestibular evoked
      myogenic potentials can be adapted to use with children, including those who
      demonstrate significant sensorineural hearing loss. Although there is a paucity
      of research and clinical work in this area, some investigators (Eviatar and
      Eviatar, 1977; Buchman et al, 2004; Jacot et al, 2009) have reported very rapid
      recovery from pediatric vestibular deficits. However, it is important for
      audiologists to be aware that techniques may successfully be adapted for children
      and that many children should undergo thorough vestibular evaluation.

PMID- 22463943
TI  - Against the odds: idiopathic sudden sensorineural hearing loss-results from
      delayed treatment.
AB  - A 79-yr-old male was evaluated by the authors 4-6 wk following a rapid decline in
      perceived hearing in the right ear. Initial treatment with self-administered
      external ear canal irrigations and topical antibiotic prescribed by the patient's
      primary care physician resulted in no apparent improvement. The initial hearing
      evaluation revealed a mild-to-severe sloping sensorineural loss above 1000 Hz in
      the left ear and a moderately severe to severe sensorineural loss with a "flat"
      configuration in the right ear. There was normal word recognition in the left
      ear, with no measurable word recognition in the right ear. Initial treatment with
      oral steroids suggested some subjective improvement, and an intratympanic
      dexamethasone injection was performed. A repeat audiogram obtained approximately
      1 mo postinjection showed significant improvement in pure tone thresholds and
      significant improvement in the word recognition score in the right ear. One week
      later a second intratympanic injection was completed, again, with follow-up in 1
      mo. This case report reviews treatment options for idiopathic sudden
      sensorineural hearing loss (ISSNHL), including usual time lines for treatment and
      expected outcomes and the specific treatments and evaluation results for this
      patient for whom delayed treatment was unusually effective.

PMID- 22463944
TI  - Inflammatory state of type II diabetic patients with chronic ulcers in response
      to herbal treatment.
AB  - BACKGROUND: Type II diabetic patients easily develop ulcers over their feet which
      heal with great difficulties and not infrequently, end up in amputations. In the
      quest for innovative means to avoid amputation, herbal medicine has been used in
      China to heal ulcers. METHOD: A randomized placebo controlled clinical trial
      involving 80 patients was conducted to test whether a herbal formula taken orally
      could help to preserve the ulcerated leg. Other parameters measured included
      granulation maturation time, skin temperature and circulation, and tumor necrosis
      factor alpha (TNF-alpha). RESULTS: showed a 85% limb rescue with the herbal
      treatment group showing superiority over placebo group. TNF-alpha decline was
      observed with gradual ulcer healing and the herbal supplement group showed a more
      impressive decline (p=0.037).

PMID- 22463945
TI  - [How to identify physical inactivity in primary care: validation of the Catalan
      and Spanish versions of 2 short questionnaires].
AB  - OBJECTIVE: The Brief Physical Activity Assessment Tool (BPAAT) and the General
      Practice Physical Activity Questionnaire (GPPAQ) are valid and reliable
      assessment tools to identify "inactive" patients in primary care. No similar
      tools exist for the Spanish population. The study aimed to evaluate the
      reliability and validity of the Catalan and Spanish versions (CBPAAT-CGPPAQ;
      CBPAAT-EGPPAQ) of such tools. DESIGN: Validation study of the linguistic and
      cultural adaptation of two questionnaires into Catalan/Spanish. SETTING: Centres
      of Primary Care. PARTICIPANTS: The load for administering the questionnaires was
      evaluated by 7 general practitioners and 44 patients. Construct validity and
      reliability was assessed in 105 patients (58 years old+/-20; 37% men) without any
      contraindication for physical activity (PA). MAIN VARIABLES: After carrying out
      the translation and back-translation, construct validity was assessed against the
      International Physical Activity Questionnaire (IPAQ short form). Reliability was
      assessed administering the questionnaires again within 14 to 28 days. RESULTS:
      The validity of the CBPAAT-EBPAAT showed a moderate percentage agreement,
      correctly classifying over 80% and 83% of the "inactive" cases. Reliability was
      also good, correctly classifying over 86% and 88% of the cases. The validity of
      the CGPPAQ-EGPPAQ showed a moderate percentage agreement, correctly classifying
      over 70% and 60% of the "inactive" cases. Reliability was good, correctly
      classifying over 82% and 72% of the cases. CONCLUSIONS: The CBPAAT-CGPPAQ and
      EBPAAT-EGPPAQ are valid instruments to identify "inactive" patients that should
      receive advice on PA.

PMID- 22463946
TI  - Lead exposure improves the tolerance of Spodoptera litura (Lepidoptera:
      Noctuidae) to cypermethrin.
AB  - Many ecological factors such as heavy metals can affect the tolerance of
      herbivorous insects to chemical insecticide. Spodoptera litura larvae exposed to
      lead (Pb) (0-100 mg kg(-1) in artificial diet) did not inhibit their growth.
      After 96 h of Pb (0-100 mg kg(-1)) exposure, topical application and feeding of
      cypermethrin to S. litura decreased their mortality and increased weight gain.
      Moreover, the mortality of S. litura treated with 25 and 50 mg kg(-1) of Pb for
      five generations was significantly lower than control. In addition, Pb
      accumulation was detected in midgut, fat body, brain and hemolymph, and its
      highest level was in the midgut. Furthermore, there was a significant negative
      correlation between Pb accumulation in fat body and mortality after topical
      application of cypermethrin. After 96 h of Pb exposure, there was increase
      expression of detoxification enzymes (CYP9A39 and CYP6B47) in midgut and fat body
      of S. litura. Therefore, the tolerance of S. litura to cypermethrin is increased
      by Pb exposure at certain concentrations through Pb accumulation in body and the
      increase of CYP9A39 and CYP6B47 expression.

PMID- 22463947
TI  - Influence of amendments on soil arsenic fractionation and phytoavailability by
      Pteris vittata L.
AB  - Increasing availability of soil arsenic is of significance for accelerating
      phytoremediation efficiency of As-polluted sites. The effects of seven
      amendments, i.e., citrate, oxalate, EDTA, sodium polyacrylate (SPA), phosphate
      rock (PR), single superphosphate (SSP), and compost on fractionation and
      phytoavailability of soil As were investigated in lab culture experiment. The
      results showed that the addition of PR, SPA, EDTA or compost to soils
      significantly increased the concentration of NaHCO(3)-extractable As over a 120 d
      incubation period compared with the control (amendment-free) soil. Then, the four
      amendments were selected to add to As-contaminated soil growing Pteris vittata.
      It was concluded that As accumulation by the fern increased significantly under
      the treatments of PR and SPA by 25% and 31%, respectively. For As fractionation
      in soil, SPA increased Fe-As significantly by 51% and PR increased Ca-As
      significantly by 18%, while both the two amendments reduced occluded-As by 16%
      and 19%, respectively. Adding PR and SPA in soil increased the activities of
      urease and neutral phosphatase resulting from the improvement the fertility and
      physical structure of the soil, which benefits plant growth and As absorption of
      P. vittata. The results of the research revealed that both PR and SPA were
      effective amendments for improving phytoremediation of As-contaminated sites by
      P. vittata.

PMID- 22463948
TI  - Effect of vegetative filter strips on herbicide runoff under various types of
      rainfall.
AB  - Narrow vegetative filter strips proved to effectively reduce herbicide runoff
      from cultivated fields mainly due to the ability of vegetation to delay surface
      runoff, promote infiltration and adsorb herbicides. A field trial was conducted
      from 2007 to 2009 in north-east Italy in order to evaluate the effectiveness of
      various types of vegetative filter strips to reduce spring-summer runoff of the
      herbicides mesotrione, metolachlor and terbuthylazine, widely used in maize, and
      to evaluate the effect of the rainfall characteristics on the runoff volume and
      concentration. Results show that without vegetative filter strip the herbicide
      load that reaches the surface water is about 5-6 g ha(-1)year(-1) for metolachlor
      and terbuthylazine (i.e. 0.5-0.9% of the applied rate), confirming that runoff
      from flat fields as in the Po Valley can have a minor effect on the water
      quality, and that most of the risk is posed by a few, or even just one extreme
      rainfall event with a return period of about 25-27 years, causing runoff with a
      maximum concentration of 64-77 MUg L(-1). Mesotrione instead showed rapid soil
      disappearance and was observed at a concentration of 1.0-3.8 MUg L(-1) only after
      one extreme (artificial) rainfall. Vegetative filter strips of any type are
      generally effective and can reduce herbicide runoff by 80-88%. Their
      effectiveness is steady even under severe rainfall conditions, and this supports
      their implementation in an environmental regulatory scheme at a catchment or
      regional scale.

PMID- 22463949
TI  - Very low food security predicts obesity predominantly in California Hispanic men
      and women.
AB  - OBJECTIVE: A high prevalence of food insecurity has persisted in the USA for the
      past two decades. Previous studies suggest that the association between food
      insecurity and obesity may vary by gender and race/ethnicity. We examined whether
      food insecurity was associated with BMI and obesity within gender and
      racial/ethnic groups in a large, diverse sample of low-income adults. DESIGN: A
      cross-sectional analysis of a large population-based health survey. We compared
      the distribution of BMI and obesity by food security levels within gender and
      racial/ethnic categories. SETTING: Data were derived from the 2003-2009 waves of
      the California Health Interview Survey. SUBJECTS: The study sample included 35
      747 non-elderly adults with households <=200 % of the federal poverty level.
      RESULTS: Among Hispanic men, very low food security was associated with a 1.0
      kg/m2 higher BMI (95 % CI 0.3, 1.7 kg/m2) and a 36 % higher prevalence of obesity
      (95 % CI 17, 58 %) after multivariate adjustment. Among Hispanic women, very low
      food security was associated with a 1.1 kg/m2 higher BMI (95 % CI 0.4, 1.9 kg/m2)
      and a 22 % higher prevalence of obesity (95 % CI 8, 38 %). Positive associations
      were also observed for Asian women and multi-racial men. No significant
      associations were observed for non-Hispanic whites, African Americans, Asian men
      or multi-racial women. CONCLUSIONS: Our results suggest that the association of
      food insecurity and obesity is limited to individuals of certain low-income,
      minority racial/ethnic groups. Whether targeted interventions to address food
      insecurity in these individuals may also decrease obesity risk deserves further
      investigation.

PMID- 22463951
TI  - Interval changes of an extrauterine adenomyoma on magnetic resonance imaging.
AB  - Extrauterine adenomyomas are rare tumors that present as uterus-like masses.
      Uterine adenomyomas can show interval changes according to hormone status.
      However, interval changes in imaging studies have not been reported in
      adenomyomas. We report a rare case of an extrauterine adenomyoma showing unique
      interval changes in magnetic resonance imaging.

PMID- 22463952
TI  - Rectus muscle and visceral peritoneum closure at cesarean delivery and
      intraabdominal adhesions.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of the rectus
      muscle and visceral peritoneum closure at cesarean delivery on adhesions. STUDY
      DESIGN: We performed a secondary analysis of a prospective cohort study of women
      who underwent first repeat cesarean delivery. Surgeons scored the severity and
      location of adhesions. Records were abstracted to assess previous surgical
      techniques. RESULTS: The original cohort included 173 patients. Rectus muscle
      closure was associated with fewer combined filmy and dense adhesions overall
      (27.5% vs 46%; P = .04) and fewer dense adhesions overall (17.5% vs 46%; P =
      .001; adjusted odds ratio, [aOR], 0.24; 95% confidence interval [CI], 0.09-0.65),
      particularly from fascia to omentum (aOR, 0.08; 95% CI, 0.007-0.82). Visceral
      peritoneum closure was associated with increased dense fascia-to-omentum
      adhesions (aOR, 15.78; 95% CI, 1.81-137.24). CONCLUSION: Closure of the rectus
      muscles at cesarean delivery may reduce adhesions, and visceral peritoneum
      closure may increase them. Surgical techniques at cesarean delivery should be
      assessed independently, because they may have opposite effects on adhesion
      formation.

PMID- 22463950
TI  - Key questions and answers about pregnancy-associated plasma protein-A.
AB  - Twenty-five years after it was identified as a circulating protein of unknown
      function derived from the placenta, pregnancy-associated plasma protein-A (PAPP
      A) was discovered to be a novel zinc metalloproteinase expressed by a variety of
      cell types. Great progress has been made in understanding the biology of PAPP-A
      and its regulation during recent years, especially in regard to physiological and
      pathophysiological inflammatory injury responses. However, much remains to be
      learned about this complex protein and its potential clinical implications
      outside pregnancy. In this article we address some of the outstanding questions
      about PAPP-A, in particular about its newly emerging role in the insulin-like
      growth factor (IGF) system.

PMID- 22463953
TI  - [Moyamoya disease in children: a case report].
AB  - Moyamoya is an angiogenic disorder and a rare cause of stroke. It is a
      progressive narrowing of cerebral arteries at the base of the brain involving the
      intracerebral portion of the internal carotid arteries, where it leads to
      development of collateral arteries, causing a "cigarette smoke" aspect. Ischemic
      events are more frequent in pediatric pathology, where hemorrhagic manifestations
      account for only 10%. The prognosis is severe, even worse than when onset of
      symptoms is earlier. We present the case of an 8-year-old child, who had
      presented recurrent hemiparesis since the age of 3 years; the brain CT scan and
      magnetic resonance imaging objectified injury sequelae. The MRA revealed stenosis
      of the internal carotid artery consistent with Moyamoya. In conclusion, the
      diagnosis of Moyamoya disease is now accessible to modern brain imaging
      techniques (MRI and MRA), easily achievable in children. The natural course of
      the disease involves the neurological and vital prognosis in young children, due
      to repeated ischemic attacks. Their identification would facilitate early
      diagnosis in order to treat neurosurgically, leading to a better neurological and
      cognitive prognosis.

PMID- 22463954
TI  - [Management of pediatric liver abscess].
AB  - Liver abscess in the pediatric population remains uncommon in developed
      countries, except in cases of septicemia or in children with major debilitating
      diseases, granulocyte dysfunction, or immunosuppression. Although much is known
      about the etiopathogenesis of liver abscess, the gold standard of investigations
      and treatment is still debatable in developing countries. We report the case of a
      6-year-old child living in Reunion Island, with no medical history, presenting
      with right and pyretic abdominal pain in the right upper quadrant. Ultrasound and
      CT scan showed a large hypodense nonenhanced area in segment IV. Final diagnosis
      was, by exclusion, pyogenic liver abscess based on negative serology, recent
      liver lesion, and normal tumor test results, even if blood culture remained
      negative. No percutaneous puncture was done because of positive outcome after 4
      days of antibiotics. Treatment consisted in three intravenous antibiotics
      (ceftriaxone, aminoxide, and metronidazole) until complete biological
      normalization. Ultrasound remained normal 3 months later. Even if liver abscess
      is uncommon in developing countries, the diagnosis must be raised in cases of
      isolated liver tumor with fever. Management in the nonimmunosuppressed child must
      be discussed associating parenteral antibiotic therapy, percutaneous drainage, or
      surgery in very uncommon cases, according to the liver location and first day's
      progression. Etiological investigation such as colonoscopy in adults must be
      adapted to pediatric data.

PMID- 22463955
TI  - [Pseudohypoaldosteronisme type I: a rare cause of failure to thrive].
AB  - We report on a boy, born on term, presenting with a weight loss and a persistent
      failure to thrive after 10 days despite a normal behavior under bottle-feeding.
      The clinical examination was normal and biological assessment revealed
      hyponatremia with hyponatriuria, normal kaliemia and elevated aldosterone values,
      leading to type I pseudohypoaldosteronism diagnosis. Treatment with salt
      supplementation allowed growth improvement. The diagnosis was confirmed by the
      identification of a mutation in the mineralocorticoid receptor. This change was
      also found in several family members.

PMID- 22463956
TI  - [Multicenter nutritional screening in hospitalized children].

PMID- 22463957
TI  - [Pilot study on the participation of parents in the medication reconciliation
      process].
AB  - OBJECTIVE: The aim of this study was to evaluate the medication reconciliation
      process when parents are asked to complete the medication reconciliation form
      (MRF) and to evaluate their participation through a semi-directed questionnaire.
      METHODS: This is a pilot study conducted in the Pediatric Emergency Department at
      the Sainte-Justine University Hospital in November 2010. All patients from triage
      categories III, IV and V recruited by the pharmacist received an explanatory
      guide, an MRF and a pencil. For each MRF completed by parents, we invited them to
      verbally answer questions from a semi-directed questionnaire. We evaluated the
      compliance of MRF (13 criteria per form) and the content of the MRF (five
      criteria per medication order). RESULTS: A total of 160 parents were met and 127
      parents completed the MRF. The proportion of criteria evaluated to be compliant
      varied between 1 % and 87 % for the form and from 14 % to 78 % for the medication
      order. Only 2 % of MRFs complied with all five criteria related to the medication
      order. A majority of parents (83 %) considered the medication reconciliation
      process to be important/very important, a majority of parents (73 %) considered
      the explanatory guide to be useful/very useful, and a majority (77 %) considered
      the labels used per criterion to be clear/very clear. Finally, 75 % of parents
      used only their memory to complete the MRF. DISCUSSION: It is difficult to obtain
      MRFs that comply with all criteria. However, parents' participation is suitable
      and feasible. There is no doubt that an electronic patient record with access to
      the pharmacological profile shared at all steps of the continuum of care is
      necessary to enable an efficient medication reconciliation process.

PMID- 22463958
TI  - [Post-traumatic small-bowel obstruction: two case studies].
AB  - Post-traumatic small-bowel obstructions are rare and late complications following
      blunt abdominal trauma. Timely diagnosis is frequently impeded because of
      nonspecific associated symptoms, and furthermore, the degree of urgency is
      frequently underestimated due to the accidental cause. During the last 6 years
      (2005-2011), we have observed only 2 cases (4 and 10 years old) with post
      traumatic small-bowel obstruction. On admission the patients had a contusion on
      the abdominal wall, duodenal hematoma and a Chance fracture of the lumbar spine
      on the computed tomography (CT) scan. Although early clinical improvement was
      noted, progression of the disorder was observed for the following 15 days like an
      occlusive syndrome (abdominal distension, nausea, emesis). Abdominal ultrasound
      and computed tomography scan revealed small-bowel obstruction. At laparotomy,
      jejunal stenosis was found associated with mesenteric tears, which was resected
      with end-to-end anastomosis. Six to 8 months of follow-up ascertained the
      therapeutic efficacy of the procedure. Post-traumatic small-bowel obstructions
      are rare; the clinical presentation is unspecific and appears with a time lag
      following the trauma. Echography and computed tomography scan can establish both
      the diagnosis and therapeutic choice.

PMID- 22463959
TI  - [Deafness and antero-inferior cerebellar artery's stroke].

PMID- 22463960
TI  - Battle against Alzheimer's disease: the scope and potential value of magnetic
      resonance imaging biomarkers.

PMID- 22463961
TI  - Altered excitation-inhibition balance in the brain of patients with diabetic
      neuropathy.
AB  - RATIONALE AND OBJECTIVES: To assess differences in excitatory
      (glutamate/glutamine or Glx) and inhibitory (gamma-Aminobutyric acid or GABA)
      neurotransmitter levels using MR spectroscopy in pain processing regions of the
      brain in patients diabetic neuropathy (DN) and positive sensory symptoms and age
      matched healthy control (HC) subjects. MATERIALS AND METHODS: Seven diabetic
      patients (5 males, 2 females, mean age = 57.0 +/- 8.5 years) with confirmed DN
      and positive sensory symptoms and 7 age and sex matched HC subjects (mean age =
      57.7 +/- 3.2 years) underwent 3 Tesla MR spectroscopy. Glx and GABA levels were
      quantified in the right anterior and posterior insula, anterior cingulate cortex
      and right thalamus. RESULTS: Mean Glx levels were significantly higher and mean
      GABA levels were significantly lower within the posterior insula in the DN
      patients compared to HC (P = 0.005 and 0.012 respectively). CONCLUSIONS: This
      pilot data demonstrates an excitatory/inhibitory neurotransmitter imbalance in
      the brain of in patients with DN and positive sensory symptoms compared to pain
      free HC subjects.

PMID- 22463962
TI  - Pre-residency publication rate strongly predicts future academic radiology
      potential.
AB  - RATIONALE AND OBJECTIVES: Radiology resident selection committees often favor
      candidates with strong academic potential. The aim of this study was to determine
      if preresidency academic productivity of current radiologists was predictive of
      subsequent of future academic performance. MATERIALS AND METHODS: The academic
      productivity of all radiology residents trained between 1975 and 2005 at the
      authors' institution was assessed through identification of their publication
      histories, National Institutes of Health funding statuses, and Hirsch indexes (h
      indexes). These metrics were correlated with numbers of publications generated
      prior to beginning radiology residency and grouped accordingly (group 0, none
      prior to residency; group 1, one publication; and group 2, more than one
      publication). Academic productivity metrics of the different groups were compared
      using one-way analysis of variance and chi(2) analysis. Spearman's rho
      coefficient was used to evaluate correlations between the number of preresidency
      publications and subsequent productivity. RESULTS: A cohort of 269 residents was
      included in this study. Group 0 comprised 182 of the 269 residents (68%), while
      groups 1 and 2 comprised 27 (10%) and 60 (22%) residents, respectively. Rates of
      subsequent publication, mean h-index, and National Institutes of Health funding
      statuses were significantly higher in group 2 compared to both groups 0 and 1 (P
      < .0001 for each metric). Preresidency publication volume was significantly
      correlated with future publication performance (rho = 0.3977, P < .0001), mean h
      index (rho = 0.3086, P < .0001), and National Institutes of Health funding status
      (rho = 0.4916, P < .0001). CONCLUSIONS: Radiology residency candidates with
      multiple publications are more likely to achieve future academic success compared
      to candidates with one or zero publications.

PMID- 22463963
TI  - Like brothers.

PMID- 22463964
TI  - Unilateral paralysis associated with profound hypokalemia.
AB  - Unilateral paralysis is rarely reported to be primary presentation of severe
      hypokalemia. We describe a 24-year-old woman who presented to the emergency
      department with sudden onset of right-sided weakness. Neurologic examination
      revealed diminished muscle strength and tendon reflexes over the right limbs.
      Computed tomography of the brain showed no organic brain lesion. However,
      laboratory data showed hypokalemia (K+ 2.0 mmol/L) with metabolic acidosis (HCO3 
      19 mmol/L). She needed a total of 260 mmol K+ to achieve complete recovery of
      muscle strength at a serum K+ level of 3.2 mmol/L and was proved to have distal
      renal tubular acidosis. Severe hypokalemia must be kept in mind as a cause of
      acute unilateral paralysis without organic lesions to avoid unnecessary
      examination and potentially life-threatening complications.

PMID- 22463965
TI  - An electrocardiogram technician improves in-hospital first medical contact-to
      electrocardiogram times: a cluster randomized controlled interventional trial.
AB  - BACKGROUND: In the case of chest pain, the current guidelines require
      electrocardiogram (ECG) recording and patient assessment within 10 minutes upon
      arrival in the emergency department. METHODS: We investigated the effect of an
      ECG technician (ECG-T) on in-hospital first medical contact-to-ECG times (iFMC-to
      ECG) investigated in a cluster randomized, controlled trial. Allocation of
      intervention was concealed. Staff satisfaction and feasibility was defined as a
      secondary outcome. Delays between ECG and the availability of an emergency
      physician and the assessment of ECG were additionally evaluated. RESULTS: A total
      of 163 (44 clusters) and 191 (47 clusters) patients were allocated to control and
      intervention, respectively. Twenty-seven (17%) of 163 patients in the control
      group vs 110 (58%) of 191 patients in the intervention group received ECG
      registration within 10 minutes (risk ratio, 3.40 [2.24-5.15]; P < .001). The iFMC
      to-ECG time was 23 (95% confidence interval [CI], 20-27) minutes for the control
      group vs 9 (95% CI, 8-11) minutes for the intervention group (P < .001). Nursing
      staff judged the feasibility of intervention with a median of 1 (interquartile
      range [IQR], 1-1 (on a scale of 1 [best] to 5 [worst]), perceived workload
      alleviation with a median of 1 (IQR, 1-1), and improvement of quality of care
      with a median of 1 (IQR, 1-2). The ECG-to-EP time was 78 (95% CI, 64-92) seconds,
      and diagnosis was made within 17 (95% CI, 16-18) seconds. CONCLUSIONS: Delays of
      iFMC-to-ECG can be effectively addressed by implementation of an ECG-T. The
      service of an ECG-T is feasible and improves staff satisfaction. Both ECG-to-EP
      time and ECG assessment constitute no relevant delay.

PMID- 22463966
TI  - Risk scores prognostic implementation in patients with chest pain and
      nondiagnostic electrocardiograms.
AB  - BACKGROUND: Several risk scores are available for prognostic purpose in patients
      presenting with chest pain. AIM: The aim of this study was to compare Grace,
      Pursuit, Thrombolysis in Myocardial Infarction (TIMI), Goldman, Sanchis, and
      Florence Prediction Rule (FPR) to exercise electrocardiogram (ECG), decision
      making, and outcome in the emergency setting. METHODS: Patients with
      nondiagnostic ECGs and normal troponins and without history of coronary disease
      underwent exercise ECG. Patients with positive testing underwent coronary
      angiography; otherwise, they were discharged. End point was the composite of
      coronary stenosis at angiography or cardiovascular death, myocardial infarction,
      angina, and revascularization at 12-month follow-up. RESULTS: Of 508 patients
      considered, 320 had no history of coronary disease: 29 were unable to perform
      exercise testing, and finally, 291 were enrolled. Areas under the receiver
      operating characteristic curves for Grace, Pursuit, TIMI, Goldman, Sanchis, and
      FPR were 0.59, 0.68, 0.69, 0.543, 0.66, and 0.74, respectively (P < .05 FPR vs
      Goldman and Grace). In patients with negative exercise ECG and overall low risk
      score, only the FPR effectively succeeded in recognizing those who achieved the
      end point; in patients with high risk score, the additional presence of carotid
      stenosis and recurrent angina predicted the end point (odds ratio, 12 and 5,
      respectively). Overall, logistic regression analysis including exercise ECG,
      coronary risk factors, and risk scores showed that exercise ECG was an
      independent predictor of coronary events (P < .001). CONCLUSIONS: The FPR
      effectively succeeds in ruling out coronary events in patients categorized with
      overall low risk score. Exercise ECG, nonetheless being an independent predictor
      of coronary events could be considered questionable in this subset of patients.

PMID- 22463967
TI  - In-hospital cardiac arrest characteristics and outcome after defibrillator
      implementation and education: from 1 single hospital in Sweden.
AB  - BACKGROUND: Survival after in-hospital cardiac arrest (CA) has been reported to
      be surprisingly low without any major improvement during the last decade. AIMS:
      The aim of this study is to evaluate the clinical impact (delay to defibrillation
      and survival after CA) of an intervention within 1 single hospital (Vasteras,
      Sweden), including (1) a systematic education of all health care professionals in
      cardiopulmonary resuscitation and (2) the implementation of 18 automated external
      defibrillators. METHODS: Information was retrieved from the Swedish National
      Register of Cardiopulmonary Resuscitation. The differences between the 2 calendar
      periods were evaluated by chi(2) and Fisher exact tests. Logistic regression was
      used to control for potential confounders. RESULTS: In total, there were 73 in
      hospital CAs before (12 months) and 133 after (18 months) the intervention. The
      overall delay to defibrillation was not reduced after the intervention, and the
      proportion of survivors to hospital discharge was 26% before and 32% after the
      intervention (P =.51). Cerebral function, however, was improved after the
      intervention (as judged by the cerebral performance categories score; P < .001).
      Thus, the proportion of survivors among all CA patients discharged with a
      cerebral performance scale score of 1 or 2 (good or acceptable cerebral function)
      increased from 20% to 32%. CONCLUSION: An intervention within 1 single hospital
      (systematic training of all health care professionals in cardiopulmonary
      resuscitation and implementation of automated external defibrillators) did not
      reduce treatment delay or increase overall survival. Our results, however,
      suggest indirect signs of an improved cerebral function among survivors.

PMID- 22463968
TI  - The use of i-gel extraglottic airway in a trauma patient.

PMID- 22463969
TI  - Sonographic evaluation of a paralyzed hemidiaphragm from ultrasound-guided
      interscalene brachial plexus nerve block.
AB  - The ultrasound-guided interscalene brachial plexus is becoming increasingly
      popular for anesthesia in the management of upper-extremity injuries by emergency
      physicians. Traditional high-volume injections of local anesthesia will also
      affect the phrenic nerve, leading to temporary paralysis of the ipsilateral
      hemidiaphragm. With direct ultrasound guidance, more precise needle placement
      allows for lower-volume injections that reduce inadvertent spread of local
      anesthetic to the phrenic nerve without decreasing the efficacy of onset of time
      and quality of the block. However, the risk of incidental paralysis of the
      hemidiaphragm is still not eliminated with low-volume intraplexus injections.
      This case highlights this common complication of interscalene brachial plexus
      nerve blocks and demonstrates how emergency physicians can easily use B-mode and
      M-mode ultrasound to evaluate the paralysis of the hemidiaphragm.

PMID- 22463970
TI  - The influence of hemorrhagic shock on ventilation through needle
      cricothyroidotomy in pigs.
AB  - BACKGROUND: The aim of this study was to examine the effects of controlled
      hemorrhage and shock on oxygenation and ventilation using needle
      cricothyroidotomy and jet ventilation in an animal model. METHODS: Twenty-four
      male pigs were randomly allocated into 4 groups: SHOCK (animals in hemorrhagic
      shock only), CRICH (animals that underwent needle cricothyroidotomy only),
      SHOCK+CRICH (animals in hemorrhagic shock + needle cricothyroidotomy), and SHAM
      (anesthetized animals submitted to surgical preparation only). All animals were
      surgically prepared and were observed for a period of 40 minutes (T0 - T40).
      Hemodynamic and blood gas variables were compared using analysis of variance and
      Bonferroni post hoc testing at a level of significance of 95%. RESULTS: CRICH and
      SHOCK+CRICH developed respiratory acidosis, with a progressive decrease of
      arterial pH after T20, and they presented a significant increase of PaCO(2)
      levels after T10, when compared with SHAM and SHOCK (P < .001). When SHOCK+CRICH
      was compared with CRICH, it presented a larger increase of PaCO(2) after T10 (P =
      .036) and an even more significant increase after T20 (P = .009). CONCLUSION:
      Hemorrhagic shock anticipated and intensified the retention of carbon dioxide and
      respiratory acidosis during manual jet ventilation through needle
      cricothyroidotomy in comparison with animals with jet ventilation but without
      shock. The results found in this work should be considered in future protocols
      for the assistance of victims of trauma in prehospital settings.

PMID- 22463971
TI  - Heart-type fatty acid-binding protein as a prognostic factor in patients with
      severe sepsis and septic shock.
AB  - OBJECTIVE: This study was performed to evaluate whether heart-type fatty acid
      binding protein (H-FABP) could predict 28-day mortality in patients with severe
      sepsis and septic shock. METHODS: We performed a prospective observational study
      and included consecutive patients with severe sepsis and septic shock. Patients'
      demographic data, Acute Physiology and Chronic Health Evaluation (APACHE) II
      score, and the blood test results including H-FABP concentrations were compared
      between the 28-day survivors and nonsurvivors. The association between the
      concentration of H-FABP and survival was analyzed with multivariate logistic
      regression and Cox proportional hazards regression analyses. The prognostic
      performance of H-FABP was compared with those of the APACHE II score and albumin
      using the area under the receiver operating characteristic curve. RESULTS: Of the
      99 patients, 38 (38%) died. The mortality rate increased with increasing H-FABP
      concentration. In multivariate logistic regression analyses, H-FABP greater than
      40 ng/mL was an independent predictor of mortality compared with H-FABP less than
      7 ng/mL (odds ratios, 9.23; 95% confidence interval, 1.29-65.86). By Cox
      proportional hazards analysis, H-FABP greater than 40 ng/mL was associated with a
      5.57-fold increased risk for death during the 28-day follow-up period (hazard
      ratio, 5.57; 95% confidence interval, 1.20-25.80). The area under the receiver
      operating characteristic curve of H-FABP was 0.739 (95% confidence interval,
      0.640-0.839), which was comparable with those of the APACHE II score and albumin.
      CONCLUSION: The H-FABP was an independent prognostic factor and could be a useful
      biomarker for 28-day mortality in patients with severe sepsis and septic shock.

PMID- 22463972
TI  - Superior vena cava syndrome masquerading as an allergic reaction.
AB  - Patients are often referred to the emergency department for further evaluation,
      yet the astute physician will maintain a broad differential to avoid anchoring on
      prior diagnoses. In this case, a 56-year-old man was referred to our emergency
      department from the radiology suite secondary to concerns for an "allergic
      reaction" to prior magnetic resonance imaging contrast. Upon presentation, he was
      noted to have facial swelling with ruddy appearance and vascular congestion
      extending to the midchest region; no airway compromise or dyspnea was noted. He
      had a smoking history and recent diagnosis of brain mass, which, combined with
      his current appearance,was concerning for superior vena cava syndrome. A chest x
      ray that demonstrated right mediastinal mass was ordered, and a computed
      tomographic scan confirmed compression of the superior vena cava. A brief
      discussion on the history, etiologies, presentation, and evaluation of superior
      vena cava syndrome is discussed.

PMID- 22463973
TI  - A randomized controlled trial of adding intravenous pantoprazole to conventional
      treatment for the immediate relief of dyspeptic pain.
AB  - INTRODUCTION: Acute, severe dyspeptic pain is a common condition in the emergency
      department. Despite the traditional "GI cocktail" (GI indicates
      gastrointestinal), an intravenous (IV) proton pump inhibitor (PPI), a novel acid
      lowering drug, has recently been used to treat this condition. The aim of this
      study was to evaluate the immediate effect of IV pantoprazole in addition to the
      conventional GI cocktail in the relief of severe dyspeptic pain. METHODS: This
      double-blind, randomized, controlled study was conducted in the emergency
      department of an urban tertiary-care hospital from January 2011 to October 2011.
      Selected patients with severe dyspeptic pain were randomized to treatment with a
      placebo, antacid, and antispasmodic (conventional group) or IV pantoprazole,
      antacid, and antispasmodic (pantoprazole group). The self-reported 100-mm visual
      analog scale score, adverse effects, and overall satisfaction were evaluated in
      15-minute intervals for 60 minutes. RESULTS: Eighty-seven eligible cases were
      enrolled in the study. Forty-four and 43 patients were randomized in the
      conventional group and pantoprazole group, respectively. There was no difference
      in the mean 60-minute visual analog scale scores between the treatment groups.
      The rate of "responders," additional drug use, adverse effects, and patient
      satisfaction were similar between the groups. CONCLUSION: Intravenous PPI
      provides no additional benefit over the conventional GI cocktail in the relief of
      acute, severe dyspeptic pain. Because of its neutral effect and higher cost, the
      use of IV PPI to treat such conditions should be discouraged in general clinical
      practice.

PMID- 22463974
TI  - European genetic variants associated with type 2 diabetes in North African Arabs.
AB  - AIMS: Recent genome-wide association studies (GWAS) and previous approaches have
      identified many genetic variants associated with type 2 diabetes (T2D) in
      populations of European descent, but their contribution in Arab populations from
      North Africa is unknown. Our study aimed to validate these markers and to assess
      their combined effects, using large case-control studies of Moroccan and Tunisian
      individuals. METHODS: Overall, 44 polymorphisms, located at 37 validated European
      loci, were first analyzed in 1055 normoglycaemic controls and 1193 T2D cases from
      Morocco. Associations and trends were then assessed in 942 normoglycaemic
      controls and 1446 T2D cases from Tunisia. Finally, their ability to discriminate
      cases from controls was evaluated. RESULTS: Carrying a genetic variant in BCL11A,
      ADAMTS9, IGF2BP2, WFS1, CDKAL1, TP53INP1, CDKN2A/B, TCF7L2, KCNQ1, HNF1A, FTO,
      MC4R and GCK increased the risk of T2D when assessing the Moroccan and Tunisian
      samples together. Each additional risk allele increased the susceptibility for
      developing the disease by 12% (P = 9.0 * 10(-9)). Genotype information for 13
      polymorphisms slightly improved the classification of North Africans with and
      without T2D, as assessed by clinical parameters, with an increase in the area
      under the receiver operating characteristic curve from 0.64 to 0.67 (P = 0.004).
      CONCLUSION: In addition to TCF7L2, 12 additional loci were found to be shared
      between Europeans and North African Arabs. As for Europeans, the reliability of
      genetic testing based on these markers to determine the risk for T2D is low. More
      genome-wide studies, including next-generation sequencing, in North African
      populations are needed to identify the genetic variants responsible for ethnic
      disparities in T2D susceptibility.

PMID- 22463975
TI  - Limbic encephalitis and type 1 diabetes with glutamic acid decarboxylase 65
      (GAD65) autoimmunity: improvement with high-dose intravenous immunoglobulin
      therapy.
AB  - Glutamic acid decarboxylase antibodies (GAD-abs) are an immunological factor
      involved in type 1 diabetes and other diseases involving the central nervous
      system. This report is of a patient with type 1 diabetes and a rare case of non
      paraneoplastic limbic encephalitis mediated by anti-GAD65 antibodies that
      improved with the use of immunosuppressive drugs.

PMID- 22463976
TI  - Microbial air monitoring in operating theatres: experience at the University
      Hospital of Parma.
AB  - BACKGROUND: Microbial air monitoring in operating theatres has been a subject of
      interest and debate. No generally accepted sampling methods and threshold values
      are available. AIM: To assess microbial air contamination in empty and working
      conventionally ventilated operating theatres over a three-year period at the
      University Hospital of Parma, Italy. METHODS: Air sampling was performed in 29
      operating theatres. Both active and passive sampling methods were used to assess
      bacterial and fungal contamination. FINDINGS: In empty theatres, median bacterial
      values of 12 colony-forming units (cfu)/m(3) [interquartile range (IQR) 4-32] and
      1 index of microbial air contamination (IMA) (IQR 0-3) were recorded. In working
      theatres, these values increased significantly (P < 0.001) to 80 cfu/m(3) (IQR 42
      176) and 7 IMA (IQR 4-13). Maximum recorded values were 166 cfu/m(3) and 8 IMA
      for empty theatres, and 798 cfu/m(3) and 42 IMA for working theatres. Combining
      active and passive samplings, fungi were isolated in 39.13% of samples collected
      in empty theatres and 56.95% of samples collected in working theatres. Over the
      three-year study period, bacterial contamination decreased in both empty and
      working theatres, and the percentage of samples devoid of fungi increased. In
      working theatres, a significant correlation was found between the bacterial
      contamination values assessed using passive and active sampling methods (P <
      0.001). CONCLUSION: Microbiological monitoring is a useful tool for assessment of
      the contamination of operating theatres in order to improve air quality.

PMID- 22463977
TI  - Reduced susceptibility to chlorhexidine among extremely-drug-resistant strains of
      Klebsiella pneumoniae.
AB  - BACKGROUND: Over the last decade, extremely-drug-resistant (XDR) strains of
      Klebsiella pneumoniae have emerged worldwide, mainly as a result of patient-to
      patient spread. The predominant clone, sequence type 258 (ST258), is associated
      with high morbidity and mortality, and is a worldwide threat to public health. It
      was hypothesized that reduced susceptibility to chlorhexidine, the most widely
      used hospital disinfectant, may contribute to the endemic nature of this strain.
      AIM: To characterize and compare the susceptibility of the epidemic K. pneumoniae
      clone ST258 and non-epidemic K. pneumoniae clones to chlorhexidine. METHODS: The
      minimum inhibitory concentration (MIC) of chlorhexidine was determined in 126 XDR
      K. pneumoniae clinical isolates using agar dilution. Expression of three
      different efflux pumps -cepA, acrA and kdeA - was investigated in the absence and
      presence of chlorhexidine using quantitative real-time polymerase chain reaction.
      Heteroresistance to chlorhexidine was identified using population analysis.
      FINDINGS: The MIC of chlorhexidine was higher for K. pneumoniae ST258 (N = 70)
      than other K. pneumoniae sequence types (N = 56); 99% of ST258 isolates had MICs
      >32 MUg/mL, compared with 52% of other K. pneumoniae sequence types (P < 0.0001).
      Reduced susceptibility to chlorhexidine appeared to be independent of the
      expression of cepA, acrA and kdeA efflux pumps. Chlorhexidine-resistant
      subpopulations were observed independent of the bacterial sequence type or the
      MIC. CONCLUSIONS: Reduced susceptibility to chlorhexidine may contribute to the
      success of XDR K. pneumoniae as a nosocomial pathogen, and may provide a
      selective advantage to the international epidemic strain K. pneumoniae ST258. The
      heterogeneous nature of chlorhexidine-resistant subpopulations suggests that this
      phenomenon might not be rendered genetically.

PMID- 22463978
TI  - Evaluation of chromogenic meticillin-resistant Staphylococcus aureus media:
      sensitivity versus turnaround time.
AB  - BACKGROUND: Chromogenic media offer the potential for improved detection of
      meticillin-resistant Staphylococcus aureus (MRSA). Incubation times in a clinical
      setting vary, generally between 16 and 48 h. AIM: To investigate the effects of
      incubation time on the performance of commercial chromogenic MRSA media. METHODS:
      We initially compared the early recovery of MRSA isolates from routine screening
      swabs following 16-23 h to that after 22-24 h of incubation using ChromID MRSA
      (bioMerieux). We also compared ChromID MRSA, ChromID MRSA V2 (bioMerieux),
      Brilliance MRSA 2 Agar (Oxoid) and Colorex MRSA (E&O Laboratories Ltd) as
      selective media for 6035 MRSA screening swabs. FINDINGS: Only 303 of 623 (48.6%)
      MRSA isolates detected by this medium after 48 h were recovered after 16-23 h
      compared with 726 of 1018 (71.3%) isolates after 22-24 h. Following
      implementation of the 22-24 h incubation period, 50 (4.4%) isolates exhibiting a
      positive chromogenic reaction gave conflicting coagulase latex and DNase results.
      In 88% of these cases, DNase gave the correct result of non-MRSA. ChromID MRSA
      demonstrated the highest sensitivity overall at 93.2%, followed by Colorex MRSA
      Agar (87.1%), ChromID V2 (83.7%) and Brilliance Agar (78.2%). All media exhibited
      specificities of >99.7%. CONCLUSION: Early detection of MRSA using ChromID MRSA
      is best achieved after incubation for 22-24 h. Latex agglutination coagulase
      tests alone should not be relied upon for identification of MRSA isolates from
      this medium. Although ChromID MRSA was deemed the superior medium in terms of
      MRSA recovery, the disadvantages of increased turnaround time (48 vs 24 h) must
      be considered.

PMID- 22463979
TI  - Influenza A/H1N1/2009 outbreak in a neonatal intensive care unit.
AB  - BACKGROUND: Outbreaks of influenza A/H1N1/2009 in neonatal intensive care units
      (NICUs) have been reported only rarely. Annual vaccination of all healthcare
      workers (HCWs) against seasonal influenza is recommended but compliance is low
      and exposure to infected staff as the source of nosocomial outbreaks has been
      described. AIM: To report an outbreak of influenza A/H1N1/2009 in a tertiary
      level NICU that resulted in considerable morbidity. METHODS: When the first
      influenza case was identified, a prospective study was conducted and control
      measures were implemented to reduce the spread of infection throughout the NICU.
      Neonates who developed influenza were treated with oseltamivir, and exposed
      neonates were given prophylaxis with oseltamivir. FINDINGS: Two infected infants
      who were immature by gestational age and birth weight developed pneumonitis
      requiring respiratory support, and a third full-term neonate had a mild
      uncomplicated illness. No significant adverse effects were noted during antiviral
      treatment or prophylaxis. The investigation identified infected HCWs as the
      likely source of the outbreak. There was a very low influenza vaccination rate of
      15% among nursing staff. CONCLUSION: Nosocomial influenza can cause considerable
      morbidity, especially in high risk neonates, and is readily transmissible in the
      NICU setting by unvaccinated staff members who contract influenza. To prevent
      outbreaks, in addition to infection control measures, the implementation of HCW
      vaccination is very important. Oseltamivir treatment was well-tolerated even
      among premature infants and appeared to be effective, because neonates with
      influenza had complete recovery and only one of those who received prophylaxis
      developed the infection.

PMID- 22463980
TI  - Breaking the chain: Rift Valley fever virus control via livestock vaccination.
AB  - Rift Valley fever virus is a mosquito-borne pathogen of livestock and humans that
      causes widespread and devastating outbreaks of severe and often fatal disease
      throughout Africa and portions of the Arabian Peninsula. Outbreaks can involve
      tens to hundreds of thousands of human cases, and millions of livestock. The
      severity of the disease varies by species, but in sheep and cattle 'abortion
      storms', high neonatal (~70%), and adult mortality (20-30%) are features. Human
      cases are generally self-limiting, but severe complications such as hepatitis,
      retinitis, delayed-onset encephalitis, or a hemorrhagic syndrome with a case
      fatality of 10-20% can occur. There are no commercially available human vaccines.
      Livestock provide key ecological links between the Aedes sp. mosquito vector and
      humans. High viremias in livestock lead to spillover of RVFV into other
      anthrophillic vectors (Culex and Anopheles sp. mosquitoes), and, importantly,
      close contact with infected animal tissues and fluids or aborted fetal materials
      from these animals is a major risk factor for severe and lethal human infections.
      Vaccination programs targeting livestock during non-epidemic periods or as an
      early countermeasure against nascent outbreaks could therefore eliminate one of
      the main sources of human infection and limit the overall scope of epidemics. To
      this end, research groups have recently reported novel next generation RVFV
      vaccines that are safe for use in pregnant and young animals. Preventing RVFV
      infection of livestock by vaccination is a key element in breaking the chain of
      human epidemics, and could lead to control of this significant public health
      threat.

PMID- 22463981
TI  - Animal virus discovery: improving animal health, understanding zoonoses, and
      opportunities for vaccine development.
AB  - The characterization of viral genomes has accelerated due to improvement in DNA
      sequencing technology. Sources of animal samples and molecular methods for the
      identification of novel viral pathogens and steps to determine their
      pathogenicity are listed. The difficulties for predicting future cross-species
      transmissions are highlighted by the wide diversity of known viral zoonoses.
      Recent surveys of viruses in wild and domesticated animals have characterized
      numerous viruses including some closely related to those infecting humans. The
      detection of multiple genetic lineages within viral families infecting a single
      host species, phylogenetically interspersed with viruses found in other host
      species, reflects past cross-species transmissions. Numerous opportunities for
      the generation of novel vaccines will arise from a better understanding of animal
      viromes.

PMID- 22463983
TI  - Genetic architecture in autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is characterized by impairments in reciprocal
      social interaction and communication, and by restricted and repetitive behaviors.
      Family studies indicate a significant genetic basis for ASD susceptibility, and
      genomic scanning is beginning to elucidate the underlying genetic architecture.
      Some 5-15% of individuals with ASD have an identifiable genetic etiology
      corresponding to known chromosomal rearrangements or single gene disorders. Rare
      (<1% frequency) de novo or inherited copy number variations (CNVs) (especially
      those that affect genes with synaptic function) are observed in 5-10% of
      idiopathic ASD cases. These findings, coupled with genome sequencing data suggest
      the existence of hundreds of ASD risk genes. Common variants, yet unidentified,
      exert only small effects on risk. Identification of ASD risk genes with high
      penetrance will broaden the targets amenable to genetic testing; while the
      biological pathways revealed by the deeper list of ASD genes should narrow the
      targets for therapeutic intervention.

PMID- 22463982
TI  - Accessing naive human pluripotency.
AB  - Pluripotency manifests during mammalian development through formation of the
      epiblast, founder tissue of the embryo proper. Rodent pluripotent stem cells can
      be considered as two distinct states: naive and primed. Naive pluripotent stem
      cell lines are distinguished from primed cells by self-renewal in response to LIF
      signaling and MEK/GSK3 inhibition (LIF/2i conditions) and two active X
      chromosomes in female cells. In rodent cells, the naive pluripotent state may be
      accessed through at least three routes: explantation of the inner cell mass,
      somatic cell reprogramming by ectopic Oct4, Sox2, Klf4, and C-myc, and direct
      reversion of primed post-implantation-associated epiblast stem cells (EpiSCs). In
      contrast to their rodent counterparts, human embryonic stem cells and induced
      pluripotent stem cells more closely resemble rodent primed EpiSCs. A critical
      question is whether naive human pluripotent stem cells with bona fide features of
      both a pluripotent state and naive-specific features can be obtained. In this
      review, we outline current understanding of the differences between these
      pluripotent states in mice, new perspectives on the origins of naive pluripotency
      in rodents, and recent attempts to apply the rodent paradigm to capture naive
      pluripotency in human cells. Unraveling how to stably induce naive pluripotency
      in human cells will influence the full realization of human pluripotent stem cell
      biology and medicine.

PMID- 22463984
TI  - Old and new diagnostic approaches for Q fever diagnosis: correlation among
      serological (CFT, ELISA) and molecular analyses.
AB  - The objective of this study was to evaluate the performance of the complement
      fixation test (CFT) with respect to ELISA for the serological diagnosis of Q
      fever and to assess the role of serology as a tool for the identification of the
      shedder status. During 2009-2010, sera from 9635 bovines and 3872 small ruminants
      (3057 goats and 815 sheep) were collected and analyzed with CFT and ELISA. In
      addition, 2256 bovine, 139 caprine and 72 ovine samples (individual and bulk tank
      milk samples, fetuses, vaginal swabs and placentae) were analyzed with a real
      time PCR kit. The relative sensitivity (Se) and specificity (Sp) of CFT with
      respect to ELISA were Se 26.56% and Sp 99.71% for cattle and Se 9.96% and Sp
      99.94% for small ruminants. To evaluate the correlation between serum-positive
      status and shedder status, the ELISA, CFT and real-time PCR results were
      compared. Due to the sampling method and the data storage system, the analysis of
      individual associations between the serological and molecular tests was possible
      only for some of the bovine samples. From a statistical point of view, no
      agreement was observed between the serological and molecular results obtained for
      fetus and vaginal swab samples. Slightly better agreement was observed between
      the serological and molecular results obtained for the individual milk samples
      and between the serological (at least one positive in the examined group) and
      molecular results for the bulk tank milk (BTM) samples. The CFT results exhibited
      a better correlation with the shedder status than did the ELISA results.

PMID- 22463986
TI  - [Histological techniques in oncodermatology].
AB  - The skin oncology or "oncodermatology" requires a surgical treatment in most
      cases. For some surgeons, the oncodermatology takes a very important part of
      their practice. In the course of diagnostic and therapeutic of skin lesions, the
      pathologist plays now an essential role. He will guide our surgery. The
      techniques used by this specialist are numerous. Therefore, the objective of this
      paper is to review the different histological methods used to improve our
      management of skin tumors.

PMID- 22463985
TI  - Pain-related somatosensory evoked potentials and functional brain magnetic
      resonance in the evaluation of neurologic recovery after cardiac arrest: a case
      study of three patients.
AB  - This case series investigates whether painful electrical stimulation increases
      the early prognostic value of both somatosensory-evoked potentials and functional
      magnetic resonance imaging in comatose patients after cardiac arrest. Three
      single cases with hypoxic-ischemic encephalopathy were considered. A
      neurophysiological evaluation with an electroencephalogram and somatosensory
      evoked potentials during increased electrical stimulation in both median nerves
      was performed within five days of cardiac arrest. Each patient also underwent a
      functional magnetic resonance imaging evaluation with the same neurophysiological
      protocol one month after cardiac arrest. One patient, who completely recovered,
      showed a middle latency component at a high intensity of stimulation and the
      activation of all brain areas involved in cerebral pain processing. One patient
      in a minimally conscious state only showed the cortical somatosensory response
      and the activation of the primary somatosensory cortex. The last patient, who was
      in a vegetative state, did not show primary somatosensory evoked potentials; only
      the activation of subcortical brain areas occurred. These preliminary findings
      suggest that the pain-related somatosensory evoked potentials performed to
      increase the prognosis of comatose patients after cardiac arrest are associated
      with regional brain activity showed by functional magnetic resonance imaging
      during median nerves electrical stimulation. More importantly, this cases report
      also suggests that somatosensory evoked potentials and functional magnetic
      resonance imaging during painful electrical stimulation may be sensitive and
      complementary methods to predict the neurological outcome in the acute phase of
      coma. Thus, pain-related somatosensory-evoked potentials may be a reliable and a
      cost-effective tool for planning the early diagnostic evaluation of comatose
      patients.

PMID- 22463987
TI  - [Management of patients with squamous cell carcinoma of the skin].
AB  - Recurrence, metastasis and mortality due to squamous cell carcinoma are all most
      often linked to late or inappropriate management and/or aggressive histological
      types. In consequence, clear guidelines for management are necessary. The aim of
      this article is to detail clinical management of squamous cell carcinomas based
      on the official guidelines.

PMID- 22463988
TI  - [Preoperative computed tomographic angiography and perforator flaps: a
      standardization of the protocol].
AB  - INTRODUCTION: Perforator flaps have an increasing role in reconstructive surgery.
      The preoperative analysis of perforator arteries enables the precise
      identification of their caliber and course, and so to select the optimal one(s),
      in order to improve the flap's design therefore reducing operating time. This
      study aims to propose a standardized protocol of computed tomographic angiography
      (CTA) before DIEAP flap, ALT flap, TAP flap and SGAP flap. MATERIALS AND METHODS:
      This study focuses on CTA before conducting a perforator flap. Together with
      radiologists, a CTA protocol has been developed. It specifies the patient's
      positioning, the intravenous contrast's concentration, flow rate, acquisition
      start and slice thickness as well as techniques used for mapping and 3D
      reconstruction. RESULTS: Patient positioning must be the same as the operating
      positioning during acquisition. His skin should be free of any cloth, clothing or
      bandages. The intravenous contrast must have a concentration between 350 and
      400mg/ml for a flow rate of 4 ml/sec and its injection followed by a rincure with
      30 ml of saline water. The region of interest (ROI) should be defined for each
      flap. Its definition makes it to follow the contrast's progression through it.
      Acquisition begins when the contrast bolus arrives at the ROI. Slice thickness
      should be of 0.625 mm. CONCLUSION: CTA gives information on the caliber and the
      septal or intramuscular course of perforator as well as on its source vessel. By
      making a mapping of perforators, it prepares surgical procedure and dissection.
      The CTA protocol enhances reliability of perforator flaps.

PMID- 22463989
TI  - [Trends in systemic antifungal use in critically ill patients. Multicenter
      observational study, 2006-2010].
AB  - INTRODUCTION: There are limited data about the use of antifungal agents (AF) in
      critically ill patients and treatment trends since the inclusion of the new
      generation AF. The use of these agents may have a significant influence on the
      development of new resistances. METHODS: Observational prospective study of the
      systemic use of AF in patients admitted to Spanish intensive care units (ICU)
      participating in the ENVIN-HELICS register, from 2006 to 2010. The annual use,
      the indications that led to that use and, the intra-ICU infections, the AF
      employment related to the hospital size, and per 1000 patients/day, were
      compared. RESULTS: Of the 8240 prescriptions for AF, fluconazole and caspofungin
      were the most often employed (55% and 19.5%, respectively). An increase in use
      was observed to the year 2008, with subsequent stabilisation. A decrease in the
      use of fluconazole and an increase in echinocandins consumption was observed over
      time. As regards the intra-ICU infections, the AF were ordered empirically in
      47.9% of the indications. Fluconazole was more frequently used in medium size
      hospitals than in the large ones (60.4% versus 53.3%; P=.036) and the opposite
      occurred in the case of caspofungin (15.8% versus 21.8%; P<.001). Fluconazole was
      more prematurely employed (median 12 days since ICU admission) and the duration
      of the therapy was similar to the other AF (median 8 days). The total therapy
      days were 39.51 per 1000 patient/day, with predominance in fluconazole use (21.48
      per 1000 patients/day). CONCLUSIONS: Fluconazole is the most used antifungal
      agent in critically ill patients in any of the indications, although a
      progressive decrease in its use is observed, with a proportional increase in the
      use of echinocandins.

PMID- 22463990
TI  - Diagnostic yield of instant liquid biphasic Granada medium for group B
      streptococcus detection in pregnant women.

PMID- 22463991
TI  - [Biology of the substrate of atrial fibrillation].
AB  - Atrial fibrillation (AF), the most common sustained cardiac arrhythmia in
      clinical practice, is often associated with progressive dilatation and remodeling
      of the atria which constitute the substrate of the arrhythmia. This atrial
      remodeling is characterized by complex structural and functional alterations of
      the atrial myocardium: short action potentials, heterogeneous refractory periods,
      dystrophic myocytes and interstitial fibrosis which act together to favor local
      conduction bloc, activation of ectopies and the forma-tion of microreentries of
      the electrical excitation. However, the underlying mechanisms of the AF substrate
      are not yet fully understood. The possibility of studying human atrial myocytes
      has led to the identification of ionic currents that contribute to the shortening
      of the action potential and refractory periods during AF. The down-regulation of
      the L-type calcium current plays a central role in this electrical remodeling. It
      results mainly from the dephosphorylation of calcium channels as the consequence
      of an excessive stimulation of atrial myocytes by neurohormones such as the
      atrial natriuretic factor. Abnormal trafficking and targeting of ion channels at
      the plasma membrane has emerged as mechanisms that can contribute to the abnormal
      electrical properties of the atria during AF. Fibrosis is the other feature of
      the AF substrate and it is favored by the atrial hemodynamic overload. Local
      activation of the renin-angiotensin system is involved in the extracellular
      matrix remodeling of the atrial myocardium. Thrombin that accumulates in dilated
      and fibrillating atria could be another important mediator of the myocardial
      structural alterations during AF. This peptide, by binding on its receptor PAR1,
      can modulate several signaling pathways regulating growth and survival of
      myocardial cells. Better understanding of pathogenic factors involved in the
      formation of the AF substrate is crucial for the identification of novel
      biomarkers and therapeutic targets that could be used to improve the diagnostic
      and treatment of AF.

PMID- 22463992
TI  - [Role of cyclic nucleotide phosphodiesterases in the cAMP compartmentation in
      cardiac cells].
AB  - In the light of the knowledge accumulated over the years, it becomes clear that
      intracellular cAMP is not uniformly distributed within cardiomyocytes and that
      cAMP compartmentation is required for adequate processing and targeting of the
      information generated at the membrane. Localized cAMP signals may be generated by
      interplay between discrete production sites and restricted diffusion within the
      cytoplasm. In addition to specialized membrane structures that may limit cAMP
      spreading, degradation of the second messenger by cyclic nucleotide
      phosphodiesterases (PDEs) appears critical for the formation of dynamic
      microdomains that confer specificity of the response to various hormones. This
      review summarizes the main findings that support the cAMP compartmentation
      hypothesis in cardiac cells, with a special emphasis on PDEs. The respective
      roles of the four main cardiac cAMP-PDE families (PDE1 to PDE4) in the
      organization of cAMP microdomains and hormonal specificity in cardiac cells are
      reviewed. The evidence that these PDEs are modified in heart failure is
      summarized, and the implication for the progression of the disease is discussed.
      Finally, the potential benefits that could be awaited from the manipulation of
      specific PDE subtypes in heart failure are presented.

PMID- 22463993
TI  - [Pluripotent stem cells: a cell model for early cardiac development].
AB  - Mouse embryonic stem cell lines were derived three decades ago and allow the
      process of transgenesis and in turn the generation of transgenic mice. In the
      past and still nowadays, these mice as well as more primitive organisms have
      provided models to study the first cell decisions in the embryo. Derivation of
      human embryonic stem cells more than a decade ago has provided a similar cell
      model for human early embryonic development, an issue that could not be addressed
      for obvious ethical reasons which limit research on human embryos. These cells
      allow investigating the genetic and epigenetic mechanisms underlying the first
      cell decisions in the human embryo. Herein, we use cardiogenesis as an example to
      reveal the potential of these cells to better understand the first steps of
      cardiac development.

PMID- 22463994
TI  - [Embryonic stem cells in the treatment of severe cardiac insufficiency].
AB  - The experience accumulated in cardiac cell therapy suggests that regeneration of
      extensively necrotic myocardial areas is unlikely to be achieved by the sole
      paracrine effects of the grafted cells but rather requires the conversion of
      these cells into cardiomyocytes featuring the capacity to substitute for those
      which have been irreversibly lost. In this setting, the use of human pluripotent
      embryonic stem cells has a strong rationale. The experimental results obtained in
      animal models of myocardial infarction are encouraging. However, the switch to
      clinical applications still requires to address some critical issues, among which
      optimizing cardiac specification of the embryonic stem cells, purifying the
      resulting progenitor cells so as to graft a purified population devoid from any
      contamination by residual pluripotent cells which carry the risk of tumorigenesis
      and controlling the expected allogeneic rejection by clinically acceptable
      methods. If the solution to these problems is a pre-requisite, the therapeutic
      success of this approach will also depend on the capacity to efficiently transfer
      the cells to the target tissue, to keep them alive once engrafted and to allow
      them to spatially organize in such a way that they can contribute to the
      contractile function of the heart.

PMID- 22463995
TI  - [Evolution and development of the flower].
AB  - The appearance of the angiosperm flower has been an important morphological
      innovation in plant evolution and is thought to be, at least in part, responsible
      for the evolutionary success of flowering plants. Through studying and comparing
      the molecular basis of flower development in different model species, we can gain
      insights into the diversification of developmental networks that underlie the
      vast array of angiosperm floral morphologies. Floral development is controlled by
      several genes among which MADS-box genes play a crucial role as homeotic genes.
      Indeed, the evolution of the MADS-box transcription factor family appears to have
      played a pivotal role in the development of flower diversity.

PMID- 22463996
TI  - [Sex determination in cucurbits].
AB  - Sex determination in plants leads to the development of unisexual flowers from an
      originally bisexual floral meristem. Cucurbits are not only species of agronomic
      interest but they also represent model species for the study of plant sex
      determination, because of their ability to harbor different sexual types. Such
      sexual forms are controlled by the identity of the alleles at the following loci:
      andromonoecious (a) and gynoecious (g) in melon, or androecious (a), Female (F),
      and Monoecious (M) in cucumber. We firstly showed that the andromonoecious a gene
      in melon encodes for an ACC synthase (CmACS7) and demonstrated that andromonoecy
      results from a mutation in the active site of the enzyme. Expression of the
      active enzyme inhibits the development of the male organs and is not required for
      carpel development. Because the a gene in melon and M gene in cucumber control
      the same sexual transition, monoecy to andromonoecy, we isolated the andromonoecy
      M gene in cucumber using a candidate gene approach in combination with genetic
      and biochemical analysis. We demonstrated the co-segregation of CsACS2, a close
      ortholog of CmACS7, with the M locus, and showed that the cucumber
      andromonoecious phenotype is also due to a loss of ACS enzymatic activity. CsACS2
      is expressed specifically in carpel primordia of female flowers and should play a
      similar role to that of CmACS7 in melon in the inhibition of stamina development.
      Finally, we also showed that the transition from male to female flowers in the
      gynoecious lines results from epigenetic changes in the promoter of a C(2)H (2)
      zinc-finger transcription factor, CmWIP1. This epigenetic change is elicited by
      the insertion of a DNA transposon, which causes the spreading of DNA methylation
      to the CmWIP1 promoter. Expression of CmWIP1 leads to carpel abortion, resulting
      in the development of unisexual male flowers. From all these results, we built a
      model in which CmACS7 and CmWIP1 interact to control the development of male,
      female and hermaphrodite flowers in melon.

PMID- 22463997
TI  - [LEAFY, a master regulator of flower development].
AB  - Flowering plants or angiosperms constitute the vast majority of plant species.
      Their evolutionary success is largely due to the efficiency of the flower as
      reproductive structure. Work performed on model plant species in the last 20
      years has identified the LEAFY gene as a key regulator of flower development.
      LEAFY is a unique plant transcription factor responsible for the formation of the
      earliest floral stage as well as for the induction of homeotic genes triggering
      floral organ determination. But LEAFY is also present in non-flowering plants
      such as mosses, ferns and gymnosperms. Recent studies suggest that LEAFY might
      play a role in cell division and meristem development in basal plants, a function
      that is probably more ancestral than the later acquired floral function.
      Analyzing the evolution of the role and the biochemical properties of this
      peculiar regulator starts to shade light on the mysterious origin of flowering
      plants.

PMID- 22463998
TI  - Superheated high temperature to improve size exclusion chromatography separation
      of polyethylene glycols with chloroform as the mobile phase.
AB  - In our laboratory, chloroform is increasingly required to be used as the mobile
      phase for the size exclusion chromatography (SEC) characterization of
      polyethylene glycol (PEG) derivatives, because some of the derivatives show poor
      solubility in many other solvents. Four types of SEC columns, all based on highly
      cross-linked polystyrene-polydivinylbenzene (PS/PDB) and compatible with
      chloroform, have been tried. However, a problem of using chloroform with all the
      columns tested is that retention might not be rationalized simply based on the
      SEC-mechanism even for the PEG standards. It was found that for the PEG standards
      raising the column temperature can significantly improve the SEC separation. In
      order to take full advantage of the temperature effect on separation, a system
      was developed which enables the SEC to be performed at superheated temperatures,
      i.e., temperatures well above the normal boiling point of the mobile phase. The
      improved SEC separation at elevated temperatures is most likely due to the
      combination of reduced adsorption of PEGs by the stationary phase and increased
      solubility of the solutes in the mobile phase. In this work, the SEC separation
      operated at temperatures above the normal boiling point of the mobile phase was
      called "superheated high temperature SEC".

PMID- 22463999
TI  - Recovery of crocins from saffron stigmas (Crocus sativus) in aqueous two-phase
      systems.
AB  - Crocins are carotenoid derivates that have recently attracted the interest of the
      scientific community due to their nutraceutical properties. Saffron (dry Crocus
      sativus stigmas) is one of the main known sources of crocins. In this study the
      potential use of aqueous two-phase system (ATPS) for the extraction of crocins
      from C. sativus stigmas was evaluated. The partitioning behavior of crocins in
      different types of ATPS (polymer-polymer, polymer-salt, alcohol-salt and ionic
      liquid-salt) was evaluated. Ethanol-potassium phosphate ATPS were selected based
      on their high top phase recovery yield and low cost of system constituents. The
      evaluation and optimization of system parameters rendered conditions (V(R)=3.2,
      ethanol 19.8% (w/w), potassium phosphate 16.5% (w/w), TLL of 25% (w/w), 0.1M NaCl
      and 2% (w/w) of sample load) under which more than 75% of total crocins were
      recovered in the top (ethanol rich) phase, whereas the wasted stigmas accumulated
      in the bottom phase. Lastly, a comparison between an optimized solid-liquid
      extraction using ethanol:water as solvent and ATPS was conducted demonstrating
      that similar yields are achieved with both strategies (76.89 +/- 18% and 79.27 +/
      1.6%, respectively). However, ATPS rendered a higher extraction selectivity of
      1.3 +/- 0.04 mg of crocins for each mg of phenolic compound, whereas ethanolic
      extraction showed a selectivity of 0.87 +/- 0.01. The results reported herein
      demonstrate the potential application of ATPS, particularly ethanol-potassium
      phosphate systems, for the recovery of crocins from C. sativus stigmas.

PMID- 22464000
TI  - Kinetic performance of narrow-bore columns on a micro-system for high performance
      liquid chromatography.
AB  - The kinetic performance of 0.5 mm * 50 mm columns packed with 2.7 MUm Halo-C(18)
      core-shell particles and 3 MUm EP-120-C(18) fully porous particles fitted on an
      Eksigent LC-Express Ultra MUHPLC system were measured. The instrument
      contribution to band broadening was obtained by directly connecting the injection
      valve and the detector cell with a short, narrow PEEKSIL tube. The connections
      between the column and the connecting tubes, the column endfittings and its frits
      contribute to band spreading and are responsible for a significant rear peak
      tailing, even for retained compounds, resulting in a significant loss of
      efficiency. Our results show that the MUHPLC system could outperform the current
      VHPLC systems using 2.1mm I.D. columns packed with 1.7 MUm particles if it were
      using 0.5mm I.D. columns packed with 1 MUm particles, if it could operate at a
      few kbar pressure drop, and if the sum of the contributions of the instrument,
      column endfittings and the column frits to band dispersion were three times
      smaller than it is at present.

PMID- 22464001
TI  - Determination of the uptake and release rates of multifamilies of endocrine
      disruptor compounds on the polar C18 Chemcatcher. Three potential performance
      reference compounds to monitor polar pollutants in surface water by integrative
      sampling.
AB  - The uptake kinetics of 27 emerging pollutants on the polar C18 Chemcatcher have
      been investigated. This investigation determined the sampling rates of 20
      compounds, including 16 endocrine disruptors and 4 pharmaceuticals, which were
      used as overall pollution indicators. Calibrations were completed in a 50-L flow
      through microcosm with continuous renewal of tap water spiked with approximately
      3 MUg/L of each pollutant and with sampling times at 1, 3, 6 and 12h and 1, 3, 7,
      14, 21 and 28 days. Exponential regressions for the accumulation kinetics were
      plotted to confirm the maximum linear uptake times for each molecule using the
      half time of equilibrium (t(1/2)) criteria. Of the compounds tested, 17 were
      accumulated linearly for up to 14 or 21 days with an R(2) above 0.98 for linear
      correlations. The evaluation of the release kinetics of a C18 Chemcatcher spiked
      with 20 deuterated compounds identified 3 potential performance reference
      compounds (PRCs) with exponential desorption rates showing relatively good
      isotropic exchange.

PMID- 22464002
TI  - Quantification of matrix metalloprotease-9 in bronchoalveolar lavage fluid by
      selected reaction monitoring with microfluidics nano-liquid-chromatography-mass
      spectrometry.
AB  - Quantitative protein analysis by liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) in the selected reaction monitoring (SRM) mode was used to quantify
      matrix metalloprotease-9 (MMP-9; ~90 kDa) in bronchoalveolar lavage fluid (BALF)
      from patients having undergone lung transplantation. We developed an SRM assay
      for microfluidics-based nanoLC-MS/MS on a triple quadrupole mass spectrometer
      based on two signature peptides. Samples were prepared by chloroform-methanol
      precipitation followed by trypsin digestion in the presence of stable-isotope
      labeled internal peptide standards. The method allows accurate quantification of
      MMP-9 in BALF with an LLOQ of 2.9 ng/mL and an LLOD of 0.25 ng/mL without the use
      of extensive fractionation or antibodies.

PMID- 22464003
TI  - A matrix effect-free method for reliable quantification of perfluoroalkyl
      carboxylic acids and perfluoroalkane sulfonic acids at low parts per trillion
      levels in dietary samples.
AB  - In recent exposure modeling studies diet has been identified as the dominant
      pathway of human exposure to perfluorooctanoic acid (PFOA) and perfluorooctane
      sulfonic acid (PFOS). However, the paucity of highly sensitive and accurate
      analytical data to support these studies means that their conclusions are open to
      question. Here a novel matrix effect-free method is described for ultra-trace
      analysis of perfluoroalkyl carboxylic acids and perfluoroalkane sulfonic acids in
      dietary samples of varied composition. The method employs ion pair extraction of
      the analytes into methyl tert-butyl ether and subsequent solid phase extraction
      clean-up on Florisil and graphitized carbon. The target compounds are separated
      and detected using ultra performance liquid chromatography coupled to tandem mass
      spectrometry. Special care was taken to avoid procedural blank contamination and
      potential contamination sources were elucidated. The performance of the method
      was validated for five different food test matrices including a duplicate diet
      sample. Method detection limits in the low to sub pgg(-1) range were obtained for
      all target analytes, which is 5-100 times more sensitive than previously reported
      for duplicate diet samples. Total method recoveries were consistently between 50
      and 80% for all analytes in all tested food matrices and effects of co-extracted
      matrix constituents on ionization of the target compounds were found to be
      negligible. The precision of the method (defined as percentage relative standard
      deviation) at concentrations close to the respective method limits of
      quantification was <15% for all analytes. Accurate quantification at ultra-trace
      levels was demonstrated by laboratory control spike experiments. For the first
      time the presence of long-chain PFCAs in duplicate diet samples is reported. The
      method presented here can thus support an improved assessment of human exposure
      from dietary intake for a range of PFCA and PFSA homologues. Re-analysis of
      duplicate diet samples, which had been analyzed earlier using another analytical
      methodology, indicated that dietary intake of PFOA and PFOS may previously have
      been overestimated.

PMID- 22464004
TI  - Simulated moving bed enantioseparation of amino acids employing memory effect
      constrained chromatography columns.
AB  - Teicoplanin aglycone-based chromatography columns (Chirobiotic TAG) enable amino
      acid enantioseparation with aqueous mobile phases, which perfectly accommodates
      the distinct hydrophilicity of most amino acids. Therefore, this stationary phase
      constitutes a promising option in particular for preparative-scale separations
      that require high feed concentrations for economic operation. However, detailed
      studies revealed a solute-related memory effect when this column is subjected to
      high loadings of amino acids, conditions that prevail in SMB operation. High
      loadings yield an activation of the column as indicated by increased retention
      times when comparing finite injection chromatograms obtained before and after the
      column had been subjected to a concentrated amino acid feed. This effect can be
      slowly reversed by flushing the column with solvent devoid of amino acid.
      Obviously, the activation of the stationary phase needs to be accounted for in
      the determination of adsorption isotherms that are used for SMB design. In this
      work we introduce a perturbation method adapted specifically to capture the
      stationary phase behaviour at SMB-like conditions. The adsorption isotherms
      obtained from this method indeed allowed for accurate SMB design of a methionine
      enantioseparation as judged by the very good agreement of experimentally obtained
      and model-predicted purities. Furthermore, SMB operation over 3 days with
      constant purities (besides deviations originating from a dip in temperature) was
      accomplished indicating that the adsorption behaviour in the activated state is
      indeed time invariant and stable long-term SMB operation with these columns is
      principally feasible.

PMID- 22464005
TI  - Prevalence, social contexts, and risks for prepartying among ethnically diverse
      college students.
AB  - Prepartying, also known as pre-gaming, has emerged as a high-risk drinking event
      among U.S. college students. Research on factors related to prepartying behavior
      is in its relative infancy. The present study provides prevalence rates for
      prepartying across ethnic groups and examines how social context (whether
      prepartying took place with primarily male, female, or coed groups) and
      demographic factors may influence prepartying behavior. Participants were
      students from two West Coast universities (N=2546) whom identified as White,
      Asian and Pacific Islander American (APIA), Hispanic/Latino(a), or African
      American. The percentage of students who reported prepartying at least once in
      the past month, as well as the frequency and number of drinks consumed for
      prepartying occasions, varied by ethnic group and sex. A greater proportion of
      White students (60%) reported prepartying than Hispanic/Latino(a) (52%), African
      American (44%), and APIA (37%) students, though Hispanic/Latino(a) students who
      prepartied did so as often and consumed similar amounts of alcohol as White
      prepartiers. Across all ethnic groups, females who reported prepartying in coed
      groups consumed significantly more drinks than those who prepartied in primarily
      female groups. Finally, prepartiers within all ethnic groups consumed more drinks
      per week and experienced a higher number of alcohol-related consequences than non
      prepartiers. The results suggest that future research and prevention programs
      should target prepartying and other high-risk events in at-risk students of
      ethnically diverse backgrounds and also consider the effects of gender in
      prepartying contexts on alcohol use.

PMID- 22464006
TI  - Prevalence and natural course of late-life depression in China primary care: a
      population based study from an urban community.
AB  - BACKGROUND: Primary care is the most promising venue for the management of late
      life depression in China. The current study was designed to establish the
      prevalence of major depressive disorder among older adults in primary care, and
      to examine the correlates, and the natural course of late-life depression over a
      year. METHODS: A sample of 1275 adults aged over 60 years was recruited from a
      primary care clinic in urban China for screening with PHQ-9, and 262 participants
      stratified by PHQ-9 score were interviewed to collect the presence of major
      depressive disorder (MDD), the availability of social support, and physical
      health and functional status. Participants were followed up for 12 months at 3
      month intervals. RESULTS: The estimated prevalence of MDD was 11.3% with the SCID
      interview. Increasing age, female gender, and lower educational level, living
      alone, low support from family, high medical illness burden, and impairment of
      daily function were significantly associated with MDD in later life. Less than 1%
      of these patients received treatments. More than 60% of patients with MDD at
      baseline remained depressed throughout the 12 month follow-up period; and only 3
      patients had been treated during the 12-month follow-up. LIMITATIONS: The
      correlates of late-life depression observed here may not necessarily serve as
      risk factors guiding the development of future prevention strategies. DISCUSSION:
      In an urban Chinese primary care setting, late-life depression was found to be a
      common condition. Few patients with MDD received treatment for their condition,
      and the majority remained depressed over the following year.

PMID- 22464007
TI  - The validity of the Montgomery-Aasberg depression rating scale as a screening
      tool for depression in later life.
AB  - BACKGROUND: The aims of the study were to examine the validity of the MADRS and
      to compare it with the validity of the Cornell Scale for Depression in Dementia
      (CSDD). METHODS: We included 140 patients without dementia, with mean age 81.5
      (sd 7.7) years. Trained psychiatric nurses interviewed all of them using the
      MADRS. In addition, for 70 patients caregivers were interviewed using the CSDD. A
      psychiatrist who had no access to the MADRS or the CSDD results made a diagnosis
      of depression according to the DSM-IV criteria for major depression, and the ICD
      10 criteria was also applied for the 70 patients assessed with the CSDD. RESULTS:
      Twenty-two out of the 140 had depression according to the DSM IV criteria,
      whereas 25 out of 70 had depression according to the ICD-10 criteria. The area
      under the curve (auc) in a receiver operating characteristic analysis was 0.86
      (95% CI 0.79-0.93) for the MADRS using the DSM-IV criteria. The best cut-off
      point was 16/17 with sensitivity of 0.80 and specificity of 0.82. The AUC for the
      CSDD was 0.83 (95% CI 0.71-0.95). The recommended cut-off score on the CSDD of
      7/8 was valid but not the best in this study. LIMITATIONS: The patients were
      diagnosed with a diagnosis of depression by only one psychiatrist, and the
      procedures in the two centres were not exactly the same. CONCLUSIONS: The MADRS
      has good discriminating power to detect depression in elderly persons and should
      be preferred to the CSDD for use with persons without dementia.

PMID- 22464008
TI  - Supportive text messaging for depression and comorbid alcohol use disorder:
      single-blind randomised trial.
AB  - BACKGROUND: Mobile phone text message technology has the potential to improve
      outcomes for patients with depression and co-morbid Alcohol Use Disorder (AUD).
      AIMS: To perform a randomised rater-blinded trial to explore the effects of
      supportive text messages on mood and abstinence outcomes for patients with
      depression and co-morbid AUD. METHODS: Participants (n=54) with a DSM IV
      diagnosis of unipolar depression and AUD who completed an in-patient dual
      diagnosis treatment programme were randomised to receive twice daily supportive
      text messages (n=26) or a fortnightly thank you text message (n=28) for three
      months. Primary outcome measures were Beck's Depression Inventory (BDI-II) scores
      and Cumulative Abstinence Duration (CAD) in days at three months. TRIAL
      REGISTRATION: NCT0137868. RESULTS: There was a statistically significant
      difference in three month BDI-II scores between the intervention and control
      groups; 8.5 (SD=8.0) vs. 16.7 (SD=10.3) respectively after adjusting for the
      baseline scores, F (1, 49)=9.54, p=0.003, eta(p)(2)=0.17. The mean difference in
      change BDI-II scores was -7.9 (95% CI -13.06 to -2.76, Cohen'sd=0.85). There was
      a trend for a greater CAD in the text message group than the control group: 88.3
      (SD=6.2) vs. 79.3 (SD=24.1), t=1.78, df=48, p=0.08. LIMITATIONS: Limitations of
      the study include the small sample size, the potential for loss of rater blinding
      and the lack of long term follow-up to determine the longer term effects of the
      intervention. CONCLUSION: Supportive text messages have the potential to improve
      outcomes for patients with comorbid depression and alcohol dependency syndrome.

PMID- 22464009
TI  - Deficit of cognitive inhibition in depressed elderly: a neurocognitive marker of
      suicidal risk.
AB  - BACKGROUND: Cognitive deficits, in relation to ventral and dorsal prefrontal
      cortex dysfunctions, have been associated with a higher risk of suicidal acts in
      young adult patients. Although a public health concern, much less is known about
      the neurocognitive basis of suicidal behavior in elderly. Here, we aimed at
      assessing alterations in cognitive inhibition, a suspected major mechanism of the
      suicidal vulnerability, in suicidal depressed elderly. METHODS: We compared 20
      currently depressed patients, aged 65 and older who recently attempted suicide to
      20 elderly subjects with a current depression but no personal history of suicide
      attempt and 20 elderly controls. Using an extensive neuropsychological battery,
      we particularly examined different aspects of cognitive inhibition: access to
      relevant information (using the Reading with distraction task), suppression of no
      longer relevant information (Trail Making Test, Rule Shift Cards), and restraint
      of cognitive resources to relevant information (Stroop test, Hayling Sentence
      Completion test, Go/No-Go). RESULTS: After adjustment for age, intensity of
      depression, Mini-Mental State Examination score and speed of information
      processing, suicidal depressed elderly showed significant impairments in all 3
      domains of cognitive inhibition in comparison to both control groups.
      LIMITATIONS: Our results need replication in a larger sample size. CONCLUSIONS:
      Our study suggests that the inability to inhibit neutral information access to
      working memory, restrain and delete irrelevant information may impair the
      patient's capacity to respond adequately to stressful situations subsequently
      leading to an increased risk of suicidal behavior during late-life depression.
      Interventions may be developed to specifically target cognitive impairment in the
      prevention of suicide in depressed elderly.

PMID- 22464010
TI  - Aetiological factors behind adipose tissue inflammation: an unexplored research
      area.
AB  - OBJECTIVE: Despite extensive research into the biological mechanisms behind
      obesity-related inflammation, knowledge of environmental and genetic factors
      triggering such mechanisms is limited. In the present narrative review we present
      potential determinants of adipose tissue inflammation and suggest ways ahead for
      future research in the field. DESIGN: We searched the literature for potential
      determinants of obesity with inflammation through MEDLINE by applying the MeSH
      headings 'obesity' and 'inflammation' in combination with specific terms for a
      series of environmental and genetic factors. RESULTS: Numerous articles reported
      on the association between environmental or genetic factors and respectively
      obesity and inflammation, whereas only a few studies assessed obesity and
      inflammation as a combined outcome. Among suggested determinants for obesity with
      inflammation were Adenovirus-36, the gut microbiota, trans-fatty acids, and the
      four genes FTO, MC4R, TNF-alpha and LEPR. CONCLUSIONS: We present a limited
      number of factors potentially contributing to the development of obesity with
      inflammation, while concluding that overall the area is indeed sparsely
      investigated. We present ideas for future studies that can identify relevant
      aetiological factors. This identification is essential for targeted prevention of
      obesity with inflammation and the clinical consequences thereof.

PMID- 22464011
TI  - Complications nearly double the cost of care after pancreaticoduodenectomy.
AB  - BACKGROUND: Despite considerable data focused on the morbidity of
      pancreaticoduodenectomy (PD), the financial impact of complications has been
      infrequently analyzed. This study evaluates the impact of the most common
      complications associated with PD on the cost of care. Additionally, we identified
      cost centers that were significantly affected by complications. METHODS: A
      retrospective analysis of a prospective database in a network of community-based
      teaching hospitals was performed. All patients (n = 145) who underwent PD were
      included for years 2005 to 2009. Of these, 144 had complete in-hospital cost
      data. Complications were assessed and classified into major and minor categories
      according to Dindo et al. Forty-nine cost centers were analyzed for their
      association with the cost of complications. Univariate and multivariate linear
      regression analyses were performed. Significance was reported for P < .05.
      RESULTS: The median cost for PD was $30,937. Patients with major complications
      had significantly higher median cost compared with those without ($56,224 vs
      $29,038; P < .001). Independent predictors of increased cost included
      reoperation; sepsis; pancreatic fistula; bile leak; delayed gastric emptying; and
      pulmonary, renal, and thromboembolic complications. Cost center analysis showed
      significant added charges for patients with major complications for blood bank
      ($1,018), clinical laboratory ($3,731), a computed tomography scan ($4,742),
      diagnostic imaging ($697), intensive care unit ($4,986), pharmacy ($33,850) and
      respiratory therapy ($1,090) (P < .05, all). CONCLUSIONS: This study identified
      the major complications of PD, which are significantly associated with a higher
      cost. Substantial cost center increases were associated with major complications,
      particularly in pharmacy ($33,850). Measures aimed at limiting complications
      through centralization of care or care pathways may reduce the overall cost of
      care for patients after pancreatic resection.

PMID- 22464012
TI  - Is lavender an anxiolytic drug? A systematic review of randomised clinical
      trials.
AB  - BACKGROUND: Lavender (Lavandula angustifolia) is often recommended for
      stress/anxiety relief and believed to possess anxiolytic effects. AIM: To
      critically evaluate the efficacy/effectiveness of lavender for the reduction of
      stress/anxiety. METHODS: Seven electronic databases were searched to identify all
      relevant studies. All methods of lavender administration were included. Data
      extraction and the assessment of the methodological quality of all included
      trials were conducted by two independent reviewers. RESULTS: Fifteen RCTs met the
      inclusion criteria. Two trials scored 4 points on the 5-point Jadad scale, the
      remaining 13 scored two or less. Results from seven trials appeared to favour
      lavender over controls for at least one relevant outcome. CONCLUSION:
      Methodological issues limit the extent to which any conclusions can be drawn
      regarding the efficacy/effectiveness of lavender. The best evidence suggests that
      oral lavender supplements may have some therapeutic effects. However, further
      independent replications are needed before firm conclusions can be drawn.

PMID- 22464013
TI  - Ethanol extracts of fruiting bodies of Antrodia cinnamomea exhibit anti-migration
      action in human adenocarcinoma CL1-0 cells through the MAPK and PI3K/AKT
      signaling pathways.
AB  - Cancer metastasis is a primary cause of cancer death. Antrodia cinnamomea (A.
      cinnamomea), a medicinal mushroom in Taiwan, has been shown antioxidant and
      anticancer activities. In this study, we first observed that ethanol extract of
      fruiting bodies of A. cinnamomea (EEAC) exerted a concentration-dependent
      inhibitory effect on migration and motility of CL1-0 cells in the absence of
      cytotoxicity. The results of a gelatin zymography assay showed that A. cinnamomea
      suppressed the activity of matrix metalloproteinase (MMP)-2 and MMP-9 in a
      concentration-dependent manner. Western blot results demonstrated that treatment
      with A. cinnamomea decreased the expression of MMP-9 and MMP-2; while the
      expression of the endogenous inhibitors of these proteins, i.e., tissue
      inhibitors of MMP (TIMP-1 and TIMP-2) increased. Two major compounds from EEAC
      codycepin and zhankuic acid A alone and together inhibited MMP-9 and MMP-2
      expressions. Further investigation revealed that A. cinnamomea suppressed the
      phosphorylation of p38, and JNK1/2. A. cinnamomea also suppressed the expressions
      of PI3K and phosphorylation of AKT. This is the first report confirming the anti
      migration activity of this potentially beneficial mushroom against human lung
      adenocarcinoma CL1-0.

PMID- 22464014
TI  - Triptolide inhibits colon-rectal cancer cells proliferation by induction of G1
      phase arrest through upregulation of p21.
AB  - Triptolide, a diterpene triepoxide compound extracted from the traditional
      Chinese medicine herb Tripterygium wilfordii Hook F., is a potential cancer
      chemotherapeutic for tumors. However, the mechanism of anti-proliferative
      mechanism of triptolide in colon cancer cells is not entirely clear. Triptolide
      markedly inhibited HT29 and SW480 cells proliferation in a dose- and time
      dependent manner. Triptolide decreased ERK and AKT phosphorylation, and GABPalpha
      expression in colon cancer cells. Beta-catenin expression and phosphorylation
      were not altered by incubation of triptolide. However, we found that triptolide
      repressed expression of LEF/TCF. Although it did not significantly affect cells
      apoptosis, triptolide induced G1 phase arrest dose-dependently. Further detection
      for the expression of cell cycle-related proteins suggesting that triptolide
      stimulate expression of p21 and repress cyclin A1. Increased p21 binded to
      CDK4/CDK6, therefore blocked function of CDK4/CDK6, and subsequently contribute
      to the G1 arrest. These data suggested that triptolide is a potential agent for
      treatment of colon cancer, and its anti-proliferation effect mainly occur through
      G1 phase arrest.

PMID- 22464015
TI  - [Comparison of three models to predict non-sentinel lymph node status in breast
      cancer patients with metastatic sentinel lymph nodes: a retrospective study of 77
      patients].
AB  - Various statistic predictive models have been developed to predict the status of
      the non-sentinel lymph nodes (NSLN) when the sentinel one was invaded by tumor
      cells in the case of breast invasive carcinoma. The objective of this study was
      to compare the accuracy of three of these statistic models: the MSKCC nomogram,
      the Tenon score and the MDA score. The study was conducted at Croix Rousse
      Hospital, Lyon, France. OBJECTIVE: When sentinel lymph node is invaded by
      metastasis, complete lymph node dissection of the axilla can be avoided using
      statistic predictive models especially when talking about micrometastases and
      moreover about isolated tumor cells in the sentinel lymph node. Over the
      different existing models, we tested the three most used ones to determine the
      model that is most adapted to our everyday practice. METHOD: The study population
      consisted of 77 women with an invasive breast cancer treated by complete axillary
      lymph node dissection for metastatic sentinel lymph node. Over the nine models
      already published, we focused on three of them due to their ease to use as well
      as their good preliminary results: the Memorial Sloan-Kettering Cancer Center
      nomogram (MSKCC), the Tenon score and the M.D Anderson score (MDA). Different
      criteria are used by these models, but all of them take in consideration: tumor
      size, multifocality, tumor type, lymphovascular invasion, hormonal receptors,
      number of sentinel lymph node resected, degree of sentinel lymph node invasion
      (i.e. macrometastasis, micrometastasis or isolated tumor cells) and histologic
      method used to diagnose sentinel lymph node invasion. These scores are validated
      depending on their false negative ratio as well as the proportion of patient
      selected as having a low risk of non-sentinel lymph node invasion. The major
      criterion for the MSKCC score is the calibration that compares the predicted
      likelihood of invasion and the histologically proved one. RESULTS: The rate of
      non-sentinel lymph node invasion was 37.6%. The discrimination of the three
      models was good with an AUC of 0.74 for both MSKCC nomogram and Tenon score and
      of 0.72% for MDA score. MSKCC nomogram was well calibrated (P=0.23). The false
      negative ratio was 0 (CI 95%: 0-18.1%) for MSKCC nomogram, 16.7% (CI 95%: 8.6%
      27.8%) for Tenon score and 16% (CI 95%: 6.8-31%) for MDA score. The percentage of
      patients considered as having a low risk of invasion of the non-sentinel lymph
      node was 20.5% for MSKCC nomogram, 34.7% for MDA score and 47.4% for Tenon score.
      CONCLUSION: MSKCC nomogram seems to be the statistic model that is most adapted
      to the population we studied. To validate the Tenon and MDA score, we should have
      a most important population.

PMID- 22464016
TI  - Early discontinuation of tamoxifen intake in younger women with breast cancer: is
      it time to rethink the way it is prescribed?
AB  - BACKGROUND: Tamoxifen is the main recommended adjuvant hormonal treatment for
      premenopausal women with hormone-responsive early breast cancer. Little data is
      available on compliance and persistence to tamoxifen intake in younger women.
      METHODS: Using the French National Health Insurance System database, we
      constituted a cohort of 288 women who were diagnosed with breast cancer and
      received at least one supply of tamoxifen for breast cancer between September
      2005 and July 2011. Medical records and mailed questionnaires provided
      complementary sources of data. Time to treatment discontinuation and associated
      predictors were studied using techniques for censored data. RESULTS: Among women
      who received a prescription of tamoxifen, 6.1% (16) did not fill any
      prescription. After 2 years of tamoxifen intake, 29.7% (95%confidence interval
      (CI) 24.1-36.4) had discontinued their treatment; after 3 years this percentage
      increased to 39.5% (95% CI 32.9-47.0). The risk of treatment discontinuation rose
      sharply during the 1st year of treatment and remained approximately constant in
      the second year. After multivariate adjustment, tamoxifen discontinuation
      increased significantly with low social support (Hazard Ratio (HR) = 2.1; 95%CI
      1.2-3.4), and self-reporting of non-compliance behaviour (HR = 2.2; 95% CI 1.3
      3.7). CONCLUSION: The consequences of high treatment discontinuation rates in
      younger women with long potential life expectancy may be significant. There is an
      urgent need to acknowledge and tackle compliance issues in the field of oncology,
      unless we are willing to accept inefficient prescriptions of efficacious drugs.

PMID- 22464017
TI  - Complementary and alternative medicine use of women with breast cancer: self-help
      CAM attracts other women than guided CAM therapies.
AB  - OBJECTIVE: Examine stability of use of complementary and alternative medicine
      (CAM) of breast cancer patients, reasons for CAM use, and sociodemographic,
      clinical, and psychological predictors of CAM use. METHODS: CAM use was assessed
      after adjuvant therapy and six months later. Following the CAM Healthcare Model,
      CAM use was divided into use of provider-directed (guided) and self-directed
      (self-help) CAM. Stability and reasons for CAM use were examined with McNemar's
      tests and descriptive statistics. Cross-sectional and longitudinal associations
      between predictors and CAM use were examined with univariate and multivariate
      logistical analyses. RESULTS: Use of provider-directed and self-directed CAM was
      stable over time (N=176). Self-directed CAM was more often used to influence the
      course of cancer than provider-directed CAM. Both were used to influence well
      being. Openness to experience predicted use of provider-directed CAM, while
      clinical distress predicted use of self-directed CAM, after adjusting for other
      predictors. Perceived control did not predict CAM use. CONCLUSION: CAM use is
      stable over time. It is meaningful to distinguish provider-directed from self
      directed CAM. PRACTICE IMPLICATIONS: Providers are advised to plan a 'CAM-talk'
      before adjuvant therapy, and discuss patients' expectations about influence of
      CAM on the course of cancer. Distressed patients most likely need information
      about self-directed CAM.

PMID- 22464018
TI  - Hemophagocytic lymphohistiocytosis in adults: diagnosis and treatment.
AB  - Hemophagocytic lymphohistiocytosis occurring as a primary or acquired disorder is
      a condition of chaotic and uncontrolled immune system stimulation. Cytotoxic
      cells and macrophages cause multiorgan damage, hemophagocytosis, and severe
      systemic inflammation. Clinical manifestations include a fever, organ
      enlargement, and weight loss. Laboratory tests show bicytopenia or pancytopenia,
      cytolysis and cholestasis, serum ferritin elevation, and clotting disorders. The
      reference standard for the diagnosis remains the presence in histological
      specimens of hemophagocytic macrophages, which may be lacking early in the
      disease, leading to diagnostic challenges. Inherited forms produce symptoms in
      early childhood and are fatal in the absence of specific treatment. In adults,
      the clinical spectrum ranges from mild and self-limited hemophagocytic
      lymphohistiocytosis to rapidly fatal multiorgan failure. Many questions remain
      unresolved regarding the diagnosis and treatment in adults. This update is an
      attempt at providing answers.

PMID- 22464019
TI  - Role of lipid lowering therapy and renin angiotensin blockade in outcomes of
      patients with atrial fibrillation.

PMID- 22464020
TI  - IGHV3-21 gene frequency in a Swedish cohort of patients with newly diagnosed
      chronic lymphocytic leukemia.
AB  - The IGHV3-21 gene has been shown to be overrepresented in Scandinavian patients
      with chronic lymphocytic leukemia (CLL). By investigating a population-based
      cohort of 337 Swedish patients with CLL, a lower (6.5%)IGHV3-21 frequency was
      determined relative to our previous hospital-based studies (10.1%-12.7%), yet
      this frequency remained higher compared to other Western CLL cohorts (2.6%-4.1%).
      Furthermore, we confirmed the poor outcome for patients with IGHV3-21 to be
      independent of mutational and stereotypy status. BACKGROUND: Scandinavian
      patients with CLL have shown an overrepresentation of the poor-prognostic IGHV3
      21 gene. Furthermore, approximately 50% of patients with IGHV3-21 carry
      stereotyped B-cell receptors, which implicate antigen selection in
      leukemogenesis. These patients have also been reported to have shorter time to
      progression than patients with nonstereotyped IGHV3-21. MATERIALS AND METHODS: To
      investigate the IGHV3-21 frequency and the clinical impact of IGHV3-21
      stereotypy, 337 newly diagnosed Swedish CLL patients from a population-based
      cohort were analyzed. RESULTS: Interestingly, the IGHV3-21 frequency was indeed
      lower (6.5%) in this indolent patient cohort than in our previous hospital-based
      cohort studies (10.1%-12.7%). Hence, a selection bias of more-aggressive cases
      rendered a higher proportion of IGHV3-21 cases in our original studies.
      Nevertheless, the Swedish IGHV3-21 frequency still remained higher when compared
      with other larger European or American studies (2.6%-4.1%). Finally, we confirmed
      the poor outcome for IGHV3-21 patients to be independent of mutational status and
      found stereotypy to have no impact on survival or time to treatment. CONCLUSION:
      The Swedish geographic bias in IGHV3-21 gene frequency was validated albeit at a
      lower frequency than previously reported. Moreover, no prognostic value could be
      attributed to IGHV3-21 stereotype status.

PMID- 22464021
TI  - How well do Australian shoppers understand energy terms on food labels?
AB  - OBJECTIVE: To investigate nutrition literacy among adult grocery buyers regarding
      energy-related labelling terms on food packaging. DESIGN: Qualitative interviews
      and quantitative surveys to determine shoppers' understanding of energy terms
      ('energy', 'calories' and 'kilojoules') and how energy terms affect perceptions
      of healthiness and intentions to purchase breakfast cereals, muesli bars and
      frozen meals. SETTING: Individual in-depth interviews and surveys in two
      metropolitan supermarkets, Sydney, Australia. SUBJECTS: Australian adults
      (interview n 40, survey n 405) aged 18-79 years. RESULTS: The relationship
      between energy and perceived healthiness of food varied by product type: higher
      energy breakfast cereals were perceived to be healthier, while lower energy
      frozen meals were seen as healthier choices. Likewise, intentions to purchase the
      higher energy product varied according to product type. The primary reason stated
      for purchasing higher energy products was for sustained energy. Participants from
      households of lower socio-economic status were significantly more likely to
      perceive higher energy products as healthier. From the qualitative interviews,
      participants expressed uncertainty about their understanding of kilojoules, while
      only 40 % of participants in intercept surveys correctly answered that kilojoules
      and calories measured the same thing. CONCLUSIONS: Australian consumers have a
      poor understanding of energy and kilojoules and tend to perceive higher energy
      products as healthier and providing sustained energy. This has implications
      regarding the usefulness of industry front-of-pack labelling initiatives and
      quick service restaurant menu labelling that provides information on energy
      content only. Comprehensive and widely communicated education campaigns will be
      essential to guide consumers towards healthier choices.

PMID- 22464022
TI  - [Analysis of disability-free life expectancy over the lifespan: from maturity to
      old age].
AB  - OBJECTIVE: To determine the life stages in which disability-free life expectancy
      is shortened before the age of 70 years. METHOD: A retrospective longitudinal
      analysis was carried out in a cohort of 1,286 non-institutionalized people aged
      from 70 to 74 years old living in metropolitan areas. Disability was measured by
      instrumental and basic activities of daily living. Disability-free life
      expectancy was calculated. The Kaplan-Meier method was used to calculate survival
      probabilities. RESULTS: The incidence of basic disability increased from 50 to 54
      years old and progressively accelerated until the age of 65-69 years old when the
      probability of instrumental disability was slightly higher among men than among
      women (0.23 in men versus 0.19 in women). Disability-free survival was lower
      among women than among men both for all types of disability (LogRank = 5.80; p =
      0.016) and for basic disability (LogRank = 4.315; p = 0.038). CONCLUSIONS: This
      study reveals the importance of instrumental disability for domestic tasks among
      older men. Women had a lower probability of disability-free survival and were
      more likely to be affected by any type of disability as well as by basic
      disability. For both genders, there is a slight decrease in disability-free
      survival from the age of 40 to 60 years. From this age onwards, this decrease
      markedly accelerates.

PMID- 22464023
TI  - [Family care provided by immigrant women and its impact on the quality of care
      and health].
AB  - OBJECTIVE: To understand the effects of care within the family provided by live
      in female immigrants on elderly dependents and their families and the carers
      themselves in Seville (Spain). METHODS: We designed a qualitative study using in
      depth interviews of key informants, immigrant care workers, elderly dependents
      and their families, and discussion groups composed of health professionals. The
      study was carried out in Seville between 2006 and 2008. The observation unit
      consisted of the families of elderly dependents with a live-in female immigrant
      care worker. The analysis units were health, care, dependence, gender, ethnicity
      and social class. Category analysis was carried out using QSR-NUD*ISTVivo1.3.
      After saturation, we triangulated among disciplines, researchers, sources and
      techniques to validate the results. RESULTS: The most important factors for
      carers' health were the migration process and care tasks. Interpersonal
      relationships constituted the principal factor affecting the health of all
      involved. CONCLUSIONS: The care tasks provided by immigrant women, together with
      the migration process, have an important impact on their health. Good and
      egalitarian interpersonal relationships are a protective factor for health.

PMID- 22464024
TI  - [Effect of the introduction of "on demand" nursing shifts on hours of
      absenteeism].
AB  - The objective of this study was to analyze the effect of the introduction of a
      new system of rotating shifts on nursing absenteeism. The novelty of this system
      is that both the time distribution and the planning and allocation of shifts is
      carried out according to the wishes of the participating nurses. This study was
      performed in the Infanta Margarita Hospital (Cordoba, Spain) and the new shift
      system was introduced in the first quarter of 2011. The total number of absolute
      hours of absence decreased from 5551 to 3289 per semester. The implementation of
      this new "on demand" shift system seems to have significantly reduced hours of
      absence. This strategy aims to reconcile nurses' working hours with their
      personal and family lives.

PMID- 22464025
TI  - Gender differences in negative mood states in secondary school students: health
      survey in Catalonia (Spain).
AB  - OBJECTIVE: To determine the prevalence of negative mood states in adolescents
      according to gender, to analyze variability among schools, and to evaluate the
      associated factors. METHODS: A cross-sectional study with a cluster design was
      carried out. We administered the High-school students health survey to a sample
      of 9,340 students (aged 14-16 years) in the third and fourth year of Compulsory
      Secondary Education in Catalonia, Spain, during the 2005-6 academic year. The
      main outcome measure was evidence of a negative mood state. A multilevel logistic
      regression model stratified by gender was used to identify the factors associated
      with negative mood states and to determine variability among distinct schools.
      RESULTS: Approximately 19% of adolescents reported evidence of a negative mood
      state, with a higher prevalence in girls (25%). The most significant factors
      associated with negative mood states were "use of tranquilizers" and "having
      eating disorders" in girls and "not exercising" and "poor self-perception of
      health status" in boys. In both genders, variability was found among schools in
      the prevalence of negative mood states (girls: variance = 0.078; p <0.001; boys:
      variance = 0.079; p = 0.012). CONCLUSIONS: The prevalence of negative mood states
      in adolescent boys and girls was high. Differences were observed between genders
      in the factors related to these health states. The variability observed in the
      prevalence of negative mood states among distinct schools could not be explained
      by the study variables. Our results emphasize the association between the use of
      tranquilizers and negative mood states.

PMID- 22464026
TI  - Psychoactive pharmaceutical residues in the watersheds of Galicia (Spain).
AB  - OBJECTIVE: To monitor the presence of pharmaceutical residues of 14 psychoactive
      drugs belonging to three therapeutic groups in the watersheds of Galicia (Spain).
      METHOD: Five sewage treatment plants were selected in the main cities of Galicia.
      Thirteen psychoactive pharmaceutical compounds and one metabolite were chosen. In
      addition, tap water samples were taken from public places and private residences
      in the selected cities. RESULTS: In all the water samples analyzed, the highest
      concentrations corresponded to the group of anxiolytics. In particular, high
      concentrations of lorazepam were found in river and tap water samples.
      CONCLUSIONS: This investigation demonstrates the presence of psychoactive
      pharmaceuticals in the watersheds of the autonomous region of Galicia and the
      conversion of metabolites to parent compounds. This work also shows the need to
      increase environmental monitoring of watersheds and to improve sewage and
      drinking water treatment processes to remove these pharmaceuticals.

PMID- 22464027
TI  - [The implementation of a clinical practice guideline improves drug-related
      problems].

PMID- 22464028
TI  - Survival, reproduction, and arsenic body burdens in Chironomus riparius exposed
      to arsenate and phosphate.
AB  - Despite the increasing awareness of arsenic (As) contamination in surface waters
      worldwide, little is known about how As alone and in the presence of other
      chemicals affects aquatic insects. Larvae of Chironomus riparius were exposed in
      a laboratory investigation to factorial combinations of 0, 0.13, 2.0, 5.3, and 13
      MUmol As l(-1) and 0, 0.15, and 15 MUmol PO(4) l(-1) throughout development from
      first instar to pupal emergence. The time between male and female emergence
      increased from 1.8+/-0.17 days to 2.9+/-0.34 days with exposure at higher As
      levels. The highest As exposure also decreased the number of eggs per egg mass,
      which may affect population maintenance. For these parameters, there was no
      effect from PO(4), and no interaction between As and PO(4). Total As
      determination of larval and adult tissues was conducted using Hydride Generated
      Atomic Absorption Spectroscopy (HGAAS) and revealed concentrations ranging from
      2.48+/-0.363 to 30.5+/-0.473 MUg/g and 1.03+/-0.286 to 8.97+/-0.662 MUg/g,
      respectively, indicating elimination of approximately 72% of total As body
      burdens between the fourth instar and adult stages. There was no effect of PO(4),
      indicating PO(4) does not alter uptake of As in C. riparius. The potential for
      movement of As to terrestrial systems exists, though trophic transfer may be more
      likely during the aquatic larval stage.

PMID- 22464029
TI  - Predicted toxicity of naphthenic acids present in oil sands process-affected
      waters to a range of environmental and human endpoints.
AB  - Naphthenic acids (NAs) are considered to be a major toxic component of oil sands
      process-affected waters (OSPW) and are also widely used for industrial processes.
      The effects of previously identified NAs (54 in total), together with six
      alkylphenols, were modelled for a range of environmental and human toxicity
      related endpoints using ADMET predictorTM software. In addition to the models,
      experimental CALUX(r) assays were performed on seven tricyclic diamondoid acids.
      Most of the NAs modelled were predicted to have lethal median concentrations
      (LC(50)) >100 MUM for the three aquatic species modelled. Polycyclic acids
      containing a single aromatic ring were predicted to be the most toxic to fathead
      minnows with LC(50)s typically ca 1 MUM. Some of these compounds were also
      predicted to be the most carcinogenic (based on rat and mouse models), possess
      human estrogenic and androgenic activity and potentially disrupt reproductive
      processes. Some aliphatic pentacyclic acids also were predicted to exhibit
      androgenic activity and, uniquely amongst the compounds tested, act as substrates
      for the cytochrome P450 enzyme CYP3A4. Consistent with the models' predictions
      for the tricyclic acids, no estrogenic or androgenic activity was detected by
      ER/AR CALUX(r). Further experimental validation of the predictions should now be
      performed for the compounds highlighted by the models (e.g. priority should
      perhaps be focused on the polycyclic monoaromatic acids and the aliphatic
      pentacyclic acids). If shown to be accurate, these compounds can then be targeted
      for toxicity reduction remediation efforts.

PMID- 22464031
TI  - An analogue trial of inoculation/resilience training for emergency services
      personnel: proof of concept.
AB  - BACKGROUND AND OBJECTIVES: This analogue study served as a proof of concept trial
      for inoculation/resilience training with emergency services personnel. METHODS:
      Eighty people from the general community participated in a randomized controlled
      trial of inoculation training to increase resilience in the mitigation of stress
      and trauma-type symptomatology following a stressful video of paramedics
      attending the scene of a car accident. Participants were randomly allocated to
      one of two conditions: (a) resilience training, where the participants received
      strategies aimed at reducing the negative effects of the event; or (b) a control
      'pragmatic training' condition, where participants received practical training
      about what to do in the event of a car accident. A week later the full video was
      shown. All participants were assessed one month later. RESULTS: Unlike with past
      studies which tested psychological debriefing, analyses revealed that
      inoculation/resilience training did not appear to have deleterious effects on
      psychological distress measures or memory performance. Participants who received
      the resilience training displayed improvements in negative affect (notable trends
      in depression and stress levels) suggesting a more general positive result from
      the intervention than normal 'pragmatic training'. LIMITATIONS: This was an
      analogue trial and a full field trial is warranted. CONCLUSIONS: With
      organisations wishing to engage in resilience training, this analogue study
      suggests that inoculation training at least does no harm and may be beneficial.
      It is, therefore, a viable option for emergency services personnel during pre
      deployment training.

PMID- 22464030
TI  - Principal component analysis optimization of a PM2.5 land use regression model
      with small monitoring network.
AB  - The use of land-use regression (LUR) techniques for modeling small-scale
      variations of intraurban air pollution has been increasing in the last decade.
      The most appealing feature of LUR techniques is the economical monitoring
      requirements. In this study, principal component analysis (PCA) was employed to
      optimize an LUR model for PM2.5. The PM2.5 monitoring network consisted of 13
      sites, which constrained the regression model to a maximum of one independent
      variable. An optimized surrogate of vehicle emissions was produced by PCA and
      employed as the predictor variable in the model. The vehicle emissions surrogate
      consisted of a linear combination of several traffic variables (e.g., vehicle
      miles traveled, speed, traffic demand, road length, and time) obtained from a
      road network used for traffic modeling. The vehicle-emissions surrogate produced
      by the PCA had a predictive capacity greater (R2=.458) than the traffic variable,
      Traffic Demand summarized for a 1 km buffer, with best predictive capacity
      (R2=.341). The PCA-based method employed in this study was effective at
      increasing the fit of an ordinary LUR model by optimizing the utilization of a
      PM2.5 dataset from small-n monitoring network. In general, the method used can
      contribute to LUR techniques in two major ways: 1) by improving the predictive
      power of the input variable, by substituting a principal component for a single
      variable and 2) by creating an orthogonal set of predictor variables, and thus
      fulfilling the no colinearity assumption of the linear regression methods. The
      proposed PCA method, should be universally applicable to LUR methods and will
      expand their economical attractiveness.

PMID- 22464032
TI  - The treatment of medial tibial stress syndrome in athletes; a randomized clinical
      trial.
AB  - BACKGROUND: The only three randomized trials on the treatment of MTSS were all
      performed in military populations. The treatment options investigated in this
      study were not previously examined in athletes. This study investigated if
      functional outcome of three common treatment options for medial tibial stress
      syndrome (MTSS) in athletes in a non-military setting was the same. METHODS: The
      study design was randomized and multi-centered. Physical therapists and sports
      physicians referred athletes with MTSS to the hospital for inclusion. 81 athletes
      were assessed for eligibility of which 74 athletes were included and randomized
      to three treatment groups. Group one performed a graded running program, group
      two performed a graded running program with additional stretching and
      strengthening exercises for the calves, while group three performed a graded
      running program with an additional sports compression stocking. The primary
      outcome measure was: time to complete a running program (able to run 18 minutes
      with high intensity) and secondary outcome was: general satisfaction with
      treatment. RESULTS: 74 Athletes were randomized and included of which 14 did not
      complete the study due a lack of progress (18.9%). The data was analyzed on an
      intention-to-treat basis. Time to complete a running program and general
      satisfaction with the treatment were not significantly different between the
      three treatment groups. CONCLUSION: This was the first randomized trial on the
      treatment of MTSS in athletes in a non-military setting. No differences were
      found between the groups for the time to complete a running program. TRIAL
      REGISTRATION: CCMO; NL23471.098.08.

PMID- 22464033
TI  - A simple approach to prepare monodisperse mesoporous silica nanospheres with
      adjustable sizes.
AB  - A new and facile approach has been developed to prepare monodisperse mesoporous
      silica nanospheres (MMSNs) with controlled particle sizes and pore structures. In
      our approach, MMSNs were synthesized simply in a sodium acetate solution without
      adding any other alkali or alcohol additives. MMSNs have a spherical shape and
      uniform particle sizes, which can be adjusted from 50 to 110 nm by increasing the
      reaction temperature from 40 to 80  degrees C. By performing a subsequent
      hydrothermal treatment (HT) under basic condition (pH=~11.5) at 130  degrees C,
      the mesoporous pore volume and surface area can be enhanced, while keeping the
      mono-dispersion characteristics and the mesopore size almost unchanged. The pore
      sizes of MMSNs can be adjusted from 2.8 to 4.0 nm under acidic solutions by
      changing the HT temperature from 100 to 130  degrees C. The formation process of
      MMSNs has been investigated by transmission electron microscopy (TEM) and
      attenuated total reflection Fourier transform infrared (ATR-FTIR) techniques. A
      spherical micelle templating mechanism is proposed to explain the formation of
      MMSNs in our system, which is different from that of traditional highly ordered
      mesoporous silica nanoparticles (MCM-41).

PMID- 22464034
TI  - Modeling the liquid filling in capillary well microplates for analyte
      preconcentration.
AB  - An attractive advantage of the capillary well microplate approach is the ability
      to conduct evaporative analyte preconcentration. We advance the use of
      hydrophobic materials for the wells which apart from reducing material loss
      through wetting also affords self entry into the well when the droplet size
      reduces below a critical value. Using Surface Evolver simulation without gravity,
      we find the critical diameters D(c) fitting very well with theoretical results.
      When simulating the critical diameters D(c)(G) with gravity included, the
      gravitational effect could only be ignored when the liquid volumes were small
      (difference of 5.7% with 5 MUL of liquid), but not when the liquid volumes were
      large (differences of more than 22% with 50 MUL of liquid). From this, we
      developed a modifying equation from a series of simulation results made to
      describe the gravitational effect. This modifying equation fitted the simulation
      results well in our simulation range (100 degrees <=theta<=135 degrees  and 1
      MUL<=V<=200 MUL). In simulating the condition of multiple wells underneath each
      droplet, we found that having more holes did not alter the critical diameters
      significantly. Consequently, the modifying relation should also generally express
      the critical diameter for multiple wells under a droplet.

PMID- 22464035
TI  - Extended Chamberlain minithoracotomy: a safe and versatile approach for difficult
      lung resections.
AB  - BACKGROUND: We present the perioperative outcomes of patients undergoing an
      anterior "extended Chamberlain" minithoracotomy as an alternative approach to a
      hemi-clamshell sternotomy or extended lateral thoracotomy for safe and reliable
      access to the pulmonary hilum and subsequent anatomic pulmonary resection.
      METHODS: This study is a retrospective review of 162 patients undergoing anatomic
      lung resection through a mini anterior thoracotomy from 2002 to 2010. An 8-cm
      anterior thoracotomy was performed with the patient in a supine position,
      entering the chest through the second intercostal space. The pectoralis muscle
      fibers were split with preservation of the mammary artery medially and the
      thoracoacromial neurovascular bundle laterally. Primary outcome variables
      included hospital course, complications, and mortality rate. RESULTS: The mean
      age was 63.9 (range, 20 to 85 years); female to male ratio was 71:91. Neoadjuvant
      therapy was used in 49 (30.2%) patients. Proposed resections were successful in
      161 of 162 (99%) patients. Conversion to hemi-clamshell was required in 1 patient
      for vascular control. Complications occurred in 48 (29.6%) patients. Three (1.9%)
      perioperative deaths (2 pneumonectomies [6.3%], 1 lobectomy [1.0%]) occurred.
      Median length of stay was 8 days. CONCLUSIONS: The "extended Chamberlain" mini
      anterior thoracotomy provides direct and expeditious, less-invasive access to the
      pulmonary hilum. This approach preserves muscle function and avoids partial
      sternotomy or extended lateral thoracotomy, and their associated incisional
      related morbidity.

PMID- 22464036
TI  - Transcutaneous aortic valve implantation using the left carotid access:
      feasibility and early clinical outcomes.
AB  - BACKGROUND: In some patients, transfemoral, transaxillary, or transapical aortic
      valve implantation is not possible. Thus, carotid artery access may represent a
      safe alternative to those accesses, and even offers certain advantages. In this
      article, we describe aortic valve implantation using the left carotid arterial
      approach and report our initial experience. METHODS: Using a self-expandable
      nitinol based device (CoreValve ReValving system, Medtronic Ltd, Luxembourg), we
      exposed the left carotid artery through a small incision. Arterial puncture and
      initial 6F sheath introduction were achieved through a contraincision. The same
      implantation technique as for transaxillary implantation was used. Progressive
      artery dilatation was achieved using sheaths of increasing diameter. Rapid
      ventricular pacing was used to reduce cardiac output while performing a routine
      aortic balloon valvuloplasty. Only then, an 18F sheath was inserted into the
      carotid artery and pushed down into the ascending aorta. The patients were
      monitored using cerebral oxymetry to assess cerebral perfusion. RESULTS: Twelve
      consecutive patients, at high surgical risk, were implanted and studied
      prospectively. Transfemoral and subclavian catheterization were considered
      unfeasible or at risk of severe complications. Carotid arterial injury did not
      occur in any patient. A transient ischemic attack occurred in 1 patient,
      contralateral to the carotid access. There were no deaths in either
      intraprocedural or during the 30-day follow-up period. CONCLUSIONS: This initial
      experience suggests that left carotid transarterial aortic valve implantation, in
      selected high-risk patients, is feasible and safe with satisfactory short-term
      outcomes.

PMID- 22464037
TI  - Determinants of personal and household hygiene among college students in New York
      City, 2011.
AB  - BACKGROUND: Although several studies have characterized the hygiene habits of
      college students, few have assessed the determinants underlying such behaviors.
      OBJECTIVES: Our study sought to describe students' knowledge, practices, and
      beliefs about hygiene and determine whether there is an association between
      reported behaviors and frequency of illness. METHODS: A sample of 299
      undergraduate students completed a questionnaire assessing demographics, personal
      and household hygiene behaviors, beliefs and knowledge about hygiene, and general
      health status. RESULTS: Variation in reported hygiene habits was noted across
      several demographic factors. Women reported "always" washing their hands after
      using the toilet (87.1%) more than men (65.3%, P = .001). Similarly, freshmen
      reported such behavior (80.4%) more than sophomores (71.9%), juniors (67.7%), or
      seniors (50%, P = .011). Whereas 96.6% of participants thought that handwashing
      was either "very important" or "somewhat important" for preventing disease,
      smaller proportions thought it could prevent upper respiratory infections (85.1%)
      or gastroenteritis (48.3%), specifically. There was no significant relationship
      between reported behaviors and self-reported health status. CONCLUSION: The
      hygiene habits of college students may be motivated by perceptions of socially
      acceptable behavior rather than scientific knowledge. Interventions targeting the
      social norms of incoming and continuing students may be effective in improving
      hygiene determinants and ultimately hygiene practices.

PMID- 22464038
TI  - Seasonal and H1N1 influenza vaccine compliance and intent to be vaccinated among
      emergency medical services personnel.
AB  - BACKGROUND: Only limited data are available on emergency medical technicians'
      (EMT) influenza vaccination compliance. METHODS: A questionnaire was administered
      to St. Louis EMTs during March to June 2011 to assess compliance with the
      2010/2011 and 2009/2010 seasonal and pandemic H1N1 influenza vaccinations,
      factors that predicted uptake of 2010/2011 seasonal influenza vaccine, and intent
      to be vaccinated. RESULTS: In all, 265 EMTs participated. EMTs' attitudes and
      beliefs toward influenza vaccines differed significantly when comparing
      vaccinated to nonvaccinated EMTs. EMTs whose employer had a mandatory vaccination
      policy were significantly more likely to receive the seasonal influenza vaccine
      (100% vs 75.6%, respectively) or the H1N1 vaccine (100% vs 66.8%, respectively)
      compared with those without such a policy (chi(2) = 8.8, P < .001 and chi(2) =
      6.7, P < .01, respectively). In logistic regression controlling for demographics,
      determinants of 2010/2011 seasonal influenza vaccination included belief that
      EMTs should be vaccinated every year, perceived importance of vaccination,
      perception that influenza vaccine has few adverse effects, and past vaccine
      seeking behavior. In logistic regression controlling for demographics,
      determinants of intent to be vaccinated included having the vaccine available on
      site and free of charge and belief that EMTs should be vaccinated every year.
      CONCLUSION: EMT-targeted interventions should be used to increase vaccine
      compliance, including implementing a mandatory vaccination policy and addressing
      EMTs' beliefs and attitudes about vaccine in an education campaign.

PMID- 22464039
TI  - Hospital privacy curtains are frequently and rapidly contaminated with
      potentially pathogenic bacteria.
AB  - BACKGROUND: Privacy curtains are a potentially important site of bacterial
      contamination in hospitals. We performed a longitudinal study to determine the
      prevalence and time course of bacterial contamination on privacy curtains.
      METHODS: Over a 3-week period, swab cultures (n = 180) were obtained twice weekly
      from the leading edge of 43 curtains in 30 rooms in 2 intensive care units and a
      medical ward. Curtains were marked to determine when they were changed.
      Contamination with Staphylococcus aureus, methicillin-resistant S aureus (MRSA),
      Enterococcus spp, vancomycin-resistant enterococcus (VRE), or aerobic gram
      negative rods was determined by standard microbiologic methods. To distinguish
      persistence of pathogens on curtains from recontamination, all VRE and MRSA were
      typed using pulsed-field gel electrophoresis. RESULTS: Twelve of 13 curtains
      (92%) placed during the study showed contamination within 1 week. Forty-one of 43
      curtains (95%) demonstrated contamination on at least 1 occasion, including 21%
      with MRSA and 42% with VRE. Eight curtains yielded VRE at multiple time points: 3
      with persistence of a single isolate type and 5 with different types, suggesting
      frequent recontamination. CONCLUSION: Privacy curtains are rapidly contaminated
      with potentially pathogenic bacteria. Further studies should investigate the role
      of privacy curtains in pathogen transmission and provide interventions to reduce
      curtain contamination.

PMID- 22464040
TI  - Belimumab: review of use in systemic lupus erythematosus.
AB  - BACKGROUND: Belimumab, a monoclonal antibody that inhibits B-lymphocyte
      stimulating protein, was the first biologic agent approved for, and the first
      drug approved in 55 years for, the treatment of systemic lupus erythematosus
      (SLE) by the US Food and Drug Administration (FDA). OBJECTIVE: This article
      reviews the current research on belimumab and provides recommendations on its use
      in the treatment of SLE. METHODS: The Cochrane Library, EBSCO, IPA, MEDLINE, and
      SCOPUS were searched for research published from January 2000 to November 2011,
      using the search terms belimumab, Benlysta, and Lympho-Stat B. Selection criteria
      included peer-reviewed original research articles on the pharmacology,
      pharmacokinetic properties, drug interactions, and clinical efficacy and
      tolerability of belimumab in the treatment of SLE. Abstracts from the annual
      meetings of major rheumatology medical organizations and societies were searched
      and reviewed for new content. Additional information on belimumab was obtained
      from the manufacturer, from the FDA, and from other sources. MEDLINE was also
      used to select clinical studies and therapeutic guidelines on SLE therapy.
      RESULTS: The literature search identified 1 Phase II and 2 Phase III studies that
      compared belimumab (1, 4, and 10 mg/kg/dose IV on days 0, 14, and 28; then every
      28 days) to placebo in patients with active SLE on concurrent therapies. Patients
      with active lupus nephritis or neuropsychiatric lupus were excluded. In a Phase
      II, 52-week study, 24-week mean Safety of Estrogens in Lupus Erythematosus
      National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA
      SLEDAI) scores were decreased by 19.5% with belimumab versus 17.2% with placebo
      (P = NS). Median time to first flare was 67 days with belimumab versus 83 days
      with placebo (P = NS). In seropositive patients, 52-week mean SELENA-SLEDAI
      scores were decreased by 28.8% with belimumab versus 14.2% with placebo (P <
      0.05), and physician's global assessment scores were improved by 32.7% with
      belimumab versus 10.7% with placebo (P < 0.05). Two Phase III studies were
      performed in seropositive SLE patients. In a Phase III, 52-week study, the rates
      of response (a reduction of >=4 points on the SLE Response Index [SRI]) at week
      52 were 51% and 58% with belimumab 1 and 10 mg/kg/dose, respectively, versus 44%
      with placebo (both, P < 0.05). In a Phase III, 76-week study, the rates of
      response, as measured using SRI, at week 52 were 42.8% and 46.5% with belimumab 1
      and 10 mg/kg/dose versus 35.3% with placebo (P = NS and P < 0.001); at 76 weeks,
      response rates were 42.1% and 41.4% with belimumab 1 and 10 mg/kg/dose versus
      33.8% with placebo (P < 0.05 and P = NS). The tolerability data from these
      studies did not suggest any overall differences between belimumab and placebo.
      CONCLUSIONS: Based on the findings from the present review, belimumab appears to
      be efficacious and generally well-tolerated and in the treatment of SLE other
      than lupus nephritis or neuropsychiatric lupus. Additional clinical and economics
      studies are needed to determine the most appropriate place for belimumab in the
      treatment of SLE.

PMID- 22464041
TI  - An innovative device to predict acute hypotension episodes in critically ill
      patients: hypothesis and prototype development.

PMID- 22464042
TI  - Possible different serum IL-4 levels across populations: a reason for dissimilar
      incidence of Th1 and Th2 diseases.
AB  - The incidence of a number of Th1 and Th2 diseases differs across populations.
      Interleukin-4 (IL-4) is a dispensable cytokine for the development of a type 2
      immune response. Studies in which serum IL-4 levels were quantified in a healthy
      control group from some European and Asian countries propose that serum IL-4
      levels may be higher in Asian compared to European countries. A simultaneous
      measurement of serum IL-4 levels in healthy individuals from different
      populations in a reference lab is needed to confirm different IL-4 levels across
      populations. If so, increased IL-4 levels might be an explanation for dissimilar
      incidence of some Th1 and Th2 diseases in different courtiers.

PMID- 22464043
TI  - Pain management in patients with plantar fasciitis: the emerging role of radial
      extracorporeal shockwave therapy.

PMID- 22464044
TI  - Deposition of inhaled particles in the lungs.
AB  - Inhaled medication is the first-line treatment of diseases such as asthma or
      chronic obstructive pulmonary disease. Its effectiveness is related to the amount
      of drug deposited beyond the oropharyngeal region, the place where the deposit
      occurs and its distribution (uniform or not). It is also important to consider
      the size of the inhaled particles, the breathing conditions, the geometry of the
      airways and the mucociliary clearance mechanisms. Currently, mathematical models
      are being applied to describe the deposition of inhaled drugs based on the size
      of the particles, the inspiratory flow and the anatomical distribution of the
      bronchial tree. The deposition of particles in the small airways gets maximum
      attention from pharmaceutical companies and is of great interest as it is related
      with a better control in patients receiving these drugs.

PMID- 22464045
TI  - Pleural ultrasound applications.

PMID- 22464046
TI  - Screening for posttraumatic stress disorder using verbal features in self
      narratives: a text mining approach.
AB  - Much evidence has shown that people's physical and mental health can be predicted
      by the words they use. However, such verbal information is seldom used in the
      screening and diagnosis process probably because the procedure to handle these
      words is rather difficult with traditional quantitative methods. The first
      challenge would be to extract robust information from diversified expression
      patterns, the second to transform unstructured text into a structuralized
      dataset. The present study developed a new textual assessment method to screen
      the posttraumatic stress disorder (PTSD) patients using lexical features in the
      self narratives with text mining techniques. Using 300 self narratives collected
      online, we extracted highly discriminative keywords with the Chi-square algorithm
      and constructed a textual assessment model to classify individuals with the
      presence or absence of PTSD. This resulted in a high agreement between computer
      and psychiatrists' diagnoses for PTSD and revealed some expressive
      characteristics in the writings of PTSD patients. Although the results of text
      analysis are not completely analogous to the results of structured interviews in
      PTSD diagnosis, the application of text mining is a promising addition to
      assessing PTSD in clinical and research settings.

PMID- 22464047
TI  - The relationship between childhood exposure to trauma and intermittent explosive
      disorder.
AB  - There has been a paucity of research linking intermittent explosive disorder
      (IED) to trauma and posttraumatic stress responses, despite evidence that trauma
      is strongly associated with anger reactions. The present study investigated the
      relationship between IED and a number of trauma-related factors, including trauma
      dosage, timing of first trauma, and posttraumatic stress disorder (PTSD).
      Participants were 4844 trauma-exposed and 731 non trauma-exposed adults who took
      part in the National Comorbidity Survey-Replication (NCS-R). Findings indicated
      that IED was associated with greater trauma exposure, PTSD and generalized
      anxiety disorder (GAD) diagnosis, and first exposure to traumatic events in
      childhood. Exploratory analyses investigating the link between IED and age at
      first trauma exposure across trauma types suggested that IED is related to
      childhood exposure to interpersonal traumatic events. These findings are
      discussed in the context of developmental trauma and cycles of violence models.

PMID- 22464048
TI  - Cheating experience: Guiding novices to adopt the gaze strategies of experts
      expedites the learning of technical laparoscopic skills.
AB  - BACKGROUND: Previous research has demonstrated that trainees can be taught (via
      explicit verbal instruction) to adopt the gaze strategies of expert laparoscopic
      surgeons. The current study examined a software template designed to guide
      trainees to adopt expert gaze control strategies passively, without being
      provided with explicit instructions. METHODS: We examined 27 novices (who had no
      laparoscopic training) performing 50 learning trials of a laparoscopic training
      task in either a discovery-learning (DL) group or a gaze-training (GT) group
      while wearing an eye tracker to assess gaze control. The GT group performed
      trials using a surgery-training template (STT); software that is designed to
      guide expert-like gaze strategies by highlighting the key locations on the
      monitor screen. The DL group had a normal, unrestricted view of the scene on the
      monitor screen. Both groups then took part in a nondelayed retention test (to
      assess learning) and a stress test (under social evaluative threat) with a normal
      view of the scene. RESULTS: The STT was successful in guiding the GT group to
      adopt an expert-like gaze strategy (displaying more target-locking fixations).
      Adopting expert gaze strategies led to an improvement in performance for the GT
      group, which outperformed the DL group in both retention and stress tests (faster
      completion time and fewer errors). CONCLUSION: The STT is a practical and cost
      effective training interface that automatically promotes an optimal gaze
      strategy. Trainees who are trained to adopt the efficient target-locking gaze
      strategy of experts gain a performance advantage over trainees left to discover
      their own strategies for task completion.

PMID- 22464049
TI  - Significance of circulating toxin and antitoxin in unimmunized tetanus cases of
      neonates and infants.
AB  - The level of circulating tetanus toxin, antitoxin and their individual influence
      on the outcome of tetanus cases were determined in unimmunized 125 neonatal and
      39 infant cases of tetanus. PHA (passive haemagglutination) test showed 40%
      positive cases for toxin while its absence in the remaining cases indicated of
      either toxin fixation to the central nervous system (CNS) or it got neutralized
      by antitoxin. TN (toxin neutralization) and PHA test carried out in 46 sera
      samples revealed a strong positive correlation (r = 0.9) showing that 35/46 (76%)
      and 38/46 (82.6%) samples were positive for antitoxin, respectively. 25.4% of the
      neonate and infant cases and 34% of the control group had a protective serum
      tetanus antitoxin level. 42.5% of the paired sera from unimmunized mothers and
      their neonates showing nonprotective antitoxin levels suggested that a high level
      of antitoxin is needed for transplacental transfer, although transfer may not
      play a decisive role in the resistance against the disease. The presence of toxin
      or antitoxin in the clinical cases did not affect the outcome of the disease,
      although in neonates, presence of toxin was found to be a bad prognostic sign.
      This study explicitly advocates for the need to improve the vaccination coverage
      strategy.

PMID- 22464050
TI  - Marijuana use trajectories during the post-college transition: health outcomes in
      young adulthood.
AB  - BACKGROUND: Despite the relatively high prevalence of marijuana use among college
      students, little information exists regarding health outcomes associated with
      different use patterns or trajectories. METHODS: Seven annual personal interviews
      (years 1-7) were administered to 1253 individuals, beginning in their first year
      in college. Growth mixture modeling was used to identify trajectories of
      marijuana, alcohol, and tobacco use frequency during years 1-6. Logistic
      regression was used to evaluate the relationship between marijuana use
      trajectories and several year 7 health outcomes, holding constant year 1 health,
      demographics, and alcohol and tobacco use trajectories. RESULTS: Six marijuana
      use trajectories were identified: non-use (71.5% (wt) of students), low-stable
      (10.0% (wt)), late-increase (4.7% (wt)), early-decline (4.3% (wt)), college-peak
      (5.4% (wt)), and chronic (4.2% (wt)). The six marijuana trajectory groups were
      not significantly different on year 1 health-related variables, but differed on
      all ten year 7 health outcomes tested, including functional impairment due to
      injury, illness, or emotional problems; general health rating; psychiatric
      symptoms; health-related quality of life; and service utilization for physical
      and mental health problems. Non-users fared significantly better than most of the
      marijuana-using trajectory groups on every outcome tested. Chronic and late
      increase users had the worst health outcomes. CONCLUSIONS: Marijuana use patterns
      change considerably during college and the post-college period. Marijuana-using
      students appear to be at risk for adverse health outcomes, especially if they
      increase or sustain a frequent pattern of use.

PMID- 22464051
TI  - Red blood cell fatty acids are associated with depression in a case-control study
      of adolescents.
AB  - INTRODUCTION: Epidemiological studies suggest that reduced intakes and/or blood
      levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are
      associated with increased risk for depression in adults, but data on adolescents
      are scarce. The objective of this study was to determine whether red blood cell
      (RBC) levels of EPA+DHA (the omega-3 index) and/or the overall RBC fatty acid
      profile differ between depressed adolescents (cases) and non-depressed
      adolescents (controls). PATIENTS AND METHODS: We measured the RBC fatty acid
      composition of cases admitted to the hospital for depression (n=150) and compared
      it to that of controls (n=161). RESULTS: Cases and controls had similar ages,
      gender proportions, and body mass index (BMI) distributions, but there was a
      significant difference in racial/ethnic composition due to differences in
      recruitment sites. The unadjusted odds ratio for case status was 0.72 (95% CI;
      0.55-0.95) for a 1% absolute increase in the omega-3 index. A multivariable
      logistic regression model was used to determine which fatty acids were useful in
      classifying cases and controls; BMI, age, gender, and race/ethnicity were forced
      into the model. Seven fatty acids were selected (DHA, myristic, stearic, oleic,
      trans linoleic, trans palmitoleic, and alpha-linolenic acids) to optimize the
      model fit to the data. In the adjusted model, the odds ratio was 0.67 (95% CI;
      0.49-0.93) for a 1 SD increase in DHA. Adding the seven fatty acid profile to the
      basic model increased the area under the ROC curve by 12.6% (7.5%-17.6%).
      DISCUSSION AND CONCLUSION: These findings support the hypothesis that adolescent
      depression is associated with a perturbed RBC fatty acid pattern which includes a
      reduced omega-3 index. Intervention studies with EPA and DHA should be conducted
      in this vulnerable population for which few, safe therapeutic options currently
      exist.

PMID- 22464053
TI  - Therapeutic experimentation in the elderly.

PMID- 22464052
TI  - Models of plasma membrane organization can be applied to mitochondrial membranes
      to target human health and disease with polyunsaturated fatty acids.
AB  - Bioactive n-3 polyunsaturated fatty acids (PUFA), abundant in fish oil, have
      potential for treating symptoms associated with inflammatory and metabolic
      disorders; therefore, it is essential to determine their fundamental molecular
      mechanisms. Recently, several labs have demonstrated the n-3 PUFA docosahexaenoic
      acid (DHA) exerts anti-inflammatory effects by targeting the molecular
      organization of plasma membrane microdomains. Here we briefly review the evidence
      that DHA reorganizes the spatial distribution of microdomains in several model
      systems. We then emphasize how models on DHA and plasma membrane microdomains can
      be applied to mitochondrial membranes. We discuss the role of DHA acyl chains in
      regulating mitochondrial lipid-protein clustering, and how these changes alter
      several aspects of mitochondrial function. In particular, we summarize effects of
      DHA on mitochondrial respiration, electron leak, permeability transition, and
      mitochondrial calcium handling. Finally, we conclude by postulating future
      experiments that will augment our understanding of DHA-dependent membrane
      organization in health and disease.

PMID- 22464054
TI  - Enrollment revalidation: pitfalls and tips.

PMID- 22464055
TI  - Stand by me--preventing falls.

PMID- 22464056
TI  - The family caregiver: an untapped resource.

PMID- 22464057
TI  - hTERT gene amplification and clinical significance in pleural effusions of
      patients with lung cancer.
AB  - PATIENTS AND METHODS: Human telomerase reverse transcriptase (hTERT) gene
      amplification was detected in pleural effusions of patients with lung cancer (n =
      69) and in patients with benign lung disease (n = 46) when using a quantitative
      polymerase chain reaction (qPCR) technique. RESULTS: hTERT gene relative copy
      numbers were significantly higher in effusions from patients with malignant,
      adenocarcinoma and small-cell lung cancer than in effusions from patients with
      benign lung disease (P < .01). By using a threshold value of 1.39, hTERT gene
      amplification was significantly more frequent in malignant effusions compared
      with benign effusions and more likely to be positive for malignant effusions,
      compared with cytology (P < .01). The diagnostic performance of qPCR of hTERT
      gene amplification was significantly higher than that of cytology, in terms of
      sensitivity (91.3% vs. 56.5%), negative predictive value (87.8% vs. 60.5%), and
      accuracy (92.2% vs. 73.9%). CONCLUSIONS: Detecting hTERT gene amplification by
      qPCR appears suitable for distinguishing carcinoma cells from reactive
      mesothelial cells in pleural effusions. hTERT gene amplification was more
      sensitive than cytology and may be useful for diagnosing pleural micrometastases.

PMID- 22464058
TI  - [San Antonio Breast Cancer Symposium 2011 (SABCS): what place will remain to the
      axillary dissection?].

PMID- 22464059
TI  - [Hormone replacement therapy: do we have to choose between breast and endometrial
      cancer?].

PMID- 22464060
TI  - The catalytic activity enhancement and biodegradation potential of free laccase
      and novel sol-gel laccase in non-conventional solvents.
AB  - The catalytic activity of free laccase and a novel sol-gel laccase (SOLAC) in
      ionic liquids and organic solvents was demonstrated by using 2,6-dimethoxyphenol
      (2,6-DMP) as a substrate. The enhancement of the catalytic activity of the SOLAC
      was observed and compared to the free laccase in both media. The oxidative
      biodegradation of o-chlorophenol as a model of phenolic environmental pollutants
      in organic media shows that the degradation was observed only when using water
      pre-saturated organic solvents or reverse micelle system. The SOLAC gave higher
      biodegradation rate in either aqueous or organic solvents, in which the optimum
      temperature was observed at 40  degrees C for the reverse micelle system as a
      reaction medium. All results demonstrated the potential use of the SOLAC for
      biodegradation of phenolic environmental pollutants in non-conventional media.

PMID- 22464061
TI  - Enhanced production of glucose and xylose with partial dissolution of corn stover
      in ionic liquid, 1-Ethyl-3-methylimidazolium acetate.
AB  - Partial dissolution of corn stover in ionic liquid (IL) was employed for
      pretreating biomass and achieving enhanced glucose and xylose yield. The xylan
      recovery in solid fraction after IL pretreatment decreased as temperature
      increased. Xylose yield was significantly increased at a relatively low
      temperature (110  degrees C) compared with the high-temperature (over 130 
      degrees C) pretreatment, which resulted in a significant xylan degradation. A
      maximum total sugar yield of 88.0%, with glucose yield of 93.9% and xylose yield
      of 75.9% based on untreated biomass, was obtained at 110  degrees C for 3h
      pretreatment without complete dissolution of biomass. A sugar yield of 78.0% was
      obtained with IL pretreatment at 70  degrees C for 24 h. Synchrotron wide-angle X
      ray diffraction was employed to investigate the crystalline structure of biomass.
      Both cellulose crystallinity and remaining lignin amount were correlated with
      cellulose digestibility.

PMID- 22464062
TI  - Lipase-mediated synthesis of water-soluble plant stanol derivatives in tert
      butanol.
AB  - The effects of solvents with different log P values, and of lipases on the
      synthesis of water-soluble plant stanol derivatives were investigated. Results
      showed that conversion in solvents with log P<0.37 was mainly controlled by the
      hydrophobicity of the solvent and subsequent complete or partial deactivation of
      the enzyme. The solubility of substrate was the leading factor for the conversion
      in solvents with log P>0.37. Lipozyme RM IM and tert-butanol was the most
      suitable biocatalyst and solvent, respectively. The highest yield (>51%) of plant
      stanyl sorbitol succinate was obtained under the selected conditions: 50 MUmol/mL
      plant stanyl hemisuccinate, 1:3 molar ratio of plant stanyl hemisuccinate to d
      sorbitol, 80 mg/mL 3 A molecular sieves and 100mg/mL Lipozyme RM IM in tert
      butanol, 150 r/min and 55  degrees C. Fourier transform infrared spectroscopy,
      mass spectroscopy and nuclear magnetic resonance spectroscopy were adopted to
      determine the structure of product, suggesting that water-soluble plant stanol
      derivatives were successfully synthesized.

PMID- 22464063
TI  - Predictors of physical activity change during adolescence: a 3.5-year follow-up.
AB  - OBJECTIVE: To investigate the predictors of change in physical activity (PA) from
      early to mid adolescence in a cohort of adolescents. DESIGN: Prospective,
      population-based birth cohort study. PA level was evaluated by means of
      questionnaire, and was analysed in continuous form (min/week) and as a trajectory
      (inactive-inactive, inactive-active, active-inactive, active-active) based on the
      cut-off point of 300 min/week. SETTING: Pelotas, a city of 340 000 inhabitants in
      southern Brazil. SUBJECTS: Adolescents (n 4120) followed from 11 to 15 years of
      age. RESULTS: Maternal PA change and more exposure to outdoors were directly
      associated with a positive change in PA level (min/week) for both genders. Higher
      maturation status (among boys) and later menarche were also associated with
      positive PA change in min/week. Predictors to remain inactive were: maternal PA
      change (inverse association), more exposure to outdoors, higher socio-economic
      level, fear of living in the neighbourhood and non-overweight girls. Predictors
      to become inactive were higher socio-economic level among boys and increase in
      screen time among girls. CONCLUSIONS: The study demonstrates that social, family,
      biological, behavioural and environmental factors exert an important role in the
      PA change among youngsters as they move into adolescence. These findings may be
      relevant to the design of policies and intervention programmes aimed at promoting
      PA in teenagers.

PMID- 22464064
TI  - Noninvasive prenatal testing for aneuploidy-ready for prime time?

PMID- 22464065
TI  - The natural history of pelvic vein thrombosis: the natural history of involution?

PMID- 22464066
TI  - Doppler assessment of the fetus with intrauterine growth restriction.
AB  - OBJECTIVE: We sought to provide evidence-based guidelines for utilization of
      Doppler studies for fetuses with intrauterine growth restriction (IUGR). METHODS:
      Relevant documents were identified using PubMed (US National Library of Medicine,
      1983 through 2011) publications, written in English, which describe the
      peripartum outcomes of IUGR according to Doppler assessment of umbilical
      arterial, middle cerebral artery, and ductus venosus. Additionally, the Cochrane
      Library, organizational guidelines, and studies identified through review of the
      above were utilized to identify relevant articles. Consistent with US Preventive
      Task Force suggestions, references were evaluated for quality based on the
      highest level of evidence, and recommendations were graded. RESULTS AND
      RECOMMENDATIONS: Summary of randomized and quasirandomized studies indicates
      that, among high-risk pregnancies with suspected IUGR, the use of umbilical
      arterial Doppler assessment significantly decreases the likelihood of labor
      induction, cesarean delivery, and perinatal deaths (1.2% vs 1.7%; relative risk,
      0.71; 95% confidence interval, 0.52-0.98). Antepartum surveillance with Doppler
      of the umbilical artery should be started when the fetus is viable and IUGR is
      suspected. Although Doppler studies of the ductus venous, middle cerebral artery,
      and other vessels have some prognostic value for IUGR fetuses, currently there is
      a lack of randomized trials showing benefit. Thus, Doppler studies of vessels
      other than the umbilical artery, as part of assessment of fetal well-being in
      pregnancies complicated by IUGR, should be reserved for research protocols.

PMID- 22464068
TI  - The risk of stillbirth and infant death stratified by gestational age in women
      with gestational diabetes.
AB  - OBJECTIVE: We sought to compare the different mortality risks between delivery
      and expectant management in women with gestational diabetes mellitus (GDM). STUDY
      DESIGN: This is a retrospective cohort study that included singleton pregnancies
      of women diagnosed with GDM delivering at 36-42 weeks' gestational age in
      California from 1997 through 2006. A composite mortality rate was developed to
      estimate the risk of expectant management at each gestational age incorporating
      the stillbirth risk during the week of continuing pregnancy plus the infant
      mortality risk at the gestational age 1 week hence. RESULTS: In women with GDM,
      the risk of expectant management is lower than the risk of delivery at 36 weeks
      (17.4 vs 19.3/10,000), but at 39 weeks, the risk of expectant management exceeds
      that of delivery (relative risk, 1.8; 95% confidence interval, 1.2-2.6).
      CONCLUSION: In women with GDM, infant mortality rates at 39 weeks are lower than
      the overall mortality risk of expectant management for 1 week; absolute risks of
      stillbirth and infant death are low.

PMID- 22464070
TI  - Autism risk in small- and large-for-gestational-age infants.
AB  - OBJECTIVE: We sought to determine whether small-for-gestational age (SGA) and
      large-for-gestational age (LGA) birthweights increase autism risk. STUDY DESIGN:
      This was a retrospective cohort analysis comparing children with autism (n =
      20,206) within a birth cohort (n = 5,979,605). Stratification by sex and
      birthweight percentile (SGA, <5th or 5-10th percentile; appropriate size for
      gestational age [GA], >10th to <90th percentile; LGA, either 90-95th or >95th
      percentile) preceded Cochran-Mantel-Haenszel analysis for GA effect, and
      multivariate analysis. RESULTS: Autism risk was increased in preterm SGA (<5th
      percentile) infants 23-31 weeks (adjusted odds ratio [aOR], 1.60; 95% confidence
      interval [CI], 1.09-2.35) and 32-33 weeks (aOR, 1.83; 95% CI, 1.16-2.87), and
      term LGA (>95th percentile) infants 39-41 weeks (aOR, 1.16; 95% CI, 1.08-1.26),
      but was decreased in preterm LGA infants 23-31 weeks (aOR, 0.45; 95% CI, 0.21
      0.95). CONCLUSION: SGA was associated with autism in preterm infants, while LGA
      demonstrated dichotomous risk by GA, with increased risk at term, and decreased
      risk in the premature infants. These findings likely reflect disparate
      pathophysiologies, and should influence prenatal counseling, pediatric autism
      screening, and further autism research.

PMID- 22464071
TI  - Rates of bacteriuria in laboring women with epidural analgesia: continuous vs
      intermittent bladder catheterization.
AB  - OBJECTIVE: The purpose of this study was to compare the rates of bacteriuria in
      laboring women with epidural analgesia with the use of intermittent bladder
      catheterization (IC) vs continuous indwelling Foley catheterization (CIF). STUDY
      DESIGN: We conducted a randomized, nonblinded trial in which 160 laboring women
      received IC or CIF. An initial catheterized urine culture was taken at the time
      of epidural placement. A second catheterized or voided culture was taken at
      discharge. Results were analyzed to compare bacteriuria rates between CIF and IC
      with the use of the Center for Disease Control (CDC) and Infectious Disease
      Society of America (IDSA) definitions. RESULTS: Samples from 146 women were
      analyzed. Randomization, demographics, and labor characteristics were not
      significantly different between groups; 5.48% of the samples met CDC criteria for
      bacteriuria, and 17.8% of the samples met IDSA criteria. In the IC group, 7
      samples (8.9%) met CDC criteria for bacteriuria, and 18 samples (22.8%) met IDSA
      criteria for bacteriuria. In the CIF group, 1 sample (1.5%) met CDC criteria, and
      8 samples (12.1%) met IDSA criteria. There was a significantly higher rate of
      bacteriuria by both criteria in the IC group among all deliveries, all vaginal
      deliveries, and spontaneous vaginal deliveries (P < .05). CONCLUSION: Compared
      with CIF, IC was associated with significantly higher rates of bacteriuria.

PMID- 22464069
TI  - Elective repeat cesarean delivery compared with spontaneous trial of labor after
      a prior cesarean delivery: a propensity score analysis.
AB  - OBJECTIVE: The purpose of this study was to determine outcomes, after the use of
      propensity score techniques, to create balanced groups according to whether a
      woman undergoes elective repeat cesarean delivery (ERCD) or trial of labor (TOL).
      STUDY DESIGN: Women who were eligible for a TOL with 1 previous low transverse
      incision were categorized according to whether they underwent an ERCD or TOL. A
      propensity score technique was used to develop ERCD and TOL groups with
      comparable baseline characteristics. Outcomes were assessed with conditional
      logistic regression. RESULTS: The rates of endometritis, operative injury,
      respiratory distress syndrome, and newborn infant infection were lower and the
      rates of hysterectomy and wound complication were higher in the ERCD group.
      CONCLUSION: Propensity score techniques can be used to generate comparable ERCD
      and TOL groups. Some types of maternal morbidity (such as hysterectomy) are
      higher; other types (such as operative injury) are lower in the ERCD group.
      Although the absolute risk is low, neonatal morbidity appears to be lower in the
      ERCD group.

PMID- 22464072
TI  - Noninvasive prenatal detection and selective analysis of cell-free DNA obtained
      from maternal blood: evaluation for trisomy 21 and trisomy 18.
AB  - OBJECTIVE: We sought to develop a novel biochemical assay and algorithm for the
      prenatal evaluation of risk for fetal trisomy 21 (T21) and trisomy 18 (T18) using
      cell-free DNA obtained from maternal blood. STUDY DESIGN: We assayed cell-free
      DNA from a training set and a blinded validation set of pregnant women,
      comprising 250 disomy, 72 T21, and 16 T18 pregnancies. We used digital analysis
      of selected regions in combination with a novel algorithm, fetal-fraction
      optimized risk of trisomy evaluation (FORTE), to determine trisomy risk for each
      subject. RESULTS: In all, 163/171 subjects in the training set passed quality
      control criteria. Using a Z statistic, 35/35 T21 cases and 7/7 T18 cases had Z
      statistic >3 and 120/121 disomic cases had Z statistic <3. FORTE produced an
      individualized trisomy risk score for each subject, and correctly discriminated
      all T21 and T18 cases from disomic cases. All 167 subjects in the blinded
      validation set passed quality control and FORTE performance matched that observed
      in the training set correctly discriminating 36/36 T21 cases and 8/8 T18 cases
      from 123/123 disomic cases. CONCLUSION: Digital analysis of selected regions and
      FORTE enable accurate, scalable noninvasive fetal aneuploidy detection.

PMID- 22464073
TI  - Chromosome-selective sequencing of maternal plasma cell-free DNA for first
      trimester detection of trisomy 21 and trisomy 18.
AB  - OBJECTIVE: The purpose of this study was to assess the prenatal detection rate of
      trisomy 21 and 18 and the false-positive rate by chromosome-selective sequencing
      of maternal plasma cell-free DNA. STUDY DESIGN: Nested case-control study of cell
      free DNA was examined in plasma that was obtained at 11-13 weeks before chorionic
      villous sampling from 300 euploid pregnancies, 50 pregnancies with trisomy 21,
      and 50 pregnancies with trisomy 18. Laboratory personnel were blinded to fetal
      karyotype. RESULTS: Risk scores for trisomy 21 and 18 were given for 397 of the
      400 samples that were analyzed. In all 50 cases of trisomy 21, the risk score for
      trisomy 21 was >= 99%, and the risk score for trisomy 18 was <= 0.01%. In all 50
      cases of trisomy 18, the risk score for trisomy 21 was <= 0.01%, and the risk
      score for trisomy 18 was >= 99% in 47 cases, 98.8% in 1 case, 88.5% in 1 case,
      and 0.11% in 1 case. In 3 of the 300 euploid pregnancies (1%), no risk score was
      provided, because there was failed amplification and sequencing. In the remaining
      297 cases, the risk score for trisomy 21 was <= 0.01%, and the risk score for
      trisomy 18 was <= 0.01% in 295 cases, 0.04% in 1 case, and 0.23% in 1 case.
      Therefore, the sensitivity for detecting trisomy 21 was 100% (50/50 cases); the
      sensitivity for trisomy 18 was 98% (49/50 cases), and the specificity was 100%
      (297/297 cases). CONCLUSION: In this study, chromosome-selective sequencing of
      cell-free DNA separated all cases of trisomy 21 and 98% of trisomy 18 from
      euploid pregnancies.

PMID- 22464074
TI  - Factors associated with screening for sexually transmitted infections.
AB  - OBJECTIVE: The purpose of this study was to determine predictors of the
      completion of free annual sexually transmitted infection screening among sexually
      active young women of <= 25 years old. STUDY DESIGN: We analyzed survey data from
      2607 sexually active women who were enrolled in the Contraceptive CHOICE Project,
      a prospective cohort study. We evaluated demographic characteristics, sexual risk
      behaviors, relationship characteristics, and contraceptive methods. Receipt of a
      home- or clinic-based test kit within 56 days of the 12-month survey constituted
      a completed screen. A multivariable model to predict screening completion was
      created with the use of Poisson regression with robust error variance. RESULTS:
      Fifty-seven percent of the women completed the screening. Screening completion
      was associated most strongly with a college education or higher (adjusted
      relative risk, 1.2; 95% confidence interval, 1.1-1.3) and home-based testing
      (adjusted relative risk, 1.3; 95% confidence interval, 1.2-1.5). CONCLUSION: Free
      and home-based testing increased screening rates among young women. To meet
      annual testing guidelines, the availability and use of home-based testing kits
      should increase.

PMID- 22464075
TI  - Methicillin-resistant Staphylococcus aureus colonization among women admitted for
      preterm delivery.
AB  - OBJECTIVE: Methicillin-resistant Staphylococcus aureus infection is associated
      with morbidity in the neonatal intensive care unit. The purpose of this study was
      to determine the relationship between preterm maternal methicillin-resistant S
      aureus colonization and subsequent colonization and infection in premature
      neonates. STUDY DESIGN: We conducted a prospective cohort study of 422 women
      admitted for preterm delivery. Methicillin-resistant S aureus cultures were
      collected from mothers and their neonates admitted to neonatal intensive care
      unit. We determined the proportion of women and neonates colonized with
      methicillin-resistant S aureus and examined possible factors associated with
      colonization and infection. RESULTS: Fifteen of 422 (3.6%) women were found to be
      colonized with methicillin-resistant S aureus. Thirteen of 212 (6.1%) neonates
      admitted to neonatal intensive care unit were methicillin-resistant S aureus
      colonized and 3 of 13 (23.1%) developed a methicillin-resistant S aureus
      infection. We identified 1 methicillin-resistant S aureus colonized maternal
      neonatal pair. The infant became methicillin-resistant S aureus positive 30 days
      after admission and did not develop a methicillin-resistant S aureus infection.
      CONCLUSION: These findings suggest that maternal methicillin-resistant S aureus
      colonization is not a significant risk factor for vertical transmission of
      neonatal methicillin-resistant S aureus colonization.

PMID- 22464076
TI  - Inequities in the use of cesarean section deliveries in the world.
AB  - OBJECTIVE: The purpose of this study was to describe the unequal distribution in
      the performance of cesarean section delivery (CS) in the world and the resource
      use implications of such inequity. STUDY DESIGN: We obtained data on the number
      of CSs performed in 137 countries in 2008. The consensus is that countries should
      achieve a 10% rate of CS; therefore, for countries that are below that rate, we
      calculated the cost to achieve a 10% rate. For countries with a CS rate of >15%,
      we calculated the savings that could be made by the achievement of a 15% rate.
      RESULTS: Fifty-four countries had CS rates of <10%, whereas 69 countries showed
      rates of >15%. The cost of the global saving by a reduction of CS rates to 15%
      was estimated to be $2.32 billion (US dollars); the cost to attain a 10% CS rate
      was $432 million (US dollars). CONCLUSION: CSs that are potentially medically
      unjustified appear to command a disproportionate share of global economic
      resources.

PMID- 22464077
TI  - Prospective investigation of second-trimester thrombin activation and preterm
      birth.
AB  - OBJECTIVE: We sought to determine if second-trimester amniotic fluid thrombin
      antithrombin (TAT) complexes concentration correlates with subsequent preterm
      birth. STUDY DESIGN: A cohort of 550 women with singleton nonanomalous
      pregnancies undergoing second-trimester genetic amniocentesis was followed up to
      delivery and analyzed as a nested case-control study. Cases of preterm birth (n =
      52) were compared with 104 term control subjects. Amniotic fluid collected at
      amniocentesis was tested for TAT. RESULTS: TAT concentrations were significantly
      higher in women who delivered preterm (median 115.9 ug/L) than in those who did
      not (median 62.2 ug/L; P < .001). This difference persisted when 31 spontaneous
      preterm births and 21 indicated preterm births were analyzed separately. The odds
      ratios for preterm birth in the highest TAT quartile relative to the lowest
      quartile was 4.98 (95% confidence interval, 1.17-22.01; P = .007). CONCLUSION: We
      found a difference in the pattern of intraamniotic thrombin generation between
      women destined to deliver at term and those who deliver preterm, regardless of
      the type of preterm birth.

PMID- 22464078
TI  - Hospital-based lateral episiotomy and obstetric anal sphincter injury rates: a
      retrospective population-based register study.
AB  - OBJECTIVE: We sought to determine whether an optimal level of lateral episiotomy
      use can be found by assessing the correlation between the hospital-based
      variations in episiotomy use and rates/odds ratios of obstetric anal sphincter
      injuries (OASIS). STUDY DESIGN: This was a retrospective population-based
      register study. The study group, comprising women with spontaneous singleton
      vaginal deliveries, contained all 154,175 primiparous and all 234,236 multiparous
      women. The correlations between lateral episiotomy use and incidence/risk of
      OASIS (n = 1659) were assessed using nonlinear and linear regression modeling.
      RESULTS: The rates of episiotomy were inversely correlated with the risk of OASIS
      among both groups of women. OASIS rates increased from 0.5-1.0% as episiotomy
      rates decreased from 80-40%. CONCLUSION: Restricting lateral episiotomy use may
      result in higher OASIS rates. However, we could not determine the optimal level
      of episiotomy use since individual hospitals deviated substantially from the
      correlation curves.

PMID- 22464079
TI  - Discussion: 'Occupational exposures and spontaneous abortion' by Lawson et al.

PMID- 22464080
TI  - Inflammation and neurological adverse drugs reactions: a case of long lasting
      impaired consciousness after oxatomide administration in a patient with
      gastroenteritis.
AB  - Oxatomide at therapeutic doses generates occasionally drowsiness in children.
      When administered at toxic doses, however oxatomide may induce long lasting
      impaired consciousness. We now report a case of severe long lasting impaired
      consciousness induced by therapeutic doses of oxatomide occurring in a child
      affected by acute gastroenteritis. The clinical symptoms, the pharmacogenetic
      tests of polymorphisms in cytochrome P450 metabolizing enzymes (CYPs) and the
      clinical and laboratory analyses indicate that the enhanced drug sedative effect
      is likely due to an acute, yet mild, inflammatory state of the patient. These
      findings highlight the importance of assessing common, not serious inflammatory
      states when oxatomide is prescribed in paediatric patients.

PMID- 22464081
TI  - Effect of ovarian stimulation and oocyte retrieval on reproductive outcome in
      oocyte donors.
AB  - OBJECTIVE: To assess whether there is an increased risk of infertility in women
      that have previously undergone ovarian stimulation and oocyte retrieval for
      oocyte donation. DESIGN: Cross-sectional survey. SETTING: Tertiary referral
      center. PATIENT(S): A total of 194 past oocyte donors. INTERVENTION(S): Telephone
      questionnaire. MAIN OUTCOME MEASURE(S): Incidence of infertility after oocyte
      donation. RESULT(S): Of the women who indicated having pursued conception after
      oocyte donation, 95% (57/60) became pregnant unassisted. Before oocyte donation,
      41 women in this cohort had already been trying to conceive, of which 38 had
      delivered a child and 3 (7.3%) had needed infertility treatment. CONCLUSION(S):
      The data suggest that oocyte donation does not affect short-term reproductive
      health.

PMID- 22464082
TI  - Association between the location of transposed ovary and ovarian function in
      patients with uterine cervical cancer treated with (postoperative or primary)
      pelvic radiotherapy.
AB  - OBJECTIVE: To evaluate the effectiveness of ovarian transposition procedures in
      preserving ovarian function in relation to the location of the transposed ovaries
      in patients who underwent surgery with or without pelvic radiotherapy. DESIGN:
      Retrospective. SETTING: Uterine cancer center. PATIENT(S): A total of 53 patients
      with cervical cancer who underwent ovarian transposition between November 2002
      and November 2010. INTERVENTION(S): Ovarian transposition to the paracolic
      gutters with or without radical hysterectomy and lymph node dissection. MAIN
      OUTCOME MEASURE(S): Preservation of ovarian function, which was assessed by
      patient's symptoms and serum FSH level. RESULT(S): Lateral ovarian transposition
      was performed in 53 patients. Based on receiver operator characteristic curve
      analysis, optimum cutoff value of location more than 1.5 cm above the iliac crest
      was significantly associated with preservation of ovarian function after
      treatment (area under receiver operator characteristic curve: 0.757, 95%
      confidence interval [CI]: 0.572-0.943). In univariate analysis, higher location
      of transposed ovary more than 1.5 cm from the iliac crest was the only
      independent factor for intact ovarian function (odds ratio 9.91, 95% CI: 1.75
      56.3). Multivariate analysis confirmed that the location of transposed ovary
      (odds ratio 11.72, 95% CI 1.64-83.39) was the most important factor for intact
      ovarian function. CONCLUSION(S): Location of transposed ovary higher than 1.5 cm
      above the iliac crest is recommended to avoid ovarian failure after lateral
      ovarian transposition after primary or adjuvant pelvic radiotherapy in cervical
      cancer.

PMID- 22464083
TI  - Perinatal and neonatal outcomes of 494 babies delivered from 972 vitrified embryo
      transfers.
AB  - OBJECTIVE: To evaluate the safety of vitrification of embryos by comparing the
      perinatal outcome of vitrified day 3 ETs with fresh cleavage-stage ETs. DESIGN:
      Retrospective analysis. SETTING: Assisted reproduction center. PATIENT(S): A
      total of 806 women with 494 infants delivered were included. INTERVENTION(S):
      Supernumerary embryos and embryos of patients at risk of ovarian hyperstimulation
      syndrome were vitrified using a Cryotop carrier in an open system and were
      transferred after warming. MAIN OUTCOME MEASURE(S): Implantation and pregnancy
      rates, obstetric outcomes, neonatal outcomes, and congenital birth defects.
      RESULT(S): A total of 2,543 vitrified embryos were warmed, and 2,375 survived and
      were transferred. The implantation, pregnancy, miscarriage, and live birth rates
      were 26.91%, 47.22%, 6.07%, and 38.58%, respectively. In singletons, the mean
      birth weight was 3,337.44 g, and the mean Apgar scores were 8.91, 9.85, and 9.89
      at 1, 5, and 10 minutes, respectively. In multiple gestations, the mean birth
      weight was 2,556.45 g, and the mean Apgar scores were 8.90, 9.34, and 9.47 at 1,
      5, and 10 minutes, respectively. Only seven congenital malformations were
      observed among the 494 babies. Compared with fresh cleavage-stage ETs, the mean
      birth weight in the vitrified group was higher in both singleton and multiple
      gestations. All the other results were similar between the two groups.
      CONCLUSION(S): Compared with fresh ETs, vitrified day 3 ET shows no significant
      differences in obstetrical and neonatal outcomes. The study suggests that
      vitrification with Cryotop is an effective and safe method for the
      cryopreservation of human cleavage-stage (day 3) embryos.

PMID- 22464085
TI  - Aromatase expression in abdominal omental/visceral and subcutaneous fat depots: a
      comparison of pregnant and obese women.
AB  - OBJECTIVE: To investigate total and promoter expression of aromatase in
      subcutaneous and omental (visceral) fat and compare this expression in pregnant
      and obese women. DESIGN: Cross-sectional study. SETTING: Academic hospital.
      PATIENT(S): Six women undergoing elective cesarean section and three women
      undergoing bariatric surgery. INTERVENTION(S): Subcutaneous and omental fat
      obtained during surgery. MAIN OUTCOME MEASURE(S): Total aromatase and promoter
      expression was measured by polymerase chain reaction and protein levels by
      Western blotting. RESULT(S): Total aromatase expression was significantly higher
      in omental compared with subcutaneous fat from pregnant women; this pattern was
      reversed in obese women. Aromatase messenger RNA in omentum was significantly
      higher in pregnancy than obesity, and this was linked to an up-regulation of
      promoter II (PII). Promoter 1.4 (P1.4) expression was lower than PII, and there
      was no difference in P1.4 expression between the two fat depots from pregnant
      subjects. In obese women both P1.4 and PII were up-regulated in subcutaneous
      compared with omental depots, with P1.4 expression greater than that of PII.
      Aromatase protein levels were extremely low in fat depots of pregnant women and
      undetectable in obese women. CONCLUSION(S): There are differences between total
      aromatase and promoter expression in subcutaneous and omental fat from pregnant
      compared with obese women. These differences support the evidence that the fat
      depots are derived from different cell lineages and that the promoter-derived
      aromatase translation varies according to physiologic/pathophysiologic status.

PMID- 22464084
TI  - Suppression of spermatogenesis before grafting increases survival and supports
      resurgence of spermatogenesis in adult mouse testis.
AB  - OBJECTIVE: To test whether absence of complete spermatogenesis in mature
      testicular tissue before grafting will increase graft survival. DESIGN:
      Prospective experimental study. SETTING: Laboratory. ANIMAL(S): Donor testes were
      obtained from adult untreated mice, adult mice rendered cryptorchid, and adult
      mice treated with a GnRH antagonist (acyline). INTERVENTION(S): Donor testes were
      ectopically grafted to nude mice and recovered at three time points. MAIN OUTCOME
      MEASURE(S): Most advanced germ cell type and presence of spermatogonia were
      assessed. Donor testes and grafts were analyzed by histology and by
      immunocytochemistry for ubiquitin C-terminal hydrolase-L1 to mark germ cells.
      RESULT(S): Suppression of spermatogenesis by inducing cryptorchidism or acyline
      treatment resulted in improved survival of grafted tissue compared with controls
      and recovery of complete spermatogenesis, whereas control testis grafts mostly
      degenerated and did not restore complete spermatogenesis. CONCLUSION(S): These
      results indicate that complete spermatogenesis at the time of grafting has a
      negative effect on graft survival. Grafting of adult testis tissue from donors
      with suppressed spermatogenesis leads to spermatogenic recovery and may provide a
      tool to study and preserve fertility and for conservation of genetic resources in
      individuals that lack complete germ cell differentiation.

PMID- 22464086
TI  - Repeated implantation failure: clinical approach.
AB  - Successful embryo implantation depends on a well-functioning endometrium as well
      as a normal healthy embryo. This process might be hampered if either of these
      variables is defective. Repeated implantation failure (RIF) is diagnosed when
      good-quality embryos repeatedly fail to implant after transfer in several IVF
      treatment cycles. The causes of RIF originate with either the mother or the
      embryo. The authors discuss factors that are associated with RIF and address
      various treatment options.

PMID- 22464087
TI  - Efficacy and safety of human chorionic gonadotropin for follicular phase
      stimulation in assisted reproduction: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the efficacy and safety of hCG to induce follicular
      stimulation. DESIGN: Systematic literature searches of PubMed, EMBASE, CENTRAL,
      and SciSearch databases. Randomized controlled trials (RCTs) using hCG in early
      or late follicular phases were included. SETTING: Three reproductive medicine
      services of gynecology in Spain and two universities. PATIENT(S): A total of
      1,068 women treated in 11 RCTs were included. INTERVENTION(S): Use of hCG versus
      other hormone treatments, no administration, or placebo during the period of
      follicular stimulation. MAIN OUTCOME MEASURE(S): Live birth, clinical pregnancy,
      mature oocytes, miscarriage, ovarian hyperstimulation syndrome (OHSS), and FSH
      doses. RESULT(S): No differences in live birth, miscarriage, and OHSS rates
      between hCG (given at either the early or late follicular phases) and different
      control regimens were found. Pooled analysis for clinical pregnancy showed
      significant differences in favor of hCG at the late follicular phase. The doses
      of FSH were lower in women treated with hCG at either the early or late
      follicular phase than in those treated with FSH alone. CONCLUSION(S): The use of
      hCG in the early and late follicular phase in controlled ovarian stimulation has
      the advantage of decreasing the doses of FSH.

PMID- 22464088
TI  - Diaphragmatic breathing training program improves abdominal motion during natural
      breathing in patients with chronic obstructive pulmonary disease: a randomized
      controlled trial.
AB  - OBJECTIVE: To investigate the effects of a diaphragmatic breathing training
      program (DBTP) on thoracoabdominal motion and functional capacity in patients
      with chronic obstructive pulmonary disease. DESIGN: A prospective, randomized
      controlled trial. SETTING: Academic medical center. PARTICIPANTS: Subjects (N=30;
      forced expiratory volume in 1s, 42%+/-13% predicted) were randomly allocated to
      either a training group (TG) or a control group (CG). INTERVENTIONS: Subjects in
      the TG completed a 4-week supervised DBTP (3 individualized weekly sessions),
      while those in the CG received their usual care. MAIN OUTCOME MEASURES:
      Effectiveness was assessed by amplitude of the rib cage to abdominal motion ratio
      (RC/ABD ratio) (primary outcome) and diaphragmatic mobility (secondary outcome).
      The RC/ABD ratio was measured using respiratory inductive plethysmography during
      voluntary diaphragmatic breathing and natural breathing. Diaphragmatic mobility
      was measured by ultrasonography. A 6-minute walk test and health-related quality
      of life were also evaluated. RESULTS: Immediately after the 4-week DBTP, the TG
      showed a greater abdominal motion during natural breathing quantified by a
      reduction in the RC/ABD ratio when compared with the CG (F=8.66; P<.001).
      Abdominal motion during voluntary diaphragmatic breathing after the intervention
      was also greater in the TG than in the CG (F=4.11; P<.05). The TG showed greater
      diaphragmatic mobility after the 4-week DBTP than did the CG (F=15.08; P<.001).
      An improvement in the 6-minute walk test and in health-related quality of life
      was also observed in the TG. CONCLUSIONS: DBTP for patients with chronic
      obstructive pulmonary disease induced increased diaphragm participation during
      natural breathing, resulting in an improvement in functional capacity.

PMID- 22464089
TI  - A randomized controlled study to evaluate the efficacy of noninvasive limb cover
      for chronic phantom limb pain among veteran amputees.
AB  - OBJECTIVE: To assess the efficacy of a noninvasive limb cover for treating
      chronic phantom limb pain (PLP). DESIGN: Randomized, double-blind, placebo
      controlled trial. SETTING: Outpatient clinic. PARTICIPANTS: We randomly assigned
      57 subjects to 2 groups: true noninvasive limb cover (n=30) and sham noninvasive
      limb cover (n=27). Inclusion criteria included age of 18 years or greater, upper
      or lower extremity amputation with healed residual limb, and 3 or more episodes
      of PLP during the previous 6 weeks. INTERVENTIONS: Subjects received 2 true or
      sham noninvasive limb covers to be worn over the prosthesis and residual limbs 24
      hours a day for 12 weeks. MAIN OUTCOME MEASURES: Primary outcome measure was the
      numerical pain rating scale of PLP level (0-10). Secondary outcomes included
      overall pain level (0-10), PLP frequency per week, and the Veterans RAND 12-Item
      Health Survey (VR-12). We collected data at baseline and at 6- and 12-week follow
      up visits. RESULTS: Demographic and clinical characteristics were not
      significantly different between groups. The true noninvasive limb cover group
      reported nonsignificant reductions in PLP from 5.9+/-1.9 at baseline to 3.9+/-1.7
      at the 12-week follow-up. The sham noninvasive limb cover group also had
      nonsignificant reducations in PLP from 6.5+/-1.8 to 4.2+/-2.3. PLP did not differ
      significantly between the 2 groups at 6 weeks (mean difference, 0.8; 95%
      confidence interval [CI], -1.4 to 3) or at 12 weeks (mean difference, 0.2; 95%
      CI, -1.9 to 2.3). Similarly, overall pain level, PLP episodes per week, and VR-12
      physical and mental health component scores did not differ between the 2 groups
      at 6 and 12 weeks. CONCLUSIONS: A true noninvasive limb cover did not
      significantly decrease PLP levels or the frequency of PLP episodes per week,
      overall bodily pain levels, or VR-12 physical and mental health component scores
      compared with a sham noninvasive limb cover in our veteran amputee sample.

PMID- 22464090
TI  - Poor agreement on health-related quality of life between children with congenital
      hand differences and their parents.
AB  - OBJECTIVES: To determine agreement between children with congenital hand
      differences (CHDs) and their parents on health-related quality of life (HRQOL)
      and to explore whether characteristic variables were associated with this
      agreement on different domains of HRQOL. DESIGN: Survey. SETTING: University
      hospital, outpatient clinic. PARTICIPANTS: Children with CHD (age range, 10-14 y;
      N=106). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Agreement on HRQOL
      was determined by comparing child self-reports and parent proxy-reports of the
      Pediatric Quality of Life Inventory 4.0 generic core scales, in Dutch. Agreement
      was examined both at group level and individual level. RESULTS: On a group level,
      children scored the same as their parents on a scale of 0 to 100 (physical
      health, 89.1+/-14.1 vs 88.0+/-15.6; psychosocial health, 80.6+/-13.4 vs 79.0+/
      14.5; and total HRQOL, 83.5+/-12.3 vs 82.0+/-13.6). On an individual level,
      however, scoring was subject to high variation, with children reporting both
      higher and lower scores than their parent proxy. There were no major determinants
      for agreement; we only found that agreement was higher on emotional functioning
      in children with more affected fingers and on social functioning in bilaterally
      involved children. CONCLUSIONS: In terms of mean group scores, 10- to 14-year-old
      children with CHD agree with their parents or proxy on the child's HRQOL.
      However, on an individual level, they disagree; on some subdomains limits of
      agreement are as large as 30 points on the 0 to 100 scale. Therefore, care should
      be taken in cases where children are unable to complete the questionnaire in
      choosing the parents' score as a representative substitute for the child's score.

PMID- 22464091
TI  - Recurrence of radicular pain or back pain after nonsurgical treatment of
      symptomatic lumbar disk herniation.
AB  - OBJECTIVES: To determine recurrence rates of lower-extremity radicular pain after
      nonsurgical treatment of acute symptomatic lumbar disk herniation (LDH), and to
      identify predictors of recurrence. DESIGN: Prospective inception cohort. SETTING:
      Outpatient spine clinic. PARTICIPANTS: Patients (N=79) reporting resolution of
      radicular pain after magnetic resonance imaging confirmation of LDH.
      INTERVENTIONS: Individualized nonsurgical treatment tailored to the patient. All
      patients received education, but other treatments varied depending on the
      individual. MAIN OUTCOME MEASURES: Resolution of radicular pain was defined as a
      pain-free period of >=1 month. Patients who reported resolution of radicular pain
      within 1 year after seeking care for acute LDH were asked whether pain had
      recurred at 1 year after seeking care and were also reassessed 1 year after the
      time of resolution of radicular pain and 2 years after seeking care. Patients
      reported on recurrence and the date of recurrence, if any. We evaluated the 1
      year incidence of recurrence, using Kaplan-Meier survival plots. We examined
      predictors of recurrence using bivariate and multivariate Cox proportional
      hazards models. We examined the secondary outcome of back pain recurrence using
      identical methods. RESULTS: Twenty-five percent (95% confidence interval [CI], 15
      35) of individuals with resolution of radicular pain for at least 1 month
      reported subsequent recurrence of pain within 1 year after resolution. The only
      factor independently associated with radicular pain recurrence was the number of
      months prior to resolution of pain (hazard ratio per month=1.24; 95% CI, 1.13
      1.37; P<.001). The 1-year incidence of back pain recurrence was 43% (95% CI, 30
      56), and older age decreased the hazard of recurrence. CONCLUSIONS: Recurrence of
      radicular pain is relatively common after nonsurgical treatment of LDH and is
      predicted by longer time to initial resolution of pain.

PMID- 22464092
TI  - Advanced upper limb prosthetic devices: implications for upper limb prosthetic
      rehabilitation.
AB  - The number of catastrophic injuries caused by improvised explosive devices in the
      Afghanistan and Iraq Wars has increased public, legislative, and research
      attention to upper limb amputation. The Department of Veterans Affairs (VA) has
      partnered with the Defense Advanced Research Projects Agency and DEKA Integrated
      Solutions to optimize the function of an advanced prosthetic arm system that will
      enable greater independence and function. In this special communication, we
      examine current practices in prosthetic rehabilitation including trends in
      adoption and use of prosthetic devices, financial considerations, and the role of
      rehabilitation team members in light of our experiences with a prototype advanced
      upper limb prosthesis during a VA study to optimize the device. We discuss key
      challenges in the adoption of advanced prosthetic technology and make
      recommendations for service provision and use of advanced upper limb prosthetics.
      Rates of prosthetic rejection are high among upper limb amputees. However, these
      rates may be reduced with sufficient training by a highly specialized,
      multidisciplinary team of clinicians, and a focus on patient education and
      empowerment throughout the rehabilitation process. There are significant
      challenges emerging that are unique to implementing the use of advanced upper
      limb prosthetic technology, and a lack of evidence to establish clinical
      guidelines regarding prosthetic prescription and treatment. Finally, we make
      recommendations for future research to aid in the identification of best
      practices and development of policy decisions regarding insurance coverage of
      prosthetic rehabilitation.

PMID- 22464093
TI  - Growth velocity in infancy influences resting energy expenditure in 12-14 year
      old obese adolescents.
AB  - BACKGROUND & AIMS: : To determine if rapid growth between 0 and 2 years of life
      influences body composition and resting energy expenditure (REE) measured at 12
      14 years in a population of obese children. METHODS: REE and body composition
      were measured in 107 obese children aged 12-14 years in whom weight at birth and
      2 years was recorded. RESULTS: 46 obese children had a rapid growth between birth
      and 2 years (>0.67 SD). Rapid weight gain was positively correlated with weight
      and height at 12-14 years but not with body mass index (BMI). Fat mass (FM) to
      fat free mass (FFM) ratio was not significantly different at 12-14 years in
      children with rapid or normal growth velocity. REE in 12-14 year-old children
      with rapid growth (1765+/-222kcal/24h) was significantly higher than children
      with normal growth velocity (1586+/-216kcal/24h) (P<0.001). REE adjusted for FFM
      was similar in the two groups. CONCLUSIONS: Rapid weight gain between 0 and 2
      years of life is associated with higher weight, height, FFM, FM and REE in 12-14
      year-old obese children despite identical BMI. These data demonstrate that growth
      velocity affects later body composition and REE in obese adolescents but
      relationship between REE and FFM is preserved.

PMID- 22464095
TI  - Limb apraxia in multiple sclerosis: prevalence and impact on manual dexterity and
      activities of daily living.
AB  - OBJECTIVE: To evaluate the prevalence and impact of limb apraxia on manual
      dexterity and activities of daily living (ADLs) in patients with multiple
      sclerosis (MS). DESIGN: Survey. SETTING: University hospital. PARTICIPANTS:
      Consecutive patients (N=76) with clinically isolated syndrome, relapsing
      remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis
      (SPMS) or primary progressive multiple sclerosis (PPMS), Expanded Disability
      Status Scale (EDSS) score from 0 to 6.5, and aged from 18 to 70 years were
      included. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Apraxia was
      assessed by the apraxia screen of TULIA (AST). The relationship of apraxia with
      ADLs and manual dexterity was evaluated using a dexterity questionnaire and the
      coin rotation task, respectively. RESULTS: Overall, limb apraxia was found in
      26.3% of patients (mean AST score +/- SD, 7.3+/-1.3; cutoff <9). Apraxia was
      significantly correlated with higher EDSS scores, longer disease duration, and
      higher age with the EDSS being predictive. Furthermore, patients with SPMS and
      PPMS were more apraxic than patients with RRMS. Finally, limb apraxia was
      significantly associated with impaired ADLs and manual dexterity. CONCLUSIONS:
      Limb apraxia is a frequent and clinically significant symptom contributing to
      disability in MS. It should therefore be evaluated and possibly treated,
      particularly in patients with MS reporting manual difficulties in everyday life.

PMID- 22464094
TI  - Rollator use does not consistently change the metabolic cost of walking in people
      with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To (1) evaluate whether the use of a rollator changed metabolic cost
      during a controlled walking task, and (2) explore relationships between the
      difference in dyspnea and metabolic cost associated with rollator use. DESIGN:
      Single-group interventional study in which patients completed 2 corridor walks: 1
      without and 1 with a rollator, at the same individualized constant speed.
      SETTING: Rehabilitation hospital. PARTICIPANTS: Patients with chronic obstructive
      pulmonary disease (N=15; 10 men; median age [interquartile range; IQR]=69 [12]y;
      forced expiratory volume in 1 second=42 [20]% predicted). INTERVENTION: Rollator
      use. MAIN OUTCOME MEASURES: Oxygen uptake, converted to metabolic equivalent
      units (METs), and minute ventilation were measured throughout both tasks using a
      portable gas analysis system; dyspnea and arterial oxygen saturation (SpO(2))
      were collected on completion. RESULTS: Median [IQR] walk speed [IQR] was 48
      (10)m/min. Walking with a rollator, compared with walking without, reduced
      dyspnea (median [IQR]=1.0 [1.5] vs 2.0 [2.0]; P=.01) without changing energy
      expenditure (median [IQR]=2.8 [1.2] vs 3.2 [0.9] METs; P=.65), minute ventilation
      (median [IQR]=30.3 [9.6] vs 27.7 [9.9]L/min; P=.50), or SpO(2) (median [IQR]=92
      [8]% vs 94 [10]%; P=.41). The association between the reduction in dyspnea and
      any difference in energy expenditure related to rollator use was of borderline
      significance (r(s)=.50; P=.06). Six of the 8 participants who experienced a
      reduction in dyspnea also demonstrated a reduction in the metabolic cost of
      walking. CONCLUSIONS: The mechanism responsible for the amelioration in dyspnea
      during rollator-assisted walking is multifactorial. A reduction in the metabolic
      cost of walking may play a part in some, but not all, patients.

PMID- 22464096
TI  - The expression of interleukin-12 is increased by MAP kinase phosphatase-1 through
      a mechanism related to interferon regulatory factor 1.
AB  - Mitogen-activated protein kinase phosphatase-1 (MKP-1) is a nuclear
      tyrosine/threonine phosphatase that inhibits p38 mitogen-activated protein kinase
      (MAPK) activity. We and others have shown that MKP-1 deficiency leads to
      excessive activation of innate immunity and inflammatory gene expression.
      Surprisingly, the present study shows that MKP-1 is a positive regulator of IL-12
      expression in macrophages suggesting a stimulatory effect on Th1 type immune
      response. In the present study, we found that LPS-induced expression of IL-12p40
      was lower in primary mouse peritoneal macrophages (PMs) and bone marrow-derived
      macrophages from MKP-1 deficient mice than in cells from wild-type mice whereas
      TNF expression was enhanced as expected. Correspondingly, the inhibition of p38
      MAPK by pharmacologic inhibitors BIRB 796 and SB 202190 enhanced LPS-induced IL
      12p40 production. Silencing of interferon regulatory factor 1 (IRF1) by siRNA
      inhibited the expression of IL-12p40 in J774 macrophages, showing that IRF1 is an
      important factor regulating IL-12p40 expression. BIRB 796 enhanced LPS-induced
      expression of IRF1 in J774 macrophages and in PMs from wild-type mice, and IRF1
      expression was reduced in PMs from MKP-1 deficient mice. In conclusions, our
      results show that MKP-1 increases and p38 MAPK decreases the expression of IL-12
      by enhancing the expression of IRF1. MKP-1, through regulation of IRF1 and IL-12,
      therefore may be an important factor supporting the development of Th1 type of
      immune response and anti-microbial defense.

PMID- 22464097
TI  - Expression of essential B cell development genes in horses with common variable
      immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous disorder of B cell
      differentiation or function with inadequate antibody production. Our laboratory
      studies a natural form of CVID in horses characterized by late-onset B cell
      lymphopenia due to impaired B cell production in the bone marrow. This study was
      undertaken to assess the status of B cell differentiation in the bone marrow of
      CVID-affected horses by measuring the expression of genes essential for early B
      cell commitment and development. Standard RT-PCR revealed that most of the
      transcription factors and key signaling molecules that directly regulate B cell
      differentiation in the bone marrow and precede PAX5 are expressed in the affected
      horses. Yet, the expression of PAX5 and relevant target genes was variable.
      Quantitative RT-PCR analysis confirmed that the mRNA expression of E2A, PAX5,
      CD19, and IGHD was significantly reduced in equine CVID patients when compared to
      healthy horses (p<0.05). In addition, the PAX5/EBF1 and PAX5/B220 ratios were
      significantly reduced in CVID patients (p<0.01). Immunohistochemical analysis
      confirmed the absence of PAX5-BSAP expression in the bone marrow of affected
      horses. Our data suggest that B cell development seems to be impaired at the
      transition between pre-pro-B cells and pro-B cells in equine CVID patients.

PMID- 22464098
TI  - Intradermal immunization with outer membrane protein 25 protects Balb/c mice from
      virulent B. abortus 544.
AB  - Brucella abortus is a causative agent of brucellosis, a zoonosis affecting the
      endemic areas, which infects domestic animals as well as humans, thus, posing a
      potential bioterror threat. Outer membrane protein 25 is conserved among the
      Brucella species. Omp25 mutant strain of Brucella is shown to be attenuated in
      mice emphasizing on the role of Omp25 in Brucella virulence. Moreover, Omp25 has
      been shown to inhibit TNF-alpha production in human macrophages, thereby,
      abrogating cell mediated immunity. In this study, we evaluated the immunogenic
      potential of recombinant Omp25 and its protective efficacy against virulent B.
      abortus challenge in Balb/c mice. Recombinant Omp25 was administered via two
      routes of immunization: intraperitoneal and intradermal. Dosage reduction was
      observed with intradermal immunization when compared with intraperitoneal
      immunization. A higher IgG1:IgG2b ratio suggested a strong Th2 bias of immune
      response in both the routes of immunization. In vitro stimulation of splenocytes
      from immunized mice resulted in high level of IL-4 along with increasing levels
      of IL-12 and IFN-gamma indicating a mixed Th1 and Th2 type of immune response.
      Immunized mice were challenged with virulent B. abortus and splenic colonization
      of B. abortus reduced significantly in intradermally immunized mice. Intradermal
      immunization gave protection comparable to that of B. abortus S-19 strain.
      Cytokine levels in spleen homogenate after challenge revealed a cell mediated
      immune response with elevated levels of IL-12 and IFN-gamma but no detectable
      amount of IL-4. This can be a possible reason behind the protection observed in
      mice after rOmp25 immunization. Thus, our study proposes recombinant Omp25 to be
      a potential subunit vaccine candidate against brucellosis.

PMID- 22464099
TI  - The role of goal-directed behavior in intention attribution in children.
AB  - In this study, we addressed the question of the nature of the information needed
      by 13-month-old infants to understand another agent's intentions. In two
      experiments, an experimenter was either unable or unwilling to give a toy to an
      infant. Importantly, an implement (a gutter in which the toy could roll down
      toward the infant) was used to make the experimenter's behavior as similar as
      possible in the two conditions. When the experimenter remained still in both
      conditions, infants did not behave differently according to the experimenter's
      intentions, suggesting that they did not infer them. By contrast, in a second
      experiment, where the experimenter performed an action directed toward the gutter
      in both conditions, the infants looked away from the experimental setting more
      often and longer in the unwilling condition than in the unable condition. They
      also looked more toward the experimenter in the unable condition than in the
      unwilling condition. Therefore, we conclude that an agent's intentional attitude
      can already be inferred by a 13-month-old provided that this intention is
      concretely shown through a goal-directed action.

PMID- 22464100
TI  - Ethical review of research protocols: experience of a research ethics committee.
AB  - INTRODUCTION AND OBJECTIVES: Since the passing of the Law on Biomedical Research
      it has been the task of research ethics committees to assess the methodological,
      ethical and legal aspects of all research carried out on humans or human
      biological samples. The aim of the study is to analyze the experience of the
      Research Ethics Committee for the Carlos III Health Institute in the ethical
      assessment of research proposals involving human subjects. METHODS: A descriptive
      study of the observations made on research projects registered between June 1,
      2009 and June 30, 2010. RESULTS: About two thirds of the projects evaluated in
      this period needed some type of amendment. Most of the comments were aimed at
      improving informed consent and procedures to ensure confidentiality (153
      observations, 57.6%). Fifty (18.9%) observations related to the principles of
      beneficence and nonmaleficence. The remaining observations involved incomplete or
      incorrect documentation, or requests for additional information. CONCLUSIONS: The
      largest number of observations related to the autonomy of research participants.
      It is important for researchers to be aware of the principle of autonomy in their
      interaction with study participants. Research ethics committees should therefore
      promote greater understanding of ethical issues on biomedical research.

PMID- 22464101
TI  - Conflict of interest policies and disclosure requirements among European Society
      of Cardiology National Cardiovascular Journals.
AB  - Disclosure of potential conflicts of interest is used by biomedical journals to
      guarantee credibility and transparency of the scientific process. Conflict of
      interest disclosure, however, is not systematically nor consistently dealt with
      by journals. Recent joint editorial efforts paved the way towards the
      implementation of uniform vehicles for conflicts of interest disclosure. This
      paper provides a comprehensive editorial perspective on classical conflict of
      interest-related issues. New insights into current conflicts of interest policies
      and practices among European Society of Cardiology national cardiovascular
      journals, as derived from a cross-sectional survey using a standardised
      questionnaire, are discussed.

PMID- 22464102
TI  - Role of cardiac scintigraphy with 99mTc-DPD in the differentiation of cardiac
      amyloidosis subtype.
AB  - INTRODUCTION AND OBJECTIVES: We investigated the diagnostic accuracy of (99m)Tc
      3,3-diphosphono-1,2 propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy in
      differentiating between monoclonal immunoglobulin light chain and transthyretin
      related cardiac amyloidosis. METHODS: Nineteen patients with documented cardiac
      amyloidosis were included: 8 with transthyretin-related amyloidosis (group A) and
      11 with light chain amyloidosis (group B). All the patients underwent
      scintigraphy with (99m)Tc-DPD and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP).
      RESULTS: On visual scoring, cardiac (99m)Tc-DPD uptake could be characterized as
      moderate to severe (scores of 2-3), with ventricular or biventricular
      distribution, in all group A patients (transthyretin-related cardiac
      amyloidosis), and was absent or mild (scores of 0-1) and diffusely distributed in
      all group B patients (monoclonal immunoglobulin light chain cardiac amyloidosis).
      (99m)Tc-DPD uptake was also absent (score of 0) among unaffected controls and in
      2 unaffected relatives of patients with hereditary transthyretin-related
      amyloidosis who harbor a mutation in the TTR gene. With (99m)Tc-MDP, all the
      patients had a myocardial uptake score of 0-1. In our series, selective
      myocardial uptake of (99m)Tc-DPD provided 100% accuracy (95% confidence interval,
      97.37%-100%) for the differentiation between transthyretin-related and monoclonal
      immunoglobulin light chain cardiac amyloidosis. CONCLUSIONS: We conclude that
      (99m)Tc-DPD scintigraphy is a useful test for the differential diagnosis of
      transthyretin vs monoclonal immunoglobulin light chain etiology in patients with
      cardiac amyloidosis.

PMID- 22464104
TI  - Anticoagulation therapy in patients with heart failure due to systolic
      dysfunction and sinus rhythm: analysis of REDINSCOR registry.
AB  - INTRODUCTION AND OBJECTIVES: In patients with heart failure, left ventricular
      ejection fraction <=35% and sinus rhythm without conditions such as atrial
      fibrillation, thrombus or history of thromboembolic events, the use of
      anticoagulation is controversial. Our objective was to evaluate the
      anticoagulation strategy in these patients, variables associated with its use,
      and its effects on various cardiovascular events. METHODS: Of the patients
      included in the REDINSCOR registry with left ventricular ejection fraction <=35%
      and sinus rhythm without other anticoagulation indications (including patients
      with heart failure from 19 Spanish centres), we compared those who received this
      treatment with the remaining patients. RESULTS: Between 2007 and 2010, 2263
      patients were included, of whom 902 had left ventricular ejection fraction <=35%
      and sinus rhythm. Of these, 237 (26%) were receiving anticoagulation therapy.
      Variables associated with this treatment were a lower left ventricular ejection
      fraction, ischemic etiology, advanced functional class, wider QRS, larger left
      atrial diameter, and hospitalization. After 21(11-32) months of median follow-up,
      there were no significant differences in total mortality (14% versus 12.5%) or
      stroke (0.8% versus 0.9%). A propensity score adjusted multivariate analysis
      showed a reduction in a combined end-point including cardiac death, heart
      transplantation, coronary revascularization, and cardiovascular hospitalization
      (hazard ratio: 0.74; 95% confidence interval, 0.56-0.97; P=.03) in patients
      receiving anticoagulation therapy. No information regarding bleeding was
      collected in the follow-up. CONCLUSIONS: In a large and contemporary series of
      patients with heart failure, left ventricular ejection fraction <=35% and sinus
      rhythm, 26% received anticoagulation therapy. This was not associated with lower
      mortality or stroke incidence, although there was a reduction in major cardiac
      events.

PMID- 22464105
TI  - Sodium nitrite: the "cure" for nitric oxide insufficiency.
AB  - This process of "curing" food is a long practice that dates back thousands of
      years long before refrigeration or food safety regulations. Today food safety and
      mass manufacturing are dependent upon safe and effective means to cure and
      preserve foods including meats. Nitrite remains the most effective curing agent
      to prevent food spoilage and bacterial contamination. Despite decades of rigorous
      research on its safety and efficacy as a curing agent, it is still regarded by
      many as a toxic undesirable food additive. However, research within the
      biomedical science community has revealed enormous therapeutic benefits of
      nitrite that is currently being developed as novel therapies for conditions
      associated with nitric oxide (NO) insufficiency. Much of the same biochemistry
      that has been understood for decades in the meat industry has been rediscovered
      in human physiology. This review will highlight the fundamental biochemistry of
      nitrite in human physiology and highlight the risk benefit evaluation surrounding
      nitrite in food and meat products. Foods or diets enriched with nitrite can have
      profound positive health benefits.

PMID- 22464107
TI  - The outcome of extra-abdominal fibromatosis treated at a tertiary referral
      centre.
AB  - PURPOSE: To review the outcomes of patients with extra-abdominal fibromatosis
      treated at a tertiary referral centre. METHODS: A retrospective review of a
      series of 72 patients with fibromatosis treated at the Royal National Orthopaedic
      Hospital (RNOH) between 1980 and 2009, with a median follow up of 4 years (1-17
      years). RESULTS: Forty patients were primary referrals, and 32 more had
      operations at the referring hospital. Five were treated non-operatively; 48
      patients were treated by operation alone and 19 patients underwent surgery
      supplemented by adjuvant therapy. Recurrence was seen in 24 of the operation
      alone group and 10 in the operation and adjuvant therapy group. The rate of
      recurrence was lower with complete excision. However, complete excision was
      impossible in some cases because of extension into the chest or spinal canal, or
      involvement with the axial vessels and lumbosacral or brachial plexus.
      CONCLUSION: We suggest that operative excision should seek to preserve function
      and that supplementary adjuvant therapy may reduce the risk of recurrence,
      although excision margin appears to be the most important factor. The aggressive,
      infiltrative behaviour of deep fibromatoses and the associated genetic mutations
      identified, clearly distinguish them from the superficial fibromatoses and makes
      their treatment more difficult and dangerous, especially where vital structures
      are involved.

PMID- 22464106
TI  - Small non-coding RNAs mount a silent revolution in gene expression.
AB  - During the past decade, it has become evident that small non-coding RNAs (ncRNAs)
      participate in widespread and essential regulatory mechanisms in most eukaryotic
      cells. Novel classes of small RNAs, their biogenesis pathways and cellular
      effects are continuously being described, and new properties of already
      established ncRNAs are still being discovered. As the list of small RNA molecules
      and their roles becomes more and more extensive, one can get lost in the midst of
      new information. In this review, we attempt to bring order to the small ncRNA
      transcriptome by covering some of the major milestones of recent years. We go
      through many of the new properties that have been attributed to already familiar
      RNA molecules, and introduce some of the more recent novel classes of tiny
      ncRNAs.

PMID- 22464109
TI  - Sonoelectrochemical synthesis and assembly of bismuth-antimony alloy: from
      nanocrystals to nanoflakes.
AB  - Bismuth-based nanostructures have attracted growing interest because of their
      promising thermoelectric properties and applications in optics and electronics.
      Pulsed sonoelectrochemical technique was selected to fabricate bismuth-antimony
      (BiSb) flake-like alloy in ethylene glycol aqueous solution. The formation
      mechanism for the BiSb alloy was discussed. Ultrasonic played an important role
      in regenerating electrode and promoting the formation of BiSb nanoflakes. Citrate
      and polyvinylpyrrolidone (PVP) were introduced as mixed controlling agents during
      the nucleation and growth process.

PMID- 22464108
TI  - Ultrasound and microwave assisted synthesis of isoindolo-1,2-diazine: a
      comparative study.
AB  - A comparative study, ultrasound (US) versus microwave (MW) versus conventional
      thermal heating (TH), for synthesis of isoindolo-1,2-diazine is described. The
      reaction pathway is fast, efficient and straight applicable, involving a Huisgen
      [3+2] dipolar cycloaddition of cycloimmonium ylides to 1,4-naphthoquinone. A
      feasible reaction mechanism for the obtaining of the fully aromatized tetra- and
      penta- cyclic isoindolo-1,2-diazine is presented. Under US irradiation the yields
      are much higher (sometimes substantially, by almost double), the reaction time
      decreases substantially, the reaction conditions are milder. The use of a
      generator with a higher nominal power induces higher yields and short reaction
      times. Overall the use of US it proved to be more efficient than MW or TH. A
      feasible explication for US efficiency is presented.

PMID- 22464110
TI  - The ARTT of palpation?

PMID- 22464111
TI  - Weaving a mat of fascia research.

PMID- 22464112
TI  - Acute repetitive lumbar syndrome: a multi-component insight into the disorder.
AB  - PURPOSE: Repetitive Lumbar Injury (RLI) is common in individuals engaged in long
      term performance of repetitive occupational/sports activities with the spine. The
      triggering source of the disorder, tissues involved in the failure and
      biomechanical, neuromuscular, and biological processes active in the initiation
      and development of the disorder, are not known. The purpose is, therefore, to
      test, using in-vivo feline model and healthy human subjects, the hypothesis that
      RLI due to prolonged exposure to repetitive lumbar flexion-extension is triggered
      by an acute inflammation in the viscoelastic tissues and is characterized by
      lingering residual creep, pronounced changes in neuromuscular control and
      transient changes in lumbar stability. This report, therefore, is a summary of a
      lengthy research program consisting of multiple projects. METHODS: A series of
      experimental data was obtained from in-vivo feline groups and normal humans
      subjected to prolonged cyclic lumbar flexion-extension at high and low loads,
      high and low velocities, few and many repetitions, as well as short and long in
      between rest periods, while recording lumbar displacement and multifidi EMG.
      Neutrophil and cytokines expression analysis were performed on the dissected
      feline supraspinous ligaments before loading (control) and 7 h post-loading. A
      comprehensive, time based model was designed to represent the creep, motor
      control, tissue biology and stability derived from the experimental data.
      RESULTS: Prolonged cyclic loading induced creep in the spine, reduced muscular
      activity, triggered spasms and reduced stability followed, several hours later,
      by acute inflammation/tissue degradation, muscular hyperexcitability and
      hyperstability. Fast movement, high loads, many repetitions and short rest
      periods, triggered the full disorder, whereas low velocities, low loads, long
      rest and few repetitions, triggered only minor but statistically significant pro
      inflammatory tissue degradation and significantly reduced stability. CONCLUSION:
      Viscoelastic tissue failure via inflammation is the source of RLI and is also the
      process which governs the mechanical and neuromuscular characteristic symptoms of
      the disorder. The experimental data validates the hypothesis and provides
      insights into the development of potential treatments and prevention.

PMID- 22464113
TI  - Mathematical model of fiber orientation in anisotropic fascia layers at large
      displacements.
AB  - A mathematical model is developed to determine the relationship between stretch
      and the orientation of fibers in the fascia. The transversely isotropic stress-
      strain relation for large displacements valid for the human fascia reinforced by
      the collagen fibers is employed. The relation between the orientation of fibers
      in the un-deformed and deformed state depending upon the stretch is plotted. It
      is observed that for greater fiber angle orientation, the fibers are more
      resistant to reorientation as the fascia is stretched longitudinally. It is also
      concluded that the reinforced fascia will always be in tension as the stretch is
      applied. However, we suggest future research to resolve the tension and
      compression issues in fascia.

PMID- 22464114
TI  - Musculoskeletal myths.
AB  - This paper discusses a number of common myths in the musculoskeletal pain
      management and rehabilitation/athletic development fields. The origins or
      rationale for these beliefs are reviewed. New scientific evidence disputing or
      refuting the myth is then presented followed by and explanation and evidence for
      an updated perspective.

PMID- 22464115
TI  - Development of active myofascial trigger points in neck and shoulder musculature
      is similar after lumpectomy or mastectomy surgery for breast cancer.
AB  - Our aim was to describe the differences in the presence of myofascial trigger
      points (TrPs) in neck and shoulder muscles after 2 surgery approaches for breast
      cancer: mastectomy or lumpectomy. Thirty-two women (mean age: 50 +/- 7 years) who
      received lumpectomy, 16 women (mean age: 48 +/- 10 years) who had received
      mastectomy after breast cancer, and 16 women (mean age: 49 +/- 9 years) with
      breast cancer who had not received either surgical treatment, participated.
      Myofascial TrPs in the upper trapezius, sternocleidomastoid, levator scapulae,
      scalene, infraspinatus and pectoralis major muscles were bilaterally explored by
      an assessor blinded to the women's condition. TrPs were considered active when
      palpation reproduced local and referred pain symptoms recognized by the patient
      as familiar pain symptoms. The number of active TrPs within mastectomy (mean +/-
      SD: 4.6 +/- 1) and lumpectomy (mean +/- SD: 4.5 +/- 1) groups was significantly
      higher (P < 0.001) as compared to the control group (mean +/- SD: 1.1 +/- 1.3),
      but not significantly different between them (P = 0.641). Women who received
      either lumpectomy or mastectomy showed similar distribution of active TrPs and a
      higher prevalence of active TrPs as compared to the control group. Active TrPs in
      the pectoralis major muscle were the most prevalent in both surgery groups The
      number of active TrPs was weakly correlated with neck (r(s) = 0.385; P = 0.029)
      and shoulder/axillary (r(s) = 0.397; P = 0.024) pain intensity within the
      lumpectomy, but not the mastectomy group. This study found active TrPs in neck
      and shoulder musculature in women who had received lumpectomy or mastectomy. The
      induced local and referred pain pattern from active TrPs reproduced neck and
      shoulder/axillary symptoms and pain patterns in women after breast cancer
      surgery. Few active TrPs were found in a control group of women with breast
      cancer who had not received any surgical treatment.

PMID- 22464116
TI  - The effectiveness of the Pilates method: reducing the degree of non-structural
      scoliosis, and improving flexibility and pain in female college students.
AB  - OBJECTIVE: To evaluate the effectiveness of Pilates with regard to the degree of
      scoliosis, flexibility and pain. METHOD: The study included 31 female students
      divided into two groups: a control group (CG = 11), which had no therapeutic
      intervention, and an experimental group (EG = 20), which underwent Pilates-based
      therapy. We used radiological goniometry measurements to assess the degree of
      scoliosis, standard goniometry measurements to determine the degree of
      flexibility and the scale of perceived pain using the Borg CR 10 to quantify the
      level of pain. RESULTS: The independent t test of the Cobb angle (t = - 2.317, p
      = 0.028), range of motion of trunk flexion (t = 3.088, p = 0.004) and pain (t = 
      2.478, p = 0.019) showed significant differences between the groups, with best
      values in the Pilates group. The dependent t test detected a significant decrease
      in the Cobb angle (Delta% = 38%, t = 6.115, p = 0.0001), a significant increase
      in trunk flexion (Delta% = 80%, t = -7.977, p = 0.0001) and a significant
      reduction in pain (Delta% = 60%, t = 7.102, p = 0.0001) in the EG. No significant
      difference in Cobb angle (t = 0.430, p = 0.676), trunk flexion, (t = 0.938p =
      0.371) or pain (t = 0.896, p = 0.391) was found for the CG. CONCLUSION: The
      Pilates group was better than control group. The Pilates method showed a
      reduction in the degree of non-structural scoliosis, increased flexibility and
      decreased pain.

PMID- 22464117
TI  - Electromyographic analysis of masseter and anterior temporalis muscle in sleep
      bruxers after occlusal splint wearing.
AB  - Bruxism is widely defined as an anxiety response to environmental stress.
      Occlusal splints are frequently used in sleep bruxism, to protect teeth from
      damage resulting from the contraction force of mandibular muscles, or to reduce
      the orofacial pain by relaxing masticatory muscles. Surface electromyography
      (EMG) of the right and left masseter and temporalis muscles was performed in 15
      women presenting sleep bruxism and temporomandibular disorders related to
      occupational stress, after nocturnal use of the occlusal splint. The EMG signals
      were recorded twice per patient: After a work shift (pre-splint) and after a
      night of sleep with the occlusal splint (post-splint) before a new workday. The
      parametric t-paired test was used to compare differences of the RMS amplitude
      between pre and post-splint records, for resting and maximal clenching effort.
      The level of significance for each comparison was set to p < 0.05. The results of
      the study supports the premise that the use of occlusal splint reduces EMG
      activity in the masseter and anterior temporalis muscles, in patients who
      presented with sleep bruxism related to occupational stress.

PMID- 22464119
TI  - Reliability of photogrammetry in the evaluation of the postural aspects of
      individuals with structural scoliosis.
AB  - PURPOSE: The purpose of this study was to investigate the reliability of
      photogrammetry in the measurement of the postural deviations in individuals with
      idiopathic scoliosis. METHODS: Twenty participants with scoliosis (17 women and
      three men), with a mean age of 23.1 +/- 9 yrs, were photographed from the
      posterior and lateral views. The postural aspects were measured with CorelDRAW
      software. RESULTS: High inter-rater and test-retest reliability indices were
      found. It was observed that with more severity of scoliosis, greater were the
      variations between the thoracic kyphosis and lumbar lordosis measures obtained by
      the same examiner from the left lateral view photographs. A greater body mass
      index (BMI) was associated with greater variability of the trunk rotation
      measures obtained by two independent examiners from the right, lateral view (r =
      0.656; p = 0.002). The severity of scoliosis was also associated with greater
      inter-rater variability measures of trunk rotation obtained from the left,
      lateral view (r = 0.483; p = 0.036). CONCLUSIONS: Photogrammetry demonstrated to
      be a reliable method for the measurement of postural deviations from the
      posterior and lateral views of individuals with idiopathic scoliosis and could be
      complementarily employed for the assessment procedures, which could reduce the
      number of X-rays used for the follow-up assessments of these individuals.

PMID- 22464118
TI  - Yoga and massage therapy reduce prenatal depression and prematurity.
AB  - Eighty-four prenatally depressed women were randomly assigned to yoga, massage
      therapy or standard prenatal care control groups to determine the relative
      effects of yoga and massage therapy on prenatal depression and neonatal outcomes.
      Following 12 weeks of twice weekly yoga or massage therapy sessions (20 min each)
      both therapy groups versus the control group had a greater decrease on
      depression, anxiety and back and leg pain scales and a greater increase on a
      relationship scale. In addition, the yoga and massage therapy groups did not
      differ on neonatal outcomes including gestational age and birthweight, and those
      groups, in turn, had greater gestational age and birthweight than the control
      group.

PMID- 22464120
TI  - Reliability testing of the patellofemoral joint reaction force (PFJRF)
      measurement during double-legged squatting in healthy subjects: a pilot study.
AB  - INTRODUCTION: Anterior knee pain or patellofemoral pain syndrome (PFPS) is
      supposed to be related to patellofemoral joint reaction forces (PFJRF). Measuring
      these forces may therefore provide reliable evidence for conservative treatments
      to correct probable malalignment in subjects with PFPS. The aim of the present
      study was to examine the reliability of PFJRF measurements during double-legged
      squatting in healthy subjects. METHODS: Using a motion analysis system and one
      forceplate, PFJRF of 10 healthy subjects were assessed during double-legged
      squatting. Data were collected from superficial markers taped to selected
      landmarks. This procedure was performed on the right knees, at three different
      knee flexion angles of 30, 45 and 60 degrees  during three separate double-legged
      squats. Subjects were then requested to repeat this test procedure on two
      separate test sessions at different occasions. The PFJRF was calculated using a
      biomechanical model of the patellofemoral joint. RESULTS: The data reveal an
      increase in PFJRF values (from mean, SD of 425.2, 35.5N to 1075.4, 70.1N)with an
      increase in the tibiofemoral joint angle during double-legged squatting. The CV
      (coefficient of variation) values during within and between session tests,
      revealed the high repeatability and reproducibility of PFJRF measurements, while
      the ICC (intra class correlation coefficient) values showed the low reliability
      of these measurements. CONCLUSION: The low reliability of PFJRF measurements
      suggests that the PFJRF measurement during double-legged squatting should be
      performed with caution with improving the method of kinetic measurement of the
      patellofemoral joint in healthy subjects.

PMID- 22464121
TI  - Postural control under visual and proprioceptive perturbations during double and
      single limb stances: insights for balance training.
AB  - Single Limb Stance under visual and proprioceptive disturbances is largely used
      in clinical settings in order to improve balance in a wide range of functional
      disabilities. However, the proper role of vision and proprioception in SLS is not
      completely understood. The objectives of this study were to test the hypotheses
      that when ankle proprioception is perturbed, the role of vision in postural
      control increases according to the difficulty of the standing task. And to test
      the effect of vision during postural adaptation after withdrawal of the
      somesthetic perturbation during double and single limb stance Eleven males were
      submitted to double (DLS) and single limb (SLS) stances under conditions of
      normal or reduced vision, both with normal and perturbed proprioception. Center
      of pressure parameters were analyzed across conditions. Vision had a main effect
      in SLS, whereas proprioception perturbation showed effects only during DLS.
      Baseline stability was promptly achieved independently of visual input after
      proprioception reintegration. In conclusion, the role of vision increases in SLS.
      After proprioception reintegration, vision does not affect postural recovery.
      Balance training programs must take that into account.

PMID- 22464122
TI  - Lifelong physical activity affects mini mental state exam scores in individuals
      over 55 years of age.
AB  - INTRODUCTION: The positive effects of physical activity on cognition have been
      widely documented. Human studies and the results obtained from animal models of
      Alzheimer's disease (AD) have shown that if commenced early in life, exercise
      effectively reduces the development of cognitive deficits caused by aging. In the
      present study, the scores on Mini Mental State Exam (MMSE) of individuals over 55
      years old who had a history of exercising have been compared to those without a
      history of exercising. METHODS: This research was carried out on 273 individuals
      over 55 years of age. The subjects were randomly chosen from different areas of
      Mashhad and from exercise clubs. Each person completed a personal information
      form containing data such as demographics in addition to details of their
      involvement in sporting activity. Subjects were categorized as follows: 1- non
      exercised, 2- exercised. The people in group 2 were then divided into non
      professionally exercised (with a history of 2-10 years exercising) or
      professionally--exercised subjects (i.e. people who were currently, or had
      previously been members of an exercise club and/or had been trained for at least
      10 years). RESULT: Out of 273 subjects questioned in the present study, 229 were
      males and 44 were females. The MMSE score in men was significantly higher than
      women (p < 0.001). The exercised individuals of both sexes had significantly
      higher scores compared to non-exercised group (p < 0.001). There was no
      significant difference between professionally- exercised individuals of either
      sex in comparison with exercised ones. CONCLUSION: It is suggested that lifelong
      physical activity and exercise affects cognitive performance in old age.

PMID- 22464123
TI  - Effect of flexibility exercise on lumbar angle: a study among non-specific low
      back pain patients.
AB  - The study investigated the influence of lumbar flexibility exercise on the lumbar
      angle among patients with non-specific low back pain (LBP). Pre-experimental one
      group pretest-posttest design trial was conducted at Health Service Center,
      Chulalongkorn University, Thailand. Thirty-five non-specific LBP patients with
      limitation in lower back range of motion and without neurological deficits were
      recruited (based on the LBP guidelines by RCGP 1999). Lumbar flexibility exercise
      program developed based on McKenzie therapy was performed individually each day
      for 2 weeks. Patients attended an exercise program daily in the first week under
      the supervision of a physiotherapist. The exercise program consisted of 7 sets a
      day (3-2-2 in the morning-afternoon-evening) in series of 10 repetitions for each
      set for 2 weeks. Lumbar angle was measured at the beginning and at the end of 2
      weeks in order to determine the range of motion improved. The results indicated
      that the low back pain symptom improved as well as the angle.

PMID- 22464124
TI  - Immediate beneficial effects of self-monitoring body movements for upright
      postural stability in young healthy individuals.
AB  - OBJECTIVE: The present study is an investigation of whether an intervention
      involving awareness of joint movement without vision (i.e., self-monitoring)
      contributes to improved stability of upright posture as measured immediately
      after self-monitoring. METHODS: Eighteen young adults (ages: 22.6 +/- 2.2 years)
      participated in two interventions: self-monitoring and control. In the self
      monitoring intervention, the blindfolded participants tried to reproduce a target
      angle using both the ankle and the wrist while self-monitoring the movement. In
      the control intervention, they performed the same task while continuously
      performing an arithmetic subtraction task. RESULTS: Pre-post measurements of
      postural stability using a force plate for each intervention showed that self
      monitoring significantly improved the stability of unipedal posture but not that
      of bipedal posture. Such beneficial effect for unipedal posture was obtained even
      when the participant monitored the wrist movement. CONCLUSIONS: Self-monitoring
      was effective to improve postural stability in cases in which maintaining the
      whole body balance was challenging.

PMID- 22464125
TI  - Reproducibility of the pressure biofeedback unit in measuring transversus
      abdominis muscle activity in patients with chronic nonspecific low back pain.
AB  - The Pressure Biofeedback Unit (PBU) is often used by clinicians and researchers
      to indirectly evaluate transversus abdominis (TrA) muscle activity. The purpose
      of this study was to evaluate the inter and intra-examiner reproducibility of the
      PBU in measuring TrA muscle activity in fifty patients with chronic nonspecific
      low back pain. This study was performed using a test-retest design with a seven
      day interval. An Intraclass Correlation Coefficient (ICC(2,1)) of 0.74 (95% CI
      0.54 to 0.85) and 0.76 (95% CI 0.58 to 0.86) was observed for the intra and inter
      examiner reproducibility, respectively. The intra-examiner agreement (Limits of
      Agreement - LOA = 2.1 to -1.8 mmHg) and the inter-examiner agreement (LOA = 2.0
      to -1.9 mmHg) were within the limits of agreement on 95% of occasions. The
      reproducibility of PBU in measuring TrA muscle activity in patients with chronic
      nonspecific low back pain ranged from satisfactory to excellent.

PMID- 22464126
TI  - The Yin & Yang of rehabilitation & performance.

PMID- 22464127
TI  - Rebalancing the Autonomic Nervous System (ANS) with work in exercises: practical
      applications.

PMID- 22464128
TI  - The serratus punch.

PMID- 22464129
TI  - BioLemmatizer: a lemmatization tool for morphological processing of biomedical
      text.
AB  - BACKGROUND: The wide variety of morphological variants of domain-specific
      technical terms contributes to the complexity of performing natural language
      processing of the scientific literature related to molecular biology. For
      morphological analysis of these texts, lemmatization has been actively applied in
      the recent biomedical research. RESULTS: In this work, we developed a domain
      specific lemmatization tool, BioLemmatizer, for the morphological analysis of
      biomedical literature. The tool focuses on the inflectional morphology of English
      and is based on the general English lemmatization tool MorphAdorner. The
      BioLemmatizer is further tailored to the biological domain through incorporation
      of several published lexical resources. It retrieves lemmas based on the use of a
      word lexicon, and defines a set of rules that transform a word to a lemma if it
      is not encountered in the lexicon. An innovative aspect of the BioLemmatizer is
      the use of a hierarchical strategy for searching the lexicon, which enables the
      discovery of the correct lemma even if the input Part-of-Speech information is
      inaccurate. The BioLemmatizer achieves an accuracy of 97.5% in lemmatizing an
      evaluation set prepared from the CRAFT corpus, a collection of full-text
      biomedical articles, and an accuracy of 97.6% on the LLL05 corpus. The
      contribution of the BioLemmatizer to accuracy improvement of a practical
      information extraction task is further demonstrated when it is used as a
      component in a biomedical text mining system. CONCLUSIONS: The BioLemmatizer
      outperforms other tools when compared with eight existing lemmatizers. The
      BioLemmatizer is released as an open source software and can be downloaded from
      http://biolemmatizer.sourceforge.net.

PMID- 22464130
TI  - Fused bicycles as arylketone bioisosteres leading to potent, orally active
      thiadiazole H3 antagonists.
AB  - A structure-activity relationship study was undertaken to address the lack of
      oral exposure of the H3 antagonist 1, which incorporated an arylketone. Among a
      number of sub-series, the 4H-pyrido[1,2-a]pyrimidin-4-one analog 21 showed an
      improved PK profile in rat and mouse and was active in an obesity model. The
      pyrimidin-4-one proved to be a novel and useful ketone bioisostere.

PMID- 22464131
TI  - Design, synthesis, and biological activity of novel 1,4-disubstituted
      piperidine/piperazine derivatives as CCR5 antagonist-based HIV-1 entry
      inhibitors.
AB  - A series of novel 1,4-disubstituted piperidine/piperazine derivatives were
      designed, synthesized and evaluated for their in vitro activities against HIV-1
      Bal (R5) infection in CEMX174 5.25M7 cells. A majority of these compounds showed
      potent anti-HIV-1 activities with IC(50) at nanomolar levels. N-(4-Fluoro
      benzyl)piperazine analog B07 hydrochloride exhibited potency against HIV-1
      activity similar to that of TAK-220 hydrochloride, but it had much better water
      solubility (25 mg/ml in phosphate sodium buffer at 25  degrees C) and oral
      bioavailability (56%) than TAK-220 hydrochloride (a solubility of 2 mg/ml and
      oral bioavailability of 1.4%). These results suggest that B07 hydrochloride may
      serve as a better lead for the development of new anti-HIV-1 therapies or
      microbicides for treatment and prevent of HIV-1 infection.

PMID- 22464132
TI  - Analogs of the RSK inhibitor SL0101: optimization of in vitro biological
      stability.
AB  - The Ser/Thr protein kinase, RSK, is important in the etiology of tumor
      progression including invasion and motility. The natural product kaempferol-3-O
      (3",4"-di-O-acetyl-alpha-l-rhamnopyranoside), called SL0101, is a highly specific
      RSK inhibitor. Acylation of the rhamnose moiety is necessary for high affinity
      binding and selectivity. However, the acetyl groups can be cleaved by esterases,
      which accounts for the poor in vitro biological stability of SL0101. To address
      this problem a series of analogs containing acetyl group replacements were
      synthesized and their in vitro stability evaluated. Monosubstituted carbamate
      analogs of SL0101 showed improved in vitro biological stability while maintaining
      specificity for RSK. These results should facilitate the development of RSK
      inhibitors derived from SL0101 as anticancer agents.

PMID- 22464133
TI  - Penicacids A-C, three new mycophenolic acid derivatives and immunosuppressive
      activities from the marine-derived fungus Penicillium sp. SOF07.
AB  - Three new mycophenolic acid derivatives, penicacids A-C (1-3), together with two
      known analogues, mycophenolic acid (MPA, 4) and 4'-hydroxy-MPA (5), were isolated
      from a fungus Penicillium sp. SOF07 derived from a South China Sea marine
      sediment. The structures of compounds 1-3 were elucidated on the basis of MS and
      NMR ((1)H, (13)C, HSQC and HMBC) data analyses and comparisons with the known
      compounds. Structure-activity relationship studies of compounds 1-5 focused on
      inosine-monophosphate dehydrogenase inhibition revealed that hydroxylation at C
      4', methylation at C-7-OH, dual hydroxylation at C-2'/C-3' double bond of MPA
      diminished bioactivity whereas glucosyl hydroxylation at C-4' correlated to
      bioactivity comparable to that observed for MPA.

PMID- 22464134
TI  - Conformationally restricted novel pyrazole derivatives: synthesis of 1,8
      disubstituted 5,5-dimethyl-4,5-dihydro-1H-benzo[g]indazoles as a new class of
      PDE4 inhibitors.
AB  - A number of novel 1,8-disubstituted 5,5-dimethyl-4,5-dihydro-1H-benzo[g]indazoles
      based on a conformationally restricted pyrazole framework have been designed as
      potential inhibitors of PDE4. All these compounds were readily prepared by using
      simple chemistry strategy. The in vitro PDE4B inhibitory properties and molecular
      modeling studies of some of the compounds synthesized along with the X-ray single
      crystal data of a representative compound is presented.

PMID- 22464135
TI  - Training the next generation of radiology researchers. Report on a joint meeting
      of the Royal College of Radiologists and the Wellcome Trust and an overview of
      College strategies in developing radiology research.
AB  - As the use of imaging continues to increase in medical research, the Royal
      College of Radiologists (RCR) Research Committee and the Wellcome Trust held a
      joint meeting in 2010 to explore the current issues critical to training the next
      generation of radiology researchers. It was stated that despite an increase in
      consultant radiologist numbers, the number of academic posts has declined. This
      has resulted in radiology lagging behind some of the other specialties in terms
      of research activity and output. Some of the obstacles arising from the meeting
      have since been addressed by the RCR. These and other possible solutions that
      emanated from the interactive sessions include establishing a research culture in
      radiology departments, establishing a network of research radiologist mentors,
      improving trainee opportunities, and improving consultant opportunities. The
      meeting demonstrated the demand and need for extended support for research
      activity from the RCR. The RCR Academic Committee is formulating recommendations
      based on these and other sources of evidence. However, it is acknowledged that
      this comes at a time when national financial resources for research support are
      severely limited. Research in radiology remains an important part of the future
      development of the specialty. Supporting the next generation of potential
      researchers is essential, and this meeting was a means to understand how this
      might best be achieved.

PMID- 22464136
TI  - Pathologic erythrocyte deformability in patients with sudden sensorineural
      hearing loss.
AB  - OBJECTIVE: To evaluate if viscoelastic properties of blood influence suffering
      sudden sensorineural hearing loss and the capacity to respond after a specific
      therapy. PATIENTS AND METHODS: A longitudinal prospective study included 85 ears
      bearing sudden deafness. In them, the mean hearing loss compared to the healthy
      ear and the recovery ratio were measured at the onset and 6 months after a
      treatment with corticoids and piracetam. In addition, tinnitus or vestibular
      symptoms, whole blood filterability (WBF) and erythrocyte deformability -by means
      of the erythrocyte rigidity index (ERI)- were determined and noted at the
      beginning and the end of the study. RESULTS: Mean hearing loss was 30.3+/-19.7%
      at the onset, and 25.8+/-39% at the end. Forty-one ears showed a recovery of more
      than 75%. In these (48% of the entire study group), an increase in WBF and a
      decrease in ERI were observed (P<.001). Ears without tinnitus or vestibular
      crisis recovered more hearing at 6 months and showed a significant improvement in
      WBF and ERI, not detected among patients with these clinical findings. There were
      good correlations between mean hearing loss at onset and WBF, and between
      recovery and ERI at 6 months, but without statistical significance. Patients with
      arterial hypertension, cardiopathy and hypercholesterolemia were the most
      frequently detected, while hypertension and hyperuricaemia showed a better
      hearing recovery ratio. CONCLUSIONS: The blood viscosity parameters WBF and ERI
      offer useful information about the risk of suffering sudden deafness and the
      capacity to recover hearing with reactive therapies.

PMID- 22464137
TI  - [Prevalence of aphysiologic performance on dynamic posturography in work-related
      patients].
AB  - INTRODUCTION AND OBJECTIVES: Medical-legal implications of dizziness and
      imbalance in work-related patients are important. In these cases, computerized
      dynamic posturography (CDP) adds information to standard vestibular tests and
      aphysiologic patterns have been described. The objective is to assess the
      prevalence of aphysiologic performance on CDP in work-related patients
      complaining of dizziness/imbalance. MATERIAL AND METHODS: Retrospective review of
      patients referred by the workers' compensation board for assessment of dizziness,
      imbalance or both. Standard vestibular assessment including CDP was carried out
      in all patients. The sensory organization test (SOT) summaries were scored as
      normal, aphysiologic or vestibular using the scoring method published by Cevette
      et al. in 1995. RESULTS: Aphysiologic performance in SOT, evaluated with the
      Cevette formula, was found in 31 out of 100 cases. Low composite score results
      and aphysiologic SOT results had a statistically-significant association (P=.01).
      Videonystagmography (VNG) was altered in 14 out of 31 cases with aphysiologic
      SOT. CONCLUSION: The 31% prevalence of aphysiologic results on CDP among work
      related patients complaining of dizziness/imbalance is relatively high in
      comparison with the 25% published by Longridge and Mallinson in 2005. However,
      aphysiologic performance should not necessarily be related to malingering or
      exaggeration and altered vestibular tests are found in some of these cases.

PMID- 22464138
TI  - Practice nurses and obesity: professional and practice-based factors affecting
      role adequacy and role legitimacy.
AB  - AIM: This qualitative study explored the professional and practice-based factors
      affecting the role legitimacy and adequacy of practice nurses in managing obese
      patients. BACKGROUND: There are strong clinical, financial and practical reasons
      for tackling obesity in UK general practice. Although practice nurses may seem to
      be in an ideal position to manage obesity, there remain questions about their
      role adequacy (sense of self-efficacy in responding to patients' problems) and
      role legitimacy (their perceived boundaries of professional responsibility and
      right to intervene). METHODS: Semi-structured face-to-face interviews were
      conducted with 22 practice nurses in Lambeth, Southwark and Lewisham in South
      London. Interviews were digitally recorded and transcribed. Key themes were
      identified following coding of the data. Findings Factors that positively
      affected nurses' role adequacy and legitimacy were: their belief that obesity
      management was part of their chronic disease management and health promotion
      remit; their confidence in their own communication skills and ability to build
      rapport with patients; having attended training and being supported to take extra
      time for obesity management. Factors negatively affecting their role legitimacy
      and adequacy were: their low awareness and use of guidance; lack of knowledge of
      referral options; limited knowledge and use of non-medical and non-persuasive
      approaches; perceived lack of expertise in motivating patients, as well as in
      nutrition, child obesity and assessment; belief that there were some contexts in
      which it was more appropriate to raise the issue than others; lack of culturally
      appropriate materials and language barriers; belief that they had limited impact
      on outcome and that the patient is responsible for lack of success. Other factors
      negatively affecting their role adequacy and legitimacy included their
      ambivalence about the effectiveness of the interventions offered; perceived lack
      of priority for obesity management within practices; lack of time; workload and
      lack of clarity on protocols and roles within the practice.

PMID- 22464139
TI  - Duodenal involvement of mantle cell lymphoma observed by magnified endoscopy with
      narrow-band imaging.

PMID- 22464140
TI  - Prostaglandins and chronic inflammation.
AB  - Chronic inflammation is the basis of various chronic illnesses including cancer
      and vascular diseases. However, much has yet to be learned how inflammation
      becomes chronic. Prostaglandins (PGs) are well established as mediators of acute
      inflammation, and recent studies in experimental animals have provided evidence
      that they also function in transition to and maintenance of chronic inflammation.
      One role PGs play in such processes is amplification of cytokine signaling. As
      such, PGs can facilitate acquired immunity and induce long-lasting immune
      inflammation. PGs also contribute to chronic inflammation by making a positive
      feedback loop and/or by inducing chemokines and recruiting inflammatory cells to
      alternate active cell populations at affected sites. PGs also contribute to
      tissue remodeling as seen in angiogenesis and fibrosis. Although such roles of
      PGs should be verified in human diseases, these findings suggest that PG
      signaling is a promising therapeutic target of chronic inflammatory diseases.

PMID- 22464141
TI  - Reversal of lamina cribrosa displacement and thickness after trabeculectomy in
      glaucoma.
AB  - PURPOSE: To investigate the response of the lamina cribrosa (LC) and prelaminar
      tissue to glaucoma surgery using spectral-domain optical coherence tomography (SD
      OCT) and to determine the factors influencing such responses. DESIGN:
      Observational case series. PARTICIPANTS: Thirty-five eyes of 35 primary open
      angle glaucoma patients who underwent trabeculectomy. METHODS: Patients were
      imaged using a 10 * 15-degree rectangle covering the optic disc using SD-OCT.
      About 65 B-scans covering the optic discs were obtained using enhanced depth
      imaging SD-OCT before surgery, after 1 week, and 1, 3, and 6 months
      postoperatively. The pre- and postoperative magnitude of the LC displacement
      (distance from the Bruch's membrane opening plane to the level of anterior LC
      surface) and the thickness of LC and prelaminar tissue were determined on 7 to 13
      selected B-scan images in each eye. MAIN OUTCOME MEASURES: The amount of
      reduction in the LC displacement and changes in the thickness of LC and
      prelaminar tissue. RESULTS: Intraocular pressure (IOP) was decreased from 27.2 +/
      8.9 mmHg (range, 14-47) to 10.5 +/- 3.4 mmHg (range, 6-21) at postoperative
      month 6. The amount of posterior displacement of the LC was significantly
      decreased from a mean preoperative level of 614.58 +/- 179.57 to 503.90 +/-
      142.67 MUm at postoperative month 6 (P<0.001). The thicknesses of the LC and
      prelaminar tissue were significantly increased at postoperative month 6 (P<0.001
      and P = 0.048, respectively). The magnitude of the reduction in the LC
      displacement was significantly associated with younger age (P<0.001), greater
      percent IOP reduction (P = 0.019), and greater preoperative LC displacement (P =
      0.024). None of the factors was associated with the amount of LC or prelaminar
      tissue thickening. CONCLUSIONS: A significant reduction in the posterior
      displacement and increase in the thickness of the LC and prelaminar tissue were
      demonstrated after glaucoma surgery using enhanced depth imaging SD-OCT of the
      optic nerve head. The amount of reduction in the LC displacement was associated
      with younger age, larger baseline LC displacement, and greater IOP reduction.

PMID- 22464143
TI  - Letter to the editor regarding "A critical review of recombinant human
      morphogenetic protein-2 trials in spine surgery: emerging safety concerns and
      lessons learned".

PMID- 22464146
TI  - Solar regeneration of powdered activated carbon impregnated with visible-light
      responsive photocatalyst: factors affecting performances and predictive model.
AB  - This study demonstrated a green technique to regenerate spent powdered activated
      carbon (AC) using solar photocatalysis. The AC was impregnated with a
      photocatalyst photoexcitable under visible-light irradiation to yield a solar
      regenerable composite, namely nitrogen-doped titanium dioxide (N-TiO(2)/AC). This
      composite exhibited bifunctional adsorptive-photocatalytic characteristics.
      Contaminants of emerging environmental concern, i.e. bisphenol-A (BPA),
      sulfamethazine (SMZ) and clofibric acid (CFA) which exhibited varying affinities
      for AC were chosen as target pollutants. The adsorption of BPA and SMZ by the N
      TiO(2)/AC was significantly higher than that of CFA. The performance of solar
      photocatalytic regeneration (SPR) of the spent N-TiO(2)/AC composite generally
      increased with light intensity, N-TiO(2) loading and temperature. The
      regeneration efficiency (RE) for CFA-loaded spent composite was the highest
      compared to the other pollutant-loaded spent composites, achieving 77% within 8h
      of solar irradiation (765 W m(-2)). The rate-limiting process was pollutant
      desorption from the interior AC sorption sites. A kinetic model was developed to
      predict the transient concentration of the sorbate remaining in the spent
      composite during SPR. Comparison studies using solvent extraction technique
      indicated a different order of RE for the three pollutants, attributable to their
      varying solubilities in the aqueous and organic solvents.

PMID- 22464147
TI  - Cholesteryl Ester Transfer Protein (CETP) genotype and cognitive function in
      persons aged 35 years or older.
AB  - Common polymorphisms of the Cholestryl Ester Transfer Protein (CETP) gene may
      predict lower risk of cognitive decline. We investigated the association of
      cognitive function with CETP genotype in a population-based cohort of 4135
      persons aged 35-82 years. Cognitive function was measured with the Ruff Figural
      Fluency Test (RFFT; worst score, 0 points; best score, 175 points) and CETP I405V
      and Taq1B genotypes were determined by polymerase chain reaction. RFFT score was
      not associated with I405V genotype in persons aged 35-64 years. Remarkably,
      beyond age 65, homozygous valine carriers had higher RFFT scores than
      heterozygous carriers and noncarriers: RFFT (SD), 52 (21), 49 (18), and 47 (17)
      points, respectively (p = 0.005). There also was a statistically significant
      interaction between I405V genotype and age. Beyond age 65, the difference between
      homozygous valine carriers and noncarriers increased by 0.11 point per year (p =
      0.005). RFFT score was not associated with Taq1B genotype. In conclusion, CETP
      I405V valine homozygosity was associated with better cognitive function in
      persons aged 65 years or older.

PMID- 22464148
TI  - TNFalpha gene knockout differentially affects lipid deposition in liver and
      skeletal muscle of high-fat-diet mice.
AB  - AIMS/HYPOTHESIS: Inflammation and ectopic lipid deposition contribute to obesity
      related insulin resistance (IR). Studies have shown that deficiency of the
      proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) protects against
      the IR induced by a high-fat diet (HFD). We aimed to evaluate the relationship
      between HFD-related inflammation and lipid deposition in skeletal muscle and
      liver. EXPERIMENTAL DESIGN: Wild-type (WT) and TNFalpha-deficient (TNFalpha-KO)
      mice were subjected to an HFD for 12 weeks. A glucose tolerance test was
      performed to evaluate IR. Inflammatory status was assessed by measuring plasma
      and tissue transcript levels of cytokines. Lipid intermediate concentrations were
      measured in plasma, muscle and liver. The expression of genes involved in fatty
      acid transport, synthesis and oxidation was analyzed in adipose tissue, muscle
      and liver. RESULTS: HFD induced a higher body weight gain in TNFalpha-KO mice
      than in WT mice. The weight of epididymal and abdominal adipose tissues was
      twofold lower in WT mice than in TNFalpha-KO mice, whereas liver weight was
      significantly heavier in WT mice. IR, systemic and adipose tissue inflammation,
      and plasma nonesterified fatty acid levels were reduced in TNFalpha-KO mice fed
      an HFD. TNFalpha deficiency improved fatty acid metabolism and had a protective
      effect against lipid deposition, inflammation and fibrosis associated with HFD in
      liver but had no impact on these markers in muscle. CONCLUSIONS: Our data suggest
      that in an HFD context, TNFalpha deficiency reduced hepatic lipid accumulation
      through two mechanisms: an increase in adipose tissue storage capacity and a
      decrease in fatty acid uptake and synthesis in the liver.

PMID- 22464149
TI  - Lipoic acid administration prevents nonalcoholic steatosis linked to long-term
      high-fat feeding by modulating mitochondrial function.
AB  - Nonalcoholic steatosis is an important hepatic complication of obesity linked to
      mitochondrial dysfunction and insulin resistance. Furthermore, lipoic acid has
      been reported to have beneficial effects on mitochondrial function. In this
      study, we analyzed the potential protective effect of lipoic acid supplementation
      against the development of nonalcoholic steatosis associated with a long-term
      high-fat diet feeding and the potential mechanism of this effect. Wistar rats
      were fed on a standard diet (n=10), a high-fat diet (n=10) and a high-fat diet
      supplemented with lipoic acid (n=10). A group pair-fed to the latter group (n=6)
      was also included. Lipoic acid prevented hepatic triglyceride accumulation and
      liver damage in rats fed a high-fat diet (-68%+/-11.3% vs. obese group) through
      the modulation of genes involved in lipogenesis and mitochondrial beta-oxidation
      and by improving insulin sensitivity. Moreover, this molecule showed an
      inhibitory action on electron transport chain complexes activities (P<.01-P<.001)
      and adenosine triphosphate synthesis (P<.05), and reduced significantly energy
      efficiency. By contrast, lipoic acid induced an increase in mitochondrial copy
      number and in Ucp2 gene expression (P<.001 vs. obese). In summary, this
      investigation demonstrated the ability of lipoic acid to prevent nonalcoholic
      steatosis induced by a high-fat intake. Finally, the novelty and importance of
      this study are the finding of how lipoic acid modulates some of the mitochondrial
      processes involved in energy homeostasis. The reduction in mitochondrial energy
      efficiency could also explain, at least in part, the beneficial effects of lipoic
      acid not only in fatty liver but also in preventing excessive body weight gain.

PMID- 22464150
TI  - Maternal green tea extract supplementation to rats fed a high-fat diet
      ameliorates insulin resistance in adult male offspring.
AB  - Maternal overnutrition is associated with increased risk of metabolic disorders
      in the offspring. This study tested the hypothesis that maternal green tea (GT)
      supplementation can alleviate metabolic derangements in high-fat-diet-fed rats
      born of obese dams. Female Sprague-Dawley rats were fed low-fat (LF, 7%), high
      fat (HF, 30%) or HF diet containing 0.75% or 1.0% GT extract (GT1, GT2) prior to
      conception and throughout gestation and lactation. Both doses of GT significantly
      improved metabolic parameters of HF-fed lactating dams (P<.05). Birth weight and
      litter size of offspring from HF dams were similar, but GT supplementation led to
      lighter pups on day 21 (P<.05). The weaned male pups received HF, GT1 or GT2 diet
      (dam/pup diet groups: LF/HF, HF/HF, HF/GT1, HF/GT2, GT1/HF and GT2/HF). At week
      13, they had similar weight but insulin resistance index (IRI), serum
      nonesterified fatty acid (NEFA) and liver triglyceride of rats born to GT dams
      were 57%, 23% and 26% lower, accompanied by improved gene/protein expressions
      related to lipid and glucose metabolism, compared with the HF/HF rats (P<.05).
      Although HF/GT1 and HF/GT2 rats had lower serum NEFA, their insulin and IRI were
      comparable to HF/HF rats. This study shows that metabolic derangements induced by
      an overnourished mother could be offset by supplementing GT to the maternal diet
      and that this approach is more effective than giving GT to offspring since
      weaning. Hence, adverse effects of developmental programming are reversible, at
      least in part, by supplementing bioactive food component(s) to the mother's diet.

PMID- 22464151
TI  - Reduced expression of Raf-1 kinase inhibitory protein predicts regional lymph
      node metastasis and shorter survival in esophageal squamous cell carcinoma.
AB  - Raf-1 kinase inhibitory protein (RKIP), a suppressor of metastasis, is associated
      inversely with the progression and metastasis of human malignancies. The present
      study evaluated relationships between RKIP expression and metastatic potential,
      clinicopathological characteristics and patient outcome in esophageal squamous
      cell carcinoma (ESCC). We examined tissue specimens from 138 patients with
      thoracic ESCC. Using immunohistochemistry, RKIP expression was detected in ESCC
      in situ, primary ESCC and nodal metastatic ESCC. RKIP expression was reduced in
      28.9% (13/45) of ESCC in situ, in 50.0% (69/138) of primary ESCC and in 71.4%
      (65/91) of nodal metastatic ESCC. These levels of RKIP down-regulation differed
      significantly. RKIP expression was associated inversely with histological grade
      (P=0.008), pathological T stage (P=0.044), lymphatic invasion (P=0.019), regional
      lymph node metastasis (LNM; P=0.002) and stage (P=0.041). Pathological T stage
      (P=0.001), lymphatic invasion (P<0.001) and reduced RKIP expression (P=0.039)
      were independent predictors of regional LNM in ESCC. In addition, the
      postoperative survival of patients with RKIP-reduced ESCC was significantly
      shorter than for patients with RKIP-positive ESCC (P=0.004). Reduced RKIP
      expression in ESCC correlated with advanced disease, regional LNM and poor
      prognosis. RKIP expression may serve as a novel clinical biomarker in patients
      with ESCC.

PMID- 22464152
TI  - Anti-CD10 (56C6) expression in soft tissue sarcomas.
AB  - CD10 is known to be expressed in certain types of leukemia, in lymphomas and also
      in various types of carcinoma. However, data regarding CD10 expression in soft
      tissue sarcomas is scarce. Two hundred and two retrospective soft tissue sarcoma
      specimens were evaluated for CD10 expression immunohistochemically. The clinical
      records of these patients were reviewed, and clinical data was obtained for all
      patients. Our results showed that 90 of the 202 cases were found to express CD10.
      72% of malignant fibrous histiocytomas, 45% of fibrosarcomas, 34% of
      rhabdomyosarcomas, 50% of leiomyosarcomas, 22% of liposarcomas, 72% of malignant
      peripheral nerve sheath tumors, and 0% of the primitive neuroectodermal tumors
      were positive for CD10. Nearly half of the soft tissue sarcomas were found to
      express CD10. Stronger CD10 expression was found in high grade sarcomas.

PMID- 22464153
TI  - Revitalizing pathology laboratories in a gastrointestinal pathophysiology course
      using multimedia and team-based learning techniques.
AB  - In 2008, we changed the gastrointestinal pathology laboratories in a
      gastrointestinal pathophysiology course to a more interactive format using
      modified team-based learning techniques and multimedia presentations. The results
      were remarkably positive and can be used as a model for pathology laboratory
      improvement in any organ system. Over a two-year period, engaging and interactive
      pathology laboratories were designed. The initial restructuring of the
      laboratories included new case material, Digital Atlas of Video Education Project
      videos, animations and overlays. Subsequent changes included USMLE board-style
      quizzes at the beginning of each laboratory, with individual readiness assessment
      testing and group readiness assessment testing, incorporation of a clinician as a
      co-teacher and role playing for the student groups. Student responses for
      pathology laboratory contribution to learning improved significantly compared to
      baseline. Increased voluntary attendance at pathology laboratories was observed.
      Spontaneous student comments noted the positive impact of the laboratories on
      their learning. Pathology laboratory innovations, including modified team-based
      learning techniques with individual and group self-assessment quizzes, multimedia
      presentations, and paired teaching by a pathologist and clinical
      gastroenterologist led to improvement in student perceptions of pathology
      laboratory contributions to their learning and better pathology faculty
      evaluations. These changes can be universally applied to other pathology
      laboratories to improve student satisfaction.

PMID- 22464154
TI  - Pathological effects of dichlorvos and fenitrothion in mice.
AB  - Seeds of faba and soybeans were treated with dichlorvos (12 mg/kg) and
      fenitrothion (5 mg/kg) insecticides and stored for 30 weeks. The total internal
      residues of dichlorvos and fenitrothion amounted to about 69%, 73% and 67%, 74%
      in the applied doses in faba and soybeans, respectively. The pathological
      potential of dichlorvos and fenitrothion residues was studied by feeding mice for
      90 days with the treated seeds. Parallel studies were conducted in two control
      groups. Liver and kidney were taken for histological examinations. The results of
      blood biochemistry are supported by the histopathological changes observed in the
      liver and kidney of treated mice. Dichlorvos and fenitrothion insecticides caused
      degenerative changes in the liver and kidney of mice. Changes were more intense
      in mice which were given beans treated with dichlorvos than in mice fed on beans
      treated with fenitrothion. The livers of both treated groups showed an abnormal
      size and shape of hepatic cells. The kidneys of treated mice showed tubular
      vascular degeneration and lumen dilatation in both groups as compared with the
      control group.

PMID- 22464155
TI  - Molecular characterization of the antimicrobial resistance of Riemerella
      anatipestifer isolated from ducks.
AB  - The antimicrobial susceptibility of 103 Riemerella anatipestifer isolates
      obtained from ducks during 2008 and 2010 in Southern China, to 23 antimicrobial
      agents was investigated using the agar dilution method. The MIC(50) and MIC(90)
      values of streptomycin, kanamycin, gentamicin, apramycin, amikacin, neomycin,
      nalidixic acid and sulfadimidine were high (32->= 128 MUg/ml) among the 103 R.
      anatipestifer isolates. However, relatively low MIC(90) values (8 MUg/ml) of
      ampicillin and florfenicol were observed among these isolates. The presence of
      resistance genes and integrons was determined using PCR. The genes bla(TEM-1),
      aph(3')-VII, aadA1, aadA2, aac(3')-IV, aac(3')-IIc, aac(6')-Ib, cat2, cmlA, floR,
      tet(A), tet(B), tet(C), sul1, and sul2 were detected in 1, 2, 24, 35, 11, 4, 67,
      16, 26, 10, 6, 1, 9, 36 and 2 isolates, respectively. Twenty isolates contained
      one or two class 1 integrons carrying aadA2 or aac(6')-II-catB3-aadA1 gene
      cassette(s). Mutation analysis of the quinolone resistance-determining regions
      (QRDRs) of 43 R. anatipestifer isolates with nalidixic acid MICs >= 32 MUg/ml,
      showed that the most prevalent mutations in gyrA were those resulting in the
      amino acid exchanges Ser83-Ile (n=37), followed by Asp87-His (n=7) and Ser83-Arg
      (n=5). Point mutations in parC (Arg120-Glu) were observed in 5 isolates with a
      ciprofloxacin MIC of >16 MUg/ml. No plasmid-mediated quinolone resistance gene
      was detected. PFGE analysis showed that the clonal spread of multi-drug resistant
      R. anatipestifer isolates occurred in the same farm or between different farms.
      Our results reported, for the first time, the mechanism of quinolone resistance
      in R. anatipestifer.

PMID- 22464156
TI  - Multi-locus Sequence Analysis (MLSA) of Edwardsiella tarda isolates from fish.
AB  - Edwardsiella tarda is an enteric fish pathogen that has caused significant
      economic losses in a range of fish species residing in diverse ecological
      conditions. Several molecular methods relying on DNA fingerprinting (RAPD, RFLP
      and ERIC-PCR) and the gyrB gene marker have been used to characterize E. tarda
      isolates. However, all had drawbacks in resolving power and reproducibility. The
      present study was aimed at developing a novel Multi-locus Sequence Analysis
      (MLSA) scheme for genetic characterization of E. tarda isolates originating from
      multiple sources. MLSA has been described as an effective molecular tool with
      superior discriminatory power and reproducibility for exploring intra-species
      genetic diversity of several bacterial species. Nucleotide sequence fragments of
      eight protein coding housekeeping genes (gyrB, mdh, adk, dnaK, phoR, metG, pyrG
      and aroE2) were obtained from 23 fish pathogenic E. tarda isolates of different
      geographical origins, one human isolate and 3 reference strains. The phylogenetic
      relationships between isolates in individual gene analyses were not consistent,
      although some common patterns were apparent. Phylogenetic analysis based on
      concatenated sequences of seven gene loci, however, buffered the conflicting
      phylogenetic signals and resolved isolates according to their geographical origin
      and/or fish host. The MLSA revealed two major genetically diverging clusters in
      E. tarda isolates examined, one cluster representing isolates from fish and the
      other representing (in the main) human isolates, with E. ictaluri cluster
      situated in between. The results suggest, therefore, that the fish pathogenic E.
      tarda isolates may have been previously misclassified and probably represent one
      or more as yet unrecognized taxa within the genus Edwardsiella. The MLSA
      described here was robust enough in discriminating E. tarda isolates not only
      with respect to their geographical origins but also within different hosts from
      the same geographical location, high-lighting its potential application in
      tracing the source of infection and understand the epidemiological relationships
      among isolates of environmental, fish, other domestic animals or human origins.

PMID- 22464157
TI  - Comparative genomics of multiple plasmids from APEC associated with clonal
      outbreaks demonstrates major similarities and identifies several potential
      vaccine-targets.
AB  - Avian pathogenic Escherichia coli (APEC) is associated with several types of
      extraintestinal infections, collectively known as colibacillosis. A heterogeneous
      population structure has hindered development of vaccines protective against all
      APEC. Recently, however, the existence of different APEC subpathotypes have been
      suggested, which are defined by specific disease syndromes and associated
      virulence genes. A collection of 14 APEC isolates representing clonal outbreaks
      of salpingitis accompanied by peritonitis and sepsis were characterized in the
      present study. All the strains carried large plasmids and the aim of the study
      was to investigate the similarity of these by sequencing, annotating and
      comparative analysis to identify potential vaccine targets. In addition, a
      comparison with gene content of human extraintestinal E. coli (ExPEC) subtypes
      was conducted. Results obtained demonstrated highly similar plasmid contents of
      the 14 APEC strains, despite the diversity of their chromosomal background. All
      14 APEC carried the colicin V operon and numerous virulence genes. These included
      iss, traT, hlyF, eitABC, ompT, iroBCDEN, sitABCD, iutA and lucABCD. Several of
      these are shared with human ExPEC, implicating a possible zoonotic potential.
      Despite a diverse chromosomal background, it was concluded that the plasmid
      content of virulence genes are highly similar for the investigated APEC
      subpathotype. Based on their frequency, protein uniformity and subcellular
      localization iroN, iutA, iss, traT, ompT and etsC are suggested as vaccine
      candidates. Experimental studies are, however, necessary to determine the
      protective potential of the candidates against the APEC subpathotype
      characterized by salpingitis, peritonitis and possibly septicaemia.

PMID- 22464158
TI  - Neighborhood context and incidence of type 1 diabetes: the SEARCH for Diabetes in
      Youth study.
AB  - Findings regarding type 1 diabetes mellitus (T1DM) and neighborhood-level
      characteristics are mixed, with few US studies examining the influence of
      race/ethnicity. We conducted an ecologic study using SEARCH for Diabetes in Youth
      Study data to explore the association of neighborhood characteristics and T1DM
      incidence. 2002-2003 incident cases among youth at four SEARCH centers were
      included. Residential addresses were geocoded to US Census Tract. Standardized
      incidence ratios tended to increase with increasing education and median
      household income. Results from Poisson regression mixed models were similar and
      stable across race/ethnic groups and population density. Our study suggests a
      relationship of T1DM incidence with neighborhood-level socioeconomic status,
      independent of individual-level race/ethnic differences.

PMID- 22464159
TI  - Influences on body weight of female Moroccan migrants in the Netherlands: a
      qualitative study.
AB  - We aimed to gain insight into the influences on Moroccan migrant women's weight
      and weight-related behavior by enriching their perspectives with those of their
      non-migrant compatriots living in Morocco. In focus groups with migrant women in
      Amsterdam, participants attributed overweight to traditional Moroccan foods and
      food culture. In contrast, focus group participants in Morocco emphasized that
      overweight in migrants was largely due to their adoption of the Western diet.
      Results from women in both locations indicate a general lack of knowledge
      regarding appropriate physical activity. Migrants attributed their lower levels
      of physical activity to changes in lifestyle due to migration and reported having
      problems adjusting to these changes. All participants reported a cultural shift
      in preference towards slimmer body sizes. However, weight gain still tends to be
      seen as a sign of success. In designing interventions, universal approaches may
      be sufficient to address migration-related influences on behavior; however
      behavior that is driven by migrants' socio-cultural context may require more
      culturally appropriate strategies.

PMID- 22464160
TI  - [Use of freeze-dried plasma in the management of bleeding in a child with
      hemophilia in Djibouti].

PMID- 22464161
TI  - [Ultrasound evaluation of the nasogastric tube position in prehospital].
AB  - OBJECTIVE: To assess the feasibility and actual performance of ultrasound control
      in verification of the correct positioning of a nasogastric tube in pre-hospital
      settings. STUDY TYPE: Prospective, observational, single-centre study. PATIENTS
      AND METHODS: Correct positioning of nasogastric tubes in patients intubated in a
      pre-hospital setting was verified by ultrasound and routinely compared with the
      results of two pre-hospital tests, namely a test involving insufflation of air
      through a syringe coupled with epigastric auscultation and a test involving
      aspiration of gastric fluid with a syringe. Routine x-ray control was carried out
      and compared with the pre-hospital results. RESULTS: Ninety-six patients were
      included. Mean age was 52 years (median: 53.5 years, SD: 23 years). In 83% of the
      patients (n=80), the nasogastric tube was located by ultrasound immediately
      during the insertion procedure. The mean times to ultrasound confirmation of
      correct positioning of the nasogastric tube were 7s (median: 2s; SD: 16s) and 19s
      for the syringe tests (median 19s, SD: 5s). Eight ultrasound control tests were
      negative. Location coupled with insufflation of air through a syringe allowed
      detection of the nasogastric tube in the stomach but without providing
      confirmation of the actual gastric position. The pre-hospital ultrasound results
      were confirmed by subsequent radiological controls at the hospital. CONCLUSION:
      The ultrasound test performed in our study to verify correct positioning of a
      nasogastric tube is feasible in a pre-hospital setting. This technique is rapid
      and non-irradiating and is more sensitive and specific than the syringe tests
      commonly used in pre-hospital settings, and it may be performed in place of the
      latter tests.

PMID- 22464162
TI  - Brachial cuff measurements of blood pressure during passive leg raising for fluid
      responsiveness prediction.
AB  - OBJECTIVE: The passive leg raising maneuver (PLR) for fluid responsiveness
      testing relies on cardiac output (CO) measurements or invasive measurements of
      arterial pressure (AP) whereas the initial hemodynamic management during shock is
      often based solely on brachial cuff measurements. We assessed PLR-induced changes
      in noninvasive oscillometric readings to predict fluid responsiveness. STUDY
      DESIGN: Multicentre interventional study. PATIENTS AND METHODS: In ICU sedated
      patients with circulatory failure, AP (invasive and noninvasive readings) and CO
      measurements were performed before, during PLR (trunk supine, not modified) and
      after 500-mL volume expansion. Areas under the ROC curves (AUC) were determined
      for fluid responsiveness (>10% volume expansion-induced increase in CO)
      prediction. RESULTS: In 112 patients (19% with arrhythmia), changes in
      noninvasive systolic AP during PLR (noninvasiveDelta(PLR)SAP) only predicted
      fluid responsiveness (cutoff 17%, n=21, positive likelihood ratio [LR] of 26 [18
      38]), not unresponsiveness. If PLR-induced change in central venous pressure
      (CVP) was at least of 2 mm Hg (n=60), suggesting that PLR succeeded in altering
      cardiac preload, noninvasiveDelta(PLR)SAP performance was good: AUC of 0.94 [0.85
      0.98], positive and negative LRs of 5.7 [4.6-6.8] and 0.07 [0.009-0.5],
      respectively, for a cutoff of 9%. Of note, invasive AP-derived indices did not
      outperform noninvasiveDelta(PLR)SAP. CONCLUSION: Regardless of CVP (i.e., during
      "blind PLR"), noninvasiveDelta(PLR)SAP more than 17% reliably identified fluid
      responders. During "CVP-guided PLR", in case of sufficient change in CVP,
      noninvasiveDelta(PLR)SAP performed better (cutoff of 9%). These findings, in
      sedated patients who had already undergone volume expansion and/or
      catecholamines, have to be verified during the early phase of circulatory failure
      (before an arterial line and/or a CO measuring device is placed).

PMID- 22464163
TI  - [Postoperative brachial neuropathy, a rare aetiology: the Parsonage-Turner
      syndrome].

PMID- 22464164
TI  - [Preloading with HES 130/0.4 versus normal saline solution to prevent hypotension
      during spinal anaesthesia for elective caesarean section].
AB  - OBJECTIVE: To evaluate the efficacy of HES 130/0.4 preload compared to normal
      saline solution for prevention of hypotension during spinal anaesthesia for
      elective caesarean section. STUDY DESIGN: Prospective, randomized. PATIENTS AND
      METHODS: Sixty ASA I patients scheduled for elective caesarean section were
      randomized to receive either 1000 mL of normal saline solution preload (Group C)
      or 500 mL of HES 130/0.4 preload (Group V) within 15 minutes prior to spinal
      anaesthesia. Spinal anaesthesia techniques and ephedrine administration was
      standardized in both groups. The primary endpoint was the incidence of maternal
      hypotension before fetal extraction. RESULTS: The incidence of hypotension before
      fetal extraction was significantly lower in group V compared to group C (40% vs
      66%, P=0.03). Ephedrine consumption was significantly lower in group V (7.6 +/-
      13 mg vs 16.4 +/- 15 mg). Lowest systolic blood pressure was significantly higher
      in group V (96 +/- 14 vs 85 +/- 14 mmHg, P=0.005). Incidence of adverse maternal
      effects and neonatal consequences were similar in both groups. CONCLUSION: HES
      130/0.4 preload reduced the incidence of hypotension, the duration of longest
      hypotension, and the need for ephedrine during spinal anaesthesia for elective
      caesarean section. However, the efficacy of HES 130/0.4 alone in prevention of
      maternal hypotension during spinal anaesthesia for caesarean section is still
      insufficient.

PMID- 22464165
TI  - [Thigh haematoma after sciatic nerve block and fondaparinux].

PMID- 22464167
TI  - [New practices in anaesthesia. About the pressure-controlled ventilation in
      anaesthesia].

PMID- 22464166
TI  - [Massive transfusion: analysis of practices according to available medical
      devices].
AB  - INTRODUCTION: An assessment of practices and available medical devices during the
      treatment of a massive haemorrhage has been realised in the shock unit of our
      hospital. MATERIAL AND METHODS: Parameters influencing transfusion flow rate have
      been identified. Medical devices and equipment to accelerate the flow rate were
      analyzed on the basis of manufacturers' data and users opinion in relation with
      their practices. RESULTS: The system, from blood bags to venous access,
      influences flow rate: red blood cell viscosity, catheter and pressure gradient.
      Three types of acceleration systems are available: accelerated transfusion set,
      pressure cuff with a gravity blood IV set and fast-flow fluid warmers. Their
      benefits and disadvantages are presented and discussed. DISCUSSION: Maximum flow
      rates noted by manufacturers are not the real values because some parameters such
      as venous catheter diameter (limitative factor) and the red blood cell viscosity
      (diluted or not) are not considered. The choice of an infusion system is mainly
      based on the technical capacities (flow rate fluctuations, pressure gradient on
      blood bags, warming, air purging), practical modalities of use (medical devices
      and assembly) and cost. The pressure cuff with transfusion gravity set should be
      limited to non-critical situations or during the assembly of the fast flow fluid
      warmers (but no warming fluids, no air embolism prevention). The accelerated
      transfusion set is not the best option for a shock unit because it needs an
      operator permanently. The fast-flow fluid warmers are recommended for all types
      of massive haemorrhages, they are more secure but they require a long time to be
      assembled.

PMID- 22464168
TI  - Phosphoinositide binding by the Toll adaptor dMyD88 controls antibacterial
      responses in Drosophila.
AB  - The cell biological principles that govern innate immune responses in Drosophila
      are unknown. Here, we report that Toll signaling in flies was dictated by the
      subcellular localization of the adaptor protein dMyD88. dMyD88 was located at the
      plasma membrane by a process dependent on a C-terminal phosphoinositide-binding
      domain. In vivo analysis revealed that lipid binding by dMyD88 was necessary for
      its antimicrobial and developmental functions as well as for the recruitment of
      the downstream cytosolic adaptor Tube to the cell surface. These data are
      reminiscent of the interactions between the mammalian Toll adaptors MyD88 and
      TIRAP with one major exception. In the mammalian system, MyD88 is the cytosolic
      adaptor that depends on the phosphoinositide-binding protein TIRAP for its
      recruitment to the cell surface. We therefore propose that dMyD88 is the
      functional homolog of TIRAP and that both proteins function as sorting adaptors
      to recruit downstream signaling adaptors to activated receptors.

PMID- 22464169
TI  - Virus recognition by Toll-7 activates antiviral autophagy in Drosophila.
AB  - Innate immunity is highly conserved and relies on pattern recognition receptors
      (PRRs) such as Toll-like receptors (identified through their homology to
      Drosophila Toll) for pathogen recognition. Although Drosophila Toll is vital for
      immune recognition and defense, roles for the other eight Drosophila Tolls in
      immunity have remained elusive. Here we have shown that Toll-7 is a PRR both in
      vitro and in adult flies; loss of Toll-7 led to increased vesicular stomatitis
      virus (VSV) replication and mortality. Toll-7, along with additional
      uncharacterized Drosophila Tolls, was transcriptionally induced by VSV infection.
      Furthermore, Toll-7 interacted with VSV at the plasma membrane and induced
      antiviral autophagy independently of the canonical Toll signaling pathway. These
      data uncover an evolutionarily conserved role for a second Drosophila Toll
      receptor that links viral recognition to autophagy and defense and suggest that
      other Drosophila Tolls may restrict specific as yet untested pathogens, perhaps
      via noncanonical signaling pathways.

PMID- 22464170
TI  - Prostaglandin E2 suppresses antifungal immunity by inhibiting interferon
      regulatory factor 4 function and interleukin-17 expression in T cells.
AB  - T helper 17 (Th17) cells play an important role in mucosal host defense through
      production of the signature cytokines IL-17 and IL-22. Prostaglandin E2 (PGE2)
      has been shown to enhance IL-17 production by mature Th17 cells. However, when
      present during Th17 cell differentiation, we found that PGE2 inhibited the
      transcription factor IRF4 and suppressed production of IL-17 but not IL-22. We
      show that IRF4 was required for IL-17 expression but inhibited IL-22 expression,
      highlighting the potential for discordant regulation of these two cytokines in
      Th17 cells. The pathogenic fungus Cryptococcus neoformans produces PGE2, and we
      found that it uses PGE2- and IRF4-dependent mechanisms to specifically inhibit
      induction of IL-17 during Th17 cell differentiation. Blockade of host PGE2 during
      infection led to increased IL-17 production from CD4(+) T cells and increased
      survival of mice. These findings suggest that host- or pathogen-derived PGE2 can
      act directly on Th17 cells during differentiation to inhibit IL-17-dependent
      antimicrobial responses.

PMID- 22464173
TI  - Triglyceride: one molecule at the center of health and disease.

PMID- 22464171
TI  - Interleukin-2 inhibits germinal center formation by limiting T follicular helper
      cell differentiation.
AB  - T follicular helper (Tfh) cells promote T cell-dependent humoral immune responses
      by providing T cell help to B cells and by promoting germinal center (GC)
      formation and long-lived antibody responses. However, the cellular and molecular
      mechanisms that control Tfh cell differentiation in vivo are incompletely
      understood. Here we show that interleukin-2 (IL-2) administration impaired
      influenza-specific GCs, long-lived IgG responses, and Tfh cells. IL-2 did not
      directly inhibit GC formation, but instead suppressed the differentiation of Tfh
      cells, thereby hindering the maintenance of influenza-specific GC B cells. Our
      data demonstrate that IL-2 is a critical factor that regulates successful Tfh and
      B cell responses in vivo and regulates Tfh cell development.

PMID- 22464172
TI  - The adaptor protein Crk controls activation and inhibition of natural killer
      cells.
AB  - Natural killer (NK) cell inhibitory receptors recruit tyrosine phosphatases to
      prevent activation, induce phosphorylation and dissociation of the small adaptor
      Crk from cytoskeleton scaffold complexes, and maintain NK cells in a state of
      responsiveness to subsequent activation events. How Crk contributes to inhibition
      is unknown. We imaged primary NK cells over lipid bilayers carrying IgG1 Fc to
      stimulate CD16 and human leukocyte antigen (HLA)-E to inhibit through receptor
      CD94-NKG2A. HLA-E alone induced Crk phosphorylation in NKG2A(+) NK cells. At
      activating synapses with Fc alone, Crk was required for the movement of Fc
      microclusters and their ability to trigger activation signals. At inhibitory
      synapses, HLA-E promoted central accumulation of both Fc and phosphorylated Crk
      and blocked the Fc-induced buildup of F-actin. We propose a unified model for
      inhibitory receptor function: Crk phosphorylation prevents essential Crk
      dependent activation signals and blocks F-actin network formation, thereby
      reducing constraints on subsequent engagement of activation receptors.

PMID- 22464174
TI  - The 9th annual computational and systems neuroscience (cosyne) meeting.
AB  - The 9th annual Computational and Systems Neuroscience meeting (Cosyne) was held
      23-26 February in Salt Lake City, Utah. Cosyne meeting is the forum for exchange
      of experimental and theoretical/computational approaches to studying systems
      neuroscience.

PMID- 22464176
TI  - Antiepileptic drugs and vitamin B6 plasma levels in adult patients.
AB  - Treatment with several antiepileptic drugs (AED) is associated with lower serum
      concentrations of folate or vitamin B12. This prospective monocenter study
      analyzed vitamin B6 blood levels in 400 serial patients with epilepsy, AED
      treated (n=385), untreated (n=15) and healthy controls (n=233). The mean plasma
      vitamin B6 levels of the AED-treated (12.1+/-10.1; p=0.093) and the untreated
      patients (15.6+/-12.4; p=0.664) were not significantly different from the
      controls (13.9+/-15.2). These observations do not support the hypothesis that
      vitamin B6 blood levels are influenced by AED treatment.

PMID- 22464175
TI  - Variability of carbamazepine and valproate concentrations in elderly nursing home
      residents.
AB  - PURPOSE: Measuring antiepileptic drug (AED) concentrations is common practice in
      nursing homes. Phenytoin (PHT) concentrations fluctuate substantially in many
      nursing home residents under constant dose conditions; however, the stability of
      other AED concentrations has not been studied. We investigated the variability of
      carbamazepine (CBZ) and valproate (VPA) concentrations under constant dose
      conditions in US nursing home residents. METHODS: A database of elderly persons
      (>=65 years) in 119 nursing homes throughout the US was reviewed for residents
      with at least one measurement of total PHT, CBZ or VPA. Inclusion criteria for
      this study were three or more serum concentration measurements while on the same
      dose of CBZ or VPA, a two-month minimum stay, and no interfering co-medications
      (inducers or inhibitors). Enrollment occurred over a 2-year period. Data were
      collected on residents for a minimum of 6 months. KEY FINDINGS: Of the 593
      residents identified, 245 had CBZ or VPA concentrations measured and 44 (18%) met
      inclusion criteria (22 on CBZ and 22 VPA). Some subjects had little variability
      in AED concentrations, others had large fluctuations. Total CBZ concentrations
      within individuals varied as little as 0mg/L to as much as 6.3mg/L and total VPA
      concentrations as little as 10.0mg/L to as much as 77.6mg/L. SIGNIFICANCE: The
      variability of PHT, CBZ, and VPA concentrations in many but not all nursing home
      residents implies that a re-evaluation of the role of AED concentration
      measurements in the management of patients is needed. Strategies for use and
      interpretation of AED concentration measurements need to be reevaluated.

PMID- 22464177
TI  - Immunohistochemical features of claudin-low intrinsic subtype in metaplastic
      breast carcinomas.
AB  - PURPOSE: The claudin-low molecular subtype of breast cancer includes triple
      negative invasive carcinomas, with a high frequency of metaplastic and medullary
      features. The aim of this study was to evaluate the immunohistochemistry
      expression of claudins in a series of metaplastic breast carcinomas. We also
      assessed other claudin-low features, such as the cancer stem cell-like and
      epithelial-to-mesenchymal transition phenotypes. RESULTS: The majority of the
      cases showed weak or negative staining for membrane claudins expression. We found
      76.9% (10/13) low expressing cases for claudin-1, 84.6% (11/13) for claudin-3 and
      claudin-4, and 92.3% (12/13) for claudin-7. Regarding the cancer stem cell marker
      ALDH1, 30.8% (4/13) showed positive staining. We also showed that the majority of
      the cases presented a CD44(+)CD24(-/low) phenotype, positivity for vimentin and
      lack of E-cadherin expression. Interestingly, these claudin-low molecular
      features were specific of the mesenchymal component of metaplastic breast
      carcinomas, since its frequency was very low in other breast cancer molecular
      subtypes, as luminal, HER2-overexpressing and non-metaplastic triple negative
      tumors. CONCLUSIONS: The negative/low expression of claudins and E-cadherin, high
      levels of vimentin, and the breast cancer stem cell phenotype suggests that
      metaplastic breast carcinomas have similar features to the ones included in the
      claudin-low molecular subtype, specially their mesenchymal components.

PMID- 22464178
TI  - Parenting self-efficacy, parenting stress and child behaviour before and after a
      parenting programme.
AB  - AIM: To explore whether changes in parenting self-efficacy after attending a
      parenting programme are related to changes in parenting stress and child
      behaviour. BACKGROUND: Adverse parenting is a risk factor in the development of a
      range of health and behavioural problems in childhood and is predictive of poor
      adult outcomes. Strategies for supporting parents are recognised as an effective
      way to improve the health, well-being and development of children. Parenting is
      influenced by many factors including the behaviour and characteristics of the
      child, the health and psychological well-being of the parent and the contextual
      influences of stress and support. Parenting difficulties are a major source of
      stress for parents, and parenting self-efficacy has been shown to be an important
      buffer against parenting stress. METHODS: In all, 63 parents who had a child
      under the age of 10 years took part in the research. Of those, 58 returned
      completed measures of parenting self-efficacy, parenting stress and child
      behaviour at the start of a parenting programme and 37 at three-month follow-up.
      FINDINGS: Improvements in parenting self-efficacy and parenting stress were found
      at follow-up, but there was less evidence for improvements in child behaviour.
      The findings clearly suggest a relationship between parenting self-efficacy and
      parenting stress; parents who are feeling less efficacious experience higher
      levels of stress, whereas greater parenting self-efficacy is related to less
      stress. This study adds to the evidence that parent outcomes may be a more
      reliable measure of programme effectiveness than child outcomes at least in the
      short term.

PMID- 22464179
TI  - Current practice in management of the neck after chemoradiotherapy for patients
      with locally advanced oropharyngeal squamous cell carcinoma.
AB  - Patients whose necks respond completely to chemoradiation are unlikely to have
      residual viable tumour, which questions the need for planned neck dissection.
      Partial responders often need further assessment. Positron emission
      tomography/computed tomography (PET/CT) is becoming the standard method of
      assessing the response of both the primary site and neck to chemoradiation. There
      is debate, however, about the timing of assessment, the best imaging technique,
      and the extent of neck dissection, and emerging evidence supports more selective
      procedures with their attendant reductions in morbidity. Various trials have
      tried to settle these controversies, but we hypothesised that current practice
      varies across the United Kingdom (UK), so we set out to establish what it is. A
      total of 219 questionnaires were sent to head and neck surgeons of varying
      disciplines and their oncology counterparts, which outlined a clinical picture of
      a patient with persistent nodal disease after chemoradiotherapy, and requested
      information about the respondents' preferred choice and timing of investigations
      in addition to the type of neck dissection, if indicated. There were noticeable
      variations in practice, with a tendency towards personal choice rather than a
      multidisciplinary approach. Although there were some items of broad agreement,
      there was disparity about the timing of imaging and operation. There is
      inconsistency in the management of the neck in these patients in the UK, which
      may reflect an absence of guidelines and paucity of evidence-based information.
      We need to unify practice to improve the care of patients.

PMID- 22464180
TI  - Affected and unaffected quantitative aspects of grip force control in hemiparetic
      patients after stroke.
AB  - Adequate grip force modulation is critical to manual dexterity and often impaired
      in hemiparetic stroke patients. Previous studies in hemiparetic patients suggest
      that aspects of grip force control may be differently affected by the lesion. We
      developed a visuomotor power grip force-tracking task allowing quantification of
      tracking error, force variability and release duration. We investigated force
      control in 24 chronic stroke patients with varying severity of hemiparesis and in
      healthy control subjects. Force tracking was performed at 10, 20, and 30% maximal
      voluntary contraction (MVC). Control subjects were also tested at absolute force
      levels similar to those of the patients. Patients tracking with their paretic
      hand at similar relative (%MVC) grip force levels showed increased error, force
      variability and release duration, but surprisingly, there was no difference in
      tracking error or variability between patients and control subjects performing at
      similar absolute force levels. Furthermore, patients improved their tracking
      performance across repeated blocks similar to control subjects. Release duration,
      however, was increased (also in the non-paretic hand), was force-independent and
      did not correlate with MVC strength. Of the three performance measures, only
      release duration explained some of the variance in arm and hand function
      (Frenchay Arm Test score), independent of MVC strength. The findings show (i)
      that hemiparetic stroke patients preserve the ability to modulate (generate and
      maintain) power grip force within their limited force range and (ii) that MVC
      grip strength and duration of grip release are differently affected and are two
      complementary predictors of arm function after stroke.

PMID- 22464182
TI  - The acute response of the amygdalar TRH system to psychogenic stressors varies
      dependent on the paradigm and circadian condition.
AB  - Central administration of thyrotropin releasing hormone (TRH) reduces anxiety;
      amygdalar TRH expression is inversely proportional to the anxious behavior
      displayed in the elevated plus maze performed during the dark phase (EPM-D). To
      better understand the role of TRH in amygdala function, we evaluated the
      expression of TRH and the elements involved in its transmission in various
      stressful paradigms and how they associated with behavior. Wistar male rats were
      exposed to restraint (RES), EPM, or the open field test (OFT) and sacrificed 0-60
      min afterwards; OFT, RES and EPM were performed during the light (L), and OFT
      during the dark phase. Restraint increased amygdalar levels of proCRH mRNA,
      without change in proTRH. All paradigms augmented corticosterone release, highest
      after OFT-L that also enhanced proCRH mRNA levels and decreased those of proTRH.
      OFT-D activated the TRH system. Levels of anxiety or locomotion were similar in
      animals tested in light or dark phases but their association with biochemical
      parameters differed. ProTRH expression and TRH release correlated positively with
      decreased anxiety in EPM-L and in OFT-D. No association with anxiety was detected
      in OFT-L where proCRH and proTRH expression correlated with locomotion supporting
      their involvement in arousal. The responses of TRH amygdalar systems appeared
      modulated by the extent of the stress response and by the circadian conditions.
      Increased proTRH expression of animals exposed to OFT-D was specifically observed
      in the cortical nucleus of the amygdala, area involved in processing fear
      stimuli; these TRH neurons may thus be part of a circuit with anxiolytic
      properties.

PMID- 22464183
TI  - Sex-specific and region-specific changes in BDNF-TrkB signalling in the
      hippocampus of 5-HT1A receptor and BDNF single and double mutant mice.
AB  - Brain-derived neurotrophic factor (BDNF) and serotonin 5-HT1A receptors are
      implicated in the pathophysiology of depression and the mechanism of action of
      antidepressant drugs. Here, we explore possible reciprocal interactions of 5-HT1A
      receptor knockout and the expression of BDNF, its receptor TrkB and downstream
      mitogen-activated protein kinase (MAPK) in the ventral (VHP) and dorsal
      hippocampus (DHP). We compared female and male double mutant mice (5-HT1A(-/
      )/BDNF(+/-)) with single mutant mice (5-HT1A(-/-), BDNF(+/-)) and wildtype (WT)
      controls. Protein expression of BDNF, TrkB, phosphorylation of TrkB (pTrkB) and
      MAPKs (ERK1, ERK2) was examined using Western blot analysis (n=5-7). As expected,
      the BDNF(+/-) mice showed ~50% BDNF reduction. Loss of 5-HT1A receptors induced a
      significant decrease in BDNF levels in the VHP in female mice. The pTrkB/TrkB
      ratio was also significantly decreased in female 5-HT1A(-/-) mice and 5-HT1A(-/
      )/BDNF(+/-) mice but not in males. Despite markedly reduced BDNF levels in
      BDNF(+/-) mice and double mutants, ERK1 activation was unchanged in the female
      mice. In contrast, ERK2 activation was significantly elevated in the VHP of
      female BDNF(+/-) mice and double mutants. Given the greater vulnerability of
      women to develop depression and the role of the VHP in stress responses and
      anxiety-related behaviours, our results may shed more light on sex differences in
      depression and other psychiatric disorders with BDNF and 5-HT1A receptor
      dysfunction.

PMID- 22464184
TI  - The effect of chronic intermittent ethanol exposure on spatial memory in
      adolescent rats: the dissociation of metabolic and cognitive tolerances.
AB  - Using a rapid chronic intermittent ethanol (CIE) vapor exposure paradigm, we
      demonstrate the dissociability of metabolic tolerance from cognitive tolerance in
      adolescent rats. Adolescent rats were trained to spatially navigate in the Morris
      Water Maze and then exposed to CIE vapor or air 16 h a day for 4 days. After a
      final 28 h withdrawal, all rats received a saline or ethanol challenge, followed
      by a test of spatial memory 30 min after administration. Results indicate that
      CIE vapor exposure did not significantly impair adolescent spatial memory.
      Although CIE-exposed rats developed metabolic tolerance to a subsequent ethanol
      administration, CIE exposure did not alter dose-dependent ethanol-induced spatial
      memory impairments. These data indicate that metabolic ethanol tolerance can be
      distinguished from cognitive ethanol tolerance during adolescence and suggest
      that blood alcohol levels alone do not fully explain ethanol-induced spatial
      memory impairments.

PMID- 22464181
TI  - Amygdala hyperactivity and tonotopic shift after salicylate exposure.
AB  - The amygdala, important in forming and storing memories of aversive events, is
      believed to play a major role in debilitating tinnitus and hyperacusis. To
      explore this hypothesis, we recorded from the lateral amygdala (LA) and auditory
      cortex (AC) before and after treating rats with a dose of salicylate that induces
      tinnitus and hyperacusis-like behavior. Salicylate unexpectedly increased the
      amplitude of the local field potential (LFP) in the LA making it hyperactive to
      sounds>=60 dB SPL. Frequency receptive fields (FRFs) of multiunit (MU) clusters
      in the LA were also dramatically altered by salicylate. Neuronal activity at
      frequencies below 10 kHz and above 20 kHz was depressed at low intensities, but
      was greatly enhanced for stimuli between 10 and 20 kHz (frequencies near the
      pitch of the salicylate-induced tinnitus in the rat). These frequency-dependent
      changes caused the FRF of many LA neurons to migrate towards 10-20 kHz thereby
      amplifying activity from this region. To determine if salicylate-induced changes
      restricted to the LA would remotely affect neural activity in the AC, we used a
      micropipette to infuse salicylate (20 MUl, 2.8 mM) into the amygdala. Local
      delivery of salicylate to the amygdala significantly increased the amplitude of
      the LFP recorded in the AC and selectively enhanced the neuronal activity of AC
      neurons at the mid-frequencies (10-20 kHz), frequencies associated with the
      tinnitus pitch. Taken together, these results indicate that systemic salicylate
      treatment can induce hyperactivity and tonotopic shift in the amygdala and
      infusion of salicylate into the amygdala can profoundly enhance sound-evoked
      activity in AC, changes likely to increase the perception and emotional salience
      of tinnitus and loud sounds. This article is part of a Special Issue entitled:
      Tinnitus Neuroscience.

PMID- 22464185
TI  - Evaluation of the effectiveness of intrauterine treatment with
      formosulphathiazole of clinical endometritis in postpartum dairy cows.
AB  - In cattle, elimination of bacterial contamination from the uterine lumen after
      parturition is often delayed or compromised, and pathogenic bacteria can persist,
      causing uterine disease and infertility. The aim of this study was to compare the
      clinical and bacteriologic recovery following a single intrauterine
      administration of formosulphatiazole, cephapirin or placebo in cows with clinical
      endometritis. Cows (n = 80), no less than 28 days postpartum, with clinical
      endometritis were enrolled in the study. Endometritis was diagnosed by a complete
      reproductive examination, including rectal palpation, ultrasonography,
      vaginoscopy and uterine swab. All cows were randomly assigned to receive one of
      three intrauterine treatments (T0): 2500 mg of formosulphatiazole (Group A); 500
      mg of cephapirin (Group B); placebo (4250 mg of propylene glycol; Group C). Cows
      were examined at the first estrus after treatment or no more than 30 days after
      (T1). Bacteria isolated were E. coli, A. pyogenes, Pasteurella spp. and
      Streptococcus spp. After treatment, in Group A and B only 6/30 (20.0%) and 6/24
      (25.0%) cows showed a positive bacteriologic culture (P > 0.05), while in Group C
      the number of positive animals was significantly higher (19/26; 73.1%; P < 0.05).
      At T0, total clinical scores were similar between the three groups (Group A: 5.84
      +/- 1.07; Group B: 5.91 +/- 1.0; Group C: 5.62 +/- 1.17; P > 0.05) and indicative
      of clinical endometritis. At T1, endometritis scores were significantly lower
      than those reported before uterine infusion (P < 0.05); however, Group A and B
      score, 0.4 +/- 0.9 and 1.0 +/- 2.1, respectively, correspond to no and slight
      endometritis, while animals in Group C reported a total endometritis score
      significantly higher (4.6 +/- 3.5; P < 0.05) corresponding to endometritis. In
      the present study, a commercial formosulphatiazole preparation was as effective
      as cephapirin and more effective than placebo for the treatment of clinical
      endometritis.

PMID- 22464186
TI  - Amounts of an estrogen receptor beta isoform increased in the theca of
      preovulatory follicles of sheep.
AB  - Determination of the specific roles of the estrogen receptor (ER) forms in
      reproductive processes of different species remains incomplete. In the present
      experiment, cellular localization and changes in relative amounts of the ERalpha
      and ERbeta in late developing ovarian follicles, oviduct, and uterus were
      determined during the follicular phase of the estrous cycle in sheep. Ewes in mid
      luteal phase were treated with prostaglandin F(2alpha) (PG) to induce luteolysis
      and control the onset of the follicular phase. The oviducts, uterus, and the
      ovaries were collected at 0 (ewes not treated with PG), 4, 18, and 36 h after PG
      treatment (early, mid, and late follicular phase, respectively) and processed to
      evaluate the ERs using immunohistochemical (IHC) procedures. The ERalpha was
      localized to nuclei of granulosa cells of late developing follicles and most
      cells of the oviduct and uterus. The ERbeta was detected only in ovarian
      follicles using two antibodies directed to different regions of the ERbeta.
      Western immunoblotting demonstrated that the antibody directed against the N
      terminal region of the ERbeta detected one isoform (approximately 53 kDa) whereas
      the antibody directed against the C-terminus detected two ERbeta isoforms
      (approximately 53 kDa and 59 kDa). Western and IHC results combined indicated
      presence of the 59 kDa ERbeta in granulosa cells and the 53 kDa ERbeta in both
      granulosa and theca cells. Relative amounts (immunostaining intensity) of the
      ERalpha increased (P<.05) in granulosa cells of preovulatory follicles and in the
      isthmian muscularis of the oviduct at the late follicular phase. Amounts of the
      ERalpha in the mucosal epithelium of the oviductal regions (isthmus, ampulla, and
      infundibulum), and in various uterine cell types (glandular and luminal
      epithelia, endometrial stromal cells, and myometrium) did not change (P>.05)
      throughout the follicular phase. A major increase (four-fold) in expression of
      the 53 kDa ERbeta in the theca and a less pronounced increase in the granulosa
      occurred at the late follicular phase. The ERalpha is broadly expressed in
      reproductive organs of sheep and is upregulated only in few cell types during the
      late follicular phase. Immunoreactive ERbeta was detected only in the ovary.
      Important estrogen actions in theca cells during preovulatory follicular
      development likely occur in association with a major increase in expression of an
      ERbeta isoform.

PMID- 22464187
TI  - Cold hyperalgesia as a prognostic factor in whiplash associated disorders: a
      systematic review.
AB  - OBJECTIVE: To review and critically evaluate the existing literature for the
      prognostic value of cold hyperalgesia in Whiplash Associated Disorders (WAD).
      METHODS: Embase, PsycINFO, and Medline databases were systematically searched
      (from inception to 20th September 2011) for prospective studies investigating a
      prognostic ability for cold hyperalgesia in WAD. Reference lists and lead authors
      were cross-referenced. Two independent reviewers selected studies, and consensus
      was achieved via a third reviewer. The risk of bias in identified studies was
      systematically evaluated by two reviewers using previously published guidance.
      The influences of seven potential covariates of cold hyperalgesia were
      considered. Quantitative synthesis was planned and homogeneity assessed. A
      modified Grades of Recommendation, Assessment, Development, and Evaluation
      (GRADE) approach was used to qualitatively assess trials. RESULTS: The review
      screened 445 abstracts, from these 20 full text studies were retrieved and
      assessed for eligibility. Six prospective studies on four cohorts were identified
      and reviewed. Findings from all four cohorts supported cold hyperalgesia as a
      prognostic factor in WAD. CONCLUSIONS: There is moderate evidence supporting cold
      hyperalgesia as a prognostic factor for long-term pain and disability outcome in
      WAD. Further validation of the strength of this relationship and the influence of
      covariates are required. The mechanism for this relationship is unknown.

PMID- 22464188
TI  - Description, reliability and validity of a novel method to measure carpal tunnel
      pressure in patients with carpal tunnel syndrome.
AB  - Elevated carpal tunnel pressure is an important pathomechanism in carpal tunnel
      syndrome (CTS). Several invasive methods have been described for direct
      measurement of carpal tunnel pressure, but all have two important limitations.
      The pressure gauge requires sterilisation between uses, which makes time
      efficient data collection logistically cumbersome, and more importantly, the
      reliability of carpal tunnel pressure measurements has not been evaluated for any
      of the methods in use. This technical note describes a new method to measure
      carpal tunnel pressure using inexpensive, disposable pressure sensors and reports
      the within and between session reliability of the pressure recordings in five
      different wrist positions and during typing and computer mouse operation.
      Intraclass correlation coefficients (ICC[3,1]) were calculated for recordings
      within one session for healthy participants (n = 7) and patients with CTS (n =
      5), and for recordings between two sessions for patients with CTS (n = 5).
      Overall, the reliability was high. With the exception of two coefficients, the
      reliability of the recordings at different wrist angles varied from 0.63 to 0.99.
      Reliability for typing and mouse operation ranged from 0.86 to 0.99. The new
      method described in this report is inexpensive and reliable, and data collection
      can be applied more efficiently as off-site sterilisation of equipment is not
      required. These advances are likely to promote future research into carpal tunnel
      pressure, such as investigation of the therapeutic mechanisms of various
      conservative treatment modalities that are believed to reduce elevated carpal
      tunnel pressure.

PMID- 22464189
TI  - Organochlorine pesticides in soil under irrigated cotton farming systems in
      Vertisols of the Namoi Valley, north-western New South Wales, Australia.
AB  - Organochlorine pesticides (OCPs) such as DDT and DDE have been detected in the
      surface 0.2m of Vertisols in the lower Namoi Valley of north western New South
      Wales, Australia even though they have not been applied to crops since 1982.
      However, their presence in the deeper soil horizons has not been investigated.
      The objective of this study was to determine if OCPs were present to a depth of
      1.2m in Vertisols under irrigated cotton farming systems in the lower Namoi
      Valley of New South Wales. Soil was sampled from the 0-1.2m depths in three
      sites, viz. the Australian Cotton Research Institute, ACRI, near Narrabri (149
      degrees 36'E, 30 degrees 12'S), and two cotton farms near Wee Waa (149 degrees
      27'E, 30 degrees 13'S) and Merah North (149 degrees 18'E, 30 degrees 12'S) in
      northern New South Wales, Australia. The OCPs detected and their metabolites were
      alpha-endosulfan, beta-endosulfan, endosulfan sulphate, DDD, DDE, DDT and endrin.
      The metabolite DDE, a breakdown product of DDT, was the most persistent OCP in
      all depths analysed. Endosulfan sulphate was the second most persistent followed
      by endrin>alpha-endosulfan>beta-endosulfan>DDT and DDD. DDT was sprayed
      extensively in the lower Namoi Valley up to the early 1980s and may explain the
      persistence of DDE in the majority of soil samples. Dicofol and Dieldrin, two
      OCPs previously undocumented in Vertisols were also detected. The movement of
      OCPs into the subsoil of Vertisols may occur when irrigation or rain transports
      soil colloids and organic matter via preferential flow systems into the deeper
      layers of a soil profile. Persistence of OCPs was closely correlated to soil
      organic carbon concentrations. The persistence in soil of OCP's applied to cotton
      crops grown more than two decades ago suggests that they could enter the food
      chain. Their presence at depths of 1.2m suggests that they could move into
      groundwater that may eventually be used for domestic and stock consumption.

PMID- 22464190
TI  - Epigenetic inactivation and subsequent heterochromatinization of a centromere
      stabilize dicentric chromosomes.
AB  - BACKGROUND: The kinetochore is a multiprotein complex that forms on a chromosomal
      locus designated as the centromere, which links the chromosome to the spindle
      during mitosis and meiosis. Most eukaryotes, with the exception of holocentric
      species, have a single distinct centromere per chromosome, and the presence of
      multiple centromeres on a single chromosome is predicted to cause breakage and/or
      loss of that chromosome. However, some stably maintained non-Robertsonian
      translocated chromosomes have been reported, suggesting that the excessive
      centromeres are inactivated by an as yet undetermined mechanism. RESULTS: We have
      developed systems to generate dicentric chromosomes containing two centromeres by
      fusing two chromosomes in fission yeast. Although the majority of cells harboring
      the artificial dicentric chromosome are arrested with elongated cell morphology
      in a manner dependent on the DNA structure checkpoint genes, a portion of the
      cells survive by converting the dicentric chromosome into a stable functional
      monocentric chromosome; either centromere was inactivated epigenetically or by
      DNA rearrangement. Mutations compromising kinetochore formation increased the
      frequency of epigenetic centromere inactivation. The inactivated centromere is
      occupied by heterochromatin and frequently reactivated in heterochromatin- or
      histone deacetylase-deficient mutants. CONCLUSIONS: Chromosomes with multiple
      centromeres are stabilized by epigenetic centromere inactivation, which is
      initiated by kinetochore disassembly. Consequent heterochromatinization and
      histone deacetylation expanding from pericentric repeats to the central domain
      prevent reactivation of the inactivated centromere.

PMID- 22464191
TI  - Uridylation of miRNAs by hen1 suppressor1 in Arabidopsis.
AB  - HEN1-mediated 2'-O-methylation has been shown to be a key mechanism to protect
      plant microRNAs (miRNAs) and small interfering RNAs (siRNAs) as well as animal
      piwi-interacting RNAs (piRNAs) from degradation and 3' terminal uridylation [1
      8]. However, enzymes uridylating unmethylated miRNAs, siRNAs, or piRNAs in hen1
      are unknown. In this study, a genetic screen identified a second-site mutation
      hen1 suppressor1-2 (heso1-2) that partially suppresses the morphological
      phenotypes of the hypomorphic hen1-2 allele and the null hen1-1 allele in
      Arabidopsis. HESO1 encodes a terminal nucleotidyl transferase that prefers to add
      untemplated uridine to the 3' end of RNA, which is completely abolished by 2'-O
      methylation. heso1-2 affects the profile of u-tailed miRNAs and siRNAs and
      increases the abundance of truncated and/or normal sized ones in hen1, which
      often results in increased total amount of miRNAs and siRNAs in hen1. In
      contrast, overexpressing HESO1 in hen1-2 causes more severe morphological defects
      and less accumulation of miRNAs. These results demonstrate that HESO1 is an
      enzyme uridylating unmethylated miRNAs and siRNAs in hen1. These observations
      also suggest that uridylation may destabilize unmethylated miRNAs through an
      unknown mechanism and compete with 3'-to-5' exoribonuclease activities in hen1.
      This study shall have implications on piRNA uridylation in hen1 in animals.

PMID- 22464192
TI  - Ribonucleotide reductase activity is coupled to DNA synthesis via proliferating
      cell nuclear antigen.
AB  - Synthesis of deoxynucleoside triphosphates (dNTPs) is required for both DNA
      replication and DNA repair and is catalyzed by ribonucleotide reductases (RNR),
      which convert ribonucleotides to their deoxy forms [1, 2]. Maintaining the
      correct levels of dNTPs for DNA synthesis is important for minimizing the
      mutation rate [3-7], and this is achieved by tight regulation of RNR [2, 8, 9].
      In fission yeast, RNR is regulated in part by a small protein inhibitor, Spd1,
      which is degraded in S phase and after DNA damage to allow upregulation of dNTP
      supply [10-12]. Spd1 degradation is mediated by the activity of the CRL4(Cdt2)
      ubiquitin ligase complex [5, 13, 14]. This has been reported to be dependent on
      modulation of Cdt2 levels, which are cell cycle regulated, peaking in S phase,
      and which also increase after DNA damage in a checkpoint-dependent manner [7,
      13]. We show here that Cdt2 level fluctuations are not sufficient to regulate
      Spd1 proteolysis and that the key step in this event is the interaction of Spd1
      with the polymerase processivity factor proliferating cell nuclear antigen
      (PCNA), complexed onto DNA. This mechanism thus provides a direct link between
      DNA synthesis and RNR regulation.

PMID- 22464193
TI  - Swarming generates rebel workers in honeybees.
AB  - According to kin selection theory, the colony kin structure of eusocial insects
      motivates workers' altruistic behaviors and therefore their sterility or
      restricted reproduction [1]. Indeed, theory and cross-species comparison confirm
      that workers engage in their own reproduction depending on relatedness among
      colony members [2, 3]. We show that in a honeybee colony, the workers switch from
      their typical altruistic role to a more selfish one if at their larval stage
      there are environmental cues of an upcoming decline in intracolony relatedness.
      This happens inevitably when a colony multiplies by swarming and replaces the
      mother queen with her daughter, because the mother queen's workers are faced with
      rearing the sister queen's offspring related to them half as much as between
      sisters. Workers developing from the mother queen's eggs immediately after
      swarming, in a temporarily queenless colony, had more ovarioles in their ovaries
      and less-developed hypopharyngeal glands producing brood food than control
      workers reared in queenright conditions. These "rebel" workers were more engaged
      in laying their own male-determined eggs than in rearing offspring, whether or
      not the sister queen was present in the colony. The finding of this previously
      unknown rebel strategy confirms that kin selection shapes both cooperation and
      conflict in honeybee societies.

PMID- 22464194
TI  - The Arabidopsis nucleotidyl transferase HESO1 uridylates unmethylated small RNAs
      to trigger their degradation.
AB  - MicroRNAs (miRNAs), small interfering RNAs (siRNAs), and piwi-interacting RNAs
      (piRNAs) impact numerous biological processes in eukaryotes. In addition to
      biogenesis, turnover contributes to the steady-state levels of small RNAs. One
      major factor that stabilizes miRNAs and siRNAs in plants as well as siRNAs and
      piRNAs in animals is 2'-O-methylation on the 3' terminal ribose by the
      methyltransferase HUA ENHANCER1 (HEN1) [1-6]. Genetic studies with Arabidopsis,
      Drosophila, and zebrafish hen1 mutants show that 2'-O-methylation protects small
      RNAs from 3'-to-5' truncation and 3' uridylation, the addition of nontemplated
      nucleotides, predominantly uridine [2, 7, 8]. Uridylation is a widespread
      phenomenon that is not restricted to small RNAs in hen1 mutants and is often
      associated with their reduced accumulation ([7, 9, 10]; reviewed in [11]). The
      enzymes responsible for 3' uridylation of small RNAs when they lack methylation
      in plants or animals have remained elusive. Here, we identify the Arabidopsis
      HEN1 SUPPRESSOR1 (HESO1) gene as responsible for small RNA uridylation in hen1
      mutants. HESO1 exhibits terminal nucleotidyl transferase activity, prefers
      uridine as the substrate nucleotide, and is completely inhibited by 2'-O
      methylation. We show that uridylation leads to miRNA degradation, and the
      degradation is most likely through an enzyme that is distinct from that causing
      the 3' truncation in hen1 mutants.

PMID- 22464195
TI  - [Validation in Spain of the quality of life questionnaire PROSQOLI in patients
      with advanced prostate cancer].
AB  - OBJECTIVES: Validation of the PROSQOLI questionnaire adapted to Spanish, pursing
      an instrument to evaluate, in the common clinical practice, the quality of life
      in patients with locally advanced or disseminated prostate cancer in our country.
      MATERIAL AND METHODS: A cross-sectional prospective study was designed in 750
      patients (150 centers) with disseminated or locally advanced prostate cancer (TNM
      criterion) who came to the scheduled check-up. Socio-demographic and clinical
      data of the participants were collected. The subjects filled out the PROSQOLI and
      EQ-5D questionnaires. The analysis included 561 cases that met the selection
      criteria. The psychometric characteristics (feasibility, validity and
      reliability) of the adapted PROSQOLI questionnaire were studied. RESULTS: Mean
      age was 73.63 (7.59) years. A total of 72.01% of the participants had locally
      advanced disease. In 28.16%, the primary treatment was radiotherapy, in 12.30% it
      was prostatectomy. A total of 83.48% received hormone treatment. The mean for
      each scale of the PROSQOLI questionnaire varied from 68.86 to 74.51. The
      percentage of no response was less than 3% for each scale. The percentage of
      subjects with minimum score in any scale was negligible, and the maximum score
      did not surpass 5%. Mean time to fill out the questionnaire was 109.42 (101.00)
      seconds. Cronbach's alpha coefficient was 0.937 and the total item correlation
      was superior to 0.7 for all the items. Correlations with the EQ-5D questionnaire
      were moderate. Scores on the questionnaire were associated to all the parameters
      studied related to the disease. CONCLUSIONS: The adapted questionnaire has
      adequate psychometric properties for its use in research and in the clinical
      practice.

PMID- 22464196
TI  - [RNASEL study of genetics of prostate cancer and its relation to clinical
      staging].
AB  - OBJECTIVES: This study has aimed to find a possible genetic relationship between
      sporadic prostate cancers. An attempt is made to establish population subgroups
      in patients based on the genotype found and the aggressiveness of the cancer.
      MATERIAL AND METHODS: A total of 231 patients with sporadic prostate cancer and
      68 controls were selected. The subjects were selected by an urologist using
      clinical parameters such as PSA level and Gleason score. Both groups (patients
      and controls) were genotyped in RNASEL gene by sequencing the exons 1 and 3.
      RESULTS: Statistically significant differences were found between controls and
      patients in some of the genotyped regions of the RNASEL gene (I97L, D541E and
      R462Q). CONCLUSIONS: Thanks to the genetic profile in some regions of the genoma,
      such as the RNASEL gene, together with the combination of the clinical and
      environmental parameters, we can suggest a care and more personalized follow-up
      of each patient.

PMID- 22464199
TI  - Almanac 2011: valvular heart disease. The national society journals present
      selected research that has driven recent advances in clinical cardiology.

PMID- 22464198
TI  - Three-dimensional subharmonic ultrasound imaging in vitro and in vivo.
AB  - RATIONALE AND OBJECTIVES: Although contrast-enhanced ultrasound imaging
      techniques such as harmonic imaging (HI) have evolved to reduce tissue signals
      using the nonlinear properties of the contrast agent, levels of background
      suppression have been mixed. Subharmonic imaging (SHI) offers near complete
      tissue suppression by centering the receive bandwidth at half the transmitting
      frequency. The aims of this study were to demonstrate the feasibility of three
      dimensional (3D) SHI and to compare it to 3D HI. MATERIALS AND METHODS: Three
      dimensional HI and SHI were implemented on a Logiq 9 ultrasound scanner with a
      4D10L probe. Four-cycle SHI was implemented to transmit at 5.8 MHz and receive at
      2.9 MHz, while two-cycle HI was implemented to transmit at 5 MHz and receive at
      10 MHz. The ultrasound contrast agent Definity was imaged within a flow phantom
      and the lower pole of two canine kidneys in both HI and SHI modes. Contrast-to
      tissue ratios and rendered images were compared offline. RESULTS: SHI resulted in
      significant improvement in contrast-to-tissue ratios relative to HI both in vitro
      (12.11 +/- 0.52 vs 2.67 +/- 0.77, P< .001) and in vivo (5.74 +/- 1.92 vs 2.40 +/-
      0.48, P = .04). Rendered 3D subharmonic images provided better tissue suppression
      and a greater overall view of vessels in a flow phantom and canine renal
      vasculature. CONCLUSIONS: The successful implementation of SHI in 3D allows
      imaging of vascular networks over a heterogeneous sample volume and should
      improve future diagnostic accuracy. Additionally, 3D SHI provides improved
      contrast-to-tissue ratios relative to 3D HI.

PMID- 22464200
TI  - Examining the course of hallucinatory experiences in children and adolescents: a
      systematic review.
AB  - BACKGROUND: Childhood and adolescence represent the periods during which
      hallucinatory experiences occur at the greatest prevalence, and also constitute a
      critical window of vulnerability for the pathogenesis of psychotic disorders. The
      longitudinal course of hallucinatory experiences during late childhood and
      adolescence, as well as their relationship to psychotic disorders, has never been
      the subject of review. METHODS: We followed the PRISMA guidelines for conducting
      systematic reviews and combined the use of electronic and manual systematic
      search methods. Data were extracted upon pre-defined requested items and were
      analyzed using several epidemiological measures. The interpretation of the
      results was conducted in relation to the study design variables. RESULTS: A total
      of 11 datasets (6 epidemiological and 5 clinical) were reviewed. The baseline
      prevalence of hallucinatory experiences ranged from 4.9% to 9%. Discontinuation
      occurred in between 58.7% and 94.5% of the cases, and person-year discontinuation
      rates ranged from 3% to 40.7% and appeared to be related to the duration of
      follow-up. Despite low person-year incidence rate, incident cases constituted
      between 27.7% and 83.3% of outcome samples. 2 of 3 studies showed evidence to
      predict transition to psychosis with likelihood ratios of 2.5 and 6.6.
      CONCLUSIONS: Hallucinatory experiences are a common experience during childhood
      and adolescence. A review of the current literature suggests that there is a
      considerable turnover of incident-discontinuing cases and that most cases
      discontinue in the short term. A subset of the cases was at risk for persistence
      or transition to psychosis, probably related to indicators of severity of the
      hallucinatory experience.

PMID- 22464201
TI  - Balance of hip and trunk muscle activity is associated with increased anterior
      pelvic tilt during prone hip extension.
AB  - Prone hip extension has been used as a self-perturbation task to test the
      stability of the lumbopelvic region. However, the relationship between
      recruitment patterns in the hip and trunk muscles and lumbopelvic kinematics
      remains unknown. The present study aimed to examine if the balance of hip and
      trunk muscle activities are related to pelvic motion and low back muscle activity
      during prone hip extension. Sixteen healthy participants performed prone hip
      extension from 30 degrees  of hip flexion to 10 degrees  of hip extension.
      Surface electromyography (of the gluteus maximus, semitendinosus, rectus femoris,
      tensor fasciae latae, multifidus, and erector spinae) and pelvic kinematic
      measurements were collected. Results showed that increased activity of the hip
      flexor (tensor fasciae latae) relative to that of hip extensors (gluteus maximus
      and semitendinosus) was significantly associated with increased anterior pelvic
      tilt during hip extension (r=0.52). Increased anterior pelvic tilt was also
      significantly related to the delayed onset timing of the contralateral and
      ipsilateral multifidus (r=0.57, r=0.53) and contralateral erector spinae
      (r=0.63). Additionally, the decrease of the gluteus maximus activity relative to
      the semitendinosus was significantly related to increased muscle activity of the
      ipsilateral erector spinae (r=-0.57). These results indicate that imbalance
      between the agonist and antagonist hip muscles and delayed trunk muscle onset
      would increase motion in the lumbopelvic region.

PMID- 22464202
TI  - Proposal of an environmental performance index to assess solid waste treatment
      technologies.
AB  - Although the concern with sustainable development and environment protection has
      considerably grown in the last years it is noted that the majority of decision
      making models and tools are still either excessively tied to economic aspects or
      geared to the production process. Moreover, existing models focus on the priority
      steps of solid waste management, beyond waste energy recovery and disposal. So,
      in order to help the lack of models and tools aiming at the waste treatment and
      final disposal, a new concept is proposed: the Cleaner Treatment, which is based
      on the Cleaner Production principles. This paper focuses on the development and
      validation of the Cleaner Treatment Index (CTI), to assess environmental
      performance of waste treatment technologies based on the Cleaner Treatment
      concept. The index is formed by aggregation (summation or product) of several
      indicators that consists in operational parameters. The weights of the indicator
      were established by Delphi Method and Brazilian Environmental Laws. In addition,
      sensitivity analyses were carried out comparing both aggregation methods.
      Finally, index validation was carried out by applying the CTI to 10 waste-to
      energy plants data. From sensitivity analysis and validation results it is
      possible to infer that summation model is the most suitable aggregation method.
      For summation method, CTI results were superior to 0.5 (in a scale from 0 to 1)
      for most facilities evaluated. So, this study demonstrates that CTI is a simple
      and robust tool to assess and compare the environmental performance of different
      treatment plants being an excellent quantitative tool to support Cleaner
      Treatment implementation.

PMID- 22464203
TI  - Transient osteoporosis of pregnancy.
AB  - Transient osteoporosis of pregnancy (TOP) is a rare yet perhaps under-reported
      condition that has affected otherwise healthy pregnancies throughout the world.
      The condition presents suddenly in the third trimester of a usually uneventful
      pregnancy and progressively immobilizes the mother. Radiographic studies detect
      drastic loss of bone mass, elevated rates of turnover in the bone, and oedema in
      the affected portion. Weakness of the bone can lead to fractures during delivery
      and other complications for the mother. Then, within weeks of labour, symptoms
      and radiological findings resolve. Aetiology is currently unknown, although
      neural, vascular, haematological, endocrine, nutrient-deficiency, and other
      etiologies have been proposed. Several treatments have also been explored,
      including simple bed rest, steroids, bisphosphonates, calcitonin, induced
      termination of pregnancy, and surgical intervention. The orthopedist plays an
      essential role in monitoring the condition (and potential complications) as well
      as ensuring satisfactory outcomes for both the mother and newborn.

PMID- 22464204
TI  - Expression of platelet-derived growth factor-B mRNA during vaginal vs. dermal
      incisional wound healing in the rabbit.
AB  - OBJECTIVE: The outcome of pelvic reconstructive surgery is largely dependent on
      the vaginal wound healing process, but this process has not yet been fully
      elucidated. Platelet-derived growth factor (PDGF) is an important mediator of the
      wound healing process in cutaneous tissue. We sought to compare PDGF-B mRNA
      expression in vaginal versus cutaneous incisional wound healing in a rabbit
      model. STUDY DESIGN: Bilateral 6 mm full-thickness circular segments were excised
      from the vagina and abdominal skin in 36 New Zealand-White female rabbits.
      Animals were euthanized sequentially before, on the day of and 4, 7, 10, 14, 21,
      28 and 35 days after wounding. Their wounds were evaluated for surface area and
      PDGF-B mRNA expression using real time PCR. RESULTS: In both tissues PDGF-B mRNA
      expression increased constantly after wounding, reaching peak levels on day 10,
      and declined immediately thereafter, reaching minimal values on day 21. In both
      tissues, the expression of PDGF-B mRNA significantly correlated with the wound
      closure rate. CONCLUSION: PDGF-B mRNA expression significantly correlates with
      incisional vaginal and cutaneous wound closure, suggesting that this factor plays
      an important role in the wound healing process of both tissues.

PMID- 22464205
TI  - Management of adult primary vulvar Langerhans cell histiocytosis: review of the
      literature and a case history.
AB  - Primary vulvar Langerhans cell histiocytosis (LCH) is extremely rare and there
      are no standard treatment options. This review of the published literature with a
      case report aimed to clarify the optimal treatment for patients with this
      condition. Medline and PubMed were searched and all cases of primary vulvar LCH
      reported as single case reports or small case series were reviewed. A patient
      with vulvar LCH treated in this department is also reported. Twenty-seven cases,
      including the reported case, were reviewed. First-line treatments included
      surgery, radiotherapy, chemotherapy, thalidomide and local treatment. The mean
      follow-up time was 21.1+/-17.7 months. Although no patient died from the disease,
      recurrence rates were high (62%) and the mean time to relapse was 10.9+/-11.8
      months (range 1-36 months). Treatment with thalidomide was successful, resulting
      in long-lasting remission. Disease recurrence is likely after surgery and or
      radiotherapy, and these treatments together with chemotherapy affect the
      patient's wellbeing adversely. Although definitive conclusions await further
      work, thalidomide has minimal adverse effects, is easy to administer and should
      be considered as a first-line treatment or as maintenance therapy in some
      patients.

PMID- 22464206
TI  - Possible factors for altered energy balance across the menstrual cycle: a closer
      look at the severity of PMS, reward driven behaviors and leptin variations.
AB  - This paper reviews the literature on the variations in energy intake (EI), energy
      expenditure (EE) and the factors which may affect the fluctuations in EI across
      the menstrual cycle. While no significant changes in body weight and body fat
      percentage have been noted across the cycle, increases in EI and EE have been
      well documented during the luteal phase in lean women. The occurrence and
      severity of the premenstrual syndrome (PMS) and food reinforcement are suggested
      to affect EI. It is not known, however, whether food reinforcement may affect EI
      across the menstrual cycle. These factors may also affect overweight/obese women
      differently than normal-weight women at times during which women may be more
      prone to episodes of overeating during the menstrual cycle. Certain studies have
      also noted fluctuations in leptin levels across the menstrual cycle, while others
      have not. It has also been suggested that variations in leptin levels may affect
      the rewarding value of food in order to maintain proper body weight and adiposity
      level. We emphasize that future studies should evaluate the variations in energy
      balance across the cycle in overweight/obese women, as well as the strength of
      the relationships between food reinforcement and the severity of PMS with energy
      and macronutrient intakes.

PMID- 22464207
TI  - Polycystic ovary syndrome and diabetes screening: a survey of gynecologists and
      reproductive endocrinologists.
AB  - OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are at high risk of
      developing type 2 diabetes mellitus. The purpose of this study was to assess self
      reported methods used by specialists in obstetrics and gynecology (OB/GYN) and in
      reproductive endocrinology and infertility (REI) to screen for type 2 diabetes in
      women with PCOS. STUDY DESIGN: We analyzed responses to a web-based survey of
      from 123 OB/GYN and 223 REI physician members of the American Society for
      Reproductive Medicine. RESULTS: Initial diabetes screening of all women with PCOS
      was performed by fewer OB/GYNs (57%) than REIs (71%). Approximately 1/3 of both
      groups reported initial screening only for those with additional risk factors,
      and 3% reported no screening. Re-screening for diabetes was reportedly performed
      by similar numbers of OB/GYNs (49%) and REIs (53%). Re-screening was reportedly
      not performed by the remaining 51% of OB/GYNs and 47% of REIs. For initial
      screening, the 2h glucose tolerance test (GTT) was reportedly used by fewer
      OB/GYNs than REIs (59% vs 72%), fasting plasma glucose (FPG) by more OB/GYNs (22%
      vs 8%), and hemoglobin A1c (HbA1c) by a similar number (19% vs 20%). For re
      screening, GTT was reportedly used by a similar proportion of OB/GYNs and REIs
      (27% vs 32%), FPG was used more by OB/GYNs (43% vs 23%), and HbA1c was used less
      (30% vs 45%). CONCLUSIONS: Not all OB/GYN and REI respondents followed diabetes
      screening guidelines for women with PCOS. Screening rates for women with PCOS
      might be increased by continued educational efforts concerning their high risk
      for diabetes, and by the recent recommendation to use HbA1c for diabetes
      screening in high-risk populations.

PMID- 22464208
TI  - Persistent pelvic pain following transvaginal mesh surgery: a cause for mesh
      removal.
AB  - OBJECTIVE: Persistent pelvic pain after vaginal mesh surgery is an uncommon but
      serious complication that greatly affects women's quality of life. Our aim was to
      evaluate various procedures for mesh removal performed at a tertiary referral
      center in cases of persistent pelvic pain, and to evaluate the ensuing
      complications and outcomes. STUDY DESIGN: A retrospective study was conducted at
      the University Hospital of Caen, France, including all patients treated for
      removal or section of vaginal mesh due to pelvic pain as a primary cause, between
      January 2004 and September 2009. RESULTS: Ten patients met the inclusion
      criteria. Patients were diagnosed between 10 months and 3 years after their
      primary operation. Eight cases followed suburethral sling procedures and two
      followed mesh surgery for pelvic organ prolapse. Patients presented with
      obturator neuralgia (6), pudendal neuralgia (2), dyspareunia (1), and non
      specific pain (1). The surgical treatment to release the mesh included: three
      cases of extra-peritoneal laparoscopy, four cases of complete vaginal mesh
      removal, one case of partial mesh removal and two cases of section of the
      suburethral sling. In all patients with obturator neuralgia, symptoms were
      resolved or improved, whereas in both cases of pudendal neuralgia the symptoms
      continued. There were no intra-operative complications. Post-operative Retzius
      hematoma was observed in one patient after laparoscopy. CONCLUSIONS: Mesh removal
      in a tertiary center is a safe procedure, necessary in some cases of persistent
      pelvic pain. Obturator neuralgia seems to be easier to treat than pudendal
      neuralgia. Early diagnosis is the key to success in prevention of chronic
      disease.

PMID- 22464209
TI  - Injection of embryo culture supernatant to the endometrial cavity does not affect
      outcomes in IVF/ICSI or oocyte donation cycles: a randomized clinical trial.
AB  - OBJECTIVE: To evaluate whether intrauterine injection of embryo culture
      supernatant before embryo transfer has any impact on pregnancy and implantation
      rates. STUDY DESIGN: A total of 400 cycles, of which 200 IVF/ICSI and 200 oocyte
      donor (OD), were randomly assigned to have their uterine cavity injected (group
      I) or not (group II). Primary endpoints to be studied were pregnancy and
      implantation rates. RESULTS: Clinical pregnancy rate per transfer (47.87%, 90/188
      versus 48.45%, 94/194) based on transvaginal scan findings at 7 weeks of
      gestation and implantation rate (25.6% versus 26.5%) were similar in the two
      groups. The day of embryo transfer, day 3 or day 5, did not affect the final
      outcome. CONCLUSION: Injection of embryo culture supernatant into the uterine
      cavity, 30 min before the embryo transfer on either day 3 or 5, neither improves
      nor adversely affects the pregnancy rate in IVF/ICSI or oocyte donation cycles.

PMID- 22464210
TI  - In vitro production of two chitinolytic proteins with an inhibiting effect on the
      insect coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera:
      Curculionidae) and the fungus Hemileia vastatrix the most limiting pests of
      coffee crops.
AB  - Two genes from Streptomyces albidoflavus, one exochitinase (905-bp) and an
      endochitinase (1100-bp) were functionally expressed in Escherichia coli in form
      of a fusion protein with a maltose binding protein (MBP). The goal was to produce
      and test proteins that inhibit both the coffee berry borer insect Hypothenemus
      hampei and the coffee rust fungus Hemileia vastatrix. Both recombinant proteins
      MBP/exochitinase and MBP/endochitinase showed chitinolytic activity. When
      recombinant purified proteins were added to an artificial coffee-based diet for
      the coffee berry borer, MBP/exochitinase at a concentration of 0.5% W/W caused
      delayed growth of larvae and 100% mortality between days 8 and 15, while
      MBP/endochitinase caused 100% mortality at day 35. H. vastatrix urediniospores
      presented total cell wall degradation in their germinative tubes within 18 h of
      exposure to the proteins at enzyme concentrations of 5 and 6 mg ml-1, with
      exochitinase having the greatest effect. The dual deleterious effect of S.
      albidoflavus chitinases on two of the most limiting coffee pests worldwide, the
      coffee borer and the coffee rust, make them potential elements to be incorporated
      in integrated control strategies.

PMID- 22464211
TI  - Effect of endovascular stenting of right ventricle to pulmonary artery conduit
      stenosis in infants with hypoplastic left heart syndrome on stage II outcomes.
AB  - There is growing awareness that the Norwood procedure with the Sano modification
      is prone to early right ventricular to pulmonary artery (RV-PA) conduit stenosis
      resulting in systemic oxygen desaturation, increased interstage morbidity, and
      death. We report our experience with endovascular stent placement for conduit
      stenosis and compare the outcomes at stage II surgery between stented and
      nonstented infants. The medical records of all patients with hypoplastic left
      heart syndrome who received an RV-PA conduit at Norwood palliation from May 2005
      to January 2010 were reviewed. The preoperative anatomy, demographics, operative
      variables, and outcomes pertaining to the Norwood and subsequent stage II
      surgeries were obtained and compared between stented and nonstented infants. The
      pre- and post-stent oxygen saturation, stenosis location, type and number of
      stents implanted, concomitant interventions, procedure-related complications, and
      reinterventions were collected. Of the 66 infants who underwent the Norwood
      procedure with RV-PA conduit modification, 16 (24%) received stents. The anatomy,
      demographics, and outcome variables after the Norwood procedure were similar
      between the stented and nonstented infants. The age at catheterization was 93 +/-
      48 days, and the weight was 4.9 +/- 1.2 kg. The oxygen saturation increased from
      66 +/- 9% before intervention to 82 +/- 6% immediately after stenting (p
      <0.0001). No interstage surgical shunt revisions were performed in either group.
      Age, weight, pre-stage II echocardiographic variables, oxygen saturation, and
      operative and outcome variables, including mortality, were similar between the 2
      groups. In conclusion, endovascular stent placement for RV-PA conduit stenosis
      after the Norwood procedure leads to improved systemic oxygen levels and prevents
      early performance of stage II surgery without compromising stage II outcomes.

PMID- 22464212
TI  - Impact of routine angiographic follow-up after percutaneous coronary intervention
      with drug-eluting stents in the SPIRIT III randomized trial at three years.
AB  - Routine angiographic follow-up after bare-metal stent implantation has been
      associated with an increase in coronary revascularization. The impact of
      angiographic follow-up after drug-eluting stent placement remains poorly
      characterized. The prospective, randomized, single-blinded SPIRIT III trial
      assigned patients to the everolimus-eluting stent or the paclitaxel-eluting stent
      (PES). Major adverse cardiovascular events (cardiac death, myocardial infarction,
      and ischemia-driven target lesion revascularization [ID-TLR]) at 3 years were
      assessed by angiographic versus clinical-only follow-up at 8 months +/- 28 days
      and a landmark survival analysis from 9 months to 3 years. Of 1,002 patients, 564
      patients were assigned to angiographic follow-up at 8 months +/- 28 days and 438
      patients underwent clinical follow-up alone. Three-year major adverse
      cardiovascular event rates were 10.6% in the angiographic group and 12.0% in the
      clinical follow-up group (p = 0.64). Ischemia-driven revascularization increased
      twofold at 9 months, but no difference was noted in ID-TLR for either device. Non
      ID-TLR was significantly higher in patients in the angiographic group (4.5% vs
      1.0%, p = 0.002), a difference resulting from PES (9.1% vs 0.7%, p = 0.0007)
      rather than everolimus-eluting stent (2.2% vs 1.1%, p = 0.36) treatment. The
      landmark analysis showed no significant differences between the angiographic and
      clinical follow-up groups from 9 months to 3 years of major clinical outcomes. In
      conclusion, routine angiographic follow-up in SPIRIT III did not increase rates
      of ID-TLR compared to clinical follow-up alone. Despite higher nonischemia-driven
      revascularization rates with angiographic follow-up of patients with PESs, none
      of the safety end points were adversely affected.

PMID- 22464213
TI  - Resequencing CETP, LIPC and LIPG genes in Thai subjects with
      hyperalphalipoproteinemia.
AB  - Genetic factors associated with hyperalphalipoproteinemia (HALP; or high levels
      of high-density lipoprotein cholesterol) are incompletely understood. The aim of
      this study was to resequence 3 candidate genes, CETP, LIPC, and LIPG, which
      encode cholesteryl ester transfer protein, hepatic lipase, and endothelial
      lipase, respectively, in Thai subjects with HALP and compare them to
      normolipidemic controls. Sequence variants of CETP, LIPC, and LIPG were
      identified by sequencing exons and exon-intron junctions in 64 subjects with high
      density lipoprotein cholesterol levels >=2.59 mmol/L (100 mg/dl) and compared to
      those of 113 normolipidemic subjects. Two heterozygous frameshift mutations in
      CETP (p.Leu262ProfsX31 and p.Val411ArgfsX6) and two heterozygous missense
      mutations in LIPC (p.Gly141Ser and p.Val173Met) were found. One deletion mutation
      and 3 point mutations in the CETP promoter were also identified. Collectively,
      these rare mutations were found only in the HALP group but not in the control
      group (8% vs 0%, p = 0.0056). One common variant of CETP (p.Asp459Gly) was found
      at a higher frequency in the HALP group (23% vs 4%, p = 0.000074). Altogether,
      rare variants of CETP or LIPC and/or the common CETP p.Asp459Gly variant were
      found in 30% of the HALP group and 4% of the controls (p = 0.0000014). No rare
      variant of LIPG was identified. In conclusion, common and rare genetic variants
      in CETP and LIPC, but not LIPG, were more commonly found in the Thai HALP group,
      which could potentially contribute to high high-density lipoprotein cholesterol
      phenotypes in this population.

PMID- 22464214
TI  - Simpson's paradox and the association between vitamin D deficiency and increased
      heart disease.
AB  - Several recent investigations have highlighted a potential link between vitamin D
      deficiency and increased heart disease. Observational studies suggest
      cardioprotective benefits related to supplementation, but randomized trials
      remain to be conducted. This report adds a caution based on a statistical paradox
      that is rarely mentioned in formal medical training or in common medical
      journals. Insight into this phenomenon, termed Simpson's paradox, may prevent
      clinicians from drawing faulty conclusions about vitamin D deficiency and heart
      disease.

PMID- 22464215
TI  - Incidence and predictors of sudden cardiac arrest in adults with congenital heart
      defects repaired before adult life.
AB  - Many adult survivors of repaired congenital heart disease (CHD) are at premature
      risk of death. Sudden cardiac arrest (SCA) is 1 of the leading causes of death
      but little is known about determinants for SCA in adults with repaired lesions.
      We sought to determine incidence and risk factors for SCA in a study population
      of 936 adults with previously repaired CHD who had completed follow-up at a
      single tertiary center during a mean period of 9 +/- 7 years. Mean age at first
      examination in our institution was 21 +/- 7 years. Diagnostic categories included
      tetralogy of Fallot (216), coarctation of the aorta (157), transposition
      complexes (99), single ventricle (55), and other CHD (409). During a total follow
      up of 8,387 person-years, 22 patients (2.6 per 1,000 person-years) presented with
      SCA. Incidence of SCA varied widely between specific lesions; the highest
      incidence was observed in transposition complexes (10 per 1,000 person-years).
      Independent predictors of SCA were retrospectively identified using multivariate
      Cox proportional hazard modeling. Age at initial examination and severely
      impaired subaortic ventricular systolic function were independent risk factors
      for SCA (severe subaortic ventricular systolic dysfunction, adjusted hazard ratio
      29, 95% confidence interval 11 to 72, p <0.001). SCA occurred in 23% of patients
      with severe subaortic ventricular systolic dysfunction versus 0.7% of patients
      with nonsevere decreased subaortic ventricular function (p <0.001). In
      conclusion, severe subaortic ventricular systolic dysfunction is a dominant
      multivariate predictor of SCA in an unselected population of adult survivors
      after surgery for CHD. Our data support the consideration of primary prevention
      strategies in these patients.

PMID- 22464216
TI  - Comparison of additional versus no additional heparin during therapeutic oral
      anticoagulation in patients undergoing percutaneous coronary intervention.
AB  - Uninterrupted oral anticoagulation (OAC) therapy can be the preferred strategy in
      patients with atrial fibrillation at moderate to high risk of thromboembolism
      undergoing percutaneous coronary intervention (PCI). To evaluate the need for
      additional heparins in addition to therapeutic peri-PCI OAC, we assessed bleeding
      complications and major adverse cardiac and cerebrovascular events in 414
      consecutive patients undergoing PCI during therapeutic (international normalized
      ratio 2 to 3.5) periprocedural OAC. Patients were divided into those with no (n =
      196) and with (n = 218) additional use of periprocedural heparins. No differences
      in major adverse cardiac and cerebrovascular events (4.1% vs 3.2%, p = 0.79) or
      major bleeding (1.0% vs 3.7%, p = 0.11) were detected, but access site
      complications (5.1% vs 11.0%, p = 0.032) were less frequent in those without
      additional heparins. When adjusted for propensity score, patients with additional
      heparins had a higher risk of access site complications (odds ratio 2.6, 95%
      confidence interval 1.1 to 6.1, p = 0.022) without any increased risk of any
      other adverse event. Analysis of 1-to-1 propensity-matched pairs showed a
      significantly higher risk of access site complication in patients receiving
      additional AC (13.1% vs 5.7%, p = 0.049). In conclusion, therapeutic warfarin
      treatment seems to provide sufficient AC for PCI. Additional heparins are not
      needed and may increase access site complications.

PMID- 22464218
TI  - Unsuspected stroke signals: from extravascular blood to vessel lumen.

PMID- 22464217
TI  - Earthquake trauma and causal explanation associating with PTSD and other
      psychiatric disorders among South East Anatolian women.
AB  - INTRODUCTION: The research questions were, first, how exposure to earthquake
      related traumatic events is associated with PTSD and other psychiatric symptoms
      among women after one year of the disaster. Second, how the nature of trauma does
      associate with psychiatric symptoms, and, third, does the causal explanations for
      the trauma moderate the association between traumatic events and psychiatric
      symptoms. METHOD: Participants were 1253 women from South East Anatolian region
      who were interviewed in their homes for their psychosocial needs and mental
      health status. PTSD was assessed by the Post Traumatic Stress Scale (PDS),
      psychiatric symptoms by the Brief Symptom Inventory (BSI), and trauma-exposure
      and explanations by single questions. Results show relatively high prevalence of
      PTSD, 61%. A dose-effect association was found between the number of earthquake
      related traumatic events and PTSD and psychiatric symptoms. The nature of trauma
      was, to some extent, significant in the associations with psychiatric symptoms
      and PTSD. Experiences involving death were comprehensively associated with
      psychiatric symptoms, whereas material losses were not. About a half of the women
      explained the trauma as a will and guidance of the God, 41% as a natural event,
      and 9% blamed human irresponsibility. DISCUSSION: As hypothesized, women who
      blamed other humans for the disaster reported higher levels of depressive,
      somatization and paranoid symptoms than those explaining it as God's will or a
      natural event. Results refuted, however, the hypothesis about the protective role
      of religious explanation in the high exposure to earthquake related trauma.

PMID- 22464219
TI  - Current osteoarthritis treatment, prescribing influences and barriers to
      implementation in primary care.
AB  - AIM: To explore general practitioners' (GPs) management of osteoarthritis (OA).
      BACKGROUND: OA represents a large burden on primary care. Little is known about
      GPs' current management of OA, especially influences on their prescribing quality
      care and the barriers they face while doing so. METHODS: A total of 1006 GPs were
      randomly selected and invited to participate in an online survey on assessment
      and treatment of OA, on factors influencing their management, burden on their
      practice, and on the need for improving care. FINDINGS: There were 232
      respondents (23%). National Institute for Health and Clinical Excellence (NICE)
      guidance (65%) and professional experience (64%) were the biggest influences on
      OA management. When assessing patients, pain and mobility were most frequently
      assessed, with quality of life, independent living, sleep and depression
      addressed by over half of them. In all, 52% did not use educational materials;
      only a third of users rated their current educational material as good or very
      good. Treatments employed were largely in line with NICE recommendations.
      Prescription review was reported by a high proportion (74%). Achieving adequate
      pain control and lack of time were the most frequently cited challenges, whereas
      more time with patients, collaboration with specialist colleagues and improved
      communication tools were the most common needs identified to improve OA
      management. In summary, national guidelines are an important influence for GP
      treatment of OA. This survey has highlighted issues about the adequacy of
      information available for OA, about GPs' need for more time with OA patients and
      their interaction with specialist colleagues.

PMID- 22464220
TI  - Quality or quantity? Exploring the relationship between Public Open Space
      attributes and mental health in Perth, Western Australia.
AB  - Mental health is a public health priority globally. Public Open Space (POS) may
      enhance mental health by facilitating contact with nature and the development of
      supportive relationships. Despite growing interest in the influence of the built
      environment on mental health, associations between POS attributes and mental
      health remain relatively unexplored. In particular, few studies have examined the
      relative effects of the quantity and quality of POS within a neighbourhood on
      mental health. Guided by a social-ecological framework, this study investigated
      the relationship between POS attributes (i.e., quantity and quality) and better
      mental health (i.e., low risk of psychological distress) in residents of new
      housing developments in the Perth metropolitan area, Western Australia. The
      extent to which relationships between POS attributes and mental health were
      confounded by psychosocial factors (e.g., social support, sense of community) and
      frequent use of POS was also explored. Data were obtained from a cross-sectional
      survey (n = 911), a POS audit, and Geographical Information Systems, and was
      analysed using logistic regression. Approximately 80% of survey participants were
      at low risk of psychological distress. Residents of neighbourhoods with high
      quality POS had higher odds of low psychosocial distress than residents of
      neighbourhoods with low quality POS. This appeared to be irrespective of whether
      or not they used POS. However, the quantity of neighbourhood POS was not
      associated with low psychological distress. From a mental health perspective, POS
      quality within a neighbourhood appears to be more important than POS quantity.
      This finding has policy implications and warrants further investigation.

PMID- 22464221
TI  - Socioeconomic position and physical activity among women in Melbourne, Australia:
      does the use of different socioeconomic indicators matter?
AB  - This study aimed to identify which indicators of socioeconomic position (SEP) are
      independently associated with leisure-time physical activity among women. In
      2005, women (n = 1166; 18-65 years) from Melbourne, Australia, reported their own
      (education, occupation, income), their partner's (education, occupation), their
      household (home ownership, ability to cope with income), and their neighbourhood
      (area-level) SEP, and leisure-time physical activity. Multinomial logistic
      regression examined associations between SEP indicators and leisure-time physical
      activity categorized as: none (no min/week; reference group), insufficient (1-149
      min/week), and sufficient (>=150 min/week). In the fully adjusted model, lower
      education, lower partner's education (where applicable), and non-home ownership
      were independently associated with between 33% and 50% lower odds of sufficient
      physical activity, while lower income and lower area-level SEP were associated
      with 40% lower odds of insufficient physical activity. Understandings of
      socioeconomic inequalities in physical activity among women may be enhanced if a
      range of SEP indicators are used, particularly education, partner's education and
      home ownership.

PMID- 22464222
TI  - Revisiting the immigrant paradox in reproductive health: the roles of duration of
      residence and ethnicity.
AB  - The immigrant paradox refers to the contrasting observations that immigrants
      usually experience similar or better health outcomes than the native-born
      population despite socioeconomic disadvantage and barriers to health care use.
      This paradox, however, has not been examined simultaneously in relation to
      varying degrees of exposure to the receiving society and across multiple outcomes
      and risk factors. To advance knowledge on these issues, we analysed data of the
      Maternity Experiences Survey, a nationally representative cross-sectional survey
      of 6421 Canadian women who delivered singleton infants in 2006-07. We compared
      the prevalence of adverse pregnancy outcomes and related risk factors according
      to women's ethnicity and time since migration to Canada. We calculated
      prevalences and prevalence ratios (PR) with 95% confidence intervals. Compared to
      Canadian-born women of European descent, recent immigrants were at lower risk of
      preterm delivery and morbidity during pregnancy despite having the highest
      prevalence of low income and low support during pregnancy among all groups, but
      the paradox was not observed among immigrants with a longer stay in Canada. In
      contrast, recent immigrants were at higher risk of postpartum depression.
      Immigrants of non-European origin also had higher prevalence of postpartum
      depression, irrespective of their length of residence in Canada, but immigrants
      from European-origin countries did not. Exposure to Canada was also positively
      associated with higher alcohol and tobacco consumption and body mass index.
      Canadian-born women of non-European descent were at higher risk of preterm birth
      and hospitalisation during pregnancy than their European-origin counterparts. Our
      findings suggest that the healthy migrant hypothesis and the immigrant paradox
      have limited generalisability. These hypotheses may be better conceptualised as
      outcome-specific and dependent on immigrants' ethnicity and length of stay in the
      receiving country.

PMID- 22464223
TI  - Trauma and suicide behaviour histories among a Canadian indigenous population: an
      empirical exploration of the potential role of Canada's residential school
      system.
AB  - It has been theorized that suicide behaviours amongst indigenous peoples may be
      an outcome of mass trauma experienced as a result of colonization. In Canada,
      qualitative evidence has suggested that the Indian Residential School System set
      in motion a cycle of trauma, with some survivors reporting subsequent abuse,
      suicide, and other related behaviours. It has been further postulated that the
      effects of trauma can also be passed inter-generationally. Today, there are four
      generations of Canadian First Nations residential school survivors who may have
      transmitted the trauma they experienced to their own children and grandchildren.
      No empirical study has ever been undertaken to demonstrate this dynamic. This
      study is therefore the first to investigate whether a direct or indirect exposure
      to Canada's residential school system is associated with trauma and suicide
      behaviour histories. Data were collected in 2002/2003 from a representative
      sample of Manitoba, Canada, First Nations adults (N = 2953), including
      residential (N = 611) and non-residential school attendees (N = 2342). Regression
      analyses showed that for residential school attendees negative experiences in
      residential school were associated with a history of abuse, and that this history
      and being of younger age was associated with a history of suicide thoughts,
      whereas abuse history only was associated with a history of suicide attempts. For
      First Nations adults who did not attend a residential school, we found that age
      28-44, female sex, not having a partner, and having a parent or grandparent who
      attended a residential school was associated with a history of abuse. This
      history, along with age and having had a parent or grandparent who attended
      residential school was associated with a history of suicide thoughts and
      attempts. In conclusion, this is the first study to empirically demonstrate, at
      the population level, the mental health impact of the residential school system
      on survivors and their children.

PMID- 22464224
TI  - An exo-beta-(1->3)-D-galactanase from Streptomyces sp. provides insights into
      type II arabinogalactan structure.
AB  - An exo-beta-(1->3)-D-galactanase (SGalase1) that specifically cleaves the beta-(1
      >3)-D-galactan backbone of arabinogalactan-proteins (AGPs) was isolated from
      culture filtrates of a soil Streptomyces sp. Internal peptide sequence
      information was used to clone and recombinantly express the gene in E. coli. The
      molecular mass of the isolated enzyme was ~45 kDa, similar to the 48.2 kDa mass
      predicted from the amino acid sequence. The pI, pH and temperature optima for the
      enzyme were ~7.45, 3.8 and 48  degrees C, respectively. The native and
      recombinant enzymes specifically hydrolysed beta-(1->3)-D-galacto-oligo- or poly
      saccharides from the upstream (non-reducing) end, typical of an exo-acting
      enzyme. A second homologous Streptomyces gene (SGalase2) was also cloned and
      expressed. SGalase2 was similar in size (47.9 kDa) and enzyme activity to
      SGalase1 but differed in its pH optimum (pH 5). Both SGalase1 and SGalase2 are
      predicted to belong to the CAZy glycosyl hydrolase family GH 43 based on
      activity, sequence homology and phylogenetic analysis. The K(m) and V(max) of the
      native exo-beta-(1->3)-D-galactanase for de-arabinosylated gum arabic (dGA) were
      19 mg/ml and 9.7 MUmol D-Gal/min/mg protein, respectively. The activity of these
      enzymes is well suited for the study of type II galactan structures and provides
      an important tool for the investigation of the biological role of AGPs in plants.
      De-arabinosylated gum arabic (dGA) was used as a model to investigate the use of
      these enzymes in defining type II galactan structure. Exhaustive hydrolysis of
      dGA resulted in a limited number of oligosaccharide products with a trisaccharide
      of Gal(2)GlcA(1) predominating.

PMID- 22464225
TI  - Analysis of the hydrolysis of inulin using real time 1H NMR spectroscopy.
AB  - The hydrolysis of various carbohydrates was investigated under acidic conditions
      in real time by (1)H NMR spectroscopy, with a focus on the polysaccharide inulin.
      Sucrose was used as a model compound to illustrate the applicability of this
      technique. The hydrolysis of sucrose was shown to follow pseudo first order
      kinetics and have an activation energy of 107.0 kJ mol(-1) (SD 1.7 kJ mol(-1)).
      Inulin, pullulan and glycogen also all followed pseudo first order kinetics, but
      had an initiation phase at least partially generated by the protonation of the
      glycosidic bonds. It was also demonstrated that polysaccharide chain length has
      an effect on the hydrolysis of inulin. For short chain inulin (DPn 18, SD 0.70)
      the activation energy calculated for the hydrolytic cleavage of glucose was
      similar to sucrose at 108.5 kJ mol(-1) (SD 0.60). For long chain inulin (DPn 30,
      SD 1.3) the activation energy for the hydrolytic cleavage of glucose was reduced
      to 80.5 kJ mol(-1) (SD 2.3 kJ mol(-1)). This anomaly has been attributed to
      varied conformations for the two different lengths of inulin chain in solution.

PMID- 22464226
TI  - Triage nurse prediction of hospital admission.
AB  - INTRODUCTION: Numerous factors affect patient flow in the emergency department.
      One important factor that has a negative impact on flow is ED patients waiting
      for an inpatient bed. It currently takes approximately 5 hours from triage to a
      request for an inpatient bed in our emergency department. Knowledge of patients
      requiring admission early in their ED evaluation could speed up the process of
      securing a bed. The objective of this study was to determine if an ED triage
      nurse (TRN) can determine at triage if a patient will be admitted to an inpatient
      unit. A secondary objective was to measure the confidence of the TRN prediction.
      METHODS: A prospective, non-consecutive study was conducted during an 18-day
      period in 2010 in a community hospital emergency department treating 76,000
      patients. Experienced TRNs were trained in the evaluation tool. Immediately after
      the initial TRN evaluation, a determination was made in writing by the TRN
      regarding the likelihood of hospital admission and level of confidence in this
      decision. Patients who did not enter the emergency department through triage
      (ambulance) or were younger than 18 years were excluded. RESULTS: A total of 3514
      patients approached triage. Of these patients, 1866 were eligible for the study
      and 1164 (62%) were enrolled. We excluded 25 subjects because of missing data,
      resulting in 1139 subjects. Missed subjects had the same baseline
      characteristics. A total of 287 (25.2%) hospital admissions occurred. TRN
      predicted 217 admissions, with a sensitivity of 75.6% (95% confidence interval
      [CI] 71.3-79.5) and a specificity of 84.5% (95% CI 83.1-85.8). The TRN reported
      being extremely confident in the prediction 50.1% of the time. In these cases,
      the TRN demonstrated an admission sensitivity of 81.6% (95% CI 76.5-85.8) and
      specificity of 93.1% (95% CI 91.8-94.3). CONCLUSIONS: The TRN demonstrated a high
      sensitivity and specificity in admission prediction at triage and could
      potentially save many hours in requesting an inpatient bed. This increased
      efficiency could result in a more rapid ED throughput and decreased ED boarding.

PMID- 22464227
TI  - Patient and family education in the emergency department: how nurses can help.
AB  - Non-emergent use of the emergency department has grown over the past decade. Lack
      of resources, access to care, medical insurance, and knowledge can all contribute
      to the inappropriate use of the emergency department. In return, the increase in
      the number of patients will then add to the wait time for those who need emergent
      treatment. The role of the emergency nurse can be enhanced by providing discharge
      teaching to patients and families about the proper use of the emergency
      department or where to seek treatment if needed. This education has the potential
      to significantly reduce the number of repeat visits, as well as misuse of the
      emergency department. The purpose of this article is to discuss the importance of
      discharge teaching for the patient and family in the ED setting.

PMID- 22464228
TI  - Biological contribution of UVA wavelengths in non extreme daily UV exposure.

PMID- 22464229
TI  - Molecular interactions of natural and synthetic steroids in female hamsters'
      flank organs.
AB  - BACKGROUND: The initial step of steroidal action on target cells is gene
      activation; therefore, the quantification of mRNA is a direct method for
      comparing the role of different steroids in the skin. OBJECTIVE: This study
      demonstrated the role of several steroids on the mRNA expression encoding for
      different enzymes involved in the lipid metabolism in hamsters' flank organs,
      which are a pilosebaceous complex. METHODS: To determine the effect of treatments
      with testosterone (T) progesterone (P), levonorgestrel (LNG), 17alpha-p
      chlorobenzoyloxy-6-chloropregn-4,6-diene-3,20-dione (5) and 17alpha-p
      chlorobenzoyloxy-4,6-pregnadiene-3,20-dione (6); T and/or LNG; T and 5 or 6; P
      and/or 5 or 6 on the expression of mRNA encoding for lipid enzymes, the steroids
      were applied to the glands; later, the mRNAs expression for the enzymes was
      determined by PCR. The binding of 5 and 6 to the progesterone receptor (PR) was
      also evaluated. RESULTS: Treatments with T, LNG, T+LNG, P, T+P, 5, T+5, T+6, P,
      P+5 and P+6 increased the mRNA expression for glycerol 3-phosphate acyl
      transferase (GPAT), beta-hydroxy-beta-methylglutaryl-CoA synthase (HMG-CoA-S),
      beta-hydroxy-beta-methylglutaryl-CoA reductase (HMG-CoA-R), phosphatidylinositol
      synthase as compared to the controls. However, squalene synthase was increased
      with all treatments except with T+5 and 6; 6 did not significantly increase the
      expression for GPAT or HMG-CoA-S, however it increased the concentration of HMG
      CoA-R enzyme. 5 and 6 bind to the PR, thus indicating that the effect of these
      steroids on the mRNA expression could be the result of their binding. CONCLUSION:
      The lipid metabolism is regulated by several steroids thought different mechanism
      of action, in flank organs.

PMID- 22464230
TI  - Kojic acid-induced IL-6 production in human keratinocytes plays a role in its
      anti-melanogenic activity in skin.
AB  - BACKGROUND: Kojic acid is a fungal metabolite widely used in medicinal and
      cosmetic formulations as a skin-lightening agent based on its de-pigmenting
      activity. Although in human clinical studies kojic acid has been shown to be
      effective in the treatment of hyper-pigmentation disorders such as melasma, the
      reasons for its apparent lack of anti-melanogenic activity in cultured mammalian
      melanocytes are unclear. OBJECTIVES: This study was aimed to elucidate
      pharmacological mechanisms of the in vivo anti-melanogenic activity of kojic acid
      in human skin. METHODS: A primary human melanocyte and keratinocyte co-culture
      system was used to evaluate whether kojic-acid-induced changes in keratinocytes
      were associated with anti-melanogenic activities in melanocytes. The cytokine
      secretion profiles in response to kojic acid were analyzed. RESULTS: Kojic acid
      increased interleukin (IL)-6 and IL-8 production in melanocyte/keratinocyte co
      cultures; however, IL-6 directly inhibited melanogenesis whereas IL-8 did not. In
      melanocyte monocultures, kojic acid did not increase IL-6 production whereas in
      keratinocyte monocultures it significantly up-regulated IL-6 gene and protein
      expression. Therefore, the up-regulation of IL-6 in melanocyte/keratinocyte co
      cultures seems to be originated from kojic acid-induced changes in keratinocytes.
      Anti-IL-6 antibody treatment antagonized the anti-melanogenic effect of kojic
      acid on the co-cultures. CONCLUSIONS: The pharmacological mechanism of kojic acid
      to explain clinically effective anti-melanogenic activity on hyper-pigmented skin
      is associated with the kojic acid-induced IL-6 production in keratinocytes. The
      cross-talk between melanocytes and keratinocytes should be determined in future
      studies on the pharmacological mechanisms of clinically effective dermatological
      drugs acting on the epidermis.

PMID- 22464231
TI  - Resilience and related factors during female Ecuadorian mid-life.
AB  - BACKGROUND: Studies reporting on resilience (capacity to overcome life adversity)
      and the menopausal transition are scarce. OBJECTIVE: To assess resilience and
      related factors in mid-aged Ecuadorian women. METHOD: This was a cross sectional
      study in which 904 women aged 40-59 completed the 14-item Wagnild and Young
      Resilience Scale (WYRS) and a general socio-demographic questionnaire containing
      personal and partner data. Lower total WYRS scores indicate less resilience.
      Internal consistency of the tool was also assessed. RESULTS: Median age of all
      surveyed women was 49 years. A 51.1% were postmenopausal, 43.8% lived high
      altitude, 43.5% were abdominally obese, 12.6% used hormone therapy and 80.8% had
      a partner. Internal consistency was high for the WYRS tool (Cronbach's alpha:
      0.94). Multiple linear regression analysis determined that lower total WYRS
      scores (less resilience) correlated with high altitude residency, more severe hot
      flushes, sedentarism, higher abdominal circumferences and having a partner with
      erectile dysfunction. Contrary to this, higher WYRS scores correlated with higher
      parity and sexual activity. CONCLUSION: As assessed with the WYRS tool, lower
      resilience of this mid-aged Ecuadorian female sample was related to various
      female and partner lifestyle and health issues, not necessarily related per se to
      the ageing process. More research using the tool is warranted.

PMID- 22464232
TI  - Results of needle aponeurotomy for Dupuytren contracture in over 1,000 fingers.
AB  - PURPOSE: To critically review the efficacy, recurrence rate, and complications of
      needle aponeurotomy (NA) for the treatment of Dupuytren contracture. METHODS:
      This was a retrospective study of the results of NA for the treatment of
      Dupuytren contracture. We included in the study all patients who had NA performed
      for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contracture
      of 20 degrees  or greater between March 2005 and May 2008. There were 474
      patients with 1,013 fingers treated. The average age was 62 years (range, 33-92
      y). Pre-procedure MP joint contracture averaged 35 degrees  (range, 15 degrees 
      to 95 degrees ), and PIP joint 50 degrees  (range, 15 degrees  to 110 degrees ).
      Immediately postprocedure and at least 3 years after treatment (range, 3.0-6.2
      y), we measured MP and PIP joint contractures and reviewed records for
      complications. RESULTS: MP joint contractures were corrected an average of 99%
      and PIP contractures an average of 89% immediately postprocedure. At final follow
      up, 72% of the correction was maintained for MP joints and 31% for PIP joints.
      The difference between the final corrections for MP versus PIP joints was
      statistically significant. When we compared the final results of patients age 55
      years and older versus under 55 years, we found a statistically significant
      difference at both MP and PIP joints, with greater correction maintained in the
      older group. Gender differences were not statistically significant. Needle
      aponeurotomy provided successful correction to 5 degrees  or less contracture
      immediately postprocedure in 98% (791) of MP joints and 67% (350) of PIP joints.
      There was recurrence of 20 degrees  or less over the original postprocedure
      corrected level in 80% (646) of MP joints and 35% (183) of PIP joints.
      Complications were rare except for skin tears, which occurred in 3.4% (34) of
      digits. CONCLUSIONS: This study shows that NA is a safe procedure that can be
      performed in an outpatient setting. The complication rate was low, but
      recurrences were frequent in younger patients and for PIP contractures. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22464233
TI  - Functional outcome of glenohumeral fusion in brachial plexus palsy: a report of
      54 cases.
AB  - PURPOSE: The restoration of shoulder function is a major issue in brachial plexus
      palsy. Although several tendon and nerve transfers have been described, shoulder
      arthrodesis remains a reliable technique in this context. This study planned to
      compare surgical and functional outcomes of 2 glenohumeral arthrodesis bone graft
      techniques: massive subacromial corticocancellous versus cancellous only grafts.
      METHODS: We reviewed 54 patients who had shoulder arthrodesis according to 2
      parameters after a mean follow-up of 37 months. The primary outcome measure was
      the rate of fusion according to the surgical technique. A total of 26 patients
      received a massive subacromial corticocancellous bone autograft, and 28 patients
      received only cancellous bone. The secondary outcome measure was the range of
      scapulothoracic motion measured by a video-assisted method according to type of
      neurological lesion. Brachial plexus palsy was complete in 32 cases and partial
      in 22 cases. All patients had recovered active elbow flexion before undergoing
      shoulder arthrodesis. Of the 54 patients, 48 had no postoperative immobilization.
      RESULTS: The overall fusion rate was 76% after the first surgical procedure and
      94% at last follow-up. Reoperation led to fusion in 10 cases, whereas 3 cases
      never fused. Pseudarthrosis rate after first surgery was 4% in the group with
      massive subacromial graft versus 43% in the group with cancellous bone graft. The
      mean range of motion was 59 degrees  in abduction (57 degrees  for complete palsy
      and 62 degrees  for partial palsy) with 42 cases 45 degrees  or greater. The mean
      range of motion was 48 degrees  in rotation (50 degrees  for complete palsy and
      46 degrees  for partial palsy) with 35 cases 45 degrees  or greater. CONCLUSIONS:
      Shoulder fusion provided active abduction greater than 45 degrees  in more than
      75% of cases and active rotation greater than 45 degrees  in almost 65% of cases.
      Using a massive subacromial graft significantly reduced pseudarthrosis rate (P <
      .001). TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 22464234
TI  - Innervation patterns of thumb trapeziometacarpal joint ligaments.
AB  - PURPOSE: The human thumb trapeziometacarpal (TM) joint is a unique articulation
      that allows stability during pinch and grip and great degrees of mobility.
      Because the saddle-shaped articulating surfaces of the TM joint are inherently
      unstable, joint congruity depends on the action of restraining ligaments and
      periarticular muscles. From other joints, it is known that proprioceptive and
      neuromuscular joint stability depend on afferent information from nerve endings
      within ligaments. We hypothesize that the TM joint ligaments may similarly be
      innervated, indicating a possible proprioceptive function of the joint. METHODS:
      We harvested 5 TM joint ligaments in entirety from 10 fresh-frozen cadaver hands
      with no or only minor signs of osteoarthritis and suture-marked them for proximal
      distal orientation. The ligaments harvested were the dorsal radial, dorsal
      central, posterior oblique, ulnar collateral, and anterior oblique ligaments.
      After paraffin-sectioning, we stained the ligaments using a triple-antibody
      immunofluorescent technique and analyzed them using immunofluorescence
      microscopy. RESULTS: Using the triple-stain technique, mechanoreceptors could be
      classified as Pacinian corpuscles, Ruffini endings, or Golgi-like endings. The 3
      dorsal ligaments had significantly more nerve endings than the 2 volar ligaments.
      Most of the nerve endings were close to the bony attachments and significantly
      closer (P = .010) to the metacarpal insertion of each ligament. The anterior
      oblique ligament had little to no innervation in any of the specimens analyzed.
      DISCUSSION: The TM joint ligaments had an abundance of nerve endings in the
      dorsal ligaments but little to no innervation in the anterior oblique ligament.
      The Ruffini ending was the predominant mechanoreceptor type, with a greater
      density in the mobile metacarpal portion of each ligament. CLINICAL RELEVANCE:
      Presence of mechanoreceptors in the dorsal TM joint ligaments infers a
      proprioceptive function of these ligaments in addition to their biomechanical
      importance in TM joint stability.

PMID- 22464235
TI  - Immunology of vascularized composite allotransplantation: a primer for hand
      surgeons.
AB  - Vascularized composite allotransplantation is a recent innovation in the fields
      of transplantation surgery, plastic and reconstructive surgery, and orthopedic
      surgery. The success of hand and face transplantation has been based on extensive
      experience in solid organ transplantation. Advances in understanding the
      immunology of transplantation have had a major role in achieving excellent
      results in this new field. The purpose of this article is to introduce the basics
      of human immunology (innate and adaptive systems) and the immunological basis of
      human transplantation (the importance of human leukocyte antigen, direct and
      indirect pathways of antigen recognition, the 3 signals for T-cell activation,
      and mechanisms and types of allograft rejection) and focus on the mode of action
      of immunosuppressive drugs that have evolved as the mechanisms and pathways for
      rejection have been defined through research. This includes recent studies
      involving the use of costimulatory blockade, regulatory T cells, and tolerance
      induction that have resulted from research in understanding the mechanisms of
      immune recognition and function.

PMID- 22464236
TI  - Clinical research and patient-rated outcome measures in hand surgery.
AB  - High-quality clinical research incorporating standardized outcome assessments is
      necessary to advance the field of hand surgery. Although such research can be
      conducted with little direct cost, effectively answering clinical questions
      requires thoughtful study design. Relevant concepts to consider include sample
      size determination, study end points, data management, and choice of outcome
      measures. Provided the emphasis on, and proliferation of, patient-rated outcome
      measures, the clinician-researcher should consider the unique aspects of commonly
      referenced outcome measures when initiating an investigation.

PMID- 22464237
TI  - Probability and pathophysiology.

PMID- 22464239
TI  - Extravasation injuries: a practice pearl.

PMID- 22464241
TI  - Upper extremity surgery after lymph node dissection--contraindicated or not?

PMID- 22464243
TI  - Re: "current trends in nonoperative and operative treatment of trapeziometacarpal
      osteoarthritis: a survey of US hand surgeons".

PMID- 22464245
TI  - 3.0 T multiparametric prostate MRI using pelvic phased-array coil: utility for
      tumor detection prior to biopsy.
AB  - OBJECTIVE: To evaluate the role of multiparametric magnetic resonance imaging
      (MRI) performed in men without a biopsy-proven diagnosis of prostate cancer using
      follow-up biopsy as the reference standard. MATERIALS AND METHODS: Forty-two
      patients without biopsy-proven cancer and who underwent MRI were included. In all
      patients, MRI was performed at 3T using a pelvic phased-array coil and included
      T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced
      imaging. Thirteen had undergone no previous biopsy, and 29 had undergone at least
      1 previous negative biopsy. All patients underwent prostate biopsy following MRI.
      Two fellowship-trained radiologists in consensus reviewed all cases and
      categorized each lobe as positive or negative for tumor. These interpretations
      were correlated with findings on post-MRI biopsy. RESULTS: Follow-up biopsy was
      positive in 23 lobes in 15 patients (36% of study cohort). On a per-patient
      basis, MRI had a sensitivity of 100%, specificity of 74%, positive predictive
      value (PPV) of 68%, and negative predictive value (NPV) of 100%. On a per-lobe
      basis, MRI had a sensitivity of 65%, specificity of 84%, PPV of 60%, and NPV of
      86%. There was a nearly significant association between Gleason score and tumor
      detection on MRI (P = 0.072). CONCLUSIONS: In our sample, MRI had 100%
      sensitivity in predicting the presence of tumor on subsequent biopsy on a per
      patient basis, suggesting a possible role for MRI in selecting patients with an
      elevated prostatic specific antigen (PSA) to undergo prostate biopsy. However,
      MRI had weaker specificity for prediction of a subsequent positive biopsy, as
      well as weaker sensitivity for tumor on a per-lobe basis, indicating that in
      patients with a positive MRI result, tissue sampling remains necessary for
      confirmation of the diagnosis as well as for treatment planning.

PMID- 22464246
TI  - Influence of polymerization mode and C-factor on cohesive strength of dual-cured
      resin cements.
AB  - OBJECTIVES: The aim of this study is to determine the influence of the C-factor
      and the mode of polymerization on the cohesive strength of various dual-cure
      resin cements. METHODS: Three curing conditions were tested; chemical curing with
      free shrinkage conditions (C=0), and constraint shrinkage conditions (C=25), and
      dual-curing with free shrinkage conditions (C=0). Opaque polyethylene, brass
      (pretreated with Clearfil SE bond), and transparent polyethylene tubes
      respectively, were filled with the different cements. The tubes were 20mm long
      with an inner diameter of 1.6 or 1.8mm. Five cements, DC Core Automix, Panavia F
      2.0, Maxcem, Multilink, and RelyX Unicem, were tested with ten specimens per
      group. The specimens were trimmed to an hour-glass shape with a neck diameter of
      1mm, stored in water (37 degrees C, 24h), and subjected to microtensile testing
      (1mmmin(-1)). SEM analysis was carried out on chemically cured samples of DC Core
      Automix C=0 and C=25. Data were statistically analyzed (Two-way ANOVA, Tukey's
      post hoc test, p<0.05). RESULTS: Most cements showed no significant differences
      between the curing modes. A high C-factor negatively influences the cohesive
      strength of some cements. SEM analysis shows that chemical curing of DC Core
      Automix in a high C-factor environment leads to more and larger microvoids in the
      cement. SIGNIFICANCE: Constraint shrinkage conditions, i.e. a high C-factor, can
      negatively influence the physical properties of a dual-cured resin cement, which
      would clinically be the case in the confined space of a root canal or post space
      preparation.

PMID- 22464247
TI  - Expanding nature's chemical repertoire through metabolic engineering and
      biocatalysis.

PMID- 22464248
TI  - The impact of a prior history of cardiovascular events on outcomes in patients on
      renal replacement therapy.

PMID- 22464249
TI  - Anti-epithelial cell adhesion molecule monoclonal antibody conjugated fluorescent
      nanoparticle biosensor for sensitive detection of colon cancer cells.
AB  - In this paper, a sensitive and selective sensor for detecting colon cancer cells
      based on nanoparticle covalent modified anti-human epithelial cell adhesion
      molecule (EpCAM) antibody is developed. The transmission electron microscope
      (TEM) images showed that the nanoparticle and functionalized nanoparticle had
      good decentrality for application. The NaIO(4) oxidation method, which was used
      as oxidizing antibody for immobilization of conjugating antibody on the silica
      coated fluorescent nanoparticles, maintained the activities of antibodies very
      well. The fluorescence microscopy imaging and flow cytometer (FCM) experiments
      demonstrated that the nanosensor could increase the signal intensity obviously
      and distinguish three kinds of target cells (colo205, sw480 and NCM460) well. The
      membrane and nuclear staining showed the distribution and abundance of EpCAM in
      cells' membrane. It also provides a possibility to quantify special membrane
      proteins on different regions of cells' surface. At the end, the result of
      detecting a simple sample proved that colo205 cells were selected by anti-EpCAM
      antibody nanosensors in this environment, and made a good foundation for
      subsequent research.

PMID- 22464250
TI  - Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis.
AB  - Acrodysostosis is a rare autosomal-dominant condition characterized by facial
      dysostosis, severe brachydactyly with cone-shaped epiphyses, and short stature.
      Moderate intellectual disability and resistance to multiple hormones might also
      be present. Recently, a recurrent mutation (c.1102C>T [p.Arg368*]) in PRKAR1A has
      been identified in three individuals with acrodysostosis and resistance to
      multiple hormones. After studying ten unrelated acrodysostosis cases, we report
      here de novo PRKAR1A mutations in five out of the ten individuals (we found
      c.1102C>T [p.Arg368(*)] in four of the ten and c.1117T>C [p.Tyr373His] in one of
      the ten). We performed exome sequencing in two of the five remaining individuals
      and selected phosphodiesterase 4D (PDE4D) as a candidate gene. PDE4D encodes a
      class IV cyclic AMP (cAMP)-specific phosphodiesterase that regulates cAMP
      concentration. Exome analysis detected heterozygous PDE4D mutations (c.673C>A
      [p.Pro225Thr] and c.677T>C [p.Phe226Ser]) in these two individuals. Screening of
      PDE4D identified heterozygous mutations (c.568T>G [p.Ser190Ala] and c.1759A>C
      [p.Thr587Pro]) in two additional acrodysostosis cases. These mutations occurred
      de novo in all four cases. The four individuals with PDE4D mutations shared
      common clinical features, namely characteristic midface and nasal hypoplasia and
      moderate intellectual disability. Metabolic screening was normal in three of
      these four individuals. However, resistance to parathyroid hormone and
      thyrotropin was consistently observed in the five cases with PRKAR1A mutations.
      Finally, our study further supports the key role of the cAMP signaling pathway in
      skeletogenesis.

PMID- 22464251
TI  - Rare mutations in XRCC2 increase the risk of breast cancer.
AB  - An exome-sequencing study of families with multiple breast-cancer-affected
      individuals identified two families with XRCC2 mutations, one with a protein
      truncating mutation and one with a probably deleterious missense mutation. We
      performed a population-based case-control mutation-screening study that
      identified six probably pathogenic coding variants in 1,308 cases with early
      onset breast cancer and no variants in 1,120 controls (the severity grading was p
      < 0.02). We also performed additional mutation screening in 689 multiple-case
      families. We identified ten breast-cancer-affected families with protein
      truncating or probably deleterious rare missense variants in XRCC2. Our
      identification of XRCC2 as a breast cancer susceptibility gene thus increases the
      proportion of breast cancers that are associated with homologous recombination
      DNA-repair dysfunction and Fanconi anemia and could therefore benefit from
      specific targeted treatments such as PARP (poly ADP ribose polymerase)
      inhibitors. This study demonstrates the power of massively parallel sequencing
      for discovering susceptibility genes for common, complex diseases.

PMID- 22464252
TI  - Exome sequencing identifies PDE4D mutations in acrodysostosis.
AB  - Acrodysostosis is a dominantly-inherited, multisystem disorder characterized by
      skeletal, endocrine, and neurological abnormalities. To identify the molecular
      basis of acrodysostosis, we performed exome sequencing on five genetically
      independent cases. Three different missense mutations in PDE4D, which encodes
      cyclic AMP (cAMP)-specific phosphodiesterase 4D, were found to be heterozygous in
      three of the cases. Two of the mutations were demonstrated to have occurred de
      novo, providing strong genetic evidence of causation. Two additional cases were
      heterozygous for de novo missense mutations in PRKAR1A, which encodes the cAMP
      dependent regulatory subunit of protein kinase A and which has been recently
      reported to be the cause of a form of acrodysostosis resistant to multiple
      hormones. These findings demonstrate that acrodysostosis is genetically
      heterogeneous and underscore the exquisite sensitivity of many tissues to
      alterations in cAMP homeostasis.

PMID- 22464254
TI  - Primate genome gain and loss: a bone dysplasia, muscular dystrophy, and bone
      cancer syndrome resulting from mutated retroviral-derived MTAP transcripts.
AB  - Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is an
      autosomal-dominant syndrome characterized by bone dysplasia, myopathy, and bone
      cancer. We previously mapped the DMS-MFH tumor-suppressing-gene locus to
      chromosomal region 9p21-22 but failed to identify mutations in known genes in
      this region. We now demonstrate that DMS-MFH results from mutations in the most
      proximal of three previously uncharacterized terminal exons of the gene encoding
      methylthioadenosine phosphorylase, MTAP. Intriguingly, two of these MTAP exons
      arose from early and independent retroviral-integration events in primate genomes
      at least 40 million years ago, and since then, their genomic integration has
      gained a functional role. MTAP is a ubiquitously expressed homotrimeric-subunit
      enzyme critical to polyamine metabolism and adenine and methionine salvage
      pathways and was believed to be encoded as a single transcript from the eight
      previously described exons. Six distinct retroviral-sequence-containing MTAP
      isoforms, each of which can physically interact with archetype MTAP, have been
      identified. The disease-causing mutations occur within one of these retroviral
      derived exons and result in exon skipping and dysregulated alternative splicing
      of all MTAP isoforms. Our results identify a gene involved in the development of
      bone sarcoma, provide evidence of the primate-specific evolution of certain parts
      of an existing gene, and demonstrate that mutations in parts of this gene can
      result in human disease despite its relatively recent origin.

PMID- 22464255
TI  - Heart transplantation research in the next decade--a goal to achieving evidence
      based outcomes: National Heart, Lung, And Blood Institute Working Group.
AB  - The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group
      (WG) on August 5 to 6, 2010 in Bethesda, Maryland to discuss future directions of
      research in heart transplantation (HT). The WG was composed of researchers with
      expertise in the basic science, clinical science, and epidemiological aspects of
      advanced heart failure and HT. These experts were asked to identify the highest
      priority research gaps in the field and make recommendations for future research
      strategies. The WG was also asked to include approaches that capitalize on
      current scientific opportunities and focus on areas that required unique NHLBI
      leadership. Finally, the WG was charged with developing recommendations that
      would have short- and long-term impact on the field of HT. The WG participants
      reviewed key areas in HT and identified the most urgent knowledge gaps. These
      gaps were then organized into the following 4 specific research directions: 1)
      enhanced phenotypic characterization of the pre-transplant population; 2) donor
      recipient optimization strategies; 3) individualized immunosuppression therapy;
      and, 4) investigations of immune and non-immune factors affecting late cardiac
      allograft outcomes. Finally, because the HT population is relatively small
      compared with other patient groups, the WG strongly urged concerted efforts to
      enroll every transplant recipient into a clinical study and to increase
      collaborative networks to optimize research in this field.

PMID- 22464253
TI  - Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for
      systemic lupus erythematosus in a large-scale multiracial replication study.
AB  - Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder
      characterized by the loss of tolerance to self-antigens and dysregulated
      interferon responses. The etiology of SLE is complex, involving both heritable
      and environmental factors. Candidate-gene studies and genome-wide association
      (GWA) scans have been successful in identifying new loci that contribute to
      disease susceptibility; however, much of the heritable risk has yet to be
      identified. In this study, we sought to replicate 1,580 variants showing
      suggestive association with SLE in a previously published GWA scan of European
      Americans; we tested a multiethnic population consisting of 7,998 SLE cases and
      7,492 controls of European, African American, Asian, Hispanic, Gullah, and
      Amerindian ancestry to find association with the disease. Several genes relevant
      to immunological pathways showed association with SLE. Three loci exceeded the
      genome-wide significance threshold: interferon regulatory factor 8 (IRF8;
      rs11644034; p(meta-Euro) = 2.08 * 10(-10)), transmembrane protein 39A (TMEM39A;
      rs1132200; p(meta-all) = 8.62 * 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48
      * 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona
      pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and
      haplotype analysis of IRF8 indicated that three independent effects tagged by
      rs8046526, rs450443, and rs4843869, respectively, were required for risk in
      individuals of European ancestry. Eleven additional replicated effects (5 * 10(
      8) < p(meta-Euro) < 9.99 * 10(-5)) were observed with CFHR1, CADM2,
      LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and
      STXBP6. The results of this study increase the number of confirmed SLE risk loci
      and identify others warranting further investigation.

PMID- 22464256
TI  - The federal audit of implantable cardioverter-defibrillator implants: lessons
      learned.
AB  - The federal government has investigated a large number of institutions regarding
      concerns that implantable cardioverter-defibrillator procedures were performed in
      violation of the criteria set forth in a National Coverage Determination. We
      describe our experience and responses to such an audit, as well as the to
      complexities and nuances of practicing evidence-based medicine in the setting of
      heavy regulatory oversight.

PMID- 22464257
TI  - Impact of metabolic syndrome on procedural outcomes in patients with atrial
      fibrillation undergoing catheter ablation.
AB  - OBJECTIVES: The aim of this study was to investigate impact of metabolic syndrome
      (MS) on outcomes of catheter ablation in patients with atrial fibrillation (AF)
      in terms of recurrence and quality of life (QoL). BACKGROUND: MS, a
      proinflammatory state with hypertension, diabetes, dyslipidemia, and obesity, is
      presumed to be a close associate of AF. METHODS: In this prospective study, 1,496
      consecutive patients with AF undergoing first ablation (29% with paroxysmal AF,
      26% with persistent AF, and 45% with long-standing persistent AF) were classified
      into those with MS (group 1; n = 485) and those without MS (group 2; n = 1,011).
      Patients were followed for recurrence and QoL. The Medical Outcomes Study SF-36
      Health Survey was used to assess QoL at baseline and 12 month after ablation.
      RESULTS: After 21 +/- 7 months of follow-up, 189 patients in group 1 (39%) and
      319 in group 2 (32%) had arrhythmia recurrence (p = 0.005). When stratified by AF
      type, patients with nonparoxysmal AF in group 1 failed more frequently compared
      with those in group 2 (150 [46%] vs. 257 [35%], p = 0.002); no difference existed
      in the subgroup with paroxysmal AF (39 [25%] vs. 62 [22%], p = 0.295). Group 1
      patients had significantly lower baseline scores on all SF-36 Health Survey
      subscales. At follow-up, both mental component summary (Delta5.7 +/- 2.5, p <
      0.001) and physical component summary (Delta9.1 +/- 3.7, p < 0.001) scores
      improved in group 1, whereas only mental component summary scores (Delta4.6 +/-
      2.8, p = 0.036) were improved in group 2. In the subgroup with nonparoxysmal AF,
      MS, sex, C-reactive protein >=0.9 mg/dl, and white blood cell count were
      independent predictors of recurrence. CONCLUSIONS: Baseline inflammatory markers
      and the presence of MS predicted higher recurrence after single-catheter ablation
      only in patients with nonparoxysmal AF. Additionally, significant improvements in
      QoL were observed in the post-ablation MS population.

PMID- 22464258
TI  - What causes atrial fibrillation and why do we fail with ablation?: insights from
      metabolic syndrome.

PMID- 22464259
TI  - A randomized, 2-period, crossover design study to assess the effects of
      dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state
      pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.
AB  - OBJECTIVES: The aim of this study was to assess the effects of different proton
      pump inhibitors (PPIs) on the steady-state pharmacokinetics and pharmacodynamics
      of clopidogrel. BACKGROUND: Metabolism of clopidogrel requires cytochrome P450s
      (CYPs), including CYP2C19. However, PPIs may inhibit CYP2C19, potentially
      reducing the effectiveness of clopidogrel. METHODS: A randomized, open-label, 2
      period, crossover study of healthy subjects (n = 160, age 18 to 55 years,
      homozygous for CYP2C19 extensive metabolizer genotype, confined, standardized
      diet) was conducted. Clopidogrel 75 mg with or without a PPI (dexlansoprazole 60
      mg, lansoprazole 30 mg, esomeprazole 40 mg, or, as a positive control to maximize
      potential interaction and demonstrate assay sensitivity, omeprazole 80 mg) was
      given daily for 9 days. Pharmacokinetics and pharmacodynamics were assessed on
      days 9 and 10. Pharmacodynamic end-points were vasodilator-stimulated
      phosphoprotein P2Y(12) platelet reactivity index, maximal platelet aggregation to
      5 and 20 MUmol/l adenosine diphosphate, and VerifyNow P2Y12 platelet response
      units. RESULTS: Pharmacokinetic and pharmacodynamic responses with omeprazole
      demonstrated assay sensitivity. The area under the curve for clopidogrel active
      metabolite decreased significantly with esomeprazole but not with dexlansoprazole
      or lansoprazole. Similarly, esomeprazole but not dexlansoprazole or lansoprazole
      significantly reduced the effect of clopidogrel on vasodilator-stimulated
      phosphoprotein platelet reactivity index. All PPIs decreased the peak plasma
      concentration of clopidogrel active metabolite (omeprazole > esomeprazole >
      lansoprazole > dexlansoprazole) and showed a corresponding order of potency for
      effects on maximal platelet aggregation and platelet response units. CONCLUSIONS:
      Generation of clopidogrel active metabolite and inhibition of platelet function
      were reduced less by the coadministration of dexlansoprazole or lansoprazole with
      clopidogrel than by the coadministration of esomeprazole or omeprazole. These
      results suggest that the potential of PPIs to attenuate the efficacy of
      clopidogrel could be minimized by the use of dexlansoprazole or lansoprazole
      rather than esomeprazole or omeprazole.

PMID- 22464260
TI  - Effects of atrial fibrillation on treatment of mitral regurgitation in the
      EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) randomized trial.
AB  - OBJECTIVES: The purpose of this study was to characterize patients with mitral
      regurgitation (MR) and atrial fibrillation (AF) treated percutaneously using the
      MitraClip device (Abbott Vascular, Abbott Park, Illinois) and compare the results
      with surgery in this population. BACKGROUND: The EVEREST II (Endovascular Valve
      Edge-to-Edge Repair Study) randomized controlled trial compared a less invasive
      catheter-based treatment for MR with surgery, providing an opportunity to assess
      the impact of AF on the outcomes of both the MitraClip procedure and surgical
      repair. METHODS: The study population included 264 patients with moderately
      severe or severe MR assessed by an independent echocardiographic core laboratory.
      Comparison of safety and effectiveness study endpoints at 30 days and 1 year were
      made using both intention-to-treat and per-protocol (cohort of patients with MR
      <=2+ at discharge) analyses. RESULTS: Pre-existing AF was present in 27% of
      patients. These patients were older, had more advanced disease, and were more
      likely to have a functional etiology. Similar reduction of MR to <=2+ before
      discharge was achieved in patients with AF (83%) and in patients without AF (75%,
      p = 0.3). Freedom from death, mitral valve surgery for valve dysfunction, and MR
      >2+ was similar at 12 months for AF patients (64%) and for no-AF patients (61%, p
      = 0.3). At 12 months, MR reduction to <2+ was greater with surgery than with
      MitraClip, but there was no interaction between rhythm and MR reduction, and no
      difference in all-cause mortality between patients with and patients without AF.
      CONCLUSIONS: Atrial fibrillation is associated with more advanced valvular
      disease and noncardiac comorbidities. However, acute procedural success, safety,
      and 1-year efficacy with MitraClip therapy is similar for patients with AF and
      without AF.

PMID- 22464261
TI  - Sustained improvement in perfusion and flow reserve after temporally separated
      delivery of vascular endothelial growth factor and angiopoietin-1 plasmid
      deoxyribonucleic acid.
AB  - OBJECTIVES: The aim of this study was to compare temporally separated vascular
      endothelial growth factor (VEGF) and angiopoietin (Ang)-1 delivery with
      concomitant delivery or single VEGF delivery, for therapeutic angiogenesis in
      chronic ischemia. BACKGROUND: Single gene delivery of VEGF results in immature
      neovessels that ultimately regress. Endogenously, VEGF acts early to initiate
      angiogenesis, whereas Ang-1 acts later to induce vessel maturation. Timing VEGF
      and Ang-1 gene delivery to mimic endogenous angiogenesis might be more effective
      for sustained neovascularization. METHODS: Unilateral hindlimb ischemia was
      induced in 170 rats. Ultrasound-mediated gene delivery was performed with
      cationic microbubbles and plasmid deoxyribonucleic acid. Groups included VEGF at
      2 weeks, VEGF/Ang-1 at 2 weeks, VEGF at 2 weeks with Ang-1 at 4 weeks, and
      untreated control subjects. At 2, 4, and 8 weeks after ligation, blood flow and
      flow reserve (FR) were assessed by contrast-enhanced ultrasound. Vascular
      density, organization, and supporting cell coverage were assessed by fluorescent
      microangiography and immunohistochemistry. RESULTS: In untreated control
      subjects, blood flow, FR, and vessel density remained reduced. The VEGF delivery
      improved flow and vessel density at 4 weeks; however, FR remained low, supporting
      cell coverage was poor, and flow and vessel density regressed by 8 weeks. The
      VEGF/Ang-1 co-delivery marginally increased flow and vessel density; however, FR
      and supporting cell coverage improved. After temporally separated VEGF and Ang-1
      delivery, blood flow, vessel density, and FR increased and were sustained, with
      improved pericyte coverage at 8 weeks. CONCLUSIONS: In conclusion, temporally
      separated VEGF and Ang-1 gene therapy results in sustained and functional
      neovascularization.

PMID- 22464262
TI  - Large interatrial thrombus-in-transit resulting in acute myocardial infarction
      complicated by atrioventricular block and cardiogenic shock.

PMID- 22464263
TI  - President's page. The ACC in 2012: transforming cardiovascular care, step by
      step.

PMID- 22464264
TI  - The good, the bad, and the atherogenic.

PMID- 22464266
TI  - Skeletal muscle disease as noncardiac cause of cardiac troponin T elevation.

PMID- 22464268
TI  - Multimodality imaging of giant coronary artery aneurysms in immunoglobulin g4
      related sclerosing disease.

PMID- 22464269
TI  - [Rectal leiomyoma: endoscopic resection].

PMID- 22464270
TI  - Influence of constrained visual and somatic senses on controlling centre of mass
      during sit-to-stand.
AB  - This study aimed to investigate the manner in which healthy individuals execute
      robust whole body movements despite unstable body structure from the perspective
      of perception-action coupling. Twelve healthy adults performed sit-to-stand (STS)
      movements under conditions of constrained visual and somatic senses. During this
      movement, centre of mass (COM) of the body in the anterior-posterior, upward
      downward and right-left directions was computed. The conditions of perceptual
      constraint were set as vision-restricted, somatosensory-restricted, vision- and
      somatosensory-restricted, and normal conditions. To evaluate COM control under
      these perceptual constraints, the variability in position and velocity of COM
      were assessed. The variabilities in COM velocity in the anterior-posterior and
      upward-downward directions decreased around the lift-off period only when both
      vision and somatic senses were constrained, whereas the variability of the COM
      position in the right-left direction increased under the somatosensory-restricted
      condition. Our findings suggested that control of COM velocity was enhanced in
      the major moving directions (anterior and upward directions) around the lift-off
      period during STS when both modalities of perception with regard to postural
      orientation were constrained. These motor regulations with perceptual constraints
      facilitate better adaptation to changes in body and environmental situations in
      daily life.

PMID- 22464271
TI  - Integrated kinematics-kinetics-plantar pressure data analysis: a useful tool for
      characterizing diabetic foot biomechanics.
AB  - The fundamental cause of lower-extremity complications in diabetes is chronic
      hyperglycemia leading to diabetic foot ulcer pathology. While the relationship
      between abnormal plantar pressure distribution and plantar ulcers has been widely
      investigated, little is known about the role of shear stress. Moreover, the
      mutual relationship among plantar pressure, shear stress, and abnormal kinematics
      in the etiology of diabetic foot has not been established. This lack of knowledge
      is determined by the lack of commercially available instruments which allow such
      a complex analysis. This study aims to develop a method for the simultaneous
      assessment of kinematics, kinetics, and plantar pressure on foot subareas of
      diabetic subjects by means of combining three commercial systems. Data were
      collected during gait on 24 patients (12 controls and 12 diabetic neuropathics)
      with a motion capture system synchronized with two force plates and two
      baropodometric systems. A four segment three-dimensional foot kinematics model
      was adopted for the subsegment angles estimation together with a three segment
      model for the plantar sub-area definition during gait. The neuropathic group
      exhibited significantly excessive plantar pressure, ground reaction forces on
      each direction, and a reduced loading surface on the midfoot subsegment (p<0.04).
      Furthermore the same subsegment displayed excessive dorsiflexion, external
      rotation, and eversion (p<0.05). Initial results showed that this methodology may
      enable a more appropriate characterization of patients at risk of foot
      ulcerations, and help planning prevention programs.

PMID- 22464272
TI  - [Impact of precariousness on quality of prenatal detection: Lariboisiere hospital
      experience in Paris].
AB  - CONTEXT: The objective of our study was to estimate the impact of the
      precariousness on the quality of the care in antenatal diagnosis of the patients
      followed to Lariboisiere (Parisian service of gynaecology obstetrics situated in
      a district of the capital discriminated socially) over a period of 3 months.
      PATIENTS: All the patients undergoing a prenatal diagnosis consultation in
      Lariboisiere Hospital between February and April 2008. Patients were split in two
      groups according to their precariousness (economic or psychosocial) or not.
      Criteria studied were: initial purpose of the prenatal consultation, quality of
      the first trimester ultrasound exam, access to the integral calculus in Down
      Syndrome detection, lateness of care between the diagnosis and the prenatal
      consultation. The second part of this analysis was to evaluate if precariousness
      was associated with organizational problem in prenatal diagnosis. RESULTS: Fifty
      nine patients were included: 29 (49%) were identified as being in a
      precariousness situation. The initial purpose of the consultation was the same in
      the two groups. Precariousness was associated to organizational problems for the
      prenatal diagnosis consultation (72 vs. 47%, P=0.004). Thirty-five patients (59%)
      have met organizational problems for the prenatal diagnosis consultation. Were
      associated to organizational problems: precariousness (60% vs. 33%, P=0.04), low
      education level (86 vs. 54%, P=0.007) and single mother (23% vs. 0%, P=0.001).
      CONCLUSION: This work shows the negative impact of precariousness on the prenatal
      diagnosis. Prevention may improve the information and the quality of care given
      to these patients.

PMID- 22464273
TI  - [Practices for management of grave postpartum haemorrhage after vaginal delivery:
      a population-based study in 106 French maternity units].
AB  - OBJECTIVES: Describe management of severe postpartum haemorrhages (PPH) and its
      compliance with national guidelines and identify determinants of non-optimal
      care. PATIENTS AND METHOD: Population-based cohort study of 1379 women with
      severe PPH due to uterine atony after vaginal delivery, conducted in 106 French
      maternity units between December 2004 and November 2006. Severe PPH was defined
      by a peripartum haemoglobin drop of 4g/dL or more, blood loss of 1000 mL or more,
      hysterectomy, or transfer to intensive care for PPH. The frequency of each
      recommended procedure for the management of PPH was described. Associations
      between quality of care and both individual and institutional characteristics
      were assessed by univariate analysis and multivariate logistic regression.
      RESULTS: Management of severe PPH was not optimal in 65.9% of cases. The
      recommended components that were applied least often were administration of
      second line uterotonics, and transfusion of patients with a low haemoglobin.
      After adjustment for individual characteristics, the risk of either non- or
      suboptimal care was significantly higher in non-university public maternity units
      (aOR 2.62 [95% CI: 1.49-4.54]) compared with university hospital units, in units
      with fewer than 2000 annual deliveries (aOR 2.32 [95% CI: 1.49-3.57]), and in
      units without an obstetrician always present (aOR 1.96 [95% CI: 1.26-3.03]).
      CONCLUSIONS: Management practices for severe PPH can be improved, to an extent
      that varies by component of care and type of hospital. A qualitative approach
      should help to identify the individual and organizational factors explaining why
      guidelines are not fully applied.

PMID- 22464274
TI  - [Acute pulmonary edema and pregnancy: a descriptive study of 15 cases and review
      of the literature].
AB  - OBJECTIVE: To describe the incidence and the etiologies of acute pulmonary edema
      (APE) and the diagnostic procedure used during pregnancy and immediate post
      partum. MATERIALS AND METHODS: We analyzed records from a search of codes of
      heart failure and APE as well as from the term "pulmonary edema" in computerized
      obstetric records from 2002 to 2010 in a university center of level 3. We
      identified maternal characteristics, the term of appearance and route of
      delivery, the time between symptoms and diagnosis, additional tests performed,
      and data from echocardiography. RESULTS: Fifteen patients had an APE during
      pregnancy or in the immediate post-partum period during the study period (0.05%).
      The mean age was 28.6 years and the mean term of appearance was 31.2+/-3.1 weeks
      of amenorrhea. The diagnosis was made in 11 cases (73.3%) before delivery and in
      four during post-partum. The main etiology was preeclampsia (46.6%) followed by
      heart disease (26.7%), then tocolysis and overfilling (13.3%). In 55% of cases,
      we found a diagnostic wander characterized by carrying out further unnecessary
      tests. The echocardiography has led to a change in management in 27.3% of cases.
      CONCLUSION: The APE is a rare event during pregnancy and the post-partum period
      and its main etiology is preeclampsia. Some other etiologies are avoidable like
      the use of beta-agonists by intravenous route. The diagnosis is sometimes
      difficult, but the realization of a chest X-ray, a simple and inexpensive test,
      is enough to confirm it.

PMID- 22464275
TI  - Spatial distribution of bottlenose dolphins (Tursiops truncatus) inferred from
      stable isotopes and priority organic pollutants.
AB  - Differences in priority organic pollutants (POPs), analyzed by gas chromatography
      mass spectrometry, and stable isotope ratios (delta(13)C, delta(34)S, and
      delta(15)N; analyzed by isotope ratio-mass spectrometry), divide 77 bottlenose
      dolphins (Tursiops truncatus) from the Florida Gulf Coast into three distinct
      groups. POP levels reflect human population and historical contamination along
      the coast. In the least disturbed site, concentrations of SigmaPOP in male
      dolphins were 18,000 ng g(-1)+/-6000 (95% confidence interval here and
      throughout); in the intermediate bay, males had SigmaPOP concentrations of 19,000
      ng g(-1)+/-10,000. St Andrews Bay was home to dolphins with the highest SigmaPOP
      concentrations: 44,000 ng g(-1)+/-10,300. delta(34)S and delta(15)N, differed
      significantly between St. George Sound dolphins and those frequenting each of the
      other two bays, but not between St. Andrews and St. Joseph Bays. SigmaPOP
      concentrations were statistically higher in dolphins frequenting St. Andrews Bay,
      but were not significantly different between dolphins occupying St. Joseph Bay
      and St. George Sound. Thus, using either POP or isotope values alone, we would
      only be able to identify two dolphin groups, but when POP and isotope data are
      viewed cumulatively, the results clearly define three distinct communities
      occupying this region.

PMID- 22464276
TI  - Accuracy of computed tomographic angiography compared to digital subtraction
      angiography in the diagnosis of intracranial stenosis and its impact on clinical
      decision-making.
AB  - BACKGROUND: Few studies to date have examined the accuracy of computed
      tomographic angiography (CTA) compared to digital subtraction angiography (DSA)
      in diagnosing intracranial stenosis. The purpose of this study was to compare CTA
      to DSA in diagnosing intracranial stenosis and to explore the impact of the
      addition of DSA on the management of stroke patients. METHODS: We retrospectively
      reviewed all ischemic stroke or patients with transient ischemic attack who
      underwent CTA and DSA within 30 days of each other at our institution between
      January 2008 and July 2011. For each study, 2 blinded observers rated the degree
      of stenosis of 11 intracranial vessels. Disagreements were adjudicated by a third
      blinded observer. Sensitivity, specificity, negative predictive value, and
      receiver operating characteristic curves were determined using DSA as the
      criterion standard. All patient charts were reviewed to determine if the addition
      of DSA to CTA impacted clinical management. RESULTS: Six hundred twenty-seven
      arterial segments were reviewed. The sensitivity of CTA to diagnose stenosis >50%
      was 96.6% (95% confidence interval [CI] 88.1-99.6), specificity 99.4% (95% CI
      98.1-99.9), and negative predictive value 99.6% (95% CI 98.4-99.9). The
      intraclass correlation between CTA and DSA measurements was 0.96 (95% CI 0.95
      0.97). Five of 57 patients underwent intracranial stenting procedures during the
      study period. All 5 lesions were correctly characterized as having >70% stenosis
      on CTA. Of the remaining 52 patients, none had clinical management change based
      on DSA findings. CONCLUSIONS: CTA has a high sensitivity and specificity compared
      to DSA to diagnose intracranial stenosis. The addition of DSA to CTA may not
      affect clinical management in most patients with suspected stenosis.

PMID- 22464277
TI  - Thromobolysis for acute ischemic stroke: is intra-arterial better than
      intravenous? A treatment effects model.
AB  - BACKGROUND: Three randomized trials of intra-arterial thrombolysis (IAT) for
      acute ischemic stroke <= 6 hours were conducted without intravenous tissue
      plasminogen activator (IV-tPA) treatment of patients in the control groups now
      known to benefit. METHODS: The effect of IV-tPA treatment on 130 control subjects
      in the Prolyse in Acute Cerebral Thromboembolism (PROACT), PROACT II, and Middle
      Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) studies was
      modeled using linearly weighted time-dependent odds ratios (ORs) from pooled IV
      tPA trials. In the PROACT trials, the model assumed that 50% (36/73) were treated
      at 4.5 hours, the median time to arteriography. For MELT, the model assumed
      treatment at arrival plus 90 minutes based on hospital arrival times obtained
      from the principal investigator. The OR of 1.31 for all 130 controls (91 presumed
      treated <= 4.5 hours; OR 1.44) was applied to the original control data to derive
      the adjusted control outcome, and this was compared to the IAT group. Sensitivity
      analyses were performed. RESULTS: Meta-analysis of the original data revealed a
      statistically significant benefit for IAT (P = .03). After adjustment for the
      effect of IV-tPA in controls, there was no longer a significant treatment benefit
      for IAT (P = .26). Loss of significant IAT treatment benefit persisted if either
      the OR for benefit of IV-tPA or the number of treated controls was more than
      halved. These 3 randomized trials of IAT for acute ischemic stroke <= 6 hours
      would not likely have shown a benefit if eligible controls had been treated with
      IV-tPA. CONCLUSIONS: Whether IAT is superior to IV-tPA in IV-tPA-eligible
      patients or better than placebo in IV-tPA-ineligible patients remains to be
      determined.

PMID- 22464278
TI  - Bone-seeking TRAP conjugates: surprising observations and their implications on
      the development of gallium-68-labeled bisphosphonates.
AB  - BACKGROUND: Bisphosphonates possess strong affinity to bone. 99mTc bisphosphonate
      complexes are widely used for bone scintigraphy. For positron emission tomography
      (PET) bone imaging, Ga-68-based PET tracers based on bisphosphonates are highly
      desirable. FINDINGS: Two trimeric bisphosphonate conjugates of the
      triazacyclononane-phosphinate (TRAP) chelator were synthesized, labeled with Ga
      68, and used for microPET imaging of bone in male Lewis rats. Both Ga-68 tracers
      show bone uptake and, thus, are suitable for PET bone imaging. Surprisingly, Ga
      71 nuclear magnetic resonance data prove that Ga(III) is not located in the
      chelating cavity of TRAP and must therefore be bound by the conjugated
      bisphosphonate units. CONCLUSION: The intrinsic Ga-68 chelating properties of
      TRAP are not needed for Ga-68 PET bone imaging with TRAP-bisphosphonate
      conjugates. Here, TRAP serves only as a trimeric scaffold. For preparation of Ga
      68-based bone seekers for PET, it appears sufficient to equip branched scaffolds
      with multiple bisphosphonate units, which serve both Ga-68-binding and bone
      targeting purposes.

PMID- 22464279
TI  - Effects of short-chain galacto- and long-chain fructo-oligosaccharides on
      systemic and local immune status during pregnancy.
AB  - Nondigestible oligosaccharides can positively influence health via various
      mechanisms. During pregnancy, supplementation of nondigestible oligosaccharides
      has positive effects on hypertension and metabolism and may be used to ameliorate
      pregnancy-related metabolic disturbances. In the nonpregnant state, nondigestible
      oligosaccharides have been shown to induce a tolerogenic immune response mediated
      by T-regulatory cells. Since relatively little is known about the effects of
      nondigestible oligosaccharides on the immune system during pregnancy, pregnant
      mice were supplemented with a specific mixture of short-chain galacto- and long
      chain fructo-oligosaccharides (scGOS/lcFOS; ratio 9:1). Systemic and local immune
      parameters were analyzed on day 18 of pregnancy. This study shows that, compared
      with virgin mice, scGOS/lcFOS supplementation appears to elicit a more
      tolerogenic immune reaction in pregnant mice and supplementation does not
      increase the Th1-dependent delayed type hypersensitivity response in pregnant
      mice as it does in virgin mice.

PMID- 22464280
TI  - The salience of existential concerns across the cancer control continuum.
AB  - Despite significant improvement in cancer survival, the fear of death still
      remains rooted in individuals' beliefs about cancer. Existential fears pertaining
      to cancer cut across the cancer control continuum and taint decisions related to
      prevention, screening, surveillance, and follow-up recommendations, as well as
      the overall management of cancer-related issues. However, individuals are
      innately predisposed to cope with their cancer-related fears through mechanisms
      such as reliance on the process of meaning making. To better appreciate the
      potential impact of existential concerns across the cancer control continuum, the
      Temporal Existential Awareness and Meaning Making (TEAMM) model is proposed. This
      tripartite model depicts three types of perceived threats to life related to
      cancer including a "social awareness" (i.e., cancer signals death), "personalized
      awareness" (i.e., I could die from cancer), and the "lived experience" (i.e., It
      feels like I am dying from cancer). This construal aims to enhance our
      understanding of the personal and contextual resources that can be mobilized to
      manage existential concerns and optimize cancer control efforts. As such,
      existential discussions should be considered in any cancer-related supportive
      approach whether preventive, curative, or palliative, and not be deferred only
      until the advanced stages of cancer or at end of life. Further delineation and
      validation of the model is needed to explicitly recognize and depict how
      different levels of existential awareness might unfold as individuals grapple
      with a potential, actual, or recurrent cancer. 

PMID- 22464281
TI  - [Changes in the complaints made to a General and Gastrointestinal Surgery
      Department after a change in hospital structure and function].
AB  - OBJECTIVE: The complaints to a medical service are a measure of the quality of
      health care perceived by the patients. The aim of this study was to analyse the
      differences found in the percentage of complaints made to the General and
      Gastrointestinal Surgery Department (GGSD) with the changes made due to moving to
      a new hospital. MATERIAL AND METHODS: A longitudinal study of the percentage of
      complaints made to the GGSD in two 6 month periods in the same year (periods A
      and B). The Department was moved to a new hospital between the two periods. The
      percentage complaints associated with the hospital and outpatient activity is
      compared. RESULTS: The percentage complaints made to the GGSD was 3.02% directed
      at the hospital service and 0.44% to outpatient care. When both periods were
      compared, a statistically significant difference was observed in the hospital
      complaints (A: 3.74% vs B: 2.20%, P=.006) and in the outpatient complaints (A:
      0.53% vs. B: 0.34%, P=.005). It could also be shown that there was a continuous
      significant correlation in the parallel decrease in the hospital and outpatient
      complaints (R:0.988 P<.001). CONCLUSIONS: The structural and functional change
      due to moving to a new hospital showed that the percentage of complaints made to
      the GGSD changed significantly in the period studied. Prospective multicentre
      studies are required to evaluate whether these results can be extrapolated to
      other services.

PMID- 22464283
TI  - Magical thinking in narratives of adolescent cutters.
AB  - Adolescents sometimes cut themselves to relieve distress; however, the mechanism
      is unknown. Previous studies have linked self-injury to deficits in processing
      emotions symbolically through language. To investigate expressive language of
      adolescent cutters, the authors analyzed 100 narratives posted on the Internet.
      Most narratives (n = 66) displayed idiosyncratic use of language indicating poor
      differentiation between the real and the symbolic, such as blood substituting for
      negative emotions, which can then be released from the self; or emotional pain
      magically transforming into physical pain, which can then be managed. This kind
      of magical thinking correlated with cutting to relieve distress, to see blood,
      and to feel pain, but negatively correlated with complex representation of
      people, understanding social causality, and self-esteem. The results suggest that
      magical thinking represents a pre-symbolic mental state that processes and
      organizes distressing emotions through body schema. Magical thinking thus
      provides a plausible mechanism for why cutting works.

PMID- 22464284
TI  - Minimising phosphorus losses from the soil matrix.
AB  - Phosphorus loss from land, due to agricultural intensification, can impair water
      quality. The quantity lost is a function of runoff and availability, which is
      affected by inputs and the ability of the soil to retain P. Losses are
      exacerbated if surface runoff or drainage occurs soon after P inputs (e.g.
      fertiliser and/or manure and dung). Strategies to mitigate P losses depend on the
      farming system. The first step is to maintain a farm P balance (inputs-outputs)
      close to zero and the agronomic optimum. The next step is to use mitigation
      strategies in areas that lose the most P, but occupy little of the farm or
      catchment's area. Focusing on these areas, termed critical source areas, is more
      cost-effective than farm or catchment-wide strategies. However, the worry is that
      mitigation strategies may not keep pace with losses due to increasing
      intensification. Therefore, a proactive approach is needed that identifies areas
      resilient to P inputs and unlikely to lose P if land use is intensified.

PMID- 22464282
TI  - Targeting MDR in breast and lung cancer: discriminating its potential importance
      from the failure of drug resistance reversal studies.
AB  - This special issue of Drug Resistance Updates is dedicated to multidrug
      resistance protein 1 (MDR-1), 35 years after its discovery. While enormous
      progress has been made and our understanding of drug resistance has become more
      sophisticated and nuanced, after 35 years the role of MDR-1 in clinical oncology
      remains a work in progress. Despite clear in vitro evidence that P-glycoprotein
      (Pgp), encoded by MDR-1, is able to dramatically reduce drug concentrations in
      cultured cells, and that drug accumulation can be increased by small molecule
      inhibitors, clinical trials testing this paradigm have mostly failed. Some have
      argued that it is no longer worthy of study. However, repeated analyses have
      demonstrated MDR-1 expression in a tumor is a poor prognostic indicator leading
      some to conclude MDR-1 is a marker of a more aggressive phenotype, rather than a
      mechanism of drug resistance. In this review we will re-evaluate the MDR-1 story
      in light of our new understanding of molecular targeted therapy, using breast and
      lung cancer as examples. In the end we will reconcile the data available and the
      knowledge gained in support of a thesis that we understand far more than we
      realize, and that we can use this knowledge to improve future therapies.

PMID- 22464285
TI  - omega-6 lipids regulate PPAR turnover via reciprocal switch between PGC-1 alpha
      and ubiquitination.
AB  - OBJECTIVE: Dietary omega-6 lipids such as linoleic acid and its oxidized forms
      (13-HPODE OxLA) interact with peroxisome proliferator-activated receptors (PPARs)
      and elicit pro and anti-atherogenic effects in vascular cells. Ligand-dependent
      PPAR protein turnover is promoted by ubiquitination, but attenuated by binding to
      its co-activator, peroxisome proliferator-activated receptor gamma coactivator-1
      (PGC-1alpha). The objective of our study was to investigate if the dual
      atherogenic effects of omega-6 lipids are due to its regulation of PPAR turnover.
      METHODS AND RESULTS: In rat aortic smooth muscle cells (RASMCs), oxidized
      linoleic acid (OxLA) at 10-50 MUM induced and stabilized PPARalpha protein at
      earlier time points (0-4 h) but suppressed it at 12 h. Conversely, it activated
      PPARgamma protein turnover at a later time point (12 h). Pre-treatment with the
      proteasome inhibitor (MG132) prevented OxLA mediated loss of PPAR stability and
      transactivity. Co-immunoprecipitation studies indicated a ligand mediated time
      dependent reciprocal exchange of PPAR interaction between ubiquitination and PGC
      1alpha. This omega-6 lipid mediated time-dependent switch between PPAR
      degradation versus stability helped modulate the pro and anti-atherogenic effects
      of these dietary lipids. CONCLUSION: Our findings provide insights into the dual
      pro and anti-atherogenic effects of dietary omega-6 lipids on vascular cells by
      the regulation of PPAR turnover.

PMID- 22464286
TI  - Elevated level of C-reactive protein is associated with risk of prediabetes in
      Indians.
AB  - BACKGROUND: Relationship of high sensitivity C-reactive protein (hsCRP) with
      prediabetes has not been explored extensively in Indians. Here we sought to
      investigate the association of hsCRP levels with prediabetes, as represented by
      impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and the
      influence of risk factors like obesity, decreased HDL cholesterol, hypertension,
      family history of diabetes and current smoking habit on the relationship.
      METHODS: A cross-sectional study on 1726 Indians, comprising of 1276 individuals
      with normal glucose tolerance (NGT), 250 IFG and 200 IGT individuals. Subjects
      were defined according to WHO criteria based on fasting plasma and 2 h glucose
      levels. RESULTS: Median levels of hsCRP were significantly higher in IFG (2.20
      mg/l) and IGT (2.32 mg/l) compared to NGT (1.64 mg/l) subjects. Individuals with
      high risk hsCRP levels (>3 mg/l) had an odds ratio (OR) (95% confidence interval
      (CI)) of 2.60 (1.56-5.34) [P=1.3*10(-4)] for IGT after adjusting the effect of
      age, sex, medication, body mass index (BMI), waist circumference (WC) and risk
      factors like decreased high-density lipoprotein cholesterol (HDL-cholesterol),
      hypertension, family history of diabetes and current smoking. Significant
      increase in risk of IGT was found with a unit increase in natural log transformed
      hsCRP levels after adjustment for covariates [OR (95%CI)=1.57 (1.27-1.94),
      P=3.0*10(-5)]. When subjects were stratified on the basis of risk factors, we
      found stronger association of elevated hsCRP levels with risk of IFG and IGT in
      subjects having HDL-cholesterol <=50 mg/dl and with hypertension. CONCLUSIONS:
      Our study demonstrates that elevated hsCRP levels are independently associated
      with risk of IFG and IGT in Indians.

PMID- 22464287
TI  - Do large-diameter hamstring grafts in young patients prevent knee osteoarthritis
      after ACL reconstruction?

PMID- 22464288
TI  - Does ACL reconstruction lead to degenerative joint disease or does it prevent
      osteoarthritis? How to read science.

PMID- 22464289
TI  - Can the battle against tuberculosis gain from epigenetic research?
AB  - A healthy immune system needs to be highly plastic to cope with host defense and
      surveillance. What mechanisms provide this plasticity? Considering the threat of
      infectious diseases to a large part of the world's population, can these
      mechanisms possibly be of use in the ongoing battle against infectious diseases?
      Against the backdrop of the pandemic nature of tuberculosis, we discuss whether
      and how epigenetic mechanisms can shed light on our understanding of infectious
      disease, and if epigenetic marks can be employed to monitor latent infection,
      disease reactivation or treatment response.

PMID- 22464290
TI  - Ectopic pregnancy in a cesarean-section scar: the patient >6 weeks into an
      ectopic pregnancy, underwent local treatment.
AB  - Cesarean scar ectopic pregnancies may be difficult to diagnose and may result in
      uterine rupture or hysterectomy. Based on location and vascularity, especially in
      the presence of fetal cardiac activity, local treatment with transvaginal
      ultrasound-guided injection of methotrexate is an excellent option which also
      optimizes the chance for fertility preservation.

PMID- 22464291
TI  - Telephone triage of influenza-like illness during pandemic 2009 H1N1 in an
      obstetric population.
AB  - We sought to determine the safety and efficiency of a telephone-based triage
      system for influenza-like illness, during the 2009 pandemic, at our institution.
      A triage system was implemented that involved initial telephone screening by a
      provider who determined whether outpatient telephone-based care or assessment in
      a centralized evaluation unit was needed. Those who received outpatient care were
      empirically treated. Those seen in the evaluation unit were assessed for
      inpatient admission. Of the 230 women who were evaluated, 41% were treated as
      outpatients and 59% were seen in the evaluation unit. Of those treated as
      outpatients, 9% were eventually seen in the evaluation unit and only 4% were
      ultimately admitted, with a maximum hospitalization of 4 days. Of the 135
      patients initially seen in the evaluation unit, 32% were admitted and 44% had a
      positive polymerase chain reaction for respiratory pathogens. This triage system
      improved efficiency of resource utilization without incurring apparent influenza
      like illness morbidity.

PMID- 22464292
TI  - Stem cells in gynecology.
AB  - Stem cell based therapies hold promise for the obstetrician and gynecologist.
      This article reviews the history of stem cells and some of their current
      applications in gynecology. Currently, mesenchymal and muscle-derived stem cells
      are being explored for the treatment of urinary and anal incontinence. Potential
      stem cell treatments include fistula repair, vaginal tissue engineering, and
      graft material enhancement. Published animal and human pilot studies demonstrate
      improved histologic and functional outcomes in those receiving stem cells.
      Transplanted cells may improve function by local engraftment, trophic factors, or
      modulation of inflammation. Further clinical and safety studies are needed before
      clinical application.

PMID- 22464293
TI  - Affiliative behavior attenuates stress responses of GI tract via up-regulating
      hypothalamic oxytocin expression.
AB  - Hypothalamic oxytocin (OXT) has stress-attenuating effects. Social interaction in
      a positive environment continuously activates OXT release system. We have
      recently shown that pair housing restores delayed gastric emptying following
      chronic heterotypic stress, via up-regulation of OXT mRNA expression in rats. We
      tested the hypothesis that affiliative behavior attenuates stress responses via
      upregulating OXT expression. Adult male SD rats were divided into two groups: the
      rat with a stressed partner (RSP) and the rat with a non-stressed partner (RNSP).
      RSPs were pair housed with a partner that received different types of stress for
      7 consecutive days (chronic heterotypic stress). RNSPs were pair housed with a
      partner who did not receive any stress. After each stress loading, the rats were
      returned to their home cages and the behaviors of RSPs and RNSPs toward their
      partners were videotaped. After the study completion, RSPs and RNSPs were loaded
      with acute restraint stress. Then, gastric emptying and colonic transit were
      measured. Corticotropin releasing factor (CRF) and OXT expression in the
      paraventricular nucleus (PVN) were evaluated by real time RT-PCR and
      immunohistochemistry. The time of affiliative behaviors toward their partners was
      increased in RSPs, compared to that of RNSPs. Delayed gastric emptying and
      accelerated colonic transit induced by acute restraint stress were significantly
      attenuated in RSPs, compared to RNSPs. CRF expression was reduced, while OXT
      expression was increased in RSPs in response to acute stress, compared to
      controls. It is suggested that affiliative behaviors may upregulate hypothalamic
      OXT expression, which in turn attenuates stress responses.

PMID- 22464294
TI  - [The social and cultural dimension of prevention: considerations on the
      collective and individual benefits of prevention].

PMID- 22464295
TI  - Acute ischemic stroke. Introduction.

PMID- 22464296
TI  - The natural history of acute ischemic stroke due to intracranial large-vessel
      occlusion: what do we know?
AB  - Acute ischemic stroke (AIS) is an important public health issue with major impact
      on not only patients and families but also on the society as well. Among patients
      who suffer from AIS, those who have the event due to large-vessel occlusion are
      thought to have the worse outcome. Because most of the effort in endovascular
      treatment of AIS is aimed toward this type of stroke, it is important to
      understand its natural history. The goal of this manuscript was to briefly
      discuss the natural history of AIS due to large-vessel occlusion based on recent
      literature.

PMID- 22464297
TI  - Elements of a stroke center.
AB  - The past decade has ushered in a refined understanding of--and commitment to-
      objective evidence-based practice of stroke management. Responding to the need
      for universal protocol-driven guidelines for stroke care, the Brain Attack
      Coalition published consensus statements with recommendations for primary stroke
      centers (Alberts MJ, et al, JAMA 283:3102-3109, 2000) and comprehensive stroke
      centers (Alberts MJ, et al, Stroke 36:1597-1616, 2005) in 2000 and 2005,
      respectively. These benchmark publications helped to define a new "standard of
      care" for stroke patients and laid the groundwork to establish formal
      certification for stroke centers. Although large randomized controlled trials
      evaluating the efficacy of these guidelines are currently underway, several
      recent reports suggest that stroke center certification may improve outcomes in
      patients with acute ischemic stroke. In this article, the authors briefly discuss
      the status of stroke center certification and the evolution of stroke systems of
      care.

PMID- 22464298
TI  - Current indications and results of thrombolysis by intravenous recombinant tissue
      plasminogen activator.
AB  - A number of landmark trials have proven the efficacy of thrombolysis by
      intravenous recombinant tissue plasminogen activator in the acute phase of the
      ischemic stroke. Despite the recently extended time window of 4.5 hours, the
      number of people who are being treated in most centers is low. Several reasons
      seem to account for this, including poor recognition of symptoms, delays in
      emergency transport, low levels of public awareness, or age limits originally
      imposed by drug regulatory rules. Trials are ongoing to possibly extend the
      indications to the treatment. A major effort is to extend the time window by
      bridging the treatment with neuroprotective approaches, or by identifying
      subgroups that may particularly benefit from recanalization and reperfusion.
      Procedures using ultrasounds or alternative intravenous compounds are also being
      investigated with promising results.

PMID- 22464299
TI  - Neuroimaging in acute stroke: choosing the right patient for neurointervention.
AB  - Although the non-contrast computed tomography head continues as the sole
      mandatory imaging technique before intravenous thrombolysis, the increased
      availability of advanced infarct/penumbral imaging techniques and confidence in
      their use have led many to adopt them into routine practice--most particularly
      before intra-arterial interventions. Computed tomography versus magnetic
      resonance-based routes to imaging the cerebral vasculature, cell death, and
      parenchymal perfusion have differing advantages in terms of speed, availability,
      exposures to contrast and radiation, sensitivity, and resolution. Continued
      refinement and future developments, such as the ability to quantitate perfusion,
      promise to lead to tailored treatment protocols that respect the individual
      variations in anatomy, physiology, and pathology. This should lead both to an
      extension of treatment to patients currently excluded by rigid time windows and
      the avoidance of futile therapies and their associated morbidities.

PMID- 22464300
TI  - Endovascular treatment of acute ischemic stroke: current indications.
AB  - Endovascular stroke therapy is an effective means of achieving reperfusion in
      stroke patients with proximal cerebral artery occlusions. However, current
      guideline recommendations express uncertainty regarding the clinical efficacy of
      catheter-based treatments, given the lack of supportive trial data. A critical
      problem is that it remains unclear which patients will benefit from endovascular
      therapy. As such, patient selection is likely highly variable in clinical
      practice. This article will review the existing data to discuss the clinical and
      imaging factors that are relevant to patient outcomes, and which may be used to
      guide endovascular treatment decisions. Anterior circulation strokes represent
      the primary focus of this review.

PMID- 22464301
TI  - Intra-arterial thrombolysis: tissue plasminogen activator and other thrombolytic
      agents.
AB  - Recanalization rates with the administration of intravenous tissue plasminogen
      activator in acute ischemic stroke are low. Adjuvant endovascular techniques that
      achieve recanalization by direct intra-arterial (IA) delivery of thrombolytics,
      mechanical clot retrieval, clot aspiration, and stenting may complement
      intravenous pharmacotherapy. IA thrombolytics can be administered within 6 hours
      of symptom onset in anterior circulation strokes and within 24 hours in posterior
      circulation strokes. This review describes the indications, patient selection,
      and technique for IA administration of thrombolytics.

PMID- 22464302
TI  - Acute stroke: techniques and results with the Merci retriever.
AB  - Acute ischemic stroke is one of the most prominent causes of death and disability
      in the modern world. Despite extensive research, the only Food and Drug
      Administration-approved pharmacologic treatment is intravenous recombinant tissue
      plasminogen activator (rt-PA). Although reperfusion remains the most robust
      predictor of clinical outcome, rt-PA has been linked to low recanalization rates
      in large-vessel occlusion. Endovascular techniques have been developed over past
      decade with several theoretic advantages over intravenous rt-PA alone, including
      longer treatment windows and higher recanalization rates in large-vessel
      occlusions. The Merci retriever thrombectomy device was approved by the Food and
      Drug Administration in 2004 for removing thrombus in acute ischemic stroke. In
      this article, we review the indications for acute stroke endovascular treatment
      with the Merci retriever as well as the involved techniques and the results of
      research studies.

PMID- 22464303
TI  - Techniques and results--penumbra aspiration catheter.
AB  - The Penumbra System is an endovascular mechanical thrombectomy device that uses
      continuous aspiration to perform recanalization of occluded intracranial vessels.
      The objective of this article was to provide a comprehensive overview of the data
      on technical and functional outcome so far published for aspiration thrombectomy
      and resume techniques that can be used to optimize functionality of the Penumbra
      System. We focus on existing clinical data as well as our institutional
      experience and techniques.

PMID- 22464304
TI  - Techniques and results: intracranial stenting.
AB  - Recanalization rates with conventional pharmacologic thrombolysis and
      thrombectomy devices in the treatment of large-vessel occlusions are low.
      Moreover, these patients do not have favorable clinical outcomes. Better
      recanalization devices and approaches are needed. In this review, we describe
      current stents used in the intracranial circulation and their application in the
      treatment of acute ischemic stroke due to large-vessel occlusion.

PMID- 22464305
TI  - Use of stentrievers in acute stroke: tips, tricks, and current results.
AB  - Stentrievers are stent-like devices used in the treatment of acute ischemic
      stroke. They have demonstrated efficacy in restoring the intracranial blood flow
      with low procedural times. This article is a synopsis of the available devices
      and different techniques. An extensive review of the literature summarizing all
      the data that have been published demonstrating their clinical impact and
      complications is also presented.

PMID- 22464306
TI  - Acute stroke: postprocedural care and management of complications.
AB  - Endovascular treatment for acute ischemic stroke is an important alternative to
      thrombolysis with recombinant tissue plasminogen activator (rt-PA) for patients
      who present beyond the thrombolysis time window, those who are ineligible for rt
      PA, or those who do not improve after intravenous rt-PA. These patients generally
      require special attention in the postprocedural period because, although not
      frequent, complications of endovascular procedures in acute ischemic stroke have
      the potential to be devastating. Neurocritical care is essential to reduce and
      appropriately treat complications after endovascular procedures.
      Neurointensivists and neurocritical care nurses are experts in both critical care
      and neurologic disorders and have special training to recognize early
      physiological derangements in patients presenting with acute stroke. Close
      attention to the serial neurological examination, blood pressure control,
      adequate management of glucose, temperature, and immediate identification of
      complications such as reocclusion and hemorrhagic transformation are key elements
      that exemplify the importance of postprocedural neurocritical care in acute
      ischemic stroke.

PMID- 22464307
TI  - Past, present, and future perspectives on the endovascular treatment of acute
      ischemic stroke.
AB  - Interventional neuroradiology plays a continuously expanding and exciting role in
      the treatment of acute stroke, as evidenced by the development of several
      important advances, including the advent of multiple new devices and therapies.
      Furthermore, guidelines regarding endovascular interventions in the setting of
      acute stroke have been developed and used. In addition to technological advances,
      the field of pharmacology in the setting of acute stroke is constantly evolving.
      In a rapidly expanding field, we aim to review significant recent advances
      related to the endovascular treatment of stroke as well as provide perspective
      for future directions.

PMID- 22464308
TI  - Prostate cancer epidemic in sight?

PMID- 22464309
TI  - Re: Jens J. Rassweiler, Michael Muller, Markus Fangerau, et al. iPad-assisted
      percutaneous access to the kidney using marker-based navigation: initial clinical
      experience. Eur Urol 2012;61:628-31.

PMID- 22464310
TI  - OnabotulinumtoxinA improves health-related quality of life in patients with
      urinary incontinence due to idiopathic overactive bladder: a 36-week, double
      blind, placebo-controlled, randomized, dose-ranging trial.
AB  - BACKGROUND: Patients with urgency urinary incontinence (UUI) due to overactive
      bladder (OAB) refractory to oral antimuscarinics have limited therapeutic
      options. OnabotulinumtoxinA appears to be an effective new treatment. OBJECTIVE:
      Assess disease-specific quality-of-life outcomes and general health-related
      quality-of-life (HRQOL) outcomes following treatment with onabotulinumtoxinA in
      patients with idiopathic OAB and UUI inadequately managed with antimuscarinics.
      DESIGN, SETTING, AND PARTICIPANTS: A phase 2, randomized, double-blind, placebo
      controlled, dose-ranging study conducted at 40 sites from July 2005 to June 2008
      with 313 patients (288 females) with idiopathic OAB experiencing eight or more
      UUI episodes per week and eight or more micturitions per day at baseline, with
      follow-up of 36 wk. INTERVENTION: Intradetrusor onabotulinumtoxinA (50 U, 100 U,
      150 U, 200 U, or 300 U) or placebo. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: HRQOL was assessed using the urinary Incontinence-Specific Quality-of
      Life Instrument (I-QOL), the King's Health Questionnaire (KHQ) symptom component,
      and the Medical Outcomes Study 36-Item Short-Form Health Survey. Descriptive
      statistics were used for absolute scores/changes from baseline. Within-group
      changes from baseline were assessed using paired t tests. Change from baseline
      for each onabotulinumtoxinA group compared with placebo was analyzed using an
      analysis of covariance model. RESULTS AND LIMITATIONS: OnabotulinumtoxinA
      treatment at doses>=100 U produced significantly greater improvements than
      placebo in the I-QOL total and subscale scores at all follow-up visits from week
      2 through week 24 (p<0.05). OnabotulinumtoxinA doses>=100 U produced
      significantly greater improvements than placebo in the KHQ symptom score at a
      majority of follow-up visits. HRQOL instruments demonstrated low to moderate
      correlations (Spearman correlation range: 0.01-0.51) with the symptoms of UUI
      recorded using daily diary data, with I-QOL demonstrating the highest
      correlations. A study limitation was that certain quality-of-life measures were
      exploratory and not validated. CONCLUSIONS: A single onabotulinumtoxinA treatment
      with doses>=100 U resulted in statistically significant and clinically meaningful
      improvement in HRQOL by week 2 compared with placebo, and this improvement was
      sustained for <=36 wk in patients with idiopathic OAB and UUI who were
      inadequately managed by oral antimuscarinics. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00168454.

PMID- 22464311
TI  - The contemporary role of chemotherapy for advanced testis cancer: a systematic
      review of the literature.
AB  - CONTEXT: Germ cell tumours (GCTs) of the testis are the most common cancer in
      young men; they are also one of the most curable cancers. Standard treatment of
      metastatic GCTs has evolved on the basis of randomised trials and prognostic
      factors. OBJECTIVE: This review summarises the evolving role of chemotherapy in
      the treatment of previously treated and untreated patients with metastatic GCTs
      and outlines the current standard treatment. EVIDENCE ACQUISITION: Randomised and
      nonrandomised trials of first-line, salvage, and palliative therapy were
      reviewed. EVIDENCE SYNTHESIS: Three cycles of standard bleomycin, etoposide, and
      platinum (BEP) can be considered the gold-standard treatment in good-risk
      patients, and four cycles of the same combination can result in cure in
      approximately 80% of intermediate-risk and 50% of poor-risk patients. The routine
      use of high-dose chemotherapy in patients with intermediate- or poor-prognosis
      GCT has not improved treatment outcome, but the role of tumour marker decline
      during the first cycles may provide useful prognostic information. Prognostic
      variables in patients who experience treatment failure after cisplatin-based
      chemotherapy can be used to guide salvage strategies, and many new drugs or
      combinations have shown activity in this setting. Patients and physicians should
      be aware of the risk of short- and long-term toxicity of treatments, and
      guidelines for screening and prevention of this risk should be established.
      CONCLUSIONS: A risk-based strategy offers the best chance of cure, even in
      patients with refractory GCT.

PMID- 22464312
TI  - The role of care home fees in the public costs and distributional effects of
      potential reforms to care home funding for older people in England.
AB  - In England, Local Authorities (LAs) contribute to the care home fees of two
      thirds of care home residents aged 65+ who pass a means test. LAs typically pay
      fees below those faced by residents excluded from state support. Most proposals
      for reform of the means test would increase the proportion of residents entitled
      to state support. If care homes receive the LA fee for more residents, they might
      increase fees for any remaining self-funders. Alternatively, the LA fee might
      have to rise. We use two linked simulation models to examine how alternative
      assumptions on post-reform fees affect projected public costs and financial gains
      to residents of three potential reforms to the means test. Raising the LA fee
      rate to maintain income per resident would increase the projected public cost of
      the reforms by between 22% and 72% in the base year. It would reduce the average
      gain to care home residents by between 8% and 12%. Raising post-reform fees for
      remaining self-funders or requiring pre-reform self-funders to meet the
      difference between the LA and self-funder fees, reduces the gains to residents by
      28-37%. For one reform, residents in the highest income quintile would face
      losses if the self-funder fee rises.

PMID- 22464314
TI  - Treatment of systemic sclerosis complications: what to use when first-line
      treatment fails--a consensus of systemic sclerosis experts.
AB  - OBJECTIVES: There is a need for standardization in systemic sclerosis (SSc)
      management. METHODS: SSc experts (n = 117) were sent 3 surveys to gain consensus
      for SSc management. RESULTS: First-line therapy for scleroderma renal crisis
      (SRC) was an angiotensin-converting enzyme inhibitor (ACEi). For SRC there were
      not many differences between treating mild or severe SRC. In general, Second-line
      was to add either a calcium channel blocker (CCB) or angiotensin receptor blocker
      (ARB) and then an alpha-blocker (66% agreed). Endothelin receptor agonists (ERAs)
      were the first treatment in mild pulmonary arterial hypertension (PAH) (72%),
      followed by adding a phosphodiesterase-5 inhibitor (PDE5i) (77%) and then a
      prostanoid (73%). For severe PAH, initial treatment was 1 of the following: a
      prostanoid (49%), combination of a ERA and a PDE5i (18%), or combination of a ERA
      and a prostanoid (16%) (71% agreed). For mild Raynaud's phenomenon (RF), after a
      CCB and adding a PDE5i (35%), trying an ARB (32%) and finally a prostanoid (23%)
      was suggested. For more severe RF, 54% agreed on adding a PDE5i (45%) or
      prostanoid (32%) to a CCB. In the prevention of digital ulcers (DU), initial
      treatment was a CCB (73%), then adding a PDE5i, then use of a ERA, and then a
      prostanoid (44% agreed). In interstitial lung disease/pulmonary fibrosis, for
      induction, usually intravenous cyclophosphamide and mycophenolate mofetil (MMF)
      or azathioprine were chosen. For maintenance, MMF was chosen by three-fourths
      (56% agreed). For gastroesophageal reflux disease, >50% would exceed the maximum
      recommended proton pump inhibitor dose if required (72% agreed). For skin
      involvement after methotrexate, MMF was usually chosen (37% agreement). For SSC
      related inflammatory arthritis, methotrexate therapy (60%) was followed by adding
      corticosteroids (37%) or hydroxychloroquine (31%) (62% agreed). CONCLUSIONS:
      Discrepancies in drug choices occurred in treatment after first line in SSc. Not
      all algorithms had good agreement. This study provides some guidance for SSc
      management.

PMID- 22464315
TI  - High resolution tumor targeting in living mice by means of multispectral
      optoacoustic tomography.
AB  - BACKGROUND: Tumor targeting is of high clinical and biological relevance, and
      major efforts have been made to develop molecular imaging technologies for
      visualization of the disease markers in tissue. Of particular interest is
      apoptosis which has a profound role within tumor development and has significant
      effect on cancer malignancy. METHODS: Herein, we report on targeting of
      phosphatidylserine-exposing cells within live tumor allograft models using a
      synthetic near infrared zinc(II)-dipicolylamine probe. Visualization of the probe
      biodistribution is performed with whole body multispectral optoacoustic
      tomography (MSOT) system and subsequently compared to results attained by planar
      and tomographic fluorescence imaging systems. RESULTS: Compared to whole body
      optical visualization methods, MSOT attains remarkably better imaging capacity by
      delivering high-resolution scans of both disease morphology and molecular
      function in real time. Enhanced resolution of MSOT clearly showed that the probe
      mainly localizes in the vessels surrounding the tumor, suggesting that its tumor
      selectivity is gained by targeting the phosphatidylserine exposed on the surface
      of tumor vessels. CONCLUSIONS: The current study demonstrates the high potential
      of MSOT to broadly impact the fields of tumor diagnostics and preclinical drug
      development.

PMID- 22464316
TI  - The joy of six: how to control your crossovers.
AB  - Meiotic cells tightly regulate the number and distribution of crossovers to
      promote accurate chromosome segregation. Yokoo and colleagues uncover a metazoan
      specific, cyclin-like protein that is crucial for crossover formation. They
      utilize this protein's unique properties to explore a remarkable example of
      biological numerology, whereby nearly every meiotic cell in C. elegans makes
      precisely six crossovers, one for each of its six chromosome pairs.

PMID- 22464317
TI  - A molecular doorstop ensures a trickle through translational repression.
AB  - Switching mRNA translation off and on is central to regulated gene expression,
      but what mechanisms moderate the extent of switch-off? Yao et al. describe how
      basal expression from interferon-gamma-induced transcripts is maintained during
      mRNA-specific translational repression. This antagonistic mechanism utilizes a
      truncated RNA-binding factor generated by a unique alternative polyadenylation
      event.

PMID- 22464318
TI  - Deconstructing the complexity of a microenvironmental niche.
AB  - Cells acquire their fate in vivo in the context of a complex microenvironmental
      "niche" comprised of heterologous cell types, signaling molecules, extracellular
      matrix, biophysical forces, and metabolic substrates. Now Calderon and Boehm
      report the "refunctionalization" of a defective thymic epithelial niche, offering
      insights into how signaling molecules may be hierarchically organized to direct
      differentiation outcomes.

PMID- 22464319
TI  - The virtues of youth and maturity (in dentate granule cells).
AB  - How does adult neurogenesis contribute to memory? Nakashiba and colleagues
      generated mutant mice in which synaptic output from older hippocampal granule
      cells was specifically blocked. Experiments with these mice reveal an unpredicted
      age-dependent specialization of function, demonstrating that recently born cells
      support pattern separation, whereas older cells support pattern completion.

PMID- 22464320
TI  - COPII vesicles get supersized by ubiquitin.
AB  - Some proteins are too big to fit into conventional COPII-coated vesicles, which
      raises the question of how large cargo, such as procollagen fibrils, are exported
      from the endoplasmic reticulum. Jin et al. (2012) in Nature now report that the
      creation of oversized vesicles is facilitated by the ubiquitination of the COPII
      component Sec31p.

PMID- 22464321
TI  - MYC on the path to cancer.
AB  - The MYC oncogene contributes to the genesis of many human cancers. Recent
      insights into its expression and function have led to therapeutic opportunities.
      MYC's activation by bromodomain proteins could be inhibited by drug-like
      molecules, resulting in tumor inhibition in vivo. Tumor growth can also be curbed
      by pharmacologically uncoupling bioenergetic pathways involving glucose or
      glutamine metabolism from Myc-induced cellular biomass accumulation. Other
      approaches to halt Myc on the path to cancer involve targeting Myc-Max
      dimerization or Myc-induced microRNA expression. Here the richness of our
      understanding of MYC is reviewed, highlighting new biological insights and
      opportunities for cancer therapies.

PMID- 22464323
TI  - The HIF signaling pathway in osteoblasts directly modulates erythropoiesis
      through the production of EPO.
AB  - Osteoblasts are an important component of the hematopoietic microenvironment in
      bone. However, the mechanisms by which osteoblasts control hematopoiesis remain
      unknown. We show that augmented HIF signaling in osteoprogenitors results in HSC
      niche expansion associated with selective expansion of the erythroid lineage.
      Increased red blood cell production occurred in an EPO-dependent manner with
      increased EPO expression in bone and suppressed EPO expression in the kidney. In
      contrast, inactivation of HIF in osteoprogenitors reduced EPO expression in bone.
      Importantly, augmented HIF activity in osteoprogenitors protected mice from
      stress-induced anemia. Pharmacologic or genetic inhibition of prolyl
      hydroxylases1/2/3 in osteoprogenitors elevated EPO expression in bone and
      increased hematocrit. These data reveal an unexpected role for osteoblasts in the
      production of EPO and modulation of erythropoiesis. Furthermore, these studies
      demonstrate a molecular role for osteoblastic PHD/VHL/HIF signaling that can be
      targeted to elevate both HSCs and erythroid progenitors in the local
      hematopoietic microenvironment.

PMID- 22464322
TI  - Malignant glioma: lessons from genomics, mouse models, and stem cells.
AB  - Eighty percent of malignant tumors that develop in the central nervous system are
      malignant gliomas, which are essentially incurable. Here, we discuss how recent
      sequencing studies are identifying unexpected drivers of gliomagenesis, including
      mutations in isocitrate dehydrogenase 1 and the NF-kappaB pathway, and how genome
      wide analyses are reshaping the classification schemes for tumors and enhancing
      prognostic value of molecular markers. We discuss the controversies surrounding
      glioma stem cells and explore how the integration of new molecular data allows
      for the generation of more informative animal models to advance our knowledge of
      glioma's origin, progression, and treatment.

PMID- 22464324
TI  - COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps
      governing meiotic crossovers.
AB  - Crossovers (COs) between homologous chromosomes ensure their faithful segregation
      during meiosis. We identify C. elegans COSA-1, a cyclin-related protein conserved
      in metazoa, as a key component required to convert meiotic double-strand breaks
      (DSBs) into COs. During late meiotic prophase, COSA-1 localizes to foci that
      correspond to the single CO site on each homolog pair and indicate sites of
      eventual concentration of other conserved CO proteins. Chromosomes gain and lose
      competence to load CO proteins during meiotic progression, with competence to
      load COSA-1 requiring prior licensing. Our data further suggest a self
      reinforcing mechanism maintaining CO designation. Modeling of a nonlinear dose
      response relationship between IR-induced DSBs and COSA-1 foci reveals efficient
      conversion of DSBs into COs when DSBs are limiting and a robust capacity to limit
      cytologically differentiated CO sites when DSBs are in excess. COSA-1 foci serve
      as a unique live cell readout for investigating CO formation and CO interference.

PMID- 22464325
TI  - Membrane fission is promoted by insertion of amphipathic helices and is
      restricted by crescent BAR domains.
AB  - Shallow hydrophobic insertions and crescent-shaped BAR scaffolds promote membrane
      curvature. Here, we investigate membrane fission by shallow hydrophobic
      insertions quantitatively and mechanistically. We provide evidence that membrane
      insertion of the ENTH domain of epsin leads to liposome vesiculation, and that
      epsin is required for clathrin-coated vesicle budding in cells. We also show that
      BAR-domain scaffolds from endophilin, amphiphysin, GRAF, and beta2-centaurin
      limit membrane fission driven by hydrophobic insertions. A quantitative assay for
      vesiculation reveals an antagonistic relationship between amphipathic helices and
      scaffolds of N-BAR domains in fission. The extent of vesiculation by these
      proteins and vesicle size depend on the number and length of amphipathic helices
      per BAR domain, in accord with theoretical considerations. This fission mechanism
      gives a new framework for understanding membrane scission in the absence of
      mechanoenzymes such as dynamin and suggests how Arf and Sar proteins work in
      vesicle scission.

PMID- 22464326
TI  - Structural basis of membrane bending by the N-BAR protein endophilin.
AB  - Functioning as key players in cellular regulation of membrane curvature, BAR
      domain proteins bend bilayers and recruit interaction partners through poorly
      understood mechanisms. Using electron cryomicroscopy, we present reconstructions
      of full-length endophilin and its N-terminal N-BAR domain in their membrane-bound
      state. Endophilin lattices expose large areas of membrane surface and are held
      together by promiscuous interactions between endophilin's amphipathic N-terminal
      helices. Coarse-grained molecular dynamics simulations reveal that endophilin
      lattices are highly dynamic and that the N-terminal helices are required for
      formation of a stable and regular scaffold. Furthermore, endophilin accommodates
      different curvatures through a quantized addition or removal of endophilin
      dimers, which in some cases causes dimerization of endophilin's SH3 domains,
      suggesting that the spatial presentation of SH3 domains, rather than affinity,
      governs the recruitment of downstream interaction partners.

PMID- 22464327
TI  - The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that
      functions as a tumor suppressor.
AB  - Lineage mapping has identified both proliferative and quiescent intestinal stem
      cells, but the molecular circuitry controlling stem cell quiescence is
      incompletely understood. By lineage mapping, we show Lrig1, a pan-ErbB inhibitor,
      marks predominately noncycling, long-lived stem cells that are located at the
      crypt base and that, upon injury, proliferate and divide to replenish damaged
      crypts. Transcriptome profiling of Lrig1(+) colonic stem cells differs markedly
      from the profiling of highly proliferative, Lgr5(+) colonic stem cells; genes
      upregulated in the Lrig1(+) population include those involved in cell cycle
      repression and response to oxidative damage. Loss of Apc in Lrig1(+) cells leads
      to intestinal adenomas, and genetic ablation of Lrig1 results in heightened ErbB1
      3 expression and duodenal adenomas. These results shed light on the relationship
      between proliferative and quiescent intestinal stem cells and support a model in
      which intestinal stem cell quiescence is maintained by calibrated ErbB signaling
      with loss of a negative regulator predisposing to neoplasia.

PMID- 22464328
TI  - Synergistic, context-dependent, and hierarchical functions of epithelial
      components in thymic microenvironments.
AB  - Specialized niche environments specify and maintain stem and progenitor cells,
      but little is known about the identities and functional interactions of niche
      components in vivo. Here, we describe a modular system for the generation of
      artificial thymopoietic environments in the mouse embryo. Thymic epithelium that
      lacks hematopoietic function but is physiologically accessible for hematopoietic
      progenitor cells is functionalized by individual and combinatorial expression of
      four factors, the chemokines Ccl25 and Cxcl12, the cytokine Scf, and the Notch
      ligand DLL4. The distinct phenotypes and variable numbers of hematopoietic cells
      in the resulting epithelial environments reveal synergistic, context-dependent,
      and hierarchical interactions among effector molecules. The surprisingly simple
      rules determining hematopoietic properties enable the in vivo engineering of
      artificial environments conducive to the presence of distinct myeloid or T or B
      lymphoid lineage precursors; moreover, synthetic environments facilitate the
      procurement of physiological progenitor cell types for analytical purposes and
      future therapeutic applications.

PMID- 22464329
TI  - Wnt signaling regulates acetylcholine receptor translocation and synaptic
      plasticity in the adult nervous system.
AB  - The adult nervous system is plastic, allowing us to learn, remember, and forget.
      Experience-dependent plasticity occurs at synapses--the specialized points of
      contact between neurons where signaling occurs. However, the mechanisms that
      regulate the strength of synaptic signaling are not well understood. Here, we
      define a Wnt-signaling pathway that modifies synaptic strength in the adult
      nervous system by regulating the translocation of one class of acetylcholine
      receptors (AChRs) to synapses. In Caenorhabditis elegans, we show that mutations
      in CWN-2 (Wnt ligand), LIN-17 (Frizzled), CAM-1 (Ror receptor tyrosine kinase),
      or the downstream effector DSH-1 (disheveled) result in similar subsynaptic
      accumulations of ACR-16/alpha7 AChRs, a consequent reduction in synaptic current,
      and predictable behavioral defects. Photoconversion experiments revealed
      defective translocation of ACR-16/alpha7 to synapses in Wnt-signaling mutants.
      Using optogenetic nerve stimulation, we demonstrate activity-dependent synaptic
      plasticity and its dependence on ACR-16/alpha7 translocation mediated by Wnt
      signaling via LIN-17/CAM-1 heteromeric receptors.

PMID- 22464330
TI  - A role for tRNA modifications in genome structure and codon usage.
AB  - Transfer RNA (tRNA) gene content is a differentiating feature of genomes that
      contributes to the efficiency of the translational apparatus, but the principles
      shaping tRNA gene copy number and codon composition are poorly understood. Here,
      we report that the emergence of two specific tRNA modifications shaped the
      structure and composition of all extant genomes. Through the analysis of more
      than 500 genomes, we identify two kingdom-specific tRNA modifications as major
      contributors that separated archaeal, bacterial, and eukaryal genomes in terms of
      their tRNA gene composition. We show that, contrary to prior observations,
      genomic codon usage and tRNA gene frequencies correlate in all kingdoms if these
      two modifications are taken into account and that presence or absence of these
      modifications explains patterns of gene expression observed in previous studies.
      Finally, we experimentally demonstrate that human gene expression levels
      correlate well with genomic codon composition if these identified modifications
      are considered.

PMID- 22464333
TI  - Retraction notice to: The chromatin-remodeling complex WINAC targets a nuclear
      receptor to promoters and is impaired in Williams syndrome.

PMID- 22464332
TI  - Proline isomer-specific antibodies reveal the early pathogenic tau conformation
      in Alzheimer's disease.
AB  - cis-trans isomerization of proteins phosphorylated by proline-directed kinases is
      proposed to control numerous signaling molecules and is implicated in the
      pathogenesis of Alzheimer's and other diseases. However, there is no direct
      evidence for the existence of cis-trans protein isomers in vivo or for their
      conformation-specific function or regulation. Here we develop peptide chemistries
      that allow the generation of cis- and trans-specific antibodies and use them to
      raise antibodies specific for isomers of phosphorylated tau. cis, but not trans,
      p-tau appears early in the brains of humans with mild cognitive impairment,
      accumulates exclusively in degenerated neurons, and localizes to dystrophic
      neurites during Alzheimer's progression. Unlike trans p-tau, the cis isomer
      cannot promote microtubule assembly, is more resistant to dephosphorylation and
      degradation, and is more prone to aggregation. Pin1 converts cis to trans p-tau
      to prevent Alzheimer's tau pathology. Isomer-specific antibodies and vaccines may
      therefore have value for the early diagnosis and treatment of Alzheimer's
      disease.

PMID- 22464334
TI  - SnapShot: Lung cancer models.

PMID- 22464331
TI  - Histone recognition and large-scale structural analysis of the human bromodomain
      family.
AB  - Bromodomains (BRDs) are protein interaction modules that specifically recognize
      epsilon-N-lysine acetylation motifs, a key event in the reading process of
      epigenetic marks. The 61 BRDs in the human genome cluster into eight families
      based on structure/sequence similarity. Here, we present 29 high-resolution
      crystal structures, covering all BRD families. Comprehensive crossfamily
      structural analysis identifies conserved and family-specific structural features
      that are necessary for specific acetylation-dependent substrate recognition.
      Screening of more than 30 representative BRDs against systematic histone-peptide
      arrays identifies new BRD substrates and reveals a strong influence of flanking
      posttranslational modifications, such as acetylation and phosphorylation,
      suggesting that BRDs recognize combinations of marks rather than singly
      acetylated sequences. We further uncovered a structural mechanism for the
      simultaneous binding and recognition of diverse diacetyl-containing peptides by
      BRD4. These data provide a foundation for structure-based drug design of specific
      inhibitors for this emerging target family.

PMID- 22464335
TI  - In vivo imaging of cumulus-oocyte-complexes and small ovarian follicles in cattle
      using ultrasonic biomicroscopy.
AB  - The objectives of this study were to: (1) evaluate the feasibility of ultrasonic
      biomicroscopy (UBM) for imaging ovarian follicles in vivo in cows and heifers,
      (2) compare the transvaginal to the transrectal approach, (3) compare the number
      of follicles detected by UBM to conventional ultrasonography (US), and (4)
      identify cumulus-oocyte-complexes (COC) within follicles by UBM. Mature cows
      (n=5) and peri-pubertal heifers (n=5) were examined once using conventional B
      mode US (Aloka 900) with a 7.5 MHz transrectal, and a 5 MHz transvaginal
      transducers. A second series of examinations was performed using UBM
      (Visualsonics Vevo 660) equipped with a 30 MHz transrectal and a 40 MHz
      transvaginal transducer. A three- to four-fold increase in the number of small
      follicles (<3 mm) was detected using the transvaginal approach with UBM compared
      to conventional US in both heifers (32.4 +/- 4.24 compared to 7.2 +/- 1.4;
      P<0.0001) and cows (35.0 +/- 13.8 compared to 10.7 +/- 7.5; P=0.0013). However,
      fewer follicles (all sizes combined) were detected using the transrectal approach
      with UBM compared to conventional US in both heifers (8.6 +/- 5.6 compared to
      17.6 +/- 4.9; P=0.02) and cows (5.3 +/- 6.1 compared to 20.3 +/- 7; P=0.04). In
      heifers, COC-like structures were identified in 39 of 202 (19.3%) follicles
      examined. In conclusion, UBM using a transvaginal approach is feasible and may be
      used for in vivo assessment of early antral follicles as small as 0.4 mm, and COC
      within follicles.

PMID- 22464336
TI  - Evaluation of duck egg yolk for the cryopreservation of Nili-Ravi buffalo bull
      semen.
AB  - This study was carried out to investigate if the substitution of chicken egg yolk
      (CEY) with duck egg yolk (DEY) in extenders can improve the quality of frozen
      thawed semen of Nili-Ravi buffalo bulls and to study if reducing DEY level in
      extender affects the freezability results. Thirty semen samples collected from
      three buffalo bulls were diluted in extenders A, B, C, D and E containing tris,
      citric acid, fructose, egg yolk, glycerol and antibiotics. Extender A contained
      20% CEY (control), while extenders B, C, D and E contained 5, 10, 15 and 20% DEY,
      respectively. After freezing and storage for 24h in liquid nitrogen, samples were
      evaluated for post-thaw quality. The post extension sperm motility did not differ
      between extenders A (control) and E (20% DEY). The same was true for post-thaw
      percentage of sperm with functional plasma membrane and percentage of sperm with
      abnormal heads or mid pieces. However, extender E showed higher (P<0.05) values
      for post-thaw sperm motility, livability and absolute index of livability of
      spermatozoa at 37  degrees C compared to extender A. Spermatozoa with abnormal
      tail were lower (P<0.05) in extender E compared to extender A. Values of these
      parameters of post-thaw semen quality were highest for extender E containing 20%
      DEY and decreased significantly with decrease in the concentration of DEY, except
      sperm abnormalities (head, mid-piece and tail) which increased with decrease in
      DEY level. These results showed that replacement of 20% CEY with 20% DEY in
      extenders significantly improved post-thaw sperm motility, livability and
      absolute index of livability of spermatozoa and reduced tail abnormalities.
      Reduction in the level of DEY in extenders from 20% adversely affected post-thaw
      semen quality of Nili-Ravi buffalo bulls.

PMID- 22464338
TI  - The cognitive profile of aripiprazole differs from that of other atypical
      antipsychotics in schizophrenia patients.
AB  - We investigated the effects of the atypical antipsychotics risperidone,
      olanzapine, and aripiprazole on the cognitive functions of Japanese patients with
      schizophrenia with respect to dosage amounts and dosing schedules. We performed a
      cross-sectional survey using the Brief Assessment of Cognition in Schizophrenia -
      Japanese Language Version (BACS-J) to evaluate the neurocognitive functions of
      101 schizophrenic patients who took the same dose of one of the three
      aforementioned antipsychotics for at least 3 months. The BACS-J composite score
      correlated negatively with the prescribed dosages of risperidone and olanzapine.
      In contrast, we did not find a correlation between the BACS-J composite score and
      the prescribed dosage of aripiprazole. Moreover, the primary scores for verbal
      learning, motor function, and attention and processing speed were significantly
      lower among the patients who were taking the prescribed dosage of risperidone.
      The scores for verbal learning and motor function were also significantly lower
      when correlated with the prescribed dosage of olanzapine. We did not find a
      correlation between any of the primary scores on the BACS-J and the prescribed
      dosage of aripiprazole. In fact, the results suggest there is no linear
      relationship between the dose of aripiprazole and cognitive impairment, which may
      be due to its unique pharmacological profile.

PMID- 22464337
TI  - Striatal activity in borderline personality disorder with comorbid intermittent
      explosive disorder: sex differences.
AB  - Borderline Personality Disorder (BPD) is associated with behavioral and emotional
      dysregulation, particularly in social contexts; however, the underlying
      pathophysiology at the level of brain function is not well understood. Previous
      studies found abnormalities in frontal cortical and limbic areas suggestive of
      poor frontal regulation of downstream brain regions. However, the striatum, which
      is closely connected with the medial frontal cortices and plays an important role
      in motivated behaviors and processing of rewarding stimuli, has been understudied
      in BPD. Here we hypothesized that, in addition to frontal dysfunction, BPD
      patients may show abnormal striatal function. In this study, 38 BPD patients with
      intermittent explosive disorder (BPD-IED) and 36 healthy controls (HC)
      participated in the Point Subtraction Aggression Paradigm (PSAP), a computer game
      played with a fictitious other player. (18)Fluoro-deoxyglucose positron emission
      tomography (FDG-PET) measured relative glucose metabolism (rGMR) within caudate
      and putamen in response to aggression-provoking and non-provoking versions of the
      PSAP. Male BPD-IED patients had significantly lower striatal rGMR than all other
      groups during both conditions, although male and female BPD-IED patients did not
      differ in clinical or behavioral measures. These sex differences suggest
      differential involvement of frontal-striatal circuits in BPD-IED, and are
      discussed in relation to striatal involvement in affective learning and social
      decision-making.

PMID- 22464339
TI  - European Group for the Study of Resistant Depression (GSRD)--where have we gone
      so far: review of clinical and genetic findings.
AB  - The primary objective of this review is to give an overview of the main findings
      of the European multicenter project "Patterns of Treatment Resistance and
      Switching Strategies in Affective Disorder", performed by the Group for the Study
      of Resistant Depression (GSRD). The aim was to study methodological issues,
      operational criteria, clinical characteristics, and genetic variables associated
      with treatment resistant depression (TRD), that is failure to reach response
      after at least two consecutive adequate antidepressant trials. The primary
      findings of clinical variables associated with treatment resistance include
      comorbid anxiety disorders as well as non-response to the first antidepressant
      received lifetime. Although there is a plethora of hints in textbooks that
      switching the mechanism of action should be obtained in case of nonresponse to
      one medication, the results of the GSRD challenge this notion by demonstrating in
      retrospective and prospective evaluations that staying on the same antidepressant
      mechanism of action for a longer time is more beneficial than switching, however,
      when switching is an option there is no benefit to switch across class. The GSRD
      candidate gene studies found that metabolism status according to cytochrome P450
      gene polymorphisms may not be helpful to predict response and remission rates to
      antidepressants. Significant associations with MDD and antidepressant treatment
      response were found for COMT SNPs. Investigating the impact of COMT on suicidal
      behaviour, we found a significant association with suicide risk in MDD patients
      not responding to antidepressant treatment, but not in responders. Further
      significant associations with treatment response phenotypes were found with BDNF,
      5HTR2A and CREB1. Additional investigated candidate genes were DTNBP1, 5HT1A,
      PTGS2, GRIK4 and GNB3.

PMID- 22464340
TI  - Conventional combination treatment versus biological treatment in methotrexate
      refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non
      blinded, parallel-group Swefot trial.
AB  - BACKGROUND: Analysis of the Swedish Farmacotherapy (Swefot) trial at 12 months
      showed that the addition of an anti-tumour-necrosis-factor agent gave an improved
      clinical outcome compared with the addition of conventional disease-modifying
      antirheumatic drugs in patients with methotrexate-refractory early rheumatoid
      arthritis. Here we report the 2 year follow-up assessment. METHODS: In this
      randomised, non-blinded, parallel-group trial, we enrolled adult patients older
      than 18 years with rheumatoid arthritis and a symptom duration of less than 1
      year from 15 rheumatology units in Sweden between December, 2002 and December,
      2006. All patients were started on methotrexate. After 3-4 months, those who
      failed treatment were randomly assigned (1:1) to group A (conventional treatment;
      additional sulfasalazine and hydroxychloroquine) or group B (biological
      treatment; additional infliximab). Randomisation was done with a computer
      generated sequence. We analysed clinical outcomes at months 18 and 24 by the
      response criteria of the American College of Rheumatology and the European League
      Against Rheumatism, and radiographs of patients' hands and feet at months 12 and
      24 using the Van der Heijde modification of the Sharp score. Analysis was by
      intention to treat. This trial is registered with www.ClinicalTrials.gov, number
      NCT00764725. FINDINGS: Of 493 screened individuals, we enrolled 487, of whom 258
      were randomly allocated to treatment. The proportion of patients in group B who
      received a EULAR-defined good response was non-significantly greater than it was
      in group A at 18 months (49 of 128 [38%] vs 38 of 130 [29%]) and at 24 months (49
      of 128 [38%] vs 40 of 130 [31%]; p=0.204). After 24 months, radiological disease
      progression was greater in patients in group A than it was in those in group B
      (mean 7.23 [SD 12.72] vs 4.00 [10.0]; p=0.009). We recorded three serious adverse
      events: an extended generalised illness in group A, an extended febrile episode
      in group B, and a generalised illness in group B. INTERPRETATION: Additional
      biological treatment is a valid option for patients who fail initial methotrexate
      treatment. However, improved clinical outcomes after 12 months and better
      radiographical results after 24 months should be weighed against the absence of a
      convincing clinical difference at 24 months and substantially higher costs.
      Therefore, for many patients who fail initial methotrexate treatment, add-on
      treatment with disease-modifying antirheumatic drugs is an appropriate treatment
      option. FUNDING: Swedish Rheumatism Association, Stockholm County, and Schering
      Plough/Merck Sharp and Dohme.

PMID- 22464341
TI  - Personalised antiplatelet treatment: a RAPIDly moving target.

PMID- 22464342
TI  - Towards an optimum strategy in rheumatoid arthritis.

PMID- 22464343
TI  - Point-of-care genetic testing for personalisation of antiplatelet treatment
      (RAPID GENE): a prospective, randomised, proof-of-concept trial.
AB  - BACKGROUND: Prospective assessment of pharmacogenetic strategies has been limited
      by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a
      common genetic variant associated with increased rates of major adverse events in
      individuals given clopidogrel after percutaneous coronary intervention (PCI). We
      used a novel point-of-care genetic test to identify carriers of the CYP2C19*2
      allele and aimed to assess a pharmacogenetic approach to dual antiplatelet
      treatment after PCI. METHODS: Between Aug 26, 2010, and July 7, 2011, 200
      patients were enrolled into our prospective, randomised, proof-of-concept study.
      Patients undergoing PCI for acute coronary syndrome or stable angina were
      randomly assigned to rapid point-of-care genotyping or to standard treatment.
      Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele.
      Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the
      standard treatment group were given 75 mg clopidogrel daily. The primary endpoint
      was the proportion of CYP2C19*2 carriers with high on-treatment platelet
      reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of
      dual antiplatelet treatment, which is a marker associated with increased adverse
      cardiovascular events. Interventional cardiologists and data analysts were masked
      to genetic status and treatment. Patients were not masked to treatment
      allocation. All analyses were by intention to treat. This study is registered
      with ClinicalTrials.gov, NCT01184300. FINDINGS: After randomisation, 187 patients
      completed follow-up (91 rapid genotyping group, 96 standard treatment). 23
      individuals in each group carried at least one CYP2C19*2 allele. None of the 23
      carriers in the rapid genotyping group had a PRU value of more than 234 at day 7,
      compared with seven (30%) given standard treatment (p=0.0092). The point-of-care
      genetic test had a sensitivity of 100% (95% CI 92.3-100) and a specificity of
      99.3% (96.3-100). INTERPRETATION: Point-of-care genetic testing after PCI can be
      done effectively at the bedside and treatment of identified CYP2C19*2 carriers
      with prasugrel can reduce high on-treatment platelet reactivity. FUNDING: Spartan
      Biosciences.

PMID- 22464344
TI  - Discovery and structural development of small molecules that enhance transport
      activity of bile salt export pump mutant associated with progressive familial
      intrahepatic cholestasis type 2.
AB  - Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by
      hereditary mutations of bile salt export pump (BSEP), such as E297G BSEP, which
      is a folding-defective mutant that is unable to traffic beyond the endoplasmic
      reticulum (ER). 4-Phenylbutyric acid (4-PBA) enhances the cell surface expression
      and transport capacity of E297G BSEP, but has a relatively high dose (1mM or
      more) is required to show the effect. Here, we show that bile acids possibly act
      as pharmacological chaperones, promoting the proper folding and trafficking of
      E297G BSEP. We also describe the discovery and structural development of non
      steroidal compounds with potent pharmacological chaperone activity for E297G
      BSEP.

PMID- 22464345
TI  - New prognostic factors and calculators for outcome prediction in patients with
      recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and
      II clinical trials.
AB  - BACKGROUND: Prognostic models have been developed to predict survival of patients
      with newly diagnosed glioblastoma (GBM). To improve predictions, models should be
      updated with information at the recurrence. We performed a pooled analysis of
      European Organization for Research and Treatment of Cancer (EORTC) trials on
      recurrent glioblastoma to validate existing clinical prognostic factors, identify
      new markers, and derive new predictions for overall survival (OS) and progression
      free survival (PFS). METHODS: Data from 300 patients with recurrent GBM recruited
      in eight phase I or II trials conducted by the EORTC Brain Tumour Group were used
      to evaluate patient's age, sex, World Health Organisation (WHO) performance
      status (PS), presence of neurological deficits, disease history, use of steroids
      or anti-epileptics and disease characteristics to predict PFS and OS. Prognostic
      calculators were developed in patients initially treated by chemoradiation with
      temozolomide. RESULTS: Poor PS and more than one target lesion had a significant
      negative prognostic impact for both PFS and OS. Patients with large tumours
      measured by the maximum diameter of the largest lesion (?42mm) and treated with
      steroids at baseline had shorter OS. Tumours with predominant frontal location
      had better survival. Age and sex did not show independent prognostic values for
      PFS or OS. CONCLUSIONS: This analysis confirms performance status but not age as
      a major prognostic factor for PFS and OS in recurrent GBM. Patients with multiple
      and large lesions have an increased risk of death. With these data prognostic
      calculators with confidence intervals for both medians and fixed time
      probabilities of survival were derived.

PMID- 22464346
TI  - Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of
      KIT expression and mutations.
AB  - KIT aberrations predict the outcome of targeted therapies in acrolentiginous
      (ALM) and mucosal (MM) melanoma patients. KIT immunoreactivity and mutation
      status was assessed in 41 ALM and 25 MM patients. Of these, 19 ALM and 15 MM
      patients had matched primary and metastatic lesions. P-ERK was investigated in a
      subset of 9 ALM and 7 MM matched primary/metastatic pairs by
      immunohistochemistry. Heterogeneous KIT immunoreactivity was observed in both
      primary and metastatic lesions. Mutations were present in four of 41 ALM (10%)
      and five of 25 MM (20%) patients. Only vulvar mucosal samples carried KIT
      mutations in contrast to sinonasal lesions (p = 0.0109). In KIT-mutated tumours,
      the mutations were present in KIT expressing as well as KIT negative cells, as
      shown by Laser Capture Microdissection (LCM). P-ERK expression was preferentially
      found in metastases. KIT mutations predict treatment outcome with KIT inhibitors.
      Therefore, especially vulvar melanoma patients should be screened for activating
      KIT mutations.

PMID- 22464347
TI  - MC1R, SLC45A2 and TYR genetic variants involved in melanoma susceptibility in
      southern European populations: results from a meta-analysis.
AB  - BACKGROUND AND METHODS: Seven genetic biomarkers previously associated with
      melanoma were analysed in a meta-analysis conducted in three South European
      populations: five red hair colour (RHC) MC1R alleles, one SLC45A2 variant
      (p.Phe374Leu) and one thermosensitive TYR variant (p.Arg402Gln). The study
      included 1639 melanoma patients and 1342 control subjects. RESULTS: The estimated
      odds ratio (OR) associated with carrying at least one MC1R RHC variant was 2.18
      (95% confidence interval (CI): 1.86-2.55; p-value=1.02*10(-21)), with an additive
      effect for carrying two RHC variants (OR: 5.02, 95% CI: 2.88-8.94, p
      value=3.91*10(-8)). The SLC45A2 variant, p.Phe374Leu, was significantly and
      strongly protective for melanoma in the three South European populations studied,
      with an overall OR value of 0.41 (95% CI: 0.33-0.50; p-value=3.50*10(-17)). The
      association with melanoma of the TYR variant p.Arg402Gln was also statistically
      significant (OR: 1.50; 95% CI: 1.11-2.04; p-value=0.0089). Adjustment for all
      clinical potential confounders showed that melanoma risks attributable to MC1R
      and SLC45A2 variants strongly persisted (OR: 2.01 95% CI: 1.49-2.72 and OR: 0.50,
      95% CI: 0.31-0.80, respectively), while the association of TYR p.Arg402Gln was no
      longer significant. In addition, stratification of clinical melanoma risk factors
      showed that the risk of melanoma was strong in those individuals who did not have
      clinical risk factors. CONCLUSION: In conclusion, our results show without
      ambiguity that in South European populations, MC1R RHC and SCL45A2 p.Phe374Leu
      variants are strong melanoma risk predictors, notably in those individuals who
      would not be identified as high risk based on their phenotypes or exposures
      alone. The use of these biomarkers in clinical practice could be promising and
      warrants further discussion.

PMID- 22464348
TI  - Lung cancer in never smokers--a review.
AB  - An estimated 10-25% of lung cancers worldwide occur in never smokers, i.e.
      individuals having smoked less than 100 cigarettes in their lifetime. Lung cancer
      in never smokers (LCINS) is more frequent in women, although large geographic
      variations are found. Histologically, adenocarcinomas predominate. The mere
      existence of LCINS suggests that risk factors other than smoking must be present.
      Exposure to environmental tobacco smoke (particularly in women) and exposure to
      workplace carcinogens (particularly in men) are the two most important
      alternative risk factors. However, a history of either is absent in more than a
      third of LCINS. The large proportion of women in LCINS suggest a hormonal element
      that may interact with other identified factors such as hereditary risks, a
      history of respiratory infections or disease, exposure to air pollution, cooking
      and heating fumes, or exposure to ionising radiation. The study of genomic
      polymorphisms finds constitutive DNA variations across subjects according to
      their smoking status, particularly in genes coding for enzymes that participate
      in the metabolism of certain carcinogens, in those coding for DNA repair enzymes,
      or in genes associated with tobacco addiction, or inflammatory processes. The
      type of molecular mutation in p53 or KRAS varies with smoking status. EGFR
      mutations are more frequent in never smokers, as are EML4-ALK fusions. The
      mutually exclusive nature of certain mutations is a strong argument in favour of
      separate genetic paths to cancer for ever smokers and never smokers. In the
      present paper we review current clinical and molecular aspects of LCINS.

PMID- 22464349
TI  - [Self-reported cases of influenza among Spanish healthcare workers during the
      2009 influenza A(H1N1) pandemic].
AB  - OBJECTIVES: To describe the prevalence of influenza-like syndrome in winter 2009
      and the factors associated with its occurrence. METHODS: A cross-sectional study
      was carried out in 18 hospitals in Spain. Volunteers completed a health
      questionnaire in which they reported the occurrence of influenza-like syndrome
      and vaccination and demographic status. RESULTS: A total of 1,289 healthcare
      workers participated. Of these, 72 (5.6%) reported influenza in their family, 195
      (15.1%) had been vaccinated against the A/California/7/2009/H1N1 virus and 75
      (5.8%, 95%CI: 4.5-7.1%) had been diagnosed with influenza like-syndrome. There
      were differences among regions. In logistic regression analysis, the following
      factors were associated with a higher prevalence of influenza-like syndrome:
      working in Madrid (OR=8.31, 95%CI: 1.05-65.39), the occurrence of cases of
      influenza in the family (OR=2.84, 95%CI: 1.41-5.73) and not having been
      vaccinated against influenza A (H1N1) (OR=2.68, 95% CI: 1.05-6.82). CONCLUSIONS:
      Differences in the prevalence of influenza-like syndrome were due to the
      occurrence of familiar cases and region. Vaccination against influenza A (H1N1)
      was associated with a lower prevalence of the disease.

PMID- 22464350
TI  - A sleigh ride through the SNO: regulation of plant immune function by protein S
      nitrosylation.
AB  - S-nitrosylation, the covalent attachment of a nitric oxide (NO) moiety to a
      protein cysteine thiol to form an S-nitrosothiol (SNO) is rapidly emerging as a
      prototypic, redox-based post-translational modification during plant immune
      function. Here we review recently identified targets for S-nitrosylation and the
      consequences of these modifications in relation to the control of plant disease
      resistance.

PMID- 22464351
TI  - A platform for dynamic simulation and control of movement based on OpenSim and
      MATLAB.
AB  - Numerical simulations play an important role in solving complex engineering
      problems and have the potential to revolutionize medical decision making and
      treatment strategies. In this paper, we combine the rapid model-based design,
      control systems and powerful numerical method strengths of MATLAB/Simulink with
      the simulation and human movement dynamics strengths of OpenSim by developing a
      new interface between the two software tools. OpenSim is integrated with Simulink
      using the MATLAB S-function mechanism, and the interface is demonstrated using
      both open-loop and closed-loop control systems. While the open-loop system uses
      MATLAB/Simulink to separately reproduce the OpenSim Forward Dynamics Tool, the
      closed-loop system adds the unique feature of feedback control to OpenSim, which
      is necessary for most human movement simulations. An arm model example was
      successfully used in both open-loop and closed-loop cases. For the open-loop
      case, the simulation reproduced results from the OpenSim Forward Dynamics Tool
      with root mean square (RMS) differences of 0.03 degrees  for the shoulder
      elevation angle and 0.06 degrees  for the elbow flexion angle. MATLAB's variable
      step-size integrator reduced the time required to generate the forward dynamic
      simulation from 7.1s (OpenSim) to 2.9s (MATLAB). For the closed-loop case, a
      proportional-integral-derivative controller was used to successfully balance a
      pole on model's hand despite random force disturbances on the pole. The new
      interface presented here not only integrates the OpenSim and MATLAB/Simulink
      software tools, but also will allow neuroscientists, physiologists,
      biomechanists, and physical therapists to adapt and generate new solutions as
      treatments for musculoskeletal conditions.

PMID- 22464352
TI  - Quality improvement in cancer symptom assessment and control: the Provincial
      Palliative Care Integration Project (PPCIP).
AB  - CONTEXT: The Provincial Palliative Care Integration Project (PPCIP) was
      implemented in Ontario, Canada, to enhance the quality of palliative care
      delivery. The PPCIP promoted collaboration and integration across service sectors
      to improve screening and assessment, palliative care processes, as well as
      clinician practice and outcomes for cancer patients. OBJECTIVES: The project
      involved 1) implementation of the Edmonton Symptom Assessment System (ESAS) for
      symptom screening, 2) use of "rapid-cycle change" quality improvement processes
      to improve screening and symptom management, and 3) improvements in integration
      and access to palliative care services. METHODS: Symptom scores were collected
      and made accessible to the care team through a web-based tool and kiosk
      technology, which helped patients enter their ESAS scores at each visit to the
      regional cancer center or at home with their nurse. Symptom response data were
      gathered through clinical chart audits. RESULTS: Within one year of
      implementation, regional cancer centers saw improvements in symptom screening
      (54% of lung cancer patients), symptom control (69% of patients with pain scores
      and 31% of patients with dyspnea scores seven or more were reduced to six or less
      within 72 hours), and functional assessment (23% of all patients and 64% of
      palliative care clinic patients). ESAS screening rates reached 29%, and
      functional assessment reached 26% of targeted home care patients. CONCLUSION: The
      PPCIP demonstrated that significant strides in symptom screening and response can
      be achieved within a year using rapid-cycle change and collaborative approaches.
      It showed that both short- and long-term improvement require ongoing facilitation
      to embed the changes in system design and change the culture of clinical
      practice.

PMID- 22464353
TI  - Talking about end-of-life preferences with advanced cancer patients: factors
      influencing feasibility.
AB  - CONTEXT: The End-of-Life Preferences Interview (ELPI) was developed with the
      purpose of supporting physicians in communicating with advanced cancer patients.
      OBJECTIVES: This study aimed to evaluate ELPI feasibility and compare home
      care/hospice (HC-H) vs. outpatient (OU) care settings. METHODS: Twenty-eight
      physicians were trained in the use of the ELPI and were asked to apply the new
      instrument in their daily clinical practice for two months. ELPI feasibility was
      evaluated through three indices: the percentage of eligible patients, the
      percentage of patients to whom the ELPI was proposed, and the percentage of
      completed interviews. RESULTS: The 23 physicians participating in the data
      collection screened 633 patients, and 156 of them (25%, 95% confidence interval
      21%-28%) were judged to be eligible. Eligibility in HC-H was lower than that in
      the OU setting (18% vs. 46%; P<0.0001), whereas the differences were reduced when
      looking at patients to whom the ELPI was proposed (12% vs. 20%; P=0.017) and who
      completed the ELPI (8% vs. 18%; P<0.001). The percentage of eligible patients
      refusing the interview was very low in the entire sample (1.9%). CONCLUSION:
      Results indicate that discussing end-of-life preferences in an earlier disease
      phase, such as in the OU setting, could be preferable but that its accomplishment
      in this setting may be more difficult, mainly as a result of organizational
      reasons. This observation could indicate that the system is not yet ready to
      offer patients such an opportunity and although communication on these sensitive
      issues cannot be reduced to a procedure, the ELPI can become a useful tool to
      help physicians in accomplishing this difficult task.

PMID- 22464354
TI  - To stent or not to stent: an evidence-based approach to palliative procedures at
      the end of life.
AB  - Patients near the end of life often undergo invasive procedures, such as biliary
      stenting for obstructive jaundice, with the intent of relieving symptoms. We
      describe a case in which the medical team and a patient and family are
      considering a second palliative biliary stent despite the patient's limited life
      expectancy. We review available evidence to inform the decision, focusing on the
      specific question of whether the benefits of palliative biliary stents in
      patients with advanced cancer outweigh the risks. We then apply the evidence to
      the issue of how the primary and/or palliative care team and the interventionist
      communicate with patients and their families about the risks and benefits of
      palliative procedures. Review of the evidence found several prospective case
      series without control groups that measured patient-centered outcomes. Studies
      had high attrition rates, results for improvements in symptoms and quality of
      life were mixed, and rates of complications and short-term mortality were high.
      In conclusion, the limited evidence does not support that the benefits of
      palliative biliary stents in this population outweigh the risks. We propose that
      primary care teams consider and discuss the larger picture of the goals of care
      with patients and families when considering offering these procedures, as well as
      benefits and potential harms, and consider involving palliative care services
      early, before consultation with an interventionist.

PMID- 22464355
TI  - Preemptive use of palliative sedation and amyotrophic lateral sclerosis.
AB  - Patients in the advanced stages of amyotrophic lateral sclerosis often are faced
      with the dilemma of whether to use or continue to use mechanical ventilation.
      Patients who elect to terminate ventilatory support may be subject to significant
      and even extreme respiratory symptoms. Severe dyspnea and other symptoms are
      sometimes treated with palliative sedation, which is generally recommended as a
      last resort approach to refractory symptoms. However, the preemptive use of
      palliative sedation is sometimes appropriate. The preemptive use of palliative
      sedation is examined through a case-based analysis of a patient with advanced
      amyotrophic lateral sclerosis.

PMID- 22464356
TI  - PC-FACS.
AB  - PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care), an
      electronic publication of the American Academy of Hospice and Palliative
      Medicine, provides palliative care clinicians with concise summaries of the most
      important findings from more than 50 medical and scientific journals. Each month,
      structured summaries and insightful commentaries on 6-10 articles help palliative
      care clinicians stay on top of the research that is critical to contemporary
      practice. PC-FACS is free to AAHPM members. Following are excerpts from recent
      issues, and comments from readers are welcomed at resources@aahpm.org.

PMID- 22464357
TI  - Ozone therapy in the management of enterocutaneous fistulas resulting from
      postsurgery abdominal/pelvic mesh placement.

PMID- 22464358
TI  - Palliative home care for cancer patients in estonia.

PMID- 22464359
TI  - Use of methadone as a coanalgesic: response to McKenna and Nicholson.

PMID- 22464360
TI  - Sucrose during single painful procedures--no longer a state of equipoise.

PMID- 22464362
TI  - Suffering and the theory of relativity.

PMID- 22464363
TI  - Predictive model accuracy in estimating last Delta9-tetrahydrocannabinol (THC)
      intake from plasma and whole blood cannabinoid concentrations in chronic, daily
      cannabis smokers administered subchronic oral THC.
AB  - BACKGROUND: Determining time since last cannabis/Delta9-tetrahydrocannabinol
      (THC) exposure is important in clinical, workplace, and forensic settings.
      Mathematical models calculating time of last exposure from whole blood
      concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P)
      ratio. No studies previously evaluated predictive models utilizing empirically
      derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic
      THC dosing. METHODS: Ten male chronic, daily cannabis smokers received escalating
      around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were
      quantified in whole blood and plasma by two-dimensional gas chromatography-mass
      spectrometry. RESULTS: Maximum whole blood THC occurred 3.0 h after the first
      oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P
      ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy
      THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios
      accurately estimated last cannabis exposure in 96% and 100% of specimens
      collected within 1-5h after a single oral THC dose and throughout multiple
      dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h
      after the last THC dose, respectively. CONCLUSIONS: Predictive models estimating
      time since last cannabis intake from whole blood and plasma cannabinoid
      concentrations were inaccurate during abstinence, but highly accurate during
      active THC dosing. THC redistribution from large cannabinoid body stores and high
      circulating THCCOOH concentrations create different pharmacokinetic profiles than
      those in less than daily cannabis smokers that were used to derive the models.
      Thus, the models do not accurately predict time of last THC intake in individuals
      consuming THC daily.

PMID- 22464364
TI  - Sleep apnea and risk of retinal vein occlusion: a nationwide population-based
      study of Taiwanese.
AB  - PURPOSE: To explore the relationship of sleep apnea and the subsequent
      development of retinal vein occlusion (RVO). DESIGN: A retrospective
      nonrandomized, matched-control cohort study using the Taiwan National Health
      Insurance Research Database. METHODS: From 1997 through 2007, we identified newly
      diagnosed sleep apnea cases in the database. A control group without sleep apnea,
      matched for age, gender, and comorbidities, was selected for comparison. The 2
      cohorts were followed up, and the occurrence of RVO was observed. RESULTS: Of the
      35 634 sampled patients (5965 sleep apnea patients vs 29 669 controls), 52
      (0.15%) experienced RVO during a mean follow-up period of 3.72 years, including
      13 (0.22%, all branch RVO) from the sleep apnea cohort and 39 (0.13%, 39 branch
      RVO and 10 central RVO) from the control group. Kaplan-Meier analysis revealed
      the tendency of sleep apnea patients toward RVO development (P = .048, log-rank
      test). Patients with sleep apnea experienced a 1.94-fold increase (95% confidence
      interval, 1.03 to 3.65; P = .041) in incident RVO, which was independent of age,
      gender, and comorbidities. CONCLUSIONS: Sleep apnea may be an independent risk
      factor for RVO.

PMID- 22464365
TI  - Second-generation trabecular meshwork bypass stent (iStent inject) increases
      outflow facility in cultured human anterior segments.
AB  - PURPOSE: To determine whether a second-generation trabecular meshwork (TM) bypass
      stent (iStent inject) influences outflow facility in cultured human anterior
      segments. DESIGN: Prospective laboratory investigation using normal human donor
      eyes. METHODS: Human anterior segments (n = 7) were placed in perfusion organ
      culture. One or 2 iStent inject stents were inserted into the TM within the nasal
      and/or superior quadrants using a specially designed injector. Anterior segments
      were returned to culture and perfused for an additional 24 hours. Morphology of
      the TM and Schlemm canal (SC) was assessed by scanning electron microscopy (SEM)
      and 3-dimensional micro-computed tomography (3D micro-CT). RESULTS: Insertion of
      1 iStent inject into the nasal or superior quadrant of the TM increased outflow
      facility from 0.16 +/- 0.05 MUL/min/mm Hg to 0.38 +/- 0.23 MUL/min/mm Hg (P <
      .03, n = 7), with concurrent pressure reduction from 16.7 +/- 5.4 mm Hg to 8.6 +/
      4.4 mm Hg. Addition of a second iStent inject further increased outflow facility
      to 0.78 +/- 0.66 MUL/min/mm Hg (n = 2). SEM showed the iStent inject flange
      compressed against the uveal region of the TM, the thorax securely inserted
      within the TM, and the head located in the lumen of SC. Dilation of SC was noted
      around the iStent inject head and SC cell disruption was observed at the iStent
      inject insertion site. 3D micro-CT confirmed iStent inject placement. CONCLUSION:
      iStent inject, a second-generation bypass stent, increased outflow facility in
      human anterior segment culture. The iStent inject is a promising new device to
      lower intraocular pressure via TM bypass.

PMID- 22464366
TI  - Progression of retinal pigment epithelial atrophy in stargardt disease.
AB  - PURPOSE: To evaluate retinal pigment epithelial (RPE) atrophy in patients with
      Stargardt disease using autofluorescence imaging (AF). DESIGN: Retrospective
      observational case series. METHODS: Demographics, best-corrected visual acuity
      (BCVA), AF images, and electrophysiology responses (group 1, macular dysfunction;
      group 2, macula + cone dysfunction; group 3, macula + cone-rod dysfunction) were
      evaluated at presentation and follow-up in a group of 12 patients (24 eyes) with
      Stargardt disease. The existence, development, and rate of enlargement of areas
      of RPE atrophy over time were evaluated using AF imaging. A linear regression
      model was used to investigate the effects of AF and electrophysiology on rate of
      atrophy enlargement and BCVA, adjusting for age of onset and duration of disease.
      RESULTS: Eight male and 4 female patients (median age 42 years; range 24-69
      years) were followed for a median of 41.5 months (range 13-66 months). All 12
      patients had reduced AF compatible with RPE atrophy at presentation and in all
      patients the atrophy enlarged during follow-up. The mean rate of atrophy
      enlargement for all patients was 1.58 mm(2)/y (SD 1.25 mm(2)/y; range 0.13-5.27
      mm(2)/y). Only the pattern of functional loss present as detected by
      electrophysiology was statistically significantly associated with the rate of
      atrophy enlargement when correcting for other variables (P < .001), with patients
      in group 3 (macula + cone-rod dysfunction) having the fastest rate of atrophy
      enlargement (1.97 mm(2)/y, SD 0.70 mm(2)/y) (group 1 [macula] 1.09 mm(2)/y, SD
      0.53 mm(2)/y; group 2 [macula + cone] 1.89 mm(2)/y, SD 2.27 mm(2)/y). CONCLUSION:
      Variable rates of atrophy enlargement were observed in patients with Stargardt
      disease. The pattern of functional loss detected on electrophysiology was
      strongly associated with the rate of atrophy enlargement over time, thus serving
      as the best prognostic indicator for patients with this inherited retinal
      disease.

PMID- 22464368
TI  - Comparison of through-focus image sharpness across five presbyopia-correcting
      intraocular lenses.
AB  - PURPOSE: To assess through-focus polychromatic image sharpness of 5 FDA-approved
      presbyopia-correcting intraocular lenses (IOLs) through a range of object
      vergences and pupil diameters using an image sharpness algorithm. DESIGN:
      Laboratory investigation. METHODS: A 1951 USAF resolution target was imaged
      through Crystalens AO (AO), Crystalens HD (HD), aspheric ReSTOR +4 (R4), aspheric
      ReSTOR +3 (R3), and Tecnis Multifocal Acrylic (TMF) IOL in a model eye and
      captured digitally for each combination of pupil diameter and object vergence.
      The sharpness of each digital image was objectively scored using a 2-dimensional
      gradient function. RESULTS: AO had the best distance image sharpness for all
      pupil diameters and was superior to the HD. With a 5-mm pupil, the R4 distance
      image sharpness was similar to the HD and at 6 mm the TMF was superior to the HD,
      R3, and R4. The R3 moved the near focal point farther from the patient compared
      to the R4, but did not improve image sharpness at intermediate distances and
      showed worse distance and near image sharpness. Consistent with apodization, the
      ReSTOR IOLs displayed better distance and poorer near image sharpness as pupil
      diameter increased. TMF showed consistent distance and near image sharpness
      across pupil diameters and the best near image sharpness for all pupil diameters.
      CONCLUSIONS: Differing IOL design strategies to increase depth of field are
      associated with quantifiable differences in image sharpness at varying vergences
      and pupil sizes. Objective comparison of the imaging properties of specific
      presbyopia-correcting IOLs in relation to patient's pupil sizes can be useful in
      selecting the most appropriate IOL for each patient.

PMID- 22464369
TI  - End-of-life care: the neglected core business of medicine.

PMID- 22464367
TI  - Immunologic and genetic markers in patients with idiopathic ocular inflammation
      and a family history of inflammatory bowel disease.
AB  - PURPOSE: To evaluate the prevalence of immunologic and genetic markers in
      patients with idiopathic ocular inflammation and a family history of inflammatory
      bowel disease. DESIGN: Matched case-control study. METHODS: Patients with a
      diagnosis of idiopathic ocular inflammation and family history of inflammatory
      bowel disease who did not have inflammatory bowel disease themselves were
      identified and matched to control patients with idiopathic ocular inflammation.
      Serum was evaluated for immunologic markers using Prometheus IBD Serology 7.
      Genomic DNA was analyzed for single nucleotide polymorphisms (SNP) of the NOD2
      gene associated with Crohn disease. RESULTS: Fifteen patients with idiopathic
      ocular inflammation and family history of inflammatory bowel disease were matched
      to 15 control patients based on age, sex, and race. Eight of 15 patients (53%)
      with a family history of inflammatory bowel disease had elevated p-ANCA antibody
      levels compared to 3 of 15 controls (20%) (1-sided P = .04) with a matched
      analysis odds ratio of 6.0 (1-sided P = .06). Four of 15 patients (27%) with
      family history of inflammatory bowel disease tested positive for immunologic
      markers predicting ulcerative colitis, while no control patients tested positive
      (1-sided P = .06). Carrier rates of NOD2 SNPs did not differ significantly
      between the test and control groups. CONCLUSIONS: One-quarter of patients with
      idiopathic ocular inflammation and a family history of inflammatory bowel disease
      had immunologic markers predicting bowel disease, and one-half had elevated p
      ANCA levels. Prometheus IBD Serology 7 may be useful in the evaluation of
      selected patients with unexplained uveitis.

PMID- 22464370
TI  - The UK takes action on alcohol.

PMID- 22464371
TI  - Tobacco killing in low-income and middle-income countries.

PMID- 22464372
TI  - Disparities in interventions for child and maternal mortality.

PMID- 22464375
TI  - Donna McKay: taking a long lens on human rights.

PMID- 22464376
TI  - Progress towards Millennium Development Goal 4.

PMID- 22464377
TI  - Progress towards Millennium Development Goal 4.

PMID- 22464379
TI  - Failure to disclose a conflict of interest in a World Report.

PMID- 22464382
TI  - Ocrelizumab in multiple sclerosis: risks and benefits.

PMID- 22464384
TI  - Interventional cardiology and cardiac surgery in Cambodia.

PMID- 22464385
TI  - Rising maternal deaths in London, UK.

PMID- 22464386
TI  - Equity in maternal, newborn, and child health interventions in Countdown to 2015:
      a retrospective review of survey data from 54 countries.
AB  - BACKGROUND: Countdown to 2015 tracks progress towards achievement of Millennium
      Development Goals (MDGs) 4 and 5, with particular emphasis on within-country
      inequalities. We assessed how inequalities in maternal, newborn, and child health
      interventions vary by intervention and country. METHODS: We reanalysed data for
      12 maternal, newborn, and child health interventions from national surveys done
      in 54 Countdown countries between Jan 1, 2000, and Dec 31, 2008. We calculated
      coverage indicators for interventions according to standard definitions, and
      stratified them by wealth quintiles on the basis of asset indices. We assessed
      inequalities with two summary indices for absolute inequality and two for
      relative inequality. FINDINGS: Skilled birth attendant coverage was the least
      equitable intervention, according to all four summary indices, followed by four
      or more antenatal care visits. The most equitable intervention was early
      initation of breastfeeding. Chad, Nigeria, Somalia, Ethiopia, Laos, and Niger
      were the most inequitable countries for the interventions examined, followed by
      Madagascar, Pakistan, and India. The most equitable countries were Uzbekistan and
      Kyrgyzstan. Community-based interventions were more equally distributed than
      those delivered in health facilities. For all interventions, variability in
      coverage between countries was larger for the poorest than for the richest
      individuals. INTERPRETATION: We noted substantial variations in coverage levels
      between interventions and countries. The most inequitable interventions should
      receive attention to ensure that all social groups are reached. Interventions
      delivered in health facilities need specific strategies to enable the countries'
      poorest individuals to be reached. The most inequitable countries need additional
      efforts to reduce the gap between the poorest individuals and those who are more
      affluent. FUNDING: Bill & Melinda Gates Foundation, Norad, The World Bank.

PMID- 22464387
TI  - Does one plus one always equal two?

PMID- 22464388
TI  - Antibiotic treatment for uncomplicated acute appendicitis.

PMID- 22464390
TI  - Council of the European Union conclusions on chronic respiratory diseases in
      children.

PMID- 22464391
TI  - Elimination of cholera transmission.

PMID- 22464392
TI  - Propofol attenuates hepatic ischemia/reperfusion injury in an in vivo rabbit
      model.
AB  - BACKGROUND: Propofol has been demonstrated to improve hepatic perfusion in a
      rabbit model; however, the effects of propofol on hepatic ischemia/reperfusion
      injury are unknown. The aim of the present study was to determine whether
      propofol has a hepatoprotective effect using an in vivo ischemia/reperfusion
      model in rabbits. METHODS: A total of 48 rabbits were randomly assigned to two
      groups: a propofol group (0.6 mg . kg(-1) . min(-1)) or a control group (10%
      intralipid, 0.6 mg . kg(-1) . min(-1)). Each group was then further divided into
      three subgroups of 8 rabbits according to the duration (10, 30, and 60 min) of
      propofol infusion before an ischemic episode was induced by cross-clamping the
      left hepatic artery and hepatic portal vein. Hepatic ischemia was maintained for
      30 min, and the rabbits were monitored for 60 min after reperfusion. Liver enzyme
      leakage and histopathologic examination were used to evaluate the extent of
      hepatic ischemia/reperfusion injury. RESULTS: The serum enzyme levels were the
      same in all groups before the ischemic episode. After the induction of
      ischemia/reperfusion, the liver enzymes were significantly increased in all
      rabbits compared with baseline values (P < 0.05). Propofol significantly
      decreased the leakage of liver enzymes and markedly reduced lesions in histologic
      examination of the liver compared with the control group (P < 0.05). However, no
      significant difference was found in serum enzyme levels among the three subgroups
      in the propofol group. CONCLUSIONS: Propofol reduced hepatic ischemia/reperfusion
      injury in an in vivo rabbit model; however, the duration of propofol infusion
      before the ischemic insult did not influence its hepatoprotective effects or the
      extent of hepatic injury.

PMID- 22464393
TI  - The potential role and mechanisms of distilled water-induced hypotonic shock on
      malignant cells.

PMID- 22464394
TI  - Hydrogen sulfide decreases reactive oxygen in a model of lung transplantation.
AB  - BACKGROUND: Ischemia-reperfusion injury is a common complication after lung
      transplantation. Ischemia-reperfusion injury is thought to be mediated by
      reactive oxygen species (ROS). Hydrogen sulfide (H(2)S) is a novel agent that has
      been previously shown to scavenge ROS and slow metabolism. We evaluated the
      effect of infused H(2)S on the presence of ROS after reperfusion in an ex vivo
      model of lung transplantation. METHODS: Heart-Lung blocks were recovered from New
      Zealand white rabbits (n = 12) and cold stored in Perfadex solution for 18 h.
      After storage, the heart-lung blocks were reperfused ex vivo with donor rabbit
      blood. In the treatment group (n = 7), a bolus of sodium H(2)S was added at the
      beginning of reperfusion (100 MUg/kg) and continuously infused throughout the 2-h
      experiment (1 mg/kg/h). The vehicle group (n = 5) received an equivalent volume
      of saline. Serial airway and pulmonary artery pressures and arterial and venous
      blood gases were measured. RESULTS: Oxygenation and pulmonary artery pressures
      were similar between the 2 groups. However, treatment with H(2)S resulted in a
      dramatic reduction in the presence of ROS after 2 h of reperfusion (4,851 +/-
      2,139 versus 235 +/- 462 related fluorescence units/mg protein; P = 0.003). A
      trend was seen toward increased levels of cyclic guanosine monophosphate in the
      H(2)S-treated group (3.08 +/- 1.69 versus 1.73 +/- 1.41 fmol/mg tissue; P = .23).
      CONCLUSIONS: After prolonged ischemia, infusion of H(2)S during reperfusion was
      associated with a significant decrease in the presence of ROS, a suspected
      mediator of ischemia-reperfusion injury. To our knowledge, the present study
      represents the first reported therapeutic use of H(2)S in an experimental model
      of lung transplantation.

PMID- 22464395
TI  - Biologic sealants: the next great thing in gastrointestinal surgery?

PMID- 22464397
TI  - Adverse selection and moral hazard in the provision of clinical trial ancillary
      care.
AB  - As more and more clinical trials are conducted in developing countries, concerns
      arise about non-trial medical care available to study participants. Recent work
      argues for ancillary care - medical care not part of the clinical trial per se -
      to be formally incorporated into these studies. Although the provision of
      ancillary care is often justified on ethical grounds, a number of crucial
      implementation issues remain unresolved, including its scope, duration and
      financing. Drawing on lessons from health insurance benefit design, we highlight
      two overlooked challenges for ancillary care adoption - adverse selection and
      moral hazard - and offer recommendations that could attenuate their consequences.
      Specifically, adverse selection and moral hazard could be reduced by offering a
      choice between ancillary medical care and monetary compensation or rewarding low
      ancillary care utilization. Alternatively, researchers' financial risk due to
      ancillary care could be shifted to a third-party insurer. Recognizing
      participants' behavioral responses to prospective offers of ancillary medical
      care would allow funders and research teams to forecast the demand for ancillary
      care more accurately and to prepare for its provision more adequately.

PMID- 22464396
TI  - Inhibitory kappa-B kinase-beta inhibition prevents adaptive left ventricular
      hypertrophy.
AB  - BACKGROUND: Most cardiovascular studies have implicated the central transcription
      factor nuclear factor kappa-B (NF-kappaB) as contributing to the detrimental
      effects of cardiac injury. This ostensibly negative view of NF-kappaB competes
      with its important role in the normal host inflammatory and immune response.
      Pressure overload, left ventricular hypertrophy (LVH), and heart failure
      represent a spectrum of disease that has both adaptive and maladaptive
      components. In contrast to its known effects related to myocardial ischemia
      reperfusion, we hypothesized that NF-kappaB is necessary for the compensatory
      phase of cardiac remodeling. METHODS: C57BL6 mice underwent minimally invasive
      transverse aortic constriction with or without inhibition of the proximal NF
      kappaB kinase, inhibitory kappa-B kinase-beta. Isolated cardiomyocytes were
      cultured. Transthoracic echocardiography was performed on all mice. RESULTS:
      Inhibitory kappa-B kinase-beta inhibition successfully decreased cardiomyocyte
      expression of phosphorylated p65 NF-kappaB and decreased expression of
      hypertrophic markers with stimulation in vitro. Three weeks after transverse
      aortic constriction, the mice treated with inhibitory kappa-B kinase-beta
      inhibition more aggressively developed LVH, as measured by heart weight/body
      weight ratio, left ventricular mass, and wall thickness. These mice also
      demonstrated a functional decline, as measured by decreased fractional shortening
      and ejection fraction. These findings were associated with decreased protein
      expression of p65 NF-kappaB. CONCLUSIONS: Although short-term pressure-overload
      results in compensatory LVH with normal cardiac function, NF-kappaB inhibition
      resulted in increased LVH that was associated with functional deterioration.
      These observations suggest that NF-kappaB is an important part of the adaptive
      phase of LVH, and its inhibition detrimentally affects cardiac remodeling.

PMID- 22464398
TI  - Tracking multiple pathways of waste from a northern bluefin tuna farm in a marine
      coastal area.
AB  - Aquaculture of bluefin tuna in Mediterranean coastal waters has generated growing
      concern about the negative environmental effects. In the present isotopic study
      we examined the dispersal and fate of organic matter derived from a Mediterranean
      tuna farm in the surrounding environment. An overall enrichment in the heavy
      nitrogen isotope was found in the feed and in farmed tunas, indicating the input
      of isotopically traceable organic matter in the system. Waste was clearly
      traceable in the water column up to 1000 m from the cages, while only slight
      accumulation occurred in the sediment just below the cages. Waste was
      isotopically shown also to contribute to the diet of demersal and benthopelagic
      wild fish collected around the cages. As a result, waste undertook multiple
      pathways. In the water column its was diluted and dispersed due to hydrodynamism,
      which prevented great accumulation of aquaculture-derived organic matter in
      sediments. In addition, biological constraints such as benthopelagic and demersal
      fish further prevented organic matter accumulation through the benthic trophic
      route.

PMID- 22464399
TI  - Analysis of humoral immune responses to LM1 ganglioside in guinea pigs.
AB  - Guillain-Barre syndrome (GBS) is an autoimmune-mediated disease triggered by a
      preceding infection. A substantial body of evidence implicates antibodies to
      various gangliosides in subtypes of GBS. A significant proportion of patients
      with acute demyelinating subset of GBS have IgG antibodies against peripheral
      nervous system myelin specific neolactogangliosides such as LM1 and Hex-LM1.
      Although anti-neolactoganglioside antibodies in GBS were described more than two
      decades ago, their pathogenic role in neuropathy remains unknown due to the lack
      of suitable experimental models. In this study, we immunized ten guinea pigs with
      purified LM1 ganglioside mixed with keyhole limpet hemocyanin (KLH) and
      emulsified in complete Freund's adjuvant (CFA). Control guinea pigs were injected
      with KLH emulsified in CFA only. The animals were bled every four week intervals.
      The animals were boosted 3 times every four weeks. Experiments were terminated
      four months after initial immunization. Nine of 10 guinea pigs immunized with LM1
      exhibited antibody responses to LM1. Anti-LM1 IgG titers in nine guinea pigs
      ranged from 1:400 to 1:12,800 at 16-weeks after initial immunization. Anti-LM1
      antibodies were predominantly of IgG2 subclass. One guinea pig with the highest
      levels of IgG antibodies exhibited mild signs of neuropathy. There was no
      evidence of demyelination or inflammation in the sciatic nerves of LM1-immunized
      guinea pigs. Anti-LM1 antibodies bound to rat sciatic nerve myelin and to
      isolated rat Schwann cells. In summary, our findings suggest that relatively high
      levels of anti-LM1 IgG antibodies can be induced in guinea pigs and that LM1 is
      localized in peripheral nerve myelin and in Schwann cells. Further studies are
      needed to determine the pathogenic potential of anti-neolactoganglioside
      antibodies in neuropathy.

PMID- 22464400
TI  - Effect of weight loss on inflammatory biomarkers in obese dogs.
AB  - The objective of this study was to evaluate the effects of weight loss on
      selected serum inflammatory biomarkers in obese dogs. An experimentally induced
      bodyweight reduction of approximately 2.5%/week was accompanied by significant
      decreases in metabolic markers of obesity (lipidic profile, fructosamine, and
      insulin-like growth factor-1). The concentrations of acute phase proteins and of
      selected cytokines remained within reference ranges in obese dogs during weight
      loss, suggesting that significant inflammation was not a major component of this
      experimental model. However, adiponectin concentrations increased following the
      period of weight loss suggesting reduced susceptibility of these animals to
      obesity-related inflammation.

PMID- 22464401
TI  - Finite element analysis in 3-D models of equine cheek teeth.
AB  - Periodontal diseases occur frequently in equine dentistry and excessive strain in
      biological tissues is assumed to be a predisposing factor in their development.
      Finite element (FE) analysis enables strains and stresses occurring in the
      periodontium to be calculated and is a useful tool for testing this hypothesis.
      The current study aimed to establish reliable 3-D models from equine maxillary
      and mandibular cheek teeth for use in FE simulations, with particular attention
      to the detailed construction of the periodontal ligament (PDL). Age-related
      morphological aspects of the teeth and the periodontium were also considered by
      constructing different models for three defined age groups. Finally, the
      biomechanical behaviour of the equine PDL was examined during experimental tooth
      intrusion (i.e. axial displacement of the tooth into its alveolar socket). The
      results showed an increase in intrusion with increasing age due to age-related
      changes in the periodontal elastic properties. The general stress level in PDL
      and surrounding bone also increased with age. Reliable FE models were established
      to calculate aetiologically relevant biomechanical effects occurring in the
      equine periodontium.

PMID- 22464402
TI  - Solid-state nuclear magnetic resonance structural studies of proteins using
      paramagnetic probes.
AB  - Determination of three-dimensional structures of biological macromolecules by
      magic-angle spinning (MAS) solid-state NMR spectroscopy is hindered by the
      paucity of nuclear dipolar coupling-based restraints corresponding to distances
      exceeding 5 A. Recent MAS NMR studies of uniformly (13)C,(15)N-enriched proteins
      containing paramagnetic centers have demonstrated the measurements of site
      specific nuclear pseudocontact shifts and spin relaxation enhancements, which
      report on electron-nucleus distances up to ~20 A. These studies pave the way for
      the application of such long-distance paramagnetic restraints to protein
      structure elucidation and analysis of protein-protein and protein-ligand
      interactions in the solid phase. Paramagnetic species also facilitate the rapid
      acquisition of high resolution and sensitivity multidimensional solid-state NMR
      spectra of biomacromolecules using condensed data collection schemes, and
      characterization of solvent-accessible surfaces of peptides and proteins. In this
      review we discuss some of the latest applications of magic-angle spinning NMR
      spectroscopy in conjunction with paramagnetic probes to the structural studies of
      proteins in the solid state.

PMID- 22464403
TI  - The changes of calretinin immunoreactivity in paraquat-induced nephrotoxic rats.
AB  - Calcium-binding proteins are present in the kidneys: calbindin D-28k in the
      distal tubules and calretinin in the proximal tubules. Since paraquat causes
      degeneration in the brush border-bearing proximal tubule cells in rat kidneys, we
      investigated the changes of calretinin immunoreactivity in the proximal tubule
      cells of paraquat-induced nephrotoxicity in experimental male Sprague-Dawley rats
      following chitosan oligosaccharide pretreatment to investigate its protective
      properties. Paraquat (60 mg/kg) was administered intraperitoneally with or
      without chitosan oligosaccharide (500 mg/kg, p.o.) pretreatment. The changes on
      calretinin were compared with those of calbindin D-28k by immunohistochemistry
      and Western Blot analysis. Calretinin was immunolocalized on the apical surface
      of proximal tubule cells in the deeper cortex of normal kidney, and disappeared
      after paraquat administration with minor changes of calbindin D-28k
      immunoreactivity in the distal tubules and collecting ducts. Chitosan
      oligosaccharide pretreatment caused increased expression of calretinin and
      calbindin D-28k before paraquat injection and helped preserve proximal tubules
      after paraquat treatment. However, Western blot analysis on calretinin and
      calbindin D-28k could not explain the degeneration of the proximal tubule cells
      in paraquat-induced nephrotoxicity. These findings suggested that calretinin is a
      possible and more useful histopathological marker for proximal tubule cells in
      paraquat-induced nephrotoxic rats.

PMID- 22464404
TI  - [Tobacco: the taxation is also a tool of public health].

PMID- 22464405
TI  - Clinical diagnosis of completeness of medical abortion by nurses: a reliability
      study in Mozambique.
AB  - BACKGROUND: The provision of medical abortion continues to rely on routine use of
      ultrasound to confirm expulsion of pregnancy. However, the absence of ultrasound
      in most of the health facilities in developing countries and the additional
      training required to enable providers to use ultrasound is often prohibitive. The
      purpose of this study was to compare clinical history and physical examination
      with ultrasound in confirming completion of abortion. STUDY DESIGN: A total of
      718 women consented for medical abortion with misoprostol and were assessed for
      pregnancy expulsion by nurses and gynecologists. Nurses used history and physical
      examination while gynecologists used ultrasound to establish their diagnoses.
      RESULTS: Nurses' clinical diagnoses for complete abortion, incomplete abortion
      and ongoing pregnancy were 83% (SE 0.01), 15% (SE 0.01) and 2% (SE 0.01),
      respectively. When gynecologists used ultrasound, the diagnoses for complete
      abortion, incomplete abortion, an ongoing pregnancy were 80% (SE 0.01), 17% (SE
      0.01) and 3% (SE 0.01), respectively. Overall, nurses agreed with gynecologist
      diagnoses in 84% of cases, with a kappa coefficient of 0.49 (SE 0.06) and chance
      corrected first-order agreement (AC(1)) of 0.81 (SE 0.02). Agreement was very
      high for the diagnosis of complete abortion (AC(1) 0.89; SE 0.02), while it was
      moderate for ongoing pregnancy (AC(1) 0.58; SE 0.22) and incomplete abortion
      (AC(1) 0.45; SE 0.08). CONCLUSIONS: Clinical history and physical examination
      alone, without the use of ultrasonography, are effective for the determination of
      successful pregnancy expulsion. However, greater emphasis is required on the
      clinical identification of ongoing pregnancy during any training of providers.

PMID- 22464406
TI  - Does using tampons or menstrual cups increase early IUD expulsion rates?
AB  - BACKGROUND: Many intrauterine device (IUD) users utilize intravaginal menstrual
      cups or tampons during menses, but no studies have investigated the impact this
      practice may have on IUD expulsions. STUDY DESIGN: Retrospective chart survey.
      RESULTS: Of the 930 women having IUDs placed and reporting menstrual protection,
      10.3% (96) used menstrual cups, 74.2% (690) used tampons, and 43.2% (402) used
      pads (many women reported using more than one method). In the 743 women with
      adequate follow-up information, there was a full or partial expulsion (i.e., part
      of the IUD in the cervical canal) rate of 2.5% (27) during the first 6 weeks
      after insertion. There was no difference in the women using cups, tampons or pads
      (confidence intervals overlap). CONCLUSIONS: From this study, there is no
      evidence that women who report using menstrual cups or tampons for menstrual
      protection had higher rates of early IUD expulsion.

PMID- 22464407
TI  - The effect on use of making emergency contraception available free of charge.
AB  - BACKGROUND: Cost is a barrier to use of emergency contraception (EC). Since 2008,
      EC has been available free of charge without restriction in pharmacies throughout
      Scotland. A survey of EC use among women requesting abortion in 2010 allows
      comparison of use reported in earlier surveys, when EC was only available on
      prescription and when EC was available from the pharmacy but at a cost. STUDY
      DESIGN: A questionnaire survey about knowledge of the availability of free EC
      from pharmacies, and its use to prevent the index pregnancy, was performed among
      204 women requesting abortion in Edinburgh, Scotland. RESULTS: Seventy percent of
      204 respondents (n=143) knew that EC was available free from pharmacies; 22 (11%)
      had used it in the cycle in which conception occurred. EC use was not influenced
      by knowledge of its availability free of charge. Women from affluent areas were
      significantly more likely to have used EC to try to prevent the pregnancy than
      counterparts from less affluent areas (p=.041). CONCLUSIONS: Neither availability
      from the pharmacy nor removal of a charge for EC has increased its use among
      women having an abortion in Scotland.

PMID- 22464408
TI  - Effect of hormonal contraceptives on vitamin B12 level and the association of the
      latter with bone mineral density.
AB  - BACKGROUND: The study was conducted to estimate the effect of depot
      medroxyprogesterone acetate (DMPA) and oral contraceptives (OC) containing 20 mcg
      ethinyl estradiol on serum B12 and whether observed changes impact bone mineral
      density (BMD). STUDY DESIGN: Serum B12 and BMD at the lumbar spine and femoral
      neck were measured on 703 women using OC, DMPA or nonhormonal (NH) birth control
      at baseline and every 6 months thereafter for 3 years. RESULTS: OC and DMPA users
      experienced greater decreases in B12 than NH users (p<.001). A sharp decrease in
      B12 was observed during the first 6 months of hormonal contraceptive use (OC: 97
      pg/mL and DMPA: 64 pg/mL) in contrast to 14 pg/mL among NH users (20%, 13% and 3%
      of their baseline values, respectively). Over the following 30 months, B12 levels
      of OC users remained almost flat, while DMPA users had a further 22-unit
      decrease. Very few women demonstrated B12 deficiency. Moreover, B12 levels were
      not associated with BMD. CONCLUSION: Hormonal contraception causes B12 levels to
      decrease, but this does not appear to be clinically significant or affect BMD.

PMID- 22464409
TI  - The New York City mayoral abortion training initiative at public hospitals.
AB  - BACKGROUND: We set out to describe and understand the first-ever abortion
      training political initiative on the provision of abortion services and abortion
      residency training. STUDY DESIGN: We completed in-depth interviews with 22
      participants (response rate of 92%) who have knowledge of abortion training and
      services in the New York City (NYC) public hospital system before and/or after
      the initiative. We used grounded theory to describe the initiative's effects.
      RESULTS: Respondents identified strategies that helped achieve renovation of
      abortion facilities, updating of abortion services and protocols, and training of
      abortion providers. Respondents also identified public health impacts including
      improvement of abortion services, empowerment of abortion providers, and
      legitimization of abortion training and services. CONCLUSION: This NYC political
      initiative can be a model for other city governments to influence obstetrics and
      gynecology resident training and the provision of abortion services.

PMID- 22464410
TI  - The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or
      combined with spironolactone, on cardiovascular risk markers in women with
      polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder associated
      with metabolic dysfunction and changes in cardiovascular risk markers, and using
      oral contraceptives (OCs) may exert a further negative effect on these
      alterations in patients with PCOS. Thus, the primary objective of this study was
      to assess the effects on arterial function and structure of an OC containing
      chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined
      with spironolactone (OC+SPL), in patients with PCOS. STUDY DESIGN: This was a
      randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35
      years of age were randomized by a computer program to use OC or OC+SPL. Brachial
      artery flow-mediated vasodilation, carotid intima-media thickness and the carotid
      artery stiffness index were evaluated at baseline and after 6 and 12 months.
      Serum markers for cardiovascular disease were also analyzed. The intragroup data
      were analyzed using analysis of variance with Tukey's post hoc test. A
      multivariate linear regression model was used to analyze the intergroup data.
      RESULTS: At 12 months, the increase in mean total cholesterol levels was greater
      in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The
      increase in mean sex hormone-binding globulin levels was greater in the OC group
      than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically
      significant differences between the groups were found for any of the other
      variables. CONCLUSION: The addition of spironolactone to an OC containing
      chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk
      marker advantages in young women with PCOS.

PMID- 22464411
TI  - A qualitative study of contraceptive understanding among young adults.
AB  - BACKGROUND: This study describes contraceptive understanding, sources of
      information and consequences of contraceptive misunderstandings among urban,
      young adults. STUDY DESIGN: We used qualitative data from 16 focus groups and 53
      interviews with Puerto Rican and African American men and women aged 18-25 years
      from Philadelphia and Hartford. We categorized and compared assertions made about
      all contraceptive methods' side effects, effectiveness and use using an iterative
      process. RESULTS: Participants considered contraceptive use worthwhile but felt
      that it carried risks of problematic side effects and contraceptive failure, with
      variation among methods. Men knew most about condoms and withdrawal and trusted
      both more than women. Personal or second-hand experience was the dominant source
      of information on contraceptive understanding. Misunderstandings about
      contraception affected their relationships and risk of unintended pregnancy.
      CONCLUSION: Contraceptive understanding is a powerful determinant of
      contraceptive use and limits the options perceived by young adults to prevent
      pregnancy. Research is needed to strengthen contraceptive counseling and outreach
      in ways that better leverage peer influence.

PMID- 22464412
TI  - Antiabortion violence in the United States.
AB  - BACKGROUND: This study was conducted to determine if an association exists
      between the amount of harassment and violence directed against abortion providers
      and the restrictiveness of state laws relating to family planning. STUDY DESIGN:
      We used responses from a July 2010 survey of 357 abortion providers in 50 states
      to determine their experience of antiabortion harassment and violence. Their
      responses were grouped and analyzed in relation to a published grading of state
      laws in the United States (A, B, C, D and F) as they relate to restrictions on
      family planning services. RESULTS: Group by group comparison of respondents
      illustrates that the difference in the number of reported incidents of minor
      vandalism by group is statistically significant (A vs. C, p=.07; A vs. D, p=.017;
      A vs. F, p=.0002). Incidents of harassment follow a similar pattern. There were
      no differences noted overall for violence or major vandalism. Major violence,
      including eight murders, is a new occurrence in the last two decades.
      CONCLUSIONS: Harassment of abortion providers in the United States has an
      association with the restrictiveness of state abortion laws. In the last two
      decades, murder of abortion providers has become an unfortunate part of the
      violence.

PMID- 22464413
TI  - A Compton scattering study of refractory niobium diborides.
AB  - Isotropic Compton profile of NbB(2) using 20 Ci (137)Cs Compton spectrometer is
      compared with our theoretical profiles obtained from the density functional
      theory (DFT) within the first and the second order generalized gradient
      approximation (GGA) and the hybridization of Hartree-Fock and DFT. A good
      agreement between GGA based profiles and the experiment validates the
      applicability of second order GGA in momentum densities. Energy bands, density of
      states and real space analysis of the experimental profile show metallic
      character of NbB(2).

PMID- 22464414
TI  - Two methods provide similar signals for the need to update systematic reviews.
AB  - OBJECTIVE: Apply and compare two methods that identify signals for the need to
      update systematic reviews, using three Evidence-based Practice Center reports on
      omega-3 fatty acids as test cases. STUDY DESIGN AND SETTING: We applied the RAND
      method, which uses domain (subject matter) expert guidance, and a modified Ottawa
      method, which uses quantitative and qualitative signals. For both methods, we
      conducted focused electronic literature searches of recent studies using the key
      terms from the original reports. We assessed the agreement between the methods
      and qualitatively assessed the merits of each system. RESULTS: Agreement between
      the two methods was "substantial" or better (kappa>0.62) in three of the four
      systematic reviews. Overall agreement between the methods was "substantial"
      (kappa=0.64, 95% confidence interval [CI] 0.45-0.83). CONCLUSION: The RAND and
      modified Ottawa methods appear to provide similar signals for the possible need
      to update systematic reviews in this pilot study. Future evaluation with a
      broader range of clinical topics and eventual comparisons between signals to
      update reports and the results of full evidence review updates will be needed. We
      propose a hybrid approach combining the best features of both methods, which
      should allow efficient review and assessment of the need to update.

PMID- 22464415
TI  - Decreased and inactivated nuclear factor kappa B 1 (p50) in human degenerative
      calcified aortic valve.
AB  - BACKGROUND: Degenerative aortic valve calcification is an important factor in
      aortic stenosis and incompetence, but the pathogenesis is unclear. The purpose of
      the present study was to observe the expression of p50 in degenerative calcified
      aortic valves, which may provide a potential therapeutic target. METHODS: Fifteen
      cases of degenerative calcified aortic valve constituted the experimental group,
      and 10 aortic valves from patients who had undergone the Bentall operation
      constituted the control group. RESULTS: Immunostaining demonstrated that alpha
      smooth muscle actin was highly expressed in valvular interstitial cells in the
      experimental group and that the percentage of CD68-positive cells was
      significantly higher in degenerative calcified aortic valves. Using bone gamma
      carboxyglutamate protein as a marker of calcification showed that osteoblasts
      were significantly increased in the experimental valves. Western blot showed that
      p50 was more highly expressed and activated in the control group compared with
      the experimental group. Immunohistochemistry confirmed this finding and showed
      that p50 was principally localized to the endothelial cells of uncalcified
      valves, suggesting that it might play an important role in maintaining valve
      function. CONCLUSIONS: Inhibition of p50 activity in endothelial cells might lead
      to calcification in degenerative calcified aortic valves.

PMID- 22464416
TI  - Early detection of protozoan grazers in algal biofuel cultures.
AB  - Future micro-algal biofuels will most likely be derived from open-pond production
      systems. These are by definition open to "invasion" by grazers, which could
      devastate micro-algal mass-cultures. There is an urgent requirement for
      methodologies capable of early detection and control of grazers in dense algal
      cultures. In this study a model system employing the marine alga Nannochloropsis
      oculata was challenged by grazers including ciliates, amoebae and a heterotrophic
      dinoflagellate. A FlowCAM flow-cytometer was used to detect all grazers
      investigated (size range <20->80 MUm in length) in the presence of algae.
      Detection limits were <10 cells ml(-1) for both "large" and "small" model
      grazers, Euplotes vannus (80 * 45 MUm) and an unidentified holotrichous ciliate
      (~18 * 8 MUm) respectively. Furthermore, the system can distinguish the presence
      of ciliates in N. oculata cultures with biotechnologically relevant cell
      densities; i.e. >1.4 * 10(8) cells ml(-1) (>0.5 g l(-1) dry wt.).

PMID- 22464417
TI  - Is ammonification the rate limiting step for nitrification kinetics?
AB  - This study investigated relative magnitude of hydrolysis and ammonification by
      separate analysis of ammonia release and nitrification mechanisms. A peptone
      mixture was used as substrate in two parallel experiments seeded with nitrifying
      biomass conducted with and without nitrification inhibitor. Results were
      evaluated by means of model analysis of the ammonia and the oxygen uptake rate
      (OUR) profiles. A dual hydrolysis mechanism with maximum rate coefficients of 6.3
      and 0.5/day characterized the peptone mixture and a kinetic balance was
      established for the ammonia release mechanism with a corresponding ammonification
      rate of 0.08 m(3)/g COD day. The experiments also showed a low soluble ammonia
      nitrogen generation that was rapidly depleted, confirming the existence of
      ammonification. These rate coefficients were verified using model calibration of
      the OUR profile related to simultaneous carbon removal and nitrification. Results
      indicated that ammonification would not be rate limiting for wastewaters such as
      domestic sewage, with lower hydrolysis kinetics.

PMID- 22464418
TI  - Genetic and chemical analyzes of transformations in compost compounds during
      biodegradation of oiled bleaching earth with waste sludge.
AB  - Composting of oiled bleaching earth with waste sludge and corn straw was carried
      out to investigate the ability of microorganisms to synthesize biosurfactants
      that might decrease the surface tension of composts. Analytical results and
      changes in the surface tension suggest that biodegradation of fatty by-products
      was the consequence of emulsifying properties of higher fatty acids. The surface
      tension for isolates from all composting phases was between 37 and 43 mN m(-1).
      No substances synthesized by microorganisms that might be able to decrease the
      surface tension were detected in composts. Tensammetric, TLC and HPLC-MS results
      and changes in surface tension suggest that biodegradation of fatty by-products
      results from the emulsifying properties of higher fatty acids. A decrease in
      fatty content from 144 to 6 mg g(-1) dry matter was obtained.

PMID- 22464419
TI  - Bioconversion of volatile fatty acids into lipids by the oleaginous yeast
      Yarrowia lipolytica.
AB  - The valorization of volatile fatty acids into microbial lipids by the oleaginous
      yeast Yarrowia lipolytica was investigated. Therefore, a two-stage fed-batch
      strategy was designed: the yeast was initially grown on glucose or glycerol as
      carbon source, then sequential additions of acetic acid under nitrogen limiting
      conditions were performed after glucose or glycerol exhaustion. The typical
      values obtained with an initial 40 g/L concentration of glucose were close to 31
      g/L biomass, a lipid concentration of 12.4 g/L, which correspond to a lipid
      content of the biomass close to 40%. This cultivation strategy was also efficient
      with other volatile fatty acids (butyric and propionic acids) or with a mixture
      of these three VFAs. The lipids composition was found quite similar to that of
      vegetable oils. The study demonstrated the feasibility of simultaneous
      biovalorization of volatile fatty acids and glycerol, two cheap industrial by
      products.

PMID- 22464420
TI  - BODIPY staining, an alternative to the Nile Red fluorescence method for the
      evaluation of intracellular lipids in microalgae.
AB  - In order to develop feasible production processes for microalgal biodiesel, the
      isolation of high neutral lipid producing microalgae is crucial. Since the
      established Nile Red (NR) method for detection of intracellular lipids has been
      successful only for some microalgae, a more broadly applicable detection method
      would be desirable. Therefore, BODIPY 505/515, a lipophilic bright green
      fluorescent dye was tested for detection of intracellular lipids in Chlorella
      vulgaris, Dunaliella primolecta and Chaetoceros calcitrans. An optimum
      concentration of 0.067 MUg ml(-1) was determined for lipid staining in the
      microalgae. Compared to NR, BODIPY 505/515 was more effective in staining
      microalgae and showed resistance to photobleaching, maintaining its fluorescence
      longer than 30 min.

PMID- 22464421
TI  - Preparation of novel magnetic chitosan/graphene oxide composite as effective
      adsorbents toward methylene blue.
AB  - A novel magnetic composite bioadsorbent composed of magnetic chitosan and
      graphene oxide (MCGO) was prepared as the magnetic adsorbent toward methylene
      blue. The magnetic composite bioadsorbent was characterized by SEM, FTIR and XRD
      measurements. The effect factors including pH, contact time and temperature on
      the adsorption properties of methylene blue onto MCGO were investigated. The
      resulting shows extraordinary adsorption capacity and fast adsorption rates for
      removal of methylene blue. The kinetics are well-described by pseudo-second-order
      kinetic. The experimental data of isotherm followed the Langmuir isotherm model
      and the Freundlich model, respectively. This work shows that the MCGO could be
      utilized as an efficient, magnetically separable adsorbent for the environmental
      cleanup.

PMID- 22464422
TI  - Improved biogas production from whole stillage by co-digestion with cattle
      manure.
AB  - Whole stillage, as sole substrate or co-digested with cattle manure, was
      evaluated as substrate for biogas production in five mesophilic laboratory-scale
      biogas reactors, operating semi-continuously for 640 days. The process
      performance was monitored by chemical parameters and by quantitative analysis of
      the methanogenic and acetogenic population. With whole stillage as sole substrate
      the process showed clear signs of instability after 120 days of operation.
      However, co-digestion with manure clearly improved biogas productivity and
      process stability and indicated increased methane yield compared with theoretical
      values. The methane yield at an organic loading rate (OLR) at 2.8 g VS/(L*day)
      and a hydraulic retention time (HRT) of 45 days with a substrate mixture 85%
      whole stillage and 15% manure (based on volatile solids [VS]) was 0.31 N L
      CH(4)/gVS. Surprisingly, the abundance of the methanogenic and acetogenic
      populations remained relatively stable throughout the whole operation and was not
      influenced by process performance.

PMID- 22464423
TI  - Exploring the interplay of physicochemical properties, membrane permeability and
      giardicidal activity of some benzimidazole derivatives.
AB  - This study evaluated the relationship between the physicochemical properties,
      membrane permeability and in vitro giardicidal activity of twenty nine
      benzimidazole derivatives (1-7n). The retention time data from reverse phase high
      performance chromatography (RP-HPLC) were used to estimate aqueous solubility and
      lipophilicity of these compounds. The apparent permeability was determined using
      Caco-2 cell monolayer. The calculation of some descriptors, such as Clog P, PSA,
      was performed using ACD labs software. For benzimidazole derivatives with
      NHCOOCH(3), CH(3), NH(2), SH and SCH(3) groups at the 2-position, a quadratic
      type of regression model was obtained with giardicidal activity and aqueous
      solubility or lipophilicity. On the other hand, giardicidal activity of 2
      (trifluoromethyl)-1H-benzimidazole derivatives was influenced by lipophilicity,
      hydrogen bond donors and molecular volume but it was not determined by their
      apparent permeability in Caco-2 cell line.

PMID- 22464425
TI  - Selfish cellular networks and the evolution of complex organisms.
AB  - Human gametogenesis takes years and involves many cellular divisions,
      particularly in males. Consequently, gametogenesis provides the opportunity to
      acquire multiple de novo mutations. A significant portion of these is likely to
      impact the cellular networks linking genes, proteins, RNA and metabolites, which
      constitute the functional units of cells. A wealth of literature shows that these
      individual cellular networks are complex, robust and evolvable. To some extent,
      they are able to monitor their own performance, and display sufficient autonomy
      to be termed "selfish". Their robustness is linked to quality control mechanisms
      which are embedded in and act upon the individual networks, thereby providing a
      basis for selection during gametogenesis. These selective processes are equally
      likely to affect cellular functions that are not gamete-specific, and the
      evolution of the most complex organisms, including man, is therefore likely to
      occur via two pathways: essential housekeeping functions would be regulated and
      evolve during gametogenesis within the parents before being transmitted to their
      progeny, while classical selection would operate on other traits of the organisms
      that shape their fitness with respect to the environment.

PMID- 22464424
TI  - 2-Aminothiophenes as building blocks in heterocyclic synthesis: synthesis and
      antimicrobial evaluation of a new class of pyrido[1,2-a]thieno[3,2-e]pyrimidine,
      quinoline and pyridin-2-one derivatives.
AB  - Multisubstituted 2-aminothiophenes 1a-c can be readily cyanoacylated via reaction
      with cyanoacetic acid in presence of acetic anhydride under a microwave
      irradiation to form the corresponding cyanoacetamides 2a-c, which condensed with
      DMF-DMA to form the corresponding enamines 4 that reacted with hydrazine hydrate
      to yield the aminopyrazoles 5. Moreover the cyanoacetamides 2a-c reacted with a
      variety of arylidenmalononitrile to afford a novel pyrido[1,2-a]thieno[3,2
      e]pyrimidine derivatives 12a-o. In addition the enamines 4a,b reacted with
      malononitrile to afford the pyrido[1,2-a]thieno[3,2-e]pyrimidine derivatives
      19a,b. The cyanoacetamides 2a,b reacted also with salicylaldehyde to afford the
      quinoline derivatives 24a,b. Moreover the cyanoacetamides 2a,b reacted with the
      enaminones 25a-c to form the corresponding Pyridin-2-one derivatives 29a-c.
      Reactions of 2a,c with bezenediazonium chloride afford the arylhydrazones 30a,b
      that reacted with chloroacetonitrile to form the acyclic product 31 which could
      not be further cyclized to the corresponding 4-aminopyrazole. The X-ray
      crystallographic analyses of seven products could be obtained thus establishing
      with certainty the proposed structures in this work. Most of the synthesized
      compounds in this investigation were tested and evaluated as antimicrobial
      agents.

PMID- 22464426
TI  - Alignment free characterization of the influenza-A hemagglutinin genes by the
      ISSCOR method.
AB  - Analyses and visualizations by the ISSCOR method of the influenza virus
      hemagglutinin genes of three different A-subtypes revealed some rather striking
      temporal (for A/H3N3), and spatial relationships (for A/H5N1) between groups of
      individual gene subsets. The application to the A/H1N1 set revealed also
      relationships between the seasonal H1, and the swine-like novel 2009 H1v variants
      in a quick and unambiguous manner. Based on these examples we consider the
      application of the ISSCOR method for analysis of large sets of homologous genes
      as a worthwhile addition to a toolbox of genomics-it allows a rapid diagnostics
      of trends, and possibly can even aid an early warning of newly emerging
      epidemiological threats.

PMID- 22464427
TI  - The date palm (Phoenix dactylifera L.) micropropagation using completely mature
      female flowers.
AB  - This study describes an efficient and reproducible protocol for in vitro date
      palm propagation using mature female flowers. It focuses on the promising
      proliferation capacity exhibited by a number of female flower tissues taken at
      the final developmental stage. This capacity resided in the ability to preserve
      minuscule zones in a juvenile state located at the floral organ armpits (sepals
      and petals). The originality of this method lies in the possibility of
      propagation of very rare varieties, particularly the genotypes that exist in only
      one copy without the excision of the plant mother, the source of the tissue
      collected to be cultivated, which was not the case for all previous methods. The
      findings revealed that 2,4-D at 1mg/l, most of the varieties tested showed
      reactivity. The success of this technique was also noted to depend on the
      concurrent control of various factors pertaining mainly to the hormonal
      composition of the culture medium and the appropriate time of tissue transfer,
      which depends on the proliferation state as well as the culture period. This
      study describes the nature of the proliferation from the mature female flowers
      and their outcome, particularly those at the origin of embryogenic and budding
      strains and discusses the advantages of this novel multiplication method as
      compared to the currently available ones.

PMID- 22464428
TI  - Elliptical Fourier descriptors for contours in three dimensions: a new tool for
      morphometrical analysis in biology.
AB  - Elliptical Fourier descriptor analysis is a method for the morphometric study of
      curves. It has been used in the two-dimensional plane for closed contours, but
      rarely for lines in the three-dimensional space. The method consists of an
      expansion of a contour as a sum of ellipses. In this article, we study three
      dimensional contours, i.e. lines embedded in the three-dimensional space. We
      compute for the first time the relations between the Fourier coefficients and its
      geometric parameters. We then use these relations for normalization and
      reorientation of three-dimensional contours. Such an algorithm can be used to
      perform inter-individual comparisons between contours, regardless of differences
      in viewpoint or global size. Human and small animal illustrative examples using
      biomedical X-ray CT imaging data of open bone structures demonstrate the interest
      and potential of the method for morphological analysis.

PMID- 22464429
TI  - Does exogenic food benefit both partners in an ant-plant mutualism? The case of
      Cecropia obtusa and its guest Azteca plant-ants.
AB  - In the mutualisms involving the myrmecophyte Cecropia obtusa and Azteca ovaticeps
      or A. alfari, both predatory, the ants defend their host trees from enemies and
      provide them with nutrients (myrmecotrophy). A. ovaticeps provisioned with prey
      and then (15)N-enriched food produced more individuals than did control colonies
      (not artificially provisioned). This was not true for A. alfari colonies,
      possibly due to differences in the degree of maturity of the colonies for the
      chosen range of host tree sizes (less than 3m in height). Myrmecotrophy was
      demonstrated for both Azteca species as provisioning the ants with (15)N-enriched
      food translated into higher delta(15)N values in host plant tissues, indicating
      that nitrogen passed from the food to the plant. Thus, the predatory activity of
      their guest ants benefits the Cecropia trees not only because the ants protect
      them from defoliators since most prey are phytophagous insects but also because
      the plant absorbs nutrients.

PMID- 22464430
TI  - Concordance in mate choice in female mound-building mice.
AB  - Females must evaluate male quality to perform mate choice. Since females
      generally base their selection on different male features, individual females may
      differ in their choice. In this study, we show that concordance between females
      in mate choice decisions may arise without any experimental maximization of a
      particular attractive trait. Choice tests were performed in mound-building mice,
      Mus spicilegus, a monogamous species. Body odours of two male donors were
      presented to 12 female subjects individually. To determine female choice, the
      same pair of males was presented three times to a female. Four different pairs of
      male body odours were used. Male donors, not related to females, were selected at
      random in our polymorphic breeding stock. Using this two-way choice design,
      female mice displayed a clear choice and had a similar preference for particular
      males.

PMID- 22464431
TI  - The locomotor activities on sites covered by silk produced by related and
      unrelated spider mites in Tetranychus urticae (Acari: Tetranychidae).
AB  - The two-spotted spider mite Tetranychus urticae is a silk producer known to live
      in groups with a common silk web that can cover entire plants and protect mites
      against predators, rain and wind. Silk also plays an important role during
      collective migration by aerial dispersal or by walking. In this context, we
      studied the locomotor activity i.e. time in movement, in resting, and in static
      exploration (probing behaviour) of an individual confronted to clean places
      and/or places covered by silk coming from its own population or from another. Two
      populations were tested, one of the red form (Tunisia) and another of the green
      form (Belgium). The experimental results showed that the presence or the absence
      of silk did not influence the relative proportion of each behavioural item either
      for the red or the green population. Individuals of the green form population
      spent more time moving and less time resting than individuals of the red form
      population and this, whatever the substrate (red/green silk, clean). Moreover,
      the silk from the red form population attracted individuals from both
      populations, whereas the silk produced by the green form population did not
      attract any individual either from the red or the green form. This surprising
      result might have been due to a difference in the quantity and/or quality of silk
      woven by the two forms. We discuss how the differences observed in the behaviour
      of these two populations may result from differences in their strategy to rapidly
      increase the population of the colony and reinforce the silk nest.

PMID- 22464432
TI  - The genus Vietbocap Lourenco & Pham, 2010 (Scorpiones: Pseudochactidae);
      proposition of a new subfamily and description of a new species from Laos.
AB  - A new species of scorpion belonging to the family Pseudochactidae and the genus
      Vietbocap is described from the Tham Nam Lot cave, located in the Laotian part of
      the Khammouan-Ke Bang karst in Southeast Asia. Like the previously described
      species of the genus, Vietbocap lao sp. n. is a true troglobiont, but presents an
      even greater degree of adaptation to cave life, with a total lack of pigmentation
      and a very weak sclerotization of the tegument. This is the third troglobitic
      element known for the family Pseudochactidae. It represents the fifth known
      species of pseudochactid, four of which are from the Khammouan-Ke Bang karst
      system. Taking into account some marked differences between Vietbocap and the
      other two pseudochactid genera, a new subfamily, Vietbocapinae subfam. n., is
      proposed to accommodate this genus.

PMID- 22464433
TI  - Influence of ionization source design on matrix effects during LC-ESI-MS/MS
      analysis.
AB  - Glycerophosphocholines (GPChos) are known to cause matrix ionization effects
      during the analysis of biological samples (i.e. plasma, urine, etc.) in LC-MS/MS.
      In general, such matrix effect is directly related to an insufficient sample
      clean-up of the biofluids. In addition to GPCho; design of ionization source
      and/or LC also plays a very important role in matrix effects. In this research
      paper, different types of matrix effects, i.e. ion suppression or enhancement
      were observed in differently designed ion sources coupled with different LCs,
      from the same molecule, acamprosate (ACM), under the same chromatographic
      conditions. ACM was analyzed in a negative polarity in electrospray ionization
      interface using Z-spray and orthogonal spray ion source design. The analyte
      showed almost complete ion suppression in the Z-spray ionization source coupled
      with UPLC/HPLC, whereas there was very little ion enhancement in the orthogonal
      spray ionization source coupled with HPLC. In both the cases different GPChos
      were responsible, as evident from the presence of m/z 815.4 in Z-spray ion source
      and m/z 759.0 in orthogonal spray ion source. Hence, this approach can be used to
      evaluate the matrix effects in plasma samples during development and validation
      of LC-MS/MS method of drugs and their metabolites in different biological
      matrixes.

PMID- 22464434
TI  - Clinical safety and primary efficacy of bone marrow mesenchymal cell
      transplantation in subacute spinal cord injured patients.
AB  - BACKGROUND: In recent years, some studies were conducted to evaluate the effects
      of stem cells from different sources on patients with spinal cord injury (SCI).
      This study was carried out to evaluate the feasibility and therapeutic potential
      of autologous bone marrow cell (BMC) transplantation in 11 complete spinal cord
      injured patients at thoracic level. METHODS AND MATERIALS: This nonrandomized
      clinical trial compared the results of autologous BMC transplantation into
      cerebrospinal fluid (CSF) via lumbar puncture (LP) in 11 patients having complete
      SCI, with 20 patients as control group who received conventional treatment
      without BMC transplantation. The patients underwent preoperative and follow-up
      neurological assessments using the American Spinal Injury Association (ASIA)
      impairment scale. Then, the participants were followed for 12-33 months. RESULTS:
      Eleven patients with the mean age of 33.2+/-8.9 years and 20 patients with the
      mean age of 33.5+/-7.2 years were enrolled in the study and in the control group,
      respectively. None of the patients in the study and control group experienced any
      adverse reaction and complications, neither after routine treatment nor after
      cell transplantation. Five patients out of 11 (45.5%) in the study group and
      three patients in the control group (15%) showed marked recovery, but the result
      was statistically borderline (P=0.095). CONCLUSION: We conclude that
      transplantation of autologous BMC via LP is a feasible and safe technique, but at
      the moment, no clear answer can be given regarding the clinical potential,
      despite a potential tendency to treat SCI patients, observed through statistics.

PMID- 22464435
TI  - Central nervous system fungal infections: observations from a large tertiary
      hospital in northern India.
AB  - OBJECTIVE: To report our observations regarding fungal infections of the brain
      over two years from a large tertiary hospital in northern India. To identify
      fungal infections in immunocompetent and immunocompromised patients and to
      compare the two groups with respect to their age of occurrence, demographic data,
      clinical profile, radiological findings, response to treatment and outcome.
      METHODS: All consecutive cases of central nervous system (CNS) fungal infections
      admitted to the hospital over two years were included in this study. The patients
      were categorized as immunocompetent and immunocompromised, the predisposing
      factors, symptoms and clinical presentation were studied in detail and the
      outcomes of the two groups were compared. RESULTS: Of the 50 cases, 25(50%) were
      that of mucormycosis, 17(34%) were cryptococcosis and 8(16%) cases were that of
      aspergillosis. 14(28%) cases were immunocompetent and 36(72%) were
      immunocompromised. The outcome studied was as follows: 28% died of which 4% were
      HIV positive, 12% were diabetics with severe rhinorbital involvement, 2% had
      idiopathic thrombocytopenic purpura (ITP), 6% had advanced cancer and 4% had no
      predisposing illness. CONCLUSIONS: We observed fungal infections of the brain in
      both immunocompetent and immunocompromised patients. In immunocompetent patients,
      early diagnosis and appropriate treatment frequently leads to recovery from the
      illness. The mortality and morbidity of fungal infections are less in the
      immunocompetent group of patients.

PMID- 22464436
TI  - Investigation of the applicability of highly ordered TiO2 nanotube array for
      enrichment and determination of polychlorinated biphenyls at trace level in
      environmental water samples.
AB  - Present study investigated the applicability of ordered TiO(2) nanotube arrays
      for the enrichment and determination of polychlorinated biphenyls (PCBs) in water
      samples. A new and reliable method was developed for the preconcentration and
      determination of PCBs by micro-solid phase equilibrium extraction in combination
      with gas chromatography and electron capture detection (GC-ECD), which exploited
      the special physical and chemical properties of ordered TiO(2) nanotube arrays.
      The experimental results indicated that low LODs were easily achieved in the
      range of 0.02-0.10 MUg L(-1) for PCB-28, PCB-52, PCB-101, PCB-153, PCB-138, and
      PCB-180. The proposed method was validated with several real water samples, and
      good spiked recoveries have been obtained in the range of 95.8-110.5%. The
      experimental results demonstrated that TiO(2) nanotube arrays could be reused for
      over 200 times without the lost of the extraction efficiency. All these showed
      that TiO(2) nanotube arrays would be very useful in the enrichment and
      determination of trace pollutants.

PMID- 22464437
TI  - A novel hydroquinidine imprinted microsphere using a chirality-matching N
      acryloyl-L-phenylalanine monomer for recognition of cinchona alkaloids.
AB  - Using a combination of molecular imprinting technology and traditional chiral
      stationary phases, the synergistic effect between chiral monomer and chiral
      cavity of molecularly imprinted polymers in stereoselective recognition was
      investigated. We designed and synthesized an amino acid derivative to be used as
      a novel chiral functional monomer. Monodisperse molecularly imprinted core-shell
      microspheres using surface imprinting method on silica gel were prepared with
      hydroquinidine as the pseudo-template molecule for the resolution of cinchona
      alkaloids. The results showed a significant synergistic effect in stereoselective
      recognition, confirming our initial hypothesis. Furthermore, our computational
      simulation and experiments intensively support the hypothetical chiral
      recognition mechanism for the imprinted microspheres.

PMID- 22464438
TI  - Negative feedback loops: nutrient starvation employs a new tr(IKK) to inhibit
      PI3K.
AB  - The PI3K pathway promotes insulin signaling to regulate metabolism and survival
      and is subject to multiple inhibitory feedback loops. In this issue of Molecular
      Cell,Comb et al. (2012) provide evidence indicating that the PI3K pathway is
      negatively regulated in a new way: by NFkB signaling during nutrient starvation.

PMID- 22464439
TI  - PARP1 parylation promotes silent locus transmission in the nucleolus: the
      suspicion confirmed.
AB  - Parylation modulates various processes, including transcription. In this issue of
      Molecular Cell, Guetg et al. (2012) show that, in the nucleolus, PARP1-mediated
      parylation of TIP5 promotes the silencing of rDNA chromatin during replication,
      uncovering the mechanism by which PARP1 ensures that silent rDNA regions are
      properly inherited.

PMID- 22464440
TI  - R loops: lassoing DNA methylation at CpGi.
AB  - In this issue of Molecular Cell, Ginno et al. (2012) describe unusual sequence
      features at promoter CpG islands that can lead to formation of persistent RNA-DNA
      hybrids (R loops), which are proposed to prevent genomic DNA methylation.

PMID- 22464441
TI  - Preventing replication stress to maintain genome stability: resolving conflicts
      between replication and transcription.
AB  - DNA and RNA polymerases clash along the genome as they compete for the same DNA
      template. Cells have evolved specialized strategies to prevent and resolve
      replication and transcription interference. Here, we review the topology and
      architecture at sites of replication fork clashes with transcription bubbles as
      well as the regulatory circuits that control replication fork passage across
      transcribed genes. In the case of RNA polymerase II-transcribed genes,
      cotranscriptional processes such as mRNA maturation, splicing, and export
      influence the integrity of replication forks and transcribed loci. Fork passage
      likely contributes to reset the epigenetic landscape, influencing gene expression
      and transcriptional memory. When any of these processes are not properly
      coordinated, aberrant outcomes such as fork reversal and R-loop formation arise
      and trigger unscheduled recombinogenic events and genome rearrangements. The
      evolutionary implications of such conflicts on genome dynamics and their
      potential impact on oncogenic stress are discussed.

PMID- 22464442
TI  - Differences in the mechanisms of proapoptotic BH3 proteins binding to Bcl-XL and
      Bcl-2 quantified in live MCF-7 cells.
AB  - Overexpression of antiapoptotic proteins including Bcl-XL and/or Bcl-2
      contributes to tumor initiation, progression, and resistance to therapy by direct
      interactions with proapoptotic BH3 proteins. Release of BH3 proteins from
      antiapoptotic proteins kills some cancer cells and sensitizes others to
      chemotherapy. Binding of Bcl-XL and Bcl-2 to the BH3 proteins Bad, Bid, and the
      three major isoforms of Bim was measured for fluorescent protein fusions in live
      cells using fluorescence lifetime imaging microscopy and fluorescence resonance
      energy transfer. In cells the binding of the proteins at mitochondria is similar
      to the results from in vitro measurements. However, mutations in the BH3 region
      of Bim known to inhibit binding to Bcl-XL and Bcl-2 in vitro had much less effect
      in MCF-7 cells. Moreover, the BH3 mimetic ABT-737 inhibited Bad and Bid but not
      Bim binding to Bcl-XL and Bcl-2. Thus, the selectivity of ABT-737 also differs
      markedly from predictions made from in vitro measurements.

PMID- 22464443
TI  - ErbB2-driven breast cancer cell invasion depends on a complex signaling network
      activating myeloid zinc finger-1-dependent cathepsin B expression.
AB  - Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly
      linked to an invasive disease. The molecular basis of ErbB2-driven invasion is
      largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2
      positive primary human breast cancer and function as effectors of ErbB2-induced
      invasion in vitro. We identify Cdc42-binding protein kinase beta, extracellular
      regulated kinase 2, p21-activated protein kinase 4, and protein kinase C alpha as
      essential mediators of ErbB2-induced cysteine cathepsin expression and breast
      cancer cell invasiveness. The identified signaling network activates the
      transcription of cathepsin B gene (CTSB) via myeloid zinc finger-1 transcription
      factor that binds to an ErbB2-responsive enhancer element in the first intron of
      CTSB. This work provides a model system for ErbB2-induced breast cancer cell
      invasiveness, reveals a signaling network that is crucial for invasion in vitro,
      and defines a specific role and targets for the identified serine-threonine
      kinases.

PMID- 22464444
TI  - An analysis of fine needle aspiration versus core needle biopsy in clinically
      palpable breast lesions: a report on the predictive values and a cost comparison.
AB  - BACKGROUND: Although fine-needle aspiration (FNA) is an established tool in the
      biopsy of breast masses, there has been a trend toward using core-needle biopsy
      (CNB). The aim of this study was to determine whether FNA has comparable
      predictive value with CNB and whether FNA is more cost effective. METHODS: A
      retrospective review was conducted on 162 patients who underwent either FNA or
      CNB of palpable breast lesions and had histologic confirmation with surgical
      biopsy in calendar year 2005. RESULTS: There were no false-positives or false
      negatives in either group. The sensitivity, specificity, and positive predictive
      value for FNA were 89%, 98%, and 94%, respectively. CNB had sensitivity,
      specificity, and positive predictive value of 100%, 90%, and 93%, respectively.
      The cost to perform FNA was $166.34, compared with $477.92 for CNB. CONCLUSIONS:
      FNA and CNB had comparable predictive value, with FNA being more cost effective.

PMID- 22464447
TI  - Isolated hepatic perfusion for the treatment of liver metastases.

PMID- 22464445
TI  - Positron emission tomography in hepatobiliary and pancreatic malignancies: a
      review.
AB  - BACKGROUND: The prognosis for hepatobiliary and pancreatic malignancies is
      dismal. Surgery remains the primary curative option, but unresectable disease is
      often discovered during operative exploration. Positron emission tomography (PET)
      provides unique biological information different from current imaging modalities.
      The role of PET in detecting hepatobiliary and pancreatic malignancies has not
      yet been established. The purpose of this article was to review the literature on
      the use of PET in hepatobiliary and pancreatic malignancies. DATA SOURCES: We
      performed an extensive search on PubMed using PET and hepatocellular, pancreatic,
      gallbladder, and cholangiocarcinoma as keywords, excluding articles not written
      in English or on nonhuman subjects, case reports, and series with <5 patients.
      CONCLUSIONS: Although PET has shown usefulness in the diagnosis of certain
      cancers, current literature cautions against the use of PET for determining
      malignant potential of primary liver and pancreatic lesions. Literature on PET
      more strongly supports clinical roles for restaging of hepatobiliary and
      pancreatic malignancies, and for identifying metastatic disease.

PMID- 22464448
TI  - Postprandial expression of growth-related genes in Atlantic salmon (Salmo salar
      L.) juveniles fasted for 1 week and fed a single meal to satiation.
AB  - We investigated postprandial changes in transcript abundance following a single
      satiating meal in juvenile Atlantic salmon (Salmo salar L.) (about 70 g body
      mass) following fasting for 1 week at 12 degrees C. The expression of twenty
      three growth-related genes was determined in fast myotomal muscle using
      quantitative real-time PCR at the following postprandial time points: - 12, 0, 1,
      3, 6, 12, 24, 48 and 96 h. The gut was fullest 1-6 h after feeding and emptied
      within 48-96 h. IGF-I, MyoD1c, MRF4 and myf5 transcripts were sharply up
      regulated within 1 h of refeeding and are promising candidate genes involved in a
      fast-response signalling system that regulates fish myotomal muscle growth. These
      genes clustered together with MyoD1b and suggest a coordinated regulation to
      favour resumption of myogenesis as an early response to feeding. Insulin-like
      growth factor (IGF)-II and the ubiquitin ligase MAFbx/atrogin-1 were initially
      down-regulated but restored to initial values after 12 h. It is also suggested
      that local production of IGF-I within the muscle might suppress catabolic
      pathways depressing MAFbx/atrogin-1.

PMID- 22464449
TI  - Progressive visual loss in a pregnant woman with idiopathic intracranial
      hypertension.

PMID- 22464451
TI  - Hypnotic modulation of pain perception and of brain activity triggered by
      nociceptive laser stimuli.
AB  - INTRODUCTION: Neuroimaging studies indicate that hypnotic suggestions of
      increased and decreased pain intensity and unpleasantness may modulate
      somatosensory and cingulate cortex activity, respectively. METHODS: Using a
      within subject design and a strict subject selection procedure, we tested in High
      (Highs) and Low (Lows) hypnotically suggestible individuals whether hypnotic
      suggestions of sensory and affective hypoalgesia or hyperalgesia differentially
      affected subjective ratings of laser-induced pain and nociceptive-related brain
      activity in the time- and time-frequency domain. RESULTS: Hypnotic modulation of
      pain intensity and unpleasantness affected subjective ratings of laser-induced
      pain only in Highs. Such modulation was more specific for unpleasantness
      manipulation and more evident for suggestions of hyperalgesia. Importantly, Highs
      and Lows showed increase and decrease of P2a and P2b wave amplitudes and gamma
      band power, respectively. CONCLUSIONS: Hypnotic suggestions exerted a top-down
      modulatory effect on both evoked and induced-cortical brain responses triggered
      by selective nociceptive laser inputs. Furthermore, correlation analyses
      indicated that gamma power modulation and suggestions of hyperalgesia may reflect
      the process of allocating control resources to salient and threatening sensory
      affective dimensions of pain.

PMID- 22464450
TI  - A novel function of IL-2: chemokine/chemoattractant/retention receptor genes
      induction in Th subsets for skin and lung inflammation.
AB  - The Foxp3(+)CD4(+) regulatory T-cell (Treg)-deficient Scurfy (Sf) mice rapidly
      develop severe inflammation in the skin and lungs with expanded Th subsets
      bearing increased expression of various chemokine/chemoattractant/retention
      receptor genes (CRG). Nine different double mutants were generated to elucidate
      their roles in the skin and lung inflammation. The expanded Th2 response and the
      increased expression of several CRG for the skin and lung inflammation were
      inhibited in Sf.Il2(-/-) mice as previously described using microarray analysis.
      Herein in a reciprocal approach, we demonstrated that Sf.Il4(-/-) and Sf.Stat6(-/
      ) mice, despite lacking Th2 cytokines IL-4, IL-5, and IL-13, as well as the IL
      4/STAT6-dependent CRG expression, the inflammation in the skin and lungs
      remained. The effect of the other Th1 cytokine IFN-gamma was studied in Sf.Ifng(
      /-) mice in which the multi-organ inflammation (MOI) was delayed but fully
      developed afterward with enhanced CRG expression except for the IFN-gamma
      dependent Cxcr3 in CD4(+) T-cells. Similarly, a transient delay of MOI was
      observed for Sf.Itgae(-/-) mice but their Th subsets and the critical CRG
      expansion remained. Ltb4r1(-/-), Alox5(-/-), Cx3cr1(gfp/gfp), or Il10(-/-) mutant
      genes also failed to effectively block inflammation in the skin and lungs in Sf
      mice. Our study has identified a novel function of IL-2 as a powerful Th1
      cytokine that induces a panel of CRG in Th subsets required for skin and lung
      inflammation in Sf mice. The CRG panel induced by IL-2 but not by IL-4 or IFN
      gamma explains the apparent "organ-specific" display of the skin and lung
      inflammation in Sf mice.

PMID- 22464452
TI  - Atlas-based automatic mouse brain image segmentation revisited: model complexity
      vs. image registration.
AB  - Although many atlas-based segmentation methods have been developed and validated
      for the human brain, limited work has been done for the mouse brain. This paper
      investigated roles of image registration and segmentation model complexity in the
      mouse brain segmentation. We employed four segmentation models [single atlas,
      multiatlas, simultaneous truth and performance level estimation (STAPLE) and
      Markov random field (MRF) via four different image registration algorithms
      (affine, B-spline free-form deformation (FFD), Demons and large deformation
      diffeomorphic metric mapping (LDDMM)] for delineating 19 structures from in vivo
      magnetic resonance microscopy images. We validated their accuracies against
      manual segmentation. Our results revealed that LDDMM outperformed Demons, FFD and
      affine in any of the segmentation models. Under the same registration, increasing
      segmentation model complexity from single atlas to multiatlas, STAPLE or MRF
      significantly improved the segmentation accuracy. Interestingly, the multiatlas
      based segmentation using nonlinear registrations (FFD, Demons and LDDMM) had
      similar performance to their STAPLE counterparts, while they both outperformed
      their MRF counterparts. Furthermore, when the single-atlas affine segmentation
      was used as reference, the improvement due to nonlinear registrations (FFD,
      Demons and LDDMM) in the single-atlas segmentation model was greater than that
      due to increasing model complexity (multiatlas, STAPLE and MRF affine
      segmentation). Hence, we concluded that image registration plays a more crucial
      role in the atlas-based automatic mouse brain segmentation as compared to model
      complexity. Multiple atlases with LDDMM can best improve the segmentation
      accuracy in the mouse brain among all segmentation models tested in this study.

PMID- 22464453
TI  - A semiautomatic postprocessing of liver R2* measurement for assessment of liver
      iron overload.
AB  - PURPOSE: The purpose was to propose and evaluate a semiautomatic postprocessing
      method to measure liver R2(*) values in patients with a broad range of liver iron
      content. MATERIALS AND METHODS: Multiecho gradient echo magnetic resonance images
      were acquired in patients diagnosed with thalassemia or other types of congenital
      anemias. Liver R2(*) values were measured using a routine manually defined region
      of-interest (mROI) method and a semiautomatic (SA) method. In the semiautomatic
      method, pixelwise (pSA) and averaged (aSA) signal fitting was performed on the
      segmented liver tissues after hepatic vessel extraction. The pixelwise fitting
      approach resulted in a liver R2(*) map with an overlay of nonfitted pixels
      associated with noise performance. The following aSA approach derived overall
      R2(*) by fitting the averaged signal intensities of all pixels within the liver
      ROI excluding vessels and nonfitted pixels. The measurement accuracy and
      interobserver agreement using mROI and the two semiautomatic approaches (pSA and
      aSA) were evaluated. RESULTS: In a total of 45 exams with R2(*) ranging from 30
      to 1500 s(-1), the R2(*) measurements using all three methods were overall highly
      correlated and concordant with each other. R2(*) values measured by aSA were
      consistently higher than those measured by mROI. At lower R2(*) (<1000 s(-1)),
      R2(*) values measured by pSA were consistent with aSA but higher than mROI; with
      increasing R2(*), the pSA method became less stable and underestimated R2(*) due
      to increased noise level. The interobserver agreement was higher for the aSA
      method compared to pSA and mROI. CONCLUSION: The semiautomatic postprocessing
      method provides a promising tool for reliable liver R2(*) measurement with
      additional information for overall evaluation of iron distribution and
      measurement confidence. This method may offer the potential of reducing
      interoperator variability and improving diagnostic confidence in patients with
      liver iron overload.

PMID- 22464454
TI  - Anti-NMDA receptor encephalitis: the importance of early diagnosis and aggressive
      immunotherapy in tumor negative pediatric patients.

PMID- 22464455
TI  - Effects of midazolam and lidocaine on spectral properties of the EEG in full-term
      neonates with stroke.
AB  - Assessment of the neonatal EEG may be hampered by drug-specific changes in
      electrocortical activity. To quantify effects of a loading dose of midazolam and
      lidocaine on the EEG frequency spectrum of full-term neonates with perinatal
      arterial ischemic stroke (PAIS), 11 full-term infants underwent multi-channel
      amplitude-integrated EEG (aEEG) and EEG recordings. During recording, midazolam
      and/or lidocaine were administered as anti-epileptic drug. Retrospectively, we
      performed spectral analysis on 4-h EEG segments around the loading dose. The
      frequency spectrum was divided in delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz)
      and beta (13-30 Hz) bands. Midazolam induced immediate suppression of the aEEG
      background pattern for 30-60 min. Spectral EEG analysis showed decreased total
      and absolute frequency band powers. Relative delta power decreased, theta power
      increased while alpha and beta powers remained constant. Lidocaine induced no
      aEEG background pattern suppression. Total and absolute EEG band powers were
      unchanged. Relative delta power decreased, theta and alpha power increased and
      beta power remained constant. Effects of lidocaine were more pronounced in the
      stroke-affected hemisphere. In conclusions, both drugs induced a shift from low
      to higher frequency electrocortical activity. Additionally, midazolam reduced
      total EEG power. These spectral changes differ from those seen in adult studies.

PMID- 22464456
TI  - X-ray crystallographic structure-based design of selective thienopyrazole
      inhibitors for interleukin-2-inducible tyrosine kinase.
AB  - Beginning with a screening hit, unique thienopyrazole-indole inhibitors of Itk
      (interleukin-2-inducible tyrosine kinase) were designed, synthesized, and
      crystallized in the target kinase. Although initial compounds were highly active
      in Itk, they were not selective. Increasing the steric bulk around a tertiary
      alcohol at the 5-indole position dramatically improved selectivity toward Lyk and
      Syk, but not Txk. Substitutions at the 3- and 4-indole positions gave less active
      compounds that remained poorly selective. A difluoromethyl substitution at the 5
      position of the thienopyrazole led to a highly potent and selective compound.
      Phenyl at this position reduced activity and selectivity while pushing the side
      chains of Lys-391 and Asp-500 away from the binding pocket. Novel and selective
      thienopyrazole inhibitors of Itk were designed as a result of combining structure
      based design and medicinal chemistry.

PMID- 22464457
TI  - In silico binding free energy predictability with pi-pi interaction energy
      augmented scoring function: benzimidazole Raf inhibitors as a case study.
AB  - The ability to estimate binding affinities of ligands precisely is of paramount
      importance in designing drugs. Docking programs are used primarily to predict the
      binding mode of ligands to receptors. However, current scoring functions as used
      in docking programs are not reliable enough to predict binding affinities of
      ligands without any further calculations. In the present study, we investigate
      the usefulness of adding pi-pi interaction energies between ring groups of
      residues and ligands to the scoring function for docking. It is found that such
      addition helps ranking ligand activities more correctly. LMP2 calculation is used
      to measure pi-pi interaction energies between ring groups. The result of this
      simple addition shows possibility of pi-pi interaction generalization in scoring
      functions.

PMID- 22464458
TI  - Novel acridinedione derivatives: design, synthesis, SIRT1 enzyme and tumor cell
      growth inhibition studies.
AB  - A new scaffold N-(9-(ortho/meta/para-(benzyloxy)phenyl)-3,3,6,6-tetramethyl-1,8
      dioxo-1,2,3,4,5,6,7,8-octahydroacridin-10(9H)-yl) isonicotinamide (H1-3) was
      discovered as a hSIRT1 inhibitor through virtual screening of in-house database.
      Based on these hits, a library of compounds were designed, synthesized and tested
      for in vitro hSIRT1 activity. The most potent compound 4d in the series showed a
      significant inhibition of SIRT1 activity. Further antitumor studies of compound
      4d, showed a dose dependent increase in acetylation of p53K382 and decrease in
      SIRT1 with an IC(50) of 0.25 MUM in MDA-MB231 breast cancer cell lines.
      Individual 3D-QSAR analysis using Schrodinger showed distribution of hydrophobic
      and non polar positive co-efficient at ortho position essential for bioactivity
      based on 4d.

PMID- 22464459
TI  - Invited commentary.

PMID- 22464460
TI  - Invited commentary.

PMID- 22464461
TI  - Revascularization of midaortic dysplastic syndrome.

PMID- 22464462
TI  - Discontent with operative consent.

PMID- 22464463
TI  - Invited commentary.

PMID- 22464465
TI  - Regarding "primary aortoenteric fistula following endovascular aortic repair due
      to type II endoleak".

PMID- 22464467
TI  - Regarding "ultrasound-guided infraclavicular brachial plexus block enhances
      postoperative blood flow in arteriovenous fistulas".

PMID- 22464469
TI  - [The blues: a growing trend?].

PMID- 22464471
TI  - Dicentric chromosome formation and epigenetics of centromere formation in plants.
AB  - Plant centromeres are generally composed of tandem arrays of simple repeats that
      form a complex chromosome locus where the kinetochore forms and microtubules
      attach during mitosis and meiosis. Each chromosome has one centromere region,
      which is essential for accurate division of the genetic material. Recently,
      chromosomes containing two centromere regions (called dicentric chromosomes) have
      been found in maize and wheat. Interestingly, some dicentric chromosomes are
      stable because only one centromere is active and the other one is inactivated.
      Because such arrays maintain their typical structure for both active and inactive
      centromeres, the specification of centromere activity has an epigenetic component
      independent of the DNA sequence. Under some circumstances, the inactive
      centromeres may recover centromere function, which is called centromere
      reactivation. Recent studies have highlighted the important changes, such as DNA
      methylation and histone modification, that occur during centromere inactivation
      and reactivation.

PMID- 22464470
TI  - Current advances in epigenetic modification and alteration during mammalian
      ovarian folliculogenesis.
AB  - During the growth and development of mammalian ovarian follicles, the activation
      and deactivation of mass genes are under the synergistic control of diverse
      modifiers through genetic and epigenetic events. Many factors regulate gene
      activity and functions through epigenetic modification without altering the DNA
      sequence, and the common mechanisms may include but are not limited to: DNA
      methylation, histone modifications (e.g., acetylation, deacetylation,
      phosphorylation, methylation, and ubiquitination), and RNA-associated silencing
      of gene expression by noncoding RNA. Over the past decade, substantial progress
      has been achieved in studies involving the epigenetic alterations during
      mammalian germ cell development. A number of candidate regulatory factors have
      been identified. This review focuses on the current available information of
      epigenetic alterations (e.g., DNA methylation, histone modification, noncoding
      RNA-mediated regulation) during mammalian folliculogenesis and recounts when and
      how epigenetic patterns are differentially established, maintained, or altered in
      this process. Based on different types of epigenetic regulation, our review
      follows the temporal progression of events during ovarian folliculogenesis and
      describes the epigenetic changes and their contributions to germ cell-specific
      functions at each stage (i.e., primordial folliculogenesis (follicle formation),
      follicle maturation, and follicular atresia).

PMID- 22464472
TI  - Evaluating the phylogenetic position of Chinese tree shrew (Tupaia belangeri
      chinensis) based on complete mitochondrial genome: implication for using tree
      shrew as an alternative experimental animal to primates in biomedical research.
AB  - Tree shrew (Tupaia belangeri) is currently placed in Order Scandentia and has a
      wide distribution in Southeast Asia and Southwest China. Due to its unique
      characteristics, such as small body size, high brain-to-body mass ratio, short
      reproductive cycle and life span, and low-cost of maintenance, tree shrew has
      been proposed to be an alternative experimental animal to primates in biomedical
      research. However, there are some debates regarding the exact phylogenetic
      affinity of tree shrew to primates. In this study, we determined the mtDNA entire
      genomes of three Chinese tree shrews (T. belangeri chinensis) and one Malayan
      flying lemur (Galeopterus variegatus). Combined with the published data for
      species in Euarchonta, we intended to discern the phylogenetic relationship among
      representative species of Dermoptera, Scandentia and Primates. The mtDNA genomes
      of Chinese tree shrews and Malayan flying lemur shared similar gene organization
      and structure with those of other mammals. Phylogenetic analysis based on 12
      concatenated mitochondrial protein-encoding genes revealed a closer relationship
      between species of Scandentia and Glires, whereas species of Dermoptera were
      clustered with Primates. This pattern was consistent with previously reported
      phylogeny based on mtDNA data, but differed from the one reconstructed on the
      basis of nuclear genes. Our result suggested that the matrilineal affinity of
      tree shrew to primates may not be as close as we had thought. The ongoing project
      for sequencing the entire genome of Chinese tree shrew will provide more
      information to clarify this important issue.

PMID- 22464473
TI  - The altered responses of a new mutant long life span 1 to cytokinin in
      Arabidopsis thaliana.
AB  - Cytokinins are a class of essential plant hormones regulating plant growth and
      development. Although the two-component phosphorelay pathway of cytokinin has
      been well characterized, the intact cytokinin responses regulation picture still
      needs to be fully depicted. Here we report a new mutant, long life span 1 (lls1),
      which displays dwarf stature, curled leaves, numerous axillary branches and
      nearly 5-month life span. Exogenous cytokinin could not recover the phenotypes of
      the mutant. Moreover, mutation in lls1 suppressed the cytokinin-responsive
      phenotypes, including root and hypocotyl growth inhibition, anthocyanin
      accumulation, metaxylem promotion in primary root development. The induction of
      cytokinin-responsive genes, ARR5, AHP5, and CKX3, was also suppressed in lls1.
      According to quantitative RT-PCR (qRT-PCR) and microarray results, the basal
      expression of positive factors AHP5, ARR1, and ARR10 were down-regulated, while
      the negative factors ARR4 and ARR5 were up-regulated. Our results suggested that
      LLS1 gene might be involved in the regulation of cytokinin signaling. It was
      mapped to chromosome 4 where no other cytokinin relevant gene has been reported.

PMID- 22464474
TI  - The upregulation of NtAN2 expression at low temperature is required for
      anthocyanin accumulation in juvenile leaves of Lc-transgenic tobacco (Nicotiana
      tabacum L.).
AB  - Anthocyanins often accumulate in plants subjected to environmental stress,
      including low temperature. However, the molecular regulatory mechanism of
      anthocyanin biosynthesis at low temperature is largely unknown. Here, tobacco was
      transformed with a maize anthocyanin regulatory gene Lc driven by AtSPX3 promoter
      to investigate the effect of Lc upon the anthocyanin-biosynthesis pathway. We
      found that the anthocyanin-biosynthesis pathway could not be activated in wild
      type, while Lc-transgenic tobacco lines exhibited purple pigmentation in juvenile
      leaves at low temperature. Accordingly, the total anthocyanin contents increased
      specifically in juvenile leaves in Lc-transgenic lines. Transcriptional analysis
      showed that NtCHS and NtCHI were induced by low temperature in leaves of wild
      type and transgenic lines. NtDFR was uniquely expressed in Lc-transgenic lines,
      but its transcript was not detected in wild type, implying that NtDFR expression
      in tobacco leaves was dependent on Lc. Furthermore, the expression of NtAN2
      (regulatory gene) and NtANS (anthocyanidin synthase gene) was coordinately
      upregulated in Lc-transgenic lines under low temperature, suggesting that both Lc
      and NtAN2 might activate the expression of NtANS. Based on our findings and
      previous reports, we postulated that Lc interacted with NtAN2 induced by low
      temperature stress and consequently stimulated anthocyanin biosynthesis in
      juvenile leaves of Lc-transgenic tobacco lines.

PMID- 22464475
TI  - "De novo" biventricular pacing in two children with complete atrio-ventricular
      block and severe ventricular dilatation: early reverse remodeling.

PMID- 22464476
TI  - The effect of CD137-CD137 ligand interaction on the expression of NFATc1 in
      apolipoprotein E-deficient mice.

PMID- 22464477
TI  - Clinical outcomes of zotarolimus-eluting stents versus the first generation
      sirolimus-eluting stents and paclitaxel-eluting stents: a meta-analysis of
      randomized trials.

PMID- 22464478
TI  - No consistent evidence of differential cardiovascular risk amongst proton-pump
      inhibitors when used with clopidogrel: meta-analysis.
AB  - BACKGROUND: Data from pharmacokinetic and pharmacodynamic studies indicate that
      the adverse clopidogrel-proton pump inhibitor (PPI) interaction may vary between
      PPIs, with pantoprazole considered relatively less problematic. We aimed to
      evaluate systematically whether individual PPIs differ in their risk for
      cardiovascular events when concomitantly administered with clopidogrel. METHODS:
      We searched MEDLINE, EMBASE and Cochrane Trials Register up to December 2011 for
      randomized and non-randomized studies that reported adverse cardiovascular events
      with exposure to specific PPIs in patients receiving clopidogrel. We performed
      random effects meta-analysis, and assessed heterogeneity using the I(2)
      statistic. RESULTS: A total of 23 studies with 222,311 participants were
      included. Meta-analysis of major adverse cardiovascular events was mostly limited
      by moderate-substantial heterogeneity. Pooled estimates of cardiovascular risk
      were significantly elevated for individual PPIs such as omeprazole, esomeprazole,
      lansoprazole, and pantoprazole when used with clopidogrel. However, meta-analysis
      of adverse cardiovascular risk in seven observational studies reporting on PPI
      therapy alone (without concomitant clopidogrel) also found an elevated odds ratio
      of 1.28 (95% CI 1.14-1.44) compared with no clopidogrel/no PPI exposure. Meta
      analysis of two randomized controlled trials did not show significant adverse
      cardiovascular effect from omeprazole or esomeprazole. CONCLUSIONS: The absence
      of consistent evidence on differential cardiovascular risk amongst PPIs
      (particularly regarding safety of pantoprazole) is in direct opposition to the
      platelet function and pharmacokinetic data. Our findings of increased
      cardiovascular risk with PPIs in the absence of clopidogrel suggest that
      confounding and bias are strong possibilities. The clinical validity or relevance
      of the hypothesized PPI-clopidogrel interaction remains questionable.

PMID- 22464479
TI  - Implications of pre-procedural TIMI flow in patients with non ST-segment
      elevation acute coronary syndromes undergoing percutaneous coronary
      revascularization: insights from the ACUITY trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prognostic implications
      of preprocedural TIMI flow in ACS patients undergoing early invasive management.
      BACKGROUND: Although the negative prognostic impact of reduced Thrombolysis in
      Myocardial Infarction (TIMI) flow before percutaneous coronary intervention (PCI)
      in ST-segment elevation myocardial infarction (STEMI) has been well described,
      whether this relationship holds in patients with acute coronary syndromes (ACS;
      unstable angina and non-STEMI) has not been examined. METHODS: We evaluated 3582
      moderate and high-risk patients with ACS undergoing PCI enrolled in the ACUITY
      trial. Patients were divided in 3 groups according to pre-procedural culprit
      vessel TIMI flow (TIMI 0/1, TIMI 2 and TIMI 3 flows), determined by an
      independent angiographic core laboratory. RESULTS: Baseline culprit vessel flow
      was absent (TIMI 0/1) in 453 patients (12.6%), reduced (TIMI 2) in 389 patients
      (10.9%) and normal (TIMI 3) in 2740 patients (76.5%) patients. Post-PCI TIMI 3
      flow was achieved in 87.2%, 86.8% and 98.8% of the 3 groups, respectively
      (P<0.0001). At 1 year, mortality occurred in 2.7%, 2.4% and 3.0% of patients with
      baseline TIMI 0/1, 2 and 3 flows, respectively (P=0.82). By multivariable
      analysis, pre-PCI TIMI flow 0/1 (vs. TIMI 3) was not an independent predictor of
      1-year mortality (P=0.61). CONCLUSIONS: Reduced baseline TIMI flow in moderate
      and high-risk patients with ACS undergoing PCI does not appear to affect survival
      at 1 year, in contrast to that described in patients with STEMI.

PMID- 22464480
TI  - Protective effects of valsartan against cigarette smoke-induced left ventricular
      systolic dysfunction in rats.
AB  - OBJECTIVES: To investigate the protective effects of valsartan against smoking
      induced left ventricular dysfunction and explore the potential mechanisms
      involved. METHODS: Rats were randomly divided into 3 groups: smoking group
      (exposed to cigarette smoke), valsartan group (exposed to cigarette smoke and
      treated orally with valsartan), and control group. Transthoracic echocardiography
      was performed to evaluate left ventricular systolic and diastolic function.
      Oxidative stress was evaluated by detecting malondialdehyde (MDA), superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px) in the supernatant of left
      ventricular tissue. Cardiomyocyte apoptotic rate was determined by flow cytometry
      with Annexin V/PI staining. Serum levels of high-sensitivity C-reactive protein
      (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), and monocyte
      chemotactic protein-1 (MCP-1) were detected to reflect the extent of systemic
      inflammation. RESULTS: The echocardiographic data indicated that valsartan has
      protective effects against cigarette smoke-induced left ventricular systolic
      dysfunction (LVSD). Our findings showed a significant decrease in MDA level and
      increases in SOD and GSH-Px activities in the valsartan group compared to the
      smoking group. The apoptotic rate in the valsartan group was significantly lower
      than in the smoking group. The concentrations of hs-CRP, IL-6, TNF-alpha and MCP
      1 in the valsartan group were significantly lower than in the smoking group.
      CONCLUSIONS: Our study demonstrates that valsartan has protective effects against
      smoking-induced LVSD by attenuating oxidative stress, apoptosis, and
      inflammation.

PMID- 22464481
TI  - Heart failure-induced skeletal myopathy in spontaneously hypertensive rats.
AB  - BACKGROUND: Although skeletal muscle atrophy and changes in myosin heavy chain
      (MyHC) isoforms have often been observed during heart failure, their
      pathophysiological mechanisms are not completely defined. In this study we tested
      the hypothesis that skeletal muscle phenotype changes are related to myogenic
      regulatory factors and myostatin/follistatin expression in spontaneously
      hypertensive rats (SHR) with heart failure. METHODS: After developing tachypnea,
      SHR were subjected to transthoracic echocardiogram. Pathological evidence of
      heart failure was assessed during euthanasia. Age-matched Wistar-Kyoto (WKY) rats
      were used as controls. Soleus muscle morphometry was analyzed in histological
      sections, and MyHC isoforms evaluated by electrophoresis. Protein levels were
      assessed by Western blotting. STATISTICAL ANALYSIS: Student'st test and Pearson
      correlation. RESULTS: All SHR presented right ventricular hypertrophy and seven
      had pleuropericardial effusion. Echocardiographic evaluation showed dilation in
      the left chambers and left ventricular hypertrophy with systolic and diastolic
      dysfunction in SHR. Soleus weight and fiber cross sectional areas were lower (WKY
      3615 +/- 412; SHR 2035 +/- 224 MUm(2); P<0.001), and collagen fractional volume
      was higher in SHR. The relative amount of type I MyHC isoform was increased in
      SHR. Myogenin, myostatin, and follistatin expression was lower and MRF4 levels
      higher in SHR. Myogenin and follistatin expression positively correlated with
      fiber cross sectional areas and MRF4 levels positively correlated with I MyHC
      isoform. CONCLUSION: Reduced myogenin and follistatin expression seems to
      participate in muscle atrophy while increased MRF4 protein levels can modulate
      myosin heavy chain isoform shift in skeletal muscle of spontaneously hypertensive
      rats with heart failure.

PMID- 22464482
TI  - Relationship of ECG findings to phenotypic expression in patients with
      hypertrophic cardiomyopathy: a cardiac magnetic resonance study.
AB  - BACKGROUND: The 12-lead electrocardiogram (ECG) is considered an essential
      screening tool for hypertrophic cardiomyopathy (HCM). A vast array of ECG
      abnormalities has been described in HCM, although their relationship to left
      ventricle (LV) morphology and degree of hypertrophy appears elusive. Aim of this
      study was to assess the relationship of ECG patterns with the HCM phenotype
      assessed according to the novel opportunities offered by cardiac magnetic imaging
      (CMR). METHODS: CMR and 12-lead ECG were performed in 257 HCM patients. Severity
      of ECG abnormalities was defined by the sum of 9 criteria: abnormal cardiac
      rhythm, QRS duration >= 100 ms, Romhilt-Estes score >= 5, fascicular block (LAHB)
      and/or bundle-branch block (LBBB or RBBB), ST-T abnormalities, ST-T segment
      elevation >= 0.2 mV, prolonged QTc interval, pathological Q waves, absence of
      normal Q wave. Four ECG groups were identified: normal (0 criteria); mildly
      abnormal (1-3 criteria); moderately abnormal (4-6 criteria); markedly abnormal (7
      9 criteria). RESULTS: There was a direct relationship between severity of ECG
      abnormalities and HCM phenotype. LV mass index was normal in most patients with
      normal ECG and progressively increased with each class of ECG score, from 70.9 +/
      18.6g/m(2) in patients with normal ECG to 107.1 +/- 55.1g/m(2) among those with
      markedly abnormal ECG (p=<0.0001). Likewise, the prevalence and extent of late
      gadolinium enhancement (LGE) increased significantly with the ECG score, from 37%
      in patients with normal ECG to 93% in patients with markedly abnormal ECG
      (overall p=0.0012). A normal ECG had a negative predictive accuracy of 96% for
      markedly increased LV mass (>91 g/m(2) for men and >69 g/m(2) for women), and of
      100% for maximum LV thickness >= 30 mm. CONCLUSIONS: In a large HCM cohort, the
      number and severity of ECG abnormalities were directly related to phenotypic
      expression as revealed by CMR. Although false negative ECG findings remain a
      challenge in population screenings for HCM, a normal ECG proved effective in
      ruling out severe LV hypertrophy, suggesting potential implications for long-term
      follow-up of HCM patients and family members. A simple score for quantification
      of ECG abnormalities in HCM patients is proposed.

PMID- 22464483
TI  - Young girl with apical ballooning heart syndrome.

PMID- 22464484
TI  - TIMI frame count versus thermodilution: diagnosing microvascular angina in
      cardiac syndrome X.

PMID- 22464485
TI  - Valvulopathies in sub-Saharan African children: patterns, humanitarian
      interventions and cardiac surgical problems.
AB  - Despite the high burden of rheumatic fever in sub-Saharan African, there is
      currently no sustained and comprehensive strategy to control the disease.
      Consequently in this area the number of patients affected by rheumatic valve
      disease (RVD), most with a surgical indication, is 10-20 fold higher than in
      industrialised countries and estimates indicate that more than 50% of African RVD
      patients will die before age 25. In this paper, we review clinical and management
      issues of RVD in children in sub-Saharan Africa. Severe heart failure and
      undergrowth are the prevalent presentation of the illness. Severe mitral
      regurgitation is the commonest rheumatic valvulopathy observed in the first and
      second decades. Valve repair, the approach of choice, may be associated with
      unfavourable outcomes in patients with extreme cardiomegaly. In young people,
      whenever correct anticoagulation may reasonably be achieved, mechanical mitral
      prostheses should be preferred, even in females. The early deterioration of
      biologic mitral prostheses strongly suggests limiting their use to those cases in
      which correct anticoagulation is not feasible. In most sub-Saharan countries,
      socioeconomic factors strongly limit access to health services and to cardiac
      surgery in particular. Efforts to overcome these barriers have resulted in
      humanitarian projects along two patterns: creation of high tech on site health
      care structures or transfer of children with complex diseases to receive highly
      specialised cardiac surgical care abroad. We summarise the experience of our
      programme that followed the latter approach.

PMID- 22464486
TI  - Heterozygous familial hypercholesterolemia in Hong Kong Chinese. Study of 252
      cases.
AB  - BACKGROUND: Earlier studies reported that Chinese subjects with heterozygous
      familial hypercholesterolemia (heFH) living in Mainland China or in Western
      countries had lower plasma low-density lipoprotein cholesterol (LDL-C) levels and
      lower prevalence of xanthomata or coronary heart disease (CHD) than Caucasians
      with heFH and a greater proportion went unrecognized. We characterized the
      features of Hong Kong Chinese with heFH identified by cascade screening. METHODS:
      Potential probands with primary hypercholesterolemia manifesting total
      cholesterol (TC) greater than 7.5 mmol/L or LDL-C greater than 4.9 mmol/L were
      selected from a lipid clinic in a public hospital in Hong Kong. After screening
      of 132 unrelated potential probands and their relatives, 252 subjects from 87
      pedigrees were clinically diagnosed as heFH. RESULTS: In 252 heFH patients (mean
      age 37 +/- 17 years, 100 males), the plasma TC and LDL-C were 9.1 +/- 1.5 mmol/L
      and 7.2 +/- 1.5 mmol/L, respectively. In subjects aged >= 18 years, the
      prevalence of xanthomata and corneal arcus was 40.6% and 81.2% in males, and
      54.8% and 66.9% in females respectively. The overall incidence of CHD was 9.9% in
      males and 8.5% in females in patients aged over 18 years with CHD history
      available. Multiple logistic regression analysis showed that advanced age and
      presence of xanthelasmata were significantly associated with increased risk of
      CHD. CONCLUSIONS: This study is the first to characterize the epidemiologic
      features of heFH in Hong Kong Chinese, which provides new population-specific
      information on this genetic disorder. This may presage how this condition will
      manifest in China in the near future.

PMID- 22464487
TI  - Trends in stroke incidence after hospitalization for atrial fibrillation in
      Sweden 1987 to 2006.
AB  - BACKGROUND: To investigate recent trends in incidence of hemorrhagic and non
      hemorrhagic strokes in patients with atrial fibrillation (AF). METHODS: The
      Swedish Hospital Discharge and Cause of Death Registries were linked to provide
      outcome data. RESULTS: 321,276 patients 35 to 84 years (56.5% male, mean age 71.5
      years) free of prior stroke with a first AF diagnosis during 1987-2006 were
      included. Over 3 year follow-up 24,733 patients (7.7%) were diagnosed with
      ischemic stroke and 2292 (0.7%) with hemorrhagic stroke. The 3-year incidence of
      ischemic stroke decreased from 8.7% for patients diagnosed in 1987-1991 to 6.6%
      for those diagnosed in 2002 to 2006. The corresponding incidence of hemorrhagic
      stroke increased from 0.38% for patients diagnosed in 1987-1991 to 0.57% for
      those diagnosed in 2002 to 2006. Covariable-adjusted risk of ischemic stroke was
      significantly reduced (HR 0.65; 0.63-0.68) while risk of hemorrhagic stroke was
      significantly increased (HR 1.19; 1.05-1.36). Compared to the general population,
      total stroke risk decreased more among AF patients. CONCLUSION: We found a
      considerable decrease in risk of ischemic stroke in Sweden in patients without
      prior stroke and with a first hospital diagnosis of AF. There was an increased
      risk of hemorrhagic stroke, but because hemorrhagic stroke represented only a
      small proportion of all strokes, the overall risk of stroke declined.

PMID- 22464489
TI  - Wavelet packet-based independent component analysis for feature extraction from
      motor imagery EEG of complex movements.
AB  - OBJECTIVE: The main goal of this study was to develop a novel spatial filtering
      method for better extracting the feature information underlying the event-related
      de-synchronisation and synchronisation (ERD/ERS) during complex motor imagery of
      lower limb action. METHODS: The algorithm used a wavelet packet-based independent
      component analysis (WPICA) method to extract the ERD/ERS patterns in different
      frequency bands. Time-frequency decomposition in the wavelet packet domain was
      designed to avoid the statistical correlation between different
      electroencephalographic (EEG) rhythms. The subband-specific principal components
      were extracted after independent component analysis and projected back to the
      time-frequency domain of corresponding electrodes for better fitting the varying
      EEG spatial distributions. RESULTS: The present method was tested with the EEG
      data from 10 human subjects performing three complex mental tasks (i.e., imagery
      standing up, imagery left/right foot movement combined with homolateral hand
      movement). A classification rate of about 80% was achieved using the WPICA-based
      technique, which is better than the traditional ICA method with the rate of
      72.30% and the non-spatial filtering condition of 68.34%. CONCLUSIONS: We
      developed a novel spatial filtering method based on WPICA to extract the ERD/ERS
      patterns in different frequency bands. The overall performance of this algorithm
      was better than that of the conventional methods. SIGNIFICANCE: The current
      method promised to provide an effective way for ERD/ERS patterns recognition and
      thus could improve the pattern classification performance of complex mental tasks
      from scalp EEGs.

PMID- 22464490
TI  - Light and transmission electron microscopy of Vibrio campbellii infection in
      gnotobiotic Artemia franciscana and protection offered by a yeast mutant with
      elevated cell wall glucan.
AB  - Luminescent vibrios are amongst the most important pathogens in aquaculture,
      affecting almost all types of cultured organisms. Vibrio campbellii is one of
      these most important pathogens. In this study, the effects of feeding mnn9 yeast
      cell wall mutant and wild type yeast strain were investigated in the digestive
      tract of brine shrimp nauplii, Artemia franciscana, after experimental infection
      with V. campbellii (LMG 21363). Gnotobiotic A. franciscana nauplii were fed daily
      with dead Aeromonas hydrophila LVS3, and with either wild type strain of baker's
      yeast, Saccharomyces cerevisiae, or mutant strain mnn9, of which the cell wall
      contains elevated chitin and glucan and lower mannose levels. After three days of
      feeding, some nauplii were challenged with V. campbellii. Mean survival (%),
      individual length (mm) and total length (mm) at one day and two days after
      challenge were significantly higher in the group fed mnn9 than in the group fed
      wild type yeast (81 +/- 1.50 and 63 +/- 0.49, 1.56 +/- 0.07 and 1.13 +/- 0.02,
      38.21 +/- 3.11 and 21.26 +/- 0.81 respectively for one day and 50 +/- 2.37 and 20
      +/- 1.41, 2.33 +/- 0.01 and 1.24 +/- 0.04, 34.97 +/- 5.56 and 7.45 +/- 1.63 for
      two days after challenge). Histological examination revealed that the luminal
      diameter and enterocyte height of both mid- and hindgut were larger in the mnn9
      fed group. Colonization of the gut lumen by V. campbellii could be observed by
      transmission electron microscopy for the group of nauplii fed with wild type
      yeast. Furthermore, it was observed that V. campbellii caused damage to the gut
      epithelium including shortening and disappearance of the microvilli, destruction
      of the apical cell membrane and cell lysis in the nauplii fed wild type yeast.
      The gut epithelium remained intact in challenged nauplii fed mnn9 yeast. The
      morphological findings of the present study further substantiate previous studies
      reporting a protective effect of this yeast cell wall mutant.

PMID- 22464492
TI  - The vexed question of race-based medical school admissions.

PMID- 22464491
TI  - Genetic and pathogenic characterization of Akabane viruses isolated from cattle
      with encephalomyelitis in Korea.
AB  - A large-scale outbreak of Akabane viral encephalomyelitis in cattle was reported
      in the southern part of Korea in 2010. Fifteen Akabane virus (AKAV) strains were
      isolated from the brain and spinal cord samples by using BHK-21 and/or HmLu-1
      cells. To examine the genetic relationships and characteristics of the isolates,
      nucleotide sequences of the S, M, and L segments of the 15 isolates were
      determined and analyzed. Complete sequence analysis of the 15 AKAV isolates
      showed 99.9-100% amino acid identities, indicating that the 15 isolates
      originated from a single strain. The S and M RNA segments of a representative
      isolate (AKAV-7/SKR/2010) were also compared with the segments of representative
      reference sequences. This AKAV-7/SKR/2010 strain showed the highest identity with
      the Iriki and KM-1/Br/06 strains. Neighbor-joining phylogenetic trees of S and M
      RNA segments were constructed. Four representative AKAV isolates were classified
      into subgroup Ia, which contains the Iriki and KM-1/Br/06 strains recognized to
      cause encephalomyelitis in calves and adult cattle in Japan. Moreover,
      experimental intraperitoneal infection was performed using the AKAV-7/SKR/2010
      and AKAV-17/SKR/2010 strains to assess pathogenesis in suckling mice. The 2
      isolates, genetically related to the Iriki strain, were neurovirulent and caused
      neurological signs in suckling mice. In contrast, the 93FMX strain and the K0505
      strain, related to the OBE-1 strain, were avirulent in mice. The present results
      indicate that these isolates most likely had originated from the Iriki strain and
      are closely related to the Iriki strain both genetically and pathogenically.

PMID- 22464493
TI  - Acute urinary retention as a complication of primary varicella-zoster infection
      of childhood - a second reported case.

PMID- 22464494
TI  - Responding to the evidence for improved treatment for cryptococcal meningitis in
      resource-limited settings.

PMID- 22464495
TI  - Sequel: Chris Barnard and the Hunterian Museum.

PMID- 22464496
TI  - Violence, violence prevention, and safety: a research agenda for South Africa.
AB  - Violence is a serious problem in South Africa with many effects on health
      services; it presents complex research problems and requires interdisciplinary
      collaboration. Two key meta-questions emerge: (i) violence must be understood
      better to develop effective interventions; and (ii) intervention research
      (evaluating interventions, assessing efficacy and effectiveness, how best to
      scale up interventions in resource-poor settings) is necessary. A research agenda
      to address violence is proposed.

PMID- 22464500
TI  - Regulatory crackdown on stem cell therapy: what would the position be in South
      Africa?
AB  - This article attempts to answer the question of whether stem cell therapy falls
      within the current South African regulatory framework, using the Regenexx case in
      the USA as an example. The USA regulator, the Federal Drug Administration (FDA),
      is seeking to regulate the Regenexx autologous stem cell therapy as a 'drug' and
      a 'biological product'. The opposing position taken by the inventors of the
      Regenexx therapy is that re-implantation of one's own body parts can in principle
      not be a 'drug' and that the FDA is exceeding its mandate. In this article
      arguments are presented that the Regenexx therapy would qualify as a 'biological
      medicinal product' in the South African regulatory framework established in terms
      of the Medicines and Related Substances Control Act. As such, the Regenexx
      therapy would be subject to registration with the Medicines Control Council (MCC)
      as a legal precondition for its commercialisation. Furthermore, in order to
      convince the MCC of the safety, efficacy and quality of the Regenexx therapy,
      such therapy must - similar to any other new medicine - first be subjected to
      clinical trials. It is therefore concluded that stem cell therapy is indeed
      comprehensively regulated in South Africa, and that a recent opinion expressed in
      this journal that there exists a 'legislative vacuum' with relation to the
      regulation of stem cell therapy in South Africa is plainly incorrect.

PMID- 22464501
TI  - Does the nose know? Amitraz poisoning and olfaction.
AB  - The initial clinical presentation of amitraz and organophosphate poisoning may be
      similar. Reduced serum pseudocholinesterase supports a diagnosis of
      organophosphate toxicity, but there is no similar laboratory test for amitraz
      poisoning. A 'mothball-like' odour associated with poisoned patients may have
      diagnostic potential. In a blinded controlled trial, 83% (95% confidence
      interval, 63% to 93%) of 23 healthcare workers were able to distinguish between
      the odours of amitraz and organophosphate. Awareness of this simple component of
      bedside examination may allow earlier recognition of this potentially fatal
      poisoning.

PMID- 22464502
TI  - The value of blood culture audits at peripheral hospitals.
AB  - Knowledge of local antibiotic sensitivities is crucial to creating appropriate
      empiric antibiotic guidelines. The new National Health Laboratory Service (NHLS)
      Data Warehouse allows clinicians to access collated spreadsheets of culture
      isolates and antimicrobial susceptibility patterns for their facilities. We used
      this service to study the trends in blood culture (BC) results at GF Jooste
      Hospital from 2005 to 2010. We investigated the BC contamination rate and changes
      in the antibiotic sensitivity profiles of selected organisms, and estimated the
      proportion of infections that were hospital-acquired. Over 3000 BCs were
      performed per year in this period. A very high contamination rate was observed (7
      - 9%) in 2005 - 2007, with a gratifying reduction by 2010. Ceftriaxone resistance
      increased from 16% to 62% in Klebsiella pneumoniae (p<0.0001), and from 33% to
      100% in Enterobacter spp. (p=0.053).

PMID- 22464503
TI  - Heavy metal contamination in a school vegetable garden in Johannesburg.
AB  - BACKGROUND: Feeding schemes based on school garden produce have been proposed as
      an effective solution to food insecurity and hunger among learners in South
      Africa. However, few studies have looked at the potential contamination of school
      food gardens when situated near mine tailing dams. OBJECTIVES: The aim of the
      study was to evaluate the potential heavy metal contamination in a school
      vegetable garden in Johannesburg. METHODS: Twenty soil samples were collected
      from the study school and a comparison school. Surface and deep (+/-10 cm beneath
      the surface) soil samples were analysed using X-ray fluorescence for levels of
      arsenic, chromium, copper, lead and zinc. Thirteen vegetables samples were
      collected from the school garden, and compared with six samples from a national
      retailer and four obtained from a private organic garden. The heavy metal
      concentrations of the vegetable samples were analysed in the laboratories of the
      South African Agricultural Research Council. RESULTS: High levels of arsenic were
      found in the school soil samples, and elevated concentrations of lead and mercury
      in the school vegetables. Calculation of the estimated daily intake for a child
      of 30 kg however, indicated that levels of lead, mercury and arsenic in
      vegetables were within acceptable limits. However, the levels of lead in the
      vegetable samples were high across all three sites. CONCLUSION: Further
      investigation and research should be undertaken to assess the source/s and extent
      of public exposure to heavy metals in vegetables in South Africa.

PMID- 22464504
TI  - Africa's neglected area of human resources for health research - the way forward.
AB  - Building the skills for doing, managing and delivering health research is
      essential for every country's development. Yet, human resources for health
      research (HRHR) are seldom considered in Africa and elsewhere. Africa's health
      research capacity has grown considerably, with potential to increase this growth.
      However, a systemic way of defining, co-ordinating and growing the HRHR needed to
      support health systems development is missing. Reviewing the status of HRHR in
      Africa, we assert that it consists of uncoordinated, small-scale activities,
      primarily driven from outside Africa. We present examples of ongoing HRHR
      capacity building initiatives in Africa. There is no overarching framework,
      strategy or body for African countries to optimise research support and capacity
      in HRHR. A simple model is presented to help countries plan and strategise for a
      comprehensive approach to research capacity strengthening. Everyone engaged with
      global, regional and national research for health enterprises must proactively
      address human resource planning for health research in Africa. Unless this is
      made explicit in global and national agendas, Africa will remain only an
      interested spectator in the decisions, prioritisation, funding allocations,
      conduct and interpretation, and in the institutional, economic and social
      benefits of health research, rather than owning and driving its own health
      research agendas.

PMID- 22464505
TI  - Paediatric liver transplantation in Johannesburg: initial 29 cases and prospects
      for the future.
AB  - BACKGROUND: The Wits Donald Gordon Medical Centre paediatric liver transplant
      programme is the second such unit in sub-Saharan Africa. Initiated in November
      2005, it forms part of the centre's solid organ transplant unit, comprising
      kidney, liver and simultaneous kidney-pancreas arms. Initially established in the
      private sector, we recently received government approval to expand our programme
      into the provincial sector and have performed transplants on several provincial
      sector patients. Current challenges relate to the lack of appropriately trained
      paediatric sub-specialists, specifically critical care practitioners and
      hepatologists. METHODS: Subsequent to institutional approval, a retrospective
      chart analysis of all paediatric liver transplants performed at our facility to
      date was conducted. RESULTS: Defining children as those under 18 years of age, 29
      patients have received a cadaveric liver transplant since 2005, using 16 whole
      livers, 10 reduced-size grafts, and 3 split segments; 13 were transplanted with
      biliary atresia, 3 hyperoxalurea, 3 autosomal recessive polycystic disease, 2
      alpha-1 antitrypsin deficiency, and 2 idiopathic, with the remainder for a wide
      spectrum of other pathologies. Seven patients received combined liver-kidney
      transplants. There were 3 in-hospital mortalities. The remaining 26 patients are
      all long-term survivors. We describe 7 acute surgical morbidities in 6 patients,
      and 8 long-term surgical morbidities. One patient was subsequently re
      transplanted in Cape Town. CONCLUSIONS: Despite a shortage of organs, we have
      overcome a steep learning curve, with results comparable with other early series.
      The current threat to the continued viability of our unit is the lack of
      appropriately trained paediatric hepatologists and intensivists.

PMID- 22464506
TI  - Correlation between a new visual prostate symptom score (VPSS) and uroflowmetry
      parameters in men with lower urinary tract symptoms.
AB  - OBJECTIVE: A visual prostate symptom score (VPSS) compared with the international
      prostate symptom score (IPSS) for evaluation of lower urinary tract symptoms
      (LUTS) can be completed without physician assistance by a significantly larger
      proportion of men with limited education. We aimed to evaluate the correlation of
      the VPSS and IPSS with uroflowmetry parameters. METHODS: Men with LUTS were
      requested to complete the IPSS and VPSS, consisting of pictograms to evaluate
      urinary frequency, nocturia, force of the stream and quality of life. The maximum
      (Qmax) and average urinary flow rate (Qave), voided volume (VV) and post-void
      residual (PVR) urine volumes were measured. Statistical analysis was performed
      using the Mann-Whitney and Spearman's tests. RESULTS: The study included 93 men
      (mean age 64 years, range 33 - 85), with VV >150 ml in 66 (71%) and <150 ml in 27
      (29%) subjects. In the group with VV >150 ml there were significant negative
      correlations between the IPSS and Qmax (r=-0.30, p=0.016), the IPSS and Qave (r=
      0.29, p=0.018), the VPSS and Qmax (r=-0.38, p<0.002) and the VPSS and Qave (r=
      0.37, p<0.003). The VPSS question on the subject's assessment of his urinary
      stream showed a significant negative correlation with the Qmax (r=-0.37, p=0.002)
      and Qave (r=-0.31, p=0.011), but the IPSS question on the subject's urinary
      stream did not correlate significantly with the Qmax or Qave. CONCLUSIONS: The
      VPSS is equivalent to the IPSS in terms of correlation with Qmax and Qave and can
      therefore be used instead of the IPSS to evaluate LUTS in men with limited
      education.

PMID- 22464507
TI  - Door-to-needle time for administration of fibrinolytics in acute myocardial
      infarction in Cape Town.
AB  - OBJECTIVES: To determine the current door-to-needle time for the administration
      of fibrinolytics for acute myocardial infarction (AMI) in emergency centres (ECs)
      at three hospitals in Cape Town, and to compare it with the American Heart
      Association/American College of Cardiology (AHA/ACC) recommendation of 30 minutes
      as a marker of quality of care. METHODS: A retrospective review of case notes
      from January 2008 to July 2010 of all patients receiving thrombolytics for AMI in
      the ECs of three Cape Town hospitals. The total door-to-needle time was
      calculated and patient demographics and presentation, physician qualification,
      clinical symptomology and reasons for delays in thromobolytic administration were
      analysed. RESULTS: A total of 372 patients with acute ST elevation myocardial
      infarction (STEMI) were identified; 161 patients were eligible for the study. The
      median door-to-needle time achieved was 54 minutes (range 13 - 553 mins). A door
      to-needle time of 30 minutes or less was achieved in 33 (20.5%) patients; 51.3%
      of the patients arrived by ambulance; 34% of patients had a pre-hospital 12-lead
      ECG; and 88.8% had typical symptoms of myocardial infarction. Medical officers
      administered thrombolytics to 44.7% of the patients. The predominant infarct
      location on ECG was inferior (55.9%). CONCLUSION: A significant number of
      patients were not thrombolysed within 30 minutes of presentation. The lack of
      senior doctors, difficulty interpreting ECGs, atypical presentations and EC
      system delays prolonged the door-to-needle time in this study.

PMID- 22464508
TI  - Acceptability, feasibility and impact of routine screening to detect undiagnosed
      HIV infection in 17 - 24-month-old children in the western sub-district of Cape
      Town.
AB  - OBJECTIVES: To explore the acceptability and feasibility of routine HIV screening
      in children at primary healthcare clinics and ascertain the prevalence of
      previously undiagnosed HIV infection in 17 - 24 month old children accessing
      curative and routine services. METHODS: A survey was conducted in 4 primary
      health clinics in the western sub-district of Cape Town. Rapid HIV screening of
      17 - 24 month old children was performed for consenting caregiver-child pairs.
      Data on demographics, child health and antenatal history were collected using
      questionnaires. RESULTS: During recruitment, 358 children (72%) were tested for
      HIV infection. Most of the children (95.8%) were accompanied by a parent. The
      prevalence of reported HIV exposure among children was 21% (107/499). Of these, 3
      had previously confirmed HIV infection; 1 was reportedly confirmed by a 6-week
      HIV test, and the other 2 probably contracted the virus via late post-partum
      transmission. The overall transmission rate was 3.5% (3/86) and the confirmed
      proportion of HIV-infected children was 0.8% (3/361). No previously unknown HIV
      infection was detected. CONCLUSIONS: Programmes to prevent mother-to-child
      transmission are effective, but at-risk infants who test negative at 6 weeks
      should be monitored for subsequent seroconversion. Parents of HIV-exposed infants
      are more likely to permit (re)testing of their infants than those whose offspring
      are not at risk. Routine HIV testing of children is feasible and acceptable at
      primary level, but may require additional resources to achieve universal
      coverage. Routine screening at an earlier age may detect previously undiagnosed
      HIV infection.

PMID- 22464509
TI  - Factors affecting career preferences of medical students at the College of
      Medicine, Malawi.
AB  - BACKGROUND: The shortage of doctors in all specialties in Malawi is particularly
      severe in rural areas. Contributory factors are the low number of students
      graduating each year, migration of doctors, and the preference of new graduates
      for practising in urban areas. Attempts to increase the output from Malawi's only
      medical school are insufficient to meet the country's healthcare needs. METHODS:
      We studied the factors influencing career choices of medical undergraduates of
      the College of Medicine in Blantyre, Malawi, who were surveyed by means of a self
      administered questionnaire (N=205) and individual interviews (N=17). RESULTS:
      Most respondents (89.4%) indicated that they intend to specialise abroad,
      predominantly to study in 'better institutions' and to get the 'experience' of a
      different country; 87.0% indicated that they intend to live in Malawi long term.
      Although, in general, the rural lifestyle was unattractive to medical students,
      respondents from rural areas and small towns, and whose parents were 'non
      professionals', were more likely to intend working in rural areas and small
      towns, and to settle in Malawi, than students from urban and professional
      families. CONCLUSIONS: The College of Medicine should consider increasing its
      intake of students with lower socio-economic backgrounds and from rural
      areas/small towns to increase the number of doctors working in rural areas and
      settling in Malawi. However, the Ministry of Health may need a multipronged
      approach to reduce the mismatch between doctors' career expectations and the
      country's healthcare needs.

PMID- 22464510
TI  - William Burchell's medical challenges: a 19th-century natural philosopher in the
      field.
AB  - Two hundred years ago, the naturalist William John Burchell departed from Cape
      Town on extensive travels in South Africa 'solely for the purpose of acquiring
      knowledge'. An intelligent observer who was exceptionally skilled at recording
      his observations in words and pictures, he is remembered for numerous
      contributions to the country as scientist, artist and ethnographer. The medical
      perspective on his travels has yet to receive attention. He identified and
      recorded illnesses of the indigenous peoples with whom he came into contact. He
      also described the medical care he administered to his companions and to himself;
      in doing so, he revealed a profound care for his 'fellow creatures'. His vivid
      and sometimes poignant descriptions remind us of some of the health risks endured
      by early travellers in the country. One of the most riveting is his successful
      care of an assistant whose left hand was severely mutilated when a firearm
      exploded in his hands. Burchell was probably the first person to include the
      materia medica of the Khoi in an essentially European approach to the non
      surgical management of such a serious condition.

PMID- 22464512
TI  - Questioning the findings about canine displacement.

PMID- 22464514
TI  - The best continuing education.

PMID- 22464515
TI  - Infraoccluded deciduous molars.

PMID- 22464516
TI  - Questioning treatment strategies in hyperdivergent patients.

PMID- 22464518
TI  - Ethics in orthodontics. Quest for the best.

PMID- 22464520
TI  - Cone-beam computed tomography is the imaging technique of choice for
      comprehensive orthodontic assessment.

PMID- 22464521
TI  - Cone-beam computed tomography is not the imaging technique of choice for
      comprehensive orthodontic assessment.

PMID- 22464522
TI  - Bone damage associated with orthodontic placement of miniscrew implants in an
      animal model.
AB  - INTRODUCTION: The purposes of this study were to quantify bone damage associated
      with insertion of 2 types of miniscrew implants and to relate the amount of bone
      damage to monocortical plate thickness. METHODS: Nondrilling (n = 28) and self
      drilling (n = 28) miniscrew implants (6 * 1.6 mm, Dentaurum, Newtown, Pa), and
      pilot holes (n = 26) were placed bilaterally in the maxillae and the mandibles of
      5 adult dogs immediately after death. Bone blocks were cut, bulk stained with 1%
      basic fuchsin, embedded in methyl methacrylate, sectioned, and mounted.
      Monocortical plate thickness was measured adjacent to the miniscrew implant
      insertion site. Damage amounts were quantified at distances of 0 to 0.5 mm
      (adjacent region) and 0.5 to 1 mm (distant region) from the bone-implant
      interface. Total fractional damaged area (%), fractional microcracked area (%),
      and fractional diffuse damaged area (%) were quantified by using standard
      histomorphometric methods. RESULTS: The mean monocortical plate thickness of the
      specimens from the mandible (2.2 mm) was significantly (P <0.001) greater than
      that of the maxillary specimens (0.9 mm). In the mandible, the 3 damage
      parameters were greater with self-drilling miniscrew implants than with
      nondrilling miniscrew implants; however, there were no differences in the damage
      parameters in the maxilla. CONCLUSIONS: Bone damage accumulation is related to
      the type of miniscrew implant and the thickness of the bone.

PMID- 22464523
TI  - Real-time cell analysis of the cytotoxicity of orthodontic mini-implants on human
      gingival fibroblasts and mouse osteoblasts.
AB  - INTRODUCTION: The aim of this study was to evaluate the cytotoxic effects of
      orthodontic mini-implants on gingival fibroblasts and osteoblasts. METHODS: The
      orthodontic mini-implants used in this study were Orthodontic Mini Implant
      (Leone, Florence, Italy), MTN (MTN, Istanbul, Turkey), AbsoAnchor (Dentos, Daegu,
      South Korea), IMTEC Ortho (3M Unitek, IMTEC, Ardmore, Okla), VectorTAS (Ormco,
      Glendora, Calif). The materials were incubated in Dulbecco's modified eagle's
      culture medium for 72 hours according to ISO 10993-5 standards (surface area-to
      volume ratio of the specimen to cell-culture medium, 3 cm(2)/mL). A real-time
      cell analyzer (xCELLigence, Roche Applied Science, Mannheim, Germany; ACEA
      Biosciences, San Diego, Calif) was used to evaluate cell survival. After seeding
      200 MUL of the cell suspensions into the wells of the E-plate 96, gingival
      fibroblasts were treated with bioactive components released by the metallic
      materials and monitored every 15 minutes for 190 hours. For the proliferation
      experiments, the statistical analyses used were 1-way analysis of variance and
      Tukey-Kramer multiple comparisons tests. RESULTS: There was no significant
      differences between the human gingival fibroblast cell indexes of the control and
      study groups (P >0.05). When evaluated at 27 and 96 hours, only the VectorTAS
      mini-implants showed statistically significant decreases in the M3T3 cell index
      (P <0.001) compared with the control group. No significant differences were found
      among the control and all study groups (P >0.05). Furthermore, the Leone and MTN
      mini-implants showed statistically significant decreases (P <0.001) at 190 hours.
      Also, the VectorTAS mini-implants demonstrated a significant decline (P <0.05) at
      the same time in the M3T3 cell index. CONCLUSIONS: These findings provide
      fundamental knowledge and new insights for future design and development of new
      biocompatible titanium alloys for orthodontic mini-implants and temporary
      anchorage devices.

PMID- 22464524
TI  - Apical root resorption of incisors after orthodontic treatment of impacted
      maxillary canines: a radiographic study.
AB  - INTRODUCTION: The purpose of the study was to evaluate impacted maxillary canines
      as risk factor for orthodontic apical root resorption. METHODS: The sample
      comprised 66 patients treated with fixed appliances. Thirty-two patients with a
      unilateral impacted maxillary canine, which was distanced from the roots of the
      incisors at a preliminary phase of treatment before bonding, formed the impaction
      group, and 34 patients without impactions served as the controls. Root shortening
      was calculated by using pretreatment and posttreatment intraoral radiographs.
      Inclination of the eruption path of the impacted canine relative to the midline,
      axis of the lateral incisor, and nasal line, root development, and the medial and
      vertical positions of the impacted tooth were recorded on orthopantomograms and
      lateral cephalometric films. The follicle/tooth ratio was evaluated by using
      periapical radiographs. RESULTS: No significant difference in apical resorption
      of the maxillary incisors was detected between the impaction and control groups,
      or between the incisors of the impacted and contralateral sides in the same
      subject. Likewise, no difference in the severity of root resorption was found
      between the incisors of impacted side alone and the incisors of the control
      group. Mesial and vertical inclinations of the impacted canines were negatively
      related to a lateral incisor's root resorption. No correlations were found
      between resorption and medial or vertical position of the crown of the canine.
      The follicle/tooth ratio was significantly related to the mesial inclination of
      the impacted canine, but not to root resorption. CONCLUSIONS: An impacted
      maxillary canine, after being distanced from the incisor roots, does not seem to
      be a risk factor for apical root resorption during orthodontic treatment.

PMID- 22464525
TI  - Dosimetry of a cone-beam computed tomography machine compared with a digital x
      ray machine in orthodontic imaging.
AB  - INTRODUCTION: Cone-beam computed tomography (CBCT) has become a routine imaging
      modality for many orthodontic clinics. However, questions remain about the amount
      of radiation patients are exposed to during the scans. This study determined the
      amounts of radiation potentially absorbed by a patient during orthodontic imaging
      with a CBCT machine with various scan settings compared with a conventional 2
      dimensional digital x-ray machine. METHODS: The radiation exposures delivered by
      a next generation i-CAT CBCT machine (Imaging Sciences International, Hatfield,
      Pa) at various scan settings and orthopantomograph OP100/OC100 digital x-ray
      machine (Instrumentarium Dental, Tuusula, Finland) during panoramic and
      cephalometric radiography were recorded using thermoluminescent dosimeters placed
      inside a head and neck phantom. The manufacturer-recommended settings for an
      average adult male were used for both types of machines. Effective doses were
      calculated using the tissue-weighting factors recommended by the 2007
      International Commission on Radiological Protection. RESULTS: The effective doses
      at various voxel sizes and field of view settings ranged from 64.7 to 69.2 MUSv
      for standard resolution CBCT scans (scan time 8.9 s) and 127.3 to 131.3 MUSv for
      high resolution full field of view scans (scan time 17.8 s), and measured 134.2
      MUSv for a high-resolution landscape scan with a voxel size as would be used for
      SureSmile (OraMetrix, Richardson, Tex) therapy (scan time 26.9 s). The effective
      doses for digital panoramic and lateral cephalometric radiographs measured 21.5
      and 4.5 MUSv, respectively. CONCLUSIONS: CBCT, although providing additional
      diagnostic and therapeutic benefits, also exposes patients to higher levels of
      radiation than conventional digital radiography.

PMID- 22464526
TI  - Effect of a low-level laser on bone regeneration after rapid maxillary expansion.
AB  - INTRODUCTION: In this study, we evaluated the effects of a low-level laser on
      bone regeneration in rapid maxillary expansion procedures. METHODS: Twenty-seven
      children, aged 8 to 12 years, took part in the experiment, with a mean age of
      10.2 years, divided into 2 groups: the laser group (n = 14), in which rapid
      maxillary expansion was performed in conjunction with laser use, and the no-laser
      group (n = 13), with rapid maxillary expansion only. The activation protocol of
      the expansion screw was 1 full turn on the first day and a half turn daily until
      achieving overcorrection. The laser type used was a laser diode (TWIN Laser;
      MMOptics, Sao Carlos, Brazil), according to the following protocol: 780 nm
      wavelength, 40 mW power, and 10 J/cm(2) density at 10 points located around the
      midpalatal suture. The application stages were 1 (days 1-5 of activation), 2 (at
      screw locking, on 3 consecutive days), 3, 4, and 5 (7, 14, and 21 days after
      stage 2). Occlusal radiographs of the maxilla were taken with the aid of an
      aluminum scale ruler as a densitometry reference at different times: T1
      (initial), T2 (day of locking), T3 (3-5 days after T2), T4 (30 days after T3),
      and T5 (60 days after T4). The radiographs were digitized and submitted to
      imaging software (Image Tool; UTHSCSA, San Antonio, Tex) to measure the optic
      density of the previously selected areas. To perform the statistical test,
      analysis of covariance was used, with the time for the evaluated stage as the
      covariable. In all tests, a significance level of 5% (P <0.05) was adopted.
      RESULTS: From the evaluation of bone density, the results showed that the laser
      improved the opening of the midpalatal suture and accelerated the bone
      regeneration process. CONCLUSIONS: The low-level laser, associated with rapid
      maxillary expansion, provided efficient opening of the midpalatal suture and
      influenced the bone regeneration process of the suture, accelerating healing.

PMID- 22464527
TI  - Efficacy of identifying maxillofacial lesions in cone-beam computed tomographs by
      orthodontists and orthodontic residents with third-party software.
AB  - INTRODUCTION: The purpose of this study was to determine the ability of
      orthodontists and orthodontic residents to identify nonorthodontic incidental
      findings and false positives in cone-beam computed tomography scans. METHODS: Two
      groups of 10 cone-beam computed tomography scans containing equal numbers of
      scans with no, 1, or several abnormal nonorthodontic lesions were selected from a
      database. Eight orthodontists and 8 orthodontic residents screened the 2 groups
      of scans before and after a basic cone-beam computed tomography training course.
      The paired t test was used for statistical analyses. RESULTS: In the initial
      screening, the orthodontists and residents correctly identified 41.1% of the
      lesions. This lesion-detection rate improved significantly to a mean of 56.7%
      after the training course (P <0.0005). In parallel with these findings, the mean
      percentage of correctly identified extragnathic lesions improved significantly,
      from 22% to 48% (P <0.0005), and correctly identified temporomandibular joint
      lesions improved from 20% to 55% (P = 0.01) after the training. In contrast, the
      rate of correctly identified dentomaxillofacial lesions remained largely
      unchanged before and after the training. Both groups of evaluators had
      approximately 5 false positives per 10 scans before training and demonstrated
      significant decreases in false positives after training. CONCLUSIONS: Relative to
      known error rates in medical radiology, both groups of evaluators had high error
      rates for missed lesions and false positives before and after training. Given
      these findings and since the most frequent cause of medical radiology malpractice
      litigation is due to missed lesions, it is recommended that an appropriately
      trained radiologist should be involved in reading and interpreting cone-beam
      computed tomography scans.

PMID- 22464528
TI  - Influence of optical properties of esthetic brackets (color, translucence, and
      fluorescence) on visual perception.
AB  - INTRODUCTION: The aims of this study were to evaluate the optical properties of
      esthetic brackets and determine their influence on visual perception. METHODS:
      Eighty esthetic brackets of 16 commercial brands were tested. The color and
      translucency of the brackets, as well as the color of the maxillary central
      incisors of 40 subjects, were measured with a spectrophotometer. The fluorescence
      of the brackets was determined by duly calibrated appraisers. The color
      differences between the brands of brackets and the teeth were calculated. Data
      were analyzed by using 1-way analysis of variance; the Scheffe multiple
      comparison test was used to establish the difference between brands of brackets,
      (alpha = 0.05). RESULTS: The color parameters L * a * b * of nontranslucent
      brackets ranged from 49.4 to 86.0, -1.6 to 3.0, and 1.9 to 14.6, respectively.
      The direct transmission of light ranged from 0.0% to 38.8% transmittance. No
      bracket showed fluorescence. The color and translucency, as well as the color
      difference, of the brackets were influenced by brand (P <0.01). CONCLUSIONS: The
      optical properties of esthetic brackets have a direct influence on visual
      perception; translucent brackets and the nontranslucent InVu (TP Orthodontics,
      LaPorte, Ind) brackets were less visually perceptible.

PMID- 22464529
TI  - Finite element analysis of miniscrew implants used for orthodontic anchorage.
AB  - INTRODUCTION: The miniscrew has been developed and effectively used as
      orthodontic anchorage, but current studies of its usage are insufficient to
      provide information about the underlying mechanical mechanisms. The aim of this
      study was to investigate the roles of bone quality, loading conditions, screw
      effects, and implanted depth on the biomechanics of an orthodontic miniscrew
      system by using finite element analysis. METHODS: A 3-dimensional model with a
      bone block integrated with a miniscrew was constructed to simulate various cortex
      thicknesses, cancellous bone densities, force magnitudes and directions, screw
      diameters and lengths, and implanted depths of miniscrews. RESULTS: Both stress
      and displacement increased with decreasing cortex thickness, whereas cancellous
      bone density played a minor role in the mechanical response. These 2 indexes were
      linearly proportional to the force magnitude and produced the highest values when
      the force was perpendicular to the long axis of the miniscrew. A wider screw
      provided superior mechanical advantages. The exposed length of the miniscrew was
      the real factor affecting mechanical performance. CONCLUSIONS: The screw diameter
      was the dominant factor for minscrew mechanical responses. Both bone stress and
      screw displacement decreased with increasing screw diameter and cortex thickness,
      and decreasing exposed length of the screw, force magnitude, and oblique loading
      direction.

PMID- 22464530
TI  - Relapse of orthodontically corrected deepbites in accordance with growth pattern.
AB  - INTRODUCTION: A common orthodontic problem is a deep overbite malocclusion.
      Because of its high relapse tendency, it is also one of the most challenging
      problems to treat. To minimize relapse, the morphologic characteristics of
      patients need to be considered. The aim of this study was to compare deepbite
      relapse in 3 groups of patients categorized by vertical growth type. METHODS: The
      total sample included 60 patients treated at the University of Washington in
      Seattle, all with initial overbites greater than 50%. Data were collected from
      casts and cephalometric radiographs at 3 time points: pretreatment,
      posttreatment, and 10 years postretention. A mixed-effects model (analysis of
      variance) and post-hoc t tests were used for the statistical evaluations.
      RESULTS: The high-angle subjects showed the least deepbite relapse (0.1 +/- 1.1
      mm), whereas the low-angle (1.2 +/- 0.9 mm) and the normal-angle (1.4 +/- 1.3 mm)
      subjects had statistically significant relapses P <0.001. This overbite relapse
      might be partially due to changes in the mandibular and interincisal angles,
      which were also observed in these 2 groups. CONCLUSIONS: High-angle subjects tend
      to relapse less in overbite than do low-angle and normal-angle subjects in the
      long term.

PMID- 22464531
TI  - En-masse retraction dependent on a temporary skeletal anchorage device without
      posterior bonding or banding in an adult with severe bidentoalveolar protrusion:
      seven years posttreatment.
AB  - This report describes a novel concept of en-masse retraction with temporary
      skeletal anchorage devices in place of posterior bonding or banding. The patient
      was a Korean woman, aged 24 years 4 months, with a Class II Division 1
      malocclusion with severe mandibular anterior crowding. Both molars showed
      decalcification of the cervical areas. Partial osseointegration-based C-implants
      and C-tube plates were placed bilaterally between the maxillary second premolars
      and the first molars and in the posterior mandible. These temporary skeletal
      anchorage devices were used as independent appliances for full retraction of the
      maxillary and mandibular anterior teeth 3-dimensionally without the assistance of
      posterior bonded appliances. The posterior occlusion was not changed during
      treatment, and Class I occlusal relationships with optimal overjet and overbite
      were achieved. The 7-year posttreatment records showed a stable result.

PMID- 22464532
TI  - Treatment of ankylosed maxillary central incisors by segmental osteotomy with
      autogenous bone graft.
AB  - This case report describes the treatment of a 16-year-old girl with ankylosed
      maxillary central incisors that were noticeably infraoccluded and labially
      displaced. We performed a segmental osteotomy with an autogenous bone graft in a
      single-stage surgery to align and level the ankylosed teeth. The dento-osseous
      segment was successfully repositioned with satisfactory periodontal results.

PMID- 22464534
TI  - Social media basics for orthodontists.
AB  - One of the most common buzz words in today's online world is "social media." This
      article defines social media, explains why it is important to practicing
      orthodontists, and provides information about how doctors can incorporate it into
      their practices. Five of the most useful social media tools are described in
      detail, outlining the strengths, weaknesses, opportunities, and risks inherent in
      each.

PMID- 22464533
TI  - Modified bonding technique for a standardized and effective indirect bonding
      procedure.
AB  - This article describes a modified technique for indirect bonding. Crucial
      variables that influence the procedure are analyzed and discussed to help the
      clincian use the indirect bonding techinique routinely.

PMID- 22464535
TI  - Litigation and legislation. Materiality and materials.

PMID- 22464536
TI  - Sample calculations for comparison of 2 means.

PMID- 22464537
TI  - Eight-year stability of a severe skeletal anterior open bite with a
      hyperdivergent growth pattern treated with an edgewise appliance and chin cup
      therapy.
AB  - An adolescent boy with an Angle Class II Division 1 malocclusion had a
      hyperdivergent growth pattern with an excessive lower facial height and an
      anterior open bite. Combined orthodontic and surgical treatment should be
      considered for patients with a skeletal anterior open-bite malocclusion. For
      patients who do not want surgery, however, a 0.022 * 0.028-in nontorqued,
      nonangulated fixed appliance with a chincup as adjunct therapy is an alternative
      that can have excellent results. The final outcome of this treatment were great
      improvements in function, esthetics, and posttreatment stability after 8 years.

PMID- 22464538
TI  - [Glucocentricity or adipocentricity: The unceasing quest for El Dorado].

PMID- 22464539
TI  - Overweight and obesity in young people according to national and international
      standards.

PMID- 22464540
TI  - Cinacalcet for management of hypercalcemia secondary to calcium-sensing receptor
      mutation.

PMID- 22464541
TI  - Effect of temperature on the sorption of europium on alumina: microcalorimetry
      and batch experiments.
AB  - The determination of enthalpies of reactions (aqueous and surface complexation)
      is used in this work to model the temperature effect on the adsorption processes.
      Microcalorimetry experiments were carried out to determine the enthalpy of
      adsorption of europium on gamma-alumina at 25  degrees C. The stability constants
      at 50  degrees C were then calculated with the van't Hoff equation, and a 2-pK
      approach was used to model the adsorptive behavior of Eu on alumina at 50 
      degrees C, as a function of pH. The results have shown that the adsorption of
      Eu(3+) on the alumina surface is weakly endothermic. In the experimental
      conditions considered in the present study, the temperature has only a small
      effect on the adsorption reaction.

PMID- 22464542
TI  - Influence of ceria modification on the properties of TiO2-ZrO2 supported V2O5
      catalysts for selective catalytic reduction of NO by NH3.
AB  - TiO(2)-ZrO(2) (hereafter denoted as Ti-Zr) supported V(2)O(5) catalysts with
      different loadings of CeO(2) were synthesized, and their physicochemical
      properties were characterized by Brunauer-Emmett-Teller (BET), X-ray diffraction
      (XRD), in situ Fourier transform infrared spectroscopy (in situ FT-IR) and
      temperature-programmed reduction (TPR). Their catalytic activities toward the
      NO(x) reduction reaction with NH(3) were tested. We found that with the addition
      of CeO(2), more NO was removed in a wide temperature range of 220-500  degrees C.
      As the CeO(2) content was increased from 10% to 20% (i.e., the molar ratio of Ce
      to Ti-Zr), NO conversion increased significantly; after that, increasing CeO(2)
      content, however, decreased NO conversion. In particular, the addition of CeO(2)
      to V(2)O(5)/Ti-Zr suppressed the coke deposition and rendered a stable and high
      catalytic activity. The characterization results indicated that: (1) the
      deposited vanadium and cerium oxides were highly dispersed over the Ti-Zr
      support, and in addition to ZrV(2)O(7), a common binary compound observed in
      V(2)O(5)/Ti-Zr, CeVO(4) and Ce(3)ZrO(8) was formed upon increasing CeO(2)
      content; (2) the introduction of CeO(2) to V(2)O(5)/Ti-Zr sample promoted the
      redox ability of the resulting catalysts; and (3) the Ce-containing catalysts
      possessed the greater amount of surface acidic and active intermediate.

PMID- 22464543
TI  - Robotic versus laparoscopic partial nephrectomy for complex tumors: comparison of
      perioperative outcomes.
AB  - BACKGROUND: Recent studies showed that robotic partial nephrectomy (RPN) offered
      outcomes at least comparable to those of laparoscopic partial nephrectomy (LPN).
      LPN can be particularly challenging for more complex tumors. OBJECTIVE: To
      compare the perioperative outcomes of patients undergoing LPN or RPN for a single
      renal mass of moderate or high complexity. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective analysis was performed for 381 consecutive patients who underwent
      either LPN (n = 182) or RPN (n = 199) between 2005 and 2011 for a complex renal
      mass (RENAL score >= 7). Perioperative outcomes were compared. Predictors of
      postoperative renal function were assessed using multivariable linear regression
      analysis. INTERVENTION: LPN or RPN. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Perioperative outcomes were compared. Predictors of postoperative renal
      function were assessed using multivariable linear regression analysis. RESULTS
      AND LIMITATIONS: There was no significant difference between the two groups with
      respect to patient age, gender, side, American Society of Anesthesiologists
      score, Charlson comorbidity index (CCI), or tumor size. Patients undergoing LPN
      had a slightly lower body mass index (29.2 kg/m(2) compared with 30.7 kg/m(2), p
      = 0.02) and preoperative estimated glomerular filtration rate (eGFR) (81.1
      compared with 86.0 ml/min per 1.73 m(2), p = 0.02). LPN was associated with an
      increased rate of conversion to radical nephrectomy (RN) (11.5% compared with 1%,
      p<0.001) and a higher decrease in percentage of eGFR (-16.0% compared with 
      12.6%, p = 0.03). There were no significant differences with respect to warm
      ischemia time (WIT), estimated blood loss, transfusion rate, or postoperative
      complications. WIT, preoperative eGFR, and CCI were found to be predictors of
      postoperative eGFR in multivariable analysis. No difference in perioperative
      outcomes was found between moderate and high RENAL score subgroups. The
      retrospective study design was the main limitation of this study. CONCLUSIONS:
      RPN provides functional outcomes comparable to those of LPN for moderate- to high
      complexity tumors, but with a significantly lower risk of conversion to RN. This
      situation is likely because of the technical advantages offered by the
      articulated robotic instruments. A prospective randomized study is needed to
      confirm these findings.

PMID- 22464545
TI  - [Recent findings in the epidemiology, diagnosis and treatment of lower-limb
      superficial-vein thrombosis].

PMID- 22464546
TI  - [Lesions of the corpus callosum].

PMID- 22464547
TI  - An evaluation of the IDEEATM activity monitor for estimating energy expenditure.
AB  - Objective estimates of activity patterns and energy expenditure (EE) are
      important for the measurement of energy balance. The Intelligent Device for
      Energy Expenditure and Activity (IDEEA) can estimate EE from the thirty-five
      postures and activities it can identify and record. The present study evaluated
      the IDEEA system's estimation of EE using whole-body indirect calorimetry over 24
      h, and in free-living subjects using doubly-labelled water (DLW) over 14 d. EE
      was calculated from the IDEEA data using calibration values for RMR and EE while
      sitting and standing, both as estimated by the IDEEA system (IDEEA(est)) and
      measured by indirect calorimetry (IDEEA(meas)). Subjects were seven females and
      seven males, mean age 38.1 and 39.7 years, mean BMI 25.2 and 26.2 kg/m2,
      respectively. The IDEEA(est) method produced a similar estimate of EE to the
      calorimeter (10.8 and 10.8 MJ, NS), while the IDEEA(meas) method underestimated
      EE (9.9 MJ, P < 0.001). After removing data from static cycling, which the IDEEA
      was unable to identify as an activity, both the IDEEA(est) and IDEEA(meas)
      methods overestimated EE compared to the calorimeter (9.9 MJ, P < 0.001; 9.1 MJ,
      P < 0.05 and 8.6 MJ, respectively). Similarly, the IDEEA system overestimated EE
      compared to DLW over 14 d; 12.7 MJ/d (P < 0.01), 11.5 MJ/d (P < 0.01) and 9.5
      MJ/d for the IDEEA(est), IDEEA(meas) and DLW, respectively. The IDEEA system
      overestimated EE both in the controlled laboratory and free-living environments.
      Using measured EE values for RMR, sitting and standing reduced, but did not
      eliminate, the error in estimated EE.

PMID- 22464548
TI  - HDAC6 as a target for antileukemic drugs in acute myeloid leukemia.
AB  - Inhibition of histone deacetylases (HDACs) by drugs such as vorinostat or
      depsipeptide has become treatment strategy under study in acute myeloid leukemia.
      Most preclinically and clinically investigated HDACi target classes I, II and IV,
      but only few are selective in inhibiting specific HDACs. Here we analyzed the in
      vitro antileukemic activity of three novel hydroxamate derivatives, the pan-HDAC
      inhibitors ST13, ST34 and the known HDAC6 inhibitor ST80, treating leukemia cell
      lines HL60, Kasumi-1, NB-4, THP-1, K562, U937, Jurkat as well as primary AML
      blasts. In cell lines all three compounds exerted a strong growth-inhibitory
      effect at low micromolar concentrations. ST13 increased acetylation of H3, H4 and
      alpha-tubulin, while ST34 preferentially acetylated histones H3 and H4.
      Interestingly, ST80 preferentially induced alpha-tubulin acetylation at low
      micromolar doses, confirming a selective inhibition of HDAC6 by ST80 in leukemic
      cells. These observations were also confirmed in primary AML blasts cultured ex
      vivo. Growth-inhibition by ST80 was independent of pre-treatment HDAC6 protein
      expression and in contrast to ST13 and ST34, ST80 did not result in induction of
      p21/WAF. Immunofluorescence imaging confirmed that ST80 treatment both increased
      the abundance and resulted in unilateral local accumulation of acetylated alpha
      tubulin. In conclusion, the three novel HDACi show potent antileukemic activity
      in myeloid cell lines and primary AML blasts at low micromolar concentrations.
      Preferential acetylation of alpha-tubulin implies that ST80 might exert its
      antileukemic effect not through histone reacetylation but rather through
      inhibition of HDAC6.

PMID- 22464549
TI  - Role of peroxisome proliferator-activated receptor beta agonist on angiogenesis
      in hindlimb ischemic diabetic rats.
AB  - INTRODUCTION: Studies indicated that PPARbeta agonists play a role in modulation
      of angiogenesis. In this study, we evaluated the effect of specific PPARbeta
      agonist, GW0742, on angiogenesis and serum vascular endothelial growth factor
      (VEGF), VEGF receptor-2 (VEGFR-2), and nitrite concentrations in hindlimb
      ischemia in normal and diabetic rats. METHODS: Hindlimb ischemic rats were
      divided into four groups: control, diabetic, control, and diabetic treated with
      GW0742 (n=7 each). Diabetes was induced by injection of streptozotocin (55mg/kg,
      ip). GW0742 was injected 1day after surgery (1mg/kg, sc). After 21days, blood
      samples were taken, and gastrocnemius muscles were harvested for
      immunohistochemistry. RESULTS: GW0742 significantly increased serum nitrite and
      VEGFR-2 concentrations and VEGF-to-VEGFR-2 ratio in control and diabetic rats.
      Capillary density was lower in diabetic animals compared to the control, and
      GW0742 significantly restored the capillary density in the control and diabetic
      hindlimb ischemic rats. CONCLUSION: PPARbeta agonists restore skeletal muscle
      angiogenesis and can be considered for prevention and/or treatment of peripheral
      vascular complications in diabetic subjects.

PMID- 22464550
TI  - Mixture of hyaluronic acid, chondroitin 6 sulphate and dermatan sulphate used to
      completely regenerate bone in rat critical size defect model.
AB  - Skeletal bone losses are mainly filled with autologous graft or artificial
      materials. Osteoblasts are essential to maintain bone homeostasis and bone repair
      through a matrix synthesis. We have previously demonstrated that adherence and
      regenerative matrix composition are fundamental to bone healing, even in critical
      situations. In this work the critical size defect technique was used to evaluate
      the systemic activity on bone regeneration of a novel mixture of extracellular
      polysaccharides. A 5mm diameter hole was made in each parietal bone of male
      Wistar rats. The right parietal bone hole was filled with a mixture of hyaluronic
      acid, chondroitin 6 sulphate, and dermatan sulphate mixed with 2.5% NaCl
      solution, while the left hole was left free of material and untreated and
      considered as control. Twenty-one days after surgery, the holes and surrounding
      tissues were examined visually, using X-rays, and by histological staining. Using
      the matrix substitute, bone healing was almost complete after 21 days in the
      treated hole and always complete in the control side due to some systemic effect.
      Neovascularization was also observed along with organized trabecular bone on both
      sides. No abnormal bone growth or connective tissue abnormalities were noted. At
      the end of the experiment, 95.1% (+/- 3.2) bone healing (n=20) was observed on
      the treated side; conversely, healing bone and histological structure were better
      on the control side.

PMID- 22464551
TI  - Non-alcoholic fatty liver disease in children now: lifestyle changes and
      pharmacologic treatments.
AB  - Over the past decade, non-alcoholic fatty liver disease (NAFLD) has become one of
      most common chronic liver diseases in children. A greater understanding about the
      risk factors and molecular pathogenesis of NAFLD suggests that lifestyle
      interventions aiming to decrease obesity/body mass index and metabolic
      derangement are the first line of treatments adopted in children affected by this
      disease. However, because these therapeutic options are often at the beginning
      misjudged by the patients and their parents, the use of pharmacologic agents may
      help to protect the liver and other organs from further irreversible tissue
      damage. Pharmacologic therapies against one or more specific factors and/or
      molecules involved in the development of NAFLD (i.e., insulin resistance, free
      fatty acid lipid toxicity, and oxidative stress) also might slow the progression
      of this increasingly prevalent pediatric disorder. On this basis, insulin
      sensitizers, antioxidants, cytoprotective agents, and dietary supplementations
      have been evaluated in pediatric clinical trials. In this review, we discuss the
      efficacy of the dietary approaches, possibly coupled with regular exercise, on
      decreasing the metabolic and histologic damage in pediatric NAFLD. We also
      emphasize several advantages of the pharmacologic treatments adopted or adoptable
      in combination with lifestyle interventions in children with NAFLD.

PMID- 22464552
TI  - Description and prediction of resting metabolic rate after stroke and traumatic
      brain injury.
AB  - OBJECTIVE: To compare the effect of stroke on the metabolic rate compared with
      the effect of traumatic brain injury and to determine whether the metabolic rate
      is predictable in both types of brain injury. METHODS: Indirect calorimetry was
      conducted prospectively in mechanically ventilated patients within the first 6 d
      of admission to a critical care unit owing to ischemic stroke, hemorrhagic
      stroke, isolated traumatic brain injury, or traumatic brain injury with
      collateral injuries. Clinical data were collected simultaneously and a predicted
      value of the resting metabolic rate was calculated using the Penn State equation
      (using body size, body temperature, and minute ventilation). RESULTS: One hundred
      thirty patients were measured. Ischemic stroke showed a lower incidence of fever,
      a lower body temperature, and a lower resting metabolic rate than the other
      groups; whereas in hemorrhagic stroke, these variables were similar to the trauma
      groups. Sedation decreased the resting metabolic rate, but this effect seemed
      particular to the trauma patients. The Penn State equation predicted the resting
      metabolic rate accurately 72% of the time, and when its component variables of
      body temperature and minute ventilation were controlled in an analysis of
      variance, all the differences among the brain injury and sedation groups were
      eliminated. CONCLUSION: Stroke is a hypermetabolic event most of the time. Body
      size, temperature, and minute ventilation explain most of the variation in the
      resting metabolic rate after traumatic and non-traumatic brain injuries. The Penn
      State equation therefore predicts the resting metabolic rate in brain-injured
      patients no matter the mechanism of injury.

PMID- 22464553
TI  - Redo autograft operations after the Ross procedure.
AB  - BACKGROUND: Autograft dilatation after the Ross procedure is the most common
      cause of late autograft failure. We looked at results after reoperation for
      autograft dysfunction using autograft sparing and composite root replacement
      techniques. METHODS: Data were abstracted from our prospectively collected Ross
      registry for 160 consecutive patients who underwent a Ross procedure by a single
      surgeon between 1994 and 2008. Follow-up records were obtained, and the last
      echocardiographic report after reoperation was analyzed. RESULTS: Autograft
      reoperation was necessary in 17 patients, at a median interval of 6.9 years after
      the original procedure. Indications for reoperation were insufficiency with
      autograft dilatation in 16 patients, and without dilatation in 1 patient.
      Surgical procedures used at reoperation included autograft reimplantation in 6
      patients (35.3%), autograft remodeling procedure in 1 patient (5.9%), composite
      root replacement with mechanical valved conduit in 5 patients (29.4%), composite
      root replacement with biologic valved conduit in 3 patients (17.6%), and
      mechanical aortic valve replacement in 2 patients (11.8%). At a median follow-up
      of 5.0 years after reoperation, freedom from greater than 2+ aortic insufficiency
      was 100% (17 of 17 patients) in both reimplantation and replacement groups. There
      was 1 death after reoperation (at >14 years) related to complications from
      systemic lupus erythematosus. There have been no strokes after autograft
      reimplantation. CONCLUSIONS: Autograft valve reimplantation and composite aortic
      root replacement are effective treatments for aortic root dilatation and aortic
      insufficiency after the Ross procedure. Echocardiographic follow-up demonstrates
      reasonable short-term function after autograft preservation procedures.

PMID- 22464554
TI  - Histologic findings in biopsies/resection specimens from the small intestine with
      special emphasis on celiac disease: experience from a developing country in South
      Asia.
AB  - Biopsies from the small intestine especially the duodenum are now being performed
      much more frequently than in the past. The most frequent reason for performing
      duodenal biopsies is to evaluate for malabsorption. In the last few years,
      increased awareness has resulted in more biopsies sent for evaluation of
      malabsorption, especially celiac disease (CD). In the duodenum, features of
      malabsorption (increased intraepithelial lymphocytes, villous shortening, and
      atrophy) were the most common histologic finding seen in 63.4% of cases. Serum
      tTG levels were available for correlation in 52.8% of cases. In patients with
      confirmed CD, 53.4% were MARSH IIIb, and 29.5% were MARSH IIIc. The most common
      specific condition diagnosed in the ileum was tuberculosis (35.6%), and 80.8%
      with ileal tuberculosis were women. Our findings, although preliminary, indicate
      that CD is not so rare in Pakistan. These are the first findings from Pakistan on
      this subject, and larger studies are required to determine the true frequency and
      impact of CD in Pakistan.

PMID- 22464555
TI  - Triprotic site-specific acid-base equilibria and related properties of
      fluoroquinolone antibacterials.
AB  - The complete macro- and microequilibrium analyses of six fluoroquinolone drugs -
      ciprofloxacin, enrofloxacin, norfloxacin, pefloxacin, ofloxacin and moxifloxacin 
      are presented. Previous controversial literature data are straightened up, the
      protonation centers are unambiguously identified, and the protonation macro- and
      microconstant values are reported. The macroconstants were determined by (1)H NMR
      pH titrations while the microconstants were determined by a multi-modal
      spectroscopic-deductive methodology, in which methyl ester derivatives were
      synthesized and their NMR-pH titration data contributed to the evaluation of all
      the microconstants. The full (1)H, (13)C and (15)N NMR assignments, NMR-pH
      profiles, macro- and microprotonation schemes and species-specific diagrams are
      included. Our studies show that the fluoroquinolones have three protonation
      centers: the carboxylate group, the N-1' and N-4' piperazine nitrogens and
      concentration of the uncharged microspecies is way below the values published
      earlier. The results could be well interpreted in terms of structural properties.
      The protonation macro- and microconstant values allow the pre-planned method
      development in techniques such as capillary zone electrophoresis and also, the
      interpretation of fluoroquinolone mechanism of biological action, including the
      pharmacokinetic properties, and antibacterial activities that are all heavily
      influenced by the states of protonation.

PMID- 22464556
TI  - HPTLC method for the simultaneous determination of four indole alkaloids in
      Rauwolfia tetraphylla: a study of organic/green solvent and continuous/pulse
      sonication.
AB  - A new validated high-performance thin-layer chromatographic (HPTLC) method has
      been developed for the simultaneous quantitation of four antipsychotic indole
      alkaloids (IAs), reserpiline (RP, 1), alpha-yohimbine (YH, 2), isoreserpiline
      (IRP, 3) and 10-methoxy tetrahydroalstonine (MTHA, 4) as markers in the leaves of
      Rauwolfia tetraphylla. Extraction efficiency of the targeted IAs from the leaf
      matrix with organic and ecofriendly (green) solvents using percolation,
      ultrasonication and microwave techniques were studied. Non-ionic surfactants,
      viz. Triton X-100, Triton X-114 and Genapol X-80 were used for extraction and no
      back-extraction or liquid chromatographic steps were used to remove the targeted
      IAs from the surfactant-rich extractant phase. The optimized cloud point
      extraction was found a potentially useful methodology for the preconcentration of
      the targeted IAs. The separation was achieved on silica gel 60F(254) HPTLC plates
      using hexane-ethylacetate-methanol (5:4:1, v/v/v) as mobile phase. The
      quantitation of IAs (1-4) was carried out using the densitometric
      reflection/absorption mode at 520 nm after post chromatographic derivatization
      using Dragendorff's reagent. The method was validated for peak purity, precision,
      accuracy, robustness, limit of detection (LOD) and quantitation (LOQ). Method
      specificity was confirmed using retention factor (R(f)) and visible spectral
      (post chromatographic scan) correlation of marker compounds in the samples and
      standard tracks.

PMID- 22464557
TI  - Structural characterization of a novel degradant of the antifungal agent
      posaconazole.
AB  - A number of degradants of the antifungal agent posaconazole have been isolated
      and characterized. Degradation chemistry occurs primarily in the piperazine
      moiety located near the center of the molecule and typically involves oxidative
      processes. At least one ring contraction product has also been fully
      characterized by MS and NMR methods. We report the isolation and characterization
      of a novel degradant of posaconazole in which remnants of the piperazine ring
      have been incorporated into a 1,4-benzodiazepine moiety. The structure of the
      novel degradant was unequivocally established through accurate mass measurements,
      MS/MS studies, H/D exchange, and a range of 2D NMR experiments that included 1,1
      ADEQUATE and covariance calculated HSQC-1,1-ADEQUATE spectra.

PMID- 22464558
TI  - Towards a decade of detecting new analogues of sildenafil, tadalafil and
      vardenafil in food supplements: a history, analytical aspects and health risks.
AB  - The scale at which erectile dysfunction (ED) medicines are obtained outside of
      the official health system rivals and possibly exceeds legitimate sales.
      According to literature a high-risk segment of this market is occupied by
      adulterated food supplements. The principle adulterants identified were
      structural analogues of the registered ED drugs sildenafil, tadalafil, and
      vardenafil. Currently, at least 46 different analogues have been reported and
      still more are expected. The intellectual origin of analogues was found in patent
      literature which described the drug discovery process. Patent literature offers a
      flexible approach to synthesize hundreds of analogues. Most of the analogues
      currently known had long been disclosed in patent literature. Screening for (new)
      analogues is best carried out by using advanced LC-MS/MS techniques that focus on
      marker fragment ions. Analogues are experimental drugs in essence because most
      have no known efficacy or safety profile. Their use in seemingly harmless food
      supplements is expected to cause serious adverse effects. However, few reports
      have emerged in literature on actual harm. Considering the exposure to analogues
      and their adverse effects being unknown a gross underreporting of complaints is
      expected.

PMID- 22464559
TI  - Non-destructive detection of adulterated tablets of glibenclamide using NIR and
      solid-phase fluorescence spectroscopy and chemometric methods.
AB  - This study describes a method for non-destructive detection of adulterated
      glibenclamide tablets. This method uses near infrared spectroscopy (NIRS) and
      fluorescence spectroscopy along with chemometric tools such as Soft Independent
      Modeling of Class Analogy (SIMCA), Partial Least Squares-Discriminant Analysis
      (PLS-DA) and Unfolded Partial Least Squares with Discriminant Analysis (UPLS-DA).
      Both brand name (Daonil) and generic glibenclamide tablets were used for
      analysis. The levels of glibenclamide in each type of tablet were evaluated by
      derivative spectrophotometry in the ultraviolet region. The results obtained from
      the NIR and fluorescence spectroscopy along with those obtained from multivariate
      data classification show that this combined technique is an effective way to
      detect adulteration in drugs for the treatment of diabetes. In the future, this
      method may be extended to detect different types of counterfeit medications.

PMID- 22464560
TI  - beta-Cyclodextrin enhanced on-line organic solvent field-amplified sample
      stacking in capillary zone electrophoresis for analysis of ambroxol in human
      plasma, following liquid-liquid extraction in the 96-well format.
AB  - A field-amplified sample stacking (FASS) and capillary zone electrophoresis (CZE)
      method is described for the quantification of ambroxol hydrochloride in human
      plasma, following liquid-liquid extraction in the 96-well format. The separation
      was carried out at 25  degrees C in a 31.2 cm * 75 MUm fused-silica capillary
      with an applied voltage of 15 kV. The background electrolyte (BGE) was composed
      of 6.25 mM borate-25 mM phosphate (pH 3.0) and 1mM beta-cyclodextrin. The
      detection wavelength was 210 nm. Clean-up and preconcentration of plasma
      biosamples were developed by 96-well format liquid-liquid extraction (LLE). In
      this study, FASS in combination with beta-cyclodextrin enhanced the sensitivity
      about 60-70 fold in total. The method was suitably validated with respect to
      stability, specificity, linearity, lower limit of quantitation, accuracy,
      precision, extraction recovery and robustness. The calibration graph was linear
      for ambroxol hydrochloride from 2 to 500 ng/ml. The lower limit of quantification
      was 2 ng/ml. The intra- and inter-day precisions of lowest limit of
      quantification (LLOQ) were 9.61 and 11.80%, respectively. The method developed
      was successfully applied to the evaluation of clinical pharmacokinetic study of
      ambroxol hydrochloride tablet after oral administration to 12 healthy volunteers.

PMID- 22464561
TI  - Critical review of near-infrared spectroscopic methods validations in
      pharmaceutical applications.
AB  - Based on the large number of publications reported over the past five years, near
      infrared spectroscopy (NIRS) is more and more considered an attractive and
      promising analytical tool regarding Process Analytical Technology and Green
      Chemistry. From the reviewed literature, few of these publications present a
      thoroughly validated NIRS method even if some guidelines have been published by
      different groups and regulatory authorities. However, as any analytical method,
      the validation of NIRS method is a mandatory step at the end of the development
      in order to give enough guarantees that each of the future results during routine
      use will be close enough to the true value. Besides the introduction of PAT
      concepts in the revised document of the European Pharmacopoeia (2.2.40) dealing
      with near-infrared spectroscopy recently published in Pharmeuropa, it agrees very
      well with this mandatory step. Indeed, the latter suggests to use similar
      analytical performance characteristics than those required for any analytical
      procedure based on acceptance criteria consistent with the intended use of the
      method. In this context, this review gives a comprehensive and critical overview
      of the methodologies applied to assess the validity of quantitative NIRS methods
      used in pharmaceutical applications.

PMID- 22464562
TI  - Sensitive detection of carcinoembryonic antigen with magnetic nano-bead and
      upconversion nanoparticles-based immunoassay.
AB  - A novel magnetic nanobead-based immunoassay was developed for the quantification
      of carcinoembryonic antigen (CEA) in human serum in this study. Amine
      functionalized Fe(3)O(4) magnetic nanoparticles (MNPs) were conjugated with
      capture anti-CEA antibodies and amine-functionalized NaY(0.78)F(4):Yb(0.20),
      Ho(0.02) upconversion nanoparticles (UCNPs) were synthesized and conjugated with
      detection anti-CEA antibodies, respectively. Based on a sandwich-type immunoassay
      format, the detection limit for CEA under optimal conditions was as low as 2.5
      pg/mL, and the linear range of CEA detection was from 2.5*10(-12) to 1*10(-8)
      g/mL (I=406.19 logX+428.81) with a correlation coefficient equal to 0.9987. The
      established method was successfully applied to measure CEA in human serum samples
      and more sensitive than a commercially available chemiluminescence method. The
      precision expressed as the relative standard deviation of CEA detection was equal
      to 5.19% (1 ng/mL) or 4.36% (5 pg/mL), indicating that the developed method
      exhibited good reproducibility. The results demonstrate that the method offers
      potential advantages of sensitivity and good reproducibility for the
      determination of CEA, and is applicable to the determination of CEA in serum
      samples.

PMID- 22464563
TI  - Quantification of main bioactive metabolites from saffron (Crocus sativus)
      stigmas by a micellar electrokinetic chromatographic (MEKC) method.
AB  - Saffron is an expensive spice, cultivated in many regions of the world. Its chief
      metabolites include crocins, which are responsible for the coloring ability,
      safranal, which is the main essential oil constituent, and picrocrocin which is
      the main bitter constituent of the spice. A simple micellar capillary
      electrochromatographic (MEKC) method capable of quantifying all three types of
      main constituents was established. The pH, sodium dodecyl sulphate (SDS) content
      and electrolyte concentration of the background electrolyte was optimized. A
      simple extraction protocol was developed which can extract all metabolites of
      different polarity from the saffron stigmas. Optimal background electrolyte
      composed of 20 mM disodium phosphate, 5mM sodium tetraborate, 100 mM SDS, pH was
      set 9.5. Optimal extracting solvent was the background electrolyte, incubated
      with the sample for 60 min. The proposed method allows quantification of
      picrocrocin, safranal, crocetin- Di-(beta-D-gentiobiosyl) ester and crocetin
      (beta-D-glycosyl)-(beta-D-gentiobiosyl) ester within 17.5 min, with limit of
      detection values ranging from 0.006 to 0.04 mg/ml, from a single stigma.

PMID- 22464565
TI  - Severe aortic or pulmonary valve stenosis in premature infants.
AB  - Successful treatment of severe aortic (AS) or pulmonary valve (PS) stenosis by
      balloon valvuloplasty in term neonates is well-established. Sometimes, AS or PS
      diagnosed antenatally, progresses to severe left or right ventricular hypoplasia
      respectively. Successful fetal balloon valvuloplasty cannot be assumed to
      significantly change the natural history. In this review of premature infants,
      balloon valvuloplasty was used in extremely small babies. Five with severe AS (32
      to 36 weeks, birth weight 1.4 to 1.9 kg) had percutaneous balloon aortic
      valvuloplasty during the first 10 days of life. Seven infants with
      severe/critical PS (28 to 36 weeks, birth weight 1.2 to 1.9 kg) had percutaneous
      balloon pulmonary valvuloplasty during the first 9 days of life. Two with
      pulmonary atresia (1.9 and 0.85 kg), underwent successful radiofrequency assisted
      balloon pulmonary valvuloplasty. There were no procedural deaths but one infant
      developed severe aortic insufficiency.

PMID- 22464564
TI  - Hand weakness in Charcot-Marie-Tooth disease 1X.
AB  - There have been suggestions from previous studies that patients with Charcot
      Marie-Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to
      date have included a heterogeneous group of CMT patients we decided to analyse
      hand strength in 43 patients with CMT1X. We recorded handedness and the MRC
      scores for the first dorsal interosseous and abductor pollicis brevis muscles,
      median and ulnar nerve compound motor action potentials and conduction velocities
      in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker
      dominant hand; none had a stronger dominant hand. Mean MRC scores were
      significantly higher for first dorsal interosseous and abductor pollicis brevis
      in non-dominant hands compared to dominant hands. Median nerve compound motor
      action potentials were significantly reduced in dominant compared to non-dominant
      hands. We conclude that the dominant hand is weaker than the non-dominant hand in
      patients with CMT1X.

PMID- 22464567
TI  - [The urgent management dependent on the patient's benefit in emergency
      cardiovascular care].

PMID- 22464566
TI  - Early fetal echocardiography and anomaly scan in fetuses with increased nuchal
      translucency.
AB  - Nuchal translucency (NT) identified at the time of the 11-14 week scan has been
      established as one of the best tools for screening for Down syndrome. It has also
      proven to be of value in screening for other conditions such as cardiac defects
      and extra-cardiac structural abnormalities. In this article, we present data from
      our fetal medicine unit that highlight the importance of using NT measurement as
      a stratifying tool when referring for early scans. We propose that, whenever
      possible, in selected cases with increased NT, provision should be made for
      additional early scans at 14-18 weeks of gestation with a view to providing
      information on fetal structural integrity well ahead of the routine scheduled
      appointments. Early scans should incorporate detailed assessment of the fetal
      cardiac as well as extra-cardiac anatomy to diagnose or rule out major structural
      defects. This strategy will provide reassurance to a large number of prospective
      parents.

PMID- 22464568
TI  - [Heart as a neuroendocrine organ].

PMID- 22464569
TI  - [The protective effects of insulin on cardiocyte apoptosis challenged by burn
      serum].
AB  - OBJECTIVE: To investigate the protective effects of insulin on burn serum
      challenged cardiocyte apoptosis and its mechanism. METHODS: Burn-serum challenged
      cardiocytes were pretreated with insulin and inhibitors to pathway SB203580 and
      LY294002. The expression of cardiac myofilament proteins cleaved-caspase-3, Bax
      and phosphorylation nuclear factor-KappaB inhibitive factor alpha (p
      IKappaBalpha) were examined by Western blotting. The mRNA expression of tumor
      necrosis factor-alpha (TNF-alpha) was determined by real-time reverse
      transcription-polymerase chain reaction (RT-PCR). Apoptosis of cardiocyte was
      observed after Hoechst 33258 staining. Further blocking experiments were used to
      investigate the cytoprotective pathway of insulin. RESULTS: Insulin could
      significantly decrease the expression of cleaved-caspase-3 (2.22 +/- 0.30  vs. 
      4.84 +/- 0.74, P < 0.01), Bax (1.33 +/- 0.35  vs.  3.74 +/- 0.65, P < 0.01), p
      IKappaBalpha (1.43 +/- 0.62  vs.  3.62 +/- 0.74, P < 0.01), TNF-alpha (0.72 +/-
      0.27  vs.  2.02 +/- 0.63, P < 0.01) and the cardiocyte apoptosis rate [(9.4 +/-
      3.4)%  vs.  (19.1 +/- 5.6)%, P < 0.01] in cardiocytes challenged by burn serum.
      Further blocking experiments showed that LY294002, phosphatidylinositol-3-kinase
      (PI3K)/Akt activation inhibitor, could mitigate the protective effects of
      insulin. Meanwhile, SB203580, an inhibitor of p38 mitogen-activated protein
      kinase (p38MAPK) pathway, was able to inhibit cardiocyte injury challenged by
      burn serum, and it was as effective as insulin. CONCLUSION: For cardiocytes
      challenged by burn serum, insulin may decrease inflammatory cytokine expression
      and apoptosis via regulating PI3K/Akt and p38MAPK pathway.

PMID- 22464570
TI  - [Effect of intensive glucose control during peri-operative period on prognosis of
      patients undergoing cardiac surgery: a Meta-analysis].
AB  - OBJECTIVE: To systematically review the literature to determine the effects of
      intensive versus normal glycaemic control during peri-operative period on
      prognosis of patients undergoing cardiac surgery. METHODS: The literature was
      systematically reviewed based on searching criteria established by Cochrane
      Collaboration. PubMed database searching was conducted for literature and the
      language was limited to English. Each  paper  was  reviewed  by 2 independent
      reviewers and data extracted for statistical analysis. Data from identified
      studies were collected for Meta-analysis (RevMan 5.0). RESULTS: Seven randomized
      controlled trials (RCTs), involving a total of 2329 patients, were identified in
      the literature. The results showed that intensive glycaemic control could reduce
      the incidence of infection [odds ratio (OR) = 0.42, 95% confidence interval
      (95%CI) 0.25 to 0.73, P = 0.002], mortality (OR = 0.54, 95%CI 0.34 to 0.87, P =
      0.01), the  duration  of mechanical ventilation [weighted mean difference (WMD) =
      -2.68, 95%CI -4.99 to -0.37, P = 0.02], and length of stay in the intensive care
      unit (ICU, WMD = -15.49, 95%CI -16.14 to -14.83, P < 0.000 01), and also could
      slightly reduce the incidence of post-surgical atrial fibrillation (OR = 0.77,
      95%CI 0.60 to 1.00, P = 0.05). However, intensive glycaemic control could not
      reduce the use of epicardial pacing (OR = 0.32, 95%CI 0.09 to 1.05, P = 0.06).
      CONCLUSION: Intensive blood glucose control during peri-operative period could
      improve the prognosis of patients undergoing cardiac surgery.

PMID- 22464571
TI  - [Study on the pathogenesis of stress myocardial injury].
AB  - OBJECTIVE: To investigate  the  pathogenesis of stress myocardial  injury.
      METHODS: Thirty Wistar rats were randomly divided into three groups, with 10 rats
      in each group: normal control group, movement restriction and ice swimming stress
      group (rat movement was restricted 6 hours per day; beginning from 13th day rats
      were allowed to swim in ice water for 5 minutes, ice stress group), and endotoxin
      stress group [intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg, LPS
      group]. The myocardial tissue was harvested, the pathological changes in
      myocardial was observed with light microscopy, and the changes in myocardial
      ultrastructure were observed with electron microscope. The levels of serum
      cardiac troponin I (cTnI) was determined by enzyme-linked immunosorbent assay
      (ELISA), apoptosis of myocardial cells was detected by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and the
      apoptotic index was calculated.The caspase-8 and caspase-3 expression in
      myocardial tissue were assessed by immunohistochemistry. The correlation between
      caspase and apoptotic index was analyzed. RESULTS: Compared with normal control
      group, in ice stress group and LPS group, myocardial tissue was found to be
      injured seriously in different degrees under light microscopy and electron
      microscopy; the content of cTnI (MUg/L) in serum was significantly increased
      (0.63 +/- 0.12, 0.74 +/- 0.08  vs.  0.53 +/- 0.03, P < 0.05 and P < 0.01);
      apoptosis index of myocardial tissue was significantly increased in different
      degrees [(7.91 +/- 1.71)%, (12.94 +/- 2.00)%  vs.  0]; caspase-8 and caspase-3
      expressions in the myocardium were increased (caspase-8 gray scale: 126.65 +/-
      3.13, 114.82 +/- 8.67  vs.  156.99 +/- 9.66; caspase-3 gray scale: 130.20 +/-
      2.96, 108.58 +/- 5.72  vs.  160.51 +/- 5.25, all P < 0.01). However, the above
      indexes in LPS group were significantly higher than those in ice stress group (P
      < 0.05 or P < 0.01). The correlation analysis showed that in ice stress group,
      positive correlation was found between caspase-8, caspase-3 and apoptotic index
      [r(1) = 0.914, P(1) = 0.002; r(2) = 0.929, P(2) = 0.001]; in LPS group, the
      positive correlation also exist between caspase-8, caspase-3 and apoptotic index
      [r(1) = 0.956, P(1) = 0.000; r(2) = 0.916, P(2) = 0.001]. CONCLUSION: Severe
      stress may produce stress injury of myocardium via increasing expression of
      caspase-8 and caspase-3 protein.

PMID- 22464572
TI  - [Proteomics analysis of myocardium after delayed preconditioning with hydrogen
      sulfide in rat].
AB  - OBJECTIVE: To investigate the changes in protein of myocardium after hydrogen
      sulfide delayed preconditioning by using proteomics technology. METHODS: Sixteen
      Sprague-Dawley rats were randomly assigned to control (group S) or hydrogen
      sulfide group (group H), n = 8 for each group. Myocardial ischemia/reperfusion
      injury model (ischemia 30 minutes followed by reperfusion 120 minutes) was
      reproduced at 24 hours after preconditioning either with normal saline or
      hydrogen sulfide for proteomics analysis in group S or group H, and the
      myocardial tissue was harvested. The total proteins were extracted and separated
      by two dimensional gel electrophoresis (2-DE), and the differential protein
      expression spots were analyzed with matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: Analysis of 2-DE showed
      that 929 +/- 14 protein spots were found in group S and 906 +/- 10 protein spots
      in group H, and the expression of 15 protein spots was different between two
      groups. These protein spots were chosen to undergo MALDI-TOF-MS analysis, and 11
      proteins were preliminarily identified, including DNA ligase, cystathionine gamma
      lyase, transcription initiation factor, NADH dehydrogenase, guanine nucleotide
      releasing factor, fructose-bisphosphate aldolase A, glycogen synthase kinase-3,
      electron transfer flavoprotein subunit beta, glutathione S-transferase, soluble
      calcium-activated nucleotidase and S-adenosylmethionine synthetase. CONCLUSIONS:
      Hydrogen sulfide delayed preconditioning of myocardium resulted in the changes in
      protein expression profiles in the myocardium. The differential proteins might
      function as anti-oxidants, to improve the energy metabolism of myocardium, confer
      cytoprotection and protection of respiratory chain, thus conferring
      cardioprotection.

PMID- 22464573
TI  - [The influence of statin therapy on circulating microRNA-92a expression in
      patients with coronary heart disease].
AB  - OBJECTIVE: To investigate the modulatory function of statin therapy on
      circulating microRNA-92a (miR-92a) in patients with coronary heart disease (CHD),
      and to evaluate the possibility of miR-92a as a new target of treatment for
      endothelial dysfunction. METHODS: A case control study was conducted. Prevalence
      of abnormal blood fat content, statin treatment rate, and attainment rate of low
      density lipoprotein-cholesterol (LDL-C) lowered to expected level in 236 patients
      with CHD were analyzed. Relationship between statin therapy in patients with type
      2 diabetes mellitus (DM), and level of LDL-C and circulating miR-92a expression
      was analyzed by multivariate general linear factorial analysis. The incidence of
      acute coronary syndrome (ACS) was compared in patients with CHD receiving statin
      therapy in all groups. RESULTS: Prevalence of abnormal LDL-C was 95.7% (112/117)
      in CHD patients of non-statin therapy group, and 47.5% (112/236) of patients with
      CHD who should receive statin therapy but did not. Attainment rate of lowering of
      LDL-C to expected level in statin therapy group was 27.7% (33/119). LDL-C level
      (mmol/L) was significantly lower in statin therapy group than that in non-statin
      therapy group (2.457 +/- 0.802 vs. 3.218 +/- 1.130, Z = -9.760, P = 0.001), and
      incidence of ACS was significantly lower in statin therapy group than that in non
      statin therapy group [33.6% vs. 71.8%, chi(2) = 34.491, P = 0.001]. There was no
      significant difference in incidence of ACS between patients with or without
      attaining the expected low value of LDL-C in statin therapy group [33.3% vs.
      33.7%,chi(2) = 0.002, P = 0.968]. Circulating miR-92a expression was
      significantly higher in patients with stable angina pectoris (SAP) complicated
      with DM than those without DM (0.492 vs. -0.121, Z = -3.038, P = 0.002). It was
      found that statin therapy could down regulate miR-92a expression in patients with
      SAP complicated with DM as compared with that with non-statin therapy (0.419 vs.
      0.687, Z = 1.289, P = 0.072). There was no significant difference in circulating
      miR-92a expression between statin therapy and non-statin therapy in patients with
      SAP without co-existing DM (-0.032 vs. -0.198, Z = -0.614, P = 0.539).
      Multivariate general linear factorial analysis showed that statin therapy was the
      major influential factor on LDL-C level in patients with CHD (F = 22.863, P =
      0.001), and complicating DM was the major influential factor on circulating miR
      92a expression in patients with SAP (F = 9.641, P = 0.003). CONCLUSION:
      Regulation of circulating miR-92a expression may be considered as a new clinical
      target for statin treating endothelial dysfunction in patients with CHD.

PMID- 22464574
TI  - [Effects of mild hypothermia on low cardiac output after cardiac surgery].
AB  - OBJECTIVE: To evaluate the effectiveness of mild hypothermia on low cardiac
      output in patients after cardiac surgery. METHODS: Twelve patients manifesting
      low cardiac output after cardiac surgery despite of the use of massive doses of
      catecholamine and intra-aortic balloon pump (IABP) underwent mild hypothermia
      during May 2009 to February 2011. Changes in hemodynamic parameters of the
      patients were measured, including cardiac index (CI),mixed venous oxygen
      saturation [SvO(2)] and urine volume. RESULTS: In the process of mild hypothermia
      treatment, bladder temperature of patients was lowered to 33-35 centigrade in
      order to reduce the body oxygen demand. The CI [ml.s(-1).m(-2)]of patients after
      mild hypothermia treatment was increased obviously (38.34 +/- 5.00 vs. 30.01 +/-
      5.00), the same as SvO(2) (0.64 +/- 0.07 vs. 0.54 +/- 0.08) and urine output
      [ml.kg(-1).h(-1): 3.0 +/- 2.1 vs. 1.5 +/- 1.1, all P < 0.05]. However, there was
      no significant change in heart rate, mean arterial pressure and blood oxygen
      pressure. CONCLUSION: Mild hypothermia is an effective and simple procedure to
      improve the cardiac function in patients after cardiac surgery complicated with
      low cardiac output.

PMID- 22464575
TI  - [Effects of fluid resuscitation on myocardial injury in patients with severe
      sepsis and septic shock].
AB  - OBJECTIVE: To observe the influence of fluid resuscitation on patients suffered
      from myocardial injury with severe sepsis and septic shock, and to evaluate the
      markers of myocardial injury during fluid resuscitation. METHODS: Acute
      physiology and chronic health evaluation II (APACHE II) score of 78 patients with
      severe sepsis and septic shock induced by combined injuries was 18-35. Serum
      cardiac troponin I (cTnI), N-terminal-ventricular natriuretic peptide precursor
      (NT-proBNP) and the hemodynamic parameters were recorded before, 3 days, and 5
      days after treatment, and correlative analysis was conducted. RESULTS: Serum cTnI
      was increased in 62.8% (49/78) patients with severe sepsis and septic shock, and
      in 73.5% of patients (36/49) the increase was greater than 2-fold of the
      borderline value, and in 30.6% of patients (15/49) was greater than 4-fold of the
      borderline value. The patients with elevated serum NT-proBNP at admission
      accounted for 46.2% (36/78), and after fluid resuscitation treatment, patients
      with continuously rising value accounted for 74.4% (58/78). The serum cTnI, NT
      proBNP, pulmonary arterial wedge pressure (PAWP) and cardiac index (CI) after
      treatment in survival group (55 cases) were obviously improved, and changes in
      them in non-survival group (23 cases) was not obvious. The serum cTnI (MUg/L) and
      NT-proBNP (ng/L) levels in the non-survival group were distinctly higher than
      those of the survival group (cTnI 3 days: 2.09 +/- 1.00 vs. 1.57 +/- 0.93, 5
      days: 1.78 +/- 0.67 vs. 0.72 +/- 0.51; NT-proBNP 3 days: 3.52 +/- 0.73 vs. 3.16
      +/- 0.65, 5 days: 3.21 +/- 0.66 vs. 2.66 +/- 0.58), and CI [ml.s(-1).m(-2)] was
      obviously lower than that of the survival group (3 days: 57.6 +/- 6.2 vs. 68.3 +/
      5.6, 5 days: 40.5 +/- 4.7 vs. 80.7 +/- 6.8, all P < 0.05). The cTnI level
      (MUg/L) of 46 patients whose fluid resuscitation achieved the target was lower
      than that of the 32 cases without achieving the target (1.16 +/- 0.62 vs. 1.97 +/
      0.76, P < 0.05), and the CI [ml.s(-1).m(-2)] was obviously increased (61.2 +/-
      6.4 vs. 49.3 +/- 6.1, P < 0.05). The results suggested that whether the fluid
      resuscitation achieved the target or not was not related to changes in serum NT
      proBNP and PAWP. A positive correlation was found between serum cTnI and NT
      proBNP (r = 0.865, Y = 2.069 + 0.695X, P < 0.01), also between NT-proBNP and PAWP
      (r = 0.762, Y = 1.125 + 4.929X, P < 0.01), and a negative correlation was found
      between cTnI and CI (r = -0.891, Y = 50.623 - 6.114X, P < 0.01). CONCLUSIONS:
      There is an obvious myocardial injury in the patient with severe sepsis and
      septic shock, and fluid resuscitation can improve the myocardial injury; the
      serum levels of cTnI and NT-proBNP are related to the prognosis of patients, but
      the significance of NT-proBNP guiding the fluid resuscitation can not be
      ascertained.

PMID- 22464576
TI  - [Changes in coagulation and fibrinolysis in the patients with coronary heart
      disease in acute period and effect of drug intervention].
AB  - OBJECTIVE: To investigate the changes in coagulation and fibrinolysis parameters
      during acute phase of coronary heart disease, and to explore the effects of drug
      intervention in same period. METHODS: A prospective study was conducted. The
      changes in plasma von Willebrand factor (vWF), platelet activating factor (PAF),
      tissue type plasminogen activator (t-PA) of 110 patients with coronary heart
      disease [50 patients with acute myocardial infarction (AMI), 35 patients with
      unstable angina pectoris (UAP), 25 patients with ischemic cardiomyopathy (ICM)]
      were determined immediately at admission and 14 days after treatment. The indexes
      of 19 healthy individuals were collected as control. At the same time, randomized
      and double-blind observation of the changes in plasma coagulation and
      fibrinolysis system indexes including vWF, PAF and t-PA was made in AMI and UAP
      patients who received conventional treatment (aspirin + low molecular weight
      heparin) or combination of conventional treatment and clopidogrel for 14 days.
      RESULTS: The vWF and PAF levels (nmol/L) of AMI and UAP patients at admission
      were significantly higher than those in healthy control group [vWF: (202.31 +/-
      27.38)%, (188.65 +/- 31.08)%  vs.  (120.37 +/- 18.79)%; PAF: 50.64 +/- 13.25,
      48.87 +/- 13.24  vs.  15.43 +/- 9.27, all P < 0.05], however, t-PA (MUg/L) was
      remarkably lower than that in healthy control group (3.52 +/- 1.57, 4.03 +/- 2.04
      vs.  9.54 +/- 1.32, both P < 0.01). After 14 days of treatment, the levels of
      vWF, PAF, t-PA, fibrinogen (Fib, g/L), D-dimer (mg/L) in plasma of AMI and UAP
      patients were close to those of healthy control group [vWF: (116.56 +/- 26.10)%,
      (111.28 +/- 22.31)%  vs.  (120.37 +/- 18.79)%; PAF: 17.48 +/- 9.16, 16.23 +/-
      9.17  vs.  15.43 +/- 9.27; t-PA: 7.91 +/- 2.42, 9.01 +/- 2.01  vs.  9.54 +/-
      1.32; Fib: 3.64 +/- 0.53, 2.74 +/- 0.72  vs.  2.92 +/- 0.91; D-dimer: 0.370 +/-
      0.150, 0.288 +/- 0.169  vs.  0.255 +/- 0.109, all P>0.05]. However, there was no
      statistical difference in vWF, PAF, t-PA, Fib and D-dimer levels before and after
      treatment in ICM group compared with healthy control group [vWF: (124.14 +/-
      21.17)%, (119.44 +/- 26.28)%  vs.  (120.37 +/- 18.79)%; PAF: 15.69 +/- 7.14,
      14.84 +/- 9.16  vs.  15.43 +/- 9.27; t-PA: 8.62 +/- 2.24, 8.07 +/- 2.51  vs. 
      9.54 +/- 1.32; Fib: 3.24 +/- 0.74, 3.04 +/- 0.77  vs.  2.92 +/- 0.91; D-dimer:
      0.257 +/- 0.132, 0.268 +/- 0.117  vs.  0.255 +/- 0.109, all P>0.05]. Multiple
      linear regression analysis showed that, in patients with coronary heart disease,
      PAF be positively correlated with vWF (r = 0.42, P < 0.01), but negatively
      correlated with t-PA (r = -0.31, P < 0.01). In patients with AMI and UAP, using
      the treatment of clopidogrel for 14 days, the levels of vWF, PAF, t-PA, Fib and D
      dimer in plasma showed no significant differences compared with those of
      conventional treatment group [vWF: (120.16 +/- 16.57)%  vs.  (118.12 +/- 14.32)%;
      PAF: 12.01 +/- 3.70  vs.  13.33 +/- 1.10; t-PA: 9.75 +/- 1.60  vs.  7.59 +/-
      2.46; Fib: 2.73 +/- 0.49  vs.  3.09 +/- 0.50; D-dimer: 0.233 +/- 0.101  vs. 
      0.252 +/- 0.088, all P>0.05]. CONCLUSIONS: There were changes in coagulation and
      fibrinolysis status in patients with AMI and UAP at the initial stage, the level
      of t-PA was decreased significantly. For patients with AMI and UAP, there were no
      obvious differences in coagulation and fibrinolysis parameters between
      combination therapy of clopidogrel and aspirin and aspirin alone.

PMID- 22464577
TI  - [Effects of extracorporeal membrane oxygenation on hemodynamics in acute right
      heart failure in dogs].
AB  - OBJECTIVE: To investigate the effects of extracorporeal membrane oxygenation
      (ECMO) on the hemodynamics in dogs with acute right heart failure. METHODS: Ten
      healthy adult male dogs (weighted 20-25 kg) were randomly divided into two
      groups: acute right heart failure group (n = 5) and ECMO group (n = 5). Under
      anesthesia, dogs  were underwent thoracotomy, then the catheters were placed in
      the right atrium, right ventricle, and pulmonary artery, for measuring the
      relevant pressures, including right arterial pressure (RAP), right ventricular
      pressure (RVP), and pulmonary artery pressure (PAP). The vascular ultrasound
      probe were placed on the aorta and pulmonary artery for measuring the cardiac
      output (CO) and pulmonary artery flow rate (QPA). Then, a baseline measurement
      was acquired. The femoral artery and femoral vein were cannulated and used for
      the venoarterial extracorporeal membrane oxygenation (VA-ECMO), and then
      connected to extracorporeal circuit, which was initially primed. The pulmonary
      artery was progressively ligated to decrease blood flow until QPA was 60%, 40%,
      and 0% of baseline in both groups. The above flow conditions were respectively
      maintained for 30 minutes, after which hemodynamic data were collected. RESULTS:
      The baseline hemodynamic measurements were not different between acute right
      heart failure group and ECMO group. After ligating the pulmonary artery, compared
      with baseline, CO (L/min) decreased significantly at 60% and 40% QPA in acute
      right heart failure group (1.80 +/- 0.19, 1.48 +/- 0.22  vs.  3.24 +/- 0.23, both
      P < 0.05), and significantly lower than that of ECMO group (60%QPA: 1.80 +/- 0.19
      vs.  3.24 +/- 0.35; 40%QPA: 1.48 +/- 0.22  vs.  3.20 +/- 0.37, both P < 0.05).
      CO was not significantly different from baseline in ECMO group at 60%, 40% and 0%
      QPA (3.24 +/- 0.35, 3.20 +/- 0.37, 3.12 +/- 0.28  vs.  3.44 +/- 0.32, all
      P>0.05). PAP, RAP and RVP (all mm Hg, 1 mm Hg = 0.133 kPa) were significantly
      elevated in acute right heart failure group at 60% and 40% QPA compared with
      baseline (PAP: 36.2 +/- 5.3, 39.8 +/- 5.4  vs.  17.4 +/- 2.7; RAP: 11.2 +/- 2.8,
      12.8 +/- 2.6  vs.  4.4 +/- 1.7; RVP: 25.6 +/- 4.9, 27.8 +/- 4.5  vs.  11.6 +/-
      1.8, all P < 0.05), and significantly higher than those of ECMO group (60%QPA:
      PAP 36.2 +/- 5.3  vs.  23.2 +/- 5.2, RAP 11.2 +/- 2.8  vs.  6.2 +/- 2.3, RVP 25.6
      +/- 4.9  vs.  15.2 +/- 3.5; 40%QPA: PAP 39.8 +/- 5.4  vs.  24.4 +/- 4.8, RAP 12.8
      +/- 2.6  vs.  7.0 +/- 2.4, RVP 27.8 +/- 4.5  vs.  16.8 +/- 4.2, all P < 0.05),
      whereas mean artery pressure (MAP, mm Hg) was significantly lowered compared with
      that of baseline (81.2 +/- 15.8, 62.2 +/- 14.4  vs.  128.6 +/- 16.4, both P <
      0.05), and it was lower than that of ECMO group (60%QPA: 81.2 +/- 15.8  vs. 
      128.0 +/- 26.5; 40%QPA: 62.2 +/- 14.4  vs.  124.6 +/- 25.4, both P < 0.05). At
      60%, 40% and 0% QPA in ECMO group, whereas heart rate (HR, beats/min), PAP, RAP
      and RVP were slightly increased compared with those of baseline (HR: 161.4 +/-
      14.8, 160.6 +/- 13.1, 157.6 +/- 11.9  vs.  152.6 +/- 14.5; PAP: 23.2 +/- 5.2,
      24.4 +/- 4.8, 25.2 +/- 6.2  vs.  18.8 +/- 3.4; RAP: 6.2 +/- 2.3, 7.0 +/- 2.4, 7.6
      +/- 4.2  vs.  4.6 +/- 1.5; RVP: 15.2 +/- 3.5, 16.8 +/- 4.2, 16.2 +/- 3.3  vs. 
      12.2 +/- 2.3), but MAP was slightly decreased (128.0 +/- 26.5, 124.6 +/- 25.4,
      121.2 +/- 21.4  vs.  135.8 +/- 22.2), however, all differences were not
      statistically significant (all P>0.05). CONCLUSION: These findings demonstrate
      that VA-ECMO could be helpful in improving cardiac function, and maintaining
      stability of hemodynamics in dogs with acute right heart failure.

PMID- 22464578
TI  - [Effect of Xuebijing injection on rabbits ischemia/reperfusion injury induced by
      femoral arterial disease].
AB  - OBJECTIVE: To investigate the changes in serum malondialdehyde (MDA), interleukin
      1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), aspartate
      aminotransferase (AST) and creatinine (Cr) after the reproduction of
      ischemia/reperfusion (I/R) injury model, and the protective effects of liver and
      kidney with Xuebijing injection on acute I/R injury in rabbits. METHODS: Sixty
      rabbits were divided into six groups with a random number: A, normal group; B,
      sham operated group; C, model group, and D, E, F groups (Xuebijing low, middle,
      high dosage treatment groups). I/R injury model was reproduced (after a 4-hour
      ischemia, the femoral vessels were reperfusion). Physiological saline (2 ml/kg)
      or 0.33, 0.66 and 1.32 g/kg Xuebijing injection were given at 0, 12, 36, 60 hours
      after operation via ear vein. MDA, IL-1beta, TNF-alpha, AST and Cr were
      determined at 6, 12, 24 and 72 hours after reperfusion in each group. RESULTS:
      MDA, IL-1beta, TNF-alpha at different time points, AST and Cr at 72 hours after
      reperfusion in C group were significantly higher than those in A group and B
      group. Compared with the C group, the above indexes were gradually decreased with
      does-dependence, the values of MDA (MUmol/L), IL-1beta (ng/L) and TNF-alpha
      (MUg/L) in serum of group F at 6, 12, 24 and 72 hours after reperfusion were
      significantly lower (MDA: 9.74 +/- 3.71  vs.  12.35 +/- 4.64, 11.26 +/- 4.14  vs.
      12.82 +/- 3.85, 9.72 +/- 2.25  vs.  13.30 +/- 2.83, 9.12 +/- 2.72  vs.  13.10 +/
      2.72; IL-1beta: 83.49 +/- 12.79  vs.  100.09 +/- 17.53, 85.10 +/- 11.75  vs. 
      102.64 +/- 19.64, 75.97 +/- 11.29  vs.  99.24 +/- 14.62, 81.96 +/- 14.81  vs. 
      99.59 +/- 12.05; TNF-alpha: 8.95 +/- 1.13  vs.  9.94 +/- 1.29, 8.79 +/- 1.80  vs.
      9.56 +/- 0.89, 8.27 +/- 1.83  vs.  9.51 +/- 1.32, 7.23 +/- 1.39  vs.  9.23 +/-
      1.05, P < 0.05 or P < 0.01). The values of AST(U/L) and Cr (MUmol/L) in serum of
      groups D, E and F at 24 hours and 72 hours after reperfusion were significantly
      lower (AST 24 hours: 24.00 +/- 1.27, 23.80 +/- 1.11, 22.90 +/- 1.65  vs.  39.50
      +/- 1.73, 72 hours: 32.15 +/- 1.95, 32.90 +/- 1.77, 32.25 +/- 2.25  vs.  52.86 +/
      2.43; Cr 24 hours: 273.78 +/- 17.04, 267.07 +/- 19.59, 265.25 +/- 15.59  vs. 
      347.60 +/- 18.83, 72 hours: 437.38 +/- 18.48, 343.77 +/- 16.79, 351.48 +/- 20.22 
      vs.  437.50 +/- 19.86, all P < 0.01). CONCLUSIONS: It is demonstrated that I/R
      injury could dramatically lead to systemic inflammatory response and oxygen free
      radical injury. Xuebijing injection in higher dosage can reduce the systemic
      inflammatory response significantly, and also MDA level in serum. Xuebijing
      injection in low dosage, middle dosage and high dosage can produce protective
      effects against the damages to liver and kidney function.

PMID- 22464579
TI  - [An experimental study on the effects of rhythmic abdominal lifting and
      compression during cardiopulmonary resuscitation in a swine model of asphyxia].
AB  - OBJECTIVE: To compare the hemodynamic and respiratory influences of chest
      compression- cardiopulmonary resuscitation (CC-CPR) and rhythmic abdominal
      lifting and compression-cardiopulmonary resuscitation (ALC-CPR) in a swine model
      of asphyxia cardiac arrest (CA), and evaluate the effectiveness of rhythmic
      abdominal lifting and compression. METHODS: Thirty swines were randomly divided
      into two groups, with 15 swines in each group. CA model was reproduced by
      asphyxia as a result of clamping the trachea, and CC-CPR and ALC-CPR was
      conducted in two groups, respectively. Electrocardiogram (ECG), pulse oxygen
      saturation [SpO(2)], end-tidal partial pressure of carbon dioxide [P(ET)CO(2)],
      aorta systolic blood pressure (SBP), diastolic blood pressure (DBP), central
      venous pressure (CVP), and tidal volume (VT) were monitored continuously from 10
      minutes before asphyxia to the end of experiment. The aorta mean arterial
      pressure (MAP), coronary perfusion pressure (CPP) and minute ventilation (MV)
      were calculated. Artery blood samples were collected to determine the blood gas
      analysis at 10 minutes before asphyxia, 10 minutes after asphyxia, and 5, 10, 20
      minutes after resuscitation. The restoration of spontaneous circulation (ROSC)
      rate, 24-hour survival rate and 24-hour neurological function score were
      observed. RESULTS: There were no significant differences in all mentioned indexes
      between two groups at 10 minutes before and 10 minutes after asphyxia. At 2
      minutes after the resuscitation, the MAP (mm Hg, 1 mm Hg = 0.133 kPa) and CPP (mm
      Hg) in CC-CPR group were significantly higher than those in ALC-CPR group (MAP:
      43.60 +/- 12.91 vs. 33.40 +/- 6.59, P < 0.05; CPP: 21.67 +/- 11.28 vs. 11.80 +/-
      4.16, P < 0.01), the VT (ml) and MV (L/min)in ALC-CPR group were significantly
      higher than those in CC-CPR group (VT: 111.67 +/- 18.12 vs. 56.60 +/- 7.76; MV:
      11.17 +/- 1.81 vs. 5.54 +/- 0.79, both P < 0.01). At 5, 10, 20 minutes after
      resuscitation, in ALC-CPR group, pH value, arterial partial pressure of oxygen
      [PaO(2), mm Hg] and arterial oxygen saturation [SaO(2)] were increased, and
      HCO(3)(-) (mmol/L) and base excess (BE, mmol/L) were decreased, which
      significantly higher than those in CC-CPR group [pH at 20 minutes after
      resuscitation: 7.16 +/- 0.16 vs. 7.01 +/- 0.14; PaO(2): 82.73 +/- 13.20 vs. 58.33
      +/- 17.77; HCO(3)(-): 27.71 +/- 3.11 vs. 21.04 +/- 3.62; BE: -4.78 +/- 4.30 vs. 
      10.23 +/- 2.12; SaO(2): 0.893 +/- 0.088 vs. 0.764 +/- 0.122], and arterial
      partial pressure of carbon dioxide [PaCO(2), mm Hg], K(+) (mmol/L) and lactic
      acid (Lac,mmol/L) were significantly lower than those in CC-CPR group [PaCO(2) at
      20 minutes after resuscitation: 49.40 +/- 15.60 vs. 79.80 +/- 15.35; K(+): 7.18
      +/- 1.76 vs. 8.55 +/- 1.02; Lac: 8.17 +/- 1.46 vs. 10.39 +/- 1.92], with
      statistical significant (P < 0.05 or P < 0.01). But the ROSC rate and 24-hour
      survival rate in ALC-CPR group were significantly higher than those in CC-CPR
      group (ROSC rate: 80.0% vs. 26.7%, P < 0.01; 24-hour survival rate: 60.0% vs.
      13.3%, P < 0.05), and the 24-hour neurological function score was significantly
      lower than that in CC-CPR group (1.11 +/- 0.33 vs. 3.50 +/- 0.70, P < 0.01).
      CONCLUSION: In the incipient stage of cardiopulmonary resuscitation of the swine
      CA model of asphyxia, compared with CC-CPR, ALC-CPR can be more effective.

PMID- 22464580
TI  - [Study of relationship between brain natriuretic peptide levels and heart
      function after open-heart surgery in children with congenital heart disease].
AB  - OBJECTIVE: To investigate significance of plasma brain natriuretic peptide (BNP)
      on evaluation of cardiac function in children with congenital heart disease
      (CHD). METHODS: One hundred and fifty-three children with CHD were
      enrolled.Plasma level of BNP was measured by enzyme linked immunosorbent assay
      (ELISA) at 24 hours after cardiac operation.The left ventricular ejection
      fraction (LVEF) was examined by echocardiogram at the same time. Cardiac index
      (CI) was measured with thoracic impedance method (CI1) and pulse indicator
      continuous cardiac output (PiCCO) system (CI2) at the same time. Correlation
      between BNP, LVEF, CI1 and CI2 was analyzed. The length of mechanical
      ventilation, the length of intensive care unit (ICU) stay, the length of hospital
      stay, and mortality were compared between BNP<140 ng/L group (group A, n = 108)
      and BNP>140 ng/L group (group B, n = 45). RESULTS: The average plasma BNP level
      of 153 children with CHD was (168.8 +/- 71.6) ng/L. The average LVEF was 0.409 +/
      0.137, CI1 was (51.7 +/- 15.0) ml.s(-1).m(-2), and CI2 was (61.7 +/- 11.7) ml.s(
      1).m(-2). Plasma BNP showed negative correlation with CI1 and CI2 [r(1) = -0.79,
      r(2) = -0.79, both P < 0.01]. LVEF showed positive correlation with CI1 and CI2
      [r(1) = 0.68, r(2) = 0.68, both P < 0.01].CI1 showed positive correlation with
      CI2 (r = 0.88, P < 0.01). The length of mechanical ventilation (hours), the
      length of ICU stay (days), and the length of hospital stay (days) in group B were
      significantly longer than those in group A (the length of mechanical ventilation:
      39.7 +/- 11.6 vs. 26.4 +/- 13.5, the length of ICU stay: 4.9 +/- 1.3 vs. 2.5 +/-
      0.9, the length of hospital stay: 15.9 +/- 5.1 vs. 11.2 +/- 3.7, all P < 0.01).
      Mortality of two groups showed no statistical difference. CONCLUSION: Plasma BNP
      was useful for post operative evaluation of cardiac function among the children
      with CHD, and also to predicting the outcome of the patients.

PMID- 22464581
TI  - [Rational control on postoperative blood glucose levels in infants with
      congenital heart disease].
AB  - OBJECTIVE: To investigate optimal level of post-operation blood glucose control
      in infants with congenital heart disease (CHD). METHODS: One hundred and two
      infants <=1 year old undergoing open-heart surgery were randomly divided into
      three groups: intensive blood glucose control group (group A, n = 35), active
      blood glucose control group (group B, n = 38), and common glucose control group
      (group C, n = 29). Insulin injection would be intravenously administrated when
      blood glucose levels up to 8.3, 15.0, and 18.0 mmol/L in group A, B, and C,
      respectively. Blood white blood count (WBC), C-reactive protein (CRP), lactic
      acid, alanine aminotransferase (ALT), creatinine (Cr), incidence of pulmonary
      infection, the length of intensive care unit (ICU) stay, incidence of
      hypoglycemia and mortality were compared at 72 hours after operation among three
      groups. RESULTS: WBC [*10(9)/L], CRP (mg/L) and incidence of pulmonary infection
      in group C were significantly higher than those in group A and group B (WBC: 18.2
      +/- 8.7  vs.  13.2 +/- 5.1, 14.5 +/- 5.7; CRP: 32.9 +/- 10.9  vs.  20.8 +/- 9.8,
      18.6 +/- 8.5; incidence of pulmonary infection: 27.6%  vs.  8.6%, 10.5%, all P <
      0.05), but there were no statistical differences between group A and group B. ALT
      (U/L) in group B was significantly lower than that in group A and group C (49.0
      +/- 17.8  vs.  68.4 +/- 16.9, 69.9 +/- 13.8, both P < 0.05), but there was no
      statistical difference between group A and group C. Incidence of hypoglycemia in
      group A was significantly higher than that in group B and group C (20.0%  vs. 
      2.6%, 3.4%, both P < 0.05), but there was no statistical difference between group
      B and group C. There were no statistical differences in lactic acid (mmol/L), Cr
      (MUmol/L) and the length of ICU stay (days) among group A, B, and C (lactic acid:
      2.1 +/- 0.8, 2.3 +/- 0.5, 2.2 +/- 0.7; Cr: 55.1 +/- 13.4, 49.4 +/- 15.7, 57.3 +/-
      11.6; the length of ICU stay: 3.5 +/- 1.8, 3.2 +/- 1.1, 3.6 +/- 1.6, all P>0.05).
      There was no infant death in three groups. CONCLUSIONS: Severe hyperglycemia
      after open heart operation was associated with increasing WBC count, CRP level
      and incidence of pulmonary infection during the post operative period. However,
      it also demonstrated that intensive blood glucose control be link to increase
      risks of hypoglycemia and liver dysfunction.

PMID- 22464582
TI  - [Analysis of the correlation among plasma brain natriuretic peptide,
      hypersensitive C-reactive protein and left ventricular ejection fraction in
      patients with acute myocardial infarction].

PMID- 22464583
TI  - [A study of QT dispersion in patients with sepsis].

PMID- 22464584
TI  - [Roles of ATP-sensitive potassium pathway in regulating lymphatic function].

PMID- 22464585
TI  - Photodegradation of indigo carmine and methylene blue dyes in aqueous solution by
      SiC-TiO2 catalysts prepared by sol-gel.
AB  - Indigo carmine and methylene blue dyes in aqueous solution were photodegraded
      using SiC-TiO(2) catalysts prepared by sol-gel method. After thermal treatment at
      450 degrees C, SiC-TiO(2) catalysts prepared in this work showed the presence of
      SiC and TiO(2) anatase phase. Those compounds showed specific surface area values
      around 22-25 m(2)g(-1), and energy band gap values close to 3.05 eV. In
      comparison with TiO(2) (P25), SiC-TiO(2) catalysts showed the highest activity
      for indigo carmine and methylene blue degradation, but this activity cannot be
      attributed to the properties above mentioned. Therefore, photocatalytic
      performance is due to the synergy effect between SiC and TiO(2) particles caused
      by the sol-gel method used to prepare the SiC-TiO(2) catalysts. TiO(2)
      nanoparticles are well dispersed onto SiC surface allowing the transfer of
      electronic charges between SiC and TiO(2) semiconductors, which avoid the fast
      recombination of the electron-hole pair during the photocatalytic process.

PMID- 22464586
TI  - Removal of phosphorus by a composite metal oxide adsorbent derived from manganese
      ore tailings.
AB  - The selective adsorption of phosphate (P) from wastewater is a promising method
      for controlling eutrophication in water bodies. In this study, an adsorbent of
      composite metal oxides (CMOMO) was synthesized from manganese ore tailings by the
      process of digestion-oxidation-coprecipitation. CMOMO was characterized using
      several methods, and its adsorption behaviors for phosphate were investigated.
      Based on the results from SEM and BET analysis, CMOMO exhibited a rough surface
      and a large surface area (307.21 m(2)/g). According to the results of EDAX, XRD
      and XPS, its main constituents were determined to be amorphous FeOOH, MnO(2) and
      AlOOH. The kinetic data were best fit using the Elovich model due to its
      complicate composites. The maximal adsorption capacity of P would increase with
      elevated temperatures. Additionally, it was found that the P removal efficiency
      decreased with an increase of pH (4-10) or a decrease of ion strength (1-0.01 M).
      The coexisting anions had little effects on phosphate removal, implying the
      specific adsorption of P by CMOMO. Furthermore, the desorption and reuse results
      indicated that this adsorbent could be regenerated using alkali solutions.

PMID- 22464587
TI  - High-performance porous spherical or octapod-like single-crystalline BiVO4
      photocatalysts for the removal of phenol and methylene blue under visible-light
      illumination.
AB  - Monoclinic BiVO(4) single-crystallites with a polyhedral, spherical or porous
      octapod-like morphology were selectively prepared using the triblock copolymer
      P123 (HO(CH(2)CH(2)O)(20)(CH(2)CH(CH(3))O)(70)(CH(2)CH(2)O)(20)H)-assisted
      hydrothermal method with bismuth nitrate and ammonium metavanadate as metal
      source and various bases as pH adjustor. The BiVO(4) materials were well
      characterized and their photocatalytic activities were evaluated for the removal
      of methylene blue (MB) and phenol in the presence of a small amount of H(2)O(2)
      under visible-light illumination. It is shown that the pH value of the precursor
      solution, surfactant, and hydrothermal temperature had an important impact on
      particle architecture of the BiVO(4) product. The introduction of P123 favored
      the generation of BiVO(4) with porous structures. The BiVO(4) derived
      hydrothermally with P123 at pH 3 or 6 possessed good optical absorption
      performance both in UV- and visible-light regions and hence showed excellent
      photocatalytic activities for the degradation of MB and phenol. It is concluded
      that the high visible-light-driven catalytic performance of the porous octapod
      like BiVO(4) single-crystallites is associated with the higher surface area,
      porous structure, lower band gap energy, and unique particle morphology. Such
      porous BiVO(4) materials are useful in the solar-light-driven photocatalytic
      treatment of organic-containing wastewater.

PMID- 22464588
TI  - The combined effects of UV-B radiation and herbicides on photosynthesis,
      antioxidant enzymes and DNA damage in two bloom-forming cyanobacteria.
AB  - In this study, we investigated the combined effects of UV-B irradiation and
      herbicides (glyphosate, GPS; 2-Methyl-4-chlorophenoxyacetic acid, MCPA-Na; 3-(3,4
      dichlorophenyl)-1,1-dimethylurea, DCMU) and the antioxidant (ascorbic acid, ASC)
      on photosynthesis, antioxidant enzymes and DNA damage in two bloom-forming
      cyanobacteria, Anabaena sp. and Microcystis viridis. UV-B irradiance increased
      reactive oxygen species (ROS) production, which decreased chlorophyll a
      fluorescence yield, pigment content and superoxide dismutase (SOD) activity, and
      increased malondialdehyde (MDA) content and caused serious DNA damage. The degree
      of these damages was aggravated by the addition of DCMU, GPS and MCPA, and was
      partially mitigated by the addition of ASC. During the recovery process, the
      degree and mechanism in restoring DNA damage and photosynthesis inhibition were
      different by the removal of UV-B and herbicides (DCMU, GPS and MCPA) in both
      cyanobacteria. These results suggest that the combination of UV-B and exogenous
      herbicides have detrimental effects on cyanobacterial metabolism through either a
      ROS-mediated process or by affecting the electron transport chain, and may cause
      the shifts in the phytoplankton community.

PMID- 22464589
TI  - Acute exposure to the insecticide O,S-dimethyl phosphoramidothioate
      (methamidophos) leads to impairment of cardiovascular reflexes in rats.
AB  - Poisoning by organophosphorus insecticides is often accompanied by cardiac
      complications which may be serious and even fatal. However, the effects of these
      compounds on the cardiovascular mechanisms involved in blood pressure regulation
      are not known. The aim of this study was to evaluate the effects of a sublethal
      dose (8 mg/kg, i.p.) of the organophosphorus methamidophos on chemoreceptor (CR)
      and Bezold-Jarisch (BJR) cardiovascular reflexes. Male Wistar rats were treated
      with single intraperitoneal injections of methamidophos in saline (n=23) or
      saline (0.9 percent, n=20) and underwent catheterization of femoral artery and
      vein one day after the injections. Cardiovascular recordings were performed 24h
      after the catheterization procedure. Plasma cholinesterase (ChE) activity was
      measured 24h after similar treatments in separate groups (n=10/group). The
      bradycardic component of CR and BJR was significantly attenuated in animals
      treated with methamidophos. The ChE activity was 80 percent reduced in the
      methamidophos-treated animals. Methamidophos impairment of the bradycardic
      component of two important cardiovascular reflexes may contribute to the
      cardiovascular toxicity associated with acute organophosphorus insecticides
      exposure.

PMID- 22464590
TI  - How do patients with rare diseases experience the medical encounter? Exploring
      role behavior and its impact on patient-physician interaction.
AB  - OBJECTIVES: Empirical research shows that patients with severe illnesses prefer
      the physician to dominate decision processes and provide the information needed.
      However, in rare diseases, due to the low prevalence and the lack of expertise,
      the patient is forced to become knowledgeable about his own disease state.
      Objectives of this study were to describe the experiences of patient-physician
      interaction in rare diseases, to develop an empirically derived typology of
      interaction patterns and to explore the antecedents of these interaction
      patterns, with a special focus on role behavior. Building on these results,
      implications for health care policy are made. METHODS: We designed an exploratory
      study as a series of semi-standardized interviews with patients suffering from
      rare diseases. We extracted the following six rare diseases: amyotrophic lateral
      sclerosis, Duchenne muscular dystrophy, epidermolysis bullosa, Marfan syndrome,
      neurodegeneration with brain iron accumulation and Wilson's disease. A total of
      107 interviews were recorded, transcribed and analyzed thematically in accordance
      with the grounded theory tradition. RESULTS: As suggested, insufficient expertise
      of the healthcare providers proved to be a major problem in the highly
      specialized treatment process of rare diseases. Here, the patient often becomes
      an expert in his disease. Therefore, we identified the patient-directed
      interaction as a widely experienced communication pattern among patients with
      rare diseases. Our study also showed that role discrepancies have a major impact
      on communication processes in this context. CONCLUSIONS: People with rare
      diseases often face challenges, due to the low prevalence and the resulting lack
      of knowledge of their healthcare providers. Communication processes in this
      context are mainly affected by the role behavior of both the patient and
      provider. The present study showed the relevance of the provider's ability to
      acknowledge the active role of the patient as an informed, involved and
      interactive partner in the treatment process. However, allowing the patient to
      control therapy may require a change of mind-set with some long-standing
      traditional roles in healthcare.

PMID- 22464591
TI  - (De)centralization of social support in six Western European countries.
AB  - INTRODUCTION: Participation of disabled or chronically ill persons into the
      society may require support in the sense of human or technical aid. In this study
      we look into the decision making power of governments and the way citizens are
      involved in these processes. Decision making power can be political, financial
      and administrative and may be organized at national, regional or local level.
      METHODS: This is a cross-sectional descriptive study of the decision making power
      in Belgium, France, Germany, the Netherlands, Sweden and the United Kingdom in
      2010. We focused on acts and regulations for human and technical aids and for
      making the environment accessible. RESULTS: Several acts and regulations were
      identified in relation to social support. In the Netherlands and Sweden social
      support was mainly organized in one act, whereas in the other countries social
      support was part of several acts or regulations. Citizen's voice appeared to be
      represented in boards or advisory committees. Descriptions of entitlements varied
      from explicitly formulated to globally described. CONCLUSIONS: The level of
      decision making power varies between the countries en between the types of
      decision making power. Citizens' participation is mainly represented through
      patient associations. Countries with strongly decentralized decision making make
      use of framework legislation at national level to set general targets or aims.

PMID- 22464593
TI  - Intraperitoneal delivery of paclitaxel with injectable hydrogel: "seeing" is not
      always "believing".

PMID- 22464592
TI  - Bilingualism: consequences for mind and brain.
AB  - Building on earlier evidence showing a beneficial effect of bilingualism on
      children's cognitive development, we review recent studies using both behavioral
      and neuroimaging methods to examine the effects of bilingualism on cognition in
      adulthood and explore possible mechanisms for these effects. This research shows
      that bilingualism has a somewhat muted effect in adulthood but a larger role in
      older age, protecting against cognitive decline, a concept known as 'cognitive
      reserve'. We discuss recent evidence that bilingualism is associated with a delay
      in the onset of symptoms of dementia. Cognitive reserve is a crucial research
      area in the context of an aging population; the possibility that bilingualism
      contributes to cognitive reserve is therefore of growing importance as
      populations become increasingly diverse.

PMID- 22464594
TI  - Staged management of a primary aortobronchial fistula: a novel approach using a
      trapezius flap repair.
AB  - There have been few reported cases of management of an aortobronchial fistula. We
      describe the case of a 68 year-old male with a very high operative risk who had a
      successful staged management of a primary aortobronchial fistula. An endovascular
      stent was placed initially, however due to recurrence of the fistula a second
      stent was deployed within the first one some three months after. Fifteen months
      later he represented with massive haemoptysis, severe cachexia and at this stage
      the best course of surgical management was thought to be lobectomy via
      thoracotomy followed by trapezius flap overlay covering the exposed stent and
      separating it from the remaining lung.

PMID- 22464595
TI  - Radiofrequency ablation for atrial tachycardia and atrial flutter.
AB  - Atrial tachycardia is a generic term for a range of tachyarrhythmias with their
      origin in the atria. These can be broadly divided by mechanism into macro
      reentrant, focal and small circuit re-entry. "Atrial flutter" is a term which,
      today, should be restricted to those classical circuits around the tricuspid
      annulus dependent on the cavo-tricuspid isthmus. The advent of sophisticated
      mapping solutions has rendered the vast majority of these atrial circuits curable
      with catheter ablation, with high success rates and very low incidence of
      complications.

PMID- 22464596
TI  - Inhibiting host-pathogen interactions using membrane-based nanostructures.
AB  - Virulent strains of bacteria and viruses recognize host cells by their plasma
      membrane receptors and often exploit the native translocation machinery to invade
      the cell. A promising therapeutic concept for early interruption of pathogen
      infection is to subvert this pathogenic trickery using exogenously introduced
      decoys that present high-affinity mimics of cellular receptors. This review
      highlights emerging applications of molecularly engineered lipid-bilayer-based
      nanostructures, namely (i) functionalized liposomes, (ii) supported colloidal
      bilayers or protocells and (iii) reconstituted lipoproteins, which display
      functional cellular receptors in optimized conformational and aggregative states.
      These decoys outcompete host cell receptors by preferentially binding to and
      neutralizing virulence factors of both bacteria and viruses, thereby promising a
      new approach to antipathogenic therapy.

PMID- 22464597
TI  - Phenotypic and histologic characteristics of cutaneous melanoma in patients with
      melanocortin-1 receptor polymorphisms.
AB  - BACKGROUND: The melanocortin-1 receptor (MC1R) is an important risk factor for
      melanoma due to its role in the production of melanin in response to sun
      exposure. OBJECTIVES: To analyze the phenotypic and histologic characteristics of
      cutaneous melanoma in patients carrying mutations in MC1R and assess the
      influence of sun exposure on the occurrence of melanoma. MATERIAL AND METHODS: A
      total of 224 patients with a diagnosis of melanoma seen in the Department of
      Dermatology at Hospital General Universitario Gregorio Maranon in Madrid, Spain
      between September 2004 and December 2009 were included in the study. The genomic
      sequence of MC1R was analyzed by polymerase chain reaction. RESULTS: At least one
      of the following MC1R variants was present in 58% of the patients: V60L, V92M,
      I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of
      sunburn (P=.018) and melanomas located on areas with intermittent sun exposure
      (P=.019), and the majority had a diagnosis of superficial spreading melanoma.
      These associations were especially significant in patients with the R160W and
      D294H variants. Carriers of R160W also had melanomas associated with melanocytic
      nevi (P=.028). CONCLUSIONS: The results of our study suggest that there may be a
      relationship between the expression of certain MC1R variants and sun exposure,
      history of sunburn, and skin type. They also indicate a higher frequency of
      superficial spreading melanomas and melanomas associated with melanocytic nevi in
      patients carrying certain mutations in MC1R.

PMID- 22464598
TI  - Mycobacterium chelonae infection in a patient being treated with adalimumab.

PMID- 22464599
TI  - Skin bioengineering: preclinical and clinical applications.
AB  - Regenerative Medicine is an emerging field that combines basic research and
      clinical observations in order to identify the elements required to replace
      damaged tissues and organs in vivo and to stimulate the body's intrinsic
      regenerative capacity. Great benefits are expected in this field as researchers
      take advantage of the potential regenerative properties of both embryonic and
      adult stem cells, and more recently, of induced pluripotent stem cells.
      Bioengineered skin emerged mainly in response to a critical need for early
      permanent coverage of extensive burns. Later this technology was also applied to
      the treatment of chronic ulcers. Our group has established a humanized mouse
      model of skin grafting that involves the use of bioengineered human skin in
      immunodeficient mice. This model is suitable for the study of physiologic and
      pathologic cutaneous processes and the evaluation of treatment strategies for
      skin diseases, including protocols for gene and cell therapy and tissue
      engineering.

PMID- 22464600
TI  - Clipping vs. coiling in acute aneurysmal subarachnoid haemorrhage: Should the
      patient's medical condition influence treatment modality?
AB  - INTRODUCTION: Acute subarachnoid haemorrhage (SAH) resulting from aneurysmal
      rupture is a medical condition associated with significant morbidity and
      mortality. Medical complications resulting from the bleeding itself, along with
      the patient's underlying medical conditions are known to represent possible
      prognostic factors in acute SAH. However, their respective significance on the
      patient's overall clinical outcome following either endovascular coiling (EC) or
      surgical clipping (SC) remains to be ascertained as well as their potential role
      in choosing a definitive treatment option. We thus reviewed the evidence
      concerning the patient's medical condition as a factor in this decision making
      process. METHODOLOGY: Source data were obtained from a MEDLINE search of the
      medical literature and by manual review of published randomised trials comparing
      EC to SC. RESULTS: The last three decades allowed for detection of medical
      complications with increasing frequency in the context of SAH, as awareness for
      them has improved. Despite the fact that a patient's extra-neurological condition
      can be a significant prognostic factor after a SAH, our review demonstrates that
      medical conditions in general were not taken into consideration in randomized
      trials comparing EC to SC. Also, we found no analysis comparing the potential
      role of prior versus post-SAH medical conditions in choosing either therapeutic
      avenue. CONCLUSION: It is not determined whether it is appropriate for SAH
      patients to be offered treatment for a ruptured aneurysm based mostly on
      anatomical criteria or if, within certain subgroups of patients, EC and SC should
      also be recommended in light of what the patient can tolerate from a medical
      standpoint. Although we hypothesize that in practice, the patient's medical
      condition is considered in the decision making process, it remains to be
      documented. Patient, aneurysm and institution-related factors are all
      interrelated, as is patient care. Data on all of these factors are thus needed
      and their analysis by association rather than by dissociation may be the key in
      answering our question.

PMID- 22464602
TI  - [Cerebrospinal fluid rhinorrhea following endocopic trans-sphenoidal pituitary
      surgery: Experience from 337 patients].
AB  - INTRODUCTION: Cerebrospinal fluid (CSF) leak is a frequent complication after
      trans-sphenoidal pituitary surgery. We try to determine the incidence, risk
      factors, diagnostic procedures, and management of CSF leaks following trans
      sphenoidal pituitary macroadenoma surgery. METHODS: A retrospective analysis of
      337 patients data. RESULTS: Postoperative CSF leaks occurred in 11 patients
      (3,1%). Ten patients had to be reoperated. Three patients had meningitis.
      Intraoperative CSF leak is the only significant predictive factor of
      postoperative CSF leak. Revision surgery, wide opening of the sella turcica and
      insufficient reconstruction of the sellar floor also seem to play a role (for six
      cases of postoperative CSF leak, the closure material had been excluded).
      CONCLUSION: Prevention of the postoperative CSF leak needs screening of intra
      operative CSF leak. The strength of the sellar floor is essential in order to
      avoid the ejection of the closure material, related to the intracranial pression.

PMID- 22464603
TI  - [Cerebral atypical rhabdoid/teratoid tumor: report of two cases].
AB  - The cerebral atypical rhabdoid/teratoid tumor constitutes one of the most
      aggressive tumors of children. Such tumors are equally characterized by a
      critically and speedly mortal development. The optimal management of such tumors
      remains unknown. The authors report two cases of cerebral atypical rhabdoid
      teratoid tumor in 8- and 10-year girls and discuss the histological features,
      immunochemistry study, prognosis and treatment of these rare tumors.

PMID- 22464605
TI  - Cost-benefit analysis of a socio-technical intervention in a Brazilian footwear
      company.
AB  - This article presents a costs-benefits analysis of a macroergonomic intervention
      in a Brazilian footwear company. Comparing results of a pilot line (composed by
      100 multiskilled workers organized in teams) with eight traditional lines (still
      working in a one human being/one task model) the intervention showed to be worth
      pursuing since achieved gains were higher than intervention costs: there was a
      reduction in human resource costs (80% reduction in industrial accidents, 100%
      reduction in work-related musculoskeletal disorders or WMSD, medical
      consultations and turnover, and a 45.65% reduction in absenteeism) and production
      improvement (productivity increased in 3% and production waste decrease to less
      than 1%). The net intervention value of the intervention was around U$ 430,000
      with a benefit-to-cost ratio of 7.2. Moreover, employees who worked in the pilot
      line understood that their quality of work life improved, compensating the
      anxiety brought up by the radical changes implemented.

PMID- 22464604
TI  - [Surgical complications of deep brain stimulation: clinical experience of 184
      cases].
AB  - BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) is an effective treatment of
      movement disorders and psychiatric diseases. However, this surgery is still time
      consuming and associated with complications, among which we aimed to identify non
      stimulo-induced adverse effects. Hence, we retrospectively systematically
      analyzed patients operated on, at our institution, using magnetic resonance
      imaging (MRI) direct anatomic mapping. METHODS: One hundred and seventy-five
      patients (184 surgeries) were performed between 1994 and 2008, for Parkinson's
      disease, essential tremor, dystonia and obsessive compulsive disorder. Primary
      anatomic targets were the subthalamic region, the intern pallidum and the
      thalamus. Final electrode positioning was adjusted according to intraoperative
      neuron recordings and acute stimulation tests. All surgically related adverse
      effects were collected. Life threatening or new non-planed surgery was considered
      as severe adverse effects. RESULTS: Adverse effects occurred 10 times (5.4%)
      during MRI acquisition, 24 times (13%) with five serious (2.7%) including one1
      death (0.5%) during electrodes implantation and 17 times (9.2%) with four serious
      (2.2%) during neuropacemaker implantation. Electrodes were repositioned in six
      cases (five patients, n=3.4%). CONCLUSION: DBS efficiency is recognized however
      the significant incidence of adverse effects should prompt us to improve the
      procedures.

PMID- 22464606
TI  - A case of pressure ulceration and associated haemorrhage in a patient using a
      faecal management system.
AB  - Diarrhoea is a difficult patient problem to manage in the intensive care setting,
      causing odour, discomfort and embarrassment for the patient and potential for
      loss of skin integrity and cross contamination. Caring for these patients is
      resource-intensive. A recently developed product for the management of faecal
      incontinence is the Flexi-Seal Faecal Management System (FMS((c))). Whilst this
      product is usually effective for managing diarrhoea, there are uncommon but
      serious complications associated with its use. Rectal bleeding attributed to
      pressure ulceration of the rectal mucosa can be severe, especially in conjunction
      with the use of anticoagulation. We report a case of severe rectal bleeding
      requiring surgical intervention and administration of large amounts of blood
      products, caused by pressure ulceration as a result of the use of a Flexi-Seal
      FMS((c)). The case report is followed by a review of the literature. Similar
      complications have been described by others. Although, based on the number of
      reported complications, the incidence of serious complications appears to be low,
      a publication bias cannot be ruled out. Knowledge of the complications associated
      with the device is important for evaluating the appropriateness of insertion and
      for ensuring the safe and effective on going care of patients using Flexi-Seal
      FMS((c)).

PMID- 22464607
TI  - Correlational analysis.
AB  - A common question of interest in nursing research is the relationships between
      variables. Correlational analysis is a statistical technique employed to
      investigate the magnitude and significance of such relationships. This paper
      presents commonly used techniques to examine bivariate relationships of
      interval/ratio, ordinal and nominal variables.

PMID- 22464608
TI  - Just another chest pain in the emergency department?

PMID- 22464609
TI  - Clinical experience does not correlate with the perceived need for
      cardiopulmonary resuscitation training.
AB  - BACKGROUND: The efficiency of cardiopulmonary resuscitation (CPR) training is
      dependent upon different influencing factors, such as the presented concepts, the
      participants' willingness to learn, and the interval between training sessions.
      However, the optimal interval for refreshing CPR training is less clear.
      OBJECTIVE: We evaluated the perceived need of simulator-based CPR training for
      nurses and correlated it with their clinical experience. METHODS: The 60 invited
      nurses were trained in simulator-based CPR. Knowledge about adult advanced life
      support was evaluated using a questionnaire after training, and participants
      rated their desired individual frequency of simulator-based training as well as
      the value of the presented training using a six-point Likert scale. The same
      questions were asked again after 1 year. RESULTS: All participants agreed about
      the usefulness of this type of simulator-based training. The average number of
      correct answers about typical facts in adult advanced life support showed an
      almost bell-shaped distribution, with the highest point at 6-15 years of clinical
      experience and the lowest points at<=5 and>=21 years. The desired training
      frequency need was inversely correlated with clinical experience. CONCLUSIONS:
      There is a high interest in CPR training among nursing staff. Self-assessment
      about the training-frequency need was inversely correlated with clinical
      experience. However, the average number of correct answers on resuscitation
      questions decreased with clinical experience. Therefore, the training
      effectiveness seems to be extremely dependent on clinical experience, and
      therefore, training experienced senior nurses might be more challenging than
      training novice nurses.

PMID- 22464610
TI  - The effects of resident level of training on the rate of pediatric prescription
      errors in an academic emergency department.
AB  - BACKGROUND: Medication errors are a leading cause of increased cost and
      iatrogenic injury in the pediatric population. In the academic setting, studies
      have suggested that these increased error rates are related primarily to resident
      inexperience, thus advocating a higher level of supervision. STUDY OBJECTIVE: We
      sought to identify the number of prescription errors in our institution's
      academic Emergency Department, how this varied between the beginning and end of
      the academic year and between practitioners at varying levels of training.
      METHODS: A retrospective review of computer-based outpatient prescriptions for
      children aged 0-12 years old was performed. Outpatient prescriptions were
      reviewed during a 2-week time block at the end of the academic year and beginning
      of the academic year (109 [June] and 111 [July] data sets, respectively).
      Prescriptions were retrieved electronically and reviewed for appropriate dosing.
      Errors were defined as those that varied>10% above or below recommended weight
      based dosing. RESULTS: Twenty-nine (16.1%) of 180 written prescription orders
      were determined to be incorrectly written. Error rates were not significantly
      different between the beginning and end of the academic year. In both sampling
      periods, a higher percentage were found to be derived from senior level
      practitioners in both data sets (9/14 and 10/15; respectively), but few of these
      were considered high-grade prescription errors. CONCLUSIONS: Overall prescription
      error rates at our institution are comparable to nationally reported error rates
      in children. Error rates were not associated with newly matriculated residents.
      These findings dispute previously held opinion that physician level of training
      is a factor of prescription errors.

PMID- 22464611
TI  - Juvenile first rib fracture caused by morning stretching.
AB  - BACKGROUND: First rib fractures are very rare, being primarily associated with
      external blunt trauma. Related conditions, such as sudden contraction of the neck
      muscle, stress fractures, and fatigue fractures, have been reported sporadically.
      These fractures are mostly related to repetitive or explosive physical training.
      However, anatomical relationships and related injury mechanisms may cause first
      rib fractures without repetitive sports activity. OBJECTIVE: To present a case of
      juvenile first rib fracture caused by morning stretching without sports activity.
      CASE  REPORT: We present a rare case report of juvenile atraumatic first rib
      fracture. CONCLUSION: Physicians should be aware that even morning stretching
      with yawning can cause a first rib fracture in children. Awareness is important
      for early recognition, and proper management is critical for a pain-free return
      to normal life. An understanding of the mechanism of atraumatic first rib
      fracture is important.

PMID- 22464613
TI  - Primary extranodal non-Hodgkin's lymphoma involving masseter and buccinator
      muscles.
AB  - Extranodal lymphoma of the head and neck comprises a heterogeneous group of
      tumours with different histological types, modes of presentation and prognosis.
      Lymphomatous involvement of skeletal muscles and particularly muscles of
      mastication and facial expression is extremely rare, but primary muscle lymphoma
      should be considered in the differential diagnosis of muscle masses. This article
      highlights clinical, radiological and histopathological findings of primary
      extranodal non-Hodgkin's lymphoma involving masseter and buccinator muscles in an
      immunocompetent patient.

PMID- 22464612
TI  - Ambulance diversion reduction and elimination: the 3-2-1 plan.
AB  - BACKGROUND: The diversion of ambulances from their intended emergency departments
      (EDs) occurs frequently, compromising patient care. Previously, we reduced
      ambulance diversion (AD) by 74% in a large urban area with 17 EDs. OBJECTIVES: In
      this follow-up program, we sought to further reduce and eliminate AD by
      progressively reducing the duration of each AD event. METHODS: Using tight
      diversion criteria, AD at each ED was limited by protocol to 3h at a stretch,
      after which incoming ambulances had to be accepted at that ED for at least 1h.
      After 6 months, AD was limited to 2h per diversion event; after another 6 months,
      AD was limited to 1h. The monitoring for AD was programmed into a region-wide,
      Internet-based Emergency Medical Services (EMS) program. RESULTS: Total annual AD
      decreased from 8469 h in 2006 (pre-implementation) to 4592 h in 2007 (during
      implementation), and finally to 2439 h and 2306 h in 2008 and 2009 (post
      implementation), respectively, an 87.4% (95% confidence interval 64.6-95.5%)
      reduction, and one county within the region eliminated AD altogether. From 2006
      to 2009, overall increases were noted in EMS arrivals (7.8%), ED census (13.0%),
      hospital admissions (6.6%), Intensive Care Unit admissions (17.1%), and overall
      Sacramento population (1.9%). CONCLUSIONS: By limiting the duration of AD events
      to progressively shorter periods of time using a region-wide, Internet-based EMS
      program, we reduced AD hours in 17 EDs by 87.4% and eliminated AD in one entire
      county. This original, collaborative 3-2-1 Plan may be readily reproduced across
      the country to progressively reduce and eliminate AD.

PMID- 22464614
TI  - Beginning a year of collaboration.

PMID- 22464615
TI  - Innovative educators.

PMID- 22464617
TI  - Implementation of an intraoperative clinical experience for senior level
      baccalaureate nursing students.
AB  - Perioperative nursing is a specialty that has been eliminated from many nursing
      education programs. With the loss of perioperative clinical experiences, the
      number of students pursuing a career in perioperative nursing after graduation
      has declined. A faculty member at one Midwestern school of nursing developed and
      implemented a perioperative clinical experience for senior-level baccalaureate
      nursing students in a critical care nursing course. This program, developed with
      the assistance of four local hospitals and the college of nursing, included an
      eight-hour OR orientation and 56 clinical hours. Students were placed in the OR
      under preceptor guidance and supervision. Feedback from evaluations was positive
      and provided recommendations for improving the program, in particular, to allow
      more clinical hours and more hands-on experience for the students.

PMID- 22464618
TI  - Redesigning OR orientation.
AB  - The nursing shortage triggered by retiring nurses is expected to affect all areas
      of nursing but particularly specialized nursing areas, such as perioperative
      units. In addition, the perioperative environment is a difficult place for novice
      nurses to fit in. Many factors contribute to making the OR environment stressful,
      and novice nurses often feel the effects of not being readily accepted into the
      social culture of the OR. Leaders in the OR department of a busy trauma center
      with a large number vacancies, an inability to recruit experienced perioperative
      nurses, and difficulty retaining new nurses redesigned the orientation process
      with the intent of recruiting high quality RNs, improving the nurse retention
      rate after orientation, and making the perioperative area a positive learning
      environment. The new process is a consistent, structured program that includes
      AORN's Periop 101: A Core Curriculum, dedicated preceptors, daily feedback and
      goals for orientees, regular meetings for new staff members, and increased
      inclusion of existing staff members.

PMID- 22464619
TI  - Developing a perioperative educational video web site.
AB  - Nurses frequently have to adjust to changes in technology, particularly in the
      OR, but cataloging the wealth of resources commonly used in the OR (eg,
      equipment, supplies, how to use them) has not kept pace. To address this, I
      worked with the information systems administrative coordinator at the University
      of Texas Medical Branch, Galveston, to design and implement a perioperative
      intranet site that includes videos and fact sheets about equipment and supplies
      and that can be accessed by all perioperative staff members. This required
      promoting the idea and getting stakeholder sign-on, soliciting videotapes and
      DVDs and screening all submissions for appropriateness, choosing and formatting
      applicable resources for use on the site, working with members of the information
      systems department to create a web site after the video library was assembled,
      and helping staff members use and accept the site as a valuable educational
      resource. This intranet web site has been available to staff members for two
      years, and data from a recent survey of staff members and from mandatory intranet
      inservice compliance programs show evidence of its effectiveness.

PMID- 22464620
TI  - Using YouTube in perioperative nursing education.
AB  - Educators today need innovative teaching strategies to meet the learning needs of
      the multigenerational population of perioperative nurses. Emerging technologies,
      such as YouTube, the world's largest video-sharing web site, can be used as a
      component of an active learning strategy that can appeal to a broad group of
      nurses along the novice-to-expert proficiency continuum. Using video clips can be
      a useful method to engage learners and promote critical thinking, decision
      making, and creativity. YouTube videos can be used to teach skills or as a
      platform for discussion. Learners also can create and upload their own videos to
      educate others. Increased engagement and active learning can lead the
      perioperative nurse to a deeper understanding of the educational material.

PMID- 22464621
TI  - Educating for the future.
AB  - The current lack of perioperative clinical rotations in nursing schools makes it
      imperative that perioperative nurses create ways to entice the next generation of
      nurses to work in the OR. At Danbury Hospital, Danbury, Connecticut, the OR
      manager and clinical educators looked at the challenges that nursing students
      face in the perioperative clinical setting and created an orientation to help to
      ease their fears about observing in the OR, familiarize them with the
      perioperative nursing role, and perhaps encourage more nursing students to
      consider perioperative nursing as a career. We used the "AORN guidance statement:
      The value of clinical learning activities in the perioperative setting in
      undergraduate nursing curricula" as a framework for a perioperative orientation
      class that addresses the challenges and meets the students' academic goals. We
      also used the nursing curriculum objectives from Western Connecticut State
      University, Danbury, to plan the students' clinical experience in surgery. Our
      approach has attracted more student interest in perioperative nursing than in
      previous years, resulting in more students requesting a perioperative clinical
      rotation or senior practicum.

PMID- 22464622
TI  - Implementing AORN recommended practices for hand hygiene.
AB  - This article focuses on implementing the revised AORN "Recommended practices for
      hand hygiene in the perioperative setting." The content of the document has been
      expanded and reorganized from the previous iteration and now includes specific
      activity statements about water temperature, water and soap dispensing controls,
      the type of dispensers to use, paper towel dispenser requirements, placement of
      soap and rub dispensers, and regulatory requirements for products and
      recommendations for hand hygiene practices. A successful hand hygiene program
      allows end users to have input into the selection and evaluation of products and
      should include educating personnel about proper hand hygiene, product composition
      and safety, and how and when to use specific products. Measures for competency
      evaluation and compliance monitoring include observations, quizzes, skills labs,
      electronic monitoring systems, handheld device applications, and data collection
      forms.

PMID- 22464623
TI  - Anticoagulation management in the ambulatory surgical setting.
AB  - Many people receiving maintenance anticoagulation therapy require surgery each
      year in ambulatory surgery centers. National safety organizations focus attention
      toward improving anticoagulation management, and the American College of Chest
      Physicians has established guidelines for appropriate anticoagulation management
      to balance the risk of thromboembolism when warfarin is discontinued with the
      risk of bleeding when anticoagulation therapy is maintained. The guidelines
      recommend that patients at high or moderate risk for thromboembolism should be
      bridged with subcutaneous low-molecular-weight heparin or IV unfractionated
      heparin with the interruption of warfarin, and low-risk patients may require
      subcutaneous low-molecular-weight heparin or no bridging with the interruption of
      warfarin. The guidelines recommend the continuation of warfarin for patients who
      are undergoing minor dermatologic or dental procedures or cataract removal. The
      literature reveals, however, that there is not adequate adherence to these
      recommendations and guidelines. Management of anticoagulation therapy by a nurse
      practitioner may improve compliance and safety in ambulatory surgery centers.

PMID- 22464624
TI  - User interfaces in the OR.

PMID- 22464625
TI  - Patients without borders: the rise of surgical tourism.

PMID- 22464626
TI  - Incivility in nursing: unsafe nurse, unsafe patients.

PMID- 22464630
TI  - Responsibilities of nursing schools with regard to peer mentoring.
AB  - This article reports on the postgraduate critical care students' mentoring of the
      third-year undergraduate nursing students during integrated work-based learning
      in the critical care units. The purpose of the research was to describe what the
      nursing school could do to improve this mentoring programme. A qualitative
      descriptive design was used. The nominal group technique was used to gather data
      from the mentors and mentees. Data from the groups were combined and
      qualitatively analysed into themes. Thereafter the themes were quantitatively
      ranked. The themes, ranking from the highest to the lowest, were orientation,
      organisation, mentoring process, characteristics of the mentor, and feedback to
      the mentor. Findings suggest that the nursing school does not always optimally
      support the mentoring programme. It is recommended that more than one
      communication medium be used to disperse information among role-players. Nursing
      schools should develop mentors, monitor their interactions with mentees and give
      them feedback on their mentoring skills. It is also the responsibility of the
      nursing school to select mentors that match the desired profile of mentors. 

PMID- 22464629
TI  - Organ-specific exposure and response to sulforaphane, a key chemopreventive
      ingredient in broccoli: implications for cancer prevention.
AB  - Naturally occurring sulforaphane (SF) has been extensively studied for cancer
      prevention. However, little is known as to which organs may be most affected by
      this agent, which impedes its further development. In the present study, SF was
      administered to rats orally either in a single dose or once daily for 7 d. Tissue
      distribution of SF was measured by a HPLC-based method. Glutathione S-transferase
      (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two well-known cytoprotective
      phase 2 enzymes, were measured using biochemical assays to assess tissue response
      to SF. SF was delivered to different organs in vastly different concentrations.
      Tissue uptake of SF was the greatest in the stomach, declining rapidly in the
      descending gastro-intestinal tract. SF was rapidly eliminated through urinary
      excretion, and urinary concentrations of SF equivalents were 2-4 orders of
      magnitude higher than those of plasma. Indeed, tissue uptake level of SF in the
      bladder was second only to that in the stomach. Tissue levels of SF in the colon,
      prostate and several other organs were very low, compared to those in the bladder
      and stomach. Moreover, induction levels of GST and NQO1 varied by 3- to 6-fold
      among the organs of SF-treated rats, though not strictly correlated with tissue
      exposure to SF. Thus, there is profound organ specificity in tissue exposure and
      response to dietary SF, suggesting that the potential chemopreventive benefit of
      dietary SF may differ significantly among organs. These findings may provide a
      basis for prioritising organs for further chemopreventive study of SF.

PMID- 22464631
TI  - Perceived knowledge and clinical comfort with genetics among Taiwanese nurses
      enrolled in a RN-to-BSN program.
AB  - BACKGROUND: Advances in genetics have had a profound impact on health care. Yet,
      many nurses, as well as other health care providers, have limited genetic
      knowledge and feel uncomfortable integrating genetics into their practice. Very
      little is known about perceived genetic knowledge and clinical comfort among
      Taiwanese nurses enrolled in a Registered Nurse to Bachelor of Science in Nursing
      program. OBJECTIVES: To examine perceived knowledge and clinical comfort with
      genetics among Taiwanese nurses enrolled in a Registered Nurse to Bachelor of
      Science in Nursing program and to assess how genetics has been integrated into
      their past and current nursing programs. The study also sought to examine
      correlations among perceived knowledge, integration of genetics into the nursing
      curriculum, and clinical comfort with genetics. DESIGN: A descriptive, cross
      sectional study. SETTINGS: Taiwanese nurses enrolled in a Registered Nurse to
      Bachelor of Science in Nursing program were recruited. METHODS: A total of 190 of
      220 nurses returned the completed survey (86.36% response rate). Descriptive
      statistics and the Pearson product-moment correlation were used for data
      analysis. RESULTS: Most nurses indicated limited perceived knowledge and clinical
      comfort with genetics. Curricular hours focused on genetics in a current nursing
      program were greater than those in past nursing programs. The use of genetic
      materials, attendance at genetic workshops and conferences, and clinically
      relevant genetics in nursing practice significantly related with perceived
      knowledge and clinical comfort with genetics. However, there were no correlations
      between prior genetic-based health care, perceived knowledge, and clinical
      comfort with genetics. CONCLUSIONS: This study demonstrated the need for
      emphasizing genetic education and practice to ensure health-related professionals
      become knowledgeable about genetic information. Given the rapidly developing
      genetic revolution, nurses and other health care providers need to utilize
      genetic discoveries to optimize health outcomes.

PMID- 22464632
TI  - Untangling a complex issue: an overview of initiatives to support nursing and
      midwifery student recruitment, selection and retention in Scottish Universities.
AB  - The reasons behind attrition rates in nursing and midwifery are many and complex.
      However, of the four UK countries, Scotland has been consistently cited as having
      the highest attrition rate from its pre-registration nursing and midwifery
      education programmes. This paper provides an overview of a nationally coordinated
      programme of work to support evidence-based intervention and identifies both
      opportunities for further national and international initiatives and presents
      early indicators of improvement in retention and completion.

PMID- 22464633
TI  - The negative influence of significant others on high academic achieving school
      pupils' choice of nursing as a career.
AB  - The International Council of Nurses proposes that the shortage of nurses is
      global in scale and is expected to become much worse in the years ahead. A major
      factor impacting on the worldwide nursing shortage is the diminishing number of
      young people choosing nursing as a career (International Council of Nurses,
      2008). One important dimension of the school pupils' career choice process is
      their interactions with significant others and the influence of these significant
      others (Hodkinson and Sparkes, 1997). As Schools/Departments of Nursing endeavour
      to attract more intellectual school leavers it is important to examine what
      advice and opinions are significant others giving regarding nursing as a career
      choice and how influential is this advice. This paper is based on interview data
      from 20 high academic achieving 5th and 6th year school pupils in Scotland,
      paradigmatic cases from a larger sample, who had considered nursing as a possible
      career choice within their career preference cluster, but then later disregarded
      nursing and decided to pursue medicine or another health care profession. The
      data was particularly striking in revealing the negative influence of significant
      others on high academic achieving school pupils' choice of nursing as a career.
      The influence of significant others, these being specifically parents, guardians,
      guidance teachers and career advisors was very apparent in the data in that they
      had a very negative view regarding nursing as a career choice for high academic
      achieving school pupils.

PMID- 22464634
TI  - Influence of real and virtual heights on standing balance.
AB  - Fear and anxiety induced by threatening scenarios, such as standing on elevated
      surfaces, have been shown to influence postural control in young adults. There is
      also a need to understand how postural threat influences postural control in
      populations with balance deficits and risk of falls. However, safety and
      feasibility issues limit opportunities to place such populations in physically
      threatening scenarios. Virtual reality (VR) has successfully been used to
      simulate threatening environments, although it is unclear whether the same
      postural changes can be elicited by changes in virtual and real threat
      conditions. Therefore, the purpose of this study was to compare the effects of
      real and virtual heights on changes to standing postural control, electrodermal
      activity (EDA) and psycho-social state. Seventeen subjects stood at low and high
      heights in both real and virtual environments matched in scale and visual detail.
      A repeated measures ANOVA revealed increases with height, independent of visual
      environment, in EDA, anxiety, fear, and center of pressure (COP) frequency, and
      decreases with height in perceived stability, balance confidence and COP
      amplitude. Interaction effects were seen for fear and COP mean position; where
      real elicited larger changes with height than VR. This study demonstrates the
      utility of VR, as simulated heights resulted in changes to postural, autonomic
      and psycho-social measures similar to those seen at real heights. As a result, VR
      may be a useful tool for studying threat related changes in postural control in
      populations at risk of falls, and to screen and rehabilitate balance deficits
      associated with fear and anxiety.

PMID- 22464635
TI  - Speeding up or slowing down?: Gait adaptations to preserve gait stability in
      response to balance perturbations.
AB  - It has frequently been proposed that lowering walking speed is a strategy to
      enhance gait stability and to decrease the probability of falling. However,
      previous studies have not been able to establish a clear relation between walking
      speed and gait stability. We investigated whether people do indeed lower walking
      speed when gait stability is challenged, and whether this reduces the probability
      of falling. Nine healthy subjects walked on the Computer Assisted Rehabilitation
      ENvironment (CAREN) system, while quasi-random medio-lateral translations of the
      walking surface were imposed at four different intensities. A self-paced
      treadmill setting allowed subjects to regulate their walking speed throughout the
      trials. Walking speed, step length, step frequency, step width, local dynamic
      stability (LDS), and margins of stability (MoS) were measured. Subjects did not
      change walking speed in response to the balance perturbations (p=0.118), but made
      shorter, faster, and wider steps (p<0.01) with increasing perturbation intensity.
      Subjects became locally less stable in response to the perturbations (p<0.01),
      but increased their MoS in medio-lateral (p<0.01) and backward (p<0.01)
      direction. In conclusion, not a lower walking speed, but a combination of
      decreased step length and increased step frequency and step width seems to be the
      strategy of choice to cope with medio-lateral balance perturbations, which
      increases MoS and thus decreases the risk of falling.

PMID- 22464636
TI  - Catch! Movement kinematics of two-handed catching in boys with Developmental
      Coordination Disorder.
AB  - PURPOSE: To quantify two-handed catching in boys with Developmental Coordination
      Disorder (DCD) by examining sequencing of the upper limb and trunk segments, and
      degree of symmetry. METHOD: Thirteen boys with DCD( x=9.36 years +/- 0.68) and 13
      Controls ( x=9.16 years +/- 0.68) participated. Children performed 10 two-handed
      central catching trials, with the best five trials selected for analysis.
      RESULTS: The DCD group displayed greater variability in range of motion across
      all joint rotations in the catch phase. Specifically, increased shoulder flexion,
      thorax extension and elbow extension. Although the initiation of segmental
      movement occurred in the same order for the two groups, the DCD group initiated
      wrist extension considerably earlier. The DCD group also exhibited significant
      asymmetry in elbow flexion-extension. CONCLUSION: Despite success in performing
      this simple catching task (88% successful), the DCD group displayed an
      inefficient, variable and less symmetrical catching technique.

PMID- 22464637
TI  - Lower limb preference on goal-oriented tasks in unilateral prosthesis users.
AB  - The aim of this study was to determine lower limb preference in 31 prosthesis
      users and 19 able-bodied controls on 11 goal-oriented tasks in free-standing and
      supported conditions. The action leg used in 6 or more tasks was considered the
      preferred leg. We hypothesized that the prosthetic leg in amputees would be used
      as the preferred leg as often as the dominant leg in controls. For prosthesis
      users in the free-standing condition, 65% used the prosthetic leg as the
      preferred leg. This was significantly different (p<0.003) from able-bodied
      controls, where 100% used the dominant leg as the preferred leg. This discrepancy
      became even more pronounced in the supported condition and was overall more
      prevalent among those who used prosthesis for more than 10 years. These findings
      may have implications for therapy and gait training.

PMID- 22464638
TI  - Uncontrolled manifold analysis of gait variability: effects of load carriage and
      fatigue.
AB  - The uncontrolled manifold (UCM) analysis has been demonstrated to be a powerful
      tool for understanding motor variability. The purpose of this study was to use
      the UCM analysis to investigate the effects of load carriage and fatigue on gait
      variability. Whole-body kinematic data during treadmill walking were collected
      from 12 healthy male participants when fatigue and load carriage were applied.
      The task-level variable for the UCM analysis was selected to be the whole-body
      COM. We chose to analyze the whole-body COM data at two important gait events:
      right heel contact and right toe off, and the UCM analysis was carried out in the
      sagittal and frontal planes, separately. The dependent measures were UCM
      variability measures and UCM ratio. Three-way ANOVA was performed to determine
      the main and interaction effects of back-carrying load, fatigue, and gait events
      on the dependent measures. The results showed that frontal UCM ratio
      significantly changed with the application of back-carrying load and fatigue,
      indicating that both factors had effects on motor performance in stabilizing the
      whole-body COM in the frontal plane. These findings can facilitate a better
      understanding of the nature of motor variability due to load carriage and
      fatigue.

PMID- 22464639
TI  - Alpha-chymotrypcin ameliorates neuroinflammation and apoptosis characterizing
      Alzheimer's disease-induced in ovarictomized rats.
AB  - OBJECTIVE: Alzheimer's disease (AD) is the most common cause of dementia in the
      elderly. Very little is known about the causes of AD, except that its end stages
      involve extensive neuronal loss and the appearance of distinctive
      neuropathological features. This study was under taken to investigate the role of
      alpha-chymotrypcin (alpha-ch) in management of AD-induced in ovariectomized rats.
      DESIGN: Sixty female Sprague Dawley rats were divided into four groups n=15, (1)
      normal control group (con), (2) group underwent surgery to remove ovaries (ovx
      control group), (3) ovx group received aluminum chloride in a dose of 17 mg/kg
      daily for 2 months to induce AD (AD group), (4) AD group treated with alpha
      chymotrypcin (alpha-ch) at dose (8.1 unit/rat/day) which is equivalent to the
      recommended human dose (alpha-ch-treated group) for three months. At the end of
      the experimental period, rats were sacrificed; brain samples were obtained for
      different biochemical analyses and histopathological examination. The biochemical
      analyses included determination of tumor necrosis factor-alpha (TNF- alpha), IL
      18, monocyte chemo attractant protein-1 MCP-1, FAS, B-cell lymphoma 2 (Bcl2).
      RESULTS: In comparison with normal control group, the ovx control group recorded
      significant increase in the brain levels of TNF-alpha, IL-18, MCP-1 and FAS. On
      the other hand, the brain level of Bcl2 was significantly decreased. Also, AD
      group showed a significant increase in TNF-alpha, IL-18, MCP-1 and FAS levels in
      brain tissue. In contrast, significant decrease in brain Bcl2 level was detected
      in AD group as compared to the ovx control group. However, the treatment of AD
      group with alpha-chymotrypcin caused an improvement in the most studied
      biochemical parameters as indicated by decreased brain levels of TNF-alpha, IL
      18, MCP-1 and FAS accompanied with significant increase in the level of Bcl2
      compared to AD group. Histopathological investigation of brain tissue of ovx rats
      administered with aluminum (AD group) showed AD plaques. While, AD group treated
      with alpha-chymotrypcin showed great improvement in the brain morphological
      structure with the disappearance of amyloid plaques. CONCLUSION: This study
      revealed that alpha-chymotrypcin significantly ameliorates the neuroinflammation
      characterizing Alzheimer's disease in ovariectomized rats due to it's proteolytic
      activity as well as it's anti-inflammatory effect.

PMID- 22464640
TI  - Pain genetics: past, present and future.
AB  - Chronic pain is a classic example of gene * environment interaction: inflammatory
      and/or nerve injuries are known or suspected to be the etiology of most chronic
      pain syndromes, but only a small minority of those subjected to such injuries
      actually develop chronic pain. Once chronic pain has developed, pain severity and
      analgesic response are also highly variable among individuals. Although animal
      genetics studies have been ongoing for over two decades, only recently have
      comprehensive human twin studies and large-scale association studies been
      performed. Here, I review recent and accelerating progress in, and continuing
      challenges to, the identification of genes contributing to such variability.
      Success in this endeavor will hopefully lead to both better management of pain
      using currently available therapies and the development and/or prioritizing of
      new ones.

PMID- 22464641
TI  - Mycoplasma pneumoniae preceding Lemierre's syndrome due to Fusobacterium
      nucleatum complicated by acute Epstein-Barr virus (EBV) infectious mononucleosis
      in an immunocompetent host.
AB  - We report an unusual case of Lemierre's syndrome due to a rare species of
      Fusobacterium, that is, Fusobacterium nucleatum preceded by Mycoplasma pneumoniae
      pharyngitis and followed later by Epstein-Barr virus infectious mononucleosis.

PMID- 22464642
TI  - Update on risk factors for food allergy.
AB  - Despite efforts to prevent food allergy (FA) in children, IgE-mediated FAs are
      increasing in westernized countries. Previous preventive strategies, such as
      prolonged exclusive breast-feeding and delayed weaning onto solid foods, have
      recently been called into question. The present review considers possible risk
      factors and theories for the development of FA. An alternative hypothesis is
      proposed, suggesting that early cutaneous exposure to food protein through a
      disrupted skin barrier leads to allergic sensitization and that early oral
      exposure to food allergen induces tolerance. Novel interventional strategies to
      prevent the development of FA are also discussed.

PMID- 22464643
TI  - Food allergy diagnostic practice in Italian children.

PMID- 22464644
TI  - Intrauterine sensitization of allergen-specific IgE analyzed by a highly
      sensitive new allergen microarray.
AB  - BACKGROUND: To design a rational allergy prevention program, it is important to
      determine whether allergic sensitization starts in utero under the maternal
      immune system. OBJECTIVE: To investigate the origin of allergen-specific IgE
      antibodies in cord blood (CB) and maternofetal transfer of immunoglobulins.
      METHODS: The levels of food and inhalant allergen-specific IgE, IgA, IgG, and
      IgG(4) antibodies in CB and maternal blood (MB) from 92 paired neonates and
      mothers were measured by using a novel allergen microarray of diamond-like-carbon
      coated chip, with high-sensitivity detection of allergen-specific antibodies and
      allergen profiles. RESULTS: The levels of allergen-specific IgE antibodies
      against food and inhalant allergens and allergen profiles were identical in CB
      and newborn blood, but the levels and profiles, specifically against inhalant
      allergens, were different from those in MB. The level of allergen-specific IgA
      antibodies was below the detection levels in CB despite clear detection in MB.
      Therefore, contamination with MB in CB was excluded on the basis of extremely low
      levels of IgA antibodies in CB and the obvious mismatch of the allergen-specific
      IgE and IgA profiles between CB and MB. However, the levels of allergen-specific
      IgG and IgG(4) antibodies and their allergen profiles were almost identical in
      both MB and CB. CONCLUSION: Allergen-specific levels of IgE and IgA antibodies
      and their allergen profiles analyzed by the diamond-like-carbon allergen chip
      indicate that IgE antibodies in CB are of fetal origin. Food-allergen specific
      IgE antibodies were detected more often than inhalant-allergen specific IgE
      antibodies in CB, the reason of which remains unclarified.

PMID- 22464645
TI  - Combination inhaled corticosteroid and long-acting beta2-agonist use and severe
      asthma exacerbations.

PMID- 22464646
TI  - CD203c expression-based basophil activation test for diagnosis of wheat-dependent
      exercise-induced anaphylaxis.

PMID- 22464647
TI  - Intralymphatic immunotherapy for cat allergy induces tolerance after only 3
      injections.
AB  - BACKGROUND: Subcutaneous allergen-specific immunotherapy frequently causes
      allergic side effects and requires 30 to 80 injections over 3 to 5 years.
      OBJECTIVE: We sought to improve immunotherapy by using intralymphatic allergen
      administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to
      the MHC class II pathway. METHODS: Recombinant major cat dander allergen Fel d 1
      was fused to a translocation sequence (TAT) and to part of the human invariant
      chain, generating a modular antigen transporter (MAT) vaccine (MAT-Fel d 1). In a
      randomized double-blind trial ILIT with MAT-Fel d 1 in alum was compared with
      ILIT with placebo (saline in alum) in allergic patients
      (ClinicalTrials.govNCT00718679). RESULTS: ILIT with MAT-Fel d 1 elicited no
      adverse events. After 3 placebo injections within 2 months, nasal tolerance
      increased less than 3-fold, whereas 3 intralymphatic injections with MAT-Fel d 1
      increased nasal tolerance 74-fold (P < .001 vs placebo). ILIT with MAT-Fel d 1
      stimulated regulatory T-cell responses (P = .026 vs placebo) and increased cat
      dander-specific IgG(4) levels by 5.66-fold (P = .003). The IgG(4) response
      positively correlated with IL-10 production (P < .001). CONCLUSION: In a first-in
      human clinical study ILIT with MAT-Fel d 1 was safe and induced allergen
      tolerance after 3 injections.

PMID- 22464648
TI  - Esophageal eosinophilia caused by milk proteins: from suspicion to evidence based
      on 2 case reports.

PMID- 22464649
TI  - Diethylstilboestrol--a long-term legacy.
AB  - Diethylstilboestrol (DES) is an endocrine disrupter which causes cancer in
      rodents. It was prescribed in large amounts to treat women with gynaecological
      problems; some of the daughters of these women subsequently developed a rare
      cancer (vaginal clear cell adenocarcinoma) while genital abnormalities were found
      in some of the sons. It was used for decades in livestock feed and this may have
      contaminated the food chain leading to the exposure of the more general
      population. DES appears to cause epigenetic effects in animals and there is some
      evidence that this also occurs in man. The mechanisms of carcinogenesis are
      complex and the effects are difficult to prove due to the background of dietary
      and environmental phyto- and xenooestrogens. It has been suggested that, like
      other endocrine disrupters, DES may have acted as an obesogen in the human
      population.

PMID- 22464650
TI  - Protective antitumor immunity induced by tumor cell lysates conjugated with
      diphtheria toxin and adjuvant epitope in mouse breast tumor models.
AB  - Cancer cell vaccine-based immunotherapy has received increasing interest in many
      clinical trials involving patients with breast cancer. Combining with appropriate
      adjuvants can enhance the weak immunogenic properties of tumor cell lysates
      (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of
      mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were
      conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine
      was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively
      elicited tumor-specific polyclonal immune responses, including humoral and
      cellular immune responses. High levels of antibodies against TCL were detected in
      the serum of immunized mice with ELISA and verified with Western blot analyses.
      The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites
      carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2
      inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated
      tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor
      model. These findings demonstrate that TCL conjugated with appropriate adjuvants
      induced effective antitumor immunity in vivo. Improvements in potency could
      further make cancer cell vaccines a useful and safe method for preventing cancer
      recurrence after resection.

PMID- 22464651
TI  - Chondroblastoma in the long bone diaphysis: a report of two cases with literature
      review.
AB  - To investigate the clinical characteristics of chondroblastoma with an emphasis
      on lesions located in the long bone diaphysis, we reviewed the clinical data of 7
      patients with histologically proven chondroblastoma treated in Tianjin Medical
      University Cancer Hospital and Fudan University Cancer Hospital between January
      1995 and May 2009. There were two rare cases of chondroblastoma in the long bone
      diaphysis. One patient with a lesion in the tibial diaphysis underwent
      intralesional curettage and bone grafting, and the postoperative bone function
      was measured as excellent according to the Enneking scoring system. The patient
      was still alive upon follow-up at 60 months. The other patient with a lesion in
      the humeral diaphysis underwent resection, and the postoperative bone function
      was excellent at 48 months, at which there was no evidence of recurrence or
      metastasis. Thus, except for the distinctive site of the long bone diaphysis,
      which made diagnosis difficult, the patients' ages, symptoms, X-ray and CT
      images, treatment, and prognosis were in accordance with typical lesions in the
      epiphysis and metaphysis. The diagnosis of chondroblastoma in the long bone
      diaphysis significantly depends on histopathologic characteristics.

PMID- 22464653
TI  - Ischemic biliary injury following extra-corporeal membrane oxygenation (ECMO).

PMID- 22464652
TI  - MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in
      gastric cancer.
AB  - BACKGROUND: A thorough understanding of gastric cancer at the molecular level is
      urgently needed. One prominent oncogenic microRNA, miR-21, was previously
      reported to be upregulated in gastric cancer. METHODS: We performed an unbiased
      search for downstream messenger RNA targets of miR-21, based on miR-21
      dysregulation, by using human tissue specimens and the MKN28 human gastric
      carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA
      microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR
      21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by
      flow cytometry and luciferase reporter assay. RESULTS: This search identified
      Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct
      interaction between miR-21 and Serpini1 3'UTR. miR-21 and Serpini1 expression
      levels were inversely correlated in a subgroup of gastric cancers, suggesting a
      regulatory mechanism that included both of these molecules. Furthermore, Serpini1
      induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting
      its potential tumour-suppressive function in the stomach. CONCLUSION: Taken
      together, these data suggest that in a subgroup of gastric cancers, miR-21 is
      upregulated, inducing downregulation of Serpini1, which in turn releases the G1-S
      transition checkpoint, with the end result being increased tumour growth.

PMID- 22464654
TI  - Gossypiboma.

PMID- 22464655
TI  - Exploring the work of nurses who administer chemotherapy to children and young
      people.
AB  - PURPOSE OF THE RESEARCH: To explore the knowledge, attitudes and beliefs of
      nurses who administer chemotherapy to children and young people. METHODS AND
      SAMPLE: A national postal survey of nurses working within the 21 cancer centres
      in the United Kingdom and Ireland. The questionnaire included 25-items addressing
      the attitudes, beliefs and concerns regarding nurses' roles, support mechanisms
      and educational preparation related to administration of chemotherapy. RESULTS:
      In total 286/507 (56%) questionnaires were returned. The majority of nurses
      worked in inpatient +/-outpatient (78%) settings and most gave chemotherapy on a
      daily basis (61%). The median time working in oncology was 10 [range 0.5-32]
      years and time administering chemotherapy was 8 [0.1-32] years. Aspects of
      administration that caused the most worry included treatment side-effects,
      extravasation, dealing with allergic/anaphylactic reactions and knowledge
      deficits in colleagues. There was no significant difference in worry according to
      level of nurse education but those with an oncology qualification had less
      Knowledge-related worry (p = 0.05). There was no difference in attitude according
      to level of education or having an oncology qualification. There were significant
      correlations between time qualified, time working in oncology and the number of
      years administering chemotherapy and the worry domains (ranging from r = -0.14 to
      r = -0.24, p < 0.05); and attitude to chemotherapy (ranging from r = 0.12 to r =
      0.26, p < 0.001). CONCLUSION: As anticipated nurses new to chemotherapy
      administration were initially anxious about the role and they worried about
      making a drug error. Education and support from colleagues appears to have a
      positive effect on reducing worry and increasing competence.

PMID- 22464656
TI  - Recovery of posterior communicating artery aneurysm-induced oculomotor nerve
      paresis after endovascular treatment.
AB  - OBJECTIVE: Recovery of aneurysm-induced oculomotor nerve paresis (ONP) after
      endosaccular coiling has not yet been adequately assessed. The aim of this study
      was to investigate the factors that affect the outcome of ONP after endovascular
      treatment of posterior communicating artery (PcomA) aneurysms. MATERIALS AND
      METHODS: We retrospectively evaluated the clinical characteristics and the
      outcome of oculomotor nerve function in a series of 36 patients with ONP due to
      PcomA aneurysms treated by endovascular coiling. Univariate analysis was applied
      to test the association between ONP recovery and clinical variables. RESULTS:
      Thirty-six consecutive patients (20 women, 16 men; mean age, 54.3+/-9 years)
      presenting with ONP underwent endosaccular coiling were enrolled in this study.
      Subarachnoid hemorrhage was present in 21 patients. The mean size of the
      aneurysms was 9.3+/-3.9mm. ONP was complete in 14 patients (38.9%) and partial in
      22 patients (61.1%) at admission. Seventeen patients (47.2%) had complete
      recovery of oculomotor nerve function, 15 had incomplete recovery (41.7%), and 4
      (11.1%) remained unchanged after treatment. Factors showing significant
      association with recovery of oculomotor nerve function were the length and degree
      of ONP before treatment (P=0.035 and P=0.019, respectively). CONCLUSIONS:
      Endosaccular coiling of PcomA aneurysms in patients with ONP resulted in cure or
      improvement of oculomotor nerve dysfunction in the majority of patients. The
      length and degree of preoperative ONP were the statistically significant
      predictors of complete ONP recovery.

PMID- 22464658
TI  - Development of dural plasmacytoma after evacuation of chronic subdural hematoma:
      case report.

PMID- 22464657
TI  - Neuromodulation of lower limb motor control in restorative neurology.
AB  - One consequence of central nervous system injury or disease is the impairment of
      neural control of movement, resulting in spasticity and paralysis. To enhance
      recovery, restorative neurology procedures modify altered, yet preserved nervous
      system function. This review focuses on functional electrical stimulation (FES)
      and spinal cord stimulation (SCS) that utilize remaining capabilities of the
      distal apparatus of spinal cord, peripheral nerves and muscles in upper motor
      neuron dysfunctions. FES for the immediate generation of lower limb movement
      along with current rehabilitative techniques is reviewed. The potential of SCS
      for controlling spinal spasticity and enhancing lower limb function in multiple
      sclerosis and spinal cord injury is discussed. The necessity for precise
      electrode placement and appropriate stimulation parameter settings to achieve
      therapeutic specificity is elaborated. This will lead to our human work of
      epidural and transcutaneous stimulation targeting the lumbar spinal cord for
      enhancing motor functions in spinal cord injured people, supplemented by
      pertinent human research of other investigators. We conclude that the concept of
      restorative neurology recently received new appreciation by accumulated evidence
      for locomotor circuits residing in the human spinal cord. Technological and
      clinical advancements need to follow for a major impact on the functional
      recovery in individuals with severe damage to their motor system.

PMID- 22464659
TI  - Outcomes and perception of lung surgery with implementation of a patient video
      education module: a prospective cohort study.
AB  - BACKGROUND: Although surgeons are constantly making efforts to improve efficiency
      of care, it is important to also optimize the patients' understanding and
      satisfaction with their surgical experience. We investigated the effect of a
      preoperative educational video on patient outcomes and perception of surgery.
      STUDY DESIGN: An educational video was developed outlining preoperative,
      operative, and postoperative expectations for patients undergoing pulmonary
      resection. A prospective study was conducted with 150 patients undergoing surgery
      with routine preoperative discussion (control group, January 2008 to June 2009)
      and 150 patients who were provided a supplemental video module (video or study
      group, September 2009 to October 2010) in addition to routine discussion.
      Demographics and outcomes data were recorded. Patients completed a pain survey
      (McGill Questionnaire) and a standardized patient satisfaction survey at
      discharge and within 1 month of operation. RESULTS: The groups were similar in
      sex, age, comorbidities, and forced expiratory volume, 1 second, % predicted.
      Length of hospital stay (5.19 +/- 7.4 days vs 4.31 +/- 4.3 days; p = 0.2) and
      hospital readmission rates (12 of 134 [9%] vs 5 of 103 [4.9%]; p = 0.3) were
      similar for the 2 groups. At discharge, patients in the study group reported less
      pain at rest (0.98 +/- 0.09) vs controls (1.39 +/- 0.11) (p = 0.01) with no
      difference in pain with lifting or coughing. Patients in the study group reported
      better overall satisfaction with their operation (2.14 +/- 0.07 vs 1.85 +/- 0.07;
      p = 0.02), believed they were better prepared (2.01 +/- 0.07 vs 1.70 +/- 0.06; p
      = 0.006), and reported less anxiety about the surgical experience (2.79 +/- 0.10
      vs 2.24 +/- 0.09; p = 0.0001). CONCLUSIONS: Implementation of a pulmonary
      resection education module improves patient preparedness, relieves anxiety, and
      improves pain perception. Additional development and dissemination of a
      comprehensive education program can improve patients' experience with lung
      surgery and impact outcomes.

PMID- 22464660
TI  - Certification by the American Board of Surgery among US medical school graduates.
AB  - BACKGROUND: We sought to identify variables associated with American Board of
      Medical Specialties (ABMS)-member board certification and lack thereof among US
      medical graduates who planned at medical school graduation to become certified in
      surgery and entered graduate medical education in general surgery. STUDY DESIGN:
      Deidentified, individualized records updated through March 2009 for all 1993-2000
      US medical school matriculants who graduated by 2002, intended to become
      certified in surgery, and entered general surgery training were analyzed using
      multivariable logistic regression to identify variables associated with
      graduates' board certification status, including American Board of Surgery (ABS)
      board certified (BC), other ABMS-member-BC (other-BC) and non-BC. RESULTS: Of
      3,373 graduates included in the study sample, 2,036 (60.4 %) were ABS-BC, 342
      (10.1 %) were other-BC, and 995 (29.5 %) were non-BC. Graduates who were women,
      older than 26 years old at graduation, and initially failed US Medical Licensing
      Examination Step 2 Clinical Knowledge were more likely, and graduates who rated
      the quality of their surgery clerkship in medical school more highly were less
      likely, to be other-BC vs ABS-BC. Graduates who were women, under-represented
      minority race/ethnicity, Asian/Pacific Islander race/ethnicity, older than 28
      years old at graduation, initially failed US Medical Licensing Examination Step
      l, initially failed or received low passing scores on US Medical Licensing
      Examination Step 2 Clinical Knowledge, and graduated in more recent years were
      more likely to be non-BC vs ABS-BC. CONCLUSIONS: Demographic and professional
      development variables were associated with ABMS-member BC status among US medical
      graduates who had intended at medical school graduation to become certified in
      surgery.

PMID- 22464661
TI  - Predictive factors of early bowel obstruction in colon and rectal surgery: data
      from the Nationwide Inpatient Sample, 2006-2008.
AB  - BACKGROUND: Early postoperative bowel obstruction is associated with considerable
      morbidity and mortality after colorectal surgery. We evaluated the impact of
      patient characteristics, patient comorbidities, pathology, resection site,
      surgical technique, admission type, and teaching hospital status on the incidence
      of in-hospital bowel obstruction after colorectal surgery. STUDY DESIGN: Using
      the Nationwide Inpatient Sample database, we examined the clinical data of
      patients who underwent colorectal resection from 2006 to 2008. Regression
      analyses were performed to identify factors predictive of in-hospital bowel
      obstruction. RESULTS: A total of 975,825 patients underwent colorectal resection
      during this period. Overall, the rate of postoperative bowel obstruction was
      8.65% (elective surgery: 5.32% vs emergent surgery: 13.26%; p < 0.01). Bowel
      obstruction was less frequent after laparoscopic procedures compared with open
      procedures (6.61% vs 8.81%; p < 0.01). Using multivariate regression analysis,
      Crohn disease (adjusted odds ratio [AOR] = 12.32), emergent surgery (AOR = 2.54),
      malignant tumor (AOR = 1.84), diverticulitis (AOR = 1.45), age older than 65
      years (AOR = 1.22), female sex (AOR = 1.14), history of alcohol abuse (AOR =
      1.12), transverse colectomy (AOR = 1.11), peripheral vascular disease (AOR =
      1.07), left colectomy (AOR = 1.06), chronic lung disease (AOR = 1.05), open
      procedure (AOR = 1.05), African-American race (AOR = 1.03), and teaching hospital
      (AOR = 1.02) were associated with a higher risk of in-hospital bowel obstruction.
      There was no association between hypertension, diabetes, congestive heart
      failure, chronic renal failure, liver disease, obesity, smoking, proctectomy or
      total colectomy, and early bowel obstruction. CONCLUSIONS: Early bowel
      obstruction is a relatively common complication after colorectal surgery. Crohn
      disease patients had a 12-fold higher incidence of early bowel obstruction, and
      emergent surgery and malignancy were relevant predictors of early bowel
      obstruction.

PMID- 22464662
TI  - Echo around the world.

PMID- 22464664
TI  - The ASE is a society of advocates!

PMID- 22464665
TI  - Communicating shared decision-making: cancer patient perspectives.
AB  - OBJECTIVE: To contribute to the evolving dialogue on optimizing cancer care
      communication through systematic analyzes of patients' perspectives. METHODS:
      Using constant comparative analysis, inductively derived thematic patterns of
      communication preferences for shared decision-making were drawn from individual
      interviews with 60 cancer patients. RESULTS: Thematic patterns in how patients
      understand barriers and facilitators to communication within shared decision
      making illuminate the basis for distinctive patient preferences and needs.
      Prevailing cancer communication considerations included focusing attention on the
      tone and setting of the consultation environment, the attitudinal climate within
      the consult, the specific approach to handling numerical/statistical information,
      and the critical messaging around hope. The patient accounts surfaced complex
      dynamics whereby the experiences of living with cancer permeated interpretations
      and enactment of the shared decision-making that is emerging as a dominant ideal
      of cancer care. CONCLUSION: In our efforts to move beyond traditional
      paternalism, shared decision-making has been widely advocated as best practice in
      cancer communication. However, patient experiential evidence suggests the
      necessity of a careful balance between standardized approaches and respect for
      diversities. PRACTICE IMPLICATIONS: Shared decision-making as a practice standard
      must be balanced against individual patient preferences.

PMID- 22464666
TI  - Do the public share practitioners' views about the best evidence?
AB  - OBJECTIVE: To investigate whether general practitioners (GPs) and patients agree
      on what constitutes the best evidence for the effectiveness of treatments.
      METHODS: GPs and members of the public aged 18-83 read five scenarios describing
      comparisons between hypothetical treatments for common ailments. Each scenario
      reported that one treatment was the more effective, as determined by randomised
      controlled trial (RCT), audit of treatment outcomes from many doctors' patients,
      a single doctor's clinical experience, a friend's experience, or a web-based
      sales site. Participants rated how confident they would be that the treatment
      reported to be more effective would work for them. RESULTS: All participants had
      least confidence in the web-based sales site, more confidence in a friend's
      experience and more still in one doctor's experience. For doctor's experience,
      audit and RCT, amongst the public there were some differences by age but,
      importantly, only GPs had most confidence in evidence from an RCT. CONCLUSION:
      GPs may treat evidence from RCTs as the gold standard while members of the public
      (their patients) may not afford it that same respect. PRACTICE IMPLICATIONS: GPs
      engaged in shared decision-making should be alert to possible differences from
      their patients in the weight given to different types of evidence.

PMID- 22464667
TI  - Blood lead level modifies the association between dietary antioxidants and
      oxidative stress in an urban adult population.
AB  - Oxidative stress may be affected by lead exposure as well as antioxidants, yet
      little is known about the interaction between dietary antioxidants and blood lead
      levels (BLL) on oxidative stress level. We investigated the interaction between
      dietary antioxidants and BLL on oxidative stress level. As part of the Biomarker
      Monitoring for Environmental Health conducted in Seoul and Incheon, Korea,
      between April and December 2005, we analysed data from 683 adults (female = 47.4
      %, mean age 51.4 (sd 8.4) years) who had complete measures on BLL, dietary
      intakes and oxidative stress marker (urinary 8-hydroxy-2'-deoxyguanosine (8
      OHdG)). Dietary intakes were assessed by a validated semi-quantitative FFQ, BLL
      was measured using atomic absorption spectrophotometry, and 8-OHdG by ELISA.
      Multivariate linear regression analyses were used to evaluate the influence of
      BLL on the association between dietary antioxidants and 8-OHdG. Geometric means
      of BLL and 8-OHdG concentrations were 4.1 (sd 1.5) MUg/dl and 5.4 (sd 1.9) MUg/g
      creatinine, respectively. Increases of vitamins C and E were significantly
      associated with the decrease of log10 8-OHdG in the adults from the lowest
      quartile of the BLL group (<= 3.18 MUg/dl, geometric mean = 2.36 MUg/dl) than
      those of the highest quartile BLL group (>5.36 MUg/dl, geometric mean = 6.78
      MUg/dl). Regarding antioxidant-related foods, vegetables excluding kimchi showed
      a higher inverse relationship with 8-OHdG in the lowest quartile BLL group than
      the highest group. These findings suggest a rationale for lowering the BLL and
      increasing the intake of dietary antioxidants in the urban population in Korea.

PMID- 22464668
TI  - The role of dendritic cells in asthma.
AB  - Dendritic cells (DCs) are known to play a central role in sensing the presence of
      foreign antigens and infectious agents and in initiating appropriate immune
      responses. More recently, an additional role has been discovered for DCs in
      determining whether the response to potential environmental allergens will be one
      of tolerance or whether a vigorous response along allergic pathways will be
      initiated. This review discusses ways in which DCs participate specifically in
      initiating allergic responses, particularly those associated with allergic
      asthma, and how interventions focused on DCs might lead to new therapeutic
      approaches to asthma.

PMID- 22464669
TI  - The role of dendritic cells in food allergy.
AB  - In recent years, our understanding of the initiation of T(H)2-type immunity has
      increased significantly, yet the mechanism behind the induction of T(H)2
      responses and allergic sensitization to food antigens largely remains an enigma.
      Dendritic cells (DCs) were first described almost 4 decades ago and have since
      been recognized as the most important antigen-presenting cells and crucial in the
      induction of T-cell differentiation. Here we discuss our current knowledge of the
      role of DCs in food allergy. In both murine models and allergic patients,
      characteristics of DCs have been identified that might play a role in
      sensitization to food and enhance susceptibility to food allergy. In addition, it
      has now been shown that several allergens, including some from foods, can
      directly activate DCs to induce T(H)2 skewing. Other cell types with innate
      immune functions, such as epithelial cells and basophils, might also be involved
      in sensing of food allergens in human subjects, and interaction of DCs with these
      cells might facilitate sensitization. DCs appear to play an important role in
      allergen-specific immunotherapy and could be an attractive target for tolerance
      induction in patients with food allergy. Further characterization of differences
      in DC responses between human food-allergic and nonallergic subjects is necessary
      to gain a better insight into the role of DCs in sensitization and tolerance to
      food allergens.

PMID- 22464671
TI  - The airway epithelium in childhood asthma.

PMID- 22464672
TI  - T(H)9 cells: in front and beyond T(H)2.

PMID- 22464673
TI  - A regulatory dendritic cell signature correlates with the clinical efficacy of
      allergen-specific sublingual immunotherapy.
AB  - BACKGROUND: Given their pivotal role in the polarization of T-cell responses,
      molecular changes at the level of dendritic cells (DCs) could represent an early
      signature indicative of the subsequent orientation of adaptive immune responses
      during immunotherapy. OBJECTIVE: We sought to investigate whether markers of
      effector and regulatory DCs are affected during allergen immunotherapy in
      relationship with clinical benefit. METHODS: Differential gel electrophoresis and
      label-free mass spectrometry approaches were used to compare whole proteomes from
      human monocyte-derived DCs differentiated toward either regulatory or effector
      functions. The expression of those markers was assessed by using quantitative PCR
      in PBMCs from 79 patients with grass pollen allergy enrolled in a double-blind,
      placebo-controlled clinical study evaluating the efficacy of sublingual tablets
      in an allergen exposure chamber over a 4-month period. RESULTS: We identified
      several markers associated with DC1 and/or DC17 effector DCs, including CD71,
      FSCN1, IRF4, NMES1, MX1, TRAF1. A substantial phenotypic heterogeneity was
      observed among various types of tolerogenic DCs, with ANXA1, Complement component
      1 (C1Q), CATC, GILZ, F13A, FKBP5, Stabilin-1 (STAB1), and TPP1 molecules
      established as shared or restricted regulatory DC markers. The expression of 2 of
      those DCs markers, C1Q and STAB1, was increased in PBMCs from clinical responders
      in contrast to that seen in nonresponders or placebo-treated patients.
      CONCLUSION: C1Q and STAB1 represent candidate biomarkers of early efficacy of
      allergen immunotherapy as the hallmark of a regulatory innate immune response
      predictive of clinical tolerance.

PMID- 22464674
TI  - Oral application of bacterial lysate in infancy decreases the risk of atopic
      dermatitis in children with 1 atopic parent in a randomized, placebo-controlled
      trial.
AB  - BACKGROUND: Lower prevalence of atopy was found in children with continuous
      exposure to livestock and thus to microbial compounds. In animal models exposure
      to endotoxin (LPS) decreases allergic sensitization and airway inflammation.
      OBJECTIVE: We sought to evaluate the effect of orally applied bacterial lysate in
      infancy on the prevalence of atopic dermatitis (AD) after the treatment phase at
      7 months of age. METHODS: This randomized, placebo-controlled trial included 606
      newborns with at least single heredity for atopy. From week 5 until the end of
      month 7, infants were treated orally with bacterial lysate containing heat-killed
      gram-negative Escherichia coli Symbio and gram-positive Enterococcus faecalis
      Symbio or its placebo. Children were followed until 3 years of age. RESULTS:
      There was no difference in the primary outcome between the active and placebo
      groups in the total study group. AD prevalence was significantly reduced at the
      end of the intervention phase (31 weeks of age) in the subgroup of infants with
      single heredity for atopy (relative risk, 0.52; 95% CI, 0.3-0.9). Ten percent
      (15/154) of infants in the active group had AD compared with 19% (27/145, P =
      .030) in the placebo group. This was more pronounced in the group of infants with
      paternal heredity for atopy (11% vs 32%, P = .004; relative risk, 0.34; 95% CI,
      0.2-0.7). CONCLUSION: Feeding of bacterial lysate might have prevented the
      development of AD, especially in children with paternal atopy, possibly
      indicating a preventive property only in subjects with a limited risk for atopy.

PMID- 22464675
TI  - Morphologic and immunohistochemical characterization of granulomas in the
      nucleotide oligomerization domain 2-related disorders Blau syndrome and Crohn
      disease.
AB  - BACKGROUND: Blau syndrome (BS) and Crohn disease (CD) are both characterized by
      granulomatous inflammation and related to nucleotide oligomerization domain 2
      (NOD2) mutations. OBJECTIVE: This study aimed to define the morphologic and
      immunohistochemical characteristics of granulomas in patients with NOD2-related
      BS and CD. METHODS: Granuloma-containing biopsy specimens from 6 patients with BS
      and 7 pediatric patients with CD carrying NOD2 mutations or single nucleotide
      polymorphisms were studied for morphology, cellular composition, and cytokine
      expression by using hematoxylin and eosin staining and immunohistochemistry.
      RESULTS: Biopsy specimens from patients with BS typically showed polycyclic
      granulomas with large lymphocytic coronas, extensive emperipolesis of lymphocytes
      within multinucleated giant cells (MGCs), MGC death, and fibrinoid necrosis and
      fibrosis. In contrast, biopsy specimens from patients with CD showed simple
      granulomas with subtle/absent lymphocytic coronas, sclerosis of the surrounding
      tissue, and polymorphonuclear cells. Findings found to be similar in all
      granulomas were as follows: CD68 and HLA-DR expression by epithelioid cells,
      monocyte-macrophage lineage cells and MGCs, increased lymphocytic HLA-DR
      expression, increased CD4(+)/CD8(+) T-cell ratio, and CD20(+) B lymphocytes
      evenly distributed within and around granulomas. In both patient groups prominent
      IFN-gamma expression was found in and around granulomas, and TNF-alpha and IL-23
      receptor expression was moderate. IL-6, IL-17, and TGF-beta expression was
      prominent in granulomas from patients with BS but sporadic in granulomas from
      patients with CD. IL-10 expression was absent. CONCLUSION: Granulomas from
      patients with BS and granulomas from patients with NOD2-associated CD show
      distinct morphologic features and cytokine expression patterns, suggesting that
      the T(H)17 axis might be involved in the pathogenesis of BS, whereas T(H)1 is
      important in both patients with BS and patients with CD.

PMID- 22464676
TI  - Nonimmediate drug allergy: diagnostic benefit of skin testing and practical
      approach.

PMID- 22464677
TI  - Elf5, hormones and cell fate.
AB  - Recent elucidation of the stem and progenitor cell hierarchies that operate
      during normal tissue and organ development has provided a foundation for the
      development of new insights into the disease process. These hierarchies are
      established by genetic mechanisms, which specify and determine cell fate and act
      as cell-clade gatekeepers, upon which all multicellular organisms depend for
      viability. Perturbation of this gatekeeper function characterizes developmentally
      based diseases, such as cancer. Here, the emerging gatekeeper and master
      regulatory roles of the ETS transcription factor Elf5 in several diverse
      developmental scenarios is reviewed, and how this function intersects with
      hormonal and growth factor mediated regulation of these processes is shown.

PMID- 22464678
TI  - A flexible diet using an insulin to carbohydrate ratio for adolescents with type
      1 diabetes - a pilot study.
AB  - BACKGROUND & AIMS: There is significant interest in the utility of flexible meal
      plans for individuals with type 1 diabetes. However, there is a paucity of data
      examining this approach in adolescents. The aim of this study was to assess
      glycemic control, weight status and quality of life over 12 months in adolescents
      with type 1 diabetes, who were commenced on a flexible meal plan using an insulin
      to carbohydrate ratio. METHODS: 38 adolescents with type 1 diabetes were
      recruited and 28 completed the study. Glyceamic control, weight status and
      quality of life were measured using haemoglobin A1c, BMI and the Diabetes Quality
      of Life -Youth questionnaire. RESULTS: Nine months after the adolescents were
      transitioned to a flexible meal and insulin plan, mean BMI SDS decreased (by 0.15
      +/- 0.20; P < 0.001) and haemoglobin A1c increased (by 0.7 +/- 0.83%; P = 0.001).
      Adolescents reported no change in the impact or concerns about diabetes. However,
      mean life satisfaction scores increased (5.5 +/- 9.5; P = 0.008). CONCLUSIONS: On
      a flexible meal and insulin plan glycemic control deteriorated although weight
      status and life satisfaction, two outcomes which may be important to the
      adolescents, improved. A flexible meal and insulin plan warrants further
      investigation as a management option.

PMID- 22464679
TI  - Comparison of heart rate variability among children with well controlled versus
      refractory epilepsy: a cross-sectional study.
AB  - PURPOSE: Autonomic symptoms frequently occur during seizures. There are reports
      that the adult group of intractable epilepsy patients have different autonomic
      profile than the well controlled epilepsy, but there is no clear evidence in the
      children epilepsy group, therefore, we planned to study the autonomic profile in
      well controlled and refractory epilepsy children by recording the short-term
      heart rate variability (HRV). METHODS: This cross sectional study was conducted
      in a tertiary care hospital between July 2008 and June 2009. Children with mean
      age of 9.1+/-3.3 years were enrolled. Three groups of children, 40 in each group
      namely, refractory epilepsy, well controlled epilepsy and normal control children
      were included. Children who had chronic systemic diseases and were on drugs that
      cause autonomic dysfunction were excluded. All children underwent short term
      heart rate variability testing. Data was analyzed in time domain and frequency
      domain. RESULTS: pNN50 was significantly lower in children with refractory
      epilepsy than the well control as well as healthy controls. Rest of the
      parameters of time domain and frequency domain were comparable between the
      groups. CONCLUSIONS: Our study showed that parasympathetic activity is lower in
      refractory epilepsy children. However, autonomic tone is comparable in well
      control versus healthy controls.

PMID- 22464680
TI  - Probing the general time scale question of boronic acid binding with sugars in
      aqueous solution at physiological pH.
AB  - The boronic acid group is widely used in chemosensor design due to its ability to
      reversibly bind diol-containing compounds. The thermodynamic properties of the
      boronic acid-diol binding process have been investigated extensively. However,
      there are few studies of the kinetic properties of such binding processes. In
      this report, stopped-flow method was used for the first time to study the kinetic
      properties of the binding between three model arylboronic acids, 4-, 5-, and 8
      isoquinolinylboronic acids, and various sugars. With all the boronic acid-diol
      pairs examined, reactions were complete within seconds. The k(on) values with
      various sugars follow the order of D-fructose>D-tagatose>D-mannose>D-glucose.
      This trend tracks the thermodynamic binding affinities for these sugars and
      demonstrates that the 'on' rate is the key factor determining the binding
      constant.

PMID- 22464681
TI  - Ester and carbamate ester derivatives of Biochanin A: synthesis and in vitro
      evaluation of estrogenic and antiproliferative activities.
AB  - Biochanin A (BCA), a major isoflavone in red clover and many other legumes, has
      been reported to display estrogenic as well as cancer chemopreventive properties.
      Ingested BCA is known to display low bioavailability due to poor solubility,
      extensive metabolism and rapid clearance. Esters of bioactive isoflavones are
      known to increase metabolic stability and bioavailability following local rather
      than systemic administration. We synthesized BCA from phloroglucinol and p
      methoxy-phenylacetic acid by a Friedel-Crafts reaction and cyclization. We also
      synthesized esters (1, 3) and carbamate esters (2, 4, 5) at position 7 of BCA
      using short aliphatic chains bearing a chlorine (1, 2) or a bromine atom (3, 4)
      or long aliphatic chains without such atoms (5). We tested the estrogenic and
      antiproliferative activities of 1-5 and BCA using human breast and endometrial
      adenocarcinoma cells. We found that 5 affects MCF-7 and Ishikawa cells in a
      manner providing for induction of gene expression to a level similar to 17beta
      estradiol and BCA but, unlike both of the latter, for suppression of cell
      proliferation as well. In addition, 5 appeared to display higher stability
      compared to 1-4 and BCA in both MCF-7 and Ishikawa cells. The inference is that 5
      may represent a safer than BCA alternative to hormone replacement therapy.

PMID- 22464682
TI  - Who cares for the protons?
AB  - It is tempting to use standard protonation states for the analysis of protein
      ligand interactions. Two different pK(a) calculation methods, PROPKA (protein
      pK(a)) and MCCE (multi conformation continuum electrostatics), were applied to
      challenge this convenient behavior. As data basis, we selected five recently
      approved drugs for which structural information of the protein-drug complex is
      available. We analyzed the pK(a) calculations in terms of a measure termed BIPS
      (binary protonation states) recently introduced by us. Both methods agree in
      detecting the majority of the sites with atypical BIPS values. However, when
      using only one method, some of the atypcial BIPS value would have been missed.
      Therefore, we recommend using both methods to set such an interpretation on a
      solid basis.

PMID- 22464683
TI  - Molecular docking and enzymatic evaluation to identify selective inhibitors of
      aspartate semialdehyde dehydrogenase.
AB  - Microbes that have gained resistance against antibiotics pose a major emerging
      threat to human health. New targets must be identified that will guide the
      development of new classes of antibiotics. The selective inhibition of key
      microbial enzymes that are responsible for the biosynthesis of essential
      metabolites can be an effective way to counter this growing threat. Aspartate
      semialdehyde dehydrogenases (ASADHs) produce an early branch point metabolite in
      a microbial biosynthetic pathway for essential amino acids and for quorum sensing
      molecules. In this study, molecular modeling and docking studies were performed
      to achieve two key objectives that are important for the identification of new
      selective inhibitors of ASADH. First, virtual screening of a small library of
      compounds was used to identify new core structures that could serve as potential
      inhibitors of the ASADHs. Compounds have been identified from diverse chemical
      classes that are predicted to bind to ASADH with high affinity. Next, molecular
      docking studies were used to prioritize analogs within each class for synthesis
      and testing against representative bacterial forms of ASADH from Streptococcus
      pneumoniae and Vibrio cholerae. These studies have led to new micromolar
      inhibitors of ASADH, demonstrating the utility of this molecular modeling and
      docking approach for the identification of new classes of potential enzyme
      inhibitors.

PMID- 22464685
TI  - Antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid
      pharmacophores.
AB  - A series of novel keto-enamine chalcone-chloroquine based hybrids were
      synthesized following new methodology developed in our laboratory. The
      synthesized compounds were screened against chloroquine sensitive strain (3D7) of
      Plasmodium falciparum in an in vitro model. Some of the compounds were showing
      comparable antimalarial activity at par with chloroquine. Compounds with
      significant in vitro antimalarial activity were then evaluated for their in vivo
      efficacy in Swiss mice against Plasmodium yoelii (chloroquine resistant N-67
      strain), wherein compounds 25 and 27 each showed an in vivo suppression of 99.9%
      parasitaemia on day 4. Biochemical studies reveal that inhibition of hemozoin
      formation is the primary mechanism of action of these analogues.

PMID- 22464684
TI  - Semisynthetic neoclerodanes as kappa opioid receptor probes.
AB  - Modification of the furan ring of salvinorin A (1), the main active component of
      Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid
      receptor affinity and activity. Conversion of the furan ring to an aldehyde at
      the C-12 position (5) has allowed for the synthesis of analogues with new carbon
      carbon bonds at that position. Previous methods for forming these bonds, such as
      Grignard and Stille conditions, have met with limited success. We report a
      palladium catalyzed Liebeskind-Srogl cross-coupling reaction of a thioester and a
      boronic acid that occurs at neutral pH and ambient temperature to produce ketone
      analogs at C-12. To the best of our knowledge, this is the first reported usage
      of the Liebeskind-Srogl reaction to diversify a natural product scaffold. We also
      describe a one-step protocol for the conversion of 1 to 12-epi-1 (3) through
      microwave irradiation. Previously, this synthetically challenging process has
      required multiple steps. Additionally, we report in this study that alkene 9 and
      aromatic analogues 12, 19, 23, 25, and 26 were discovered to retain affinity and
      selectivity at kappa opioid receptors (KOP). Finally, we report that the furan-2
      yl analog of 1 (31) has similar affinity to 1. Collectively, these findings
      suggest that different aromatic groups appended directly to the decalin core may
      be well tolerated by KOP receptors, and may generate further ligands with
      affinity and activity at KOP receptors.

PMID- 22464686
TI  - Synthesis and biological evaluation of a series of thieno-expanded tricyclic
      purine 2'-deoxy nucleoside analogues.
AB  - Introducing structural diversity into the nucleoside scaffold for use as
      potential chemotherapeutics has long been considered an important approach to
      drug design. In that regard, we have designed and synthesized a number of
      innovative 2'-deoxy expanded nucleosides where a heteroaromatic thiophene spacer
      ring has been inserted in between the imidazole and pyrimidine ring systems of
      the natural purine scaffold. The synthetic efforts towards realizing the expanded
      2'-deoxy-guanosine and -adenosine tricyclic analogues as well as the preliminary
      biological results are presented herein.

PMID- 22464687
TI  - Discovery of novel tricyclic compounds as squalene synthase inhibitors.
AB  - In the present article, we have reported the design, synthesis, and
      identification of highly potent benzhydrol derivatives as squalene synthase
      inhibitors (compound 1). Unfortunately, the in vivo efficacies of the compounds
      were not enough for acquiring the clinical candidate. We continued our
      investigation to obtain a more in vivo efficacious template than the benzhydrol
      template. In our effort, we focused on a benzoxazepine ring and designed a new
      tricyclic scaffold by the incorporation of heterocycle into it. Prepared
      pyrrolobenzoxazepine derivatives showed further efficient in vitro and in vivo
      activities.

PMID- 22464688
TI  - Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive
      structure-activity study.
AB  - Pilicides prevent pili formation and thereby the development of bacterial
      biofilms in Escherichia coli. We have performed a comprehensive structure
      activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone
      pilicide central fragment by varying all open positions. Orthogonal projections
      to latent structures discriminant analysis (OPLS-DA) was used to distinguish
      active from inactive compounds in which polarity proved to be the most important
      factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS)
      model was calculated on the active compounds for prediction of biofilm inhibition
      activity. In this model, compounds with high inhibitory activity were generally
      larger, more lipophilic, more flexible and had a lower HOMO. Overall, this
      resulted in both highly valuable SAR information and potent inhibitors of type 1
      pili dependent biofilm formation. The most potent biofilm inhibitor had an EC(50)
      of 400 nM.

PMID- 22464689
TI  - Anethole suppressed cell survival and induced apoptosis in human breast cancer
      cells independent of estrogen receptor status.
AB  - BACKGROUND: Many traditional Chinese medicines target the treatment of
      inflammation which is emerging to be a critical component to cancer development
      and progression. The key aromatic compound in star anise anethole has
      demonstrated both anti and pro-cancerous effects depending on the estrogen
      receptor statuses in individual cell lines. In this study, we investigated the
      effect of anethole on the physiological responses and specific apoptotic pathways
      in human breast cancer MCF-7 and MDA-MB-231 cells that are well-characterized to
      represent estrogen receptor (ER) positivity and its counterpart in breast cancer
      respectively. How anethole affects the activity and expression of apoptotic
      caspases, the function of transcriptional factor NF-kB and the relative influence
      ER exerts on these events are areas of significant research relevance and results
      may impact the pharmaceutical development of anethole and its use as dietary
      supplementation. METHODOLOGY/PRINCIPAL FINDINGS: Initial analyses of
      physiological responses using MTT and colony formation assays had demonstrated a
      preferentially suppression of cell survival to cell proliferation in both ER+ and
      ER- cells when cells were exposed to anethole. Western blot analysis has
      demonstrated induction of caspase 9 and PARP1/2 cleavage in parallel with
      elevated expression of c-FLIP (s) and p53. The transcriptional activity of NF-kB,
      an upstream activator of p53 is suppressed in both cell lines when treated with
      anethole. CONCLUSIONS: In conclusion, anethole in an ER independent manner
      suppresses cell survival and induces apoptotic events in MCF-7 and MDA-MB-231 at
      an optimal concentration of 1 * 10(-3)M. In search of alternative compounds for
      therapeutic development, this study has demonstrated that anethole may be viable
      as an anti-cancer agent through the modulation of apoptosis, cell survival and
      proliferation in breast cancer cells.

PMID- 22464691
TI  - Effect of exenatide, pen insulin, and vial insulin on patient outcomes: a
      retrospective database analysis of persistence and first-year costs in a
      commercially insured population.
AB  - OBJECTIVE: We compared health care costs and medication persistence for patients
      with type 2 diabetes initiating treatment using exenatide, pen insulin, or vial
      insulin. METHODS: Commercial health plan data (2004-2008) were used to identify
      episodes of antidiabetic drug therapy, which were then classified according to
      treatment history: first observed treatment, restarting a previous therapy (90
      day gap in all treatment), switching therapy, and augmentation therapy. Three
      time periods were defined for each episode: the month in which the episode was
      initiated (index month), 6 months before the index month (preindex period), and
      12 months after the index month (postindex period). All exenatide and insulin
      episodes were selected for this analysis of persistence and first-year costs.
      Multivariate statistical methods were adjusted for demographic characteristics,
      drug use history, previous medical care use, comorbid medical conditions, and
      prescription drug profile. Several sensitivity analyses were conducted. RESULTS:
      A total of 213,701 episodes of antidiabetic drug therapy were identified, of
      which 7031 patients were initiated using exenatide, 21,011 used vial insulin, and
      422 used pen insulin. Time to all-cause discontinuation (TTAD) was measured for
      the index drug and all diabetic-related drugs. Pen insulin was discontinued 91
      days earlier than exenatide, whereas vial insulin was continued 18 days longer
      than exenatide. Patients using pen insulin discontinued all antidiabetic drugs 34
      days earlier than patients on exenatide, whereas patients using exenatide and
      vial insulin exhibited similar TTAD for all drugs. Exenatide use was estimated to
      significantly reduce medical costs of the first posttreatment year sufficient to
      offset higher prescription drug costs. These results were confirmed using
      propensity score matching estimation and were robust across episode type.
      CONCLUSIONS: Patients initiating drug therapy using exenatide might incur lower
      posttreatment costs than similar patients who initiated treatment using insulin.

PMID- 22464690
TI  - Helminthic therapy: improving mucosal barrier function.
AB  - The epidemiology of autoimmune diseases and helminth infections led to
      suggestions that helminths could improve inflammatory conditions, which was then
      tested using animal models. This has translated to clinical investigations aimed
      at the safe and controlled reintroduction of helminthic exposure to patients
      suffering from autoimmune diseases (so-called 'helminthic therapy') in an effort
      to mitigate the inflammatory response. In this review, we summarize the results
      of recent clinical trials of helminthic therapy, with particular attention to
      mechanisms of action. Whereas previous reviews have emphasized immune regulatory
      mechanisms activated by helminths, we propose that enhancement of mucosal barrier
      function may have an equally important role in improving conditions of
      inflammatory bowel diseases.

PMID- 22464692
TI  - The clinical implications of ABO blood groups in Pseudomonas aeruginosa sepsis in
      children.
AB  - BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) sepsis is a fetal disease with
      rapid progressive shock for infants and children in hospital and in the
      community, without initial treatment with appropriate antibiotics. Because
      underlying risk factors remain unclear for affected patients, it is still
      difficult for early diagnosis and therapy. Recently, ABO blood group antigens
      were associated with several infectious diseases. However, it was not reported
      whether the ABO blood group could be the clinical implications for pediatric
      Pseudomonas sepsis. METHODS: This study retrospectively reviewed the medical
      records of 23 infants and children with P. aeruginosa sepsis, who were
      hospitalized at Kaohsiung Chang Gung Memorial Hospital from 2003 to 2009.
      RESULTS: Eight cases had nosocomial infections, with a higher mortality rate
      (50%) than 15 cases (26.7%) in the community. Thirteen patients (86.7%) with
      community-acquired sepsis were infants, significantly younger than the nosocomial
      cases. ABO blood group antigens were known in 21 cases and B phenotype was the
      most significant. In the community-acquired group, fever and diarrhea were the
      most prevalent symptoms on initial presentation. Moreover, pneumonitis was the
      most concomitant disease in fatal cases. CONCLUSION: Blood group B was highly
      associated with pediatric P. aeruginosa sepsis. This could be a risk factor, and
      play an important role for the pathogenesis of P. aeruginosa sepsis. Furthermore,
      if a previously healthy infant with fever and diarrhea suddenly had septic
      presentation, P. aeruginosa infection should be considered. In addition, more
      intensive care could be needed for such blood group B pediatric patients, if
      pneumonitis was concomitant on admission for the high mortality rate.

PMID- 22464693
TI  - Focus groups in nursing research: methodological perspectives.
AB  - Focus groups have been increasingly used as a data collection method in nursing
      research. The key feature of focus groups is the active interaction among
      participants to explore their views and opinions. In this respect, focus groups
      are distinct from other methods such as Delphi groups, nominal groups,
      brainstorming, and consensus panels, which seek to determine a consensus between
      participants. Compared with other data collection methods, it can be concluded
      that the real strength of focus groups is not simply in exploring what
      participants have to say, but in providing insights into the sources of complex
      behaviors and motivations. The aim of this paper is to present an overview of the
      focus group as a research tool in nursing research, particularly in nursing
      education.

PMID- 22464694
TI  - The relationship between psychosocial job stress and burnout in emergency
      departments: an exploratory study.
AB  - BACKGROUND: The purpose of this study was to examine the relationship and
      predictive power of various psychosocial job stressors for the 3 dimensions of
      burnout in emergency departments. METHODS: This study was structured as a cross
      sectional design, with a questionnaire as the tool. The data were gathered using
      an anonymous questionnaire in 3 hospitals in Spain. The sample consisted of 191
      emergency departments. Burnout was evaluated by the Maslach Burnout Inventory and
      the job stressors by the Nursing Stress Scale. FINDINGS: The Burnout Model in
      this study consisted of 3 dimensions: emotional exhaustion, cynicism, and reduced
      professional efficacy. The model that predicted the emotional exhaustion
      dimension was formed by 2 variables: Excessive workload and lack of emotional
      support. These 2 variables explained 19.4% of variance in emotional exhaustion.
      Cynicism had 4 predictors that explained 25.8% of variance: Interpersonal
      conflicts, lack of social support, excessive workload, and type of contract.
      Finally, variability in reduced professional efficacy was predicted by 3
      variables: Interpersonal conflicts, lack of social support, and the type of shift
      worked, which explained 10.4% of variance. DISCUSSION: From the point of view of
      nurse leaders, organizational interventions, and the management of human
      resources, this analysis of the principal causes of burnout is particularly
      useful to select, prioritize, and implement preventive measures that will improve
      the quality of care offered to patients and the well-being of personnel.

PMID- 22464695
TI  - Neuroethical issues related to the use of brain imaging: can we and should we use
      brain imaging as a biomarker to diagnose chronic pain?

PMID- 22464696
TI  - Induced fear reduces the effectiveness of a placebo intervention on pain.
AB  - Fear was induced by the anticipation of electric shock in order to investigate
      whether fear reduced the effectiveness of a placebo intervention on reported pain
      and the acoustic startle reflex. Thirty-three subjects participated in a 3
      Condition (Natural History [NH], Placebo [P], Placebo+Fear [PF])*3 Test (Pretest,
      Posttest 1, Posttest 2) within-subject design, tested on 3 separate days.
      Measures of fear were fear of pain (FOP), measured by the Fear of Pain
      Questionnaire (FPQ-III); fear-potentiated startle; and a self-report measure that
      assessed the effectiveness of the fear induction procedure. In the pain intensity
      data, there was a trend towards a placebo effect. This trend was abolished by
      induced fear, and was most pronounced in subjects who were highest in measures of
      fear. The placebo manipulation also caused a reduction in startle reflex
      amplitude. This effect was abolished by induced fear, and was strongest amongst
      high FOP subjects. In conclusion, induced fear abolished placebo analgesia, and
      this effect was strongest in subjects who had high scores on measures of fear.

PMID- 22464697
TI  - Exploring the relationship of pain and development in the neonatal intensive care
      unit.

PMID- 22464698
TI  - [Prognosis analysis of hepatitis B virus recurrence after liver transplantation:
      a single-center study of 38 cases].
AB  - OBJECTIVE: To analyze the prognosis of hepatitis B virus (HBV) recurrence after
      liver transplantation. METHODS: Thirty-eight patients (37 males; 1 female) with
      HBV-related end-stage liver disease underwent liver transplantation at our
      institute between December 1998 and November 2009 and experienced HBV recurrence.
      Clinical data from pre-transplant and follow-up examinations were retrospectively
      retrieved from medical records, and included serologic indices of HBV (HBV DNA,
      markers of liver function) and histological findings from liver biopsy. RESULTS:
      The median follow-up time was 45.1 months. The median time to HBV recurrence
      after transplantation was 31.8 months (range: 0.3 to 72.8 months) for
      histologically benign cases and 13.7 months (range: 0.3 to 66.6 months) for
      malignant cases. HBV DNA gene mutations were detected in 21% (8/38) of cases.
      Eighteen patients were treated with entecavir or adefovir, with respect to gene
      mutations, and HBV DNA fell below 103 copies/ml and liver function became normal.
      Twenty-two patients died, and causes of death included hepatocellular carcinoma
      (HCC, n=18), organ failure (n=2), or infection (n=1). CONCLUSION: HBV gene
      mutations and HCC recurrence were important risk factors for HBV recurrence in
      our study population. In addition, patients with benign liver diseases who
      received salvage therapy with adefovir or entecavir achieved a satisfactory
      prognosis.

PMID- 22464699
TI  - [A study of the efficacy and safety of using hepatitis B surface antigen-positive
      donors for liver transplantation].
AB  - OBJECTIVE: To evaluate the outcomes of liver transplant recipients who received
      liver allografts from hepatitis B surface antigen (HBsAg)-positive donors.
      METHODS: The medical records of 23 male patients (median age, 42.5 years; range:
      29-61) who received HBsAg-(+) liver allografts in our organ transplant center
      were retrospectively analyzed. All patients had confirmed diagnosis of end-stage
      liver disease (ESLD) secondary to hepatitis B virus (HBV) infection, including 13
      HBsAg(+)/HBeAg(-)/HBcAb(+) cases and 10 HBsAg(+)/HBeAb(+)/HBcAb(+) cases. After
      transplantation, all patients were administered oral entecavir and intravenous
      anti-hepatitis B immunoglobulin (HBIG) (2000 IU/d during the first week), along
      with a steroid-free immune suppression regimen. HBV-related antigen and antibody
      and HBV DNA were detected on post-transplantation days 1, 7, 14, 21, and 30. The
      liver allografts were monitored by ultrasound imaging. After discharge, monthly
      follow-up recorded liver function, renal function, acute rejection, infections,
      vascular complications, biliary complications, HBV recurrence, cancer recurrence,
      and patient survival. RESULTS: Two of the recipients died from severe
      perioperative pneumonia. The remaining 21 recipients were followed-up for 10 to
      38 months, and all 21 patients remained HBsAg(+). One recipient developed biliary
      ischemia and required a second liver transplantation at five months after the
      primary transplantation. Three recipients (all primary) died from tumor
      recurrence at 9, 14, and 18 months post-transplantation, respectively. All other
      recipients survived and had acceptably low HBV DNA copy levels. Color Doppler
      imaging showed good graft function and normal texture. The patient and graft
      survival rates were 78.3% (18/23) and 73.9% (17/23), respectively. The recurrence
      rate of HBV infection was 100% (23/23). In surviving patients, no liver function
      abnormality, graft loss, or death was found to be related to the recurrence of
      HBV infection. CONCLUSION: Liver transplantation using HBsAg(+) liver grafts was
      safe for patients with ESLD secondary to HBV infection.

PMID- 22464700
TI  - [Evaluation of effective doses of hepatitis B immunoglobulin to eliminate
      hepatitis B surface antigen from infected neonates].
AB  - OBJECTIVE: To determine the effective dose of hepatitis B immunoglobulin (HBIG)
      for clearing maternally-transmitted hepatitis B virus (HBV) from a newborn.
      METHODS: Full-term neonates born to HBV-infected mothers were tested for
      hepatitis B surface antigen (HBsAg) and HBV DNA in venous blood, Individuals with
      positive results within two hours after birth were selected for study, and
      divided among two treatment groups: research group receiving HBIG continually
      adjusted to quantitative levels of neonatal HBsAg and HBV DNA levels; control
      group receiving standard HBIG 200IU dose. All neonates were also treated with 10
      micrograms of recombinant vaccine. The decreases in HBsAg and HBV DNA over 12
      months were comparatively analyzed between the two treatment groups. RESULTS: The
      two treatment groups (HBIG adjusted vs. standard) were statistically similar in
      Apgar score (9.38+/-0.49 vs. 9.37+/-0.48), neonate body weight (3458.67+/-374.93
      vs. 3558.61+/-322.85 g), maternal age (26.33+/-3.63 vs. 25.33+/-3.03), and
      initial HBsAg and HBV DNA levels (rank sum test Z = 1.381, and Z = 0.700,
      respectively) (all, P more than 0.05). Successful clearance of HBV infection
      within 12 months was achieved in significantly more neonates in the HBIG adjusted
      therapy group than in the standard therapy group (82.8% vs. 57.4%; x2 = 9.696, P
      less than 0.05). CONCLUSION: Adjusting the neonatal HBIG dose according to HBsAg
      and HBV DNA levels can improve the success rate of clearing maternally
      transmitted HBV.

PMID- 22464701
TI  - [Efficacy of low-dose interferon therapy for treating chronic hepatitis C
      patients who cannot tolerate standard treatment].
AB  - OBJECTIVE: To investigate the therapeutic efficacy of interferon (IFN) therapy
      and risk of long-term administration for chronic hepatitis C (CHC) patients who
      cannot tolerate the standard treatment. METHODS: Forty-six CHC patients who had
      proven intolerant to standard treatments were treated with low-dose IFN (non
      pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin
      (RBV; 0.6g to 0.9 g/d) for 72 weeks. RESULTS: Forty-three (93.5%) of the patients
      were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only
      three patients experienced severe side effects (low white blood cell and platelet
      counts) that required treatment withdrawal. The virology response rates over
      treatment time were: rapid virologic response (RVR): 10.9%; early virus response
      (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response:
      47.8%. B-sonographic imaging revealed that three patients experienced improved
      liver morphology through the treatment course. The patients who achieved RVR,
      EVR, or 24 weeks virologic response also attained higher 48 week virologic
      response. The 24 week virologic response had the strongest predictive value of
      good prognosis. CONCLUSIONS: Our study demonstrated that long-term treatment with
      low-dose interferon plus ribavirin is effective for patients who are otherwise
      intolerant to standard treatment. In these patients, low-dose IFN plus RBV can
      obtain a high virologic response rate at 48 week. Furthermore, the 24 week
      virologic response is sufficiently predictive of treatment success. As with any
      treatment regimen, it is important for healthcare workers to monitor the disease
      status and potential side effects throughout the course of therapy.

PMID- 22464702
TI  - [Tumor-infiltrating FoxP3+ Tregs are associated with CD34 expression and
      prognosis of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the correlation between FoxP3+ regulatory T lymphocytes
      (Tregs) in hepatocellular carcinomas (HCCs) and peritumoral tissues with CD34
      expression and patient prognosis. METHODS: Fifty-five sets of patient-matched
      tumors and peritumoral tissues were obtained during curative resection for HCC.
      In situ immunohistochemistry was used to assess and comparatively analyze Treg
      presence and CD34 expression in each specimen set. The relation between
      quantified Tregs values and various clinicopathologic factors were evaluated by
      the Spearman Rank Correlation test. Univariate (Log Rank test) and multivariate
      (Cox Regression model) analyses were used to determine the potential prognostic
      value of each factor. RESULTS: The average number of intratumoral Tregs was
      significantly higher than that in corresponding peritumoral tissues (10.8 (range:
      4.4 to 19.4) vs. 1.4 (0.6 to 3.2), respectively; P less than 0.01). The presence
      of intratumoral Tregs correlated with up-regulated CD34 expression (r = 0.279, P
      less than 0.05). Increased number of intratumoral Tregs were significantly
      associated with decreased rates of overall survival (OS, P less than 0.05) and
      disease-free survival (DFS, P less than 0.05), and was identified as an
      independent prognostic factor (OS, hazard ratio (HR) = 3.310, 95% confidence
      interval (CI): 1.368-8.007, P less than 0.01; DFS, HR = 2.666, 95% CI: 1.321 to
      6.394, P less than 0.01). CONCLUSION: Intratumoral infiltration by Tregs is a
      marker of poor prognosis in HCC patients.

PMID- 22464703
TI  - [Hypoxia-induced alterations of lipid metabolism in the normal human hepatic L02
      cell line].
AB  - OBJECTIVE: To investigate the effects of hypoxia on lipid metabolism in the
      normal human hepatic cell line L02 and to investigate the underlying molecular
      mechanisms. METHODS: L02 cells were exposed to hypoxic conditions (experimental
      groups: at 1% O2, 5% CO2, 94% N2 for 3, 6, 12, 24, or 48 hours) or normoxic
      conditions (control group: at 21% O2). Lipid droplet accumulation and
      triglyceride content were measured in each group by oil red O staining and
      biochemical assay, respectively. The mRNA expression levels of hypoxia-inducible
      factor (HIF)-2a and sterol regulatory element binding protein (SREBP)-1c were
      detected by reverse transcription-polymerase chain reaction. Protein expression
      levels of HIF-2a, adipose differentiation-related protein (ADRP), and Fas were
      tested by Western blot analysis. RESULTS: Lipid droplet accumulation and the
      triglyceride content were significantly higher in the hypoxia group than the
      normoxia group. In addition, the hypoxia groups had significantly down-regulated
      mRNA expression of SREBP-1c (12h: 0.236+/-0.043, 24 h: 0.287+/-0.044, 48 h:
      0.342+/-0.049 vs. normoxia: 0.503+/-0.037; F = 28.37, P less than 0.01) and FAS
      protein (12 h: 0.562+/-0.054, 24 h: 0.674+/-0.062, 48 h: 0.682+/-0.057 vs
      normoxia: 0.857+/-0.069; F = 16.08, P less than 0.01). In normoxic cells, little
      or no expression of HIF-2a protein was detected by Western blot. In hypoxic
      cells, HIF-2a protein expression peaked at 6h (0.973+/-0.067). ADRP protein
      expression was significantly higher in hypoxia groups than in the normoxia group
      (12 h: 0.319+/-0.043, 24 h: 0.732+/-0.056 and 48 h: 0.873+/-0.066 vs. 0.211+/
      0.019; all, P less than 0.05. CONCLUSION: Exposure to hypoxic conditions might
      induce lipidosis in normal human hepatic cells by stimulating HIF-2a and ADRP
      expression.

PMID- 22464704
TI  - [Role of endoplasmic reticulum stress in alcoholic liver disease-related
      hepatocyte apoptosis].
AB  - OBJECTIVE: To investigate the role of endoplasmic reticulum stress (ERS) in
      alcoholic liver disease (ALD)-related hepatocyte apoptosis. METHODS: A rat model
      of ALD was established by continuous intragastric administration of ethanol. At
      4, 8, 12, and 16 weeks later, randomly selected rats were sacrificed for serum
      and liver sample collection. Serum levels of total homocysteine (tHcy) were
      examined by chemiluminescence analysis. Cystathionine beta-synthase (CBS)
      activity in liver tissue was measured by chromatometry. The mRNA and protein
      expressions of ERS-related factors, glucose-regulated protein (GRP)-78, calpain 2
      and caspase-12, were analyzed by reverse transcription-polymerase chain reaction
      and immunohistochemistry, respectively. Hepatocyte apoptosis was detected by the
      TdT-mediated dUTP nick end labeling assay. RESULTS: At 16 weeks, the ALD rats'
      livers exhibited diffuse microvesicular adipose degeneration and fibrosis in the
      liver sinus and portal septa. As the duration of ethanol administration extended,
      the tHcy levels gradually increased (P less than 0.01), CBS activity decreased (P
      less than 0.01), gene expression levels of GRP-78, calpain 2, and caspase-12 were
      up-regulated (P less than 0.01), and protein expression levels of GRP-78 and
      calpain 2 were gradually increased. However, the protein level of procaspase-12
      was found to decrease with increased duration of ethanol administration. Finally,
      the hepatocyte apoptosis index showed an increasing trend over time (P less than
      0.01). CONCLUSION: In our experimental ALD rat model, hepatic apoptosis was
      detected with increasing frequency over the duration of ALD. Increased apoptosis
      was likely due to decreased CBS activity causing hyperhomocysteinemia, which
      further induced ERS and activated the calpain 2 and caspase-12 signaling pathway.
      These ethanol-induced molecular changes may provoke hepatic apoptosis and
      subsequently promote the pathogenic processes of alcoholic liver disease.

PMID- 22464705
TI  - [The effect of resistin on nuclear factor-kB and tumor necrosis factor-a
      expression in hepatic steatosis].
AB  - OBJECTIVE: To investigate the potential regulatory role played by the hormone
      resistin in lipid metabolism and expression of nuclear factor (NF)-kB and tumor
      necrosis factor (TNF)-a during hepatic steatosis. METHODS: A non-alcoholic fatty
      liver disease (NAFLD) cell model was established by treating the normal human
      hepatic cell line, L02, with palmitic acid. Four research groups of L02 cells
      were generated: C group (control, no palmitic acid treatment), P group (NAFLD
      model, treated with 20 microg/ml palmitic acid), CR group (C group treated with
      50 microg/L recombinant human resistin), and PR group (P group treated with 50
      microg/L recombinant human resistin). All treatments were carried out for 72
      hours. Oil red O staining was used to detect the intracellular changes in lipid
      drops. Biochemical assays were used to measure triglycerides (TGs), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl
      transpeptidase (GGT) levels in culture medium. The mRNA and protein expression
      levels of insulin receptor substrate (IRS)-2, NF-kB, and TNF-a were determined by
      reverse transcription-polymerase chain reaction and Western blot analysis,
      respectively. RESULTS: The TG, ALT, AST, and GGT levels were higher in the P, CR,
      and PR groups than in the C group. The NF-kB mRNA level was also higher in the P,
      CR, and PR groups (Student's t = 17.64, 22.03, 26.06 respectively) than in the C
      group, as was the TNFa mRNA level ( t = 5.67, 5.38, 11.64), but the IRS-2 mRNA
      level was lower ( t = 8.19, 9.23, 20.93) (all, P less than 0.05). In addition, no
      significant difference in these mRNA levels were found between the P group and
      the CR group (NF-kB: t = 1.75, TNFa: t = 0.58, IRS-2: t = 2.14; all, P more than
      0.05). The detected protein levels of NF-kB, TNFa, and IRS-2 were consistent with
      the mRNA levels. CONCLUSION: Resistin can promote steatosis in LO2 cells through
      the NF-kB signaling pathway, thereby contributing to the NAFLD pathogenic
      process.

PMID- 22464706
TI  - [New evidence of porcine endogenous retrovirus transmission with new bio
      artificial liver system: a experimental study].
AB  - OBJECTIVE: To investigate the potential transmissibility of porcine endogenous
      retrovirus (PERV) from a newly-developed porcine hepatocyte bioartificial liver
      (BAL) system prior to human clinical trial by using a live canine model. METHODS:
      Five normal beagles were treated with the new BAL support system for six hours.
      Samples of plasma from the BAL system and whole blood from the beagles were
      collected at regular intervals over the six month study period. DNA and RNA were
      isolated from both the peripheral blood mononuclear cells (PBMCs) and plasma for
      evaluation by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR,
      respectively, to detect PERV and the Sus scrofa cytochrome B normalization
      standard. In addition, RT activity and the in vitro infectivity of the plasma
      were detected in HEK293 cells. RESULTS: All five beagles remained in stable
      physical health throughout the treatment and survived until the end of the study.
      PERV RNA-positivity and RT activity were only detected in the plasma samples from
      the 3rd BAL treatment cycle. All other samples, including PBMCs and plasma, were
      negative for PERV RNA, PERV DNA, and RT activity. In addition, none of the sera
      samples showed in vitro infectivity. CONCLUSION: Application of our BAL system
      does not lead to PERV transmission.

PMID- 22464707
TI  - [Establishment of an albumin and cytokeratin 19 genetically-modified embryonic
      stem cell line and evaluation of its hepatoblast differentiation capacities].
AB  - OBJECTIVE: To establish a gene-modified embryonic stem (ES; E14.1-2) cell line
      with hepatoblast differentiation reporter genes, albumin (ALB) and cytokeratin 19
      (CK19), labeled to facilitate study of their potential applicability as
      differentiated hepatoblasts. METHODS: Two expression vectors were constructed,
      one with the ALB promotor driving the enhanced green fluorescent protein (EGFP)
      and anti-neomycin genes (pAlb-EGFP), and the other with the CK19 promotor driving
      the red fluorescence protein and anti-hygromycin genes (pCK19-hCD25-IRES
      tdTOMATO). The linearized vectors were electroporated into the E14.1 line, and
      double reporter genes-modified ES cells (E14.1-2) were selected by neomycin and
      hygromycin. E14.1-2 hepatoblast differentiation was induced by exposure to growth
      factors (BMP4 and bFGF) and evidenced by embryoid body formation. Fluorescence
      activated cell sorting (FACS) and reverse transcription-polymerase chain reaction
      (RT-PCR) were used to confirm whether differentiated cells were hepatoblast-like
      and to quantify the differentiation efficiency. RESULTS: The pAlb-EGFP and pCK19
      hCD25-IRES-tdTOMATO vectors were shown to specifically activate ALB and CK19
      expression. The E14.1-2 cell line with labeled ALB and CK19 was established, and
      shown to have pluripotency by RT-PCR detection of pluripotent markers'
      expression, namely Oct4 and SSEA-1. After 22 days of induction, 21.27% of the
      differentiated hepatoblasts were detected by FACS as positive for ALB and CK19
      expression. CONCLUSIONS: A gene-modified ES cell line was generated with
      hepatocyte differentiation reporter genes ALB and CK19 labeled. The
      differentiation of the resultant E14.1-2 line was technically simple to qualify
      and quantify, and will likely aid future studies of hepatoblast characteristics.

PMID- 22464708
TI  - Impact of endovascular simulator training on vascular surgery as a career choice
      in medical students.
AB  - OBJECTIVE: The primary goal of this study was to determine whether exposure to
      endovascular simulator training increases interest in vascular surgery among
      medical students. Secondary goals were to determine whether interest in vascular
      surgery is inversely related to the time after exposure, to identify factors
      associated with interest, and to identify students' characteristics that
      positively influence performance metrics. METHODS: This was a prospective,
      randomized, crossover study comprising 80 medical students who were randomized
      into group A (n = 40) and group B (n = 40). Participants completed a survey of
      their interest in vascular surgery and attitudinal factors using Vascular Surgery
      Interest Form (VSIF) before exposure to the simulator (pretest). At 1 month after
      exposure of group A to the simulator, both groups were tested using VSIF (test).
      Upon completion of testing, group B was exposed to simulator training, whereas
      group A received no further training. At 2 months after exposure of group B to
      the simulator, both groups were posttested using VSIF, which asked the students'
      level of interest in vascular surgery using a 1 to 10 scale. Performance metrics
      were recorded during each exposure. Differences among cohort demographics were
      determined using Pearson chi(2) analysis. Differences in interest were determined
      with paired sample correlations. Linear regression and analysis of variance were
      used to correlate VSIF responses with interest and the performance metrics.
      RESULTS: Both student cohorts had significant increases in interest after
      exposure to simulation. In group A, test interest (mean +/- standard deviation)
      was significantly higher than pretest and posttest interests (5.51 +/- 1.73 vs
      4.00 +/- 1.88 vs 4.18 +/- 1.82; P < .05). In group B, posttest interest was
      significantly higher than pretest and test interests (5.62 +/- 2.03 vs 3.96 +/-
      1.61 vs 4.08 +/- 1.64; P < .05). The increase in interest was reciprocally
      related to the time passed since the initial exposure. Resident and attending
      lifestyle, length of training, radiation concerns, gender identification of a
      mentor, and personality fit with occupation were not correlated with interest.
      Sex, medical school year, comfort with endovascular procedures, willingness to
      work long hours, interest in performing percutaneous procedures, and commitment
      to surgical career did not affect impact performance metrics. CONCLUSIONS: One
      exposure of students to endovascular simulator training is associated with an
      increase in vascular surgery interest. Acquired interest is reciprocally related
      to the time demonstrating the temporal importance of the exposure.

PMID- 22464709
TI  - Obesity, TV commercials, passive commuting, and smoking.

PMID- 22464710
TI  - Our responsibility for medical radiation dose determinations.

PMID- 22464711
TI  - Thoracic endovascular aortic repair for retrograde type A aortic dissection with
      an entry tear in the descending aorta.
AB  - PURPOSE: To report the immediate and follow-up outcome of thoracic endovascular
      aortic repair (TEVAR) in highly selected patients with retrograde type A aortic
      dissection (RAAD) and an entry tear in the descending aorta. MATERIALS AND
      METHODS: TEVAR was performed in 17 patients with RAAD and an entry tear in the
      descending aorta. None of the patients had severe aortic regurgitation, cardiac
      tamponade, coronary artery involvement, or brain ischemia. The false lumen in the
      ascending aorta was patent in nine patients. Two patients had acute malperfusion
      of the branched artery. Computed tomography (CT) was performed 14 days, 3 months,
      and 6 months after the intervention and annually thereafter. RESULTS: All
      procedures were technically successful, with complete coverage of the entry tear
      and complete thrombosis of the false lumen in the ascending aorta. All patients
      survived through the follow-up period (25.7 months +/- 17.2). TEVAR resulted in
      thrombosis of the false lumen, reabsorption of the false lumen thrombus, and
      enlargement of the true lumen. The mean maximal diameter of the ascending aorta
      and the false lumen in the ascending aorta significantly decreased after TEVAR.
      At the distal edge of the stent graft, the mean diameter of the descending aorta
      and the false lumen markedly decreased after TEVAR. Complete thrombosis of the
      false lumen was observed at the distal edge of the stent graft in 16 (94.1%)
      patients and at the diaphragmatic level in 9 (52.9%) patients. CONCLUSIONS: TEVAR
      for RAAD with an entry tear in the descending aorta is a safe and effective
      technique in highly selected patients.

PMID- 22464712
TI  - Salvage of angioplasty failures and complications in hemodialysis arteriovenous
      access using the FLUENCY Plus Stent Graft: technical and 180-day patency results.
AB  - PURPOSE: To review technical and 180-day clinical outcomes when stent grafts were
      used to treat dysfunctional arteriovenous (AV) hemodialysis access circuits.
      MATERIALS AND METHODS: The FLUENCY Plus Stent Graft (Bard Peripheral Vascular,
      Tempe, Arizona) was used to salvage percutaneous transluminal angioplasty (PTA)
      technical failures and complications in AV access circuits over 2 years. There
      were 106 patients treated with 138 stent grafts. Indications for stent graft use
      included residual stenosis after PTA (n = 81), extravasation after PTA (n = 22),
      early recurrent stenosis (n = 14), pseudoaneurysms (n = 4), and "other" (n = 4).
      Data were retrospectively analyzed for complications and outcomes. RESULTS:
      Technical success was achieved in all patients, and clinical success was achieved
      in 104 (98%) of 106 patients. At 180 days, postintervention primary patency
      (PIPP) was 47%, and postintervention secondary patency (PISP) was 79%. PIPP was
      62% for autogenous fistulas (AVFs) and 35% for prosthetic grafts (AVGs) (P =
      .010). The 180-day PIPP for stent grafts 9-10 mm in diameter was 63% versus 38%
      for stent grafts 6-8 mm in diameter (P = .012). Implants that did not cross the
      elbow had a 180-day PIPP of 47% compared with 25% for implants across the elbow
      (P = .032). Technical complications were periprocedure AVG thromboses (n = 2),
      intraprocedural stent graft dislodgment (n = 1), venospasm (n = 2), and contrast
      agent-related hives (n = 1). One patient returned at 2 months with an infected
      AVG and stent graft in the outflow vein. CONCLUSIONS: The FLUENCY Plus Stent
      Graft was effective for maintenance of hemodialysis access circuit patency and
      was comparable or better than historical outcomes for PTA and bare stents.
      Factors that favored improved patency included larger diameter devices, use in
      AVFs, and avoiding placement across the elbow joint.

PMID- 22464713
TI  - Applying a structured innovation process to interventional radiology: a single
      center experience.
AB  - PURPOSE: To determine the feasibility and efficacy of applying an established
      innovation process to an active academic interventional radiology (IR) practice.
      MATERIALS AND METHODS: The Stanford Biodesign Medical Technology Innovation
      Process was used as the innovation template. Over a 4-month period, seven IR
      faculty and four IR fellow physicians recorded observations. These observations
      were converted into need statements. One particular need relating to gastrostomy
      tubes was diligently screened and was the subject of a single formal
      brainstorming session. RESULTS: Investigators collected 82 observations, 34 by
      faculty and 48 by fellows. The categories that generated the most observations
      were enteral feeding (n = 9, 11%), biopsy (n = 8, 10%), chest tubes (n = 6, 7%),
      chemoembolization and radioembolization (n = 6, 7%), and biliary interventions (n
      = 5, 6%). The output from the screening on the gastrostomy tube need was a
      specification sheet that served as a guidance document for the subsequent
      brainstorming session. The brainstorming session produced 10 concepts under three
      separate categories. CONCLUSIONS: This formalized innovation process generated
      numerous observations and ultimately 10 concepts to potentially to solve a
      significant clinical need, suggesting that a structured process can help guide an
      IR practice interested in medical innovation.

PMID- 22464714
TI  - Where good ideas come from: where the wild things are!

PMID- 22464715
TI  - Long-term outcomes of stent placement for symptomatic nonthrombotic iliac vein
      compression lesions in chronic venous disease.

PMID- 22464716
TI  - Doctor, would you drain this collection?

PMID- 22464717
TI  - Safety and efficacy of primary metallic biliary stent placement with tract
      embolization in patients with massive ascites: a retrospective analysis of 16
      patients.
AB  - PURPOSE: To evaluate the safety and efficacy of primary metallic biliary stent
      placement with tract embolization in patients with massive ascites. MATERIALS AND
      METHODS: Sixteen patients with malignant biliary obstruction and massive ascites
      (age range, 44-79 y; median age, 59 y) were treated with primary percutaneous
      stent placement with tract embolization. These patients were unsuitable
      candidates for endoscopic intervention. Etiologies of biliary obstruction were
      gastric cancer with hilar nodal metastases (n = 9), pancreatic carcinoma (n = 5),
      cholangiocarcinoma (n = 1), and gallbladder carcinoma (n = 1). Eight patients had
      nonhilar lesions and the remaining eight had hilar lesions. Percutaneous accesses
      to the biliary system and stent placements were performed in a one-step
      procedure, and catheters were removed with tract embolization with metallic
      coils. RESULTS: Stent placement and tract embolization were successful in all
      patients, without external drainage catheters left in place. Significant
      reduction of serum bilirubin level was observed in 14 patients (87.5%). No bile
      peritonitis or intraperitoneal hemorrhage occurred. Major complications included
      postprocedural cholangitis (12.5%), bloody bowel discharge (6.2%), and right
      pleural effusion (25.0%). One patient who died 19 days after intervention was
      deemed to represent a procedure-related mortality. During the survival period
      (range, 19-175 d; median, 66 d), stent occlusion was noted in two patients at 6
      and 159 days after the procedure. Primary stent patency was achieved in 14
      patients (87.5%). CONCLUSIONS: Primary biliary stent placement with tract
      embolization is technically safe and offers an effective palliative treatment
      option for patients with malignant biliary obstruction and massive ascites when
      endoscopic intervention is not possible.

PMID- 22464718
TI  - Transjugular intrahepatic portosystemic shunt occlusion via modified pringle
      maneuver for radiofrequency ablation of nearby tumor.

PMID- 22464719
TI  - Transvenous creation of a mesocaval shunt: report of use in the management of
      extrahepatic portal vein occlusion.

PMID- 22464720
TI  - Percutaneous removal of a dropped appendicolith using a basket retrieval device
      and concomitant abscess drainage.

PMID- 22464721
TI  - A graphic look at massive fibroid expulsion following uterine artery
      embolization.

PMID- 22464722
TI  - Prospective diagnosis of corona mortis hemorrhage in pelvic trauma.

PMID- 22464723
TI  - Early endovascular salvage of a bovine pericardial superior vena cava graft.

PMID- 22464724
TI  - Transportation characteristics of embolic microparticles.

PMID- 22464726
TI  - Cortical-basal ganglia imbalance in schizophrenia patients and unaffected first
      degree relatives.
AB  - Structural brain changes are amongst the most robust biological alterations in
      schizophrenia, and their investigation in unaffected relatives is important for
      an assessment of the contribution of genetic factors. In this cross-sectional
      morphometry study we investigated whether volume changes in SZ are linked with
      genetic vulnerability and whether these effects are separated from secondary
      illness effects. We compared density of grey and white matter using high
      resolution 3D-anatomical MRI imaging data in 31 SZ patients, 29 first-degree
      relatives and 38 matched healthy controls, using Voxel-Based Morphometry (VBM)
      with SPM8. Volume of basal ganglia was also compared by manual segmentation. We
      found increased grey matter in the striatum, globus pallidus internus and
      thalamus and decreased grey matter in the parahippocampal and cingulate gyri both
      in SZ patients and relatives. Additionally, SZ patients had decreased volume of
      temporal, frontal and limbic grey and white matter in comparison with relatives
      and controls. Relatives showed intermediate values in many of these areas.
      Increased volume in the thalamus and parts of the basal ganglia and decreased
      volume of cortical areas and underlying white matter were thus associated with
      schizophrenia and its genetic vulnerability. These results suggest that brain
      morphological changes associated with SZ are in part determined by genetic risk
      factors and are not entirely explained by effects of medication or changes
      secondary to illness.

PMID- 22464727
TI  - High frequency repetitive transcranial magnetic stimulation reduces tobacco
      craving in schizophrenia.

PMID- 22464728
TI  - Training of affect recognition (TAR) in schizophrenia--impact on functional
      outcome.
AB  - Deficits in facial affect recognition as one aspect of social cognitive deficits
      are treatment targets to improve functional outcome in schizophrenia. According
      to preliminary results antipsychotics alone show little effects on affect
      recognition. A few randomized intervention studies have evaluated special
      psychosocial treatment programs on social cognition. In this study, the effects
      of a computer-based training of affect recognition were investigated as well as
      its impact on facial affect recognition and functional outcome, particularly on
      patients' quality of life. Forty clinically stabilized schizophrenic patients
      were randomized to a six-week training on affect recognition (TAR) or treatment
      as usual including occupational therapy (TAU) and completed pre- and post
      treatment assessments of emotion recognition, cognition, quality of life and
      clinical symptoms. Between pre- and post treatment, the TAR group achieved
      significant improvements in facial affect recognition, in particular in
      recognizing sad faces and, in addition, in the quality of life domain social
      relationship. These changes were not found in the TAU group. Furthermore, the TAR
      training contributes to enhancing some aspects of cognitive functioning and
      negative symptoms. These improvements in facial affect recognition and quality of
      life were independent of changes in clinical symptoms and general cognitive
      functions. The findings support the efficacy of an affect recognition training
      for patients with schizophrenia and the generalization to social relationship.
      Further development is needed in the impact of a psychosocial intervention in
      other aspects of social cognition and functional outcome.

PMID- 22464729
TI  - Molecular screening of nematodes in lacertid lizards from the Iberian Peninsula
      and Balearic Islands using 18S rRNA sequences.
AB  - The development of molecular methods is becoming a promising field in the
      analysis of parasite fauna in wildlife species. This is especially useful in the
      case of parasite species where developmental larval stages are difficult to
      assess using standard methods. In this study we screened for the presence of
      parasitic nematodes infecting lacertid lizards from the Iberian Peninsula and
      Balearic islands using nematode-specific 18S ribosomal RNA gene primers on host
      tissue samples. Sequencing of positive samples revealed the presence of different
      genera of nematodes. The detection of Strongyloides, a monoxenous genus reported
      for the first time in Podarcis lilfordi is probably the result of the
      amplification of larval stages present in the host circulatory system. Two
      spirurid nematodes, Synhimantus and a new unidentified clade, were also found,
      suggesting that reptiles might be paratenic hosts of several spirurid species.
      This study demonstrates the benefits of using specific molecular markers on
      tissue samples to identify infecting larval stages of nematodes, otherwise
      difficult to assess using traditional screening methods.

PMID- 22464730
TI  - The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase.
AB  - RanBP2/Nup358 is an essential protein with roles in nuclear transport and
      mitosis, and is one of the few known SUMO E3 ligases. However, why RanBP2
      functions in vivo has been unclear: throughout the cell cycle it stably interacts
      with RanGAP1*SUMO1 and Ubc9, whose binding sites overlap with the E3 ligase
      region. Here we show that cellular RanBP2 is quantitatively associated with
      RanGAP1, indicating that complexed rather than free RanBP2 is the relevant E3
      ligase. Biochemical reconstitution of the RanBP2/RanGAP1*SUMO1/Ubc9 complex
      enabled us to characterize its activity on the endogenous substrate Borealin. We
      find that the complex is a composite E3 ligase rather than an E2-E3 complex, and
      demonstrate that complex formation induces activation of a catalytic site that
      shows no activity in free RanBP2. Our findings provide insights into the
      mechanism of an important E3 ligase, and extend the concept of multisubunit E3
      ligases from ubiquitin to the SUMO field.

PMID- 22464732
TI  - Nucleosome organization affects the sensitivity of gene expression to promoter
      mutations.
AB  - Gene expression diverges rapidly between related species, playing a key role in
      the evolution of new phenotypes. The extent of divergence differs greatly between
      genes and is correlated to promoter nucleosome organization. We hypothesized that
      this may be partially explained by differential sensitivity of expression to
      mutations in the promoter region. We measured the sensitivity of 22 yeast
      promoters with varying nucleosome patterns to random mutations in sequence.
      Mutation sensitivity differed by up to 10-fold between promoters. This difference
      could not be explained by the abundance of transcription factor binding sites.
      Rather, mutation sensitivity positively correlated with the relative occupancy of
      nucleosomes at the proximal promoter region. Furthermore, mutation sensitivity
      was reduced upon introduction of a binding site for Reb1, a factor that blocks
      nucleosome formation, suggesting that nucleosome organization directly regulates
      mutation sensitivity. Our study suggests an important role for chromatin
      structure in the evolution of gene expression.

PMID- 22464731
TI  - Skp2 E3 ligase integrates ATM activation and homologous recombination repair by
      ubiquitinating NBS1.
AB  - The Mre11/Rad50/NBS1 (MRN) complex is thought to be a critical sensor that
      detects damaged DNA and recruits ATM to DNA foci for activation. However, it
      remains to be established how the MRN complex regulates ATM recruitment to the
      DNA foci during DNA double-strand breaks (DSBs). Here we show that Skp2 E3 ligase
      is a key component for the MRN complex-mediated ATM activation in response to
      DSBs. Skp2 interacts with NBS1 and triggers K63-linked ubiquitination of NBS1
      upon DSBs, which is critical for the interaction of NBS1 with ATM, thereby
      facilitating ATM recruitment to the DNA foci for activation. Finally, we show
      that Skp2 deficiency exhibits a defect in homologous recombination (HR) repair,
      thereby increasing IR sensitivity. Our results provide molecular insights into
      how Skp2 and the MRN complex coordinate to activate ATM, and identify Skp2
      mediatetd NBS1 ubiquitination as a vital event for ATM activation in response to
      DNA damage.

PMID- 22464733
TI  - Inflammasome-activated caspase 7 cleaves PARP1 to enhance the expression of a
      subset of NF-kappaB target genes.
AB  - Caspase 1 is part of the inflammasome, which is assembled upon pathogen
      recognition, while caspases 3 and/or 7 are mediators of apoptotic and
      nonapoptotic functions. PARP1 cleavage is a hallmark of apoptosis yet not
      essential, suggesting it has another physiological role. Here we show that after
      LPS stimulation, caspase 7 is activated by caspase 1, translocates to the
      nucleus, and cleaves PARP1 at the promoters of a subset of NF-kappaB target genes
      negatively regulated by PARP1. Mutating the PARP1 cleavage site D214 renders
      PARP1 uncleavable and inhibits PARP1 release from chromatin and chromatin
      decondensation, thereby restraining the expression of cleavage-dependent NF
      kappaB target genes. These findings propose an apoptosis-independent regulatory
      role for caspase 7-mediated PARP1 cleavage in proinflammatory gene expression and
      provide insight into inflammasome signaling.

PMID- 22464734
TI  - Close encounters of the RNF8th kind: when chromatin meets DNA repair.
AB  - Cells counteract the adverse effects of chromosome breakage by activating the DNA
      damage response (DDR), which entails a coordinated series of events that regulate
      cell cycle progression and repair of DNA lesions. The packaging of genomic DNA
      into condensed, often inaccessible chromatin severely complicates efficient DNA
      damage repair in living cells. Recent studies implicate a large number of
      chromatin-modifying enzymes in the DDR, suggesting a stepwise model in which
      chromatin is continually reconfigured to accommodate the association and action
      of repair factors during the different stages of the DDR. Emerging evidence
      suggests that the histone ubiquitin ligases RNF8/RNF168 act in concert with ATP
      dependent chromatin remodelling enzymes to orchestrate the signalling and repair
      of DNA lesions in specific chromatin topologies.

PMID- 22464735
TI  - Structure, function and regulation of spliceosomal RNA helicases.
AB  - Pre-mRNA splicing requires the activities of several ATPases from the DEAH-box,
      DEAD-box and Ski2-like helicase families to control conformational rearrangements
      within the spliceosome. Recent findings indicate that several spliceosomal
      helicases can act at multiple stages of the splicing reaction, and information on
      how those multiple actions are controlled are emerging. The recently solved
      crystal structure of the DEAH-box helicase Prp43 provides novel insights into the
      similarities and differences between the three helicase families. Here we discuss
      the potential family-specific mechanisms of spliceosomal RNA helicases and their
      regulation.

PMID- 22464736
TI  - Mycobacterium tuberculosis WhiB1 represses transcription of the essential
      chaperonin GroEL2.
AB  - A central feature of TB pathogenesis is the formation of Mycobacterium
      tuberculosis latent infections that can persist for decades. Nitric oxide
      produced by infected lung macrophages promotes expression of genes associated
      with dormancy, and impaired nitric oxide production can lead to reactivation of
      latent disease. Recently, WhiB1 was identified as a nitric oxide-responsive
      transcription factor. Here it is shown that apo-WhiB1 binds to groEL2 (Rv0440)
      promoter DNA. Apo-WhiB1 inhibited transcription from the groEL2 promoter in vitro
      and the transcript start was located ~181 bases upstream of the groEL2 start
      codon. Electrophoretic mobility shift assays with sub-fragments of the groEL2
      promoter indicated that the complete Rv0439c-Rv0440 intergenic region was
      required for WhiB1 binding, suggesting that this region possessed more than one
      WhiB1-binding site. DNase I footprinting identified a WhiB1-binding region that
      overlapped the -35 element of the groEL2 promoter. The CRP-family transcription
      factor Cmr (Rv1675c) was shown to bind the groEL2 promoter and activate
      transcription in vitro in the presence or absence of cAMP. Therefore, it is
      suggested that WhiB1 acts to oppose Cmr-mediated cAMP-independent activation of
      groEL2 expression in the presence of nitric oxide by promoter occlusion.

PMID- 22464737
TI  - To what extent can multimorbidity be viewed as a determinant of postural control
      in stroke patients?
AB  - OBJECTIVE: To investigate the determinants of postural imbalance after stroke in
      geriatric patients admitted for low-intensity rehabilitation in skilled nursing
      facilities (SNFs), particularly the role of multimorbidity. DESIGN: Cross
      sectional study design. SETTING: Fifteen SNFs. PARTICIPANTS: All patients who
      were admitted for rehabilitation after stroke in one of the participating SNFs
      (N=378) were eligible. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      Berg Balance Scale (BBS) was selected as a measure of standing balance and the
      Functional Ambulation Categories (FAC) as a measure of walking balance. RESULTS:
      Multimorbidity was present in 34% of the patients. The patients with
      multimorbidity differed from the patients without multimorbidity with respect to
      age, proprioception, and vibration sense, but not for any of the cognitive tests,
      muscle strength, or sitting balance. Patients with multimorbidity had, on
      average, lower scores on both outcome measures. In linear regression analyses,
      both the BBS and FAC were best explained by multimorbidity, muscle strength, and
      the interaction between muscle strength and static sitting balance (overall
      explained variance 66% and 67%, respectively), while proprioception added only to
      the variance of the FAC. CONCLUSIONS: Multimorbidity was independently related to
      postural imbalance after stroke in patients admitted for rehabilitation in SNFs.
      Muscle strength and the interaction of muscle strength with static sitting
      balance were important determinants of both standing and walking balance,
      indicating these factors as essential targets for rehabilitation.

PMID- 22464738
TI  - The strength of the ankle dorsiflexors has a significant contribution to walking
      speed in people who can walk independently after stroke: an observational study.
AB  - OBJECTIVE: To investigate the relationship between the strength of muscles of the
      affected lower limb and walking speed after stroke. DESIGN: A cross-sectional
      observational study. SETTING: University laboratory. PARTICIPANTS: Stroke
      survivors (N=60; mean age +/- SD, 69+/-11y) 1 to 6 years poststroke, able to walk
      10m independently without aids. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Maximum isometric strength of 12 muscle groups (hip flexors/extensors,
      adductors/abductors, internal/external rotators, knee flexors/extensors, ankle
      dorsiflexors/plantarflexors, invertors/evertors) of the affected lower limb was
      measured using hand-held dynamometry. Comfortable walking speed was measured
      using the ten-meter walk test. RESULTS: Univariate analysis revealed that
      strength of the hip flexors (r=.35, P=.01), hip extensors (r=.29, P=.03), hip
      internal rotators (r=.30, P=.02), hip adductors (r=.29, P=.03), knee extensors
      (r=.27, P=.03), knee flexors (r=.30, P=.02), ankle dorsiflexors (r=.50, P=.00),
      ankle plantarflexors (r=.29, P=.03), and ankle evertors (r=.33, P=.01) were all
      positively associated with walking speed. Multivariate analysis (n=58) revealed
      that the combined strength of the ankle dorsiflexors and the hip flexors
      accounted for 34% of the variance in walking speed (P<.001). The ankle
      dorsiflexors accounted for 31% of the variance (P<.001). CONCLUSIONS: The
      strength of muscle groups other than the lower limb extensors, particularly the
      ankle dorsiflexors, has an important role in determining walking speed after
      stroke.

PMID- 22464739
TI  - Incremental ability of needle electromyography to detect radiculopathy in
      patients with radiating low back pain using different diagnostic criteria.
AB  - OBJECTIVE: To determine the incremental ability of different needle
      electromyography diagnostic criteria to detect lumbar radiculopathy. DESIGN:
      Blinded cross-sectional study. SETTING: University hospital. PARTICIPANTS:
      Subjects aged 55 to 80 years with radiating low back pain (n=48; mean age +/- SD,
      67.9+/-7.3y) and who were asymptomatic (n=30; mean age +/- SD, 65.4+/-8y).
      INTERVENTIONS: Electrodiagnostic evaluation by a blinded electromyographer. A
      monopolar needle was used to evaluate 5 leg muscles and the lumbar paraspinal
      muscles. MAIN OUTCOME MEASURES: Presence or absence of radiculopathy using
      different electrodiagnostic criteria. RESULTS: When only positive sharp waves or
      fibrillations were considered, and at least 2 muscles innervated by the same root
      level and different peripheral nerves were counted as abnormal, 27.1% (13/48) of
      participants had positive results for radiculopathy. When at least 30% motor unit
      action potential changes in the limb muscles were also considered, participants
      with positive results increased to 45.8% (22/48), which was significant when
      compared with the first criterion (P=.002). When the mini-paraspinal mapping
      (MiniPM) test as well as at least a 30% motor unit cutoff was used, participants
      with positive results increased to 50% (24/48), which was significant when
      compared with the first criterion (P=.001). CONCLUSIONS: In addition to the
      presence of positive sharp waves or fibrillations, considering greater than or
      equal to 30% motor unit action unit potential changes as well as the MiniPM score
      maintains good specificity and improves the ability of the needle
      electromyography study to detect lumbar radiculopathy in subjects with radiating
      low back pain.

PMID- 22464740
TI  - The Rivermead Mobility Index allows valid comparisons between subgroups of
      patients undergoing rehabilitation after stroke who differ with respect to age,
      sex, or side of lesion.
AB  - OBJECTIVE: To investigate differential item functioning or item bias of the
      Rivermead Mobility Index (RMI) and its impact on the drawing of valid comparisons
      with the RMI between subgroups of patients after stroke who differ with respect
      to age, sex, or side of lesion. DESIGN: Cross-sectional study. SETTING: A
      rehabilitation center in the Netherlands and 2 stroke rehabilitation units and
      the wider community in the United Kingdom. PARTICIPANTS: The RMI was completed
      for patients undergoing rehabilitation after stroke (N=620; mean age +/- SD,
      69.2+/-12.5y; 297 [48%] men; 269 [43%] right hemisphere lesion, and 304 [49%]
      left hemisphere lesion). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Mokken scale analysis was used to investigate differential item functioning of
      the RMI between subgroups of patients who differed with respect to age (young vs
      older), sex (men vs women), and side of stroke lesion (right vs left hemisphere).
      RESULTS: No differential item functioning was found for any of the comparison
      subgroups. CONCLUSIONS: The RMI allows valid comparisons to be made between
      subgroups of patients undergoing rehabilitation after stroke who differ with
      respect to age, sex, or side of lesion.

PMID- 22464741
TI  - Item hierarchy-based analysis of the Rivermead Mobility Index resulted in
      improved interpretation and enabled faster scoring in patients undergoing
      rehabilitation after stroke.
AB  - OBJECTIVE: To enable improved interpretation of the total score and faster
      scoring of the Rivermead Mobility Index (RMI) by studying item ordering or
      hierarchy and formulating start-and-stop rules in patients after stroke. DESIGN:
      Cohort study. SETTING: Rehabilitation center in the Netherlands; stroke
      rehabilitation units and the community in the United Kingdom. PARTICIPANTS: Item
      hierarchy of the RMI was studied in an initial group of patients (n=620; mean age
      +/- SD, 69.2+/-12.5y; 297 [48%] men; 304 [49%] left hemisphere lesion, and 269
      [43%] right hemisphere lesion), and the adequacy of the item hierarchy-based
      start-and-stop rules was checked in a second group of patients (n=237; mean age
      +/- SD, 60.0+/-11.3y; 139 [59%] men; 103 [44%] left hemisphere lesion, and 93
      [39%] right hemisphere lesion) undergoing rehabilitation after stroke.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mokken scale analysis was
      used to investigate the fit of the double monotonicity model, indicating
      hierarchical item ordering. The percentages of patients with a difference between
      the RMI total score and the scores based on the start-and-stop rules were
      calculated to check the adequacy of these rules. RESULTS: The RMI had good fit of
      the double monotonicity model (coefficient H(T)=.87). The interpretation of the
      total score improved. Item hierarchy-based start-and-stop rules were formulated.
      The percentages of patients with a difference between the RMI total score and the
      score based on the recommended start-and-stop rules were 3% and 5%, respectively.
      Ten of the original 15 items had to be scored after applying the start-and-stop
      rules. CONCLUSIONS: Item hierarchy was established, enabling improved
      interpretation and faster scoring of the RMI.

PMID- 22464742
TI  - Improvement of optical trapping effect by using the focused high-order Laguerre
      Gaussian beams.
AB  - We investigate the optical trapping effect of high-order Laguerre-Gaussian (LG)
      beams acting on a dielectric sphere in Rayleigh regime. For LG beams with the
      azimuthal mode index l=0, it is found that under the same input power, the
      transverse trapping effect can be enhanced several times with increasing the
      radial mode index p, compared with that of the Gaussian beam; while its axial
      trapping effect is exactly the same as that of Gaussian beam, although the
      central trapping region reduces as p increases. For LG beams with l>=1, we find
      that the maximal transverse gradient forces increase with the increasing of p and
      the axial radiation forces reduces slightly, therefore an optimal choose on p and
      l is necessary for obtaining an optimal optical guiding. Our result is useful for
      analyzing the trapping efficiency of LG beams applied in micromanipulation
      technologies.

PMID- 22464743
TI  - AFM imaging of fenestrated liver sinusoidal endothelial cells.
AB  - Each microscope with its dedicated sample preparation technique provides the
      investigator with a specific set of data giving an instrument-determined (or
      restricted) insight into the structure and function of a tissue, a cell or parts
      thereof. Stepwise improvements in existing techniques, both instrumental and
      preparative, can sometimes cross barriers in resolution and image quality. Of
      course, investigators get really excited when completely new principles of
      microscopy and imaging are offered in promising new instruments, such as the AFM.
      The present paper summarizes a first phase of studies on the thin endothelial
      cells of the liver. It describes the preparation-dependent differences in AFM
      imaging of these cells after isolation. Special point of interest concerned the
      dynamics of the fenestrae, thought to filter lipid-carrying particles during
      their transport from the blood to the liver cells. It also describes the attempts
      to image the details of these cells when alive in cell cultures. It explains what
      physical conditions, mainly contributed to the scanning stylus, are thought to
      play a part in the limitations in imaging these cells. The AFM also offers
      promising specifications to those interested in cell surface details, such as
      membrane-associated structures, receptors, coated pits, cellular junctions and
      molecular aggregations or domains. The AFM also offers nano-manipulation
      possibilities, strengths and elasticity measurements, force interactions,
      affinity measurements, stiffness and other physical aspects of membranes and
      cytoskeleton. The potential for molecular approaches is there. New developments
      in cantilever construction and computer software promise to bring real time video
      imaging to the AFM. Home made accessories for the first generation of AFM are now
      commodities in commercial instruments and make the life of the AFM microscopist
      easier. Also, the combination of different microscopies, such as AFM and TEM, or
      AFM and SEM find their way to the market allowing comfortable correlative
      microscopy.

PMID- 22464744
TI  - [The decline of the article].

PMID- 22464745
TI  - The oral disposition index: a valuable estimate of beta-cell function in obese
      youth.

PMID- 22464746
TI  - [Management of hot flushes for breast cancer survivors].
AB  - Hot flushes experienced by breast cancer survivors present specific issues due to
      their frequency, severity and difficulty to treat. After an evaluation of her
      symptoms and expression of her expectations and requests, each patient will be
      provided a clear, synthetic, comprehensible, supported and prioritized view of
      all treatment options. Any prescribed treatment will be a shared medical decision
      making. An algorithm of treatment propositions, documented by evidence-based
      medicine, is proposed. As randomized trials show that placebo-induced reduction
      of hot flushes frequency represents to 25 to 75%, non-pharmacological approaches
      selected by the patient should be preferred at first, to the exception however of
      phytoestrogens. The first-line treatment for severe hot flushes should be,
      depending on each specific context, venlafaxine, paroxetine or gabapentine. In
      case of inefficiency, treatments of second- and third-line will be proposed.
      Prescription of progestin or of a menopausal hormone therapy should remain
      exceptional and limited to cases where all other treatments failed, after
      obtaining the patient's informed consent following exhaustive information.
      Indications of stellate ganglion block remain to be defined.

PMID- 22464747
TI  - [Ectopic decidua: variability of presentation in pregnancy and differential
      diagnoses].
AB  - The ectopic decidua is a common occurrence during pregnancy, corresponding to the
      presence of decidual tissue outside the endometrium. The pathophysiology of these
      lesions is not yet fully elucidated. The phenomenon is most often benign, with a
      favourable outcome in the post-partum and without follow-up. Because of the wide
      range of clinical presentations, from localized peritoneal granulation to large
      pelvic mass, the clinical diagnosis of ectopic decidua is difficult. Furthermore,
      imaging is not specific. The discovery of such lesions should lead to the
      realization of systematic biopsies for histological examination and rule out
      other causes such as lesions of tuberculosis or carcinomatosis.
      Immunohistochemical studies are helpful in differentiating deciduosis from
      malignant deciduoid mesothelioma, its main differential diagnosis with a
      catastrophic prognosis.

PMID- 22464748
TI  - Evaluating health inequity interventions: applying a contextual (external)
      validity framework to programs funded by the Canadian Health Services Research
      Foundation.
AB  - Including context in the measurement and evaluation of health in equity
      interventions is critical to understanding how events that occur in an
      intervention's environment might contribute to or impede its success. This study
      adapted and piloted a contextual validity assessment framework on a selection of
      health inequity-related programs funded by the Canadian Health Services Research
      Foundation (CHSRF) between 1998 and 2006. The two overarching objectives of this
      study were (1) to determine the relative amount and quality of attention given to
      conceptualizing, measuring and validating context within CHSRF funded research
      final reports related to health-inequity; and (2) to contribute evaluative
      evidence towards the incorporation of context into the assessment and measurement
      of health inequity interventions. The study found that of the 42/146 CHSRF
      programs and projects, judged to be related to health inequity 20 adequately
      reported on the conceptualization, measurement and validation of context. Amongst
      these health-inequity related project reports, greatest emphasis was placed on
      describing the socio-political and economical context over actually measuring and
      validating contextual evidence. Applying a contextual validity assessment
      framework was useful for distinguishing between the descriptive (conceptual)
      versus empirical (measurement and validation) inclusion of documented contextual
      evidence. Although contextual validity measurement frameworks needs further
      development, this study contributes insight into identifying funded research
      related to health inequities and preliminary criteria for assessing interventions
      targeted at specific populations and jurisdictions. This study also feeds a
      larger critical dialogue (albeit beyond the scope of this study) regarding the
      relevance and utility of using evaluative techniques for understanding how
      specific external conditions support or impede the successful implementation of
      health inequity interventions.

PMID- 22464749
TI  - SARAF inactivates the store operated calcium entry machinery to prevent excess
      calcium refilling.
AB  - Store operated calcium entry (SOCE) is a principal cellular process by which
      cells regulate basal calcium, refill intracellular Ca(2+) stores, and execute a
      wide range of specialized activities. STIM and Orai proteins have been identified
      as the essential components enabling the reconstitution of Ca(2+) release
      activated Ca(2+) (CRAC) channels that mediate SOCE. Here, we report the molecular
      identification of SARAF as a negative regulator of SOCE. Using heterologous
      expression, RNAi-mediated silencing and site directed mutagenesis combined with
      electrophysiological, biochemical and imaging techniques we show that SARAF is an
      endoplasmic reticulum membrane resident protein that associates with STIM to
      facilitate slow Ca(2+)-dependent inactivation of SOCE. SARAF plays a key role in
      shaping cytosolic Ca(2+) signals and determining the content of the major
      intracellular Ca(2+) stores, a role that is likely to be important in protecting
      cells from Ca(2+) overfilling.

PMID- 22464750
TI  - Prognostic factors for amputation in severe burn patients.
AB  - INTRODUCTION: Amputation is a rare procedure among burned patients. However, it
      has significant physical and psychological consequences which impact quality of
      life. OBJECTIVE: To study the incidence, etiology and prognostic factors
      associated with amputation among burned patients in Chile. METHODS: Cohort study
      of patients admitted to the Reference Burn Center of Chile from 2006 to 2011.
      Association of demographic, event and injury variables with the likelihood of
      amputation were evaluated by using multivariable analysis. RESULTS: Amputation
      incidence was 5.8% in 1090 admitted patients. Male amputee patients were
      significantly more frequent (p=0.01), with more electrical and high voltage burns
      (p<0.01) and had greater frequency of impaired consciousness (p=0.03).
      Multivariable analysis identified electrical burns (OR 13.7; 95% CI 6.7-28.1) and
      impaired consciousness (OR 2.8; 95% CI 1.4-5.7) as prognostic factors for
      amputation. CONCLUSION: Amputation is a low incidence procedure among burned
      patients. Patients who underwent amputations are frequently at working age.
      Patients with high-voltage electrical burns and impaired consciousness are more
      likely to undergo amputation. Since these are highly incapacitating injuries, it
      is very important to implement preventive measures.

PMID- 22464752
TI  - Prussian blue caged in spongiform adsorbents using diatomite and carbon nanotubes
      for elimination of cesium.
AB  - We developed a spongiform adsorbent that contains Prussian blue, which showed a
      high capacity for eliminating cesium. An in situ synthesizing approach was used
      to synthesize Prussian blue inside diatomite cavities. Highly dispersed carbon
      nanotubes (CNTs) were used to form CNT networks that coated the diatomite to seal
      in the Prussian blue particles. These ternary (CNT/diatomite/Prussian-blue)
      composites were mixed with polyurethane (PU) prepolymers to produce a quaternary
      (PU/CNT/diatomite/Prussian-blue), spongiform adsorbent with an in situ foaming
      procedure. Prussian blue was permanently immobilized in the cell walls of the
      spongiform matrix and preferentially adsorbed cesium with a theoretical capacity
      of 167 mg/g cesium. Cesium was absorbed primarily by an ion-exchange mechanism,
      and the absorption was accomplished by self-uptake of radioactive water by the
      quaternary spongiform adsorbent.

PMID- 22464751
TI  - SNPs in PTGS2 and LTA predict pain and quality of life in long term lung cancer
      survivors.
AB  - PURPOSE: Lung cancer survivors report the lowest quality of life relative to
      other cancer survivors. Pain is one of the most devastating, persistent, and
      incapacitating symptoms for lung cancer survivors. Prevalence rates vary with 80
      100% of survivors experiencing cancer pain and healthcare costs are five times
      higher in cancer survivors with uncontrolled pain. Cancer pain often has a
      considerable impact on quality of life among cancer patients and cancer
      survivors. Therefore, early identification, and treatment is important. Although
      recent studies have suggested a relationship between single nucleotide
      polymorphisms (SNPs) in several cytokine and inflammation genes with cancer
      prognosis, associations with cancer pain are not clear. Therefore, the primary
      aim of this study was to identify SNPs related to pain in lung cancer survivors.
      PATIENTS AND METHODS: Participants were enrolled in the Mayo Clinic Lung Cancer
      Cohort upon diagnosis of their lung cancer. 1149 Caucasian lung cancer survivors
      (440 surviving <3 years; 354 surviving 3-5 years; and 355 surviving >5 years)
      completed study questionnaires and had blood DNA samples available. Ten SNPS from
      PTGS2 and LTA genes were selected based on the serum-based studies in the
      literature. Outcomes included pain, and quality of life as measured by the SF-8.
      RESULTS: Of the 10 SNPs evaluated in LTA and PTGS2 genes, 3 were associated with
      pain severity (rs5277; rs1799964), social function (rs5277) and mental health
      (rs5275). These results suggested both specificity and consistency of these
      inflammatory gene SNPs in predicting pain severity in lung cancer survivors.
      CONCLUSION: These results provide support for genetic predisposition to pain
      severity and may aid in identification of lung cancer survivors at high risk for
      morbidity and poor QOL.

PMID- 22464753
TI  - Impact of two particle measurement techniques on the determination of N95 class
      respirator filtration performance against ultrafine particles.
AB  - The purpose of this experimental study was to compare two different particle
      measurement devices; an Electrical Low Pressure Impactor (ELPI) and a Scanning
      Mobility Particle Sizer (SMPS), to measure the number concentration and the size
      distribution of NaCl salt aerosols to determine the collection efficiency of
      filtering respirators against poly disperse aerosols. Tests were performed on
      NIOSH approved N95 filtering face-piece respirators (FFR), sealed on a manikin
      head. Ultrafine particles found in the aerosols were also collected and observed
      by transmission electron microscopy (TEM). According to the results, there is a
      systematic difference for the particle size distribution measured by the SMPS and
      the ELPI. It is largely attributed to the difference in the measurement
      techniques. However, in spite of these discrepancies, reasonably similar trends
      were found for the number concentration with both measuring instruments. The
      particle penetration, calculated based on mobility and aerodynamic diameters,
      never exceeded 5% for any size range measured at constant flow rate of 85 L/min.
      Also, the most penetrating particle size (MPPS), with the lowest filtration
      efficiency, would occur at a similar ultrafine size range <100 nm. With the ELPI,
      the MPPS was at 70 nm aerodynamic diameter, whereas it occurred at 40 nm mobility
      diameter with the SMPS.

PMID- 22464754
TI  - Visible light photocatalytic activity enhancement and mechanism of AgBr/Ag3PO4
      hybrids for degradation of methyl orange.
AB  - Novel AgBr/Ag(3)PO(4) hybrids were synthesized via an in situ anion-exchange
      method and characterized by X-ray diffraction (XRD), field emission scanning
      electron microscopy (FE-SEM), energy-dispersive spectroscopy (EDS) and UV-vis
      diffuse reflectance spectroscopy (DRS). Under visible light (lambda>420 nm),
      AgBr/Ag(3)PO(4) degraded methyl orange (MO) efficiently and displayed much higher
      photocatalytic activity than that of pure AgBr or Ag(3)PO(4). X-ray photoelectron
      spectroscopy (XPS) suggests that AgBr/Ag(3)PO(4) transformed to be
      Ag@AgBr/Ag(3)PO(4)@Ag system while remained good photocatalytic activity after 5
      times of cycle experiments. In addition, the quenching effects of different
      scavengers proved that reactive OH and h(+) played the major role for the MO
      degradation. The photocatalytic activity enhancement of AgBr/Ag(3)PO(4) is
      closely related to the efficient separation of electron-hole pairs derived from
      the matching band potentials between AgBr and Ag(3)PO(4), as well as the good
      electron trapping role of Ag nanoparticles in situ formed on the surfaces of AgBr
      and Ag(3)PO(4) particles during the photocatalytic reaction.

PMID- 22464755
TI  - Effective removal of sulfur from high-sulfur coal prior to use by dry
      chlorination at low temperature.
AB  - Desulfurization of high-sulfur coal prior to use by dry chlorination under
      various conditions was investigated. The contents of total carbon, total sulfur,
      pyritic sulfur, sulfate and organic sulfur of the coal were 72.48, 5.95, 1.08,
      0.66 and 4.22 wt.%, respectively. It was found that the chlorination temperature
      and particle size had a great influence on sulfur removal. The optimal
      chlorination temperature and particle size for sulfur removal was 350 degrees C
      and 48-75 MUm, respectively. Under optimal conditions, sulfur content in the
      chlorinated coal was 1.12 wt.%. The removal percentages of total sulfur, pyritic
      sulfur, sulfate and organic sulfur were 67.7, 93.0, 65.6 and 61.6, respectively,
      indicating that a high proportion of organic sulfur, pyritic sulfur and inorganic
      sulfur were removed by dry chlorination. Meanwhile, the fixed carbon did not lose
      appreciably. It was speculated that the removal of organic sulfur by dry
      chlorination at 350 degrees C proceeded mainly based on the equation
      2RS+Cl(2)=2RCl+S(2)Cl(2). The chlorinated coal thus obtained could be used in
      production of various carbon-containing materials such as metallurgical coke
      after a complete dechlorination pretreatment at 500-600 degrees C.

PMID- 22464756
TI  - Subclinical porcine circovirus type 2 infection does not modulate the immune
      response to an Aujeszky's disease virus vaccine.
AB  - Porcine circovirus type 2 (PCV2) negatively modulates the immune response in
      vitro. The objective of this study was to investigate if PCV2 interferes with the
      development of the immune response to Aujeszky's disease virus (ADV) vaccine,
      using an in vivo experimental subclinical model. Pigs were divided into four
      groups: (group CC) not infected with PCV2 and not vaccinated against ADV; (group
      IC) infected with PCV2 but not vaccinated against ADV; (group CV) not infected
      with PCV2 but vaccinated against ADV, and (group IV) infected with PCV2 and
      vaccinated against ADV. Pigs in groups IC and IV were inoculated intranasally
      with PCV2 and 14 days later, pigs in the CV and IV groups were vaccinated IM with
      a gE(-)tk(-) attenuated ADV vaccine. Clinical signs and weight gains were
      recorded from days 0 to 35 post-PCV2 inoculation (PI), at which point the pigs
      were euthanased and examined post-mortem. Throughout the experiment the PCV2 load
      was quantified in serum, antibodies to PCV2 and ADV were determined and antigen
      specific cellular responses against both viruses were measured using an
      interferon-gamma ELISPOT. PCV2 inoculated animals developed subclinical infection
      and had lower weight gain relative to non-infected controls. No differences were
      observed between the CV and IV groups in terms of the humoral or cellular immune
      responses to vaccination against Aujeszky's disease, suggesting that subclinical
      infection with PCV2 does not alter the response to this vaccine.

PMID- 22464757
TI  - Malignant change in a massive pleomorphic adenoma resembling the presentation of
      advanced inflammatory breast cancer.
AB  - Massive tumours of the parotid are uncommon as due to their site, they are
      usually removed at an earlier stage. We present a bizarre case of a carcinoma ex
      pleomorphic adenoma which mimicked an advanced breast cancer, complete with a
      'nipple-like' extension and peau d'orange changes in the overlying skin as a
      result of a dense dermal inflammatory response. A procedure akin to a mastectomy
      with facial nerve preservation was carried out for removal. To our knowledge,
      peau d'orange has not been reported before in parotid tumours.

PMID- 22464758
TI  - Surgical and prosthetic treatment for microphthalmia syndromes.
AB  - Our aim was to evaluate the long-term outcomes of prosthetic treatment and
      orbital expansion in the management of microphthalmia syndromes. We did a
      retrospective single-centre study of all cases of microphthalmia treated between
      1989 and 2010. The patients were divided into three groups: isolated
      microphthalmia, microphthalmia associated with micro-orbitism, and complex
      microphthalmia syndrome. To evaluate the results a score was computed for each
      patient by assessing the length of the palpebral fissure, the depth of the
      conjunctival fornix, and local complications together with an evaluation of the
      satisfaction of patients and their families. Forty-four children were included
      (27 boys and 17 girls). Twenty-seven had unilateral microphthalmia (61%) and 17
      bilateral microphthalmia (39%). Twelve patients were lost to follow up. The mean
      duration of follow-up was 12 years (range 4-21). Management involved an ocular
      conformer in only 31 patients (71%). The treatment was deemed satisfactory in all
      except 10 children. Surgical treatment with orbital expansion permitted good
      symmetry of the orbital cavities with a final mean difference of 9% (range 3-17)
      compared with the initial 16.8% (range 13.6-20.3). The prosthetic treatment gives
      satisfactory results. Despite limited indications and difficult follow-up, our
      experience emphasises the value of surgical treatment for severe micro-orbitism.

PMID- 22464759
TI  - Recurrent IVF failure: other factors.
AB  - IVF failure is a problem for a couple in the singular but can be a tragedy in the
      plural. Recurrent IVF failure has multiple known causes but many which are not
      routinely considered as part of the posttreatment analysis. The reason is there
      are several causes associated with lifestyle and other causes related to pre
      existing conditions that have only a tenuous or no apparent connection to
      fertility. This article examines the impact of obesity, cigarette smoke, uterine
      anatomy, body mass index, thyroid dysfunction, immune factors, the hereditary and
      acquired thrombophilias, and embryo transfer technique on recurrent IVF failure.

PMID- 22464760
TI  - Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with
      no pretreatment in GnRH antagonist protocol: a prospective randomized trial.
AB  - OBJECTIVE: To assess effects of estrogen pretreatment in GnRH antagonist
      protocol. DESIGN: Prospective, randomized multicenter study. SETTING: Ten private
      or university-based centers. PATIENT(S): A total of 472 patients undergoing
      IVF/ICSI. INTERVENTION(S): Randomization by sealed envelopes to receive 17beta
      estradiol (4 mg/d) or no pretreatment before daily recombinant FSH administration
      started on the first day of estrogen discontinuation or on cycle day 2 in
      nonpretreated women. MAIN OUTCOME MEASURE(S): The primary outcome measure was the
      number of retrieved oocytes. Secondary efficacy variables included total FSH
      dose, cycle duration, and outcome. RESULT(S): The mean numbers of retrieved
      oocytes (10.9 +/- 5.7 vs. 10.2 +/- 5.6) and obtained embryos (5.5 +/- 3.7 vs. 4.8
      +/- 3.7) were not significantly different between women allocated to estrogen
      pretreatment (n = 238) and no pretreatment (n = 234). Total FSH amount (1,557 +/-
      408 vs. 1,389 +/- 347 IU) and stimulation duration (10.8 +/- 1.4 vs. 10.0 +/- 1.5
      days) were slightly but significantly increased in pretreated patients. Positive
      pregnancy tests, ultrasound pregnancy rate, and delivery rate per cycle were
      similar (36%, 33%, and 26.6%, respectively, vs. 38.2%, 35.4%, and 30%).
      CONCLUSION(S): These data confirm that estrogen pretreatment is associated with
      requirement of higher FSH doses and longer duration of stimulation without any
      significant increase in the number of retrieved oocytes. However, estrogen does
      not affect cycle outcome and therefore might be used in clinical practice for
      programming IVF retrievals during working days. CLINICAL TRIALS REGISTRATION
      NUMBER: NCT01489852.

PMID- 22464762
TI  - Admissions for early parenting difficulties among women with infants conceived by
      assisted reproductive technologies: a prospective cohort study.
AB  - OBJECTIVE: To describe rate of and risks for residential early parenting service
      (REPS) admissions in women with infants conceived with assisted reproductive
      technology (ART). DESIGN: A prospective study of women who conceived with ART.
      Self-report telephone interview and questionnaire data were collected in two
      pregnancy and three postpartum waves. SETTING: Melbourne IVF and Royal Women's
      Hospital Reproductive Services, Victoria, Australia. PATIENT(S): A consecutive
      cohort of women with ART pregnancies. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): REPS admission up to 18 months postpartum. RESULT(S): Of 239 eligible
      women. 183 (77%) were recruited, six experienced pregnancy loss, and 153/177
      (86%) were retained. In total, 17% (26/153) of participants were admitted to a
      REPS, 3.37 times more than the population admission rate of 5.05%. Admission risk
      was increased by primiparity, inadequate breastfeeding advice, low caregiving
      confidence when discharged from maternity hospital, lower early postpartum mood,
      unsettled infant behavior, and insufficient help from others. CONCLUSION(S):
      Compared with spontaneous conception, women who conceived with ART are at
      elevated risk of early parenting difficulties. Early interventions to address
      breastfeeding difficulties, management of unsettled infant behavior, social
      isolation, and postpartum anxiety are indicated.

PMID- 22464761
TI  - Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine
      secretion, and promotes macrophage differentiation in an immunocompetent mouse
      model of endometriosis.
AB  - OBJECTIVE: To determine the effects of all-trans-retinoic acid (RA) on
      establishment and growth of endometrial lesions, peritoneal interleukin-6 (IL-6)
      and macrophage chemotactic factor-1 (MCP-1) concentrations, and CD38, CD11b, and
      F4/80 expression on peritoneal macrophages in an immunocompetent mouse model of
      endometriosis. DESIGN: Experimental transplantation study using mice. SETTING:
      Academic medical center. ANIMAL(S): C57BL/6 recipient mice and syngeneic green
      fluorescent protein transgenic (GFP+) mice. INTERVENTION(S): Recipient mice were
      inoculated with GFP+ minced uterine tissue to induce endometriosis and treated
      with RA (400 nmol/day) or vehicle for 17 days (3 days before to 14 days after
      tissue injection). MAIN OUTCOME MEASURE(S): Total number of GFP+ implants in
      recipient mice, number of implants showing visible blood vessels, total volume of
      established lesions per mouse, concentrations of IL-6 and MCP-1 in peritoneal
      fluid, and expression of CD11b, F4/80, and CD38 on peritoneal macrophages.
      RESULT(S): Retinoic acid treatment for 17 days reduced the number of implants
      versus controls and decreased the frequency of lesions with vessels. Peritoneal
      washings in RA-treated animals had lower concentrations of IL-6 and MCP-1 than
      controls 3 days after endometrial inoculation and lower levels of IL-6 on day 14
      after inoculation. Concomitant with these effects on day 14, CD38, CD11b, and
      F4/80 were higher on macrophages from RA-treated mice versus controls.
      CONCLUSION(S): The development of endometriotic implants is inhibited by RA. This
      effect may be caused, at least in part, by reduced IL-6 and MCP-1 production and
      enhanced differentiation of peritoneal macrophages.

PMID- 22464763
TI  - Decreased lactate and potassium levels in natural moisturizing factor from the
      stratum corneum of mild atopic dermatitis patients are involved with the reduced
      hydration state.
AB  - BACKGROUND: Atopic dermatitis (AD) shows dry skin. Water-soluble, low molecular
      weight components, collectively known as natural moisturizing factor (NMF), play
      an important role in maintaining the stratum corneum (SC) hydration. Previous
      studies focused on reduced levels of free amino acids (FAAs) in NMF from AD skin.
      It remains unknown, however, whether other NMF components are also altered in AD.
      OBJECTIVE: To characterize the levels of various NMF components in the SC of
      healthy subjects and in mild AD adult patients. METHODS: NMF components were
      extracted from three sequential tape-stripped SC samples obtained from the volar
      forearm. NMF components which were decreased in AD skin were topically applied to
      examine their contribution to SC moisturization in AD skin. RESULTS: We found
      that although FAAs levels were not remarkably reduced, levels of pyrrolidone
      carboxylic acid (PCA), lactate, urea, sodium and potassium were significantly
      decreased in NMF from mild AD skin. Among those components, only the topical
      application of potassium lactate effectively increased skin surface hydration
      indicating that reductions of lactate and potassium influence dry skin in mild AD
      patients. Unlike the distribution of filaggrin-derived FAAs and PCA, lactate,
      urea, potassium and sodium were abundant in the surface layer of the SC compared
      with the inner layer of the SC. Such findings strongly suggest that those
      components are supplied from outside the SC, i.e. they originate from sweat.
      CONCLUSION: The reduced levels of sweat-derived NMF components in mild AD
      patients suggests that impaired sweat function might in part result in the SC
      dryness.

PMID- 22464764
TI  - HOXA5 inhibits keratinocytes growth and epidermal formation in organotypic
      cultures in vitro and in vivo.
AB  - BACKGROUND: Homeobox transcription factors play important roles in epidermal
      renewal. Among them HOXA5 emerges as a promising member. However, its direct
      effect on epidermal biology, either to promote or to inhibit growth, is still
      controversial. OBJECTIVE: We proposed to unravel the role of HOXA5 in modulating
      keratinocytes growth and epidermal formation in organotypic cultures both in
      vitro and in vivo. METHODS: We transfected HaCaT cells with lentivirual vectors
      which over-expressed either wild-type or mutant HOXA5 cDNAs with deleted
      homeodomain. Subsequently we propagated the cells in organotypic cultures (OTCs)
      and then transplanted them into nude mice. Cell proliferation and cell cycle
      progression were detected. Epidermal morphogenesis and stratification were
      investigated by immunohistochemistry and immunofluorescence staining of a series
      of epidermal markers. RESULTS: HaCaT cells transfected with HOXA5 cDNAs displayed
      lower growth rate and delayed G1-S transition. HOXA5-transfected OTC exhibited an
      aberrantly organized epithelium with significantly increased TUNEL staining as
      well as decreased PCNA and K5 staining, while expression of differentiation
      markers as K10, involucrin and filaggrin were somewhat enhanced. However, under
      in vivo environment in nude mice which had great paracrine regulatory mechanisms,
      the aberrant phenotype was ameliorated as shown by a more regular tissue
      organization and normal expression of PCNA and K5. Inversely, cells transfected
      with the homeodomain-deleted protein exhibited accelerated growth and produced a
      more proliferative and better-orchestrated epidermis, as shown by well-expressed
      proliferation and differentiation markers. CONCLUSIONS: HOXA5 can suppress
      keratinocytes growth and epidermal formation. It probably activated antagonist
      genes against growth factors release, which depends on its homeodomain.

PMID- 22464765
TI  - Photodynamic therapy using a novel photosensitizer, TONS501, is similarly
      effective to ALA and EC036 photodynamic therapy on DMBA-and TPA-induced mouse
      skin papilloma.
AB  - BACKGROUND: Although topical photodynamic therapy (PDT) using 5-aminolevulinic
      acid (ALA) is applied for skin tumors including actinic keratosis, Bowen disease,
      and squamous cell carcinoma, there are no approved photosensitizers in
      dermatological field in Japan. TONS501 and TONS504 are novel hydrophobic
      photosensitizers with anionic and cationic chemical characteristics,
      respectively. OBJECTIVE: Using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12
      omicron-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin papilloma model,
      we compared the efficacy of ALA-, TONS501-, and TONS504-PDT on the skin tumor
      regression. METHODS: Following application of ALA, TONS501, TONS504 ointment or
      TONS501 lotion on DMBA- and TPA-induced mouse papillomas, 670 nm laser
      irradiation by LD670-05 diode laser was performed. Then tumor regression rate was
      calculated at the indicated time. RESULTS: The anti-tumor effect of ALA, TONS501,
      and TONS504 ointment was detected at 24 h and the maximal response was observed
      at 3 day following the PDT treatment. The maximal response was observed at 150
      J/cm(2) irradiation in all 3 photosensitizers. Although both ALA, TONS501
      (ointment)-PDT showed more potent anti-tumor effect compared with that of TONS504
      ointment or TONS501 lotion, no significant difference was detected between ALA
      ointment and TONS501 ointment. CONCLUSION: A novel TONS501ointment-PDT shows
      potent anti-tumor effect on DMBA- and TPA-induced mouse skin papilloma and might
      be more useful for the clinical applications.

PMID- 22464766
TI  - Epidermal alpha6beta4 integrin stimulates the influx of immunosuppressive cells
      during skin tumor promotion.
AB  - BACKGROUND: Induction of alpha6beta4 integrin in the differentiated epidermal
      cell layers in skin is a hallmark of human cutaneous squamous cell carcinoma
      (SCC) pathogenesis and stimulates chemically induced SCC formation in
      Invalpha6beta4 transgenic mice, which exhibit persistent expression of
      alpha6beta4 in the suprabasal epidermal layers. However, the molecular basis for
      the support of SCC development by suprabasal alpha6beta4 is not fully understood.
      OBJECTIVE: We examined the relevance for suprabasal alpha6beta4 expression in the
      epidermis for the recruitment of immunosuppressive leukocytes during the early
      stages of tumor promotion. METHODS: In this study, we made use of the
      Invalpha6beta4 transgenic mouse model, which exhibits expression of alpha6beta4
      integrin in the suprabasal layers of the epidermis driven by the involucrin
      promoter. First, we examined protein lysates from Invalpha6beta4 transgenic skin
      using a pro-inflammatory cytokine array panel. Next, we immunofluorescence
      labeling of murine skin sections was employed to immunophenotype tumor promoter
      treated Invalpha6beta4 transgenic skin. Finally, a macrophage colony stimulating
      factor (M-CSF) neutralizing antibody strategy was administered to resolve
      Invalpha6beta4 transgenic skin inflammation. RESULTS: Employing the
      Invalpha6beta4 transgenic mouse model, we show that suprabasal alpha6beta4
      integrin expression selectively alters the profile of secreted pro-inflammatory
      molecules by epidermal cells, in particular CXCL5 and M-CSF, in response to acute
      tumor promoter treatment. The induction of CXCL5 and M-CSF in Invalpha6beta4
      transgenic epidermis was shortly followed by an exacerbated influx of CD200R(+)
      myeloid-derived suppressor cells (MDSCs), which co-expressed the M-CSF receptor,
      and FoxP3(+) Treg cells compared to wild-type mice. As a result, the levels of
      activated CD4(+) T lymphocytes were dramatically diminished in Invalpha6beta4
      transgenic compared to wild-type skin, whereas similar levels of lymphocyte
      activation were observed in the peripheral blood. Finally, 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced CD200R(+) infiltrative cells and
      epidermal proliferation were suppressed in Invalpha6beta4 mice treated with M-CSF
      neutralizing antibodies. CONCLUSIONS: We conclude that aberrant expression of
      alpha6beta4 integrin in post-mitotic epidermal keratinocytes stimulates a pro
      tumorigenic skin microenvironment by augmenting the influx of immunosuppressive
      granular cells during tumor promotion.

PMID- 22464767
TI  - Update on aldosterone antagonists use in heart failure with reduced left
      ventricular ejection fraction. Heart Failure Society of America Guidelines
      Committee.
AB  - Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are
      guideline-recommended therapy for patients with moderate to severe heart failure
      (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in
      postmyocardial infarction patients with HF. The Eplerenone in Mild Patients
      Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated
      the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk
      of the primary endpoint of cardiovascular death or HF hospitalization (hazard
      ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause
      mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21
      months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York
      Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard
      therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should
      have another high-risk feature to be consistent with the EMPHASIS-HF population
      (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF
      hospitalization within 6 months or elevated B-type natriuretic peptide level).
      Renal function and serum potassium should be closely monitored. Dose selection
      should consider renal function, baseline potassium, and concomitant drug
      interactions. The efficacy of eplerenone in patients with mild HF symptoms
      translates into a unique opportunity to reduce morbidity and mortality earlier in
      the course of the disease.

PMID- 22464768
TI  - Effect of ivabradine vs atenolol on heart rate and effort tolerance in patients
      with mild to moderate mitral stenosis and normal sinus rhythm.
AB  - BACKGROUND: Patients with mitral stenosis become symptomatic at a higher heart
      rate. We studied the comparative efficacy of heart rate control with ivabradine
      or atenolol and its effect on effort tolerance in patients with mild-moderate
      mitral stenosis in normal sinus rhythm. METHODS AND RESULTS: Fifty patients with
      mild-moderate mitral stenosis in sinus rhythm were randomized to receive
      ivabradine or atenolol for 4 weeks each in an open-label, randomized, crossover
      design trial. A 24-hour Holter and treadmill test was performed at baseline and
      after each active treatment period. In the first treatment period, 23 patients
      were allocated to ivabradine (22 analyzed), and 27 were allocated to atenolol (26
      analyzed). In the second period, all 48 patients were analyzed. Ivabradine
      increased the mean total exercise time to 500.7 seconds (SD 99.7) from a baseline
      of 410.3 seconds (SD 115.4), and atenolol increased it to 463.7 seconds (SD
      113.1). The point estimate (absolute difference between ivabradine and atenolol)
      was 35.27 seconds (95% CI 15.24-55.20; P = .0009). The point estimate for
      decrease in the maximum exercise heart rate and mean heart rate were 7.64/min
      (95% CI 0.37-15.9; P = .04) and 5.61/min (95% CI 2.51-8.71; P = .0007),
      respectively. CONCLUSIONS: Ivabradine is more effective than atenolol for effort
      related symptoms in patients with mild-moderate mitral stenosis and normal sinus
      rhythm.

PMID- 22464769
TI  - Design and performance of a multisensor heart failure monitoring algorithm:
      results from the multisensor monitoring in congestive heart failure (MUSIC)
      study.
AB  - BACKGROUND: Remote monitoring of heart failure (HF) patients may help in the
      early detection of acute decompensation before the onset of symptoms, providing
      the opportunity for early intervention to reduce HF-related hospitalizations,
      improve outcomes, and lower costs. METHODS AND RESULTS: MUSIC is a multicenter
      nonrandomized study designed to develop and validate an algorithm for prediction
      of impending acute HF decompensation with the use of physiologic signals obtained
      from an external device adhered to the chest. A total of 543 HF patients (206
      development, 337 validation) with ejection fraction <=40% and a recent HF
      admission were enrolled. Patients were remotely monitored for 90 days using a
      multisensor device. Accounting for device failure and patient withdrawal, 314
      patients (114 development, 200 validation) were included in the analysis.
      Development patient data were used to develop a multiparameter HF detection
      algorithm. Algorithm performance in the development cohort had 65% sensitivity,
      90% specificity, and a false positive rate of 0.7 per patient-year for detection
      of HF events. In the validation cohort, algorithm performance met the
      prespecified end points with 63% sensitivity, 92% specificity, and a false
      positive rate of 0.9 per patient-year. The overall rate of significant adverse
      skin response was 0.4%. CONCLUSION: Using an external multisensor monitoring
      system, an HF decompensation prediction algorithm was developed that met the
      prespecified performance end point. Further studies are required to determine
      whether the use of this system will improve patient outcomes.

PMID- 22464770
TI  - Genetic testing for dilated cardiomyopathy in clinical practice.
AB  - BACKGROUND: Familial involvement is common in dilated cardiomyopathy (DCM) and
      >40 genes have been implicated in causing disease. However, the role of genetic
      testing in clinical practice is not well defined. We examined the experience of
      clinical genetic testing in a diverse DCM population to characterize the
      prevalence and predictors of gene mutations. METHODS AND RESULTS: We studied 264
      unrelated adult and pediatric DCM index patients referred to 1 reference lab for
      clinical genetic testing. Up to 10 genes were analyzed (MYH7, TNNT2, TNNI3, TPM1,
      MYBPC3, ACTC, LMNA, PLN, TAZ, and LDB3), and 70% of patients were tested for all
      genes. The mean age was 26.6 +/- 21.3 years, and 52% had a family history of DCM.
      Rigorous criteria were used to classify DNA variants as clinically relevant
      (mutations), variants of unknown clinical significance (VUS), or presumed benign.
      Mutations were found in 17.4% of patients, commonly involving MYH7, LMNA, or
      TNNT2 (78%). An additional 10.6% of patients had VUS. Genetic testing was rarely
      positive in older patients without a family history of DCM. Conversely in
      pediatric patients, family history did not increase the sensitivity of genetic
      testing. CONCLUSIONS: Using rigorous criteria for classifying DNA variants,
      mutations were identified in 17% of a diverse group of DCM index patients
      referred for clinical genetic testing. The low sensitivity of genetic testing in
      DCM reflects limitations in both current methodology and knowledge of DCM
      associated genes. However, if mutations are identified, genetic testing can help
      guide family management.

PMID- 22464771
TI  - ST2 has diagnostic and prognostic utility for all-cause mortality and heart
      failure in patients presenting to the emergency department with chest pain.
AB  - BACKGROUND: Elevated ST2 predicts future heart failure and/or death in patients
      with pulmonary diseases, heart failure, acute dyspnea, and acute coronary
      syndromes. This study assesses both diagnostic and prognostic utility of ST2 in
      patients with chest pain. METHODS AND RESULTS: From November 2007 to April 2010,
      995 patients attending the Emergency Department with chest pain were
      prospectively recruited. Troponin I (TnI), B-type natriuretic peptide (BNP),
      creatine kinase-myocardial band (CKMB), myoglobin, and ST2 were measured at 0 and
      2 hours. The diagnostic utility of ST2 for heart failure and prognostic utility
      for primary outcome of death and/or heart failure by 18 months was assessed.
      Elevated ST2 had sensitivity 73.5% (55.8%-86.4%) and specificity 79.6% (79.0%
      80.1%) for acute heart failure (n = 34) [compared with BNP sensitivity 88.2%
      (73.6%-95.3%), specificity 66.2% (65.7%-66.4%)]. Elevated ST2 conveyed risk of 18
      month primary outcome (n = 110), with an adjusted hazard ratio (HR) of 1.9 (1.2
      3.2), compared with BNP HR 2.8 (1.4-5.7), myoglobin HR 1.9 (1.1-3.3), TnI HR 1.7
      (1.0-2.7), and CKMB HR 0.9 (0.5-1.7). When ST2 and BNP were both elevated, risk
      was greater than if either marker was elevated in isolation (P < .001).
      CONCLUSIONS: ST2 was more specific for acute heart failure than BNP. ST2 is
      independently predictive of future death and/or heart failure and has incremental
      utility in combination with BNP.

PMID- 22464772
TI  - Defining the Role of ST2: A Multimarker Approach?

PMID- 22464773
TI  - Exercise oscillatory breathing and NT-proBNP levels in stable heart failure
      provide the strongest prediction of cardiac outcome when combining biomarkers
      with cardiopulmonary exercise testing.
AB  - BACKGROUND: N-Terminal pro-brain natriuretic peptide (NT-proBNP) and
      cardiopulmonary exercise testing (CPET)-derived variables are gold standards for
      assessing prognosis in heart failure (HF) patients. We sought to refine cardiac
      events prediction by performing a combined analysis of NT-proBNP with markers of
      exercise ventilatory efficiency. METHODS AND RESULTS: A total of 260 stable HF
      patients underwent measurements of plasma NT-proBNP levels before, at peak
      exercise, and at 1-minute CPET recovery phase along with peak oxygen uptake
      (VO(2)), ventilation to CO(2) production (VE/VCO(2)) slope, and exercise periodic
      breathing (EPB) determinations. After a median follow-up period of 20.6 months,
      there were 54 cardiac-related deaths. Univariate analysis including NT-proBNP at
      rest, at peak exercise, and at 1 minute recovery, peak VO(2), VE/VCO(2) slope,
      and EPB showed NT-proBNP to be the strongest independent predictor with
      equivalent performance for rest, peak, and recovery levels. Thus, only NT-proBNP
      at rest was considered (Harrel C 0.783, 95% confidence interval [CI] 0.722-0.844)
      with VE/VCO(2) slope (Harrel C 0.720, 95% CI 0.646-0.794), EPB (Harrel C 0.685,
      95% CI 0.619-0.751), and peak VO(2) (Harrel C 0.618, 95% CI 0.533-0.704). With
      bivariate stepwise analyses, NT-proBNP along with EPB emerged as the strongest
      prognosticators (Harrel C 0.800, 95% CI 0.737-0.862). CONCLUSIONS: In the
      refinement for robust outcome predictors in HF patients, NT-proBNP levels
      together with EPB led to the most powerful definition. VE/VCO(2) slope and peak
      VO(2) did not provide any prognostic adjunct. A biomarker/CPET approach seems
      very promising to warrant the continuous implementation in the prognostic work-up
      of HF patients.

PMID- 22464774
TI  - Percutaneous coronary sinus interventions to facilitate implantation of left
      ventricular lead: a case series and review of literature.
AB  - BACKGROUND: Valves, stenosis, and occlusion in the coronary sinus (CS) may affect
      the success of left ventricular (LV) lead implantation in cardiac
      resynchronization therapy (CRT). We present our experience in percutaneous CS
      intervention (PCSI) to facilitate LV lead implantation and stabilization. METHODS
      AND RESULTS: Transvenous LV lead implantation was attempted for CRT in a total of
      255 patients (mean age 61.0 +/- 12.5 y; 60 female, 160 ischemic etiologies) from
      January 2005 to November 2010. Seventeen patients (6.7%) needed PCSI. PCSI
      indications were stenosis in 10 patients, CS valve in 5 patients, chronic venous
      occlusion in 1 patient, and LV lead stabilization in 1 patient. CS angioplasty
      was performed in 16 patients (6.2%) and stenting in 3 patients (1.2%) to
      facilitate LV lead placement. Two patients needed both balloon angioplasty and
      stenting. LV leads were successfully inserted in 15/17 (88.2%) of the patients
      who needed PCSI. There were no complications related to PCSI. The overall success
      rate of LV lead implantation increased from 238/255 (93.3%) to 253/255 (99.2%)
      with the use of PCSI. CONCLUSIONS: PCSI is a useful and safe technique in
      transvenous LV lead placement in case of CS stenosis, valves, and lead
      instability.

PMID- 22464775
TI  - Low levels of vascular endothelial growth factor B predict left ventricular
      remodeling after acute myocardial infarction.
AB  - BACKGROUND: Left ventricular (LV) remodeling is a prognostically important
      development after acute myocardial infarction (AMI). We recently reported that
      vascular endothelial growth factor B (VEGFB) may be a potential new biomarker of
      LV remodeling. This potential biomarker was evaluated in the present study.
      METHODS AND RESULTS: Patients with AMI (n = 290) and healthy volunteers (n = 42)
      were included. Plasma VEGFB levels were assessed before discharge. LV remodeling
      was determined by echocardiography at 6 months' follow-up. Levels of VEGFB were
      elevated in AMI patients compared with healthy volunteers (1.5-fold; P = .001).
      Mean plasma levels of VEGFB were 64% higher (P < .001) in patients in whom LV end
      diastolic volume (EDV) decreased during follow-up (DeltaEDV <= 0; n = 144;
      reverse remodeling) compared with patients in whom DeltaEDV increased (DeltaEDV >
      0; n = 146; remodeling). Using logistic regression models, independent
      relationships were found between VEGFB (odds ratio [OR] 0.8, 95% confidence
      interval [CI] 0.7-0.9; P = .0007) and infarct territory (OR 1.7, 95% CI 1.1-2.8;
      P = .02). Patients with anterior MI and low levels of VEGFB had the highest risk
      of remodeling. VEFGB outperformed N-terminal pro-B-type natriuretic peptide to
      predict LV remodeling, and low levels of VEGFB (<100 pg/mL) provided a
      specificity of 90%. Adding VEGFB to a clinical model involving age, sex, smoking
      habit, and infarct territory resulted in a net reclassification index of 11.7%.
      CONCLUSIONS: Plasma levels of VEGFB increase after AMI and correlate with
      preservation of cardiac function. Low levels of VEGFB accurately predict LV
      remodeling. Therefore, circulating VEGFB may have clinical utility in the
      identification of patients at high risk of remodeling after AMI.

PMID- 22464776
TI  - Genetic tailoring of pharmacotherapy in heart failure: optimize the old, while we
      wait for something new.
AB  - BACKGROUND: The combination of angiotensin-converting enzyme (ACE) inhibitors and
      beta-adrenergic receptor blockers remains the essential component of heart
      failure (HF) pharmacotherapy. However, individual patient responses to these
      pharmacotherapies vary widely. The variability in response cannot be explained
      entirely by clinical characteristics, and genetic variation may play a role. The
      purpose of this review is to examine our current state of understanding of beta
      blocker and ACE inhibitor pharmacogenetics in HF. METHODS AND RESULTS: Beta
      blocker and ACE inhibitor pharmacogenetic studies performed in patients with HF
      were identified from the Pubmed database from 1966 to July 2011. Thirty beta
      blocker and 10 ACE inhibitor pharmacogenetic studies in patients with HF were
      identified. The ACE deletion variant was associated with greater survival benefit
      from ACE inhibitors and beta-blockers compared with the ACE insertion. Ser49 in
      the beta-1 adrenergic receptor, the insertion in the alpha-2C adrenergic
      receptor, and Gln41 in G-protein-coupled receptor kinase 5 are associated with
      greater survival benefit from beta-blockers, compared with Gly49, the deletion,
      and Leu41, respectively. However, many of these associations have not been
      validated. CONCLUSIONS: The HF pharmacogenetic literature is still in its very
      early stages, but there are promising candidate genetic variants that may
      identify which HF patients are most likely to benefit from beta-blockers and ACE
      inhibitors and patients that may require additional therapies.

PMID- 22464777
TI  - Responding to the financial abuse of people with dementia: a qualitative study of
      safeguarding experiences in England.
AB  - BACKGROUND: The risks of financial exploitation and abuse of people with dementia
      remain under-researched. Little is known of the views of those responsible for
      local adult safeguarding systems about prevention and redress. We explore current
      repertoires of responses of such persons and consider barriers and facilitators
      to minimizing risks of financial abuse for people with dementia. METHODS: Fifteen
      qualitative interviews were undertaken with a purposively sampled group of Adult
      Safeguarding Co-ordinators in England in 2011. Framework analysis delineated
      themes in the transcripts; these were included in an iteratively developed coding
      framework. RESULTS: Five themes were explored: (1) incidence of financial abuse;
      (2) impact of dementia on safeguarding responses; (3) warning signs of financial
      abuse, including neglect, unpaid bills, limited money for provisions; (4)
      encouraging preventive measures like direct debit to pay for bills, advance care
      plans, appointing Lasting Power of Attorney; and (5) barriers and facilitators in
      safeguarding, including the practice of financial agencies, cultural barriers,
      other systemic failures and facilitators. Not all systems of financial proxies
      are viewed as optimally effective but provisions of the Mental Capacity Act 2005
      were welcomed and seen as workable. CONCLUSIONS: Healthcare professionals may
      need to be more alert to the signs and risks of financial abuse in patients with
      dementia both at early and later stages. Engaging with safeguarding practitioners
      may facilitate prevention of abuse and effective response to those with
      substantial assets, but the monitoring of people with dementia needs to be
      sustained. In addition, professionals need to be alert to new risks from
      electronic crime. Researchers should consider including financial abuse in
      studies of elder abuse and neglect.

PMID- 22464778
TI  - [Influences of warming kidney prescription on antiviral therapeutic efficacy and
      creatine kinase in telbivudine-treated HBeAg-positive chronic hepatitis B
      patients].
AB  - To study the influences of warming kidney prescription on antiviral therapeutic
      efficacy and creatine kinase (CK) level in telbivudine-treated HBeAg-positive
      chronic hepatitis B patients with kidney yang deficiency syndrome. Ninety-six
      cases were enrolled and randomly divided into two groups (n=48 each): warming
      kidney prescription treatment or control. Both groups were treated for 52 weeks
      with telbivudine monotherapy, but the treatment group received additional
      treatment with the warming kidney prescription. Traditional Chinese medicine
      (TCM) syndrome score, biochemical response, virological response, serological
      response, CK level, and adverse reactions were recorded for each group in order
      to perform comparative analysis of the warming kidney prescription's effects. A
      total of 84 patients, including 43 cases in the treatment group, completed the
      study. The warming kidney prescription led to significantly improved total
      clinical syndrome efficacy, TCM syndrome score, biochemical response, virological
      response, and HBeAg serological responses, as evidenced by changes for each
      parameter observed in the treatment group versus the control group (respectively,
      88.37% vs. 63.41%, 4.97+/-1.88 vs. 10.13+/-3.72, 95.35% vs. 75.61%, 81.40% vs.
      56.10%, 48.84% vs. 26.83% (all, P less than 0.05)). No patient in either group
      experienced primary treatment failure. Seven cases, all from the control group,
      experienced virological breakthrough. Elevated CK was observed in both the
      treatment and control groups, but significantly more patients in the control
      group experienced this adverse reaction (respectively, 73.17% vs. 44.19%; P less
      than 0.01). The warming kidney prescription can increase telbivudine antiviral
      therapeutic efficacy and decrease the telbivudine-induced increase in creatine
      kinase in HbeAg-positive chronic hepatitis B patients with kidney yang deficiency
      syndrome.

PMID- 22464779
TI  - [Efficacy of lamivudine and adefovir de novo combination therapy or after mono
      therapy in chronic hepatitis B patients].
AB  - To investigate the efficacy of 104 weeks of lamivudine (LAM) and adefovir (ADV)
      de novo combination therapy, as compared to optimized combination therapy
      administered after 48 weeks of treatment with lamivudine or adefovir mono
      therapy, in chronic hepatitis B (CHB) patients. A total of 174 patients with CHB
      were equally divided among three treatment groups: LAM mono-therapy; ADV mono
      therapy; and LAM + ADV combination therapy. The patients in the LAM + ADV group
      were treated with LAM plus ADV for 104 consecutive weeks. The patients in the LAM
      or the ADV groups were first treated for 48 weeks with LAM or ADV, respectively,
      after which the patient's virological response was assessed. According to the
      results, the patient was continued on mono-therapy or switched to combination
      therapy for the subsequent 56 weeks. Virological and biochemical examinations
      were carried out at weeks 48 and 104. The rates of undetectable HBV DNA in the
      LAM mono-therapy, ADV mono-therapy, and LAM-ADV combination therapy groups at
      week 48 were 68%, 50%, and 84%, and at week 104 were 80%, 72%, and 95%,
      respectively. For the same groups, the virus breakthrough rates at week 48 were
      15%, 0%, and 0%, and at week 104 were 18%, 2%, and 0%, respectively. Statistical
      analysis showed significant differences for the rate of undetectable HBV DNA
      between LAM + ADV group and LAM group at week 48 (x2 = 4.473, P= 0.034) and at
      week 104 (x2 = 5.795, P = 0.016), LAM + ADV group and ADM group at week 48 (x2 =
      14.802, P less than 0.001) and week 104 (x2 = 5.547, P = 0.001). The hepatitis B
      e antigen (HBeAg) seroconversion rates at week 48 were 15% (x2 = 4.543, P =
      0.033), 13% (x2 = 4.035, P = 0.045) and 38%, and at week 104 were 21% (x2 =
      4.438, P = 0.035), 17% (x2 = 4.223, P = 0.04) and 44%, respectively, among
      patients positive for HBeAg. Statistical analysis showed that the differences
      among the three groups for each of these parameters were statistically
      significant (all, P less than 0.05). When compared with LAM or ADV mono-therapy
      followed by LAM+ADV at week 48, the LAM plus ADV de novo combination therapy for
      104 weeks provided CHB patients with better virological and serological responses
      and a lower drug resistance rate.

PMID- 22464780
TI  - [Construction and functional characterization of a monocistronic replicon based
      on the HCV genotype 2a promotor].
AB  - To construct a hepatitis C virus (HCV) genotype 2a monocistronic replicon and
      investigate its replication capabilities in the human hepatocarcinoma cell lines,
      Huh7.5 and Huh7.1, in order to determine its potential as a molecular tool for
      future in vitro studies of HCV replication and selection studies for putative
      anti-HCV drugs. Site-directed mutagenesis was used to delete the Core-E1-E2-p7
      NS2 fragment (about 3090 bp) from plasmid pJ6JFH1BlaRL. The resultant
      trianglepJ6JFH1BlaRL plasmid was digested with AgeI and AvrII to release the cDNA
      fragment (hereafter, referred to as fragment L) containing partial 5'
      untranslated region (UTR), the first 12 amino acid (aa) of HCV Core coding
      sequence, full-length coding sequences for the blasticidin-resistance gene,
      Renilla luciferase, foot-and-mouth disease virus (FMDV) 2a antiprotease and
      ubiquitin, and partial coding sequence for HCV NS3. To generate the monocistronic
      replicon, pSGRmJFH1BlaRL, fragment L was ligated into the pSGR-JFH1 vector that
      had been digested with AgeI and AvrII to remove the partial 5'-UTR, the first 19
      aa of HCV Core coding sequence, the full-length coding sequence for the neomycin
      phosphotransferase II gene, the internal ribosomal entry site from
      encephalomyocarditis virus, and partial HCV NS3 coding sequence. A replication
      defective mutant replicon, pSGRmJFH1BlaRL/GND, was constructed by a similar
      procedure using the pSGR-JFH1/GND vector. Fragment L was confirmed in both
      constructs by sequencing. Replicon RNAs were prepared from XbaI-linearized
      plasmid DNA templates with Invitrogen's T7 MEGAscript kit, and were purified by
      DNase I treatment and LiCl precipitation. RNAs were quanti?ed by optical density,
      and the quality and concentration were con?rmed by agarose gel electrophoresis.
      Replicon RNAs were transfected into Huh7.5 and Huh7.1 cells using Invitrogen's
      DMRIE-C transfection reagent at a ratio of 5 mug of lipid to 1mug of RNA. Time
      course assay of Renilla luciferase activity indicated the replicon's replication
      function. The pSGRmJFH1BlaRL monocistronic replicon and pSGRmJFH1BlaRL/GND
      replication-defective mutant replicon were successfully constructed. The
      pSGRmJFH1BlaRL replicon was replication-proficient in Huh7.5 and Huh7.1 cells,
      with replication peaking at 72 hours post-transfection and decreasing after 96
      hours. No replication was detected at any time point post-transfection for the
      defective mutant replicon. A monocistronic replicon of HCV genotype 2a was
      constructed and shown to be replication-proficient in human hepatocarcinoma cell
      lines.

PMID- 22464781
TI  - [Serum sodium concentration profile for cirrhotic patients and its effect on the
      prognostic value of the MELD score].
AB  - To analyze the characteristics of serum sodium in decompensated cirrhosis and
      evaluate the prognostic ability of the model for end-stage liver disease (MELD)
      in Na-containing models. Patients diagnosed with decompensated cirrhosis at our
      hospital were enrolled for study between June 2005 and October 2010. Patients
      were classified among three groups, according to serum sodium concentration: less
      than 125 mmol/L, 125 to 135 mmol/L, and more than 135 mmol/L. Mortality rates
      among the three groups were compared by Kaplan-Meier survival analysis. In
      addition, the different serum sodium concentrations were analyzed for
      correlations between Child-Pugh score and complication incidence rates of portal
      hypertension. The area under the receiver operating characteristic (ROC) curve
      (AUC) was used to compare the predictive abilities of MELD, MELD-Na, and the
      integrated (i) MELD scores for 3-month, 6-month and 1-year mortalities. A total
      of 467 patients were analyzed, and 50.54% had hyponatremia ( less than 135
      mmol/L). Sodium concentration was correlated with mortality, and Kaplan-Meier
      survival analysis indicated that mortality was significantly higher in each
      subgroup with lower sodium concentration (all, P = 0.000). Likewise, sodium
      concentration decreased in conjunction with increased severity of decompensation,
      as classified by Child-Pugh scoring (sodium: A more than B more than C;
      mortality: A less than B less than C). With the exception of digestive tract
      bleeding, complication incidence rates of hepatic encephalopathy, ascites,
      spontaneous bacterial peritonitis, and hepatorenal syndrome increased when sodium
      concentration decreased. For predicting 3-month mortality, the AUC scores of MELD
      were not significantly different from the MELD-Na and iMELD scores (P more than
      0.05). For predicting 6-month and 1-year mortality, the AUC scores of MELD-Na and
      iMELD were significantly higher than those of MELD (P less than 0.05).
      Hyponatremia is correlated with mortality and complications in decompensated
      cirrhosis patients. Incorporation of Na into the MELD may enhance it's prognostic
      ability.

PMID- 22464782
TI  - [Peg-IFNa-2a/RBV antiviral efficacy in cirrhotic hepatitis C patients after
      splenectomy or partial splenic embolization].
AB  - To investigate the antiviral efficacy of combination therapy with pegylated
      interferon alpha (peg-IFNa)-2a and ribavirin (RBV) in hepatitis C patients with
      liver cirrhosis after splenectomy or partial splenic embolization. Forty-nine
      hepatitis C patients with liver cirrhosis who were unable to use antiviral
      therapy because of hypersplenism were recruited for study and treated with
      splenectomy or partial splenic embolization. Three months later, a regimen of
      antiviral combination therapy was initiated with peg-IFNa-2a (once-weekly
      subcutaneous injection: 135 MUg or 180 MUg) and RBV (daily oral: 800 to 1200 mg),
      and was maintained for 48 weeks. The patients were followed up at treatment weeks
      1, 2, 4, 6, 8, and 12. Thereafter, follow-up was conducted every four weeks. The
      patients were observed until 24 weeks after treatment discontinuation. Follow-up
      testing included liver function, blood chemistry, renal function, and HCV RNA
      level. Any adverse reactions were recorded. Liver cirrhosis patients complicated
      by hypersplenism can be treated effectively with peg-IFNa-2a/RBV combination
      antiviral therapy after splenectomy or partial splenic embolization. The
      antiviral-induced sustained viral response rates was 65.00% in
      cirrhotic/hypersplenic hepatitis C patients receiving splenectomy and 58.62% in
      those receiving partial splenic embolization. Hypersplenism patients with
      hepatitis C-related cirrhosis achieved a good antiviral therapeutic effect with
      peg-IFNa-2a/RBV combination therapy following splenectomy or partial splenic
      embolization. This sequence of treatment may help to decrease incidences of
      chronic hepatitis C-induced liver failure and liver cancer in these patients.

PMID- 22464783
TI  - [Dynamic change of lipid peroxidation-related protein expression and the
      intervention effects of Yiguanjian decoction in a rat model of CCl4-induced liver
      fibrosis].
AB  - To investigate the dynamic change of lipid peroxidation-related protein
      expression and the intervention effects of Yiguanjian (YGJ) Decoction on liver
      fibrosis induced by CCl4 in rat. Fifty-seven male Wistar rats were randomly
      divided into a liver fibrosis group (n = 39) and a normal group (n = 18). The
      liver fibrosis was treated with peritoneal injection of 50% CCl4 for nine weeks.
      At the end of weeks 3 and 6 of CCl4 treatment, six rats were sacrificed to assess
      the status of liver fibrosis. At the end of week 7, the remaining -fibrotic rats
      were randomly divided into an untreated model group (M, n=15) and a YGJ-treated
      group (n = 12). The YGJ group was administered daily, oral YGJ Decoction for
      three weeks, concomitant with continued CCl4 treatment. The M group and normal
      group received the same treatment oral regimen and volume of distilled water. At
      the end of week 8, four rats in group M were sacrificed to observed the fibrosis
      status. At the end of week 9, the fibrotic rats were sacrificed for sampling.
      Liver function, histological changes, contents of hydroxyproline (Hyp) and
      malondialdehyde (MDA), activity of super oxidase dismutase (SOD) and L
      glutathione (GSH), protein expression of heat shock protein (HSP)70, heme
      oxygenase (HO)-1, transferrin, peroxiredoxin (Prxd) 6 and liver fatty acid
      binding protein (L-FABP) were detected. Compared with normal group-, the MDA
      content was increased significantly in M group at week 6 (M: 4.23+/-0.45 nmol/mg
      vs. normal: 2.22+/-0.59 nmol/mg, F = 60.13, P less than 0.01) and week 9 (M:
      6.29+/-1.23 nmol/mg vs. normal: 2.22+/-0.59 nmol/mg, F = 66.99, P less than
      0.01), but the SOD activity was decreased significantly at the same time points
      [week 6: (M: 196.94+/-39.20 U/mg vs. normal: 264.50+/-30.44 U/mg, F = 11.12, P
      less than 0.01]); [week 9: (M: 152.2+/-51.65 U/mg vs. normal: 264.50+/-30.44
      U/mg, F = 23.11, P less than 0.01)], as were the GSH content [week 6: (M: 48.47+/
      7.27 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 6.71, P less than 0.05]]; [week 9: (M:
      37.89+/-9.01 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 24.06, P less than 0.01]].
      Compared with group M at week 9, the YGH-treated model group had markedly
      decreased MDA (YGJ: 4.25+/-0.86 nmol/mg vs. M: 6.29+/-1.23 nmol/mg, F = 19.52, P
      less than 0.01], but significantly increased SOD (YGJ: 198.35+/-46.48 U/mg vs.
      152.21+/-51.65 U/mg, F = 4.65, P less than 0.05] and GSH (YGJ: 53.73+/-7.54
      nmol/mg vs. M: 37.89+/-9.01 nmol/mg, F = 19.23, P less than 0.01). Compared to
      normal rats at week 9, group M had significantly higher protein levels of HSP70
      (normal: 1.21+/-0.06 vs. M: 0.58+/-0.07, F = 166.87, P less than 0.01) and HO-1
      (normal: 1.11+/-0.06 vs. M: 0.58+/-0.06, F = 123.96, P less than 0.01), but
      significantly decreased levels of Prxd6 (normal: 0.04+/-0.05 vs. M: 1.49+/-0.05,
      F = 1215.85, P less than 0.01), transferrin (normal: 0.67+/-0.03 vs. M: 1.67+/
      0.04, F = 301.35, P less than 0.01), and L-FABP (normal: 0.24+/-0.02 vs. M:
      1.44+/-0.14, F = 219.05, P less than 0.01). Compared to group M at week 9, the
      YGJ treatment group showed significantly reduced HSP70 (YGJ: 0.82+/-0.04 vs. M:
      1.21+/-0.06, F = 92.31, P less than 0.01) and HO-1 (YGJ: 0.90+/-0.04 vs. 1.11+/
      0.06, F = 26.89, P less than 0.01), but significantly increased Prxd6 (YGJ:
      0.88+/-0.11 vs. 0.04+/-0.05, F = 150.17, P less than 0.01), transferrin (YGJ:
      1.36+/-0.13 vs. 0.24+/-0.02, F = 237.19, P less than 0.01), and L-FABP (YGJ:
      1.04+/-0.12 vs. 0.67+/-0.03, F = 27.53, P less than 0.01). YGJ treatment of
      fibrotic liver rats reduces lipid peroxidation damage by preventing generation of
      oxidizing substances.

PMID- 22464784
TI  - [Diagnostic efficacy of an ultrasound quantitative method in a rat model of
      experimental liver fibrosis].
AB  - To evaluate the efficacy of an ultrasound-based quantitative method to diagnose
      liver fibrosis using a rat model. Ultrasonography was performed on the livers of
      90 Sprague-Dawley rats with or without thioacetamide-induced fibrosis. The liver
      capsule thickness and 13 texture parameters of gray level co-occurrence matrix
      were extracted from the standard sonograms. After sacrifice, severity of liver
      fibrosis (S0-S4 classification) was diagnosed by histopathology. Analysis of
      variance and correlation statistical tests were used to analyze the differences
      between groups and determine the relationships between each of the 14
      quantitative ultrasound index points and the histological results, respectively.
      Discriminant analysis models were developed for quantitative diagnosis of liver
      fibrosis, and the leave-one-case-out method was used to verify the efficiency of
      models. All 14 indices were significantly correlated with the histological stages
      of fibrosis (P less than 0.05). The accuracy of the discriminant model for S0,
      S1, S2, S3 and S4 was 83.3%, 84.2%, 70.0%, 50.0% and 88.2%, respectively. In
      addition, 73.3% of cross-validated rats were accurately classified. Grouping S0
      as no fibrosis, S1 as mild fibrosis, S2 with S3 as moderate to severe fibrosis
      and S4 as early cirrhosis increased the accuracy of the discriminant model for
      these four groups (respectively, 91.7%, 84.2%, 69.0% and 88.2%) and allowed for
      78.9% of cross-validated rats to be correctly identified. Ultrasonography
      combined with texture analysis was a novel and accurate method to diagnose liver
      fibrosis in a rat model; further studies may provide insights into its
      applicability for quantitating liver fibrosis in other animal models or in
      clinic.

PMID- 22464785
TI  - [Sorafenib and octreotide combination therapy can inhibit proliferation of and
      induce apoptosis in human hepatoma cells].
AB  - To investigate the effects of sorafenib and octreotide combination treatment on
      cellular proliferation and explore the underlying molecular mechanisms by using
      an in vitro cell culture system with the human hepatoma cell line, HepG2. HepG2
      cells were treated with different concentrations of sorafenib and octreotide
      alone or in combination. Untreated HepG2 cells were used as controls. Treatment
      induced cytotoxicity was determined with the cell counting kit-8 by Sigma
      Aldrich, and rate of apoptosis was detected by flow cytometry. Fluorescent
      microscopy was used to observe rates of cell growth under the various treatments.
      Treatment-induced changes in protein expressions were detected by enzyme-linked
      immunosorbent assay (for vascular endothelial growth factor (VEGF)) and Western
      blotting (for the Mcl-1 apoptosis mediator and the ERK1/2 and PERK1/2 kinases).
      Sorafenib and octreotide, used alone or in combination, inhibited proliferation
      and induced apoptosis in HepG2 cells. Combination treatment was more effective
      than either mono-treatment (F = 200.398, P less than 0.05). Fluorescent
      microscopy showed that combination treatment stimulated phosphatidylserine, the
      marker of early apoptosis, better than either mono-treatment. VEGF expression in
      cultures exposed to combination treatment was also significantly lower than in
      mono-treatment or untreated control cultures (F = 1019.725, P less than 0.05).
      Western blotting showed that octreotide mono-treatment had no effect on Mcl-1
      expression (vs. control group; P more than 0.05) and that combination treatment
      significantly lowered Mcl-1 expression (vs. mono-treatment and control groups; P
      less than 0.05). None of the treatments affected ERK1/2 expression (all, P more
      than 0.05), while all treatments significantly lowered PERK1/2 expression (vs.
      control group; F = 2.401, P less than 0.05) and the combination treatment lowered
      PERK1/2 significantly more than either mono-treatment (P less than 0.05).
      Sorafenib and octreotide can inhibit proliferation and induce apoptosis in the
      human hepatoma cell line, HepG2. Combination treatment is significantly more
      efficacious (P less than 0.05) and produced synergistic effects. The mechanism
      underlying this phenomenon may depend on synergistic inhibition of VEGF, the 
      anti-apoptotic protein Mcl-1, and the proliferation-inducing PERK1/2.

PMID- 22464786
TI  - [Establishment of the Chang liver cell line stably overexpressing human UCP2 gene
      and its effect on mitochondrial membrane potential and reactive oxygen species].
AB  - To establish the Chang liver cell line stably overexpressing human uncoupling
      protein 2 (UCP2) and observe the effect of UCP2 on mitochondrial membrane
      potential (MMP) and reactive oxygen species (ROS). The Chang liver cell line was
      transfected with recombinant plasmid containing full-length human UCP2 cDNA
      (pcDNA3.1-hUCP2) or pcDNA3.1 empty vector. The stable cell line was established
      by antibiotic screening with Zeocin. UCP2 expression was detected by Western
      blotting and immunocytochemistry. The UCP2 overexpressing cells were pretreated
      with genipin at various doses (25, 50 and 100 munol/L). MMP and intracellular ROS
      were detected by fluorescence spectrophotometry. The total normalized protein
      content in UCP2 overexpressing cells was 1.6-fold higher than that in
      unmanipulated normal cells. The fluorescence intensities of Rhodamine123 and DCFH
      DA in UCP2 overexpressing Chang liver cells (11.11+/-2.76 and 4.97+/-0.62,
      respectively) were significantly lower than those in unmanipulated normal cells
      (15.56+/-2.55, P less than 0.01 and 6.14+/-1.25, P less than 0.05, respectively)
      and in cells transfected with empty vector (16.11+/-2.93, P less than 0.01 and
      6.23+/-1.13, P less than 0.05, respectively). Treatment of UCP2 overexpressing
      cells with 25, 50 and 100 munol/L genipin caused a dose-dependent increase in
      fluorescence intensities of Rhodamine123 (14.89+/-2.89, 17.89+/-2.93 and 24.00+/
      2.55, respectively, all P less than 0.01) and DCFH-DA (9.16+/-0.78, 10.84+/-1.09
      and 11.83+/-1.25, respectively, all P less than 0.01). The Chang liver cell line
      stably overexpressing UCP2 was established successfully. Using this cell system,
      UCP2 was found to play a role in mitochondrial function by regulating MMP and
      ROS.

PMID- 22464788
TI  - Patient-specific respiratory models using dynamic 3D MRI: preliminary volunteer
      results.
AB  - Organ and tumour motion has a significant impact on the planning and delivery of
      radiotherapy treatment. At present imaging modality such as four-dimensional
      computer tomography (4DCT) cannot be used to measure the variability of motion
      between different respiratory cycles. To create reliable motion models, one needs
      to acquire volumetric data sets of the lungs with sufficient sampling of the
      breathing cycle. In this paper we investigate the use of highly parallel MRI to
      acquire such data. A 32 channel coil in conjunction with a balanced SSFP sequence
      and a SENSE factor of 6 were used to acquire volumetric data sets in five healthy
      volunteers. The acquisition was repeated for seven series of different breathing
      patterns. The data acquired was of sufficient spatial resolution (5 * 5 * 5
      mm(3)) and image quality to carry out automated non-rigid registration. The
      acquisition rate (c.a. 2 volumes per second) allowed for a meaningful sampling of
      the different respiratory curves that were automatically obtained from the skin
      surface motion. This acquisition technique should provide images of high enough
      quality to create statistical respiratory models.

PMID- 22464789
TI  - Comparison between two absolute methods used for 177Lu activity measurements and
      its standardization.
AB  - A (177)Lu primary standard was developed at the ENEA-INMRI in the frame of an
      international comparison organized by BIPM and piloted by NIST (USA). The
      CIEMAT/NIST method with (3)H standard source as tracer was used for standardizing
      a solution of (177)Lu. The activity value was compared also with the measurements
      of the same mother solution carried out by the 4pigamma integral counting method.
      Particular efforts were made to identify and quantify the long-lived (177m)Lu
      impurity in the mother solution. The results obtained by the two methods are in
      good agreement within their standard uncertainties. The arithmetic mean of the
      two values is in good agreement with the Comparison Reference Value (CRV). By the
      new primary standard two well-type ionization chambers (ICs), one fixed and the
      other one portable, were calibrated with an uncertainty lower than 2%. These ICs
      are used for routinely applications in the activity measurements of short-lived
      radionuclides particularly useful for medical applications.

PMID- 22464790
TI  - Synthesis, characterization and biological evaluation of novel neutral fac
      M(CO)3(SNO) complexes (M=Re, 99mTc) bearing the o-methoxyphenylpiperazine moiety.
AB  - The synthesis, characterization and biological evaluation of two new neutral
      tricarbonyl fac-M(CO)(3)(SNO) (M=Re, (99m)Tc) bearing o-methoxyphenylpiperazine
      as pharmacophore and S-functionalized cysteine or penicillamine as chelators are
      reported. Competition binding tests showed good affinity for the 5-HT(1A)
      receptor (8 and 54 nM for 4a and 4b, respectively). Biodistribution studies in
      healthy animals showed high initial blood and liver uptake, fast blood and tissue
      depuration and negligible brain uptake.

PMID- 22464787
TI  - K(Ca)2 channels: novel therapeutic targets for treating alcohol withdrawal and
      escalation of alcohol consumption.
AB  - Small-conductance, calcium-activated potassium (K(Ca)2) channels influence
      neuronal firing properties, intrinsic excitability, and NMDA receptor-dependent
      synaptic responses and plasticity. In this mini-review, we discuss new evidence
      that chronic alcohol-associated plasticity critically involves K(Ca)2 channels in
      hippocampus, ventral tegmental area, and nucleus accumbens. K(Ca)2 channel
      activity can modulate the magnitude of excitation of midbrain dopamine neurons
      induced by acute alcohol exposure. Emerging evidence indicates that K(Ca)2
      channels regulate neuroadaptations to chronic alcohol that contribute to
      withdrawal hyperexcitability and escalation of voluntary alcohol consumption.
      Restoring K(Ca)2 channel activity can attenuate the severity of the alcohol
      withdrawal syndrome in vivo and withdrawal-associated neurotoxicity in vitro.
      Pharmacological modulation of K(Ca)2 channels can bi-directionally influence
      drinking behavior in rat and mouse models of voluntary alcohol consumption.
      Collectively, these studies using various rodent models have clearly indicated a
      central role for K(Ca)2 channels in the neuroplasticity of chronic alcohol
      exposure. In addition, accumulating evidence suggests that K(Ca)2 channels are a
      novel therapeutic target to alleviate the symptoms of alcohol withdrawal and
      reduce high amounts of alcohol drinking.

PMID- 22464791
TI  - Measurement of the 230U half-life.
AB  - The (230)U half-life was determined by measuring the decay curve of (230)U
      sources by various nuclear detection techniques: alpha-particle counting at a
      defined small solid angle; 4pialpha+beta counting with a windowless CsI sandwich
      spectrometer, a liquid scintillation counter and a pressurised proportional
      counter; gamma-ray spectrometry with a HPGe detector and nearly-2pi alpha
      particle counting with an ion-implanted silicon detector. Depending on the
      technique, the decay was followed for 100-200 d, which is 5-10 times the (230)U
      half-life. The measurement results of the various techniques were in good mutual
      agreement. The mean value, T(1/2)((230)U)=20.23 (2) d, is lower than the
      literature value which is based on one measurement in 1948 and resulted in a half
      life value of 20.8d without statement of uncertainty. A correction for the
      ingrowth of the long-lived (210)Pb and its daughter products may have been
      overlooked in the past.

PMID- 22464792
TI  - Development of synthetic environmental radioactivity reference materials.
AB  - In this paper, a novel way of developing synthetic environmental radioactivity
      reference materials via the sol-gel process is described. Two solid reference
      materials (both having a SiO(2) matrix) were synthesised by hydrolysing a liquid
      mixture of tetraethyl orthosilicate (TEOS), ethanol and standardised mixed
      radionuclide solutions. The certified values, which were in the Bqg(-1) range,
      for the radionuclides in the material were determined by NPL and compared with
      results from measurements made by 36 organisations from 17 countries using a
      'consensus' approach. The measurements were made within two wider test exercises
      (the NPL Environmental Radioactivity Proficiency Test Exercises 2009 and 2010).
      Certified activity concentration values were obtained for (60)Co, (133)Ba,
      (134)Cs, (137)Cs, (152)Eu, (154)Eu and (241)Am and indicative values were
      obtained for (55)Fe and (90)Sr.

PMID- 22464793
TI  - Feasibility study for the quantification of total protein content by multiple
      prompt gamma-ray analysis.
AB  - Protein is an important nutrient in foods. The classical nitrogen analysis method
      is the Kjeldahl technique, which is time-consuming and inconvenient. As a
      convenient method to quantify protein content in biological samples, the
      feasibility of application of multiple prompt gamma-ray analysis (MPGA) to the
      quantification was studied. Results for protein content are reported for several
      reference materials and prove the method to be reliable.

PMID- 22464794
TI  - Marine environmental quality and biodiversity.

PMID- 22464795
TI  - Mobile safe injecting facilities in Barcelona and Berlin.

PMID- 22464796
TI  - Action plan to regain unnecessary deferred blood donors due to malaria risk in
      Turkey.
AB  - Malaria was expected to be a major problem during blood donation in Turkey due to
      existence of malaria cases in southeastern region of Turkey. The present study
      aimed for the first time, to investigate malaria in "donors deferred for malaria
      risk" and to determine the regional rates of malaria deferral in Turkey. Blood
      samples were collected from several Blood Banks of southeastern provinces where
      local malaria cases still exist and from Blood Bank of Ege University Medical
      School (EUMS) located in western Turkey where malaria is eradicated decades ago.
      Plasmodium spp. and specific antibodies were investigated by stained smears,
      antigen detection, PCR and ELISA. Among the donors deferred for malaria risk,
      Plasmodium spp. were not detected by microscopy, PCR or antigen detection.
      Seroprevalances were 2% and 3.92% in western and southeastern regions,
      respectively. Rate of donor deferral for malaria risk was 0.9% in EUMS and
      deferrals were exclusively because of travel to southeastern Turkey. In
      southeastern provinces, deferrals were mainly due to malaria like fever history.
      The present study first time assessed regional rates of donor deferral due to
      malaria risk in Turkey. Previously, malaria was expected to be a major problem
      during blood donation in Turkey due to existence of malaria cases in southeastern
      region of Turkey. The results of the study showed that 97% of the deferrals were
      unnecessary. In conclusion, to reduce unnecessary donor deferrals in Turkey, in
      addition to comprehensive questioning for malaria history, the usage of a malaria
      antibody screening method should be initiated prior to deferral decision.

PMID- 22464797
TI  - Sonophotolytic diethyl phthalate (DEP) degradation with UVC or VUV irradiation.
AB  - This study investigated the degradation of diethyl phthalate (DEP) by sonolytic,
      photolytic and sonophotolytic processes. Two types of UV lamps, UVC (254 nm) and
      VUV (185 nm+254 nm), were combined with ultrasound (283 kHz). The pseudo-first
      order degradation rate constants were in the order of 10(-1)-10(-3) min(-1)
      depending on the processes. The sonolytic DEP degradation rate increased with
      increasing applied power. Photolytic or sonophotolytic degradation of DEP when
      using a VUV lamp appeared to be effective because the photo II (UVC/VUV) resulted
      in a significantly faster degradation than the photo I (UVC) processes due to the
      higher photon energy and higher hydroxyl radical generation by homolysis of water
      by VUV. Significant degradation and mineralization (TOC) of DEP were observed
      with the combined sonophotolytic processes. Moreover, synergistic effects of 1.68
      and 1.23 were exhibited at DEP degradation of the sonophoto I and sonophoto II
      processes, respectively. This was attributed to the UV-induced dissociation of
      hydrogen peroxide (H(2)O(2)) generated by the application of US to hydroxyl
      radicals. Therefore, US in sonophotolytic processes can play an important role in
      enhancing DEP degradation. Moreover, the sonophoto II process is more effective
      on the mineralization and biodegradability of DEP.

PMID- 22464798
TI  - [US-guided transhepatic drainage of a mediastinal abscess].
AB  - Anastomoses often leak after esophageal surgery; if they are not detected in
      time, leaks can give rise to complications like fluid collections,
      superinfections, and mediastinitis. Although these complications usually require
      surgical treatment, different series of patients successfully treated with
      conservative or minimally invasive approaches have been reported. We present the
      case of a patient who developed a mediastinal abscess after epiphrenic
      diverticulectomy. We treated the abscess with US-guided percutaneous transhepatic
      drainage to avoid surgical reintervention. Although other cases of a transhepatic
      approach to thoracic lesions have been reported, to our knowledge this is the
      first report of this technique in mediastinal abscesses. We recommend that
      transhepatic drainage be considered a therapeutic option in the management of
      these complications.

PMID- 22464799
TI  - Exofocal dopaminergic degeneration as antidepressant target in mouse model of
      poststroke depression.
AB  - BACKGROUND: Although poststroke depression (PSD) is a frequent chronic
      complication of stroke with high relevance for outcome and survival, underlying
      pathomechanisms remain inadequately understood. This may be because suitable
      animal models are largely lacking and existing models are poorly characterized.
      METHODS: Male 129/SV mice were subjected to 30-min middle cerebral artery
      occlusion (MCAo)/reperfusion and serial magnetic resonance imaging scans. A
      subset of animals received selective serotonin reuptake inhibitor citalopram
      starting 7 days after MCAo. Behavioral assessment was performed at 14 weeks. To
      identify biological correlates of PSD, we quantified corticosterone levels in
      serum and brain-derived neurotrophic factor levels in brain. The integrity of the
      mesolimbic dopaminergic system was assessed using tyrosine hydroxylase and
      dynorphin in situ hybridizations as well as dopamine transporter autoradiography.
      RESULTS: Left, but not right, MCAo, elicited anhedonia and increased anxiety and
      despair. This depression-like syndrome was associated with alterations in the
      mesolimbic reward system. MCAo resulted in delayed degeneration of dopaminergic
      neurons in ipsilateral midbrain, which was accompanied by reduced dopamine
      concentrations and decreased levels of dopamine transporter density along with
      increased brain-derived neurotrophic factor protein levels in ischemic striatum
      and increased dynorphin messenger RNA expression in nucleus accumbens. Chronic
      antidepressant treatment initiated as late as 7 days after stroke reversed the
      behavioral phenotype, prevented degeneration of dopaminergic midbrain neurons,
      and attenuated striatal atrophy at 4 months. CONCLUSIONS: Our results highlight
      the importance of the dopaminergic system for the development of PSD. Prevention
      of secondary neurodegeneration by antidepressants may provide a novel target for
      subacute stroke therapy.

PMID- 22464800
TI  - The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9
      leukemia stem cells.
AB  - Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific
      demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell
      (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain
      expression of the associated oncogenic program, thus preventing differentiation
      and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using
      tranylcypromine analogs active in the nanomolar range phenocopied Kdm1a knockdown
      in both murine and primary human AML cells exhibiting MLL translocations. By
      contrast, the clonogenic and repopulating potential of normal hematopoietic stem
      and progenitor cells was spared. Our data establish KDM1A as a key effector of
      the differentiation block in MLL leukemia, which may be selectively targeted to
      therapeutic effect.

PMID- 22464801
TI  - Association between dietary carbohydrate, glycemic index, glycemic load, and the
      prevalence of obesity in Korean men and women.
AB  - Intake of high-glycemic index (GI) food has been postulated to reduce satiety,
      resulting in an increased total energy intake and reduced access to body fat as
      fuel. Thus, we hypothesize that high dietary GI and glycemic load (GL) are
      associated with an increased prevalence of obesity in the Korean population.
      Dietary GI and GL were calculated for 933 Korean men and women based on dietary
      intake assessed by food frequency questionnaires and using a GI table developed
      from published GI databases in a cross-sectional design. Mean differences in
      dietary GL and carbohydrate intake between obese and nonobese men were
      statistically significant after adjusting for covariates (P = .027 and .021,
      respectively). High dietary GL and carbohydrate intake were negatively associated
      with the prevalence of obesity among men in a multivariate-adjusted logistic
      regression model (P for trend = .026 and .036, respectively). Statistically
      significant effects of dietary GI and GL on the prevalence of obesity among women
      were observed in a generalized linear model (P = .002 and .042, respectively) and
      a logistic regression model (P for trend < .001 and = .007, respectively), after
      adjusting for covariates. Women with higher dietary GI and GL were more likely to
      be obese, a result consistent with our hypothesis. However, an inverse
      association for dietary GL and carbohydrate and prevalence of obesity was found
      in men, suggesting that mechanisms contributing to the prevalence of obesity
      between sexes may be different.

PMID- 22464802
TI  - Plasma nitrate and nitrite are increased by a high-nitrate supplement but not by
      high-nitrate foods in older adults.
AB  - Little is known about the effect of dietary nitrate on the nitrate/nitrite/nitric
      oxide cycle in older adults. We examined the effect of a 3-day control diet vs
      high-nitrate diet, with and without a high-nitrate supplement (beetroot juice),
      on plasma nitrate and nitrite kinetics and blood pressure using a randomized 4
      period crossover controlled design. We hypothesized that the high-nitrate diet
      would show higher levels of plasma nitrate/nitrite and lower blood pressure
      compared with the control diet, which would be potentiated by the supplement.
      Participants were 8 normotensive older men and women (5 female, 3 male, 72.5 +/-
      4.7 years old) with no overt disease or medications that affect nitric oxide
      metabolism. Plasma nitrate and nitrite levels and blood pressure were measured
      before and hourly for 3 hours after each meal. The mean daily changes in plasma
      nitrate and nitrite were significantly different from baseline for both control
      diet + supplement (P < .001 and P = .017 for nitrate and nitrite, respectively)
      and high-nitrate diet + supplement (P = .001 and P = .002), but not for control
      diet (P = .713 and P = .741) or high-nitrate diet (P = .852 and P = .500). Blood
      pressure decreased from the morning baseline measure to the three 2-hour postmeal
      follow-up time points for all treatments, but there was no main effect for
      treatment. In healthy older adults, a high-nitrate supplement consumed at
      breakfast elevated plasma nitrate and nitrite levels throughout the day. This
      observation may have practical utility for the timing of intake of a nitrate
      supplement with physical activity for older adults with vascular dysfunction.

PMID- 22464803
TI  - Dietary protein intake is associated with favorable cardiometabolic risk factors
      in adults: Tehran Lipid and Glucose Study.
AB  - In this study, we investigated the hypothesis that dietary protein content and
      type are related to cardiometabolic risk factors including body mass index, waist
      circumference (WC), serum triglycerides, high-density lipoprotein cholesterol
      (HDL-C), serum fasting glucose, and blood pressure. This population-based study
      was conducted on 2537 subjects aged 19 to 70 years and selected from among
      participants of the Tehran Lipid and Glucose Study (2006-2008). Dietary data were
      collected using a validated semiquantitative food frequency questionnaire.
      Associations between intakes of total protein as well as the animal-to-plant
      (A/P) protein ratio and cardiometabolic risk factors were analyzed using
      multivariate linear regression models. Dietary protein intakes were 13.7% and
      13.6% of energy, in men and women, respectively; the A/P protein ratio in women
      was significantly higher than in men (1.8 +/- 1.4 vs 1.4 +/- 0.9). Body mass
      index was associated with total protein intake in men (beta = 0.14, P = .01) and
      A/P protein ratio in women (beta = 0.075, P = .01). Waist circumference was
      associated with total protein intake (beta = -0.048, P = .03) and A/P protein
      ratio (beta=0.031, P = .05) in women. Serum fasting glucose was associated with
      both total protein intake (beta=0.061 and 0.11, P < .05) and the A/P proteinratio
      (beta = -0.078 and -0.056, P < .05) in both men and women, respectively. Serum
      HDL-C was associated with total protein intake (beta = 0.107 and 0.07, P < .05)
      in both men and women, whereas diastolic blood pressure in women was associated
      with total protein intake (beta = -0.125, P = .01). In conclusion, higher dietary
      protein intake was associated with enhanced HDL-C levels, WC, and diastolic BP,
      and a higher ratio of A/P protein intake was related with lower serum fasting
      glucose andWC.

PMID- 22464804
TI  - Dairy foods are an important source of calcium and vitamin D among Canadian-born
      and Asian-born Chinese in Edmonton, Alberta.
AB  - Low intakes of calcium and vitamin D increase the risk for osteoporosis, bone
      fracture, and other health problems. This study aimed to examine the calcium and
      vitamin D intakes of Canadian-born Chinese (CBC) and Asian-born Chinese (ABC) in
      Edmonton, Canada, and to identify usual food sources of these nutrients. We
      hypothesized that CBC would have higher intakes of calcium and vitamin D than ABC
      and that the food sources of these nutrients would differ by region of birth
      (Canada vs Asia). Two in-person multipass 24-hour dietary recalls were
      administered for 1 weekday and weekend day for 81 healthy ethnically Chinese aged
      18 to 58 years. The risks for calcium and vitamin D inadequacy were calculated as
      were the contributions of specific foods to calcium and vitamin D intakes.
      Calcium intake was 781 +/- 337 mg/d for CBC and 809 +/- 369 mg/d for ABC (P =
      .737). Vitamin D intake was 3.8 +/- 3.4 MUg/d for CBC and 5.0 +/- 3.9 MUg/d for
      ABC (P = .158). Respective risks for calcium and vitamin D inadequacy were 36%
      and 98% for men and 78% and 100% for women. Dairy contributed most to the calcium
      (43%) and vitamin D (52%) intake of participants. For ABC, soybean products
      contributed to 8.1% of calcium, whereas fatty fish contributed to 16.7% of
      vitamin D. For CBC, red meats contributed to 11.1% of vitamin D. Dietary intakes
      of calcium and vitamin D need to be increased in Chinese Canadians through the
      promotion of dairy and culturally relevant sources of these nutrients.

PMID- 22464805
TI  - Out-of-hand nut consumption is associated with improved nutrient intake and
      health risk markers in US children and adults: National Health and Nutrition
      Examination Survey 1999-2004.
AB  - The purpose of this study was to determine the association of out-of-hand nut
      (OOHN) consumption with nutrient intake, diet quality, and the prevalence of risk
      factors for cardiovascular disease and metabolic syndrome. Data from 24-hour
      recalls from individuals aged 2+ years (n = 24,385) participating in the 1999
      2004 National Health and Nutrition Examination Survey were used. The population
      was divided into children aged 2 to 11, 12 to 18, and adults 19+ years, and each
      group was dichotomized into OOHN consumers and nonconsumers. Out-of-hand nut
      consumers were defined as those individuals consuming 1/4 oz of nuts or more per
      d. Means, standard errors, and covariate-adjusted analyses of variance were
      determined using appropriate sample weights. Diet quality was determined using
      the Healthy Eating Index-2005. Significance was set at P < .05. The percent of
      OOHN consumers increased with age: 2.1% +/- 0.3%, 2.6% +/- 0.3%, 6.5% +/- 0.5%,
      and 9.6% +/- 0.5% those aged 2 to 11, 12 to 18, 19 to 50, and 51+ years,
      respectively. The 2 latter groups were combined into a single group of consumers
      aged 19+ years for subsequent analyses. Consumers of OOHN from all age groups had
      higher intakes of energy, monounsaturated and polyunsaturated fatty acids,
      dietary fiber, copper, and magnesium and lower intakes of carbohydrates,
      cholesterol, and sodium than did nonconsumers. Diet quality was higher in OOHN
      consumers of all age groups. In children aged 2 to 11 years, consumers had a
      higher prevalence of overweight/obesity. In those aged 12 to 18 years, weight and
      percent overweight were lower in consumers. Adult consumers had higher high
      density lipoprotein cholesterol, red blood cell folate, and serum folate levels
      and lower insulin, glycohemoglobin, and C-reactive protein levels than did
      nonconsumers. Adult consumers also had a 19% decreased risk of hypertension and a
      21% decreased risk of low high-density lipoprotein cholesterol levels. Data
      suggested that OOHN consumption was associated with improved nutrient intake,
      diet quality, and, in adults, a lower prevalence of 2 risk factors for metabolic
      syndrome. Consumption of OOHN, as part of a healthy diet, should be encouraged by
      health professionals.

PMID- 22464806
TI  - Vitamin D supplementation has no effect on insulin resistance assessment in women
      with polycystic ovary syndrome and vitamin D deficiency.
AB  - Insulin resistance is one of the most common features of polycystic ovary
      syndrome (PCOS). Some studies suggest that vitamin D deficiency may have a role
      in insulin resistance; thus, the aim of the current study was to determine the
      effect of vitamin D supplementation on insulin resistance in women with PCOS and
      a vitamin D deficiency. We hypothesized that vitamin D supplementation would
      lower the glucose level and insulin resistance in women with PCOS and a vitamin D
      deficiency. The current study was a randomized, placebo-controlled, double
      blinded trial with 50 women with PCOS and a vitamin D deficiency, 20 to 40 years
      old, assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D3
      or a placebo (1 every 20 days) for 2 months (vitamin D, n = 24; placebo, n = 26).
      The fasting blood glucose, insulin, 25-hydroxyvitamin D, and parathyroid hormone
      levels, as well as the homeostasis model assessment of insulin resistance and
      quantitative insulin sensitivity check index were measured at baseline and after
      treatment. In the vitamin D group, the serum level of 25-hydroxyvitamin D
      increased (6.9 +/- 2.8 to 23.4 +/- 6.1 ng/mL, P < .0001), and the parathyroid
      hormone level decreased (70.02 +/- 43.04 to 50.33 +/- 21.99 MU IU/mL, P = .02).
      There were no significant changes in the placebo group. There was a significant
      increase in insulin secretion in the vitamin D group (P = .01), but this was not
      significant compared with the placebo group. The fasting serum insulin and
      glucose levels and the insulin sensitivity and homeostasis model assessment of
      insulin resistance did not change significantly by the end of the study. We were
      not able to demonstrate the effect of vitamin D supplementation on insulin
      sensitivity and insulin resistance in women with PCOS and vitamin D deficiency.

PMID- 22464807
TI  - Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents
      intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis.
AB  - Dietary products are among the therapeutic approaches used to modify intestinal
      microflora and to promote protective effects during the intestinal inflammatory
      process. Because the banana plant is rich in resistant starch, which is used by
      colonic microbiota for the anaerobic production of the short-chain fatty acids
      that serve as a major fuel source for colonocytes: first, green dwarf banana
      flour produces protective effects on the intestinal inflammation acting as a
      prebiotic and, second, combination of this dietary supplementation with
      prednisolone presents synergistic effects. For this, we used the
      trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Our results revealed
      that the protective effect produced by a combination of 10% green dwarf banana
      flour with prednisolone was more pronounced than those promoted by a single
      administration of prednisolone or a diet containing 10% or 20% banana flour. This
      beneficial effect was associated with an improvement in the colonic oxidative
      status because the banana flour diet prevented the glutathione depletion and
      inhibited myeloperoxidase activity and lipid peroxidation. In addition, the
      intestinal anti-inflammatory activity was associated with an inhibition of
      alkaline phosphatase activity, a reduction in macroscopic and microscopic scores,
      and an extension of the lesions. In conclusion, the dietary use of the green
      dwarf banana flour constitutes an important dietary supplement and complementary
      medicine product to prevention and treatment of human inflammatory bowel disease.

PMID- 22464808
TI  - Onion peel extract increases hepatic low-density lipoprotein receptor and ATP
      binding cassette transporter A1 messenger RNA expressions in Sprague-Dawley rats
      fed a high-fat diet.
AB  - In the present study, we hypothesized that onion peel extract (OPE) alters
      hepatic gene expression to improve blood cholesterol profiles. To investigate the
      effect of OPE to test our hypothesis, Sprague-Dawley rats were fed ad libitum for
      8 weeks with the control, high-fat diet (HFD) or the high-fat diet with 0.2% OPE
      supplementations (HFD + OPE). Messenger RNA (mRNA) levels of genes in cholesterol
      metabolism and fatty acid metabolism were examined by semiquantitative reverse
      transcriptase polymerase chain reaction. The OPE in HFD reverted high fat-induced
      reduction in mRNA levels of sterol regulatory element-binding protein-2, low
      density lipoprotein receptor, and hydroxyl-3-methylglutaryl coenzyme reductase
      genes in the liver comparable with the levels of the control group. Onion peel
      extract slightly increased stearoyl-coA desaturase 1 (SCD-1) expression compared
      with high-fat feeding. However, sterol regulatory element-binding protein-1c and
      fatty acid synthase were not affected by high-fat or OPE feeding. Onion peel
      extract also enhanced expression of ATP-binding cassette transporter A1,
      peroxisome proliferator-activated receptor gamma2 and scavenger receptor class B
      type I genes when compared with high-fat feeding. However, OPE did not influence
      high fat-triggered changes in apolipoprotein A1 mRNA levels and liver X receptor
      alpha were not affected by either high-fat or OPE feeding. Our results suggest
      that OPE changes the expression of genes associated with cholesterol metabolism
      in favor of lowering blood low-density lipoprotein cholesterol and enhancing high
      density lipoprotein cholesterol through increasing mRNA abundance of low-density
      lipoprotein receptor and ATP-binding cassette transporter A1 genes.

PMID- 22464809
TI  - Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose
      gene expression involved in adipogenesis and inflammation.
AB  - Chitooligosaccharide (CO) has been reported to have potential antiobestic effects
      in a few studies, but the antiobesity properties of CO and its related mechanisms
      in models of dietary obesity remain unclear. We investigated the effect of CO on
      body weight gain, size of adipocytes, adipokines, and lipid profiles in high-fat
      (HF) diet-induced obese mice and on the gene expression in adipose tissue using a
      complementary DNA microarray approach to test the hypothesis that CO
      supplementation would alleviate HF diet-induced obesity by the alteration of
      adipose tissue-specific gene expression. Male C57BL/6N mice were fed a normal
      diet (control), HF diet, or CO-supplemented HF diet (1% or 3%) for 5 months.
      Compared with the HF diet mice, mice fed the 3% CO-supplemented diet gained 15%
      less weight but did not display any change in food and energy intake.
      Chitooligosaccharide supplementation markedly improved serum and hepatic lipid
      profiles. Histologic examination showed that epididymal adipocyte size was
      smaller in mice fed the HF + 3% CO. Microarray analysis showed that dietary CO
      supplementation modulated adipogenesis-related genes such as matrix
      metallopeptidases 3, 12, 13, and 14; tissue inhibitor of metalloproteinase 1; and
      cathepsin k in the adipose tissues. Twenty-five percent of the CO-responsive
      genes identified are involved in immune responses including the inflammatory
      response and cytokine production. These results suggest that CO supplementation
      may help ameliorate HF diet-induced weight gain and improve serum and liver lipid
      profile abnormalities, which are associated, at least in part, with altered
      adipose tissue gene expression involved in adipogenesis and inflammation.

PMID- 22464810
TI  - Improvement of serum antioxidant status in humans after the acute intake of apple
      juices.
AB  - It is hypothesized that apples of 2 Brazilian cultivars with different content of
      sugars and antioxidant compounds promote similar effects on the antioxidant
      status and lipid peroxidation in human serum after acute intake. Nine healthy
      women ingested 300 mL of Golden Delicious or Catarina apple juice (AJ) or water,
      and blood samples were collected before and 1 hour after intake. After intake of
      both AJ, a similar and significant increase in serum antioxidant capacity and
      ascorbic and uric acid levels and a significant decrease in serum lipid
      peroxidation was observed. The increase in serum antioxidant capacity after
      consumption of both AJ was correlated directly with the uric acid levels and
      inversely with serum lipid peroxidation. In summary, the acute intake of AJ of 2
      cultivars promoted a similar effect on the antioxidant status and lipid
      peroxidation in human blood serum.

PMID- 22464811
TI  - Prevalence and natural history of hepatitis B and C infections in a large
      population of IBD patients treated with anti-tumor necrosis factor-alpha agents.
AB  - BACKGROUND: The prevalence rates of hepatitis B virus (HBV) and hepatitis C virus
      (HCV) in patients with inflammatory bowel disease (IBD) have been reported to be
      higher than rates of infection among the general population. Although several
      cases of HBV infection reactivation in IBD patients treated with anti-TNF-alpha
      agents have been described, no evidence exists that anti-TNF-alpha therapy
      exacerbates the course of HCV. The aims of this study were to assess the
      prevalence of HBV and HCV and the rate of HBV vaccination in a population of IBD
      patients; and to investigate the long-term effects of anti-TNF-alpha therapy in
      the subgroup with HBV or HCV infections. METHODS: 301 patients were studied.
      Prior to the initiation of anti-TNF-alpha therapy, serum samples were tested for
      HBsAg and anti-HBc, anti-HBs and anti-HCV antibodies. During the follow-up, HBsAg
      and anti-HBc positive patients underwent periodic blood testing for viral
      markers, HBV-DNA and liver function; anti-HCV positive patients were assessed for
      liver function and HCV-RNA. RESULTS: One patient was HBsAg positive (0.3%), and
      22 (7.3%) tested positive for anti-HBc. Seventy-two patients (23.9%) had been
      vaccinated for HBV. Four patients tested positive for anti-HCV (1.3%). During
      anti-TNF-alpha therapy, none of the patients experienced HBV or HCV reactivation.
      CONCLUSIONS: HBV and HCV infection rates were similar to infection rates among
      the general population. Less than one quarter of the patients had been vaccinated
      against HBV. Anti-TNF-alpha agents appear to be safe for patients with HBV
      infection; more data are needed for patients with HCV infection.

PMID- 22464812
TI  - Oral squamous cell carcinoma in a Crohn's disease patient taking azathioprine:
      case report and review of the literature.
AB  - Thiopurines are widely used for remission maintenance and post-operative
      recurrence prevention in Crohn's disease. The increased risk of cancer in
      transplant recipients on azathioprine is well recognized and there are concerns
      that this may also be true for inflammatory bowel disease patients. We report a
      case of a 33-year-old Caucasian woman with Crohn's disease treated with
      azathioprine for 9 years who developed an ulcerated lesion at the right superior
      retromolar trigone. Biopsy specimen revealed a squamous cell carcinoma.

PMID- 22464813
TI  - Fully covered self-expandable metal stents in biliary strictures caused by
      chronic pancreatitis not responding to plastic stenting: a prospective study with
      2 years of follow-up.

PMID- 22464814
TI  - Does complement play a role in bone development and regeneration?
AB  - The skeletal and the immune system are not two independent systems, rather, there
      are multifaceted and complex interactions between the different cell types of
      both systems and there are several shared cytokines. As a part of the innate
      immunity, the complement system was found to be an important link between bone
      and immunity. Complement proteins appear to be involved in bone development and
      homeostasis, and specifically influence osteoblast and osteoclast activity. This
      review describes the complex mutual regulation of the two systems, and indicates
      some of the negative side effects as a result of inappropriate or excessive
      complement activation.

PMID- 22464815
TI  - Mesenchymal stem cells promote neutrophil activation by inducing IL-17 production
      in CD4+ CD45RO+ T cells.
AB  - Mesenchymal stem cells (MSCs) are multi-potent with numerous mesenchymal-lineage
      differentiation potential and immunomodulatory capabilities. However, the
      immunoregulatory properties of MSCs are not clearly defined. The objective of the
      present study was to elucidate the role(s) of MSCs in IL-17 production and the
      subsequent effect(s) on neutrophil activation. We have demonstrated that human
      bone marrow-derived MSCs (BM-MSCs) instruct anti-CD3/anti-CD28 antibody-activated
      CD4(+) CD45RO(+) memory T cells, but not other CD4(+) subsets or CD8(+) T cells,
      to produce IL-17 after cell-cell contact. After the addition of IL-17, neutrophil
      phagocytic activity was increased. This is the first report on the ability of BM
      MSCs to induce IL-17 production in memory CD4(+) T cells that, in turn, promotes
      enhanced phagocytic activity of neutrophils. These results suggest that MSCs
      regulate the functional activation of neutrophils via their role in modulating IL
      17 from CD4(+) CD45RO(+) memory T cells.

PMID- 22464817
TI  - Progressive hip rehabilitation: the effects of resistance band placement on
      gluteal activation during two common exercises.
AB  - BACKGROUND: A critical issue for constructing a progressive rehabilitation
      program is the knowledge of muscle activation levels across exercises and within
      exercise modifications. Many exercises are offered to enhance gluteal muscle
      activation during functional rehabilitation but little data exists to guide the
      progression of exercise intensity during rehabilitation. The objective of this
      paper was to examine the effects of altering resistance band placement during
      'Monster Walks' and 'Sumo Walks.' METHODS: Nine healthy male volunteers formed a
      convenience sample. Sixteen electromyography channels measured neural drive of
      selected muscles of the right hip and torso muscles. Three resistance band
      placements (around the knees, ankles and feet) during the two exercises were
      utilized to provide a progressive resistance to the gluteal muscles while
      repeated measures ANOVA with Bonferroni adjustment was used to assess differences
      in mean EMG. The presentation of exercises and band placement were randomized.
      FINDINGS: Examining muscle activation profiles in the three hip muscles of
      interest revealed the progressive nature of the neural drive when altering band
      placement. Tensor fascia latae (TFL) demonstrated a progressive activation moving
      the band from the knee to the distal band placement, but not between the ankle
      and foot placements. Gluteus medius demonstrated a progressive activation moving
      distally between band placements. Gluteus maximus was preferentially activated
      only during the foot placement. INTERPRETATION: The band placements offered a
      progressive increase in resistance for hip rehabilitation, specifically the
      gluteal muscles. The added benefit of placing the band around the forefoot was
      selective enhancement of the gluteal muscles versus TFL presumably by adding an
      external rotation effort to the hips. This information may assist those who
      address gluteal activation patterns for patients suffering hip and back
      conditions where gluteal activation has been affected.

PMID- 22464818
TI  - Molecularly-targeted and biological anti-cancer therapy.

PMID- 22464816
TI  - Effect of supplementation with different fat sources on the mechanisms involved
      in reproductive performance in lactating dairy cattle.
AB  - Supplementary fat positively influences reproductive performance in dairy cattle,
      although the mechanisms involved are not clearly defined. Our objective was to
      determine the effects of four different fat supplements on follicle development,
      plasma steroid hormone concentrations and prostaglandin (PG) synthesis in
      lactating dairy cattle. Forty-eight early lactation Holstein-Friesian cows (21
      primiparous, 27 multiparous) were used in a completely randomized block design.
      Cows were fed the same basal TMR diet and received one of four fat supplements:
      (i) palmitic acid (18:0 fatty acid; Control), (ii) flaxseed (rich in 18:3 n-3
      fatty acid; Flax), (iii) conjugated linoleic acid (a mixture of cis-9, trans-11
      and trans-10, cis-12 isomers; CLA), and (iv) fish oil (rich in 20:5 and 22:6 n-3
      fatty acids; FO). All lipid supplements were formulated to be isolipidic;
      palmitic acid was added as necessary to provide a total lipid supplement intake
      of 500 g/day. Cows were synchronized to be in estrus on Day 15 of dietary
      treatment. All antral follicles were counted, and dominant follicles, subordinate
      follicles and corpora lutea were measured daily via transrectal ovarian
      ultrasonography for one complete estrous cycle. Blood samples were collected
      daily, and selected samples were analyzed for progesterone, estradiol, insulin
      like growth factor-1, insulin, cholesterol and non-esterified fatty acids. Estrus
      was synchronized a second time, and liver and endometrial biopsies were collected
      on Day 7 of the estrous cycle. Gene expression was evaluated for a number of
      genes involved in prostaglandin synthesis (endometrium) and fatty acid uptake and
      utilization (liver). Fat supplementation had little effect on follicle
      development. Cows receiving supplementary n-3 fatty acids had lesser plasma
      progesterone (P4) and smaller corpora lutea than cows receiving the CLA or
      Control supplements. Effects of fat supplementation on the endometrial expression
      of genes involved in PG synthesis were minor. Hepatic expression of SREBF1, ASCL1
      and FABP1 was reduced by FO supplementation. Reduced plasma P4 in n-3
      supplemented cows may lead to a suboptimal uterine environment for embryo
      development and hence reduced fertility compared to cows receiving the control or
      CLA supplements.

PMID- 22464819
TI  - Influence of chemical elements on mammalian spermatozoa.
AB  - Exposure to heavy metals is the most important risk factor in the assessment of
      spermatogenesis. About 30-40 % cases of infertility are caused by the male
      factor, and most of them are due to the small quantity of spermatozoa or to
      inferior spermatozoa quality. The negative impact on sperm motility, morphology
      and concentration of such chemical elements as Al, Cr, Cd, Pb or Fe was observed,
      while positive influence was noticed for Zn, Mg, and Ca. The influence of Mn, Cu,
      Ni or Se on spermatozoa is ambiguous. Chemical elements known as necessary for
      capacitation and acrosome reaction are Zn, Mg and Ca, while Cd and Pb disturb
      initiation and progress of the acrosome reaction. The positive effect of chemical
      elements Al, Cd, Cr, Cu, Ni, Pb, Se, and Zn, lies in their protection against
      oxidative stress. On the other hand, Al, Cu and Ni induce structural changes in
      the testes and epididymis or influence interactions with other chemical elements.

PMID- 22464820
TI  - TRAF2 docking with related proteins in silico studies.
AB  - Using the protein-protein docking program, this study investigates the
      relationship between TRAF2 and its related proteins and the diversity within the
      3D structures of TRAF2s. TRAF2 exists in monomer, trimer, and hexamer forms and
      it can combine with a number of proteins. Through comparative analysis we found
      that TRAF2(122), TRAF2(22), TRAF2(21740), TRAF2(2), TRAF2( 22ABC), and
      TRAF2(Phyre) perform very close homoousia in docking with the same group of
      ligands, though these TRAF2s come from different sources. The TRAF2-related
      proteins of cluster 1 change docking values strongly from top to bottom. The
      TRAF2- related proteins of clusters 2 and 3 have acceptable variation of the
      docking values. In consideration of the amino acid percentage, TRAF2-related
      proteins of cluster 2 represent appropriate docking values.

PMID- 22464821
TI  - Posttraumatic temporal TGF-beta mRNA expression in lens epithelial cells of
      paediatric patients.
AB  - The aim of the study was to determine temporal TGFB1, TGFB2 and TGFB3 gene
      expression profiles in the anterior lens capsule of paediatric patients with
      posttraumatic cataract. The patient group comprised 22 children selected with a
      fragment of anterior lens capsule obtained during elective cataract surgery and
      sampled for molecular analysis. The levels of TGF-beta isoforms in the anterior
      lens capsule were determined based on the number of mRNA copies per 1 MUg total
      RNA by real-time qRTPCR. Three time-related result clusters were identified based
      on hierarchical cluster analysis: 2.2, 4.4 and 15.0 months (time span from injury
      to anterior capsule sampling during surgery) and compared with regard to temporal
      gene expression profile and quantitative relations of TGF-beta1, 2 and 3 mRNAs.
      TGF-beta1, TGF-beta2, and TGF-beta3 mRNAs were detected in all anterior lens
      capsule samples. A comparative analysis revealed: TGF-beta1>TGF-beta2>TGF-beta3
      during the entire observation period. The TGF-beta mRNA levels continued to
      increase up to four months after injury, then returning close to the base levels
      after around 15 months. The expression patterns of TGF-beta isoforms showed a
      similar tendency. Differences in the expression levels of TGF-beta1 and TGF-beta2
      between the particular clusters were statistically significant. Posttraumatic
      transcriptional activities of TGF-beta1 and TGF-beta2 in the anterior lens
      capsule of paediatric patients depend on the time elapsing from injury. Our
      findings indicate that the transcriptional activities of TGFB family genes show a
      transient period of over-expression during the months after injury. TGF-beta1 is
      a dominant isoform expressed in lens epithelial cells following injury.

PMID- 22464822
TI  - Molecular characterization, polymorphism and association of porcine IBP4 gene.
AB  - The complete coding sequence of the porcine IBP4 gene was isolated using RT-PCR.
      Sequence analysis showed that the porcine IBP4 gene encodes a protein of 259
      amino acids which shares high homology with the insulin-like growth factor
      binding protein 4 (IBP4) of eight species: cattle (97 %), goat (97 %), chimpanzee
      (97 %), human (96 %), giant panda (96 %), sheep (95 %), Sumatran orangutan (95 %)
      and rabbit (93 %). This gene is structured in four exons and three introns as
      revealed by computer- assisted analysis. Phylogenetic analysis revealed that the
      porcine IBP4 gene has a close genetic relationship with the IBP4 gene of cattle.
      Polymorphism analysis indicated that there was an A/G substitution in the
      position of 134 bp of exon 2 and this mutation did not alter the encoded amino
      acids of the porcine IBP4 gene. PCR-Hha I-RFLP revealed that eight pig breeds
      displayed obvious genotype and allele frequency differences at this polymorphic
      locus. Association of this SNP with litter size traits was assessed in Large
      White (N = 100) and Landrace (N = 100) populations, and the results demonstrated
      that this polymorphic locus was significantly associated with the litter size of
      the first parity in Large White sows and Landrace sows (P <0.05). These data
      serve as a foundation for further insight into this novel porcine gene.

PMID- 22464823
TI  - Cytotoxic potential of vasoconstrictor experimental gingival retraction agents:
      in vitro study on primary human gingival fibroblasts.
AB  - The aim of this in vitro study was to evaluate the cytotoxic effects of the
      vasoconstrictor experimental gingival retraction agents (VEGRAs) in a dynamic
      setting. The strong cytotoxic effects of the astringent-based conventional
      gingival retraction agents (ACGRAs) on human gingival fibroblasts (HGFs) in vitro
      was our motivation to evaluate the biocompatibility of the vasoconstrictor-based
      experimental gingival retraction agents (VEGRAs) for the selected minimally
      invasive chemical agent. These agents were used to create three self-made
      retraction gels. Human gingival fibroblasts (HGFs) were treated with two groups
      of retraction agents: 1) three alpha- and beta-adrenergic agents (VEGRA-alphabeta
      s) based on 0.1%, 0.01% and 0.05% HCl-epinephrine, and 2) seven alpha-adrenergic
      agents (VEGRA-alpha-s), including two commercially available 0.05% HCl
      tetrahydrozoline solutions, one 0.05% HCl-oxymetazoline solution, 10% HCl
      phenylephrine solution, and three new self-made experimental 0.05% HCl-tetrahydro
      zoline-based gels. The methyl thiazolyl tetrazolium (MTT) colorimetric assay was
      performed to determine the oxidoreductive mitochondrial function after 3, 5, 10
      min and 24 h of incubation. The cytotoxic effect, measured by cell viability
      lower than the 50% threshold, was not observed at any time period, even 24 h
      after application of 0.05% HCl-tetrahydrozolinebased self-manufactured retraction
      gels. High cell viability values of human gingival fibroblasts after the
      treatment with the three self-made 0.05% HCl-tetrahydrozoline- based gels may
      serve as a basis for further studies aimed at selecting the best retraction
      agents biocompatible with gingival margin tissues.

PMID- 22464824
TI  - Electrochemical evaluation of extremely-low frequency magnetic field effects on
      sulphate-reducing bacteria.
AB  - The effects of 50 Hz magnetic fields on sulphate- reducing bacteria viability
      were studied electrochemically. Two types of graphite electrodes (pyrolytic and
      glassy carbon) covered with whole bacterial cells behind a dialysis membrane were
      used for electrochemical measurements. We found about 15% decrease of reduction
      peak current density (which indicates desulphurization activity of the bacterial
      cells - their metabolic activity) on cyclic voltammograms after magnetic field
      exposure compared to the control samples. We suppose that the magnetic field does
      not influence the metabolic activity (desulphurization) of sulphate-reducing
      bacteria but most probably causes bacterial death.

PMID- 22464825
TI  - Neural responses to emotional faces in women recovered from anorexia nervosa.
AB  - Impairments in emotional processing have been associated with anorexia nervosa.
      However, it is unknown whether neural and behavioural differences in the
      processing of emotional stimuli persist following recovery. The aim of this study
      was to investigate the neural processing of emotional faces in individuals
      recovered from anorexia nervosa compared with healthy controls. Thirty-two
      participants (16 recovered anorexia nervosa, 16 healthy controls) underwent a
      functional magnetic resonance imaging (fMRI) scan. Participants viewed fearful
      and happy emotional faces and indicated the gender of the face presented. Whole
      brain analysis revealed no significant differences between the groups to the
      contrasts of fear versus happy and vice versa. Region of interest analysis
      demonstrated no significant differences in the neural response to happy or
      fearful stimuli between the groups in the amygdala or fusiform gyrus. These
      results suggest that processing of emotional faces may not be aberrant after
      recovery from anorexia nervosa.

PMID- 22464826
TI  - Resting cerebral glucose metabolism and perfusion patterns in women with
      posttraumatic stress disorder related to sexual assault.
AB  - In the literature, numerous trials using neuroimaging techniques have
      investigated brain function in patients with post-traumatic stress disorder
      (PTSD). However, the contrasting results showed that improvements, including in
      the study design, were required to reach consistent and convincing conclusions.
      This study evaluated the functional neuroimaging pattern of resting cerebral
      blood flow and glucose metabolism in patients with PTSD related to sexual
      assault. Twelve patients were enrolled for both brain single photon emission
      computed tomography (SPECT) and (18)F-fluorodeoxyglucose positron emission
      tomography (PET) investigations. All data were analyzed with statistical
      parametric mapping 2 (SPM2). The PTSD patients showed significant relative
      decreases in perfusion in the left hippocampus and in the basal ganglia compared
      with the control group. The PTSD group also had significantly lower cerebral
      glucosemetabolic activity in the left hippocampus and the superior temporal and
      precentral gyri than in the control group. These specific patterns of perfusion
      and glucose metabolism may be closely related to various neurophysiologic
      symptoms of PTSD.

PMID- 22464827
TI  - Seizures and EEG patterns in Pallister-Killian syndrome: 13 new Italian patients.
AB  - BACKGROUND AND OBJECTIVES: Pallister-Killian syndrome (PKS) is a rare genetic
      disorder caused by a tissue-limited mosaic supernumerary isochromosome 12p.
      Typical facial dysmorphisms, pigmentary abnormalities, and some major
      malformations are frequently present. Neurological manifestations include mental
      retardation, hypotonia, and seizures. Epilepsy incidence ranged from 39 to 59% in
      a previously reported series. No specific clinical and EEG phenotype has ever
      been reported to describe seizure features, electroclinical patterns, and
      response to therapy in PKS. METHODS: This was a multicentre study conducted on 13
      Italian children with PKS, as diagnosed by clinical phenotype and confirmed in
      cultured fibroblasts. All patients underwent several polygraphic video-EEG
      recordings and brain magnetic resonance imaging. RESULTS AND CONCLUSIONS: All the
      patients presented with epilepsy and seizures that started at a mean age of 19
      months. In six cases, epilepsy started with epileptic spasms (ES) combined with
      focal seizures in another case. In four cases, seizures were focal, and this was
      followed by ES in two patients. In only two cases, epilepsy started with
      myoclonic seizures, and spasms were never observed. The study provides further
      evidence that epilepsy is a part of the phenotype of PKS, although a specific
      clinical and EEG pattern could not be identified. Our cases show how ES with late
      or first-year onset is the most common type of seizure. Despite a variable
      prognosis in terms of response to therapy, a significant proportion of patients
      achieved good seizure control.

PMID- 22464828
TI  - The making of a nutrition professional: the Association for Nutrition register.
AB  - OBJECTIVE: Nutritionists in the UK are at the start of an exciting time of
      professional development. The establishment of the Association for Nutrition in
      2010 has presented an opportunity to review, revitalize and expand the UK
      Voluntary Register of Nutritionists. In the UK and elsewhere, there is a need for
      a specialist register of nutritionists with title protection as a public
      safeguard. DESIGN: The new structure will base professional registration on
      demonstration of knowledge and application in five core competencies. Initially,
      there will be five specialist areas: animal; public health; nutritional
      scientist; food; sports and exercise. The wording and requirements linking the
      specialist areas to the competencies have been carefully defined by leading
      individuals currently on the existing register in these specialist areas. These
      have been evaluated by a random sample of existing registrants to check for
      accuracy of definitions and examples. Other work aims to establish a clear
      quality assurance framework in nutrition for workers in the health and social
      care sectors (UK Public Health Skills and Career Framework Levels 1-4) who
      contribute to nutrition activity, such as community food workers, nutrition
      assistants and pharmacists. Students, co-professional affiliates and senior
      fellows will also find a place in the new Association. The title 'nutritionist'
      is not currently legally protected in the UK and it is used freely to cover a
      range of unregulated practice. CONCLUSIONS: The establishment of a professional
      register to protect the public and to provide a clear identity for nutritionists
      is a vital step forward.

PMID- 22464829
TI  - Hyperparathyroid crisis: the timing of surgery.
AB  - BACKGROUND: Hyperparathyroid crisis is a rare, critical, and potentially fatal
      disease. The aim of this study was to classify different clinical courses of this
      disease, according to their preoperative medical responses and suggest the proper
      timing for surgery. METHODS: Patients who had undergone parathyroidectomies for
      hyperparathyroid crisis, were enrolled between January 1, 1994 and January 31,
      2009. Preoperative medical treatment and responses in terms of predisposing
      factors, preoperative localization, operative and pathological findings,
      postoperative outcome, and intervals from medicine to surgery, were
      retrospectively reviewed. RESULTS: A total of 11 patients, receiving more than 72
      hours of medical treatment, were divided into three types by preoperative medical
      responses. These included: Type I (three patients were resistant to medicine with
      persistent serum Ca > 14 mg/mL and were eventually treated with emergency
      surgery; two died of postoperative respiratory and hepatic failure), Type II (six
      patients with abnormal serum Ca < 14 mg/mL) and Type III (two patients in whom
      serum calcium returned to normal preoperatively. One patient was successfully
      treated with emergency surgery 18 hours post-hospitalization). We found no method
      for predicting the medical response, but all Type I patients exhibited high serum
      Ca >14 mg/mL after 48 hours of medical treatment. All abnormal parathyroid glands
      were >1.8 cm in length and easily detectable using preoperative ultrasonography.
      CONCLUSION: Because the response to pharmaceutical treatment of hyperparathyroid
      crisis is unpredictable, relieving the patient's dehydration is necessary first.
      Making a definite diagnosis and performing an early parathyroidectomy within 48
      hours are then required, especially in patients exhibiting poor medical response.

PMID- 22464830
TI  - Effects of clinoptilolite treatment on oxidative stress after partial hepatectomy
      in rats.
AB  - BACKGROUND/OBJECTIVE: Clinoptilolite is a natural zeolite crystal. Cytoprotective
      effects of clinoptilolite have been reported. However, so far there are no data
      about the effects of clinoptilolite treatment on oxidative stress after partial
      hepatectomy. In this experimental study, the effects of clinoptilolite treatment
      after partial hepatectomy on oxidative stress were evaluated. METHODS: There were
      four experimental groups (n=8): Group S, the sham group; Group H, the hepatectomy
      group; Group HC, the clinoptilolite treatment after partial hepatectomy group;
      and Group CS, the clinoptilolite-treated sham group. A 70% partial hepatectomy
      was performed for Group H and HC. Clinoptilolite (5mg/kg) was given to the rats
      orally (via gavage tube) twice a day for 10 days after hepatectomy.
      Malondialdehyde (MDA), Cu-Zn super oxide dismutase (SOD), and glutathione (GSH)
      levels were assessed to evaluate oxidative stress. RESULTS: Plasma and liver
      tissue MDA levels of Group HC were significantly lower than the H group (p=0.018
      and p=0.000, respectively). Liver tissue Cu-Zn SOD activity and GSH levels of
      Group HC were significantly higher than Group H (p=0.003, p=0.007, respectively).
      CONCLUSION: Clinoptilolite administration reduces oxidant activity and supports
      antioxidant response after partial hepatectomy.

PMID- 22464831
TI  - Diagnostic difficulties and treatment strategy of hepatic angiomyolipoma.
AB  - OBJECTIVE: Based on a large series of histopathologically confirmed hepatic
      angiomyolipomas, we retrospectively studied the typical diagnostic features of
      hepatic angiomyolipoma and proposed a treatment strategy for this disease.
      MATERIALS AND METHODS: From December 1997 to December 2007, 74 consecutive
      patients who received definitive treatment for hepatic angiomyolipoma, at a
      single tertiary center, were studied. RESULTS: There was a marked female
      predominance (54 females vs. 20 males) and the mean age was 42 years. Forty
      patients had no symptoms and the tumors were detected incidentally during a
      medical check-up. From this study, we proposed the typical diagnostic features of
      hepatic angiomyolipoma to be the absence of risk factors for malignancy, normal
      tumor marker levels, and typical imaging features on ultrasound (USG), abdominal
      contrast computed tomography (CT), or magnetic resonance imaging (MRI). Only 23%
      of patients could have been diagnosed before surgery using these features. One
      patient (1.4%) had a malignant angiomyolipoma, and died with distant metastases
      14 months after surgery. After a median follow-up of 64 months, there was no
      recurrence in the other 73 patients. CONCLUSION: Patients with typical diagnostic
      features suggestive of hepatic angiomyolipoma could be observed with regular
      surveillance. Definitive treatment should be performed when the tumor has
      symptoms/complications, when the tumor is enlarging, or when a malignant lesion
      cannot be ruled out.

PMID- 22464832
TI  - Waist circumference is an independent risk factor for prostatic hyperplasia in
      Taiwanese males.
AB  - PURPOSE: Benign prostatic hyperplasia is a common disease affecting older males.
      As obesity becomes an increasing problem worldwide, its role in prostatic
      hypertrophy has been discussed recently. The purpose of this study is to evaluate
      the relationship between waist circumferences and prostatic hyperplasia in
      Taiwan. METHODS: There were 539 men enrolled in the study who had health
      examinations at the Healthcare Center of Chang Gung Memorial Hospital; 53 were
      excluded because of history of conditions affecting prostatic volume. Their
      anthropometry was measured and serum prostate-specific antigen (PSA) levels as
      well as lipid profiles were analyzed. Prostate volume was measured by transrectal
      ultrasonography performed by experienced urologists. RESULTS: The mean prostate
      volume was 26.43 mL, whereas mean body mass index (BMI) was 25.27 kg/m(2) and
      mean waist circumference (WC) was 90.81 cm. By age-adjusted logistic regression,
      PSA > 4 ng/mL, WC >= 90 cm, and BMI > 24 kg/m(2) are associated with increased
      risk of developing prostatic hyperplasia; only WC >= 90 cm can be validated by
      multiple logistic regression. Further analysis of obesity patterns showed that
      abdominal overweight/obesity places patients at increased risk independently
      rather than high WC or high BMI alone. CONCLUSIONS: Study results showed that
      waist circumference >= 90 cm is an independent risk factor of prostatic
      hyperplasia in Taiwan. Men with abdominal overweight/obesity (WC >= 90 cm and BMI
      > 24 kg/m(2)) have a twofold risk of developing prostatic hyperplasia.

PMID- 22464833
TI  - Computed tomography indices and criteria for the prediction of esophageal
      variceal bleeding in survivors of biliary atresia awaiting liver transplantation.
AB  - BACKGROUND/OBJECTIVE: About 20% of biliary atresia (BA) survivors have attacks of
      esophageal variceal bleeding. We propose a method to evaluate the risk of
      esophageal variceal bleeding (EVB) using noninvasive indices by multislice
      computed tomography (CT). METHODS: We reviewed 31 potential living-related liver
      recipients aged 99-5314 days (mean, 1474 days) who underwent CT examinations
      using a 64-slice multislice CT scanner. Of the 31 patients, 19 patients (Group A)
      with fecal occult blood had EVB on esophagogastroduodenoscopy; the rest belonged
      to Group B. Splenic diameters (mm) were divided by body heights (m) and platelet
      counts (1000/mm(3)) to produce standardized ratios of transverse splenic
      length/body height/platelet count (SLHPR). The transverse diameters of
      paraesophageal veins (PVs) and perigastric veins (PGVs) were measured adjacent to
      the lower thoracic esophagus and within the lesser sac, respectively. RESULTS:
      According to a receiver operating characteristic curve analysis, the SLHPRs
      (r=0.833), transverse PV (r=0.957), and PGV (r=0.987) diameters were better
      predictors of EVB than demographic and laboratory variables. However, the
      transverse diameters of PGVs and PVs were the most accurate predictors of the
      EVB. CONCLUSION: For candidates awaiting liver transplantation, screening by
      noninvasive SLHPR and the transverse diameters of PGVs and PVs by CT may help to
      identify BA patients with a high risk of EVB.

PMID- 22464834
TI  - Doctor-patient communication, knowledge, and question prompt lists in reducing
      preoperative anxiety: a randomized control study.
AB  - OBJECTIVE: The aims of the study were to assess factors responsible for the
      reduction of preoperative anxiety in patients undergoing breast and abdominal
      surgeries. In particular, we investigated whether question prompt lists (QPL),
      patients' knowledge, or the communication skills of surgeons had effects on
      anxiety reduction. METHODS: Patients were randomly assigned to QPL and control
      groups. Anxiety was assessed on the State Trait Anxiety Inventory. RESULTS: Both
      groups showed significant reduction in anxiety between initial consultation and
      one day prior to surgery, with QPL patients showing a trend towards a greater
      reduction of anxiety after surgery and a significant reduction at the first
      outpatient follow-up. Satisfaction with consultation and the doctor's ability to
      answer questions concerning diagnosis, and treatment were significantly
      associated with anxiety reduction. CONCLUSION: Effective anxiety reduction hinged
      on doctors' communication abilities and patients' satisfaction with the
      consultation.

PMID- 22464835
TI  - Duodenal GIST metastasized to skull and orbit managed by surgery: a case report.
AB  - We report a 26-year-old man with 6 years, history of duodenal gastrointestinal
      stromal tumor (GIST) with liver, peritoneum and lung metastases. He presented
      with left eye ptosis, diplopia, left facial numbness and a left temporal fossa
      mass that was confirmed to be GIST with left skull and left orbit metastases.
      Craniectomy with cranioplasty, tumor excision and decompression were performed.
      There was an improvement of his visual symptoms and facial numbness. To our
      knowledge, this is one of the few reports of surgical management of GIST,
      metastasized to skull and orbit, with good symptomatic relief.

PMID- 22464836
TI  - Colonic volvulus detected by CT scan in a case with mental retardation and prune
      belly syndrome.
AB  - Colonic volvulus is a rare disease in children. Delayed diagnosis of the
      condition can often be fatal, especially in pediatric patients with mental
      retardation. We herein present the case of a female pediatric patient with
      colonic volvulus, prune belly syndrome, and mental retardation. Preoperative CT
      scans showed the characteristic signs of this disease. The volvulus occurred in
      the proximal colon of the colostomy. The release of the colonic volvulus and
      reconstruction of the colostomy were performed without the resection of the
      ischemic colon. The postoperative clinical course was uneventful.

PMID- 22464837
TI  - [Sedation and analgesia in emergency structure. Paediatry: Which sedation and
      analgesia for the child under spontaneous ventilation?].

PMID- 22464838
TI  - [Evaluation of the concordance between guidelines and transfusion practices in
      neonatal intensive care units].
AB  - OBJECTIVE: To assess the concordance rate between the prescriptions of blood
      products and Afssaps guidelines for transfusion practices in neonatology. STUDY
      DESIGN: Retrospective monocentric study. PATIENTS AND METHODS: Children
      transfused in the neonatology intensive care units in the Universitary Hospital
      of Rouen were included. Concordance rates between transfusion prescriptions,
      delivered and transfused products and the Afssaps guidelines were assessed. Any
      additional costs resulting from a theoretical discordance was also assessed.
      RESULTS: In 2006, 380 PSL were administered to 168 newborn children (NBC). Packed
      red blood cells (PRBC) represented the most often transfused products (n=290,
      76%). Fifty packed platelets (PP) were transfused (13% of the blood products) and
      41 fresh frozen plasmas (11%). Overall concordance rate between the Afssaps
      guidelines and the prescriptions was 64.9%. In 35.1% of cases, the prescription
      was excessive, compared to the recommendations. Excessive transfusion represented
      a total of 27,307 euros. CONCLUSION: Global concordance's rate between the
      guidelines and the prescriptions is fairly well. PRBC are the most blood product
      transfused. Excessive transfusions related to this concordance rate are leading
      to important theoretical costs. New informations to the guidelines are warranted
      to improve transfusional practices in this institution.

PMID- 22464839
TI  - [Major haemodynamic incident during continuous norepinephrine infusion: Beware of
      the infusion line. An avoidable postoperative hypertensive peak?].
AB  - The restoration of patients' mean arterial pressure after ineffective fluid
      resuscitation is obtained by vasopressive treatment such as norepinephrine.
      However, no guidelines exist concerning a norepinephrine infusion method: whether
      it be the norepinephrine concentration in the syringe, single or double pump
      administration via a carrier such as an isotonic saline solution, or use of
      minimized dead-volume extension sets. We present the case of a female patient
      requiring norepinephrine treatment, who quickly suffers a major haemodynamic
      incident (a sudden rise in systolic blood pressure above 220 mmHg associated with
      tachycardia up to 189 b/min). The main causes of this incident are discussed and
      infusion parameters considered with a view to developing an optimal infusion
      method for a drug with a specific therapeutic index.

PMID- 22464840
TI  - [Circumcision in children: an organizational or an ethical challenge?].
AB  - OBJECTIVES: To review society, ethical and anaesthesiological issues related to
      circumcision in children. STUDY DESIGN: Review. METHODS: Pubmed search and expert
      opinion RESULTS: Circumcision concerns 30 of male world population. Reasons are
      ritual, medical and hygienic. In Muslims, circumcision is usual performed before
      the age of six. Surgery is performed at best under sevoflurane general
      anaesthesia and a penile bloc. Level 1 and level 2 antalgics are used for 72
      hours, once the bloc has elapsed. In Jews, circumcision is performed soon after
      birth, in the community. Emla is the most convenient antalgics in this case.
      Except in case of emergency, circumcision under general anaesthesia should be
      delayed after 3 months as general anaesthesia is suspect to exert cerebral
      toxicity. Before the age of one year, there is a risk of increased respiratory
      problems following general anesthesia. Therefore, circumcision under general
      anaesthesia should be performed after one year of age. Circumcision may represent
      an adjunct to limit AIDS transmission in endemic countries. CONCLUSION: The
      ethical point associated with circumcision is to allow best analgesia, in a way
      matching child's age. Analgesia, is achievable by both the surgeon and the
      anesthesiologist.

PMID- 22464841
TI  - [Chylothorax: a rare complication of blunt chest trauma].

PMID- 22464842
TI  - Use of administrative data in pediatric research.

PMID- 22464843
TI  - So much to be learned about talking with children.

PMID- 22464844
TI  - Clinical lymph node staging--influence of slice thickness and reconstruction
      kernel on volumetry and RECIST measurements.
AB  - PURPOSE: Therapy response evaluation in oncological patient care requires
      reproducible and accurate image evaluation. Today, common standard in measurement
      of tumour growth or shrinkage is one-dimensional RECIST 1.1. A proposed
      alternative method for therapy monitoring is computer aided volumetric analysis.
      In lung metastases volumetry proved high reliability and accuracy in experimental
      studies. High reliability and accuracy of volumetry in lung metastases has been
      proven. However, other metastatic lesions such as enlarged lymph nodes are far
      more challenging. The aim of this study was to investigate the reproducibility of
      semi-automated volumetric analysis of lymph node metastases as a function of both
      slice thickness and reconstruction kernel. In addition, manual long axis
      diameters (LAD) as well as short axis diameters (SAD) were compared to automated
      RECIST measurements. MATERIALS AND METHODS: Multislice-CT of the chest, abdomen
      and pelvis of 15 patients with lymph node metastases of malignant melanoma were
      included. Raw data were reconstructed using different slice thicknesses (1-5 mm)
      and varying reconstruction kernels (B20f, B40f, B60f). Volume and RECIST
      measurements were performed for 85 lymph nodes between 10 and 60 mm using
      Oncology Prototype Software (Fraunhofer MEVIS, Siemens, Germany) and were
      compared to a defined reference volume and diameter by calculating absolute
      percentage errors (APE). Variability of the lymph node sizes was computed as
      relative measurement differences, precision of measurements was computed as
      relative measurement deviation. RESULTS: Mean absolute percentage error (APE) for
      volumetric analysis varied between 3.95% and 13.8% and increased significantly
      with slice thickness. Differences between reconstruction kernels were not
      significant, however, a trend towards middle soft tissue kernel could be
      observed.. Between automated and manual short axis diameter (SAD, RECIST 1.1) and
      long axis diameter (LAD, RECIST 1.0) no significant differences were found. The
      most unsatisfactory segmentation results occurred in higher slice thickness (3
      and 5 mm) and sharp tissue kernel. CONCLUSION: Volumetric analysis of lymph nodes
      works satisfying in a clinical setting. Thin slice reconstructions (<=3 mm) and a
      middle soft tissue reconstruction kernel are recommended. LAD and SAD did not
      show significant differences regarding APE. Automated RECIST measurement showed
      lower APE than manual measurement in trend.

PMID- 22464845
TI  - Chemotherapy in newborns and preterm babies.
AB  - The determination of appropriate dosing regimens for the treatment of infants and
      very young children with cancer represents a major challenge in paediatric
      oncology. Whereas dose reductions are commonplace for many chemotherapeutics in
      this patient group, the appropriateness of dose reductions for drugs is unclear
      when the limited number of published studies reporting on pharmacokinetics in
      infant patient populations are considered. Developmental physiological changes,
      potentially impacting significantly on drug disposition, occur throughout
      childhood, with a number of important changes observed within the first few weeks
      from birth. The current review focuses on the developmental physiology of preterm
      babies and infants and the potential impact of physiological changes on drug
      disposition, clinical response and toxicity. Dose reductions for a number of
      important anticancer drugs are compared between tumour types and clinical
      protocols. Where data exist, differences in pharmacokinetics between infants and
      older children are highlighted. In addition, the impact of confounding factors
      relating to the availability of appropriate drug formulations and ethical
      challenges concerning the conduct of clinical pharmacology studies in infant
      patient populations are addressed. As many currently used drugs are highly likely
      to be important in the treatment of cancer in infants and young children for the
      foreseeable future, it would seem advantageous for appropriately planned
      population pharmacokinetic studies to be carried out in this patient population.

PMID- 22464846
TI  - Paroxysmal kinesigenic dyskinesia: cortical or non-cortical origin.
AB  - Paroxysmal kinesigenic dyskinesia (PKD) is characterized by involuntary dystonia
      and/or chorea triggered by a sudden movement. Cases are usually familial with an
      autosomal dominant inheritance. Hypotheses regarding the pathogenesis of PKD
      focus on the controversy whether PKD has a cortical or non-cortical origin. A
      combined familial trait of PKD and benign familial infantile seizures has been
      reported as the infantile convulsions and paroxysmal choreoathetosis (ICCA)
      syndrome. Here, we report a family diagnosed with ICCA syndrome with an
      Arg217STOP mutation. The index patient showed interictal EEG focal changes
      compatible with paroxysmal dystonic movements of his contralateral leg. This
      might support cortical involvement in PKD.

PMID- 22464847
TI  - [123I]Epidepride neuroimaging of dopamine D2/D3 receptor in chronic MK-801
      induced rat schizophrenia model.
AB  - PURPOSE: [(123)I]Epidepride is a radio-tracer with very high affinity for
      dopamine D(2)/D(3) receptors in brain. The importance of alteration in dopamine
      D(2)/D(3) receptor binding condition has been wildly verified in schizophrenia.
      In the present study we set up a rat schizophrenia model by chronic injection of
      a non-competitive NMDA receptor antagonist, MK-801, to examine if
      [(123)I]epidepride could be used to evaluate the alterations of dopamine
      D(2)/D(3) receptor binding condition in specific brain regions. METHOD: Rats were
      given repeated injection of MK-801 (dissolved in saline, 0.3mg/kg) or saline for
      1month. Afterwards, total distance traveled (cm) and social interaction changes
      were recorded. Radiochemical purity of [(123)I]epidepride was analyzed by Radio
      Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [(123)I]epidepride
      neuroimages were obtained by ex vivo autoradiography and small animal SPECT/CT.
      Data obtained were then analyzed to determine the changes of specific binding
      ratio. RESULT: Chronic MK-801 treatment for a month caused significantly
      increased local motor activity and induced an inhibition of social interaction.
      As shown in [(123)I]epidepride ex vivo autoradiographs, MK-801 induced a decrease
      of specific binding ratio in the striatum (24.01%), hypothalamus (35.43%),
      midbrain (41.73%) and substantia nigra (37.93%). In addition, [(123)I]epidepride
      small animal SPECT/CT neuroimaging was performed in the striatum and midbrain.
      There were statistically significant decreases in specific binding ratio in both
      the striatum (P<.01) and midbrain (P<.05) between the saline and MK-801 group.
      CONCLUSION: These results suggest that [(123)I]epidepride is a useful radio
      tracer to reveal the alterations of dopamine D(2)/D(3) receptor binding in a rat
      schizophrenia model and is also helpful to evaluate therapeutic effects of
      schizophrenia in the future.

PMID- 22464848
TI  - Double conformational transition of alkali metal poly(L-glutamate)s in aqueous
      ethanol: counterion mixing effect revisited.
AB  - It was first found that alkali metal poly(L-glutamate)s show the coil-globule
      transition and the coil-helix transition sequentially in aqueous ethanol with
      increasing the solvent concentration. The counterion specificity for the former
      transition, i.e., Na(+)>K(+), Rb(+)>Li(+), Cs(+), proved to be somewhat different
      from that for the latter; Na(+)>Li(+)>K(+)>Rb(+)>Cs(+). Counterion mixing effects
      were also observed for both transitions; the most effective combinations to
      induce the transitions were Li(+)/Cs(+) and Li(+)/K(+), respectively. Solution
      viscometry, circular dichroism and alkali metal NMR line width measurements for
      the single-counterion systems revealed that the contact ion-pair formation hardly
      occurs for Li(+) even at the collapsed globule state and in the helix
      conformation. Unexpectedly, however, the specific binding of Li(+) was induced
      just by mixing with K(+) or Cs(+), when the helix content concomitantly
      increased. Mechanism for the counterion-specific "double transition" as well as
      the counterion mixing effect is discussed referring to the size-fitting model
      that has been proposed for the coil-globule transition of alkali metal
      poly(acrylate)s.

PMID- 22464849
TI  - Shedding light on protein-ligand binding by graph theory: the topological nature
      of allostery.
AB  - Allostery is a very important feature of proteins; we propose a mesoscopic
      approach to allosteric mechanisms elucidation, based on protein contact matrices.
      The application of graph theory methods to the characterization of the allosteric
      process and, more broadly, to obtain the conformational changes upon binding,
      reveals key features of the protein function. The proposed method highlights the
      leading role played by topological over geometrical changes in allosteric
      transitions. Topological invariants were able to discriminate between true
      allosteric motions and generic protein motions upon binding.

PMID- 22464850
TI  - Blocking the Na+/H+ exchanger 1 with cariporide (HOE642) reduces the hypoxia
      induced invasion of human tongue squamous cell carcinoma.
AB  - The Na+/H+ exchanger 1 (NHE1) plays a significant role in acidifying the tumour
      microenvironment, potentially contributing to the tumour's malignant potential.
      The mechanism by which NHE1 mediates cell invasion and migration, especially in
      human tongue squamous cell carcinoma (hTSCC), is unknown. In this study, the
      authors demonstrated that inhibition of NHE1 by cariporide (HOE642) suppressed
      the invasion and migration of Tca8113 cells under hypoxic conditions. Hypoxia
      also promoted the production of MMP-9, and the suppressive role of cariporide was
      enacted through the downregulation of MMP-9. The data demonstrated that NHE1
      plays a role in hTSCC invasion and that NHE1 might be a new target for hTSCC
      treatment.

PMID- 22464851
TI  - Evaluation of the correlation between disc displacements and degenerative bone
      changes of the temporomandibular joint by means of magnetic resonance images.
AB  - The aim was to evaluate the correlation between disc displacements and
      degenerative bone changes in magnetic resonance images (MRI) of 112 patients of
      both genders, with signs and symptoms of temporomandibular disorder. For this
      purpose, a calibrated examiner evaluated 224 MRI by assigning scores for the
      displacement of the disc and degenerative bone changes. Disc displacement was
      found in 58.42% of the temporomandibular joints (TMJs) evaluated. Anterior
      displacement of the disc with reduction was the most common, occurring in 67.18%
      cases of joints with disc displacement. Degenerative bone changes were observed
      in 53.94% of the TMJs analysed. There was significant correlation between disc
      displacement with reduction and condylar flattening, disc displacement without
      reduction and condylar flattening, disc displacement without reduction, and
      associated degenerative bone changes (flattening and erosion, flattening,
      osteophyte and erosion; flattening and osteophytes, erosion and sclerosis,
      flattening and sclerosis, flattening, osteophytes and sclerosis). The correlation
      between advanced cases of disc displacement and the occurrence of degenerative
      bone changes emphasises the importance of MRI for an accurate diagnosis and
      development of an appropriate treatment plan and in cases in which clinical
      examination is not sufficient for these purposes.

PMID- 22464853
TI  - Intra-articular loose osteochondroma of the temporomandibular joint.
AB  - Osteochondroma or osteocartilaginous exostosis is one of the most common benign
      bone tumours. It usually develops in the metaphyses of long flat bones, but
      rarely occurs in the oral and maxillofacial area, where it is generally
      associated with the coronoid process or the condyle. Loose osteochondromas inside
      the joint are generally a rare pathology usually described in large joints. The
      authors present a case of an intra-articular loose osteochondroma of the
      temporomandibular joint (TMJ), which represents the first case of such a
      pathological entity in the literature. The authors suggest that it should be
      considered in any differential diagnosis of loose bodies described in the TMJ.

PMID- 22464852
TI  - Association between the presence of a partially erupted mandibular third molar
      and the existence of caries in the distal of the second molars.
AB  - The objective of this study was to verify, using periapical radiographs, whether
      a partially erupted mandibular third molar is a factor in the presence of dental
      caries on the distal surface of the adjacent second molar. Two-forty six high
      quality periapical radiographs were selected, each showing a partially erupted
      mandibular third molar. The variables analyzed were: tooth number; gender; age;
      radiographic presence of caries on the distal surface of the adjacent molar; Pell
      and Gregory classification; Winter classification; angulation and distance
      between the second and mandibular third molar. The examiners were previously
      calibrated to collect data (kappa statistics from 0.87 to 1.0). The prevalence
      rate of caries on the distal surface of the second molar was 13.4%. In the
      logistical multivariate regression analysis, the angulation (OR=8.5; IC95%: 1.7
      43.8; p=0.011) and the gender (OR=3.3; IC95%: 1.4-7.7; p=0.005) remained
      statistically significant after an age adjustment was made. The results indicate
      that the presence of a partially erupted mandibular third molar with an
      angulation of 31 degrees or more, is a risk factor for caries on the distal
      surface of the mandibular second molars.

PMID- 22464854
TI  - The prevalence of TMJ osteoarthritis in asymptomatic patients with dentofacial
      deformities: a cone-beam CT study.
AB  - Osteoarthritis of the temporomandibular joint (TMJ) can be described as non
      inflammatory arthritic condition that results in degenerative changes of the
      joint structures. The aim of this study was to evaluate the skeletal morphology
      of the TMJ in patients with osteoarthritis with severe skeletal malocclusions
      (Class II and Class III) and patients with Class I occlusion as controls. Cone
      beam computed tomography images of 45 Class I, 28 Class II and 44 Class III
      joints of Caucasian patients were assessed for the presence of any degenerative
      changes in the condyle and fossa/eminence complex as described in the research
      diagnostic criteria for temporomandibular disorders (RDC/TMD). In all groups, the
      most commonly observed features were articular surface flattening and subcortical
      sclerosis. A combination of features that corresponds to a diagnosis of
      osteoarthritis was observed in 3% Class I, 43% Class II and 20% Class III patient
      joints. In conclusion, degenerative TMJ changes were more common in patients with
      skeletal jaw discrepancies, but wide inter-individual variations can be observed
      even in patients with clinically similar malocclusions.

PMID- 22464855
TI  - Evaluation of biotargeting and ecotoxicity of Co2+-containing nanoscale polymeric
      complex by applying multi-marker approach in bivalve mollusk Anodonta cygnea.
AB  - Cobalt (Co(2+)) is present in many nanoscaled materials created for various
      applications. The key goal of our study was to develop sensitive approaches for
      assessing the bio-risks associated with using novel Co(2+)-containing nanoscaled
      polymeric complex (Co-NC). Freshwater bivalve mollusk Anodonta cygnea (Unionidae)
      was subjected to 14 d action of the developed Co-NC, as well as of Co(2+) applied
      in the corresponding concentration (50 MUg L(-1)) or polymeric substance (PS).
      All experimental groups under study have demonstrated signs of toxic targeting,
      notably changes in DNA characteristics, oxidative stress (with particularities in
      each exposed group) and activation of anaerobiosis (Co(2+) and Co-NC). However,
      the group exposed to Co-NC showed some advantages that can be related to the
      activation of metallothionein (MT) function (increase in the level of MT-related
      SH-groups (MT-SH)): low level of oxyradical formation, no increase in protein
      carbonylation and vitellogenin-like proteins concentration unlike in Co(2+) and
      PS exposed groups. On the other hand, Co(2+) increased metal (Co, Cu, Zn and Cd)
      binding to MT (MT-Me) without changes in MT-SH level jointly with activation of
      oxyradical formation and apoptosis and decreasing of lysosomal membrane
      stability. PS per se initiated unbalanced changes in activities of the
      biotransformation enzymes ethoxyresorufin-O-deethylase and glutathione-S
      transferase. Thus, Co(2+) complexing with the developed PS prevented bio-toxic
      effects of free Co(2+) ions and PS per se, at least in the studied hydrobiont.
      The MT-SH was the main distinguishing index of Co-NC group selected by
      classification and regression tree analysis.

PMID- 22464856
TI  - Biochemical changes and GHG emissions during composting of lignocellulosic
      residues with different N-rich by-products.
AB  - Nitrogen availability plays a critical role in the biodegradation of organic
      matter during composting. Although the optimal initial C/N is known to be around
      25-30, the chemical form in which N is present influences microbial activity and
      therefore degradation rate and gaseous losses. This study was conducted to
      evaluate the influence of N availability on the composting of a mixture of
      lignocellulosic materials. Three composting piles were made of a mixture of wheat
      straw and cotton waste, each pile containing different N-rich animal by-products.
      The evolution of the main physico-chemical parameters was monitored (temperature,
      pH, electrical conductivity, C/N, NH(4)(+), NO(3)(-), water soluble C and N) as
      well as the enzymatic activity related to the cycle of the main nutrients (beta
      glucosidase, protease, alkaline phosphatase and fluorescein diacetate
      hydrolysis). Additionally, fluxes of CO(2), CH(4) and N(2)O emitted from the
      composting piles were measured by the closed-chamber technique. Cumulative CO(2)
      emissions were fitted to five different kinetic models with biological
      significance to C mineralization data. The application of the different N-rich
      residues had a significant effect on the C and N dynamics during composting.
      However, most enzymatic activities followed similar patterns in the three piles.
      The major CO(2) fluxes were recorded during the thermophilic phase, showing a
      direct relationship with temperature peaks. No CH(4) fluxes were detected for any
      of the composting piles during the whole trial, whereas low N(2)O emissions were
      found at the early beginning and during the maturation stage.

PMID- 22464857
TI  - Influence of oxalic acid formed on the degradation of phenol by Fenton reagent.
AB  - The objective of this work is to examine the influence of oxalic acid formed on
      the degradation of phenol by Fenton reagent. Oxalic acid formed at initial stage
      within 30 min significantly suppresses the reduction of ferric ion, thus
      terminating degradation reaction. The yield of oxalic acid is dependent on the
      amount of ferrous ion dosed since the minimal amount of oxalic acid is formed
      after the degradation reaction terminates. Mineralization of phenol by Fenton
      reagent stagnates after 120 min under the conditions used in this study. The
      reason why the mineralization stagnated can be assumed to be following two
      mechanisms other than the depletion of H(2)O(2). In the case where a small amount
      of ferrous ions is dosed, the reduction of ferric ions is minimal by oxalic acid
      formed. In the case where a large amount of ferrous ions is dosed, the amount of
      degradable organic compounds is insufficient owing to preferential conversion to
      oxalic acid. The mineralization can be enhanced by the intermittent dosing of
      ferrous ions, which facilitates the suppression of oxalic acid formation during
      the degradation by Fenton reagent.

PMID- 22464858
TI  - Bottom sediment as a source of organic contaminants in Lake Mead, Nevada, USA.
AB  - Treated wastewater effluent from Las Vegas, Nevada and surrounding communities'
      flow through Las Vegas Wash (LVW) into the Lake Mead National Recreational Area
      at Las Vegas Bay (LVB). Lake sediment is a likely sink for many hydrophobic
      synthetic organic compounds (SOCs); however, partitioning between the sediment
      and the overlying water could result in the sediment acting as a secondary
      contaminant source. Locating the chemical plumes may be important to
      understanding possible chemical stressors to aquatic organisms. Passive sampling
      devices (SPMDs and POCIS) were suspended in LVB at depths of 3.0, 4.7, and 6.7
      (lake bottom) meters in June of 2008 to determine the vertical distribution of
      SOCs in the water column. A custom sediment probe was used to also bury the
      samplers in the sediment at depths of 0-10, 10-20, and 20-30cm. The greatest
      number of detections in samplers buried in the sediment was at the 0-10cm depth.
      Concentrations of many hydrophobic SOCs were twice as high at the sediment-water
      interface than in the mid and upper water column. Many SOCs related to wastewater
      effluents, including fragrances, insect repellants, sun block agents, and
      phosphate flame retardants, were found at highest concentrations in the middle
      and upper water column. There was evidence to suggest that the water infiltrated
      into the sediment had a different chemical composition than the rest of the water
      column and could be a potential risk exposure to bottom-dwelling aquatic
      organisms.

PMID- 22464859
TI  - Application of positive matrix factorization in characterization of PM(10) and
      PM(2.5) emission sources at urban roadside.
AB  - The 24-h average coarse (PM(10)) and fine (PM(2.5)) fraction of airborne
      particulate matter (PM) samples were collected for winter, summer and monsoon
      seasons during November 2008-April 2009 at an busy roadside in Chennai city,
      India. Results showed that the 24-h average ambient PM(10) and PM(2.5)
      concentrations were significantly higher in winter and monsoon seasons than in
      summer season. The 24-h average PM(10) concentration of weekdays was
      significantly higher (12-30%) than weekends of winter and monsoon seasons. On
      weekends, the PM(2.5) concentration was found to slightly higher (4-15%) in
      monsoon and summer seasons. The chemical composition of PM(10) and PM(2.5) masses
      showed a high concentration in winter followed by monsoon and summer seasons. The
      U.S.EPA-PMF (positive matrix factorization) version 3 was applied to identify the
      source contribution of ambient PM(10) and PM(2.5) concentrations at the study
      area. Results indicated that marine aerosol (40.4% in PM(10) and 21.5% in
      PM(2.5)) and secondary PM (22.9% in PM(10) and 42.1% in PM(2.5)) were found to be
      the major source contributors at the study site followed by the motor vehicles
      (16% in PM(10) and 6% in PM(2.5)), biomass burning (0.7% in PM(10) and 14% in
      PM(2.5)), tire and brake wear (4.1% in PM(10) and 5.4% in PM(2.5)), soil (3.4% in
      PM(10) and 4.3% in PM(2.5)) and other sources (12.7% in PM(10) and 6.8% in
      PM(2.5)).

PMID- 22464860
TI  - Lactational transfer of mercury and polychlorinated biphenyls in polar bears.
AB  - We examined concentrations of total mercury (tHg, inorganic and methylated forms)
      and polychlorinated biphenyls (PCBs) in blood and milk from free-ranging Southern
      Beaufort-Chukchi Sea polar bears (Ursus maritimus) to assess maternal transfer of
      contaminants during lactation and the potential health risk to nursing young.
      Concentrations of contaminants in the blood of dependent and juvenile animals
      (ages 1-5 years) ranged from 35.9 to 52.2 MUg kg(-1) ww for tHg and 13.9 to 52.2
      MUg kg(-1) ww (3255.81-11067.79 MUg kg(-1) lw) for SigmaPCB(7)s, similar to those
      of adult females, but greater than adult males. Contaminant concentrations in
      milk ranged from 5.7 to 71.8 MUg tHg kg(-1)ww and 160 to 690 MUg SigmaPCB(11)s
      kg(-1) ww (547-5190 MUg kg(-1) lw). The daily intake levels for tHg by milk
      consumption estimated for dependent young were below the tolerable daily intake
      level (TDIL) of tHg established for adult humans. Although the daily intake
      levels of PCBs through milk consumption for cubs of the year exceeded the TDIL
      thresholds, calculated dioxin equivalents for PCBs in milk were below adverse
      physiological thresholds for aquatic mammals. Relatively high concentrations of
      non-dioxin like PCBs in polar bear milk and blood could impact endocrine function
      of Southern Beaufort-Chukchi Sea polar bears, but this is uncertain. Transfer of
      contaminants during mid to late lactation likely limits bioaccumulation of
      dietary contaminants in female polar bears during spring. As polar bears respond
      to changes in their arctic sea ice habitat, the adverse health impacts associated
      with nutritional stress may be exacerbated by tHg and PCBs exposure, especially
      in ecologically and toxicologically sensitive polar bear cohorts such as
      reproductive females and young.

PMID- 22464861
TI  - The behaviors and fate of polycyclic aromatic hydrocarbons (PAHs) in a coking
      wastewater treatment plant.
AB  - The occurrence, behaviors and fate of 18 PAHs were investigated in a coking
      wastewater treatment plant in Songshan coking plant, located in Shaoguan,
      Guangdong Province of China. It was found that the target compounds occurred
      widely in raw coking wastewater, treated effluent, sludge and gas samples. In raw
      coking wastewater, high molecular weight (MW) PAHs were the dominant compounds,
      while 3-6 ring PAHs predominated in the final effluent. The dominant compounds in
      gas samples were phenathrene, fluoranthene and pyrene, while they were
      fluoranthene, pyrene, chrysene and benzo[k]fluoranthene for sludge. The process
      achieved over 97% removal for all the PAHs, 47-92% of eliminations of these
      target compounds in liquid phase were achieved in biological stage. Different
      behaviors of PAHs were observed in the primary tank, anaerobic tank, aerobic
      tank, hydrolytic tank and coagulation tank units, while heavier and lower ones
      were mainly removed in anaerobic tank and aerobic tanks, respectively. Regarding
      the fate of PAHs, calculated fractions of mass losses for low MW PAHs due to
      transformation and adsorption to sludge accounted for 15-50% and 24-49%,
      respectively, while the rest was less than 1%. For high MW PAHs, the mass losses
      were mainly due to adsorption to sludge and separation with tar (contributing 56
      76% and 22-39%, respectively), and the removal through transformation was less.

PMID- 22464862
TI  - Identification of fungal proteases potentially suitable for environmentally
      friendly cleaning-in-place in the dairy industry.
AB  - Fourteen fungi were screened for ability to produce proteases with activity on
      milk protein. The proteases produced were assessed on a lab-scale in terms of
      their potential suitability for cleaning-in-place (CIP) in the dairy industry.
      Cleaning performance was assessed by determining the ability of the enzymes to
      remove an industrial-like milk fouling deposit from stainless steel. Based on the
      results observed, the extracellular protease activity produced by Schizophyllum
      commune was selected as most suitable for potential CIP application. A CIP
      procedure involving a sodium carbonate rinse followed by enzymatic cleaning with
      this fungal enzyme activity was developed. Satisfactory cleaning, judged by
      quantification of residual organic matter and protein on the stainless steel
      surface after cleaning, was achieved using the developed CIP procedure at 40
      degrees C. This CIP procedure, based on biodegradable enzymes working at low
      temperature is more environmentally favourable than conventional CIP methods
      using caustic based cleaning solutions at 70-80 degrees C. Potential
      environmental benefits of the developed enzymatic CIP procedure include reduced
      energy consumption, decreased chemical usage and a reduced requirement for pH
      neutralisation of the resultant waste prior to release.

PMID- 22464864
TI  - Comparison of intra-operative analgesia provided by intravenous regional
      anesthesia or brachial plexus block for pancarpal arthrodesis in dogs.
AB  - The aim of this study was to compare intravenous regional anesthesia (IVRA) and
      brachial plexus block (BPB) for intra-operative analgesia in dogs undergoing
      pancarpal arthrodesis (PA). Twenty dogs scheduled for PA were intramuscularly
      sedated with acepromazine (0.03 mg/kg), general anesthesia was intravenously (IV)
      induced with thiopental (10 mg/kg) and, after intubation, maintained with
      isoflurane in oxygen. In 10 dogs (GIVRA) IVRA was performed on the injured limb
      administering 0.6 ml/kg of 0.5% lidocaine. In 10 dogs (GBPB) the BPB was
      performed at the axillary level with the help of a nerve stimulator and 0.3 ml/kg
      of a 1:1 solution of 2% lidocaine and 1% ropivacaine was injected. During surgery
      fentanyl (0.002 mg/kg IV) was administered if there was a 15% increase of HR
      and/or MAP compared to the values before surgical stimulation. All the standard
      cardiovascular and respiratory parameters were continuously monitored during
      surgery. The duration of surgery and the time of extubation were recorded. Data
      were compared with a 1-way ANOVA test (P<0.05). No patients required fentanyl
      administration during surgery. All the recorded parameters were similar in the
      two groups. The two techniques were similar in providing intra-operative
      analgesia in dogs undergoing orthopaedic surgery.

PMID- 22464863
TI  - Assessing the chemical and biological accessibility of the herbicide isoproturon
      in soil amended with biochar.
AB  - There is considerable current interest in using biochar (BC) as a soil amendment
      to sequester carbon to mitigate climate change. However, the implications of
      adding BC to agricultural soil for the environmental fate of pesticides remain
      unclear. In particular, the effect of biochars on desorption behavior of
      compounds is poorly understood. This study examined the influence of BC on
      pesticide chemical and biological accessibility using the herbicide isoproturon
      (IPU). Soils amended with 1% and 2% BC showed enhanced sorption, slower
      desorption, and reduced biodegradation of IPU. Addition of 0.1% BC had no effect
      on sorption, desorption or biodegradation of IPU. However, the mineralization of
      (14)C-IPU was reduced by all BC concentrations, reducing by 13.6%, 40.1% and
      49.8% at BC concentrations of 0.1%, 1% and 2% respectively. Further, the ratio of
      the toxic metabolite 4-isopropyl-aniline to intact IPU was substantially reduced
      by higher BC concentrations. Hydroxypropyl-beta-cyclodextrin (HPCD) extractions
      were used to estimate the IPU bioaccessibility in the BC-amended soil.
      Significant correlations were found between HPCD-extracted (14)C-IPU and the IPU
      desorbed (%) (r(2)=0.8518, p<0.01), and also the (14)C-IPU mineralized (%)
      (r(2)=0.733; p<0.01) for all BC-amended soils. This study clearly demonstrates
      how desorption in the presence of BC is intimately related to pesticide
      biodegradation by the indigenous soil microbiota. BC application to agricultural
      soils can affect the persistence of pesticides as well as the fate of their
      degradation products. This has important implications for the effectiveness of
      pesticides as well as the sequestration of contaminants in soils.

PMID- 22464865
TI  - Construction and evaluation of simulated pilot scale landfill lysimeter in
      Bangladesh.
AB  - This research concentrates the design, construction and evaluation of simulated
      pilot scale landfill lysimeter at KUET campus, Khulna, Bangladesh. Both the
      aerobic and anaerobic conditions having a base liner and two different types of
      cap liner were simulated. After the design of a reference cell, the construction
      of landfill lysimeter was started in January 2008 and completed in July 2008. In
      all construction process locally available civil construction materials were
      used. The municipal solid waste (MSW) of 2800-2985 kg having the total volume of
      2.80 m(3) (height 1.6 m) and moisture content of 65% was deposited in each
      lysimeter by applying required compaction energy. In contrast, both the
      composition in terms of methane (CH(4)), carbon dioxide (CO(2)) and oxygen (O(2))
      as well as the flow rate of landfill gas (LFG) generated from MSW in landfill
      lysimeter were measured and varied significantly in relation to the variation of
      lysimeter operational condition. Moreover, anaerobic lysimeter-C shows the
      highest composition of LFG in compare to the anaerobic lysimeter-B due to the
      providing of lower compaction of cap liner in anaerobic lysimeter-C. Here, it is
      interesting to note that in absence of compacted clay liner (CCL) and hence
      percolation of rainwater that facilitates rapid degradation of MSW in aerobic
      lysimeter-A has resulted in the highest settlement than that of anaerobic
      landfill lysimeter-B and C. Moreover, in case of anaerobic lysimeter-B and C, the
      leachate generation was lower than that of aerobic lysimeter-A due to the
      providing of cap liner in anaerobic lysimeter-B and C, played an important role
      to reduce the percolation of rainwater. The study also reveals that the leachate
      pollution index (LPI) has decreased in relation to the increasing of elapsed
      period as well as the LPI for collection system of aerobic lysimeter-A was higher
      than that of the collection system of anaerobic lysimeter-B and C. Finally, it
      can be depicted that LPI for lysimeter was significantly high and proper
      treatment will be necessary before discharging the lysimeter leachate into the
      water bodies.

PMID- 22464866
TI  - [Sunset (Morgagnian) cataract].

PMID- 22464867
TI  - [Eales disease presenting with vitreous hemorrhage].

PMID- 22464868
TI  - [Asymmetry and stratification of the retinal ganglion cell complex: the Glaucoma
      Triad].

PMID- 22464869
TI  - Letter to the editor: response to Dr Simonsen.

PMID- 22464870
TI  - pH neutralization and influence on mechanical strength in self-adhesive resin
      luting agents.
AB  - OBJECTIVE: The aim of this study was to evaluate if pH-neutralization behavior of
      self-adhesive resin cements has an influence on their mechanical properties.
      METHODS: pH-neutralization, water sorption, solubility and flexural strength of G
      Cem Automix (GCA), G CEM Capsules (GCC), Maxcem Elite (MCE), RelyX Unicem Clicker
      (RXC), RelyX Unicem Maxicap (RXM), RelyX Unicem 2 (RX2), and Speed-Cem (SPC) were
      tested in self-curing mode. Specimen's pH-values were recorded up to 24h with a
      pH-electrode. Water sorption (WS) and solubility (SO) were measured. Flexural
      strength (FS) was evaluated before and after thermocycling (TC) and fracture
      surfaces analyzed under SEM. RESULTS: RX2 (pH(24) 5.89), RXC (pH(24) 5.49) and
      SPC (pH(24) 5.42) showed highest 24h pH-values, followed by GCA (pH(24) 5.34).
      Capsulated products and MCE (pH(24) 3.90) reached lower pH-values. GCC (75.78
      MUg/mm(3)) showed the highest WS followed by MX (69.64 MUg/mm(3)), RXM (64.76
      MUg/mm(3)), GCA (25.86 MUg/mm(3)) and SPC (30.42MUg/mm(3)). Capsulated products
      RXM (56.58 MUg/mm(3)) and GCC (30.94 MUg/mm(3)) presented the highest SO, GCA
      (4.06 MUg/mm(3)) and SPC (4.26 MUg/mm(3)) revealed the lowest. GCA (114.03 MPa)
      had the highest initial FS followed by SPC (79.81 MPa), RXM (41.61 MPa) the
      lowest. FS of all materials decreased significantly after TC except for RXC
      (44.65 MPa) and RX2 (65.92 MPa). FS of GCC (16.47 MPa) and MCE (28.21 MPa)
      decayed the most. A highly linear correlation was observed between percentage
      decrease of FS after TC and 24h pH-values (R(2)=0.861). SIGNIFICANCE: Within the
      limits of this study pH-neutralization behavior has an influence on mechanical
      stability. When using self-adhesive resin luting agents, automix-syringe products
      with improved pH-neutralization behavior should be favored.

PMID- 22464871
TI  - Collaboration and engagement drive Heart Rhythm Society progress.

PMID- 22464872
TI  - Trends in alternative tobacco use among light, moderate, and heavy smokers in
      adolescence, 1999-2009.
AB  - OBJECTIVE: To examine trends in alternative tobacco product (ATP) use (smokeless
      tobacco, cigars, and bidis/cloves) among a national sample of adolescent
      cigarette smokers (light, moderate, and heavy) during 1999-2009. METHOD: A
      secondary analysis of data from the 1999-2009 National Youth Tobacco Survey was
      performed to investigate the tobacco behaviors of 6th through 12th graders
      enrolled in public and private schools in the United States. Long-term trends in
      ATP use were analyzed using logistic regression--controlling for sex, grade, and
      race/ethnicity--and simultaneously assessing linear and higher order time effects
      and their interaction with cigarette smoking status. RESULTS: During 1999-2009,
      increases in smokeless tobacco use and decreases in bidis/cloves use were
      observed across all smoking groups. For cigars, declines were observed for heavy
      and moderate smokers, but levels returned to baseline levels in 2009. Cigar use
      among light smokers was less variable. Rates of any ATP were highest among heavy
      smokers and lowest among light smokers. CONCLUSION: Trends in cigarette and SLT
      use increased dramatically in the past decade, and this increase is evident
      across all cigarette smoker types. Implications for tobacco surveillance,
      prevention and cessation programs, and tobacco control policies are discussed.

PMID- 22464873
TI  - Validation of the delinquent activities scale for incarcerated adolescents.
AB  - PURPOSE: This study examined the validity of the delinquent activities scale
      (DAS), based in part on the self reported delinquency (SRD) scale. METHOD:
      Participants were 190 incarcerated adolescents (85.8% male; average age 17 years)
      at a juvenile correctional facility in the Northeast. While incarcerated, they
      were asked about substance use and delinquent activities in the 1 year prior to
      incarceration, as well as parental, peer, and demographic information. They were
      tracked at three months post-release, given the DAS, and assessed for post
      release substance use. RESULTS: Three factors of the DAS assess general, alcohol
      involved, and marijuana-involved delinquent activities. Principal components
      analysis was used to develop subscales within each factor. Support was found for
      concurrent and predictive incremental validities of these factors and their
      subscales in predicting substance use, with stronger findings for the general and
      the alcohol-involved factors. Subscales related to stealing showed lower validity
      than those related to more aggressive behaviors. CONCLUSIONS: These analyses
      suggest that the factors and empirically derived subscales offer researchers and
      clinicians a psychometrically sound approach for the assessment of adolescent
      misbehaviors.

PMID- 22464874
TI  - Results that matter: structured vs. unstructured self-monitoring of blood glucose
      in type 2 diabetes.
AB  - Self-monitoring of blood glucose (SMBG) is one component of diabetes management.
      SMBG presents information about current glycemic status and provides the ability
      to obtain immediate feedback regarding the impact of behavioral and
      pharmacological interventions on glucose levels. However, SMBG is useful only
      when the glucose information is understood correctly, data are accurately
      interpreted, and results prompt appropriate therapeutic actions. The
      International Diabetes Federation (IDF) recently published guidelines for SMBG
      use in non-insulin treated people with diabetes, recommending that SMBG should be
      used only when patients and/or their clinicians possess the ability and
      willingness to incorporate SMBG monitoring and therapy adjustment into their
      diabetes care plan. If SMBG is used, the IDF also recommends that structured SMBG
      be performed utilizing defined regimens to meet individual needs. Structured SMBG
      can be performed as daily glucose profiles that are representative of daily
      glucose excursions. Measuring preprandial/postprandial blood glucose (bG) levels
      on consecutive or alternating days ("testing in pairs") also provides impactful
      glucose information for daily diabetes management. This article reviews recent
      studies that appropriately utilized structured SMBG as an integral component of
      comprehensive diabetes management and discusses how their findings support the
      IDF recommendations. Our goal is to help clinicians make more informed decisions
      about the value and utility of SMBG in diabetes management.

PMID- 22464875
TI  - Efficient acquisition of high-resolution 4-D diagonal-suppressed methyl-methyl
      NOESY for large proteins.
AB  - The methyl-methyl NOESY experiment plays an important role in determining the
      global folds of large proteins. Despite the high sensitivity of this experiment,
      the analysis of methyl-methyl NOEs is frequently hindered by the limited chemical
      shift dispersion of methyl groups, particularly methyl protons. This makes it
      difficult to unambiguously assign all of the methyl-methyl NOE crosspeaks using 3
      D spectroscopy. The recent development of sparse sampling methods enables highly
      efficient acquisition of high-resolution 4-D spectra, which provides an excellent
      solution to resolving the degeneracy of methyl signals. However, many
      reconstruction algorithms for processing sparsely-sampled NMR data do not provide
      adequate suppression of aliasing artifacts in the presence of strong NOE diagonal
      signals. In order to overcome this limitation, we present a 4-D diagonal
      suppressed methyl-methyl NOESY experiment specifically optimized for ultrasparse
      sampling and evaluate it using a deuterated, ILV methyl-protonated sample of the
      42 kDa Escherichia coli maltose binding protein (MBP). Suppression of diagonal
      signals removes the dynamic range barrier of the methyl-methyl NOESY experiment
      such that residual aliasing artifacts in the CLEAN-reconstructed high-resolution
      4-D spectrum can be further reduced. At an ultrasparse sampling rate of less than
      1%, we were able to identify and unambiguously assign the vast majority of
      expected NOE crosspeaks between methyl groups separated by less than 5 A and to
      detect very weak NOE crosspeaks from methyl groups that are over 7 A apart.

PMID- 22464876
TI  - Serum metabolite concentrations and decreased GFR in the general population.
AB  - BACKGROUND: Metabolites such as creatinine and urea are established kidney
      function markers. High-throughput metabolomic studies have not been reported in
      large general population samples spanning normal kidney function and chronic
      kidney disease (CKD). STUDY DESIGN: Cross-sectional observational studies of the
      general population. SETTING AND PARTICIPANTS: 2 independent samples: KORA F4
      (discovery sample, n = 3,011) and Twins UK (validation sample, n = 984). EXPOSURE
      FACTORS: 151 serum metabolites, quantified by targeted mass spectrometry.
      OUTCOMES AND MEASUREMENTS: Metabolites and their 22,650 ratios were analyzed by
      multivariable-adjusted linear regression for their association with glomerular
      filtration rate (eGFR), estimated separately from creatinine and cystatin C
      levels by CKD-EPI (CKD Epidemiology Collaboration) equations. After correction
      for multiple testing, significant metabolites (P < 3.3 * 10(-4) for single
      metabolites; P < 2.2 * 10(-6) for ratios) were meta-analyzed with independent
      data from the TwinsUK Study. RESULTS: Replicated associations with eGFR were
      observed for 22 metabolites and 516 metabolite ratios. Pooled P values ranged
      from 7.1 * 10(-7) to 1.8 * 10(-69) for the replicated single metabolites.
      Acylcarnitines such as glutarylcarnitine were associated inversely with eGFR (
      3.73 mL/min/1.73 m(2) per standard deviation [SD] increase, pooled P = 1.8 * 10(
      69)). The replicated ratio with the strongest association was the ratio of serine
      to glutarylcarnitine (P = 3.6 * 10(-81)). Almost all replicated phenotypes
      associated with decreased eGFR (<60 mL/min/1.73 m(2); n = 172 cases) in KORA F4:
      per 1-SD increment, ORs ranged from 0.29-2.06. Across categories of a metabolic
      score consisting of 3 uncorrelated metabolites, the prevalence of decreased eGFR
      increased from 3% to 53%. LIMITATIONS: Cross-sectional study design, GFR was
      estimated, limited number of metabolites. CONCLUSIONS: Distinct metabolic
      phenotypes were reproducibly associated with eGFR in 2 separate population
      studies. They may provide novel insights into renal metabolite handling, improve
      understanding of pathophysiology, or aid in the diagnosis of kidney disease.
      Longitudinal studies are needed to clarify whether changes in metabolic
      phenotypes precede or result from kidney function impairment.

PMID- 22464877
TI  - Desensitization offers hope to highly HLA-sensitized patients for a longer life
      expectancy after incompatible kidney transplant.

PMID- 22464878
TI  - Kidney disease education one year after the Medicare Improvement of Patients and
      Providers Act: a survey of US nephrology practices.

PMID- 22464879
TI  - Influence of melatonin or its antagonism on alcohol consumption in ethanol
      drinking rats: a behavioral and in vivo voltammetric study.
AB  - Melatonin, an indoleamine hormone synthesized in the pinealocytes, has been
      implicated as influencing the intake of alcohol in rats. It has been shown that
      this hormone is voltammetrically electroactive at the surface of pretreated
      carbon fiber microelectrodes in vitro and in vivo, in rat cerebral melatonergic
      regions such the pineal gland. The aim of this work consisted in the study of the
      influence of melatonin on spontaneously ethanol drinking or ethanol avoiding rats
      selected throughout a free choice two bottle test. It appeared that only the
      water preferring rats were affected by treatment with the hormone and that in
      vivo voltammetric related levels of melatonin were higher in the pineal gland of
      ethanol drinking rats versus water preferring rats. In addition, when treated
      with the melatonin antagonist GR128107 ethanol drinking rats significantly
      reduced the spontaneous consumption of alcohol.

PMID- 22464880
TI  - Quantification of extracellular levels of corticosterone in the basolateral
      amygdaloid complex of freely-moving rats: a dialysis study of circadian variation
      and stress-induced modulation.
AB  - Corticosterone influences emotion and cognition via actions in a diversity of
      corticolimbic structures, including the amygdala. Since extracellular levels of
      corticosterone in brain have rarely been studied, we characterized a specific and
      sensitive enzymatic immunoassay for microdialysis quantification of
      corticosterone in the basolateral amygdaloid complex of freely-moving rats.
      Corticosterone levels showed marked diurnal variation with an evening (dark
      phase) peak and stable, low levels during the day (light phase). The "anxiogenic
      agents", FG7142 (20 mg/kg) and yohimbine (10 mg/kg), and an environmental
      stressor, 15-min forced-swim, induced marked and sustained (1-3 h) increases in
      dialysis levels of corticosterone in basolateral amygdaloid complex. They
      likewise increased dialysis levels of dopamine and noradrenaline, but not
      serotonin and GABA. As compared to basal corticosterone levels of ~200-300 pg/ml,
      the elevation provoked by forced-swim was ca. 20-fold and this increase was
      abolished by adrenalectomy. Interestingly, stress-induced rises of corticosterone
      levels in basolateral amygdaloid complex were abrogated by combined but not
      separate administration of the corticotrophin releasing factor(1) (CRF(1))
      receptor antagonist, CP154,526, and the vasopressin(1b) (V(1b)) receptor
      antagonist, SSR149,415. Underpinning their specificity, they did not block forced
      swim-induced elevations in dopamine and noradrenaline. In conclusion,
      extracellular levels of corticosterone in the basolateral amygdaloid complex
      display marked diurnal variation. Further, they are markedly elevated by acute
      stressors, the effects of which are mediated (in contrast to concomitant
      elevations in levels of monoamines) by co-joint recruitment of CRF(1) and V(1b)
      receptors.

PMID- 22464881
TI  - Role of angiotensin II in the brain inflammatory events during experimental
      diabetes in rats.
AB  - Hyperglycemia during diabetes is one of the causes of encephalopathy. However,
      diabetes causes chronic inflammatory complications and among them is peripheral
      neuropathy. Since, diabetes is one of the major risk factors for cerebrovascular
      disease, inflammatory process could take place in central nervous system (CNS).
      To test that hypothesis, experiments to determine inflammatory events in CNS
      during streptozotocin-induced diabetes were performed. Diabetes was induced by
      intravenous injection of streptozotocin (STZ). Brain angiotensin II (Ang II),
      monocyte/macrophage (ED-1 positive cells), CD8, the intercellular adhesion
      molecule-1 (ICAM-1), the lymphocyte function-associated antigen-1 (LFA-1) and
      superoxide anion were determined by hystochemical and immunohistochemical
      methods. Nitric oxide (NO), malondialdehyde (MDA) and catalase activity were
      measured in brain homogenates by enzymatic and biochemical methods. This research
      showed increased expressions of Ang II, ICAM-1, LFA-1 and CD8 positive cells in
      diverse zones of cerebrum and cerebellum of diabetic rats (week 8). Treatment of
      diabetic animals with losartan or enalapril reduced the expression of those
      molecules. Values of lipid peroxidation, nitrite content and superoxide anion
      expression remained similar to control rats. Only decreased activity of catalase
      was observed in diabetic animals, but losartan or enalapril failed to modify
      catalase activity. This study suggests the presence of Ang II-mediated brain
      inflammatory events in diabetes probably mediated by AT1 receptors.

PMID- 22464882
TI  - Difference in the norepinephrine levels of experimental and non-experimental rats
      with age in the object recognition task.
AB  - In the present study, we investigated the performance of adult and juvenile rats
      in the Object Recognition Task (ORT). While it is well known that the performance
      of rat in ORT differs with age, the reason for the difference as well as the
      underlying neurotransmitter that may have led to these differences were
      investigated. In the present study, juvenile rats of postnatal day 40-45 (PND 40
      45) and adult rats of postnatal day 60+ (PND 60+) were subjected to a two trial
      ORT. The juvenile rats did not discriminate between the novel object and the
      familiar object, while the adult rats discriminated the novel from the familiar
      object. On estimating brain concentrations of norepinephrine (NE), it was
      observed that the NE level in MTL (medial temporal lobe) of adult experimental
      rats was significantly higher than the adult non-experimental rats. In juvenile
      rats, no significant difference was observed in the NE levels of experimental
      rats in comparison to its non-experimental counterparts. Administration of
      yohimbine (alpha(2A) adrenergic receptor antagonist) enhanced the level of NE in
      juvenile rats and reversed the difference seen with age. From the present study,
      we conclude that the deficit in memory seen is likely due to the difference in NE
      levels with task and this can be reversed by yohimbine which enhance NE levels.

PMID- 22464883
TI  - Relative imbalances in the expression of catechol-O-methyltransferase and
      cytochrome P450 in breast cancer tissue and their association with breast
      carcinoma.
AB  - OBJECTIVE: To investigate the expression levels of genes encoding phase I and
      phase II estradiol-metabolizing enzymes, and their association with breast cancer
      risk in Chinese women. METHODS: The mRNA expression levels of cytochrome P450
      (CYP) 1A1, 1B1 and 3A4 and catechol-O-methyltransferase (COMT) were examined in
      the breast tumor tissues, matched adjacent non-tumor tissues and the tissues with
      benign breast disease (BBD) by fluorescent quantitative real-time PCR. RESULTS:
      Compared to BBD tissue, the mRNA expression of CYP1A1, CYP1B1 and CYP3A4
      significantly reduced by 81.8%, 77.5%, and 85.6%, respectively, in the breast
      tumor tissue and by 27.2%, 38.8%, and 51.3%, respectively, in the adjacent non
      tumor tissue in average (p<0.0001). COMT mRNA was 6.9 and 6.4 fold higher in the
      breast tumor and match non-tumor tissue (p<0.0001) than in the BBD, respectively.
      The level of COMT detected in pre-menopausal group and lymph nodal stage N1-N2
      group was lower than that in post-menopausal group (p=0.0292) and N0 group
      (p=0.0389), respectively. CONCLUSION: Significantly deceased expression of
      estradiol-metabolizing enzymes might result in the excess exposure of
      intratumoural E2, which could be one of the important risk factors for breast
      cancer. Significantly elevated COMT expression suggested that COMT could play a
      key role in breast tumor formation.

PMID- 22464884
TI  - Correlative light and scanning electron microscopy of the same sections gives new
      insights into the effects of pectin lyase on bordered pit membranes in Pinus
      radiata wood.
AB  - Bordered pits are structures in the cell walls of softwood tracheids which permit
      the movement of water between adjacent cells. These structures contain a central
      pit membrane composed of an outer porous ring (margo) and an inner dense and
      pectin-rich disc (torus). The membrane is overarched on each side by pit borders.
      Pits may be aspirated, a condition where the torus seals against the pit border,
      effectively blocking the pathway between cells. In living trees this maintains
      overall continuity of water conduction in xylem by sealing off tracheids
      containing air. Drying of timber results in further pit aspiration, which reduces
      wood permeability to liquid treatment agents such as antifungal chemicals. One
      possible way to increase permeability is by treating wood with pectin lyase to
      modify or remove the torus. The effectiveness of this treatment was initially
      evaluated using light microscopy (LM) of toluidine blue stained wood. Pectic
      material is coloured pink-magenta with this stain, and loss of this colour after
      treatment has been interpreted as indicating destruction of the torus. However,
      correlative light (LM) and scanning electron (SEM) microscopic observations of
      identical areas of toluidine blue stained sections revealed that many unstained
      pits had intact but modified tori when viewed with SEM. These observations
      indicate that LM alone is not sufficient to evaluate the effects of pectin lyase
      on pit membranes in wood. Combining LM and SEM gives more complete information.

PMID- 22464885
TI  - Mechanisms-based classifications of musculoskeletal pain: part 3 of 3: symptoms
      and signs of nociceptive pain in patients with low back (+/- leg) pain.
AB  - As a mechanisms-based classification of pain 'nociceptive pain' (NP) refers to
      pain attributable to the activation of the peripheral receptive terminals of
      primary afferent neurones in response to noxious chemical, mechanical or thermal
      stimuli. The symptoms and signs associated with clinical classifications of NP
      have not been extensively studied. The purpose of this study was to identify
      symptoms and signs associated with a clinical classification of NP in patients
      with low back (+/- leg) pain. Using a cross-sectional, between-subjects design;
      four hundred and sixty-four patients with low back (+/- leg) pain were assessed
      using a standardised assessment protocol after which their pain was assigned a
      mechanisms-based classification based on experienced clinical judgement.
      Clinicians then completed a clinical criteria checklist indicating the
      presence/absence of various symptoms and signs. A regression analysis identified
      a cluster of seven clinical criteria predictive of NP, including: 'Pain localised
      to the area of injury/dysfunction', 'Clear, proportionate mechanical/anatomical
      nature to aggravating and easing factors', 'Usually intermittent and sharp with
      movement/mechanical provocation; may be a more constant dull ache or throb at
      rest', and the absence of 'Pain in association with other dysesthesias', 'Night
      pain/disturbed sleep', 'Antalgic postures/movement patterns' and 'Pain variously
      described as burning, shooting, sharp or electric-shock-like'. This cluster was
      found to have high levels of classification accuracy (sensitivity 90.9%, 95% CI:
      86.6-94.1; specificity 91.0%, 95% CI: 86.1-94.6). Pattern recognition of this
      empirically-derived cluster of symptoms and signs may help clinicians identify an
      assumed dominance of NP mechanisms in patients with low back pain disorders.

PMID- 22464886
TI  - Acute low back pain information online: an evaluation of quality, content
      accuracy and readability of related websites.
AB  - The internet is increasingly being used as a source of health information by the
      general public. Numerous websites exist that provide advice and information on
      the diagnosis and management of acute low back pain (ALBP), however, the accuracy
      and utility of this information has yet to be established. The aim of this study
      was to establish the quality, content and readability of online information
      relating to the treatment and management of ALBP. The internet was systematically
      searched using Google search engines from six major English-speaking countries.
      In addition, relevant national and international low back pain-related
      professional organisations were also searched. A total of 22 relevant websites
      was identified. The accuracy of the content of the ALBP information was
      established using a 13 point guide developed from international guidelines.
      Website quality was evaluated using the HONcode, and the Flesch-Kincaid Grade
      level (FKGL) was used to establish readability. The majority of websites lacked
      accurate information, resulting in an overall mean content accuracy score of
      6.3/17. Only 3 websites had a high content accuracy score (>14/17) along with an
      acceptable readability score (FKGL 6-8) with the majority of websites providing
      information which exceeded the recommended level for the average person to
      comprehend. The most accurately reported category was, "Education and
      reassurance" (98%) while information regarding "manipulation" (50%), "massage"
      (9%) and "exercise" (0%) were amongst the lowest scoring categories. These
      results demonstrate the need for more accurate and readable internet-based ALBP
      information specifically centred on evidence-based guidelines.

PMID- 22464888
TI  - Altered expression of CX3CL1 in patients with epilepsy and in a rat model.
AB  - Chemokine C-X3-C motif ligand 1 (CX3CL1, alias fractalkine), is highly expressed
      in the central nervous system and participates in inflammatory responses. Recent
      studies indicated that inflammatory processes within the brain constitute a
      common and crucial mechanism in the pathophysiological characteristics of
      epilepsy. This study investigated the expression pattern of CX3CL1 in epilepsy
      and its relationship with neuronal loss. Double immunolabeling, IHC, and
      immunoblotting results showed that CX3CL1 expression was up-regulated in the
      temporal neocortex of patients with temporal lobe epilepsy. In a rat model of
      epilepsy, CX3CL1 up-regulation began 6 hours after epilepsy, with relatively high
      expression for 60 days. In addition, ELISA revealed that the concentrations of
      CX3CL1 in cerebrospinal fluid and serum were higher in epileptic patients than in
      patients with neurosis but lower than in patients with inflammatory neurological
      diseases. Moreover, H&E staining demonstrated significant neuronal loss in the
      brains of epileptic patients and in the rat model. Finally, the expression of
      tumor necrosis factor-related apoptosis-inducing ligand was significantly
      increased in both patients and the animal model, suggesting that tumor necrosis
      factor-related apoptosis-inducing ligand may play a role in CX3CL1-induced cell
      death. Thus, our results indicate that CX3CL1 may serve as a possible biomarker
      of brain inflammation in epileptic patients.

PMID- 22464889
TI  - Arteriolar lesions in renal transplant biopsies: prevalence, progression, and
      clinical significance.
AB  - Arteriolar hyalinosis in kidney transplants is considered the histopathologic
      hallmark of chronic calcineurin inhibitor (CNI) toxicity. However, the lesion is
      not specific. We assessed prevalence, progression, and clinical significance of
      arteriolar lesions in 1239 renal transplant sequential protocol biopsy samples
      and 408 biopsy for cause samples in 526 patients. Associations between arteriolar
      lesions and presumed risk factors, concomitant histopathologic lesions,
      demographic factors, and graft function were evaluated. The frequency of
      arteriolar lesions was stable during the first 2 years after transplantation, and
      increased thereafter (14.8% at 6 months versus 48.6% at >2 years; P < 0.0001). We
      were unable to find associations with diabetes, hypertension, or CNI therapy.
      However, patients with early arteriolar lesions received grafts from older donors
      (mean +/- SD age, 54.4 +/- 13.4 years versus 43.1 +/- 16.6 years; P < 0.0001),
      and had inferior graft function (estimated glomerular filtration rate 55 +/- 21
      mL/min versus 63 +/- 24 mL/min at 6 weeks, 53 +/- 19 mL/min versus 60 +/- 23
      mL/min at 1 year, and 49 +/- 19 mL/min versus 59 +/- 22 mL/min at 2 years; P <
      0.05). Evaluation of late biopsy samples from patients not receiving CNI therapy
      revealed a high prevalence of AH without clear-cut identifiable underlying cause.
      Reproducibility of arteriolar lesions was at best moderate (kappa <= 0.62).
      Sampling error in sequential biopsy samples was frequent. In conclusion, in
      samples from sequential protocol biopsies and biopsies for cause in individual
      patients, arteriolar lesions in renal transplants not only increase over time
      without being specific for CNI toxicity but are affected by sampling error and
      limited reproducibility.

PMID- 22464890
TI  - [Rare diseases: Innovation laboratories for human health].

PMID- 22464891
TI  - [A comparison of self-esteem in alcohol-dependent women and women who have become
      abstinent, against a control group].
AB  - INTRODUCTION: Women's addiction to alcohol remains a taboo subject, whereas one
      third of alcohol-dependent people are female. Social representations concerning
      them are very unfavorable. Their alcoholism is usually accompanied by strong
      feelings of guilt, depreciation and lowered self-esteem. There is little existing
      work about self-esteem in women who have become abstinent. This study's goal is
      to compare the self-esteem of women who are alcohol-dependent and the self-esteem
      of women who have become abstinent in various domains (social, familial,
      professional). METHODS: The sample contained 71 women divided into three groups:
      31 alcohol-dependent women (average age of 44.9); 20 alcohol-dependent women who
      had become abstinent for at least two months (average age of 44.7) and 20 women
      who formed the control group (average age of 44.4). The material was put together
      from the Self-Esteem Inventory (SEI, adult version of Coopersmith 1981). It
      includes 58 items divided into four sub-categories (general self-esteem, social,
      familial and professional) and a scale for falsehoods. The SEI was self
      administered. The statistics were produced entirely with non-parametric tests:
      Mann-Whitley U Test for the comparison of two independent samples and Kruskal
      Wallis Anova for the comparison of three independent samples. RESULTS: A
      significant difference was found for general self-esteem (P=0.001), familial
      (P=0.01) and professional (P=0.03) between the three groups of women (alcohol
      dependent, alcohol-dependent who had become abstinent and women from the control
      group). There was no statistical difference for social self-esteem or the lying
      scale. There was a difference between alcohol-dependent women and the control
      group in general self-esteem (P=0.0001), familial self-esteem (P=0.01) and
      professional self-esteem (P=0.002), as well as between women who had become
      abstinent and women from the control group in general self-esteem (P=0.02),
      familial self-esteem (P=0.005) and professional self-esteem (P=0.07; ns). No
      difference was found between alcohol-dependent women and women who had become
      abstinent. CONCLUSION: This study has shown evidence that general, familial and
      professional self-esteem drops in alcohol-dependent women and in women who had
      become abstinent compared to a general population. There was no proof of any
      difference of self-esteem in women who had become abstinent and alcohol-dependent
      women, although abstinent women seemed to have better general and professional
      self-esteem while their familial self-esteem seemed to be lower. This study begs
      the question about self-esteem in women who have become abstinent suggests that
      self-esteem should be integrated into their treatment.

PMID- 22464892
TI  - [Cohorts and registers: Which public/private partnerships to choose?].

PMID- 22464893
TI  - [Proposal of HIV, HBV and HCV targeted screening: short period feasibility study
      in a free-access outpatient medical structure].
AB  - OBJECTIVES: In France, patients coming from sub-Saharan Africa, French Indies and
      French Guiana are frequently missed HIV, HBV and HCV diagnosis, despite high
      prevalence of these infections. METHODS: Targeted proposal of HIV, HBV and HCV
      screening, using sensitive enzyme immunoassays, to any adult patient originating
      of the above mentioned areas, with/without medical insurance, consulting for a
      medical issue in outpatients' department. Monocentric prospective study in a
      hospital in Paris during 28 consecutive days in 2010. RESULTS: Among the 272
      eligible patients, 166 were tested (patients' acceptance: 61%). 180/272 (66%)
      alleged being tested previously for HIV, women (66/87, 76%) more frequently than
      men (114/185, 62%), P=0.02. Patients' acceptance seemed higher in patients
      mentioning no previous test than in patients reporting previous test. Among the
      patients who refused being tested, reporting a previous negative HIV test, more
      than a quarter has been tested more than 1 year ago. Among the 166 tested
      patients, 120 (72%) came back to get their results, men (89/113, 79%) more
      frequently than women (31/53, 58.5%), P=0.009; recently metropolitan patients
      more frequently than longer metropolitan patients, P=0.01; patients without any
      job more frequently than patients with a job, P=0.01. Three (1.8%) HIV tests
      returned positive; HBsAg was positive in 13 (7.8%) patients; 54 patients (32.7%)
      had a negative hepatitis B screening (anti-HBcAb+HBsAg+anti-HBsAb), attesting to
      sensitivity to this infection, only 18 patients (10.9%) showed isolated anti
      HBsAb at protective levels. Eighty-one patients (49.1%) exhibited anti-HBcAb,
      confirming the high prevalence of HBV infection in the areas the patients came
      from. Six patients (3.6%) had anti-HCVAb. There was no co-infection. CONCLUSION:
      Targeted HIV, HBV and HCV screening to patients coming from high prevalence areas
      in outpatients' department appears a very cost-effective strategy.

PMID- 22464894
TI  - [Sensitive troponin: A new definition of acute myocardial infarction?].
AB  - Cardiac troponins, which are structural proteins unique to the heart, are
      sensitive and specific biochemical markers of myocardial damage. The measurement
      of cardiac troponins plays a central role for diagnosis of acute myocardial
      infarction. Introduction of high-sensitivity troponin increases sensitivity to
      identify patients with acute myocardial infarction. It can substantially improve
      the early diagnosis of acute myocardial infarction, particularly in patients with
      a recent onset of chest pain, and provide better prognostic information.

PMID- 22464895
TI  - [Evolution of the accredited continuing education after Patient Safety Strategy
      implementation].
AB  - OBJECTIVE: [corrected] To analyse the evolution of continuing education
      activities in the main areas of the Strategy for Patient Safety of the Andalusian
      Accreditation Model. MATERIAL AND METHODS: An observational study was carried out
      on continuing education activities related to patient safety according to the
      Andalusian Accreditation Model, during 2003-2010. Results were evaluated
      (Fisher's exact test) by SPSS v.16 program. RESULTS: A total of 12,975 health
      professional activities were accredited, of which 1,002 (7.7%) activities and
      13,413 meetings were related to one or more of safety lines. The main target
      groups of this training were Nursing with 4,763 meetings (35.5%), Medicine with
      4,090 meetings (30.5%), and Medical Technicians with 1,963 meetings (14.6%).
      CONCLUSIONS: The implementation and consolidation of the Strategy for Patient
      Safety, has encouraged the development of accredited continuing education
      activities related to safety, as well as an improvement in the qualitative value
      of this activities.

PMID- 22464897
TI  - The importance of transurethral resection in managing patients with urothelial
      cancer in the bladder: proposal for a transurethral resection of bladder tumor
      checklist.

PMID- 22464896
TI  - Effects of deer density on tick infestation of rodents and the hazard of tick
      borne encephalitis. I: empirical assessment.
AB  - Tick borne encephalitis (TBE) is endemic to eastern and central Europe with broad
      temporal and spatial variation in infection risk. Although many studies have
      focused on understanding the environmental and socio-economic factors affecting
      exposure of humans to TBE, comparatively little research has been devoted to
      assessing the underlying ecological mechanisms of TBE occurrence in enzootic
      cycles, and therefore TBE hazard. The aim of this study was to evaluate the
      effect of the main ungulate tick hosts on the pattern of tick infestation in
      rodents and TBE occurrence in rodents and questing adult ticks. In this empirical
      study, we considered three areas where endemic human TBE occurs and three control
      sites having no reported human TBE cases. In these six sites located in Italy and
      Slovakia, we assessed deer density using the pellet group count-plot sampling
      technique, collected questing ticks, live-trapped rodents (primarily Apodemus
      flavicollis and Myodes glareolus) and counted ticks feeding on rodents. Both
      rodents and questing ticks were screened for TBE infection. TBE infection in
      ticks and rodents was positively associated with the number of co-feeding ticks
      on rodents and negatively correlated with deer density. We hypothesise that the
      negative relationship between deer density and TBE occurrence on a local scale
      (defined by the minimum overlapping area of host species) could be attributed to
      deer (incompetent hosts) diverting questing ticks from rodents (competent hosts),
      know as the 'dilution effect hypothesis'. We observed that, after an initial
      increase, the number of ticks feeding on rodents reached a peak for an
      intermediate value of estimated deer density and then decreased. Therefore, while
      at a regional scale, tick host availability has already been shown to be directly
      correlated with TBE distribution, our results suggest that the interactions
      between deer, rodents and ticks are much more complex on a local scale,
      supporting the possibility of a dilution effect for TBE.

PMID- 22464899
TI  - Elderly patients with aneurysmal subarachnoid hemorrhage: Coils but also clips.
AB  - The ageing of the population in good health or without severe morbidity expose
      them to the occurrence of a subarachnoid hemorrhage (SAH) and requires effective
      management. Currently, the pertinence of cerebral aneurysm treatment by clipping
      or coiling is accepted for patients in the 8th or 9th decade of life, and the
      risk of postoperative morbidity induced by our therapeutic alternative must be
      carefully assessed. In these decades, the female/male sex ratio for aneurysmal
      SAH was greater in female who had a 1.6 times higher ratio than in male. The
      initial clinical status did not appear worse with age despite the frequent
      severity of bleeding observed on CT scan probably due to the large subarachnoid
      space. The aneurysm distribution and size were similar to those classically
      reported in the global population. The endovascular (EV) coiling appears as the
      first option with a favorable outcome rate estimated at 48% to 63%. Nevertheless,
      the benefit of EV coiling compared to microsurgical clipping for treatment of
      ruptured aneurysm in the elderly has not been demonstrated in a large randomized
      study. This is the reason why the vascular section of the French Society of
      Neurosurgery developed a prospective and randomized study of the aneurysmal SAH
      (PHRC 2007-042/HP) on the elderly patients.

PMID- 22464902
TI  - Aneurysm recurrence after endovascular treatment.
AB  - While the risk of haemorrhage related to aneurysm recurrence after endovascular
      treatment is not well established, concerns about it lead to imaging follow-up
      and further treatments that have a real impact on patients' lives. These concerns
      are also the motor of technological developments aiming at reducing the
      recurrence rate but also having the potential to increase the complication rate
      of initial treatment. This article will address some issues related to aneurysm
      recurrence in view of the actual literature.

PMID- 22464903
TI  - [Indications and surgical treatments for failed coiled aneurysms].
AB  - The possibility of treating intra-cranial aneurysms (ICA) through an endovascular
      approach is a great progress. But, as any technique, it has its own limitations.
      Multidisciplinary neurovascular teams are regularly confronted with ICA where
      embolization is a poor option or even failed (a residue of more than 5% at six
      months follow-up or after recanalization). Another potential failure is a coil
      extrusion into the parent vessel with thrombo-embolic risks. Our team and others
      in the world developed strategies to manage these complex cases. After a brief
      review of the literature, we describe our experience and present a modified
      Gurian classification. This classification allows a better identification of the
      various failed coiled aneurysms types and their potential surgical treatments.

PMID- 22464905
TI  - Replication of leaving Las Vegas in the #2 travel destination, Orlando, Florida.
      A commentary on Wray, Miller, Gurvey, Carroll and Kawachi (2008).

PMID- 22464906
TI  - Socioeconomic disadvantage in adolescent women and metabolic syndrome in mid
      adulthood: an examination of pathways of embodiment in the Northern Swedish
      Cohort.
AB  - Research indicates that disadvantaged socioeconomic status in childhood or
      adolescence increases specifically women's risk for developing metabolic syndrome
      in adulthood. Construing this observation as an expression of embodiment, the
      present study aims at examining the 'social chain of risk' and the 'reproduction'
      hypotheses as pathways of this embodiment. Participants were all women in the
      Northern Swedish Cohort, a 27-year prospective Swedish cohort, with data
      collection in 1981 at age 16 years (n = 1083, 506 women), and follow-up at age
      21, 30 and 43 (n = 482 women) years. The analytical sample was n = 399 women (79%
      of the original cohort). Socioeconomic disadvantage was defined as parental
      manual occupation at age 16, and metabolic syndrome according to standardized
      criteria at age 43. The social chain of risk was operationalized as accumulated
      social and material adversities at age 16, 21, 30 and 43 years, and reproductive
      factors by age at menarche, early childbearing (before age 22), and number of
      children at age 43. In logistic regression with metabolic syndrome as the
      outcome, the OR for adolescent socioeconomic status was rendered non-significant
      and reduced by 21.6% after adjustment for cumulative adversity over the life
      course. Of the reproductive factors, only age at menarche lead to an OR reduction
      at all (by 4.1%). Our study suggests that women's embodiment of socioeconomic
      disadvantage during upbringing is partly explained by adversity over the
      subsequent life course. Future studies should incorporate the living conditions
      of women over the life course as a possible pathway whereby early life
      socioeconomic conditions are embodied.

PMID- 22464908
TI  - The unbearable lightness of citizens within public deliberation processes.
AB  - There is a growing literature examining the involvement of citizens in health
      policymaking. While determining what form such involvement should take and who
      should participate is of particular interest to policymakers and researchers, the
      current ontological understanding of what a citizen is suffers from "lightness."
      This essay thus seeks to provide more depth by shedding light on the ways in
      which individuals define what "being" a citizen means for them and choose to
      embody or not such a role. Inspired by a four-year ethnographic study of a
      Canadian science/policy network in genetics, which integrated citizens into its
      operation, this paper provides four biographical sketches that portray the
      complexity and richness of what these individuals were "made of." We reflect on
      how they sought to make sense of their participation in the network by drawing on
      a repertoire of cultural, relational and cognitive resources and on their lived
      experience. Their capacity to "be" a participant and to be acknowledged as such
      by the others was shaped by their values and interests and by the contributions
      they sought to realise throughout their participation. Our discussion suggests
      that the quest for the "ordinary" citizen is misleading. Instead, acknowledging
      the sociological concreteness of citizenship and understanding how it may be
      embodied and exercised should be a key focus in public involvement theory and
      practice in health care.

PMID- 22464909
TI  - A study of environmental influences on the well-being of individuals with
      psychiatric disabilities in Philadelphia, PA.
AB  - The influence of community-level indicators in understanding mental health has
      been of interest since the seminal work of Faris and Dunham (1939). The emergence
      of Geographic Information Systems (GIS), and concepts such as social capital and
      recovery add new tools and concepts for further explorations in this area. This
      correlational study uses an innovative GIS approach to examine the relative
      contribution of community indicators, such as crime, unemployment, social
      capital, and individual-level sociodemographic characteristics, such as gender,
      age, and experience of homelessness, to the well-being and recovery of 378
      individuals diagnosed with either major depression or a schizophrenia-spectrum
      disorder residing in an urban environment in the Northeast United States. Results
      indicate that community-level indicators are only marginally correlated with well
      being, including self-reported symptoms, quality of life, empowerment, and
      recovery. These associations are further reduced when considering individuals'
      sociodemographic characteristics, which appear to explain a greater amount of
      variability in well-being and recovery. Contrary to expectations, these results
      suggest that community indicators may not have a major impact on individuals who
      have already developed a significant psychiatric condition, at least in the
      domains studied, and that personal factors play a more significant role. These
      findings further advance our knowledge about the relationship between "place" and
      personal factors on mental health and wellness.

PMID- 22464910
TI  - The protective role of supportive friends against bullying perpetration and
      victimization.
AB  - A crossed-lagged regression model was tested to investigate relationships between
      friendship support, bullying involvement, and its consequences during
      adolescence. Students, 12-16 years (N = 880), were administered questionnaires
      twice, one year apart. Using structural equation modeling, a model was specified
      and higher levels of support from friends were related to lower levels of
      bullying and victimization one year later. Additionally, a bidirectional
      relationship between victimization and depression was found, and greater property
      crimes commission was related to higher levels of future bullying. These findings
      support the 'friendship protection hypothesis' and suggest the quality of support
      in friendships can protect against bullying victimization and perpetration. Prior
      research has shown that friendships can protect against victimization; however
      this is one of the few longitudinal studies to focus on the quality of
      friendship, rather than other characteristics of the friends. It is suggested
      that interventions should focus on increasing perceptions of support within
      existing friendships.

PMID- 22464911
TI  - Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted
      hypofractionated intensity-modulated radiation therapy for localized
      adenocarcinoma of the prostate.
AB  - PURPOSE: A Phase I/II protocol was conducted to examine the toxicity and efficacy
      of the combination of intensity-modulated radiation therapy (IMRT) with a single
      fraction high-dose-rate (HDR) brachytherapy implant. METHODS AND MATERIALS: From
      2001 through 2006, 26 consecutive patients were treated on the trial. The primary
      objective was to demonstrate a high rate of completion without experiencing a
      treatment-limiting toxicity. Eligibility was limited to patients with T stage
      <=2b, prostate-specific antigen (PSA) <=20, and Gleason score <=7. Treatment
      began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the
      peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a
      normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node.
      The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose
      >128Gy (alpha/beta=3). Patients whose pretreatment PSA was >=10ng/mL, Gleason
      score 7, or stage >=T2b received short-term androgen ablation. RESULTS: Median
      followup was 53 months (9-68 months). There were no biochemical failures by
      either the American Society of Therapeutic Radiology and Oncology or the Phoenix
      definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed
      the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was
      3.8% consisting of a urethral stricture. There was no other Grade 3 or 4
      genitourinary or gastrointestinal toxicities. CONCLUSIONS: Single-fraction HDR
      boosted IMRT is a safe effective method of dose escalation for localized prostate
      cancer.

PMID- 22464912
TI  - Mucin-producing adenocarcinoma arising in an atrial myxoma.
AB  - We describe the unique autopsy findings of a patient who died of a metastasizing
      giant right atrial adenocarcinoma containing few areas of typical myxoma. That no
      mucin-producing extracardiac tumor was detected pointed to the atrial
      adenocarcinoma as being the primary. We hypothesize that the adenocarcinoma may
      have developed from coexistent bland glandular structures within the myxoma.

PMID- 22464913
TI  - Antigenic stimulation induces recombination activating gene 1 and terminal
      deoxynucleotidyl transferase expression in a murine T-cell hybridoma.
AB  - Secondary rearrangements of the T cell receptor (TCR) represent a genetic
      correction mechanism which changes T cell specificity by re-activating V(D)J
      recombination in peripheral T cells. Murine T-cell hybridoma A1.1 was employed to
      investigate whether antigenic stimulation induced re-expression of recombinase
      genes and altered TCR Vbeta expression. Following repeated antigenic stimulation,
      A1.1 cells were induced to re-express recombination activating gene (RAG)1 and
      terminal deoxynucleotidyl transferase (TdT) which are generally considered
      prerequisite to TCR gene rearrangement. Accompanied with the significant changes
      in TCR mRNA levels over time, it is suggested that secondary rearrangements may
      be induced in A1.1 cells, which represent a mature T cell clone capable of re
      expressing RAG genes and possesses the prerequisite for secondary V(D)J
      rearrangement.

PMID- 22464914
TI  - Tolerogenic dendritic cells generated by RelB silencing using shRNA prevent acute
      rejection.
AB  - It is well known that adoptive transfer of donor-derived tolerogenic dendritic
      cells (DCs) helps to induce immune tolerance. RelB, one of NF-kappaB subunits, is
      a critical element involved in DC maturation. In the present study, our results
      showed tolerogenic DCs could be acquired via silencing RelB using small
      interfering RNA. Compared with imDCs, the tolerogenic DCs had more potent ability
      to inhibit mixed lymphocyte reaction (MLR) and down-regulate Th1 cytokines and
      prompt the production of Th2 cytokines. They both mediated immune tolerance via
      the increased of T cell apoptosis and generation of regulatory T cells.
      Administration of donor-derived tolerogenic DCs significantly prevented the
      allograft rejection and prolonged the survival time in a murine heart
      transplantation model. Our results demonstrate donor-derived, RelB-shRNA induced
      tolerogenic DCs can significantly induce immune tolerance in vitro and in vivo.

PMID- 22464916
TI  - Integrated allele-specific polymerase chain reaction-capillary electrophoresis
      microdevice for single nucleotide polymorphism genotyping.
AB  - An integrated allele-specific (AS) polymerase chain reaction (PCR) and capillary
      electrophoresis (CE) microdevice has been developed for multiplex single
      nucleotide polymorphism (SNP) genotyping on a portable instrumentation, which was
      applied for on-site identification of HANWOO (Korean indigenous beef cattle).
      Twelve sets of primers were designed for targeting beef cattle's eleven SNP loci
      for HANWOO verification and one primer set for a positive PCR control, and the
      success rate for identification of HANWOO was demonstrated statistically. The AS
      PCR and CE separation for multiplex SNP typing was carried out on a glass-based
      microchip consisting of four layers: a microchannel plate for microfluidic
      control, a Pt-electrode plate for a resistance temperature detector (RTD), a
      poly(dimethylsiloxane) (PDMS) membrane and a manifold glass for microvalve
      function. The operation of the sample loading, AS PCR, microvalve, and CE on a
      chip was automated with a portable genetic analyzer, and the laser-induced
      fluorescence detection was performed on a miniaturized fluorescence detector. The
      blind samples were correctly identified as a HANWOO by showing one or two
      amplicon peaks in the electropherogram, while the imported beef cattle revealed
      more than five peaks. Our genetic analysis platform provides rapid, accurate, and
      on-site multiplex SNP typing.

PMID- 22464915
TI  - An exonuclease III and graphene oxide-aided assay for DNA detection.
AB  - We have developed a novel DNA assay based on exonuclease III (ExoIII)-induced
      target recycling and the fluorescence quenching ability of graphene oxide (GO).
      This assay consists of a linear DNA probe labeled with a fluorophore in the
      middle. Introduction of target sequence induces the exonuclease III catalyzed
      probe digestion and generation of single nucleotides. After each cycle of
      digestion, the target is recycled to realize the amplification. Finally, graphene
      oxide is added to quench the remaining probes and the signal from the resulting
      fluorophore labeled single nucleotides is detected. With this approach, a sub
      picomolar detection limit can be achieved within 40 min at 37 degrees C. The
      method was successfully applied to multicolor DNA detection and the analysis of
      telomerase activity in extracts from cancer cells.

PMID- 22464917
TI  - Electrically contacted enzyme based on dual hairpin DNA structure and its
      application for amplified detection of Hg2+.
AB  - In the present study, based on a dual hairpin DNA structure, a novel system of
      electrically contacted enzyme and its signal amplification for ultrasensitive
      detection of Hg(2+) was demonstrated. In the presence of Hg(2+), with the
      interaction of thymine-Hg(2+)-thymine (T-Hg(2+)-T), DNA sequence dully labeled
      with ferrocene (Fc) at 5' end and horseradish peroxidase (HRP) at 3' end,
      hybridized to the capture probe and formed the dual hairpin structure on the
      electrode. Fc unit acts as a relay that electrically contacts HRP with the
      electrode and activates the bioelectrocatalyzed reduction of H(2)O(2). And based
      on the bioelectrocatalyzed signal amplification of the presented system, Hg(2+)
      could be quantitatively detected in the range of 10(-10)-10(-6)M with a low
      detection limit of 52 pM. And it also demonstrated excellent selectivity against
      other interferential metal ions.

PMID- 22464918
TI  - Layer-by-layer assembly of chemical reduced graphene and carbon nanotubes for
      sensitive electrochemical immunoassay.
AB  - In this work, uniform and stable multi-walled carbon nanotubes (MWCT) and
      chemically reduced graphene (GR) composite electrode interface was fabricated by
      using layer-by-layer assembly method. The performances of these GR-MWCT assembled
      electrode interfaces were studied by electrochemical impedance spectroscopy (EIS)
      and cyclic voltammetry (CV). It was demonstrated that the assembled composite
      film significantly improved the interfacial electron transfer rate compared with
      that of GR or MWCT modified electrode. Based on the GR-MWCT assembled interface,
      a sandwich-type electrochemical immunosensor was constructed using human IgG as a
      model target. In this assay, human IgG was fixed as the target antigen, the HRP
      conjugated IgG as the probing antibody and hydroquinone as the electron mediator.
      The detection limit of the immunosensor was 0.2 ng mL(-1) (signal-to-noise ratio
      of 3). A good linear relationship between the current signals and the
      concentrations of Human IgG was achieved from 1 ng mL(-1) to 500 ng mL(-1).
      Moreover, this electrochemical immunosensor exhibited excellent selectivity,
      stability and reproducibility, and can be used to accurately detect IgG
      concentration in human serum samples. The results suggest that the
      electrochemical immunosensor based on GR-MWCT assembled composite will be
      promising in the point-of-care diagnostics application of clinical screening of
      multiple diseases.

PMID- 22464919
TI  - Ovarian vein thrombosis.
AB  - Ovarian vein thrombosis is a well-known but rare entity, which can occur during
      the post-partum period. This condition has also been associated with inflammatory
      and malignant processes within the pelvis. Untreated, complications of ovarian
      vein thrombosis can be significant due to the associated sepsis and risk of
      pulmonary embolism. Diagnosis can be made with confidence using ultrasound,
      computed tomography or magnetic resonance imaging. Treatment of ovarian vein
      thrombosis is particularly important in the post-partum patients, with
      anticoagulation therapy being the current recommendation.

PMID- 22464920
TI  - Current and potential renal applications of contrast-enhanced ultrasound.
AB  - The combination of microbubble technology and complementary ultrasound techniques
      has resulted in the development of contrast-enhanced ultrasound (CEUS) and,
      although initial clinical applications largely focussed on the liver, these are
      now becoming more diverse. With regard to the kidney, it is a safe, well
      tolerated, and reproducible technique, and in selected cases, can obviate the
      need for computed tomography or magnetic resonance imaging. A clear advantage is
      the absence of nephrotoxicity. With respect to the current and potential renal
      applications, it is a useful technique in the evaluation of pseudotumours, acute
      pyelonephritis, renal tumours, cystic lesions, vascular insults, and renal
      transplantation. It may also be of value for monitoring the kidney following anti
      angiogenic treatment or nephron-sparing interventional techniques for renal
      tumours. Assessment of microvascular perfusion using time-intensity curves is
      also likely to have further far-reaching applications in the kidney as well as
      other organs.

PMID- 22464921
TI  - Scrotal calcification in a symptomatic paediatric population: Prevalence,
      location, and appearance in a cohort of 516 patients.
AB  - AIM: To describe the prevalence of all forms of scrotal calcification within a
      symptomatic paediatric population and to compare this with previous reported data
      in paediatric and adult populations. MATERIALS AND METHODS: A retrospective
      analysis of testicular ultrasound examinations performed in a single institution
      over a 55 month period. All examinations were performed by experienced operators
      using high-frequency linear array transducers. Types of scrotal calcification and
      position were recorded with all available images analysed by experienced
      radiologists. RESULTS: A total 516 male patients under the age of 19 years (mean
      age 10.5 years) were included. The prevalence of testicular microlithiasis (TM)
      was 8.7% and the prevalence of non-TM macrocalcification was 0.4%. 2.3% of the
      patients had scrotal pearls and 0.2% had epididymal calcification recorded. No
      other form of calcification was identified. A single patient had a co-existing
      testicular tumour and TM at examination. CONCLUSION: The prevalence of TM in the
      symptomatic paediatric population is greater than that reported in the
      symptomatic adult population, whereas the prevalence of intra-testicular
      macrocalcification is lower. It is speculated that TM and macrocalcification
      represent different pathways for the possible risk of testicular tumour
      development.

PMID- 22464922
TI  - Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS
      project: prospective follow-up of 245 clinical high-risk outpatients in four
      countries.
AB  - BACKGROUND: In selected samples, a considerable number of patients at clinical
      high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical
      psychiatric disorders. It is not known how clinical diagnoses correspond to or
      even predict transitions to psychosis (TTP). Our aim was to examine distributions
      of life-time and current Axis I diagnoses, and their association with TTP in CHR
      patients. METHODS: In the EPOS (European Prediction of Psychosis Study) project,
      six European outpatient centres in four countries examined 245 young help-seeking
      patients, who fulfilled the inclusion criteria for clinical risk of psychosis
      according to the Structured Interview for Prodromal Syndromes (SIPS 3.0) or the
      Bonn Scale for the Assessment of Basic Symptoms - Prediction List basic symptoms
      (BASBS-P). Patients who had experienced a psychotic episode lasting more than one
      week were excluded. Baseline and life-time diagnoses were assessed by the
      Structured Clinical Interview for DSM-IV (SCID-I). TTP was defined by
      continuation of BLIPS for more than seven days and predicted in Cox-regression
      analysis. RESULTS: Altogether, 71% of the CHR patients had one or more life-time
      and 62% one or more current SCID-I diagnosis; about a half in each category
      received a diagnosis of life-time depressive and anxiety disorder. Currently, 34%
      suffered from depressive and 39% from anxiety disorder. Four percent received a
      current SCID diagnosis of bipolar, and 6.5% of somatoform disorder. During follow
      up, 37 (15.1%) patients had developed full-blown psychosis. In bivariate
      analyses, current non-psychotic bipolar disorder associated significantly with
      TTP. In multivariate analyses, current bipolar disorder, somatoform and unipolar
      depressive disorders associated positively, and anxiety disorders negatively,
      with TTP. CONCLUSIONS: Both life-time and current mood and anxiety disorders are
      highly prevalent among clinical help-seeking CHR patients and need to be
      carefully evaluated. Among CHR patients, occurrence of bipolar, somatoform and
      depressive disorders seems to predict TTP, while occurrence of anxiety disorder
      may predict non-transition to psychosis.

PMID- 22464923
TI  - Robust colour calibration of an imaging system using a colour space transform and
      advanced regression modelling.
AB  - A new algorithm for the conversion of device dependent RGB colour data into
      device independent L*a*b* colour data without introducing noticeable error has
      been developed. By combining a linear colour space transform and advanced
      multiple regression methodologies it was possible to predict L*a*b* colour data
      with less than 2.2 colour units of error (CIE 1976). By transforming the red,
      green and blue colour components into new variables that better reflect the
      structure of the L*a*b* colour space, a low colour calibration error was
      immediately achieved (DeltaE(CAL) = 14.1). Application of a range of regression
      models on the data further reduced the colour calibration error substantially
      (multilinear regression DeltaE(CAL) = 5.4; response surface DeltaE(CAL) = 2.9;
      PLSR DeltaE(CAL) = 2.6; LASSO regression DeltaE(CAL) = 2.1). Only the PLSR models
      deteriorated substantially under cross validation. The algorithm is adaptable and
      can be easily recalibrated to any working computer vision system. The algorithm
      was tested on a typical working laboratory computer vision system and delivered
      only a very marginal loss of colour information DeltaE(CAL) = 2.35. Colour
      features derived on this system were able to safely discriminate between three
      classes of ham with 100% correct classification whereas colour features measured
      on a conventional colourimeter were not.

PMID- 22464924
TI  - Meat quality characteristics of lambs of three organically raised breeds.
AB  - Carcass and meat (muscullus quadriceps femoris [MQF]) quality characteristics
      were evaluated in ten lambs per each of Zwartbles (ZW), Suffolk (SF) and Oxford
      Down (OD) breeds, raised organically and slaughtered at a mean live weight of 38
      kg. Meat of ZW lambs had lower (P<0.05) collagen, myoglobin and intramuscular fat
      content than OD lambs, and lower (P<0.05) tenderness and juiciness scores in
      comparison with OD and SF lambs. Despite a low polyunsaturated/saturated fatty
      acid ratio (0.13 in all three breeds; P>0.05), meat of the pasture-fattened lambs
      can be considered a dietetically superior food with very favourable (0.85-0.88;
      P>0.05) polyunsaturated fatty acid n - 6/n - 3 ratio, and containing per 100g of
      muscle on average 62 mg of EPA+DHA (differences between breeds not significant,
      P>0.05) and no more than 20mg of dietetically unfavourable arachidonic acid.

PMID- 22464925
TI  - Highly sensitive detection of alkaline phosphatase using molecular beacon probes
      based on enzymatic polymerization.
AB  - We have developed a new methodology for highly sensitive alkaline phosphatase
      assay using molecular beacon probes. No incubation step is needed to obtain a
      limit of detection for ALP of 2*10(-16) M. Furthermore, ALP inhibition by the
      inhibitor okadaic acid is shown, demonstrating the potential for high-throughput
      screening for inhibitors.

PMID- 22464926
TI  - Evaluation of Pseudomonas aeruginosa (PAO1) adhesion to human alveolar epithelial
      cells A549 using SYTO 9 dye.
AB  - Pseudomonas aeruginosa is an aerobic Gram-negative bacterium characterized by a
      natural resistance to several antibiotics. It is a major cause of nosocomial
      infections in patients with compromised host defence mechanisms mainly related to
      the respiratory tract. P. aeruginosa infection first step is the adhesion of the
      bacteria to the host cells and thus, the development of techniques that can
      easily assess adhesion of bacteria strains and of bacteria isolated from
      biological samples is fundamental. The aim of our work was to develop a fast and
      effective method to evaluate the adhesion of P. aeruginosa to bronchial
      epithelial cells. To meet our goal we optimized a staining protocol using the
      vital dye SYTO 9 and P. aeruginosa PAO1. We established the appropriate dying
      conditions as well as the stability of the stained bacteria. Adhesion was first
      measured using the traditional plate counting method and then, adhesion values
      were compared to those obtained using a fluorescence microplate reader and
      epifluorescence microscopy. Our results show that the use of SYTO 9 does not
      interfere with the bacteria viability, bacteria cell growth, and adhesion of P.
      aeruginosa to A549 epithelial cells. Both the fluorescence microplate reader and
      the epifluorescence microscopy gave similar results to those attained with the
      plate counting method, however, the epifluorescence microscopy also allowed for
      simultaneous discrimination of damaging effects on the human cells. Overall, our
      data indicate that the use of SYTO 9 combined with a fluorescence microplate
      reader or an epifluorescence microscope provides a rapid method to evaluate the
      adhesion of P. aeruginosa to human epithelial cells. However, to show
      unequivocally that a specific drug or compound has a truly inhibitory effect on
      the bacterial adhesion without affecting the number of human cells, the
      epifluorescence microscopy is recommended.

PMID- 22464927
TI  - Bioelectrical impedance analysis and skinfold thickness sum in assessing body fat
      mass of renal dialysis patients.
AB  - OBJECTIVE: In chronic renal failure patients under hemodialysis (HD) treatment,
      the availability of simple, safe, and effective tools to assess body composition
      enables evaluation of body composition accurately, in spite of changes in body
      fluids that occur in dialysis therapy, thus contributing to planning and
      monitoring of nutritional treatment. We evaluated the performance of
      bioelectrical impedance analysis (BIA) and the skinfold thickness sum (SKF) to
      assess fat mass (FM) in chronic renal failure patients before (BHD) and after
      (AHD) HD, using air displacement plethysmography (ADP) as the standard method.
      DESIGN: This single-center cross-sectional trial involved comparing the FM of 60
      HD patients estimated BHD and AHD by BIA (multifrequential; 29 women, 31 men) and
      by SKF with those estimated by the reference method, ADP. Body fat-free mass
      (FFM) was also obtained by subtracting the total body fat from the individual
      total weight. RESULTS: Mean estimated FM (kg [%]) observed by ADP BHD was 17.95
      +/- 0.99 kg (30.11% +/- 1.30%), with a 95% confidence interval (CI) of 16.00 to
      19.90 (27.56 to 32.66); mean estimated FM observed AHD was 17.92 +/- 1.11 kg
      (30.04% +/- 1.40%), with a 95% CI of 15.74 to 20.10 (27.28 to 32.79). Neither
      study period showed a difference in FM and FFM (for both kg and %) estimates by
      the SKF method when compared with ADP; however, the BIA underestimated the FM and
      overestimated the FFM (for both kg and %) when compared with ADP. CONCLUSION: The
      SKF, but not the BIA, method showed results similar to ADP and can be considered
      adequate for FM evaluation in HD patients.

PMID- 22464928
TI  - Radiolabeling of DOTATOC with the long-lived positron emitter 44Sc.
AB  - The positron-emitting radionuclide (44)Sc with a half-life of 3.97 h and a
      beta(+) branching of 94.3% is of potential interest for clinical PET. As so far
      it is available from a (44)Ti/(44)Sc generator in Mainz, where long-lived (44)Ti
      decays to no-carrier-added (nca) (44)Sc. The (44)Sc is a trivalent metal cation
      and should be suitable for complexation with many well established bifunctional
      chelators conjugated to peptides or other molecular targeting vectors. Thus, the
      aim of this work was to investigate the potential of (44)Sc for labeling of DOTA
      conjugated peptides. DOTA-D-Phe(1)-Tyr(3)-octreotide (DOTATOC) was used as a
      model molecule to study and optimize labeling procedure. Reaction parameters such
      as buffer conditions, concentration of peptide, pH range, reaction temperature
      and time were optimized. Addition of 21 nmol of DOTATOC to (44)Sc in ammonium
      acetate buffer pH 4.0 provided labeling yields >98% within 25 min of heating in
      an oil-bath at 95 degrees C. This time can be reduced to 3 min only by applying
      microwave supported heating. (44)Sc-DOTATOC was found to be stable in 0.9% NaCl,
      PBS pH 7.4, fetal calf and human serums, and also in the presence of competing
      metal cations (Fe(3+), Ca(2+), Cu(2+), Mg(2+)), as well as other ligand
      competitors, like EDTA and DTPA, even after almost 25 h incubation at 37 degrees
      C. Present study shows that nca (44)Sc forms stable complexes with the
      macrocyclic ligand DOTA and that (44)Sc-DOTATOC and analog targeting vectors may
      be synthesized for further preclinical and clinical investigations.

PMID- 22464929
TI  - Influence of the thorium decay series on the background of high-resolution gamma
      ray spectrometers.
AB  - The background induced by the members of the thorium decay sequence in six high
      resolution, gamma-ray spectrometers was analyzed. For the analysis, the count
      rates in the peaks of the background spectra, normalized to the unit of emission
      probability and detection probability, were used. The energy dependence of these
      normalized count rates carries information about the location of the sources of
      contamination. The contributions of the detector contamination, the contamination
      of the shielding material and the radiation penetrating the shield were
      calculated. The comparison of these contributions among the spectrometers pointed
      to the weaknesses of some shields, making such a comparison a useful tool for
      assessing the effectiveness of the shields.

PMID- 22464930
TI  - Performance test for radon measuring instruments using radon chamber at PTB.
AB  - An intercomparison on radon ((222)Rn) measuring instruments was carried out at
      the Physikalisch Technische Bundesanstalt, Germany (PTB). Two types of alpha
      track detectors based on a passive (222)Rn-thoron ((220)Rn) discriminative
      measurement technique were used: these were the commercially available Raduet and
      Radopot detectors that were developed and calibrated by the National Institute of
      Radiological Sciences, Japan (NIRS). The (222)Rn grab sampling and continuous
      measurement methods were also compared using the PTB pulse ionization chamber.
      The results using the passive detectors showed that there was a good agreement
      between the time-integrated (222)Rn concentrations obtained from the Raduet
      detectors and the PTB pulse ionization chamber, as in the case with the Radopot
      detectors. In the grab sampling measurements, the agreement between the (222)Rn
      concentrations measured using the NIRS gas storage ionization chamber and the PTB
      pulse ionization chamber was within 5% as in the case with the NIRS scintillation
      cell measurement. Similar to the measurements of the passive detectors and grab
      sampling, little distinct difference in the (222)Rn concentration was observed
      for the NIRS continuous electrostatic collection monitor.

PMID- 22464931
TI  - Efficiency fitting for TDCR measurement data using polynomial approximation and
      the Newton-Raphson method.
AB  - A tritium radioactivity source was measured by triple-to-double coincidence ratio
      (TDCR) equipment of the National Metrology Institute of Japan (NMIJ), and
      measured data were fitted using polynomial approximation and the Newton-Raphson
      method, a technique whereby equations are solved numerically by successive
      approximations. The method used to obtain the activity minimizes the difference
      between statistically calculated data and experimental data. In the fitting,
      since calculated statistical efficiency and TDCR values are discrete, the
      calculated efficiencies are approximated by quadratic functions around
      experimental values and the Newton-Raphson method is used for convergence at the
      minimal difference between experimental data and calculated data. In this way,
      the activity of tritium was successfully obtained.

PMID- 22464932
TI  - Effects of manual threshold setting on image analysis results of a sandstone
      sample structural characterization by X-ray microtomography.
AB  - Binarization process plays an important role in structural characterization by
      means of micro-CT images analysis. The choice of the correct threshold to
      separate porous phase from the material is the procedure for binary images
      creation. Slight variations of the threshold level led to substantial variations
      in physical parameters determination. The aim of this work is to evaluate these
      variations based on manual threshold settings data of five operators. Porosity
      and pore size distribution of a sandstone sample were determined.

PMID- 22464933
TI  - Study the effect of beryllium reflector poisoning on the Syrian MNSR.
AB  - Neutron interactions with beryllium lead to formation of (3)H and strong neutron
      absorbers (3)He and (6)Li in the reflector (so called beryllium poisoning). After
      the reactor shutdown, the concentration of (3)He increases in time due to tritium
      decay. This paper illustrates the impact of poisoning accumulation in the
      beryllium reflectors on reactivity for the Syrian MNSR research reactor. The
      prediction of (6)Li and (3)He poison concentrations, initiated by the
      9Be(n,alpha) reaction, in the beryllium reflectors of the MNSR was also
      presented. The results were based on MCNP Monte Carlo calculations and solutions
      to the differential equations which describe the time dependent poison
      concentrations as a function of reactor operation time and shutdown periods. The
      whole reactor history was taken into account to predict reliable values of
      parasitic isotope concentrations. It was found that the (3)He and (6)Li
      accumulations in the beryllium reflectors during the actual working history
      decreased the excess reactivity by about 28%. While, the effect became more
      significant at the reactor life's end and the reactor became subcritical after
      25,000 h operation. The results contained in this paper could be used in assess
      the safety analysis of the MNSR reactor.

PMID- 22464934
TI  - Comparison of attitudes about polio, polio immunization, and barriers to polio
      eradication between primary health center physicians and private pediatricians in
      India.
AB  - OBJECTIVES: The objectives of this study were to compare attitudes and
      perceptions of primary health center (PHC) physicians and pediatricians in Uttar
      Pradesh and Bihar toward polio disease, immunization, and eradication, and to
      identify barriers to polio eradication. METHODS: PHC physicians from blocks with
      at least one confirmed polio case during January 2006 to June 2009 were selected
      for an in-person survey. Pediatricians were members of the Indian Academy of
      Pediatrics and were selected from a national directory of members for telephone
      or mail survey. RESULTS: A higher percentage of PHC physicians than pediatricians
      reported that an unvaccinated child was susceptible to polio (82.1% vs. 63.0%,
      p<0.0001) and that polio disease was severe in a child aged 1-5 years (77.7% vs.
      62.2%, p<0.0001). PHC physicians and pediatricians expressed confidence in the
      protectiveness and safety of oral polio vaccine and cited parents' lack of
      awareness of the importance of polio eradication as an important barrier to
      eradication. Strengthening routine immunization efforts was reported as the
      leading intervention required to eradicate polio. CONCLUSIONS: PHC physicians and
      pediatricians support and have confidence in the success of polio eradication
      efforts. These findings will be useful for policy-makers involved in the planning
      of eradication strategies. Providers and parents need to maintain confidence in
      polio vaccination if polio is to be eradicated.

PMID- 22464935
TI  - The impact of the CACNA1C risk allele on limbic structures and facial emotions
      recognition in bipolar disorder subjects and healthy controls.
AB  - INTRODUCTION: Impairments in facial emotion recognition (FER) have been reported
      in bipolar disorder (BD) during all mood states. FER has been the focus of
      functional magnetic resonance imaging studies evaluating differential activation
      of limbic regions. Recently, the alpha1-C subunit of the L-type voltage-gated
      calcium channel (CACNA1C) gene has been described as a risk gene for BD and its
      Met allele found to increase CACNA1C mRNA expression. In healthy controls, the
      CACNA1C risk (Met) allele has been reported to increase limbic system activation
      during emotional stimuli and also to impact on cognitive function. The aim of
      this study was to investigate the impact of CACNA1C genotype on FER scores and
      limbic system morphology in subjects with BD and healthy controls. MATERIAL AND
      METHODS: Thirty-nine euthymic BD I subjects and 40 healthy controls were
      submitted to a FER recognition test battery and genotyped for CACNA1C. Subjects
      were also examined with a 3D 3-Tesla structural imaging protocol. RESULTS: The
      CACNA1C risk allele for BD was associated to FER impairment in BD, while in
      controls nothing was observed. The CACNA1C genotype did not impact on amygdala or
      hippocampus volume neither in BD nor controls. LIMITATIONS: Sample size.
      CONCLUSION: The present findings suggest that a polymorphism in calcium channels
      interferes FER phenotype exclusively in BD and doesn't interfere on limbic
      structures morphology.

PMID- 22464936
TI  - Interacting with nature improves cognition and affect for individuals with
      depression.
AB  - BACKGROUND: This study aimed to explore whether walking in nature may be
      beneficial for individuals with major depressive disorder (MDD). Healthy adults
      demonstrate significant cognitive gains after nature walks, but it was unclear
      whether those same benefits would be achieved in a depressed sample as walking
      alone in nature might induce rumination, thereby worsening memory and mood.
      METHODS: Twenty individuals diagnosed with MDD participated in this study. At
      baseline, mood and short term memory span were assessed using the PANAS and the
      backwards digit span (BDS) task, respectively. Participants were then asked to
      think about an unresolved negative autobiographical event to prime rumination,
      prior to taking a 50-min walk in either a natural or urban setting. After the
      walk, mood and short-term memory span were reassessed. The following week,
      participants returned to the lab and repeated the entire procedure, but walked in
      the location not visited in the first session (i.e., a counterbalanced within
      subjects design). RESULTS: Participants exhibited significant increases in memory
      span after the nature walk relative to the urban walk, p<.001, eta(p)(2)=.53 (a
      large effect-size). Participants also showed increases in mood, but the mood
      effects did not correlate with the memory effects, suggesting separable
      mechanisms and replicating previous work. LIMITATIONS: Sample size and
      participants' motivation. CONCLUSIONS: These findings extend earlier work
      demonstrating the cognitive and affective benefits of interacting with nature to
      individuals with MDD. Therefore, interacting with nature may be useful clinically
      as a supplement to existing treatments for MDD.

PMID- 22464937
TI  - Pediatric bipolar disorder and ADHD: family history comparison in the LAMS
      clinical sample.
AB  - BACKGROUND: Transgenerational association of bipolar spectrum disorder (BPSD) and
      attention deficit/hyperactivity disorder (ADHD) has been reported, but
      inconclusively. METHOD: Children ages 6-12 were systematically recruited at first
      outpatient visit at 9 clinics at four universities and reliably diagnosed; 621
      had elevated symptoms of mania (>12 on the Parent General Behavior Inventory 10
      Item Mania Scale); 86 had scores below 12. We analyzed baseline data to test a
      familial association hypothesis: compared to children with neither BPSD nor ADHD,
      those with either BPSD or ADHD would have parents with higher rates of both
      bipolar and ADHD symptoms, and parents of comorbid children would have even
      higher rates of both. RESULTS: Of 707 children, 421 had ADHD without BPSD, 45
      BPSD without ADHD, 117 comorbid ADHD+BPSD, and 124 neither. The rate of parental
      manic symptoms was similar for the comorbid and BPSD-alone groups, significantly
      greater than for ADHD alone and "neither" groups, which had similar rates. ADHD
      symptoms in parents of children with BPSD alone were significantly less frequent
      than in parents of children with ADHD (alone or comorbid), and no greater than
      for children with neither diagnosis. Family history of manic symptoms, but not
      ADHD symptoms, was associated with parent-rated child manic-symptom severity over
      and above child diagnosis. LIMITATIONS: The sample was not epidemiologic, parent
      symptoms were based on family history questions, and alpha was 0.05 despite
      multiple tests. CONCLUSIONS: These results do not support familial linkage of
      BPSD and ADHD; they are compatible with heritability of each disorder separately
      with coincidental overlap.

PMID- 22464938
TI  - The 1st International standard for transforming growth factor-beta3 (TGF-beta3).
AB  - One candidate preparation of human sequence recombinant transforming growth
      factor-beta3 (TGF-beta3) was formulated and lyophilized at NIBSC prior to
      evaluation in a collaborative study for its suitability to serve as an
      international standard. The preparation was tested by 8 laboratories using in
      vitro bioassays and immunoassays. The candidate preparation 09/234 was judged
      suitable to serve as an international standard based on the data obtained for
      biological activity and stability. On the basis of the results reported here, the
      preparation coded 09/234 was established by the WHO Expert Committee on
      Biological Standardisation (ECBS) as the WHO 1st IS for human TGF-beta3 with an
      assigned value for TGF-beta3 activity of 19,000 IU/ampoule.

PMID- 22464939
TI  - A numerical parametric study of the mechanical action of pulsatile blood flow
      onto axisymmetric stenosed arteries.
AB  - In the present paper, a fluid-structure interaction model is developed,
      questioning how the mechanical action of the blood onto an atheromatous plaque is
      affected by the length and the severity of the stenosis. An axisymmetric model is
      considered. The fluid is assumed Newtonian. The plaque is modelled as a
      heterogeneous hyperelastic anisotropic solid composed of the arterial wall, the
      lipid core and the fibrous cap. Transient velocity and pressure conditions of
      actual pulsatile blood flow are prescribed. The simulation is achieved using the
      Arbitrary Lagrangian Eulerian scheme in the COMSOL commercial Finite Element
      package. The results reveal different types of behavior in function of the length
      (denoted L) and severity (denoted S) of the stenosis. Whereas large plaques (L>10
      mm) are mostly deformed under the action of the blood pressure, it appears that
      shorter plaques (L<10 mm) are significantly affected by the shear stresses. The
      shear stresses tend to deform the plaque by pinching it. This effect is called:
      "the pinching effect". It has an essential influence on the mechanical response
      of the plaque. For two plaques having the same radius severity S=45%, the maximum
      stress in the fibrous cap is 50% larger for the short plaque (L=5 mm) than for a
      larger plaque (L=10 mm), and the maximum wall shear stress is increased by 100%.
      Provided that they are confirmed by experimental investigations, these results
      may offer some new perspectives for understanding the vulnerability of short
      plaques.

PMID- 22464940
TI  - The impact of culture change on elders' behavioral symptoms: a longitudinal
      study.
AB  - OBJECTIVES: Distressing behavioral symptoms often associated with dementia are
      not uncommon in the long term care setting. Culture change with its "person
      centered approach to care" provides a potential nonpharmacological intervention
      to reduce these symptoms. The purpose of this study was to examine the
      relationship between a culture change initiative and nursing home elders'
      behavioral symptoms. DESIGN: Seven long term care communities (nursing units in 3
      skilled nursing facilities) participated in a culture change intervention
      designed to transform the nursing home experience from a traditional hospital
      model of care to one that is person-centered. Six comparison communities were
      matched to the intervention communities and continued to function along the
      typical nursing home organizational structure. Data were collected at baseline
      and 2 years later. METHODS: Subjects were 101 elders (intervention group n = 50,
      comparison group n = 51). Each elder's primary day certified nursing assistant
      completed the Cohen-Mansfield Agitation Inventory, examining frequency of
      behavioral symptoms, including verbal and physical agitation as well as more
      forceful behaviors (eg, hitting, kicking) at both data collection periods.
      RESULTS: After controlling for functional status and race, a significant
      condition by time interaction was found for physical agitation and forceful
      behaviors with the person-centered group maintaining levels of behavioral
      symptoms as compared with a significant increase over time among the comparison
      group. A trend with the same pattern was found for verbal agitation. CONCLUSIONS:
      Person-centered care demonstrated potential as a nonpharmacological intervention
      for distressing behavioral symptoms. The positive impact of culture change
      appears to extend to elders with cognitive impairment who are less obvious
      beneficiaries of this model, featuring the central principals of autonomy and
      person-centered care.

PMID- 22464941
TI  - Clinical features of obsessive-compulsive disorder with hoarding symptoms: a
      multicenter study.
AB  - BACKGROUND: Factor analyses indicate that hoarding symptoms constitute a
      distinctive dimension of obsessive-compulsive disorder (OCD), usually associated
      with higher severity and limited insight. The aim was to compare demographic and
      clinical features of OCD patients with and without hoarding symptoms. METHOD: A
      cross sectional study was conducted with 1001 DSM-IV OCD patients from the
      Brazilian Research Consortium of Obsessive-Compulsive Spectrum Disorders (CTOC),
      using several instruments. The presence and severity of hoarding symptoms were
      determined using the Dimensional Yale-Brown Obsessive-Compulsive Scale.
      Statistical univariate analyses comparing factors possibly associated with
      hoarding symptoms were conducted, followed by logistic regression to adjust the
      results for possible confounders. RESULTS: Approximately half of the sample
      (52.7%, n = 528) presented hoarding symptoms, but only four patients presented
      solely the hoarding dimension. Hoarding was the least severe dimension in the
      total sample (mean score: 3.89). The most common lifetime hoarding symptom was
      the obsessive thought of needing to collect and keep things for the future
      (44.0%, n = 440). After logistic regression, the following variables remained
      independently associated with hoarding symptoms: being older, living alone,
      earlier age of symptoms onset, insidious onset of obsessions, higher anxiety
      scores, poorer insight and higher frequency of the symmetry-ordering symptom
      dimension. Concerning comorbidities, major depressive, posttraumatic stress and
      attention deficit/hyperactivity disorders, compulsive buying and tic disorders
      remained associated with the hoarding dimension. CONCLUSION: OCD hoarding
      patients are more likely to present certain clinical features, but further
      studies are needed to determine whether OCD patients with hoarding symptoms
      constitute an etiologically discrete subgroup.

PMID- 22464942
TI  - The burden of full and subsyndromal posttraumatic stress disorder among police
      involved in the World Trade Center rescue and recovery effort.
AB  - BACKGROUND: This study examined the prevalence, correlates, and perceived mental
      healthcare needs associated with subsyndromal PTSD in police involved in the
      World Trade Center (WTC) rescue and recovery effort. METHODS: A total of 8466
      police completed an interview/survey as part of the WTC Medical monitoring and
      Treatment Program an average of four years after 9/11/2001. RESULTS: The past
      month prevalence of full and subsyndromal WTC-related PTSD was 5.4% and 15.4%,
      respectively. Loss of someone or knowing someone injured on 9/11 (odds ratios
      [ORs]=1.56-1.86), pre-9/11 stressors (ORs=1.30-1.50), family support (ORs=0.83
      0.94), and union membership (ORs=0.50-0.52) were associated with both full and
      subsyndromal PTSD. Exposure to the dust cloud (OR=1.36), performing search and
      rescue work (OR=1.29), and work support (OR=0.89) were additionally associated
      with subsyndromal PTSD. Rates of comorbid depression, panic disorder, and alcohol
      use problems (ORs=3.82-41.74), and somatic symptoms and functional difficulties
      (ORs=1.30-1.95) were highest among police with full PTSD, with intermediate rates
      among police with subsyndromal PTSD (ORs=2.93-7.02; and ORs=1.18-1.60,
      respectively). Police with full and subsyndromal PTSD were significantly more
      likely than controls to report needing mental healthcare (41.1% and 19.8%,
      respectively, versus 6.8% in trauma controls). CONCLUSIONS: These results
      underscore the importance of a more inclusive and dimensional conceptualization
      of PTSD, particularly in professions such as police, as operational definitions
      and conventional screening cut-points may underestimate the psychological burden
      for this population. Accordingly, psychiatric clinicians should assess for
      disaster-related subsyndromal PTSD symptoms in disaster response personnel.

PMID- 22464944
TI  - Life stressors, emotional distress, and trauma-related thoughts occurring in the
      24 h preceding active duty U.S. soldiers' suicide attempts.
AB  - External life events and internal experiences (i.e., emotional distress and
      trauma-related thoughts) occurring in the 24 h preceding suicide attempts were
      examined in a sample of active duty U.S. soldiers. Seventy-two Soldiers (66 male,
      6 female; 65.3% Caucasian, 9.7% African-American, 2.8% Asian, 2.8% Pacific
      Islander, 4.2% Native American, and 9.7% "other"; age M = 27.34, SD = 6.50) were
      interviewed using the suicide attempt self injury interview to assess the
      occurrence of external events and internal experiences on the day of their
      suicide attempts, and to determine their associations with several dimensions of
      suicide risk: suicidal intent, lethality, and deliberation about attempting.
      Multiple external stressors and internal states were experienced by soldiers in
      the 24 h preceding their suicide attempts, with emotional distress being the most
      common. Trauma-related thoughts were much less frequently reported in the 24 h
      preceding suicide attempts. Emotional experiences were directly associated with
      suicidal intent, and explained the relationship between external events and
      suicidal intent. Lethality was unrelated to any external events, emotional
      experiences, or trauma-related thoughts. Greater emotional distress and trauma
      related thoughts were associated with shorter deliberation about whether or not
      to attempt suicide. Soldiers experience multiple sources of distress in the
      period immediately preceding their suicide attempts. Soldiers who experience more
      negative emotional experiences have a stronger desire for suicide and spend less
      time deliberating before an attempt.

PMID- 22464945
TI  - Better compounds faster: the development and exploitation of a desktop predictive
      chemistry toolkit.
AB  - Today's drug designer has access to vast quantities of data and an impressive
      array of sophisticated computational methods. At the same time, there is
      increasing pressure on the pharmaceutical industry to improve its productivity
      and reduce candidate drug attrition. We set out to develop a highly integrated
      suite of design and data analysis tools underpinned by the best predictive
      chemistry methods and models, with the aim of enabling multi-disciplinary
      compound design teams to make better informed design decisions. In this article
      we address the challenges of developing a powerful, flexible and user-friendly
      toolkit, and of maximising its exploitation by the design community. We describe
      the impact the toolkit has had on drug discovery projects and give our
      perspective on the future direction of this activity.

PMID- 22464943
TI  - Differential relationships of impulsivity or antisocial symptoms on P50, N100, or
      P200 auditory sensory gating in controls and antisocial personality disorder.
AB  - Limited information is available on the relationship between antisocial
      personality disorder (ASPD) and early filtering, or gating, of information, even
      though this could contribute to the repeatedly reported impairment in ASPD of
      higher-order information processing. In order to investigate early filtering in
      ASPD, we compared electrophysiological measures of auditory sensory gating
      assessed by the paired-click paradigm in males with ASPD (n = 37) to healthy
      controls (n = 28). Stimulus encoding was measured by P50, N100, and P200 auditory
      evoked potentials; auditory sensory gating (ASG) was measured by a reduction in
      amplitude of evoked potentials following click repetition. Effects were studied
      of co-existing past alcohol or drug use disorders, ASPD symptom counts, and trait
      impulsivity. Controls and ASPD did not differ in P50, N100, or P200 amplitude or
      ASG. Past alcohol or drug use disorders had no effect. In controls, impulsivity
      related to improved P50 and P200 gating. In ASPD, P50 or N100 gating was impaired
      with more symptoms or increased impulsivity, respectively, suggesting impaired
      early filtering of irrelevant information. In controls the relationship between
      P50 and P200 gating and impulsivity was reversed, suggesting better gating with
      higher impulsivity scores. This could reflect different roles of ASG in
      behavioral regulation in controls versus ASPD.

PMID- 22464946
TI  - Biologics: the next generation of analgesic drugs?
AB  - For many decades, there have been few novel therapies for pain, and the number of
      promising targets that have been genuinely validated in the clinic is small.
      Discovery and development of biologic therapies for analgesia provides a better
      opportunity to test such targets, potentially providing new and effective
      therapies. Biologics have revolutionised the treatment of many diseases, with the
      greatest advances seen in oncology and inflammatory disorders. Across a broad
      spectrum of severe, chronic pain disorders - including inflammatory pain,
      neuropathic pain and cancer pain - biologics could offer patients safer and more
      effective alternatives to currently available treatments. As such, progression of
      large-molecule therapies is becoming a strategic priority for companies as they
      look to advance their portfolios.

PMID- 22464948
TI  - Animal models of working memory: a review of tasks that might be used in
      screening drug treatments for the memory impairments found in schizophrenia.
AB  - The Cognitive Neuroscience Treatment Research to Improve Cognition in
      Schizophrenia (CNTRICS) meeting on "Selecting Promising Animal Paradigms" focused
      on a consideration of valid tasks for drug discovery in non-humans. This
      consensus review is based on a break-out session with experts from academia and
      industry which considered tasks that tap working memory in animals. The specific
      focus of the session was on tasks measuring goal maintenance, memory capacity,
      and interference control. Of the tasks nominated for goal maintenance, the most
      developed paradigms were operant delayed-non-matching-to-position tasks, and
      touch-screen variants of these may hold particular promise. For memory capacity,
      the task recommended for further development was the span task, although it is
      recognized that more work on its neural substrates is required. For interference
      control, versions of the n-back task were felt to resemble the deficits found in
      schizophrenia, although additional development of these tasks is also required. 

PMID- 22464949
TI  - Antenatal group care in a midwifery group practice--a midwife' perspective.
AB  - The following article describes a midwife's experience in the adaption of the
      CenteringPregnancy model into her own group practice to provide education and
      support to the women in her care. Using personal experience and feedback from
      women and midwifery students the author describes not only the process of group
      care in her work context but the apparent benefits to women, families', midwifery
      students and herself. Antenatal group care was so successful for the author that
      it extended to postnatal group care and student group care, all well attended and
      sought after groups. This is an exciting and innovative way to provide care for
      women and families and the author encourages other midwives and group practices
      to consider how they can adapt and progress similar group care into their own
      practice.

PMID- 22464947
TI  - MT1-MMP-dependent remodeling of cardiac extracellular matrix structure and
      function following myocardial infarction.
AB  - The myocardial extracellular matrix (ECM), an interwoven meshwork of proteins,
      glycoproteins, proteoglycans, and glycosaminoglycans that is dominated by
      polymeric fibrils of type I collagen, serves as the mechanical scaffold on which
      myocytes are arrayed for coordinated and synergistic force transduction.
      Following ischemic injury, cardiac ECM remodeling is initiated via localized
      proteolysis, the bulk of which has been assigned to matrix metalloproteinase
      (MMP) family members. Nevertheless, the key effector(s) of myocardial type I
      collagenolysis both in vitro and in vivo have remained unidentified. In this
      study, using cardiac explants from mice deficient in each of the major type I
      collagenolytic MMPs, including MMP-13, MMP-8, MMP-2, MMP-9, or MT1-MMP, we
      identify the membrane-anchored MMP, MT1-MMP, as the dominant collagenase that is
      operative within myocardial tissues in vitro. Extending these observations to an
      in vivo setting, mice heterozygous for an MT1-MMP-null allele display a distinct
      survival advantage and retain myocardial function relative to wild-type
      littermates in an experimental model of myocardial infarction, effects associated
      with preservation of the myocardial type I collagen network as a consequence of
      the decreased collagenolytic potential of cardiac fibroblasts. This study
      identifies MT1-MMP as a key MMP responsible for effecting postinfarction cardiac
      ECM remodeling and cardiac dysfunction.

PMID- 22464950
TI  - Impact of the per-operatory application of GLIADEL wafers (BCNU, carmustine) in
      combination with temozolomide and radiotherapy in patients with glioblastoma
      multiforme: efficacy and toxicity.
AB  - PURPOSE: For the last few years wafers of Gliadel have been inserted into the
      operation cavity in patients with glioblastoma multiforme. This is followed by
      concurrent radio-chemotherapy with temozolomide (TMZ) according to the Stupp
      protocol. Only a few studies have investigated this kind of treatment regimen and
      the impact in terms of survival and toxicity of the combination of Gliadel with
      TMZ and radiotherapy. METHODS AND MATERIALS: From November 2006 to January 2010,
      24 patients with a newly diagnosed glioblastoma have undergone a tumour resection
      which was considered to be macroscopically complete in 12 cases and with tumour
      residue in another 12 cases. The mean age at the moment of diagnosis was
      60.25years and the median age 63. Twenty-three patients underwent subsequently
      concurrent radio-chemotherapy with TMZ followed by cycles of elevated doses of
      TMZ as an adjuvant treatment. One patient had adjuvant radiotherapy alone
      followed by adjuvant chemotherapy. Thirteen were able to receive 6 or more cycles
      of adjuvant TMZ. Seven patients had received less than 6 cycles of TMZ as an
      adjuvant therapy. Two patients did not receive adjuvant TMZ at all. RESULTS: The
      median overall survival of our group was 19.2months and the median progression
      free survival was 12.3months. Overall survival for the macroscopically complete
      resection patients was 14months, and 12.85months in subtotal-resection patients.
      The median OS was 14.25months for patients PS 0 - 1 at the moment of diagnosis
      and 12.65 for PS 2 patients. Chemotherapy with TMZ had to be stopped prematurely
      in 10 cases due to haematotoxicity, digestive toxicity or early relapse.
      CONCLUSIONS: The concomitant use of surgery with implantation of BCNU wafers and
      radio-chemotherapy seems to be well tolerated. Despite the small number of
      patients treated in our group, particular attention should be paid to the
      potential haematological consequences of this multimodal treatment regimen.

PMID- 22464951
TI  - Test-retest reliability of 3D ultrasound measurements of the thoracic spine.
AB  - OBJECTIVE: To explore the reliability of the Zebris CMS 20 ultrasound analysis
      system with pointer application for measuring end-range flexion, end-range
      extension, and neutral kyphosis angle of the thoracic spine. SETTING: The study
      was performed within the School of Physiotherapy in cooperation with the
      Orthopedic Department at a University Hospital. PARTICIPANTS: The thoracic spines
      of 28 healthy subjects were measured. METHODS: Measurements for neutral kyphosis
      angle, end-range flexion, and end-range extension were taken once at each time
      point. The bone landmarks were palpated by one examiner and marked with a pointer
      containing 2 transmitters using a frequency of 40 kHz. A third transmitter was
      fixed to the pelvis, and 3 microphones were used as receiver. The real angle was
      calculated by the software. Bland-Altman plots with 95% limits of agreement,
      intraclass correlations (ICC), standard deviations of mean measurements, and
      standard error of measurements were used for statistical analyses. The test
      retest reliability in this study was measured within a 24-hour interval. MAIN
      OUTCOME MEASUREMENTS: Statistical parameters were used to judge reliability.
      RESULTS: The mean kyphosis angle was 44.8 degrees  with a standard deviation of
      17.3 degrees  at the first measurement and a mean of 45.8 degrees  with a
      standard deviation of 16.2 degrees  the following day. The ICC was high at 0.95
      for the neutral kyphosis angle, and the Bland-Altman 95% limits of agreement were
      within clinical acceptable margins. The ICC was 0.71 for end-range flexion and
      0.34 for end-range extension, whereas the Bland-Altman 95% limits of agreement
      were wider than with the static measurement of kyphosis. Compared with static
      measurements, the analysis of motion with 3-dimensional ultrasound showed an
      increased standard deviation for test-retest measurements. CONCLUSIONS: The test
      retest reliability of ultrasound measuring of the neutral kyphosis angle of the
      thoracic spine was demonstrated within 24 hours. Bland-Altman 95% limits of
      agreement and the standard deviation of differences did not appear to be
      clinically acceptable for measuring flexion and extension.

PMID- 22464952
TI  - Transcription factors Sp1 and Sp3 regulate basal transcription of the human IRF-3
      gene.
AB  - Interferon regulatory factor 3 (IRF-3) plays a crucial role in initiation and
      development of the IFN antiviral response. The expression level of human IRF-3 is
      thought to be closely related to antiviral state of cells. However, the
      mechanisms of the transcription regulation of IRF-3 have remained largely
      unknown. We previously reported that transcription factor E2F1 negatively
      regulates the basal transcriptional activity of IRF-3. Here we demonstrate that
      transcription factors Sp1 and Sp3 up-regulate the basal transcriptional activity
      of IRF-3 and increase IRF-3 expression at mRNA level. By transient transfection
      analysis we revealed that mutation of Sp1/NRF-1 binding site resulted in a
      profound reduction of IRF-3 promoter activity. Overexpression of Sp1 and Sp3, but
      not NRF-1, transactivated the IRF-3 promoter activity in reporter gene assays
      while knocking-down of endogenous Sp1 and Sp3 by a shRNA strategy markedly
      inhibited IRF-3 promoter activity. Chromatin immunoprecipitation (ChIP) assays
      showed that Sp1 and Sp3 interact with the IRF-3 promoter in vivo. These results
      suggest that basal expression level of IRF-3 is regulated by transcription
      factors Sp1 and Sp3.

PMID- 22464953
TI  - Animal systems in the development of treatments for Alzheimer's disease:
      challenges, methods, and implications.
AB  - Substantial resources and effort have been invested into the development of
      therapeutic agents for Alzheimer's disease (AD) with mixed and limited success.
      Research into the etiology of AD with animal models mimicking aspects of the
      disorder has substantially contributed to the advancement of potential therapies.
      Although these models have shown utility in testing novel therapeutic candidates,
      large variability still exists in terms of methodology and how the models are
      utilized. No model has yet predicted a successful disease-modifying therapy for
      AD. This report reviews several of the widely accepted transgenic and
      nontransgenic animal models of AD, highlighting the pathological and behavioral
      characteristics of each. Methodological considerations for conducting preclinical
      animal research are discussed, such as which behavioral tasks and histological
      markers may be associated with the greatest insight into therapeutic benefit. An
      overview of previous and current therapeutic interventions being investigated in
      AD models is presented, with an emphasis on factors that may have contributed to
      failure in past clinical trials. Finally, we propose a multitiered approach for
      investigating candidate therapies for AD that may reduce the likelihood of
      inappropriate conclusions from models and failed trials in humans.

PMID- 22464954
TI  - Therapeutic use of recombinant methionyl human leptin.
AB  - Recombinant methionyl human leptin (r-metHuLeptin) was first used as a
      replacement therapy in patients bearing inactivating mutations in the leptin
      gene. In this indication, it was shown since 1999 to be very efficient in
      inducing a dramatic weight loss in rare children and adults with severe obesity
      due to the lack of leptin. These first clinical trials clearly showed that r
      metHuLeptin acted centrally to reduce food intake, inducing loss of fat mass, and
      to correct metabolic alterations, immune and neuroendocrine defects. A few years
      later, r-metHuLeptin was also shown to reverse the metabolic complications
      associated with lipodystrophic syndromes, due to primary defects in fat storage,
      which induce leptin deficiency. The beneficial effects, which could be mediated
      by central and/or peripheral mechanisms, are thought to mainly involve the
      lowering effects of leptin on ectopic lipid storage, in particular in liver and
      muscles, reducing insulin resistance. Interestingly, r-metHuLeptin therapy also
      reversed the hypothalamic-pituitary-gonadal axis dysfunctions associated with
      hypothalamic amenorrhea. However, if r-metHuLeptin treatment has been shown to be
      dramatically efficient in leptin-deficient states, its very limited effect in
      inducing weight loss in common obese patients revealed that, in patients with
      adequate leptin secretion, mechanisms of leptin resistance and leptin tolerance
      prevent r-metHuLeptin from inducing any additional effects. This review will
      present the current data about the effects of r-metHuLeptin therapy in humans,
      and discuss the recent perspectives of this therapy in new indications.

PMID- 22464955
TI  - A novel Kazal-type trypsin inhibitor from the skin secretion of the Central
      American red-eyed leaf frog, Agalychnis callidryas.
AB  - The chemical complexity of the defensive skin secretion of the red-eyed leaf
      frog, (Agalychnis callidryas), has not been elucidated in detail. During a
      systematic study of the skin secretion peptidomes of phyllomedusine frogs, we
      discovered a novel Kazal-type protein with potent trypsin inhibitory activity (Ki
      = 1.9 nM) that displays the highest degree of structural similarity with Kazal
      proteins from bony fishes. The protein was located in reverse-phase HPLC
      fractions following a screen of such for trypsin inhibition and subsequent
      partial Edman degradation of the peak active fraction derived the sequence: ATKPR
      QYIVL-PRILRPV-GT. The molecular mass of the major component in this fraction was
      established by MALDI-TOF MS as 5893.09 Da. This partial sequence (assuming blank
      cycles to be Cys residues) was used to design a degenerate primer pool that was
      employed successfully in RACE-PCR to clone homologous precursor-encoding cDNA
      that encoded a mature Kazal protein of 52 amino acid residues with a computed
      molecular mass of 5892.82 Da. The protein was named A. callidryas Kazal trypsin
      inhibitor (ACKTI). BLAST analysis revealed that ACKTI contained a canonical Kazal
      motif (C-x(7)-C-x(6)-Y-x(3)-C-x(2,3)-C). This novel amphibian skin Kazal trypsin
      inhibitor adds to the spectrum of trypsin inhibitors of Kunitz- and Bowman Birk
      type reported from this amphibian source.

PMID- 22464956
TI  - Activity pattern of a selected group of school occupants and their family members
      in Helsinki-Finland.
AB  - The daily time-spent in different environments is an important factor in
      calculation of personal exposure to air pollutants. Despite this importance, the
      amount of research done on this topic is rather limited, especially in North
      Europe where the climate is rather cold. In this study, we gathered detailed
      information via a standard questionnaire to report the residence time and place
      of 167 subjects (between 2 and 93 years old) lived in Helsinki during three time
      periods in winter and spring 2009. Subjects spent 81%-92% of their time indoors
      and up to ~15% of their time outdoors. The daily time-spent in different
      environments was affected by several factors: ambient temperature, type of day
      (workday or weekend/holiday), gender, and age. Therefore, the differences occur
      individually and can be explained by these factors. For example, subjects spent
      more time at home on weekends than workdays because obviously the majority of our
      subjects did not have work on weekends. The time-spent at
      kindergarten/school/work increased with age until retirement. Females spent more
      time at home than males. After all, the activity pattern found in this study is
      rather similar to those previously reported in Germany and North America.

PMID- 22464957
TI  - Contribution of volcanic ashes to the regional geochemical balance: the 2008
      eruption of Chaiten volcano, Southern Chile.
AB  - The environmental geochemical behaviour of the rhyolitic ashes from the 2008
      eruption of Chaiten volcano, Southern Chile, has been studied. After the bulk
      characterisation, the potential contribution to the regional geochemical fluxes
      was examined using: i) single batch leaching tests to provide a rapid screening
      of the implied major and trace elements; and ii) column experiments to evaluate
      the temporal mobility of leached elements. The environmental concerns of these
      ashes are related to the fine grained component present in each sample
      (independent of distance from the source), in particular the presence of
      cristobalite, and the geochemical hazards posed by ash-water interaction.
      Leaching experiments show the fast dissolution of surface salts and aerosols,
      which dominate over glass dissolution during the first steps of the ash-water
      interaction. Chaiten ashes could transfer to the environment more than 1*10(10)g
      or 10,000 metric tonnes (mt) of Cl, S, Ca, Na, Si, and K; between 1000 and 10,000
      mt of F, Mg, and Al; between 100 and 1000 mt of As, Pb, P, Fe, Sr, Zn, Mn, and
      Br; between 10 and 100 mt of Ba, Li, Ti, Ni, Nb, Cu, Rb, Zr, V, Mo, Co, and Sc;
      and less than 10 mt of Cr, Sb, Ce, Ga, Cs, and Y. These results show the
      fertilising potential of the ashes (e.g., providing Ca and Fe) but also the input
      of potentially toxic trace elements (e.g., F and As) in the regional geochemical
      mass balance. The Chaiten results evidence lower potentials for poisoning and
      fertilising than low silica ashes due to the lower contents released of
      practically all elements.

PMID- 22464958
TI  - Gradient analysis reveals a copper paradox on floodplain soils under long-term
      pollution by mining waste.
AB  - Arable alluvial soils are a globally important resource under increasing pressure
      from both industrial pollution and intensified agricultural land use. Quality of
      agricultural soils is ultimately defined by crop yields; it is however seldom
      feasible to study the consequences of complex soil pollution on crops under field
      conditions. This work analyses the long term effects of two gradients: spatial
      (relative distance from the water channel) and land use intensity (cropping
      frequency) on soil properties and model crop (barley) response. On an exceptional
      model locality in Eastern Serbia, degraded by fluvial deposition of sulphidic
      copper tailings during 50 years, multivariate analysis shows that land use
      accelerates the substitution of high plant available Cu by nutrient deficiency
      (primarily P and microelements) and excessive exchangeable Al. Though agronomic
      soil quality might not differ along the land use gradient, the environmental
      consequences do drastically change. The observed apparent "paradoxes" (e.g. soil
      Cu decreases towards the pollution source; higher yields might coincide with
      higher soil and leaf Cu concentrations; and leaching of Cu does not restore soils
      agronomic quality) can be explained by a) the Cu retention patterns along the
      transects, b) importance of higher SOM and nutrient availability for
      modifications of Cu toxicity, and c) the existence of plant adaptation mechanisms
      which can considerably counteract the adverse soil conditions. Land use-induced
      nutrient deficiency can counteract the positive effects of decreased Cu levels.
      In a long run, accelerated Cu mobilisation is likely to increase vulnerability of
      these soils to further environmental hazards. This study demonstrates the clear
      and consistent patterns in soil properties and plant response along the gradients
      and points out the probable long-term environmental trends in a "would be"
      scenario for agricultural use of similar polluted soils.

PMID- 22464959
TI  - An empirical research of awareness, behavior and barriers to enact carbon
      management of industrial firms in China.
AB  - Knowledge of awareness, behavior and barriers to putting carbon management in
      place is particularly useful for policy-makers in providing favorable conditions
      in support of firms' climate change adaptation measures. According to unique data
      from in-depth interviews with firms from the most fossil fuel-intensive
      industries in Fujian, China, the present study indicated that the firms were
      relatively well informed of the knowledge and value of carbon management, and had
      a strong willingness to act. Nevertheless, there was no indication of actual
      behavior by these firms to enact carbon management, and a striking gap existed
      between awareness and behavior. The results also indicated the barriers, which
      were categorized into structural, regulatory, contextual and cultural. These
      barriers and their mutually reinforcing effects hampered the process of
      translating awareness into actual behavior.

PMID- 22464960
TI  - Bioconcentration of pesticides in zebrafish eleutheroembryos (Danio rerio).
AB  - The feasibility of a bioaccumulation test based on the use of zebrafish
      eleutheroembryos as an alternative to adult-individual-based approaches for REACH
      application has been evaluated for three test compounds, chlorpyrifos, dicofol
      and atrazine. Following the OECD 305 guidelines, zebrafish eleutheroembryos (72 h
      after hatching, hpf) were separately exposed to the investigated pesticides at
      two nominal concentrations below 1% of its corresponding LC(50). The uptake
      experiments lasted for 48 h. Then, the exposure medium was replaced by a non
      contaminated medium for depuration experiments (up to 72 h). Zebrafish
      eleutheroembryos (larvae 144 hpf, i.e. at the end of the depuration step) and
      their corresponding exposure media was sampled at ten different times during each
      experiment and the concentration of the investigated pesticide determined in both
      the organisms and in the exposure medium. The experimentally determined pesticide
      accumulation profiles in the eleutheroembryos demonstrated that atrazine has a
      very fast accumulation kinetic, reaching steady sate (SS) within 24h.
      Chlorpyrifos and dicofol did not reach the SS within the 48-h uptake experiments
      although they exhibit higher accumulations than the former pesticide. Two
      toxicokinetic models were used to calculate the bioconcentration factor (BCF) of
      the studied pesticide in zebrafish eleutheroembryos. In the former, the BCF was
      calculated under SS conditions (BCF(SS)). The second was used when the compounds
      did not reach the SS during the uptake experiment (BCF(k)). Log BCF values of
      3.55 and 3.84 for chlorpyrifos; 0.6 and 1.17 for atrazine, and 3.90 for dicofol
      were experimentally calculated at selected exposure concentrations. These values
      have been compared with those reported in related bioaccumulation studies and
      official databases.

PMID- 22464961
TI  - Stone-isolated carbonatogenic bacteria as inoculants in bioconsolidation
      treatments for historical limestone.
AB  - Stone consolidation treatments that use bacterial biomineralization are mainly
      based on two strategies: (1) the inoculation of a bacterial culture with proven
      carbonatogenic ability and/or (2) the application of a culture medium capable of
      activating those bacteria able to induce the formation of calcium carbonate, from
      amongst the bacterial community of the stone. While the second strategy has been
      demonstrated to be effective and, unlike first strategy, it does not introduce
      any exogenous microorganism into the stone, problems may arise when the bacterial
      community of the stone is altered, for instance by the use of biocides in the
      cleaning process. In this study we isolate bacteria that belong to the natural
      microbial community of the stone and which have proven biomineralization
      capabilities, with the aim of preparing an inoculum that may be used in stone
      consolidation treatments wherein the natural community of those stones is
      altered. With this aim, outdoor experiments were undertaken to activate and
      isolate bacteria that display high biomineralization capacity from altered
      calcarenite stone. Most of the bacteria precipitated calcium carbonate in the
      form of calcite. The selected bacteria were phylogenetically affiliated with
      members of Actinobacteria, Gamma-proteobacteria and Firmicutes. Furthermore, the
      capability of these selected carbonatogenic bacteria to consolidate altered
      calcarenite stone slabs was studied in in vitro experiments, both in the presence
      and the absence of Myxococcus xanthus, as a potential reinforcement for the
      bacterial biomineralization. Herein, Acinetobacter species, belonging to the
      microbial community of the stone, are proposed as powerful carbonatogenic
      bacteria that, inoculated under appropriate conditions, may be used as inoculum
      for calcareous stone conservation/consolidation in restoration interventions
      where the microbial community of the stone is altered.

PMID- 22464962
TI  - Soil-plant interactions and the uptake of Pb at abandoned mining sites in the
      Rookhope catchment of the N. Pennines, UK--a Pb isotope study.
AB  - This paper examines Pb concentrations and sources in soil, grass and heather from
      the Rookhope catchment in the North Pennines, UK, an area of historical Pb and Zn
      mining and smelting. Currently, the area has extensive livestock and sports
      shooting industries. Risk assessment, using the source-pathway-receptor paradigm,
      requires the quantification of source terms and an understanding of the many
      factors determining the concentration of Pb in plants. A paired soil and
      vegetation (grass and heather) geochemical survey was undertaken. Results showed
      no direct correlation between soil (total or EDTA extractable Pb) and vegetation
      Pb concentration. However, regression modelling based on the Free-Ion Activity
      Model (FIAM) suggested that the underlying mechanism determining grass Pb
      concentration across the catchment was largely through root uptake. Spatial
      patterns of (206/207)Pb isotopes suggested greater aerosol deposition of Pb on
      high moorland and prevailing wind facing slopes. This was evident in the isotopic
      ratios of the heather plants. Pb isotope analysis showed that new growth heather
      tips typically had (206/207)Pb values of ~1.14, whilst grass shoots typically had
      values ~1.16 and bulk soil and peat ~1.18. However, the (206/207)Pb ratio in the
      top few cm of peat was ~1.16 suggesting that grass was accessing Pb from a
      historical/recent pool of Pb in soil/peat profiles and consisting of both Pennine
      ore Pb and long-range Pb deposition. Isotope Dilution assays on the peat showed a
      lability of between 40 and 60%. A simple source apportionment model applied to
      samples where the isotope ratios was not within the range of the local Pennine
      Pb, suggested that grass samples contained up to 31% of non-Pennine Pb. This
      suggests that the historical/recent reservoir of non-Pennine Pb accessed by roots
      continues to be a persistent contaminant source despite the principal petrol Pb
      source being phased out over a decade ago.

PMID- 22464963
TI  - The potential economic value of a Staphylococcus aureus vaccine among
      hemodialysis patients.
AB  - Staphylococcus aureus infections are a substantial problem for hemodialysis
      patients. Several vaccine candidates are currently under development, with
      hemodialysis patients being one possible target population. To determine the
      potential economic value of an S. aureus vaccine among hemodialysis patients, we
      developed a Markov decision analytic computer simulation model. When S. aureus
      colonization prevalence was 1%, the incremental cost-effectiveness ratio (ICER)
      of vaccination was <=$25,217/quality-adjusted life year (QALY). Vaccination
      became more cost-effective as colonization prevalence, vaccine efficacy, or
      vaccine protection duration increased or vaccine cost decreased. Even at 10%
      colonization prevalence, a 25% efficacious vaccine costing $100 prevented 29
      infections, 21 infection-related hospitalizations, and 9 inpatient deaths per
      1000 vaccinated HD patients. Our results suggest that an S. aureus vaccine would
      be cost-effective (i.e., ICERs <= $50,000/QALY) among hemodialysis patients over
      a wide range of S. aureus prevalence, vaccine costs and efficacies, and vaccine
      protection durations and delineate potential target parameters for such a
      vaccine.

PMID- 22464965
TI  - Identification and optimization of critical process parameters for the production
      of NOMV vaccine against Neisseria meningitidis.
AB  - Outer membrane vesicles (OMV) are used as a vaccine against Neisseria
      meningitidis serogroup B and are traditionally produced with detergent-extraction
      to remove toxic lipopolysaccharide. Engineered strains with attenuated
      lipopolysaccharide allowed the use of native vesicles (NOMV) with improved
      stability and immunogenicity. In the NOMV production process detergents are
      omitted and vesicle release is stimulated with EDTA extraction (a chelating
      agent) to enable a higher yield. Many process parameters may change the EDTA
      extraction efficiency, but it is unknown what the optimal ranges for these
      parameters are in terms of quality. The present study systematically optimized
      EDTA extraction and was representative for production at large-scale. Two
      critical process parameters were identified, harvest point of the cultivation
      (harvest) and pH of the extraction buffer (pH), which significantly affected
      yield (7-fold) and bacterial lysis (35-fold). The other quality attributes
      remained unchanged. Optimization of harvest and pH revealed that the desired low
      bacterial lysis coincided with intermediate but sufficient yield. High functional
      immunogenicity and low toxicity of the optimized vaccine were also confirmed. The
      EDTA extraction is therefore a robust process step which produces high quality
      OMV if harvest and pH are controlled accurately.

PMID- 22464964
TI  - Induction of mucosal HIV-specific B and T cell responses after oral immunization
      with live coxsackievirus B4 recombinants.
AB  - Given the limited success of clinical HIV vaccine trials, new vaccine strategies
      are needed for the HIV pipeline. The present study explored the novel concept
      that a live enteric virus, with limited disease potential, is a suitable vaccine
      vector to elicit HIV-specific immune responses in the gut mucosa of immunized
      mice. Two coxsackievirus B4 (CVB4) vaccine vectors were designed to induce HIV
      specific B or T cell responses. A B cell immunogen, CVB4/gp41(2F5), was
      constructed by expressing an epitope from the membrane proximal external region
      (MPER) of gp41 as a structural peptide within a surface loop of a capsid protein
      of CVB4. The T cell immunogen, CVB4/p24(73(3)), was constructed previously by
      expressing a gag p24 sequence as a non-structural peptide at the amino-terminus
      of the CVB4 polyprotein. The CVB4/gp41(2F5) recombinant was antigenic in mice and
      elicited anti-gp41 antibodies in both the mucosal and systemic compartments. The
      route of immunization affected the antibody response since oral delivery of
      CVB4/gp41(2F5) induced anti-gp41 antibodies in the mucosal but not in the
      systemic compartment while parenteral delivery induced anti-gp41 antibodies in
      both compartments. In contrast, oral immunization with CVB4/p24(73(3)) elicited
      both mucosal and systemic gag p24-specific T cell responses. Since
      coxsackieviruses are ubiquitous in the human population, a key question is
      whether pre-existing vector immunity will inhibit the ability of a CVB4-based
      vaccine to induce HIV-specific immune responses. We show that pre-existing vector
      immunity did not preclude the development of mucosal anti-gp41 antibodies or gag
      p24-specific T cell responses after oral immunization with the CVB4/HIV
      recombinants. We suggest that the CVB4/HIV recombinants have the potential to be
      a viable vaccine product because of ease of delivery, safety, immunogenicity,
      ease of large-scale production, and storage conditions requiring cold-chain
      temperatures provided by refrigeration.

PMID- 22464966
TI  - Protection against pneumococcal infection elicited by immunization with glutamyl
      tRNA synthetase, polyamine transport protein D and sortase A.
AB  - Protein-based vaccines are considered to be the next-generation of pneumococcal
      vaccines. Here we evaluated the protection elicited by immunization with
      recombinant glutamyl tRNA synthetase (Gts), polyamine transport protein D (PotD)
      and sortase A (SrtA) antigens in preclinical mouse models. In mucosal
      immunization studies, intranasal immunization with either Gts, PotD or SrtA could
      significantly reduce pneumococcal nasopharyngeal and lung colonization and
      significantly increase mice survival times following invasive pneumococcal
      challenge, and combinations of these antigens could enhance this protection. In
      systemic immunization studies, intraperitoneal immunization with multiple protein
      antigens also provided better protection against pneumococcal sepsis caused by
      different pneumococcal strains. Finally, passive immunization studies showed an
      additive effect by using multiple anti-sera when compared to single anti-sera.
      Therefore, a multicomponent protein-based pneumococcal vaccine composed of Gts,
      PotD or SrtA could confer protection against pneumococcal colonization as well as
      invasive infections in terms of efficacy of protection and serotype coverage.

PMID- 22464967
TI  - Generation of a live rabies vaccine strain attenuated by multiple mutations and
      evaluation of its safety and efficacy.
AB  - An amino acid substitution at position 333 in rabies virus G protein is known to
      determine the pathogenicity: strains with Arg or Lys at that position kill adult
      mice after intracerebral inoculation, whereas strains with other amino acids
      cause non-lethal infection. Based on those findings, attenuated rabies virus
      strains have been established and used for oral vaccines mainly for wild animals.
      However, considering the possibility of back-mutation to the virulent phenotype,
      a strain that is attenuated by multiple mutations not only in the G protein but
      also in other viral proteins would be more appropriate as a safe live vaccine. We
      previously demonstrated that the fixed rabies virus Ni-CE strain, which causes
      only transient body weight loss in adult mice after intracerebral inoculation, is
      mainly attenuated by mutations in the N, P and M proteins, while this strain has
      virulent-type Arg at position 333 in the G protein. In this study, to obtain a
      live vaccine strain that is attenuated by multiple mutations, we generated Ni-CE
      mutant, Ni-CE(G333Glu) strain, which has an Arg-to-Glu mutation at position 333
      in the G protein, and examined its pathogenicity and immunogenicity. We found
      that, in contrast to Ni-CE strain, Ni-CE(G333Glu) strain did not cause transient
      body weight loss in adult mice after intracerebral inoculation. The attenuated
      phenotype of Ni-CE(G333Glu) strain did not change even after 10 serial
      intracerebral passages in suckling mice. We also demonstrated that inoculation of
      Ni-CE(G333Glu) strain induced virus-neutralizing antibody in immunized mice and
      protected the mice from lethal challenge. These results indicate that Ni
      CE(G333Glu) strain is a promising candidate for development of a live rabies
      vaccine with a high safety level.

PMID- 22464968
TI  - Vaccines - the key paradigm for the 21st century's health care strategy: 5th
      Semmering vaccine symposium, Baden/Vienna. Editorial.

PMID- 22464969
TI  - Control of pandemic (H1N1) 2009 influenza virus infection of ferret lungs by non
      adjuvant-containing pandemic and seasonal vaccines.
AB  - The pandemic H1N1 2009 influenza virus caused relatively mild disease in most
      infected people but some suffered extensively from primary lung infection, many
      more than would have occurred with seasonal influenza infection. Early
      commercially available pandemic H1N1 vaccines did not contain adjuvant, as did
      many of the subsequent vaccines, and could not stop infection with the pandemic
      virus in vaccinated ferrets. Nevertheless, we showed that virus loads in the
      lungs were greatly diminished in ferrets vaccinated once with an unadjuvanted
      pandemic vaccine and challenged with 10(6)EID(50) wildtype A/California/07/2009
      (H1N1). In addition, a single inoculation with seasonal vaccine showed beneficial
      reduction in pandemic pulmonary virus loads in the absence of any detectable
      cross-reactive serological responses. Ferrets primed with either seasonal or
      pandemic vaccine and then boosted with pandemic vaccine also showed less
      extensive lung infection when challenged with a tenfold higher dose of pandemic
      virus. These results implicate non-classical protective mechanisms that prevent
      severe pulmonary disease but not viral shedding and imply that particular non
      adjuvanted vaccines may have retained the ability to induce these responses.

PMID- 22464970
TI  - Structure, activity and interactions of the cysteine deleted analog of
      tachyplesin-1 with lipopolysaccharide micelle: Mechanistic insights into outer
      membrane permeabilization and endotoxin neutralization.
AB  - Tachyplesin-1, a disulfide stabilized beta-hairpin antimicrobial peptide, can be
      found at the hemocytes of horse shoe crab Tachypleus tridentatus. A cysteine
      deleted linear analog of tachyplesin-1 or CDT (KWFRVYRGIYRRR-NH2) contains a
      broad spectrum of bactericidal activity with a reduced hemolytic property. The
      bactericidal activity of CDT stems from selective interactions with the
      negatively charged lipids including LPS. In this work, CDT-LPS interactions were
      investigated using NMR spectroscopy, optical spectroscopy and functional assays.
      We found that CDT neutralized LPS and disrupted permeability barrier of the outer
      membrane. Zeta potential and ITC studies demonstrated charge compensation and
      hydrophobic interactions of CDT with the LPS-outer membrane, respectively.
      Secondary structure of the peptide was probed by CD and FT-IR experiments
      indicating beta-strands and/or beta-turn conformations in the LPS micelle. An
      ensemble of structures, determined in LPS micelle by NMR, revealed a beta-hairpin
      like topology of the CDT peptide that was typified by an extended cationic
      surface and a relatively shorter segment of hydrophobic region. Interestingly, at
      the non-polar face, residue R11 was found to be in a close proximity to the
      indole ring of W2, suggesting a cation-n type interactions. Further, saturation
      transfer difference (STD) NMR studies established intimate contacts among the
      aromatic and cationic residues of CDT with the LPS micelle. Fluorescence and
      dynamic light scattering experiments demonstrated that CDT imparted structural
      destabilization to the aggregated states of LPS. Collectively, atomic resolution
      structure and interactions of CDT with the outer membrane-LPS could be exploited
      for developing potent broad spectrum antimicrobial and anti-sepsis agents.

PMID- 22464972
TI  - Transcriptional mechanisms of developmental cell cycle arrest: problems and
      models.
AB  - Metazoans begin their life as a single cell. Then, this cell enters a more or
      less protracted period of active cell proliferation, which can be considered as
      the default cellular state. A crucial event, the developmental cell cycle exit,
      occurs thereafter. This phenomenon allows for differentiation to happen and
      regulates the final size of organs and organisms. Its control is still poorly
      understood. Herein, we review some transcriptional mechanisms of cell cycle exit
      in animals, and propose to use cellular conveyor belts as model systems for its
      study. We finally point to evidence that suggests that the mechanisms of
      developmental cell cycle arrest may have to be maintained in adult tissues.

PMID- 22464971
TI  - Oxidized phospholipids as biomarkers of tissue and cell damage with a focus on
      cardiolipin.
AB  - Oxidized phospholipid species are important, biologically relevant, lipid
      signaling molecules that usually exist in low abundance in biological tissues.
      Along with their inherent stability issues, these oxidized lipids present
      themselves as a challenge in their detection and identification. Often times,
      oxidized lipid species can co-chromatograph with non-oxidized species making the
      detection of the former extremely difficult, even with the use of mass
      spectrometry. In this study, a normal-phase and reverse-phase two dimensional
      high performance liquid chromatography (HPLC)-mass spectrometric system was
      applied to separate oxidized phospholipids from their non-oxidized counterparts,
      allowing unambiguous detection in a total lipid extract. We have utilized bovine
      heart cardiolipin as well as commercially available tetralinoleoyl cardiolipin
      oxidized with cytochrome c (cyt c) and hydrogen peroxide as well as with
      lipoxygenase to test the separation power of the system. Our findings indicate
      that oxidized species of not only cardiolipin, but other phospholipid species,
      can be effectively separated from their non-oxidized counterparts in this two
      dimensional system. We utilized three types of biological tissues and oxidative
      insults, namely rotenone treatment of lymphocytes to induce mitochondrial damage
      and cell death, pulmonary inhalation exposure to single walled carbon nanotubes,
      as well as total body irradiation, in order to identify cardiolipin oxidation
      products, critical to the cell damage/cell death pathways in these tissues
      following cellular stress/injury. Our results indicate that selective cardiolipin
      (CL) oxidation is a result of a non-random free radical process. In addition, we
      assessed the ability of the system to identify CL oxidation products in the
      brain, a tissue known for its extreme complexity and diversity of CL species. The
      ability of the two dimensional HPLC-mass spectrometric system to detect and
      characterize oxidized lipid products will allow new studies to be formulated to
      probe the answers to biologically important questions with regard to oxidative
      lipidomics and cellular insult. This article is part of a Special Issue entitled:
      Oxidized phospholipids - their properties and interactions with proteins.

PMID- 22464973
TI  - A double-blind, randomized, placebo-controlled study with JNJ-37822681, a novel,
      highly selective, fast dissociating D2 receptor antagonist in the treatment of
      acute exacerbation of schizophrenia.
AB  - JNJ-37822681 is a novel, highly selective dopamine D2 receptor antagonist
      characterized by a rapid dissociation rate from the dopamine D2 receptor. This
      profile was hypothesized to confer antipsychotic efficacy and improved
      tolerability. In this 12-week study, the efficacy and safety of JNJ-37822681 were
      evaluated in patients with an acute exacerbation of schizophrenia, randomly
      assigned (1:1:1:1:1) to JNJ-37822681 (10-, 20- or 30-mg bid), olanzapine (15 mg
      once-daily), or placebo (for 6 weeks followed by olanzapine for 6 weeks). Of 498
      randomized patients, 298 (60%) completed the study. All JNJ-37822681 dose groups
      and the olanzapine group showed significantly greater reduction in PANSS total
      score from baseline to week 6 versus placebo (all p-values < 0.001). Least
      squares adjusted mean changes from baseline to week 6 in PANSS total score were: 
      6.4 (placebo); -18.4 (10 mg JNJ-37822681), -17.7 (20 mg JNJ-37822681), -20.0 (30
      mg JNJ-37822681) and -22.9 (olanzapine). All JNJ-37822681 groups showed
      significant improvement versus placebo from baseline to week 6 in the PANSS
      subscales, Marder factors, Clinical Global Impression of Severity, and in the
      Subjective Well-Being on Neuroleptics scale (all p-values < 0.05). The most
      common treatment-emergent adverse events with JNJ-37822681 were insomnia (17%)
      and akathisia (13%). Incidences of extrapyramidal symptoms were dose-related and
      were comparable for JNJ-37822681 10 mg bid and olanzapine groups. All JNJ
      37822681 dose groups showed lesser weight gain compared with olanzapine. The
      efficacy and tolerability profile of the JNJ-37822681 10 mg bid was consistent
      with the study hypothesis.

PMID- 22464974
TI  - [Surgical treatment of intrathoracic goitre].
AB  - The definition by Katlic gives the best description of intrathoracic goitre, a
      condition that includes a small sub-group (1-4%) of patients with multinodular
      goitre who generally have severe compression symptoms and require specialised
      care in reference centres. The pre-operative study must include thoracic imaging
      techniques to plan the most suitable action. Total thyroidectomy is recommended,
      and in more than 95% of cases the goitre can be removed using a cervical
      approach. A wide cervical approach and the identification of the recurrent nerve
      near the cricothyroid joint help to free the thyroid from all its cervical
      attachments before gently retracting it upwards from the thoracic component for
      its removal. Intrathoracic goitres that require a sternotomy for its removal are
      recurrent goitres, those that have advanced cancer, those that reach the carina,
      and left posterior goitres that extend to the right pleural cavity.

PMID- 22464975
TI  - [Technology, technophilia... or technophobia?].

PMID- 22464976
TI  - The active stem cell specific expression of sponge Musashi homolog EflMsiA
      suggests its involvement in maintaining the stem cell state.
AB  - A hallmark of stem cells is the ability to sustainably generate stem cells
      themselves (self-renew) as well as differentiated cells. Although a full
      understanding of this ability will require clarifying underlying the primordial
      molecular and cellular mechanisms, how stem cells maintain their stem state and
      their population in the evolutionarily oldest extant multicellular organisms,
      sponges, is poorly understood. Here, we report the identification of the first
      stem cell-specific gene in demosponges, a homolog of Musashi (an evolutionarily
      conserved RNA binding protein that regulates the stem cell state in various
      organisms). EflMsiA, a Musashi paralog, is specifically expressed in stem cells
      (archeocytes) in the freshwater sponge Ephydatia fluviatilis. EflMsiA protein is
      localized predominantly in the nucleus, with a small fraction in the cytoplasm,
      in archeocytes. When archeocytes enter M-phase, EflMsiA protein diffuses into the
      cytoplasm, probably because of the breakdown of the nuclear membrane. In the
      present study, the existence of two types of M-phase archeocytes [(M)
      archeocytes] was revealed by a precise analysis of the expression levels of
      EflMsiA mRNA and protein. In Type I (M)-archeocytes, presumably archeocytes
      undergoing self-renewal, the expression levels of EflMsiA mRNA and protein were
      high. In Type II (M)-archeocytes, presumably archeocytes committed to
      differentiate (committed archeocytes), the expression levels of EflMsiA mRNA and
      protein were about 60% and 30% lower than those in Type I (M)-archeocytes. From
      these results, archeocytes can be molecularly defined for the first time as
      EflMsiA-mRNA-expressing cells. Furthermore, these findings shed light on the mode
      of cell division of archeocytes and suggest that archeocytes divide symmetrically
      for both self-renewal and differentiation.

PMID- 22464978
TI  - Look who's walking: social and environmental correlates of children's walking in
      London.
AB  - A substantial literature examines the social and environmental correlates of
      walking to school but less addresses walking outside the school commute. Using
      travel diary data from London, we examined social and environmental correlates of
      walking: to school; outside the school commute during term time; and during the
      summer and weekends. Living in a household without a car was associated with all
      journey types; 'Asian' ethnicity was negatively associated with walking for non
      school travel; environmental factors were associated with non-school journeys,
      but not the school commute. Interventions aiming to increase children's active
      travel need to take account of the range of journeys they make.

PMID- 22464977
TI  - Nuclear organization of the serotonergic system in the brain of the rock cavy
      (Kerodon rupestris).
AB  - Serotonin, or 5-hydroxytryptamine (5-HT), is a substance found in many tissues of
      the body, including as a neurotransmitter in the nervous system, where it can
      exert different post-synaptic actions. Inside the neuro-axis, 5-HT neurons are
      almost entirely restricted to the raphe nuclei of the brainstem. As such, 5-HT
      immunoreactivity has been considered a marker of the raphe nuclei, which are
      located in the brainstem, at or near the midline. The present study investigated
      distribution of serotonergic neurons in the brain of the rock cavy (Kerodon
      rupestris), a rodent species inhabiting the Brazilian Northeast. The
      cytoarchitectonic location of serotonergic neurons was established through a
      series of 5-HT immunostained sections, compared with diagrams obtained from
      adjacent coronal and sagittal sections stained by the Nissl method. The following
      nuclei were defined: the rostral group, consisting of rostral linear raphe,
      caudal linear raphe, median and paramedian raphe, dorsal raphe, and pontine raphe
      nuclei, and the caudal group composed of raphe magnus, raphe pallidus and raphe
      obscurus nuclei. Other serotonergic neuronal clusters, such as the supralemniscal
      group and the rostral and caudal ventrolateral medulla oblongata clusters, were
      found outside the midline. Rare 5-HT-producing neurons were identified in the
      lateral parabrachial nucleus and in the pontine reticular formation, mostly along
      fibers of the lateral lemniscus. Despite exhibiting some specializations, the
      picture outlined for serotonergic groups in the rock cavy brain is comparable to
      that described for other mammalian species.

PMID- 22464979
TI  - Does the Food Stamp Program cause obesity? A realist review and a call for place
      based research.
AB  - The high prevalence of obesity among low income groups has led some to question
      the role of food assistance programs in contributing to the problem. The USDA's
      Food Stamp Program (now known as the Supplemental Nutrition Assistance Program -
      SNAP) is the largest food assistance program in the United States with over 40
      million participants. This paper employed systematic realist review methods to
      determine whether participation in the Food Stamp Program causes obesity and the
      causal pathways through which this relationship may exist. Findings indicate a
      more consistent positive relationship for women than for men, especially for
      women who are long term users of the program. All studies discussed the "food
      stamp cycle" and an "income effect" as explanations for the role of food stamps
      in increased obesity yet evidence for these factors is limited. Curiously, the
      research in this field does not address obesogenic environments and we suggest
      that the absence of an understanding of household behavior in local contexts is a
      significant impediment to the reform of the Food Stamp Program.

PMID- 22464980
TI  - Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated
      efflux.
AB  - There is concern that P-glycoprotein mediated efflux contributes to steroid
      resistance. Therefore, this study examined bidirectional corticosteroid transport
      and induction capabilities for P-glycoprotein (P-gp) to understand which of the
      systemic and inhaled corticosteroids interacted with P-gp to the greatest extent.
      Hydrocortisone, prednisolone, prednisone, methylprednisolone, and dexamethasone
      represented systemically active drugs, while fluticasone propionate,
      beclomethasone dipropionate, ciclesonide and budesonide represented inhaled
      corticosteroids. Aldosterone and fludrocortisone represented mineralocorticoids.
      All drugs were detected using individually optimised HPLC protocols. Transport
      studies were conducted through Caco-2 monolayers. Hydrocortisone and aldosterone
      had efflux ratios below 1.5, while prednisone showed a P-gp mediated efflux ratio
      of only 1.8 compared to its active drug, prednisolone, with an efflux ratio of
      4.5. Dexamethasone and beclomethasone had efflux ratios of 2.1 and 3.3
      respectively, while this increased to 5.1 for methylprednisolone. Fluticasone
      showed an efflux ratio of 2.3. Protein expression studies suggested that all of
      the inhaled corticosteroids were able to induce P-gp expression, from 1.6 to 2
      times control levels. Most of the systemic corticosteroids had higher passive
      permeability (>20*10(-6) cm/s) compared to the inhaled corticosteroids (>5*10(-6)
      cm/s), except for budesonide, with permeability similar to the systemic
      corticosteroids. Inhaled corticosteroids are not transported by P-gp to the same
      extent as systemic corticosteroids. However, they are able to induce P-gp
      production. Thus, inhaled corticosteroids may have greater interactions with
      other P-gp substrates, but P-gp itself is less likely to influence resistance to
      the drugs.

PMID- 22464981
TI  - Comparison of COD removal from pharmaceutical wastewater by electrocoagulation,
      photoelectrocoagulation, peroxi-electrocoagulation and peroxi
      photoelectrocoagulation processes.
AB  - This work makes a comparison between electrocoagulation (EC),
      photoelectrocoagulation, peroxi-electrocoagulation and peroxi
      photoelectrocoagulation processes to investigate the removal of chemical oxygen
      demand (COD) from pharmaceutical wastewater. The effects of operational
      parameters such as initial pH, current density, applied voltage, amount of
      hydrogen peroxide and electrolysis time on COD removal efficiency were
      investigated and the optimum operating range for each of these operating
      variables was experimentally determined. In electrocoagulation process, the
      optimum values of pH and voltage were determined to be 7 and 40 V, respectively.
      Desired pH and hydrogen peroxide concentration in the Fenton-based processes were
      found to be 3 and 300 mg/L, respectively. The amounts of COD, pH, electrical
      conductivity, temperature and total dissolved solids (TDS) were on-line
      monitored. Results indicated that under the optimum operating range for each
      process, the COD removal efficiency was in order of peroxi-electrocoagulation >
      peroxi-photoelectrocoagulation > photoelectrocoagulation>electrocoagulation.
      Finally, a kinetic study was carried out using the linear pseudo-second-order
      model and results showed that the pseudo-second-order equation provided the best
      correlation for the COD removal rate.

PMID- 22464982
TI  - Cuprous oxide created on sepiolite: preparation, characterization, and
      photocatalytic activity in treatment of red water from 2,4,6-trinitrotoluene
      manufacturing.
AB  - Cuprous oxide is firstly created on acidized sepiolite (AS) by a simple
      deposition method for photocatalytic degradation of the red water produced from
      2,4,6-trinitrotoluene (TNT) manufacturing. X-ray diffraction (XRD), field
      emission scanning electron microscopy (FE-SEM), ultraviolet-visible diffuse
      reflection absorptive spectroscopy (UV-vis/DRS), and Fourier transform infrared
      (FT-IR) spectroscopy are used to characterize the photocatalyst composites. Gas
      chromatography/mass spectrometry (GC/MS) is employed to determine the organic
      constituents in the red water. The results show that the cuprous oxide particles
      can be immobilized on the surface of the AS fibers and the structure of the AS is
      altered when cuprous oxide interacts with AS via chemical reactions besides
      physical adsorption. The AS improves the optical properties of cuprous oxide and
      red-shifts the band gap thereby enhancing the utilization of visible light. The
      Cu(2)O/AS composites demonstrate excellent photocatalytic performance in the
      degradation of red water. 87.0% of red water can be photocatalytically degraded
      by Cu(2)O/AS after illumined for 5h and a majority of organic components of red
      water except 1,3,5-trinitrobenzene were degraded according to GC-MS analysis.

PMID- 22464983
TI  - Arsenate immobilization associated with microbial oxidation of ferrous ion in
      complex acid sulfate water.
AB  - Chemical, XRD, SEM, RS, FTIR and XPS techniques were used to investigate arsenate
      immobilization associated with microbial Fe(2+) oxidation in a complex acid
      sulfate water system consisting of a modified 9 K solution (pH 2.0) plus As, Cu,
      Cd, Pb, Zn and Mn. At a 1:12.5:70 molar ratio of As:Fe:S, schweretmannite
      formation was impeded. This was in contrast with the predominant presence of
      schwertmannite when the heavy metals were absent, suggesting that a
      schwertmannite binding model is not valid for explaining arsenate immobilization
      in the complex system. In this study, arsenate was initially immobilized through
      co-precipitation with non-Fe metals and phosphate. Subsequently when sufficient
      Fe(3+) was produced from Fe(2+) oxidation, formation of a mixed iron, arsenate
      and phosphate phase predominated. The last stage involved surface complexation of
      arsenate species. Pb appeared to play an insignificant role in arsenate
      immobilization due to its strong affinity for sulfate to form anglesite.
      Phosphate strongly competed with arsenate for the available binding sites.
      However, As exhibited an increased capacity to compete with P and S for available
      binding sites from the co-precipitation to surface complexation stage. Adsorbed
      As tended to be in HAsO(4)(2-) form. The scavenged arsenate species was
      relatively stable after 2464-h aging.

PMID- 22464984
TI  - Genotoxic effects of metal pollution in two fish species, Oreochromis niloticus
      and Mugil cephalus, from highly degraded aquatic habitats.
AB  - In Egypt, Lake Qaroun and its neighbouring fish farms are in a serious
      environmental situation as a result of pollution by agricultural sewage and
      domestic non-treated discharges. The present study aims to evaluate genotoxic
      effects of toxic metals in cultured and wild Nile tilapia, Oreochromis niloticus
      and mullet, Mugil cephalus collected from these contaminated aquatic habitats, in
      comparison with fish from a non-polluted reference site. Heavy-metal
      concentrations (Cu(2+), Zn(2+), Pb(2+), Fe(2+) and Mn(2+)) in water and sediment
      samples were recorded. The condition factor (CF) was taken as a general biomarker
      of the health of the fish, and genotoxicity assays such as the micronucleus (MN)
      test and a DNA-fragmentation assay were carried out on the fish species studied.
      In addition to micronuclei, other nuclear abnormalities (NA) were assessed in
      fish erythrocytes. Degradation of the studied aquatic habitats revealed species
      specific effects. A significant decrease in CF values associated with a
      significant elevation in MN and NA frequencies was observed in fish collected
      from the polluted areas compared with those from the reference site. Moreover,
      mixed smearing and laddering of DNA fragments in gills and liver samples of both
      fish species collected from the polluted areas indicate an intricate pollution
      condition. Results of the present study show the significance of integrating a
      set of biomarkers to identify the effects of anthropogenic pollution. High
      concentrations of heavy metals have a potential genotoxic effects, and
      genotoxicity is possibly related to agricultural and domestic activities.

PMID- 22464985
TI  - Cytogenetic and antineoplastic effects by newly synthesised steroidal alkylators
      in lymphocytic leukaemia P388 cells in vivo.
AB  - New compounds with potential antitumour activity were synthesised by combining
      nitrogen mustard with the steroidal skeleton, in an effort to improve specificity
      and at the same time reduce systemic toxicity. The steroidal part is aimed to
      serve as a biological platform enabling the alkylating moiety to approach its
      site of action by altering its physicochemical properties. The purpose of the
      present investigation was to evaluate these compounds for anti-neoplastic
      activity. The compounds tested have as alkylators either para-NN-bis(2
      chloroethyl)-aminophenyl-butyrate (CHL) or para-N,N-bis(2-chloroethyl)
      aminophenyl-acetate (PHE) esterified with a differently modified steroidal
      nucleus. The eight newly synthesised compounds were compared on a molar basis
      with respect to their ability to induce sister chromatid exchanges (SCEs) and to
      modify proliferation rate indices (PRI) in lymphocytic leukaemia P388 cells in
      mice in vivo. The life span of BDF1 mice inoculated with P388 leukaemia cells was
      also estimated (anti-leukaemic activity). The compounds that were effective in
      inducing cytogenetic effects in lymphocytic leukaemia cells in vivo were also
      effective in inducing antineoplastic effects in BDF1 mice inoculated with P388
      leukaemia cells. These results suggest that the in vivo cytogenetic effects in
      conjunction with the antineoplastic activity of modified steroidal alkylators
      depend on the configuration of the whole molecule and on the appropriate
      combination of the alkylator with the steroidal molecule: a pronounced
      cytogenetic and anti-neoplastic action was demonstrated by the compounds that
      contain either PHE or CHL as alkylators and are esterified with either a
      steroidal nucleus that carries a cholesten group in the 17 position of the D
      ring, or with a steroidal nucleus having an exocyclic NHCO-group in the D-ring.
      In contrast, a ketone group or an NHCO-group in the D-ring inserted
      endocyclically in the steroidal nucleus esterified with either CHL or PHE failed
      to induce cytogenetic or anti-neoplastic effects.

PMID- 22464986
TI  - Effects of Viscum album L. extract and quercetin on methotrexate-induced cyto
      genotoxicity in mouse bone-marrow cells.
AB  - Viscum album, a semi-parasitic plant, has been used both in traditional and
      supplementary medicine in the treatment of many diseases. Quercetin (QE), one of
      the major flavonoids in some fruits and vegetables, has anti-oxidative and anti
      carcinogenic activities. Methotrexate (MTX), an anti-folate anti-metabolite, is a
      widely used anti-neoplastic drug with significant clastogenic effects. The aim of
      this study was to investigate the anti-cytogenotoxic effects of pre-treatment
      with V. album extract (VAE) and QE on MTX-induced chromosomal aberrations (CAs)
      in mouse bone-marrow cells. Pre-treatment of mice by gavage with VAE
      (250mg/kgbw/day for 10 days) and QE (50mg/kgbw/day for 10 days) caused a
      significant decrease in CAs and in the number of aberrant cells with CAs induced
      by intramuscular treatment of the mice with MTX (10mg/kgbw/day for 3 days), when
      compared with the group treated with MTX alone. These compounds also
      significantly increased the mitotic index (MI) in bone-marrow cells that had been
      suppressed by MTX. In conclusion, from the findings we suggest that VAE and QE
      may play a role in reducing cyto-genotoxicity induced by anti-neoplastic drugs
      during cancer chemotherapy.

PMID- 22464987
TI  - Development of tetravalent IgG1 dual targeting IGF-1R-EGFR antibodies with potent
      tumor inhibition.
AB  - In this study we present novel bispecific antibodies that simultaneously target
      the insulin-like growth factor receptor type I (IGF-1R) and epidermal growth
      factor receptor (EGFR). For this purpose disulfide stabilized scFv domains of the
      EGFR/ADCC antibody GA201 were fused via serine-glycine connectors to the C
      terminus of the heavy (XGFR2) or light chain (XGFR4), or the N-termini of the
      light (XGFR5) or heavy chain (XGFR3) of the IGF-1R antibody R1507 as parental
      IgG1 antibody. The resulting bispecific IGF-1R-EGFR antibodies XGFR2, XGFR3 and
      XGFR4 were successfully generated with yields and stability comparable to
      conventional IgG1 antibodies. They effectively inhibited IGF-1R and EGFR
      phosphorylation and 3D proliferation of H322M and H460M2 tumor cells, induced
      strong down-modulation of IGF-1R as well as enhanced EGFR down-modulation
      compared to the parental EGFR antibody GA201 and were ADCC competent. The
      bispecific XGFR derivatives showed a strong format dependent influence of N- or C
      terminal heavy and light chain scFv attachment on ADCC activity and an increase
      in receptor downregulation over the parental combination in vitro. XGFR2 and
      XGFR4 were selected for in vivo evaluation and showed potent anti-tumoral
      efficacy comparable to the combination of monospecific IGF-1R and EGFR antibodies
      in subcutaneous BxPC3 and H322M xenograft models. In summary, we have managed to
      overcome issues of stability and productivity of bispecific antibodies,
      discovered important antibody fusion protein design related differences on ADCC
      activity and receptor downmodulation and show that IGF-1R-EGFR antibodies
      represent an attractive therapeutic strategy to simultaneously target two key
      components de-regulated in multiple cancer types, with the ultimate goal to avoid
      the formation of resistance to therapy.

PMID- 22464988
TI  - Posttranscriptional regulation of connexin-43 expression.
AB  - Posttranscriptional regulation of the biosynthesis of connexins, the building
      blocks of gap junctional channels, may occur by modulation of connexin mRNA
      stability and translation. To date, few RNA binding proteins and micro-RNAs
      (miRNAs) affecting connexin expression are known. Two examples of
      posttranscriptional regulatory processes resulting in the modulation of gap
      junctional intercellular communication are the stabilization of connexin-43 mRNA
      by the RNA binding protein HuR and the blocking effect of miRNAs miR-1 and -206
      on connexin-43 mRNA translation. These processes may be affected by stressful
      stimuli, such as by oxidative stress and environmental factors. Moreover,
      posttranscriptional regulatory circuits may be involved in the pathogenesis of
      disease and thus provide suitable targets for therapeutic approaches aiming at
      altering connexin expression.

PMID- 22464989
TI  - A novel activity for fungal nitronate monooxygenase: detoxification of the
      metabolic inhibitor propionate-3-nitronate.
AB  - Nitronate monooxygenase (NMO; E.C. 1.13.12.16) oxidizes alkyl nitronates to
      aldehydes and nitrite. Although the biochemistry of the enzyme from fungal
      sources has been studied extensively, the physiological role is unknown. The
      ability of NMO to detoxify propionate-3-nitronate was tested by measuring growth
      of recombinant Escherichia coli containing the gene encoding for the enzyme in
      either the absence or presence of the nitronate and its conjugate acid 3
      nitropropionate. The mixture propionate-3-nitronate/3-nitropropionate is toxic to
      E. coli cells lacking expression of NMO, but the toxicity is overcome through
      either induction of the gene for NMO or through addition of exogenous enzyme to
      the cultures. Both Williopsis saturnus and Neurospora crassa were able to grow in
      the presence of 0.4mM propionate-3-nitronate and 19.6mM 3-nitropropionate, while
      a knockout mutant of N. crassa lacking NMO was inhibited by concentrations of
      propionate-3-nitronate and 3-nitropropionate >0.3 and 600MUM, respectively. These
      results strongly support the conclusion that NMO functions to protect the fungi
      from the environmental occurrence of the metabolic toxin.

PMID- 22464990
TI  - Glutathione-mediated neuroprotection against methylmercury neurotoxicity in
      cortical culture is dependent on MRP1.
AB  - Methylmercury (MeHg) exposure at high concentrations poses significant neurotoxic
      threat to humans worldwide. The present study investigated the mechanisms of
      glutathione-mediated attenuation of MeHg neurotoxicity in primary cortical
      culture. MeHg (5 MUM) caused depletion of mono- and disulfide glutathione in
      neuronal, glial and mixed cultures. Supplementation with exogenous glutathione,
      specifically glutathione monoethyl ester (GSHME) protected against the MeHg
      induced neuronal death. MeHg caused increased reactive oxygen species (ROS)
      formation measured by dichlorodihydrofluorescein (DCF) fluorescence with an early
      increase at 30 min and a late increase at 6h. This oxidative stress was prevented
      by the presence of either GSHME or the free radical scavenger, trolox. While
      trolox was capable of quenching the ROS, it showed no neuroprotection. Exposure
      to MeHg at subtoxic concentrations (3 MUM) caused an increase in system x(c)(-)
      mediated (14)C-cystine uptake that was blocked by the protein synthesis
      inhibitor, cycloheximide (CHX). Interestingly, blockade of the early ROS burst
      prevented the functional upregulation of system x(c)(-). Inhibition of multidrug
      resistance protein-1 (MRP1) potentiated MeHg neurotoxicity and increased cellular
      MeHg. Taken together, these data suggest glutathione offers neuroprotection
      against MeHg toxicity in a manner dependent on MRP1-mediated efflux.

PMID- 22464991
TI  - Factors associated with non-completion in a double-blind randomized controlled
      trial of olanzapine plus sertraline versus olanzapine plus placebo for psychotic
      depression.
AB  - High rates of attrition have been reported in randomized controlled trials of
      patients with severe psychiatric illness, including psychotic depression (MDpsy).
      The purpose of this study is to examine factors associated with overall attrition
      and with subtypes of attrition in the Study of the Pharmacotherapy of Psychotic
      Depression (STOP-PD). Secondary analysis of data collected in a multi-site,
      randomized, placebo-controlled trial. Clinical services of academic hospitals.
      Participants comprised 259 persons with MDpsy, aged 18-93 years. The intervention
      consisted of the random allocation to 12 weeks of treatment of either olanzapine
      plus sertraline or olanzapine plus placebo. Demographic and clinical variables
      associated with overall non-completion and sub-types of non-completion of
      randomized treatment. One hundred and seventeen (45.2%) subjects did not complete
      12 weeks of randomized treatment. In a logistic regression analysis, inpatient
      entry status, olanzapine monotherapy, and higher cumulative medical burden were
      statistically significant independent predictors of overall non-completion. In a
      multinomial logistic regression model that examined predictors of subtypes of non
      completion, subjects who entered the study as an inpatient were less likely to
      complete because of inadequate efficacy as determined by the investigator, and
      older subjects were less likely to complete because of poorer tolerability.
      Subjects who were assigned to olanzapine monotherapy, younger subjects, and
      subjects who entered the study as inpatients were less likely to complete because
      of reasons other than efficacy or tolerability. Understanding factors that
      contribute to premature discontinuation in studies of MDpsy, and to the specific
      reasons for attrition, has the potential to improve the management of this
      disorder, as well as improve the design of future clinical trials of MDpsy.

PMID- 22464993
TI  - The role of imaging in staging and monitoring testicular cancer.
AB  - The prognosis for testicular cancer is excellent, with a 5-year survival rate
      greater than 95%. Patients affected can therefore expect to be cured after
      treatment. Successful treatment requires assessment of the condition at the
      various stages of its management. Imaging plays a major role in initial analysis
      of the lymphatic extension and in looking for metastases. It is essential for
      evaluating the response to treatment and during follow-up after treatment. CT is
      the most commonly used imaging method in this context, but the role of PET is
      currently developing. The purpose of this paper is to review the role of the
      imaging methods commonly used in the management of testicular cancer.

PMID- 22464992
TI  - Patients with functional psychoses show similar visual backward masking deficits.
AB  - Recent genetic, behavioral, and clinical studies suggest that functional
      psychoses (schizophrenia, bipolar disorder, schizoaffective disorder), previously
      thought to be distinct from each other, may belong to one continuum. The shine
      through masking paradigm is a potential endophenotype of schizophrenia with high
      sensitivity and specificity for discriminating between patients, their clinically
      unaffected relatives, and healthy controls. Hence, if schizophrenia, bipolar
      disorder and schizoaffective disorder belong to one common disease, strong
      masking deficits are expected to occur in all three diseases whereas no masking
      deficits are expected for abstinent alcoholic or depressive patients. Indeed, we
      found masking to be much stronger in psychotic patients compared to controls and
      to depressive patients and abstinent alcoholics, who performed on similar levels.

PMID- 22464994
TI  - Radiologically-guided thermal ablation of renal tumours.
AB  - Thermal ablation techniques for renal tumours have become the norm in surgically
      at-risk patients. These percutaneous treatments are locally effective,
      particularly for tumours measuring less than 4cm. Larger tumours may be treated
      by adapting the technique and strategy. Multidisciplinary discussion is essential
      before any decision, in order to decide on the most appropriate technique.
      Radiofrequency is simple, effective and inexpensive. Cryotherapy is more complex
      and should be preferred when the tumour is large or there is vascular or urinary
      tract contact. Microwaves can be used to treat larger tumours. Morbidity is low,
      but good knowledge of these techniques and of dissection is required to avoid
      injury to neighbouring digestive or urinary structures.

PMID- 22464995
TI  - Imaging techniques for local recurrence of prostate cancer: for whom, why and
      how?
AB  - Since there are salvage solutions, it is important to detect local recurrence of
      prostate cancer as early as possible. The first sign is "biochemical failure" in
      that the prostate specific antigen (PSA) concentration rises again. The
      definition of biochemical failure varies depending on the initial treatment: PSA
      greater than 0.2ng/mL after prostatectomy, nadir+2ng/mL after radiotherapy. There
      is no standardised definition of biochemical failure after cryotherapy, focused
      ultrasound, or brachytherapy. Magnetic resonance imaging (MRI) (particularly
      dynamic MRI) can detect local recurrence with good sensitivity. The role of
      spectroscopy is still under discussion. For the moment, ultrasound techniques are
      less effective than MRI.

PMID- 22464996
TI  - Tumour pathology of the bladder: the role of MRI.
AB  - Bladder cancer occurs frequently and is serious. Although ultrasound and CT
      examination are essential, magnetic resonance imaging is more effective for
      staging large tumours and in atypical cases, in particular submucosal lesions. CT
      and MRI are equally effective in examining the lymph nodes. The examination
      technique is simple. The prospects for using MRI, in particular with diffusion
      imaging, are being evaluated.

PMID- 22464997
TI  - Tumours of the bladder: what does the urologist expect from imaging?
AB  - Cancer of the bladder is the seventh most common of all cancers observed in
      France, and is the second urological cancer after prostate cancer. It is mainly
      related to nicotine addiction. When doing the initial tests, ultrasound
      examination of the bladder can enable the clinician to diagnose a polypoid tumour
      and thus avoid his having to organise diagnostic fibroscopy. When the bladder
      tumour infiltrates the detrusor muscle, the situation becomes life-threatening
      for the patient and radical treatment is envisaged. Uro-CT is the standard
      examination to characterise the lesion and describe its relationship with
      neighbouring organs. It is essential, and must be performed before endoscopic
      resection of the tumour, to be correctly interpreted. It is imperative for
      imaging to look for a synchronous lesion in the upper urinary tract (ureters,
      renal pelvis), because the presence of such a lesion changes the prognosis of the
      disease and the sequence of therapy, which is decided by the urologist in a
      multidisciplinary consultation.

PMID- 22464998
TI  - Diminution of hemoglobin-derived hemorphin: an underlying risk factor for
      cognitive deficit in diabetes.

PMID- 22465000
TI  - Control of ion transport by mitochondrion-rich chloride cells of eurythermic
      teleost fish: Cold shock vs. cold acclimation.
AB  - Seawater-acclimated eurythermic mummichogs (Fundulus heteroclitus L.) were
      acclimated to cold and warm conditions (5 and 20  degrees C, 4 weeks). Opercular
      epithelia (OE) from 20  degrees C-acclimated animals, containing numerous
      mitochondrion-rich chloride cells were mounted in Ussing-style membrane chambers,
      cooled to 16, 13, 10, 5 and 2.5  degrees C, then subjected to hypotonic shock
      that normally inhibits Cl(-) secretion (as short-circuit current, I(sc)). Cold
      exposure to 10  degrees C slowed Cl(-) secretion (Q(10)=1.62 +/- 0.204 95% CI)
      and OEs responded rapidly and reversibly to hypotonic shock, but below 8.0 
      degrees C a sharp decrease (Q(10)=5.63 +/- 0.736) occurred and the tissue was
      unresponsive to hypotonicity. By immunocytochemistry, Focal Adhesion Kinase (FAK)
      phosphorylated at tyrosine-407 (pY(407)) colocalized with CFTR in apical membrane
      and dephosphorylated with hypotonic shock at 20  degrees C but failed to
      dephosphorylate at 5  degrees C, while opercular epithelia from cold-acclimated
      fish at 5 and 20  degrees C responded normally to hypotonic shock. Cold-shock of
      warm-acclimated OEs also stimulated covering over of mitochondrion- rich cell
      apical crypts, detected by SEM. Cold-acclimation increased C18:1 and decreased
      C18:0 fatty acids in liver, indicating homeoviscous adaptation. Eurythermic fish
      acclimate osmoregulatory systems to cold by maintaining membrane fluidity and
      preserving complex transport regulation pathways.

PMID- 22465001
TI  - Micro and nanoparticle deposition in human nasal passage pre and post virtual
      maxillary sinus endoscopic surgery.
AB  - Realistic 3-D models of the human nasal passages were developed pre and post
      virtual uncinectomy and Middle Meatal Antrostomy. A 3-D computational domain was
      constructed by a series of coronal CT scan images from a healthy subject. Then a
      virtual uncinectomy intervention and maxillary antrostomy were performed on the
      left nasal passage by removing the uncinate process and exposing the maxillary
      sinus antrum. For several breathing rates corresponding to low or moderate
      activities, the airflows in the nasal passages were simulated numerically pre and
      post virtual routine maxillary sinus endoscopic surgery. The airflow distribution
      in the nasal airway, maxillary and frontal sinuses were analyzed and compared
      between pre and post surgery cases. A Lagrangian trajectory analysis approach was
      used for evaluating the path and deposition of microparticles in the nasal
      passages and maxillary sinuses. A diffusion model was used for nanoparticle
      transport and deposition analysis. The deposition rate of the inhaled micro and
      nanoparticles in the sinuses were evaluated and compared for pre and post
      operation conditions. The results showed that after maxillary sinus endoscopic
      surgery, the inhaled nano and microparticles can easily enter this sinus due to
      penetration of the airflow into the sinus cavity. This was in contrast to the
      preoperative condition in which almost no particles entered the sinuses. These
      results could be of importance for a better understanding of the effect of sinus
      endoscopic surgery on patient exposure to particulate pollution and inhalation
      drug delivery. The significantly higher airflow rate and particle deposition in
      the sinus could be a reason for the discomfort reported by some patient after
      maxillary sinus endoscopic surgery.

PMID- 22465002
TI  - Mechanisms-based classifications of musculoskeletal pain: part 2 of 3: symptoms
      and signs of peripheral neuropathic pain in patients with low back (+/- leg)
      pain.
AB  - As a mechanisms-based classification of pain 'peripheral neuropathic pain' (PNP)
      refers to pain arising from a primary lesion or dysfunction in the peripheral
      nervous system. Symptoms and signs associated with an assumed dominance of PNP in
      patients attending for physiotherapy have not been extensively studied. The
      purpose of this study was to identify symptoms and signs associated with a
      clinical classification of PNP in patients with low back (+/- leg) pain. Using a
      cross-sectional, between-subjects design; four hundred and sixty-four patients
      with low back (+/- leg) pain were assessed using a standardised assessment
      protocol. Patients' pain was assigned a mechanisms-based classification based on
      experienced clinical judgement. Clinicians then completed a clinical criteria
      checklist specifying the presence or absence of various clinical criteria. A
      binary logistic regression analysis with Bayesian model averaging identified a
      cluster of two symptoms and one sign predictive of PNP, including: 'Pain referred
      in a dermatomal or cutaneous distribution', 'History of nerve injury, pathology
      or mechanical compromise' and 'Pain/symptom provocation with mechanical/movement
      tests (e.g. Active/Passive, Neurodynamic) that move/load/compress neural tissue'.
      This cluster was found to have high levels of classification accuracy
      (sensitivity 86.3%, 95% CI: 78.0-92.3; specificity 96.0%, 95% CI: 93.4-97.8;
      diagnostic odds ratio 150.9, 95% CI: 69.4-328.1). Pattern recognition of this
      empirically-derived cluster of symptoms and signs may help clinicians identify an
      assumed dominance of PNP mechanisms in patients with low back pain disorders in a
      way that might usefully inform subsequent patient management.

PMID- 22465003
TI  - Do patients with elderly-onset rheumatoid arthritis have severe functional
      disability?
AB  - OBJECTIVE: To identify the clinical features of elderly-onset rheumatoid
      arthritis (EORA) and their impact on disease outcome. METHODS: A total of 3169
      rheumatoid arthritis (RA) patients were recruited as part of the Korean
      Observational Study Network for Arthritis, the nationwide cohort of South Korea.
      Patients were stratified according to age at disease onset: <40 years (younger
      age-onset RA, n = 1167), between the ages of 40 and 59 (middle-aged-onset RA, n =
      1516), and >=60 years (EORA, n = 486). To evaluate the significance of
      differences in clinical features among these 3 groups, we performed analysis of
      variance (anova) and the chi(2) test. We used multivariable logistic regression
      analysis to examine the association of onset age with functional disability
      measured with Health Assessment Questionnaire-Disability Index (HAQDI). RESULTS:
      EORA patients were associated with high HAQDI (>=1) in bivariable analysis [odds
      ratio (OR) 1.36, confidence interval (CI) 1.04-1.77]. However, in multivariable
      analysis, not elderly onset but patients' age, female gender, high disease
      activity, disease duration over 10 years, and comorbidity with cardiovascular
      disease were associated with high HAQDI. Only in a predefined subgroup with
      disease duration <10 years, elderly onset was an independent influencing factor
      for the functional disability of RA patients (OR 3.04, CI 1.85-5.67: disease
      duration of <5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years).
      CONCLUSIONS: Disease onset in older age was associated independently with
      functional disability of RA patients who have relatively short disease duration.

PMID- 22465004
TI  - Beetroot juice protects against N-nitrosodiethylamine-induced liver injury in
      rats.
AB  - Red beetroot, a common ingredient of diet, is a rich source of a specific class
      of antioxidants, betalains. Our previous studies have shown the protective role
      of beetroot juice against carcinogen induced oxidative stress in rats. The aim of
      this study was to examine the effect of long term feeding (28 days) with beetroot
      juice on phase I and phase II enzymes, DNA damage and liver injury induced by
      hepatocarcinogenic N-nitrosodiethylamine (NDEA). Long term feeding with beetroot
      juice decreased the activities of enzymatic markers of cytochrome P450,
      CYP1A1/1A2 and CYP2E1. NDEA treatment also reduced the activities of these
      enzymes, but increased the activity of CYP2B. Moreover, combined treatment with
      beetroot juice and NDEA enhanced significantly CYP2B only. Modulation of P450
      enzyme activities was accompanied by changes in the relevant proteins levels.
      Increased level and activity of NQO1 was the most significant change among phase
      II enzymes. Beetroot juice reduced the DNA damage increased as the result of NDEA
      treatment, as well as the biomarkers of liver injury. Collectively, these results
      confirm the protective effect of beetroot juice against oxidative damage shown in
      our previous studies and indicate that metabolic alterations induced by beetroot
      feeding may protect against liver damage.

PMID- 22465005
TI  - Study of mycotoxin calibration approaches on the example of trichothecenes
      analysis from flour.
AB  - The aim of this study was to evaluate the applicability of different calibration
      approaches in trichothecenes analysis from wheat flour. Concretely eight
      trichothecenes (five type B trichothecenes and three type A trichothecenes) were
      analyzed by matrix solid-phase dispersion (MSPD) and liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). In the first set of experiments the presence of
      matrix effects was evaluated; values ranged between 59% and 79%. In the second
      set of experiments, solutions to compensate these signal suppressions were
      examined. Different calibration methods showed to tackle matrix effects obtaining
      values between 69% and 85% for external matrix matched calibration and values
      from 76% to 111% and from 78% to 108% by analog and deuterated internal standard
      calibrations, respectively. Trueness of the method was studied using quality
      control material and certificated reference material (DON 1062 +/- 110 MUg kg(
      1)). The values were compared by matrix-matched, analog internal standard
      (deepoxydeoxynivalenol (DOM-1)) and deuterated internal standard (DON-d(1)).

PMID- 22465006
TI  - A structurally novel hemopexin fold protein of rice plays role in chlorophyll
      degradation.
AB  - Proteins containing hemopexin fold domain are suggested to have diverse functions
      in various living organisms. In order to investigate the structure and function
      of this type of protein in rice plant (Oryza sativa), the gene encoding a
      hemopexin fold protein (OsHFP) was cloned, analyzed in silico and characterized.
      Molecular modeling revealed that the OsHFP is closely related to other hemopexin
      fold proteins, but is unique with a cylindrical central tunnel as well as
      extended N- and C-terminal domains. The recombinant OsHFP was found to bind
      hemin, the oxidized form of heme in vitro. The expression of the single copy
      OsHFP gene was detected in rice flower buds. Heterologous expression of OsHFP in
      green leaf tissues resulted in chlorophyll degradation; however, stable
      expression of OsHFP was observed in transgenic hairy roots, a non-green tissue.
      The possible role of OsHFP in regulating programmed cell death in anther green
      tissues of rice is proposed.

PMID- 22465007
TI  - A new mitochondrial pH biosensor for quantitative assessment of pancreatic beta
      cell function.
AB  - Mitochondrial pH is a key determinant of mitochondrial energy metabolism. We have
      developed a new fluorescence-based ratiometric pH biosensor using a chloride
      insensitive and hydrogen-sensitive probe for direct, quantitative and bleaching
      free measurement in a living cell. Fusing this biosensor with a mitochondrial
      localization signal (MTpHGV) allowed us to determine mitochondrial pH. This new
      system was applied to measure mitochondrial pH in pancreatic beta-cells, in which
      mitochondrial function plays a pivotal role in insulin secretion. Rat INS1 cells
      and mouse MIN6 cells are transfected with MTpHGV stably to monitor mitochondrial
      pH. While carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment rapidly
      decreased mitochondrial pH in cultured rat MTpHGV-INS-1 cells, MTpHGV-MIN6 cells
      showed a rapid increase. These data suggest that MTpHGV probe exist in matrix
      side in INS-1 cells, but on the outer side of mitochondrial inner membrane in
      MIN6 cells. Moreover, while MTpHGV-INS-1 cells showed a rapid increase of pH by
      glucose stimulation, mitochondrial pH decreased quickly by glucose stimulation in
      all MTpHGV-MIN6 cells examined and recovered smoothly. Perfusion study of glucose
      load in MTpHGV-MIN6 cells under aminooxyacetate (AOA) or 100MUM diazoxide showed
      that this mitochondrial pH acidification was dependent on nicotinamide adenine
      dinucleotide (NADH) shuttle, but independent from KATP channel. This new system
      for measuring mitochondrial pH is sensitive across the range of physiologic
      conditions and may be a useful tool for evaluating mitochondrial function in
      living cells.

PMID- 22465008
TI  - How do tumor stem cells actively escape from host immunosurveillance?
AB  - Tumor stem cells (TSCs) are considered as the "seeds" in tumor development,
      metastasis and recurrence. Despite the various immunosurveillance mechanisms in
      the host, TSCs may possess the phenotypic and functional properties to evade host
      immunosurveillance and immune-mediated rejection in immunologically intact
      individuals. The mechanisms of TSC recognition and their consequent destruction
      are actively disturbed by various processes, including altered immunogenicity of
      TSCs, production of TSC-derived regulatory molecules, and interaction of TSCs
      with tumor-infiltrating immune cells. In addition to these TSC-mediated
      mechanisms, the diverse mesenchymal cells and cytokines in the tumor
      microenvironment are contribute to TSC immune escape. Recent mechanistic studies
      provide a more comprehensive understanding of TSCs in the biology, prevention,
      and therapy of solid tumors. This review will focus on the latest findings for
      mechanisms underlying TSCs' escape from the attack of immune system.

PMID- 22465010
TI  - Reversible induction of PARP1 degradation by p53-inducible cis-imidazoline
      compounds.
AB  - PARP1 is an important enzyme involved in various patho-physiological phenomena
      such as ischemia/reperfusion (I/R) injury, which occurs when blood flow is
      restored after cerebral infarction, myocardial infarction and transplantation of
      various organs. I/R-induced PARP1 over-activation is mediated by production of
      reactive oxygen species and is involved in NF-kappaB transactivation. For these
      reasons, PARP1 is an attractive target for strategies to protect against I/R
      injury. We previously reported that an MDM2 inhibitor Nutlin3a, a cis-imidazoline
      compound, induces PARP1 degradation in a p53 and proteasome-dependent manner. In
      this study, we evaluated the effect of Nutlin3a analogs, Nutlin3b and Caylin2, on
      PARP1 degradation. Like Nutlin3a, Caylin2, but not Nutlin3b, induced PARP1
      degradation in both 3T3-L1 and 3T3-F442A. This result occurred almost in parallel
      with p53 accumulation. Furthermore Caylin2-induced PARP1 degradation was not
      observed in p53 deficient mouse embryonic fibroblasts or in the presence of the
      proteasome inhibitor MG132. These results suggest that Caylin2 induces PARP1
      degradation by the same mechanism as Nutlin3a. Finally, we showed that Nutlin3a
      or Caylin2 treatment induces reversible PARP1 down-regulation without an
      inflammatory response. For protection against I/R injury, our results support the
      usability of the p53 inducible cis-imidazoline compounds, Nutlin3a and its
      analogs, as PARP1 inhibitors.

PMID- 22465011
TI  - MiR-499 induces cardiac differentiation of rat mesenchymal stem cells through
      wnt/beta-catenin signaling pathway.
AB  - OBJECTIVE: To test the hypothesis that over-expressing miR-499 in rat bone marrow
      derived mesenchymal stem cells (BM-MSCs) induces them to differentiate into
      cardiomyocyte-like cells through the wnt/beta-catenin signaling pathway. METHODS:
      Rat BM-MSCs were infected with lentiviral vectors bearing miR-499. The expression
      of cardiac-specific markers, NKx2.5, GATA4, MEF2C, and cTnI in these cells were
      examined by rtPCR or Western blot analysis and the activity of the wnt/beta
      catenin signaling pathway was evaluated by measuring the phosphorylation status
      of beta-catenin. RESULTS: Over-expression of miR-499 in rat BM-MSCs increased the
      expression of cardiac-specific genes, such as NKx2.5, GATA4, MEF2C, and cTnI and
      decreased the ratio of phosphorylated/dephosphorylated beta-catenin in the
      wnt/beta-catenin signaling pathway, thus activating the pathway. Knocking down
      the expression of Dvl, an adaptor molecule in the wnt/beta-catenin signaling,
      partially blocked the role of the miR-499 and decreased those cardiac-specific
      genes. CONCLUSION: Over-expression of miR-499 in rat BM-MSCs induces them toward
      cardiac differentiation through the activating the wnt/beta-catenin signal
      pathway.

PMID- 22465009
TI  - Ligand structural motifs can decouple glucocorticoid receptor transcriptional
      activation from target promoter occupancy.
AB  - Glucocorticoid (GC) induction of the tyrosine aminotransferase (TAT) gene by the
      glucocorticoid receptor (GR) is a classic model used to investigate steroid
      regulated gene expression. Classic studies analyzing GC-induction of the TAT gene
      demonstrated that despite having very high affinity for GR, some steroids cannot
      induce maximal TAT enzyme activity, but the molecular basis for this phenomenon
      is unknown. Here, we used RT-PCR and chromatin immunoprecipitation to determine
      TAT mRNA accumulation and GR recruitment to the TAT promoter (TAT-GRE) in rat
      hepatoma cells induced by seven GR ligands: dexamethasone (DEX), cortisol (CRT),
      corticosterone (CCS), 11-deoxycorticosterone (DOC), aldosterone (ALD),
      progesterone (PRG) and 17-hydroxyprogesterone (17P). As expected, DEX, CRT, CCS
      and ALD all induced both TAT mRNA and GR recruitment to the TAT-GRE, while PRG
      and 17P did not. However, while DOC could not induce significant TAT mRNA, it did
      induce robust GR occupancy of the TAT-GRE. DOC also induced recruitment of the
      histone acetyltransferase p300 to the TAT-GRE as efficiently as DEX. These DOC
      induced effects recapitulated at another GR target gene (sulfonyltransferase
      1A1), and DOC also failed to promote the multiple changes in gene expression
      required for glucocorticoid-dependent 3T3-L1 adipocyte differentiation.
      Structural simulations and protease sensitivity assays suggest that DOC and DEX
      induce different conformations in GR. Thus, although steroids that bind GR with
      high affinity can induce GR and p300 occupancy of target promoters, they may not
      induce a conformation of GR capable of activating transcription.

PMID- 22465012
TI  - Role of bone marrow cells in the development of pancreatic fibrosis in a rat
      model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet.
AB  - Bone marrow cell (BMC)-derived myofibroblast-like cells have been reported in
      various organs, including the pancreas. However, the contribution of these cells
      to pancreatic fibrosis has not been fully discussed. The present study examined
      the possible involvement of pancreatic stellate cells (PSCs) originating from
      BMCs in the development of pancreatic fibrosis in a clinically relevant rat model
      of acute pancreatitis induced by a choline-deficient/ethionine-supplemented (CDE)
      diet. BMCs from female transgenic mice ubiquitously expressing green fluorescent
      protein (GFP) were transplanted into lethally irradiated male rats. Once
      chimerism was established, acute pancreatitis was induced by a CDE diet.
      Chronological changes in the number of PSCs originating from the donor BMCs were
      examined using double immunofluorescence for GFP and markers for PSCs, such as
      desmin and alpha smooth muscle actin (alphaSMA), 1, 3 and 8 weeks after the
      initiation of CDE feeding. We also used immunohistochemical staining to evaluate
      whether the PSCs from the BMCs produce growth factors, such as platelet-derived
      growth factor (PDGF) and transforming growth factor (TGF) beta1. The percentage
      of BMC-derived activated PSCs increased significantly, peaking after 1 week of
      CDE treatment (accounting for 23.3+/-0.9% of the total population of activated
      PSCs) and then decreasing. These cells produced both PDGF and TGFbeta1 during the
      early stage of pancreatic fibrosis. Our results suggest that PSCs originating
      from BMCs contribute mainly to the early stage of pancreatic injury, at least in
      part, by producing growth factors in a rat CDE diet-induced pancreatitis model.

PMID- 22465013
TI  - Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family
      proteins.
AB  - Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid
      compound isolated from Curcuma xanthorrhiza. Previously, we have reported that
      xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by
      inducing apoptotic cell death via caspase activation. Here, we attempt to further
      elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated
      HepG2 cells as observed by scanning electron microscopy was accompanied by
      truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X(L)
      expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken
      together, these results suggest xanthorrhizol as a potent antiproliferative agent
      on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed
      that xanthorrhizol could be used as an anti-liver cancer drug for future studies.

PMID- 22465014
TI  - Over-expression of human clusterin increases stress resistance and extends
      lifespan in Drosophila melanogaster.
AB  - Clusterin is a disulfide-linked heterodimeric glycoprotein that has been
      implicated in a variety of biological processes. Its expression has been shown to
      be elevated during cellular senescence and normal aging, but it is uncertain
      whether clusterin protects against aging or whether its expression is a
      consequence of aging. To investigate the functions of clusterin during organismal
      aging, we established transgenic Drosophila alleles to induce the expression of
      the secretory form of human clusterin (hClu(S)) using the Gal4/UAS system.
      hClu(S) protein (~60 kDa) was detected in both adult homogenates and larval
      hemolymphs of flies ubiquitously overexpressing hClu(S) (da-Gal4>UAS-hClu(S)) and
      in motoneurons (D42-Gal4>UAS-hClu(S)). Interestingly, the mean lifespans of these
      hClu(S)-overexpressing flies were significantly greater than those of control
      flies that exhibited no hClu(S) induction. hClu(S)-overexpressing flies also
      showed significantly greater tolerance to heat shock, wet starvation, and
      oxidative stress. Furthermore, amounts of reactive oxygen species (ROS) in whole
      bodies were significantly lower in hClu(S)-overexpressing flies. In addition,
      clusterin was found to prevent the inactivation of glutamine synthetase (GS) by
      metal-catalyzed oxidation (MCO) in vitro, and this protection was only supported
      by thiol-reducing equivalents, such as, DTT or GSH, and not by ascorbate (a non
      thiol MCO system). Furthermore, this protection against GS inactivation by
      clusterin was abolished by reacting clusterin with N-ethylmaleimide, a sulfhydryl
      group-modifying agent. Taken together, these results suggest that a disulfide
      linked form of clusterin functions as an antioxidant protein via its cysteine
      sulfhydryl groups to reduce ROS levels and delay the organismal aging in fruit
      flies.

PMID- 22465015
TI  - Gene expression profile in the liver of Rana catesbeiana tadpoles exposed to low
      temperature in the presence of thyroid hormone.
AB  - Amphibian metamorphosis, which is controlled by thyroid hormone (TH), is highly
      temperature-sensitive. Using real-time PCR, we investigated the gene expression
      profile in the liver of Rana catesbeiana tadpoles kept at 28 and 4  degrees C and
      treated with 5 nM 3,3',5-triiodothyronine (T3). Out of the 48 genes tested, 12
      were up-regulated at 4  degrees C in T3-treated or untreated tadpoles. These
      included genes involved in energy metabolism, transcription, and translation.
      Four TH-response genes, including TH receptor beta (TRbeta) gene, showed no
      response to T3 at 4  degrees C. Deiodinase III was the only gene down-regulated
      at 4  degrees C. Chromatin immunoprecipitation assays showed that CCAAT/enhancer
      binding protein 2 gene activation by cold exposure was associated with an
      increase in the acetylation of histone H3 at lysine 9, whereas TRbeta gene
      activation by T3 at 28  degrees C was associated with an increase in the
      methylation of histone H3 at lysine 36 with no T3-dependent changes in
      methylation states on cold exposure. Our results suggest that the transfer of TH
      signal to chromatin modifications on a primary early TH response gene was
      specifically blocked by exposure to cold.

PMID- 22465016
TI  - Symptoms tell it all: a systematic review of the value of symptom assessment to
      predict survival in advanced cancer patients.
AB  - PURPOSE: To determine the prognostic meaning of symptoms in patients with
      advanced cancer. DESIGN: Medline, Embase, Cochrane and Cinahl databases were
      systematically explored. The predicting symptoms were also evaluated in the three
      stages of palliative care: disease-directed palliation, symptom-oriented
      palliation and palliation in the terminal stage. RESULTS: Out of 3167 papers,
      forty-four papers satisfied all criteria. Confusion, anorexia, fatigue, cachexia,
      weight loss, cognitive impairment, drowsiness, dyspnea, dysphagia, dry mouth and
      depressed mood were associated with survival in >= 50% of the studies evaluating
      these symptoms. Multivariate analysis showed confusion, anorexia, fatigue,
      cachexia, weight loss, dyspnea and dysphagia as independent prognostic factors in
      30-56% of the studies. In the stage of disease-directed palliation anorexia,
      cachexia, weight loss, dysphagia and pain and in the stage of symptom-oriented
      palliation confusion, fatigue, cachexia, weight loss, dyspnea, dysphagia and
      nausea were shown to be independent predictors of survival in >30% of the
      studies. CONCLUSION: Symptoms with independent predictive value are confusion,
      anorexia, fatigue, cachexia, weight loss, dyspnea and dysphagia. New insights are
      added by the variance between the three palliative stages.

PMID- 22465017
TI  - The UniProtKB/Swiss-Prot Tox-Prot program: A central hub of integrated venom
      protein data.
AB  - Animal toxins are of interest to a wide range of scientists, due to their
      numerous applications in pharmacology, neurology, hematology, medicine, and drug
      research. This, and to a lesser extent the development of new performing tools in
      transcriptomics and proteomics, has led to an increase in toxin discovery. In
      this context, providing publicly available data on animal toxins has become
      essential. The UniProtKB/Swiss-Prot Tox-Prot program
      (http://www.uniprot.org/program/Toxins) plays a crucial role by providing such an
      access to venom protein sequences and functions from all venomous species. This
      program has up to now curated more than 5000 venom proteins to the high-quality
      standards of UniProtKB/Swiss-Prot (release 2012_02). Proteins targeted by these
      toxins are also available in the knowledgebase. This paper describes in details
      the type of information provided by UniProtKB/Swiss-Prot for toxins, as well as
      the structured format of the knowledgebase.

PMID- 22465018
TI  - Influence of Crassostrea gigas (Thunberg) sexual maturation stage and ploidy on
      uptake of paralytic phycotoxins.
AB  - The purpose of this study was to assess paralytic phycotoxin uptake in diploid
      and triploid oysters at two stages of their sexual cycle corresponding to their
      status in early summer (June) and winter (November). Samples of diploid and
      triploid oysters were exposed to a toxic culture of Alexandrium minutum for 4
      days in each season. No significant differences in filtration or clearance rates
      were observed during either November or June experiments. When diploid oysters
      were at resting stage (November), toxin uptake showed no significant difference
      between the ploidy classes. In contrast, when the diploid oysters were at the
      peak of their sexual maturation (June), the triploid oysters were seen to
      accumulate almost double the amount of paralytic toxins as the diploid ones.

PMID- 22465019
TI  - Occurrences of flesh flies (Diptera: Sarcophagidae) on human cadavers in
      Switzerland, and their importance as forensic indicators.
AB  - From 1993 to 2008, criminal investigations were conducted in the western part of
      Switzerland with special attention to blowfly and flesh fly species in order to
      estimate the post-mortem interval when requested by the police authorities. Flesh
      flies were found in only 33 cases out of 160. Five species of the genus
      Sarcophaga were identified (S. africa, S. argyrostoma, S. caerulescens, S.
      similis and S. sp.). The main species found on corpses (larval stage) was S.
      argyrostoma. The thermal constant (K) calculated for this species in Switzerland
      is 380.6 +/- 16.3 (mean +/- S.D.) degree-days. With the exception of S.
      caerulescens, found three times in the larval stage on corpses, the three other
      species are of minor forensic importance. S. argyrostoma is found during summer
      and indoors. This species colonises dead bodies, usually the same day as blowfly
      species, and it could be used to estimate the post-mortem interval. Other species
      are discussed in the light of current knowledge on their biology and ecology. It
      is recommended that voucher material be deposited in a museum, allowing further
      studies by relevant specialists, thereby helping investigators and avoiding
      misidentifications.

PMID- 22465020
TI  - Leveraging metabolomics for functional investigations in sequenced marine
      diatoms.
AB  - Recent years have witnessed the genomic decoding of a wide range of
      photosynthetic organisms from the model plant Arabidopsis thaliana and the
      complex genomes of important crop species to single-celled marine phytoplankton.
      The comparative sequencing of green, red and brown algae has provided
      considerable insight into a number of important questions concerning their
      evolution, physiology and metabolism. The combinatorial application of
      metabolomics has further deepened our understanding both of the function of
      individual genes and of metabolic processes. Here we discuss the power of
      utilising metabolomics in conjunction with sequencing data to gain greater
      insight into the metabolic hierarchies underpinning the function of individual
      organisms, using unicellular marine diatoms as a case study to exemplify the
      advantages of this approach.

PMID- 22465021
TI  - Novel endocrine aspects of prostate cancer.

PMID- 22465022
TI  - Rotary catalysis of the stator ring of F(1)-ATPase.
AB  - F(1)-ATPase is a rotary motor protein in which 3 catalytic beta-subunits in a
      stator alpha(3)beta(3) ring undergo unidirectional and cooperative conformational
      changes to rotate the rotor gamma-subunit upon adenosine triphosphate hydrolysis.
      The prevailing view of the mechanism behind this rotary catalysis elevated the
      gamma-subunit as a "dictator" completely controlling the chemical and
      conformational states of the 3 catalytic beta-subunits. However, our recent
      observations using high-speed atomic force microscopy clearly revealed that the 3
      beta-subunits undergo cyclic conformational changes even in the absence of the
      rotor gamma-subunit, thus dethroning it from its dictatorial position. Here, we
      introduce our results in detail and discuss the possible operating principle
      behind the F(1)-ATPase, along with structurally related hexameric ATPases, also
      mentioning the possibility of generating hybrid nanomotors. This article is part
      of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

PMID- 22465024
TI  - Chloroplast biogenesis - correlation between structure and function.
AB  - Chloroplast biogenesis is a multistage process leading to fully differentiated
      and functionally mature plastids. Complex analysis of chloroplast biogenesis was
      performed on the structural and functional level of its organization during the
      photoperiodic plant growth after initial growth of seedlings in the darkness. We
      correlated, at the same time intervals, the structure of etioplasts transforming
      into mature chloroplasts with the changes in the photosynthetic protein levels
      (selected core and antenna proteins of PSI and PSII) and with the function of the
      photosynthetic apparatus in two plant species: bean (Phaseolus vulgaris L.) and
      pea (Pisum sativum L). We selected these plant species since we demonstrated
      previously that the mature chloroplasts differ in the thylakoid organization. We
      showed that the protein biosynthesis as well as photosynthetic complexes
      formation proceeds gradually in both plants in spite of periods of darkness. We
      found that both steady structural differentiation of the bean chloroplast and
      reformation of prolamellar bodies in pea were accompanied by a gradual increase
      of the photochemical activity in both species. This article is part of a Special
      Issue entitled: Photosynthesis Research for Sustainability: from Natural to
      Artificial.

PMID- 22465023
TI  - Inter-monomer electron transfer is too slow to compete with monomeric turnover in
      bc(1) complex.
AB  - The homodimeric bc(1) complexes are membrane proteins essential in respiration
      and photosynthesis. The ~11A distance between the two b(L)-hemes of the dimer
      opens the possibility of electron transfer between them, but contradictory
      reports make such inter-monomer electron transfer controversial. We have
      constructed in Rhodobacter sphaeroides a heterodimeric expression system similar
      to those used before, in which the bc(1) complex can be mutated differentially in
      the two copies of cyt b to test for inter-monomer electron transfer, but found
      that genetic recombination by cross-over then occurs to produce wild-type
      homodimer. Selection pressure under photosynthetic growth always favored the
      homodimer over heterodimeric variants enforcing inter-monomer electron transfer,
      showing that the latter are not competitive. These results, together with kinetic
      analysis of myxothiazol titrations, demonstrate that inter-monomer electron
      transfer does not occur at rates competitive with monomeric turnover. We examine
      the results from other groups interpreted as demonstrating rapid inter-monomer
      electron transfer, conclude that similar mechanisms are likely to be in play, and
      suggest that such claims might need to be re-examined.

PMID- 22465025
TI  - Restricted capacity for PSI-dependent cyclic electron flow in DeltapetE mutant
      compromises the ability for acclimation to iron stress in Synechococcus sp. PCC
      7942 cells.
AB  - Exposure of wild type (WT) and plastocyanin coding petE gene deficient mutant
      (DeltapetE) of Synechococcus cells to low iron growth conditions was accompanied
      by similar iron-stress induced blue-shift of the main red Chl a absorption peak
      and a gradual decrease of the Phc/Chl ratio, although DeltapetE mutant was more
      sensitive when exposed to iron deficient conditions. Despite comparable iron
      stress induced phenotypic changes, the inactivation of petE gene expression was
      accompanied with a significant reduction of the growth rates compared to WT
      cells. To examine the photosynthetic electron fluxes in vivo, far-red light
      induced P700 redox state transients at 820nm of WT and DeltapetE mutant cells
      grown under iron sufficient and iron deficient conditions were compared. The
      extent of the absorbance change (DeltaA(820)/A(820)) used for quantitative
      estimation of photooxidizable P700(+) indicated a 2-fold lower level of P700(+)
      in DeltapetE compared to WT cells under control conditions. This was accompanied
      by a 2-fold slower re-reduction rate of P700(+) in the DeltapetE indicating a
      lower capacity for cyclic electron flow around PSI in the cells lacking
      plastocyanin. Thermoluminescence (TL) measurements did not reveal significant
      differences in PSII photochemistry between control WT and DeltapetE cells.
      However, exposure to iron stress induced a 4.5 times lower level of P700(+), 2
      fold faster re-reduction rate of P700(+) and a temperature shift of the TL peak
      corresponding to S(2)/S(3)Q(B)(-) charge recombination in WT cells. In contrast,
      the iron-stressed DeltapetE mutant exhibited only a 40% decrease of P700(+) and
      no significant temperature shift in S(2)/S(3)Q(B)(-) charge recombination. The
      role of mobile electron carriers in modulating the photosynthetic electron fluxes
      and physiological acclimation of cyanobacteria to low iron conditions is
      discussed. This article is part of a Special Issue entitled: Photosynthesis
      Research for Sustainability: from Natural to Artificial.

PMID- 22465026
TI  - Metal cations modulate the bacteriochlorophyll-protein interaction in the light
      harvesting 1 core complex from Thermochromatium tepidum.
AB  - The light-harvesting 1 reaction center (LH1-RC) complex from Thermochromatium
      (Tch.) tepidum exhibits unusual Q(y) absorption by LH1 bacteriochlorophyll-a
      (BChl-a) molecules at 915nm, and the transition energy is finely modulated by the
      binding of metal cations to the LH1 polypeptides. Here, we demonstrate the metal
      dependent interactions between BChl-a and the polypeptides within the intact LH1
      RC complexes by near-infrared Raman spectroscopy. The wild-type LH1-RC (B915)
      exhibited Raman bands for the C3-acetyl and C13-keto CO stretching modes at 1637
      and 1675cm(-1), respectively. The corresponding bands appeared at 1643 and
      1673cm(-1) when Ca(2+) was biosynthetically replaced with Sr(2+) (B888) or at
      1647 and 1669cm(-1) in the mesophilic counterpart, Allochromatium vinosum. These
      results indicate the significant difference in the BChl-polypeptide interactions
      between B915 and B888 and between B915 and the mesophilic counterpart. The
      removal of the original metal cations from B915 and B888 resulted in marked band
      shifts of the C3-acetyl/C13-carbonyl nuCO modes to ~1645/~1670cm(-1), supporting
      a model in which the metal cations are involved in the fine-tuning of the
      hydrogen bonding between the BChl-a and LH1-polypeptides. Interestingly, the
      interaction modes were almost identical between the Ca(2+)-depleted B915 and
      Sr(2+)-depleted B888 and between B915 and Ca(2+)-substituted B888, despite the
      significant differences in their LH1 Q(y) peak positions and the denaturing
      temperatures, as revealed by differential scanning calorimetry. These results
      suggest that not only the BChl-polypeptide interactions but some structural
      origin may be involved in the unusual Q(y) red-shift and the enhanced thermal
      stability of the LH1-RC complexes from Tch. tepidum.

PMID- 22465027
TI  - Role of zinc in catalytic activity of carbonic anhydrase IX.
AB  - The carbonic anhydrases (CAs) in the alpha class are zinc-dependent
      metalloenzymes. Previous studies have reported that recombinant forms of carbonic
      anhydrase IX (CAIX), a membrane-bound form of CA expressed in solid tumors,
      appear to be activated by low levels of zinc independent of its well-studied role
      at the catalytic site. In this study, we sought to determine if CAIX is
      stimulated by zinc in its native environment. MDA-MB-231 breast cancer cells
      express CAIX in response to hypoxia. We compared CAIX activity associated with
      membrane ghosts isolated from hypoxic cells with that in intact hypoxic cells. We
      measured CA activity directly using (18)O exchange from (13)CO(2) into water
      determined by membrane inlet mass spectrometry. In membrane ghosts, there was
      little effect of zinc at low concentrations on CAIX activity, although at high
      concentration zinc was inhibitory. In intact cells, zinc had no significant
      effect on CAIX activity. This suggests that there is an appreciable decrease in
      sensitivity to zinc when CAIX is in its natural membrane milieu compared to the
      purified forms.

PMID- 22465028
TI  - Prevention mechanisms of glucose intolerance and obesity by cacao liquor
      procyanidin extract in high-fat diet-fed C57BL/6 mice.
AB  - In this study, we investigated whether cacao liquor procyanidin (CLPr) extract,
      which consists of 4.3% catechin, 6.1% epicatechin, 39.4% procyanidins and others,
      ameliorated hyperglycemia and obesity in C57BL/6 mice fed a control or high-fat
      diet for 13 weeks. CLPr suppressed high-fat diet-induced hyperglycemia, glucose
      intolerance and fat accumulation in white adipose tissue. CLPr also promoted
      translocation of glucose transporter 4 (GLUT4) and phosphorylation of AMP
      activated protein kinase alpha (AMPKalpha) in the plasma membrane of skeletal
      muscle and brown adipose tissue. Phosphorylation of AMPKalpha was also enhanced
      in the liver and white adipose tissue. CLPr up-regulated the gene and protein
      expression levels of uncoupling protein (UCP)-1 in brown adipose tissue and UCP-3
      in skeletal muscle. These results indicate that CLPr is a beneficial food
      material for the prevention of hyperglycemia and obesity. Activation of
      AMPKalpha, translocation of GLUT4 and up-regulation of UCP expression in skeletal
      muscle and adipose tissue are involved in the molecular mechanisms by which CLPr
      prevents hyperglycemia and obesity.

PMID- 22465029
TI  - Engineering of an industrial polyoxin producer for the rational production of
      hybrid peptidyl nucleoside antibiotics.
AB  - Polyoxins and nikkomycins are potent antifungal peptidyl nucleoside antibiotics,
      which inhibit fungal cell wall biosynthesis. They consist of a nucleoside core
      and one or two independent peptidyl moieties attached to the core at different
      sites. Making mutations and introducing heterologous genes into an industrial
      Streptomyces aureochromogenes polyoxin producer, resulted in the production of
      four polyoxin-nikkomycin hybrid antibiotics designated as polyoxin N and nikkoxin
      B-D, whose structures were confirmed using high resolution MS and NMR. Two of the
      hybrid antibiotics, polyoxin N and nikkoxin D, were significantly more potent
      against some human or plant fungal pathogens than their parents. The data
      provides an example for rational generation of novel peptidyl nucleoside
      antibiotics in an industrial producer.

PMID- 22465031
TI  - Midterm survival in patients treated for atrial fibrillation: a propensity
      matched comparison to patients without a history of atrial fibrillation.
AB  - OBJECTIVE: Patients undergoing cardiac surgery with a history of untreated atrial
      fibrillation have reduced survival compared with similar patients without atrial
      fibrillation. We sought to compare the midterm survival of patients who received
      concomitant surgical ablation treatment for atrial fibrillation (atrial
      fibrillation ablated) with that of matched patients without a history of atrial
      fibrillation (no atrial fibrillation). METHODS: We evaluated 3262 consecutive
      patients (813 [25%] with atrial fibrillation and 2449 [75%] without preoperative
      atrial fibrillation) undergoing cardiac surgery at a single institution from
      April 2004 to April 2009. Of patients with atrial fibrillation, 565 (70%) were
      treated with a concomitant surgical ablation procedure. Propensity scores were
      calculated on the basis of 37 known preoperative risk factors and yielded 744
      patients. Midterm survival was compared between patients with atrial fibrillation
      ablation (n = 372) and patients without atrial fibrillation (n = 372). Survival
      was also compared between patients with successful vs unsuccessful ablation, and
      a matched analysis was performed at 1 year between the 2 groups. RESULTS: Mean
      follow-up was 2.7 +/- 1.6 years. Patients without atrial fibrillation and
      patients with treated atrial fibrillation had similar early 30-day mortality
      (1.2% vs 0.3%, P = .37) and overall mortality rates (11.6% vs 9.4%, P = .344),
      respectively. Survival analysis showed no differences at 1, 3, and 5 years
      between the 2 groups (log-rank P = .22). At last follow-up, 78% of treated
      patients were free of atrial fibrillation. At 1 year, 68% of patients were free
      of atrial fibrillation and antiarrhythmic medication. Freedom from atrial
      fibrillation and antiarrhythmic medication at 1 year predicted improved midterm
      survival (P = .03) compared with patients in atrial fibrillation or taking
      antiarrhythmic medication. Propensity-matched analysis after 1 year demonstrated
      improved survival for patients who were successfully treated (P = .016).
      CONCLUSIONS: Patients undergoing surgical treatment of atrial fibrillation had
      survival similar to that of patients without a history of atrial fibrillation.
      Those with successful sinus restoration had improved survival compared with those
      who were treated but remained in atrial fibrillation.

PMID- 22465032
TI  - Water mobility, denaturation and the glass transition in proteins.
AB  - A quantitative mechanism is presented that links protein denaturation and the
      protein-water glass transition through an energy criterion for the onset of
      mobility of strong protein-water bonds. Differences in the zero point vibrational
      energy in the ordered and disordered bonded states allow direct prediction of the
      two transition temperatures. While the onset of water mobility induces the same
      change in heat capacity for both transitions, the order-disorder transition of
      denaturation also predicts the observed excess enthalpy gain. The kinetics of the
      water and protein components through the glass transition are predicted and
      compared with dielectric spectroscopy observations. The energetic approach
      provides a consistent mechanism for processes such as refolding and aggregation
      of proteins involved in protein maintenance and adaptability, as the
      conformational constraints of strong water-amide bonds are lost with increased
      molecular mobility. Moreover, we suggest that the ordered state of peptide-water
      bonds is induced at the point of protein synthesis and could play a key role in
      the function of proteins through the enhancement of electronic activity by
      ferroelectric domains in the protein hydration shell, which is lost upon
      denaturation.

PMID- 22465033
TI  - Lysosomal di-N-acetylchitobiase-deficient mouse tissues accumulate Man2GlcNAc2
      and Man3GlcNAc2.
AB  - Most lysosomal storage diseases are caused by defects in genes encoding for
      acidic hydrolases. Deficiency of an enzyme involved in the catabolic pathway of N
      linked glycans leads to the accumulation of the respective substrate and
      consequently to the onset of a specific storage disorder. Di-N-acetylchitobiase
      and core specific alpha1-6mannosidase represent the only exception. In fact, to
      date no lysosomal disease has been correlated to the deficiency of these enzymes.
      We generated di-N-acetylchitobiase-deficient mice by gene targeting of the Ctbs
      gene in murine embryonic stem cells. Accumulation of Man2GlcNAc2 and Man3GlcNAc2
      was evaluated in all analyzed tissues and the tetrasaccharide was detected in
      urines. Multilamellar inclusion bodies reminiscent of polar lipids were present
      in epithelia of a scattered subset of proximal tubules in the kidney. Less
      constantly, enlarged Kupffer cells were observed in liver, filled with phagocytic
      material resembling partly digested red blood cells. These findings confirm an
      important role for lysosomal di-N-acetylchitobiase in glycans degradation and
      suggest that its deficiency could be the cause of a not yet described lysosomal
      storage disease.

PMID- 22465034
TI  - Adaptation of respiratory chain biogenesis to cytochrome c oxidase deficiency
      caused by SURF1 gene mutations.
AB  - The loss of Surf1 protein leads to a severe COX deficiency manifested as a fatal
      neurodegenerative disorder, the Leigh syndrome (LS(COX)). Surf1 appears to be
      involved in the early step of COX assembly but its function remains unknown. The
      aim of the study was to find out how SURF1 gene mutations influence expression of
      OXPHOS and other pro-mitochondrial genes and to further characterize the altered
      COX assembly. Analysis of fibroblast cell lines from 9 patients with SURF1
      mutations revealed a 70% decrease of the COX complex content to be associated
      with 32-54% upregulation of respiratory chain complexes I, III and V and
      accumulation of Cox5a subunit. Whole genome expression profiling showed a general
      decrease of transcriptional activity in LS(COX) cells and indicated that the
      adaptive changes in OXPHOS complexes are due to a posttranscriptional
      compensatory mechanism. Electrophoretic and WB analysis showed that in
      mitochondria of LS(COX) cells compared to controls, the assembled COX is present
      entirely in a supercomplex form, as I-III2-IV supercomplex but not as larger
      supercomplexes. The lack of COX also caused an accumulation of I-III2
      supercomplex. The accumulated Cox5a was mainly present as a free subunit. We have
      found out that the major COX assembly subcomplexes accumulated due to SURF1
      mutations range in size between approximately 85-140kDa. In addition to the
      originally proposed S2 intermediate they might also represent Cox1-containing
      complexes lacking other COX subunits. Unlike the assembled COX, subcomplexes are
      unable to associate with complexes I and III.

PMID- 22465035
TI  - Quantitative magnetic analysis reveals ferritin-like iron as the most predominant
      iron-containing species in the murine Hfe-haemochromatosis.
AB  - Quantitative analysis of the temperature dependent AC magnetic susceptibility of
      freeze-dried mouse tissues from an Hfe hereditary haemochromatosis disease model
      indicates that iron predominantly appears biomineralised, like in the ferritin
      cores, in the liver, the spleen and duodenum. The distribution of the amount of
      ferritin-like iron between genders and genotypes coincides with that of elemental
      iron and nonheme iron. Importantly, the so-called paramagnetic iron, a quantity
      also determined from the magnetic data and indicative of nonmineralised iron
      forms, appears only marginally increased when iron overload takes place.

PMID- 22465037
TI  - Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic
      strategies.
AB  - The utility of anthracycline antineoplastic agents in the clinic is compromised
      by the risk of cardiotoxicity. It has been calculated that approximately 10% of
      patients treated with doxorubicin or its derivatives will develop cardiac
      complications up to 10 years after the cessation of chemotherapy. Oxidative
      stress has been established as the primary cause of cardiotoxicity. However,
      interventions reducing oxidative stress have not been successful at reducing the
      incidence of cardiotoxicity in patients treated with doxorubicin. New insights
      into the cardiomyocyte response to oxidative stress demonstrate that underlying
      differences between in vitro and in vivo toxicities may modulate the response to
      superoxide radicals and related compounds. This has led to potentially new uses
      for pre-existing drugs and new avenues of exploration to find better
      pharmacotherapies and interventions for the prevention of cardiotoxicity.
      However, much work still must be done to validate the clinical utility of these
      new approaches and proposed mechanisms. In this review, the authors have reviewed
      the molecular mechanisms of the pathogenesis of acute and chronic doxorubicin
      induced cardiotoxicity and propose potential pharmacological interventions and
      treatment options to prevent or reverse this specific type of heart failure.

PMID- 22465039
TI  - LR-PED rule: low risk pulmonary embolism decision rule - a new decision score for
      low risk pulmonary embolism.
AB  - INTRODUCTION: When accurately diagnosed, non-massive Pulmonary embolism (PE) has
      a low mortality rate. However, some patients initially considered to be low risk
      show progressive deterioration. This research aims at developing a preliminary
      score that allows detection of low risk patients potentially eligible for
      outpatient treatment. MATERIALS AND METHODS: Retrospective cohort study involving
      142 asymptomatic/mildly symptomatic and hemodynamically stable patients with PE
      and no clinical/echocardiographic signs of right ventricular dysfunction.
      Collected data: risk factors, analytic/gasometric parameters, admission
      echocardiogram, thoracic CT angiography. Patients followed for 6months. Primary
      endpoint: 1-month all-cause mortality. Secondary endpoints: Intrahospital and 6
      month all-cause mortality. A score designed for identification of very low risk
      patients eligible for outpatient treatment was developed and its prognostic
      accuracy compared to that of the Geneva and simplified PESI models. RESULTS: A
      score for predicting 1-month mortality (Low Risk Pulmonary Embolism Decision [LR
      PED] rule) was obtained using Binary Logistic Regression, including: age, atrial
      fibrillation at admission, previous heart failure, admission heart rate,
      creatinine, glycaemia, troponin I and C-reactive protein at admission. ROC curve
      analysis assessed its overall accuracy for predicting 1-month, intrahospital and
      6-month mortality (AUC=0.756, 0.763 and 0.854, respectively). Compared to Geneva
      and simplified PESI, the LR-PED rule showed higher sensitivity and negative
      predictive value for the detection of the lowest risk patients. The net
      reclassification improvement index revealed significant successful upward risk
      reclassification by the LR-PED model of patients reaching primary or secondary
      outcomes. CONCLUSIONS: LR-PED rule seems more attractive than Geneva or
      simplified PESI in its ability to identify patients at very low mortality risk
      who would be potentially eligible for outpatient treatment. Prospective
      validation of this score in larger cohorts is mandatory before its potential
      implementation.

PMID- 22465040
TI  - Protection of lung epithelial cells from protease-mediated injury by trappin-2
      A62L, an engineered inhibitor of neutrophil serine proteases.
AB  - Neutrophil serine proteases (NSPs), including elastase, proteinase 3 and
      cathepsin G, play critical roles in the pathogenesis of chronic inflammatory lung
      diseases. The release of excess NSPs leads to the destruction of lung tissue and
      an overexuberant, sustained inflammatory response. Antiproteases could be
      valuable tools for controlling these NSP-mediated inflammatory events. We have
      examined the capacity of trappin-2 A62L, a potent engineered inhibitor of all
      three NSPs, to protect human lung A549 epithelial cells from the deleterious
      effects of NSPs. Trappin-2 A62L, significantly inhibited the detachment of A549
      cells and the degradation of the tight-junction proteins, E-cadherin, beta
      catenin and ZO-1, induced by each individual NSP and by activated neutrophils.
      Trappin-2 A62L also decreased the release of the pro-inflammatory cytokines IL-6
      and IL-8 from A549 cells that had been stimulated with elastase or LPS. Trappin-2
      A62D/M63L, a trappin-2 variant that has no antiprotease activity, has similar
      properties, suggesting that the anti-inflammatory action of trappin-2 is
      independent of its antiprotease activity. Interestingly, we present evidence that
      trappin-2 A62L, as well as wild-type trappin-2, enter A549 cells and move rapidly
      to the cytoplasm and nucleus, where they are likely to exert their anti
      inflammatory effects. We have also demonstrated that trappin-2 A62L inhibits the
      early apoptosis of A549 cells mediated by NSPs. Thus, our data indicate that
      trappin-2 A62L is a powerful anti-protease and anti-inflammatory agent that could
      be used to develop a treatment for patients with inflammatory lung diseases.

PMID- 22465038
TI  - Notch signaling and cardiac repair.
AB  - Notch signaling is critical for proper heart development and recently has been
      reported to participate in adult cardiac repair. Notch resides at the cell
      surface as a single pass transmembrane receptor, transits through the cytoplasm
      following activation, and acts as a transcription factor upon entering the
      nucleus. This dynamic and widespread cellular distribution allows for potential
      interactions with many signaling and binding partners. Notch displays temporal as
      well as spatial versatility, acting as a strong developmental signal, controlling
      cell fate determination and lineage commitment, and playing a pivotal role in
      embryonic and adult stem cell proliferation and differentiation. This review
      serves as an update of recent literature addressing Notch signaling in the heart,
      with attention to findings from noncardiac research that provide clues for
      further interpretation of how the Notch pathway influences cardiac biology.
      Specific areas of focus include Notch signaling in adult myocardium following
      pathologic injury, the role of Notch in cardiac progenitor cells with respect to
      differentiation and cardiac repair, crosstalk between Notch and other cardiac
      signaling pathways, and emerging aspects of noncanonical Notch signaling in
      heart.

PMID- 22465042
TI  - Unifying concepts and mechanisms in the specificity of plant-enemy interactions.
AB  - Host ranges are commonly quantified to classify herbivores and plant pathogens as
      either generalists or specialists. Here, we summarize patterns and mechanisms in
      the interactions of plants with these enemies along different axes of
      specificity. We highlight the many dimensions within which plant enemies can
      specify and consider the underlying ecological, evolutionary and molecular
      mechanisms. Host resistance traits and enemy effectors emerge as central players
      determining host utilization and thus host range. Finally, we review approaches
      to studying the causes and consequences of variation in the specificity of plant
      enemy interactions. Knowledge of the molecular mechanisms that determine host
      range is required to understand host shifts, and evolutionary transitions among
      specialist and generalist strategies, and to predict potential host ranges of
      pathogens and herbivores.

PMID- 22465041
TI  - Fusicoccanes: diterpenes with surprising biological functions.
AB  - Fusicoccin is the best-studied member of a class of diterpenes sharing a 5-8-5
      ring structure, called fusicoccanes. Fusicoccin was and still is a 'tool in plant
      physiology', targeting the main engine of plasma membrane transport, the P-type
      H(+)-ATPase, assisted by members of the 14-3-3 family. The key position of 14-3-3
      proteins in cell biology, combined with a broader specificity of other
      fusicoccanes as shown by crystallography studies, make fusicoccanes a versatile
      tool in plant and animal biology. In this review, we examine recent evidence that
      fusicoccanes act on animal cells, describe the discovery of the fungal
      biosynthetic pathway and emphasize that lower (liverworts) and higher plants
      produce fusicoccanes with intriguing biological activities.

PMID- 22465043
TI  - Respiratory distress syndrome (RDS) in premature infants is underscored by the
      magnitude of Th1 cytokine polarization.
AB  - Respiratory distress syndrome (RDS) is a common problem and the leading cause of
      death in premature infants (PI). The introduction of surfactant treatment for RDS
      management has lowered mortality and morbidity; nevertheless, some neonates do
      not improve and are at increased risk of pulmonary hemorrhage. Inflammation, not
      only local but also systemic, seems to play an important role in the pathogenesis
      of RDS. To determine whether cytokine patterns characterize RDS and its outcome,
      we measured type-1 (IL-2, TNF-alpha, IFN-gamma, IL-6) and type-2 (IL-4, IL-5, IL
      10, TGF-beta1) serum cytokines of 47 PI with established RDS and a control group
      of 30 healthy, appropriate for gestational age, full-term neonates. Cord blood
      samples were obtained at the time of delivery from PI and controls. Venous blood
      samples were collected from PI who received surfactant treatment and/or developed
      pulmonary hemorrhage. Significantly elevated cord blood cytokine levels were
      observed in PI at time of delivery, compared to controls, except for IL-5 and TNF
      alpha levels that were within control range. The type-1/type-2 cytokine ratio was
      significantly increased in PI vs controls. Neonates who developed pulmonary
      hemorrhage between 2 and 3 days of life and/or died, presented the strongest Th1
      and type-1 cytokine polarization that was mainly due to increased IFN-gamma and
      TNF-alpha, and decreased TGF-beta1. The majority of these PI were female with
      very low gestational age. Overall, PI with RDS present a Th1/type-1 cytokine
      polarization, which persists irrespective of the treatment provided, and is
      amplified when complications appear. Th1 polarization is associated with poor
      prognosis.

PMID- 22465044
TI  - The T29C polymorphism of the transforming growth factor-beta1 (TGF-beta1) gene is
      associated with genetic susceptibility to acute coronary syndrome in Mexican
      patients.
AB  - Inflammation plays an essential role in the development and progression of
      atherosclerotic lesions, and plaque disruption. The TGF-beta1 plays an important
      role in the anti-inflammatory process. The aim of the present study was to
      evaluate the role of TGF-beta1 gene polymorphisms as susceptibility markers for
      acute coronary syndrome (ACS). Two polymorphisms (TGF-beta -509T>C and TGF-beta
      T29C) of the TGF-beta gene were analyzed by 5' exonuclease TaqMan genotyping
      assays in a group of 426 patients with coronary acute syndrome and 551 healthy
      unrelated controls. A significant difference was observed in the distribution of
      TGF-beta T29C polymorphism between ACS patients and healthy controls (P<10(-3)).
      According to the co-dominant model, individuals with the TGF-beta 29 TT genotype
      have a 2.5-fold increased risk of developing ACS (P<10(-3)). Multiple logistic
      analysis showed that the largest risk factor for developing ACS was given by
      smoking habit, diabetes, hypertension, dyslipidemia, and the TGF-beta1 29 TT
      genotype. The analysis of linkage disequilibrium showed one haplotype (TT) with
      increased frequency and one haplotype (CC) with decreased frequency in ACS
      patients when compared to healthy controls. The results suggest that TGF-beta1
      T29C gene polymorphism could be involved in the risk of developing ACS in Mexican
      individuals.

PMID- 22465045
TI  - Attentional control deficits in trait anxiety: why you see them and why you
      don't.
AB  - Attentional Control Theory (ACT; Eysenck et al., 2007; Derakshan and Eysenck,
      2009) posits that trait anxiety interferes with the inhibition, shifting and
      updating processes of working memory. Consequently, high anxious individuals are
      predicted to perform worse on cognitively demanding tasks requiring efficient
      cognitive processing. Whilst a growing number of studies have provided support
      for this view, the possible underlying mechanisms of this deficiency are far less
      understood. In particular, there is conflicting neuroscientific evidence with
      some work showing associations between anxiety and increased neural activity over
      frontal areas, while others report reduced activity. We review recent evidence
      that has helped elucidate the cognitive hallmarks of trait anxiety, and suggest
      how previous discrepancies can be accommodated within ACT's prediction that
      reduced cognitive efficiency may be ameliorated by strategies such as
      compensatory effort. Finally, we discuss if ACT's distinction on efficiency and
      effectiveness can be applied to threat-related processing, often shown to
      additively override attentional control in anxiety.

PMID- 22465046
TI  - A rare case of pericarditis, complication of infliximab treatment for Crohn's
      disease.

PMID- 22465036
TI  - Charcot-Marie-Tooth disease and intracellular traffic.
AB  - Mutations of genes whose primary function is the regulation of membrane traffic
      are increasingly being identified as the underlying causes of various important
      human disorders. Intriguingly, mutations in ubiquitously expressed membrane
      traffic genes often lead to cell type- or organ-specific disorders. This is
      particularly true for neuronal diseases, identifying the nervous system as the
      most sensitive tissue to alterations of membrane traffic. Charcot-Marie-Tooth
      (CMT) disease is one of the most common inherited peripheral neuropathies. It is
      also known as hereditary motor and sensory neuropathy (HMSN), which comprises a
      group of disorders specifically affecting peripheral nerves. This peripheral
      neuropathy, highly heterogeneous both clinically and genetically, is
      characterized by a slowly progressive degeneration of the muscle of the foot,
      lower leg, hand and forearm, accompanied by sensory loss in the toes, fingers and
      limbs. More than 30 genes have been identified as targets of mutations that cause
      CMT neuropathy. A number of these genes encode proteins directly or indirectly
      involved in the regulation of intracellular traffic. Indeed, the list of genes
      linked to CMT disease includes genes important for vesicle formation,
      phosphoinositide metabolism, lysosomal degradation, mitochondrial fission and
      fusion, and also genes encoding endosomal and cytoskeletal proteins. This review
      focuses on the link between intracellular transport and CMT disease, highlighting
      the molecular mechanisms that underlie the different forms of this peripheral
      neuropathy and discussing the pathophysiological impact of membrane transport
      genetic defects as well as possible future ways to counteract these defects.

PMID- 22465047
TI  - Growth hormone treatment for sustained pain reduction and improvement in quality
      of life in severe fibromyalgia.
AB  - Functional defects in growth hormone (GH) secretion and its efficacy as a
      complementary treatment have been suggested for fibromyalgia. This study
      investigated the efficacy and safety of low-dose GH as an add-on therapy in
      patients with both severe FM and low insulin-like growth factor 1 levels. A total
      of 120 patients were enrolled in a multicenter, placebo-controlled study for 18
      months. They were randomly assigned to receive either 0.006 mg/kg/day of GH
      subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind
      phase). The placebo arm was switched to GH treatment from month 6 to month 12
      (open phase), and a follow-up period after GH discontinuation was performed until
      month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake
      inhibitors, opioids, and amitriptyline) was maintained throughout the study.
      Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ)
      with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue
      scale (VAS) were assessed at different time points. At the end of the study, 53%
      of group A patients obtained fewer than 11 positive tender points, vs 33% of
      group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS
      (P<.05). Group A patients showed significantly improved FIQ scores (P=.01)
      compared with group B. Although GH discontinuation worsened all scores in both
      groups during follow-up, impairment in pain perception was less pronounced in the
      GH-treated group (P=.05). In this largest and longest placebo-controlled trial
      performed in FM (NCT00933686), addition of GH to the standard treatment is
      effective in reducing pain, showing sustained action over time.

PMID- 22465048
TI  - The combined use of a biosurfactant and an enzyme preparation to treat an
      effluent with a high fat content.
AB  - The combined use of a rhamnolipid biosurfactant produced by Pseudomonas
      aeruginosa and an enzyme pool produced by solid-state fermentation with
      Penicillium simplicissimum using babassu cake as culture medium in the anaerobic
      treatment of an effluent with a high fat content from a poultry processing plant
      was evaluated. Central composite rotatable design was used to evaluate the enzyme
      pool and biosurfactant concentrations and the treatment temperature of the
      effluent containing about 2400 mg oil and grease per liter. The combination that
      yielded the highest specific methane production was 0.19% (w/v) enzyme pool and
      114 mg/L biosurfactant at 33  degrees C. It could therefore be concluded that the
      combined use of a rhamnolipid biosurfactant with an enzyme preparation obtained
      from solid-state fermentation may enhance methane production and enable the use
      of anaerobic technology in this sector, eliminating the need for physicochemical
      processes or the addition of costly commercial enzymes.

PMID- 22465049
TI  - A high sensitive voltammetric sensor for qualitative and quantitative
      determination of phenobarbital as an antiepileptic drug in presence of
      acetaminophen.
AB  - For the first time, the catalytic activity of phenobarbital (PB) in presence of
      acetaminophen (AC) was studied at the surface of modified electrode which
      prepared by incorporation of multi-walled carbon nanotube (MWCNT) and Pt
      nanoparticles into a paste matrix. Preparation of this electrode was very simple
      and modified electrode showed an excellent character for electrocatalytic
      oxidization of acetaminophen and phenobarbital. Using differential pulse
      voltammetry (DPV), a highly selective and simultaneous determination of AC and PB
      has been explored at the modified electrode. Differential pulse voltammetry peak
      currents of AC and PB increased linearly with their concentrations at the ranges
      of 0.5-100 MUM and 0.4-60 MUM, respectively. Also, the detection limits for AC
      and PB were 0.17 MUM and 0.1 MUM, respectively. The method has been found
      selective and successfully implemented for the determination of AC and PB in
      human urine and pharmaceutical samples using standard addition method. The
      electrode exhibited an efficient catalytic response with good reproducibility and
      stability.

PMID- 22465050
TI  - Memory formation, consolidation and transformation.
AB  - Memory formation is a highly dynamic process. In this review we discuss
      traditional views of memory and offer some ideas about the nature of memory
      formation and transformation. We argue that memory traces are transformed over
      time in a number of ways, but that understanding these transformations requires
      careful analysis of the various representations and linkages that result from an
      experience. These transformations can involve: (1) the selective strengthening of
      only some, but not all, traces as a function of synaptic rescaling, or some other
      process that can result in selective survival of some traces; (2) the integration
      (or assimilation) of new information into existing knowledge stores; (3) the
      establishment of new linkages within existing knowledge stores; and (4) the up
      dating of an existing episodic memory. We relate these ideas to our own work on
      reconsolidation to provide some grounding to our speculations that we hope will
      spark some new thinking in an area that is in need of transformation.

PMID- 22465052
TI  - A novel obatoclax derivative, SC-2001, induces apoptosis in hepatocellular
      carcinoma cells through SHP-1-dependent STAT3 inactivation.
AB  - We investigated the effects of a novel compound, SC-2001, on hepatocellular
      carcinoma (HCC). SC-2001, which is structurally related to the Mcl-1 inhibitor
      obatoclax, showed better antitumor effects than obatoclax in HCC cell lines,
      including HepG2, PLC5 and Huh-7. Like obatoclax, SC-2001 inhibited the protein
      protein interactions between Mcl-1 and Bak. However, SC-2001 downregulated the
      protein levels of Mcl-1 by reducing its transcription whereas obatoclax had no
      significant effect on Mcl-1 expression. As Mcl-1 is regulated by signal
      transducers and activators of transcription 3 (STAT3), we found that SC-2001
      downregulated the phosphorylation of STAT3 (Tyr 705) and subsequently inhibited
      transcriptional activities of STAT3 in a dose-dependent manner. In addition to
      Mcl-1, STAT3-regulated proteins, including survivin and cyclin D1, were also
      repressed by SC-2001. Notably, SC-2001 reduced IL-6-induced STAT3 activation in
      HepG2 and PLC5 cells. Ectopic expression of STAT3 abolished the prominent
      apoptotic death in SC-2001-treated PLC5 cells, indicating that STAT3 is
      indispensable in mediating the effects of SC-2001. Importantly, SC-2001 enhanced
      the expression of SHP1, a negative regulator of STAT3. Inhibition of SHP-1 by
      either specific inhibitor or small interference RNA reduced the apoptotic effects
      of SC-2001, indicating that SHP-1 plays a key role in mediating SC2001-induced
      cell death. SC-2001 enhanced the activity of SHP-1 in all tested HCC cells
      including HepG2, PLC5 and Huh-7. Finally, SC-2001 reduced PLC5 tumor growth,
      downregulated p-STAT3 and upregulated SHP-1 expression and activity in vivo. In
      conclusion, our results suggest that SC-2001 induces apoptosis in HCC, and that
      this effect is mediated through SHP-1-dependent STAT3 inactivation.

PMID- 22465053
TI  - [Poorer diabetes control among the immigrant population than among the
      autochthonous population].
AB  - INTRODUCTION: Ethnic differences are known to exist in the prevalence of
      diabetes, but little is known about possible differences in the degree of
      diabetes control among ethnic groups. The aim of this study was to determine
      whether there are differences in diabetes detection and control between
      immigrants and the autochthonous population in our health region. METHODS: We
      performed a cross-sectional, observational, population-based study of all
      patients diagnosed with diabetes mellitus type 2 registered and treated in 2010.
      We analyzed diabetes quality indicators and used multivariate logistic regression
      models adjusted for age, sex and number of visits. The adjustment method was
      forced and the absence of collinearity was identified through the ROC curve and
      Hosmer and Lemeshow's test. RESULTS: There were 77,999 autochthonous patients
      (6,846 diabetics) and 30,748 immigrant patients (415 diabetics). A total of 8.78%
      of the autochthonous patients were diabetic versus 1.35% of immigrants (p
      <0.001). HbA1c <7.5% was found in 68.04% of the native population compared with
      54.76% of immigrants. The probability of achieving optimal HbA1c control was 27%
      lower in immigrants (adjusted OR=0.73), while the probability of achieving good
      HbA1c control was 30% lower in the immigrant cohort. The model showed moderate
      discrimination (ROC =0.65 and Hosmer and Lemeshow's contrast, p>0.05).
      CONCLUSIONS: Diabetes control and quality indicators are poorer in some immigrant
      groups.

PMID- 22465054
TI  - Mercury levels in feathers of Magellanic penguins.
AB  - Feathers are useful to determine mercury (Hg) contamination. We evaluated the
      mercury concentration in feathers of Magellanic penguins (Spheniscus
      magellanicus) age 1.5 years to 25 years at Punta Tombo, Argentina before and
      during their molt. Mercury ranged between <1.4 and 367 ng/g dry weight, with
      three extreme high values (8996 ng/g, 3011 ng/g and 1340 ng/g) all in young
      adults. The median concentration was lowest for juveniles and significantly
      higher for adults but with high variation among older adults. Males and females
      had similar mercury loads. Compared with other penguin species, concentrations in
      Magellanic penguins were low. Mercury levels for Magellanic penguins in the
      Southwest Atlantic for older adults averaged 206+/-98 ng/g, and serve as a
      baseline for biomonitoring and/or ecotoxicological studies.

PMID- 22465055
TI  - Trace metal concentrations in southern right whale (Eubalaena australis) at
      Peninsula Valdes, Argentina.
AB  - The presence of essential (Fe, Mn, Zn, Cu, Ni and Al) and non-essential trace
      metals (Cd and Pb) was tested in liver (N=26) and kidney (N=42) from dead
      Southern Right Whale (SRW--Eubalaena australis) calves found beached in Peninsula
      Valdes, Argentina. Essential metals were detected in all samples, particularly in
      hepatic tissue; though Ni and Al were accumulated mainly in the kidney. Cd and Pb
      were not detected in any samples. Sex and length of calves did not influence
      metal levels found, nor did the geographic location of carcasses. Our findings
      for essential metals were similar to those reported for mysticetes in other parts
      of the world. Except for a previous report on one SRW calf, this is the first
      data on trace metals for this species in Patagonia. This information is vital for
      SRW management considering increasing human pressures impacting their feeding and
      breeding grounds.

PMID- 22465056
TI  - The trawling ban in Hong Kong's inshore waters--a round of applause and a plea to
      learn from others' mistakes.

PMID- 22465051
TI  - Creatine metabolism and psychiatric disorders: Does creatine supplementation have
      therapeutic value?
AB  - Athletes, body builders, and military personnel use dietary creatine as an
      ergogenic aid to boost physical performance in sports involving short bursts of
      high-intensity muscle activity. Lesser known is the essential role creatine, a
      natural regulator of energy homeostasis, plays in brain function and development.
      Creatine supplementation has shown promise as a safe, effective, and tolerable
      adjunct to medication for the treatment of brain-related disorders linked with
      dysfunctional energy metabolism, such as Huntington's Disease and Parkinson's
      Disease. Impairments in creatine metabolism have also been implicated in the
      pathogenesis of psychiatric disorders, leaving clinicians, researchers and
      patients alike wondering if dietary creatine has therapeutic value for treating
      mental illness. The present review summarizes the neurobiology of the creatine
      phosphocreatine circuit and its relation to psychological stress, schizophrenia,
      mood and anxiety disorders. While present knowledge of the role of creatine in
      cognitive and emotional processing is in its infancy, further research on this
      endogenous metabolite has the potential to advance our understanding of the
      biological bases of psychopathology and improve current therapeutic strategies.

PMID- 22465057
TI  - Uncertainty analysis along the ecological quality status of water bodies: the
      response of the Posidonia oceanica multivariate index (POMI) in three
      Mediterranean regions.
AB  - Uncertainty analyses allow the identification and quantification of the factors
      that contribute to the potential misclassification of the ecological status of
      water bodies, helping to improve the sampling design used in monitoring. Here we
      used a Posidonia oceanica multivariate index (POMI) bio-monitoring dataset
      covering a total of 81 sites distributed throughout 28 water bodies from the
      coast of Catalonia, Balearic Islands and Croatia to determine the levels of
      uncertainty associated with each region and how they change according to the
      quality status of water bodies. Overall, variability among sites (meadows) within
      water bodies was the factor that generated the greatest risk of misclassification
      among the three regions, within which the Balearic Islands had the lowest
      uncertainty, followed by Croatia and Catalonia. When water bodies classified in
      good/high quality were separated from those in moderate/poor status classes, we
      found that the latter displayed higher levels of uncertainty than the former.

PMID- 22465058
TI  - [Fetal Leptotrichia goodfellowii bacteremia].

PMID- 22465059
TI  - [Rhinocerebral mucormycosis].

PMID- 22465061
TI  - Novel antithrombotic agents for atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is estimated
      that 1 in 4 individuals aged 40 years or above will develop at least 1 episode of
      AF during their lifetime. Stroke is a leading cause of serious, long-term
      disability and death, and a major socioeconomic burden in developed countries.
      The major risk factor for thromboembolic stroke is AF. Oral antithrombotic
      treatment for AF patients has been limited to vitamin K antagonists for more than
      60 years. Treatment with warfarin can reduce, but fails to abolish thromboembolic
      stroke associated with AF. Despite anticoagulation, patients with AF are at
      increased stroke risk. Furthermore, warfarin has important limitations namely,
      the limited time in therapeutic range, the need for INR monitoring, risk of major
      bleeding including stroke, and drug interactions. Recently there have been very
      exciting and important new advances in thromboprophylaxis for AF. Novel oral
      agents have been developed and evaluated clinically. These include direct
      thrombin inhibitors (dabigatran etexilate), oral selective factor Xa inhibitors
      (rivaroxaban, apixaban and edoxaban) and PAR-1 inhibitors (vorapaxar and
      atopaxar). Some of the new drugs have demonstrated promising results in the
      clinical studies, they are convenient in use and do not require monitoring. The
      downsides are lack of antidotes or specific blood assays to monitor the
      anticoagulant effect. This review evaluates traditional and novel approaches to
      thromboprophylaxis in patients with AF.

PMID- 22465062
TI  - Spray congealed lipid microparticles with high protein loading: preparation and
      solid state characterisation.
AB  - The spray-congealing technique, a solvent-free drug encapsulation process, was
      successfully employed to obtain lipid-based particulate systems with high (10-20%
      w/w) protein loading. Bovine serum albumin (BSA) was utilised as model protein
      and three low melting lipids (glyceryl palmitostearate, trimirystin and
      tristearin) were employed as carriers. BSA-loaded lipid microparticles were
      characterised in terms of particle size, morphology and drug loading. The results
      showed that the microparticles exhibited a spherical shape, mean diameter in the
      range 150-300 MUm and an encapsulation efficiency higher than 90%. Possible
      changes in the protein structure as a result of the manufacturing process was
      then investigated for the first time using UV spectrophotometry in fourth
      derivative mode and FT-Raman spectroscopy. The results suggested that the
      structural integrity of the protein was maintained within the particles. Thermal
      analysis indicated that the effect of protein on the thermal properties of the
      carriers could be detected. Spray-congealing could thus be considered a suitable
      technique to produce highly BSA-loaded microparticles preserving the structure of
      the protein.

PMID- 22465060
TI  - Functional consequences of repeated organophosphate exposure: potential non
      cholinergic mechanisms.
AB  - The class of chemicals known as the "organophosphates" (OPs) comprises many of
      the most common agricultural and commercial pesticides that are used worldwide as
      well as the highly toxic chemical warfare agents. The mechanism of the acute
      toxicity of OPs in both target and non-target organisms is primarily attributed
      to inhibitory actions on various forms of cholinesterase leading to excessive
      peripheral and central cholinergic activity. However, there is now substantial
      evidence that this canonical (cholinesterase-based) mechanism cannot alone
      account for the wide-variety of adverse consequences of OP exposure that have
      been described, especially those associated with repeated exposures to levels
      that produce no overt signs of acute toxicity. This type of exposure has been
      associated with prolonged impairments in attention, memory, and other domains of
      cognition, as well as chronic illnesses where these symptoms are manifested
      (e.g., Gulf War Illness, Alzheimer's disease). Due to their highly reactive
      nature, it is not surprising that OPs might alter the function of a number of
      enzymes and proteins (in addition to cholinesterase). However, the wide variety
      of long-term neuropsychiatric symptoms that have been associated with OPs
      suggests that some basic or fundamental neuronal process was adversely affected
      during the exposure period. The purpose of this review is to discuss several non
      cholinesterase targets of OPs that might affect such fundamental processes and
      includes cytoskeletal and motor proteins involved in axonal transport,
      neurotrophins and their receptors, and mitochondria (especially their morphology
      and movement in axons). Potential therapeutic implications of these OP
      interactions are also discussed.

PMID- 22465063
TI  - Pharmacological effects of CS-0777, a selective sphingosine 1-phosphate receptor
      1 modulator: results from a 12-week, open-label pilot study in multiple sclerosis
      patients.
AB  - CS-0777 is a selective sphingosine 1-phosphate receptor-1 modulator under
      investigation for treatment of multiple sclerosis (MS). We conducted an open
      label, pilot study in 25 MS patients to assess the safety, pharmacokinetics,
      pharmacodynamics and exploratory efficacy of oral CS-0777 (0.1, 0.3 and 0.6 mg),
      administered once weekly or every other week for 12 weeks. CS-0777 resulted in a
      pronounced, dose-dependent decrease in lymphocytes and CD4 T cell subsets, which
      returned to baseline within 4 weeks after the last dose. Overall, CS-0777 was
      safe and well-tolerated. These results require confirmation in a double-blind,
      placebo-controlled and adequately powered phase 2 study in MS.

PMID- 22465064
TI  - Molecular organization of bacterial membrane lipids in mixed systems--A
      comprehensive monolayer study combined with Grazing Incidence X-ray Diffraction
      and Brewster Angle Microscopy experiments.
AB  - To properly design and investigate new antibacterial drugs a detailed description
      of the organization of bacterial membrane is highly important. Therefore in this
      work we performed a comprehensive characteristic of the Langmuir monolayers
      composed of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) mixed in
      a wide range of composition and treated as an artificial cytoplasmic layer of
      bacterial membrane. To obtain detailed information on the properties of these
      films we combined the analysis of the surface pressure-area curves with the
      surface potential measurements, Brewster Angle Microscopy studies and Grazing
      Incidence X-ray Diffraction experiments. It was found that the investigated
      phospholipids mix nonideally in the monolayers and that the most favorable
      packing of molecules occurs at their equimolar proportion. This is directly
      connected with the formation of hydrogen bonds between both types of molecules in
      the system. All the collected experimental data evidenced that
      dipalmitoylphosphatidylethanolamine (DPPE) and dipalmitoylphosphatidylglycerol
      (DPPG) form highly ordered associates of fixed (DPPE:DPPG 1:1) stoichiometry. The
      obtained results allow one to conclude a nonuniform distribution of lipids in
      bacterial membranes and the existence of domains composed of the investigated
      phospholipids. The latter seems to be of great importance in the perspective of
      further studies on the mechanism of action of antibacterial agents.

PMID- 22465065
TI  - A comparison of the behavior of cholesterol, 7-dehydrocholesterol and ergosterol
      in phospholipid membranes.
AB  - A molecular description of the effect of incorporation of cholesterol (CHOL), 7
      dehydrocholesterol (7DHC) and ergosterol (ERGO) on the structure of DPPC or EggPC
      liposomes is provided. Data obtained from ATR-IR spectroscopy, detergent
      solubility and zeta potential measurements show that the insertion of the various
      sterols alters the packing arrangement of the tails and headgroup of the PC
      lipids and may lead to lipid domain formation. On a molecular basis, the
      differences in lipid packing architecture are traced to differences between the
      ring and tail structure of the three sterols and these differences in structure
      produce different effects in DPPC liposomes in the gel phase and EggPC liposomes
      in the fluid phase. Specifically, CHOL has a relatively flat and linear structure
      and among the three sterols, shows the strongest molecular interactions with DPPC
      and EggPC lipids. An extra double bond in the fused ring of 7DHC hinders a
      tightly packing arrangement with DPPC lipids and leads to less domain formation
      than CHOL whereas 7DHC clearly produces more lipid domain formation in EggPC.
      ERGO produces similar structural changes to 7DHC in the tail and headgroup region
      of DPPC. Nevertheless, ERGO incorporation into DPPC liposomes produces more
      domain formation than 7DHC.

PMID- 22465066
TI  - Topology and lipid selectivity of pulmonary surfactant protein SP-B in membranes:
      Answers from fluorescence.
AB  - Contradictory results have been reported with respect to the depth of penetration
      and the orientation of pulmonary surfactant protein SP-B in phospholipid
      membranes and its relative selectivity to interact with anionic over zwitterionic
      phospholipid species. In the present study we have re-evaluated lipid-protein
      interactions of SP-B by analysing Forster resonance energy transfer (FRET)
      efficiencies, obtained from time-resolved measurements, from the single
      tryptophan in SP-B to different fluorescently labelled phospholipids in matrix
      bilayers made of either pure phosphatidylcholine (POPC) or the full lipid extract
      obtained from purified surfactant. In the background of POPC membranes SP-B
      exhibits a certain level of selectivity for anionic fluorescent phospholipids
      over the corresponding zwitterionic analogues, but apparently no preference for
      phosphatidylglycerol over other anionic species such as phosphatidylserine. No
      selectivity was detected in membranes made of full surfactant lipids, indicating
      that specific lipid-protein binding sites could already be occupied by endogenous
      anionic phospholipids. Furthermore, we have analysed the fit of two different
      models of how SP-B could be orientated with respect to phospholipid membrane
      surfaces to the FRET data. The FRET results are consistent with topology models
      in which the protein has a superficial orientation, with no regions of exclusion
      by the protein to the access of phospholipids, both in POPC membranes and in
      membranes made of the whole surfactant lipid fraction. This discards a deep
      penetration of the protein into the core of bilayers and suggests that most
      hydrophobic segments of SP-B could participate in protein-protein instead of
      lipid-protein interactions.

PMID- 22465067
TI  - Physicochemical characterization of anionic lipid-based ternary siRNA complexes.
AB  - Physicochemical characterization is a useful tool in understanding lipoplex
      assemblies and their correlation to biological activity. Anionic lipid-based
      ternary siRNA complexes composed of anionic liposomes (DOPG/DOPE), calcium ions
      and siRNA, have recently been shown to be safe and efficient in a breast cancer
      cell culture model. In the present work, the effects of various formulation
      parameters such as liposome composition (DOPG/DOPE ratio) and anionic
      lipid/Ca2+/siRNA molar charge ratio, on the physicochemical attributes (particle
      size, surface charge, siRNA loading efficiency and serum stability) of these
      ternary anionic lipoplexes were evaluated. Particle size, siRNA loading
      efficiency and serum stability correlated with the in vitro silencing efficiency
      of these lipoplexes. For example, large lipoplex particles (5/2.5/1 anionic
      lipid/Ca2+/siRNA molar charge ratio) showed less efficient silencing while
      absolute serum stability and high siRNA loading (1.3/2.5/1 anionic
      lipid/Ca2+/siRNA molar charge ratio), exhibited maximum silencing in breast
      cancer cells. The physicochemical properties also indicated that the siRNA exists
      in the complexed and/or encapsulated form within the lipoplexes, depending on the
      anionic lipid/siRNA charge ratio. Based on these studies a model representing
      lipid-siRNA association within the anionic lipoplexes prepared under various
      formulation conditions is proposed. Physicochemical attributes can be utilized to
      estimate in vitro activity of lipid-siRNA complexes and understand their
      morphology.

PMID- 22465068
TI  - Flexibility of the PDZ-binding motif in the micelle-bound form of Jagged-1
      cytoplasmic tail.
AB  - Human Jagged-1, one of the ligands of Notch receptors, is a transmembrane protein
      composed of a large extracellular region and a 125-residue cytoplasmic tail which
      bears a C-terminal PDZ recognition motif. To investigate the interaction between
      Jagged-1 cytoplasmic tail and the inner leaflet of the plasma membrane we
      determined, by solution NMR, the secondary structure and dynamics of the
      recombinant protein corresponding to the intracellular region of Jagged-1,
      J1_tmic, bound to negatively charged lysophospholipid micelles. NMR showed that
      the PDZ binding motif is preceded by four alpha-helical segments and that,
      despite the extensive interaction between J1_tmic and the micelle, the PDZ
      binding motif remains highly flexible. Binding of J1_tmic to negatively charged,
      but not to zwitterionic vesicles, was confirmed by surface plasmon resonance. To
      study the PDZ binding region in more detail, we prepared a peptide corresponding
      to the last 24 residues of Jagged-1, J1C24, and different phosphorylated variants
      of it. J1C24 displays a marked helical propensity and undergoes a coil-helix
      transition in the presence of negatively charged, but not zwitterionic,
      lysophospholipid micelles. Phosphorylation at different positions drastically
      decreases the helical propensity of the peptides and abolishes the coil-helix
      transition triggered by lysophospholipid micelles. We propose that
      phosphorylation of residues upstream of the PDZ binding motif may shift the
      equilibrium from an ordered, membrane-bound, interfacial form of Jagged-1 C
      terminal region to a more disordered form with an increased accessibility of the
      PDZ recognition motif, thus playing an indirect role in the interaction between
      Jagged-1 and the PDZ-containing target protein.

PMID- 22465070
TI  - Baroreflex sensitivity during rest and executive functioning in attention
      deficit/hyperactivity disorder. The TRAILS study.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) often show
      executive function (EF) problems and neurophysiological hypoarousal. Baroreceptor
      activation, as part of the baroreflex short-term blood pressure regulatory
      mechanism, has been linked to cortical inhibition and attenuated cognitive
      attentional functioning. We investigated the hypothesis that higher resting
      baroreflex sensitivity (BRS) predicts poorer EF performance in children with
      ADHD. EF measures of speed and accuracy were regressed upon resting BRS in 10-12
      year-old children with ADHD from a clinic-referred sample (n=181) and healthy
      (n=194) and clinic-referred (n=260) comparison samples. Resting BRS was
      positively associated with poorer EF performance (e.g., response variability,
      working memory, response inhibition), especially in ADHD combined type, boys, and
      unmedicated children. Comparison samples partly suggested negative associations.
      We conclude that higher resting BRS is related to poorer cognitive performance in
      children with ADHD. Findings suggest afferent influences of the body's visceral
      state on higher-order cognitive functioning and imply energetic state
      dysregulation in ADHD.

PMID- 22465069
TI  - Autonomous transmembrane segment S4 of the voltage sensor domain partitions into
      the lipid membrane.
AB  - The S4 transmembrane segment in voltage-gated ion channels, a highly basic alpha
      helix, responds to changes in membrane potential and induces channel opening.
      Earlier work by others indicates that the S4 segment interacts with lipids in
      plasma membrane, but its mechanism is unclear. Working with synthetic tryptophan
      labeled S4 peptides, we characterized binding of autonomous S4 to lipid
      membranes. The binding free energy (5.2 +/- 0.2 kcal/mol) of the peptide-lipid
      interaction was estimated from the apparent dissociation constants, determined
      from the changes in anisotropy of tryptophan fluorescence induced by addition of
      lipid vesicles with 30 mol% phosphatidylglycerol. The results are in good
      agreement with the prediction based on the Wimley-White hydrophobicity scale for
      interfacial (IF) binding of an alpha-helical peptide to the lipid bilayer (6.98
      kcal/mol). High salt inhibited the interaction, thus indicating that the
      peptide/membrane interaction has both electrostatic and non-electrostatic
      components. Furthermore, the synthetic S4 corresponding to the Shaker potassium
      channel was found to spontaneously penetrate into the negatively charged lipid
      membrane to a depth of about 9 A. Our results revealed important biophysical
      parameters that influence the interaction of S4 with the membrane: they include
      fluidity, surface charge, and surface pressure of the membrane, and the at
      helicity and regular spacing of basic amino-acid residues in the S4 sequence.

PMID- 22465071
TI  - Transcription of genes involved in fat metabolism in chicken embryos exposed to
      the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist GW7647
      or to perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA).
AB  - Perfluoroalkyl acids (PFAAs) such as perfluorooctane sulfonate (PFOS) and
      perfluorooctanoic acid (PFOA) are developmental toxicants in various animal
      classes, including birds. Both compounds interact with peroxisome proliferator
      activated receptors (PPARs), but it is not known whether activation of PPARs is
      involved in their embryo toxicity in birds. We exposed chicken embryos via egg
      injection at a late developmental stage to GW7647, a potent PPARalpha agonist in
      mammals, and to PFOS or PFOA. Mortality was induced by PFOS and PFOA but not by
      GW7647. Transcripts of a number of genes activated by PPARalpha agonists in
      mammals were analyzed in liver and kidney of 18-day-old embryos. Several of the
      genes were induced in both liver and kidney following exposure to GW7647.
      Treatment with PFOA resulted in induction of acyl-coenzyme A oxidase mRNA in
      liver, whereas none of the genes were significantly induced by PFOS treatment. No
      up-regulation of gene transcription was found in kidney following treatment with
      PFOS or PFOA. Principal component analysis showed that PFOA caused an mRNA
      expression pattern in liver more similar to the pattern induced by GW7647 than
      PFOS did. Our findings do not support that the embryo mortality by PFOS and PFOA
      in chicken embryos involves PPARalpha activation.

PMID- 22465072
TI  - Asymmetric liposome particles with highly efficient encapsulation of siRNA and
      without nonspecific cell penetration suitable for target-specific delivery.
AB  - The discovery of siRNA has been an important step in gene therapy, but the
      problem of delivering siRNA to a target organ limits its use as a therapeutic
      drug. Liposomes can be used as a nonviral vector to deliver siRNA to target
      cells. In this study we developed a novel method of producing asymmetric liposome
      particles (ALPs) with highly efficient siRNA encapsulation. Two kinds of lipid
      inverted micelles were prepared for the purpose of obtaining ALPs. The inner one
      is composed of ionizable cationic 1,2-dioleoyl-3-dimethylammonium-propane (DODAP)
      and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), which entrap siRNA, and
      the outer one is composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),
      DOPE, polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine
      (PEG-PE), and cholesterol. After mixing the inverted micelles, ALPs encapsulating
      siRNA were obtained by solvent evaporation and dialysis. This process allowed
      more than 90% siRNA encapsulation as well as the negatively charged surface. The
      ALPs protected siRNA from ribonuclease A degradation. ALPs without any surface
      modification elicited almost no uptake into cells, while the surface-modified
      ALPs with a polyarginine peptide (R12) induced nonspecific cell penetration. The
      conjugation of the anti-human epidermal growth factor receptor antibody (anti
      EGFR) to ALPs induces an EGFR-mediated uptake into the non-small cell lung cancer
      cell lines but not into NIH-3T3 cells without the receptor. The siRNA
      encapsulated in ALPs showed the R12- or anti-EGFR-dependent target gene silencing
      in NCI-H322 cells. These properties of ALPs are useful for target-specific
      delivery of siRNA after modification of ALPs with a target-specific ligand.

PMID- 22465073
TI  - Saturated fatty acid and TLR signaling link beta cell dysfunction and islet
      inflammation.
AB  - Consumption of foods high in saturated fatty acids (FAs) as well as elevated
      levels of circulating free FAs are known to be associated with T2D. Though
      previous studies showed inflammation is crucially involved in the development of
      insulin resistance, how inflammation contributes to beta cell dysfunction has
      remained unclear. We report here the saturated FA palmitate induces beta cell
      dysfunction in vivo by activating inflammatory processes within islets. Through a
      combination of in vivo and in vitro studies, we show beta cells respond to
      palmitate via the TLR4/MyD88 pathway and produce chemokines that recruit
      CD11b(+)Ly-6C(+) M1-type proinflammatory monocytes/macrophages to the islets.
      Depletion of M1-type cells protected mice from palmitate-induced beta cell
      dysfunction. Islet inflammation also plays an essential role in beta cell
      dysfunction in T2D mouse models. Collectively, these results demonstrate a clear
      mechanistic link between beta cell dysfunction and inflammation mediated at least
      in part via the FFA-TLR4/MyD88 pathway.

PMID- 22465075
TI  - Structural analysis of fMRI data: a surface-based framework for multi-subject
      studies.
AB  - We present a method for fMRI data group analysis that makes the link between two
      distinct frameworks: surface-based techniques, which process data in the domain
      defined by the surface of the cortex, and structural techniques, which use object
      based representations of the data as opposed to voxel-based ones. This work is a
      natural surface-based extension of the volume-based structural approach presented
      in a previous paper. A multi-scale surface-based representation of individual
      activation maps is first computed for each subject. Then the inter-subject
      matching and the activation detection decision are performed jointly by
      optimization of a Markovian model. Finally, a significance measure is computed in
      a non-parametric way for the results, in order to assess their relevance and
      control the risk of type I error. The method is applied on simulated and real
      data and the results are compared to those produced by standard analyses. The
      surface-based structural analysis is shown to be particularly robust to inter
      subject spatial variability and to produce relevant results with good specificity
      and sensitivity. We also demonstrate the advantages of the surface-based approach
      by comparing with the results of a 3D structural analysis.

PMID- 22465076
TI  - Generalized pixel profiling and comparative segmentation with application to
      arteriovenous malformation segmentation.
AB  - Extraction of structural and geometric information from 3-D images of blood
      vessels is a well known and widely addressed segmentation problem. The
      segmentation of cerebral blood vessels is of great importance in diagnostic and
      clinical applications, with a special application in diagnostics and surgery on
      arteriovenous malformations (AVM). However, the techniques addressing the problem
      of the AVM inner structure segmentation are rare. In this work we present a novel
      method of pixel profiling with the application to segmentation of the 3-D
      angiography AVM images. Our algorithm stands out in situations with low
      resolution images and high variability of pixel intensity. Another advantage of
      our method is that the parameters are set automatically, which yields little
      manual user intervention. The results on phantoms and real data demonstrate its
      effectiveness and potentials for fine delineation of AVM structure.

PMID- 22465074
TI  - The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis.
AB  - Chronic inflammation is a hallmark of atherosclerosis, but its transcriptional
      underpinnings are poorly understood. We show that the transcriptional repressor
      Bcl6 is an anti-inflammatory regulator whose loss in bone marrow of Ldlr(-/-)
      mice results in severe atherosclerosis and xanthomatous tendonitis, a virtually
      pathognomonic complication in patients with familial hypercholesterolemia.
      Disruption of the interaction between Bcl6 and SMRT or NCoR with a peptide
      inhibitor in vitro recapitulated atherogenic gene changes in mice transplanted
      with Bcl6-deficient bone marrow, pointing to these cofactors as key mediators of
      Bcl6 inflammatory suppression. Using ChIP-seq, we reveal the SMRT and NCoR
      corepressor cistromes, each consisting of over 30,000 binding sites with a nearly
      50% overlap. While the complete cistromes identify a diversity of signaling
      pathways, the Bcl6-bound subcistromes for each corepressor are highly enriched
      for NF-kappaB-driven inflammatory and tissue remodeling genes. These results
      reveal that Bcl6-SMRT/NCoR complexes constrain immune responses and contribute to
      the prevention of atherosclerosis.

PMID- 22465078
TI  - Automatic motion compensation of free breathing acquired myocardial perfusion
      data by using independent component analysis.
AB  - Images acquired during free breathing using first-pass gadolinium-enhanced
      myocardial perfusion magnetic resonance imaging (MRI) exhibit a quasiperiodic
      motion pattern that needs to be compensated for if a further automatic analysis
      of the perfusion is to be executed. In this work, we present a method to
      compensate this movement by combining independent component analysis (ICA) and
      image registration: First, we use ICA and a time-frequency analysis to identify
      the motion and separate it from the intensity change induced by the contrast
      agent. Then, synthetic reference images are created by recombining all the
      independent components but the one related to the motion. Therefore, the
      resulting image series does not exhibit motion and its images have intensities
      similar to those of their original counterparts. Motion compensation is then
      achieved by using a multi-pass image registration procedure. We tested our method
      on 39 image series acquired from 13 patients, covering the basal, mid and apical
      areas of the left heart ventricle and consisting of 58 perfusion images each. We
      validated our method by comparing manually tracked intensity profiles of the
      myocardial sections to automatically generated ones before and after registration
      of 13 patient data sets (39 distinct slices). We compared linear, non-linear, and
      combined ICA based registration approaches and previously published motion
      compensation schemes. Considering run-time and accuracy, a two-step ICA based
      motion compensation scheme that first optimizes a translation and then for non
      linear transformation performed best and achieves registration of the whole
      series in 32+/-12s on a recent workstation. The proposed scheme improves the
      Pearsons correlation coefficient between manually and automatically obtained time
      intensity curves from .84+/-.19 before registration to .96+/-.06 after
      registration.

PMID- 22465077
TI  - Machine learning and radiology.
AB  - In this paper, we give a short introduction to machine learning and survey its
      applications in radiology. We focused on six categories of applications in
      radiology: medical image segmentation, registration, computer aided detection and
      diagnosis, brain function or activity analysis and neurological disease diagnosis
      from fMR images, content-based image retrieval systems for CT or MRI images, and
      text analysis of radiology reports using natural language processing (NLP) and
      natural language understanding (NLU). This survey shows that machine learning
      plays a key role in many radiology applications. Machine learning identifies
      complex patterns automatically and helps radiologists make intelligent decisions
      on radiology data such as conventional radiographs, CT, MRI, and PET images and
      radiology reports. In many applications, the performance of machine learning
      based automatic detection and diagnosis systems has shown to be comparable to
      that of a well-trained and experienced radiologist. Technology development in
      machine learning and radiology will benefit from each other in the long run. Key
      contributions and common characteristics of machine learning techniques in
      radiology are discussed. We also discuss the problem of translating machine
      learning applications to the radiology clinical setting, including advantages and
      potential barriers.

PMID- 22465079
TI  - Imaging the femoral cortex: thickness, density and mass from clinical CT.
AB  - There is growing evidence that focal thinning of cortical bone in the proximal
      femur may predispose a hip to fracture. Detecting such defects in clinical CT is
      challenging, since cortices may be significantly thinner than the imaging
      system's point spread function. We recently proposed a model-fitting technique to
      measure sub-millimetre cortices, an ill-posed problem which was regularized by
      assuming a specific, fixed value for the cortical density. In this paper, we
      develop the work further by proposing and evaluating a more rigorous method for
      estimating the constant cortical density, and extend the paradigm to encompass
      the mapping of cortical mass (mineral mg/cm(2)) in addition to thickness.
      Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs,
      with high resolution measurements from a micro-CT scanner providing the gold
      standard. The results demonstrate robust, accurate measurement of peak cortical
      density and cortical mass. Cortical thickness errors are confined to regions of
      thin cortex and are bounded by the extent to which the local density deviates
      from the peak, averaging 20% for 0.5mm cortex.

PMID- 22465080
TI  - The dynamics of cortico-thalamo-cortical interactions at the transition from pre
      ictal to ictal LFPs in absence epilepsy.
AB  - PURPOSE: Generalized spike and wave discharges (SWD) are generated within the
      cortico-thalamo-cortical system. However the exact interactions between cortex
      and different thalamic nuclei needed for the generation and maintenance of SWD
      are still to be elucidated. This study aims to shed more light on these
      interactions via multisite cortical and thalamic local-field-potential
      recordings. METHODS: WAG/Rij rats were equipped with multiple electrodes
      targeting layers 4 to 6 of the somatosensory-cortex, rostral and caudal RTN, VPM,
      anterior (ATN)- and posterior (Po) thalamic nucleus. The maximal-association
      strength between signals was calculated for pre-ictal->ictal transition periods
      and in control periods using non-linear-association-analysis. Dynamics of changes
      in coupling-direction and time-delays between channels were analyzed. RESULTS:
      Earliest and strongest increases in coupling-strength were seen between cortical
      layers 5/6 and Po. Other thalamic nuclei became later involved in SWD activity.
      During the first 500ms of SWDs the cortex guided most thalamic nuclei while
      cortex and Po kept a bidirectional crosstalk. Most thalamic nuclei started to
      guide the Po until the end of the SWD. While the rostral RTN showed increased
      coupling with Po, the caudal RTN decoupled. Instead, it directed its activity to
      the rostral RTN. CONCLUSIONS: Next to the focal cortical instigator zone of SWDs,
      the Po seems crucial for their occurrence. This nucleus shows early increases in
      coupling and is the only nucleus which keeps a bidirectional crosstalk to the
      cortex within the first 500ms of SWDs. Other thalamic nuclei seem to have only a
      function in SWD maintenance. Rostral and caudal-RTN have opposite roles in SWD
      occurrence.

PMID- 22465081
TI  - Amino acid disorders detected by quantitative amino acid HPLC analysis in
      Thailand: an eight-year experience.
AB  - BACKGROUND: Amino acid disorders are a major group of inborn errors of metabolism
      (IEM) with variable clinical presentations. This study was aimed to provide the
      data of amino acid disorders detected in high-risk Thai patients referred to our
      metabolic lab from all over the country. METHODS: From 2001 to 2009, we analyzed
      amino acids by HPLC in 1214 plasma and cerebrospinal fluid specimens. These
      specimens were obtained from patients with clinical suspicion of IEM or with
      positive newborn screening. The clinical data of the patients with confirmed
      diagnoses of amino acid disorders were also analyzed. RESULTS: Fifty-eight
      patients were diagnosed with amino acid disorders, including 20 cases (34.5%)
      with maple syrup urine disease, 13 (22.4%) with phenylketonuria and
      hyperphenylalaninemia, 13 (22.4%) with nonketotic hyperglycinemia, 9 (15.5%) with
      urea cycle defects, 2 (3.4%) with classical homocystinuria, and 1 (1.7%) with
      ornithine aminotransferase deficiency. There was considerable delay in diagnoses
      which led to poor outcomes in most patients. CONCLUSION: The prevalence of amino
      acid disorders in Thailand is distinct from other countries. This will guide the
      selection of the prevalent IEM for the future expansion of newborn screening
      program in this country.

PMID- 22465082
TI  - Long-term follow-up of four patients affected by HHH syndrome.
AB  - BACKGROUND: In hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome,
      impaired ornithine transport across the mitochondrial membrane causes ornithine
      accumulation in cytoplasm. The resulting mitochondrial ornithine deficiency leads
      to reduced clearance of ammonia through the urea cycle. First described in 1969,
      no long-term follow-up has been reported. METHODS: Four patients were followed up
      for 11 to 38y. Diagnosis was made by plasma amino acid analysis using ion
      exchange chromatography, HPLC orotic acid measurement, and (14)C-ornithine
      incorporation study using cultured fibroblasts. DNA from fibroblasts was
      amplified and sequenced. Blood ammonia was controlled by restriction of protein
      intake. RESULTS: All patients had reduced (14)C-ornithine incorporation. Mutation
      analysis revealed two novel mutations in the ORNT1 gene. Neurologic outcome
      included memory loss, low IQ, tremor, spasticity of extremities, bladder
      incontinence, and abnormal gait. Neuroimaging revealed subcortical, cerebral and
      cerebellar atrophy, sparing the basal ganglia. Individual examination showed
      pyramidal signs, cerebellar signs, paraplegia, movement disorder, dystonia, and
      epilepsy. One patient had 3 pregnancies, one of which resulted in intrauterine
      growth retardation. CONCLUSIONS: Our patients expand the clinical phenotype of
      adults with HHH. Long-term follow-up showed serious neurologic outcomes in all
      patients; three patients clearly exhibited progression of neurologic dysfunction
      despite control of hyperammonemia. Intracellular ornithine deficiency may
      adversely affect brain functions.

PMID- 22465083
TI  - Discrimination of clinical stages in non-small cell lung cancer patients by serum
      HSP27 and HSP70: a multi-institutional case-control study.
AB  - INTRODUCTION: Lung cancer represents a major healthcare problem. Accordingly,
      there is an urgent need to identify serum biomarkers for early diagnosis of lung
      pathology. We have recently described that patients with manifest COPD evidence
      elevated levels of heat shock proteins (HSPs). Based on these data, we speculated
      whether HSPs are also increased in patients with diagnosed lung cancer. METHODS:
      Serum levels of HSP27, phospho-HSP27 (pHSP27) and HSP70 in patients with non
      small cell lung cancer (NSCLC) diagnosed at an early (stages I-II, n=37) or
      advanced (stages IIIA-IV, n=72) stage were determined by using ELISA. Healthy
      smokers (n=24), healthy never-smoker volunteers (n=33) and COPD patients (n=34)
      according to GOLD classification served as control population. RESULTS: Serum
      levels of HSP27 were elevated in patients with NSCLC diagnosed at an early or
      advanced stage when compared with both healthy control groups (P<0.005 and
      P<0.0001 respectively). Statistically significant differences were furthermore
      found between the groups of patients with early vs. advanced stage NSCLC
      (P=0.0021). Serum levels of HSP70 were also significantly elevated in patients
      with NSCLC diagnosed at an early or at an advanced stage when compared with
      either healthy control groups (P=0.0028 and P<0.0001 respectively). In univariate
      logistic regression models including healthy subjects and patients with NSCLC,
      HSP70 had an area under the curve (AUC) of 0.779 (P<0.0001) and HSP27 showed an
      AUC of 0.870 (P<0.0001). CONCLUSION: Our data suggest that serum HSP27 levels
      might serve as a possible tool to discriminate between early and advanced stages
      NSCLC.

PMID- 22465084
TI  - Pulsed fluoroscopy in ureteroscopy and percutaneous nephrolithotomy.
AB  - OBJECTIVE: To assess the impact of pulsed fluoroscopy (PF) at a rate of 4 frames
      per seconds (fps) on the total fluoroscopy time during ureteroscopy (URS) and
      percutaneous nephrolithotomy (PCNL). METHODS: A retrospective review of
      prospectively collected data was performed for consecutive patients undergoing
      URS and PCNL by a single surgeon between July 2009 and July 2011. PF was
      routinely used in all URS procedures since January 2011 and in all PCNL
      procedures since November 2010. Before these dates, standard fluoroscopy (SF) at
      a rate of 30 fps was used. Patient and stone characteristics together with
      operative data were compared using univariate and multivariate analyses. RESULTS:
      There were a total of 163 URS (117 SF and 46 PF) and 100 PCNL (50 SF and 50 PF).
      In the URS cohort, there were no significant differences between both SF and PF
      groups in terms of age, gender, body mass index, stone location, and multiplicity
      (P >=.20). For both URS and PCNL cohorts, the duration of surgery and stone-free
      rates were comparable in both SF and PF groups (P >=.06). Compared with SF
      groups, patients in the PF groups were exposed to significantly less fluoroscopy
      during URS (109.1 vs. 44.1 sec, P<0.001) and PCNL (341.1 vs. 121.5 sec, P<0.001).
      These differences in mean fluoroscopy times retained their significance in
      multivariate analyses (P<.001). CONCLUSION: The use of PF during URS and PCNL was
      associated with significantly lower fluoroscopy time, thus reducing radiation
      exposure to both patients and personnel.

PMID- 22465085
TI  - Factors affecting stone-free rate and complications of percutaneous
      nephrolithotomy for treatment of staghorn stone.
AB  - OBJECTIVE: To determine factors affecting the stone-free rate and complications
      of percutaneous nephrolithotomy (PNL) for treatment of staghorn stones. METHODS:
      The computerized database of patients who underwent PNL for treatment of staghorn
      stones between January 2003 and January 2011 was reviewed. All perioperative
      complications were recorded and classified according to modified Clavien
      classification system. The stone-free rate was evaluated with low-dose
      noncontrast computed tomography (CT). Univariate and multivariate statistical
      analyses were performed to determine factors affecting stone-free and
      complication rates. RESULTS: The study included 241 patients (125 male and 116
      female) with a mean age of 48.7 +/-14.3 years. All patients underwent 251 PNL (10
      patients had bilateral stones). The stone-free rate of PNL monotherapy was 56%
      (142 procedures). At 3 months, the stone-free rate increased to 73% (183 kidneys)
      after shock wave lithotripsy. Independent risk factors for residual stones were
      complete staghorn stone and presence of secondary calyceal stones (relative risks
      were 2.2 and 3.1, respectively). The complication rate was 27% (68 PNL).
      Independent risk factors for development of complications were performance of the
      procedure by urologists other than experienced endourologist and positive
      preoperative urine culture (relative risks were 2.2 and 2.1, respectively).
      CONCLUSION: Factors affecting the incidence of residual stones after PNL are
      complete staghorn stones and the presence of secondary calyceal stones.
      Complications are significantly high if PNL is not performed by an experienced
      endourologist or if preoperative urine culture is positive.

PMID- 22465086
TI  - Initial use of LESS for the ACE Malone procedure in children.
AB  - The Malone antegrade continence enema is effective in improving fecal continence
      in neurogenic bowel. We were able to perform this procedure laparoscopically via
      a single incision in a patient with spina bifida and fecal incontinence who did
      not require bladder reconstruction.

PMID- 22465087
TI  - Pediatric urolithiasis in Taiwan: a nationwide study, 1997-2006.
AB  - OBJECTIVE: To investigate the prevalence, incidence, associated risk factors, and
      treatment of pediatric urolithiasis in Taiwan. METHODS: The present study used a
      subset of the National Health Insurance Research Database, known as the
      Longitudinal Health Insurance Database 2005, which contains the data for all paid
      medical benefit claims from 1997 to 2006 for a subset of 1 million beneficiaries
      randomly drawn from the population of 22.72 million individuals during any part
      of the calendar year 2005. Our analysis included the data of all newly diagnosed
      pediatric patients with an "International Classification of Disease, 9th
      revision," diagnosis of urolithiasis from 1997 through 2006. RESULTS: A total of
      1679 pediatric subjects who had newly diagnosed urolithiasis without a previous
      attack were identified from 1997 to 2006 as the study sample. Of the 1679
      patients, 808 were boys (48.1%) and 871 were girls (51.9%). The incidence rate of
      urolithiasis in 2005 was 0.047%. The peak age of pediatric stone occurrence in
      the study sample was 15-18 years (49.6%). The most common associated disease was
      urinary tract infection (34.1% of all subjects). The occurrence rate of pediatric
      urolithiasis correlated significantly with the urbanization level of the
      residence and geographic area. CONCLUSION: Using a nationwide, population-based
      study provides important clinical and epidemiologic information regarding
      pediatric urolithiasis. Additional studies are warranted to determine the effect
      of geographic area and urbanization level on the occurrence of pediatric stone
      disease.

PMID- 22465088
TI  - Psychological risk may influence drop-out prior to bariatric surgery.
AB  - BACKGROUND: Factors necessitating a delay before psychological clearance for
      bariatric surgery have been previously identified; however, research has not
      examined why patients who begin the preoperative evaluation fail to complete
      surgery or drop-out of bariatric programs. This study sought to explore the
      potential psychosocial reasons for a failure to reach bariatric surgery. The
      setting was an academic medical center. METHODS: Data were analyzed from 129
      patients psychologically evaluated for bariatric surgery who had failed to reach
      surgery after 15 months. Medical records were reviewed for demographics, body
      mass index, and psychiatric variables. RESULTS: The most common reasons for not
      reaching surgery included withdrawal from the program, outstanding program
      requirements, self-canceled surgery, moving out of the area, insurance denial,
      switching to non-surgical weight management, or death. Patients with outstanding
      program requirements were psychosocially different from patients who had not
      achieved surgery for other reasons. They were significantly more likely to be
      involved in outpatient behavioral health treatment (chi-square = 12.90, P < .05),
      to be taking psychotropic medications (chi-square = 15.17, P < .05), and to have
      met the criteria for current or past alcohol abuse/dependence (chi-square =
      23.70, P < .01), and there was a trend for previous inpatient hospitalizations
      (chi-square = 11.59, P < .07). CONCLUSION: Patients who failed to complete
      outstanding program requirements often had significant psychiatric and/or
      substance abuse/dependence issues that required additional treatment. It is
      possible that these patients drop-out of the program due to unwillingness to
      complete psychiatric treatment recommendations. Continued screening of high-risk
      patients and the education of patients on the importance of managing these risks
      is indicated. However, patients may choose to leave programs once education has
      been provided or treatment mandated.

PMID- 22465089
TI  - Over-nutrition and metabolic cardiomyopathy.
AB  - Cardiovascular disease, which accounts for the highest morbidity and mortality in
      the United States, has several major risk factors, including aging and diabetes.
      Overweight and obesity, especially abdominal obesity, have been increasingly
      implicated as independent risk factors in the development of cardiovascular
      disease. Metabolic and/or diabetic cardiomyopathy has been especially associated
      with excess body weight caused by chronic over-nutrition and high-fat feeding. In
      the initial stages, obesity is now understood to cause significant dysregulation
      of cardiac fatty acid and glucose metabolism. These abnormalities are due, in
      part, to increased oxidative stress, which in turn can cause deleterious effects
      on intracellular signaling pathways that control cellular growth and
      proliferation. This increase in oxidative stress is coupled with reduced anti
      oxidant species and dysregulation of metabolic signaling pathways. The
      cardiomyopathy seen with obesity is associated with increased interstitial
      fibrosis and diastolic dysfunction. Over time, evolving abnormalities include
      hypertrophy and systolic dysfunction, eventually leading to heart failure.

PMID- 22465090
TI  - The ontogeny of acoustic individuality in the nasal calls of captive goitred
      gazelles, Gazella subgutturosa.
AB  - Individualistic voices are important for establishing personalized relationships
      among individuals. In young animals, individual vocal identity is affected by
      permanent changes of the acoustics due to the growth of their vocal apparatus.
      Different acoustic variables change uncoordinatedly, so vocal individuality
      should be repeatedly upgraded along development. We compared classifying accuracy
      of individuals and sexes by nasal calls in fast-growing goitred gazelles Gazella
      subgutturosa at two ontogenetic stages, juvenile (3-6 weeks of age) and
      adolescent (23-26 weeks of age). Juvenile "spring" nasal calls and adolescent
      "fall" nasal calls were examined in the same 35 calves (18 males, 17 females),
      wild-born in May and then hand-raised. Discriminate function analysis based on
      four formants, fundamental frequency, duration and three power quartiles,
      revealed an equally high potential of spring and fall calls to encode sex. The
      individuality was very high in both ages but significantly higher in fall calls.
      Classifying calls to individuals was based on the same three acoustic variables
      (fundamental frequency and third and fourth formants) in both ages, although
      their actual values changed uncoordinatedly from spring to fall in most subjects.
      Our results suggest updating acoustic individuality in nasal calls of adolescent
      goitred gazelles accordingly to the newly emerged acoustic variation.

PMID- 22465091
TI  - A novel series of l-2-benzyloxycarbonylamino-8-(2-pyridyl)-disulfidyloctanoic
      acid derivatives as histone deacetylase inhibitors: design, synthesis and
      molecular modeling study.
AB  - Histone deacetylases inhibitors (HDACIs) have become an attractive class of
      anticancer agents. In order to find some novel potent HDACIs, we designed and
      synthesized a series of l-2-benzyloxycarbonylamino-8-(2-pyridyl)
      disulfidyloctanoic acid derivatives. All compounds exhibited potent HDAC
      inhibitory activity, and two of them had similar potency to TSA. The introduction
      of 2-amino-4-phenylthiazole or 9-methyleneoxy-fluorenyl group at the surface
      recognize domain of these HDACIs could greatly increase their HDAC-inhibitory
      activity. Molecular modeling studies indicated that coordination of the zinc ion
      by these inhibitors, and formation of hydrogen bond and hydrophobic interaction
      between inhibitors and HDACs were essential for the HDAC-inhibitory activities of
      these inhibitors. Asp181, Asp269, Leu276 and Tyr308 in the active site of HDAC2
      gave favorable contributions for binding with all compounds.

PMID- 22465093
TI  - A new linear transfer theory and characterization method for image detectors.
      Part I: theory.
AB  - A new generalized linear transfer theory describing the signal and noise transfer
      in image detectors is presented, which can be applied to calculate the pixelwise
      first and second statistical moment of arbitrary experimental images including
      correlation between pixels. Similar to the existing notion of a point spread
      function describing the transfer of the first statistical moment (the average), a
      noise spread function is introduced to characterize the spatially resolved
      transfer and generation of noise (second central moment, covariance). It is also
      shown that previously used noise characteristics like the noise power spectrum
      and detection quantum efficiency, derived from plainly illuminated images,
      contain only partial information of the complete noise transfer.

PMID- 22465092
TI  - In vitro antimycoplasmal activity of Citrus bergamia essential oil and its major
      components.
AB  - Forty-two strains of Mycoplasma hominis (including PG21), 2 strain of Mycoplasma
      fermentans (Pg18 and K7), 1 strain of Mycoplasma pneumoniae (strain m129) were
      investigated for their susceptibilities to Citrus bergamia essential oil and to
      its major components (limonene, linalyl acetate and linalool). C. bergamia
      essential oil inhibited mycoplasmas at concentrations from 0.5 to 1% (MIC value
      as % v/v). M. hominis showed MIC(50) values of 0.5% and MIC(90) values of 1%; M.
      pneumoniae showed a MIC value of 0.5% while M. fermentans strains were inhibited
      by MIC values of 1%. M. pneumoniae and M. hominis shared the same susceptibility
      to linalyl acetate, with MIC values of 0.015% (corresponding to MIC(50) and
      MIC(90) for M. hominis); M. fermentans strains were less susceptible with MIC
      values of 0.12%. Among the major components tested, linalool showed higher
      activity against M. pneumoniae and M. fermentans (MIC values of 0.015 and 0.06%,
      respectively) but was less active against M. hominis (MIC(50) and MIC(90) values
      of both 1%); limonene was active against M. pneumoniae (MIC value of 0.03%) but
      was less active against M. fermentans (MIC values of 1%) and M. hominis (both
      MIC(50) and MIC(90) values of >=4%). The results indicated that C. bergamia
      essential oil and its major components had shown an interesting in vitro
      antimycoplasmal activity.

PMID- 22465095
TI  - Influence of bile on the absorption of halofantrine from lipid-based
      formulations.
AB  - The bioavailability of the poorly soluble model drug halofantrine, dosed in a soy
      bean oil solution or in a self-nanoemulsifying drug delivery system (SNEDDS), at
      two levels of lipid, was assessed in rats. Three rat models were used: intact
      rats, sham-operated rats and bile duct cannulated rats. The study showed no
      difference in the pharmacokinetic parameters between intact and sham-operated
      rats. T(max) increased with lipid load for both oil solution and SNEDDS, whereas
      C(max) and the absolute bioavailability were significantly higher for the SNEDDS
      at both lipid dosing levels. Bile duct cannulation of the rats reduced the C(max)
      and the absolute bioavailability of halofantrine significantly, by a factor of 2,
      for all 4 treatments. These data clearly demonstrate that bile has an importance
      for the absorption of drugs from lipid-based formulations independent of the
      type.

PMID- 22465094
TI  - Delineation of gilvocarcin, jadomycin, and landomycin pathways through
      combinatorial biosynthetic enzymology.
AB  - The exact sequence of events in biosyntheses of natural products is essential not
      only to understand and learn from nature's strategies and tricks to assemble
      complex natural products, but also for yield optimization of desired natural
      products, and for pathway engineering and muta-synthetic preparation of analogues
      of bioactive natural products. Biosyntheses of natural products were classically
      studied applying in vivo experiments, usually by combining incorporation
      experiments with stable-isotope labeled precursors with cross-feeding experiments
      of putative intermediates. Later genetic studies were dominant, which consist of
      gene cluster determination and analysis of gene inactivation experiments. From
      such studies various biosynthetic pathways were proposed, to a large extent just
      through in silico analyses of the biosynthetic gene clusters after DNA
      sequencing. Investigations of the complex biosyntheses of the angucycline group
      anticancer drugs landomycin, jadomycin and gilvocarcin revealed that in vivo and
      in silico studies were insufficient to delineate the true biosynthetic sequence
      of events. Neither was it possible to unambiguously assign enzyme activities,
      especially where multiple functional enzymes were involved. However, many of the
      intriguing ambiguities could be solved after in vitro reconstitution of major
      segments of these pathways, and subsequent systematic variations of the used
      enzyme mixtures. This method has been recently termed 'combinatorial biosynthetic
      enzymology'.

PMID- 22465096
TI  - Conformation of surface-decorating dextran chains affects the pharmacokinetics
      and biodistribution of doxorubicin-loaded nanoparticles.
AB  - Recent reports showed that subtle modifications of nanoparticle surface
      properties induced dramatic changes of interactions with serum proteins. The
      present work was aimed to investigate the effect of the conformation of dextran
      chains decorating the surface of poly(alkylcyanoacrylate) (PACA) nanoparticles on
      the pharmacokinetic and biodistribution of a model drug associated with the
      nanoparticles. Doxorubicin was associated with PACA nanoparticles prepared by
      anionic emulsion polymerization (AEP) (Dox-AEP) and redox radical emulsion
      polymerization (RREP) (Dox-RREP). Nanoparticles and the free drug (f-Dox) were
      injected intravenously to rats to determine the pharmacokinetic and
      biodistribution of doxorubicin. Curves of the pharmacokinetics showed a rapid
      phase of distribution followed by a slower elimination phase. Pharmacokinetic
      parameters of the distribution phase determined for the Dox-RREP were
      significantly different from those of f-Dox and Dox-AEP, while no difference was
      observed in the elimination phase of the three formulations. Rats treated with
      Dox-RREP showed lower Dox concentrations in liver but higher concentrations in
      heart, lungs, and kidneys compared to those treated with the other formulations.
      Dox-RREP exhibited a new type of stealth behavior characterized by a short
      circulation time and a rapid distribution in highly vascularized organs bypassing
      the MPS. The difference in pharmacokinetic and biodistribution observed between
      the drugs formulated with the two types of nanoparticles was attributed to the
      difference in the conformation of the dextran chains stranded on the nanoparticle
      surface.

PMID- 22465098
TI  - Role of renin-angiotensin-aldosterone system in adipose tissue dysfunction.
AB  - The renin-angiotensin-aldosterone system (RAAS) is known to be closely linked to
      the pathogenesis of insulin resistance. The angiotensin (Ang) II type 1 (AT1)
      receptor mediates the major effects of Ang II in adipose tissue, and blockade of
      the AT1 receptor improves insulin sensitivity, with enhanced adipocyte
      differentiation. In contrast, the role of angiotensin type 2 (AT2) receptor
      activation in insulin sensitivity is still controversial, although AT2 receptor
      functions are thought to be mutually antagonistic against those of the AT1
      receptor in the cardiovascular system. Aldosterone exerts its biological roles
      via the mineralocorticoid receptor (MR), and inhibition of MR signaling in
      adipose tissue ameliorates inflammation, with upregulation of insulin-mediated
      glucose transport and adipocyte differentiation. Clinical studies indicate that
      blockade of RAAS prevents the new onset of type 2 diabetes and improves the
      metabolic syndrome in diabetic patients. We here review the recent concepts of
      the roles of RAAS in adipose tissue.

PMID- 22465097
TI  - Identification of fibroblast growth factor-8b target genes associated with early
      and late cell cycle events in breast cancer cells.
AB  - Fibroblast growth factor-8 (FGF-8) is implicated in the development and
      progression of breast cancer and its levels are frequently elevated in breast
      tumors. The mechanisms driving FGF-8-mediated tumorigenesis are not well
      understood. Herein we aimed to identify target genes associated with FGF-8b
      mediated breast cancer cell proliferation by carrying out a cDNA microarray
      analysis of genes expressed in estrogen receptor negative S115 breast cancer
      cells treated with FGF-8b for various time periods in comparison with those
      expressed in non-treated cells. Gene and protein expression was validated for
      selected genes by qPCR and western blotting respectively. Furthermore, using
      TRANSBIG data, the expression of human orthologs of FGF-8-regulated genes was
      correlated to the Nottingham prognostic index and estrogen receptor status. The
      analysis revealed a number of significantly up- and down-regulated genes in
      response to FGF-8b at all treatment times. The most differentially expressed
      genes were genes related to cell cycle regulation, mitosis, cancer, and cell
      death. Several key regulators of early cell cycle progression such as Btg2 and
      cyclin D1, as well as regulators of mitosis, including cyclin B, Plk1, survivin,
      and aurora kinase A, were identified as novel targets for FGF-8b, some of which
      were additionally shown to correlate with prognosis and ER status in human breast
      cancer. The results suggest that in stimulation of proliferation FGF-8b not only
      promotes cell cycle progression through the G1 restriction point but also
      regulates key proteins involved in chromosomal segregation during mitosis and
      cytokinesis of breast cancer cells.

PMID- 22465099
TI  - Endocrine prevention and treatment of prostate cancer.
AB  - The major androgen within the prostate is dihydrotestosterone (DHT). DHT and
      5alpha-reductase are highly associated with prostate cancer. It has been
      hypothesised that inhibition of 5alpha-reductase activity might reduce the risk
      of prostate cancer development, slow tumour progression and even treat the
      existing disease. The basis for endocrine treatment of prostate cancer is to
      deprive the cancer cells of androgens. Every type of endocrine treatment carries
      adverse events which influence quality of life in different ways. 5alpha
      Reductase inhibitors (5-ARI) reduce risk of being diagnosed with prostate cancer
      but they do not eliminate it. By suppressing PSA from BPH and indolent prostate
      cancers 5-ARI enhances the ability of a rising PSA to define a group of men at
      increased risk of clinically significant prostate cancer. Also fewer high-grade
      cancers are missed because biopsy is more accurate in smaller prostates. Androgen
      deprivation is an effective treatment for patients with advanced prostate cancer.
      However, it is not curative, and creates a spectrum of unwanted effects that
      influence quality of life. Castration remains the frontline treatment for
      metastatic prostate cancer, where orchiectomy, oestrogen agonists, GnRH agonists
      and antagonists produce equivalent clinical responses. MAB is not significantly
      more effective than single agent GnRH agonist or orchiectomy. Nonsteroidal
      antiandrogen monotherapy is as effective as castration in treatment of locally
      advanced prostate cancer offering quality of life benefits. Neoadjuvant endocrine
      treatment has its place mainly in the external beam radiotherapy setting.
      Increasing data suggest IAD is as effective as continuous ADT. The decision
      regarding the type of androgen deprivation should be made individually after
      informing the patient of all available treatment options, including watchful
      waiting, and on the basis of potential benefits and adverse effects. There are
      new promising secondary or tertiary forms of endocrine therapies under
      evaluation, like CTP17A1 inhibitors and more potent antiandrogens including
      MDV3100, which give new hope for patients developing castration resistant
      prostate cancer.

PMID- 22465101
TI  - [Abdominal pain].

PMID- 22465102
TI  - Development of a novel method for simultaneous concentration of viruses and
      protozoa from a single water sample.
AB  - A novel method, electronegative membrane-vortex (EMV) method, was developed for
      simultaneous concentration of viruses and protozoa from a single water sample.
      Viruses and protozoa in a water sample were mixed with a cation solution and
      adsorbed on an electronegative membrane. Concentrated virus and protozoa samples
      were obtained as supernatant and pellet fractions, respectively, by vigorous
      vortex mixing of the membrane and centrifugation of the eluted material. The
      highest recovery efficiencies of model microbes from river water and tap water by
      this EMV method were obtained using a mixed cellulose ester membrane with a pore
      size of 0.45 MUm (Millipore) as the electronegative membrane and MgCl(2) as the
      cation solution. The recovery was 27.7-86.5% for poliovirus, 25.7-68.3% for
      coliphage Qbeta, 28.0-60.0% for Cryptosporidium oocysts, and 35.0-53.0% for
      Giardia cysts. The EMV method detected successfully indigenous viruses and
      protozoa in wastewater and river water samples from the Kofu basin, Japan,
      showing an overall positive rate of 100% (43/43) for human adenovirus, 79%
      (34/43) for norovirus GI, 65% (28/43) for norovirus GII, 23% (10/43) for
      Cryptosporidium oocysts, and 60% (26/43) for Giardia cysts. By direct DNA
      sequencing, a total of four genotypes (AI, AII, B, and G) of Giardia intestinalis
      were identified in the water samples, indicating that the river water was
      contaminated with feces from various mammals, including humans.

PMID- 22465103
TI  - Rapid detection of duck hepatitis virus type-1 by reverse transcription loop
      mediated isothermal amplification.
AB  - A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay
      for the detection of duck hepatitis virus type-1 (DHV-1) was established. Using
      primers specific to the highly conserved 3D gene of DHV-1, the developed RT-LAMP
      assay detected the viral RNA of DHV-1 extracted from both allantoic fluid and
      liver samples of infected ducks. The assay is as sensitive as RT-PCR, and shows
      no cross-reaction with other common avian viral and bacterial pathogens. In
      addition to detection via ethidium bromide staining following gel
      electrophoresis, naked-eye observation after staining with SYBR Green I dye can
      be used to detect RT-LAMP products; this enables field application of this assay.
      The findings demonstrate that RT-LAMP can serve as a helpful tool for the
      detection and surveillance of DHV-1 in the poultry industry.

PMID- 22465104
TI  - Establishment of rapid and specific real-time PCR assays for the detection of
      hepatitis B viral genotype in tibet.
AB  - Hepatitis B virus (HBV) with a C/D recombinant genotype is dominant in Tibet. A
      rapid, simple and specific genotyping system, consisting of three real-time PCR
      assays, was developed for the determination of genotypes C and D as well as two
      forms of recombinant C/D. Overall, 95% of the 22 samples were genotyped
      accurately. This system is considered to be a useful method for large-scale
      genotype surveys in Tibet.

PMID- 22465105
TI  - Determining early speech development in children with cochlear implants using the
      ELFRA-2 parental questionnaire.
AB  - OBJECTIVES: Increased early identification of hearing loss has led to infants
      younger than 24 months of age being implanted with cochlear implants. The
      objective of this study was to assess early speech development in children
      implanted with a cochlear implant before 24 months of age using the German
      questionnaire Elternfragebogen fur Risikokinder 2 (ELFRA-2), and to compare these
      results to normative data of the ELFRA-2 in order to determine any performance
      differences. METHODS: Two groups of children were included in this study. The
      first group included 6 children with a mean age at implantation of 11 months
      (range: 8-14 months). These children were tested by their parents or caretakers
      with the ELFRA-2 at the chronological age of 24 months. The second group included
      9 children with a mean age at implantation of 13 months (range: 6-20 months) who
      were tested with the ELFRA-2 after 24 months of cochlear implant use. RESULTS:
      Comparison analyses of children tested with the ELFRA-2 demonstrated a
      statistically significant difference in all ELFRA-2 scales between children with
      cochlear implants (CIs) at the chronological age of 24 months and the norm group
      (productive vocabulary: p=0.002; syntax: p=0.003; and morphology: p<0.001), and
      no significant difference between children with CIs at 24 months of device use
      and the norm group in all scales (productive vocabulary: p=0.335; syntax:
      p=0.965; and morphology: p=0.304). CONCLUSION: Children implanted before 24
      months of age reach a speech production level after 24 months of device use that
      is comparable to that of their normal hearing peers.

PMID- 22465106
TI  - RNA self-ligation: from oligonucleotides to full length ribozymes.
AB  - The RNA-world-theory is one possible explanation of how life on earth has
      evolved. In this context it is of high interest to search for molecular systems,
      capable of self-organization into structures with increasing complexity. We have
      engineered a simple catalytic system in which two short RNA molecules can
      catalyze their own ligation to form a larger RNA construct. The system is based
      on the hairpin ribozyme using a 2',3'-cyclophosphate as activated species for
      ligation. 2',3'-cyclic phosphates can be easily formed and occur in many natural
      systems, thus being superior candidates for activated building blocks in RNA
      world scenarios.

PMID- 22465107
TI  - The minus 10% syndroma.

PMID- 22465108
TI  - Building block organisation of clusters in amylopectin from different structural
      types.
AB  - Clusters of chains consisting of tightly branched units of building blocks were
      isolated from 10 amylopectin samples possessing the 4 types of amylopectin with
      different internal unit chain profiles previously described. It was shown that
      clusters in types 1 and 2 amylopectins are larger than in types 3 and 4, but the
      average cluster size did not correspond to the ratio of short to long chains of
      the amylopectins. The size-distribution of the building blocks, having one or
      several branches, possessed generally only small differences between samples.
      However, the length of the interblock segments followed the type of amylopectin
      structure, so that type 1 amylopectins had shortest and type 4 the longest
      segments. The chains in the clusters were divided into characteristic groups
      probably being involved in the interconnection of two, three, and four - or more 
      building blocks. Long chains were typically found in high amounts in clusters
      from type 4 amylopectins, however, all cluster samples contained long chains. The
      results are discussed in terms of the building block structure of amylopectin, in
      which the blocks together with the interblock segments participate in a branched
      backbone building up the amorphous lamellae inside growth rings of the starch
      granules. In such a model, amylopectins with proportionally less long chains
      (types 1 and 2) possess a more extensively branched backbone compared to those
      with more long chains (types 3 and 4).

PMID- 22465109
TI  - Overcoming multidrug resistance in cancer: 35 years after the discovery of ABCB1.

PMID- 22465110
TI  - Complexity reduction preserving dynamical behavior of biochemical networks.
AB  - The complexity of biochemical systems, stemming from both the large number of
      components and the intricate interactions between these components, may hinder us
      in understanding the behavior of these systems. Therefore, effective methods are
      required to capture their key components and interactions. Here, we present a
      novel and efficient reduction method to simplify mathematical models of
      biochemical systems. Our method is based on the exploration of the so-called
      admissible region, that is the set of parameters for which the mathematical model
      yields some required output. From the shape of the admissible region, parameters
      that are really required in generating the output of the system can be identified
      and hence retained in the model, whereas the rest is removed. To describe the
      idea, first the admissible region of a very small artificial network with only
      three nodes and three parameters is determined. Despite its simplicity, this
      network reveals all the basic ingredients of our reduction method. The method is
      then applied to an epidermal growth factor receptor (EGFR) network model. It
      turns out that only about 34% of the network components are required to yield the
      correct response to the epidermal growth factor (EGF) that was measured in the
      experiments, whereas the rest could be considered as redundant for this purpose.
      Furthermore, it is shown that parameter sensitivity on its own is not a reliable
      tool for model reduction, because highly sensitive parameters are not always
      retained, whereas slightly sensitive parameters are not always removable.

PMID- 22465111
TI  - Stochastic evolutionary dynamics resolve the Traveler's Dilemma.
AB  - Behavior in social dilemmas is often inconsistent with the predictions of
      classical game theory: people (and a wide variety of other organisms) are more
      cooperative than might be expected. Here we consider behavior in one such social
      dilemma, the Traveler's Dilemma, that has received considerable attention in the
      economics literature but is little known among theoretical biologists. The rules
      of the game are as follows. Two players each choose a value between R and M,
      where 0<R<M. If the players choose the same value, both receive that amount. If
      the players choose different values v(1) and v(2), where v(1)<v(2), then the
      player choosing v(1) receives v(1)+R and the player choosing v(2) receives v(1)
      R. While the players would maximize their payoffs by both choosing the largest
      allowed value, M, the Nash equilibrium is to choose the smallest allowed value,
      R. In behavioral experiments, however, people generally choose values much larger
      than the minimum and the deviation from the expected equilibrium decreases with
      R. In this paper, we show that the cooperative behavior observed in the
      Traveler's Dilemma can be explained in an evolutionary framework. We study
      stochastic evolutionary dynamics in finite populations with varying intensity of
      selection and varying mutation rate. We derive analytic results showing that
      strategies choosing high values can be favored when selection is weak. More
      generally, selection favors strategies that choose high values if R is small
      (relative to M) and strategies that choose low values if R is large. Finally, we
      show that a two-parameter model involving the intensity of selection and the
      mutation rate can quantitatively reproduce data that from a Traveler's Dilemma
      experiment. These results demonstrate the power of evolutionary game theory for
      explaining human behavior in contexts that are challenging for standard economic
      game theory.

PMID- 22465112
TI  - Determinants of periodicity in seasonally driven epidemics.
AB  - Seasonality strongly affects the transmission and spatio-temporal dynamics of
      many infectious diseases, and is often an important cause for their recurrence.
      However, there are many open questions regarding the intricate relationship
      between seasonality and the complex dynamics of infectious diseases it gives rise
      to. For example, in the analysis of long-term time-series of childhood diseases,
      it is not clear why there are transitions from regimes with regular annual
      dynamics, to regimes in which epidemics occur every two or more years, and vice
      versa. The classical seasonally-forced SIR epidemic model gives insights into
      these phenomena but due to its intrinsic nonlinearity and complex dynamics, the
      model is rarely amenable to detailed mathematical analysis. Making sensible
      approximations we analytically study the threshold (bifurcation) point of the
      forced SIR model where there is a switch from annual to biennial epidemics. We
      derive, for the first time, a simple equation that predicts the relationship
      between key epidemiological parameters near the bifurcation point. The
      relationship makes clear that, for realistic values of the parameters, the
      transition from biennial to annual dynamics will occur if either the birth-rate
      (MU) or basic reproductive ratio (R(0)) is increased sufficiently, or if the
      strength of seasonality (delta) is reduced sufficiently. These effects are
      confirmed in simulations studies and are also in accord with empirical
      observations. For example, the relationship may explain the correspondence
      between documented transitions in measles epidemics dynamics and concomitant
      changes in demographic and environmental factors.

PMID- 22465113
TI  - Orientation behavior in fish larvae: a missing piece to Hjort's critical period
      hypothesis.
AB  - Larval reef fish possess considerable swimming and sensory abilities, which could
      enable navigation towards settlement habitat from the open ocean. Due to their
      small size and relatively low survival, tagging individual larvae is not a viable
      option, but numerical modeling studies have proven useful for understanding the
      role of orientation throughout ontogeny. Here we combined the theoretical
      framework of the biased correlated random walk model with a very high resolution
      three-dimensional coupled biophysical model to investigate the role of
      orientation behavior in fish larvae. Virtual larvae of the bicolor damselfish
      (Stegastes partitus) were released daily during their peak spawning period from
      two locations in the Florida Keys Reef Tract, a region of complex eddy fields
      bounded by the strong Florida Current. The larvae began orientation behavior
      either before or during flexion, and only larvae that were within a given maximum
      detection distance from the reef were allowed to orient. They were subjected to
      ontogenetic vertical migration, increased their swimming speed during ontogeny,
      and settled on reefs within a flexible window of 24 to 32 days of pelagic
      duration. Early orientation, as well as a large maximum detection distance,
      increased settlement, implying that the early use of large-scale cues increases
      survival. Orientation behavior also increased the number of larvae that settled
      near their home reef, providing evidence that orientation is a mechanism driving
      self-recruitment. This study demonstrates that despite the low swimming abilities
      of the earliest larval stages, orientation during this "critical period" would
      have remarkable demographic consequences.

PMID- 22465114
TI  - Trends in contraceptive patterns and behaviors during a period of fertility
      transition in China: 1988-2006.
AB  - BACKGROUND: This paper explores how contraceptive patterns and behaviors changed
      during the course of China's population transition and a period of low fertility
      from 1988 to 2006. STUDY DESIGN: Based on data from Chinese nationwide surveys of
      family planning and reproductive health undertaken in 1988, 1997, 2001 and 2006,
      this study uses a multinomial logit model to analyze changes in, regional
      differences in and determinants of contraceptive behaviors during this period.
      RESULTS: The overall prevalence of contraceptive use among married women aged 15
      49 years changed little during these 20 years, holding steady at about 90%.
      However, there were notable changes in the method mix: the predominant methods
      used were the long-term methods of the intrauterine device (IUD) and female
      sterilization, and contraceptive use gradually shifted from sterilization to IUDs
      and condoms. There existed a close relationship between contraceptive methods
      used and sociodemographic characteristics. Hans, rural, old and less educated
      women are more likely to use sterilization, while minorities, urban, young and
      educated women are more likely to use IUDs. CONCLUSION: There are marked changes
      in the method mix among different demographic groups during the course of China's
      population transition and a period of low fertility. The findings indicate that
      future works aimed at promoting reproductive health should be diverse among
      different populations.

PMID- 22465115
TI  - Further evidence for lack of negative associations between hormonal contraception
      and mental health.
AB  - BACKGROUND: There is limited and inconsistent information concerning the effects
      of hormonal contraception [oral contraceptives (OCs) and the levonorgestrel
      releasing intrauterine system (LNG-IUS)] on mental health. The aim of this work
      was to further study the association(s) between the use of OCs and the LNG-IUS
      and psychopathology. STUDY DESIGN: Data concerning adult women who participated
      in the national FINRISK Study Surveys in Finland in 1997, 2002 and 2007 were
      analyzed. The associations between the current use, as well as the duration of
      use of OCs and the LNG-IUS vs. mood symptoms, psychological and physical symptoms
      and recent psychiatric diagnoses were tested. RESULTS: A negative association
      between the current use of OCs and Beck Depression Inventory-13 (BDI-13) score
      was found. Some other negative associations, all characterized by a small effect
      size, were detected between current use of OCs and the BDI items feelings of
      dissatisfaction, feelings of uselessness, irritability, lost interest in people
      and lost appetite. Additionally, only weak positive associations were found
      between the duration of OC use and irregular heart rate, insomnia and recent
      anhedonia. No noteworthy associations emerged between current use of the LNG-IUS,
      or its duration, and any of the inquired items. CONCLUSION: The use of hormonal
      contraception is not associated with negative influence on mental health. Current
      OC use seems to be associated with better mood, whereas the associations between
      duration of use of hormonal contraception and mental health effects are not
      clear.

PMID- 22465116
TI  - A combined oral contraceptive containing drospirenone changes neither endothelial
      function nor hemodynamic parameters in healthy young women: a prospective
      clinical trial.
AB  - BACKGROUND: Combined oral contraceptives (COCs) may lead to a rise in
      cardiovascular disease risk, possibly associated with changes in blood pressure
      and endothelial function. STUDY DESIGN: The objective was to evaluate the impact
      of COC containing 20 mcg of ethinylestradiol (EE) and 3 mg of drospirenone (DRSP)
      on the arterial endothelial function, systolic and diastolic blood pressure (SBP
      and DBP , respectively), heart rate (HR), cardiac output (CO) and total
      peripheral resistance (TPR) of healthy young women. Of the 71 women in the study,
      43 were evaluated before the introduction of COC and after 6 months of its use
      (case group) and 28, COC nonusers, were assessed for the same parameters at the
      same time interval (control group). RESULTS: No significant changes in
      endothelium-dependent and endothelium-independent functions or in measures of
      SBP, DBP, HR, CO and TPR caused by COC use were observed in the case group (p>.05
      for all variables) or in the control group. CONCLUSION: These data suggest COC
      with 20 mcg EE and 3 mg DRSP does not alter arterial endothelial function or
      hemodynamic parameters in healthy young women.

PMID- 22465117
TI  - Chlamydia trachomatis Tarp cooperates with the Arp2/3 complex to increase the
      rate of actin polymerization.
AB  - Actin polymerization is required for Chlamydia trachomatis entry into
      nonphagocytic host cells. Host and chlamydial actin nucleators are essential for
      internalization of chlamydiae by eukaryotic cells. The host cell Arp2/3 complex
      and the chlamydial translocated actin recruiting phosphoprotein (Tarp) are both
      required for entry. Tarp and the Arp2/3 complex exhibit unique actin
      polymerization kinetics individually, but the molecular details of how these two
      actin nucleators cooperate to promote bacterial entry is not understood. In this
      study we provide biochemical evidence that the two actin nucleators act
      synergistically by co-opting the unique attributes of each to enhance the
      dynamics of actin filament formation. This process is independent of Tarp
      phosphorylation. We further demonstrate that Tarp colocalization with actin
      filaments is independent of the Tarp phosphorylation domain. The results are
      consistent with a model in which chlamydial and host cell actin nucleators
      cooperate to increase the rate of actin filament formation.

PMID- 22465118
TI  - Glucose and insulin induce Ca2+ signaling in nesfatin-1 neurons in the
      hypothalamic paraventricular nucleus.
AB  - Nucleobindin-2 derived nesfatin-1 in the hypothalamic paraventricular nucleus
      (PVN) plays a role in inhibition of feeding. The neural pathways downstream of
      PVN nesfatin-1 have been extensively investigated. However, regulation of the PVN
      nesfatin-1 neurons remains unclear. Since starvation decreases and refeeding
      stimulates nesfatin-1 expression specifically in the PVN, this study aimed to
      clarify direct effects of meal-evoked metabolic factors, glucose and insulin, on
      PVN nesfatin-1 neurons. High glucose (10mM) and insulin (10(-13)M) increased
      cytosolic calcium concentration ([Ca(2+)](i)) in 55 of 331 (16.6%) and 32 of 249
      (12.9%) PVN neurons, respectively. Post [Ca(2+)](i) measurement
      immunocytochemistry identified that 58.2% of glucose-responsive and 62.5% of
      insulin-responsive neurons were immunoreactive to nesfatin-1. Furthermore, a
      fraction of the glucose-responsive nesfatin-1 neurons also responded to insulin,
      and vice versa. Some of the neurons that responded to neither glucose nor insulin
      were recruited to [Ca(2+)](i) increases by glucose and insulin in combination.
      Our data demonstrate that glucose and insulin directly interact with and increase
      [Ca(2+)](i) in nesfatin-1 neurons in the PVN, and that the nesfatin-1 neuron is
      the primary target for them in the PVN. The results suggest that high glucose-
      and insulin-induced activation of PVN nesfatin-1 neurons serves as a mechanism
      through which meal ingestion stimulates nesfatin-1 neurons in the PVN and thereby
      produces satiety.

PMID- 22465119
TI  - Divergent effects of 17-beta-estradiol on human vascular smooth muscle and
      endothelial cell function diminishes TNF-alpha-induced neointima formation.
AB  - Coronary heart disease (CHD) is a condition characterized by increased levels of
      proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). TNF
      alpha can induce vascular endothelial cell (EC) and smooth muscle cell (SMC)
      dysfunction, central events in development of neointimal lesions. The reduced
      incidence of CHD in young women is believed to be due to the protective effects
      of estradiol (E2). We therefore investigated the effects of TNF-alpha on human
      neointima formation and SMC/EC functions and any modulatory effects of E2.
      Saphenous vein (SV) segments were cultured in the presence of TNF-alpha (10
      ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented
      by incubation with TNF-alpha, an effect that was abolished by co-culture with E2.
      TNF-alpha increased SV-SMC proliferation in a concentration-dependent manner that
      was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all
      concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations
      (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF
      alpha alone. SV-EC migration was significantly impaired by TNF-alpha (42% of
      control), and co-culture with E2 partially restored the ability of SV-EC to
      migrate and repair the wound. In contrast, TNF-alpha increased SV-SMC migration
      by 1.7-fold, an effect that was completely reversed by co-incubation with E2.
      Finally, TNF-alpha potently induced ICAM-1 and VCAM-1 expression in both SV-EC
      and SV-SMC. However there was no modulation by E2 in either cell-type. In
      conclusion, TNF-alpha induced SV neointima formation, increased SMC proliferation
      and migration, impaired SV-EC migration and increased expression of adhesion
      molecules. E2 exerted distinct cell-type and function-specific modulation, the
      mechanisms underlying which are worthy of further detailed study.

PMID- 22465120
TI  - Cyclin A regulates a cell-cycle-dependent expression of CKAP2 through
      phosphorylation of Sp1.
AB  - CKAP2 plays crucial roles in proper chromosome segregation and maintaining
      genomic stability. CKAP2 protein showed cell-cycle-dependent expression, which
      reached a maximum level at the G2/M phase and disappeared at the onset of G1
      phase. To elucidate the mechanisms underlying cell cycle-dependent expression of
      CKAP2, we cloned and analyzed the human CKAP2 promoter. The upstream 115-bp
      region from the transcription start site was sufficient for minimal CKAP2
      promoter activity. We identified 2 regulatory sequences; a CHR (-110 to -104 bp)
      and a GC box (-41 to -32 bp). We confirmed Sp1 bound to the GC box using a
      supershift assay and a ChIP assay. Mutation in the GC box resulted in a near
      complete loss of CKAP2 promoter activity while mutation in the CHR decreased the
      promoter activity by 50%. The CHR mutation showed enhanced activity at the G1/S
      phase, but still retained cyclic activity. The Chromatin IP revealed that the
      amount of Sp1 bound to the GC box gradually increased and reached a maximum level
      at the G2/M phase. The amount of Sp1 bound to the GC box was greatly reduced when
      Cyclin A was depleted, which was restored by adding Cyclin A/Cdk2 complex back
      into the nuclear extracts. Together, we concluded that the GC box was responsible
      for the cyclic activity of human CKAP2 promoter through the phosphorylation of
      Sp1, possibly by Cyclin A/Cdk complex.

PMID- 22465121
TI  - Pivotal role of activating transcription factor 6alpha in myocardial adaptation
      to chronic hypoxia.
AB  - Hypoxic states are generally associated with cardiovascular disease. Adaptation
      to chronic hypoxia is one well-defined means of improving cardiac tolerance to
      certain kinds of stresses. However, the details of the mechanisms underlying
      myocardial adaptation to chronic hypoxia are still poorly understood. Hypoxia
      stresses the endoplasmic reticulum and activates unfolded protein response.
      However, the behavior of individual signaling pathways can vary markedly over
      time. By examining myocardial samples from patients with cyanotic congenital
      cardiac defects, we detected endoplasmic reticulum stress and found that, out of
      all the components of the unfolded protein response, only activating
      transcription factor 6alpha limb was activated in cyanotic patients. The
      activation of activating transcription factor 6alpha and expression of glucose
      regulated protein 78 were notably induced in cardiac myocytes cultured for
      prolonged hypoxia (1% O(2) for 48 h). When the activation of activating
      transcription factor 6alpha under prolonged hypoxia was blocked by chemical
      inhibitor Brefeldin A, the rate of apoptosis among cardiac myocytes increased and
      levels of cleaved caspase 3 and cleaved poly ADP ribose polymerase also increased
      significantly. After the expression of activating transcription factor 6alpha was
      knocked down, the activity of cardiac myocytes under prolonged hypoxia decreased
      and the phosphorylation of c-Jun NH2-terminal kinases increased during the re
      oxygenation process (after 72 h of hypoxia). Together, these results indicate
      that activating transcription factor 6alpha plays a pivotal role in myocardial
      adaptation to chronic hypoxia and that the activation of activating transcription
      factor 6alpha is one possible mechanism of myocardial preconditioning.

PMID- 22465122
TI  - The MR arthrographic anatomy of the biceps labral insertion and its morphological
      significance with labral tears in patients with shoulder instability.
AB  - INTRODUCTION: Most of the fibres of the long head of biceps tendon attach on the
      superior labrum just posterior to the supraglenoid tubercle. AIM: Our hypothesis
      was that posteriorly attached biceps tendons predispose to posterior superior
      labral tears and SLAP lesions. METHODS AND MATERIALS: A prospective analysis of
      all MR shoulder arthrograms for shoulder instability referred from the shoulder
      specialist clinics, performed during a one year period were reviewed by two
      independent observers who were blinded to clinical history. The biceps attachment
      was classified into four groups according to the method described in an earlier
      cadaveric study into four groups; posterior-type 1, predominantly posterior-type
      2, equal contributions to both anterior and posterior labrum-type 3 and
      predominantly anterior labral attachment-type 4. Data was analysed using Kappa
      statistics and Fischer's exact test. RESULTS: 48 patients (33 males and 15
      females) were included in this study with a mean age of 32 years. Majority, 22
      patients (46%) had a type 1 attachment of the biceps on the superior labrum.
      There was moderate intra-observer and good interobserver agreement with a Kappa
      of 0.58 and 0.63 respectively. There was a significant association between a type
      2 attachment and posterior tears (p<=0.04) and also between a type 2 attachment
      and SLAP tears (p<=0.04). CONCLUSION: Our results suggest that variation in
      anatomy of biceps origin influences the type of labral tears that occur in
      patients with shoulder instability. The importance of these findings could
      influence selection of individuals in throwing sports like cricket and baseball.

PMID- 22465123
TI  - CT analysis of the effect of pirfenidone in patients with idiopathic pulmonary
      fibrosis.
AB  - PURPOSE: Pirfenidone is a new, anti-fibrotic drug used for the treatment of
      idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the
      utility of computed tomography (CT) in the imaging assessment of the response to
      pirfenidone therapy. MATERIALS AND METHODS: Subjects were 78 patients with IPF
      who underwent CT on two occasions with one-year interval (38 consecutive patients
      treated with pirfenidone and 40 age-matched control). Changes in the fibrous
      lesion on sequential CTs were assessed as visual score by two radiologists. We
      measured the volume and change per year of fibrous pattern (F-pattern)
      quantitatively using a computer-aided system on sequential CTs. RESULTS: The
      baseline vital capacity (%pred VC) was 74.0 +/- 14.0% in the pirfenidone group
      and 74.6 +/- 16.6% in controls (p=NS). Deterioration of respiratory status was
      defined as 10% or greater decline in %pred VC value after 12-month treatment. A
      significantly larger proportion of pirfenidone-treated patients showed stable
      respiratory status (21 of 38, 65.6%) than the control (15 of 40, 37.5%). The
      change in fibrous lesion was significantly smaller in the pirfenidone group than
      the control in both of visual score (p=0.006) and computer analysis (p<0.001).
      The decline in VC correlated significantly with the increase in fibrotic lesion
      (p<0.001). CONCLUSION: CT can be used to assess pirfenidone-induced slowing of
      progression of pulmonary fibrosis.

PMID- 22465124
TI  - Pitfalls in osteoarticular imaging: how to distinguish bone infection from
      tumour?
AB  - In this article examining pitfalls in osteoarticular imaging we examine the
      differential diagnosis of osteomyelitis from bone tumours. We describe the
      different features which differentiate these two types of disease in radiology
      and CT and MRI scanning.

PMID- 22465126
TI  - Delta changes for optimizing clinical specificity and 60-day risk of adverse
      events in patients presenting with symptoms suggestive of acute coronary syndrome
      utilizing the ADVIA Centaur TnI-Ultra assay.
AB  - OBJECTIVES: We determined diagnostic accuracy and risk stratification using delta
      changes for the cardiac troponin I (cTnI) Centaur Ultra assay for ruling out
      acute myocardial infarction (AMI) and for risk prediction of adverse events in
      patients with symptoms of acute coronary syndrome. DESIGN AND METHODS: cTnI was
      measured on admission and 6-24 h in 371 patients. Optimal deltas (percent change,
      absolute value of percent change, change, absolute value of change) were
      determined from ROC curve analysis. Risk stratification was performed for cardiac
      events and death within 60 days. RESULTS: AMI during hospitalization occurred in
      49 patients and endpoints in 11 patients. Diagnostic accuracy by ROC curve was
      optimal (0.96) using the absolute value of change delta. Diagnostic specificities
      utilizing the 99th percentile (40 ng/L) for admission and follow-up samples were
      84% and 81%, compared to: [90% percent change delta] 89.7%; [66.7% absolute value
      of percent change delta] 85.5%, [217 ng/L change delta] 99.0% and [55 ng/L
      absolute value of change delta] 93.7%. All four delta values showed substantially
      greater risk when the initial cTn value was normal. CONCLUSIONS: Utilizing delta
      cTnI values improves clinical specificity, diagnostic accuracy and risk
      assessment in patients presenting with symptoms of ACS.

PMID- 22465127
TI  - Clinical-chemistry laboratory relevant hemolysis is unlikely to compromise human
      plasma concentration of free asymmetric dimethylarginine (ADMA).

PMID- 22465125
TI  - Emerging roles for lysophosphatidylserine in resolution of inflammation.
AB  - Despite overlapping structural aspects with other phospholipids,
      lysophosphatidylserine (lysoPS), the monoacyl derivative of phosphatidylserine
      (diacylPS), appears to exert unique signaling characteristics important in both
      the early stages of initiating acute inflammation and in the orchestration of its
      resolution. LysoPS has long been known as a signaling phospholipid in mast cell
      biology, markedly enhancing stimulated histamine release and eicosanoid
      production. More recently, there has been a resurgence of interest in lysoPS as
      new roles in the promotion of phagocytosis of apoptotic cells, so-called
      efferocytosis, and resolution of inflammation have been identified. With regard
      to the latter, lysoPS generated in/on activated or aged apoptotic neutrophils
      enhances their clearance by macrophages via signaling through the macrophage G
      protein coupled receptor G2A. In macrophages, this early acting pathway results
      in PKA-dependent augmentation of Rac1 activity via increased production of PGE2
      and cAMP. As such, macrophages stimulated with lysoPS demonstrate significantly
      increased efferocytic capacity necessary to clear large numbers of recruited
      neutrophils typical of acute inflammation. Given that clearance of these cells is
      critical for restoration of tissue function, lysoPS, as a pro-resolving lipid
      mediator, is hypothesized to play a key role in promoting timely resolution of
      inflammation. This article will review our current knowledge of lysoPS biology
      including receptor signaling and mechanisms of generation as well as summarize
      the more recent evidence of its expanding roles in inflammation.

PMID- 22465128
TI  - Neuronal glycosylation differentials in normal, injured and chondroitinase
      treated environments.
AB  - Glycosylation is found ubiquitously throughout the central nervous system (CNS).
      Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily
      substituted with glycosaminoglycans (GAGs) and are found in the extracellular
      matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is
      inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial
      scar, including NG2, and these CSPGs are key inhibitory molecules of axonal
      regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the
      inhibitory nature of NG2. A gene expression dataset was mined in silico to verify
      differentially regulated glycosylation-related genes in neurons after spinal cord
      injury and identify potential targets for further investigation. To establish the
      glycosylation differential of neurons that grow in a healthy, inhibitory and
      ChABC-treated environment, we established an indirect co-culture system where
      PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which
      overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days
      culture, lectin cytochemistry of the neurons was performed using five
      fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually alpha-(2,6)
      linked sialylation scarcely occurs in the CNS but this motif was observed on the
      neurons in the injured environment only at day 8. Treatment with ChABC was
      successful in returning neuronal glycosylation to normal conditions at all
      timepoints for MAA, PNA and SNA-I staining, and by day 8 in the case of WFA. This
      study demonstrated neuronal cell surface glycosylation changes in an inhibitory
      environment and indicated a return to normal glycosylation after treatment with
      ChABC, which may be promising for identifying potential therapies for neuronal
      regeneration strategies.

PMID- 22465129
TI  - In vitro reprogramming of rat bone marrow-derived mesenchymal stem cells into
      insulin-producing cells by genetically manipulating negative and positive
      regulators.
AB  - Islet cell replacement therapy represents the most promising approach for the
      cure of type 1 diabetes if autoimmunity to beta cells is under control. However,
      this potential is limited by a shortage of pancreas donors. To address the donor
      shortage problem, we determined whether bone marrow-derived mesenchymal stem
      cells (bmMSCs) can be directly reprogrammed to islet lineages by simultaneously
      forced suppression and over-expression of key regulator genes that play critical
      roles during pancreas development. Here, we report that rat bmMSCs were converted
      in vitro into insulin-producing cells by suppressing two-repressor genes
      repressor element-1 silencing transcription factor/neuronal restrictive silencing
      factor (Rest/Nrsf) and sonic hedgehog (Shh) and by over-expressing pancreas and
      duodenal transcription factor 1 (Pdx1). The reprogrammed bmMSCs expressed both
      genes and proteins specific for islet cells. These converted cells were capable
      of releasing insulin in a glucose-responsive manner. Our study suggests that
      bmMSCs may ultimately be reprogrammed to functional insulin-secreting cells.

PMID- 22465130
TI  - 18beta-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates
      lipolysis.
AB  - 18beta-Glycyrrhetinic acid (18beta-GA) obtained from the herb liquorice has
      various pharmacological properties including anti-inflammatory and anti-bacterial
      activities. However, potential biological anti-obesity activities are unclear. In
      this study, novel biological activities of 18beta-GA in the adipogenesis of 3T3
      L1 preadipocytes and in lipolysis of differentiated adipocytes were identified.
      Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis,
      using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to
      induce differentiation. The amount of lipid droplet accumulation was determined
      by an AdipoRed assay. The expression of several adipogenic transcription factors
      and enzymes was investigated using real-time reverse transcriptase-polymerase
      chain reaction (RT-PCR) and Western blotting. 18beta-GA dose-dependently (1-40
      MUM) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3
      L1 preadipocytes, 10 MUM of 18beta-GA down-regulated the transcriptional levels
      of the peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding
      protein alpha and adiponectin, which are markers of adipogenic differentiation
      via Akt phosphorylation. Also, in differentiated adipocytes, 18beta-GA increased
      the level of glycerol release and up-regulated the mRNA of hormone-sensitive
      lipase, adipose TG lipase and perilipin, as well as the phosphorylation of
      hormone-sensitive lipase at Serine 563. The results indicate that 18beta-GA
      alters fat mass by directly affecting adipogenesis in maturing preadipocytes and
      lipolysis in matured adipocytes. Thus, 18beta-GA may be useful for the treatment
      of obesity.

PMID- 22465131
TI  - Wnt3a promotes melanin synthesis of mouse hair follicle melanocytes.
AB  - Although the importance of Wnt3a in melanocyte development has been well
      recognized, the effect of Wnt3a in normal HF melanocytes has not been clearly
      elucidated yet. Thus, we sought to examine the presence and location of Wnt3a in
      HF during hair cycle. By using melanocyte-targeted Dct-LacZ transgenic mice, we
      found that Wnt3a signaling is activated in mouse HF melanocytes during anagen of
      hair cycle. To further explore the potential functions of Wnt3a in mouse
      melanocytes, we infected melan-a cells with AdWnt3a to serve as the production
      source of Wnt3a protein. We demonstrated that Wnt3a promoted melanogenesis
      through upregulation of MITF and its downstream genes, tyrosinase and TRP1, in
      melanocytes. In vivo, AdWnt3a rescued the effects of AdsimMITF on HF melanocytes
      and promoted melanin synthesis. Our results suggest that Wnt3a plays an important
      role in mouse HF melanocytes homeostasis.

PMID- 22465132
TI  - Solving the puzzles of cutin and suberin polymer biosynthesis.
AB  - Cutin and suberin are insoluble lipid polymers that provide critical barrier
      functions to the cell wall of certain plant tissues, including the epidermis,
      endodermis and periderm. Genes that are specific to the biosynthesis of cutins
      and/or aliphatic suberins have been identified, mainly in Arabidopsis thaliana.
      They notably encode acyltransferases, oxidases and transporters, which may have
      either well-defined or more debatable biochemical functions. However, despite
      these advances, important aspects of cutin and suberin synthesis remain obscure.
      Central questions include whether fatty acyl monomers or oligomers are exported,
      and the extent of extracellular assembly and attachment to the cell wall. These
      issues are reviewed. Greater emphasis on chemistry and biochemistry will be
      required to solve these unknowns and link structure with function.

PMID- 22465133
TI  - Plant-bacterial pathogen interactions mediated by type III effectors.
AB  - Effectors secreted by the bacterial type III system play a central role in the
      interaction between Gram-negative bacterial pathogens and their host plants.
      Recent advances in the effector studies have helped cementing several key
      concepts concerning bacterial pathogenesis, plant immunity, and plant-pathogen co
      evolution. Type III effectors use a variety of biochemical mechanisms to target
      specific host proteins or DNA for pathogenesis. The identifications of their host
      targets led to the identification of novel components of plant innate immune
      system. Key modules of plant immune signaling pathways such as immune receptor
      complexes and MAPK cascades have emerged as a major battle ground for host
      pathogen adaptation. These modules are attacked by multiple type III effectors,
      and some components of these modules have evolved to actively sense the effectors
      and trigger immunity.

PMID- 22465134
TI  - Baroreflex modulation during sleep and in obstructive sleep apnea syndrome.
AB  - This review focuses on the complex integration between cardiovascular reflexes
      and central autonomic influences controlling physiological sleep-dependent
      changes in arterial blood pressure and heart rate. A brief introduction on the
      anatomic and functional organization of the arterial baroreflex and the methods
      available to assess its function in humans is followed by an analysis of the
      functional interaction between autonomic nervous system and sleep mechanisms at
      the highest levels of brain organization. An insight into these interactions is
      important to shed light on the physiopathology of the most frequent complications
      of obstructive sleep apnea syndrome, such as sustained arterial hypertension, and
      excessive daytime sleepiness.

PMID- 22465135
TI  - [Catastrophic antiphospholipid syndrome].

PMID- 22465136
TI  - How expectations shape pain.
AB  - Pain is highly modifiable by psychological factors, including expectations.
      However, pain is a complex phenomenon, and expectations may work by influencing
      any number of processes that underlie the construction of pain. Neuroimaging has
      begun to provide a window into these brain processes, and how expectations
      influence them. In this article, we review findings regarding expectancy effects
      on brain markers of nociception and how expectations lead to changes in
      subjective pain. We address both expectations about treatments (placebo analgesia
      and nocebo effects) and expectations about the environment (e.g. expectations
      about pain itself). The body of work reviewed indicates that expectancies shape
      pain-intensity processing in the central nervous system, with strong effects on
      nociceptive portions of insula, cingulate and thalamus. Expectancy effects on
      subjective experience are driven by responses in these regions as well as regions
      less reliably activated by changes in noxious input, including the dorsolateral
      prefrontal cortex and the orbitofrontal cortex. Thus, multiple systems are likely
      to interact and mediate the pain-modulatory effects of expectancies. Finally, we
      address open questions regarding the psychological processes likely to play an
      intervening role in expectancy effects on pain.

PMID- 22465137
TI  - Spatiotemporal frequency characteristics of cerebral oscillations during the
      perception of fundamental frequency contour changes in one-syllable intonation.
AB  - Accurate perception of fundamental frequency (F0) contour changes in the human
      voice is important for understanding a speaker's intonation, and consequently
      also his/her attitude. In this study, we investigated the neural processes
      involved in the perception of F0 contour changes in the Japanese one-syllable
      interjection "ne" in 21 native-Japanese listeners. A passive oddball paradigm was
      applied in which "ne" with a high falling F0 contour, used when urging a reaction
      from the listener, was randomly presented as a rare deviant among a frequent "ne"
      syllable with a flat F0 contour (i.e., meaningless intonation). We applied an
      adaptive spatial filtering method to the neuromagnetic time course recorded by
      whole-head magnetoencephalography (MEG) and estimated the spatiotemporal
      frequency dynamics of event-related cerebral oscillatory changes in the oddball
      paradigm. Our results demonstrated a significant elevation of beta band event
      related desynchronization (ERD) in the right temporal and frontal areas, in time
      windows from 100 to 300 and from 300 to 500 ms after the onset of deviant stimuli
      (high falling F0 contour). This is the first study to reveal detailed
      spatiotemporal frequency characteristics of cerebral oscillations during the
      perception of intonational (not lexical) F0 contour changes in the human voice.
      The results further confirmed that the right hemisphere is associated with
      perception of intonational F0 contour information in the human voice, especially
      in early time windows.

PMID- 22465138
TI  - Association study of SCARB2 rs6812193 polymorphism with Parkinson's disease in
      Han Chinese.
AB  - Recently, a nucleotide polymorphism rs6812193 near SCARB2 was found to be
      significantly associated with Parkinson's disease (PD) in populations of European
      ancestry. Herein, we conducted a case-control study with attempt to further
      evaluate the association between SNP rs6812193 and PD in a Chinese population
      from mainland China. rs6812193 was genotyped by PCR-RFLP technique in 449 PD
      patients and 452 controls in a Chinese population. In our study, we did not
      detect statistically significant differences between cases and controls in terms
      of both allele and genotype distribution of the rs6812193 polymorphism (P=0.97
      and P=0.77, respectively), even after stratification by age at onset. Our data do
      not support the association of SNP rs6812193 with PD in Han Chinese of mainland
      China.

PMID- 22465139
TI  - Strategical implications of aneurysmal cranial nerve compression.
AB  - Intracranial aneurysms may manifest clinically by inducing neurological symptoms,
      including cranial nerve dysfunction. In unruptured aneurysms, this may result
      from mass effect and the pulsation of the sac. Aneurysm rupture and sudden
      expansion of a pseudo-sac may precipitate the appearance of cranial nerve
      deficits. Symptomatic aneurysms should be treated. Surgery reduces mass effect
      and arterial pulsations, and removes clot after rupture. Endovascular treatment
      decreases pulsatility of the sac. Recovery has been reported after both
      treatments. It appears more reproducible after surgery, but the data of current
      literature remains weak. The possible advantage of surgery is an argument among
      others that must be considered in the choice of the most adequate therapeutic
      approach.

PMID- 22465140
TI  - [Mechanisms of action of high-frequency deep brain stimulation. A review of the
      literature and current concepts].
AB  - High-frequency deep brain stimulation (HF-DBS) has become a widely used
      therapeutic method in the field of movement disorders for the treatment of
      Parkinson's disease, essential tremor or dystonia. New targets and indications
      are under evaluation in several other conditions such as cluster headache,
      obesity, epilepsy or psychiatric diseases (depression, OCD). However, the
      mechanisms of action of HF-DBS remain poorly understood. Herein we present a
      review of the literature and our current view of the question. The first part
      deals with the effects of stimulation itself on the different parts of the neuron
      and tries to answer the question of what is actually stimulated by DBS (cell
      bodies, dendrites or axons). The second part is devoted to the ortho- and
      antidromic effects of the stimulation. The third part more specifically focuses
      on the case of subthalamic nucleus stimulation. The target axons in the
      subthalamic area are discussed in the light of recent optogenetic studies. In
      conclusion, HF-DBS leads to a kind of functional deafferentation of the
      stimulated structure and to the modulation of cortical activity (both ortho and
      antidromically). Which effects are relevant to the therapeutic effects of DBS is
      still unclear. Further investigations are required especially regarding the
      corticosubthalamic pathways.

PMID- 22465141
TI  - RCTs in determining treatment indications for intracranial aneurysms: What can we
      learn from history?
AB  - BACKGROUND AND PURPOSE: Many important issues regarding the management of
      intracranial aneurysms remain controversial. We review the role played by
      randomized trials in the determination of the best management of intracranial
      aneurysms in the early era of surgical clipping. METHODS: Landmark trials and
      cooperative studies are analyzed and results summarized in a narrative review.
      RESULTS: The most convincing evidence in favour of surgical management of
      ruptured intracranial aneurysms came from early randomized trials conducted from
      the 1950s to 1970s. Large historical observational studies, performed between the
      1970s and 2000, aiming to guide clinical practice, provided only statistical
      associations mixed with confounding variables. After the early RCTs, the next
      important gain in reliable knowledge occurred with completion of the ISAT trial,
      more than 25 years later. CONCLUSION: The pioneering neurosurgeons of early
      trials can provide the inspiration necessary to make real progress in
      understanding the best clinical management of intracranial aneurysms.

PMID- 22465142
TI  - Surgical strategies for aneurysms deemed unclippable and uncoilable.
AB  - Although most cerebral aneurysms can nowadays be successfully treated either by
      standard clipping or sole coiling, a subset of aneurysms may not be amenable to
      standard clipping or coiling and require alternative treatment options. Surgical
      options, other than clipping and/or endovascular options other than sole coiling,
      may be the optimal treatment plan for some complex aneurysms. Surgical strategies
      for such complex aneurysms include parent artery occlusion, revascularization
      procedures and flow redirection. In this article, we review which factors are
      predictive of failure of conventional aneurysm treatment options; summarize key
      information needed to orient treatment decision; and discuss surgical options for
      unclippable and uncoilable aneurysms.

PMID- 22465143
TI  - Haptoglobin genotype and its role in determining heme-iron mediated vascular
      disease.
AB  - Haptoglobin (Hp) is a hemoglobin (Hb) binding protein whose major function is to
      prevent heme-iron mediated oxidation. The polymorphic nature of the Hp gene
      results in varying levels of antioxidant function associated with the protein
      products. Multiple clinical studies have now determined that the Hp 2-2 genotype
      is associated with an increased risk of developing vascular complications in
      patients suffering from diabetes. The mechanism for this phenomenon is a decrease
      in antioxidant capability associated with the Hp 2-2 protein. Specifically, heme
      iron associated with the Hp2-2/Hb complex is more redox active than other Hp type
      complexes and has been shown in a number of systems to lead to increased levels
      of oxidative stress in the form of oxidized lipids and decreased lipoprotein
      function. In addition, Hp 2-2/Hb complexes are cleared less efficiently from the
      circulation, leading to a buildup of iron in the plasma and in tissues. Recent
      analyses from clinical studies utilizing vitamin E treatment have shown
      beneficial results specifically in the diabetic Hp 2-2 genotype population. The
      use of vitamin E in the treatment of Hp 2-2 diabetics has the potential to
      greatly reduce medical costs and improve quality of life in the ever-growing
      diabetic population.

PMID- 22465144
TI  - The cannabinoid receptor type 2 Q63R variant increases the risk of celiac
      disease: implication for a novel molecular biomarker and future therapeutic
      intervention.
AB  - Celiac disease (CD) is a chronic inflammatory disease of the small bowel that
      occurs with the ingestion of gluten, found in several grains products. Although
      HLA-DQ2 variant is required for the gluten-derived peptide gliadin presentation
      by antigen-presenting cells to T-cells, non-HLA genetic factors account for the
      majority of heritable risk. Several genome-wide association studies have
      identified susceptibility loci for CD on chromosome 1. Cells of the immune system
      express the cannabinoid receptor type 2 (CB2), a plasma-membrane receptor
      activated by both endogenous and exogenous cannabinoids. Consistent data evidence
      that CB2 is linked to a variety of immune functional events and that, in the
      course of an inflammatory process, an increased number of receptors becomes
      available for activation. The cannabinoid receptor type 2 gene (CNR2; GeneID1269)
      maps on 1p36.11. In order to investigate the possible involvement of CB2 in CD
      establishment, immunohistochemistry toward CB2 receptor and CD4+ cells in small
      bowel biopsies from celiac children and association analysis, through TaqMan
      assay, of a CNR2 common missense variant, rs35761398 (CAA/CGG), resulting in the
      aminoacidic substitution of Glutamine at codon 63 with Arginine (Q63R), in a
      cohort of 327 South Italian children have been performed. We observed in this
      study that CB2 is up-regulated in CD small bowel biopsies and CNR2 rs35761398 is
      significantly associated with CD (chi(2) = 37.064; d.f. 1; p = 1.14 * 10(-9)).
      Our findings suggest a role of CB2 in CD. The Q63R variant, increasing more than
      six-fold the risk for CD susceptibility, might eventually represent a novel
      molecular biomarker for CD risk stratification. Indeed, we provide here further
      evidence that CB2 receptor plays a critical role in autoimmunity susceptibility
      and indicates that it represents a molecular target to pharmacologically modulate
      the immune components in CD.

PMID- 22465145
TI  - Modulatory effects of Kaempferia parviflora extract on mouse hepatic cytochrome
      P450 enzymes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia parviflora is a herbal plant, the
      extracts of which are commonly used as alternative medicines. It widely uses as
      aphrodisiac, anti-inflammation, anti-microbacterial, and anti-peptic ulcer. AIM
      OF THE STUDY: In order to obtain an effective utilization and safety of the herb,
      the influence of Kaempferia parviflora on hepatic CYP450 metabolizing enzymes
      including CYP1A1, CYP1A2, CYP2B, CYP2E1, and CYP3A was investigated. MATERIALS
      AND METHODS: The impact of Kaempferia parviflora on CYP450 both in vitro and in
      vivo was examined by using ethoxyresorufin O-dealkylation, methoxyresorufin O
      dealkylation, pentoxyresorufin O-dealkylation, p-nitrophenol hydroxylation, and
      erythromycin N-demethylation assays, respectively. RESULTS: In vitro studies
      using non-induced mouse hepatic microsomes in the presence or absence of
      Kaempferia parviflora extract showed that Kaempferia parviflora extract altered
      CYP1A1, CYP1A2, CYP2B, and CYP2E1 activities by non-competitive, mixed
      competitive, competitive, and uncompetitive mechanisms, respectively. Among these
      enzymes, CYP1A2 was affected by Kaempferia parviflora based on the highest value
      of V(max) (15.276+/-0.206 nmol/min) and lowest of K(i) value (0.008+/-0.002
      MUg/ml). In addition, the plant extract also modulated CYP2B activity based on
      the low K(m) value (1.599+/-0.147 pmol). For in vivo studies, mice were orally
      treated with 250 mg/kg of Kaempferia parviflora extract for 7, 14, and 21 days.
      The results demonstrated that Kaempferia parviflora extract significantly induced
      CYP1A1, CYP1A2 enzyme activities following short-term treatment. CYP2B enzyme
      activities were markedly increased all Kaempferia parviflora extract treatment
      timepoints, whereas Kaempferia parviflora extract significantly enhanced CYP2E1
      activity only after long-term treatment. However, Kaempferia parviflora extract
      did not affect the CYP3A enzyme activity. CONCLUSIONS: Kaempferia parviflora
      extract modulated several CYP450 enzyme activities, thus, its utilization with
      drugs or other herbs should raise concern for potential drug-herb interactions.

PMID- 22465146
TI  - Antitumor and immunomodulatory effects of Justicia spicigera Schltdl
      (Acanthaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are an important source of
      antitumor compounds. This study evaluated the acute toxicity in vitro and in
      vivo, as well as the cytotoxic, antitumor and immunomodulatory effects of
      ethanolic extracts of Justicia spicigera leaves (JSE). MATERIALS AND METHODS: The
      in vitro and in vivo toxicity of JSE was evaluated with comet assay in peripheral
      blood mononuclear cells (PBMC) and acute toxicity in mice, according to the Lorke
      procedure, respectively. The apoptotic effect of JSE on human cancer cells and
      human noncancerous cells was evaluated using flow cytometry with annexin-Alexa
      488/propidium iodide. Also, different doses of JSE were injected
      intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 18
      days. The growth and weight of tumors were measured. The in vitro
      immunomodulatory effects of JSE were evaluated estimating the effects of JSE on
      the phagocytosis of the yeast Saccharomyces cerevisiae, NO production and
      H(2)O(2) release in macrophages, as well as the proliferation of splenocytes and
      NK activity. RESULTS: The comet assay showed that only JSE tested at 200 and 1000
      MUg/ml induced a significantly DNA damage in PBMC, compared to untreated cells,
      whereas the LD(50) was >5000 mg/kg by intraperitoneal route (i.p.) and by oral
      route. JSE showed pro-apoptotic (Annexin/PI) effects by 35% against HeLa cells,
      but lack toxic effects against human normal cells. JSE administrated at 10, 50
      and 100 mg/kg i.p. inhibited the tumor growth by 28%, 41% and 53%, respectively,
      in mice bearing HeLa tumor. JSE stimulated, in a concentration dependent manner,
      the phagocytosis of Saccharomyces cerevisiae yeasts, the NO production and
      H(2)O(2) release by human differentiated macrophages. In addition, JSE stimulated
      the proliferation of murine splenocytes and induced the NK cell activity.
      CONCLUSION: Justicia spicigera shows low toxic effects in vitro and in vivo,
      exerts apoptotic effects on HeLa cells, has antitumor effects in mice bearing
      HeLa tumor and induces immunomodulatory activities in vitro.

PMID- 22465147
TI  - Synthetic biology: an EFB microbial physiology section initiative.

PMID- 22465148
TI  - Characteristics common to a cytokine family spanning five orders of insects.
AB  - Growth-blocking peptide (GBP) is a member of an insect cytokine family with
      diverse functions including growth and immunity controls. Members of this
      cytokine family have been reported in 15 species of Lepidoptera, and we have
      recently identified GBP-like peptides in Diptera such as Lucilia cuprina and
      Drosophila melanogaster, indicating that this peptide family is not specific to
      Lepidoptera. In order to extend our knowledge of this peptide family, we purified
      the same family peptide from one of the tenebrionids, Zophobas atratus,(1)
      isolated its cDNA, and sequenced it. The Z. atratus GBP sequence together with
      reported sequence data of peptides from the same family enabled us to perform
      BLAST searches against EST and genome databases of several insect species
      including Coleoptera, Diptera, Hymenoptera, and Hemiptera and identify homologous
      peptide genes. Here we report conserved structural features in these sequence
      data. They consist of 19-30 amino acid residues encoded at the C terminus of a 73
      152 amino acid precursor and contain the motif C-x(2)-G-x(4,6)-G-x(1,2)-C-[KR],
      which shares a certain similarity with the motif in the mammalian EGF peptide
      family. These data indicate that these small cytokines belonging to one family
      are present in at least five insect orders.

PMID- 22465149
TI  - The cys-loop ligand-gated ion channel gene family of Tetranychus urticae:
      implications for acaricide toxicology and a novel mutation associated with
      abamectin resistance.
AB  - The cys-loop ligand-gated ion channel (cysLGIC) super family of Tetranychus
      urticae, the two-spotted spider mite, represents the largest arthropod cysLGIC
      super family described to date and the first characterised one within the group
      of chelicerates. Genome annotation, phylogenetic analysis and comparison of the
      cysLGIC subunits with their counterparts in insects reveals that the T. urticae
      genome encodes for a high number of glutamate- and histamine-gated chloride
      channel genes (GluCl and HisCl) compared to insects. Three orthologues of the
      insect gamma-aminobutyric acid (GABA)-gated chloride channel gene Rdl were
      detected. Other cysLGIC groups, such as the nAChR subunits, are more conserved
      and have clear insect orthologues. Members of cysLGIC family mediate endogenous
      chemical neurotransmission and they are prime targets of insecticides.
      Implications for toxicology associated with the identity and specific features of
      T. urticae family members are discussed. We further reveal the accumulation of
      known and novel mutations in different GluCl channel subunits (Tu_GluCl1 and
      Tu_GluCl3) associated with abamectin resistance in T. urticae, and provide
      genetic evidence for their causality. Our study provides useful toxicological
      insights for the exploration of the T. urticae cysLGIC subunits as putative
      molecular targets for current and future chemical control strategies.

PMID- 22465150
TI  - Prevalence and molecular detection of Anaplasma marginale, Babesia bovis and
      Babesia bigemina in cattle from Puntarenas Province, Costa Rica.
AB  - A study was conducted in 2008 to determine the prevalence of Anaplasma and
      Babesia infections in cattle in the Puntarenas Province of Costa Rica. Blood
      samples were taken from a total of 449 cattle during the month of March at 30
      farms in the region of Espiritu Santu, Costa Rica. Commercially available enzyme
      linked immunosorbent assays (ELISA) were used to determine presence of antibodies
      to Babesia bigemina and Anaplasma marginale, and real-time PCR was used to
      determine the presence of DNA from the disease-causing organisms. The ELISA
      results indicated that 87.5% of the cattle sampled were positive for antibodies
      to A. marginale, while 59.1% were positive for antibodies to B. bigemina. The
      real-time PCR results showed that 235 cattle were carrying A. marginale DNA
      (56.9%), 6 with B. bigemina DNA (1.34%), and 2 with B. bovis DNA (0.45%).

PMID- 22465151
TI  - RNA tetraplex as a primordial peptide synthesis scaffold.
AB  - Peptide bond formation at the peptidyl transferase center on the ribosome is a
      crucial phenomenon in life systems. In this study, we conceptually propose
      possible roles of the RNA tetraplex as a scaffold for two aminoacyl minihelices
      that enable peptide bond formation. The basic rationale of this model is that
      "parallel" complementary templates composed of only 10-mer nucleotides can
      position two amino acids in close proximity, which is conceptually and
      essentially similar to the situation observed in ribosomes. Using supportive
      experimental data, we discuss the origin and evolution of peptide bond formation
      in early biological systems.

PMID- 22465152
TI  - The genetic code and its optimization for kinetic energy conservation in
      polypeptide chains.
AB  - Why is the genetic code the way it is? Concepts from fields as diverse as
      molecular evolution, classical chemistry, biochemistry and metabolism have been
      used to define selection pressures most likely to be involved in the shaping of
      the genetic code. Here minimization of kinetic energy disturbances during protein
      evolution by mutation allows an optimization of the genetic code to be
      highlighted. The quadratic forms corresponding to the kinetic energy term are
      considered over the field of rational numbers. Arguments are given to support the
      introduction of notions from basic number theory within this context. The
      observations found to be consistent with this minimization are statistically
      significant. The genetic code may well have been optimized according to energetic
      criteria so as to improve folding and dynamic properties of polypeptide chains.

PMID- 22465153
TI  - New insights from structural biology into the druggability of G protein-coupled
      receptors.
AB  - The recent availability of X-ray structures for diverse ligand-bound Family A G
      protein-coupled receptors (GPCRs) in multiple conformations (inactive form with
      an antagonist/inverse agonist bound and active form with an agonist bound) now
      enables rational drug design efforts that have historically been applied to
      soluble enzyme targets. Here, we review properties of these GPCR binding sites,
      using a unique combination of calculated physicochemical properties and water
      energetics (GRID, WaterMap and SZMAP) to provide a new perspective and rational
      assessment of druggability for each GPCR target binding site. Examples are
      described from several well-studied enzyme systems to support this advanced
      structure-based approach to assessing druggability and to contrast their
      properties with those of GPCRs. Changes in receptor conformations between the
      GPCR inactive and active forms evident from the protein structures are discussed,
      yielding important pointers for rational drug design of antagonists and agonists
      and a better understanding of GPCR activation.

PMID- 22465154
TI  - Gender sensitivity in national health plans in Latin America and the European
      Union.
AB  - OBJECTIVES: To evaluate the situation regarding gender sensitivity in national
      health plans in Latin America and the European Union for the decade 2000-2010.
      METHODS: A systematic search and content analysis of national health plans were
      carried out within 37 countries. Gender sensitivity, defined as the extent to
      which a health plan considers gender as a central category and develops measures
      to reduce any gender-related inequalities, was analysed through an ad hoc
      checklist. RESULTS: The description of health problems by sex was more frequent
      than intervention proposals aimed at reducing gender health disparities. The
      greatest number of specific intervention proposals targeted at overcoming gender
      based health inequalities were associated with sexual and/or reproductive health,
      gender based violence, the working environment and human resources training.
      Compared to the European Union member states, Latin American health plans were
      found to be generally more gender sensitive. CONCLUSIONS: National health plans
      are still generally lacking in gender sensitivity. Disparities exist in health
      policy formulation in favour of men, whilst women's health continues to be
      identified mainly with reproductive health. If gender sensitivity is not taken
      into account, efforts to improve the quality of clinical care will be
      insufficient as gender inequalities will persist.

PMID- 22465155
TI  - Comparison of cardiolipins from Drosophila strains with mutations in putative
      remodeling enzymes.
AB  - Cardiolipin is a dimeric phospholipid with a characteristic acyl composition that
      is generated by fatty acid remodeling after de novo synthesis. Several enzymes
      have been proposed to participate in acyl remodeling of cardiolipin. In order to
      compare the effect of these enzymes, we determined the pattern of cardiolipin
      molecular species in Drosophila strains with specific enzyme deletions, using
      MALDI-TOF mass spectrometry with internal standards. We established the linear
      range of the method for cardiolipin quantification, determined the relative
      signal intensities of several cardiolipin standards, and demonstrated satisfying
      signal-to-noise ratios in cardiolipin spectra from a single fly. Our data
      demonstrate changes in the cardiolipin composition during the Drosophila life
      cycle. Comparison of cardiolipin spectra, using vector algebra, showed that
      inactivation of tafazzin had a large effect on the molecular composition of
      cardiolipin, inactivation of calcium-independent phospholipase A(2) had a small
      effect, whereas inactivation of acyl-CoA:lysocardiolipin-acyltransferase and of
      the trifunctional enzyme did not affect the cardiolipin composition.

PMID- 22465156
TI  - Role of the Msh2 gene in genome maintenance and development in mouse fetuses.
AB  - In an attempt to evaluate the roles of the mismatch repair gene Msh2 in genome
      maintenance and in development during the fetal stage, spontaneous mutations and
      several developmental indices were studied in Msh2-deficient lacZ-transgenic
      mouse fetuses. Mutation levels in fetuses were elevated at 9.5 dpc (days post
      coitum) when compared to wild-type mice, and the level of mutations continued to
      increase until the fetuses reached the newborn stage. The mutation levels in 4
      different tissues of newborns showed similar magnitudes to those in the whole
      body. The levels remained similar after birth until 6 months of age. The
      molecular nature of the mutations examined in 12.5 dpc fetuses of Msh2(+/+) and
      Msh2(-/-) revealed unique spectra which reflect errors produced during the DNA
      replication process, and those corrected by a mismatch repair system. Most base
      substitutions and simple deletions were reduced by the presence of the Msh2 gene,
      whereas G:C to A:T changes at CpG sequences were not affected, suggesting that
      the latter change was not influenced by mismatch repair. On the other hand,
      analysis of developmental indices revealed that there was very little effect,
      including the presence of malformations, resulting from Msh2-deficiencies. These
      results indicate that elevated mutation levels have little effect on the
      development of the fetus, even if a mutator phenotype appears at the
      organogenesis stage.

PMID- 22465157
TI  - Carotenoids and DNA damage.
AB  - Carotenoids are among the best known antioxidant phytochemicals, and are widely
      believed to contribute to the health-promoting properties of fruits and
      vegetables. Investigations of the effects of carotenoids have been carried out at
      different levels: in cultured cells, in experimental animals, and in humans.
      Studying reports from the last 5 years, we find a clear distinction between
      effects of vitamin A and pro-vitamin A carotenoids (the carotenes and beta
      cryptoxanthin), and effects of non-vitamin A carotenoids (lycopene, lutein,
      astaxanthin and zeaxanthin). Whereas the latter group are almost invariably
      reported to protect against DNA damage, whether endogenous or induced by
      exogenous agents, the provitamin A carotenoids show a more varied spectrum of
      effects, sometimes protecting and sometimes enhancing DNA damage. The tendency to
      exacerbate damage is seen mainly at high concentrations, and might be accounted
      for by pro-oxidant actions of these carotenoids.

PMID- 22465158
TI  - Novel HDL-based therapeutic agents.
AB  - Reduction in low-density lipoprotein cholesterol (LDL-C) levels has been
      associated with a 25-30% reduction in cardiovascular disease risk. However, there
      still remains a significant and quantifiable risk. Since epidemiologic data have
      demonstrated that low levels of high-density lipoprotein cholesterol (HDL-C) are
      associated with an increased risk for cardiovascular disease, novel therapeutic
      agents are currently being developed to either raise HDL-C levels or enhance HDL
      functionality. This review will highlight some of these therapeutic agents
      including cholesteryl ester transfer protein inhibitors, apolipoprotein A-I
      mimetics, RVX-208, and apolipoprotein A-I based infusion therapies. For each
      therapeutic class, an overview of the mechanism of action, pharmacokinetic data,
      and efficacy/safety evidence will be provided.

PMID- 22465159
TI  - Intranasal drug delivery: an efficient and non-invasive route for systemic
      administration: focus on opioids.
AB  - Intranasal administration is a non-invasive route for drug delivery, which is
      widely used for the local treatment of rhinitis or nasal polyposis. Since drugs
      can be absorbed into the systemic circulation through the nasal mucosa, this
      route may also be used in a range of acute or chronic conditions requiring
      considerable systemic exposure. Indeed, it offers advantages such as ease of
      administration, rapid onset of action, and avoidance of first-pass metabolism,
      which consequently offers for example an interesting alternative to intravenous,
      subcutaneous, oral transmucosal, oral or rectal administration in the management
      of pain with opioids. Given these indisputable interests, fentanyl-containing
      formulations have been recently approved and marketed for the treatment of
      breakthrough cancer pain. This review will outline the relevant aspects of the
      therapeutic interest and limits of intranasal delivery of drugs, with a special
      focus on opioids, together with an in-depth discussion of the physiological
      characteristics of the nasal cavity as well as physicochemical properties
      (lipophilicity, molecular weight, ionisation) and pharmaceutical factors
      (absorption enhancers, devices for application) that should be considered for the
      development of nasal drugs.

PMID- 22465161
TI  - Genome evolution: extinction, continuation or explosion?
AB  - Darwin recognised the processes of speciation and the frequent extinction of
      species. We now understand many of the genome-scale processes occurring during
      evolution involving mutations, amplification, loss or homogenisation of DNA
      sequences; rearrangement, fusion and fission of chromosomes; and horizontal
      transfer of genes or genomes, including processes involving hybridisation and
      polyploidy. DNA sequence information, combined with appropriate informatic tools
      and experimental approaches such as generation of synthetic hybrids, comparison
      of genotypes across environments, and modelling of genomic responses, is now
      letting us link genome behaviour with its consequences. The understanding of
      genome evolution will be of critical value both for conservation of the
      biodiversity of the plant kingdom and addressing the challenges of breeding new
      and more sustainable crops to feed the human population.

PMID- 22465160
TI  - Novel therapeutic agents for lowering low density lipoprotein cholesterol.
AB  - Elevated low density lipoprotein cholesterol (LDL-C) levels have been associated
      with an increased risk for cardiovascular disease (CVD). Despite a 25-30%
      reduction in CVD risk with LDL-C reducing strategies, there is still a
      significant residual risk. Moreover, achieving target LDL-C values in individuals
      at high CVD risk is sometimes limited because of tolerability and/or efficacy.
      Thus, novel therapeutic agents are currently being developed to lower LDL-C
      levels further. This review will highlight some of these therapeutic agents
      including anti-sense oligonucleotides focused on apolipoprotein B, proprotein
      convertase subtilisin/kexin type 9 (PCSK9) inhibitors, microsomal triglyceride
      transfer protein inhibitors, and thyromimetics. For each therapeutic class, an
      overview of the mechanism of action, pharmacokinetic data, and efficacy/safety
      evidence will be provided.

PMID- 22465162
TI  - Fungal endophytes of grasses.
AB  - Epichloae endophytes form mutualistic symbiotic associations with temperate
      grasses and confer on the host a number of bioprotective benefits through
      production of fungal secondary metabolites and changed host metabolism.
      Maintenance of this mutualistic interaction requires that growth of the endophyte
      within the host is restricted. Recent work has shown that epichloae endophytes
      grow in the leaves by intercalary division and extension rather than tip growth.
      This novel pattern of growth enables the fungus to synchronise its growth with
      that of the host. Reactive oxygen species signalling is required to maintain this
      pattern of growth. Disruption of components of the NADPH oxidase complex or a MAP
      kinase, result in a switch from restricted to proliferative growth and a
      breakdown in the symbiosis. RNAseq analysis of mutant and wild-type associations
      identifies key fungal and plant genes that define the symbiotic state. Endophyte
      genes for secondary metabolite biosynthesis are only expressed in the plant and
      under conditions of restricted growth.

PMID- 22465163
TI  - Progressive aphasia presenting with deep dyslexia and dysgraphia.
AB  - Primary progressive aphasia is clinically heterogeneous. We report a patient,
      alias Don, with a novel form of progressive aphasia, characterised by deep
      dyslexia and dysgraphia and dissociated access to phonological and orthographic
      word forms. The hallmarks of deep dyslexia and dysgraphia were present early in
      the course and persisted over time. Writing was initially poorer than reading,
      but this reversed over time. There was a lack of concordance between reading and
      writing errors. Don benefited from a semantic mediation strategy to learn letter
      sounds, involving associating letters with a country name (e.g., A=Afghanistan).
      Remarkably, he continued to be able to generate those phonologically complex
      country names when no longer able to name or sound letters. Don's performance is
      compatible with a traditional dual-route account of deep dyslexia and dysgraphia.
      The findings have potential practical implications for speech and language
      therapy in progressive aphasia. Moreover, they illustrate both the remarkable
      specificity yet clinical diversity in presentation of progressive aphasia.

PMID- 22465164
TI  - A relationship between motilin and growth hormone secretagogue receptors.
AB  - The motilin receptor (MR) belongs to a family of Class I G protein-coupled
      receptors that also includes growth hormone secretagogue receptor (GHSR). Their
      potentially unique structure and the molecular basis of their binding and
      activation are not yet clear. We previously reported that the perimembranous
      residues in the predicted extracellular loops and amino-terminal tail of the MR
      were important for responses to the natural peptide ligand, motilin, and the
      transmembrane domains of the MR were important for a non-peptidyl ligand,
      erythromycin. We also reported that the perimembranous residues in the second
      extracellular loop of the GHSR were critical for natural ligand ghrelin binding
      and activity. The MR is 52% identical to GHSR, with 86% sequence identity in the
      transmembrane domains. In the current work, to gain insight into a relationship
      between MR and GHSR, we studied functional responses to motilin, erythromycin and
      ghrelin of expression cells of chimeric constructs of MR and GHSR and co
      expression cells of both MR and GHSR. We also generated human MR transgenic mice,
      and clarified a relationship between motilin and ghrelin. MR(1-62)/GHSR(68-366)
      construct responded only to ghrelin, MR(1-102)/GHSR(108-366) responded to ghrelin
      and erythromycin, and MR(1-129)/GHSR(135-366) and MR(1-178)/GHSR(184-366)
      responded to erythromycin, while GHSR(1-183)/MR(179-412) responded to neither
      motilin, erythromycin nor ghrelin. MR and GHSR co-expression cells have no
      additional responses to these ligands. Motilin or erythromycin administration to
      human MR transgenic mice resulted in a decrease of serum acyl-ghrelin levels,
      while MR and GHSR mRNA expression in the gastrointestinal tracts were not
      changed. These data suggested that in species expressing both motilin-MR and
      ghrelin-GHSR, there is a compensatory relationship in vivo.

PMID- 22465165
TI  - Centrally acting leptin induces a resuscitating effect in haemorrhagic shock in
      rats.
AB  - Centrally acting leptin induces the activation of the sympathetic nervous system
      with a pressor effect in normotensive rats. The purpose of the study was to
      examine central leptin-evoked action in critical haemorrhagic hypotension. In
      anaesthetized male Wistar rats subjected for irreversible haemorrhagic shock with
      mean arterial pressure (MAP) 20-25 mmHg haemodynamic parameters and plasma
      concentrations of adrenaline and noradrenaline were measured. Leptin given
      intracerebroventricularly (20 MUg) evoked long-lasting rises in MAP and heart
      rate (HR), with a subsequent increase in renal, mesenteric and hindquarters blood
      flows and a 100% survival at 2 h. MAP and peripheral blood flow changes were
      inhibited by a pre-treatment with alpha(1)- and alpha(2)-adrenoceptor antagonists
      prazosin (0.5 mg/kg) and yohimbine (1 mg/kg), while beta-adrenoceptor antagonist
      propranolol (1 mg/kg) blocked leptin-induced HR changes, without influence on
      MAP, peripheral blood flows and survival. Twenty min after leptin treatment,
      there were higher plasma concentrations of noradrenaline, but not adrenaline, in
      comparison with the saline-treated control group. In conclusion, centrally acting
      leptin induces a long-lasting pressor effect with an improvement in the survival
      rate in haemorrhage-shocked rats. The effect may be associated with the
      activation of the sympathetic nervous system.

PMID- 22465167
TI  - Is unpredictable chronic mild stress (UCMS) a reliable model to study depression
      induced neuroinflammation?
AB  - Unipolar depression is one of the leading causes of disability. The
      pathophysiology of depression is poorly understood. Evidence suggests that
      inflammation is associated with depression. For instance, pro-inflammatory
      cytokines are found to be elevated in the peripheral blood of depressed subjects.
      Cytokine immunotherapy itself is known to induce depressive symptoms. While the
      epidemiological and biochemical relationship between inflammation and depression
      is strong, little is known about the possible existence of neuroinflammation in
      depression. The use of animal models of depression such as the Unpredictable
      Chronic Mild Stress (UCMS) has already contributed to the elucidation of the
      pathophysiological mechanisms of depression such as decreased neurogenesis and
      HPA axis alterations. We used this model to explore the association of depressive
      like behavior in mice with changes in peripheral pro-inflammatory cytokines IL
      1beta, TNFalpha and IL-6 level as well as the neuroinflammation by quantifying
      CD11b expression in brain areas known to be involved in the pathophysiology of
      depression. These areas include the cerebral cortex, the nucleus accumbens, the
      bed nucleus of the stria terminalis, the caudate putamen, the amygdala and the
      hippocampus. The results indicate that microglial activation is significantly
      increased in the infralimbic, cingulate and medial orbital cortices, nucleus
      accumbens, caudate putamen, amygdala and hippocampus of the mouse brain as a
      function of UCMS, while levels of pro-inflammatory cytokines did not differ among
      the groups. This finding suggests that neuroinflammation occurs in depression and
      may be implicated in the subject's behavioral response. They also suggest that
      UCMS could be a potentially reliable model to study depression-induced
      neuroinflammation.

PMID- 22465166
TI  - Combination of direct renin inhibition with angiotensin type 1 receptor blockade
      improves aldosterone but does not improve kidney injury in the transgenic Ren2
      rat.
AB  - Enhanced renin-angiotensin-aldosterone system (RAAS) activation contributes to
      proteinuria and chronic kidney disease by increasing glomerular and
      tubulointerstitial oxidative stress, promotion of fibrosis. Renin activation is
      the rate limiting step in angiotensin (Ang II) and aldosterone generation, and
      recent work suggests direct renin inhibition improves proteinuria comparable to
      that seen with Ang type 1 receptor (AT(1)R) blockade. This is important as, even
      with contemporary use of AT(1)R blockade, the burden of kidney disease remains
      high. Thereby, we sought to determine if combination of direct renin inhibition
      with AT(1)R blockade in vivo, via greater attenuation of kidney oxidative stress,
      would attenuate glomerular and proximal tubule injury to a greater extent than
      either intervention alone. We utilized the transgenic Ren2 rat with increased
      tissue RAS activity and higher serum levels of aldosterone, which manifests
      hypertension and proteinuria. Ren2 rats were treated with renin inhibition
      (aliskiren), AT(1)R blockade (valsartan), the combination (aliskiren+valsartan),
      or vehicle for 21days. Compared to Sprague-Dawley controls, Ren2 rats displayed
      increased systolic pressure (SBP), circulating aldosterone, proteinuria and
      greater urine levels of the proximal tubule protein excretory marker beta-N
      acetylglucosaminidase (beta-NAG). These functional and biochemical alterations
      were accompanied by increases in kidney tissue NADPH oxidase subunit Rac1 and 3
      nitrotyrosine (3-NT) content as well as fibronectin and collagen type III. These
      findings occurred in conjunction with reductions in the podocyte-specific protein
      podocin as well as the proximal tubule-specific megalin. Further, in transgenic
      animals there was increased tubulointerstitial fibrosis on light microscopy as
      well as ultrastructural findings of glomerular podocyte foot-process effacement
      and reduced tubular apical endosomal/lysosomal activity. Combination therapy led
      to greater reductions in SBP and serum aldosterone, but did not result in greater
      improvement in markers of glomerular and tubular injury (i.e. beta-NAG) compared
      to either intervention alone. Further, combination therapy did not improve
      markers of oxidative stress and podocyte and proximal tubule integrity in this
      transgenic model of RAAS-mediated kidney damage despite greater reductions in
      serum aldosterone and BP levels.

PMID- 22465168
TI  - The facilitating effect of clinical hypnosis on motor imagery: an fMRI study.
AB  - Hypnosis is increasingly being employed in therapy of neurologically impaired
      patients. In fact, reports from neuropsychological practice point out that
      neurological patients with a loss of motor abilities achieve successful
      rehabilitation by means of motor imagery during hypnosis. This approach was shown
      to be effective even if the patients' ability to imagine movements was impaired
      or lost. The underlying mechanisms of "how" and "where" hypnosis affects the
      brain, however, are largely unknown. To identify the brain areas involved in
      motor imagery under hypnosis, we conducted an fMRI study in which we required
      healthy human subjects either to imagine or to execute repetitive finger
      movements during a hypnotic trance. We observed fMRI-signal increases exclusively
      related to hypnosis in the left superior frontal cortex, the left anterior
      cingulate gyrus and left thalamus. While the superior frontal cortex and the
      anterior cingulate were active related more to movement performance than to
      imagery, the thalamus was activated only during motor imagery. These areas
      represent central nodes of the salience network linking primary and higher motor
      areas. Therefore, our data substantiate the notion that hypnosis enhances motor
      imagery.

PMID- 22465169
TI  - Different current intensities electrical stimulation of prelimbic cortex of mPFC
      produces different effects on morphine-induced conditioned place preference in
      rats.
AB  - The medial prefrontal cortex (mPFC) is a part of brain reward system involved in
      higher cognitive functions such as learning and memory. The mPFC receives strong
      dopaminergic innervations from ventral tegmental area (VTA) that comprises a
      portion of the mesolimbic dopaminergic system (MLDS), and in turn sends glutamate
      projection to both the VTA and nucleus accumbens (NAc). In the present study, we
      investigated the influence of electrical stimulation with different current
      intensities on prelimbic cortex (PL, subdivision of mPFC) (25, 50, 100, and 150
      MUA) with and without an effective dose of morphine (0.5 and 5 mg/kg) on CPP
      during conditioning and post-conditioning phases. Subcutaneous administration of
      morphine 5mg/kg produced significant CPP in comparison with saline group. Our
      findings also showed that electrical stimulation of PL (100 MUA) suppressed
      morphine-induced CPP that reveals impaired learning and memory formation in the
      process of conditioning through the blocking connection from the hippocampus to
      the prelimbic cortex of mPFC. A lowest current intensity (25 MUA) in combination
      with ineffective dose of morphine (0.5 mg/kg) increased morphine-induced CPP
      probability via the prove reward system.

PMID- 22465170
TI  - Odor-avoidance or odor-preference induced by amphetamine in the infant rat
      depending on the dose and testing modality.
AB  - By the second postnatal week of life infant rats can acquire taste avoidance
      induced by amphetamine. Psychostimulant drugs supports appetitive and aversive
      learning in adult rats. Their appetitive effects are more likely to become
      associated with contextual cues, while the aversive ones have been consistently
      found in taste aversion learning. To explain this paradox, it has been proposed
      that rats would avoid a taste that predicts a change in their homeostasis because
      this species cannot vomit. In this study we assessed the motivational properties
      of amphetamine in preweanling rats by means of an odor conditioning preparation,
      which enables the analysis of the hedonic value of the memory by means of a
      consumption test or in terms of locomotor approach to the odor. Results indicate
      that regardless of the amphetamine dose (1 or 5 mg/kg), when animals were
      evaluated in the intake test, subjects avoided the odor. However, the outcome in
      the locomotor avoidance test varied as a function of the amphetamine dose. Rats
      trained with the low dose (1 mg/kg) showed odor preference, while the highest
      amphetamine dose (5 mg/kg) induced odor avoidance. When LiCl was employed as an
      unconditioned stimulus (US), rats showed avoidance in the intake and locomotor
      activity tests. These data indicate that amphetamine, like other drugs of abuse,
      supports appetitive conditioning in preweanling rats. Interestingly, infant rats
      expressed conditioned odor avoidance or preference depending on the dose and
      testing modality. Results were discussed considering current theories of
      avoidance learning induced by rewarding drugs.

PMID- 22465171
TI  - Cell-penetrating peptides: classes, origin, and current landscape.
AB  - With more than ten new FDA approvals since 2001, peptides are emerging as an
      important therapeutic alternative to small molecules. However, unlike small
      molecules, peptides on the market today are limited to extracellular targets. By
      contrast, cell-penetrating peptides (CPPs) can target intracellular proteins and
      also carry other cargoes (e.g. other peptides, small molecules or proteins) into
      the cell, thus offering great potential as future therapeutics. In this review I
      present a classification scheme for CPPs based on their physical-chemical
      properties and origin, and I provide a general framework for understanding and
      discovering new CPPs.

PMID- 22465172
TI  - Fire in the ashes: can failed Alzheimer's disease drugs succeed with second
      chances?
AB  - BACKGROUND: Since Cognex, more than 200 Alzheimer's disease (AD) drug candidates
      have failed. Investigations have identified vulnerabilities of these AD drug
      developments to methodological errors. (-)-Phenserine has been discussed as
      possibly failing due to flawed methods and practices in development. METHODS: We
      analyzed documentation of (-)-phenserine's development for vulnerabilities to
      errors and designed interventions for a redevelopment that could provide fair or
      unbiased assessments of (-)-phenserine target engagement, target relevance for
      human diseases, and adequate presumptive evidence of efficacy as a therapeutic
      for one or more diagnoses to justify registration-required clinical trials.
      RESULTS: Similar to studies of 40 other AD developments, with (-)-phenserine, we
      found little evidence of preemptive interventions against potentially
      invalidating errors, grounds to judge progress in development through stages as
      not scientifically justifiable, and variance excess and placebo group
      improvements as capable of accounting for outcomes from various studies in the
      development. We propose to compare a redevelopment resourced to counter these
      deficiencies with the original development as historical control to evaluate
      further our hypothesis that errors in development accounted for the (-)
      phenserine failure, specifically, and other AD drug failures, potentially.
      CONCLUSIONS: We find support for our earlier proposal that (-)-phenserine did not
      fail, but the methods of development did fail, to provide conditions where
      efficacy could be tested. We propose that redevelopment under conditions aimed to
      correct methodological deficiencies common in AD drug developments will
      successfully test efficacy for (-)-phenserine and hopefully lead to a disease
      modifying addition to the AD therapeutic armamentarium.

PMID- 22465173
TI  - Gaining precision on the Alzheimer's Disease Assessment Scale-cognitive: a
      comparison of item response theory-based scores and total scores.
AB  - BACKGROUND: The Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) is a
      commonly used measure for assessing cognitive dysfunction in patients with
      Alzheimer's disease (AD). The measure has 11 subscales, each of which captures an
      important aspect of cognitive dysfunction in AD. Traditional scoring of the ADAS
      cog involves adding up the scores from the subscales without regarding their
      varying difficulty or their strength of relationship to AD-associated cognitive
      dysfunction. The present article analyzes problems associated with this approach
      and offers solutions for gaining measurement precision by modeling how the
      subscales function. METHODS: We analyzed data collected at the Baylor College of
      Medicine Alzheimer's Disease and Memory Disorders Clinic from 1240 patients
      diagnosed with varying degrees of dementia. Item response theory was used to
      determine the relationship between total scores on the ADAS-cog and the
      underlying level of cognitive dysfunction reflected by the scores. RESULTS:
      Results revealed that each total score corresponded to a spectrum of cognitive
      dysfunction, indicating that total scores were relatively imprecise indicators of
      underlying cognitive dysfunction. Furthermore, it was common for two individuals
      with the same total score to have significantly different degrees of cognitive
      dysfunction. CONCLUSIONS: These findings suggest that item response theory
      scoring of the ADAS-cog may measure cognitive dysfunction more precisely than a
      total score method.

PMID- 22465174
TI  - Alzheimer's disease: pathogenesis and prevention.
AB  - Tau lesions (pretangles, neuropil threads, neurofibrillary tangles) in select
      neuronal types are essential to the pathogenesis of Alzheimer's disease.
      Pretangle formation marks the beginning of the pathological process and is of
      particular interest because it is temporally closer to the prevailing conditions
      that induce the pathological process underlying Alzheimer's disease in contrast
      to late-stage disease. However, not all pretangles convert into neurofibrillary
      tangles. We propose that the development of tau lesions in Alzheimer's disease is
      traceable to differences between early- versus late-maturing oligodendrocytes and
      to the exceptionally protracted myelination of late-developing portions of the
      human brain. Conclusions drawn from these considerations should encourage
      development of new preventative and disease-modifying strategies.

PMID- 22465176
TI  - Medical and environmental risk factors associated with frontotemporal dementia: a
      case-control study in a veteran population.
AB  - BACKGROUND: Compared with other major dementias, very little is known about the
      medical and environmental risk factors associated with frontotemporal dementia
      (FTD). In this study, we evaluated medical and environmental disorders associated
      with FTD in a veteran population. METHODS: The medical records of 845 consecutive
      veterans who were evaluated for cognitive and/or behavioral complaints at a
      cognitive disorders clinic in an academic medical center between March 1, 2003,
      and June 30, 2008, were reviewed and 554 patients received a diagnosis of
      dementia. Medical disorders and environmental risk factors in 63 patients with
      behavioral variant of FTD were compared with 491 patients with non-FTD dementias.
      RESULTS: The prevalence of traumatic brain injury (TBI) was significantly greater
      in patients with FTD versus those with non-FTD dementias (12.7% vs 3.5%; P <
      .05). The FTD group also had a lower prevalence of heart disease (19.0% vs 36.7%;
      P < .05) and cerebrovascular diseases (12.7% vs 26.1%; P < .05), although the
      prevalence of vascular risk factors was comparable between FTD and non-FTD
      dementia groups: hypertension (65.1% vs 68.2%), diabetes (31.7% vs 26.9%),
      hyperlipidemia (42.9% vs 48.9%), and tobacco use (7.9% vs 8.8%; P > .05 for all).
      In multivariate analysis, the risk for FTD was increased in patients with TBI
      (OR, 4.4; 95% CI, 1.6-11.8). The risk for FTD was marginally decreased in
      patients with heart disease (OR, 0.4; 95% CI, 0.3-0.96). CONCLUSIONS: In a
      clinical sample of veterans, risk of FTD was increased in patients with TBI and
      marginally decreased in patients with heart disease. Prospective studies are
      needed to confirm these associations temporally and to identify their underlying
      mechanisms.

PMID- 22465175
TI  - Diuretic use is associated with better learning and memory in older adults in the
      Ginkgo Evaluation of Memory Study.
AB  - BACKGROUND: To investigate the association between diuretics, angiotensin
      converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (AT2RB),
      and cognitive function. METHODS: This post hoc analysis of the randomized
      controlled Ginkgo Evaluation of Memory Study trial focuses on 3069 nondemented
      community-dwelling participants aged >75 years. At baseline visit, detailed
      information about medication use was collected and five cognitive domains were
      assessed. Multivariate linear regression analyses were used to assess cross
      sectional associations between medication use and cognitive function. RESULTS: In
      all, 36% of participants reported history of hypertension and 53% reported
      antihypertensive medication use, with 17% reporting diuretic, 11% ACE-I, and 2%
      AT2RB use. Potassium-sparing diuretic use (N = 192) was associated with better
      verbal learning and memory measured by California Verbal Learning Test as
      compared with no antihypertensive medication users (beta = 0.068, P = .01; beta =
      0.094, P < .001) and other antihypertensive medication users (beta = 0.080, P =
      .03; beta = 0.153, P < .001). Use of ACE-I or AT2RB was not associated with
      better cognitive function. CONCLUSION: Results warrant further investigation into
      possible protective effects of potassium-sparing diuretics and the role of
      potassium in mitigating cognitive decline.

PMID- 22465177
TI  - Novel role of Zn(II)-curcumin in enhancing cell proliferation and adjusting
      proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute
      gastric ulcers.
AB  - Alcohol consumption can induce gastric ulcers and zinc deficiency. Zinc complexes
      were reported to have anti-ulcer activity as it acts as an anti-inflammatory and
      antioxidant. Zn(II)-curcumin complex and its solid dispersions (SDs) were
      synthesized and evaluated for its gastroprotective activity and mechanism against
      ethanol-induced ulcer. The Swiss murine fibroblast cell line (3T3) was used as an
      alternative in vitro model to evaluate the effects of Zn(II)-curcumin on cell
      proliferation. Zn(II)-curcumin were administered orally for seven consecutive
      days prior to induction of ulcers using ethanol. Gross and microscopic lesions,
      immunological and biochemical parameters were taken into consideration. The
      results showed that solid dispersions (SDs) of Zn(II)-curcumin (2.5-20 MUM)
      enhanced the proliferation of 3T3 cells more significantly than curcumin at the
      same concentrations (P<0.01). Oral administration of Zn(II)-curcumin (12, 24 and
      48 mg/kg) SDs dose-dependently prevented formation of ulcer lesions induced by
      ethanol. The levels of proinflammatory cytokines tumor necrosis factor-alpha (TNF
      alpha), interleukin 6 (IL-6), and oxidative stress superoxide dismutase (SOD),
      glutathione peroxidase (GPX-Px), malonaldehyde (MDA) and H(+)-K(+)-ATPase were in
      the rats exposed to ethanol in ulceration have been altered. Zn(II)-curcumin
      prevented formation of ulcer lesions, significantly inhibited TNF-alpha and IL-6
      mRNA expression, increased the activity of SOD and GSH-Px, reduced MDA levels and
      H(+)-K(+)-ATPase in mucosa of rats compared to controls (P<0.05). These findings
      suggest that the gastroprotective activity of Zn(II)-curcumin complex might
      contribute in stimulating cell proliferation and adjusting the proinflammatory
      cytokine-mediated oxidative damage to the gastric mucosa.

PMID- 22465178
TI  - Combined astaxanthin and fish oil supplementation improves glutathione-based
      redox balance in rat plasma and neutrophils.
AB  - The present study aimed to investigate the effects of daily (45 days) intake of
      fish oil (FO; 10mg EPA/kg body weight (BW) and 7 mg DHA/kg BW) and/or natural
      ASTA (1mg ASTA/kg BW) on oxidative stress and functional indexes of neutrophils
      isolated from Wistar rats by monitoring superoxide (O(2)(-)), hydrogen peroxide
      (H(2)O(2)), and nitric oxide (NO()) production compared to the progression of
      auto-induced lipid peroxidation and Ca(2+) release in activated neutrophils.
      Furthermore, phagocytic capacity, antioxidant enzyme activities, glutathione
      recycling system, and biomarkers of lipid and protein oxidation in neutrophils
      were compared to the redox status. Our results show evidence of the beneficial
      effects of FO+ASTA supplementation for immune competence based on the redox
      balance in plasma (significant increase in GSH-dependent reducing power), non
      activated neutrophils (increased activity of the glutathione-recycling enzymes
      GPx and GR) and PMA-activated neutrophils (lower O(2)(-), H(2)O(2), and NO()
      generation, reduced membrane oxidation, but higher phagocytic activity). Combined
      application of ASTA and FO promoted hypolipidemic/hypocholesterolemic effects in
      plasma and resulted in increased phagocytic activity of activated neutrophils
      when compared with ASTA or FO applied alone. In PMA-activated neutrophils, ASTA
      was superior to FO in exerting antioxidant effects. The bulk of data reinforces
      the hypothesis that habitual consumption of marine fish (e.g. salmon, which is a
      natural source of both astaxanthin and fish oil) is beneficial to human health,
      in particular by improving immune response and lowering the risk of vascular and
      infectious diseases.

PMID- 22465179
TI  - Honokiol induces cell cycle arrest and apoptosis via inhibition of survival
      signals in adult T-cell leukemia.
AB  - BACKGROUND: Honokiol, a naturally occurring biphenyl, possesses anti-neoplastic
      properties. We investigated activities of honokiol against adult T-cell leukemia
      (ATL) associated with human T-cell leukemia virus type 1 (HTLV-1). METHODS: Cell
      viability was assessed using colorimetric assay. Propidium iodide staining was
      performed to determine cell cycle phase. Apoptotic effects were evaluated by 7A6
      detection and caspases activity. Expressions of cell cycle- and apoptosis
      associated proteins were analyzed by Western blot. We investigated the efficacy
      of honokiol in mice harboring tumors of HTLV-1-infected T-cell origin. RESULTS:
      Honokiol exhibited cytotoxic activity against HTLV-1-infected T-cell lines and
      ATL cells. We identified two different effects of honokiol on HTLV-1-infected T
      cell lines: cell cycle inhibition and induction of apoptosis. Honokiol induced G1
      cell cycle arrest by reducing the expression of cyclins D1, D2, E, CDK2, CDK4,
      CDK6 and c-Myc, while apoptosis was induced via reduced expression of cIAP-2,
      XIAP and survivin. The induced apoptosis was also associated with activation of
      caspases-3 and -9. In addition, honokiol suppressed the phosphorylation of
      IkappaBalpha, IKKalpha, IKKbeta, STAT3, STAT5 and Akt, down-regulated JunB and
      JunD, and inhibited DNA binding of NF-kappaB, AP-1, STAT3 and STAT5. These
      effects resulted in the inactivation of survival signals including NF-kappaB, AP
      1, STATs and Akt. Honokiol was highly effective against ATL in mice CONCLUSIONS:
      Our data suggested that honokiol is a systemically available, non-toxic inhibitor
      of ATL cell growth that should be examined for potential clinical application.
      GENERAL SIGNIFICANCE: Our findings provide a rationale for clinical evaluation of
      honokiol for the management of ATL.

PMID- 22465180
TI  - Natural and synthetic retinoids afford therapeutic effects on intracerebral
      hemorrhage in mice.
AB  - We have recently proposed that retinoic acid receptor (NR1B) is a promising
      target of neuroprotective therapy for intracerebral hemorrhage, since
      pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various
      pathological and neurological abnormalities associated with the disease. In the
      present study we further addressed the effects of retinoids as potential
      therapeutic drugs, using a collagenase-induced model of intracerebral hemorrhage.
      Daily oral administration of all-trans retinoic acid (ATRA; 5 and 15 mg/kg), a
      naturally occurring NR1B agonist, from 1 day before collagenase injection
      significantly inhibited loss of neurons within the hematoma. ATRA in the same
      treatment regimen also decreased the number of activated microglia/macrophages
      around the hematoma but did not affect the hematoma volume. ATRA (15 mg/kg) as
      well as Am80 (5mg/kg) rescued neurons in the central region of hematoma, even
      when drug administration was started from 6h after induction of intracerebral
      hemorrhage. However, in this post-treatment regimen, only Am80 significantly
      decreased the number of activated microglia/macrophages. With regard to
      neurological deficits, both ATRA (15 mg/kg) and Am80 (5mg/kg) given in the post
      treatment regimen improved performance of mice in the beam-walking test and the
      modified limb-placing test. ATRA and Am80 also significantly attenuated damage of
      axon tracts as revealed by amyloid precursor protein immunohistochemistry. These
      results underscore potential therapeutic values of NR1B agonists for
      intracerebral hemorrhage.

PMID- 22465181
TI  - Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A
      on human epithelial ovarian carcinoma cells via activation of death receptor and
      mitochondrial pathways.
AB  - Natural phenol licorice compounds have been shown to induce apoptosis in cancer
      cells. 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) may enhance the
      sensitivity of cancer cells to anticancer drugs. However, the combined effect of
      licochalcone A and YC-1 on cell death in ovarian cancer cells has not been
      studied. We assessed the combined effect of licochalcone A and YC-1 on apoptosis
      in human epithelial ovarian carcinoma cell lines in relation to the cell death
      process. In the OVCAR-3 and SK-OV-3 cell lines, licochalocone A induced a
      decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels; an increase in Bax
      levels; loss of the mitochondrial transmembrane potential; cytochrome c release;
      activation of caspases (-8, -9 and -3); cleavage of PARP-1; and an increase in
      the tumor suppressor p53 levels. YC-1 enhanced licochalcone A-induced apoptosis
      related protein activation, nuclear damage and cell death. These results suggest
      that YC-1 may potentiate the apoptotic effect of licochalcone A on ovarian
      carcinoma cell lines by increasing the activation of the caspase-8- and Bid
      dependent pathway and the mitochondria-mediated apoptotic pathway, leading to
      caspase activation. The combination of licochalcone A and YC-1 may confer a
      benefit in the treatment of human epithelial ovarian adenocarcinoma.

PMID- 22465182
TI  - Enhanced vasorelaxant effects of the endocannabinoid-like mediator, oleamide, in
      hypertension.
AB  - Oleamide is an endocannabinoid-like, fatty acid amide with structural
      similarities to anandamide. The cardiovascular effects of anandamide are enhanced
      in hypertension and we have now examined how hypertension affects responses to
      oleamide. Vasorelaxant responses to oleamide were significantly (P<0.001)
      enhanced in aortic rings from spontaneously hypertensive rats (SHRs), such that
      the maximal relaxation to oleamide was 40.3 +/- 3.5%, compared to 15.7 +/- 3.9%
      in normotensive Wistar Kyoto (WKY) controls. The augmented responses to oleamide
      in SHR arteries were unaffected by either inhibition of nitric oxide synthase
      (300 MUM l-NAME) or fatty acid amide hydrolase (1 MUM URB597) and independent of
      cannabinoid CB(1) receptors or the endothelium. The enhanced responses to
      oleamide were opposed by pre-treatment with capsaicin (such that R(max) was
      reduced to 9.8 +/- 1.5%) and this occurred independently of TRPV1 receptor and
      sensory nerve activity, as the TRPV1 antagonist capsazepine (1-5 MUM) and the
      cation channel inhibitor ruthenium red (10 MUM) had no effect on the responses to
      oleamide. However, inhibition of cyclooxygenase (10 MUM indomethacin) enhanced
      the responses in the WKY aortae, such that the responses were comparable to those
      in the SHR. The results suggest that the cyclooxygenase pathway has a role in
      modulating vasorelaxation caused by oleamide in normotensive aortae and that this
      is lost in hypertension, possibly as an adaptation to the increase in blood
      pressure.

PMID- 22465183
TI  - Characterization of alpha(2B)-adrenoceptor ligand binding in the presence of
      muscarinic toxin alpha and delineation of structural features of receptor binding
      selectivity.
AB  - Muscarinic toxin alpha (MTalpha), a peptide isolated from the venom of the
      African black mamba, was recently found to selectively antagonize the human
      alpha(2B)-adrenoceptor. To gain more information about the binding of this
      peptide toxin, we studied the properties of the [3H]UK14,304 agonist and the
      [3H]MK-912 antagonist binding to the alpha(2B)-adrenoceptor in the presence of
      MTalpha. In equilibrium binding experiments, MTalpha decreased the binding of the
      orthosteric ligands, but failed to completely displace these. This effect of
      MTalpha was due to noncompetitive inhibition of B(max) without change in
      radioligand affinity. On the contrary, cellular signaling via the alpha(2B)
      adrenoceptor could be titrated to zero despite the incomplete receptor blockade.
      To locate binding sites for MTalpha on the receptor protein, we generated
      chimeric receptors of alpha(2B)- and alpha(2A)- or alpha(2C)-adrenoceptors. Data
      based on these constructs revealed the extracellular loop two (ECL2) as the
      structural entity that enables MTalpha binding. Cumulative exchange of parts of
      ECL2 of alpha(2B) for alpha(2A)-adrenoceptor sequence resulted in a gradual
      decrease in the affinity for MTalpha, indicating that MTalpha binds to the
      alpha(2B)-adrenoceptor through multiple sites dispersed over the whole ECL2.
      Together the results suggest that binding of MTalpha to the alpha(2B)
      adrenoceptor occludes orthosteric ligand access to the binding pocket. Putative
      homomeric receptor complexes as factors underlying the apparent noncompetitivity
      are also discussed.

PMID- 22465184
TI  - Cardiovascular baroreceptor activity and selective inhibition of monoamine
      oxidase.
AB  - Cardiovascular baroreceptor responsiveness of conscious rats treated with
      selective inhibitors of monoamine oxidase (MAO) types A and B was determined by
      measurement of blood pressure (BP) and heart rate (HR) responses to intravenous
      injection of phenylephrine and sodium nitroprusside. Treatment with selegiline (1
      or 5 mg/kg p.o. daily for 7 days) did not significantly modify resting levels of
      BP and HR, lower or upper HR plateau levels, or HR/BP gain. Treatment with
      clorgyline (2 mg/kg p.o. daily for 7 days) increased HR/BP gain but also did not
      modify resting BP or HR, or lower and upper plateau levels of HR. The results are
      compatible with an effect of MAO-A inhibition to modify monoamine levels in
      medullary areas participating in CNS control of blood pressure.

PMID- 22465185
TI  - The sigma-1 receptor antagonist PB212 reduces the Ca2+-release through the
      inositol (1, 4, 5)-trisphosphate receptor in SK-N-SH cells.
AB  - Sigma-1 receptors are specifically located at the endoplasmic reticulum
      mitochondrion interface, but upon stimulation by ligands or under prolonged
      cellular stress, they translocate to other areas of the cell. Sigma-1 receptors
      are involved in the regulation of intracellular [Ca(2+)] by affecting the Ca(2+)
      influx or the release from intracellular stores. In SK-N-SH cells, we measured
      the affinity of 4-methyl-1-[4-(6-methoxynaphthalen-1-yl)butyl]piperidine (PB212)
      at sigma-1 receptor by using a competition binding assay with specific
      radioligand; we obtained a K(i) value=316 +/- 19 nM. PB212 also showed an
      antiproliferative effect in SK-N-SH cells (EC(50)=32 +/- 4 MUM) but had no effect
      in MCF7 cells, which only express sigma-2 receptor; these findings suggest that
      PB212 behaves as a sigma-1 receptor antagonist. We have studied the effect of
      PB212 on Ca(2+) homeostasis of the SK-N-SH cell line with the fluorescent probe
      Fura-2. 100 MUM PB212 induced a Ca(2+)-efflux from the endoplasmic reticulum
      through the inositol (1, 4, 5)-trisphosphate (IP(3)) receptor. Moreover, [PB212]
      ranging from 1 to 100MUM reduced the Ca(2+)-response, triggered by carbachol or
      bradykinin that engage the phospholipase C/IP(3) pathway; such a response is
      generally increased by sigma-1 receptor agonists. On the other hand, PB212 did
      not reduce the Ca(2+)-response mediated by IP(3) in LoVo cells, which do not
      express neither sigma-1 nor sigma-2 receptors, and in MCF7 cells. The fact that
      the activity of the sigma-1 receptor can be experimentally modulated by agonists
      and antagonists supports the intriguing hypothesis that some endogenous
      molecules, unknown at the moment, modulate the sigma-1 receptor and its cellular
      targets.

PMID- 22465186
TI  - Overlapping binding of PhoP and AfsR to the promoter region of glnR in
      Streptomyces coelicolor.
AB  - Growth of soil bacteria is often limited by the availability of essential
      nutrients such as carbon, nitrogen and phosphate. The reaction to a specific
      nutrient starvation triggers interconnected responses to equilibrate the
      metabolism. It is known that PhoP (response regulator involved in phosphate
      control) specifically binds to several promoters of genes involved in nitrogen
      metabolism which are also regulated by GlnR (regulator involved in nitrogen
      control). In this article we report a novel cross-talk between GlnR and the SARP
      like regulator, AfsR. AfsR binds to some PhoP-regulated promoters including those
      of afsS (a small regulatory protein of secondary metabolism), pstS (a component
      of the phosphate transport system) and phoRP (encoding the two component system
      itself). We have characterized the regulation exerted upon the nitrogen regulator
      glnR gene by AfsR, using EMSA and DNase I footprinting assays as well as in vivo
      expression studies with DeltaphoP, DeltaafsR and DeltaafsR-DeltaphoP mutants.
      Both PhoP and AfsR proteins are able to bind to overlapping regions within the
      glnR promoter producing different effects. This work demonstrates a cross-talk of
      three different regulators of both primary and secondary metabolism.

PMID- 22465187
TI  - Striatal NMDA receptors gate cortico-pallidal synchronization in a rat model of
      Parkinson's disease.
AB  - Anomalous patterns of synchronization between basal ganglia and cortex underlie
      the symptoms of Parkinson's disease. Computational modeling studies suggest that
      changes in cortical feedback loops involving trans-striatal and trans-subthalamic
      circuits bring up this anomalous synchronization. We asked whether striatal
      outflow synchronizes globus pallidus neurons with cortical activity in a rat
      model of Parkinson's disease. We found that striatal firing is highly increased
      in rats with chronic nigrostriatal lesion and that this hyperactivity can be
      reduced by locally infusing a competitive NMDA receptor antagonist. Moreover,
      NMDA receptor-dependent striatal output had frequency dependent effects on
      distinct pathological patterns of cortico-pallidal coupling. Blockade of striatal
      NMDA receptors almost completely abolished an anomalous ~1Hz cortico-pallidal
      anti-phase synchronization induced by nigrostriatal degeneration. Moreover, under
      striatal NMDA receptor blockade, synchronization with 2.5-5Hz cortical
      oscillations falls to negligible levels and oscillations at 10-20Hz are markedly
      attenuated, whereas beta synchronization (with a peak at ~26Hz) is marginally
      reduced. Thus, tonic activation of striatal NMDA receptors allows different forms
      of anomalous oscillations along the cortico-striato-pallidal axis. Moreover, the
      frequency dependent effects of NMDA receptors suggest that low and high frequency
      parkinsonian oscillations stem from partially different mechanisms. Finally, our
      results may help to reconcile views about the contributions of changes in firing
      rate and oscillatory synchronization to Parkinson's disease symptoms by showing
      that they are related to each other.

PMID- 22465188
TI  - Undifferentiated carcinoma in oncocytic Schneiderian papilloma. A rarity.

PMID- 22465189
TI  - Negative pressure pulmonary oedema after septoplasty.
AB  - Negative pressure pulmonary oedema (NPPO) is an anaesthetic complication due to
      acute obstruction of the upper airway, whose main cause is laryngospasm. The
      pathophysiology involves a strong negative intrapleural pressure during
      inspiration against a closed glottis, which triggers excessive pressure in the
      pulmonary microvasculature. Although its diagnosis can be difficult, its
      recognition helps to minimise morbidity and mortality. This article presents a
      case of NPPO due to postextubation laryngospasm. 

PMID- 22465190
TI  - Extensive laryngopharyngeal cavernous lymphangioma causing upper airway
      obstruction.

PMID- 22465191
TI  - Label-free quantitative proteomics reveals differentially regulated proteins in
      the latex of sticky diseased Carica papaya L. plants.
AB  - Papaya meleira virus (PMeV) is so far the only described laticifer-infecting
      virus, the causal agent of papaya (Carica papaya L.) sticky disease. The effects
      of PMeV on the laticifers' regulatory network were addressed here through the
      proteomic analysis of papaya latex. Using both 1-DE- and 1D-LC-ESI-MS/MS, 160
      unique papaya latex proteins were identified, representing 122 new proteins in
      the latex of this plant. Quantitative analysis by normalized spectral counting
      revealed 10 down-regulated proteins in the latex of diseased plants, 9 cysteine
      proteases (chymopapain) and 1 latex serine proteinase inhibitor. A repression of
      papaya latex proteolytic activity during PMeV infection was hypothesized. This
      was further confirmed by enzymatic assays that showed a reduction of cysteine
      protease-associated proteolytic activity in the diseased papaya latex. These
      findings are discussed in the context of plant responses against pathogens and
      may greatly contribute to understand the roles of laticifers in plant stress
      responses.

PMID- 22465192
TI  - Temporal/spatial resolution improvement of in vivo DCE-MRI with compressed
      sensing-optimized FLASH.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides critical
      information regarding tumor perfusion and permeability by injecting a T(1)
      contrast agent, such as Gd-DTPA, and making a time-resolved measurement of signal
      increase. Both temporal and spatial resolutions are required to be high to
      achieve an accurate and reproducible estimation of tumor perfusion. However, the
      dynamic nature of the DCE experiment limits simultaneous improvement of temporal
      and spatial resolution by conventional methods. Compressed sensing (CS) has
      become an important tool for the acceleration of imaging times in MRI, which is
      achieved by enabling the reconstruction of subsampled data. Similarly, CS
      algorithms can be utilized to improve the temporal/spatial resolution of DCE-MRI,
      and several works describing retrospective simulations have demonstrated the
      feasibility of such improvements. In this study, the fast low angle shot sequence
      was modified to implement a Cartesian, CS-optimized, sub-Nyquist phase encoding
      acquisition/reconstruction with multiple two-dimensional slice selections and was
      tested on water phantoms and animal tumor models. The mean voxel-level
      concordance correlation coefficient for Ak(ep) values obtained from *4 and *8
      accelerated and the fully sampled data was 0.87+/-0.11 and 0.83+/-0.11,
      respectively (n=6), with optimized CS parameters. In this case, the reduction of
      phase encoding steps made possible by CS reconstruction improved effectively the
      temporal/spatial resolution of DCE-MRI data using an in vivo animal tumor model
      (n=6) and may be useful for the investigation of accelerated acquisitions in
      preclinical and clinical DCE-MRI trials.

PMID- 22465193
TI  - Mosquito/microbiota interactions: from complex relationships to biotechnological
      perspectives.
AB  - To date around 3500 different species of mosquito have been described, several
      tens of which are vectors of pathogens of remarkable interest in public health.
      Mosquitoes are present all around the world showing a great ability to adapt to
      very different types of habitats where they play relevant ecological roles. It is
      very likely that components of the mosquito microbiota have given the mosquito a
      great capacity to adapt to different environments. Current advances in
      understanding the mosquito-microbiota relationships may have a great impact in a
      better understanding of some traits of mosquito biology and in the development of
      innovative mosquito-borne disease-control strategies aimed to reduce mosquito
      vectorial capacity and/or inhibiting pathogen transmission.

PMID- 22465194
TI  - The role of classical and non-classical HLA class I antigens in human tumors.
AB  - In human tumors alterations in the surface expression and/or function of the
      major histocompatibility complex (MHC) class I antigens are frequently found and
      equip neoplastic cells with mechanisms to escape immune control. The aberrant
      expression of HLA class I molecules can be caused by structural alterations or
      dysregulations of genes encoding the classical HLA class I antigens and/or
      components of the HLA class I antigen processing machinery (APM). The
      dysregulation of APM components could occur at the epigenetic, transcriptional or
      post-transcriptional level. In some malignancies these abnormalities are
      significantly associated with a higher tumor staging, grading, disease
      progression and a reduced survival of patients as well as a failure to CD8(+) T
      cell-based immunotherapies. In addition to HLA class I abnormalities, expression
      of the non-classical HLA-G antigen is often induced in tumors, which could be
      mediated by various microenvironmental factors. Interestingly, soluble HLA-G
      serum and plasma levels have been useful markers for the prediction of some
      malignancies. The biological consequence of HLA-G expression or sHLA-G is an
      escape from T and NK cell-mediated recognition. Thus, alterations of non
      classical and classical HLA class I antigens and components of the antigen
      processing pathway provide tumor cells with different mechanisms to inactivate
      immune responses resulting in tumor growth and evasion from host immune
      surveillance.

PMID- 22465195
TI  - Taxane resistance in breast cancer: mechanisms, predictive biomarkers and
      circumvention strategies.
AB  - BACKGROUND: Taxanes are established in the treatment of metastatic breast cancer
      (MBC) and early breast cancer (EBC) as potent chemotherapy agents. However, their
      therapeutic usefulness is limited by de-novo refractoriness or acquired
      resistance, which are common drawbacks to most anti-cancer cytotoxics.
      Considering that the taxanes will remain principle chemotherapeutic agents for
      the treatment of breast cancer, we reviewed known mechanisms of resistance in
      with an outlook of optimizing their clinical use. METHODS: We searched the PubMed
      and MEDLINE databases for articles (from inception through to 9th January 2012;
      last search 10/01/2012) and journals known to publish information relevant to
      taxane chemotherapy. We imposed no language restrictions. Search terms included:
      cancer, breast cancer, response, resistance, taxane, paclitaxel, docetaxel,
      taxol. Due to the possibility of alternative mechanisms of resistance all
      combination chemotherapy treated data sets were removed from our overview.
      RESULTS: Over-expression of the MDR-1 gene product Pgp was extensively studied in
      vitro in association with taxane resistance, but data are conflicting. Similarly,
      the target components microtubules, which are thought to mediate refractoriness
      through alterations of the expression pattern of tubulins or microtubule
      associated proteins and the expression of alternative tubulin isoforms, failed to
      confirm such associations. Little consensus has been generated for reported
      associations between taxane-sensitivity and mutated p53, or taxane-resistance and
      overexpression of Bcl-2, Bcl-xL or NFkB. In contrary sufficient in vitro data
      support an association of spindle assembly checkpoint (SAC) defects with
      resistance. Clinical data have been limited and inconsistent, which relate to the
      variety of methods used, lack of standardization of cut-offs for quantitation,
      differences in clinical endpoints measured and in methods of tissue collection
      preparation and storage, and study/patient heterogeneity. The most prominent
      finding is that pharmaceutical down-regulation of HER-2 appears to reverse the
      taxane resistance. CONCLUSIONS: Currently no valid practical biomarkers exist
      that can predict resistance to the taxanes in breast cancer supporting the
      principle of individualized cancer therapy. The incorporation of several
      biomarker analyses into prospectively designed studies in this setting are
      needed.

PMID- 22465196
TI  - Colorectal cancer chemoprevention by trans-resveratrol.
AB  - trans-Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural phytoalexin
      present in grapes, red wine, berries and peanuts with health protecting
      properties. The low oral bioavailability indicated for this polyphenol, with the
      intestine as a bottleneck to its absorption, has promoted the large intestine as
      a potential target site for its chemopreventive activity. This review
      recapitulates the current evidence of the effects of trans-resveratrol on colon
      cancer. First, we describe the studies conducted in vitro which show that the
      protective activity takes place by inhibition of proliferation and induction of
      apoptosis. Secondly, the chemopreventive activity in animal models of colon
      carcinogenesis is revised. trans-Resveratrol not only reduces the number of
      preneoplastic lesions but also the incidence and multiplicity of tumors. Lastly,
      the article also reviews the available data on clinical trials. Altogether, the
      present findings support the hypothesis that the oral administration of trans
      resveratrol might contribute to the prevention of colon carcinogenesis.

PMID- 22465197
TI  - On-line two dimensional liquid chromatography/mass spectrometry for the analysis
      of triacylglycerides in peanut oil and mouse tissue.
AB  - Triacylglycerides (TAGs) are a large class of complex neutral lipids that
      naturally occur in both plants and animals. In the present work, an on-line
      comprehensive silver-ion liquid chromatography (silver-ion LC) * reversed-phase
      liquid chromatography (RPLC) system was constructed to analyze these compounds. A
      micro bore silver-ion modified column was employed in the first dimension with
      the commonly used hexane-based mobile phase. After a series of C18 columns were
      assessed, a wide bore column packed with 1.5 MUm particles was selected as the
      second dimension column to reduce the negative effect caused by the large volume
      and strong solvent injection in the second dimension. The system coupled with
      mass spectrometry was applied to the analysis of an edible peanut oil and a mouse
      liver extract. Twenty-eight TAGs from the peanut oil and forty-four from the
      mouse liver were identified based on the TAGs' retention behaviors on the
      comprehensive two-dimensional LC system and their APCI MS fragments.

PMID- 22465198
TI  - Analysis of Panax notoginseng metabolites in rat bile by liquid chromatography
      quadrupole time-of-flight mass spectrometry with microdialysis sampling.
AB  - A dynamic microdialysis sampling method with liquid chromatography-quadrupole
      time-of-flight mass spectrometry (Q-TOF-MS) was developed for rapid and sensitive
      analysis of the metabolite profile of Panax notoginseng extract (PNE) in rat
      bile. In vivo studies in male Sprague-Dawley rats were performed with
      microdialysis probes implanted into the bile duct before bile samples were
      collected from 0 to 12h. Metabolites of PNE were identified using dynamic
      adjustment of the fragmentor voltage to produce structure-relevant fragment ions.
      The mass accuracy of precursor and fragment ions was typically within 5 ppm of
      the theoretical values. We identified 7 compounds: 4 parent compounds
      (notoginsenoside R1, ginsenosides Rg1, Rb1, and Rd) and 3 metabolites
      (ginsenosides Rg2, Rh2, and compound K). Data from this study suggest that this
      microdialysis technique could be used in notoginseng saponin metabolic animal
      studies.

PMID- 22465199
TI  - Liquid chromatography-electrospray quadrupole linear ion trap mass spectrometry
      method for the quantitation of palonosetron in human plasma and urine:
      Application to a pharmacokinetic study.
AB  - The new analytical method for the determination of palonosetron in human plasma
      and urine has been developed based on liquid chromatography-mass spectrometry.
      The method utilized tramadol as the internal standard (IS). Separation was
      carried out on a Zorbax Eclipse TC-C(18) column using methanol-1mM ammonium
      formate in water (containing 0.1% formic acid, v/v, pH=2.8) as mobile phase for
      gradient elution. Detection is carried out by multiple reaction monitoring (MRM)
      on 3200 Qtrap mass spectrometry. The method has a chromatographic run time of 5.5
      min and is linear within the concentration range 0.01-5.00 ng/mL for plasma and
      0.10-30.00 ng/mL for urine both with a LOD of 0.003 ng/mL. Intra- and inter-day
      RSD of the concentration was 3.66-6.60%, 1.29-7.71% for plasma and 2.39-5.76%,
      2.06-7.13% for urine. The relative error (RE) was -4.58% to 3.26% for plasma and 
      1.47% to 2.53% for urine. The recovery rates of palonosetron and IS both for
      plasma and urine were more than 90%. Palonosetron was stable under all the
      conditions tested. The method was successfully used to analyze palonosetron in
      human plasma and urine over a period of 168 h after intravenously pumping a
      single dose of 0.25mg to volunteers. No significant differences were found
      between the pharmacokinetic parameters and urine accumulated excretory rate for
      male and female volunteers (P>0.05). A two-compartment model was obtained after
      administrations. Palonosetron was eliminated at a slow rate in volunteers. The
      mean urine accumulated excretory rate was 25.97 +/- 12.87%. Inter-individual
      differences could not be neglected due to the high coefficient of variety in
      several pharmacokinetic parameters and the urine accumulated excretion.

PMID- 22465200
TI  - Application of high-speed counter-current chromatography coupled with a reverse
      micelle solvent system to separate three proteins from Momordica charantia.
AB  - High-speed counter-current chromatography (HSCCC) coupled with a reverse micelle
      solvent system was successfully developed to separate three proteins from
      Momordica charantia. Suitable HSCCC conditions were carefully optimized as
      follows: the stationary phase was a reverse micellar phase composed of isooctane
      and 50mM bis-(2-ethylhexyl)-1-sulfosuccinate sodium (AOT). The mobile phase
      contained mobile phase A (50mM Tris-HCl buffer containing 50mM KCl at pH 7.0) for
      forward-extraction and mobile phase B (50mM Tris-HCl buffer containing 0.5M KCl
      at pH 10.0) for back-extraction. The flow rate, detection wavelength and column
      temperature were set at 1.5 ml/min, 280 nm and 4  degrees C, respectively. Under
      these conditions, three fractions (I, II and III) were separated, which showed
      high purity when analyzed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE). The structures of these proteins were then identified
      by MALDI-TOF/TOF-MS/MS and compared with the NCBInr database. Fractions I and III
      were identified as resistance-like protein P-B and pentatricopeptide repeat
      containing protein, respectively, which were found in M. charantia for the first
      time. However, fraction II, which is thought to be a new protein, was not
      identified, and further investigations on this fraction are required. The
      anticancer activities of these three proteins on the human gastric cancer cell
      line SGC-7901 were evaluated in vitro. The results indicated that fraction II has
      excellent anticancer activity (IC(50)=0.116 mg/ml for 48 h treatment). This is
      the first report on the use of HSCCC to isolate proteins from M. charantia.

PMID- 22465201
TI  - A new screening method for proteinuria using Erythrosin B and an automated
      analyzer--rapid, sensitive and inexpensive determination.
AB  - BACKGROUND: In spite of the urgent necessity for a screening test of urinary
      protein for the early diagnosis of kidney diseases, a rapid, accurate and cost
      effective method for their detection has yet to be developed. METHODS: A solution
      containing a buffer agent (pH 2.3) and surfactants and a solution of Erythrosin B
      are added to a urine sample. After letting the mixture stand for 5 min at 37
      degrees C, the dye-bound protein is measured by a spectrophotometer at 546 nm
      using a Hitachi 7170S automated analyzer. RESULTS: The calibration curve was
      linear with human serum albumin concentration in the range of 2.4-200 mg/l. The
      detection limit, 2.4 mg/l was superior to conventional dye-binding methods by one
      order of magnitude and comparable to the turbidimetric immunoassay (TIA). Spot
      urine samples from 70 patients who showed (-) or (+/-) in the dip-stick screening
      test for proteinuria and 79 healthy volunteers were analyzed. There was an
      excellent correlation (r=0.978, n=149) between the results given by the proposed
      method and those by the TIA. CONCLUSIONS: This method provides a viable
      alternative to the conventional immunoassay-based methods for urinary protein
      measurement, and will be useful in the diagnosis of early stage kidney disease.

PMID- 22465202
TI  - Adeno-associated virus (AAV) gene therapy for neurological disease.
AB  - Diseases of the central nervous system (CNS) have provided enormous opportunities
      for the therapeutic application of viral vector gene transfer. Adeno-associated
      virus (AAV) has been the vector of choice in recent clinical trials of
      neurological disease, including Parkinson's and Alzheimer's disease, due to the
      safety, efficacy, and stability of AAV gene transfer to the CNS. This review
      highlights the strategies employed for improving direct and peripheral targeting
      of therapeutic vectors to CNS tissue, and considers the significance of cellular
      and tissue transduction specificity, transgene regulation, and other variables
      that influence achievement of successful therapeutic goals. This article is part
      of the Special Issue entitled 'New Targets and Approaches to the Treatment of
      Epilepsy'.

PMID- 22465203
TI  - Benzodiazepine-induced anxiolysis and reduction of conditioned fear are mediated
      by distinct GABAA receptor subtypes in mice.
AB  - GABA(A) receptor modulating drugs such as benzodiazepines (BZs) have been used to
      treat anxiety disorders for over five decades. In order to determine whether the
      same or different GABA(A) receptor subtypes are necessary for the anxiolytic-like
      action of BZs in unconditioned anxiety and conditioned fear models, we
      investigated the role of different GABA(A) receptor subtypes by challenging wild
      type, alpha1(H101R), alpha2(H101R) and alpha3(H126R) mice bred on the C57BL/6J
      background with diazepam or chlordiazepoxide in the elevated plus maze and the
      fear-potentiated startle paradigms. Both drugs significantly increased open arm
      exploration in the elevated plus maze in wild type, alpha1(H101R) and
      alpha3(H126R), but this effect was abolished in alpha2(H101R) mice; these were
      expected results based on previous published results. In contrast, while
      administration of diazepam and chlordiazepoxide significantly attenuated fear
      potentiated startle (FPS) in wild type mice and alpha3(H126R) mice, the fear
      reducing effects of these drugs were absent in both alpha1(H101R) and
      alpha2(H101R) point mutants, indicating that both alpha1- and alpha2-containing
      GABA(A) receptors are necessary for BZs to exert their effects on conditioned
      fear responses. Our findings illustrate both an overlap and a divergence between
      the GABA(A) receptor subtype requirements for the impact of BZs, specifically
      that both alpha1- and alpha2-containing GABA(A) receptors are necessary for BZs
      to reduce conditioned fear whereas only alpha2-containing GABA(A) receptors are
      needed for BZ-induced anxiolysis in unconditioned tests of anxiety. This raises
      the possibility that GABAergic pharmacological interventions for specific anxiety
      disorders can be differentially tailored.

PMID- 22465204
TI  - Adoptive transfer of bone marrow CD8 T lymphocytes confers full protection vs.
      tumor growth in M-MSV/MuLV experimental model.

PMID- 22465205
TI  - Insulin growth factor adjustment in preimplantation rabbit blastocysts and
      uterine tissues in response to maternal type 1 diabetes.
AB  - Insulin-like growth factors (IGFs) are well-known regulators of embryonic growth
      and differentiation. IGF function is closely related to insulin action. IGFs are
      available to the preimplantation embryo through maternal blood (endocrine
      action), uterine secretions (paracrine action) and by the embryo itself
      (autocrine action). In rabbit blastocysts, embryonic IGF1 and IGF2 are
      specifically strong in the embryoblast (ICM). Signalling of IGFs and insulin in
      blastocysts follows the classical pathway with Erk1/2 and Akt kinase activation.
      The aim of this study was to analyse signalling of IGFs in experimental insulin
      dependent diabetes (exp IDD) in pregnancy, employing a diabetic rabbit model with
      uterine hypoinsulinemia and hyperglycaemia. Exp IDD was induced in female rabbits
      by alloxan treatment prior to mating. At 6 days p.c., the maternal and embryonic
      IGFs were quantified by RT-PCR and ELISA. In pregnant females, hepatic IGF1
      expression and IGF1 serum levels were decreased while IGF1 and IGF2 were
      increased in endometrium. In blastocysts, IGF1 RNA and protein was approx. 7.5
      fold and 2-fold higher, respectively, than in controls from normoglycemic
      females. In cultured control blastocysts supplemented with IGF1 or insulin in
      vitro for 1 or 12 h, IGF1 and insulin receptors as well as IGF1 and IGF2 were
      downregulated. In cultured T1D blastocysts activation of Akt and Erk1/2 was
      impaired with lower amounts of total Akt and Erk1/2 protein and a reduced
      phosphorylation capacity after IGF1 supplementation. Our data show that the IGF
      axis is severely altered in embryo-maternal interactions in exp IDD pregnancy.
      Both, the endometrium and the blastocyst produce more IGF1 and IGF2. The
      increased endogenous IGF1 and IGF2 expression by the blastocyst compensates for
      the loss of systemic insulin and IGF. However, this counterbalance does not fill
      the gap of the reduced insulin/IGF sensitivity, leading to a developmental delay
      of blastocysts in exp IDD pregnancy.

PMID- 22465207
TI  - Brain activity while reading words and pseudo-words: a comparison between
      dyslexic and fluent readers.
AB  - In recent years many studies have focused on brain activity differences between
      fluent and dyslexic readers in order to understand the neural basis of dyslexia.
      The aim of the current study was to examine the processing of words and pseudo
      words in the two hemispheres among dyslexic as compared to fluent readers, using
      behavioral, and electrophysiological source estimation measures. Two matched
      groups of university students, fluent and dyslexic readers, performed a lexical
      decision task in order to examine the processes of word recognition. Dyslexic
      readers showed overall less activity than fluent readers, mainly during late
      processing stages. In addition, the distinctive patterns of activity for words
      and pseudo-words displayed by fluent readers were not apparent in dyslexic
      readers. In particular, the increased activation of left-hemisphere language
      areas found in response to pseudo-words was absent in dyslexics. These findings
      are further evidence of orthographic and phonological impairments in dyslexia.

PMID- 22465206
TI  - Specific dimensions of perceived support and ambulatory blood pressure: which
      support functions appear most beneficial and for whom?
AB  - Perceived support has been related to lower cardiovascular morbidity and
      mortality. However, little is known about the specific functional components of
      support responsible for such links. We tested if emotional, informational,
      tangible, and belonging support predicted ambulatory blood pressure (ABP) and
      interpersonal interactions (e.g., responsiveness), and if such links were
      moderated by gender. In this study, 94 married couples underwent 12 h of ABP
      monitoring during daily life which included a night at home with their spouse.
      They completed a short-form of the interpersonal support evaluation list that
      provides information on total (global) support, as well as specific dimensions of
      support. Results revealed that global support scores did not predict ABP during
      daily life. However, separating out distinct support components revealed that
      emotional support was a significant predictor of lower ambulatory systolic and
      diastolic blood pressure, primarily for women. Finally, emotional support
      predicted greater partner responsiveness and self-disclosure, along with less
      perceived partner negativity although these results were not moderated by gender.
      These data are discussed in terms of the importance of considering specific
      support components and the contextual processes that might influence such links.

PMID- 22465208
TI  - Angiogram-negative subarachnoid hemorrhage: outcomes data and review of the
      literature.
AB  - Spontaneous subarachnoid hemorrhage (SAH) is most commonly caused by rupture of a
      saccular aneurysm or other structural pathologies. Occasionally, no structural
      cause for the hemorrhage can be identified by radiographic imaging. These
      hemorrhages, termed angiogram-negative SAH, are generally considered to have a
      better prognosis than aneurysmal SAH. Angiogram-negative SAH subgroups include
      benign perimesencephalic SAH (PMH) and aneurysmal-type SAH. Outcome data for
      these subgroups differ from those for the group as a whole. We report data for 31
      patients who presented to our institution from 2006 to the present. We performed
      a retrospective chart review, and report outcome data that include rates of
      rehemorrhage, hydrocephalus, vasospasm, permanent ischemic deficits, headaches,
      and outcomes based on modified Rankin Scale scores. We also performed a review of
      the literature and meta-analysis of the data therein. We compared rates of
      complications in the PMH subgroup and the diffuse-type hemorrhage subgroup. The
      chart review revealed no poor outcomes and no rehemorrhages in the patients with
      PMH. In the diffuse hemorrhage subgroup, 1 patient had a rehemorrhage and 2
      patients had a poor outcome. Our literature review found an OR of 6.23 for a good
      outcome for PMH versus diffuse-type hemorrhage, and an OR of 2.78 for
      rehemorrhage in PMH versus diffuse-type hemorrhage. Angiogram-negative SAH is not
      a benign entity. Complications are present but are significantly reduced, and
      outcomes are improved, compared with aneurysmal SAH. 

PMID- 22465209
TI  - Regional differences in emergency medical services use for patients with acute
      stroke (findings from the National Hospital Ambulatory Medical Care Survey
      Emergency Department Data File).
AB  - BACKGROUND: Our objectives were to describe the proportion of stroke patients who
      arrive by ambulance nationwide and to examine regional differences and factors
      associated with the mode of transport to the emergency department (ED). METHODS:
      Patients with a primary discharge diagnosis of stroke based on previously
      validated International Classification of Disease, 9th revision codes were
      abstracted from the National Hospital Ambulatory Medical Care Survey for the
      years 2007 to 2009. We excluded subjects<18 years of age and those with missing
      data. Using logistic regression, we identified independent predictors of arrival
      by ambulance to the ED. RESULTS: Overall, 566 patients met the entry criteria,
      representing 2,153,234 patient records nationally, based on 2010 US census data.
      Of these, 50.4% arrived by ambulance. After adjustment for potential confounders,
      age was associated with use of an ambulance. In addition, patients residing in
      the west and south had lower odds of arriving by ambulance for stroke when
      compared to northeast (South: odds ratio [OR] 0.45 and 95% confidence interval
      [CI] 0.26-0.76; West: OR 0.45 and 95% CI 0.25-0.84; Midwest: OR 0.56 and 95% CI
      0.31-1.01). Compared to the Medicare population, privately insured and self
      insured patients had lower odds of arriving by ambulance (OR for private
      insurance 0.48 and 95% CI 0.28-0.84; OR for self-payers 0.36 and 95% CI 0.14
      0.93). Gender, race, urban or rural location of ED, and safety net status was not
      independently associated with ambulance use. CONCLUSIONS: Patients with stroke
      arrive by ambulance more frequently in the Northeast than in other regions of the
      United States. Identifying reasons for this difference may be useful in improving
      stroke care.

PMID- 22465210
TI  - Liposomes, lipid biophysics, and sphingolipid research: from basic to translation
      research.

PMID- 22465211
TI  - Analysis of plant galactolipids by reversed-phase high-performance liquid
      chromatography/mass spectrometry with accurate mass measurement.
AB  - The composition of plant membrane lipids was investigated by reversed-phase high
      performance liquid chromatography mass spectrometry with accurate mass
      measurement. The data dependent methods for the analysis of
      monogalactosyldiacylglycerols (MGDGs) and digalactosyldiacylglycerols (DGDGs)
      have been developed. The optimised chromatographic systems were based on a 2.0 mm
      i.d. Nucleosil C18 column with methanol/water (MGDGs) or
      acetonitrile/methanol/water (DGDGs) gradients. The galactolipids were ionised by
      electrospray operated in the positive ion mode and identified based on their
      MS/MS spectra. High resolution spectra with accurate masses were found to be
      essential for correct interpretation of the MS data. The elution order of non
      oxidised MGDGs and DGDGs followed the equivalent carbon numbers. The methods were
      applied for detailed characterisation of the MGDGs and DGDGs in the leaves of
      Arabidopsis thaliana and Melissa officinalis.

PMID- 22465212
TI  - Eosinophilic esophagitis: epithelial mesenchymal transition contributes to
      esophageal remodeling and reverses with treatment.
AB  - BACKGROUND: Mechanisms underlying esophageal remodeling with subepithelial
      fibrosis in subjects with eosinophilic esophagitis (EoE) have not been
      delineated. OBJECTIVES: We sought to explore a role for epithelial mesenchymal
      transition (EMT) in subjects with EoE and determine whether EMT resolves with
      treatment. METHODS: Esophageal biopsy specimens from 60 children were
      immunostained for epithelial (cytokeratin) and mesenchymal (vimentin) EMT
      biomarkers, and EMT was quantified. Subjects studied had EoE (n = 17),
      indeterminate EoE (n = 15), gastroesophageal reflux disease (n = 7), or normal
      esophagus (n = 21). EMT was analyzed for relationships to diagnosis, eosinophil
      counts, and indices of subepithelial fibrosis, eosinophil peroxidase, and TGF
      beta immunostaining. EMT was assessed in pretreatment and posttreatment biopsy
      specimens from 18 subjects with EoE treated with an elemental diet, 6-food
      elimination diet, or topical corticosteroids (n = 6 per group). RESULTS: TGF
      beta1 treatment of esophageal epithelial cells in vitro for 24 hours induced
      upregulation of mesenchymal genes characteristic of EMT, including N-cadherin
      (3.3-fold), vimentin (2.1-fold), and fibronectin (7.5-fold). EMT in esophageal
      biopsy specimens was associated with EoE (or indeterminate EoE) but not
      gastroesophageal reflux disease or normal esophagus and was correlated to
      eosinophil counts (r = 0.691), eosinophil peroxidase (r = 0.738), and TGF-beta (r
      = 0.520) immunostaining and fibrosis (r = 0.644) indices. EMT resolved with EoE
      treatments that induced clinicopathologic remission with reduced eosinophil
      counts. EMT decreased significantly after treatment by 74.1% overall in the 18
      treated subjects with EoE; pretreatment versus posttreatment EMT scores were 3.17
      +/- 0.82 versus 0.82 +/- 0.39 (P < .001), with similar decreases within treatment
      groups. Pretreatment/posttreatment EMT was strongly correlated with eosinophil
      counts for combined (r = 0.804, P < .001) and individual treatment groups.
      CONCLUSIONS: EMT likely contributes to subepithelial fibrosis in subjects with
      EoE and resolves with treatments that decrease esophageal inflammation, and its
      resolution correlates with decreased numbers of esophageal eosinophils.

PMID- 22465213
TI  - Induction and suppression of allergic diarrhea and systemic anaphylaxis in a
      murine model of food allergy.
AB  - BACKGROUND: The clinical manifestations of food allergy include diarrhea and
      systemic anaphylaxis (shock), which can occur together or by themselves in
      different subjects. Although ingested food antigens need to be absorbed to induce
      shock, it is not known whether they need to be absorbed to induce diarrhea.
      OBJECTIVE: We sought to identify mechanisms that determine whether food allergy
      induces diarrhea versus shock and determine whether diarrhea requires absorption
      of ingested antigens. METHODS: These issues were studied in mice in active,
      passive, and hybrid immunization models. The active model was used to determine
      the allergic diarrhea susceptibility of J chain- and polymeric immunoglobulin
      receptor-deficient mice, which are unable to secrete IgA. The hybrid model was
      used to determine whether intravenously administered antigen-specific IgG
      antibody, which is not secreted into the gut, can protect against allergic
      diarrhea, as well as shock. RESULTS: Shock, but not diarrhea, was induced in
      naive mice by using intravenous IgE anti-trinitrophenyl (TNP) antibody, followed
      by oral TNP-BSA, whereas both were induced in mice presensitized with
      intraperitoneal ovalbumin/alum plus oral ovalbumin. More TNP-BSA was required to
      induce shock than diarrhea in presensitized mice, and intravenous IgG anti-TNP
      antibody, which is not secreted into the gut, protected these mice against both
      diarrhea and shock. Consistent with this, chicken ovalbumin-immunized J chain-
      and polymeric immunoglobulin receptor-deficient mice, which have high serum IgA
      levels but little intestinal IgA, resisted diarrhea induction. CONCLUSION:
      Intestinal immunity and oral antigen dose determine whether diarrhea, systemic
      anaphylaxis, or both are induced, and ingested antigen must be absorbed to induce
      either response.

PMID- 22465215
TI  - Steroidal saponins from Smilacina japonica.
AB  - Three new steroidal saponins, japonicoside A (1), japonicoside B (2) and
      japonicoside C (3) were isolated from the dried rhizomes and roots of Smilacina
      japonica A. Gray. Their structures were elucidated as (25S)-5alpha-spirostan
      9(11)-en-3beta-ol 3-O-beta-D-glucopyranosyl-(1->2)-[beta-D-xylopyranosyl-(1->3)]
      beta-D-glucopyranosyl-(1->4)-beta-D-galactopyranoside (1), (25S)-5alpha-spirostan
      9(11)-en-3beta,17alpha-diol 3-O-beta-D-glucopyranosyl-(1->2)-[beta-D
      xylopyranosyl-(1->3)]-beta-D-glucopyranosyl-(1->4)-beta-D-galactopyranoside (2)
      and (25S)-5alpha-spirostan-9(11)-en-3beta,17alpha,24alpha-triol 3-O-beta-D
      glucopyranosyl-(1->2)-[beta-D-xylopyranosyl-(1->3)]-beta-D-glucopyranosyl-(1->4)
      beta-D-galactopyranoside (3) on the basis of chemical methods and detailed
      spectroscopic analysis, including 1D, 2D NMR and HR-ESI-MS. The cytotoxicity of
      isolated compounds was evaluated in vitro for cytotoxic properties against human
      hepatocellular carcinoma cells (SMMC-7221) and human colorectal adenocarcinoma
      cells (DLD-1), respectively.

PMID- 22465216
TI  - Participation of cholinergic pathways in alpha-hederin-induced contraction of rat
      isolated stomach strips.
AB  - The dry extract of Hedra helix leaves and its main active compounds,
      predominantly alpha-hederin and hederacoside C, has been traditionally believed
      to act spasmolytic. However, it has been recently proved that both, the extract
      of ivy and triterpenoid saponins, exhibit strong contractile effect on rat
      isolated stomach smooth muscle strips. It turned out that the most potent
      contractile agent isolated from the extract of ivy leaves is alpha-hederin. Thus,
      it seems reasonable to estimate the mechanism of the contractile effect of this
      saponin. The presented study was aimed at verifying the participation of
      cholinergic pathways (muscarinic and nicotine receptors) in alpha-hederin-induced
      contraction. The experiments were carried out on rat isolated stomach corpus and
      fundus strips under isotonic conditions. The preparations were preincubated with
      either atropine or hexamethonium and then exposed to alpha-hederin. All results
      are expressed as the percentage of the response to acetylcholine - a reference
      contractile agent. The obtained results revealed that the pretreatment of
      isolated stomach strips (corpus and fundus) with atropine neither prevented nor
      remarkably reduced the reaction of the preparations to alpha-hederin. Similarly,
      if the application of saponin was preceded by the administration of
      hexamethonium, the strength of the contraction of stomach fundus strips induced
      by alpha-hederin was not modified. Concluding, it can be assumed that the
      cholinergic pathways do not participate in alpha-hederin-evoked contraction of
      rat isolated stomach preparations.

PMID- 22465214
TI  - Methacholine challenge test: diagnostic characteristics in asthmatic patients
      receiving controller medications.
AB  - BACKGROUND: The methacholine challenge test (MCT) is commonly used to assess
      airway hyperresponsiveness, but the diagnostic characteristics have not been well
      studied in asthmatic patients receiving controller medications after the use of
      high-potency inhaled corticosteroids became common. OBJECTIVES: We investigated
      the ability of the MCT to differentiate participants with a physician's diagnosis
      of asthma from nonasthmatic participants. METHODS: We conducted a cohort-control
      study in asthmatic participants (n= 126) who were receiving regular controller
      medications and nonasthmatic control participants (n= 93) to evaluate the
      sensitivity and specificity of the MCT. RESULTS: The overall sensitivity was 77%
      and the specificity was 96% with a threshold PC(20) (the provocative
      concentration of methacholine that results in a 20% drop in FEV(1)) of 8 mg/mL.
      The sensitivity was significantly lower in white than in African American
      participants (69% vs 95%, P= .015) and higher in atopic compared with nonatopic
      (82% vs 52%, P= .005). Increasing the PC(20) threshold from 8 to 16 mg/mL did not
      noticeably improve the performance characteristics of the test. African American
      race, presence of atopy, and lower percent predicted FEV(1) were associated with
      a positive test result. CONCLUSIONS: The utility of the MCT to rule out a
      diagnosis of asthma depends on racial and atopic characteristics. Clinicians
      should take into account the reduced sensitivity of the MCT in white and
      nonatopic asthmatic patients when using this test for the diagnosis of asthma.

PMID- 22465217
TI  - Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong
      remodeling of our epigenomes.
AB  - Cancer, as one of the non-communicable diseases, remains one of the leading
      causes of death around the world. Recently, epigenetic changes in DNA methylation
      patterns at CpG sites (epimutations) or deregulated chromatin states of tumor
      promoting genes and noncoding RNAs emerged as major governing factors in tumor
      progression and cancer drug sensitivity. Furthermore, various environmental
      factors such as nutrition, behavior, stress, and toxins remodel our epigenomes
      lifelong in a beneficial or detrimental way. Since epigenetic marks
      (epimutations) are reversible in contrast to genetic defects, chemopreventive
      nutritional polyphenols (soy, genistein, resveratrol, catechin, curcumin) are
      currently evaluated for their ability to reverse adverse epigenetic marks in
      cancer (stem) cells to attenuate tumorigenesis-progression, prevent metastasis or
      sensitize for drug sensitivity. Although polyphenols in fruit and vegetables may
      help to reduce the risk of cancer, few protective effects have been firmly
      established, presumably because of inappropriate timing or dosing of diet
      exposure or due to confounding factors such as smoking and alcohol. In this
      review will discuss the possible epigenetic contributions of dietary polyphenols
      in cancer chemoprevention.

PMID- 22465218
TI  - Selective inhibition of MMP-9 gene expression by mangiferin in PMA-stimulated
      human astroglioma cells: involvement of PI3K/Akt and MAPK signaling pathways.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which play a
      key role in invasion, migration, and angiogenesis of astrogliomas and other
      malignant tumors. Thus, controlling MMPs has been considered an important
      therapeutic strategy for prevention and/or treatment of gliomas. However, most
      MMP inhibitors developed so far are broad spectrum inhibitors; thus, it is
      necessary to develop a selective MMP inhibitor to minimize potential side
      effects. In the present study, we found that mangiferin, a glucosylxanthone
      isolated from Anemarrhena asphodeloides, specifically inhibited MMP-9 gene
      expression in phorbol myristate acetate (PMA)-stimulated human astroglioma U87MG,
      U373MG, and CRT-MG cells. However, it did not affect other MMPs, such as MMP-1, 
      2, -3, and -14. Mangiferin suppressed MMP-9 expression at the promoter, mRNA, and
      protein levels and additionally inhibited MMP-9 enzymatic activity. The Matrigel
      invasion assay showed that mangiferin suppresses the in vitro invasiveness of
      glioma cells, which appears to be correlated with mangiferin-mediated MMP-9
      inhibition. Further mechanistic studies demonstrated that mangiferin inhibits the
      binding of NF-kappaB and AP-1 to the MMP-9 promoter and suppresses the PMA
      induced phosphorylation of Akt and MAP kinases, which are upstream signaling
      molecules in MMP-9 expression. Thus, the specific inhibition of MMP-9 by
      mangiferin may provide a valuable pharmacological tool for treatment of gliomas.

PMID- 22465219
TI  - Angiotensin II type 2 receptor-dependent increase in nitric oxide synthase
      activity in the endothelium of db/db mice is mediated via a MEK pathway.
AB  - Angiotensin II type 2 receptor (AT(2)R) stimulation may cause vasodilation. It
      could thereby contribute to the antihypertensive effects of angiotensin II type 1
      receptor (AT(1)R) antagonists since AT(1)R blockade reportedly increases
      endogenous levels of Ang II, and this may then bind to the unblocked AT(2)R.
      Because this is potentially an important consideration in diabetes, we examined
      whether or not AT(2)R mediates vasorelaxation in db/db diabetic mice. We also
      examined if AT(2)R-mediated vasorelaxation is preserved after long-term treatment
      with the AT(1)R antagonist losartan. The effects of AT(2)R stimulation, with
      either Ang II or the selective agonist CGP-42112A, were studied in aortas from
      db/db mice (a type 2 diabetic model). CGP-42112A induced a concentration
      dependent relaxation in db/db aortas (not in Lean aortas), and this was
      significantly weakened by the MEK-inhibitor PD98059. CGP-42112A-induced
      relaxations were increased by Ang II-stimulation (by the organ-culture method) or
      by AT(1)R blockade (by long-term losartan treatment) only in Lean aortas. Basal
      AT(2)R expression, and Ang II-stimulated MEK and eNOS phosphorylations were all
      increased in aortas from db/db (vs. Lean) mice. Long-term losartan treatment
      increased Ang II-stimulated MEK and eNOS phosphorylations in aortas from Lean,
      but not db/db, mice. Therefore, this study has provided evidence that AT(2)R
      mediated NO production and vasorelaxation through a MEK pathway are enhanced
      (under basal conditions) in aortas from db/db (vs. Lean) mice. The preservation
      of such AT(2)R function during AT(1)R blockade needs to be considered in the
      search for a physiological role for AT(2)R.

PMID- 22465221
TI  - Evaluation of four RNA extraction methods for gene expression analyses of
      Cryptosporidium parvum and Toxoplasma gondii oocysts.
AB  - Cryptosporidium spp. and Toxoplasma gondii are important coccidian parasites that
      have caused waterborne and foodborne disease outbreaks worldwide. Techniques like
      subtractive hybridization, microarrays, and quantitative reverse transcriptase
      real-time polymerase chain reaction (RT-qPCR) assays have been used to understand
      the roles of specific genes in regulating life stage development and pathogenesis
      of these parasites. Key to the success of these approaches is isolating high
      quality messenger RNA (mRNA), which is particularly difficult with coccidian
      oocysts. Although commercial kits can provide high quality mRNA to study gene
      expressions in mammalian cells, their performances have not been thoroughly
      evaluated on oocysts. In this study, four RNA extraction kits: RiboPure-bacteria,
      MasterPure RNA, RNeasy micro, and TRIzol LS reagent kits were evaluated for their
      ability to isolate high quality mRNA. Results revealed that all four kits easily
      isolated total RNA from C. parvum oocysts. Analysis of total RNA quality as
      measured by RNA integrity number (RIN) showed sufficiently high quality values
      ranging from 8.4 to 9.8. However, genomic DNA (gDNA) contamination was present in
      all extracts. Additional DNase I treatment effectively removed gDNA contaminants,
      but partially degraded the RNA (RIN=5.0-7.7). Total RNA isolations from T. gondii
      oocysts were also attempted and were partially successful, yielding RNA extracts
      sufficient for only RT-qPCR. Overall, the RNeasy micro kit with additional DNase
      I treatment was the most effective for extracting sufficiently high quality total
      RNA from C. parvum and T. gondii oocysts.

PMID- 22465222
TI  - Medium-throughput profiling method for screening polysaccharide-degrading enzymes
      in complex bacterial extracts.
AB  - Polysaccharides are the most abundant and the most diverse renewable materials
      found on earth. Due to the stereochemical variability of carbohydrates,
      polysaccharide-degrading enzymes - i.e. glycoside hydrolases and polysaccharide
      lyases - are essential tools for resolving the structure of these complex
      macromolecules. The exponential increase of genomic and metagenomic data
      contrasts sharply with the low number of proteins that have ascribed functions.
      To help fill this gap, we designed and implemented a medium-throughput profiling
      method to screen for polysaccharide-degrading enzymes in crude bacterial
      extracts. Our strategy was based on a series of filtrations, which are absolutely
      necessary to eliminate any reducing sugars not directly generated by enzyme
      degradation. In contrast with other protocols already available in the
      literature, our method can be applied to any panel of polysaccharides having
      known and unknown structures because no chemical modifications are required. We
      applied this approach to screen for enzymes that occur in Pseudoalteromonas
      carrageenovora grown in two culture conditions.

PMID- 22465220
TI  - High urinary levels of resveratrol metabolites are associated with a reduction in
      the prevalence of cardiovascular risk factors in high-risk patients.
AB  - Moderate wine consumption has been shown to reduce cardiovascular (CV) risk, due
      to alcohol and polyphenolic compounds, such as resveratrol. We investigated the
      associations between total urinary resveratrol metabolites (TRMs) as biomarkers
      of wine and resveratrol consumption and CV risk factors in a large cross
      sectional study including high CV risk individuals in Spain. We studied 1000
      participants in the PREDIMED Study in whom TRMs were analyzed by LC-MS/MS with a
      previous solid phase extraction. Multiple linear regression of TRMs (biomarker of
      wine consumption) improved the mean (95% CI) of HDL [0.168 (0.027-0.309); P=0.02]
      and triglyceride [-1.012 (-1.797 to -0.227); P=0.012] plasma concentrations and
      heart rate [-0.259 (-0.412 to -0.107); P<0.001]. Models of TRMs adjusted for
      alcohol (biomarker of resveratrol intake) decreased fasting blood glucose [-0.533
      (-1.034 to -0.033); P=0.037] and triglyceride [-1.014 (-1.998 to -0.029);
      P=0.044] concentrations, and heart rate [-0.277 (-0.467 to -0.087); P=0.004].
      Both resveratrol and wine intake, evaluated as TRMs, were associated with
      beneficial changes in blood lipid profiles, fasting blood glucose (only
      resveratrol) and heart rate, suggesting that resveratrol intake via wine
      consumption might help to decrease CV risk factors.

PMID- 22465223
TI  - Effects of soft tissue injury to the temporomandibular joint: report of 8 cases.
AB  - Our aim was to describe the effects of soft tissue injury to the
      temporomandibular joint (TMJ), to analyse possible reasons for it, and to
      evaluate the results of treatment. Eight patients (12 joints) who developed
      disorders of the TMJ after trauma to the mandible without fracture of the condyle
      were treated in our department from 2009 to 2010. Magnetic resonance imaging
      (MRI) and computed tomography (CT) were used to check the condition of the joint.
      Five patients had their joints explored to relieve pain and improve mouth
      opening. MRI showed all 12 joints had displaced discs. CT showed that the surface
      of the condylar bone was "intact" immediately after injury but destroyed later in
      8 joints. Exploration showed fibrous ankylosis in 5, osteoarthritis with intra
      articular adhesions in 2, and internal derangement in 1. Four were treated by
      costochondral graft (CCG) with 7 symptomatic joints. The disc was repositioned in
      1 case with 1 affected joint. The mean maximal incision opening at follow-up were
      significantly better than the one before treatment (mean 34 compared with 23 mm,
      p=0.02). Pain in the TMJ was relieved by operation in all patients so treated.
      The other 3 patients (4 joints) had no treatment because their symptoms were
      minor and mouth opening was not restricted. Soft tissue injuries of the TMJ can
      potentially lead to internal derangement, osteoarthrosis, and possibly fibrous
      ankylosis, which should be considered during follow-up. Displacement of the disc
      and damage to the condylar cartilage seem to be the causes of these
      complications. Surgical management is effective in the short term.

PMID- 22465224
TI  - Response to "Tuberculosis of the temporomandibular joint: part of a bigger
      picture".

PMID- 22465225
TI  - Tumor tissue inhibitor of metalloproteinases-1 (TIMP-1) in hormone-independent
      breast cancer might originate in stromal cells, and improves stratification of
      prognosis together with nodal status.
AB  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) is shown to be a potential
      marker for poor prognosis in breast cancer, but the biology of TIMP-1 is only
      partially understood. In this study, TIMP-1 production was studied in a co
      culture model of hormone-independent breast cancer cell lines and mesenchymal
      stem cells mimicking the stromal components of the tumor. In addition, the
      prognostic value of TIMP-1 was histologically evaluated in a clinical material of
      168 patients with hormone-independent breast tumors. The hormone-independent
      breast cancer (BC) cell lines MDA-MB-231, M4A4 and NM2C5 did not produce TIMP-1
      protein in measureable quantities. Six tested primary mesenchymal stem cell lines
      all produced TIMP-1. Co-culturing of mesenchymal stem cells and breast cancer
      cells resulted in positive immunocytochemical diffuse staining for TIMP-1 for
      both cell types. Culturing breast cancer cells with MSC-conditioned media
      resulted in a positive cytoplasmic immunoreactivity for TIMP-1, and TIMP-1
      protein concentration in cell lysates increased 2.7-fold (range 1.1-4.7). The
      TIMP-1 mRNA levels remained unaffected in BC cells. This might suggest that
      breast cancer cells can take up TIMP-1 produced by stromal cells and are thus
      displaying cellular immunoreactivity. In addition, TIMP-1 was shown to improve
      stratification of prognosis in clinical material.

PMID- 22465226
TI  - Lysosomal pathways to cell death and their therapeutic applications.
AB  - Lysosomes are the major cell digestive organelles that were discovered over 50
      years ago. They contain a number of hydrolases that help them to degrade
      intracellular and extracellular material delivered. Among the hydrolases, the
      cathepsins, a group of proteases enclosed in the lysosomes, have a major role.
      About a decade ago, the cathepsins were found to participate in apoptosis.
      Following their release into the cytosol, they cleave Bid and degrade
      antiapoptotic Bcl-2 proteins, thereby triggering the mitochondrial pathway of
      apoptosis, with the lysosomal membrane permeabilization being the critical step
      in this pathway. Lysosomal dysfunction is linked with several diseases, including
      cancer and neurodegenerative disorders, thereby providing a potential for
      therapeutic applications. In this review lysosomes and lysosomal proteases
      involvement in apoptosis and their possible pharmaceutical targeting are
      discussed.

PMID- 22465227
TI  - Absence of T and B lymphocytes modulates dystrophic features in dysferlin
      deficient animal model.
AB  - Dysferlin mutations cause muscular dystrophy (dysferlinopathy) characterized by
      adult onset muscle weakness, high serum creatine kinase levels, attenuation of
      muscle regeneration and a prominent inflammatory infiltrate. In order to verify
      the role of lymphocytes and immune cells on this disease, we generated the
      Scid/A/J transgenic mice and compared these animals with the age-matched A/J
      mice. The absence of T and B lymphocytes in this animal model of dysferlinopathy
      resulted in an improvement of the muscle regeneration. Scid/A/J mice showed
      increased specific force in the myosin heavy chain 2A-expressing fibers of the
      diaphragm and abdominal muscles. Moreover, a partial reduction in complement
      deposition was observed together with a diminution in pro-inflammatory M1
      macrophages. Consistent with this model, T and B lymphocytes seem to have a role
      in the muscle damaging immune response. The knowledge of the involvement of
      immune system in the development of dysferlinopathies could represent an
      important tool for their rescuing. By studying Scid/blAJ mice, we showed that it
      could be possible to modulate the pathological symptoms of these diseases by
      interfering with different components of the immune system.

PMID- 22465228
TI  - Prevalence and clinical relevance of enteropathy associated with systemic
      autoimmune diseases.
AB  - OBJECTIVE: To assess whether systemic autoimmune diseases are a risk group for
      coeliac disease and if there is a systemic autoimmune diseases-associated
      enteropathy. METHODS: 183 patients with systemic autoimmune diseases were
      included. Duodenal biopsy was carried out on patients with positive coeliac
      genetics (HLA-DQ2-DQ8) and/or serology and/or symptoms of the coeliac disease
      spectrum. When enteropathy was found, causes, including gluten sensitivity, were
      investigated and categorized according to a sequentially applied treatment.
      Results were analysed with Chi-square or Fisher exact tests. RESULTS: The
      prevalence of coeliac disease with atrophy was 0.55% (1 of 183 patients). Thirty
      eight of the 109 patients (34.8%) who underwent duodenal biopsy had lymphocytic
      enteropathy (8 infectious, 5 due to gluten sensitive enteropathy, 5 HLA-DQ2/DQ8
      who did not accept gluten-free diet and 20 of unknown aetiology). Lymphocytic
      enteropathy was unrelated to disease activity or immunosuppressants. HLA-DQ2 was
      more frequent in connective tissue disease (41.5%) compared with systemic
      vasculitis and autoinflammatory diseases (17.9%) (p=0.02), whereas a lower
      percentage of lymphocytic enteropathy was observed in the former (20.2% vs.
      41.6%). Lymphocytic enteropathy was clinically irrelevant in cases with no
      definite aetiology. DISCUSSION: One third of systemic autoimmune diseases
      patients had enteropathy of uncertain clinical meaning in the majority of cases,
      which was rarely due to gluten sensitive enteropathy.

PMID- 22465229
TI  - The dendritic tree and brain disorders.
AB  - Dendrite morphogenesis is a complex but well-orchestrated process and includes
      the development of dendritic branches, forming characteristic dendrite arbors,
      and dendritic spines, allowing neurons to communicate with each other. Various
      studies report that many neuropsychiatric disorders are characterized by
      dendritic and synaptic pathology, including abnormal spine density and
      morphology, synapse loss, and aberrant synaptic signaling and plasticity. In this
      review, we discuss dendrite development and branching, and in specific,
      morphology, cytoskeletal architecture, and how the complexity of the dendrite
      tree and its functional capabilities are altered in various brain disorders.
      Identifying and understanding these changes in dendrite morphology are essential
      for understanding brain function in normal and disease states.

PMID- 22465230
TI  - Selected physiological effects of ultrafine particles in acute cardiovascular
      morbidity.
AB  - Ultrafine particles (UFPs) have emerged as a potentially important environmental
      health concern as they are produced in large numbers by vehicle emissions and may
      contribute to previously reported associations between traffic pollution and
      acute cardiovascular morbidity. This review examines recent epidemiological
      evidence of UFP exposures and selected physiological outcomes that may be
      modified as part of the underlying causal pathway(s) linking particulate air
      pollution and acute cardiovascular morbidity. Outcomes examined included changes
      in heart rate variability (HRV) (autonomic function), ST-segment depression
      (myocardial ischemia), QT-interval (ventricular repolarization), and endothelial
      vasomotor function. Twenty-two studies were reviewed in total: 10 prospective
      panel studies and 12 randomized cross-over studies. Sixteen studies identified a
      significant relationship between UFPs and at least one of the above outcomes and
      current evidence generally supports the biological plausibility of a relationship
      between UFPs and acute cardiovascular morbidity. However, discrepancies were
      apparent in the direction of observed associations, particularly for HRV and
      ventricular repolarization. Reasons for these discrepancies may include
      differences in particle composition, time-point of clinical evaluation, and
      population susceptibilities. Nevertheless, evidence to date suggests that UFPs
      have a measureable impact on physiological measures known to be altered in cases
      of acute cardiovascular morbidity. Moving forward, expanded use of personal
      exposure measures is recommended for prospective panel studies to minimize
      exposure misclassification. In addition, effort should be made to include more
      women in studies of the acute cardiovascular effects of UFPs as findings to date
      generally reflect responses in men.

PMID- 22465231
TI  - Lysophosphatidic acid induces neurite branch formation through LPA3.
AB  - Although neurite branching is crucial for neuronal network formation after birth,
      its underlying mechanisms remain unclear. Here, we demonstrate that
      lysophosphatidic acid (LPA) stimulates neurite branching through a novel
      signaling pathway. Treatment of neuronal cell lines with LPA resulted in neurite
      branch formation when LPA(3) receptor was introduced. The effects of LPA were
      blocked by inhibition of G(q) signaling. Furthermore, expression of inhibitory
      mutants of the small GTPase Rnd2/Rho7 or an Rnd2 effector rapostlin abolished
      LPA(3)-mediated neurite branching. The LPA(3) agonist 2(S)-OMPT or LPA also
      induced axonal branch formation in hippocampal neurons, which was blocked by G(q)
      and Rnd2 pathway inhibition or LPA(3) knockdown. These findings suggest that the
      novel signaling pathway involving LPA(3), G(q), and Rnd2 may play an important
      role in neuronal network formation.

PMID- 22465233
TI  - Development of a p38delta mitogen activated protein kinase ELISA assay for the
      quantitative determination of inhibitor activity.
AB  - The p38 mitogen activated protein kinase (MAPK) has emerged as a target for
      treating inflammatory diseases, like rheumatoid arthritis (RA). Expression of
      p38delta is induced in rheumatoid arthritis synovial fibroblasts (RASFs) by a
      cytokine-independent pathway substantially different from other MAPK pathways. To
      identify inhibitors of p38delta MAPK, we developed a direct ELISA assay based on
      a previously described p38alpha assay for monitoring the phosphorylation of ATF
      2. This work presents a straightforward assay for evaluating the potency of small
      molecule inhibitors. To validate the assay under optimized conditions, we used
      reference compounds and achieved results comparable to published data.

PMID- 22465232
TI  - What are regulatory T cells (Treg) regulating in cancer and why?
AB  - The role regulatory T cells (Treg) play in cancer development and progression is
      not clear. Earlier evidence suggested that CD4(+)FOXP3(+)CD25(high) Treg
      accumulate in tumors and the peripheral blood of patients with cancer and through
      suppression of anti-tumor immune responses promote tumor growth. However, more
      recent data indicate that in certain cancers, such as colorectal carcinoma (CRC),
      Treg suppress bacteria-driven inflammation which promotes carcinogenesis and thus
      benefit the host. Treg appear to play a dual role in cancer. This might explain
      why the frequency and functions of Treg are associated with a poor prognosis in
      some cancers but with favorable outcome in others. The clinical and prognostic
      significance of Treg in cancer depends on environmental factors, including
      infectious agents, tumor-derived products and locally-produced cytokines, which
      shape the nature of immune responses, including Treg generation, recruitment and
      survival. Adaptive or inducible (i) Treg or Tr1 are the major subset(s) of Treg
      present in cancer. These iTreg are a distinct subset of regulatory cells that
      phenotypically and functionally differ from FOXP3(+) natural (n) Treg responsible
      for peripheral tolerance. They mediate powerful suppression of effector T cells
      via diverse mechanisms, produce immunosuppressive cytokines, notably TGF-beta as
      well as prostaglandin E2 and adenosine, and are resistant to apoptosis or
      oncological therapies. Strategies for silencing of Tr1 in patients with cancer
      will require novel approaches that can selectively deplete these cells or block
      molecular pathways they utilize.

PMID- 22465234
TI  - Prognostic value of matrix metalloproteinase 9 expression in patients with non
      small cell lung cancer.
AB  - BACKGROUND: The role of matrix metalloproteinase 9 (MMP-9) expression in non
      small cell lung cancer (NSCLC) remains controversial. We performed a systematic
      review of the literature with meta-analysis. METHODS: Electronic databases were
      used to identify published studies before December 1, 2011. Pooled hazard ratio
      (HR) with 95% confidence interval (95% CI) was used to estimate the strength of
      the association between MMP-9 expression survival of NSCLC patients.
      Heterogeneity and publication bias were also assessed. RESULTS: The final
      analysis of 2029 NSCLC cases from 17 studies is presented. The combined HR of
      1.84 (95% CI: 1.62-2.09) suggested that MMP-9 over-expression had a poor
      prognosis in patients with NSCLC. Subgroup analyses also detected significant
      association. Heterogeneity and publication bias was absent in current meta
      analysis. Sensitivity analyses suggested that the summary statistics obtained
      should approximate the actual average. CONCLUSION: High MMP-9 expression is
      associated with a poor prognosis in patients with NSCLC.

PMID- 22465235
TI  - Current 25-hydroxyvitamin D assays: do they pass the test?
AB  - BACKGROUND: Vitamin D testing is becoming increasingly important with recent
      research demonstrating a correlation between vitamin D insufficiency and
      metabolic diseases, immunodeficiencies and other diseases. However, existing 25
      hydroxyvitamin D (25OHD) assays lack comparability to the candidate reference
      method, causing difficulties in diagnosis and monitoring of vitamin D deficiency.
      METHODS: We looked at the accuracy of 3 automated assays (Roche Diagnostics
      Elecsys(r) Total 25OHD assay, Abbott Architect(r) Total vitamin D assay, Advia
      Centaur(r) vitamin D Total assay) and Diasorin(r) Radioimmunoassay (RIA) compared
      to a routine laboratory Liquid Chromatography-Tandem Mass Spectrometry (LC
      MS/MS). RESULTS: The correlation based on Passing Bablok regression was good with
      the slopes between 0.95 and 1.31 and the intercepts between -3.24 and 3.68.
      However, a significant positive bias was observed using the Abbott Architect and
      the Diasorin RIA. Using published analytical goals of coefficient of variation
      (CV) <10% and bias <5%, most methods did not meet these criteria. Using
      measurement of uncertainty of 9%, most methods were able to meet criteria using
      quality control materials but not patient samples. CONCLUSION: Inadequacies of
      these assay performances are contributed by differences in method of extraction
      of vitamin D from vitamin D binding protein, cross-reactivities to 25OHD(2),
      25OHD(3) and other vitamin D metabolites, matrix interferences and a lack of
      standardization.

PMID- 22465236
TI  - Unexpected interference of baby wash products with a cannabinoid (THC)
      immunoassay.
AB  - OBJECTIVES: The results of newborn drug screening have far-reaching impact not
      only in healthcare, but also in the legal domain. Therefore, the accuracy of
      these results cannot be undervalued. When false positive cannabinoid (THC)
      screening results for this population were suspected at our institution, a
      multidisciplinary approach was initiated to evaluate the screening process for
      any pre-analytical or analytical sources of error or interference. DESIGN AND
      METHODS: Mixtures of drug-free urine with various commercial products and
      materials that commonly contact newborns in our nursery were prepared and tested
      using the immunoassay screening methods in our laboratory. Additional commercial
      products were similarly tested; and when available, individual surfactants common
      to the interfering products were also evaluated. RESULTS: Addition of Head-to-Toe
      Baby Wash to drug-free urine produced a dose dependent measureable response in
      the THC immunoassay. Addition of other commercially available baby soaps gave
      similar results, and subsequent testing identified specific chemical surfactants
      that reacted with the THC immunoassay. CONCLUSION: We have identified commonly
      used soap and wash products used for newborn and infant care as potential causes
      of false positive THC screening results. Such results in this population can lead
      to involvement by social services or false child abuse allegations. Given these
      consequences, it is important for laboratories and providers to be aware of this
      potential source for false positive screening results and to consider
      confirmation before initiating interventions. Most importantly, we demonstrate
      the need for active involvement in the "total testing process," as sources of
      error are not confined to the laboratory walls.

PMID- 22465237
TI  - Diurnal variation in lipoprotein-associated phospholipase A(2) (Lp-PLA(2)).
AB  - OBJECTIVES: The aim of our study was to determine the diurnal variation of
      lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an arterial-specific
      inflammatory enzyme implicated in the formation of vulnerable, rupture-prone
      plaque that can identify individuals at high risk for cardiovascular disease.
      Presently, the diurnal variation of Lp-PLA(2) is not known. DESIGN AND METHODS:
      Ten men and 8 women (age range: 22-76 years) had a blood sample taken every 4 h
      over a 24-hour time period. Samples were analyzed for both Lp-PLA(2) mass and
      activity. RESULTS: The mean coefficient of variation (CV) for Lp-PLA(2) mass was
      5.9% (ranges from 2.5 to 9.4%) for the 18 subjects. Similarly, the mean CV for Lp
      PLA(2) activity was 3.7% (ranges from 1.2 to 6.8%). There were no significant
      correlations between CV and any of the subject characteristics. CONCLUSIONS: The
      diurnal variation of Lp-PLA(2) mass and activity is similar to that of well
      accepted lipoprotein risk factors. With the relatively low diurnal variability,
      there does not appear to be a need to make sure serial measurements of Lp-PLA(2)
      mass and activity are taken at the same time of the day.

PMID- 22465238
TI  - An overview of the regulation of bone remodelling at the cellular level.
AB  - OBJECTIVES: To review the current literature on the regulation of bone
      remodelling at the cellular level. DESIGN AND METHODS: The cellular activities of
      the cells in the basic multicellular unit (BMU) were evaluated. RESULTS: Bone
      remodelling requires an intimate cross-talk between osteoclasts and osteoblasts
      and is tightly coordinated by regulatory proteins that interact through complex
      autocrine/paracrine mechanisms. Osteocytes, bone lining cells, osteomacs, and
      vascular endothelial cells also regulate bone remodelling in the BMU via cell
      signalling networks of ligand-receptor complexes. In addition, through secreted
      and membrane-bound factors in the bone microenvironment, T and B lymphocytes
      mediate bone homeostasis in osteoimmunology. CONCLUSIONS: Osteoporosis and other
      bone diseases occur because multicellular communication within the BMU is
      disrupted. Understanding the cellular and molecular basis of bone remodelling and
      the discovery of novel paracrine or coupling factors, such as RANKL, sclerostin,
      EGFL6 and semaphorin 4D, will lay the foundation for drug development against
      bone diseases.

PMID- 22465239
TI  - Too close to home. Factors predicting meat avoidance.
AB  - In most societies, meat is valued more highly, yet tabooed more frequently, than
      any other type of food. Past research suggests that people avoid eating animals
      they consider similar to themselves, but what specific factors influence which
      they eat, and which they avoid? Across an array of samples from the USA, Canada,
      Hong Kong, and India, perceived animal intelligence and appearance emerged as the
      chief predictors of disgust at the thought of eating them. Furthermore,
      reflecting on animals' psychological attributes increased reported disgust,
      especially among Euro-Canadians and Euro-Americans, suggesting that these factors
      are more influential in shaping disgust in individualistic cultural contexts.
      Concordant with past research, disgust was a major predictor of willingness to
      eat animals, but social influence (frequency of consumption by friends and
      family) also emerged as a strong predictor, especially among Hong Kong Chinese
      and Indians, providing evidence that one's friends and family have a stronger
      influence on one's food choices in collectivistic cultural contexts.

PMID- 22465241
TI  - Impact of strut height on offloading capacity of removable cast walkers.
AB  - BACKGROUND: Reducing weight-bearing stress to diabetic foot ulcers is critical to
      healing and commonly called offloading. Removable cast walkers are frequently
      used for offloading; however, patient compliance is often poor. Walkers commonly
      extend to the knee. Patients complain about walkers' weight and diminished
      balance with their use. This study compared the offloading capacity of walkers
      that varied by height. Heights included: knee, ankle, and shoe levels. To ensure
      a fair comparison the outsole and insole were standardized across the devices.
      METHODS: Eleven diabetic subjects with moderate to high risk of ulceration were
      recruited. Subjects completed four 20 m walking trials. Subjects performed one
      trial with each walker and one trial with an athletic shoe. Primary outcomes
      focused on plantar loading and were measured by pressure insoles. Secondary
      outcomes were associated with gait kinematics as collected by body worn sensors.
      FINDINGS: Significant differences were found for the peak pressure and pressure
      time integrals of the different footwear. All walkers performed better than the
      athletic shoe. The ankle and knee-high devices performed best. Center of mass
      rotation data showed a trend of the ankle walker yielding a smaller range of
      motion (18% medial/lateral and 22% anterior/posterior) than the knee level.
      INTERPRETATION: The ankle-high walker was able to provide similar offloading
      capacities as the knee-high walker. The diminished weight, along with potentially
      improved stability, may result in improved compliance with ankle-high walkers. A
      study comparing the use of the two devices for treating ulcers is now suggested.

PMID- 22465242
TI  - Biomechanical evaluation of two intramedullary nailing techniques with different
      locking options in a three-part fracture proximal humerus model.
AB  - BACKGROUND: Osteosynthesis of unstable proximal humerus fractures still remains
      challenging. The aim of this study was to investigate two intramedullary nailing
      techniques with different locking options in a three-part fracture model and
      prove whether two new fixation concepts, introducing additional locking screw-in
      screws inserted through the head of the proximal screws, and a calcar screw,
      provide better stability. METHODS: A biomechanical testing model for three-part
      proximal humerus fractures including cyclic axial loading with increasing peak
      load and simultaneous pulling forces at the rotator cuff was used to test 12
      pairs of human cadaver humeri, assigned to four groups and instrumented with
      either Targon PH (T1) or MultiLoc PHN in 3 different configurations (standard M1;
      two additional screw-in-screw M2; one additional calcar screw and two screw-in
      screw M3). FINDINGS: Initial range of motion in internal-external rotation and
      mediolateral translation was smallest in M3 (1.82 degrees ; 0.11mm), biggest in
      T1 (3.63 degrees ; 0.51mm) and significantly different between these two groups
      (p=0.02 and p=0.04, respectively). M3 showed minimum head migration along the
      nail and varus tilting after 5000 cycles (0.31mm; 0.20 degrees ) and 10000 cycles
      (1.59mm; 0.34 degrees ). M2 and M3 performed better than M1 and T1 regarding
      varus collapse. The highest number of cycles to failure was observed for M3
      (20733) and the lowest for T1 (10083) with significant difference between these
      two groups (p=0.04). INTERPRETATION: The configuration with two screw-in-screw
      and a calcar screw was superior in most aspects. The screw-in-screws were found
      to contribute against varus collapse. Both new fixation concepts could provide
      better stability in proximal humerus fractures.

PMID- 22465243
TI  - Rapid assessment of antiviral activity and cytotoxicity of silver nanoparticles
      using a novel application of the tetrazolium-based colorimetric assay.
AB  - This study centers on the development of a new screening tool for simultaneously
      evaluating the antiviral and cytotoxic properties of antiviral agents against an
      HIV-1-based, pseudotyped virus particle engineered to encode antibiotic
      resistance. The traditional colony-forming-unit assay for quantifying this type
      of virus was impractical as a screening tool due to the cumbersome nature of the
      setup and high costs in labor and supplies. Therefore, a smaller-scale and higher
      throughput means of scoring antiviral activity was successfully developed and
      used to evaluate a specific batch of 25-nm silver nanoparticles (AgNPs). The new
      assay employed a unique application of the traditional cell
      proliferation/cytotoxicity test that is based on the chemical 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, which produces a
      colorimetric readout. The AgNPs showed a half maximal inhibitory concentration
      against the virus of 11.2+/-0.6 MUg/ml (p<0.0001) with no significant toxicity
      against the cells. Because the virus was engineered to undergo only the first
      half of its replication cycle, the observed AgNP inhibition must have occurred at
      one of the early stages of infection. Overall, the new assay was very efficient
      and will be useful for testing different viral pseudotypes, screening different
      types of nanomaterials, and investigating other antiviral agents.

PMID- 22465244
TI  - The effect of galectin-3 genetic variants on the susceptibility and prognosis of
      gliomas in a Chinese population.
AB  - The aim of this study is to explore the association between the polymorphisms of
      galectin-3 gene and clinico-pathological characteristics and prognosis of
      gliomas. We enrolled 190 histologically diagnosed gliomas and 210 healthy
      controls in this study. Two genetic variants at galectin-3 single nucleotide
      polymorphism (SNP) sites (galectin-3 +191 A>C and +292 A>C) were determined. We
      found that the A/A genotype at galectin-3 gene +292 A>C was significantly more
      prevalent in gliomas patient than in controls (42.1% vs. 29.0%, P=0.021); the A
      allele frequency was markedly higher in gliomas subjects than in controls (61.8%
      vs. 45.0%, P=0.008). There was a markedly higher prevalence of AA carriers in
      high-grade subgroup than in low-grade subgroup (50.5% vs. 31.8%, P=0.012). The
      Kaplan-Meier analyses showed that the gliomas patients carrying AA genotype of
      galectin-3 gene +292 A>C had marked shorter overall survival period than those
      did not (AA vs. AC+CC, 22.2+/-3.8 months vs. 38.3 months+/-7.9; P=0.04). The SNPs
      at +191 A>C of galectin-3 gene did not show positive association with clinico
      pathological characteristics and prognosis of gliomas. The results of this study
      suggest the SNPs at +292 A>C, not SNPs at +191 A>C, of galectin-3 gene were
      associated with the tumor grade and prognosis of gliomas.

PMID- 22465245
TI  - Height-dependent difference in the expression of naloxone-induced withdrawal
      jumping behavior in morphine dependent rats.
AB  - Opiate withdrawal syndrome may motivate opiate seeking and taking. Thus,
      development of an effective medical treatment for these symptoms is a primary
      research goal and strongly relies on improved experimental models. Opiate
      withdrawal syndrome is characterized by several behavioral signs such as wet dog
      shake, teeth chattering, sniffing, scratching, chewing, diarrhea, rearing, ptosis
      and jumping. The goal of present study was to evaluate the impact of the
      cylindrical chamber height on the expression of jumping behavior in morphine
      dependent rats. Adult male Wistar rats were rendered dependent on morphine by
      subcutaneous (s.c.) injection of morphine sulfate (10 mg/kg) with an interval of
      12 h for 9 days. On day 10, 2 h after morphine injection, rats were injected with
      naloxone (1 mg/kg, i.p.). Naloxone-induced jumping was monitored during a period
      of 30 min in a clear cylindrical Plexiglas test chamber with the floor covered by
      woodchip. The chambers had the same diameter (35 cm), but the heights of chambers
      were different (30, 40, 50, 60, 70 and 80 cm). Incidence and frequency of jumping
      decreased with increasing the height of the test chambers (P<0.05). Altogether,
      these findings highlight the possibility of detecting height-dependent difference
      in the expression of naloxone-induced jumping behavior in morphine dependent
      rats.

PMID- 22465246
TI  - Angiotensin II induces protein overexpression of hyperpolarization-activated
      cyclic nucleotide-gated channels in primary cultured nodose neurons.
AB  - Modulating ion channel function includes acutely affecting the kinetics of the
      ion channels and chronically changing the expression of ion channels. Our
      previous study showed that angiotensin II (Ang II) acutely increased
      hyperpolarization-activated cyclic nucleotide-gated (HCN) currents in nodose
      ganglion (NG) neurons via NADPH oxidase-superoxide signaling. Therefore, the
      present study was to measure chronic treatment with Ang II on protein expression
      of the HCN channels in the primary cultured rat NG neurons. Immunofluorescent
      staining data showed that HCN1 was expressed in the A-type NG neurons, and HCN2
      was expressed in the C-type NG neurons. Chronic treatment of Ang II (100 nM, 12
      h) induced the protein expression of HCN2 besides the overexpression of HCN1 in
      the A-type NG neurons; and the overexpression of HCN2 in the C-type NG neurons.
      An Ang II type I receptor antagonist (1 MUM losartan), a NADPH oxidase inhibitor
      (100 MUM apocynin), or a superoxide dismutase mimetic (1mM tempol) attenuated the
      effect of Ang II to increase the protein expression of the HCN channels in rat
      nodose neurons. Whole cell patch-clamp data further confirmed that chronic
      treatment of Ang II (100 nM, 12 h) significantly enhanced the density of HCN
      currents in A- and C-type NG neurons. Above three inhibitors significantly
      inhibited the Ang II-induced increase of the HCN channel density in rat NG
      neurons. These findings suggest that Ang II-NADPH oxidase-superoxide signaling
      chronically regulates the protein expression of the HCN channels in rat nodose
      neurons.

PMID- 22465247
TI  - Direction-dependent effects of chronic "jet-lag" on hippocampal neurogenesis.
AB  - Disruptions in circadian rhythms, as seen in human shift workers, are often
      associated with many health consequences including impairments in cognitive
      functions. However, the mechanisms underlying these affects are not well
      understood. The objective of the present study is to explore the effects of
      circadian disruption on hippocampal neurogenesis, which has been implicated in
      learning and memory and could serve as a potential pathway mediating the
      cognitive consequences associated with rhythm disruption. Circadian rhythm
      disruptions were introduced using a weekly 6 h phase shifting paradigm, in which
      male Wistar rats were subjected to either 6 h phase advances (i.e. traveling
      eastbound from New York to Paris) or 6 h phase delays (i.e. traveling westbound
      from Paris to New York) in their light/dark schedule every week. The effects of
      chronic phase shifts on hippocampal neurogenesis were assessed using doublecortin
      (DCX), a microtubule binding protein expressed in immature neurons. The results
      revealed that chronic disruption in circadian rhythms inhibits hippocampal
      neurogenesis, and the degree of reduction in neurogenesis depends upon the
      direction and duration of the shifts. In two cohorts of animals that experienced
      phase shifts for either 4 or 8 weeks, a greater decrease in neurogenesis was
      observed when the phase was advanced versus delayed in both groups. The direction
      dependent effect mirrors the findings on clock gene expression in the SCN,
      suggesting a causal link between the reduction in hippocampal neurogenesis and a
      disrupted SCN circadian clock.

PMID- 22465248
TI  - Assessment of the otolith-ocular reflex using ocular vestibular evoked myogenic
      potentials in patients with episodic lateral tilt sensation.
AB  - The otolith-ocular reflex in patients with episodic lateral tilt sensation
      without any other vestibular symptoms was assessed using ocular vestibular evoked
      myogenic potentials (oVEMP). Ten patients (6 men and 4 women, mean age=53.5) were
      enrolled. All patients had episodic lateral tilt sensation. Patients with a
      medical history of rotatory vertigo, loss of consciousness, head trauma, or
      symptoms or signs of central nervous dysfunction or proprioceptive dysfunction
      and those who had been definitely diagnosed with a disease that causes
      disequilibrium were excluded. All of the 10 patients had oVEMP tests and cervical
      VEMP (cVEMP) tests and underwent caloric tests. Eight of the 10 patients showed
      unilateral absence of oVEMP, one displayed a bilateral absence, and one displayed
      normal oVEMP. Concerning cVEMP, 4 patients showed a unilateral absence of cVEMP,
      one displayed unilaterally decreased responses and 5 displayed normal cVEMP. All
      patients showed normal bilateral caloric responses. The present study showed that
      patients with episodic lateral tilt sensation displayed abnormal otolith-ocular
      reflexes, as shown by their oVEMP, suggesting that these patients were suffering
      from utricular dysfunction.

PMID- 22465249
TI  - Electroconvulsive stimulations prevent chronic stress-induced increases in L-type
      calcium channel mRNAs in the hippocampus and basolateral amygdala.
AB  - Although affective disorders have high prevalence, morbidity and mortality, we do
      not fully understand disease etiopathology, nor have we determined the exact
      mechanisms by which treatment works. Recent research indicates that intracellular
      calcium ion dysfunction might be involved. Here we use the chronic restraint
      stress model of affective disorder (6 h restraint per day for 21 days) in
      combination with electroconvulsive stimulations to examine the effects of stress
      and an effective antidepressive treatment modality on L-type voltage gated
      calcium channel subunit mRNA expression patterns in the brain. We find that
      stress tended to upregulate Ca(v)1.2 and Ca(v)1.3 channels in a brain region
      specific manner, while ECS tended to normalise this effect. This was more
      pronounced for Ca(v)1.2 channels, where stress clearly increased expression in
      both the basolateral amygdala, dentate gyrus and CA3, while stress only
      upregulated Ca(v)1.3 channel expression significantly in the dentate gyrus. ECS
      effects on Ca(v)1.2 channel expression were generally specific to stressed
      animals. Our findings are consistent with and extent previous studies on the
      involvement of intracellular calcium ion dysfunction in affective disorders.
      Selective modulation of neuronal L-type voltage gated calcium channels appears to
      be a promising target for the development of novel antidepressive treatment
      modalities.

PMID- 22465250
TI  - Pre-treatment with high doses of cocaine decreases the reinforcing effects of
      cocaine in the conditioned place preference paradigm.
AB  - The aim of the present study was to determine if pre-exposure to high doses of
      cocaine can subsequently alter the rewarding effects of this drug. Adult male
      mice received a pretreatment of physiological saline, or 12.5 or 25 mg/kg of
      cocaine (one injection a day for five days). After an interval of six days
      without injections, the rewarding effects of low doses of cocaine (0.5, 1 or 1.5
      mg/kg) were evaluated in the conditioned place preference (CPP) paradigm. Doses
      of 1 and 1.5 mg/kg induced a clear CPP in animals pre-treated with saline but
      were ineffective in those pre-treated with 25 mg/kg of cocaine. Only the dose of
      1.5 mg/kg induced CPP in mice pre-treated with 12.5 mg/kg of cocaine. Our
      results, which reveal a decrease in the conditioned rewarding effects of
      threshold doses of cocaine, demonstrate that exposure to high doses of this drug
      can alter the reward system.

PMID- 22465251
TI  - It's special the way you say it: an ERP investigation on the temporal dynamics of
      two types of prosody.
AB  - Sentence prosody is long known to serve both linguistic functions (e.g. to
      differentiate between questions and statements) and emotional functions (e.g. to
      detect the emotional state of a speaker). These different functions of prosodic
      information need to be encoded rapidly during sentence comprehension to ensure
      successful speech communication. However, systematic investigations of the
      comparative nature of these two functions, i.e. are the two functions of prosody
      independent or interdependent, are sparse. The question at hand is whether the
      two prosodic functions engage a similar neural network and run a similar time
      course or not. To this aim we investigated whether emotional and linguistic
      prosody are processed independently or dependently in an event-related brain
      potential (ERP) experiment. We merged a prosodically neutral head of a sentence
      to a second half of a sentence that differed in emotional and/or linguistic
      prosody. In a within-subjects design, two tasks were administered: in the
      "emotion task", participants judged whether the sentence that they had just heard
      was spoken in a neutral tone of voice or not (emotional task); in the "linguistic
      task", participants decided whether the sentence was a declarative sentence or
      not. As predicted, the previously reported prosodic expectancy positivity (PEP)
      was elicited by linguistic and emotional prosodic expectancy violations. However,
      the latency and distribution of the ERP component differed: whilst responses to
      emotional prosodic expectancy violations were elicited shortly after an
      expectancy violation (~470 ms post splicing-point) and most prominently at
      posterior electrode-sites, the positivity in response to linguistic prosody had a
      later onset (~620 ms post splicing-point) with a more frontal distribution.
      Interestingly, responses to combined (linguistic and emotional) expectancy
      violations resulted in a broadly distributed positivity with an onset of ~170 ms
      post expectancy violation. These effects were found irrespective of the task
      setting. Given the differences in latency and distribution, we conclude that the
      processing of emotional and linguistic prosody relies at least partly on
      differing neural mechanisms and that emotional prosodic aspects of language are
      processed in a prioritized processing stream.

PMID- 22465252
TI  - A rapid, automated approach for quantitation of rotavirus and reovirus
      infectivity.
AB  - Current microscopy-based approaches for immunofluorescence detection of viral
      infectivity are time consuming and labor intensive and can yield variable results
      subject to observer bias. To circumvent these problems, we developed a rapid and
      automated infrared immunofluorescence imager-based infectivity assay for both
      rotavirus and reovirus that can be used to quantify viral infectivity and
      infectivity inhibition. For rotavirus, monolayers of MA104 cells were infected
      with simian strain SA-11 or SA-11 preincubated with rotavirus-specific human IgA.
      For reovirus, monolayers of either HeLa S3 cells or L929 cells were infected with
      strains type 1 Lang (T1L), type 3 Dearing (T3D), or either virus preincubated
      with a serotype-specific neutralizing monoclonal antibody (mAb). Infected cells
      were fixed and incubated with virus-specific polyclonal antiserum, followed by an
      infrared fluorescence-conjugated secondary antibody. Well-to-well variation in
      cell number was normalized using fluorescent reagents that stain fixed cells.
      Virus-infected cells were detected by scanning plates using an infrared imager,
      and results were obtained as a percent response of fluorescence intensity
      relative to a virus-specific standard. An expected dose-dependent inhibition of
      both SA-11 infectivity with rotavirus-specific human IgA and reovirus infectivity
      with T1L-specific mAb 5C6 and T3D-specific mAb 9BG5 was observed, confirming the
      utility of this assay for quantification of viral infectivity and infectivity
      blockade. The imager-based viral infectivity assay fully automates data
      collection and provides an important advance in technology for applications such
      as screening for novel modulators of viral infectivity. This basic platform can
      be adapted for use with multiple viruses and cell types.

PMID- 22465253
TI  - Fisetin and rutin as 3C protease inhibitors of enterovirus A71.
AB  - Enterovirus A71 (EV-A71) causes severe complications: encephalitis, pulmonary
      edema, and death. No effective drug has been approved for clinical use. This
      study investigated the antiviral effects of flavonoids against EV-A71. An in
      vitro inhibitor screening assay using recombinant EV-A71 3C protease (3Cpro)
      demonstrated fisetin and rutin inhibiting 3Cpro enzymatic activity in a dose
      dependent manner. Cell-based fluorescence resonance energy transfer (FRET) assay
      with an EV-A71 3Cpro cleavage motif probe also confirmed that fisetin and rutin
      inhibited the replication of EV-A71 in cells. A virus replication assay indicated
      that fisetin and rutin reduced significantly the EV-A71-induced cytopathic effect
      and viral plaque titers in RD cells culture. The IC(50) values of plaque
      reduction against EV-A71 were 85 MUM for fisetin and 110 MUM for rutin.
      Therapeutic indices (CC50/IC50 of plaque reduction assays) of fisetin and rutin
      exceeded 10. The study suggests that fisetin and rutin inhibit the replication of
      EV-A71.

PMID- 22465254
TI  - Analysis of the size of DNA packaged by the human JC virus-like particle.
AB  - Previously, it has been demonstrated that the JC virus-like particle (VLP) is
      able to package DNA in E. coli and deliver the DNA into human colon cancer cells
      for gene expression. In this study, the maximum size of DNA packaged by the VLP
      was determined further. Plasmid DNAs with various sizes were packaged by the VLP
      in E. coli. Human neuroblastoma cells were then infected with the VLPs containing
      the various sizes of DNA to allow gene expression. In addition, plasmid DNAs
      packaged in the VLPs were extracted and retransformed back into E. coli under
      selection to determine the size of the DNA packaged. The results showed that the
      JC VLP was able to package plasmid DNA in E. coli up to at least 9.4 kbp in size
      and this size of DNA could be delivered successfully into human neuroblastoma
      cells for gene expression. The JC VLP is able to package exogenous DNA up to at
      least 9.4 kbp in size for gene transduction. These findings will help with the
      development of gene delivery systems using the JC VLP as the gene delivery
      vector.

PMID- 22465255
TI  - Performance of the Luminex xTAG Respiratory Viral Panel Fast in a clinical
      laboratory setting.
AB  - The aim of the study was to develop a real-time RT-PCR for the detection of
      enteroviruses (EVs) and rhinoviruses (RVs) and to assess the performance of the
      xTAG RVP Fast assay in comparison to a direct fluorescent assay (DFA), a real
      time RT-PCR assay for the detection of respiratory syncytial virus (RSV) and
      human metapneumovirus (hMPV), and the EV/RV RT-PCR assay developed in this study.
      The performance of the RVP Fast assay was assessed in the analysis of 373
      nasopharyngeal samples. For the viruses of the DFA panel, detection rates of
      27.6% and 23.8% were obtained by RVP and DFA, respectively, in analysis of a set
      of 297 samples collected in 2009-2010. These results show statistically
      significant superiority of the RVP Fast assay (P=0.049). For RSV, hMPV, EV, and
      RV, detection rates of 48.0% and 45.2% were achieved by RVP and RT-PCR,
      respectively. For individual targets, increased detection of EV/RV (P=0.043) and
      decreased detection of influenza A virus (P=0.004) by RVP in comparison to real
      time RT-PCR was observed. The results of the present study imply the need to
      adjust the InfA component of the RVP Fast assay to also cover the InfA(H1N1) 2009
      virus.

PMID- 22465257
TI  - Psoriasis: a skin disease associated with increased cardiovascular risk.
AB  - Psoriasis and psoriatic arthritis are associated with increased risk of
      cardiovascular events and cardiovascular mortality. Alongside classic risk
      factors such as atherosclerosis, the severity of psoriatic skin disease also
      influences cardiovascular risk in these patients. In both cases, endothelial
      dysfunction and increased intima-media thickness in the carotid artery are
      indicators of subclinical cardiovascular disease. Active treatment of the
      psoriasis and management of traditional cardiovascular risk factors are essential
      in order to reduce cardiovascular morbidity in these patients. Clinical practice
      guidelines on the management of cardiovascular risk will define a new integrated
      approach to the care of patients with psoriasis and psoriatic arthritis.

PMID- 22465256
TI  - Healthy Moms, a randomized trial to promote and evaluate weight maintenance among
      obese pregnant women: study design and rationale.
AB  - BACKGROUND: Obesity and excessive weight gain during pregnancy are associated
      with adverse pregnancy outcomes. Observational studies suggest that minimal or no
      gestational weight gain (GWG) may minimize the risk of adverse pregnancy outcomes
      for obese women. OBJECTIVE: This report describes the design of Healthy Moms, a
      randomized trial testing a weekly, group-based, weight management intervention
      designed to help limit GWG to 3% of weight (measured at the time of
      randomization) among obese pregnant women (BMI>=30 kg/m(2)). Participants are
      randomized at 10-20 weeks gestation to either the intervention or a single
      dietary advice control condition. PRIMARY OUTCOMES: The study is powered for the
      primary outcome of total GWG, yielding a target sample size of 160 women.
      Additional secondary outcomes include weight change between randomization and one
      year postpartum and proportion of infants with birth weight>90th percentile for
      gestational age. Statistical analyses will be based on intention-to-treat.
      METHODS: Following randomization, all participants receive a 45-minute dietary
      consultation. They are encouraged to follow the Dietary Approaches to Stop
      Hypertension diet without sodium restriction. Intervention group participants
      receive an individualized calorie intake goal, a second individual counseling
      session and attend weekly group meetings until they give birth. Research staff
      assesses all participants at 34-weeks gestation and at 2-weeks and one-year
      postpartum with their infants. SUMMARY: The Healthy Moms study is testing weight
      management techniques that have been used with non-pregnant adults. We aim to
      help obese women limit GWG to improve their long-term health and the health of
      their offspring.

PMID- 22465258
TI  - [Angiosarcoma of the skin after breast cancer radiotherapy].

PMID- 22465259
TI  - [Lipedematous alopecia in a patient with scalp psoriasis].

PMID- 22465260
TI  - Hyperpigmented plaque on the foot of a Kenyan patient.

PMID- 22465262
TI  - Issues in the extinction of specific stimulus-outcome associations in Pavlovian
      conditioning.
AB  - This paper reviews a variety of studies designed to examine the effects of
      extinction upon control by specific stimulus-outcome (S-O) associations in
      Pavlovian conditioning. Studies conducted with rats in a magazine approach
      conditioning paradigm have shown that control by specific S-O associations is
      normally unaffected by extinction treatments, although other aspects of
      conditioned responding seem affected in a more enduring way. However, recent work
      suggests that extinction can undermine control by such associations if it is
      administered after the conditioned stimulus is weakly encoded. The results from
      these studies suggest that it may be important to consider multiple response
      systems in assessing the impact of extinction. Studies conducted with the flavor
      preference learning paradigm in rats also show that specific S-O associations can
      be undermined by procedures that involve presenting a flavor cue in the absence
      of its associated nutrient. These findings provide no support for the view that
      flavor preference learning necessarily entails some unique learning process that
      differs from more conventional processes. As in other situations, some of these
      effects likely involve a masking process, but the extent to which masking or true
      associative weakening occurs in extinction more generally is a topic that is not
      well understood. Finally, we present some data to suggest that extinction also
      involves conditional "occasion-setting" control by contextual cues. Special
      procedures are recommended in assessing such learning when the goal is to
      distinguish this form of learning from other more conventional mechanisms of
      extinction.

PMID- 22465263
TI  - Pavlovian biconditional discrimination learning in the C57BL/6J mouse.
AB  - Four experiments using mice examined acquisition of Pavlovian biconditional
      discriminations in which two stimulus compounds were paired with food (AX+ and
      BY+) and two were not (AY- and BX-). Temporally asynchronous compounds were
      generated by using contextual stimuli (Experiment 1) and 15-s discrete visual
      cues (Experiments 2A, 2B and 3) to disambiguate when embedded noise or tone
      stimuli would be paired with food. When food pellets followed both reinforced
      compounds, successful acquisition was obtained in Experiment 1 but not in
      Experiments 2A and 2B even though the order of trials was modeled after that used
      in Experiment 1. However, when differential outcomes followed the reinforced
      compounds in Experiment 3, acquisition was obtained with discrete cue stimulus
      compounds. The implications of these results for modulatory models of conditional
      discrimination learning in animals are discussed.

PMID- 22465264
TI  - Phrenic motor neuron degeneration compromises phrenic axonal circuitry and
      diaphragm activity in a unilateral cervical contusion model of spinal cord
      injury.
AB  - Respiratory dysfunction is the leading cause of morbidity and mortality following
      traumatic spinal cord injury (SCI). Injuries targeting mid-cervical spinal cord
      regions affect the phrenic motor neuron pool that innervates the diaphragm, the
      primary respiratory muscle of inspiration. Contusion-type injury in the cervical
      spinal cord is one of the most common forms of human SCI; however, few studies
      have evaluated mid-cervical contusion in animal models or characterized
      consequent histopathological and functional effects of degeneration of phrenic
      motor neuron-diaphragm circuitry. In an attempt to target the phrenic motor
      neuron pool, two unilateral contusion injury paradigms were tested, a single
      injury at level C4 and a double injury both at levels C3 and C4, and animals were
      followed for up to 6 weeks post-injury. Both unilateral cervical injury paradigms
      are reproducible with no mortality or need for breathing assistance, and are
      accompanied by phrenic motor neuron loss, phrenic nerve axon degeneration,
      diaphragm atrophy, denervation and subsequent partial reinnervation at the
      diaphragm neuromuscular junction, changes in spontaneous diaphragm EMG
      recordings, and reduction in phrenic nerve compound muscle action potential
      amplitude. These findings demonstrate significant and chronically persistent
      respiratory compromise following mid-cervical SCI due to phrenic motor neuron
      degeneration. These injury paradigms and accompanying analyses provide important
      tools both for understanding mechanisms of phrenic motor neuron and diaphragm
      pathology following SCI and for evaluating therapeutic strategies in clinically
      relevant cervical SCI models.

PMID- 22465265
TI  - GABA inactivation of area V4 changes receptive-field properties of V2 neurons in
      Cebus monkeys.
AB  - To investigate the contribution of feedback circuits from area V4 to the
      receptive-field properties of V2 neurons, we used tungsten microelectrodes to
      record extracellular single units in these visual areas, before and after
      pressure injections of a solution of 0.25 mol/L of GABA in two anesthetized and
      paralyzed Cebus apella monkeys. The visual stimulus consisted of a single bar
      moving in one of eight directions. Using a device made of four stainless steel
      pipettes and one central tungsten electrode, we inactivated, with different
      amounts of GABA, topographically corresponding areas of V4, while studying V2
      neurons. We studied a total of 36 V2 neurons during six sessions of GABA
      injections into area V4. GABA inactivation of visual area V4 produced a general
      decrease in the excitability of the neurons, which included a decrease in
      spontaneous and driven activities, followed by changes in direction selectivity.
      The changes in selectivity were toward an increase in directional selectivity and
      decrease in orientation selectivity. Thus, feedback connections arising from V4,
      an area of the ventral steams of visual information processing, are capable of
      not only modulating the spontaneous and driven activity of V2 neurons, but also
      of modifying V2 receptive field properties, such as its direction and/or
      orientation selectivity.

PMID- 22465266
TI  - Studying cellular and subcellular dynamics in the developing zebrafish nervous
      system.
AB  - Cells of the developing nervous system undergo incredible proliferation, migrate
      long distances, and differentiate morphologically into highly specialized
      structures. The dynamic changes happening at the cellular and subcellular levels
      can only be properly understood using time-lapse in vivo imaging approaches, for
      which the transparent embryonic zebrafish is ideally suited. Moreover, the
      genetic techniques adapted for zebrafish provide incredible spatial, temporal,
      and quantitative control over the expression of fluorescent proteins, such that
      practically any structure or cell of interest can be highlighted. Recent
      zebrafish studies provide new insights into the dynamic nature of cell division,
      neuronal migration and axon and dendrite formation, but form only the beginning
      of a promising new era of in vivo live imaging.

PMID- 22465267
TI  - Associations between dietary cadmium exposure and bone mineral density and risk
      of osteoporosis and fractures among women.
AB  - Osteoporosis and its main health outcome, fragility fractures, are large and
      escalating public health problems. Cadmium, a widespread food contaminant, is a
      proposed risk factor; still the association between estimated dietary cadmium
      exposure and bone mineral density (BMD) has never been assessed. Within a sub
      cohort of the Swedish Mammography Cohort, we assessed dietary cadmium exposure
      based on a food frequency questionnaire (1997) and urinary cadmium (2004-2008) in
      relation to total-body BMD and risk of osteoporosis and fractures (1997-2009)
      among 2676 women (aged 56-69 years). In multivariable-adjusted linear regression,
      dietary cadmium was inversely associated with BMD at the total body and lumbar
      spine. After further adjustment for dietary factors important for bone health and
      cadmium bioavailability--calcium, magnesium, iron and fiber, the associations
      became more pronounced. A 32% increased risk of osteoporosis (95% CI: 2-71%) and
      31% increased risk for any first incident fracture (95% CI: 2-69%) were observed
      comparing high dietary cadmium exposure (>=13 MUg/day, median) with lower
      exposures (<13 MUg/day). By combining high dietary with high urinary cadmium
      (>=0.50 MUg/g creatinine), odds ratios among never-smokers were 2.65 (95% CI:
      1.43-4.91) for osteoporosis and 3.05 (95% CI: 1.66-5.59) for fractures. In
      conclusion, even low-level cadmium exposure from food is associated with low BMD
      and an increased risk of osteoporosis and fractures. The partial masking of the
      associations by essential nutrients indicates important interplay between dietary
      factors and contaminants present in food. In separate analyses, dietary and
      urinary cadmium underestimated the association with bone effects.

PMID- 22465268
TI  - Five years of anti-resorptive activity after a single dose of zoledronate-
      results from a randomized double-blind placebo-controlled trial.
AB  - Intravenous zoledronate 5 mg, administered annually, prevents fractures in people
      with osteoporosis, but the optimal dosing schedule is not known. Previously, we
      reported that a single dose of 5 mg zoledronate stably decreased bone turnover
      and increased bone mineral density (BMD) for 3 years in a randomized controlled
      trial in 50 postmenopausal women with osteopenia. We have now completed a 2-year
      double-blind extension of this trial, during which no additional treatment was
      administered. The primary endpoint was change in the bone turnover markers
      procollagen type-I N-terminal propeptide (P1NP) and beta-C-terminal telopeptide
      of type I collagen (beta-CTX); the secondary endpoint was change in BMD at lumbar
      spine, total hip and total body. Mean levels of the each of the bone turnover
      markers were lower in the zoledronate group throughout the study (P<0.0001 for
      each marker). After 5 years, mean (95% CI) levels of beta-CTX and P1NP were 277
      ng/L (150, 404) and 28 MUg/L (16, 40) lower in the zoledronate group,
      corresponding to reductions of 48% and 45%, respectively. BMD was higher in the
      zoledronate group during the study (P<0.0001 for each site). After 5 years, BMD
      in the zoledronate group was higher by 4.2% (1.1, 7.2) at the lumbar spine, by
      5.3% (2.7, 7.9) at the total hip, and by 2.7% (1.1, 4.2) at the total body. These
      findings suggest that the anti-resorptive effects of a single 5 mg dose of
      zoledronate persist for at least 5 years in postmenopausal women. Trials
      assessing the anti-fracture efficacy of dosing intervals of zoledronate of up to
      5 years are justified.

PMID- 22465269
TI  - Serum myeloperoxidase activity and oxidative stress in patients with acute
      brucellosis.
AB  - OBJECTIVES: The role of infection in the pathogenesis of atherosclerosis has been
      increasingly discussed. Previous studies have suggested that increased
      myeloperoxidase activity plays an important role in the pathogenesis of
      atherosclerosis. The aim of this study was to investigate the serum
      myeloperoxidase activity and catalase activity along with lipid hydroperoxide
      (LOOH) levels in patients with acute brucellosis. DESIGN AND METHODS: Thirty-two
      patients with brucellosis and 33 healthy controls were enrolled. Serum
      myeloperoxidase activity, catalase activity and LOOH levels were determined.
      RESULTS: Serum myeloperoxidase activity and LOOH levels were significantly higher
      in patients with brucellosis than controls (p<0.05, p<0.001), while catalase
      activity were significantly lower (p<0.001). LOOH levels were found to be
      significantly positively correlated with MPO activity (r=0.297, p=0.016) in
      patients. CONCLUSIONS: These results indicate that increased myeloperoxidase
      activity and decreased catalase activity is associated with increased oxidative
      stress, which may have a role in atherosclerotic processes in brucellosis
      patients.

PMID- 22465270
TI  - Awakening salivary cortisol levels of children with sleep bruxism.
AB  - The study of factors potentially associated with sleep bruxism (SB) may
      contribute to a better understanding of its nature and etiology. OBJECTIVES: In
      this way, this cross-sectional study aimed to evaluate the association between SB
      and salivary cortisol levels, heart rate, and other parafunctional habits. DESIGN
      AND METHODS: Data were collected in 100 healthy caries-free children of both
      genders, aged 7.23 +/- 0.60 years, with (n=27) and without (n=73) signs and
      symptoms of SB by interview with the parents and clinical and physical
      examination. Salivary cortisol was measured immediately after waking up and 30min
      after awakening for the determination of the area under the response curve
      (AURC). Data were analyzed by descriptive statistics, normality test, and
      Spearman correlation test; a stepwise logistic regression model was used to
      verify the association between SB, as the dependent variable, and age, gender,
      body mass index (BMI), heart rate, presence of sucking habit, nail biting,
      enuresis, and AURC (alpha=0.05). RESULTS: AURC did not correlate with BMI and
      heart rate. Only AURC showed a significant negative association with SB, while
      age, gender, BMI, heart rate and other parafunctional habits did not associate
      with SB. CONCLUSION: In the studied sample, children with SB were more likely to
      present low concentrations of awakening salivary cortisol.

PMID- 22465271
TI  - Identification of a novel mutation in the alpha-galactosidase A gene in patients
      with Fabry disease.
AB  - OBJECTIVES: Mutation analysis of the alpha-galactosidase A (GLA) gene is a
      valuable tool for the diagnosis of affected families. In our work, we analyze
      about one thousand samples per year from patients suspected of having Fabry
      disease (FD). DESIGN AND METHODS: We carried out high resolution melting analysis
      (HRM) and DNA sequencing of all the exons of the GLA gene. We also assayed the
      alpha-galactosidase A activity in patients' blood. RESULTS: In some members of
      one family, we identified a new mutation in the GLA gene, c.614delC. This is a
      deletion of a single nucleotide, a cytosine, in exon 4 of the gene which causes a
      frameshift mutation. CONCLUSIONS: Patients with the c.614delC mutation show
      classical clinical manifestations of FD, and the male patient has no alpha
      galactosidase A activity. These data suggest that c.614delC is a novel mutation
      associated with FD.

PMID- 22465272
TI  - Transcutaneous bilirubin measurement: comparison of Respironics BiliCheck and JM
      103 in a normal newborn population.
AB  - OBJECTIVES: To compare the accuracy of BiliCheckTM (Respironics, Marietta, GA)
      and Konica-Minolta Air Shield JM-103 (Drager Medical Inc, Telford, PA) to
      evaluate total serum bilirubin (TSB). METHODS: Prospective blinded study
      comparing two diagnostic devices in 630 neonates requiring TSB measurement.
      RESULTS: Linear regression analysis showed a good correlation between BiliCheckTM
      and TSB (r=0.8212) as well as between JM-103 and TSB (r=0.8686). BiliCheck shows
      a tendency to underestimate TSB. The mean difference in TSB-TcB was -1.4 mg/dL
      for BC (-4.7/+1.8 mg/dL) and 0.3 mg/dL for JM-103 (-2.6/+3.2mg/dL). ROC analysis
      for TSB>= 12 mg/dL showed area under the curve for BiliCheckTM significantly
      lower than those for JM-103 (p<0.0001). JM-103 resulted less time expensive than
      BiliCheck. CONCLUSIONS: In spite of similar diagnostic accuracy JM-103 could be
      preferred for some practical advantages, but its suitability in performing
      universal screening for severe hyperbilirubinemia deserves further
      investigations.

PMID- 22465273
TI  - Stability of 1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) in human
      serum.

PMID- 22465274
TI  - Performance evaluation of the Helena V8 capillary electrophoresis system.
AB  - OBJECTIVES: To compare the performance characteristics of the Helena V8(r) and
      Sebia CAPILLARYS2(r) automated capillary electrophoresis systems to agarose gel
      serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE)
      using the Helena SPIFE3000(r). DESIGN AND METHODS: Serum protein electrophoresis
      and immunosubtraction was performed on 100 consecutive patient samples comparing
      two capillary-electrophoresis platforms with agarose-gel SPE and IFE; IFE was
      used as the gold standard. Chart review was performed on patients where results
      were discordant between methods. Analytical precision was determined using
      Sebia's normal and abnormal controls. RESULTS: The sensitivities of the
      CAPILLARYS2, V8, and SPIFE3000 agarose gel for identification of monoclonal
      gammopathies were respectively 97.4 (95%CI 91.1-100), 92.3 (95%CI 82.2-100), and
      89.9 (95%CI 79.1-97.6). The specificities of the CAPILLARYS2, V8, and SPIFE3000
      agarose gel were respectively 57.6 (95%CI 45.0-70.2), 72.2 (95%CI 61.0-83.3), and
      75.4 (95%CI 60-82.8). These analytical performance characteristics were
      statistically equivalent between systems (P>0.05). The analytical precision of
      the capillary-based methods was also statistically equivalent. Chart review of
      available data from discordant samples revealed that 7/10 patients had a history
      of multiple myeloma or known monoclonal gammopathy and were being treated or
      monitored. All discordant samples had low concentration monoclonal proteins
      (<0.3g/dL). Both capillary-based methods performed poorly (collectively <50%
      accuracy) at detecting low concentration non-IgG antibodies (IgA, IgM, and light
      chain monoclonal gammopathies) compared to IFE. CONCLUSIONS: The Helena V8 and
      Sebia CAPILLARYS2 were analytically equivalent to the SIFE3000 for identification
      of IgG monoclonal gammopathies >0.3g/dL. Interpreters using the automated
      immunotyping/immunosubstraction systems performed poorly at detecting low
      concentration and non-IgG monoclonal gammopathies.

PMID- 22465275
TI  - Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in
      patients with biopsy-proven nonalcoholic fatty liver disease.
AB  - OBJECTIVES: We sought to determine whether serum concentrations of fibroblast
      growth factor 19 (FGF19) - an ileum-derived enterokine which plays a role in the
      control of glucose and lipid homeostasis - are altered in patients with biopsy
      proven nonalcoholic fatty liver disease (NAFLD). DESIGN AND METHODS: Serum levels
      of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients
      with biopsy-proven NAFLD and 74 controls. RESULTS: FGF19 levels were
      significantly lower in patients with biopsy-proven NAFLD (median: 130pg/mL) than
      in controls (median: 210pg/mL, P<0.001). Serum FGF19 levels were significantly
      but modestly associated with hepatocyte ballooning scores in univariate analysis
      (r=-0.25, P<0.05) but not after adjustment for potential confounders (beta=-0.18;
      t=1.78, P=0.08). CONCLUSIONS: This pilot study suggests that serum FGF19 levels
      are decreased in patients with NAFLD but are not independently associated with
      liver histology findings.

PMID- 22465276
TI  - Multiresidue determination of veterinary drugs in aquaculture fish samples by
      ultra high performance liquid chromatography coupled to tandem mass spectrometry.
AB  - A simple, selective and fast multiresidue method was developed for the
      determination of 32 veterinary drug residues belonging to several families, in
      gilthead sea bream (Sparus aurata) by ultra high performance liquid
      chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The extraction
      was based on modified QuEChERS (quick, easy, cheap, effective, rugged and safe)
      procedure, using as extraction solution a mixture of acetonitrile and methanol
      (75:25, v/v), and it reduces sample handling, increasing sample throughput in
      relation to current methodologies. The developed method was validated and mean
      recovery ranged from 69% to 125% (at 10, 25, 50 and 100 MUg/kg). Intra and
      interday precision, estimated as the same levels and expressed as relative
      standard deviation, RSD, were lower than 20% and 30%, respectively. Limits of
      detection (LODs) and quantification (LOQs) were lower than 7.5 and 25 MUg/kg,
      respectively, except for danofloxacin, oxytetracycline and tetracycline (LOD and
      LOQ of 15.0 and 50 MUg/kg, respectively). Decision limit (CC(alpha)) and
      detection capability (CC(beta)) were also calculated and ranged from 16.7 MUg/kg
      (levamisole) to 605.0 (flumequine) MUg/kg and from 23.5 MUg/kg (levamisole) to
      611.5 MUg/kg (flumequine), respectively. The expanded uncertainty, U, was also
      evaluated ant it was below 25% at 100 MUg/kg level, except for tetracycline
      (28%). Finally, the method was applied to ten samples obtained from local
      supermarkets in Almeria (Spain) and traces of some compounds were detected.

PMID- 22465277
TI  - Simultaneous determination and pharmacokinetics of protein unbound aspirin and
      salicylic acid in rat blood and brain by microdialysis: an application to herbal
      drug interaction.
AB  - Aspirin is commonly used for the prevention of myocardial infarction and ischemic
      stroke; whereas the Chinese people employ the bu-yang-huan-wu-tang (BYHWT) as a
      routine herbal formulation for the treatment and prevention of transient ischemic
      stroke. The current study develops a microdialysis technique coupled to a
      validated liquid chromatography system to measure free-form aspirin and salicylic
      acid for herbal-drug interaction in rat blood and brain. The intra- and inter-day
      precisions in biological dialysates were within 0.1-9.4% in the concentration
      ranges of 0.1-50 MUg/mL and the accuracies ranged from -4.7 to 6.1%. The
      pharmacokinetic data demonstrate that the area under the concentration time curve
      (AUC) of the aspirin was 2031 +/- 266 min MUg/mL after aspirin administration
      (100mg/kg, i.v.). The AUC of salicylic acid was 12660 +/- 1799 min MUg/mL, which
      suggests that aspirin is quickly hydrolyzed to salicylic acid in blood and the
      metabolite can also be detected within 15 min in brain dialysate. The herbal-drug
      pharmacokinetic interaction showed no significant effect in blood and brain. The
      results of pharmacodynamics for the bleeding time suggested that there were no
      significant differences between the aspirin alone group and the BYHWT pretreated
      group. However, the bleeding time has been prolonged when compared aspirin alone
      or the group pretreated with BYHWT to the blank control. The conclusion provides
      practical information for clinical practice for the herbal formulation BYHWT and
      aspirin used concurrently.

PMID- 22465278
TI  - A FRET-based screening assay for nucleic acid ligands.
AB  - Some of the most serious diseases are characterized by the presence of a specific
      secondary structure within DNA or RNA, often in the promoter or the coding region
      of the responsible gene, that enhances or disrupts expression of the protein.
      Structural elements that impact cellular function may also be formed in other
      genomic regions such as telomeres. Compounds that interact with such structural
      elements may be useful in diagnosis or treatment of patients. In this report, we
      present a FRET melting assay that allows testing of libraries of compounds
      against four different nucleic acid structures. Compounds are tested to determine
      whether they stabilize preformed secondary structures (i.e., whether they cause
      an increase in melting temperature (T(m))). This property is described by the
      DeltaT(m) parameter, which is the difference between the T(m) of the compound
      stabilized structure and the T(m) of the unbound structure. Model
      oligonucleotides are labeled with FAM as a fluorescent donor and TAMRA as an
      acceptor. The intensity of FAM fluorescence is recorded as a function of
      temperature. Melting temperatures are determined by the FRET method in 96-well
      plates; this assay could easily be converted into 384-well format.

PMID- 22465279
TI  - Genome-wide localization of replication factors.
AB  - Chromatin Immunoprecipitation (ChIP) is a powerful tool for the identification
      and characterization of protein-DNA interactions in vivo. ChIP has been utilized
      to study diverse nuclear processes such as transcription regulation, chromatin
      modification, DNA recombination and DNA replication at specific loci and, more
      recently, across the entire genome. Advances in genomic approaches, and whole
      genome sequencing in particular, have made it possible and affordable to
      comprehensively identify specific protein binding sites throughout the genomes of
      higher eukaryotes. The dynamic nature of the DNA replication program and the
      transient occupancy of many replication factors throughout the cell cycle present
      additional challenges that may not pertain to the mapping of site specific
      transcription factors. Here we discuss the specific considerations that need to
      be addressed in the application of ChIP to the genome-wide location analysis of
      protein factors involved in DNA replication.

PMID- 22465280
TI  - One-dimensional acoustic standing waves in rectangular channels for flow
      cytometry.
AB  - Flow cytometry has become a powerful analytical tool for applications ranging
      from blood diagnostics to high throughput screening of molecular assemblies on
      microsphere arrays. However, instrument size, expense, throughput, and consumable
      use limit its use in resource poor areas of the world, as a component in
      environmental monitoring, and for detection of very rare cell populations. For
      these reasons, new technologies to improve the size and cost-to-performance ratio
      of flow cytometry are required. One such technology is the use of acoustic
      standing waves that efficiently concentrate cells and particles to the center of
      flow channels for analysis. The simplest form of this method uses one-dimensional
      acoustic standing waves to focus particles in rectangular channels. We have
      developed one-dimensional acoustic focusing flow channels that can be fabricated
      in simple capillary devices or easily microfabricated using photolithography and
      deep reactive ion etching. Image and video analysis demonstrates that these
      channels precisely focus single flowing streams of particles and cells for
      traditional flow cytometry analysis. Additionally, use of standing waves with
      increasing harmonics and in parallel microfabricated channels is shown to
      effectively create many parallel focused streams. Furthermore, we present the
      fabrication of an inexpensive optical platform for flow cytometry in rectangular
      channels and use of the system to provide precise analysis. The simplicity and
      low-cost of the acoustic focusing devices developed here promise to be effective
      for flow cytometers that have reduced size, cost, and consumable use. Finally,
      the straightforward path to parallel flow streams using one-dimensional multinode
      acoustic focusing, indicates that simple acoustic focusing in rectangular
      channels may also have a prominent role in high-throughput flow cytometry.

PMID- 22465281
TI  - A novel peptidomics approach to detect markers of Alzheimer's disease in
      cerebrospinal fluid.
AB  - Sensitive and specific diagnosis and monitoring of disease progression are of
      prime importance to develop new therapies for Alzheimer's disease patients.
      Although the diagnostic accuracy, verified by pathological examination is high,
      it is currently not possible to diagnose Alzheimer's disease with a high degree
      of certainty until relatively late in the disease process. Here, we have
      undertaken a peptidome analysis of postmortem cerebrospinal fluid of
      neuropathologically confirmed Alzheimer's disease patients and non-demented
      controls using a combination of methods and technologies. This includes novel
      sample preparation based on the enrichment of endogenous, proteolytically derived
      peptides as well as peptides non-covalently bound to abundant proteins. We
      observed differences in peptide profiles associated with Alzheimer's disease in
      the endogenous peptide fraction and in the protein-bound peptide fraction. The
      discriminating peptides in the unbound peptide fraction were identified as VGF
      nerve growth factor inducible precursor, and complement C4 precursor, whereas the
      discriminating peptides in the protein-bound fraction were identified as VGF
      nerve growth factor inducible precursor, and alpha-2-HS-glycoprotein.

PMID- 22465282
TI  - 2D gels and their third-dimension potential.
AB  - Two-dimensional (2D) agarose gel electrophoresis is one of the most powerful
      methods to analyze the mass and shape of replication intermediates. It is often
      use to map replication origins but it is also useful to characterize termination
      of replication, replication fork barriers and even replication fork reversal.
      Here, we present protocols, figures and movies with a thorough description of
      different modes of replication for linear DNA fragments and the corresponding
      patterns they generate in 2D gels.

PMID- 22465283
TI  - Challenges in multi-plex and mono-plex platforms for the discovery of
      inflammatory profiles in neurodegenerative diseases.
AB  - Pro and anti-inflammatory cytokines are involved in disease onset and
      pathophysiology of multiple sclerosis, Alzheimer's disease and Parkinson's
      disease. It is likely that panels of multiple cytokines provide a good reflection
      of disease status and can be used as biological markers in body fluids. Different
      multi-plex platforms, Luminex-xMAP and Meso Scale Discovery, are able to detect
      multiple analytes in the same sample at the same time. In this literature based
      review, we offer an overview of the multi-plex platforms and compare them with
      the golden standard ELISA in their ability to accurately and sensitively detect
      cytokines in cerebrospinal fluid (CSF) and blood (serum/plasma). The
      detectability and levels of cytokines in multiple sclerosis, Alzheimer's disease
      and Parkinson's disease are promising but also show discrepancies between
      studies. The current immuno-assays lack sensitivity for detection of various
      cytokines that have low concentrations of cytokines in CSF and blood, and
      therefore technical improvements are needed. With such improvements the use of
      large panels of cytokines as inflammatory profiles may offer additional value in
      diagnosis, prognosis and therapeutic response in neurodegenerative diseases.

PMID- 22465284
TI  - Mass spectrometry and ion mobility spectrometry of G-quadruplexes. A study of
      solvent effects on dimer formation and structural transitions in the telomeric
      DNA sequence d(TAGGGTTAGGGT).
AB  - We survey here state of the art mass spectrometry methodologies for investigating
      G-quadruplexes, and will illustrate them with a new study on a simple model
      system: the dimeric G-quadruplex of the 12-mer telomeric DNA sequence
      d(TAGGGTTAGGGT), which can adopt either a parallel or an antiparallel structure.
      We will discuss the solution conditions compatible with electrospray ionisation,
      the quantification of complexes using ESI-MS, the interpretation of ammonium ion
      preservation in the complexes in the gas phase, and the use of ion mobility
      spectrometry to resolve ambiguities regarding the strand stoichiometry, or
      separate and characterise different structural isomers. We also describe that
      adding electrospray-compatible organic co-solvents (methanol, ethanol,
      isopropanol or acetonitrile) to aqueous ammonium acetate increases the stability
      and rate of formation of dimeric G-quadruplexes, and causes structural
      transitions to parallel structures. Structural changes were probed by circular
      dichroism and ion mobility spectrometry, and the excellent correlation between
      the two techniques validates the use of ion mobility to investigate G-quadruplex
      folding. We also demonstrate that parallel G-quadruplex structures are easier to
      preserve in the gas phase than antiparallel structures.

PMID- 22465285
TI  - [Infectious mononucleosis and severe thrombocytopenia].
AB  - Infectious mononucleosis by Epstein-Barr virus is usually a benign self-limiting
      disease. We present two cases admitted in the same week, with suspected co
      infection by other viruses (cytomegalovirus and human herpes virus 6), which
      showed severe thrombocytopenia in the acute phase of the disease. The progress
      and treatment were different in each case.

PMID- 22465286
TI  - [Knowledge, attitudes and asthma quality of life of adolescents in schools. The
      need to educate our teaching centres].
AB  - INTRODUCTION: Knowledge and attitudes toward asthma can condition the integration
      of adolescents with asthma in school and affect their quality of life. Our
      objective was to determine the state of knowledge, attitudes on asthma in
      secondary schools, and its relationship to quality of life of pupils with asthma,
      as an early step to an educational intervention. METHODS: Descriptive and cross
      sectional study of pupils aged 13 and 14 years old and their teachers in 26
      schools of Seville and province. We used, as study tools, the Newcastle Asthma
      Knowledge Questionnaire, the Gibson attitudes towards asthma, and the Paediatric
      Asthma Quality of Life Questionnaire. To assess the normality of variables, the
      Kolmogorov-Smirnov test was used, and for non-parametric variables the U Mann
      Whitney and W Wilcoxon tests were used. For the association between variables, we
      use the regression coefficients and rho Spearman. RESULTS: We studied 3827 pupils
      (279 with asthma) and 548 teachers. All had little knowledge about asthma. The
      quality of life in asthma was mild to moderately affected, and lower in girls,
      5.38+/-1.08 (95% CI=5.20 to 5.55) than in boys 5.77 (+/- 1.18) (95% CI=5.56 to
      5.97), P=.0000. We found no relationship between knowledge, attitudes and quality
      of life in asthma. CONCLUSIONS: We found a low level of knowledge about asthma in
      pupils and teacher. Asthma sufferers have a mild to moderate asthma quality of
      life, which is worse for girls. Knowledge has no relationship with attitudes to
      asthma in all groups, or with the quality of life of asthma sufferers.

PMID- 22465287
TI  - Developmental pathways linking externalizing symptoms, internalizing symptoms,
      and academic competence to adolescent substance use.
AB  - This study extends previous research investigating the developmental pathways
      predicting adolescent alcohol and marijuana use by examining the cascading
      effects of externalizing and internalizing symptoms and academic competence in
      the prediction of use and level of use of these substances in adolescence.
      Participants (N=191) were drawn from a longitudinal study of first-born children
      of low-income mothers. Using data from ages 7, 9, 12, and 16 years, a series of
      nested two-part (semi-continuous) path models from a developmental cascade
      modeling framework were compared. Controlling for gender, SES, mother's age at
      child's birth, and minority status, we found (a) within-domain rank-order
      stability across time, (b) significant cross-domain effects over time, (c) higher
      externalizing symptoms significantly predicted use of alcohol and marijuana as
      well as higher levels of use in adolescence, and (d) higher levels of academic
      competence significantly added to the prediction of use of alcohol.

PMID- 22465288
TI  - Developing healthcare rule-based expert systems: case study of a heart failure
      telemonitoring system.
AB  - BACKGROUND: The use of expert systems to generate automated alerts and patient
      instructions based on telemonitoring data could enable increased self-care and
      improve clinical management. However, of great importance is the development of
      the rule set to ensure safe and clinically relevant alerts and instructions are
      sent. The purpose of this work was to develop a rule-based expert system for a
      heart failure mobile phone-based telemonitoring system, to evaluate the expert
      system, and to generalize the lessons learned from the development process for
      use in other healthcare applications. METHODS: Semi-structured interviews were
      conducted with 10 heart failure clinicians to inform the development of a draft
      heart failure rule set for alerts and patient instructions. The draft rule set
      was validated and refined with 9 additional interviews with heart failure
      clinicians. Finally, the clinical champion of the project vetted the rule set.
      The concerns voiced by the clinicians during the interviews were noted, and
      methods to mitigate these concerns were employed. The rule set was then evaluated
      as part of a 6-month randomized controlled trial of a mobile phone-based heart
      failure telemonitoring system (n=50 for each of the telemonitoring and control
      groups). RESULTS: The developed expert system generated alerts and instructions
      based on the patient's weight, blood pressure, heart rate, and symptoms. During
      the trial, 1620 alerts were generated, which led to various clinical actions
      including 105 medication changes/instructions. The findings from the trial
      indicated the rule set was associated with improved quality of life and self
      care. CONCLUSIONS: A rule set was developed with extensive input by heart failure
      clinicians. The results from the trial indicated the rule set was associated with
      significantly increased self-care and improved the clinical management of heart
      failure. The developed rule set can be used as a basis for other heart failure
      telemonitoring systems, but should be validated and modified as necessary. In
      addition, the process used to develop the rule set can be generalized and applied
      to create robust and complete rule sets for other healthcare expert systems.

PMID- 22465289
TI  - Insights into the completely annotated genome of Lactobacillus buchneri CD034, a
      strain isolated from stable grass silage.
AB  - Lactobacillus buchneri belongs to the group of heterofermentative lactic acid
      bacteria and is a common member of the silage microbiome. Here we report the
      completely annotated genomic sequence of L. buchneri CD034, a strain isolated
      from stable grass silage. The whole genome of L. buchneri CD034 was sequenced on
      the Roche Genome Sequencer FLX platform. It was found to consist of four
      replicons, a circular chromosome, and three plasmids. The circular chromosome was
      predicted to encode 2319 proteins and contains a genomic island and two prophages
      which significantly differ in G+C-content from the remaining chromosome. It
      possesses all genes for enzymes of a complete phosphoketolase pathway, whereas
      two enzymes necessary for glycolysis are lacking. This confirms the
      classification of L. buchneri CD034 as an obligate heterofermentative lactic acid
      bacterium. A set of genes considered to be involved in the lactate degradation
      pathway and genes putatively involved in the breakdown of plant cell wall
      polymers were identified. Moreover, several genes encoding putative S-layer
      proteins and two CRISPR systems, belonging to the subclasses I-E and II-A, are
      located on the chromosome. The largest plasmid pCD034-3 was predicted to encode
      57 genes, including a putative polysaccharide synthesis gene cluster, whereas the
      functions of the two smaller plasmids, pCD034-1 and pCD034-2, remain cryptic.
      Phylogenetic analysis based on sequence comparison of the conserved marker gene
      rpoA reveals that L. buchneri CD034 is more closely related to Lactobacillus
      hilgardii strains than to Lactobacillus brevis and Lactobacillus plantarum
      strains. Comparison of the L. buchneri CD034 core genome to other fully sequenced
      and closely related members of the genus Lactobacillus disclosed a high degree of
      conservation between L. buchneri CD034 and the recently sequenced L. buchneri
      strain NRRL B-30929 and a more distant relationship to L. buchneri ATCC 11577 and
      L. brevis ssp. gravesensis ATCC 27305, which cluster together with L. hilgardii
      type strain ATCC 8290. L. buchneri CD034 genome information will certainly
      provide the basis for further postgenome studies with the objective to optimize
      application of the strain in silage production.

PMID- 22465290
TI  - Establishment of a microcarrier culture system with serial sub-cultivation for
      functionally active human endothelial cells.
AB  - A microcarrier culture system was established for a large-scale production of
      functional human endothelial cells. It has been difficult to cultivate human
      endothelial cells in large quantities for the reasons that specific growth factor
      and extracellular matrix are required for the survival and proliferation of the
      cells and the life span of the primary cells are limited. A lot of studies have
      reported that the shear stress gives significant influences on the structure,
      growth rate and biological functions of endothelial cells. We aimed to develop a
      convenient microcarrier culture system for human endothelial cells which can
      reproduce the flow effects experienced in vivo or in vitro. In 200 mL volume
      culture, human umbilical vein endothelial cells (HUVEC) could be serially sub
      cultivated by optimizing the culture conditions such as shear strength, growth
      factor, beads and seeding cell concentration, serum concentration, and passage
      timing. The growth rate was enhanced depending on the shear strength and the life
      span of the cells was elongated until over 43PDL which is much longer than those
      of monolayer cultures. The cells maintained the diploidy of over 80% without
      obvious abnormal changes in the chromosomes. The serially sub-cultured
      microcarrier cells maintained various endothelial cell functions such as the
      syntheses of von Willebrand factor (vWf), prostacyclin and other biological
      substances, the expression of CD31, and the VEGF(165) dependent growth
      characteristic. The synthesis of biological products was affected by shear
      strength. In the case of prostacyclin, a different synthesis response was
      observed between steady flow and transiently reduced shear strength. The
      synthesis of endothelin-1 (ET-1) was down-regulated by increase of shear strength
      different from those of other products. The culture system was scaled up until 2
      L volume under the optimum DO control. The cells synthesized IL-6 in response to
      shear strength. These results indicate that the established microcarrier system
      might be able to contribute to the supply of functional human endothelial cells
      for various medical applications such as the reconstruction of injured blood
      vessels caused by atherosclerosis or restenosis of coronary arteries after
      angioplasty, and the construction of an anti-coagulable artificial blood vessel
      or an artificial skin with good transplant-ability.

PMID- 22465291
TI  - A simplified method for constructing artificial microRNAs based on the osa-MIR528
      precursor.
AB  - Artificial miRNAs (amiRNAs) have been used successfully in various plants to
      silence endogenous genes or viral RNAs. The method of Schwab et al., widely used
      to construct amiRNAs, requires four PCRs. We describe a simplified method of
      constructing amiRNA based on the osa-MIR528 backbone using one PCR step by
      addition of prolonging sequence to the primers. The length of prolonging sequence
      needed in the osa-MIR528 precursor was determined. Using this method, we
      constructed amiRNA targeting the Nicotiana benthamiana UPF1 gene and showed that
      it functioned in silencing UPF1 expression in leaves when expressed transiently.

PMID- 22465292
TI  - Enzyme catalysis in organic solvents: influence of water content, solvent
      composition and temperature on Candida rugosa lipase catalyzed
      transesterification.
AB  - In the present study the influence of water content, solvent composition and
      reaction temperature on the transesterification of 1-phenylpropan-2-ol catalyzed
      by Candida rugosa lipase was examined. Reactions were carried out in different
      mixtures of hexane and tetrahydrofurane. The studies showed that an increasing
      water content of the organic solvent results in an increasing enzyme activity and
      a decreasing enantiomeric excess. Furthermore, a significant influence of the
      solvent hydrophilicity both on the enzyme activity and on the enantiomeric excess
      was found. An increase in solvent hydrophilicity leads to a decrease of enzyme
      activity and an increase of the enantiomeric excess. This indicates that the
      enzyme becomes more selective with decreasing flexibility. Similar effects were
      found by variation of the reaction temperature. Taken together, the decrease in
      conversion and the increase in selectivity with increasing solvent hydrophilicity
      are induced by the different water contents on the enzyme surface and not by the
      solvent itself.

PMID- 22465293
TI  - Metabolite fingerprinting of barley whole seeds, endosperms, and embryos during
      industrial malting.
AB  - Samples of whole seeds, isolated endosperms including the aleurone layer and
      isolated embryos with attached scutellum from an industrial scale barley malting
      process (variety Braemar) were analysed for their water soluble metabolites by
      gas chromatography-mass spectrometry (GC-MS). 73 known metabolites and about 350
      unknown signals were detected. Principal component analysis (PCA) showed a time
      dependent shift of sample profiles. Whole seeds and endosperm samples showed very
      similar patterns with nearly all compounds rising until the end of germination.
      In the embryos a maximum concentration of compounds was reached after 72-96 h of
      malting. Most concentrations decreased afterwards. The kilning step, namely the
      drying and roasting of germinated seeds, induced variable effects of increases,
      stability or decreases of metabolites and thereby separated kilned samples from
      germinated seeds in the PCA. A second barley cultivar (Quench) underwent the same
      malting and analysis procedures and gave nearly identical results. Fructose,
      malate, myo-inositol and raffinose exhibited the potential to serve as markers
      for specific developmental stages of seeds in both varieties. Biological markers
      represent targets for industrial process control. Their potential application
      would meet the maltsters' demand to flatten variances in germination properties
      and to produce equal composed malt by directed malting management.

PMID- 22465294
TI  - Fragmented and delayed electrograms within fibrofatty scar predict arrhythmic
      events in arrhythmogenic right ventricular cardiomyopathy: results from a
      prospective risk stratification study.
AB  - BACKGROUND: Islets of myocytes within fibrofatty scars represent the substrate
      for reentrant ventricular arrhythmias in arrhythmogenic right ventricular
      cardiomyopathy (ARVC). Electroanatomic mapping can reliably identify such areas.
      OBJECTIVE: To prospectively test the association between late and fragmented
      electrograms within scar and arrhythmic events in patients with ARVC. METHODS:
      High-density right ventricle electroanatomic mapping was performed in 32 patients
      with ARVC without history of cardiac arrest or sustained ventricular arrhythmias.
      Standard definitions of electroanatomic scars and fragmented, isolated, and very
      late potentials were used. All patients received an implantable cardioverter
      defibrillator for the primary prevention of sudden death. RESULTS: After a mean
      follow-up of 25 +/- 7 months, 12 (38%) patients received appropriate implantable
      cardioverter-defibrillator shock for sustained ventricular arrhythmias. With the
      exception of a higher rate of previous syncope (P = .053), patients with
      arrhythmic events at follow-up did not differ from those who remained free from
      arrhythmic events in terms of other clinical variables, including cardiac
      magnetic resonance findings. Electroanatomic scars were present in all patients.
      The distribution and extent of electroanatomic scars were similar in the 2 groups
      (38 +/- 25 cm(2) vs 33 +/- 20 cm(2); P = .51). However, patients with implantable
      cardioverter-defibrillator shock had a higher prevalence of fragmented
      electrograms (92% vs 20%; P <.001), of isolated late potentials (75% vs 20%; P =
      .004), and of very late potentials (67% vs 25%; P = .030). Fragmented
      electrograms were the only variable independently associated with arrhythmic
      events at follow-up (hazard ratio 21; P = .015). CONCLUSION: The presence of
      fragmented and delayed electrograms within the scar predicts arrhythmic events in
      ARVC.

PMID- 22465295
TI  - Correlation between substrate location and ablation strategy in patients with
      ventricular tachycardia late after myocardial infarction.
AB  - BACKGROUND: The requirement for epicardial radiofrequency ablation (RFA) is still
      undefined in ventricular tachycardia (VT) late after myocardial infarction (MI).
      OBJECTIVE: The purpose of this study was to evaluate the correlation between the
      need for epicardial RFA and the clinical and electrophysiologic characteristics
      of VT late after MI. METHODS: Endocardial mapping and RFA were performed for VT
      late after MI, followed by epicardial mapping and RFA if no endocardial substrate
      was present or endocardial RFA failed. RESULTS: Seventy patients with VT late
      after MI (30 anterior MI [A-MI] and 40 posteroinferior MI [PI-MI]) were included
      in the study. Forty-one VTs in patients with A-MI and 64 VTs in patients with PI
      MI were targeted for RFA. Epicardial mapping and ablation were attempted in 6
      patients and performed successfully in only 4 patients. All 6 (100%) patients
      requiring epicardial access had PI-MIs. Patients with epicardial RFA had
      endocardial low-voltage areas of smaller size compared to patients without
      epicardial RFA (21 +/- 13 cm(2) vs 68 +/- 40 cm(2); P <.01). During 25 +/- 19
      months of follow-up, recurrence after the initial procedure was noted in 12 of 30
      patients (40%) with A-MI and in 18 of 40 patients (45%) with PI-MI. There was no
      significant difference between groups. CONCLUSION: In the majority of patients,
      clinical and slower VTs late after MI can be abolished using endocardial RFA.
      Rarely indicated, epicardial RFA is more commonly required in patients with small
      sized PI-MI. During follow-up, VT recurrence after successful RFA is common.

PMID- 22465296
TI  - Bryostatin analogue-induced apoptosis in mantle cell lymphoma cell lines.
AB  - The anti-cancer effects of bryostatin-1, a potent diacylglycerol analogue, have
      traditionally been attributed to its action on protein kinase C. However, we
      previously documented apoptosis in a B non-Hodgkin lymphoma cell line involving
      diacylglycerol analogue stimulation of Ras guanyl-releasing protein, a Ras
      activator, and Bim, a proapoptotic Bcl-2 family protein. To further explore the
      role of Bim, we examined several Bim-deficient B non-Hodgkin lymphoma cells for
      their responses to pico, a synthetic bryostatin-1-like compound. The Bim(-)
      mantle cell lymphoma cell lines Jeko-1, Mino, Sp53, UPN1, and Z138 and the Bim(+)
      cell line Rec-1, as well as the Burkitt lymphoma cells lines BL2 (Bim(-)) and
      Daudi (Bim(+)), were examined for their response to pico using assays for
      proliferation and apoptosis as well as biochemical methods for Ras guanyl
      releasing proteins and Bcl-2 family members. With the exception of UPN1, mantle
      cell lymphoma cell lines underwent pico-induced apoptosis, as did BL2. In some
      cases, hallmarks of apoptosis were substantially diminished in the presence of
      mitogen-activated protein kinase kinase inhibitors. Pico treatment generally led
      to increased expression of proapoptotic Bik, although the absolute levels of Bik
      varied considerably between cell lines. A pico-resistant variant of Z138
      exhibited decreased Bik induction compared to parental Z138 cells. Pico also
      generally decreased expression of anti-apoptotic Bcl-XL and Mcl1. Although, these
      changes in Bcl-2 family members seem unlikely to fully account for the
      differential behavior of the cell lines, our demonstration of a potent apoptotic
      process in most cell lines derived from mantle cell lymphoma encourages a re
      examination of diacylglycerol analogues in the treatment of this subset of B non
      Hodgkin lymphoma cases.

PMID- 22465298
TI  - Functional activation of the cerebral cortex related to sensorimotor adaptation
      of reactive and voluntary saccades.
AB  - Potentially dangerous events in the environment evoke automatic ocular responses,
      called reactive saccades. Adaptation processes, which maintain saccade accuracy
      against various events (e.g. growth, aging, neuro-muscular lesions), are to date
      mostly relayed to cerebellar activity. Here we demonstrate that adaptation of
      reactive saccades also involves cerebral cortical areas. Moreover, we provide the
      first identification of the neural substrates of adaptation of voluntary
      saccades, representing the complement to reactive saccades for the active
      exploration of our environment. An fMRI approach was designed to isolate
      adaptation from saccade production: an adaptation condition in which the visual
      target stepped backward 50 ms after saccade termination was compared to a control
      condition where the same target backstep occurred 500 ms after saccade
      termination. Subjects were tested for reactive and voluntary saccades in separate
      sessions. Multi-voxel pattern analyses of fMRI data from previously-defined
      regions of interests (ROIs) significantly discriminated between adaptation and
      control conditions for several ROIs. Some of these areas were revealed for
      adaptation of both saccade categories (cerebellum, frontal cortex), whereas
      others were specifically related to reactive saccades (temporo-parietal junction,
      hMT+/V5) or to voluntary saccades (medial and posterior areas of intra-parietal
      sulcus). These findings critically extend our knowledge on brain motor plasticity
      by showing that saccadic adaptation relies on a hitherto unknown contribution of
      the cerebral cortex.

PMID- 22465299
TI  - A crossmodal crossover: opposite effects of visual and auditory perceptual load
      on steady-state evoked potentials to irrelevant visual stimuli.
AB  - Mechanisms of attention are required to prioritise goal-relevant sensory events
      under conditions of stimulus competition. According to the perceptual load model
      of attention, the extent to which task-irrelevant inputs are processed is
      determined by the relative demands of discriminating the target: the more
      perceptually demanding the target task, the less unattended stimuli will be
      processed. Although much evidence supports the perceptual load model for
      competing stimuli within a single sensory modality, the effects of perceptual
      load in one modality on distractor processing in another is less clear. Here we
      used steady-state evoked potentials (SSEPs) to measure neural responses to
      irrelevant visual checkerboard stimuli while participants performed either a
      visual or auditory task that varied in perceptual load. Consistent with
      perceptual load theory, increasing visual task load suppressed SSEPs to the
      ignored visual checkerboards. In contrast, increasing auditory task load enhanced
      SSEPs to the ignored visual checkerboards. This enhanced neural response to
      irrelevant visual stimuli under auditory load suggests that exhausting capacity
      within one modality selectively compromises inhibitory processes required for
      filtering stimuli in another.

PMID- 22465297
TI  - Measuring and manipulating brain connectivity with resting state functional
      connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic
      stimulation (TMS).
AB  - Both resting state functional magnetic resonance imaging (fcMRI) and transcranial
      magnetic stimulation (TMS) are increasingly popular techniques that can be used
      to non-invasively measure brain connectivity in human subjects. TMS shows
      additional promise as a method to manipulate brain connectivity. In this review
      we discuss how these two complimentary tools can be combined to optimally study
      brain connectivity and manipulate distributed brain networks. Important clinical
      applications include using resting state fcMRI to guide target selection for TMS
      and using TMS to modulate pathological network interactions identified with
      resting state fcMRI. The combination of TMS and resting state fcMRI has the
      potential to accelerate the translation of both techniques into the clinical
      realm and promises a new approach to the diagnosis and treatment of neurological
      and psychiatric diseases that demonstrate network pathology.

PMID- 22465300
TI  - Inhibition of Japanese encephalitis virus entry into the cells by the envelope
      glycoprotein domain III (EDIII) and the loop3 peptide derived from EDIII.
AB  - Japanese encephalitis virus (JEV) infection is a major cause of acute viral
      encephalitis both in humans and animals. The domain III of virus envelope protein
      (EDIII) plays important roles in interacting with host cell receptors to
      facilitate virus entry. In this study, recombinant JEV EDIII was expressed and
      purified. The protein showed the ability to inhibit JEV infection in BHK-21 cells
      with 50% inhibition at a concentration of 25MUg/ml. Based on NMR structure of JEV
      EDIII, we chose several loop peptides that were reported to be related to
      receptor binding to test their possible inhibitory activities on virus infection.
      Our in vitro experiments demonstrated that one of the loop peptides (loop3) can
      prevent JEV infection with 50% inhibition at concentration of 10MUM by
      interfering in virus attachment to the cells. Our in vivo experiments on mice
      showed the loop3 was the most protective peptide when administered before virus
      challenge. Therefore, the loop3 peptide may be served as basis for the
      development of novel antiviral agents against Japanese encephalitis virus or
      other flaviviruses infection.

PMID- 22465301
TI  - Protective immunity against Legionnaires' disease in an A/J mouse model using a
      DNA vaccine composed of an outer membrane protein (29 kDa) and the pilE fusion
      protein.
AB  - In order to assess the protective effects of the DNA vaccine (pcDip/pilE) against
      Legionella pneumophila, the coding sequences of the 2 proteins were cloned into
      the pET32a(+) and pcDNA3.1(+) vectors. To provide an enhanced immunological
      response, the proteins were linked together. In this study, the A/J mouse model
      was used for examine the immunogenicity and protective efficacy of the DNA
      vaccines of pcDip, pcDpilE and pcDip/pilE. Our results showed that the total IgG
      titers were higher level increasing after the stimulation of pcDip/pilE than
      pcDip and pcDpilE immunization. The DNA vaccine (pcDip/pilE) can protect the A/J
      mouse against a higher dose (2 * 10(7)L. pneumophila cells) of L. pneumonia
      compared to the other single-DNA vaccine in our study, and the ratio of the
      survival reached 100% in 10 days after the last DNA vaccine immunization. Our
      study indicates that these findings provide experimental evidence to support the
      claim that pcDip/pilE may be an efficient DNA vaccine against Legionella
      pneumophila.

PMID- 22465302
TI  - Opportunities for improved trauma care of the elderly - a single center analysis
      of 2090 severely injured patients.
AB  - PURPOSE: Western trauma centers are increasingly confronted with elderly trauma
      patients in parallel to an increase of the elderly population. The purpose of
      this study was to identify shortcomings and opportunities for improvement in the
      treatment of elderly trauma patients. MATERIALS AND METHODS: Retrospective
      analysis of a prospectively collected single-center trauma database. Patients
      were grouped according to age and analyzed using univariate and multivariate
      analysis. RESULTS: 158 patients (7.6%) were older than 75 years, and 604 patients
      (28.9%) were between 50 and 75 years. Although comparable with respect to injury
      severity (injury severity score (ISS) 29-33) and age-adjusted Acute Physiologic
      and Chronic Health Evaluation (APACHE) score, there was a significant increase in
      mortality beyond the age of 50 (>75 years: 63.9%), with age being an independent
      predictor of mortality. Despite a similar rate and severity of head injuries
      (affecting 71% of all patients), mortality of head injuries was highest in
      patients >75 years (70.2%), accounting for the increased mortality in this group.
      Patients >75 years old were less likely to undergo craniotomy, and withdrawal of
      medical support occurred five times more frequently. Surviving patients >=50
      years required shorter ICU care than patients below 50 years (7.8 vs. 12.4 days).
      CONCLUSIONS: With increasing life expectancy and sustained independence, elderly
      trauma patients have become a regular occurrence in trauma services. Despite
      comparable injury severity and physiologic status upon admission, these patients
      suffer from disproportionately high mortality rates. Closed head injuries account
      for the majority of fatalities, regardless of the extent of therapeutic measures
      applied.

PMID- 22465303
TI  - Oxytocin, attachment, betrayal and self-interest: A commentary on "Oxytocin
      modulates the link between adult attachment and cooperation through reduced
      betrayal aversion" by Carsten K.W. De Dreu, Psychoneuroendocrinology,
      doi:10.1016/j.psyneuen.2011.10.003.

PMID- 22465304
TI  - Comparative study of iron oxide nanoparticles as-prepared and dispersed in
      Copaiba oil using Mossbauer spectroscopy with low and high velocity resolution.
AB  - Iron oxide nanoparticles, probably magnetite, as-prepared and dispersed in
      Copaiba oil were studied by Mossbauer spectroscopy using two different
      spectrometers: with a low velocity resolution (512 channels) for measurements at
      295 and 21K and with a high velocity resolution (4096 channels) for measurements
      at 295 and 90K. The fitting of all measured spectra demonstrated that usual
      models applied to fit Mossbauer spectra of magnetite and maghemite particles were
      not suitable. Therefore, the recorded spectra were fitted using a large number of
      spectral components on the basis of better quality of the fit and linearity of
      differential spectra. The number of components obtained for the better fit
      appeared to be different for spectra measured with a low and a high velocity
      resolution. However, these results demonstrated differences of Mossbauer
      parameters for iron oxide nanoparticles as-prepared and dispersed in Copaiba oil
      at applied temperatures. The effect of Copaiba oil molecules on Mossbauer
      parameters may be a result of the interactions of polar molecules such as
      kaurinic acid with nanoparticles' surface.

PMID- 22465305
TI  - Comparative study of the iron cores in human liver ferritin, its pharmaceutical
      models and ferritin in chicken liver and spleen tissues using Mossbauer
      spectroscopy with a high velocity resolution.
AB  - Application of Mossbauer spectroscopy with a high velocity resolution (4096
      channels) for comparative analysis of iron cores in a human liver ferritin and
      its pharmaceutically important models Imferon, Maltofer((r)) and Ferrum Lek as
      well as in iron storage proteins in chicken liver and spleen tissues allowed to
      reveal small variations in the (57)Fe hyperfine parameters related to differences
      in the iron core structure. Moreover, it was shown that the best fit of Mossbauer
      spectra of these samples required different number of components. The latter may
      indicate that the real iron core structure is more complex than that following
      from a simple core-shell model. The effect of different living conditions and age
      on the iron core in chicken liver was also considered.

PMID- 22465306
TI  - Molecular and serological prevalence of Anaplasma marginale in cattle of North
      Central Morocco.
AB  - A cross sectional study was conducted to investigate the epidemiological
      distribution of Anaplasma marginale in North Central Morocco. Blood samples from
      five provinces of Morocco were collected from apparently healthy cattle (n=668)
      and simultaneously analyzed by a nested polymerase chain reaction (nPCR) assay
      and competitive enzyme-linked immunosorbent assay (cELISA). The overall
      prevalence of A. marginale was 21.9% by nPCR and 16.5% by cELISA. The Kappa
      coefficient between nPCR and cELISA indicated a modest level of agreement (0.54).
      The prevalence of A. marginale varied significantly according to the province and
      the month of sampling. However age, gender and breed did not have a significant
      effect on the prevalence of this pathogen. The highest prevalence of A. marginale
      was found in the Gharb, a sub-humid area while the lowest was reported in the
      Saiss, a semi-arid area. These results indicate that an A. marginale infection
      are widespread in the country and suggests that either or both techniques are
      excellent tools for epidemiological studies and control programs.

PMID- 22465307
TI  - Retinitis pigmentosa patients' attitudes toward participation in retinal
      prosthesis trials.
AB  - PURPOSE: We undertook a questionnaire study to explore the retinitis pigmentosa
      (RP) patients' attitudes and the main reasons for or against participation in
      retinal prosthesis trials. METHODS: Fifty-four patients, who might be potential
      participants of retinal prosthesis trials, were recruited to complete the
      questionnaire devised to determine RP patients' willingness, motivations and
      expectations toward participation in retinal prosthesis trials, identify the
      concerns of RP patients about participation in retinal prosthesis trials.
      RESULTS: Eleven (11/54[21%]) of fifty-four patients were willing to participate
      in retinal prosthesis trials. Nineteen patients (19/54[35%]) declined
      participation and twenty-four patients (24/54[44%]) were unsure whether to
      participate or not. The main reasons cited for willingness to participate in
      retinal prosthesis trials were high expectations for possible therapeutic
      benefits (7/11[63.6%]), altruistic desire to help others (3/11[27.3%]), getting
      better care and closer follow-up (5/11[45.5%]). Conversely, fear of potential
      risks and side effects (12/19[63.2%]), worry of efficacy of retinal prosthetic
      devices (11/19[57.9%]), poor logistical supports (8/19[42.1%]), having difficulty
      in understanding information about retinal prosthesis trials (9/19[47.4%]) were
      main reasons cited for patients who declined to participate in retinal prosthesis
      trials. CONCLUSIONS: The willingness to participate in retinal prosthesis trials
      is low in RP patients with severe visual impairment. Altruistic motivation should
      be encouraged and establishing realistic expectations should be an important
      readiness for retinal prosthesis trials. Sufficient logistical supports and
      better understanding of the proposed trial may improve the attitudes for
      participation in retinal prosthesis trials.

PMID- 22465308
TI  - The gonangulum: a reassessment of its morphology, homology, and phylogenetic
      significance.
AB  - The gonangulum is a sclerite in the female genitalic region of insects. Its
      presence or full development has long been considered an apomorphy supporting
      Zygentoma + Pterygota. Recent studies of female genitalia in several insect
      orders (K.-D. Klass and co-workers) revealed many new data on the gonangulum and
      homologous sclerotisations (laterocoxa LC9). Herein the gonangulum area is
      described (including articulations, muscle attachments, sulci) and compared among
      Archaeognatha, Zygentoma, Odonata, Dermaptera, Dictyoptera, and Notoptera. A
      wider perspective is provided to the topic by addressing some novel issues:
      identification of LC9 sclerotisations in non-insect taxa and in insects that
      secondarily lack an ovipositor; occurrence of homonomous sclerotisations in other
      abdominal segments of both sexes; morphological interpretation of LC9; and the
      role of paedomorphosis in LC9 evolution. As a result, there is currently no
      support for any insect lineage from this character system. For gonangulum-related
      characters both a significant intra-ordinal variation and frequent homoplasy are
      demonstrated using various Odonata, Dermaptera, and Dictyoptera as examples.
      Divergent fates of LC9 in simplified genitalia are shown using a dermapteran and
      an odonatan. We view all this as a showcase of how a renewed and more detailed
      examination of a character system can dramatically change the phylogenetic
      evidence drawn from it.

PMID- 22465310
TI  - Multidimensionality of behavioural phenotypes in Atlantic cod, Gadus morhua.
AB  - Much of the inter-individual variation observed in animal behaviour is now
      attributed to the existence of behavioural phenotypes or animal personalities.
      Such phenotypes may be fundamental to fisheries and aquaculture, yet there have
      been few detailed studies of this phenomenon in exploited marine animals. We
      investigated the behavioural and neuroendocrine responses of Atlantic cod (Gadus
      morhua L.), to situations reflecting critical ecological challenges: predator
      attacks and territorial challenges. Both hatchery-reared and wild fish were
      tested and behavioural profiles were compared with baseline conditions. We then
      used an objective, multivariate approach, rather than assigning individuals along
      one-dimensional behavioural axes, to examine whether distinct behavioural
      phenotypes were present. Our results indicate that two distinct behavioural
      phenotypes were evident in fish from each background. In hatchery-reared fish,
      phenotypes displayed divergent locomotor activity, sheltering, brain monoamine
      concentrations and responses to competitive challenges. In wild fish, phenotypes
      were distinguished primarily by locomotor activity, sheltering and responsiveness
      to predator stimuli. Hatcheries presumably represent a more stressful social
      environment, and social behaviour and neuroendocrine responses were important in
      discerning behavioural phenotypes in hatchery fish, whereas antipredator
      responses were important in discerning phenotypes in wild fish that have
      previously encountered predators. In both fish types, behavioural and
      physiological traits that classified individuals into phenotypes were not the
      same as those that were correlated across situations. These results highlight the
      multidimensionality of animal personalities, and that the processes that regulate
      one suite of behavioural traits may be very different to the processes that
      regulate other behaviours.

PMID- 22465309
TI  - Exendin-4 decreases amphetamine-induced locomotor activity.
AB  - Glucagon-like peptide-1 (GLP-1) is released in response to nutrient ingestion and
      is a regulator of energy metabolism and consummatory behaviors through both
      peripheral and central mechanisms. The GLP-1 receptor (GLP-1R) is widely
      distributed in the central nervous system, however little is known about how GLP
      1Rs regulate ambulatory behavior. The abused psychostimulant amphetamine (AMPH)
      promotes behavioral locomotor activity primarily by inducing the release of the
      neurotransmitter dopamine. Here, we identify the GLP-1R agonist exendin-4 (Ex-4)
      as a modulator of behavioral activation by AMPH. We report that in rats a single
      acute administration of Ex-4 decreases both basal locomotor activity as well as
      AMPH-induced locomotor activity. Ex-4 did not induce behavioral responses
      reflecting anxiety or aversion. Our findings implicate GLP-1R signaling as a
      novel modulator of psychostimulant-induced behavior and therefore a potential
      therapeutic target for psychostimulant abuse.

PMID- 22465311
TI  - Effects of different post-match recovery interventions on subsequent athlete
      hormonal state and game performance.
AB  - We tested the effects of different post-match recovery interventions on the
      subsequent hormonal responses to a physical stress-test and game performance in
      professional rugby union players. On four occasions, participants (n=12)
      completed a video session (1 h each) with accompanying coach feedback the day
      after a rugby union match. The interventions showed either video footage of
      player mistakes with negative coach feedback (NCF1) or player successes with
      positive feedback (PCF1). Both approaches were repeated (NCF2 and PCF2). In the
      following week, participants were assessed for their free testosterone (T) and
      cortisol (C) responses to a physical stress-test, pre-game T and game-ranked
      performance. The PFC1 and PCF2 approaches were both associated with significantly
      (p<0.01) greater free T (36% to 42%) responses to the stress-test when compared
      to NCF1 and NCF2 (16% to -3%), respectively. The PCF interventions were also
      associated with higher (28% to 51%) pre-game T concentrations and superior game
      ranked performances than the NCF approaches (p<0.01). In conclusion, the post
      game presentation of specific video footage combined with different coach
      feedbacks appeared to influence the free hormonal state of rugby players and game
      performance several days later. Therefore, within the sporting context, future
      behaviour and performance might be modified through the use of simple
      psychological strategies. These data are applicable to generalised human stress
      responses and their modifiability by prior exposure to a stressor.

PMID- 22465312
TI  - Cholinergic modulation of food and drug satiety and withdrawal.
AB  - Although they comprise only a small portion of the neurons in the region,
      cholinergic interneurons in the dorsal striatum appear to play an important role
      in the regulation of various appetitive behaviors, in part, through their
      interactions with mesolimbic dopamine (DA) systems. In this review, we describe
      studies that suggest that the activity of cholinergic interneurons in the nucleus
      accumbens (NAc) and cholinergic projections to the ventral tegmental area (VTA)
      affect feeding behavior. In vivo microdialysis studies in rats have revealed that
      the cessation of a meal is associated with a rise in acetylcholine (ACh) levels
      in the NAc. ACh activation will suppress feeding, and this is also associated
      with an increase in synaptic accumulation of ACh. Further, we discuss how, in
      addition to their role in the ending of a meal, cholinergic interneurons in the
      NAc play an integral role in the cessation of drug use. Another cholinergic
      system involved in different aspects of appetitive behavior is the projection
      from the pedunculpontine nuclei directly to the VTA. Activation of this system
      enhances behaviors through activation of the mesolimbic DA system, and antagonism
      of ACh receptors in the VTA can reduce drug self-administration. Finally, we
      discuss the role of accumbens ACh in both drug and palatable food withdrawal.
      Studies reveal that accumbens ACh is increased during withdrawal from several
      different drugs of abuse (including cocaine, nicotine and morphine). This rise in
      extracellular levels of ACh, coupled with a decrease in extracellular levels of
      DA, is believed to contribute to an aversive state, which can manifest as
      behaviors associated with drug withdrawal. This theory has also been applied to
      studies of overeating and/or "food addiction," and the findings suggest a similar
      imbalance in DA/ACh levels, which is associated with behavioral indications of
      drug-like withdrawal. In summary, cholinergic neurons play an important role in
      the modulation of both food and drug intake, as well as the aversive aspects of
      food- and drug-related addictive behaviors.

PMID- 22465313
TI  - Quercetin inhibits rhinovirus replication in vitro and in vivo.
AB  - Rhinovirus (RV), which is responsible for the majority of common colds, also
      causes exacerbations in patients with asthma and chronic obstructive pulmonary
      disease. So far, there are no drugs available for treatment of rhinovirus
      infection. We examined the effect of quercetin, a plant flavanol on RV infection
      in vitro and in vivo. Pretreatment of airway epithelial cells with quercetin
      decreased Akt phosphosphorylation, viral endocytosis and IL-8 responses. Addition
      of quercetin 6h after RV infection (after viral endocytosis) reduced viral load,
      IL-8 and IFN responses in airway epithelial cells. This was associated with
      decreased levels of negative and positive strand viral RNA, and RV capsid
      protein, abrogation of RV-induced eIF4GI cleavage and increased phosphorylation
      of eIF2alpha. In mice infected with RV, quercetin treatment decreased viral
      replication as well as expression of chemokines and cytokines. Quercetin
      treatment also attenuated RV-induced airway cholinergic hyperresponsiveness.
      Together, our results suggest that quercetin inhibits RV endocytosis and
      replication in airway epithelial cells at multiple stages of the RV life cycle.
      Quercetin also decreases expression of pro-inflammatory cytokines and improves
      lung function in RV-infected mice. Based on these observations, further studies
      examining the potential benefits of quercetin in the prevention and treatment of
      RV infection are warranted.

PMID- 22465314
TI  - Two distinct dysfunctions in diabetic mouse mesenteric artery contraction are
      caused by changes in the Rho A-Rho kinase signaling pathway.
AB  - Diabetic complications are associated with small artery dysfunctions. The
      objective of this study was to identify differences in endothelial cell-denuded
      mesenteric artery second branch (mesenteric artery-2) contraction, as a typical
      small artery, between diabetic and non-diabetic mice. Contractile responses in
      mesenteric artery-2 were assessed in male type 2 diabetic ob/ob mice aged 16-22
      weeks and in age-matched control (Lean) mice. Phenylephrine induced dose
      dependent contractions in Lean mice (1126.8 +/- 28.6 mN/mm tissue at 10 MUM
      phenylephrine; n=5), which were significantly reduced in ob/ob mice (716.8 +/-
      40.8 mN/mm at 10 MUM phenylephrine; n=5). Exposure to high glucose (HG; twice the
      normal glucose [NG] concentration) enhanced phenylephrine-induced contraction in
      Lean (1341.4 +/- 15.5 mN/mm; n=5) but not in ob/ob mice. These dysfunctions did
      not involve alpha(1)-receptor sensitization or protein kinase activity, although
      the calcium sensitivity of contraction was decreased in ob/ob mice. The Rho
      kinase inhibitor Y27632 suppressed the difference between Lean and ob/ob mice
      under NG conditions, which was accompanied by Rho A inactivation. Under HG
      conditions, glucose-dependent Rho A activation persisted in ob/ob mice whereas
      Rho kinase expression was reduced. These data suggest that inactivation of Rho A
      reduced contractibility under NG conditions, and the lack of glucose dependency
      is associated with reduced Rho kinase expression.

PMID- 22465315
TI  - Risk factors for peripheral arterial disease among patients with chronic kidney
      disease.
AB  - Patients with chronic kidney disease (CKD) have an increased risk for developing
      peripheral arterial disease (PAD). The aim of this study was to examine the cross
      sectional association between novel risk factors and prevalent PAD in patients
      with CKD. A total of 3,758 patients with estimated glomerular filtration rates of
      20 to 70 ml/min/1.73 m(2) who participated in the Chronic Renal Insufficiency
      Cohort (CRIC) study were included in the present analysis. PAD was defined as an
      ankle-brachial index <0.9 or a history of arm or leg revascularization. After
      adjustment for age, gender, race, cigarette smoking, physical activity, history
      of hypertension and diabetes, pulse pressure, high-density lipoprotein
      cholesterol, estimated glomerular filtration rate, and CRIC clinical sites,
      several novel risk factors were significantly associated with PAD. For example,
      odds ratios for a 1-SD higher level of risk factors were 1.18 (95% confidence
      interval [CI] 1.08 to 1.29) for log-transformed high-sensitivity C-reactive
      protein, 1.18 (95% CI 1.08 to 1.29) for white blood cell count, 1.15 (95% CI 1.05
      to 1.25) for fibrinogen, 1.13 (95% CI 1.03 to 1.24) for uric acid, 1.14 (95% CI
      1.02 to 1.26) for glycosylated hemoglobin, 1.11 (95% CI 1.00 to 1.23) for log
      transformed homeostasis model assessment of insulin resistance, and 1.35 (95% CI
      1.18 to 1.55) for cystatin C. In conclusion, these data indicate that
      inflammation, prothrombotic state, oxidative stress, insulin resistance, and
      cystatin C were associated with an increased prevalence of PAD in patients with
      CKD. Further studies are warranted to examine the causal effect of these risk
      factors on PAD in patients with CKD.

PMID- 22465316
TI  - Fate of patients with prehospital resuscitation for ST-elevation myocardial
      infarction and a high rate of early reperfusion therapy (results from the PREMIR
      [Prehospital Myocardial Infarction Registry]).
AB  - Patients with acute ST-segment elevation myocardial infarction (STEMI) needing
      prehospital cardiopulmonary resuscitation (CPR) have a very high adverse-event
      rate. However, little is known about the fate of these patients and predictors of
      mortality in the era of early reperfusion therapy. From March 2003 through
      December 2004, 2,317 patients with prehospital diagnosed STEMI were enrolled in
      the Prehospital Myocardial Infarction Registry. One hundred ninety patients
      (8.2%) underwent prehospital CPR and were included in our analysis. Overall 90%
      of patients were treated with early reperfusion therapy, 56.3% received
      prehospital thrombolysis and 1/2 of these patients received early percutaneous
      coronary intervention after thrombolysis, 28.4% of patients were treated with
      primary percutaneous coronary intervention, and 5.3% received in-hospital
      thrombolysis. Total mortality was 40.0%. The highest mortality was seen in
      patients with asystole (63%) or pulseless electric activity (64%). Independent
      predictors of mortality were need for endotracheal intubation and older age,
      whereas ventricular fibrillation as initial heart rhythm was associated with
      survival. In conclusion, in this large registry with prehospital diagnosed STEMI,
      incidence of prehospital CPR was about 8%. Even with a very high rate of early
      reperfusion therapy, in-hospital mortality was high. Especially in elderly
      patients with asystole as initial heart rhythm and with need for endotracheal
      intubation, prognosis is poor despite aggressive reperfusion therapy.

PMID- 22465317
TI  - Role of non-high-density lipoprotein cholesterol in predicting cerebrovascular
      events in patients following myocardial infarction.
AB  - Although there appears to be a role for statins in reducing cerebrovascular
      events, the exact role of different lipid fractions in the etiopathogenesis of
      cerebrovascular disease (CVD) is not well understood. A secondary analysis of
      data collected for the placebo arm (n = 2,078) of the Cholesterol and Recurrent
      Events (CARE) trial was performed. The CARE trial was a placebo-controlled trial
      aimed at testing the effect of pravastatin on patients after myocardial
      infarction. Patients with histories of CVD were excluded from the study. A Cox
      proportional-hazards model was used to evaluate the association between plausible
      risk factors (including lipid fractions) and risk for first incident CVD in
      patients after myocardial infarction. At the end of 5 years, 123 patients (6%)
      had incident CVD after myocardial infarction (76 with stroke and 47 with
      transient ischemic attack). Baseline non-high-density lipoprotein (HDL)
      cholesterol level emerged as the only significant lipid risk factor that
      predicted CVD; low-density lipoprotein cholesterol and HDL cholesterol were not
      significant. The adjusted hazard ratios (adjusted for age, gender, hypertension,
      diabetes mellitus, and smoking) for CVD were 1.28 (95% confidence interval [CI]
      1.06 to 1.53) for non-HDL cholesterol, 1.14 (95% CI 0.96 to 1.37) for low-density
      lipoprotein cholesterol, and 0.90 (95% CI 0.75 to 1.09) for HDL cholesterol (per
      unit SD change of lipid fractions). This relation held true regardless of the
      level of triglycerides. After adjustment for age and gender, the hazard ratio for
      the highest natural quartile of non-HDL was 1.76 (95% CI 1.05 to 2.54), compared
      to 1.36 (95% CI 0.89 to 1.90) for low-density lipoprotein cholesterol. In
      conclusion, non-HDL cholesterol is the strongest predictor among the lipid risk
      factors of incident CVD in patients with established coronary heart disease.

PMID- 22465318
TI  - Relation of dosing of the renin-angiotensin system inhibitors after cardiac
      resynchronization therapy to long-term prognosis.
AB  - Dosing of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor
      blockers (ARBs) in patients with heart failure (HF) treated with cardiac
      resynchronization therapy (CRT) may affect long-term outcomes. Retrospective data
      were collected at baseline and follow-up for consecutive patients who had CRT
      implanted and attended the institutional specialist HF pacing clinic. The study
      end point was death from any cause or hospitalization for worsening HF 24 months
      after implantation. Ninety-one patients (72 men, 68 +/- 12 years old) with
      decreased left ventricular ejection fraction (24 +/- 6%) were included. At
      baseline 85 patients (93%) were on ACE inhibitors/ARBs. At 6 months 3 patients
      had died and 86 of 88 (98%) were on ACE inhibitors/ARBs. Doses were uptitrated
      from 55 +/- 35% of target dose (TD) at baseline to 62 +/- 31% TD at month 6 (p =
      0.018), whereas blood pressure was unchanged. Patients treated with <50% TD of
      ACE inhibitors/ARBs (n = 20) at month 6 had worse 24-month event-free survival
      than those on 50% to 99% TD (n = 38, p = 0.011, log-rank test) or >=100% TD (n =
      30, p = 0.007, log-rank test). Failure to achieve a dose >=50% TD of ACE
      inhibitors/ARBs at 6 months after CRT implantation was an independent predictor
      of all-cause mortality or hospitalization (hazard ratio 3.99, 95% confidence
      interval 1.66 to 9.62, p = 0.002) after adjustment for potential confounders
      including age, estimated glomerular filtration rate, diabetes and New York Heart
      Association class. In conclusion optimal dosing of ACE inhibitors/ARBs is an
      independent predictor of prognosis in patients with HF treated with CRT and it
      can be achieved by a structured follow-up within a specialized HF pacing clinic.

PMID- 22465319
TI  - Long-term outcomes of heart transplantation recipients with transplant coronary
      artery disease who develop in-stent restenosis after percutaneous coronary
      intervention.
AB  - This retrospective study assessed long-term clinical outcomes of patients with
      orthotopic heart transplantation (OHT) and transplant coronary artery disease
      (TCAD) who developed in-stent restenosis (ISR) after percutaneous coronary
      intervention (PCI). TCAD is a major cause of morbidity and mortality after the
      first year after OHT. Description of outcomes in patients with ISR after
      revascularization for TCAD is limited. One hundred five patients underwent PCI
      with bare-metal stents or drug-eluting stents at the UCLA Medical Center from
      1995 throughout 2009, of whom 83 patients (79.0%) underwent repeat angiography
      for clinical symptoms or surveillance. The primary end point was the composite of
      death, myocardial infarction, or repeat OHT. ISR occurred in 26 patients (31.3%)
      who underwent follow-up angiography. Initial treatment strategies for the 26
      patients with ISR were target vessel revascularization in 19 (73.1%), repeat OHT
      in 3 (11.5%), and medical therapy in only 4 (15.4%). At 7 years freedom from the
      primary end point was lower in patients with ISR compared to patients without ISR
      (27.9% vs 63.2%, p = 0.006, log-rank test) primarily driven by a lower survival
      rate in patients with ISR (38.5% vs 84.2%, p <0.001, log-rank test). Although
      numerically smaller in patients with ISR, there were no statistically significant
      differences in freedom from myocardial infarction (80.8% vs 91.2%, log-rank p =
      0.18) and freedom from repeat OHT (73.1% vs 84%, p = 0.22, long-rank test). In
      conclusion, patients with OHT who develop ISR after PCI have poor long-term
      prognosis. Improvements in prevention and treatment of TCAD such as increased
      pharmacotherapy are needed.

PMID- 22465320
TI  - Elucidating the role of 5-HT(1A) and 5-HT(7) receptors on 8-OH-DPAT-induced
      behavioral recovery after experimental traumatic brain injury.
AB  - 8-OH-DPAT is a 5-HT(1A/7) receptor agonist that enhances behavioral recovery
      after traumatic brain injury (TBI). This study is a first attempt to decipher
      whether the benefits induced by 8-OH-DPAT after TBI are mediated by 5-HT(1A) or 5
      HT(7) receptors. A single i.p. injection of 8-OH-DPAT (0.5 mg/kg) alone or co
      administered with either the 5-HT(1A) or 5-HT(7) receptor antagonists WAY 100635
      (0.5 mg/kg) or SB 269970 HCl (2.0 mg/kg), respectively, or vehicle control (1.0
      mL/kg) was given 15 min after cortical impact or sham injury. Function was
      assessed by established motor and cognitive tests. No difference in motor
      performance was observed among the TBI groups. Spatial acquisition was enhanced,
      relative to vehicle controls, by 8-OH-DPAT alone and when co-administered with
      WAY 100635, but not when combined with SB 269970 HCl. These data imply that 5
      HT(1A) receptor antagonism does not abate the 8-OH-DPAT-induced cognitive
      benefits, but 5-HT(7) receptor antagonism does, which suggests that the 8-OH-DPAT
      induced benefits in this single administration paradigm may be mediated more by 5
      HT(7) versus 5-HT(1A) receptors. Evaluation of a specific 5-HT(7) receptor
      agonist will further elucidate the contribution of 5-HT(1A) and 5-HT(7) receptors
      on behavioral recovery conferred by acute 8-OH-DPAT treatment after TBI.

PMID- 22465321
TI  - Transient focal cerebral ischemia differentially decreases Homer1a and 1b/c
      contents in the postsynaptic density.
AB  - Homer is a scaffold protein in the postsynaptic density (PSD) and binds to the
      intracellular tail of group I metabotropic glutamate receptors (mGluRs). Although
      Homer contributes to the regulation of physiological function in synapses, the
      role of Homer proteins under pathophysiological conditions, such as cerebral
      ischemia, is still not fully clear. In the present study, we sought to determine
      whether transient focal cerebral ischemia would affect the level of Homer1 in the
      isolated-PSD fraction from rats. We showed that Homer1a (short form) and
      Homer1b/c (long form) as well as group I mGluR were localized in the cortical
      PSD. Cerebral ischemia decreased the content of Homer1a, which is a dominant
      negative inhibitor of the long form of Homer proteins, in the PSD at 4 h of
      reperfusion without changing the level of Homer1a in cortical homogenates. On the
      other hand, the levels of Homer1b/c in the both PSD and homogenates were
      decreased at 24 h of reperfusion. These results suggest that these decreases in
      the level of Homer1 proteins after cerebral ischemia may contribute to the
      disturbance of synaptic function and subsequent development of cerebral ischemia.

PMID- 22465322
TI  - Suppression of autophagy exacerbates Mefloquine-mediated cell death.
AB  - Mefloquine is an effective treatment drug for malaria. However, it can cause
      several adverse side effects, and the precise mechanism associated with the
      adverse neurological effects of Mefloquine is not clearly understood. In this
      study, we investigated the effect of Mefloquine on autophagy in neuroblastoma
      cells. Mefloquine treatment highly induced the formation of autophagosomes and
      the conversion of LC3I into LC3II. Moreover, Mefloquine-induced autophagy was
      efficiently suppressed by an autophagy inhibitor and by down regulation of ATG6.
      The autophagy was also completely blocked in ATG5 deficient mouse embryonic
      fibroblast cells. Moreover, suppression of autophagy significantly intensified
      Mefloquine-mediated cytotoxicity in SH-SY5Y cells. Our findings suggest that
      suppression of autophagy may exacerbate Mefloquine toxicity in neuroblastoma
      cells.

PMID- 22465323
TI  - Fibrin conduit supplemented with human mesenchymal stem cells and
      immunosuppressive treatment enhances regeneration after peripheral nerve injury.
AB  - To address the need for the development of bioengineered replacement of a nerve
      graft, a novel two component fibrin glue conduit was combined with human
      mesenchymal stem cells (MSC) and immunosupressive treatment with cyclosporine A.
      The effects of MSC on axonal regeneration in the conduit and reaction of
      activated macrophages were investigated using sciatic nerve injury model. A 10mm
      gap in the sciatic nerve of a rat was created and repaired either with fibrin
      glue conduit containing diluted fibrin matrix or fibrin glue conduit containing
      fibrin matrix with MSC at concentration of 80*10(6) cells/ml. Cells were labeled
      with PKH26 prior to transplantation. The animals received daily injections of
      cyclosporine A. After 3 weeks the distance of regeneration and area occupied by
      regenerating axons and ED1 positives macrophages was measured. MSC survived in
      the conduit and enhanced axonal regeneration only when transplantation was
      combined with cyclosporine A treatment. Moreover, addition of cyclosporine A to
      the conduits with transplanted MSC significantly reduced the ED1 macrophage
      reaction.

PMID- 22465324
TI  - Common and differential brain responses in men and women to nonverbal emotional
      vocalizations by the same and opposite sex.
AB  - Nonverbal emotional vocalizations are one of the most elementary ways of
      communicating in humans. We examined the impact of sex differences on neural
      responses to laughter and crying produced by the same and opposite sex. Thirty
      subjects (15 women) underwent functional magnetic resonance imaging during a sex
      identification task for laughter, crying, and neutral voices. The parahippocampal
      gyrus was involved in both men and women while hearing laughter of the same sex,
      suggesting greater positive emotional processing and greater attention toward
      emotional context in response to laughter of the same sex than of the opposite
      sex. The posterior cingulate was involved in both men and women while hearing
      crying of the opposite sex, suggesting that empathic processing may occur more in
      response to crying of the opposite sex than of the same sex. Furthermore, brain
      responses to crying of the opposite sex seem to reflect upon men's efforts to
      perform emotional regulation and women's empathic concerns.

PMID- 22465325
TI  - MiR-9 promotes the neural differentiation of mouse bone marrow mesenchymal stem
      cells via targeting zinc finger protein 521.
AB  - MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous
      triggers of the RNA interference pathway. Recent studies have shown that microRNA
      9 (miR-9) plays a regulatory role in the development and differentiation of stem
      cells and neural precursor cells. We have found that miR-9 is able to promote the
      differentiation of bone marrow mesenchymal stem cells (MSCs), but the mechanisms
      of miR-9 in this process remains poorly understood. An increasing number of
      studies have found that zinc-finger protein 521 (Zfp521) expression is high in
      most immature cells and decreases with differentiation. Zfp521 could induce
      neural conversion of embryonic stem cells. However, little is known about the
      expression of Zfp521 and its relationship with miR-9 with respect to the neural
      differentiation of MSCs. In this study, we found the expression of Zfp521
      declined with the neural differentiation of MSCs, and miR-9 could promote the
      neural differentiation via targeting Zfp521.

PMID- 22465326
TI  - Alternative splicing: decoding an expansive regulatory layer.
AB  - Alternative splicing (AS) is the process by which splice sites in precursor (pre)
      mRNA are differentially selected to produce multiple mRNA and protein isoforms.
      During the past few years the application of genome-wide profiling technologies
      coupled with bioinformatic approaches has transformed our understanding of AS
      complexity and regulation. These studies are further driving research directed at
      elucidating the functions of networks of regulated AS events in the context of
      normal physiology and disease. Major strides have also been made in understanding
      how AS is functionally integrated with- and coupled to- gene regulation at the
      level of chromatin and transcription. Particularly intriguing is the discovery of
      new AS 'switches' that control transcriptional networks required for animal
      development and behavior.

PMID- 22465327
TI  - Dengue and dengue-like outbreaks in the past: the case of the Macau epidemic
      fever of 1874.
AB  - Historical sources abound in references to outbreaks of a disease resembling
      dengue fever. Medical observers reported on its rapid onset and great expansion
      in the population, the diversity and changeability of its clinical features and
      its overall mildness. In 1874, an epidemic disease with fever, rash and rheumatic
      pains as main symptoms broke out in the Portuguese colony of Macau, South China.
      It was similar to the epidemic disease which swept the colony 2 years before
      during the socalled dengue pandemic of 1870-1873. The 1874 epidemic disease was
      variously labeled by local physicians, including dengue fever. In his report on
      the disease, Dr. Lucio Augusto da Silva, hence at the head of the health services
      of Macau, discussed on the nature of the epidemic febrile disease. Here, I review
      the data on the 1874 epidemic outbreak and put them in the context of historical
      dengue-like outbreaks. A possible Chikungunya etiology of the disease is
      postulated.

PMID- 22465329
TI  - A high-affinity monoclonal antibody against the FLAG tag useful for G-protein
      coupled receptor study.
AB  - The FLAG sequence (DYKDDDDK) is an artificial sequence widely used to detect,
      quantify, and purify proteins expressed as FLAG-fusion proteins. Several highly
      specific monoclonal antibodies for FLAG are commercially available; however, they
      are not always sensitive enough to detect proteins expressed at low levels and
      can give rise to unacceptable levels of background signal when used for
      immunostaining in vitro and in vivo. The current study reports the successful
      establishment of hybridoma cells that produce an extremely high-affinity antibody
      to FLAG, namely 2H8 Ab. 2H8 Ab stained FLAG-tagged G-protein-coupled receptors
      more strongly than commercially available antibodies in both flow cytometry and
      immunostaining experiments with no background staining. 2H8 was sensitive enough
      to detect FLAG-tagged G-protein-coupled receptors and soluble proteins in crude
      preparations, which could not be achieved using commercially available
      antibodies. Only 10 ng of 2H8 Ab was required to immunoprecipitate FLAG-tagged G
      protein-coupled receptors from cell lysates. Of note, 2H8 stained FLAG-tagged
      BLT2, a low-affinity leukotriene B4 receptor, expressed in vivo in the small
      intestine of mice under control of the villin promoter. Thus, 2H8 Ab is a
      promising tool for analyzing various FLAG-fusion proteins, particularly G-protein
      coupled receptors, both in vitro and in vivo.

PMID- 22465328
TI  - GFR at initiation of dialysis and mortality in CKD: a meta-analysis.
AB  - BACKGROUND: The proportion of patients with advanced chronic kidney disease (CKD)
      initiating dialysis therapy at a higher glomerular filtration rate (GFR) has
      increased during the past decade. Recent data suggest that higher GFR may be
      associated with increased mortality. STUDY DESIGN: A meta-analysis of cohort
      studies and trials. SETTING & POPULATION: Patients with advanced CKD. SELECTION
      CRITERIA FOR STUDIES: We performed a systematic literature search in MEDLINE,
      Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American
      Society of Nephrology abstracts, and bibliographies of retrieved articles to
      identify studies reporting on GFR at dialysis therapy initiation and mortality.
      PREDICTOR: Estimated or calculated GFR at dialysis therapy initiation. OUTCOME:
      Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality.
      RESULTS: 16 cohort studies and 1 randomized controlled trial were identified (n =
      1,081,116). By meta-analysis restricted to 15 cohorts (n = 1,079,917), higher GFR
      at dialysis therapy initiation was associated with a higher pooled adjusted HR
      for all-cause mortality (1.04; 95% CI, 1.03-1.05; P < 0.001). However, there was
      significant heterogeneity (I(2) = 97%; P < 0.001). The association persisted
      among the 9 cohorts that adjusted analytically for nutritional covariates (HR,
      1.03; 95% CI, 1.02-1.04; P < 0.001; residual I(2) = 97%). The highest mortality
      risk was observed in hemodialysis cohorts (HR, 1.05; 95% CI, 1.02-1.08; P <
      0.001), whereas there was no association between GFR and mortality in peritoneal
      dialysis cohorts (HR, 1.04; 95% CI, 0.99-1.08, P = 0.1; residual I(2) = 98%).
      Finally, higher GFR was associated with a lower mortality risk in cohorts that
      calculated GFR (HR, 0.80; 95% CI, 0.71-0.91; P = 0.003), contrasting with a
      higher mortality risk in cohorts that estimated GFR (HR, 1.04; 95% CI, 1.03-1.05;
      P < 0.001; residual I(2) = 97%). LIMITATIONS: Paucity of randomized controlled
      trials, different methods for determining GFR, and substantial heterogeneity.
      CONCLUSIONS: Higher estimated rather than calculated GFR at dialysis therapy
      initiation is associated with a higher mortality risk in patients with advanced
      CKD, independent of nutritional status. Although there was substantial
      heterogeneity of effect size estimates across studies, this observation requires
      further study.

PMID- 22465330
TI  - Application of magnetic hydroxyapatite nanoparticles for solid phase extraction
      of plasmid DNA.
AB  - We developed a facile method for plasmid DNA (pDNA) extraction from crude
      Escherichia coli lysate using magnetic hydroxyapatite nanoparticles (MHapNPs) in
      the presence of polyethylene glycol (PEG)/NaCl. DNA condensation induced by
      PEG/NaCl is a prerequisite for achieving pronounced DNA recovery. The quality and
      quantity of MHapNP-purified pDNA under optimal binding buffer conditions (0.5
      volume of 20% PEG 8000/2M NaCl) were comparable to those obtained using organic
      solvents or commercial kits. This MHapNP technique is rapid, simple, cost
      effective, and environmentally friendly and has the potential to extract DNA from
      other cell lysates.

PMID- 22465331
TI  - Detection of high-molecular-weight amyloid serum protein complexes using
      biological on-line tracer sedimentation.
AB  - The systemic amyloidoses are a rare but deadly class of protein folding disorders
      with significant unmet diagnostic and therapeutic needs. The current model for
      symptomatic amyloid progression includes a causative role for soluble toxic
      aggregates as well as for the fibrillar tissue deposits. Although much research
      is focused on elucidating the potential mechanism of aggregate toxicity, evidence
      to support their existence in vivo has been limited. We report the use of a
      technique we have termed biological on-line tracer sedimentation (BOLTS) to
      detect abnormal high-molecular-weight complexes (HMWCs) in serum samples from
      individuals with systemic amyloidosis due to aggregation and deposition of wild
      type transthyretin (senile systemic amyloidosis, SSA) or monoclonal
      immunoglobulin light chain (AL amyloidosis). In this proof-of-concept study,
      HMWCs were observed in 31 of 77 amyloid samples (40.3%). HMWCs were not detected
      in any of the 17 nonamyloid control samples subjected to BOLTS analyses. These
      findings support the existence of potentially toxic amyloid aggregates and
      suggest that BOLTS may be a useful analytic and diagnostic platform in the study
      of the amyloidoses or other diseases where abnormal molecular complexes are
      formed in serum.

PMID- 22465332
TI  - DNA extraction method with improved efficiency and specificity using DNA
      methyltransferase and "click" chemistry.
AB  - In an attempt to develop an alternative method to extract DNA from complex
      samples with much improved sensitivity and efficiency, here we report a proof-of
      concept work for a new DNA extraction method using DNA methyltransferase (Mtase)
      and "click" chemistry. According to our preliminary data, the method has improved
      the current methods by (i) employing a DNA-specific enzyme, TaqI DNA Mtase, for
      improved selectivity, and by (ii) capturing the DNA through covalent bond to the
      functionalized surface, enabling a broad range of treatments yielding the final
      sample DNA with minimal loss and higher purity such that it will be highly
      compatible with downstream analyses. By employing Mtase, a highly DNA specific
      and efficient enzyme, and click chemistry, we demonstrated that as little as 0.1
      fg of lambda-DNA (close to copy number 1) was captured on silica (Si)-based beads
      by forming a covalent bond between an azide group on the surface and the
      propargyl moiety on the DNA. This method holds promise in versatile applications
      where extraction of minute amounts of DNA plays critical roles such as basic and
      applied molecular biology research, bioforensic and biosecurity sciences, and
      state-of-the-art detection methods.

PMID- 22465333
TI  - Cooling-increased phospho-beta-arrestin-1 and beta-arrestin-1 expression levels
      in 3T3-L1 adipocytes.
AB  - Cooling induces several responses that are modulated by molecular inhibitors and
      activators and receptor signaling. Information regarding potential targets
      involved in cold response mechanisms is still insufficient. We examined levels of
      the receptor-signaling mediator beta-arrestin-1 and phospho-Ser-412 beta-arrestin
      1 in 3T3-L1 adipocytes exposed to 4-37  degrees C or treated with some molecular
      agents at 37 degrees C. We also cooled cells with or without modification and
      signal-modulating agents. These conditions did not decrease cell viability, and
      western blot analysis revealed that exposure to 4  degrees C for 1.5h and to 28
      and 32  degrees C for 24 and 48 h increased phospho-beta-arrestin-1 and beta
      arrestin-1 levels and that exposure to 4 and 18  degrees C for 3 and 4.5h
      increased beta-arrestin-1 level. Serum removal and rewarming abolished beta
      arrestin-1 alterations induced by cooling. Mithramycin A (a transcription
      inhibitor) treatment for 4 and 24h increased the level of beta-arrestin-1 but not
      that of phospho-beta-arrestin-1. The level of phospho-beta-arrestin-1 was
      increased by okadaic acid (a phosphatase inhibitor), decreased by epinephrine and
      aluminum fluoride (receptor-signaling modulators), and unaffected by N
      ethylmaleimide (an alkylating agent) at 37  degrees C. N-Ethylmaleimide and the
      receptor-signaling modulators did not alter beta-arrestin-1 expression at 37 
      degrees C but impaired the induction of phospho-beta-arrestin-1 at 28 and 32 
      degrees C without affecting the induction of beta-arrestin-1. We show that cold
      induced beta-arrestin-1 alterations are partially mimicked by molecular agents
      and that the responsive machinery for beta-arrestin-1 requires serum factors and
      N-ethylmaleimide-sensitive sites and is linked to rewarming- and receptor
      signaling-responsive machinery. Our findings provide helpful information for
      clarifying the cold-responsive machinery for beta-arrestin-1 and elucidating low
      temperature responses.

PMID- 22465334
TI  - Cryptosporidium tyzzeri and Cryptosporidium muris originated from wild West
      European house mice (Mus musculus domesticus) and East-European house mice (Mus
      musculus musculus) are non-infectious for pigs.
AB  - Three and 8 week old pigs were inoculated with Cryptosporidium muris HZ206 (Mus
      musculus musculus isolate), Cryptosporidium tyzerri CR2090 (M. m. musculus
      isolate) or C. tyzzeri CR4293 (isolate from a hybrid between Mus musculus
      domesticus and M. m. musculus) at a dose of 1 * 10(7) oocysts per animal.
      Inoculated pigs showed no detectable infection and no clinical symptoms of
      cryptosporidiosis during 30 days post infection (DPI), and no macroscopic changes
      were detected in the digestive tract following necropsy. Developmental stages
      were not detected in gastrointestinal tract tissue by histology or PCR throughout
      the duration of the experiment. The infectivity of isolates was verified on SCID
      mice, in which oocysts shedding started from 4 to 8 DPI. Based on our findings,
      it can be concluded that pigs are not susceptible to C. muris or C. tyzzeri
      infection.

PMID- 22465336
TI  - Biomimetic hydration lubrication with various polyelectrolyte layers on cross
      linked polyethylene orthopedic bearing materials.
AB  - Natural joints rely on fluid thin-film lubrication by the hydrated
      polyelectrolyte layer of cartilage. However, current artificial joints with
      polyethylene (PE) surfaces have considerably less efficient lubrication and thus
      much greater wear, leading to osteolysis and aseptic loosening. This is
      considered a common factor limiting prosthetic longevity in total hip
      arthroplasty (THA). However, such wear could be mitigated by surface modification
      to mimic the role of cartilage. Here we report the development of nanometer-scale
      hydrophilic layers with varying charge (nonionic, cationic, anionic, or
      zwitterionic) on cross-linked PE (CLPE) surfaces, which could fully mimic the
      hydrophilicity and lubricity of the natural joint surface. We present evidence to
      support two lubrication mechanisms: the primary mechanism is due to the high
      level of hydration in the grafted layer, where water molecules act as very
      efficient lubricants; and the secondary mechanism is repulsion of protein
      molecules and positively charged inorganic ions by the grafted polyelectrolyte
      layer. Thus, such nanometer-scaled hydrophilic polymers or polyelectrolyte layers
      on the CLPE surface of acetabular cup bearings could confer high durability to
      THA prosthetics.

PMID- 22465335
TI  - A protein transduction method using oligo-arginine (3R) for the delivery of
      transcription factors into cell nuclei.
AB  - Protein transduction with cell-penetrating peptides such as poly-arginine and HIV
      TAT peptides is widely used to deliver proteins, peptides, siRNA and biologically
      active compounds. It has been thought that poly-arginine peptides transduce
      proteins in a manner dependent on the number of arginine residues and oligo
      peptides such as three arginines (3R) are ineffective. Here we showed that 3R
      fused proteins were effectively delivered and functioned in cells co-treated with
      pyrenebutyrate, a counteranion bearing an aromatic hydrophobic moiety. Little 3R
      was transduced in glioma cells without pyrenebutyrate whereas the oligo-arginine
      was effectively delivered with pyrenebutyrate. Enhanced green fluorescence
      protein (eGFP) fused with 3R was effectively delivered into various kinds of
      cells including primary cultured cells and suspended cells in the presence of
      pyrenebutyrate. p53 fused with 3R (3R-p53) was delivered into glioma cells
      without pyrenebutyrate but could not be translocated into the nucleus. In
      contrast, 3R-p53 was observed in nuclei of glioma cells when co-applied with
      pyrenebutyrate. Although 3R-p53 was delivered less effectively than 11R-p53 with
      pyrenebutyrate, its transcriptional activity was higher than that of 11R-p53.
      Moreover, a single administration of 3R-p53 with pyrenebutyrate significantly
      inhibited the growth of cancer cells. These results suggest protein transduction
      using an oligo-arginine (3R) with pyrenebutyrate to be a good tool for the
      delivery of functional transcription factors and a promising method of treating
      cancer.

PMID- 22465337
TI  - Decellularized homologous tissue-engineered heart valves as off-the-shelf
      alternatives to xeno- and homografts.
AB  - Decellularized xenogenic or allogenic heart valves have been used as starter
      matrix for tissue-engineering of valve replacements with (pre-)clinical promising
      results. However, xenografts are associated with the risk of immunogenic
      reactions or disease transmission and availability of homografts is limited.
      Alternatively, biodegradable synthetic materials have been used to successfully
      create tissue-engineered heart valves (TEHV). However, such TEHV are associated
      with substantial technological and logistical complexity and have not yet entered
      clinical use. Here, decellularized TEHV, based on biodegradable synthetic
      materials and homologous cells, are introduced as an alternative starter matrix
      for guided tissue regeneration. Decellularization of TEHV did not alter the
      collagen structure or tissue strength and favored valve performance when compared
      to their cell-populated counterparts. Storage of the decellularized TEHV up to 18
      months did not alter valve tissue properties. Reseeding the decellularized valves
      with mesenchymal stem cells was demonstrated feasible with minimal damage to the
      reseeded valve when trans-apical valve delivery was simulated. In conclusion,
      decellularization of in-vitro grown TEHV provides largely available off-the-shelf
      homologous scaffolds suitable for reseeding with autologous cells and trans
      apical valve delivery.

PMID- 22465338
TI  - Tailoring the immune response by targeting C-type lectin receptors on alveolar
      macrophages using "pathogen-like" amphiphilic polyanhydride nanoparticles.
AB  - C-type lectin receptors (CLRs) offer unique advantages for tailoring immune
      responses. Engagement of CLRs regulates antigen presenting cell (APC) activation
      and promotes delivery of antigens to specific intracellular compartments inside
      APCs for efficient processing and presentation. In these studies, we have
      designed an approach for targeted antigen delivery by decorating the surface of
      polyanhydride nanoparticles with specific carbohydrates to provide pathogen-like
      properties. Two conserved carbohydrate structures often found on the surface of
      respiratory pathogens, galactose and di-mannose, were used to functionalize the
      surface of polyanhydride nanoparticles and target CLRs on alveolar macrophages
      (AMphi), a principle respiratory tract APC. Co-culture of functionalized
      nanoparticles with AMphi significantly increased cell surface expression of MHC I
      and II, CD86, CD40 and the CLR CIRE over non-functionalized nanoparticles. Di
      mannose and galactose functionalization also enhanced the expression of the
      macrophage mannose receptor (MMR) and the macrophage galactose lectin,
      respectively. This enhanced AMphi activation phenotype was found to be dependent
      upon nanoparticle internalization. Functionalization also promoted increased
      AMphi production of the pro-inflammatory cytokines IL-1beta, IL-6 and TNF-alpha.
      Additional studies demonstrated the requirement of the MMR for the enhanced
      cellular uptake and activation provided by the di-mannose functionalized
      nanoparticles. Together, these data indicate that targeted engagement of MMR and
      other CLRs is a viable strategy for enhancing the intrinsic adjuvant properties
      of nanovaccine adjuvants and promoting robust pulmonary immunity.

PMID- 22465339
TI  - Successful treatment of acyclovir-resistant herpes simplex virus type 2 proctitis
      with leflunomide in an HIV-infected man.
AB  - Human herpes simplex virus infections are very common and represent significant
      morbidity in the immunocompromised host. Patients with acyclovir resistant
      strains of HSV based on viral thymidine kinase gene mutations need alternative
      therapeutic approaches. Leflunomide has been shown to possess antiviral activity
      against several viruses. Herein we describe a case of acyclovir resistant HSV-2
      proctitis in an HIV patient successfully treated with leflunomide without
      significant side effects.

PMID- 22465340
TI  - Two laboratory-confirmed cases of Japanese encephalitis imported to Germany by
      travelers returning from Southeast Asia.
AB  - Japanese encephalitis virus is the leading cause of encephalitis in Asia and
      parts of the Pacific. Despite the high number of symptomatic infections in
      endemic countries, clinical disease in travelers is rare. However, an increasing
      number of imported infections from popular holiday destinations in Southeast Asia
      have been recorded in the past few years, including serious disease courses in
      short-term travelers. Here we report two severe, non-fatal cases in tourists, who
      returned from a long-time stay in Thailand and a short-term trip to Bali,
      Indonesia, respectively. Recommendations for vaccination and pre-travel advice
      are discussed.

PMID- 22465341
TI  - Value of herpes simplex virus type-specific serology: a case report.
AB  - Genital herpes, usually caused by herpes simplex virus type 2 (HSV-2), is one of
      the most common sexually transmitted diseases in humans. By contrast,
      intrauterine HSV-2 infections have been described rarely in the literature. Our
      report describes a case of neonate who was delivered after 30+2 gestational weeks
      by cesarean section. He presented with a respiratory distress syndrome resulting
      in broncho-pulmonary dysplasia. At the age of 6 weeks, a chorioretinal scar was
      detected. During the 4th month of age, the infant developed recurrent HSV-2
      infection with nasal lesions. The retrospective type-specific serologic diagnosis
      revealed previous HSV-2 infection of the mother resulting in prenatal HSV-2
      infection of the infant. In conclusion, intrauterine HSV-2 infections may be
      underrepresented since they may not be associated with severe congenital
      malformations and the diagnosis requires the use of HSV type-specific serologic
      methods not widely applied in microbiological laboratories.

PMID- 22465342
TI  - Spatiotemporal expression pattern of KIF21A during normal embryonic development
      and in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).
AB  - Congenital fibrosis of the extraocular muscles type 1 (CFEOM1) is a rare
      inherited strabismus syndrome characterized by non-progressive ophthalmoplegia.
      We previously identified that CFEOM1 results from heterozygous missense mutations
      in KIF21A, which encodes a kinesin motor protein. Here we evaluate the expression
      pattern of KIF21A in human brain and muscles of control and CFEOM1 patients, and
      during human and mouse embryonic development. KIF21A is expressed in the cell
      bodies, axons, and dendrites of many neuronal populations including those in the
      hippocampus, cerebral cortex, cerebellum, striatum, and motor neurons of the
      oculomotor, trochlear, and abducens nuclei from early development into maturity,
      and its spatial distribution is not altered in the CFEOM1 tissues available for
      study. Multiple splice isoforms of KIF21A are identified in human fetal brain,
      but none of the reported CFEOM1 mutations are located in or near the
      alternatively spliced exons. KIF21A immunoreactivity is also observed in
      extraocular and skeletal muscle biopsies of control and CFEOM1 patients, where it
      co-localizes with triadin, a marker of the excitation-contractile coupling
      system. The diffuse and widespread expression of KIF21A in the developing human
      and mouse central and peripheral nervous system as well as in extraocular muscle
      does not account for the restricted ocular phenotype observed in CFEOM1, nor does
      it permit the formal exclusion of a myogenic etiology based on expression
      patterns alone.

PMID- 22465344
TI  - Oxidative stress markers and cardiovascular disease: advantage of using these
      factors in combination with lifestyle factors for cardiovascular risk assessment.

PMID- 22465343
TI  - Isoproterenol induced hypertrophy and associated signaling pathways are modulated
      by somatostatin in H9c2 cells.
AB  - BACKGROUND: Somatostatin (SST), a growth hormone inhibitory peptide plays key
      role in regulation of cell proliferation via modulation of mitogen activated
      protein kinases (MAPKs) and cell survival pathway. In cardiac physiology, beta
      Adrenergic receptors (beta-ARs) play crucial role in regulation of downstream
      signaling pathways in receptor specific manner. The aim of the current study was
      to delineate the mechanistic insight for the role of SST on beta-AR mediated
      signaling which promotes hypertrophy and apoptosis in rat fetal cardiomyocytes
      (H9c2 cells). Accordingly, SST dependent changes in signaling molecules including
      second messenger cAMP, PKA/CREB as well as MAPKs including ERK and p38 which are
      key mediators of hypertrophy and apoptosis were analyzed. METHODS AND RESULTS: In
      the present study, we determined receptor specific effects on intracellular cAMP
      levels, signaling by western blot analysis and apoptosis by using JC-1 and
      Hoechst-33258 staining. Here, we present the data which indicates that SST
      inhibits isoproterenol induced hypertrophy and apoptosis in H9c2 cells.
      Importantly, SST inhibits beta-ARs agonist induced cAMP activation and SST
      mediated inhibition of cAMP was enhanced in presence of beta-ARs antagonist. SST
      enhances beta2AR agonist formoterol mediated effects on PKA, CREB and ERK1/2
      phosphorylations whereas it inhibits isoproterenol mediated ERK1/2 and p38
      signaling in concentration dependent manner. CONCLUSIONS: Taken together, these
      results presented here provide a novel insight for the potential role of SST in
      regulation of beta-AR mediated effects on hypertrophy and modulation of
      hypertrophy promoting signaling in H9c2 cells.

PMID- 22465345
TI  - Static magnetic fields increase cardiomyocyte differentiation of Flk-1+ cells
      derived from mouse embryonic stem cells via Ca2+ influx and ROS production.
AB  - AIMS: To investigate the effects of static magnetic fields (MFs) on
      cardiomyogenesis of mouse embryonic stem (ES) cell-derived embryoid bodies and
      Flk-1(+) cardiac progenitor cells and to assess the impact of cytosolic calcium
      [Ca(2+)]c and reactive oxygen species (ROS). METHODS AND RESULTS: Embryoid bodies
      and ES cell-derived Flk-1(+) cardiovascular progenitor cells were exposed to
      static MFs. The expression of cardiac genes was evaluated by RT-PCR; sarcomeric
      structures were assessed by immunohistochemistry; intracellular ROS and [Ca(2+)]c
      of ES cells were examined by H2DCF-DA- and fluo-4-based microfluorometry.
      Treatment of embryoid bodies with MFs dose-dependent increased the number of
      contracting foci and cardiac areas as well as mRNA expression of the cardiac
      genes MLC2a, MLC2v, alpha-MHC and beta-MHC. In Flk-1(+) cells MFs (1 mT) elevated
      both [Ca(2+)]c and ROS, increased expression of the cardiogenic transcription
      factors Nkx-2.5 and GATA-4 as well as cardiac genes. This effect was due to
      Ca(2+) influx, since extracellular Ca(2+) chelation abrogated ROS production and
      MF-induced cardiomyogenesis. Furthermore absence of extracellular calcium
      impaired sarcomere structures. Neither the phospholipase C inhibitor U73122 nor
      thapsigargin inhibited MF-induced increase in [Ca(2+)]c excluding involvement of
      intracellular calcium stores. ROS were generated through NAD(P)H oxidase, since
      NOX-4 but not NOX-1 and NOX-2 mRNA was upregulated upon MF exposure. Ablation of
      NOX-4 by sh-RNA and treatment with the NAD(P)H oxidase inhibitor diphenylen
      iodonium (DPI) totally abolished MF-induced cardiomyogenesis. CONCLUSION: The
      ability of static MFs to enhance cardiomyocyte differentiation of ES cells allows
      high throughput generation of cardiomyocytes without pharmacological or genetic
      modification.

PMID- 22465346
TI  - Double product and end-organ damage in African and Caucasian men: the SABPA
      study.
AB  - BACKGROUND: Increasing urbanisation in sub-Saharan African countries is causing a
      rapid increase in cardiovascular disease. Evidence suggests that Africans have
      higher blood pressures and a higher prevalence of hypertension-related
      cardiovascular morbidity and mortality, compared to Caucasians. We investigated
      double product (systolic blood pressure * heart rate), a substantial measure of
      cardiac workload, as a possible cardiovascular risk factor in African and
      Caucasian men. MATERIAL AND METHODS: The study consisted of 101 urbanised African
      and 101 Caucasian male school teachers. We measured 24h ambulatory blood pressure
      and the carotid cross-sectional wall area, and determined left ventricular
      hypertrophy electrocardiographically by means of the Cornell product. Urinary
      albumin and creatinine were analysed to obtain the albumin-to-creatinine ratio.
      RESULTS: Africans had higher 24h, daytime and nighttime systolic- and diastolic
      blood pressure, heart rate and resultant double product compared to the
      Caucasians. In addition, markers of end-organ damage, albumin-to-creatinine ratio
      and left ventricular hypertrophy were higher in the Africans while cross
      sectional wall area did not differ. In Africans after single partial and multiple
      regression analysis, 24h systolic blood pressure, but not double product or heart
      rate, correlated positively with markers of end-organ damage (cross-sectional
      wall area: beta=0.398, P=0.005; left ventricular hypertrophy: beta=0.455,
      P<0.001; albumin-to-creatinine ratio: beta=0.280, P=0.012). No associations were
      evident in Caucasian men. CONCLUSIONS: Double product may not be a good marker of
      increased cardiovascular risk when compared to systolic blood pressure in African
      and Caucasian men.

PMID- 22465347
TI  - Berberine improves endothelial function by reducing endothelial microparticles
      mediated oxidative stress in humans.
AB  - BACKGROUND: Circulating endothelial microparticles (EMPs) lead to endothelial
      dysfunction by increasing oxidative stress. Berberine has a beneficial effect on
      endothelial function, but no data are available on the EMP-mediated oxidative
      stress. The present study tests the hypothesis that berberine contributes to the
      improvement of endothelial function in humans via inhibiting EMP-mediated
      oxidative stress in vascular endothelium. METHODS: Twelve healthy subjects
      received a 1-month berberine therapy and eleven healthy subjects served as
      control. Endothelium-dependent and -independent function in the brachial artery
      was assessed by flow-mediated vasodilation (FMD) and sublingual nitroglyceride
      mediated vasodilation (NMD). Circulating EMPs and serum malondialdehyde (MDA)
      were measured before and after therapy. Furthermore, in vitro human umbilical
      vein endothelial cells (HUVECs) were stimulated by EMPs with or without presence
      of anti-oxidant compound apocynin or berberine. Intracellular reactive oxygen
      species (ROS), nitric oxide (NO) production and NADPH oxidase 4 (Nox4) protein
      expressions were examined, respectively. RESULTS: The levels of serum MDA and
      circulating CD31+/CD42- MPs were significantly reduced in the berberine group
      compared with the control group, which were associated with improvement of FMD.
      The EMPs in vitro facilitated ROS production and Nox4 protein expression and
      reduced NO synthesis in HUVECs. These alterations can be reversed by the presence
      of apocynin or berberine, respectively. CONCLUSION: The present study
      demonstrated for the first time that EMP-induced upregulation of Nox4 expression
      may enhance ROS production in HUVECs. Berberine treatment contributes to the
      amelioration of endothelial function through a partially reducing oxidative
      stress of vascular endothelium induced by circulating CD31+/CD42- microparticles
      in humans.

PMID- 22465348
TI  - The shape and function of the right ventricle in Ebstein's anomaly.
AB  - BACKGROUND: Ebstein's anomaly involves both the right ventricle (RV) and
      tricuspid valve. METHODS: The functional RV and tricuspid orifice were traced
      from magnetic resonance images in 29 adult Ebstein patients and 9 normal subjects
      and reconstructed for visualization and measurement of regional RV size,
      function, and shape at 20 cross sections, and inlet and outflow tract ejection
      fractions (EFs). RESULTS: The RV in Ebstein's had RV dilation (end diastolic
      volume index 179 +/- 69 vs. 84 +/- 22 ml/m(2) in normals, p<0.001) and global
      dysfunction (EF 45 +/- 8 vs. 55 +/- 5% in normals, p<0.001). Longitudinal
      contraction was preserved (26 +/- 13 vs. 26 +/- 4 mm in normals) and correlated
      more weakly with EF than short axis fractional shortening (r=0.44 vs. r=0.71,
      p<0.05 for both). The apical region in Ebstein's RV was enlarged, rounded and
      contributed more than normal to the global stroke volume. However this
      contribution correlated inversely with global EF. In contrast slices in the basal
      region had normal cross sectional area and their function correlated directly
      with global EF. Inlet EF was depressed (46 +/- 8% vs. 55 +/- 6 in normals,
      p=.002); outflow tract EF was even more depressed (39 +/- 14, p=0.019).
      CONCLUSION: The three dimensional shape of the RV in adult Ebstein patients was
      demonstrated. The Ebstein's RV remodels in diverse regional patterns rather than
      following a shape continuum. Changes at the apex and base had opposing effects on
      function. Global EF was supported more by short axis than longitudinal
      contraction.

PMID- 22465349
TI  - Sympathectomy as a treatment for refractory coronary artery spasm.

PMID- 22465350
TI  - It took a RedBull to unmask Brugada syndrome.

PMID- 22465352
TI  - Age-dependent care and long-term (20 year) mortality of 14,434 myocardial
      infarction patients: changes from 1985 to 2008.
AB  - OBJECTIVES: To determine whether age-dependent inequalities in care and outcome
      changed over a 24 year period for patients admitted with a myocardial infarction
      (MI). METHODS: We examined four age groups (<55, 55-65, 65-75, and >75 years) and
      treatment and mortality in 14,434 consecutive patients admitted for MI to an
      intensive coronary care unit from 1985 to 2008. Temporal trend analyses were
      performed by comparing decades of admission (1985-1990 vs. 1990-2000 vs. 2000
      2008). RESULTS: A total of 2040 (14%) of the patients were >75 years of age.
      Older patients more often were female and less often presented with an ST-segment
      elevation MI (STEMI). Systematic differences in care were present between the age
      groups: older patients were less likely to receive evidence-based medical care
      and reperfusion therapy during the last 24 years, although the differences became
      smaller over time. In 2000-2008, 30-day (adjusted OR 0.28, 95%CI: 0.23-0.34) and
      5-year (adjusted HR 0.61, 95%CI: 0.54-0.68) mortality were lower compared to 1985
      1990. These temporal trends were equal across all age groups. Hence, the change
      in mortality over the 24-year study period is similar among the spectrum of ages.
      Patients aged <55, 55-65, 65-75, and >75 years had a 20-year mortality of 38, 63,
      87 and >95%, respectively. CONCLUSIONS: Older patients with an MI remained less
      likely to receive evidence-based care during 24 years of observation. Temporal
      reductions in mortality were similar among all age groups. The application of
      proven MI therapies to appropriate patients regardless of age may even further
      improve these outcomes.

PMID- 22465351
TI  - Suboptimal response to clopidogrel and the effect of prasugrel in acute coronary
      syndromes.
AB  - BACKGROUND: High on clopidogrel platelet reactivity (HPR) has been associated
      with adverse outcomes following acute coronary syndromes (ACS). This study
      investigated the rate of HPR in a New Zealand ACS population and examined the
      effectiveness of prasugrel in reducing platelet reactivity in those with HPR.
      METHODS: In this prospective cohort study, 250 patients with ACS were pretreated
      with aspirin and clopidogrel and residual platelet reactivity was measured using
      whole blood multiple electrode platelet aggregometry. Twenty-seven of the
      patients with HPR were treated with prasugrel at the discretion of their
      physician, and platelet reactivity retested. RESULTS: Ninety-five patients (38%)
      had HPR. Maori and Pacific Island patients had a higher rate of HPR compared to
      Europeans (57% versus 35.9%, p=0.013). Additionally, patients with diabetes were
      also found to have higher rate of HPR compared to non-diabetics (50% versus
      34.8%, p=0.045). Patients treated with a low dose clopidogrel regimen had
      significantly higher rates of HPR (45.4%) compared to those treated with
      intermediate (25.4%) or high dose regimens (26.8%, p=0.009). All of the 27
      patients with HPR who were subsequently treated with prasugrel (60 mg) had a
      significant decrease in platelet reactivity (660 AU min (565-770) before versus
      230 AU min (110-345) after, p<0.001), and was reduced to below the HPR cutoff in
      24 (88.9%) of the patients. CONCLUSIONS: Ethnicity, diabetes and clopidogrel dose
      contributed to HPR. The use of prasugrel in those with HPR resulted in a
      consistent and marked reduction in platelet reactivity.

PMID- 22465353
TI  - Estimating covariation between vital rates: a simulation study of connected vs.
      separate generalized linear mixed models (GLMMs).
AB  - Covariation between vital rates is recognized as an important pattern to be
      accounted for in demographic modeling. We recently introduced a model for
      estimating vital rates and their covariation as a function of known and unknown
      effects, using generalized linear mixed models (GLMM's) implemented in a
      hierarchical Bayesian framework (Evans et al., 2010) In particular, this model
      included a model-wide year effect (YEAR) influencing all vital rates, which we
      used to estimate covariation between vital rates due to exogenous factors not
      directly included in the model. This YEAR effect connected the GLMMs of vital
      rates into one large model; we refer to this as the "connected GLMMs" approach.
      Here we used a simulation study to evaluate the performance of a simplified
      version of this model, compared to separate GLMMs of vital rates, in terms of
      their ability to estimate correlations between vital rates. We simulated data
      from known relationships between vital rates and a covariate, inducing
      correlations among the vital rates. We then estimated those correlations from the
      simulated data using connected vs. separate GLMMs with year random effects. We
      compared precision and accuracy of estimated vital rates and their correlations
      under three scenarios of the pervasiveness of the exogenous effect (and thus true
      correlations). The two approaches provide equally good point estimates of vital
      rate parameters, but connected GLMMs provide better estimates of covariation
      between vital rates than separate GLMMs, both in terms of accuracy and precision,
      when the common influence on vital rates is pervasive. We discuss the situations
      where connected GLMMs might be best used, as well as further areas of
      investigation for this approach.

PMID- 22465354
TI  - Effects of the protein synthesis inhibitor cycloheximide on anxiety-like
      extinction behavior in an animal model of post-traumatic stress.
AB  - The effect of cycloheximide (CXM), a protein synthesis inhibitor, on memory
      reconsolidation and extinction was explored in rats using a model of post
      traumatic stress. Forty-two animals were exposed to predator stress followed by
      1, 2, or 4 extinction trials. Saline or CXM (1 mg/kg) was administered following
      the last extinction trial and anxiety was measured in the elevated-plus maze
      (EPM) seventy-two hours later. Saline control animals exhibited elevated anxiety
      levels in comparison to a no stress control group. Cycloheximide appeared to
      maintain stress-induced anxiety responses, which otherwise declined with repeated
      extinction trials in the saline control groups. These findings suggest that
      cycloheximide may have induced amnesia for extinction, leaving the target memory
      of the predatory stress intact resulting in elevated levels of anxiety. The
      relationships between de novo protein synthesis and reconsolidation of anxiety
      related memories following extinction trials may be more complex than originally
      thought.

PMID- 22465355
TI  - Physician experiences transitioning between an older versus newer electronic
      health record for electronic prescribing.
AB  - PURPOSE: Federal incentives to adopt interoperable, certified electronic health
      records (EHRs) with electronic prescribing (e-prescribing) are motivating
      providers using older EHRs to transition to newer EHRs. The objective of this
      study was to describe, from the perspective of experienced EHR users, the
      transition from an older, locally developed EHR with minimal clinical decision
      support (CDS) for e-prescribing to a newer, commercial EHR with more robust CDS
      for e-prescribing. METHODS: This qualitative, case study consisted of
      observations and semi-structured interviews of adult internal medicine faculty
      members (n=19) at an academic-affiliated ambulatory care clinic from January
      through November 2009. All providers transitioned from the older, locally
      developed EHR to the newer, commercial EHR in April 2008. We analyzed field notes
      of observations and transcripts of semi-structured interviews using qualitative
      methods guided by a grounded theory approach. RESULTS: We identified key themes
      describing physician experiences. Despite intensive effort by the information
      systems team to ease the transition, even these experienced e-prescribers found
      transitioning extremely difficult. The commercial EHR was not perceived as
      improving medication safety, despite having more robust CDS. Additionally,
      physicians felt the commercial EHR was too complex, reducing their efficiency.
      CONCLUSIONS: This is among the first studies examining physician experiences
      transitioning between an older, locally developed EHR to a newer, commercial EHR
      with more robust CDS for e-prescribing. Understanding physician experiences with
      this type of transition and their general preferences for prescribing
      applications may lead to less disruptive system implementations and better
      designed EHRs that are more readily accepted by providers. In this way,
      productivity and safety benefits may be maximized while mitigating potential
      threats associated with transitions. TRIAL REGISTRATION: ClinicalTrials.gov,
      Identifier: NCT00603070.

PMID- 22465356
TI  - Cell volume changes during apoptosis monitored in real time using digital
      holographic microscopy.
AB  - Cellular volume changes play important roles in many processes associated with
      the normal cell activity, as well as various diseases. Consequently, there is a
      considerable need to accurately measure volumes of both individual cells and cell
      populations as a function of time. In this study, we have monitored cell volume
      changes in real time during apoptosis using digital holographic microscopy. Cell
      volume changes were deduced from the measured phase change of light transmitted
      through cells. Our digital holographic experiments showed that after exposure to
      1 MUM staurosporine for 4 h, the volumes of KB cells were reduced by ~50-60%,
      which is consistent with previous results obtained using electronic cell sizing
      and atomic force microscopy. In comparison with other techniques, digital
      holographic microscopy is advantageous because it employs noninvasive detection,
      has high time resolution, real time measurement capability, and the ability to
      simultaneously investigate time-dependent volume changes of both individual cells
      and cell populations.

PMID- 22465357
TI  - Lipidomic analysis of the liver identifies changes of major and minor lipid
      species in adiponectin deficient mice.
AB  - Adiponectin protects from hepatic fat storage but adiponectin deficient mice (APN
      /-) fed a standard chow do not develop liver steatosis. This indicates that other
      pathways might be activated to compensate for adiponectin deficiency. An unbiased
      and comprehensive screen was performed to identify hepatic alterations of lipid
      classes in these mice. APN-/- mice had decreased hepatic cholesteryl esters while
      active SREBP2 and systemic total cholesterol were not altered. Upregulation of
      cytochromes for bile acid synthesis suggests enhanced biliary cholesterol
      excretion. Analysis of 37 individual fatty acid species showed reduced stearate
      whereas total fatty acids were not altered. Total amount of triglycerides and
      phospholipids were equally abundant. A selective increase of monounsaturated
      phosphatidylcholine and phosphatidylethanolamine which positively correlate with
      hepatic and systemic triglycerides with the latter being elevated in APN-/- mice,
      was identified. Stearoyl-CoA desaturase 1 (SCD1) is involved in the synthesis of
      monounsaturated fatty acids and despite higher mRNA expression enzyme activity
      was not enhanced. Glucosylceramide postulated to contribute to liver damage was
      decreased. This study demonstrates that adiponectin deficiency is associated with
      hepatic changes in lipid classes in mice fed a standard chow which may protect
      from liver steatosis.

PMID- 22465359
TI  - Association of CfLGBP gene polymorphism with disease susceptibility/resistance of
      Zhikong scallop (Chlamys farreri) to Listonella anguillarum.
AB  - Lipopolysaccharide and beta-1, 3-glucan binding protein (LGBP) is a pattern
      recognition receptor (PRR) recognizing and binding both LPS and beta-1, 3-glucan,
      playing important roles in innate immunity. In the present study, the single
      nucleotide polymorphisms (SNPs) were assessed in LGBP gene from scallop Chlamys
      farreri (designated CfLGBP), and eight SNPs were found in its potential LPS and
      glucanase binding motif. The locus +7679 with the transition of G-A, which
      produced an amino acid substitution at codon 360 from a non polar Glycine to
      polar Serine, was selected to inspect their association with disease
      resistance/susceptibility to Listonella anguillarum. Three genotypes G/G, G/A and
      A/A, were revealed at locus +7679, and their frequencies were 89.7%, 7.7% and
      2.6% in the resistant stock, while 63.2%, 34.2% and 2.6% in the susceptible
      stock, respectively. The frequency of genotypes G/G and G/A were significantly
      different (P < 0.05) between the two stocks. The pathogen-associated molecular
      patterns (PAMP) binding activity of two recombinant proteins, rCfLGBP (G) with G
      variant at locus +7679 and rCfLGBP (S) with A variant at locus +7679, were
      elucidated by ELISA assay. The binding affinities of both LPS and beta-glucan
      binding affinity were varied in a dose-dependent manner, where the binding
      affinity of rCfLGBP (G) was significantly higher than that of rCfLGBP (S) (P <
      0.05). The results collectively suggested that the polymorphism of +7679 G/G in
      CfLGBP possibly enhances the binding activity of LPS and beta-glucan, and was
      associated to disease resistance of scallop against L. anguillarum, which could
      be a potential marker applied in future selection of scallop with enhanced
      resistance to L. anguillarum.

PMID- 22465358
TI  - Mallory-Denk bodies form when EZH2/H3K27me3 fails to methylate DNA in the nuclei
      of human and mice liver cells.
AB  - EZH2/H3K27me3 and polycomb group complex (PcG) play a major role in regulating
      global gene expression including tumor suppressor genes. EZH2 is linked to cell
      cycle regulated EZH2 phosphorylation by CDK1, a mitotic kinase which increases in
      arrested mitosis compared to S phase. CDK1 phosphorylation of EZH2 accelerates
      the degradation of pEZH2. Phospho-EZH2 is subjected to ubiquitination. The half
      like of pEZH2 is shorter when compared to total EZH2. In the present study, pEZH2
      was found concentrated together with ubiquitin in the Mallory-Denk bodies (MDB)
      that were formed in hepatocytes in the livers of drug primed mice refed DDC and
      humans with alcoholic hepatitis or hepatocellular carcinoma. The cells that
      formed MDBs in the mice livers studied were associated with a growth advantage
      and a high proliferative index. However, the livers from patients with alcoholic
      hepatitis showed evidence of cell cycle arrest where PCNA, cyclin D1 and p27
      positive nuclei were numerous but Ki-67 positive nuclei were scarce. It is
      concluded that MDB formation is linked to the cell cycle and global gene
      expression (i.e. loss of gene silencing) through its association with the
      regulation of the polycomb group PRC2/EZH2/H3K27me3 complex.

PMID- 22465361
TI  - Effects of dietary supplementation of potential probiotic Pseudomonas aeruginosa
      VSG-2 on the innate immunity and disease resistance of tropical freshwater fish,
      Labeo rohita.
AB  - The effects of dietary Pseudomonas aeruginosa VSG-2 supplementation on innate
      immunity and protection against Aeromonas hydrophila infection were evaluated in
      Labeo rohita. Fish were fed for 60 days with control diet or 3 experimental diets
      containing P. aeruginosa VSG-2 at 10(5), 10(7), and 10(9) cfu g(-l),
      respectively. Various innate immune parameters were examined at 30 and 60 days
      post-feeding. Fish were challenged with A. hydrophila 60 days post-feeding and
      mortalities were recorded over 10 days post-infection. Dietary supplementation of
      P. aeruginosa VSG-2 significantly increased serum lysozyme and alternative
      complement pathway (ACP) activities, phagocytosis, and respiratory burst activity
      in head kidney macrophages of L. rohita throughout the experimental period.
      Superoxide dismutase (SOD) activity significantly increased after 60 days in the
      groups fed diets containing 10(7) and 10(9) cfu g(-1) P aeruginosa. Serum IgM
      levels were significantly higher in the treatment groups than in the control
      group after 30 days of feeding; however, the opposite result was observed at 60
      days. Moreover, fish fed diets containing 10(7) and 10(9) cfu g(-1)P. aeruginosa
      had significantly higher post-challenge survival rates against A. hydrophila
      infection. Further, P. aeruginosa VSG-2 was found to be safe for mammals. These
      results indicate that dietary P. aeruginosa VSG-2 supplementation at 10(7) cfu g(
      1) can effectively improve innate immunity and disease resistance in L. rohita.

PMID- 22465360
TI  - Gene expression and protein levels of thioredoxin in the gills from the whiteleg
      shrimp (Litopenaeus vannamei) infected with two different viruses: the WSSV or
      IHHNV.
AB  - The thioredoxin (TRX) system in crustaceans has demonstrated to act as a cell
      antioxidant being part of the immune response by dealing with the increased
      production of reactive oxygen species during bacterial or viral infection. Since
      the number of marine viruses has increased in the last years significantly
      affecting aquaculture practices of penaeids, and due to the adverse impact on
      wild and cultured shrimp populations, it is important to elucidate the dynamics
      of the shrimp response to viral infections. The role of Litopenaeus vannamei
      thioredoxin (LvTRX) was compared at both, mRNA and protein levels, in response to
      two viruses, the white spot syndrome virus (WSSV) and the infectious hypodermal
      and hematopoietic necrosis virus (IHHNV). The results confirmed changes in the
      TRX gene expression levels of WSSV-infected shrimp, but also demonstrated a more
      conspicuous response of TRX to WSSV than to IHHNV. While both the dimeric and
      monomeric forms of LvTRX were detected by Western blot analysis during the WSSV
      infection, the dimer on its reduced form was only detected through the IHHNV
      infectious process. These findings indicate that WSSV or IHHNV infected shrimp
      may induce a differential response of the LvTRX protein.

PMID- 22465362
TI  - cDNA microarray analysis of disk abalone genes in gills and hemocytes after viral
      hemorrhagic septicemia virus (VHSV) challenge.
AB  - A disk abalone Haliotis discus discus 4.2 K cDNA microarray was designed by
      selecting abalone expressed sequence tags (ESTs). Transcriptional profiles in
      gills and hemocytes were analyzed upon abalone challenged with viral hemorrhagic
      septicemia virus (VHSV) in order to select candidates for screening of immune
      response genes. Among the 4188 genes analyzed, 280 (6.6%) transcripts were
      changed their expression level in gills and hemocytes against VHSV challenge
      compared to control animals. Total of 88 and 65 genes were up-regulated in gills
      and hemocytes, respectively. These genes can be grouped under various immune
      functional categories such as transcription factors (Kruppell-like factor; ETS
      family transcription factor), inflammatory and apoptosis related genes (TNF
      superfamily members, Fas ligand), IFN regulatory proteins (IFN-44 like,
      interferon gamma-inducible lysosomal thiol reductase) and detoxification proteins
      (glutathione peroxidase). In contrast, 25 and 102 genes were shown down
      regulation in gills and hemocytes, respectively. Among the differentially
      expressed transcripts, considerably higher numbers of ESTs were represented as
      either hypothetical (unknown) proteins or no GenBank match suggesting those may
      be novel genes associated with internal defense of abalone.

PMID- 22465363
TI  - Treatment of serous macular detachment associated with circumscribed choroidal
      hemangioma.
AB  - PURPOSE: To evaluate the effects of transpupillary thermotherapy and intravitreal
      bevacizumab injection on serous macular detachment and cystoid macular edema
      (CME) associated with circumscribed choroidal hemangioma. DESIGN: Retrospective,
      interventional case series. METHODS: We reviewed the records of 12 patients with
      circumscribed choroidal hemangioma treated with transpupillary thermotherapy
      and/or intravitreal injection of bevacizumab. We assessed changes in best
      corrected visual acuity (BCVA), central foveal thickness by optical coherence
      tomography, and resolution of serous macular detachment and CME. RESULTS: Six of
      8 patients treated with transpupillary thermotherapy showed complete resolution
      of serous macular detachment and CME and the median minimal angle of resolution
      (logMAR) BCVA improved from 0.85 to 0.35 (P = .026). Among these 6 patients, 1
      had no recurrence for 86 months and 5 had sustained resolution of serous macular
      detachment for a mean duration of 32.8 months before recurrence. Among the 9
      patients treated with bevacizumab (including 5 patients who had transpupillary
      thermotherapy as a primary treatment), 5 showed resolution of serous macular
      detachment and the median logMAR BCVA improved from 0.7 to 0.5 (P = .042). Among
      these 5 patients, 3 had sustained resolution for a mean duration of 5.7 months
      and 2 showed recurrent serous macular detachment after 3 and 12 months.
      CONCLUSION: Transpupillary thermotherapy and intravitreal bevacizumab appear
      effective in the management of symptomatic circumscribed choroidal hemangioma,
      although recurrence of serous macular detachment and CME developed after long
      term follow-up of transpupillary thermotherapy, and the duration of treatment
      effectiveness appears to be short with bevacizumab.

PMID- 22465365
TI  - Descemet membrane endothelial keratoplasty combined with phacoemulsification and
      intraocular lens implantation: advanced triple procedure.
AB  - PURPOSE: To evaluate the functional and morphologic outcome of Descemet membrane
      endothelial keratoplasty (DMEK) combined with phacoemulsification and intraocular
      lens implantation in patients suffering from endothelial dysfunction and
      cataract. DESIGN: Retrospective, single-center, consecutive case series. METHODS:
      Triple-DMEK (DMEK with simultaneous cataract surgery) was performed in 61
      consecutive eyes of 56 patients using corneal donor tissue pre-stored in either
      short-term culture (Optisol-GS) at 4 C or organ culture (Dulbecco's modified
      Eagle's medium, CorneaMax medium) at 34 C. Main outcome measures included the
      number of air injections necessary for graft attachment as well as best-corrected
      visual acuity (BCVA [logMAR]), central corneal thickness (CCT), endothelial cell
      density (ECD), refractive spherical equivalent, refractive cylinder, and
      topographic cylinder at 1, 3, and 6 months postoperatively. RESULTS: BCVA
      increased from 0.6 +/- 0.23 logMAR preoperatively (n = 54) to 0.19 +/- 0.22
      logMAR at 6 months (n = 27) after surgery (P <= .05). ECD of donor corneas
      decreased from 2573 +/- 235 cells/mm(2) (n = 61) to 1550 +/- 326 cells/mm(2) (n =
      29) after 6 months (P <= .05). CCT decreased from 651 +/- 69 MUm (n = 54)
      preoperatively to 521 +/- 65 MUm (n = 27) after 6 months (P <= .05). Refractive
      spherical equivalent was -0.3 +/- 2.8 D (n = 27) preoperatively and 0.9 +/- 1.5 D
      6 months (n = 27) after surgery. A total of 54.5% of eyes were within 1 D of
      emmetropia (n = 12) and 77.3% were within 2 D of emmetropia (n = 17) 6 months (n
      = 22) after surgery. Refractive cylinder was -0.9 +/- 1.0 D preoperatively (n =
      49) and -1.5 +/- 1.0 D 6 months (n = 23) after surgery. The change in refractive
      cylinder within the first month was statistically significant (P <= .05; Wilcoxon
      test). Topographic cylinder was 2.1 +/- 1.7 D preoperatively (n = 58) and 1.7 +/-
      1.1 D 6 months (n = 28) after surgery. Between 3 and 6 months a significant
      change in topographic cylinder towards lower values was measured (P <= 0.05;
      Wilcoxon test). Optimized spherical results were achieved by selecting
      intraocular lenses based on a hyperopic shift of -0.75 D. CONCLUSION: DMEK
      combined with cataract surgery (triple procedure) can routinely be performed in
      cases of endothelial dystrophy and cataract. The addition of cataract surgery to
      DMEK had no adverse effect on endothelial function or graft adhesion and did not
      increase the likelihood of postoperative complications.

PMID- 22465364
TI  - Subconjunctival sirolimus for the treatment of chronic active anterior uveitis:
      results of a pilot trial.
AB  - PURPOSE: To evaluate the safety and possible efficacy of subconjunctival
      sirolimus for the treatment of chronic active anterior uveitis. DESIGN:
      Prospective, nonrandomized, open-label clinical trial. METHODS: This single
      center pilot trial enrolled 5 patients with chronic active anterior uveitis. The
      study drug was administered as a single subconjunctival injection of 30 MUL (1320
      MUg) sirolimus in the study eye at the baseline visit. Study visits were
      performed at baseline, at 2 weeks, at 4 weeks, and monthly until 4 months, and
      included a complete ophthalmic examination, review of systems, adverse event
      assessment at each visit, physical examination, and ancillary ophthalmic testing
      at some visits. The primary outcome measure was a 2-step reduction in the
      anterior chamber inflammation within 4 weeks of injection of the study drug.
      RESULTS: There were 3 female and 2 male patients; 4 patients had idiopathic
      anterior uveitis and 1 had psoriatic arthritis-associated anterior uveitis. Three
      of the 5 patients met the primary outcome criteria by showing at least a 2-step
      decrease in inflammation within 4 weeks; 2 patients showed a 1-step decrease in
      inflammation within the same time frame. No recurrence was encountered during a 4
      month follow-up. There were no serious adverse events. CONCLUSIONS:
      Subconjunctival sirolimus appears to be well tolerated in this pilot trial and
      shows promise as a treatment for active inflammation in patients with chronic
      anterior uveitis. Larger studies are needed to assess its usefulness in uveitis.

PMID- 22465366
TI  - One-year results of three monthly ranibizumab injections and as-needed
      reinjections for polypoidal choroidal vasculopathy in Japanese patients.
AB  - PURPOSE: To investigate the 1-year outcomes of monthly intravitreal injections of
      ranibizumab for 3 months followed by an as-needed reinjection schedule to treat
      polypoidal choroidal vasculopathy (PCV) in Japanese patients. DESIGN:
      Prospective, consecutive case series. METHODS: Eighty-five eyes of 82 consecutive
      Japanese patients with naive symptomatic PCV received monthly intravitreal
      injections of ranibizumab for 3 months followed by an as-needed reinjection
      schedule. Eighty-one eyes (95%) followed for 1 year were studied. RESULTS: A mean
      of 4.2 +/- 1.3 (mean +/- standard deviation) injections were administered over 1
      year. Twenty-three of 81 eyes (28%) did not require additional injections and 32
      eyes (40%) required only 1 injection after the 3 monthly injections. The mean (+/
      standard error) logarithm of minimal angle of resolution (logMAR) visual acuity
      (VA) at baseline was 0.59 +/- 0.37 and improved to 0.37 +/- 0.30 (P = .001).
      Thirty eyes (37%) and 5 eyes (6%), respectively, had improved and decreased VA of
      0.3 or more logMAR unit. Indocyanine green angiography showed that the polypoidal
      lesions resolved in 21 eyes (26%) and 32 eyes (40%) 3 months and 1 year after the
      first injection, respectively. Abnormal choroidal vessels remained in all eyes.
      CONCLUSIONS: Monthly injections of ranibizumab for 3 months to treat PCV improved
      the VA, and a reinjection schedule based on need maintained the improved VA. The
      polypoidal lesions tended to improve over 1 year, whereas abnormal choroidal
      vessels remained in all eyes. Further long-term follow-up is needed to determine
      the efficacy of ranibizumab therapy for PCV.

PMID- 22465367
TI  - Determinants of lens vault and association with narrow angles in patients from
      Singapore.
AB  - PURPOSE: To describe the distribution and determinants of lens vault and to
      investigate the association of lens vault with narrow angles. DESIGN: Prospective
      cross-sectional study. METHODS: Phakic subjects 50 years and older were evaluated
      at a primary healthcare clinic with gonioscopy, partial laser interferometry, and
      anterior segment optical coherence tomography (AS-OCT). Narrow angles were
      defined as posterior trabecular meshwork not visible for >=2 quadrants on non
      indentation gonioscopy. Lens vault was defined as the perpendicular distance
      between the anterior pole of the crystalline lens and the horizontal line joining
      the 2 scleral spurs on horizontal AS-OCT scans. Analysis of covariance,
      multivariate logistic regression, and area under the receiver operating
      characteristic curves (AUC) were performed. RESULTS: Of the 2047 subjects
      recruited, 582 were excluded because of poor image quality or inability to locate
      scleral spurs, leaving 1465 subjects for analysis. Eyes with narrow angles had
      greater lens vault compared to eyes with open angles (775.6 um vs 386.5 um, P <
      .0001). Women had significantly greater lens vault than men (497.28 um vs 438.56
      um, P < .001), and lens vault increased significantly with age (P for trend
      <.001). Adjusted for age and sex, significant associations with greater lens
      vault were shorter axial length, shallower anterior chamber depth(ACD), higher
      intraocular pressure, and more hyperopic spherical equivalent (all P < .001). On
      multivariate analysis, subjects with lens vault >667.6 um were more likely to
      have narrow angles (OR 2.201, 95% CI: 1.070-4.526) compared to those with lens
      vault <=462.7 um. The AUC for lens vault (0.816) and ACD (0.822) for detecting
      narrow angles were similar (P = .582). CONCLUSIONS: Lens vault was independently
      associated with narrow angles and may be useful in screening to detect eyes with
      narrow angles.

PMID- 22465368
TI  - Factors associated with the response of age-related macular degeneration to
      intravitreal ranibizumab treatment.
AB  - PURPOSE: To investigate factors affecting patient response to intravitreal
      ranibizumab treatment for age-related macular degeneration (AMD). DESIGN:
      Retrospective chart review. METHODS: We reviewed medical records of 105
      consecutive eyes with AMD treated with intravitreal ranibizumab injections and
      followed for more than 1 year after treatment. Response to ranibizumab treatment
      was compared between typical neovascular AMD and polypoidal choroidal
      vasculopathy (PCV). Furthermore, we investigated associations of age, lesion
      size, and single nucleotide polymorphisms (SNPs) in CFH and ARMS2 genes with
      treatment response. RESULTS: Forty-nine eyes were diagnosed with typical
      neovascular AMD and 56 eyes with PCV. Serous retinal detachment and retinal edema
      resolved similarly in both typical neovascular AMD and PCV after treatment.
      However, visual acuity (VA) significantly improved in eyes with PCV, whereas VA
      was maintained in typical neovascular AMD. At the third and twelfth months after
      injection, VA was better in PCV than in typical neovascular AMD (P = .027 and P =
      .044, respectively), although there were no differences in baseline VA between
      the 2 groups. Age and size of greatest linear dimension were significantly
      associated with visual prognosis in typical neovascular AMD but not in PCV. There
      was no clear association between 3 SNPs and responsiveness to ranibizumab
      treatment. CONCLUSIONS: Although exudative changes were equivalent following
      ranibizumab treatment in both typical neovascular AMD and PCV, there was a
      significant increase in VA in PCV compared to typical neovascular AMD. Age and
      greatest linear dimension correlated with visual prognosis only in typical
      neovascular AMD and not in PCV.

PMID- 22465369
TI  - Surgery for psychiatric disorders.
AB  - Surgery in psychiatric disorders has a long history and has regained momentum in
      the past few decades with deep brain stimulation (DBS). DBS is an adjustable and
      reversible neurosurgical intervention using implanted electrodes to deliver
      controlled electrical pulses to targeted areas of the brain. It holds great
      promise for therapy-refractory obsessive-compulsive disorder. Several double
      blind controlled and open trials have been conducted and the response rate is
      estimated around 54%. Open trials have shown encouraging results with DBS for
      therapy-refractory depression and case reports have shown potential effects of
      DBS on addiction. Another promising indication is Tourette syndrome, where
      potential efficacy of DBS is shown by several case series and a few controlled
      trials. Further research should focus on optimizing DBS with respect to target
      location and increasing the number of controlled double-blinded trials. In
      addition, new indications for DBS and new target options should be explored in
      preclinical research. 

PMID- 22465370
TI  - Evolution and rebirth of functional stereotaxy in the subthalamus.
AB  - The first human stereotactic surgery based on intracerebral landmarks and
      Cartesian coordinates was performed in 1947. With this followed the publication
      of a number of stereotactic frames and atlases. The intercommissural line joining
      the anterior and posterior commissures was to define stereotactic coordinate
      systems used in movement disorders and other functional neurosurgical procedures.
      Initially the target for Parkinson disease was the globus pallidus internus
      (GPi), but many investigators soon turned to the thalamus or parts of the
      subthalamus, but not the subthalamic nucleus. Microelectrode recording was
      introduced in 1961. With the apparent clinical efficacy of L-DOPA in 1965
      interest in stereotactic surgery for Parkinson disease declined. The failure of
      prolonged, consistent pharmacologic management of bradykinesia and tremor, the
      side effects of dyskinesias, and the fading therapeutic success of medical
      treatment of movement disorders led to a resurgence of interest in the surgical
      management of movement disorders. With advances in understanding of the
      functional anatomy of the corticobasal ganglia circuit, advances in brain
      imaging, more sophisticated electrophysiologic recordings, and the use of deep
      brain stimulation as a reversible lesion, stereotactic surgery returned as a
      viable option for the treatment of movement disorders. The posterior medial part
      of the globus pallidus, ventral intermediate nucleus of the thalamus, and the
      subthalamus, its nuclei and pathways, are sites for interrupting pathophysiologic
      circuits. Not only has this been applied to movement disorders, but to epilepsy,
      chronic pain, and behavioral disorders. 

PMID- 22465371
TI  - An anatomic study of the occipital transtentorial keyhole approach.
AB  - OBJECTIVE: To provide an anatomic basis of the occipital transtentorial keyhole
      approach (OTKA), then explore its feasibility and surgical indication. METHODS:
      Eight cadaveric heads were prepared for this anatomic study. A longitudinal
      linear 4-cm skin incision that begun at the upper margin of the transverse sinus,
      1.5 cm away from the superior sagittal sinus. This was designed for the OTKA. The
      keyhole craniotomy and conventional craniotomy were performed sequentially for
      observation and measurement. RESULTS: The interhemispheric corridor and the
      supratentorial corridor can be used in the OTKA. The surgical field extended
      superior to the splenium, inferior to the superior medullary velum, ipsilateral
      to the middle and posterior parts of the medial and inferior temporal lobe,
      contralateral to the pulvinar, and anterior to the massa intermedia in the third
      ventricle. The exposure area of the OTKA was 72.05 +/- 6.26 mm(2) and 182.97 +/-
      14.65 mm(2) before and after the tentorial incision, respectively. The exposure
      area of the conventional craniotomy was 187.28 +/- 20.16 mm(2), which had no
      significant difference to the OTKA. The working angles of the five target points
      were all smaller for the OTKA than for the conventional approach. The depth of
      the posterior third ventricle that could be observed was 14.70 +/- 2.54 mm with
      the OTKA. CONCLUSIONS: Compared with the conventional approach, the OTKA is a
      more minimally invasive surgical procedure for treatment of the lesions in the
      pineal region and the middle and posterior parts of the medial and inferior
      temporal lobe. However, the working angles are relatively narrow.

PMID- 22465372
TI  - Outcomes for clip ligation and hematoma evacuation associated with 102 patients
      with ruptured middle cerebral artery aneurysms.
AB  - OBJECTIVE: Few studies have investigated the implications of intracerebral
      hematoma (ICH) due to rupture of a middle cerebral artery (MCA) aneurysm and
      patient outcomes. We hypothesized that patients with Hunt-Hess (HH) grade IV-V
      may not benefit from aggressive measures. METHODS: A prospectively acquired
      aneurysm database was examined. We found 144 patients who harbored a ruptured MCA
      aneurysm and suffered from ICH or intrasylvian hematoma with or without
      subarachnoid hemorrhage. The mean age of our patients was 52.5 years (range, 10
      82 years) with 87 women and 57 men. Of these, 122 (84.7%) underwent a combination
      of interventions, including clip ligation, hematoma evacuation, and/or
      endosaccular coiling; most patients underwent clip ligation at the same time as
      their hematoma was evacuated. The discharge information was not available for two
      patients. We examined significant associations among presenting details (e.g.,
      age, sex, admission HH grade) and patients' final outcome. RESULTS: The total in
      hospital mortality rate was 49% (70 of 142 patients); 42% (51 of 120) for the
      patients who underwent an intervention and 86.4% (19 of 22) for those who did not
      undergo any intervention. Among our patients, approximately 52% with an admission
      HH grade of IV/V died in-hospital after surgery, whereas 21% with admission HH
      grade of I-III expired during the same time. In the patient cohort with
      presenting with HH grade IV and V, 4% (3 of 76) demonstrated Glasgow outcome
      scale 4-5 at discharge, whereas 15% (12 of 78) displayed Glasgow outcome scale 4
      5 at 6-month follow-up. Age and sex did not affect outcome. CONCLUSIONS:
      Aggressive clip ligation and hematoma evacuation remains a reasonable option for
      patients suffering from an ICH associated with a ruptured MCA aneurysm. Admission
      HH grade is the primary prognostic factor for outcome among this patient
      population as more than half of patients with HH grade IV and V expired during
      their hospitalization despite aggressive treatment of their hematoma and
      aneurysm. Long-term functional outcome was poor in up to 85% of surviving
      patients with HH grade IV-V. It may be beneficial to discuss these prognostic
      factors with the family before implementing aggressive measures.

PMID- 22465374
TI  - Mutations in vacuolar H+ -ATPase subunits lead to biliary developmental defects
      in zebrafish.
AB  - We identified three zebrafish mutants with defects in biliary development. One of
      these mutants, pekin (pn), also demonstrated generalized hypopigmentation and
      other defects, including disruption of retinal cell layers, lack of zymogen
      granules in the pancreas, and dilated Golgi in intestinal epithelial cells. Bile
      duct cells in pn demonstrated an accumulation of electron dense bodies. We
      determined that the causative defect in pn was a splice site mutation in the
      atp6ap2 gene that leads to an inframe stop codon. atp6ap2 encodes a subunit of
      the vacuolar H(+)-ATPase (V-H(+)-ATPase), which modulates pH in intracellular
      compartments. The Atp6ap2 subunit has also been shown to function as an
      intracellular renin receptor that stimulates fibrogenesis. Here we show that
      mutants and morphants involving other V-H(+)-ATPase subunits also demonstrated
      developmental biliary defects, but did not demonstrate the inhibition of
      fibrogenic genes observed in pn. The defects in pn are reminiscent of those we
      and others have observed in class C VPS (vacuolar protein sorting) family mutants
      and morphants, and we report here that knockdown of atp6ap2 and vps33b had an
      additive negative effect on biliary development. Our findings suggest that
      pathways which are important in modulating intracompartmental pH lead to defects
      in digestive organ development, and support previous studies demonstrating the
      importance of intracellular sorting pathways in biliary development.

PMID- 22465375
TI  - Life goal appraisal and marijuana use among college students.
AB  - The current study was designed to examine the motivational context of marijuana
      use among college students using idiographic and nomothetic goal assessment
      approaches. One hundred and ninety-eight introductory psychology students
      completed a questionnaire that included measures of life goals and marijuana use
      behavior. Forty-three percent of students surveyed reported the use of marijuana
      in the past 90 days. Students rated a set of five personally salient, self
      generated and five normative life goals on a series of dimensions using the
      personal projects methodology (Little, 1983). Goal meaning and goal efficacy
      ratings for each type of assessment were studied in relation to the likelihood of
      marijuana use and the frequency of use among current users. Logistic regression
      analyses showed that levels of meaning for self-generated life goals and
      normative academic life goals were independent predictors of whether students
      used marijuana in the past 90 days. Students who reported high levels of meaning
      were less likely to have used marijuana in the past 90 days. For students who
      used marijuana, higher meaning ratings related to involvement in
      groups/organizations and fitness were correlated with decreased frequency of use.
      Moreover, ratings of efficacy related to self-generated goals were associated
      with less frequent use among smokers. These results suggest that meaning related
      to life goal pursuit may be associated with students' decisions to use marijuana.
      Potential implications for interventions are discussed.

PMID- 22465373
TI  - Specification of neural crest into sensory neuron and melanocyte lineages.
AB  - Elucidating the mechanisms by which multipotent cells differentiate into distinct
      lineages is a common theme underlying developmental biology investigations.
      Progress has been made in understanding some of the essential factors and
      pathways involved in the specification of different lineages from the neural
      crest. These include gene regulatory networks involving transcription factor
      hierarchies and input from signaling pathways mediated from environmental cues.
      In this review, we examine the mechanisms for two lineages that are derived from
      the neural crest, peripheral sensory neurons and melanocytes. Insights into the
      specification of these cell types may reveal common themes in the specification
      processes that occur throughout development.

PMID- 22465376
TI  - Psychophysiological reactivity to environmental tobacco smoke on smokers and non
      smokers.
AB  - Environmental tobacco smoke (ETS) is an air pollutant with a relevant impact on
      public health. In addition, ETS is a significant stimulus that may elicit
      different responses depending on previous experience and current status regarding
      smoking. Exposure to cigarette cues has been shown to be a reliable method for
      inducing subjective and physiological responses. However, the role of ETS as a
      stimulus has not received, to date, enough attention in the research literature.
      This study aimed to analyse both the autonomic and subjective responses of
      smokers and non-smokers to exposure to ETS. To that end, 41 non-smokers and 57
      smokers were exposed to ETS, in a controlled laboratory setting. We measured the
      subjective perception of smoke, unpleasantness, heart rate and skin conductance
      to compare the reactions of smokers and non-smokers to ETS. Additionally,
      subjective tobacco craving after exposure was assessed for current smokers. We
      found different psychophysiological responses to ETS exposure for smokers and non
      smokers. Smokers showed a generalised increase in autonomic activity,
      significantly greater than that of non-smokers. In addition, heart rate increase
      during exposure to ETS was positively correlated with subjective craving. Our
      data suggested that ETS was an important stimulus and acted as a relevant cue for
      smokers; it induced both psychophysiological reactions and subjective craving.
      Hence, this kind of stimulus within the cue-reactivity research paradigm may be
      useful for studying the effect of ETS on smokers' reactions, craving, quitting
      attempts, or relapse probabilities.

PMID- 22465377
TI  - Social disorder, APOE-E4 genotype, and change in cognitive function among older
      adults living in Chicago.
AB  - The goal of this paper is to describe the simultaneous influence of social and
      genetic risk factors on declines in cognitive functioning among older American
      adults. We use detailed information about the social characteristics of older
      adults' neighborhoods from the Chicago Health and Aging Project (n = 1655; ages
      65+) in conjunction with information about respondent's APOE genotype to predict
      changes in cognitive function over time. Results indicate that the presence of
      the epsilon4 allele is associated with a significantly lower cognitive function
      score at baseline and greater declines in cognitive function compared to those
      without this risk allele. Importantly, we also show significant variation in the
      effect of the epsilon4 allele across neighborhoods and our results indicate that
      this genotype is more strongly associated with cognitive function for residents
      of neighborhoods with the lowest levels of social disorder. Our findings support
      the non-causal social push gene-environment interaction model.

PMID- 22465378
TI  - Whiners, deniers, and self-rated health: what are the implications for measuring
      health inequalities? A commentary on Layes, et al.

PMID- 22465379
TI  - OxyContin(r) as currency: OxyContin(r) use and increased social capital among
      rural Appalachian drug users.
AB  - Studies have shown that position within networks of social relations can have
      direct implications on the health behaviors of individuals. The present study
      examines connections between drug use and individual social capital within social
      networks of drug users (n = 503) from rural Appalachian Kentucky, U.S.A.
      Respondent driven sampling was used to recruit individuals age 18 and older who
      had used one of the following drugs to get high: cocaine, crack, heroin,
      methamphetamine, or prescription opioids. Substance use was measured via self
      report and social network analysis of participants' drug use network was used to
      compute effective size, a measure of social capital. Drug network ties were based
      on sociometric data on recent (past 6 month) drug co-usage. Multivariate multi
      level ordinal regression was used to model the independent effect of socio
      demographic and drug use characteristics on social capital. Adjusting for gender,
      income, and education, daily OxyContin((r)) use was found to be significantly
      associated with greater social capital, and daily marijuana use was associated
      with less social capital. These results suggest that in regions with marked
      economic disparities such as rural Appalachia, OxyContin((r)) may serve as a form
      of currency that is associated with increased social capital among drug users.
      Interventions focusing on increasing alternate pathways to acquiring social
      capital may be one way in which to alleviate the burden of drug use in this high
      risk population.

PMID- 22465380
TI  - Healthy travel and the socio-economic structure of car commuting in Cambridge,
      UK: a mixed-methods analysis.
AB  - Car use is associated with substantial health and environmental costs but
      research in deprived populations indicates that car access may also promote
      psychosocial well-being within car-oriented environments. This mixed-method
      (quantitative and qualitative) study examined this issue in a more affluent
      setting, investigating the socio-economic structure of car commuting in
      Cambridge, UK. Our analyses involved integrating self-reported questionnaire data
      from 1142 participants in the Commuting and Health in Cambridge study (collected
      in 2009) and in-depth interviews with 50 participants (collected 2009-2010). Even
      in Britain's leading 'cycling city', cars were a key resource in bridging the gap
      between individuals' desires and their circumstances. This applied both to long
      term life goals such as home ownership and to shorter-term challenges such as
      illness. Yet car commuting was also subject to constraints, with rush hour
      traffic pushing drivers to start work earlier and with restrictions on, or
      charges for, workplace parking pushing drivers towards multimodal journeys (e.g.
      driving to a 'park-and-ride' site then walking). These patterns of car commuting
      were socio-economically structured in several ways. First, the gradient of
      housing costs made living near Cambridge more expensive, affecting who could
      'afford' to cycle and perhaps making cycling the more salient local marker of
      Bourdieu's class distinction. Nevertheless, cars were generally affordable in
      this relatively affluent, highly-educated population, reducing the barrier which
      distance posed to labour-force participation. Finally, having the option of
      starting work early required flexible hours, a form of job control which in
      Britain is more common among higher occupational classes. Following a social
      model of disability, we conclude that socio-economic advantage can make car
      oriented environments less disabling via both greater affluence and greater job
      control, and in ways manifested across the full socio-economic range. This
      suggests the importance of combining individual-level 'healthy travel'
      interventions with measures aimed at creating travel environments in which all
      social groups can pursue healthy and satisfying lives.

PMID- 22465381
TI  - Family functioning as a mediator between neighborhood conditions and children's
      health: evidence from a national survey in the United States.
AB  - This study examines whether the associations between neighborhood conditions and
      children's health can be indirect and operate through aspects of family
      functioning. We use data from the 2007 National Survey of Children's Health in
      the United States with the interviewed parents/guardians as the only source of
      the data. Our study sample includes 53,023 children aged between 6 and 17 years.
      Using structural equation modeling, we test both direct and indirect
      relationships between a family functioning index, a general indicator of
      children's health status, and three neighborhood factors: neighborhood physical
      resources, environmental threats, and collective efficacy. Covariates in the
      analysis include gender, age, income, race, family structure, parental education,
      and health insurance coverage. All the three neighborhood factors show direct
      associations with children's general health status, as well as indirect
      associations mediated by aspects of family functioning. Among the three
      neighborhood factors, collective efficacy and environmental threats are found to
      have much stronger associations with children's general health than physical
      resources. When designing health-promoting neighborhoods for children and
      families, it may be more efficient for urban planners and health professionals to
      focus on community programs that reduce environmental stressors and foster
      neighborhood cohesion than programs that solely improve physical infrastructure.
      This study also verifies that aspects of family functioning mediate the
      associations between neighborhood conditions and children's health. It is
      recommended that both family and neighborhood are critical points for child
      health intervention.

PMID- 22465382
TI  - The length of unemployment predicts mortality, differently in men and women, and
      by cause of death: a six year mortality follow-up of the Swedish 1992-1996
      recession.
AB  - This study examines the relationship between the total amount of accumulated
      unemployment during the deep Swedish recession of 1992-1996 and mortality in the
      following 6 years. Nearly 3.4 million Swedish men and women, born between 1931
      and 1965 who were gainfully employed at the time of the 1990 census were
      included. Almost 23% of these individuals were unemployed at some point during
      the recession. We conduct a prospective cohort study utilizing Cox proportional
      hazard regression with a mortality follow-up from January 1997 to December 2002.
      We adjust for health status (1982-1991), baseline (1991) social, family, and
      employer characteristics of individuals before the recession. The findings
      suggest that long-term unemployment is related to elevated all-cause mortality
      for men and women. The excess mortality effects were small for women and
      attributable to a positive, linear increase in the hazard of alcohol disease
      related mortality and external causes-of-death not classified as suicides or
      transport accidents. For men, the excess hazard of all-cause mortality was best
      represented by a cubic, non-linear shape. The predicted hazard increases rapidly
      with the shortest and longest accumulated levels of unemployment. However, the
      underlying pattern differed by cause-of-death. The cancer, circulatory, and
      alcohol disease-related analyses suggest that mortality peaks with mid-levels of
      accumulated unemployment and then declines with longer duration unemployment. For
      men, we observed a positive, linear increase in the hazard ratios associated with
      transport and suicide mortality, and a very steep non-linear increase in the
      excess hazard ratio associated with other external causes of death that were not
      classified as suicide or transport accidents. In conclusion, mortality risk
      increases with the duration of unemployment among men and women. This was best
      described by a cubic function for men and a linear function for women. Behind
      this pattern, different causes-of-death varied in their relation to the
      accumulation of unemployment.

PMID- 22465383
TI  - Trust, self-rated health and mortality: a longitudinal study among ageing people
      in Southern Finland.
AB  - Poor self-rated health (SRH) predicts mortality significantly. High trust has
      been shown to associate with better SRH in cross-sectional studies and survival
      in longitudinal studies. However, little is known about the associations between
      trust, SRH and mortality among ageing people. The present study examined whether
      low trust at the baseline predicted higher all-cause mortality in a follow-up of
      over five years among ageing people, and whether the trust to mortality
      relationship varied by SRH. The study used longitudinal, questionnaire-based
      survey data gathered in 2002 (n = 2815; 66%) among three age cohorts (born in
      1926-30, 1936-40 and 1946-50) living in the Lahti region, Southern Finland. Two
      survey follow-ups were done, the first in 2005 (n = 2476, 60%) and the second in
      2008 (n = 2064, 73%). Deaths during the follow-up were obtained from the covering
      National Population Registry. Those who died within the first one year of follow
      up were excluded from the analyses to reduce potential bias due to early deaths.
      Cox proportional hazard models were used to derive the results. Mortality proved
      to be higher among men with low trust, even if their SRH had been good at the
      baseline. Among women, no significant associations were found. The risk
      attenuated after adjustment for background health-related covariates, but the
      gradient remained statistically significant in all models. Initial SRH did not
      substantially explain the gradient of trust in mortality among men. Moreover, a
      Sobel test of indirect effects showed that SRH had no significant mediating role
      in links between trust and mortality. Thus, low trust is a sensitive indicator of
      higher mortality risk among ageing men.

PMID- 22465384
TI  - Quercetin attenuates airway inflammation and mucus production induced by
      cigarette smoke in rats.
AB  - Mucus hypersecretion is a feature of many chronic airway diseases induced by
      cigarette smoke (CS), and evidence suggests that the antioxidant and anti
      inflammatory flavonoid quercetin may protect against CS-induced respiratory
      pathology. In this study, the ability of quercetin to protect against CS-induced
      mucin expression was examined in vivo and in vitro. Quercetin or 0.2% Tween
      aqueous solution was administered intraperitoneally to rats,which were then
      exposed to CS for 28 days. Cell counts and pro-inflammatory cytokine levels were
      measured in bronchoalveolar lavage fluid (BALF). Lung tissue was examined for
      total glutathione (GSH) and total antioxidant capacity (T-AOC), histopathological
      lesions, goblet cell hyperplasia, epidermal growth factor receptor (EGFR)
      phosphorylation and NF-kappaB pathway activation. To complement these in vitro
      studies, human airway epithelial NCI-H292 cells were pretreated with quercetin
      and then exposed to cigarette smoke extract (CSE). Cell lysates were examined for
      Muc5ac expression, EGFR phosphorylation and NF-kappaB pathway activation. In
      vivo, quercetin pretreatment suppressed CS-induced goblet cell hyperplasia,
      inflammation, oxidative stress, EGFR phosphorylation and NF-kappaB pathway
      activation in rat lung. In vitro, quercetin pretreatment attenuated the CSE
      induced Muc5ac expression, NF-kappaB activation and EGFR phosphorylation. Our
      results suggest that quercetin attenuates CS-induced mucin protein synthesis in
      rat lung, possibly by inhibiting oxidative stress and inflammation via a
      mechanism involving NF-kappaB pathway activation and EGFR phosphorylation. These
      findings suggest that quercetin has a potential for treating chronic airway
      diseases.

PMID- 22465385
TI  - Cryopreservation of adenovirus-transfected dendritic cells (DCs) for clinical
      use.
AB  - In this study, we examined the effects of cryoprotectant, freezing and thawing,
      and adenovirus (Adv) transduction on the viability, transgene expression,
      phenotype, and function of human dendritic cells (DCs). DCs were differentiated
      from cultured peripheral blood (PB) monocytes following Elutra isolation using
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL
      4) for 6 days and then transduced using an Adv vector with an IL-12 transgene.
      Fresh, cryopreserved, and thawed transduced immature DCs were examined for their:
      1) cellular concentration and viability; 2) antigenicity using an allogeneic
      mixed lymphocyte reaction (MLR); 3) phenotype (HLA-DR and CD11c) and activation
      (CD83); and 4) transgene expression based on IL-12 secretion. Stability studies
      revealed that transduced DCs could be held in cryoprotectant for as long as 75
      min at 2-8 degrees C prior to freezing with little effect on their viability and
      cellularity. Further, cryopreservation, storage, and thawing reduced the
      viability of the transduced DCs by an average of 7.7%; and had no significant
      impact on DC phenotype and activation. In summary, cryopreservation, storage, and
      thawing had no significant effect on DC viability, function, and transgene
      expression by Adv-transduced DCs.

PMID- 22465386
TI  - Nasal immunization with different forms of heat shock protein-65 reduced high
      cholesterol-diet-driven rabbit atherosclerosis.
AB  - Heat shock protein-65 (Hsp65) is an important pro-atherogenic factor, but nasal
      immunization of Hsp65 can induce immune tolerance and reduce atherosclerotic
      inflammation. Here, we describe the effects of different forms of Hsp65 antigen
      inoculated, i.e. Hsp65 DNA, Hsp65 protein, Hsp65 DNA prime combined with Hsp65
      protein boost, on high-cholesterol-diet-driven rabbit atherosclerosis lesions.
      The results showed that sera anti-Hsp65 IgG antibodies were lower induced and
      protective anti-Hsp65 IgA in nasal cavity and lung were induced after rabbits
      were immunized with different forms of Hsp65. However, the avidity between Hsp65
      IgG antibody and antigen is different. Hsp65 DNA prime-protein boost could
      further improve the avidity compared with Hsp65 DNA immunization alone, but only
      immunization with Hsp65 protein alone obtain the best avidity. In addition, more
      protective IL-10 and less adverse IFN-gamma were produced and sera TC and LDL-C
      were decreased obviously at different extents in immunized groups. As a result,
      atherosclerosis lesions were significantly attenuated, but only nasal
      immunization with Hsp65 protein alone may be the best effective form of Hsp65
      antigen to control atherosclerotic lesions. The results demonstrated that
      different forms of Hsp65 antigen could produce different effects in the treatment
      of atherosclerosis. Immunization mucosally with Hsp65 protein could be a
      promising therapeutic method for atherosclerosis.

PMID- 22465387
TI  - [Positional cranial deformations: a clinical-epidemiological study].
AB  - INTRODUCTION: Cranial deformities have always existed, but it is only until
      recently that they provoked a greater interest. Several reports have demonstrated
      an increasing tendency for occipital plagiocephaly. This work presents an
      analysis of the clinical-epidemiological features of these deformities in our
      area. PATIENTS AND METHODS: The medical records and neuroimaging studies of 158
      children seen at our hospital due to a skull deformation were analyzed, paying
      special attention to risk factors. RESULTS: During the study period, an increase
      in the number of consultations for skull deformation of children was noted. The
      mean age for the patients at consultation was 9 months. There was a predominance
      of boys (68%) over girls. The deformities were: unilateral- (89.2%) or bilateral
      posterior plagiocephaly (7.6%), and dolicochephaly (3.2%). In addition to the
      supine position for sleeping, there were several risk factors, among them
      pericerebral collections of cerebrospinal fluid found in 50% of children
      subjected to neuroimaging studies. Most children were managed conservatively,
      while 12 patients were given helmets, which led to an improvement in 136 cases.
      DISCUSSION AND CONCLUSIONS: The present findings agree with those in the current
      literature. A unique result of this study was the high rate of pericerebral fluid
      collections found in children assessed with neuroimaging methods. The increase in
      positional plagiocephaly seems to parallel the application of the recommendations
      for supine sleeping position established by the American Academy of Pediatrics
      for preventing the sudden infant death syndrome. The role played by Pediatricians
      in the detection, initial management and referral of these children is
      highlighted. Prevention measures seem to be more important than those regarding
      treatment.

PMID- 22465388
TI  - [Neuropsychological difficulties in adopted children from Russia: aetiological
      considerations].

PMID- 22465390
TI  - Public-private partnerships in translational medicine: concepts and practical
      examples.
AB  - The way forward in multidisciplinary research according to former NIH's director
      Elias Zerhouni is to engage in predictive, personalized, preemptive and
      participatory medicine. For the creation of the optimal innovation climate that
      would allow for such a strategy, public-private partnerships have been widely
      proposed as an important instrument. Public-private partnerships have become an
      important instrument to expedite translational research in medicine. The
      Netherlands have initiated three large public-private partnerships in the life
      sciences and health area to facilitate the translation of valuable basic
      scientific concepts to new products and services in medicine. The focus of these
      partnerships has been on drug development, improved diagnosis and regenerative
      medicine. The Dutch model of public-private partnership forms the blueprint of a
      much larger European initiative called EATRIS. This paper will provide practical
      examples of public-private partnerships initiated to expedite the translation of
      new technology for drug development towards the clinic. Three specific
      technologies are in focus: companion diagnostics using nuclear medicine, the use
      of ultra high field MRI to generate sensitive surrogate endpoints based on
      endogenous contrast, and MRI guidance for High Intensity Focused Ultrasound
      mediated drug delivery.

PMID- 22465389
TI  - Molecular binding of self-assembling peptide EAK16-II with anticancer agent EPT
      and its implication in cancer cell inhibition.
AB  - The current drug delivery techniques involve encapsulation, targeting and
      controlled release of the drug with various molecules or nanoparticles, but
      rarely has the drug molecular state or form been investigated. It is necessary to
      deliver a drug with a prescribed molecular state in order to maximize drug
      therapeutic effects. Here we present two facile methods to characterize molecular
      states of the anticancer drug ellipticine (EPT) encapsulated in the self
      assembling peptide EAK, and relate the different molecular states of EPT to their
      respective cancer inhibition efficacies. The first method is UV-based, where drug
      loading capacity of a particular molecular state was determined. The experimental
      data corroborated a molecular binding model, where peptide-drug interaction was
      assumed to be electrostatic in nature. The developed model could elucidate a
      unique pH effect on protonated EPT loading capacity. The second method is based
      on fluorescence characteristics of EPT, which could differentiate the two
      molecular states: protonated and crystalline of EPT in situ. The inner filter
      effect was, however, found with this method, presenting an ineluctable obstacle
      in quantitative analysis of fluorescence data. A correction method for the inner
      filter effect was thus developed. With this approach, concentrations of EPT at
      different molecular states in its peptide complex solutions were determined. In
      vitro cytotoxicity assay was applied to evaluate the efficacy of the two
      molecular states of EPT, showing that protonated EPT was more efficient at
      killing cancer cells than crystalline EPT. The molecular binding model and two
      characterization methods for EAK-EPT complexation could be extended to other
      carrier-drug systems.

PMID- 22465391
TI  - In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel
      for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis
      graft stenosis.
AB  - Synthetic arteriovenous (AV) hemodialysis grafts are plagued by hyperplasia
      resulting in occlusion and graft failure yet there are no clinically available
      preventative treatments. Here the delivery and degradation of a sirolimus-laden
      polymer gel were monitored in vivo by magnetic resonance imaging (MRI) and its
      efficacy for inhibiting hyperplasia was evaluated in a porcine model of AV graft
      stenosis. Synthetic grafts were placed between the carotid artery and ipsilateral
      jugular vein of swine. A biodegradable polymer gel loaded with sirolimus
      (2.5mg/mL) was immediately applied perivascularly to the venous anastomosis, and
      reapplied by ultrasound-guided injections at one, two and three weeks. Control
      grafts received neither sirolimus nor polymer. The lumen cross-sectional area at
      the graft-vein anastomosis was assessed in vivo by non-invasive MRI. The
      explanted tissues also underwent histological analysis. A specifically developed
      MRI pulse sequence provided a high contrast-to-noise ratio (CNR) between the
      polymer and surrounding tissue that allowed confirmation of gel location after
      injection. Polymer signal decreased up to 80% at three to four weeks after
      injection, slightly faster than its degradation kinetics in vitro. The MR image
      of the polymer was confirmed by visual assessment at necropsy. On histological
      assessment, the mean hyperplasia surface area of the treated graft was 52% lower
      than that of the control grafts (0.43mm(2) vs. 0.89mm(2); p<0.003), while the
      minimum cross-sectional lumen area, as measured on MRI, was doubled (5.3mm(2) vs
      2.5mm(2); p<0.05). In conclusion, customized MRI allowed non-invasive monitoring
      of the location and degradation of drug delivery polymer gels in vivo.
      Perivascular application of sirolimus-laden polymer yielded a significant
      decrease in hyperplasia development and an increase in lumen area at the venous
      anastomosis of AV grafts.

PMID- 22465392
TI  - Prolonging the expression duration of ultrasound-mediated gene transfection using
      PEI nanoparticles.
AB  - Ultrasound (US) irradiation has been found to facilitate the inward transport of
      genetic materials across cell membranes (sonoporation). However, its transfection
      efficiency is generally low, and the expression duration of transfected gene is
      short. Polyethylenimine (PEI), a cationic polymer, has been shown to aggregate
      plasmid DNA and facilitate its internalization. The purpose of this study is to
      determine whether PEI can also prolong the expression duration after US-mediated
      transfection. A mixture of pCMViLUC and 22-kDa linear PEI was transfected to
      cultured cells or mouse muscle by exposure to 1-MHz pulsed US. The duration of
      expression was assessed periodically following US treatment. As expected, strong
      expression of luciferase could be found 30days after the treatment of DNA-PEI
      complex with US exposure, both in vitro and in vivo. However, without US, only
      very low transfection level could be obtained in vivo. The DNA/PEI complex showed
      protective effect against digestion of DNase I enzymes as compared with groups
      without PEI or to which PEI was added following the mixing of plasmid DNA with
      DNase I. PEI enhanced the US transfection efficiency by increasing both the
      intracellular uptake of plasmid DNA and the percentage of transfected cells. Most
      of the DNA uptake occurred at 3h after US exposure, suggesting that endocytosis
      took place. Moreover, the PEI-facilitated US gene transfection depended on the
      ratio of PEI and DNA (N/P ratio), which was different for in-vitro and in-vivo
      conditions. This system could be applied in future human gene therapies.

PMID- 22465393
TI  - Drug nanocrystals: In vivo performances.
AB  - Over the past few decades, there has been a considerable research interest in
      drug nanocrystal system as a pharmaceutical approach for poorly soluble drugs. At
      the beginning lots of works have been done to study various technologies
      associated with production of drug nanocrystals and their in vitro physical and
      chemical properties, such as morphology, formulation composition, stabilities,
      crystalline structure and enhanced solubility and dissolution velocity. Recently,
      in vivo behaviors of the nanocrystals have been generally studied in animals
      (including human), and the results proved that drug nanocrystals could be used as
      a versatile formulation to alter and improve the pharmacokinetic, pharmacodynamic
      and targeting properties of poorly soluble drugs. In this paper, in vivo
      performances of drug nanocrystals exhibited in animals in different
      administration route were reviewed, and the advantages of drug nanocrystals in
      the aspect of safety, pharmacodynamics, pharmacokinetics and targeting delivery
      were discussed in detail.

PMID- 22465394
TI  - Organotypic cell cultures and two-photon imaging: tools for in vitro and in vivo
      assessment of percutaneous drug delivery and skin toxicity.
AB  - The outermost protective layer of the skin, the stratum corneum, is responsible
      for skin impermeability toward external medications and potentially harmful
      chemicals. Stratum corneum is the target for physical and chemical approaches to
      enhance drug permeation. These approaches are commonly investigated in the field
      of drug delivery, but the drug absorption enhancement is often linked with local
      toxicity. In this review we are discussing two emerging technologies for drug and
      chemical studies in the skin: organotypic cell cultures and non-invasive two
      photon microscopic imaging. Even though several cell culture based 'skin
      equivalents' have been introduced and validated for skin irritation testing, they
      are usually leaky and inadequately characterized in terms of permeation. Rat
      epidermal culture model (ROC) has been thoroughly characterized and it shows
      comparable barrier properties with the human skin thereby being useful in drug
      permeation and toxicity studies. In vitro and in vivo visualizations of permeants
      and skin structures are now feasible due to the rapid development of two-photon
      microscopy that allows improved depth scanning and direct in vivo visualization
      of the permeating compounds and adverse reactions in the skin structures. In
      summary, the new tools in percutaneous drug delivery studies will provide new
      insights to the permeation process and local toxicity. These tools may facilitate
      development of effective and safe transdermal drug delivery methods.

PMID- 22465395
TI  - [Reoperation after orbital decompression for Graves' ophthalmopathy].
AB  - INTRODUCTION: The aim of our study was to report the incidence of complications
      requiring early or late reoperation after bone and fat orbital decompression for
      Graves's ophthalmopathy. PATIENTS AND METHOD: We conducted a retrospective
      bicentric study in the Maxillofacial Surgery Departments of Marseille and Lyon.
      Ninety patients were selected from 2006 to 2010, accounting for 168 orbital
      decompressions. The surgical indication was morphological and functional for all
      patients. Several surgical techniques were used: bone and fat orbital
      decompression by trans-palpebral resection, two or three wall orbital
      decompression, malar valgization. RESULTS: Ten patients were reoperated for 12
      revisions, two patients needed two revisions. There were four early revisions for
      two retro-orbital hematoma, one inadequate orbital decompression with persistent
      posterior compressive optic neuropathy, and one recurrent maxillary sinusitis
      with proptosis. The other eight revisions were carried out later for three cases
      of insufficient correction, four cases of proptosis relapse, and one for
      excessive correction with enophthalmos. All patients had satisfactory
      morphological and functional results despite revision surgery. DISCUSSION: Most
      reoperations are difficult to anticipate and their prevention is based on more or
      less specific recommendations. Patients should be informed of the risks and
      benefits and accept the possibility of reoperation. A systematic
      multidisciplinary consultation would standardize and improve the management of
      these patients, by detecting patients at risk of complications and thus
      reoperation.

PMID- 22465396
TI  - Angiogenesis inhibition for the improvement of photodynamic therapy: the revival
      of a promising idea.
AB  - Photodynamic therapy (PDT) is a minimally invasive form of treatment, which is
      clinically approved for the treatment of angiogenic disorders, including certain
      forms of cancer and neovascular eye diseases. Although the concept of PDT has
      existed for a long time now, it has never made a solid entrance into the clinical
      management of cancer. This is likely due to secondary tissue reactions, such as
      inflammation and neoangiogenesis. The recent development of clinically effective
      angiogenesis inhibitors has lead to the initiation of research on the combination
      of PDT with such angiostatic targeted therapies. Preclinical studies in this
      research field have shown promising results, causing a revival in the field of
      PDT. This review reports on the current research efforts on PDT and vascular
      targeted combination therapies. Different combination strategies with
      angiogenesis inhibition and vascular targeting approaches are discussed. In
      addition, the concept of increasing PDT selectivity by targeted delivery of
      photosensitizers is presented. Furthermore, the current insights on sequencing
      the therapy arms of such combinations will be discussed in light of vascular
      normalization induced by angiogenesis inhibition.

PMID- 22465397
TI  - Direction of CRT waste glass processing: electronics recycling industry
      communication.
AB  - Cathode Ray Tube, CRT, waste glass recycling has plagued glass manufacturers,
      electronics recyclers and electronics waste policy makers for decades because the
      total supply of waste glass exceeds demand, and the formulations of CRT glass are
      ill suited for most reuse options. The solutions are to separate the undesirable
      components (e.g. lead oxide) in the waste and create demand for new products.
      Achieving this is no simple feat, however, as there are many obstacles: limited
      knowledge of waste glass composition; limited automation in the recycling
      process; transportation of recycled material; and a weak and underdeveloped
      market. Thus one of the main goals of this paper is to advise electronic glass
      recyclers on how to best manage a diverse supply of glass waste and successfully
      market to end users. Further, this paper offers future directions for academic
      and industry research. To develop the recommendations offered here, a combination
      of approaches were used: (1) a thorough study of historic trends in CRT glass
      chemistry; (2) bulk glass collection and analysis of cullet from a large-scale
      glass recycler; (3) conversations with industry members and a review of potential
      applications; and (4) evaluation of the economic viability of specific uses for
      recycled CRT glass. If academia and industry can solve these problems (for
      example by creating a database of composition organized by manufacturer and glass
      source) then the reuse of CRT glass can be increased.

PMID- 22465398
TI  - Leaching of heavy metals from solidified waste using Portland cement and zeolite
      as a binder.
AB  - This study investigated the properties of solidified waste using ordinary
      Portland cement (OPC) containing synthesized zeolite (SZ) and natural zeolite
      (NZ) as a binder. Natural and synthesized zeolites were used to partially replace
      the OPC at rates of 0%, 20%, and 40% by weight of the binder. Plating sludge was
      used as contaminated waste to replace the binder at rates of 40%, 50% and 60% by
      weight. A water to binder (w/b) ratio of 0.40 was used for all of the mixtures.
      The setting time and compressive strength of the solidified waste were
      investigated, while the leachability of the heavy metals was determined by TCLP.
      Additionally, XRD, XRF, and SEM were performed to investigate the fracture
      surface, while the pore size distribution was analyzed with MIP. The results
      indicated that the setting time of the binders marginally increased as the amount
      of SZ and NZ increased in the mix. The compressive strengths of the pastes
      containing 20 and 40wt.% of NZ were higher than those containing SZ. The
      compressive strengths at 28 days of the SZ solidified waste mixes were 1.2
      31.1MPa and those of NZ solidified waste mixes were 26.0-62.4MPa as compared to
      72.9MPa of the control mix at the same age. The quality of the solidified waste
      containing zeolites was better than that with OPC alone in terms of the
      effectiveness in reducing the leachability. The concentrations of heavy metals in
      the leachates were within the limits specified by the US EPA. SEM and MIP
      revealed that the replacement of Portland cement by zeolites increased the total
      porosity but decreased the average pore size and resulted in the better
      containment of heavy ions from the solidified waste.

PMID- 22465399
TI  - Sensitivity of A1C to diagnose diabetes is decreased in high-risk older Southeast
      Asians.
AB  - OBJECTIVE: To determine the effect of ageing on the performance of glycosylated
      haemoglobin A1C (A1C) for the diagnosis of diabetes mellitus (DM) in Southeast
      Asians. METHODS: A1C was measured in 511 subjects (mean age of 52.4 years; range
      14-93) undergoing the 75-g oral glucose tolerance test (OGTT). Using receiver
      operating curve (ROC) analysis, the performance of A1C for the diagnosis of
      diabetes (using different standard criteria) was compared between 4 groups: <45
      (n=156), 45-54 (n=132), 55-64 (n=122), >=65 years (n=101). RESULTS: Subjects aged
      >=65 years had the highest false-negative rates with fasting plasma glucose
      (60.8%) and A1C (35.1%), the smallest area under ROC curve (0.723, 95% CI 0.627
      0.820), the lowest sensitivity (58.7%, 95% CI 50.4-65.7) and specificity (71.1%,
      95% CI 57.3-82.6) of A1C 6.5%, compared to the younger age groups. CONCLUSION:
      OGTT is preferable for diagnosis of DM in older Southeast Asian adults.

PMID- 22465400
TI  - Stratifying healthcare costs using the Diabetes Complication Severity Index.
AB  - OBJECTIVE: We aim to determine whether healthcare costs for patients diagnosed
      with Type 2 Diabetes Mellitus (T2DM) are associated with the severity of diabetes
      complications as measured by the Diabetes Complication Severity Index (DCSI).
      METHODS: Retrospective cohort analysis was performed on a 2007 primary care
      cohort of T2DM patients. The DCSI is a 13-point scale, which comprises 7
      categories of complications and their severity levels. Healthcare cost data from
      2008 and 2009 were used as primary outcome. Inpatient and outpatient costs
      incurred for services consumed by patients within the provider network were
      included. Generalized linear model with log-link and gamma distribution was used
      to predict healthcare costs. RESULTS: Of the 59,767 T2DM patients, 2977 (5.0%)
      deaths occurred and 1336 (2.2%) were lost to follow up. Healthcare cost was
      strongly associated with increase in DCSI score. Compared to patients without
      complications, those with more complications (higher DCSI score) had an increased
      risk of higher healthcare costs. Risk ratio (RR) increased from 1.25 (95%CI: 1.19
      1.32) for DCSI=1 to 1.61 (1.51-1.72) for DCSI=2; 2.10 (1.91-2.31) for DCSI=3;
      2.52 (2.21-2.87) for DCSI=4 and 3.62 (3.09-4.25) for DCSI>=5. As a continuous
      score, a one-point increase in the DCSI was associated with a cost increase of
      27% (95%CI: 1.25-1.29). CONCLUSION: The DCSI score is a useful tool for
      predicting direct healthcare costs. The DCSI can be used to triage high-risk
      patients for more focused secondary prevention interventions at primary care
      level, in a bid to lower overall healthcare costs.

PMID- 22465401
TI  - The Melithaeidae (Cnidaria: Octocorallia) of the Ryukyu Archipelago: molecular
      and morphological examinations.
AB  - The family Melithaeidae (Octocorallia: Alcyonacea) is distributed in the West
      Pacific, Indian Ocean and the Red Sea. They are most abundant in warmer waters
      but can also be found in temperate waters. At present six genera are assigned to
      this family (Melithaea, Mopsella, Clathraria, Acabaria, Wrightella and
      Asperaxis), however overlapping characteristics make this group's taxonomic
      identification difficult and their relationships unclear. There are only a few
      reports from the Ryukyu Archipelago in southern Japan of melithaeids and most
      other octocorals, despite the islands being an area of high octocoral diversity.
      To help resolve the taxonomic confusion in this family, samples from various
      Ryukyu Archipelago locations were collected and DNA sequences of nuclear 28S
      ribosomal DNA and mitochondrial cytochrome oxidase I (COI) were obtained.
      Additionally, SEM micrographs of the sclerites of specimens were taken to further
      confirm the molecular results. Three strongly supported clades were recovered
      from the COI and 28S rDNA analyses, corresponding to Melithaea, Acabaria, and
      Mopsella, and in most cases clades were clearly related with the sclerite shape
      reported for each genus. These results show clearly that molecular differences
      are present between the three genera, and also demonstrates the strong need of
      other molecular markers for resolving intra-generic phylogenies. Our results
      provide baseline data for future studies of this octocoral family, not only on
      taxonomy, but also with regards to their distribution in the Ryukyu Islands.

PMID- 22465402
TI  - Phylogenetic analysis of ticks (Acari: Ixodida) using mitochondrial genomes and
      nuclear rRNA genes indicates that the genus Amblyomma is polyphyletic.
AB  - Our understanding of the phylogenetic relationships among tick lineages has been
      limited by the lack of resolution provided by the most commonly used phylogenetic
      markers. Mitochondrial genomes are increasingly used to address controversial
      phylogenetic relationships. To date, the complete mitochondrial genomes of eleven
      tick species have been sequenced; however, only three of these species are
      metastriate ticks, the most speciose lineage of ticks. In this study, we present
      the nucleotide sequences of the complete mitochondrial genomes of five more
      species of metastriate ticks: Amblyomma elaphense, Amblyomma fimbriatum,
      Amblyomma sphenodonti, Bothriocroton concolor and Bothriocroton undatum. We use
      complete mitochondrial genome sequences to address the phylogenetic placement of
      two morphologically 'primitive' species -Am. elaphense and Am. sphenodonti - with
      respect to the genus Amblyomma. Our analysis of these five mitochondrial genomes
      with the other eleven tick mitochondrial genomes, as well as analysis of nuclear
      rRNA genes, provides strong evidence that the genus Amblyomma is polyphyletic
      with the inclusion of Am. sphenodonti and Am. elaphense. A new genus or two new
      genera may be required to describe Am. sphenodonti and Am. elaphense. It is also
      possible that these two species are sisters to two established genera,
      Bothriocroton in the case of Am. sphenodonti, and Haemaphysalis in the case of
      Am. elaphense. However, other arrangements of these taxa cannot be excluded with
      the current data. Thus, while Am. sphenodonti and Am. elaphense do not belong in
      the genus Amblyomma, the phylogenetic placement of these two species cannot be
      resolved without more data from metastriate ticks, either greater sampling of
      mitochondrial genomes, or a large data set of nuclear genes.

PMID- 22465403
TI  - Quantifying nonuse in chronic stroke patients: a study into paretic, nonparetic,
      and bimanual upper-limb use in daily life.
AB  - OBJECTIVE: To quantify uni- and bimanual upper-limb use in patients with chronic
      stroke in daily life compared with healthy controls. DESIGN: Cross-sectional
      observational study. SETTING: Outpatient rehabilitation center. PARTICIPANTS:
      Patients with chronic stroke (n=38) and healthy controls (n=18). INTERVENTION:
      Not applicable. MAIN OUTCOME MEASURES: Upper-limb use in daily life was measured
      with an accelerometry-based upper-limb activity monitor, an accelerometer based
      measurement device. Unimanual use of the paretic and the nonparetic side and
      bimanual upper-limb use were measured for a period of 24 hours. Outcomes were
      expressed in terms of both duration and intensity. RESULTS: Patients used their
      unaffected limb much more than their affected limb (5.3h vs 2.4h), while controls
      used both limbs a more equal amount of time (5.4h vs 5.1h). Patients used their
      paretic side less than controls used their nondominant side and their nonparetic
      side more than controls their dominant side. The intensity with which patients
      used their paretic side was lower than that with which controls used their
      nondominant side, while that of the nonparetic side was higher than that of the
      dominant side of controls. Finally, patients used their paretic side almost
      exclusively in bimanual activities. During bimanual activities, the intensity
      with which they used their affected side was much lower than that of the
      nonaffected side. CONCLUSION: Our data show considerable nonuse of the paretic
      side, both in duration and in intensity, and both during unimanual and bimanual
      activities in patients with chronic stroke. Patients do compensate for this with
      increased use of the nonparetic side.

PMID- 22465404
TI  - Impact of tai chi on impairment, functional limitation, and disability among
      preclinically disabled older people: a randomized controlled trial.
AB  - OBJECTIVES: To test the effect of tai chi on the progression of preclinical
      disability to manifest disability compared with seated flexibility exercise, and
      to examine whether tai chi mediates delayed disability by reducing impairments in
      musculoskeletal, cardiovascular, and neurologic systems, and related functional
      limitations. DESIGN: Multisite parallel group individually randomized controlled
      trial. SETTING: General community. PARTICIPANTS: Preclinically disabled community
      dwelling people older than 70 years (n=503), without major medical conditions or
      moderate to severe cognitive impairment. INTERVENTION: Modified Sun style tai chi
      exercise compared with seated flexibility exercise, both programs delivered in
      groups for 60 minutes twice weekly for 24 weeks. MAIN OUTCOME MEASURES:
      Disability measured with the Late-Life Function and Disability Instrument.
      Secondary outcomes were impairments and functional limitations of the
      musculoskeletal, neurologic, and cardiovascular systems. RESULTS: There was
      little change within or between the 2 groups. The mean change in the Disability
      Frequency Score was 0.3 and 0.1 points (100-point scale) for the intervention and
      control groups, respectively (adjusted difference -.21; 95% confidence interval
      [CI] -.99 to .56). The mean change in the Disability Limitation Score was -0.1
      and -.04 points for the intervention and control groups, respectively (adjusted
      difference -0.6; 95% CI -2.31 to 1.11). There was little effect on impairments or
      functional limitations. A higher proportion of intervention participants ceased
      attending the exercise program (difference=17.9%, 95% CI 9.6-25.8). Multiple
      imputation of missing data did not change the results. CONCLUSIONS: Modified Sun
      style tai chi did not have an impact on impairment, functional limitations, or
      disability in preclinically disabled older people when delivered for 24 weeks.
      Withdrawal from the exercise classes was high but did not explain the null
      result. Improved compliance, or a longer or more intensive program, may be
      required.

PMID- 22465405
TI  - The development and validation of the vestibular activities and participation
      measure.
AB  - OBJECTIVES: To develop and validate a new self-report outcome measure named the
      Vestibular Activities and Participation (VAP) for people with vestibular
      disorders to examine their activities and participation according to the
      International Classification of Functioning Disability and Health. DESIGN: Delphi
      iterative survey for the development of the VAP and validation study. SETTING:
      Tertiary balance clinic. PARTICIPANTS: A panel of worldwide experts (n=17) in
      vestibular dysfunction participated in the development of the VAP, and patients
      (N=58) with vestibular disorders were enrolled in the validation of the VAP.
      INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: For the development of the
      VAP, an Internet-based survey of 55 activities and participation items was
      presented to the panel of experts and the percentage agreement per item was
      calculated. For the validation of the VAP, the VAP was completed twice to examine
      the test-retest reliability, the World Health Organization Disability Assessment
      Schedule II (WHODAS II) was used to examine the concurrent validity with the VAP,
      and the Dizziness Handicap Inventory (DHI) was used to examine the convergent
      validity of the VAP. RESULTS: After 2 rounds of the Delphi technique, the VAP was
      developed. The VAP total score had excellent test-retest reliability (intraclass
      correlation coefficient=.95; confidence interval=.91-.97) and good to excellent
      agreement per item indicated by the unweighted kappa (.41-.80) and the weighted
      kappa (.58-.94). The minimum detectable change at 95% confidence level of the VAP
      score was .58. The VAP had strong correlation (rho=.70; P<.05) with the WHODAS II
      and moderate to strong correlations (rho=.54-.74) with the DHI subscale and total
      scores. After adjustment for age, we found sex and self-reported imbalance to be
      independent explanatory variables of the transformed VAP total score.
      CONCLUSIONS: The VAP measure was developed to examine the disabling effect of
      vestibular disorders on people's activities and participation based on a
      standardized framework (the International Classification of Functioning
      Disability and Health). The VAP demonstrated excellent reliability and was
      validated with external instruments in people with vestibular disorders.

PMID- 22465406
TI  - alphaA-crystallin in the pathogenesis and intervention of experimental murine
      corneal neovascularization.
AB  - This study was to determine the potential roles of lens crystallins in the
      pathogenesis of corneal neovascularization (CorNV) and implications in therapy of
      CorNV-related diseases. Suture- or chemical burn-induced CorNV in different
      strains of mice were used. Changes of gene expression patterns were analyzed by
      microarray, and the results of interesting genes were confirmed by real-time
      quantitative PCR and Western blot. Mice deficient in alphaA-crystallin gene were
      used to evaluate the role of alphaA-crystallin in the development of CorNV. In
      some animals, exogenous alphaA-crystallin proteins were injected around time of
      CorNV induction. CorNV was assessed by slit-lamp, flat-mounts and histology. In
      BALB/C mice, the expression of alpha-, beta-, and gamma-crystallins were up
      regulated at day 5 and returned to baseline level at day 10 of suture-induced
      CorNV, but remained up-regulated from day 6 to day 14 of chemical burn-induced
      CorNV. In chemical burn-induced CorNV in C57BL/6J mice, however, they were down
      regulated at day 6. Corneal crystallins were down-regulated in both CorNV models
      at all time points in both BALB/c and C57BL/6J mice. Comparison of CorNV
      development in alphaA-crystallin-deficient mice and that in wild-type mice
      revealed no significant difference. Subconjunctival injection of alphaA
      crystallin significantly attenuated suture-induced CorNV, and the inhibitory
      activity might be implemented by the increased expression of soluble VEGFR-1. In
      conclusion, the expression patterns of lens crystallins were time- and strain
      dependent but different from that of corneal crystallins in mouse CorNV models.
      Exogenous alphaA-crystallin protein attenuated CorNV, potentially by increasing
      the expression of soluble VEGFR-1.

PMID- 22465407
TI  - Activation of neural progenitor cells in human eyes with proliferative
      vitreoretinopathy.
AB  - In addition to the ability for self-renewal and functional differentiation,
      neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted
      migration. In lower vertebrates, retinal injury is known to activate NSCs in the
      ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in
      the ciliary body epithelium (CE) and in Muller glia in the peripheral retina (PR)
      of the adult human eye. However, these cells seem to be quiescent in the adult
      human eye and recent reports have shown that CE cells have limited properties of
      NSCs. In order to further clarify whether NSCs exist in the adult human eye, we
      tested whether NSC-like cells could be activated in eyes with proliferative
      vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in
      human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse
      model of PVR. Furthermore, cells isolated from vitreous samples obtained during
      vitrectomies for retinal detachment were directly fixed or cultured in a stem
      cell-promoting medium and compared to cells cultured from the post-mortem retina
      and CE. In situ characterization of the normal eyes revealed robust expression of
      markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the
      proximal pars plana region and the PR, the latter population also staining for
      the glial marker GFAP. Although there were higher numbers of dividing cells in
      the CE of PVR eyes than in controls, we did not detect NSC-associated markers in
      the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin
      activation was also found in the CE. In human PVR eyes, proliferation of both non
      glial and glial cells co-staining NSC-associated markers was evident around the
      ora serrata region. Spheres formed in 7/10 vitreous samples from patients with
      PVR compared to 2/15 samples from patients with no known PVR, and expressed glial
      - and NSC-associated markers both after direct fixation and repetitive passages.
      In conclusion, the adult human eye may harbor two different populations of
      neuroepithelial stem/progenitor cells; a non-glial population located in the
      proximal pars plana around peripheral cysts in addition to a population with
      Muller glia characteristics. Yet, we only found that the glial population was
      able to respond to retinal injury by targeted migration into the vitreous.

PMID- 22465409
TI  - MAP17 and the double-edged sword of ROS.
AB  - Reactive oxygen species, ROS, are beneficially involved in many signaling
      pathways that control development and maintain cellular homeostasis. In
      physiological conditions, a tightly regulated redox balance protects cells from
      injurious ROS activity, but if the balance is altered, it promotes various
      pathological conditions including cancer. Understanding the duality of ROS as
      cytotoxic molecules and key mediators in signaling cascades may provide novel
      opportunities for improved cancer therapy. MAP17 is a small 17-kDa non
      glycosylated membrane protein that is overexpressed in many tumors of different
      origins, including carcinomas. Immunohistochemical analysis of MAP17 during
      cancer progression demonstrates that overexpression of the protein strongly
      correlates with the progression of most types of tumor. Tumor cells that
      overexpress MAP17 show an increased tumoral phenotype associated with an increase
      in ROS. However, in non-tumor cells MAP17 increases ROS, resulting in senescence
      or apoptosis. Therefore, in tumor cells, MAP17 could be a marker for increased
      oxidative stress and could define new therapeutic approaches. Here, we review the
      role of MAP17 as a putative oncogene, as well as its role in cancer and
      anticancer therapies.

PMID- 22465408
TI  - Stromal fibroblast-bone marrow-derived cell interactions: implications for
      myofibroblast development in the cornea.
AB  - The purpose of this study was to test the hypothesis that mouse corneal stromal
      fibroblast and bone marrow-derived cell interactions augment corneal
      myofibroblast generation and, if so, to study whether such interactions are
      mediated by paracrine or juxtacrine mechanisms. Mouse bone marrow-derived cells
      and mouse corneal stromal fibroblasts were obtained from both mice with green
      fluorescent protein (GFP) expressed in all cells and normal GFP- BL6 control
      mice. To study the interactions of the different cell types, GFP+ cells of one
      type were co-cultured with GFP- cells of the other type in Primaria plates (to
      monitor juxtacrine signaling) or Transwell System plates (to monitor paracrine
      effects mediated by soluble mediators). Both cell types were cultured at a cell
      density of 1 * 10(5) cells per ml. The percentage of alpha smooth muscle actin+
      myofibroblasts was significantly higher (ANOVA, p<0.001) when bone marrow-derived
      cells and mouse corneal stromal fibroblasts were co-cultured compared to when
      bone marrow-derived cells and mouse corneal stromal fibroblasts were cultured
      alone (control). The in vitro studies using GFP+ corneal fibroblasts or GFP+ bone
      marrow-derived cells demonstrated conclusively that both cells types could
      transform into myofibroblasts. However, the percentage of alpha smooth muscle
      actinassds+ myofibroblasts generated from either cell type precursor was higher
      when both cells were co-cultured together (juxtacrine) as compared to when bone
      marrow-derived cells and mouse corneal stromal fibroblasts were co-culture in
      different compartments of Transwell System (paracrine). Thus, more alpha smooth
      muscle actin+ GFP+ myofibroblasts were generated from GFP+ corneal stromal
      fibroblasts when GFP- bone marrow-derived cells were present and more alpha
      smooth muscle actin+ GFP+ myofibroblasts were generated from GFP+ bone marrow
      derived cells when GFP- corneal stromal fibroblasts were present. Polyclonal anti
      human latency associated peptide (LAP) (transforming growth factor-beta1)
      neutralizing antibody (a-LAP) and/or transforming growth factor-beta type I
      receptor kinase inhibitor (LY-364947) inhibited the generation of alpha smooth
      muscle actin+ myofibroblasts from either precursor cell in Transwell System co
      culture experiments. These data suggest that TGFbeta is a paracrine modulator
      that regulates the generation of myofibroblasts from either corneal fibroblasts
      or bone marrow-derived cell precursors.

PMID- 22465410
TI  - The "bone within a bone" sign in idiopathic hypoparathyroidism.

PMID- 22465411
TI  - Using genetic algorithm in reconstructing single individual haplotype with
      minimum error correction.
AB  - Discovering ways to reconstruct reliable Single Individual Haplotypes (SIHs)
      becomes one of the core issues in the whole-genome research nowadays as previous
      research showed that haplotypes contain more information than individual Singular
      Nucleotide Polymorphisms (SNPs). Although with advances in high-throughput
      sequencing technologies obtaining sequence information is becoming easier in
      today's laboratories, obtained sequences from current technologies always contain
      inevitable sequence errors and missing information. The SIH reconstruction
      problem can be formulated as bi-partitioning the input SNP fragment matrix into
      paternal and maternal sections to achieve minimum error correction (MEC) time;
      the problem that is proved to be NP-hard. Several heuristics or greedy algorithms
      have already been designed and implemented to solve this problem, most of them
      however (1) do not have the ability to handle data sets with high error rates
      and/or (2) can only handle binary input matrices. In this study, we introduce a
      Genetic Algorithm (GA) based method, named GAHap, to reconstruct SIHs with lowest
      MEC times. GAHap is equipped with a well-designed fitness function to obtain
      better reconstruction rates. GAHap is also compared with existing methods to show
      its ability in generating highly reliable solutions.

PMID- 22465412
TI  - Taste masked lipid pellets with enhanced release of hydrophobic active
      ingredient.
AB  - Solid lipid extrusion is a suitable technique to produce oral dosage forms with
      improved taste properties. The design of a lipid formulation for poorly water
      soluble drugs is a challenge because of the poor dissolution and potential
      bioavailability problems. In this study, solid lipid extrusion at room
      temperature was applied for the formulation development of the BCS Class II drug
      NXP 1210. Powdered hard fat (Witocan((r)) 42/44 mikrofein), glycerol distearate
      (Precirol((r)) ato 5) and glycerol trimyristate (Dynasan((r)) 114) were
      investigated as lipid binders. Different amounts of polyvinylalcohol (PVA)
      polyethyleneglycol (PEG)-graft copolymer (Kollicoat((r)) IR) and crospovidone
      (Polyplasdone((r)) Xl-10) were scrutinized as solubilizers. The dissolution
      profiles depicted a short lag time (about 2min) and then fast and complete
      dissolution of NXP 1210 by increasing the amount of crospovidone. The initial
      release was more delayed with an increased amount of PVA-PEG-graft copolymer.
      Dissolution rate could also be influenced by changing the lipid binder from pure
      hard fat into a mixture of hard fat, glycerol distearate and glycerol
      trimyristate. The formulations are feasible for taste-masked granules or pellets
      containing poorly soluble drugs.

PMID- 22465413
TI  - Mesoporous silica nanoparticles for the improved anticancer efficacy of cis
      platin.
AB  - We designed a novel cis-platin (CP) delivery system by modification of mesoporous
      silica nanoparticle (MSN) surfaces with a carboxylate group through a hydrazone
      bond. The further immobilization of CP can be achieved through the coordination
      of the carboxylate-modified MSN surfaces with the hydroxo-substituted CP. This
      new formulation can efficiently increase efficiency of both the cellular uptake
      and the drug release under endosomal or lysosomal pHs; therefore, the anti
      proliferative effect of this new formulation on the colon cancer cell line (HT
      29) was twenty times more than the free CP molecules. In addition, the
      encapsulation of CP complexes in the confined spaces of MSNs can decrease non
      specific release from enzymatic hydrolysis because most hydrolytic enzymes have
      diameters considerably greater than the pore size of MSNs. The DNA fragmentation
      and caspase-3 activity assay showed that the apoptosis was induced by DNA damages
      and then an increase in caspase-3 activity. Thus, the TA-MSN-carboxylate-CP
      samples were induced cell apoptosis through the caspase-3 dependent pathway.
      Moreover, the hemolysis assay also indicated that the exposure of the carboxylate
      modified MSNs in red blood cells (RBCs) did not observe the release of red
      hemoglobin from the cell lysis, and the further exposure of the TA-MSN
      carboxylate-CP complexes to RBCs also did not observe notably the lysis of RBCs
      under the effectively therapeutic dosage. Therefore, our design of MSN with
      controllable release of CP has highly therapeutic effects and is highly
      biocompatible; however, a low cytotoxicity and site effect were observed.

PMID- 22465414
TI  - Modulation of microglial activation enhances neuroprotection and functional
      recovery derived from bone marrow mononuclear cell transplantation after cortical
      ischemia.
AB  - Activated microglia may exacerbate damage in neural disorders; however, it is
      unknown how they affect stem cells transplanted after stroke. Focal ischemia was
      induced by microinjections of 40 pmol of endothelin-1 into the motor cortex of
      adult rats. Ischemic animals were treated with sterile saline (n = 5), bone
      marrow mononuclear cells (BMMCs, n = 8), minocycline (n = 5) or concomitantly
      with minocycline and BMMCs (n = 5). BMMC-treated animals received 5 * 10(6)BMMCs
      through the caudal vein 24h post-ischemia. Behavioral tests were performed to
      evaluate functional recovery. Morphometric and histological analyses were
      performed to assess infarct area, neuronal loss and microglia/macrophage
      activation up to 21 days post-ischemia. Treatments with minocycline, BMMCs or
      minocycline-BMMCs reduced infarct area, increased neuronal survival and decreased
      the number of caspase-3+ and ED-1+ cells, but these effects were more prominent
      in the minocycline-BMMC group. Behavioral analyses using the modified sticky-tape
      and open-field tests showed that ischemic rats concomitantly treated with BMMCs
      and minocycline showed better motor performance than rats treated with BMMCs or
      minocycline only. The results suggest that proper modulation of the inflammatory
      response through the blockage of microglia activation enhances neuroprotection
      and functional recovery induced by intravenous transplantation of BMMCs after
      motor cortex ischemia.

PMID- 22465415
TI  - Autophagy induced by resveratrol prevents human prion protein-mediated
      neurotoxicity.
AB  - Our previous study revealed that resveratrol blocks prion protein peptide PrP(106
      126)-induced neurotoxicity. However, the mechanism of resveratrol-mediated
      neuroprotection in prion diseases is not clear. Resveratrol initiates
      neuroprotective effects via the activation of autophagy, which protects
      organelles, cells, and organisms against misfolded protein-disorders, including
      Alzheimer's disease and Parkinson's disease via regulation of mitochondrial
      homeostasis. Thus, we focused on elucidating the mechanisms responsible for
      resveratrol-mediated neuroprotection related to mitochondrial homeostasis as a
      result of autophagy activation. Resveratrol prevented PrP(106-126)-induced
      neuronal cell death by activating autophagy. Moreover, resveratrol-induced
      autophagy prevented the PrP(106-126)-induced reduction in mitochondrial potential
      and translocation of Bax to the mitochondria and cytochrome c release. Our
      results indicate that treatment with resveratrol appears to protect against
      neurotoxicity caused by prion protein peptides and the neuroprotection is induced
      by resveratrol-mediated autophagy signals.

PMID- 22465416
TI  - Everything you always wanted to know about nerve, but were afraid to ask.

PMID- 22465417
TI  - Type III Takayasu's arteritis in a pediatric patient. Case report and review of
      the literature.
AB  - Takayasu's arteritis (TA), also known as "pulseless disease", is the third most
      common vasculitis in childhood. It is a chronic, idiopathic, granulomatous
      vasculitis that involves large vessels. It occurs most commonly in females with a
      4:1 ratio over males; the average age of appearance is 26 years. Its cause is
      unknown. Here we report the case of a 7-year-old girl, with type III TA according
      to the Numano classification, in the ischemic phase, treated with corticosteroids
      and immunosuppressive agents and early angioplasty due to the severity of the
      disease. The outcome was satisfactory. The diagnosis of TA in children under 10
      years of age is made only in 2% of them. The delay in diagnosis reaches a mean of
      19 months. The course of the disease is variable despite surgical and
      immunosuppressive treatment.

PMID- 22465418
TI  - Characteristics of patients with spondyloarthritis followed in rheumatology units
      in Spain. emAR II study.
AB  - OBJECTIVE: To describe the main demographic and clinical features of patients
      with spondyloarthropaties in Spain. PATIENTS AND METHODS: Review of randomized
      clinical charts of patients with spondyloarthropaties with at least one visit to
      the rheumatologist in the previous two years. Information was collected on
      demographic and clinical data (duration of illness, diagnostic category, disease
      activity, extrarticular manifestations, comorbidity and work disability).
      RESULTS: 1,168 patients were included in the study. Their median age was 49.2
      years (39.7-60.5), 68.0% were males, and median time of disease was 105.1 month
      (48.4-192.5). The diagnoses and clinical data such as the BASDAI were reported
      only in 34,0% of the patients. The most widely used measure of metrology, the
      Schober test, was missing in 37.7% of the clinical charts. The patients included
      had the following diagnoses: Ankylosing spondylitis (n = 629, 55.2%), Psoriatic
      arthritis (n= 253, 22.2%), Undifferentiated spondyloarthritis (n = 184, 16.1%),
      Arthritis associated to Inflammatory bowel disease (n= 50, 4.4%), and Reactive
      arthritis (n= 16, 1.4%). The most common extraarticular manifestations were
      psoriasis (20.8%), anterior uveitis (19.4%), and enthesitis (16.9%). Some kind of
      work disability was reported in 8.3% of the patients. CONCLUSIONS: Demographic
      and clinical characteristics of patients with spondyloarthropaties in Spain do
      not differ as a whole from other published studies, except for Undifferentiated
      Spondyloarthritis, which was more likely in our patients than in other studies.
      The quality of the records of activity in the clinical charts could be improved.

PMID- 22465419
TI  - Imprinted gene expression in fetal growth and development.
AB  - Experimental studies showed that genomic imprinting is fundamental in
      fetoplacental development by timely regulating the expression of the imprinted
      genes to overlook a set of events determining placenta implantation, growth and
      embryogenesis. We examined the expression profile of 22 imprinted genes which
      have been linked to pregnancy abnormalities that may ultimately influence
      childhood development. The study was conducted in a subset of 106 placenta
      samples, overrepresented with small and large for gestational age cases, from the
      Rhode Island Child Health Study. We investigated associations between imprinted
      gene expression and three fetal development parameters: newborn head
      circumference, birth weight, and size for gestational age. Results from our
      investigation show that the maternally imprinted/paternally expressed gene ZNF331
      inversely associates with each parameter to drive smaller fetal size, while
      paternally imprinted/maternally expressed gene SLC22A18 directly associates with
      the newborn head circumference promoting growth. Multidimensional Scaling
      analysis revealed two clusters within the 22 imprinted genes which are
      independently associated with fetoplacental development. Our data suggest that
      cluster 1 genes work by assuring cell growth and tissue development, while
      cluster 2 genes act by coordinating these processes. Results from this
      epidemiologic study offer solid support for the key role of imprinting in
      fetoplacental development.

PMID- 22465420
TI  - Modulation of the biochemical composition of amniotic and allantoic fluids as a
      control mechanism of feline foetal development.
AB  - Amniotic fluid exerts a protective function and is an essential component for
      foetal development and maturation during pregnancy. However, little is known
      about the exact physiological functions of foetal fluids in this process as well
      as their biochemical composition in cats. In the present study, the biochemical
      composition of amniotic and allantoic fluids and maternal serum in pregnant
      queens was compared after performing an ovariohysterectomy. Fifteen queens were
      included in the study and distributed in four different groups, D(30), D(40),
      D(50) and D(60), according to their gestational age. Foetal fluids showed
      thoroughly greater concentrations of dissociate and total bilirubin, bile acids
      and gamma-glutamyl transferase than those of maternal serum, whereas albumin,
      total protein, alanine-transferase, creatine-kinase, amylase, lipase,
      triglycerides, cholesterol, HDL-cholesterol, and LDL-cholesterol were
      significantly lower, as compared to maternal serum. Other parameters like
      alkaline phosphatase, uric acid, creatinine, and electrolytes showed significant
      differences at specific stages of pregnancy, when compared to maternal serum.
      Lactate and cortisol significantly increased at the end of the pregnancy in
      foetal fluids, when compared with maternal serum. No significant differences
      between foetal fluids and maternal serum were observed for aspartate
      aminotransferase, lactate dehydrogenase, urea, phosphorus and glucose. According
      to our results, foetal fluids composition is not a result of simple filtration
      from maternal blood, the fetus being an active element involved in the production
      of the same and reflecting organ development and maturation.

PMID- 22465421
TI  - Identification of anti-retinal antibodies in patients with age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in industrial counties. Recent findings indicate that the autoimmunity
      is involved in the pathogenesis of the disease. However, there is no autoantibody
      biomarker applied in a clinical setting for diagnosis and prognosis of AMD. In
      order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse
      retinal tissue proteins were separated by 2-dimensional electrophoresis and the
      proteins in the immunoblots that were specific for dry and wet AMD patients IgG
      were identified by LC-MS/MS. Retinol-binding protein 3 and aldolase C (ALDOC)
      were mainly recognized by IgG form wet AMD patients. Pyruvate kinase M2 (PKM2)
      was targeted by both dry and wet AMD and level of anti-PKM2 IgG antibody was
      correlated best with the stage of AMD. Expression of ALDOC and PKM2 was decreased
      in mouse retina from aging whereas PKM2 deposit on RPE was increased in aged
      mice. Our data demonstrate that sera of AMD patients contain autoantibodies
      against retinal proteins and anti-PKM2 IgG serves as a biomarker for diagnosis
      and prognosis of AMD. Further investigation of the association of anti-retinal
      antibody level with expression level of antigens in retina will be needed to
      reveal the disease pathogenesis.

PMID- 22465423
TI  - A community empowerment strategy embedded in a routine dengue vector control
      programme: a cluster randomised controlled trial.
AB  - The non-sustainability of vertically organised dengue vector control programmes
      led to pleas for changing the emphasis towards community-based strategies. We
      conducted a cluster randomised controlled trial with 16 intervention and 16
      control clusters to test the effectiveness of a community empowerment strategy
      intertwined with the routine dengue vector control programme in La Lisa, Havana
      City, Cuba. The intervention included four components on top of routine control:
      organisation and management; entomological risk surveillance; capacity building;
      and community work for vector control. In the control clusters, routine
      activities continued without interference. The community participation score
      increased from 1.4 to 3.4. Good knowledge of breeding sites increased by 52.8%
      and 27.5% in the intervention and control clusters, respectively. There were no
      changes in adequate Aedes aegypti control practices at household level in the
      control clusters, but in the intervention clusters adequacy increased by 36.2%.
      At baseline, the Breteau indices (BI) were approximately 0.1 and were comparable;
      they fluctuated over time but became different with the launch of the community
      based dengue control activities in the intervention clusters. Over the
      intervention period, the BI remained 53% (95% CI 22-92%) lower in these clusters
      than in the control clusters. The empowerment strategy increased community
      involvement and added effectiveness to routine A. aegypti control.

PMID- 22465422
TI  - IL-21R expression on CD8+ T cells promotes CD8+ T cell activation in
      coxsackievirus B3 induced myocarditis.
AB  - IL-21 is a multi-functional cytokine which can promote survival, proliferation
      and activation of T and B lymphocytes including CD8 T cells. Previous studies
      have shown that autoimmune CD8+ T cells are the primary pathogenic effector cell
      in coxsackievirus B3 (CVB3) induced myocarditis in C57Bl/6 mice. To evaluate the
      role of IL-21 in promoting CD8+ T cell mediated cardiac injury in myocarditis,
      C57Bl/6 and IL-21RKO mice were infected with CVB3. IL-21RKO mice developed
      significantly less myocarditis than C57Bl/6 animals although cardiac virus titers
      were equivalent between the mouse strains. Numbers of CD8+IFNgamma+ cells were
      decreased in IL-21RKO mice but numbers of either CD4+IFNgamma+ or CD4+IL-4+ cells
      were not significantly different from C57Bl/6 animals indicating a selective
      effect of IL-21 signaling on the CD8+ T cell response. To confirm that IL-21
      signaling exclusively functions at the level of the CD8+ T cell in CVB3 induced
      myocarditis, purified CD8+ cells were isolated from either C57Bl/6 or IL-21RKO
      donors and adoptively transferred into CD8KO recipients prior to CVB3 infection.
      CD8KO recipients given either C57Bl/6 or IL-21RKO CD8+ cells showed equivalent
      reconstitution of the CD8+ cells in the spleen but the recipients given C57Bl/6
      CD8+ cells showed significantly greater myocarditis than recipients of IL-21RKO
      CD8+ cells. These data demonstrate that IL-21 signaling directly in the CD8+ cell
      population is required for CVB3-induced myocarditis.

PMID- 22465424
TI  - Relative contribution of CTR1 and DMT1 in copper transport by the blood-CSF
      barrier: implication in manganese-induced neurotoxicity.
AB  - The homeostasis of copper (Cu) in the cerebrospinal fluid (CSF) is partially
      regulated by the Cu transporter-1 (CTR1) and divalent metal transporter-1 (DMT1)
      at the blood-CSF barrier (BCB) in the choroid plexus. Data from human and animal
      studies suggest an increased Cu concentration in blood, CSF, and brains following
      in vivo manganese (Mn) exposure. This study was designed to investigate the
      relative role of CTR1 and DMT1 in Cu transport under normal or Mn-exposed
      conditions using an immortalized choroidal Z310 cell line. Mn exposure in vitro
      resulted in an increased cellular 64Cu uptake and the up-regulation of both CTR1
      and DMT1. Knocking down CTR1 by siRNA counteracted the Mn-induced increase of
      64Cu uptake, while knocking down DMT1 siRNA resulted in an increased cellular
      64Cu uptake in Mn-exposed cells. To distinguish the roles of CTR1 and DMT1 in Cu
      transport, the Z310 cell-based tetracycline (Tet)-inducible CTR1 and DMT1
      expression cell lines were developed, namely iZCTR1 and iZDMT1 cells,
      respectively. In iZCTR1 cells, Tet induction led to a robust increase (25 fold)
      of 64Cu uptake with the time course corresponding to the increased CTR1.
      Induction of DMT1 by Tet in iZDMT1 cells, however, resulted in only a slight
      increase of 64Cu uptake in contrast to a substantial increase in DMT1 mRNA and
      protein expression. These data indicate that CTR1, but not DMT1, plays an
      essential role in transporting Cu by the BCB in the choroid plexus. Mn-induced
      cellular overload of Cu at the BCB is due, primarily, to Mn-induced over
      expression of CTR1.

PMID- 22465425
TI  - [The epidemiological approach of clefts lip and palate in the eastern of
      Democratic Republic of Congo].
AB  - OBJECTIVE: This study aims to present the epidemiological profile of clefts
      lip/palate observed in the eastern of Democratic Republic of Congo (DRC) from
      January 2002 to May 2004, period of civil wars. METHOD: It is a retrospective
      study realized at Doctors on Call for service Learning Center (DOCS LC) in
      Goma/DRC concerning 89 cases of cleft lip/palate operated during the same period.
      The data processing was facilitated by the software package SPSS 17.0 installed
      in the IT center of DOCS. RESULTS: The average age of the consultation is 9.9
      years with extreme of zero and 42 years. Both sexes are concerned: 50.6% of male
      and 49.4% of female. The more cleft extends from the superior lip to the palate
      through the alveolus, the more the frequency of the various types of clefts
      lips/palate decreases: 59.6% (simple clefts lip), 37.1% (labio-alveolar clefts),
      and 2.2% (cleft palate). The left incomplete cleft lip variety represents 33.7%
      of all varieties. Most of clefts lips/palate come from the first to the fifth
      pregnancy with a peak of frequency (19.1%) in the second pregnancy. No family
      history about congenital deformation was found from 97% of our patients.
      CONCLUSION: The epidemiology of cleft lip/palate in our area would be more
      connected to environmental factors than genetics: no family history of congenital
      deformation was seen for most of our patients during this period of civil war.

PMID- 22465426
TI  - PCSK9 inhibition: the next statin?

PMID- 22465427
TI  - Association between recurrent metastasis from stage II and III primary colorectal
      tumors and moderate microsatellite instability.
AB  - Colorectal cancer cells frequently have low levels of microsatellite instability
      (MSI-L) and elevated microsatellite alterations at selected tetranucleotide
      repeats (EMAST), but little is known about the clinicopathologic significance of
      these features. We observed that patients with stage II or III colorectal cancer
      with MSI-L and/or EMAST had shorter times of recurrence-free survival than
      patients with high levels of MSI (P = .0084) or with highly stable
      microsatellites P = .0415), based on Kaplan-Meier analysis. MSI-L and/or EMAST
      were independent predictors of recurrent distant metastasis from primary stage II
      or III colorectal tumors (Cox proportional hazard analysis: hazard ratio, 1.83;
      95% confidence interval, 1.06-3.15; P = .0301).

PMID- 22465428
TI  - Pan-histone deacetylase inhibitor panobinostat sensitizes gastric cancer cells to
      anthracyclines via induction of CITED2.
AB  - BACKGROUND & AIMS: Chemotherapy modestly prolongs survival of patients with
      advanced gastric cancer, but strategies are needed to increase its efficacy.
      Histone deacetylase (HDAC) inhibitors modify chromatin and can block cancer cell
      proliferation and promote apoptosis. METHODS: Gastric cancer cell lines were
      incubated with the HDAC inhibitor LBH589 (Panobinostat, Novartis, Germany);
      levels of proliferation, apoptosis, histone acetylation, and gene expression were
      determined. We identified factors downstream of HDAC that regulated
      chemoresistance. The effects of combination chemotherapy of HDAC inhibitors and
      anthracyclines were studied in CEA424/SV40 T-antigen (CEA/Tag) transgenic mice,
      which develop gastric tumors. We analyzed gastric tumor samples from patients
      using immunohistochemistry. RESULTS: HDAC2 was expressed in human gastric cancer
      cell lines and tumor samples, as well as in gastric tumors from CEA/Tag mice,
      compared with non-neoplastic gastric tissue. LBH589 inhibited proliferation of
      cancer cells in vitro. LBH589 down-regulated expression of genes that mediate
      anthracycline resistance by activating expression of Cbp/p300-interacting
      transactivator, with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), a gene that
      mediates sensitivity to chemotherapeutics. Pre-incubation of cells with an HDAC
      inhibitor and overexpression of CITED2-sensitized gastric cell lines to
      anthracycline-mediated cell death. In CEA/Tag mice, LBH589 induced tumor-cell
      expression of CITED2 and increased the efficacy of anthracycline to reduce tumor
      growth. Levels of CITED2 were increased in gastric tumor samples from patients
      who had complete responses to epirubicin. CONCLUSIONS: The HDAC inhibitor LBH589
      can overcome the resistance of mouse gastric cancer cells to anthracyclines by
      inducing expression of CITED2. Levels of CITED2 in gastric tumors correlate with
      patients' response to epirubicin. LBH589 might be used to increase the response
      of patients to anthracyclines.

PMID- 22465429
TI  - A plant-derived flavonoid inhibits entry of all HCV genotypes into human
      hepatocytes.
AB  - BACKGROUND & AIMS: Interferon-based therapies for hepatitis C virus (HCV)
      infection are limited by side effects and incomplete response rates, particularly
      among transplant recipients. We screened a library of plant-derived small
      molecules to identify HCV inhibitors with novel mechanisms. METHODS: We isolated
      phenolic compounds from Marrubium peregrinum L (Lamiaceae). Replication of HCV
      RNA, virus production, and cell entry were monitored using replicons and
      infectious HCV. Inhibition of HCV was measured in hepatoma cells and primary
      human hepatocytes using luciferase reporter gene assays, core enzyme-linked
      immunosorbent assays, or infectivity titration. We tested the bioavailability of
      the compound in mice. RESULTS: We identified a flavonoid, ladanein (BJ486K), with
      unreported antiviral activity and established its oral bioavailability in mice.
      Natural and synthetic BJ486K inhibited a post-attachment entry step, but not RNA
      replication or assembly; its inhibitory concentration 50% was 2.5 MUm. BJ486K was
      effective against all major HCV genotypes, including a variant that is resistant
      to an entry inhibitor; it prevented infection of primary human hepatocytes.
      Combined administration of BJ486K and cyclosporine A had a synergistic effect in
      inhibition of HCV infection. CONCLUSIONS: BJ486K has oral bioavailability and
      interferes with entry of HCV into cultured human hepatocytes. It synergizes with
      cyclosporine A to inhibit HCV infection. Its inhibitory effects are independent
      of HCV genotype, including a variant that is resistant to an entry inhibitor
      against scavenger receptor class B type I. Flavonoid derivatives therefore might
      be developed as components of combination therapies because they are potent,
      broadly active inhibitors of HCV entry that could prevent graft reinfection after
      liver transplantation.

PMID- 22465430
TI  - Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem
      cells in mice.
AB  - BACKGROUND & AIMS: Prostaglandin-endoperoxide synthase (Ptgs)2 is an enzyme
      involved in prostaglandin production during the response to mucosal damage. Its
      expression is regulated, in part, by messenger RNA (mRNA)-binding proteins that
      control the stability of Ptgs2 mRNA. We used a precise system of colonic injury
      and repair to identify Ptgs2 mRNA-binding proteins. METHODS: We used endoscopy
      guided mucosal excision to create focal injury sites in colons of mice. Wound
      beds from wild-type, Ptgs2(-/-), Ptgs2(+/-), and Myd88(-/-) mice were analyzed at
      2-day intervals after injury for aspects of repair and Ptgs2 expression. We used
      cultured colonic mesenchymal stem cells (cMSCs) that express Ptgs2 to identify
      and analyze molecules that regulate Ptgs2 expression. RESULTS: Ptgs2(-/-) mice
      had defects in wound repair, validating the biopsy technique as a system to study
      the regulation of Ptgs2. Ptgs2(+/-) mice had similar defects in wound healing, so
      full induction of Ptgs2 is required for wound repair. In wild-type mice, levels
      of Ptgs2 mRNA increased significantly in the wound bed 2 and 4 days after injury;
      the highest levels of Ptgs2 were observed in cMSCs. In a functional short hairpin
      RNA knockdown screen, we identified Igf2bp1, a VICKZ (Vg1 RNA binding protein,
      Insulin-like growth factor II mRNA binding protein 1, Coding region determinant
      binding protein, KH domain containing protein overexpressed in cancer, and
      Zipcode-binding protein-1) mRNA-binding protein, as a regulator of Ptgs2
      expression in cMSCs. Igf2bp1 also interacted physically with Ptgs2 mRNA. Igf2bp1
      expression was induced exclusively in wound-bed cMSCs, and full induction of
      Ptgs2 and Igf2bp1 during repair required Myd88. CONCLUSIONS: We identified
      Igf2bp1 as a regulator of Ptgs2 mRNA in mice. Igf2bp1 is required for full
      induction of Ptgs2 mRNA in cMSCs.

PMID- 22465431
TI  - An RNA aptamer that binds carcinoembryonic antigen inhibits hepatic metastasis of
      colon cancer cells in mice.
AB  - BACKGROUND & AIMS: Carcinoembryonic antigen (CEA) is expressed by many types of
      cancer cells; its overexpression induces cell adhesion, increases resistance to
      anoikis, and promotes hepatic metastasis of colon cancer cells. The amino acid
      sequence PELPK in its hinge region, between the N and A1 domains, is required for
      migration of cancer cells to the liver. We sought to identify ligands of this
      domain for use in diagnosis and therapy. METHODS: We screened for RNA aptamers
      against the domain of CEA required for metastasis using systematic evolution of
      ligands by exponential enrichment. The specificity and affinity of the aptamer
      for CEA protein were characterized by mobility shift, uptake, and surface plasmon
      resonance assays. We analyzed the effects of the aptamer on metastatic properties
      of cells, as well as metastasis of colon cancer cells in mice. RESULTS: Using
      systematic evolution of ligands by exponential enrichment, we identified an RNA
      aptamer that bound to the PELPK sequence in CEA with high affinity and
      specificity. The isolated aptamer bound specifically to CEA-positive cells and
      inhibited interactions between CEA and heterogeneous nuclear ribonucleoprotein
      M4. The aptamer inhibited homotypic aggregation, migration, and invasion by CEA
      positive cancer cells, but did not affect adhesion of endothelial cells. The
      aptamer induced colon cancer cell anoikis by interrupting the interaction between
      death receptor 5 and CEA. The aptamer prevented metastasis of human colon cancer
      cells to the livers of mice. CONCLUSIONS: An RNA aptamer that binds to the PELPK
      sequence in CEA inhibits its interactions with heterogeneous nuclear
      ribonucleoprotein M4 and death receptor 5, migration and invasion by colon cancer
      cells, and hepatic metastasis of colon cancer cells in mice. It promoted cancer
      cell anoikis and might be used to identify CEA-positive tumors in patients or be
      developed as an anti-cancer reagent.

PMID- 22465432
TI  - The quality of care provided to patients with cirrhosis and ascites in the
      Department of Veterans Affairs.
AB  - BACKGROUND & AIMS: Ascites are the most common complication of cirrhosis.
      Evidence-based guidelines define the criteria and standards of care for patients
      with cirrhosis and ascites. However, little is known about the extent to which
      patients with ascites meet these standards. METHODS: We evaluated the quality of
      ascites care, measured by 8 explicit Delphi panel-derived quality indicators, in
      774 patients with cirrhosis and ascites, seen at 3 Veterans Affairs Medical
      Centers between 2000 and 2007. We also conducted a structured implicit review of
      patients' medical charts to determine whether patient refusal, outside care, or
      other justifiable exceptions to care processes account for nonadherence to the
      quality indicators. RESULTS: Quality scores (maximum 100%) varied among
      individual indicators, ranging from 30% for secondary prophylaxis of spontaneous
      bacterial peritonitis, to 90% for assays for cell number and type in the
      paracentesis fluid. In general, care targeted at treatment was more likely to
      meet standards than preventive care. Only 33.2% (95% confidence interval [CI]:
      29.9%-32.9%) of patients received all recommended care. Patients with no
      comorbidity (Deyo index 0 vs >3; odds ratio = 2.21; 95% CI: 1.43-3.43), who saw a
      gastroenterologist (odds ratio = 1.33; 95% CI, 1.01-1.74), or were seen in a
      facility with academic affiliation (odds ratio = 1.73; 95% CI: 1.29-2.35)
      received higher-quality care. Justifiable exceptions to indicated care,
      documented in charts, were common for patients with paracentesis after diagnosis
      with ascites, patients that received antibiotics for gastrointestinal bleeding,
      and patients that required diuretics. However, most patients did not have an
      explanation documented for nonadherence to recommended care. CONCLUSIONS: Health
      care quality, measured by whether patients received recommended services, was
      suboptimal for patients with cirrhosis-related ascites. Care that included
      gastroenterologists was associated with high quality. However, for some of the
      quality indicators, too many denominator exceptions existed to allow for accurate
      automated measurement.

PMID- 22465433
TI  - Classical swine fever outbreak containment using antiviral supplementation: a
      potential alternative to emergency vaccination and stamping-out.
AB  - Classical swine fever (CSF) outbreaks may result in huge economic losses to
      countries with densely populated pig areas (DPLAs). The EU minimum control
      measures require depopulation of infected farms, movement restrictions, zoning
      and surveillance (EU Minimum strategy). Emergency vaccination is authorised for
      DPLAs although the EU Minimum strategy plus culling in a 1-km ring around
      infected premises is preferred. Nonetheless, vaccination in a 2-km ring has been
      found equally effective as 1-km ring culling using stochastic modelling.
      Alternatives control measures (e.g. antiviral agents, in particular small
      molecule inhibitors of the CSFV replication) are being explored. Hence, the
      present study was set up to simulate inter-herd CSFV spread when antiviral
      molecules are supplemented to pig feed in a 1-km ring around infected farms. The
      effectiveness of the antiviral strategy for containing CSF outbreaks was compared
      to six other control scenarios including the EU Minimum strategy, the EU
      preferred policy for DPLAs and the use of 2-km ring vaccination. The InterSpread
      Plus model was adapted to the 2006 Belgian pig population and outbreak
      simulations were performed with a fast spreading CSFV strain entering a DPLA in
      Belgium. Four out of the seven control strategies resulted in outbreaks that were
      controlled by the end of the simulation period (i.e. 365 days). The distributions
      of the number of infected herds and the duration of the predicted outbreaks for
      these four control strategies were not different. This is the first report
      investigating CSF outbreak containment using antiviral molecules. Although
      antiviral supplementation was not found to perform any better than some other
      conventional strategies, such as pre-emptive culling and emergency vaccination,
      it might be worthwhile considering it further as additional tool in a response to
      CSF outbreaks.

PMID- 22465434
TI  - The age of transfused blood predicts hematocrit response among critically ill
      surgical patients.
AB  - BACKGROUND: In vitro data suggest that erythrocytes undergo storage time
      dependent degradation, eventuating in hemolysis. We hypothesize that transfusion
      of old blood, as compared with newer blood, results in a smaller increment in
      hematocrit. METHODS: We performed an analysis of packed red blood cell
      transfusions administered in the surgical intensive care unit. Age of blood was
      analyzed as continuous, dichotomized at 14 days (old vs new), and grouped by
      weeks old. RESULTS: A total of 136 U of packed red blood cells were given to 52
      patients; 110 (80.9%) were 14 days old or more. A linear, inverse correlation was
      observed between the age of blood and the increment in hematocrit (r(2) = -.18, P
      = .04). The increment in hematocrit was greater after transfusion of new as
      compared with old blood (5.6% vs 3.5%, respectively; P = .005). A linear
      relationship also was observed between the age of transfused blood in weeks and
      the increment in hematocrit (P = .02). CONCLUSIONS: There is an inverse
      relationship between the age of blood and the increment in hematocrit. The age of
      blood should be considered before transfusion of surgical patients with intensive
      care unit anemia.

PMID- 22465435
TI  - Femoral vessel blood flow dynamics after totally extraperitoneal versus Stoppa
      procedure in bilateral inguinal hernias: the need for evidence-based surgery.

PMID- 22465437
TI  - Contralesional spatial bias in chronic hemianopia: the role of (ec)centric
      fixation, spatial cueing and visual search.
AB  - Patients with homonymous hemianopia often show a contralesional shift towards
      their blind field when bisecting horizontal lines ('hemianopic line bisection
      error', HLBE). The reasons for this spatial bias are not well understood and
      debated. Eccentric fixation and adaptive orienting of eye movements towards the
      blind field have been suggested as hypothetical explanations but were not tested
      experimentally yet. Moreover, the role of spatial attention and visual search in
      the blind field are unsettled issues. Here, we tested in 20 stroke patients with
      chronic homonymous hemianopia (10 left-sided, 10 right-sided) without visual
      neglect, 10 healthy control subjects and 10 neurological control patients without
      hemianopia whether the HLBE is related to (a) eccentric fixation and (b) is
      influenced by spatial-attentional cueing (left, right) and (c) related to the
      degree of oculomotor compensation in the blind field. Perimetric mapping of the
      blind spot in the ipsilesional eye was performed in 39/40 subjects. Both
      hemianopic patient groups showed the typical HLBE towards their blind field,
      while the two control samples showed only a small but significant leftward shift
      known as pseudoneglect. The horizontal and vertical position of the blind spot in
      the ipsilesional eye was within normal limits in 38 out of 40 subjects, and did
      not differ significantly between the four samples. Moreover, the HLBE was not
      significantly correlated to the horizontal or vertical position of the centre of
      the blind spot, thus excluding eccentric fixation as an explanation for this
      spatial error. Furthermore, spatial cueing by manipulating the starting position
      of the bisection cue (left, right) did not affect the HLBE, arguing against
      attentional cueing effects well known from the line bisection error in patients
      with spatial neglect. Finally, the size of the saccadic search field in the
      scotoma was not significantly correlated to the HLBE in hemianopia. We conclude
      that eccentric fixation, contralesional hyperattention or ipsilesional
      hypoattention, or good or poor oculomotor compensation of the field loss itself
      are not likely causes of the HLBE in chronic homonymous hemianopia. Implications
      of these findings and alternative explanations are discussed.

PMID- 22465436
TI  - Dorsal striatal dopamine depletion impairs both allocentric and egocentric
      navigation in rats.
AB  - Successful navigation requires interactions among multiple but overlapping neural
      pathways mediating distinct capabilities, including egocentric (self-oriented,
      route-based) and allocentric (spatial, map-based) learning. Route-based
      navigation has been shown to be impaired following acute exposure to the
      dopaminergic (DA) drugs (+)-methamphetamine and (+)-amphetamine, but not the
      serotoninergic (5-HT) drugs (+/-)-3,4-methylenedioxymethamphetamine or (+/-)
      fenfluramine. The dopaminergic-rich neostriatum is involved in both allocentric
      and egocentric navigation. This experiment tested whether dorsal striatal DA loss
      using bilateral 6-hydroxydopamine (6-OHDA) injections impaired one or both types
      of navigation. Two weeks following 6-OHDA injections, rats began testing in the
      Cincinnati water maze (CWM) followed by the Morris water maze (MWM) for route
      based and spatial navigation, respectively. 6-OHDA treatment significantly
      increased latency and errors in the CWM and path length, latency, and cumulative
      distance in the MWM with no difference on cued MWM trials. Neostriatal DA levels
      were reduced by 80% at 2 and 7 weeks post-treatment. In addition, 6-OHDA
      increased DA turnover and decreased norepinephrine (NE) levels. 6-OHDA injections
      did not alter monoamine levels in the prefrontal cortex. The data support that
      neostriatal DA modulates both types of navigation.

PMID- 22465438
TI  - Feature precedence in processing multifeature visual information in the human
      brain: an event-related potential study.
AB  - In this article, we aimed to study whether feature precedence existed in the
      cognitive processing of multifeature visual information in the human brain. In
      our experiment, we paid attention to two important visual features as follows:
      color and shape. In order to avoid the presence of semantic constraints between
      them and the resulting impact, pure color and simple geometric shape were chosen
      as the color feature and shape feature of visual stimulus, respectively. We
      adopted an "old/new" paradigm to study the cognitive processing of color feature,
      shape feature and the combination of color feature and shape feature,
      respectively. The experiment consisted of three tasks as follows: Color task,
      Shape task and Color-Shape task. The results showed that the feature-based
      pattern would be activated in the human brain in processing multifeature visual
      information without semantic association between features. Furthermore, shape
      feature was processed earlier than color feature, and the cognitive processing of
      color feature was more difficult than that of shape feature.

PMID- 22465440
TI  - Animal models of L-DOPA-induced dyskinesia: an update on the current options.
AB  - Major limitations to the pharmacotherapy of Parkinson's disease (PD) are the
      motor complications resulting from L-DOPA treatment. Abnormal involuntary
      movements (dyskinesia) affect a majority of the patients after a few years of L
      DOPA treatment and can become troublesome and debilitating. Once dyskinesia has
      debuted, an irreversible process seems to have occurred, and the movement
      disorder becomes almost impossible to eliminate with adjustments in peroral
      pharmacotherapy. There is a great need to find new pharmacological interventions
      for PD that will alleviate parkinsonian symptoms without inducing dyskinesia. The
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned non-human primate
      model is an excellent symptomatic model of PD and was the first model used to
      reproduce L-DOPA-induced dyskinesia experimentally. As it recapitulates the motor
      features of human dyskinesia, that is, chorea and dystonia, it is considered a
      reliable animal model to define novel therapies. Over the last decade, rodent
      models of L-DOPA-induced dyskinesia have been developed, having both face
      validity and predictive validity. These models have now become the first-line
      experimental tool for therapeutic screening purposes. The application of
      classical 6-hydroxydopamine (6-OHDA) lesion procedures to produce rodent models
      of dyskinesia has provided the field with more dynamic tools, since the
      versatility of toxin doses and injection coordinates allows for mimicking
      different stages of PD. This article will review models developed in non-human
      primate and rodents to reproduce motor complications induced by dopamine
      replacement therapy. The recent breakthroughs represented by mouse models and the
      relevance of rodents in relation to non-human primate models will be discussed.

PMID- 22465441
TI  - Radial glia in the cerebellum of adult teleost fish: implications for the
      guidance of migrating new neurons.
AB  - In contrast to mammals, in teleost fish radial glia persist beyond early
      development. This persistence parallels the enormous potential of teleosts to
      continuously generate a large number of new neurons in dozens of specific
      proliferation zones in the adult brain. In the present study, we characterized in
      the teleost fish Apteronotus leptorhynchus the immunological properties of radial
      glia in the corpus cerebelli-a cerebellar subdivision with particularly high
      proliferative activity-and examined their possible function in the guidance of
      migrating young neurons. Radial glia stained immunopositive for glial fibrillary
      acidic protein (GFAP) and vimentin, and in most cases the two intermediate
      filament proteins co-localized. GFAP immunolabeling combined with
      immunohistochemistry against the mitotic marker 5-bromo-2'-deoxyuridine (BrdU)
      revealed an abundance of elongated BrdU-labeled nuclei closely apposed to, or
      localized within, GFAP-immunoreactive radial glia. The association of BrdU
      labeled nuclei and GFAP-immunoreactive radial glial fibers was particularly
      pronounced 2 days after BrdU administration, when the migratory activity of the
      young cells is highest. When the new cells reach the granular layer, they start
      expressing the neuronal marker protein Hu C/D, but continue their close
      association with radial glial fibers. These results suggest the role of radial
      glia in the guidance of migrating adult-born neurons in the teleostean
      cerebellum. This function appears to be mediated both by somal translocation and
      by a glial-guided mode of locomotion.

PMID- 22465442
TI  - EmaxDB: Availability of a first draft genome sequence for the apicomplexan
      Eimeria maxima.
AB  - Apicomplexan parasites are serious pathogens of animals and man that cause
      diseases including coccidiosis, malaria and toxoplasmosis. The importance of
      these parasites has prompted the establishment of genomic resources in support of
      developing effective control strategies. For the Eimeria species resources have
      developed most rapidly for the reference Eimeria tenella Houghton strain
      (http://www.genedb.org/Homepage/Etenella). The value of these resources can be
      enhanced by comparison with related parasites. The well characterised
      immunogenicity and genetic diversity associated with Eimeria maxima promote its
      use in genetics-led studies on coccidiosis and recommended its selection for
      sequencing. Using a combination of sequencing technologies a first draft assembly
      and annotation has been produced for an E. maxima Houghton strain-derived clone
      (EmaxDB; http://www.genomemalaysia.gov.my/emaxdb/). The assembly of a draft
      genome sequence for E. maxima provides a resource for comparative studies with
      Eimeria and related parasites as demonstrated here through the identification of
      genes predicted to encode microneme proteins in E. maxima.

PMID- 22465443
TI  - What lies beneath: molecular phylogenetics and ancestral state reconstruction of
      the ancient subterranean Australian Parabathynellidae (Syncarida, Crustacea).
AB  - The crustacean family Parabathynellidae is an ancient and significant faunal
      component of subterranean ecosystems. Molecular data were generated in order to
      examine phylogenetic relationships amongst Australian genera and assess the
      species diversity of this group within Australia. We also used the resultant
      phylogenetic framework, in combination with an ancestral state reconstruction
      (ASR) analysis, to explore the evolution of two key morphological characters
      (number of segments of the first and second antennae), previously used to define
      genera, and assess the oligomerization principle (i.e. serial appendage reduction
      over time), which is commonly invoked in crustacean systematics. The ASR approach
      also allowed an assessment of whether there has been convergent evolution of
      appendage numbers during the evolution of Australian parabathynellids. Sequence
      data from the mtDNA COI and nDNA 18S rRNA genes were obtained from 32
      parabathynellid species (100% of described genera and ~25% of described species)
      from key groundwater regions across Australia. Phylogenetic analyses revealed
      that species of each known genus, defined by traditional morphological methods,
      were monophyletic, suggesting that the commonly used generic characters are
      robust for defining distinct evolutionary lineages. Additionally, ancestral state
      reconstruction analysis provided evidence for multiple cases of convergent
      evolution for the two morphological characters evaluated, suggesting that caution
      needs to be shown when using these characters for elucidating phylogenetic
      relationships, particularly when there are few morphological characters available
      for reconstructing relationships. The ancestral state analysis contradicted the
      conventional view of parabathynellid evolution, which assumes that more
      simplified taxa (i.e. those with fewer-segmented appendages and setae) are
      derived and more complex taxa are primitive.

PMID- 22465439
TI  - Animal models of eating disorders.
AB  - Feeding is a fundamental process for basic survival and is influenced by genetics
      and environmental stressors. Recent advances in our understanding of behavioral
      genetics have provided a profound insight on several components regulating eating
      patterns. However, our understanding of eating disorders, such as anorexia
      nervosa, bulimia nervosa, and binge eating, is still poor. The animal model is an
      essential tool in the investigation of eating behaviors and their pathological
      forms, yet development of an appropriate animal model for eating disorders still
      remains challenging due to our limited knowledge and some of the more ambiguous
      clinical diagnostic measures. Therefore, this review will serve to focus on the
      basic clinical features of eating disorders and the current advances in animal
      models of eating disorders.

PMID- 22465444
TI  - DNAzyme-based turn-on chemiluminescence assays in homogenous media.
AB  - In this work, novel biosensing systems were developed for DNAzyme-based assays in
      homogenous aqueous media. The two halves of a horseradish peroxidase mimicking
      DNAzyme were assembled onto different gold nanoparticle surfaces through
      hybridization with corresponding linking DNA sequences. In the analyses, the
      target molecules were recognized by the linking DNA. This recognition broke the
      hybridization and released the DNAzyme halves from the nanoparticle surface into
      the solution. Together, both the DNAzyme halves combined with a cofactor hemin
      and turned into a catalytic hemin/G-quadruplex structure, which amplified the
      luminol oxidation for a turn-on chemiluminescence signaling. Based on this
      nanoparticle-based DNAzyme-halves design, only low background noise showed up
      within the homogenous solution and no separation was required in the detection
      steps. Aptasensor and DNA sensor were developed and analyses of the target
      molecules adenosine and target DNA were achieved down to 0.7 MUM and 0.3 nM
      respectively with satisfactory selectivity.

PMID- 22465445
TI  - Optimizing potentiometric ionophore and electrode design for environmental on
      site control of antibiotic drugs: application to sulfamethoxazole.
AB  - Potentiometric sensors are typically unable to carry out on-site monitoring of
      environmental drug contaminants because of their high limits of detection (LODs).
      Designing a novel ligand material for the target analyte and managing the
      composition of the internal reference solution have been the strategies employed
      here to produce for the first time a potentiometric-based direct reading method
      for an environmental drug contaminant. This concept has been applied to
      sulfamethoxazole (SMX), one of the many antibiotics used in aquaculture practices
      that may occur in environmental waters. The novel ligand has been produced by
      imprinting SMX on the surface of graphitic carbon nanostructures (CN)<500 nm. The
      imprinted carbon nanostructures (ICN) were dispersed in plasticizer and entrapped
      in a PVC matrix that included (or not) a small amount of a lipophilic additive.
      The membrane composition was optimized on solid-contact electrodes, allowing near
      Nernstian responses down to 5.2 MUg/mL and detecting 1.6 MUg/mL. The membranes
      offered good selectivity against most of the ionic compounds in environmental
      water. The best membrane cocktail was applied on the smaller end of a 1000 MUL
      micropipette tip made of polypropylene. The tip was then filled with inner
      reference solution containing SMX and chlorate (as interfering compound). The
      corresponding concentrations were studied for 1 * 10(-5) to 1 * 10(-10) and 1 *
      10(-3) to 1 * 10(-8)mol/L. The best condition allowed the detection of 5.92 ng/L
      (or 2.3 * 10(-8)mol/L) SMX for a sub-Nernstian slope of -40.3 mV/decade from 5.0
      * 10(-8) to 2.4 * 10(-5)mol/L. The described sensors were found promising devices
      for field applications. The good selectivity of the sensory materials together
      with a carefully selected composition for the inner reference solution allowed
      LODs near the nanomolar range. Both solid-contact and "pipette tip"-based sensors
      were successfully applied to the analysis of aquaculture waters.

PMID- 22465446
TI  - Graphene/quantum dot bionanoconjugates as signal amplifiers in stripping
      voltammetric detection of EpCAM biomarkers.
AB  - A sensitive electrochemical immunosensor for the detection of epithelial cell
      adhesion molecule (EpCAM) antigen, a common marker for tumors of epithelial
      origin, employing bionanoconjugates as signal-transduction labels has been
      developed. The bionanoconjugates were fabricated by carboxylation of the two
      dimensional graphene oxide nanosheets (GRs) and immobilizing streptavidin and
      amine-functionalized CdSe quantum dots (QDs) on carboxylated GRs via carbodiimide
      coupling chemistry, followed by the immunoreaction with the biotinylated
      secondary antibodies. Since carboxylated GRs have a higher density of active
      sites, it allows a large number of CdSe QDs to be immobilized onto the surface of
      the bionanoconjugates, and hence, enhance the sensitivity of the immunosensor.
      The method enabled detection limits of 100 fg/mL and 1 pg/mL (based on the S/N=3)
      in PBS buffer and serum samples, respectively, using anodic stripping
      voltammetric readout. The immunosensor showed a good selectivity,
      reproducibility, and long-storage stability, and may become a promising technique
      for the early detection of tumor biomarker in clinical/biological samples.

PMID- 22465447
TI  - Quantitative analysis of sialic acid on erythrocyte membranes using a
      photothermal biosensor.
AB  - The quantitative analysis of sialic acid (SA) at an erythrocyte membrane is
      becoming an important clinical parameter in diagnosing cancer and diabetes. In
      spite of such clinical importance, there are only a few, very expensive, time
      consuming and complicated quantifying methods established. To solve this problem,
      we demonstrate a novel and direct measurement technique for SA exposed to the
      cell membrane using a photothermal biosensing system in which the hemoglobin
      molecules in the erythrocyte absorb a specific wavelength of photons (532 nm) and
      convert it to a temperature change. For measuring the quantity of SA, we first
      modified the sensor surface of a micro-scaled thermometer using phenylboronic
      acid (PBA) containing a self-assembled monolayer (SAM) to capture the SA
      expressing erythrocytes. Second, the sensor surface was thoroughly washed, and
      when more SA was expressed, tighter association of erythrocytes to the biosensor
      was expected. Thirdly, blood sample changes in temperature, heated by the 532 nm
      wavelength laser, were measured by the bottom layer's micron sized platinum
      thermometer. The temperature changes from the erythrocytes captured on the sensor
      surface could be estimated by the amount of SA expressed on the erythrocyte
      membrane. This novel SA analysis system can solve the problems raised by
      conventional methods such as multiple enzyme reactions and a time consuming
      process. We expect that this system will help provide a new tool in the
      quantitative analysis of SA expression level for the diagnosis of diabetes and
      cancers.

PMID- 22465448
TI  - Optical diagnosis of laryngeal cancer using high wavenumber Raman spectroscopy.
AB  - We report the implementation of the transnasal image-guided high wavenumber (HW)
      Raman spectroscopy to differentiate tumor from normal laryngeal tissue at
      endoscopy. A rapid-acquisition Raman spectroscopy system coupled with a
      miniaturized fiber-optic Raman probe was utilized to realize real-time HW Raman
      (2800-3020 cm(-1)) measurements in the larynx. A total of 94 HW Raman spectra (22
      normal sites, 72 tumor sites) were acquired from 39 patients who underwent
      laryngoscopic screening. Significant differences in Raman intensities of
      prominent Raman bands at 2845, 2880 and 2920 cm(-1) (CH(2) stretching of lipids),
      and 2940 cm(-1) (CH(3) stretching of proteins) were observed between normal and
      cancer laryngeal tissue. The diagnostic algorithms based on principal components
      analysis (PCA) and linear discriminant analysis (LDA) together with the leave-one
      subject-out, cross-validation method on HW Raman spectra yielded a diagnostic
      sensitivity of 90.3% (65/72) and specificity of 90.9% (20/22) for laryngeal
      cancer identification. This study demonstrates that HW Raman spectroscopy has the
      potential for the noninvasive, real-time diagnosis and detection of laryngeal
      cancer at the molecular level.

PMID- 22465449
TI  - Bioelectrocatalytic detection of glycated hemoglobin (HbA1c) based on the
      competitive binding of target and signaling glycoproteins to a boronate-modified
      surface.
AB  - We developed an electrochemical glycated hemoglobin (HbA(1c)) biosensor for
      diagnosing diabetes in whole human blood based on the competitive binding
      reaction of glycated proteins. Until now, no studies have reported a simple and
      accurate electrochemical biosensor for the quantification of HbA(1c) in whole
      blood. This is because it is very difficult to correctly distinguish HbA(1c) from
      large amounts of hemoglobin and other components in whole blood. To detect
      glycated hemoglobin, we used electrodes modified with boronic acid, which forms a
      covalent bond between its diol group and the cis-diol group of the carbohydrate
      moiety of glycated proteins. For accurate HbA(1c) biosensing, we first removed
      blood components (except for hemoglobin) such as glycated proteins and blood
      glucose as they interfere with the boronate-based HbA(1c) competition analysis by
      reacting with the boronate-modified surface via a cis-diol interaction. After
      hemoglobin separation, target HbA(1c) and GOx at a predetermined concentration
      were reacted through a competition onto the boronate-modified electrode, allowing
      HbA(1c) to be detected linearly within a range of 4.5-15% of the separated
      hemoglobin sample (HbA(1c)/total hemoglobin). This range covers the required
      clinical reference range of diabetes mellitus. Hence, the proposed method can be
      used for measuring %HbA(1c) in whole human blood, and can also be applied to
      measuring the concentration of various glycated proteins that contain peripheral
      sugar groups.

PMID- 22465450
TI  - A WASO sub-group analysis of a 6-month study of eszopiclone 3 mg.
AB  - BACKGROUND: Insomnia marked by sleep maintenance difficulty is extremely
      prevalent. Yet, problems staying asleep have been relatively neglected as a
      research focus compared to problems falling asleep. Insomnia treatment studies
      typically have not required participants to have a problem specifically with
      sleep maintenance. It is possible that exclusion of such subjects limits the
      detection of treatment effects in the overall trial in general, and of effects on
      sleep maintenance specifically. In order to address these issues we conducted a
      post hoc analysis of a 6-month placebo-controlled trial in which there were no
      inclusion criteria that specified sleep maintenance difficulties to assess the
      variable effects of baseline wake time after sleep onset (WASO - the primary
      maintenance measure) on the efficacy of eszopiclone 3mg. METHODS: Patients
      diagnosed with chronic primary insomnia were randomized to eszopiclone 3mg
      (n=593) or placebo (n=195) nightly for six months. The present analyses of this
      study consisted of: (1) determination of the distribution of baseline WASO; (2)
      continuous analysis of the relationship between baseline WASO severity and drug
      placebo difference at month 1 and 6; and (3) categorical efficacy analyses of
      subgroups delimited by the following WASO thresholds: 0, 30, 45, 60, and 90 min.
      RESULTS: The baseline WASO distribution was: <= 30=32.2%; >0 to <= 45=41.5%; >30
      to <= 90=33.0%; >45 to <= 90=23.7%; >90=22.6%. A relationship between greater
      baseline WASO severity and a significantly greater drug-placebo difference in
      efficacy for WASO was evident in both continuous and categorical analyses.
      Eszopiclone was found to have significant sleep maintenance efficacy at each time
      point across the entire range of WASO severity studied. CONCLUSIONS: As
      illustrated in this analysis, a significant proportion of chronic insomnia
      patients in efficacy trials that select on the basis of sleep onset latency and
      total sleep time criteria may have normative-range WASO. However, even in the
      subgroup with minimal WASO there was a significant sleep maintenance effect. The
      absence of any sleep maintenance effect in a drug trial may reflect the inclusion
      of relatively many insomnia patients with no baseline WASO abnormality. However,
      treatments with therapeutic effects on sleep maintenance, can still demonstrate
      improvement in sleep maintenance, even in a population not selected for this type
      of sleep problem, if adequately powered. Future clinical trials intending to
      examine sleep maintenance should employ WASO selection criteria that would ensure
      sufficient power to detect a sleep maintenance effect. Drug-placebo difference
      increased as a function of baseline WASO severity, suggesting that eszopiclone's
      clinical effectiveness for insomnia may be enhanced in patients with more severe
      sleep maintenance symptoms.

PMID- 22465451
TI  - Functional capacity is a better predictor of coronary heart disease than
      depression or abnormal sleep duration in Black and White Americans.
AB  - OBJECTIVE: To assess whether functional capacity is a better predictor of
      coronary heart disease (CHD) than depression or abnormal sleep duration. METHODS:
      Adult civilians in the USA (n=29,818, mean age 48 +/- 18 years, range 18-85
      years) were recruited by a cross-sectional household interview survey using
      multistage area probability sampling. Data on chronic conditions, estimated
      habitual sleep duration, functional capacity, depressed moods, and
      sociodemographic characteristics were obtained. RESULTS: Thirty-five percent of
      participants reported reduced functional capacity. The CHD rates among White and
      Black Americans were 5.2% and 4%, respectively. Individuals with CHD were more
      likely to report extreme sleep durations (short sleep [<= 5h] or long sleep [>= 9
      h]; odds ratio [OR] 1.65, 95% confidence interval [CI] 1.38-1.97; P<0.0001), less
      likely to be functionally active (anchored by the ability to walk one-quarter of
      a mile without assistance [OR 6.27, 95% CI 5.64-6.98; P<0.0001]) and more likely
      to be depressed (OR 1.78, 95% CI 1.60-1.99; P<0.0001) than their counterparts. On
      multivariate regression analysis adjusting for sociodemographic factors and
      health characteristics, only functional capacity remained an independent
      predictor of CHD (OR 1.81, 95% CI 1.42-2.31; P<0.0001). CONCLUSION: Functional
      capacity was an independent predictor of CHD in the study population, whereas
      depression and sleep duration were not independent predictors.

PMID- 22465452
TI  - Exercise and the aging immune system.
AB  - Aging is associated with a decline in the normal functioning of the immune system
      that is described by the canopy term "immunosenescence". This contributes to
      poorer vaccine responses and the increased incidence of infection and malignancy
      seen in the elderly. Regular exercise has been associated with enhanced
      vaccination responses, lower numbers of exhausted/senescent T-cells, increased T
      cell proliferative capacity, lower circulatory levels of inflammatory cytokines
      ("inflamm-aging"), increased neutrophil phagocytic activity, lowered inflammatory
      response to bacterial challenge, greater NK-cell cytotoxic activity and longer
      leukocyte telomere lengths in aging humans, all of which indicate that habitual
      exercise is capable of regulating the immune system and delaying the onset of
      immunosenescence. This contention is supported by the majority of animal studies
      that report improved immune responses and outcomes to viral infections and
      malignancies due to exercise training. However, whether or not exercise can
      reverse, as well as prevent, immunosenescence is a contentious issue,
      particularly because most longitudinal exercise training studies do not report
      the same positive effects of exercise on immunity that have been widely reported
      in studies with a cross-sectional design. In this review, we summarize some of
      the known effects of exercise on immunosenescence, discuss avenues for future
      research, and provide potential mechanisms by which exercise may help rejuvinate
      the aging immune system.

PMID- 22465454
TI  - Transgenerational effects of early experience on behavioral, hormonal and gene
      expression responses to acute stress in the precocial chicken.
AB  - Stress during early life can profoundly influence an individual's phenotype.
      Effects can manifest in the short-term as well as later in life and even in
      subsequent generations. Transgenerational effects of stress are potentially
      mediated via modulation of the hypothalamic-pituitary-adrenal axis (HPA) as well
      as epigenetic mechanisms causing heritable changes in gene expression. To
      investigate these pathways we subjected domestic chicken (Gallus gallus) to
      intermittent social isolation for the first three weeks of life. The early life
      stress resulted in a dampened corticosterone response to restraint stress in
      affected birds and in their male offspring. Stress-specific genes, such as early
      growth response 1 (EGR1) and corticotropin releasing hormone receptor 1 (CRHR1),
      were upregulated immediately after restraint stress, but not under baseline
      conditions. Treatment differences in gene expression were also correlated across
      generations which indicate transgenerational epigenetic inheritance. In an
      associative learning test early stressed birds made more correct choices
      suggesting a higher coping ability in stressful situations. This study is the
      first to show transgenerational effects of early life stress in a precocial
      species by combining behavioral, endocrinological, and transcriptomic
      measurements.

PMID- 22465453
TI  - Social isolation impairs adult neurogenesis in the limbic system and alters
      behaviors in female prairie voles.
AB  - Disruptions in the social environment, such as social isolation, are distressing
      and can induce various behavioral and neural changes in the distressed animal. We
      conducted a series of experiments to test the hypothesis that long-term social
      isolation affects brain plasticity and alters behavior in the highly social
      prairie vole (Microtus ochrogaster). In Experiment 1, adult female prairie voles
      were injected with a cell division marker, 5-bromo-2'-deoxyuridine (BrdU), and
      then same-sex pair-housed (control) or single-housed (isolation) for 6 weeks.
      Social isolation reduced cell proliferation, survival, and neuronal
      differentiation and altered cell death in the dentate gyrus of the hippocampus
      and the amygdala. In addition, social isolation reduced cell proliferation in the
      medial preoptic area and cell survival in the ventromedial hypothalamus. These
      data suggest that long-term social isolation affects distinct stages of adult
      neurogenesis in specific limbic brain regions. In Experiment 2, isolated females
      displayed higher levels of anxiety-like behaviors in both the open field and
      elevated plus maze tests and higher levels of depression-like behavior in the
      forced swim test than controls. Further, isolated females showed a higher level
      of affiliative behavior than controls, but the two groups did not differ in
      social recognition memory. Together, our data suggest that social isolation not
      only impairs cell proliferation, survival, and neuronal differentiation in limbic
      brain areas, but also alters anxiety-like, depression-like, and affiliative
      behaviors in adult female prairie voles. These data warrant further investigation
      of a possible link between altered neurogenesis within the limbic system and
      behavioral changes.

PMID- 22465456
TI  - Restoration of sinus rhythm prior to catheter ablation of persistent atrial
      fibrillation: reverse remodeling or patient selection?

PMID- 22465457
TI  - Sympathetic innervation of the anterior left ventricular wall by the right and
      left stellate ganglia.
AB  - BACKGROUND: The sympathetic nervous system is thought to play a role in the
      genesis of ventricular tachyarrhythmias (VT). Left and added right cardiac
      sympathectomy have been shown to reduce the burden of arrhythmias in the setting
      of a VT storm. However, the contribution of the right stellate ganglion (RSG) and
      the left stellate ganglion (LSG) to the innervation of the anterior left
      ventricular (LV) wall is not well understood. OBJECTIVE: To evaluate the
      innervation of the anterior LV wall by the LSG and the RSG. METHODS: The heart
      and stellate ganglia were exposed via sternotomy in pigs with normal hearts (n =
      8). A 20-electrode catheter was placed on the anterior LV wall to record
      activation recovery interval (ARI), a surrogate measure of action potential
      duration. A microdialysis catheter was inserted in a similar location to sample
      interstitial norepinephrine (NE) content. ARI and NE measurements were recorded
      at baseline and during LSG and RSG stimulation. RESULTS: LSG stimulation
      shortened ARI by 17.1% +/- 10.5% (mean +/- standard error), while RSG stimulation
      shortened ARI by 42.1% +/- 15.7%, P = .04 (LSG vs RSG). LSG stimulation increased
      interstitial NE levels by 200% +/- 65%, while RSG stimulation increased the NE
      content by 260% +/- 40% (P = .012). LSG stimulation increased dispersion in ARI
      from 376.0 +/- 83.7 ms(2) to 1242.5 +/- 566 ms(2) (P = .03) and caused
      ventricular fibrillation in 2 pigs. During RSG stimulation, dispersion increased
      from 419 +/- 65.8 to 474.8 +/- 81 ms(2) (P = .4). CONCLUSIONS: Both the LSG and
      the RSG provide significant innervation to the anterior LV wall as demonstrated
      by both ARI shortening and NE concentrations. LSG stimulation significantly
      increases ARI dispersion. This study provides mechanistic insight into the
      beneficial effects of left sympathectomy and the additional role of right
      sympathectomy in reducing arrhythmias in patients with anterior myocardial scars
      and VT storm.

PMID- 22465455
TI  - Prenatal programing: at the intersection of maternal stress and immune
      activation.
AB  - Exposure to prenatal insults such as maternal stress and pathogenic infections
      has been associated with an increased risk for neurodevelopmental disorders. The
      mechanisms by which these programing events occur likely involve complex
      interactions between the maternal hormonal milieu, the placenta, and the
      developing fetus, in addition to compounding factors such as fetal sex and
      gestational stage of development. Despite the diverse biological processes
      involved, examination of common pathways in maternal stress and immune activation
      offers intriguing possibilities for elucidation of mechanistic insight. Further,
      the endocrine and sex-specific placenta is a tissue poised to be a key mediator
      in fetal programing, located at the intersection of the maternal and embryonic
      environments. In this review, we will discuss the potential shared mechanisms of
      maternal stress and immune pathway activation, with a particular focus on the
      important contribution and role of the placenta.

PMID- 22465458
TI  - Focal impulse and rotor modulation ablation of sustaining rotors abruptly
      terminates persistent atrial fibrillation to sinus rhythm with elimination on
      follow-up: a video case study.

PMID- 22465459
TI  - Functional topography of primary emotion processing in the human cerebellum.
AB  - The cerebellum has an important role in the control and coordination of movement.
      It is now clear, however, that the cerebellum is also involved in neural
      processes underlying a wide variety of perceptual and cognitive functions,
      including the regulation of emotional responses. Contemporary neurobiological
      models of emotion assert that a small set of discrete emotions are mediated
      through distinct cortical and subcortical areas. Given the connectional
      specificity of neural pathways that link the cerebellum with these areas, we
      hypothesized that distinct sub-regions of the cerebellum might subserve the
      processing of different primary emotions. We used functional magnetic resonance
      imaging (fMRI) to identify neural activity patterns within the cerebellum in 30
      healthy human volunteers as they categorized images that elicited each of the
      five primary emotions: happiness, anger, disgust, fear and sadness. In support of
      our hypothesis, all five emotions evoked spatially distinct patterns of activity
      in the posterior lobe of the cerebellum. We also detected overlaps between
      cerebellar activations for particular emotion categories, implying the existence
      of shared neural networks. By providing a detailed map of the functional
      topography of emotion processing in the cerebellum, our study provides important
      clues to the diverse effects of cerebellar pathology on human affective function.

PMID- 22465460
TI  - Hyperbaric oxygen therapy: can it prevent irradiation-induced necrosis?
AB  - Radiosurgery is an important non-invasive procedure for the treatment of tumors
      and vascular malformations. However, in addition to killing target tissues,
      cranial irradiation induces damage to adjacent healthy tissues leading to
      neurological deterioration in both pediatric and adult patients, which is poorly
      understood and insufficiently treatable. To minimize irradiation damage to
      healthy tissue, not the optimal therapeutic irradiation dose required to
      eliminate the target lesion is used but lower doses. Although the success rate of
      irradiation surgery is about 95%, 5% of patients suffer problems, most commonly
      neurological, that are thought to be a direct consequence of irradiation-induced
      inflammation. Although no direct correlation has been demonstrated, the
      appearance and disappearance of inflammation that develops following irradiation
      commonly parallel the appearance and disappearance of neurological side effects
      that are associated with the neurological function of the irradiated brain
      regions. These observations have led to the hypothesis that brain inflammation is
      causally related to the observed neurological side effects. Studies indicate that
      hyperbaric oxygen therapy (HBOT) applied after the appearance of irradiation
      induced neurological side effects reduces the incidence and severity of those
      side effects. This may result from HBOT reducing inflammation, promoting
      angiogenesis, and influencing other cellular functions thereby suppressing events
      that cause the neurological side effects. However, it would be significantly
      better for the patient if rather than waiting for neurological side effects to
      become manifest they could be avoided. This review examines irradiation-induced
      neurological side effects, methods that minimize or resolve those side effects,
      and concludes with a discussion of whether HBOT applied following irradiation,
      but before manifestation of neurological side effects may prevent or reduce the
      appearance of irradiation-induced neurological side effects.

PMID- 22465461
TI  - Coupling biomarkers and drug action for neurodegenerative disease therapies: does
      the nose know?: Commentary on Sattler et al.: human nasal olfactory epithelium as
      a dynamic marker for CNS therapy development.

PMID- 22465462
TI  - Low-frequency modulated quadratic and cubic distortion product otoacoustic
      emissions in humans.
AB  - Previous studies have used low-frequency tones to modulate distortion product
      otoacoustic emissions (DPOAEs). The cubic DPOAE (CDPOAE) is mostly chosen because
      amplitudes sufficient for modulation can be evoked with moderate sound pressure
      levels. Quadratic DPOAEs (QDPOAEs) however, are more sensitive to minute changes
      of the cochlear operating point (OP) and are better suited to assess changes of
      the cochlear OP. Here, we compare the properties of low-frequency (30 Hz, 80-120
      dB SPL) modulated CDPOAE and QDPOAEs evoked with f(2) = 2 and 5 kHz in human
      subjects with normal hearing. The modulation depth was quantified with the
      modulation index (MI), a measure which considers both amplitude and phase.
      Modulated CDPOAEs evoked with f(2) = 2 kHz have amplitude maxima at the zero
      crossings and amplitude minima at the extremes of the biasing tone (BT) which
      correlate positively with the BT level. CDPOAEs evoked with f(2) = 5 kHz were
      recorded during biasing in exactly the same way as described before. At the
      highest BT levels used (120 dB SPL), very little modulation could be detected.
      Not only the depth, but also the shape of the QDPOAE modulation pattern is
      correlated with the BT level. At moderate BT levels (about 90-100 dB SPL) QDPOAEs
      evoked with f(2) = 5 kHz show one amplitude notch around the zero crossing of the
      positive going flank of the BT (a single modulation pattern). At and above a BT
      level of about 105 dB SPL, the pattern reverses and shows a double modulation
      pattern. At the highest BT level used (120 dB SPL), quadratic MIs exceed cubic
      MIs (2.0 +/- 0.5 and 0.97 +/- 0.06, respectively). Patterns of low-frequency
      modulated QDPOAEs in humans are similar to the modulation seen in animal studies
      and as predicted by mathematical models. Human low-frequency modulated QDPOAEs
      are ideally suited to estimate cochlear OP shifts because of their high
      sensitivity to the OP shift.

PMID- 22465463
TI  - Automatic left ventricle segmentation in cardiac MRI using topological stable
      state thresholding and region restricted dynamic programming.
AB  - RATIONALE AND OBJECTIVES: Segmentation of the left ventricle (LV) is very
      important in the assessment of cardiac functional parameters. The aim of this
      study is to develop a novel and robust algorithm which can improve the accuracy
      of automatic LV segmentation on short-axis cardiac magnetic resonance images
      (MRI). MATERIALS AND METHODS: The database used in this study consists of 45
      cases obtained from the Sunnybrook Health Sciences Centre. The 45 cases contain
      12 ischemic heart failures, 12 non-ischemic heart failures, 12 LV hypertrophies,
      and 9 normal cases. Three key techniques are developed in this segmentation
      algorithm: 1) topological stable-state thresholding method is proposed to refine
      the endocardial contour, 2) an edge map with non-maxima gradient suppression
      approach, and 3) a region-restricted technique that is proposed to improve the
      dynamic programming to derive the epicardial boundary. RESULTS: The validation
      experiments were performed on a pool of data sets of 45 cases. For both endo- and
      epicardial contours of our results, percentage of good contours is about 91%, the
      average perpendicular distance is about 2 mm, and the overlapping dice metric is
      about 0.91. The regression and determination coefficient for the experts and our
      proposed method on the ejection fraction is 1.05 and 0.9048, respectively; they
      are 0.98 and 0.8221 for LV mass. CONCLUSIONS: An automatic method using
      topological stable-state thresholding and region restricted dynamic programming
      has been proposed to segment left ventricle in short-axis cardiac MRI. Evaluation
      results indicate that the proposed segmentation method can improve the accuracy
      and robust of left ventricle segmentation. The proposed segmentation approach
      shows the better performance and has great potential in improving the accuracy of
      computer-aided diagnosis systems in cardiovascular diseases.

PMID- 22465464
TI  - The effect of Zafirlukast on capsule formation in post-radiation silicone
      implants.
AB  - Currently, breast cancer represents the most common indication for mastectomy
      with negative influence on personal perception, sexuality and partnership. Since
      the introduction of breast implants, silicone, and saline breast implantation
      have become one of the most common procedures performed by plastic surgeons, not
      only for aesthetic reasons but also for reconstructive purposes. These women will
      ultimately be faced with the prospect of capsular contracture. This is especially
      true in patients receiving radiation therapy, where irradiation increases the
      risk of complications, capsular contracture and may compromise a favorable
      aesthetic result. Despite the capsular contracture is the most common
      complication for both aesthetic and reconstructive breast surgery, the treatment
      have remained unsolved. Leukotriene antagonists (LTRAs) have emerged as effective
      prophylactic agents in the management of reactive airway diseases, and recently
      they have used as an off label prophylactic agent against the capsular
      contracture after breast augmentation. However up to now there is no any
      experimental research or clinical study in the medical literature about the
      effect of Zafirlukast on the capsular formation around irradiated silicone
      implants.

PMID- 22465466
TI  - Myopia and iris colour: a possible connection?
AB  - Myopia is a common ocular disease in the world. Its prevalence has increased
      rapidly worldwide, especially in some East-Asian countries. Genetic factors and
      environmental factors both affect myopia's onset and its progress. Iris colour is
      an important characteristic of a person. It is a possible risk factor for myopia
      by affecting the amount and the colour of light entering eyes. The study of iris
      colour may contribute to the understanding of myopia mechanism and provide good
      suggestive evidence for studies on other eye diseases. In this article, the
      possible connection between myopia and iris colour is proposed. Approaches to
      dissect any link are suggested.

PMID- 22465465
TI  - The defence architecture of the superficial cells of the oral mucosa.
AB  - The oral epithelium together with the saliva and its components forms a complex
      structure which is the first line of defence in the oral cavity. The surface of
      superficial cells of the oral epithelium contains ridge-like folds, microplicae
      (MPL), which are typical of the surfaces of areas covered with protective mucus.
      The role of MPL seen on the upper surface of the oral epithelial cells is still
      unknown. The salivary mucus gel performs a protective diffusion membrane against
      harmful substances and this membrane is built up by epithelial cells covered by a
      highly hydrated and viscous gel, where mucins constitute the scaffold. The
      interaction between the MPL-structure and the mucins is shown in cornea, so that
      mucins are expressed on the tips of the MPL of the epithelial cells. We
      hypothesized that the MPL architecture of oral superficial epithelial cells
      provides the underlying basis for mucins's protective function as well as in
      ocular surface. The salivary mucous barrier is required to protect the
      superficial cells and the MPL-structure together with membrane anchored mucin
      binding protein (MBP) forms the ground to this mucous barrier. So, oral mucosal
      barrier complex (OMBC) contains both the MBP-mucin - complex and the MPL
      structure of the superficial cells. In the future, studies of the alterations of
      the salivary mucins and that of the MPL-structure may yield therapeutic
      opportunities for burning mouth syndrome and perhaps for mucositis causing by
      irradiation. Focus on cell surface microplication and mucins in oral mucosal
      biology and oral mucosal diseases is a promising avenue for future research in
      several ways.

PMID- 22465467
TI  - Anorexia nervosa, autoimmunity and the hygiene hypothesis.
AB  - The hypothesis proposed is that anorexia nervosa (AN) is an autoimmune disease
      caused by delayed exposure to common micro-organisms in which auto-antibodies to
      regulatory peptides and hypothalamic neurons, which cross react with microbial
      antigens, disturb appetite and lead to decreased intake of food. IgG, IgA and IgM
      auto-antibodies to a range of regulatory peptides concerned with appetite and
      mood are found in patients with AN. The regulatory peptides show sequence
      homology with common micro-organisms of the microbial flora. Auto-antibodies to
      alpha melanocyte stimulating hormone (alphaMSH) are positively correlated with AN
      psychopathology. But patients with bulimia nervosa (BN) and normal healthy
      controls also have a similar range of auto-antibodies at comparable levels. The
      incidence of AN is rising in developed countries, the disease is more common in
      females than in males, the peak incidence is in the teenage years, there is
      seasonal variation in the month of birth and the disease is more common in higher
      socio-economic groups. These are all features which are consistent with the
      hygiene hypothesis. But there is no evidence that the disease is more common in
      first born than in later born children. There is a paucity of data on early life
      events such as attendance at nursery and exposure to pets. Genetic factors are
      important but the data on major histocompatibility complex (MHC) gene
      polymorphisms are contradictory. The epidemiological and serological data are
      consistent with the hypothesis under investigation but key questions in relation
      to the hygiene hypothesis have not been posed. A large case control study of AN
      epidemiology is indicated. MHC gene polymorphisms should be assessed. There is,
      however, sufficient evidence to justify a trial of pooled immunoglobulin therapy
      in patients with life threatening AN.

PMID- 22465468
TI  - Facets of Pavlovian and operant extinction.
AB  - Research on extinction is of fundamental importance in both Pavlovian and operant
      approaches to the experimental analysis of learning. Although these approaches
      are often motivated by different empirical and theoretical questions, extinction
      has emerged as a research area in which common themes unite the two approaches.
      In this review, we focus on some common considerations in the analysis of
      Pavlovian and operant extinction. These include methodological challenges and
      interpretational issues in analyzing behavior during and after extinction. We
      consider the different roles that theory has played in the development of
      research on extinction in these preparations and conclude with some attention to
      applications of extinction.

PMID- 22465470
TI  - Renewal and reinstatement of the conditioned but not the unconditioned response
      following habituation of the unconditioned stimulus.
AB  - Research on the inhibition of learned fear currently relies almost exclusively on
      one specific procedure, namely extinction of the conditioned stimulus (CS).
      Importantly, however, learned fear responses can be reduced by a number of other
      procedures, including habituation of the unconditioned stimulus (US). We recently
      demonstrated that reductions in learned fear following US habituation, like CS
      extinction, were subject to both renewal and reinstatement (Storsve et al.,
      2010). The present study further investigates the associative and non-associative
      processes shared between habituation and extinction. Given that habituation is
      typically context-independent (Mackintosh, 1987), in the present study we
      directly compared renewal and reinstatement of both a conditioned response (CR;
      freezing) and an unconditioned response (UR; startle) following habituation. It
      was found that the reduction in conditioned freezing resulting from habituation
      was context specific (i.e., a change in context led to a renewal of the
      conditioned fear response; Experiment 1) and was attenuated when a pre-test shock
      was given (i.e., reinstatement of conditioned fear was observed; Experiment 2).
      In contrast, habituation of an unconditioned response elicited by the US (i.e., a
      startle response) was unaffected by either a change in test context or
      administration of a pre-test shock. This dissociation in the effects of
      habituation on learned and unlearned responses is discussed in relation to
      theories of fear extinction.

PMID- 22465469
TI  - A parametric analysis of factors affecting acquisition and extinction of
      contextual fear in C57BL/6 and DBA/2 mice.
AB  - Behavioral analyses of genetically modified and inbred strains of mice have
      revealed neural systems and molecules that are involved in memory formation. Many
      of these studies have examined memories that form in contextual fear
      conditioning, in which an organism learns that a particular context signals the
      occurrence of a footshock. During fear extinction, nonreinforced exposure to the
      context results in the loss of the conditioned fear response. The study of
      extinction has been instrumental for behavioral and molecular theories of memory.
      However, many of the transgenic, knockout, and inbred strains of mice that have
      been widely studied in memory have behavioral deficits in contextual fear
      conditioning, which makes the study of extinction in these mice particularly
      challenging. Here we explore several strategies for studying extinction in
      C57BL/6 and DBA/2 mice, two strains known to differ in contextual fear
      conditioning. First, we attempt to equate performance prior to extinction through
      several extensive conditioning protocols. Second, we examine extinction in
      subsets of mice matched for initial levels of context conditioning. Third, we
      examine within-strain effects of variables known to affect extinction.
      Differences between the strains persisted across extensive conditioning and
      extinction protocols, but both strains were sensitive to session duration and
      context manipulations during extinction. We describe the implications of our
      results for behavioral and neurobiological approaches to extinction, and we
      examine the general challenges in studying extinction in subjects that differ in
      learning or performance prior to extinction.

PMID- 22465471
TI  - Molecular characterisation of a novel cassava associated circular ssDNA virus.
AB  - The application of sequence non-specific rolling circle amplification of circular
      single stranded (ss) DNA molecules to viral metagenomics has facilitated the
      discovery in various ecosystems of what is probably a diverse array of novel
      ssDNA viruses. Here we describe a putative novel ssDNA virus (at a genome level),
      cassava associated circular DNA virus (CasCV), isolated from cassava leaf samples
      infected with the fungi Collectotrichum and Plectosphaerella. CasCV has a
      circular ambisense genome and shares significant genome similarities with
      Sclerotinia sclerotiorum hypovirulence-associated DNA virus 1 (SsHADV-1),
      Mosquito VEM virus SDBVL and Meles meles faecal virus (MmFV). The CasCV genome
      (2220 nt) has three large open reading frames. While it is probable that one of
      these encodes a capsid protein, the other two probably express a replication
      associated protein (Rep) following the removal of an intron such as that found in
      the Rep encoding genes of some geminiviruses. This Rep would contain four
      conserved rolling circle replication (RCR) related motifs that have previously
      been identified in geminivirus, circovirus and nanovirus Reps. Given both that
      the CasCV Rep and CP share 62.7% and 39.8% amino acid identity respectively with
      the Rep and CP of SsHADV-1, and that CasCV was discovered associated with cassava
      infecting fungi, we suggest that CasCV should be classified within the mycovirus
      taxonomic family. However, host range studies using infectious clones will be
      required to demonstrate the novel virus' likely origin and actual host species.

PMID- 22465473
TI  - Clothing choices, weight, and trait self-objectification.
AB  - The present study aimed to assess the link between clothing choice and aspects of
      body image. Participants were 112 female undergraduate students who completed a
      questionnaire containing a measure of clothing functions, as well as BMI, self
      classified weight, and trait self-objectification. Results indicated that BMI and
      self-classified weight were positively correlated with the choice of clothes for
      camouflage. Self-objectification was positively correlated with choice of clothes
      for fashion, and negatively correlated with choosing clothes for comfort. It was
      concluded that clothing represents an important but neglected aspect of
      contemporary women's management of their body's appearance.

PMID- 22465472
TI  - Inhalation of sulfur mustard causes long-term T cell-dependent inflammation:
      possible role of Th17 cells in chronic lung pathology.
AB  - Sulfur mustard (SM) is a highly toxic chemical warfare agent that remains a
      threat to human health. The immediate symptoms of pulmonary distress may develop
      into chronic lung injury characterized by progressive lung fibrosis, the major
      cause of morbidity among the surviving SM victims. Although SM has been intensely
      investigated, little is known about the mechanism(s) by which SM induces chronic
      lung pathology. Increasing evidence suggests that IL-17(+) cells are critical in
      fibrosis, including lung fibrotic diseases. In this study we exposed F344 rats
      and cynomolgus monkeys to SM via inhalation and determined the molecular and
      cellular milieu in their lungs at various times after SM exposure. In rats, SM
      induced a burst of pro-inflammatory cytokines/chemokines within 72 h, including
      IL-1beta, TNF-alpha, IL-2, IL-6, CCL2, CCL3, CCL11, and CXCL1 that was associated
      with neutrophilic infiltration into the lung. At 2 wks and beyond (chronic
      phase), lymphocytic infiltration and continued elevated expression of
      cytokines/chemokines were sustained. TGF-beta, which was undetectable in the
      acute phase, was strongly upregulated in the chronic phase; these conditions
      persisted until the animals were sacrificed. The chronic phase was also
      associated with myofibroblast proliferation, collagen deposition, and presence of
      IL-17(+) cells. At >=30 days, SM inhalation promoted the accumulation of IL-17(+)
      cells in the inflamed areas of monkey lungs. Thus, SM inhalation causes acute and
      chronic inflammatory responses; the latter is characterized by the presence of
      TGF-beta, fibrosis, and IL-17(+) cells in the lung. IL-17(+) cells likely play an
      important role in the pathogenesis of SM-induced lung injury.

PMID- 22465474
TI  - Downregulation of IRS2 in myelodysplastic syndrome: a possible role in impaired
      hematopoietic cell differentiation.
AB  - Insulin receptor substrate 2 (IRS2) is an adaptor protein that associates with
      the receptor of erythropoietin, insulin-like growth factor 1 and thrombopoietin;
      however, its role is not known in myelodysplasia. We, herein, report a
      significantly lower IRS2 expression in MDS cells, compared to normal cells. IRS2
      expression was reduced in high-risk, compared to low-risk disease, and positively
      correlated with neutrophil and platelet counts. IRS2 was upregulated during
      erythroid differentiation of CD34(+) cells from normal donors and low-risk MDS
      patients and also during erythroid, granulocytic and megakaryocytic
      differentiation in cell lines. These results suggest that defective IRS2
      expression plays a role in the impaired hematopoietic cell differentiation in
      MDS.

PMID- 22465475
TI  - Neglect: a multisensory deficit?
AB  - Neglect is a neurological syndrome characterised by a lack of conscious
      perception of events localised in the contralesional side of space. Here, we
      consider the possible multisensory nature of this disorder, critically reviewing
      the literature devoted to multisensory manifestations and processing in neglect.
      Although its most striking manifestations have been observed in the visual
      domain, a number of studies demonstrate that neglect can affect virtually any
      sensory modality, in particular touch and audition. Furthermore, a few recent
      studies have reported a correlation in severity between visual and non-visual
      neglect-related deficits evaluated in the same patients, providing some
      preliminary support for a multisensory conception of neglect. Sensory stimulation
      and sensorimotor adaptation techniques, aimed at alleviating neglect, have also
      been shown to affect several sensory modalities, including some that were not
      directly affected by the intervention. Finally, in some cases neglect can bias
      multisensory interactions known to occur in healthy individuals, leading to
      abnormal behaviour or uncovering multisensory compensation mechanisms. This
      evidence, together with neurophysiological and neuroimaging data revealing the
      multisensory role played by the areas that are most commonly damaged in neglect
      patients, seems to speak in favour of neglect as a multisensory disorder.
      However, since most previous studies were not conducted with the specific purpose
      of systematically investigating the multisensory nature of neglect, we conclude
      that more research is needed to appropriately assess this question, and suggest
      some methodological guidelines that we hope will help clarify this issue. At
      present, the conception of neglect as a multisensory disorder remains a promising
      working hypothesis that may help define the pathophysiology of this syndrome.

PMID- 22465477
TI  - Analysis of responses to glyceryl trinitrate and sodium nitrite in the intact
      chest rat.
AB  - Responses to glyceryl trinitrate/nitroglycerin (GTN), S-nitrosoglutathione
      (GSNO), and sodium nitrite were compared in the intact chest rat. The iv
      injections of GTN, sodium nitrite, and GSNO produced dose-dependent decreases in
      pulmonary and systemic arterial pressures. In as much as cardiac output was not
      reduced, the decreases in pulmonary and systemic arterial pressures indicate that
      GTN, sodium nitrite, and GSNO have significant vasodilator activity in the
      pulmonary and systemic vascular beds in the rat. Responses to GTN were attenuated
      by cyanamide, but not allopurinol, whereas responses to nitrite formed by the
      metabolism of GTN were attenuated by allopurinol and cyanamide. The results with
      allopurinol and cyanamide suggest that only mitochondrial aldehyde dehydrogenase
      is involved in the bioactivation of GTN, sodium nitrite, and GSNO, whereas both
      pathways are involved in the bioactivation of nitrite anion in the intact rat.
      The comparison of vasodilator activity indicates that GSNO and GTN are more than
      1000-fold more potent than sodium nitrite in decreasing pulmonary and systemic
      arterial pressures in the rat. Following administration of 1H-[1,2,4]
      oxadizaolo[4,3-]quinoxaline-1-one (ODQ), responses to GTN were significantly
      attenuated, indicating that responses are mediated by the activation of soluble
      guanylyl cyclase. These data suggest that the reduction of nitrite to nitric
      oxide formed from the metabolism of GTN, cannot account for the vasodilator
      activity of GTN in the intact rat and that another mechanism; perhaps the
      formation of an S-NO, may mediate the vasodilator response to GTN in this
      species.

PMID- 22465478
TI  - WT1 and Sox11 regulate synergistically the promoter of the Wnt4 gene that encodes
      a critical signal for nephrogenesis.
AB  - Wnt4, a member of the Wnt superfamily of signaling molecules, is critical for
      mammalian kidney development, since nephrogenesis fails in its absence, while
      Wnt4 signaling induces mesenchyme-to-epithelium transition and associated
      tubulogenesis in the uninduced mesenchymal cells in the classic transfilter
      model. The factors that promote Wnt4 gene expression during kidney development
      are largely unknown, however. We addressed the upstream regulators of the Wnt4
      gene and describe here the transcription factors WT1 and Sox11 as candidate
      molecules in the control of gene expression. We found that WT1/Sox11 regulate
      Wnt4 promoter expression in a synergistic fashion in an embryonic kidney
      mesenchyme-derived cell line model. The transcription complex containing
      WT1/Sox11 was immunoprecipitated from embryonic kidney cells with Sox11
      antibodies, suggesting their presence in the same complex. Dominant negative
      forms of WT1, namely P129L and F154S mutants, inhibited Wnt4 expression, but this
      inhibition was not influenced by the presence of wild-type Sox11. The mutant WT1
      forms were similarly incapable of interacting with Sox11, as judged by reporter
      studies. The spatio-temporal expression pattern of wt1 and sox11 overlaps with
      that of Wnt4 in the early Xenopus pronephros. Morpholino-mediated knockdown of
      either wt1 or sox11 inhibited Wnt4 expression in the prospective pronephros of
      the Xenopus embryos. We propose that Sox11 represents a synergistic factor for
      WT1 in regulating the Wnt4 gene expression that is critical for nephrogenesis
      during kidney ontogeny.

PMID- 22465476
TI  - Myoglobin and mitochondria: a relationship bound by oxygen and nitric oxide.
AB  - Since their initial discovery over a century ago, our knowledge of the functions
      of myoglobin and the mitochondrion has gradually evolved. The mitochondrion, once
      thought to be solely responsible for energy production, is now known to be an
      integral redox and apoptotic signal transducer within the cell. Likewise,
      myoglobin, traditionally thought of only as an oxygen store, has emerged as a
      physiological catalyst that can modulate reactive oxygen species levels,
      facilitate oxygen diffusion and scavenge or generate nitric oxide (NO) depending
      on oxygen tensions within the cell. By virtue of its unique ability to regulate
      O(2) and NO levels within the cell, myoglobin can modulate mitochondrial function
      in energy-demanding tissues such as the beating heart and exercising muscle. In
      this review, we present the conventional functions of myoglobin and mitochondria,
      and describe how these roles have been reassessed and advanced, particularly in
      the context of NO and nitrite signaling. We present the mechanisms by which
      mitochondria and myoglobin regulate one another within the cell through their
      interactions with NO and oxygen and discuss the implications of these
      interactions in terms of health and disease.

PMID- 22465479
TI  - Neurotrophins and cell death.
AB  - The neurotrophins - NGF, BDNF, NT-3 - are secreted proteins that play a major
      role in neuron survival, differentiation and axon wiring toward target
      territories. They do so by interacting with their main tyrosine kinase receptors
      TrkA, TrkB, TrkC and p75(NTR). Even though there is a general consensus on the
      view that neurotrophins are survival factors, there are two fundamentally
      different views on how they achieve this survival activity. One prevailing view
      is that all neurons and more generally all normal cells are naturally committed
      to die unless a survival factor blocks this death. This death results from the
      engagement of a "default" apoptotic cell program. The minority report supports,
      on the opposite, that neurotrophin withdrawal is associated with an active signal
      of cell death induced by unbound dependence receptors. We will discuss here how
      neurotrophins regulate cell death and survival and how this has implications not
      only during nervous system development but also during cancer progression.

PMID- 22465480
TI  - Glomerular endothelium: a porous sieve and formidable barrier.
AB  - The glomerular capillary endothelium is highly specialized to support the
      selective filtration of massive volumes of plasma. Filtration is driven by
      Starling forces acting across the glomerular capillary wall, and depends on its
      large surface area and extremely high water permeability. Glomerular endothelial
      cells are extremely flat and perforated by dense arrays of trans-cellular pores,
      the fenestrae. This phenotype is critical for the high glomerular water
      permeability and depends on podocyte-derived VEGF, as well as TGF-beta.
      Endothelial cell-derived PDGFB, in turn, is necessary for the establishment of
      mesangial cells, which sculpt the glomerular loop structure that underlies the
      large filtration surface area. In pre-eclampsia, inhibition of the VEGF- and TGF
      beta signaling pathways leads to endothelial swelling and loss of fenestrae,
      reducing the glomerular filtration rate. Similarly, in the thrombotic
      microangiopathies, glomerular endothelial cell injury coupled with inappropriate
      VWF activation leads to intracapillary platelet aggregation and loss of the flat,
      fenestrated phenotype, thus reducing the glomerular filtration rate. Normally, a
      remarkably small fraction of albumin and other large plasma proteins passes
      across the glomerular capillary wall despite the massive filtration of water and
      small solutes. An elaborate glycocalyx, which covers glomerular endothelial cells
      and their fenestrae forms an impressive barrier that, together with other
      components of the glomerular capillary wall, prevents loss of plasma proteins
      into the urine. Indeed, microalbuminuria is a marker for endothelial glycocalyx
      disruption, and most forms of glomerular endothelial cell injury including pre
      eclampsia and thrombotic microangiopaties can cause proteinuria.

PMID- 22465481
TI  - High-throughput species identification of enterococci using pyrosequencing.
AB  - Here we report the development and validation of an automated high-throughput
      pyrosequencing-based method for the reliable identification of isolated
      Enterococcus species. This method exploits the discrete species-specificity of
      hypervariable groES-EL spacer region and utilizes a universal dispensation order
      optimized for a wide range of Enterococcus species.

PMID- 22465482
TI  - Discrepancy between patients' use of and health providers' familiarity with CAM.
AB  - OBJECTIVE: To compare patients' complementary and alternative medicine (CAM) use
      and physicians' familiarity with certain CAM modalities in the same setting and
      to assess patient-provider dialogue about patients' CAM use. METHODS: An
      observational survey study with convenience sampling at ambulatory family
      medicine clinics in two Texas cities. A total of 69 healthcare providers and 468
      patients completed the surveys. Patients' surveys assessed use of 27 CAM
      therapies, perception of CAM use and interaction with providers. Providers'
      survey assessed perception and attitude toward CAM use. RESULTS: CAM modalities
      most used by the patients are not those modalities that providers best
      understood. Of the 330 patients (70%) who responded to the relevant questions
      about discussing CAM, 44.5% reported never having discussed CAM use with their
      providers. Binomial logistic regression revealed no link between age, gender or
      ethnicity for discussing CAM with providers. College-educated patients (adjust
      OR=2.8, 95%CI=1.3-6.0) and US citizens were both about three times more likely to
      discuss CAM than their counterparts. CONCLUSION: Lack of knowledge and
      unfamiliarity with CAM modalities might prevent important patient-provider
      discussions. PRACTICE IMPLICATIONS: Providers should use existing resources and
      encourage a bilateral dialogue that involves transferring of information and
      assisting patients in decisions making about CAM use and health care.

PMID- 22465483
TI  - The challenges of facilitating primary healthcare discussions on traditional,
      complementary and alternative medicine for childhood eczema: piloting a
      computerized template.
AB  - OBJECTIVE: Healthcare practitioners (HCPs) experience barriers to changing
      routine consultation practice. Communication and recording of traditional,
      complementary and alternative medicines (TCAM) is inadequate. This pilot study
      explored the challenges of implementing a computerized template in primary care
      to facilitate communication on TCAM for paediatric eczema. METHODS: A
      computerized template to record TCAM use, with links to evidence-based TCAM
      databases, was designed, based on qualitative research with patients and HCPs.
      Four London general practices implemented the template integrated with usual
      practice. Twelve focus groups during the 6 month study period explored HCPs'
      knowledge, communication and information sources regarding TCAM and perceived
      barriers to template implementation. RESULTS: HCPs were initially enthusiastic
      about discussing TCAM, for improving communication and understanding patient's
      choices, but the template was used in under a third of consultations. HCPs were
      surprised at low TCAM use (10%) and lack of correlation with eczema or ethnicity.
      Reported barriers were time and remembering, due to busy, target-driven practice.
      CONCLUSION: HCPs recognize the importance of discussing TCAM use for childhood
      eczema, and potential benefits for HCP-patient communication. PRACTICE
      IMPLICATIONS: Future tools to facilitate TCAM discussion should prioritise use of
      existing IT systems and address barriers to use, especially lack of time.

PMID- 22465484
TI  - Decision making and coping in healthcare: the Coping in Deliberation (CODE)
      framework.
AB  - OBJECTIVE: To develop a framework of decision making and coping in healthcare
      that describes the twin processes of appraisal and coping faced by patients
      making preference-sensitive healthcare decisions. METHODS: We briefly review the
      literature for decision making theories and coping theories applicable to
      preference-sensitive decisions in healthcare settings. We describe first decision
      making, then coping and finally attempt to integrate these processes by building
      on current theory. RESULTS: Deliberation in healthcare may be described as a six
      step process, comprised of the presentation of a health threat, choice, options,
      preference construction, the decision itself and consolidation post-decision.
      Coping can be depicted in three stages, beginning with a threat, followed by
      primary and secondary appraisal and ultimately resulting in a coping effort.
      CONCLUSIONS: Drawing together concepts from prominent decision making theories
      and coping theories, we propose a multidimensional, interactive framework which
      integrates both processes and describes coping in deliberation. PRACTICE
      IMPLICATIONS: The proposed framework offers an insight into the complexity of
      decision making in preference-sensitive healthcare contexts from a patient
      perspective and may act as theoretical basis for decision support.

PMID- 22465485
TI  - Genome scan of the mitten crab Eriocheir sensu stricto in East Asia: population
      differentiation, hybridization and adaptive speciation.
AB  - We examine the genetic structure and evolutionary history of the mitten crab
      Eriocheir sensu stricto in East Asia by employing a genome scan - amplified
      fragment length polymorphism. Population analysis reveals three divergent clades
      in Eriocheir s. s., which dominate the East China Sea-Yellow Sea, the Sea of
      Japan (plus Okinawa) and the South China Sea, respectively, mostly in agreement
      with our previous mtDNA analysis. With the tropical South China Sea inferred as
      the origin, the East China Sea-Yellow Sea and the Sea of Japan clades in the
      north diverged successively from the ancestral clade during the mid-Pleistocene.
      The divergence of the three clades likely resulted from isolation of the three
      marginal seas caused by sea level change in the Pleistocene. Two sympatric zones,
      one of the East China Sea-Yellow Sea and the South China Sea clades in southeast
      China and the other of the East China Sea-Yellow Sea and the Sea of Japan clades
      in Vladivostok, are demonstrated to be hybrid zones, with hybridization occurring
      currently in the former but historically in the latter. Adaptive speciation is
      observed in the divergence process of the three clades, possibly because of
      selection from accumulated temperature. Our study indicates that the genetic
      structure and evolutionary history of Eriocheir s. s. have been primarily
      affected by Pleistocene glacial cycles, secondarily by divergent selection and
      drainage isolation, but only minimally by human activities.

PMID- 22465486
TI  - Positive associations between respiratory outcomes and fungal index in rural
      inhabitants of a representative sample of French dwellings.
AB  - Our study aims at estimating exposure to molds at home, based on microbial
      Volatile Organic Compounds (MVOCs) assessment, and evaluating its effect on
      respiratory diseases in a representative sample of dwellings. In the framework of
      a national campaign, indoor pollution was monitored in a sample of the 24 million
      dwellings of metropolitan France (n=567). 727 subjects answered to a standardized
      questionnaire on respiratory diseases and had MVOCs sampled in their bedrooms and
      a fungal index (FI) defined. Among the 431 dwellings with complete data, one out
      of three was contaminated by molds as assessed by a positive FI: 27.0% in urban,
      38.2% in periurban and 34.9% in rural dwellings respectively. Positive
      associations were observed between fungal index and current asthma (8.6%) and
      chronic bronchitis-like symptoms (8.4%), especially in rural areas (OR=2.95,
      95%CI (1.10; 7.95) and 3.35, 95%CI (1.33; 8.48) respectively). Our study, based
      on objective assessments of fungal contamination, is in agreement with previous
      results suggesting mold-related respiratory effects. Moreover associations found
      among rural population could indicate specific pollution and impact in this
      environment.

PMID- 22465487
TI  - Biomimetic hydrogels for controlled biomolecule delivery to augment bone
      regeneration.
AB  - The regeneration of large bone defects caused by trauma or disease remains a
      significant clinical problem. Although osteoinductive growth factors such as bone
      morphogenetic proteins have entered clinics, transplantation of autologous bone
      remains the gold standard to treat bone defects. The effective treatment of bone
      defects by protein therapeutics in humans requires quantities that exceed the
      physiological doses by several orders of magnitude. This not only results in very
      high treatment costs but also bears considerable risks for adverse side effects.
      These issues have motivated the development of biomaterials technologies allowing
      to better control biomolecule delivery from the solid phase. Here we review
      recent approaches to immobilize biomolecules by affinity binding or by covalent
      grafting to biomaterial matrices. We focus on biomaterials concepts that are
      inspired by extracellular matrix (ECM) biology and in particular the dynamic
      interaction of growth factors with the ECM. We highlight the value of synthetic,
      ECM-mimicking matrices for future technologies to study bone biology and develop
      the next generation of 'smart' implants.

PMID- 22465488
TI  - Naturally and synthetic smart composite biomaterials for tissue regeneration.
AB  - The development of smart biomaterials for tissue regeneration has become the
      focus of intense research interest. More opportunities are available by the
      composite approach of combining the biomaterials in the form of biopolymers
      and/or bioceramics either synthetic or natural. Strategies to provide smart
      capabilities to the composite biomaterials primarily seek to achieve matrices
      that are instructive/inductive to cells, or that stimulate/trigger target cell
      responses that are crucial in the tissue regeneration processes. Here, we review
      in-depth, recent developments concerning smart composite biomaterials available
      for delivery systems of biofactors and cells and scaffolding matrices in tissue
      engineering. Smart composite designs are possible by modulating the bulk and
      surface properties that mimic the native tissues, either in chemical
      (extracellular matrix molecules) or in physical properties (e.g. stiffness), or
      by introducing external therapeutic molecules (drugs, proteins and genes) within
      the structure in a way that allows sustainable and controllable delivery, even
      time-dependent and sequential delivery of multiple biofactors. Responsiveness to
      internal or external stimuli, including pH, temperature, ionic strength, and
      magnetism, is another promising means to improve the multifunctionality in smart
      scaffolds with on-demand delivery potential. These approaches will provide the
      next-generation platforms for designing three-dimensional matrices and delivery
      systems for tissue regenerative applications.

PMID- 22465489
TI  - Phosphorus: a limiting nutrient for humanity?
AB  - Phosphorus is a chemical element that is essential to life because of its role in
      numerous key molecules, including DNA and RNA; indeed, organisms require large
      amounts of P to grow rapidly. However, the supply of P from the environment is
      often limiting to production, including to crops. Thus, large amounts of P are
      mined annually to produce fertilizer that is applied in support of the 'Green
      Revolution.' However, much of this fertilizer eventually ends up in rivers, lakes
      and oceans where it causes costly eutrophication. Furthermore, given increasing
      human population, expanding meat consumption, and proliferating bioenergy
      pressures, concerns have recently been raised about the long-term geological,
      economic, and geopolitical viability of mined P for fertilizer production.
      Together, these issues highlight the non-sustainable nature of current human P
      use. To achieve P sustainability, farms need to become more efficient in how they
      use P while society as a whole must develop technologies and practices to recycle
      P from the food chain. Such large-scale changes will probably require a radical
      restructuring of the entire food system, highlighting the need for prompt but
      sustained action.

PMID- 22465490
TI  - Novel transcripts in the maxillary venom glands of advanced snakes.
AB  - Venom proteins are added to reptile venoms through duplication of a body protein
      gene, with the duplicate tissue-specifically expressed in the venom gland.
      Molecular scaffolds are recruited from a wide range of tissues and with a similar
      level of diversity of ancestral activity. Transcriptome studies have proven an
      effective and efficient tool for the discovery of novel toxin scaffolds. In this
      study, we applied venom gland transcriptomics to a wide taxonomical diversity of
      advanced snakes and recovered transcripts encoding three novel protein scaffold
      types lacking sequence homology to any previously characterised snake toxin type:
      lipocalin, phospholipase A2 (type IIE) and vitelline membrane outer layer
      protein. In addition, the first snake maxillary venom gland isoforms were
      sequenced of ribonuclease, which was only recently sequenced from lizard
      mandibular venom glands. Further, novel isoforms were also recovered for the only
      recently characterised veficolin toxin class also shared between lizard and snake
      venoms. The additional complexity of snake venoms has important implications not
      only for understanding their molecular evolution, but also reinforces the
      tremendous importance of venoms as a diverse bio-resource.

PMID- 22465491
TI  - Local inflammatory events induced by Bothrops atrox snake venom and the release
      of distinct classes of inflammatory mediators.
AB  - Bothrops atrox is responsible for most accidents involving snakes in the
      Brazilian Amazon and its venom induces serious systemic and local effects. The
      local effects are not neutralized effectively by commercial antivenoms, resulting
      in serious sequelae in individuals bitten by this species. This study
      investigates the local inflammatory events induced in mice by B. atrox venom
      (BaV), such as vascular permeability, leukocyte influx and the release of
      important inflammatory mediators such as cytokines, eicosanoids and the chemokine
      CCL-2, at the injection site. The effect of BaV on cyclooxygenase (COX-1 and COX
      2) expression was also investigated. The results showed that intraperitoneal
      (i.p.) injection of BaV promoted a rapid and significant increase in vascular
      permeability, which reached a peak 1 h after venom administration. Furthermore,
      BaV caused leukocyte infiltration into the peritoneal cavity between 1 and 8 h
      after i.p. injection, with mononuclear leukocytes (MNs) predominating in the
      first 4 h, and polymorphonuclear leukocytes (PMNs) in the last 4 h. Increased
      protein expression of COX-2, but not of COX-1, was detected in leukocytes
      recruited in the first and fourth hours after injection of BaV. The venom caused
      the release of eicosanoids PGD2, PGE2, TXA2 and LTB4, cytokines TNF-alpha, IL-6,
      IL-10 and IL-12p70, but not IFN-gamma, and chemokine CCL-2 at different times.
      The results show that BaV is able to induce an early increase in vascular
      permeability and a leukocyte influx to the injection site consisting mainly of
      MNs initially and PMNs during the later stages. These phenomena are associated
      with the production of cytokines, the chemokine CCL-2 and eicosanoids derived
      from COX-1 and COX-2.

PMID- 22465492
TI  - Cutaneous loxoscelism caused by Loxosceles similis venom and neutralization
      capacity of its specific antivenom.
AB  - Members of the spider genus Loxosceles pose a marked health risk to humans
      because of the seriousness of the necrotic and systemic effects of their bite,
      known as loxoscelism. The recent confirmation of Loxosceles similis in residences
      of Belo Horizonte in Minas Gerais Province, Brazil increases the local potential
      risk of loxoscelism at higher levels. The first characterization of the venom
      from this species showed that its main biological effects had a similar intensity
      as other species (e.g. Loxosceles intermedia, Loxosceles laeta, and Loxosceles
      gaucho). Therefore, we wished to further analyse the biological activity of the
      L. similis venom as well as the capacity of anti-L. similis-venom serum to reduce
      dermonecrotic effects to rabbit skin. Histological analysis of rabbit skin 2, 4
      and 8h after intradermal injection of L. similis venom demonstrated a dense
      inflammatory infiltrate, edema, degeneration and necrosis of the skin muscle,
      dissociation of collagen fibers, and disruption of reticular fibers. Importantly,
      pre-incubation of the venom with anti-L. similis-venom serum significantly
      decreased all of these effects. Anti-L. similis antivenom generated antibodies
      that were strongly reactive to L. similis venom and capable of neutralizing the
      dermonecrotic effects in rabbits caused by this venom. Moreover, the antivenom
      significantly reduced the sphingomyelinase activity of L. similis crude venom.
      Venoms produced by male and female spiders were equally reactive towards anti-L.
      similis and anti-L. intermedia antivenoms, but female venom induced larger
      lesions on rabbits. In contrast, female venom acted as an immunization enhancer
      and protected animals from L. similis envenomation to a greater degree than male
      venom. In conclusion, the results shown in this study for L. similis antivenom
      merits a more in depth study of its properties, which may become a valuable tool
      against loxoscelism.

PMID- 22465493
TI  - Management of snakebites in France.
AB  - Although not a major health problem in Europe, snakebite in the old continent was
      the focus of recent studies to evaluate their overall incidence and define
      management techniques. The purpose of this three-part report is to present the
      experience of the Marseille Poison Centre with snakebite in France. The first
      section deals with viper envenomation that now benefits from a validated
      therapeutic protocol using of purified antivenom of proven efficacy and tolerance
      in patients showing grade 2 and 3 symptoms. The second section describes the
      highly variable snakebite situation in French overseas territories that include
      areas where local species require specialized management, e.g. Martinique and
      French Guiana. The third section involves the emerging problems associated with
      the keeping of exotic snakes as pets with problems related to the use of
      antivenoms from foreign countries. The exotic-snake pets fashion was at the
      origin of the creation of a national antivenom bank by two French poison centers
      (Angers and Marseille) to ensure prompt delivery of antivenoms for exotic snake
      envenomation anywhere in mainland France.

PMID- 22465494
TI  - Seasonality of brown recluse populations is reflected by numbers of brown recluse
      envenomations.
AB  - A significant seasonal correlation was recently shown for brown recluse spider
      activity. Vetter (2011) observed brown recluse spiders were submitted by the
      general public predominantly during April-October. For patients with suspected
      brown recluse spider bites (BRSB), we have observed the same seasonality. Among
      45 cases with features consistent of a BRSB, 43 (95.6%) occurred during April
      October. Both the Vetter study and our study serve to demonstrate seasonal
      activity for brown recluse spiders.

PMID- 22465496
TI  - Yeast as a model eukaryote in toxinology: a functional genomics approach to
      studying the molecular basis of action of pharmacologically active molecules.
AB  - Yeast Saccharomyces cerevisiae has proven to be a relevant and convenient model
      organism for the study of diverse biological phenomena, due to its
      straightforward genetics, cost-effectiveness and rapid growth, combined with the
      typical characteristics of a eukaryotic cell. More than 40% of yeast proteins
      share at least part of their primary amino acid sequence with the corresponding
      human protein, making yeast a valuable model in biomedical research. In the last
      decade, high-throughput and genome-wide experimental approaches developed in
      yeast have paved the way to functional genomics that aims at a global
      understanding of the relationship between genotype and phenotype. In this review
      we first present the yeast strain and plasmid collections for genome-wide
      experimental approaches to study complex interactions between genes, proteins and
      endo- or exogenous small molecules. We describe methods for protein-protein,
      protein-DNA, genetic and chemo-genetic interactions, as well as localization
      studies, focussing on their application in research on small pharmacologically
      active molecules. Next we review the use of yeast as a model organism in
      neurobiology, emphasizing work done towards elucidating the pathogenesis of
      neurodegenerative diseases and the mechanism of action of neurotoxic
      phospholipases A(2).

PMID- 22465495
TI  - Anti-invasive and anti-adhesive activities of a recombinant disintegrin, r
      viridistatin 2, derived from the Prairie rattlesnake (Crotalus viridis viridis).
AB  - Snake venom disintegrins inhibit platelet aggregation and have anti-cancer
      activities. In this study, we report the cloning, expression, and functional
      activities of a recombinant disintegrin, r-viridistatin 2 (GenBank ID: JQ071899),
      from the Prairie rattlesnake. r-Viridistatin 2 was tested for anti-invasive and
      anti-adhesive activities against six different cancer cell lines (human urinary
      bladder carcinoma (T24), human fibrosarcoma (HT-1080), human skin melanoma (SK
      Mel-28), human colorectal adenocarcinoma (CaCo-2), human breast adenocarcinoma
      (MDA-MB-231) and murine skin melanoma (B16F10)). r-Viridistatin 2 shares 96% and
      64% amino acid identity with two other Prairie rattlesnake medium-sized
      disintegrins, viridin and viridistatin, respectively. r-Viridistatin 2 was able
      to inhibit adhesion of T24, SK-MEL-28, HT-1080, CaCo-2 and MDA-MB-231 to various
      extracellular matrix proteins with different affinities. r-Viridistatin 2
      decreased the ability of T24 and SK-MEL-28 cells to migrate by 62 and 96%
      respectively, after 24 h of incubation and the invasion of T24, SK-MEL-28, HT
      1080 and MDA-MB-231 cells were inhibited by 80, 85, 65 and 64% respectively,
      through a reconstituted basement membrane using a modified Boyden chamber.
      Finally, r-viridistatin 2 effectively inhibited lung colonization of murine
      melanoma cells in BALB/c mice by 71%, suggesting that r-viridistatin 2 could be a
      potent anti-cancer agent in vivo.

PMID- 22465497
TI  - Dendrimers reduce toxicity of Abeta 1-28 peptide during aggregation and
      accelerate fibril formation.
AB  - The influence of a GATG (gallic acid-triethylene glycol) dendrimer decorated with
      27 terminal morpholine groups ([G3]-Mor) on the aggregation process of
      Alzheimer's peptide has been investigated. Amyloid fibrils were formed from the
      Abeta 1-28 peptide and the process was monitored by a ThT assay, changes in CD
      spectra, and transmission electron microscopy. In the presence of [G3]-Mor, more
      fibrils were built and the process significantly accelerated compared with a
      control. The cytotoxicity of (1) Abeta and (2) the system [G3]-Mor/Abeta was
      monitored at different stages of the aggregation process. Prefibrillar species
      were more toxic than mature fibrils. [G3]-Mor significantly reduced the toxicity
      of Abeta, probably because of lowering the amount of prefibrillar forms in the
      system by speeding up the process of fibril formation. FROM THE CLINICAL EDITOR:
      In this study, GATG dendrimer decorated with 27 terminal morpholine groups was
      able to reduce beta-amyloid fibril formation, which might represent a new method
      to address the key pathology in Alzheimer's disease.

PMID- 22465498
TI  - Nanoliposomal minocycline for ocular drug delivery.
AB  - Nanoliposomal technology is a promising drug delivery system that could be
      employed to improve the pharmacokinetic properties of clearance and distribution
      in ocular drug delivery to the retina. We developed a nanoscale version of an
      anionic, cholesterol-fusing liposome that can encapsulate therapeutic levels of
      minocycline capable of drug delivery. We demonstrate that size extrusion followed
      by size-exclusion chromatography can form a stable 80-nm liposome that
      encapsulates minocycline at a concentration of 450 +/- 30 MUM, which is 2% to 3%
      of loading material. More importantly, these nontoxic nanoliposomes can then
      deliver 40% of encapsulated minocycline to the retina after a subconjunctival
      injection in the STZ model of diabetes. Efficacy of therapeutic drug delivery was
      assessed via transcriptomic and proteomic biomarker panels. For both the free
      minocycline and encapsulated minocycline treatments, proinflammatory markers of
      diabetes were downregulated at both the messenger RNA and protein levels,
      validating the utility of biomarker panels for the assessment of ocular drug
      delivery vehicles. FROM THE CLINICAL EDITOR: Authors developed a nano-liposome
      that can encapsulate minocycline for optimized intraocular drug delivery. These
      nontoxic nanoliposomes delivered 40% of encapsulated minocycline to the retina
      after a subconjunctival injection in a diabetes model.

PMID- 22465499
TI  - VSG 117 gene is conservatively present and early expressed in Trypanosma evansi
      YNB stock.
AB  - African trypanosomes, including Trypanosoma brucei and the closely related
      species Trypanosoma evansi, are flagellated unicellular parasites that
      proliferate extracellularly in the mammalian bloodstream and tissue spaces. They
      evade host immune system by periodically switching their variant surface
      glycoprotein (VSG) coat. Each trypanosome possesses a vast archive of VSGs with
      distinct sequence identity and different strains contain different archive of
      VSGs. VSG 117 was reported as a widespread VSG detected in the genomes of all the
      T. brucei strains. In this study, the presence and expression of VSG 117 gene was
      observed in T. evansi YNB stock by RT-PCR with VSG-specific primers. We further
      confirmed that this VSG tends to be expressed in the early stage of T. evansi
      infections (on day 12-15) by immuno-screening the previously isolated infected
      blood samples. It is possible that the VSG 117 gene evolved and spread through
      the African trypanosome population via genetic exchange, before T. evansi lost
      its ability to infect tsetse fly. Our finding provided an evidence of the close
      evolutionary relationship between T. evansi and T. brucei, in the terms of VSG
      genes.

PMID- 22465500
TI  - A high prevalence of Theileria penicillata in woylies (Bettongia penicillata).
AB  - The woylie or brush-tailed bettong (Bettongia penicillata) is a medium-sized
      native Australian marsupial that has undergone a dramatic decline in numbers in
      recent years. Trypanosome parasites have been identified in the woylie but little
      is known about the prevalence and clinical impact of other haemoprotozoan
      parasites in these marsupials. In the present study, the occurrence and molecular
      phylogeny of a piroplasm was studied in woylies from six different sites in
      Western Australia (WA). Blood samples were screened by PCR at the 18S rRNA locus
      and 80.4% (123/153) of the blood samples were positive for piroplasm DNA.
      Sequence and phylogenetic analysis of 12 of these positives identified them as
      Theileria penicillata, and sequencing of cloned PCR products indicated that no
      other species of Theileria were present. Infected woylies had a lower body weight
      but microscopic evaluation of the blood films indicated that T. penicillata did
      not appear to cause red cell injury or anaemia. Further studies are required to
      determine the clinical significance of T. penicillata in woylies.

PMID- 22465501
TI  - Fatty acids oxidation and alternative energy sources detected in Taenia
      crassiceps cysticerci after host treatment with antihelminthic drugs.
AB  - Human cysticercosis caused by Taenia crassiceps is rare however it is considered
      of zoonotic risk. The treatment of the infected patients was successful when
      using albendazole or praziquantel. The active forms of albendazole inhibit the
      glucose uptake and the active forms of praziquantel alter glycogen levels and
      nutrients absorption. The aim of this study was to analyze the production of
      organic acids that indicate the oxidation of fatty acids and the use of
      alternative energy sources from T. crassiceps cysticerci removed from the
      peritoneal cavity of mice treated with low dosages of albendazole (5.75 and
      11.5mg/kg) or praziquantel (3.83 and 7.67 mg/kg). The beta-hydroxibutyrate
      production was higher by the larval stage cysticerci in all treated groups and
      the propionate production was higher in final stage cysticerci treated with
      11.5mg/kg of albendazole when compared to the control group. The larval stages of
      cysticerci from the groups treated with 5.75 mg/kg of albendazole and 3.83 mg/kg
      of praziquantel produced more urea than the initial and final stages which
      indicate amino acids breakdown. We conclude that it was possible to detect the
      fatty acid oxidation and amino acids breakdown which indicate the use of
      alternative energy production sources as the used dosages only cause a partial
      blockage of the glucose uptake and leads to metabolic alterations in the
      cysticerci. The metabolic behavior observed after host treatment was different
      from former descriptions of the in vitro one which indicates great host-parasite
      interaction.

PMID- 22465502
TI  - Mechanism-based CYP2D6 inactivation by acridone alkaloids of Indonesian medicinal
      plant Lunasia amara.
AB  - Fourteen acridone alkaloids isolated from Lunasia amara Blanco were tested for
      their mechanism-based inhibition on human liver microsomal dextromethorphan O
      demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6).
      Among the 14 compounds, 5-hydroxygraveroline (1), 8-methoxyifflaiamine (2),
      lunamarine (3), and lunine (12) increased their inhibitory activity with
      increasing preincubation time. Then, we further examined the possibility of
      mechanism-based inhibition on 5-hydroxygraveroline (1) and lunamarine (3), which
      showed the potent inhibition. Further investigations on 1 and 3 showed that the
      characteristic time- and concentration-dependent inhibition, which required a
      catalytic step with NADPH, was not protected by nucleophiles, and was decreased
      by the presence of a competitive inhibitor. Thus, 1 and 3 were concluded as
      mechanism-based inactivators of CYP2D6.

PMID- 22465503
TI  - Cytotoxic triterpene saponins from the leaves of Aralia elata.
AB  - Phytochemical investigation of the leaves of Aralia elata has led to the
      isolation of four new compounds, 3-O-beta-D-glucopyranosyl (1->3)-beta-D
      glucopyranosyl (1->3)-beta-D-glucopyranosyl oleanolic acid (1), 3-O-[beta-D
      glucopyranosyl (1->3)-beta-D-glucopyranosyl (1->3)]-[beta-D-glucopyranosyl (1
      >2)]-beta-d-glucopyranosyl hederagenin 28-O-beta-D-glucopyranoside (2), 3-O
      {[beta-D-glucopyranosyl (1->2)]-[beta-d-glucopyranosyl (1->3)-beta-d
      glucopyranosyl (1->3)]-beta-D-glucopyranosyl} oleanolic acid 28-O-beta-D
      glucopyranosyl ester (3) and 3-O-[beta-D-glucopyranosyl (1->2)]-[beta-D
      glucopyranosyl (1->3)]-beta-d-glucopyranosyl caulophyllogenin (4) and two known
      compounds, 3-O-[beta-D-glucopyranosyl (1->3)-alpha-l-arabinopyranosyl]
      echinocystic acid (5) and 3-O-alpha-L-arabinopyranosyl echinocystic acid (6). The
      structural determination was accomplished with spectroscopic analysis, in
      particular (13)C-NMR, 2D-NMR and HR-ESI-MS techniques. Compounds 1-6 were tested
      for their inhibition of the growth of HL60, A549 and DU145 cancer cells. Compound
      1 showed significant cytotoxic activity against HL60 and A549 cancer cells with
      IC(50) values of 6.99MUM and 7.93MUM respectively. In addition, compounds 5 and 6
      showed significant cytotoxic activity against HL60 cancer cells with IC(50)
      values of 5.75MUM and 7.51MUM, respectively.

PMID- 22465504
TI  - Anti-inflammatory and analgesic potential of a novel steroidal derivative from
      Bryophyllum pinnatum.
AB  - A new steroidal derivative, urs Stigmast-4, 20 (21), 23-trien-3-one and other
      four compounds were isolated from the leaves of Bryophyllum pinnatum. The
      structure of this new steroid was elucidated and established by standard
      spectroscopic methods. Carrageenan induced paw edema model was used for anti
      inflammatory and acetic acid induced model used for analgesic activity. This new
      steroidal compound was found to be active in reducing inflammation (% inhibition
      87.29 and 84.45 respectively) when compared with diclofenac. Further, it showed
      75.72% protection in analgesic activity in acetic acid induced writhing test in
      mice. In conclusion the % inhibition against carrageenan induced rat paw edema
      and % protection against acetic acid induced writhings showed by new compound
      revealed that the anti-inflammatory and analgesic activity of aqueous extract B.
      pinnatum are mainly due to the presence of this steroidal compound.

PMID- 22465505
TI  - Four new sesquiterpenes from Commiphora myrrha and their neuroprotective effects.
AB  - Four new sesquiterpenes, myrrhterpenoids K-N (1-4) have been isolated from the
      resin of Commiphora myrrha. Their structures and relative configurations were
      elucidated by spectroscopic methods (IR, ESIMS, HR-ESIMS, 1D and 2D NMR).
      Compounds 1 and 4 showed neuroprotective effects against MPP(+)-induced neuronal
      cell death in SH-SY5Y cells.

PMID- 22465506
TI  - Anti-Helicobacter pylori activity of Terminalia macroptera root.
AB  - The root of Terminalia macroptera Guill. & Perr. (Combretaceae) is widely used in
      African traditional medicine to treat various infectious diseases, including
      stomach-associated diseases. This study investigates the in vitro activity of T.
      macroptera root extract against reference strains and clinical isolates of H.
      pylori and attempts to localize the extract bioactivity. T. macroptera
      hydroethanol (80% V/V) root extract (Tmr) activity was tested against three
      standard strains and sixty two clinical strains of H. pylori. Tmr liquid-liquid
      partition fractions were screened against twenty H. pylori strains. Qualitative
      analysis of Tmr and its fractions was performed by HPLC-UV/DAD. The antibiotic
      characterization of the H. pylori strains revealed that 20% of the tested
      clinical isolates were resistant to at least two of the three antibiotics
      belonging to the main groups of antibiotics used in multi-therapy to eradicate H.
      pylori infections. In contrast, Tmr showed anti-H. pylori activity against the
      majority (92%) of the tested strains (MIC(50) and MIC(90)=200 MUg/ml). The Tmr
      water liquid-liquid fraction (Tmr-3) and the precipitate obtained from this
      fraction (Tmr-5) were the most active tested samples, showing a MIC(50) of 100
      MUg/ml. The present work proves the in vitro activity of T. macroptera against H.
      pylori, thus confirming the utility of this traditional medicinal plant to treat
      stomach complaints due to H. pylori infection. The main compounds of Tmr and of
      Tmr-3 were the ellagitannins terchebulin and punicalagin. These compounds can be
      considered as markers of T. macroptera root active extracts against H. pylori.

PMID- 22465507
TI  - Pharmacokinetics and tissue distribution study of scoparone in rats by
      ultraperformance liquid-chromatography with tandem high-definition mass
      spectrometry.
AB  - Scoparone is an important constituent of Yinchenhao (Artemisia annua L.), a
      famous Chinese medicinal plant, and has several known bioactivities, and
      displayed bright prospects in prevention and therapy of jaundice and liver
      disorders. The aim of this study was to investigate the in vivo plasma
      pharmacokinetic and tissue distribution characteristics of scoparone after oral
      administration. The levels of scoparone in plasma, and tissues were measured by a
      rapid and sensitive UPLC-MS/MS method. The biosamples were prepared using
      methanolic precipitation and the separation of scoparone was achieved on a UPLC
      HSS T3 column by linear gradient elution using water (containing 0.1% formicacid)
      and acetonitrile (containing 0.1% formic acid) as the mobile phase at a flow rate
      of 0.5mL/min The total run time was only 3.9min. Our results successfully
      demonstrate that this method has excellent and satisfactory selectivity,
      sensitivity, linearity, precision, accuracy and recovery. The estimated
      pharmacokinetic parameters (i.e., C(max), AUC and CL), were C(max)=14.67mg/L,
      AUC=81.15mg*h/L, CL=1.23L/h for scoparone. The pharmacokinetic study found that
      scoparone was distributed and eliminated rapidly in rats. Tissue distribution
      showed the highest level was observed in liver, followed by the kidney and
      spleen; the lower level appeared in the muscle, thyroid, and adrenal. It was not
      detected in the brain which indicated that scoparone does not cross the blood
      brain barrier after oral administration. Our developed method was suitable for
      the study on pharmacokinetics and tissue distribution of scoparone after oral
      administration.

PMID- 22465508
TI  - Anti-androgenic effect of sesquiterpenes isolated from the rhizomes of Curcuma
      aeruginosa Roxb.
AB  - Six sesquiterpenes: germacrone (1), zederone (2), dehydrocurdione (3), curcumenol
      (4), zedoarondiol (5) and isocurcumenol (6) were isolated from rhizomes of
      Curcuma aeruginosa Roxb. (Zingiberaceae). They inhibited 5alpha-reductase which
      converts testosterone to dihydrotestosterone (DHT). Germacrone (1) was the most
      potent (IC(50)=0.42+/-0.05 mg/mL). Compound 1 was anti-androgenic in LNCaP cells
      when proliferation was testosterone-induced. The growth of flank gland of male
      Syrian hamsters is dependent on circulating androgen and when maintained with
      testosterone, 1 (3, 30, 100MUg) inhibited growth but was ineffective against DHT.
      The similar activity profile was observed on the 5alpha-reductase inhibitor,
      finasteride (100 MUg) treatment group. The androgen receptor binding assay showed
      that 1 did not bind to the androgen receptor. In conclusion, 1 showed anti
      androgenic effect on in vitro and in vivo assays. One of the possible mechanisms
      was inhibition 5alpha-reductase activity. Thus, 1 is a potential lead compound
      for treatment of androgen-dependent disorders.

PMID- 22465509
TI  - Effects of illumination and packaging on non-heme iron and color attributes of
      sliced ham.
AB  - This study was designed to investigate effects of illumination and packaging on
      color of cooked cured sliced ham during refrigeration, and the possibility of
      decomposition of nitrosylheme under light and oxygen exposure. Three illumination
      levels and three packaging films with different oxygen transmission rates (OTRs)
      were used in two separate experiments during 35 days storage, and pH value, a*
      value, nitrosylheme, residual nitrite and non-heme iron were evaluated. Packaging
      OTRs had significant effects (P<0.01) on a* value, but illumination level and
      packaging OTR did not affect (P>0.05) nitrosylheme concentration during storage.
      For both groups, storage time had a significant effect (P<0.01) on a* value and
      nitrosylheme. Negative relationships between nitrosylheme and nitrite in the
      illumination group, and between nitrosylheme and non-heme iron in the packaging
      group were observed. Therefore, illumination level and packaging OTR had limited
      effects on overall pigment stability, but more discoloration and loss of redness
      occurred on the surface of products.

PMID- 22465510
TI  - Polyphenolic content and antioxidant properties of Moringa oleifera leaf extracts
      and enzymatic activity of liver from goats supplemented with Moringa oleifera
      leaves/sunflower seed cake.
AB  - The study investigated antioxidant potency of Moringa oleifera leaves in
      different in vitro systems using standard phytochemical methods. The
      antioxidative effect on the activities of superoxide dismutase (SOD), catalase
      (CAT), lipid peroxidation (LPO) and reduced glutathione (GSH) were investigated
      in goats supplemented with M. oleifera (MOL) or sunflower seed cake (SC). The
      acetone extract had higher concentrations of total flavonoids (295.01 +/- 1.89
      QE/g) followed by flavonols (132.74 +/- 0.83 QE/g), phenolics (120.33 +/- 0.76
      TE/g) and then proanthocyanidins (32.59 +/- 0.50 CE/g) than the aqueous extract.
      The reducing power of both solvent extracts showed strong antioxidant activity in
      a concentration dependent manner. The acetone extract depicted higher percentage
      inhibition against DPPH, ABTS and nitric oxide radicals which were comparable
      with reference standard antioxidants (vitamin C and BHT). MOL increased the
      antioxidant activity of GSH (186%), SOD (97.8%) and catalase (0.177%). Lipid
      peroxidation was significantly reduced by MOL. The present study suggests that M.
      oleifera could be a potential source of compounds with strong antioxidant
      potential.

PMID- 22465512
TI  - Effects of Plantago major L. leaf extracts on oral epithelial cells in a scratch
      assay.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The present study was undertaken to evaluate the
      effects from different leaf extracts of the traditional medicinal herb Plantago
      major L. (plantain) on cell proliferation and migration in vitro, as a test for
      potential wound healing properties. MATERIALS AND METHODS: Water and ethanol
      based extracts were prepared from Plantago major fresh and dried leaves, and
      tested in vitro in a scratch assay with oral epithelial cells. RESULTS: The
      scratch assay produced reliable results after 18 h. Most of the tested extracts
      increased the proliferation/migration of the oral epithelial cells compared to
      the negative control. A concentration of 1.0 mg/mL (on dry weight basis) appears
      to be optimal regardless of type of extract, and among the alternatives, 0.1
      mg/mL was always better than 10 mg/mL. Ethanol-based extracts with a
      concentration of 10 mg/mL had very detrimental effects on cell
      proliferation/migration. At the other two concentrations, ethanol-based extracts
      had the most beneficial effect, followed by water extracts of fresh leaves,
      ethanol plus water extracts of dried leaves and, finally, water extracts of dried
      leaves. CONCLUSIONS: This study suggests that both the water extracts and the
      more polyphenol-rich ethanol-based extracts of Plantago major leaves have
      medicinal properties. Further research is, however, needed to determine what
      compounds are responsible for the wound healing effects.

PMID- 22465511
TI  - Refined views of multi-protein complexes in the erythrocyte membrane.
AB  - The erythrocyte membrane has been extensively studied, both as a model membrane
      system and to investigate its role in gas exchange and transport. Much is now
      known about the protein components of the membrane, how they are organised into
      large multi-protein complexes and how they interact with each other within these
      complexes. Many links between the membrane and the cytoskeleton have also been
      delineated and have been demonstrated to be crucial for maintaining the
      deformability and integrity of the erythrocyte. In this study we have refined
      previous, highly speculative molecular models of these complexes by including the
      available data pertaining to known protein-protein interactions. While the
      refined models remain highly speculative, they provide an evolving framework for
      visualisation of these important cellular structures at the atomic level.

PMID- 22465513
TI  - Characterization of rainbow trout gonad, brain and gill deep cDNA repertoires
      using a Roche 454-Titanium sequencing approach.
AB  - Rainbow trout, Oncorhynchus mykiss, is an important aquaculture species worldwide
      and, in addition to being of commercial interest, it is also a research model
      organism of considerable scientific importance. Because of the lack of a whole
      genome sequence in that species, transcriptomic analyses of this species have
      often been hindered. Using next-generation sequencing (NGS) technologies, we
      sought to fill these informational gaps. Here, using Roche 454-Titanium
      technology, we provide new tissue-specific cDNA repertoires from several rainbow
      trout tissues. Non-normalized cDNA libraries were constructed from testis, ovary,
      brain and gill rainbow trout tissue samples, and these different libraries were
      sequenced in 10 separate half-runs of 454-Titanium. Overall, we produced a total
      of 3million quality sequences with an average size of 328bp, representing more
      than 1Gb of expressed sequence information. These sequences have been combined
      with all publicly available rainbow trout sequences, resulting in a total of
      242,187 clusters of putative transcript groups and 22,373 singletons. To identify
      the predominantly expressed genes in different tissues of interest, we developed
      a Digital Differential Display (DDD) approach. This approach allowed us to
      characterize the genes that are predominantly expressed within each tissue of
      interest. Of these genes, some were already known to be tissue-specific, thereby
      validating our approach. Many others, however, were novel candidates,
      demonstrating the usefulness of our strategy and of such tissue-specific
      resources. This new sequence information, acquired using NGS 454-Titanium
      technology, deeply enriched our current knowledge of the expressed genes in
      rainbow trout through the identification of an increased number of tissue
      specific sequences. This identification allowed a precise cDNA tissue repertoire
      to be characterized in several important rainbow trout tissues. The rainbow trout
      contig browser can be accessed at the following publicly available web site
      (http://www.sigenae.org/).

PMID- 22465514
TI  - A case of primary selective hypoaldosteronism carrying three mutations in the
      aldosterone synthase (Cyp11b2) gene.
AB  - An infant with a clinical phenotype of early onset hypoaldosteronism has been
      screened for mutation analysis of the Cyp11b2 gene encoding aldosterone synthase
      enzyme. We have described a novel nonsense mutation in exon 3 (c.508C>T) that
      gave rise to a shorter protein (Q170X) and two known concurrent missense
      mutations (c.594A>C in exon 3 and c.1157T>C in exon 7) that led to substitution
      of glutamic acid for aspartic acid at amino acid position 198 (E198D) and of
      valine for alanine at amino acid position 386 (V386A). The father, who carried
      E198D plus V386A mutations, showed a fractional sodium excretion of 1.25% that
      was unmodified by dietary salt restriction, suggesting a mild haploinsufficiency.
      We examined by in silico analysis the effect of the mutations on the secondary
      and tertiary structures of aldosterone synthase to explain the inefficient
      enzymatic activity. The Q170X mutation produced a truncated protein, which was
      consequently associated with a loss of catalytic activity. As predicted by JPred
      web system and Dock 6.3 software, the concurrent expression of E198D and V386A
      mutations induced a significant secondary structure rearrangement and a shift of
      the heme group and the 18-hydroxycorticosterone substrate from their optimal
      placement.

PMID- 22465515
TI  - The use of bone morphogenic protein-7 (OP-1) in the management of resistant non
      unions in the upper and lower limb.
AB  - The aim of the present study was to investigate the safety and efficacy of local
      implantation of BMP-7 for the treatment of resistant non-unions in the upper and
      lower limb. Fifty-two patients (30 males, mean age 52.8 years; range 20-81) were
      treated with local BMP-7 implantation in a bovine bone-derived collagen paste
      with or without revision of fixation. Thirty-six patients had closed injuries,
      ten had open injuries and six had infected non-unions. Patients had undergone a
      mean of 2 (1-5) operations prior to implantation of BMP-7. Clinical and
      radiological union was achieved in 94% at a mean time of 5.6 months (3-19). Two
      patients with subtrochanteric femoral fractures failed to achieve union secondary
      to inadequate fracture stabilisation, persistent unfavourable biological
      environment and systemic co-morbidities. One patient developed synostosis
      attributed to the BMP-7 application. This study demonstrates BMP-7 implanted in a
      bovine-derived collagen paste is an effective adjunctive treatment for resistant
      non-unions in the upper and lower limb.

PMID- 22465516
TI  - Acute fractures to the proximal fifth metatarsal bone: development of
      classification and treatment recommendations based on the current evidence.
AB  - Fractures to the proximal fifth metatarsal bone are among the most frequent
      injuries to the foot. Various classifications intend to distinguish different
      fracture entities in regard to prognosis and treatment. The most commonly used
      classification by Lawrence and Botte delineates three fracture zones and gives
      treatment recommendations based on retrospective case series. Aim of our study
      was to critically review the literature and reevaluate the classification and
      treatment recommendations based on the highest level of evidence available. We
      performed a systematic literature search in Medline, Embase and Cochrane library
      and identified six prospective trials either comparing the same treatment for
      different fracture entities or different treatment strategies for the same
      fracture entity. The studies reveal that all "tuberosity avulsion fractures"
      (Zone 1, according to Lawrence and Botte) heal well using functional treatment.
      Even multifragmentary, displaced and intraarticular fractures in Zone 1 give
      comparable good results. Treatment with a short leg cast leads to a significant
      delay in return to preinjury level when compared to functional treatment. "Jones'
      fractures" (Zone 2) also demonstrate good to excellent results and complete bone
      healing when treated functionally. In contrast, "diaphyseal stress fractures"
      (Zone 3) at the distal limit of the fourth-fifth intermetatarsal articulation and
      just distally feature a significantly higher rate of treatment failure when
      treated non-operatively in a non-weight bearing short leg cast. Early
      intramedullary screw fixation leads to a significantly shorter time to bone
      healing and return to sport. In conclusion, acute fractures to the proximal fifth
      metatarsal bone should be classified into two entities only: First, metaphyseal
      fractures not extending beyond the distal end of the fourth-fifth intermetatarsal
      articulation, as these fractures, regardless the number of fragments,
      displacement and intraarticular involvement, should be treated functionally.
      Second, meta-diaphyseal fractures located at the distal end of the fourth-fifth
      intermetatarsal articulation or just distally, as these fractures require early
      intramedullary screw fixation.

PMID- 22465517
TI  - Orthopaedic injuries associated with hip fractures in those aged over 60 years: a
      study of patterns of injury and outcomes for 1971 patients.
AB  - INTRODUCTION: There has been little research into the consequence of suffering a
      hip fracture and associated orthopaedic injures. The aim of this research paper
      is to describe the patient characteristics, patterns of injury and to define the
      effect on outcomes of orthopaedic injuries occurring simultaneously with hip
      fractures. PATIENTS AND METHODS: Hip fracture data was collected prospectively.
      Patients under 60 years of age were excluded from the study. Between 2004 and
      2010 we treated 1971 consecutive patients aged 60 years or older with a hip
      fracture. RESULTS: 81 (4.1%) patients sustained a simultaneous fracture or
      dislocation. 90% (73/81) of these injuries were in the upper limb and 88% (71/81)
      were ipsilateral, with the wrist (34 cases) and the proximal humerus (21 cases)
      being the commonest site of injury. Median hospital stay was significantly longer
      for those with additional injures. Pubic rami fractures were not seen in
      association with a hip fracture. Those patients who sustained a concomitant wrist
      fracture tended to be slightly fitter than those without associated injuries
      whist those with an associated humeral fracture were slightly frailer. Mortality
      was increased for those with an associated proximal humeral fracture but was
      lower with an associated wrist fracture. DISCUSSION AND CONCLUSION: Simultaneous
      injuries occurring with hip fractures are mainly seen in the ipsilateral upper
      limb. They present a greater challenge to the multidisciplinary team than a
      solitary hip fracture, experiencing a longer hospital stay and inevitably a
      higher financial cost. Those patients with wrist fractures have the best
      prognosis in terms of mortality, whereas a proximal humerus fracture may indicate
      a higher risk of mortality.

PMID- 22465518
TI  - Immunohistochemical investigation of lymphatic vessel formation control in mouse
      tooth development: lymphatic vessel-forming factors and receptors in tooth
      development in mice.
AB  - The presence of lymphatic vessels in dental pulp has recently been controversial,
      and no conclusion has been reached. In this study, we investigated the control of
      lymphangiogenesis with dental pulp development in the mouse mandibular molar
      using VEGF-C, VEGF-D, and VEGFR-3 as indices of lymphatic vessel-controlling
      factors. In addition, to distinguish blood and lymphatic vascular epithelial
      cells, we performed immunohistochemical analysis using von Willebrand factor
      (vWF) and statistical analysis. In dental papilla in the bell-stage non-calcified
      period, mesenchymal cells positive for VEGF-C, VEGF-D, and VEGFR-3 increased and
      lumen-forming endothelial cells were noted, but vWF was negative, suggesting that
      these were actively forming lymphatic vessels. Positive undifferentiated
      mesenchymal cells, an increase in endothelial cells in dental pulp, and lumen
      expansion were noted early after birth. Positivity was also detected in the
      odontoblast layer and sheath of Hertwig after birth, suggesting that these
      factors also play important roles in odontoblast differentiation and maturation
      and periodontal ligament and tooth root formation. We embryologically clarified
      lymphatic vessel formation in dental pulp and a process of lymphatic vessel
      formation from blood vessels, suggesting involvement of the surrounding tissue,
      odontoblasts, and sheath of Hertwig in vessel formation.

PMID- 22465519
TI  - Characterization of the 10q26-orthologue in rhesus monkeys corroborates a
      functional connection between ARMS2 and HTRA1.
AB  - Age-related macular degeneration, which is the leading cause of blindness in
      industrialized countries, is a multifactorial, degenerative disorder of the
      macula with strong heritability. For age-related macular degeneration in humans,
      the genes ARMS2 and HTRA1 in the region 10q26 are both promising candidates for
      being involved in pathogenesis. However, the associated variants are located in a
      region of strong linkage disequilibrium and so far, the identification of the
      causative gene in humans was not yet possible. This dilemma might be solved using
      an appropriate model organism. Rhesus monkeys suffer from drusen, a major
      hallmark of age-related macular degeneration, and the drusen-phenotype shares
      susceptibility factors with human macular degeneration. Thus, the rhesus monkey
      represents a natural animal model to uncover genetic factors leading to macular
      degeneration. Moreover, the existence of genetically homogenous cohorts offers an
      excellent opportunity to determine risk factors. However, the 10q26-orthologue
      genomic region in rhesus monkeys is not characterized in detail so far.
      Therefore, the aim of this study is to analyze the rhesus linkage disequilibrium
      structure and to investigate whether variants in ARMS2 or HTRA1 are associated
      with the drusen-phenotype as well. We sequenced parts of a 20 kb region around
      ARMS2 and HTRA1 in a genetically homogeneous cohort of 91 rhesus monkeys
      descending from the CPRC rhesus cohort on Cayo Santiago and currently housed in
      the German Primate Centre in Gottingen. Within this group, ophthalmoscopic
      examinations revealed a naturally high drusen prevalence of about 47% in monkeys
      >5 years. We detected 56 genetic variants within and around ARMS2 and HTRA1 and,
      as one deviates from Hardy-Weinberg-Equilibrium, 55 polymorphisms were used to
      generate a linkage disequilibrium-Plot and to perform association studies. We
      observed strong linkage disequilibrium between the markers and were able to
      define two haplotype blocks. One of these blocks spanned the whole ARMS2 locus
      and the 5' part of HTRA1 - almost perfectly resembling the situation found in
      humans. Tests for association revealed a variant in the promoter region of HTRA1
      and two variants in the 5'-UTR of ARMS2 to be associated with drusen. The strong
      linkage disequilibrium inhibits - as in humans - a determination of the risk gene
      using statistical methods only. However, the conserved linkage disequilibrium
      structure in humans and macaques goes in line with the recently emerged dual
      causality model proposing that ARMS2 and HTRA1 are functionally connected and
      that both genes contribute to the disease pathology. Moreover, the
      characterization of the 10q26-orthologue genomic region of the rhesus monkey
      provides a basis for now needed functional investigations in a well-characterized
      model organism.

PMID- 22465520
TI  - Ciona intestinalis notochord as a new model to investigate the cellular and
      molecular mechanisms of tubulogenesis.
AB  - Biological tubes are a prevalent structural design across living organisms. They
      provide essential functions during the development and adult life of an organism.
      Increasing progress has been made recently in delineating the cellular and
      molecular mechanisms underlying tubulogenesis. This review aims to introduce
      ascidian notochord morphogenesis as an interesting model system to study the cell
      biology of tube formation, to a wider cell and developmental biology community.
      We present fundamental morphological and cellular events involved in notochord
      morphogenesis, compare and contrast them with other more established
      tubulogenesis model systems, and point out some unique features, including
      bipolarity of the notochord cells, and using cell shape changes and cell
      rearrangement to connect lumens. We highlight some initial findings in the
      molecular mechanisms of notochord morphogenesis. Based on these findings, we
      present intriguing problems and put forth hypotheses that can be addressed in
      future studies.

PMID- 22465521
TI  - Small volume stage 1B1 cervical cancer: Is radical surgery still necessary?
AB  - OBJECTIVE: Current surgical treatment of FIGO stage 1B1 cervical cancer is
      radical surgery. However, several reports have shown that for small tumours a
      more conservative approach can be as effective in terms of survival, whilst at
      the same time reducing the morbidity associated with removing the parametrium.
      The objective of our study was to report survival and obstetric outcomes
      following conservative management of small-volume stage 1B1 disease. METHODS: All
      patients with FIGO stage 1B1 cancer and estimated tumour volume of less than 500
      mm(3) in a loop biopsy specimen were included in the study, irrespective of other
      histological characteristics. A second loop biopsy was performed to rule out
      residual disease in 79% of patients. RESULTS: Sixty two women were identified
      with a median age of 35 years (range 27-67). Median tumour length was 9.75 mm
      (7.2-20) and median depth of invasion was 1.55 mm (0.3-5). Thirty five women
      (56.4%) were treated with loop biopsy, whilst 27 (45.6%) had simple hysterectomy.
      Fifty seven women (92%) had pelvic lymphadenectomy and one positive node was
      recorded. After a median follow up of 56 months (16-132) no recurrence was noted.
      Seven full term pregnancies have been achieved. There were no preterm deliveries
      or mid-term miscarriages. CONCLUSION: Cervical loop biopsy or simple hysterectomy
      combined with negative pelvic lymphadenectomy for small-volume stage 1B1 cervical
      cancer offers excellent prognosis in terms of survival. Postoperative morbidity
      is reduced and obstetric outcomes may be improved. Should these results be
      verified by further prospective studies, radical surgery for these women may be
      avoided.

PMID- 22465522
TI  - Survivors of uterine cancer empowered by exercise and healthy diet (SUCCEED): a
      randomized controlled trial.
AB  - OBJECTIVE: The majority of endometrial cancer survivors (ECS) are obese and at
      risk for premature death. The purpose of this study was to evaluate an
      intervention for ECS to promote weight loss and a healthy lifestyle. METHODS:
      Early stage overweight and obese (body mass index >= 25) ECS (N=75) were
      randomized to a 6-month lifestyle intervention (LI) or usual care (UC). The LI
      group received education and counseling for six months (10 weekly followed by 6
      bi-weekly sessions). Weight change at 12 months was the primary endpoint.
      Secondary outcomes included fruit/vegetable servings/day and physical activity
      (PA). Multiple imputations were used for missing data and mixed models were used
      to analyze changes from baseline. RESULTS: Adherence was 84% and follow-up data
      were available from 92% of participants at 6 months and 79% at 12 months. Mean
      [95% CI] difference in weight change between LI and UC groups at 6 months was 
      4.4 kg [-5.3, -3.5], p<0.001 and at 12 months was -4.6 kg [-5.8, -3.5], p<0.001.
      Mean [95% CI] difference in PA minutes between groups at 6 months was 100 [6,
      194], p=0.038 and at 12 months was 89 [14, 163], p=0.020. Mean difference in
      kilocalories consumed was -217.8 (p<0.001) at 6 months and -187.2 (p<0.001) at 12
      months. Mean [95% CI] difference in fruit and vegetable servings was 0.91
      servings/day at 6 months and 0.92 at 12 months (p<0.001). CONCLUSIONS: Behavior
      change and weight loss are achievable in overweight and obese ECS, however, the
      clinical implications of these changes are unknown and require a larger trial
      with longer follow-up.

PMID- 22465523
TI  - Light-induced silencing of neural activity in Rosa26 knock-in mice conditionally
      expressing the microbial halorhodopsin eNpHR2.0.
AB  - Temporally precise inhibition of genetically defined cell populations in intact
      nervous systems has been enabled by the microbial halorhodopsin NpHR, a fast,
      light-activated chloride pump. Here, we report the generation of new mouse
      strains that express eNpHR2-EYFP fusion proteins after Cre- and/or Flp-mediated
      recombination to silence neural activity in vivo. In these mouse strains, Cre/Flp
      recombination induced a high-level of eNpHR2-EYFP expression. Slice whole-cell
      patch clamp experiments confirmed that eNpHR2-EYFP-expressing neurons could be
      optically hyperpolarized and inhibited from firing action potentials. Thus, these
      mouse strains offer powerful tools for light-induced silencing of neural activity
      in genetically defined cell populations.

PMID- 22465524
TI  - Principal Fourier component of motion stimulus dominates the initial optokinetic
      response in mice.
AB  - Optokinetic responses (OKRs) are reflexive eye movements elicited by a moving
      visual pattern, and have been recognized in a variety of species. Several
      brainstem and cortical structures are known to be implicated in the generation of
      OKRs in primates, while the OKRs of afoveate mammals have been posited to be
      dominated by subcortical structures. To understand the subcortical mechanism
      underlying OKRs, the initial OKRs to horizontal quarter-wavelength steps applied
      to vertical grating patterns were studied in adult C57BL/6J mice under the
      monocular viewing conditions. The initial OKRs to sinusoidal gratings showed
      directional asymmetry with temporal-to-nasal predominance, a common
      characteristic of afoveate mammals that uses the subcortical structures to elicit
      OKRs. We then examined whether the OKRs of afoveate mammals are driven by the
      same visual features of the moving images as those in primates. The OKRs in mice
      were elicited by using the missing fundamental (mf) stimuli and its variants that
      had been used to understand the mechanism(s) underlying the cortical control of
      eye movements in primates. We obtained the results indicating that the OKRs of
      mice are driven by the principal Fourier component of moving visual image as in
      primates despite the differences in neural circuitries.

PMID- 22465526
TI  - Breathing during cardiac arrest following exercise: a new function of the
      respiratory system?
AB  - We have found in four sheep that, following a muscular exercise, minute
      ventilation is maintained for 34-131 s during a cardiac arrest (CA), at a
      magnitude (from 28.2 and 54.7 l min(-1)) similar to the level of ventilation (and
      thus proportional to the metabolic rate) preceding the period of asystole.
      Breathing was maintained despite the lack of pulmonary blood flow and the
      cessation of the muscle contractions, leading to a dramatic reduction in alveolar
      FCO(2) (1.9 +/- 1%). Secondly, swings in arterial blood pressure (ABP) were
      observed (pulse pressure of 31 +/- 3 Torr) in phase with breathing movements in
      place of the cardiac activity. This "protective" response, deprived from any role
      in blood gas homeostasis, as circulation is virtually abolished, is not
      predictable from the traditional respiratory control feedback systems thought to
      be involved in exercise. We are presenting the view that this response,
      dissociated from the pulmonary gas exchanges, is the expression of a rudimentary
      defense mechanism aimed at limiting the consequences of an acute failure of the
      cardiac pump by the thoraco-abdominal pump.

PMID- 22465525
TI  - Workshop on personal motion technologies for healthy independent living:
      executive summary.
AB  - The objective of the June 2010 "Workshop on Personal Motions Technologies for
      Healthy Independent Living" was to discuss personal motion technologies that
      might enable older adults and individuals with disability to live independently
      for longer periods. The 60 participants included clinicians, academic
      researchers, engineers, patient advocates, caregivers, members of the public, and
      federal representatives. The workshop was divided into 6 sessions that addressed
      the following: (1) use of technologies in identifying early indicators of disease
      or adverse events; (2) monitoring daily activities; (3) coping with impairment;
      (4) managing mild cognitive impairment; (5) rehabilitation and exercise in the
      home; and (6) caregiver support. Presentations and discussion focused on clinical
      needs, the health impact of addressing those needs, state-of-the-art
      technologies, and challenges to adoption of those technologies. Conclusions
      included the following: (1) Involvement of end-users in research and development
      will increase the likelihood that technologies will be adopted. (2) Integration
      of differing types of technology into a system that includes clinical measures is
      required for independent living. (3) Seniors are willing to sacrifice some
      privacy for an effective technology that keeps them in their homes as long as
      they control who receives their data. (4) Multilevel and multiscale models are
      needed to understand motion in the context of the environment and to design
      effective systems.

PMID- 22465527
TI  - Urge-to-cough and dyspnea conceal perception of pain in healthy adults.
AB  - Although dyspnea has been shown to attenuate pain, whether urge-to-cough, a
      respiratory sensation preceding cough, exerts a similar inhibitory effect on pain
      has not been clarified. We examined the effects of both urge-to-cough and dyspnea
      on pain induced by thermal noxious stimuli. Urge-to-cough was induced by citric
      acid challenge and dyspnea was induced by external inspiratory resistive loads.
      During inductions of two respiratory sensations, perception of pain was assessed
      by thermal pain threshold (TPTh) and tolerance (TPTo). TPTh and TPTo were
      significantly increased accompanied by increases in perception of both urge-to
      cough and dyspnea. Fractional change in TPTh during dyspnea was significantly
      correlated with that during urge-to-cough. Fractional change in TPTo during
      dyspnea was significantly correlated with that during urge-to-cough. The study
      suggests that both two distinct respiratory sensations, i.e., urge-to-cough and
      dyspnea may harbor perception of pain. Further studies investigating interactions
      among these sensations in clinical settings are warranted.

PMID- 22465528
TI  - Monitoring endoplasmic reticulum stress responsive mRNAs by RNA sequencing.
AB  - Gene expression profile upon endoplasmic reticulum (ER) stress was analyzed by
      deep shotgun sequencing of mRNAs (DSSR) using RNAs from polysomes or cytoplasm of
      the HT29 cell. Two time points, 4h after tunicamycin treatment when IRE1alpha
      signaling pathway is active and 16h after the treatment when it is inactive, were
      used. There was a transient decrease in the proportion of shorter mRNA species
      (<1000bp) in polysome, while it increased transiently in the cytoplasm. Despite
      such an overall change and decrease in total amount of polysomes, the majority of
      the 6966 genes analyzed had less than 2 fold change in their expressions. We
      searched for the genes whose expression was elevated by 2 folds or more in both
      polysome and cytoplasm and confirmed the results with RT-PCR. There were 7 genes
      elevated only at 4h (Group I), 20 genes only at 16h (Group II) and 7 genes both
      at 4 and 16h (Group III). There were 3 genes involved in ribosomal RNA biogenesis
      in Group I and 2 genes involved mTOR control in Group III. This was consistent
      with the concept that the ribosome is the essential site for managing ER stress.
      DSSR is a useful tool for the search of candidates of ER stress responsive genes.

PMID- 22465529
TI  - Molecular cloning and characterisation of ovine dual oxidase 2.
AB  - The dual oxidases (DUOX1 and DUOX2) are NADPH-dependent hydrogen peroxide
      producing enzymes that are reported to function in a physiological capacity and
      as a component of the mucosal immune response. We have previously reported
      increased expression of the DUOX2 gene in the gut mucosa of sheep in response to
      gastrointestinal nematode (GIN) challenge. In this paper, we report the cloning
      of the full-length ovine DUOX2 transcript, using a PCR based strategy. The ovine
      DUOX2 transcript includes an ORF of 4644 bases, and encodes a protein with 97%
      identity to the bovine sequence. We also cloned a fragment of DUOX1 (encompassing
      nucleotides 2692-2829), and the proximal promoter sequence of DUOX2. Through
      analysis of sequence data we have confirmed that DUOX1 and DUOX2 are co-located
      in a head to tail arrangement conserved across many species. Alignment of the
      sequences to the ovine genome predicts a location of this gene cluster on ovine
      chromosome 7. We quantified the expression of ovine DUOX1 and DUOX2 transcripts
      in 24 different sheep tissues, and discovered tissue specific expression
      signatures. DUOX2 was found to be most highly expressed in tissues of the
      gastrointestinal tract, while expression of DUOX1 predominated in the bladder.
      Rapid amplification of cDNA ends (RACE) analysis identified the existence of
      multiple 5' UTR variants in DUOX2, ranging in size from 32 to 242 nucleotides,
      with 3 distinct transcribed regions. Real time PCR quantification of the DUOX2
      UTR variants revealed that these were differentially expressed between tissues,
      and at various stages of the response to GIN parasite infection. The collective
      evidence suggested a complex regulation of DUOX2, prompting a bioinformatic
      analysis of the proximal promoter regions of ovine DUOX2 to identify potential
      transcription factor binding sites (TFBS) that may explain the differences in the
      observed expression of the transcript variants of DUOX2. Possible transcription
      factor families that may regulate this process were identified as Kruppel-like
      factors (KLF), ETS-factors, erythroid growth receptor factors (EGRF) and myogenic
      differentiation factors (MYOD).

PMID- 22465530
TI  - A non-LTR retroelement extinction in Spermophilus tridecemlineatus.
AB  - The typical mammalian genome is dominated by two types of transposable elements
      (TEs), the autonomous and non-autonomous non-LTR retrotransposons, i.e. LINEs and
      SINEs, and with few exceptions there is a sole active LINE family (L1). During an
      ongoing investigation of TEs in rodents we determined that overall transposon
      activity has been steadily declining in Spermophilus tridecemlineatus. More
      specifically, the typically ubiquitous L1 activity of mammals has decreased
      drastically within the last 26MY. Indeed, only three L1 insertions with intact
      ORF1 sequences were readily identifiable and no intact ORF2 sequences were
      identified. The last L1 and SINE insertions date to ~5.3MYA and 4MYA,
      respectively. Based on our inability to computationally identify recently
      inserted L1 elements we suggest that S. tridecemlineatus is experiencing a
      quiescence or extinction of non-LTR retrotransposon activity. Such a finding
      represents only the fourth instance of a loss of non-LTR retrotransposon activity
      identified in mammals and, as such, represents an important additional data point
      to guide our understanding of LINE dynamics in eutherians.

PMID- 22465531
TI  - Two genetic variants in FABP1 and susceptibility to non-alcohol fatty liver
      disease in a Chinese population.
AB  - Liver fatty acid-binding protein (FABP1) serves as a key regulator of hepatic
      lipid metabolism, and polymorphisms within the FABP1 gene have been associated
      with several metabolic traits. To investigate the association between FABP1
      polymorphisms and the risk of non-alcohol fatty liver disease (NAFLD) in a
      Chinese population, the genotypes and haplotypes of FABP1 (rs2241883 T/C and
      rs1545224G/A) were determined in 553 patients with NAFLD and 553 healthy
      controls. The results showed that individuals with at least one copy of the
      rs2241883 C allele (TC or CC genotype) had an elevated risk for developing NAFLD
      (odds ratio [OR]=1.32, 95% CI: 1.01-1.71), and individuals with at least one copy
      of the rs1545224 A allele (GA or AA genotype) also had a significantly increased
      risk for NAFLD (OR=1.52, 95% CI: 1.14-2.02). Cumulative effect analysis of the
      two SNPs revealed that individuals with two risk genotypes were at significantly
      higher risk of NAFLD than those without risk genotype, and a significant trend of
      increased risk with increasing numbers of risk genotype was observed.
      Stratification analysis showed that the rs2241883 C allele carriers had higher
      level of LDL-C and the rs1545224 A allele carriers had higher level of FPG than
      those without this allele. In addition, haplotype analysis revealed that the one
      composed of the rs1545224 A and rs2241883 C variants was significantly associated
      with an increased risk for NAFLD (OR=1.34; 95% CI=1.05-1.40) compared to the GT
      haplotype. Taken together, the present study suggests that genetic variations
      within FABP1 influence susceptibility to NAFLD independently or jointly.

PMID- 22465532
TI  - Telomere shortening in women resident close to waste landfill sites.
AB  - Several studies demonstrate links between environmental stress and index of
      reduced health, including risk factors for cardiovascular disease, reduced immune
      function and cancer risks. We investigated the hypothesis that pollution, as an
      environmental stress, impacts health by modulating the rate of cellular aging in
      healthy pregnant women. Our research looked at the effects that illegal waste
      sites have on the localized population of pregnant women in Campania, Italy. As
      is often the case in illegal dumping, the effects on the population are often
      seen well before knowing what specific agents in the soil and water are
      responsible. Here we provide evidence that the pollution in this region is
      significantly associated with higher oxidative stress, shorter telomere length
      and lower telomerase activity, which are known determinants of cell senescence
      and aging-related meiotic dysfunction in women, in peripheral blood mononuclear
      cells from healthy pregnant women, subjected to therapeutic abortion in the
      second trimester of pregnancy. These findings may have implications for
      understanding how, at the cellular level, environmental stress may promote
      earlier onset of age-related diseases.

PMID- 22465533
TI  - Genetic analysis of the TBX20 gene promoter region in patients with ventricular
      septal defects.
AB  - Congenital heart disease (CHD) is the most common human birth defect. The
      morbidity and mortality of CHD patients are significantly higher than normal
      population even after surgical correction of cardiac defects, which is likely
      caused by genetic defects. To date, genetic causes for CHD remain largely
      unknown. TBX20 gene encodes a T-box transcription factor that plays pivotal roles
      in cardiac morphogenesis and is required for maintaining adult heart function and
      maturation. Mutations in TBX20 gene have been reported in familiar and sporadic
      CHD patients. However, the promoter region of TBX20 gene has not been genetically
      analyzed in CHD patients. As TBX20 functions as a dosage-dependent regulator
      during the heart development, we hypothesized that the sequence variants within
      the promoter region of the TBX20 gene may contribute to CHD. In this study, we bi
      directionally sequenced the promoter region of the TBX20 gene in 265 patients
      with ventricular septal defects (VSD) and 242 controls. Within the promoter
      region of the TBX20 gene, one single-nucleotide polymorphism (SNP), rs336284
      (g.4740T>C), and one novel heterozygous variant g.4741 G>A, which was linked with
      rs336284 (g.4740 T>C), were found in both VSD patients and controls with similar
      frequencies. A novel heterozygous variant, g.4932 G>A, was found in one VSD
      patient, but in none of controls, which significantly inhibited the
      transcriptional activities of TBX20 gene promoter, suggesting that the variant
      may contribute to the VSD etiology. Therefore, our data provides new information
      with respect to TBX20 gene mutations in CHD patients.

PMID- 22465534
TI  - Characterization and expression analysis of AcSERK2, a somatic embryogenesis and
      stress resistance related gene in pineapple.
AB  - The isolation and characterization of AcSERK2, another somatic embryogenesis
      receptor-like kinase (SERK) gene homolog, confirmed that there was a SERK gene
      family in pineapple. AcSERK2 shared high similarity to AcSERK1 and other SERKs,
      containing all the characteristic domains of the SERK family. The expressed
      recombinant protein of pET-AcSERK2 was soluble. AcSERK2 expression was
      effectively induced by 2,4-dichlorophenoxyacetic acid (2,4-D) and maintained in
      high level at the early stage of somatic embryogenesis (SE). The results of in
      situ hybridization showed that AcSERK2 expressed at high level in the competent
      cells under the induction of 2, 4-D and at low level during the development of
      meristematic center to globular embryo. This indicated that AcSERK2 could be used
      as a potential marker gene to monitor the acquisition of embryogenic competence.
      However, AcSERK2 expression was also detected in all the tested organs and the
      expression level decreased along with the development of calyx, ovule and ovary.
      These results suggested that AcSERK2 maybe play a broader role in organ
      development. AcSERK2 transcription could be induced by exogenous hormones and
      abiotic stress. It was deduced that AcSERK2 may participate in response to
      exogenous hormones and abiotic stress regulation in pineapple. The expression
      pattern of AcSERK2 during SE differed from that of AcSERK1, and this indicated
      that the SERK genes may be non-redundant in somatic embryogenesis.

PMID- 22465535
TI  - Development and characterization of cell culture systems from Puntius (Tor)
      chelynoides (McClelland).
AB  - Puntius (Tor) chelynoides, commonly known as dark mahseer, is a commercially
      important coldwater fish species which inhabits fast-flowing hill-streams of
      India and Nepal. Cell culture systems were developed from eye, fin, heart and
      swim bladder tissues of P. chelynoides using explant method. The cell culture
      system developed from eye has been maintained towards a continuous cell line
      designated as PCE. The cells were grown in 25cm(2) tissue culture flasks with
      Leibovitz' L-15 media supplemented with 20 % fetal bovine serum (FBS) at 24
      degrees C. The PCE cell line consists of predominantly fibroblast-like cells and
      showed high plating efficiency. The monolayer formed from the fin and heart
      explants were comprised of epithelial as well as fibroblast-like cells, a
      prominent and rhythmic heartbeat was also observed in heart explants. Monolayer
      formed from swim bladder explants showed the morphology of fibroblast-like cells.
      All the cells from different tissues are able to grow at an optimum temperature
      of 24 degrees C and growth rate increased as the FBS concentration increased. The
      PCE cell line was characterized using amplification of mitochondrial cytochrome
      oxidase subunit I (COI) & 16S rRNA genes which confirmed that the cell line
      originated from P. chelynoides. Cytogenetic analysis of PCE cell line and cells
      from fin revealed a diploid count of 100 chromosomes. Upon transfection with
      pEGFP-C1 plasmid, bright fluorescent signals were observed, suggesting that this
      cell line can be used for transgenic and genetic manipulation studies. Further,
      genotoxicity assessment of PCE cells illustrated the utility of this cell line as
      an in vitro model for aquatic toxicological studies. The PCE cell line was
      successfully cryopreserved and revived at different passage levels. The cell line
      and culture systems are being maintained to develop continuous cell lines for
      further studies.

PMID- 22465536
TI  - Comprehensive DNA copy number profile and BAC library construction of an Indian
      individual.
AB  - Bacterial artificial chromosomes (BACs) are used in genomic variation studies due
      to their capacity to carry a large insert, their high clonal stability, low rate
      of chimerism and ease of manipulation. In the present study, an attempt was made
      to create the first genomic BAC library of an anonymous Indian male (IMBL4)
      consisting of 100,224 clones covering the human genome more than three times.
      Restriction mapping of 255 BAC clones by pulse field gel electrophoresis
      confirmed an average insert size of 120 kb. The library was screened by PCR using
      SHANK3 (SH3 and multiple ankyrin repeat domains 3) and OLFM3 (olfactomedin 3)
      specific primers. A selection of clones was analyzed by fluorescent in situ
      hybridization (FISH) and sequencing. Fine mapping of copy number variable regions
      by array based comparative genomic hybridization identified 467 CNVRs in the
      IMBL4 genome. The IMBL4 BAC library represents the first cataloged Indian genome
      resource for applications in basic and clinical research.

PMID- 22465537
TI  - Life in cells, hosts, and vectors: parasite evolution across scales.
AB  - Parasite evolution is increasingly being recognized as one of the most important
      issues in applied evolutionary biology. Understanding how parasites maximize
      fitness whilst facing the diverse challenges of living in cells, hosts, and
      vectors, is central to disease control and offers a novel testing ground for
      evolutionary theory. The Centre for Immunity, Infection, and Evolution at the
      University of Edinburgh recently held a symposium to address the question "How do
      parasites maximise fitness across a range of biological scales?" The symposium
      brought together researchers whose work looks across scales and environments to
      understand why and how parasites 'do what they do', tying together mechanism,
      evolutionary explanations, and public health implications. With a broad range of
      speakers, our aim was to define and encourage more holistic approaches to
      studying parasite evolution. Here, we present a synthesis of the current state of
      affairs in parasite evolution, the research presented at the symposium, and
      insights gained through our discussions. We demonstrate that such
      interdisciplinary approaches are possible and identify key areas for future
      progress.

PMID- 22465538
TI  - The magnetic retina: light-dependent and trigeminal magnetoreception in migratory
      birds.
AB  - Recent advances have brought much new insight into the physiological mechanisms
      and required characteristics of the sensory molecules that enable birds to use
      magnetic fields for orientation. European robins almost certainly have two
      magnetodetection senses, one associated with the ophthalmic branch of the
      trigeminal nerve, and one based on light-dependent radical-pair processes in both
      eyes. The first brain areas processing magnetic information from each of these
      two senses have been identified. It has been experimentally verified that Earth
      strength magnetic fields can affect photo-induced chemical reactions and that
      these reactions can respond to magnetic field direction. Diagnostic behavioural
      experiments have provided clues to identify putative magnetoreceptive molecules
      in the retina. We discuss the implications of these and other recent findings and
      outline crucial open questions with an emphasis on the light-dependent mechanism.

PMID- 22465539
TI  - Echinococcus multilocularis in Svalbard, Norway: microsatellite genotyping to
      investigate the origin of a highly focal contamination.
AB  - Echinococcus multilocularis is a threatening cestode involved in the human
      alveolar echinococcosis. The parasite, mainly described in temperate regions of
      the Northern hemisphere was described for the first time in 1999 in the High
      Arctic Svalbard archipelago, Norway. The origin of this contamination could be
      due to an anthropogenic introduction from mainland Europe by domestic dogs or
      with the introduction of the sibling vole, perhaps from mainland Russia (St.
      Petersburg area), or with roaming Arctic foxes, known as the main definitive host
      of the parasite in Arctic regions. The genetic diversity of E. multilocularis in
      Svalbard was investigated here for the first time by genotyping using EmsB
      microsatellite and compared to other genotyped populations in the main worldwide
      endemic areas. We found low polymorphism amongst the 27 metacestode isolates from
      sibling voles trapped in the core of the distribution area of the vole on
      Svalbard. E. mutilocularis Arctic populations, using the Arctic fox as the
      definitive host, were genetically separated from European temperate populations
      that use the red fox, but closely related to St. Lawrence Island samples from
      Alaska. The result is inconsistent with the hypothesis of an anthropogenic
      introduction from mainland Europe, but can be seen as consistent with the
      hypothesis that Arctic foxes introduced E. multilocularis to Svalbard.

PMID- 22465540
TI  - Investigation of bistable perception with the "silhouette spinner": sit still,
      spin the dancer with your will.
AB  - Many studies have used static and non-biologically related stimuli to investigate
      bistable perception and found that the percept is usually dominated by their
      intrinsic nature with some influence of voluntary control from the viewer. Here
      we used a dynamic stimulus of a rotating human body, the silhouette spinner
      illusion, to investigate how the viewers' intentions may affect their percepts.
      In two experiments, we manipulated observer intention (active or passive),
      fixation position (body or feet), and spinning velocity (fast, medium, or slow).
      Our results showed that the normalized alternating rate between two bistable
      percepts was greater when (1) participants actively attempted to switch percepts,
      (2) when participants fixated at the spinner's feet rather than the body,
      inducing as many as 25 switches of the bistable percepts within 1 min, and (3)
      when they watched the spinner at high velocity. These results suggest that a
      dynamic biologically-bistable percept can be quickly alternated by the viewers'
      intention. Furthermore, the higher alternating rate in the feet condition
      compared to the body condition suggests a role for biological meaningfulness in
      determining bistable percepts, where 'biologically plausible' interpretations are
      favored by the visual system.

PMID- 22465541
TI  - When is spatial filtering enough? Investigation of brightness and lightness
      perception in stimuli containing a visible illumination component.
AB  - Brightness (perceived intensity) and lightness (perceived reflectance) matching
      were investigated in seven well-known visual stimuli that contain a visible
      shadow or transparent overlay. These stimuli are frequently upheld as evidence
      that low-level spatial filtering is inadequate to explain brightness/lightness
      illusions and that additional mid- or high-level mechanisms are required. The
      argument in favor of rejecting low-level spatial filtering explanations has been
      founded on the erroneous assumption that equating test patch and near surround
      luminance is sufficient to control for and rule out this type of mechanism. We
      tested this idea by comparing the matching behavior of four observers to the
      predictions of the ODOG multiscale filtering model (Blakeslee & McCourt, 1999).
      Lightness and brightness matching differed significantly only when test patches
      appeared in shadow or beneath a transparency. Lightness and brightness matches
      were both significantly larger under these conditions; however, the lightness
      matches greatly exceeded the brightness matches. Lightness matches were greater
      for test patches in shadow or beneath a transparency because lightness matches
      under these conditions were based on conscious inferential (not sensory-level)
      judgments where observers attempted to discount the difference in illumination.
      The ODOG model accounted for approximately 80% of the total variance in the
      brightness matches (as well as in the lightness matches for targets not in shadow
      or beneath a transparency), and successfully predicted the relative magnitude of
      these matches in five of the seven stimulus sets. These results indicate that
      multiscale spatial filtering provides a unified and parsimonious explanation for
      brightness perception in these stimuli and imply that higher-level mechanisms are
      not required to explain them. The model was not as successful for the argyle and
      wall of blocks illusions in that it incorrectly rank-ordered the relative
      magnitude of the effects across different versions of the stimuli. It is an
      important question whether such model failures are due to known but corrigible
      limitations of the ODOG model or whether they will require other (possibly higher
      level) explanations.

PMID- 22465542
TI  - Fibrocytes: emerging effector cells in chronic inflammation.
AB  - Fibrocytes are unique cells possessing the proinflammatory properties of
      macrophages and the tissue remodeling properties of fibroblasts. Because these
      cells display a strong association with many human diseases characterized by
      chronic and dysregulated inflammatory responses the study of fibrocytes is
      important and timely. This review presents recent data regarding fibrocyte
      origin, identification, differentiation, and appearance in diseased tissue. The
      available data regarding the association of fibrocytes with several forms of
      chronic tissue inflammation seen in the setting of lung disease, autoimmunity,
      liver disease, and normal aging will be presented. This review concludes by
      putting these data in perspective and by suggesting future areas of
      investigation. It is hoped that this information will lead to additional
      investigations in this burgeoning field and improve our understanding of the
      novel role fibrocytes may play in human disease.

PMID- 22465543
TI  - Organic nanocarriers for cancer drug delivery.
AB  - A major focus in translational cancer research is the study of nanocarriers as
      novel delivery systems for chemotherapeutics. Organic vesicular nanocarriers,
      such as liposomes and micelles, have the advantage of low toxicity and the
      versatility to carry diverse drugs and conjugate to targeting agents. This offers
      the potential for combining treatment and diagnosis (theranostics). Successful
      incorporation into these nanoformulations has been demonstrated for classical
      chemotherapeutic drugs that are mostly hydrophobic, small interfering RNA,
      biological therapeutics and specific nanoparticles, such as superparamagnetic
      nanoparticles. Liposomes and micelles appear to take advantage of the enhanced
      permeability and retention (EPR) effect in solid tumours to increase accumulation
      at the target site (passive targeting). This translates to the clinic, where
      liposomal drug formulations are reported to exhibit higher efficacy and less side
      effects. Multidrug formulations and combinations with other treatments, for
      example, radiation or radiofrequency ablation, to trigger drug release from the
      nanocarrier at the target site, are mostly at the pre-clinical stage. More
      complex formulations that incorporate treatment agents together with targeting
      (active targeting) and imaging molecules have also been investigated in in vivo
      models with encouraging results.

PMID- 22465544
TI  - Opposing effects on the phrenic motor pathway attributed to dopamine-D1 and 
      D3/D2 receptor activation.
AB  - Previous in vivo studies revealed that dopamine-D1-agonists elevate excitability
      of ventral respiratory column (VRC) neurons and increase discharge activity in
      the phrenic motor output through actions in the brainstem. In this in vivo study
      performed on pentobarbital-anesthetized cats, we show that D1-agonists (SKF
      38393, dihydrexidine) given intravenously enhanced discharge activity in VRC
      inspiratory neurons and the phrenic nerve in two stages; discharge intensity
      first increased to a peak and then discharge duration increased. Cross
      correlation analysis of VRC inspiratory neuron and phrenic nerve discharges
      showed that both stages increased strength of coupling between medullary
      inspiratory neurons and the phrenic motoneuron output. Intracellular recording
      and microiontophoresis experiments indicated that D1-agonists produced their
      stimulatory effects indirectly through actions on synaptic inputs to VRC
      inspiratory neurons. Because other laboratories have provided evidence that
      dopamine acting on other types of receptors depresses respiratory neuron
      excitability we tested the effects of piribedil, an agonist that activates
      receptors of the generally depressant D3/D2-dopamine receptor family, on phrenic
      nerve activity. Piribedil depressed phrenic nerve inspiratory discharge
      intensity, prolonged discharge duration, slowed burst frequency and slowed rate
      of action potential augmentation. The effects of piribedil were partially
      counteracted by intravenous injection of dihydrexidine. We propose that under
      normal, steady state conditions, D1-receptor-mediated excitatory modulation of
      phrenic motor output overrides D3/D2-receptor mediated inhibition.

PMID- 22465545
TI  - The influence of varying inspired fractions of O2 and CO2 on the development of
      involuntary breathing movements during maximal apnoea.
AB  - The growing urge to breathe that occurs during breath-holding results in
      development of involuntary breathing movements (IBMs). The present study
      determined whether IBMs are initiated at critical levels of hypercapnia and/or
      hypoxia during maximal apnoea. Arterial blood gasses at the onset of IBM were
      monitored during maximal voluntary breath-holds. Eleven healthy men performed
      breath holds after breathing air, hyperoxic-normocapnia, hypoxic-normocapnia, and
      normoxic-hypercapnia. Pre-breathing of the gas mixtures facilitated the IBM
      onset, reducing the time-to-onset for ~46% (hyperoxic condition) and for ~80%
      (hypoxic condition) compared to the normoxic air breathing time. A strong
      correlation (R=0.83, P=0.002) between arterial partial pressure of CO2 (PaCO2) at
      IBM onset after pre-breathing hyperoxic and hypercapnic gas mixtures was
      observed, suggesting the existence of a possible IBM PaCO2 threshold level of
      ~6.5 +/- 0.5 kPa. No clear "threshold" was observed for partial pressure of
      arterial O2(PaO2). However, we observed that IBM onset was influenced, in part,
      by an interaction between PaO2 and PaCO2 levels during maximal apnoea. This study
      demonstrated the complex interaction between arterial blood-gases and the
      physiological response to maximal breath holding.

PMID- 22465546
TI  - Emodin loaded solid lipid nanoparticles: preparation, characterization and
      antitumor activity studies.
AB  - The objective of the present study was to prepare and characterize emodin (EMO)
      loaded solid lipid nanoparticles (E-SLNs) and evaluate their antitumor activity
      in vitro. EMO and pharmaceutical lipid material were used to prepare E-SLNs by
      high pressure homogenization (HPH). Poloxamer 188 and Tween 80 were used as
      surfactants. The physicochemical properties of the E-SLNs were investigated by
      particle size analysis, zeta potential measurement, drug entrapment efficiency
      (EE), stability and in vitro drug release behavior. The E-SLNs showed stable
      particle size at 28.6 +/- 3.1 nm, ideal drug EE and relative long-term physical
      stability after being stored for 4 months. The drug release of E-SLNs could last
      72 h and exhibited a sustained profile, which made it a promising vehicle for
      oral drug delivery. MTT assay showed that E-SLNs could significantly enhance the
      in vitro cytotoxicity against human breast cancer cell line MCF-7 and MDA-MB-231
      cells compared to the EMO solution, while free EMO, blank SLNs (B-SLNs) and E
      SLNs all showed no significant toxicity to human mammary epithelial line MCF-10A
      cells. Flow cytometric analysis demonstrated that E-SLNs also showed more
      significant cell cycle arrest effect in MCF-7 cells compared to bulk EMO
      solution. Hoechst 33342 staining and Annexin V-FITC/PI double staining further
      confirmed that E-SLNs induced higher apoptotic rates in MCF-7 cells, indicating
      that cell cycle arrest and apoptosis maybe the underlying mechanism of the
      enhanced cytotoxicity. Taken together, it seems that HPH was a simple, available
      and effective method for preparing high quality E-SLNs to enhance its aqueous
      solubility. Moreover, these results suggest that the delivery of EMO as lipid
      nanoparticles maybe a promising approach for cancer therapy.

PMID- 22465547
TI  - Evaluation of the OSCAR system for the production of monoclonal antibodies by CHO
      K1 cells.
AB  - Biopharmaceutical production of complex recombinant protein therapeutics
      currently relies on mammalian cells. The development of high-yielding stable cell
      lines requires processes of transfection, selection and adaptation. With several
      technologies available, selection has been most frequently based on dihydrofolate
      reductase or glutamine synthetase systems, which can be very time-consuming. Due
      to the pressure to reduce development costs and speed up time to market, new
      technologies are emerging, as the promising OSCAR expression system that could
      provide more rapid development of high-yielding stable cell lines than the
      traditional systems. However, further evaluation of its application in a wider
      range of cell types and media is still necessary. In this study, application of
      OSCAR for the transfection of a CHO-K1 cell line with a monoclonal antibody was
      evaluated. OSCAR was reasonably fast and simple, without negative impact on cell
      growth characteristics. However, minigene selection was critical, with only
      pDWM128 working for the cell line assessed. Initial relatively high levels of
      production decreased significantly in the first few weeks of passing, remaining
      relatively stable although with low yield thereafter. The results suggest that
      more work is required to develop methodologies and prove that OSCAR has
      significant value to the bioproduction industry.

PMID- 22465548
TI  - Solid lipid nanoparticles as intracellular drug transporters: an investigation of
      the uptake mechanism and pathway.
AB  - The aim of this work was to develop a systematic analysis of the cellular
      internalisation mechanism and pathway of solid lipid nanoparticles (SLN)
      internalisation. To evaluate if SLN show cell uptake and to understand the
      mechanism of internalisation, four human glioma cell lines (A172, U251, U373 and
      U87) and a human macrophage cell line (THP1) were used. For this purpose
      rhodamine 123 (R123) was loaded into SLN coated with polysorbate 60 and 80.
      Fluorescence microscopy and flow cell cytometry techniques were assessed to study
      internalisation of these systems within the cells. MTT studies were performed to
      evaluate the cytotoxicity of the R123-loaded SLN. To assess the SLN
      internalisation mechanism and intracellular pathway, excluding endocytosis
      mechanisms were applied. Our results revealed that R123-loaded SLN with mean size
      below 200 nm and slight negative surface charge (around -20 mV) have the ability
      to be internalised by gliomas in a higher amount than by macrophages. The
      mechanism of internalisation was found to be mainly through a clathrin-dependent
      endocytic pathway. In addition, the cytotoxicity of SLN was higher for gliomas
      than for macrophages. These results suggest that SLN can be a promising
      alternative in brain tumours treatment.

PMID- 22465549
TI  - Spray-dried nanofibrillar cellulose microparticles for sustained drug release.
AB  - Nanofibrillar cellulose (also referred to as cellulose nanofibers, nanocellulose,
      microfibrillated or nanofibrillated cellulose) has gained a lot of attention in
      recent years in different research areas including biomedical applications. In
      this study we have evaluated the applicability of nanofibrillar cellulose (NFC)
      as a material for the formation of matrix systems for sustained drug delivery.
      For that purpose, drug loaded NFC microparticles were produced by a spray drying
      method. The microparticles were characterized in terms of size and morphology,
      total drug loading, and physical state of the encapsulated drug. Drug release
      from the microparticles was assessed by dissolution tests, and suitable
      mathematical models were used to explain the drug releasing kinetics. The
      particles had spherical shapes with diameters of around 5 MUm; the encapsulated
      drug was mainly in amorphous form. The controlled drug release was achieved. The
      drug releasing curves were fitted to a mathematical model describing the drug
      releasing kinetics from a spherical matrix. Different drugs had different release
      kinetics, which was a consequence of several factors, including different
      solubilities of the drugs in the chosen medium and different affinities of the
      drugs to the NFC. It can be concluded that NFC microparticles can sustain drug
      release by forming a tight fiber network and thus limit drug diffusion from the
      system.

PMID- 22465550
TI  - Predicting the solubility-permeability interplay when using cyclodextrins in
      solubility-enabling formulations: model validation.
AB  - Although the extraordinary solubility advantage afforded by cyclodextrins has led
      to their widespread use as pharmaceutical solubilizers, several reports have
      emerged that cyclodextrins may also reduce the apparent permeability of the drug.
      With the purpose to investigate this solubility-permeability interplay, we have
      recently developed a mathematical mass transport model that quantitatively
      explains the impact of molecular complexation on the intestinal permeability.
      This model enabled excellent quantitative prediction of progesterone P(eff) as a
      function of HPbetaCD concentrations in several experimental methods. The purpose
      of the present study was to challenge the predictive capabilities of this
      mathematical model, assessing whether the model allows the prediction of
      literature permeability data, as a model validation method. The mass-transport
      model was applied to carbamazepine and hydrocortisone, and the predicted
      permeability (P(eff), P(m) and P(aq)) vs. HPbetaCD concentration were plotted.
      Excellent agreement was obtained between literature experimental permeability and
      the predicted P(eff) values for both compounds at all of the HPbetaCD
      concentrations tested. The presented validated model that considers the opposing
      effects of the formulation on the solubility and the permeability, can lead to a
      more efficient and intelligent use of molecular complexation strategies; the
      formulator will be able to a priori strike the optimal solubility-permeability
      balance to maximize and facilitate the overall oral drug absorption.

PMID- 22465551
TI  - Endoscopically assisted decompression for pronator syndrome.
AB  - PURPOSE: Traditional surgical management for pronator syndrome results in a
      relatively long and possibly disfiguring scar across the antecubital fossa. The
      purposes of this study were to present an endoscopic technique that facilitates
      the decompression of the proximal median nerve without extensile incisions, and
      to evaluate whether this minimally invasive procedure could adequately and safely
      treat the condition to improve outcome scores. METHODS: We treated 13 patients
      (14 cases) with isolated pronator syndrome with endoscopically assisted
      decompression and retrospectively reviewed them. We excluded patients with
      concomitant carpal tunnel syndrome or other compression neuropathies. The average
      age of the patient at presentation was 41 years. Final follow-up averaged 22
      months. We asked all patients to rate their preoperative and postoperative
      condition and functional capabilities using the validated Disabilities of the
      Shoulder, Arm, and Hand (DASH) scoring protocol. RESULTS: All 13 patients
      improved symptomatically as reflected in the DASH score assessment. The
      preoperative scores averaged 56 and the postoperative scores were significantly
      reduced and averaged 6. There were 3 minor complications, which resolved
      spontaneously. CONCLUSIONS: The endoscopically assisted, minimally invasive
      approach to treat pronator syndrome adequately and safely decompressed all
      anatomical points of compression and improved DASH scores. This may reduce
      morbidity and facilitate a quicker recovery compared with the traditional open
      incision techniques. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22465552
TI  - Endovascular treatment of acute and chronic aortic pathology in patients with
      Marfan syndrome.
AB  - BACKGROUND: In patients with Marfan syndrome, the complications of aortic
      degeneration, including dissection, aneurysm, and rupture represent the main
      cause of mortality. Although contemporary management of ascending aortic disease
      requires open surgical reconstruction, endovascular repair is now available for
      management of descending thoracic and abdominal aortic pathology (ie, thoracic
      endovascular aortic repair [TEVAR], endovascular aneurysm repair [EVAR]). The
      short- and long-term benefit of endovascular repair in Marfan patients remains
      largely unproven. We examine our outcomes after EVAR in this patient population.
      METHODS: All patients with a diagnosis of Marfan syndrome who were treated with
      TEVAR/EVAR were evaluated in a retrospective review. Perioperative, procedure
      specific and patient covariate data were aggregated. Primary endpoints were
      overall mortality and procedural success as divided into three categories: (1)
      successful therapy, (2) primary failure, or (3) secondary failure. RESULTS:
      Between 2000 and June 2010, 16 patients were identified as having undergone 19
      TEVAR/EVAR procedures. These included three emergent operations (two for acute
      dissection/malperfusion and one for anastomotic disruption early after open
      repair). All 16 patients had previously undergone at least one (range, 1-5) open
      operation of the ascending aorta or arch at a time interval from 33 years to 1
      week prior to the index endovascular repair. During a median follow-up of 9.3
      months (range, 0-46 months), there were four deaths (25%). Six patients (38%) had
      successful endovascular interventions. Despite early success, there was one death
      in this group at 1 month postintervention. Seven patients (44%) experienced
      primary treatment failure with five undergoing open conversion and one undergoing
      left subclavian coil embolization (the seventh was lost to follow-up and
      presented 4 months later in cardiac arrest and expired without repair). There
      were three deaths in the primary treatment failure group. Two patients
      experienced secondary treatment failure. One underwent the index TEVAR for acute
      dissection with malperfusion and required a subsequent TEVAR for more distal
      aortic pathology. He is stable without disease progression. The other patient
      underwent open conversion after a second EVAR with four-vessel "chimney" stent
      grafts and is stable with his entire native aorta having been replaced.
      CONCLUSIONS: Aortic disease associated with Marfan syndrome is a complex clinical
      problem and many patients require remedial procedures. Endovascular therapy can
      provide a useful adjunct or bridge to open surgical treatment in selected
      patients. However, failure of endovascular therapy is common, and its use should
      be judicious with close follow-up to avoid delay if open surgical repair is
      required.

PMID- 22465554
TI  - Sertoli cell proliferation in the adult testis is induced by unilateral
      gonadectomy in African catfish.
AB  - Survival and development of male germ cells depends on their close contact with
      Sertoli cells. In the cystic spermatogenesis found in fish, one germ cell clone,
      initially a single undifferentiated spermatogonium type A, is enclosed by and
      accompanied through spermatogenesis by a group of Sertoli cells. Previous work
      showed that after forming such spermatogenic cysts, Sertoli cells proliferated
      mainly during the mitotic expansion of the spermatogonial clone in the cyst.
      Here, we used unilateral gonadectomy (ULG) as experimental model to study Sertoli
      cell proliferation at the start of cyst development in adult African catfish
      testis. Four days after surgery, we observed a particularly strong increase in
      the number of mitotic Sertoli cells along with a significant increase in the
      number of mitotic single type A spermatogonia. Proliferation of pairs of
      spermatogonia or of larger germ cell clones, however, did not change. At the same
      time, pituitary transcript levels of the three gonadotropin-subunits (cga,
      glycoprotein hormones, alpha polypeptide; fshb, follicle stimulating hormone,
      beta polypeptide; lhb, luteinizing hormone, beta polypeptide) were not different
      between sham-operated and ULG males. However, expression of the gonadotropin
      releasing hormone receptor gene gnrhr1 was significantly reduced after ULG, and
      Lh plasma levels were slightly elevated. In the testis remaining after ULG, Fsh
      receptor (fshr) mRNA levels increased significantly but luteinizing
      hormone/choriogonadotropin receptor (lhcgr) mRNA levels did not change.
      Circulating androgen levels did not differ between groups, but testicular
      androgen release increased significantly 2- to 3-fold after ULG. Considering the
      strong steroidogenic potency of Fsh and the expression of the fshr gene by Leydig
      cells in catfish, we explain the absence of an effect of ULG on circulating
      androgen levels by an Fshr-mediated, compensatory increase in the steroid
      production of the remaining testis, perhaps supported in addition by the
      increased Lh plasma levels. Since Fsh is a major stimulator of mammalian Sertoli
      cell proliferation, we propose that ULG-induced activation of the Fsh signalling
      system also promoted Sertoli cell proliferation and - possibly as a consequence
      of that - proliferation of single type A spermatogonia, providing the basis for
      an increased spermatogenic capacity.

PMID- 22465555
TI  - Diagnosis and management of brain and spinal cord tumors in the neonate.
AB  - Congenital central nervous system (CNS) tumors are rare, accounting for <5% of
      childhood CNS tumors. Although the definition remains arbitrary, 'congenital' is
      often defined as CNS tumors diagnosed at birth or within a few months after
      birth. Congenital CNS tumors are now increasingly detected on prenatal
      ultrasound, with polyhydramnios as the most frequent finding. After delivery,
      most congenital CNS tumors are associated with macrocrania and hydrocephalus.
      Teratomas are the most common congenital CNS tumors; other common tumors include
      astrocytomas, embryonal tumors such as medulloblastomas, and choroid plexus
      tumors. Choroid plexus tumors (predominantly papillomas) have the best outcome,
      as aggressive surgical resection can be curative. Other congenital CNS tumors
      have a collectively poor prognosis, although some subtypes may benefit from
      complete resections and chemotherapy. Given the rare incidences and diverse
      pathology of congenital CNS tumors, multicenter studies are required to
      accurately assess treatment efficacy and outcome measures.

PMID- 22465556
TI  - Reference values for Doppler velocimetry of the ophthalmic and central retinal
      arteries in low-risk pregnancy.
AB  - OBJECTIVE: To establish reference values for Doppler velocimetry of the
      ophthalmic artery (OA) and the central retinal artery (CRA) in low-risk
      pregnancy. METHOD: Between January 2008 and March 2009, 63 low-risk pregnant
      women underwent an ultrasound scan every 2 weeks at the Women's Hospital,
      Campinas, Brazil, to determine the resistance index (RI), pulsatility index (PI),
      and peak systolic velocity of both arteries, in addition to the flow velocity of
      the second peak and peak ratio (PR) of the OA. For analysis, linear regression
      was used with mixed models for longitudinal data, coefficient of determination,
      and estimates of the 5th and 95th percentiles for each parameter at each
      gestational age. Intra- and inter-observer variability was evaluated via the
      intraclass correlation coefficient. RESULTS: There was a trend of a reduction
      with gestational age in PI and RI of the OA, and PI of the CRA, but not in PR of
      the OA; and the respective reference values were established. Intra- and inter
      observer variability was considered satisfactory. CONCLUSION: Unilateral
      assessment of the orbital Doppler velocimetry is feasible. Establishment of
      reference values showed a negative correlation between gestational age and PI and
      RI of the OA, and PI of the CRA. The method demonstrated satisfactory
      reproducibility.

PMID- 22465557
TI  - Announcing the winner of the John J. Sciarra IJGO Prize Paper Award for 2011.

PMID- 22465558
TI  - Outcome of unintended pregnancy after ultrasound-guided high-intensity focused
      ultrasound ablation of uterine fibroids.
AB  - OBJECTIVE: To evaluate the safety of ultrasound-guided high-intensity focused
      ultrasound (USgHIFU) ablation of uterine fibroids among women with unintentional
      pregnancy within 1 year of therapy. METHODS: A retrospective analysis was
      conducted of 435 women who underwent USgHIFU therapy at Chongqing Medical
      University, China, between October 1, 2006, and October 1, 2009. RESULTS:
      Unplanned pregnancy was reported by 24 women within 1 year of USgHIFU ablation; 8
      of these women had desired pregnancy before undergoing treatment. A total of 27
      fibroids were detected, 24 of which were treated (mean volume 65.9+/-58.8 cm(3)).
      Pregnancy was continued by 7 women without any complications. One pregnant woman
      who had desired pregnancy before therapy underwent an induced abortion owing to
      concerns about the effects of USgHIFU on the fetus. Fourteen women without
      pregnancy intention before USgHIFU therapy chose to undergo induced abortion; 2
      women experienced spontaneous abortion. No adhesion occurred after USgHIFU
      therapy. Furthermore, USgHIFU, labor, and abortion had no effect on subsequent
      menstruation or sexual activities. CONCLUSION: Pregnancy within 1 year after
      USgHIFU ablation of uterine fibroids appears safe; however, large scale studies
      are required to confirm these data.

PMID- 22465559
TI  - Good Caco-2 cell culture practices.
AB  - The human Caco-2 cells differentiate spontaneously in culture forming monolayers
      of mature intestinal enterocytes which have been used as a model of the
      intestinal barrier for in vitro toxicology studies. Reproducibility problems
      often reported in literature have been generally ascribed to different culture
      related conditions, such as the type of animal serum used, the supplements added
      to the culture media, the passage number and the source of cell clones. The Caco
      2 cell culture protocol here described has been recently optimized in our
      laboratory, producing a homogeneous and highly polarized monolayer of cells which
      display many of the characteristics of the intestinal enterocytes. This protocol
      differs from standard protocols mainly because Caco-2 cells are subcultured when
      they reach just 50% of confluence, instead of 80%, retaining a high proliferation
      potential. When this cell population is seeded at high density on filter inserts
      differentiates almost synchronously and much more homogenously.

PMID- 22465560
TI  - Approaches for the preparation of non-linear amphiphilic polymers and their
      applications to drug delivery.
AB  - Amphiphilic polymers are particularly useful for drug delivery because of their
      ability to self-assemble into discrete aggregates. While this behavior has been
      studied in depth for simple linear block copolymer amphiphiles, recent advances
      in synthetic methodologies have provided efficient routes to amphiphilic polymers
      with more complex architecture, including dendrimers, hyperbranched polymers,
      star polymers, and cyclic polymers. These architectures can impart unique
      advantages, such as increased stability, on their micellar aggregates. Herein the
      different strategies for preparing these complex amphiphiles are described, and
      the application of their assemblies towards drug delivery are summarized.

PMID- 22465561
TI  - Predicting the absorption of chemical vapours.
AB  - The focus of this review is on the systemic absorption of vapours via skin,
      including experimental data as well as regression and pharmacokinetic models.
      Dermal contribution ratios (DCR), i.e. amount absorbed through skin relative to
      total intake (skin and inhalation) at specified conditions, could be identified
      or calculated from published data for 33 chemical vapours. The ratios vary from
      ~0.0002 (vinyl chloride) to ~0.8 (2-butoxyethanol), with hydrophilic chemicals
      having a higher ratio than lipophilic ones. Multiple regression analysis of these
      data suggests that the DCR is largely explained by the octanol:water partition
      coefficient, vapour pressure and molecular weight (R(2)=0.69). Several
      physiologically-based pharmacokinetic models were identified; however, all
      describe the absorption of single substances. Regarding predictive models, only
      two models were found. In conclusion, dermal uptake of chemical vapours needs
      more attention, as such exposures are common, data are scarce and few predictive
      models exist.

PMID- 22465563
TI  - Introduction to the pulmonary research group's symposium: Preclinical research in
      COPD and pulmonary fibrosis.

PMID- 22465564
TI  - Stimulus response latency of cough and expiration reflex depends on breathing in
      the rabbit.
AB  - Expiration reflex and cough may have distinct afferent pathways and/or central
      integrative mechanisms that may both result in different stimulus response
      latencies. A newly described method that uses a punctuate mechanical tracheal
      stimulus to provoke defensive ventilatory reflexes should allow the stimulus
      response latency to be calculated with reasonable accuracy. The aim of the study
      was to test whether cough and expiration reflex have different stimulus response
      latencies. Four hundred and sixty one mechanical tracheal stimulations (50-300
      msec) were performed in 21 anesthetized, tracheotomized rabbits. Twenty three
      percent stimulations (108) provoked a cough reflex and 37% an expiration reflex
      (171). The individual mean stimulus response latency was computed for each
      reflex, calculated from stimulus onset to earliest detectable change in
      ventilatory flow. Cough reflex latency was significantly shorter in inspiration
      compared to expiration (257+/-19 msec vs 391+/-61 msec; p=0.01). In contrast, the
      expiration reflex latency was significantly shorter in expiration compared to
      inspiration (210+/-11 msec vs 329+/-29 msec, p=0.003). It is concluded that the
      within breath dependence of the difference in stimulus response latency between
      cough and expiration reflex is more likely to express different brainstem
      mechanisms but difference in afferent fibres may not be excluded.

PMID- 22465565
TI  - Sweet taste and menthol increase cough reflex thresholds.
AB  - Cough is a vital protective reflex that is triggered by both mechanical and
      chemical stimuli. The current experiments explored how chemosensory stimuli
      modulate this important reflex. Cough thresholds were measured using a single
      inhalation capsaicin challenge. Experiment 1 examined the impact of sweet taste:
      Cough thresholds were measured after rinsing the mouth with a sucrose solution
      (sweet) or with water (control). Experiment 2 examined the impact of menthol:
      Cough thresholds were measured after inhaling headspace above a menthol solution
      (menthol vapor) or headspace above the mineral oil solvent (control). Experiment
      3 examined the impact of rinsing the mouth with a (bitter) sucrose octaacetate
      solution. Rinsing with sucrose and inhaling menthol vapor significantly increased
      measured cough thresholds. Rinsing with sucrose octaacete caused a non
      significant decrease in cough thresholds, an important demonstration of
      specificity. Decreases in cough reflex sensitivity from sucrose or menthol could
      help explain why cough syrups without pharmacologically active ingredients are
      often almost as effective as formulations with an added drug. Further, the
      results support the idea that adding menthol to cigarettes might make tobacco
      smoke more tolerable for beginning smokers, at least in part, by reducing the
      sensitivity of an important airway defense mechanism.

PMID- 22465566
TI  - Myotonic dystrophy type 1, daytime sleepiness and REM sleep dysregulation.
AB  - Myotonic dystrophy type 1 (DM1), or Steinert's disease, is the most common adult
      onset form of muscular dystrophy. DM1 also constitutes the neuromuscular
      condition with the most significant sleep disorders including excessive daytime
      sleepiness (EDS), central and obstructive sleep apneas, restless legs syndrome
      (RLS), periodic leg movements in wake (PLMW) and periodic leg movements in sleep
      (PLMS) as well as nocturnal and diurnal rapid eye movement (REM) sleep
      dysregulation. EDS is the most frequent non-muscular complaint in DM1, being
      present in about 70-80% of patients. Different phenotypes of sleep-related
      problems may mimic several sleep disorders, including idiopathic hypersomnia,
      narcolepsy without cataplexy, sleep apnea syndrome, and periodic leg movement
      disorder. Subjective and objective daytime sleepiness may be associated with the
      degree of muscular impairment. However, available evidence suggests that DM1
      related EDS is primarily caused by a central dysfunction of sleep regulation
      rather than by sleep fragmentation, sleep-related respiratory events or periodic
      leg movements. EDS also tends to persist despite successful treatment of sleep
      disordered breathing in DM1 patients. As EDS clearly impacts on physical and
      social functioning of DM1 patients, studies are needed to identify the best
      appropriate tools to identify hypersomnia, and clarify the indications for
      polysomnography (PSG) and multiple sleep latency test (MSLT) in DM1. In addition,
      further structured trials of assisted nocturnal ventilation and randomized trials
      of central nervous system (CNS) stimulant drugs in large samples of DM1 patients
      are required to optimally treat patients affected by this progressive, incurable
      condition.

PMID- 22465567
TI  - Susceptibility of Spodoptera frugiperda and S. exigua to Bacillus thuringiensis
      Vip3Aa insecticidal protein.
AB  - The Vip3Aa protein is an insecticidal protein secreted by Bacillus thuringiensis
      during the vegetative stage of growth. The activity of this protein has been
      tested after different steps/protocols of purification using Spodoptera
      frugiperda as a control insect. The results showed that the Vip3Aa protoxin was
      stable and retained full toxicity after being subjected to common biochemical
      steps used in protein purification. Bioassays with the protoxin in S. frugiperda
      and S. exigua showed pronounced differences in LC(50) values when mortality was
      measured at 7 vs. 10d. At 7d most live larvae were arrested in their development.
      LC(50) values of "functional mortality" (dead larvae plus larvae remaining in the
      first instar), measured at 7d, were similar or even lower than the LC(50) values
      of mortality at 10d. This strong growth inhibition was not observed when testing
      the trypsin-activated protein (62 kDa) in either species. S. exigua was less
      susceptible than S. frugiperda to the protoxin form, with LC(50) values around 10
      fold higher. However, both species were equally susceptible to the trypsin
      activated form. Processing of Vip3Aa protoxin to the activated form was faster
      with S. frugiperda midgut juice than with S. exigua midgut juice. The results
      strongly suggest that the differences in the rate of activation of the Vip3Aa
      protoxin between both species are the basis for the differences in susceptibility
      towards the protoxin form.

PMID- 22465568
TI  - Bonamia exitiosa (Haplosporidia) observed infecting the European flat oyster
      Ostrea edulis cultured on the Spanish Mediterranean coast.
AB  - Bonamia exitiosa and Bonamia ostreae are parasites that reproduce within the
      haemocytes of several oyster species. In Europe, the host species is the flat
      oyster Ostrea edulis. The parasite B. ostreae has been responsible for
      mortalities since the late 1970s throughout the European Atlantic coast. B.
      exitiosa was first detected, in 2007, on this continent in flat oysters cultured
      in Galicia (NW Spain). Since then, the parasite has also been detected in France,
      Italy and the United Kingdom. The bays of the Ebro Delta in the south of
      Catalonia represent the main bivalve culture area in the Mediterranean coast of
      Spain. Previous information from the area includes reports of several flat oyster
      pathogens, including the notifiable parasite Marteilia refringens. However, the
      status with regard to Bonamia parasites was uncertain. In the present study, a
      Bonamia parasite was observed in flat oysters cultured in the Alfacs Bay of the
      Ebro Delta by histology and real-time PCR. PCR-RFLP and sequencing suggested the
      presence of B. exitiosa. Finally, phylogenetic analyses of the studied Bonamia
      isolates corroborated B. exitiosa infection. M. refringens was also observed in
      the same oyster batch, and co-infection with both parasites was also detected.
      This is the first detection of B. exitiosa, in Catalonia and the Spanish
      Mediterranean coast. The impact of the parasite on the Mediterranean flat oyster
      activity needs to be urgently addressed.

PMID- 22465569
TI  - Genotypic variability and relationships between mite infestation levels, mite
      damage, grooming intensity, and removal of Varroa destructor mites in selected
      strains of worker honey bees (Apis mellifera L.).
AB  - The objective of this study was to demonstrate genotypic variability and analyze
      the relationships between the infestation levels of the parasitic mite Varroa
      destructor in honey bee (Apis mellifera) colonies, the rate of damage of fallen
      mites, and the intensity with which bees of different genotypes groom themselves
      to remove mites from their bodies. Sets of paired genotypes that are presumably
      susceptible and resistant to the varroa mite were compared at the colony level
      for number of mites falling on sticky papers and for proportion of damaged mites.
      They were also compared at the individual level for intensity of grooming and
      mite removal success. Bees from the "resistant" colonies had lower mite
      population rates (up to 15 fold) and higher percentages of damaged mites (up to 9
      fold) than bees from the "susceptible" genotypes. At the individual level, bees
      from the "resistant" genotypes performed significantly more instances of intense
      grooming (up to 4 fold), and a significantly higher number of mites were
      dislodged from the bees' bodies by intense grooming than by light grooming (up to
      7 fold) in all genotypes. The odds of mite removal were high and significant for
      all "resistant" genotypes when compared with the "susceptible" genotypes. The
      results of this study strongly suggest that grooming behavior and the intensity
      with which bees perform it, is an important component in the resistance of some
      honey bee genotypes to the growth of varroa mite populations. The implications of
      these results are discussed.

PMID- 22465571
TI  - QM/MM investigation on the catalytic mechanism of Bacteroides thetaiotaomicron
      alpha-glucosidase BtGH97a.
AB  - Bacteroides thetaiotaomicron alpha-glucosidase BtGH97a is an inverting enzyme. In
      this paper, the hydrolysis mechanism of p-nitro-phenyl alpha-d-glucopyranoside
      (pNP-Glc) catalyzed by BtGH97a was firstly studied by using quantum
      mechanical/molecular mechanical (QM/MM) approach. Two possible reaction pathways
      were considered. In the first pathway, a water molecule deprotonated by a
      nucleophilic base (here E439 or E508) attacks firstly on the anomeric carbon of
      pNP-Glc, then a proton from an acid residue (E532) attacks on the glycosidic
      oxygen to finish the hydrolysis reaction (named as nucleophilic attack-first
      pathway). In the second pathway, the proton from E532 attacks firstly on the
      glycosidic oxygen, then the water deprotonated by the nucleophilic base attacks
      on the anomeric carbon of pNP-Glc (named as proton attack-first pathway). Our
      calculation results indicate that the nucleophilic attack-first pathway is
      favorable in energy, in which the nucleophilic attack process is the rate
      determining step with an energy barrier of 15.4kcal/mol in the case of residue
      E508 as nucleophilic base. In this rate-determining step, the deprotonation of
      water and the attack on the anomeric carbon are concerted. In the proton attack
      first pathway, the proton attack on the glycosidic oxygen is the rate-determining
      step, and the energy barrier is 24.1kcal/mol. We conclude that the hydrolysis
      mechanism would follow nucleophilic attack-first pathway.

PMID- 22465570
TI  - Modulating molecular chaperones improves sensory fiber recovery and mitochondrial
      function in diabetic peripheral neuropathy.
AB  - Quantification of intra-epidermal nerve fibers (iENFs) is an important approach
      to stage diabetic peripheral neuropathy (DPN) and is a promising clinical
      endpoint for identifying beneficial therapeutics. Mechanistically, diabetes
      decreases neuronal mitochondrial function and enhancing mitochondrial respiratory
      capacity may aid neuronal recovery from glucotoxic insults. We have proposed that
      modulating the activity and expression of heat shock proteins (Hsp) may be of
      benefit in treating DPN. KU-32 is a C-terminal Hsp90 inhibitor that improved
      thermal hypoalgesia in diabetic C57Bl/6 mice but it was not determined if this
      was associated with an increase in iENF density and mitochondrial function. After
      16 weeks of diabetes, Swiss Webster mice showed decreased electrophysiological
      and psychosensory responses and a >30% loss of iENFs. Treatment of the mice with
      ten weekly doses of 20mg/kg KU-32 significantly reversed pre-existing deficits in
      nerve conduction velocity and responses to mechanical and thermal stimuli. KU-32
      therapy significantly reversed the pre-existing loss of iENFs despite the
      identification of a sub-group of drug-treated diabetic mice that showed improved
      thermal sensitivity but no increase in iENF density. To determine if the improved
      clinical indices correlated with enhanced mitochondrial activity, sensory neurons
      were isolated and mitochondrial bioenergetics assessed ex vivo using
      extracellular flux technology. Diabetes decreased maximal respiratory capacity in
      sensory neurons and this deficit was improved following KU-32 treatment. In
      conclusion, KU-32 improved physiological and morphologic markers of degenerative
      neuropathy and drug efficacy may be related to enhanced mitochondrial
      bioenergetics in sensory neurons.

PMID- 22465572
TI  - Dual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating
      monooxygenase.
AB  - Aspergillus fumigatus siderophore A (Af SidA) is a flavin-dependent monooxygenase
      that catalyzes the hydroxylation of ornithine, producing N(5)-hydroxyornithine.
      This is the first step in the biosynthesis of hydroxamate-containing siderophores
      in A. fumigatus. Af SidA is essential for virulence, validating this enzyme as a
      drug target. Af SidA can accept reducing equivalents from either NADPH or NADH
      and displays similar kinetic parameters when using either coenzyme. When the
      enzyme is reduced with NADPH and reacted with molecular oxygen, a C4a
      hydroperoxyflavin intermediate is observed. When the enzyme is reduced with NADH,
      the intermediate is 2-fold less stable. Steady-state kinetic isotope effect
      values of 3 and 2 were determined for NADPH and NADH, respectively. The
      difference in the isotope effect values is due to differences in the rate of
      flavin reduction by these coenzymes. A difference in the binding mode between
      these coenzymes was observed by monitoring flavin fluorescence. Limited
      proteolysis studies show that NADP(+), and not NAD(+), protects Af SidA from
      proteolysis, suggesting that it induces conformational changes upon binding.
      Together, these results are consistent with NADPH having a role in flavin
      reduction and in the modulation of conformational changes, which positions
      NADP(+) to also play a role in stabilization of the C4a-hydroperoxyflavin.

PMID- 22465573
TI  - A comparative study of the cytotoxicity and corrosion resistance of nickel
      titanium and titanium-niobium shape memory alloys.
AB  - Nickel-titanium (NiTi) shape memory alloys (SMAs) are commonly used in a range of
      biomedical applications. However, concerns exist regarding their use in certain
      biomedical scenarios due to the known toxicity of Ni and conflicting reports of
      NiTi corrosion resistance, particularly under dynamic loading. Titanium-niobium
      (TiNb) SMAs have recently been proposed as an alternative to NiTi SMAs due to the
      biocompatibility of both constituents, the ability of both Ti and Nb to form
      protective surface oxides, and their superior workability. However, several
      properties critical to the use of TiNb SMAs in biomedical applications have not
      been systematically explored in comparison with NiTi SMAs. These properties
      include cytocompatibility, corrosion resistance, and alterations in alloy surface
      composition in response to prolonged exposure to physiological solutions.
      Therefore, the goal of the present work was to comparatively investigate these
      aspects of NiTi (49.2 at.% Ti) and TiNb (26 at.% Nb) SMAs. The results from the
      current studies indicate that TiNb SMAs are less cytotoxic than NiTi SMAs, at
      least under static culture conditions. This increased TiNb cytocompatibility was
      correlated with reduced ion release as well as with increased corrosion
      resistance according to potentio-dynamic tests. Measurements of the surface
      composition of samples exposed to cell culture medium further supported the
      reduced ion release observed from TiNb relative to NiTi SMAs. Alloy composition
      depth profiles also suggested the formation of calcium phosphate deposits within
      the surface oxide layers of medium-exposed NiTi but not of TiNb. Collectively,
      the present results indicate that TiNb SMAs may be promising alternatives to NiTi
      for certain biomedical applications.

PMID- 22465574
TI  - Preparation of uniaxial multichannel silk fibroin scaffolds for guiding primary
      neurons.
AB  - Physical guidance cues have been exploited to stimulate neuron adhesion and
      neurite outgrowth. In the present study, three-dimensional (3-D) silk fibroin
      scaffolds with uniaxial multichannels (42-142 MUm in diameter) were prepared by a
      directional temperature field freezing technique, followed by lyophilization. By
      varying the initial silk fibroin concentration, the chemical potential and
      quantity of free water around cylindrical ice crystals could be controlled to
      control the cross-section morphology of the scaffold channels. Aligned ridges
      also formed on the inner surface of the multichannels in parallel to the
      direction of the channels. In vitro, primary hippocampal neurons were seeded in
      these 3-D silk fibroin scaffolds with uniaxial multichannels of ~120 MUm in
      diameter. The morphology of the neurons was multipolar and alignment along the
      scaffold channels was observed. Cell-cell networks and cell-matrix interactions
      established by newly formed axons were observed after 7 days in culture. These
      neurons expressed beta-III-tubulin, nerve filament and microtubule-associated
      protein, while glial fibrillary acidic protein immunofluorescence was barely
      above background. The ridges on the inner surface of the channels played a
      critical role in the adhesion and extension of neurons by providing continuous
      contact guidance. These new 3-D silk scaffolds with uniaxial multichannels
      provided a favorable microenvironment for the development of hippocampal neurons
      by guiding axonal elongation and cell migration.

PMID- 22465576
TI  - Variability in the nanoscale deformation of hydroxyapatite during compressive
      loading in bovine bone.
AB  - High-energy synchrotron X-ray diffraction is used to study in situ elastic
      strains in hydroxyapatite (HAP) for bovine femur cortical bone subjected to
      uniaxial compressive loading. Load-unload tests at room temperature (27 degrees
      C) and body temperature (37 degrees C) show that the load transfer to the stiff
      nanosized HAP platelets from the surrounding compliant protein matrix does not
      vary significantly (p<0.05) with temperature. This emphasizes that the stiffness
      of bone is controlled by the stiffness of the HAP phase, which remains unaffected
      by this change in temperature. Both the extent of hysteresis and the residual
      value of internal strains developed in HAP during load-unload cycling from 0 to 
      100 MPa increase significantly (p<0.05) with the number of loading cycles,
      indicative of strain energy dissipation and accumulation of permanent
      deformation. Monotonic loading tests, conducted at body temperature to determine
      the spatial variation of properties within the femur, illustrate that the HAP
      phase carries lower strain (and thus stresses) at the anterio-medial aspect of
      the femur than at the anterio-lateral aspect. This is correlated to higher HAP
      volume fractions in the former location (p<0.05). The Young's modulus of the bone
      is also found to correlate with the HAP volume fraction and porosity (p<0.05).
      Finally, samples with a primarily plexiform microstructure are found to be
      stiffer than those with a primarily Haversian microstructure (p<0.05).

PMID- 22465575
TI  - Controlled heparin conjugation on electrospun poly(epsilon-caprolactone)/gelatin
      fibers for morphology-dependent protein delivery and enhanced cellular affinity.
AB  - Electrospun fibrous scaffolds have now been shown to possess great potential for
      tissue engineering applications, owing to their unique mimicry of natural
      extracellular matrix structure. In this study, poly(epsilon-caprolactone) and
      gelatin were electrospun to fabricate tissue-engineered scaffolds with three
      different fiber morphologies (1.0 MUm, 3.0 MUm and co-electrospun containing both
      1.0 and 3.0 MUm diameter fibers). Subsequently, these scaffolds were conjugated
      with heparin to immobilize a bioactive molecule by electrostatic interactions.
      This study determined the quantity of heparin conjugation on the scaffolds and
      that the crosslinking time and the fiber morphologies govern the extent of
      heparin conjugation on the fibers. In order to evaluate the release capacity of
      the heparin-conjugated scaffolds, lysozyme was used as a model protein for
      conjugation. The heparin-conjugated scaffolds provided high loading efficiency
      and cumulative release of lysozyme with a relatively linear relationship. In
      addition, the release kinetics was significantly dependent on heparin conjugation
      and fiber morphology. This fundamental investigation into how fiber morphology
      and crosslinking protocols can affect the heparin binding ability of electrospun
      fibers is crucial for predicting the delivery of many different types of
      bioactive molecules from an electrospun scaffold for tissue engineering
      applications.

PMID- 22465578
TI  - Clinical efficacy of riboflavin and ultraviolet light inactivated fresh frozen
      plasma evaluated with INR-quantification.
AB  - Treatment of blood products by riboflavin and ultraviolet (UV) light prevents of
      white blood cell (WBC) replication and inactivates of pathogens. The aim of this
      study was to determine the effects of the inactivation by riboflavin and UV light
      upon plasma clinical performance, based on effect on the pretransfusion
      international normalized ratio (INR). A prospective, controlled randomized study
      included 60 patients who received transfusion of plasma on the Clinic for
      hematology of Clinical Centre in Nis. Experimental group (EG; 30 patients) was
      treated with Mirasol-inactivated fresh frozen plasma (FFP) and control group (CG;
      30 patients) was transfused with noninactivated FFP. Besides pretransfusion vs.
      posttransfusion INR, the improvement in INR patient's plasma level per one FFP
      unit transfused was evaluated. Total of 68 units of FFP were transfused to
      patients of CG (2.24+/-0.83 units per patient). Patients of EG received 84 units
      of Mirasol-inactivated plasma (i.e. 2.80+/-1.19 units per patient). There was
      significant increase in number of FFP transfusions that normalized coagulation
      parameters in EG compared to CG (p=0.039). Also, there was a significant
      improvement of INR after every FFP unit application (p=0.046). We found a linear
      relationship between pretransfusion INR and improvement of INR (r=0.97; p<0.001).
      Plasma treated with riboflavin and UV light retains hemostatic competence and can
      be used efficiently in the therapy of congenital or acquired coagulopathies, but
      in larger quantity as compared to noninactivated FFP volume.

PMID- 22465577
TI  - Spatial tuning of negative and positive Poisson's ratio in a multi-layer
      scaffold.
AB  - While elastic modulus is tunable in tissue engineering scaffolds, it is
      substantially more challenging to tune the Poisson's ratio of scaffolds. In
      certain biological applications, scaffolds with a tunable Poisson's ratio may be
      more suitable for emulating the behavior of native tissue mechanics. Here, we
      design and fabricate a scaffold, which exhibits simultaneous negative and
      positive Poisson's ratio behavior. Custom-made digital micro-mirror device
      stereolithography was used to fabricate single- and multiple-layer scaffolds
      using polyethylene glycol-based biomaterial. These scaffolds are composed of pore
      structures having special geometries, and deformation mechanisms, which can be
      tuned to exhibit both negative Poisson's ratio (NPR) and positive Poisson's ratio
      (PPR) behavior in a side-to-side or top-to-bottom configuration. Strain
      measurement results demonstrate that analytical deformation models and
      simulations accurately predict the Poisson's ratios of both the NPR and PPR
      regions. This hybrid Poisson's ratio property can be imparted to any photocurable
      material, and potentially be applicable in a variety of biomedical applications.

PMID- 22465579
TI  - An unusual presentation of lymphoma: chylotamponade.
AB  - Chylopericardium is an uncommon but potentially life-threatening clinic entity.
      Here we reported a case with chylopericardium causing tamponade and shock as an
      unusual presentation of lymphoma. The patient was managed by immediate
      pericardiocentesis. Further analysis of the pericardial fluid revealed immature T
      cells compatible with precursor T-lymphoblastic lymphoma.

PMID- 22465580
TI  - The effect of different trophic modes on lipid accumulation of Scenedesmus
      quadricauda.
AB  - In this study, the effects of different carbon sources on cell growth and lipid
      accumulation of Scenedesmus quadricauda were investigated. Results showed that S.
      quadricauda could grow on photoautotrophic, heterotrophic and mixotrophic modes.
      The lipid yield of S. quadricauda was much lower in the culture containing
      NaHCO(3) as only carbon source, while CO(2) and glucose concentration
      significantly influenced cell yield and lipid accumulation in photoautotrophic
      and heterotrophic culture, respectively. Furthermore, lipid content of S.
      quadricauda in mixotrophic culture (33.1% of cell dry weight) was much higher
      than that in photoautotrophic and heterotrophic cultivation (14-28%). Therefore,
      upon comparing these three trophic modes, present results revealed mixotrophy was
      the optimal culture method for S. quadricauda to produce lipid. Besides, it was a
      feasible and promising strategy to culture S. quadricauda using starch wastewater
      as raw material, which could reduce chemical oxygen demand (COD) of wastewater
      and the cost of biodiesel production.

PMID- 22465581
TI  - Economical production of poly(gamma-glutamic acid) using untreated cane molasses
      and monosodium glutamate waste liquor by Bacillus subtilis NX-2.
AB  - The production of poly(gamma-glutamic acid) by Bacillus subtilis NX-2 from cane
      molasses and monosodium glutamate waste liquor (MGWL) was studied for the first
      time in this work. When batch fermentation was carried out with untreated
      molasses, 33.6+/-0.37 g L(-1) PGA was obtained with a productivity of 0.46+/
      0.006 g L(-1) h(-1). In order to minimize the substrate inhibition, fed-batch
      fermentation was performed with untreated or hydrolyzed molasses in 7.5 L
      bioreactor, giving 50.2+/-0.53 and 51.1+/-0.51 g L(-1) of PGA at 96 h,
      respectively. Further studies were carried out by using MGWL as another carbon
      source, resulting in a PGA concentration of 52.1+/-0.52 g L(-1) with a
      productivity of 0.54+/-0.003 g L(-1) h(-1). These results suggest that the low
      cost cane molasses and MGWL can be used for the environmental-friendly and
      economical production of PGA by B. subtilis NX-2.

PMID- 22465582
TI  - The effect of rehabilitation in a comprehensive inpatient rehabilitation unit on
      mobility outcome after dysvascular lower extremity amputation.
AB  - OBJECTIVES: To (1) compare the total volume of rehabilitation therapy for
      patients ever attending a comprehensive inpatient rehabilitation unit (CIRU)
      versus never during the 12 months after amputation; (2) determine whether
      rehabilitation in a CIRU at any time in the first year after amputation results
      in greater mobility success compared with other types of rehabilitation
      environments of care; and (3) determine for those patients treated in a CIRU,
      which specific patient characteristics were associated with improved mobility
      outcome. DESIGN: Prospective cohort study. SETTING: Two Veterans Affairs medical
      centers. PARTICIPANTS: Patients (N=199) with peripheral vascular disease or
      diabetes undergoing a first unilateral major amputation were screened for
      participation between September 2005 and December 2008. Among these, 113 (57%)
      met study criteria; of these, 72 (64%) participated. INTERVENTION: Ever attending
      a CIRU versus never attending a CIRU in first 12 months after amputation. MAIN
      OUTCOME MEASURES: Number of rehabilitation therapy visits, Locomotor Capability
      Index scores, and mobility success. RESULTS: The mean number of all therapy
      visits for patients ever attending a CIRU was significantly greater than that for
      those never attending over a 12-month period (48.6 vs 22.6; P=.001). Mean total
      time per any rehabilitation visit was .83+/-.27 hours for those ever attending
      and .60+/-.20 hours for those never attending (P<.001). Patients who ever were
      treated in a CIRU were 17% more likely to achieve mobility success than those who
      were not, controlling for amputation level, major depressive episode, alcohol
      use, social support, total number of rehabilitation visits, and hospital site
      (risk difference=.17; 95% confidence interval, .09-.25; P<.001). CONCLUSIONS:
      Rehabilitation in a CIRU resulted in improved mobility success for veterans
      undergoing major lower extremity amputation secondary to peripheral vascular
      disease or diabetes. Among those admitted to a CIRU, younger patients with
      greater social support, healthy weight, and without chronic obstructive pulmonary
      disease had the greatest probability of mobility success.

PMID- 22465583
TI  - Electromyogram-lengthening velocity relation in plantar flexors during stance
      phase of gait in patients with hypertonia after acquired brain injury.
AB  - OBJECTIVE: To examine the velocity-dependent change in medial gastrocnemius (MG)
      activity during the stance phase of gait in patients with moderate to severe
      resting hypertonia after stroke or traumatic brain injury (TBI). DESIGN: Cohort
      study. SETTING: Motion analysis laboratory in a tertiary-care rehabilitation
      hospital. PARTICIPANTS: Convenience sample of patients with chronic TBI and
      stroke (n=11 each), and age- and sex-matched healthy controls (n=22).
      INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Frequency and gain
      (steepness) of positive (>0) and significant positive (>0 and goodness of fit
      P<=.05) electromyogram-lengthening velocity (EMG-LV) linear regression slope in
      MG during the stance phase of gait. RESULTS: Positive and significant positive
      slopes were found significantly more often on the more affected (MA) than less
      affected (LA) side in patients with TBI but not stroke. Both the frequencies of
      positive and significant positive slopes on the MA side in patients with TBI were
      also significantly higher than in controls. However, neither the gain of positive
      nor significant positive EMG-LV slope was different between the MA and LA sides
      or in comparison with controls. Positive slope parameters were not related to
      Ashworth score on the MA side. CONCLUSIONS: The frequency and gain of positive
      EMG-lengthening slope did not effectively differentiate patients from controls,
      nor were they related to the resting muscle hypertonia. Motor output during MG
      lengthening in the stance phase of gait is apparently not exaggerated or related
      to resting hypertonia in patients with chronic TBI and stroke. Thus, changes in
      gait during stance cannot be ascribed to increased stretch reflex activity in MG
      muscle after acquired brain injury.

PMID- 22465584
TI  - Predictors of changes in sentimental and sexual life after traumatic spinal cord
      injury.
AB  - OBJECTIVE: To investigate changes and identify predictors in interpersonal
      functioning and sexual life after traumatic spinal cord injury (SCI). DESIGN:
      Prospective, multicenter, follow-up observational study. SETTING: Subjects at
      home, interviewed by phone during a 6-month period, 3.8 mean years after
      discharge from 24 centers participating in a previous epidemiologic prospective
      survey. PARTICIPANTS: Subjects (N=403) with traumatic SCI. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES:  DEPENDENT VARIABLES: satisfaction with
      sentimental life and satisfaction with sexual life compared with before the
      injury. INDEPENDENT VARIABLES: demographic (age, sex, marital status, vocational
      status), SCI related (severity, level, bowel/bladder continence), car-driving
      ability, perceived quality of life (QoL), and impact of sentimental life, social
      integration, and vocational status on QoL. RESULTS: Satisfaction with sentimental
      life was reportedly increased or the same as before SCI in 69% of the sample, but
      satisfaction with sexual life in only 31%. Lesser satisfaction with sexual life
      was reported by men than women (P=.002) and by married people than singles
      (P<.001). Significant predictors of sentimental life were perceived QoL and
      preserved driving ability (R(2)=.195). Bladder continence was positively
      associated with a better satisfaction with sexual life (R(2)=.368). Bowel
      continence did not remain a significant predictor of satisfaction with sexual
      life in multivariate analysis. CONCLUSIONS: The challenge of a comprehensive
      rehabilitation of SCI, addressing the recovery of well-being including a
      satisfying sentimental and sexual life, requires identifying new issues that
      should be considered in up-to-date rehabilitation programs. The results indicate
      associations between driving ability and a better satisfaction with sentimental
      life. Further investigations are needed to explore whether the relationship is
      causative.

PMID- 22465585
TI  - Kinematic determinants of anterior knee pain in cerebral palsy: a case-control
      study.
AB  - OBJECTIVE: To quantify the role patellofemoral and tibiofemoral kinematics may
      play in development of anterior knee pain (AKP) in individuals with cerebral
      palsy (CP). DESIGN: Case-control. SETTING: Clinical research center.
      PARTICIPANTS: Knees from individuals with diagnosed CP (n=20) and control knees
      (n=40) were evaluated. Controls were matched for sex and age based on the group
      average. Matching by height and weight was a secondary priority. Subjects in the
      control cohort were asymptomatic with no history of lower leg abnormalities,
      surgery, or major injury. Only individuals who were physically capable of
      sustaining slow, cyclic knee flexion-extension for 2.5 minutes and had no
      contraindications to magnetic resonance imaging were enrolled. Both groups were
      samples of convenience. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Three-dimensional patellofemoral and tibiofemoral joint kinematics, acquired
      during active leg extension, under volitional control. RESULTS: Participants with
      CP and AKP (n=8) demonstrated significantly greater patellofemoral extension,
      valgus rotation, and superior and posterior displacement relative to controls and
      to the subgroup of participants with CP and no AKP (n=12). Patellofemoral
      extension discriminated AKP in individuals with CP with 100% accuracy.
      CONCLUSIONS: In quantifying the 3-dimensional, in vivo knee joint kinematics
      during a volitional extension task, kinematic markers that discriminate AKP in
      individuals with CP were identified. This provides an ability to predict which
      individuals with CP are most likely to develop AKP and could enable aggressive
      conservative treatment, aimed at reducing patella alta and excessive
      patellofemoral extension, to be prescribed before considering surgical options.
      The current findings will likely lead to improved clinical diagnostics and
      interventions for individuals with CP, with the ultimate goal of helping
      maintain, if not improve, functional mobility throughout the lifespan.

PMID- 22465586
TI  - New insight into the genomic structure of dog T cell receptor beta (TRB) locus
      inferred from expression analysis.
AB  - Here is an updated report on the genomic organization of T cell receptor beta
      (TRB) locus in the domestic dog (Canis lupus familiaris) as inferred from
      comparative genomics and expression analysis. The most interesting results we
      found were a second TRBD-J-C cluster, which is absent from the reference genome
      sequence, and the annotation of two additional TRBV genes. In dogs, TRB locus
      consists of a library of 37 TRBV genes positioned at the 5' end of two in tandem
      aligned D-J-C gene clusters, each composed of a single TRBD, 6 TRBJ and one TRBC
      genes, followed by a single TRBV gene with an inverted transcriptional
      orientation. The TRB genes are distributed in less than 300kb, making the canine
      locus, one of the smaller mammalian TRB locus studied so far. The small size may
      be ascribed to reduced gene duplication occurrences and a lower density of total
      interspersed repeats compared to humans and mice. Despite the low TRBV gene
      content, a large and diversified beta chain repertoire is displayed in the dog
      peripheral blood. A full usage of TRBV and TRBJ genes, including pseudogenes, and
      a high level of allelic polymorphism contribute to generate diversity. Finally,
      this study suggests that the overall TRB locus organization is evolutionarily
      conserved supporting the dog as a highly suited model system for immune
      development and diseases.

PMID- 22465587
TI  - Perioperative mortality following above-knee amputations indicated for bone and
      soft tissue tumours.
AB  - Whilst there are numerous studies investigating perioperative mortality of
      amputations performed for peripheral vascular disease, there are few studies
      exploring this in oncology patients. The authors have reviewed their experience
      in oncology patients who had had an above-knee amputation (AKA), investigating
      the incidence of reported thromboembolic events, and death. METHOD: Retrospective
      review of data stored on a prospective database. RESULTS: 484 patients were
      identified that had had an above-knee amputation between 1980 and 2011. The most
      common diagnosis leading to amputation was osteosarcoma (45%) followed by
      chondrosarcoma (6%). The majority of patients (301) underwent their above-knee
      amputation as a primary procedure (62%). There were two inpatient deaths soon
      after the above-knee amputation (mortality 0.4%) and a further two deaths within
      30 days of the procedure (30 day mortality 1%). Only two deaths were directly
      related to the procedure and were due to a pulmonary embolism. The incidence of
      non-fatal, clinically evident thromboembolic events was 0.6% in the defined
      perioperative period of 30 days. The one-year survival was 79% and the five-year
      survival was 52%. Patients who had an amputation due to failure of reconstruction
      were found to have a better survival. CONCLUSION: Above-knee amputations are
      performed mainly for vascular indications but also for bone or soft tissue
      tumours of the lower limbs; representing two completely different patient groups
      reflected by the perioperative risk, significantly lower in oncology patients
      (<1% vs 8-23%). Although a high risk group there is no consensus regarding
      thromboprophylaxis due to the increased risk of bleeding. However, due to the low
      complication rates of modern methods of prophylaxis the authors propose routine
      prophylaxis for patients undergoing above-knee amputations if they are aged over
      60 or have other risk factors for thrombo-embolic disease.

PMID- 22465588
TI  - Lymph node ratio is an independent prognostic factor in patients with rectal
      cancer treated with preoperative chemoradiotherapy and curative resection.
AB  - PURPOSE: To evaluate the prognostic effect of lymph node ratio (LNR) in patients
      with locally advanced rectal cancer who were treated with curative resection
      after preoperative chemoradiotherapy (CRT). METHODS: Between October 2001 and
      December 2007, 519 patients who had undergone curative resection of primary
      rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were
      positive for lymph node (LN) metastasis and were divided into three groups
      according to the LNR (<= 0.15 [n=80], 0.16-0.3 [n=44], >0.3 [n=30]) to evaluate
      the prognostic effect on overall survival (OS) and disease-free survival (DFS).
      RESULTS: LNR (<= 0.15, 0.16-0.3, and >0.3) was significantly associated with 5
      year OS (90.3%, 75.1%, and 45.1%; p<0.001) and DFS (66.7%, 55.8%, and 21.9%;
      p<0.001) rates. In a multivariate analysis, LNR (<= 0.15, 0.16-0.3, and >0.3) was
      a significant independent prognostic factor for OS (hazard ratios [HRs], 1,
      3.609, and 8.197; p<0.001) and DFS (HRs, 1, 1.699, and 3.960; p<0.001). LNR had a
      prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in
      those with >= 12 harvested LNs (p<0.05). CONCLUSION: LNR was a significant
      independent prognostic predictor for OS and DFS in patients with locally advanced
      rectal cancer who were treated with curative resection after preoperative CRT.

PMID- 22465589
TI  - Occlusion of both caval veins by an endovascular occluder.
AB  - Minimally invasive surgery (MIS) for redo mitral/tricuspidal surgery is going to
      increase, offering good results for early and late mortality and morbidity. In a
      case of redo surgery through a right thoracotomy (RT), when tricuspid surgery is
      planned, the superior (SVC) and inferior caval veins (IVC) are usually isolated
      and snared in order to prevent air embolism and significant blood regurgitation.
      We describe our experience in eight redo patients, operated for combined
      mitral/tricuspid or isolated tricuspid surgery, where the endovascular occlusion
      of the SVC and IVC was obtained by means of an endovascular occluder (Equalizer).

PMID- 22465590
TI  - In vitro anti-prostate cancer and ex vivo antiangiogenic activity of Vernonia
      guineensis Benth. (Asteraceae) tuber extracts.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer is a major problem worldwide and
      affects most men above the age of forty-five. Vernonia guineensis Benth.
      (Asteraceae) root decoction is used in folk medicine in Cameroon to treat a
      number of ailments including prostate cancer. The aim of this study was to
      provide a preliminary validation of the use of Vernonia guineensis Benth.
      extracts to treat prostate cancer by evaluating the in vitro activity of its
      crude extracts and isolated molecules on prostate cancer cells lines and effect
      on angiogenesis which is essential for growth and metastases of prostate cancer.
      MATERIALS AND METHODS: Aqueous, dichloromethane and methanol extracts of Vernonia
      guineensis Benth. tubers were tested for activity against three prostate cancer
      cell lines (PC-3, DU-145 and AT3B-1). The dichloromethane extract was subjected
      to bioactivity guided fractionation. Anti-proliferation, clonogenic and
      antiangiogenic activity of the crude extracts and isolated compound were tested.
      The WST-1 assay was used for the anti-proliferation activity meanwhile the
      standard clonogenic test and the rat ring aorta assay were carried out to
      determine the clonogenic and antiangiogenic activity of tested products
      respectively. RESULTS: The aqueous and methanol extracts of Vernonia guineensis
      Benth. demonstrated weak activity against prostate cancer cell lines in vitro
      with IC(50)>100 MUg/mL. The dichloromethane extract was more potent with IC(50)
      of 56.233+/-3.630 MUg/ml and 67.316+/-2.452 MUg/ml against the DU-145 and PC-3
      cell lines respectively. Activity guided fractionation of this extract yielded a
      Pentaisovalerylsucrose (1) isolated for the first time from a natural source to
      the best of our knowledge. Compound 1 demonstrated in vitro activity against the
      human prostate cancer cell lines PC-3 and DU-145 with IC(50) of 5.701+/-0.142 MUM
      and 4.275+/-0.710 MUM, respectively. The IC(50) of the compound was 5.763+/-0.425
      MUM against AT3B-1, a rat prostate cancer cell line expressing P-glycoprotein
      which is linked to drug resistance in most metastatic cancers. Compared to
      compound 1, Paclitaxel and Docetaxel were active against AT3B-1 at 2.641+/-1.253
      MUM and 0.613+/-0.251 MUM. Paclitaxel showed IC(50) values of 0.004+/-0.002 MUM
      and 0.003+/-0.001 MUM against DU-145 and PC-3 prostate cancer cell lines
      respectively. Docetaxel showed IC(50) values of 0.002+/-0.001 MUM and 0.004+/
      0.001 MUM against DU-145 and PC-3 prostate cancer cell lines respectively.
      CONCLUSION: The in vitro anti-prostate cancer and the antiangiogenic activity of
      Vernonia guineensis Benth. extracts and isolated compound support the use of the
      tubers of this plant for the treatment of prostate cancer.

PMID- 22465591
TI  - Ethnobotanical survey and antibacterial activity of plants used in the Altiplane
      region of Mexico for the treatment of oral cavity infections.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The ethnobotanical survey conducted in this study
      showed 47 plant species used in the Altiplane region of Mexico for the treatment
      of dental diseases such as toothache, dental caries, periodontal disease and
      gingivitis. MATERIALS AND METHODS: Information was collected by performing
      interviews. The following data were recorded: name of the patients or herbalists
      with their age, sex; date and place of gathering information; pathology of
      persons interviewed; name of the drug (vernacular name); parts used (leaves,
      bark, fruits, seeds, aerial parts), mode of preparation and administration, and
      possible combinations. The inhibitory effects of the aqueous and ethanolic
      extracts of the medicinal plants detected during the survey the on the growth of
      Streptococcus mutans and Phrophyromonas gingivalis were determined using
      microdilution method. The minimum bactericidal concentrations (MBC) were
      determined from the wells of microplate with no visible bacterial growth.
      RESULTS: In total, tree places of the Altiplane region of Mexico were visited and
      five healers and 100 patients were questioned. 47 wild and cultivated species
      were recorded. The most frequent uses were to treat tooth pain, gum diseases, bad
      breath and cavities. Infusions were the most frequently prepared formulation.
      Other applied preparations mentioned with decreasing frequency were decocts,
      syrups, tinctures, direct application of the plant material without prior
      preparation and finally macerations. The ethanolic extracts of Haematoxylon
      brasiletto, Punica granatum, Iostephane heterophyla, Bursera simaruba, Cedrela
      odorata and Rhus standleyi (12.5-65.0 MUg/mL) as well as water extracts of
      Haematoxylon brasiletto, Punica granatum, Iostephane heterophyla, Amphipterygium
      adstringens, Argemone mexicana, Cedrela odorata, Eysenhardtia polystachya, Persea
      americana, Syzygium aromaticum, Cinnamomun zeylanicum, Cnidoscolus multilobus and
      Rhus standleyi (10.5-78.0 MUg/mL) showed the highest inhibitory effect against
      Streptococcus mutans and Porphyromonas gingivalis. CONCLUSIONS: Many plants are
      used in the Mexican traditional medicine to treat oral bacterial diseases by the
      healers or patients. Our study demonstrated that most of the medicinal plants
      showed an antibacterial effect in vitro, and justified at least in part their use
      in traditional medicine. These results encourage further investigations to
      extract and identify the active chemical compounds responsible for the
      antibacterial effect observed.

PMID- 22465593
TI  - Bioassay-guided fractionation of a thymol-deprived hydrophilic thyme extract and
      its antispasmodic effect.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from Thymus vulgaris L. and Thymus zygis
      L. are traditionally used for bronchitis, catarrhs of the respiratory tract and
      supportive treatment of pertussis. A potential spasmolytic effect is thought to
      be due to the presence of the monoterpenoid phenols thymol and carvacrol in the
      extract. Based on previous data the present investigation aimed to clarify if
      thymol-deprived thyme extracts (as been in use within German drug market) have
      antispasmodic activity. Additionally compounds responsible for this effect had to
      be identified. MATERIALS AND METHODS: Thyme fluid extract was subsequently
      fractionated by FCPC, LPLC, and HPLC and compounds isolated were identified by
      spectroscopic methods. Bioassay testing was done by quantification of
      antispasmodic activity in the preconstricted rat smooth muscle trachea model
      against papaverin as positive control. RESULTS: Thymol-deprived spissum extract
      (SE) had good antispasmodic activity (-37%, related to the maximum contraction).
      Bioassay-guided fractionation indicated that rosmarinic acid and apigenin do not
      contribute to this effect. Luteolin contributed significantly to the
      antispasmodic activity (-9%). CONCLUSIONS: Thyme extracts have antispasmodic
      activity, which is at least due to synergistic effects of phenolic volatile oil
      compounds and the flavone luteolin. Specifications of thyme-containing
      preparations should refer to this flavone in addition to focusing on the volatile
      phenols.

PMID- 22465592
TI  - Ethnopharmacology in overdrive: the remarkable anti-HIV activity of Artemisia
      annua.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua contains the well-known
      antimalarial compound artemisinin, which forms the backbone of the global malaria
      treatment regime. In African countries a tea infusion prepared from Artemisia
      annua has been used for the treatment of malaria only for the past 10-20 years.
      Several informal claims in Africa exist that the Artemisia annua tea infusions
      are also able to inhibit HIV. Since HIV is a relatively newly emerged disease,
      the claims, if substantiated, could provide a very good example of
      "ethnopharmacology in overdrive". The objective of this study was to provide
      quantitative scientific evidence that the Artemisia annua tea infusion exhibits
      anti-HIV activity through in vitro studies. A second objective was to determine
      if artemisinin plays a direct or indirect (synergistic) role in any observed
      activity. This was done by the inclusion of a chemically closely related species,
      Artemisia afra, known not to contain any artemisinin in our studies. MATERIALS
      AND METHODS: Validated cellular systems were used to test Artemisia annua tea
      samples for anti-HIV activity. Two independent tests with different formats (an
      infection format and a co-cultivation format) were used. Samples were also tested
      for cellular toxicity against the human cells used in the assays. RESULTS: The
      Artemisia annua tea infusion was found to be highly active with IC(50) values as
      low as 2.0 MUg/mL. Moreover we found that artemisinin was inactive at 25 MUg/mL
      and that a chemically related species Artemisia afra (not containing artemisinin)
      showed a similar level of activity. This indicates that the role of artemisinin,
      directly or indirectly (synergism), in the observed activity is rather limited.
      Additionally, no cellular toxicity was seen for the tea infusion at the highest
      concentrations tested. CONCLUSION: This study provides the first in vitro
      evidence of anti-HIV activity of the Artemisia annua tea infusion. We also report
      for the first time on the anti-HIV activity of Artemisia afra although this was
      not an objective of this study. These results open the way to identify new active
      pharmaceutical ingredients in Artemisia annua and thereby potentially reduce the
      cost for the production of the important antimalarial compound artemisinin.

PMID- 22465594
TI  - Stress, glucocorticoids and absences in a genetic epilepsy model.
AB  - Although stress can alter the susceptibility of patients and animal models to
      convulsive epilepsy, little is known about the role of stress and glucocorticoid
      hormones in absence epilepsy. We measured the basal and acute stress-induced
      (foot-shocks: FS) concentrations of corticosterone in WAG/Rij rats, non-epileptic
      inbred ACI rats and outbred Wistar rats. The WAG/Rij strain is a genetic model
      for absence epilepsy and comorbidity for depression, which originates from the
      population of Wistar rats and, therefore, shares their genetic background. In a
      separate experiment, WAG/Rij rats were exposed to FS on three consecutive days.
      Electroencephalograms (EEGs) were recorded before and after FS, and the number of
      absence seizures (spike-wave-discharges, SWDs) was quantified. Both WAG/Rij rats
      and ACI rats exhibited elevated basal levels of corticosterone and a rapid
      corticosterone increase in response to acute stress. The WAG/Rij rats also
      displayed the most rapid normalization of corticosterone during the recovery
      phase compared to that of ACI and Wistar rats. FS had a biphasic effect on SWDs;
      an initial suppression was followed by an aggravation of the SWDs. By the third
      day, this aggravation of seizures was present in the hour preceding FS. This
      increase in SWDs may arise from anticipatory stress about the upcoming FS.
      Together, these results suggest that the distinct secretion profile of
      corticosterone found in WAG/Rij rats may contribute to the severity of the
      epileptic phenotype. Although the acute stressor results in an initial
      suppression of SWDs followed by an increase in SWDs, stress prior to a
      predictable negative event aggravates absences.

PMID- 22465595
TI  - Superficial mastoid fascia as an accessible donor for various augmentations in
      Asian rhinoplasty.
AB  - This study was designed to assess the anatomic characteristics and clinical
      versatility of superficial mastoid fascia as a soft-tissue donor for augmentation
      in Asian rhinoplasty. Dissections were performed on four fresh cadavers (eight
      ears) for histologic study. A 3*10 mm2-sized full layer of skin and underlying
      soft tissue was harvested from the postauricular area, transversely and
      longitudinally (cephalic and caudal directions), 5 mm apart from the midpoint of
      the auriculocephalic sulcus. The average fascial thickness and nerve distribution
      were assessed using digital microscopic images after haematoxylin and eosin (H&E)
      staining. In the histologic study, the average measured thickness of the
      superficial mastoid fascia was between 3.8 and 4.5 mm in various directions.
      Clinically, 33 subjects who underwent rhinoplasty using superficial mastoid
      fascia were assessed prospectively. When soft tissue was needed in various types
      of augmentations, a longitudinal incision was made on the posterior
      auriculocephalic sulcus and the maximum thickness of superficial mastoid fascia
      was harvested. The sizes of the superficial mastoid fascia used in the 33
      subjects ranged from 0.4*2.5 cm2 to 1.2*4.2 cm2. The superficial mastoid fascia
      was grafted regionally for the nasion, tip and nasal dorsum. In two cases,
      hypertrophic scars developed at the donor site. Four subjects experienced
      transient dysaesthesia and hypoaesthesia at the donor area postoperatively.
      Superficial mastoid fascia may be a useful resource in rhinoplasty as a donor for
      various types of augmentations, allowing easy access without prominent scarring
      or permanent sensory nerve damage when a low-to-moderate volume of soft tissue is
      required.

PMID- 22465596
TI  - Butterfly reconstruction of the anterior scalp hairline using bilaterally
      apposing STA island flaps.
AB  - Traditional methods of reconstruction of the hair-bearing scalp can provide
      incorrect directional hair growth and may require secondary procedures to
      complete. We present a case of reconstruction of the anterior hairline after
      tumour resection in an infant. Lessons learned from the case have led to a novel
      method for a single stage reconstruction of the anterior hairline using pedicled
      superficial artery flaps.

PMID- 22465597
TI  - Long term functional results from major limb replantations.
AB  - Replantation is now firmly established as a viable treatment option in traumatic
      limb amputation, yet there are few long-term studies describing the functional
      outcome of these cases. The purpose of the present study was to evaluate long
      term results in a population of such patients to determine overall success and
      patient satisfaction. Since 1981, twenty macro-replants involving nineteen
      patients have been performed in our unit. All patients were reviewed by means of
      case note analysis, patient questionnaire, and follow-up clinical evaluation for
      functional outcome using the Tamai scoring system. Acute limb salvage was
      successful in 18/20 (90%) cases. One patient is still undergoing secondary
      reconstructive surgery and was unable to be assessed for final outcome leaving 17
      replanted limbs that underwent full functional assessment. Overall functional
      results were good in 7/17 (41%) limbs, fair in 7/17 (41%) and poor in 3/17 (18%).
      The majority of patients (12/17) claimed to be highly or well satisfied with
      their outcome and eleven have returned to work since their injury. The current
      study of major limb replantation demonstrates favorable or acceptable long term
      functional outcomes in the majority of cases. High patient satisfaction rates
      even where results were poor emphasise the positive psychological impact of
      successful replantation.

PMID- 22465598
TI  - N-Succinyl-chitosan nanoparticles induced mitochondria-dependent apoptosis in
      K562.
AB  - N-Succinyl-chitosan nanoparticles (NSCNP) are synthetical nanoparticles derived
      from chitosan. In our previous study, we demonstrated that NSCNP could induce
      apoptosis in K562 cells, which were evidenced by decreasing cell zeta potential,
      disrupting the mitochondrial membrane potential, increasing ROS generation and
      Ca2+ concentration. Here, by western blot we revealed that apoptosis induced by
      NSCNP was associated with accumulation of cytochrome c in cytosol and elevating
      expression of apoptosis-promoted protein Bax while depressing expression of
      apoptosis-restrained protein Bcl-2 in time- and dose-dependence. Cell cycle
      blocking in G2/M phase was evidenced by kinetic cell cycle analysis. The
      activations of caspase-9 and 3, not caspase-8 were observed by fluorescent and
      colorimetric assays. Our data suggested that the apoptotic signals triggered by
      NSCNP were mediated mainly through the intrinsic mitochondria-dependent pathway.

PMID- 22465599
TI  - Modeling microbial communities: current, developing, and future technologies for
      predicting microbial community interaction.
AB  - Never has there been a greater opportunity for investigating microbial
      communities. Not only are the profound effects of microbial ecology on every
      aspect of Earth's geochemical cycles beginning to be understood, but also the
      analytical and computational tools for investigating microbial Earth are
      undergoing a rapid revolution. This environmental microbial interactome, the
      system of interactions between the microbiome and the environment, has shaped the
      planet's past and will undoubtedly continue to do so in the future. We review
      recent approaches for modeling microbial community structures and the
      interactions of microbial populations with their environments. Different modeling
      approaches consider the environmental microbial interactome from different
      aspects, and each provides insights to different facets of microbial ecology. We
      discuss the challenges and opportunities for the future of microbial modeling and
      describe recent advances in microbial community modeling that are extending
      current descriptive technologies into a predictive science.

PMID- 22465600
TI  - Fractionation of sulphite spent liquor for biochemical processing using ion
      exchange resins.
AB  - Sulphite spent liquor (SSL) is a side product from acidic sulphite pulping of
      wood, which organic counterpart is composed mainly by lignosulphonates (LS) and
      sugars. The last are a prominent substrate for the bioprocessing although a
      previous purification step is necessary to eliminate microbial inhibitors. In
      this study a fractionation of hardwood SSL (HSSL) has been accomplished employing
      ion exchange resins in order to separate sugars fraction from concomitant
      inhibitors: LS, acetic acid, furan derivatives, phenolics, acetic acid and excess
      of inorganic salts. The fractionation of HSSL has been carried out using two
      fixed-bed ion exchangers in series (cationic+anionic). The first cation exchange
      column packed with Dowex 50WX2 resin was able to eliminate free cations and
      partially separate sugars from high molecular weight LS and furan derivatives.
      The second anion exchange column packed with Amberlite IRA-96 sorbed remaining
      LS, phenolics and acetic acid. Overall, the series arrangement under
      investigation has removed 99.99% of Mg(2+), 99.0% of Ca(2+), 99.6% of LS, and
      100% of acetic acid, whereas the yield of recovered sugars was at least 72% of
      their total amount in HSSL.

PMID- 22465601
TI  - Chip-based amperometric enzyme sensor system for monitoring of bioprocesses by
      flow-injection analysis.
AB  - A microfluidic chip integrating amperometric enzyme sensors for the detection of
      glucose, glutamate and glutamine in cell-culture fermentation processes has been
      developed. The enzymes glucose oxidase, glutamate oxidase and glutaminase were
      immobilized by means of cross-linking with glutaraldehyde on platinum thin-film
      electrodes integrated within a microfluidic channel. The biosensor chip was
      coupled to a flow-injection analysis system for electrochemical characterization
      of the sensors. The sensors have been characterized in terms of sensitivity,
      linear working range and detection limit. The sensitivity evaluated from the
      respective peak areas was 1.47, 3.68 and 0.28 MUAs/mM for the glucose, glutamate
      and glutamine sensor, respectively. The calibration curves were linear up to a
      concentration of 20 mM glucose and glutamine and up to 10 mM for glutamate. The
      lower detection limit amounted to be 0.05 mM for the glucose and glutamate
      sensor, respectively, and 0.1 mM for the glutamine sensor. Experiments in cell
      culture medium have demonstrated a good correlation between the glutamate,
      glutamine and glucose concentrations measured with the chip-based biosensors in a
      differential-mode and the commercially available instrumentation. The obtained
      results demonstrate the feasibility of the realized microfluidic biosensor chip
      for monitoring of bioprocesses.

PMID- 22465602
TI  - Pharmacokinetics of bisphenol A in serum and adipose tissue following intravenous
      administration to adult female CD-1 mice.
AB  - Bisphenol A (BPA) is an important industrial chemical used as the monomer for
      polycarbonate plastic and in epoxy resins for use in food can liners. Worldwide
      biomonitoring studies consistently find high prevalence of BPA conjugates in
      urine consistent with pervasive exposure at levels typically below 1 MUg/kg
      bw/day. The current study used LC/MS/MS to measure serum pharmacokinetics of
      unconjugated (active) and conjugated (inactive) BPA in adult female CD-1 mice
      following intravenous (IV) injection, which produces higher serum levels by
      circumventing the processes of absorption from the GI tract and presystemic
      metabolism that occur after oral administration. Deuterated BPA (100 MUg/kg bw)
      was used to avoid interference by background contamination from trace amounts of
      native BPA. Additionally, the pharmacokinetics of unconjugated BPA were
      determined in adipose tissue, a proposed site of action and "depot" for BPA.
      After IV injection, unconjugated BPA rapidly distributed out of the circulation
      (t(1/2)=0.2 h) and terminal elimination also proceeded rapidly (t(1/2)=0.8 h).
      Consistent with the degree of aqueous solubility, lipid/water solubility ratio,
      and partitioning from blood into adipose tissue in vivo, the levels of
      unconjugated BPA in mouse adipose tissue rapidly reached a maximal level (0.25 h)
      that did not exceed the serum maximum at the initial sampling time (0.08 h).
      Terminal elimination of unconjugated BPA from adipose tissue (t(1/2)=7.0 h) was
      similar to that for conjugated BPA in serum (t(1/2)=6.6 h) and <0.01% of the
      administered dose remained in adipose tissue after 24 h. These plasma and tissue
      kinetics are consistent with rapid equilibria and underscore the non-persistent
      nature of BPA, particularly when compared with slowly metabolized lipophilic
      organic pollutants like halogenated dibenzodioxins.

PMID- 22465604
TI  - P-wave terminal force and atrial fibrillation: a lesson learned from old masters.

PMID- 22465603
TI  - Inhibition of Rho-kinase ameliorates myocardial remodeling and fibrosis in
      pressure overload and myocardial infarction: role of TGF-beta1-TAK1.
AB  - Inhibition of Rho-kinase displays vasodilation property although its effect on
      cardiac remodeling in heart against pressure overload and ischemia has not been
      fully elucidated. The present study was designed to examine the effect of
      fasudil, a Rho-kinase (ROCK) inhibitor, on myocardial remodeling and underlying
      mechanisms in pressure overload and myocardial infarction (MI) mice. Pressure
      overload was produced by constriction of the transverse aorta (TAC) for 3 weeks.
      Left ventricular (LV) geometry, cardiac hypertrophy, fibrosis, and remodeling
      were evaluated by transthoracic echocardiography and cardiac histology.
      Expressions of the hypertrophic and profibrotic markers were analyzed in TAC and
      MI mice with or without fasudil treatment. LV cavity dilatation and dysfunction
      evaluated by echocardiography were significantly suppressed in the fasudil
      treated MI group compared with the MI group (P<0.05); however, there were no
      significant difference between the TAC group and the fasudil-treated TAC group.
      Inhibition of ROCK exhibited reduced interstitial fibrosis, which was observed
      both in TAC and MI mice (P<0.05). The beneficial effects of fasudil were closely
      associated with the change of the specific profibrotic gene expression and TGF
      beta1-TAK1 pathway. Taken together, these results indicate that Rho-kinase is
      substantially involved in the myocardial remodeling after TAC and MI associated
      with upregulation of profibrotic gene expression and TGF-beta1-TAK1 pathway;
      further suggest the protective effect of fasudil on heart against pathological
      stimuli by inhibiting reactive fibrosis.

PMID- 22465605
TI  - Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro
      cardio-facio-cutaneous syndromes. Genotype and cardiopathy.
AB  - INTRODUCTION AND OBJECTIVES: Molecular characterization of congenital heart
      diseases now includes the not infrequent dysmorphic Noonan syndrome. A study of 6
      genes of the RAS-MAPK pathway in Spanish patients is presented: the impact of
      heart disease, clinical expressivity, and diagnostic yield are investigated.
      METHODS: The study included 643 patients (and 182 family members) diagnosed by
      dysmorphologists, cardiologists, and pediatric endocrinologists from 74 tertiary
      hospitals. Bidirectional sequencing analysis of PTPN11, SOS1, RAF1, BRAF, KRAS
      and HRAS focused on exons carrying recurrent mutations accounting for 80% to 95%
      of previously described mutations. RESULTS: Mutations were detected in 230
      patients (91 women and 139 men) in 200 (31%) families (172 PTPN11+, 14 SOS1+, 9
      RAF1+, 5 BRAF+). There was specific reference to the heart defect suffered in 156
      index cases: 103 patients had shown pulmonary stenosis, 12 pulmonary stenosis
      with hyperthrophic cardiomyopathy, 18 hypertrophic cardiomiopathy, and 14 other
      cardiopathies; heart disease was absent in 9 index cases. Heart disease had not
      been documented in 23 of 30 family members with positive genotype and compatible
      clinical signs. Diagnostic yield was higher (P=.016) for samples from some
      centers (53%; 14/32) and even from certain professionals (64%; 9/14; P=.019).
      Characterization rate was 18% in patients for whom clinical data were not
      available. Genotyping led to a more precise diagnosis in 26 patients.
      CONCLUSIONS: Most patients (94%) with a positive genotype had known congenital
      heart disease, 79% pulmonary stenosis and 12% hyperthrophic cardiomyopathy.
      Cardiopathy had not been documented in 76% of family members carrying the
      mutation. Molecular study is a useful tool in these syndromes but a more rigorous
      clinical diagnosis should be intended as well.

PMID- 22465608
TI  - Comparison of dual-axis rotational coronary angiography (XPERSWING) versus
      conventional technique in routine practice.
AB  - INTRODUCTION AND OBJECTIVES: Coronary angiography is the gold standard for the
      study of coronary artery disease. This technique requires several orthogonal
      projections. Rotational angiography is a new technique which involves pre-set
      rotation of the X-ray tube around the patient and allows visualization of each
      coronary artery in different views, using a single contrast injection. The
      purpose of this study was to compare conventional coronary angiography (A) vs
      rotational angiography (B), focusing on radiation dose, amount of contrast
      administered, and total procedure time for both diagnostic and therapeutic
      percutaneous coronary interventions. METHODS: Prospective study of 104
      consecutive patients undergoing coronary angiography who were randomized to one
      of these techniques. RESULTS: We found a significant reduction in the amount of
      contrast administered (A vs B, 93.1 [41.7] vs 50.9 [14.7] mL; P<.0001) and
      radiation exposure (27.6 [11.5] vs 18 [6.4] mGycm(2); P<.0001). A significant
      increase in total procedure time was noted in the rotational angiography arm.
      However, when only the last 50 patients were analyzed, we found no difference in
      procedure time between the groups, probably related to the learning curve of the
      operators. Angioplasty was performed in 29 patients in group A and 28 patients in
      group B. Contrast reduction was maintained in the rotational angiography group
      compared to the conventional technique (A vs B, 335.1 [192.1] vs 238.5 [114.4]
      mL; P=.02). CONCLUSIONS: The rotational angiography technique leads to a
      significant decrease in radiation exposure and contrast dose administered for
      diagnostic procedures when compared to conventional coronary angiography. In
      patients who undergo percutaneous coronary intervention, contrast reduction
      remains significant.

PMID- 22465609
TI  - The complex basis underlying common fragile site instability in cancer.
AB  - Common fragile sites (CFSs) were characterized almost 30 years ago as sites
      undergoing genomic instability in cancer. Recently, in vitro studies have found
      that oncogene-induced replication stress leads to CFS instability. In vivo, CFSs
      were found to be preferentially unstable during early stages of cancer
      development and to leave a unique signature of instability. It is now
      increasingly clear that, along the spectrum of replication features
      characterizing CFSs, failure of origin activation is a common feature. This and
      other features of CFSs, together with the replication stress characterizing early
      stages of cancer development, lead to incomplete replication that results in
      genomic instability preferentially at CFSs. Here, we review the shared and unique
      characteristics of CFSs, their underlying causes and their implications,
      particularly with respect to the development of cancer.

PMID- 22465612
TI  - Potential of the insect growth regulator, fluazuron, in the control of
      Rhipicephalus sanguineus nymphs (Latreille, 1806) (Acari: Ixodidae):
      determination of the LD95 and LD50.
AB  - Conventional pesticides have suffered two main drawbacks: (a) broad spectrum of
      action and (b) selection of target species resistant to the different active
      ingredients. Thus compounds that are less harmful to the environment and to human
      health, more specific and that do not induce resistance need to be developed. One
      alternative are insect growth regulators, such as fluazuron. The present study
      examined the efficacy of fluazuron (active ingredient of the acaricide Acatak(r))
      and the sensitivity of Rhipicephalus sanguineus nymphs exposed to different doses
      of this chemical, and determined the lethal doses of fluazuron: 95% - LD(95) and
      50% - LD(50). Different doses of fluazuron were applied in duplicates on the
      dorsal region of hosts ("pour on"). Distilled water was used in the control
      group. On the first day after the treatment with fluazuron, hosts were
      artificially infested with R. sanguineus nymphs. After engorgement, nymphs were
      removed, placed on Petri dishes, identified, and maintained in BOD incubator for
      15days. Dead R. sanguineus nymphs after the treatment with 13 different doses of
      fluazuron were quantified and the LD(95) was estimated to be 100mg/kg and LD(50),
      19.544mg/kg (12.478-22.636), with a confidence interval of 95%. Nymphs of R.
      sanguineus were sensitive to fluazuron at various levels, indicating that this
      insect growth regulator (IGR) may be used to control this parasite in this stage
      of its biological cycle, reducing the significant damage it causes.

PMID- 22465611
TI  - Characterization of a Trypanosoma brucei Alkb homolog capable of repairing
      alkylated DNA.
AB  - Trypanosoma brucei encodes a protein (denoted TbABH) that is homologous to AlkB
      of Escherichia coli and AlkB homolog (ABH) proteins in other organisms, raising
      the possibility that trypanosomes catalyze oxidative repair of alkylation-damaged
      DNA. TbABH was cloned and expressed in E. coli, and the recombinant protein was
      purified and characterized. Incubation of anaerobic TbABH with Fe(II) and alpha
      ketoglutarate (alphaKG) produces a characteristic metal-to-ligand charge-transfer
      chromophore, confirming its membership in the Fe(II)/alphaKG dioxygenase
      superfamily. The protein binds to DNA, with a clear preference for alkylated
      oligonucleotides according to results derived by electrophoretic mobility shift
      assays. Finally, the protozoan gene was shown to partially complement E. coli
      alkB cells when stressed with methylmethanesulfonate; thus confirming assignment
      of TbABH as a functional AlkB protein in T. brucei.

PMID- 22465610
TI  - Overcoming the nucleosome barrier during transcript elongation.
AB  - RNA polymerase II (Pol II) must break the nucleosomal barrier to gain access to
      DNA and transcribe genes efficiently. New single-molecule techniques have
      elucidated many molecular details of nucleosome disassembly and what happens once
      Pol II encounters a nucleosome. Our review highlights mechanisms that Pol II
      utilizes to transcribe through nucleosomes, including the roles of chromatin
      remodelers, histone chaperones, post-translational modifications of histones,
      incorporation of histone variants into nucleosomes, and activation of the
      poly(ADP-ribose) polymerase (PARP) enzyme. Future studies need to assess the
      molecular details and the contribution of each of these mechanisms, individually
      and in combination, to transcription across the genome to understand how cells
      are able to regulate transcription in response to developmental, environmental
      and nutritional cues.

PMID- 22465613
TI  - Influence of Trypanosoma evansi in adenine nucleotides and nucleoside
      concentration in serum and cerebral cortex of infected rats.
AB  - This study aimed to evaluate the adenine nucleotides and nucleoside concentration
      in serum and cerebral cortex of rats infected with Trypanosma evansi. Each rat
      was intraperitoneally infected with 1 * 10(6) trypomastigotes suspended in
      cryopreserved blood (Group A; n = 18). Twelve animals were used as controls
      (Group B). The infected animals were monitored daily by blood smears. At days 4
      and 20 post-infection (PI) it was collected serum and cerebral cortex to measure
      the levels of ATP, ADP, AMP and adenosine by high performance liquid
      chromatography (HPLC). In serum there was a significant (P < 0.05) increase in
      the ATP, AMP and adenosine concentrations at days 4 and 20 PI in infected rats
      when compared to not-infected. Furthermore, in the cerebral cortex it was
      observed a significant (P < 0.05) increase in the concentrations of ATP, AMP and
      decreased adenosine levels at day 4 PI. At day 20 PI it was only observed an
      increase in the AMP and adenosine concentrations in cerebral cortex of infected
      rats when compared to not-infected. It was not observed any difference in ADP
      concentration in serum and brain at days 4 and 20 PI. No change was observed
      histologically in the cerebral cortex of infected animals. The results allow us
      to conclude that infection with T. evansi in rats causes an increase in the
      concentrations of ATP, AMP and adenosine in serum and cerebral cortex the time
      periods evaluated. These alterations occurred as a result of T. evansi infection
      which involves neurotransmission, neuromodulation and immune response impairment
      confirm the importance of the purinergic system in this pathology.

PMID- 22465614
TI  - Mitochondrial transcription factor A regulates mitochondrial transcription
      initiation, DNA packaging, and genome copy number.
AB  - Mitochondrial transcription factor A (mtTFA, mtTF1, TFAM) is an essential protein
      that binds mitochondrial DNA (mtDNA) with and without sequence specificity to
      regulate both mitochondrial transcription initiation and mtDNA copy number. The
      abundance of mtDNA generally reflects TFAM protein levels; however, the precise
      mechanism(s) by which this occurs remains a matter of debate. Data suggest that
      the usage of mitochondrial promoters is regulated by TFAM dosage, allowing TFAM
      to affect both gene expression and RNA priming for first strand mtDNA
      replication. Additionally, TFAM has a non-specific DNA binding activity that is
      both cooperative and high affinity. TFAM can compact plasmid DNA in vitro,
      suggesting a structural role for the non-specific DNA binding activity in genome
      packaging. This review summarizes TFAM-mtDNA interactions and describes an
      emerging view of TFAM as a multipurpose coordinator of mtDNA transactions, with
      direct consequences for the maintenance of gene expression and genome copy
      number. This article is part of a Special Issue entitled: Mitochondrial Gene
      Expression.

PMID- 22465615
TI  - Previous administration of naltrexone did not change synergism between
      paracetamol and tramadol in mice.
AB  - In the treatment of acute and chronic pain the most frequently used drugs are
      nonsteroidal anti-inflammatory drugs (NSAIDs), e.g., paracetamol; opioids, e.g.,
      tramadol, and a group of drugs called coanalgesics or adjuvants (e.g.,
      antidepressants, anticonvulsants). The aim of this work was to determine the
      nature of the interaction induced by intraperitoneal or intrathecal
      coadministration of paracetamol and tramadol. The type of interaction was
      evaluated by means of isobolographic analysis, using the acetic acid writhing
      test as an algesiometer in mice. In addition, the involvement of opioid receptors
      in the interaction was studied using naltrexone, a non-selective opioid receptor
      antagonist. The administration of paracetamol or tramadol induced a dose
      dependent antinociceptive activity in the assay. The dose-response curves were
      characterized by equal efficacy but different potencies, being i.t. paracetamol
      11.84 times more potent than i.p. paracetamol, and i.t. tramadol 3.54 times more
      potent than the i.p. tramadol. The isobolographic analysis indicates a
      synergistic interaction between the coadministration of i.p. or i.t. paracetamol
      with tramadol. The interaction index values were similar for the i.p. and i.t.
      coadministration with values of 0.414 and 0.364, respectively. The different
      mechanisms of action of paracetamol and tramadol strongly explain the analgesic
      synergism between them, in agreement with the general theory of drug interaction.
      This synergic interaction was not modified by the non selective opioid
      antagonist, naltrexone. This association could be of clinical significance in the
      treatment of pain with a reduction of doses and adverse effects.

PMID- 22465616
TI  - The effect of levodopa on pulmonary function in Parkinson's disease: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Levodopa is considered the gold standard therapy for Parkinson's
      disease (PD). Aspiration pneumonia is the most frequent cause of death among PD
      patients. Asymptomatic respiratory impairment can be detected even in the initial
      stages of the disease course; however, there is no conclusive evidence regarding
      the efficacy of levodopa, the main therapeutic drug for PD, to enhance pulmonary
      function in these patients. OBJECTIVE: The aim of this systematic review and meta
      analysis was to evaluate the effects of levodopa therapy on respiratory
      parameters in patients with PD. METHODS: After a comprehensive and systematic
      literature search in the electronic databases MEDLINE, Embase, the Cochrane
      Library, and Web of Science, all trials referring to levodopa and respiratory
      function that met the eligibility criteria were included in the analysis.
      Considered outcomes were forced vital capacity (FVC), forced expiratory volume in
      1 second (FEV(1)), the ratio between FEV(1) and FVC (FEV(1)/FVC), and peak
      expiratory flow (PEF). The fixed effects model was used to assess the weighted
      mean difference, and heterogeneity between studies was calculated with the I(2)
      test. RESULTS: Four clinical trials comprising 73 patients and assessing the
      effects of levodopa on pulmonary function in patients with PD were included in
      the analysis. Pooled data showed that levodopa significantly improved FVC (SMD,
      0.40; P = 0.02) and PEF (standard mean difference, 0.39; P = 0.03). No
      significant change was observed with FEV(1) (SMD, 0.34; P = 0.05) or the
      FEV(1)/FVC ratio (standard mean difference, -0.08; P = 0.66) after levodopa
      therapy. CONCLUSIONS: The results of this systematic review suggest that levodopa
      therapy improved FVC and PEF, whereas no changes were observed in FEV(1) and
      FEV(1)/FVC. These findings may provide some indirect evidence regarding the
      efficacy of levodopa in restrictive parameters of pulmonary function.

PMID- 22465617
TI  - Variations in cell morphology in the canine cruciate ligament complex.
AB  - Cell morphology may reflect the mechanical environment of tissues and influence
      tissue physiology and response to injury. Normal cruciate ligaments (CLs) from
      disease-free stifle joints were harvested from dog breeds with a high (Labrador
      retriever) and low (Greyhound) risk of cranial cruciate ligament (CCL) rupture.
      Antibodies against the cytoskeletal components vimentin and alpha tubulin were
      used to analyse cell morphology; nuclei were stained with 4',6-diamidino-2
      phenylindole, and images were collected using conventional and confocal
      microscopy. Both cranial and caudal CLs contained cells of heterogenous
      morphologies. Cells were arranged between collagen bundles and frequently had
      cytoplasmic processes. Some of these processes were long (type A cells), others
      were shorter, thicker and more branched (type B cells), and some had no processes
      (type C cells). Processes were frequently shown to contact other cells, extending
      longitudinally and transversely through the CLs. Cells with longer processes had
      fusiform nuclei, and those with no processes had rounded nuclei and were more
      frequent in the mid-substance of both CLs. Cells with long processes were more
      commonly noted in the CLs of the Greyhound. As contact between cells may
      facilitate direct communication, variances in cell morphology between breeds at a
      differing risk of CCL rupture may reflect differences in CL physiology.

PMID- 22465618
TI  - Effects of a stepwise lung recruitment manoeuvre and positive end-expiratory
      pressure on lung compliance and arterial blood oxygenation in healthy dogs.
AB  - This study was performed to evaluate the effects of a stepwise lung recruitment
      manoeuvre (RM) on dynamic lung compliance (Cdyn) and gas exchange in mechanically
      ventilated healthy dogs. Fourteen healthy adult dogs, scheduled for elective
      surgery in dorsal recumbency were employed. After anaesthetic induction, dogs
      were mechanically ventilated in a volume-controlled mode (tidal volume, VT=10
      mL/kg); positive end-expiratory pressure (PEEP)=0 cm H(2)O; oxygen inspired
      fraction (FiO(2))=0.4 for 30 min (baseline). The dogs were then randomly
      allocated into two groups, control and RM. The ventilatory mode was maintained
      during the whole surgical procedure in the control group without any
      intervention, as in general practice. The RM was performed in a pressure
      controlled mode, with progressive increases of PEEP and end-inspiratory pressure
      of 5 cm H(2)O until 15 cm H(2)O and 30 cm H(2)O, respectively. After RM, PEEP was
      decreased to 4 cm H(2)O, and the ventilatory mode was returned to volume-control.
      Arterial blood gases and Cdyn were determined at baseline, 20 and 60 min
      afterwards. Student's t test and the one-way ANOVA test were employed to compare
      data. Cdyn increased in the RM group (183 +/- 30% and 165 +/- 24% at 20 and 60
      min, respectively; P=0.000). The baseline partial pressure of arterial oxygen to
      FiO(2) ratio (PaO(2)/FiO(2) ratio) did not change in the control group, but was
      higher in the RM group (527 +/- 41 mm Hg and 511 +/- 46 mm Hg at 20 and 60 min,
      respectively; baseline 371 +/- 34 mm Hg, P<0.001). In conclusion, a stepwise RM
      followed by the use of PEEP improves Cdyn and oxygenation in mechanically
      ventilated healthy dogs.

PMID- 22465619
TI  - Functional neuroimaging studies of sexual arousal and orgasm in healthy men and
      women: a review and meta-analysis.
AB  - In the last fifteen years, functional neuroimaging techniques have been used to
      investigate the neuroanatomical correlates of sexual arousal in healthy human
      subjects. In most studies, subjects have been requested to watch visual sexual
      stimuli and control stimuli. Our review and meta-analysis found that in
      heterosexual men, sites of cortical activation consistently reported across
      studies are the lateral occipitotemporal, inferotemporal, parietal,
      orbitofrontal, medial prefrontal, insular, anterior cingulate, and frontal
      premotor cortices as well as, for subcortical regions, the amygdalas, claustrum,
      hypothalamus, caudate nucleus, thalami, cerebellum, and substantia nigra.
      Heterosexual and gay men show a similar pattern of activation. Visual sexual
      stimuli activate the amygdalas and thalami more in men than in women. Ejaculation
      is associated with decreased activation throughout the prefrontal cortex. We
      present a neurophenomenological model to understand how these multiple regional
      brain responses could account for the varied facets of the subjective experience
      of sexual arousal. Further research should shift from passive to active
      paradigms, focus on functional connectivity and use subliminal presentation of
      stimuli.

PMID- 22465620
TI  - Abnormal plasma microparticles impair vasoconstrictor responses in patients with
      cirrhosis.
AB  - BACKGROUND & AIMS: Circulating membrane-shed microparticles (MPs) participate in
      regulation of vascular tone. We investigated the cellular origins of MPs in
      plasma from patients with cirrhosis and assessed the contribution of MPs to
      arterial vasodilation, a mechanism that contributes to portal hypertension.
      METHODS: We analyzed MPs from blood samples of 91 patients with cirrhosis and 30
      healthy individuals (controls) using flow cytometry; their effects on the
      vascular response to vasoconstrictors were examined in vitro and in vivo.
      RESULTS: Circulating levels of leuko-endothelial (CD31(+)/41(-)), pan-leukocyte
      (CD11a(+)), lymphocyte (CD4(+)), and erythrocyte (CD235a(+)) MPs were higher in
      patients with cirrhosis than in controls. Plasma of patients with cirrhosis
      contained hepatocyte-derived MPs (cytokeratin-18(+)), whereas plasma from
      controls did not. The severity of cirrhosis and systemic inflammation were major
      determinants of the levels of leuko-endothelial and hepatocyte MPs. MPs from
      patients with advanced cirrhosis significantly impaired contraction of vessels in
      response to phenylephrine, whereas MPs from healthy controls or from patients of
      Child-Pugh class A did not. This effect depended on cyclooxygenase type 1 and
      required phosphatidylserine on the surface of MPs. Intravenous injection of MPs
      from patients with cirrhosis into BALB/C mice decreased mean arterial blood
      pressure. CONCLUSIONS: Cirrhosis is associated with increases in circulating
      subpopulations of MPs, likely resulting from systemic inflammation and liver cell
      damage. The overall pool of circulating MPs from patients with advanced cirrhosis
      impairs vasoconstrictor responses and decreases blood pressure, contributing to
      the arterial vasodilation associated with portal hypertension.

PMID- 22465622
TI  - Diet-induced obese rats exhibit impaired LKB1-AMPK signaling in hypothalamus and
      adipose tissue.
AB  - AMPK not only acts as a sensor of cellular energy status but also plays a
      critical role in the energy balance of the body. In this study, LKB1-AMPK
      signaling was investigated in diet-induced obese (DIO) and diet resistant (DR)
      rats. In hypothalamus, DIO rats had lower level of LKB1, AMPKalpha and pAMPKalpha
      than chow-fed or DR rats. Both orexigenic peptide NPY and anorexigenic peptide
      POMC expression were reduced in hypothalamus of DIO rats. i.c.v. injection of
      AICAR, an activator of AMPK, increased NPY expression but did not alter POMC
      expression in DIO rats. In periphery, LKB1 protein content and pAMPKalpha level
      were lower in the adipose tissue of DIO rats compared to chow-fed and DR rats.
      Moreover, pAMPKalpha and LKB1 protein levels obtained from epididymal fat pad
      were inversely correlated with epididymal fat mass. LKB1 protein content and
      pAMPKalpha in skeletal muscle of DIO rats were not different from those in the
      muscles of chow-fed and DR rats. In summary, DIO rats, but not DR rats, have
      impaired LKB1-AMPK signaling in hypothalamus and adipose tissue, suggesting the
      disturbed energy balance observed in DIO rats is related with abnormalities of
      AMPK signaling in a tissue specific manner.

PMID- 22465621
TI  - Novel peptide for attenuation of hypoxia-induced pulmonary hypertension via
      modulation of nitric oxide release and phosphodiesterase -5 activity.
AB  - Pulmonary vascular endothelial nitric oxide (NO) synthase (eNOS)-derived NO is
      the major stimulant of cyclic guanosine 5'-monophosphate (cGMP) production and
      NO/cGMP-dependent vasorelaxation in the pulmonary circulation. We recently
      synthesized multiple peptides and reported that an eleven amino acid
      (SSWRRKRKESS) peptide (P1) but not scrambled P1 stimulated the catalytic activity
      but not expression of eNOS and causes NO/cGMP-dependent sustained vasorelaxation
      in isolated pulmonary artery (PA) segments and in lung perfusion models. Since
      cGMP levels can also be elevated by inhibition of phosphodiesterase type 5 (PDE
      5), this study was designed to test the hypothesis that P1-mediated
      vesorelaxation is due to its unique dual action as NO-releasing PDE-5 inhibitor
      in the pulmonary circulation. Treatment of porcine PA endothelial cells (PAEC)
      with P1 caused time-dependent increase in intracellular NO release and inhibition
      of the catalytic activity of cGMP-specific PDE-5 but not PDE-5 protein expression
      leading to increased levels of cGMP. Acute hypoxia-induced PA vasoconstriction ex
      vivo and continuous telemetry monitoring of hypoxia (10% oxygen)-induced elevated
      PA pressure in freely moving rats were significantly restored by administration
      of P1. Chronic hypoxia (10% oxygen for 4 weeks)-induced alterations in PA
      perfusion pressure, right ventricular hypertrophy, and vascular remodeling were
      attenuated by P1 treatment. These results demonstrate the potential therapeutic
      effects of P1 to prevent and/or arrest the progression of hypoxia-induced PAH via
      NO/cGMP-dependent modulation of hemodynamic and vascular remodeling in the
      pulmonary circulation.

PMID- 22465623
TI  - Hypothalamic gonadotropin-inhibitory hormone precursor mRNA is increased during
      depressed food intake in heat-exposed chicks.
AB  - The regulation of food intake in chickens (Gallus gallus domesticus) represents a
      complex homeostatic mechanism involving multiple levels of control, and
      regulation during high ambient temperatures (HT) is poorly understood. In this
      study, we examined hypothalamic mRNA expression of gonadotropin-inhibitory
      hormone (GnIH) to understand the effect of HT on an orexigenic neuropeptide. We
      examined the effects of HT (35  degrees C ambient temperature for 1, 24 or 48 h)
      on 14-day old chicks. HT significantly increased rectal temperature and
      suppressed food intake, and also influenced plasma metabolites. The expression of
      GnIH precursor mRNA in the diencephalon was significantly increased in chicks at
      24-and 48 h of HT when food intake was suppressed significantly, whilst no change
      was observed for GnIH precursor mRNA and food intake at 1h of HT. In situ
      hybridization and immunocytochemistry further revealed the cellular localization
      of chicken GnIH precursor mRNA and its peptide in the paraventricular nucleus
      (PVN) in the chick hypothalamus. We examined plasma metabolites in chicks exposed
      to HT for 1 or 48 h and found that triacylglycerol concentration was
      significantly higher in HT than control chicks at 1h. Total protein, uric acid
      and calcium were significantly lower in HT chicks than control chicks at 48h.
      These results indicate that not only a reduction in food intake and alteration in
      plasma metabolites but also the PVN-specific expression of GnIH, an orexigenic
      agent, may be induced by HT. The reduced food intake at the same time as GnIH
      expression was increased during HT suggests that HT-induced GnIH expression may
      oppose HT-induced feeding suppression, rather than promote it. We suggest that
      the increased GnIH expression could be a consequence of the reduced food intake,
      and would not be a direct response to HT.

PMID- 22465624
TI  - Oxidative stress in surgery in an ageing population: pathophysiology and therapy.
AB  - Reactive oxygen species (ROS) play an important role in the regulation of normal
      cellular function. When ROS are produced in excess they can have detrimental
      effects, a state known as oxidative stress. Thus ROS play both physiological and
      pathophysiological roles in the body. In clinical practice oxidative stress and
      its counterpart, antioxidant capacity can be measured and can guide remedial
      therapy. Oxidative stress can have a negative impact in all forms of major
      surgery including cardiac surgery, general surgery, trauma surgery, orthopedic
      surgery and plastic surgery; this is particularly marked in an ageing population.
      Many different therapies to reduce oxidative stress in surgery have been tried
      with variable results. We conclude that in surgical patients the assessment of
      oxidative stress, improvement of the understanding of its role, both positive and
      negative, and devising appropriate therapies represent fruitful fields for future
      research.

PMID- 22465625
TI  - Markerless Roentgen Stereophotogrammetric Analysis for in vivo implant migration
      measurement using three dimensional surface models to represent bone.
AB  - Recent studies have shown that model-based RSA using implant surface models to
      detect in vivo migration is as accurate as the classical marker-based RSA method.
      Use of bone surface models would be a further advancement of the model-based
      method by decreasing complications arising from marker insertion. The aim of this
      pilot investigation was to assess the feasibility of a "completely markerless"
      model-based RSA in detecting migration of an implant using bone surface models
      instead of bone markers. A total knee arthroplasty (TKA) was performed on a human
      cadaver knee, which was subsequently investigated by repeated RSA measurements
      performed by one observer. The cadaver knee was CT scanned prior to implantation
      of the TKA. Tibia-fibular surface models were created using two different
      commercially available software packages to investigate the effect of
      segmentation software on the accuracy of repeated migration measures of zero
      displacement by one observer. Reverse engineered surface models of the TKA tibial
      component were created. The analysis of the RSA images was repeated 10 times by
      one individual observer. For the markerless method, the greatest apparent
      migration observed about the three anatomical axes investigated was between -2.08
      and 1.35 mm (SD <= 0.88) for z-axis translation, and -4.57 degrees  to 7.86
      degrees  (SD <= 3.17) for R(y)-axis rotation, which were well beyond out of the
      range of what is typically considered adequate for clinically relevant RSA
      measurements. Use of tibia-fibular surface models of the bone instead of markers
      could provide practical advantages in evaluating implant migration. However, we
      found the accuracy and precision of the markerless approach to be lower than that
      of marker-based RSA, to a degree which precludes the use of this method for
      measuring implant migration in its present form.

PMID- 22465626
TI  - Letter to the editor regarding "Effect of low pass filtering on joint moments
      from inverse dynamics: implications for injury prevention".

PMID- 22465627
TI  - The rectal glands of Heterorhabditis bacteriophora (Rhabditida:
      Heterorhabditidae) hermaphrodites and their role in symbiont transmission.
AB  - Differential interference contrast, transmission electron and epifluorescence
      microscopy techniques were employed to examine the ultrastructure of the rectal
      glands in Heterorhabditis bacteriophora hermaphrodites, with special attention to
      the location of Photorhabdus bacteria symbionts within these structures. Three
      rectal glands were clearly visualized in all examined specimens, with two glands
      positioned sub-ventrally and another gland located dorsally. The dorsal rectal
      gland in all examined specimens is larger than the subventral ones. Our
      observations indicate that Photorhabdus bacteria do not colonize the rectal
      glands of H. bacteriophora hermaphrodites, but rather are present in the most
      posterior-intestinal cells.

PMID- 22465628
TI  - Natural and cultured populations of the mangrove oyster Saccostrea palmula from
      Sinaloa, Mexico, infected by Perkinsus marinus.
AB  - The mangrove oyster Saccostrea palmula coexists with the pleasure oyster
      Crassostrea corteziensis in coastal lagoons of northwest Mexico. Recent discovery
      of Perkinsus marinus infecting the pleasure oyster in the region prompted
      evaluation of S. palmula as an alternative P. marinus host. An analysis to
      determine the possible presence of P. marinus in natural and cultured populations
      of S. palmula at four coastal lagoons in Sinaloa, Mexico was carried out during
      October-November 2010. Tissues from apparently healthy S. palmula were evaluated
      using Ray's fluid thioglycollate method (RFTM), which revealed a Perkinsus sp. to
      be present in all four locations at 6.7-20.0% prevalence. Histopathological
      analysis of these specimens showed tissue alterations and parasite forms
      consistent with moderate P. marinus infection, which was confirmed by ribosomal
      non-transcribed spacer (NTS)-based PCR assays on DNA samples from oysters
      positive by RFTM and histology. DNA sequencing of amplified NTS fragments (307
      bp) produced a sequence 98-100% similar to GenBank-deposited sequences of the NTS
      from P. marinus. Fluorescent in situ hybridization for Perkinsus spp. and P.
      marinus corroborated the PCR results, showing clear hybridization of P. marinus
      in host tissues. This is the first record of P. marinus infecting a species from
      genus Saccostrea and the first record of the parasite from coastal lagoons in
      Sinaloa, Mexico.

PMID- 22465629
TI  - Analysis of the structural proteins from the Musca domestica hytrosavirus with an
      emphasis on the major envelope protein.
AB  - The Musca domestica hytrosavirus (MdHV), a member of the family Hyrosaviridae, is
      a large, dsDNA, enveloped virus that infects adult house flies and causes a
      diagnostic hypertrophy of the salivary gland. Herein, studies were directed at
      identifying key structural components of the viral envelope and nucleocapsid. SDS
      PAGE of detergent-treated virus fractions identified protein bands unique to the
      envelope and nucleocapsid components. Using prior LC-MSMS data we identified the
      viral ORF associated with the major envelope band, cloned and expressed
      recombinant viral antigens, and prepared a series of polyclonal sera. Western
      blots confirmed that antibodies recognized the target viral antigen and provided
      evidence that the viral protein MdHV96 underwent post-translational processing;
      antibodies bound to the target high molecular weight parent molecule as well as
      distinct sets of smaller bands. Immuno gold electron microscopy demonstrated that
      the anti-MdHV96 sera recognized target antigens associated with the envelope. The
      nucleocapsids migrated from the virogenic stroma in the nucleus through the
      nuclear membrane into the cytoplasm, where they acquired an initial envelope that
      contained MdHV96. This major envelope protein, appeared to incorporate into
      intracellular membranes of both the caniculi and rough endoplasmic reticulum
      membranes and mediate binding to the nucleocapsids. Oral infection bioassays
      demonstrated that the anti-HV96 polyclonal sera acted as neutralizing agents in
      suppressing the levels of orally acquired infections.

PMID- 22465630
TI  - New prospective in treatment of Parkinson's disease: studies on permeation of
      ropinirole through buccal mucosa.
AB  - The aptitude of ropinirole to permeate the buccal tissue was tested using porcine
      mucosa mounted on Franz-type diffusion cells as ex vivo model. Drug permeation
      was also evaluated in presence of various penetration enhancers and in
      iontophoretic conditions. Ropinirole, widely used in treatment of motor
      fluctuations of Parkinson's disease, passes the buccal mucosa. Flux and
      permeability coefficient values suggested that the membrane does not appear a
      limiting step to the drug absorption. Nevertheless, an initial lag time is
      observed but the input rate can be modulated by permeation enhancement using
      limonene or by application of electric fields. Absorption improvement was
      accompanied by the important reduction of the lag time; at once the time required
      to reach the steady state plasma concentration was drastically decreased. On the
      basis of these results we could assume that clinical application of ropinirole by
      buccal delivery is feasible.

PMID- 22465631
TI  - Application of face centred central composite design to optimise compression
      force and tablet diameter for the formulation of mechanically strong and fast
      disintegrating orodispersible tablets.
AB  - A two factor, three level (3(2)) face centred, central composite design (CCD) was
      applied to investigate the main and interaction effects of tablet diameter and
      compression force (CF) on hardness, disintegration time (DT) and porosity of
      mannitol based orodispersible tablets (ODTs). Tablet diameters of 10, 13 and 15
      mm, and CF of 10, 15 and 20 kN were studied. Results of multiple linear
      regression analysis show that both the tablet diameter and CF influence tablet
      characteristics. A negative value of regression coefficient for tablet diameter
      showed an inverse relationship with hardness and DT. A positive value of
      regression coefficient for CF indicated an increase in hardness and DT with
      increasing CF as a result of the decrease in tablet porosity. Interestingly, at
      the larger tablet diameter of 15 mm, while hardness increased and porosity
      decreased with an increase in CF, the DT was resistant to change. The optimised
      combination was a tablet of 15 mm diameter compressed at 15 kN showing a rapid DT
      of 37.7s and high hardness of 71.4N. Using these parameters, ODTs containing
      ibuprofen showed no significant change in DT (ANOVA; p>0.05) irrespective of the
      hydrophobicity of the ibuprofen.

PMID- 22465632
TI  - Drug eluting sutures: a model for in vivo estimations.
AB  - This work is focused on the development of a transient 1-dimension model to
      describe drug release from a bioresorbable suture thread in a living tissue and
      the pharmacologic behavior of the active substance being delivered from the
      device into the tissue. The model is based on fundamental conservation laws,
      represented by mass balances, being the thread degradation described through
      population balances and involving detailed hydrolysis kinetics. Monomer, water
      and drug diffusion are assumed as Fickian, and the increasing of diffusion
      coefficient is expressed with the "free volume" theory. Drug behavior in tissue
      is described with a "diffusion and reaction" approach. The model leads to a
      system of partial differential equations solved by applying the method of lines
      and then numerically integrated. Simulations allowed to estimate release dynamics
      and drug behavior in tissue and to obtain spatial and temporal profiles of drug
      in tissue. Moreover, phase diagrams, which show drug effect in time and space,
      are here introduced for the first time.

PMID- 22465633
TI  - Development of a nanoparticle-based system for the delivery of retinoic acid into
      macrophages.
AB  - The aim of the present work is to prepare nanoparticulate systems that can target
      and modulate the functions of mononuclear phagocytes by local administration. All
      trans retinoic acid (RA) was chosen as an immunomodulator to be encapsulated in
      biodegradable nanoparticles (NP). Different formulations were prepared by the
      nanoprecipitation method and poly(d,l)lactic acid based nanocapsules (NC) were
      selected to continue the study. RA-NC demonstrated a sustained release profile
      and an enhanced stability for 7 days. The uptake of fluorescent (NileRed) labeled
      NP was conducted on bone marrow derived macrophages (BMM) in vitro and xenograft
      glioma nude mice in vivo. Fluorescent microscopy observations and flow cytometry
      analysis demonstrated that NR-NC were engulfed by BMM in vitro and lasted inside
      over 7 days. The intratumoral injection of NR-NC confirmed that NC were
      efficiently uptaken by infiltrated macrophages. The effects of RA loaded NC on
      BMM were also evaluated by RT(2)-PCR array. Our results suggest that polymeric
      nanoparticles are suitable carriers to deliver RA into macrophages and can offer
      a new strategy in tumor macrophage-based treatment.

PMID- 22465634
TI  - Anti-AIDS agents 89. Identification of DCX derivatives as anti-HIV and
      chemosensitizing dual function agents to overcome P-gp-mediated drug resistance
      for AIDS therapy.
AB  - In this study, 19 dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl
      dihydropyranoxanthone (DCX) derivatives, previously discovered as novel anti-HIV
      agents, were evaluated for their potential to reverse multi-drug resistance (MDR)
      in a cancer cell line over-expressing P-glycoprotein (P-gp). Seven compounds
      fully reversed resistance to vincristine (VCR) at 4 MUM, a 20-fold enhancement
      compared to the first generation chemosensitizer, verapamil (4 MUM). The
      mechanism of action of DCPs and DCXs was also resolved, since the most active
      compounds (3, 4, and 7) significantly increased intracellular drug accumulation
      due, in part, to inhibiting the P-gp mediated drug efflux from cells. We conclude
      that DCPs (3 and 4) and DCXs (7, 11, and 17) can exhibit polypharmacologic
      behavior by acting as dual inhibitors of HIV replication and chemoresistance
      mediated by P-gp. As such, they may be useful in combination therapy to overcome
      P-gp-associated drug resistance for AIDS treatment.

PMID- 22465635
TI  - Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families.
AB  - In an effort to identify multi-targeted kinase inhibitors with a novel spectrum
      of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad
      panel of kinases was conducted and revealed a series of thienopyridine ureas with
      promising activity against the Aurora kinases. Modification of the diphenyl urea
      and C7 moiety of these compounds provided potent inhibitors with good
      pharmacokinetic profiles that were efficacious in mouse tumor models after oral
      dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I
      clinical trials in solid and hematological cancer populations.

PMID- 22465636
TI  - Steroidal C-21 heteroaryl thioethers. Part 3: pregn-4-eno-[3,2-c]pyrazole fused A
      ring modified steroids as selective glucocorticoid receptor modulators
      (dissociated steroids).
AB  - The introduction of A ring pyrazole modification to the hydrocortisone C-21
      heteroaryl thioethers generated compounds with excellent transrepression potency
      (IL-8 inhibition) compared to their hydrocortisone analogs. However, the
      transcriptional transactivation activity of these compounds were considerably
      higher than the corresponding hydrocortisone analogs. Among all the compounds
      evaluated, a quinoxaline thioether modification demonstrated the best overall in
      vitro separation.

PMID- 22465637
TI  - 4-(1-Phenyl-1H-pyrazol-4-yl)quinolines as novel, selective and brain penetrant
      metabotropic glutamate receptor 4 positive allosteric modulators.
AB  - 4-(1-Phenyl-1H-pyrazol-4-yl)quinoline (1) was identified by screening the
      Lundbeck compound collection, and characterized as having mGlu4 receptor positive
      allosteric modulator properties. Compound 1 is selective over other mGlu
      receptors and a panel of GPCRs, ion channels and enzymes, but has suboptimal
      lipophilicity and high plasma and brain non-specific binding. In view of the
      challenges at the hit-to-lead stage previously reported in the development of
      mGlu4 receptor positive allosteric modulators (PAMs), a thorough structure-mGlu4
      PAM activity relationship study was conducted to interrogate the chemical
      tractability of this chemotype. The central pyrazole ring tolerates the addition
      of one or two methyl groups. The C-7 position of the quinoline ring provides a
      site tolerant to hydrophilic substituents, enabling the design of diverse analogs
      with good in vitro mGlu4 PAM potency and efficacy, as well as improved microsomal
      turnover in vitro, compared to 1. In spite of the excellent ligand efficiency of
      1 (LE=0.43), optimization of in vitro potency for this series reached a plateau
      around EC(50)=200 nM.

PMID- 22465638
TI  - The future of combining inhaled drugs for COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality globally, and its prevalence is projected to continue to increase owing
      to trends in smoking. Treatment of COPD has evolved from the initial adaptations
      of drugs and treatment strategies successfully used in asthma into more specific
      pharmacological strategies following global guidelines. Bronchodilating
      anticholinergic and beta-2-stimulating agents and anti-inflammatory
      corticosteroid drugs delivered by inhalators are the mainstay of COPD treatment.
      Despite significant progress, current pharmacotherapies neither fully alleviate
      the airway obstruction in COPD, nor reverse the progressive nature of the
      disease. This review discusses inhalation therapies which have recently become
      clinically available or are being developed, with focus on combination therapies.
      There is accumulating evidence that the combination of two or all three drug
      classes, triple therapy, is superior to single drug therapy. Several fixed
      combinations of both currently available and novel molecules will be launched for
      clinical use within the next few years. Also, improved understanding of subgroups
      within the clinical spectrum of COPD, is likely to offer new potentials to
      improve COPD care.

PMID- 22465639
TI  - mfERG_LAB: Software for processing multifocal electroretinography signals.
AB  - The multifocal electroretinography technique consists of performing sectorized
      light excitation of the retina and capturing the resulting evoked potential. This
      provides functional localized information about the state of the retinal neurons.
      Analysis of multifocal electroretinography signals can be used for diagnosing
      different types of optic neuropathies (glaucomatous, demyelinating and ischemic
      ethiology). In order to obtain a reliable diagnosis, it is necessary to apply
      advanced processing algorithms (morphological, frequency and time-frequency
      analysis, etc.) to the multifocal electroretinography signal. This paper presents
      a software application developed in MATLAB((r)) (MathWorks Inc., MA) designed to
      perform advanced multifocal electroretinography signal analysis and
      classification. This intuitive application, mfERG_LAB, is used to plot the
      signals, apply various algorithms to them and present the data in an appropriate
      format. The application's computational power and modular structure make it
      suitable for use in clinical settings as a powerful and innovative diagnostic
      tool, as well as in research and teaching settings as a means of assessing new
      algorithms.

PMID- 22465640
TI  - System approach to modeling of liver glucose metabolism with physiologically
      interpreted model parameters outgoing from [18F]FDG concentrations measured by
      PET.
AB  - New mathematical models from physiologically interpreted parameters capable of
      evaluating glucose metabolism within the liver and/or the whole body were
      developed. The group of pigs in a fasting state and the group of pigs with
      euglycemic supraphysiological hyperinsulinemia were scanned by positron emission
      tomography after a single dose of [(18)F]FDG tracer. Simultaneously frequent
      sampling of the dynamic data of [(18)F]FDG plasma concentration in artery, portal
      vein and hepatic vein was obtained. A system approach to the liver and/or the
      whole-body system by the tools of linear dynamic sysztem theory was used. Three
      kinds of structural models, single input and single output or multiple outputs
      and multiple inputs and single output, were identified. Differences between the
      group of fasting pigs and the group of pigs in euglycemic supraphysiological
      hyperinsulinemia were identified by estimated parameters of the structural
      models. The suitability of the structural mathematical models for the estimation
      of physiologically interpreted parameters from PET was validated.

PMID- 22465641
TI  - Shield kyphoplasty through a unipedicular approach compared to vertebroplasty and
      balloon kyphoplasty in osteoporotic thoracolumbar fracture: a prospective
      randomized study.
AB  - OBJECTIVE: Currently, there are no clinical studies comparing different cement
      augmentation methods, and no clinical observational studies of a unipedicular
      approach. DESIGN, PATIENTS, INTERVENTIONS, MAIN OUTCOME MEASUREMENTS: The present
      study compared three commercially available vertebral augmentation systems:
      balloon kyphoplasty, vertebroplasty and shield kyphoplasty. The primary objective
      was to assess change in subjective severity of backache on a visual analog scale
      (VAS) and subjective improvement in quality of life on the Oswestry Disability
      Index (ODI), at a mean 6 months post-surgery. The secondary objective was to
      analyze current radiological imaging (X-ray, and in some cases CT) with regard to
      height restoration, cement distribution and leakage and recurrent fracture.
      RESULTS: Mean follow-up was 5.8 months. Mean preoperative Beck vertebral height
      index did not significantly differ between the three augmentation system groups
      (P>0.05). Comparing surgery time, fluoroscopy time and dose-area-product (cGy *
      cm(2)) showed a statistically significant difference (P<0.01) in favor of the
      vertebroplasty technique. Augmentation provided significant improvement in VAS
      pain assessment, but with no significant difference between augmentation systems.
      Results on the ODI were less pronounced, with significant improvement of 22% to
      45%, but again without significant difference between augmentation systems.
      CONCLUSIONS: Overall, apart from mostly asymptomatic cement leakage,
      vertebroplasty could be considered as the surgical procedure of choice.

PMID- 22465642
TI  - [Acute negative pressure pulmonary edema: illustration from a unusual clinical
      case following a postoperative recurrent laryngeal nerve palsy].
AB  - Acute postoperative negative pressure pulmonary edema (NPPE) is a respiratory
      complication due to upper airway obstruction occurring most commonly in the
      postoperative period. Pathophysiologically, NPPE is explained by the abrupt
      generation of highly negative intrathoracic pressure that lead to fluid
      transudation from the pulmonary capillaries. This observation reports an unusual
      case of a young patient who has undergone total thyroidectomy for multinodular
      goiter. The postoperative period was marked by the occurrence of bilateral
      recurrent laryngeal nerve palsy that was complicated by a NPPE. The outcome was
      favorable after mechanical ventilation with reversal of NPPE and recovery of the
      recurrent laryngeal nerve function. This article stresses the importance of
      prevention of recurrent nerve palsy during thyroid surgery. It also highlights a
      little known respiratory complication: the NPPE. Understanding the
      pathophysiology of NPPE, rapid diagnosis and appropriate therapeutic measures
      could prevent its potential lethal consequences.

PMID- 22465643
TI  - [The perioperative period in cancer surgery: a critical moment! Is there a role
      for regional anesthesia in preventing cancer recurrence?].
AB  - Surgical treatment of cancer is usually necessary but it can paradoxically
      aggravate the patient outcome by increasing the risk of recurrence. Many
      perioperative factors have been shown to contribute to the dissemination of the
      tumor: surgery itself, stress, inflammation, pain, anaesthetic drugs, blood
      transfusion, etc. The type of anaesthesia chosen in the cancer patient could then
      be crucial and influence the evolution of the disease. Experimental, preclinical
      and retrospective studies have suggested that a regional anesthesia associated or
      not with a general anesthesia for carcinologic surgery might reduce the risk of
      cancer recurrence. This text reviews the factors promoting the recurrence of
      tumors after carcinologic surgery and the potential possibilities of protection
      associated with the type of anaesthesia chosen.

PMID- 22465644
TI  - [Announce a death rapes to the close relations in emergency situation and taken
      care].
AB  - The death is a part of the everyday life of the emergency medical teams, but to
      announce the death and to take care in immediate of the saddened close relations
      rest a testing experience for which the professionals of the emergency care are
      not still prepared. Our comment aims from the experience of care of families,
      saddened in immediate and also recorded within the framework of a specialized
      consultation, to pass on what the saddened persons can feel during the
      intervention of the help and the confrontation in the death of their close. Our
      objective being to bring to the professionals of the tracks of reflection to
      limit the risks of survictimisation.

PMID- 22465645
TI  - [Continuous haemodialysis with citrate anticoagulation in patients with liver
      failure: three cases].
AB  - Regional citrate anticoagulation for continuous renal replacement therapy
      provides an efficient alternative to heparin as it reduces the likelihood of
      haemorrhage in critically ill patients with bleeding risk or coagulopathy and
      increases the haemofilter survival time. Liver failure is a classic
      contraindication of regional citrate anticoagulation since it carries the risk of
      citrate accumulation and its metabolic complications, although it could be
      attractive for this population of patients with high bleeding risk. We report
      three cases of continuous haemodialysis with regional citrate anticoagulation
      performed in patients with severe acute liver failure, without accumulation in
      two cases and with a suspected beginning of accumulation in the third case. For
      these patients, close monitoring of the total-to-ionized calcium ratio, pH and
      anion gap is particularly essential to control the safety of citrate infusion.
      Increasing effluent flow rate eliminates more calcium-bound citrate and therefore
      limits citrate accumulation and its consequences.

PMID- 22465646
TI  - [Extensive mesenteric ischemia related to naratriptan overuse associated with
      grapefruit juice absorption].
AB  - We reported the case of a 61-year-old woman, who has been hospitalized in ICU
      because of an extensive mesenteric ischaemia, involving the small bowel,
      secondary to a naratriptan overuse. This mesenteric ischaemia was complicated by
      multiple organ failure and was responsible for extensive small bowel resection
      and left colectomy. A concomitant abundant absorption of grapefruit juice, a well
      known P450 inhibitor, may have enhanced this naratriptan toxicity. This case
      underscore that an abdominal pain occurring in the context of headache treatment
      may be related to a mesenteric ischaemia.

PMID- 22465647
TI  - [Spontaneous intracerebral haemorrhage secondary to congenital factor XIII
      deficiency].
AB  - Deficiency of coagulation factor XIII is a rare anomaly. The risk of intracranial
      haemorrhage is particularly high at any age, either spontaneously or during minor
      trauma. We report a case of spontaneous intracerebral haemorrhage in a child
      carrying a known deficiency of factor XIII.

PMID- 22465648
TI  - [Internal jugular venous cannulation: what is the best approach?].
AB  - OBJECTIVES: The aim of this study was to compare two approaches used for internal
      jugular venous cannulation: the anterior way, described by English et al. and the
      posterior way, described by Jernigan et al. The primary endpoint was the rate of
      success. The secondary endpoints were the related adverse events and the
      difficulty factors. STUDY DESIGN: Prospective, randomized open clinical trial.
      PATIENTS AND METHODS: The study took place in the vital emergency room, the
      operating room and the emergency intensive care unit of Ibn Sina University
      hospital (Rabat, Morocco), between June and September 2010. Hundred and one
      patients needing a central venous catheter were randomized to undergo one of the
      two techniques. We compared: demographics, success rates, number of attempts,
      difficulty factors and adverse events. RESULTS: The success rate was
      significantly higher in the posterior group (96% versus 68%, P < 0.001), with
      fewer attempts (1.3 +/- 0.7 versus 2.1 +/- 1.3; P < 0.001). There were less
      pneumothorax, (0 versus 6%) and more accidental arterial punctures (34 versus
      25.5%) in the posterior group, but the difference wasn't significant. Finally,
      none of the difficulty factors were correlated to the failure rate. CONCLUSION:
      This study shows that the posterior approach in internal jugular venous
      cannulation is more efficient than and as safe as the anterior approach.

PMID- 22465649
TI  - [Refractory thrombotic thrombocytopenic purpura revealing an epiglotis
      neoplasia].
AB  - Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy with
      neurological disorder which incidence is relatively rare. Since the discovery of
      the ADAMTS 13 in 1996 and the changes in the treatment (plasma exchanges and
      rituximab), the prognosis of the TTP has considerably improved. We report the
      case of a 60-year-old man with a refractory TTP. The subsequent discovery of an
      epiglottis neoplasia and its treatment saved the patient.

PMID- 22465650
TI  - [Prospective trial comparing Airtraq and Glidescope techniques for intubation of
      obese patients].
AB  - OBJECTIVES: Videolaryngoscope techniques are more and more in use and tend to
      modify our approach for patients difficult to intubate. We compared two
      techniques, Airtraq and Glidescope with direct laryngoscopy, with special
      emphasis on ease of access to airway (Intubation Difficulty Score - IDS score,
      duration and success of intubation) and the impact on hemodynamic variables among
      patients with a BMI of more than 30. STUDY DESIGN: Prospective study randomised
      with minimisation technique. MATERIAL AND METHODS: Eighty patients have been
      allocated by minimisation to four groups: two groups being intubated with
      Airtraq, each one with a different investigator, and two with Glidescope
      videolaryngoscope technique. Induction of anesthesia was standardly performed
      with total intravenous anesthesia with remifentanil, propofol in TCI mode and
      rocuronium in bolus. Following parameters were recorded : intubation success
      based on intubation time and desaturation level, its duration, its impact on
      hemodynamic variables, IDS score and possible dental lesions. RESULTS: Intubation
      success was 100% for Glidescope and 80.6% for Airtraq (P=0.009). Airtraq allowed
      a better visualisation of the vocal cords (lower Cormack and Lehane score) than
      Glidescope. In contrast, alternative intubation techniques were significantly
      more often used in the Airtraq group. No difference could be detected between
      both systems on hemodynamic parameters. CONCLUSIONS: In obese patients,
      Glidescope allows intubation relatively easily without rescue techniques.

PMID- 22465651
TI  - [Occurrence of severe cardiac alterations in Amanita proxima poisoning: two
      original observations].
AB  - Amanita proxima is one species of white mushroom which can induce poisonings
      called in France "proximien" syndrome. The clinical feature of "proximien"
      syndrome is mainly characterized by early digestive troubles, mild hepatic
      cytolysis and late renal impairment. A cardiac insult has never been reported in
      such a circumstance. The authors describe herein two cases of white mushroom
      poisoning occurred in the Mediterranean French coast with a typical clinical
      feature of "proximien" syndrome plus secondary development of severe cardiac
      alterations. The outcome was good for the two patients thanks to symptomatic
      treatment. The cases reported here suggest that A. proxima have a potential
      severe cardiac toxicity leading to include early and precise cardiac examination
      in the management of patients poisoned by these mushrooms.

PMID- 22465652
TI  - [Neurological complications of the regional anesthesia: analysis of the
      expertises and conclusions of the Regional Commissions for Conciliation and
      Compensation].
AB  - All the files of complications of regional anaesthesias requiring an expertise
      for a Regional Commission for Conciliation and Compensation for medical accidents
      (CRCI) between 2003 and 2008 were analyzed. The objective was to estimate the
      homogeneity of the appointed experts, their opinions and the opinions of the
      CRCI. Querying the database, shared by the National Office for Compensation for
      Medical Accidents (ONIAM) and the CRCI, and identified 40 files corresponding to
      the selection criteria. The expertise carried out involved an anaesthetist in 27
      cases, always registered, either on the national list of the experts in medical
      accidents, or on one list of court-appointed experts. Conversely, in 13 cases, no
      specialist performing himself the technique in question was involved in the
      expertise, and sometimes the expert was registered on any list. Mostly, the non
      specialists do not conclude to medical malpractice. This was not the case in a
      single file, where the anaesthetist sought and obtained the addition of an
      anaesthetist in a new expertise, which concluded differently. Damages assessed
      were highly variable, but the given evidence provided to understand why. The CRCI
      have generally followed the opinions of the experts, except in a few cases where
      the evidence allowed a different opinion without requiring a new expertise. In
      conclusion, the abnormalities in the appointment of experts do not seem to have
      had consequences in terms of damage assessment, but may alter the balance between
      causes faulty and not faulty, in favour of the latter.

PMID- 22465653
TI  - [Critical appraisal of organ procurement under Maastricht 3 condition].
AB  - The ethics committee of the French Society of Anesthesia and Intensive Care
      (Sfar) has been requested by the French Biomedical Agency to consider the issue
      of organ donation in patients after a decision of withdrawing life supporting
      therapies has been taken. This category of organ donation is performed in the
      USA, Canada, United Kingdom, the Netherlands and Belgium. The three former
      countries have published recommendations, which formalize procedures and
      operations. The Sfar ethics committee has considered this issue and envisioned
      the different aspects of the whole process. Consequently, it sounds a note of
      caution regarding the applicability of this type of organ procurement in
      unselected patient following a decision to withdraw life supporting therapies.
      According to the French regulation concerning organ procurement in brain dead
      patients, the committee stresses the need to restrict this specific way of
      procurement to severely brain injured patients, once confirmatory investigations
      predicting a catastrophic prognosis have been performed. It suggests that the
      nature of the confirmatory investigation required should be formalized by the
      French Biomedical Agency on behalf of the French parliamentarians. This should
      help preserving population trust regarding organ procurement and provide a
      framework to medical decision. This text has been endorsed by the Sfar.

PMID- 22465654
TI  - [Comments on the principle of organ procurement following the withdrawal of life
      supporting therapies].

PMID- 22465655
TI  - Effects of milrinone on left ventricular cardiac function during cooling in an
      intact animal model.
AB  - INTRODUCTION: Due to adverse effects of beta-receptor agonists reported when
      applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a
      PDE3 inhibitor which mode of action is deprived the sarcolemmal beta-receptor-G
      protein-PKA system, was tested during cooling to 15  degrees C. METHODS: Sprague
      Dawley rats were instrumented to measure left ventricular (LV) pressure-volume
      changes using a Millar pressure-volume conductance catheter. Core temperature was
      reduced from 37 to 15  degrees C (60 min) using internal and external heat
      exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions
      for 30 min at 37  degrees C and during cooling. RESULTS: In normothermic controls
      continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke
      volume (SV) significantly. Significant differences in cardiac functional
      variables between the milrinone group and the saline control group during cooling
      to 15  degrees C were found: Compared to saline treated animals throughout
      cooling from 33 to 15  degrees CSV was significantly elevated in milrinone
      animals, the index of LV isovolumic relaxation, Tau, was significantly better
      preserved, and both HR and CO were significantly higher from 33 to 24  degrees C.
      Likewise, during cooling between 33 and 28  degrees C also LVdP/dt(max) was
      significantly higher in the milrinone group. CONCLUSIONS: Milrinone preserved LV
      systolic and diastolic function at a significantly higher level than in saline
      controls during cooling to 15  degrees C. In essential contrast to our previous
      results when using beta-receptor agonists during hypothermia, the present
      experiment demonstrates the positive inotropic effects of milrinone on LV cardiac
      function during cooling to 15  degrees C.

PMID- 22465656
TI  - Preliminary report of novel technique for cryopreservation--vacuum-assisted
      cryoprotectant infiltration.
AB  - To date, cryopreservation of large soft tissues has not been successfully
      achieved because of limitation of cryoprotective agent (CPA) infiltration into
      the tissue. This study aimed to investigate the effects of a vacuum on the tissue
      infiltration of a CPA. An instant pickle-maker was modified for use as a vacuum
      apparatus, and glycerol was selected as the CPA. Twenty-six rats were used, and
      their thighs were divided into three treatment groups. Group 1: fresh control;
      Group 2: cryopreserved control, i.e., immersed in the CPA for 1h under
      atmospheric pressure and cryopreserved; Group 3: vacuum-assisted CPA
      infiltration, i.e., immersed in the CPA under negative pressure (20, 40 and 60
      cmHg, for durations of 10, 20 and 30 min at each) and cryopreserved. The Groups 2
      and 3 specimens were thawed after 3 weeks of cryopreservation at -80  degrees C
      and histologically examined, in comparison with Group 1. Skin: in Groups 2 and 3,
      the skin was well preserved. Muscle: in Group 2, both extracellular and
      intracellular ice crystal formation was widely distributed throughout the muscle
      tissue. In Group 3, under an adequate vacuum, the muscle tissue was well
      preserved, with no ice crystal formation. However, when the treatment was
      conducted under excessive vacuum conditions, the muscle tissue showed focal
      necrosis. Blood vessels: in Group 3, both the arteries and veins were well
      preserved up to the tunica intima. The method described in this paper may be a
      useful technique for achieving cryopreservation of large soft tissues.

PMID- 22465657
TI  - Does the cryogenic freezing process cause shorter telomeres?
AB  - We have observed evidence of increased telomere shortening in short-term T
      lymphocyte cultures following freezing and thawing of the original inoculum
      obtained by ficoll-paque gradient centrifugation, compared to T-lymphocytes that
      were cultured immediately without freezing and thawing from the same blood sample
      from 3 female and 3 male adults. Because freezing may have similar effects on
      other cell types, and because telomere shortening may only manifest its effects
      after many years or decades, we suggest there is a pressing need for evaluation
      of the effects of freezing on any cells envisioned for clinical applications,
      including embryo implantation.

PMID- 22465658
TI  - A systematic study on lyophilization process of polymersomes for long-term
      storage using doxorubicin-loaded (PEG)3-PLA nanopolymersomes.
AB  - This study is focused on lyophilization process, physicochemical characterization
      and long-term storage stability studies of lyophilized doxorubicin-loaded
      (PEG)(3)-PLA nanopolymersomes. Nanopolymersomes were prepared by
      nanoprecipitation method using (PEG)(3)-PLA copolymer and lyophilized in the
      presence of different lyoprotectants and evaluated for physicochemical
      properties. The lyophilized product was studied for long-term stability at 2-8 
      degrees C, 25  degrees C/65% RH and 40  degrees C/75% RH over predetermined
      periods and evaluated for changes in physicochemical properties. In the absence
      of lyoprotectants, product was collapsed with no cake formation. In the presence
      of inulin, mannitol, gelatin, polyvinyl alcohol and glycine, nanopolymersome
      formulations demonstrated an intact cake occupying same volume as original frozen
      mass. The residual moisture content was below 2.5% w/w. The time of
      reconstitution was instantaneous following addition of water without any manual
      shaking. However, inulin found to be superior to the rest of lyoprotectants for
      overall lyophilizate physicochemical properties. Drug loaded nanopolymersome were
      physically stable and no effect was observed in terms of physicochemical
      properties following one year at 2-8  degrees C. In conclusion, the results
      suggest that doxorubicin loaded nanopolymersomes could be lyophilized using
      inulin 5% w/v without losing its physicochemical properties and can be stored at
      2-8  degrees C with a provisional shelf life of more than a year.

PMID- 22465659
TI  - Differential state-dependent modification of inactivation-deficient Nav1.6 sodium
      channels by the pyrethroid insecticides S-bioallethrin, tefluthrin and
      deltamethrin.
AB  - Pyrethroid insecticides disrupt nerve function by modifying the gating kinetics
      of transitions between the conducting and nonconducting states of voltage-gated
      sodium channels. Pyrethroids modify rat Na(v)1.6+beta1+beta2 channels expressed
      in Xenopus oocytes in both the resting state and in one or more states that
      require channel activation by repeated depolarization. The state dependence of
      modification depends on the pyrethroid examined: deltamethrin modification
      requires repeated channel activation, tefluthrin modification is significantly
      enhanced by repeated channel activation, and S-bioallethrin modification is
      unaffected by repeated activation. Use-dependent modification by deltamethrin and
      tefluthrin implies that these compounds bind preferentially to open channels. We
      constructed the rat Na(v)1.6Q3 cDNA, which contained the IFM/QQQ mutation in the
      inactivation gate domain that prevents fast inactivation and results in a
      persistently open channel. We expressed Na(v)1.6Q3+beta1+beta2 sodium channels in
      Xenopus oocytes and assessed the modification of open channels by pyrethroids by
      determining the effect of depolarizing pulse length on the normalized conductance
      of the pyrethroid-induced sodium tail current. Deltamethrin caused little
      modification of Na(v)1.6Q3 following short (10ms) depolarizations, but prolonged
      depolarizations (up to 150ms) caused a progressive increase in channel
      modification measured as an increase in the conductance of the pyrethroid-induced
      sodium tail current. Modification by tefluthrin was clearly detectable following
      short depolarizations and was increased by long depolarizations. By contrast
      modification by S-bioallethrin following short depolarizations was not altered by
      prolonged depolarization. These studies provide direct evidence for the
      preferential binding of deltamethrin and tefluthrin (but not S-bioallethrin) to
      Na(v)1.6Q3 channels in the open state and imply that the pyrethroid receptor of
      resting and open channels occupies different conformations that exhibit distinct
      structure-activity relationships.

PMID- 22465660
TI  - Intracerebroventricular administration of neuronostatin delays gastric emptying
      and gastrointestinal transit in mice.
AB  - Neuronostatin is a 13-amino acid amidated peptide widely distributed in various
      organs including gastrointestinal tract. However, the effect of neuronostatin on
      gastrointestinal motility has not been well characterized. In the present work,
      effects of central administration of neuronostatin on gastric emptying and
      gastrointestinal transit were investigated. The results indicated that
      intracerebroventricular (i.c.v.) administration of neuronostatin (1, 5, 10 or
      20nmol/mouse) delayed gastric emptying and gastrointestinal transit in a dose
      related manner in mice. The effects were significantly reversed by melanocortin
      3/4 receptor antagonist SHU9119 or classical opioid receptor antagonist naloxone,
      suggesting that the central melanocortin system and opioid system may be involved
      in the gastrointestinal effects elicited by i.c.v. administration of
      neuronostatin. In addition, we found that C-terminal amidation modification of
      neuronostatin is essential to exert its gastrointestinal effects. These results
      indicated that neuronostatin may play an important role in regulating
      gastrointestinal function.

PMID- 22465661
TI  - Identification of orexins and cognate receptors in the lacrimal gland of sheep.
AB  - The aim of the present work was to study, by means of immunohistochemical and RT
      PCR techniques, the presence and distribution of immunopositivity for orexin A
      and B (OXA and OXB) and orexin type 1 and 2 receptors (OX(1)R and OX(2)R) in the
      lacrimal gland of sheep as well as the gene expressions for prepro-orexin (PPOX)
      and cognate receptors. In serial sections, positive staining for OXA and OXB were
      localized in the same nervous fibers within the connective tissue septa. Positive
      staining for OX(1)R was evidenced in the wall of small arteries while that for
      OX(2)R was observed in the secretory portion of the acinar gland cells with a
      characteristic localization in the apical cytoplasm. RT-PCR analysis showed the
      presence of transcripts for PPOX, OX(1)R and OX(2)R in the sheep lacrimal gland;
      the gene expression of OX(1)R was two-fold greater (p<0.01) than that of OX(2)R.
      Taken together the present findings raise intriguing questions on the potential
      role of the orexinergic system in the regulation of lacrimal gland functions that
      require further investigations.

PMID- 22465662
TI  - Ceramide kinase deficiency improves diet-induced obesity and insulin resistance.
AB  - Ceramide kinase (CERK) is an enzyme that phosphorylates ceramide to produce
      ceramide 1-phosphate. Recently, evidence has emerged that CERK has a role in
      inflammatory signaling of immune cells. Since obesity is accompanied by chronic,
      low-grade inflammation, we examined whether CERK might be involved using CERK
      null mice. We determined that CERK deficiency suppresses diet-induced increases
      in body weight, and improves glucose intolerance. Furthermore, we demonstrated
      that CERK deficiency attenuates MCP-1/CCR2 signaling in macrophages infiltrating
      the adipose tissue, resulting in the suppression of inflammation in adipocytes,
      which might otherwise lead to obesity and diabetes.

PMID- 22465663
TI  - MiR-483-5p suppresses the proliferation of glioma cells via directly targeting
      ERK1.
AB  - MicroRNAs (miRNAs) exhibit tumor-specific expression signatures and play crucial
      roles in tumorigenesis by targeting oncogenes. Here, through analyzing the miRNA
      array profiles of human glioblastoma tissues and the adjacent normal brain
      tissues, we found miR-483-5p was significantly down-regulated in gliomas, which
      was confirmed in both human glioma specimens and cell lines. The overexpression
      of miR-483-5p suppressed glioma cell proliferation and induced a G0/G1 arrest. In
      contrast, miR-483-5p inhibition promoted cell proliferation. Furthermore, by a
      dual-luciferase reporter assay and expression analysis, we identified
      extracellular signal-regulated kinase 1 (ERK1) as a direct target of miR-483-5p.
      ERK1 knockdown can block cell proliferation induced by miR-483-5p inhibition.
      Thus, our findings provide the first evidence that miR-483-5p can serve as a
      tumor suppressor in gliomas.

PMID- 22465664
TI  - Expression, purification and assembly of soluble multimeric MHC class II
      invariant chain complexes.
AB  - Major histocompatibility class (MHC) II molecules are essential for running
      adaptive immune response. They are produced in the ER and targeted to late
      endosomes with the help of invariant chain (Ii) trimers. Ii trimerization may be
      induced by the Ii TM domain. To enable mechanistic and structural studies of MHC
      class II-Ii assembly, soluble forms of the complexes were expressed. We show that
      Ii trimerizes in the absence of the transmembrane part, prior to binding of
      alpha/beta chains. The biochemical analysis supports the suggestion that the MHC
      class II-Ii complexes are not necessarily trimers of trimers, but that the Ii
      trimer can also be occupied by one or two MHC class II complexes.

PMID- 22465665
TI  - Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in
      regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer
      cells.
AB  - The mechanisms underlying ovarian cancer cell resistance to cisplatin (CDDP) are
      not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis
      and drug resistance. In this paper, we utilized microRNA array and real-time PCR
      to show that miR-93 is significantly up-regulated in cisplatin-resistant ovarian
      cancer cells. In vitro assays show that over-expression and knock-down of miR-93
      regulate apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian
      cells. Furthermore, we found that miR-93 can directly target PTEN, and
      participates in the regulation of the AKT signaling pathway. MiR-93 inversely
      correlates with PTEN expression in CDDP-resistant and sensitive human ovarian
      cancer tissues. These results may have implications for therapeutic strategies
      aiming to overcome ovarian cancer cell resistance to cisplatin.

PMID- 22465666
TI  - Identification of a novel protein kinase Cdelta-Smac complex that dissociates
      during paclitaxel-induced cell death.
AB  - Protein kinase C (PKC) delta is a regulator of apoptosis with both pro- and anti
      apoptotic effects. The mechanistic basis for the discrepant effects is not
      completely understood. Here we show that Smac interacts with PKCdelta. The
      interaction depends on the N-terminus of Smac and is disrupted upon treatment
      with paclitaxel. This is associated with release of Smac into the cytosol.
      Activation of PKCdelta rescues the interaction during paclitaxel exposure and
      suppresses the paclitaxel-mediated cell death. However, under these conditions
      the complex is mainly found in the cytosol suggesting that cytosolic Smac can be
      bound by PKCdelta when PKC is activated. The data unravel a previously
      unrecognized interaction and suggest that PKCdelta by associating with Smac may
      prevent its apoptotic effects.

PMID- 22465667
TI  - GLI3 constrains digit number by controlling both progenitor proliferation and BMP
      dependent exit to chondrogenesis.
AB  - Inactivation of Gli3, a key component of Hedgehog signaling in vertebrates,
      results in formation of additional digits (polydactyly) during limb bud
      development. The analysis of mouse embryos constitutively lacking Gli3 has
      revealed the essential GLI3 functions in specifying the anteroposterior (AP) limb
      axis and digit identities. We conditionally inactivated Gli3 during mouse hand
      plate development, which uncoupled the resulting preaxial polydactyly from known
      GLI3 functions in establishing AP and digit identities. Our analysis revealed
      that GLI3 directly restricts the expression of regulators of the G(1)-S cell
      cycle transition such as Cdk6 and constrains S phase entry of digit progenitors
      in the anterior hand plate. Furthermore, GLI3 promotes the exit of proliferating
      progenitors toward BMP-dependent chondrogenic differentiation by spatiotemporally
      restricting and terminating the expression of the BMP antagonist Gremlin1. Thus,
      Gli3 is a negative regulator of the proliferative expansion of digit progenitors
      and acts as a gatekeeper for the exit to chondrogenic differentiation.

PMID- 22465668
TI  - Kinesin-1 prevents capture of the oocyte meiotic spindle by the sperm aster.
AB  - Centrioles are lost during oogenesis and inherited from the sperm at
      fertilization. In the zygote, the centrioles recruit pericentriolar proteins from
      the egg to form a mature centrosome that nucleates a sperm aster. The sperm aster
      then captures the female pronucleus to join the maternal and paternal genomes.
      Because fertilization occurs before completion of female meiosis, some mechanism
      must prevent capture of the meiotic spindle by the sperm aster. Here we show that
      in wild-type Caenorhabditis elegans zygotes, maternal pericentriolar proteins are
      not recruited to the sperm centrioles until after completion of meiosis.
      Depletion of kinesin-1 heavy chain or its binding partner resulted in premature
      centrosome maturation during meiosis and growth of a sperm aster that could
      capture the oocyte meiotic spindle. Kinesin prevents recruitment of
      pericentriolar proteins by coating the sperm DNA and centrioles and thus prevents
      triploidy by a nonmotor mechanism.

PMID- 22465669
TI  - Awareness of and behaviors related to child-to-mother transmission of
      cytomegalovirus.
AB  - OBJECTIVE: Congenital cytomegalovirus (CMV) infection is a common cause of
      hearing loss and intellectual disability. We assessed CMV knowledge and the
      frequency of women's behaviors that may enable CMV transmission to inform
      strategies for communicating prevention messages to women. METHODS: We analyzed
      survey responses from 4184 participants (2181 women, 2003 men) in the 2010
      HealthStyles survey, a national mail survey designed to be similar to the United
      States population. RESULTS: Only 7% of men and 13% of women had heard of
      congenital CMV. Women with children under age 19 (n=918) practiced the following
      risk behaviors at least once per week while their youngest child was still in
      diapers: kissing on the lips (69%), sharing utensils (42%), sharing cups (37%),
      and sharing food (62%). Women practiced protective, hand cleansing behaviors most
      of the time or always after: changing a dirty diaper (95%), changing a wet diaper
      (85%), or wiping the child's nose (65%), but less commonly after handling the
      child's toys (26%). CONCLUSIONS: Few women are aware of CMV and most regularly
      practice behaviors that may place them at risk when interacting with young
      children. Women should be informed of practices that can reduce their risk of CMV
      infection during pregnancy.

PMID- 22465670
TI  - Characteristics associated with the uptake of influenza vaccination among adults
      in the United States.
AB  - OBJECTIVE: Existing data suggest that influenza vaccination rates among adults in
      the United States fall far short of the Healthy People 2010 goals and the updated
      Healthy People 2020 targets. We identified characteristics associated with
      influenza vaccination that might inform strategies for increasing coverage.
      METHODS: We used data from the 2009 Behavioral Risk Factor Surveillance System to
      estimate adjusted prevalence ratios for receiving the influenza vaccine in the
      past 12 months. RESULTS: Among 134,101 adults aged >=65 years, the influenza
      vaccination coverage level was 68.9%. Among 286,867 younger adults aged 18-64
      years, coverage was markedly lower: 31.8%. Having health care coverage was the
      strongest predictor of vaccination in both age groups, after accounting for other
      sociodemographic characteristics, health behaviors, and health status. Those
      reporting older age, white race, higher education, non-smoking status, being
      physically active, or having poor physical health or a personal history of
      various chronic conditions were also more likely to report having received the
      influenza vaccine. CONCLUSION: Our results show clearly that vaccine uptake in
      the United States is related to social position as well as other health
      behaviors. These findings call for renewed attention to vaccination strategies to
      meet the updated Healthy People 2020 goals.

PMID- 22465671
TI  - Healthy lifestyle and obesity among elderly with cardiovascular risks: authors'
      response.

PMID- 22465673
TI  - Functional alterations in endothelial NO, PGI2 and EDHF pathways in aorta in
      ApoE/LDLR-/- mice.
AB  - Adequate endothelial production of nitric oxide (NO), endothelium-derived
      hyperpolarizing factor (EDHF), and prostacyclin (PGI2) is critical to the
      maintenance of vascular homeostasis. However, it is not clear whether alterations
      in each of these vasodilatory pathways contribute to the impaired endothelial
      function in murine atherosclerosis. In the present study, we analyze the
      alterations in NO-, EDHF- and PGI2-dependent endothelial function in the thoracic
      aorta in relation to the development of atherosclerotic plaques in apoE/LDLR-/-
      mice. We found that in the aorta of 2-month-old apoE/LDLR-/- mice there was no
      lipid deposition, subendothelial macrophage accumulation; and matrix
      metalloproteinase (MMP) activity was low, consistent with the absence of
      atherosclerotic plaques. Interestingly, at this stage the endothelium was already
      activated and hypertrophic as evidenced by electron microscopy, while
      acetylcholine-induced NO-dependent relaxation in the thoracic aorta was impaired,
      with concomitant upregulation of cyclooxygenase-2 (COX-2)/PGI2 and EDHF
      (epoxyeicosatrienoic acids, EETs) pathways. In the aorta of 3-6-month-old
      apoE/LDLR-/- mice, lipid deposition, macrophage accumulation and MMP activity in
      the intima were gradually increased, while impairment of NO-dependent function
      and compensatory upregulation of COX-2/PGI2 and EDHF pathways were more
      accentuated. These results suggest that impairment of NO-dependent relaxation
      precedes the development of atherosclerosis in the aorta and early upregulation
      of COX-2/PGI2 and EDHF pathways may compensate for the loss of the biological
      activity of NO.

PMID- 22465672
TI  - Role of arginine 293 and glutamine 288 in communication between catalytic and
      allosteric sites in yeast ribonucleotide reductase.
AB  - Ribonucleotide reductases (RRs) catalyze the rate-limiting step of de novo
      deoxynucleotide (dNTP) synthesis. Eukaryotic RRs consist of two proteins, RR1
      (alpha) that contains the catalytic site and RR2 (beta) that houses a diferric
      tyrosyl radical essential for ribonucleoside diphosphate reduction. Biochemical
      analysis has been combined with isothermal titration calorimetry (ITC), X-ray
      crystallography and yeast genetics to elucidate the roles of two loop 2 mutations
      R293A and Q288A in Saccharomyces cerevisiae RR1 (ScRR1). These mutations, R293A
      and Q288A, cause lethality and severe S phase defects, respectively, in cells
      that use ScRR1 as the sole source of RR1 activity. Compared to the wild-type
      enzyme activity, R293A and Q288A mutants show 4% and 15%, respectively, for ADP
      reduction, whereas they are 20% and 23%, respectively, for CDP reduction. ITC
      data showed that R293A ScRR1 is unable to bind ADP and binds CDP with 2-fold
      lower affinity compared to wild-type ScRR1. With the Q288A ScRR1 mutant, there is
      a 6-fold loss of affinity for ADP binding and a 2-fold loss of affinity for CDP
      compared to the wild type. X-ray structures of R293A ScRR1 complexed with dGTP
      and AMPPNP-CDP [AMPPNP, adenosine 5-(beta,gamma-imido)triphosphate tetralithium
      salt] reveal that ADP is not bound at the catalytic site, and CDP binds farther
      from the catalytic site compared to wild type. Our in vivo functional analyses
      demonstrated that R293A cannot support mitotic growth, whereas Q288A can, albeit
      with a severe S phase defect. Taken together, our structure, activity, ITC and in
      vivo data reveal that the arginine 293 and glutamine 288 residues of ScRR1 are
      crucial in facilitating ADP and CDP substrate selection.

PMID- 22465674
TI  - Structure-activity relationships of siRNA carriers based on sequence-defined
      oligo (ethane amino) amides.
AB  - Sequence defined oligo (ethane amino) amides produced by solid-phase supported
      synthesis using different building blocks and molecular shapes were tested for
      structure-activity relationships in siRNA delivery. Efficient reporter gene
      knockdown was obtained in a variety of cell lines using either branched three
      armed structures, or lipid-modified structures with i-shape, T-shape, U-shape
      configuration. For the majority of structures (apart from U-shapes), the presence
      of 2 or 3 cysteines was strictly required for polyplex stabilization and
      silencing activity. Although all four building blocks contain the ethylenediamine
      proton sponge motif, only oligomers assembled with the tetraethylenepentamine
      based amino acids (Stp, Gtp, Ptp) but not with the triethylenetetramine based
      amino acid (Gtt) were able to mediate efficient gene silencing. For the
      lipopolymeric structures, out of the tested saturated (from C4 to C18) and
      unsaturated (C18) fatty acid moieties, two proximate oleic acids or linolic acids
      provided the oligomers with the best gene silencing activity and also pH specific
      lytic activity at pH 5.5, presumably facilitating endosomal escape of the
      polyplexes. Evaluation of oligomer chain length revealed a minimal number of at
      least two oligo (ethane amino) building blocks per oligomer arm as necessary for
      the vast majority of structures, but only marginal changes were found with higher
      numbers (structures with up to 60 ethane amino nitrogens were evaluated). Two
      promising carriers (T-shape 49, i-shape 229) were also evaluated for EG5 siRNA
      delivery. This resulted in tumor cell cycle arrest, and appearance of mitotic
      monoastral spindles both in vitro and in vivo upon systemic delivery. Repeated
      intratumoral treatment with EG5 siRNA polyplexes significantly reduced Neuro2A
      eGFPLuc tumor growth in a siRNA-specific manner.

PMID- 22465675
TI  - siRNA and pharmacological inhibition of endocytic pathways to characterize the
      differential role of macropinocytosis and the actin cytoskeleton on cellular
      uptake of dextran and cationic cell penetrating peptides octaarginine (R8) and
      HIV-Tat.
AB  - Cell penetrating peptides (CPPs) have been extensively studied as vectors for
      cellular delivery of therapeutic macromolecules. It is widely accepted that they
      can enter cells directly across the plasma membrane but also gain access through
      endocytic pathways that are yet to be fully defined. Here we developed siRNA
      methods in epithelial cell lines, HeLa and A431, to inhibit endocytic pathways
      regulated by clathrin heavy chain, flotillin-1, caveolin-1, dynamin-2 and Pak-1.
      In each case, functional uptake assays were developed to characterize the
      requirement for these proteins, and the pathways they regulate, in the
      internalisation of defined endocytic probes and also the CPPs octaarginine and
      HIV-Tat. Peptide uptake was only inhibited in A431 cells depleted of the
      macropinocytosis regulator Pak-1, but experimental variables including choice of
      cell line, pharmacological inhibitor, macropinocytic probe and serum starvation
      significantly influence our ability to assess and assign this pathway as an
      important route for CPP uptake. Actin disruption with Cytochalasin D inhibited
      peptide entry in both cell lines but the effects of this agent on dextran uptake
      was cell line dependent, reducing uptake in HeLa cells and increasing uptake in
      A431 cells. This was further supported in experiments inducing actin
      stabilisation by Jasplakinolide, emphasising that the actin cytoskeleton can both
      promote and hinder endocytosis. Overall the data identify important aspects
      regarding the comparative mechanisms of CPP uptake and macropinocytosis, and
      accentuate the significant methodological challenges of studying this pathway as
      an endocytic portal and an entry route for drug delivery vectors.

PMID- 22465677
TI  - How acoustic cavitation can improve adhesion.
AB  - In general, ultrasound is commonly used at low power level for non-destructive
      testing (NDT) and detection of delaminations in adhesive bonded structures. The
      present paper instead presents an approach where power ultrasound is used to
      improve interface formation prior to the bonding process and to ensure the
      quality of adhesive bonds by using acoustic cavitation in the liquid adhesive.
      Results from high-speed videos, rheological and thermal measurements and
      destructive testing of adhesive bonds with contaminated surfaces are presented
      and discussed. Power ultrasound can be used in general to improve adhesion and
      significantly to improve contamination tolerance and robustness of adhesive
      bonding processes.

PMID- 22465676
TI  - Two-layered injectable self-assembling peptide scaffold hydrogels for long-term
      sustained release of human antibodies.
AB  - The release kinetics for human immunoglobulin (IgG) through the permeable
      structure of nanofiber scaffold hydrogels consisting of the ac-(RADA)(4)-CONH(2)
      and ac-(KLDL)(3)-CONH(2) self-assembling peptides were studied during a period of
      3 months. Self assembling peptides are a class of stimuli-responsive materials
      which undergo sol-gel transition in the presence of an electrolyte solution such
      as biological fluids and salts. IgG diffusivities decreased with increasing
      hydrogel nanofiber density providing a means to control the release kinetics. Two
      layered hydrogel structures were created consisting of concentric spheres of ac
      (RADA)(4)-CONH(2) core and ac-(KLDL)(3)-CONH(2) shell and the antibody diffusion
      profile was determined through the 'onion-like' architecture. Secondary and
      tertiary structure analyses as well as biological assays using single molecule
      analyses and quartz crystal microbalance of the released IgG showed that
      encapsulation and release did not affect the conformation of the antibody and the
      biological activity even after 3 months inside the hydrogel. The functionality of
      polyclonal human IgG to the phosphocholine antigen was determined and showed that
      IgG encapsulation and release did not affect the antibody binding efficacy to the
      antigen. Our experimental protocol allows for 100% IgG loading efficiency inside
      the hydrogel while the maximum amount of antibody loading depends solely on the
      solubility of the antibody in water because the peptide hydrogel consists of
      water up to 99.5%. Our results show that this fully biocompatible and injectable
      peptide hydrogel system may be used for controlled release applications as a
      carrier for therapeutic antibodies.

PMID- 22465678
TI  - Serial section registration of axonal confocal microscopy datasets for long-range
      neural circuit reconstruction.
AB  - In the context of long-range digital neural circuit reconstruction, this paper
      investigates an approach for registering axons across histological serial
      sections. Tracing distinctly labeled axons over large distances allows
      neuroscientists to study very explicit relationships between the brain's complex
      interconnects and, for example, diseases or aberrant development. Large scale
      histological analysis requires, however, that the tissue be cut into sections. In
      immunohistochemical studies thin sections are easily distorted due to the
      cutting, preparation, and slide mounting processes. In this work we target the
      registration of thin serial sections containing axons. Sections are first traced
      to extract axon centerlines, and these traces are used to define registration
      landmarks where they intersect section boundaries. The trace data also provides
      distinguishing information regarding an axon's size and orientation within a
      section. We propose the use of these features when pairing axons across sections
      in addition to utilizing the spatial relationships among the landmarks. The
      global rotation and translation of an unregistered section are accounted for
      using a random sample consensus (RANSAC) based technique. An iterative nonrigid
      refinement process using B-spline warping is then used to reconnect axons and
      produce the sought after connectivity information.

PMID- 22465679
TI  - Distal hypoxic stroke: a new mouse model of stroke with high throughput, low
      variability and a quantifiable functional deficit.
AB  - C57BL/6J are the most commonly used strain of mouse for stroke experiments but
      vascular anatomy of the Circle of Willis within this strain is extremely variable
      and the cortex has extensive collateralization. This causes large variability in
      stroke models that target the middle cerebral artery proximally and confers
      resistance to ischemia in those that target it distally. We tested the hypothesis
      that by combining distal middle cerebral artery occlusion with 1h of hypoxia, we
      could generate a large lesion that causes a behavioral deficit with low
      variability. We found that this new distal hypoxic (DH) model of stroke generates
      a lesion with a volume of 25% of the ipsilateral hemisphere, extends to the motor
      cortex and causes a behavioral deficit. It also has a very clear border,
      exceptionally low variability, and can be performed by a single surgeon on up to
      30 animals a day. Moreover, survivability is 100% in young adult animals, the
      model can be performed on old animals, and therapeutic intervention can reduce
      infarct volume. Therefore DH stroke is an excellent complement to existing stroke
      models and could be used for preclinical studies in C57BL/6J mice.

PMID- 22465680
TI  - Neurotrophins and their role in the cochlea.
AB  - Spiral ganglion cell (SGC) degeneration following hair cell loss can be prevented
      by administration of exogenous neurotrophic factors. Many of these neurotrophic
      factors, in particular the neurotrophins brain-derived neurotrophic factor (BDNF)
      and neurotrophin-3 (NT-3), have been described to be involved in the development
      of the rodent cochlea. While expression of most of the neurotrophins has
      decreased to below detectable levels during adulthood (only NT-3 remains highly
      expressed), their respective receptors remain present in SGCs. Indeed much less
      is known about the function of neurotrophins in the mature cochlea. Such
      knowledge is crucial in the search for tools to improve SGC survival following
      cochlear implantation. In this review, we will critically regard the current
      experimental findings of neurotrophic treatment of the SGCs in the perspective of
      fundamental cellular mechanisms underlying neurotrophin signaling. We conclude
      that, in order to fully apprehend the effects of neurotrophic treatment of
      degenerating SGCs and in order to consider clinical application of neurotrophins,
      future research should focus (a) on characterizing the expression pattern of
      neurotrophins in the cochlea after deafening, (b) on more detailed
      characterization of functional and morphological changes of SGCs associated with
      both deafening and neurotrophic treatment and (c) on the possible self-supporting
      state of SGCs after cessation of short-term neurotrophic treatment.

PMID- 22465681
TI  - Factors affecting predicted speech intelligibility with cochlear implants in an
      auditory model for electrical stimulation.
AB  - A model of the auditory response to stimulation with cochlear implants (CIs) was
      used to predict speech intelligibility in electric hearing. The model consists of
      an auditory nerve cell population that generates delta pulses as action
      potentials in response to temporal and spatial excitation with a simulated CI
      signal processing strategy. The auditory nerve cells are modeled with a leaky
      integrate-and-fire model with membrane noise. Refractory behavior is introduced
      by raising the threshold potential with an exponentially decreasing function.
      Furthermore, the action potentials are delayed to account for latency and jitter.
      The action potentials are further processed by a central model stage, which
      includes spatial and temporal integration, resulting in an internal
      representation of the sound presented. Multiplicative noise is included in the
      internal representations to limit resolution. Internal representations of
      complete word sets for a sentence intelligibility test were computed and
      classified using a Dynamic-Time-Warping classifier to quantify information
      content and to estimate speech intelligibility. The number of auditory nerve
      cells, the spatial spread of the electrodes' electric field, and the internal
      noise intensity were found to have a major impact on the modeled speech
      intelligibility, whereas the influence of refractory behavior, membrane noise,
      and latency and jitter was minor.

PMID- 22465683
TI  - Synthetic biology: emerging methodologies to catalyze the metabolic engineering
      design cycle.

PMID- 22465682
TI  - Lipopolysaccharide inhibits ghrelin-excited neurons of the arcuate nucleus and
      reduces food intake via central nitric oxide signaling.
AB  - Lipopolysaccharide (LPS) induces anorexia and expression of inducible nitric
      oxide synthase (iNOS) in the hypothalamic arcuate nucleus (Arc). Peripheral
      administration of the iNOS inhibitor 1400 W counteracts the anorectic effects of
      LPS. Here we investigated the role of central NO signaling in LPS anorexia. In
      electrophysiological studies we tested whether 1400 W counteracts the iNOS
      dependent inhibition of Arc neurons triggered by in vivo or in vitro stimulation
      with LPS. We used the hormone ghrelin as a functional reference stimulus because
      ghrelin is known to activate orexigenic Arc neurons. Further, we investigated
      whether in vitro LPS stimulation induces an iNOS-mediated formation of the second
      messenger cGMP. Since the STAT1 pathway contributes to the regulation of iNOS
      expression we investigated whether LPS treatment induces STAT1 phosphorylation in
      the Arc. Finally we tested the effect of intracerebroventricular injection of
      1400 W on LPS-induced anorexia. Superfusion with 1400 W (10(-4) M) increased
      neuronal activity in 37% of neurons in Arc slices from LPS treated (100 MUg/kg
      ip) but not from saline treated rats. Similarly, 1400 W excited 45% of Arc
      neurons after in vitro stimulation with LPS (100 ng/ml). In both approaches, a
      considerable percentage of 1400 W sensitive neurons were excited by ghrelin (10(
      8)M; 50% and 75%, respectively). In vitro stimulation with LPS induced cGMP
      formation in the Arc, which was blocked by co-incubation with 1400 W. LPS
      treatment elicited a pSTAT1 response in the Arc of mice. Central 1400 W injection
      (4 MUg/rat) attenuated LPS-induced anorexia and counteracted the LPS-dependent
      decrease in respiratory quotient and energy expenditure. In conclusion, the
      current findings substantiate a role of central iNOS dependent NO formation in
      LPS-induced effects on eating and energy homeostasis. A pharmacological blockade
      of NO formation might be a therapeutic approach to ameliorate disease-related
      anorexia.

PMID- 22465684
TI  - Application of accelerated solvent extraction in the analysis of organic
      contaminants, bioactive and nutritional compounds in food and feed.
AB  - Accelerated solvent extraction (ASE) has become a popular green extraction
      technology for different classes of organic contaminants present in numerous
      kinds of food and feed for food safety. The parameters affecting ASE efficiency
      and application advancement of ASE in the analysis of organic contaminants,
      natural toxins compounds as well as bioactive and nutritional compounds in animal
      origin food, plant origin food and animal feed are reviewed in detail. ASE is a
      fully automated and reliable extraction technique with many advantages over
      traditional extraction techniques, so it could be especially useful for routine
      analyses of pollutants in food and feed.

PMID- 22465685
TI  - Modeling of dispersion in a polymeric chromatographic monolith.
AB  - Dispersion in a commercial polymeric monolith was simulated on a sample geometry
      obtained by direct imaging using high-resolution electron microscopy. A
      parallelized random walk algorithm, implemented using a velocity field obtained
      previously by the lattice-Boltzmann method, was used to model mass transfer. Both
      point particles and probes of finite size were studied. Dispersion simulations
      with point particles using periodic boundaries resulted in plate heights that
      varied almost linearly with flow rate, at odds with the weaker dependence
      suggested by experimental observations and predicted by theory. This discrepancy
      resulted from the combined effect of the artificial symmetry in the velocity
      field and the periodic boundaries implemented to emulate macroscopic column
      lengths. Eliminating periodicity and simulating a single block length instead
      resulted in a functional dependence of plate heights on flow rate more in accord
      with experimental trends and theoretical predictions for random media. The lower
      values of the simulated plate heights than experimental ones are attributed in
      part to the presence of walls in real systems, an effect not modeled by the
      algorithm. On the other hand, analysis of transient dispersion coefficients and
      comparison of lateral particle positions at the entry and exit hinted at non
      asymptotic behavior and a strong degree of correlation that was presumably a
      consequence of preferential high-velocity pathways in the raw sample block.
      Simulations with finite-sized probes resulted in particle trajectories that
      frequently terminated at narrow constrictions of the geometry. The amount of
      entrapment was predicted to increase monotonically with flow rate, evidently due
      to the relative contributions to transport by convection that carries particles
      to choke-points and diffusion that dislodges these entrapped particles. The
      overall effect is very similar to a flow-dependent entrapment phenomenon
      previously observed experimentally for adenovirus.

PMID- 22465687
TI  - Short- and long-term changes in extracellular glutamate and acetylcholine
      concentrations in the rat hippocampus following hypoxia.
AB  - Hypoxia at birth is a major source of brain damage and it is associated with
      serious neurological sequelae in survivors. Alterations in the extracellular
      turnover of glutamate (Glu) and acetylcholine (ACh), two neurotransmitters that
      are essential for normal hippocampal function and learning and memory processes,
      may contribute to some of the neurological effects of perinatal hypoxia. We set
      out to determine the immediate and long-lasting effects of hypoxia on the
      turnover of these neurotransmitters by using microdialysis to measure the
      extracellular concentration of Glu and ACh in hippocampus, when hypoxia was
      induced in rats at postnatal day (PD) 7, and again at PD30. In PD7 rats, hypoxia
      induced an increase in extracellular Glu concentrations that lasted for up to 2.5
      h and a decrease in extracellular ACh concentrations over this period. By
      contrast, perinatal hypoxia attenuated Glu release in asphyxiated rats, inducing
      a decrease in basal Glu levels when these animals reached PD30. Unlike Glu, the
      basal ACh levels in these animals were greater than in controls at PD30, although
      ACh release was stimulated less strongly than in control animals. These results
      provide the first evidence of the initial and long term consequences of the
      hypoxia on Glu and ACh turnover in the brain, demonstrating that hypoxia produces
      significant alterations in hippocampal neurochemistry and physiology.

PMID- 22465686
TI  - Fluazinam targets mitochondrial complex I to induce reactive oxygen species
      dependent cytotoxicity in SH-SY5Y cells.
AB  - Although the underlying cause of Parkinson's disease (PD) is not well
      characterized, epidemiological studies suggest that exposure to agricultural
      chemicals is a risk factor for PD. Fluazinam (FZN) is a new active ingredient for
      the control of grey mould, belonging to the novel broad spectrum
      phenylpyridinamine fungicides. We used human neuroblastoma SH-SY5Y cells to
      investigate mechanisms of dopaminergic cell death in response to FZN. FZN
      treatment produced dose-dependent cytotoxicity, and decreased the tyrosine
      hydroxylase (TH) expression in SH-SY5Y cells. We provided evidence for the
      occurrence of oxidative stress and oxidative damage during FZN exposure on
      dopaminergic cells through the measurement of reactive oxygen species (ROS) in
      cells with DCFH-DA. The cytotoxic effects of FZN appear to involve an increase in
      ROS generation since pretreatment with N-acetyl cysteine (NAC), an anti-oxidant,
      reduced cell death. After FZN treatment, dopamine (DA) levels decreased in both
      cell and culture media, and oxidative effects of FZN were blocked by NAC
      pretreatment. We show that cell death in response to FZN was due to apoptosis
      since FZN exposure results in an increased in cytochrome c release into the
      cytosol and activated caspase-3 through p38 and JNK signaling. Furthermore, the
      blocking of p38 or JNK signaling inhibits FZN-induced cell death. Phosphorylation
      of mitogen-activated protein kinases precedes cytochrome c release and caspase-3
      activation. This cellular response is characteristic of mitochondrial
      dysfunction. Therefore, we also investigated the effect of FZN on mitochondrial
      complex I activity in FZN-treated cell. Interestingly, we show that FZN inhibited
      the complex I activity. Thus in this study, we report a new mode of action by
      which the fungicide FZN could triggers apoptosis.

PMID- 22465688
TI  - Iloperidone (Fanapt(r)), a novel atypical antipsychotic, is a potent HERG blocker
      and delays cardiac ventricular repolarization at clinically relevant
      concentration.
AB  - QT interval prolongation on the electrocardiogram (ECG) has extensively been
      reported with iloperidone, a novel antipsychotic drug. The objective of the
      present study was to evaluate the effects of iloperidone on cardiac ventricular
      repolarization at three different levels; in vitro, ex vivo and in vivo. (1) In
      vitro level: whole-cell patch-clamp experiments were performed on HERG
      transfected HEK293 cells exposed to iloperidone 0.01-1 MUmol/L (n = 35 cells,
      total) to assess drug effect on HERG current. (2) Ex vivo level: Langendorff
      retroperfusion experiments were performed on isolated hearts from male Hartley
      guinea pigs (n = 7) exposed to iloperidone 100 nmol/L with/without chromanol 293B
      10 MUmol/L to assess drug-induced prolongation of monophasic action potential
      duration measured at 90% repolarization (MAPD(90)). (3) In vivo level: ECG
      recordings using wireless cardiac telemetry were performed in guinea pigs (n = 5)
      implanted with radio transmitters and treated with a single oral gavage dose of
      iloperidone 3 mg/kg. (1) Patch-clamp experiments revealed an estimated IC50 for
      iloperidone on HERG current of 161 +/- 20 nmol/L. (2) While pacing the hearts at
      stimulation cycle lengths of 200 or 250 ms, or during natural sinus rhythm (no
      external pacing), iloperidone 100 nmol/L prolonged MAPD(90) by respectively 9.2
      +/- 0.9, 11.2 +/- 1.6 and 21.4 +/- 2.3 ms. After adding chromanol 293B, MAPD(90)
      was further prolonged by 7.3 +/- 3.3, 11.5 +/- 2.3 and 29.2 +/- 6.7 ms,
      respectively. (3) Iloperidone 3mg/kg p.o. caused a maximal 42.7 +/- 10.2 ms
      prolongation of corrected QT interval (QTc(F)), 40 min after administration.
      Iloperidone prolongs the QT interval, the cardiac action potentials and is a
      potent HERG blocker. Patients are at increased risk of cardiac proarrhythmia
      during iloperidone treatment, as this drug possesses significant cardiac
      repolarization-delaying properties at clinically relevant concentration.

PMID- 22465689
TI  - The inaugural meeting of the North American Society for Comparative Endocrinology
      (NASCE; La Societe Nord-Americaine d'Endocrinologie Comparee; La Sociedad
      Norteamericana de Endocrinologia Comparada).

PMID- 22465690
TI  - Outcomes of children with complex regional pain syndrome after intensive
      inpatient rehabilitation.
AB  - OBJECTIVE: To examine the effectiveness of an inpatient treatment program on
      eliminating pain and increasing function for children with complex regional pain
      syndrome. DESIGN: A retrospective chart review and follow-up telephone survey.
      SETTING: A tertiary care hospital. PATIENTS: Retrospective chart review of 32
      children admitted for treatment of complex regional pain syndrome. Nineteen
      completed the telephone survey. INTERVENTION: Intensive inpatient physical and
      occupation therapy in conjunction with psychological counseling, art therapy,
      recreational therapy, and child life specialists who focused on improving
      physical function and conditioning, stress management, and the development of
      self-efficacy related to pain and stress. MAIN OUTCOME MEASUREMENTS: Resolution
      of pain and restoration of full function by patient or family report. RESULTS:
      All the children had failed various prior treatment approaches: 34% had
      resolution at the time of discharge; 78% of admissions and 89% of those with
      follow-up had eventual resolution of pain; and 95% had full restoration of
      physical function at a median time from start of treatment of 2 months. Seven had
      recurrence and 5 were able to resolve the recurrence without further intervention
      from the medical community. CONCLUSIONS: Intensive inpatient rehabilitation is
      effective for children with complex regional pain syndrome. Additional studies
      are necessary to compare this treatment with other approaches.

PMID- 22465691
TI  - Water channel proteins in the gastrointestinal tract.
AB  - Water transport through the human digestive system is physiologically crucial for
      maintaining body water homeostasis and ensure digestive and absorptive functions.
      Within the gastrointestinal tract, water recirculates, being secreted with the
      digestive juices and then almost entirely absorbed by the small and large
      intestine. The importance of aquaporins (AQPs), transmembrane water channel
      proteins, in the rapid passage of water across plasma membranes in the
      gastrointestinal tract appears immediately evident. Several AQP isoforms are
      found in gastrointestinal epithelia, with AQP1, 3, 7, 10 and 11 being the most
      abundantly expressed in the whole gut. On the other hand, AQP4 and 8 are located
      selectively in the stomach and colon, respectively. Here we review AQP expression
      and localization at the tissue, cellular and subcellular level in
      gastrointestinal epithelia, and their modification in various gut diseases.

PMID- 22465692
TI  - Excitation-contraction coupling in ventricular myocytes is enhanced by paracrine
      signaling from mesenchymal stem cells.
AB  - In clinical trials mesenchymal stem cells (MSCs) are transplanted into cardiac
      ischemic regions to decrease infarct size and improve contractility. However, the
      mechanism and time course of MSC-mediated cardioprotection are incompletely
      understood. We tested the hypothesis that paracrine signaling by MSCs promotes
      changes in cardiac excitation-contraction (EC) coupling that protects myocytes
      from cell death and enhances contractility. Isolated mouse ventricular myocytes
      (VMs) were treated with control tyrode, MSC conditioned-tyrode (ConT) or co
      cultured with MSCs. The Ca handling properties of VMs were monitored by laser
      scanning confocal microscopy and whole cell voltage clamp. ConT superfusion of
      VMs resulted in a time dependent increase of the Ca transient amplitude
      (ConT(15min): DeltaF/F(0)=3.52+/-0.38, n=14; Ctrl(15min):? DeltaF/F(0)=2.41+/
      0.35, n=14) and acceleration of the Ca transient decay (tau: ConT: 269+/-18ms
      n=14; vs. Ctrl: 315+/-57ms, n=14). Voltage clamp recordings confirmed a ConT
      induced increase in I(Ca,L) (ConT: -5.9+/-0.5 pA/pF n=11; vs. Ctrl: -4.04+/-0.3
      pA/pF, n=12). The change of tau resulted from increased SERCA activity. Changes
      in the Ca transient amplitude and tau were prevented by the PI3K inhibitors
      Wortmannin (100nmol/L) and LY294002 (10MUmol/L) and the Akt inhibitor V
      (20MUmol/L) indicating regulation through PI3K signal transduction and Akt
      activation which was confirmed by western blotting. A change in tau was also
      prevented in eNOS(-/-) myocytes or by inhibition of eNOS suggesting an NO
      mediated regulation of SERCA activity. Since paracrine signaling further resulted
      in increased survival of VMs we propose that the Akt induced change in Ca
      signaling is also a mechanism by which MSCs mediate an anti-apoptotic effect.

PMID- 22465694
TI  - Morphometric study of microvessels in primary CNS tumors and its correlation with
      tumor types and grade.
AB  - INTRODUCTION: Alterations of microvasculature are integral to CNS neoplasia, and
      a diagnostic feature of high-grade gliomas. The objectives of this study were two
      fold: First, to correlate morphometrically measured microvessel density (MVD),
      microvessel caliber (VC), and percentage of total microvessel area (%TVA) with
      WHO histologic grade in various types of primary CNS tumors. Second, to evaluate
      if such a correlation could be further refined by using mathematical derivatives
      of measured parameters namely coefficient of variation of VC (COofVC),
      microvessel cross-sectional area (VCSA), and percentage of total VCSA (%TVCSA).
      MATERIALS AND METHODS: Various microvessel parameters were assessed in a variety
      of 30 primary CNS tumors as consecutively encountered in routine surgical
      pathology practice including gliomas, meningiomas and others by image morphometry
      using CD34-immunostained sections. We introduced a novel method of effectively
      determining VC. Results were correlated with tumor type and grade. Appropriate
      statistical analysis was performed. RESULTS: Microvessel characteristics,
      especially VC (p<0.0022), VCSA (p<0.0164), CVofVC (p<0.0001), %TVCSA (p<0.0002)
      and %TVA (p<0.0003) of tumors were significantly greater than normal tissue. MVD
      increased in all tumors, excepting meningiomas, and was significantly higher in
      gliomas (p<0.0062). MVD showed negative correlation with VC (r=-0.808) and VCSA
      (r=-0.848) in the normal brain but was less significant in tumors. Unlike tumors,
      caliber distribution of microvessels in normal brain was noted to follow a
      Gaussian pattern. Histological grades of tumors showed positive correlation with
      MVD (r=0.547), VC (r=0.606), CVofVC (r=0.623), VCSA (r=0.485), %TVCSA (r=0.783)
      and %TVA (r=0.603). Calculated scores, estimated from multiple regressions of
      vessel parameters, correlated well with histological grade, with S2 (calculated
      using all measured as well as mathematically derived microvessel parameters)
      being better than S1 (calculated using measured parameters: MVD and VC).
      CONCLUSION: Tumor grades positively correlated with all microvessel parameters,
      with %TVCSA displaying the best. The correlation of %TVA with tumor grade was
      weaker than %TVCSA mainly due to the impact of MVD. These findings emphasize the
      value of VC as effectively measured using our novel method and best illustrated
      by its derivative %TVCSA (an indicator of blood flow), in addition to the well
      recognized value of MVD in tumor prognostication. Multiple regressions of
      microvessel parameters provided the best correlation with grade. Morphometric
      analysis of microvessels in CNS tumor facilitates a better understanding of the
      tumor grade, tumor progression and overall prognosis.

PMID- 22465693
TI  - Increased myofilament Ca2+ sensitivity and diastolic dysfunction as early
      consequences of Mybpc3 mutation in heterozygous knock-in mice.
AB  - Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in MYBPC3
      encoding cardiac myosin-binding protein C (cMyBP-C). The mechanisms leading from
      gene mutations to the HCM phenotype remain incompletely understood, partially
      because current mouse models of HCM do not faithfully reflect the human situation
      and early hypertrophy confounds the interpretation of functional alterations. The
      goal of this study was to evaluate whether myofilament Ca(2+) sensitization and
      diastolic dysfunction are associated or precede the development of left
      ventricular hypertrophy (LVH) in HCM. We evaluated the function of skinned and
      intact cardiac myocytes, as well as the intact heart in a recently developed
      Mybpc3-targeted knock-in mouse model carrying a point mutation frequently
      associated with HCM. Compared to wild-type, 10-week old homozygous knock-in mice
      exhibited i) higher myofilament Ca(2+) sensitivity in skinned ventricular
      trabeculae, ii) lower diastolic sarcomere length, and faster Ca(2+) transient
      decay in intact myocytes, and iii) LVH, reduced fractional shortening, lower E/A
      and E'/A', and higher E/E' ratios by echocardiography and Doppler analysis,
      suggesting systolic and diastolic dysfunction. In contrast, heterozygous knock-in
      mice, which mimic the human HCM situation, did not exhibit LVH or systolic
      dysfunction, but exhibited higher myofilament Ca(2+) sensitivity, faster Ca(2+)
      transient decay, and diastolic dysfunction. These data demonstrate that
      myofilament Ca(2+) sensitization and diastolic dysfunction are early phenotypic
      consequences of Mybpc3 mutations independent of LVH. The accelerated Ca(2+)
      transients point to compensatory mechanisms directed towards normalization of
      relaxation. We propose that HCM is a model for diastolic heart failure and this
      mouse model could be valuable in studying mechanisms and treatment modalities.

PMID- 22465695
TI  - Immunohistochemical screening for anaplastic lymphoma kinase (ALK) rearrangement
      in advanced non-small cell lung cancer patients.
AB  - Fluorescence in situ hybridization (FISH) is currently used to detect non-small
      cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) gene
      rearrangement, who are candidates for ALK inhibitor therapy. However, FISH may
      not be a practical method for screening for ALK-positive patients in a large
      population due to its cost and difficulty in interpretation. We investigated the
      role of immunohistochemistry (IHC) to screen for ALK rearrangement in advanced
      NSCLC. We identified 1,166 stage IIIB or IV NSCLC patients with non-squamous
      histology from the Seoul National University Hospital NSCLC database. To enrich
      ALK-positive cases, we selected 262 patients who were either EGFR wild-type or
      non-responders to previous EGFR tyrosine kinase inhibitors (TKI). ALK IHC and ALK
      FISH were performed on formalin-fixed, paraffin-embedded tissue. ALK protein was
      expressed in 28 (10.7%) tumors in 262 patients. ALK FISH was positive in 25
      (9.5%) cases. All patients with IHC score of 3 (n=9) were FISH-positive and all
      patients with score of 0 (n=234) were FISH-negative. Among patients with IHC
      scores of 1 and 2, five (83.3%, 5/6) and eleven (84.6%, 11/13) were FISH
      positive, respectively. The sensitivity and specificity of ALK IHC with intensity
      score of 1 or more were 100% and 98.7%, respectively. IHC can be a useful test
      for screening ALK FISH-positive cases in advanced NSCLC. FISH testing should be
      considered for advanced NSCLC patients with tumors showing mild to moderate
      staining for ALK by IHC to confirm ALK translocation.

PMID- 22465696
TI  - d-Serine diffusion through the blood-brain barrier: effect on d-serine
      compartmentalization and storage.
AB  - d-Serine is a co-agonist of N-methyl-d-aspartate (NMDA) receptors. It has been
      implicated in the etiology of schizophrenia and has shown efficacy as an adjuvant
      to reduce positive and negative symptoms of schizophrenia. In addition, d-serine
      can modulate cognition in animals when administered alone. However, the
      neurochemical effects of exogenous d-serine on extra- and intra-cellular d-serine
      brain levels are poorly understood. In this study, we used both high performance
      liquid chromatography (HPLC) and enzyme-based microelectrode biosensors to
      quantify d-serine in the rat brain. We demonstrated levels of 2.3-2.8MUM in the
      extracellular medium, 4MUM in plasma and 188pmol/mg in brain tissue samples. An
      intraperitoneal (i.p.) d-serine injection (1g/kg) produced a slow increase in
      extracellular d-serine concentration in the cortex despite a surge in d-serine up
      to 13mM in the plasma, indicating poor diffusion through the blood-brain barrier.
      Using the respective volume fractions of blood, extracellular and intracellular
      spaces published in the literature, we estimated that d-serine intracellular
      stores represented more than 99% of total d-serine. These intracellular stores
      almost doubled 3h after d-serine administration. Overall, our data indicate that
      d-serine administration increases brain extra- and intra-cellular concentrations
      despite weak diffusion through the blood-brain barrier. These results pave the
      way for a better understanding of the neurochemical mechanisms by which d-serine
      administration modulates cognition.

PMID- 22465697
TI  - The association between plasma homocysteine levels, methylation capacity and
      incident osteoporotic fractures.
AB  - BACKGROUND: An elevated level of plasma homocysteine (Hcy) is a known risk factor
      for osteoporotic fractures. In addition, Hcy is related to DNA-methylation
      metabolism. To determine whether the association between Hcy and fractures is
      explained by an altered methylation capacity, we investigated the associations
      between levels of s-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) and
      fracture risk. METHODS: We studied 503 females aged 55 years and over from the
      Rotterdam Study (RS) in whom plasma Hcy, SAM and SAH levels were measured. Bone
      mineral density (BMD) at the hip was assessed using DXA. Incident fractures were
      recorded over a mean period of 7.0 years. Cox proportional hazards analysis and
      linear regression were used to assess relationships between plasma metabolite
      levels, incident osteoporotic fractures and BMD. RESULTS: Over a total of 3502
      person-years of follow-up, 103 subjects sustained at least one osteoporotic
      fracture. Whereas incidence of osteoporotic fractures was associated with
      quartiles of Hcy (p=0.047), it was not associated with quartiles of SAM, SAH or
      SAM/SAH-ratio (all p for trend>0.6). Stepwise linear regression showed that
      SAM/SAH-ratio, but not Hcy, was independently associated with hip BMD
      (beta=0.073, p=0.025). CONCLUSION: Since SAM, SAH and SAM/SAH-ratio were not
      associated with osteoporotic fractures, alterations in methylation capacity most
      likely do not appear to be an important factor in the association between Hcy and
      fractures.

PMID- 22465698
TI  - The significance of preoperative leukocytosis in endometrial carcinoma.
AB  - OBJECTIVE: To evaluate the impact of preoperative leukocytosis among patients
      with endometrial carcinoma. METHODS: The medical records of all patients that
      underwent surgical treatment for endometrial carcinoma between January 2005 and
      December 2010 were retrospectively reviewed. Patients were separated into two
      groups based on the presence or absence of preoperative leukocytosis (WBC >=
      10,000 cells per MUl). The groups were then compared with respect to pathologic
      findings, progression-free survival and overall survival. RESULTS: 1144 patients
      were identified, 156 (13.6%) with preoperative leukocytosis and 988 (86.4%)
      without leukocytosis. The leukocytosis group had a greater percentage of patients
      with stage 3 (15.4% vs. 9.8%, crude p=0.02) and 4 (7.1% vs. 3.0%, crude p=0.007)
      disease. Leukocytosis was associated with a greater mean tumor size (4.4 vs. 3.4
      cm, p=0.0002) and a greater percentage of patients with cervical stromal
      involvement (14.8% vs. 8.7%, crude p=0.02), adnexal involvement (14.1% vs. 7.5%,
      crude p=0.007) and lymphvascular space invasion (24% vs. 16.3%, crude p=0.02). On
      multivariate analysis, mean tumor size (OR, 95% CI; 1.10, 1.02-1.18) remained
      significantly associated with preoperative leukocytosis. There was no difference
      between groups, with respect to time to recurrence. However, leukocytosis was
      independently associated with an increased risk of death (HR, 95% CI; 1.69, 1.07
      2.68). CONCLUSIONS: Preoperative leukocytosis, among endometrial cancer patients,
      was independently associated with increasing tumor size and independently imposed
      an increased risk of death.

PMID- 22465699
TI  - Looking after children and young people: ensuring their voices are heard in the
      pre-registration nursing curriculum.
AB  - 'Looked after Children' refers to those under the age of 18 years, who have been
      subject to a care order under The Children Act (1989). In England there are
      approximately 64,400 young people who are subject of a care order, with evidence
      suggesting that these young people are likely to experience greater health
      problems than their peers. While service user involvement is seen as integral to
      the nursing curriculum much of the literature to date has revolved around adult
      service users and carers. For a number of years professionals have been urged to
      hear the voices of young service users and carers, and in particular, those who
      regularly use health and social care services. This paper will highlight the
      importance of collaborating with looked after children and young people to inform
      the nursing curriculum. By focussing on the experiences of delivering a seminar
      in collaboration with this group of young people in a pre-registration BSc (Hons)
      in Children's Nursing, the paper will first describe how the session is organised
      followed by a discussion of the key issues arising these being explored from a
      nurse lecturer and student nurse perspective.

PMID- 22465701
TI  - Logic and evaluation theory.
AB  - With this series of papers, evaluators are being called to substantiate the
      rationale and warrant for their own evaluative actions in ways parallel to how
      evaluators question the logic of program interventions, both as designed and as
      implemented. This endeavor is timely, appropriate, and important. In these
      comments, I raise modest questions about the logical constitution of an
      evaluation theory and about what is missing from a textual reading alone of such
      theory.

PMID- 22465700
TI  - Platinum(IV)-chlorotoxin (CTX) conjugates for targeting cancer cells.
AB  - Cisplatin is one of the most widely used anticancer drugs. Its side effects,
      however, have motivated researchers to search for equally effective analogs that
      are better tolerated. Selectively targeting cancer tissue is one promising
      strategy. For this purpose, a platinum(IV) complex was conjugated to the cancer
      targeting peptide chlorotoxin (CTX, TM601) in order to deliver cisplatin
      selectively to cancer cells. The 1:1 Pt-CTX conjugate was characterized by mass
      spectrometry and gel electrophoresis. Like most platinum(IV) derivatives, the
      cytotoxicity of the conjugate was lower in cell culture than that of cisplatin,
      but greater than those of its Pt(IV) precursor and CTX in several cancer cell
      lines.

PMID- 22465702
TI  - Depicting the logic of three evaluation theories.
AB  - Here, we describe the development of logic models depicting three theories of
      evaluation practice: Practical Participatory (Cousins & Whitmore, 1998), Values
      engaged (Greene, 2005a, 2005b), and Emergent Realist (Mark et al., 1998). We
      begin with a discussion of evaluation theory and the particular theories that
      were chosen for our analysis. We then outline the steps involved in constructing
      the models. The theoretical prescriptions and claims represented here follow a
      logic model template developed at the University Wisconsin-Extension (Taylor
      Powell & Henert, 2008), which also closely aligns with Mark's (2008) framework
      for research on evaluation.

PMID- 22465703
TI  - Coordination of trunk and pelvis in young and elderly individuals during axial
      trunk rotation.
AB  - It has been well known that complex tasks such as walking and arm reaching can be
      achieved by the coordination of the trunk and pelvis. However, understanding of
      the effect of aging on the coordination of the trunk and pelvis during axial
      trunk rotation is still lacking. The present study examined relative phase of the
      trunk and pelvis during axial trunk rotation, and compared it between young and
      older groups. 22 healthy young (age: 23.9+/-4.6, gender: 11 male and 11 female)
      and 22 healthy elderly (age: 68.4+/-4.9, gender: 11 male and 11 female)
      individuals participated in the experiment and performed axial trunk rotation.
      Relative phase between the trunk and pelvis was calculated based on the angular
      displacements of the two segments. The results demonstrated age-related changes
      in coordination pattern of the trunk and pelvis during axial trunk rotation.

PMID- 22465704
TI  - Do somatosensory conditions from the foot and ankle affect postural responses to
      plantar-flexor muscles fatigue during bipedal quiet stance?
AB  - The present study investigated the effects of somatosensory conditions at the
      foot and ankle on postural responses to plantar-flexor muscle fatigue during
      bipedal quiet stance. Twenty-two young healthy adults were asked to stand upright
      as still as possible with their eyes closed in three somatosensory conditions
      (normal, altered and improved) both prior to and after exercises inducing plantar
      flexor muscle fatigue. In the normal condition, the postural task was executed on
      a firm support surface constituted by the force platform. In the altered
      condition, a 2-cm thick foam support surface was placed under the subjects' feet.
      In the improved condition, increased cutaneous feedback at the foot and ankle was
      provided by strips of athletic tape applied across both their ankle joints.
      Muscle fatigue was induced in the plantar-flexor muscles of both legs through the
      execution of a repeated standing heel raise exercise. Centre of foot pressure
      displacements were recorded using a force platform. Results showed that plantar
      flexor muscle fatigue yielded increased centre of foot pressure displacements
      under normal foot and ankle sensory conditions. Furthermore, this effect was
      exacerbated under altered foot and ankle sensory conditions and mitigated under
      improved foot and ankle sensory conditions. Altogether, the present findings
      suggested an increased reliance on somatosensory information from the foot and
      ankle for controlling upright posture in the presence of plantar-flexor muscle
      fatigue.

PMID- 22465705
TI  - An enhanced estimate of initial contact and final contact instants of time using
      lower trunk inertial sensor data.
AB  - This study introduces a new method of extracting initial and final contact gait
      time events from vertical acceleration, measured with one waist mounted inertial
      measurement unit, by means of continuous wavelet transforms. The method was
      validated on 18 young healthy subjects and compared to two others available in
      the literature. Of the three methods investigated, the new one was the most
      accurate at identifying the existence and timing of initial and final contacts
      with the ground, with an average error of 0.02+/-0.02 s and 0.03+/-0.03 s
      (approximately 2% and 3% of mean stride duration), respectively.

PMID- 22465706
TI  - Interference between walking and a cognitive task is increased in patients with
      bilateral vestibular loss.
AB  - The aim of this study was to determine whether there is more deterioration in
      walking under dual-task conditions in patients with bilateral vestibular loss
      (BVL) than in healthy subjects, as opposed to the findings after unilateral loss.
      For this purpose, 12 patients with BLV and 12 healthy control subjects performed
      3 tasks: walking along a 10-m walkway, counting backwards by two, and both tasks
      simultaneously. Patients did not differ from controls in their walking speed in
      the single task condition, or in their cognitive performance in both the single
      and dual-task conditions. However, walking performance was more affected in
      patients than in controls under dual-task conditions, as shown by slower gait
      speed in the dual-task, higher reduction in gait speed from single to dual-task,
      and lower global dual-score. These findings provide evidence for greater
      attentional interference between walking and counting in patients with BVL.

PMID- 22465707
TI  - Regulation of whole-body frontal plane balance varies within a step during
      unperturbed walking.
AB  - This study sought to determine whether the need to actively control lateral
      balance is consistent within a step. Variability of the frontal plane COM-Ankle
      angle was calculated over 50 strides at discrete gait events for twenty-one
      healthy young adults to quantify active control of lateral balance within a step.
      Frontal plane COM-Ankle angle variability was found to vary significantly between
      all gait events, decreasing progressively within a step. This suggests that
      active control of lateral balance varies significantly within a step and that the
      greatest degree of active control occurs at heel-strike. The increased active
      control of lateral balance during heel-strike indicates a degree of preparation
      to ensure sufficient lateral balance control prior to more challenging events.
      These results provide insight into the mechanisms of lateral balance control and
      how to assess and treat locomotor balance control impairments.

PMID- 22465708
TI  - Microtubule-associated protein light chain 3 regulates Cdc42-dependent actin ring
      formation in osteoclast.
AB  - Microtubule-associated protein 1 light chain-3 (LC3) plays a critical role in
      autophagosome formation during autophagy; however, its potential alternative
      functions remain largely unexplored. Here we demonstrate a discrete role for LC3
      in osteoclast, a specialized bone-resorbing cell that requires a dynamic
      microtubule network for its activity. We found that an increase in the conversion
      of soluble LC3-I to lipid-bound LC3-II in mature osteoclast was correlated with
      osteoclast activity, but not with autophagic activity. Knockdown of LC3 using
      small interfering RNA did not affect TRAP-positive multinucleated cell formation,
      but suppressed actin ring formation, cathepsin K release, and the subsequent bone
      resorbing capacity of osteoclasts. LC3 mediated this function by associating with
      microtubules and regulating Cdc42 activity. More importantly, LC3-II protein
      levels were reduced by the Atg5 knockdown, and this knockdown led to decrease in
      Cdc42 activity, indicating that LC3-II is critical for Cdc42 activity.
      Overexpression of a constitutively active form of Cdc42 partially rescued the
      phenotype induced by LC3 knockdown. Our results demonstrate that LC3 contributes
      to the regulatory link between the microtubule and Cdc42 involved in bone
      resorbing activity, providing evidence for a role for LC3 in mediating diverse
      cellular functions beyond its role as an autophagy protein.

PMID- 22465709
TI  - DNA topoisomerase IIbeta: a player in regulation of gene expression and cell
      differentiation.
AB  - DNA topoisomerases II regulate conformational changes in DNA topology. They act
      on double-stranded DNA, catalyzing its relaxation, decatenation and unknotting.
      Vertebrate cells express two isoforms of topoisomerase II, which are similar in
      structure, but different in function and regulation. Whereas the alpha isoform is
      indispensable for proper cell replication, the functions of the beta isoform as
      well as reasons for its evolution in vertebrates were long unclear. Unlike
      topoisomerase II alpha, the beta isoform is predominantly expressed in quiescent
      cells and has been implicated mainly in the process of gene transcription.
      Recently, new discoveries point on the role of the topoisomerase II beta in
      regulation of cellular differentiation and tissue development. Furthermore,
      contemporary discoveries are raising possibilities for novel therapeutic
      approaches involving selective targeting of either topoisomerase II isoform in
      potentiating antitumor and/or reducing adverse effects of topoisomerase II
      poisons.

PMID- 22465710
TI  - Up-regulating ribonuclease inhibitor inhibited epithelial-to-mesenchymal
      transition and metastasis in murine melanoma cells.
AB  - Human ribonuclease inhibitor (RI) is a cytoplasmic acidic protein. RI is
      constructed almost entirely of leucine rich repeats, which might be involved in
      unknown biological effects except inhibiting RNase A and angiogenin activities.
      We previously reported that up-regulating RI inhibited the growth and metastasis
      of melanoma cells. Epithelial-mesenchymal transition (EMT) is a critical event of
      cancer cells that triggers invasion and metastasis. However, the role of RI in
      the EMT process remains unknown. Here we hypothesize that RI might inhibit
      melanoma invasion and metastasis by regulating EMT. We found that over-expression
      of RI induced up-regulation of E-cadherin, accompanied with decreased expressions
      of proteins associated with EMT such as N-cadherin, Snail, Slug, Vimentin and
      Twist both in vitro and in vivo. Furthermore, RI restrained matrix
      metalloproteinase MMP-2 and MMP-9 secretions in B16 and B16-F10 melanoma cells.
      In addition, we also found that up-regulation of RI inhibited cell proliferation,
      migration and invasion as well as changed cell morphology, adhesion and
      rearranged cytoskeleton in vitro. Finally, the effects of RI on phenotype and
      invasiveness translated into suppressing metastasis by the experimental
      metastasis models of melanoma with lighter lung weight, a fewer metastasis
      nodules and a lower incidence rate, with respect to the control groups. Taken
      together, our data highlight, for the first time, that RI plays a novel role in
      inhibiting development and progression of murine melanoma cells through
      regulating EMT. These results suggest that RI could be a therapeutic target
      protein for melanoma and may be of biological importance.

PMID- 22465711
TI  - Insulin receptor substrate protein 53kDa (IRSp53) is a negative regulator of
      myogenic differentiation.
AB  - Fusion of mononucleated myoblasts to generate multinucleated myotubes is a
      critical step in skeletal muscle development. Filopodia, the actin cytoskeleton
      based membrane protrusions, have been observed early during myoblast fusion,
      indicating that they could play a direct role in myogenic differentiation. The
      control of filopodia formation in myoblasts remains poorly understood. Here we
      show that the expression of IRSp53 (Insulin Receptor Substrate protein 53kDa), a
      known regulator of filopodia formation, is down-regulated during differentiation
      of both mouse primary myoblasts and a mouse myoblast cell line C2C12. Over
      expression of IRSp53 in C2C12 cells led to induction of filopodia and decrease in
      cell adhesion, concomitantly with inhibition of myogenic differentiation. In
      contrast, knocking down the IRSp53 expression in C2C12 cells led to a small but
      significant increase in myotube development. The decreased cell adhesion of C2C12
      cells over-expressing IRSp53 is correlated with a reduction in the number of
      vinculin patches in these cells. Mutations in the conserved IMD domain (IRSp53
      and MIM (missing in metastasis) homology domain) or SH3 domain of IRSp53
      abolished the ability of this protein to inhibit myogenic differentiation and
      reduce cell adhesion. Over-expression of the IMD domain alone was sufficient to
      decrease the cell-extracellular matrix adhesion and to inhibit myogenesis in a
      manner dependent on its function in membrane shaping. Based on our data, we
      propose that IRSp53 is a negative regulator of myogenic differentiation which
      correlates with the observed down regulation of IRSp53 expression during myoblast
      differentiation to myotubes.

PMID- 22465712
TI  - An optimized predictor panel for colorectal cancer diagnosis based on the
      combination of tumor-associated antigens obtained from protein and phage
      microarrays.
AB  - Humoral response in cancer patients appears early in cancer progression and can
      be used for diagnosis, including early detection. By using human recombinant
      protein and T7 phage microarrays displaying colorectal cancer (CRC)-specific
      peptides, we previously selected 6 phages and 6 human recombinant proteins as
      tumor-associated antigens (TAAs) with high diagnostic value. After completing
      validation in biological samples, TAAs were classified according to their
      correlation, redundancy in reactivity patterns and multiplex diagnostic
      capabilities. For predictor model optimization, TAAs were reanalyzed with a new
      set of samples. A combination of three phages displaying peptides homologous to
      GRN, NHSL1 and SREBF2 and four proteins PIM1, MAPKAPK3, FGFR4 and ACVR2B,
      achieved an area under the curve (AUC) of 94%, with a sensitivity of 89.1% and
      specificity of 90.0%, to correctly predict the presence of cancer. For early
      colorectal cancer stages, the AUC was 90%, with a sensitivity of 88.2% and
      specificity of 82.6%. In summary, we have defined an optimized predictor panel,
      combining TAAs from different sources, with highly improved accuracy and
      diagnostic value for colorectal cancer. This article is part of a Special Issue
      entitled: Translational Proteomics.

PMID- 22465713
TI  - Downregulation of Na(+)-NQR complex is essential for Vibrio alginolyticus in
      resistance to balofloxacin.
AB  - Increasingly isolated frequency of antibiotic-resistant V. alginolyticus strains
      in clinic and aquaculture has been reported, but the mechanisms of V.
      alginolyticus antibiotic resistance are largely absent. In the present study,
      native/SDS-PAGE based proteomics, which may provide information on protein
      protein interaction, was utilized to investigate differential proteins of V.
      alginolyticus in resistance to balofloxacin. Ten proteins were altered, in which
      V12G01_04671, V12G01_00457, V12G01_15927, V12G01_15240, NqrA (spot 26), and NqrF
      (spot 30) were downregulated, while V12G01_22043, TolC, V12G01_15130,
      V12G01_19297 were upregulated. Importantly, the two components of Na(+)-NQR
      complex, NqrA and NqrF, were vertically lined and was further investigated.
      Western blotting assay indicated that downregulation of the two proteins
      contrasted sharply with upregulation of a control protein TolC, which was
      consistent with the result obtained from 2-DE gel analysis. Furthermore,
      overexpression of NqrA, NqrF and TolC resulted in decrease and elevation of
      bacterial survival ability in medium with balofloxacin, respectively. These
      results indicate that downregulation of Na(+)-NQR complex is essential for V.
      alginolyticus resistance to balofloxacin. This is the first report on the role of
      Na(+)-NQR complex in antibiotic resistance. This finding highlights the way to an
      understanding of antibiotic-resistant mechanisms in content of metabolic
      regulation.

PMID- 22465714
TI  - Targeted functional analysis of p300 coactivator in Wnt/beta-catenin signaling
      pathway using phosphoproteomic and biochemical approaches.
AB  - Both p300 and beta-catenin are transcriptional activators and phosphoproteins,
      and play a central role in Wnt/beta-catenin-dependent transcriptional regulation.
      The minimum beta-catenin binding domain of p300 has been mapped to the N-terminus
      1-111 amino acids. Here, we performed phosphoproteomic analysis for the critical
      binding region using LC-MS/MS approach to investigate potential phosphosites that
      may affect the binding affinity. By implementing TiO(2)-based phosphopeptide
      affinity purification followed by LC-MS/MS analysis with both collision-induced
      dissociation (CID) and electron transfer dissociation (ETD) methods, two unique
      phosphosites Ser12 and Ser89 were identified, of which, phosphorylation at Ser12
      is novel. Functional studies aided by site-directed mutagenesis, co
      immunoprecipitation and mammalian two-hybrid assay have concluded that
      phosphorylation at Ser12 critically mediates the binding ability of p300 with
      beta-catenin. Further studies utilizing specific MAPK inhibitors suggest that the
      p38 MAPK activation is the upstream signal required for Ser12 phosphorylation.
      The transcriptional roles of p300/beta-catenin complex in myoblast
      differentiation are discussed.

PMID- 22465715
TI  - Alterations of red blood cell metabolome during cold liquid storage of
      erythrocyte concentrates in CPD-SAGM.
AB  - Erythrocyte concentrates for transfusion purposes represent a life-saving
      therapeutics of primary relevance in the clinical setting. However, efforts have
      been continuously proposed to improve safety and efficacy of long-term stored red
      blood cells. By means of liquid chromatography coupled with Q-TOF mass
      spectrometry, we were able to perform an untargeted metabolomics analysis in
      order to highlight metabolic species (i.e. low molecular biochemicals including
      sugars, lipids, nucleotides, aminoacids, etc.), both in red blood cells and
      supernatants, which showed fluctuations against day 0 controls over storage
      duration on a weekly basis. We could confirm and expand existing literature about
      the rapid fall of glycolytic rate and accumulation of glycolysis end products. A
      shift was observed towards the oxidative phase of pentose phosphate pathway, in
      response to an exacerbation of oxidative stress (altered glutathione homeostasis
      and accumulation of peroxidation/inflammatory products in the supernatant). The
      present study provides the first evidence that over storage duration metabolic
      fluxes in red blood cells proceed from pentose phosphate pathway towards purine
      salvage pathway, instead of massively re-entering glycolysis via the nonoxidative
      phase. This article is part of a Special Issue entitled: Integrated omics.

PMID- 22465717
TI  - Novel pancreatic beta cell-specific proteins: antibody-based proteomics for
      identification of new biomarker candidates.
AB  - Beta cell-specific surface targets are required for non-invasive monitoring of
      beta cell mass, which could be used for evaluation of new diabetes treatments as
      well as to help unravel pathogenic mechanisms underlying beta cell dysfunction.
      By antibody-based proteomics, we have identified and explored a set of islet cell
      specific proteins. A search algorithm in the Human Protein Atlas was set up for
      identification of islet-specific proteins that yielded 27 hits, of which twelve
      showed a clear membranous expression pattern or had predicted transmembrane
      regions. The specificity of the identified proteins was investigated by
      immunohistochemical staining of pancreas sections from diabetic and non-diabetic
      subjects. No expression of these antigens could be detected in the exocrine
      pancreas. Colocalization with insulin and glucagon was further determined by
      confocal microscopy using isolated human islets. All antibodies specifically
      stained human islets and colocalization analysis revealed that four proteins were
      exclusively expressed in beta cells. Importantly, these antibodies were negative
      in sections from subjects with long-standing type 1 diabetes. In the present
      study, we present four proteins; DGCR2, GBF1, GPR44 and SerpinB10, the expression
      of which has not previously been described in beta cells.

PMID- 22465716
TI  - Probing neuropeptide signaling at the organ and cellular domains via imaging mass
      spectrometry.
AB  - Imaging mass spectrometry (IMS) has evolved to be a promising technology due to
      its ability to detect a broad mass range of molecular species and create density
      maps for selected compounds. It is currently one of the most useful techniques to
      determine the spatial distribution of neuropeptides in cells and tissues.
      Although IMS is conceptually simple, sample preparation steps, mass analyzers,
      and software suites are just a few of the factors that contribute to the
      successful design of a neuropeptide IMS experiment. This review provides a brief
      overview of IMS sampling protocols, instrumentation, data analysis tools,
      technological advancements and applications to neuropeptide localization in
      neurons and endocrine tissues. Future perspectives in this field are also
      provided, concluding that neuropeptide IMS would greatly facilitate studies of
      neuronal network and biomarker discovery.

PMID- 22465718
TI  - [Smoking and tuberculosis].
AB  - Smoking and tuberculosis represent two major world health issues particularly in
      developing countries. Tobacco smoke increases risk of Mycobaterium tuberculosis
      infection by several means: alteration of muco-ciliary clearance, reduced
      alveolar macrophage activity; immune-depression of pulmonary lymphocytes,
      reduction of cytotoxic activity of natural killer cells, alteration of the
      activity of the pulmonary dendritic cells. Both active and passive smoking
      increases the risk of latent tubercular infection and of pulmonary and extra
      pulmonary tuberculosis. Active smoking increases the severity of pulmonary
      tuberculosis (gravity of radiological lesions). The diagnostic delay and recovery
      details are more important for smokers. Active smoking increases relapses of both
      pulmonary and extra-pulmonary tuberculosis after treatment with or without the
      Directly Observed Treatment Short course (DOTS) with poor observance of
      treatment. The mortality risk from tuberculosis is heightened among smokers.
      Smoking cessation represents an essential means of controlling tuberculosis
      epidemics in developing countries.

PMID- 22465719
TI  - [Going from research to development: which support and financing tools?].

PMID- 22465720
TI  - [Should we consume less salt?].
AB  - There is overwhelming evidence that dietary salt is a major cause of increased
      blood pressure. There is also a link between a high salt intake and risk of
      stroke, left ventricular hypertrophy, renal disease, obesity, renal stones and
      stomach cancer. Reduction of salt intake is efficacious and cost-effective. In
      developed countries, reduction in salt intake requires the participation of food
      industry.

PMID- 22465721
TI  - "De-liver-ance" from CB(1): a way to counteract insulin resistance?

PMID- 22465722
TI  - An unusual cause of biliary obstruction after endoscopic sphincterotomy.

PMID- 22465724
TI  - Endoscopic subtlety: rest assured only when biopsied.

PMID- 22465726
TI  - Moisture effects on greenhouse gases generation in nitrifying gas-phase compost
      biofilters.
AB  - Gas-phase compost biofilters are extensively used in concentrated animal feeding
      operations to remove odors and, in some cases, ammonia from air sources. The
      expected biochemical pathway for these predominantly aerobic systems is
      nitrification. However, non-uniform media with low oxygen levels can shift
      biofilter microbial pathways to denitrification, a source of greenhouse gases.
      Several factors contribute to the formation of anoxic/anaerobic zones: media
      aging, media and particle structure, air velocity distribution, compaction,
      biofilm thickness, and moisture content (MC) distribution. The present work
      studies the effects of media moisture conditions on ammonia (NH(3)) removal and
      greenhouse gas generation (nitrous oxide, N(2)O and methane, CH(4)) for gas-phase
      compost biofilters subject to a 100-day controlled drying process. Continuous
      recordings were made for the three gases and water vapor (2.21-h sampling cycle,
      each cycle consisted of three gas species, and water vapor, for a total of 10,050
      data points). Media moisture conditions were classified into three corresponding
      media drying rate (DR) stages: Constant DR (wetter media), falling DR, and stable
      dry system. The first-half of the constant DR period (0-750 h; MC=65-52%, w.b.)
      facilitated high NH(3) removal rates, but higher N(2)O generation and no CH(4)
      generation. At the drier stages of the constant DR (750-950 h; MC=52-48%, w.b.)
      NH(3) removal remained high but N(2)O net generation decreased to near zero. In
      the falling DR stage (1200-1480 h; MC=44-13%) N(2)O generation decreased, CH(4)
      increased, and NH(3) was no longer removed. No ammonia removal or greenhouse gas
      generation was observed in the stable-dry system (1500-2500 h; MC=13%). These
      results indicate that media should remain toward the drier region of the constant
      DR (in close proximity to the falling DR stage; MC=50%, approx.), to maintain
      high levels of NH(3) removal, reduced levels of N(2)O generation, and nullify
      levels of CH(4) generation.

PMID- 22465725
TI  - The association of macro- and micronutrient intake with growth hormone secretion.
AB  - CONTEXT: Growth hormone (GH) is known to be nutritionally regulated, but the
      effect of dietary composition on detailed GH secretion parameters has not
      previously been comprehensively evaluated. OBJECTIVE: The objective of the study
      was to determine whether specific macro- and micronutrients are associated with
      discrete parameters of GH secretion among subjects with wide ranges of body mass
      index. DESIGN: Detailed macro- and micronutrient intake was assessed by 4-day
      food records while GH secretion was assessed by standard stimulation testing in
      108 men and women in one study (Study 1), and by overnight frequent blood
      sampling in 12 men in another study (Study 2). RESULTS: Peak stimulated GH was
      positively associated with vitamin C (r=+0.29; P=0.003), dietary fiber (r=+0.27;
      P=0.004), arachidic acid (r=+0.25; P=0.008), and behenic acid (r=+0.30; P=0.002)
      intake in univariate analysis. Controlling for age, gender, race/ethnicity,
      visceral fat, HOMA-IR, total caloric intake and these four dietary factors in
      step-wise multivariate modeling, peak GH remained significantly associated with
      vitamin C and visceral fat (both P<0.05). In addition, vitamin C intake was
      associated with various parameters of endogenous GH secretion including basal GH
      secretion (r=+0.95; P<0.0001), GH half-life (r=+.75; P=0.005), total GH
      production (r=+0.76; P=0.004), GH area-under-the-curve (r=+0.89; P=0.0001), mean
      log(10) GH pulse area (r=+0.67; P=0.02), and overnight maximum (r=+0.62; P=0.03),
      nadir (r=+0.97; P<0.0001), and mean GH secretion (r=+0.89; P=0.0001).
      CONCLUSIONS: These results suggest that certain micronutrients such as vitamin C
      intake are strongly and uniquely associated with stimulated and endogenous
      spontaneous GH secretion.

PMID- 22465727
TI  - One-year weekly survey of noroviruses and enteric adenoviruses in the Tone River
      water in Tokyo metropolitan area, Japan.
AB  - To investigate the actual fluctuations in the concentrations of noroviruses
      (NoVs) GI and GII, and enteric adenoviruses (EAdVs) in river water and its
      relationship with the number of acute infectious gastroenteritis patients, one
      year weekly quantitative monitoring of NoVs GI and GII and EAdVs was performed in
      the Tone River in Japan where the surface water is utilized for the main
      production of drinking water for the Tokyo Metropolitan Area from October 2009 to
      September 2010. Noroviruses GI and GII and EAdVs were detected in 28 (54%), 33
      (63%), and 23 (44%) of the 52 samples (1 L each), respectively. The
      concentrations of NoVs GI and GII and EAdVs fluctuated strongly and were more
      abundant in winter and early spring. The concentration of NoVs GI was transiently
      greater than 10,000 copies/L. The number of acute infectious gastroenteritis
      patients in the upper river basin was highly correlated with all the viral
      concentrations, while general microbial indicator data such as turbidity and
      heterotrophic plate count were independent of viral concentration as suggested in
      previous studies. To the best of our knowledge, this is the first study that
      clearly shows the strong correlation of the number of gastroenteritis with virus
      contamination in lower river basin.

PMID- 22465728
TI  - Mechanisms underlying the diuretic effects of Tropaeolum majus L. extracts and
      its main component isoquercitrin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have shown that the extracts
      obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ),
      exhibit pronounced diuretic effects, supporting the ethnopharmacological use of
      this plant. The aim of this study was to evaluate the efficacy and mechanisms
      underlying the diuretic action of an ethanolic extract of Tropaeolum majus
      (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously
      hypertensive rats (SHR). MATERIALS AND METHODS: The diuretic effects of HETM
      (300mg/kg; p.o.), TMLR (100mg/kg; p.o.), and ISQ (10mg/kg; p.o.), were compared
      with classical diuretics in 7days repeated-dose treatment. The urinary volume,
      sodium, potassium, chloride, bicarbonate, conductivity, pH and density were
      estimated in the sample collected for 15h. The plasmatic concentration of sodium,
      potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin
      converting enzyme (ACE) activity were measured in samples collected at the end of
      the experiment (seventh day). Using pharmacological antagonists or inhibitors, we
      determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in
      ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity
      of erythrocytary carbonic anhydrase and renal Na(+)/K(+)/ATPase were evaluated in
      vitro. RESULTS: HETM, TMLR and ISQ increased diuresis similarly to spironolactone
      and also presented K(+)-sparing effects. All groups presented both plasmatic
      aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a
      B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor),
      or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In
      addition, the 7days treatment with ISQ resulted in increased plasmatic levels of
      nitrite and reducing ROS production. Moreover, the renal Na(+)/K(+)/ATPase
      activity was significantly decreased by ISQ. CONCLUSION: Our results suggest that
      the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in
      SHR rats are mainly related to ACE inhibition, increased bioavailability of
      bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na(+)/K(+)
      ATPase.

PMID- 22465729
TI  - Bryonia dioica aqueous extract induces apoptosis through mitochondrial intrinsic
      pathway in BL41 Burkitt's lymphoma cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bryonia dioica Jacq. is a climbing perennial herb
      with tuberous roots which is widely used in traditional medicine in Algeria for
      the treatment of cancers; it belongs to the genus Bryonia (Cucurbitaceae). AIM OF
      THE STUDY: To investigate the cytotoxic and apoptogenic activities, the
      phytochemical composition and acute toxicity of the aqueous extract of Bryonia
      dioica roots growing in Algeria. MATERIALS AND METHODS: Dried roots of Bryonia
      dioica were extracted with water (decoction). The cytotoxic effects of the
      aqueous extract in the Burkitt's lymphoma BL41 cell lines were evaluated by flow
      cytometry. Apoptosis induction was assessed by two corroborative assays;
      propidium iodide (PI) staining of cell DNA and flow cytometric light scatter
      analysis. The mitochondria membrane potential was investigated using a
      fluorescent dye DIOC6. The expression of caspases-3, -8, -9 and PARP was assessed
      by Western blot. The phytochemical screening of the roots of Bryonia dioica was
      performed using qualitative phytochemical standard procedures. RESULTS: The
      Bryonia dioica aqueous extract induced cell death in a dose-dependent manner. The
      IC50 of Bryonia dioica aqueous extract was estimated to be approximately 15,
      63MUg/ml. This was accompanied by induction of apoptosis, activation of caspase-3
      and -9, cleavage of PARP and loss of mitochondria membrane potential.
      Furthermore, the phytochemical screening of roots of Bryonia dioica showed the
      presence of various bioactive such as polyphenols, sterols and triterpenes,
      alkaloids, c-heterosides, carbohydrates and saponins. CONCLUSION: The aqueous
      extract of Bryonia dioica induces apoptosis in the Burkitt's lymphoma BL41 cell
      lines via the mitochondrial pathway. The flavonoids, sterols and triterpens
      detected could be responsible for the cytotoxic and apoptogenic activities of the
      aqueous extract of Bryonia dioica. These findings suggest that Bryonia dioica
      could be considered as a promising source for developing novel therapeutics
      against Burkitt's lymphoma.

PMID- 22465730
TI  - Comparing medicinal plant knowledge using similarity indices: a case of the Brou,
      Saek and Kry in Lao PDR.
AB  - BACKGROUND: Medicinal plant traditional knowledge is one of the most widely known
      traditional ecosystem services, as it provides primary healthcare, contributes to
      subsistence livelihoods, and for its potential value as a source of novel
      pharmaceuticals. People living in close contact with their surroundings for many
      generations are hypothesized to have developed, through trial-and-error, in-depth
      knowledge of ecosystems, biodiversity, and their management and utility. In the
      case of medicinal plant knowledge it could lead to an asymptotic climax or a
      constantly evolving equilibrium of cures with proven efficacy and those under
      assessment. METHODS: An in-depth study of 97 plant species used in traditional
      medicine by the Brou, Saek and Kry ethnic groups in Lao PDR was made to test
      similarity in medicinal plant knowledge. RESULTS: Medicinal plants were used in
      99 different ways in 510 species-use combinations. Medicinal uses could be
      generalized into 12 use categories with 747 species-category combinations.
      Similarity indices show Brou and Saek plant use appears to be most similar
      (QS(BS): 60.0; JI(BS): 75.1) followed by Kry and Saek (QS(KS): 51.6; JI(KS):
      53.4), and then Kry and Brou (QS(BK): 46.9; JI(BK): 44.1). DISCUSSION:
      Intercultural similarities found are quite low, considering that all three groups
      share the same geographical and ecological area and have the same dependence on
      medicinal plants. Intercultural transmission is unimpeded but many treatments are
      likely to be ineffective. Comparison of the similarities found here with
      similarities computed from other data show that these results are homologous with
      other sympatric ethnic groups, and much higher than those for allopatrically
      living groups. CONCLUSION: Medicinal plant knowledge does not reach a stable
      climax, but appears to evolve continually by trial-and-error, as effective cures
      to many ailments are unavailable.

PMID- 22465731
TI  - Evaluation of the wound healing potential of Wedelia trilobata (L.) leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Wedelia trilobata (L.) Hitchc (Asteraceae) leaves
      are used in the treatment of wounds by traditional healers. Despite the use of
      this plant in wound healing, there is a scarcity of scientific data to support
      its therapeutic application. AIM OF THE STUDY: To investigate the wound healing
      potential of Wedelia trilobata (L.) leaves commonly employed by traditional
      healers and to clarify its traditional use in a scientific investigation.
      MATERIALS AND METHODS: An ethanolic extract of Wedelia trilobata leaves was
      subjected to column chromatography. Hexane, ethyl acetate (WEA) and
      chloroform:methanol (50:50) (WCM) fractions were obtained. The fractions were
      tested using relevant in vitro wound healing assays. Antioxidant activity was
      measured by the DPPH assay. The fibroblast proliferation, oxidative stress using
      hydrogen peroxide, an in vitro scratch assay, and increasing collagen content was
      determined using fibroblast L929. Minimum inhibitory concentrations (MICs) were
      determined against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia
      coli, and Pseudomonas aeruginosa. RESULTS: WEA (3 MUg/mL) promoted fibroblast
      L929 survivability up to more than 90% before and more than 85% after hydrogen
      peroxide induced oxidative stress. WEA (3 MUg/mL) induced a 70% migration rate in
      the in vitro scratch assay and the collagen content was increased to 261 MUg/mL
      compared to the control (57.5 MUg/mL). WCM exhibited a scavenging activity for
      DPPH with an IC(50) value of 179.5 MUg/mL comparable to BHT (139.3 MUg/mL). WEA
      was active against gram positive bacteria Staphylococcus aureus, Staphylococcus
      epidermidis with MIC values of 62.5 and 31.25 MUg/mL, respectively. CONCLUSION:
      These scientific findings of wound healing activity supports the traditional
      claims for Wedelia trilobata (L.) leaves. The WEA displayed antibacterial and
      fibroblast stimulatory activities while WCM exhibited antioxidant to indicate its
      potential wound healing properties. However further studies to isolate the
      antibacterial, antioxidant and fibroblast stimulatory compounds that contribute
      to the wound healing properties of this plant are needed.

PMID- 22465733
TI  - Mechanism of dehydroxylation temperature decrease and high temperature phase
      transition of coal-bearing strata kaolinite intercalated by potassium acetate.
AB  - The thermal decomposition and dehydroxylation process of coal-bearing strata
      kaolinite-potassium acetate intercalation complex (CSKK) has been studied using X
      ray diffraction (XRD), infrared spectroscopy (IR), thermal analysis, mass
      spectrometric analysis and infrared emission spectroscopy. The XRD results showed
      that the potassium acetate (KAc) have been successfully intercalated into coal
      bearing strata kaolinite with an obvious basal distance increase of the first
      basal peak, and the positive correlation was found between the concentration of
      intercalation regent KAc and the degree of intercalation. As the temperature of
      the system is raised, the formation of KHCO(3), KCO(3) and KAlSiO(4), which is
      derived from the thermal decomposition or phase transition of CSKK, is observed
      in sequence. The IR results showed that new bands appeared, the position and
      intensities shift can also be found when the concentration of intercalation agent
      is raised. The thermal analysis and mass spectrometric analysis results revealed
      that CSKK is stable below 300 degrees C, and the thermal decomposition products
      (H(2)O and CO(2)) were further proved by the mass spectrometric analysis. A
      comparison of thermal analysis results of original coal-bearing strata kaolinite
      and its intercalation complex gives new discovery that not only a new mass loss
      peak is observed at 285  degrees C, but also the temperature of dehydroxylation
      and dehydration of coal bearing strata kaolinite is decreased about 100  degrees
      C. This is explained on the basis of the interlayer space of the kaolinite
      increased obviously after being intercalated by KAc, which led to the interlayer
      hydrogen bonds weakened, enables the dehydroxylation from kaolinite surface more
      easily. Furthermore, the possible structural model for CSKK has been proposed,
      with further analysis required in order to prove the most possible structures.

PMID- 22465732
TI  - Mycobacterium ulcerans causes minimal pathogenesis and colonization in medaka
      (Oryzias latipes): an experimental fish model of disease transmission.
AB  - Mycobacterium ulcerans causes Buruli ulcer in humans, a progressive ulcerative
      epidermal lesion due to the mycolactone toxin produced by the bacterium.
      Molecular analysis of M. ulcerans reveals it is closely related to Mycobacterium
      marinum, a pathogen of both fish and man. Molecular evidence from diagnostic PCR
      assays for the insertion sequence IS2404 suggests an association of M. ulcerans
      with fish. However, fish infections by M. ulcerans have not been well documented
      and IS2404 has been found in other mycobacteria. We have thus, employed two
      experimental approaches to test for M. ulcerans in fish. We show here for the
      first time that M. ulcerans with or without the toxin does not mount acute or
      chronic infections in Japanese Medaka "Oryzias latipes" even at high doses.
      Moreover, M. ulcerans-infected medaka do not exhibit any visible signs of
      infection nor disease and the bacteria do not appear to replicate over time. In
      contrast, similar high doses of the wild-type M. marinum or a mycolactone
      producing M. marinum "DL" strain are able to mount an acute disease with
      mortality in medaka. Although these results would suggest that M. ulcerans does
      not mount infections in fish we have evidence that CLC macrophages from goldfish
      are susceptible to mycolactones.

PMID- 22465734
TI  - Pitch reduction lithography by pressure-assisted selective wetting and thermal
      reflow.
AB  - We report on a new pitch reduction lithographic technique by utilizing pressure
      assisted selective wetting and thermal reflow. The primary line-and-space pattern
      of low molecular weight polystyrene (PS) (Mw=17,300) was formed by solvent
      assisted capillary force lithography (CFL), on which a diluted photoresist (PR)
      solution was selectively filled into the spaces by the application of a slight
      pressure (200 g cm(-2)). Subsequent removal of the PS pattern by toluene and
      ashing process led to a line pattern with approximately 50% pitch reduction. It
      was observed that the size reduction and space to width ratios were controllable
      by changing PR concentration and ashing time.

PMID- 22465735
TI  - Investigations of surfactant effects on gas hydrate formation via infrared
      spectroscopy.
AB  - This infrared (IR) spectroscopic study addresses surfactant effects on
      cyclopentane (CP) hydrate-water interfaces by observing both ice-like (3100 cm(
      1)) and water-like (3400 cm(-1)) bands in the bonded OH region together with free
      OH bands. IR spectroscopy of hydrates has not been actively employed due to the
      overwhelming signal saturation of the OH bonding. However, this work is able to
      utilize this large signal of the OH bonding to understand the water structure
      changes upon adding sodium dodecyl sulfate (SDS) to CP hydrate-water interfaces.
      The spectral data suggest a change to more ice like (3100 cm(-1)) features
      starting from 100 ppm to 750 ppm SDS, indicating favorable nucleation. At the
      same instance, water like (3400 cm(-1)) features are also shown in this range of
      SDS concentration, which suggests looser hydrogen bonding that is an indicator
      for facilitating hydrate growth. Additionally, this ATR-IR study firstly
      identifies both symmetric and anti-symmetric free OH bands of the hydrogen bond
      (HB) acceptors in the clathrate hydrate system. Relative area ratios of free and
      bonded OH bands provide important information about spatial arrangements of
      adsorbed SDS monomers.

PMID- 22465736
TI  - Two programs focused on mentoring and training in vaccine safety.

PMID- 22465737
TI  - Ascaris suum enolase is a potential vaccine candidate against ascariasis.
AB  - Ascariasis caused by Ascaris is the most common parasite problem in humans and
      pigs worldwide. No vaccines are available for the prevention of Ascaris
      infections. In the present study, the gene encoding Ascaris suum enolase (As-enol
      1) was amplified, cloned and sequenced. Amino acid sequence alignment indicated
      that As-enol-1 was highly conserved between different nematodes and shared the
      highest identity (87%) with enolase from Anisakis simplex s.l. The recombinant
      pVAX-Enol was successfully expressed in Marc-145 cells. The ability of the pVAX
      Enol for inducing immune protective responses against challenge infection with A.
      suum L3 was evaluated in Kunming mice. The immune response was evaluated by
      lymphoproliferative assay, cytokine and antibody measurements, and the reduction
      rate of recovery larvae. The results showed that the mice immunized with pVAX
      Enol developed a high level of specific antibody responses against A. suum, a
      strong lymphoproliferative response, and significant levels of IFN-gamma, IL-2,
      IL-4 and IL-10 production, compared with the other groups immunized with empty
      plasmid or blank controls, respectively. There was a 61.13% reduction (P<0.05) in
      larvae recovery compared with that in the blank control group. Our data indicated
      that A. suum enolase is a potential vaccine candidate against A. suum infection.

PMID- 22465738
TI  - A revolution in HCV treatment with direct-acting antivirals: from non-response to
      eradication.

PMID- 22465739
TI  - Cell polarity proteins and cancer.
AB  - Cell polarity is essential in many biological processes and required for
      development as well as maintenance of tissue integrity. Loss of polarity is
      considered both a hallmark and precondition for human cancer. Three conserved
      polarity protein complexes regulate different modes of polarity that are
      conserved throughout numerous cell types and species. These complexes are the
      Crumbs, Par and Scribble complex. Given the importance of cell polarity for
      normal tissue homeostasis, aberrant polarity signaling is suggested to contribute
      to the multistep processes of human cancer. Most human cancers are formed from
      epithelial cells. Evidence confirming the roles for polarity proteins in
      different phases of the oncogenic trajectory comes from functional studies using
      mammalian cells as well as Drosophila and zebrafish models. Furthermore, several
      reports have revealed aberrant expression and localization of polarity proteins
      in different human tumors. In this review we will give an overview on the current
      data available that couple polarity signaling to tumorigenesis, particularly in
      epithelial cells.

PMID- 22465740
TI  - Mycangial fungus benefits the development of a leaf-rolling weevil, Euops
      chinesis.
AB  - While a wide array of insects form symbiotic relationships with microbes, the
      underlying mechanisms of these relationships are various and complex. In this
      study, we investigated the role that the mycangial fungus Penicillium herquei
      plays in the development of the leaf-rolling weevil Euops chinesis, which feeds
      on the knotweed Fallopia japonica. The weevil inoculates the fungus during
      oviposition into a leaf-roll that it creates for its larvae. We found that
      removal of P. herquei inocula from leaf-rolls significantly decreased the
      weevil's survival rate especially in the larval stage. Although inoculation with
      P. herquei had no effect on the plant's lignin content, it significantly
      decreased the cellulose content of the knotweed leaves. P. herquei also showed
      antibiotic properties against two fungi (Rhizopus sp.) that attack the weevil's
      leaf-rolls. Our results suggest that the mycangial fungus may help alter leaf
      chemical components and protect against pathogens thus improve leaf-rolls for the
      development of E. chinesis.

PMID- 22465741
TI  - RNAi-mediated knockdown of Shade negatively affects ecdysone-20-hydroxylation in
      the desert locust, Schistocerca gregaria.
AB  - A major breakthrough in elucidating the ecdysteroid biosynthetic pathway in
      insects was realized with the molecular identification and further functional
      characterization of the 'Halloween' genes. These genes were found to encode
      cytochrome P450 enzymes catalysing the final steps of ecdysteroid biosynthesis in
      the dipteran, Drosophila melanogaster, and in the Lepidoptera, Manduca sexta and
      Bombyx mori. A recent report focused on the identification of Halloween orthologs
      in the desert locust, Schistocerca gregaria, a member of the hemimetabolous
      insect order of the Orthoptera. In the present study, an additional Halloween
      gene Shade, is identified in the desert locust. In Diptera and Lepidoptera, this
      gene encodes a 20-hydroxylase, catalysing the conversion of ecdysone (E) to 20
      hydroxyecdysone (20E). However, this enzymatic function has previously been
      suggested for CYP6H1 in another locust species, the migratory locust, Locusta
      migratoria. Using q-RT-PCR, the spatial and temporal transcript profiles of S.
      gregaria orthologs for Shade as well as CYP6H1 were analysed in last larval stage
      desert locusts. An RNA interference (RNAi)-based approach was employed to study
      whether these genes could possibly encode a functional 20-hydroxylase in the
      desert locust.

PMID- 22465742
TI  - Single DNA molecule denaturation using laser-induced heating.
AB  - This paper proposes targeted in situ denaturation through laser-induced heating
      to partially amplify relevant sequences from a long DNA strand. It uses 5 kb of
      DNA as a sample, labeling both strands with quantum dots, with one strand
      immobilized on a solid surface. We irradiated a targeted DNA sequence with a
      focused infrared laser to elevate its temperature, monitoring the process by
      microscope. The denaturation was detected in real time by separating quantum dots
      on each strand. Results showed that complete separation of the strands occurred
      within a few seconds of laser irradiation, which raised the temperature to
      approximately 90  degrees C.

PMID- 22465744
TI  - A DNA oligomer containing 2,2,4-triamino-5(2H)-oxazolone is incised by human
      NEIL1 and NTH1.
AB  - The nucleobase derivative, 2,2,4-triamino-5(2H)-oxazolone (Oz), is an oxidation
      product of guanine or of 8-oxo-7,8-dihydroguanine that causes G-to-C
      transversions in DNA. Human NEIL1 (hNEIL1) and NTH1 (hNTH1) are homologues of two
      prokaryotic base excision repair enzymes, FPG/NEI and NTH, respectively. Here, we
      demonstrated that hNEIL1 and hNTH1 cleave Oz sites as efficiently as 5
      hydroxyuracil sites. Thus, hNEIL1 and hNTH1 can repair Oz lesions. Furthermore,
      the nicking activities of these enzymes are largely independent of nucleobases
      opposite Oz; this finding indicates that removing Oz from Oz:G and Oz:A base
      pairs might cause an increase in the rate of point mutations in human cells.

PMID- 22465743
TI  - Prefrontal rTMS for treating depression: location and intensity results from the
      OPT-TMS multi-site clinical trial.
AB  - BACKGROUND: Motor cortex localization and motor threshold determination often
      guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings
      for non-motor brain stimulation. However, anatomic variability results in
      variability of placement and effective intensity. OBJECTIVE: Post-study analysis
      of the OPT-TMS Study reviewed both the final positioning and the effective
      intensity of stimulation (accounting for relative prefrontal scalp-cortex
      distances). METHODS: We acquired MRI scans of 185 patients in a multi-site trial
      of left prefrontal TMS for depression. Scans had marked motor sites (localized
      with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm
      rule"). Based on a visual determination made before the first treatment, TMS
      therapy occurred either at the 5 cm location or was adjusted 1 cm forward.
      Stimulation intensity was 120% of resting motor threshold. RESULTS: The "5 cm
      rule" would have placed stimulation in premotor cortex for 9% of patients, which
      was reduced to 4% with adjustments. We did not find a statistically significant
      effect of positioning on remission, but no patients with premotor stimulation
      achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor
      threshold, and no seizures were induced across this range. Patients experienced
      remission with effective stimulation intensity ranging from 93 to 146% of motor
      threshold, and we did not find a significant effect of effective intensity on
      remission. CONCLUSIONS: Our data indicates that individualized positioning
      methods are useful to reduce variability in placement. Stimulation at 120% of
      motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad
      range of patients.

PMID- 22465745
TI  - The hypoxic environment reprograms the cytokine/chemokine expression profile of
      human mature dendritic cells.
AB  - Myeloid dendritic cells (DCs) are professional antigen-presenting cells critical
      for the orchestration of immunity and maintenance of self-tolerance. DC
      development and functions are tightly regulated by a complex network of
      inhibitory and activating signals present in the tissue microenvironment, and
      dysregulated DC responses may result in amplification of inflammation, loss of
      tolerance, or establishment of immune escape mechanisms. Generation of mature
      (m)DCs from monocytic precursors recruited at pathological sites occurs under
      condition of low partial oxygen pressure (pO(2)). However, the way in which the
      hypoxic microenvironment modulates the functions of these cells is still not
      clear. We demonstrate that chronic hypoxia (4 days, 1% O(2)) promotes the onset
      of a highly proinflammatory gene expression profile in mDCs generated from
      primary human monocytes, characterized by the modulation of a significant cluster
      of genes coding for proinflammatory chemokines/cytokines and/or their receptors.
      Within the chemokine system, strong upregulation of genes encoding proteins
      chemotactic for neutrophils, such as CXCL2, CXCL3, CXCL5, CXCL6, and CXCL8, and
      for activated/memory T lymphocytes, monocytes, and immature (i) DCs, e.g. CCL20,
      CCL3 and CCL5, was observed, concomitant with decreased expression of genes
      coding for naive/resting T cells chemoattractants, CCL18 and CCL23. Other hypoxia
      inducible genes coded for cytokines with a primary role in inflammation and
      angiogenesis, including osteopontin, vascular endothelial growth factor, and IL
      1beta. mRNA modulation was paralleled by protein secretion. These results suggest
      that conditions of reduced O(2) availability reprograms mDCs toward a
      proinflammatory direction by tuning the cytokine/chemokine repertoire, thus
      affecting their ability to regulate leukocyte trafficking and activation at
      pathological sites, with potential implications for the pathogenesis of chronic
      inflammatory diseases.

PMID- 22465746
TI  - Production and characterization of mammalian virus-like particles from modified
      vaccinia virus Ankara vectors expressing influenza H5N1 hemagglutinin and
      neuraminidase.
AB  - Several studies have described the production of influenza virus-like particles
      (VLP) using a variety of platform systems. These VLPs are non-replicating
      particles that spontaneously self-assemble from expressed influenza virus
      proteins and have been proposed as vaccine candidates for both seasonal and
      pandemic influenza. Although still in the early stages of development and
      evaluation as influenza vaccines, influenza VLPs have a variety of other valuable
      uses such as examining and understanding correlates of protection against
      influenza and investigating virus-cell interactions. The most common production
      system for influenza VLPs is the baculovirus-insect cell expression which has
      several attractive features including the ease in which new gene combinations can
      be constructed, the immunogenicity elicited and protection afforded by the
      produced VLPs, and the scalability offered by the system. However, there are
      differences between the influenza VLPs produced by baculovirus expression systems
      in insect cells and the influenza viruses produced for use as current vaccines or
      the virus produced during a productive clinical infection. We describe here the
      development of a modified vaccinia virus Ankara (MVA) system to generate
      mammalian influenza VLPs containing influenza H5N1 proteins. The MVA vector
      system is flexible for manipulating and generating various VLP constructs,
      expresses high level of influenza hemagglutinin (HA), neuraminidase (NA), and
      matrix (M) proteins, and can be scaled up to produce VLPs in quantities
      sufficient for in vivo studies. We show that mammalian VLPs are generated from
      recombinant MVA vectors expressing H5N1 HA alone, but that increased VLP
      production can be achieved if NA is co-expressed. These mammalian H5N1 influenza
      VLPs have properties in common with live virus, as shown by electron microscopy
      analysis, their ability to hemagglutinate red blood cells, express neuraminidase
      activity, and to bind influenza specific antibodies. Importantly, these VLPs are
      able to elicit a protective immune response in a mouse challenge model,
      suggesting their utility in dissecting the correlates of immunity in such models.
      Mammalian derived VLPs may also provide a useful tool for studying virus-cell
      interactions and may have potential for development as pandemic vaccines.

PMID- 22465747
TI  - Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same
      protection against the murine model of leishmaniasis.
AB  - First generation Leishmania vaccines consisting of whole killed parasites with or
      without adjuvants have reached phase 3 trial and failed to show enough efficacy
      mainly due to the lack of an appropriate adjuvant. In this study, the nuclease
      resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease
      sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance
      immunogenicity and rate of protection against leishmaniasis. Due to the
      susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery
      system was developed to protect them from degradation. 1, 2-dioleoyl-3
      trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its
      unique adjuvanticity and electrostatic interaction with negatively charged CpG
      ODNs. To evaluate the role of liposomal formulation in protection rate and
      enhanced immune response, BALB/c mice were immunized subcutaneously with
      liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA
      PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for
      protection, footpad swelling at the site of challenge, parasite loads, the levels
      of IFN-gamma and IL-4, and the IgG subtypes were evaluated. The groups of mice
      receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared
      with the control groups. In addition, there was no significant difference in
      immune response generation between mice immunized with PS CpG and the group
      receiving PO CpG when incorporated into the liposomes. The results suggested that
      liposomal form of PO CpG might be used instead of PS CpG in future vaccine
      formulations as an efficient adjuvant.

PMID- 22465749
TI  - Antibody repertoire development in fetal and neonatal piglets. XXIII: fetal
      piglets infected with a vaccine strain of PRRS Virus display the same immune
      dysregulation seen in isolator piglets.
AB  - The Ig levels and antibody repertoire diversification in fetal piglets infected
      with an attenuated Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)
      were measured. Serum Ig levels were greatly elevated in PRRSV-infected fetuses;
      IgG was elevated >50-fold, IgM>5-15-fold and IgA>2-fold compared to control
      fetuses. Their IgM to IgG to IgA profile was the same as that in isolator piglets
      infected for the same period with wild-type PRRSV. Fetal animals showed less
      repertoire diversification than even isolator piglets that were maintained
      germfree (GF) while the repertoire diversification index (RDI) for PRRSV-infected
      isolator piglets was 10-fold higher and comparable to littermates infected with
      swine influenza (S-FLU). However, when expressed as the RDI:Ig ratio, infected
      fetuses appeared 10-fold less capable of repertoire diversification than
      uninfected littermates and GF isolator piglets. Compared to S-FLU isolator
      piglets that resolve the infection, the RDI:Ig of PRRSV-infected isolator piglets
      was 100-fold lower. Overall, infection of fetuses with an attenuated virus shows
      the same immune dysregulation seen postnatally in wild type infected isolator
      piglets, indicating that: (a) attenuation did not alter the ability of the virus
      to cause dysregulation and (b) the isolator infectious model reflects the fetal
      disease.

PMID- 22465748
TI  - A virus-like particle vaccine platform elicits heightened and hastened local lung
      mucosal antibody production after a single dose.
AB  - We show that a model antigen, ovalbumin (OVA), can be chemically conjugated to
      the exterior of a small heat shock protein (sHsp) cage that has structural
      similarities to virus-like particles (VLPs). OVA-sHsp conjugation efficiency was
      dependent upon the stoichiometry and the length of the small molecule linker
      utilized, and the attachment position on the sHsp cage. When conjugated OVA-sHsp
      was delivered intranasally to naive mice, the resulting immune response to OVA
      was accelerated and intensified, and OVA-specific IgG1 responses were apparent
      within 5 days after a single immunizing dose, illustrating its utility for
      vaccine development. If animals were pretreated with a disparate VLP, P22 (a non
      replicative bacteriophage capsid), before OVA-sHsp conjugate immunization, OVA
      specific IgG1 responses were apparent already by 4 days after a single immunizing
      dose of conjugate in OVA-naive mice. Additionally, the mice pretreated with P22
      produced high titer mucosal IgA, and isotype-switched OVA-specific serum IgG.
      Similarly, sHsp pretreatment enhanced the accumulation of lung germinal center B
      cells, T follicular helper cells, and increased polymeric Ig receptor expression,
      priming the lungs for subsequent IgG and IgA responses to influenza virus
      challenge. Thus, sHsp nanoparticles elicited quick and intense antibody responses
      and these accelerated responses could similarly be induced to antigen chemically
      conjugated to the sHsp. Pretreatment of mice with P22 further accelerated the
      onset of the antibody response to OVA-sHsp, demonstrating the utility of
      conjugating antigens to VLPs for pre-, or possibly post-exposure prophylaxis of
      lung, all without the need for adjuvant.

PMID- 22465750
TI  - A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella
      typhi.
AB  - Pneumococcal and Salmonella typhi infections are two major diseases for children
      in developing countries. For typhoid fever, licensed Vi polysaccharide vaccines
      are ineffective in children <2-year old. While investigational Vi conjugate
      vaccines have been shown effective in clinical trials, they are currently only
      available to restricted areas. Pneumococcal capsular polysaccharide conjugate
      vaccines are highly effective in children, but suffer from some limitations
      including cost and limited serotype coverage. We have previously shown that a
      fusion conjugate vaccine, consisting of pneumococcal fusion protein PsaA and
      pneumolysoid (PdT) conjugated to a polysaccharide, results in enhanced antibody
      and CD4+ Th17 cell responses as well as protection against pneumococcal
      colonization and disease in mice. Here we applied this approach to develop a
      bivalent vaccine against pneumococcus and S. typhi. Two species-conserved
      pneumococcal antigens (SP1572 or SP2070) were fused to the nonhemolytic
      pneumolysoid PdT. SP1572-PdT was then conjugated to Vi polysaccharide and SP2070
      PdT was conjugated to the pneumococcal cell wall polysaccharide (CWPS; also
      conserved). Mice immunized with this bivalent conjugate were protected against
      pneumococcal colonization and sepsis challenges, and made anti-Vi antibody
      concentrations higher by 40-fold compared to mice that received equimolar
      mixtures of the antigens. An enhanced killing of Vi-bearing Salmonellae in vitro
      was demonstrated from plasma of mice that received the fusion conjugate but not
      the mixture of antigens. Our results support further evaluation of this bivalent
      immunogen for the prevention of pneumococcal colonization and disease, and of
      typhoid fever.

PMID- 22465751
TI  - Urticaria pigmentosa in a female patient with celiac disease: response to a
      gluten-free diet.

PMID- 22465752
TI  - IP-10 is an additional marker for tuberculosis (TB) detection in HIV-infected
      persons in a low-TB endemic country.
AB  - OBJECTIVE: In Indian HIV-infected patients, IP-10 response to QuantiFERON-TB Gold
      In tube (QFT-IT) antigens has been associated to tuberculosis (TB). However,
      specificity for active TB was lower than that reported by QFT-IT, making accuracy
      for TB detection questionable. To investigate this uncertainty, likely due to
      India being highly endemic for TB, and to better identify TB correlates, we
      evaluated the IP-10-based assay in HIV-infected subjects in Italy, a low-TB
      endemic country. METHODS: 195 individuals were prospectively enrolled; 118 were
      HIV-infected (21 with active TB, 97 without active TB, and distinguished as
      high/low-TB-risk). QFT-IT was performed and IP-10 was evaluated by ELISA.
      RESULTS: Among the HIV-infected individuals, sensitivity for active TB was 66.7%
      by IP-10-based test and 52.4% (p = 1) by QFT-IT. IP-10-based assay showed a lower
      dependence on mitogen-response and CD4 counts than QFT-IT. Among subjects without
      active TB, a higher proportion of IP-10 responders was shown in high-TB-risk
      subjects than low-TB-risk subjects (40.0% vs 12.9%), similar to QFT-IT (37.1% vs
      4.8%). Low-TB risk subjects showed 87.1% specificity for active TB by IP-10-based
      test vs 95.2% by QFT-IT. CONCLUSIONS: In a low-TB endemic country, besides IFN
      gamma, IP-10 response to QFT-IT is associated with active TB and TB risk factors
      in HIV-infected patients with lower dependence on mitogen-response and CD4
      counts.

PMID- 22465754
TI  - Plume characteristics and dynamics of UV and IR laser-desorbed oligonucleotides.
AB  - Laser desorption of dye-tagged oligonucleotides was studied using laser-induced
      fluorescence imaging. Desorption with ultra violet (UV) and infra-red (IR) lasers
      resulted in forward directed plumes of molecules. In the case of UV desorption,
      the initial shot desorbed approximately seven-fold more material than subsequent
      shots. In contrast, the initial shot in IR desorption resulted in the ejection of
      less material compared to subsequent shots and these plumes had a component
      directed along the path of the laser. Thermal equilibrium of the molecules in the
      plume was achieved after approximately 25 MUs with a spread in molecular
      temperature which was described by a modified Maxwell-Boltzmann equation.

PMID- 22465753
TI  - Lysophosphatidic acid induces lymphangiogenesis and IL-8 production in vitro in
      human lymphatic endothelial cells.
AB  - The bioactive phospholipid lysophosphatidic acid (LPA) and its receptors LPA(1-3)
      are aberrantly expressed in many types of human cancer. LPA has been reported to
      induce tumor cell proliferation, migration, and cytokine production. However,
      whether LPA exerts an effect on lymphatic endothelial cells (LECs) or on
      lymphangiogenesis, a process of new lymphatic vessel formation that is associated
      with increased metastasis and poor prognosis in cancer patients, has been
      unknown. Here, we show that LPA induces cell proliferation, survival, migration,
      and tube formation, and promotes lymphangiogenesis in vitro in human dermal LECs.
      In addition, LPA induces IL-8 expression by enhancing IL-8 promoter activity via
      activation of the NF-kappaB pathway in LECs. Using IL-8 siRNA and IL-8
      neutralizing antibody, we revealed that IL-8 plays an important role in LPA
      induced lymphangiogenesis in vitro. Moreover, using siRNA inhibition, we
      discovered that LPA-induced lymphangiogenesis in vitro and IL-8 production are
      mediated via the LPA(2) receptor in LECs. Finally, using human sentinel afferent
      lymphatic vessel explants, we demonstrated that LPA up-regulates IL-8 production
      in the LECs of lymphatic endothelia. These studies provide the first evidence
      that LPA promotes lymphangiogenesis and induces IL-8 production in LECs; we also
      reveal a possible new role of LPA in the promotion of tumor progression, as well
      as metastasis, in different cancer types.

PMID- 22465755
TI  - Cytotoxicity and biocompatibility evaluation of N,O-carboxymethyl
      chitosan/oxidized alginate hydrogel for drug delivery application.
AB  - In this paper, covalently cross-linked hydrogel composed of N,O-carboxymethyl
      chitosan and oxidized alginate was developed intending for drug delivery
      application. In vitro/vivo cytocompatibility and biocompatibility of the
      developed hydrogel were preliminary evaluated. In vitro cytocompatibility test
      showed that the developed hydrogel exhibited good cytocompatibility against NH3T3
      cells after 3-day incubation. According to the results of acute toxicity test,
      there was no obvious cytotoxicity for major organs during the period of 21-day
      intraperitoneal administration. Meanwhile, the developed hydrogel did not induce
      any cutaneous reaction within 72 h of subcutaneous injection followed by slow
      degradation and adsorption with the time evolution. Moreover, the extraction of
      developed hydrogel had nearly 0% of hemolysis ratio, which indicated the good
      hemocompatibility of hydrogel. Based on the above results, it may be concluded
      that the developed N,O-carboxymethyl chitosan/oxidized alginate hydrogel with non
      cytotoxicity and good biocompatibility might suitable for the various drug
      delivery applications.

PMID- 22465756
TI  - Transfusion practices.

PMID- 22465757
TI  - The effect of cholesterol levels on hematopoietic stem cell mobilization.
AB  - Data regarding effects of cholesterol levels on hematopoietic stem cell
      mobilization are limited. We retrospectively reviewed the relationship between
      serum total cholesterol levels and peripheral blood CD34 (PBCD34) cell counts in
      52 granulocyte colony stimulating factor (G-CSF) induced mobilization cycles with
      or without chemotherapy. The cholesterol levels between the poor and good
      mobilization groups (median 172mg/dl vs. 183.5mg/dl, respectively, p=0.18) were
      not different. No significant correlation was obtained between the cholesterol
      levels and PBCD34 counts (r=0.02, p=0.85). No significant correlation was
      obtained between cholesterol levels and PBCD34 counts in patients neither
      mobilized with G-CSF alone (r=-0.02, p=0.9) nor G-CSF plus chemotherapy (r=0.04,
      p=0.8). The results of the study indicate that there was no effect of cholesterol
      on hematopoietic stem cell mobilization. Prospective cohort studies are needed to
      demonstrate the effect of cholesterol on mobilization and its extent in humans.

PMID- 22465758
TI  - Pre-emptive plerixafor injection increases blood neutrophil, lymphocyte and
      monocyte counts in addition to CD34+ counts in patients with non-Hodgkin lymphoma
      mobilizing poorly with chemotherapy plus G-CSF: potential implications for
      apheresis and graft composition.
AB  - BACKGROUND: CXCR4 receptor antagonist plerixafor is used to mobilize
      hematopoietic stem cells. No detailed data regarding the effects of plerixafor on
      other blood cell components have been published but may be of importance in
      regard to graft composition collected after plerixafor injection. PATIENTS AND
      METHODS: The study included thirty-nine patients with non-Hodgkin lymphoma (NHL)
      mobilized with chemotherapy plus G-CSF. Plerixafor was given pre-emptively in
      twenty patients due to poor mobilization or low collection yield. Nineteen NHL
      patients served as controls. We evaluated CD34(+) counts and WBC counts and
      differential from the morning of the first plerixafor injection and 8h after the
      plerixafor injection. From the control patients the corresponding values were
      evaluated on the morning of the first apheresis and 24h before it. RESULTS: The
      first plerixafor dose increased CD34(+) counts and number of leukocytes,
      neutrophils, lymphocytes, eosinophils and monocytes. Leukocyte, neutrophil,
      lymphocyte, monocyte and eosinophil counts were higher after plerixafor injection
      compared to the control group at the time of the first apheresis. Minimal graft
      (?2*10(6)/kg CD34(+) cells) was collected in 85% of plerixafor treated patients,
      with a single apheresis in 45% of the patients. DISCUSSION: Plerixafor
      significantly increases B-CD34(+) cell counts on the next morning making
      effective blood stem cell collection possible in the majority of the patients
      mobilizing poorly. It also influences other blood cell components but impact of
      this observation in regard to graft content and post-transplant course needs to
      be assessed in further studies.

PMID- 22465759
TI  - Contingency plan implementation.
AB  - BACKGROUND: Although the National blood system in Canada reduces the risk of
      inventory shortages the possibility of a blood supply shortage still exists. The
      Ontario Ministry of Health and Long-Term Care developed a provincial plan to
      manage blood transfusion needs and inventory in the event of a National blood
      shortage. The Ontario plan was developed to align with the National plan as well
      as other provincial plans in order to ensure consistency in blood management
      strategies across the country. The Ontario plan was released in 2008, along with
      a toolkit to aid hospitals in developing their facility specific plans. In the
      Champlain region of Ontario, a group of 16 hospitals worked collaboratively to
      develop a regional blood shortage plan. A provincial blood shortage simulation
      exercise was held in 2010 to test out these plans. METHOD: The Director of
      Transfusion Medicine of the largest facility in the group of 16 hospitals (The
      Ottawa Hospital) took the lead in the development of the regional blood shortage
      management plan. Working groups from all 16 sites contributed to the plan
      development. The proposed plan was presented to the Medical Advisory Committee
      for approval. RESULTS: The plan consists of activities relating to the severity
      of the supply shortage as defined by Amber, Red, Recovery and Green phases. The
      plan includes a communication plan for notifying stakeholders including patients
      whose treatment may be affected. Inventory management and triage guidelines are
      provided to reduce the demand for blood and to conserve inventory for those
      patients whose need is prioritized as highest. The regional blood shortage
      management plan was tested successfully during the provincial simulation
      exercise. CONCLUSION: Where regional hospitals work together to provide
      healthcare, it is beneficial to develop a standardized plan to provide guidance
      to hospital personnel in response to a blood supply shortage. A consistent plan
      will ensure patient care is provided in a consistent manner across a health
      region. Mock or simulation exercises can aid in testing plans and raising the
      awareness of stakeholders.

PMID- 22465760
TI  - Decreased soluble TGF-beta1, Tie-2, and angiopoietins serum levels in bone marrow
      after treating healthy donors with granulocyte colony-stimulating factor.
AB  - The goal of this study was to investigate the effect of granulocyte colony
      stimulating factor (G-CSF) on Tie-2, angiopoietins, VEGF, and TGF-beta1 in bone
      marrow (BM) of healthy donors. Soluble Tie-2, angiopoietins, VEGF, and TGF-beta1
      levels in the BM were determined via ELISA in 25 healthy donors before and after
      G-CSF treatment. The results showed that treating healthy donors with G-CSF
      significantly decrease serum levels of Tie-2, angiopoietin-1, angiopoietin-2, and
      TGF-beta1. In contrast, median VEGF level in the G-CSF-primed BM was
      significantly higher than steady-state BM. Our results suggest that decreased
      soluble TGF-beta1, Tie-2, and angiopoietins levels in the BM could be related to
      stem cell mobilization.

PMID- 22465761
TI  - Inpatient treatment in the psychiatric department of a German prison hospital.
AB  - OBJECTIVE: Although the construct of psychic incompetence can prevent severely
      mentally disturbed persons from being imprisoned in Germany, the prevalence of
      mentally disordered persons who are detained is high. Data describing the
      characteristics of mentally disturbed detainees in Germany are scarce. The
      following study uses data from a psychiatric care institution in a prison to
      examine the distribution of psychiatric diagnoses in relation to age, nationality
      and legal status. The distribution of diagnoses is compared to that of the
      psychiatric department at a Berlin community hospital. METHOD: The data were
      recorded during each patient's hospital treatment and summarised on the day of
      discharge. The following variables were assessed: age, length of stay in days,
      main diagnosis, up to 2 additional diagnoses, frequency of violent or suicidal
      behaviour, and nationality. Data were collected from January 2010 to February
      2011 in the psychiatric department of the Berlin Prison Hospital. RESULTS: During
      a 14-month period, 107 patients were discharged from psychiatric inpatient care
      and N=124 completed treatments were observed. Of these patients, 21.5% were pre
      trial detainees, and 58% were of German nationality. The mean age was 37.7 years.
      Non-German patients were younger than German patients. Fifty-five percent of the
      patients suffered from a psychotic disorder, and 7.5% had a main diagnosis of
      antisocial personality disorder. Personality disorders were significantly less
      frequently diagnosed in non-German patients. An additional diagnosis of substance
      abuse was present in 66% of the patients, and 17.8% of the patients showed
      suicidal and/or violent behaviour or had to be restrained (immobilisation,
      isolation, compulsory medication). The frequency of suicide, violence and
      compulsory measures did not differ significantly between German and non-German
      patients, between younger and older patients or between remand and sentenced
      inmates. The distribution of psychiatric diagnoses was similar to that of a
      Berlin community hospital. CONCLUSIONS: Personality disorders were more
      frequently diagnosed in German than in non-German patients. The burden of
      personality disorders among mentally ill prison detainees in Berlin Prison
      Hospital was not significantly higher than that of a Berlin community hospital.
      The percentage of non-German patients in the psychiatric department of the Berlin
      Prison Hospital was more than two times higher than in a psychiatric department
      of a community hospital. The lower-than-expected rate of suicide attempts among
      pre-trial detainees may be an indicator of a beneficial effect of the treatment
      setting in the psychiatric department of Berlin Prison Hospital.

PMID- 22465762
TI  - Molecular structure, spectroscopic investigations, second-order nonlinear optical
      properties and intramolecular proton transfer of (E)-5-(diethylamino)-2-[(4
      propylphenylimino)methyl]phenol: a combined experimental and theoretical study.
AB  - This work presents a combined experimental and theoretical study on an ortho
      hydroxy Schiff base compound, (E)-5-(diethylamino)-2-[(4
      propylphenylimino)methyl]phenol. The crystal structure and spectroscopic
      properties of the compound have been determined by using X-ray diffraction, IR
      and UV-vis spectroscopy techniques. The electronic structure, vibrational
      frequencies and electronic absorption spectra have been investigated from the
      calculative point of view. A relaxed potential energy surface scan has been
      performed based on the optimized geometry of OH tautomeric form to describe the
      potential energy barrier belonging to intramolecular proton transfer and to
      observe the effects of transfer on the molecular geometry. The second-order
      nonlinear optical properties have been investigated based on the first static
      hyperpolarizability (beta) by using the density functional theory.

PMID- 22465763
TI  - One new and six known triterpene xylosides from Cimicifuga racemosa: FT-IR, Raman
      and NMR studies and DFT calculations.
AB  - One new and six known triterpene xylosides were isolated from Cimicifuga racemosa
      (black cohosh, Actaea racemosa). The structure of a new compound, designated as
      isocimipodocarpaside (1), was established to be (24S)-3beta-hydroxy-24,25
      oxiirane-16,23-dione-9,10-seco-9,19-cyclolanost-1(10),7(8),9(11)-trien 3-O-beta-d
      xylopyranoside, by means of (1)H and (13)C NMR, IR and Raman spectroscopies and
      Mass Spectrometry. The six known compounds are: 23-epi-26-deoxycimicifugoside
      (2), 23-epi-26-deoxyactein (3), 25-anhydrocimigenol xyloside (4), 23-O
      acetylshengmanol xyloside (5), 25-O-acetylcimigenol xyloside (6) and 3'-O
      acetylcimicifugoside H-1 (7). On the basis of NMR data supported by DFT
      calculations of NMR shielding constants of (2), its structure, previously
      described as 26-deoxycimicifugoside was corrected and determined as 23-epi-26
      deoxycimicifugoside. The (13)C CPMAS NMR spectra of the studied compounds (1)-(7)
      provided data on their solid-state interactions. The IR and Raman spectra in the
      CO, CC, and CH stretching vibration regions clearly discriminate different
      triterpenes found in C. racemosa.

PMID- 22465764
TI  - Influence of a methyl substituent on the Raman spectrum of but-3-enyl methyl
      ether.
AB  - The Raman spectrum of but-3-enyl methyl ether, CH(2)CHCH(2)CH(2)OCH(3) is
      reported and compared with those of its homologues in which a methyl group is
      substituted for a hydrogen atom on one of the carbon atoms of the alkenyl chain.
      Attention is focused on the influence of this methyl group on the bands in the
      spectrum associated with specific CH, skeletal stretching and bending vibrations.
      The use of ab initio DFT quantum mechanical calculations to assist in making
      these assignments reveals a high degree of mode-mixing in the skeletal
      vibrations. The value of model studies of this kind in refining the correlations
      between the presence and absence of specific bands in a Raman spectrum with
      molecular structure is emphasised.

PMID- 22465765
TI  - The spectroscopic (FT-Raman, FT-IR, UV and NMR), molecular electrostatic
      potential, polarizability and hyperpolarizability, NBO and HOMO-LUMO analysis of
      monomeric and dimeric structures of 4-chloro-3,5-dinitrobenzoic acid.
AB  - Quantum chemical calculations of energies, geometrical structure and vibrational
      wavenumbers of 4-chloro-3,5-dinitrobenzoic acid (CDNBA) were carried out by using
      density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. To
      determine lowest-energy molecular conformation of the title molecule, the
      selected torsion angle is varied every 10 degrees  and molecular energy profile
      is calculated from 0 degrees  to 360 degrees . The optimized geometrical
      parameters obtained by DFT calculations are in good conformity with single
      crystal XRD data. The FT-IR and FT-Raman spectra were measured in the condensed
      state. The fundamental vibrational wavenumbers as well as their intensities were
      calculated and a good agreement between observed and scaled calculated
      wavenumbers has been achieved. The electric dipole moment, polarizability and the
      first hyperpolarizability values of the CDNBA have been calculated at the same
      level of theory and basis set. The calculation results also show that the CDNBA
      molecule may has nonlinear optical (NLO) behavior with non-zero values. Stability
      of the molecule arising from hyperconjugative interactions and charge
      delocalization has been analyzed using natural bond orbital analysis. Ultraviolet
      visible (UV) spectrum of the title molecule has also been calculated using CIS
      and TD-DFT methods. The calculated energy and oscillator strength almost exactly
      reproduce the experimental data. The (1)H and (13)C nuclear magnetic resonance
      (NMR) chemical shifts of the molecule were calculated by the gauge independent
      atomic orbital (GIAO) method and compared with experimental results. The
      thermodynamic properties of the studied compound at different temperatures were
      calculated.

PMID- 22465766
TI  - Synthesis, crystal structure, spectroscopic investigations, thermal behavior and
      DFT calculations of pentacarbonyl(2-methylpyrazine)chromium(0).
AB  - Pentacarbonyl(2-methylpyrazine)chromium(0) [Cr(CO)(5)(2mpyz)], complex was
      isolated from its n-hexane solution as orange plate-like crystals which were
      characterized by IR, NMR spectroscopies and X-ray crystallography. The
      crystallographic results show that the complex was crystallized in the monoclinic
      system with the unit cell parameters of a=7.176 (5), b=12.045 (3), c=14.461 (3)A,
      beta=90.44 (3) degrees  and space group 2/M. The single crystal structure of the
      complex shows the bonding of chromium metal to 2-methylpyrazine through the less
      sterically hindered nitrogen-4 lone pair. The pyrazine ring plane makes an angle
      of 179.58 degrees  (19) with COCrN bond axis. The four carbonyl groups are
      slightly bent away from pyrazine with the angle of 91.28 degrees  (17) for
      C(5)CrN1 bond axis. The DFT calculations run out using the Gaussian 03 PC program
      show good agreement with the experimental results. The thermal properties of the
      complex were also investigated by differential thermal analysis and
      thermogravimetry techniques.

PMID- 22465767
TI  - Luminescence properties of multilayer coated single structure ZnS/CdS/ZnS
      nanocomposites.
AB  - Water soluble ZnS, CdS and multilayer coated ZnS/CdS/ZnS nanocomposites were
      successfully synthesized by chemical method in an air atmosphere. Structural,
      morphology and optical properties were characterized by X-ray diffraction (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV
      visible absorption (UV-vis) and photoluminescence (PL) spectrometer. The obtained
      particles are highly crystalline and monodisperse with an average particle size
      of 4.3-5.6nm range. A significant red shift was observed by increasing the CdS
      thickness in ZnS/CdS/ZnS nanocomposites. The PL position of ZnS and CdS compound
      is tuned in the visible region by the way of alteration layer thickness.

PMID- 22465768
TI  - Characterization of Xenorhabdus and Photorhabdus bacteria by Fourier transform
      mid-infrared spectroscopy with attenuated total reflection (FT-IR/ATR).
AB  - The use of Fourier transform mid-infrared spectroscopy with attenuated total
      reflection for characterizing entomopathogenic bacteria from genera Xenorhabdus
      and Photorhabdus is evaluated for the first time. The resulting spectra of
      Xenorhabdus poinarii and Photorhabdus luminiscens were compared with the spectrum
      of Escherichia coli samples. The absorption spectra generated by the bacteria
      samples, were very different at the region below 1400cm(-1) which represents the
      stretching vibrations of phosphate and carbohydrates. Star diagrams of the
      fingerprint section of nematodes spectra (between 1,350 and 1,650 cm(-1)) for
      separation between spectra was used and showed to be a useful tool for
      classification purposes.

PMID- 22465769
TI  - Vibrational spectroscopy and electrophoresis as a "golden means" in monitoring of
      polysaccharides in medical plant and gels.
AB  - In recent years, some bioactive polysaccharides isolated from natural sources
      have attracted much attention in the field of biochemistry and pharmacology. Of
      them, polysaccharides or their glycoconjugates were shown to exhibit multiple
      biological activities including anticarcinogenic, anticoagulant,
      immunostimulating, antioxidant, etc. Pharmacotherapy using plant-derived
      substances can be currently regarded as a very promising future alternative to
      conventional therapy. The advanced biotechnologies available today enable
      chemical investigation of well-defined bioactive plant components as sources of
      novel drugs. The need for safer drugs without side effects has led to the use of
      natural ingredients with proven safety. Special interest is focused on plant
      polysaccharides. This article attempts to review the current structural and
      conformational characterization of some importantly bioactive monosaccharides
      isolated from following plant cell-wall: Symphytum officinale (comfrey), Thymus
      pulegioides (thyme), Trigonella foenum-graecum L. (fenugreek), Tussilago farfara
      L. (coltsfoot), Hyssopus officinalis (hyssop), Althaea officinalis L.
      (marshmallow) and Equisetum arvense L. (horsetail). The chemical structures of
      monosaccharides were analysed using FTIR and Raman spectroscopies as well as
      cellulose acetate membrane electrophoresis (CAE). The dried plant samples were
      gently hydrolysed with sulphuric acid. The presence of glucuronic acid,
      galacturonic acid, alginic acid, glucose, mannose and xylose in the hydrolysates
      of reference substances and non-defatted plant films was proved. The possibility
      of a taxonomic classification of plant cell walls based on infrared and Raman
      spectroscopies and the use of spectral fingerprinting for authentication and
      detection of adulteration of products rich in cell-wall materials are discussed.
      Individual bands were selected to monitor the sugar content in medical plant cell
      walls and to confirm the identity of the analysed plants.

PMID- 22465770
TI  - Synthesis and optical characterization of single phased ZnS:Mn2+/CdS core-shell
      nanoparticles.
AB  - Uncoated ZnS, ZnS:Mn(2+), CdS and different thickness of CdS coated ZnS:Mn(2+)
      core-shell nanoparticles were successfully synthesized by a simple chemical
      method in an air atmosphere. X-ray diffraction (XRD) and transmission electron
      microscopy (TEM) techniques were used to characterize the uncoated and the novel
      ZnS:Mn(2+)/CdS core-shell nanoparticles. The results show that the size of the
      ZnS:Mn(2+)/CdS core-shell nanoparticles is less than the bare ZnS:Mn(2+). The PL
      study of ZnS:Mn(2+)/CdS core-shell nanoparticles shows an enhanced intensity than
      ZnS:Mn(2+). The coating of CdS layer over ZnS:Mn(2+) tuned the PL emission in the
      visible region. Addition of cadmium acetate (Cd 4 and 5M) in ZnS:Mn(2+) shows a
      distinct PL peak centered at 542 nm. The presence of Mn(2+) ions in ZnS lattice
      and the growth of the CdS on ZnS:Mn(2+) nanoparticles were confirmed by the ESR
      spectra.

PMID- 22465771
TI  - Optical, elemental and structural analyses of acetoacetanilide single crystals
      for nonlinear optical applications.
AB  - Single crystals of acetoacetanilide have been successfully grown by slow
      evaporation solution growth method at room temperature. The grown crystal belongs
      to orthorhombic crystal system having the lattice dimensions of a=8.686A,
      b=11.104A, c=19.232A. Its crystalline perfection was examined by home-made high
      resolution X-ray diffractometer (HRXRD), and found that that the quality of the
      specimen is reasonable. The presence of carbon, hydrogen and nitrogen were
      experimentally determined by elemental analysis and that are in good agreement
      with the theoretically calculated values. Its laser damage threshold, phase
      matching and second harmonic generation efficiency were determined by using
      Nd:YAG laser as a source. Optical behavior of acetoacetanilide was examined by
      using photoluminescence studies. Its hyerpolarizability and HOMO-LUMO energies
      were calculated by using density functional theory (DFT).

PMID- 22465772
TI  - Synthesis, growth and characterization of a new nonlinear optical crystal:
      glycinium hydrogen squarate (GHS).
AB  - Single crystals of glycinium hydrogen squarate (GHS) have been successfully
      synthesized and purity of the material has been increased by repeated
      recrystallization process. Single crystals were grown by slow evaporation
      solution growth technique using water and ethanol as solvents at room
      temperature. Then the grown crystal was characterized by different techniques for
      finding its suitability for device fabrications. The grown crystal was
      characterized by single crystal XRD, powder XRD, FT-IR, UV-Vis-NIR, (1)H NMR,
      (13)C NMR, SHG and DTA/TGA analyses respectively. From the single crystal XRD
      diffraction, the crystal system was identified as monoclinic. The presence of
      functional groups were identified by FT-IR analysis. The UV transparency cut-off
      wavelength of the grown crystal occurs at 342nm. (1)H NMR and (13)C NMR
      spectroscopic studies were employed to elucidate the structure of the grown
      crystal. The second harmonic generation efficiency test by Kurtz-Perry technique
      showed positive result. The decomposition temperature of the grown crystal was
      studied by DTA/TGA analysis. The results observed from the characterization
      analyses show its suitability for NLO applications.

PMID- 22465774
TI  - Optimization for rapid synthesis of silver nanoparticles and its effect on
      phytopathogenic fungi.
AB  - In this present study, silver nanoparticles were synthesized by green chemistry
      approach using Acalypha indica leaf extract as reducing agents. The reaction
      medium employed in the synthesis process was optimized to attain better yield,
      controlled size and stability. Further, the biosynthesized silver nanoparticles
      were conformed through UV-vis spectrum, XRD and HR-TEM analyses. Different
      concentration of silver nanoparticles were tested to know the inhibitory effect
      of fungal plant pathogens namely Alternaria alternata, Sclerotinia sclerotiorum,
      Macrophomina phaseolina, Rhizoctonia solani, Botrytis cinerea and Curvularia
      lunata. Interestingly, 15 mg concentration of silver nanoparticles showed
      excellent inhibitory activity against all the tested pathogens. Thus, the
      obtained results clearly suggest that silver nanoparticles may have important
      applications in controlling various plant diseases caused by fungi.

PMID- 22465773
TI  - Synthesis, spectroscopic characterization and biological activities of N4O2
      Schiff base ligand and its metal complexes of Co(II), Ni(II), Cu(II) and Zn(II).
AB  - The Schiff base ligand, bis(indoline-2-one)triethylenetetramine (L) obtained from
      condensation of triethylenetetramine and isatin was used to synthesize the
      complexes of type, [ML]Cl(2) [M=Co(II), Ni(II), Cu(II) and Zn(II)]. L was
      characterized on the basis of the results of elemental analysis, FT-IR, (1)H and
      (13)C NMR, mass spectroscopic studies. The stoichiometry, bonding and
      stereochemistries of complexes were ascertained on the basis of results of
      elemental analysis, magnetic susceptibility values, molar conductance and various
      spectroscopic studies. EPR, UV-vis and magnetic moments revealed an octahedral
      geometry for complexes. L and its Cu(II) and Zn(II) complexes were screened for
      their antibacterial activity. Analgesic activity of Cu(II) and Zn(II) complexes
      was also tested in rats by tail flick method. Both complexes were found to
      possess good antibacterial and moderate analgesic activity.

PMID- 22465775
TI  - Enhanced photocatalytic activity of metal coated ZnO nanowires.
AB  - A simple, facile and template free route has been described for the synthesis of
      ZnO nanowires. The morphology and structure of ZnO nanowires have been tuned by
      deposing silver and gold onto the surface of ZnO nanowire and this has been done
      by adding AgNO(3) and HAuCl(4) to aqueous suspension of ZnO. Our synthesized Ag
      and Au coated ZnO nanoparticles show different emissive property than the native
      ZnO nanowires. The photocatalytic degradation of Methylene Blue is also evaluated
      using ZnO and Ag and Au coated ZnO nanowires. It has been observed that Ag coated
      ZnO nano-needles exhibits significantly enhanced photocatalytic efficiency
      compare to ZnO nanowire and Au coated ZnO nano-leaves. Fluorescence spectra and
      surface structure of the samples with their photocatalytic activity indicates
      that surface deposited metal serves as an electron sinks to enhance the
      separation of photoinduced electrons from holes, leading to the formation of OH
      and it enhances their photocatalytic efficiency.

PMID- 22465776
TI  - Crystal structure, spectroscopic investigations and density functional studies of
      4-(4-methoxyphenethyl)-5-benzyl-2H-1,2,4-triazol-3(4H)-one monohydrate.
AB  - The triazol compound 4-(4-methoxyphenethyl)-5-benzyl-2H-1,2,4-triazol-3(4H)-one
      monohydrate (I) has been synthesized and characterized by (1)H NMR, (13)C NMR,
      IR, and X-ray single-crystal determination. The molecular geometry, vibrational
      frequencies and gauge including atomic orbital (GIAO) (1)H and (13)C NMR chemical
      shift values of (I) in the ground state have been calculated using the density
      functional method (B3LYP) with the 6-31G(d) basis set. The calculated results
      show that the optimized geometry can well reproduce the crystal structure, and
      the theoretical vibrational frequencies and chemical shift values show good
      agreement with experimental values. The energetic behavior of (I) in solvent
      media was examined using the B3LYP method with the 6-31G(d) basis set by applying
      the Onsager and the polarizable continuum model (PCM). The predicted non-linear
      optical properties of (I) are greater than ones of urea. In addition, DFT
      calculations of molecular electrostatic potentials, frontier molecular orbitals
      and thermodynamic properties of (I) were carried out at the B3LYP/6-31G(d) level
      of theory.

PMID- 22465777
TI  - Thin film assembly of nano-sized Zn(II)-8-hydroxy-5,7-dinitroquinolate by using
      successive ion layer adsorption and reaction (SILAR) technique: characterization
      and optical-electrical-photovoltaic properties.
AB  - A method is described for thin film assembly of nano-sized Zn(II)-8-hydroxy-5,7
      dinitroquinolate complex, Zn[((NO(2))(2)-8HQ)(2)] by using successive ion layer
      adsorption and reaction (SILAR) technique. Highly homogeneous assembled nano
      sized metal complex thin films with particle size distribution in the range 27
      47nm was identified by using scanning electron microscopy (SEM). Zn[((NO(2))(2)
      8HQ)(2)] and [(NO(2))(2)-8HQ] ligand were studied by thermal gravimetric analysis
      (TGA). Graphical representation of temperature dependence of the dark electrical
      conductivity produced two distinct linear parts for two activation energies at
      0.377eV and 1.11eV. The analysis of the spectral behavior of the absorption
      coefficient in the intrinsic absorption region reveals a direct allowed
      transition with a fundamental band gap of 2.74eV. The dark current density
      voltage (J-V) characteristics showed the rectification effect due to the
      formation of junction barrier of Zn[((NO(2))(2)-8HQ)(2)] complex film/n-Si
      interface. The photocurrent in the reverse direction is strongly increased by
      photo-illumination and the photovoltaic characteristics were also determined and
      evaluated.

PMID- 22465778
TI  - Binding of dihydromyricetin to human hemoglobin: fluorescence and circular
      dichroism studies.
AB  - The binding reaction between dihydromyricetin (DMY) and human hemoglobin (HHb)
      was investigated systematically with various spectroscopic methods including
      fluorescence quenching technique, ultraviolet (UV)-vis absorption, synchronous
      fluorescence, circular dichroism (CD) spectroscopy. The experimental results
      showed that DMY effectively quenched the intrinsic fluorescence of HHb via static
      quenching. DMY binds to HHb with a stoichiometry that varies from 0.972:1 to
      0.906:1 as the temperature increases from 296 to 304 K. The DMY-HHb binding
      constants were determined to be K(296)=2.79 * 10(4) and K(304)=1.18 * 10(4) Lmol(
      1). The reaction is characterized by negative enthalpy (DeltaH=-80.46 kJ mol(-1))
      and negative entropy (DeltaS=-186.72 kJ mol(-1)), indicating that the predominant
      forces in the DMY-HHb complex are van der Waals and hydrogen bonding forces.
      Based on the Forster's theory of non-radiative energy transfer, the binding
      distance between DMY and the inner tryptophan residues of HHb was determined to
      be 3.15 nm. Furthermore, the CD spectroscopy indicated the secondary structure of
      HHb is not changed in the presence of DMY.

PMID- 22465779
TI  - Value of susceptibility-weighted imaging in acute hemorrhagic leukoencephalitis.
AB  - Acute hemorrhagic leukoencephalitis (AHL) is a rapidly progressive disease in the
      spectrum of acute disseminated encephalomyelitis. Timely accurate diagnosis is
      crucial but challenging clinically and radiologically. However, imaging findings
      of AHL are quite specific when susceptibility-weighted imaging is utilized. The
      purpose of this report is to present the imaging findings of autopsy-proven AHL
      and thus to facilitate rapid recognition and treatment.

PMID- 22465780
TI  - Nicotinamide treatment reduces the levels of histone H3K4 trimethylation in the
      promoter of the mper1 circadian clock gene and blocks the ability of
      dexamethasone to induce the acute response.
AB  - Circadian rhythms, which measure time on a scale of 24h, are generated by one of
      the most ubiquitous endogenous mechanisms, the circadian clock. SIRT1, a class
      III histone deacetylase, and PARP-1, a poly(ADP-ribose) polymerase, are two
      NAD(+)-dependent enzymes that have been shown to be involved in the regulation of
      the clock. Here we present evidence that the metabolite nicotinamide, an
      inhibitor of SIRT1, PARP-1 and mono(ADP-ribosyl) transferases, blocks the ability
      of dexamethasone to induce the acute response of the circadian clock gene, mper1,
      while it concomitantly reduces the levels of histone H3 trimethylation of lysine
      4 (H3K4me3) in the mper1 promoter. Moreover, application of alternative
      inhibitors of SIRT1 and ADP-ribosylation did not lead to similar results.
      Therefore, inhibition of these enzymes does not seem to be the mode by which NAM
      exerts these effects. These results suggest the presence of a novel mechanism,
      not previously documented, by which NAM can alter gene expression levels via
      changes in the histone H3K4 trimethylation state.

PMID- 22465781
TI  - Characterization of multiple membrane progestin receptor (mPR) subtypes from the
      goldfish ovary and their roles in the induction of oocyte maturation.
AB  - Oocyte maturation (OM) in goldfish is induced by the maturation inducing hormone
      (MIH) via its membrane receptor. Previously, we described the cloning of the
      membrane progesterone receptor alpha (mPRalpha or paqr7b) cDNA from a goldfish
      ovarian cDNA library and obtained experimental evidence that the mPRalpha protein
      is an intermediary in MIH induction of OM in goldfish. Three mPR subtypes have
      been identified in fish by cDNA cloning or by in silico analysis of genome
      sequence databases. In order to investigate the potential roles of the mPR
      subtypes in oocyte maturation, we cloned additional mPRs from a goldfish ovarian
      cDNA library. RACE amplification, and screening of the cDNA library identified
      one beta (paqr8) and two gamma subtypes (paqr5) (hereafter referred to as gamma-1
      and gamma-2), respectively. Tissue distribution of mPR subtypes showed
      differential expression pattern. However, in addition to mPRalpha, the beta,
      gamma-1 and gamma-2 subtypes were also expressed in follicle-enclosed oocytes.
      Cell lines expressing the beta, gamma-1 and gamma-2 genes were established and
      their steroid binding properties compared. The beta subtype exhibited higher
      binding affinity than the gamma subtypes for 17,20beta-DHP, the MIH in goldfish.
      Microinjection of goldfish oocytes with a morpholino antisense oligonucleotide to
      mPRbeta blocked the induction of oocyte maturational competence, whereas
      injection of antisense oliogonucleotides to mPRgamma-1 and gamma-2 were
      ineffective. These results suggest that the goldfish mPRbeta protein acts as an
      intermediary during MIH induction of OM in goldfish, in a manner similar to that
      described previously for mPRalpha.

PMID- 22465782
TI  - Effect of dehydroepiandrosterone on cell growth and mitochondrial function in TM
      3 cells.
AB  - Dehydroepiandrosterone (DHEA), a major steroid hormone, decreases with age, and
      this reduction has been shown to be associated with physical health. In the
      present study, the effect of DHEA on cell growth and mitochondrial function was
      investigated using TM-3 cells, a Leydig cell line. The growth of TM-3 cells
      exposed to 100 MUM DHEA for 24h was inhibited due to cell cycle arrest, primarily
      in the S and G2/M phases, and this effect was caused by decreased activity of
      glucose-6-phosphate dehydrogenase (G6PD) and reduced expression of cyclinA and
      cyclinB mRNA. A novel finding was that DHEA improved TM-3 cell viability in a
      markedly time-dependent manner. Although no differences were observed in the
      configuration or number of TM-3 cell mitochondria following DHEA treatment,
      mitochondrial membrane permeability and the activity of succinate dehydrogenase
      (SDH) increased subsequent to 24h treatment of cells with 100 MUM DHEA. Overall,
      the data demonstrate that DHEA inhibited TM-3 cell growth by decreasing G6PD
      activity and the expression of cyclin mRNAs, whereas it improved TM-3 cell
      viability by increasing mitochondrial membrane permeability and the activity of
      SDH. This could be one of mechanisms of DHEA exerts its biological function.

PMID- 22465784
TI  - Triazine dendrimers as drug delivery systems: from synthesis to therapy.
AB  - The use of triazine dendrimers as drug delivery systems benefits from their
      synthetic versatility and well-defined structure. Triazine dendrimers can be
      designed and readily synthesized to display orthogonally functional surfaces that
      facilitate post-synthetic manipulation such as attachment of drug, PEGylation,
      and/or the installation of ligands or reporting groups. The synthesis is
      scalable, and large generations can be accessed. To date, triazine dendrimers
      have been probed for a variety of medicinal applications including drug delivery
      with an emphasis on cancer, nonviral DNA and RNA delivery systems, in sensing
      applications, and as bioactive materials. Specifically, triazine adducts with
      paclitaxel, camptothecin, brefeldin A, and desferrioxamine have been prepared and
      assessed. Paclitaxel constructs show promising activity in vivo. The use of these
      materials in fluorescence-based glucose sensors is being pursued. Glycosylated
      triazine dendrimers interfere with signal transduction in the Toll-4 receptor
      pathway.

PMID- 22465783
TI  - Reservoir-based drug delivery systems utilizing microtechnology.
AB  - This review covers reservoir-based drug delivery systems that incorporate
      microtechnology, with an emphasis on oral, dermal, and implantable systems. Key
      features of each technology are highlighted such as working principles,
      fabrication methods, dimensional constraints, and performance criteria. Reservoir
      based systems include a subset of microfabricated drug delivery systems and
      provide unique advantages. Reservoirs, whether external to the body or implanted,
      provide a well-controlled environment for a drug formulation, allowing increased
      drug stability and prolonged delivery times. Reservoir systems have the
      flexibility to accommodate various delivery schemes, including zero order,
      pulsatile, and on demand dosing, as opposed to a standard sustained release
      profile. Furthermore, the development of reservoir-based systems for targeted
      delivery for difficult to treat applications (e.g., ocular) has resulted in
      potential platforms for patient therapy.

PMID- 22465785
TI  - Predictive combinations of monitor alarms preceding in-hospital code blue events.
AB  - Bedside monitors are ubiquitous in acute care units of modern healthcare
      enterprises. However, they have been criticized for generating an excessive
      number of false positive alarms causing alarm fatigue among care givers and
      potentially compromising patient safety. We hypothesize that combinations of
      regular monitor alarms denoted as SuperAlarm set may be more indicative of
      ongoing patient deteriorations and hence predictive of in-hospital code blue
      events. The present work develops and assesses an alarm mining approach based on
      finding frequent combinations of single alarms that are also specific to code
      blue events to compose a SuperAlarm set. We use 4-way analysis of variance
      (ANOVA) to investigate the influence of four algorithm parameters on the
      performance of the data mining approach. The results are obtained from millions
      of monitor alarms from a cohort of 223 adult code blue and 1768 control patients
      using a multiple 10-fold cross-validation experiment setup. Using the optimal
      setting of parameters determined in the cross-validation experiment, final
      SuperAlarm sets are mined from the training data and used on an independent test
      data set to simulate running a SuperAlarm set against live regular monitor
      alarms. The ANOVA shows that the content of a SuperAlarm set is influenced by a
      subset of key algorithm parameters. Simulation of the extracted SuperAlarm set
      shows that it can predict code blue events one hour ahead with sensitivity
      between 66.7% and 90.9% while producing false SuperAlarms for control patients
      that account for between 2.2% and 11.2% of regular monitor alarms depending on
      user-supplied acceptable false positive rate. We conclude that even though the
      present work is still preliminary due to the usage of a moderately-sized database
      to test our hypothesis it represents an effort to develop algorithms to alleviate
      the alarm fatigue issue in a unique way.

PMID- 22465786
TI  - Semantic mapping to simplify deployment of HL7 v3 Clinical Document Architecture.
AB  - HL7 Version 3 was developed to provide semantically reliable healthcare
      interoperability but has been perceived as overly complex to implement. This
      paper describes how semantic mapping can simplify usage of HL7 Version 3 Clinical
      Document Architecture (CDA) and reports on the rationale for adopting this
      approach in three particular use cases and lessons learned from the practical
      application experience. We envision a broad application of the semantic mapping
      approach in clinical documents, messaging and application design modelling.

PMID- 22465787
TI  - Histological classification of malignant renal tumours at a time of major
      diagnostic and therapeutic changes.
AB  - Renal cancers account for approximately 3% of adult cancers and the mean age of
      diagnosis is 65, with men affected two to three times more frequently than women.
      However, an increase is being seen in kidney tumours also in young adults and in
      women. The classification of renal tumours includes both benign and malignant
      tumours, and is currently quite exhaustive, but may be even more extensive in the
      coming years, particularly for tumours in renal impairment. Except for certain
      specific entities (such as chromophobe carcinoma), two criteria are required to
      correctly classify malignant kidney tumours: the Fuhrman grade, and the pTNM
      stage, defining tumour extension. The stage and grade are applicable in the same
      way, regardless of the nature of the tumours; for a given group, they are the
      best prognostic factors.

PMID- 22465788
TI  - Detecting prostate cancer with MRI - why and how.
AB  - Multiparametric MRI of the prostate is an essential examination for the
      diagnosis, preoperative evaluation and planning of treatment for prostate cancer.
      This examination can accurately detect cancer foci in the gland so that the most
      appropriate management can be offered, reduce the risk of over-treatment and also
      ensure that certain aggressive lesions or unusual locations, which might affect
      the prognosis, are not ignored. We present here its main indications, focusing on
      the techniques for interpreting MRI, its performance and its limitations, as well
      as the recent European recommendations underlining the need for international
      harmonisation.

PMID- 22465789
TI  - MRI in addition to or as a substitute for prostate biopsy: the clinician's point
      of view.
AB  - This paper aims to argue the advantages of using routine multiparametric MRI (mp
      MRI) prior to the first series of biopsies in patients with suspected cancer of
      the prostate indicated by a rise in Prostatic Specific Antigen (PSA). Using
      biopsy targeted onto a lesion seen by MRI, this diagnostic strategy could
      increase detection of significant cancers and improve evaluation of their grade
      and size. This strategy would also mean that the detection of insignificant
      cancers (microfoci detected by chance during systematic biopsy) would decrease,
      since if the mp-MRI did not give rise to suspicion, the indications for biopsy
      would be reduced. It could also reduce the number of biopsies to be performed
      even when the mp-MRI is suspicious, by resorting solely to targeted biopsies.
      This review does not evaluate the role of mp-MRI in locoregional staging.

PMID- 22465790
TI  - The gradient index lens of the eye: an opto-biological synchrony.
AB  - The refractive power of a lens is determined largely by its surface curvatures
      and the refractive index of its medium. These properties can also be used to
      control the sharpness of focus and hence the image quality. One of the most
      effective ways of doing this is with a gradient index. Eye lenses of all species,
      thus far, measured, are gradient index (GRIN) structures. The index gradation is
      one that increases from the periphery of the lens to its centre but the steepness
      of the gradient and the magnitudes of the refractive index vary so that the
      optics of the lens accords with visual demands. The structural proteins, the
      crystallins, which create the index gradient, also vary from species to species,
      in type and relative distribution across the tissue. The crystallin classes do
      not contribute equally to the refractive index, and this may be related to their
      structure and amino acid content. This article compares GRIN forms in eye lenses
      of varying species, the relevance of these forms to visual requirements, and the
      relationship between refractive index and the structural proteins. Consideration
      is given to the dynamics of a living lens, potential variations in the GRIN form
      with physiological changes and the possible link between discontinuities in the
      gradient and growth. Finally, the property of birefringence and the
      characteristic polarisation patterns seen in highly ordered crystals that have
      also been observed in specially prepared eye lenses are described and discussed.

PMID- 22465791
TI  - Lutein: more than just a filter for blue light.
AB  - Lutein is concentrated in the primate retina, where together with zeaxanthin it
      forms the macular pigment. Traditionally lutein is characterized by its blue
      light filtering and anti-oxidant properties. Eliminating lutein from the diet of
      experimental animals results in early degenerative signs in the retina while
      patients with an acquired condition of macular pigment loss (Macular
      Telangiectasia) show serious visual handicap indicating the importance of macular
      pigment. Whether lutein intake reduces the risk of age related macular
      degeneration (AMD) or cataract formation is currently a strong matter of debate
      and abundant research is carried out to unravel the biological properties of the
      lutein molecule. SR-B1 has recently been identified as a lutein binding protein
      in the retina and this same receptor plays a role in the selective uptake in the
      gut. In the blood lutein is transported via high-density lipoproteins (HDL).
      Genes controlling SR-B1 and HDL levels predispose to AMD which supports the
      involvement of cholesterol/lutein transport pathways. Apart from beneficial
      effects of lutein intake on various visual function tests, recent findings show
      that lutein can affect immune responses and inflammation. Lutein diminishes the
      expression of various ocular inflammation models including endotoxin induced
      uveitis, laser induced choroidal neovascularization, streptozotocin induced
      diabetes and experimental retinal ischemia and reperfusion. In vitro studies show
      that lutein suppresses NF kappa-B activation as well as the expression of iNOS
      and COX-2. Since AMD has features of a chronic low-grade systemic inflammatory
      response, attention to the exact role of lutein in this disease has shifted from
      a local effect in the eye towards a possible systemic anti-inflammatory function.

PMID- 22465793
TI  - Development of electrochemiluminescence-based singleplex and multiplex assays for
      the quantification of alpha-synuclein and other proteins in cerebrospinal fluid.
AB  - The need for improved diagnostic accuracy and markers of progression in
      neurodegenerative diseases motivates the identification of objective biomarkers
      as well as optimized assays for their quantification. Several potential marker
      candidates for Parkinson's disease (PD) in cerebrospinal fluid have been
      identified. These include alpha-synuclein, a major constituent of the
      intracellular aggregates. We give a general overview and details of our
      experience in converting established enzyme-linked immunoabsorbent assays (for
      alpha-synuclein and other proteins) onto an electrochemiluminescence-based
      platform as well as considerations on multiplexing different assays for PD.

PMID- 22465792
TI  - Transcription activation by Escherichia coli Rob at class II promoters: protein
      protein interactions between Rob's N-terminal domain and the sigma(70) subunit of
      RNA polymerase.
AB  - Bacterial transcription activators regulate transcription by making essential
      protein-protein interactions with RNA polymerase, for example, with region 4 of
      the sigma(70) subunit (sigma(70) R4). Rob, SoxS, and MarA comprise a closely
      related subset of members of the AraC/XylS family of transcription factors that
      activate transcription of both class I and class II promoters. Recently, we
      showed that interactions between SoxS and sigma(70) R4 occlude the binding of
      sigma(70) R4 to the -35 promoter element of class II promoters. Although Rob
      shares many similarities with SoxS, it contains a C-terminal domain (CTD) that
      the other paralogs do not. Thus, a goal of this study was to determine whether
      Rob makes protein-protein interactions with sigma(70) R4 at class II promoters
      and, if so, whether the interactions occlude the binding of sigma(70) R4 to the 
      35 hexamer despite the presence of the CTD. We found that although Rob makes
      fewer interactions with sigma(70) R4 than SoxS, the two proteins make the same,
      unusual, position-dependent interactions. Importantly, we found that Rob occludes
      sigma(70) R4 from binding the -35 hexamer, just as does SoxS. Thus, the CTD does
      not substantially alter the way Rob interacts with sigma(70) R4 at class II
      promoters. Moreover, in contrast to inferences drawn from the co-crystal
      structure of Rob bound to robbox DNA, which showed that only one of Rob's dual
      helix-turn-helix (HTH) DNA binding motifs binds a recognition element of the
      promoter's robbox, we determined that the two HTH motifs each bind a recognition
      element in vivo.

PMID- 22465794
TI  - Protein selection using yeast surface display.
AB  - Binding proteins are typically isolated from combinatorial libraries of scaffold
      proteins using one of the many library screening tools available, such as phage
      display, yeast surface display or mRNA display. A key principle underlying these
      screening technologies is the establishment of a link between each unique mutant
      protein and its corresponding genetic code. The mutant proteins binding a desired
      target species are separated and subsequently identified using the genetic code.
      In this review, we largely focus on the use of yeast surface display for the
      isolation of binding proteins from combinatorial libraries. In yeast surface
      display, the yeast cell links the mutant protein to its coding DNA. Each yeast
      cell expresses the mutant proteins as fusions to a yeast cell wall protein; the
      yeast cell also carries plasmid DNA that codes for the mutant protein. Over the
      years, the yeast surface display platform has emerged as a powerful tool for
      protein engineering, and has been used in a variety of applications including
      affinity maturation, epitope mapping and biophysical characterization of
      proteins. Here we present a broad overview of the yeast surface display system
      and its applications, and compare it with other contemporary screening platforms.
      Further, we present detailed protocols for the use of yeast surface display to
      isolate de novo binding proteins from combinatorial libraries, and subsequent
      biophysical characterization of binders. These protocols can also be easily
      modified for affinity maturation of the isolated de novo binders.

PMID- 22465796
TI  - Quantitative proteomic analysis of yeast DNA replication proteins.
AB  - Chromatin is dynamically regulated, and proteomic analysis of its composition can
      provide important information about chromatin functional components. Many DNA
      replication proteins for example bind chromatin at specific times during the cell
      cycle. Proteomic investigation can also be used to characterize changes in
      chromatin composition in response to perturbations such as DNA damage, while
      useful information is obtained by testing the effects on chromatin composition of
      mutations in chromosome stability pathways. We have successfully used the method
      of stable isotope labeling by amino acids in cell culture (SILAC) for
      quantitative proteomic analysis of normal and pathological changes to yeast
      chromatin. Here we describe this proteomic method for analyzing changes to
      Saccharomyces cerevisiae chromatin, illustrating the procedure with an analysis
      of the changes that occur in chromatin composition as cells progress from a G1
      phase block (induced by alpha factor) into S phase (in the presence of DNA
      replication inhibitor hydroxyurea).

PMID- 22465795
TI  - Directed evolution as a powerful synthetic biology tool.
AB  - At the heart of synthetic biology lies the goal of rationally engineering a
      complete biological system to achieve a specific objective, such as
      bioremediation and synthesis of a valuable drug, chemical, or biofuel molecule.
      However, the inherent complexity of natural biological systems has heretofore
      precluded generalized application of this approach. Directed evolution, a process
      which mimics Darwinian selection on a laboratory scale, has allowed significant
      strides to be made in the field of synthetic biology by allowing rapid
      identification of desired properties from large libraries of variants.
      Improvement in biocatalyst activity and stability, engineering of biosynthetic
      pathways, tuning of functional regulatory systems and logic circuits, and
      development of desired complex phenotypes in industrial host organisms have all
      been achieved by way of directed evolution. Here, we review recent contributions
      of directed evolution to synthetic biology at the protein, pathway, network, and
      whole cell levels.

PMID- 22465797
TI  - Patterns and correlates of grip strength change with age in Afro-Caribbean men.
AB  - BACKGROUND: muscle strength is essential for physical functions and an indicator
      of morbidity and mortality in older adults. Among the factors associated with
      muscle strength loss with age, ethnicity has been shown to play an important
      role. OBJECTIVE: to examine the patterns and correlates of muscle strength change
      with age in a population-based cohort of middle-aged and older Afro-Caribbean
      men. METHODS: handgrip strength and body composition were measured in 1,710 Afro
      Caribbean men. Data were also collected for demographic variables, medical
      history and lifestyle behaviours. RESULTS: the age range of the study population
      was 29-89 years. Grip strength increased below age 50 years, and decreased after
      age 50 years over 4.5-year follow-up. The average loss in grip strength was 2.2%
      (0.49% per year) for ages 50 years or older and 3.8% (0.64% per year) for ages 65
      years or older. The significant independent predictors of grip strength loss
      included older age, a greater body mass index, lower initial arm lean mass and
      greater loss of arm lean mass. CONCLUSION: Afro-Caribbean men experience a
      significant decline in muscle strength with advanced age. The major independent
      factors associated with strength loss were similar to other ethnic groups,
      including age, body weight and lean mass.

PMID- 22465798
TI  - Outbreak of reproductive disorders and mycobacteriosis in swine associated with a
      single strain of Mycobacterium avium subspecies hominissuis.
AB  - In a breeding and fattening pig farm an increasing number of cases of abortion
      and generalized mycobacteriosis at slaughter occurred. Pathological findings
      compatible with mycobacteriosis, acid-fast organisms in tissues, and isolation of
      mycobacteria from tissue samples including fetuses, lungs and reproductive organs
      from sows, genital swabs, mesenteric lymph nodes, and from a sperm sample
      revealed the cause of the disease. Bacterial cultures were identified as
      Mycobacterium avium subsp. hominissuis using IS901-/IS1245-specific PCR.
      Genotyping of selected isolates from animals as well as from their environment by
      MIRU-VNTR analysis showed that the herd was infected with one single outbreak
      strain. The same genotype was also isolated from pigs of two other farms which
      showed comparable symptoms and were in direct contact with the index farm as well
      as from their environment. Immunological host responses detected by tuberculin
      skin test and ELISA gave positive results at herd level only. Despite the
      detection of other potential pathogens mycobacteria were regarded as the
      causative agent of the reproductive disorders. To our knowledge this is the first
      report of an epidemic mycobacterial infection in a pig holding associated with
      reproductive disorders, which could be attributed to one single virulent strain,
      and the first report of detection of M. avium subsp. hominissuis in pig sperm.

PMID- 22465799
TI  - The impact of quorum sensing on the virulence of Aeromonas hydrophila and
      Aeromonas salmonicida towards burbot (Lota lota L.) larvae.
AB  - In this study, the link between quorum sensing in Aeromonas spp. and its
      virulence towards burbot (Lota lota) was investigated. High mortality occurred in
      burbot juveniles challenged with Aeromonas salmonicida HN-00, but not in
      juveniles challenged with Aeromonas hydrophila AH-1N. Meanwhile, both A.
      hydrophila AH-1N and A. salmonicida HN-00 were virulent towards larvae. The
      effect of quorum sensing on the virulence of A. hydrophila AH-1N towards burbot
      larvae was further investigated using quorum sensing mutants (N-(butyryl)-L
      homoserine lactone production and receptor mutants). Challenge with these mutants
      resulted in higher survival of burbot larvae when compared to challenge with the
      wild type, and the addition of the signal molecule N-butyryl-L-homoserine lactone
      restored the virulence of the quorum sensing production mutant. Moreover, quorum
      sensing inhibitors protected the burbot larvae from both Aeromonas strains.
      Finally, the freshwater micro-algae Chlorella saccharophila and Chlamydomonas
      reinhardtii, which are able to interfere with quorum sensing, also protected
      burbot from the pathogens. However, QS interference was unlikely to be the only
      mechanism. This study revealed that the virulence of Aeromonas spp. towards
      burbot is regulated by quorum sensing and that quorum sensing inhibitors and
      micro-algae are promising biocontrol agents.

PMID- 22465800
TI  - Tissue localisation of Mycobacterium avium subspecies paratuberculosis following
      artificially induced intracellular and naked bacteraemia.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of
      Johne's disease or paratuberculosis, a chronic enteritis of ruminants. While
      Johne's disease is primarily expressed in the gastrointestinal tract, isolation
      of MAP from extra-intestinal tissues indicates that microbial dissemination via
      the haematogenous route may occur during the infection. This study examined the
      movement of peripheral blood mononuclear cells (PBMCs) infected with MAP and the
      dissemination of MAP following mycobacteraemia induced by IV inoculation over a
      time frame of 3 days. Viable MAP were detected in the peripheral blood by culture
      at 24, 48 and 72 h post IV inoculation in 3 of 4 sheep while a fourth sheep was
      blood culture positive at 24 and 48 h. Seventy-two hours following IV
      inoculation, MAP in tissues was unevenly distributed. MAP was predominantly
      distributed to the filtering organs, i.e. the lung, liver and spleen, however MAP
      was also isolated from lymph nodes, especially those draining the neck. MAP was
      not isolated from gastrointestinal tissues or lymph nodes, heart or kidney at 72
      h following IV inoculation. The rapidity of localisation of MAP to tissues after
      onset of induced bacteraemia suggests that intermittent seeding into blood in
      natural infection would be sufficient to account for dissemination.

PMID- 22465801
TI  - Pathogenicity characterization of a bovine triple reassortant rotavirus in calves
      and piglets.
AB  - Rotaviruses are important human and animal pathogens with high impact on public
      health and livestock industry. There is little evidence about the cross-species
      pathogenicity and extra-intestinal infections of animal and human reassortant
      rotaviruses, particularly based on all 11 genotyping data. In this study, the
      bovine triple reassortant KJ56-1 strain harboring two bovine-like genome
      segments, eight porcine-like genome segments, and one human-like genome segment
      was used to evaluate the cross-species pathogenicity in its parent species,
      calves and piglets, and to determine its abilities of causing viremia and extra
      intestinal tropisms in piglets. The KJ56-1 strain isolated from a calf diarrhea
      fecal sample replicated without causing diarrhea and severe intestinal pathology
      in calves. However, piglets inoculated with this strain showed persistent severe
      diarrhea and marked intestinal pathology. By SYBR Green real-time RT-PCR, viral
      RNA was detected in the sera, mesenteric lymph node, lung, liver, choroid plexus,
      and cerebrospinal fluid in the experimental piglets. An immunofluorescence assay
      confirmed viral replication in these extra-intestinal organs and tissues. These
      results indicated that the bovine triple reassortant KJ56-1 strain was virulent
      to piglets but not to calves. Our data also demonstrated that the reassortant
      rotaviruses had the ability to spread to the bloodstream from the gut, enter and
      amplify in the mesenteric lymph node, and disseminate to the extra-intestinal
      organs and tissues.

PMID- 22465803
TI  - High-fructose corn syrup causes vascular dysfunction associated with metabolic
      disturbance in rats: protective effect of resveratrol.
AB  - High-fructose corn syrup (HFCS) is used in many prepared foods and soft drinks.
      However, limited data is available on the consequences of HFCS consumption on
      metabolic and cardiovascular functions. This study was, therefore, designed to
      assess whether HFCS drinking influences the endothelial and vascular function in
      association with metabolic disturbances in rats. Additionally, resveratrol was
      tested at challenge with HFCS. We investigated the effects of HFCS (10% and 20%)
      and resveratrol (50mg/l) beverages on several metabolic parameters as well as
      endothelial relaxation, vascular contractions, expressions of endothelial nitric
      oxide synthase (eNOS), sirtuin 1 (SIRT1), gp91(phox) and p22(phox) proteins and
      superoxide generation in the aortas. Consumption of HFCS (20%) increased serum
      triglyceride, VLDL and insulin levels as well as blood pressure. Impaired
      relaxation to acetylcholine and intensified contractions to phenylephrine and
      angiotensin II were associated with decreased eNOS and SIRT1 whereas increased
      gp91(phox) and p22(phox) proteins, along with provoked superoxide production in
      the aortas from HFCS-treated rats. Resveratrol supplementation efficiently
      restored HFCS-induced deteriorations. Thus, intake of HFCS leads to vascular
      dysfunction by decreasing vasoprotective factors and provoking oxidative stress
      in association with metabolic disturbances. Resveratrol has a protective
      potential against the harmful consequences of HFCS consumption.

PMID- 22465802
TI  - A simplified PCR method for genotyping Mycoplasma mycoides subspecies mycoides
      small colony: the aetiologic agent of contagious bovine pleuropneumonia.
AB  - Mycoplasma mycoides subspecies mycoides small colony is the aetiological agent of
      contagious bovine pleuropneumonia, a cattle disease endemic to areas of sub
      Saharan Africa. Twenty isolates from various geographical locations and the type
      strain were analysed by multi-locus sequence analysis (MLSA). The data generated
      was then used to develop three PCR primer sets to differentiate these isolates.
      The PCRs differentiated the isolates into four groups; the type strain (T);
      isolates of European origin (Eu); isolates from Tanzania (Af1) with a final group
      consisting of isolates from Namibia and Botswana (Af2). These PCRs offers a rapid
      and efficient post-identification typing method without the need to sequence and
      analyse multiple genes.

PMID- 22465804
TI  - Eriodictyol-7-O-glucoside, a novel Nrf2 activator, confers protection against
      cisplatin-induced toxicity.
AB  - Eriodictyol-7-O-glucoside, a flavonoid isolated from Dracocephalum rupestre, is
      among the most potent free radical scavenger. In the present study, we identified
      eriodictyol-7-O-glucoside as a novel nuclear factor E2-related factor 2 (Nrf2)
      activator using a high-throughput cellular screening method. This compound
      activated Nrf2 signaling pathway and was able to stabilize Nrf2 by delaying Nrf2
      degradation, resulting in accumulation of Nrf2 protein and activation of the Nrf2
      dependent protective response. Recent studies have suggested that activation of
      Nrf2 pathway would confer protection against cisplatin-induced toxicity. The
      protective role of eriodictyol-7-O-glucoside in cisplatin-induced toxicity was
      investigated in a human renal mesangial cell line, HRMC. Cotreatment of HRMC
      cells with eriodictyol-7-O-glucoside significantly improved cell survival under
      cisplatin exposure. These findings demonstrated the feasibility of using natural
      compounds targeting Nrf2 as a therapeutic approach to subvert the side effects of
      cisplatin in normal cells.

PMID- 22465805
TI  - Power-efficient simulation of detailed cortical microcircuits on SpiNNaker.
AB  - Computer simulation of neural matter is a promising methodology for understanding
      the function of the brain. Recent anatomical studies have mapped the intricate
      structure of cortex, and these data have been exploited in numerous simulations
      attempting to explain its function. However, the largest of these models run
      inconveniently slowly and require vast amounts of electrical power, which hinders
      useful experimentation. SpiNNaker is a novel computer architecture designed to
      address these problems using low-power microprocessors and custom communication
      hardware. We use four SpiNNaker chips (of a planned fifty thousand) to simulate,
      in real-time, a cortical circuit of ten thousand spiking neurons and four million
      synapses. In this simulation, the hardware consumes 100 nJ per neuron per
      millisecond and 43 nJ per postsynaptic potential, which is the smallest quantity
      reported for any digital computer. We argue that this approaches fast, power
      feasible and scientifically useful simulations of large cortical areas.

PMID- 22465806
TI  - Coenzyme Q10 levels are low and associated with increased mortality in post
      cardiac arrest patients.
AB  - AIM: Survival after cardiac arrest (CA) is limited by the profound neurologic
      insult from ischemia-reperfusion injury. Therapeutic options are limited.
      Previous data suggest a benefit of coenzyme Q(10) (CoQ(10)) in post-arrest
      patients. We hypothesized that plasma CoQ(10) levels would be low after CA and
      associated with poorer outcomes. METHODS: Prospective observational study of post
      arrest patients presenting to a tertiary care center. CoQ(10) levels were drawn
      24h after return of spontaneous circulation (ROSC) and compared to healthy
      controls. Levels of inflammatory cytokines and biomarkers were analyzed. Primary
      endpoints were survival to discharge and neurologic status at time of discharge.
      RESULTS: 23 CA subjects and 16 healthy controls were enrolled. CoQ(10) levels in
      CA patients (0.28 MUmol L(-1), inter-quartile range (IQR): 0.22-0.39) were
      significantly lower than in controls (0.75 MUmol L(-1), IQR: 0.61-1.08,
      p<0.0001). The mean CoQ(10) level in CA patients who died was significantly lower
      than in those who survived (0.27 vs 0.47 MUmol L(-1), p = 0.007). There was a
      significant difference in median CoQ(10) level between patients with a good vs
      poor neurological outcome (0.49 MUmol L(-1), IQR: 0.30-0.67 vs 0.27 MUmol L(-1),
      IQR: 0.21-0.30, p = 0.02). CoQ(10) was a statistically significant predictor of
      poor neurologic outcome (adjusted p = 0.02) and in-hospital mortality (adjusted p
      = 0.026). CONCLUSION: CoQ(10) levels are low in human subjects with ROSC after
      cardiac arrest as compared to healthy controls. CoQ(10) levels were lower in
      those who died, as well as in those with a poor neurologic outcome.

PMID- 22465807
TI  - Impairment of carotid artery blood flow by supraglottic airway use in a swine
      model of cardiac arrest.
AB  - OBJECTIVE: Supraglottic airway devices (SGDs) are often used as an alternative to
      endotracheal tube (ETT) during cardiopulmonary resuscitation (CPR). SGDs can be
      inserted 'blindly' and rapidly, without stopping compressions. These devices
      utilize pressurized balloons to direct air to the trachea and prevent esophagus
      insufflation. We hypothesize that the use of a SGD will compress the carotid
      artery and decrease carotid blood flow (CBF) during CPR in pigs. METHODS:
      Ventricular fibrillation (VF) was induced in 9 female pigs (32 +/- 1 kg) followed
      by 4 min without compressions. CPR was then performed continuously for 3-6-min
      intervals. During each interval, an ETT was used for the first 3 min, followed by
      3 min of each SGD (King LTS-DTM, LMA FlexibleTM, CombitubeTM) in a random order.
      The primary endpoint was mean CBF (ml/min). Statistical comparisons among the 4
      airway devices were performed by Wilcoxon Rank test. Post mortem carotid
      arteriographies were performed with SGDs in place. RESULTS: CBF (median ml/min;
      25/75 percentile) was significantly lower with each SGD [King (10; 6/41), LMA
      (10; 4/39), and Combitube (5; -0.4/15)] versus ETT (21; 14/46) (p<0.05 for each
      SGD compared with ETT). Arteriograms showed that with each SGD there was
      compression of the internal and external carotid vessels. CONCLUSION: The use of
      3 different SGDs during CPR significantly decreased CBF in a porcine model of
      cardiac arrest. While the current study is limited to pigs, the findings suggest
      that further research on the effects of SGD use in humans and the effects on
      carotid artery blood flow is warranted.

PMID- 22465808
TI  - PlexinA4 distribution in the adult rat spinal cord and dorsal root ganglia.
AB  - PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to
      neuropilin 1 and 2, PlexinA4 being the latest member of the PlexinA subfamily to
      be identified. Little is known about the cellular distribution of PlexinA4 in the
      spinal cord and dorsal root ganglion (DRG). Here, immunohistochemical studies
      using antibodies to PlexinA4 revealed immunolabeling in neurons in both dorsal
      and, to a greater extent, ventral horns of the spinal cord. Ventral horn PlexinA4
      positive neurons exhibited morphology, size, and location consistent with both
      motor neurons and interneurons. Labeling was found in motor axons exiting through
      the ventral roots, and more widespread labeling was observed in ascending and
      descending white matter tracts. Within the DRG, immunostaining was observed in
      neuronal cell bodies as well as the central and peripheral processes of these
      cells. PlexinA4 is expressed in the peripheral nervous system where its
      expression is regulated upon nerve injury. This is the first detailed description
      of the cellular and subcellular distribution of PlexinA4 in the adult spinal cord
      and DRG, and it will set the basis for future studies on the potential role of
      PlexinA4 in regeneration and repair of the adult central and peripheral nervous
      system.

PMID- 22465810
TI  - Expression of concern re: Kulminski, A. 2011. Complex phenotypes and phenomenon
      of genome-wide inter-chromosomal linkage disequilibrium in the human genome.
      Experimental Gerontology. DOI: 10.1016/j.exger.2011.08.010.

PMID- 22465809
TI  - G-protein-gated inwardly rectifying K+ channel 4 (GIRK4) immunoreactivity in
      chemically defined neurons of the hypothalamic arcuate nucleus that control body
      weight.
AB  - G-protein-gated inwardly rectifying K(+) channels (GIRKs; also called Kir3) are a
      family of K(+) channels, which are activated (opened) via a signal transduction
      cascade starting with ligand-stimulated G-protein-coupled receptors (GPCRs). Four
      GIRK genes have been identified (GIRK1-4). GIRK4 (Kir3.4) has a role in
      regulating energy homeostasis, since mice with a targeted mutation in the GIRK4
      gene exhibit a predisposition to late-onset obesity. GIRK4 mRNA is expressed in
      hypothalamic regions that harbor neurons involved in the regulation of food
      intake and body weight. Using goat and rabbit antisera to the GIRK4 protein, the
      cellular localization and transmitter content of GIRK4-immunoreactive neurons was
      determined in the hypothalamic arcuate nucleus, a region that contains neurons
      which are accessible to circulating hormones and is intimately associated with
      the control of body weight. GIRK4-immunoreactive large cell bodies were
      demonstrated in the ventrolateral part of the arcuate nucleus, with smaller
      neuronal cell bodies in the ventromedial part of the nucleus. Double-labeling
      showed presence of GIRK4 immunoreactivity in large neurons of the ventrolateral
      arcuate nucleus containing the peptides alpha-melanocyte-stimulating hormone
      (alpha-MSH), a marker for pro-opiomelanocortin (POMC) neurons, and cocaine- and
      amphetamine-regulated transcript (CART). GIRK4 immunoreactivity was also seen in
      neurons of the ventromedial part of the arcuate nucleus containing agouti
      regulated peptide (AgRP) and neuropeptide Y (NPY). The results suggest that the
      GIRK4 channel protein plays a role in regulating membrane excitability in
      chemically defined neurons of the arcuate nucleus that control body weight.

PMID- 22465812
TI  - Reversal of slow growth and heartbeat through the restoration of mitochondrial
      function in clk-1-deficient mouse embryos by exogenous administration of coenzyme
      Q10.
AB  - The longevity gene clk-1/coq7 encodes an enzyme that is essential for the
      biosynthesis of coenzyme Q (CoQ) in mitochondria and regulates the lifespan and
      behavioral timing in Caenorhabditis elegans and the chronological lifespan in
      fission yeast. However, whether the mammalian clk-1/coq7 ortholog (clk-1)
      regulates these phenotypes in mammals remains to be fully evaluated due to the
      embryonic lethality of clk-1-deficient (clk-1(-/-)) mice. To investigate whether
      clk-1 regulates biological functions, such as growth and heartbeat, through CoQ
      in mouse embryos, we cultivated the cells and hearts of clk-1(-/-) mouse embryos
      at embryonic day 10.5 (E10.5) for at least 10 days in the presence of fetal
      bovine serum. In embryonic cells, cardiomyocytes, and hearts, the growth and
      heart rates were significantly slowed in clk-1(-/-) compared with wild-type or
      heterozygous mouse tissues. Moreover, frequent apoptosis and a significant
      reduction in mitochondrial functions, including membrane potential and ATP
      production, were observed in the clk-1(-/-) cells and hearts. The slowed growth
      and heart rates and the reduced mitochondrial function of clk-1(-/-) embryonic
      cells and hearts in culture were almost completely rescued by the administration
      of exogenous CoQ(10). The results indicate that clk-1 regulates growth and heart
      rates through CoQ-mediated mitochondrial functions in mouse embryos.

PMID- 22465813
TI  - Blood flow resistance in lesion vessels and normal host vessels evaluated by
      pulsed Doppler ultrasound.
AB  - Blood flow rate in the microcirculation is proportional to the arteriole-venule
      pressure difference and inversely proportional to the blood flow resistance
      (BFR). Generally, the BFR studies to date have focused on using invasive methods
      and were carried out in non-physiological conditions. Moreover, few studies have
      been concerned with the relationships of BFR between the tumor vessels and the
      normal host vessels. The present study investigated the BFR in malignant lesion
      vessels, benign lesion vessels and normal host vessels in physiological
      conditions using pulsed Doppler ultrasound as a tool and the thyroid as a model,
      A total of 133 patients with thyroid nodules were included in the study. The
      results revealed that most of the BFR parameters were higher in malignant lesion
      vessels than in benign lesion vessels (P=0.001-0.029), as well as lower in normal
      host vessels than in malignant or benign lesion vessels (P=0.000-0.017); Low to
      moderate significant positive correlations of BFR between benign lesion vessels
      and normal host vessels were also found (r=0.358-0.480, P=0.000 for all). Finally
      and interestingly, low negative correlations between the malignant nodule sizes
      and some of the BFR parameters were revealed, though these correlations were not
      statistically significant (r=-0.205--0.261, P=0.108-0.211). Our results suggested
      that pulsed Doppler ultrasound could be successfully used to measure BFR in
      physiological conditions and to reveal the BFR relationship between lesion
      vessels and normal host vessels, as well as the relationship between the lesion
      sizes and the BFR.

PMID- 22465814
TI  - Effects of temperature and photoperiod on postponing bermudagrass (Cynodon
      dactylon [L.] Pers.) turf dormancy.
AB  - Growth chamber and field experiments were carried out to determine the effects of
      extended photoperiod under low and freezing temperatures on bermudagrass turf
      dormancy at Bajgah, in the southern part of Iran. The experiment in the growth
      chamber was conducted with four temperature regimes (15, 7.5, 0 and -7.5 degrees
      C) and three light durations (8, 12 and 16h) in a completely randomized design
      with four replications. The field study was conducted in two consecutive years
      (2008-2009) with three light durations (8, 12 and 16h) in months with natural
      short day length and arranged in a randomized complete blocks design with three
      replications. Results in both experiments showed that decreasing temperature and
      photoperiod decreased verdure fresh and dry weight, shoot height, tiller density,
      leaf area and chlorophyll and relative water contents (RWC). However, rooting
      depth and fresh weight of roots increased in the growth chamber. Decreasing the
      temperature and light duration increased electrolyte leakage and proline content.
      Reducing sugars increased with decreasing temperature and declined with lowering
      light duration in both shoots and roots. Starch content of both shoots and roots
      showed an adverse trend compared to reducing sugars; starch content increased in
      both shoots and roots in all treatments by shortening the photoperiod.
      Practically, the problem of bermudagrass turf's dormancy could be solved via
      increasing the photoperiod in months with short day lengths. This treatment would
      be efficient and useful for turfgrass managers to apply in landscapes and
      stadiums.

PMID- 22465815
TI  - Combination of group I mGlu receptors antagonist with dopaminergic agonists
      strengthens the synaptic transmission at corticostriatal synapses in culture.
AB  - Restoring synaptic plasticity in neurodegenerative diseases could prevent
      neuronal degeneration, as well as motor and cognitive disorders. In Parkinson's
      disease, synaptic plasticity at corticostriatal synapses is altered. Dendrites of
      striatal medium spiny neurons (MSNs) receive dopaminergic inputs from the
      substantia nigra and glutamatergic cortical afferents. Because both glutamate and
      dopamine are required to induce and sustain MSNs plasticity, the particular
      molecular mechanisms involved at this synaptic triad are difficult to understand.
      In the present work, we established a convenient in vitro model of the
      corticostriatal synapse to study synaptic plasticity. We focused on long-term
      depression involving group I metabotropic glutamate (mGlu) receptors. We found
      that in striatal neurons co-cultured with cortical neurons, the absence of
      dopaminergic stimuli favored the excess of glutamatergic drive from cortical
      neuron terminals, thus resulting in a constitutive depression of the
      corticostriatal glutamatergic transmission. Indeed, concomitant blockade of group
      I mGlu receptors and activation of dopaminergic receptors stably reduced the
      depression of the synaptic transmission. Thus the dependence on glutamate and
      dopamine balance of the corticostriatal synapse responsiveness validates the
      accuracy of this manageable in vitro model to depict the molecular pathways
      involved in the plasticity at corticostriatal synapses and to test restorative
      therapeutic approaches in Parkinson's disease. This article is part of a Special
      Issue entitled 'Metabotropic Glutamate Receptors'.

PMID- 22465816
TI  - Pharmacological characterization of 50-kHz ultrasonic vocalizations in rats:
      comparison of the effects of different psychoactive drugs and relevance in drug
      induced reward.
AB  - Significant evidence suggests that ultrasonic vocalizations (USVs) may index the
      emotional state in rats, and 50-kHz USVs have been proposed as a tool to
      investigate the rewarding properties of drugs. Apart from the evidence on some
      psychostimulants, little is known about the effects of other drugs with rewarding
      properties on emission of 50-kHz USVs. To further elucidate the neuropharmacology
      of 50-kHz USVs and their relevance in drug-induced reward, this study
      characterized the effects of different drugs possessing rewarding properties on
      50-kHz USVs in adult male rats. Rats received the acute administration of 3,4
      methylenedioxymethamphetamine (MDMA, 5-15 mg/kg, i.p.), methylphenidate (2.5-10
      mg/kg, i.p.), morphine (1-5 mg/kg, s.c.), or nicotine (0.1-0.4 mg/kg, s.c.). The
      number and acoustic features of 50-kHz USVs and their subtypes were then
      measured. As a comparison, additional rats received the acute administration of
      amphetamine (2 mg/kg, i.p.), which strongly stimulates the emission of 50-kHz
      USVs. Methylphenidate, similar to amphetamine, increased the total number of 50
      kHz USVs emitted by rats, and also modified their acoustic features. Conversely,
      MDMA, morphine, and nicotine did not elevate the total number of 50-kHz USVs.
      However, these drugs modified the acoustic features of 50-kHz USVs, as well as
      the number and acoustic features of specific subtypes of vocalizations. This
      study demonstrates that major differences exist in the effects of psychoactive
      drugs on 50-kHz USVs in rats. These findings provide a better understanding of
      psychoactive properties of drugs with rewarding properties and usefulness of 50
      kHz USVs in assessment of these properties.

PMID- 22465818
TI  - 6-Shogaol, a ginger product, modulates neuroinflammation: a new approach to
      neuroprotection.
AB  - Inflammatory processes in the central nervous system play an important role in a
      number of neurodegenerative diseases mediated by microglial activation, which
      results in neuronal cell death. Microglia act in immune surveillance and host
      defense while resting. When activated, they can be deleterious to neurons, even
      resulting in neurodegeneration. Therefore, the inhibition of microglial
      activation is considered a useful strategy in searching for neuroprotective
      agents. In this study, we investigated the effects of 6-shogaol, a pungent agent
      from Zingiber officinale Roscoe, on microglia activation in BV-2 and primary
      microglial cell cultures. 6-Shogaol significantly inhibited the release of nitric
      oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) induced
      by lipopolysaccharide (LPS). The effect was better than that of 6-gingerol,
      wogonin, or N-monomethyl-l-arginine, agents previously reported to inhibit nitric
      oxide. 6-Shogaol exerted its anti-inflammatory effects by inhibiting the
      production of prostaglandin E(2) (PGE(2)) and proinflammatory cytokines, such as
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and by
      downregulating cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase
      (MAPK), and nuclear factor kappa B (NF-kappaB) expression. In addition, 6-shogaol
      suppressed the microglial activation induced by LPS both in primary cortical
      neuron-glia culture and in an in vivo neuroinflammatory model. Moreover, 6
      shogaol showed significant neuroprotective effects in vivo in transient global
      ischemia via the inhibition of microglia. These results suggest that 6-shogaol is
      an effective therapeutic agent for treating neurodegenerative diseases.

PMID- 22465817
TI  - Ivermectin reduces alcohol intake and preference in mice.
AB  - The high rate of therapeutic failure in the management of alcohol use disorders
      (AUDs) underscores the urgent need for novel and effective strategies that can
      deter ethanol consumption. Recent findings from our group showed that ivermectin
      (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety
      profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4
      receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to
      hypothesize that IVM may reduce alcohol consumption; thus, in the present study
      we investigated the effects of this agent on several models of alcohol self
      administration in male and female C57BL/6 mice. Overall, IVM (1.25-10 mg/kg,
      intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent
      limited access (4-h) binge drinking, and operant alcohol self-administration (1
      h). The effects on alcohol intake were dose-dependent with the significant
      reduction in intake at 9 h after administration corresponding to peak IVM
      concentrations (C(max)) in the brain. IVM also produced a significant reduction
      in 24-h saccharin consumption, but did not alter operant sucrose self
      administration. Taken together, the findings indicate that IVM reduces alcohol
      intake across several different models of self-administration and suggest that
      IVM may be useful in the treatment of AUDs.

PMID- 22465819
TI  - Macular epiretinal brachytherapy in treated age-related macular degeneration:
      MERITAGE study: twelve-month safety and efficacy results.
AB  - PURPOSE: To evaluate the safety and efficacy of epimacular brachytherapy (EMB)
      for the treatment of chronic, active, neovascular age-related macular
      degeneration (AMD). DESIGN: Prospective, multicenter, interventional,
      noncontrolled clinical trial. PARTICIPANTS: Fifty-three eyes of 53 participants
      with neovascular AMD requiring frequent anti-vascular endothelial growth factor
      (VEGF) retreatment. METHODS: Participants underwent pars plana vitrectomy with a
      single 24-Gy dose of EMB delivered using an intraocular, handheld cannula
      containing a strontium 90/yttrium 90 source positioned over the active lesion.
      Participants were retreated with ranibizumab administered monthly as needed,
      using predefined retreatment criteria. Optical coherence tomography (OCT) was
      undertaken monthly, with images assessed by an independent reading center. MAIN
      OUTCOME MEASURES: Coprimary outcomes at 12 months were proportion of participants
      with stable vision (losing <15 Early Treatment Diabetic Retinopathy Study [ETDRS]
      letters) and mean number of anti-VEGF retreatments. RESULTS: Before enrollment,
      participants had received an average of 12.5 anti-VEGF injections. After a single
      treatment with EMB, 81% maintained stable vision, with a mean of 3.49 anti-VEGF
      retreatments in 12 months. Mean +/- standard deviation change in visual acuity
      was -4.0+/-15.1 ETDRS letters. Mean +/- standard deviation OCT central retinal
      thickness increased by 50+/-179 MUm. Common adverse events included conjunctival
      hemorrhage (n = 38), cataract (n = 16), resolving vitreous hemorrhage (n = 6),
      and eye pain (n = 5). CONCLUSIONS: Epimacular brachytherapy produces stable
      visual acuity in most participants with previously treated, active disease.
      Epimacular brachytherapy may reduce the need for frequent anti-VEGF retreatment.

PMID- 22465820
TI  - There is significant load sharing and physical interaction between the
      anteromedial and posterolateral bundles of the ovine ACL under anterior tibial
      loads.
AB  - INTRODUCTION: The ovine stifle joint is an ideal preclinical model to test the
      ability of double-bundle reconstruction techniques in providing superior joint
      stability and less osteoarthritis (OA) compared with single-bundle techniques.
      However, knowledge of the normal ovine ACL and more specifically the load sharing
      and physical interaction between the two main bundles of the ovine ACL is
      currently limited. METHODS: Six ovine stifle joints were tested using a robotic
      testing system. Each joint was cyclically loaded to 200N in the anterior tibial
      direction between 30 degrees  and 90 degrees  flexion and the force-displacement
      data were recorded for both the intact ACL, and when the anteromedial (AM, n=3)
      or the posterolateral bundle (PL, n=3) was transected. RESULTS: The load shared
      by the AM bundle increased from 30 degrees  to 75 degrees  of flexion at all
      loading levels (25-200N); whereas, the load shared by the PL bundle decreased
      between full extension and mid flexion (60 degrees ) and then increased again.
      The load borne by the AM bundle did not change in response to increasing Anterior
      Tibial Loads (ATL) at each flexion angle, in contrast to the PL bundle (P=0.004).
      Physical interaction between bundles was greatest at 60 degrees  and under 50N
      ATL. CONCLUSION: These data will help create double-bundle ACL reconstructions in
      sheep which are functionally similar to intact native ACL. In turn, this model
      can be used to examine the success of anatomically accurate double-bundle
      reconstructions to prevent the development of OA. LEVEL OF EVIDENCE: III.

PMID- 22465822
TI  - Isotype and glycoform selection for antibody therapeutics.
AB  - We live in a hostile environment but are protected by the innate and adaptive
      immune system. A major component of the latter is mediated by antibody molecules
      that bind to pathogens, with exquisite specificity, and the immune complex formed
      activates cellular mechanisms leading to the removal and destruction of the
      complex. Five classes of antibody are identified; however, the IgG class
      predominates in serum and a majority of monoclonal antibody (mAb) therapeutics
      are based on the IgG format. Selection within the antibody repertoire allows the
      generation of (mAb) having specificity for any selected target, including human
      antigens. This review focuses on the structure and function of the Fc region of
      IgG molecules that mediates biologic functions, within immune complexes, by
      interactions with cellular Fc receptors (FcgammaR) and/or the C1q component of
      complement. A property of IgG that is suited to its use as a therapeutic is the
      long catabolic half life of ~21 days, mediated through the structurally distinct
      neonatal Fc receptor (FcRn). Our understanding of structure/function
      relationships is such that we can contemplate engineering the IgG-Fc to enhance
      or eliminate biologic activities to generate therapeutics considered optimal for
      a given disease indication. There are four subclasses of human IgG that exhibit
      high sequence homology but a unique profile of biologic activities. The FcgammaR
      and the C1q binding functions are dependent on glycosylation of the IgG-Fc.
      Normal human serum IgG is comprised of multiple glycoforms and biologic
      activities, other than catabolism, varies between glycoforms.

PMID- 22465821
TI  - Specificity of fear and disgust experienced during traumatic interpersonal
      victimization in predicting posttraumatic stress and contamination-based
      obsessive-compulsive symptoms.
AB  - Emerging evidence has documented comorbidity between posttraumatic stress
      disorder (PTSD) and obsessive-compulsive disorder (OCD) among individuals with a
      history of traumatic events. There is growing recognition of the importance of
      disgust in each of these conditions independently. No study, however, has
      examined the potential role of disgust in these conditions following traumatic
      event exposure. The current study examined the unique role of peritraumatic fear,
      self-focused disgust, and other-focused disgust in predicting posttraumatic
      stress symptoms and contamination-based OC symptoms among 49 adult women
      (M(age)=28.37, SD=13.86) with a history of traumatic interpersonal victimization.
      Results demonstrated that intensity of peritraumatic self-focused disgust was
      significantly related to contamination-based OC symptoms while peritraumatic fear
      and other-focused disgust were related to posttraumatic stress symptoms. These
      results highlight the need for future research aimed at elucidating the nature of
      the association between disgust experienced during traumatic events and
      subsequent psychopathology.

PMID- 22465823
TI  - Interactions of two O-phosphorylresveratrol derivatives with model membranes.
AB  - The hydrosoluble resveratrol derivative 3-O-phosphorylresveratrol was shown to be
      more cytotoxic against DU 145 prostate cancer cells than its analog 4'-O
      phosphorylresveratrol. In an attempt to unveil the molecular determinants that
      lye at the root of their different biological effects, here we investigate the
      interactions of the two resveratrol derivatives with DMPC model membranes by
      using DSC, membrane permeation/poration assays and molecular dynamics. The
      results show that the 3-O-derivative interacts with DMPC membranes and diffuses
      across them. The 4'-O-derivative lies preferentially onto the surface of
      membrane. The MD simulations provide a molecular interpretation of the
      experiments and highlight that, in order to maximize the apolar interactions, the
      3-O-derivative is embedded in the lipid hydrophobic region. This topographical
      position of the 3-O resveratrol analog perturbs the liquid-crystalline order of
      the lipid bilayer promoting membrane curvature and partial lipid loss from the
      vesicle. This finding reconciles with the lowering of the enthalpy of the lipid
      phase transition and the ability of the molecule to diffuse across membranes. The
      present data contribute to explain the different biological activity of the two
      molecules and evidence that membrane permeability is a key requirement for
      effective design of resveratrol derivatives to be used for therapeutic purposes.

PMID- 22465824
TI  - Rare localization of extrarenal nephroblastoma in 1-month-old female infant.
AB  - Extrarenal occurrence of Wilms' tumor is exceptional and the diagnosis is almost
      always made after surgery. The exact mechanism whereby a Wilms' tumor occurs in
      extrarenal tissue is unknown. The tumor is most commonly located in the
      retroperitoneum or inguinal region. Localization in subcutaneous tissue is
      extremely rare. In this paper, the case of a 1-month-old female infant with an
      extrarenal Wilms' tumor located in the lumbosacral region is presented. Surgical
      excision is the treatment of choice, and the same general therapeutic rules
      should be followed as when the kidney is affected.

PMID- 22465825
TI  - Immunohistopathologic demonstration of deleterious effects on growing rat testes
      of radiofrequency waves emitted from conventional Wi-Fi devices.
AB  - OBJECTIVE: To investigate effects on rat testes of radiofrequency radiation
      emitted from indoor Wi-Fi Internet access devices using 802.11.g wireless
      standards. METHODS: Ten Wistar albino male rats were divided into experimental
      and control groups, with five rats per group. Standard wireless gateways
      communicating at 2.437 GHz were used as radiofrequency wave sources. The
      experimental group was exposed to radiofrequency energy for 24 h a day for 20
      weeks. The rats were sacrificed at the end of the study. Intracardiac blood was
      sampled for serum 8-hydroxy-2'-deoxyguanosine levels. Testes were removed and
      examined histologically and immunohistochemically. Testis tissues were analyzed
      for malondialdehyde levels and prooxidant-antioxidant enzyme activities. RESULTS:
      We observed significant increases in serum 8-hydroxy-2'-deoxyguanosine levels and
      8-hydroxyguanosine staining in the testes of the experimental group indicating
      DNA damage due to exposure (p < 0.05). We also found decreased levels of catalase
      and glutathione peroxidase activity in the experimental group, which may have
      been due to radiofrequency effects on enzyme activity (p < 0.05). CONCLUSIONS:
      These findings raise questions about the safety of radiofrequency exposure from
      Wi-Fi Internet access devices for growing organisms of reproductive age, with a
      potential effect on both fertility and the integrity of germ cells.

PMID- 22465826
TI  - Impact of computerized physician order entry on medication errors.
AB  - BACKGROUND: Information is scarce on the impact of the clinical electronic record
      on the frequency and severity of medication errors in acute geriatric patients.
      MATERIAL AND METHODS: An analytical and descriptive pre-post study was conducted
      on the implementation of computerized provider order entry systems (CPOE), over a
      6 year period. A voluntary reporting system was used to detect the medication
      errors using the IR2 report form of the UK National Health Service, the Global
      Trigger Tool and the walk rounds with the Pharmacy Service. The severity
      categories were taken from the National Coordinating Council for Medication Error
      Reporting and Prevention (NCC MERP) Index Categorizing Errors. RESULTS: A total
      of 1887 medication errors (1553 patients) were detected in the period of study,
      and represented the first adverse event reported (29.3%). 8.5 adverse events per
      100 admissions were found (0.24 in the categories E through I) and the
      prescription errors represented a 27.6%. By drugs dispensed, adverse events were
      2.07 times more frequent in the 3 year period (2007-2009) with electronic
      clinical record than in the 3 year period with the hand-written system (2004
      2006), being more frequent with antibiotics (1.92 times), antipyretic (2.21
      times) and opiates (2.72 times). For serious errors and by doses dispensed, there
      were 5.18 times less frequent serious errors in the period related to the
      electronic record, drug omission (46.8 times less frequent), wrong dose (10.53
      times) and antibiotics (10.84 times). CONCLUSION: Frequent medication errors were
      found in acute geriatric patients. An increase in medication errors and a decline
      in the severity of the detected errors were found in relationship to the
      electronic clinical record. For these reasons, the implementation of the
      electronic clinical record should be monitored.

PMID- 22465827
TI  - Euglycaemic ketoacidosis in a patient with gestational diabetes.

PMID- 22465828
TI  - Uterine tumor with neuroectodermal differentiation of advanced stage managed
      successfully with multimodal strategy.

PMID- 22465829
TI  - Metformin and pancreatic cancer: a clue requiring investigation.
AB  - Laboratory models show antineoplastic activity of metformin under certain
      conditions, and pharmacoepidemiologic studies have reported reduced cancer burden
      among diabetics taking metformin. Therefore, the hypothesis that metformin has
      antineoplastic activity is receiving increasing attention. However, gaps in
      knowledge must be addressed before metformin can be "repurposed" for oncologic
      indications.

PMID- 22465830
TI  - Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the
      mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family
      tumors.
AB  - PURPOSE: Temsirolimus was combined with cixutumumab, a fully human IgG1
      monoclonal antibody directed at the insulin growth factor-1 receptor (IGF-1R).
      EXPERIMENTAL DESIGN: Patients received cixutumumab, 6 mg/kg i.v. weekly, and
      temsirolimus, 25 to 37.5 mg i.v. weekly (4-week cycles), with restaging after 8
      weeks. Median follow-up was 8.9 months. RESULTS: Twenty patients [17 with Ewing's
      sarcoma (EWS), 3 with desmoplastic small-round cell tumor (DSRCT)] were enrolled.
      Twelve patients (60%) were men with a median age of 24 years and six median prior
      systemic therapies in a metastatic setting. The most frequent toxicities were
      thrombocytopenia (85%), mucositis (80%), hypercholesterolemia (75%),
      hypertriglyceridemia (70%), and hyperglycemia (65%; mostly grade I-II). Seven of
      20 patients (35%) achieved stable disease (SD) for more than 5 months or
      complete/partial (CR/PR) responses. Tumor regression of more than 20% (23%, 23%,
      27%, 100%, 100%) occurred in five of 17 (29%) patients with EWS, and they
      remained on study for 8 to 27 months. One of six patients with EWS who previously
      developed resistance to a different IGF-1R inhibitor antibody achieved a CR. Four
      of the seven best responders developed grade III mucositis, myelosuppression, or
      hyperglycemia, which were controlled while maintaining drug dose. CONCLUSION:
      Cixutumumab combined with temsirolimus was well-tolerated and showed preliminary
      evidence of durable antitumor activity in heavily pretreated EWS family tumors.

PMID- 22465831
TI  - Metformin use is associated with better survival of diabetic patients with
      pancreatic cancer.
AB  - PURPOSE: Accumulating evidence suggests that metformin has antitumor activity.
      The aim of this study was to determine whether metformin use has a survival
      benefit in patients with pancreatic cancer. EXPERIMENTAL DESIGN: We conducted a
      retrospective study of patients with diabetes and pancreatic cancer treated at
      The University of Texas MD Anderson Cancer Center (Houston, TX). Information on
      diabetes history, including treatment modalities and clinical outcome of
      pancreatic cancer, was collected using personal interviews and medical record
      review. Survival analysis was carried out using a Kaplan-Meier plot, log-rank
      test, and Cox proportional hazards regression models. RESULTS: Among the 302
      patients identified, there were no significant differences in demographic or
      major clinical characteristics between the patients who had received metformin (n
      = 117) and those who had not (n = 185). The 2-year survival rate was 30.1% for
      the metformin group and 15.4% for the non-metformin group (P = 0.004; chi(2)
      test). The median overall survival time was 15.2 months for the metformin group,
      and 11.1 months for the non-metformin group (P = 0.004, log-rank test). Metformin
      users had a 32% lower risk of death; the HR (95% confidence interval) was 0.68
      (0.52-0.89) in a univariate model (P = 0.004), 0.64 (0.48-0.86) after adjusting
      for other clinical predictors (P = 0.003), and 0.62 (0.44-0.87) after excluding
      insulin users (P = 0.006). Metformin use was significantly associated with longer
      survival in patients with nonmetastatic disease only. CONCLUSIONS: Our finding
      that metformin use was associated with improved outcome of patients with diabetes
      and pancreatic cancer should be confirmed in independent studies. Future research
      should prospectively evaluate metformin as a supplemental therapy in this
      population.

PMID- 22465832
TI  - Tumor hypoxia predicts biochemical failure following radiotherapy for clinically
      localized prostate cancer.
AB  - PURPOSE: Tumor hypoxia is an important determinant of outcome in many human
      malignancies and is associated with treatment resistance and metastases. The aim
      of this study was to determine the effect of hypoxia in patients with prostate
      cancer treated with radiotherapy. EXPERIMENTAL DESIGN: Tumor hypoxia was measured
      in 247 patients with clinically localized prostate cancer before radiotherapy,
      with or without hormonal therapy. The median pO(2) was 6.8 mm Hg and the median
      hypoxic percentage less than 10 mm Hg (HP(10)) was 63%. The median follow-up was
      6.6 years. RESULTS: The 5-year biochemical relapse-free rate (bRFR) was 78%.
      Prostrate-specific antigen and Gleason score were both associated with
      biochemical relapse and formed a baseline clinical model. The effect of hypoxia
      was found to vary with the duration of patient follow-up. HP(10), when added to
      the clinical model, was an independent predictor of early bRFR (P = 0.019). The
      relationship between hypoxia and early bRFR was more pronounced when the analysis
      was restricted to 142 patients with bulk tumor at the site of the oxygen
      measurements (P = 0.004). Hypoxia was the only factor predictive of local
      recurrence in 70 patients who had biopsies conducted during follow-up (P =
      0.043), again with the effect being greatest early after completing treatment.
      CONCLUSIONS: This is the largest clinical study of prostate cancer hypoxia with
      direct measurement of tumor oxygen levels. It shows that hypoxia is associated
      with early biochemical relapse after radiotherapy and also with local recurrence
      in the prostate gland.

PMID- 22465833
TI  - Mechanism of apoptotosis induced by ortho-topolin riboside in human hepatoma cell
      line SMMC-7721.
AB  - The naturally occurring cytokinin, ortho-topolin riboside (oTR), has been
      recently reported to have a strong anticancer effect. However, the molecular
      mechanism has not been elucidated. From our research we found that oTR strongly
      inhibited the proliferation of SMMC-7721 cells inducing apoptosis. After oTR
      treatment, up-regulation of the protein levels of pro-apoptotic Bax and the down
      regulation of the anti-apoptotic proteins, Bcl-2 and Bcl-xL was observed, leading
      to the loss of mitochondrial membrane potential, the release of cytochrome c from
      the mitochondria into the cytosol, the downstream activation of caspase-9 and
      caspase-3, as well as the cleavage of poly ADP-ribose-polymerase (PARP), the
      effect of apoptosis could be blocked by the pan-specific caspase inhibitor z-VAD
      fmk and caspase-9-specific inhibitor z-LEHD-fmk. Moreover, oTR was shown to
      inhibit the activation of the extracellular signal-regulated kinase-1/2
      (ERK(1/2)) as well as the Akt pathway. These results suggest that oTR interferes
      with the mitogen-activated protein kinase (MAPK) and Akt pathways and induces the
      apoptosis of human SMMC-7721 cells through the activation of intrinsic
      mitochondria-mediated pathways. However, the apoptosis was completely prevented
      when cells were treated with A-134974, an inhibitor of adenosine kinase, it
      indicated that the intracellular phosphorylation of oTR is necessary for its
      cytotoxic effects to SMMC-7721 cells.

PMID- 22465834
TI  - Neuroprotective and anti-inflammatory effects of flavonoids isolated from Rhus
      verniciflua in neuronal HT22 and microglial BV2 cell lines.
AB  - The neuroprotective and anti-inflammatory activities of the methanolic extract of
      Rhus verniciflua Stokes (Anacardiaceae) were investigated with mouse hippocampal
      and microglial cells. Bioactivity-guided isolation yielded 10 flavonoids
      including fustin (1), fisetin (2), sulfuretin (3), butein (4), butin (5),
      eriodictyol (6), morin hydrate (7), quercetin (8), kaempferol (9) and
      isoliquiritigenin (10). Among the isolated flavonoids, compounds 2-5
      significantly protected the murine hippocampal HT22 cells against glutamate
      induced neurotoxicity and attenuated reactive oxygen species (ROS) generations.
      In addition, these flavonoids significantly maintained antioxidative defense
      systems preserving the activities of superoxide dismutase (SOD), glutathione
      reductase (GR), glutathione peroxidase (GSH-Px) and the content of glutathione
      (GSH) decreased by glutamate insult. These compounds also showed significant
      inhibitory effects on LPS-induced nitric oxide (NO) production in BV2 cells.
      Especially, compound 4 dose-dependently suppressed the expression of both
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These
      results suggest that these flavonoids possess therapeutic potentials as a
      multipotent agent against neurodegenerative diseases related to oxidative stress
      and pathological inflammatory responses.

PMID- 22465835
TI  - Comparison of murine anorectic responses to the 8-ketotrichothecenes 3
      acetyldeoxynivalenol, 15-acetyldeoxynivalenol, fusarenon X and nivalenol.
AB  - While induction of food refusal by the trichothecene mycotoxin deoxynivalenol
      (DON) has been described in several animal models, much less is known about the
      anorectic effects of structurally related 8-ketotrichothecenes, 3
      acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X
      (FX) and nivalenol (NIV). Here, we compared the capacities of these congeners to
      induce anorexia in the mouse. As previously observed for DON, anorectic responses
      to 3-ADON and 15-ADON in the B6C3F1 female mouse following both intraperitoneal
      (IP) and oral exposure were transient, lasting only a few hours, with food intake
      recovering to control levels within 16 h. For both ADONs, the no observed adverse
      effect levels (NOAEL) and lowest observed adverse effect levels (LOAEL) were 0.5
      and 1mg/kg bw following IP exposure, respectively, and 1 and 2.5mg/kg bw after
      oral exposure, respectively. In contrast, food refusal persisted from 48 to 96 h
      following IP and oral exposure to FX and NIV. For both IP and oral FX exposure,
      the NOAEL was 0.025 mg/kg bw and LOAEL was 0.25mg/kg bw, whereas the NOAELs and
      LOAELs for NIV were 0.01 and 0.1mg/kg bw, respectively, after IP exposure and 0.1
      and 1mg/kg bw, respectively, following oral exposure. Both these data and a prior
      DON study suggest that anorectic responses to 8-ketotrichothecenes were always
      greater when administered IP as compared to oral exposure and follow an
      approximate rank order of NIV>FX>DON~3-ADON~15-ADON for IP exposure and
      FX>NIV>DON~3-ADON~15-ADON for oral exposure. Toxic potency data such as is
      described here will be applicable to future comparative risk assessments for this
      important group of trichothecene mycotoxins.

PMID- 22465836
TI  - Automation of an in vitro cytotoxicity assay used to estimate starting doses in
      acute oral systemic toxicity tests.
AB  - Application of High Throughput Screening (HTS) to the regulatory safety
      assessment of chemicals is still in its infancy but shows great promise in terms
      of facilitating better understanding of toxicological modes-of-action, reducing
      the reliance on animal testing, and allowing more data-poor chemicals to be
      assessed at a reasonable cost. To promote the uptake and acceptance of HTS
      approaches, we describe in a stepwise manner how a well known cytotoxicity assay
      can be automated to increase throughput while maintaining reliability. Results
      generated with selected reference chemicals compared very favourably with data
      obtained from a previous international validation study concerning the prediction
      of acute systemic toxicity in rodents. The automated assay was then included in a
      formal ECVAM validation study to determine if the assay could be used for binary
      classification of chemicals with respect to their acute oral toxicity, using a
      threshold equivalent to a dose of 2000 mg/kg b.w. in a rodent bioassay (LD50).
      This involved the blind-testing of 56 reference chemicals on the HTS platform to
      produce concentration-response and IC50 data. Finally, the assay was adapted to a
      format more suited to higher throughput testing without compromising the quality
      of the data obtained.

PMID- 22465837
TI  - Earlier predictors of eating disorder symptoms in 9-year-old children. A
      longitudinal study.
AB  - The aim of the study was to examine predictors of eating disorder symptoms in a
      population based sample at the earliest age at which they can be measured using
      the Children's Eating Attitudes Test. Data were collected from the longitudinal
      Gateshead Millennium Study cohort; 609 children participated in the 7 year data
      sweep (and their mothers and teachers), and 589 children participated in the 9
      year data sweep. Eating disorder symptoms at 9 years were higher in boys, and in
      children from more deprived families. Higher eating disorder symptoms were
      associated with more body dissatisfaction at 9 years. Higher symptoms were
      predicted by higher levels of dietary restraint and of emotional symptoms, but
      not greater body dissatisfaction, 2 years earlier. The study showed that some
      correlates of high eating disorder symptoms found in adolescents and adults are
      also found in children, before the rise in diagnosable eating disorders over the
      pubertal period.

PMID- 22465838
TI  - A stochastic model for the development of Bateson-Dobzhansky-Muller
      incompatibilities that incorporates protein interaction networks.
AB  - Speciation is characterized by the development of reproductive isolating barriers
      between diverging groups. Intrinsic post-zygotic barriers of the type envisioned
      by Bateson, Dobzhansky, and Muller are deleterious epistatic interactions among
      loci that reduce hybrid fitness, leading to reproductive isolation. The first
      formal population genetic model of the development of these barriers was
      published by Orr in 1995, and here we develop a more general model of this
      process by incorporating finite protein-protein interaction networks, which
      reduce the probability of deleterious interactions in vivo. Our model shows that
      the development of deleterious interactions is limited by the density of the
      protein-protein interaction network. We have confirmed our analytical predictions
      of the number of possible interactions given the number of allele substitutions
      by using simulations on the Saccharomyces cerevisiae protein-protein interaction
      network. These results allow us to define the rate at which deleterious
      interactions are expected to form, and hence the speciation rate, for any protein
      protein interaction network.

PMID- 22465839
TI  - A kinetic model of troponin dissociation in relation to thin filament regulation
      in striated muscle.
AB  - The apparent rate of troponin (Tn) dissociation from myofibrils has been used as
      a method to study thin filament regulation in striated muscle. The rate is
      dependent upon calcium and strong crossbridges and supports the three-state model
      for thin filament regulation. The dissociation rate of Tn is extremely low so it
      is not intuitively clear that such a slow process would probe thin filament
      regulation. We have investigated this issue by developing a simple kinetic model
      to explain the Tn dissociation rate measured by labeled Tn exchange in the
      myofibrils. Tn is composed of three interacting subunits, TnC, TnI and TnT. In
      our model, TnI's regulatory domain switches from actin-tropomyosin to TnC
      followed by TnT dissociation from actin-tropomyosin. This TnI regulatory domain
      switching is linked to the transition of the thin filament from the blocked state
      to the closed state. It is calcium dependent and several orders of magnitude
      faster than TnT dissociation from actin-tropomyosin. By integrating the
      dimensionless rate equations of this model, we have computed the time course of
      each of the various components. In our numerical simulations, the rate constant
      for TnI switching from actin-tropomyosin to TnC was varied from 10 s-1 to 1000 s
      1 to simulate the low calcium, blocked state to high calcium, closed state. The
      computed progress curves for labeled Tn exchange into the myofibrils and the
      derived intensity ratio between the non-overlap and overlap regions well explains
      the intensity ratio progress curves observed experimentally. These numerical
      simulations and experimental observations reveal that the apparent rate of Tn
      dissociation probes the blocked state to closed state equilibrium of the
      myofibrillar thin filament.

PMID- 22465842
TI  - An fMRI study of reduced perceptual load-dependent modulation of task-irrelevant
      activity in adults with autism spectrum conditions.
AB  - Recent studies on selective attention have demonstrated that the perceptual load
      of a task determines the processing stage at which irrelevant sensory stimuli are
      filtered out. Although individuals with autism spectrum conditions (ASC) have
      been repeatedly reported to display several kinds of abnormal behavior related to
      attention deficits, the neural mechanisms underlying these deficits have not been
      well investigated within the framework of the load dependency of selective
      attention. The present study used functional magnetic resonance imaging (fMRI) to
      examine the brain responses of adults with high-functioning ASC to irrelevant
      visual distractors while performing a visual target detection task under high or
      low perceptual load. We observed that the increased perceptual load activated
      regions of the fronto-parietal attention network of controls and ASC comparably.
      On the other hand, the visual cortex activity evoked by visual distractors was
      less modulated by the increased perceptual load in ASC than in controls. Simple
      regression analyses showed that the degree of the modulation was significantly
      correlated with the severity of the autistic symptoms. We also observed reduced
      load-dependent modulation of the functional connectivity between the
      intraparietal and visual regions in the ASC group. These results revealed neural
      correlates for abnormal perceptual load-dependent engagement of visual attention
      in ASC, which may underlie aspects of cognitive and behavioral characteristics of
      these disorders.

PMID- 22465841
TI  - Evidence for coordinated functional activity within the extended amygdala of non
      human and human primates.
AB  - Neuroanatomists posit that the central nucleus of the amygdala (Ce) and bed
      nucleus of the stria terminalis (BST) comprise two major nodes of a
      macrostructural forebrain entity termed the extended amygdala. The extended
      amygdala is thought to play a critical role in adaptive motivational behavior and
      is implicated in the pathophysiology of maladaptive fear and anxiety. Resting
      functional connectivity of the Ce was examined in 107 young anesthetized rhesus
      monkeys and 105 young humans using standard resting-state functional magnetic
      resonance imaging (fMRI) methods to assess temporal correlations across the
      brain. The data expand the neuroanatomical concept of the extended amygdala by
      finding, in both species, highly significant functional coupling between the Ce
      and the BST. These results support the use of in vivo functional imaging methods
      in nonhuman and human primates to probe the functional anatomy of major brain
      networks such as the extended amygdala.

PMID- 22465843
TI  - The influence of emotional priming on the neural substrates of memory: a
      prospective fMRI study using portrait art stimuli.
AB  - Events coupled with an emotional context seem to be better retained than non
      emotional events. The aim of our study was to investigate whether an emotional
      context could influence the neural substrates of memory associations with novel
      portrait art stimuli. In the current prospective fMRI study, we have investigated
      for one specific visual art form (modern artistic portraits with a high degree of
      abstraction) whether memory is influenced by priming with emotional facial
      pictures. In total forty healthy female volunteers in the same age range were
      recruited for the study. Twenty of these women participated in a prospective
      brain imaging memory paradigm and were asked to memorize a series of similar
      looking, but different portraits. After randomization, for twelve participants
      (Group 1), a third of the portraits was emotionally primed with approach-related
      pictures (smiling baby faces), a third with withdrawal-related pictures (baby
      faces with severe dermatological conditions), and another third with neutral
      images. Group 2 consisted of eight participants and they were not primed. Then,
      during an fMRI session 2h later, these portraits were viewed in random order
      intermixed with a set of new (previously unseen) ones, and the participants had
      to decide for each portrait whether or not they had already been seen. In a
      separate experiment, a different sample of twenty healthy females (Group 3) rated
      their mood after being exposed to the same art stimuli, without priming. The
      portraits did not evoke significant mood changes by themselves, supporting their
      initial neutral emotional character (Group 3). The correct decision on whether
      the portraits were Familiar of Unfamiliar led to similar neuronal activations in
      brain areas implicated in visual and attention processing for both groups (Groups
      1 and 2). In contrast, whereas primed participants showed significant higher
      neuronal activities in the left midline superior frontal cortex (Brodmann area
      (BA) 6), unprimed volunteers displayed higher right medial frontal cortical (BA
      10) activities. Furthermore, specifically in Group 1, correct retrieval of
      negatively primed portraits evoked increased neuronal activity in the left medial
      orbitofrontal cortex (BA 11) and in the right (posterior) insula, suggesting
      enhanced stress-related responses to the memory of withdrawal-related primed
      modern artistic portraits in this group. Our prospective memory data in healthy
      females indicate that, to reach a correct retrieval decision, different midline
      anterior neuronal networks are recruited for portraits that were emotionally
      primed than for the unprimed ones. Importantly, our results also suggest that the
      negative emotional context leads to the formation of associations that are
      reactivated during memory retrieval processes of the initially neutral art
      portraits. When correctly recognized, the portraits evoke neuronal activities
      consistent with the withdrawal-related character of the emotional visual stimuli
      with which they have been associated. Although our results show that abstract
      portrait art can be associated with emotional primes this doesn't mean that this
      effect is specific for art images.

PMID- 22465844
TI  - Focal cortical damage parallels cognitive impairment in minimal hepatic
      encephalopathy.
AB  - Little attention has been paid to cortical integrity in patients with minimal
      hepatic encephalopathy (MHE), although cognitive functions affected in early
      stages of liver disease are mainly allocated in different neocortical structures.
      Here we used cortical surface-based analysis techniques to investigate if
      patterns of cortical thinning accompany the mildest form of HE. To aim this goal,
      cortical thickness obtained from high-resolution 3T magnetic resonance imaging
      (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls.
      Further correlation analyses were performed to examine whether scores in the
      critical flicker frequency (CFF) test, and blood ammonia levels accounted for the
      loss of cortical integrity in different stages of liver disease. Finally, we
      assessed group differences in volume of different subcortical regions and their
      potential relationships with CFF scores/blood ammonia levels. Results showed a
      focal thinning of the superior temporal cortex and precuneus in MHE patients when
      compared with NMHE and controls. Relationships between blood ammonia levels and
      cortical thickness of the calcarine sulcus accounted for impaired visual judgment
      in patients with MHE when compared to NMHE. Regression analyses between cortical
      thickness and CFF predicted differences between controls and the two groups of HE
      patients, but failed to discriminate between patients with NMHE and MHE. Taking
      together, these findings provide the first report of cortical thinning in MHE
      patients, and they yield novel insights into the neurobiological basis of
      cognitive impairment associated with early stages of liver diseases.

PMID- 22465845
TI  - In vivo hydroquinone exposure impairs MCP-1 secretion and monocyte recruitment
      into the inflamed lung.
AB  - Alveolar macrophages (AMs) are important cells in the resolution of the
      inflammatory process and they come into direct contact with inhaled pollutants.
      Hydroquinone (HQ) is an environmental pollutant and a component of cigarette
      smoke that causes immunosuppressive effects. In the present work, we showed that
      mice exposed to low levels of aerosolized HQ (25 ppm; 1 h/day/5 days) presented
      impaired mononuclear cell migration to the lipopolysaccharide (LPS)-inflamed
      lung. This may have been due to reduced monocyte chemoattractant protein-1 (MCP
      1) secretion into bronchoalveolar lavage fluid (BALF), and it was not related to
      alterations to mononuclear cell mobilization into the blood or adhesion molecules
      expression on mononuclear cell membranes. Corroborating the actions of HQ on MCP
      1 secretion, reduced MCP-1 concentrations were also found in the supernatant of
      ex vivo AM and tracheal tissue collected from HQ-exposed mice. A direct action of
      HQ on MCP-1 secretion, resulting from impaired gene synthesis, was verified by in
      vitro incubation of naive AMs or tracheal tissue with HQ. The role of reduced
      levels of MCP-1 in the BALF on monocyte migration was analysed in the human
      monocytic lineage THP-1 in in vitro chemotaxis assays, which showed that the
      reduced concentrations of MCP-1 found in the BALF or cell supernatants from HQ
      exposed mice impaired cell migration. Considering the fact that MCP-1 presents a
      broad spectrum of actions on pathophysiological conditions and that resident
      mononuclear cells are involved in lung tissue homeostasis and in immune host
      defence, the mechanism of HQ toxicity presented herein might be relevant to the
      genesis of infectious lung diseases in smokers and in inhabitants of polluted
      areas.

PMID- 22465846
TI  - Flavour-nutrient learning in humans: an elusive phenomenon?
AB  - One widely cited model of how humans acquire liking for different foods is
      flavour-nutrient learning, where associations between the orosensory properties
      of the ingested food or drink (the flavour CS) and positive consequences of
      nutrient ingestion (the UCS) lead to acquired liking for the flavour (flavour
      nutrient hedonic learning: FNL-H). Likewise, an association between the CS and
      the post-ingestive effects of ingested nutrients has been suggested to lead to
      learning about how satiating a particular food is (flavour-nutrient satiety
      learning: FNSH). However, whereas there is evidence for both FNL-H and FNL-S in
      experimental studies with non-human animals, evidence in humans is less
      convincing, with many failures to find the predicted changes in liking,
      preference or intake following repeated flavour-nutrient pairings. The present
      short review considers how subtle differences in experimental design might
      underlie this inconsistency, and identifies key design features which appear to
      increase the likelihood of success in human flavour-nutrient learning studies.
      Key factors include CS novelty, the level of nutrients ingested during training,
      the appetitive state of the consumer and individual consumer characteristics. A
      further complication is competition between FNL-H and FNL-S, and with other
      associations such as flavour-flavour learning. From this it is possible to make
      important inferences about the nature of human flavour-nutrient learning which
      firstly suggest that it has important similarities to that seen in other species,
      but secondly that the laboratory investigations of both FNL-H and FNL-S in humans
      can be compromised by subtle but important variations in experimental design.

PMID- 22465847
TI  - Iron status and fibroblast growth factor-23 in Gambian children.
AB  - A relationship between iron and fibroblast growth factor-23 (FGF23) metabolic
      pathways has been proposed. Iron deficiency anaemia is prevalent in The Gambia
      and concentrations of fibroblast growth factor-23 FGF23 are elevated in a large
      percentage of Gambian children with rickets-like bone deformity. We speculate
      that low iron status may be involved in the aetiology of Gambian rickets. The aim
      of this study was to determine if there was a relationship between haemoglobin,
      as a marker of iron status, and FGF23 in samples from children with and without a
      history of rickets-like bone deformities in The Gambia. We conducted a
      retrospective analysis of studies carried out from 2006 to 2008 in children from
      a rural community in The Gambia where iron deficiency anaemia is endemic and
      where elevated circulating concentrations of FGF23 have been found. To
      investigate the relationship between circulating FGF23 and haemoglobin
      concentrations we used an age-adjusted linear regression model on data from
      children <18y of age with a family or personal history of rickets-like bone
      deformity (BD) (n=108) and from the local community (LC) (n=382). We found that
      circulating concentration of FGF23 was inversely correlated with haemoglobin
      concentration. This effect was more pronounced in BD children compared with LC
      children (interaction: P<=0.0001). Anaemia and elevated FGF23 were more prevalent
      in BD children compared to LC children (P=0.0003 and P=0.0001 respectively). In
      conclusion, there is a stronger relationship between FGF23 and haemoglobin in
      Gambian children with a history of rickets compared to local community children.
      This study provides support for the contention that iron may be involved in FGF23
      metabolic pathways.

PMID- 22465848
TI  - Arsenic trioxide affects bone remodeling by effects on osteoblast differentiation
      and function.
AB  - Arsenic trioxide (ATO) is widely used in tumor treatment, but excessive arsenic
      exposure can have adverse health effects. This study was to examine the
      association between ATO treatment and bone remodeling. The effects of ATO on
      osteoblast function were investigated in primary cell cultures and in an in vivo
      study in rats. Sprague-Dawley rats (n=30) were randomly assigned to 3 groups
      which were injected intraperitoneally with saline or 5 or 10 mg/kg of ATO for 4
      weeks. In cell culture, ATO decreased osteoblast mineralization by decreasing
      alkaline phosphatase (ALP) expression and this effect was prevented by co
      addition of inorganic phosphate (Pi). Moreover, levels of mRNAs for the
      transcription factors runt-related transcription factor 2 (Runx2) and osterix,
      the osteoblast osteogenic gene osteocalcin, and the adherence molecule vascular
      cell adhesion molecule-1 (VCAM-1) were decreased by ATO. Levels of mRNAs for the
      cytokine IL-6 were also decreased, whereas GM-CSF mRNA levels were increased.
      Similar effects of ATO on osteoblasts were seen in in vivo experiments in the
      rat. Moreover, decreases of bone turnover markers of osteocalcin, Procollagen
      type I N-terminal propeptide (PINP), and C-terminal cross-linked telopeptide
      (CTX) as well as bone mineral density (BMD) and trabecular bone volume of femur
      were observed in ATO-treated rats. These results suggest that ATO interferes with
      bone remodeling mostly through changes in osteoblast differentiation and
      function.

PMID- 22465849
TI  - Chronic exposure to methylphenidate impairs appendicular bone quality in young
      rats.
AB  - Methylphenidate (MP) is a psychostimulant widely prescribed to treat Attention
      Deficit Hyperactivity Disorder (ADHD). Although generally well tolerated, growth
      deficits have been reported in children and adolescents undergoing MP treatment.
      This study was designed to elucidate the skeletal effects of chronic MP
      administration in adolescent rats. Male, 4-week-old rats received one of two
      doses of MP (MP-Low or MP-High) delivered for 8 h a day via drinking water, or
      were untreated (water only). After 13 weeks, half were sacrificed (N=12/group)
      and the remaining rats were left to recover, untreated for 5 additional weeks.
      Femora, tibiae, and L5 vertebra were analyzed using calipers, DXA, and mechanical
      testing. Immediately following treatment, MP decreased femoral anterior-posterior
      diameter (5% and 9% for MP-Low and MP-High, respectively), femoral and tibial
      bone mineral density (BMD) (6% and 5% for MP-High femora and tibiae,
      respectively), and bone mineral content (BMC) (9% for MP-High femora and tibiae).
      In addition, femora from MP treated rats had reduced ultimate force (20% for MP
      High) and energy to failure (20% and 33% for MP-Low and MP-High, respectively).
      However, after recovery, there were no statistically significant differences for
      any measured parameters. Despite these effects on the appendicular skeleton, no
      differences were identified between vertebral samples at either time-point. In
      summary, MP treatment resulted in smaller, less mineralized, and weaker bones at
      appendicular sites, but did not affect the axial site. Although these effects
      were ameliorated within 5 weeks, these data suggest that adolescents undergoing
      MP treatment may be at an increased risk for long bone fractures.

PMID- 22465851
TI  - Enhancing a Pathway-Genome Database (PGDB) to capture subcellular localization of
      metabolites and enzymes: the nucleotide-sugar biosynthetic pathways of Populus
      trichocarpa.
AB  - Understanding how cellular metabolism works and is regulated requires that the
      underlying biochemical pathways be adequately represented and integrated with
      large metabolomic data sets to establish a robust network model. Genetically
      engineering energy crops to be less recalcitrant to saccharification requires
      detailed knowledge of plant polysaccharide structures and a thorough
      understanding of the metabolic pathways involved in forming and regulating cell
      wall synthesis. Nucleotide-sugars are building blocks for synthesis of cell wall
      polysaccharides. The biosynthesis of nucleotide-sugars is catalyzed by a
      multitude of enzymes that reside in different subcellular organelles, and precise
      representation of these pathways requires accurate capture of this biological
      compartmentalization. The lack of simple localization cues in genomic sequence
      data and annotations however leads to missing compartmentalization information
      for eukaryotes in automatically generated databases, such as the Pathway-Genome
      Databases (PGDBs) of the SRI Pathway Tools software that drives much biochemical
      knowledge representation on the internet. In this report, we provide an informal
      mechanism using the existing Pathway Tools framework to integrate protein and
      metabolite sub-cellular localization data with the existing representation of the
      nucleotide-sugar metabolic pathways in a prototype PGDB for Populus trichocarpa.
      The enhanced pathway representations have been successfully used to map SNP
      abundance data to individual nucleotide-sugar biosynthetic genes in the PGDB. The
      manually curated pathway representations are more conducive to the construction
      of a computational platform that will allow the simulation of natural and
      engineered nucleotide-sugar precursor fluxes into specific recalcitrant
      polysaccharide(s). Database URL: The curated Populus PGDB is available in the
      BESC public portal at http://cricket.ornl.gov/cgi-bin/beocyc_home.cgi and the
      nucleotide-sugar biosynthetic pathways can be directly accessed at
      http://cricket.ornl.gov:1555/PTR/new-image?object=SUGAR-NUCLEOTIDES.

PMID- 22465850
TI  - Different effects of age, adiposity and physical activity on the risk of ankle,
      wrist and hip fractures in postmenopausal women.
AB  - While increasing age, decreasing body mass index (BMI), and physical inactivity
      are known to increase hip fracture risk, whether these factors have similar
      effects on other common fractures is not well established. We used prospectively
      collected data from a large cohort to examine the role of these factors on the
      risk of incident ankle, wrist and hip fractures in postmenopausal women.
      1,155,304 postmenopausal participants in the Million Women Study with a mean age
      of 56.0 (SD 4.8) years, provided information about lifestyle, anthropometric, and
      reproductive factors at recruitment in 1996-2001. All participants were linked to
      National Health Service cause-specific hospital records for day-case or overnight
      admissions. During follow-up for an average of 8.3 years per woman, 6807 women
      had an incident ankle fracture, 9733 an incident wrist fracture, and 5267 an
      incident hip fracture. Adjusted absolute and relative risks (RRs) for incident
      ankle, wrist, and hip fractures were calculated using Cox regression models. Age
      specific rates for wrist and hip fractures increased sharply with age, whereas
      rates for ankle fracture did not. Cumulative absolute risks from ages 50 to 84
      years per 100 women were 2.5 (95%CI 2.2-2.8) for ankle fracture, 5.0 (95%CI 4.4
      5.5) for wrist fracture, and 6.2 (95%CI 5.5-7.0) for hip fracture. Compared with
      lean women (BMI<20 kg/m(2)), obese women (BMI>=30 kg/m(2)) had a three-fold
      increased risk of ankle fracture (RR=3.07; 95%CI 2.53-3.74), but a substantially
      reduced risk of wrist fracture and especially of hip fracture (RR=0.57; 0.51-0.64
      and 0.23; 0.21-0.27, respectively). Physical activity was associated with a
      reduced risk of hip fracture but was not associated with ankle or wrist fracture
      risk. Ankle, wrist and hip fractures are extremely common in postmenopausal
      women, but the associations with age, adiposity, and physical activity differ
      substantially between the three fracture sites.

PMID- 22465852
TI  - Children with developmental disabilities at a pediatric hospital: staff education
      to prevent and manage challenging behaviors.
AB  - Children with developmental disabilities may get frustrated in unpredictable
      hospital environments. Frustration may escalate to challenging behaviors, which
      are a safety concern and may contribute to staff and patient injuries, use of
      restraints, and procedure delay or cancelations. The purpose of this article was
      to describe a pilot staff education program on preventing and managing
      challenging behaviors of children with developmental disabilities at a pediatric
      hospital. The 2-hour-long education (1 hour on-line and 1 hour instructor led)
      content focused on family-centered care and communication skills, including
      verbal judoTM modified for use in the health care setting. Participants in the
      instructor-led sessions reported improved knowledge and decreased fear about
      caring for children with developmental disabilities. Relationships of the
      education and fewer staff injuries, fewer canceled procedures, and decreased use
      of restraints merit further study.

PMID- 22465853
TI  - A minimal phycobilisome: fusion and chromophorylation of the truncated core
      membrane linker and phycocyanin.
AB  - Phycobilisomes, the light-harvesting antennas in cyanobacteria and red algae,
      consist of an allophycocyanin core that is attached to the membrane via a core
      membrane linker, and rods comprised of phycocyanin and often also phycoerythrin
      or phycoerythrocyanin. Phycobiliproteins show excellent energy transfer among the
      chromophores that renders them biomarkers with large Stokes-shifts absorbing over
      most of the visible spectrum and into the near infrared. Their application is
      limited, however, due to covalent binding of the chromophores and by solubility
      problems. We report construction of a water-soluble minimal chromophore-binding
      unit of the red-absorbing and fluorescing core-membrane linker. This was fused to
      minimal chromophore-binding units of phycocyanin. After double chromophorylation
      with phycocyanobilin, in E. coli, the fused phycobiliproteins absorbed light in
      the range of 610-660nm, and fluoresced at ~670nm, similar to phycobilisomes
      devoid of phycoerythr(ocyan)in. The fused phycobiliprotein could also be doubly
      chromophorylated with phycoerythrobilin, resulting in a chromoprotein absorbing
      around 540-575nm, and fluorescing at ~585nm. The broad absorptions and the large
      Stokes shifts render these chromoproteins candidates for imaging; they may also
      be helpful in studying phycobilisome assembly.

PMID- 22465854
TI  - Mitochondrial DNA metabolism in early development of zebrafish (Danio rerio).
AB  - Changes in the mitochondrial DNA (mtDNA) population, together with the expression
      of a set of genes involved in mtDNA replication and transcription and genes
      encoding for components of OxPhos complexes, were studied during zebrafish
      development from early embryo to larval stages. The mtDNA copy number, measured
      from 1h post-fertilization to the adult stage, significantly decreased over time,
      suggesting that mtDNA replication is not active in early zebrafish embryos and
      that, as in mammals, there occurs partition of the maternal mtDNA copies.
      Zebrafish genes involved in mtDNA replication (i.e. catalytic subunit of the
      mtDNA polymerase gamma, mitochondrial deoxyribonucleoside kinase) are expressed
      late in embryo development, further supporting the notion that there is no
      replication of mtDNA in the early stages of zebrafish development. Notably, as
      from 4days post-fertilization, marked expression of "replication genes" was
      observed in the exocrine pancreas. Interestingly, the mtDNA helicase, also
      involved in mtDNA replication, was detected early in development, suggesting
      diverse regulation of this gene. On the other hand, zebrafish mtDNA transcription
      genes (i.e. mtDNA-directed RNA polymerase, mitochondrial transcription factor A)
      were ubiquitously expressed in the early stages of development, suggesting that
      mitochondrial transcription is already active before mtDNA replication. This
      hypothesis of early activation of mtDNA transcription fits in with the high early
      expression of structural OxPhos genes, suggesting that an active OxPhos system is
      necessary during early embryogenesis. As well as providing the first description
      of mtDNA distribution during zebrafish development, the present study also
      represents a step toward the use of Danio rerio as a model for investigation of
      mitochondrial metabolism and disease.

PMID- 22465855
TI  - Temperature-dependent vibrational and conformational dynamics of photosystem II
      membrane fragments from spinach investigated by elastic and inelastic neutron
      scattering.
AB  - Vibrational and conformational protein dynamics of photosystem II (PS II)
      membrane fragments from spinach were investigated by elastic and inelastic
      incoherent neutron scattering (EINS and IINS). As to the EINS experiments, the
      average atomic mean square displacement values of PS II membrane fragments
      hydrated at a relative humidity of 57% exhibit a dynamical transition at ~230K.
      In contrast, the dynamical transition was absent at a relative humidity of 44%.
      These findings are in agreement with previous studies which reported a "freezing"
      of protein mobility due to dehydration (Pieper et al. (2008) Eur. Biophys. J. 37:
      657-663) and its correlation with an inhibition of electron transfer from Q(A)(-)
      to Q(B) (Kaminskaya et al. (2003) Biochemistry 42, 8119-8132). IINS spectra of a
      sample hydrated at a relative humidity of 57% show a distinct Boson peak at
      ~7.5meV at 20K, which shifts towards lower energy values upon temperature
      increase to 250K. This unexpected effect is interpreted in terms of a "softening"
      of the protein matrix along with the onset of conformational protein dynamics as
      revealed by the EINS experiments. Information on the density of vibrational
      states of pigment-protein complexes is important for a realistic calculation of
      excitation energy transfer kinetics and spectral lineshapes and is often
      routinely obtained by optical line-narrowing spectroscopy at liquid helium
      temperature. The data presented here demonstrate that IINS is a valuable
      experimental tool in determining the density of vibrational states not only at
      cryogenic, but also at nearly physiological temperatures up to 250K. This article
      is part of a Special Issue entitled: Photosynthesis Research for Sustainability:
      from Natural to Artificial.

PMID- 22465856
TI  - Insights into the mechanism of electron transfer and sodium translocation of the
      Na(+)-pumping NADH:quinone oxidoreductase.
AB  - Na(+)-NQR is a unique energy-transducing complex, widely distributed among marine
      and pathogenic bacteria. It converts the energy from the oxidation of NADH and
      the reduction of quinone into an electrochemical Na(+)-gradient that can provide
      energy for the cell. Na(+)-NQR is not homologous to any other respiratory protein
      but is closely related to the RNF complex. In this review we propose that sodium
      pumping in Na(+)-NQR is coupled to the redox reactions by a novel mechanism,
      which operates at multiple sites, is indirect and mediated by conformational
      changes of the protein. This article is part of a Special Issue entitled: 17th
      European Bioenergetics Conference (EBEC 2012).

PMID- 22465857
TI  - Effects of exposure to the beta-blocker propranolol on the reproductive behavior
      and gene expression of the fathead minnow, Pimephales promelas.
AB  - Human pharmaceutical drugs have been found in surface waters worldwide, and
      represent an increasing concern since little is known about their possible
      effects on wildlife. Propranolol is a common beta-adrenergic receptor antagonist
      (beta-blocker) typically prescribed to people suffering from heart disease and
      hypertension. Propranolol has been detected in United States wastewater effluents
      at concentrations ranging from 0.026 to 1.90 MUg/l. In mammals, there is evidence
      that beta-blockers can cause sexual dysfunction, and alter serotonergic pathways
      which may impact reproductive behavior but little is known about the effects on
      fish behavior. The present study tested the effects of propranolol on fecundity,
      on brain gene expression and on reproductive behavior of the fathead minnow,
      Pimephales promelas, a fish that exhibits male parental care. Sexually mature
      fathead minnows were housed at a ratio of one male and two females per tank and
      exposed to nominal concentrations of 0, 0.1, 1, 10 MUg/l for 21 days. Measured
      concentrations (+/-SD) of propranolol were 0.003+/-0.004, 0.05+/-0.02, 0.88+/
      0.34 and 4.11+/-1.19 MUg/l. There were no statistically significant differences
      in fecundity, fertilization rate, hatchability and time to hatch. Propranolol
      exposure was not associated with a change in nest rubbing behavior, time spent in
      the nest or approaching the females. There was a significant difference in the
      number of visits to the nest with males receiving low and medium propranolol
      treatments. The microarray analysis showed that there were 335 genes up-regulated
      and 400 genes down-regulated in the brain after exposure to the highest dose of
      propranolol. Among those genes, myoglobin and calsequestrin transcripts (fold
      change=10.84 and 5.49, respectively) were highly up-regulated. Ontological
      analyses indicated changes in genes involved in calcium ion transport,
      transcription, proteolysis and apoptosis/anti-apoptosis. Pathway analysis
      indicated that the reduced expression of caspases may lead to impaired neurite
      outgrowth, neurotransmitter secretion and brain function in developing organisms.
      The results showed that exposure to propranolol at concentrations as high as 4.11
      MUg/l did not significantly impact reproductive behavior or spawning abilities of
      fathead minnow but did alter the regulation of genes within the brain of fish.

PMID- 22465858
TI  - An enzymatic glycosylation of nucleoside analogues using beta-galactosidase from
      Escherichia coli.
AB  - A new enzymatic method for the synthesis of beta-galactosides of nucleosides and
      acyclic nucleoside analogues has been developed, using beta-galactosidase from
      Escherichia coli as a catalyst and lactose as a sugar donor. The method is very
      rapid, feasible and last but not least inexpensive. Its applicability has been
      proven for a broad variety of possible substrates with respect to its scaling up
      for preparative use. Five new compounds from a series of nucleoside and acyclic
      nucleoside analogues have been prepared on a scale of several hundred milligrams,
      in all cases revealing very good results of the method concerning the
      reproducibility of the reaction yields and simplicity of the purification
      process.

PMID- 22465859
TI  - Cluster analysis of the DrugBank chemical space using molecular quantum numbers.
AB  - DrugBank (>6000 approved and experimental drugs) was analyzed using molecular
      quantum numbers (MQNs), which are 42 integer value descriptors of molecular
      structure counting atoms, bonds, polar groups and topological features. Principal
      component analysis of MQN-space showed that drugs differ mostly by size (PC1, 67%
      variance) and structural rigidity and polarity (PC2, 18% variance). Twenty-eight
      groups of target specific drugs were recovered by proximity sorting in MQN-space
      as efficiently as by substructure fingerprint (SF) similarity, but in different
      order allowing for lead-hopping relationships not seen in SF similarity.
      Clustering by MQN- or SF-similarity produced very different types of clusters.
      Each of the 28 drug groups spread over different clusters in both MQN- and SF
      clustering, and most clusters contained drugs from different target specific
      groups, showing that structure-based classifications only partially overlap with
      bioactivity. An MQN-browsable version of DrugBank is available at
      www.gdb.unibe.ch.

PMID- 22465860
TI  - Neuronavigated transcranial magnetic stimulation suggests that area V2 is
      necessary for visual awareness.
AB  - The primary visual cortex (V1) has been shown to be critical for visual
      awareness, but the importance of other low-level visual areas has remained
      unclear. To clarify the role of human cortical area V2 in visual awareness, we
      applied transcranial magnetic stimulation (TMS) over V2 while participants were
      carrying out a visual discrimination task and rating their subjective awareness.
      Individual retinotopic maps and modelling of the TMS-induced electric field in
      V1, V2 and V3d ensured that the electric field was at or under the phosphene
      threshold level in V1 and V3d, whereas in V2 it was at the higher suppressive
      level. As earlier shown for the V1, our results imply that also V2 is necessary
      for conscious visual experience. Visual awareness of stimulus presence was
      completely suppressed when the TMS pulse was delivered 44-84 ms after the onset
      of visual stimulus. Visual discrimination and awareness of stimulus features was
      impaired when the TMS pulse was delivered 44-104 ms after the visual stimulus
      onset. These results suggest that visual awareness cannot be generated without an
      intact V2.

PMID- 22465861
TI  - Understanding motor acts and motor intentions in Williams syndrome.
AB  - Williams syndrome (WS) is a rare genetic disorder associated with unusually hyper
      social demeanor and ease with strangers. These personality traits are accompanied
      by difficulties in social interactions, possibly related, at least in part, to a
      difficulty in understanding others' mental states. Studies on mentalizing
      capacities in individuals with WS have often led to contrasting results, some
      studies revealing specific impairments, others highlighting spared mentalizing
      capacities. So far, however, no study investigated the performance of individuals
      with WS in non-inferential understanding of others' motor intentions. In the
      present study we investigated this capacity by using a computer-based behavioral
      task using pictures of hand-object interactions. We asked individuals with WS
      first to describe what the other was doing (i.e. a task implying no kind of
      intention reading), and secondly, if successful in answering the first question,
      to describe the motor intention underlying the observed motor acts (i.e. why an
      act was being done, a task requiring non-inferential motor intention
      understanding). Results showed that individuals with WS made more errors in
      understanding what the other was doing (i.e. understanding a motor act) compared
      to both mental-age matched controls and chronological-age matched peers with
      typical development, while showing mental-age appropriate performance in
      understanding why an individual was acting (i.e. understanding a motor
      intention). These findings suggest novel perspectives for understanding
      impairments in social behavior in WS.

PMID- 22465862
TI  - Transcranial direct current stimulation (tDCS) of the inferior frontal gyrus
      disrupts interpersonal motor resonance.
AB  - Interpersonal motor resonance (IMR) is presumed to result from activity within
      the human mirror neuron system, which itself is thought to comprise the inferior
      parietal lobule (IPL) and inferior frontal gyrus (IFG). Twenty healthy adults
      underwent anodal, cathodal, and sham transcranial direct current stimulation
      (tDCS) to either IPL or IFG immediately before the assessment of IMR (using
      transcranial magnetic stimulation). IMR (i.e., motor-evoked potential amplitude
      during transitive action observation relative to static observation) was
      significantly reduced following both anodal and cathodal stimulation of IFG
      (relative to sham), but there was no effect of stimulation for IPL. These data
      support the role of IFG, a presumed mirror neuron region, in IMR.

PMID- 22465863
TI  - Right frontal cortical lesions disrupt anger mimicry.
AB  - The current study investigates the neural substrates of facial expression mimicry
      by assessing individuals with right and left lateralised frontal cortical
      lesions. Electromyography was used to measure spontaneous changes in electrical
      activity over the corrugator supercilii (brow) and zygomaticus major (cheek)
      muscle regions in response to happy and angry facial expressions. Individuals
      with right (n=4) and left (n=5) frontal cortical lesions and demographically
      matched controls (n=9) were compared. It was shown that while all three groups
      mimic happy facial expressions, only controls and individuals with left frontal
      lesions mimic angry expressions. These data are consistent with evidence for
      right frontal cortical specialisation for the processing of anger.

PMID- 22465866
TI  - Energy deficiency, menstrual disturbances, and low bone mass: what do exercising
      Australian women know about the female athlete triad?
AB  - PURPOSE: Prevention of the female athlete triad is essential to protect female
      athletes' health. The aim of this study was to investigate the knowledge,
      attitudes, and behaviors of regularly exercising adult women in Australia toward
      eating patterns, menstrual cycles, and bone health. METHODS: A total of 191
      female exercisers, age 18-40 yr, engaging in >=2 hr/wk of strenuous activity,
      completed a survey. After 11 surveys were excluded (due to incomplete answers),
      the 180 participants were categorized into lean-build sports (n = 82;
      running/athletics, triathlon, swimming, cycling, dancing, rowing), non-lean-build
      sports (n = 94; basketball, netball, soccer, hockey, volleyball, tennis,
      trampoline, squash, Australian football), or gym/fitness activities (n = 4).
      RESULTS: Mean (+/- SD) training volume was 9.0 +/- 5.5 hr/wk, with participants
      competing from local up to international level. Only 10% of respondents could
      name the 3 components of the female athlete triad. Regardless of reported history
      of stress fracture, 45% of the respondents did not think that amenorrhea (absence
      of menses for >=3 months) could affect bone health, and 22% of those involved in
      lean-build sports would do nothing if experiencing amenorrhea (vs. 3.2% in non
      lean-build sports, p = .005). Lean-build sports, history of amenorrhea, and
      history of stress fracture were all significantly associated with not taking
      action in the presence of amenorrhea (all p < .005). CONCLUSIONS: Few active
      Australian women are aware of the detrimental effects of menstrual dysfunction on
      bone health. Education programs are needed to prevent the female athlete triad
      and ensure that appropriate actions are taken by athletes when experiencing
      amenorrhea.

PMID- 22465867
TI  - Dietary supplements for improving body composition and reducing body weight:
      where is the evidence?
AB  - Weight-loss supplements typically fall into 1 of 4 categories depending on their
      hypothesized mechanism of action: products that block the absorption of fat or
      carbohydrate, stimulants that increase thermogenesis, products that change
      metabolism and improve body composition, and products that suppress appetite or
      give a sense of fullness. Each category is reviewed, and an overview of the
      current science related to their effectiveness is presented. While some weight
      loss supplements produce modest effects (<2 kg weight loss), many have either no
      or few randomized clinical trials examining their effectiveness. A number of
      factors confound research results associated with the efficacy of weight-loss
      supplements, such as small sample sizes, short intervention periods, little or no
      follow-up, and whether the supplement is given in combination with an energy
      restricted diet or increased exercise expenditure. There is no strong research
      evidence indicating that a specific supplement will produce significant weight
      loss (>2 kg), especially in the long term. Some foods or supplements such as
      green tea, fiber, and calcium supplements or dairy products may complement a
      healthy lifestyle to produce small weight losses or prevent weight gain over
      time. Weight-loss supplements containing metabolic stimulants (e.g., caffeine,
      ephedra, synephrine) are most likely to produce adverse side effects and should
      be avoided.

PMID- 22465870
TI  - Restoration of menses with nonpharmacologic therapy in college athletes with
      menstrual disturbances: a 5-year retrospective study.
AB  - BACKGROUND: Functional hypothalamic amenorrhea is common among female athletes
      and may be difficult to treat. Restoration of menses (ROM) is crucial to prevent
      deleterious effects to skeletal and reproductive health. OBJECTIVES: To determine
      the natural history of menstrual disturbances in female college athletes managed
      with nonpharmacologic therapies including increased dietary intake and/or
      decreased exercise expenditure and to identify factors associated with ROM. STUDY
      DESIGN: A 5-yr retrospective study of college athletes at a major Division I
      university. METHODS: 373 female athletes' charts were reviewed. For athletes with
      menstrual disturbances, morphometric variables were noted. Months to ROM were
      recorded for each athlete. RESULTS: Fifty-one female athletes (19.7%) had
      menstrual disturbances (14.7% oligomenorrheic, 5.0% amenorrheic). In all, 17.6%
      of oligo-/amenorrheic athletes experienced ROM with nonpharmacologic therapy.
      Mean time to ROM among all athletes with menstrual disturbances was 15.6 +/- 2.6
      mo. Total absolute (5.3 +/- 1.1 kg vs. 1.3 +/- 1.1 kg, p < .05) and percentage
      (9.3% +/- 1.9% vs. 2.3% +/- 1.9%, p < .05) weight gain and increase in body-mass
      index (BMI; 1.9 +/- 0.4 kg/m2 vs. 0.5 +/- 0.4 kg/m2, p < .05) emerged as the
      primary differentiating characteristics between athletes with ROM and those
      without ROM. Percent weight gain was identified as a significant positive
      predictor of ROM, OR (95% CI) = 1.25 (1.01, 1.56), p < .05. CONCLUSIONS:
      Nonpharmacologic intervention in college athletes with menstrual disturbances can
      restore regular menstrual cycles, although ROM may take more than 1 yr. Weight
      gain or an increase in BMI may be important predictors of ROM.

PMID- 22465871
TI  - Load independence of two-dimensional speckle-tracking-derived left ventricular
      twist and apex-to-base rotation delay in nonischemic dilated cardiomyopathy:
      implications for left ventricular dyssynchrony assessment.
AB  - BACKGROUND: Left ventricular (LV) twist mechanics are a promising, sensitive tool
      for assessing pathophysiologic changes in patients with systolic heart failure.
      Although LV twist is known to be load dependent in healthy volunteers, this has
      not been examined in patients with "long-standing" dilated cardiomyopathy (DCM).
      The aim of this study was to determine whether LV twist remains load dependent in
      the setting of long-standing, nonischemic DCM. METHODS: Thirty-four patients with
      DCM with baseline LV ejection fractions (LVEFs) < 40% and 13 subjects with
      preserved LVEFs (>=50%) were enrolled. After baseline measurements, pneumatic
      compression of the lower extremities (Pcom) was used to increase LV afterload.
      Subsequently, sublingual nitroglycerin (SL-NG) was administered to modify
      preload. Conventional echocardiographic parameters, LV end-systolic wall stress,
      net LV twist angle, and apex-to-base-rotation delay (ABRD) were assessed under
      each condition. RESULTS: In patients with DCM, although LV end-systolic wall
      stress significantly increased under Pcom (196.9 +/- 64.9 g/m(2) at baseline vs
      231.8 +/- 78.9 g/m(2) under Pcom, P < .017) and decreased after SL-NG application
      (231.8 +/- 78.9 g/m(2) under Pcom vs 197.4 +/- 67.4 g/m(2) after SL-NG, P <
      .017), net LV twist angle and ABRD showed no significant changes depending on LV
      loading condition (for LV twist, 7.63 +/- 4.47 degrees  at baseline vs 7.03 +/-
      4.13 degrees  under Pcom vs 7.35 +/- 4.36 degrees  after SL-NG, P = 0.65; for
      ABRD, 16.56 +/- 13.81% at baseline vs 17.19 +/- 14.81% under Pcom vs 15.95 +/-
      13.27% after SL-NG, P = .53). Careful examination of individual patient data
      revealed that LV twist was load independent when patients had LV twist < 12
      degrees . ABRD was also found to be load independent, but only in patients with
      LVEFs < 34%. In contrast, LV twist and ABRD were load dependent in patients with
      preserved LVEFs. CONCLUSIONS: LV twist and its component, ABRD, had relatively
      load insensitive properties in patients with long-standing DCM and can be used in
      future clinical trials as load-independent indexes of LV dyssynchrony.

PMID- 22465872
TI  - Noninvasive estimation of left ventricular compliance using three-dimensional
      echocardiography.
AB  - BACKGROUND: Left ventricular (LV) compliance is an important determinant of LV
      function and can be affected by a variety of cardiovascular conditions. In
      particular, diastolic dysfunction is associated with altered LV compliance.
      However, the evaluation of LV compliance is complex. Although the end-diastolic
      pressure-volume relationship (EDPVR) allows a direct, accurate evaluation of LV
      compliance, it requires invasive measurements. The aim of this study was to test
      the feasibility of noninvasive estimation of the EDPVR as a tool to evaluate LV
      compliance using three-dimensional echocardiography. METHODS: Sixty-eight
      subjects were studied, including 23 normal controls, 22 patients with increased
      LV compliance due to dilated cardiomyopathy, and 23 patients with reduced LV
      compliance secondary to isolated diastolic dysfunction as defined using current
      American Society of Echocardiography guidelines. The EDPVR was calculated for
      each subject using a nonlinear model with echocardiographic estimates of end
      diastolic pressure and volume. For both the isolated diastolic dysfunction and
      dilated cardiomyopathy groups, predicted end-diastolic volumes at predetermined
      pressure values (5, 10, 20, and 30 mm Hg) were compared with values in normal
      controls. RESULTS: Compared with controls, noninvasive estimates of the EDPVR
      resulted in predicted end-diastolic volumes that were lower in the isolated
      diastolic dysfunction group and higher in the dilated cardiomyopathy group (P <
      .0001 for all four pressure levels). In addition, a stepwise trend of decreased
      compliance was noted for the different grades of diastolic dysfunction.
      CONCLUSIONS: This is the first study to demonstrate the feasibility of
      noninvasive estimation of the LV EDPVR and its ability to differentiate normal
      from abnormal LV compliance using three-dimensional echocardiography.

PMID- 22465873
TI  - Pre-diagnostic acrylamide exposure and survival after breast cancer among
      postmenopausal Danish women.
AB  - Acrylamide is a probable human carcinogen, with industrial contact, tobacco
      smoking and foods processed at high temperatures as the main routes of exposure.
      In animal studies oral intake of acrylamide has been related to cancer
      development, with indications that the increased cancer occurrence especially
      regards endocrine related tumors. In human epidemiological studies, dietary
      exposure to acrylamide has also been suggested related to higher risk of
      endocrine related tumors, like estrogen sensitive breast cancer. The aim of the
      present study was to evaluate if pre-diagnostic acrylamide exposure, measured by
      acrylamide and glycidamide hemoglobin adducts (AA-Hb and GA-Hb), were associated
      to mortality in breast cancer cases. Among 24,697 postmenopausal women included
      into a Danish cohort between 1993 and 1997, 420 developed breast cancer before
      2001 and 110 died before 2009. AA-Hb and GA-Hb concentrations measured in blood
      samples were related to mortality by Cox proportional hazard models. Estimates
      are given per 25 pmol/g globin higher levels. Among non-smokers, higher
      concentrations of GA-Hb were associated to a higher hazard rate of breast cancer
      specific mortality (HR (95% CI): 1.63 (1.06-2.51)), the hazard rate among women
      diagnosed with estrogen receptor positive tumors was (HR (95% CI): 2.23 (1.38
      3.61)). For AA-Hb the tendency was similar, but only statistically significant
      among those with estrogen receptor positive tumors (HR (95% CI): 1.31 (1.02
      1.69)). In conclusion, the present study indicates that pre-diagnostic exposure
      to acrylamide may be related to mortality among breast cancer patients and that
      this may especially concern the most endocrine related type of breast cancer.

PMID- 22465874
TI  - Biochemistry and semiconductor electronics--the next big hit for silicon?
AB  - Two recent developments portend a new era for silicon electronics in biomedical
      applications. Firstly, highly specific chemical recognition and massively
      parallel sample preparation techniques are being combined with VLSI to make new
      kinds of analytical chips. Secondly, critical dimensions are beginning to
      approach the size of biomolecules, opening new pathways for physical interactions
      between molecules and semiconductor structures. Future generations of hybrid
      chemical-CMOS devices could revolutionize diagnosis and make personalized
      medicine cheap enough to become widespread.

PMID- 22465875
TI  - Quantification of residual dentine thickness following crown preparation.
AB  - OBJECTIVES: Pulpal response to tooth preparation is a major concern in fixed
      prosthodontics. Research has suggested that 2mm or more of remaining dentine is
      critical in protecting the pulp following tooth preparation. However, clinicians
      have no means of knowing dentine thickness either before or after preparation and
      therefore lack feedback about this important aspect of preparation quality. The
      aim of this project was to develop a method for measuring local dentine thickness
      following tooth preparation for metal ceramic crowns, in vitro, which could be
      used as a tool to evaluate preparation technique and instrumentation. METHODS:
      Microtomography (XMT or micro-CT) scans were taken of extracted teeth before and
      after crown preparation. Local dentine thickness was defined for every voxel
      within the 3D tooth image as the sum of distances from that voxel to the pulp and
      to the anatomical surface. The method also allows the thickness of material
      removed to be quantified. Three-dimensional colour-coded maps of dentine
      thickness were generated, and the distributions of dentine thickness throughout
      the teeth were analysed. This was tested by a single operator on sixteen
      extracted upper central incisors. RESULTS: This method enabled clear
      visualisation and analysis of residual dentine thickness. In the trial, it
      revealed consistent over-prepared regions along the labial proximal line angles
      which, in a clinical case, could affect subsequent tooth and restoration
      longevity. All but one of the prepared teeth had regions with a residual dentine
      thickness of less than 1.5mm, in 6 it was less than 1.0mm and in 3 of these it
      was less than 0.5mm. CONCLUSION: Although ex vivo, this method can be used as a
      research tool to look for patterns of over- or under-preparation, leading to
      possible modification of technique, instrumentation and, or crown design.
      CLINICAL SIGNIFICANCE: It is not currently possible for clinicians to know the
      thickness of residual dentine following crown preparation, a key factor in long
      term outcome. The described method of quantifying and visualising this thickness
      allows preparation techniques and instrumentation to be evaluated in vitro,
      leading to prospective improvements in clinical procedures.

PMID- 22465876
TI  - Degree of conversion and microhardness of TPO-containing resin-based composites
      cured by polywave and monowave LED units.
AB  - OBJECTIVES: To determine the degree of conversion (DC) and Knoop microhardness
      (KHN) of resin-based composites (RBCs) containing trimethylbenzoyl
      diphenylphosphine oxide (TPO) cured by polywave or monowave LED light-curing
      units (LCUs). METHODS: Three groups (each n = 5) of Tetric EvoCeram (Ivoclar
      Vivadent), Vit-l-escence (Ultradent) and Herculite XRV Ultra (Kerr) were prepared
      in Teflon moulds (5mm in diameter and 2mm thick) and cured with polywave
      Bluephase((r)) G2 (Ivoclar Vivadent), polywave Valo (Ultradent) or monowave
      Bluephase((r)) (Ivoclar Vivadent; control) resulting in 9 groups. DC and KHN were
      determined using micro-Raman spectroscopy and Knoop microhardness, respectively.
      High-performance liquid chromatography and nuclear magnetic resonance
      spectroscopy were used to confirm the presence or absence of TPO in the three
      uncured materials. Data were statistically analysed using two-way and one-way
      ANOVA and DC and KHN were correlated using Pearson's correlation (alpha = 0.05).
      RESULTS: TPO was confirmed in Tetric EvoCeram and Vit-l-escence but not in
      Herculite XRV Ultra. All three LCUs produced comparable KHN for Tetric EvoCeram
      and Herculite XRV Ultra (p > 0.05). Both polywave LCUs resulted in significantly
      higher KHN for Vit-l-escence and higher DC in Tetric EvoCeram and Vit-l-escence
      than the monowave Bluephase((r)) (p < 0.05). Conversely, Bluephase((r)) showed
      higher DC than the two polywave LCUs in Herculite XRV Ultra (p < 0.05). Pearson's
      correlation coefficient was r = 0.818. CONCLUSIONS: Polywave LED LCUs improved
      monomer to polymer conversion and KHN in the two TPO-containing RBCs, but not in
      Herculite XRV Ultra. DC and KHN were linearly correlated in all three RBCs. Vit-l
      escence showed the highest DC and KHN of the three materials tested. CLINICAL
      SIGNIFICANCE: The use of polywave LEDs significantly improves both the DC and KHN
      of materials which contain TPO. This should be taken into account when curing
      bleached shades of RBCs even if the manufacturers do not indicate the presence of
      TPO in their materials.

PMID- 22465877
TI  - Should religious beliefs be allowed to stonewall a secular approach to
      withdrawing and withholding treatment in children?
AB  - Religion is an important element of end-of-life care on the paediatric intensive
      care unit with religious belief providing support for many families and for some
      staff. However, religious claims used by families to challenge cessation of
      aggressive therapies considered futile and burdensome by a wide range of medical
      and lay people can cause considerable problems and be very difficult to resolve.
      While it is vital to support families in such difficult times, we are
      increasingly concerned that deeply held belief in religion can lead to children
      being potentially subjected to burdensome care in expectation of 'miraculous'
      intervention. We reviewed cases involving end-of-life decisions over a 3-year
      period. In 186 of 203 cases in which withdrawal or limitation of invasive therapy
      was recommended, agreement was achieved. However, in the 17 remaining cases
      extended discussions with medical teams and local support mechanisms did not lead
      to resolution. Of these cases, 11 (65%) involved explicit religious claims that
      intensive care should not be stopped due to expectation of divine intervention
      and complete cure together with conviction that overly pessimistic medical
      predictions were wrong. The distribution of the religions included Protestant,
      Muslim, Jewish and Roman Catholic groups. Five of the 11 cases were resolved
      after meeting religious community leaders; one child had intensive care withdrawn
      following a High Court order, and in the remaining five, all Christian, no
      resolution was possible due to expressed expectations that a 'miracle' would
      happen. 

PMID- 22465879
TI  - Mammary cancer promotion by ovarian hormones involves IGFR/AKT/mTOR signaling.
AB  - In a previous study, we observed that N-methyl-N-nitrosourea (MNU)-induced
      mammary lesions are promoted to overt mammary cancers by exogenous administration
      of estradiol (E) and progesterone (P). The purpose of the present study was to
      identify the early molecular events occurring during the hormonal promotion of
      mammary carcinogenesis and persistent activation of molecular pathways
      responsible for tumor growth. Seven-week-old female Copenhagen (COP) rats, which
      are resistant to MNU-induced mammary carcinogenesis, were intraperitoneally
      administered a single dose of MNU (50 mg/kg body weight). Six weeks after
      carcinogen administration, the rats were treated with E+P, killed at 15th week
      and 43rd week to obtain mammary lesions and tumor tissues and the molecular
      analysis were performed. Quantitative RT-PCR experiments showed increased mRNA
      expression of Igfr, Grb2, Sos1, and Shc1 in mammary lesions and tumors.
      Immunoblot data also showed increased protein levels of IGFR, GRB2 and SHC1 in
      mammary lesions and tumors, which is in correlation with their respective RT-PCR
      data. Activation of AKT and ERK1/2 were up regulated in E+P treated mammary
      lesions and tumors. Molecular analysis of mTOR pathway proteins revealed
      increased phosphorylation of p70S6K and 4EBP1 in the hormone treated tumors
      indicating the activation of mTOR signaling. E+P treatment reduced the protein
      expression of BAX and increased BCL2 expression along with down regulation of
      active caspase 3 and 8. Together, these data demonstrate that ovarian hormones
      promote the lesions to mammary tumors by enhancing IGFR and Akt/mTOR signaling
      along with inhibition of apoptotic stimuli.

PMID- 22465880
TI  - DAPk1 inhibits NF-kappaB activation through TNF-alpha and INF-gamma-induced
      apoptosis.
AB  - Recent studies have shown DAPk as a molecular modulator induced by the second
      messenger, responsible for controlling cell destiny decisions, but the detailed
      mechanism mediating the role of DAPk1 during cell death is still not fully
      understood. In this present report, we attempted to characterize the effects of
      TNF-alpha and INF-gamma on DAPk1 in human ovarian carcinoma cell lines, OVCAR-3.
      Both TNF-alpha and INF-gamma significantly induce DAPk1 levels in a time
      dependent manner. At the same time, they both arrested cell cycle progression in
      the G(0)-G(1) and G2/M phase, down-regulated cyclin D1, CDK4 and NF-kappaB
      expression, while also up-regulating p27 and p16 expression. Subsequently, the
      efficacy of the combined treatment with DAPk1 was investigated. In the presence
      of DAPk1, TNF-alpha or INF-gamma-induced apoptosis was additively increased,
      while TNF-alpha or INF-gamma-induced NF-kappaB activity was inhibited.
      Conversely, TNF-alpha or INF-gamma-dependent NF-kappaB activity was further
      enhanced by the inhibition of DAPk1 with its specific siRNA. The activity of NF
      kappaB was dependent on the level of DAPk1, indicating the requirement of DAPk1
      for the activation of NF-kappaB. Low levels of DAPk1 expression were frequently
      observed in different human patient's tissue and cancer cell lines compared to
      normal samples. In addition, over-expression of DAPk1 from either TNF-alpha or
      INF-gamma-treatment cells suppressed the anti-apoptosis protein XIAP as well as
      COX-2 and ICAM-1, more than control. Taken together, our data findings suggest
      that DAPk1 can mediate the pro-apoptotic activity of TNF-alpha and INF-gamma via
      the NF-kappaB signaling pathways.

PMID- 22465881
TI  - Subjective fear, interference by threat, and fear associations independently
      predict fear-related behavior in children.
AB  - BACKGROUND AND OBJECTIVES: Several information-processing models highlight the
      independent roles of controlled and automatic processes in explaining fearful
      behavior. Therefore, we investigated whether direct measures of controlled
      processes and indirect measures of automatic processes predict unique variance
      components of children's spider fear-related behavior. METHOD: Seventy-seven
      children between 8 and 13 years performed an Affective Priming Task (APT)
      measuring associative bias, a pictorial version of the Emotional Stroop Task
      (EST) measuring attentional bias, filled out the Spider Anxiety and Disgust
      Screening for Children (SADS-C) in order to assess self-perceived fear, and took
      part in a Behavioral Assessment Test (BAT) to measure avoidance of spiders.
      RESULTS: The SADS-C, EST, and APT did not correlate with each other. Spider fear
      related behavior was best explained by SADS-C, APT, and EST together; they
      explained 51% of the variance in BAT behavior. LIMITATIONS: No children with
      clinical levels of spider phobia were tested. The direct and the different
      indirect measures did no correlate with each other. CONCLUSIONS: These results
      indicate that both direct and indirect measures are useful for predicting unique
      variance components of fear-related behavior in children. The lack of relations
      between direct and indirect measures may explain why some earlier studies did not
      find stronger color-naming interference or stronger fear associations in children
      with high levels of self-reported fear. It also suggests that children with high
      levels of spider-fearful behavior have different fear-related associations and
      display higher interference by spider stimuli than children with non-fearful
      behavior.

PMID- 22465882
TI  - Actions of incretin metabolites on locomotor activity, cognitive function and in
      vivo hippocampal synaptic plasticity in high fat fed mice.
AB  - The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) improve markers of cognitive function in obesity
      diabetes, however, both are rapidly degraded to their major metabolites, GLP-1(9
      36)amide and GIP(3-42), respectively. Therefore, the present study investigated
      effects of GLP-1(9-36)amide and GIP(3-42) on locomotor activity, cognitive
      function and hippocampal synaptic plasticity in mice with diet-induced obesity
      and insulin resistance. High-fat fed Swiss TO mice treated with GLP-1(9-36)amide,
      GIP(3-42) or exendin(9-39)amide (twice-daily for 60 days) did not exhibit any
      changes in bodyweight, non-fasting plasma glucose and plasma insulin
      concentrations or glucose tolerance compared with high-fat saline controls.
      Similarly, locomotor and feeding activity, O(2) consumption, CO(2) production,
      respiratory exchange ratio and energy expenditure were not altered by chronic
      treatment with incretin metabolites. Administration of the truncated metabolites
      did not alter general behavior in an open field test or learning and memory
      ability as recorded during an object recognition test. High-fat mice exhibited a
      significant impairment in hippocampal long-term potentiation (LTP) which was not
      affected by treatment with incretin metabolites. These data indicate that
      incretin metabolites do not influence locomotor activity, cognitive function and
      hippocampal synaptic plasticity when administered at pharmacological doses to
      mice fed a high-fat diet.

PMID- 22465883
TI  - Timing of long bone fracture fixation in severe traumatic brain injury.
AB  - We present a review of the published evidence on the optimal timing for long bone
      fracture fixation in severe traumatic brain injury (TBI); a matter that remains
      under debate. Fifteen retrospective articles (level II-3 evidence) were
      considered suitable for the review. We conclude that the published evidence does
      not provide a definitive answer to the optimal timing of long bone fracture
      surgery in severe TBI, and a randomized controlled trial is required. We
      recommend a safe strategy that combines damage control surgery with a period of
      monitoring of intracranial pressure, cerebral perfusion pressure, and if
      available brain tissue oxygen until the patient is considered fit for the
      fracture fixation.

PMID- 22465884
TI  - Management of women with epilepsy. Practical issues faced when dealing with women
      with epilepsy.
AB  - Epilepsy is commonly encountered in neurology practice, affecting more than 50
      million people worldwide, according to the World Health Organization reports.
      Management of women with epilepsy requires attention to some considerations
      including the hormonal changes and its impact on epilepsy, the interaction
      between oral contraceptives and antiepileptic drugs (AEDs), pregnancy, and the
      potential teratogenic risk associated with AEDs use during that period.
      Similarly, the effect of AEDs on bone health should always be considered, and
      measures should be taken to reduce the risk of osteoporosis given the fact that
      women in their menopause are at increased risk. Despite the considerable risk of
      teratogenicity with AEDs use in pregnancy, more than 90% of pregnancies will be
      uneventful.

PMID- 22465878
TI  - Estrogen receptor-beta and breast cancer: translating biology into clinical
      practice.
AB  - Estrogen receptor (ER) beta was discovered over a decade ago. The design of most
      studies on this receptor was based on knowledge of its predecessor, ERalpha.
      Although breast cancer (BCa) has been a main focus of ERbeta research, its
      precise roles in breast carcinogenesis remain elusive. Data from in vitro models
      have not always matched those from observational or clinical studies. Several
      inherent factors may contribute to these discrepancies: (a) several ERbeta
      spliced variants are expressed at the protein level, and isoform-specific
      antibodies are unavailable for some variants; (b) post-translational
      modifications of the receptor regulate receptor functions; (c) the role of the
      receptor differs significantly depending on the type of ligands, cis-elements,
      and co-regulators that interact with the receptor; and (d) the diversity of
      distribution of the receptor among intracellular organelles of BCa cells. This
      review addresses the gaps in knowledge in ERbeta research as it pertains to BCa
      regarding the following questions: (1) is ERbeta a tumor suppressor in BCa?; (2)
      do ERbeta isoforms play differential roles in breast carcinogenesis?; (3) do
      nuclear signaling and extranuclear ERbeta signaling differ in BCa?; (4) what are
      the consequences of post-translational modifications of ERbeta in BCa?; (5) how
      do co-regulators and interacting proteins increase functional diversity of
      ERbeta?; and (6) how do the types of ligand and regulatory cis-elements affect
      the action of ERbeta in BCa?. Insights gained from these key questions in ERbeta
      research should help in prevention, diagnosis/prognosis, and treatment of BCa.

PMID- 22465885
TI  - An evaluation of the effectiveness of pre-ischemic hyperbaric oxygen and post
      ischemic aminoguanidine in experimental cerebral ischemia.
AB  - OBJECTIVE: To study the effects of pre-ischemic hyperbaric oxygen (HBO) and post
      ischemic aminoguanidine (AG) on the infarct volume in permanent middle cerebral
      artery occlusion. METHODS: This study was approved by the Animal Experiments
      Ethics Committee of Gulhane Military Medical Academy, Ankara, Turkey and carried
      out from March 2006 to August 2006. A total of 28 Sprague-Dawley rats (200-320 g)
      were divided into 4 groups: control (K) group (n = 7); HBO group (n = 7); HBO +
      AG group (n = 7); and the  AG group (n = 7). All rats underwent middle cerebral
      artery occlusion (MCAO) by subtemporal craniectomy, and permanent ischemia was
      created. A 2.8 atmospheric pressure of HBO was first applied to the HBO and HBO +
      AG groups for 45 minutes, and occlusion was created after 2 hours. In the HBO +
      AG group, intraperitoneal administration of AG hemisulfate (100 mg/kg) was
      started 6 hours after MCAO, and was continued twice a day for 3 days. RESULTS:
      The rate of infarction was found to be 22.2+/-3.1% in the control group, 16.1+/
      2.7% in the HBO group, 15.2+/-1.9% in the HBO+AG group, and 14.4+/-3.3% in the AG
      groups. The rate of infarctions (therefore the volume of infarct) in the HBO, HBO
      + AG, and AG groups were found to be significantly decreased compared with the
      control group (p=0.002, p=0.001, and p=0.001). CONCLUSION: In permanent MCAO
      induced ischemia in rats, HBO and AG were observed to have a lowering effect on
      the infarct volume, but no additive effect was observed. This situation can be
      explained by different mechanisms of action.

PMID- 22465886
TI  - Endovascular treatment of an intracranial aneurysm with a ruptured bleb.
AB  - OBJECTIVE: To study the features and approaches of endovascular treatment for
      intracranial aneurysms with a ruptured bleb. METHODS: This retrospective study
      was carried out from June 2007 to June 2009 in Jilin University, Jilin, China.
      Thirty patients with intracranial aneurysms with ruptured blebs were included.
      The aneurysms were diagnosed by digital subtraction angiography (DSA), and the
      endovascular treatment was planned according to the relationship between the
      aneurysm body and the ruptured bleb. The aneurysms were classified into 4 types
      (type I, II, III, IV) based on the size of the neck of the aneurysm connected
      with the parent artery, the size of the body of the aneurysm, and the size of the
      junction formed between the aneurysm and bleb. Endovascular treatment for each
      type of aneurysm was performed. RESULTS: Type IV aneurysms were the most
      difficult operation performed, easily resulting in rupture and bleeding during
      surgery, whereas embolization of a type III aneurysm was relatively simple. Type
      I and II aneurysms resulted in better prognosis. Statistical analysis showed that
      the outcome of the treatment of type I and II aneurysms was better than that in
      type III and IV aneurysms, the outcome of type I, II, and III was better than
      that in type IV. CONCLUSION: The outcome of the endovascular treatment of an
      intracranial aneurysm with a ruptured bleb was related to the aneurysm type.
      Treatment in a type-dependent manner is therefore recommended.

PMID- 22465887
TI  - Endovascular treatment of ruptured peripheral intracranial aneurysms.
AB  - OBJECTIVE: To assess the feasibility and result of endovascular treatments for
      ruptured peripheral intracranial aneurysms. METHODS: We retrospectively reviewed
      our experience and results of endovascular treatments for a series of 18
      consecutive patients with ruptured distal intracranial aneurysms at the
      Department of Neurosurgery, Southwest Hospital, Chongqing, China between January
      2005 and June 2010. Depending on the location and shape of the aneurysms, we used
      various therapeutic strategies including selective aneurysmal coiling, parent
      artery (and aneurysm) occlusion, stent-assisted coiling, and microcatheter
      assisted coiling. RESULTS: Endovascular embolization was technically successful
      in all patients. Five patients were treated by selective aneurysm coiling; 5
      patients were embolized with the stent-assisted technique or microcatheter
      assisted technique. In the remaining 8 patients, the parent arteries, or together
      with the aneurysms were occluded using coils or glue. No procedure complication
      such as thrombosis or aneurysmal rupture was encountered during treatment. Two
      patients treated with parent artery occlusion developed acute or delayed
      transient ischemic symptoms, but they eventually made a good recovery. No patient
      has experienced postprocedural hemorrhage during the follow-up period (5-66
      months; mean, 22.2 months). CONCLUSION: Endovascular treatment is a feasible and
      effective therapeutic alternative for peripheral intracranial aneurysms.

PMID- 22465888
TI  - Adaptation of the dizziness handicap inventory for use in the Arab population.
AB  - OBJECTIVE: To generate an Arabic version of the Dizziness Handicap Inventory
      (DHI), and to assess its reliability by applying it to a group of patients with
      vestibular disorders and control healthy subjects of Arabic origin. METHODS: The
      Arabic version of the DHI was developed using the standard protocol for test
      translation. This pilot study was carried out between January 2009 and January
      2011 at the Otology/Neurotology Clinic at King Abdulaziz University Hospital,
      Riyadh, Kingdom of Saudi Arabia. The translated version was then tested using 50
      patients with vestibular disorders, and 50 control subjects. Participants'
      responses were statistically analyzed for internal consistency within and between
      the patient and control groups. RESULTS: An Arabic DHI showed a significantly
      high internal consistency and reliability. Cronbach's alpha coefficient with 95%
      confidence interval for functional score among patients was 0.87 (0.81-0.92),
      0.81 (0.72-0.88) for physical score, 0.79 (0.69-0.87) for emotional score, and
      0.92 (0.89-0.95) for the overall DHI score. A significant difference was found in
      domain scores and total DHI score between the dizzy and control groups (p=0.00).
      CONCLUSION: The Arabic version of the DHI is a valid and reliable self-assessment
      tool for the severity of vestibular disorders.

PMID- 22465889
TI  - Anxiety and depression among traumatic spinal cord injured patients.
AB  - OBJECTIVE: To investigate the relation between gender, sociodemographic factors,
      pain, smoking, and the level of anxiety and depressive symptoms after traumatic
      spinal cord injury (TSCI) in a Saudi sample. METHODS: We conducted a cross
      sectional study from November 2009 to April 2011, in 102 (age range 17-70 years;
      84 males, 18 females) TSCI patients admitted to the Spinal Cord Injury Unit,
      Sultan Bin Abdulaziz Humanitarian City, Riyadh, Saudi Arabia. We used the
      Hospital Anxiety and Depression Scale (HADS) to measure the level of anxiety and
      depression of the study population. The demographic variables were recorded.
      RESULTS: Compared to male TSCI patients, the level of anxiety (p=0.0001),
      depression (p=0.0045), and total HADS (p=0.0002) scores were significantly higher
      in females. The correlation between level of education and anxiety and depression
      showed that patients with a university education had higher anxiety (p=0.0115),
      depression (p=0.0437), and total HADS (p=0.0272) than patients with a lower
      education level. The TSCI patients with pain reported more anxiety and depression
      than patients who did not have pain. Compared to non-smokers, the smokers showed
      marked but insignificant higher levels of anxiety and depression. CONCLUSION:
      Women with TSCI are at a significantly higher risk of having anxiety and
      depressive symptoms. Level of university education was modestly correlated with
      higher level anxiety and depression in this population.

PMID- 22465891
TI  - Periodic catatonia. Challenging diagnosis for psychiatrists.
AB  - Periodic catatonia (PC) is a rare type of catatonia syndrome, in which the
      catatonic phases often repeat regularly. Between the catatonic periods, the
      symptoms totally disappear and make the diagnosis difficult. We report a case
      with PC who did not show any catatonic symptoms except anxiety and restlessness
      in his first referral to the hospital. Although it was reported that he showed
      the symptoms of the disorder such as mutism, and immobility, he was not
      hospitalized. In his next referral (24 hours later), he was referred with
      catatonic symptoms and was hospitalized. The periods of catatonia were repeated
      regularly before electroconvulsive therapy, so the primary diagnosis was PC.
      During treatment with ECT, based on the semi-structured interview, a diagnosis of
      bipolar mood disorder was made. Due to the disappearance of symptoms between
      catatonic periods, this disorder may be underestimated and treatment postponed.

PMID- 22465890
TI  - Erythropoietin for acute multiple sclerosis in patients with optic neuritis as a
      first demyelination event.
AB  - OBJECTIVE: To investigate the safety, tolerability, and short-term efficacy of
      treatment with erythropoietin in patients with optic neuritis as a first
      demyelination event. METHODS: We conducted this randomized double-blind pilot
      study in the Shiraz University of Medical Sciences, Shiraz, Iran, from March 2007
      to January 2009. The participants were patients aged 18-45 years with optic
      neuritis and at least 3 hyperintense lesions on T2-weighted and FLAIR MRI, but no
      clinically definite multiple sclerosis (MS). They were randomized into 2 groups.
      The case group (5 patients) received intravenous methyl prednisolone (1000 mg/24
      hours) and intravenous erythropoietin (20,000 unit/24 hours) for 5 consecutive
      days, and the control group (5 patients) received intravenous methyl prednisolone
      at the same dose as the case group, and a placebo. The groups were followed for
      one year and compared for adherence to protocol, adverse drug effects, mean
      duration of conversion to clinically definite MS, and MRI changes. RESULTS: All
      patients tolerated the protocol. One patient who received erythropoietin
      developed cerebral venous sinus thrombosis and anti-cardiolipin antibody
      positivity. One patient in the control group, but no patients in the case group,
      fulfilled the McDonald criteria for MS during the follow-up period, but none of
      the participants in either group developed clinically definite MS according to
      the Poser criteria. CONCLUSION: Erythropoietin may be effective, but should be
      used with caution.

PMID- 22465892
TI  - Incomplete oculomotor nerve palsy in the subarachnoid space caused by traumatic
      brain injury.
AB  - A patient with traumatic brain injury showed incomplete oculomotor nerve palsy in
      the subarachnoid space. A 12-year-old girl was hospitalized after a head injury.
      Neuro-ophthalmic examination showed that the left eye had a ptosis and pupillary
      involvement. An MRI indicated an intracranial hematoma at the basilar portion of
      the left temple. The ptosis and pupillary involvement improved after elimination
      of the hematoma. The presentation patterns are best explained by topographic
      organization of the third nerve fiber within the subarachnoid space. This case
      suggests that the topographic organization of the third nerve should be
      considered in diagnosis of oculomotor nerve palsy.

PMID- 22465893
TI  - Ruptured giant middle cerebral artery aneurysm in infancy.
AB  - Intracranial aneurysms are uncommon in children. Rupture of giant intracranial
      aneurysms is extremely uncommon in infants even in autopsy studies. In this
      report, we present an unusual case of ruptured giant middle cerebral artery
      aneurysm in an 11-month-old female infant who presented acutely with
      unresponsiveness and seizures. The aneurysm was clipped during an urgent
      craniotomy for evacuation of an associated hematoma. She recovered slowly with
      mild residual right-sided weakness. Follow up arterial angiography revealed no
      residual or other aneurysms. Further follow up revealed motor delay and recurrent
      partial seizures. Active physiotherapy was performed and she could walk
      independently by 3 years of age. We conclude that intracranial aneurysms have to
      be considered in the differential diagnosis of infants presenting with acute
      raised intracranial pressure. Favorable outcome is noted in children who are
      managed promptly in hospitals with neurosurgical units.

PMID- 22465894
TI  - Ulnar neuropathy caused by traumatic arterio-venous fistula following gunshot
      wound.
AB  - This report concerns a case of a 32-year-old male with right ulnar neuropathy
      caused by arterio-venous fistula due to gunshot wound injury presenting with
      severe neuropathic pain along the ulnar nerve distribution. Intra-operative
      exploration and ligation of the fistula relieved the patient's neuropathic pain.
      A review of the recent English literature did not reveal any reports of arterio
      venous fistula of the ulnar nerve.

PMID- 22465895
TI  - Chronic inflammatory demyelinating polyneuropathy following malignant melanoma.
AB  - Polyneuropathy has rarely been encountered in association with melanoma. Although
      this association may be a biologically plausible phenomenon considering the
      common embryonic origin of the melanocytes and Schwann cells with proven antibody
      cross reactivity, only few such cases have been reported so far. We report 2 new
      cases of chronic inflammatory demyelinating polyneuropathy in association with
      malignant melanoma, which we believe will add more evidence of this association.
      We also include a short review of the literature for similar cases.

PMID- 22465896
TI  - Epidemiology of neuro-genetic disorders in Northwestern Iran.

PMID- 22465897
TI  - Cardiovascular autonomic dysfunction in type 2 diabetes mellitus and essential
      hypertension in a South Indian population.

PMID- 22465898
TI  - A lady with facio-linguo-pharyngeal-masticatory diplegia.

PMID- 22465899
TI  - Suggestions from the field for return to sports participation following anterior
      cruciate ligament reconstruction: basketball.
AB  - The purpose of this paper is to outline the final, functional phases of
      rehabilitation that address exercises, drills, and return-to-play criteria for
      the sport of basketball, following anterior cruciate ligament (ACL)
      reconstruction. ACL injuries can be debilitating and affect the quality of life
      for recreational and elite athletes alike. Tears of the ACL are common in both
      male and female basketball players, with a higher incidence rate in females.
      Incidence of a retear to the existing graft or contralateral knee within 5 years
      of ACL reconstruction with patellar tendon autograft in young (less than 18 to 25
      years of age), active basketball players can be as high as 52%. Reducing the
      number of ACL injuries or reinjury, of which there are an estimated 80 000 per
      year at an associated cost of over a billion dollars, can have significant
      potential long-term fiscal and health benefits. Following surgical reconstruction
      of the ACL, implementing a tailored rehabilitation protocol can ensure a
      successful return to sport. When searching the literature for such protocols,
      clinicians may struggle to find specific exercises, drills, and return-to-play
      criteria for particular sports. The intent of this manuscript is to present such
      a rehabilitation protocol for basketball.

PMID- 22465900
TI  - Haemozoin detection in infected erythrocytes for Plasmodium falciparum malaria
      diagnosis-prospects and limitations.
AB  - Several methods based on the detection of the parasite-specific pigment haemozoin
      (Hz) in blood are currently being investigated as alternative diagnostic methods
      for malaria. Although this approach may appear attractive, the fact that in
      Plasmodium falciparum (P. f.) malaria, the severity of which should give it the
      highest diagnostic priority, the fact that most circulating intra-erythrocytic P.
      f. parasites contain little or no Hz raises some concern. We used flow cytometry
      to investigate the possibilities and limitations of the detection of intra
      erythrocytic Hz in malaria infected patient blood samples and in vitro cultures.
      However, reliable detection of ring-forms or young trophozoites of P. f.
      parasites could not be achieved, although one-quarter of mature parasites could
      be detected after 24-48 h in culture. Our results strongly suggest that, although
      it may be useful for monitoring maturation, detection of intra-erythrocytic Hz by
      flow cytometry will not provide an optimal method for diagnosis of P. falciparum
      malaria.

PMID- 22465901
TI  - Influence of yeast-derived 1,3/1,6 glucopolysaccharide on circulating cytokines
      and chemokines with respect to upper respiratory tract infections.
AB  - OBJECTIVE: Wellmune WGP is a food supplement containing a refined 1,3/1,6
      glucopolysaccharide that improves the antimicrobial activity of the innate immune
      cells by the priming of lectin sites. This study aimed to investigate whether
      Wellmune decreases the frequency and severity of upper respiratory tract
      infection (URTI) symptoms over 90 d during the peak URTI season in healthy
      university students. The secondary aims included an assessment of plasma cytokine
      and chemokine levels. METHODS: This was a randomized, double-blinded, placebo
      controlled trial lasting 90 d. One hundred healthy individuals (18-65 y old, mean
      age ~21 y) were randomized to 250 mg of Wellmune once daily or to an identical
      rice flour-based placebo. Health was recorded daily and two or more reported URTI
      symptoms for 2 consecutive days triggered a medical assessment and blood
      collection within 24 h. The URTI symptom severity was monitored. Plasma cytokines
      and chemokines were measured at day 0, day 90, and during the confirmed URTI.
      RESULTS: Ninety-seven participants completed the trial (Wellmune, n = 48;
      placebo, n = 49). The Wellmune tended to decrease the total number of days with
      URTI symptoms (198 d, 4.6%, versus 241 d, 5.5% in the control group, P = 0.06).
      The ability to "breathe easily" was significantly improved in the Wellmune group;
      the other severity scores showed no significant difference. Cytokines and
      chemokines were not different between the groups at study entry or day 90, but
      monocyte chemotactic protein-1 was lower in the Wellmune group during the URTI.
      CONCLUSION: Wellmune may decrease the duration and severity of URTI. Larger
      studies are needed to demonstrate this.

PMID- 22465902
TI  - Changes in dietary habits and eating practices in adolescents living in urban
      South Africa: the birth to twenty cohort.
AB  - OBJECTIVE: To assess changes in the dietary habits and eating practices of a
      longitudinal cohort of adolescents over a 5-y period living in Soweto and
      Johannesburg. METHODS: An interviewer-assisted questionnaire was used to gather
      data on the dietary habits and eating practices across three environments: in the
      home, in the school, and in the community. Participants (n = 1451, 49.1% male,
      89% black, and 11% with mixed ancestry) 13, 15, and 17 y old with complete data
      were included in the analyses. RESULTS: The weekday breakfast consumption
      decreased over the 5-y period, from 76% to 65% (P < 0.001); participants consumed
      breakfast during the weekend more regularly but this also decreased with age.
      Snacking while watching television increased with age, from 3.6 +/- 4.6 to 6.7 +/
      5.9 snacks/week, with female subjects consistently consuming more snacks than
      male subjects (P < 0.01). Two-thirds of participants ate their main meal with
      their families on most days at all three ages. Fast-food consumption increased by
      half a portion/week over the 5 y and confectionery consumption stayed the same,
      around 9 items/week in male subjects and 10 items/week in female subjects (P <
      0.02). Lunch box usage decreased with age; conversely, the number of tuck shop
      purchases increased. CONCLUSION: Poor eating habits in all three environments
      were found; the participants' propensity for foods that were energy dense and
      micronutrient poor was high. This study also found that dietary patterns are well
      established by 13 y of age.

PMID- 22465903
TI  - cis-9, trans-11, trans-13-Conjugated linolenic acid induces apoptosis and
      sustained ERK phosphorylation in 3T3-L1 preadipocytes.
AB  - OBJECTIVE: The aim of this study was to investigate the adipogenic effect of cis
      9, trans-11, trans-13-conjugated linolenic acid (c9,t11,t13-CLN), a fatty acid
      naturally present in bitter melon. METHODS: The 3T3-L1 murine preadipocyte cell
      line was used to test the effect of saponifiables from whole bitter melon and of
      commercially prepared pure c9,t11,t13-CLN on adipocyte differentiation. The
      effect of c9,t11,t13-CLN on 3T3-L1 cell viability was also tested at
      proliferation, mitotic clonal expansion, and terminal differentiation stages.
      RESULTS: Compared to the free fatty acid control mixture, the proadipogenic
      effect on 3T3-L1 was less potent using saponifiables obtained from bitter melon.
      C9,t11,t13-CLN, unlike its non-conjugated counterpart linolenic acid (LN) or
      other common fatty acids such as oleic acid or linoleic acid, exerted no
      proadipogenic effect on 3T3-L1. In contrast to LN displaying no cytotoxic effect
      at a concentration <=100 MUM, c9,t11,t13-CLN caused a dose-dependent reduction in
      the viability of pre- and postconfluent preadipocytes associated with apoptosis.
      Sustained ERK/MAPK activation, accompanied by increased peroxisome proliferator
      activated receptor gamma phosphorylation, was seen in c9,t11,t13-CLN-treated
      cells at initiation of differentiation. CONCLUSION: C9,t11,t13-CLN is less
      adipogenic for 3T3-L1 cells than LN and this is partly due to its apoptotic
      effect on proliferating preadipocytes and to the sustained ERK phosphorylation
      seen during mitotic clonal expansion.

PMID- 22465904
TI  - Evaluation of oral zinc sulfate effect on obsessive-compulsive disorder: a
      randomized placebo-controlled clinical trial.
AB  - OBJECTIVE: Obsessive-compulsive disorder is a common neuropsychiatric condition.
      Although various pharmaceutical agents are available for the treatment of
      obsessive-compulsive disorder, psychiatrists often find that many patients cannot
      tolerate the side effects of these medications, the patients do not respond
      properly to the treatment, or the medications lose their effectiveness after a
      period of treatment. The augmentation with safe supplementation of medication,
      such as with trace elements, may be a solution to some of these problems.
      METHODS: This study was a prospective, double-blinded, 8-wk trial. Twelve
      patients were given fluoxetine (20 mg/d) plus zinc (440 mg/d) and 11 patients
      were given fluoxetine plus placebo for 8 wk. RESULTS: Both groups showed a
      decrease in the mean Yale-Brown Obsessive-Compulsive Scale score. Based on t
      tests, in weeks 2 and 8, patients treated with fluoxetine plus zinc had
      significantly lower scores than those treated with fluoxetine plus placebo.
      CONCLUSION: The results show that zinc, as adjuvant agent for obsessive
      compulsive disorder, produces improved outcomes.

PMID- 22465905
TI  - Intracerebroventricular O-n-octanoylated ghrelin and its splice variant-induced
      feeding is blocked by insulin, independent of obestatin or CRF receptor, in
      satiated rats.
AB  - OBJECTIVE: The purpose of this study was to investigate the impact of
      intracerebroventricular (ICV) injection of the two endogenous forms of acyl
      ghrelin, O-n-octanoylated ghrelin and des-Gln14-ghrelin, on feeding behavior, as
      well as their interactions with insulin, obestatin, and corticotropin-releasing
      factor receptor (CRF-R) antagonist in the forebrain to influence food intake.
      METHODS: We examined the food intake in conscious, freely fed rats, which were
      chronically implanted with ICV catheters. RESULTS: O-n-octanoylated ghrelin and
      des-Gln14-ghrelin (0.1 nmol/rat) were equally potent in stimulating food intake
      in freely fed rats, up to 8 h after ICV injection (P < 0.05). In contrast, ICV
      administration of insulin (8 mU/rat), obestatin (2 nmol/rat), and astressin (2
      nmol/rat), a specific CRF-R antagonist, did not modify feeding in freely fed
      rats. Furthermore, pretreatment with ICV insulin (P < 0.01), but not obestatin or
      astressin, at the abovementioned dose, blocked central acyl-ghrelin-induced
      hyperphagic effects. CONCLUSION: ICV O-n-octanoylated ghrelin and its splice
      variant, des-Gln14-ghrelin, are equally potent to elicit food intake in freely
      fed rats, while these feeding-stimulating effects are opposed by insulin, but
      independent of obestatin and endogenous CRF-R in the forebrain.

PMID- 22465906
TI  - Antithrombotic activity of argan oil: an in vivo experimental study.
AB  - OBJECTIVE: Argan oil has been shown to inhibit in vitro and ex vivo platelet
      aggregation without extending bleeding time. In this report, we examined in vivo
      the antithrombotic activity of argan oil in an experimental thrombosis model in
      mice: acute pulmonary thromboembolism and in vitro its effect in a coagulation
      assay. METHODS: Acute pulmonary thromboembolism was induced, after argan oil
      treatment, by an intravenous injection of a collagen and epinephrine mixture. The
      paralyzed and dead mice in each group were numbered and the percentage of
      protection against acute pulmonary thromboembolism was calculated. The histologic
      study was conducted in lung tissue to estimate the percentage of opened and
      occluded vessels by platelet thrombi. The coagulation assay was monitored in
      platelet-poor plasma from normal rats by measuring the clotting parameters
      (activated partial thromboplastin time, prothrombin time, and thrombin time) in
      the presence and absence of argan oil. RESULTS: Argan oil (1 mL/100 g/day),
      administered orally, showed an antithrombotic activity preventing the paralysis
      or death (50%) induced by the collagen-epinephrine intravenous injection. This
      observation was confirmed by the lung histologic examination, in which the
      density of occluded blood vessels was significantly decreased (62.16 +/- 3.95%).
      However, the argan oil remained inactive for the coagulation parameters of
      activated partial thromboplastin time, prothrombin time, and thrombin time at
      variance with heparin, an anticoagulant reference drug. The antithrombotic
      activity of argan oil seemed unrelated to the anticoagulant activity. CONCLUSION:
      We suggest that argan oil might be an interesting natural dietary source for the
      nutritional prevention of hemostasis and cardiovascular disorders. Clinical
      trials would be necessary and relevant to confirm this hypothesis.

PMID- 22465907
TI  - Bioelectrical impedance phase angle as a prognostic marker in chronic heart
      failure.
AB  - OBJECTIVE: The main purpose of the present study was to assess the prognostic
      value of the bioelectrical phase angle (PA) in patients with heart failure
      independently of other parameters of a poor prognosis. METHODS: This
      retrospective study included 389 patients with heart failure. Anthropometric,
      body composition, clinical, biochemical, and echocardiographic data were
      collected from all patients. The quartiles were obtained for the PA, and patients
      were classified according to the quartiles into four groups. The endpoint was all
      cause mortality. A Cox proportional hazards regression analysis was performed to
      estimate the adjusted relative risks, and 95% confidence intervals were obtained
      for the potential predictors of death. RESULTS: Patients below the lowest
      quartile of PA (<4.2 degrees ) had decreased mean body mass index, handgrip
      strength, and hemoglobin values and a larger proportion of patients in New York
      Heart Association functional class III and renal failure. The Kaplan-Meier
      survival analysis among PA groups showed a better survival for patients above the
      highest quartile of PA (>=5.7 degrees ), and survival decreased as the PA
      decreased. The Cox regression analysis found that a PA <4.2 was an independent
      predictor of mortality (relative risk 3.08, 95% confidence interval 1.06-8.99),
      adjusting for age, hemoglobin levels, and diabetes, compared with a PA >=5.7.
      CONCLUSION: In this study population, a smaller PA was associated with
      malnutrition markers such as decreased body mass index, handgrip strength, and
      hemoglobin values and with a poor New York Heart Association functional class and
      renal failure. Adjusting for age, hemoglobin levels, and diabetes, a PA <4.2 was
      found to be an independent predictor of all-cause mortality in chronic heart
      failure.

PMID- 22465908
TI  - Comparison of poractant alfa and lyophilized lucinactant in a preterm lamb model
      of acute respiratory distress.
AB  - INTRODUCTION: A lyophilized formulation of lucinactant has been developed to
      simplify preparation and dosing. Endotracheal administration of surfactant can be
      associated with potentially harmful transient hemodynamic changes including
      decreases in cerebral blood flow and delivery of O2 to the brain. Efficacy and
      peri-dosing effects of poractant alfa and a lyophilized form of lucinactant were
      compared in this study. METHODS: Premature lambs (126-129 d gestation) were
      delivered by c-section, tracheostomized, ventilated, and instrumented with
      cerebral laser Doppler flowmetry and tissue PO2 probes. Pulmonary compliance and
      tidal volumes were monitored continuously and surfactant lung distribution was
      assessed. Lambs received either poractant alfa or lyophilized lucinactant and
      were monitored for 3 h after treatment. RESULTS: Both groups showed significant
      improvements in arterial pCO2, pH, pulmonary compliance, and tidal volume (all P
      < 0.01), a similar intra-pulmonary distribution profile, and no significant
      changes in arterial blood pressure or cerebral blood flow. Administration of
      poractant alfa was associated with higher mean airway pressures from 75 min post
      dosing and transiently decreased heart rate and increased brain tissue PO2 during
      the first 30 min after treatment. DISCUSSION: In this newborn lamb model of
      respiratory distress, lyophilized lucinactant results in improved lung function
      as compared with poractant alfa.

PMID- 22465909
TI  - Serum uric acid in U.S. adolescents: distribution and relationship to demographic
      characteristics and cardiovascular risk factors.
AB  - BACKGROUND: Despite being associated with multiple disease processes and
      cardiovascular outcomes, uric acid (UA) reference ranges for adolescents are
      lacking. We sought to describe the distribution of UA and its relationship to
      demographic, clinical, socioeconomic, and dietary factors among U.S. adolescents.
      METHODS: A nationally representative subsample of 1,912 adolescents aged 13-18
      years in NHANES 2005-2008 representing 19,888,299 adolescents was used for this
      study. Percentiles of the distribution of UA were estimated using quantile
      regression. Linear regression models examined the association of UA and
      demographic, socioeconomic, and dietary factors. RESULTS: Mean UA level was 5.14
      +/- 1.45 mg/dl. Mean UA increased with increasing age and was higher in non
      Hispanic white race, male sex, higher body mass index (BMI) Z-score, and with
      higher systolic blood pressure. In fully adjusted linear regression models, sex,
      age, race, and BMI were independent determinants of higher UA. CONCLUSIONS: This
      study defines serum UA reference ranges for adolescents. Also, it reveals some
      intriguing relationships between UA and demographic and clinical characteristics
      that warrant further studies to examine the pathophysiological role of UA in
      different disease processes.

PMID- 22465910
TI  - A meta-analysis on alcohol drinking and the risk of Hodgkin lymphoma.
AB  - The role of alcohol intake in the risk of Hodgkin lymphoma (HL) is still largely
      unclear. To summarize the evidence on the issue, we carried out a meta-analysis
      of the available studies. We identified eight case-control and two cohort
      studies, including a total of 1488 cases of HL. We derived meta-analytic
      estimates using random-effects models, taking into account the correlation
      between estimates, and carried out a dose-risk analysis using nonlinear random
      effects metaregression models. Compared with nondrinkers, the relative risk for
      alcohol consumers was 0.70 [95% confidence interval (CI), 0.60-0.81] overall,
      0.66 (95% CI, 0.56-0.78) among case-control, and 0.92 (95% CI, 0.63-1.33) among
      cohort studies. Compared with nondrinkers, the pooled relative risks were 0.71
      (95% CI, 0.57-0.89) for light (i.e. <=1 drink/day) and 0.73 (95% CI, 0.60-0.87)
      for moderate-to-heavy (i.e. >1 drink/day) alcohol drinking. This meta-analysis
      suggests a favourable effect of alcohol on HL, in the absence, however, of a dose
      risk relationship. The inverse association was restricted to--or greater in--case
      control as compared with cohort studies. This indicates caution in the
      interpretation of results.

PMID- 22465911
TI  - Annual or biennial CT screening versus observation in heavy smokers:  5-year
      results of the MILD trial.
AB  - The efficacy and cost-effectiveness of low-dose spiral computed tomography (LDCT)
      screening in heavy smokers is currently under evaluation worldwide. Our screening
      program started with a pilot study on 1035 volunteers in Milan in 2000 and was
      followed up in 2005 by a randomized trial comparing annual or biennial LDCT with
      observation, named Multicentric Italian Lung Detection. This included 4099
      participants, 1723 randomized to the control group, 1186 to biennial LDCT
      screening, and 1190 to annual LDCT screening. Follow-up was stopped in November
      2011, with 9901 person-years for the pilot study and 17 621 person-years for
      Multicentric Italian Lung Detection. Forty-nine lung cancers were detected by
      LDCT (20 in biennial and 29 in the annual arm), of which 17 were identified at
      baseline examination; 63% were of stage I and 84% were surgically resectable.
      Stage distribution and resection rates were similar in the two LDCT arms. The
      cumulative 5-year lung cancer incidence rate was 311/100 000 in the control
      group, 457 in the biennial, and 620 in the annual LDCT group (P=0.036); lung
      cancer mortality rates were 109, 109, and 216/100 000 (P=0.21), and total
      mortality rates were 310, 363, and 558/100 000, respectively (P=0.13). Total
      mortality in the pilot study was similar to that observed in the annual LDCT arm
      at 5 years. There was no evidence of a protective effect of annual or biennial
      LDCT screening. Furthermore, a meta-analysis of the four published randomized
      trials showed similar overall mortality in the LDCT arms compared with the
      control arm.

PMID- 22465912
TI  - Inhibition of return: a "depth-blind" mechanism?
AB  - When attention is oriented to a peripheral visual event, observers respond faster
      to stimuli presented at a cued location than at an uncued location. Following
      initial reaction time facilitation responses are slower to stimuli subsequently
      displayed at the cued location, an effect known as inhibition of return (IOR).
      Both facilitatory and inhibitory effects have been extensively investigated in
      two-dimensional space. Facilitation has also been documented in three-dimensional
      space, however the presence of IOR in 3D space is unclear, possibly because IOR
      has not been evaluated in an empty 3D space. Determining if IOR is sensitive to
      the depth plane of stimuli or if only their bi-dimensional location is inhibited
      may clarify the nature of the IOR. To address this issue, we used an attentional
      cueing paradigm in three-dimensional (3D) space. Results were obtained from
      fourteen participants showed IOR components in 3D space when binocular disparity
      was used to induce depth. We conclude that attentional orienting in depth
      operates as efficiently as in the bi-dimensional space.

PMID- 22465913
TI  - [Photonics meets sensing of bio-reaction and cell dynamics].

PMID- 22465914
TI  - [Highly sensitive intraoperative detection of tiny tumors with novel
      "activatable" fluorescence probes].
AB  - Several versatile and rational design strategies for novel fluorescence probes
      including those based on photoinduced electron transfer have been successfully
      established. Indeed, based on these design strategies, various novel fluorescence
      probes were successfully developed including those for reactive oxygen species
      and reporter enzymes. Furthermore, we have succeeded to visualize tiny tumors in
      living mice by using cancer-specific antibodies tagged with acidic-pH activatable
      fluorescence probes. Here, I will describe the details of probe design as well as
      some imaging results with living cells and animals by applying our novel
      fluorescence probes.

PMID- 22465915
TI  - [Photosensing by membrane-embedded receptors and its application for the life
      scientists].
AB  - Light is one of the most important energy sources and signals providing critical
      information to biological systems. The photoreceptor rhodopsin, which possesses
      retinal chromophore (vitamin A aldehyde) surrounded by seven transmembrane alpha
      helices, is widely dispersed in prokaryotes and in eukaryotes. Although rhodopsin
      molecules work as distinctly different photoreceptors, they can be divided
      according to their two basic functions such as light-energy conversion and light
      signal transduction. Thus rhodopsin molecules have great potential for
      controlling cellular activity by light. Indeed, a light-energy converter channel
      rhodopsin is used to control neural activity. From 2001, we have been working on
      various microbial sensory rhodopsins functioning as light-signal converters. In
      this review, we will introduce rhodopsin molecules from microbes, and will
      describe artificial and light-dependent protein expression system in Escherichia
      coli using Anabeana sensory rhodopsin (ASR). The newly developed tools would be
      widely useful for life scientists.

PMID- 22465916
TI  - [Modulation of growth factor receptors in membrane microdomains].
AB  - Membrane lateral heterogeneity is accepted as a requirement for the function of
      biological membranes, and the notion of the "raft/microdomain" gives specificity
      to this concept. Recently, fluorescence-based techniques such as fluorescence
      recovery after photobleaching (FRAP), single particle tracking (SPT), and
      fluorescence correlation spectroscopy (FCS) have shown promise for application to
      the dynamics of membrane molecules in microdomains. We previously revealed, by
      performing live-cell FRAP and SPT studies, a mechanism of insulin resistance in
      which dissociation of the insulin receptor (IR)-caveolin-1 (Cav1) complex was
      caused by an interaction between the IRbeta subunit and the ganglioside GM3
      cluster, a glycolipid-enriched membrane microdomain. We hoped to demonstrate that
      an alteration in the lipid component of microdomains affects lateral diffusion of
      membrane receptors. We therefore established an experimental system for
      monitoring the membrane organization of receptors by analyzing their lateral
      diffusion parameters in the plasma membranes of living cells using FRAP and SPT.
      In this study, measurement of the lateral diffusion of the IR was performed by
      fitting analysis to fluorescence recovery curves and trace analysis to individual
      fluorescent spots, which provided the diffusion constant. The results show how
      fast IR molecules diffuse before and after a change in membrane environment, such
      as stimulation by cholesterol depression or treatment with a glycosphingolipid
      (GSL) inhibitor. Using these techniques, we have established a method for
      determining the diffusion constant for the lateral movement of IR-EGFP, expressed
      in CHO-K1 cells. We will use these techniques for the lateral diffusion analysis
      of membrane receptors under other assay conditions, such as use of GSL-deficient
      cells or pathologic samples.

PMID- 22465917
TI  - [In vivo imaging reveals adipose tissue inflammation in obesity and multi
      cellular processes of developing thrombus].
AB  - The metabolic syndrome is a major risk factor of cardiovascular events, and obese
      visceral adipose tissue remodeling based on chronic inflammation plays a central
      role. To assess dynamic interplay between multiple cell types in obese adipose
      tissue, a visualization technique in vivo was developed. By this technique we
      identified inflammatory cell clusters associated with angiogenesis and
      adipogenesis in obese adipose tissue. We also found increased leukocyte-platelet
      endothelial cell interactions in obese adipose tissue microcirculation, which
      were indicative of local chronic inflammation. Moreover, we found that large
      numbers of CD8(+) effector T cells infiltrated into obese adipose tissue.
      Immunological and genetic depletion of CD8(+) T cells reduced inflammatory (M1)
      macrophage infiltration and adipose tissue inflammation, and ameliorated systemic
      insulin resistance. Infiltration of CD8(+) T cells is essential for inflammatory
      macrophage recruitment into obese adipose tissue, and the initiation and
      development of inflammation therein. Our results clearly demonstrate the power of
      our imaging technique to analyze complex cellular interplay in vivo, especially
      parenchymal and stromal cell crosstalk, and to evaluate new therapeutic
      interventions against conditions arising from these interactions.

PMID- 22465918
TI  - [Development of fluorescent labeling methods for stem cells].
AB  - For successful development of cell-based therapy, both the disposition and
      differentiation of transplanted cells are directly related to therapeutic
      effects. In vivo imaging is an attractive tool to obtain real-time information on
      the disposition of target cells. In various types of imaging methods such as
      positron emission tomography(PET) and magnetic resonance imaging(MRI),
      fluorescence imaging is suitable for visualizing the disposition of cells because
      it can visualize single cells both in vitro and in vivo. For the trafficking of
      stem cells after transplantation, it is necessary to label living cells for long
      time periods without disturbing the function or differentiation of the labeled
      cells. Recently, we have developed quantum dots modified with
      polyamidoamine(PAMAM) dendrimers. These can more rapidly escape from endosomes
      and sustain their fluorescence intensity compared with unmodified quantum dots in
      primary cultured mesenchymal stem cells (MSCs). Fluorescence intensity was also
      sustained after intravenous injection of MSCs labeled with PAMAM dendrimer
      modified quantum dots. To study the dynamics of MSCs in vivo, we constructed a
      piggyBack transposon vector that can integrate the target gene into the genome in
      mammalian cells, and established primary MSCs with long-term expression of EmGFP.
      In addition, we also developed a suction device stabilizing tissue for in vivo
      real time imaging. In this section, I present our recent findings on long-term
      fluorescent labeling of MSCs and in vivo visualizing of cell dynamics in a living
      mouse.

PMID- 22465919
TI  - [What is chronic kidney disease (CKD)?: early check and early treatment of kidney
      disease].

PMID- 22465920
TI  - [Methylarginies-induced endothelial dysfunction in chronic kidney disease].
AB  - Chronic kidney disease (CKD), defined as low glomerular filtration rates and/or
      the presence of albuminuria, is considered a risk factor for cardiovascular
      disease (CVD). In recent years, increasing emphasis has been placed on
      endothelial dysfunction as a key element underlying the relationship between CKD
      and CVD. Endothelial cells play a pivotal role in many aspects of vascular
      function by generating nitric oxide (NO). However, NO production is reduced in
      CKD patients, partially due to decreased endothelial NO production. One possible
      cause of NO deficiency is increased levels of endogenous NO synthase inhibitors,
      in particular asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA
      are consequence of increased synthesis and reduced degradation. Accumulation of
      ADMA and inhibition of NO production might contribute to endothelial dysfunction,
      hypertension, initiation of atherosclerosis, and incidence of CVD. Clinical
      studies revealed that ADMA plasma concentration is increased in populations with
      renal disease, vascular diseases, and high cardiovascular risks. In this regard,
      ADMA is increasingly recognized as a biomarker of CKD and CVD. This review
      discusses ADMA-mediated endothelial dysfunction in CKD, especially focusing on
      the link between CKD and CVD.

PMID- 22465921
TI  - [Roles of coagulation pathway and factor Xa in chronic kidney disease (CKD)].
AB  - Considering that fibrin deposition is observed in glomerulonephritis as well as
      in diabetic nephropathy, we performed studies to clarify the roles of the
      coagulation pathway and the active type of coagulation factor X (factor Xa) in
      the development of chronic kidney disease (CKD) using animal models. Factor Xa
      activates various cell types through protease-activated receptor 2 (PAR2).
      Several in vitro studies have demonstrated that PAR2 can mediate factor Xa
      signaling, but not thrombin signaling. Coagulation processes proceed together
      with the extracellular matrix (ECM) accumulation through factor V expression in
      rat Thy-1 nephritis. DX-9065a, a factor Xa inhibitor, suppresses this type of
      glomerulonephritis. The factor Xa inhibitor danaparoid ameliorated proteinuria,
      cellular proliferation, and fibrin deposition in lipopolysaccharide (LPS)
      triggered activation of High IgA (HIGA) strain of ddY mice. Another factor Xa
      inhibitor, fondaparinux, suppressed urinary protein, glomerular hypertrophy, and
      connective tissue growth factor (CTGF), and ECM protein deposition together with
      angiogenesis in diabetic db/db mice. Finally, in the model of peritoneal
      fibrosis, fondaparinux treatment decreased the thickness of submesothelial
      fibrotic tissue and angiogenesis. In consideration of the results to potential
      human therapy, factor Xa regulation may be promising for the treatment of the
      aggravation in glomerulonephritis and of the early phase of diabetic nephropathy.
      In the near future, novel factor Xa inhibitors with the characteristics of oral
      administration and biliary elimination may appear in the clinical use for
      treatment of cardiovascular diseases.

PMID- 22465922
TI  - [Mechanisms responsible for the renoprotective effects of renin-angiotensin
      inhibitors].
AB  - In recent years, the focus of interest on the role of the renin-angiotensin
      system (RAS) in the pathophysiology of hypertension and organ injury has changed
      to a major emphasis on the role of the local RAS in specific tissues. In the
      kidney, all of the RAS components are present and intrarenal angiotensin II (Ang
      II) is formed by independent multiple mechanisms. Ang II is compartmentalized in
      the renal interstitial fluid and the proximal tubular compartments with much
      higher concentrations than those existing in the circulation. It has also been
      revealed that inappropriate activation of the intrarenal RAS is an important
      contributor to the pathogenesis of chronic kidney disease (CKD). Indeed, most
      national guideline groups now recommend the use of RAS inhibitors in preference
      to other antihypertensive agents for hypertensive patients with CKD. In this
      review, we will briefly summarize our current understanding of independent
      regulation of the intrarenal RAS. We will also discuss the impact of RAS
      inhibitors in preventing the progressive increases in the intrarenal RAS during
      the development of CKD.

PMID- 22465923
TI  - [Appropriate pharmacotherapy in patients with chronic kidney disease - new
      approach - ].
AB  - The kidney is the most important organ for the excretion of drugs. It was
      previously thought that appropriate dosages of these drugs could be easily
      estimated by evaluating the kidney function of patients and the excretion rate of
      the drug. However, the pharmacokinetic characteristics of patients with kidney
      disease are as follows: 1) Active metabolites with a higher polarity can
      accumulate, which can induce unpredictable adverse effects. For example, over
      sedation with morphine or the development of the fatal toxic syndrome in the case
      of allopulinol are due to the accumulation of active metabolites derived from
      these drugs. 2) Although the renal excretion rate of acetoaminophen is only less
      than 5%, the accumulation of its glucuronide conjugate during multiple dosing in
      patients with kidney failure may induce high serum acetoaminophen trough levels
      via the entero-hepatic circulation. 3) Although the renal excretion rate of the
      drugs are negligible, a remarkable increase in the serum levels of certain drugs
      were observed in patients with end stage kidney disease, suggesting a significant
      reduction in non-renal clearance probably by the accumulation of uremic toxins.
      For drugs that are likely to be administered to patients with kidney disease,
      even including drugs that are not excreted by the kidney, a full pharmacokinetic
      study should be conducted in patients and the results carefully assessed.
      Information on dosing adjustments for impaired kidney function based on estimated
      glomerular filtration rates should then be clearly stated in the package insert
      of the drugs.

PMID- 22465924
TI  - [Multilateral proteomic approaches for more rapid drug development].

PMID- 22465925
TI  - [Techniques for rapid production of monoclonal antibodies for use with antibody
      technology].
AB  - A monoclonal antibody (Mab), due to its specific binding ability to a target
      protein, can potentially be one of the most useful tools for the functional
      analysis of proteins in recent proteomics-based research. However, the production
      of Mab is a very time-consuming and laborious process (i.e., preparation of
      recombinant antigens, immunization of animals, preparation of hybridomas), making
      it the rate-limiting step in using Mabs in high-throughput proteomics research,
      which heavily relies on comprehensive and rapid methods. Therefore, there is a
      great demand for new methods to efficiently generate Mabs against a group of
      proteins identified by proteome analysis. Here, we describe a useful method
      called "Antibody proteomic technique" for the rapid generations of Mabs to
      pharmaceutical target, which were identified by proteomic analyses of disease
      samples (ex. tumor tissue, etc.). We also introduce another method to find
      profitable targets on vasculature, which is called "Vascular proteomic
      technique". Our results suggest that this method for the rapid generation of Mabs
      to proteins may be very useful in proteomics-based research as well as in
      clinical applications.

PMID- 22465926
TI  - [Pharmacoproteomic approach by quantitative targeted proteomics].
AB  - Omics analyses provided many candidates for drug targets and biomarkers. However,
      these analyses have not contributed to drug development efficiently because of
      top-down omics analyses. To solve this problem, we have recently developed
      quantitative targeted proteomics with multiplexed-multiple reaction monitoring
      (multiplexed-MRM) method, which enables us to perform bottom-up proteomics. In
      this method, the target proteins for quantification are selected prior to
      analysis based on the knowledge related to interesting phenomena. Target peptides
      for quantification are selected only from sequence information, so time-consuming
      procedures such as antibody preparation and protein purification are unnecessary.
      In this review, we introduce the technical features of multiplexed-MRM method as
      novel protein quantification method, and summarize its advantages with reference
      to recently reported results, including species differences, in vitro-to-in vivo
      reconstruction and personalized chemotherapy. This novel simultaneous protein
      quantification method overcomes problems of antibody-based quantification and
      would open new drug research based of protein as "Pharmacoproteomics".

PMID- 22465927
TI  - [Glycomics in quality control of tissue-engineered medical products].
AB  - Glycosylation of cells is known to alter with several biological events such as
      cell differentiations and proliferations as well as some diseases. "Glycomic
      approaches", comprehensive qualitative and quantitative glycan analyses of the
      cells, have become increasingly important as a means of discovering biomarkers
      that have the potential of being used as disease diagnostic markers and molecular
      markers for cell characterizations. In this paper, we introduce a method of
      quantitative glycan profiling by liquid chromatography/mass spectrometry with a
      combination of an isotope tagging method. In addition, we demonstrate the
      potential of glycan profiling as a tool for the identification of differentiated
      human bone marrow mesenchymal stem cell (hMSC) and non-differentiated hMSC.

PMID- 22465928
TI  - [Imaging mass spectrometry].
AB  - Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry
      (IMS) enables the visualization of the distribution of a range of biomolecules
      that have varied structures in the cells and tissue sections. This emerging
      imaging technique was initially developed as a tool for protein imaging, but
      recently it is increasingly being used for the imaging of small organic
      molecules. IMS is an effective technique for the imaging of small metabolites,
      including endogenous metabolites such as lipids and exogenous drugs because of
      the following advantages: First, IMS does not require any specific labels or
      probes. Second, IMS is a non-targeted imaging method. Finally, the simultaneous
      imaging of many types of metabolite molecules is possible, and all these features
      are necessary for the assessment of metabolite localization. In this review, we
      discuss the capability of current IMS techniques for imaging small molecules, and
      introduce representative studies on imaging of endogenous and exogenous
      metabolites. In addition, the limitations and problems of the technique are also
      discussed, and reports of progress toward solving the problems with this
      technique are also introduced.

PMID- 22465929
TI  - [Establishment of the background color to make discrimination of domestic ethical
      tablets sharper and more feasible based on the analysis of their color
      distribution].
AB  - In Japan, pharmacists as well as patients often have problems distinguishing one
      ethical tablet from another because they can be very similar in color. In an
      attempt to solve this problem, we hypothesized using a background sheet of dark
      gray identified by N3.5 on the Munsell color system (Munsell CS). The colors of
      369 and 656 ethical tablets in Japan and the USA, respectively, were measured. On
      the Munsell CS, the Japanese tablets were localized mostly in the range of hues
      between 10R~10Y with values ? 8 and chroma ? 4, while the colors of the American
      tablets were scattered over the hue spectrum with a variety of values and chroma.
      Based on these findings, we examined the effects of background colors on
      discrimination between 5 tablets classified into yellow, yellow red, red, or
      mixed groups that represented typical domestic Japanese tablets. Background
      colors of light, medium, and dark gray, purple, blue, and blue green were
      selected based on a general concept on color discrimination. The influence of
      white 10 mm-ruled squares on background sheets was examined as well. Under JIS
      Z8723 conditions, 42 volunteers used a 4-point scale to evaluate how clearly they
      could discriminate between each set of tablets on each of the background sheets.
      Variance analysis of the obtained data with SPSS demonstrated that with healthy
      vision, use of a dark gray background sheet with or without ruled squares enabled
      the sharpest and most feasible discrimination between all sets of tablets. A
      similar test with dark gray and white clearly demonstrated that the former works
      as a practical background color for discrimination among different domestic
      Japanese tablets.

PMID- 22465930
TI  - [Study of factors affecting drug extraction during continuous hemofiltration and
      hemodiafiltration, and the contribution of extraction to systemic clearance].
AB  - The aim of this study was to elucidate the factors affecting dialysis clearance
      and the need for additional doses of drugs during and after continuous
      hemofiltration (CHF) and hemodiafiltration (CHDF). We performed a literature
      search of MEDLINE using the terms hemofiltration OR hemodiafiltration AND
      pharmacokinetics to obtain the clearances of CHF and CHDF in a clinical setting.
      The relationships between molecular weight, the unbound fraction (fuB),
      ultrafiltration flow rate (UFR) and dialysis flow rate were analyzed. The need
      for additional doses of certain drugs was also discussed based on the ratio of
      dialysis and systemic clearances. The clearance of CHF for 32 reported drugs was
      significantly correlated with the product of fuB*UFR (r=0.841, p<0.001), and
      furthermore the plots obtained lay on a line of y=x. The clearance of CHDF also
      showed good correlation with the product of fuB*UFR (r=0.795, p<0.001), but the
      plots were higher than the line for y=x, suggesting that additional clearance by
      dialysis was not negligible. The elimination by both forms of dialysis for drugs
      excreted mainly via the kidneys, and with a higher fuB, was considerable. The
      extent of drug clearance by both CHF and CHDF is determined mainly by fuB and
      UFR. The ratio of dialysis clearance to systemic clearance should be estimated to
      determine the contribution of CHF and CHDF.

PMID- 22465931
TI  - [Evaluation and improvement of a measure of drug name similarity, vwhtfrag, in
      relation to subjective similarities and experimental error rates].
AB  - Confusion of drug names is one of the most common causes of drug-related medical
      errors. A similarity measure of drug names, "vwhtfrag", was developed to
      discriminate whether drug name pairs are likely to cause confusion errors, and to
      provide information that would be helpful to avoid errors. The aim of the present
      study was to evaluate and improve vwhtfrag. Firstly, we evaluated the correlation
      of vwhtfrag with subjective similarity or error rate of drug name pairs in
      psychological experiments. Vwhtfrag showed a higher correlation to subjective
      similarity (college students: r=0.84) or error rate than did other conventional
      similarity measures (htco, cos1, edit). Moreover, name pairs that showed
      coincidences of the initial character strings had a higher subjective similarity
      than those which had coincidences of the end character strings and had the same
      vwhtfrag. Therefore, we developed a new similarity measure (vwhtfrag+), in which
      coincidence of initial character strings in name pairs is weighted by 1.53 times
      over coincidence of end character strings. Vwhtfrag+ showed a higher correlation
      to subjective similarity than did unmodified vwhtfrag. Further studies appear
      warranted to examine in detail whether vwhtfrag+ has superior ability to
      discriminate drug name pairs likely to cause confusion errors.

PMID- 22465932
TI  - Interobserver variability in the interpretation of colon manometry studies in
      children.
AB  - OBJECTIVES: The aim of the present study was to evaluate the variability in
      interpretation of colon manometry (CM) in children. METHODS: Fifty-seven colon
      motility studies were independently reviewed by 5 observers. Each observer was
      required to report on the colonic motility during fasting, after administration
      of a meal, and after bisacodyl stimulation. They were also asked to comment
      whether CM study was normal or abnormal and whether in their opinion the
      postprandial recording provided clinically useful information. RESULTS: The
      median (range) agreement regarding the presence of high-amplitude propagating
      contractions (HAPC) was 83% (80%-92%). The interpretation of gastrocolonic
      response produced the most inconsistent results with median (range) agreemnet of
      64% (53%-95%). The postprandial period was reported to be useful in only 3% to
      24% of the studies. The median (range) agreement regarding the overall
      interpretation of the study being either normal or abnormal was 87% (83%-90%).
      CONCLUSIONS: The most easily recognizable contraction pattern during CM is the
      high-amplitude propagating contractions. Visual interpretation of the
      gastrocolonic response produces the most inconsistent results and maximum
      variability. Abbreviated CM studies without the postprandial period or routine
      calculation of the motility index to evaluate gastrocolonic response can help
      make colon manometries more objective and reliable.

PMID- 22465933
TI  - Pancreatic autoantibodies and autoantibodies against goblet cells in pediatric
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Significance of pancreatic autoantibodies determined by using
      exocrine pancreas (PAB) and antibodies against recombinant pancreas antigen
      (rPAB), as well as the importance of autoantibodies against goblet cells (GAB),
      is not known in pediatric patients with inflammatory bowel disease (IBD). Our aim
      was to determine the complex analysis of PAB, rPAB, GAB, antibodies against
      Saccharomyces cerevisiae, and perinuclear components of neutrophils in pediatric
      patients with IBD. Moreover, association with NOD2/CARD15 and disease phenotype
      was determined. METHODS: A total of 152 pediatric patients (median age 13.9
      years) with IBD (103 patients with Crohn disease [CD] and 49 patients with
      ulcerative colitis [UC]) and 104 controls were included. Serum autoantibodies
      were determined by indirect immunofluorescence assay. NOD2/CARD15 variants were
      tested by polymerase chain reaction/restriction fragment length polymorphism.
      RESULTS: The presence of PAB and rPAB was significantly higher in CD (34% and
      35.9%) and in UC (20.4% and 24.5%) compared with pediatric control cohort (0% and
      0%, P<0.0001). In addition, GAB positivity was significantly increased in
      patients with UC in comparison with CD and controls, respectively (UC, 12.2%; CD,
      1.9%; controls, 1.9%; P=0.02). Specificity of PAB and rPAB was 100%; however,
      sensitivity was low. The combination of PAB and/or antibodies against
      Saccharomyces cerevisiae/perinuclear components of neutrophils improved the
      sensitivity of serological markers in CD (87.4%) and in UC (79.6%); specificities
      were 89.3% and 93.2%, respectively. Pancreatic autoantibodies (PAB, rPAB) and GAB
      were not related to clinical presentation, medical therapy, or need for surgery
      in CD or in UC. CONCLUSIONS: Pancreatic autoantibodies and GAB were specific for
      IBD, but the sensitivity was limited as well because there was lack of
      correlation with clinical phenotype. Combinations of these antibodies have shown
      increased sensitivity; therefore, it may be recommended in the diagnostic
      procedure of IBD.

PMID- 22465934
TI  - Pancreatic pseudocysts in children:  treatment by endoscopic cyst gastrostomy.
AB  - AIM: The aim of the present study was to review the use of endoscopic cyst
      gastrostomy (E-CG) as a treatment option for pancreatic pseudocysts referred to a
      tertiary paediatric surgical centre. METHODS: Retrospective review during a 10
      year period (January 2001-December 2010). Cyst gastrostomies were performed using
      1 or 2 double pigtailed Zimmon stents (7-10 Fr) under general anaesthesia. Data
      are quoted as median (range). RESULTS: E-CG was performed in 7 (5 males) children
      (median age at presentation 11.7 [8.2-15.8] years). Pancreatic pseudocysts were
      caused by acute pancreatitis in 5 (gallstones n = 1, hereditary pancreatitis n =
      1, pancreatic divisum n = 1, asparaginase induced n = 1, and idiopathic n = 1)
      and pancreatic trauma in 2 (motor vehicle accident n = 1, and handlebar injury n
      = 1). All of the cases were associated with a rise in serum amylase level, median
      1028 (276-2077) IU/L at the peak of symptoms. Three children had pancreatic duct
      stent placement during endoscopic retrograde cholangiopancreatography as the
      initial therapeutic intervention, but went on to have E-CG later. One who had a
      huge pseudocyst at presentation had already undergone an open cyst gastrostomy,
      which had recurred at 1 month. Rescue E-CG was performed 38 days later. All of
      the stents were removed endoscopically at 8 (6-40) weeks. E-CG was uncomplicated
      and pseudocysts resolved completely in 5. One required repeat placement at 15
      days due to catheter slippage with later full resolution. One child required open
      cyst gastrostomy due to reaccumulation two months following removal of the stent.
      Median hospital stay post E-CG was 3 (1-23) days. There has been no recurrence at
      median follow-up of 18 (5-108) months. CONCLUSIONS: Endoscopic cyst gastrostomy
      is a safe and effective alternative for the management of pancreatic pseudocysts
      in children and should now be considered as treatment of choice.

PMID- 22465935
TI  - Comparison of sequential and standard therapy for Helicobacter pylori eradication
      in children and investigation of clarithromycin resistance.
AB  - AIMS: The aim of the present study was to compare the efficacy of sequential and
      standard triple-drug regimen for Helicobacter pylori (H pylori) eradication in
      children and to determine the primary resistance rate to clarithromycin. METHODS:
      Children with H pylori infection randomized to receive either standard regimen (n
      = 28) consisting of lansoprazole for 30 days, amoxicillin and clarithromycin for
      14 days or sequential regimen (n = 16) consisting of lansoprazole for 30 days,
      amoxicillin for 7 days, followed by clarithromycin and metronidazole for the next
      7 days. Clarithromycin susceptibility of H pylori was assessed with fluorescence
      in-situ hybridization technique. Eradication was controlled by C urea breath test
      or monoclonal stool antigen test 4 weeks after the end of the therapy. RESULTS: H
      pylori eradication rate was higher in the sequential therapy group (93.7%),
      compared with the standard therapy group (46.4%) (P = 0.002). There was no
      difference in adverse drug reactions and in compliance to the treatment between
      the groups. Primary clarithromycin resistance rate for H pylori was found as
      25.7% (n = 9). All of the patients having clarithromycin resistance were
      coincidentally in the standard therapy group. After the exclusion of these 9
      patients, sequential therapy was again found to be more effective than the
      standard therapy (P = 0.02). CONCLUSIONS: Sequential therapy seems highly
      effective for eradicating H pylori in children; however, the difference between 2
      groups in resistant strains was the limitation of the study. Our country needs to
      reassess the effectiveness of standard triple therapy regimen for H pylori
      eradication.

PMID- 22465936
TI  - Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing
      proliferation and metastasis of colorectal cancer using non-invasive
      bioluminescence imaging.
AB  - In continuation to our studies toward the identification of direct anti-cancer
      targets, here we showed that destruxin B (DB) from Metarhizium anisopliae
      suppressed the proliferation and induced cell cycle arrest in human colorectal
      cancer (CRC) HT29, SW480 and HCT116 cells. Additionally, DB induced apoptosis in
      HT29 cells by decreased expression level of anti-apoptotic proteins Bcl-2 and Bcl
      xL while increased pro-apoptotic Bax. On the other hand, DB attenuated Wnt
      signaling by downregulation of beta-catenin, Tcf4 and beta-catenin/Tcf4
      transcriptional activity, concomitantly with decreased expression of beta-catenin
      target genes cyclin D1, c-myc and survivin. Furthermore, DB affected the
      migratory and invasive ability of HT29 cells through suppressed MMPs-2 and -9
      enzymatic activities. We also found that DB targeted the MAPK and/or PI3K/Akt
      pathway by reduced expression of Akt, IKK-alpha, JNK, NF-kappaB, c-Jun and c-Fos
      while increased that of IkappaBalpha. Finally, we demonstrated that DB inhibited
      tumorigenesis in HT29 xenograft mice using non-invasive bioluminescence
      technique. Consistently, tumor samples from DB-treated mice demonstrated
      suppressed expression of beta-catenin, cyclin D1, survivin, and endothelial
      marker CD31 while increased caspase-3 expression. Collectively, our data supports
      DB as an inhibitor of Wnt/beta-catenin/Tcf signaling pathway that may be
      beneficial in the CRC management.

PMID- 22465937
TI  - Metabolism of bilirubin by human cytochrome P450 2A6.
AB  - The mouse cytochrome P450 (CYP) 2A5 has recently been shown to function as
      hepatic "Bilirubin Oxidase" (Abu-Bakar, A., et al., 2011. Toxicol. Appl.
      Pharmacol. 257, 14-22). To date, no information is available on human CYP
      isoforms involvement in bilirubin metabolism. In this paper we provide novel
      evidence for human CYP2A6 metabolising the tetrapyrrole bilirubin. Incubation of
      bilirubin with recombinant yeast microsomes expressing the CYP2A6 showed that
      bilirubin inhibited CYP2A6-dependent coumarin 7-hydroxylase activity to almost
      100% with an estimated K(i) of 2.23 MUM. Metabolite screening by a high
      performance liquid chromatography/electrospray ionisation mass spectrometry
      indicated that CYP2A6 oxidised bilirubin to biliverdin and to three other smaller
      products with m/z values of 301, 315 and 333. Molecular docking analyses
      indicated that bilirubin and its positively charged intermediate interacted with
      key amino acid residues at the enzyme's active site. They were stabilised at the
      site in a conformation favouring biliverdin formation. By contrast, the end
      product, biliverdin was less fitting to the active site with the critical central
      methylene bridge distanced from the CYP2A6 haem iron facilitating its release.
      Furthermore, bilirubin treatment of HepG2 cells increased the CYP2A6 protein and
      activity levels with no effect on the corresponding mRNA. Co-treatment with
      cycloheximide (CHX), a protein synthesis inhibitor, resulted in increased half
      life of the CYP2A6 compared to cells treated only with CHX. Collectively, the
      observations indicate that the CYP2A6 may function as human "Bilirubin Oxidase"
      where bilirubin is potentially a substrate and a regulator of the enzyme.

PMID- 22465938
TI  - A novel "pro-sensitizer" based sensing of enzymes using Tb(III) luminescence in a
      hydrogel matrix.
AB  - Chemically synthesized "pro-sensitizers" release the sensitizer in the presence
      of lipase or beta-glucosidase, triggering a significant luminescence response
      from a lanthanide based hydrogel.

PMID- 22465939
TI  - Electrical detection of single pollen allergen particles using electrode-embedded
      microchannels.
AB  - We report on the development of a microfluidic system for the electrical
      detection of single pollen allergen particles. Our device consists of 500 nm
      electrode gaps fabricated in an 800 nm wide fluidic channel. We flowed pollen
      allergen particles of average size 330 nm along the channel via fluid pumping and
      simultaneously monitored temporal change in dc current flowing through the
      sensing electrodes. Current spikes were detected, which can be attributed to a
      capacitance discharging upon trapping/detrapping of single allergens in the
      electrode gap. This sensing mechanism may open new avenues for a highly sensitive
      pollen allergen sensor.

PMID- 22465940
TI  - The emerging role of acyl-CoA thioesterases and acyltransferases in regulating
      peroxisomal lipid metabolism.
AB  - The importance of peroxisomes in lipid metabolism is now well established and
      peroxisomes contain approximately 60 enzymes involved in these lipid metabolic
      pathways. Several acyl-CoA thioesterase enzymes (ACOTs) have been identified in
      peroxisomes that catalyze the hydrolysis of acyl-CoAs (short-, medium-, long- and
      very long-chain), bile acid-CoAs, and methyl branched-CoAs, to the free fatty
      acid and coenzyme A. A number of acyltransferase enzymes, which are structurally
      and functionally related to ACOTs, have also been identified in peroxisomes,
      which conjugate (or amidate) bile acid-CoAs and acyl-CoAs to amino acids,
      resulting in the production of amidated bile acids and fatty acids. The function
      of ACOTs is to act as auxiliary enzymes in the alpha- and beta-oxidation of
      various lipids in peroxisomes. Human peroxisomes contain at least two ACOTs
      (ACOT4 and ACOT8) whereas mouse peroxisomes contain six ACOTs (ACOT3, 4, 5, 6, 8
      and 12). Similarly, human peroxisomes contain one bile acid-CoA:amino acid N
      acyltransferase (BAAT), whereas mouse peroxisomes contain three acyltransferases
      (BAAT and acyl-CoA:amino acid N-acyltransferases 1 and 2: ACNAT1 and ACNAT2).
      This review will focus on the human and mouse peroxisomal ACOT and
      acyltransferase enzymes identified to date and discuss their cellular
      localizations, emerging structural information and functions as auxiliary enzymes
      in peroxisomal metabolic pathways.

PMID- 22465941
TI  - Arterial spin labeling fMRI measurements of decreased blood flow in primary
      visual cortex correlates with decreased visual function in human glaucoma.
AB  - PURPOSE: Altered metabolic activity has been identified as a potential
      contributing factor to the neurodegeneration associated with primary open angle
      glaucoma (POAG). Consequently, we sought to determine whether there is a
      relationship between the loss of visual function in human glaucoma and resting
      blood perfusion within primary visual cortex (V1). METHODS: Arterial spin
      labeling (ASL) functional magnetic resonance imaging (fMRI) was conducted in 10
      participants with POAG. Resting cerebral blood flow (CBF) was measured from
      dorsal and ventral V1. Behavioral measurements of visual function were obtained
      using standard automated perimetry (SAP), short-wavelength automated perimetry
      (SWAP), and frequency-doubling technology perimetry (FDT). Measurements of CBF
      were compared to differences in visual function for the superior and inferior
      hemifield. RESULTS: Differences in CBF between ventral and dorsal V1 were
      correlated with differences in visual function for the superior versus inferior
      visual field. A statistical bootstrapping analysis indicated that the observed
      correlations between fMRI responses and measurements of visual function for SAP
      (r=0.49), SWAP (r=0.63), and FDT (r=0.43) were statistically significant (all
      p<0.05). CONCLUSIONS: Resting blood perfusion in human V1 is correlated with the
      loss of visual function in POAG. Altered CBF may be a contributing factor to
      glaucomatous optic neuropathy, or it may be an indication of post-retinal
      glaucomatous neurodegeneration caused by damage to the retinal ganglion cells.

PMID- 22465942
TI  - Neuroprotective and anticonvulsant effects of organic and conventional purple
      grape juices on seizures in Wistar rats induced by pentylenetetrazole.
AB  - Epilepsy is the most common neurological disorder worldwide. Studies have shown
      that recurrent seizures may increase the concentration of reactive oxygen
      species, which can lead to oxidative stress and neuronal damage. These seizures
      result in substantial deleterious effects on an individual's health. Organic and
      conventional grape juices are rich in polyphenols, compounds with important
      antioxidant activity. However, these juices could have differences in their
      polyphenol content. The aim of this study was to investigate the neuroprotective
      and anticonvulsant effects of organic and conventional grape juice treatments in
      Wistar rats against pentylenetetrazole (a convulsant drug)-induced damage. In
      addition, we evaluated potential behavioral changes in rats treated with the
      juices and the polyphenolic profile of those samples. Animals (n=16 in each
      group) received treatment with saline, organic or conventional grape juice for 17
      days. On the eighteenth day, behavioral changes were evaluated by an open field
      test. Afterwards, half of the rats from each group received pentylenetetrazole
      and were observed for 30 min to evaluate possible seizure characteristics. The
      animals were subsequently killed by decapitation and their hippocampus,
      cerebellum and cerebral cortex tissues were isolated. The results of this study
      showed that neither organic nor conventional grape juice altered the behavior
      parameters, and no statistical differences were observed in the seizure
      characteristics of the groups. Nevertheless, both juice types were able to
      protect from lipid and protein oxidative damage, decrease nitric oxide content
      and increase enzymatic (superoxide dismutase and catalase) and non-enzymatic
      (sulfhydryl protein) antioxidant defenses in brain tissues following
      pentylenetetrazole-induced seizures. In general, organic juice showed superior
      results in each test, probably due to its higher polyphenol content relative to
      conventional juice. These results indicate that grape juices can provide further
      insight into natural neuroprotective compounds and may lead to the development of
      new therapeutic strategies for epileptic patients.

PMID- 22465943
TI  - MicroRNA expression profiling of NGF-treated PC12 cells revealed a critical role
      for miR-221 in neuronal differentiation.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that control protein expression
      through translational inhibition or mRNA degradation. MiRNAs have been implicated
      in diverse biological processes such as development, proliferation, apoptosis and
      differentiation. Upon treatment with nerve growth factor (NGF), rat
      pheochromocytoma PC12 cells elicit neurite outgrowth and differentiate into
      neuron-like cells. NGF plays a critical role not only in neuronal differentiation
      but also in protection against apoptosis. In an attempt to identify NGF-regulated
      miRNAs in PC12 cells, we performed miRNA microarray analysis using total RNA
      harvested from cells treated with NGF. In response to NGF treatment, expression
      of 8 and 12 miRNAs were up- and down-regulated, respectively. Quantitative RT-PCR
      analysis of 11 out of 20 miRNAs verified increased expression of miR-181a(*), miR
      221 and miR-326, and decreased expression of miR-106b(*), miR-126, miR-139-3p,
      miR-143, miR-210 and miR-532-3p after NGF treatment, among which miR-221 was
      drastically up-regulated. Functional annotation analysis of potential target
      genes of 7 out of 9 miRNAs excluding the passenger strands (*) revealed that NGF
      may regulate expression of various genes by controlling miRNA expression,
      including those whose functions and processes are known to be related to NGF.
      Overexpression of miR-221 induced neuronal differentiation of PC12 cells in the
      absence of NGF treatment, and also enhanced neuronal differentiation caused by
      low-dose NGF. Furthermore, miR-221 potentiated formation of neurite network,
      which was associated with increased expression of synapsin I, a marker for
      synapse formation. More importantly, knockdown of miR-221 expression by antagomir
      attenuated NGF-mediated neuronal differentiation. Finally, miR-221 decreased
      expression of Foxo3a and Apaf-1, both of which are known to be involved in
      apoptosis in PC12 cells. Our results suggest that miR-221 plays a critical role
      in neuronal differentiation as well as protection against apoptosis in PC12
      cells.

PMID- 22465944
TI  - Antecedent bradycardia and in-hospital cardiopulmonary arrest mortality in
      telemetry-monitored patients outside the ICU.
AB  - BACKGROUND: Patients with in-hospital cardiopulmonary arrest (IHCA) precipitated
      by respiratory insufficiency often exhibit bradycardia before the arrest. We
      hypothesized that bradycardia frequently occurs in the 10 min preceding IHCA and
      is associated with poor outcomes when IHCA occurs outside the intensive care unit
      (ICU). OBJECTIVES: To determine the prevalence and association of antecedent
      bradycardia with outcome in adult patients with IHCA occurring outside the ICU.
      METHODS: We performed a retrospective cohort study among telemetry monitored
      adults with IHCA outside the ICU in a two-hospital health system between 2008 and
      2010 with follow-up until their discharge or death in-hospital. We defined (1)
      IHCA as >1 min of chest compressions or trans-thoracic defibrillation, (2)
      Antecedent bradycardia as at least 2 min of continuous heart rate between 1 and
      59 beats per minute in the 10min preceding IHCA, and (3) ventricular
      tachyarrhythmia arrests as presence of sustained ventricular tachyarrhythmia for
      >20 s in the 10 min preceding IHCA. RESULTS: Of 98 IHCAs, 39 (39.8%) survived to
      hospital discharge. Of 98 IHCAs, 53 (54.1%) had antecedent bradycardia. After
      adjusting for potential confounders, antecedent bradycardia was associated with
      death prior to hospital discharge (adjusted OR=3.80, 95% CI: 1.47-9.81, p=0.006).
      Among patients with ventricular tachyarrhythmia arrests, antecedent bradycardia
      was associated with a higher risk of death (OR=13.1, 95% CI 1.92-89.5, p=0.009).
      CONCLUSIONS: Antecedent bradycardia occurred frequently and was associated with
      death prior to hospital discharge in non-ICU hospitalized adults on telemetry
      monitoring who developed IHCA.

PMID- 22465945
TI  - Chest compression quality management and return of spontaneous circulation: a
      matched-pair registry study.
AB  - AIMS: Investigating the effects of any intervention during cardiac arrest remains
      difficult. The ROSC after cardiac arrest score was introduced to facilitate
      comparison of rates of return of spontaneous circulation (ROSC) between different
      ambulance services. To study the influence of chest compression quality
      management (including training, real-time feedback devices, and debriefing) in
      comparison with conventional cardiopulmonary resuscitation (CPR), a matched-pair
      analysis was conducted using data from the German Resuscitation Registry, with
      the calculated ROSC after cardiac arrest score as the baseline. METHODS AND
      RESULTS: Matching for independent ROSC after cardiac arrest score variables
      yielded 319 matched cases from the study period (January 2007-March 2011). The
      score predicted a 45% ROSC rate for the matched pairs. The observed ROSC
      increased significantly with chest compression quality management, to 52%
      (P=0.013; 95% CI, 46-57%). No significant differences were seen in the
      conventional CPR group (47%; 95% CI, 42-53%). The difference between the observed
      ROSC rates was not statistically significant. CONCLUSIONS: Chest compression
      quality management leads to significantly higher ROSC rates than those predicted
      by the prognostic score (ROSC after cardiac arrest score). Matched-pair analysis
      shows that with conventional CPR, the observed ROSC rate was not significantly
      different from the predicted rate. Analysis shows a trend toward a higher ROSC
      rate for chest compression quality management in comparison with conventional
      CPR. It is unclear whether a single aspect of chest compression quality
      management or the combination of training, real-time feedback, and debriefing
      contributed to this result.

PMID- 22465946
TI  - A quantitative review of the profile and time course of symptom change in
      schizophrenia treated with clozapine.
AB  - Contemporary analyses demonstrate an early response to antipsychotic treatment in
      non-refractory schizophrenia. The profile of response to clozapine is unknown. We
      used meta-analytic and statistical procedures to examine the response profile to
      clozapine. We identified 19 unique, randomized, double-blind controlled clinical
      trials with suitable time course data, representing 1745 subjects. Individual
      subject data were available for 419 subjects, obtained from two industry
      sponsored trials. Symptom severity scores from the BPRS or the PANSS were entered
      into regression analyses to estimate linear and quadratic coefficients of the
      rate of change of symptom severity over 4 weeks. Both linear and quadratic
      regression coefficients for clozapine, and for comparator antipsychotics differed
      significantly from zero (p <= 0.001), indicating early response profiles.
      Compared with other antipsychotic arms, for clozapine the treatment response was
      greater (d = -0.578, p = 0.021), and the linear coefficient was steeper (d = 
      0.502, p = 0.042); the quadratic coefficients indicating attenuation did not
      differ. Analyses of 6-week data and individual subject data from non-refractory
      and refractory trials were consistent with the primary findings. Somewhat
      surprisingly, clozapine shows an early response profile, similar in pattern but
      somewhat larger in magnitude than other antipsychotic drugs.

PMID- 22465947
TI  - A critical review of major mortality risk factors for all-cause mortality in
      first-episode schizophrenia: clinical and research implications.
AB  - A bibliographical search was performed to identify and evaluate the impact in
      first-episode schizophrenia of the major mortality risk factors as described by
      the World Health Organisation (2009). We found that at first diagnosis rates of
      diabetes were only slightly increased, although lipid abnormalities, mild
      hypertension and being overweight were commonly reported. Levels of drug and
      alcohol abuse were high, as were pre-diagnosis rates of smoking, physical
      inactivity and poor cardiorespiratory fitness. During the first year of
      antipsychotic treatment, there were significant increases in the rates of
      hyperglycaemia/diabetes, obesity, lipid abnormalities and hypertension, but no
      changes in fitness levels, smoking or drug and alcohol abuse. In chronic
      schizophrenia, excess cancer and cardiac deaths seem linked in part to
      availability and quality of care. Innate risk factors such as abnormal reelin and
      raised prolactin may also be important. New evidence, such as an inverse
      relationship between body mass index and suicide in the general population,
      suggests accepted wisdom may not apply to patients at high risk of ending their
      own lives. With current knowledge emphasis needs to be placed by early
      intervention services on physical fitness, smoking and other substance misuse,
      diabetes and hypertension, as well as focusing on weight reduction only in the
      obese.

PMID- 22465948
TI  - Non-genomic vasorelaxant effects of 17beta-estradiol and progesterone in rat
      aorta are mediated by L-type Ca2+ current inhibition.
AB  - AIM: The sex hormones 17beta-estradiol (betaES) and progesterone (PRG) induce
      rapid non-genomic vasodilator effects which could be protective for the
      cardiovascular system. The purpose of this study was to analyze the mechanisms
      underlying their vasodilator effect in rat aortic smooth muscle preparations.
      METHODS: Endothelium-denuded aorta artery rings were prepared from male Wistar
      rats and incubated in an organ bath. The contractions of the preparation were
      recorded through isometric transducers. The effects of the hormones on K(+)
      current and L-type Ca(2+) current (LTCC) were analyzed by using the whole cell
      voltage-clamp technique in A7r5 cells. RESULTS: Both betaES and PRG (1-100
      MUmol/L) concentration-dependently relaxed the endothelium-denuded aortic rings
      contracted by (-)-Bay K8644 (0.1 MUmol/L) or by KCl (60 mmol/L). The IC(50)
      values of the two hormones were not statistically different. The K(V) channel
      blocker 4-aminopyridine (2 mmol/L), BK(Ca) channel blocker tetraethylammonium (1
      mmol/L) and K(ATP) channel blocker glibenclamide (10 MUmol/L) did not
      significantly modify the relaxant effect of the hormones. On the other hand, the
      blockage of the intracellular betaES and PRG receptors with estradiol receptor
      antagonists ICI 182,780 (1 MUmol/L) and PRG receptor antagonist mifepristone (30
      MUmol/L), respectively, did not significantly modify the relaxant action of the
      hormones. In A7r5 cells, both the hormones (1-100 MUmol/L) rapidly and reversibly
      inhibited the basal and BAY-stimulated LTCC. However, these hormones had no
      effect on the basal K(+) current. CONCLUSION: The vasorelaxant effects of betaES
      and PRG are due to the inhibition of LTCC. The K(+) channels are not involved in
      the effects.

PMID- 22465949
TI  - Breviscapine inhibits high glucose-induced proliferation and migration of
      cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK
      signaling pathway.
AB  - AIM: To investigate the influences of breviscapine, a flavonoid extracted from
      Erigeron breviscapus, on the proliferation and migration of vascular smooth
      muscle cells (VSMCs) cultured in a high glucose medium and the underlying
      mechanisms. METHODS: VSMCs were isolated from thoracic aortas of male Sprague
      Dawley rats and cultured in vitro. Cell proliferation was evaluated using
      Counting Kit-8 cell viability assay. Cell migration was evaluated using transwell
      migration assay and in vitro scratch assay. The expression and activity of
      protein kinase C-beta2 (PKC-beta2), extracellular signal-regulated kinase 1/2
      (ERK1/2), p38 mitogen-activated protein kinase (p38), and JNK mitogen-activated
      protein kinase (JNK) were measured with Western blotting. RESULTS: Exposure of
      VSMCs to a high glucose (25 mmol/L) medium significantly increased the
      proliferation and migration potential as compared to the control group.
      Pretreatment with breviscapine (65 MUmol/L and 108 MUmol/L) attenuated high
      glucose-enhanced proliferation and migration of VSMCs. Exposure of VSMCs to the
      high glucose medium activated both the PKC-beta2 and ERK1/2 MAPK, but not the p38
      and JNK MAPK. Pretreatment with breviscapine (65 MUmol/L and 108 MUmol/L) blocked
      high glucose-induced increase of the ERK1/2 activity, but not that of the PKC
      beta2 activity. CONCLUSION: Our study demonstrated that breviscapine ameliorates
      high glucose-induced proliferation and migration of VSMCs via inhibiting ERK1/2
      MAPK signaling.

PMID- 22465950
TI  - Inhibition of hypoxia inducible factor-1alpha ameliorates lung injury induced by
      trauma and hemorrhagic shock in rats.
AB  - AIM: Ischemia/reperfusion is an initial triggering event that leads to gut
      induced acute lung injury (ALI). In this study, we investigated whether hypoxia
      inducible factor-1alpha (HIF-1alpha) played a role in the pathogenesis of lung
      injury induced by trauma and hemorrhagic shock (T/HS). METHODS: Male Wistar rats
      underwent laparotomy and hemorrhagic shock for 60 min. Sham-shock animals
      underwent laparotomy but without hemorrhagic shock. After resuscitation for 3 hr,
      the rats were sacrificed. Morphologic changes of the lungs and intestines were
      examined. Bronchoalveolar lavage fluid (BALF) was collected. Lung water content,
      pulmonary myeloperoxidase (MPO) activity and the levels of malondialdehyde (MDA),
      nitrite/nitrate, TNF-alpha, IL-1beta, and IL-6 in the lungs were measured. The
      gene expression of pulmonary HIF-1alpha and iNOS, and HIF-1alpha transcriptional
      activity in the lungs were also assessed. The apoptosis in the lungs was
      determined using TUNEL assay and cleaved caspase-3 expression. RESULTS: Lung and
      intestinal injuries induced by T/HS were characterized by histological damages
      and a significant increase in lung water content. Compared to the sham-shock
      group, the BALF cell counts, the pulmonary MPO activity and the MDA,
      nitrite/nitrate, TNF-alpha, IL-1beta, and IL-6 levels in the T/HS group were
      significantly increased. Acute lung injury was associated with a higher degree of
      pulmonary HIF-1alpha and iNOS expression as well as apoptosis in the lungs.
      Intratracheal delivery of HIF-1alpha inhibitor YC-1 (1 mg/kg) significantly
      attenuated lung injury, and reduced pulmonary HIF-1alpha and iNOS expression and
      HIF-1alpha transcriptional activity in the T/HS group. CONCLUSION: Local
      inhibition of HIF-1alpha by YC-1 alleviates the lung injury induced by T/HS. Our
      results provide novel insight into the pathogenesis of T/HS-induced ALI and a
      potential therapeutic application.

PMID- 22465951
TI  - A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional
      activation.
AB  - The linker histone H1 is a key player in chromatin organization, yet our
      understanding of the regulation of H1 functions by post-translational
      modifications is very limited. We provide here the first functional
      characterization of H1 acetylation. We show that H1.4K34 acetylation (H1.4K34ac)
      is mediated by GCN5 and is preferentially enriched at promoters of active genes,
      where it stimulates transcription by increasing H1 mobility and recruiting a
      general transcription factor. H1.4K34ac is dynamic during spermatogenesis and
      marks undifferentiated cells such as induced pluripotent stem (iPS) cells and
      testicular germ cell tumors. We propose a model for H1.4K34ac as a novel
      regulator of chromatin function with a dual role in transcriptional activation.

PMID- 22465952
TI  - Endosomal sorting by Semaphorin 4A in retinal pigment epithelium supports
      photoreceptor survival.
AB  - Photoreceptor cell death is the hallmark of a group of human inherited retinal
      degeneration. Although the causative genetic mutations are often known, the
      mechanisms leading to photoreceptor degeneration remain poorly defined. Here, we
      show that Semaphorin 4A (Sema4A), a member of axonal guidance molecule
      semaphorin, plays a role in Rab11/FIP2-mediated endosomal sorting in retinal
      pigment epithelial cells to support photoreceptor function. In response to
      oxidative stress, Sema4A switches the endosomal sorting of the lysosomal
      precursor protein prosaposin from the lysosome to the exosomal release, which
      prevents light-induced photoreceptor apoptosis. In the absence of oxidative
      stress, Sema4A sorts retinoid-binding proteins with retinoids between the cell
      surface and endoplasmic reticulum, by which 11-cis-retinal, a chromophore for
      phototransduction, is regenerated and transported back to photoreceptors. Owing
      to defects in these processes, Sema4A-deficient mice exhibit marked photoreceptor
      degeneration. Our findings therefore indicate that Sema4A regulates two distinct
      endosomal-sorting pathways that are critical for photoreceptor survival and
      phototransduction during the transition between daylight and darkness.

PMID- 22465953
TI  - Regulation of SIRT1 activity by genotoxic stress.
AB  - SIRT1 regulates a variety of cellular functions, including cellular stress
      responses and energy metabolism. SIRT1 activity is negatively regulated by DBC1
      (Deleted in Breast Cancer 1) through direct binding. However, how the DBC1-SIRT1
      interaction is regulated remains unclear. We found that the DBC1-SIRT1
      interaction increases following DNA damage and oxidative stress. The stress
      induced DBC1-SIRT1 interaction requires the ATM-dependent phosphorylation of DBC1
      at Thr 454, which creates a second binding site for SIRT1. Finally, we showed
      that the stress-induced DBC1-SIRT1 interaction is important for cell fate
      determination following genotoxic stress. These results revealed a novel
      mechanism of SIRT1 regulation during genotoxic stress.

PMID- 22465955
TI  - Recent developments on polyphenol-protein interactions: effects on tea and coffee
      taste, antioxidant properties and the digestive system.
AB  - Tea and coffee are widely consumed beverages across the world and they are rich
      sources of various polyphenols. Polyphenols are responsible for the bitterness
      and astringency of beverages and are also well known to impart antioxidant
      properties which is beneficial against several oxidative stress related diseases
      like cancer, cardiovascular diseases, and aging. On the other hand, proteins are
      also known to display many important roles in several physiological activities.
      Polyphenols can interact with proteins through hydrophobic or hydrophilic
      interactions, leading to the formation of soluble or insoluble complexes.
      According to recent studies, this complex formation can affect the
      bioavailability and beneficiary properties of both the individual components, in
      either way. For example, polyphenol-protein complex formation can reduce or
      enhance the antioxidant activity of polyphenols; similarly it can also affect the
      digestion ability of several digestive enzymes present in our body. Surprisingly,
      no review article has been published recently which has focused on the progress
      in this area, despite numerous articles having appeared in this field. This
      review summarizes the recent trends and patterns (2005 onwards) in polyphenol
      protein interaction studies focusing on the characterization of the complex, the
      effect of this complex formation on tea and coffee taste, antioxidant properties
      and the digestive system.

PMID- 22465956
TI  - Structural analysis of Shu proteins reveals a DNA binding role essential for
      resisting damage.
AB  - The yeast Shu complex, consisting of the proteins Shu1, Shu2, Psy3, and Csm2,
      maintains genomic stability by coupling post-replication repair to homologous
      recombination. However, a lack of biochemical and structural information on the
      Shu proteins precludes revealing their precise roles within the pathway. Here, we
      report on the 1.9-A crystal structure of the Psy3-Csm2 complex. The crystal
      structure shows that Psy3 forms a heterodimer with Csm2 mainly through a
      hydrophobic core. Unexpectedly, Psy3 and Csm2 share a similar architecture that
      closely resembles the ATPase core domain of Rad51. The L2 loop present in Psy3
      and Csm2 is similar to that of Rad51 and confers the DNA binding activity of the
      Shu complex. As with Rad51, the Shu complex appears to form a nucleoprotein
      filament by binding nonspecifically to DNA. Structure-based mutagenesis studies
      have demonstrated that the DNA binding activity of the Shu complex is essential
      for repair of the methyl methanesulfonate-induced DNA damage. Our findings
      provide good foundations for the understanding of the Srs2 regulation by the Shu
      complex.

PMID- 22465957
TI  - DNA polymerase delta and zeta switch by sharing accessory subunits of DNA
      polymerase delta.
AB  - Translesion DNA synthesis is an important branch of the DNA damage tolerance
      pathway that assures genomic integrity of living organisms. The mechanisms of DNA
      polymerase (Pol) switches during lesion bypass are not known. Here, we show that
      the C-terminal domain of the Pol zeta catalytic subunit interacts with accessory
      subunits of replicative DNA Pol delta. We also show that, unlike other members of
      the human B-family of DNA polymerases, the highly conserved and similar C
      terminal domains of Pol delta and Pol zeta contain a [4Fe-4S] cluster coordinated
      by four cysteines. Amino acid changes in Pol zeta that prevent the assembly of
      the [4Fe-4S] cluster abrogate Pol zeta function in UV mutagenesis. On the basis
      of these data, we propose that Pol switches at replication-blocking lesions occur
      by the exchange of the Pol delta and Pol zeta catalytic subunits on a
      preassembled complex of accessory proteins retained on DNA during translesion DNA
      synthesis.

PMID- 22465958
TI  - Sequence-dependent structural variation in DNA undergoing intrahelical inspection
      by the DNA glycosylase MutM.
AB  - MutM, a bacterial DNA-glycosylase, plays a critical role in maintaining genome
      integrity by catalyzing glycosidic bond cleavage of 8-oxoguanine (oxoG) lesions
      to initiate base excision DNA repair. The task faced by MutM of locating rare
      oxoG residues embedded in an overwhelming excess of undamaged bases is especially
      challenging given the close structural similarity between oxoG and its normal
      progenitor, guanine (G). MutM actively interrogates the DNA to detect the
      presence of an intrahelical, fully base-paired oxoG, whereupon the enzyme
      promotes extrusion of the target nucleobase from the DNA duplex and insertion
      into the extrahelical active site. Recent structural studies have begun to
      provide the first glimpse into the protein-DNA interactions that enable MutM to
      distinguish an intrahelical oxoG from G; however, these initial studies left open
      the important question of how MutM can recognize oxoG residues embedded in 16
      different neighboring sequence contexts (considering only the 5'- and 3'
      neighboring base pairs). In this study we set out to understand the manner and
      extent to which intrahelical lesion recognition varies as a function of the 5'
      neighbor. Here we report a comprehensive, systematic structural analysis of the
      effect of the 5'-neighboring base pair on recognition of an intrahelical oxoG
      lesion. These structures reveal that MutM imposes the same extrusion-prone
      ("extrudogenic") backbone conformation on the oxoG lesion irrespective of its 5'
      neighbor while leaving the rest of the DNA relatively free to adjust to the
      particular demands of individual sequences.

PMID- 22465959
TI  - Effect of vitamin E supplementation on arsenic induced oxidative stress in goats.
AB  - The present study was designed to assess whether supplementation of different
      levels of vitamin E to long-term arsenic exposed goats affords protection against
      the oxidative stress caused by the metalloid. Twenty-four crossbred lactating
      goats were distributed randomly into four groups (control, T(1), T(2) and T(3))
      of six in each. The animals in T(1), T(2) and T(3) were given 50 mg/kg DM arsenic
      daily, while in T(2) and T(3), vitamin E @100 IU and 150 IU/kg DM, respectively,
      was also supplemented additionally for the period of 12 months. Compared to
      control, significant (p < 0.05) decline in SOD (45 %), CAT activities of
      erythrocytes (63 %), plasma total Ig (22 %) and total antioxidant activity (24 %)
      was observed in only arsenic treated groups and vitamin E supplementation in both
      doses produced partial mitigation effect against SOD (23 %, 20 %) and CAT (39 %,
      48 %) while complete mitigation against total Ig (16 %, 7 %) and antioxidant
      activity (10 %, 8 %) was found. Average lymphocyte stimulation index at the end
      of experiment was (p < 0.05) lower in arsenic exposed groups (1.003 +/- 0.01) and
      significant (p < 0.05) recovery was observed in response of vitamin E
      supplementation at higher doses (1.138 +/- 0.03). So, vitamin E is helpful in
      reducing the burden of arsenic induced oxidative stress and activities of
      antioxidant enzymes in goats.

PMID- 22465960
TI  - Ocimum gratissimum Linn. and rosmarinic acid, attenuate eosinophilic airway
      inflammation in an experimental model of respiratory allergy to Blomia
      tropicalis.
AB  - Allergic asthma has emerged as an important public health problem of urban
      populations in developed countries. Very often herbal medicine is used to treat
      this widespread disease, due to the lack of efficacy and the important side
      effects related to the classical drugs in use. Along this line, Ocimum
      gratissimum (Og) is a plant widely used in Brazilian folk medicine to treat
      inflammatory disorders, such as asthma. In the present study we evaluated the
      immunomodulatory effects of Og and rosmarinic acid (RA, a polyphenolic compound)
      in a murine model of respiratory allergy induced by the Blomia tropicalis (Bt)
      mite. The respiratory allergy was induced in A/J mice by administration of Bt
      extract and the treatment was done using 25, 50 or 100mg/kg of an Og methanolic
      extract or using 2, 20 or 200mg/kg of RA. We then evaluated the changes induced
      by these drugs on immunological parameters related to the allergic process, which
      are up-regulated in this allergic model. The treatment of animals with 100mg/Kg
      Og and 200mg/Kg RA led to a significant reduction in the numbers of
      leukocytes/eosinophils in bronchoalveolar lavage (BAL); eosinophil peroxidase
      activity in BAL; presence of mucus in respiratory tract, histopathological
      changes in the lung, and IL-4 in BAL. These results suggest that the methanolic
      extract of Og and the polyphenol RA have therapeutic potential in this murine
      model of respiratory allergy to a clinically relevant human sensitizer allergen.

PMID- 22465961
TI  - Miltefosine enhances phagocytosis but decreases nitric oxide production by
      peritoneal macrophages of C57BL/6 mice.
AB  - Miltefosine is an anticancer drug currently used to treat visceral and cutaneous
      leishmaniasis, also presents a broad-spectrum of fungicidal and antiamoebae
      activities. It acts on the metabolism of phospholipids and glycoproteins of the
      membrane of parasites. Our study aimed to evaluate the effects of miltefosine
      (0.4 to 50.0 MUg/mL) on the phagocytosis and nitric oxide production by
      macrophages of C57BL/6 mice to clarify the immunomodulatory effects of the drug
      on macrophages of C57BL/6, strain mice that is biased to Th1 response. Peritoneal
      macrophages were in vitro treated with miltefosine and phagocytosis of sensitized
      or nonsensitized Saccharomyces cerevisiae was assessed. NO production was
      evaluated by Griess reaction. In the concentration of 1.6 MUg/mL and 50.0 MUg/mL,
      miltefosine increased phagocytosis of non-opsonized S. cerevisiae in 59.7% and
      214.3%, respectively. For phagocytosis through opsonin receptors, miltefosine
      (50.0 MUg/mL) increased the phagocytic index in 208.6% (p=0.04, paired t test).
      Miltefosine (50.0 MUg/mL) decreased in 39.3% NO production by macrophages.
      However, treatment with miltefosine (50.0 MUg/mL) after infection of macrophages
      with Leishmania amazonensis increased NO production in 73.4% (p=0.01, Wilcoxon
      test). Our data showed that, besides the antimicrobial effect of miltefosine, the
      drug showed immunomodulatory effects on macrophages of C57BL/6 mice, improving
      phagocytosis and decreasing NO production, but was able to increase NO production
      when macrophages were previously infected with L. amazonensis. These results
      suggest that miltefosine may favor the better evolution of infectious diseases by
      improving the innate immune response of macrophages.

PMID- 22465962
TI  - Protective effects of a novel trimerized sTNFRII on acute liver injury.
AB  - TNF alpha plays a central role in the pathogenesis of inflammatory diseases such
      as rheumatoid arthritis and murine acute liver injury induced by injection of D
      galactosamine and subsequent LPS. Recombinant Fc-fused soluble TNF receptor II
      (sTNFRII-Fc) has been used in the treatment of rheumatoid arthritis for a decade.
      We have recently constructed a novel fusion protein sTNFRII-gAD, which is
      composed of a soluble TNF receptor II and a globular domain of adiponectin.
      Utilizing the inclination of gAD to form homologous trimer naturally, we sought
      to explore TNFalpha antagonism of the novel trimerized sTNFRII-gAD and meantime
      compare TNFalpha-neutralizing effects in vitro and in vivo between sTNFRII-Fc and
      sTNFRII-gAD. Here, we evaluated the TNFalpha-antagonizing activity of sTNFRII-gAD
      with TNFalpha-induced L929 cytotoxicity assay. Furthermore, sTNFRII-Fc or sTNFRII
      gAD was administered simultaneously with d-galactosamine 1h prior to LPS
      injection in the murine model of acute liver injury. Serum TNFalpha and TNFalpha
      sTNFRII-gAD complex were measured by ELISA and the liver injury was assessed
      through alanine transaminase measurement and liver histological analysis. sTNFRII
      gAD was shown to have higher TNFalpha-neutralizing activity than sTNFRII-Fc
      (p<0.05) in the L929 cytotoxicity assay. With a significant attenuation of murine
      lethality (p<0.05), sTNFRII-gAD showed more protective effects than sTNFRII-Fc in
      the murine model of acute liver injury. These results demonstrated that sTNFRII
      gAD was more efficacious than sTNFRII-Fc as a TNFalpha antagonist, highlighting
      the potential of sTNFRII-gAD for the treatment of diseases associated with
      excessive TNFalpha.

PMID- 22465963
TI  - IL-17A-producing NK cells were implicated in liver injury induced by ischemia and
      reperfusion.
AB  - NK cells play a critical role in several types of liver injury. The aim of this
      study was to evaluate the role of NK cells in liver ischemia reperfusion injury
      (IRI) and the underlying mechanism. Male Rag1-/- mice and wild type mice were
      subjected to partial hepatic IRI. Anti-NK1.1 (300 MUg/mouse, ip) was used to
      deplete NK cells. Liver injury was evaluated by level of serum alanine
      aminotransferase (ALT). Hepatic inflammatory cytokines, neutrophils and CXCL-2
      expression were measured following ischemia and reperfusion. Additionally, NK
      cells were cultured with or without IL-6, IL-21, IL-23 and IL-10 for 24h, then IL
      17A level in the supernatants was analyzed by ELISA. Production of IL-17A was
      increased in NK cells after reperfusion. Various cytokines such as, IL-6, IL-21
      and IL-23, which also elevated after IRI, can promote IL-17A production and up
      regulate the phosphorylation of STAT3 in NK cells, while the increase was
      repressed in the presence of IL-10. Depletion of NK cells decreased IL-17A level
      in Rag1-/- mice ischemic lobes. Meanwhile, hepatic infiltration of neutrophils
      and CXCL-2 level were reduced and liver injury was ameliorated. Neutralization of
      IL-17A was used to confirm the role of this cytokine produced by NK cells in Rag1
      /- mice. In conclusion, at initial stage of liver IRI, NK cells increase IL-17A
      production and promote liver injury.

PMID- 22465964
TI  - Protective role of calcium ion against stress-induced osmotic fragility of red
      blood cells in patients with type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus can increase osmotic fragility of red blood cells.
      Osmotic fragility test is an index of the function of cytoskeletal proteins and
      of the calcium pump activity in RBC membrane. The aim of this study is to
      determine the effect of physiological calcium supplement on red blood cell
      osmotic fragility of patients with type 2 diabetes mellitus. Osmotic fragility of
      red cells was determined for 30 healthy subjects and 30 patients in a NaCl
      gradient medium. 5 mg/dl of calcium was added to media and the osmotic fragility
      were evaluated for RBCs of patients and healthy subjects. Comparison of patients
      and control group showed higher sensitivity of red cells of patients to osmotic
      fragility upon exposure to higher sodium chloride concentrations. Comparison of
      initial, fifty percent and total hemolysis showed significant difference on
      initial and fifty percent hemolysis between two groups (P < 0.001). In healthy
      subjects, Fifty percent hemolysis index showed a smaller change after addition of
      calcium, from 4.1 +/- 0.22 to 3.9 +/- 0.2 (P < 0.05). Fifty percent hemolysis
      index for patients significantly decreased from 4.45 +/- 0.17 to 4 +/- 0.17 after
      addition of calcium (P < 0.001). Osmotic fragility increases in patients with
      diabetes. The role of calcium in cell membrane integrity was more prominent in
      the patients with diabetes than the healthy subjects, emphasizing the role of
      calcium on the membrane stability. We showed for the first time that controlling
      calcium ion concentration in patients with diabetes could exert a protective and
      beneficial role against membrane-affecting conditions.

PMID- 22465965
TI  - Quasi 3D imaging of DNA-gold nanoparticle tetrahedral structures.
AB  - Verification by imaging of the structure of 3D DNA constructs, both bare and
      conjugated to metal nanoparticles, is challenging. We demonstrate here two
      transmission electron microscopy (TEM) based methods to distinguish between fully
      formed tetrahedra, synthesized from DNA conjugated with gold nanoparticles (GNPs)
      at their vertices, and structures which are only partially formed. When deposited
      on a surface, fully formed tetrahedra are expected to retain their 3D pyramidal
      structure, while partially formed structures are expected to form a 2D structure.
      The first method by which 3D and 2D structures were distinguished was imaging
      them at different defocusing values. While for 2D structures all the four GNPs
      acquire Fresnel fringes at the same defocusing value, for 3D structures at least
      one particle is at a different plane with respect to the others, and so it
      acquires Fresnel fringes at a different defocusing value. The second method we
      show is imaging of the structures at different angles. While a single TEM image
      gives only a 2D projection of the structure, by combining information achieved
      from imaging at several tilting angles one may verify the structural construct.

PMID- 22465967
TI  - Mechanism of resistance to trastuzumab and molecular sensitization via ADCC
      activation by exogenous expression of HER2-extracellular domain in human cancer
      cells.
AB  - Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic
      efficacy against HER2-positive breast and gastric cancers; however, acquired
      resistance presents a formidable obstacle to long-term tumor responses in the
      majority of patients. Here, we show the mechanism of resistance to trastuzumab in
      HER2-positive human cancer cells and explore the molecular sensitization by
      exogenous expression of HER2-extracellular domain (ECD) in HER2-negative or
      trastuzumab-resistant human cancer cells. We found that long-term exposure to
      trastuzumab induced resistance in HER2-positive cancer cells; HER2 expression was
      downregulated, and antibody-dependent cellular cytotoxicity (ADCC) activity was
      impaired. We next examined the hypothesis that trastuzumab-resistant cells could
      be re-sensitized by the transfer of non-functional HER2-ECD. Exogenous HER2-ECD
      expression induced by the stable transfection of a plasmid vector or infection
      with a replication-deficient adenovirus vector had no apparent effect on the
      signaling pathway, but strongly enhanced ADCC activity in low HER2-expressing or
      trastuzumab-resistant human cancer cells. Our data indicate that restoration of
      HER2-ECD expression sensitizes HER2-negative or HER2-downregulated human cancer
      cells to trastuzumab-mediated ADCC, an outcome that has important implications
      for the treatment of human cancers.

PMID- 22465968
TI  - Improving LASSO performance for Grey Leaf Spot disease resistance prediction
      based on genotypic data by considering all possible two-way SNP interactions.
AB  - Disease resistance prediction using genotypic data has been widely pursued in
      animal as well as plant research, mostly in cases where genotypic data can be
      readily available for a large number of subjects. With the evolution of SNP
      marker genotyping technology and the consequent cost reduction for genotyping
      thousands of SNP markers, significant research effort is being undertaken in the
      statistics and machine learning community to perform efficient analysis of these
      multidimensional datasets. For large plant breeding programs, besides identifying
      biomarkers associated with disease resistance, developing accurate predictive
      models of the phenotype based on the genotype alone is one of the most relevant
      scientific goals, as it allows for efficient selection without having to grow and
      phenotype every individual. While the importance of interactions for
      understanding diseases has been shown in many studies, the majority of the
      existing methods are limited by considering each biomarker as an independent
      variable, completely ignoring complex interactions among biomarkers. In this
      study, logistic regression p-value, Pearson correlation and mutual information
      were calculated for all two-way SNP interactions with respect to the Grey Leaf
      Spot (GLS) disease resistance phenotype. These interactions were subsequently
      ranked based on these measures and the performance of the LASSO algorithm for GLS
      disease resistance prediction was then shown to be maximized by adding the top 10
      000 two-way interactions from the logistic regression p-value based rank. The
      logistic regression p-value based rank also led to an error rate of more than 3
      percentual points lower than not adding any interaction and more than 3.5
      percentual points lower than adding interactions chosen at random.

PMID- 22465970
TI  - Can oral 5-aminosalicylic acid be administered once daily in the treatment of
      mild-to-moderate ulcerative colitis? A meta-analysis of randomized-controlled
      trials.
AB  - OBJECTIVES: Several trials have demonstrated that oral delayed-release mesalamine
      might be administered once daily. We aimed to conduct a meta-analysis to
      investigate this. METHODS: A comprehensive and multiple-source literature search
      was carried out. Only randomized-controlled trials (RCTs) were investigated by
      comparing a once daily-dosing regime with a divided (twice or thrice daily)
      dosing regime of oral delayed-release mesalamine formulations for induction or
      maintenance of remission in patients with mild-to-moderate ulcerative colitis.
      The quality of RCTs was assessed using the Jadad scores. Meta-analysis of pooled
      odds ratios was carried out using Review Manager 5.1. RESULTS: Nine RCTs were
      finally included. With regard to meta-analyses for induction trials, there were
      no significant differences for all comparisons between the once daily and the
      divided groups, including maintenance of just clinical remission (P=0.52) and
      just endoscopic remission (P=0.23), maintenance of combined clinical and
      endoscopic remission (P=0.78), and the overall incidence of adverse events
      (P=0.61). With regard to meta-analyses for maintenance trials, there were also no
      significant differences for all comparisons between once daily and divided
      groups, including maintenance of just clinical remission (P=0.73) and just
      endoscopic remission (P=0.43), maintenance of combined clinical and endoscopic
      remission (P=0.43), the overall incidence of adverse events (P=0.12) as well as
      compliance with the prescribed medication (P=0.34). CONCLUSION: The present work
      showed that oral delayed-release mesalazine administered as a single or a divided
      dose demonstrated a good safety profile, which was well tolerated and effective
      as either maintenance or induction treatment. High clinical and/or endoscopic
      remission rates can be achieved with once-daily dosing.

PMID- 22465969
TI  - Fat infiltration in the lumbar multifidus and erector spinae muscles in subjects
      with sway-back posture.
AB  - AIM: Decreased activity of the lumbar stabilizer muscles has been identified in
      individuals with sway-back posture. Disuse can predispose these muscles to
      atrophy, which is characterized by a reduced cross-sectional area (CSA) and by
      fat infiltration. The aim of this study was to evaluate the amount of fat
      infiltration in the lumbar multifidus and lumbar erector spinae muscles as a sign
      of the muscle atrophy in individuals with sway-back posture, with and without low
      back pain. MATERIALS AND METHODS: Forty-five sedentary individuals between 16 and
      40 years old participated in this study. The sample was divided into three
      groups: symptomatic sway-back (SSBG) (n = 15), asymptomatic sway-back (ASBG) (n =
      15), and control (CG) (n = 15). The individuals were first subjected to
      photographic analysis to classify their postures and were then referred for a
      magnetic resonance imaging (MRI) examination of the lumbar spine. The total
      (TCSA) and functional (FCSA) cross-sectional areas of the lumbar erector spinae
      together with lumbar multifidus and isolated lumbar multifidus muscles were
      measured from L1 to S1. The amount of fat infiltration was estimated as the
      difference between the TCSA and the FCSA. RESULTS: Greater fat deposition was
      observed in the lumbar erector spinae and lumbar multifidus muscles of the
      individuals in the sway-back posture groups than in the control group. Pain may
      have contributed to the difference in the amount of fat observed in the groups
      with the same postural deviation. Similarly, sway-back posture may have
      contributed to the tissue substitution relative to the control group
      independently of low back pain. CONCLUSIONS: The results of this study indicate
      that individuals with sway-back posture may be susceptible to morphological
      changes in their lumbar erector spinae and lumbar multifidus muscles, both due to
      the presence of pain and as a consequence of their habitual posture.

PMID- 22465971
TI  - Incidence and predictors of postpolypectomy bleeding in colorectal polyps larger
      than 10 mm.
AB  - BACKGROUND: It is well-established that the risk of postpolypectomy bleeding
      (PPB) increases with polyp size, but little is known about the factors that
      predict PPB in polyps larger than 10 mm. AIM: The aim of this study is to assess
      the incidence and risk factors for PPB in colorectal polyps larger than 10 mm.
      METHODS: A historical cohort study was carried out in an open access endoscopy
      unit from January 2007 to December 2008. Endoscopic polypectomy was performed in
      1894 (28%) patients. Clinical records of patients with polyps of at least 10 mm
      were reviewed. Data on demographics, comorbidity, polyp-related features, and
      resection technique were collected. The incidence of immediate bleeding (during
      polypectomy) and delayed bleeding (up to 1 month later) was assessed. RESULTS: A
      total of 424 large polyps (median size=12 mm; P25-P75: 10-16 mm) were resected.
      Thirty-five episodes of PPB occurred in 33 (7.8%) polyps, of which 12 (2.8%) were
      delayed. Multivariate logistic regression analysis demonstrated that a polyp size
      of at least 14 mm was the most important predictor of PPB [odds ratio (OR) 3.17,
      95% confidence interval (CI) 1.492-6.751, P=0.003], compared with the presence of
      a villous architecture (OR 2.23, 95% CI 1.056-4.705, P=0.035) or high-grade
      dysplasia (OR 2.96, 95% CI 1.305-6.692, P=0.009). CONCLUSION: In the current
      study, the rate of PPB was almost 8% in polyps larger than 10 mm, occurring in
      most cases during the endoscopic procedure. A polyp of size at least 14 mm was
      the most important predictor for PPB. Prospective studies are needed to determine
      whether preventive endoscopic therapy may reduce PPB in these patients.

PMID- 22465972
TI  - Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated
      extrahepatic autoimmune diseases.
AB  - AIM: To assess the prevalence of concurrent extrahepatic autoimmune diseases in
      patients with autoimmune hepatitis (AIH)/primary biliary cirrhosis (PBC) overlap
      syndrome and applicability of the 'mosaic of autoimmunity' in these patients.
      METHODS: The medical data of 71 AIH/PBC overlap patients were evaluated for
      associated autoimmune diseases. RESULTS: In the study population, 31 (43.6%)
      patients had extrahepatic autoimmune diseases, including autoimmune thyroid
      diseases (13 patients, 18.3%), Sjogren syndrome (six patients, 8.4%), celiac
      disease (three patients, 4.2%), psoriasis (three patients, 4.2%), rheumatoid
      arthritis (three patients, 4.2%), vitiligo (two patients, 2.8%), and systemic
      lupus erythematosus (two patients, 2.8%). Autoimmune hemolytic anemia,
      antiphospholipid syndrome, multiple sclerosis, membranous glomerulonephritis,
      sarcoidosis, systemic sclerosis, and temporal arteritis were identified in one
      patient each (1.4%). A total of 181 autoimmune disease diagnoses were found in
      our patients. Among them, 40 patients (56.4%) had two, 23 (32.3%) had three, and
      eight (11.3%) had four diagnosed autoimmune diseases. CONCLUSION: A large number
      of autoimmune diseases were associated with AIH/PBC overlap patients. Therefore,
      extended screening for existing autoimmune diseases during the routine assessment
      of these patients is recommended. Our study suggests that the concept of 'mosaic
      of autoimmunity' is a valid clinical entity that is applicable to patients with
      AIH/PBC overlap syndrome.

PMID- 22465973
TI  - Unusually aggressive type 1 gastric carcinoid:  a case report with a review of
      the literature.
AB  - Gastric carcinoids are rare tumors of the stomach. Gastric carcinoid type 1 is
      associated with chronic atrophic gastritis, and because of a low metastatic
      potential, is the most benign type. Death from metastatic disease has been
      reported in only three patients in a review including 724 cases. The present
      report refers to a 60-year-old man who was affected by type 2 diabetes mellitus
      and pernicious anemia and died from metastatic gastric carcinoid type 1. In 1998,
      a well-differentiated 1.2 cm gastric neuroendocrine tumor, immunoreactive for
      chromogranin A, with a Ki-67 index less than 2% and with infiltration to the
      submucosal layer was diagnosed and enucleated. In 2002, a new well-differentiated
      gastric endocrine tumor 6 mm in size with a Ki-67 of approximately 2% was
      detected, and endoscopic ultrasound confirmed it to be limited to the submucosal
      layer. The patient refused antrectomy and started long-acting somatostatin analog
      (lanreotide) in 2005 when the Ki-67 index was 7%, but he stopped the treatment
      after 4 months. In 2007, despite previous endoscopic stability, endoscopic
      ultrasound showed an infiltrating gastric lesion of 7 cm. At surgery, the disease
      appeared to be extended to the liver and to the peritoneum (well-differentiated
      endocrine carcinoma, Ki-67 40%) with both hepatic and massive peritoneal
      metastases. A regimen of somatostatin analog was soon restarted; however, the
      disease continued to spread, and the patient died 6 months later. Overall,
      despite their generally benign course, type 1 gastric carcinoids may have
      malignant potential, a finding that should be considered when planning the
      medical workup of these patients.

PMID- 22465974
TI  - Rearrangement from the heteroantiaromatic borole to the heteroaromatic azaborine
      motif.
AB  - Treatment of 9-chloro-9-borafluorene with N,O-bis(trimethylsilyl)hydroxylamine
      results in 10-trimethylsilyloxy-9-aza-10-boraphenanthrene 6b. NMR spectroscopy
      shows that the expected antiaromatic 9-(trimethylsilyloxyamino)-9-borafluorene 5b
      rearranges to the formally aromatic phenanthrene 6b at room temperature.

PMID- 22465975
TI  - Hepatic GVHD leading to cirrhosis after allogeneic hematopoietic SCT.

PMID- 22465976
TI  - Chronic GVHD is associated with lower relapse risk irrespective of stem cell
      source among patients receiving transplantation from unrelated donors.
AB  - Chronic GVHD (cGVHD) has been associated with reduced risk of relapse after allo
      SCT for onco-hematological disease due to a graft-vs-malignancy effect. Here we
      retrospectively analyzed a series of 802 adult patients transplanted from
      unrelated donors and found that cGVHD was associated with significantly lower
      relapse and that the limited form was associated with a survival advantage:
      hazard ratio for OS=0.63 (0.46-0.87); P=0.004; this was due to combination of
      relapse reduction and similar non-relapse mortality with respect to patients
      without cGVHD. Importantly, the graft-vs-malignancy effect observed here did not
      differ when PBSC or BM were used as stem cell source, thus suggesting that the
      protective effect of limited cGVHD is similar after PBSC- or BM-based
      transplantation. These findings could have practical implications and suggest no
      qualitative difference between cGVHD occurring after transplantation performed
      with different stem cell sources.

PMID- 22465977
TI  - Clinical outcomes of patients with desmoplastic small round cell tumor of the
      peritoneum undergoing autologous HCT: a CIBMTR retrospective analysis.
AB  - Desmoplastic small round cell tumor of the peritoneum (DSRCTP) is a rare,
      frequently fatal tumor. This retrospective study, based on CIBMTR registry data,
      describes the largest reported cohort of DSRCTP patients who have undergone Auto
      SCT. The probabilities of disease-free survival (DFS) at 1 year for patients in
      CR and not in CR were 75% (95% confidence interval: 48-94%) and 35% (15-59%),
      respectively. The probability of OS at 3 years was 57% (29-83%) and 28% (9-51%)
      for patients in CR and not in CR, respectively. Median survival for the entire
      cohort was 31 months (36 months and 21 months for those in CR and not in CR,
      respectively). Engraftment at 42 days was 97% (88-100%). Treatment-related
      mortality was low, with only one death in the first 100 days. Auto-SCT is a
      tolerable approach in patients with DSRCTP, with the greatest benefit seen in
      those patients who obtain CR. For those not in CR, the median OS in this series
      is greater than previously reported (21 months vs 17 months), suggesting Auto-SCT
      is useful in prolonging DFS and OS, even in patients with residual or persistent
      disease pre-transplant.

PMID- 22465978
TI  - Exploring the potential of biobeds for the depuration of pesticide-contaminated
      wastewaters from the citrus production chain: laboratory, column and field
      studies.
AB  - The high wastewater volumes produced during citrus production at pre- and post
      harvest level presents serious pesticide point-source pollution for groundwater
      bodies. Biobeds are used for preventing such point-source pollution occurring at
      farm level. We explored the potential of biobeds for the depuration of
      wastewaters produced through the citrus production chain following a lab-to-field
      experimentation. The dissipation of pesticides used pre- or post-harvest was
      studied in compost-based biomixtures, soil, and a straw-soil mixture. A
      biomixture of composted grape seeds and skins (GSS-1) showed the highest
      dissipation capacity. In subsequent column studies, GSS-1 restricted pesticides
      leaching even at the highest water load (462 Lm(-3)). Ortho-phenylphenol was the
      most mobile compound. Studies in an on-farm biobed filled with GSS-1 showed that
      pesticides were fully retained and partially or fully dissipated. Overall biobeds
      could be a valuable solution for the depuration of wastewaters produced at pre-
      and post-harvest level by citrus fruit industries.

PMID- 22465979
TI  - Suggestions from the field for return to sports participation following anterior
      cruciate ligament reconstruction: American football.
AB  - Returning an American football player to sport after an anterior cruciate
      ligament reconstruction is challenging on several fronts. First, there are
      approximately 15 different positions a football player could play, depending on
      how specifically you define the positions on the field. Each of these positions
      has specific demands for optimal size, strength, power, body composition,
      cardiovascular fitness, and movement. Understanding all of these factors is
      paramount to returning a football player not only to his sport but also to his
      specific position. Second, the chaotic, contact-rich nature of the sport requires
      that heavy demands be placed on the lower extremities to attenuate external
      contact forces from other players and from ground reaction forces associated with
      accelerating, decelerating, quick stops and starts, and changing direction.
      Finally, return to a competitive level of performance is further influenced by
      playing surface, shoe selection, the equipment the player wears, and various
      potential psychosocial factors. It is the responsibility of the clinician to
      provide a progressive and systematic rehabilitation program by first introducing
      preprogrammed movements that, once mastered, are progressed with elements of more
      reactive and random movement patterns. The precise nature of this systematic
      progression of advanced rehabilitation is key in developing return-to-play
      criteria and, ultimately, in readying an American football player for eventual
      return to sport and a particular position.

PMID- 22465980
TI  - Gene expression profiling of nephrotoxicity from copper nanoparticles in rats
      after repeated oral administration.
AB  - The goal of this study was to investigate the mechanisms of nanocopper-induced
      nephrotoxicity by analyzing renal gene expression profiles phenotypically
      anchored to conventional toxicological outcomes. Male Wistar rats were given
      nanocopper (50, 100, 200 mg/kg) and microcopper (200 mg/kg) at different doses
      for 5 days. We found nanocopper can induce widespread renal proximal tubule
      necrosis in rat kidneys with blood urea nitrogen and creatinine increase. Whole
      genome transcriptome profiling of rat kidneys revealed significant alterations in
      the expression of many genes involved in valine, leucine, and isoleucine
      degradation, complement and coagulation cascades, oxidative phosphorylation, cell
      cycle, mitogen-activated protein kinase signaling pathway, glutathione
      metabolism, and others may be involved in the development of these phenotypes.
      Results from this study provide new insights into the nephrotoxicity of copper
      nano-particles and illustrate how toxicogenomic approaches are providing an
      unprecedented amount of mechanistic information on molecular responses to
      nanocopper and how they are likely to impact hazard and risk assessment.

PMID- 22465981
TI  - Neuroprotective effects of phlorotannins isolated from a brown alga, Ecklonia
      cava, against H2O2-induced oxidative stress in murine hippocampal HT22 cells.
AB  - Exposure of neurons to hydrogen peroxide (H(2)O(2)) results in oxidative stress
      and the activation of a cascade of intracellular toxic events resulting in
      oxidation, lipid peroxidation, and Ca(2+) elevation, ultimately resulting in cell
      death. In this study, we attempted to characterize the neuroprotective effects of
      phlorotannins isolated from Ecklonia cava, including phloroglucinol, eckol,
      triphloroethol A, eckstolonol, and dieckol, against H(2)O(2)-induced cell damage
      in murine hippocampus neuronal (HT22) cells. We measured the reactive oxygen
      species (ROS) and lipid peroxidation levels and evaluated the resultant cell
      death and alterations in Ca(2+)-concentrations. All phlorotannins were to
      scavenge intracellular ROS and repress ROS accumulation, thus preventing lipid
      peroxidation. Consquently, all phlorotannins reduced H(2)O(2)-induced cell death
      in HT22 cells. Moreover, phlorotannins inhibited H(2)O(2)-induced Ca(2+) release.
      This study provides a new useful strategy for preventing neuronal H(2)O(2)
      induced oxidative stress.

PMID- 22465982
TI  - Ultrasonic evaluation of acute impact injury of articular cartilage in vitro.
AB  - OBJECTIVE: The aim of the study was to investigate whether high frequency
      ultrasound technique, originally designed for arthroscopic use can be utilized to
      detect traumatic cartilage injuries. METHODS: A total of four intact
      osteochondral plugs were prepared from eight patellas for parallel comparison
      (total of 32 plugs). The plugs were injured by dropping an impactor on them from
      heights of 2.5 cm, 5.0 cm, 10.0 cm and 15.0 cm (corresponding to impact energies
      of 0.12, 0.25 0.50 and 0.74 J, respectively), in a custom made dropping tower.
      The samples were imaged with a high frequency (40 MHz) ultrasound device before
      and after the injury. Reflection coefficient (R), integrated reflection
      coefficient (IRC), apparent integrated backscattering (AIB) and ultrasound
      roughness index (URI) were determined for each sample. RESULTS: Injuries
      invisible to the naked eye could be sensitively detected via the decreased values
      of the ultrasound reflection parameters (P < 0.05). Furthermore, a decreasing
      trend was detected in the values of R and IRC as the momentum of the impactor
      increased. The values of AIB were significantly lower for samples injured by
      dropping the impactor on the cartilage from heights of 2.5 cm and 15 cm but the
      URI values were similar in intact and injured cartilage. Histological analysis of
      the cartilage samples revealed that the injured cartilage exhibited depletion of
      the cartilage surface proteoglycans but the structure of collagen network was
      almost normal. CONCLUSIONS: Quantitative ultrasound imaging enables the detection
      of minor visually non-detectable cartilage injuries. As the present technique is
      feasible for arthroscopic use it might have clinical value in the evaluation of
      cartilage lesions during arthroscopy e.g., after tear of the anterior cruciate
      ligament.

PMID- 22465983
TI  - Efficacy of semiquantitatively measured serum procalcitonin as a guide to
      cessation of antibiotic therapy in septic patients.

PMID- 22465984
TI  - Early adaptations to eccentric and high-velocity training on strength and
      functional performance in community-dwelling older adults.
AB  - The authors examined whether an eccentric training program or a high-velocity
      training program was more beneficial in regards to function and strength.
      Nineteen community-dwelling older adults, between the ages of 65 and 89 years,
      from a local senior center participated in the 8-week exercise program. All
      participants were randomly assigned to either an eccentric or a high-velocity
      training group. A doubly multivariate analysis of variance with 1 between
      subjects factor and repeated measures was used to examine group and time
      differences. This analysis revealed that no differences existed between the
      groups (p > 0.05). However, there were within-group differences for both the high
      velocity and the eccentric groups. For both groups, walking speed, 8-ft up-and-go
      time, chair stand, leg extension strength, leg curl strength, and leg press
      strength increased from preintervention to postintervention (p < 0.05). This
      suggests that a high-velocity training program provides similar results as an
      eccentric training program but with less total work. The eccentric training group
      trained at a higher percentage of their 1RM and tested with higher loads, which
      may suggest that a longer exercise program would show the eccentric training
      group to be stronger and more functional. Fitness practitioners dealing with an
      older adult population should focus on training with all types of training
      velocities. Not only are these types of training modalities safe for this
      population but they also can improve their ability to perform activities of daily
      living.

PMID- 22465985
TI  - A training program to improve neuromuscular and performance indices in female
      high school soccer players.
AB  - The purpose of this study was to determine if a sports-specific anterior cruciate
      ligament injury prevention training program could improve neuromuscular and
      performance indices in female high school soccer players. We combined components
      from a published knee ligament intervention program for jump and strength
      training with other exercises and drills to improve speed, agility, overall
      strength, and aerobic fitness. We hypothesized that this program would
      significantly improve neuromuscular and athletic performance indices in high
      school female soccer players. The supervised 6-week program was done 3 d.wk(-1)
      for 90-120 minutes per session on the soccer fields and weight room facilities in
      area high schools. In phase 1, 62 athletes underwent a video drop-jump test, t
      test, 2 vertical jump tests, and a 37-m sprint test before and upon completion of
      the training program. In phase 2, 62 other athletes underwent a multistage
      fitness test before and after training. There were significant improvements in
      the mean absolute knee separation distance (p < 0.0001), mean absolute ankle
      separation distance (p < 0.0001), and mean normalized knee separation distance (p
      < 0.0001) on the drop-jump, indicating a more neutral lower limb alignment on
      landing. Significant improvements were found in the t-test (p < 0.0001),
      estimated maximal aerobic power (p < 0.0001), 37-m sprint test (p = 0.02), and in
      the 2-step approach vertical jump test (p = 0.04). This is the first study we are
      aware of that demonstrated the effectiveness of a knee ligament injury prevention
      training program in improving athletic performance indices in high school female
      soccer players. Future studies will determine if these findings improve athlete
      compliance and team participation in knee ligament injury intervention training.

PMID- 22465986
TI  - Running speeds at ventilatory threshold and maximal oxygen consumption
      discriminate futsal competitive level.
AB  - We tested the hypothesis that maximal oxygen uptake and ventilatory threshold
      (VT), and their respective speeds (S(VO2max) and S(VT)) could discriminate the
      competitive level of futsal players. The outfield players of a high-level
      Brazilian professional futsal team (N = 9; age 22.6 +/- 4.2 years; body mass 70.6
      +/- 6.4 kg; height 174.3 +/- 6.0 cm), and a semiprofessional team (N = 11; age
      17.2 +/- 0.8 years; body mass 70.4 +/- 6.5 kg; height 175.0 +/- 4.0 cm),
      volunteered for participation in this study. Subsequently, they were evaluated
      during an incremental treadmill test for the determination of cardiorespiratory
      variables, S(VO2max), and S(VT). Both teams exhibited a similar body mass and
      VO2max (p = 0.542 and p = 0.427), whereas the S(VO2max) and the S(VT) were
      significantly higher in the professional team (p = 0.001 and p = 0.030,
      respectively). Additionally, the professional team exhibited both lower HR at VT
      (p = 0.046) and HRmax (p = 0.002). However, the %HRmax at VT did not differ
      between groups (p = 0.912). These results remained similar after adjusting for
      the age differences between groups (p = 0.106). It was concluded that both
      S(VO2max) and S(VT) were sensitive for detecting differences in the competitive
      level of futsal players, whereas VO2max and VT were not.

PMID- 22465987
TI  - A comparison of heart rate response and frequencies of technical actions between
      half-court and full-court 3-a-side games in high school female basketball
      players.
AB  - The purpose of this study was to compare heart rate (HR) response and frequency
      of technical actions between half-court and full-court 3-a-side games in female
      high school basketball players. Twelve young female basketball players (age 15.5
      +/- 0.5 years; height 165.1 +/- 5.7 cm; body mass 57.3 +/- 7.2 kg; training age
      4.2 +/- 0.7 years; HRmax 202.9 +/- 5.6 b.min(-1)) participated in this study
      voluntarily. On the first day, anthropometric measurements (height and body mass)
      were taken for each player; this was followed by the Yo-Yo intermittent recovery
      test (YIRT) level 1 for the subjects. Then, half-court and full-court 3-a-side
      games were organized in random order at 2-day intervals. The HRmax for each
      player was determined during the YIRT, after which the HR was measured during the
      3-a-side games. In addition, the frequencies of different categories of technical
      actions were counted manually during the 3-a-side games. A paired t-test was
      calculated for each dependent variable, including HR, percentage of maximum HR
      (%HRmax), and the frequencies of different technical actions to compare half
      court and full-court 3-a-side games. The study results indicate that the full
      court 3-a-side games produced significantly higher responses than the half-court
      3-a-side games in terms of HR and %HRmax (p < 0.05), whereas the half-court games
      resulted in significantly higher frequencies of technical actions (p < 0.05). The
      results of this study suggest that, if coaches want to achieve greater HR
      responses, coaches of female high school basketball players should organize full
      court 3-a-side games, whereas coaches who want to focus on technical actions
      should arrange half-court 3-a-side games.

PMID- 22465988
TI  - Effects of compression on muscle tissue oxygenation at the onset of exercise.
AB  - The effects of compression on gastrocnemius medialis muscle oxygenation and
      hemodynamics during a short-term dynamic exercise was investigated in a sample of
      15 male subjects (mean +/- SD; age 25.8 +/- 4.9 years; mass 70.6 +/- 4.3 kg).
      Elastic compression sleeves were used to apply multiple levels of compression to
      the calf muscles during exercise, and noncompressive garments were used for the
      control condition. Tissue hemoglobin oxygen saturation was measured as the
      relative "tissue oxygen index" (TOI) with a near-infrared spectrometer. The
      recovery of TOI during exercise was determined from the slope of oxygenation
      recovery in a nonoccluded situation. The TOI recovery rate during the first 2
      minutes of the exercise was 24% higher (p = 0.042) for the compression condition
      than for the control condition. A significant correlation (r = 0.61, p = 0.012)
      between the level of compression and the tissue oxygenation recovery during
      exercise was observed. Muscle energy use was determined from the rate of decline
      of TOI immediately upon arterial occlusion during early exercise. Muscle energy
      use measured during the occluded situation was not significantly influenced by
      compression. Based on these results, it was concluded that compression induced
      changes in tissue blood flow and perfusion appear to result in improved
      oxygenation during short-term exercise. Assuming that increased muscle oxygen
      availability positively influences performance, compression of muscles may
      enhance performance especially in sports that require repeated short bouts of
      exercise.

PMID- 22465989
TI  - Physical characteristics and abilities of junior elite male and female handball
      players.
AB  - This study first aimed to examine strength, speed, and jumping abilities in 29
      male and 29 female junior elite handball players and second to compare Under-18
      and Under-16 players in the selected parameters. The players were chosen by the
      Norwegian Handball Federation, and all were tested in strength (squat and bench
      press), speed (10-, 30-, and 6 * 30-m repeated sprint ability), and jumping
      abilities (countermovement jump and squat jump [SJ]). Anthropometric qualities
      were also measured. Independent t-tests were applied to reveal possible mean
      differences between the U-18 and U-16 players within each sex. No significant
      differences in anthropometry were observed between the U18 and U16 players within
      either sex. Furthermore, we did not observe any significant between group
      differences among the male players in any of the tested performance parameters.
      On average, however, the U16 male (n = 14) players performed better in all the
      tests compared with in the U18 (n = 15) male players. Similarly, we did not find
      any significant differences in test performances between U18 female players and
      U16 female players. Still, a few trends (p <= 0.1) were observed because female
      U18 (n = 14) players were found to sprint faster on both 10 and 30 m and to jump
      higher in SJ vs. female U16 (n = 15) players. The empirical findings do not
      confirm the hypothesis of pubertal development and muscle growth leading to
      taller and heavier U18 players. Furthermore, we expected U18 players to perform
      better in all the tests when compared with U16 players. Again, the data did not
      substantiate this, although female U18 players tended to perform better in sprint
      and SJ compared with the U16 players.

PMID- 22465990
TI  - A novel method of anaerobic performance assessment in swimming.
AB  - The purpose of this study was to develop a novel, anaerobic efficiency test in
      swimming. The concept of this test was build upon the classic Wingate anaerobic
      test, with the difference that the dependent variables are extracted from an
      instantaneous speed curve. Twelve highly trained male swimmers, 19.3 (+/-3.3)
      years of age, 1.84 (+/-0.08) m in height, and 77 (+/-12.8) kg in weight,
      participated in the study. The swimmers swam a 100-m race in a 25-m pool,
      following the instructions to attain maximal swimming speed as quickly as
      possible and to keep maximal speed as long as possible. The race was recorded by
      means of video cameras (50 samples per second). Raw data were filtered by means
      of standard mathematical functions: smoothing and a polynomial function fit. The
      following speed parameters: maximal speed (Vmax), time to reach Vmax
      (tVmax(reach)), time at Vmax (tVmax(keep)), minimal speed (Vmin), and fatigue
      index were extracted from the filtered speed curve. Thorough assessment of
      anaerobic performance in swimming requires a swimming test leading to development
      of a speed curve obtained during a maximal effort race and not race time alone.

PMID- 22465991
TI  - No kinetic differences during variations of the power clean in inexperienced
      female collegiate athletes.
AB  - Previous research has identified that the second pull phase of the clean
      generates the greatest power output and that the midthigh variations of the power
      clean also result in the greatest force and power output in male athletes;
      however, no research has compared the kinetics of the variations of the power
      clean in women. The aim of this investigation was to identify any differences
      between variations of the clean, across a range of loads, in inexperienced female
      collegiate athletes. Sixteen healthy female collegiate athletes (age 19 +/- 2.3
      years; height 166.5 +/- 3.22 cm; body mass 62.25 +/- 4.52 kg; 1 repetition
      maximum [1RM] power clean 51.5 +/- 2.65 kg) performed 3 repetitions of 3
      variations (power clean, hang power clean, midthigh power clean) of the power
      clean at 60, 70, and 80% of their predetermined 1RM power clean, in a randomized
      and counterbalanced order. A 2-way analysis of variance (3 * 3; load * variation)
      revealed no significant differences (p > 0.05) in peak power, peak vertical force
      (Fz) or rate of force development (RFD) between loads or variations of the power
      clean. There appears to be no advantage in terms of peak power, Fz, or RFD
      between variations of the clean, in inexperienced female athletes, it is
      suggested, therefore, that inexperienced athletes intermittently perform
      different variations of the clean to ensure all round development and technical
      competence in each variation of the exercise.

PMID- 22465992
TI  - Relationship between indicators of training load in soccer players.
AB  - This study examined the relationship between work load indicators used to
      quantify full training sessions in soccer. The participants were 28
      semiprofessional male soccer players age 22.9 +/- 4.2 years, height 177 +/- 5 cm,
      body mass 73.6 +/- 4.4 kg. Players' physical and physiological work load was
      monitored over 44 training sessions using global positioning system devices (10
      Hz) and heart rate, respectively. After each training session, players' training
      perceived-exertion (rating of perceived exertion [RPE]) was assessed using the
      Borg CR-10 scale. Players' internal training load was assessed using the session
      RPE and the Edwards methods. Total distance, distances covered at arbitrary
      selected high-intensity speed zones (>=18 and 21 km.h(-1)), bout frequency at
      speed >18 and 21 km.h(-1), and work:rest ratio during training drills were
      considered as signs of physical work load. Furthermore, player load assumed as
      reflection of total center-of-mass acceleration was considered as representative
      of players' external load. Very-large association of player load with Edwards and
      session-RPE methods was found. Total distance covered was large to very large
      associated with Player Load, Session-RPE, and Edwards methods. The findings of
      this study provided evidence for the safe use of session-RPE, Edwards methods,
      and Players Load as valid indicators of training responses in soccer.

PMID- 22465994
TI  - Mode of delivery in non-cephalic presenting twins: a systematic review.
AB  - PURPOSE: This systematic review aims to determine if there are evidence-based
      recommendations for the optimal mode of delivery for non-cephalic presenting
      first- and/or second twins. We investigated the impact of the mode of delivery on
      neonatal outcome for twin deliveries with (1) the first twin (twin A) in non
      cephalic presentation, (2) the second (twin B) in non-cephalic presentation and
      (3) both twins in non-cephalic presentation. METHODS: A computer-aided search of
      Medline, Embase, Cinahl and Cochrane databases was carried out and quality of the
      studies was assessed with the Cochrane Collaboration's tool for assessing risk of
      bias and the GRADE approach. RESULTS: One high-quality clinical trial (60 twin
      pairs) and 16 moderate/low-quality observational studies (3,167 twin pairs)
      showed no difference in neonatal outcome between vaginal and caesarean delivery
      in twin A and/or B. CONCLUSION: Our results do not suggest benefit of caesarean
      over vaginal delivery for selected twin gestations with twin A and/or twin B in
      non-cephalic presentation. However, no final conclusion can be drawn due to the
      small sample sizes and statistic limitations of the included studies. Randomized
      studies with sufficient power are required to make a strong recommendation.

PMID- 22465995
TI  - Deterioration of endothelial function and carotid intima-media thickness in
      Tibetan male adolescents exposed to second-hand smoke.
AB  - INTRODUCTION: It has been commonly accepted that second-hand smoke (SHS) is
      associated with atherosclerosis and endothelial dysfunction. There is growing
      evidence that the changes might begin in childhood. Unfortunately, no study has
      focused on the early atherosclerosis of Tibetan adolescents exposed to SHS. AIMS:
      We aimed to investigate the endothelial function and carotid atherosclerosis in
      healthy school-aged Tibetan male adolescents. MATERIALS AND METHODS: All passive
      smoking participants (SHS) were students were 16 years old and male, and were
      recruited through middle schools in Lhasa city. In total 624 subjects were
      accepted after excluding subjects who actively smoked. The adolescents were
      divided into three groups according to serum cotinine level: high cotinine group
      (High Group) with 205 boys, intermediate cotinine group (Intermediate Group) with
      210 boys, and low cotinine group (Low Group) with 209 boys. Venous blood was
      sampled for the measurement of cotinine concentration, lipid profile and
      endothelin-1 (ET-1) quantitation. High-resolution B-mode ultrasonography was
      performed to evaluate carotid intima-media thickness (cIMT) and intima
      smoothness. The invasive vascular endothelial function was evaluated through the
      measurement of flow-mediated dilation (FMD) with B-mode ultrasound and ankle
      brachial index (ABI) by using a blood pressure cuff and a Doppler instrument.
      RESULTS: No statistical significance was found between groups in total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, triglyceride, ApoA-I, systolic blood pressure, diastolic blood
      pressure, and heart rate (p>0.05). In the lipid profile, only apolipoprotein B
      (ApoB) values were different between groups: ApoB in the High Group was higher
      than in the Low Group (p=0.0164). Plasma ET-1 concentrations in the High Group
      were also much higher than in the Intermediate and Low Groups (p=0.0112,
      p<0.001). The cIMT and intima smoothness had deteriorated in the High Group
      compared with the Low Group (p<0.001 and p<0.05 respectively). FMD and ABI, which
      indicate vascular endothelial function, was decreased in the High Group compared
      with the Intermediate and Low Groups (FMD, p<0.001; ABI, p<0.001). CONCLUSIONS:
      SHS was associated with sub-clinical carotid atherosclerosis and endothelial
      dysfunction in Tibetan school-aged male adolescents. Considering the widespread
      exposure to SHS and the clinical relevance of early atherosclerosis, this result
      is of public health importance in Tibet, where health education is not
      satisfactory. Data from our study emphasize the importance of endorsing smoke
      free environments for adolescents.

PMID- 22465997
TI  - Acoustofluidics 11: Affinity specific extraction and sample decomplexing using
      continuous flow acoustophoresis.
AB  - Acoustic standing wave technology combined with ligand complexed microbeads
      offers a means for affinity specific selection of target analytes from complex
      samples. When realized in a microfluidic format we can capitalize on laminar flow
      and acoustic forces that can drive cells or microbeads across fluid interfaces.
      Given this, we have the ability to perform carrier fluid (suspending medium)
      exchange operations in continuous flow in microfluidic chips based solely on
      acoustofluidic properties. A key issue here is to ensure that a minimum of the
      original carrier fluid follows the cells/particles across the fluid interface.
      Simple processing protocols can be achieved that may outperform macroscale
      magnetic bead-based sample extraction or centrifugation steps, which can also be
      straightforwardly integrated with downstream analytical instrumentation. This
      tutorial outlines some basic fluidic configurations for acoustophoresis based
      sample decomplexing and details the different system parameters that will impact
      the outcome of an acoustophoresis based affinity extraction experiment or a cell
      medium exchange step. Examples are given of both targeted extraction of microbes
      and selective elusion of molecular species.

PMID- 22465996
TI  - Nkx3.1 functions as para-transcription factor to regulate gene expression and
      cell proliferation in non-cell autonomous manner.
AB  - Nkx3.1 is a homeoprotein transcription factor (TF) that inhibits proliferation of
      prostate epithelial cells (PECs) and acts as a tumor suppressor for prostate
      cancer (PCa). Because TFs classically function within the cells that produce
      them, Nkx3.1-induced growth inhibition was considered to occur in a cell
      autonomous manner. We, however, found that Nkx3.1 protein can be secreted from
      cultured PECs and is detectable in the prostatic fluid and urine. A PCa-related
      point mutation (T164A) abolished Nkx3.1 secretion. Amazingly, secreted Nkx3.1
      protein can translocate into adjacent cells, bind to the regulatory sequence of
      Nkx3.1 target genes and impact the expression of these genes in these adjacent
      cells. Expression of Nkx3.1 in PECs can also affect gene expression in adjacent
      cells, and this effect is abolished by the T164A mutation. Nkx3.1 protein
      inhibits cell proliferation when added to the culture. Expression of Nkx3.1, not
      the T164A mutant, also inhibits the proliferation of co-cultured cells. These
      results indicate that Nkx3.1 functions as a "para-transcription factor (PTF),"
      with the ability to regulate genes and inhibit cell proliferation in a non-cell
      autonomous manner. We also demonstrate that Nkx3.1 contains an evolutionarily
      conserved protein transduction domain essential for its PTF function, implicating
      potentially common PTF function among homeoproteins. In addition to the PCa
      related T164A mutant, the secreted Nkx3.1 is reduced drastically in the prostatic
      fluid and urine of mice with PCa. These results indicate that Nkx3.1 can function
      as a PTF to suppress PCa and the urinary Nkx3.1 may be a potential biomarker for
      PCa diagnosis.

PMID- 22465998
TI  - Computed tomography angiography evaluation of internal carotid artery free
      floating thrombus--single-center diagnosis, false-positives, and follow-up.

PMID- 22465999
TI  - Replication study to confirm the role of CYP2D6 polymorphism rs1080985 on
      donepezil efficacy in Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder often treated with
      donepezil, an acetylcholinesterase inhibitor. Response to donepezil is variable,
      probably based on patients' genetic background in donepezil metabolizing enzymes,
      including cytochrome 2D6 (CYP2D6). We evaluated the association between clinical
      response to donepezil and a common variant (rs1080985) of CYP2D6, previously
      reported to be associated with poor response to the drug. In a sample of 415 AD
      cases, we found evidence of association between rs1080985 and response to
      donepezil after 6 months of therapy (OR [95% CI]: 1.74 [1.01-3.00], p = 0.04).
      Rs1080985 might be useful as predictor of poor response to short-term donepezil
      treatment.

PMID- 22466000
TI  - Aging-related neurostructural, neuropathological, and behavioral changes
      associated with herpes simplex virus type 1 brain infection in mice.
AB  - To date, the main advances in understanding Alzheimer's disease (AD) have
      revolved around the genetic variants associated with the familial form of the
      disease, yet the majority of cases are sporadic. The main risk factor for AD is
      aging, followed by production of the E4 isoform of apolipoprotein E (APOE).
      Female gender also increases the risk of developing AD. Herpes simplex virus type
      1 (HSV-1) has been epidemiologically and experimentally associated with AD,
      although no studies on its effects over aging have been undertaken. To assess the
      potential aging-related consequences of HSV-1 brain infection, 2 month-old wild
      type and apoE-deficient mice were infected with the virus, and over the next 16
      months analyses made of cerebral viral load, neuropathological, morphological,
      and metabolic changes in the brain, and cognitive performance. Viral load in the
      central nervous system (CNS) increased with age. The viral load in the brains of
      aged apoE+/+ female mice was 43 times that seen in apoE-/- male mice. No MRI
      detectable morphological differences nor any clear neuropathological differences
      were seen between 18 month-old infected and mock-infected mice, although
      differences were seen in younger animals. Neuroinfection was associated with
      memory deficit and a reduction in metabolic indicators of CNS health.

PMID- 22466001
TI  - Relationship between cognitive domains, physical performance, and gait in elderly
      and demented subjects.
AB  - Cognitive function declines with age, with studies linking decreases in cognitive
      function to increased fall risk. The association between declines in specific
      cognitive domains and the development of gait and physical performance deficits
      has not been established. The current cross-sectional study was designed to
      address these issues using well characterized control subjects (n = 50), and
      individuals with early stage dementia (n = 50) tightly matched for age, gender,
      and education. All participants received detailed cognitive assessments for
      global cognitive function, as well as for processing speed, verbal fluency, and
      executive function. Additionally, participants were administered single- and dual
      task gait assessments (GAITRite) and Short Physical Performance Battery (SPPB)
      measures of physical performance (gait, balance, chair stands). Data show that
      all measures of cognitive function correlated significantly with measures of gait
      and physical performance when analyzed in all subjects or just subjects with
      dementia. However, data also reveal that measures of processing speed and verbal
      fluency correlated significantly with multiple aspects of motor performance in
      non-demented, control subjects, even when corrected for age. There was no
      correlation between global cognitive function and motor performance, and only
      limited relationship between executive function and motor performance in non
      demented, control subjects. These studies reveal the complex interactions between
      cognitive function and gait/physical performance in the context of aging and
      dementia, and suggest that impairments in specific cognitive domains might
      undermine gait and physical performance and thus exacerbate fall risk in the
      elderly.

PMID- 22466002
TI  - Changes in brain transcripts related to Alzheimer's disease in a model of HFE
      hemochromatosis are not consistent with increased Alzheimer's disease risk.
AB  - Iron abnormalities are observed in the brains of Alzheimer's disease (AD)
      patients, but it is unclear whether common disorders of systemic iron overload
      such as hemochromatosis alter risks of AD. We used microarrays and real-time
      reverse transcription-PCR to investigate changes in the brain transcriptome of
      adult Hfe-/- mice, a model of hemochromatosis, relative to age- and gender
      matched wildtype controls. Classification by functional pathway analysis revealed
      transcript changes for various genes important in AD. There were decreases of up
      to 9-fold in transcripts for amyloid-beta protein precursor, tau, apolipoprotein
      E, presenilin 1, and various other gamma-secretase components, as well as Notch
      signaling pathway molecules. This included decreased transcripts for 'hairy and
      enhancer of split' Hes1 and Hes5, downstream targets of Notch canonical
      signaling. The reductions in Hes1 and Hes5 transcripts provide evidence that the
      changes in levels of transcripts for gamma-secretase components and Notch
      signaling genes have functional consequences. The effects appeared relatively
      specific for AD in that few genes pertaining to other important neurodegenerative
      diseases, notably Parkinson's disease and Huntington's disease, or to
      inflammation, oxidative stress, or apoptosis, showed altered transcript levels.
      The observed effects on AD-related gene transcripts do not appear to be
      consistent with increased AD risk in HFE hemochromatosis and might, if anything,
      be predicted to protect against AD to some extent. As Hfe-/- mice did not have
      higher brain iron levels than wildtype controls, these studies highlight the need
      for further research in models of more severe hemochromatosis with brain iron
      loading.

PMID- 22466003
TI  - Cortical thickness in frontotemporal dementia, mild cognitive impairment, and
      Alzheimer's disease.
AB  - Cortical thickness analysis has been proposed as a potential diagnostic measure
      in memory disorders. In this retrospective study, we compared the cortical
      thickness values of 24 patients with frontotemporal dementia (FTD) to those of 25
      healthy controls, 45 symptomatic subjects with stable mild cognitive impairment
      (S-MCI), 15 subjects with progressive mild cognitive impairment (P-MCI), and 36
      patients with Alzheimer's disease (AD). The patterns of regions of thinning in
      FTD when compared to controls and also S-MCI patients showed similar trends;
      thinning of the bilateral frontal poles and bilateral medial temporal lobe
      structures, especially the anterior part of the gingulum, the uncus, and
      parahippocampal gyri. Cortical thinning in FTD was also found on the boundary
      regions of parietal and occipital lobes. In the P-MCI group compared to FTD, the
      trend of thinning in small distinct areas of the parietal and occipital lobes was
      observed. The FTD and AD groups did not differ statistically, but we found trends
      toward thinning in FTD of the left cingulate gyrus, and the left occipitotemporal
      gyri, and in AD of the inferior parietal, occipitoparietal, and the pericalcarine
      regions, more in the right hemisphere. In FTD, increased slowness in the
      executive test (Trail-Making A) correlated with the thinner cortex, whereas the
      language tests showed the lower scores, the thinner cortex in the left
      hemisphere. Cortical thickness might be a tool for detecting subtle changes in
      brain atrophy in screening of dementia prior to the development of diffuse or
      lobar atrophies.

PMID- 22466004
TI  - Mitochondrial dysfunction and immune activation are detectable in early
      Alzheimer's disease blood.
AB  - Alzheimer's disease (AD), like other dementias, is characterized by progressive
      neuronal loss and neuroinflammation in the brain. The peripheral leukocyte
      response occurring alongside these brain changes has not been extensively
      studied, but might inform therapeutic approaches and provide relevant disease
      biomarkers. Using microarrays, we assessed blood gene expression alterations
      occurring in people with AD and those with mild cognitive changes at increased
      risk of developing AD. Of the 2,908 differentially expressed probes identified
      between the three groups (p < 0.01), a quarter were altered in blood from mild
      cognitive impairment (MCI) and AD subjects, relative to controls, suggesting a
      peripheral response to pathology may occur very early. There was strong evidence
      for mitochondrial dysfunction with decreased expression of many of the
      respiratory complex I-V genes and subunits of the core mitochondrial ribosome
      complex. This mirrors changes previously observed in AD brain. A number of genes
      encoding cell adhesion molecules were increased, along with other immune-related
      genes. These changes are consistent with leukocyte activation and their increased
      the transition from circulation into the brain. In addition to expression
      changes, we also found increased numbers of basophils in people with MCI and AD,
      and increased monocytes in people with an AD diagnosis. Taken together this study
      provides both an insight into the functional response of circulating leukocytes
      during neurodegeneration and also identifies potential targets such as the
      respiratory chain for designing and monitoring future therapeutic interventions
      using blood.

PMID- 22466005
TI  - TLR3-dependent immune regulatory functions of human mesangial cells.
AB  - In glomerulonephritis, the migration of inflammatory cells into the glomerulus is
      an important step in disease initiation and progression. The viral receptor Toll
      like receptor 3 (TLR3) is known to play a role in virus-associated
      glomerulonephritis. Based on this knowledge, this study aimed to define the
      effects of the TLR3 ligand polyriboinosinic:polyribocytidylic acid (poly(I:C)) on
      the expression of adhesion molecules and macrophage colony-stimulating factor (M
      CSF) on resident glomerular cells. Experiments in MCs demonstrated that the
      activation of viral receptors by poly(I:C) leads to a time- and dose-dependent
      induction of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion
      molecule 1 (VCAM-1) and M-CSF at both the mRNA and protein levels; these results
      were confirmed by incubating MCs with HCV RNA. As shown in knockdown experiments,
      this effect is specifically mediated by TLR3. The prestimulation of MCs with
      proinflammatory cytokines increases the effects of poly(I:C), except for its
      induction of VCAM-1. Tumor-necrosis factor (TNF)-alpha, likewise, induces ICAM-1,
      VCAM-1 and M-CSF, and amplifies the mesangial response to poly(I:C). These
      results were confirmed by incubating MCs with HCV RNA. We thus provide evidence
      that human MCs represent a potential target of the leukocytes and monocytes that
      infiltrate the glomerulus in viral disease-associated GN, highlighting the
      possibility that MCs may act as resident antigen-presenting cells.

PMID- 22466006
TI  - UASB performance and microbial adaptation during a transition from mesophilic to
      thermophilic treatment of palm oil mill effluent.
AB  - The treatment of palm oil mill effluent (POME) by an upflow anaerobic sludge bed
      (UASB) at organic loading rates (OLR) between 2.2 and 9.5 g COD l(-1) day(-1) was
      achieved by acclimatizing the mesophilic (37  degrees C) microbial seed to the
      thermophilic temperature (57  degrees C) by a series of stepwise temperature
      shifts. The UASB produced up to 13.2 l biogas d(-1) with methane content on an
      average of 76%. The COD removal efficiency ranged between 76 and 86%. Microbial
      diversity of granules from the UASB reactor was also investigated. The PCR-based
      DGGE analysis showed that the bacterial population profiles significantly changed
      with the temperature transition from mesophilic to thermophilic conditions. In
      addition, the results suggested that even though the thermophilic temperature of
      57  degrees C was suitable for a number of hydrolytic, acidogenic and acetogenic
      bacteria, it may not be suitable for some Methanosaeta species acclimatized from
      37  degrees C. Specifically, the bands associated with Methanosaeta thermophila
      PT and Methanosaeta harundinacea can be detected during the four consecutive
      operation phases of 37  degrees C, 42  degrees C, 47  degrees C and 52  degrees
      C, but their corresponding bands were found to fade out at 57  degrees C. The
      DGGE analysis predicted that the temperature transition can result in significant
      methanogenic biomass washout at 57  degrees C.

PMID- 22466007
TI  - Bilateral changes in forearm oxygen consumption at rest and after exercise in
      patients with unilateral repetitive strain injury: a case-control study.
AB  - STUDY DESIGN: Case-control study. OBJECTIVES: To investigate whether oxygen
      consumption and blood flow at rest and after exercise are lower in the affected
      arm of patients with repetitive strain injury (RSI) compared to controls, and
      lower in the healthy nonaffected forearm within patients with unilateral RSI.
      BACKGROUND: RSI is considered an upper extremity overuse injury. Despite the
      local presentation of complaints, RSI may be represented by systemic adaptations.
      Insight into the pathophysiology of RSI is important to better understand the
      development of RSI complaints and to develop effective treatment and prevention
      strategies. METHODS: Twenty patients with unilateral RSI and 20 gender-matched
      control subjects participated in this study. Forearm muscle blood flow and oxygen
      consumption were measured using near-infrared spectroscopy at baseline and
      immediately after isometric handgrip exercises at 10%, 20%, and 40% of the
      individual maximal voluntary contraction. RESULTS: Unilateral RSI resulted in a
      lower oxygen consumption and blood flow in the affected forearm at baseline and
      lower oxygen consumption after incremental handgrip exercises compared to
      controls (P<.05). In addition, exercise-induced blood flow and oxygen consumption
      in the nonaffected forearm in patients with RSI were similarly reduced.
      CONCLUSION: Blood flow and oxygen consumption after exercise are similarly
      attenuated in the affected and nonaffected arms of patients with unilateral RSI.
      Our findings suggest that, despite the unilateral character in clinical symptoms,
      RSI demonstrates systemic adaptations in forearm blood flow and oxygen
      consumption at rest and after exercise.

PMID- 22466008
TI  - Effects of cytosine methylation on DNA charge transport.
AB  - The methylation of cytosine bases in DNA commonly takes place in the human genome
      and its abnormality can be used as a biomarker in the diagnosis of genetic
      diseases. In this paper we explore the effects of cytosine methylation on the
      conductance of DNA. Although the methyl group is a small chemical modification,
      and has a van der Waals radius of only 2 A, its presence significantly changes
      the duplex stability, and as such may also affect the conductance properties of
      DNA. To determine if charge transport through the DNA stack is sensitive to this
      important biological modification we perform multiple conductance measurements on
      a methylated DNA molecule with an alternating G:C sequence and its non-methylated
      counterpart. From these studies we find a measurable difference in the
      conductance between the two types of molecules, and demonstrate that this
      difference is statistically significant. The conductance values of these
      molecules are also compared with a similar sequence that has been previously
      studied to help elucidate the charge transport mechanisms involved in direct DNA
      conductance measurements.

PMID- 22466009
TI  - Design for risk control: the role of usability engineering in the management of
      use-related risks.
AB  - The majority of medical device incident reports can primarily be attributed to
      use error. Greater attention to human factors and usability during development of
      a medical device could improve this situation. However, recent studies have shown
      that companies do not find the application of a sound usability engineering
      process according to international standards a simple task. The purpose of this
      collaborative research project between a medical device company, two universities
      and a university hospital was to study the practical application of the
      International Standard for Application of Usability Engineering to Medical
      Devices, IEC 62366, by means of a case study in industrial practice. This paper
      describes the user studies in the case and reveals the factors important to
      success. Also, the paper demonstrates how to apply an iterative usability
      engineering process within a linear product development process in industry.
      Management support and careful planning of resources and activities proved
      essential. To control use-related risks, the usability engineer should 'design
      for risk control' in a structured manner, while the risk manager should remain
      responsible for acceptable levels of residual risk. The paper concludes with
      recommendations for the improvement of IEC 62366 and ISO 14971, the standard for
      the risk management of medical devices.

PMID- 22466010
TI  - A phantom assessment of portable imaging and radio-guided surgery systems with
      technetium-99m and fluorine-18.
AB  - AIM: To perform a detailed analysis of the performance of mobile intraoperative
      imaging systems and gamma probes in a phantom set-up, and compare this with a
      conventional gamma camera. METHODS: Two separate experiments were performed. In
      the first, a modified Jaszczak phantom equipped with five (99m)Tc-filled hot
      spheres (0.5-20 ml) was analyzed using Sentinella, declipseSPECT and a
      conventional gamma camera under three conditions: no background, spheres on the
      surface of the background activity, and totally immersed spheres (contrast level
      in both 1: 8). In the second experiment, two phantom spheres (0.5 and 2 ml)
      filled with (99m)Tc and (18)F (infinite contrast, 1: 4 and 1: 8) were measured
      using the hand-held probes Navigator and GammaLocator DXI. Data analysis
      consisted of signal-to-background ratios and determination of the full-width at
      half-maximum (FWHM). A visual scoring was performed by three nuclear medicine
      physicians. RESULTS: At infinite contrast, (99m)Tc-filled spheres with volumes of
      at least 2 ml could be detected adequately with all systems (e.g. 2 ml sphere,
      FWHM: ECAM 11 mm, declipseSPECT 9 mm, Navigator 13 mm, GammaLocator 12 mm). Under
      decreased contrast conditions, the results for all systems were impaired and the
      0.5 ml phantom sphere filled with either (99m)Tc or (18)F was only detected
      accurately by the GammaLocator (FWHM range: 13-17 mm). CONCLUSION: All systems
      are suitable for intraoperative sentinel node detection with nearly infinite
      signal-to-background contrast. At a lower contrast, the GammaLocator performed
      best for the detection of small volumes at low-contrast ratios regardless of the
      radionuclide.

PMID- 22466011
TI  - Incremental prognostic value of 99mTc-tetrofosmin early poststress pulmonary
      uptake. Determination of the optimal cut-off value.
AB  - OBJECTIVES: To evaluate the incremental prognostic value of (99m)Tc-tetrofosmin
      early poststress lung/heart ratio (eLHR) and to assess the optimal cut-off value.
      MATERIALS AND METHODS: We studied 503 patients (aged 61.3 years/SD = 8.6 years,
      302 men) with stress/rest (99m)Tc-tetrofosmin myocardial gated-single photon
      emission computed tomography and coronary angiography. To evaluate myocardial
      ischemia, the summed stress score, summed rest score, and summed difference score
      indices were calculated. For the eLHR calculation, an anterior image was acquired
      4-6 min after radiotracer injection at stress; eLHR was defined as the mean
      counts/pixel in the lung region of interest divided by the mean counts/pixel in
      the myocardial region of interest. The incremental prognostic value of eLHR was
      evaluated by a significant increase in the global chi(2) of the Cox proportional
      hazard model that included clinical, exercise, angiographic, and scintigraphic
      variables. Using the receiver operating characteristic analysis, the optimal cut
      off of eLHR for the prediction of cardiac events was determined. RESULTS: During
      the follow-up period, hard cardiac events occurred in 50 (9.9%) and soft cardiac
      events in 61 (12.1%) patients. Receiver operating characteristic curve analysis
      showed that the optimal cut-off of eLHR for the prediction of cardiac events was
      0.51, with a sensitivity of 78.4% and specificity of 72.2%. The area under the
      curve was 0.82 (95% confidence interval: 0.77-0.87). Multiple Cox regression
      analysis revealed that eLHR more than 0.51 (hazard ratio = 7.78; 95% confidence
      interval: 5.00-12.11) provided incremental prognostic value over clinical
      exercise testing and scintigraphic data for cardiac events. CONCLUSION: A (99m)Tc
      tetrofosmin eLHR value larger than 0.51 added incremental value to other
      variables for the prediction of cardiac events.

PMID- 22466013
TI  - Solid Eu(III) complexes studied by positron annihilation, optical and Mossbauer
      spectroscopies: insights on the positronium formation mechanism.
AB  - In this work, positron annihilation lifetime (PALS), Doppler broadening
      annihilation radiation lineshape (DBARL), Mossbauer and optical spectroscopies
      measurements were performed in Eu(III) dipivaloylmetanate complex, Eu(dpm)(3), at
      295 and 80 K. The Eu(dpm)(3) complex is not luminescent at 298 K and does not
      form positronium. On the other hand, it is highly luminescent at 80K, but still
      does not form positronium. The absence of positronium formation at 80K cannot be
      explained by a ligand/metal charge transfer process. We found strong evidences
      that the electronic delocalization does not occur at both temperatures. Despite
      the Mossbauer results being inconclusive regarding the Eu(III)/Eu(II) reduction
      hypothesis, previous results showing positronium formation in other Eu(III)
      complexes suggest that this process is not occurring. Thus, more studies are
      needed to explain the absence of positronium in Eu(III) complexes.

PMID- 22466014
TI  - The effects of low-intensity pulsed ultrasound on tendon-bone healing in a
      transosseous-equivalent sheep rotator cuff model.
AB  - PURPOSE: The purpose of this study was to examine the effects Low-intensity
      Pulsed Ultrasound has on initial tendon-bone healing in a clinically relevant
      extra-articular transosseous-equivalent ovine rotator cuff model. METHODS: Eight
      skeletally mature wethers, randomly allocated to either control group (n = 4) or
      treatment group (n = 4), underwent rotator cuff surgery following injury to the
      infraspinatus tendon. All animals were killed 28 days post surgery to allow
      examination of early effects of Low-intensity Pulsed Ultrasound treatment.
      RESULTS: General improvement in histological appearance of tendon-bone
      integration was noted in the treatment group. Newly formed woven bone with
      increased osteoblast activity along the bone surface was evident. A continuum was
      observed between the tendon and bone in an interdigitated fashion with Sharpey's
      fibres noted in the treatment group. Low-intensity Pulsed Ultrasound treatment
      also increased bone mineral density at the tendon-bone interface (p < 0.01),
      while immunohistochemistry results revealed an increase in the protein expression
      patterns of VEGF (p = 0.038), RUNX2 (p = 0.02) and Smad4 (p = 0.05). CONCLUSIONS:
      The results of this study indicate that Low-intensity Pulsed Ultrasound may aid
      in the initial phase of tendon-bone healing process in patients who have
      undergone rotator cuff repair. This treatment may also be beneficial following
      other types of reconstructive surgeries involving the tendon-bone interface.

PMID- 22466015
TI  - Faster recovery after minimally invasive surgery in total knee arthroplasty.
AB  - PURPOSE: The aim of the study was to identify whether less soft tissue and muscle
      damage during surgery will allow faster recovery after total knee arthroplasty in
      comparison with the conventional technique. A limited medial parapatellar
      approach without tibial medial collateral ligament (MCL) desinsertion was
      compared with the conventional parapatellar approach. METHODS: Three hundred
      patients were randomized either into the minimally invasive group (MIS group) or
      into the conventional group (CON group). The evaluation was based on the Knee
      Society Score, range of motion, blood loss, period of hospitalization and
      postoperative hemoglobin level. RESULTS: The MIS group showed faster recovery
      with immediate postoperative full weight-bearing and shorter length of stay (5 vs
      10 days). Comparable Knee Society Scores (87.5 vs 88), function scores (90) and
      alignment (5.5 degrees  vs 5.2 degrees ) between the CON and MIS group were
      observed at a follow-up of 24 months. No increase in operative times (52 vs 51
      min tourniquet time) or no complications were observed. Reduced blood loss was
      observed in the MIS group (590 vs 989 ml). CONCLUSION: The MCL sparing limited
      medial parapatellar approach allows good surgical exposure, easy extension
      proximally if necessary, contained closure after surgery with less bleeding,
      faster recovery, full weight-bearing without aid and most importantly no
      radiological malalignment. LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 22466016
TI  - Complications in endonasal sinus surgery: a 5-year retrospective study of 2,596
      patients.
AB  - Recent developments should have aided to reduce postoperative complications of
      endoscopic sinonasal surgery: Computerised tomography (CT) and magnetic resonance
      imaging (MRI) allow a more precise preoperative view of the anatomic situation
      and possible variations. The Lund-MacKay-Index provides a tool to assess the
      extent of the disease, and by introducing microscopic-endonasal and computer
      assisted sinunasal surgery (CAS) as well as providing the corresponding training
      technical progress has been made. We analysed the data of 2,596 patients with
      acute or chronic rhinosinusitis who underwent surgery between 2000 and 2005 using
      the procedure of Stammberger. We saw 3.1 % minor complications (minor bleedings,
      perforation of the lamina papyracea), 0.9 % major complications (severe
      bleedings, cerebrospinal fluid (CSF) leaks, lesion of the ductus lacrimalis), and
      one (0.04 %) serious complication (meningitis). When we compared these figures
      with those of reports from the late 90 s by correlating opacification, type of
      operation, the surgeon's experience and employing CAS with the outcome we did not
      find a distinct improvement in the rate of postoperative complications. Serious
      complications and those resulting in permanent harm such as carotid artery
      injury, cerebral deficit or death have, however, become very rare. A grading into
      I (minor), II (major) and III (serious) complications is proposed, to point out
      this critical grade-III proportion, which should not exceed 0.1 %.

PMID- 22466018
TI  - Femoral neck fractures in Lithuania and Sweden. The differences in care and
      outcome.
AB  - PURPOSE: Hip fractures constitute a serious and common health problem from both
      individual and public health perspectives. Unified data collection and comparison
      between countries is recognised as an effective tool for care improvements.
      However, the variation in patients' demography, treatment methods and other local
      cultural aspects in different countries should be considered. The aim of our
      study was to compare femoral neck fracture patients treated in Kaunas and Lund,
      concerning functional outcome and quality of life. METHODS: We investigated 99
      patients treated by arthroplasty in Kaunas Clinics and 117 patients in Lund
      University Hospital. Patients were investigated according to the National Swedish
      Hip Fracture Register model and were followed up for a period of four months
      after the injury. The patient's place of residence, mobility, complaints of pain
      and additional hospital stay were recorded. The EQ-5D questionnaire was used to
      evaluate quality of life. RESULTS: Patients in Kaunas were significantly younger,
      had lower ASA grade and were more mobile before trauma and at four moths follow
      up. However, when comparing quality of life at four months follow-up between the
      institutions, Lund patients reported significantly better self care, felt less
      pain and discomfort, and had less symptoms of anxiety and depression.
      CONCLUSIONS: The difference observed in quality of life rating between
      institutions might be related to local cultures of the countries and should be
      considered when comparing the data.

PMID- 22466019
TI  - 4-Nonylphenol and bisphenol A in Swedish food and exposure in Swedish nursing
      women.
AB  - 4-Nonylphenol (NP) and bisphenol A (BPA) are phenolic substances used in high
      volumes by the industry. Studies on cells and in experimental animals have shown
      that both these compounds can be classified as estrogenic hormone disrupters.
      Information about the exposure of humans to NP and BPA is still scarce,
      especially regarding levels in human blood. The first aim of this study was to
      investigate possible sources of NP and BPA exposure from food, by analyzing the
      levels of NP and BPA from a Swedish food market basket, based on the Swedish per
      capita food consumption. A second aim was to investigate blood serum levels of NP
      and BPA, as well as NP-ethoxylates, among young women in Sweden (n=100).
      Moreover, associations between food consumption and blood NP and BPA levels were
      studied. In food, NP was to some extent found at levels above limit of
      quantification (LOQ 20 ng/g fresh weight) in fruits, cereal products, vegetables,
      and potatoes. BPA levels above LOQ (2 ng/g fresh weight) were found in fish,
      meats, potatoes, and dairy products. The estimated mean intakes per capita were
      (medium bound) 27 MUg NP/day and 3.9 MUg BPA/day, showing that food is a source
      of BPA and NP in the general Swedish population. In blood serum, free NP above
      limit of detection (LOD 0.5 ng/g) was detected in 46% of the study participants
      while detectable levels of total NP (LOD 0.8 ng/g) were observed in 43%. The
      corresponding percentages for BPA were 25% and 22%, respectively. The results
      indicate that there is a continuous source of exposure to NP and BPA that is high
      enough for free NP and BPA to be detected in some consumers. Among the
      participants with quantifiable levels of free and total NP (n=38), 85% (median,
      range: 38-112%) of the NP was present as free NP. For BPA 76% (49-109%) was
      detected as free BPA (n=15). All women had levels of ethoxylates of NP below LOD
      (0.1-0.7 ng/g). A significantly higher total consumption of fruits and vegetables
      was reported in questionnaires by participants with NP levels at or above LOD
      than among women with levels below LOD. This result is supporting the market
      basket results of relatively high NP levels in these types of food.

PMID- 22466021
TI  - Chronic neck pain and treatment of cognitive and behavioural factors: results of
      a randomised controlled clinical trial.
AB  - PURPOSE: Although there is growing evidence in favour of the bio-psychosocial
      approach to the treatment of persistent neck pain, it is questioned whether
      treating psychological factors can improve patient perceptions of disability,
      pain and quality of life. This randomised, controlled study with 12 months'
      follow-up was conducted to evaluate the efficacy of adding cognitive-behavioural
      principles to exercises for chronic neck pain. METHODS: Eighty patients were
      randomly assigned to the usual neck exercises plus cognitive-behavioural
      treatment (PTcb group, 40 subjects) or to treatment based on neck exercises alone
      (PT group, 40 subjects). Before treatment (T1), at the end of treatment (T2) and
      12 months later (T3), all of the patients completed a booklet including the Neck
      Pain and Disability Scale, a numerical rating scale, and the Short-Form Health
      Survey Questionnaire (SF-36). RESULTS: The present trial failed to demonstrate
      its primary end point: the pre- and post-treatment difference in total NPDS
      scores was not statistically different between groups. Disability improved
      similarly in both groups over time, remaining stable until T3 in the PTcb group
      and slightly increasing at the same time in the PT group. Pain trends were
      comparable, with both groups showing an improvement between T1 and T2, and a
      slight worsening between T2 and T3. There were significant increases in all of
      the SF-36 domains except for health in general, and vitality in both groups by
      the end of treatment. SF-36 showed a between-group difference only for the
      physical activity domain (10.4; 95% CI 2.4-18.5). CONCLUSION: Disability, pain
      and quality of life improved at the end of treatment in both groups, without
      differences between them.

PMID- 22466020
TI  - Expression dynamics of metabolic and regulatory components across stages of
      panicle and seed development in indica rice.
AB  - Carefully analyzed expression profiles can serve as a valuable reference for
      deciphering gene functions. We exploited the potential of whole genome
      microarrays to measure the spatial and temporal expression profiles of rice genes
      in 19 stages of vegetative and reproductive development. We could verify
      expression of 22,980 genes in at least one of the tissues. Differential
      expression analysis with respect to five vegetative tissues and preceding stages
      of development revealed reproductive stage-preferential/-specific genes. By using
      subtractive logic, we identified 354 and 456 genes expressing specifically during
      panicle and seed development, respectively. The metabolic/hormonal pathways and
      transcription factor families playing key role in reproductive development were
      elucidated after overlaying the expression data on the public databases and
      manually curated list of transcription factors, respectively. During floral
      meristem differentiation (P1) and male meiosis (P3), the genes involved in
      jasmonic acid and phenylpropanoid biosynthesis were significantly upregulated. P6
      stage of panicle, containing mature gametophytes, exhibited enrichment of
      transcripts involved in homogalacturonon degradation. Genes regulating auxin
      biosynthesis were induced during early seed development. We validated the stage
      specificity of regulatory regions of three panicle-specific genes, OsAGO3,
      OsSub42, and RTS, and an early seed-specific gene, XYH, in transgenic rice. The
      data generated here provides a snapshot of the underlying complexity of the gene
      networks regulating rice reproductive development.

PMID- 22466022
TI  - Attention training to reduce attention bias and social stressor reactivity: an
      attempt to replicate and extend previous findings.
AB  - Cognitive theories suggest that social anxiety is maintained, in part, by an
      attentional bias toward threat. Recent research shows that a single-session of
      attention modification training (AMP) reduces attention bias and vulnerability to
      a social stressor (Amir, Weber, Beard, Bomyea, & Taylor, 2008). In addition,
      exercise may augment the effects of attention training by its direct effects on
      attentional control and inhibition, thereby allowing participants receiving the
      AMP to more effectively disengage attention from the threatening cues and shift
      attention to the neutral cues. We attempted to replicate and extend previous
      findings by randomizing participants (N = 112) to a single-session of: a)
      Exercise + attention training (EX + AMP); b) Rest + attention training (REST +
      AMP); c) Exercise + attention control condition (EX + ACC); or d) Rest +
      attention control condition (REST + ACC) prior to completing a public speaking
      challenge. We used identical assessment and training procedures to those employed
      by Amir et al. (2008). Results showed there was no effect of attention training
      on attention bias or anxiety reactivity to the speech challenge and no
      interactive effects of attention training and exercise on attention bias or
      anxiety reactivity to the speech challenge. The failure to replicate previous
      findings is discussed.

PMID- 22466023
TI  - Haven't we met somewhere before? The effects of a brief Internet introduction on
      social anxiety in a subsequent face to face interaction.
AB  - Social anxiety occurs in a range of social situations, the salience of which is
      influenced by prevailing modes of social contact. The emergence of computer
      mediated communication (CMC), buoyed by the recent explosion of social networks,
      has changed the way many people make and maintain social contacts. We randomly
      assigned 30 socially anxious and 30 low social anxiety participants to a brief
      internet chat introduction or a control internet surfing condition followed by a
      standardized face to face (FTF) interaction. We hypothesized that for socially
      anxious participants the chat introduction would reduce anxiety of and preference
      to avoid the subsequent FTF interaction. Results supported hypotheses for most
      indices. Findings suggest that, at least for the common situation in which
      internet chat precedes FTF interaction with the same person, such contact may
      reduce social anxiety. It is not known whether this decrease would generalize to
      FTF contact in other contexts. It is suggested that CMC might be construed as a
      particularly useful form of safety behavior that may help in the allocation of
      attentional resources to process new information relevant for disconfirmation of
      negative beliefs maintaining social anxiety. Potential clinical implications are
      discussed.

PMID- 22466024
TI  - Instituting parent education practices in the neonatal intensive care unit: an
      administrative case report of practice evaluation and statewide action.
AB  - BACKGROUND AND PURPOSE: Infants born preterm are at high risk of developmental
      disabilities and benefit from early developmental intervention programs. Physical
      therapists with neonatal expertise are ideally suited to educate parents about
      ways to support their infant's development in the first months of life. However,
      administrative policies are needed to support the therapist in providing adequate
      parent education in the neonatal intensive care unit (NICU). This administrative
      case report describes the process used by a team of neonatal therapists to
      evaluate clinical practice, determine the need for change, and develop and
      implement a new parent education program in the NICU. CASE DESCRIPTION: Physical
      therapy parent education practices were evaluated in an academic medical center
      with a 36-bed, level-3 NICU. Physical therapists with neonatal expertise covered
      multiple units within the hospital each day. A series of focus groups, a small
      descriptive study, and staff discussion were used to evaluate parent education
      practices in this academic medical center. A new parent education program was
      developed based on data collected and literature to improve clinical care.
      OUTCOMES: The new parent education model was implemented over the course of
      several months using overlapping initiatives. Administrative support for the
      change was developed through collaboration, open communication, and presentation
      of clinical data. In addition, this hospital-based program contributed to the
      development of a statewide initiative to educate parents of preterm infants about
      the importance of supporting development in the first months of life. DISCUSSION:
      A collaborative and data-driven approach to evaluating parent education practices
      supported the development of a new parent education practice while acknowledging
      the need to meet staff productivity standards and provide excellent care
      throughout the hospital.

PMID- 22466025
TI  - Feasibility, reliability, and agreement of the WeeFIM instrument in Dutch
      children with burns.
AB  - BACKGROUND: Burns occur frequently in young children. To date, insufficient data
      are available to fully describe the functional consequences of burns. In
      different patient populations and countries, the WeeFIM instrument ("WeeFIM")
      often is used to measure functional independence in children. OBJECTIVE: The
      purpose of this study was to examine the psychometric properties of the WeeFIM
      instrument for use in Dutch burn centers. DESIGN: This was an observational
      study. METHODS: The WeeFIM instrument was translated into Dutch. All clinicians
      who rated the children with the instrument passed the WeeFIM credentialing
      examination. They scored consecutive children (n=134) aged 6 months to 16 years
      admitted to Dutch burn centers with acute burns during a 1-year period at 2 to 3
      weeks, 3 months, and 6 months postburn. To examine reliability, 2 raters scored a
      child at the same time (n=52, 9 raters) or the same rater scored a child twice
      within 1 week (n=7, 3 raters). RESULTS: After a few weeks, the WeeFIM assessment
      could be administered in less than 15 minutes. Clinicians thought it was
      difficult to rate a child aged between 2 and 4 years as well as the cognitive
      items. Nevertheless, reliability was good (all intraclass correlation
      coefficients [1,1] were above .80). The standard error of measurement was 3.7.
      LIMITATIONS: Intrarater reliability was based on only 7 test-retest measurements.
      Within our clinical setting, it turned out to be difficult to schedule the same
      rater and patient twice in one week for repeated assessments. Assessments for
      interrater reliability, on the other hand, worked out well. CONCLUSIONS: The
      WeeFIM instrument is a feasible and reliable instrument for use in children with
      burns. For evaluation of a child's individual progress, at least 11 points'
      improvement should be observed to state that a child has significantly improved.

PMID- 22466026
TI  - Early intensive postural and movement training advances head control in very
      young infants.
AB  - BACKGROUND: Daily experiences are thought to play an important role in motor
      development during infancy. There are limited studies on the effect of postural
      and movement experiences on head control. OBJECTIVE: The purpose of this study
      was to quantify the effects of postural and movement experiences on head control
      through a comprehensive set of measurements beginning when infants were 1 month
      old. DESIGN: This was a prospective, longitudinal, 2-cohort study. METHODS:
      Twenty-two full-term infants who were healthy were randomly assigned to either a
      training group or a control group. Infants were observed every other week from 1
      to 4 months of age. Head control was assessed using a standardized developmental
      assessment tool, the Test of Infant Motor Performance (TIMP), as well as
      behavioral coding and kinematics of infants' head postures and movements in a
      supported sitting position. Caregivers performed at least 20 minutes of daily
      postural and movement activities (training group), or social interaction (control
      group) for 4 weeks. RESULTS: The training group had higher TIMP scores on head
      control-related items during the training period and after training stopped
      compared with the control group. Starting from the during training phase, the
      training group infants had their heads in a vertical and midline position longer
      compared with the control group infants. After training stopped, the training
      group infants actively moved their heads forward more often and for larger
      distances. LIMITATIONS: The experiences outside daily training were not
      monitored, and the results may be specific to the experimental setup for infants
      with typical development. CONCLUSIONS: Young infants are able to take advantage
      of postural and movement experiences to rapidly advance their head control as
      early as 4 to 6 weeks of postnatal life. Infant positioning, caregiver handling,
      and caregiver-infant interactions were likely contributing factors. This database
      of comprehensive measures may be useful in future trials focused on head control
      in infants with special needs.

PMID- 22466027
TI  - Effects of transcutaneous electrical nerve stimulation on pain, pain sensitivity,
      and function in people with knee osteoarthritis: a randomized controlled trial.
AB  - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is commonly used
      for the management of pain; however, its effects on several pain and function
      measures are unclear. OBJECTIVE: The purpose of this study was to determine the
      effects of high-frequency TENS (HF-TENS) and low-frequency TENS (LF-TENS) on
      several outcome measures (pain at rest, movement-evoked pain, and pain
      sensitivity) in people with knee osteoarthritis. DESIGN: The study was a double
      blind, randomized clinical trial. SETTING: The setting was a tertiary care
      center. PARTICIPANTS: Seventy-five participants with knee osteoarthritis (29 men
      and 46 women; 31-94 years of age) were assessed. INTERVENTION: Participants were
      randomly assigned to receive HF-TENS (100 Hz) (n=25), LF-TENS (4 Hz) (n=25), or
      placebo TENS (n=25) (pulse duration=100 microseconds; intensity=10% below motor
      threshold). MEASUREMENTS: The following measures were assessed before and after a
      single TENS treatment: cutaneous mechanical pain threshold, pressure pain
      threshold (PPT), heat pain threshold, heat temporal summation, Timed "Up & Go"
      Test (TUG), and pain intensity at rest and during the TUG. A linear mixed-model
      analysis of variance was used to compare differences before and after TENS and
      among groups (HF-TENS, LF-TENS, and placebo TENS). RESULTS: Compared with placebo
      TENS, HF-TENS and LF-TENS increased PPT at the knee; HF-TENS also increased PPT
      over the tibialis anterior muscle. There was no effect on the cutaneous
      mechanical pain threshold, heat pain threshold, or heat temporal summation. Pain
      at rest and during the TUG was significantly reduced by HF-TENS, LF-TENS, and
      placebo TENS. LIMITATIONS: This study tested only a single TENS treatment.
      CONCLUSIONS: Both HF-TENS and LF-TENS increased PPT in people with knee
      osteoarthritis; placebo TENS had no significant effect on PPT. Cutaneous pain
      measures were unaffected by TENS. Subjective pain ratings at rest and during
      movement were similarly reduced by active TENS and placebo TENS, suggesting a
      strong placebo component of the effect of TENS.

PMID- 22466028
TI  - Inspiratory muscle strength training in infants with congenital heart disease and
      prolonged mechanical ventilation: a case report.
AB  - BACKGROUND AND PURPOSE: Inspiratory muscle strength training (IMST) has been
      shown to improve maximal pressures and facilitate ventilator weaning in adults
      with prolonged mechanical ventilation (MV). The purposes of this case report are:
      (1) to describe the rationale for IMST in infants with MV dependence and (2) to
      summarize the device modifications used to administer training. CASE DESCRIPTION:
      Two infants with congenital heart disease underwent corrective surgery and were
      referred for inspiratory muscle strength evaluation after repeated weaning
      failures. It was determined that IMST was indicated due to inspiratory muscle
      weakness and a rapid, shallow breathing pattern. In order to accommodate small
      tidal volumes of infants, 2 alternative training modes were devised. For infant
      1, IMST consisted of 15-second inspiratory occlusions. Infant 2 received 10
      breath sets of IMST through a modified positive end-expiratory pressure valve.
      Four daily IMST sets separated by 3 to 5 minutes of rest were administered 5 to 6
      days per week. The infants' IMST tolerance was evaluated by vital signs and daily
      clinical reviews. OUTCOMES: Maximal inspiratory pressure (MIP) and rate of
      pressure development (dP/dt) were the primary outcome measures. Secondary outcome
      measures included the resting breathing pattern and MV weaning. There were no
      adverse events associated with IMST. Infants generated training pressures through
      the adapted devices, with improved MIP, dP/dt, and breathing pattern. Both
      infants weaned from MV to a high-flow nasal cannula, and neither required
      subsequent reintubation during their hospitalization. DISCUSSION: This case
      report describes pediatric adaptations of an IMST technique used to improve
      muscle performance and facilitate weaning in adults. Training was well tolerated
      in 2 infants with postoperative weaning difficulty and inspiratory muscle
      dysfunction. Further systematic examination will be needed to determine whether
      IMST provides a significant performance or weaning benefit.

PMID- 22466029
TI  - Identification of the recently described Cronobacter condimenti by an rpoB-gene
      based PCR system.

PMID- 22466030
TI  - Liver cirrhosis as a predisposing condition for Legionnaires' disease: a report
      of four laboratory-confirmed cases from China.
AB  - Here, we describe four cases of laboratory-confirmed Legionella infection. Case 1
      was a culture-confirmed case of Legionella infection in a patient with liver
      cirrhosis. Following this, three other liver cirrhosis cases (cases 2-4) were
      diagnosed with Legionella infection as confirmed by quantitative real-time PCR.
      The cause of the pneumonia was determined as Legionella pneumophila by positive
      direct fluorescence assay and isolation of the causative agent. The infections
      were successfully treated by administering appropriate antibiotics. These cases
      highlight the importance of considering Legionella as a cause of pneumonia in
      patients with liver disease and lung infections. The strain of L. pneumophila
      isolated from Case 1 was characterized as being closely related to strain
      Philadelphila-1 (ATCC 33152(T)), which is the type strain of the species,
      belonging to serogroup 1 and sequence type 36 (ST36), and is known to be
      distributed worldwide. To our knowledge, this is the first report of Legionella
      infection on the Chinese mainland for a decade and highlights the need to raise
      awareness of diagnostic methods for Legionnaires' disease in China and the
      requirement for further epidemiological surveillance strategies to monitor this
      disease.

PMID- 22466031
TI  - Outbreak of pulmonary infection caused by Klebsiella pneumoniae isolates
      harbouring blaIMP-4 and blaDHA-1 in a neonatal intensive care unit in China.
AB  - Outbreaks caused by Klebsiella pneumoniae producing carbapenemases and other beta
      lactamases have been reported. Four neonates admitted to a neonatal intensive
      care unit (NICU) in a Chinese hospital developed respiratory infection while
      receiving intensive care. In all four cases, multidrug-resistant K. pneumoniae
      was isolated from multiple respiratory specimens, leading to additional
      characterization of these organisms and investigation of the local environment in
      the NICU. Multiple beta-lactamase genes, including bla(TEM-1), bla(IMP-4),
      bla(DHA-1) and bla(CTX-M-14), as well as the quinolone resistance gene qnrB4,
      were harboured by transferable plasmids from all four clinical isolates.
      Furthermore, PFGE confirmed that three of the four clinical isolates from the
      patients and three K. pneumoniae isolates collected from the hands of health-care
      workers and an incubator in the NICU belonged to the same PFGE cluster,
      indicating that an outbreak due to multidrug-resistant K. pneumoniae carrying
      bla(IMP-4) and bla(DHA-1) occurred in this NICU. As far as is known, this is the
      first report of the co-existence of bla(IMP-4) and bla(DHA-1) in the same K.
      pneumoniae isolate. These data suggest that additional precautions are needed to
      prevent outbreaks of infection caused by multidrug-resistant K. pneumoniae
      resulting from environmental exposure in NICUs.

PMID- 22466032
TI  - Identification of porcine rotavirus-like genotype P[6] strains in Taiwanese
      children.
AB  - The molecular characterization of genotype P[6] rotavirus strains collected from
      children admitted to hospital with acute dehydrating diarrhoea during a 6-year
      surveillance period in Taiwan is described in this study. In total, three G4P[6]
      strains, one G5P[6] and one G12P[6] were characterized by sequencing and
      phylogenetic analysis of the VP4, VP7, VP6 and NSP4 genes. Whilst all four genes
      of the single Taiwanese G12P[6] strain clustered with the respective genes of
      globally common human rotavirus strains, the G4 and G5 strains showed remarkable
      similarities to porcine rotavirus strains and putative porcine-origin human P[19]
      strains reported previously from Taiwan. The overall proportion of porcine
      rotavirus-like strains in Taiwan remains around 1 % among hospitalized children;
      however, the circulation and sporadic transmission of these heterotypic strains
      from pigs to humans could pose a public-health concern. Therefore, continuation
      of strain monitoring is needed in the vaccine era to detect any possible vaccine
      breakthrough events associated with the introduction of such heterologous
      rotavirus strains.

PMID- 22466033
TI  - A novel in vivo model to study bacterial pathogenesis and screen potential
      therapeutic targets.

PMID- 22466034
TI  - Incident user cohort study of risk for gastrointestinal bleed and stroke in
      individuals with major depressive disorder treated with antidepressants.
AB  - OBJECTIVE: To examine the association between exposure to newer antidepressants
      and risk of gastrointestinal (GI) and other bleeding complications among
      individuals with major depressive disorder (MDD). DESIGN: This study uses an
      incident user cohort design to compare associations between incidence of
      vascular/bleeding events and the relative affinity (low, moderate or high) of the
      antidepressant for the serotonin transporter during an exposure risk period for
      each patient. SETTING: New England healthcare system electronic medical record
      database. PARTICIPANTS: 36 389 individuals with a diagnosis of MDD and
      monotherapy with a selective serotonin reuptake inhibitor, serotonin
      norepinephrine reuptake inhibitor or other new-generation antidepressant were
      identified from among 3.1 million patients in a New England healthcare system.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Rates of bleeding or other vascular
      complications, including acute liver failure, acute renal failure, asthma, breast
      cancer and hip fractures. RESULTS: 601 GI bleeds were observed in the 21 462
      subjects in the high-affinity group versus 333 among the 14 927 subjects in the
      lower affinity group (adjusted RR: 1.17, 95% CI 1.02 to 1.34). Similarly, 776
      strokes were observed in the high-affinity group versus 434 in the lower affinity
      treatment group (adjusted RR: 1.18, 95% CI 1.06 to 1.32). No significant
      association with risk for a priori negative control outcomes, including acute
      liver failure, acute renal failure, asthma, breast cancer and hip fractures, was
      identified. CONCLUSIONS: Use of antidepressants with high affinity for the
      serotonin transporter may confer modestly elevated risk for GI and other bleeding
      complications. While multiple methodologic limitations must be considered, these
      results suggest that antidepressants with lower serotonin receptor affinity may
      be preferred in patients at greater risk for such complications.

PMID- 22466035
TI  - Multimodal observational assessment of quality and productivity benefits from the
      implementation of wireless technology for out of hours working.
AB  - OBJECTIVES: The authors investigated if a wireless system of call handling and
      task management for out of hours care could replace a standard pager-based system
      and improve markers of efficiency, patient safety and staff satisfaction. DESIGN:
      Prospective assessment using both quantitative and qualitative methods, including
      interviews with staff, a standard satisfaction questionnaire, independent
      observation, data extraction from work logs and incident reporting systems and
      analysis of hospital committee reports. SETTING: A large teaching hospital in the
      UK. PARTICIPANTS: Hospital at night co-ordinators, clinical support workers and
      junior doctors handling approximately 10 000 tasks requested out of hours per
      month. OUTCOME MEASURES: Length of hospital stay, incidents reported, co
      ordinator call logging activity, user satisfaction questionnaire, staff
      interviews. RESULTS: Users were more satisfied with the new system (satisfaction
      score 62/90 vs 82/90, p=0.0080). With the new system over 70 h/week of co
      ordinator time was released, and there were fewer untoward incidents related to
      handover and medical response (OR=0.30, p=0.02). Broad clinical measures (cardiac
      arrest calls for peri-arrest situations and length of hospital stay) improved
      significantly in the areas covered by the new system. CONCLUSIONS: The
      introduction of call handling software and mobile technology over a medical-grade
      wireless network improved staff satisfaction with the Hospital at Night system.
      Improvements in efficiency and information flow have been accompanied by a
      reduction in untoward incidents, length of stay and peri-arrest calls.

PMID- 22466036
TI  - How does capacity building of health managers work? A realist evaluation study
      protocol.
AB  - INTRODUCTION: There has been a lot of attention on the role of human resource
      management interventions to improve delivery of health services in low- and
      middle-income countries. However, studies on this subject are few due to limited
      research on implementation of programmes and methodological difficulties in
      conducting experimental studies on human resource interventions. The authors
      present the protocol of an evaluation of a district-level capacity-building
      intervention to identify the determinants of performance of health workers in
      managerial positions and to understand how changes (if any) are brought about.
      METHODS AND ANALYSIS: The aim of this study is to understand how capacity
      building works. The authors will use realist evaluation to evaluate an
      intervention in Karnataka, India. The intervention is a capacity-building
      programme that seeks to improve management capacities of health managers at
      district and subdistrict levels through periodic classroom-based teaching and
      mentoring support at the workplace. The authors conducted interviews and reviewed
      literature on capacity building in health to draw out the programme theory of the
      intervention. Based on this, the authors formulated hypothetical pathways
      connecting the expected outcomes of the intervention (planning and supervision)
      to the inputs (contact classes and mentoring). The authors prepared a
      questionnaire to assess elements of the programme theory-organisational culture,
      self-efficacy and supervision. The authors shall conduct a survey among health
      managers as well as collect qualitative data through interviews with participants
      and non-participants selected purposively based on their planning and supervision
      performance. The authors will construct explanations in the form of context
      mechanism-outcome configurations from the results. This will be iterative and the
      authors will use a realist evaluation framework to refine the explanatory
      theories that are based on the findings to explain and validate an improved
      theory on 'what works for whom and under what conditions'. DISCUSSION: The scope
      for applying realist evaluation to study human resource management interventions
      in health are discussed.

PMID- 22466037
TI  - Tracking the impact of research on policy and practice: investigating the
      feasibility of using citations in clinical guidelines for research evaluation.
AB  - OBJECTIVES: To investigate the feasibility of using research papers cited in
      clinical guidelines as a way to track the impact of particular funding streams or
      sources. SETTING: In recent years, medical research funders have made efforts to
      enhance the understanding of the impact of their funded research and to provide
      evidence of the 'value' of investments in particular areas of research. One of
      the most challenging areas of research evaluation is around impact on policy and
      practice. In the UK, the National Institute of Health and Clinical Excellence
      (NICE) provide clinical guidelines, which bring together current high-quality
      evidence on the diagnosis and treatment of clinical problems. Research referenced
      in these guidelines is an indication of its potential to have real impact on
      health policy and practice. DESIGN: This study is based on analysis of the
      authorship and funding attribution of research cited in two NICE clinical
      guidelines: dementia and chronic obstructive pulmonary disease. RESULTS: Analysis
      identified that around a third of papers cited in the two NICE guidelines had at
      least one author based in the UK. In both cases, about half of these UK
      attributed papers contained acknowledgements which allowed the source of funding
      for the research to be identified. The research cited in these guidelines was
      found to have been supported by a diverse set of funders from different sectors.
      The study also investigated the contribution of research groups based in
      universities, industry and the public sector. CONCLUSIONS: The study found that
      there is great potential for guidelines to be used as sources of information on
      the quality of the research used in their development and that it is possible to
      track the source of the funding of the research. The challenge is in harnessing
      the relevant information to track this in an efficient way.

PMID- 22466038
TI  - PROSpER: PReferences for the Organisation of acute health Services for oldER
      people: protocol for a mixed methods study.
AB  - BACKGROUND: Organisation of acute care services for people living in residential
      aged care facilities (RACF) is a complex area of health policy. For people living
      in RACF, the emergency department is often used to provide acute care; needs of
      RACF residents, however, are not always well met. Alternative models of
      delivering care must be acceptable to a variety of stakeholders; however, little
      is known about the values and preferences that people attach to aspects of how
      and where care is delivered. METHODS/DESIGN: The PROSpER Study examines people's
      preferences for the organisation of acute healthcare services for older people in
      RACF. The authors aim to (1) determine which factors influence preferences of
      residents, carers and providers for how and where acute care is delivered and (2)
      determine the relative importance of these factors and the acceptable trade-offs
      between them. Qualitative and quantitative methods will be used. One-on-one
      interviews will be conducted with RACF residents, their families, staff of RACF
      and emergency department staff. A discrete choice study will then be designed to
      quantitatively assess preferences for alternative models of care delivery.
      Approximately 600 respondents from three respondent groups will be surveyed:
      older people living in RACF, family members of aged care residents and staff of
      RACF. A mixed logit model will be used; results will be expressed as parameter
      estimates (beta) and odds of choosing one option over an alternative. Trade-offs
      between attributes will also be calculated. ETHICS AND DISSEMINATION: The PROSpER
      Study has been approved by the University of Sydney, Human Research Ethics
      Committee (Protocol numbers 10653 and 14382) and Royal Perth Hospital Ethics
      Committee (reference 2009/045). Results will be published in peer-reviewed
      scientific journals and via conference presentations; a newsletter will also be
      provided to study participants. A stakeholder roundtable will also be held to
      discuss the results.

PMID- 22466040
TI  - Short-term genetic changes: evaluating effective population size estimates in a
      comprehensively described brown trout (Salmo trutta) population.
AB  - The effective population size (N(e)) is notoriously difficult to accurately
      estimate in wild populations as it is influenced by a number of parameters that
      are difficult to delineate in natural systems. The different methods that are
      used to estimate N(e) are affected variously by different processes at the
      population level, such as the life-history characteristics of the organism, gene
      flow, and population substructure, as well as by the frequency patterns of
      genetic markers used and the sampling design. Here, we compare N(e) estimates
      obtained by different genetic methods and from demographic data and elucidate how
      the estimates are affected by various factors in an exhaustively sampled and
      comprehensively described natural brown trout (Salmo trutta) system. In general,
      the methods yielded rather congruent estimates, and we ascribe that to the
      adequate genotyping and exhaustive sampling. Effects of violating the assumptions
      of the different methods were nevertheless apparent. In accordance with
      theoretical studies, skewed allele frequencies would underestimate temporal
      allele frequency changes and thereby upwardly bias N(e) if not accounted for.
      Overlapping generations and iteroparity would also upwardly bias N(e) when
      applied to temporal samples taken over short time spans. Gene flow from a
      genetically not very dissimilar source population decreases temporal allele
      frequency changes and thereby acts to increase estimates of N(e). Our study
      reiterates the importance of adequate sampling, quantification of life-history
      parameters and gene flow, and incorporating these data into the N(e) estimation.

PMID- 22466039
TI  - APL-1, the Alzheimer's Amyloid precursor protein in Caenorhabditis elegans,
      modulates multiple metabolic pathways throughout development.
AB  - Mutations in the amyloid precursor protein (APP) gene or in genes that process
      APP are correlated with familial Alzheimer's disease (AD). The biological
      function of APP remains unclear. APP is a transmembrane protein that can be
      sequentially cleaved by different secretases to yield multiple fragments, which
      can potentially act as signaling molecules. Caenorhabditis elegans encodes one
      APP-related protein, APL-1, which is essential for viability. Here, we show that
      APL-1 signaling is dependent on the activity of the FOXO transcription factor DAF
      16 and the nuclear hormone receptor DAF-12 and influences metabolic pathways such
      as developmental progression, body size, and egg-laying rate. Furthermore, apl
      1(yn5) mutants, which produce high levels of the extracellular APL-1 fragment,
      show an incompletely penetrant temperature-sensitive embryonic lethality. In a
      genetic screen to isolate mutants in which the apl-1(yn5) lethality rate is
      modified, we identified a suppressor mutation in MOA-1/R155.2, a receptor-protein
      tyrosine phosphatase, and an enhancer mutation in MOA-2/B0495.6, a protein
      involved in receptor-mediated endocytosis. Knockdown of apl-1 in an apl-1(yn5)
      background caused lethality and molting defects at all larval stages, suggesting
      that apl-1 is required for each transitional molt. We suggest that signaling of
      the released APL-1 fragment modulates multiple metabolic states and that APL-1 is
      required throughout development.

PMID- 22466041
TI  - Functional genomic architecture of predisposition to voluntary exercise in mice:
      expression QTL in the brain.
AB  - The biological basis of voluntary exercise is complex and simultaneously
      controlled by peripheral (ability) and central (motivation) mechanisms. The
      accompanying natural reward, potential addiction, and the motivation associated
      with exercise are hypothesized to be regulated by multiple brain regions,
      neurotransmitters, peptides, and hormones. We generated a large (n = 815)
      advanced intercross line of mice (G(4)) derived from a line selectively bred for
      increased wheel running (high runner) and the C57BL/6J inbred strain. We
      previously mapped multiple quantitative trait loci (QTL) that contribute to the
      biological control of voluntary exercise levels, body weight, and composition, as
      well as changes in body weight and composition in response to short-term
      exercise. Currently, using a subset of the G(4) population (n = 244), we examined
      the transcriptional landscape relevant to neurobiological aspects of voluntary
      exercise by means of global mRNA expression profiles from brain tissue. We
      identified genome-wide expression quantitative trait loci (eQTL) regulating
      variation in mRNA abundance and determined the mode of gene action and the cis-
      and/or trans-acting nature of each eQTL. Subsets of cis-acting eQTL, colocalizing
      with QTL for exercise or body composition traits, were used to identify candidate
      genes based on both positional and functional evidence, which were further
      filtered by correlational and exclusion mapping analyses. Specifically, we
      discuss six plausible candidate genes (Insig2, Socs2, DBY, Arrdc4, Prcp, IL15)
      and their potential role in the regulation of voluntary activity, body
      composition, and their interactions. These results develop a potential initial
      model of the underlying functional genomic architecture of predisposition to
      voluntary exercise and its effects on body weight and composition within a
      neurophysiological framework.

PMID- 22466043
TI  - Investigating natural variation in Drosophila courtship song by the evolve and
      resequence approach.
AB  - A primary goal of population genetics is to determine the genetic basis of
      natural trait variation. We could significantly advance this goal by developing
      comprehensive genome-wide approaches to link genotype and phenotype in model
      organisms. Here we combine artificial selection with population-based
      resequencing to investigate the genetic basis of variation in the interpulse
      interval (IPI) of Drosophila melanogaster courtship song. We performed divergent
      selection on replicate populations for only 14 generations, but had considerable
      power to differentiate alleles that evolved due to selection from those that
      evolved stochastically. We identified a large number of variants that changed
      frequency in response to selection for this simple behavior, and they are highly
      underrepresented on the X chromosome. Though our power was adequate using this
      experimental technique, the ability to differentiate causal variants from those
      affected by linked selection requires further development.

PMID- 22466044
TI  - There are endless calls for health system reform in countries across the globe.
      Introduction.

PMID- 22466042
TI  - Analysis of Cryptococcus neoformans sexual development reveals rewiring of the
      pheromone-response network by a change in transcription factor identity.
AB  - The fundamental mechanisms that control eukaryotic development include extensive
      regulation at the level of transcription. Gene regulatory networks, composed of
      transcription factors, their binding sites in DNA, and their target genes, are
      responsible for executing transcriptional programs. While divergence of these
      control networks drives species-specific gene expression that contributes to
      biological diversity, little is known about the mechanisms by which these
      networks evolve. To investigate how network evolution has occurred in fungi, we
      used a combination of microarray expression profiling, cis-element
      identification, and transcription-factor characterization during sexual
      development of the human fungal pathogen Cryptococcus neoformans. We first
      defined the major gene expression changes that occur over time throughout sexual
      development. Through subsequent bioinformatic and molecular genetic analyses, we
      identified and functionally characterized the C. neoformans pheromone-response
      element (PRE). We then discovered that transcriptional activation via the PRE
      requires direct binding of the high-mobility transcription factor Mat2, which we
      conclude functions as the elusive C. neoformans pheromone-response factor. This
      function of Mat2 distinguishes the mechanism of regulation through the PRE of C.
      neoformans from all other fungal systems studied to date and reveals species
      specific adaptations of a fungal transcription factor that defies predictions on
      the basis of sequence alone. Overall, our findings reveal that pheromone-response
      network rewiring has occurred at the level of transcription factor identity,
      despite the strong conservation of upstream and downstream components, and serve
      as a model for how selection pressures act differently on signaling vs. gene
      regulatory components during eukaryotic evolution.

PMID- 22466045
TI  - The fox and the grapes: is real reform beyond reach in the United States?
AB  - As the challenges of maintaining (or, in the US case, attaining) affordable
      universal coverage multiply, the debate about what constitutes "real" reform
      intensifies in Western health care systems. The reality of reform, however, lies
      in the eyes of myriad beholders who variously enshrine consumer responsibility,
      changes in payment systems, reorganization, and other strategies -- or some
      encompassing combination of all of the above -- as the essential ingredient(s).
      This debate, increasingly informed by the agendas of health services researchers
      and health policy analysts, arguably serves as much or more to becloud as to
      clarify the practical options policy makers face and remains severely imbalanced
      with respect to the institutional sectors on which it concentrates, the fields of
      knowledge on which it draws, and the roles it envisions for markets and the
      state.

PMID- 22466046
TI  - A conversation with Donald Berwick on implementing national health reform.
AB  - Michael Birnbaum interviews Donald Berwick shortly after his departure from the
      Centers for Medicare and Medicaid Services about the national health care
      landscape. Berwick discusses the strategic vision, policy levers, operational
      challenges, and political significance of federal health care reform. He rejects
      the notion that the Affordable Care Act represents a government takeover of
      health care financing or service delivery but says the law's Medicaid expansion
      and its creation of health benefit exchanges present a "watershed moment for
      American federalism." Berwick argues that the solution to Medicare's cost
      containment challenge lies in quality improvement. He is optimistic that
      accountable care organizations can deliver savings and suggests that shifting
      risk downstream to providers throws the health insurance model into question.
      Finally, looking to the future, Berwick sees a race against time to make American
      health care more affordable.

PMID- 22466047
TI  - Markets and targets in the English National Health Service: is there a role for
      behavioral economics?
AB  - Over the past twenty years, the emphasis of reform attempts to improve efficiency
      within the English National Health Service (NHS) has oscillated between markets
      and targets. Both strategies are informed by standard economic theory but thus
      far have achieved varying degrees of success. Behavioral economics is currently
      in vogue and offers an alternative (or, in some cases, a complement) to standard
      economic theory on what motivates human behavior. There are many aspects to
      behavioral economics, but space constraints allow just three to be considered
      here: identity, loss aversion, and hyperbolic discounting. An attempt is made in
      this article to speculate on the extent to which these three concepts can explain
      the success or otherwise of the NHS market and target policies of the last two
      decades, and some suggestions are offered as to how policies might be usefully
      designed in the future. Arguably the key points are that people are more likely
      to be motivated if they identify with the ethos of the policy; the threat of
      losses will often provoke more of a response than the promise of gains; and the
      "immediate moment" matters enormously to individuals, so policies that require
      human action should be designed to make that moment as enjoyable (or as pain
      free) as possible.

PMID- 22466048
TI  - Maryland exceptionalism? All-payers regulation and health care system efficiency.

PMID- 22466049
TI  - A democratic responsiveness approach to real reform: an exploration of health
      care systems' resilience.
AB  - Real reforms attempt to change how health care is financed and how it is
      rationed. Three main explanations have been offered to explain why such reforms
      are so difficult: institutional gridlock, path dependency, and societal
      preferences. The latter posits that choices made regarding the health care system
      in a given country reflect the broader societal set of values in that country and
      that as a result public resistance to real reform may more accurately reflect
      citizens' personal convictions, self-interest, or even active social choices.
      "Conscientious objectors" may do more to derail reform than previously
      recognized.

PMID- 22466050
TI  - Real reform in health systems: an introduction.

PMID- 22466051
TI  - Reform and the politics of hybridization in mature health care states.
AB  - This article examines the cases of three health care states -- two of which
      (Britain and the Netherlands) have undergone major policy reform and one of which
      (Canada) has experienced only marginal adjustments. The British and Dutch reforms
      have variously altered the balance of power, the mix of instruments of control,
      and the organizing principles. As a result, mature systems representing the ideal
      typical health care state categories of national health systems and social
      insurance (Britain and the Netherlands, respectively) were transformed into
      distinctive national hybrids. These processes have involved a politics of
      redesign that differs from the politics of earlier phases of establishment and
      retrenchment. In particular, the redesign phase is marked by the activity of
      institutional entrepreneurs who exploit specific opportunities afforded by public
      programs to combine public and private resources in innovative organizational
      arrangements. Canada stands as a counterpoint: no window of opportunity for major
      change occurred, and the bilateral monopoly created by its prototypical single
      payer model provided few footholds for entrepreneurial activity. The increased
      significance of institutional entrepreneurs gives greater urgency to one of the
      central projects of health policy: the design of accountability frameworks to
      allow for an assessment of performance against objectives.

PMID- 22466052
TI  - All-payer state systems.

PMID- 22466053
TI  - Real reform begins within: an organizational approach to health care reform.
AB  - Health care systems are under pressure to control their increasing costs, to
      better adapt to evolving demands, to improve the quality and safety of care, and
      ultimately to ameliorate the health of their populations. This article looks at a
      battery of organizational options aimed at transforming health care systems and
      argues that more attention must be paid to reforming the delivery mechanisms that
      are so crucial for health care systems' overall performance. To support
      improvement, policies can rely on organizational assets in two ways. First,
      reforms can promote the creation of new organizational forms; second, they can
      employ organizational levers (e.g., capacity development, team-based
      organizations, evidence-informed practices) to achieve specific policy goals. In
      both cases organizational assets are mobilized with a view to creating complete
      health care organizations -- that is to say, organizations that have the capacity
      to function as high-performing systems. The challenges confronting the
      development of more complete health care organizations are significant. Real
      health care system reforms may likewise require implementing ecologies of complex
      innovation at the clinical, organizational, and policy levels. Policies play a
      determining role in shaping these new spaces for action so that day-to-day
      practices may change.

PMID- 22466054
TI  - The case for a coordinated system of provider payments in the United States.

PMID- 22466055
TI  - Systematic determinations of SUMOylation activation intermediates and dynamics by
      a sensitive and quantitative FRET assay.
AB  - Ubiquitination and SUMOylation are multi-step cascade reactions, in which small
      protein modifiers are activated by E1 activating enzyme, transferred to E2
      conjugating enzyme, and conjugated to substrates mediated by the E3 ligase in
      vivo. The structural and biochemical bases for the cascade reactions have been
      elucidated by several studies. However, the reaction intermediates and dynamics
      of these peptide modifiers among the enzymes have not been completely elucidated.
      Here we report detailed investigations of SUMOylation dynamics and interaction
      switches of SUMO1 among its ligases using FRET technology. These studies show
      that, while SUMO1 and the E1 subunit Aos1 or Uba2 have no intrinsic affinity for
      each other, the adenylation of SUMO1 carried out by Aos1 requires the presence of
      Uba2, and subsequently conformational changes trigger the interaction of SUMO1
      and Uba2 for a thioester bond formation. The reaction intermediates among SUMO1
      and its ligases are indirectly revealed by FRET signals generated by each pair.
      Furthermore, the transfer of SUMO1 from Uba2 to E2 enzyme, Ubc9, depends on the
      formation of a thioester bond between SUMO1 and Ubc9, and requires non-covalent
      interaction between Ubc9 and Uba2, but not between Ubc9 and SUMO1. These
      interaction switches provide the physical and biochemical bases for the SUMO
      activation and a transfer cascade required for SUMO activation.

PMID- 22466057
TI  - Surfactant protein A (SP-A) and angiotensin converting enzyme (ACE) as early
      biomarkers for pulmonary edema formation in ventilated human lung lobes.
AB  - OBJECTIVE: Ex vivo perfused and ventilated lung lobes frequently develop
      pulmonary edema. We were looking for a suitable and early detectable biomarker in
      the perfusion fluid indicating lung cell damage and loss of tissue integrity in
      ventilated human lung lobes. Therefore, we elucidated whether surfactant protein
      A (SP-A) and angiotensin-converting enzyme (ACE) were measurable in the perfusion
      fluid and whether they were suitable indicators for edema formation occurring
      within the experimental time frame of 1-2 h. METHODS: Patients (n = 39)
      undergoing a lobectomy, bilobectomy or pneumonectomy due to primary bronchial
      cell carcinoma were included in the studies. Lung lobes were extracorporally
      ventilated and perfused for up to 2 h. Two different perfusion fluids were used,
      plain perfusion buffer and perfusion buffer containing packed erythrocytes or
      buffy coats. Perfusion fluid samples were analyzed for SP-A and ACE using
      immunoassays served as perfusion fluids. RESULTS: SP-A and ACE concentrations
      were analyzed in fluid sample sets of 39 and 33 perfusion experiments,
      respectively. Degrees of edema formation were arbitrarily classified into three
      groups (<= 29, 30-59, >= 60 % weight gain). The maximum increase of SP-A and ACE
      concentrations in the perfusate was significantly higher for more pronounced
      edemas in case of perfusions using a mixture of blood components and buffer.
      Interestingly, the time courses of ACE and SP-A were highly similar. CONCLUSION:
      We suggest that SP-A and ACE are promising early biochemical markers for the
      development for pulmonary edema formation in the ex vivo lung lobe perfusion.

PMID- 22466059
TI  - Antipsychotic monotherapy and adjuvant psychotropic therapies in schizophrenia
      patients:  effect on time to readmission.
AB  - This study assessed the relationship between pharmacological regimens at hospital
      discharge and hospital readmission among schizophrenia patients. The records
      reviewed were all consecutive admissions (N=720) from a specific catchment area
      during the period 1991-2005. Two main groups were selected for analysis: the
      first group (N=537) included patients discharged with first-generation
      antipsychotics (FGA), and the second group (N=183) included patients with second
      generation antipsychotics (SGA). Data on clinical and demographic characteristics
      at discharge, including a brief psychiatric rating scale and pharmacological
      treatment, were collected. The rate of readmission within 12 months was analyzed
      in relation to the specific pharmacological treatment at discharge. There was no
      significant difference in the risk of readmission in patients treated with SGA
      compared with FGA. Adjuvant psychotropic medications to either FGA or SGA did not
      attenuate the risk of readmission. The readmission rate in patients treated with
      clozapine (N=74) was significantly lower in comparison with depot FGA (N=293)
      medications (P=0.016). There was no advantage of SGA over FGA, with or without
      adjuvant psychotropic treatment, with regard to rehospitalization risk during the
      12-month follow-up. Clozapine was found to reduce the risk for readmission in
      comparison with depot FGA.

PMID- 22466058
TI  - Efficacy of adjunctive aripiprazole in patients with major depressive disorder
      who showed minimal response to initial antidepressant therapy.
AB  - To evaluate the efficacy of adjunctive aripiprazole in patients with minimal
      response to prior antidepressant therapy (ADT). Pooled data from three
      randomized, double-blind, placebo-controlled studies assessing the efficacy of
      adjunctive aripiprazole to ADT in patients with major depressive disorder who had
      a minimal response [< 25% reduction on the Montgomery-Asberg Depression Rating
      Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind
      adjunctive phase, response was defined as at least 50% reduction in the MADRS
      score and remission as at least 50% reduction in MADRS score and a MADRS score <=
      10. Rates were examined using analysis of covariance and Cochran-Mantel-Haenszel
      tests. Kaplan-Meier curves were used to calculate time to response and remission.
      Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal
      responder). Time to response and remission were significantly shorter for ADT
      minimal responders receiving aripiprazole+ADT versus adjunctive placebo+ADT. ADT
      minimal responders on aripiprazole+ADT showed significantly greater improvements
      in MADRS score at endpoint compared with minimal responders on placebo+ADT (-10.3
      vs. -6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly
      higher response rates with aripiprazole+ADT than placebo+ADT (36 vs. 19%,
      respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively,
      P<0.0001). The numbers needed to treat with aripiprazole+ADT were six for
      response and eight for remission. Aripiprazole augmentation had a rapid and
      clinically meaningful effect in ADT minimal responders.

PMID- 22466060
TI  - Radiofrequency-assisted liposuction device for body contouring: 97 patients under
      local anesthesia.
AB  - BACKGROUND: Radiofrequency-assisted liposuction involves the delivery of a
      controlled amount of energy to treated tissue resulting in fat liquefaction,
      accompanying hemostasis, and skin tightening. The purpose of this study is to
      report experience with a larger sample size using the BodyTiteTM radiofrequency
      assisted liposuction (RFAL) platform, and its first use with local tumescent
      anesthesia. The BodytiteTM device is currently awaiting FDA approval. METHODS: We
      prospectively included 97 patients who underwent radiofrequency-assisted
      liposuction under local anesthesia under IRB approval. We treated 144 anatomical
      areas in 132 operations and collected the following data: age, sex, height,
      weight, body mass index (BMI), anatomical area of treatment, operative time,
      amount of tumescent solution used, amount of fat aspirated, amount of kilojoules
      (kJ) delivered, and the incidence of infections, seromas, adverse effects from
      medications, and thermal injuries. Patients were asked to complete an online
      survey assessing the aesthetic outcome and quality of life after treatment with
      RFAL-assisted liposuction. Three independent plastic surgeons were asked to
      evaluate photographs of our 6-month postoperative results in comparison to the
      preoperative photos. RESULTS: The average age and BMI of our study population was
      37.6 years and 28.2 kg/m2, respectively. The study population was 88% female. The
      mean amount of lidocaine given per treatment session was 32.7 mg/kg (range=3.8
      83.3 mg/kg). The mean amount of tumescent fluid given per anatomical treatment
      area was 1,575 cc. The average amount of total aspirate across all anatomical
      treatment areas was 1,050 cc, with an average total aspirate of 1,146 cc per
      treatment date. The overall incidence of major complications was 6.25% and the
      incidence of minor complications was 8.3%. Overall patient satisfaction was 82%
      for the degree of skin tightening and 85% for the body-contouring result with the
      BodyTiteTM device. Three independent plastic surgeons graded the improvement in
      body contour as good to excellent in 74.5% of patients and the improvement in
      skin tightening as good to excellent in 58.5% of patients. CONCLUSIONS: The
      BodyTiteTM RFAL platform is a safe and effective device for use as an energy
      based liposuction technique under local tumescent anesthesia in the awake
      patient. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors at www.springer.com/00266.

PMID- 22466062
TI  - Abnormalities of the fornix in mild cognitive impairment are related to episodic
      memory loss.
AB  - The fornix is a major efferent tract of the hippocampus, a structure critical for
      normal memory function. However, the role of structural degradation of the fornix
      in memory dysfunction in mild cognitive impairment (MCI) has remained unclear. We
      used diffusion tensor tractography to measure microstructural properties of the
      fornix and the corticospinal tract (CST), as a control tract, in 206 cognitively
      normal subjects, 76 amnestic MCI (aMCI) and 51 non-amnestic MCI (naMCI) subjects.
      Hippocampal volumes were measured using deformation-based morphometry. We found
      significant fractional anisotropy reductions in the left fornix and radial
      diffusivity (RD) increases in bilateral fornices in aMCI, but not in naMCI,
      compared with controls. No significant changes in the CST were found in aMCI
      subjects, but naMCI subjects showed significantly increased RD and axial
      diffusivity of the right CST, compared with controls. Increased left fornical RD
      measure was correlated with poor verbal memory performance in aMCI subjects. In
      addition, reduced microstructural integrity of the fornix was associated with
      hippocampal atrophy in aMCI. This study suggests that microstructural alteration
      of the fornix is a contributor to early episodic memory dysfunction in non
      demented individuals.

PMID- 22466063
TI  - Loss of sensitivity to dynamic occlusion in patients with Alzheimer's disease.
AB  - The current study examined whether diminished sensitivity to dynamic occlusion in
      Alzheimer's disease (AD) contributes to reduced capacity to recover 3D shape from
      motion. Young controls, age-matched elderly controls, and AD patients
      participated in the study. Participants watched computer simulations of an
      object, depicted as either transparent or opaque, rotating about the vertical
      axis against a background rendered in random dot texture. Six geometric solids
      were graphically simulated, each rendered in three texture densities, against
      three different levels of background texture densities. Participants identified
      the displayed object by pointing to the matching wooden object. Young controls
      were most accurate (79%), followed by elderly controls (61%) and AD patients
      (43%). Both control groups identified opaque objects better than transparent
      objects, but AD patients identified both objects equally poorly. These results
      demonstrate that dynamic occlusion (i.e., accretion and deletion of optical
      texture at the occluding edge) facilitates recovery of 3D shape from motion but
      such capacity is severely impaired in AD. The current results suggest the need
      for more research into dynamic occlusion, not only as source of information to
      recover 3D shape from motion, but also as a visual deficit in AD.

PMID- 22466061
TI  - Posterior cingulum white matter disruption and its associations with verbal
      memory and stroke risk in mild cognitive impairment.
AB  - Medial temporal lobe and temporoparietal brain regions are among the earliest
      neocortical sites to undergo pathophysiologic alterations in Alzheimer's disease
      (AD), although the underlying white matter changes in these regions is less well
      known. We employed diffusion tensor imaging to evaluate early alterations in
      regional white matter integrity in participants diagnosed with mild cognitive
      impairment (MCI). The following regions of interests (ROIs) were examined: 1)
      anterior cingulum (AC); 2) posterior cingulum (PC); 3) genu of the corpus
      callosum; 4) splenium of the corpus callosum; and 5) as a control site for
      comparison, posterior limb of the internal capsule. Forty nondemented
      participants were divided into demographically-similar groups based on cognitive
      status (MCI: n = 20; normal control: n = 20), and fractional anisotropy (FA)
      estimates of each ROI were obtained. MCI participants showed greater posterior
      white matter (i.e., PC, splenium) but not anterior white matter (i.e., AC, genu)
      changes, after adjusting for age, stroke risk, and whole brain volume. FA
      differences of the posterior white matter were best accounted for by changes in
      radial but not axial diffusivity. PC FA was also significantly positively
      correlated with hippocampal volume as well as with performance on tests of verbal
      memory, whereas stroke risk was significantly correlated with genu FA and was
      unrelated to PC FA. When investigating subtypes of our MCI population, amnestic
      MCI participants showed lower PC white matter integrity relative to those with
      non-amnestic MCI. Findings implicate involvement of posterior microstructural
      white matter degeneration in the development of MCI-related cognitive changes and
      suggest that reduced FA of the PC may be a candidate neuroimaging marker of AD
      risk.

PMID- 22466064
TI  - Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is generally associated with lower omega-3 fatty acid
      intake from fish but despite numerous studies, it is still unclear whether there
      are differences in omega-3 fatty acids in plasma or brain. In matched plasma and
      brain samples provided by the Memory and Aging Project, fatty acid profiles were
      quantified in several plasma lipid classes and in three brain cortical regions.
      Fatty acid data were expressed as % composition and as concentrations (mg/dL for
      plasma or mg/g for brain). Differences in plasma fatty acid profiles between AD,
      mild cognitive impairment (MCI), and those with no cognitive impairment (NCI)
      were most apparent in the plasma free fatty acids (lower oleic acid isomers and
      omega-6 fatty acids in AD) and phospholipids (lower omega-3 fatty acids in AD).
      In brain, % DHA was lower only in phosphatidylserine of mid-frontal cortex and
      superior temporal cortex in AD compared to NCI (-14% and -12%, respectively; both
      p < 0.05). The only significant correlation between plasma and brain fatty acids
      was between % DHA in plasma total lipids and % DHA in phosphatidylethanolamine of
      the angular gyrus, but only in the NCI group (+0.77, p < 0.05). We conclude that
      AD is associated with altered plasma status of both DHA and other fatty acids
      unrelated to DHA, and that the lipid class-dependent nature of these differences
      reflects a combination of differences in intake and metabolism.

PMID- 22466066
TI  - Quantitative analysis shows that contrast medium in positron emission
      tomography/computed tomography may cause significant artefacts.
AB  - OBJECTIVES: Attenuation correction algorithms are required for accurate
      quantification of PET data and for mapping of radioactive tracers. Modern PET
      systems incorporate computed tomography (CT) systems to perform attenuation
      correction. However, high-density media, such as contrast agents, may introduce
      potentially clinically significant artefacts in PET images when CT-based
      attenuation correction algorithms are used. Although various groups have
      investigated this issue, no study has quantitatively assessed the clinical
      significance of these artefacts by comparing artefact and lesion standardized
      uptake values (SUVs) in controlled phantom experiments. Furthermore, previous
      studies have focussed on the effects of increasing the concentration of contrast
      medium, without investigating the effects of increasing its transaxial area. This
      study quantifies the clinical significance of increasing the concentration and
      transaxial area of contrast agents and evaluates a commercially available
      contrast agent correction algorithm. METHODS: Images of a phantom containing
      background activity, a volume of contrast agent and varying sizes of hot lesions
      were acquired using clinical acquisition protocols. Quantitative analysis was
      performed on transaxial image slices of PET data. RESULTS: The densest medium
      caused a 125% SUV(mean) increase in the area containing, and immediately adjacent
      to, contrast medium when compared with a reference water phantom. As the
      transaxial area of the contrast medium increased, artefacts appeared as a ring of
      activity around the periphery of the contrast medium. The contrast correction
      algorithm reduced these artefacts to within +/- 39% of the reference results.
      CONCLUSION: Oral and IV contrast agents can cause clinically significant
      artefacts in CT-based attenuation-corrected PET images and should be used with
      caution.

PMID- 22466067
TI  - Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: a risk to
      human health?
AB  - Personal care products (PCP) often contain micron- or nano-sized formulation
      components, such as nanoemulsions or microscopic vesicles. A large number of
      studies suggest that such vesicles do not penetrate human skin beyond the
      superficial layers of the stratum corneum. Nano-sized PCP formulations may
      enhance or reduce skin absorption of ingredients, albeit at a limited scale.
      Modern sunscreens contain insoluble titanium dioxide (TiO2) or zinc oxide (ZnO)
      nanoparticles (NP), which are efficient filters of UV light. A large number of
      studies suggest that insoluble NP do not penetrate into or through human skin. A
      number of in vivo toxicity tests, including in vivo intravenous studies, showed
      that TiO2 and ZnO NP are non-toxic and have an excellent skin tolerance.
      Cytotoxicity, genotoxicity, photo-genotoxicity, general toxicity and
      carcinogenicity studies on TiO2 and ZnO NP found no difference in the safety
      profile of micro- or nano-sized materials, all of which were found to be non
      toxic. Although some published in vitro studies on insoluble nano- or micron
      sized particles suggested cell uptake, oxidative cell damage or genotoxicity,
      these data are consistent with those from micron-sized particles and should be
      interpreted with caution. Data on insoluble NP, such as surgical implant-derived
      wear debris particles or intravenously administered magnetic resonance contrast
      agents suggest that toxicity of small particles is generally related to their
      chemistry rather than their particle size. Overall, the weight of scientific
      evidence suggests that insoluble NP used in sunscreens pose no or negligible risk
      to human health, but offer large health benefits, such as the protection of human
      skin against UV-induced skin ageing and cancer.

PMID- 22466068
TI  - Nanostructured calcium silicate hydrate seeds accelerate concrete hardening: a
      combined assessment of benefits and risks.
AB  - Nanotechnology creates new possibilities to control and improve material
      properties for civil infrastructure. Special focus in this area is put on
      Portland cement and gypsum. Together their annual production is by far larger
      than for any other material worldwide. Nanomodification of these materials can be
      done during the few hours between dissolution and hardening, especially by
      nucleation of the re-crystallization with suitable colloids. Here we report first
      results in homogeneous seeding of the precipitation of calcium silicate hydrates
      within a real Portland cement composition. The occupational safety during the
      production phase and during mixing of concrete paste is addressed in detail by in
      vivo testing. We perform 5-day inhalation with 21-day recovery in rats and
      analyze organ-specific toxicity and 71 endpoints from bronchoalveolar lavage
      (BALF) and blood. In BALF parameters, no test-related changes were observed,
      indicating the generally low toxicity of the test material. Some mild lesions
      were observed in larynx level. In the lungs, all animals of the 50 mg/m3
      concentration group revealed a minimal to mild increase in alveolar macrophages,
      which recovered back to control level.

PMID- 22466069
TI  - Paradoxical cytotoxicity of tert-butylhydroquinone in vitro: What kills the
      untreated cells?
AB  - At high concentrations, tert-butylhydroquinone (tBHQ), a phenolic antioxidant
      frequently used as a food preservative, exerts cytotoxic effects, which are
      closely linked to its ability to form reactive oxygen species as a consequence of
      redox cycling processes. Here we describe that treatment of murine 3T3 cells with
      300 MUg/ml of tBHQ in 96-well culture plates induces the death of untreated cells
      in neighboring wells on the same plate. The mechanisms underlying that effect
      were investigated. Death of the seemingly untreated neighboring cells was caused
      by the more toxic and volatile tBHQ oxidation product tert-butyl-p-benzoquinone
      (tBQ) present at up to 3 MUg/ml in the untreated neighboring wells. tBQ was
      formed from tBHQ in a non-enzymatic process involving copper ions and oxygen. The
      unexpected perturbation of cytotoxicity testing following treatment with tBHQ by
      its volatile metabolite tBQ shows that not only metabolic processes but also non
      enzymatic mechanisms have to be considered as important parameters for in vitro
      assays. Furthermore, our data show that even cells several wells away from the
      treated wells do not necessarily constitute proper "untreated" controls when
      cells are treated with the frequently used compound tBHQ. This might lead to an
      underestimation of the effects observed on the Nrf2 signaling pathway, where tBHQ
      is frequently used as an inductor in vitro.

PMID- 22466070
TI  - Sexual dimorphism of cadmium-induced toxicity in rats: involvement of sex
      hormones.
AB  - The toxic effect of cadmium varies with sex in experimental animals. Previous
      studies have demonstrated that pretreatment of male Fischer 344 (F344) rats with
      the female sex hormone progesterone markedly enhances the susceptibility to
      cadmium, suggesting a role for progesterone in the sexual dimorphism of cadmium
      toxicity. In the present study, we attempted to further elucidate the mechanism
      for sex differences in cadmium-induced toxicity in F344 rats. A single exposure
      to cadmium (5.0 mg Cd/kg, sc) was lethal in 10/10 (100 %) female compared with
      6/10 (60 %) male rats. Using a lower dose of cadmium (3.0 mg Cd/kg), circulating
      alanine aminotransferase activity, indicative of hepatotoxicity, was highly
      elevated in the cadmium treated females but not in males. However, no gender
      based differences occurred in the hepatic cadmium accumulation, metallothionein
      or glutathione levels. When cadmium (5.0 mg Cd/kg) was administered to young rats
      at 5 weeks of age, the sex-related difference in lethality was minimal.
      Furthermore, although ovariectomy blocked cadmium-induced lethality, the lethal
      effects of the metal were restored by pretreatment with progesterone (40 mg/kg,
      sc, 7 consecutive days) or beta-estradiol (200 MUg/kg, sc, 7 consecutive days) to
      ovariectomized rats. These results provide further evidence that female sex
      hormones such as progesterone and beta-estradiol are involved in the sexual
      dimorphism of cadmium toxicity in rats.

PMID- 22466071
TI  - Similar distribution changes of GABAergic interneuron subpopulations in contrast
      to the different impact on neurogenesis between developmental and adult-stage
      hypothyroidism in the hippocampal dentate gyrus in rats.
AB  - Hypothyroidism affects neurogenesis. The present study was performed to clarify
      the sensitivity of neurogenesis-related cellular responses in the hippocampal
      dentate gyrus between developmental and adult-stage hypothyroidism. An exposure
      study of methimazole (MMI) as an anti-thyroid agent at 0, 50, 200 ppm in the
      drinking water was performed using pregnant rats from gestation day 10 to
      postnatal day (PND) 21 (developmental hypothyroidism) and adult male rats by
      setting an identical exposure period from PND 46 through to PND 77 (adult-stage
      hypothyroidism). Offspring with developmental hypothyroidism were killed at PND
      21 or PND 77, and animals with adult-stage hypothyroidism were killed at PND 77.
      Proliferation and apoptosis were unchanged in the dentate subgranular zone by
      either developmental or adult-stage hypothyroidism. With regard to precursor
      granule cells, a sustained reduction of paired box 6-positive stem or early
      progenitor cells and a transient reduction of doublecortin-positive late-stage
      progenitor cells were observed after developmental hypothyroidism with MMI at 50
      and 200 ppm. These cells were unchanged by adult-stage hypothyroidism. With
      regard to gamma-aminobutyric acid (GABA) ergic interneuron subpopulations in the
      dentate hilus, the number of parvalbumin-positive cells was decreased and the
      number of calretinin-positive cells was increased after both developmental and
      adult-stage hypothyroidism with MMI at 50 and 200 ppm. Fluctuations in GABAergic
      interneuron numbers with developmental hypothyroidism continued through to PND 77
      with 200 ppm MMI. Considering the roles of GABAergic interneuron subpopulations
      in neurogenesis and neuronal differentiation, subpopulation changes in GABAergic
      interneurons by hypothyroidism may be the signature of aberrant neurogenesis even
      at the adult stage.

PMID- 22466072
TI  - The importance of HbA1c and glucose variability in patients with type 1 and type
      2 diabetes: outcome of continuous glucose monitoring (CGM).
AB  - Glucose variability has recently been investigated in diabetic patients in
      several studies, but most of them considered only a few variability indicators
      and did not systematically correlate them with patients' HbA1c levels and other
      important characteristics. In thus study, the correlations between HbA1c levels
      and metabolic control (average glucose, AG), glucose variability (SD, CONGA,
      MAGE, MODD, BG ROC), hyperglycemia (HBGI), hypoglycemia (LBGI) and postprandial
      (AUC PP) indices were investigated in patients with type 1 and type 2 diabetes.
      The study involved 68 patients divided into 3 groups as follows: 35 patients had
      type 1 diabetes (group 1); 17 had type 2 diabetes and were taking multiple daily
      injections (MDI) of insulin (group 2); and 16 patients had type 2 diabetes
      treated with OHA and/or basal insulin (group 3). The indicators were obtained
      over at least 48 h using a continuous glucose monitoring (CGM) system. HbA1c
      levels were measured at the baseline and after CGM. HbA1c correlated
      significantly with AG (r = 0.74), AUC PP (r = 0.69) and HBGI (r = 0.74), but only
      in type 1 diabetic patients. Patients with longstanding disease and type 1
      diabetes had a greater glucose variability, irrespective of their HbA1c levels.
      Insulin therapy with MDI correlated strongly with HbA1c, but not with glucose
      variability. HbA1c levels identify states of sustained hyperglycemia and seem to
      be unaffected by hypoglycemic episodes or short-lived glucose spikes,
      consequently revealing shortcomings as a "gold standard" indicator of metabolic
      control. Glucose variability indicators describe the glucose profile of type 1
      diabetic patients and identify any worsening glycemic control (typical of
      longstanding diabetes) more accurately than HbA1c tests.

PMID- 22466073
TI  - Effect of electrostatics on aggregation of prion protein Sup35 peptide.
AB  - Self-assembly of misfolded proteins into ordered fibrillar structures is a
      fundamental property of a wide range of proteins and peptides. This property is
      also linked with the development of various neurodegenerative diseases such as
      Alzheimer's and Parkinson's. Environmental conditions modulate the misfolding and
      aggregation processes. We used a peptide, CGNNQQNY, from yeast prion protein
      Sup35, as a model system to address effects of environmental conditions on
      aggregate formation. The GNNQQNY peptide self-assembles in fibrils with
      structural features that are similar to amyloidogenic proteins. Atomic force
      microscopy (AFM) and thioflavin T (ThT) fluorescence assay were employed to
      follow the aggregation process at various pHs and ionic strengths. We also used
      single molecule AFM force spectroscopy to probe interactions between the peptides
      under various conditions. The ThT fluorescence data showed that the peptide
      aggregates fast at pH values approaching the peptide isoelectric point (pI = 5.3)
      and the kinetics is 10 times slower at acidic pH (pH 2.0), suggesting that
      electrostatic interactions contribute to the peptide self-assembly into
      aggregates. This hypothesis was tested by experiments performed at low (11 mM)
      and high (150 mM) ionic strengths. Indeed, the aggregation lag time measured at
      pH 2 at low ionic strength (11 mM) is 195 h, whereas the lag time decreases ~5
      times when the ionic strength is increased to 150 mM. At conditions close to the
      pI value, pH 5.6, the aggregation lag time is 12 +/- 6 h under low ionic
      strength, and there is minimal change to the lag time at 150 mM NaCl. The ionic
      strength also influences the morphology of aggregates visualized with AFM. In pH
      2.0 and at high ionic strength, the aggregates are twofold taller than those
      formed at low ionic strength. In parallel, AFM force spectroscopy studies
      revealed minimal contribution of electrostatics to dissociation of transient
      peptide dimers.

PMID- 22466074
TI  - Reverse transmission along the ossicular chain in gerbil.
AB  - In a healthy cochlea stimulated with two tones f (1) and f (2), combination tones
      are generated by the cochlea's active process and its associated nonlinearity.
      These distortion tones travel "in reverse" through the middle ear. They can be
      detected with a sensitive microphone in the ear canal (EC) and are known as
      distortion product otoacoustic emissions. Comparisons of ossicular velocity and
      EC pressure responses at distortion product frequencies allowed us to evaluate
      the middle ear transmission in the reverse direction along the ossicular chain.
      In the current study, the gerbil ear was stimulated with two equal-intensity
      tones with fixed f (2)/f (1) ratio of 1.05 or 1.25. The middle ear ossicles were
      accessed through an opening of the pars flaccida, and their motion was measured
      in the direction in line with the stapes piston-like motion using a laser
      interferometer. When referencing the ossicular motion to EC pressure, an
      additional amplitude loss was found in reverse transmission compared to the gain
      in forward transmission, similar to previous findings relating intracochlear and
      EC pressure. In contrast, sound transmission along the ossicular chain was quite
      similar in forward and reverse directions. The difference in middle ear
      transmission in forward and reverse directions is most likely due to the
      different load impedances-the cochlea in forward transmission and the EC in
      reverse transmission.

PMID- 22466075
TI  - Mast cells and intestinal motility disorders (mastocytic enteritis/colitis).

PMID- 22466076
TI  - Intestinal epithelial cells with impaired autophagy lose their adhesive capacity
      in the presence of TNF-alpha.
AB  - BACKGROUND AND OBJECTIVES: Genome-wide association studies have revealed a link
      between autophagy-related (ATG) genes and susceptibility to Crohn's disease. This
      suggests underlying involvement of autophagy impairment in the pathogenesis of
      Crohn's disease. This study was performed to investigate the pathophysiological
      importance of autophagy impairment in intestinal epithelial cells exposed to TNF
      alpha. METHODS: Human colonic epithelial cells (HT-29) and rat small intestinal
      epithelial cells (IEC-18) were used. Formation of phosphatidylethanolamine
      conjugated microtubule-associated protein light chain 3 (LC3-II) was monitored as
      a marker of autophagy. Autophagy was inhibited using 3-methyladenine or short
      interfering RNA targeting ATG5 and ATG16L1. RESULTS: TNF-alpha treatment elicited
      a significant dose-dependent increase in LC3-II protein levels, thus autophagy is
      induced in the presence of TNF-alpha. Combined autophagy inhibition and TNF-alpha
      treatment induced a marked increase in the number of detached cells and a
      decrease in activated integrin beta1 protein levels. Trypan blue staining
      indicated 70-80 % of the detached cells were alive, suggesting that these cells
      became detached not because they were killed but because of dysfunction of
      cellular adhesion. CONCLUSIONS: This is the first study indicating that
      intestinal epithelial cells with impaired autophagy lose their adhesive capacity
      in the presence of TNF-alpha. These observations indicate that impairment of
      autophagy leads to disruption of the intestinal epithelial cell layers in TNF
      alpha-rich environments.

PMID- 22466077
TI  - Undertreatment of Asian chronic hepatitis B patients on the basis of standard
      guidelines: a community-based study.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have found that a major proportion of
      patients with chronic hepatitis B (CHB) do not receive antiviral therapy. The
      objective of this study was to characterize treatment eligibility on the basis of
      current guidelines, determine whether eligible patients actually receive
      treatment, and examine associated predictors. METHODS: We conducted a
      retrospective study of patients who were evaluated for CHB at two community
      gastroenterology clinics between April 2007 and February 2009. Using criteria
      published by the American Association for the Study of Liver Diseases (AASLD) in
      2007-2009 and by a panel of US hepatologists (US Panel) in 2006-2008, treatment
      eligibility was determined for the patients. RESULTS: Of 612 consecutive CHB
      patients included, mean age was 44 +/- 13 years, 54 % were male, and 99 % were
      Asian. Half (51 %) were eligible for treatment on the basis of the US Panel
      algorithm and 47 % of these patients also met AASLD treatment criteria. Overall,
      antiviral therapy was initiated for 50 % of eligible patients: 72 % of AASLD
      eligible patients and 29 % of patients who were US Panel-eligible only.
      Independent predictors for actual treatment initiation were higher ALT for AASLD
      eligible patients and higher ALT and older age for patients who were US Panel
      eligible only. The leading reasons for nontreatment were further observation
      recommended by the physician, followed by loss of follow-up and patient refusal.
      CONCLUSIONS: Approximately half of the CHB patients evaluated at community
      referral clinics met treatment criteria of at least one guideline; however, only
      about half received antiviral therapy within 12 months of presentation. Further
      studies are needed to optimize treatment of eligible CHB patients.

PMID- 22466079
TI  - Single-incision versus conventional laparoscopy for colorectal disease: a meta
      analysis.
AB  - BACKGROUND: Single-incision laparoscopic surgery (SILS) was developed as a novel
      minimally invasive surgical approach. AIMS: The aim of this meta-analysis was to
      compare SILS and conventional laparoscopy (CL) for colorectal diseases with
      respect to perioperative and oncologic outcomes. METHODS: An electronic search
      was performed to retrieve all relevant articles published in the English language
      between 2008 and 2012 comparing SILS and CL for colorectal diseases. The data
      were analyzed with fixed-effect or random-effects models using review manager
      version 5.0. RESULTS: A total of 14 studies (one randomized controlled trial and
      13 nonrandomized controlled trials) were found to be eligible and reported on
      1,155 subjects, of whom 521 underwent SILS and 634 underwent CL for colorectal
      diseases. Concerning the perioperative outcomes, no differences were observed in
      conversion rate, operating time, and postoperative adverse events; however,
      patients who underwent SILS had lower blood loss, decreased blood transfusion
      requirement, shorter time to flatus, shorter hospital stay, and smaller incision.
      Concerning the oncologic outcomes, length of resected specimens, number of
      harvested lymph nodes, proximal margin, and distal margin, were comparable
      between two groups. CONCLUSIONS: Single-incision laparoscopic surgery (SILS) is a
      safe, feasible, and oncological efficient alternative to CL for colorectal
      diseases. Further larger, multi-centred, randomised controlled trial is
      indicated.

PMID- 22466080
TI  - Pneumothorax following ERCP: report of four cases and review of the literature.
AB  - We report four patients with pneumothorax as a complication of ERCP with
      sphincterotomy. With conservative treatment all patients recovered. Previously,
      16 comparable cases have been reported in the literature. The main risk factor
      for this rare complication seems (pre-cut) sphincterotomy. Pneumothorax is
      usually right-sided or bilateral and accompanied by pneumomediastinum,
      pneumoretroperitoneum and subcutaneous emphysema. The prognosis seems favourable
      with a non-surgical approach including intravenous antibiotics, fasting and when
      indicated chest tube drainage.

PMID- 22466081
TI  - Xanthomatous tendinosis.
AB  - The patient was a 26-year-old man referred to a physical therapist for a chief
      complaint of worsening bilateral knee pain in the region of the patellar tendons
      over the past 3 months that was insidious in onset. In an effort to further
      evaluate tendon morphology, the physical therapist pursued ultrasound imaging of
      the bilateral patellar tendons. It was determined that the ultrasound findings
      were compatible with xanthomatous tendinosis.

PMID- 22466082
TI  - Synthesis and characterization of new Y-shaped fluorophores with an imidazole
      core.
AB  - Four new y-shaped fluorophores of 4- {4,5-[2,2'-Bis(2,4,6-trimethoxyphenyl)vinyl]
      1-H-imidazole-2-yl}benzonitrile 1a, 2-phenyl-{4,5-[2,2'-Bis(2,4,6
      trimethoxyphenyl)vinyl]-1-H-imidazole} 1b, 2- (9-anthryl)-{4,5-[2,2'-Bis(2,4,6
      trimethoxyphenyl)vinyl] }-1-H-imidazole 1c and 2- (4-nitrophenyl) - {4,5-[2,2'
      Bis(2,4,6-trimethoxyphenyl)vinyl] -1-H-imidazole 1d which bear an imidazole core,
      were synthesized for the first time via intermediate 1,6-Bis(2,4,6
      trimethoxyphenyl)hexa-1,5-diene-3,4-dion with different aldehydes. The structures
      of the new derivatives were confirmed by (1)H NMR, (13)C NMR and FT-IR. The
      optical properties such as absorption and emission maxima, Stokes' shift and
      quantum yield values were investigated in solvents of toluene, tetrahydrofuran
      and acetonitrile. The products show intense emission maxima in the range of 440
      630 nm. The imidazole derivatives exhibited excellent photostabilities.

PMID- 22466083
TI  - Isoprenoid biosynthesis in bacterial pathogens.
AB  - Isoprenoid biosynthesis is essential for cell survival. Over 35 000 isoprenoid
      molecules have been identified to date in the three domains of life (bacteria,
      archaea and eukaryotes), and these molecules are involved in a wide variety of
      vital biological functions. Isoprenoids may be synthesized via one of two
      independent nonhomologous pathways, the classical mevalonate pathway or the
      alternative 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Given that
      isoprenoids are indispensable, enzymes involved in their production have been
      investigated as potential drug targets. It has also been observed that the MEP
      pathway intermediate 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMB-PP) can
      activate human Vgamma9/Vdelta2 T cells. Herein we review isoprenoid biosynthesis
      in bacterial pathogens. The role of isoprenoid biosynthesis pathways in host
      pathogen interactions (virulence potential and immune stimulation) is examined.
      Finally, the design of antimicrobial drugs that target isoprenoid biosynthesis
      pathways is discussed.

PMID- 22466084
TI  - Naive Bayes QSDR classification based on spiral-graph Shannon entropies for
      protein biomarkers in human colon cancer.
AB  - Fast cancer diagnosis represents a real necessity in applied medicine due to the
      importance of this disease. Thus, theoretical models can help as prediction
      tools. Graph theory representation is one option because it permits us to
      numerically describe any real system such as the protein macromolecules by
      transforming real properties into molecular graph topological indices. This study
      proposes a new classification model for proteins linked with human colon cancer
      by using spiral graph topological indices of protein amino acid sequences. The
      best quantitative structure-disease relationship model is based on eleven Shannon
      entropy indices. It was obtained with the Naive Bayes method and shows excellent
      predictive ability (90.92%) for new proteins linked with this type of cancer. The
      statistical analysis confirms that this model allows diagnosing the absence of
      human colon cancer obtaining an area under receiver operating characteristic of
      0.91. The methodology presented can be used for any type of sequential
      information such as any protein and nucleic acid sequence.

PMID- 22466085
TI  - High prevalence of high grade anal intraepithelial neoplasia in HIV-infected
      women screened for anal cancer.
AB  - There is no consensus on optimal screening for anal cancer (AC) in HIV+ women.
      Seven hundred fifteen unique asymptomatic women in a high-prevalence HIV+
      community were screened for AC with anal cytology and triage to high-resolution
      anoscopy after routine screening was implemented in a large urban hospital
      system. Of these, 75 (10.5%) had an abnormal anal cytology and 29 (38.7%) of
      those with an abnormality had high-grade anal intraepithelial neoplasia (AIN).
      Women with poorly controlled HIV were significantly more likely to have high
      grade AIN (P = 0.03). Given the high rate of AIN in screened HIV-infected women,
      routine AC screening in all HIV-infected women should be strongly considered.

PMID- 22466086
TI  - Genetic background and 227Thorium as risk factors in biologically based models
      for induction of bone cancer in mice.
AB  - We explore the potential for the biologically based two-stage clonal expansion
      model to make statements about the influence of genetic factors on the steps in
      the model. We find evidence that the different susceptibility of BALB/C and
      CBA/Ca mice to bone cancer after (227)Thorium injection may be mostly due to
      different promotional responses to radiation. In BALB/C * CBA/Ca back-crossed
      mice, we analyzed the specific contribution of two individual loci in the
      carcinogenic process. This analysis suggests that the two high- or low-risk
      alleles are acting on promotion or on the background parameters, but not on
      radiation-induced initiation. Taken together with the comparison of CBA/Ca and
      BALB/C mice, this hints at the possibility that the two loci are candidates for
      modifying radiation-induced promotion.

PMID- 22466087
TI  - Review: limited evidence suggests that life skills programmes are no more
      effective than standard care or support groups for rehabilitation in chronic
      mental illnesses.

PMID- 22466089
TI  - Drug Discoveries & Therapeutics: A platform for promoting pharmaceutical sciences
      and clinical therapeutics.

PMID- 22466088
TI  - Delusional-like experiences are more common in those with cannabis dependence
      disorder, very early-onset alcohol use or dependence disorders, and daily
      smokers.

PMID- 22466090
TI  - c-Met: A potential therapeutic target for hepatocellular carcinoma.
AB  - The approval of receptor tyrosine kinase (RTK) targeted agent sorafenib as the
      first effective drug for the systemic treatment of advanced hepatocellular
      carcinoma (HCC) represents a milestone in the treatment of this disease. A better
      understanding of HCC pathogenesis will lead to development of novel targeted
      treatments. As a typical member of the RTK family, c-Met represents an intriguing
      target for cancer therapy. The c-Met signaling pathway has been shown to be
      deregulated and to correlate with poor prognosis in a number of major human
      cancers. This review discusses the possibility of c-Met as a target in HCC
      treatment from the following respects: i) c-Met expression and activation profile
      in HCC, ii) relationship between c-Met and clinicopathologic state and prognosis
      of HCC, iii) role of c-Met signaling activity in HCC genesis and progression, and
      iv) strategy of c-Met pathway targeting therapy in HCC treatment.

PMID- 22466091
TI  - Antibacterial activities of Sesbania grandiflora extracts.
AB  - In this study, Sesbania grandiflora, a plant in the Leguminosae family, was
      investigated for its antibacterial activities. The agar well diffusion assay as
      well as the agar and broth dilution assays were used for determination of
      antibacterial activities. The crude ethanolic extracts obtained from different
      parts of this plant exhibited different potent activities. The stem bark has the
      most potential to yield an extract with the highest antibacterial action. The
      fractionation of the stem bark with different solvents indicated that the
      fractionated extracts obtained from ethyl acetate or butanol possessed the most
      pronounced antibacterial activity. The kinetic study of bactericidal activities
      revealed that the butanol fractionated extract of the stem bark was effective
      against Gram negative bacteria. This study suggests that the stem bark of S.
      grandiflora contains promising antibacterial substances for clinical purposes.

PMID- 22466092
TI  - Purification of innate immunostimulant from green tea using a silkworm muscle
      contraction assay.
AB  - A polysaccharide was purified from a hot water extract of green tea leaves by
      measuring the immunostimulatory activity in silkworm larvae. Nuclear magnetic
      resonance and chemical analysis of acid hydrolysates revealed that the purified
      substance possessed a backbone containing polygalacturonic acids with methyl
      ester residues. Treatment with beta-glucanase attenuated the muscle contraction
      activity of the purified sample, suggesting that the beta-glucan structure,
      probably as a branched form, was required for its activity. The purified fraction
      stimulated the production of interleukin-6 by mouse peritoneal macrophages. These
      results suggest that measuring immunostimulation in silkworm larvae is useful for
      evaluating innate immunostimulants from various sources.

PMID- 22466093
TI  - Anti-influenza viral effects of novel nuclear export inhibitors from Valerianae
      Radix and Alpinia galanga.
AB  - Many pathogenic viruses, such as the influenza virus and the Human
      Immunodeficiency Virus (HIV)-1, are a threat to humans, thus leading to thousands
      of deaths annually. The development of antiviral drugs is urgent, and it is an
      essential strategy for the suppression of these infectious diseases. However,
      regardless of the rapid emergence of many infectious diseases, the development of
      novel antiviral drugs has been slow, except for the case of the AIDS. In
      addition, several viruses can easily mutate and escape the inhibitory activity of
      anti-viral drugs. It was already well-established that HIV escapes from anti
      viral drug effects because of the lack of proofreading activity in its reverse
      transcriptase. It is known that the influenza virus, which is resistant to
      Tamiflu, is already spread all over the world. Viruses utilize the host cell
      environment and cellular factors to propagate. Therefore, the development of
      novel drugs which inhibit viral protein-host protein interactions or cellular
      functions appear to be good candidates. The influenza virus is unique in
      replicating in host nuclei, and we therefore focused on the nuclear export
      processes for the development of anti-influenza viral drugs. We previously
      reported that leptomycin B (LMB), which inhibited the nuclear export processes
      via the nuclear export signal (NES) inhibited the nuclear export of influenza
      viral RNP (vRNP), and resulted in the inhibition of influenza viral propagation.
      We herein examined novel CRM1 inhibitors, valtrate from Valerianae Radix, and 1'
      acetoxychavicol acetate (ACA) from Alpinia galanga as potent inhibitors for the
      influenza virus replication.

PMID- 22466094
TI  - A comparative study of protective mechanisms of glycine and L-arginine against
      cisplatin-induced nephrotoxicity in rat renal cortical slices.
AB  - Amino acids exert nephroprotective effects in various forms of acute renal injury
      depending on their renal hemodynamic effects. The present study was designed to
      elucidate and compare the role of non hemodynamic mechanisms in protective
      actions afforded by glycine and L-arginine against cisplatin (CDDP)-induced
      nephrotoxicity using rat renal cortical slices (RCS). We have investigated the
      possible modulatory effect of glycine and L-arginine on oxidative stress and
      necrosis induced by CDDP as well as on CDDP uptake by kidney. After 4 h of
      incubation with 2 mM CDDP, nephrotoxicity was demonstrated by significant
      increased lactate dehydrogenase leakage, decreased ability of the slices to
      reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, increased
      lipid peroxides and depleted reduced glutathione. Also, CDDP significantly
      inhibited pyruvate-stimulated gluconeogenesis. Histopathological examination of
      RCS confirmed the occurrence of tubular coagulative necrosis in cortex and
      corticomedullary regions. Preincubation of RCS with 1 mM glycine or L-arginine 1
      h before CDDP addition significantly attenuated the oxidative stress and tubular
      necrotic effects of CDDP. L-Arginine showed greater antioxidant properties while
      glycine showed a greater antinecrotic effect. Moreover, the nephroprotective
      effect was mediated through lowering the platinum uptake by RCS. However, they
      could not counteract the inhibition of gluconeogenesis induced by CDDP. In
      conclusion, the present study sheds light on the mechanisms involved in glycine
      and L-arginine nephroprotection.

PMID- 22466095
TI  - Validated spectrophotometric methods for determination of some oral hypoglycemic
      drugs.
AB  - Four accurate, precise, rapid, reproducible, and simple spectrophotometric
      methods were validated for determination of repaglinide (RPG), pioglitazone
      hydrochloride (PGL) and rosiglitazone maleate (RGL). The first two methods were
      based on the formation of a charge-transfer purple-colored complex of chloranilic
      acid with RPG and RGL with a molar absorptivity 1.23 * 10<sup>3</sup> and 8.67 *
      10<sup>2</sup> l*mol<sup>-1</sup>*cm<sup>-1</sup> and a Sandell's sensitivity of
      0.367 and 0.412 MUg*cm<sup>-2</sup>, respectively, and an ion-pair yellow-colored
      complex of bromophenol blue with RPG, PGL and RGL with molar absorptivity 8.86 *
      10<sup>3</sup>, 6.95 * 10<sup>3</sup>, and 7.06 * 10<sup>3</sup> l*mol<sup>
      1</sup>*cm<sup>-1</sup>, respectively, and a Sandell's sensitivity of 0.051
      MUg*cm<sup>-2</sup> for all ion-pair complexes. The influence of different
      parameters on color formation was studied to determine optimum conditions for the
      visible spectrophotometric methods. The other spectrophotometric methods were
      adopted for demtermination of the studied drugs in the presence of their acid-,
      alkaline- and oxidative-degradates by computing derivative and pH-induced
      difference spectrophotometry, as stability-indicating techniques. All the
      proposed methods were validated according to the International Conference on
      Harmonization guidelines and successfully applied for determination of the
      studied drugs in pure form and in pharmaceutical preparations with good
      extraction recovery ranges between 98.7-101.4%, 98.2-101.3%, and 99.9-101.4% for
      RPG, PGL, and RGL, respectively. Results of relative standard deviations did not
      exceed 1.6%, indicating that the proposed methods having good repeatability and
      reproducibility. All the obtained results were statistically compared to the
      official method used for RPG analysis and the manufacturers methods used for PGL
      and RGL analysis, respectively, where no significant differences were found.

PMID- 22466096
TI  - Matrix type transdermal therapeutic systems of glibenclamide: Formulation, ex
      vivo and in vivo characterization.
AB  - Matrix type transdermal therapeutic systems (TTS) of glibenclamide were
      formulated using polymers Eudragit RL 100, ethyl cellulose, PVP K-30, and
      polyvinyl acetate, and citral was used as the penetration enhancer. The polymer
      films were formulated with Eudragit RL 100 and PVP K-30 in different ratios and
      subsequently subjected to ex vivo studies (drug permeation through rat skin)
      followed by interaction studies, skin irritation studies, accelerated stability
      analysis, and in vivo studies (determination of blood glucose level in rabbits).
      The drug content of the formulations was found to be 99.1-99.2%. The cumulative
      percentages of drug permeated through rat skin from the three selected
      formulations in 48 h were 95.3%, 98.8%, and 99%, respectively. A plot between
      cumulative percent of drug permeated and square root of time exhibited linear
      curves, which suggests the Higuchian matrix mechanism of drug release. The
      formulation containing Eudragit RL 100 and PVP K-30 showed better improvement in
      hypoglycemic activity in rabbits (56.2-60.8% reduction in blood glucose level, p
      < 0.05). There were fewer fluctuations in blood glucose level as compared to oral
      therapy due to controlled release of the active pharmaceutical ingredient, and no
      interaction was found between the drug and excipients of the formulation.
      Accelerated stability analysis showed that the formulation was stable up to 5.5
      years, with negligible skin irritation. The formulation precluded severe
      hypoglycemic reactions (side effect of sulfonylureas) and was effective for
      management of diabetes mellitus up to 48 h, with a single TTS.

PMID- 22466097
TI  - Liquid water simulations with the density fragment interaction approach.
AB  - We reformulate the density fragment interaction (DFI) approach [Fujimoto and
      Yang, J. Chem. Phys., 2008, 129, 054102.] to achieve linear-scaling quantum
      mechanical calculations for large molecular systems. Two key approximations are
      developed to improve the efficiency of the DFI approach and thus enable the
      calculations for large molecules: the electrostatic interactions between
      fragments are computed efficiently by means of polarizable electrostatic
      potential-fitted atomic charges; and frozen fragment pseudopotentials, similar to
      the effective fragment potentials that can be fitted from interactions between
      small molecules, are employed to take into account the Pauli repulsion effect
      among fragments. Our reformulated and parallelized DFI method demonstrates
      excellent parallel performance based on the benchmarks for the system of 256
      water molecules. Molecular dynamics simulations for the structural properties of
      liquid water also show a qualitatively good agreement with experimental
      measurements including the heat capacity, binding energy per water molecule, and
      the radial distribution functions of atomic pairs of O-O, O-H, and H-H. With this
      approach, large-scale quantum mechanical simulations for water and other liquids
      become feasible.

PMID- 22466098
TI  - Inhibition of Pim-1 kinase ameliorates dextran sodium sulfate-induced colitis in
      mice.
AB  - BACKGROUND: Pim-1 kinase is involved in the control of cell growth,
      differentiation and apoptosis. Recent evidence suggests that Pim kinases play a
      role in immune regulation and inflammation. However, the role of Pim-1 kinase in
      inflammatory bowel diseases (IBD) remains unclear. AIMS: The aims of this study
      were to explore the role of Pim-1 kinase in the pathology of IBD and to assess
      whether inhibiting Pim-1 kinase may be of therapeutic benefit as a treatment
      regimen for IBD. METHODS: Colitic mouse model was established by the induction of
      dextran sodium sulfate. The expression of Pim-1 in the colonic samples of control
      and colitic mice was examined. Furthermore, the mice were treated with Pim
      1inhibitor (PIM-Inh), then the body weight and colon inflammation were evaluated,
      and the production of cytokines including IFN-gamma, IL-4, TGF-beta and IL-17 in
      colon tissues was determined by ELISA. The expression of T cell master
      transcription factors T-bet, ROR-gammat, GATA-3 and Foxp3 and Nuclear factor
      kappaB (NF-kappaB) and inducible nitric oxide synthase in colon tissues was
      detected by real-time PCR and western blot. Finally, the effect of LPS on Pim-1
      expression and the effects of PIM-Inh on LPS-induced upregualtion of p65 and TNF
      alpha in RAW264.7 cells were examined by real-time PCR and western blot. RESULTS:
      Pim-1 expression was correlated with the degree of mucosal inflammation in vivo,
      and it was significantly induced by LPS in vitro. PIM-Inh had protective effects
      on acute colitis in vivo. Mechanistically, PIM-Inh reduced the proinflammatory
      immune response through the inhibition of the overactivation of macrophages and
      the down-regulation of excessive Th1- and Th17-type immune responses.
      Furthermore, PIM-Inh could skew T cell differentiation towards a Treg phenotype.
      CONCLUSIONS: Pim-1 kinase is involved in mucosal injury/inflammation and Pim-1
      kinase inhibitor may provide a novel therapeutic approach for IBD.

PMID- 22466099
TI  - Changing epidemiology of colorectal cancer makes screening sigmoidoscopy less
      useful for identifying carriers of colorectal neoplasms.
AB  - BACKGROUND: There is renewed interest in flexible sigmoidoscopy (FS) colorectal
      cancer (CRC) screening following trials showing significantly reduced CRC
      incidence and mortality. AIMS: To evaluate the potential usefulness of FS
      screening in our population. METHODS: We examined rectosigmoid (RS) cancer
      epidemiology in our Jewish population using Israel National Cancer Registry data,
      computed by CRC site, age groups, and gender. We also reviewed endoscopy
      screening publications for prevalence of RS and proximal advanced adenomas (AAP)
      and having both or either. RESULTS: During 1980-2008, there were 64,559 CRCs
      registered; 31.6 % were RS cancer which has now decreased to 29 % of men's and 26
      % of women's CRC (both P < 0.01). In <50 year olds, RS cancer occurred in 42 % of
      males' and 35 % of females' CRC, and in the last 2 decades this ratio is
      unchanged. In 50-74 year olds, RS cancer decreased to stable levels of 32 % of
      males' and 29 % females' CRC (both P < 0.01). In >=75 year olds, RS cancer
      progressively decreased to 24 % of males' and 22 % females' CRC (both P < 0.001).
      From endoscopy screening reports in 40-79 year olds, RS AAPs occurred in 2.0-5.8
      %, being least in women, most in men, and not increased with aging. Some 50-57 %
      of screenees had both RS and proximal AAPs, least when aged 40-49 years at 25 %,
      women were 35 %, and with aging 40 %, but most in men at 70 %. CONCLUSIONS: With
      the changing CRC epidemiology, having fewer RS neoplasms but more proximal
      cancer, the effectiveness of FS screening for identifying significant neoplasms
      decreases with screenees' age and especially in females. These make FS screening
      less suitable for our aging and increasingly female population.

PMID- 22466100
TI  - Evaluation of early atherosclerosis in patients with inflammatory bowel disease.
AB  - BACKGROUND: Data regarding early atherosclerosis and inflammatory bowel disease
      are limited and conflicting results are present. AIMS: The purpose of this study
      was to evaluate serological and sonographical evidence of subclinical vascular
      involvement in patients with inflammatory bowel disease. METHODS: Thirty-nine
      patients with inflammatory bowel disease (20 Crohn's disease, and 19 ulcerative
      colitis patients) and 31 healthy controls were consecutively enrolled in the
      study. Flow mediated dilatation of the brachial artery and intima media thickness
      assessments of the common carotid artery were measured sonographically. Soluble
      CD40 ligand levels were evaluated. Crohn's disease activity index and modified
      Truelove-Witt's criteria were also noted. RESULTS: Age, sex distribution, serum
      lipids, smoking status, and intima media thickness of the common carotid artery
      were similar between the inflammatory bowel disease patients and controls (p >
      0.05). However, both endothelium dependent and independent flow mediated
      dilatation values were significantly impaired in the inflammatory bowel disease
      group compared with healthy controls (p < 0.05). Erythrocyte sedimentation rate,
      C-reactive protein and soluble CD40 ligand values were significantly increased in
      inflammatory bowel disease patients compared with controls (p < 0.05), and
      soluble CD40 ligand was negatively correlated with flow mediated dilatation (r = 
      0.3, p < 0.05). Flow mediated dilatation was significantly predicted from the
      concentrations of C-reactive protein and soluble CD40 ligand. CONCLUSION:
      Functional atherosclerosis is present in inflammatory bowel disease before early
      structural changes occur in vasculature. Higher sCD40L may indicate worse
      vascular outcome for IBD.

PMID- 22466101
TI  - OCT assessment of tear meniscus after punctal occlusion in dry eye disease.
AB  - PURPOSE: To evaluate the tear meniscus changes after punctal occlusion in dry eye
      patients using Visante optical coherence tomography (OCT) in a prospective
      controlled study. METHODS: Thirty eyes of 15 symptomatic dry eye patients not
      responding to non-preserved artificial tears received additional upper and lower
      punctal occlusion with silicone plugs, and 30 eyes of 15 age- and sex-matched dry
      eye control patients received only non-preserved artificial tears treatment for 1
      month. All subjects underwent tear meniscus height (TMH) measurements with
      Visante OCT. All study participants also underwent slitmicroscopy graticule scale
      TMH measurement, strip meniscometry testing, tear film break-up time measurement,
      ocular surface vital staining with fluorescein and Rose Bengal dyes, and the
      Schirmer-1 test. Both groups, dry eye and control group patients, were examined
      before and after 1-month treatment. Wilcoxon-matched pair test was performed. The
      study was conducted in compliance with the Tenets of the Declaration of Helsinki.
      RESULTS: TMH measurements by OCT and slitlamp graticule scale significantly
      improved after punctal occlusion (p < 0.001) and remain unchanged in the dry eye
      control patients. Similarly, strip meniscometry scores, mean tear stability
      values, Rose Bengal, and fluorescein staining scores showed significant
      improvement after punctal occlusion (p < 0.05). Schirmer-1 test values tended to
      be higher after 1 month of treatment in both groups without any statistical
      significance (p > 0.05). CONCLUSIONS: OCT TMH measurement appears to be effective
      in monitoring tear meniscus changes after punctal occlusion. OCT can be a
      valuable non-invasive and quick clinical tool for evaluation of treatment
      responses in dry eye patients.

PMID- 22466102
TI  - Foveal localization in non-exudative AMD using scanning laser polarimetry.
AB  - PURPOSE: To determine whether custom scanning laser polarimetry (SLP) images,
      differing in polarization content, can be used to accurately localize the fovea
      in the presence of non-exudative age-related macular degeneration (AMD). To
      determine whether alterations to the foveal structure in non-exudative AMD
      significantly disrupts the birefringent Henle fiber layer, responsible for the
      macular cross pattern in some SLP images. To determine whether phase retardation
      information, specifically color-coded information representing its magnitude and
      axis, allow better foveal localization than images including retardation
      amplitude only. METHODS: SLP images were acquired in 25 AMD subjects and 25 age
      matched controls. Raw data were used to generate five custom image types
      differing in polarization content. The foveal location was marked by three
      graders in each image type for each subject. The difference in variability was
      compared between the AMD subjects and matched controls. We further determined
      whether the orientation of Henle fiber layer phase retardation improved
      localization in 10 subjects with the highest variability in images including only
      phase retardation amplitude. RESULTS: Images that differed in polarization
      content led to strikingly different visualizations of AMD pathology. The Henle
      fiber layer remained sufficiently intact to assist in fovea localization in all
      subjects but with more variability in the AMD group. For both the AMD and matched
      control group, images containing birefringence amplitude and orientation
      information reduced the amount of intragrader, intergrader, and interimage
      variability for estimating foveal location. CONCLUSIONS: The disruption in Henle
      fiber birefringence was evident in the eyes with AMD but nevertheless was
      sufficient to help in foveal localization despite macular pathology. Phase
      retardation amplitude and axis of orientation can be a useful tool in foveal
      localization in patients with AMD.

PMID- 22466103
TI  - Future directions in non-invasive measurements of tear film surface kinetics.
AB  - PURPOSE: To review the methods for dynamic, non-invasive, and objective
      assessment of tear film surface quality and to outline their current state-of-the
      art and their future potential. METHODS: Among the methods available, high-speed
      videokeratoscopy, lateral shearing interferometry, and dynamic wavefront sensing
      are being considered. RESULTS: The principles of operations, their advantages and
      disadvantages, and limitations of each method are being outlined. The possible
      future directions of each method are also discussed. CONCLUSIONS: To gain a
      better understanding of tear film, its structure and function, it is essential to
      combine macroimaging technologies with those focusing on tear film
      microstructure. In this way, one can envisage a clinical device that could help,
      in future, early diagnosis of dry eye syndrome and development of better
      materials for contact lenses and eye lubricants.

PMID- 22466104
TI  - A method for profiling biometric changes during disaccommodation.
AB  - PURPOSE: To demonstrate the application of low-coherence reflectometry to the
      study of biometric changes during disaccommodation responses in human eyes after
      cessation of a near task and to evaluate the effect of contact lenses on low
      coherence reflectometry biometric measurements. METHODS: Ocular biometric
      parameters of crystalline lens thickness (LT) and anterior chamber depth (ACD)
      were measured with the LenStar device during and immediately after a 5 D
      accommodative task in 10 participants. In a separate trial, accommodation
      responses were recorded with a Shin-Nippon WAM-5500 optometer in a subset of two
      participants. Biometric data were interleaved to form a profile of post-task
      anterior segment changes. In a further experiment, the effect of soft contact
      lenses on LenStar measurements was evaluated in 15 participants. RESULTS: In 10
      adult participants, increased LT and reduced ACD was seen during the 5 D task.
      Post-task, during fixation of a 0 D target, a profile of the change in LT and ACD
      against time was observed. In the two participants with accommodation data (one a
      sufferer of nearwork-induced transient myopia and other a non-sufferer), the post
      task changes in refraction compared favorably with the interleaved LenStar
      biometry data. The insertion of soft contact lenses did not have a significant
      effect on LenStar measures of ACD or LT (mean change: -0.007 mm, p = 0.265 and +
      0.001 mm, p = 0.875, respectively). CONCLUSIONS: With the addition of a
      relatively simple stimulus modification, the LenStar instrument can be used to
      produce a profile of post-task changes in LT and ACD. The spatial and temporal
      resolution of the system is sufficient for the investigation of nearwork-induced
      transient myopia from a biometric viewpoint. LenStar measurements of ACD and LT
      remain valid after the fitting of soft contact lenses.

PMID- 22466105
TI  - Distortion correction of OCT images of the crystalline lens: gradient index
      approach.
AB  - PURPOSE: To propose a method to correct optical coherence tomography (OCT) images
      of posterior surface of the crystalline lens incorporating its gradient index
      (GRIN) distribution and explore its possibilities for posterior surface shape
      reconstruction in comparison to existing methods of correction. METHODS: Two
      dimensional images of nine human lenses were obtained with a time-domain OCT
      system. The shape of the posterior lens surface was corrected using the proposed
      iterative correction method. The parameters defining the GRIN distribution used
      for the correction were taken from a previous publication. The results of
      correction were evaluated relative to the nominal surface shape (accessible in
      vitro) and compared with the performance of two other existing methods (simple
      division, refraction correction: assuming a homogeneous index). Comparisons were
      made in terms of posterior surface radius, conic constant, root mean square, peak
      to valley, and lens thickness shifts from the nominal data. RESULTS: Differences
      in the retrieved radius and conic constant were not statistically significant
      across methods. However, GRIN distortion correction with optimal shape GRIN
      parameters provided more accurate estimates of the posterior lens surface in
      terms of root mean square and peak values, with errors <6 and 13 MUm,
      respectively, on average. Thickness was also more accurately estimated with the
      new method, with a mean discrepancy of 8 MUm. CONCLUSIONS: The posterior surface
      of the crystalline lens and lens thickness can be accurately reconstructed from
      OCT images, with the accuracy improving with an accurate model of the GRIN
      distribution. The algorithm can be used to improve quantitative knowledge of the
      crystalline lens from OCT imaging in vivo. Although the improvements over other
      methods are modest in two dimension, it is expected that three-dimensional
      imaging will fully exploit the potential of the technique. The method will also
      benefit from increasing experimental data of GRIN distribution in the lens of
      larger populations.

PMID- 22466106
TI  - Floating gallbladder strangulation caused by the lesser omentum: report of a
      case.
AB  - Strangulation of the gallbladder by the omentum is extremely rare. We report what
      to our knowledge is only the second documented case of strangulation of a
      floating gallbladder by the lesser omentum. A 61-year-old Japanese woman
      presented to a local hospital after the sudden onset right upper quadrant pain.
      Her clinical features suggested a gallbladder volvulus, and the patient was
      referred to our hospital for investigation and treatment. Ultrasonography and
      computed tomography showed no cholecystolithiasis, but the fundus and body of the
      gallbladder were markedly swollen without wall thickening, whereas the neck of
      the gallbladder was normal. A narrowed, twisted area was seen between the body
      and neck of the gallbladder. Based on these findings, gallbladder volvulus was
      diagnosed and she underwent emergency laparoscopic cholecystectomy. The fundus
      and body of the gallbladder were grossly necrotic. The narrowest part of the
      gallbladder was tightly strangulated by the lesser omentum, but the gallbladder
      neck was normal. Histopathologic examination of the resected gallbladder showed
      ischemic changes in the wall of the fundus and body. This case highlights that
      the clinical features and imaging findings of a gallbladder strangulated by the
      lesser omentum are similar to those of gallbladder volvulus and that a positive
      outcome is dependent on a correct diagnosis and prompt surgical management.

PMID- 22466107
TI  - Mapping the intracellular distribution of carbon nanotubes after targeted
      delivery to carcinoma cells using confocal Raman imaging as a label-free
      technique.
AB  - The uptake of carbon nanotubes (CNTs) by mammalian cells and their distribution
      within cells is being widely studied in recent years due to their increasing use
      for biomedical purposes. The two main imaging techniques used are confocal
      fluorescence microscopy and transmission electron microscopy (TEM). The former,
      however, requires labeling of the CNTs with fluorescent dyes, while the latter is
      a work-intensive technique that is unsuitable for in situ bio-imaging. Raman
      spectroscopy, on the other hand, presents a direct, straightforward and label
      free alternative. Confocal Raman microscopy can be used to image the CNTs inside
      cells, exploiting the strong Raman signal connected to different vibrational
      modes of the nanotubes. In addition, cellular components, such as the endoplasmic
      reticulum and the nucleus, can be mapped. We first validate our method by showing
      that only when using the CNTs' G band for intracellular mapping accurate results
      can be obtained, as mapping of the radial breathing mode (RBM) only shows a small
      fraction of CNTs. We then take a closer look at the exact localization of the
      nanotubes inside cells after folate receptor-mediated endocytosis and show that,
      after 8-10 h incubation, the majority of CNTs are localized around the nucleus.
      In summary, Raman imaging has enormous potential for imaging CNTs inside cells,
      which is yet to be fully realized.

PMID- 22466108
TI  - Dorsal triquetrum fracture.
AB  - The patient was a 39-year-old man who self-referred to a physical therapist with
      a chief complaint of right wrist pain after falling backward onto an outstretched
      right hand the previous day. Based on the suspicion of a fracture, right wrist
      radiographs (posterior-to-anterior, lateral, and oblique views) were completed,
      which revealed a comminuted dorsal triquetrum fracture. The patient was referred
      to an orthopaedic surgeon who recommended nonoperative management.

PMID- 22466109
TI  - Laparoscopic treatment of left paraduodenal hernia in two cases of children.
AB  - INTRODUCTION: The paraduodenal hernia is an internal hernia that might cause a
      small bowel obstruction. The laparoscopic repair of paraduodenal hernia is
      sporadically reported for its safety, convenience, and patient's satisfaction.
      PRESENTATION OF CASE: We performed the laparoscopic treatment of the left
      paraduodenal hernia in two children, a 3-months old boy and 12-year old girl. The
      girl had a left upper quadrant pain for one month with postprandial nausea after
      eating. The 3-months boy presented with an intermittent severe irritability.
      Small bowel series and computed tomography showed the left paraduodenal hernia in
      two patients. We successfully did the laparoscopic paraduodenal hernia repair
      using 5mm and 3mm laparoscope. They discharged within 5days, uneventfully.
      DISCUSSION: Despite of technical difficulties in pediatrics such as small working
      space and less pneumoperitoneum, the laparoscopic repair for paraduodenal hernia
      leads to patient's earlier intake of diet and rapid recovery with cosmetic
      satisfaction. The 3mm laparoscopic repair needs longer operation time, but it is
      feasible in infants. CONCLUSION: Laparoscopic repair of paraduodenal hernia in
      children and infants is safe and feasible. We recommend the laparoscopic repair
      as the first surgical option for paraduodenal hernia.

PMID- 22466110
TI  - "Diamond" mammoplasty as a part of conservative management of breast cancer:
      Description of a new technique.
AB  - INTRODUCTION: Oncoplastic surgery is an integral part of current surgical
      treatment of breast cancer. Superior breast quadrant is a forgiving tumor
      location that often allows the conservation of the breast with simple
      mammoplastic manoeuvres. In this report, we describe a novel modification of the
      classic level I mammoplasty. PRESENTATION OF CASE: A 49 years patient had an ill
      defined carcinoma at the 12 o'clock position that necessitated a generous
      tumorectomy. A diamond shaped incision was done over the tumor area and the
      nipple-areola complex. Peri-areolar skin was de-epithelialized and the
      tumorectomy was completed down to the pectoral plane. The incision was closed in
      a star-like shape around the areola leading to natural appearance of the breast
      and a limited visible suture line. DISCUSSION: We suggest that the described
      technique offered an advantage over the classic omega mastopexy or the round
      block technique and provided a versatile technique for oncologic management and
      mastopexy. CONCLUSION: The presented technique may be considered when performing
      level I mammoplasty.

PMID- 22466111
TI  - Congenital band of the vitelline artery remnant as a cause of chronic lower
      abdominal pain in an adult: Case report.
AB  - INTRODUCTION: Intraabdominal bands of the vitelline vessel remnant are the rarest
      form of congenital mesodiverticluar bands which may or may not be associated with
      Meckel's diverticulum. In the majority of cases they cause an acute abdominal
      disease such as intestinal obstruction, especially in children. PRESENTATION OF
      CASE: We report a case of a 64 year old gentleman who experienced recurrent
      episodes of abdominal distension and bloating over two years. Computed tomography
      of his abdomen, colonoscopy, and barium follow through were all normal.
      Diagnostic laparoscopy revealed a single band adhesion stretching between the
      distal ileal mesentery and the anterior abdominal wall near the umbilicus.
      DISCUSSION: Congenital vascular bands are established causes of acute intestinal
      obstruction especially in children but are relatively uncommon. Their role in
      chronic abdominal pain is rare and diagnosis is difficult preoperatively. Pain in
      the patient was most likely due to recurrent partial twisting and untwisting of
      the bowel around the band. CONCLUSION: This case not only highlights an unusual
      cause of chronic abdominal pain, but also the effectiveness of laparoscopy as a
      diagnostic tool in such patients.

PMID- 22466112
TI  - Spontaneous bilateral compartment syndrome of the legs: A case report and review
      of the literature.
AB  - INTRODUCTION: Bilateral acute compartment syndrome of the legs is a rare
      presentation requiring emergent surgical intervention. PRESENTATION OF CASE: We
      report the case of 41-year-old woman who presented with acute bilateral
      compartment syndrome of the legs, complicated by rhabdomyolysis and acute renal
      failure. DISCUSSION: There are very few previously reported cases of bilateral
      compartment syndrome of the legs. In the present case, despite any clear
      causative factor, we suggest that the aetiology is related to inadvertent posture
      during sleep. CONCLUSION: The diagnosis of acute bilateral compartment syndrome
      of the legs requires a high index of suspicion, particularly in the absence of
      obvious aetiology. A successful outcome can be achieved with early diagnosis,
      prompt surgical intervention and a multidisciplinary approach.

PMID- 22466113
TI  - Intervertebral discitis caused by nontypeable Haemophilus influenzae in an adult:
      Case report.
AB  - INTRODUCTION: Haemophilus influenzae is a common cause of bacterial meningitis in
      children and can cause upper respiratory tract infections in adults, but has yet
      to be reported solely involving intervertebral discitis. PRESENTATION OF CASE: A
      67-year-old builder presenting with fever, myalgia and back pain is found to have
      intervertebral discitis (confirmed on MRI) caused by H. influenzae (identified on
      blood cultures). DISCUSSION: A nontypeable form of H. influenzae has not been
      reported causing discitis. We describe a case in a relatively fit individual who
      was treated successfully with antimicrobial treatment. A preceding upper
      respiratory tract infection is the presumed source of infection, predisposed by
      long-term low-dose steroid therapy. CONCLUSION: H. influenzae is a rare, but
      treatable cause of discitis.

PMID- 22466114
TI  - Metastatic Ewing's sarcoma/PNET of kidney in 40 year old patient.
AB  - INTRODUCTION: Primary renal Ewing sarcoma/PNET is an uncommon and very aggressive
      tumor. PRESENTATION OF CASE: : We report the case of a young woman who underwent
      nephrectomy for a renal mass from unknown etiology. Histologic analysis found
      small tumoral cells in rosette formation, and immunohistochemical staining was
      positive for CD99, and focally positive for vimentin and Protein S-100. A post
      operative abdominal computed tomography (CT) scan revealed a residual renal
      processus with hepatic wounds and abdominal metastatic nodes. After 6 cycles of
      chemotherapy including Vincristine, Doxorubicin, Cyclophosphamide, the response
      was considered as good. DISCUSSION: Ewing's sarcoma/PNET of kidney is a member of
      the family of small round cell tumors and it should be differentiated from Wilms
      tumor, neuroblastoma, rhabdomyosarcoma and lymphoblastic lymphoma. The principle
      management of its treatment have been extrapolated from the treatment of osseous
      Ewing sarcoma of bone. CONCLUSION: Despite aggressive treatment, primary renal
      Ewing sarcoma/PNET has a poor prognosis. It requires a multidisciplinary approach
      including oncologists, urologists and radiation oncologists.

PMID- 22466115
TI  - Unusual treatment of abdominal aortic aneurysm: Aortic stenting with covered
      stent.
AB  - INTRODUCTION: It is now becoming increasingly difficult to accept that some
      patients are not suitable for surgery due to high surgical risk. The continuous
      technological progress, in the endovascular field in particular, are urging
      surgeons to put the limit even more forth. PRESENTATION OF CASE: We are going to
      describe an endovascular option used to treat an infrarenal aortic aneurysm where
      the diameter of the iliac vessels couldn't allow the use of any device available
      on the market. Three covered AdvantaV12 stents were placed in series in the aorta
      to build the endoprosthesis body and two Bard Fluency 8mm*60mm were then placed
      in a "kissing way" into the common iliac arteries like legs. DISCUSSION:
      Continuous technological progress, particularly in the endovascular field, is
      driving surgeons to push the limits even further. Nevertheless, some things still
      seem not to be possible, but in comparison to traditional surgery where all is
      well demonstrated and documented, the endovascular approach is still a young
      discipline and allows us to try to find new solutions. CONCLUSION: We can
      therefore assert that in exceptional circumstances, an aortic endoprosthesis can
      be built inside the aortic lumen using covered stents.

PMID- 22466116
TI  - Spectrum of all-terrain vehicle injuries in adults: A case series and review of
      the literature.
AB  - INTRODUCTION: Serious injury secondary to all terrain vehicle usage has been
      widely reported since the 1970s. All-terrain vehicles (ATV) or 'quad bikes' are
      four wheeled vehicles used for agricultural work, recreation and adventure sport.
      Data collected in the U.S. indicates that ATV related injury and fatality is
      increasing annually. PRESENTATION OF CASES: This case series describes 3 cases of
      significant ATV related trauma in adults presenting to one regional hospital in
      the West of Ireland over a 12month period. DISCUSSION: Epidemiology, mechanisms
      of injury, spectrum of injury in adults and preventative measures to reduce the
      number of ATV related injuries and fatalities are discussed here with a review of
      the literature. CONCLUSION: A paucity of research outside of North America is
      highlighted by this case series. Mandatory reporting of ATV related injury,
      educational, training and legislative measures are suggested as injury prevention
      strategies.

PMID- 22466117
TI  - Positivity for anti-RNP antibody is a risk factor for adverse effects caused by
      trimethoprim-sulfamethoxazole, a prophylactic agent for P. jiroveci pneumonia, in
      patients with connective tissue diseases.
AB  - OBJECTIVES: Trimethoprim-sulphamethoxazole (TMP-STX), an agent used for
      prophylaxis against pneumocystis pneumonia (PCP) in immunocompromised hosts,
      causes serious adverse effects (AEs) in some patients. The objective of this
      study was to identify the risk factors for AEs caused by TMP-STX in connective
      tissue disease (CTD) patients and to describe the clinical features of the AEs.
      METHODS: The medical records of 539 patients (CTDs 312, pulmonary diseases 227)
      receiving TMP-STX for prophylaxis against PCP were reviewed retrospectively.
      Patients with human immunodeficiency virus were excluded. Univariate and
      multivariate analyses were conducted to identify the risk factors. RESULTS:
      Adverse events caused by TMP-STX occurred in 22 of 312 (7.05 %) CTD patients,
      while only six of 227 (2.64 %) pulmonary disease patients developed AEs. The
      incidence of AEs was significantly higher in systemic lupus erythematosus (SLE)
      (11.0 %) and mixed connective tissue disease (MCTD) (33.3 %) patients than in
      other CTD patients. AEs occurred in 25 % of patients with anti-RNP antibody.
      Univariate analysis revealed that SLE, MCTD, and anti-RNP antibody were risk
      factors for AEs in CTD patients. Further multivariate analyses demonstrated that
      only anti-RNP antibody positivity was a risk factor for AEs. Systemic
      inflammation, including fever, was a characteristic manifestation of the AEs in
      CTD patients, particularly those with anti-RNP antibody. CONCLUSIONS: Positivity
      for anti-RNP antibody is a risk factor for AEs caused by TMP-STX in CTD patients.
      Systemic inflammation, including fever, might be a characteristic feature of the
      AEs in CTD patients, particularly those with anti-RNP antibody.

PMID- 22466118
TI  - Analysis of the affected joints in rheumatoid arthritis patients in a large
      Japanese cohort.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder involving
      multiple joints. We investigated the distribution of the affected joints and the
      relationships among this distribution, the disease activity, and the disease
      duration in Japanese RA patients by cross-sectional analysis using the National
      Database of Rheumatic Diseases by iR-net in Japan. MATERIALS AND METHODS: A total
      of 6408 RA patients registered in the database were analyzed. In each patient,
      the location of joint swelling and joint tenderness of 68 joints was examined,
      and the relationships among the distribution of the affected joints, the disease
      activity as determined using the DAS28-ESR, and the disease duration were
      analyzed statistically. RESULTS: For the 6408 RA patients examined, the wrist was
      the most frequently affected site. There were some differences in the prevalence
      of tenderness and swelling; tenderness was frequently observed in large joints
      such as the knee, elbow and shoulder, while swelling was frequently observed in
      small joints such as the metacarpophalangeal joints. Although the frequency of
      involvement increased in all joints as disease activity increased, the pattern of
      distribution was not affected by disease activity. Furthermore, the distribution
      was not influenced by disease duration. CONCLUSIONS: Based on the results of this
      study, we can draw the following conclusions: (1) the wrist was the most affected
      joint; (2) there was a discrepancy between the distribution of swollen joints and
      that of tender joints; and (3) the distribution of affected joints was uniform
      regardless of disease activity.

PMID- 22466119
TI  - Photoinduced in situ generation of a DNA-binding benzothiazoloquinolinium
      derivative.
AB  - A styrylbenzothiazole substrate that has no significant affinity towards DNA was
      transformed photochemically into a DNA-binding benzothiazoloquinolinium ion. The
      photoreaction may be performed directly in the presence of DNA thus establishing
      the DNA-ligand interaction in situ with temporal control.

PMID- 22466120
TI  - Population coding of somatic sensations.
AB  - The somatic sensory system includes a variety of sensory modalities, such as
      touch, pain, itch, and temperature sensitivity. The coding of these modalities
      appears to be best explained by the population-coding theory, which is composed
      of the following features. First, an individual somatic sensory afferent is
      connected with a specific neural circuit or network (for simplicity, a sensory
      labeled line), whose isolated activation is sufficient to generate one specific
      sensation under normal conditions. Second, labeled lines are interconnected
      through local excitatory and inhibitory interneurons. As a result, activation of
      one labeled line could modulate, or provide gate control of, another labeled
      line. Third, most sensory fibers are polymodal, such that a given stimulus placed
      onto the skin often activates two or multiple sensory-labeled lines; crosstalk
      among them is needed to generate one dominant sensation. Fourth and under
      pathological conditions, a disruption of the antagonistic interaction among
      labeled lines could open normally masked neuronal pathways, and allow a given
      sensory stimulus to evoke a new sensation, such as pain evoked by innocuous
      mechanical or thermal stimuli and itch evoked by painful stimuli. As a result of
      this, some sensory fibers operate along distinct labeled lines under normal
      versus pathological conditions. Thus, a better understanding of the neural
      network underlying labeled line crosstalk may provide new strategies to treat
      chronic pain and itch.

PMID- 22466121
TI  - Peripheral mechanisms of itch.
AB  - Detection of environmental stimuli that provoke an aversive response has been
      shown to involve many receptors in the periphery. Probably the least-studied of
      these stimuli are those that induce the perception of itch (pruritus), an often
      experienced unpleasant stimulus. This review covers the ligands and their
      receptors which are known to cause primary sensory neuron activation and initiate
      itch sensation. Also covered are several itch-inducing substances which may act
      indirectly by activating other cell types in the periphery which then signal to
      primary neurons. Finally, progress in identifying candidate neurotransmitters
      that sensory neurons use to propagate the itch signal is discussed.

PMID- 22466122
TI  - AMPA receptor trafficking in inflammation-induced dorsal horn central
      sensitization.
AB  - Activity-dependent postsynaptic receptor trafficking is critical for long-term
      synaptic plasticity in the brain, but it is unclear whether this mechanism
      actually mediates the spinal cord dorsal horn central sensitization (a specific
      form of synaptic plasticity) that is associated with persistent pain. Recent
      studies have shown that peripheral inflammation drives changes in alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit trafficking
      in the dorsal horn and that such changes contribute to the hypersensitivity that
      underlies persistent pain. Here, we review current evidence to illustrate how
      spinal cord AMPARs participate in the dorsal horn central sensitization
      associated with persistent pain. Understanding these mechanisms may allow the
      development of novel therapeutic strategies for treating persistent pain.

PMID- 22466123
TI  - Interaction and regulatory functions of MU- and delta-opioid receptors in
      nociceptive afferent neurons.
AB  - MU-opioid receptor (MOR) agonists such as morphine are powerful analgesics used
      for pain therapy. However, the use of these drugs is limited by their side
      effects, which include antinociceptive tolerance and dependence. Earlier studies
      reported that MOR analgesic tolerance is reduced by blockade of delta-opioid
      receptors (DORs) that interact with MORs. Recent studies show that the MOR/DOR
      interaction in nociceptive afferent neurons in the dorsal root ganglion may
      contribute to morphine analgesic tolerance. Further analysis of the mechanisms
      for regulating the trafficking of receptors, ion channels and signaling molecules
      in nociceptive afferent neurons would help to understand the nociceptive
      mechanisms and improve pain therapy.

PMID- 22466125
TI  - Oxidative stress induces itch via activation of transient receptor potential
      subtype ankyrin 1 in mice.
AB  - OBJECTIVE: To investigate the role of oxidative stress in itch-indicative
      scratching behavior in mice, and furthermore, to define the cellular and
      molecular mechanisms underlying oxidative stress-mediated itch. METHODS:
      Scratching behavior was induced by intradermal injection of the oxidants hydrogen
      peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in
      mice. The mice were observed for 30 min. RESULTS: Intradermal H2O2 (0.03%-1%) or
      tBHP (1-30 MUmol) elicited robust scratching behavior, displaying an inverted U
      shaped dose-response curve. Naloxone, an opioid receptor antagonist, but not
      morphine, largely suppressed the oxidant-induced scratching. Chlorpheniramine, a
      histamine H1 receptor antagonist, blocked histamine- but not oxidant-induced
      scratching, indicating the involvement of a histamine-independent mechanism in
      oxidant-evoked itch. Further, resiniferatoxin treatment abolished oxidant-induced
      scratching, suggesting an essential role of C-fibers. Notably, blockade of
      transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1
      antagonist HC-030031, or genetic deletion of Trpa1 but not Trpv1 (subfamily V,
      member 1) resulted in a profound reduction in H2O2-evoked scratching. Finally,
      systemic administration of the antioxidant N-acetyl-L-cysteine or trolox (a water
      soluble vitamin E analog) attenuated scratching induced by the oxidants.
      CONCLUSION: Oxidative stress by different oxidants induces profound scratching
      behavior, which is largely histamine- and TRPV1-independent but TRPA1-dependent.
      Antioxidants and TRPA1 antagonists may be used to treat human itch conditions
      associated with oxidative stress.

PMID- 22466126
TI  - Increased function of the TRPV1 channel in small sensory neurons after local
      inflammation or in vitro exposure to the pro-inflammatory cytokine GRO/KC.
AB  - OBJECTIVE: Inflammation at the level of the sensory dorsal root ganglia (DRGs)
      leads to robust mechanical pain behavior and the local inflammation has direct
      excitatory effects on sensory neurons including small, primarily nociceptive,
      neurons. These neurons express the transient receptor potential vanilloid-1
      (TRPV1) channel, which integrates multiple signals of pain and inflammation. The
      aim of this study was to characterize the regulation of the TRPV1 channel by
      local DRG inflammation and by growth-related oncogene (GRO/KC, systemic name:
      CXCL1), a cytokine known to be upregulated in inflamed DRGs. METHODS: Activation
      of the TRPV1 receptor with capsaicin was studied with patch clamp methods in
      acutely isolated small-diameter rat sensory neurons in primary culture. In vivo,
      behavioral effects of TRPV1 and GRO/KC were examined by paw injections. RESULTS:
      Neurons isolated from lumbar DRGs 3 days after local inflammation showed enhanced
      TRPV1 function: tachyphylaxis (the decline in response to repeated applications
      of capsaicin) was significantly reduced. A similar effect on tachyphylaxis was
      observed in neurons pre-treated for 4 h in vitro with GRO/KC. This effect was
      blocked by H-89, a protein kinase A inhibitor. Consistent with the in vitro
      results, in vivo behavioral responses to paw injection of capsaicin were enhanced
      and prolonged by pre-injecting the paw with GRO/KC 4 h before the capsaicin
      injection. GRO/KC paw injections alone did not elicit pain behaviors. CONCLUSION:
      Function of the TRPV1 channel is enhanced by DRG inflammation and these effects
      are preserved in vitro during short-term culture. The effects (decreased
      tachyphylaxis) are mimicked by incubation with GRO/KC, which has previously been
      found to be strongly upregulated in this and other pain models.

PMID- 22466127
TI  - Formaldehyde up-regulates TRPV1 through MAPK and PI3K signaling pathways in a rat
      model of bone cancer pain.
AB  - OBJECTIVE: Our previous study showed that tumor tissue-derived formaldehyde at
      low concentrations plays an important role in bone cancer pain through activating
      transient receptor potential vanilloid subfamily member 1 (TRPV1). The present
      study further explored whether this tumor tissue-derived endogenous formaldehyde
      regulates TRPV1 expression in a rat model of bone cancer pain, and if so, what
      the possible signal pathways are during the development of this type of pain.
      METHODS: A rat model of bone cancer pain was established by injecting living MRMT
      1 tumor cells into the tibia. The formaldehyde levels were determined by high
      performance liquid chromatography, and the expression of TRPV1 was examined with
      Western blot and RT-PCR. In primary cultured dorsal root ganglion (DRG) neurons,
      the expression of TRPV1 was assessed after treatment with 100 umol/L formaldehyde
      with or without pre-addition of PD98059 [an inhibitor for extracellular signal
      regulated kinase], SB203580 (a p38 inhibitor), SP600125 [an inhibitor for c-Jun N
      terminal kinase], BIM [a protein kinase C (PKC) inhibitor] or LY294002 [a
      phosphatidylinositol 3-kinase (PI3K) inhibitor]. RESULTS: In the rat model of
      bone cancer pain, formaldehyde concentration increased in blood plasma, bone
      marrow and the spinal cord. TRPV1 protein expression was also increased in the
      DRG. In primary cultured DRG neurons, 100 MUmol/L formaldehyde significantly
      increased the TRPV1 expression level. Pre-incubation with PD98059, SB203580,
      SP600125 or LY294002, but not BIM, inhibited the formaldehyde-induced increase of
      TRPV1 expression. CONCLUSION: Formaldehyde at a very low concentration up
      regulates TRPV1 expression through mitogen-activated protein kinase and PI3K, but
      not PKC, signaling pathways. These results further support our previous finding
      that TRPV1 in peripheral afferents plays a role in bone cancer pain.

PMID- 22466124
TI  - Emerging role of Toll-like receptors in the control of pain and itch.
AB  - Toll-like receptors (TLRs) are germline-encoded pattern-recognition receptors
      that initiate innate immune responses by recognizing molecular structures shared
      by a wide range of pathogens, known as pathogen-associated molecular patterns
      (PAMPs). After tissue injury or cellular stress, TLRs also detect endogenous
      ligands known as danger-associated molecular patterns (DAMPs). TLRs are expressed
      in both non-neuronal and neuronal cell types in the central nervous system (CNS)
      and contribute to both infectious and non-infectious disorders in the CNS.
      Following tissue insult and nerve injury, TLRs (such as TLR2, TLR3, and TLR4)
      induce the activation of microglia and astrocytes and the production of the
      proinflammatory cytokines in the spinal cord, leading to the development and
      maintenance of inflammatory pain and neuropathic pain. In particular, primary
      sensory neurons, such as nociceptors, express TLRs (e.g., TLR4 and TLR7) to sense
      exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular
      stress. These neuronal TLRs are new players in the processing of pain and itch by
      increasing the excitability of primary sensory neurons. Given the prevalence of
      chronic pain and itch and the suffering of affected people, insights into TLR
      signaling in the nervous system will open a new avenue for the management of
      clinical pain and itch.

PMID- 22466128
TI  - Effects of a non-selective TRPC channel blocker, SKF-96365, on melittin-induced
      spontaneous persistent nociception and inflammatory pain hypersensitivity.
AB  - OBJECTIVE: Melittin is the main peptide in bee venom and causes both persistent
      spontaneous nociception and pain hypersensitivity. Our recent studies indicated
      that both transient receptor potential (TRP) vanilloid receptor 1 (TRPV1) and
      canonical TRPs (TRPCs) are involved in mediating the melittin-induced activation
      of different subpopulations of primary nociceptive cells. Here, we further
      determined whether TRPC channels are involved in melittin-induced inflammatory
      nociceptive responses in behavioral assays. METHODS: The anti-nociceptive and
      anti-hyperalgesic effects of localized peripheral administration of three doses
      of the non-selective TRPC antagonist, SKF-96365 (1-{beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenyl}-1H-imidazole hydrochloride), were
      evaluated in melittin tests. Pain-related behaviors were rated by counting the
      number of paw flinches, and measuring paw withdrawal thermal latency (s) and paw
      withdrawl mechanical threshold (g), over a 1-h time-course. RESULTS: Localized
      peripheral SKF-96365 given before melittin prevented, and given after melittin
      significantly suppressed, the melittin-evoked persistent spontaneous nociception.
      Pre-blockade and post-suppression of activation of primary nociceptive activity
      resulted in decreased hypersensitivity to both thermal and mechanical stimuli
      applied to the primary injury site of the ipsilateral hindpaw, despite dose
      effect differences between thermal and mechanical hyperalgesia. However, local
      administration of SKF-96365 into the contralateral hindpaw had no significant
      effect on any pain-associated behaviors. In addition, SKF-96365 had no effect on
      baseline threshold for either thermal or mechanical sensitivity under normal
      conditions. CONCLUSION: Besides TRPV1, SKF-96365-sensitive TRPC channels might
      also be involved in the pathophysiological processing of melittin-induced
      inflammatory pain and hypersensitivity. Therapeutically, SKF-96365 is equally
      effective in preventing primary thermal and mechanical hyperalgesia as well as
      persistent spontaneous nociception. However, this drug is likely to be more
      effective in the relief of thermal hyperalgesia than mechanical hyperalgesia when
      applied 5 min after establishment of primary afferent activation.

PMID- 22466129
TI  - Disruption of delta-opioid receptor phosphorylation at threonine 161 attenuates
      morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.
AB  - OBJECTIVE: Our previous study identified Threonine 161 (Thr-161), located in the
      second intracellular loop of the delta-opioid receptor (DOR), as the only
      consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of
      this study was to assess the function of DOR phosphorylation by Cdk5 in complete
      Freund's adjuvant (CFA)-induced inflammatory pain and morphine tolerance.
      METHODS: Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory
      pain were acutely dissociated and the biotinylation method was used to explore
      the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and
      paw withdrawal latency was measured after intrathecal delivery of drugs or Tat
      peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory
      pain. RESULTS: Both the total amount and the surface localization of pThr-161-DOR
      were significantly enhanced in the ipsilateral DRG following CFA injection.
      Intrathecal delivery of the engineered Tat fusion-interefering peptide
      corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased
      inflammatory hypersensitivity, and inhibited DOR- but not u-opioid receptor
      mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of
      Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced
      inflammatory pain. CONCLUSION: Phosphorylation of DOR at Thr-161 by Cdk5
      attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA
      induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr
      161 attenuates morphine tolerance.

PMID- 22466131
TI  - Internal medicine interns' and residents' pressure ulcer prevention and
      assessment attitudes and abilities: results of an exploratory study     .
AB  - To evaluate and determine differences between attitudes of internal medicine
      interns and residents toward pressure ulcer (PU) prevention and to evaluate the
      interns' abilities to accurately identify wounds and stage PUs, an exploratory,
      quantitative study was conducted in a 639-bed, safety net academic center.
      Participants (21 internal medicine interns and 21 internal medicine residents)
      attending an educational session on PU prevention and care were eligible to
      participate. The 1-hour conference session was prepared and provided by a
      physician and wound care nurses. Before the lecture, participants were asked to
      complete an 11-question paper-and-pencil PU attitude survey. Following the
      lecture, they were asked to identify 11 wounds and stage PUs using the inpatient
      admission history and physical template used in the hospital's electronic medical
      record. An audience response system was used to record correct and incorrect
      responses. Nineteen (19) interns and 20 residents completed the survey. Twenty
      one (21) interns successfully completed the wound assessment quiz. Descriptive
      statistics were used to examine the survey data and residents' and interns'
      average attitude scores were compared using independent group t-test. The results
      suggest that interns and residents have a positive attitude toward and are
      concerned about PU prevention. The significantly higher overall score among
      interns compared to residents (average 43.8 versus 38.8 respectively, P = 0.002)
      suggests interns have a more positive attitude than residents. Statistically
      significant differences between item scores showed that, compared to residents,
      interns perceived PU prevention to be more time-consuming (P = 0.01), less of a
      concern in practice (P = 0.02), and a lower priority than other areas of care (P
      = 0.003). Compared to residents, interns also were more likely to agree to with
      statement, "In my opinion, patients tend to not get as many pressure ulcers
      nowadays" (P = 0.0006). Both groups agreed that PU prevention is a greater
      priority than treatment and that using risk assessment tools is better than
      relying on clinical judgment. Wound assessment and PU staging results varied
      greatly, ranging from 100% for correct staging of a Stage I PU to 20% correct
      staging of an unstageable PU and 3% correct identification of a diabetic foot
      ulcer. Overall, internal medicine interns and residents have a favorable attitude
      toward PU prevention. Despite the limitations of this study, results suggest that
      enhanced medical school and residency wound care curricula are needed.

PMID- 22466130
TI  - Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in
      descending pain facilitation.
AB  - OBJECTIVE: Despite accumulating evidence on a role of immune cells and their
      associated chemicals in mechanisms of pain, few studies have addressed the
      potential role of chemokines in the descending facilitation of persistent pain.
      The present study was undertaken to test the hypothesis that the chemokine (C-C
      motif) ligand 2 (CCL2) (commonly known as monocyte chemoattractant protein-1)
      signaling in the rostral ventromedial medulla (RVM), a pivotal structure in
      brainstem pain modulatory circuitry, is involved in descending pain facilitation
      in rats. METHODS: An L5 spinal nerve ligation (SNL) was produced in rats under
      pentobarbital anesthesia. Western blot and immunohistochemistry were used to
      detect the expression levels of CCL2 and CCL2 receptor (CCR2), and examine their
      distributions compared with the neuronal marker NeuN as well as glial markers
      glial fibrillary acidic protein (GFAP, astroglial) and CD11b (microglial),
      respectively. RESULTS: SNL induced an increase in CCL2 expression in the RVM, and
      this returned to the control level at 4 weeks after injury. The induced CCL2
      colocalized with NeuN, but not with GFAP and CD11b. CCR2 was also upregulated by
      SNL in the RVM, and this increase lasted for at least 4 weeks. CCR2 was
      colocalized with CD11b but not GFAP. Few RVM neurons also exhibited CCR2
      staining. Neutralizing CCL2 with an anti-CCL2 antibody (0.2-20 ng) or injecting
      RS-102895 (0.1-10 pmol), a CCR2b chemokine receptor antagonist, into the RVM on
      day 1 after SNL, significantly attenuated the established thermal and mechanical
      hypersensitivity. In addition, injection of recombinant rat CCL2 (0.03-3 pmol)
      into the RVM induced dose-dependent hyperalgesia, which was prevented by
      pretreatment with RS-102895 (10 pmol). Interleukin-1beta (IL-1beta), a potent
      inducer of neuronal CCL2, was also selectively upregulated in RVM reactive
      astrocytes. Injection of IL-1beta (120 fmol) into the RVM induced behavioral
      hyperalgesia, which was blocked by RS-102895 (10 pmol). However, an IL-1 receptor
      antagonist (3 pmol) did not prevent CCL2 (3 pmol)-induced hyperalgesia. These
      results suggest that the effect of CCL2 is downstream to IL-1beta signaling.
      CONCLUSION: The IL-1beta and CCL2-CCR2 signaling cascades play a role in neuron
      glia-cytokine interactions and the descending facilitation of neuropathic pain.

PMID- 22466132
TI  - A retrospective, longitudinal study to evaluate healing lower extremity wounds in
      patients with diabetes mellitus and ischemia using standard protocols of care and
      platelet-rich plasma gel in a Japanese wound care program .
AB  - Chronic wounds, especially in patients with diabetes mellitus (DM), are a major
      health challenge in Japan. The goal of wound care centers (WCCs) in Japan is to
      facilitate healing and prevent lower extremity amputations (LEAs) using
      standardized protocols of patient and wound care. The standard treatment
      algorithm includes a complete patient and wound assessment, history, physical
      exam, and a variety of diagnostic tests that determine the need for infection
      control intervention, revascularization, excision and debridement, growth
      factor/platelet rich plasma (PRP) gel therapy, skin graft/ flap, wound
      protection, and education. All patient and wound data are entered in a secure
      central database for all WCCs. To evaluate the outcomes of standard care regimens
      compared to the use of a topical PRP gel treatment in patients with a variety of
      complex wounds, a retrospective, longitudinal study was conducted. Wound outcomes
      from 39 patients with 40 chronic, nonhealing, lower extremity wounds were
      evaluated between two time periods: between first presentation at the WCC (T1)
      and after using standard topical treatments (T2) and between T2 and after using
      the PRP gel treatment (T3). Patient average age was 66.8 years (SD: 10.60) and
      mean wound duration was 99.7 days before treatment (SD: 107.73); and the majority
      of patients (85%) had DM. Wounds were classified as ischemic diabetic (n = 24),
      diabetic (n = 10), ischemic (n = 5), and pressure ulcer (n = 1). DFUs were Wagner
      III (77%) and lV (23%). Of those, 60% were in patients with arteriosclerotic
      obliterans (ASO). Infection (abscess, cellulitis, osteomyelitis, and/or gangrene)
      was present in all wounds and treated using debridement, antibiotic therapy, and
      surgery as deemed appropriate. During the first treatment period (T1 to T2) of
      75.3 days, which included revascularization and/or debridement along with
      standard of care, none of the wounds healed and the average wound area, depth,
      and volume increased. Following topical PRP gel treatment, 83% of wounds healed
      within 145.2 days (T2 to T3) (P = 0.00002). Only one patient required an LEA. The
      results of this study suggest that good healing outcomes and a low amputation
      rate can be obtained with a protocol of supportive care (including
      revascularization procedures) and the PRP gel treatment. Prospective controlled
      studies comparing the use of this PRP gel to other advanced treatments are
      warranted.

PMID- 22466133
TI  - Developing evidence-based algorithms for negative pressure wound therapy in
      adults with acute and chronic wounds: literature and expert-based face validation
      results.
AB  - Negative pressure wound therapy (NPWT) is used extensively in the management of
      acute and chronic wounds, but concerns persist about its efficacy, effectiveness,
      and safety. Available guidelines and algorithms are wound type-specific, not
      evidence-based, and many lack clearly described relative and absolute
      contraindications and stop criteria. The purpose of this research was to: (1)
      develop evidence-based algorithms for the safe use of NPWT in adults with acute
      and chronic wounds by nonwound expert clinicians, and (2) obtain face validity
      for the algorithms. Using NPWT meta-analyses and systematic reviews (n = 10),
      NPWT guidelines of care (n = 12), general evidence-based guidelines of wound care
      (n = 11), and a framework for transitioning between moisture-retentive and NPWT
      care (n = 1), a set of three algorithms was developed. Literature-based validity
      for each of the 39 discreet algorithm steps/decision points was obtained by
      reviewing best available evidence from systematic literature reviews (n = 331
      publications) and abstraction of all NPWT-relevant publications (n = 182) using
      the patient-oriented Strength of Recommendation (SORT) taxonomy. Of the 182 NPWT
      studies abstracted, 25 met criteria for level 1 and 2 evidence but only one
      general assessment step had both level 1 evidence and an "A" strength of
      recommendation. Next, an Institutional Review Board-approved, cross-sectional
      mixed methods survey design face validation pilot study was conducted to solicit
      comments on, and rate the validity of, the 51 discreet algorithm-related
      statements, including the 39 decisions/steps. Twelve (12) of the 15 invited
      interdisciplinary wound experts agreed to participate. The overall algorithm
      content validity index (CVI) was high (0.96 out of 1). Helpful design suggestions
      to ensure safe use were made, and participants suggested an examination of
      commonly used wound definitions in follow-up studies. Results of the literature
      based face validation confirm that the evidence base for using NPWT remains
      limited, especially for chronic wounds, and that safety guidance may be affected
      by the fact that evidence-based ratings cannot accurately reflect relative or
      absolute product contraindications because they simply are not included in
      clinical studies. These findings, the positive expert panel comments, and the
      high CVI confirm the need for an algorithm with explicit NPWT start-and-stop
      criteria and suggest that follow-up content and construct validation of these
      algorithms is warranted.

PMID- 22466134
TI  - Pressure ulcer occurrence following the great East Japan Earthquake: observations
      from a disaster medical assistance team.
AB  - Persons with limited mobility are at risk for pressure ulcers. The development
      of pressure ulcers following earthquakes has been reported secondary to disaster
      related spinal cord injury. In the aftermath of the Great East Japan Earthquake,
      members of a disaster medical assistance team (DMAT), which included plastic
      surgeons and wound, ostomy, and continence (WOC) nurses working in acute care
      hospitals, temporary clinics, evacuation centers, and the community noticed an
      increase in the number of requests for pressure ulcer care. A review of hospital
      records and verbal reports from the community suggested that the incidence of
      Stage III and Stage IV pressure ulcers was 7.7% in an acute care hospital and
      26.4% in home care patients - almost 10 times higher than the normal reported
      incidence in Japan. Patients were mostly elderly and did not have spinal cord
      injuries. Alternating-pressure air mattresses stopped working, alternative
      pressure-redistribution devices could not be delivered, caregivers could not
      reach the homebound, and evacuation centers did not have enough mattresses. It is
      believed that the high percentage of elderly living in the affected areas of
      Japan, combined with limited resources, manpower, and the absence of utilities,
      increased the number of persons with deep pressure ulcers. Following natural
      disasters, DMAT wound care specialists can make important contributions to the
      prevention of these wounds while providing much-needed care to prevent pressure
      ulcer-related complications. Clinician observations suggest that the risk of
      pressure-related injuries following a natural disaster is high, especially among
      the elderly.

PMID- 22466135
TI  - Things we know we know.

PMID- 22466136
TI  - Significant statistics.

PMID- 22466137
TI  - Prescription acetaminophen ingestions associated with hepatic injury and death.
AB  - The U.S. Food and Drug Administration has formally requested that pharmaceutical
      manufacturers limit the amount of acetaminophen (APAP) in prescription products.
      The goal of this study was to describe a state-wide poison control system's
      experience with prescription APAP ingestions that resulted in hepatic injury or
      death. Retrospective analysis of statewide California Poison Control System
      electronic database for cases from the years 2000 through 2009. INCLUSION
      CRITERIA: adults >=18 years of age following therapeutic use of an acetaminophen
      containing prescription with laboratory evidence of liver injury. Forty cases met
      the inclusion criteria. All cases involved at least two concurrent acetaminophen
      containing products. Prescription APAP strengths of 500 mg per tablet or greater
      were involved in 32 of 40 cases (80 %). Thirty patients survived, three died, one
      underwent liver transplantation and seven cases were lost to follow up. The
      ingestion of concentrated prescription APAP-containing medications in combination
      with other sources of APAP can result in severe liver injury and death. Limiting
      the amount of APAP from prescription medications in conjunction with enhanced
      prescriber and patient education regarding the hazards of ingesting multiple APAP
      containing products may assist in decreasing the overall incidence of
      unintentional APAP poisonings in the United States. Future prospective studies
      are required to determine if these measures will have a significant impact on
      both the morbidity and mortality associated with APAP administration.

PMID- 22466138
TI  - Photoion-pair dissociation dynamics of polyatomic molecules with synchrotron
      radiation.
AB  - Positive-negative photoion pairs can be formed in the photoexcitation of
      molecules in the broad energy range from vacuum ultraviolet to soft X-ray.
      Synchrotron radiation is the most suitable photon source and state-of-the-art
      mass spectrometry techniques have been successfully applied in the experimental
      studies of such ion-pair photodissociation dynamics. This perspective will
      briefly review the recent progress on this topic and provide a general
      description of the mechanisms of ion-pair photodissociation dynamics of
      polyatomic molecules. Challenges in the understanding of ion-pair
      photodissociation in the higher photon energy range are also discussed.

PMID- 22466140
TI  - The road to cancer control.

PMID- 22466141
TI  - Design, synthesis and activity study of aminopeptidase N targeted 3-amino-2
      hydroxy-4-phenyl-butanoic acid derivatives.
AB  - A series of (2RS,3S)-3-amino-2-hydroxy-4-phenyl-butanoic acids (AHPA) derivatives
      (MA0-MA7) were synthesized. The in vitro aminopeptidase N (APN) enzyme and cell
      proliferation assay of target compounds were investigated. The results showed
      that most compounds displayed potent inhibitory activities against APN, compound
      MA0 showed even better inhibitory effects than bestatin on both enzyme activity
      and HL60 cell proliferation. The FlexX docking result showed the mode of binding
      between MA0 and APN.

PMID- 22466139
TI  - Immunofluorescent localization of the Rab-GAP protein TBC1D4 (AS160) in mouse
      kidney.
AB  - TBC1D4 (or AS160) was identified as a Rab-GTPase activating protein (Rab-GAP)
      that controls insulin-dependent trafficking of the glucose transporter GLUT4 in
      skeletal muscle cells and in adipocytes. Recent in vitro cell culture studies
      suggest that TBC1D4 may also regulate the intracellular trafficking of kidney
      proteins such as the vasopressin-dependent water channel AQP2, the aldosterone
      regulated epithelial sodium channel ENaC, and the Na(+)-K(+)-ATPase. To study the
      possible role of TBC1D4 in the kidney in vivo, we raised a rabbit polyclonal
      antibody against TBC1D4 to be used for immunoblotting and immunohistochemical
      studies. In immunoblots on mouse kidney homogenates, the antibody recognizes
      specific bands at the expected size of 160 kDa and at lower molecular weights,
      which are absent in kidneys of TBC1D4 deficient mice. Using a variety of nephron
      segment-specific marker proteins, immunohistochemistry reveals TBC1D4 in the
      cytoplasm of the parietal epithelial cells of Bowman's capsule, the thin and
      thick limbs of Henle's loop, the distal convoluted tubule, the connecting tubule,
      and the collecting duct. In the latter, both principal as well as intercalated
      cells are TBC1D4-positive. Thus, with the exception of the proximal tubule,
      TBC1D4 is highly expressed along the nephron and the collecting duct, where it
      may interfere with the intracellular trafficking of many renal transport proteins
      including AQP2, ENaC and Na(+)-K(+)-ATPase. Hence, TBC1D4 may play an important
      role for the control of renal ion and water handling and hence for the control of
      extracellular fluid homeostasis.

PMID- 22466142
TI  - Isolation of mammalian pathogenic bacteria using silkworms.
AB  - We developed a method to predict bacterial pathogenicity against mammals by
      measuring bacterial virulence in silkworms at 37 degrees C, human body
      temperature. One hundred and twenty-two strains of bacteria were isolated from
      the intestines of fish and shellfish and tested for their virulence against
      silkworms. Overnight cultures of 50 strains killed at least 50% of the silkworms
      when injected into the hemolymph. Of 10 strains that showed the most potent
      pathogenicity against silkworms, 8 also killed mice within 4 days after
      injection, including Staphylococcus simiae and Staphylococcus pasteuri, neither
      of which was previously reported to be pathogenic against mammals. These findings
      suggest that bacterial pathogenicity against mammals can be predicted based on
      measurements of silkworm-killing activity.

PMID- 22466143
TI  - Availability of serum corticosterone level for quantitative evaluation of
      morphine withdrawal in mice.
AB  - Physical dependence on morphine is evidenced by the withdrawal syndromes,
      including body weight loss, which are induced by the discontinuation of morphine
      exposure or by the treatment with naloxone, an opioid receptor antagonist. The
      present study was designed to examine whether the elevation of serum
      corticosterone (SCS) level induced by naloxone-precipitated morphine withdrawal
      was a useful index to quantify the physical dependence on morphine in mice, which
      was compared with body weight loss induced by naloxone-precipitated morphine
      withdrawal. The SCS level was dependent on the dosage and the number of dosing of
      morphine and challenging dosage of naloxone. Intraplantar injection of formalin,
      potentially producing inflammatory pain, inhibited both body weight loss and SCS
      increase induced by naloxone challenge in mice receiving repeated exposure of
      morphine, indicating that formalin-induced pain attenuated the development of
      physical dependence on morphine. The magnitude of body weight loss in morphine
      withdrawal was significantly correlated with the magnitude of naloxone challenge
      induced SCS increase. These results suggest that the naloxoneinduced increase in
      SCS level is a quantitative index of the magnitude of physical dependence on
      morphine in mice.

PMID- 22466144
TI  - Therapeutic time window of YGY-E neuroprotection of cerebral ischemic injury in
      rats.
AB  - YGY-E is an active ingredient in traditional Chinese medical herbs which have
      anti-ischemic activity. The present work was designed to study its therapeutic
      time window in cerebral ischemic injury as well as its effect on neuronal
      apoptosis. Animals received an intravenous injection of YGY-E at 1, 3, and 6 h,
      respectively, after permanent focal cerebral ischemia induced by
      electrocoagulation of the middle cerebral artery. Infarct ratio and neurological
      function were employed to assess the effects of YGY-E on the therapeutic time
      window in this animal model. Furthermore, we evaluated effects of this compound
      on neuronal apoptosis and synthesis of Bcl-2 and Bax in ischemic brain tissue
      with in situ DNA end labeling (TUNEL), immunohistochemistry assay, and Western
      blot analysis. YGY-E (2-8 mg/kg) delivered at all the three time points
      dosedependently decreased infarct ratio, neurological deficits, percentage of
      TUNEL-positive cells (p < 0.01) and Bax-positive cells (p < 0.01 or p < 0.05). In
      contrast, it increased the percentage of Bcl-2 positive cells (p < 0.01 or p <
      0.05). These data demonstrated that YGY-E had protective effects against cerebral
      ischemia injuries in rats. But more importantly, they indicate that YGY-E has an
      unusually long (up to 6 h) therapeutic time window relative to classical drugs in
      treating cerebral ischemia. In addition, our results suggest that the anti
      apoptotic effects of YGY-E are due to its regulation of the balance between Bcl-2
      and Bax protein levels.

PMID- 22466145
TI  - Bactericidal action of Alpinia galanga essential oil on food-borne bacteria.
AB  - The use of natural antimicrobial agents is garnering attention due to consumer
      and producer awareness of health problems. This study found that the essential
      oil of A. galanga had strong bactericidal activity against both Gram-negative and
      Gram-positive bacteria. The bactericidal action of A. galanga oil was extremely
      rapid. Results of scanning electron microscopy observations suggested that A.
      galanga oil had antibacterial action probably as a result of its modification of
      the bacterial cell membrane, disrupting the membrane's permeability. This study
      suggested that the essential oil of A. galanga shows promise as a natural
      antimicrobial agent for use as a food preservative.

PMID- 22466146
TI  - Guar gum and hydroxy propyl methylcellulose compressed coated tablets for colonic
      drug delivery: in vitro and in vivo evaluation in healthy human volunteers.
AB  - The objectives of the present study are to evaluate guar gum in combination with
      hydroxyl propyl methylcellulose (HPMC) as compression coat for colonic delivery
      of prednisolone as well as improving the mechanical properties of the compressed
      coated tablets. The core tablets containing 5 mg prednisolone were compression
      coated with 125 mg of coating materials consisted of guar gum alone or mixtures
      of guar gum in combination with different ratios of HPMC. The compressed coated
      tablets were evaluated for their mechanical properties, in vitro drug release and
      in vivo performance in human volunteers. The compressed coated tablets with coats
      containing HPMC exhibited acceptable mechanical properties. In vitro drug release
      studies in pH 7.4 phosphate-buffered saline medium containing 2% (w/v) rat caecal
      content have shown that increase in concentration of HPMC in the prepared coats
      from 10% to 20% resulted in an increase in the release rate. However, further
      increase in HPMC concentration to constitute 30% caused a reduction in the
      release rate. Based on the drug release results, tablets coated with coat
      consisted of 80% guar gum and 20% HPMC were selected for in vivo evaluation. In
      vivo gamma scintigraphic study on human volunteers using technetium-99m
      diethylenetriamine pentaacetic acid as a tracer was performed. The results showed
      that tablets remained intact in stomach and small intestine, however partial and
      complete release of the tracer occurred in the colon. In conclusion, guar gum in
      combination with HPMC would be successfully used as a carrier for drug delivery
      to the colon.

PMID- 22466147
TI  - Development and characterization of local anti-inflammatory implantation for the
      controlled release of the hexane extract of the flower-heads of Euryops
      pectinatus L. (Cass.).
AB  - A hexane extract of the flower-heads of Euryops pectinatus L. (Cass.) was
      formulated into local anti-inflammatory implantation patches with controlled
      release. Cross-linked sodium hyaluronate patches (F1-F3) and chitosan patches (F4
      F6) were prepared by a casting/solvent evaporation technique. Morphological and
      mechanical characterizations including the components ratio, surfactant and the
      loaded amount of the hexane extract (50, 100, and 200 mg/kg b.wt.) were
      investigated. Release studies were performed during 24 h using a diffusion cell.
      Films with optimum in vitro release rate have been investigated for testing the
      anti-inflammatory activity and the sustaining effect of the formulations. The
      sustained anti-inflammatory effect of the hexane extract of E. pectinatus flower
      heads from the selected films was studied by inducing paw edema in rats with 1%
      (w/v) carrageenan solution. The results indicated the compatibility of hexane
      extract with both sodium hyaluronate and chitosan patches forming yellowish
      transparent films. Based on variations in drug release profiles throughout the 24
      h among the formulations (F1-F6) studies, F3 and F6 were selected for further
      investigation. When the films were applied 1 h before the subplantar injection of
      carrageenan in the hind paw of male Albino rats, formulation (F3) provided its
      maximum inhibition of paw edema in rats (91.3%) 4 h after edema induction
      whereas, formulation (F6) showed less inhibition after 4 h (70.6%). The previous
      two formulations (F3 and F6) produced potent results (95.3 and 89.5%,
      respectively) after 24 h when compared with a local market preparation containing
      25% beta-sitosterol used as positive control. Histophathological investigation
      was conducted for 1, 4, and 12 weeks to study the tissue response for the two
      formulations (F3 and F6) at the implantation site. Chemical investigation of the
      hexane extract was achieved for both unsaponifiable matter (USM) and fatty acid
      methyl esters (FAME) using gas liquid chromatography (GLC). The USM was dominated
      by n-pentacosane (14.40%), phytosterols (Cholesterol, Campesterol, Stigmasterol,
      beta-sitosterol, alpha-amyrin) reached 33.44% and the FAME was dominated by
      Linoleinic (49.97%). Quality control of the local implantation was evaluated by
      GLC using cholesterol as an analytical marker and phytosterols as an active
      marker compared to the plain extract.

PMID- 22466148
TI  - A preliminary comparison study of two noncrosslinked biologic meshes used in
      complex ventral hernia repairs.
AB  - BACKGROUND: The biologic materials currently available for hernia repairs are
      costly and there are limited statistics on recurrences and rates of infection in
      connection with their use in complex cases. METHODS: We performed a retrospective
      review and comparison of two types of biologic mesh used at our institution for
      abdominal hernia repairs spanning a 1-year period. Demographic data and outcomes
      relating to surgical site infections, hernia recurrences, and mortality were
      analyzed. Of the 35 patients in the study, 23 patients (Group I) were managed
      with SurgiMend, a neonatal bovine mesh, and 12 patients (Group II) were managed
      with Flex HD, a human-derived mesh. RESULTS: The study cohorts met criteria for
      high-risk stratification based on body mass index, comorbid conditions, and a
      high prevalence of contaminated wounds. The overall surgical site infection rate
      was 17 % for Group I and 50 % for Group II. These differences reached statistical
      significance when comparing superficial infections but not for deep infections
      with mesh involvement. Hernia recurrences in Group I were 5 % compared to 33 % in
      Group II. No deaths were observed. CONCLUSIONS: These preliminary data
      demonstrate promising short-term outcomes for high-risk complex hernias repaired
      with biologic mesh, particularly SurgiMend, but the long-term durability of these
      biological materials is yet to be determined.

PMID- 22466149
TI  - Disc hemorrhage:  is that a risk factor or sign of progression?

PMID- 22466150
TI  - Disc hemorrhage is a sign of progression in normal-tension glaucoma.

PMID- 22466151
TI  - Age-dependent correction factors for goldmann tonometry.

PMID- 22466152
TI  - Corneal mechanical stiffness and its effect on tonometry.

PMID- 22466153
TI  - Effect of erythrocytes on brain water content and haem oxygenase-1 expression in
      rats with traumatic intracerebral haemorrhage.
AB  - BACKGROUND: Studies have demonstrated that brain oedema formation following
      spontaneous intracerebral haemorrhage is associated with substances derived from
      blood clots or blood components. However, these studies did not completely reveal
      the role of blood components in brain oedema formation following traumatic
      intracerebral haemorrhage (TICH). Here, we explore the role of erythrocytes in
      brain oedema development by studying the effect of erythrocytes on brain water
      content (BWC) and expression of haem oxygenase-1 (HO-1) in rats with TICH.
      METHODS: A total of 120 Sprague-Dawley rats were randomly divided into four
      experimental treatment groups: traumatic brain injury (TBI), TBI plus whole blood
      (WB), TBI plus lysed red blood cells (RBCs; LRBC) and TBI plus packed RBCs
      (PRBC). Following TBI, which was established by applying a free-falling device,
      WB, LRBC or PRBC were infused with stereotactic guidance into the injured cortex
      to produce a model of TICH. All rats were killed at 1, 3 or 5 days after TBI or
      TICH. BWC was measured, and immunohistochemistry for HO-1 was performed. RESULTS:
      In the WB, PRBC and TBI groups, BWC at 3 days post-TBI or post-TICH was the
      greatest. However, BWC in the LRBC group at 1 day was markedly higher than that
      at 3 and 5 days. Comparisons among the four groups showed that BWC in the LRBC
      group was the highest at 1 day, and the highest at 3 days in the WB and PRBC
      groups; there was no significant difference at 5 days. Positive expression of HO
      1 in the WB, PRBC and LRBC groups coincided with changes in BWC. CONCLUSIONS: Our
      results indicate that erythrocytes play an important role in delayed brain oedema
      formation (3 days post-injury) following TICH, but have no significant influence
      on brain oedema at early stages (1 day post-injury), and that the mechanisms of
      delayed brain oedema involve RBC breakdown products.

PMID- 22466154
TI  - Supratentorial and infratentorial brain abscess.

PMID- 22466155
TI  - Intragenomic spread of plastid-targeting presequences in the coccolithophore
      Emiliania huxleyi.
AB  - Nucleus-encoded plastid-targeted proteins of photosynthetic organisms are
      generally equipped with an N-terminal presequence required for crossing the
      plastid membranes. The acquisition of these presequences played a fundamental
      role in the establishment of plastids. Here, we report a unique case of two non
      homologous proteins possessing completely identical presequences consisting of a
      bipartite plastid-targeting signal in the coccolithophore Emiliania huxleyi. We
      further show that this presequence is highly conserved in five additional
      proteins that did not originally function in plastids, representing de novo
      plastid acquisitions. These are among the most recent cases of presequence
      spreading from gene to gene and shed light on important evolutionary processes
      that have been usually erased by the ancient history of plastid evolution. We
      propose a mechanism of acquisition involving genomic duplications and gene
      replacement through non-homologous recombination that may have played a more
      general role for equipping proteins with targeting information.

PMID- 22466156
TI  - Changing trends in incidence and aetiology of childhood acute non-traumatic coma
      over a period of changing malaria transmission in rural coastal Kenya: a
      retrospective analysis.
AB  - OBJECTIVES: Recent changes in malaria transmission have likely altered the
      aetiology and outcome of childhood coma in sub-Saharan Africa. The authors
      conducted this study to examine change in incidence, aetiology, clinical
      presentation, mortality and risk factors for death in childhood non-traumatic
      coma over a 6-year period. DESIGN: Retrospective analysis of prospectively
      collected data. SETTING: Secondary level health facility: Kilifi, Coast, Kenya.
      PARTICIPANTS: Children aged 9 months to 13 years admitted with acute non
      traumatic coma (Blantyre Coma Score =2) between January 2004 and December 2009 to
      Kilifi District Hospital, Kenya. EXCLUSION CRITERIA: delayed development,
      epilepsy and sickle cell disease. RESULTS: During the study period, 665 children
      (median age 32 (IQR 20-46) months; 46% were girls) were admitted in coma. The
      incidence of childhood coma declined from 93/100 000 children in 2004 to 44/100
      000 children in 2009. There was a 64% overall drop in annual malaria-positive
      coma admissions and a 272% overall increase in annual admissions with
      encephalopathies of undetermined cause over the study period. There was no change
      in case death of coma. Vomiting, breathing difficulties, bradycardia, profound
      coma (Blantyre Coma Score=0), bacteraemia and clinical signs of meningitis were
      associated with increased risk of death. Seizures within 24 h prior to admission,
      and malaria parasitaemia, were independently associated with survival, unchanging
      during the study period. CONCLUSION: The decline in the incidence and number of
      admissions of childhood acute non-traumatic coma is due to decreased malaria
      transmission. The relative and absolute increase in admissions of encephalopathy
      of undetermined aetiology could represent aetiologies previously masked by
      malaria or new aetiologies.

PMID- 22466157
TI  - Does antiretroviral therapy initiation increase sexual risk taking in Kenyan
      female sex workers? A retrospective case-control study.
AB  - OBJECTIVES: Although antiretroviral therapy (ART) prolongs life and reduces
      infectiousness, in some contexts, it has been associated with increased sexual
      risk taking. DESIGN: Retrospective case-control study. SETTING: Nairobi-based
      dedicated female sex worker (FSW) clinic. PARTICIPANTS: HIV-infected FSWs before
      and after ART initiation (n=62); HIV-infected and -uninfected control FSWs not
      starting ART during the same follow-up period (n=40). INTERVENTION: Initiation of
      ART. PRIMARY OUTCOME MEASURES: Self-reported condom use, client numbers and
      sexually transmitted infection incidence over the study period (before and after
      ART initiation in cases). RESULTS: Sexual risk-taking behaviour with casual
      clients did not increase after ART initiation; condom use increased and sexually
      transmitted infection incidence decreased in both cases and controls, likely due
      to successful cohort-wide HIV prevention efforts. CONCLUSIONS: ART provision was
      not associated with increases in unsafe sex in this FSW population.

PMID- 22466158
TI  - ANRS-COM'TEST: description of a community-based HIV testing intervention in non
      medical settings for men who have sex with men.
AB  - OBJECTIVE: To describe a community-based HIV testing programme. DESIGN AND
      SETTING: An intervention of HIV voluntary testing conducted in non-medical
      settings in four French cities. PARTICIPANTS: Men who have sex with men (MSM).
      INTERVENTION: Counselling and rapid HIV testing staffed by trained personnel from
      an HIV/AIDS community-based organisation. PRIMARY AND SECONDARY OUTCOME MEASURES:
      The population that has taken hold of the intervention and the satisfaction of
      participants. Data were collected on demographics, HIV testing history, sexual
      practices and satisfaction with the testing programme. RESULTS: 532 MSM were
      tested between February 2009 and June 2010, of whom 49 (9%) were tested two or
      more times. 468 MSM (88%) had casual male partners in the previous 6 months, and
      152 (35%) reported having unprotected anal intercourse with risky casual partners
      (HIV infected or HIV serostatus unknown). 159 men (30%) had not been tested in
      the previous 2 years, and 50 (31%) of whom had unprotected anal intercourse with
      risky casual partners. Among the 15 patients who tested positive (2.8%), 12 (80%)
      received confirmation and were linked to care (median CD4 cell count =550/mm(3)).
      Satisfaction was high: 92% reported being 'very satisfied' with their experience.
      Steps of counselling and testing procedure were respected by testers and
      difficulties in handling tests were rare. CONCLUSIONS: This community-based HIV
      testing programme reached high-risk MSM, of whom a substantial proportion had not
      been tested lately. This novel service supplements pre-existing HIV testing
      services and increases access to HIV testing in high-risk groups.

PMID- 22466159
TI  - The association between childhood cognitive ability and adult long-term sickness
      absence in three British birth cohorts: a cohort study.
AB  - OBJECTIVES: The authors aimed to test the relationship between childhood
      cognitive function and long-term sick leave in adult life and whether any
      relationship was mediated by educational attainment, adult social class or adult
      mental ill-health. DESIGN: Cohort study. SETTING: The authors used data from the
      1946, 1958 and 1970 British birth cohorts. Initial study populations included all
      live births in 1 week in that year. Follow-up arrangements have differed between
      the cohorts. PARTICIPANTS: The authors included only those alive, living in the
      UK and not permanent refusals at the time of the outcome. The authors further
      restricted analyses to those in employment, full-time education or caring for a
      family in the sweep immediately prior to the outcome. 2894 (1946), 15 053 (1958)
      and 14 713 (1970) cohort members were included. PRIMARY AND SECONDARY OUTCOME
      MEASURES: receipt of health-related benefits (eg, incapacity benefit) in 2000 and
      2004 for the 1958 and 1970 cohorts, respectively, and individuals identified as
      'permanently sick or disabled' in 1999 for 1946 cohort. RESULTS: After adjusting
      for sex and parental social class, better cognitive function at age 10/11 was
      associated with reduced odds of being long-term sick (1946: 0.70 (0.56 to 0.86),
      p=0.001; 1958: 0.69 (0.61 to 0.77), p<0.001; 1970: 0.80 (0.66 to 0.97), p=0.003).
      Educational attainment appeared to partly mediate the associations in all
      cohorts; adult social class appeared to have a mediating role in the 1946 cohort.
      CONCLUSIONS: Long-term sick leave is a complex outcome with many risk factors
      beyond health. Cognitive abilities might impact on the way individuals are able
      to develop strategies to maintain their employment or rapidly find new employment
      when faced with a range of difficulties. Education should form part of the policy
      response to long-term sick leave such that young people are better equipped with
      skills needed in a flexible labour market.

PMID- 22466160
TI  - Oxidation of retinoic acids in hepatic microsomes of wild bullfrogs Lithobates
      catesbeianus environmentally-exposed to a gradient of agricultural contamination.
AB  - Agricultural contaminants are suspected of contributing to the increased
      incidence of deformities and the decline of amphibians populations worldwide.
      Many authors have further suggested that a retinoid effect could be implicated in
      teratogenic mechanisms since the reported deformities resemble those caused by
      abnormal levels of retinoic acid (RA). We previously reported altered retinoid
      concentrations in male bullfrogs from the Yamaska River basin (Quebec, Canada)
      associated with moderate-to-high agricultural activity, and the findings were
      consistent with a possible effect on hepatic RA oxidation. An in vitro assay was
      therefore optimized and hepatic microsomal RA oxidation in bullfrogs was found to
      be quite different from that of other vertebrates. With either all-transRA (atRA)
      or 13cisRA as the substrate, the major metabolite generated was at4-oxo-RA. The
      reaction with 13cisRA as substrate, markedly greater compared with atRA, was
      enhanced in the presence of a reducing agent and inhibited by cytochrome P450
      inhibitors in a dose-dependent manner. Hepatic RA oxidation in male bullfrogs
      showed significant differences between sites with no clear relationship to a
      gradient of agricultural activity or 13cis-4-oxo-RA quantified in plasma. In
      contrast, the in vitro RA oxidation in females increased with the levels of
      contamination and coincided in vivo with higher plasma 13cis-4-oxo-RA
      concentration. The levels of circulating 4-oxo-derivatives could be influenced by
      hepatic RA oxidative metabolism as well as isomerization conditions or RA
      precursor levels.

PMID- 22466161
TI  - Caveolae-mediated endocytosis of biocompatible gold nanoparticles in living Hela
      cells.
AB  - Efficient intracellular delivery of gold nanoparticles (AuNPs) and unraveling the
      mechanism underlying the intracellular delivery are essential for advancing the
      applications of AuNPs toward in vivo imaging and therapeutic interventions. We
      employed fluorescence microscopy to investigate the internalization mechanism of
      small-size AuNPs by living Hela cells. Herein, we found that the caveolae
      mediated endocytosis was the dominant pathway for the intracellular delivery of
      small-size AuNPs. The intracellular delivery was suppressed when we depleted the
      cholesterol with methyl-beta-cyclodextrin (MbetaCD); in contrast, the sucrose
      that disrupts the formation of clathrin-mediated endocytosis did not block the
      endocytosis of AuNPs. Meanwhile, we examined the intracellular localization of
      AuNPs in endocytic vesicles by fluorescent colocalization. This work would
      provide a potential technique to study the intracellular delivery of small-size
      nanoparticles for biomedical applications.

PMID- 22466162
TI  - Characterization of 40 kDa poly(ethylene glycol) polymers by proton transfer
      reaction QTOF mass spectrometry and 1H-NMR spectroscopy.
AB  - Several electrospray mass spectrometry (ESI-MS) techniques have been described
      during the past years to enable the characterization work of large poly(ethylene
      glycol)s (PEGs) and PEGylated proteins. The proton transfer reaction ESI-MS
      method utilizes amines to charge reduce the electrospray envelope of PEGs, hence
      PEG molecules are aminated instead of protonated. This method simplifies the mass
      spectrum of large PEGs, and enables the interpretation of the charge state of the
      observable envelopes (R >= 3,000 (FWHM) measured at the (M + 6H)(6+) ion from 40
      K PEG compound 7,324.19). Hence, deconvolution of the MS data can be performed
      and relative molecular masses of the individual chain lengths of the PEGs can be
      calculated. However, as the poly-dispersity of PEGs may vary from batch to batch
      and from sample to sample, it was of interest to examine if the method could
      distinguish between these kinds of different material. Therefore, sample
      materials of each intermediate obtained at five synthetic steps during synthesis
      of a 40 kDa PEG molecule were collected. These four intermediates, starting
      material and the target molecule were examined by (1)H-NMR spectroscopy and ESI
      MS using a proton stripping base. The study revealed that the charge-stripping
      ESI-MS method is able to differentiate between even small changes in the
      structure of the polymeric molecules only when the analysis is assisted by (1)H
      NMR spectroscopy. A proper characterization of polymer molecules requires besides
      relative molecular mass, also poly-dispersity and end-group characterization. No
      end-group information is obtained based on MS data. Examination of the PEG
      polymers by (1)H-NMR spectroscopy provides the needed information. In addition,
      the (1)H-NMR spectra clearly distinguishes the examined polymers.

PMID- 22466163
TI  - Amount of CD4+CD25+ regulatory T cells in autoimmune pancreatitis and pilonidal
      sinus.
AB  - OBJECTIVES: Infiltration of many IgG4-positive plasma cells (G4-Ps) is seen in
      IgG4-related diseases and in several "non-IgG4-related diseases," such as
      pilonidal sinus (PS) as well. The involvement of CD4+CD25+ regulatory T cells
      (CD4CD25 Tregs) in IgG4-related diseases has been reported. To see whether
      CD4+CD25+ Tregs are involved in autoimmune pancreatitis (AIP)/non-IgG4-related
      diseases with many G4-Ps, we investigated the amount of G4-Ps and CD4+CD25+ Tregs
      histologically in AIP/PS. METHODS: Four AIP and 10 PS were immunostained with
      IgG4/Foxp3, a specific marker for CD4+CD25+ Tregs. Double immunohistochemistry
      and dual fluorescent immunohistochemistry were conducted to see the amount of
      CD4+CD25+ Tregs. RESULTS: All AIP and 30% of PS showed abundant G4-Ps. G4-Ps
      infiltrated diffusely for all AIPs and in a patchy pattern for PS at the
      abscess/granulation foci. Foxp3 immunostaining/double immunohistochemistry showed
      moderate to abundant CD4+CD25+ Tregs in AIP and abscess of PS, but few to
      moderate in granulation of PS. Dual fluorescent immunohistochemistry also showed
      many CD4+CD25+ Tregs in AIP. CONCLUSIONS: Many CD4+CD25+ Tregs were seen in AIP
      lesions, abscess of PS, but not in granulation of PS, suggesting that the amount
      of CD4+CD25+ Tregs sometimes do not synchronize with that of G4-Ps and might
      relate to the inflammatory activity of both AIP and PS.

PMID- 22466164
TI  - Associations of ATP-binding cassette transporter A1 and G1 with insulin secretion
      in human insulinomas.
AB  - OBJECTIVES: Adenosine triphosphate-binding cassette transporter A1 (ABCA1) and G1
      (ABCG1) are 2 important cholesterol transporters in human pancreatic beta-cells.
      The aim of this study was to investigate their alteration in insulinomas and
      their potential associations with abnormal insulin secretion in these patients.
      METHODS: Six patients with insulinoma and 6 healthy controls were recruited.
      Lipid profiles and glucose metabolism were measured. Insulin content, ABCA1, and
      ABCG1 in insulinomas and the adjacent islets of the 6 patients with insulinoma
      were detected by immunohistochemistry or immunofluorescence. RESULTS: Plasma
      total cholesterol, high-density lipoprotein, low-density lipoprotein, and
      triglyceride were comparable between the controls and the patients with
      insulinoma. Fasting glucose was less than 2.8 mmol/L, and insulin release index
      was greater than 0.3 in each patient. Serum insulin fell extremely, and blood
      glucose reached the reference range within an hour after the cutting of the
      tumors in 2 patients with insulinoma. Adenosine triphosphate-binding cassette
      transporter G1 increased in insulinomas compared with the adjacent islets.
      However, ABCA1 was detected neither in the adjacent islets nor in insulinomas.
      Adenosine triphosphate-binding cassette transporter G1 expression in insulinomas
      was significantly associated with fasting insulin level and insulin release
      index. CONCLUSIONS: Increased ABCG1 may contribute to insulin hypersecretion in
      insulinomas. In contrast, the undetectable ABCA1 in insulinomas may reflect a
      negative feedback in insulin secretion in these patients.

PMID- 22466165
TI  - Combined effects of chronic and acute ethanol on pancreatic injury and
      microcirculation.
AB  - OBJECTIVES: Aim of the study was to investigate pancreatic microcirculatory and
      histopathological changes in rats after chronic ethanol liquid diet feeding.
      METHODS: To investigate the influence of chronic alcohol exposition (CAE) on the
      pancreas, rats were fed with either Lieber-DeCarli (LDC) control diet or LDC
      alcohol diet for 2, 4, or 6 weeks and received additionally an acute ethanol
      administration (AEA) for 90 minutes. Intravital microscopy was performed at
      baseline, 45 minutes, and 90 minutes after starting AEA. Pancreatic perfusion and
      leukocyte adhesion were assessed, and pancreatic damage was evaluated by
      histology. RESULTS: Capillary perfusion was reduced in all animals after AEA.
      After previous CAE, there was a significant increase in leukocyte adhesion
      compared to control groups (P < 0.05). Most importantly, leukocyte adhesions were
      already increased at baseline after CAE and before the acute bolus was infused (P
      < 0.05). Moreover, only animals that received LDC alcohol diet developed mild
      histological changes consisting of pancreatic edema and vacuoles, whereas those
      that received AEA alone did not. Histological changes and cytokine levels
      correlated with the duration of prior CAE. CONCLUSIONS: Long-term alcohol intake
      activates endothelium and sensitizes the pancreas for inflammatory reactions
      leading to an increased likelihood of a clinically evident episode of acute
      pancreatitis.

PMID- 22466166
TI  - MicroRNA expression aids the preoperative diagnosis of pancreatic ductal
      adenocarcinoma.
AB  - OBJECTIVES: This study aimed to evaluate microRNA (miRNA) expression in
      pancreatic resection specimens and fine needle aspiration biopsies and determine
      which, if any, miRNAs aid the distinction between benign and malignant pancreatic
      tumors in limited cytology material. METHODS: Resection specimens containing
      adenocarcinoma (n = 17), intraductal papillary mucinous neoplasms (n = 11), and
      nonneoplastic tissues (n = 15) were evaluated for miR-21, miR-221, miR-100, miR
      155, and miR-181b expression by quantitative reverse transcriptase polymerase
      chain reaction (qRT-PCR), and a subset of carcinomas and intraductal papillary
      mucinous neoplasms was analyzed with miRNA microarrays. Cellblocks containing
      carcinoma (n = 26) or benign pancreatic lesions (n = 11) from fine needle
      aspiration biopsies were subjected to qRT-PCR for miR-21, miR-221, miR-181b, miR
      196a, and miR-217. RESULTS: Carcinomas showed higher expression of miR-21, miR
      221, miR-155, miR-100, and miR-181b than benign lesions by qRT-PCR, and
      overexpression of miR-21, miR-221, and miR-181b was confirmed by microarray
      analysis. Cellblocks containing carcinoma showed higher expression of miR-21, miR
      221, and miR-196a than those from benign lesions (P < 0.001, P = 0.009, and P <
      0.001, respectively). CONCLUSIONS: Pancreatic ductal adenocarcinomas show
      differential expression of miRNAs compared to benign pancreatic lesions. A select
      panel of miRNAs aids the distinction between pancreatic lesions in cytology
      specimens.

PMID- 22466167
TI  - Nationwide epidemiological survey of autoimmune pancreatitis in Japan.
AB  - OBJECTIVES: To clarify the clinicoepidemiological features of autoimmune
      pancreatitis (AIP) in Japan, the nationwide survey was conducted. METHODS:
      Patients with AIP who had visited the selected hospitals in 2007 were surveyed.
      Autoimmune pancreatitis was diagnosed according to the Japanese clinical
      diagnostic criteria 2006. The study consisted of 2-stage surveys: the number of
      patients with AIP was estimated by the first questionnaire and their clinical
      features were assessed by the second questionnaire. RESULTS: The estimated total
      number of AIP patients in 2007 was 2790 (95% confidence interval, 2540-3040),
      with an overall prevalence rate of 2.2 per 100,000 populations. The number of
      patients, who were newly diagnosed as AIP, was estimated to be 1120 (95%
      confidence interval, 1000-1240), with an annual incidence rate of 0.9 per 100,000
      populations. Sex ratio (male to female) was 3.7, and the mean (SD) age was 63.0
      (11.4) years. Among the 546 patients whose clinical information was obtained,
      87.6% of the patients presented high serum immunoglobulin G4 levels (>= 135
      mg/dL), and 83% received steroid therapy. CONCLUSIONS: The data represent the
      current clinical features of AIP in Japan. From the results, most AIP patients in
      Japan can be categorized to type 1 AIP according to the recent classification of
      AIP.

PMID- 22466168
TI  - Risk of venous thromboembolism in oral contraceptive users varies according to
      progestin type.

PMID- 22466169
TI  - Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between
      mRNA synthesis and degradation.
AB  - To monitor eukaryotic mRNA metabolism, we developed comparative dynamic
      transcriptome analysis (cDTA). cDTA provides absolute rates of mRNA synthesis and
      decay in Saccharomyces cerevisiae (Sc) cells with the use of Schizosaccharomyces
      pombe (Sp) as an internal standard. cDTA uses nonperturbing metabolic labeling
      that supersedes conventional methods for mRNA turnover analysis. cDTA reveals
      that Sc and Sp transcripts that encode orthologous proteins have similar
      synthesis rates, whereas decay rates are fivefold lower in Sp, resulting in
      similar mRNA concentrations despite the larger Sp cell volume. cDTA of Sc mutants
      reveals that a eukaryote can buffer mRNA levels. Impairing transcription with a
      point mutation in RNA polymerase (Pol) II causes decreased mRNA synthesis rates
      as expected, but also decreased decay rates. Impairing mRNA degradation by
      deleting deadenylase subunits of the Ccr4-Not complex causes decreased decay
      rates as expected, but also decreased synthesis rates. Extended kinetic modeling
      reveals mutual feedback between mRNA synthesis and degradation that may be
      achieved by a factor that inhibits synthesis and enhances degradation.

PMID- 22466171
TI  - Bisulfite sequencing of chromatin immunoprecipitated DNA (BisChIP-seq) directly
      informs methylation status of histone-modified DNA.
AB  - The complex relationship between DNA methylation, chromatin modification, and
      underlying DNA sequence is often difficult to unravel with existing technologies.
      Here, we describe a novel technique based on high-throughput sequencing of
      bisulfite-treated chromatin immunoprecipitated DNA (BisChIP-seq), which can
      directly interrogate genetic and epigenetic processes that occur in normal and
      diseased cells. Unlike most previous reports based on correlative techniques, we
      found using direct bisulfite sequencing of Polycomb H3K27me3-enriched DNA from
      normal and prostate cancer cells that DNA methylation and H3K27me3-marked
      histones are not always mutually exclusive, but can co-occur in a genomic region
      dependent manner. Notably, in cancer, the co-dependency of marks is largely
      redistributed with an increase of the dual repressive marks at CpG islands and
      transcription start sites of silent genes. In contrast, there is a loss of DNA
      methylation in intergenic H3K27me3-marked regions. Allele-specific methylation
      status derived from the BisChIP-seq data clearly showed that both methylated and
      unmethylated alleles can simultaneously be associated with H3K27me3 histones,
      highlighting that DNA methylation status in these regions is not dependent on
      Polycomb chromatin status. BisChIP-seq is a novel approach that can be widely
      applied to directly interrogate the genomic relationship between allele-specific
      DNA methylation, histone modification, or other important epigenetic regulators.

PMID- 22466170
TI  - Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of
      chromatin and DNA methylation cross-talk.
AB  - Cross-talk between DNA methylation and histone modifications drives the
      establishment of composite epigenetic signatures and is traditionally studied
      using correlative rather than direct approaches. Here, we present sequential ChIP
      bisulfite-sequencing (ChIP-BS-seq) as an approach to quantitatively assess DNA
      methylation patterns associated with chromatin modifications or chromatin
      associated factors directly. A chromatin-immunoprecipitation (ChIP)-capturing
      step is used to obtain a restricted representation of the genome occupied by the
      epigenetic feature of interest, for which a single-base resolution DNA
      methylation map is then generated. When applied to H3 lysine 27 trimethylation
      (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout
      most of the genome, except for CpG islands, where these two marks are mutually
      exclusive. Further ChIP-BS-seq-based analysis in Dnmt triple-knockout (TKO)
      embryonic stem cells revealed that total loss of CpG methylation is associated
      with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized
      peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed.
      At an even broader scale, these BLOCs correspond to regions of high DNA
      methylation in wild-type ES cells, suggesting that DNA methylation prevents
      H3K27me3 deposition locally and at a megabase scale. Our strategy provides a
      unique way of investigating global interdependencies between DNA methylation and
      other chromatin features.

PMID- 22466173
TI  - Fourier magnitude of the field incident on a random scattering medium from
      spatial speckle intensity correlations.
AB  - Spatial speckle intensity correlations are used to determine the spatial Fourier
      magnitude of a field incident on a random scattering medium. The patterned beam
      is scanned across the scattering medium, and the speckle pattern on the opposite
      side is imaged at each beam position. A theory based on a Green's function
      representation is used to reconstruct the spatial Fourier magnitude of the
      patterned incident field.

PMID- 22466172
TI  - Ultra-low-input, tagmentation-based whole-genome bisulfite sequencing.
AB  - We have adapted transposase-based in vitro shotgun library construction
      ("tagmentation") for whole-genome bisulfite sequencing. This method, Tn5mC-seq,
      enables a >100-fold reduction in starting material relative to conventional
      protocols, such that we generate highly complex bisulfite sequencing libraries
      from as little as 10 ng of input DNA, and ample useful sequences from 1 ng of
      input DNA. We demonstrate Tn5mC-seq by sequencing the methylome of a human
      lymphoblastoid cell line to ~8.6* high-quality coverage of each strand.

PMID- 22466174
TI  - High-speed addition/subtraction/complement/doubling of quaternary numbers using
      optical nonlinearities and DQPSK signals.
AB  - We propose an innovative approach to implementing multiple arithmetic functions
      of quaternary numbers using optical nonlinearities and differential quadrature
      phase-shift keying (DQPSK) signals. By adopting 100 Gbit/s DQPSK signals (A, B)
      and exploiting nondegenerate four-wave mixing (FWM) for addition/subtraction and
      degenerate FWM for complement and doubling in a single highly nonlinear fiber, we
      demonstrate 50 Gbaud/s simultaneous quaternary addition (A+B), dual-directional
      subtraction (A-B, B-A), complement (-A, -B), and doubling (2B). Power penalties
      less than 4 dB (addition), 3 dB (dual-directional subtraction), 2 dB
      (complement), and 3.1 dB (doubling) are observed at a bit-error rate of 10(-9).

PMID- 22466175
TI  - Digital holographic microscopy characterization of superdirective beam by
      metamaterial.
AB  - Digital holographic microscopy (DHM) has been successfully applied for the first
      time to characterize the radiative out-of-plane emission properties of a
      superdirective device. Complementarily to near-field microscopy, DHM allows us to
      reconstruct the beam in the far-field region. The angular dispersion of the light
      beam radiated from a grating composed of air and anti-air metamaterial has been
      determined, and the proposed technique has highlighted a collimation degree
      higher than 0.04 degrees , as already evaluated in a previous work. Further
      considerations on the retrieved phase map of the beam in the acquisition plane
      are presented.

PMID- 22466176
TI  - Synthesis of fractal light pulses by quasi-direct space-to-time pulse shaping.
AB  - We demonstrated a simple diffractive method to map the self-similar structure
      shown in squared radial coordinate of any set of circularly symmetric fractal
      plates into self-similar light pulses in the corresponding temporal domain. The
      space-to-time mapping of the plates was carried out by means of a kinoform
      diffractive lens under femtosecond illumination. The spatio-temporal
      characteristics of the fractal pulses obtained in this way were measured by means
      of a spectral interferometry technique assisted by a fiber optics coupler
      (STARFISH). Our proposal allows synthesizing suited sequences of focused fractal
      femtosecond pulses potentially useful for several current applications, such as
      femtosecond material processing, atomic, and molecular control of chemical
      processes or generation of nonlinear effects.

PMID- 22466177
TI  - Single-pass waveguide amplifiers in Er-Yb doped zinc polyphosphate glass
      fabricated with femtosecond laser pulses.
AB  - We have investigated the direct fabrication of subsurface waveguide amplifiers in
      Er-Yb zinc polyphosphate glass by utilizing the relationship between the initial
      glass composition and the resulting changes to the network structure after
      modification by fs laser pulses. Waveguides, exhibiting internal gain of 1 dB/cm
      at 1.53 MUm when pumped with 500 mW at 976 nm, were directly fabricated using a
      regenerative amplified Ti:sapphire 1 kHz, 180 fs laser system. Optical properties
      as well as insertion losses and internal gain are reported.

PMID- 22466178
TI  - Efficient, resonantly pumped, room-temperature Er3+:GdVO4 laser.
AB  - We report an efficient room-temperature operation of a resonantly pumped
      Er3+:GdVO4 laser at 1598.5 nm. The maximum continuous wave (CW) output power of
      3.5 W with slope efficiency of 56% was achieved with resonant pumping by an Er
      fiber laser at 1538.6 nm. With pumping by a commercial laser diode bar stack, a
      quasi-CW (QCW) output of 7.7 W and maximum slope efficiency of ~53% versus
      absorbed pump power were obtained. This is believed to be the first resonantly
      (in-band) pumped, room-temperature Er3+:GdVO4 laser.

PMID- 22466179
TI  - Reconfigurable wavefront sensor for ultrashort pulses.
AB  - A highly flexible Shack-Hartmann wavefront sensor for ultrashort pulse
      diagnostics is presented. The temporal system performance is studied in detail.
      Reflective operation is enabled by programming tilt-tolerant microaxicons into a
      liquid-crystal-on-silicon spatial light modulator. Nearly undistorted pulse
      transfer is obtained by generating nondiffracting needle beams as subbeams.
      Reproducible wavefront analysis and spatially resolved second-order
      autocorrelation are demonstrated at incident angles up to 50 degrees  and pulse
      durations down to 6 fs.

PMID- 22466180
TI  - Relative intensity noise and frequency noise of a compact Brillouin laser made of
      As38Se62 suspended-core chalcogenide fiber.
AB  - Relative intensity noise and frequency noise have been measured for the first
      time for a single-frequency Brillouin chalcogenide As38Se62 fiber laser. This is
      also the first demonstration of a compact suspended-core fiber Brillouin laser,
      which exhibits a low threshold power of 22 mW and a slope efficiency of 26% for
      nonresonant pumping.

PMID- 22466181
TI  - Diode-pumped continuous-wave eye-safe Nd:YAG laser at 1415 nm.
AB  - We describe the output performance of the 1415 nm emission in Nd:YAG in a plane
      concave cavity under traditional pumping into the 4F5/2 level (808 nm) and direct
      in-band pumping into the 4F3/2 level (885 nm). An end-pumped Nd:YAG laser yielded
      maximum cw output power of 6.3 W and 4.2 W at 885 nm and 808 nm laser diode (LD)
      pumping, respectively. To the best of our knowledge, this is the highest output
      power of a LD-pumped 1415 nm laser.

PMID- 22466182
TI  - High-efficiency 1.9 um Tm3+:LiLuF4 thin-disk laser.
AB  - We present the first demonstration of a 792 nm diode-pumped Tm3+:LiLuF4 thin-disk
      laser operation around 1.9 MUm. In multimode configuration, up to 21 W of output
      power and a maximal slope efficiency of 49% with an optical-to-optical efficiency
      of 40% was demonstrated. A tuning range from 1899 nm to 1927 nm could be achieved
      by inserting an etalon into the cavity.

PMID- 22466183
TI  - Temperature dependence and quantum efficiency of ultrabroad NIR photoluminescence
      from Ni2+ centers in nanocrystalline Ba-Al titanate glass ceramics.
AB  - Ultrabroad near-infrared (NIR) photoluminescence from Ni2+-centers in
      nanocrystalline Ba-Al titanate glass ceramics was studied by temperature
      dependent static and dynamic photoluminescence spectroscopy in the regime of 10
      to 300 K. Photoluminescence covers the spectral range of about 1100 nm to >1600
      nm with a typical bandwidth (FWHM) greater than 300 nm. For UV-LED excitation at
      352 nm, an internal quantum efficiency of 65% is obtained. The excited state
      lifetime tau at room temperature is 39 MUs. The stimulated emission cross section
      sigma(em) is 8.5*10(-20) cm2, resulting in a practical figure of merit, sigma(em)
      * tau, of 3.3*10(-24) cm2 s at room temperature. These properties suggest
      suitability as a broadband gain medium for tunable lasers and optical amplifiers.

PMID- 22466184
TI  - Infrared antireflective filtering for extreme ultraviolet multilayer Bragg
      reflectors.
AB  - An extreme ultraviolet multilayer mirror with an integrated spectral filter for
      the IR range is presented and experimentally evaluated. The system consists of an
      IR-transparent B4C/Si multilayer stack which is used both as EUV-reflective
      coating and as a phase shift layer of the resonant IR antireflective (AR)
      coating. The AR coating is optimized in our particular case to suppress CO2 laser
      radiation at a wavelength of 10.6 MUm, and a suppression of more than two orders
      of magnitude is demonstrated. The method allows high suppression over a large
      angular acceptance range, relevant for application in lithography systems.

PMID- 22466185
TI  - Autofocusing based on wavelength dependence of diffraction in two-wavelength
      digital holographic microscopy.
AB  - An autofocusing method for two-wavelength digital holographic microscopy (TWDHM)
      based on the wavelength dependence of the diffraction process is proposed. Red
      and green lights are employed for the illumination of the TWDHM, and the
      generated holograms are recorded simultaneously by a color CCD camera. Due to the
      wavelength dependency of the diffraction process, the farther the reconstruction
      plane is from the image plane, the larger the difference is between the red and
      green light distributions. Thus, the image plane can be determined by finding the
      minimum of the variation between the red and green lights on their amplitude
      distributions. The feasibility of the proposed method is demonstrated by
      simulation and experiment.

PMID- 22466186
TI  - Figure-of-merit enhancement of surface plasmon resonance sensors in the spectral
      interrogation.
AB  - We show that adding a thin dielectric layer with high refractive index on top of
      the metallic layer in surface plasmon resonance sensors in the Kretschmann
      Raether configuration in the spectral mode causes a redshift of the resonance
      wavelength, narrowing of the resonance dip, and an enhancement to the spectral
      sensitivity. Surprisingly, together with the sensitivity enhancement, the dip
      becomes much narrower and the figure of merit is considerably improved,
      particularly in the IR range.

PMID- 22466187
TI  - Experimental demonstration of microring quadrature phase-shift keying modulators.
AB  - Advanced optical modulation formats are a key technology to increase the capacity
      of optical communication networks. Mach-Zehnder modulators are typically used to
      generate various modulation formats. Here, we report the first experimental
      demonstration of quadrature phase-shift keying (QPSK) modulation using compact
      microring modulators. Generation of 20 Gb/s QPSK signals is demonstrated with 30
      MUm radius silicon ring modulators with drive voltages of ~6 V. These compact
      QPSK modulators may be used in miniature optical transponders for high-capacity
      optical data links.

PMID- 22466188
TI  - Low-threshold plasmonic lasing based on high-Q dipole void mode in a metallic
      nanoshell.
AB  - We propose a novel type of plasmonic lasing nanostructure consisting of a
      metallic shell and a gain core. We demonstrate numerically that highly localized
      void modes of such metallodielectric core-shell nanoparticles have a very high
      quality factor. We found that the dipole void mode has a lasing threshold as low
      as 128 cm(-1) at 800 nm as a result of the unique mode distribution within the
      shell, due to a maximum field enhancement around the void center. The lasing
      condition for a symmetry-reduced silver nanocup is also investigated and the low
      plasmonic lasing threshold is sustained provided that the opening angle of the
      nanocup is smaller than 10 degrees . Our proposal presents a new path toward
      plasmonic lasers with low gain threshold.

PMID- 22466189
TI  - Hyperfine aperiodic optical superlattice optimized by iterative domino algorithm
      for phase-matching engineering.
AB  - We proposed and experimentally demonstrated the iterative domino algorithm to
      optimize optical superlattice with >10(5) unit blocks to achieve arbitrary target
      phase-matching power spectrum. This scheme can achieve unprecedented overall
      conversion efficiency and spectral fidelity with extremely high computation
      efficiency.

PMID- 22466190
TI  - Optical readout method based on a narrow-strip filter for microcantilever array
      sensing.
AB  - An effective optical readout approach based on a narrow-strip filter is presented
      to detect bends of a bimaterial microcantilever focal plane array, by which light
      intensity of the image plane (CCD image sensor plane) can be increased and its
      uniformity on the image plane effectively enhanced. It reduces the noise
      equivalent temperature difference of the microcantilever focal plane array IR
      imaging system and improves uniformity of the IR images. A comparative experiment
      is designed to verify effectiveness. The experimental results show that the
      proposed method has advantages of preferable effect.

PMID- 22466191
TI  - Binary volume phase masks in photo-thermo-refractive glass.
AB  - Permanent binary phase masks with planar surfaces and high tolerance to laser
      radiation are recorded in the volume of photo-thermo-refractive glass using the
      contact copying technique and binary amplitude master masks. Conversion of a
      Gaussian beam to higher order modes is shown.

PMID- 22466192
TI  - Time-gated Cherenkov emission spectroscopy from linear accelerator irradiation of
      tissue phantoms.
AB  - Radiation from a linear accelerator induces Cherenkov emission in tissue, which
      has recently been shown to produce biochemical spectral signatures that can be
      interpreted to estimate tissue hemoglobin and oxygen saturation or molecular
      fluorescence from reporters. The Cherenkov optical light levels are in the range
      of 10(-6) to 10(-9) W/cm2, which limits the practical utility of the signal in
      routine radiation therapy monitoring. However, due to the fact that the radiation
      is pulsed, gated-acquisition of the signal allows detection in the presence of
      ambient lighting, as is demonstrated here. This observation has the potential to
      significantly increase the value of Cherenkov emission spectroscopy during
      radiation therapy to monitor tissue molecular events.

PMID- 22466193
TI  - Grism compressor for carrier-envelope phase-stable millijoule-energy chirped
      pulse amplifier lasers featuring bulk material stretcher.
AB  - We demonstrate compression of amplified carrier-envelope phase (CEP)-stable laser
      pulses using paired transmission gratings and high-index prisms, or grisms, with
      chromatic dispersion matching that of a bulk material pulse stretcher. Grisms
      enable the use of larger bulk stretching factors and thereby higher energy pulses
      with lower B-integral in a compact amplifier design suitable for long-term CEP
      control.

PMID- 22466194
TI  - Highly efficient room-temperature Yb:YAG ceramic laser and regenerative
      amplifier.
AB  - A room-temperature, diode-pumped, pulsed Yb:YAG ceramic free-running laser with a
      78% slope efficiency has been demonstrated. It has been shown that fine tuning of
      the mode diameter to the diameter of the pumped volume with a ratio of the pump
      to the mode diameter of 0.6 is important for achieving maximum laser efficiency
      with a Gaussian-like beam profile. A regenerative Yb:YAG ceramic amplifier with a
      maximum output energy of 14.5 mJ and a super-Gaussian beam profile is
      demonstrated.

PMID- 22466195
TI  - All-fiber coherent beam combining with phase stabilization via differential pump
      power control.
AB  - Coherent beam combining enables power scaling beyond the limits of single
      amplifiers. Therefore, improving the performance and simplicity of coherent
      combination techniques is of great interest for many high power applications.
      Here, we show all-fiber coherent beam combining of two ytterbium doped amplifiers
      with and without a dedicated phase actuator and a total output power up to 25 W.
      Instead of a dedicated phase actuator, we directly controlled the two ytterbium
      amplifiers to also stabilize their relative phase. We compared the performance of
      this method with phase stabilization using two piezo driven fiber stretchers. In
      both cases, power noise was dominated by the single amplifier.

PMID- 22466196
TI  - Plasmonic rainbow rings induced by white radial polarization.
AB  - This Letter presents a scheme to embed both angular/spectral surface plasmon
      resonance (SPR) in a unique far-field rainbow feature by tightly focusing
      (effective NA=1.45) a polychromatic radially polarized beam on an Au (20 nm)/SiO2
      (500 nm)/Au (20 nm) sandwich structure. Without the need for angular or spectral
      scanning, the virtual spectral probe snapshots a wide operation range (n=1-1.42;
      lambda=400-700 nm) of SPR excitation in a locally nanosized region. Combined with
      the high-speed spectral analysis, a proof-of-concept scenario was given by
      monitoring the NaCl liquid concentration change in real time. The proposed scheme
      will certainly has a promising impact on the development of objective-based SPR
      sensor and biometric studies due to its rapidity and versatility.

PMID- 22466197
TI  - Silicon nano-membrane based photonic crystal microcavities for high sensitivity
      bio-sensing.
AB  - We experimentally demonstrated photonic crystal microcavity based resonant
      sensors coupled to photonic crystal waveguides in silicon nano-membrane on
      insulator for chemical and bio-sensing. Linear L-type microcavities are
      considered. In contrast to cavities with small mode volumes, but low quality
      factors for bio-sensing, we showed increasing the length of the microcavity
      enhances the quality factor of the resonance by an order of magnitude and
      increases the resonance wavelength shift while retaining compact device
      characteristics. Q~26760 and sensitivity down to 15 ng/ml and ~110 pg/mm2 in bio
      sensing was experimentally demonstrated on silicon-on-insulator devices.

PMID- 22466198
TI  - Digital holographic interferometry based on wavelength and angular multiplexing
      for measuring the ternary diffusion.
AB  - We present a novel method for dynamical measurement of the ternary diffusion by
      using digital holographic interferometry based on wavelength and angular
      multiplexing techniques. Two laser beams with different wavelengths (lambda1=532
      nm and lambda2=473 nm) are used for the ternary diffusion measurement, and they
      are adjusted to make corresponding interference fringes in orthogonal directions
      on the CCD target. The orthogonal splitting of the fringes enables the spatial
      frequencies of each wavelength to be filtered separately in the Fourier spectrum
      of the hologram. Finally, they are reconstructed to obtain the molar
      concentration. This method is also suitable for two-phase diffusion measurement.

PMID- 22466199
TI  - Laser-filamentation-induced condensation and snow formation in a cloud chamber.
AB  - Using 1 kHz, 9 mJ femtosecond laser pulses, we demonstrate laser-filamentation
      induced spectacular snow formation in a cloud chamber. An intense updraft of warm
      moist air is generated owing to the continuous heating by the high-repetition
      filamentation. As it encounters the cold air above, water condensation and large
      sized particles spread unevenly across the whole cloud chamber via convection and
      cyclone like action on a macroscopic scale. This indicates that high-repetition
      filamentation plays a significant role in macroscopic laser-induced water
      condensation and snow formation.

PMID- 22466200
TI  - Focusing subwavelength grating coupler for mid-infrared suspended membrane
      waveguide.
AB  - A mid-infrared (mid-IR)-focusing subwavelength grating (SWG) coupler and
      suspended membrane waveguide (SMW) on a silicon-on-insulator wafer are studied.
      For a transverse-electric mode uniform SWG, finite-difference time-domain
      simulation predicts 44.2% coupling efficiency with 1 dB bandwidth of about 220 nm
      and backreflection of 0.78% at 2.75 MUm. Then the uniform SWG is curved to a
      focusing SWG using a phase-matching formula. The SMWs are analyzed by the finite
      element method and fabricated. An Er3+-Pr3+ co-doped mid-IR fiber laser is used
      for device characterization. The fabricated mid-IR SWG coupler has 24.7% coupling
      efficiency.

PMID- 22466201
TI  - Passive optical switching of photon pairs using a spontaneous parametric fiber
      loop.
AB  - We study a novel scheme named the spontaneous parametric fiber loop (SPFL),
      configured by deliberately introducing dispersive elements into the nonlinear
      Sagnac loop, and show it can function as a passive switch of photon pairs. The
      two-photon state coming out of SPFL highly depends on the dispersion induced
      phase difference of photon pairs counterpropagating in the loop. By properly
      managing the dispersive elements, the signal and idler photons of a pair with a
      certain detuning and bandwidth can be directed to the desired spatial modes of
      SPFL. If the photon pairs are used to generate heralded single photons, the SPFL
      can be viewed as a switch of single photons. Moreover, our investigation about
      the dispersion based phase modulation is also beneficial for designing all fiber
      sources of entangled photon pairs.

PMID- 22466202
TI  - Interferometric autocorrelation in the ultraviolet utilizing spontaneous
      parametric down-conversion inside an enhancement cavity.
AB  - Autocorrelation is a common method to estimate the duration of ultrashort laser
      pulses. In the ultraviolet (UV) regime it is challenging to employ the process of
      second-harmonic generation, most prominently due to absorption in nonlinear
      crystals at very short wavelengths. Here we show how to utilize spontaneous
      parametric down-conversion (SPDC) to generate an autocorrelation signal in the
      infrared (IR) for UV pulses. Our method utilizes the nth-order emission of the
      SPDC process, which occurs for low pumping powers proportional to the nth power
      of the UV intensity. Thus, counting 2n down-converted photons directly yields the
      nth-order autocorrelation. The method, now with detection of near-IR photons, is
      applied to the first direct measurement of ultrashort UV pulses circulating
      inside a UV enhancement cavity.

PMID- 22466203
TI  - Effects of refractive index changes on four-wave mixing bands in Er-doped
      photonic crystal fibers pumped at 976 nm.
AB  - An experimental study of the effects of an auxiliary 976 nm pump signal on the
      four-wave mixing parametric bands generated with a 1064 nm pump in a normal
      dispersion Er-doped photonic crystal fiber is presented. The four-wave mixing
      signal and idler bands shift to shorter and longer wavelengths, respectively,
      with increasing 976 nm pump power. It is shown that the wavelength-dependent
      resonant refractive index change in the erbium-doped core under 976 nm pumping is
      at the origin of the effect.

PMID- 22466204
TI  - Silicon photomultiplier detector for atmospheric lidar applications.
AB  - The viability and performance of using a silicon photomultiplier (SiPM) in
      atmospheric lidar applications is experimentally compared against the well
      established use of photomultiplier tubes. By using a modified lidar setup for
      simultaneous data acquisition of both types of sensors, we demonstrate that a
      SiPM can offer appropriate qualities for this specific application where the
      detection of fast, extremely low light pulses and large dynamic range signals are
      essential capabilities. The experimental results show that the SiPM has an
      appropriate behaviour offering suitable capabilities for elastic, backscatter
      aerosol lidars. To the best of our knowledge, this is the first study showing
      SiPM for atmospheric lidar applications.

PMID- 22466205
TI  - Enhancement of circular differential deflection of light in an optically active
      medium.
AB  - In this letter, we investigate the circular differential deflection of a light
      beam refracted at the interface of an optically active medium. We show that the
      difference between the angles of deviation of the two circularly polarized
      components of the transmitted beam is enhanced manyfold near total internal
      reflection, which suggests a simple way of increasing the limit of detection of
      chiro-optical measurements.

PMID- 22466206
TI  - Realizable planar gradient-index solar lenses.
AB  - The design of single element planar hemispherical gradient-index solar lenses
      that can accommodate the constraints of realistic materials and fabrication
      techniques are presented, and simulated with an extended and polychromatic solar
      source for concentrator photovoltaics at flux concentration values exceeding 1000
      suns. The planar hemispherical far-field lens is created from a near-field unit
      magnification spherical gradient-index design, and illustrated with an f/1.40
      square solar lens that allows lossless packing within a concentrator module.

PMID- 22466207
TI  - Diffraction of ultrashort optical pulses from circularly symmetric binary phase
      gratings.
AB  - The complete spatiotemporal characterization of the diffracted field of
      ultrashort pulses after passing through circularly symmetric binary phase
      diffraction gratings is carried out. The complex field is registered at different
      planes behind the gratings with an ultrashort-pulse measurement technique called
      SEA TADPOLE. Numerical simulations based on scalar diffraction theory are
      compared with the measurements.

PMID- 22466208
TI  - Tunable add/drop channel coupler based on an acousto-optic tunable filter and a
      tapered fiber.
AB  - We report a tunable add/drop channel coupler based on an acousto-optic tunable
      filter and a tapered fiber. The coupling efficiency and central wavelength of the
      add/drop channel coupler are tunable by simply tuning the power and frequency of
      the driving radio frequency signal. Further possible improvements on the
      configuration are also discussed.

PMID- 22466209
TI  - Intravascular photoacoustic imaging of lipid in atherosclerotic plaques in the
      presence of luminal blood.
AB  - Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic
      plaque composition on the basis of the optical absorption contrast between
      different tissue types. Given the high optical absorption of lipid at 1720 nm
      wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo
      using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in
      the presence of luminal blood. Strong optical absorption of lipid combined with
      low background signal from other tissues provides a high-contrast, depth-resolved
      IVPA image of lipid. The ability to image lipid at a single wavelength without
      removing luminal blood suggests that in vivo detection of lipid in
      atherosclerotic plaques using combined IVUS/IVPA imaging is possible.

PMID- 22466210
TI  - Aperiodic interferometer for six degrees of freedom position measurement.
AB  - We present a new class of interferometer system that is capable of simultaneous
      measurement of absolute position and rotation in all six degrees of freedom (DOF)
      with nanometer precision. This novel capability is due to the employment of a
      system of interference fringes that is not periodic. One of the key strengths
      offered by this new approach is that the absolute position of the system can be
      determined with a single measurement, rather than by counting fringes during
      displacement from a known location. The availability of a simultaneous
      measurement of all six DOF eliminates many problems associated with conventional
      interferometry.

PMID- 22466211
TI  - Magnetic-force-induced long-period fiber gratings.
AB  - A novel formation method of a long-period fiber grating (LPFG) based on a
      magnetic-force-induced microbend is proposed and experimentally demonstrated. The
      LPFG employs a permanent magnet that exerts transversal force to the fiber by
      attracting a steel coil spring. The transversal force causes periodic
      microbending to the fiber, and therefore the transmission wave attenuates at the
      core-to-cladding mode resonance. This device has advantages of ease of
      fabrication, reconfigurability, and available for any type of fiber.

PMID- 22466212
TI  - Observation of discrete gap solitons in one-dimensional waveguide arrays with
      alternating spacings and saturable defocusing nonlinearity.
AB  - We consider, both experimentally and theoretically, the existence and stability
      of localized, symmetric, and antisymmetric gap solitons (GSs) in binary lattices
      of identical waveguides but with alternating spacings. Furthermore, the
      properties of surface GSs at the boundary of the lattice are explored.

PMID- 22466213
TI  - Strong Brillouin suppression in a passive fiber ring resonator.
AB  - We demonstrate the passive suppression of stimulated Brillouin scattering in
      meter-length fiber-ring cavities through careful control of the fiber length.
      Experimentally we are able to demonstrate an over sixty-times increase in the
      Brillouin threshold of a 0.4 m fiber ring. This very simple suppression technique
      greatly simplifies the design of optical parametric devices based on fiber-ring
      cavities.

PMID- 22466214
TI  - Resonance in quantum dot fluorescence in a photonic bandgap liquid crystal host.
AB  - Microcavity resonance is demonstrated in nanocrystal quantum dot fluorescence in
      a one-dimensional (1D) chiral photonic bandgap cholesteric-liquid crystal host
      under cw excitation. The resonance demonstrates coupling between quantum dot
      fluorescence and the cholesteric microcavity. Observed at a band edge of a
      photonic stop band, this resonance has circular polarization due to microcavity
      chirality with 4.9 times intensity enhancement in comparison with polarization of
      the opposite handedness. The circular-polarization dissymmetry factor g(e) of
      this resonance is ~1.3. We also demonstrate photon antibunching of a single
      quantum dot in a similar glassy cholesteric microcavity. These results are
      important in cholesteric-laser research, in which so far only dyes were used, as
      well as for room-temperature single-photon source applications.

PMID- 22466215
TI  - Quasi-phase-matched DC-induced three wave mixing versus four wave mixing: a
      simulated comparison.
AB  - A comparison is made between DC-induced three-wave mixing under an on-off quasi
      phase-matching scheme and a perfectly phase-matched four wave mixing process. It
      is shown that the DC-induced process is capable of producing a significantly
      larger conversion efficiency than the four wave mixing process. Despite the fact
      that it suffers greater effects of dispersion, the enhanced growth rate of the DC
      induced process provides a conversion efficiency roughly 300* larger than that of
      four wave mixing. Over a sample length of 20 cm the DC-induced process is able to
      generate idler power more than 270 times greater than that produced by the
      equivalent four wave mixing process.

PMID- 22466216
TI  - Feasibility study of Zeeman modulation spectrometry with a hollow capillary fiber
      based gas cell.
AB  - For paramagnetic gases (e.g., O2, NO, NO2, OH) Zeeman modulation spectrometry is
      a method for spectrometric gas sensing with extraordinary selectivity. In this
      Letter it is combined with a hollow capillary based gas cell, where the gas is
      filled in long light-guiding capillary that is placed inside a toroidal coil.
      Over conventional Zeeman spectrometry this has the advantage of lower power
      consumption at long optical path length, since several loops of the hollow
      capillary fiber can be placed in the coil. Compared to wavelength modulation
      spectrometry the advantage is insensitivity to interference by multimode
      propagation in the fiber and absorption by other nonparamagnetic gases, which
      should enhance both sensor stability and sensitivity. Experimental and
      theoretical results are presented, showing the feasibility of the approach.

PMID- 22466217
TI  - Generation of 1.5 MUm emission through an upconversion-mediated looping mechanism
      in Er3+/Sc3+-codoped LiNbO3 single crystal.
AB  - Important for telecommunications, luminescence of trivalent erbium (Er) at 1.5
      MUm generally arises from a Stokes-shifted downconversion mechanism. We show that
      this luminescence following direct excitation of the 4I11/2 state is generated by
      upconversion-mediated looping process in Er3+/Sc3+-codoped LiNbO3 single crystal.
      Emissions at 1.0 and 1.5 MUm from the 4I11/2 and 4I13/2 states display linear and
      quadratic dependences on the excitation density in two separated ranges with a
      threshold of 20 W/cm2. This observation correlates with two- and four-photon
      processes in green and red upconversion emissions. The mechanism described has
      implications in the improvement of the output of 1.5 MUm luminescence.

PMID- 22466218
TI  - Nonlinear pulse propagation: a time-transformation approach.
AB  - We present a time-transformation approach for studying the propagation of optical
      pulses inside a nonlinear medium. Unlike the conventional way of solving for the
      slowly varying amplitude of an optical pulse, our new approach maps directly the
      input electric field to the output one, without making the slowly varying
      envelope approximation. Conceptually, the time-transformation approach shows that
      the effect of propagation through a nonlinear medium is to change the relative
      spacing and duration of various temporal slices of the pulse. These temporal
      changes manifest as self-phase modulation in the spectral domain and self
      steepening in the temporal domain. Our approach agrees with the generalized
      nonlinear Schrodinger equation for 100 fs pulses and the finite-difference time
      domain solution of Maxwell's equations for two-cycle pulses, while producing
      results 20 and 50 times faster, respectively.

PMID- 22466219
TI  - Intense Bessel-like beams arising from pyramid-shaped microtips.
AB  - We show both numerically and experimentally that intense, narrow, and low
      divergence beams of light are produced at the apex of dielectric pyramid-shaped
      microtips. These beams exhibit a Bessel transverse profile but are narrower than
      the usual Bessel beam, allowing for a significant enhancement of the light
      intensity inside the beam. They are generated by axicon-like structures with
      submicrometric height imprinted in glass by combining optical lithography and
      chemical etching. The resulting beams are experimentally imaged using
      fluorescence microscopy, in remarkable agreement with numerical computations.

PMID- 22466220
TI  - Caustic design in periodic lattices.
AB  - We study curved trajectory dynamics and design in discrete array settings. We
      find that beams with power law phases produce curved caustics associated with the
      fold and cusp type catastrophes. A parabolic phase produces a focus that suffers
      from spherical aberrations. More important, we find that by designing the initial
      phase or wavefront of the beam we can construct trajectories with pure power law
      caustics as well as aberration-free focusing of discrete waves.

PMID- 22466221
TI  - Subtractive imaging in confocal scanning microscopy using a CCD camera as a
      detector.
AB  - We report a scheme for the detector system of confocal microscopes in which the
      pinhole and a large-area detector are substituted by a CCD camera. The numerical
      integration of the intensities acquired by the active pixels emulates the signal
      passing through the pinhole. We demonstrate the imaging capability and the
      optical sectioning of the system. Subtractive-imaging confocal microscopy can be
      implemented in a simple manner, providing superresolution and improving optical
      sectioning.

PMID- 22466222
TI  - Singly resonant optical parametric oscillator based on adhesive-free-bonded
      periodically inverted KTiOPO4 plates: terahertz generation by mixing a pair of
      idler waves.
AB  - We implemented a singly resonant optical parametric oscillator based on adhesive
      free-bonded periodically inverted KTiOPO4 plates. It has major advantages such as
      walk-off compensation and oscillation at four wavelengths. The threshold of the
      oscillation was measured to be 8 MW/cm2, which is about a factor of 4 lower than
      that based in two separate KTiOPO4 crystals. By frequency-mixing the dual
      wavelength output in GaP stacks, we generated the terahertz radiation at 2.54
      THz. The tuning range of the terahertz output was demonstrated to be 2.19-2.77
      THz.

PMID- 22466223
TI  - Impact of bivalirudin and Genous stent in patients with acute myeloid leukemia
      undergoing emergency percutaneous coronary angioplasty for acute coronary
      syndrome [corrected].

PMID- 22466224
TI  - Formation and photoinduced processes of a self-assembled subphthalocyanine
      porphyrin-phthalocyanine supramolecular complex.
AB  - We report herein the formation and excitation energy transfer property of a
      ternary supramolecular complex of subphthalocyanine-porphyrin-phthalocyanine held
      by host-guest interactions.

PMID- 22466225
TI  - Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord
      blood leukocytes.
AB  - BACKGROUND: Arsenic is an epigenetic toxicant and could influence fetal
      developmental programming. OBJECTIVES: We evaluated the association between
      arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.
      METHODS: Drinking-water and urine samples were collected when women were at <= 28
      weeks gestation; the samples were analyzed for arsenic using inductively coupled
      plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n
      = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was
      quantified using pyrosequencing in 113 pairs of maternal and umbilical blood
      samples. We used general linear models to evaluate the relationship between DNA
      methylation and tertiles of arsenic exposure. RESULTS: Mean (+/- SD) drinking
      water arsenic concentration was 14.8 +/- 36.2 MUg/L (range: < 1-230 MUg/L).
      Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52,
      2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes,
      respectively, in association with the highest versus lowest tertile of total
      urinary arsenic per gram creatinine. Arsenic exposure was also associated with
      higher methylation of some of the tested CpG sites in the promoter region of p16
      in umbilical cord and maternal leukocytes. No associations were observed for Alu
      or p53 methylation. CONCLUSIONS: Exposure to higher levels of arsenic was
      positively associated with DNA methylation in LINE-1 repeated elements, and to a
      lesser degree at CpG sites within the promoter region of the tumor suppressor
      gene p16. Associations were observed in both maternal and fetal leukocytes.
      Future research is needed to confirm these results and determine if these small
      increases in methylation are associated with any health effects.

PMID- 22466226
TI  - Secondary headaches: secondary or still primary?
AB  - The second edition of the International Classification of Headache Disorders
      makes a distinction between primary and secondary headaches. The diagnosis of a
      secondary headache is made if the underlying disease is thought to cause headache
      or if a close temporal relationship is present together with the occurrence of
      the headache. At first glance, this may allow clearly secondary headaches to be
      distinguished from primary headaches. However, by reviewing the available
      literature concerning several selected secondary headaches, we will discuss the
      hypothesis that some secondary headaches can also be understood as a variation of
      primary headaches in the sense that the underlying cause (e.g. infusion of
      glyceryl trinitrate [ICHD-II 8.1.1], epilepsy [7.6.2], brain tumours [7.4],
      craniotomy [5.7], etc.) triggers the same neurophysiologic mechanisms that are
      responsible for the pain in primary headache attacks.

PMID- 22466227
TI  - Genotoxic effects of occupational exposure to lead and influence of polymorphisms
      in genes involved in lead toxicokinetics and in DNA repair.
AB  - Lead is still widely used in many industrial processes and is very persistent in
      the environment. Although toxic effects caused by occupational exposure to lead
      have been extensively studied, there are still conflicting results regarding its
      genotoxicity. In a previous pilot study we observed some genotoxic effects in a
      population of lead exposed workers. Thus, we extended our study analysing a
      larger population, increasing the number of genotoxicity endpoints, and including
      a set of 20 genetic polymorphisms related to lead toxicokinetics and DNA repair
      as susceptibility biomarkers. Our population comprised 148 workers from two
      Portuguese factories and 107 controls. The parameters analysed were: blood lead
      levels (BLL) and delta-aminolevulinic acid dehydratase (ALAD) activity as
      exposure biomarkers, and T-cell receptor (TCR) mutation assay, micronucleus (MN)
      test, comet assay and OGG1-modified comet assay as genotoxicity biomarkers. Lead
      exposed workers showed markedly higher BLL and lower ALAD activity than the
      controls, and significant increases of TCR mutation frequency (TCR-Mf), MN rate
      and DNA damage. Oxidative damage did not experience any significant alteration in
      the exposed population. Besides, significant influence was observed for VDR
      rs1544410 polymorphism on BLL; APE1 rs1130409 and LIG4 rs1805388 polymorphisms on
      TCR-Mf; MUTYH rs3219489, XRCC4 rs28360135 and LIG4 rs1805388 polymorphisms on
      comet assay parameter; and OGG1 rs1052133 and XRCC4 rs28360135 polymorphisms on
      oxidative damage. Our results showed genotoxic effects related to occupational
      lead exposure to levels under the Portuguese regulation limit of 70 MUg/dl.
      Moreover, a significant influence of polymorphisms in genes involved in DNA
      repair on genotoxicity biomarkers was observed.

PMID- 22466228
TI  - [IDH gene mutation in brain tumors].

PMID- 22466229
TI  - [Efficacy of indocyanine green videoangiography for carotid endarterectomy].
AB  - OBJECTIVE: The aim of the present study is to assess whether the technique of
      surgical microscope-based indocyanine green videoangiography (ICG-VA) and the
      FLOW800 system are efficient for hemodynamic evaluation during carotid
      endarterectomy (CEA). METHODS: 20 CEAs for 19 patients were performed from
      January to July 2011. Before and after endarterectomy, ICG was injected
      intravenously. After the procedure, ICG-VA was analyzed by FLOW800. Regions of
      interest were the common carotid artery, the plaque, the internal carotid artery,
      and the external carotid artery to evaluate changes in each intensity value.
      RESULTS: The distal end of carotid plaque and the proximal end were identified in
      85% of CEAs and 78.9% of cases. In 5 cases (26.3%) with more severe stenosis
      (>90%), the decrease of blood flow intensity in the internal carotid artery was
      delayed before endarterectomy. After endarterectomy, the finding was improved in
      all the 5 cases. After the endarterectomy, the intensity values in the common
      carotid artery, the plaque, the internal carotid artery, and the external carotid
      artery had increased 162 +/- 129, 337 +/- 212, 139 +/- 151 and 177 +/- 143.
      Especially in the value of the plaque, there was a great improvement.
      CONCLUSIONS: ICG-VA provides information of the plaque location and the patency
      of the arterial vessel during CEA. Using FLOW800, semiquantitive information of
      hemodynamics was able to be acquired, especially for the case of severe stenosis
      with collapse of the internal carotid artery.

PMID- 22466230
TI  - [Surgical method for lumbar foraminal stenosis].
AB  - OBJECTIVE: There are mainly two surgical methods for lumbar foraminal stenosis,
      simple decompression of the extra-foraminal portion or decompression with
      fixation surgery. However the indication of either method is controversial. The
      aim of this study is to show our surgical method and results. METHOD: In six
      cases diagnosed as lumbar foraminal stenosis with or without far lateral disc
      herniation by X-ray, CTscan, MRI and nerve conduction velocity, decompression
      surgery was performed by our paramedian method (Wiltse approach). The apex and
      lateral portion of the superior articular facet (one third to one fourth) and the
      transforaminal ligament without fixation for lumbar foraminal stenosis. All
      patients were followed up for more than 10 months after the surgery. Japanese
      Orthopaedic Association (JOA) score and Visual Analogue Scale (VAS) were assessed
      before surgery and more than 10 months after the surgery. Postoperative
      radiological assessments were examined by neutral, flexion and extension X-ray.
      RESULT: Foraminal stenosis was successfully decompressed in all cases. The
      postoperative JOA score and VAS were significantly improved in comparison to the
      preoperative score (Recovery Rate ware of 74.9% and 85.8%). There was no
      recurrence of symptoms or necessity for secondary surgery. The radiological
      evaluation did not indicate significant instability or decrease in the disc
      height. CONCLUSION: Our surgical method, removing the apex and lateral part of
      the superior articular process and transforaminal ligament without fusion led to
      a good outcome and recurrence 10 months after the surgery had not occurred.

PMID- 22466231
TI  - [Dual lead spinal cord stimulation using octad lead for central post-stroke
      pain].
AB  - Spinal cord stimulation (SCS) has become the preferred option for neurosurgical
      management of several intractable pains. To evaluate effects of dual lead SCS
      using two quad leads for central post-stroke pain (CPSP), we retrospectively
      reviewed eight consecutive patients with CPSP who underwent SCS. Six (75%) of
      eight patients obtained more than 50% pain relief during test stimulation, and
      the efficacies continued for about 12 months in five (83%) of six patients. There
      were no significant complications. SCS is less invasive neurostimulation
      treatment and provides pain relief for some cases of CPSP.

PMID- 22466233
TI  - [Neuromyelitis optica spectrum disorder: a case report].
AB  - Neuromyelitis optica (NMO) is a relapsing inflammatory disease of the central
      nervous system, usually affecting the optic nerves and the spinal cord. It is
      presumed to be an antibody-mediated disorder and the target antigen is the water
      channel aquaporin-4 (AQP4) on astrocyte cell membranes. NMO is a disease caused
      by astrocyte disorder and is distinct from multiple sclerosis (MS), which is a
      primarily demyelinating disease caused by oligodendrocyte disorder. In NMO,
      spinal MRI shows a T2-hyperintense, longitudinally extensive (>= 3 vertebral
      segments) spinal cord lesion. The case, which has optic neuritis or transverse
      myelitis with the presence of AQP4 antibody, is called as NMO spectrum disorder.
      A 68 year-old woman with a history of hypertension and diabetes mellitus was
      brought to the former hospital by ambulance with acute onset of tetraparesis. She
      denied visual acuity disturbance. MRI revealed a T2-hyperintense lesion from C5
      to T2 level. Laboratory examination showed the presence of AQP4 antibody and the
      absence of oligoclonal bands. Low-dose steroid treatment was started after
      establishing a diagnosis of NMO. She incompletely recovered from disability,
      although the T2-hyperintense lesion on MRI had almost disappeared six months
      after the onset. It is important to maintain a high index of suspicion for NMO in
      cases with a longitudinally extensive spinal cord lesion, because untreated NMO
      leads to severe disability.

PMID- 22466232
TI  - [Four cases of fusiform posterior inferior cerebellar artery aneurysms
      successfully treated by trapping and occipital artery-PICA bypass].
AB  - Aneurysms located on the proximal portion of the posterior inferior cerebellar
      artery (PICA) are rare, and even rarer are fusiform aneurysms in this location.
      Therefore the principles of surgical management are poorly understood and still
      subject to debate. The management plan for these lesions is based on the proper
      understanding of the PICA anatomy, and particularly the origin of important
      perforating arteries. As many anatomic variations of PICA can be observed and the
      perforator's origin is sometimes in complex anatomical relations with the
      aneurysm, the management has to be individualized in each case. The objective of
      management is to exclude of the aneurysm from the circulation while preserving
      the perforator and distal flow. We report four cases of PICA fusiform aneurysms
      of the anterior or lateral medullary segments which were treated successfully
      with trapping of the abnormal arterial segment and distal revascularization of
      PICA. Trapping was adjusted to the specific anatomical circumstances in each
      case, preserving perforators to the maximum and revascularizing (OA-distal PICA)
      distal territory.

PMID- 22466234
TI  - [Leptomeningeal carcinomatosis following 27 years remission from breast cancer
      with epidermoid: a case report].
AB  - We herein report a patient with leptomeningeal carcinomatosis (LC) in long-term
      remission from breast cancer, co-existing with a posterior fossa epidermoid and
      an increase in the serum CA19-9 level which complicated the diagnosis. A 59-year
      old woman underwent a left mastectomy due to breast cancer 27 years ago. She was
      admitted to our hospital suffering from a headache and diplopia. Her serum CA19-9
      level on admission was elevated, and diffusion weighted images showed a high
      intensity tumor in the prepontine and left cerebello-pontine cistern. A left
      lateral suboccipital craniotomy with endoscopic assistance was performed for
      tissue sampling. The pathological diagnosis was an epidermoid and LC from breast
      cancer. She died of progression of leptomeningeal carcinomatosis 31 days after
      surgery. LC alone following long-term remission from breast cancer is extremely
      rare. Meningeal irritation co-existing with an epidermoid mimicking chemical
      meningitis is even rarer. Pathological confirmation is required for such rare
      cases.

PMID- 22466235
TI  - [Hemangiopericytoma on the intradural thoracic spinal cord: a case report].
AB  - Hemangiopericytoma develops from many organs. In the central nervous system, most
      tumors arise in the intracranial portion, and tumors originating from the spinal
      cord are rare. Its clinical course and neurological characteristics have not been
      disclosed. We present a case of a 51-year-old woman with gradually progressing
      paraparesis. Magnetic resonance (MR) images of the thoracic spine demonstrated an
      intradural tumor at the 6 and 7 thoracic vertebral body level. The patient
      underwent total excision of the tumor. The histological diagnosis was
      hemangiopericytoma. MR images after the operation showed no residual tumor and
      the patient was followed up without adjuvant therapy. However, 5 years later, the
      patient complained of back pain and gait disturbance again, and MR images showed
      a recurrence of the tumor. We resected the tumor under motor evoked potential
      (MEP) monitoring and removed the extradural part of the tumor, but the part of
      the tumor which had infiltrated the spinal cord was left due to the lowering of
      MEP amplitude. The operation resulted in partial resection. Spinal intradural
      hemangiopericytoma is very rare, and only 15 cases including the present case
      have been reported. This paper will discuss the clinical characteristics and
      treatment for this tumor.

PMID- 22466236
TI  - [A case of cervicothoracic subpial lipoma].
AB  - We report the case of a 24-year-old woman with cervicothoracic subpial lipoma not
      associated with spinal dysraphism. She complained of back pain, gait disturbance,
      and sensory disturbance of the both lower extremities. MRI revealed a
      hyperintense mass lesion that was dorsolateral to the spinal cord in the
      intradural region between C7 and Th4 on both T1 and T2 weighted images. Axial T2
      weighted images showed dorsal nerve roots passing through the mass. A thoracic
      laminectomy between Th1 and Th4 was performed. A yellowish subpial mass was found
      after the dura was opened, and the borderline between the tumor and the normal
      spinal cord was unclear. The mass was partially resected and intraoperative SEP
      monitoring data remained unchanged. Dural plasty using artificial dura was
      performed. Histological examination revealed mature adipose and connective
      tissues, a fact which was compatible with a diagnosis of lipoma. Postoperatively,
      no complications occurred. The patient's gait disturbance and hypesthesia of the
      right lower extremity slightly improved. Subpial spinal lipoma not associated
      with dysraphism is rare and accounts for only 1% of all spinal tumors. A slow
      ascending spastic monoparesis or paraparesis is a common initial symptom.
      However, once symptoms progress, further deterioration is rapid. Therefore, early
      surgical decompression and debulking of the subpial lipoma in patients with
      neurological abnormalities is recommended because most symptomatic patients do
      not improve after surgery.

PMID- 22466237
TI  - [Systematic review of complications for proper informed consent. Surgery for
      unruptured internal carotid artery aneurysm].

PMID- 22466238
TI  - Prospects of cancer biotherapy.

PMID- 22466239
TI  - Anti-aging effects of oligomeric proanthocyanidins isolated from persimmon
      fruits.
AB  - Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated
      senescence, shows age-related deficits in learning and memory. The oral
      administration of oligomers improved spatial and object recognition impairment in
      SAMP8. The expression of phosphorylated neurofilament-H was significantly
      elevated in the hippocampal CA1. This indicates that oligomers induce an increase
      in the density of axons. To investigate the protective mechanisms of oligomers
      against brain dysfunction with aging, we carried out a receptor tyrosine kinase
      phosphorylation antibody array, and clarified that the administration of
      oligomers led to an increase in the phosphorylation of vascular endothelial
      growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of
      oligomers. The phosphorylation of VEGFR-2 was more markedly increased in the
      hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in
      oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist.
      Elucidating the relationship between memory impairment with aging and VEGFR-2
      signaling may provide new suggestions for protection against memory deficit in
      the aging brain. In addition, we revealed that the administration of oligomers
      extended the life span of SAMP8. Oligomers elevated SIRT1 expression, which is
      recognized as an essential factor for life span extension in the brain. However,
      the administration of oligomers did not induce stereotypical behaviors such as
      rearing, jumping, or hanging from the lid of a cage, while food restriction
      increased these frequencies without a significant change in motor function. The
      present study suggests the promising role of oligomers as an anti-aging agent to
      extend life span.

PMID- 22466240
TI  - A low-dose combination of valsartan and low molecular weight heparin better
      improved glomerular permeability than did high-dose monotherapy in rats with
      diabetic nephropathy.
AB  - Diabetic nephropathy is the most common and severe renal complication of diabetes
      mellitus. The present study sought to investigate the renoprotective effects of a
      combination therapy of valsartan and low molecular weight heparin (LMWH) in rats
      with diabetic nephropathy induced by uninephrectomy and streptozotocin. The
      animals were divided into five groups as follows: sham-operated rats, diabetic
      control rats, diabetic rats treated with 20 mg/kg/day valsartan, diabetic rats
      treated with 600 IU/kg/day LMWH, diabetic rats treated with a combination of
      valsartan and LMWH (valsartan 10 mg/kg/day and LMWH 300 IU/kg/day). The treatment
      regimen was maintained for 8 weeks. Treatment with valsartan, LMWH, or a
      combination of the two had no significant effect on blood glucose levels.
      However, the urine protein excretion levels significantly decreased for the three
      drug treatment groups; the most dramatic decreases were observed in the
      combination treatment group. Kidney histology was examined using periodic acid
      Schiff staining and immunohistochemical staining of extracellular matrix
      proteins. Results indicated that histopathology improved markedly in the three
      drug treatment groups; combination therapy had an equal or better effect than
      monotherapy in terms of decreasing the abnormal thickness of the glomerular basal
      membrane, the ratio of the area of the mesangial region with respect to the total
      area of renal glomeruli, and the accumulation of collagen IV and laminin in
      kidney tissue. In addition, serum levels of transforming growth factor-beta1 (TGF
      beta1) also markedly decreased in the drug treatment groups according to ELISA.
      However, there were no significant differences between the combination therapy
      group and monotherapy group. These results suggest that a combination of
      valsartan and LMWH at half the dose used in monotherapy is better at improving
      glomerular permeability in rats with diabetic nephropathy.

PMID- 22466241
TI  - Hemocytes and humoral factors in silkworm blood are cooperatively involved in
      sheep erythrocyte aggregation.
AB  - Sheep red blood cells (SRBCs) rapidly aggregated when injected into the blood
      (hemolymph) of living silkworms. SRBCs also rapidly aggregated when incubated
      with hemolymph in vitro. SRBCs did not aggregate when incubated with single
      hemolymph components, hemocytes and cell-free plasma separated by centrifugation,
      whereas incubation with the mixture of components induced SRBC aggregation,
      suggesting that both hemocytes and plasma are required for the reaction.
      Treatment of hemocytes with sodium azide inhibited SRBC aggregation. On the other
      hand, SRBCs pre-incubated with hemocytes aggregated in the plasma, even in the
      presence of sodium azide. SRBC aggregation was not observed when the SRBCs were
      physically separated from the hemocytes by a polycarbonate filter. These findings
      suggest that SRBCs are directly attacked by hemocytes and become sensitive to
      humoral factors that cause SRBC aggregation.

PMID- 22466242
TI  - Arabino-mycolates derived from cell-wall skeleton of Mycobacterium bovis BCG as a
      prominent structure for recognition by host immunity.
AB  - Arabino-mycolates are components of the cell-wall skeleton of Mycobacterium bovis
      BCG (BCG-CWS). It is known that synthesized arabinomycolates induce the
      production of tumor necrosis factor alpha (TNF-alpha) in murine macrophage cell
      lines at an intensity similar to that of BCG-CWS. However the immunological
      activity of natural arabino-mycolates isolated from BCG has not been
      investigated, probably due to the complexity of the molecule. In this paper, we
      investigated the immunostimulatory activity of arabino-mycolates isolated from
      BCG-CWS by acid hydrolysis. Arabino-mycolates obtained by acid hydrolysis from
      the originally prepared CWS (SMP-105) of M. bovis BCG Tokyo 172 strain consisted
      mainly of mono-arabinose mono-mycolate, penta-arabinose tetra-mycolate and hexa
      arabinose tetramycolate fractions. Arabino-mycolates significantly induced TNF
      alpha production with an intensity comparable to that of CWS and enhanced delayed
      type hypersensitivity (DTH) reactions against inactivated tumor cells. Arabino
      mycolates-induced TNF-alpha production was completely dependent on TLR2 and MyD88
      pathways. These findings indicate that isolated natural arabino-mycolates possess
      potent adjuvant immunostimulatory activity.

PMID- 22466243
TI  - Mechanisms of vincristine-induced neurotoxicity: Possible reversal by
      erythropoietin.
AB  - Vincristine (VCR) is a potent anticancer drug, but neurotoxicity is one of its
      most important dose-limiting toxicities. In this study, we investigated the
      neurotoxic effect of VCR, the possible mechanisms and the role of erythropoietin
      (EPO) in the protection against VCR-induced neurotoxicity in a rat model. The
      neurotoxicity of VCR and protective effect of EPO were examined using the tail
      flick test and by recording electrophysiological characteristics in isolated
      sciatic nerve. To elucidate the underlying mechanisms, mRNA expression of N
      methyl-D-aspartate (NMDA) receptor, an index of glutamate excitotoxicity, and
      calcitonin gene-related peptide (CGRP), an important regulator of vascular tone,
      were measured in both spinal cord and sciatic nerves using an RT-PCR method.
      After intraperitoneal injection at a dose of 150 MUg/kg three times weekly for
      five consecutive weeks, VCR significantly decreased the latency of tail
      withdrawal reflex, the amplitude of maximum compound action potential (MCAP) and
      chronaxie, and prolonged the duration of action potential (AP) and relative
      refractory period (RRP), but it had no effect on conduction velocity. VCR
      increased NMDA receptor expression and decreased CGRP expression. Forty MUg/kg of
      EPO improved all VCR-induced changes, except chronaxie, while a higher dose of 80
      MUg/kg reversed all parameters and its effect was more prominent on tail flick
      test latency and NMDA receptor expression. These results suggested that VCR might
      cause increased nerve excitability and induce a state of glutamate excitotoxicity
      through enhancing NMDA receptor expression and diminishing CGRP expression, thus
      resulting in axonal degeneration. EPO had an obvious neuroprotective effect
      probably through decreasing NMDA receptor expression and increasing CGRP
      expression both centrally and peripherally.

PMID- 22466244
TI  - Antityrosinase and antioxidant activities of essential oils of edible Thai
      plants.
AB  - This work was undertaken to explore antityrosinase and antioxidant activities of
      twenty essential oils of edible Thai plants. Antityrosinase activity against
      mushroom tyrosinase was examined by means of the dopachrome method using L-dopa
      as an enzymatic substrate. The essential oil of Cymbopogon citratus had the
      highest level of antityrosinase activity, followed by that of Ocimum canum with
      enzymatic inhibition of 69 +/- 4 and 66 +/- 3%. GC-MS revealed that geranial and
      neral were the two most abundant components of their chemical compositions.
      Antioxidant activity was gauged by the free radical scavenging activity test and
      ferric reducing/antioxidant power assay. The essential oil of Ocimum sanctum had
      the highest level of antioxidant activity, followed by the essential oil of
      Ocimum gratissimum. These results led to the conclusions that the essential oils
      of edible Thai plants exhibit important biological activities and are a promising
      choice as natural active ingredients because of their antityrosinase and
      antioxidant activities.

PMID- 22466245
TI  - Emulsions and rectal formulations containing myrrh essential oil for better
      patient compliance.
AB  - Myrrh has long been used for its circulatory, disinfectant, analgesic,
      antirheumatic, antidiabetic, and schistosomicidal properties. Myrrh essential oil
      (MEO) was extracted from the oleo-gum resin of Commiphora molmol and formulated
      into emulsions and suppositories to mask/avoid its bitter taste. Three oil-in
      water emulsions (E1-E3) were formulated and taste was evaluated by 10 volunteers.
      Particle size distribution was measured and correlated with excipients and the
      method of preparation. Physical and chemical stability testing was carried out
      for the optimum formulation (E2). Seven suppository formulations were
      investigated (F1-F7). Suppocire AML (F1) and Suppocire CM (F2) were chosen as
      fatty bases, and polyethylene glycol (PEG) 1500 (F3), PEG 4000 (F4), and a PEG
      blend (50% PEG 6000 + 30% PEG 1500 + 20% PEG 400) (F5) were chosen as water
      soluble bases. A blend of PEG 1500 and Suppocire CM was also used (F7). Camphor
      (5%) was added to PEG 1500 (F6). Disintegration time, release rate, DSC, fracture
      points, and weight uniformity were evaluated. The overall average bitterness for
      formulations E1, E2, and E3 was 6.44, 4.15, and 3.45, respectively. Suppositories
      containing Suppocire AML had the fastest disintegration time (1.5 min) with
      dissolution efficiency (DE) of 56.8%. F3 containing PEG 1500 had a fast
      disintegration time of 2.5 min and maximum DE of 93.5%. The PEG blend had
      satisfactory release: (DE = 90.9%). A mixed fatty and water-soluble base (F7) had
      a disintegration time of 5 min and low DE (33.4%). A stable MEO emulsion with
      acceptable taste was formulated to improve patient acceptance and compliance. F3
      suppositories yielded satisfactory results, while formulations containing
      fatsoluble bases exhibited poor release.

PMID- 22466248
TI  - Morphological analysis of the maxillary arch and hard palate in edentulous
      maxilla of South Indian dry skulls.
AB  - PURPOSE: The purpose of this study is to demonstrate the role of
      aging?edentulousness on the maxillary arch, the size of the alveolar process, the
      shape and thickness of the hard palate in the South Indian dry skulls to
      customize more appropriate treatment of elderly edentulous patients. METHODS: One
      hundred dry skulls were divided into dentate and edentulous groups and were
      subgrouped into male and female. They were subjected to various morphological and
      morphometrical analyses. RESULTS: The data have revealed a more significant
      reduction in the depth and width (p < 0.001) of the arch corresponding to the
      reduction in the size and thickness of the alveolar process (p < 0.001) in the
      edentulous skull. Further, a significant reduction in the size and thickness (p <
      0.001) of the hard palate was observed in the edentulous skull. The data clearly
      indicate the effect of tooth loss in the horizontal regression of the maxilla.
      Furthermore, it may enhance the bone resorption that can ultimately result in the
      marked reduction of the width and depth of the alveolar arch concomitant with the
      alteration of the hard palate. These changes may subsequently alter the facial
      appearance in the elderly population. CONCLUSION: The observed data from specific
      group of population may provide relevant data for their comparative analysis
      between different populations for a better understanding of their regional
      differences with respect to environmental and social influence. Moreover, the
      data can provide a better idea to evaluate a promising treatment strategy in
      prosthodontics and orthodontics in South India.

PMID- 22466249
TI  - Increasing screening mammography among immigrant and minority women in Canada: a
      review of past interventions.
AB  - Screening mammograms are important to detect breast cancer at earlier and more
      treatable stages. Immigrant and minority women report low participation rates due
      to barriers related to cultural beliefs and norms, privacy/modesty, and language.
      This review examines whether screening mammogram interventions in Canada and
      other countries with comparable health-care systems have addressed the needs of
      these women. Our systematic literature search identified studies that focused on
      increasing screening mammogram participation among immigrant and/or minority
      women. We used the Health Belief Model and the PRECEDE-PROCEED Model to guide our
      critical synthesis of the reviewed interventions and the recommendations for the
      future. Eight studies met the search criteria. Overall, interventions showed some
      increase in mammogram participation rates. The barriers targeted were relatively
      similar across studies and there was a focus on increasing cues to screening.
      This review illustrates that it is essential to develop and implement programs to
      overcome the unique barriers to screening mammography if we are to increase
      participation among immigrants and minority women. We suggest other potentially
      effective health promotion strategies as a starting point for discussion and
      future research.

PMID- 22466250
TI  - Occupational skin diseases in Czech healthcare workers from 1997 to 2009.
AB  - BACKGROUND: The healthcare sector ranked in second place among economic sectors
      in the Czech Republic, with about 11.4 % of all occupational diseases in 2009.
      Skin diseases constituted about 20 % of all occupational diseases. OBJECTIVES:
      The aim of this study was to analyze the causes and trends in allergic and
      irritant-induced skin diseases in the healthcare sector. METHODS: The data
      concerning occupational skin diseases (Chapter IV of the Czech List of
      Occupational Diseases, non-infectious skin illnesses) in the healthcare sector
      were analyzed from the Czech National Registry of Occupational Diseases from 1997
      until 2009. The trends in the total counts and most frequent causes were
      evaluated. RESULTS: During the past 13 years, a total of 545 skin diseases were
      acknowledged in healthcare workers. Allergic contact dermatitis was diagnosed in
      464 (85 %), irritant contact dermatitis in 71 (13 %) and contact urticaria in 10
      subjects (2 %). Ninety-five percent of the patients were females. The overall
      incidence in individual years varied between 1.0 and 2.9 cases per 10,000 full
      time employees per year. Disinfectants were the most frequent chemical agents
      causing more than one third of all allergic skin diseases (38 %), followed by
      rubber components (32 %) and cleaning agents (10 %). CONCLUSION: A general
      downward trend of diagnosed cases of occupational skin diseases in heath care
      workers in the Czech Republic over the past 13 years was demonstrated.

PMID- 22466251
TI  - Climate change impact on the olive pollen season in Mediterranean areas of Italy:
      air quality in late spring from an allergenic point of view.
AB  - Recent studies have shown that there are many effects of climate change on
      aeroallergens, and thus on allergic diseases in humans. In the Mediterranean
      region, despite the importance of the olive tree for production, there is high
      allergenicity of olive pollen and related risks to human health. Aerobiological
      sampling techniques can be used to analyse the pollinosis phenomenon through
      determination of mean daily pollen concentrations per cubic metre of air. The
      present study was carried out from 1999 to 2008 in 16 olive-growing areas in
      Italy, to update the information on the pollinosis characteristics of Olea
      europaea in the study areas. The analysis of the average flowering season over
      the study period highlights a temporal scaling of pollen in the atmosphere that
      depends on the different climatic characteristics. This is mainly dependent on
      temperature, and in part, determined by latitude. Generally, the levels of O.
      europaea pollen in the atmosphere are higher from mid-April to the end of June,
      with the period of greatest risk to human health due to this olive pollen in this
      area currently limited primarily to the last 10 days of May. However, the pollen
      season can move, depending on the climate scenario considered, and data here can
      be used to determine potential time shifts in pollinosis that might cause more
      precocious asthma and allergy problems. The allergy season for this type of
      pollen might be significantly precocious in future decades (20-30 days earlier in
      the year), which will impact on the severity and duration of allergies
      attributable to olive tree pollen.

PMID- 22466252
TI  - Photoinduced electron transfer and solvation dynamics in aqueous clusters:
      comparison of the photoexcited iodide-water pentamer and the water pentamer
      anion.
AB  - Upon photoexcitation of iodide-water clusters, I(-)(H(2)O)(n), an electron is
      transferred from iodide to a diffuse cluster-supported, dipole-bound orbital.
      Recent femtosecond photoelectron spectroscopy experiments have shown that, for
      photoexcited I(-)(H(2)O)(n) (n>= 5), complex excited-state dynamics ultimately
      result in the stabilization of the transferred electron. In this work, ab initio
      molecular dynamics simulations of excited-state I(-)(H(2)O)(5) and (H(2)O)(5)(-)
      are performed, and the simulated time evolution of their structural and
      electronic properties are compared to determine unambiguously the respective
      roles of the water molecules and the iodine atom in the electron stabilization
      dynamics. Results indicate that, driven by the iodine-hydrogen repulsive
      interactions, excited I(-)(H(2)O)(5) rearranges significantly from the initial
      ground-state minimum energy configuration to bind the excited electron more
      tightly. By contrast, (H(2)O)(5)(-) rearranges less dramatically from the
      corresponding configuration due to the lack of the same iodine-hydrogen
      interactions. Despite the critical role of iodine for driving reorganization in
      excited I(-)(H(2)O)(5), excited-electron vertical detachment energies appear to
      be determined mostly by the water cluster configuration, suggesting that
      femtosecond photoelectron spectroscopy primarily probes solvent reorganization in
      photoexcited I(-)(H(2)O)(5).

PMID- 22466253
TI  - Correlative Light-Ion Microscopy for biological applications.
AB  - Here we report a new technique, Correlative Light-Ion Microscopy (CLIM), to
      correlate SEM-like micrographs with fluorescence images. This technique presents
      significant advantages over conventional methods in enabling topographical and
      biochemical information to be correlated with nanoscale resolution without
      destroying the fluorescence signal. We demonstrate the utility of CLIM for a
      variety of investigations of cell substrate interactions validating its potential
      to become a routine procedure in biomedical research.

PMID- 22466247
TI  - Low back pain.
AB  - The Orthopaedic Section of the American Physical Therapy Association (APTA) has
      an ongoing effort to create evidence-based practice guidelines for orthopaedic
      physical therapy management of patients with musculoskeletal impairments
      described in the World Health Organization's International Classification of
      Functioning, Disability, and Health (ICF). The purpose of these low back pain
      clinical practice guidelines, in particular, is to describe the peer-reviewed
      literature and make recommendations related to (1) treatment matched to low back
      pain subgroup responder categories, (2) treatments that have evidence to prevent
      recurrence of low back pain, and (3) treatments that have evidence to influence
      the progression from acute to chronic low back pain and disability.

PMID- 22466254
TI  - Stability of an aqueous quadrupole micro-trap.
AB  - The recently demonstrated functionality of an aqueous quadrupole micro- or nano
      trap opens a new avenue for applications of Paul traps, like confinement of a
      charged biomolecule which requires a water environment for its chemical
      stability. Besides the strong viscosity forces, the motion of a charged particle
      in the aqueous trap is subject to dielectrophoretic and electrophoretic forces.
      In this study, we describe the general conditions for stability of a charged
      particle in an aqueous quadrupole trap. We find that for typical micro-trap
      parameters, the effects of both dielectrophoresis and electrophoresis
      significantly influence the trap stability. In particular, an aqueous quadrupole
      trap could play the role of a synthetic virtual nanopore for the third generation
      of DNA sequencing technology.

PMID- 22466255
TI  - Aichi virus infection in elderly people in Sweden.
AB  - Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with
      gastroenteritis in humans. Previous studies have shown high seroprevalence but
      low incidence (0.9-4.1%) in clinical samples. We report here the first detection
      of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients
      with diarrhea, who were negative for other enteric viruses, were included in the
      study. AiV were detected in three specimens, all from elderly patients.
      Phylogenetic analysis revealed that the three Swedish isolates belonged to
      genotype A and were genetically closest to European and Asian strains of AiV.

PMID- 22466256
TI  - Development of Noxa-like BH3 mimetics for apoptosis-based therapeutic strategy in
      chronic lymphocytic leukemia.
AB  - Despite real advances made in chemoimmunotherapy, chronic lymphocytic leukemia
      (CLL) is still an incurable disease. New therapeutic strategies based on the
      restoration of the cell death program seemed relevant. Some members of the Bcl-2
      family are critical players in the defective apoptotic program in CLL cells
      and/or targets of apoptosis inducers in vitro. The concept of BH3 mimetics has
      led to the characterization of small molecules mimicking proapoptotic BH3-only
      members of the Bcl-2 family by their ability to bind and antagonize the
      prosurvival members. Some putative or actual BH3 mimetics are already being
      tested in clinical trials with somewhat promising results. However, none of them
      has a high enough interaction affinity with Mcl-1, a crucial antiapoptotic factor
      in CLL. It has been suggested that resistance to BH3 mimetics can be overcome by
      using inhibitors of Mcl-1 expression. An alternative and more direct strategy is
      to design mimetics of the Noxa BH3 domain, which is a specific antagonistic Mcl-1
      ligand. The development of such Noxa-like BH3 mimetics, capable of directly
      interacting with Mcl-1 and efficiently neutralizing its antiapoptotic activity,
      is extremely important to evaluate their impact on the clinical outcome of
      patients with CLL.

PMID- 22466257
TI  - Genome-wide identification of structural variants in genes encoding drug targets:
      possible implications for individualized drug therapy.
AB  - OBJECTIVE: The objective of the present study was to identify structural variants
      of drug target-encoding genes on a genome-wide scale. We also aimed at
      identifying drugs that are potentially amenable for individualization of
      treatments based on knowledge about structural variation in the genes encoding
      their targets. METHODS: Information about human drug targets of all therapeutic
      drugs and nutraceuticals approved by the Food and Drug Administration and with an
      Anatomical Therapeutic Chemical (ATC) code, namely, 876, was obtained from the
      DrugBank and applied to interrogate the Database of Genomic Variants. RESULTS: We
      identified 1721 structural variants, which affected 495 of 1005 different genes
      encoding drug targets. About 70% of the Food and Drug Administration-approved
      drugs had targets subjected to structural variation, in particular copy number
      variation. The distribution of drugs with targets encoded by copy number variable
      genes differed between ATC groups with pronounced over-representation in ATC
      group N, that is, nervous system drugs (P=3.75e-5). Several narrow therapeutic
      index drugs with targets subjected to genomic structural variation were
      identified. Information about the frequencies of the structural variants and drug
      consumption allowed us to identify potential candidates for implementation in
      pharmacogenetic testing and individualized drug treatments. CONCLUSION:
      Structural variants in pharmacodynamic genes may play a larger role in
      determining individual variation in drug responses than currently believed.
      Inclusion of such genes in pharmacogenetic testing holds promising prospects as
      they may have large effect sizes.

PMID- 22466259
TI  - An electrochemical immunosensor for ochratoxin A determination in wines based on
      a monoclonal antibody and paramagnetic microbeads.
AB  - We report a direct competitive immunosensor for the rapid determination of
      ochratoxin A (OTA) in wine samples. Magnetic beads (1 +/- 0.5 MUm diameter)
      covered with streptavidin were functionalized with a monoclonal antibody against
      OTA, and then left to incubate in a solution of tracer (ochratoxin conjugated to
      the enzyme peroxidase) and a range of OTA concentrations (10(-4) to 1,000 ng mL(
      1)). After washing and separation steps helped with a magnetic field, a volume of
      the dispersion was put on screen-printed electrodes under a magnet, and after
      adding the substrate the p-benzoquinone generated enzymatically was detected by
      differential-pulse voltammetry. Wine samples (2 mL) were easily prepared simply
      by adjusting to pH = 7.5 with diluted NaOH and by adding polyvinylpyrrolidone for
      complexing polyphenols, without any other clean-up or preconcentration steps. The
      limit of detection for detecting OTA in wines was of 0.11 +/- 0.01 ng L(-1), well
      below the permitted content of the mycotoxin by the European Union (<2 ng mL(
      1)). Spiked wines were subjected to immunosensor calibrations to study the matrix
      effects. OTA concentrations measured with the immunosensor were compared with
      those obtained by high-performance liquid chromatography coupled to fluorescence
      detection (AOAC official method 2001.01). The OTA levels from two red wines of
      "Campo de Borja", Spain, ranged from about 0.027 to 0.033 ng mL(-1) of OTA.

PMID- 22466260
TI  - The electrical basis of bioimpedance.

PMID- 22466261
TI  - Lupus nephritis: in search of a better future.

PMID- 22466262
TI  - Association of C49620T ABCC8 polymorphism with anthropometric and metabolic
      parameters in patients with autosomal dominant polycystic kidney disease: a
      preliminary study.
AB  - BACKGROUND: The aim of the study was to evaluate an association between the
      C49620T ABCC8 gene polymorphism and anthropometric, biochemical parameters,
      pancreatic beta-cell function and insulin sensitivity among autosomal dominant
      polycystic kidney disease (ADPKD) patients. METHODS: Forty-nine ADPKD patients
      (M/F: 19/30) and fifty healthy controls (M/F: 22/28) aged above 18 years, with
      normal kidney function and no diagnosis of diabetes, were enrolled into the
      study. The ABCC8 (SUR1) C49620T (IVS15-3C/T, rs1799854) genotypes were determined
      using a PCR-RFLP technique. RESULTS: In the ADPKD group among TT homozygous
      patients, total body fat content and percentage of fat in body weight were
      significantly lower than among C allele carriers (16.1 +/- 7.7 vs 22.9 +/- 7.1kg,
      p=0.04 and 22.8 +/- 6.5 vs 30.0 +/- 6.1%, p=0.001, respectively) while total body
      water was higher (58.4 +/- 4.3 vs 53.7 +/- 4.0kg, p=0.003). Among TT homozygous
      controls higher BMI values and LDL-cholesterol levels were observed if compared
      to C variant carriers (26.3 +/- 3.9 vs 23.8 +/3.4kg/m2 p=0.04 and 133.1 +/- 27.0
      vs 114.3 +/- 35.2mg/dL, p=0.05, respectively), as well as higher area under curve
      of glucose concentrations (115.9 +/- 23.9 vs 102.7 +/- 25.2 mmol*h/L, p=0.046)
      during an oral glucose tolerance test. In the ADPKD group and among controls no
      association between the investigated polymorphism and secretory function of the
      pancreatic beta-cells or insulin sensitivity was found. CONCLUSION: The C49620T
      ABCC8 polymorphism is associated with anthropometric risk factors for type 2
      diabetes among ADPKD patients, with a protective effect of the TT genotype, but
      without influence on pancreatic beta-cell secretory function or insulin
      sensitivity.

PMID- 22466263
TI  - Renal infarction in patient with long-standing ventricular aneurysm.

PMID- 22466264
TI  - Phosphate binders. Is selection determined by price?: Yes.

PMID- 22466265
TI  - Phosphate binders. Is selection determined by price? No.

PMID- 22466266
TI  - Lupus-related podocytopathy. Could it be a new entity within the spectrum of
      lupus nephritis?

PMID- 22466267
TI  - Cost comparison between haemodialysis and peritoneal dialysis outsourcing
      agreements.

PMID- 22466268
TI  - The importance of addends in cost studies.

PMID- 22466270
TI  - Paricalcitol for pre-dialysis stages of chronic kidney disease.

PMID- 22466272
TI  - Salicylate poisoning.

PMID- 22466273
TI  - Use of estimated glomerular filtration formulas for dose adjustment.

PMID- 22466275
TI  - Endogenous endophthalmitis as a complication of sepsis related to a tunnelled
      haemodialysis catheter.

PMID- 22466276
TI  - Transitory hypernatraemia and hypodipsia in a renal failure patient.

PMID- 22466277
TI  - Renal artery rupture during complicated recovery from angioplasty to treat renal
      stenosis.

PMID- 22466278
TI  - Sub-acute renal failure in patient with fever of unknown origin.

PMID- 22466279
TI  - Pregnancy and haemodialysis: a case study.

PMID- 22466280
TI  - Rhabdomyolysis with acute renal failure secondary to taking methadone.

PMID- 22466281
TI  - Tubulo-interstitial nephritis and uveitis with Fanconi syndrome.

PMID- 22466282
TI  - Self-limiting p-ANCA positive vasculitis in patient with pre-eclampsia.

PMID- 22466283
TI  - Medullary aplasia in c-ANCA positive patient with end-stage lupus nephritis.

PMID- 22466284
TI  - C1q nephropathy and malignancy.

PMID- 22466285
TI  - Prevalence and risk factors for depression and anxiety among outpatient
      migraineurs in mainland China.
AB  - This study aimed to investigate the prevalence and risk factors for anxiety and
      depression symptoms in outpatient migraineurs in mainland China. In addition, we
      evaluated whether the Hospital Anxiety and Depression Scale (HADS) provided
      sufficient validity to screen depression and anxiety. A cross-sectional study was
      conducted consecutively at our headache clinic. Migraine was diagnosed according
      to International Classification of Headache Disorders, 2nd edition (ICHD-II).
      Demographic characteristics and clinical features were collected by headache
      questionnaire. Anxiety and depression symptoms about migraineurs were assessed
      using HADS. Several questionnaires were simultaneously used to evaluate patients
      with depressive disorder including the Hamilton Depression Rating Scale-17
      (HAMD), Hamilton Anxiety Rating Scale (HAMA) and HADS. Pearson correlation
      analysis was applied to test the validity of HADS. 176 outpatients with migraine
      (81.8 % female) were included. Overall, 17.6 and 38.1 % participants had
      depression and anxiety, respectively. Possible risk factors for depression in
      migraineurs included headache intensity of first onset of migraine, migraine with
      presymptom, migraine with family history and migraine disability. The possible
      risk factors for anxiety included fixed attack time of headache in one day and
      poor sleeping, and age represented a protective factor for anxiety. The
      correlation coefficient of HADS-A and HADS-D with HAMA and HAMD was 0.666 and
      0.508, respectively (P < 0.01). This study demonstrates that depression and
      anxiety comorbidity in our mainland Chinese migraineurs are also common, and
      several risk factors were identified that may provide predictive value. These
      findings can help clinicians to identify and treat anxiety and depression in
      order to improve migraine management.

PMID- 22466286
TI  - Sexual selection enables long-term coexistence despite ecological equivalence.
AB  - Empirical data indicate that sexual preferences are critical for maintaining
      species boundaries, yet theoretical work has suggested that, on their own, they
      can have only a minimal role in maintaining biodiversity. This is because long
      term coexistence within overlapping ranges is thought to be unlikely in the
      absence of ecological differentiation. Here we challenge this widely held view by
      generalizing a standard model of sexual selection to include two ubiquitous
      features of populations with sexual selection: spatial variation in local
      carrying capacity, and mate-search costs in females. We show that, when these two
      features are combined, sexual preferences can single-handedly maintain
      coexistence, even when spatial variation in local carrying capacity is so slight
      that it might go unnoticed empirically. This theoretical study demonstrates that
      sexual selection alone can promote the long-term coexistence of ecologically
      equivalent species with overlapping ranges, and it thus provides a novel
      explanation for the maintenance of species diversity.

PMID- 22466287
TI  - Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by
      IL-1beta.
AB  - IL-17-producing CD4+ T helper cells (TH17) have been extensively investigated in
      mouse models of autoimmunity. However, the requirements for differentiation and
      the properties of pathogen-induced human TH17 cells remain poorly defined. Using
      an approach that combines the in vitro priming of naive T cells with the ex vivo
      analysis of memory T cells, we describe here two types of human TH17 cells with
      distinct effector function and differentiation requirements. Candida albicans
      specific TH17 cells produced IL-17 and IFN-gamma, but no IL-10, whereas
      Staphylococcus aureus-specific TH17 cells produced IL-17 and could produce IL-10
      upon restimulation. IL-6, IL-23 and IL-1beta contributed to TH17 differentiation
      induced by both pathogens, but IL-1beta was essential in C. albicans-induced TH17
      differentiation to counteract the inhibitory activity of IL-12 and to prime IL
      17/IFN-gamma double-producing cells. In addition, IL-1beta inhibited IL-10
      production in differentiating and in memory TH17 cells, whereas blockade of IL
      1beta in vivo led to increased IL-10 production by memory TH17 cells. We also
      show that, after restimulation, TH17 cells transiently downregulated IL-17
      production through a mechanism that involved IL-2-induced activation of STAT5 and
      decreased expression of ROR-gammat. Taken together these findings demonstrate
      that by eliciting different cytokines C. albicans and S. aureus prime TH17 cells
      that produce either IFN-gamma or IL-10, and identify IL-1beta and IL-2 as pro-
      and anti-inflammatory regulators of TH17 cells both at priming and in the
      effector phase.

PMID- 22466289
TI  - Low back pain: how does your physical therapist treat low back pain?
AB  - Low back pain is so common that 8 of 10 people experience it at some time in
      their lives. Although the pain in your back may be severe, most low back pain is
      not due to a serious problem. There are many risk factors that increase the
      chances of getting low back pain. As we get older, we often feel more back pain
      due to weakened muscles and stiffening joints. New clinical practice guidelines
      for the treatment of low back pain were published in the April 2012 issue of
      JOSPT. The guidelines describe ways to treat back pain based on best research
      evidence.

PMID- 22466288
TI  - A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.
AB  - The prevalence of obesity and type 2 diabetes is increasing worldwide and
      threatens to shorten lifespan. Impaired insulin action in peripheral tissues is a
      major pathogenic factor. Insulin stimulates glucose uptake in adipose tissue
      through the GLUT4 (also known as SLC2A4) glucose transporter, and alterations in
      adipose tissue GLUT4 expression or function regulate systemic insulin
      sensitivity. Downregulation of human and mouse adipose tissue GLUT4 occurs early
      in diabetes development. Here we report that adipose tissue GLUT4 regulates the
      expression of carbohydrate-responsive-element-binding protein (ChREBP; also known
      as MLXIPL), a transcriptional regulator of lipogenic and glycolytic genes.
      Furthermore, adipose ChREBP is a major determinant of adipose tissue fatty acid
      synthesis and systemic insulin sensitivity. We find a new mechanism for glucose
      regulation of ChREBP: glucose-mediated activation of the canonical ChREBP isoform
      (ChREBP-alpha) induces expression of a novel, potent isoform (ChREBP-beta) that
      is transcribed from an alternative promoter. ChREBP-beta expression in human
      adipose tissue predicts insulin sensitivity, indicating that it may be an
      effective target for treating diabetes.

PMID- 22466290
TI  - The -2518 A/G polymorphism in the monocyte chemoattractant protein 1 gene is
      associated with the risk of developing systemic lupus erythematosus in
      Argentinean patients: a multicenter study.
AB  - Systemic lupus erythematosus (SLE) is a systemic, autoimmune disorder. Monocyte
      chemoattractant protein 1 (MCP-1), a chemokine involved in the recruitment and
      migration of monocytes/macrophages, has been shown to be increased in the plasma
      of SLE patients. The aim of our study was to evaluate the possible association of
      the polymorphism -2518 of the MCP-1 gene with the risk of developing SLE,
      manifesting lupus nephritis (LN) and with other clinical features of SLE in an
      Argentinean population. A group of 171 SLE patients and 120 control subjects were
      examined. Genotypic and allelic frequencies of the MCP-1 -2518 A/G polymorphism
      showed significant differences between the SLE and the control groups (p=0.001
      and p=0.01, respectively). However, the polymorphism showed no association with
      LN or with the other clinical variables studied. Our results suggest that the
      presence of the MCP-1 -2518 A/G polymorphism might be a risk factor for
      developing SLE in genetically predisposed individuals, but it does not seem to
      have a role in the evolution of the disease in the Argentinean population.

PMID- 22466294
TI  - Insights into research on natural products.

PMID- 22466291
TI  - False recognition in a mouse model of Alzheimer's disease: rescue with sensory
      restriction and memantine.
AB  - Alzheimer's disease is commonly regarded as a loss of memory for past events.
      However, patients with Alzheimer's disease seem not only to forget events but
      also to express false confidence in remembering events that have never happened.
      How and why false recognition occurs in such patients is currently unknown, and
      treatments targeting this specific mnemonic abnormality have not been attempted.
      Here, we used a modified object recognition paradigm to show that the tgCRND8
      mouse-which overexpresses amyloid beta and develops amyloid plaques similar to
      those in the brains of patients with Alzheimer's disease-exhibits false
      recognition. Furthermore, we found that false recognition did not occur when
      tgCRND8 mice were kept in a dark, quiet chamber during the delay, paralleling
      previous findings in patients with mild cognitive impairment, which is often
      considered to be prodromal Alzheimer's disease. Additionally, false recognition
      did not occur when mice were treated with the partial N-methyl-d-aspartic acid
      receptor antagonist memantine. In a subsequent experiment, we found abnormally
      enhanced N-methyl-d-aspartic acid receptor-dependent long-term depression in
      these mice, which could be normalized by treatment with memantine. We suggest
      that Alzheimer's disease typical amyloid beta pathology leads to aberrant
      synaptic plasticity, thereby making memory representations more susceptible to
      interfering sensory input, thus increasing the likelihood of false recognition.
      Parallels between these findings and those from the literature on Alzheimer's
      disease and mild cognitive impairment suggest a mechanism underlying false
      recognition in these patients. The false recognition phenomenon may provide a
      novel paradigm for the discovery of potential therapies to treat the mnemonic
      dysfunction characteristic of this disease.

PMID- 22466292
TI  - MicroRNA 486 is a potentially novel target for the treatment of spinal cord
      injury.
AB  - MicroRNAs have been shown to effectively regulate gene expression at the
      translational level. Recently, we identified novel microRNAs that were
      upregulated in a mouse model of spinal cord injury. Among those, we have focused
      on microRNA 486, which directly represses NeuroD6 expression through a conserved
      sequence in its untranslated region. We correlated the overexpression of microRNA
      486 in motor neurons with a poor outcome due to progressive neurodegeneration and
      a pathophysiology that is mediated by reactive oxygen species. The expression of
      microRNA 486 was induced by reactive oxygen species that were produced by
      inflammatory factors, and reactive oxygen species were accumulated in response to
      the knockdown of NeuroD6, which enhances the downregulation of glutathione
      peroxidase 3 and thioredoxin-like 1 after traumatic spinal cord injury. NeuroD6
      directly bound to regulatory regions of thioredoxin-like 1 and glutathione
      peroxidase 3 in motor neurons and activated their expression, which promoted
      reactive oxygen species scavenging. Moreover, knocking down microRNA 486 induced
      the expression of NeuroD6, which effectively ameliorated the spinal cord injury
      and allowed the mice to recover motor function. The infusion of exogenic NeuroD6
      in spinal cord injury lesions effectively blocked apoptosis by reactivating
      thioredoxin-like 1 and glutathione peroxidase 3, which was accompanied by a
      recovery of motor function. Collectively, these findings have identified a novel
      microRNA in spinal cord injury lesions called microRNA 486, demonstrating a new
      role for NeuroD6 in neuroprotection, and suggest a potential therapeutic target
      for spinal cord injuries.

PMID- 22466295
TI  - Prospects for using pre-exposure prophylaxis to control the prevalence of
      HIV/AIDS in China.
AB  - Although important progress has been achieved in combating HIV/AIDs over the past
      30 years, HIV/AIDs is still a serious threat to today's world. In China, figures
      on the incidence of this disease have painted a less than optimistic outlook. As
      the prevailing methods of preventing HIV/AIDS are all partially effective, novel
      and effective preventive interventions are needed in order to control the spread
      of the disease. Pre-exposure prophylaxis (PrEP) is one of the most promising
      prevention strategies and has garnered great attention worldwide. Current
      clinical trials on the efficacy and safety of this strategy have had some
      favorable results though major challenges around the world remain. Thus, China
      has taken an active part in the PrEP study to limit the prevalence of HIV/AIDS.
      This article describes the status of the PrEP study and discusses the
      opportunities and challenges encountered when implementing this strategy in
      China.

PMID- 22466296
TI  - Creatinine and HMH (5-hydroxy-1-methylhydantoin, NZ-419) as intrinsic hydroxyl
      radical scavengers.
AB  - Creatinine (Crn) is one of the main intrinsic hydroxyl radical (*OH) scavengers
      and an ideal one for healthy or normal mammals, although this fact has not yet
      become widely accepted. Our results from urinary data estimated that ca. 0.4-0.6%
      of Crn is used daily to scavenge *OH in normal mammals [ca. 50 MUmole and ca. 400
      pmole of *OH in healthy subjects and normal rats, respectively]. In human
      subjects, Crn reacts non-enzymatically with *OH to form creatol (CTL: 5
      hydroxycreatinine) and demethylcreatinine (DMC) in a one to one ratio, and CTL
      partially decomposes to methylguanidine (MG). And so, the scavenged mole of *OH
      by Crn is nearly equal to their molar total sum (CTL + MG + DMC) or 2 * (CTL +
      MG). The molar ratio of (scavenged *OH)/Crn in healthy subjects and normal rats
      are 4.4 and 6.0 mmole/mole, respectively, i.e. almost similar, but in patients
      with chronic kidney disease (CKD) the ratio increases up to ca. 60 mmole/mole in
      proportion to the severity of CKD. Since the level of Crn might not be enough to
      scavenge all *OH, and MG starts accumulating as a uremic toxin, Crn is not really
      the ideal scavenger. 5-Hydroxy-1-methylhydantoin (HMH, NZ-419), a Crn metabolite,
      is another antioxidant, having *OH scavenging ability, and has been shown to
      inhibit the progression of CKD in rats in stead of Crn, if sufficient amounts are
      given orally.

PMID- 22466297
TI  - GW501516 acts as an efficient PPARalpha activator in the mouse liver.
AB  - The peroxisome proliferator-activated receptor (PPAR) subtype specificity of
      GW501516, a well-known PPARdelta-specific agonist, was studied by examining its
      effects on the expression of endogenous genes in primary hepatocytes and the
      liver of wild-type and PPARalpha-null mice. GW501516, like the PPARalpha-specific
      agonist Wy14,643, induced the expression of several PPAR target genes in a dose
      dependent manner but this action was mostly absent in the cells and liver of
      PPARalpha-null mice. Results indicated that GW501516 acts as an efficient
      PPARalpha activator in the mouse liver.

PMID- 22466298
TI  - Effects of Gosha-jinki-gan (Chinese herbal medicine: Niu-Che-Sen-Qi-Wan) on
      hyperinsulinemia induced in rats fed a sucrose-rich diet.
AB  - We investigated the effects of a Chinese herbal medicine, Gosha-jinki-gan (GJG),
      on the regulation of insulin levels in rats fed a sucrose-rich diet (SRD). Normal
      Wistar rats in the SRD group were fed an SRD for 4 weeks. Increased dietary
      sucrose did not alter plasma glucose levels but it increased plasma insulin
      levels at 2 and 4 weeks in the SRD-fed rats relative to control rats that were
      fed standard chow. GJG treatment significantly suppressed the SRD-induced
      elevation in plasma insulin levels. These results suggest that GJG improves
      hyperinsulinemia caused by an SRD.

PMID- 22466299
TI  - Sedative and anxiolytic effects of the methanolic extract of Leea indica (Burm.
      f.) Merr. leaf.
AB  - The sedative and anxiolytic potential of Leea indica (Burm. f.) Merr., a
      Bangladeshi tribal medicinal plant was studied for the first time. The crude
      methanol extract of L. indica leaves was evaluated for its central nervous system
      (CNS) depressant effect using rodent behavioral models, such as hole cross, open
      field and thiopental sodium induced sleeping time tests for its sedative
      properties and an elevated plus-maze (EPM) test for its anxiolytic potential,
      respectively. The methanol extract of L. indica at doses of 200 mg/kg, p.o. and
      400 mg/kg, p.o., displayed a dose dependent suppression of motor activity,
      exploratory behavior (in hole cross and open field tests) and prolongation of
      thiopental induced sleeping time in mice; the highest CNS depressant effect was
      shown at a dose of 400 mg/kg, p.o. In the EPM test, both dose of methanol extract
      significantly (p < 0.01) increased exploration to and time spent by the treated
      mice in EPM open arms in a dose dependent manner. These results provide in vivo
      evidence that leaves of L. indica in general have significant sedative and
      anxiolytic effects. However, these results may rationalize the scientific basis
      for use of this plant in traditional medicine for treatment of anxiety and
      related disorders.

PMID- 22466300
TI  - Hyaluronic acid in combination with chondroitin sulfate and hyaluronic acid
      improved the degeneration of synovium and cartilage equally in rabbits with
      osteoarthritis.
AB  - The purpose of this study was to compare the chondroprotective effects of
      chondroitin sulfate (CS)-hyaluronic acid (HA) (CS-HA) injection and HA injection
      in an experimental model of osteoarthritis. After induction of osteoarthritis in
      rabbits, 28 rabbits were randomized into four groups: control group, 'HA' group,
      'CS' group, and 'CS-HA' group. After 7 days, rabbits in the control group, 'HA'
      group, 'CS' group and 'CS-HA' group were respectively treated with normal saline,
      HA, CS, or CS-HA injection in the knees. All animals were treated once weekly.
      The animals were treated continuously for 5 weeks. Histological and biochemical
      evaluations were performed. As shown by histological observation, CS-HA injection
      treatment showed a chondroprotective effect on osteoarthritis. However, the
      histological scores of 'HA' group and 'CS-HA' group were not significantly
      different (p > 0.05). The results of biochemical evaluation showed that the
      expression levels of IL-1beta, TNF-alpha, TIMP-1 and NO in synovial fluid of
      treated groups were all different from the control group (p < 0.05). However, the
      expression levels of these biochemical molecules in three treated groups were not
      significantly different (p > 0.05). In conclusion, CS-HA injection showed no
      obvious advantage over HA injection in osteoarthritis treatment.

PMID- 22466301
TI  - Prophylactic effect of Withania somnifera on inflammation in a non-autoimmune
      prone murine model of lupus.
AB  - The immunosuppressive properties of an aqueous suspension of Withania somnifera
      (WS) root powder were investigated in a pristine induced female Balb/c model of a
      systemic lupus erythematosus (SLE) like disease. The course of disease is
      initiated by peritoneal inflammation caused by pristane which results in
      development of SLE like symptoms, i.e. autoantibody production, proteinuria, and
      nephritis within a period of five to six months. The model of SLE was established
      by injecting 0.5 mL of pristane intraperitoneally into female Balb/c mice (12-18
      weeks old). WS root powder (500 mg and 1,000 mg per kg body weight) was
      administered orally from one month prior to disease induction and for the
      following 6 months. Parameters of inflammation like nitric oxide (NO),
      Interleukin 6 and tumour necrosis factor-alpha and reactive oxygen species (ROS)
      in serum and/or ascitic fluid were measured. Prophylactic administration of WS
      root powder (500 mg and 1,000 mg per kg body weight) potently inhibits the
      proinflammatory cytokines, NO, and ROS in the ascetic fluid as well as in serum.
      Therefore, our results indicate a preventive effect of WS root powder on the
      mouse model of lupus.

PMID- 22466302
TI  - Combination of geological data and radon survey results for radon mapping.
AB  - The typical method of radon mapping usually used in most countries is the
      presenting of average radon concentrations in dwellings for districts or regions.
      Sometimes the maps of radon concentrations in the soil or maps of percentage
      above the reference level also demonstrated. Such approach not always can be used
      for identification of the regions with high probability of radon exposure above
      the reference levels where the population density is low. The combination of
      archive geological data and the results of representative radon survey allow
      estimating the typical parameters of radon concentration distribution for
      selected categories of buildings (multi-storey or rural type houses) situated in
      geological zones with the different radon potential. In this case it is possible
      to give grounds for the necessary level of radon protection measures in the new
      buildings constructed in this region. The use of such approach in Ural region of
      Russia is demonstrated.

PMID- 22466303
TI  - Quality assurance for measurements of the radioactivity in the area of the"Horia
      Hulubei" National Institute for Physics and Nuclear Engineering, IFIN-HH.
AB  - This paper presents one part of the activities deployed by the Laboratory for
      Environment and Personnel Dosimetry (LDPM) of IFIN-HH, namely the radiological
      monitoring of the environment within the Institute's area and its surrounding
      influence zone, according to the program approved by the National Regulatory Body
      for Nuclear Activities, CNCAN. The representative reports regard the radioactive
      content of soil, surface and underground water, cultivated and spontaneous
      vegetation, aerosols and atmospheric fallout, sediments. The common requirement
      is that the measured quantities be precise and the reported values be reliable
      and credible. This goal is achieved by maintaining a Quality System, verified
      within the obtaining and maintaining of the laboratory accreditation, according
      to the international standard ISO/IEC 17025:2005.The LDPM is accredited by the
      Romanian accreditation body, RENAR, member of the European Accreditation, EA and
      is designed by CNCAN as a notified testing laboratory. Many measurements were
      performed in collaboration with the Radionuclide Metrology Laboratory (RML) from
      IFIN-HH, RENAR accredited and CNCAN notified for calibration and for testing in
      the field of radioactivity measurement. This paper proposes a short presentation
      of the important aspects in our activity: i. description of equipment,
      samplingmethods, processing and measurement of environmental samples; ii.
      validation of equipment and methods by participation in international and
      national proficiency tests; iii. a five year follow chart, containing the results
      in measurement of samples; iv. a recent application, with a wide impact in
      Romanian mass media: the credible daily report on the possible influence of
      Fukushima accident over the Romanian environmental radioactivity.

PMID- 22466304
TI  - Cost-effective dye-sensitized solar cells consisting of two metal foils instead
      of transparent conductive oxide glass.
AB  - A cost-effective structure for dye-sensitized solar cells (DSSCs) without using
      transparent conductive oxide (TCO) is reported. Instead of high-cost F/SnO(2)
      glass (FTO-glass) or woven metal mesh, a Ti foil and a perforation-patterned
      stainless steel (StSt) foil are introduced as the substrates for a counter
      electrode and a photo-electrode, respectively.

PMID- 22466305
TI  - Central administration of L- and D-aspartate attenuates stress behaviors by
      social isolation and CRF in neonatal chicks.
AB  - Intracerebroventricular (i.c.v.) administration of L-aspartate (L-Asp) attenuates
      stress responses in neonatal chicks, but the mechanism has not been clarified. In
      the present study, three behavioral experiments were carried out under socially
      isolated stressful conditions exacerbated by the use of corticotrophin-releasing
      factor (CRF). In Experiment 1, i.c.v. injection of L-Asp attenuated behavioral
      stress responses (distress vocalization and active wakefulness) in a dose
      dependent manner. Furthermore, L-Asp increased time spent standing/sitting
      motionless with eyes open and sitting motionless with head dropped (sleeping
      posture) in comparison with the group receiving CRF alone. In Experiment 2,
      i.c.v. injection of D-Asp dose-dependently decreased the number of distress
      vocalizations and the amount of time spent in active wakefulness. D-Asp increased
      the time spent standing/sitting motionless with eyes open compared with the group
      receiving CRF alone. In Experiment 3, we directly compared the effect of L-Asp
      with that of D-Asp. Both L- and D-Asp induced sedative effects under an acutely
      stressful condition. However, L-Asp, but not D-Asp, increased the time spent in a
      sleeping posture. These results indicate that both L- and D-Asp, when present in
      the brain, could induce a sedative effect, while the mechanism for hypnosis in
      neonatal chicks may be different for L-Asp in comparison with D-Asp.

PMID- 22466306
TI  - Stunting delays maturation of triceps surae mechanical properties and motor
      performance in prepubertal children.
AB  - Malnutrition can lead to possible irreversible consequences in the development of
      muscle function and some of them are yet poorly characterized. The present study
      evaluated the mechanical properties of the triceps surae and motor performance in
      stunted (S) and eutrophic (E) prepubertal children (9 years +/- 6 months). Height
      for-age ratio was used as indicator of stunting due to early malnutrition,
      according to the World Health Organization. Torque was determined by maximal
      voluntary contractions (MVC) and musculotendinous (MT) stiffness was achieved
      through quick-release tests to obtain MT stiffness index (SI(MT)) and passive
      stiffness (K (p)) from linear MT stiffness-torque relationships. Percutaneous
      supramaximal electrically elicited contractions determined twitch torque (Pt) and
      electromechanical delay (EMD). Motor performance was evaluated by balance test. S
      group presented significantly lower MVC and a trend of lower Pt values indicating
      lower capacities to develop force under voluntary or induced conditions.
      Significantly higher SI(MT) and EMD values were observed, while K (p) and motor
      performance in balance were significantly lower. Higher SI(MT) values have been
      reported previously in youngest prepubertal children, indicating that immature
      activation capacities can mask MT stiffness assessment during voluntary
      contractions, taking into consideration the higher EMD values as a measure of
      muscle stiffness contribution. Lower K (p) may indicate a delay in the maturation
      of tendinous tissue in S group, influencing motor performance in balance. The
      present study shows that malnutrition leads to adaptation of intrinsic MT elastic
      properties, but depends on the level of the observed structure.

PMID- 22466307
TI  - Urine citrate and 6-sulfatoximelatonin excretion during a training season in top
      kayakers.
AB  - The effects of high training loads during the competitive kayaking season may be
      reflected in urinary citrate and 6-sulfatoxymelatonin ((alpha)MT6S) excretion.
      The present study aims to evaluate the influence of a training program on citrate
      and (alpha)MT6S excretion in 12 elite kayakers. Urine samples were collected
      (before bedtime and again in the morning, at first voiding) at the beginning of
      the season (second half of October), during the macrocycle (specific training
      period; first week of June), and tapering (precompetitive training period; first
      week of July) stages. During the training season, urine citrate values (mg/L)
      were higher in the evening than in the morning in all stages (p < 0.01). The data
      obtained in the evening showed the lowest significant values (p < 0.05) in the
      beginning stage compared with the macrocycle and tapering stages. The values
      obtained in the morning showed the lowest significance (p < 0.05) in the
      macrocycle stage compared to the beginning and the tapering stages. In all
      stages, (alpha)MT6S (ng/mL) evening values were significantly lower (p < 0.05)
      than the morning values. The morning/evening ratio, total sum, and nocturnal
      increment of (alpha)MT6S did not vary across the training stages. From these
      results, it can be deduced that the pineal function is unaltered and that citrate
      turnover is good in elite kayakers during the training season. It was found that
      urine citrate and (alpha)MT6S obtained by non-invasive techniques may be used as
      major markers to evaluate metabolic recovery and stress produced by the training
      season workload in elite kayakers.

PMID- 22466308
TI  - Hypoxia, a multifaceted phenomenon: the example of the "normobaric oxygen
      paradox".

PMID- 22466309
TI  - Age-related fascicle-tendon interaction in repetitive hopping.
AB  - Increasing age can influence the interaction of muscle fascicles and tendon
      during dynamic movements. The object of the present study was to examine
      occurrence and possible reasons for the age-specific behavior of fascicles and
      tendons and their interaction during hopping with different intensities. Nine
      young and 24 elderly subjects performed repetitive hopping with maximal effort as
      well as with 50, 65, 75 and 90 % intensities. During hopping joint kinematics and
      ground reaction, forces were measured together with recordings of ultrasound
      images of both the fascicle and the muscle-tendon junction part of the
      gastrocnemius medialis (GaM) muscle. The results showed that fascicle behavior
      during the braking phase of hopping was clearly age specific in nature with more
      fascicle shortening in the young (p < 0.001). In addition, the fascicle
      shortening increased in young subjects with increasing intensity (p < 0.05). At
      the instant of ground contact, the elderly subjects demonstrated decreased
      fascicle length with increasing hopping intensity (p < 0.01). Thereafter in the
      braking phase, the elderly showed much smaller changes in fascicle length as
      compared to the young. In contrast to the fascicles, the GaM outer tendon did not
      show major age-specific differences in stretching and shortening amplitudes
      during hopping although the peak tendon forces were clearly lower in the elderly
      (p < 0.001). These results suggest that GaM outer tendon behavior is not
      influenced greatly with increasing age. It is further suggested that when aging
      modifies the fascicle-tendon interaction, it is primarily due to the age-specific
      difference in the fascicle level. This notion poses a question that as compared
      to the young, the elderly individuals may have a different fascicle behavior for
      optimal SSC locomotion such as hopping.

PMID- 22466310
TI  - Prevailing evidence contradicts the notion of a "normobaric oxygen paradox".

PMID- 22466311
TI  - Effect of feeding on the function and structure of the digestive system in
      juvenile southern catfish (Silurus meridionalis Chen).
AB  - Postprandial physiological and morphological responses to feeding were examined
      in juvenile southern catfish (Silurus meridionalis Chen) that had consumed a
      loach (Misgurnus anguillicaudatus Cantor) meal equivalent to 6 % of the body mass
      of the catfish. The gastric evacuation rate (GER) peaked at 4 h postfeeding,
      averaging 0.36 g food weight h(-1), at which time 14 % of the ingested meal had
      passed into the intestine. Less than 10 % of the ingested meal remained in the
      stomach at 24 h postfeeding. Pepsin activity peaked at 8 h postfeeding, reaching
      a level approximately twofold higher than the prefeeding level. Pancreatic
      trypsin activity peaked at 16 h postfeeding, reaching a level 4.5-fold higher
      than the prefeeding level. Peaks in lipase activity in both the proximal and
      middle intestinal segments occurred at 16 h, reaching 2.8- and 2.4-fold higher
      levels than the prefeeding level, respectively, while the activity in the distal
      intestine segment reached a level 2.9-fold higher than the prefeeding level at 24
      h postfeeding. With respect to amylase activity, only the middle intestinal
      segment exhibited a change, first an increase and then a decrease, after feeding.
      Feeding also triggered an approximately 200 % increase in the metabolic rate and
      resulted in 44.6 kJ kg(-1) being expended on specific dynamic action, equivalent
      to 16.1 % of the meal's energy. In terms of organ size, the wet mass of the liver
      increased by 11 % at 24 h postfeeding, whereas the wet mass of the pancreas did
      not change. Except for a decrease in the thickness of the submucosa in the middle
      intestinal segment, the thickness of the intestinal fold, mucosa, submucosa,
      muscularis and serosa of each intestinal segment did not change significantly
      with feeding. These results suggest that the continuum of physiological responses
      observed with respect to metabolic increases, GER, regulation of pancreatic and
      intestinal digestive enzyme activities and liver wet mass to feeding corresponds
      to the changes in the demand on the digestive system in S. meridionalis.
      Moreover, species maintained stable gastrointestinal tract morphology during the
      short interval of repeated feeding.

PMID- 22466312
TI  - Preventive health services delivery to South Asians in the United States.
AB  - There is limited information on the health status of South Asians. Our objective
      was to examine the delivery of clinical preventive services to South Asian
      adults. We used data from a 2001 mail survey to a nationwide sample of South
      Asians. We quantified the percentage of eligible adults who received screenings
      for colorectal cancer, cervical cancer, breast cancer, high blood pressure, lipid
      disorders, and vaccinations against influenza, pneumococcus, and tetanus. We also
      calculated the number of individuals who were up-to-date with all their
      recommended preventive healthcare. One-fourth of South Asians were up-to-date
      with their recommended preventive services, while more than half were not up-to
      date with their services. Having a regular source of care was significantly
      associated with being up-to-date on recommended schedules. Despite their high
      level of education, the majority of South Asians in the US are not receiving the
      appropriate amount of preventive health services.

PMID- 22466313
TI  - Phosphorus containing mixed anhydrides--their preparation, labile behaviour and
      potential routes to their stabilisation.
AB  - Simple mixed anhydrides are known to pose synthetic difficulties relating to
      their thermal lability and ways to stabilise such mixed anhydride systems by
      relying on either electronic or steric effects were therefore explored. Thus, a
      series of acyloxyphosphines and acylphosphites derived from either propanoic acid
      or phenylacetic acid were prepared and their in solution stability assessed.
      These compounds were, where stability allowed, fully characterised using standard
      analytical techniques. NMR studies, in particular, unearthed interesting coupling
      behaviour for a number of the acyloxyphosphines and acylphosphites as well as
      their rearrangement products which could be linked to their chiral nature.
      Furthermore, the crystal structures for three of the prepared mixed anhydrides
      were determined using X-ray crystallography and are reported herein.

PMID- 22466314
TI  - Electron transport properties of single molecular junctions under mechanical
      modulations.
AB  - Electron transport behaviors of single molecular junctions are very sensitive to
      the atomic scale molecule-metal electrode contact interfaces, which have been
      difficult to control. We used a modified scanning probe microscope-break junction
      technique (SPM-BJT) to control the dynamics of the contacts and simultaneously
      monitor both the conductance and force. First, by fitting the measured data into
      a modified multiple tunneling barrier model, the static contact resistances,
      corresponding to the different contact conformations of single alkanedithiol and
      alkanediamine molecular junctions, were identified. Second, the changes of
      contact decay constant were measured under mechanical extensions of the molecular
      junctions, which helped to classify the different single molecular conductance
      sets into specific microscopic conformations of the molecule-electrode contacts.
      Third, by monitoring the changes of force and contact decay constant with the
      mechanical extensions, the changes of conductance were found to be caused by the
      changes of contact bond length and by the atomic reorganizations near the contact
      bond. This study provides a new insight into the understanding of the influences
      of contact conformations, especially the effect of changes of dynamic contact
      conformation on electron transport through single molecular junctions.

PMID- 22466316
TI  - GH and IGF1: roles in energy metabolism of long-living GH mutant mice.
AB  - Of the multiple theories to explain exceptional longevity, the most robust of
      these has centered on the reduction of three anabolic protein hormones, growth
      hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50%
      longer and exhibit significant differences in several aspects of energy
      metabolism as compared with wild-type mice. Mitochondrial metabolism is
      upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice
      treated with GH, multiple aspects of these pathways are suppressed. Core body
      temperature is markedly lower in dwarf mice, yet whole-body metabolism, as
      measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/-
      mice compared with normal controls. Elevated adiponectin, a key antiinflammatory
      cytokine, is also very likely to contribute to longevity in these mice. Thus,
      several important components related to energy metabolism are altered in GH
      mutant mice, and these differences are likely critical in aging processes and
      life-span extension.

PMID- 22466317
TI  - Diverging antioxidative responses to IGF-1 in cultured human skin fibroblasts
      versus vascular endothelial cells.
AB  - Insulin-like growth factor 1 (IGF-1) stimulates cell proliferation and is crucial
      for maintenance of somatic tissues. However, this effect is associated with the
      inhibition of FOXO transcription factors and downregulation of antioxidative
      enzymes. In this study, we compared the responses of primary dermal fibroblasts
      and human umbilical vein endothelial cells with IGF-1 treatment. We found that
      IGF-1 primarily downregulated enzymatic antioxidants in skin fibroblasts.
      However, human umbilical vein endothelial cells were protected from an IGF-1
      mediated decrease in antioxidative capacity. Moreover, IGF-1 also activated
      endothelial nitric oxide synthase in human umbilical vein endothelial cells.
      These observations suggest a dichotomous role for IGF-1, which provides for
      growth and repair needs of the soma, while attenuating the effect of oxidative
      stress on the vasculature by activating endothelial nitric oxide synthase. This
      increases the production of nitric oxide, an antiproliferative and, under certain
      circumstances, an antioxidant agent. Findings could help clarify the role of IGF
      1 in aging and longevity of lower organisms, short-lived mammals, and humans.

PMID- 22466318
TI  - Reliability of the diagnostic tests for Cushing's syndrome performed in a
      tertiary referral center.
AB  - The study aimed to retrospectively evaluate the reliability of the diagnostic and
      location tests in Cushing's Syndrome (CS). Eighty-seven patients diagnosed with
      CS between 1995 and 2007 by Endocrinology Metabolism Department of Cerrahpasa
      Medical School were included in the study. The control group consisted of 91
      patients who presented to the outpatient clinic because of obesity. The
      diagnostic tests were as follows: 1 mg dexamethasone suppression test (DST), 24-h
      urinary free cortisol (UFC), midnight cortisol level (MCL), ACTH level and
      overnight 8 mg DST. The sensitivity and specificity of UFC were 81 and 66 %
      respectively for the cut-off point of 50 MUg/day, whereas they were 64 and 76 %
      respectively for the cut-off point of 100 MUg/day. For the cut-off value of
      1.8/MUg/dL for MCL and 1 mDST, the sensitivity rates were 100 and 98 %, while the
      specificity rates were 88 and 33 %, respectively. Among the location tests, the
      sensitivity and specificity of ACTH under 10 pg/mL for adrenal CS were 92 and 94
      % respectively. The sensitivity and specificity of ACTH higher than 30 pg/mL for
      ACTH-dependent CS were 69 and 100 % respectively. The sensitivity rates of 8 mg
      DST for 50 and 60 % suppressions were 83 and 79 % respectively, whereas the
      specificity rates were 75 and 88 % respectively. 1 mg DST (cut-off <1.8 MUg/dL)
      and UFC (50 MUg/24 h) are appropriate tests for screening CS. Overnight 8 mg DST
      with 60 % suppression for Cushing's Disease (CD) and ACTH levels <10 pg/mL for
      adrenal CS, ACTH levels >30 pg/mL for ACTH dependency were identified as the best
      tests for the differential diagnosis of the subtypes.

PMID- 22466319
TI  - Early-onset infections of very-low-birth-weight infants in Polish neonatal
      intensive care units.
AB  - AIM: The objective of this study was to investigate the incidence, causes, the
      risk factors, etiologic agents and the outcomes of early-onset infections (EOIs)
      in very-low-birth-weight newborns in Polish neonatal intensive care units.
      METHODS: Continuous prospective infection surveillance conducted during 2009 at 6
      Polish neonatal intensive care units and included 910 newborns whose birth weight
      was lower than 1500 g. Infections were defined according to the Gastmeier's
      criteria. EOIs were diagnosed <3 days after delivery. RESULTS: The frequency of
      early-onset septicemia (EOS) was 7.0% and of early-onset pneumonia (EO-pneumonia)
      8.6%. The factors significantly increasing the risk of EOS were low gestational
      age, small birth weight, low score in the Clinical Risk Index for Babies and
      Apgar score as well as maternal chorioamnionitis. The perinatal prophylaxis did
      not have an influence on the occurrence of EOS. The factors considerably
      increasing the risk of EO-pneumonia were low scores in the Clinical Risk Index
      for Babies and Apgar scores, a low gestational age and bacterial vaginosis in the
      child's mother during pregnancy. The most important etiologic organisms were Gram
      positive cocci (39.7% of all the infections, 47.8% in EOS), Streptococcus
      agalactiae (20% of the EOS), Gram-negative bacilli (33.3% isolates), yeast-like
      fungi (isolated in 7.9% of cases) and atypical bacteria (22% of the cases of EO
      pneumonia). CONCLUSIONS: The observed frequency of EOS did not differ from the
      one described in the literature, whereas the frequency of EO-pneumonia was
      higher. The bacterial etiologies suggest the vertical transmission of the
      pathogens and a close relationship between the observed EOIs with maternal
      environment. The applied perinatal antibiotic prophylaxis was ineffective.

PMID- 22466320
TI  - Discordant drug susceptibility for mycobacterium tuberculosis within families.
AB  - Children with presumed tuberculosis who are in contact with a multidrug-resistant
      source case should be treated according to the drug susceptibility of the source
      case's isolate. However, it is important to obtain a microbiologic diagnosis as
      it is possible for the child to have a different susceptibility profile to the
      source case. We present 2 such cases.

PMID- 22466321
TI  - Correlates for second-dose varicella vaccination in school-age children in a
      managed care organization in California.
AB  - OBJECTIVE: To identify correlates of nonadherence to the recommendation for
      routine second-dose varicella vaccination in a diverse sample of school-age
      children. METHODS: A total of 67,977 children of 4-6 years (51% male, 50%
      Hispanic) were included in this retrospective cohort study. The second-dose
      varicella vaccination history was evaluated by using the Kaiser Immunization
      Tracking System. Correlation and multivariable regression analyses were used to
      test the association between potential correlates and nonadherence to the second
      dose varicella vaccination. RESULTS: Four-year-old children had a significantly
      higher vaccination rate (76.1%) than 5-year-olds (43.2%) and 6-year-olds (17.3%)
      by 12 months after the implementation of routine second-dose varicella
      vaccination. Non-Hispanic white race [rate ratio (RR): 1.13 (95% CI: 1.11-1.15)],
      living in an area of >75% adults with a high-school diploma [RR: 1.17 (95% CI:
      1.14-1.20)], and having a primary care provider specializing in family medicine
      [RR: 1.15 (95% CI: 1.11-1.18)] significantly correlated with nonadherence. Missed
      opportunity was found in 59.7% (n=20,465) of children who did not receive the
      second-dose varicella vaccine in spite of at least 1 outpatient visit and in
      15.8% (n=5407) who received some other vaccines during the follow-up period.
      CONCLUSIONS: Efforts targeting non-Hispanic white and black children, parents
      with a high education level and family medicine physicians might improve uptake
      of the routine 2-dose varicella vaccination. Incorporation of a requirement for
      the second-dose varicella vaccine into the school law might help achieve high
      adherence to the routine 2-dose varicella vaccination in school-age children.

PMID- 22466322
TI  - Immunogenicity and safety of a quadrivalent live attenuated influenza vaccine in
      children.
AB  - BACKGROUND: Influenza B viruses from 2 lineages cocirculate annually. Because the
      single B strain contained in trivalent vaccines may not match the major
      circulating strain, adding a second B virus could enhance protection. This study
      compared the safety and immunogenicity of an investigational quadrivalent Ann
      Arbor strain live attenuated influenza vaccine (Q/LAIV) with that of 2 trivalent
      vaccines (T/LAIV), each containing a B strain from a different lineage. METHODS:
      This randomized, double-blind study was designed to demonstrate the immunologic
      noninferiority of Q/LAIV compared with T/LAIV in children 2-17 years of age by
      comparing postdose geometric mean titers of hemagglutination inhibition
      antibodies. Children were randomized 3:1:1 to receive Q/LAIV or 1 of 2 T/LAIV
      vaccines. Those subjects who were 9-17 years of age received 1 dose, and those 2
      8 years of age received 2 doses 1 month apart. Serum immune responses were
      evaluated 1 month after dose 1 (dose 2 for influenza vaccine-naive subjects aged
      2-8 years). RESULTS: Q/LAIV was noninferior to T/LAIV: upper bounds for all four
      95% confidence intervals for the postdose geometric mean titer ratios (T/LAIV
      divided by Q/LAIV) were <=1.5, the predefined noninferiority margin. The overall
      seroresponse rates (4-fold rise) were comparable between treatment groups. Safety
      events were comparable, except that fever was more common after dose 1 in Q/LAIV
      subjects (5.1%) than in T/LAIV subjects (3.1%) 2-8 years of age. CONCLUSIONS: The
      immunogenicity of Q/LAIV was noninferior to that of T/LAIV in children aged 2-17
      years; safety was also comparable. Q/LAIV may broaden the protection against
      influenza B strains provided by current trivalent influenza vaccines.

PMID- 22466323
TI  - Case characteristics and use of oseltamivir in children and household contacts.
AB  - In May 2009, the onset of pandemic influenza A (H1N1) began in Buenos Aires
      schools and a containment program was implemented. We report the first 191 school
      aged cases. Influenza (H1N1) was a mild disease in children. Oseltamivir was well
      tolerated and resulted in a significantly reduced duration of symptoms in this
      group. Oseltamivir was also effective at preventing secondary cases.

PMID- 22466324
TI  - Investigation and control of an outbreak of imipenem-resistant Acinetobacter
      baumannii Infection in a Pediatric Intensive Care Unit.
AB  - BACKGROUND: This study investigated the clinical details and epidemiology of the
      imipenem-resistant Acinetobacter baumannii (IRAB) outbreak that occurred at a
      pediatric intensive care unit (PICU), and describes successful outcome of the
      implemented infection control measures. METHODS: With the recognition of 3
      clustered cases with IRAB bacteremia at the PICU of Seoul National University
      Children's Hospital, Korea, from August to September 2010, the following outbreak
      control strategies were implemented: reinforcement of hand hygiene and contact
      precautions, investigation of environmental contamination, disinfection of the
      contaminated environment and medical equipment, active surveillance culture upon
      PICU admission and isolation of IRAB-positive patients. The clinical and
      microbiological data were reviewed for A. baumannii positive cases in the PICU
      from April 2001 to June 2011. Multilocus sequence typing was also performed.
      RESULTS: Twenty IRAB-positive cases (bacteremia in 10, pneumonia in 3 and
      colonizers in 7) were detected from January 2010 to February 2011. Thirteen IRAB
      infected patients were all placed on a mechanical ventilator, had central venous
      catheters, received broad-spectrum antimicrobial treatment and had underlying
      diseases. Eleven (85%) IRAB-infected patients died probably due to IRAB
      infection. IRAB grew in 4 samples obtained from sinks and water taps from 38
      environmental samples. Multilocus sequence typing analysis revealed 2 sequence
      types: ST138 (n=16) and its single-locus variant ST92 (n=4). Eleven weeks after
      the initiation of active surveillance, no further IRAB isolates were identified.
      CONCLUSIONS: This study identifies the environmental source of an IRAB outbreak
      in a PICU and describes successful control of the outbreak with a multicomponent
      intervention program.

PMID- 22466325
TI  - Bloodstream infections during the first year after pediatric small bowel
      transplantation.
AB  - BACKGROUND: Little information regarding bloodstream infections (BSIs) in small
      bowel transplantation has been published. METHODS: We reviewed the medical
      records of 98 pediatric patients who underwent small bowel transplantation.
      Patients' characteristics were analyzed with Wilcoxon rank-sum, chi or Fisher's
      exact tests. We estimated the overall survival by the Kaplan-Meier method and
      compared survival distributions between groups with the log-rank test. RESULTS:
      Sixty-eight patients developed >=1episode of BSIs (total of 146 episodes), and
      69.1% of the first infections were diagnosed in the 3 months post
      transplantation. The most common sources of infection were as follows: central
      venous catheters (49.3%) and intra-abdominal infections (32.9%). Central venous
      catheters were present in 86.3%, and total parenteral nutrition within 7 days
      before infection was administered in 72.6% of episodes. Gram-positive bacteria
      (96 isolates) were more frequently isolated than Gram-negative bacteria (52
      isolates), with Enterococcus spp. being the most commonly identified (48
      isolates), followed by coagulase-negative Staphylococcus (40 isolates). Patients
      with infections were younger than those without (median 1.4 versus 2.1 years,
      P=0.02). Four grafts were lost after transplantation in patients with BSIs and 2
      in patients without BSIs (P = 0.99). One-year survival rate for patients without
      BSIs was 86.7% (95% confidence interval: 68.3%-94.8%) versus 72.1% in patients
      with BSIs (95% confidence interval: 59.8%-81.2%). Overall time to death was
      shorter in patients with BSIs than in patients without BSIs (P=0.056).
      CONCLUSIONS: Almost 70% of small bowel transplantation recipients developed BSIs,
      mainly in the early months after transplantation. BSIs were mainly from a central
      venous catheter or intra-abdominal source. Enterococcus spp were the most
      frequently isolated organisms. Patients with BSIs had worse survival than
      patients with BSIs.

PMID- 22466326
TI  - Antibiotic therapy for pediatric community-acquired pneumonia: do we know when,
      what and for how long to treat?
AB  - Community-acquired pneumonia (CAP) is a common cause of morbidity among children
      in developed countries and accounts for an incidence of 10-40 cases per 1000
      children in the first 5 years of life. Given the clinical, social and economic
      importance of CAP, there is general agreement that prompt and adequate therapy is
      essential to reduce the impact of the disease. The aim of this discussion paper
      is to consider critically the available data concerning the treatment of
      uncomplicated pediatric CAP and to consider when, how and for how long it should
      be treated. This review has identified the various reasons that make it difficult
      to establish a rational approach to the treatment of pediatric CAP, including the
      definition of CAP, the absence of a pediatric CAP severity score, the difficulty
      of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD)
      studies, the high resistance of the most frequent respiratory pathogens to the
      most widely used anti-infectious agents and the lack of information concerning
      the changes in CAP epidemiology following the introduction of new vaccines
      against respiratory pathogens. More research is clearly required in various
      areas, such as the etiology of CAP and the reasons for its complications, the
      better definition of first- and second-line antibiotic therapies (including the
      doses and duration of parenteral and oral antibiotic treatment), the role of
      antiviral treatment and on how to follow-up patients with CAP. Finally, further
      efforts are needed to increase vaccination coverage against respiratory pathogens
      and to conduct prospective studies of their impact.

PMID- 22466327
TI  - Tympanostomy with and without adenoidectomy for the prevention of recurrences of
      acute otitis media: a randomized controlled trial.
AB  - BACKGROUND: The prevention of otitis media, particularly among infants, remains a
      controversial issue. We evaluated the efficacy of insertion of tympanostomy tubes
      with and without adenoidectomy for preventing recurrent acute otitis media (AOM)
      in young children. METHODS: We randomly assigned 300 children aged 10 months to 2
      years who had recurrent AOM to groups receiving tympanostomy tubes (Tymp) (n =
      100), tympanostomy tubes with adenoidectomy (TympAde) (n = 100) or neither
      (Contr) (n = 100). All the children were followed up for 12 months. RESULTS: The
      primary outcome was intervention failure (2 AOM episodes in 2 months, 3 in 6
      months or persistent effusion lasting for 2 months). Intervention failed in 21%
      of cases (21/100) in the Tymp group, 16% (16/100) in the TympAde group and 34%
      (34/100) in the Contr group. The absolute differences were -13% [95% confidence
      interval (CI) -25% to -1%, P = 0.04] between the Tymp and Contr groups and -18%
      (95% CI -30 to -6%, P =0.004) between the TympAde and Contr groups. CONCLUSIONS:
      Insertion of tympanostomy tubes alone or with adenoidectomy was effective in
      preventing recurrent AOM episodes in children younger than 2 years of age.

PMID- 22466328
TI  - T-cell responses in children to internal influenza antigens, 1 year after
      immunization with pandemic H1N1 influenza vaccine, and response to revaccination
      with seasonal trivalent-inactivated influenza vaccine.
AB  - BACKGROUND: During seasonal influenza epidemics, 5-15% of the population are
      affected with an illness having a nontrivial mortality, morbidity and economic
      burden. Inactivated influenza vaccines are routinely used to prevent influenza
      infection, primarily by inducing humoral immunity. In addition, trivalent
      inactivated influenza vaccines have previously been shown to boost influenza
      specific T-cell responses in a small percentage of adults. We investigate here
      the influenza-specific T-cell response, in children, 1 year after pandemic H1N1
      vaccination and the ability to boost the T-cell response with trivalent
      inactivated influenza immunization. METHODS: Peripheral blood mononuclear cells
      (PBMCs) were isolated from children previously vaccinated with pandemic H1N1
      vaccine, pre- and postseasonal 2010-2011 trivalent influenza vaccine (TIV)
      vaccination. Samples were analyzed by interferon-gamma enzyme-linked
      immunosorbent spot for reactogenicity toward internal influenza antigens
      (nucleoprotein, matrix protein 1 and nonstructural protein 1). RESULTS: Basal ex
      vivo T-cell responses to nucleoprotein, matrix protein 1 and nonstructural
      protein 1 measured by interferon-gamma enzyme-linked immunosorbent spot assay
      were significantly higher in those children who had previously received an AS03B
      adjuvanted split virion pandemic vaccine 12 months earlier rather than a
      nonadjuvanted whole virion vaccine. Boosting of these responses, 21 days after
      2010/2011 seasonal TIV vaccination was observed regardless of age or prior
      pandemic vaccination regime, although boosting was greater in those groups with
      the lowest initial response. CONCLUSIONS: We show here that children previously
      vaccinated with the 2009 pandemic H1N1 vaccine have measurable T-cell responses 1
      year after vaccination. The magnitudes of these responses are dependent on both
      age of vaccine and type of pandemic H1N1 vaccine used. After 2010/2011 seasonal
      TIV vaccination, these T-cell responses undergo a small but significant boost.

PMID- 22466329
TI  - Efficacy and safety of long-term adefovir dipivoxil therapy in children with
      chronic hepatitis B infection.
AB  - BACKGROUND: The safety and efficacy of adefovir dipivoxil (ADV) for chronic
      hepatitis B infection in children was demonstrated in a randomized, placebo
      controlled trial. Those children were followed for 4 more years, and many
      continued to receive ADV for all or part of this time. OBJECTIVES: To examine the
      therapeutic effects and safety of prolonged ADV therapy in children with chronic
      hepatitis B infection. METHODS: After 48 weeks of double-blind treatment, all
      placebo-treated subjects who did not exhibit HBeAg seroconversion at week 44, and
      all ADV-treated subjects, were offered open-label ADV for up to 192 additional
      weeks. Treatment was discontinued if there was no virologic effect, except for
      adolescents with previous lamivudine exposure, in whom lamivudine was added to
      ADV. Durability of HBeAg seroconversion was assessed. Annual resistance
      surveillance was conducted in subjects who had detectable hepatitis B virus DNA.
      RESULTS: Of the 170 subjects who completed the 48-week study, 162 participated in
      the open-label study. ADV was discontinued in 61 subjects due to virologic
      failure. In subjects who continued treatment, either as monotherapy or with
      lamivudine, continued viral suppression and alanine aminotransferase
      normalization were noted. HBeAg seroconversions were observed in 55 subjects, and
      hepatitis B surface antigen seroconversion in 5. Mean duration of HBeAg
      seroconversion at last observation was 762 +/- 371.2 days in the ADV-ADV group
      and 643 +/- 291.5 days in the PLB-ADV group. ADV was safe and well-tolerated.
      Resistance to ADV was observed in 1 child on ADV monotherapy. Nine treatment
      experienced subjects entered the study with mutations associated with lamivudine
      resistance. All responded to ADV therapy. CONCLUSIONS: Prolonged ADV treatment is
      safe in children. If reserved only for those with virologic response within 6
      months, viral resistance was minimal.

PMID- 22466330
TI  - Acute appendicitis associated with scarlet fever.

PMID- 22466331
TI  - Novel immunotherapy for malignant melanoma with a monoclonal antibody that blocks
      CEACAM1 homophilic interactions.
AB  - CEACAM1 (biliary glycoprotein-1, CD66a) was reported as a strong clinical
      predictor of poor prognosis in melanoma. We have previously identified CEACAM1 as
      a tumor escape mechanism from cytotoxic lymphocytes. Here, we present substantial
      evidence in vitro and in vivo that blocking of CEACAM1 function with a novel
      monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy.
      MRG1, a murine IgG1 monoclonal antibody, was raised against human CEACAM1. It
      recognizes the CEACAM1-specific N-domain with high affinity (K(D) ~ 2 nmol/L).
      Furthermore, MRG1 is a potent inhibitor of CEACAM1 homophilic binding and does
      not induce any agonistic effect. We show using cytotoxicity assays that MRG1
      renders multiple melanoma cell lines more vulnerable to T cells in a dose
      dependent manner, only following antigen-restricted recognition. Accordingly,
      MRG1 significantly enhances the antitumor effect of adoptively transferred,
      melanoma-reactive human lymphocytes using human melanoma xenograft models in
      severe combined immunodeficient/nonobese diabetic (SCID/NOD) mice. A significant
      antibody-dependent cell cytotoxicity response was excluded. It is shown that MRG1
      reaches the tumor and is cleared within a week. Importantly, approximately 90% of
      melanoma specimens are CEACAM1(+), implying that the majority of patients with
      melanoma could be amenable to MRG1-based therapy. Normal human tissue microarray
      displays limited binding to luminal epithelial cells on some secretory ducts,
      which was weaker than the broad normal cell binding of other anticancer
      antibodies in clinical use. Importantly, MRG1 does not directly affect CEACAM1(+)
      cells. CEACAM1 blockade is different from other immunomodulatory approaches, as
      MRG1 targets inhibitory interactions between tumor cells and late effector
      lymphocytes, which is thus a more specific and compartmentalized immune
      stimulation with potentially superior safety profile.

PMID- 22466332
TI  - Functional imaging in hyperinsulinemic hypoglycemia after gastric bypass surgery
      for morbid obesity.
AB  - CONTEXT: Hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass (RYGB) has
      been increasingly reported. It is induced by beta-cell hyperplasia often referred
      to as nesidioblastosis. Positron emission tomography (PET) with [11C]-5
      hydroxytryptophan ((11)C-HTP) and 6-[18F]fluoro-3,4-dihydroxy-l-phenylalanine
      ((18)F-DOPA) has been successfully applied to image neuroendocrine tumors. No
      data are available of the usefulness of these functional imaging techniques in
      post-RYGB in this new endocrine disorder, neither for diagnostic purposes nor for
      follow-up. OBJECTIVE: We present a patient with post-RYGB hypoglycemia who
      underwent (11)C-HTP and (18)F-DOPA PET scintigraphy for diagnostic purposes and
      to evaluate the effect of additional laparoscopic adjustable banding of the pouch
      as a surgical therapy for this disorder. PATIENT: We describe a woman with
      biochemically confirmed post-RYGB hypoglycemia who showed diffuse uptake of the
      (11)C-HTP and (18)F-DOPA tracers in the entire pancreas. After failure of dietary
      and medical treatment options, she underwent a laparoscopic adjustable banding
      for pouch dilatation. Subjective improvement was noted, which coincided with
      decreased uptake of (18)F-DOPA and (11)C-HTP in the head of the pancreas.
      CONCLUSIONS: Functional imaging by (18)F-DOPA- and (11)C-HTP-PET can accurately
      visualize diffuse endocrine pancreatic activity in post-gastric bypass
      hyperinsulinemic hypoglycemia. Both (11)C-HTP- and (18)F-DOPA-PET imaging appear
      to have a similar diagnostic performance in the presented case, and uptake of
      both tracers potentially relates to disease activity after surgical intervention.

PMID- 22466333
TI  - Prenatal dexamethasone treatment of children at risk for congenital adrenal
      hyperplasia: the Swedish experience and standpoint.

PMID- 22466334
TI  - PROKR2 variants in multiple hypopituitarism with pituitary stalk interruption.
AB  - CONTEXT: Pituitary stalk interruption represents a frequent feature of congenital
      hypopituitarism, but only rare cases have been assigned to a known genetic cause.
      OBJECTIVE: Using a candidate gene approach, we tested several genes as potential
      causes of hypopituitarism with pituitary stalk interruption. We hypothesized that
      ectopic posterior pituitary may be a consequence of defective neuronal axon
      projections along the pituitary stalk or defective angiogenesis of hypophyseal
      portal circulation. Considering the role of the prokineticin 2 pathway in
      angiogenesis and neuronal migration, we screened PROK2 and PROKR2 genes. DESIGN:
      PROK2 and PROKR2 and all genes previously known to be involved in hypopituitarism
      with pituitary stalk interruption (LHX4, HESX1, OTX2, and SOX3) were screened in
      72 index cases with pituitary stalk interruption syndrome from the GENHYPOPIT
      database. In vitro studies were performed to assess the functional consequences
      of allelic variants. RESULTS: We identified two heterozygous PROKR2 mutations
      (p.Leu173Arg and p.Arg85His) previously reported in isolated hypogonadotroph
      hypogonadism and a novel PROKR2 variant (p.Ala51Thr) that, in contrast with both
      other mutations, did not impair receptor signaling activity. Three allelic
      variants of HESX1 were identified: the heterozygous p.Phe156Ser and the
      homozygous p.Arg109X mutations were functionally deleterious, whereas p.Ser67Thr
      was found as a rare allelic variant in association with p.Arg85His PROKR2
      mutation in the same patient. CONCLUSIONS: We report PROKR2 variants in
      congenital hypopituitarism with pituitary stalk interruption, suggesting a
      potential role of the prokineticin pathway in pituitary development.

PMID- 22466335
TI  - Orexigenic neuropeptide 26RFa: new evidence for an adaptive profile of appetite
      regulation in anorexia nervosa.
AB  - CONTEXT: Restrictive anorexia nervosa (AN) presents an adaptive appetite
      regulating profile including mainly high levels of ghrelin. Because this adaptive
      mechanism is not effective on food intake, other appetite-regulating peptides
      need to be explored. 26RFa is a hypothalamic neuropeptide that stimulates
      appetite, gonadotropin release, and bone metabolism. OBJECTIVE: The objective of
      the study was to evaluate the circadian levels of 26RFa in AN patients compared
      with healthy subjects, other eating disorders, and constitutional thinness (CT).
      DESIGN AND SETTINGS: This was a cross-sectional study performed in an endocrine
      unit and an academic laboratory. INVESTIGATED SUBJECTS: Five groups of age
      matched young women were included in the study: 19 restrictive AN, 10 AN with
      bingeing/purging episodes, 14 with CT, 10 bulimic, and 10 normal-weight controls.
      MAIN OUTCOME MEASURES: Twelve-point circadian profiles of plasma 26RFa levels
      were measured in each subject. RESULTS: Significant circadian variations of 26
      RFA were noticed in controls with higher values in the morning and abrupt
      decrease at noon. Twenty-four-hour mean 26RFa levels were significantly increased
      in restrictive AN and AN with bingeing/purging episodes (P < 0.001),
      predominantly in the afternoon and evening when compared with controls.
      Preprandial rises of 26 RFA were noticed in AN patients. Mean 26RFa levels trend
      to be higher in CT than in controls (P = 0.06) and significantly lower than in
      AN. The bulimic patients presented a circadian profile of 26RFa similar to that
      of controls. CONCLUSION: High levels of circulating 26RFa observed in AN patients
      might reflect an adaptive mechanism of the organism to promote energy intake and
      to increase fat stores in response to undernutrition.

PMID- 22466336
TI  - Clinical review. Comparative effectiveness of drug treatments to prevent
      fragility fractures: a systematic review and network meta-analysis.
AB  - CONTEXT: Osteoporosis and osteopenia are associated with increased fracture
      incidence. OBJECTIVE: The aim of this study was to determine the comparative
      effectiveness of different pharmacological agents in reducing the risk of
      fragility fractures. DATA SOURCES: We searched multiple databases through
      12/9/2011. STUDY SELECTION: Eligible studies were randomized controlled trials
      enrolling individuals at risk of developing fragility fractures and evaluating
      the efficacy of bisphosphonates, teriparatide, selective estrogen receptor
      modulators, denosumab, or calcium and vitamin D. DATA EXTRACTION: Reviewers
      working independently and in duplicate determined study eligibility and collected
      descriptive, methodological quality, and outcome data. DATA SYNTHESIS: This
      network meta-analysis included 116 trials (139,647 patients; median age, 64 yr;
      86% females and 88% Caucasians; median follow-up, 24 months). Trials were at low
      to moderate risk of bias. Teriparatide had the highest risk reduction of
      fractures (odds ratios, 0.42, 0.30, and 0.50 for hip, vertebral, and nonvertebral
      fractures, respectively) and the highest probability of being ranked first for
      efficacy (probabilities of 42, 49, and 79% for hip, vertebral, and nonvertebral
      fractures, respectively). However, differences to denosumab, zoledronate,
      risedronate, ibandronate, and alendronate were not statistically significant.
      Raloxifene and bazedoxifene were likely less effective, although these data were
      limited. Calcium and vitamin D were ineffective given separately but reduced the
      risk of hip fractures if given in combination (odds ratio, 0.81; 95% confidence
      interval, 0.68-0.96). CONCLUSIONS: Teriparatide, bisphosphonates, and denosumab
      are most effective in reducing the risk of fragility fractures. Differences in
      efficacy across drugs are small; therefore, patients and clinicians need to
      consider their associated harms and costs.

PMID- 22466337
TI  - Macro-thyrotropin: a case report and review of literature.
AB  - CONTEXT: Isolated elevation of TSH in the absence of thyroid symptoms can be very
      rarely caused by a macromolecule formed between TSH and Ig (macro-TSH),
      confounding the interpretation of thyroid function test results. OBJECTIVE: We
      described the use of several commonly available laboratory-based approaches to
      investigate an isolated TSH elevation [232 mIU/liter; free T(4), 10 pmol/liter
      (reference interval, 10.0-23.0 pmol/liter), Vitros platform] in a clinically
      euthyroid elderly gentleman, which led to the diagnosis of macro-TSH. METHODS AND
      RESULTS: TSH concentration of the patient was significantly lower (122 mIU/liter)
      when measured on the Advia Centaur platform. Serial dilution of the patient's
      sample showed a nonlinear increase in TSH recovery at increasing dilution
      (nonlinearity). Polyethylene glycol precipitation and mixing the patient's sample
      with a hypothyroid patient sample showed reduced TSH recovery, suggesting the
      presence of a high molecular weight interfering substance and excess TSH binding
      capacity, respectively. Heterophile blocking tube studies and rheumatoid factors
      were negative. Gel filtration chromatography demonstrated a TSH peak fraction
      that approximated the molecular size of IgG; together with the excess TSH binding
      capacity, this indicated the presence of TSH-IgG macro-TSH. A review of 12 macro
      TSH case reports showed that samples with macro-TSH produce over-recovery with
      dilution, return negative results on anti-animal and anti-heterophile blocking
      studies, and commonly have recovery of less than 20% when subjected to
      polyethylene glycol precipitation. CONCLUSION: Macro-TSH is an underrecognized
      laboratory interference. Routine laboratory techniques described above can help
      diagnose this rare entity. A close dialogue between the physician and the
      laboratory is important in approaching such cases.

PMID- 22466338
TI  - Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic
      fracture in middle-aged and elderly Chinese.
AB  - CONTEXT: Nonalcoholic fatty liver disease (NAFLD) has been considered as a
      hepatic manifestation of the metabolic syndrome and is associated with various
      metabolic abnormalities, which may link to an increased risk of osteoporotic
      fracture. However, epidemiological studies investigating the association between
      NAFLD and osteoporotic fracture were not available. OBJECTIVE: The objective of
      the study was to determine whether NAFLD associates with osteoporotic fracture.
      DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 7797
      Chinese adults aged 40 yr or older in the Jiading District, Shanghai, China. MAIN
      OUTCOME MEASURES: A questionnaire, anthropometric measurements, laboratory tests,
      and a hepatic ultrasonic examination were conducted. NAFLD was diagnosed by
      hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases.
      A history of fractures was collected with an interviewer-assisted questionnaire.
      Osteoporotic fractures were defined as fractures that occurred due to low-trauma
      in 2 yr prior to the study. RESULTS: Among men, the prevalence of osteoporotic
      fractures was significantly higher in those with NAFLD (3.6 vs. 1.7%, P = 0.003);
      however, no difference was found in women (3.4 vs. 2.6%, P = 0.14). The presence
      of NAFLD was significantly associated with increased odds of osteoporotic
      fracture among men (odds ratio 2.53; 95% confidence interval 1.26-5.07; P =
      0.009) after controlling for potential confounders. The significant associations
      were not detected in women. CONCLUSIONS: The presence of NAFLD was significantly
      associated with a recent history of osteoporotic fracture in middle-aged and
      elderly Chinese men.

PMID- 22466339
TI  - Clinical review. Kidney stones 2012: pathogenesis, diagnosis, and management.
AB  - CONTEXT: The pathogenetic mechanisms of kidney stone formation are complex and
      involve both metabolic and environmental risk factors. Over the past decade,
      major advances have been made in the understanding of the pathogenesis,
      diagnosis, and treatment of kidney stone disease. EVIDENCE ACQUISITION AND
      SYNTHESIS: Both original and review articles were found via PubMed search
      reporting on pathophysiology, diagnosis, and management of kidney stones. These
      resources were integrated with the authors' knowledge of the field. CONCLUSION:
      Nephrolithiasis remains a major economic and health burden worldwide.
      Nephrolithiasis is considered a systemic disorder associated with chronic kidney
      disease, bone loss and fractures, increased risk of coronary artery disease,
      hypertension, type 2 diabetes mellitus, and the metabolic syndrome. Further
      understanding of the pathophysiological link between nephrolithiasis and these
      systemic disorders is necessary for the development of new therapeutic options.

PMID- 22466340
TI  - Transforming growth factor beta1 (TGFbeta1) and progesterone regulate matrix
      metalloproteinases (MMP) in human endometrial stromal cells.
AB  - CONTEXT: Menstruation is preceded by progesterone withdrawal and endometrial
      matrix remodeling predominantly through induction of matrix metalloproteinases
      (MMP) and recruitment of invading neutrophils. DESIGN: Using endometrial tissues
      from women during various phases of the menstrual cycle, we found that MMP2,
      MMP9, and MMP11 were up-regulated in the late secretory phase/premenstrual phase.
      Because TGFbeta-responsive genes were also up-regulated in endometrium during
      this time, we tested the hypothesis that TGFbeta1 and progesterone regulate
      expression of MMP in human endometrial stromal cells (HESC). RESULTS: Treatment
      of HESC with TGFbeta1 resulted in marked increases in MMP2 and MMP11 mRNA and pro
      and active MMP2 activity. Progesterone inhibited TGFbeta1-induced stimulation of
      MMP2 and MMP11 through its nuclear hormone receptors. Interestingly, TGFbeta1
      also decreased progesterone receptor (PR)-A and PR-B in HESC with a more
      pronounced effect on PR-A. CONCLUSIONS: These data support the hypothesis that
      TGFbeta1 has endogenous anti-progestational effects in HESC and that the opposing
      effects of progesterone and TGFbeta1 are important in regulation of matrix
      integrity in human endometrium.

PMID- 22466341
TI  - Serum sclerostin and risk of hip fracture in older Caucasian women.
AB  - CONTEXT: Sclerostin, a protein secreted by osteocytes, inhibits bone formation.
      Individuals with genetic mutations that decrease the availability of sclerostin
      have very high bone mass. OBJECTIVE: The aim of this study was to examine the
      hypothesis that elevated serum sclerostin levels are associated with increased
      risk of hip fracture in older women. DESIGN, SETTING, AND PARTICIPANTS: This was
      a case-cohort study of a prospective, community-based cohort of 9704 women aged
      65 yr or older. Sclerostin levels were measured in serum collected in 1989-1990
      in 228 women with incident hip fractures and 227 women in a randomly selected
      sample; average follow-up time was 9.8 yr. RESULTS: Serum sclerostin levels were
      correlated with total hip bone mineral density (BMD; r = 0.27, P < 0.001). The
      risk of hip fracture increased across quartiles of serum sclerostin (test for
      trend, P < 0.001) and was significantly elevated among those in the fourth
      quartile (hazard risk 3.4, 95% confidence interval 1.7-7.0) compared with women
      in the lowest quartile, after adjusting for age, body mass index, estrogen use,
      history of fracture since age 50 yr, and total hip BMD. When dividing the cohort
      into eight groups by sclerostin quartile and median hip BMD, women with lower
      total hip BMD in the highest sclerostin quartile had a 22.3-fold (95% confidence
      interval 5.8-86.3) increased risk of fracture compared with women with higher
      total hip BMD in the lowest sclerostin quartile. CONCLUSIONS: We conclude that
      higher serum sclerostin levels are associated with a greater risk of hip
      fractures in older women. In addition, the risk of hip fracture is amplified when
      high sclerostin levels are combined with lower BMD.

PMID- 22466342
TI  - beta2-adrenergic receptor Thr164Ile polymorphism, obesity, and diabetes:
      comparison with FTO, MC4R, and TMEM18 polymorphisms in more than 64,000
      individuals.
AB  - CONTEXT: The beta(2)-adrenergic receptor (ADRB2) influences regulation of energy
      balance by stimulating catecholamine-induced lipolysis in adipose tissue. The
      rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence
      risk of obesity and subsequently diabetes. OBJECTIVE: We tested the hypothesis
      that the ADRB2rs1800888(Thr164Ile) polymorphism associates with risk of obesity
      and diabetes and compared effect sizes with those of FTO(rs9939609),
      MC4R(rs17782313), and TMEM18(rs6548238). DESIGN AND SETTING: We conducted a
      population-based cohort study in Copenhagen, Denmark. PARTICIPANTS: We genotyped
      more than 64,000 individuals from the Danish general population. MAIN OUTCOME
      MEASURES: We evaluated body mass index (BMI), obesity (BMI >=30 kg/m(2)), and
      diabetes. RESULTS: Rare allele frequencies were 0.02 for T for
      ADRB2rs1800888(Thr164Ile), 0.40 for A for FTOrs9939609, 0.25 for C for
      MC4Rrs17782313, and 0.20 for T for TMEM18rs6548238. For rare vs. common
      homozygotes, odds ratio for obesity was 3.32 (95% confidence interval = 1.08
      10.19) for ADRB2rs1800888(Thr164Ile), 1.42 (1.35-1.52) for FTOrs9939609, 1.18
      (1.06-1.30) for MC4Rrs17782313, and 1.28 (1.10-1.50) for TMEM18rs6548238 (common
      vs. rare). Corresponding odds ratios for diabetes were 1.85 (0.24-14.29), 1.22
      (1.07-1.39), 0.96 (0.80-1.16), and 1.61 (1.17-2.22), respectively. After
      adjustment for BMI, only TMEM18rs6548238 remained associated with diabetes. BMI
      was increased in rare vs. common homozygotes in FTOrs9939609, MC4Rrs17782313, and
      TMEM18rs6548238 (common vs. rare) but not in ADRB2rs1800888(Thr164Ile).
      CONCLUSIONS: Our results suggest that ADRB2rs1800888(Thr164Ile) rare vs. common
      homozygotes are not significantly associated with an increase in BMI measured
      continuously but may be associated with an increased risk of obesity. Also,
      TMEM18rs6548238 associated with risk of diabetes after adjustment for BMI. These
      findings need confirmation in other studies.

PMID- 22466344
TI  - Clinical review. Risk factors for low bone mass-related fractures in men: a
      systematic review and meta-analysis.
AB  - CONTEXT: Testing men at increased risk for osteoporotic fractures has been
      recommended. OBJECTIVE: The aim of this study was to estimate the magnitude of
      association and quality of supporting evidence linking multiple risk factors with
      low bone mass-related fractures in men. DATA SOURCES: We searched MEDLINE,
      EMBASE, Web of Science, SCOPUS and Cochrane CENTRAL through February 2010. We
      identified further studies by reviewing reference lists from selected studies and
      reviews. STUDY SELECTION: Eligible studies had to enroll men and quantitatively
      evaluate the association of risk factors with low bone density-related fractures.
      DATA EXTRACTION: Reviewers working independently and in duplicate determined
      study eligibility and extracted study description, quality, and outcome data.
      DATA SYNTHESIS: Fifty-five studies provided data sufficient for meta-analysis.
      The quality of these observational studies was moderate with fair levels of
      multivariable adjustment and adequate exposure and outcome ascertainment.
      Statistically significant associations were established for age, low body mass
      index, current smoking, excessive alcohol use, chronic corticosteroid use,
      history of prior fractures, history of falls, history of hypogonadism, history of
      stroke, and history of diabetes. Statistical heterogeneity of the meta-analytic
      estimates of all associations was significant except for chronic corticosteroid
      use. None of these associations were of large magnitude (i.e. adjusted odds
      ratios were generally <2). No evidence supporting a particular effective testing
      or screening strategy was identified. CONCLUSIONS: Multiple risk factors for
      fractures in men were identified, but their usefulness for stratifying and
      selecting men for bone density testing remains uncertain.

PMID- 22466343
TI  - Programmed death-1+ T cells and regulatory T cells are enriched in tumor-involved
      lymph nodes and associated with aggressive features in papillary thyroid cancer.
AB  - CONTEXT: Recurrent metastatic lymph node (LN) disease is common in patients with
      papillary thyroid cancer (PTC). Novel prognostic markers may be helpful in
      guiding a therapeutic approach. Our previous studies revealed that immune
      suppression is evident in PTC and associated with more severe disease. OBJECTIVE:
      To characterize the immune response to metastatic PTC, we assessed CD4(+) T cell
      polarization in LN. In addition, we investigated the role of programmed death-1
      (PD-1) and T cell exhaustion. DESIGN: Uninvolved (UILN) and tumor-involved lymph
      nodes (TILN) were sampled ex vivo by fine-needle biopsy. T cell subsets were
      identified by flow cytometry. In parallel, archived TILN specimens were
      characterized by immunofluorescence. SETTING: The study was conducted at the
      University of Colorado Hospital. PATIENTS: Data were collected on 94 LN from 19
      patients with PTC undergoing neck dissection. MAIN OUTCOME: T cell subset
      frequencies were compared in UILN and TILN and assessed for correlation with
      recurrent disease and extranodal invasion. RESULTS: Regulatory CD4(+) T cells
      (Treg) were enriched in TILN compared with UILN and further elevated in TILN from
      patients with recurrent disease. PD-1(+) T cells were present at high frequency
      in TILN and markedly enriched in TILN that showed evidence of extranodal
      invasion. In TILN, Treg frequency correlated with PD-1(+) T cell frequencies.
      Although PD-1(+) T cells produced interferon-gamma, they failed to fully down
      regulate CD27 and were not actively proliferating. CONCLUSIONS: Increased Treg
      and PD-1(+) T cell frequencies in LN may be indicative of aggressive recurrent
      PTC. Future prospective studies are necessary to determine the prognostic and
      therapeutic value of these findings in PTC.

PMID- 22466345
TI  - Joint effects of smoking and gene variants involved in sex steroid metabolism on
      hot flashes in late reproductive-age women.
AB  - BACKGROUND: Although smoking has a known association with hot flashes, the
      factors distinguishing smokers at greatest risk for menopausal symptoms have not
      been well delineated. Recent evidence supports a relationship between menopausal
      symptoms and variants in several genes encoding enzymes that metabolize
      substrates such as sex steriods, xenobiotics, and catechols. It is currently not
      known whether the impact of smoking on hot flashes is modified by the presence of
      such variants. OBJECTIVE: The objective of the study was to investigate the
      relationship between smoking and hot flash occurrence as a function of genetic
      variation in sex steroid-metabolizing enzymes. METHODS: A cross-sectional
      analysis of data from the Penn Ovarian Aging study, an ongoing population-based
      cohort of late reproductive-aged women, was performed. Smoking behavior was
      characterized. Single-nucleotide polymorphisms in five genes were investigated:
      COMT Val158Met (rs4680), CYP1A2*1F (rs762551), CYP1B1*4 (Asn452Ser, rs1800440),
      CYP1B1*3 (Leu432Val, rs1056836), and CYP3A4*1B (rs2740574). RESULTS: Compared
      with nonsmokers, European-American COMT Val158Met double-variant carriers who
      smoked had increased odds of hot flashes [adjusted odds ratio (AOR) 6.15, 95%
      confidence interval (CI) 1.32-28.78)]; European-American COMT Val158Met double
      variant carriers who smoked heavily had more frequent moderate or severe hot
      flashes than nonsmokers (AOR 13.7, 95% CI 1.2-154.9). European-American CYP 1B1*3
      double-variant carriers who smoked described more frequent moderate or severe hot
      flashes than nonsmoking (AOR 20.6, 95% CI 1.64-257.93) and never-smoking (AOR
      20.59, 95% CI 1.39-304.68) carriers, respectively. African-American single
      variant CYP 1A2 carriers who smoked were more likely to report hot flashes than
      the nonsmoking carriers (AOR 6.16, 95% CI 1.11-33.91). CONCLUSION: This is the
      first report demonstrating the effects of smoking within the strata of gene
      variants involved in sex steroid metabolism on hot flashes in late reproductive
      age women. The identification of individuals with a genetic susceptibility to
      smoking-related menopausal symptoms could contribute to interventions targeted at
      reducing reproductive morbidity both in the menopause and across the reproductive
      life course.

PMID- 22466346
TI  - Clinical inertia of discharge planning among patients with poorly controlled
      diabetes mellitus.
AB  - OBJECTIVE: We examined the effect of hospital admissions on the medical treatment
      of poorly controlled diabetes mellitus among Veterans Affairs (VA) patients.
      RESEARCH DESIGN AND METHODS: This retrospective cohort study included male
      patients admitted to one of three VA hospitals from July 1, 2002, to August 31,
      2009, who were receiving medication therapy for diabetes with hemoglobin A1c
      (HgbA1c) greater than 8.0%. The primary outcome was a change in preadmission and
      outpatient prescriptions for diabetes at hospital discharge. Covariates for
      multivariable logistic regression analysis of the primary outcome were defined a
      priori and retrieved from the electronic health record. RESULTS: Of 2025
      admissions for 1359 patients, 454 had some change in diabetes medications at
      discharge (rate of change 22.4%). In an adjusted analysis, higher preadmission
      HgbA1c [odds ratio (OR) 1.12 per 1.0 U increase; 95% confidence interval (CI)
      1.12-1.05; P < 0.001], higher mean blood glucose during admission (OR 1.07 per 10
      mg/dl increase; 95% CI 1.05-1.10; P < 0.0001), occurrence of inpatient
      hypoglycemia (blood glucose < 50 mg/dl; OR 1.82, 95% CI 1.32-2.51, P < 0.001),
      and inpatient basal insulin therapy (OR 1.71; 95% CI 1.25-2.35; P < 0.001) were
      associated with higher odds of change in therapy. A total of 656 admissions (32%)
      demonstrated aggregate clinical inertia with no change in therapy, no
      documentation of HgbA1c within 60 d of discharge, and no follow-up appointment
      within 30 d of discharge. CONCLUSIONS: In this multicenter, retrospective study
      of patients with poorly controlled diabetes and at least one hospitalization,
      less than a quarter received a change in outpatient diabetes therapy upon
      discharge, suggesting widespread clinical inertia. Nearly one third had no change
      in therapy or subsequent follow-up scheduled.

PMID- 22466347
TI  - Clinical and genetic characteristics of autoimmune polyglandular syndrome type 3
      variant in the Japanese population.
AB  - OBJECTIVE: Type 1 diabetes (T1D) is commonly associated with autoimmune thyroid
      disease (AITD), and the occurrence of both T1D and AITD in a patient is defined
      as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify
      the differences in the clinical and genetic characteristics of APS3v patients and
      T1D patients without AITD [T1D/AITD(-)] in the Japanese population.
      DESIGN/PATIENTS: Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients
      who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the
      present. RESULTS: A remarkable female predominance, a slow and older age onset of
      T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were
      observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age
      of T1D in APS3v patients was associated with a higher proportion of slow-onset
      T1D. Among the two major susceptible human leukocyte antigen (HLA) class II
      haplotypes in Japanese T1D, DRB1*0405-DQB1*0401, but not DRB1*0901-DQB1*0303, was
      associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not
      protective in patients with APS3v. The frequencies of the GG genotype in +49G>A
      and +6230G>A polymorphism in the CTLA4 gene were significantly higher in
      T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects.
      CONCLUSIONS: In conclusion, we found notable differences in the clinical and
      genetic characteristics of APS3v patients and T1D/AITD(-) patients in the
      Japanese population, and the differences in the clinical characteristics between
      the two groups may reflect distinct genetic backgrounds including the HLA DRB1
      DQB1 haplotypes and CTLA4 gene polymorphisms.

PMID- 22466348
TI  - Mifepristone, a glucocorticoid receptor antagonist, produces clinical and
      metabolic benefits in patients with Cushing's syndrome.
AB  - CONTEXT: Cushing's syndrome (CS) is a disorder associated with significant
      morbidity and mortality due to prolonged exposure to high cortisol
      concentrations. OBJECTIVE: Our objective was to evaluate the safety and efficacy
      of mifepristone, a glucocorticoid receptor antagonist, in endogenous CS. DESIGN
      AND SETTING: We conducted a 24-wk multicenter, open-label trial after failed
      multimodality therapy at 14 U.S. academic medical centers and three private
      research centers. PARTICIPANTS: Participants included 50 adults with endogenous
      CS associated with type 2 diabetes mellitus/impaired glucose tolerance (C-DM) or
      a diagnosis of hypertension alone (C-HT). INTERVENTION: Mifepristone was
      administered at doses of 300-1200 mg daily. MAIN OUTCOME MEASURES: We evaluated
      change in area under the curve for glucose on 2-h oral glucose test for C-DM and
      change in diastolic blood pressure from baseline to wk 24 for C-HT. RESULTS: In
      the C-DM cohort, an area under the curve for glucose (AUC(glucose)) response was
      seen in 60% of patients (P < 0.0001). Mean +/- sd glycated hemoglobin (HbA1c)
      decreased from 7.43 +/- 1.52% to 6.29 +/- 0.99% (P < 0.001); fasting plasma
      glucose decreased from 149.0 +/- 75.7 mg/dl (8.3 +/- 4.1 mmol/liter) to 104.7 +/-
      37.5 mg/dl (5.8 +/- 2.1 mmol/liter, P < 0.03). In C-HT cohort, a diastolic blood
      pressure response was seen in 38% of patients (P < 0.05). Mean weight change was 
      5.7 +/- 7.4% (P < 0.001) with waist circumference decrease of -6.78 +/- 5.8 cm (P
      < 0.001) in women and -8.44 +/- 5.9 cm (P < 0.001) in men. Overall, 87% (P <
      0.0001) had significant improvement in clinical status. Insulin resistance,
      depression, cognition, and quality of life also improved. Common adverse events
      were fatigue, nausea, headache, low potassium, arthralgia, vomiting, edema, and
      endometrial thickening in women. CONCLUSIONS: Mifepristone produced significant
      clinical and metabolic improvement in patients with CS with an acceptable risk
      benefit profile during 6 months of treatment.

PMID- 22466349
TI  - ACTH and cortisol response to Dex/CRH testing in women with and without
      premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian
      steroid replacement.
AB  - CONTEXT: During conditions of ovarian suppression, women with premenstrual
      dysphoria (PMD) experience abnormal behavioral responses to physiological levels
      of ovarian steroids. Although hypothalamic-pituitary-adrenal (HPA) axis
      dysregulation frequently accompanies depression, and ovarian steroids regulate
      HPA axis responsivity, the role of HPA axis dysregulation in PMD is not known. We
      hypothesized that women with PMD would show abnormalities of HPA axis function
      analogous to those reported in depressive illness, and that ovarian steroids
      would differentially regulate HPA axis function in women with PMD compared with
      asymptomatic controls (AC). OBJECTIVE: Our objective was to characterize the HPA
      axis response to physiological levels of estradiol and progesterone in women with
      PMD and AC. DESIGN AND SETTING: We conducted an open-label trial of the GnRH
      agonist depot Lupron with ovarian steroid replacement administered in a double
      blind crossover design in an outpatient clinic. PARTICIPANTS: Forty-three women
      (18 with prospectively confirmed PMD and 25 AC) participated. INTERVENTIONS:
      Women received Lupron for 6 months. After 3 months of hypogonadism, women
      received 5 wk each of estradiol (100-MUg patch daily) or progesterone
      (suppositories 200 mg twice daily). During each condition, combined dexamethasone
      suppression/CRH-stimulation tests and 24-h urinary free cortisol levels were
      performed. MAIN OUTCOME MEASURES: Plasma cortisol and ACTH levels were evaluated.
      RESULTS: HPA axis function was similar in PMD compared with AC. In all,
      progesterone significantly increased the secretion of cortisol compared with
      estradiol [area under the curve (t(74) = 3.1; P < 0.01)] and urinary free
      cortisol (t(74) = 3.2; P < 0.01) and ACTH compared with hypogonadism [area under
      the curve (t(74) = 2.4; P < 0.05)]. CONCLUSIONS: HPA axis regulation is normal in
      PMD, suggesting that the pathophysiology of PMD differs from major depression. As
      observed previously, progesterone but not estradiol up-regulates HPA axis
      function in women.

PMID- 22466350
TI  - Relative contributions of oligomenorrhea and hyperandrogenemia to the risk of
      metabolic syndrome in midlife women.
AB  - CONTEXT: Young reproductive-age women with irregular menses and androgen excess
      are at high risk for unfavorable metabolic profile; however, recent data suggest
      that menstrual regularity and hyperandrogenism improve with aging in affected
      women approaching menopause. OBJECTIVE: The objective of the study was to
      determine whether women with hyperandrogenemia (HA) and a history of
      oligomenorrhea (Oligo) are at an elevated risk for metabolic syndrome (MetS) at
      the early stages of menopausal transition. METHODS: Baseline data from 2543
      participants (mean age of 45.8 yr) in the Study of Women's Health Across the
      Nation were analyzed. Women with a lifetime history of more than one 3-month
      interval of nongestational and nonlactational amenorrhea were classified as
      having a history of Oligo. The highest tertile of serum testosterone was used to
      define HA. Women with normal serum androgens and eumenorrhea were used as the
      reference group. Logistic regression models generated adjusted odds ratios (AOR),
      controlling for age, ethnicity, body mass index, smoking, and study site.
      RESULTS: Oligo was associated with MetS only when coincident with HA [AOR of 1.93
      for Oligo and HA [95% confidence interval (CI) 1.17-3.17], AOR of 1.25 for Oligo
      and normal androgens (95% CI 0.81-1.93)]. In contrast, HA conferred a
      consistently significant risk for MetS, regardless of the menstrual frequency
      status [AOR of 1.48 for HA and eumenorrhea (95% CI 1.15-1.90)]. CONCLUSIONS: Our
      results suggest that HA but not history of Oligo is independently associated with
      the risk of prevalent MetS in pre- and perimenopausal women in their 40s.

PMID- 22466351
TI  - An unusual ectopic location of a parathyroid carcinoma arising within the thyroid
      gland.
AB  - INTRODUCTION: Parathyroid carcinomas are very rare tumors and may arise in the
      normally located or ectopic gland. The latter present certain diagnostic
      difficulties, and there are no specific guidelines on their management. We
      present a case of parathyroid carcinoma arising within an ectopically located
      intrathyroid gland and discuss the diagnosis, management, and difficulties
      encountered. Furthermore, we review all six previously reported cases of this
      rare event and demonstrate the patterns in presentation, as well as the
      differences in management. CASE PRESENTATION: A 39-yr-old male presented with a
      right neck mass with biochemical derangement suggestive of a parathyroid lesion.
      However, radiological investigations were inconclusive as to the true nature of
      this lesion because they demonstrated a mass within the right thyroid lobe. A
      sestamibi (99m)technetium subtraction study was performed, which suggested an
      intrathyroid parathyroid carcinoma. The patient underwent successful surgical
      intervention. CONCLUSION: Although rare, ectopically located parathyroid glands
      can harbor malignant disease. Those located within the thyroid gland can be
      difficult to diagnose, and thus a combination of radiological modalities,
      including sestamibi (99m)technetium studies, need to be utilized. Although
      surgical resection is the most effective treatment, there are no specific
      guidelines as to the radicality of such treatment.

PMID- 22466352
TI  - On "Effectiveness of stretch for the treatment and prevention of contractures..."
      Katalinic OM, Harvey LA, Herbert RD. Phys Ther. 2011;91:11-24.

PMID- 22466354
TI  - Influence of environmental ammonia on the production of nitric oxide and
      expression of inducible nitric oxide synthase in the freshwater air-breathing
      catfish (Heteropneustes fossilis).
AB  - Nitric oxide (NO) is a highly versatile and unique ubiquitous signaling molecule,
      and is known to play diverse physiological functions in mammals including those
      of adaptation to various stresses. The present study reports on the influence of
      exposure to high external ammonia (HEA) on the production of nitric oxide (NO)
      and the expression of inducible nitric oxide synthase (iNOS), that produces NO
      from l-arginine in the freshwater air-breathing catfish (Heteropneustes
      fossilis), which is reported to tolerate a very HEA. Some levels of NO were found
      to be present in all the tissues and also in plasma of control fish, which
      further enhanced significantly in fishes treated with high concentrations of
      environmental ammonia (25 and 50 mM ammonium chloride) for 7 days, accompanied by
      more efflux of NO from the perfused liver. This was accomplished by the induction
      of iNOS activity in different tissues of fish exposed to HEA, which otherwise was
      not detectable in control fish. Exposure to 25 mM ammonium chloride also led to a
      significant expression of iNOS protein in different tissues, followed by further
      increase at 50mM ammonium chloride. Further, there was an increase in the
      expression of iNOS mRNA in ammonia-treated fish, thus suggesting that the
      expression of iNOS gene under hyper-ammonia stress was probably regulated at the
      transcriptional level. Immunocytochemical analysis indicated that the expression
      of iNOS in different tissues was zonal specific and not expressed uniformly
      throughout the organ. Hyper-ammonia stress also led to activation and nuclear
      translocation of nuclear factor kappaB (NFkappaB) in hepatic cells. These results
      suggest that the activation of iNOS gene under hyper-ammonia stress was probably
      mediated through the activation of one of the major transcription factors, the
      NFkappaB. This is the first report of ammonia-induced expression of iNOS gene,
      iNOS protein expression leading to more generation of NO under hyper-ammonia
      stress in any teleosts.

PMID- 22466353
TI  - A potential role for differential contractility in early brain development and
      evolution.
AB  - Differences in brain structure between species have long fascinated evolutionary
      biologists. Understanding how these differences arise requires knowing how they
      are generated in the embryo. Growing evidence in the field of evolutionary
      developmental biology (evo-devo) suggests that morphological differences between
      species result largely from changes in the spatiotemporal regulation of gene
      expression during development. Corresponding changes in functional cellular
      behaviors (morphogenetic mechanisms) are only beginning to be explored, however.
      Here we show that spatiotemporal patterns of tissue contractility are sufficient
      to explain differences in morphology of the early embryonic brain between
      disparate species. We found that enhancing cytoskeletal contraction in the
      embryonic chick brain with calyculin A alters the distribution of contractile
      proteins on the apical side of the neuroepithelium and changes relatively round
      cross-sections of the tubular brain into shapes resembling triangles, diamonds,
      and narrow slits. These perturbed shapes, as well as overall brain morphology,
      are remarkably similar to those of corresponding sections normally found in
      species such as zebrafish and Xenopus laevis (frog). Tissue staining revealed
      relatively strong concentration of F-actin at vertices of hyper-contracted cross
      sections, and a finite element model shows that local contraction in these
      regions can convert circular sections into the observed shapes. Another model
      suggests that these variations in contractility depend on the initial geometry of
      the brain tube, as localized contraction may be needed to open the initially
      closed lumen in normal zebrafish and Xenopus brains, whereas this contractile
      machinery is not necessary in chick brains, which are already open when first
      created. We conclude that interspecies differences in cytoskeletal contraction
      may play a larger role in generating differences in morphology, and at much
      earlier developmental stages, in the brain than previously appreciated. This
      study is a step toward uncovering the underlying morphomechanical mechanisms that
      regulate how neural phenotypic differences arise between species.

PMID- 22466355
TI  - A novel report of metallothioneins in fish bile: SDS-PAGE analysis,
      spectrophotometry quantification and metal speciation characterization by liquid
      chromatography coupled to ICP-MS.
AB  - Metallothioneins (MT) are a validated biomarker for metal exposure. In fish they
      are usually determined in the liver, while some studies have observed MT in
      kidney, muscle and gills. There are, however, no reports on MT in fish bile. This
      study aimed to verify if these proteins are present in fish bile, if they can be
      used as biomarkers for metal exposure and to characterize the metal speciation
      present in the different species. Three independent methods to verify MT presence
      in fish bile were conducted: 1D/2D gel electrophoresis, spectrophotometric
      analyses and SEC-HPLC-ICP-MS. Results show that all methods verified the presence
      of these proteins in fish bile, while SEC-HPLC-ICP-MS also characterized also
      characterized metals responsible for the contamination of the studied sites.
      Quantification was successfully conducted by two methods, densitometry (1D
      electrophoresis) and spectrophotometry, and the data indicates that bile MTs
      follow the same trend as in liver. Therefore, Biliary MT show the potential to be
      used the same way as MT from other matrices in metal exposure studies, with the
      advantage of being a simpler matrix and showing the possibility of not
      sacrificing the animals, as chronic duct cannulation is available.

PMID- 22466356
TI  - Quantitatively evaluating detoxification of the hepatotoxic microcystins through
      the glutathione and cysteine pathway in the cyanobacteria-eating bighead carp.
AB  - Glutathione (GSH) and cysteine (Cys) conjugation have long been recognized to be
      important in the detoxification of microcystins (MCs) in animal organs, however,
      studies quantitatively estimating this process are rare, especially those
      simultaneously determining multiple toxins and their metabolites. This paper, for
      the first time, simultaneously quantified MC-LR (leucine arginine), MC-RR
      (arginine arginine), MCLR-GSH/Cys and MCRR-GSH/Cys in the liver, kidney,
      intestine and muscle of the cyanobacteria-eating bighead carp i.p. injected with
      two doses of MCs using liquid chromatography electrospray ionization mass
      spectrometry (LC-ESI-MS). MCLR-Cys and MCRR-Cys content were much higher in
      kidney than in liver, intestine and muscle, suggesting the organotropism to
      kidney, while MCLR-GSH and MCRR-GSH were always below the detection limit.
      Bighead carp effectively metabolized MC-LR and MC-RR into the cysteine conjugates
      in kidney, as the ratios of MCLR-Cys to MC-LR and MCRR-Cys to MC-RR reached as
      high as 9.04 and 19.10, respectively. MC-LR and MC-RR were excreted mostly in the
      form of MCLR/RR-Cys rather than MCLR/RR-GSH, while MCs-GSH might act as mid
      metabolites and changed to the more stable MCs-Cys rapidly. Cysteine conjugation
      of MCs appears to be an important biochemical mechanism for the cyanobacteria
      eating fish to resist toxic cyanobacteria. A comparison of such detoxification
      mechanisms between fish and mammals would be interesting in the future studies.

PMID- 22466358
TI  - Exposure-dose-response of Anadara trapezia to metal contaminated estuarine
      sediments. 2. Lead spiked sediments.
AB  - The composition of near shore marine environments is increasingly being altered
      by contaminants from human activities. The ability of lead, which has no known
      biological function, to mimic biologically essential metals makes it one of the
      most toxic to marine biota. The relationship between lead exposure, dose and
      response was investigated in Anadara trapezia exposed for 56 days to lead spiked
      sediment (100 and 300 MUg/g dry mass). Lead tissue concentrations of the 300
      MUg/g exposed A. trapezia doubled in the last 2 weeks of exposure with final lead
      tissue concentrations of exposed organisms of 1 and 12 MUg/g, respectively.
      Tissue lead accumulation of exposed organisms followed the pattern
      haemolymph>gill>hepatopancreas during much of the 56 day exposure. Between 30 and
      69% of accumulated lead in the gill and hepatopancreas was detoxified and fairly
      evenly distributed between the metal rich granule and the metallothionein like
      protein fractions. Approximately half of the biologically active lead in both
      tissues was in the mitochondrial fraction which showed increased cytochrome c
      oxidase activity in lead exposed organisms. There was a reduction in GPx
      activity, an associated increase in total glutathione concentrations and reduced
      GSH:GSSG ratios due to a build up of oxidised glutathione. These changes in the
      glutathione pathway were reflected in the total antioxidant capacity of lead
      exposed A. trapezia which were significantly reduced compared to control
      organisms. Increased lead exposure significantly increased lipid peroxidation,
      lysosomal destabilisation and frequency of micronuclei. A significant exposure
      dose-response relationship for A. trapezia exposed to lead enriched sediments
      indicates that elevated sediment lead concentrations have the potential to
      increase biologically active lead burdens and impair the antioxidant reduction
      capacity leading to a series of associated effects from lipid peroxidation to
      cellular perturbation and genotoxic damage.

PMID- 22466357
TI  - Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor.
AB  - Daphnia pulex is the first crustacean to have its genome sequenced. The genome
      project provides new insight and data into how an aquatic crustacean may respond
      to environmental stressors, including toxicants. We cloned Daphnia pulex HR96
      (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear
      receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to
      phenobarbital exposure and has been hypothesized as a toxicant receptor.
      Therefore, we set up a transactivation assay to test whether DappuHR96 is a
      promiscuous receptor activated by xenobiotics and endobiotics similar to the
      constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR).
      Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96
      is a promiscuous toxicant receptor activated by a diverse set of chemicals such
      as pesticides, hormones, and fatty acids. Several environmental toxicants
      activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and
      methane arsonate. We also observed repression of HR96 activity by chemicals such
      as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested
      activated or inhibited HR96. Interestingly, unsaturated fatty acids were common
      activators or inhibitors of HR96 activity, indicating a link between diet and
      toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and
      oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha
      linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two
      distinct sets of lipids perform opposing roles in Daphnia physiology. This also
      provides a putative mechanism by which the ratio of dietary unsaturated fats may
      affect the ability of an organism to respond to a toxic insult. In summary, HR96
      is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

PMID- 22466360
TI  - Short stature is an independent risk marker for mortality and incident coronary
      heart disease only in women: a structural relationship?
AB  - OBJECTIVE: We evaluated the associations of short stature with coronary heart
      disease (CHD) risk or overall mortality, which vary with sex and ethnicity/race.
      METHODS: Such associations were studied prospectively at a mean 13.5-years'
      follow-up in a population-based sample of 3394 Turkish adults (mean age 44+/-11
      years) using Cox proportional hazards models. Covariates of height were sought in
      sex-specific tertiles. RESULTS: Height averaged 162.7+/-6.5 cm. Age-adjusted
      estimated marginal means for serum triglycerides, C-reactive protein and
      complement C3 in women (but not men) were significantly higher with decreasing
      height tertiles. In sex- and age-adjusted models, height was associated in men
      with neither incident CHD, nor death. In women, 1-SD increment (6.5 cm) in height
      only tended to marginal inverse association with CHD, but predicted significantly
      all-cause death (HR 0.83, 95% CI 0.59-0.98); HR attenuated only marginally after
      further adjustment for family income bracket, smoking status, alcohol usage,
      systolic blood pressure, serum high-density lipoprotein (HDL)- and non HDL
      cholesterol. A threshold below 160 cm of female height doubled the adjusted risk
      of death compared to taller women. CONCLUSION: In contrast to men, short stature
      in Turkish women tends to be an independent risk marker for CHD, and height below
      160 cm is a strong marker of death. Gender-specific early-life influences
      enhancing pro-inflammatory state may affect death and future CHD.

PMID- 22466361
TI  - Elevated pentraxin-3 levels are related to blood pressure levels in hypertensive
      patients: an observational study.
AB  - OBJECTIVE: In this study, relationship between systolic and diastolic blood
      pressure and pentraxin-3 (PTX3) levels in hypertensive patients was investigated.
      METHODS: Overall, 80 patients with stage 1 hypertension between 40-61 years of
      age without any disease and 80 healthy volunteers were included to the study.
      Blood samples obtained to measure PTX3 levels and biochemical analysis.
      Relationship between PTX3 levels and clinical and biochemical parameters were
      analyzed using multivariate regression analysis. RESULTS: Although systolic and
      diastolic blood pressures were significant different, there were no differences
      regarding age and gender between hypertensives and normotensives. In each group,
      significant statistical differences were found between PTX3 and CRP levels (PTX3
      (ng/mL) 35.25+/-5.45 and 0.27+/-0.24, p<0.001; CRP (mg/dL) 10.03+/-5.81 and
      4.30+/-3.38, p<0.001; in hypertensive and normotensive groups respectively). It
      was observed that increase in PTX3 levels accompanies the increase in systolic
      and diastolic blood pressures (r2=0.78). It was observed that PTX3 levels are not
      effected from CRP, lipid levels and body mass index (p>0.05). On multivariate
      regression analysis PTX3 was found to strongly affect blood pressure (beta=0.82,
      95% CI 0.644-0.799, p<0.001, and beta=0.84, 95% CI 0.422-0.799, p<0.001,
      respectively for systolic and diastolic blood pressures), CRP and total
      cholesterol are found to affect moderately (beta=0.115-0.265, 95% CI 0.101-0.572,
      p<0.05 and beta=0.107-0.141, 95% CI 0.041-0.110, p<0.05, respectively).
      CONCLUSION: This study showed that PTX3 levels are higher in newly diagnosed
      hypertensive patients than in healthy individuals. In addition, it was noticed
      that increased PTX3 levels causes increase in systolic and diastolic blood
      pressures.

PMID- 22466362
TI  - Inflammation and hypertension: new clinical information on pentraxin-3.

PMID- 22466363
TI  - [The relation of serum paraoxonase-1 activity with isolated coronary artery
      ectasia: an observational study].
AB  - OBJECTIVE: Coronary artery ectasia (CAE) is a congenital or acquired anomaly
      characterized with localized or diffuse dilatations of coronary arteries.
      Paraoxonase (PON-1) is a high-density lipoprotein-cholesterol (HDLC) associated
      antioxidant enzyme that prevents atherosclerosis. The aim of this study was to
      investigate serum paraoxonase-1 enzyme activity (SPA) in patients with CAE in
      comparison patients with coronary artery disease (CAD) and normal coronary
      arteries. METHODS: We have evaluated 44 patients with isolated IKAE, 40 cases
      with normal coronary arteries (NCA), 40 cases with critical CAD (CAD) and 40
      cases with minimal CAD (MCAD) in this cross-sectional observational study.
      Demographic and biochemical data of patients were collected. SPA was determined
      spectrophotometrically. Among-group comparisons, ANOVA, Kruskal-Wallis and Chi
      square tests were used; Bonferroni test was used for post-hoc analysis, Pearson's
      correlation analysis to determine the parameters associated with the SPA.
      RESULTS: There were no differences among groups with regard to age, sex, presence
      of diabetes, hypertension and smoking (p>0.05 for all). The highest HDLC was
      detected in patients with NCA and lowest HDLC was detected in patients with CAD
      (respectively 52+/-15 mg/dL; 41+/-16 mg/d L, p=0.021). CAD and CAE groups were
      similar with respect to HDLC levels (p>0.05). The highest SPA level was detected
      in patients with NKA and the lowest SPA level was detected in patients with CAD
      (respectively 250.78+/-59.37U/L; 163.39+/-49.28 U/L, p=0.005). CAD and CAE groups
      were similar with respect to SPA levels (p>0.05). CONCLUSION: Both decreased SPA
      and decreased HDLC levels are closely related to the development of the CAE
      similar to CAD.

PMID- 22466364
TI  - Carotid-femoral pulse wave velocity in patients with isolated coronary artery
      ectasia: an observational study.
AB  - OBJECTIVE: Carotid-femoral pulse wave velocity (PWV), the current "gold-standard"
      measure of arterial stiffness, has emerged as an important independent predictor
      of cardiovascular events. The increased PWV is recognized as an indicator of
      atherosclerosis. The relationship between isolated coronary artery ectasia (CAE)
      and carotid-femoral PWV has not been well-described. The aim of our study was to
      assess this relation. METHODS: Thirty-four patients with isolated CAE without any
      visible coronary stenosis and 24 control subjects with angiographically normal
      coronary arteries were enrolled to this cross-sectional observational study.
      Applanation tonometry was applied to assess the carotid-femoral PWV. Statistical
      analyses were performed by Mann-Whitney U and Chi-square tests. Multiple linear
      regression analysis was used for the evaluation of the relations of parameters.
      RESULTS: The baseline clinical and laboratory parameters of the both groups were
      similar. Patients with isolated CAE had significantly higher carotid-femoral PWV
      compared to control subjects (10.5+/-2.4 vs 9.2+/-1.7 m/s, p=0.02). In multiple
      regression analysis, age (beta=0.23, 95% CI=0.001-0.094, p=0.04), number of
      ectatic vessels (beta=0.24, 95% CI=0.044-1.07, p=0.03), and systolic blood
      pressure (beta=0.52, 95% CI=0.028-0.1, p=0.001) were found independently related
      to PWV. CONCLUSION: We have shown an association between increased carotid
      femoral PWV and isolated CAE, suggesting that atherosclerosis may be involved in
      the pathogenesis of isolated CAE without any coronary stenosis in the adult
      population.

PMID- 22466365
TI  - Evaluation of subclinical left ventricular systolic dysfunction in patients with
      obstructive sleep apnea by automated function imaging method; an observational
      study.
AB  - OBJECTIVE: We aimed to evaluate the subclinical left ventricular (LV) systolic
      dysfunction with the automated function imaging method (AFI) based on speckle
      tracking echocardiography (STE) in obstructive sleep apnea patients (OSA) with
      normal left ventricular ejection fraction (LVEF) and without any confounding
      disease that can cause myocardial dysfunction. METHODS: Twenty-one healthy
      individuals and 58 OSA patients were included in this observational cross
      sectional study. According to the severity of disease, OSA patients were examined
      in three groups; mild, moderate and severe OSA. Apical 2-, 3- and 4- chamber
      images were obtained for AFI evaluation. The global systolic longitudinal strain
      (GLS) values were determined for each view, and averages of these were used in
      comparison of the patient groups. One-way ANOVA, Kruskal-Wallis, Pearson
      correlation tests and linear regression analysis were used for statistical
      analysis. RESULTS: The GLS values of the OSA patients were lower than of the
      healthy individuals and these values were decreased along with the OSA severity
      (Healthy:-25.58+/--2.16%, Mild:-23.93+/--3.96%, Moderate:-21.27+/--2.60%, Severe:
      16.94+/--2.66%, respectively). The difference was significant between moderate
      OSA patients and healthy individuals, and significant between severe OSA patients
      and all other groups (p<0.03). The apnea-hypopnea index was found to be
      correlated with the GLS (beta=-0.659, 95% CI: 0.09-0.17, p<0.001). CONCLUSION:
      Longitudinal LV mechanics in OSA patients with normal LVEF are deteriorated in
      the subclinical stage being associated with the severity of disease. AFI can be
      used as an effective and safe method in the determination of subclinical
      myocardial dysfunction in OSA patients, because it is semi-automated and easy to
      use with a short analysis time.

PMID- 22466367
TI  - Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive
      constituents of the bark of Magnolia officinalis.
AB  - Magnolol and honokiol, main active compounds from the bark of Magnolia
      officinalis, have been found to have various pharmacological actions, including
      anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties,
      without appreciable toxicity. Recently, the anti-tumor activity of magnolol and
      honokiol has been extensively investigated. Magnolol and honokiol were found to
      possess anti-tumor activity by targeting the apoptosis pathways, which have been
      considered as targets for cancer therapies. This review will focus on the
      mechanisms by which magnolol and honokiol act on apoptosis pathways in cancer
      that have been characterized thus far, including the death receptor mediated
      pathway, mitochondria-mediated pathway, caspase-mediated common pathway, and
      regulation of apoptosis-related proteins. These breakthrough findings may have
      important implications for targeted cancer therapy and modern applications of
      traditional Chinese medicine.

PMID- 22466366
TI  - SPEECHLESS integrates brassinosteroid and stomata signalling pathways.
AB  - Stomatal formation is regulated by multiple developmental and environmental
      signals, but how these signals are integrated to control this process is not
      fully understood. In Arabidopsis thaliana, the basic helix-loop-helix
      transcription factor SPEECHLESS (SPCH) regulates the entry, amplifying and
      spacing divisions that occur during stomatal lineage development. SPCH activity
      is negatively regulated by mitogen-activated protein kinase (MAPK)-mediated
      phosphorylation. Here, we show that in addition to MAPKs, SPCH activity is also
      modulated by brassinosteroid (BR) signalling. The GSK3/SHAGGY-like kinase BIN2
      (BR INSENSITIVE2) phosphorylates residues overlapping those targeted by the
      MAPKs, as well as four residues in the amino-terminal region of the protein
      outside the MAPK target domain. These phosphorylation events antagonize SPCH
      activity and limit epidermal cell proliferation. Conversely, inhibition of BIN2
      activity in vivo stabilizes SPCH and triggers excessive stomatal and non-stomatal
      cell formation. We demonstrate that through phosphorylation inputs from both
      MAPKs and BIN2, SPCH serves as an integration node for stomata and BR signalling
      pathways to control stomatal development in Arabidopsis.

PMID- 22466368
TI  - Agents that induce pseudo-allergic reaction.
AB  - Pseudo-allergic reactions may result from the activation of inflammatory or
      anaphylactic mechanisms independent of antigen-specific immune responses. Recent
      statistics show that pseudo-allergic reactions may represent as high as two
      thirds of all immediate hypersensitivity reactions, implying a great amount of
      morbidity and numerous health care costs. In this review, we concentrate on
      agents mediating pseudo-allergic reactions and evaluate accurately the available
      information on their modes of action. The agents discussed here are divided into
      three types: (i) Direct mast cell activators, which may activate mast cells in an
      IgE-independent manner, such as opioid drugs, basic secretagogues and calcium
      ionophore A23187; (ii) Complement activators, including liposomes, radiocontrast
      media and Cremophor EL, which may activate the complement system by different
      pathways: the classical pathway, the mannose-binding lectin pathway or the
      alternative pathway; (iii) Nonsteroidal anti-inflammatory drugs, which may
      inhibit the function of cyclooxygenase-1, resulting in the occurrence of adverse
      reactions. In addition, nonclinical detection methods of pseudo-allergic
      reactions are also reviewed in order to supply valuable information for clinical
      diagnosis.

PMID- 22466369
TI  - Design, synthesis, anticonvulsant screening and 5HT<sub>1A/2A</sub> receptor
      affinity of N(3)-substituted 2,4-imidazolidinediones and oxazolidinediones.
AB  - In the present study, a series of N(3)-substituted 2,4-imidazolidinediones and
      oxazolidinediones derivatives (1-16) were synthesized and tested for
      anticonvulsant activity using the maximal electroshock seizure test. Affinity
      towards receptor (5-HT<sub>1A/2A</sub>) was also studied. Their neurotoxicity was
      determined using the rotarod test. Structures of compounds were confirmed by
      spectroscopic methods. Compounds 1, 2, 5, 7, 9, and 10 exhibited significant
      anticonvulsant activity as compared to the standard drug phenytoin. Affinity
      toward receptor (5-HT<sub>1A/2A</sub>) was studied in vivo for compounds 1, 2, 5,
      7, 9, and 10. Rectal body temperature, lower lip retractions and head twitch
      responses in Wistar rats/albino mice were determined for this purpose. The tested
      compounds showed affinity for 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> receptors
      (agonists/antagonists and presynaptic/postsynaptic). Replacement of piperazine by
      aniline derivatives provides good outcomes in terms of affinity for 5
      HT<sub>1A/2A</sub>.

PMID- 22466370
TI  - Anti-Candida and radical scavenging activities of essential oils and oleoresins
      of Zingiber officinale Roscoe and essential oils of other plants belonging to the
      family Zingiberaceae.
AB  - Essential oils of young and mature rhizomes, air-dried and steamed rhizomes, and
      seed rhizomes of Zingiber officinale Roscoe (ginger) were prepared, and their
      inhibition of filamentation by Candida albicans was examined. Ginger essential
      oils, and particularly those from seed and air-dried rhizomes, had potent
      inhibitory activity compared to ginger oleoresins obtained by ethanol and
      hypercritical carbon dioxide extraction and essential oils of 5 other plants in
      the family Zingiberaceae. Of the constituents, [6]-shogaol was most active
      against filament formation and growth of C. albicans, followed by citral and [6]
      gingerol. Ginger oleoresin, and especially that obtained by ethanol extraction,
      with a high [6]-gingerol content exhibited potent scavenging activity against 1,1
      diphenyl-2-picrylhydrazyl radicals in comparison to essential oils of ginger and
      other Zingiberaceae plants.

PMID- 22466371
TI  - Development of microemulsion of a potent anti-tyrosinase essential oil of an
      edible plant.
AB  - The aim of this study is to develop a microemulsion product from a plant
      essential oil having the highest anti-tyrosinase activity. The in vitro anti
      tyrosinase activity of six essential oils extracted from six edible plants was
      compared. The oil of Cymbopogon citratus demonstrated the highest activity which
      was significantly nontoxic to normal human cells. The GC-MS data indicated that
      geranial and neral are the major compounds in the oil. The phase diagram composed
      of C. citrates oil, water, and surfactant mixture was conducted by a titration
      method. Ethyl alcohol was found to be the most suitable cosurfactant for the C.
      citrates oil microemulsion. The results revealed that the amount of oil and water
      played an important role in microemulsion conductivity and type. The most
      desirable o/w type of C. citratus oil microemulsion was found to be composed of
      20% oil, 30% water, and 50% surfactant mixture of a 2:1 weight ratio of Tween 20
      and ethyl alcohol.

PMID- 22466372
TI  - Initial characterization of D-cycloserine for future formulation development for
      anxiety disorders.
AB  - The purpose of this study is to characterize D-cycloserine (DCS) physicochemical
      properties to facilitate future formulation development of DCS for anxiety
      disorders. A stability-indicating HPLC assay method for the quantitation of DCS
      was developed and calibrated to be used for this study. The partition coefficient
      was determined and compared with the predicted value. The solution stability of
      DCS was studied under various pH (2.0-11.5) and ionic strengths of 10 and 20 mM
      at physiological temperature of 37 degrees C. The 250 mg capsule was compounded
      to the nominal strength of 50 mg used for anxiety disorders. These capsules were
      then put under stability. The in vitro dissolution was also carried out at 37
      degrees C as per the United States Pharmacopeia (USP) guidelines. The partition
      coefficient value (Kp) determined for the DCS was log Kp = -2.89 +/- 0.06 (n =
      6). The pH-solution stability profile shows that DCS has maximum stability under
      alkaline conditions. The maximum rate of degradation was seen at pH of 4.7. The
      mean percent recovery of DCS from the capsules compounded to strength of 50 mg
      was 100.3 +/- 1.4. The stability study of the reformulated capsules concluded
      that reformulated DCS is stable for at least one year at room temperature. The in
      vitro dissolution illustrates that all the DCS is released from the capsules in
      10 min. The present characterization of DCS study will serve as guidance for the
      future directions regarding the reformulation of DCS in order to be used in
      anxiety disorders.

PMID- 22466373
TI  - Cervical and thoracic mobilization versus manipulation for mechanical neck pain.
      Letter.

PMID- 22466374
TI  - Examining the sublineage structure of Mycobacterium tuberculosis complex strains
      with multiple-biomarker tensors.
AB  - Strains of the Mycobacterium tuberculosis complex (MTBC) can be classified into
      coherent lineages of similar traits based on their genotype. We present a tensor
      clustering framework to group MTBC strains into sublineages of the known major
      lineages based on two biomarkers: spacer oligonucleotide type (spoligotype) and
      mycobacterial interspersed repetitive units (MIRU). We represent genotype
      information of MTBC strains in a high-dimensional array in order to include
      information about spoligotype, MIRU, and their coexistence using multiple
      biomarker tensors. We use multiway models to transform this multidimensional data
      about the MTBC strains into two-dimensional arrays and use the resulting score
      vectors in a stable partitive clustering algorithm to classify MTBC strains into
      sublineages. We validate clusterings using cluster stability and accuracy
      measures, and find stabilities of each cluster. Based on validated clustering
      results, we present a sublineage structure of MTBC strains and compare it to the
      sublineage structures of SpolDB4 and MIRU-VNTRplus.

PMID- 22466375
TI  - Musculoskeletal pain and psychological distress in hospital patient care workers.
AB  - PURPOSE: The aim of the study was to assess the association of psychological
      distress and musculoskeletal pain, how it is related to pain interference with
      work and multiple pain areas, and potential differences between the different
      pain areas in hospital patient care workers. METHODS: Data were collected from a
      cross-sectional survey of patient care workers (n = 1,572) from two large
      hospitals. RESULTS: Patient care workers with musculoskeletal pain reported
      significantly more psychological distress than those without pain. Psychological
      distress was significantly related to pain interference with work, even after
      adjusting for pain and demographics (OR = 1.05; CI = 1.01-1.09). The association
      was strongest for those with both upper- and lower body pain (OR = 1.12; CI =
      1.06-1.18). Psychological distress was also independently associated with
      multiple pain areas. CONCLUSIONS: Psychological distress was found to be higher
      in workers with musculoskeletal pain, and highest among workers with both upper
      and lower body pain. Distress was further significantly associated with pain
      interference with work as well as number of pain areas. The findings may be
      followed up with a longitudinal design to better determine the direction of the
      associations, and to investigate if psychological distress increases the risk of
      work disability and injuries.

PMID- 22466376
TI  - Happy but still focused: failures to find evidence for a mood-induced widening of
      visual attention.
AB  - In models of affect and cognition, it is held that positive affect broadens the
      scope of attention. Consistent with this claim, previous research has indeed
      suggested that positive affect is associated with impaired selective attention as
      evidenced by increased interference of spatially distant distractors. However,
      several recent findings cast doubt on the reliability of this observation. In the
      present study, we examined whether selective attention in a visual flanker task
      is influenced by positive mood induction. Across three experiments, positive
      affect consistently failed to exert any impact on selective attention. The
      implications of this null-finding for theoretical models of affect and cognition
      are discussed.

PMID- 22466377
TI  - Children--start your motors!

PMID- 22466379
TI  - Effects of power wheelchairs on the development and function of young children
      with severe motor impairments.
AB  - PURPOSE: The purpose of this pilot randomized controlled study was to identify
      any effects of power wheelchairs on the development and function of young
      children with severe motor impairments. METHODS: Participants were 28 children
      with various diagnoses, aged 14 to 30 months when they entered the study. The
      Battelle Developmental Inventory (BDI), Pediatric Evaluation of Disability
      Inventory, and Early Coping Inventory were administered at entry and after 12
      months. RESULTS: The on-protocol analysis comparing median change scores showed
      the experimental groups' BDI receptive communication scores, and their Pediatric
      Evaluation of Disability Inventory mobility functional skills, mobility caregiver
      assistance, and self-care caregiver scores improved significantly more than the
      control group's scores. An intention-to-treat analysis upheld the findings and
      revealed an additional difference between the groups' BDI total score.
      CONCLUSION: The results support use of power wheelchairs with children as young
      as age 14 months to enhance development and function, although additional
      research is needed.

PMID- 22466381
TI  - Short-term, early intensive power mobility training: case report of an infant at
      risk for cerebral palsy.
AB  - PURPOSE: This case report describes the feasibility of quantifying short-term,
      intensive power mobility training for an infant soon after a diagnosis of
      cerebral palsy. KEY POINTS: An 11-month-old infant with significant mobility
      impairments and her parents were filmed during 14 consecutive daily training
      sessions. The infant moved the power chair with hand-over-hand assistance and
      performed open exploration of the joystick and toys. Mobility measures, coded
      from video, were compared across training. Frequency and combination of looking
      at and interacting with the joystick, percentage of time of moving independently,
      and average percentage of success in moving when prompted, all increased across
      the training. CLINICAL IMPLICATIONS: Quantifying short-term, intensive power
      mobility training for infants is feasible and may have yielded positive short
      term effects for this infant. The "who," "when," and "how" of early power
      mobility training, as well as the critical need for paradigm shifts in power
      mobility training, are discussed.

PMID- 22466382
TI  - Modified ride-on toy cars for early power mobility: a technical report.
AB  - BACKGROUND AND PURPOSE: Children with significantly decreased mobility have
      limited opportunities to explore their physical and social environment. A variety
      of assistive technologies are available to increase mobility; however, no single
      device provides the level of functional mobility that children developing
      typically enjoy. The purpose of this technical report is to formally introduce a
      new power mobility option--the modified ride-on toy car. KEY POINTS: This report
      will provide (a) an overview of toy car features, (b) examples of basic
      electrical and mechanical modifications, and (c) a brief clinical case. CLINICAL
      IMPLICATIONS: With creative use and customized modifications, toy cars can
      function as a "general learning environment" for use in the clinic, home, and
      school. As such, we anticipate that these cars will become a multiuse clinical
      tool to address not only mobility goals but also goals involving body function
      and structure such as posture and movement impairments.

PMID- 22466383
TI  - Bone health in children and adolescents with juvenile idiopathic arthritis and
      the influence of short-term physical exercise.
AB  - PURPOSE: To study bone mineral density (BMD) in 54 children and adolescents with
      juvenile idiopathic arthritis before and after a short-term exercise program.
      METHODS: Fifty-four children, 41 girls and 13 boys, median age 13.9 years,
      participated in a 12-week exercise program, with 33 children in an exercise
      group. The program consisted of one hundred 2-footed jumps with a rope and
      standardized muscle strength exercise. Both BMD and bone mineral content were
      assessed with dual-energy x-ray absorptiometry (DXA) and DXA Laser Calscan for
      the heel at the start and after 3 and 6 months. RESULTS: The study group had BMD
      measurements within the reference range compared with normative data with Z score
      at start. Bone mineral density values in total body, but not Z score, increased
      significantly (P = .012) in the exercise group. CONCLUSIONS: The study group had
      BMD measurements within the reference range. Twelve weeks of exercise increases
      BMD in children with juvenile idiopathic arthritis.

PMID- 22466385
TI  - The pediatric physical therapist's role in promoting and measuring participation
      in children with disabilities.
AB  - PURPOSE: The purposes of this article were to discuss participation relative to
      the International Classification of Functioning, Disability, and Health for
      Children and Youth (ICF-CY) model, evaluate 3 current pediatric participation
      measures that have been designed to assess participation, and review research
      findings relevant to participation in children and adolescents with disabilities.
      KEY POINTS: The concept of participation has been challenging to define and
      measure. Successful participation of children and adolescents with disabilities
      in daily life activities is influenced by individual, family, and environmental
      factors. Currently available tools designed to measure participation of children
      and adolescents have strengths and limitations, which should be considered when
      selecting tools for use in clinical practice. CONCLUSION: Pediatric physical
      therapists can increase participation of children and adolescents with
      disabilities by measuring and promoting meaningful outcomes in the individual,
      family, and environmental components of the ICF-CY.

PMID- 22466386
TI  - Concurrent validity and reliability of the pediatric evaluation of disability
      inventory-computer adaptive test mobility domain.
AB  - PURPOSE: To examine concurrent validity, item-specific reliability, and score
      distributions of the new Pediatric Evaluation of Disability Inventory-Computer
      Adaptive Test (PEDI-CAT) Mobility domain with the original PEDI Functional Skills
      (FS) Mobility Scale. METHODS: Thirty-five parents of children with
      neurodevelopmental disabilities completed the PEDI-CAT on a computer and the
      paper PEDI FS via interview. RESULTS: Strength of association between the PEDI
      CAT Mobility domain and PEDI FS Mobility Scale scores was good to excellent (r =
      0.82; P < .001). Intraclass correlation coefficients ranged from .3390 to 1.000,
      and agreement ranged from 60% to 100% for 8 specific items. No child had the
      minimum score on either test, whereas 9 children (26%) had a maximum score on the
      PEDI FS Mobility Scale. CONCLUSIONS: This study provides evidence for potential
      users that the concurrent validity, reliability, and score distribution for the
      PEDI-CAT Mobility domain are adequate for use with children with varied diagnoses
      and throughout the pediatric age span.

PMID- 22466388
TI  - The relationship between spasticity and muscle volume of the knee extensors in
      children with cerebral palsy.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      spasticity and muscle volume in children with cerebral palsy (CP), using
      isokinetic dynamometry and magnetic resonance imaging. METHODS: A retrospective
      sample of 8 children with diplegic CP was analyzed. One set of 10 passive knee
      flexion movements was completed at a velocity of 180 degrees  per second with
      concurrent surface electromyography of the medial hamstrings (MH) and vastus
      lateralis (VL) to assess knee extensor spasticity. Magnetic resonance imaging was
      used to measure maximum cross-sectional area and muscle volume of the quadriceps
      femoris. RESULTS: The quadriceps femoris muscle volume was positively correlated
      with MH reflex activity, VL reflex activity, MH/VL co-contraction, and peak knee
      extensor passive torque (P < .05). CONCLUSION: The present findings suggest that
      higher levels of knee extensor muscle spasticity are associated with greater
      quadriceps muscle volume in children with spastic diplegic CP.

PMID- 22466390
TI  - Clinical instructors' perspectives:  what should we be teaching in pediatrics?
AB  - PURPOSE: This study explored clinical instructors' perspectives regarding
      specific aspects of pediatric content that should be included in the curricula of
      entry-level physical therapist education programs. METHODS: This mixed methods
      sequential explanatory study was conducted using 2 groups of participants. The
      survey-only group consisted of 278 participants who anonymously completed a Web
      based survey. The mixed-data group consisted of 9 purposively selected
      participants who completed the Web-based survey and participated in a one-on-one
      qualitative interview that explored their survey responses. RESULTS: Participants
      provided recommendations pertaining to the depth and breadth of pediatric content
      in entry-level curricula. A diagram was created to depict the participants'
      perspectives on how pediatric content in the entry-level curricula should be
      structured. CONCLUSION: Clinical instructors offer valuable insights that can be
      used to guide entry-level curricular content in pediatrics. The results of this
      study may assist physical therapist faculty in preparing students for entry-level
      practice in pediatrics.

PMID- 22466392
TI  - Comparison of motor and cognitive performance in infants during the first year of
      life.
AB  - PURPOSE: To compare motor and cognitive performance in infants with typical
      development in the 1st, 2nd, 3rd, 6th, 9th, and 12th months after birth. METHODS:
      This was a repeated-measures study with unequal sample sizes in the follow-up
      periods, comprising 94 infants born at term. Infants with genetic syndromes,
      malformations, congenital infections, or hospitalized in intensive care units
      were excluded. The Bayley Scales of Infant Development II were used for
      evaluation of cognitive and motor performance. RESULTS: There were significant
      differences between motor and cognitive performance at 1, 2, and 3 months.
      However, at 6, 9, and 12 months, there was no difference between domains.
      CONCLUSION: This study suggests that during the first year, development can be
      synchronous in the 2 areas evaluated by the Bayley Scales of Infant Development
      II, especially from the sixth month of age onward.

PMID- 22466394
TI  - Effects of a plyometric training program for 3 children with neurofibromatosis
      type 1.
AB  - BACKGROUND AND PURPOSE: To evaluate the feasibility and safety of plyometric
      training and to determine the effects on motor proficiency. CASE DESCRIPTION:
      Three children with neurofibromatosis type 1, aged 5, 7, and 10 years, selected
      for representative ages, sexes, abilities, and outcomes participated in a 10-week
      plyometric training program. Outcome measures included throwing and jumping
      distance, performance on a self-selected goal, the Bruininks-Oseretsky Test of
      Motor Proficiency, Second Edition, and the Children's Assessment of Participation
      and Enjoyment. OUTCOMES: All participants safely completed the program.
      Improvements were seen in distance and consistency of throwing and jumping,
      performance on the self-selected goal, and bilateral coordination composite
      scores. Increased diversity, but not intensity of physical activity, was
      observed. DISCUSSION: A safe plyometric training program was implemented,
      resulting in gains in motor performance. It may be important to address personal
      and environmental barriers to physical activity participation to improve
      intensity of physical activity.

PMID- 22466395
TI  - Effects of constraint-induced movement therapy on gait, balance, and functional
      locomotor mobility.

PMID- 22466398
TI  - 4,4,9,9-Tetraphenyl pyrroloindolizine: a structural analogue of calix[2]pyrrole.
AB  - Synthesis, spectral and structural characterization of a pyrroloindolizine
      derivative having structural similarity with calix[2]pyrrole is described. Here,
      two pyrrole rings are connected with two meso-carbon atoms having an N,alpha
      linkage and an alpha,beta-linkage to afford the smallest analogue in the
      calixpyrrole family. Detailed NMR spectroscopic studies along with single crystal
      X-ray analysis confirm the assigned structure of the molecule.

PMID- 22466397
TI  - Protocatechuic acid attenuates lipolysaccharide-induced acute lung injury.
AB  - Protocatechuic acid (PCA) is a major metabolite of anthocyanins. It has numerous
      pharmacological effects, including anti-inflammatory, antioxidant, and
      antitumoral activities. In the present study, we investigated the in vivo
      protective effect of PCA on acute lung injury (ALI) induced by lipolysaccharide
      (LPS) in mice. We treated mice with PCA 1 h before the intratracheal (i.n.)
      administration of LPS. The pulmonary injury severity was evaluated 6 h after LPS
      administration. We found that pretreatment with a 30 mg/kg of PCA markedly
      attenuated the LPS-induced histological alterations in the lung. In addition, PCA
      inhibited the production of several inflammatory cytokines, including tumor
      necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and IL-6, at 6
      h in the bronchoalveolar lavage fluid (BALF) after LPS challenge. Furthermore,
      PCA significantly reduced the number of total cells, neutrophils, and macrophages
      in the BALF, and it significantly decreased the wet/dry weight (W/D) ratio of
      lungs and the protein concentration in the BALF. Additionally, Western blotting
      showed that PCA efficiently blunted nuclear factor-kappa B (NF-kappaB) activation
      by inhibiting the degradation and phosphorylation of IkappaBalpha, as well as the
      translocation of p65 from cytoplasm to the nucleus. In conclusion, these results
      indicate that PCA was highly effective in inhibiting acute lung injury (ALI) and
      may be a promising potential therapeutic reagent for ALI treatment. PCA may
      utilize the NF-kappaB pathway to attenuate the nonspecific pulmonary inflammation
      induced by LPS administration.

PMID- 22466399
TI  - An approach to measure electromechanical properties of atomic and molecular
      junctions.
AB  - We describe a new setup for simultaneous measurements of force and current in
      conductive nanocontacts in a liquid environment with a high sampling rate and
      resolution. A lab-built current-to-voltage converter allows measurements of the
      current over seven orders of magnitude. As examples, we studied conductances and
      mechanical forces upon formation and breaking of gold atomic contacts and of two
      molecular junctions containing 1,2-di(4-pyridyl)ethyne (M1) and 1,4-di(4
      pyridyl)buta-1,3-diyne (M2). We found that the forces required to deform or break
      gold atomic contacts depend critically on the surrounding medium. Further, they
      show non-linear behaviour in dependence of the number N of gold atoms detached.
      The electromechanical properties of the two types of molecular junctions upon
      stretching were analysed by correlating breaking forces with simultaneously
      measured junction conductances. A rather complex behaviour in a wide range of
      forces was discovered. Comparison of the current-probe atomic force microscopy
      experiments on the rupture of molecular junctions with STM-based break junction
      experiments enables the assignment of breaking forces of molecular junctions to
      the corresponding junction conductances.

PMID- 22466400
TI  - Polycyclic aromatic hydrocarbons (PAHs) in the Mediterranean Sea: atmospheric
      occurrence, deposition and decoupling with settling fluxes in the water column.
AB  - ?(30)PAH gas phase concentrations (13-86 and 22-40 ng m(-3) in the Mediterranean
      and Black Seas, respectively) dominated the atmospheric levels due to the high
      contribution of phenanthrene, dibenzothiophene and their alkylated derivates. The
      high variability of PAH atmospheric concentrations in the different sub-basins is
      due to several factors (i.e. air-mass trajectory, proximity to sources and losses
      by deposition). The ?(30)PAH atmospheric deposition (dominated by low MW PAH net
      air-water diffusive fluxes) is estimated to be ~3100 ton y(-1) (Mediterranean)
      and ~500 ton y(-1) (Black Sea). Net volatilization for certain PAHs was
      estimated. Deposition fluxes (1-2 orders of magnitude higher than reported PAH
      settling fluxes in the water column) confirm an important depletion/sink of water
      column PAH in the photic zone, especially for low MW PAHs. Degradation processes
      in the water column may be responsible for this decoupling. Conversely, high MW
      PAHs dry deposition fluxes are similar to their settling fluxes.

PMID- 22466401
TI  - Does searching for antineutrophil cytoplasmic antibodies help with the diagnosis
      of Adult-onset Still's disease?
AB  - Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of
      unknown etiology. It is a seronegative disease with multisystemic manifestations.
      One of the important laboratory findings in AOSD is negative results for
      rheumatoid factor and antinuclear antibody. Because there is no specific,
      pathognomonic test for AOSD, diagnosis is based on a set of clinical and
      laboratory criteria and exclusion of other diseases like infections,
      malignancies, and vasculitis. It is obvious that antineutrophil cytoplasmic
      antibodies (ANCAs) are specific for vasculitis; however, few studies detected
      some types of these antibodies in rheumatoid arthritis, juvenile chronic
      arthritis, and still's disease. The aim of this study was to investigate whether
      or not ANCAs exist in sera of patients with AOSD. Forty-one AOSD patients were
      enrolled in this prospective study; patients were diagnosed according to
      Yamaguchi criteria and exclusion of other diseases by at least 6-months follow
      up. Sera from all patients were tested for p-ANCA and c-ANCA by indirect
      immunofluorescence assay. Confirmatory antigenic testing for proteinase 3 (PR3)
      and myeloperoxidase (MPO) ANCA subtypes then were performed on positive sera.
      Only one patient with AOSD in this study showed low titer of MPO-ANCA in her
      sera. In a 1-year follow-up, ANCA did not predict vasculitis in this patient.
      This study suggested that patients with AOSD are mostly seronegative for ANCAs
      too. Positive ANCA appears to be an epiphenomenon and has not any association
      with vasculitis in AOSD.

PMID- 22466403
TI  - Lack of association between polymorphisms of thrombogenic genes and disease
      susceptibility in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is associated with increased mortality due to
      cardiovascular disease (CVD). Abnormalities in coagulation have been linked with
      CVD in general and RA population. The aim of our study is to determine whether
      particular single nucleotide polymorphisms thought to be involved in the
      regulation of coagulation are over-represented in patients with RA compared to
      controls. We compared the frequency of atherothrombotic polymorphisms (Factor V
      Leiden, fibrinogen G455A, prothrombin G20210A and plasminogen activator inhibitor
      4G5G) in 322 RA patients [231 females, mean age 61.5 +/- 12, median disease
      duration 10 years (IQR = 14)] with 441 local controls. No significant differences
      were observed in genotype or allele frequencies either between RA and controls or
      between the disease subgroups studied. Whereas these polymorphisms may be of
      importance at the level of individual patients, they are unlikely to be
      clinically important on a population basis.

PMID- 22466402
TI  - Hormonal parameters and sex hormone receptor gene polymorphisms in men with
      autoimmune diseases.
AB  - Autoimmune diseases (ADs) are more common in women than in men. Sex hormones may
      play a role. Sex hormone receptors (SHR) are expressed in cells of the immune
      system. We investigated the possible role of hormonal parameters and of common
      polymorphisms of the estrogen receptor alpha (ESR1), beta (ESR2), and androgen
      receptor (AR) genes in the appearance of AD in men. 277 men were studied; 125
      with >=1 AD: Hashimoto's autoimmune thyroiditis (n = 65), Graves' disease (n =
      12), SLE (n = 10), and RA (n = 38). 152 were controls. Hormonal and biochemical
      parameters were measured after discontinuation for >=1 month of any
      corticosteroid therapy. ESR1 PvuII, ESR2 AluI, and the AR (CAG)n repeats
      polymorphisms were analyzed. AD patients had higher estradiol levels (31.32 +/-
      12.10, controls 20.37 +/- 7.91 pg/ml, p < 0.001). In multivariate analysis,
      significant predictors for AD were estrogen and BMI. The allele frequency of ESR1
      PvuII and ESR2 AluI did not differ between patients and controls (AD: 47.8 %,
      37.6 %; controls 49.8 %, 39.9 %). The distribution of (CAG)n did not differ
      between groups. In AD group, shorter (CAG)n alleles were associated with younger
      age of AD onset (short: 38.52 +/- 14.8, long: 47.14 +/- 17.34 years, p = 0.048).
      Carriers of ESR1 PvuII presented less frequently >=2 AD (carriers 6.5 %, non
      carriers 25.1 %, p = 0.019); carriers of AluI had lower SHBG levels and higher
      BetaMUIota compared to non-carriers (p < 0.04). Higher estradiol may play a role
      in AD in men. Distribution of SHR gene polymorphisms is similar between patients
      and controls. Shorter AR (CAG)n repeats may predispose for younger AD onset.
      Coexistence of >=2 AD is less frequent in carriers of ESR1 PvuII. ESR2 AluI may
      adversely affect obesity parameters.

PMID- 22466404
TI  - Factors influencing sick leave episodes in Mexican workers with rheumatoid
      arthritis and its impact on working days lost.
AB  - To evaluate impact of working days lost and factors for developing sick leave
      episodes in Mexicans workers with rheumatoid arthritis (RA). A prospective cohort
      of 123 patients with RA was followed for 1 year. Factors evaluated for sick leave
      episodes included: demographics, job characteristics, comorbidity, depressive
      symptoms, and clinical/therapeutic variables. Rates of sick leave episodes,
      working days lost, and permanent work disability (PWD) were identified.
      Statistical analysis included Cox regression models estimating hazard risks (HR)
      and their 95 % confidence intervals (95% CI). Cumulative time of follow-up for
      the cohort was 43,380 days, 24 % of workers had at least one episode of sick
      leave, with a mean of working days lost per patient-year of 18.36; 4.1 %
      developed PWD. Development of sick leave in the Kaplan-Meier analysis was
      associated with: age >=40 years (p = 0.04), having a couple (p = 0.04),
      performing manual work (p = 0.03), suffering depressive symptoms (p = 0.04),
      limitations in functioning (p = 0.01), and poor global functional status >= III
      (p = 0.01). Cox regression models identified HAQ-Di >= 0.6 as the stronger
      predictor for sick leave (HR = 4.04, 95 % CI 1.41-11.58, p = 0.009) followed by
      age (HR = 1.05, 95 % CI 1.01-1.11, p = 0.04), >=4 risk factors had a HR to 9.4
      (95 % CI: 2.1-42.7) for sick leave. In this prospective cohort of Mexican workers
      with RA, we identified several factors associated with sick leave episodes and
      working days lost that should be potentially addressed by a multidisciplinary
      approach, being required to revaluate these strategies with the aim of increasing
      the work permanence of these patients.

PMID- 22466405
TI  - Hypoxia and hydrogen cyanamide induce bud-break and up-regulate hypoxic
      responsive genes (HRG) and VvFT in grapevine-buds.
AB  - It has been reported that dormancy-breaking compound hydrogen cyanamide (HC)
      stimulates the fermentative pathway and inhibits respiration in grapevine-buds,
      suggesting in this way, that a respiratory stress must be involved in the release
      of buds from dormancy. Here, we tested low-oxygen effect (hypoxia) on the bud
      break response of endodormant grapevine buds, and HC and hypoxia effects on the
      expression of hypoxic responsive genes (HRG) PYRUVATE DECARBOXYLASE (VvPDC),
      ALCOHOL DEHYDROGENASE (VvADH2), SUCROSE SYNTHASE (VvSUSY), non-symbiotic
      HEMOGLOBIN (VvnsHb), and on FLOWERING LOCUS T (VvFT), a transcription factor
      related to dormancy release in Vitis. Hypoxia as HC, induce transiently the
      expression of HRG and VvFT and hasten the sprouting of endodormant grapevine
      buds. During the first 24 h after treatment, HRG and VvFT were strongly induced
      by hypoxia, subsequently, their expressions fell, and 14 days post-treatment
      increased again above control levels. These results indicate that in the short
      term, a respiratory stress, caused either by oxygen deprivation or by inhibitors
      of respiration, induces transiently the expression of HRG and VvFT, and in the
      long-term, along with the advancement of bud-break, the expression of these genes
      move forward in treated buds, suggesting that these second induction that occurs
      just before bud-break is developmentally regulated.

PMID- 22466407
TI  - Control of enzyme reaction by a designed metal-ion-dependent alpha-helical coiled
      coil protein.
AB  - Regulation of protein function by external stimuli is a fascinating target for de
      novo design. We have constructed a peptide that assembles into a homotrimer in
      the presence of metal ions, such as Ni(2+), Cu(2+), and Zn(2+). We fused the
      peptide construct to the DNA-binding domain (DBD) of the heat shock factor from
      Saccharomyces cerevisiae, which binds tandem repeats of the heat shock element
      (HSE). However, the fusion protein bound to the natural three tandem HSEs even in
      the absence of metal ions, although mainly as the dimerized protein. Using
      "skipped" HSEs containing six additional nucleotides inserted between two
      adjacent HSEs, to prevent interactions between the DBDs, we found the fusion
      protein bound to the new DNA target in a metal-ion-dependent manner, as monitored
      by a HindIII protection assay. The fusion protein containing two metal binding
      sites in the metal-ion-controlled domain inhibited RNA transcription by T7 RNA
      polymerase in the presence of metal ions, in a template containing skipped HSEs
      downstream of the T7 promoter. The designed protein therefore regulates the
      functions of the enzyme in a metal-ion-dependent manner.

PMID- 22466406
TI  - Age-related cognitive decline: can neural stem cells help us?
AB  - Several studies suggest that an increase in adult neurogenesis has beneficial
      effects on emotional behavior and cognitive performance including learning and
      memory. The observation that aging has a negative effect on the proliferation of
      neural stem cells has prompted several laboratories to investigate new systems to
      artificially increase neurogenesis in senescent animals as a means to compensate
      for age-related cognitive decline. In this review we will discuss the systemic,
      cellular, and molecular changes induced by aging and affecting the neurogenic
      niche at the level of neural stem cell proliferation, their fate change, neuronal
      survival, and subsequent integration in the neuronal circuitry. Particular
      attention will be given to those manipulations that increase neurogenesis in the
      aged brain as a potential avenue towards therapy.

PMID- 22466408
TI  - Motor map reliability and aging: a TMS/fMRI study.
AB  - This study compared the reliability of motor maps over 3 sessions from both
      neuronavigated transcranial magnetic stimulation (TMS) and functional magnetic
      resonance imaging (fMRI) data between younger and older adults. Seven younger
      (ages 19-31) and seven older (ages 64-76) adults participated in three joint
      TMS/fMRI assessment sessions separated by 7 or 14 days. Sessions involved mapping
      of the right first dorsal interosseous muscle using single-pulse TMS immediately
      followed by block-design fMRI scanning involving volitional right-hand index
      finger to thumb oppositional squeeze. Intersession reliability of map volume,
      evaluated by intraclass correlation and Jaccard Coefficient between testing
      sessions, was more consistent for younger adults in both fMRI and TMS. A positive
      correlation was evidenced between fMRI and TMS map volumes and Jaccard
      Coefficients indicating spatial consistency across sessions between the two
      measures. Comparisons of map reliability between age groups showed that younger
      adults have more stable motor maps in both fMRI and TMS. fMRI and TMS maps show
      consistency across modalities. Future interpretation of motor maps should attempt
      to account for potential increased variability of such mapping in older age
      groups. Despite these age group differences in reliability, fMRI and TMS appear
      to offer consistent and complementary information about cortical representation
      of the first dorsal interosseous muscle.

PMID- 22466409
TI  - Reflex response and control of the human soleus and gastrocnemius muscles during
      walking and running at increasing velocity.
AB  - We measured the soleus and the gastrocnemius H-reflex modulation in seven
      subjects during walking at 4.5 km/h and during running at 8, 12 and 15 km/h. The
      recordings in the medial gastrocnemius were corrected for cross-talk from the
      soleus muscle. The gastrocnemius H-reflex was in general lower than the soleus H
      reflex. In both muscles the H-reflex increased significantly from walking to
      running but also with increasing running speed. The peak of EMG activity
      increased in both muscles with increasing speed. The V-wave of both muscles was
      absent or rather low during walking, but it increased significantly from walking
      to running with increasing running speed in the soleus but not in the medial
      gastrocnemius. In both muscles the V-wave was highest just prior to heel strike.
      It is suggested that this was due to a high firing frequency of the motoneurones
      in this phase of the movement. It is concluded that a shift towards the faster
      gastrocnemius at higher running speeds on behalf of the soleus muscle did not
      occur. The fact that the physiological cross-sectional area of the soleus is much
      larger than that of the lumped gastrocnemii is most probably the reason why the
      soleus is important also at higher running velocities.

PMID- 22466410
TI  - Do walkers follow their heads? Investigating the role of head rotation in
      locomotor control.
AB  - Eye and head rotations are normally correlated with changes in walking direction;
      however, it is unknown whether they play a causal role in the control of
      steering. The objective of the present study was to answer two questions about
      the role of head rotations in steering control when walking to a goal. First, are
      head rotations sufficient to elicit a change in walking direction? Second, are
      head rotations necessary to initiate a change in walking direction or guide
      steering to a goal? To answer these questions, participants either walked toward
      a goal located 7 m away or were cued to steer to the left or right by 37 degrees
      . On a subset of trials, participants were either cued to voluntarily turn their
      heads to the left or right, or they underwent an involuntary head perturbation
      via a head-mounted air jet. The results showed that large voluntary head turns
      (35 degrees ) yielded slight path deviations (1 degrees -2 degrees ) in the same
      or opposite direction as the head turn, depending on conditions, which have
      alternative explanations. Involuntary head rotations did not elicit path
      deviations despite comparable head rotation magnitudes. In addition, the walking
      trajectory when turning toward an eccentric goal was the same regardless of head
      orientation. Steering can thus be decoupled from head rotation during walking. We
      conclude that head rotations are neither a sufficient nor a necessary component
      of steering control, because they do not induce a turn and they are not required
      to initiate a turn or to guide the locomotor trajectory to a goal.

PMID- 22466411
TI  - Temporal depression of the soleus H-reflex during passive stretch.
AB  - Synaptic efficacy associated with muscle spindle feedback is regulated via
      depression at the Ia-motoneurone synapse. The inhibitory effects of repetitive Ia
      afferent discharge on target motoneurones of different sizes were investigated
      during a passive stretch of ankle extensors in humans. H-reflex recruitment
      curves were collected from the soleus muscle for two conditions in ten subjects.
      H-reflexes were elicited during passive stretch at latencies of 50, 100, 300, and
      500 ms after a slow (20 degrees /s) dorsiflexion about the right ankle (from 100
      to 90 degrees ). Control H-reflexes were recorded at corresponding static
      (without movement) ankle angles of 99, 98, 94, and 90 degrees  of flexion. The
      slope of the H-reflex recruitment curves (Hslp) was then calculated for both
      conditions. H-reflex values were similar for the static and passive stretch
      conditions prior to 50-100 ms, not showing the early facilitation typical of
      increased muscle spindle discharge rates. However, the H-reflex was significantly
      depressed by 300 ms and persisted through 500 ms. Furthermore, less than 300 ms
      into the stretch, there was significantly greater H-reflex depression with a
      lower stimulus intensity (20 % Mmax) versus a higher stimulus intensity (Hmax),
      though the effects begin to converge at later latencies (>300 ms). This suggests
      there is a distinct two-stage temporal process in the depression observed in the
      Ia afferent pathway for all motoneurones during a passive stretch. Additionally,
      there is not a single mechanism responsible for the depression, but rather both
      heterosynaptic presynaptic inhibition and homosynaptic post-activation depression
      are independently influencing the Ia-motoneurone pathway temporally during
      movement.

PMID- 22466412
TI  - Band engineered ternary solid solution CdSxSe1-x-sensitized mesoscopic TiO2 solar
      cells.
AB  - The optical band gap of the light absorber and the alignment of its bands with
      the underlying wide band gap metal oxide are critical for efficient light
      harvesting and charge separation in semiconductor-sensitized solar cells (SSCs).
      In practice, these two requirements are however not always fulfilled
      concomitantly in SSCs. Favourable band alignment in CdSe-sensitized TiO2 requires
      utilization of quantum sized CdSe, which causes great losses in the harvesting of
      long wavelength photons due to quantum confinement effects. In the present study,
      ternary cadmium sulfoselenide (CdSxSe1-x), which has a tunable band gap between
      those of CdSe and CdS without reducing the dimension, was proposed as a
      sensitizer for TiO2. CdSxSe1-x was successfully synthesized by alternately
      depositing CdS and CdSe layers under ambient conditions. SSCs utilizing CdSxSe1-x
      sensitized TiO2 yielded a power conversion efficiency of 4.05% under simulated
      AM1.5 100 mW cm(-2) illumination, rivalling the well-studied cascaded CdS/CdSe
      electrodes when an aqueous polysulfide solution was used as the electrolyte and
      Cu2S as the counter electrode. The findings of the present study provide an
      alternative and viable approach for optimizing the energetics of semiconductor
      sensitizers for efficient charge separation, while also maintaining good light
      harvesting. 

PMID- 22466413
TI  - Phylogeny of Celastrus L. (Celastraceae) inferred from two nuclear and three
      plastid markers.
AB  - This is the first comprehensive molecular investigation of the genus Celastrus L.
      Phylogenetic relationships within the genus were assessed based on sequences of
      two nuclear (ETS, ITS) and three plastid (psbA-trnH, rpl16 and trnL-F) regions
      using the Bayesian inference and the maximum parsimony methods. Our results show
      that Celastrus, together with Tripterygium, formed a maximal supported clade.
      Within the cluster, Celastrus is composed of a basal clade and a core Celastrus
      clade, and the latter is consisted of six subclades. Relationships among species
      are more influenced by latitude than continental distribution patterns. The
      cauline cyme and lunate seeds are distinct characters to one of the maximal
      supported subclades. Their close relationship, similar geographical pattern and
      habitat imply that C. flagellaris may be a potential invasive species threatening
      C. scandens in North America. Celastrus leiocarpus, C. oblanceifolius and C.
      rugosus are confirmed as synonyms of C. punctatus, C. aculeatus and C.
      glaucophyllus, respectively. Discordance between the molecular data and previous
      morphology-based subgeneric classifications are noted. More works are needed to
      clarify the relationship between Celastrus and Tripterygium and the species
      within Celastrus.

PMID- 22466414
TI  - EGFR mutations detection on liquid-based cytology: is microscopy still necessary?
AB  - Currently, there is a trend towards an increasing use of liquid-based cytology
      (LBC) to diagnose non-small cell lung cancer. In this study, to detect epidermal
      growth factor receptor mutations, different molecular techniques were applied to
      LBC samples with and without laser capture microdissection (LCM). In 58 LBCs, DNA
      was extracted twice. One sample was obtained directly from CytoLyt solution,
      whereas the other DNA sample was derived after slide preparation and LCM of
      Papanicolaou-stained cells. The rate of mutant cases obtained by direct
      sequencing was discordant between CytoLyt-derived (10.3%) and LCM-derived (17.2%)
      DNA. However, the same mutant rate (17.2%) was achieved on the matched samples by
      high-resolution melting analysis, fragment and TaqMan assays. Thus, LCM and
      direct sequencing may be replaced by more sensitive non-sequencing methods
      directly performed on CytoLyt-derived DNA, an easier and faster approach to
      improve epidermal growth factor receptor testing standardisation on LBCs.

PMID- 22466415
TI  - Progressive dysphagia caused by Erdheim-Chester disease.

PMID- 22466417
TI  - Influence of the accessory protein SET on M3 muscarinic receptor phosphorylation
      and G protein coupling.
AB  - The proto-oncogene and inhibitor of protein phosphatase 2A (PP2A), SET, interacts
      with the third intracellular loop of the M3 muscarinic receptor (M3-MR), and SET
      knockdown with small interfering RNA (siRNA) in Chinese hamster ovary (CHO) cells
      augments M3-MR signaling. However, the mechanism of this action of SET on
      receptor signaling has not been defined, and we initiated studies to address this
      question. Knockdown of SET by siRNA in CHO cells stably expressing the M3-MR did
      not alter agonist-induced receptor phosphorylation or receptor internalization.
      Instead, it increased the extent of receptor dephosphorylation after agonist
      removal by ~60%. In competition binding assays, SET knockdown increased high
      affinity binding of agonist in intact cells and membrane preparations.
      Glutathione transferase pull-down assays and site-directed mutagenesis revealed a
      SET binding site adjacent to and perhaps overlapping the G protein-binding site
      within the third intracellular loop of the receptor. Mutation of this region in
      the M3-MR altered receptor coupling to G protein. These data indicate that SET
      decreases M3-MR dephosphorylation and regulates receptor engagement with G
      protein, both of which may contribute to the inhibitory action of SET on M3-MR
      signaling.

PMID- 22466418
TI  - The effects of employment status and daily stressors on time spent on daily
      household chores in middle-aged and older adults.
AB  - PURPOSE OF THE STUDY: This study examines how employment status (worker vs.
      retiree) and life course influences (age, gender, and marital status) are
      associated with time spent on daily household chores. Second, this study assesses
      whether the associations between daily stressors and time spent on daily
      household chores differ as a function of employment status and life course
      influences. DESIGN AND METHODS: Men and women aged 55-74 from the National Study
      of Daily Experiences (N = 268; 133 workers and 135 retirees), a part of the
      National Survey of Midlife in the United States (MIDUS), completed telephone
      interviews regarding their daily experiences across 8 consecutive evenings.
      RESULTS: Working women spent more than double the amount of time on daily
      household chores than working men. Unmarried retirees spent the most time on
      daily household chores in comparison to their counterparts. There was a trend
      toward significance for the association between home stressors from the previous
      day and time spent on daily household chores as a function of employment and
      marital status. IMPLICATIONS: These findings highlight the importance of gender
      and marital status in the associations between employment status and time spent
      on daily household chores and the role that daily stressors, in particular home
      stressful events, have on daily household chore participation.

PMID- 22466420
TI  - A combinatorial TIR1/AFB-Aux/IAA co-receptor system for differential sensing of
      auxin.
AB  - The plant hormone auxin regulates virtually every aspect of plant growth and
      development. Auxin acts by binding the F-box protein transport inhibitor response
      1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA)
      transcriptional repressors. Here we show that efficient auxin binding requires
      assembly of an auxin co-receptor complex consisting of TIR1 and an Aux/IAA
      protein. Heterologous experiments in yeast and quantitative IAA binding assays
      using purified proteins showed that different combinations of TIR1 and Aux/IAA
      proteins form co-receptor complexes with a wide range of auxin-binding
      affinities. Auxin affinity seems to be largely determined by the Aux/IAA. As
      there are 6 TIR1/AUXIN SIGNALING F-BOX proteins (AFBs) and 29 Aux/IAA proteins in
      Arabidopsis thaliana, combinatorial interactions may result in many co-receptors
      with distinct auxin-sensing properties. We also demonstrate that the AFB5-Aux/IAA
      co-receptor selectively binds the auxinic herbicide picloram. This co-receptor
      system broadens the effective concentration range of the hormone and may
      contribute to the complexity of auxin response.

PMID- 22466421
TI  - Reversible targeting of noncatalytic cysteines with chemically tuned
      electrophiles.
AB  - Targeting noncatalytic cysteine residues with irreversible acrylamide-based
      inhibitors is a powerful approach for enhancing pharmacological potency and
      selectivity. Nevertheless, concerns about off-target modification motivate the
      development of reversible cysteine-targeting strategies. Here we show that
      electron-deficient olefins, including acrylamides, can be tuned to react with
      cysteine thiols in a rapidly reversible manner. Installation of a nitrile group
      increased the olefins' intrinsic reactivity, but, paradoxically, eliminated the
      formation of irreversible adducts. Incorporation of these electrophiles into a
      noncovalent kinase-recognition scaffold produced slowly dissociating, covalent
      inhibitors of the p90 ribosomal protein S6 kinase RSK2. A cocrystal structure
      revealed specific noncovalent interactions that stabilize the complex by
      positioning the electrophilic carbon near the targeted cysteine. Disruption of
      these interactions by protein unfolding or proteolysis promoted instantaneous
      cleavage of the covalent bond. Our results establish a chemistry-based framework
      for engineering sustained covalent inhibition without accumulating permanently
      modified proteins and peptides.

PMID- 22466422
TI  - Analysis of snail genes in the crustacean Parhyale hawaiensis: insight into snail
      gene family evolution.
AB  - The transcriptional repressor snail was first discovered in Drosophila
      melanogaster, where it initially plays a role in gastrulation and mesoderm
      formation, and later plays a role in neurogenesis. Among arthropods, this role of
      snail appears to be conserved in the insects Tribolium and Anopheles gambiae, but
      not in the chelicerates Cupiennius salei and Achaearanea tepidariorum, the
      myriapod Glomeris marginata, or the Branchiopod crustacean Daphnia magna. These
      data imply that within arthropoda, snail acquired its role in gastrulation and
      mesoderm formation in the insect lineage. However, crustaceans are a diverse
      group with several major taxa, making analysis of more crustaceans necessary to
      potentially understand the ancestral role of snail in Pancrustacea (crustaceans +
      insects) and thus in the ancestor of insects as well. To address these questions,
      we examined the snail family in the Malacostracan crustacean Parhyale hawaiensis.
      We found three snail homologs, Ph-snail1, Ph-snail2 and Ph-snail3, and one
      scratch homolog, Ph-scratch. Parhyale snail genes are expressed after
      gastrulation, during germband formation and elongation. Ph-snail1, Ph-snail2, and
      Ph-snail3 are expressed in distinct patterns in the neuroectoderm. Ph-snail1 is
      the only Parhyale snail gene expressed in the mesoderm, where its expression
      cycles in the mesodermal stem cells, called mesoteloblasts. The mesoteloblasts go
      through a series of cycles, where each cycle is composed of a migration phase and
      a division phase. Ph-snail1 is expressed during the migration phase, but not
      during the division phase. We found that as each mesoteloblast division produces
      one segment's worth of mesoderm, Ph-snail1 expression is linked to both the cell
      cycle and the segmental production of mesoderm.

PMID- 22466423
TI  - Coming apart at the seams: morphological evidence for pregnathal head capsule
      borders in adult Tribolium castaneum.
AB  - Cephalization and seamless fusion of the anterior body segments during
      development obscure the segmental boundaries of the insect head. Most of the
      visible seams are thought to reflect cuticular infolding for structural
      reinforcement rather than a merger of cuticular plate borders. Incomplete fusions
      and other modifications of the adult head found in eight Tribolium mutations
      indicate that the frontal and gular sutures likely are true sutures that mark
      borders between adjacent cuticular plates, and suggest that the anterior facial
      shelf is a composite of three independent cuticular surfaces: ocular, antennal,
      and clypeo-labral. Additionally, midline splits of the clypeo-labrum and gula,
      and membranous lesions on the lateral head capsule reveal probable borders of
      adjacent cuticular plates where visible sutures are normally absent. The anterior
      lateral lesions seen in the Lucifer mutation mark a border between ocular and
      antennal plates and appear to identify part of the postfrontal sutures. While
      revealing or clarifying possible intersegmental borders between ocular, antennal,
      and clypeo-labral plates, the various modified or unfused surfaces of the head
      neither reveal an additional acronal plate nor support the view that the clypeo
      labrum is segmentally associated with ocular cuticle.

PMID- 22466424
TI  - Single-molecule conductance determinations on HS(CH2)4O(CH2)4SH and
      HS(CH2)2O(CH2)2O(CH2)2SH, and comparison with alkanedithiols of the same length.
AB  - The acetyl-protected, thiol-terminated ethers AcS(CH(2))(4)O(CH(2))(4)SAc and
      AcS(CH(2))(2)O(CH(2))(2)O(CH(2))(2)SAc have been synthesised, and a range of
      related scanning tunnelling microscopy (STM)-based methods have been employed to
      fabricate and electrically characterise gold | single molecule | gold junctions
      involving these molecules. The single-molecule conductance values obtained are
      consistently found to be substantially higher (by a factor of 2-3) than the
      conductances of analogous alkanedithiols of similar length (HS(CH(2))(9)SH and
      HS(CH(2))(8)SH, respectively). A rationalisation of these findings is suggested,
      namely that the lone pair electrons on the oxygen atoms are substantially closer
      in energy to the Fermi energy of the gold leads than are the occupied and
      unoccupied states of methylene chains, so that the ether oxygens behave in a
      manner analogous to 'wells' in a double-tunnelling-barrier system. In agreement
      with this suggestion, the current-voltage behaviour of the monoether can be
      fitted using the Simmons approach, and the barrier height is found to be
      significantly lower than for alkanedithiols of approximately the same length.

PMID- 22466426
TI  - Psychiatry and nature.

PMID- 22466425
TI  - Laser pointer induced macular damage: case report and mini review.
AB  - To report laser pointer induced damage to retina and choroid and briefly review
      literature. A case report of a 13-year old Caucasian boy developed blurry central
      vision and central scotoma in right eye (OD). He was exposed for one minute to
      class IIIA green laser pointer of 650 nm wavelength and 5 mW power. Clinical
      examination showed a grayish lesion in foveal region. Ancillary testing revealed
      disruption of the retinal pigment epithelial (RPE) layer in foveal region and
      indocyanine green angiography demonstrated evidence of choroidal hypofluorescence
      suggestive of choroidal infarction in OD. Visual acuity improved from 20/100 to
      20/60 in one day and he was treated with tapering doses of oral prednisolone (40
      mg) for 3 weeks. Laser pointer with a power of >5 mW caused damage to RPE in the
      macula. Children should not be given laser pointers as toys especially those with
      label of danger instructions.

PMID- 22466427
TI  - [Polycystic ovary syndrome].
AB  - The Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in
      women of reproductive age with complex but interesting reproductive and metabolic
      ramifications. The effects of various endocrine-hormonal dysfunctions in
      psychiatry are well known and have been targeted by scientific study for quite
      some time. During the past few years, psychiatric research has shifted its
      interest to the cellular level. Steroids that originate in the periphery (e.g.
      ovaries), as well as those synthesized by the central nervous system
      (neurosteroids), have neuroplastic effects and interfere with almost all known
      neurotransmitter systems. Therefore steroid de-regulation that is caused by the
      PCOS is related to psychiatric symptomatology on both a pathophysiological and a
      clinical level. In medical psychiatric practice, PCOS is related to many
      disorders: bipolar disorder and its treatment, epilepsy, depression, cognitive
      disorders, sleep disorders, eating disorders, and somatoform disorders. On a
      psychological level, women suffering from PCOS may display depressive symptoms,
      anxiety, body image dissatisfaction, diminished sexual interest, and compromised
      quality of life. Therefore, we believe that it is useful for the clinical
      psychiatrist to keep in mind the psychiatric and the psychological aspects of
      PCOS, and their impact on patient diagnosis, course and treatment.

PMID- 22466428
TI  - [First-episode schizophrenia: Pharmacotherapy and psychosocial interventions].
AB  - The first episode of schizophrenia is a field of great interest from both
      clinical and research perspectives. Most clinical and psychosocial deterioration
      in schizophrenia occurs within the first 5 years of the onset of the illness,
      suggesting that this is a critical period for treatment initiation. Therefore,
      early detection and subsequent effective therapeutic intervention are vital for
      the patient, as they significantly determine the course and the long term outcome
      of the disease. Pharmacotherapy is the cornerstone of the whole therapeutic
      approach. Patients with first-episode psychosis are comparatively more treatment
      responsive than patients with multiple episodes. They need lower doses of
      antipsychotic medication but at the same time are quite sensitive to side effects
      mainly to extrapyramidal symptoms and signs. All current guidelines consider
      second generation antipsychotics as first choice drug for first episode
      schizophrenics. Data from few double blind randomized clinical trials indicate
      that the newer agents show equal or even better efficacy than the neuroleptics
      and to a certain extend fewer side effects, mainly extrapyramidal symptoms.
      Despite initial symptom reduction, achievement of full remission -particularly if
      it is defined according to strict criteria- and even more, achievement of full
      recovery remains unsatisfactory. Predictors of poor short term and long term
      outcome include male gender, low educational level, "soft" neurological signs,
      severe positive symptoms at baseline, cognitive deficits at intake, poor
      premorbid functioning especially during adolescence, prefrontal neuronal
      dysfunction, extrapyramidal symptoms and tardive dyskinesia early in treatment,
      long duration of untreated psychosis or untreated illness. Although published
      guidelines do not make definitive recommendations about the duration of
      maintenance treatment after the first episode, recent data suggest that 1 or 2
      years might not be adequate. Medication adherence is problematic in first episode
      schizophrenics even within the first six months. Poor adherence is predicted by
      male gender, younger age, poor insight after discharge, severe positive symptoms
      at baseline, alcohol and drug abuse, inadequate family involvement, lower
      occupational status, not positive relationship with the psychiatrist, bad
      admission experience and medication side effects. Adjunctive psychosocial
      interventions may be beneficial across a variety of domains and can assist with
      symptomatic and functional recovery. Cognitive-behavior therapy has shown modest
      efficacy in reducing symptoms and assisting patients in adjusting to their
      illness but has shown minimal efficacy in reducing relapse. Some reports support
      the benefits of family interventions, while there is a paucity of data evaluating
      group inter ventions. Comprehensive (i.e. multi element) treatment approaches
      show promise in reducing symptoms and hospital readmissions as well as improving
      functional outcomes. More randomized controlled trials are needed to evaluate the
      ef fectiveness of psychosocial interventions, in general, in first-episode
      psychosis patients.

PMID- 22466429
TI  - [The cost of treating schizophrenia in Greece].
AB  - The objective of this study was to estimate the direct annual cost of treating
      patients with schizophrenia in Greece in 2005. Due to the lack of quantitative
      data, information on the treatment pathway and medical resource utilization of
      patients were collected from a consensus panel of 9 psychiatrists and 5 health
      economists. For estimating the costs a bottom up approach from the National
      Health System perspective was used. The panel of experts defined three patient
      categories based on the severity of the disease and the medical setting where
      treatment is received: (a) outpatient setting, (b) ambulatory care, (c) inpatient
      setting and long-term care. The annual direct cost of treatment per patient was
      found to be 3,187 ? (2,659-4,166 ?) in the first category, 10,135 ? (7,429-13,972
      ?) in the second category and 20,782 ? (17,482-25,462 ?) in the third category.
      The total cost of treatment increased with the severity of the disease and the
      use of hospitalization. Systematic data collection on medical resource
      utilization must be established at the national level to facilitate further
      research, guide the efficient use of resources and improve the healthcare
      provision.

PMID- 22466430
TI  - [Evaluation of remission of manic symptoms after treatment with antipsychotics].
AB  - We investigated the progress of patients hospitalized with bipolar disorder I (BP
      I) at onset in manic episode, who were treated with antipsychotic drugs. The aims
      of the study were to estimate the time point shift where the patients show an
      improvement of manic symptoms and its behaviour characteristics, in relevance to
      the administered equivalent daily doses of antipsychotic drugs. The equivalent
      dose between antipsychotic drugs was converted with reference to risperidone. 42
      manic patients (males=13, mean age=41.6 years) with BP-I were treated daily with
      conventional and atypical antipsychotics, and evaluated in severity of manic
      symptoms and their cognitive and behavioural characteristics using Young' Mania
      Rating Scale. Evaluation of manic symptoms was taking place weekly during
      hospitalisation in Psychiatric Adult Section Clinic of General Hospital. Manic
      symptomatology showed a statistical decrease (P<0.001) from baseline to the
      fourth (and lasted up to the eighth) week of hospitalisation in the 76% of
      patients, with this decrement to reflect the decline of mean total score in YMRS
      from 39.3 to 29 and to 23.3, respectively. Increasing the mean equivalent
      antipsychotic dose to 9.3 mg daily (SD+/-1.3) there was a decrement in manic
      symptomatology with change to occur at about third week of treatment. We discuss
      the findings either with reference to the point of remission of manic symptoms.

PMID- 22466431
TI  - [The role of serotonergic 2C receptors in neurobiology and treatment of eating
      disorders].
AB  - Biological vulnerability concerning eating disorders can include dysfunction of
      neurotransmitters such as serotonin, dopamine and norepinephrine that regulate
      feeding. Studies have shown that all three neurotransmitters, especially
      serotonergic system, are dysfunctional in eating disorders. Although the satiety
      promoting role of the serotonergic system in the control of food intake is well
      established, there is no current evidence that any selective serotonergic
      receptor subtype mediates the intake of a specific macronutrient. The role of 5
      HT1A and 5-HT2C receptor subtypes on food intake and dietary choices was
      investigated. 20 groups of male Wistar rats, 8 animals each, were intraperitoneal
      injected 0.05-4.0 mg/kg buspirone (5-HT1A agonist), 1.0 and 3.0 mg/kg mesulergine
      (5-HT2C antagonist with dopaminergic properties), 5.0 and 10.0 mg/kg m
      chlorophenylpiperazine (m-CPP) (5-HT2C/1B agonist) and combinations of
      mesulergine with buspirone or m-CPP, as well as buspirone with m-CPP at same
      doses. One group of rats received 1.0 mg/kg apomorphine (dopamine agonist).
      Animals were given access to a pair of isocaloric diets (protein, PED, or
      carbohydrate enriched diet, CED) for 4 hours after drug treatment in a food
      deprivation schedule. Mesulergine caused hyperphagia accompanied by an increase
      in both PED and CED intake, with CED intake reversed by m-CPP. Busprirone and m
      CPP spared protein intake, with an increase and decrease of CED intake
      consequently. Buspirone due to its action on 5-HT1A autoreceptors seems to affect
      diet selection indirectly, since its effect on carbohydrate intake is reversed by
      m-CPP. 5-HT2C receptor blockade seems to be the most significant reason for
      increased carbohydrate consumption, rather than the inhibition of serotonin (5
      HT) release through the 5-HT1A receptors. Our results suggest that both 5-HT1A
      and 5-HT2C receptor subtypes are involved in the protein-sparing effect of 5-HT,
      while the 5-HT2C receptors may have the prominent role on 5-HT induced food and
      carbohydrate intake suppression. These findings extend our understanding on
      neurobiological substrate of appetite and contribute to the studies related to
      new drugs against hyperphagia and other eating disorders, especially those
      referred to 5-HT2C compounds with agonistic properties.

PMID- 22466432
TI  - [Psychiatric hospital and the progrees of psychiatric reform].
AB  - Two decades have already passed since the onset of psychiatric reform in our
      country. In the following article, we discuss the course and evolution of
      psychiatric reform. We refer to the inherent weaknesses of the original design,
      which did not monitor the status of psychiatric services in order to permit
      evaluation of the course of psychiatric reform. We present the problems that have
      emerged in the newly created psychiatric facilities and services, and we propose
      that monitoring system of the psychiatric reform should be established as soon as
      possible, while the goals should be reformulated in order to endorse accumulated
      experience. We specifically claim that psychiatric hospitals should not be closed
      entirely, and that their further reduction should follow the creation of a better
      organized system of outpatient psychiatric facilities. Finally, we refer to the
      need for a floor, where colleagues will be free to debate the process of
      psychiatric reform.

PMID- 22466433
TI  - Laser desorption ionization mass spectrometric imaging of mass barcoded gold
      nanoparticles for security applications.
AB  - Patterns created by the inkjet printing of functionalized gold nanoparticles
      (NPs) can be selectively detected by laser desorption/ionization imaging mass
      spectrometry (LDI-IMS). These patterns can only be visualized by mass, providing
      a robust yet tunable system for potential anti-counterfeiting applications.

PMID- 22466434
TI  - Multi-faceted case management: reducing compensation costs of musculoskeletal
      work injuries in Australia.
AB  - OBJECTIVES: This study aimed to determine whether a multi-faceted model of
      management of work related musculoskeletal disorders reduced compensation claim
      costs and days of compensation for injured workers. METHODS: An intervention
      including early reporting, employee centred case management and removal of
      barriers to return to work was instituted in 16 selected companies with a
      combined remuneration over $337 million. Outcomes were evaluated by an
      administrative dataset from the Victorian WorkCover Authority database. A 'quasi
      experimental' pre-post design was employed with 492 matched companies without the
      intervention used as a control group and an average of 21 months of post
      intervention follow-up. Primary outcomes were average number of days of
      compensation and average cost of claims. Secondary outcomes were total medical
      costs and weekly benefits paid. RESULTS: Information on 3,312 claims was
      analysed. In companies where the intervention was introduced the average cost of
      claims was reduced from $6,019 to $3,913 (estimated difference $2,329, 95 % CI
      $1,318-$3,340) and the number of days of compensation decreased from 33.5 to 14.1
      (HR 0.77, 95 % CI 0.67-0.88). Medical costs and weekly benefits costs were also
      lower after the intervention (p < 0.05). Reduction in claims costs were noted
      across industry types, injury location and most employer sizes. CONCLUSIONS: The
      model of claims management investigated was effective in reducing the number of
      days of compensation, total claim costs, total medical costs and the amount paid
      in weekly benefits. Further research should investigate whether the intervention
      improves non-financial outcomes in the return to work process.

PMID- 22466436
TI  - Standardization of traditional Chinese medicine and evaluation of evidence from
      its clinical practice.
AB  - Traditional Chinese medicine (TCM) is a typical traditional medicine (TM) with a
      long-standing history of preventing and curing diseases in China and other
      countries in East Asia. Standardization of TCM has been a topic of discussion
      over the past few decades in China with the goal of promoting advances in TCM in
      China and elsewhere around the world. Many quality and safety control standards
      for TCMs have been implemented in China, but systematic standards of efficacy
      have not been established for TCMs until now because of the absence of evidence
      from clinical practice. Evidence-based medicine (EBM) is the best way to provide
      evidence from clinical practice, but the quality of current EBM studies of TCM,
      and especially randomized controlled trials (RCTs) of TCM, needs to be improved.
      International registration of clinical trials (CTs) of TCM is a good way to
      provide quality evidence from clinical practice of TCM because it can improve
      research transparency and ultimately enhance the validity and value of scientific
      evidence. This evidence will provide the springboard for efforts to standardize
      TCM.

PMID- 22466435
TI  - Gender differences in personal and work-related determinants of return-to-work
      following long-term disability: a 5-year cohort study.
AB  - OBJECTIVE: To assess the differential effect of personal and work-related
      psychosocial, physical and organizational determinants by gender on time to
      return-to-work (RTW) following long-term disability. METHODS: Data come from a
      larger study conducted in the province of Quebec, Canada. A cohort of 455 adults
      on long-term disability due to work-related musculoskeletal disorders at the
      back/neck/upper limb was followed for 5 years through structured interviews and
      administrative databases. Left-truncated Cox regression modeling stratified by
      gender was used to assess time to a first partial or full RTW of at least 3 days.
      RESULTS: Survival curves of time to RTW were similar between men and women on
      long-term disability (log-rank test p value = 0.920) but many personal and
      occupational factors influencing RTW differed by gender. Women's risk factors
      included older age (HR = 0.734--in 10 years unit), poor to very poor perceived
      economic status (HR = 0.625), working >=40 h/week and having dependents (HR =
      0.508) and awareness of workplace-based occupational health and safety program
      (HR = 0.598); higher gross annual income (in $10,000 s) was a facilitator (HR =
      1.225). In men, being over 55 years old (HR = 0.458), poor perceived economic
      status (HR = 0.653), working >=40 h/week and high perceived physical workload (HR
      = 0.720) and higher job insecurity (HR = 0.825) negatively influenced time to
      RTW. For both men and women, probabilities of not returning to work varied widely
      according to workers' specific profile of personal and occupational factors (high
      or low risk profile). CONCLUSION: Results confirm the importance of gender
      sensitive strategies to investigate RTW determinants from a gender perspective.

PMID- 22466437
TI  - Effective neurofibromatosis therapeutics blocking the oncogenic kinase PAK1.
AB  - Neurofibromatosis (NF) is a family of genetic diseases which are caused by
      dysfunction of either NF1 gene or NF2 gene. One in 3,000 people suffer from this
      tumor-carrying NF. NF1 gene product is a RAS GTPase activating protein (GAP) of
      2,818 amino acids, which normally attenuates the GTP-dependent signal transducing
      activity of the G protein RAS. Dysfunction of this GAP leads to the abnormal
      activation of RAS, and eventually an oncogenic kinase called PAK1 as well. NF2
      gene product is ''Merlin'' which directly inactivates PAK1. Thus, dysfunction of
      Merlin causes the abnormal activation of PAK1. In other words, dysfunction of NF1
      gene (causing type 1 NF) is basically the same as dysfunction of NF2 gene
      (causing type 2 NF). In fact the growth of both NF1 and NF2 tumors requires PAK1,
      and all PAK1 blockers, synthetic chemicals or natural products, suppress the
      growth of these NF tumor cells both in vitro (cell culture) and in vivo (mice).  
      However, until recently, no FDA-approved effective NF therapeutics is available
      on the market. Here a series of anti-PAK1 products shall be introduced, which
      would be potentially useful for the life-long treatment of NF patients in the
      future. These include the most potent HDAC (histone deacetylase) inhibitor FK228
      (IC<sub>50</sub>: around 1 nM), that eventually blocks PAK1, the direct PAK1
      inhibitor PF3758309 (IC<sub>50</sub>: around 10 nM), a CAPE (caffeic acid
      phenethyl ester)-based propolis extract called ''Bio 30'' from NZ (New Zealand),
      and an ARC (artepillin C)-based green propolis extract (GPE) from Brazil.
      Although the first two drugs are potent, none of them is available on the market
      as yet. The last two natural (bee-made) products are available on the market, and
      have been used for the therapy of NF and tuberous sclerosis (TSC) as well as many
      PAK1-dependent solid cancers such as breast and pancreatic cancers as well as
      glioma, which altogether represent more than 70% of all human cancers. Since PAK1
      is not essential for the normal cell growth, propolis extracts cause no side
      effects.

PMID- 22466438
TI  - Synthesis and anti-HIV activity of novel 2,4-disubstituted-7-methyl-1,1,3-trioxo
      2H,4H-pyrazolo[4,5-e][1,2,4]thiadiazine derivatives.
AB  - A series of novel 2,4-disubstituted-7-methyl-1,1,3-trioxo-2H,4H-pyrazolo[4,5
      e][1,2,4]thiadiazines (PTDs) was prepared starting from a ring of pyrazolo[4,5
      e][1,2,4]thiadiazine nuclei with two different alkyl halides obtained by a facile
      one-pot reaction. The structures of all synthesized compounds were confirmed by
      <sup>1</sup>H- and <sup>13</sup>C-NMR, infrared spectra (IR), and mass spectra
      (MS) spectroscopic analysis. Anti-HIV activity was evaluated and none of the
      compounds were found to inhibit HIV replication in human T-lymphocyte (MT-4) cell
      culture.

PMID- 22466439
TI  - A new cell-based reporter system for sensitive screening of nuclear export
      inhibitors.
AB  - Nucleocytoplasmic transport of proteins across the nuclear pore complex (NPC),
      mediated by the nuclear localization signal (NLS) and the nuclear export signal
      (NES), is a vital homeostatic process in eukaryotic cells and also in mitogen
      activated protein kinase (MEK) signaling molecule in tumor cell proliferation.
      Some viruses, including the influenza virus and HIV-1, also employ this nuclear
      export mechanism during their life cycle. Hence, drugs that control
      nucleocytoplasmic transport of proteins are putative candidate antivirals or anti
      cancer agents. Thus, we previously developed a GFP/NES-MDCK reporter cell system
      for screening novel nuclear export inhibitors. NES signal-conjugated GFP
      accumulates in the nucleus in the presence of the nuclear export inhibitor
      leptomycin B (LMB). In this study, a stable GFP/NLS/NES fusion protein-expressing
      cell line was established, and its potential as a reporter was evaluated. The
      GFP/NLS/NES-MDCK cell line demonstrates improved nuclear accumulation of GFP in a
      time-course treatment with LMB. In addition, the dose-response data demonstrated
      superior sensitivity of GFP/NLS/NES-MDCK over GFP/NES-MDCK cells. As low as 0.01
      ng/mL LMB is sufficient to cause accumulation of the GFP fusion protein in the
      nucleus in GFP/NLS/NES-MDCK cells, while at least 1 ng/mL of LMB is needed for
      the accumulation of GFP fusion protein in the nucleus of GFP/NES-MDCK cells.
      These results indicate that the newly established GFP/NLS/NES-MDCK cell line is a
      potentially powerful tool to screen for novel nuclear export inhibitors.

PMID- 22466440
TI  - Levels of effectiveness of gene therapies targeting survivin and its splice
      variants in human breast cancer cells.
AB  - In order to develop an effective strategy of breast cancer therapy targeting
      survivin and its splice variants survivin-DeltaEx3 and survivin-2B, the present
      study constructed four expression vectors by fusing the survivin antisense gene,
      the survivin (T34A) gene, the survivin-DeltaEx3 antisense gene, and the survivin
      2B gene with the enhanced green fluorescent protein (eGFP) gene. Each of these
      vectors was transiently transfected into the B-Cap-37 human breast cancer cell
      line. The effects of these four vectors with diverse genes on the proliferation
      and apoptosis of B-Cap-37 breast cancer cells were examined and compared in vitro
      using MTT and flow cytometry assays. Results of the MTT assay indicated that all
      four gene therapy plasmids were most effective at inhibiting the proliferation of
      B-Cap-37 cells 72 h after transfection. However, the four gene therapies had
      different rates of cell inhibition. pcDNA3.1(+)-egfp-anti-survivin and
      pcDNA3.1(+)-survivin (T34A)-egfp had almost equivalent or better effectiveness at
      suppressing cell growth. pcDNA3.1(+)-egfp-anti-survivin-DeltaEx3 moderately
      inhibited the growth of B-Cap-37 cells. In contrast, pcDNA3.1(+)-survivin-2B-egfp
      had limited inhibition of cell growth. Similar profile of effectiveness of four
      gene therapies in soliciting cell apoptosis was also observed. These results
      suggest the relative importance of targeting survivin and its splice variant
      survivin-DeltaEx3 in breast cancer treatment.

PMID- 22466441
TI  - Ferulic acid induces heme oxygenase-1 via activation of ERK and Nrf2.
AB  - This study investigated the effect of ferulic acid (FA) on the up-regulation of
      heme oxygenase-1 (HO-1) in lymphocytes and the molecular mechanisms involved.
      Lymphocytes were treated with FA (0.001-0.1 MUM) for certain times. Cell
      viability, the activity and level of expression of HO-1, and signal pathways were
      analyzed. FA significantly upregulated HO-1 expression both at the level of mRNA
      and protein in lymphocytes. Moreover, FA induced NF-E2-related factor (Nrf2)
      nuclear translocation and transcriptional activity, which is upstream of FA
      induced HO-1 expression. In addition, lymphocytes treated with FA exhibited
      activation of extracellular regulated kinase (ERK) and treatments with U0126 (an
      ERK kinase inhibitor) attenuated the FA induced activation of Nrf2, resulting in
      a decrease in HO-1 expression. Zinc protoporphyrin (ZnPP, a HO-1 inhibitor)
      markedly suppressed cytoprotection from radiation-induced cell damage by FA.
      Results suggested that the ERK signaling pathway controlled the anti-oxidation of
      FA by regulating the expression of the antioxidant enzyme HO-1.

PMID- 22466442
TI  - In vitro bactericidal activity against periodontopathic bacteria by electrolyzed
      ion-reduced water.
AB  - As typical periodontopathic bacteria, Porphyromonas gingivalis (P. gingivalis)
      and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) were exposed
      to electrolyzed ion-reduced water (ERI) and ERI containing 1% sodium
      carboxymethylcellulose (CMC-Na) (ERI-1% CMC-Na), and the time course of their
      bactericidal action was evaluated. More than 99% of each bacteria species were
      killed after exposure to each solution for 15 sec. In addition, 1% CMC-Na, which
      was added to prolong bactericidal action, did not affect the bactericidal action
      of ERI. Its bactericidal action was concentration-dependent. No viable P.
      gingivalis bacteria were observed at a concentration of 15% of the undiluted
      solution and no viable A. actinomycetemcomitans bacteria were observed at a
      concentration of 50%, indicating differences in the bactericidal action of ERI
      for the two bacteria species. These results suggest that ERI may be extremely
      useful in preventing and treating periodontal diseases.

PMID- 22466443
TI  - Preparation and evaluation of fenoterol hydrobromide suppositories.
AB  - Fenoterol HBr is a bronchodilator known to be subject to first pass effect after
      oral administration. The aim of this study was to prepare and evaluate fenoterol
      HBr suppositories. Suppositories were prepared by a fusion method using different
      fatty bases, viz. Witepsol H15, Witepsol E75, Suppocire AP, and Suppocire BM, as
      well as different hydrophilic bases, viz. polyethylene glycol and poloxamer
      bases. In vitro release studies revealed a greater release of the drug from
      hydrophilic bases than from fatty bases. The effect of incorporating different
      types and concentrations of non-ionic surfactants (Tween 60 and Span 20) on the
      release rate of the drug from Witepsol H15, as a model fatty base, was
      investigated. Results showed an enhanced release at low surfactant
      concentrations. A very fast 100% drug release was achieved when the drug was
      incorporated as an aqueous solution in Witepsol H15 (F17). This formula was
      selected to test the effect of fenoterol HBr suppositories on histamine-induced
      bronchospasms in Guinea pigs. No dyspnea of the animals was recorded for up to 30
      min. In addition, thermogel liquid suppositories of different poloxamer 188 and
      poloxamer 407 proportions in the presence of sodium alginate as a mucoadhesive
      polymer were prepared. The different formulations behaved similarly concerning
      sustainment of drug release, however, only the formula containing 15% poloxamer
      188 and 25% poloxamer 407 (F20) showed optimal gelation at body temperature. In
      conclusion, among the studied suppository bases there are bases suitable for fast
      release of the drug like F17 and hydrophilic bases especially polyethylene
      glycol, as well as other bases for sustained release applications of fenoterol
      HBr like fatty and thermogel bases.

PMID- 22466444
TI  - Effectiveness of Teriparatide in women over 75 years of age with severe
      osteoporosis: 36-month results from the European Forsteo Observational Study
      (EFOS).
AB  - This predefined analysis of the European Forsteo Observational Study (EFOS) aimed
      to describe clinical fracture incidence, back pain, and health-related quality of
      life (HRQoL) during 18 months of teriparatide treatment and 18 months post
      teriparatide in the subgroup of 589 postmenopausal women with osteoporosis aged
      >=75 years. Data on clinical fractures, back pain (visual analogue scale, VAS),
      and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in
      6-month intervals and analyzed using logistic regression with repeated measures.
      A repeated-measures model analyzed changes from baseline in back pain VAS and EQ
      VAS. During the 36-month observation period, 87 (14.8 %) women aged >=75 years
      sustained a total of 111 new fractures: 37 (33.3 %) vertebral fractures and 74
      (66.7 %) nonvertebral fractures. Adjusted odds of fracture was decreased by 80 %
      in the 30 to <36-month interval compared with the first 6-month interval (P <
      0.009). Although the older subgroup had higher back pain scores and poorer HRQoL
      at baseline than the younger subgroup, both age groups showed significant
      reductions in back pain and improvements in HRQoL postbaseline. In conclusion,
      women aged >=75 years with severe postmenopausal osteoporosis treated with
      teriparatide in normal clinical practice showed a reduced clinical fracture
      incidence by 30 months compared with baseline. An improvement in HRQoL and,
      possibly, an early and significant reduction in back pain were also observed,
      which lasted for at least 18 months after teriparatide discontinuation when
      patients were taking other osteoporosis medication. The results should be
      interpreted in the context of an uncontrolled observational study.

PMID- 22466445
TI  - The effect of level and downhill running on cortical and trabecular bone in
      growing rats.
AB  - Mechanical loading is essential for bone development and prevention of age
      related bone diseases. Muscular contractions during physical activity and the
      generated strain magnitude are primary determinants for the osteogenic response.
      However, the adaptation capacity of bones, especially due to different muscle
      contraction types, is largely unknown. In the present study we examined the
      effect of different running modes characterized by different muscle contraction
      types and loading patterns on the morphological, structural, and mechanical
      properties of different sites in the femur of growing rats. Thirty-six female
      Sprague-Dawley rats were randomly assigned to a nonactive age-matched control
      (AMC), a level running (LEVEL), and a 20 degrees  decline downhill running (DOWN)
      group (n = 12 each). Running groups were trained on a treadmill for 30 min/day, 5
      days/week for 6 weeks. After death, pQCT analysis of the meta- and diaphyses,
      micro-CT analysis of the epiphysis, and mechanical testing of the femur were
      performed. The Tb.BMD in the metaphysis was significantly (P < 0.05) increased in
      the DOWN compared to the AMC group, whereas level running had no effect on
      Tb.BMD. While Young's modulus was significantly different (P < 0.05) between the
      DOWN and LEVEL groups, no structural alterations were found in the diaphysis
      between the groups. Further, subchondral trabecular bone did not show exercise
      induced changes caused by the different running modes but displayed a remarkably
      high intraepiphyseal variability. Downhill running seems to be a potent
      osteogenic stimulus in the femoral metaphysis.

PMID- 22466446
TI  - Asymmetric alpha-oxyacylation of cyclic ketones.
AB  - Reaction of cyclic ketones with chiral N-alkyl-O-acyl hydroxylamines leads to the
      corresponding alpha-oxyacylated carbonyl compound in up to 89% ee. The levels of
      asymmetric induction were influenced by solvent polarity, acid strength and, to a
      lesser extent, temperature. Increasing the steric bulk around the nitrogen atom
      of the hydroxylamine reagent led to increased levels of asymmetric induction,
      which was also found to be detrimental to the yield observed for the
      transformation. Examination of N- and O-substituents along with substrates
      revealed the scope and limitations of the procedure.

PMID- 22466447
TI  - Identification and functional study of a new FLO10-derivative gene from the
      industrial flocculating yeast SPSC01.
AB  - Yeast flocculation is an important property for the brewing industry as well as
      for ethanol fermentation to facilitate biomass recovery by sedimentation from the
      fermentation broth, which is cost-effective. In this study, a new flocculating
      gene FLO10 (spsc) of 4,221 bp homologous to FLO10 was identified in the
      industrial flocculating yeast SPSC01. Sequence analysis indicated that the N- and
      C-terminus of the deduced protein of this new FLO gene are 99 % identical to that
      of FLO10, but more intragenic repeats are included. The study on the function of
      FLO10 (spsc) by its integrative expression in the non-flocculating industrial
      yeast indicated severe inhibition in the flocculation of the transformant by
      mannose and maltose, moderate inhibition by sucrose and glucose and no inhibition
      by xylose and galactose, and thus the NewFlo type was established. Meanwhile, the
      flocculation of the transformant was stable when the temperature was below 50 
      degrees C and the pH was in the range of 4.0-6.0. Furthermore, the medium
      containing 250 g/l glucose was completely fermented within 48 h by the
      transformant, with about 110 g/l ethanol and 5.5 g(DCW)/l biomass produced, and
      no significant difference in ethanol fermentation performance was observed
      compared to its wide-type strain. Therefore, the FLO gene and corresponding
      transformation strategy provide a platform for engineering yeast strains with the
      flocculation phenotype to facilitate biomass recovery.

PMID- 22466448
TI  - The longitudinal relationship between emotion awareness and internalising
      symptoms during late childhood.
AB  - Emotion awareness, the ability to reflect upon the own emotions, is assumed to
      contribute to better mental health. However, empirical support for this
      relationship has only been cross-sectional. In this study we examined the extent
      to which individual differences in changes in emotion awareness over time can
      explain individual differences in changes in symptoms of internalising problems
      (depression, fear, worrying and ruminative thoughts). Children and young
      teenagers (368 boys and 295 girls) were asked four times to fill out self-report
      questionnaires, with a 6-month time interval between each time. The mean age was
      10 years during the first data collection. Longitudinal multilevel analyses
      showed that the variance in emotion awareness trends was highly predictive for
      the variance in trends for internalizing problems over time. The ability to
      differentiate discrete emotions was a strong predictor and negatively contributed
      to all internalising symptoms. In addition, a diminished tendency to address and
      value emotions contributed to more depressive symptoms; whereas hiding the own
      emotions contributed to more worrying and ruminative thoughts. The outcomes show
      that individual differences in emotion awareness over time make a strong, and,
      above all, negative contribution to the prediction of the individual differences
      in various internalizing symptoms. The fact that several aspects of emotional
      (dys)functioning are uniquely related to different kinds of internalizing
      problems gives valuable and useful information not only theoretically but also
      clinically about the distinctive nature of these problems.

PMID- 22466449
TI  - Nanosecond time-resolved IR study of thiobenzoylnitrene.
AB  - Nanosecond time-resolved infrared (TRIR) spectroscopy has been used to observe
      singlet thiobenzoylnitrene at 1740 cm(-1) upon photolysis of 5-phenyl-1,2,3,4
      thiatriazole in acetonitrile and dichloromethane. Consistent with the
      experimental observations, thiobenzoylnitrene is predicted by B3LYP/6-31G*
      calculations to have a singlet ground state with an intense IR band at 1752 cm(
      1). Phenyl isothiocyanate is also produced. Kinetic measurements indicate that it
      is not formed from singlet thiobenzoylnitrene, but rather directly from the
      thiatriazole. Unlike benzoylnitrene, singlet thiobenzoylnitrene does not react
      with acetonitrile or dichloromethane on the nanosecond timescale. However, it
      does react with dimethyl sulfoxide (DMSO) to produce a sulfoximine detected at
      1180 cm(-1) (k(DMSO) = 3 * 10(5) M(-1) s(-1)). Benzonitrile (observed at 2230 cm(
      1)) is produced from both singlet thiobenzoylnitrene (presumably through a short
      lived, unobservable benzonitrile sulfide intermediate) and directly from the
      thiatriazole. B3LYP/6-31G* calculations also show that the structure of singlet
      thiobenzoylnitrene is analogous to that of related acylnitrenes, with a
      significant bonding interaction between the nitrogen and sulfur. Triplet
      thiobenzoylnitrene, on the other hand, is predicted computationally to have a
      biradical structure.

PMID- 22466450
TI  - Calmodulin-binding protein CBP60g is a positive regulator of both disease
      resistance and drought tolerance in Arabidopsis.
AB  - Calmodulin-binding proteins (CBPs) have been known to be involved in both biotic
      and abiotic stress responses. Recently, two closely related CBPs, Arabidopsis SAR
      Deficient 1 and CBP60g, were found to belong to a new family of transcription
      factors that regulate salicylic acid (SA) biosynthesis triggered by microbe
      associated molecular patterns. In this study, we found that overexpression of
      CBP60g in Arabidopsis caused elevated SA accumulation, increased expression of
      the defense genes, and enhanced resistance to Pseudomonas syringae. In addition
      to the enhanced defense response, the CBP60g overexpression lines showed
      hypersensitivity to abscisic acid (ABA) and enhanced tolerance to drought stress.
      We also found that treatment with ABA and drought stress leads to a higher
      expression level of the ICS1 gene, which encodes isochorismate synthase, in the
      CBP60g overexpression lines than in the wild-type control plants. Our results
      suggest that CBP60g serves as a molecular link that positively regulates ABA- and
      SA-mediated pathways in plants. KEY MESSAGE: Overexpression of CBP60g in
      Arabidopsis enhanced the defense response, hypersensitivity to abscisic acid and
      tolerance to drought stress.

PMID- 22466452
TI  - Site-specific methylation in gene coding region underlies transcriptional
      silencing of the Phytochrome A epiallele in Arabidopsis thaliana.
AB  - DNA methylation in cytosine residues plays an important role in regulating gene
      expression. Densely methylated transgenes are often silenced. In contrast,
      several eukaryotic genomes express moderately methylated genes. These
      methylations are found in the CG context within the coding region (gene body).
      The role of gene body methylation in gene expression, however, is not clear. The
      Arabidopsis Phytochrome A epiallele, phyA', carries hypermethylation in several
      CG sites resident to the coding region. As a result, phyA' is transcriptionally
      silenced and confers strong mutant phenotype. Mutations in chromatin modification
      factors and RNAi genes failed to revert the mutant phenotype, suggesting the
      involvement of a distinct epigenetic mechanism associated with phyA' silencing.
      Using the forward genetics approach, a suppressor line, termed as suppressor of p
      hyA' silencing 1 (sps1), was isolated. Genetic and molecular analysis revealed
      that sps1 mutation reactivates the phyA' locus without altering its methylation
      density. However, hypomethylation at a specific CG site in exon 1 was
      consistently associated with the release of phyA' silencing. While gene
      underlying sps1 mutation is yet to be identified, microarray analysis suggested
      that its targets are the expressed genes or euchromatic loci in Arabidopsis
      genome. By identifying the association of phyA' silencing with the methylation of
      a specific CG site in exon 1, the present work shows that site-specific
      methylation confers greater effect on transcription than the methylation density
      within gene-body. Further, as the identified site (exon 1) is not critical for
      the promoter activity, transcription elongation rather than transcription
      initiation is likely to be affected by this site-specific CG methylation.

PMID- 22466454
TI  - Epigenetic bystander-like effects of stroke in somatic organs.
AB  - Clinical evidence suggests that stroke may lead to damage of somatic organs. This
      communication of damage is well- established in the case of exposure to genotoxic
      agents is termed a bystander effect. Genotoxic stress-induced bystander effects
      are epigenetically mediated. Here we investigated whether stroke causes
      epigenetic bystander-like effects in the liver, kidney and heart. We found a
      significant increase in the levels of H3K3 acetylation and H3K4 trimethylation,
      as well as a decrease in the H3K9 trimethylation in the kidney tissue of stroked
      rats. Furthermore, here we for the first time show changes in the gene and
      microRNA expression profile in the kidney tissues of stroked rats, as compared to
      intact control animals. Interestingly, the observed changes were somewhat similar
      to those reported earlier in kidney injury, inflammation, and acute renal
      failure. Our data explain the recent epidemiological evidence for the increased
      incidence of acute kidney injury post-stroke and provide an important roadmap for
      the future analysis of the mechanisms and cellular repercussions of the stroke
      induced bystander-like effects in distal somatic organs.

PMID- 22466455
TI  - Vestibular inputs modulate somatosensory cortical processing.
AB  - The vestibular system is unique among the senses because of the entirely
      multisensory nature of its cortical projections. Neuroanatomical and neuroimaging
      studies show that vestibular stimulation activates somatosensory areas, and
      particularly the so-called parieto-insular vestibular cortex (PIVC) in the
      monkey, while deactivating visual areas. Further, recent psychophysical studies
      showed that vestibular stimulation facilitates detection of electrocutaneous
      stimuli, suggesting a vestibular-somatosensory perceptual interaction. However,
      the functional mechanism underlying this perceptual facilitation remains unclear.
      We therefore recorded somatosensory potentials evoked by left median nerve
      stimulation, before and immediately after left cold caloric vestibular
      stimulation (CVS), in a small-scale study of eight healthy volunteers. CVS
      selectively enhanced the N80 component recorded over both ipsilateral and
      contralateral somatosensory areas, without significantly affecting earlier or
      later components. Interestingly, the N80 component has been localised to the
      parietal operculum, which includes the human homologue of the monkey PIVC, and is
      thus a prime neuroanatomical candidate for vestibular-somatosensory convergence.
      As a control, we measured visual evoked potentials to reversing checkerboard
      patterns and found no effects of vestibular stimulation. This rules out
      explanations based on indirect effects of vestibular modulations, such as general
      arousal or supramodal spatial attention. We believe our results provide the first
      clue linking brain structure to function for the interaction between vestibular
      and somatosensory systems.

PMID- 22466456
TI  - Metal atomic contact under electrochemical potential control.
AB  - Electric conductance of the metal atomic contacts of Au and Pd was investigated
      using a scanning tunneling microscope (STM) in solution under electrochemical
      potential control. At the hydrogen evolution potential, a fractional conductance
      peak appeared around 0.5 G(0) (G(0) = 2e(2)/h) in the conductance histograms of
      Au contacts. For Pd contacts, peaks appeared around 1.0 G(0) in the conductance
      histograms at the hydrogen evolution potential. The conductance behavior and
      atomic configuration of the metal atomic contacts at hydrogen evolution potential
      were discussed based on previously reported experimental results and theoretical
      calculation results. We have proposed the formation of hydrogen adsorbed metal Au
      and Pd contacts in solution at the hydrogen evolution potential.

PMID- 22466457
TI  - Clinical characteristics of occult macular dystrophy in family with mutation of
      RP1l1 gene.
AB  - PURPOSE: To report the clinical characteristics of occult macular dystrophy (OMD)
      in members of one family with a mutation of the RP1L1 gene. METHODS: Fourteen
      members with a p.Arg45Trp mutation in the RP1L1 gene were examined. The visual
      acuity, visual fields, fundus photographs, fluorescein angiograms, full-field
      electroretinograms, multifocal electroretinograms, and optical coherence
      tomographic images were examined. The clinical symptoms and signs and course of
      the disease were documented. RESULTS: All the members with the RP1L1 mutation
      except one woman had ocular symptoms and signs of OMD. The fundus was normal in
      all the patients during the entire follow-up period except in one patient with
      diabetic retinopathy. Optical coherence tomography detected the early morphologic
      abnormalities both in the photoreceptor inner/outer segment line and cone outer
      segment tip line. However, the multifocal electroretinograms were more reliable
      in detecting minimal macular dysfunction at an early stage of OMD. CONCLUSION:
      The abnormalities in the multifocal electroretinograms and optical coherence
      tomography observed in the OMD patients of different durations strongly support
      the contribution of RP1L1 mutation to the presence of this disease.

PMID- 22466458
TI  - Choroidal thickness in inferior staphyloma associated with posterior serous
      retinal detachment.
AB  - PURPOSE: The purpose of the study was to describe the choroidal findings in eyes
      with posterior serous retinal detachment associated with inferior staphyloma by
      enhanced depth imaging optical coherence tomography. METHODS: The study involved
      five eyes of five patients with the inferior staphyloma accompanied by posterior
      serous retinal detachment. In each case, the upper border of the staphyloma was
      lying across the macula. Enhanced depth imaging spectral domain optical coherence
      tomography was performed in a vertical-sectional manner through the fovea, and
      the choroidal thicknesses at the thinnest point, at the fovea, and at 0.5 mm and
      1.0 mm superior and inferior to the thinnest point were measured. Fluorescein
      angiography and indocyanine green angiography were also performed. RESULTS: In
      all 5 eyes, the choroid was thinnest at the upper border of the staphyloma (mean,
      37.4 MUm; SD, 13.5 MUm; range, 23-53 MUm). Fluorescein angiography showed a band
      of window defects along the upper border of the staphyloma, where indocyanine
      green angiography demonstrated persistent hypoperfusion in all 5 eyes.
      CONCLUSION: The choroid was markedly thin at the upper border of the inferior
      staphyloma accompanied by posterior serous retinal detachment. Such choroidal
      abnormality seemed to play an important role in the development of serous retinal
      detachment.

PMID- 22466459
TI  - En face spectral-domain optical coherence tomography outer retinal analysis and
      relation to visual acuity.
AB  - PURPOSE: To describe a method of en face visualization and quantification of the
      photoreceptor inner segment/outer segment junction area, using spectral-domain
      optical coherence tomography, and association with visual acuity. METHODS: Case
      series of 74 eyes in 53 patients. Central 1-mm and 400-MUm en face areas were
      analyzed with a computer algorithm. RESULTS: The presence or absence of inner
      segment/outer segment junction was visible on both spectral-domain optical
      coherence tomography en face and retinal cross sections. Thirty eyes (40.6%) had
      no retinal pathology and an average logMAR visual acuity of 0.116. Twenty-five
      eyes (33.8%) had intraretinal edema, with visual acuity of 0.494. Nineteen eyes
      had nonneovascular age-related macular degeneration (dry age-related macular
      degeneration, 25.6%), with visual acuity of 0.392. In all eyes, central 1-mm and
      400-MUm en face areas were 58.3 +/- 25.0% and 56.4 +/- 26.0%, which showed
      significant correlation with visual acuity (Pearson correlation, r = -0.66 and 
      0.56, both P < 0.001). This correlation was greater than correlation of visual
      acuity with central subfield thickness (r = 0.39, P < 0.001), macular volume (r =
      0.36, P = 0.002), and average macular thickness (r = 0.37, P = 0.001). However,
      no variables were significantly correlated with dry age-related macular
      degeneration eyes. CONCLUSION: Central en face inner segment/outer segment
      junction areas are significantly correlated with visual acuity in most eyes. This
      may correlate better with visual acuity than other spectral-domain optical
      coherence tomography values, as a reflection of photoreceptor integrity. Dry age
      related macular degeneration may disrupt the plane used to formulate the en face
      display. Advancements in spectral-domain optical coherence tomography may provide
      routine en face visualization analysis.

PMID- 22466460
TI  - The rationale of retinal endovascular fibrinolysis in the treatment of retinal
      vein occlusion: from experimental data to clinical application.
AB  - PURPOSE: We describe a retinal endovascular fibrinolysis technique to directly
      reperfuse experimentally occluded retinal veins using a simple micropipette.
      METHODS: Retinal vein occlusion was photochemically induced in 12 eyes of 12
      minipigs: after intravenous injection of 10% fluorescein (1-mL bolus), the
      targeted retinal vein segment was exposed to thrombin (50 units) and to Argon
      laser (100-200 mW) through a pars plana approach. A beveled micropipette with a
      30-MUm-diameter sharp edge was used for micropuncture of the occluded vein and
      endovascular microinjection of tissue plasminogen activator (50 MUg/mL) in 11
      eyes. In one control eye, balanced salt solution was injected. The lesion site
      was examined histologically. RESULTS: Retinal vein occlusion was achieved in all
      cases. Endovascular microinjection of tissue plasminogen activator or balanced
      salt solution led to reperfusion of the occluded retinal vein in all cases.
      Indicative of successful reperfusion were the following: continuous endovascular
      flow, unaffected collateral circulation, no optic disk ischemia, and no venous
      wall bleeding. However, balanced salt solution injection was accompanied by
      thrombus formation at the punctured site, whereas no thrombus was observed with
      tissue plasminogen activator injection. CONCLUSION: Retinal endovascular
      fibrinolysis constitutes an efficient method of micropuncture and reperfusion of
      an experimentally occluded retinal vein. Thrombus formation at the punctured site
      can be prevented by injection of tissue plasminogen activator.

PMID- 22466461
TI  - The effect of fellow eye visual acuity on visual acuity of study eyes receiving
      ranibizumab for age-related macular degeneration.
AB  - PURPOSE: To investigate whether extremes in visual acuity (very good or very
      poor) of the fellow eye (FE) influence visual acuity of the study eye in patients
      receiving intravitreal ranibizumab treatment for neovascular age-related macular
      degeneration. METHODS: From 2 randomized, controlled, clinical trials (MARINA and
      ANCHOR), we performed a retrospective analysis of ranibizumab-treated patients
      who maintained stable FE visual acuity (+/-5 letters from baseline at each of
      Months 1, 4, 6, and 12), comparing patients with untreated FE visual acuity that
      was either 20/32 or better (very good) or 20/200 or worse (very poor). Visual
      acuity of the treated study eyes, which received monthly intravitreal ranibizumab
      (0.3 mg or 0.5 mg), was compared between the 2 FE cohorts at the Month 6 and
      Month 12 visits. RESULTS: A total of 145 patients were analyzed. In the cohort
      with very poor FE visual acuity (n = 55), there were 35 patients in MARINA and 20
      patients in ANCHOR; in the cohort with very good FE visual acuity (n = 90), there
      were 52 patients in MARINA and 38 patients in ANCHOR.The mean (standard
      deviation) gain of the study eye visual acuity in the very good FE cohort was
      10.3 (13.3) and 10.8 (13.7) letters at Months 6 and 12, respectively, compared
      with a lesser mean visual acuity gain of 4.6 (12.2) and 6.7 (11.7) letters at
      Months 6 and 12 in the very poor vision FE cohort. There was no statistically
      significant difference (adjusted) in the study eye visual acuity change between
      the 2 cohorts at either 6 months (P = 0.11) or 12 months (P = 0.26). CONCLUSION:
      This retrospective analysis of the MARINA and ANCHOR study data did not support
      the hypothesis that FE visual acuity plays a significant role in driving visual
      acuity of patients receiving monthly intravitreal ranibizumab injections for
      neovascular age-related macular degeneration. Visual acuity of the FE by itself
      is, therefore, not a useful parameter in predicting visual acuity in a majority
      of ranibizumab-treated patients.

PMID- 22466462
TI  - Comparative analysis of macular microstructure by spectral-domain optical
      coherence tomography before and after silicone oil removal.
AB  - PURPOSE: To document comparative analysis of macular microstructures before and
      after silicone oil (SO) removal via spectral-domain optical coherence tomography
      and to assess the retinal changes associated with visual outcome. METHODS: Forty
      six eyes that underwent vitrectomy with SO tamponade were included. Ophthalmic
      examinations were performed before SO removal and at Months 1, 3, and 6
      postoperatively including best-corrected visual acuity and spectral-domain
      optical coherence tomography. The macular microstructures identified by spectral
      domain optical coherence tomography were compared before and after SO removal,
      and tomographic parameters related to visual outcome were analyzed. RESULTS:
      Under SO tamponade, spectral-domain optical coherence tomography demonstrated
      macular tomographic findings: epiretinal membrane in 12 eyes (26.1%), cystoid
      macular edema in 9 (19.6%), undulated inner retina in 8 (17.4%), and submacular
      fluid in 4 (8.7%). The mean duration of SO tamponade was significantly longer in
      eyes with macular changes (6.3 +/- 4.6 months) than those without changes (5.2 +/
      4.4 months) (P = 0.02). A total of 13 eyes had peeling of epiretinal membrane or
      internal limiting membrane combined with SO removal. After SO removal, most of
      microstructural changes were resolved. In the eyes with macular epiretinal
      membrane or cystoid macular edema, final best-corrected visual acuity was
      significantly improved compared with baseline (P = 0.017, 0.049), which
      paralleled the decrease of central foveal thickness. Restoration of photoreceptor
      layer and external limiting membrane was achieved in 2 (4.9%) and 5 eyes (12.5%),
      and those with continuous photoreceptor layer or external limiting membrane had
      the better final best-corrected visual acuity. CONCLUSION: Under SO tamponade,
      macular microstructural changes were identified by spectral-domain optical
      coherence tomography and were associated with duration of SO tamponade. Most of
      the microstructural changes were recovered after SO removal, if needed, combined
      with macular surgery. Anatomic resolution was accompanied by postoperative visual
      improvement.

PMID- 22466464
TI  - 23-gauge pediatric vitrectomy using limbus-based trocar-cannulas.

PMID- 22466463
TI  - Pattern dystrophy with high intrafamilial variability associated with Y141C
      mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV
      related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal
      injections.
AB  - OBJECTIVE: To identify disease causing mutation in three generations of a Swiss
      family with pattern dystrophy and high intrafamilial variability of phenotype. To
      assess the effect of intravitreal ranibizumab injections in the treatment of
      subfoveal choroidal neovascularization associated with pattern dystrophy in one
      patient. METHODS: Affected family members were ascertained for phenotypic and
      genotypic characterization. Ophthalmic evaluations included fundus photography,
      autofluorescence imaging, optical coherence tomography, and International Society
      for Clinical Electrophysiology of Vision standard full-field electroretinography.
      When possible family members had genetic testing. The proband presented with
      choroidal neovascularization and had intravitreal injections as needed according
      to visual acuity and optical coherence tomography. RESULTS: Proband had a
      multifocal type pattern dystrophy, and his choroidal neovascularization regressed
      after four intravitreal injections. The vision improved from 0.8 to 1.0, and
      optical coherence tomography showed complete anatomical restoration. A butterfly
      shaped pattern was observed in her cousin, whereas a fundus pulverulentus pattern
      was seen in a second cousin. Aunt had a multifocal atrophic appearance,
      simulating geographic atrophy in age-related macular degeneration. The Y141C
      mutation was identified in the peripherin/RDS gene and segregated with disease in
      the family. CONCLUSION: This is the first report of marked intrafamilial
      variation of pattern dystrophy because of peripherin/RDS Y141C mutation.
      Intravitreal ranibizumab injections might be a valuable treatment for associated
      subfoveal choroidal neovascularization.

PMID- 22466465
TI  - A lack of delayed intraocular pressure elevation in patients treated with
      intravitreal injection of bevacizumab and ranibizumab.
AB  - PURPOSE: The purpose of this study was to report the rate of intraocular pressure
      (IOP) elevation after intravitreal injections of anti-vascular endothelial growth
      factor agents for exudative age-related macular degeneration. METHODS:
      Retrospective chart review of all patients receiving intravitreal ranibizumab
      and/or bevacizumab injections for exudative age-related macular degeneration from
      November 2005 to June 2010. Delayed ocular hypertension (OHT) was defined as
      either an IOP >=22 mmHg on 2 consecutive visits (with an increase from baseline
      >6 mmHg) or an IOP >26 mmHg on a single visit with a concomitant initiation or
      augmentation of IOP-lowering treatment. Noninjected fellow eyes served as
      controls. Incidence of delayed OHT was analyzed using survival analyses, with
      risk assessed by Cox proportional hazards regression models. Eyes with glaucoma
      were evaluated separately. RESULTS: Three hundred and two treated eyes and 226
      control eyes met inclusion criteria. In eyes with exudative age-related macular
      degeneration without glaucoma, 3 of 270 injected eyes (0.51% incidence per eye
      year) developed delayed OHT compared with 4 of 195 control eyes (1.00% incidence
      per eye-year), a difference that was not statistically significant (hazard ratio
      = 0.48; 95% confidence interval: 0.11-2.23). In eyes with exudative age-related
      macular degeneration and glaucoma, 2 of 32 injected eyes developed delayed OHT
      (3.1% incidence per eye-year) compared with 3 of 31 control eyes (5.7% incidence
      per eye-year), a difference that was not statistically significant (hazard ratio
      = 0.59; 95% confidence interval: 0.10-3.60). CONCLUSION: The incidence of delayed
      OHT after intravitreal anti-vascular endothelial growth factor injections was low
      and did not differ between injected and control eyes, including eyes with
      glaucoma. These results argue against a significant risk of IOP elevation because
      of repeated anti-vascular endothelial growth factor therapy.

PMID- 22466466
TI  - Choroidal thickness and visual acuity in highly myopic eyes.
AB  - PURPOSE: To examine predictive factors for visual acuity in highly myopic eyes.
      METHODS: Consecutive patients with high myopia (>=6 diopters [D]) with no other
      pathology such as lacquer cracks in the fovea, choroidal neovascularization, or
      myopic macular schisis, were evaluated. The study was performed in 2 retina
      centers, one in the United States and the other in Japan. Enhanced depth imaging
      optical coherence tomography was obtained, and the central foveal, outer retinal
      hyporeflective layer and inner segment to retinal pigment epithelium aggregate,
      and the subfoveal choroidal thicknesses were measured. Correlations were
      calculated among the measured variables and visual acuity. Generalized estimating
      equation models were used to identify predictors of visual acuity. RESULTS: The
      New York cohort was composed of 35 eyes of 25 patients who had a mean age of 57
      years (standard deviation, +/-18.1 years) and a mean refractive error of -10.9 D
      (+/-3.6 D). The Japanese cohort was composed of 110 eyes of 61 patients who had a
      mean age of 46.8 years (+/-14.7 years) and a mean refractive error of -9.2 D (+/
      3.1 D) and a mean axial length of 27 mm (+/-1.4 mm). The mean subfoveal choroidal
      thickness was 113.3 MUm (+/-53.9 MUm) in the New York group and 172.9 MUm (+/
      72.8 MUm) in the Japanese group. In each group, the subfoveal choroidal thickness
      showed a significant inverse correlation with age and myopic refractive spherical
      equivalent. The subfoveal choroidal thickness was inversely correlated with
      logarithm of the minimum angle of resolution visual acuity (P = 0.041, New York
      group; P = 0.001, Japan group). The only significant predictor in the pooled data
      for logarithm of the minimum angle of resolution visual acuity was subfoveal
      choroidal thickness (P <= 0.001). Clinic location was not a significant
      predictor. CONCLUSION: Choroidal thickness in high myopia is inversely correlated
      with increasing age and myopic refractive error and is an important predictor of
      visual acuity. Given that myopia is increasing worldwide, these findings may have
      epidemiologic significance.

PMID- 22466467
TI  - Preemptive analgesia with ropivacaine for pars plana vitrectomy: randomized
      controlled trial on efficacy and required dose.
AB  - BACKGROUND: The rationale of preemptive analgesia in ocular surgery is avoiding
      central sensitization because of nociceptive stimuli. The applicability in
      clinical practice has been argued because evidence for a relevant effect is
      missing. The present study attempts to demonstrate a clinically relevant pain
      reduction by preemptive peribulbar ropivacaine injection. METHODS: Sixty patients
      scheduled for vitrectomy under general anesthesia between March and June 2007
      were randomly assigned to receive 0.75% ropivacaine with 75 IU of hyaluronidase
      as peribulbar injection of 1, 3, or 5 mL before or 5 mL after surgery. Control
      subjects were 30 patients without any additional analgesic treatment. Groups were
      compared regarding procedure duration, consumed amount of analgesics during and
      after surgery, and pain 1, 3, and 24 hours postoperatively. RESULTS:
      Postoperative pain was most marked in control subjects and in the group that
      received the injection after surgery. Before surgery, the dose of 5 mL of
      ropivacaine was most effective (postoperative pain median = 0), whereas patients
      who had received 1 mL or 3 mL reported some pain. CONCLUSION: The study
      highlights the benefit of the concept of preemptive analgesia in general: the
      peribulbar injection of 5 mL of 0.75% ropivacaine before surgery provides a
      substantial benefit in terms of analgesic demand and postoperative discomfort.

PMID- 22466468
TI  - Spectral domain optical coherence tomography classification of acute posterior
      multifocal placoid pigment epitheliopathy.
AB  - PURPOSE: To study the retinal morphologic changes occurring in acute posterior
      multifocal placoid pigment epitheliopathy using spectral domain optical coherence
      tomography. METHODS: Prospective observational case series of 12 eyes (6
      consecutive patients) diagnosed with acute posterior multifocal placoid pigment
      epitheliopathy. All patients underwent complete ophthalmologic examination,
      fundus photography, fluorescein angiography, and spectral domain optical
      coherence tomography at the initial visit. During follow-up, ophthalmologic
      examination and spectral domain optical coherence tomography scans were
      performed. The scans were directed to the lesions observed on the clinical
      examination and fluorescein angiography. RESULTS: Spectral domain optical
      coherence tomography classification containing four distinct stages for acute
      posterior multifocal placoid pigment epitheliopathy is proposed. Stage 1
      demonstrates a dome-shaped elevation with disruption of the photoreceptor
      junction that flattens shortly after. Stage 2, occurring 2 weeks later,
      demonstrates distinct separation between the photoreceptor junction and the
      retinal pigment epithelium (RPE). Stage 3, visible 6 weeks post disease
      initiation, demonstrates accentuated RPE hyperreflectivity and union of the RPE
      and photoreceptor junction. Stage 4, the resolution phase, starts at 3 months
      demonstrating reformation of 2 distinct visible layers of photoreceptors and RPE.
      CONCLUSION: The morphologic retinal findings in acute posterior multifocal
      placoid pigment epitheliopathy visible by the spectral domain optical coherence
      tomography occur in the outer retina, mainly the photoreceptors and RPE. Most
      findings reached nearly complete resolution and were correlated with improvement
      in visual acuity.

PMID- 22466469
TI  - Long-term results of intravitreal ranibizumab, intravitreal ranibizumab with
      photodynamic therapy, and intravitreal triamcinolone with photodynamic therapy
      for the treatment of retinal angiomatous proliferation.
AB  - PURPOSE: To compare intravitreal ranibizumab, intravitreal ranibizumab plus
      photodynamic therapy (PDT), and intravitreal triamcinolone plus PDT in retinal
      angiomatous proliferation, presenting the results of a 3-year follow-up. METHODS:
      Thirty-seven eyes of 37 patients with retinal angiomatous proliferation were
      randomized to 1 of the 3 groups. Group 1 (n = 13) received 3 monthly injections
      of 0.5 mg ranibizumab, Group 2 (n = 13) received 1 session of PDT and 3 monthly
      injections of ranibizumab, and Group 3 (n = 11) received 1 session of PDT and 1
      injection of 4 mg triamcinolone. Retreatment, with the same therapeutic scheme in
      each group, was considered in case of persistence or recurrence of
      subretinal/intraretinal fluid. RESULTS: Twelve patients in Groups 1 and 2 and 9
      patients in Group 3 completed the 3-year follow-up. A total of 58% of patients in
      Group 1, 50% in Group 2, and 88.9% in Group 3 had the same or better visual
      acuity at the end of the follow-up (P = 0.081). Patients in Group 3 exhibited
      considerable improvement in visual acuity (P = 0.032) and statistically
      significant decrease in central retinal thickness (P < 0.0001) than the 2 other
      groups at the end of the follow-up. Also, the patients in Group 3 received on
      average the lowest number of injections (P < 0.0001). Of note, geographic atrophy
      mainly at the place of previous retinal angiomatous proliferation lesion was
      detected in 0% in Group 1, 25% in Group 2, and 55.6% in Group 3 (P = 0.203),
      while 33.3% of patients in Group 1 developed retinal scar. CONCLUSION: Treatment
      with ranibizumab or ranibizumab plus PDT resulted in stabilization of the
      disease, while treatment with IVT plus PDT achieved better results in terms of
      functional and anatomical features compared with the other groups.

PMID- 22466470
TI  - Foveal cavitation as an optical coherence tomography finding in central cone
      dysfunction.
AB  - PURPOSE: To describe a distinctive foveal cavitation as seen by spectral-domain
      optical coherence tomography in certain cone dysfunction syndromes. METHODS:
      Observational case series. Patients were evaluated by dilated fundus examination,
      fundus photography, fundus autofluorescence, full-field electroretinogram,
      multifocal electroretinogram, spectral-domain optical coherence tomography, color
      vision testing, fluorescein angiography, Goldmann visual field testing, and
      molecular genetic analysis. RESULTS: We present eight patients with foveal
      cavitation in association with presumed cone dysfunction. This was characterized
      on spectral-domain optical coherence tomography by a gap in the subfoveal outer
      segment layer without more diffuse retinal thinning. There were 5 patients of age
      10 years to 27 years and 3 patients of age 49 years to 52 years, with a 1.5- to
      38-year history of bilateral visual loss. A small foveal oval-shaped area of
      reduced foveal fundus autofluorescence, surrounded by increased fundus
      autofluorescence, was seen in the younger patients, and a broad circle of
      increased fundus autofluorescence in the older patients. The multifocal
      electroretinogram always showed central amplitude reduction, but there were
      varying degrees of cone dysfunction on full-field electroretinogram. There were
      mild abnormalities on desaturated color vision testing. The family history was
      noncontributory in all cases. None of the cases were congenital. ABCA4 gene
      mutations were identified in three of five patients tested; CNGB3 testing was
      negative in these patients. CONCLUSION: Cone dysfunction syndromes typically show
      retinal thinning on optical coherence tomography imaging, although several case
      reports have noted focal outer retinal loss. Our case series shows that a
      distinctive optical coherence tomography finding, foveal cavitation, may be a
      clue to cone dysfunction syndromes, but is not specific to any one hereditary
      disorder or age group.

PMID- 22466471
TI  - Endodiathermy plus photocoagulation as treatment of sclerotomy site
      vascularization secondary to pars plana vitrectomy for proliferative diabetic
      retinopathy.
AB  - PURPOSE: To evaluate the results of surgery with pars plana vitrectomy (PPV),
      endodiathermy of sclerotomy site fibrovascularization and adjuvant
      photocoagulation of the peripheral retina to the pars plana as treatment of
      recurrent vitreous hemorrhage secondary to PPV for proliferative diabetic
      retinopathy (PDR). METHODS: Tertiary care center, Barraquer Center of
      Ophthalmology, Barcelona, Spain. Prospective interventional study of 14 eyes of
      14 consecutive patients aged 20 years to 47 years with recurrent vitreous
      hemorrhage because of sclerotomy site neovascularization secondary to PPV for
      PDR. All patients were treated by cataract, or transparent lens, extraction with
      intraocular lens implantation plus 20-gauge PPV of the vitreous base, including
      incarcerated vitreous of the sclerotomy site, together with endodiathermy of
      sclerotomy site fibrovascular tissue and adjuvant photocoagulation to the pars
      plana. Preoperative evaluation was performed by 20-MHz, high-resolution, anterior
      segment ultrasonography of the neovascularized sclerotomy sites, pre- and
      postoperative visual acuity (logarithm of the minimum angle of resolution), and
      postoperative rebleeding rates. RESULTS: Recurrent vitreous hemorrhage appeared 8
      +/- 4 months after the initial PPV for PDR. Ten (71%) patients had isolated
      vascularization of a single sclerotomy site and 4 (29%) had vascularization of 2
      sclerotomy sites. Nine of the 18 vascularized sites (50%) corresponded to optical
      fiber sclerotomies, 7 (39%) to vitreotome, and 2 (11%) to infusion sclerotomies.
      All the neovascularized sclerotomies presented sentinel vessels in the anterior
      segment. No patient showed postoperative recurrent vitreous hemorrhage during
      follow-up of 23 +/- 10 months; all showed improved visual acuity, from initial
      2.23 (+/-1.13 standard deviation) to final 0.23 (+/-0.09 standard deviation).
      CONCLUSION: According to our study, the technique of choice for the treatment of
      recurrent vitreous hemorrhage secondary to PPV for PDR is endodiathermy of
      sclerotomy site fibrovascularization and adjuvant photocoagulation of the
      peripheral retina to the pars plana. This technique treats the etiology of the
      problem, improves final best-corrected visual acuity, and, most importantly,
      helps prevent recurrent bleeding.

PMID- 22466472
TI  - Changes in ciliary body thickness in patients with diabetic macular edema after
      vitrectomy.
AB  - PURPOSE: The purpose of the study to determine whether ciliary body thickness
      increased in the presence of diabetic macular edema (DME) and whether it changed
      after pars plana vitrectomy. METHODS: A DME group consisted of 26 diabetic
      patients who underwent pars plana vitrectomy for diffuse DME. An epiretinal
      membrane group, a surgical control group, consisted of 23 nondiabetic patients
      with epiretinal membrane who underwent pars plana vitrectomy. A healthy control
      was also included for the comparison of preoperative ciliary body thickness.
      Ciliary body thickness was measured using ultrasound biomicroscopy, and central
      macular thickness was determined using optical coherence tomography. The visual
      acuity, ciliary body thickness, and central macular thickness were compared
      between groups before and 1, 2, and 4 months after pars plana vitrectomy, and the
      correlations between the central macular thickness and ciliary body thickness and
      best-corrected visual acuity were determined. RESULTS: The preoperative ciliary
      body thickness was increased significantly in the DME group compared with the
      epiretinal membrane and healthy control groups (both P < 0.001). The ciliary body
      thickness decreased significantly 1 and 2 months after surgery in the DME group
      (both P < 0.001) but not in the epiretinal membrane group. In the DME group, the
      postvitrectomy changes in the ciliary body thickness and central macular
      thickness showed similar trends and persisted significantly, until 4 months
      postoperatively (P = 0.027 and P = 0.010, respectively). The correlations between
      the preoperative central macular thickness and ciliary body thickness and between
      changes in central macular thickness and ciliary body thickness before and 2
      months after surgery were not significant. CONCLUSION: Ciliary body thickness was
      increased in patients with DME, and vitrectomy was effective in decreasing
      ciliary body edema as well as macular edema in those patients during the 4-month
      follow-up period.

PMID- 22466473
TI  - Plus disease in retinopathy of prematurity: diagnostic impact of field of view.
AB  - PURPOSE: To examine the impact of retinal field of view and magnification on
      interexpert reliability of plus disease diagnosis in retinopathy of prematurity.
      METHODS: Fifteen wide-angle images from infants with retinopathy of prematurity
      were cropped and adjusted in magnification to create 2 additional image
      categories: medium angle (40 degrees -50 degrees ) and narrow angle (20 degrees 
      30 degrees ). These 45 images were uploaded to a Web-based system and interpreted
      independently by 13 experts of retinopathy of prematurity using a 3-level (plus,
      preplus, neither) and 2-level (plus, not plus) classification. Absolute agreement
      and kappa statistics were calculated to compare interexpert reliability. RESULTS:
      In the 3-level classification, >= 70% experts agreed on the same diagnosis in 8
      of the 15 wide-angle images (53%), but only in 3 of the 15 medium-angle (20%) and
      3 of the 15 narrow-angle (20%) images. In the 2-level classification, >= 80%
      experts agreed on the same diagnosis in 11 of the 15 wide-angle images (73%), but
      only in 9 of the 15 medium-angle (60%) and 3 of the 15 narrow-angle (20%) images.
      Mean kappa of each expert compared with all other experts was 0.40 to 0.59 in 8
      of 13 experts (62%) using wide-angle images, was 0 to 0.19 in 7 of 13 experts
      (54%) using medium-angle images, and was 0.20 to 0.39 in 9 of 13 experts (69%)
      using narrow-angle images. CONCLUSION: Interexpert agreement in plus disease
      diagnosis in wide-angle images is higher than from medium-angle and narrow-angle
      images. Plus disease is defined using a narrow-angle standard published
      photograph, yet this study suggests that peripheral findings also contribute to
      diagnosis.

PMID- 22466474
TI  - Snoring is associated with unexpected patient head movement during monitored
      anesthesia care vitreoretinal surgery.
AB  - PURPOSE: To assess whether snoring is associated with sudden patient movement
      during local anesthesia with intravenous sedation. METHODS: In this prospective
      cohort study, patients undergoing ocular surgery with local anesthesia with
      intravenous sedation were studied. The occurrence or absence of snoring, and
      whether patient movement was noted were prospectively recorded. Complications
      that arose from patient movement were also noted. RESULTS: A total of 230
      surgical procedures were included in the study. All cases were vitreoretinal
      surgery cases. During 37 procedures, snoring was noted, and among these, 18
      patients (48.6%) moved their head suddenly. In contrast, movement occurred during
      only 2 of 193 procedures (1.0%) without documented snoring (P < 0.001). Thus,
      sudden patient head movement was approximately 49 times more prevalent in
      patients who snored. Continuous infusion propofol was also associated with sudden
      unexpected head movement (P = 0.0028). No complications as a result of the
      movement were identified in this study. CONCLUSION: Snoring during local
      anesthesia with intravenous sedation predicts a high likelihood of sudden patient
      movement during local anesthesia with intravenous sedation. The use of continuous
      infusion propofol anesthetic may increase the chance of head movement. Eye
      surgeons should be aware of these associations to help minimize the risk of
      complications caused by patient movement.

PMID- 22466475
TI  - Diplopia was not predictable and not associated with buckle position after
      scleral buckling surgery for retinal detachment.
AB  - PURPOSE: The possibility of postoperative binocular diplopia is seen as an
      important drawback of conventional scleral buckling surgery for rhegmatogenous
      retinal detachment. The goal of this study was to evaluate the occurrence and
      pattern of binocular diplopia after scleral buckle procedures in patients with
      rhegmatogenous retinal detachment. METHODS: In a retrospective study of 1,030
      patients with primary rhegmatogenous retinal detachment who were treated by
      scleral buckle surgery between January 2001 and July 2008, the postoperative
      occurrence of binocular diplopia was retrieved from the medical charts. RESULTS:
      Secondary strabismus developed in 39 subjects (3.8%) after scleral buckle surgery
      during a mean follow-up of 6.4 +/- 6.3 months. Twenty-eight patients (2.7%)
      developed strabismus because of a mechanical restriction of one of the muscles.
      No association was found between the position of the buckle, that is, the muscle
      affected, and the incidence of diplopia. A moderate significant association was
      found when two muscles were affected with a higher incidence of diplopia. This
      was, however, not found for three or more muscles. In 28 of 39 patients,
      binocular single vision was restored at the end of the follow-up period. In the
      majority, this was accomplished with conventional prism treatment. CONCLUSION:
      Strabismus caused by a restriction of the muscles in scleral buckle surgery was
      not predictable based upon the buckle position. Patients with a minimal
      restriction of the muscles after scleral buckle surgery can often be well treated
      with prisms.

PMID- 22466476
TI  - Combined fluorescein angiography and spectral-domain optical coherence tomography
      imaging of classic choroidal neovascularization secondary to age-related macular
      degeneration before and after intravitreal ranibizumab injections.
AB  - PURPOSE: To evaluate the combined fluorescein angiography and spectral-domain
      optical coherence tomography features in a consecutive series of exudative age
      related macular degeneration eyes with classic choroidal neovascularization
      before and after anti-vascular endothelial growth factor treatment. METHODS:
      Retrospective interventional study. All consecutive patients with exudative age
      related macular degeneration because of newly diagnosed classic choroidal
      neovascularization visited during 3 months and treated by intravitreal
      ranibizumab injection on "as-needed" basis were analyzed. Combined fluorescein
      angiography and spectral-domain optical coherence tomography examination
      (Spectralis Heidelberg Retina Angiograph OCT) was performed at baseline and at
      the 12-month follow-up visit. RESULTS: Twenty-nine treatment-naive eyes (29
      patients, 10 men and 19 women, mean age 76.28 +/- 10.86 years) were included. A
      mean of 5.3 +/- 3.5 injections was administered during 12 months. At Month 12
      visit, patients showed an improved best-corrected visual acuity (P = 0.01), a
      reduction of linear dimension of the entire lesion on fluorescein angiography (P
      = 0.02), and a reduction of the entire lesion width on spectral-domain optical
      coherence tomography (P < 0.001). At baseline, in all cases we distinguished on
      spectral-domain optical coherence tomography scan a highly reflective subretinal
      lesion, above and separate from the retinal pigment epithelium. The highly
      reflective subretinal lesion showed a significant reduction of width along the
      length of a single B-scan, at Month 12 follow-up visit (P < 0.001). It is notable
      that a small "discreet" pigment epithelial detachment associated with the highly
      reflective subretinal lesions was present in 28 of 29 eyes at baseline and after
      treatment (at Month 12 follow-up visit). CONCLUSION: A discreet pigment
      epithelial detachment represents a common associated finding of classic choroidal
      neovascularization. Our study demonstrated that anti-vascular endothelial growth
      factor treatment may not only stop the growth of the highly reflective subretinal
      lesion that colocalize with the classic choroidal neovascularization but also
      determine its regression.

PMID- 22466477
TI  - Inhibitory activity of ranibizumab, sorafenib, and pazopanib on light-induced
      overexpression of platelet-derived growth factor and vascular endothelial growth
      factor A and the vascular endothelial growth factor A receptors 1 and 2 and
      neuropilin 1 and 2.
AB  - BACKGROUND: Cumulative light exposure is significantly associated with
      progression of age-related macular degeneration. Growth factors and growth factor
      receptor signaling are known to have a substantial impact on the development of
      age-related macular degeneration. This study explored the effects of ranibizumab,
      sorafenib, and pazopanib on vascular endothelial growth factor A (VEGF) receptors
      1 and 2 and neuropilin 1 and 2 expression in human retinal pigment epithelial
      cells. In addition, their effects on light-induced overexpression of VEGF and
      platelet-derived growth factor were investigated. METHODS: Primary human retinal
      pigment epithelial cells were exposed to white light and then treated with
      ranibizumab (0.125 mg/mL), sorafenib (1 MUg/mL), or pazopanib (1 MUg/mL).
      Viability of cells, expression of VEGF receptors 1 and 2 and neuropilin 1 and 2
      and their mRNA, and secretion of VEGF and platelet-derived growth factor were
      investigated by reverse transcription-polymerase chain reactions,
      immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: Treatment
      with sorafenib or pazopanib reduced the expression of VEGF receptors 1 and 2 and
      neuropilin 1, and sorafenib also reduced neuropilin 2. Light exposure decreased
      cell viability and increased expression and secretion of VEGF and platelet
      derived growth factor. Sorafenib and pazopanib significantly reduced light
      induced overexpression and secretion of VEGF and platelet-derived growth factor.
      Ranibizumab reduced secreted VEGF in cell culture supernatants only. CONCLUSION:
      Our in vitro results suggest that multikinase inhibitors have promising
      properties as a potential antiangiogenic treatment for age-related macular
      degeneration.

PMID- 22466478
TI  - Treatment of retinal detachment secondary to macular hole in high myopia:
      vitrectomy with dissection of the inner limiting membrane to the edge of the
      staphyloma and long-term tamponade.
AB  - PURPOSE: To evaluate the rates of retinal reattachment and the closure of myopic
      macular hole because of posterior pole retinal detachment after treatment with
      pars plana vitrectomy and subsequent dissection of the inner limiting membrane.
      METHODS: Prospective noncomparative study of 27 eyes from 27 phakic patients
      diagnosed with posterior pole retinal detachment as a result of myopic macular
      hole. All underwent pars plana vitrectomy with dissection of the inner limiting
      membrane and intravitreal silicone oil tamponade performed by the same surgeon.
      The main variables assessed were visual acuity, retinal reattachment, and macular
      hole closure determined by optical coherence tomography. RESULTS: Of the 27 eyes,
      16 (59.3%) were right eyes and 11 (40.7%) were left eyes. Mean age was 50.5
      years. Myopia ranged from -9 diopters (D) to -27 diopters (mean, -18 diopters),
      and axial length ranged from 28.5 mm to 35.6 mm (mean, 32.05 mm). After a mean
      postoperative period of 12 months, retinal reattachment was found in 85.1% of the
      patients and anatomical closure of the macular hole in 51.9%. CONCLUSION: This
      technique offers good rates of retinal reattachment and macular hole closure,
      although seldom increases the final visual acuity. It showed limited
      effectiveness in eyes with an axial length >30 mm.

PMID- 22466479
TI  - Morphologic and functional evaluation before and after successful macular hole
      surgery using spectral-domain optical coherence tomography combined with
      microperimetry.
AB  - PURPOSE: To evaluate photoreceptor inner/outer segment (IS/OS) defects, best
      corrected visual acuity (BCVA), macular sensitivity, and fixation stability to
      correlate morphologic changes with visual functional outcomes at different stages
      after macular hole surgery using spectral-domain optical coherence tomography
      combined with microperimetry. METHODS: This study was an interventional,
      retrospective case series. Sixteen eyes of 16 patients with successfully operated
      idiopathic full-thickness macular holes were included in this study. The IS/OS
      defect maximal diameter and area, BCVA, central macular sensitivity, mean macular
      sensitivity, and fixation stability were measured using spectral-domain optical
      coherence tomography combined with microperimetry, preoperatively, and with a
      follow-up of 3 months postoperatively. RESULTS: Both the IS/OS defect diameter
      and area improved after successful macular hole surgery (P < 0.001; P < 0.001).
      The BCVA, central macular sensitivity, mean macular sensitivity, and fixation
      stability of the central 2 degrees  also improved (P = 0.001; P = 0.004; P =
      0.036; P = 0.031). Stable BCVA improvement was achieved as early as 1-month
      postoperation despite continuous repair of the IS/OS junction defect diameter and
      area and improvement in fixation and macular sensitivity within the first 3
      months after surgery. The postoperative central macular sensitivity and mean
      macular sensitivity negatively correlated with preoperative linear IS/OS junction
      defect diameter (P = 0.033; P = 0.006) and the defect area (P < 0.001; P =
      0.002). However, the postoperative BCVA and the improvement in BCVA, macular
      sensitivity, and fixation stability were not correlated with preoperative IS/OS
      defect diameter or area. CONCLUSION: Continuous anatomical and functional
      improvements can be observed after successful microinvasive macular hole surgery.
      The preoperative extent of the IS/OS junction defect is of good predictive value
      for postoperative macular sensitivity. However, the factors that influence BCVA
      are multiple. Prediction of BCVA based on a single anatomical parameter or
      assessment of macular function only based on BCVA should be avoided.

PMID- 22466480
TI  - Effect of combination therapy with bevacizumab and dexamethasone intravitreal
      implant in patients with retinal vein occlusion.
AB  - OBJECTIVE: The objective of this study was to determine if dexamethasone
      intravitreal implant 0.7 mg (Ozurdex; Allergan, Inc) with bevacizumab (Avastin;
      Genentech, Inc) therapy can be synergistic, providing further improvements in
      visual acuity, sustainability, and macular thickness when compared with
      dexamethasone intravitreal implant 0.7 mg alone. METHODS: This is a prospective,
      interventional case series intended to monitor changes in visual acuity and
      macular thickness in patients diagnosed with retinal vein occlusion (RVO), after
      injection of bevacizumab followed by a scheduled dexamethasone intravitreal
      implant. This study was designed to emulate patient care as received in the
      typical ophthalmology practice. Patients diagnosed with RVO, who were seen
      between September 2009 and July 2010, were included in this study if they had
      received previous anti-vascular endothelial growth factor therapy. Patients were
      included in analysis if the previous anti-vascular endothelial growth factor
      therapy was at least 6 weeks before and optical coherence tomography (OCT) was
      >300 MUm on spectral-domain OCT. Exclusion criteria included history of
      vitrectomy, and/or rubeotic or advanced glaucoma. All patients were evaluated
      with Snellen visual acuity and measured for macular thickness (calculated by
      spectral-domain OCT) and intraocular pressure. At baseline, all patients were
      injected with bevacizumab, followed by dexamethasone intravitreal implant
      injection 2 weeks later. These patients were reexamined on a monthly basis and
      retreated when edema occurred. RESULTS: The primary outcome measure was the time
      to reinjection based on OCT and vision criteria. The secondary outcomes were
      increases in visual acuity and the reduction of OCT thickness during that period.
      Thirty-four eyes of 33 patients, with a mean age of 72.8 years, were identified.
      Thirty-five percent were diagnosed with central RVO, while the other 65% were
      with branch RVO. Of these patients, 97% gained vision during the study. Mean
      visual acuity improved from initially 11 letters to a maximum of 25 letters
      during the study period. In addition, vision improved by at least 15 letters in
      29% of patients initially up to 64% during the study period. Macular thickness
      decreased with the combination treatment by OCT, and the effect continued an
      average of 126 days from the initial bevacizumab treatment. Retreatment was
      unnecessary in 18% of the population during the 6-month study period. CONCLUSION:
      This study demonstrates efficacy and the duration of effect using a combination
      of bevacizumab and dexamethasone versus dexamethasone alone. The combination is
      synergistic, increasing visual acuity and prolonging the time between injections,
      compared with either of these medications alone. Therefore, the combination of a
      vascular endothelial growth factor inhibitor and a dexamethasone implant may be a
      valuable option for RVO treatment.

PMID- 22466482
TI  - Half-fluence photodynamic therapy in acute central serous chorioretinopathy.
AB  - PURPOSE: To evaluate the results of indocyanine green angiography-guided
      verteporfin (Visudyne; Novartis Pharma AG, Switzerland) photodynamic therapy with
      half-fluence rate in the treatment of acute symptomatic central serous
      chorioretinopathy. METHODS: A retrospective review over 12 months was performed
      of 19 consecutive patients with subfoveal fluid because of acute symptomatic
      central serous chorioretinopathy proved by spectral-domain optical coherence
      tomography and fluorescein angiography, treated with indocyanine green
      angiography-guided verteporfin (6 mg/m) photodynamic therapy with half-fluence
      rate (25 J/cm). Acute symptomatic central serous chorioretinopathy was defined as
      first episode of symptoms and duration of symptoms before treatment of <=12
      weeks. RESULTS: Best-corrected visual acuity at baseline was 47 letters (+/-10; n
      = 19) according to the Early Treatment Diabetic Retinopathy Study chart. At 12
      months after photodynamic therapy, the mean best-corrected visual acuity improved
      to 56 letters (P = 0.003).Pretreatment central foveal thickness was 406 MUm and
      decreased by a mean of 163 MUm at Month 12 control (P < 0.001). At Month 1 after
      photodynamic therapy, subretinal fluid in spectral-domain optical coherence
      tomography was completely resolved in all 19 patients. None of the patients
      developed any recurrence of symptoms over 12 months. No ocular or systemic side
      effects were observed during 12 months follow-up. CONCLUSION: Indocyanine green
      angiography-guided half-fluence photodynamic therapy with verteporfin is
      effective in treating acute symptomatic central serous chorioretinopathy,
      resulting in visual improvement and complete resolution of exudative macular
      detachment.

PMID- 22466483
TI  - Evaluation of peripapillary intrachoroidal cavitation with swept source and
      enhanced depth imaging optical coherence tomography.
AB  - PURPOSE: To investigate the anatomic characteristics of peripapillary
      intrachoroidal cavitation using optical coherence tomography methodologies that
      are capable of deeper tissue penetration and consider pathophysiologic mechanisms
      of disease on the basis of the derived imaging information. METHODS: Consecutive
      eyes with peripapillary intrachoroidal cavitation were imaged with swept source
      optical coherence tomography with a 1-mm light source and in one eye with
      enhanced depth imaging spectral domain optical coherence tomography and 3
      dimensional rendering. The anatomic layers were identified, and the induced
      abnormalities were evaluated. RESULTS: There were 16 eyes of 13 patients who had
      a mean age of 50.3 years and a mean spherical refraction of -12.5 diopters in the
      affected eyes. The lesion appeared as a yellowish-orange lobular region, usually
      inferior to the optic nerve, which was invariably tilted. The sclera was bowed
      posteriorly under the region of the intrachoroidal cavitation, while the
      overlying retina-retinal pigment epithelium-Bruch membrane complex showed little,
      if any deformation. Full-thickness defects in the retina at the inferior border
      of the conus were seen in four eyes and were associated with prominent cavitation
      within the choroid with marked posterior bowing of the sclera, but negligible
      deformation of the overlying retina inferior to the nerve. CONCLUSION: Newer
      imaging modalities provided information about deeper structures in the eye not
      available in older studies that were performed with time-domain optical coherence
      tomography. This study demonstrated posterior deformation of the sclera in
      regions previously thinned by the ocular expansion that occurs in high myopia and
      imaged the resultant effects on the involved choroid.

PMID- 22466485
TI  - Spectral-domain optical coherence tomography imaging of retinal changes after
      conventional multicolor laser, subthreshold micropulse diode laser, or pattern
      scanning laser therapy in Japanese with macular edema.
AB  - PURPOSE: To perform optical coherence tomography imaging of retinal healing after
      conventional multicolor laser, pattern scanning laser, or micropulse laser
      treatment and compare the characteristics of each method. METHODS: This was a
      single-center interventional case series study. Twenty-nine patients with macular
      edema underwent laser photocoagulation. Changes of retinal morphology because of
      laser-tissue interaction were assessed within 3 months by using a spectral-domain
      optical coherence tomography. RESULTS: Immediately after conventional multicolor
      laser or pattern scanning laser treatment, a hyperreflective band appeared at the
      laser sites. The photoreceptor inner segment-outer segment line disappeared in
      all the patients treated with a conventional multicolor laser, but was intact in
      22.2% (2/9 eyes) after pattern scanning laser. From 1 week to 1 month, the bands
      resolved. At 3 months, recovery of the inner segment-outer segment line
      surrounding the laser site was seen in all patients after conventional grid
      photocoagulation and pattern scanning laser. Retinal morphology did not change at
      any time during the observation period after subthreshold micropulse diode laser
      photocoagulation. CONCLUSION: The characteristic in vivo effects of retinal
      photocoagulation were monitored over time by spectral-domain optical coherence
      tomography. Changes of retinal morphology appeared less intense after pattern
      scanning laser than conventional grid laser treatment.

PMID- 22466484
TI  - Sector laser photocoagulation for the prevention of macular edema after plaque
      radiotherapy for uveal melanoma: a pilot study.
AB  - OBJECTIVE: To investigate the role of sector laser photocoagulation for
      prevention of macular edema after plaque radiotherapy for uveal melanoma.
      METHODS: Noncomparative, pilot interventional case series. The main outcome
      measure was optical coherence tomography-evident macular edema. RESULTS: A total
      of 29 patients had sector laser photocoagulation (sector panretinal
      photocoagulation) and sub-Tenon triamcinolone injection. The median tumor
      thickness and base was 3.3 mm and 10.0 mm. The median radiation dose and rate to
      the macula was 2,944 cGy and 31.0 cGy/hour. At the 12-month and 24-months follow
      up, cystoid macular edema was found in 17% and 24% of the sector panretinal
      photocoagulation group. There were no major side effects registered. CONCLUSION:
      Sector panretinal photocoagulation in combination with sub-Tenon triamcinolone
      appears to show potential as a safe and beneficial intervention for the
      prevention of macular edema after plaque radiotherapy for uveal melanoma in this
      series.

PMID- 22466486
TI  - Hybrid 20/23-gauge pars plana vitrectomy for retained lens fragments after
      cataract surgery.
AB  - PURPOSE: To evaluate the outcome and surgery-associated risks in patients
      undergoing 23-gauge pars plana vitrectomy (PPV) for retained lens fragments.
      METHODS: Retrospective analysis of 42 eyes of 42 consecutive patients at a
      tertiary teaching hospital in Sydney (Australia) during a period of 4 years.
      Evaluation of final visual acuity, complications, differences in patients
      receiving an intraocular lens at the primary cataract surgery, and differences in
      final visual acuity regarding the usage of a phacofragmatome and analysis of pars
      plana vitrectomy-related complications. RESULTS: The majority (83.3%) achieved a
      visual acuity of 0.3 (logarithm of the minimum angle of resolution) or better,
      and 19 eyes (45.2%) achieved a final visual acuity of 0 (logarithm of the minimum
      angle of resolution). Overall, 95.2% of the eyes had a better postoperative
      visual acuity compared with the preoperative visual acuity. There were no
      differences in proportions regarding the final visual acuity in patients who had
      an intraocular lens at the time of the pars plana vitrectomy and those who had a
      secondary lens implant. A retinal detachment after the lens fragment removal was
      observed in 2 eyes. CONCLUSION: Dropped lens fragments because of complicated
      cataract surgery can be managed well with 23-gauge pars plana vitrectomy: The
      majority of patients achieve a good visual acuity despite 2 surgeries at a rather
      low rate of retinal complications.

PMID- 22466487
TI  - Time course of changes in aqueous flare intensity after vitrectomy for
      rhegmatogenous retinal detachment.
AB  - PURPOSE: To investigate the time course of changes in aqueous flare intensity
      after vitrectomy for rhegmatogenous retinal detachment (RD) and to determine the
      clinical factors related to an increase in aqueous flare. METHODS: The present
      study included 22 unilateral patients with RD undergoing primary 20-gauge
      vitrectomy. Aqueous flare intensity was measured preoperatively and at 1 week, 2
      weeks, 1 month, and 3, 6, and 12 months postoperatively using the laser flare
      meter. RESULTS: Before vitrectomy, aqueous flare intensity was significantly
      higher in eyes with RD than in contralateral normal eyes. Vitrectomy increased
      aqueous flare intensity, and the peak was observed at the first postoperative
      week. Aqueous flare intensity decreased to a stable level at 3 months
      postoperatively but remained significantly higher than that of contralateral and
      preoperative eyes throughout the observation period. Clinical factors that were
      found to be significantly correlated with an increase in aqueous flare intensity
      included 1) before the surgical procedure: extent of RD and intraocular pressure,
      and 2) 3 months postoperatively: size of retinal breaks, number of laser
      photocoagulation spots, operation time, and performance of combined cataract
      surgery. Multiple regression analysis revealed that aqueous flare intensity at 3
      months postoperatively had significant correlation with the size of retinal
      breaks (P < 0.005) and the number of laser photocoagulation spots (P < 0.05).
      CONCLUSION: Aqueous flare intensity after vitrectomy for RD decreased to a stable
      level at 3 months postoperatively but remained significantly higher than the
      normal level. The size of retinal breaks and the degree of surgical invasion were
      associated with the increase in aqueous flare.

PMID- 22466488
TI  - Tissue attraction associated with 20-gauge, 23-gauge, and enhanced 25-gauge dual
      pneumatic vitrectomy probes.
AB  - PURPOSE: To evaluate the influence of different vitrectomy probe gauge sizes and
      their fluidics, under various vacuum settings, on tissue attraction. METHODS: An
      apparatus was designed to model the retinal membrane during vitrectomy. A
      cantilever beam was constructed from a wire (diameter, 0.076 mm) with a latex
      strip (simulating ocular membranes) attached at a right angle to its tip. The
      beam was clamped vertically in a container of balanced salt solution. The port of
      the vitrectomy probe (20 gauge, 23 gauge, and enhanced 25 gauge) was aligned with
      the membrane. With the cutter off, the vacuum was increased until the membrane
      was attracted into the port. The aspiration flow rate was measured with a
      noninvasive flow meter. Attraction distance, vacuum pressure, and flow rate were
      recorded. RESULTS: For any given distance, the 20-gauge probe needed the lowest
      amount of vacuum and the highest aspiration flow, while the enhanced 25-gauge and
      23-gauge probes needed larger vacuum and smaller aspiration flow rates to attract
      the membrane into the port. CONCLUSION: The sphere of influence on surrounding
      tissue was greatest with large-gauge vitrectomy probes. This laboratory model
      indicated that small-gauge probes could be used to target specific tissues while
      minimizing the effects on adjacent tissue structures.

PMID- 22466489
TI  - Fundus autofluorescence not predictive of treatment response to intravitreal
      bevacizumab in exudative age-related macular degeneration.
AB  - PURPOSE: Foveal autofluorescence (AF) has been suggested to be a potential
      predictor of treatment outcome in choroidal neovascularization (CNV) secondary to
      age-related macular degeneration and could be a useful marker to help
      prognosticate for patients and for clinical trials. This retrospective study aims
      to determine if pretreatment foveal AF can predict treatment response to
      intravitreal bevacizumab monotherapy in CNV secondary to age-related macular
      degeneration. METHODS: Ninety-five eyes (85 patients) with naive CNV secondary to
      age-related macular degeneration, treated with intravitreal bevacizumab
      monotherapy were included in this study. Lesion size, CNV type on fluorescein
      angiography, pretreatment best-corrected visual acuity, and foveal AF pattern
      (intact/nonintact) were used as predictors. Multivariate linear regression and
      logistic regression were performed using best-corrected visual acuity change and
      anatomical response at 6 months as the dependent variables separately. RESULTS:
      Pretreatment foveal AF (intact or nonintact) did not predict visual outcome (P =
      0.17) nor did lesion size (P = 0.2) or CNV type (P = 0.61). Foveal AF did
      correlate with the visual acuity but it did not predict any treatment response.
      Pretreatment best-corrected visual acuity was the only predictive factor for the
      visual outcome (P = 0.043). CONCLUSION: Pretreatment AF is not a predictor for
      the treatment response to intravitreal bevacizumab monotherapy in eyes with CNV
      secondary to age-related macular degeneration.

PMID- 22466490
TI  - Subretinal drusenoid deposits associated with pigment epithelium detachment in
      age-related macular degeneration.
AB  - PURPOSE: To characterize retrospectively subretinal drusenoid deposits (SDD) in
      patients with pigment epithelium detachment (PED) secondary to age-related
      macular degeneration. METHODS: Confocal scanning laser ophthalmoscopy near
      infrared reflectance images (820 nm) were recorded in 208 eyes of 104 patients
      with serous, drusenoid, or vascularized PED because of age-related macular
      degeneration in at least 1 eye. The digital images were evaluated by two
      independent readers with subsequent senior reader arbitration for prevalence of
      SDD. RESULTS: Serous PED was present in only two patients and was therefore not
      included in the statistical analysis. Subretinal drusenoid deposits were detected
      in 55 of 102 (53.9%) patients in at least 1 eye. Forty-six of those 55 patients
      showed SDD bilaterally (83.6%). Subretinal drusenoid deposits were present in 51
      (50%) right eyes and 50 (49.0%) left eyes. One hundred and forty-six of 204 eyes
      showed a PED secondary to age-related macular degeneration of which 111 (76%)
      were vascularized and 35 (24%) drusenoid. Prevalence of SDD was correlated with
      age (P < 0.0001) and female gender (P = 0.014), but not with the type of PED (P =
      0.174). Cohen kappa statistics showed good interobserver agreement for infrared
      imaging (0.78 for right eyes, 0.74 for left eyes). CONCLUSION: Subretinal
      drusenoid deposits represent a common phenotypic characteristic in eyes with PED
      because of age-related macular degeneration . As described in previous studies,
      SDD are readily identified using confocal scanning laser ophthalmoscopy imaging
      technology. Future studies should pursue the pathophysiologic role and the
      predictive value of the presence of SDD in the development of PED and a
      subsequent rip of the retinal pigment epithelium.

PMID- 22466491
TI  - Clinical spectrum and prognosis of uveal melanoma based on age at presentation in
      8,033 cases.
AB  - PURPOSE: To evaluate clinical features and life prognosis of uveal melanoma based
      on age at presentation. DESIGN: Retrospective, nonrandomized, interventional case
      series. RESULTS: Of 8,033 eyes with uveal melanoma, 106 (1%) were in young
      patients (<=20 years), 4,287 (53%) in mid adults (21-60 years), and 3,640 (45%)
      in older adults (>60 years). Based on age (young, mid adults, and older adults)
      at presentation, tumor epicenter was located in iris (21, 4, 2%; P < 0.0001),
      ciliary body (8, 5, and 7%; P = 0.0225), or choroid (71, 91, and 90%; P <
      0.0001). Mean tumor diameter (10.2, 10.8, 11.5 mm; P < 0.0001), mean tumor
      thickness (5.0, 5.3, 5.7 mm; P < 0.0001), and extraocular extension (1, 2, and
      4%; P = 0.0004) increased with age. Kaplan-Meier estimates of tumor-related
      metastasis at 3, 5, 10, and 20 years were 2%, 9%, 9%, and 20% in young patients
      (P < 0.011); 6%, 12%, 23%, and 34% in mid adults (P < 0.0001); and 11%, 19%, 28%,
      and 39% in older adults. Kaplan-Meier estimate of tumor-related death at 3, 5,
      10, and 20 years were 0%, 2%, 5%, and 17% in young patients (P = 0.08); 3%, 6%,
      11%, and 17% in mid adults (P < 0.001); and 7%, 11%, 16%, and 20% in older
      adults. CONCLUSION: Compared with mid adults and older adults, young patients
      manifested a higher proportion of iris melanoma. Compared with older adults,
      young and mid adults showed smaller melanoma basal dimension and lower tumor
      related metastasis and death.

PMID- 22466492
TI  - Intracameral illuminator-guided advanced lens capsule polishing during cataract
      surgery in eyes with diabetic retinopathy.

PMID- 22466493
TI  - Prevalence and risk factors for severity of diabetic neuropathy in type 2
      diabetes mellitus.
AB  - PURPOSE: To estimate the prevalence of diabetic neuropathy (severity wise) and
      associated risk factors in a population having type 2 diabetes mellitus.
      MATERIALS AND METHODS: A population-based sample of 1401 persons with diabetes
      (identified as per the WHO criteria) underwent comprehensive eye examination
      including stereoscopic digital photography (45 degrees  four field) for diabetic
      retinopathy grading. Vibration perception threshold (VPT) measurements were done
      to assess neuropathy (cut off >= 20 V). Severity of neuropathy was graded into
      three groups based on VPT score as mild (20-24.99 V), moderate (25-38.99 V), and
      severe (>=39 V). Univariate and multivariate analyses were done to find out the
      independent risk factors for severity of diabetic neuropathy. RESULTS: In the
      overall group, the prevalence of diabetic neuropathy was 18.84% (95% CI: 16.79
      20.88). The prevalence of mild diabetic neuropathy was 5.9% (95% CI: 4.68-7.15),
      moderate diabetic neuropathy was 7.9% (95% CI: 6.50-9.33), and severe diabetic
      neuropathy was 5% (95% CI: 3.86-6.14). Increasing age per year (P < 0.0001) was a
      statistically significant risk factor for all - mild, moderate, and severe -
      types of diabetic neuropathy. For severe diabetic neuropathy, other significant
      risk factors were duration of diabetes mellitus (P = 0.027), macroalbuminuria (P
      = 0.001), and presence of diabetic retinopathy (P = 0.020). CONCLUSIONS: The
      results suggested that every fifth individual in a population of type 2 diabetes
      is likely to have diabetic neuropathy. Nearly 13% had neuropathy of moderate and
      severe category, making this group vulnerable for complications such as foot
      ulceration or lower limb amputation.

PMID- 22466494
TI  - Acute perforated appendicitis: an analysis of risk factors to guide surgical
      decision making.
AB  - INTRODUCTION: Acute perforated appendicitis is associated with increased post
      operative morbidity and mortality. Avoiding delays in surgery in these patients
      may play a role in reducing observed morbidity. OBJECTIVE: To analyze the clinico
      pathological profile and outcomes in a cohort of patients undergoing emergency
      appendicectomies for suspected acute appendicitis and to determine factors
      influencing the risk of perforated appendicitis in order to aid better
      identification of such patients and develop protocols for improved management of
      this subset of patients. MATERIALS AND METHODS: A retrospective analysis of
      patients undergoing emergency appendicectomies following presentation with acute
      appendicitis to the Modbury hospital, South Australia from March 2007 to April
      2011 was conducted. Statistical analyses were performed in SAS 9.2. RESULTS AND
      DISCUSSION: 506 patients underwent emergency appendectomy for acute appendicitis
      which included equal number of male and female patients with a median age of 25
      years. Perforated appendicitis was found in 102 (20%) patients. Post-operative
      morbidity was significantly higher in patients with perforated appendicitis
      (28.4% vs 4.7%; P<0.0001). Male sex, patients older than 60 years, along with
      raised neutrophil counts and C-reactive protein levels were found to be
      significantly associated with the risk of perforation (P<0.05). CONCLUSIONS:
      Acute perforated appendicitis is associated with high morbidity. The increased
      risk of perforation in males and elderly patients appears unrelated to delays in
      presentation, diagnosis, or surgery. Patients with clinically diagnosed acute
      appendicitis and an elevation in neutrophil count and CRP level must be
      considered candidates for early surgery as they are likely to have an
      appendicular perforation.

PMID- 22466495
TI  - Voice in chronic hemodialyzed individuals.
AB  - OBJECTIVE: Chronic hemodialysis affects various body systems, one of which is the
      respiratory system. Since respiration is the prime source for speech, vocal
      dysfunctions are expected to be present in patients with chronic hemodialysis.
      The present study attempts to shed light on the changes in acoustic and
      aerodynamic characteristics of voice, if any, in patients with chronic
      hemodialysis. MATERIALS AND METHODS: Phonation of sustained vowel/a/sample was
      subjected to acoustic analysis using VAGHMI software. Sustained duration
      of/a/,/s/, and/z/ was recorded for the purpose of aerodynamic analysis. The
      independent t test was employed to find the significant difference between the
      two groups. RESULTS: Chronic hemodialyzed subjects showed significant deviation
      in frequency, perturbation, and aerodynamic measures when compared to normal
      subjects. These results are discussed with respect to the underlying
      pathophysiology. CONCLUSION: The results of the present study revealed that
      subjects with chronic hemodialysis exhibit clinical evidence of voice disorders.
      Vocal deviations in chronic hemodialyzed subjects are explained due to the
      influence of the renal system on the respiratory and the phonatory system and the
      negative fluid balance effect of hemodialysis.

PMID- 22466496
TI  - Validation of the children's depression rating scale- revised for adolescents in
      primary-care pediatric use in India.
AB  - BACKGROUND: Adolescent depression needs to be identified and treated in the
      primary care settings. There is no clinician-rated measure validated in India for
      identifying depression among adolescents. AIM: We studied the diagnostic
      accuracy, reliability, and validity of Children's Depression Rating Scale -
      Revised (CDRS-R) for primary care pediatrics. SETTING AND DESIGN: Prospective
      study in three schools in Southern India. MATERIALS AND METHODS: Adolescents
      recruited were administered the CDRS-R by a pediatrician and clinical
      psychologist along with Beck Depression Inventory (BDI) for convergent validity.
      Impact of Event Scale (IES) for divergent validity and the ICD-10 clinical
      diagnosis of depressive disorders using modified Kiddie-SADS-Present and Lifetime
      Version (K-SADS-PL) interview as reference standard were administered by a
      psychiatrist independently. Appropriate statistical analyses for diagnostic
      accuracy, reliability, and validity were done. RESULTS: A cut-off score of 30
      (sensitivity = 83%, specificity = 84%; AUC in ROC = 87%) in CDRS-R is suggested
      for diagnosing depression. The inter-rater reliability (r = 0.73) and test-retest
      reliability (r = 0.98) was good. In addition to the adequate face and content
      validity, CDRS-R had good internal consistency (alpha = 0.76), high convergent (r
      = 0.71; P = 0.001), and divergent validity (r = 0.28; P = 0.20). There was
      moderate concordance with the reference standard of ICD-10 diagnosis (45.5%) in
      identifying depression and CDRS-R discriminated 80% of the other psychiatric
      morbidity. The six-factor structure explained 60.6% of variance. CONCLUSION: The
      CDRS-R showed strong psychometric properties and is now available for use in the
      primary-care pediatric practice in India.

PMID- 22466497
TI  - A case of losartan induced angioedema.
AB  - Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers
      (ARB) target the renin-angiotensin system and are used in the management of
      hypertension. Both classes of drugs have similar side effects. ARBs are
      considered to be much better tolerated than ACE inhibitors with lesser incidence
      of side effects. Angioedema is a very rare side effect associated with ACE
      inhibitors (ACEI) and even rarer so with ARBs. The cause for angioedema in ACE
      inhibitors is said to be the rise in bradykinin levels. It has been postulated
      that angiotensin II receptor activates the bradykinin-prostaglandin-nitric oxide
      cascade, resulting in bradykinin-mediated side effects of ARBs such as
      angioedema, but the true mechanism remains largely unknown. We present here a
      rare case of late onset angioedema associated with losartan (an ARB) in a female
      patient. She had been started on an ARB as a first line treatment for
      uncomplicated mild to moderate hypertension. She had no prior exposure to ACE
      inhibitors and did not have any other significant medical history. Though rare
      angioedema is a serious recognized side effect of ARB therapy and the patients
      started on them should be warned to look for the early signs so as to take
      corrective action.

PMID- 22466498
TI  - Subarachnoid hemorrhage with transient ischemic attack: another masquerader in
      cerebral venous thrombosis.
AB  - Cerebral venous thrombosis has a wide spectrum of clinical manifestations that
      may mimic many other neurological disorders and lead to frequent misdiagnoses or
      delay in diagnosis. The most frequent symptoms and signs are headache, seizures,
      focal deficits, and papilledema. A number of rare atypical manifestations have
      been described. Cerebral venous thrombosis may present with an isolated
      intracranial hypertension type picture, thunderclap headache, attacks of migraine
      with aura, isolated psychiatric disturbances, pulsatile tinnitus, isolated or
      multiple cranial nerve involvement, and occasionally as subarachnoid hemorrhage
      (SAH) or transient ischemic attack. Our patient presented with thunderclap
      headache and transient ischemic attack like episode with obvious SAH on CT scan.
      Acute SAH suggests the presence of a vascular lesion, such as ruptured aneurysm,
      and CVT is not generally considered in the diagnostic workup of SAH. The case
      emphasizes the importance of cerebral venous study in nonaneurysmal cases of SAH.
      It is important to have a high index of suspicion in such atypical cases to avoid
      delay in diagnosis.

PMID- 22466499
TI  - Steroid responsive prolonged thrombocytopenia in dengue.
AB  - Prolonged thrombocytopenia in a usual case of dengue virus infection is uncommon.
      Dengue-related thrombocytopenia is self-limiting and responds within 3-5 days. An
      underlying immunological disorder may be responsible for delayed return of
      platelet count to a normal level. We present a case of prolonged thrombocytopenia
      in a case of dengue hemorrhagic fever. The response to steroids suggests a
      possible immunological dysfunction.

PMID- 22466500
TI  - Melioidotic pericardial effusion.
AB  - Aim is to present a rare case of purulent pericardial effusion caused by
      Burkholderia pseudomallei. Pericardial sample was inoculated into Bactec Peds
      Plus/F broth of the Bactec automated system. After the system flagged positive,
      the broth was subjected to Gram stain, biochemical tests and drug susceptibility.
      The organism was identified as Burkholderia pseudomallei. Tuberculosis (TB) is
      the most common cause of pericarditis in countries where it remains a major
      public health problem, but in the western coastal districts of India, clinicians
      and microbiologists alike must be aware of Burkholderia pseudomallei a rare cause
      of pericarditis that can be misdiagnosed as TB pericarditis.

PMID- 22466501
TI  - Electrophysiological correlates of impaired reading in dyslexic pre-adolescent
      children.
AB  - In this study, event related potentials (ERPs) were used to investigate the
      extent to which dyslexics (aged 9-13 years) differ from normally reading controls
      in early ERPs, which reflect prelexical orthographic processing, and in late
      ERPs, which reflect implicit phonological processing. The participants performed
      an implicit reading task, which was manipulated in terms of letter-specific
      processing, orthographic familiarity, and phonological structure. Comparing
      consonant- and symbol sequences, the results showed significant differences in
      the P1 and N1 waveforms in the control but not in the dyslexic group. The reduced
      P1 and N1 effects in pre-adolescent children with dyslexia suggest a lack of
      visual specialization for letter-processing. The P1 and N1 components were not
      sensitive to the familiar vs. less familiar orthographic sequence contrast. The
      amplitude of the later N320 component was larger for phonologically legal
      (pseudowords) compared to illegal (consonant sequences) items in both controls
      and dyslexics. However, the topographic differences showed that the controls were
      more left-lateralized than the dyslexics. We suggest that the development of the
      mechanisms that support literacy skills in dyslexics is both delayed and follows
      a non-normal developmental path. This contributes to the hemispheric differences
      observed and might reflect a compensatory mechanism in dyslexics.

PMID- 22466502
TI  - Do equilibrium constraints modulate postural reaction when viewing imbalance?
AB  - Action observation and action execution are tightly coupled on a
      neurophysiological and a behavioral level, such that visually perceiving an
      action can contaminate simultaneous and subsequent action execution. More
      specifically, observing a model in postural disequilibrium was shown to induce an
      increase in observers' body sway. Here we reciprocally questioned the role of
      observers' motor system in the contagion process by comparing participants' body
      sway when watching displays of antero-posterior vs. lateral imbalance. Indeed,
      during upright standing, biomechanical constraints differ along the antero
      posterior (A-P) and medio-lateral (M-L) axes; hence an impact of observers'
      postural constraints on the contagion response would result in different
      reactions to both types of stimuli. In response to the displays, we recorded
      greater area of center of pressure (CoP) displacement when watching
      forward/backward compared to left/right imbalance. In addition, after normalizing
      A-P and M-L CoP displacements by a control condition (fixation cross), A-P CoP
      path length when viewing forward imbalance tended to be higher than M-L CoP path
      length when viewing imbalance to the left or right. These results indicate that
      postural contagion is promoted when the display is compatible with observers'
      motor stabilization strategy which is mainly oriented along the A-P axis. In
      terms of clinical application, this study brings new indications for adaptation
      of observational training devices in rehabilitation programs.

PMID- 22466503
TI  - Effect of motion on the ADC quantification accuracy of whole-body DWIBS.
AB  - BACKGROUND AND METHODS: Diffusion-weighted whole-body imaging with background
      body signal subtraction was introduced as a qualitative approach to detecting
      metastases in the body. A liver-mimicking phantom with embedded tumours that
      could be moved to replicate respiratory motion was developed to assess its
      ability to accurately quantify ADC values. RESULTS: Mean tumour ADC values were
      unaltered by the motion; however, a significant (p < 0.05) increase in the spread
      of ADC values was measured, even for relatively large tumours. CONCLUSIONS: These
      findings may be of significance in cancer therapy monitoring where subtle changes
      in ADC histograms may reveal changes in tumour heterogeneity.

PMID- 22466505
TI  - Oscillatory dynamics in the hippocampus support dentate gyrus-CA3  coupling.
AB  - Gamma oscillations in the dentate gyrus and hippocampal CA3 show variable
      coherence in vivo, but the mechanisms and relevance for information flow are
      unknown. We found that carbachol-induced oscillations in rat CA3 have biphasic
      phase-response curves, consistent with the ability to couple with oscillations in
      afferent projections. Differences in response to stimulation of either the
      intrinsic feedback circuit or the dentate gyrus were well described by varying an
      impulse vector in a two-dimensional dynamical system, representing the relative
      input to excitatory and inhibitory neurons. Responses to sinusoidally modulated
      optogenetic stimulation confirmed that the CA3 network oscillation can entrain to
      periodic inputs, with a steep dependence of entrainment phase on input frequency.
      CA3 oscillations are therefore suited to coupling with oscillations in the
      dentate gyrus over a broad range of frequencies.

PMID- 22466507
TI  - Enhancing the Stokes' shift of BODIPY dyes via through-bond energy transfer and
      its application for Fe(3+)-detection in live cell imaging.
AB  - Two energy transfer cassettes that exhibit a large pseudo Stokes' shift (up to
      400 nm) due to efficient through-bond energy transfer (up to 99%) have been
      constructed. Selective binding of Fe(III) with the donor entity significantly
      suppresses the excitation energy transfer resulting in fluorescence quenching in
      aqueous solution and in living cells.

PMID- 22466506
TI  - An evolutionary recent neuroepithelial cell adhesion function of  huntingtin
      implicates ADAM10-Ncadherin.
AB  - The Huntington's disease gene product, huntingtin, is indispensable for neural
      tube formation, but its role is obscure. We studied neurulation in htt-null
      embryonic stem cells and htt-morpholino zebrafish embryos and found a previously
      unknown, evolutionarily recent function for this ancient protein. We found that
      htt was essential for homotypic interactions between neuroepithelial cells; it
      permitted neurulation and rosette formation by regulating metalloprotease ADAM10
      activity and Ncadherin cleavage. This function was embedded in the N terminus of
      htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10
      inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype
      occurred only with expression of evolutionarily recent htt heterologues from
      deuterostome organisms. Conversely, all of the heterologues that we tested,
      including htt from Drosophila melanogaster and Dictyostelium discoideum,
      exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of
      htt's ancestral function(s), but, in deuterostomes, htt evolved to acquire a
      unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin,
      with implications for brain evolution and development.

PMID- 22466509
TI  - The efficacy of non-directive supportive therapy for adult depression: a meta
      analysis.
AB  - The effects of non-directive supportive therapy (NDST) for adult depression have
      been examined in a considerable number of studies, but no meta-analysis of these
      studies has been conducted. We selected 31 studies on NDST from a comprehensive
      database of trials, examining psychotherapies for adult depression, and conducted
      meta-analyses in which NDST was compared with control groups, other
      psychotherapies and pharmacotherapy. We found that NDST is effective in the
      treatment of depression in adults (g=0.58; 95% CI: 0.45-0.72). NDST was less
      effective than other psychological treatments (differential effect size g=-0.20;
      95% CI: -0.32 to -0.08, p<0.01), but these differences were no longer present
      after controlling for researcher allegiance. We estimated that extra-therapeutic
      factors (those processes operating in waiting-list and care-as-usual controls)
      were responsible for 33.3% of the overall improvement, non-specific factors (the
      effects of NDST compared with control groups) for 49.6%, and specific factors
      (the effects of NDST compared with other therapies) for 17.1%. NDST has a
      considerable effect on symptoms of depression. Most of the effect of therapy for
      adult depression is realized by non-specific factors, and our results suggest
      that the contribution of specific effects is limited at best.

PMID- 22466510
TI  - Computer-based psychological treatments for depression: a systematic review and
      meta-analysis.
AB  - The aim of the paper was to systematically review the literature on computer
      based psychological treatments for depression and conduct a meta-analysis of the
      RCT studies, including examining variables which may effect outcomes. Database
      and hand searches were made using specific search terms and inclusion criteria.
      The review included a total of 40 studies (45 published papers), and 19 RCTs (23
      published papers) were included in a standard meta-analysis. The review describes
      the different computer-based treatments for depression, their design,
      communication types employed: synchronous, asynchronous, and face-to-face (F:F);
      alongside various types and frequency of support delivered. The evidence supports
      their effectiveness and highlights participant satisfaction. However, pertinent
      limitations are noted. Across 19 studies the meta-analysis revealed a moderate
      post-treatment pooled effect size d=.56 (95% confidence interval [CI] -.71, 
      .41), Z=7.48, p<.001). Supported interventions yielded better outcomes, along
      with greater retention. The results reported statistically significant clinical
      improvement and recovery post-treatment. The review and meta-analysis support the
      efficacy and effectiveness of computer-based psychological treatments for
      depression, in diverse settings and with different populations. Further research
      is needed, in particular to investigate the influence of therapist factors in
      supported treatments, the reasons for dropout, and the maintenance of gains post
      treatment.

PMID- 22466511
TI  - Emphysema lung lobe volume reduction: effects on the ipsilateral and
      contralateral lobes.
AB  - OBJECTIVES: To investigate volumetric and density changes in the ipsilateral and
      contralateral lobes following volume reduction of an emphysematous target lobe.
      METHODS: The study included 289 subjects with heterogeneous emphysema, who
      underwent bronchoscopic volume reduction of the most diseased lobe with
      endobronchial valves and 132 untreated controls. Lobar volume and low-attenuation
      relative area (RA) changes post-procedure were measured from computed tomography
      images. Regression analysis (Spearman's rho) was performed to test the
      association between change in the target lobe volume and changes in volume and
      density variables in the other lobes. RESULTS: The target lobe volume at full
      inspiration in the treatment group had a mean reduction of -0.45 L (SE = 0.034, P
      < 0.0001), and was associated with volume increases in the ipsilateral lobe (rho
      = -0.68, P < 0.0001) and contralateral lung (rho = -0.16, P = 0.006), and overall
      reductions in expiratory RA (rho = 0.31, P < 0.0001) and residual volume
      (RV)/total lung capacity (TLC) (rho = 0.13, P = 0.03). CONCLUSIONS: When the
      volume of an emphysematous target lobe is reduced, the volume is redistributed
      primarily to the ipsilateral lobe, with an overall reduction. Image-based changes
      in lobar volumes and densities indicate that target lobe volume reduction is
      associated with statistically significant overall reductions in air trapping,
      consistent with expansion of the healthier lung. KEY POINTS: Computed tomography
      allows assessment of the treatment of emphysema with endobronchial valves. *
      Endobronchial valves can reduce the volume of an emphysematous lung lobe. *
      Compensatory expansion is greater in ipsilateral lobes than in the contralateral
      lung. * Reduced air trapping is measurable by RV/TLC and smaller low attenuation
      area.

PMID- 22466512
TI  - Chronic hypersensitivity pneumonitis: high resolution computed tomography
      patterns and pulmonary function indices as prognostic determinants.
AB  - OBJECTIVES: To investigate high resolution computed tomography (HRCT) and
      pulmonary function indices (PFTs) for determining prognosis in patients with
      chronic fibrotic hypersensitivity pneumonitis (CHP). METHODS: Case records, PFTs
      (FEV(1), FVC and DLco) and HRCTs of ninety-two patients with chronic
      hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two
      observers for total disease extent, ground-glass opacification, fine and coarse
      reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema
      and consolidation. Traction bronchiectasis within each pattern was graded. Using
      Cox proportional hazards regression models the prognostic strength of individual
      HRCT patterns and pulmonary function test variables were determined. RESULTS:
      There were forty two deaths during the study period. Increasing severity of
      traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P <
      0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02,
      P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI
      1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were
      also independent predictors of mortality. In contrast, no individual PFT variable
      was predictive of mortality once HRCT patterns were accounted for. CONCLUSION:
      HRCT patterns, in particular, severity of traction bronchiectasis and extent of
      honeycombing are superior to pulmonary function tests for predicting mortality in
      patients with CHP. KEY POINTS: * HRCT is increasingly used to assess chronic
      fibrotic hypersensitivity pneumonitis. * HRCT patterns are superior to pulmonary
      function tests for predicting mortality. * Extensive traction bronchiectasis
      strongly predicts poor survival in chronic hypersensitivity pneumonitis.

PMID- 22466513
TI  - Quantitative evaluation of MR perfusion imaging using blood pool contrast agent
      in subjects without pulmonary diseases and in patients with pulmonary embolism.
AB  - OBJECTIVE: To assess the feasibility of time-resolved parallel three-dimensional
      magnetic resonance imaging (MRI) for quantitative analysis of pulmonary perfusion
      using a blood pool contrast agent. METHODS: Quantitative perfusion analysis was
      performed using novel software to assess pulmonary blood flow (PBF), pulmonary
      blood volume (PBV) and mean transit time (MTT) in a quantitative manner. RESULTS:
      The evaluation of lung perfusion in the normal subjects showed an increase of
      PBF, PBV ventrally to dorsally (gravitational direction), and the highest values
      at the upper lobe, with a decrease to the middle and lower lobe (isogravitational
      direction). MTT showed no relevant changes in either the gravitational or
      isogravitational directions. In comparison with normally perfused lung areas (in
      diseased patients), the pulmonary embolism (PE) regions showed a significantly
      lower mean PBF (20 +/- 0.6 ml/100 ml/min, normal region 94 +/- 1 ml/100 ml/min; P
      < 0.001), mean PBV (2 +/- 0.1 ml/100 ml, normal region 9.8 +/- 0.1 ml/100 ml; P <
      0.001) and mean MTT (3.8 +/- 0.1 s; normal region 6.3 +/- 0.1; P < 0.001).
      CONCLUSION: Our results demonstrate the feasibility of using time-resolved
      dynamic contrast-enhanced MRI to determine normal range and regional variation of
      pulmonary perfusion and perfusion deficits in patients with PE. KEY POINTS: *
      Recently introduced blood pool contrast agents improve MR evaluation of lung
      perfusion * Regional differences in lung perfusion indicating a gravitational and
      isogravitational dependency. * Focal areas of significantly decreased perfusion
      are detectable in pulmonary embolism.

PMID- 22466514
TI  - Detectability of low and intermediate or high risk prostate cancer with combined
      T2-weighted and diffusion-weighted MRI.
AB  - OBJECTIVES: To evaluate the incremental value of diffusion-weighted imaging (DWI)
      in combination with T2-weighted imaging to detect low (Gleason score, <= 6) and
      intermediate or high risk (Gleason score, >= 7) prostate cancer. METHODS: Fifty
      one patients who underwent MRI before prostatectomy were evaluated. Two readers
      independently scored the probability of tumour in eight regions of prostate on T2
      weighted images (T2WI) and T2WI combined with apparent diffusion coefficient
      (ADC) maps. Data were divided into two groups--low risk and intermediate or high
      risk prostate cancer--and correlated with histopathological results. Diagnostic
      performance parameters, areas under the receiver-operating characteristic curve
      (AUCs) and interreader agreement were calculated. RESULTS: For both readers, AUCs
      of combined T2WI and ADC maps were greater than those of T2WI in intermediate or
      high risk (reader 1, 0.887 vs. 0.859; reader 2, 0.732 vs 0.662, P < 0.05)
      prostate cancers, but not in low risk (reader 1, 0.719 vs 0.725; reader 2, 0.685
      vs. 0.680, P > 0.05) prostate cancers. Weighted kappa value of combined T2WI and
      ADC maps was 0.689. CONCLUSIONS: The addition of DWI to T2-weighted imaging
      improves the accuracy of detecting intermediate or high risk prostate cancers,
      but not for low risk prostate cancer detection. KEY POINTS: * Gleason scores
      influence diagnostic performance of MRI for prostate cancer detection. * Addition
      of DWI does not improve low risk prostate cancer detection. * Combined T2WI and
      DWI may help select intermediate or high risk patients.

PMID- 22466515
TI  - Significance of pulmonary nodules in patients with colorectal cancer.
AB  - OBJECTIVES: Radiographically small pulmonary nodules (PNs) in patients with
      colorectal cancer are troublesome because their discovery raises concern about
      metastases. This study sought to establish the appropriate timing of radiological
      follow-up for PNs detected at initial staging evaluation of colorectal carcinoma
      patients. METHODS: The medical records of 376 consecutive colorectal cancer
      patients who underwent curative surgery and had baseline and follow-up chest X
      rays (CXR) and computed tomography (CT) were reviewed. RESULTS: The study
      included 92 patients who had all CXR and chest CT available for review, at least
      one PN found on baseline imaging, and no synchronous neoplasms. On baseline chest
      CT, these 92 patients had 170 PNs altogether and 77 (45.2 %) of them were greater
      than 5 mm in size. Baseline CXR detected 13 PNs in 12 patients and all but 2 were
      larger than 5 mm. Nodule size greater than 5 mm and irregular margins were
      predictors of nodule growth. The mean doubling time of 24/170 (14.1 %) growing
      PNs was about 4 months. CONCLUSIONS: Our findings suggest that baseline and
      follow-up CXR are pointless, and short-interval CT follow-up is warranted when
      PNs larger than 5 mm with irregular margins are detected on preoperative chest
      CT. KEY POINTS: * Pulmonary nodules in colorectal cancer patients raise concern
      about metastasis. * Baseline and follow-up chest X-ray in colorectal cancer can
      be abandoned. * CT is the best technique for assessing PNs in colorectal cancer.
      * Short-interval CT follow-up advisable for PNs larger than 5 mm with irregular
      margins.

PMID- 22466517
TI  - Does the vigilance-avoidance gazing behavior of children with separation anxiety
      disorder change after cognitive-behavioral therapy?
AB  - Cognitive biases are of interest in understanding the development of anxiety
      disorders. They also play a significant role during psychotherapy, where
      cognitive biases are modified in order to break the vicious cycle responsible for
      maintaining anxiety disorders. In a previous study, the vigilance-avoidance
      pattern was shown in children with separation anxiety disorder (In-Albon et al.
      Journal of Abnormal Child Psychology 38:225-235, 2010). The exhibited avoidance
      pattern may be essential for the maintenance of the anxiety disorder. Therefore,
      in the present study we used eye tracking methodology presenting disorder
      specific pictures to examine possible changes in the vigilance-avoidance pattern
      in 18 children with separation anxiety disorder after cognitive-behavioral
      treatment (CBT) and 13 healthy controls. Results indicated that following
      treatment, the vigilance pattern of children with separation anxiety disorder
      reduced significantly. Thus, the vigilance-avoidance pattern can be modified by
      CBT.

PMID- 22466516
TI  - Emotion dysregulation as a mechanism linking stress exposure to adolescent
      aggressive behavior.
AB  - Exposure to stress is associated with a wide range of internalizing and
      externalizing problems in adolescents, including aggressive behavior. Extant
      research examining mechanisms underlying the associations between stress and
      youth aggression has consistently identified social information processing
      pathways that are disrupted by exposure to violence and increase risk of
      aggressive behavior. In the current study, we use longitudinal data to examine
      emotion dysregulation as a potential mechanism linking a broader range of
      stressful experiences to aggressive behavior in a diverse sample of early
      adolescents (N = 1065). Specifically, we examined the longitudinal associations
      of peer victimization and stressful life events with emotion dysregulation and
      aggressive behavior. Structural equation modeling was used to create latent
      constructs of emotion dysregulation and aggression. Both stressful life events
      and peer victimization predicted subsequent increases in emotion dysregulation
      over a 4-month period. These increases in emotion dysregulation, in turn, were
      associated with increases in aggression over the subsequent 3 months.
      Longitudinal mediation models showed that emotion dysregulation mediated the
      relationship of both peer victimization (z = 2.35, p = 0.019) and stressful life
      events (z = 2.32, p = 0.020) with aggressive behavior. Increasing the use of
      adaptive emotion regulation strategies is an important target for interventions
      aimed at preventing the onset of adolescent aggressive behavior.

PMID- 22466518
TI  - Consultation liaison psychiatry in Greece.

PMID- 22466519
TI  - [Bullying: Prevention and intervention strategies].
AB  - Bullying can be defined as when one (or more) individual engages in aggressive
      behaviour against another individual who seem to be unable to defend himself.
      This action is intentional and persistent and creates great distress and fear.
      There are not specific statistics in Greece but recent researches from EKKE
      showed that one out of four children in Athens have been bullied physically.
      Bullying is a multifaceted and complex problem. Modern psychological perspectives
      emphasize that aggressive and violent behaviours are learned responses to
      frustration. Learning occurs by observing models of such behaviour in the family,
      in the neighbourhood, in school. Ignoring the problem gives a bad example.
      Prevention and intervention strategies should include the family, the school
      personnel and the children. Bullying has negative effects on the physical and
      mental health of the child and it can also cost his life, some kids commit
      suicide. Therefore intervention strategies need to develop in the communities.
      The aim is to create a -physically and psychologically- safe environment.

PMID- 22466520
TI  - [Maternity blues].
AB  - Maternity blues is a transient change of mood that occurs mainly between the 1st
      and 10th day of puerpartum and is characterized by bursts of tears, mild
      depressive mood, anxiety and liability of mood. The frequency of maternity blues
      varies in different studies form 4% to 80%. A number of biological and
      psychosocial parameters have been studied in order to determine their correlation
      with maternity blues. The most well studied biological parameters are
      progesterone and cortizol although their relation with maternity blues has not
      yet been clearly defined. Stress and the emotional state of the woman during
      pregnancy as well as history of mood disorders or maternity blues in a previous
      birth are the psychosocial parameters that are more likely to correlate with the
      occurrence of maternity blues. Most of the authors suggest that information on
      maternity blues and reassurance of the woman are the best way to deal with
      maternity blues both on preventive and therapeutical basis.

PMID- 22466521
TI  - [University entrance of dyslexic students in Greece].
AB  - Students with specific developmental learning disorders (dyslexia) may be
      examined orally in university entrance examination providing they have a
      certificate to that effect from a public child psychiatric or psychoeducational
      centre. The aim of this study was to investigate the success rate of dyslexic
      students in the university entrance examinations. Our hypothesis was, firstly,
      that these students will have the same success rate as other students and
      secondly, that they will mainly enter schools of science or technology. Our
      sample consisted of 420 dyslexic students who had sat for university entrance
      exams in 2006. Data was collected anonymously from Ministry of Education's files
      and consisted of the number of dyslexic students who were examined, their success
      rate, their choice of school and their grade. This data was derived from three
      examination centres in Athens and from five examination centres in an equal
      number of large provincial towns. Results showed that the success rate of
      dyslexic students in university entrance examinations was 39.76%, which was
      statistically lower than that of the general population of candidates which was
      65.36%. Our hypothesis that these students would have a similar university
      entrance rate was not confirmed. Our second hypothesis concerning the preferred
      school of these candidates was confirmed since  the majority of dyslexic students
      chose to study schools of sciences or technology. The dyslexic students' grades
      reveal a similar pattern to those of the general student population in the
      university entrance examinations, as long as these grades are greater than 9 on a
      score from 1-20. However dyslexic students entered technological colleges twice
      as often as the general student population. Our results are representative since
      our data was collected from 25% of university candidates throughout Greece. The
      anonymous nature of our data does not allow us to draw conclusions concerning
      socio-economic status, IQ levels or the quality and quantity of psycho
      educational intervention, which would have led us to a more detailed analysis of
      the parameters leading to success  or failure. Further investigation of the
      academic progress of dyslexic students would give us a more complete view of
      their educational achievements.

PMID- 22466522
TI  - [Liaison child psychiatry and the interpersonal relationships in the context of
      the general child hospital].
AB  - The staff of a big general hospital is a community of people with all the
      alliances and conflicts developing within it. The child psychiatrist works
      primarily with the pediatricians and the nurses but also with other specialized
      people of this community. Pediatricians require a prompt answer to their call,
      clarity of communication and effectiveness. Child psychiatrists complain among
      other things that they are often invited a little before the discharge of the
      child, that their instructions are frequently not followed and that they are not
      informed about the discharge of the patient so to make adequate planning. At the
      hospital prejudices may exist about child psychiatry which have to be overcome by
      the specialist. Meetings between child psychiatrists and pediatricians regarding
      their common patients are helpful in the development of alliances as well as for
      the appreciation of the knowledge and the understanding of patients which a child
      psychiatrist can communicated. Teaching pediatric residents knowledge regarding
      child development elements of psychopathology and of the function of families
      helps them to become acquainted with child psychiatry. The same possibility is
      offered through the daily clinical work of a child psychiatrist. Contact with the
      nursing staff is necessary in order to improve patient care and staff
      cooperation. Relationships developed in the context of consultation liaison child
      psychiatry are frequently modified and under review but can also help to the
      establishment of respect for the work offered by a child psychiatrist.

PMID- 22466523
TI  - [Fibromyalgia and chronic fatigue syndrome in children and adolescents].
AB  - Fibromyalgia and chronic fatigue syndrome are quite common affections in children
      and adolescents. The clinical symptoms include various manifestations such as
      diffuse musculoskeletal pain, feeling of fatigue, depressive symptoms, headache,
      sleep disturbances etc. Physiological, enetic, psychological/psychosocial and
      environmental factors are involved in the pathogenesis of the disorders.
      Fibromyalgia and chronic fatigue syndrome may cause significant deterioration of
      the functional capacity with severe consequences for the child/adolescent's
      family and social life as well as his/her development. There is need for early
      diagnosis, open discussion with the child/adolescent and his/her family and
      therapeutic intervention including drug treatment, physical therapy and
      psychotherapy.

PMID- 22466524
TI  - [Chronic renal insufficiency after long term lithium treatment].
AB  - Lithium is, in the era of evidence-based psychiatry, an efficacious and,
      simultaneously, cost-effective treatment for bipolar disorder, despite the
      existence of alternative mood-stabilizers (antiepileptics, atypical
      antipsychotics). A prerequisite for lithium administration in patients with
      bipolar disorder is the patient 's cooperation, in order to ensure monitoring of
      drug plasma levels as well as thyroid and renal function. Lithium-related renal
      complications include impairment in renal concentrating ability resulting in
      polyuria, increase of plasma creatinine levels and, more rarely, renal
      insufficiency. In this paper we present the case of a patient with bipolar
      disorder, who developed chronic renal insufficiency after 25 years of treatment
      with lithium.

PMID- 22466525
TI  - [Cannibalism and psychopathology].
AB  - Eating members of one's own species is one of the few remaining taboos in modern
      human societies. In humans, aggression cannibalism has been associated with
      mental illness. The objective of this report is to examine the unique set of
      circumstances and characteristics revealing the underlying etiology leading to
      such an act and the type of psychological effect it has for the perpetrator. A
      case report of a patient with paranoid schizophrenia who committed patricide and
      cannibalism is presented. The psychosocial implications of anthropophagy on the
      particular patient management are outlined.

PMID- 22466526
TI  - Gender differences in the effect of weekly working hours on occupational injury
      risk in the United States working population.
AB  - OBJECTIVES: Long working hours can lead to an accumulation in fatigue that may
      increase worker's risk of injury. However, it is not known if this association is
      different for men and women. Our aim was, therefore, to investigate gender
      differences in the effect of weekly working hours on occupational injury risk.
      METHODS: The US National Health Interview Survey is a clustered, stratified,
      cross-sectional sample representative of the US population, collected using in
      household interviews. We pooled seven years of data (2004-2010) comprising 96 915
      employed workers. Annualized injury rates per 100 workers were estimated for men
      and women in categories of weekly working hours (<30, 31-40, 41-50, >50
      hours/week). Additionally, injury risk was predicted using weighted logistic
      regression models by weekly working hour categories, stratified by gender,
      including age, ethnicity, education, type of pay, occupation, body mass index,
      usual sleep duration, and psychological distress as covariates. RESULTS: Of 96
      915 workers, 705 (0.75%) reported an injury in the last 3 months. Injury rates
      were higher among men and increased with increasing working hours for both
      genders. However, results of the adjusted logistic regression model indicated an
      interactive effect of working hours and gender on injury risk [odds ratio (OR)
      1.02, 95% confidence interval (95% CI) 1.00-1.03). Injury risk increased among
      women working 41-50 hours/week (OR 1.51, 95% CI 1.03-2.21) and >50 hours/week (OR
      1.69, 95% CI 1.06-2.70) compared to 31-40 hours/week but not among men.
      CONCLUSIONS: The findings indicate an increase in injury risk with increasing
      working hours among women but not men.

PMID- 22466527
TI  - Rectification in substituted atomic wires: a theoretical insight.
AB  - Recently,  there have been discussions that the giant diode property found
      experimentally in diblock molecular junctions could be enhanced by the many-body
      electron correlation effect beyond the mean field theory. In addition, the effect
      of electron-phonon scattering on an electric current through the diode molecule,
      measured by inelastic tunneling spectroscopy (IETS), was found to be symmetric
      with respect to the voltage sign change even though the current is asymmetric.
      The reason for this behavior is a matter of speculation. In order to clarify
      whether or not this feature is limited to organic molecules in the off-resonant
      tunneling region, we discuss the current asymmetry effect on IETS in the resonant
      region. We introduced heterogeneous atoms into an atomic wire and found that IETS
      becomes asymmetric in this substituted atomic wire case. Our conclusion gives the
      other example of intrinsic differences between organic molecules and metallic
      wires. While the contribution of electron-phonon scattering to IETS is not
      affected by the current asymmetry in the former case, it is affected in the
      latter case. The importance of the contribution of the electron-hole excitation
      to phonon damping in bringing about the current asymmetry effect in IETS in the
      latter case is discussed.

PMID- 22466528
TI  - Diffusion-weighted MR imaging (DWI) in two intradural spinal epidermoid cysts.

PMID- 22466529
TI  - Photosynthesis, photoprotection, and growth of shade-tolerant tropical tree
      seedlings under full sunlight.
AB  - High solar radiation in the tropics is known to cause transient reduction in
      photosystem II (PSII) efficiency and CO(2) assimilation in sun-exposed leaves,
      but little is known how these responses affect the actual growth performance of
      tropical plants. The present study addresses this question. Seedlings of five
      woody neotropical forest species were cultivated under full sunlight and shaded
      conditions. In full sunlight, strong photoinhibition of PSII at midday was
      documented for the late-successional tree species Ormosia macrocalyx and
      Tetragastris panamensis and the understory/forest gap species, Piper reticulatum.
      In leaves of O. macrocalyx, PSII inhibition was accompanied by substantial midday
      depression of net CO(2) assimilation. Leaves of all species had increased pools
      of violaxanthin-cycle pigments. Other features of photoacclimation, such as
      increased Chl a/b ratio and contents of lutein, beta-carotene and tocopherol
      varied. High light caused strong increase of tocopherol in leaves of T.
      panamensis and another late-successional species, Virola surinamensis. O.
      macrocalyx had low contents of tocopherol and UV-absorbing substances. Under full
      sunlight, biomass accumulation was not reduced in seedlings of T. panamensis, P.
      reticulatum, and V. surinamensis, but O. macrocalyx exhibited substantial growth
      inhibition. In the highly shade-tolerant understory species Psychotria marginata,
      full sunlight caused strongly reduced growth of most individuals. However, some
      plants showed relatively high growth rates under full sun approaching those of
      seedlings at 40 % ambient irradiance. It is concluded that shade-tolerant
      tropical tree seedlings can achieve efficient photoacclimation and high growth
      rates in full sunlight.

PMID- 22466530
TI  - Structure and energetics of small iron clusters.
AB  - Electronic properties of Fe(2-10) clusters and their ions are described by an all
      electron ab initio density functional theory computational analysis using the
      Handy's OPTX exchange and the gradient-corrected correlation functional of
      Perdew, Burke and Ernzerhof with a triple-zeta valence basis set plus
      polarization functions. Ground state structures, magnetic moments, dissociation
      energies, binding energies, IR vibrational spectra, vertical and adiabatic
      ionization energies, and electron affinities are reported. Two possible states
      for Fe(2) which are separated by 81.54 meV are described as possible Fe(2), while
      the septet (ground state) yields an accurate bond distance (error of 0.02 A); the
      nonet yields a precise vibrational frequency (error of 10.1 cm(-1)). Fe(2)
      binding energy (0.05 eV/atom error) more closely resembles experimental data than
      any other previously reported computational methods. In addition, the Fe(6) is
      found to be the most stable cluster within our set being analyzed.

PMID- 22466531
TI  - Spin state dependence of electrical conductivity of spin crossover materials.
AB  - We studied the spin state dependence of the electrical conductivity of the spin
      crossover compound [Fe(Htrz)(2)(trz)](BF(4)) (Htrz = 1H-1,2,4-triazole) by means
      of dc electrical measurements. The low spin state is characterized by higher
      conductance and lower thermal activation energy of the conductivity, when
      compared to the high spin state.

PMID- 22466532
TI  - Antecedents of Chinese parents' autonomy support and psychological control: the
      interplay between parents' self-development socialization goals and adolescents'
      school performance.
AB  - Despite ample evidence for the benefits of parental autonomy support and the
      harms of parental psychological control to Chinese adolescents' well-being,
      little is known about what foreshadows these parenting behaviors among Chinese
      parents. The current research addressed this gap in the literature. It tested the
      hypothesis that parents' endorsement of self-development socialization goals
      (i.e., regarding a positive sense of self in terms of holding optimistic
      attitudes toward oneself, feeling autonomous in one's actions, and establishing
      one's independence from others, as important for adolescents to develop) and
      adolescents' school performance may interact to predict parental autonomy support
      and psychological control in urban China. Three hundred and forty-one Chinese
      seventh graders (mean age = 13.30 years, 58 % female) and their parents (186
      mothers and 155 fathers) participated. Parents reported on their own and their
      spouses' endorsement of self-development socialization goals; adolescents
      reported on parental autonomy support and psychological control; and adolescents'
      grades were obtained from school records. Significant interactions were found
      between parents' socialization goals and adolescents' grades in predicting
      parenting behaviors. When adolescents were doing well at school, the stronger
      parents' endorsement of self-development socialization goals, the greater their
      autonomy support and the lesser their psychological control; when adolescents
      were doing poorly at school, regardless of parents' socialization goals, their
      autonomy support was relatively low and their psychological control was
      relatively high. These findings highlight a tension between parental concerns
      over adolescents' self-development and academic success, which needs to be
      resolved to promote autonomy support and prevent psychological control among
      urban Chinese parents.

PMID- 22466533
TI  - [Background diseases in thyroid cancer].
AB  - The study of thyroid cancer background diseases in hospitals of Republic of
      Armenia was carried out. 529 cases of primary thyroid cancer were studied from
      1999 to 2011. It was found that in women, concomitant thyroid pathology is more
      common than in men (p<0.05). The morphological verification of any nodules in the
      thyroid gland is necessary. Thyroid cancer can occur on the background of benign
      thyroid diseases, but this is no reason for regarding these as a precancerous
      conditions. According to the results of this study, the incidence of "hidden"
      carcinomas is the same, as revealed on the background of benign Thyroid diseases
      and without the benign nodes. One of the most important prognostic factors for
      long-term survival of patients with thyroid cancer is a timely diagnosis. Early
      detection of tumors and the exact differential diagnosis of benign nodes with
      carcinomas can eliminate the malignant process in the initial stages of its
      development. In our material there was no case of a combination of thyrotoxic
      Goiter with thyroid cancer.

PMID- 22466534
TI  - Role of estrogens in pathogenesis of age-related disease in women of menopausal 
      age.
AB  - The aim of our study was to determine the influence of estrogen on the intensity
      of oxidative metabolism in women of reproductive and menopausal age. Two groups
      of women - less than 45 years old (reproductive age) and more than 45 years old
      (menopausal age) were investigated. In each group we investigated the estradiole,
      fibrinogen, ALT, oxygen (O(2)(-)) and lipid (LOO.) reactive spesies, NO content,
      antioxidant enzymes (SOD, catalase, GR) activity. It was reviealed nondirect
      corelation between development of inflammation, hypoxia and estrogen content in
      the blood of women without genetic predisponce to alterations of lipid
      metabolism. Subsequently in reproductive age they are developed usually against
      hypoestrogenomia; however the physiological reduction in estrogen levels during
      menopause by itself contributes to impairment of metabolism and intensification
      of inflammation (inflammatory markers CPR, ALT), oxidative stress (O(2)(-),
      LOO.), hipoxia (HBNO) and all related compititions (increase vascular resistence,
      disorders in oxygen suplay in tissue and hypoxic compititions of there
      metabolism). All this may cause, postmenopausal hypertension, hart ischemis
      disease, impaired hepatic beta-oxidation of fatty acids and hepathosteatosis. In
      women with genetic predisponce to dislipidemia the estrogen-related factors are
      less important in pathogenesis of age-related diseases.

PMID- 22466535
TI  - [Immune system disorders and their correction in critically ill patients with
      toxic and hypoxic encephalopathy].
AB  - In this article there are materials, which were received in the process of
      treatment of 69 patients with azaleptin (leponeks) acute severe poisonings. The
      immunologic research has shown that the first phase of acute poisonings in
      patients with toxicohypoxic encephalopathy is accompanied by severe immune
      alterations. The alterations of proinflammation and antiinflammation cytokines
      have been investigated and its increase has not been revealed. It was shown, that
      the employment of citoflavin in intensive therapy of acute poisonings leads to
      decrease of the level of immunosupression.

PMID- 22466536
TI  - [Use of cytoflavin into the complex intensive therapy of acute cerebral
      insufficiency caused by poisoning].
AB  - In the result of treatment of 147 patients with toxic acute brain insufficiency
      were revealed that the employment of citoflavin (20 ml with 400 ml 5% glucosae
      twice a day) in 7 days intensive therapy of acute brain insufficiency leaded to
      decrease of hypoxic brain damages and intensity of brain depression, what was
      revealed in improvement of brain bioelectric activity. Rehabilitation of central
      nervous system regulation function and life-support systems leaded to quick
      rehabilitation of respiratory part of oxygen transport. These changes in acute
      period leaded to quick reparation of cognitive-mnestic functions and social
      adaptation. The employment of citoflavin leaded to improvement of clinic of
      toxicohypoxic encephalopathy and to decrease of secondary lung complications
      (decrease of coma-period from 45,3 +/- 8,2 to 27,7 +/- 6,9 hours; decrease of
      secondary lung complications from 72,7% to 35,9%).

PMID- 22466537
TI  - Reproducibility and diagnostic value of E100 event recorder for patients with
      complains on heart arrhythmias and no changes on multiple routine ECGs and 24
      hour holter monitoring.
AB  - Aim of the study was to assess reproducibility and diagnostic value of E100 event
      recorder for patients with complains on heart arrhythmias and no abnormalities on
      multiple routine ECGs and/or 24-hour Holter ECG monitoring and the second one, an
      assessment of adherence and attitude of patients to the E100 event recorder,
      dependent on the results of self- assessment questionnaires. 24 patients with
      complains on heart arrhythmias were included in the study. All the patients were
      provided with the REKA E100 event monitors for 5 +/- 2 days and self-assessment
      questionnaires to assess level of adherence and attitude of patients to the E100
      event recorder. E100 event recorders revealed junctional rhythm (n=2), AV nodal
      reentrant tachycardia (n=2), extrasystolic arrhythmias (n=10), atrial
      fibrillation (n=2), WPW syndrome (n=4), ventricular tachycardia (n=1), sinus
      tachycardia (n=7) and complete AV block (n=1). Majority of patients consider
      device as easy to use, comfortable and safe. In comparison with multiple routine
      ECGs and 24-hour Holter ECG monitoring, E100 event recorders showed higher
      reproducibility and efficacy for detecting and interpreting heart arrhythmias.

PMID- 22466538
TI  - [HOMA-IR in patients with chronic hepatitis C].
AB  - The aim of investigation was to study the frequency of IR in type of viral
      hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis.
      130 patients were investigated: 20 with acute hepatitis C; 38 with chronic
      hepatitis C; 72 with cirrhosis: among them 10 with Stage A, 14 with Stage B and
      48 with Stage C. Also we used 30 healthy people as the controls. The study
      demonstrates significant changes of insulin, glucose, HOMA-IR type of viral
      hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis.
      In patients with liver cirrhosis levels of HOMA-IR is higher than in patients
      with chronic hepatitis C. In patients with acute hepatitis C levels of HOMA-IR
      was normal as in the control group. The results showed that various types of
      chronic viral hepatitis C and stages of cirrhosis set to increase HOMA-IR versus
      the controls., which were the most prominent in cases of severe hepatic lesion,
      which indicates that insulin resistance is a frequent companion of CHC.

PMID- 22466539
TI  - [Epidemiology of meningococcal infection in Georgia].
AB  - Epidemiology of meningococcal infection in Georgia was studied for 2009-2011. As
      the official surveillance data shows, morbidity with the infection is
      characterized by a downward trend. During the analyzed period the morbidity level
      declined by 2,4 times. The average incidence rate for the period composed 0,95 +/
      0,12 per 100 000 population. The infection is unequally spread throughout the
      country. High incidence is indicated in Tbilisi city and the regions: Ajara and
      Kvemo Kartli. Children are the most vulnerable population. 81,3% of all the cases
      fell on the children' population. High incidence rate in children of the age
      under 1 year is especially alarming, composing 11,52 per 100 000 population.
      Irrespective of the downward trend meningococcal infection in Georgia remains as
      a severe disease, high level of lethal outcome (lethality 18,6+/-3,0%) is the
      confirmation of that. Lethality is even higher in small children under 1 year -
      27,7 +/- 7,4%. The study of the isolated N. meningitides from patients with
      meningococcal meningitides as well as with meningococcemia showed that N.
      meningitides of the serosgoups B and C are being circulated in Georgia.
      Epidemiological investigation of the infection foci in terms of medical
      examination of contact persons of the cases indicated that the causative agents
      of the same serogroups are also widely circulated among contact subjects. Along
      of the passive surveillance data on the meningococcal disease, results of active
      investigation of epidemiological foci of the infection may serve as valuable
      information for planning of specific prevention measures against the infection.

PMID- 22466540
TI  - [Health of Tbilisi underground metro workers under modern social and economic
      conditions in Georgia].
AB  - The aim of the research was to study the health of Tbilisi underground metro
      workers under modern social-economic conditions in Georgia. Occupational
      pathology of the cardiovascular, digestive systems, psycho-emotional state, osteo
      articular apparatus were found statistically significant among the basic group
      workers, more frequently in comparing with a control group without professional
      contact to major harmful factors (vibration, noise, meteorological conditions,
      air pollution environment with dust and toxic gases p<0.001). On the basis of
      hygienic-clinical relationship between working conditions and a state of health
      are established.

PMID- 22466541
TI  - [Saturin - effective vegetative remedy in treatment of type 2 diabetes mellitus].
AB  - A chemical investigation of plant Satureja hortensis L. - garden savory (GS) has
      been carried out. It is established that the GS is rich in phenolic compounds.
      Flavonoids apigenin, luteolin, cinaroside, luteolin-glucuronide, luteolin
      rutinoside, isoroifolin and phenylcarbonic acids - chlorogenic acid and
      rosmarinic acid were isolated from the leaves of the plant. The total content of
      flavonoids and phenylcarbonic acids in GS is 1,6-1,7%. The leaves of GS contain
      up to 1% essential oil consisting mainly of thymol and methyl carvacrol. Dry
      aqueous extract of GS leaves, which retains the full range of substances of raw
      plant material has been obtained. Pharmacological investigation of the GS extract
      was carried out on intact animals and animals with experimental alloxan diabetes.
      Antidiabetic Arfasetine was chosen as a reference drug. The study revealed that
      the GS extract exhibits hypoglycemic activity significantly reducing blood sugar
      levels and is safe in the long run. Drug dosage form named saturin - capsules
      containing 0,33 g of dried aqueous extract of GS leaves, has been developed.
      Clinical trials of Saturin confirmed its effiacy in diabetes mellitus type 2. The
      drug is registered by the Ministry of Health, Labour and Social Welfare of
      Georgia (Registration Certificate No003658) and approved for use in type 2
      diabetes either independently or in combination with other hypoglycemic agents.
      Saturin is manufactured at the Experimental and Production Facility of the
      Institute of Pharmacochemistry.

PMID- 22466542
TI  - Characterization of oral squamous cell cancer in nude mice model.
AB  - Most common type of head and neck malignant tumors is squamous cell carcinoma
      reaching 3% of all human cancers. Oral squamous cell carcinoma (OSCC) has
      tendency of increasing incidence and mortality worldwide with an overall 5 year
      survival rate of <60%. In order to explore this disease, different in vivo mouse
      models have been introduced. In this study we analyzed clinical and morphological
      characteristics of OSCC in vivo nude mouse model. 80% of mice which were injected
      with human oral squamous cancer cells developed orthotopic tumors with the mean
      volume of 146 mm(3), from which 62% exhibited metastatic spread. Morphology of
      the cancer tissue was characterized with invasive phenotype and inflammation.
      Proliferation activity rate of orthotopicly grown tumors were 55,7 +/- 4,7
      mitotic cells/optical field and displayed weakly developed vascular network. OSCC
      in vivo orthotopic nude mouse model can mimic pathological and clinical picture
      of the malignant disease and may be effectively used in oncology research.

PMID- 22466543
TI  - [Effect of ascorbic acid (vitamin C) on the EPR spectra from the black and red
      hair].
AB  - The EPR spectra of melanin's free radicals in natural black and red hair have
      been investigated. It is show that the EPR spectrum of black hair is slightly
      asymmetric singlet with g=2,0035 and DeltaH=0,5 mTl. The EPR spectrum of red hair
      with g=2,0053 differs from the spectrum of black hair. Under the influence of
      visible (blue with lambda(max)=450 nm) in both types of hair (black and red), the
      protoinduced free radicals appear, which indicates an increase in the intensity
      of already existing EPR spectrum of hair. It should be noted that the EPR spectra
      of red hair from various donors are different. The antioxidant ascorbic acid has
      the different effect on the photoinduced free radicals. In particular, in the
      case of black hair, the concentration of photoinduced free radicals is slightly
      reduced, whereas in red hair, the disappearance of the triplet in the spectrum is
      observed, and at the same time, the spectrum becomes a singlet, the intensity of
      which increases sharply.

PMID- 22466544
TI  - Analysis of consumer demand for herbal medicine in the Republic of Armenia.
AB  - Herbal medicines nowadays tend to gain more and more popularity among health care
      providers and drugstore customers, as well. Current study has been an effort to
      explore the attitudes and customer behavior of drug consumers in Yerevan,
      Armenia. It is a cross-sectional descriptive study in nature an has no hypothesis
      set and does not claim to have produced statistically significant generalizable
      results. However, it is a valuable start point for further investigations with
      presumably quantitative statistical analysis methods. Some four districts of
      Yerevan out of twelve were randomly selected with subsequent random selection of
      proportionately adequate number of drugstores, where the interviewers approached
      every 4th customer with the request to answer the questionnaire that they had
      previously developed and tested in three randomly chosen non-target drugstores
      from one randomly chosen non-target district. Data were collected by filling
      paper forms followed by entry and processing using SPSS 11.0 for Windows. The
      results of the study demonstrate that some link exist between customers'
      appreciation of herbal drugs as safe and effective and their level of education.
      Another dimension discovered, was that university students appeared to be the
      most satisfied with the affordability of herbal medicines.

PMID- 22466545
TI  - Effect of the anchor in polyethylene glycol-lipids on the transfection activity
      of PEGylated cationic liposomes encapsulating DNA.
AB  - The use of polyethylene glycol (PEG)-modified lipids (PEG-lipids) as a component
      of cationic liposomes impairs the cytoplasmic delivery of the encapsulated cargos
      by reducing endosomal escape. While this results in a loss of gene expression of
      encapsulated plasmid DNA, PEG-modification is useful in that it permits the
      formation of small, stabilized particles. In the present study, the dilemma
      associated with the use of PEG was overcome by modifying liposomes with
      stearylated INF7 (STR-INF7), a membrane fusion-independent destabilizer of
      endosomes, and substituting hydrophobic lipid-anchors in the PEG-lipid. The
      cationic liposomes modified with a series of PEG-lipids showed a drastically
      impaired transgene expression. However, the incorporation of STR-INF7 recovered
      the gene expression, and this was found to be mainly dependent on the type of PEG
      lipid-anchor used. Of note, the fold increase in transfection activity was
      highest in cholesterol-anchored PEG (>100-fold), whose enhanced endosomal escape
      was followed by imaging techniques. These data suggest that the structure of
      lipid-anchors in PEG affects the action of the peptides for inducing of endosomal
      escape.

PMID- 22466546
TI  - Astragalus extract alleviates nerve injury after cerebral ischemia by improving
      energy metabolism and inhibiting apoptosis.
AB  - This aim of this study was to explore the effects and molecular mechanisms of
      Astragalus extract against cerebral ischemia injury through the energy metabolism
      and apoptosis pathways of c-Jun N-terminal kinase (JNK) signal transduction.
      After the bilateral common carotid artery of C57BL/6 mice was occluded for 20 min
      followed by 1-h reperfusion, the ATP content, total adenine nucleotides (TAN),
      energy charge (EC), and sodium potassium ATPase (Na(+)-K(+)-ATPase) activity were
      decreased markedly in brain tissues. Astragalus extract markedly increased the
      ATP and ADP levels, EC value, and Na(+)-K(+)-ATPase activity. Twenty-four and 48
      h after reperfusion, the neurocyte survival rate decreased and apoptosis rate
      increased, while the expression of phosphorylated JNK1/2, cytochrome c (Cyt C),
      and cysteine aspartic acid-specific protease (caspase)-9 and -3 were
      significantly enhanced in brain tissues. Astragalus extract significantly
      increased neurocyte survival and decreased the apoptosis rate as well as down
      regulated the expression of p-JNK1/2, Cyt C, caspase-9, and caspase-3. These
      results suggest that Astragalus extract has neuroprotective effects against nerve
      injury after cerebral ischemia-reperfusion, and the underlying mechanism may be
      associated with improved cellular energy metabolism, inhibition of JNK signal
      transduction pathway activation, and then suppression of the mitochondrial
      apoptosis pathway.

PMID- 22466547
TI  - Single-walled carbon nanotubes downregulate stress-responsive genes in human
      respiratory tract cells.
AB  - Carbon nanotubes (CNTs) are currently key promising materials of nanotechnology.
      However, elucidation of the possible effects of CNTs on the respiratory tract is
      urgently needed. The present study aimed to clarify the effect of single-walled
      CNTs (SWCNTs) on the expression of stress-responsive genes, using primary
      cultured normal human bronchial epithelial (NHBE), diseased HBE (DHBE) cells, and
      the human carcinoma cell lines A549 and FaDu. Purified SWCNTs were applied at
      concentrations of 0.1 or 1.0 mg/mL for 6 h, and a polymerase chain reaction (PCR)
      array was conducted to examine 84 stress-responsive genes. NHBE cell exposure to
      SWCNTs resulted in global downregulation of genes involved in inflammation,
      oxidative stress, and apoptosis. Further analysis using DHBE cells and carcinoma
      cell lines indicated a similar trend, although differences in sensitivity were
      observed. Downregulation of stress-responsive genes may be involved in the
      mechanism by which stress response protects against lung injury.

PMID- 22466548
TI  - Prooxidant-induced glutathione antioxidant response in vitro and in vivo: a
      comparative study between schisandrin B and curcumin.
AB  - We investigated whether two naturally-occurring prooxidants, namely, schisandrin
      B (Sch B) and curcumin, and a synthetic prooxidant, menadione, can invariably
      elicit cyto/hepatoprotective responses against oxidant-induced injury. Results
      showed that (-)Sch B (a potent enantiomer of Sch B, 15 MUM), curcumin (7.5 MUM)
      and menadione (2 MUM) induced a similar extent of reactive oxygen species
      production in AML12 cells. The relative potencies of cytoprotection in vitro were
      in a descending order of curcumin>menadione>(-)Sch B, which were parallel to the
      extent of stimulation in cellular reduced glutathione level. We further examined
      their hepatoprotection in vivo. Pretreatment with Sch B (800 mg/kg) and curcumin
      (737 mg/kg), but not menadione (344 mg/kg), protected against CCl(4) toxicity,
      with the degree of protection afforded by Sch B being much larger than that of
      curcumin. The attenuated hepatoprotection afforded by curcumin may be attributed
      to its low bioavailability in vivo. This postulation is supported by the findings
      that intraperitoneal injections of Sch B (400 mg/kg) and curcumin (368 mg/kg) and
      the long term, low dose treatment with Sch B (20 mg/kg/d*15) and curcumin (18
      mg/kg/d*15) induced glutathione antioxidant response and hepatoprotection to
      similar extents in vivo. The inability of menadione to induce hepatoprotection
      may be related to its extensive intestinal metabolism and/or hepatotoxicity.
      Taken together, prooxidants can invariably induce the glutathione antioxidant
      response and confer cytoprotection in vitro. Whether or not the prooxidant can
      produce a similar response in vivo would depend on its bioavailability and
      potential toxic effect.

PMID- 22466549
TI  - Effect of lipopolysaccharide on the xenobiotic-induced expression and activity of
      hepatic cytochrome P450 in mice.
AB  - Infection-associated inflammation can alter the expression levels and functions
      of cytochrome P450s (CYPs). Cyp gene expression is regulated by the activation of
      several nuclear receptors, including pregnane X receptor (PXR), constitutive
      androstane receptor (CAR), and aryl hydrocarbon receptor (AhR). These receptors
      can be activated by xenobiotics, including medicines. Here, to study the
      xenobiotic-induced fluctuations in CYP during inflammation, we examined the
      effect of lipopolysaccharide (LPS) treatment on the level of mRNAs encoding
      hepatic CYPs induced by xenobiotic-activated nuclear receptors, in mice. Both the
      mRNA induction of Cyp genes and the metabolic activities of CYP proteins were
      examined. LPS treatment caused a significant decrease in the induced expression
      of the mRNAs for Cyp3a11, 2c29, 2c55, and 1a2, but not for Cyp2b10. To assess the
      CYP enzymatic activities, CYP3A-mediated testosterone 6beta-hydroxylation and the
      intrinsic clearance (CL(int)) of nifedipine in liver microsomes were measured in
      mice treated with the xenobiotic pregnenolone-16alpha-carbonitrile (PCN) with or
      without LPS administration. Both assays revealed that the CYP3A activity, which
      was induced by PCN, declined significantly after LPS treatment, and this decline
      correlated with the Cyp3a11 mRNA level. In addition, we found that the mRNAs for
      interleukin (IL)-1beta and tumor necrosis factor (TNF) alpha were increased after
      treatment with LPS plus xenobiotics. Our findings demonstrated that LPS treatment
      reduces the PXR- and AhR-mediated, and possibly CAR-mediated Cyp gene expression
      and further suggest that these decreases are dependent on inflammatory cytokines
      in the liver.

PMID- 22466550
TI  - Effects of memantine, an N-methyl-D-aspartate receptor antagonist, on fatigue and
      neuronal brain damage in a rat model of combined (physical and mental) fatigue.
AB  - Most of the fatigue in everyday life is a combination of physical and mental
      fatigue. Recently, an animal model of combined fatigue was designed by housing
      rats in a cage filled with water. We have previously hypothesized that mental
      fatigue is caused partly by neuronal brain damage through the activation of N
      methyl-D-aspartate (NMDA) receptors by quinolinic acid (QUIN), a metabolite of
      tryptophan (TRP). Therefore, we investigated whether the same mechanism also
      participates in combined fatigue. Rats were housed for 5 d under water-immersed
      conditions, and the extent of fatigue was evaluated by a weight-loaded forced
      swimming test. The swimming time of the water-immersed group was shorter than
      that of the control group, indicating that rats were fatigued by water-immersion.
      However, unexpectedly, the blood and brain levels of QUIN in the water-immersed
      group were lower than those of the control group. QUIN levels in both the blood
      and brains of a food-restricted nonimmersed group, where body weight was matched
      with the water-immersed group, were also decreased, suggesting that decreased
      QUIN in the water-immersed group originated from a reduced intake of TRP
      containing food. On the other hand, hippocampal neuronal damage was shown in the
      water-immersed group, similar to that seen in other fatigue models where QUIN
      increased. Memantine, an NMDA receptor antagonist, inhibited not only the
      reduction in swimming times but also the neuronal damage induced by water
      immersion. These results suggest that neuronal brain damage by an endogenous NMDA
      receptor agonist other than QUIN participates in combined fatigue by water
      immersion.

PMID- 22466551
TI  - Influence of concomitant antiepileptic drugs on plasma lamotrigine concentration
      in adult Japanese epilepsy patients.
AB  - Lamotrigine (LTG) is an antiepileptic drug (AED) that was approved in Japan in
      2008. We evaluated the influence of AEDs that induce hepatic enzymes (including
      phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ)), valproic acid (VPA),
      and various combinations of these drugs, on plasma LTG concentration in adult
      Japanese epilepsy patients. A total of 621 patients (mean age 34.4+/-11.8 years)
      were evaluated retrospectively. We calculated the concentration to dose ratio (CD
      ratio) for LTG with different AED regimens, and employed multiple regression
      analysis to determine factors influencing the LTG concentration. There was a
      linear correlation between the dose and concentration of LTG in patients treated
      with LTG (group I), LTG+VPA (group II), LTG+inducers (group III), or
      LTG+VPA+inducers (group IV). The mean CD ratio of patients on LTG monotherapy was
      1.43+/-0.4 (MUg/mL)/(mg/kg). When LTG was combined with VPA, the CD ratio
      increased about 2.2-fold, but there was no significant correlation between the CD
      ratio and VPA concentration. The mean CD ratios calculated in patients receiving
      LTG+PHT, LTG+PB, and LTG+CBZ were 0.56, 0.84, and 0.91, respectively. Addition of
      PHT significantly reduced the CD ratio in a concentration-dependent manner, in
      comparison with PB and CBZ (p<0.005 and p<0.001, respectively). Stepwise multiple
      regression analysis showed that the coefficient of determination of groups I, II,
      III, and IV were 0.94, 0.94, 0.90, and 0.91, respectively. In the clinical
      setting, these findings can help to estimate LTG concentrations and predict the
      inducing or inhibiting effects of concomitant AEDs.

PMID- 22466552
TI  - Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of
      oxidative stress in rabbits.
AB  - Tetomilast was originally identified as a potent inhibitor of superoxide
      production in human neutrophils, and is of interest because it may relieve
      oxidative stress related to chronic obstructive pulmonary disease (COPD). Our
      objective was to determine whether tetomilast effectively protects against the
      development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits.
      Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast
      n=18). The rabbits were once daily orally administered vehicle solution or
      tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared
      pulmonary function, inflammatory cell infiltration, oxidative stress, and the
      incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced
      increases in the incidence of apoptosis and the production of 8-hydroxy
      deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with
      tetomilast showed significantly less mean linear intercept and significantly
      better pulmonary function than rabbits administered PPE alone. Tetomilast may
      inhibit the development of emphysema by attenuating pulmonary inflammation and
      apoptosis caused by PPE-induced oxidative stress.

PMID- 22466553
TI  - In vitro antimetastatic activity of koetjapic acid against breast cancer cells.
AB  - Breast cancer is the most common cancer in women, and it can metastasize very
      rapidly. Tumor metastasis is the primary cause of cancer deaths. In the present
      study, we investigated the capability of koetjapic acid, a natural triterpene, in
      the induction of apoptosis and the inhibition of metastasis in the breast cancer
      cell line (MCF 7). The effects of koetjapic acid against 4 steps of metastasis
      have been assessed, including cell survival, clonogenicity, migration and
      invasion. Koetjapic acid exhibited cytotoxic activity against MCF 7 cells with an
      IC(50) of 68.88+/-6.075 MUg/mL. The mechanism of cell death was confirmed due to
      the induction of apoptosis machineries; early and late apoptosis-related changes
      were detected, including the stimulation of caspase 3/7 activities, apoptosis
      related morphological changes such as membrane blebbing, chromatin condensation
      and DNA fragmentation. A mitochondrial apoptosis pathway was found to be involved
      in koetjapic acid-induced cell death induction. Moreover, at a sub-toxic dose (15
      MUg/mL), Koetjapic acid inhibited cell migration and invasion significantly.
      Finally, koetjapic acid inhibited the colony formation properties of MCF 7
      significantly. These results indicate that koetjapic acid possesses significant
      antitumor and antimetastatic effects, and warrants further investigation.

PMID- 22466554
TI  - In vitro and in vivo antimicrobial effect of photodynamic therapy using a highly
      pure chlorin e6 against Staphylococcus aureus Xen29.
AB  - Photodynamic therapy (PDT) has been recommended as an alternative therapy for
      various diseases including microbial infection. Recently, we developed a new
      method for the preparation of highly pure chlorin e(6) (Ce(6)), which has been
      widely used as a second-generation photosensitizer. PDT using Ce(6) was very
      effective for inhibition of in vitro growth of several bacterial strains. To
      clarify a possibility for its clinical application, in this study, we examined in
      vitro and in vivo antimicrobial effects of Ce(6)-mediated PDT in mice model of
      skin infection of Staphylococcus aureus Xen29. Inhibition zone analysis and
      colony forming unit (CFU) count revealed that Ce(6)-mediated PDT inhibited
      effectively in vitro bacterial growth. In addition, biofilm formation ability of
      S. aureus Xen29 was decreased by Ce(6)-mediated PDT. In vivo experiment, mice
      receiving Ce(6)-mediated PDT exhibited less intensity of bioluminescent signal,
      showing significant inhibition of bacterial growth. Furthermore, in
      histopathological examination, marked neutrophilic infiltration and massive
      bacterial colonies were seen in control mice and mice receiving laser or Ce(6)
      alone, but not in mice treated with PDT. These results suggest that PDT using
      Ce(6) extracted by our new method can be clinically useful against bacterial
      infectious diseases.

PMID- 22466555
TI  - Hydroxysafflor yellow A alleviates early inflammatory response of bleomycin
      induced mice lung injury.
AB  - Hydroxysafflor yellow A (HSYA) is an effective ingredient of Chinese herb
      Carthamus tinctorius L. The aim of this study was to evaluate the protective
      effect of HSYA on inflammatory phase of bleomycin-induced pulmonary injury in
      mice. Three doses of HSYA (26.7, 40, 60 mg/kg/d) were intraperitoneally injected
      to mice consecutively for 1 week after bleomycin administration. It was found
      that HSYA attenuated the loss in body weight, the increase of myeloperoxidase
      activity and pathologic changes of pulmonary inflammation caused by bleomycin.
      Treatment with HSYA also alleviated bleomycin-induced increase of mRNA level of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and transforming growth
      factor (TGF)-beta1 in lung homogenates. Moreover HSYA inhibited the increased
      activation of nuclear factor (NF)-kappaB and phosphorylation of p38 mitogen
      activated protein kinases (MAPK) in lung tissue. These findings demonstrated that
      HSYA had protective effect on bleomycin-induced lung inflammatory response.

PMID- 22466556
TI  - Evaluation of the mechanism of skin enhancing surfactants on the biomembrane of
      shed snake skin.
AB  - The aim of the present work was to investigate the effects of different
      surfactants at various concentrations as a skin penetration enhancer through the
      biomembrane of the shed skin of Naja kaouthia. Additionally, the enhancer
      mechanism(s) of each class of surfactants were evaluated using physical
      characterization techniques, such as scanning electron microscopy (SEM),
      attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy,
      and small and wide angle X-ray scattering (SWAXS). Our results showed that skin
      permeability increased with increasing concentrations of surfactants and the
      degree of increase was higher for the model hydrophilic permeant, deuterium
      dioxide (D(2)O), than the lipophilic permeant, ketoprofen (KP). Ionic
      surfactants, sodium lauryl sulfate (SLS) and cetyl trimethyl ammonium bromide
      (CTAB), demonstrated higher enhancement ability than the polyoxyethylene (20)
      sorbitan mono-oleate (Tween 80) non-ionic surfactant, which was consistent with
      the results from physical characterization studies. Increasing amounts of
      permeated drug resulted in an increase in membrane interactions. From our
      observations, it can be assumed that SLS and CTAB can be localized inside the
      biomembrane and thereby enhance drug permeation mainly through interactions with
      intercellular lipids in the stratum corneum (SC) and the creation of a perturbed
      microenvironment among lipid alkyl chains and polar head groups.

PMID- 22466557
TI  - High dose dietary pyridoxine induces T-helper type 1 polarization and decreases
      contact hypersensitivity response to fluorescein isothiocyanate in mice.
AB  - Pyridoxine (vitamin B(6)) is commonly used as a dietary supplement and beneficial
      effects of it are expected. However, excess ingestion of pyridoxine has been
      shown to cause a severe sensory neuropathy in humans and experimental animals. We
      have been studying the linkage between the nervous and immune systems using a
      fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse
      model. We have found that activation of transient receptor potential ankyrin 1
      (TRPA1), which is expressed on sensory neurons, enhances skin sensitization to
      FITC. Another feature of FITC-induced CHS is its dependence on T helper 2 (Th2)
      type responses. We hypothesized that the excess intake of pyridoxine may affect
      sensitization to FITC and influence helper T-cell polarization. We examined FITC
      induced CHS in BALB/c mice fed a diet containing excess pyridoxine (120 mg/kg
      diet) for 3 weeks. We found that mice fed on the excess-pyridoxine diet exhibited
      a lower response as to FITC-induced CHS compared with ones fed on a diet with a
      standard pyridoxine content (6.0 mg/kg diet). Moreover, the interferon (IFN)
      gamma/interleukin (IL)-4 ratio produced by draining lymph node cells was
      significantly higher with the excess-pyridoxine diet. This suggested that the
      cytokine balance was shifted toward Th1 with the excess-pyridoxine diet.
      Consistently, Th1-dependent oxazolone-induced CHS was enhanced with the excess
      pyridoxine diet. These results suggested that an excess pyridoxine intake
      actively influences the immune system by altering helper T cell polarization.

PMID- 22466559
TI  - Combination therapy of surgical tumor resection with implantation of a hydrogel
      containing camptothecin-loaded poly(lactic-co-glycolic acid) microspheres in a C6
      rat glioma model.
AB  - We have developed a drug-loaded poly(lactic-co-glycolic acid) (PLGA) microsphere
      containing thermoreversible gelation polymer (TGP) (drug/PLGA/TGP) formulation as
      a novel device for implantation after surgical glioma resection. TGP is a
      thermosensitive polymer that is a gel at body temperature and a sol at room
      temperature. When a drug/PLGA/TGP formulation is injected into a target site,
      PLGA microspheres in TGP gel localize at the injection site and do not diffuse
      across the entire brain tissue, and thus, sustained drug release from the PLGA
      microspheres at the target site is expected. Using in vivo imaging, we confirmed
      that the implantation of indocyanine green (ICG)/PLGA/TGP formulation exhibited a
      stronger localization of ICG at the injection site 28 d after injection compared
      with that of ICG/PLGA formulation. The therapeutic effect (mean survival) was
      evaluated in a C6 rat glioma model. Surgical tumor resection alone showed almost
      no effect on survival (controls, 18 d; surgical resection; 18.5 d). Survival was
      prolonged after the treatment with a camptothecin (CPT; 10 ug)/PLGA/TGP
      formulation (24 d). The combination treatment of surgical tumor resection and
      CPT/PLGA/TGP showed almost the same therapeutic effect (24 d) compared with
      CPT/PLGA/TGP alone, while the combination treatment produced long term survivors
      (>60 d). Therefore, the CPT/PLGA/TGP formulation can be an effective candidate
      for localized and sustained long-term glioma therapy.

PMID- 22466558
TI  - Gallotannin suppresses calcium oxalate crystal binding and oxalate-induced
      oxidative stress in renal epithelial cells.
AB  - Calcium oxalate monohydrate (COM) crystals bind avidly to the surface of
      proliferating and migrating renal endothelial cells, perhaps a key event in
      kidney stone formation. Oxalate-induced pre-oxidative stress can further promote
      crystal attachment cells. Natural products including gallotannins found in green
      teas have been studied as potentially novel treatments to prevent crystal
      retention and kidney stone formation. Gallotannin significantly inhibited COM
      crystal growth and binding to Madin-Darby Canine Kidney Cells type I (MDCK I)
      renal epithelial cells at non-toxic concentrations. Reverse transcription
      polymerase chain reaction (RT-PCR) analysis revealed that gallotannin
      significantly attenuated oxalate-induced mRNA and protein expressions of monocyte
      chemoattractant protein 1 (MCP-1), osteopontin (OPN), nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase subunit p22(phox) and p47(phox) in human
      primary renal epithelial cells (HRCs). Gallotannin also reduced the levels of
      reactive oxygen species (ROS) and malondialdehyde (MDA) as well as enhanced
      antioxidant enzyme superoxide dismutase (SOD) activity in oxalate treated HRCs.
      Taken together, our findings suggest that gallotannin can contribute to
      nephrolithiasis prevention via direct effects on renal epithelial cells including
      suppression of COM binding and MCP-1 and OPN expression, along with augmenting
      antioxidant activity.

PMID- 22466560
TI  - Clearance of CD43-capped cells by macrophages: capping alone leads to
      phagocytosis.
AB  - Apoptotic cells must be recognized early for phagocytosis to ensure that their
      toxic contents do not damage neighboring cells. In some cases this is achieved
      via CD43-capped membrane glycoproteins, the sialylpolylactosaminyl chains of
      which serve as ligands for phagocytosis by macrophages. However, because many
      additional changes occur during apoptosis, determining exactly which events are
      responsible for signaling macrophages to initiate phagocytosis remains a
      challenge. Here, we examined one clearance mechanism in detail and determined
      that capping of CD43 alone is sufficient to initiate phagocytosis. We induced
      macrophage-mediated phagocytosis by using cytochalasin B to artificially cap CD43
      on healthy (non-apoptotic) Jurkat cells. Additional experiments confirmed that
      sialylpolylactosaminyl chains formed through this capping method are a
      prerequisite for removal, and that nucleolin is the macrophage receptor
      responsible for their detection. These findings strongly suggest that capping of
      CD43 presents a sufficient signal for phagocytosis without any additional
      membrane changes.

PMID- 22466561
TI  - Preparative isolation and purification of neuroprotective compounds from Rhus
      verniciflua by high speed counter-current chromatography.
AB  - In the present study, extracts from Rhus verniciflua were demonstrated to
      significantly attenuate the negative effects of hydrogen peroxide (H(2)O(2)) on
      transformed retinal ganglion cell line (RGC-5 cells), indicating that they may be
      protective against oxidative stress-induced retinal degeneration. The inclusion
      of R. verniciflua in the culture was found to both reduce the levels of reactive
      oxygen species (ROS) present and lessen the up-regulation of apoptotic proteins
      such as cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved
      caspase-9. Active compounds were also successfully isolated from R. verniciflua
      using high-speed counter-current chromatography (HSCCC) with a two-phase solvent
      system composed of n-hexane-ethyl acetate-methanol-water (3.5:5:3.5:5, v/v).
      Using this method, we successfully separated 252.1 mg of fustin at a purity of
      over 93.09%, 51.2 mg of fisetin at a purity of over 95.45%, 39.7 mg of sulfuretin
      at a purity of over 95.17%, and 10.7 mg of butein at a purity of over 95.01% from
      1.5 g of R. verniciflua extract. The chemical structures of these compounds were
      elucidated by chemical and spectral analyses. There isolated compounds also
      significantly attenuated the negative effects of H(2)O(2) on RGC-5 cells. Results
      therefore suggest that, due to its anti-oxidative and anti-apoptotic effects, R.
      verniciflua could be used as a lead substance for the treatment of retinal
      diseases such as glaucoma.

PMID- 22466562
TI  - Beneficial effects by intake of Euphausiacea pacifica on high-fat diet-induced
      obesity.
AB  - Obesity is a major health problem showing increased incidence in developed and
      developing countries. We examined the effect of Euphausia pacifica (E. pacifica)
      (Pacific Krill) on high-fat diet (HFD)-induced obesity in C57BL/6 mice. No
      significant differences were observed in average food intake between the HFD and
      HFD with E. pacifica group, or the low-fat diet (LFD) and LFD with E. pacifica
      group for 18 weeks. The increased ratio of body weight in the HFD containing E.
      pacifica group was significantly reduced, being 10% lower than that with HFD
      group in the 18th week (HFD, 298.6+/-18.8% vs. HFD with E. pacifica, 267.8+/
      16.2%; p<0.05), while the ratio for the LFD containing E. pacifica group was
      reduced by 4% compared with LFD group (LFD, 244.2+/-11.6% vs. LFD with E.
      pacifica, 234.1+/-18.0%). There were no effects of E. pacifica on total
      cholesterol levels in serum and liver, whereas the supplement of E. pacifica
      tended to decrease triglyceride levels in the HFD groups. The leptin level in
      serum was significantly decreased in the HFD group (p<0.01) by E. pacifica. The
      adipocyte area (1926+/-1275 MUm(2)) in the HFD containing E. pacifica group was
      significantly reduced by 20% (p<0.001) compared with the HFD group. These results
      suggested that E. pacifica supplementation in the diet is beneficial for the
      prevention of HFD-induced obesity.

PMID- 22466563
TI  - Metabolism of ginsenoside Rb1 by human intestinal microflora and cloning of its
      metabolizing beta-D-glucosidase from Bifidobacterium longum H-1.
AB  - To understand the role of intestinal microflora in expressing the pharmacological
      effect of ginsenoside Rb1, the metabolic activity of ginsenoside Rb1 by 148 fecal
      specimens was measured and its metabolizing beta-glucosidase was cloned. The
      average activities for p-nitrophenyl-beta-D-glucopyranoside and ginsenoside Rb1
      were 0.097+/-0.059 MUmol/min/mg and 0.311+/-0.118 pmol/min/mg, respectively.
      These enzyme activities were not different between male and female, or between
      ages. A gene encoding beta-D-glucosidase (BglX) was cloned from Bifidobacterium
      longum H-1, which transformed ginsenoside Rb1 to compound K. The probe for
      cloning was synthesized from the genes encoding a beta-D-glucosidase of
      previously reported B. longum DJO10A. The sequences of the cloned gene revealed
      2364 bp open reading frame (ORF) encoding a protein containing 787 amino acids
      (molecular weight of 95 kDa). The gene exhibited 99% homology (identities) to
      that of B. longum. The cloned gene was expressed under T7 promoter of the
      expression vector, pET-39b(+), in Escherichia coli BL21(DE3), and the expressed
      enzyme was purified by using HiTrap immobilized metal affinity chromatography
      (IMAC) HP. The enzyme potently biotransformed ginsenoside Rb1, loganin, arctiin
      and arbutin to ginsenoside Rd, loganetin, arctigenin and hydroquinone,
      respectively, but was not active in the case of hesperidin, and kakkalide. This
      is the first report on cloning and expression of beta-D-glucosidase from B.
      longum. Based on these findings, ginsenoside Rb1 may be metabolized to bioactive
      compound(s) by exo-beta-D-glucosidase(s) produced from the intestinal bacteria
      and its pharmacological effects may be dependent on intestinal bacterial exo-beta
      D-glucosidase(s) activity.

PMID- 22466564
TI  - Hairless modulates ligand-dependent activation of the vitamin D receptor-retinoid
      X receptor heterodimer.
AB  - The active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)],
      binds to the vitamin D receptor (VDR) and regulates various physiological and
      pharmacological processes. Secondary bile acids, such as lithocholic acid (LCA),
      also act as endogenous VDR ligands. The molecular basis of ligand-selective VDR
      action remains largely unknown. Hairless (HR) acts as a coregulator of VDR
      through a direct interaction. HR mutations confer an alopecia phenotype similar
      to VDR mutations in mice and humans, but the underlying molecular mechanisms have
      not been elucidated. We examined the effect of HR on VDR activation induced by
      1,25(OH)(2)D(3) and LCA. HR repressed VDR transactivation induced by both
      1,25(OH)(2)D(3) and LCA. HR also repressed transactivation of VDR E269A and R391A
      mutants, but less effectively than that of wild-type VDR. These residues are
      involved in retinoid X receptor (RXR) heterodimer allosteric communication,
      through which information from ligands is transmitted to dimer and coactivator
      interfaces. In the presence of HR cotransfection, LCA activated these VDR mutants
      more effectively than wild-type VDR. In mammalian two-hybrid assays, HR enhanced
      the association of VDR with a corepressor, nuclear receptor corepressor. These
      findings indicate that HR affects VDR-RXR heterodimer allosteric communication
      and corepressor complex formation. Interestingly, HR knockdown in keratinocyte
      derived HaCaT cells increased ligand-induced cytochrome P450, family 24,
      subfamily A, polypeptide 1 (CYP24A1) expression but suppressed expression of
      cathelicidin antimicrobial peptide, indicating that HR acts not only as a
      corepressor but also as a coactivator. HR may be a VDR modulator that affects the
      RXR allosteric communication network in order to regulate transcription in a gene
      selective manner.

PMID- 22466566
TI  - Unlike natural killer (NK) p30, natural cytotoxicity receptor NKp44 binds to
      multimeric alpha2,3-NeuNAc-containing N-glycans.
AB  - Natural cytotoxicity receptor 2 (NCR2 or natural killer (NK)p44) and NCR3 (NKp30)
      bind to heparin and heparin sulfate; however, other natural ligands have yet to
      be identified. We previously reported that NCR1 (NKp46) can bind to multimeric
      NeuNAc-containing N-glycans and sulfated glycans. In this study, we investigated
      whether NKp44 and NKp30 can bind to NeuNAc-containing glycans using their common
      recombinant extracellular domain tagged with 6*His (NKp44-H6 and NKp30-H6). NKp44
      H6, but not NKp30-H6, bound multimeric sialyl Lewis X expressing transferrin
      secreted by HepG2 cells (HepTF) with a K(d) of 420 nM. Competitive and direct
      binding assays revealed that NKp44-H6 mainly recognizes alpha2,3-NeuNAc residues
      on non-reducing ends of N-glycans on HepTF. Moreover, site-directed mutants of
      NKp44-H6, such as R47Q, R55Q, R92Q, R95Q, K103Q, and R106Q, had reduced binding
      to alpha2,3-sialylated N-glycans. These results suggest that NKp44 binds to
      alpha2,3-sialylated N-glycans through ionic interactions, and that these binding
      sites might have some overlap with heparin binding sites.

PMID- 22466565
TI  - In vitro study on the transport of zinc across intestinal epithelial cells using
      Caco-2 monolayers and isolated rat intestinal membranes.
AB  - The variety of physiologic and biologic functions of zinc is fascinating and
      could be applicable to medicine. Our previous studies demonstrated that the
      absorption of zinc after oral administration to rats is dose-dependent. In order
      to clarify the detailed mechanism of the dose-dependent in vivo absorption, the
      transport of zinc across intestinal epithelial cells was investigated using Caco
      2 monolayers and isolated rat intestinal membranes. The permeation of zinc across
      Caco-2 monolayers is concentration-dependent, and both saturable and nonsaturable
      components are involved. The Michaelis constant and maximum transport rate for
      saturable transport are 11.7 MUM and 31.8 pmol min(-1) cm(-2), respectively; the
      permeability coefficient for nonsaturable trasnport is 2.37*10(-6) cm s(-1).
      These parameters for permeation across membranes isolated from duodenum, ileum,
      and jejunum of rats are similar with those of Caco-2 cells. The comparison of the
      parameters for permeation across isolated intestinal membrane suggests that the
      major site of intestinal zinc absorption in rats is the duodenum. The maximum
      rate of zinc transport across the isolated intestinal membrane (V(max)) shows no
      correlation with mRNA expression of ZIP4, ZIP5 or ZnT1 in rats, but shows an
      inverse correlation with that of metallothioneins (MTs). This finding may be
      partly explained by the buffering role of metallothionein in intestinal
      absorption. The saturable transport of zinc is not simply determined only by the
      influx transporter, ZIP4, since three influx and efflux transporters are involved
      in the transport of zinc.

PMID- 22466567
TI  - Exon 10 coding sequence is important for endoplasmic reticulum retention of
      endoplasmic reticulum aminopeptidase 1.
AB  - Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a final trimming enzyme of N
      extended antigenic peptides bound to major histocompatibility complex class I
      molecules in the endoplasmic reticulum (ER). In our previous work, we found that
      ERAP1 is secreted from macrophages in response to activation by
      lipopolysaccharide and interferon-gamma. In this paper, we searched for the amino
      acid sequence of ERAP1 protein important for ER retention by constructing
      chimeric proteins and found that the sequence between 485 and 615 was
      significant. Moreover, by comparing the genomic organizations of oxytocinase
      subfamily members, the exon 10 coding sequence, which might be inserted into the
      common ancestral gene of the oxytocinase subfamily enzymes during evolution, was
      found to be important for ER retention of ERAP1. Taken together, our data
      indicate that ERAP1 contains amino acid sequence important for ER retention.

PMID- 22466568
TI  - Phosphoenolpyruvic acid, an intermediary metabolite of glycolysis, as a potential
      cytoprotectant and anti-oxidant in HeLa cells.
AB  - This study examined the cytoprotective and anti-oxidative properties of
      phosphoenolpyruvic acid (PEP), a glycolysis metabolite with a high-energy
      phosphate group. PEP (0.1-10 mM) significantly attenuated the decrease in cell
      viability induced by hydrogen peroxide (H(2)O(2)) in HeLa cells in a dose
      dependent manner. PEP also inhibited the decrease in calcein-acetomethoxy-stained
      cells and the increase in propidium iodide-stained cells that were induced by
      H(2)O(2). The H(2)O(2)-stimulated increase in intracellular reactive oxygen
      species was significantly reduced by PEP. PEP also demonstrated scavenging
      potential against hydroxyl radicals, as assessed by the electron paramagnetic
      resonance method. In addition, PEP demonstrated scavenging potential against the
      1,1-diphenyl-2-picrylhydrazyl radical, a representative artificial radical,
      although the potential is very weak. PEP (10 mM) slightly inhibited the decrease
      in cellular ATP content induced by H(2)O(2), but did not show any effects at low
      doses (0.1, 1 mM). PEP (0.1-10 mM) also attenuated the cell injury but not the
      decrease in intracellular ATP content, induced by 2-deoxy-D-glucose, a glycolysis
      inhibitor. These results indicate that PEP exerts cytoprotective effects and has
      anti-oxidative potential, although the precise cytoprotective mechanisms are not
      fully elucidated. We suggest that PEP is a functional carbohydrate metabolite
      with cytoprotective and anti-oxidative activity, and is potentially useful as a
      therapeutic agent against diseases that involve the oxidative stress.

PMID- 22466569
TI  - Lactobacillus acidophilus strain L-92 induces CD4(+)CD25(+)Foxp3(+) regulatory T
      cells and suppresses allergic contact dermatitis.
AB  - The anti-allergic mechanism of heat-killed Lactobacillus acidophilus strain L-92
      has not been fully investigated. Recent studies have reported that
      CD4(+)CD25(+)Foxp3(+) (forkhead box P3) T regulatory (Treg) cells play important
      roles in controlling allergic diseases. Hence, we examined the effect of orally
      administered L-92 on CD4(+)CD25(+)Foxp3(+) cell populations. BALB/c mice were
      supplemented daily with L-92 by gavage for 5 weeks. 2,4-Dinitrofluorobenzene
      (DNFB) was used to induce allergic contact dermatitis (ACD) in mice. Fluorescent
      activated cell sorter (FACS) analysis was used to determine CD4(+)CD25(+)Foxp3(+)
      T cell populations in spleen and cervical lymph nodes (CLN). Interleukin-10 (IL
      10), transforming growth factor-beta (TGF-beta), and Foxp3 mRNA expressions in
      mouse ear skin were investigated by real-time reverse transcription-polymerase
      chain reaction (RT-PCR). The percentage of CD4(+)CD25(+)Foxp3(+) T cell
      populations were significantly increased in both spleen and CLN of L-92-fed group
      than vehicle and control. In addition, L-92 produced higher levels of Foxp3, IL
      10 and TGF-beta compared to control mice. These results suggest that L-92 can up
      regulate the number of Treg cells to suppress the progression of DNFB-induced
      contact dermatitis in mice.

PMID- 22466570
TI  - Vitamin K3 analogs induce selective tumor cytotoxicity in neuroblastoma.
AB  - We investigated the cytotoxicity of eight vitamin K3 (VK3) analogs against
      neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, and SK-N-SH) and normal cell
      lines (human umbilical vein endothelial cells (HUVEC) and human dermal
      fibroblasts (HDF)) using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide (MTT) assay. 2-[(2-Methoxy)ethylthio]-3-methyl-1,4-naphthoquinone (VK3
      OCH(3)) showed especially potent cytotoxic activities against neuroblastoma cells
      compared with normal cells. In a Hoechst 33342 staining experiment, apoptotic
      morphologies characterized by cell shrinkage, nuclear condensation, and nuclear
      fragmentation were observed in IMR-32 and LA-N-1 cells after 48 h of treatment
      with 10(-5) M of VK3-OCH(3). To clarify the molecular mechanisms of apoptosis
      induced by VK3-OCH(3), we examined the expression of apoptosis related proteins
      using a Proteome Profiler Array and western blotting. Heme oxygenase (HO)-1 was
      remarkably increased by VK3-OCH(3) compared with the control (173% in IMR-32 and
      170% in LA-N-1 at 24 h). Moreover, caveolin-1 was induced by VK3-OCH(3) at 48 h.
      In addition, VK3-OCH(3) arrested the cell cycle at the G2/M phase in IMR-32
      cells. These results suggest that VK3-OCH(3) exhibited a selective antitumor
      activity via HO-1-related mechanisms.

PMID- 22466571
TI  - The involvement of cleavage of neural cell adhesion molecule in neuronal death
      under oxidative stress conditions in cultured cortical neurons.
AB  - Neural cell adhesion molecule (NCAM) is a member of the immunoglobulin
      superfamily with an important function in the central nervous system,
      particularly in synapse stabilization and neurite outgrowth. Our recent study
      clearly demonstrated that cleavage of NCAM-180 by matrix metalloproteinase-9 (MMP
      9) exacerbated the neuronal damage induced by in vivo ischemic stress. In the
      present study, we investigated the effect of oxidative stress on the expression
      levels of full-length NCAM-180 and NCAM-cleavage product (65 kDa) and the
      relationship between NCAM-180 and MMP-9 in cultured cortical neurons. Primary
      cultured cortical neurons were exposed to oxidative stress by administration of
      hydrogen peroxide into the culture medium. After exposure to oxidative stress,
      cell death of cultured cortical neurons was gradually increased in a time
      dependent manner. In parallel to the cell death, levels of full-length NCAM-180
      and its cleavage product (65 kDa) were gradually and significantly decreased and
      increased, respectively, in a time-dependent manner. These changes completely
      disappeared following addition of an MMP-9 inhibitor, while MMP-9 protein levels
      were increased only in the early phase of oxidative stress. We conclude that
      oxidative stress can induce cleavage of NCAM-180 through up-regulation of MMP-9
      during the early phase of oxidative stress. These changes might be related to the
      neuronal death observed under oxidative stress conditions.

PMID- 22466572
TI  - Feasibility of structural modification of retinoid X receptor agonists to
      separate blood glucose-lowering action from adverse effects: studies in KKA(y)
      type 2 diabetes model mice.
AB  - Retinoid X receptor (RXR) agonists are reported to exhibit blood glucose-lowering
      action owing to peroxisome proliferator-activated receptor (PPAR)/RXR or liver X
      receptor (LXR)/RXR activation, but may also cause adverse effects such as blood
      triglyceride elevation. In order to examine the feasibility of separating the
      glucose-lowering action from the adverse effects, we examined the effects of RXR
      agonists (NEt-TMN), NEt-3IB, and NEt-3IP, which have different heterodimer
      activating patterns, in KKA(y) type 2 diabetes model mice. We found that NEt-3IB
      induced lower degrees of hepatomegaly and blood triglyceride (TG) elevation than
      the other RXR agonists, even though all of them showed similar blood glucose
      lowering action on repeated administration. These findings indicate that
      structural modification of RXR agonists is a potentially effective strategy to
      reduce adverse effects while retaining desired activities.

PMID- 22466573
TI  - Contribution of reductase activity to quinone toxicity in three kinds of hepatic
      cells.
AB  - Two mechanisms have been proposed to explain quinone cytotoxicity: oxidative
      stress via the redox cycle, and the arylation of intracellular nucleophiles. The
      redox cycle is catalyzed by intracellular reductases, and therefore the toxicity
      of redox cycling quinone is considered to be closely associated with the
      reductase activity. This study examined the relationship between quinone toxicity
      and the intracellular reductase activity using 3 kinds of hepatic cells; rat
      primary hepatocytes, HepG2 and H4IIE. The intracellular reductase activity was;
      primary hepatocyte >>HepG2>H4IIE. The three kinds of cells showed almost the same
      vulnerability to an arylating quinone, 1,4-naphthoquinone (NQ). However, the
      susceptibility to a redox cycling quinone, 2,3-dimethoxy-1,4-naphthoquinone
      (DMNQ) was; primary hepatocyte>HepG2>H4IIE. In addition, the cytotoxicity
      elicited by DMNQ was significantly attenuated in HepG2 cells and almost
      completely suppressed in primary hepatocytes by diphenyleneiodonium chloride, a
      reductase inhibitor. These data suggest that cells with a high reductase activity
      are susceptible to redox cycling quinones. This study provides essential evidence
      to assess the toxicity of quinone-based drugs during their developmental
      processes.

PMID- 22466574
TI  - Metabolomics study on the biochemical profiles of odor elements in urine of human
      with bladder cancer.
AB  - It has been reported that dogs are capable of identifying cancer in humans by
      detecting a specific odor: bladder cancer by detecting urine odor and other
      cancers by detecting exhaled breath odor. However, no odor recognized by dogs
      that indicates cancer has been identified. In this study, we examined whether
      bladder cancer could be detected by gas chromatography-mass spectrometry (GC-MS)
      based metabolomics analysis of urine odor. Nine patients with bladder cancer and
      7 healthy controls were recruited as participants. Patients collected urine 3 d
      before and for 3-7 d after surgery. The concentrated urine odor was analyzed by
      GC-MS and principal component analysis (PCA). Results indicated 12 metabolites of
      urine odor. Score plots of 7 of the preoperative bladder cancer patients were
      clearly different from those of controls on the PCA map. The distribution of
      controls was in the negative domain of principal component (PC) 1, whereas the
      distribution of preoperative patients was in the positive domain of PC1. Bladder
      cancer was diagnosed in 5 of the 9 patients on the basis of urinary cytology. The
      findings indicate the potential to screen bladder cancer by analyzing urine odor.
      Moreover, diagnosis of bladder cancer on the basis of urine odor might have
      higher sensitivity than screening by urinary cytology.

PMID- 22466575
TI  - Are "patterns" of lumbar disc degeneration associated with low back pain?: new
      insights based on skipped level disc pathology.
AB  - STUDY DESIGN: A cross-sectional, population-based cohort study. OBJECTIVE: The
      objective of this study was to evaluate the clinical relevance of skipped level
      disc degeneration (SLDD) to that of contiguous, multilevel disc degeneration
      (CMDD) of the lumbar spine. The study also aimed to identify patterns of SLDD,
      its classification, prevalence, and clinical relevance. SUMMARY OF BACKGROUND
      DATA: The association of disc degeneration on magnetic resonance imaging with low
      back pain (LBP) remains questionable. The occurrence of SLDD of the lumbar spine
      has recently been noted. To date, patterns of disc degeneration have been
      overlooked in the association with low back symptoms. METHODS: A population-based
      radiographic and clinical study of 3099 Southern Chinese patients. Individuals
      with multilevel disc degeneration of the lumbar spine on sagittal T2-weighted
      magnetic resonance imaging (N = 1457) were stratified to SLDD (n = 301; 20.7%) or
      CMDD (n = 1156; 79.3%) groups. SLDD was further classified into 5 types by the
      relative location of nondegenerated normal disc(s) to degenerated disc levels.
      Subject demographics, presence of LBP, pain intensity, and functional disability
      were assessed. RESULTS: In the multivariate analyses, CMDD increased the
      likelihood of historical LBP (odds ratio [OR]: 1.39; 95% confidence interval
      [CI]: 1.00-1.93; P = 0.047) and pain severity (OR: 1.83; 95% CI: 1.23-2.73; P =
      0.003) in comparison with SLDD. A significant increasing trend of number of
      levels with disc degeneration, overall disc degeneration severity, and presence
      of disc bulges/extrusions was noted from SLDD type I (least severe) to SLDD type
      V (most severe) (P < 0.05). A higher prevalence of LBP and a higher pain
      intensity were observed in SLDD classification type V. Functional disability
      scores did not differ between CMDD and SLDD, nor within SLDD classification types
      (P > 0.05). CONCLUSION: Our large-scale study is the first to describe novel
      variants of SLDD types and their clinical relevance. More important, LBP and
      severity of pain were more pronounced in individuals with CMDD rather than those
      with SLDD. Our study suggests that subjects with a similar degree but different
      patterns of multilevel disc degeneration do differ with respect to low back
      symptoms. This finding may provide new evidence with regard to the mechanism of
      LBP.

PMID- 22466576
TI  - MAX2 affects multiple hormones to promote photomorphogenesis.
AB  - Ubiquitin-26S proteasome system (UPS) has been shown to play central roles in
      light and hormone-regulated plant growth and development. Previously, we have
      shown that MAX2, an F-box protein, positively regulates facets of
      photomorphogenic development in response to light. However, how MAX2 controls
      these responses is still unknown. Here, we show that MAX2 oppositely regulates GA
      and ABA biosynthesis to optimize seed germination in response to light. Dose
      response curves showed that max2 seeds are hyposensitive to GA and hypersensitive
      to ABA in seed germination responses. RT-PCR assays demonstrated that the
      expression of GA biosynthetic genes is down-regulated, while the expression of GA
      catabolic genes is up-regulated in the max2 seeds compared to wild-type.
      Interestingly, expression of both ABA biosynthetic and catabolic genes is up
      regulated in the max2 seeds compared to wild-type. Treatment with an auxin
      transport inhibitor, NPA, showed that increased auxin transport in max2 seedlings
      contributes to the long hypocotyl phenotype under light. Moreover, light
      signaling phenotypes are restricted to max2, as the biosynthetic mutants in the
      strigolactone pathway, max1, max3, and max4, did not display any defects in seed
      germination and seedling de-etiolation compared to wild-type. Taken together,
      these data suggest that MAX2 modulates multiple hormone pathways to affect
      photomorphogenesis.

PMID- 22466577
TI  - A longitudinal analysis of the impact of hospital service line profitability on
      the likelihood of readmission.
AB  - Quality of care may be linked to the profitability of admissions in addition to
      level of reimbursement. Prior policy reforms reduced payments that differentially
      affected the average profitability of various admission types. The authors
      estimated a Cox competing risks model, controlling for the simultaneous risk of
      mortality post discharge, to determine whether the average profitability of
      hospital service lines to which a patient was admitted was associated with the
      likelihood of readmission within 30 days. The sample included 12,705,933 Medicare
      Fee for Service discharges from 2,438 general acute care hospitals during 1997,
      2001, and 2005. There was no evidence of an association between changes in
      average service line profitability and changes in readmission risk, even when
      controlling for risk of mortality. These findings are reassuring in that the
      profitability of patients' admissions did not affect readmission rates, and
      together with other evidence may suggest that readmissions are not an unambiguous
      quality indicator for in-hospital care.

PMID- 22466578
TI  - Equilibrium, kinetic and thermodynamic studies of mercury adsorption on almond
      shell.
AB  - The application of almond shell as a low cost natural adsorbent to remove Hg(2+)
      from aqueous solution was investigated. Batch experiments were carried out to
      evaluate the adsorption capacity of the material. The chemical and physical
      parameters such as pH, sorbent amount, initial ion concentration, and contact
      time were optimized for the maximum uptake of mercury onto the solid surface.
      Adsorption isotherms were expressed by Langmuir and Freundlich adsorption models,
      and the experimental data were found to fit the Langmuir model rather than the
      Freundlich. The maximum adsorption capacity obtained from the Langmuir isotherm
      was 135.13 mg/g. A kinetic study was carried out with pseudo-first-order and
      pseudo-second-order reaction equations and it was found that the Hg(2+) uptake
      process followed the pseudo-second-order rate expression. The thermodynamic
      values, DeltaG(0), DeltaH(0) and DeltaS(0), indicated that adsorption was an
      endothermic and spontaneous process. The potential of this material for mercury
      elimination was demonstrated by efficient Hg(2+) removal from a synthetic
      effluent.

PMID- 22466579
TI  - Use of human urine in phytoplankton production as a tool for ecological
      sanitation.
AB  - Measurements of primary productivity of phytoplankton and enumeration of the
      counts of coliform and heterotrophic bacteria (HB) were made in the water of 12
      experimental tanks used for 3 treatments and control in triplicate as follows:
      (a) fresh human urine (0.02%), (b) stored human urine (0.02%), (c) mixed urine of
      fresh and stored human urine (0.02%) and (d) control without input of urine. The
      gross primary productivity of phytoplankton was highest in the stored urine
      treated tanks (508 mg C m(-2) h(-1)) followed by fresh urine (353 mg C m(-2) h(
      1)), mixed urine (303 mg C m(-2) h(-1)) and control (215 mg C m(-2) h(-1)).
      Similar was the response of net primary production of phytoplankton. The mean
      count of HB observed in stored urine fed tanks was significantly higher (59-184%)
      than the remaining urine fed treatments. The mean count of Escherichia coli did
      not differ from urine treated tanks to control implying the good quality of
      water. The concentration of dissolved oxygen of water (7.6 to 12.8 mg L(-1)) in
      these tanks remained satisfactory for aquaculture. The mean concentration of
      ammonium-N observed in fresh urine treated tanks was more than 10 times higher
      than the remaining treatments employed. In contrast, the level of phosphate and
      electrical conductivity in the stored urine treated tanks were significantly
      higher than the remaining treatments. It is proposed that stored urine with a
      significantly reduced load of E. coli might be an effective low cost liquid
      fertilizer for algal biomass production.

PMID- 22466580
TI  - Parasitological risk assessment from wastewater reuse for disposal in soil in
      developing countries.
AB  - The purpose of this work is to analyze the parasitological risks of treated
      wastewater reuse from a stabilization pond in the city of Piracicaba, in the
      State of Sao Paulo (Brazil), and the level of treatment required to protect
      public health. Samples were taken from raw and treated wastewater in
      stabilization ponds and submitted to a parasitological, microbiological and
      physicochemical analysis. The study revealed on treated wastewater the presence
      of Ascaris sp. and Entamoeba coli with an average density of 1 cysts L(-1) and 6
      eggs L(-1), respectively. For Ascaris, the annual risks of infection due to the
      accidental ingestion of wastewater irrigation were 7.5 * 10(-2) in 208 days and
      8.7 * 10(-2) in 240 days. For Total Coliforms and Escherichia coli in treated
      wastewater, the average density was 1.0 * 10(5) MPN/100 ml and 2.7 * 10(4)
      MPN/100 ml respectively, representing 99% and 94% removal efficiency,
      respectively. For BOD, COD, TS and TSS removal efficiency was 69, 80, 50 and 71%,
      respectively. The removal efficiency for nitrogen; ammonia nitrogen and total
      phosphate was 24, 19 and 68%, respectively. The average density of helminths eggs
      in treated wastewater is higher compared to the density of the limit value of <=1
      egg L(-1) and tolerable risk is above the level recommended by the World Health
      Organization. Multiple barriers are necessary for the reduction of organic
      matter, chemical contaminants and parasites from treated wastewater. Standards
      for the sanitary control of treated wastewater to be reused in agricultural
      irrigation areas should be compiled for developing countries in order to minimize
      public health risks.

PMID- 22466581
TI  - Robustness of the microaerobic removal of hydrogen sulfide from biogas.
AB  - Several disturbances presented in full-scale digesters can potentially affect the
      efficiency of the microaerobic removal process. This study evaluates the
      variation of the sulfur load and the performance of the system in situations of
      oxygen lack or excess and after normal rates are recovered. The process was shown
      to recover from oxygen lack or excess within 28 h when the original conditions
      were restored in a pilot-plant digester of 200 L treating sewage sludge with HRT
      of 20 days. The decrease of the sulfur load to the digester did not affect the
      biogas composition in the short-term and when oxygen rate was reduced to adjust
      to the lower hydrogen sulfide production, the removal proceeded normally with a
      lower unemployed oxygen amount. The digester opening to remove accumulated sulfur
      in the headspace did not alter process performance once the microaerobic removal
      was restarted.

PMID- 22466582
TI  - Influence of dye type and salinity on aerobic decolorization of azo dyes by
      microbial consortium and the community dynamics.
AB  - In this research, aerobic decolorization of different azo dyes by a microbial
      community was studied. The results showed that more than 80% of four azo dyes
      (100 mg/L) could be aerobically decolorized by the microbial consortium, however,
      the time needed was obviously different. Kinetic data indicated that the
      processes were well described by zero-order kinetics, and the chemical structures
      of dyes had obvious influence on decolorization rates. On the other hand, effects
      of salinity on decolorization were also investigated. There was still 40% dye
      removal for Acid Brilliant Red GR when the salinity increased to 250 g/L. And the
      microbial community structures with different salinity were detected by PCR-DGGE.
      It was shown that the same two bacteria were dominant in all decolorization
      systems, and some typical halophilic microorganisms were found under higher-salt
      conditions.

PMID- 22466583
TI  - Poly(acrylic acid) modifying bentonite with in-situ polymerization for removing
      lead ions.
AB  - In this paper, a new kind of poly(acrylic acid) modified clay adsorbent, the
      poly(acrylic acid)/bentonite composite (PAA/HB) was prepared by in-situ
      polymerization, and utilized to remove lead(II) ions from solutions. The maximum
      adsorption of adsorbent is at pH 5 for metal ions, whereas the adsorption starts
      at pH 2. The effects of contact time (5-60 min), initial concentration of metal
      ions (200-1,000 mg/L) and adsorbent dosage (0.04-0.12 g/100 mL) have been
      reported in this article. The experimental data were investigated by means of
      kinetic and equilibrium adsorption isotherms. The kinetic data were analyzed by
      the pseudo-first-order and pseudo-second-order equation. The experimental data
      fitted the pseudo-second-order kinetic model very well. Langmuir and Freundlich
      isotherms were tried for the system to better understand the adsorption isotherm
      process. The maximal adsorption capacity of the lead(II) ions on the PAA/HB, as
      calculated from the Langmuir model, was 769.2 mg/g. The results in this study
      indicated that PAA/HB was an attractive candidate for removing lead(II) (99%).

PMID- 22466584
TI  - Optimised photocatalytic degradation of a mixture of azo dyes using a
      TiO(2)/H(2)O(2)/UV process.
AB  - The aim of the present study was to optimise the photocatalytic degradation of a
      mixture of six commercial azo dyes, by exposure to UV radiation in an aqueous
      solution containing TiO(2)-P25. Response surface methodology, based on a 3(2)
      full factorial experimental design with three replicates was employed for process
      optimisation with respect to two parameters: TiO(2) (0.1-0.9 g/L) and H(2)O(2) (1
      100 mmol/L). The optimum conditions for photocatalytic degradation were achieved
      at concentrations of 0.5 g TiO(2)/L and 50 mmol H(2)O(2)/L, respectively. Dye
      mineralisation was confirmed by monitoring TOC, conductivity, sulfate and nitrate
      ions, with a sulfate ion yield of 96% under optimal reactor conditions. Complete
      decolorisation was attained after 240 min irradiation time for all tested azo
      dyes, in a process which followed a pseudo-first kinetic order model, with a
      kinetic rate constant of approximately 0.018 min(-1). Based on these results,
      this photocatalytic process has promise as an alternative for the treatment of
      textile effluents.

PMID- 22466585
TI  - Integrated modelling of sewer system and wastewater treatment plant for
      investigating the impacts of chemical dosing in sewers.
AB  - Chemicals are often dosed to control the production and accumulation of hydrogen
      sulfide in sewers. The biological and/or chemical actions of these chemicals have
      profound impacts on the composition of wastewater entering a WWTP, thereby
      affecting its performance. In this paper, an integrated modelling methodology for
      simultaneously investigating the effects of dosing of chemicals in sewer network
      and N and P removal at the downstream WWTP is reported. The sewer system is
      modelled using a sewer model (SeweX), and the WWTP is modelled using ASM2d model
      with some modifications. The importance of integrated modelling in sewer
      management is also demonstrated.

PMID- 22466586
TI  - The use of a rotating cylinder electrode to recover zinc from rinse water
      generated by the electroplating industry.
AB  - This work concerns the application of a laboratory scale rotating cylinder
      electrode (RCE) to recover zinc from rinse water generated by the electrolytic
      zinc process (initially 1,300, 4,400, 50, 20 mg L(-1) of Zn(II), Fe(III), Ag(I)
      and Cr(VI), respectively, at pH 2), although it is also applicable to other
      electroplating industries. Experimental results demonstrated the convenience of
      the removal of ferric ions, as (Fe(OH)(3(s))) by a pH adjustment to 4, before
      zinc electro recovery on the RCE. The generation of smooth zinc deposits on the
      RCE was obtained at Reynolds numbers within the range of 15,000 <= Re <= 124,000
      and limiting current densities (J(L)) in the interval of -4.8 to -13 mA cm(-2).
      The zinc recovery reached a conversion of 67% in 90 min of electrolysis for Re =
      124,000 and J = -13 mA cm(-2), 21% current efficiency, and energy consumption of
      9.5 kWh m(-3). The treated solution can be recycled back through the same rinsing
      process.

PMID- 22466587
TI  - Advanced phosphorus removal for secondary effluent using a natural treatment
      system.
AB  - Mechanisms for low concentrations phosphorus removal in secondary effluent were
      studied, and a process was developed using limestone filters (LF), submerged
      macrophyte oxidation ponds (SMOPs) and a subsurface vertical flow wetland (SVFW).
      Pilot scale experimental models were applied in series to investigate the
      advanced purification of total phosphorus (TP) in secondary effluent at the
      Chengjiang sewage treatment plant. With a total hydraulic residence time (HRT) of
      82.52 h, the average effluent TP dropped to 0.17 mg L(-1), meeting the standard
      for Class III surface waters. The major functions of the LF were adsorption and
      forced precipitation, with a particulate phosphorus (PP) removal of 82.93% and a
      total dissolved phosphorus (TDP) removal of 41.07%. Oxygen-releasing submerged
      macrophytes in the SMOPs resulted in maximum dissolved oxygen (DO) and pH values
      of 11.55 mg L(-1) and 8.10, respectively. This regime provided suitable
      conditions for chemical precipitation of TDP, which was reduced by a further
      39.29%. In the SVFW, TDP was further reduced, and the TP removal in the final
      effluent reached 85.08%.

PMID- 22466588
TI  - Characteristics of denitrifying granular sludge grown on nitrite medium in an
      upflow sludge blanket (USB) reactor.
AB  - While inoculating pre-acclimatized floccular sludge, nitrite-denitrifying
      granular sludge was obtained after approximately 40 days of cultivation in a 10 L
      upflow sludge blanket (USB) reactor. The nitrite removal efficiency was
      approximately 95% when the nitrite concentration was 50 mg L(-1)at an influent
      flow rate of 20 L h(-1). The nitrite granular sludge had several notable features
      including good settleability (110 m h(-1)), high ash content (79%), and high
      density (1.248 g cm(-3)). The mixed liquor suspended solids (MLSS) of the sludge
      bed remained at 130.04 g L(-1), at a hydraulic upflow velocity of 2 m h(-1).
      These interesting characteristics were attributed to a high effluent pH (9.7)
      caused by the release of alkalinity during the nitrite denitrification process.
      The surfaces of the granules were dominated by cocci bacteria with a diameter of
      approximately 3 MUm, which could be classified as Nitrosomonas-like species based
      on our analysis of 16 S rDNA sequences.

PMID- 22466589
TI  - The possibility of using encapsulated nitrifiers for treatment of reject water
      coming from anaerobic digestion.
AB  - Large wastewater treatment plants have to deal not only with the influent
      wastewater, but also with the highly concentrated reject water coming from
      anaerobic digestion. The aim of this work was to verify the suitability of using
      encapsulated nitrifiers in polyvinyl alcohol carrier (so called Lentikats
      Biocatalyst) at temperatures between 5 and 30  degrees C. For laboratory
      nitrification batch tests synthetic wastewater with ammonia nitrogen (Namon)
      concentration 10-800 mg L(-1) was used. The system has been proved to operate at
      the temperature of 10  degrees C, but not at 5  degrees C. It was found that the
      highest specific nitrification rates were observed at 30  degrees C and with
      ammonia nitrogen concentrations above 250 mg L(-1), which means that separate
      treatment of reject water by using encapsulated biomass seems to be an effective
      tool for wastewater treatment plant optimization.

PMID- 22466590
TI  - Removal of Ni(II) from aqueous solution using Moringa oleifera seeds as a
      bioadsorbent.
AB  - Metal contaminants are generally removed from effluents by chemical and physical
      processes which are often associated with disadvantages such as the use of toxic
      reagents, generation of toxic waste and high costs. Hence, new techniques have
      been developed, among them the study of natural adsorbents, for instance, the use
      of Moringa oleifera seeds. The potential of M. oleifera seeds for nickel removal
      in aqueous systems was investigated. The seeds utilized were obtained from plants
      grown in Uberlandia/Brazil. After being dried and pulverized, the seeds were
      treated with 0.1 mol/L NaOH. Fourier transform infrared spectroscopy, scanning
      electron microscopy and thermogravimetric analyses were used for the
      characterization of the material. Using the optimized methodology (50 mL of 4.0
      mg/L Ni(II), pH range of 4.0-6.0, agitation time of 5 min and adsorption mass of
      2.0 g) more than 90% of Ni(II) could be removed from water samples. The sorption
      data were fitted satisfactorily by the Langmuir adsorption model. Evaluation
      applying the Langmuir equation gave the monolayer sorption capacity as 29.6 mg/g.
      The results indicate that this material could be employed in the extraction of
      nickel, considering its ease of use, low cost and environmental viability, which
      make it highly attractive for application in developing countries.

PMID- 22466591
TI  - Determination of dairy wastewater treatability by bio-trickling filter packed
      with lava rocks - case study PEGAH dairy factory.
AB  - This paper investigates the effectiveness of a biological trickling filter for
      the treatment of wastewaters produced by a company manufacturing dairy products.
      First a bio-trickling column with a height of 150 cm was packed with lava rocks
      from north mountain of Tehran. It operates with the recirculation of liquid
      through the packing. In order to startup the pilot scale, steady state condition
      was gained by pumping activated sludge and dairy wastewater for 23 days.
      Afterwards, dairy wastewater was added to liquid tank for treatment. Hydraulic
      retention time (HRT) of treatment decreases from 5 days to 1 day then at HRT of
      12, 8, 7, 6 and 4 h. Results show that the average chemical oxygen demand (COD)
      decreased from 2,750 to 98 mg/L at HRT of 7 h and efficiency of TKN removal was
      more than 70%. The microorganisms developed in the bio-trickling filter were able
      to efficiently remove COD levels up to 2,750 mg/L, under aerobic conditions at pH
      values between 6.8 and 7.2 under low temperature condition between 10 and 13 
      degrees C.

PMID- 22466592
TI  - Pre-treating algae-laden raw water by silver carp during Microcystis-dominated
      and non-Microcystis-dominated periods.
AB  - Performance of pre-treating algae-laden raw water by silver carp during a non
      Microcystis-dominated period (period I) and a Microcystis-dominated period
      (period II) was investigated in terms of algae cell concentration, total
      phosphorus content, chlorophyll a and phytoplankton species structure. During
      period I the ineffective filter-feeding for small green algae resulted in the
      increase of small single algae, which led to the negative removal of chlorophyll
      a, and when the biomass was higher, the negative was more significant. However,
      due to the effective filter-feeding of silver carp for Microcystis flos-aquae,
      the average removal efficiency exceeded 50% at all stocking biomass levels (20
      120 g/m(3)) used in experiments during period II. Total phosphorus removal
      efficiencies could exceed 50% at silver carp biomass stocking levels of 60-80
      g/m(3) during both period I and period II. The experimental results indicated
      that silver carp stocking contributed to the removal of colony-forming
      cyanobacteria, but led to the increase of single-cell algae (mainly green algae
      and diatoms) during both period I and period II. The initial phytoplankton
      community structure and the control of nutrient level were important factors in
      the choice of silver carp stocking biomass when used to purify algae-loaded
      water.

PMID- 22466593
TI  - Long-term variations of water quality in a reservoir in China.
AB  - To study the spatial and temporal trends of water quality in the Yuqiao Reservoir
      (Ji County, Tianjin) in China, water quality data for ten physical and chemical
      parameters from three monitoring stations (S1, S2 and S3) was collected from 1989
      to 2007 and from an other three stations (S4, S5 and S6) during the period of
      1999-2007. A one-way ANOVA was employed to evaluate the spatial variation of
      water quality for each station. The results showed that there were statistically
      significant spatial differences for most water quality parameters except
      temperature and dissolved oxygen in the entire reservoir, and the concentrations
      of most parameters were higher in the uppermost part of the reservoir. The
      temporal trend study was conducted using the Seasonal-Kendall's test. The results
      revealed improving trends of water quality from 1989 to 2007, including a
      reduction of total phosphorous, temperature and biochemical oxygen demand and an
      increase of dissolved oxygen. High N:P ratios, ranging from 52.61 to 78.75,
      indicated that the reservoir was a phosphorous-limited environment. This study
      suggests long-term spatial and temporal variations of water quality in the Yuqiao
      Reservoir, which could be informative for water quality managers and scientists.

PMID- 22466594
TI  - Nutrient reference concentrations and trophic state boundaries in subtropical
      reservoirs.
AB  - Nutrient criteria as reference concentrations and trophic state boundaries are
      necessary for water management worldwide because anthropogenic eutrophication is
      a threat to the water uses. We compiled data on total phosphorus (TP), nitrogen
      (TN) and chlorophyll a (Chl a) from 17 subtropical reservoirs monitored from 2005
      2009 in the Sao Paulo State (Brazil) to calculate reference concentrations
      through the trisection method (United States Environmental Protection Agency). By
      dividing our dataset into thirds we presented trophic state boundaries and
      frequency curves for the nutrient levels in water bodies with different
      enrichment conditions. TP and TN baseline concentrations (0.010 mg/L and 0.350
      mg/L, respectively) were bracketed by ranges for temperate reservoirs available
      in the literature. We propose trophic state boundaries (upper limits for the
      oligotrophic category: 0.010 mg TP/L, 0.460 mg TN/L and 1.7 MUg Chl a/L; for the
      mesotrophic: 0.030 mg TP/L, 0.820 mg TN/L and 9.0 MUg Chl a/L). Through an
      example with a different dataset (from the Itupararanga Reservoir, Brazil), we
      encouraged the use of frequency curves to compare data from individual monitoring
      efforts with the expected concentrations in oligotrophic, mesotrophic and
      eutrophic regional systems. Such analysis might help designing recovery programs
      to reach targeted concentrations and mitigate the undesirable eutrophication
      symptoms in subtropical freshwaters.

PMID- 22466595
TI  - Electrocoagulative treatment of mercury containing aqueous solutions.
AB  - In recent years, electrocoagulation has been successfully used for wastewater
      treatment and is efficient in heavy metal ions removal. In the present work,
      electrocoagulation has been used for the removal of Hg(II) from synthetic
      wastewaters containing up to 20 mg/L of mercury. The electrode materials used are
      stainless steel (SS) and aluminum (Al). The effects of operating parameters,
      viz., current density, time of electrocoagulation, distance between electrodes,
      initial pH of the solution, presence of electrolyte in the solution and
      temperature have been studied. It was observed that more than 99% Hg(II) removal
      can be achieved by keeping the distance between SS and Al electrodes from 2 to 6
      cm and initial pH range from 3 to 7. The results show that the pseudo second
      order kinetics fits the data well. Also, preliminary cost estimation was
      reported.

PMID- 22466596
TI  - Implications to stormwater management as a result of lot scale rainwater tank
      systems: a case study in Western Sydney, Australia.
AB  - Rainwater tanks are increasingly adopted in Australia to reduce potable water
      demand and are perceived to reduce the volume of stormwater discharge from
      developments. This paper investigates the water balance of rainwater tanks, in
      particular the possible impacts these tanks could have in controlling the
      stormwater discharge volume. The study collected water quantity data from two
      sites in the Hawkesbury City Council area, New South Wales, Australia and
      utilised the collected data in a simple water balance model to assess the
      effectiveness of rainwater tanks in reducing the stormwater discharge volume. The
      results indicate that a significant reduction in discharge volume from a lot
      scale development can be achieved if the rainwater tank is connected to multiple
      end-uses, but is minimal when using irrigation alone. In addition, the commonly
      used volumetric runoff coefficient of 0.9 was found to over-estimate the runoff
      from the roof areas and to thereby under-estimate the available volume within the
      rainwater tanks for retention or detention. Also, sole reliance on the water in
      the rainwater tanks can make the users aware of their water use pattern and water
      availability, resulting in significant reductions in water use as the supply
      dwindles, through self-imposed water restrictions.

PMID- 22466597
TI  - Protein analysis as a measure of active biomass in activated sludge.
AB  - Conventional methods to determine the biomass in activated sludge are the
      measurement of total suspended solids (TSS) and volatile suspended solids (VSS).
      Such methods do not distinguish between active biomass and inactive organic
      material. In this study, biomass was determined with both conventional methods
      and also through measuring the protein content with the modified Lowry method. In
      order to investigate the relationship between activity and biomass concentration
      in terms of TSS, VSS and protein content, some starvation experiments were
      conducted. It was found that the protein fraction of VSS differs under different
      starvation conditions. The biological activity of the activated sludge was
      measured as oxygen uptake rate (OUR). The strongest correlation could be measured
      between protein and OUR under various conditions. The results show that protein
      is an appropriate parameter for the measurement of the biological activity.

PMID- 22466598
TI  - Bioremediation of direct dyes in simulated textile effluents by a paramorphogenic
      form of Aspergillus oryzae.
AB  - Azo dyes are extensively used for coloring textiles, paper, food, leather,
      drinks, pharmaceutical products, cosmetics and inks. The textile industry
      consumes the largest amount of azo dyes, and it is estimated that approximately
      10-15% of dyes used for coloring textiles may be lost in waste streams. Almost
      all azo dyes are synthetic and resist biodegradation, however, they can readily
      be reduced by a number of chemical and biological reducing systems. Biological
      treatment has advantages over physical and chemical methods due to lower costs
      and minimal environmental effect. This research focuses on the utilization of
      Aspergillus oryzae to remove some types of azo dyes from aqueous solutions. The
      fungus, physically induced in its paramorphogenic form (called 'pellets'), was
      used in the dye biosorption studies with both non-autoclaved and autoclaved
      hyphae, at different pH values. The goals were the removal of dyes by biosorption
      and the decrease of their toxicity. The dyes used were Direct Red 23 and Direct
      Violet 51. Their spectral stability (325-700 nm) was analyzed at different pH
      values (2.50, 4.50 and 6.50). The best biosorptive pH value and the toxicity
      limit, (which is given by the lethal concentration (LC(100)), were then
      determined. Each dye showed the same spectrum at different pH values. The best
      biosorptive pH was 2.50, for both non- autoclaved and autoclaved hyphae of A.
      oryzae. The toxicity level of the dyes was determined using the Trimmed Spearman
      Karber Method, with Daphnia similis in all bioassays. The Direct Violet 51
      (LC(100) 400 mg . mL(-1)) was found to be the most toxic dye, followed by the
      Direct Red 23 (LC(100) 900 mg . mL(-1)). The toxicity bioassays for each dye have
      shown that it is possible to decrease the toxicity level to zero by adding a
      small quantity of biomass from A. oryzae in its paramorphogenic form. The
      autoclaved biomass had a higher biosorptive capacity for the dye than the non
      autoclaved biomass. The results show that bioremediation occurs with A. oryzae in
      its paramorphogenic form, and it can be used as a biosorptive substrate for
      treatment of industrial waste water containing azo dyes.

PMID- 22466599
TI  - Benchmarking biological nutrient removal in wastewater treatment plants:
      influence of mathematical model assumptions.
AB  - This paper examines the effect of different model assumptions when describing
      biological nutrient removal (BNR) by the activated sludge models (ASM) 1, 2d & 3.
      The performance of a nitrogen removal (WWTP1) and a combined nitrogen and
      phosphorus removal (WWTP2) benchmark wastewater treatment plant was compared for
      a series of model assumptions. Three different model approaches describing BNR
      are considered. In the reference case, the original model implementations are
      used to simulate WWTP1 (ASM1 & 3) and WWTP2 (ASM2d). The second set of models
      includes a reactive settler, which extends the description of the non-reactive
      TSS sedimentation and transport in the reference case with the full set of ASM
      processes. Finally, the third set of models is based on including electron
      acceptor dependency of biomass decay rates for ASM1 (WWTP1) and ASM2d (WWTP2).
      The results show that incorporation of a reactive settler: (1) increases the
      hydrolysis of particulates; (2) increases the overall plant's denitrification
      efficiency by reducing the S(NOx) concentration at the bottom of the clarifier;
      (3) increases the oxidation of COD compounds; (4) increases X(OHO) and X(ANO)
      decay; and, finally, (5) increases the growth of X(PAO) and formation of
      X(PHA,Stor) for ASM2d, which has a major impact on the whole P removal system.
      Introduction of electron acceptor dependent decay leads to a substantial increase
      of the concentration of X(ANO), X(OHO) and X(PAO) in the bottom of the clarifier.
      The paper ends with a critical discussion of the influence of the different model
      assumptions, and emphasizes the need for a model user to understand the
      significant differences in simulation results that are obtained when applying
      different combinations of 'standard' models.

PMID- 22466600
TI  - Definition of realistic disturbances as a crucial step during the assessment of
      resilience of natural wastewater treatment systems.
AB  - Natural wastewater treatment systems (WWTSs) for urban areas in developing
      countries are subjected to large fluctuations in their inflow. This situation can
      result in a decreased treatment performance. The main aims of this paper are to
      introduce resilience as a performance indicator for natural WWTSs and to propose
      a methodology for the identification and generation of realistic disturbances of
      WWTSs. Firstly, a definition of resilience is formulated for natural WWTSs
      together with a short discussion of its most relevant properties. An important
      aspect during the evaluation process of resilience is the selection of
      appropriate disturbances. Disturbances of the WWTS are caused by fluctuations in
      water quantity and quality characteristics of the inflow. An approach to defining
      appropriate disturbances is presented by means of water quantity and quality data
      collected for the urban wastewater system of Coronel Oviedo (Paraguay). The main
      problem under consideration is the potential negative impact of stormwater inflow
      and infiltration in the sanitary sewer system on the treatment performance of
      anaerobic waste stabilisation ponds.

PMID- 22466601
TI  - Biosorption of heavy metals onto nonliving Laminaria japonica.
AB  - In this paper, study of the biosorption of Cd(2+) and Pb(2+) by nonliving
      Laminaria japonica in a batch adsorption system is described. The content of
      acidic sites and the dissociation constant of carboxylic acid functional groups
      (metal-binding site) of L. japonica were experimentally determined by
      conductometric and potentiometric titrations and theoretically predicated by
      using monodentate and bidentate binding models. The models are based on the
      monodentate or bidentate binding reactions of bivalent metal ions to acidic
      sites. The acidic site content and carboxylic acid dissociation constants
      determined are 1.25 and 0.18 mmol L(-1), respectively. The results showed that
      the bidentate adsorption model fits well the biosorption of bivalent metal ions
      onto L. japonica with the bidentate binding constants for Cd(2+) and Pb(2+) being
      5.72 * 10(3) and 6.24 * 10(4) L mol(-1), respectively. The adsorption process of
      L. japonica followed the pseudo-second-order kinetics.

PMID- 22466602
TI  - Nitrate estimation in the denitrifying post-filtration unit of a municipal
      wastewater treatment plant: the Viikinmaki case.
AB  - In this work we present and discuss the design of an array of soft-sensors to
      estimate the nitrate concentration in the denitrifying post-filtration unit at
      the Viikinmaki wastewater treatment plant in Helsinki (Finland). The developed
      sensors aim at supporting the existing hardware analyzers by providing a reliable
      back-up system in case of malfunction of the instruments. In the attempt to
      design easy to implement and interpretable sensors, computationally light linear
      models have been considered. However, due to the intrinsic nonlinearity of the
      process, also nonlinear but still computationally affordable models have been
      considered for comparison. The experimental results demonstrate the potential of
      the developed soft-sensors and the possibility for an on-line implementation in
      the plant's control system as alternative monitoring devices.

PMID- 22466603
TI  - All-trans-retinoid acid induces the differentiation of encapsulated mouse
      embryonic stem cells into GABAergic neurons.
AB  - Embryonic stem (ES) cells are pluripotent cells that can differentiate into all
      three main germ layers: endoderm, mesoderm, and ectoderm. Although a number of
      methods have been developed to differentiate ES cells into neuronal phenotypes
      such as sensory and motor neurons, the efficient generation of GABAergic
      interneurons from ES cells still presents an ongoing challenge. Because the main
      output of inhibitory GABAergic interneurons is the gamma-aminobutyric-acid
      (GABA), a neurotransmitter whose controlled homeostasis is required for normal
      brain function, the efficient generation in culture of functional interneurons
      may have future implications on the treatment of neurological disorders such as
      epilepsy, autism, and schizophrenia. The goal of this work was to examine the
      generation of GABAergic neurons from mouse ES cells by comparing an embryoid body
      based methodology versus a hydrogel-based encapsulation protocol that involves
      the use of all-trans-retinoid acid (RA). We observed that (1) there was a 2-fold
      increase in neuronal differentiation in encapsulated versus non-encapsulated
      cells and (2) there was an increase in the specificity for interneuronal
      differentiation in encapsulated cells, as assessed by mRNA expression and
      electrophysiology approaches. Furthermore, our results indicate that most of the
      neurons obtained from encapsulated mouse ES cells are GABA-positive (~87%). Thus,
      these results suggest that combining encapsulation of ES cells and RA treatment
      provide a more efficient and scalable differentiation strategy for the generation
      in culture of functional GABAergic interneurons. This technology may have
      implications for future cell replacement therapies and the treatment of CNS
      disorders.

PMID- 22466604
TI  - Insulin receptor isoforms are differently expressed during human
      osteoblastogenesis.
AB  - The reciprocal influence and bidirectional cross-talk between bone and energy
      metabolism is a recent finding, since the discovery that the product of
      osteoblasts osteocalcin increases pancreatic beta-cell proliferation, insulin
      secretion and sensitivity. Conversely, the anabolic effect of insulin is crucial
      for osteoblast function, as suggested by severe osteopenia and increased
      incidence of fracture in insulin-deficient diabetic patients. The Insulin
      Receptor (IR) tyrosine kinase, which is commonly expressed in the insulin
      sensitive liver, muscle, and adipose tissues, is also found in animal and human
      bone. Here we show that in human bone two insulin receptor isoforms (IR-A and IR
      B) are differently expressed. Mature human osteoblasts predominantly express IR
      B, whereas IR-A is mainly expressed in osteoblast precursors, and IR-B/IR-A mRNA
      ratio significantly increases along the osteogenic differentiation of mesenchymal
      stromal precursors. Moreover, transfected osteoprogenitors overexpressing IR-A
      show an increased proliferation rate. In contrast, when transfected with and
      overexpressing IR-B, their proliferation rate is reduced, corresponding to a more
      differentiated phenotype. In conclusion, the fine regulation of the expression of
      different isoforms of IR during osteogenic differentiation confirms the important
      role played by IR in bone homeostasis, providing the basis for new perspectives
      on the various involvements of IR isoforms in bone pathophysiology.

PMID- 22466606
TI  - Interosseous muscle atrophy.

PMID- 22466607
TI  - Post-bronchoalveolar lavage pneumothorax.

PMID- 22466605
TI  - Motor imagery and higher-level cognition: four hurdles before research can sprint
      forward.
AB  - Traditionally, higher-level cognition has been described as including processes
      such as attention, memory, language, and decision-making. However, motor
      processing and motor imagery are important aspects of cognition that have
      typically been considered outside of the traditional view. Recent research has
      demonstrated that there may be a critical functional relationship between motor
      imagery and other higher-level cognitive processes. Here we present a review of
      the extant literature on motor imagery and cognition, as well as outline four
      hurdles that must be addressed before the field investigating the influence of
      motor-based processes on higher-level cognition can be moved forward. These
      hurdles include problems distinguishing between visual and motor processes,
      addressing the differences in tasks and stimuli used to evoke motor imagery,
      accounting for individual differences in motor imagery ability, and identifying
      the appropriate neural correlates. It is important that these hurdles are
      addressed in future research so we can sprint forward and further our knowledge
      about this interesting relationship.

PMID- 22466609
TI  - Differential diagnoses of nocturnal fear and movement paroxysm: a case report.
AB  - Recurrent nocturnal behavioural and movement paroxysms are a diagnostic challenge
      for the clinical pediatrician. We report on an adolescent girl who presents
      recurrent stereotypical nightmare-like episodes occurring during non-REM sleep
      stages 1-2 (N1 and N2). We discuss the differential diagnoses between epileptic
      and nonepileptic events and between nocturnal frontal and temporal seizures. The
      pathophysiological and unusual electroencephalographical features are discussed
      with respect to clinical features and results of interictal FDG-PET. Conclusion
      In case of stereotypical nightmare-like episodes in children or adolescents, an
      epileptic origin has to be ruled out before a parasomnia is diagnosed. In
      addition, a normal awake EEG or interictal sleep EEG in the diagnostic workup may
      not exclude an epileptic disorder. In case of nightly stereotypic motor or
      affective events, an epileptic disorder should be discussed.

PMID- 22466610
TI  - Mutations in UVSSA cause UV-sensitive syndrome and impair RNA  polymerase IIo
      processing in transcription-coupled nucleotide-excision repair.
AB  - UV-sensitive syndrome (UV(S)S) is a genodermatosis characterized by cutaneous
      photosensitivity without skin carcinoma. Despite mild clinical features, cells
      from individuals with UV(S)S, like Cockayne syndrome cells, are very UV sensitive
      and are deficient in transcription-coupled nucleotide-excision repair (TC-NER),
      which removes DNA damage in actively transcribed genes. Three of the seven known
      UV(S)S cases carry mutations in the Cockayne syndrome genes ERCC8 or ERCC6 (also
      known as CSA and CSB, respectively). The remaining four individuals with UVSS ,
      one of whom is described for the first time here, formed a separate UV(S)S-A
      complementation group; however, the responsible gene was unknown. Using exome
      sequencing, we determine that mutations in the UVSSA gene (formerly known as
      KIAA1530) cause UV(S)S-A. The UVSSA protein interacts with TC-NER machinery and
      stabilizes the ERCC6 complex; it also facilitates ubiquitination of RNA
      polymerase IIo stalled at DNA damage sites. Our findings provide mechanistic
      insights into the processing of stalled RNA polymerase and explain the different
      clinical features across these TC-NER-deficient disorders.

PMID- 22466611
TI  - UV-sensitive syndrome protein UVSSA recruits USP7 to  regulate transcription
      coupled repair.
AB  - Transcription-coupled nucleotide-excision repair (TC-NER) is a subpathway of NER
      that efficiently removes the highly toxic RNA polymerase II blocking lesions in
      DNA. Defective TC-NER gives rise to the human disorders Cockayne syndrome and UV
      sensitive syndrome (UV(S)S). NER initiating factors are known to be regulated by
      ubiquitination. Using a SILAC-based proteomic approach, we identified UVSSA
      (formerly known as KIAA1530) as part of a UV-induced ubiquitinated protein
      complex. Knockdown of UVSSA resulted in TC-NER deficiency. UVSSA was found to be
      the causative gene for UV(S)S, an unresolved NER deficiency disorder. The UVSSA
      protein interacts with elongating RNA polymerase II, localizes specifically to UV
      induced lesions, resides in chromatin-associated TC-NER complexes and is
      implicated in stabilizing the TC-NER master organizing protein ERCC6 (also known
      as CSB) by delivering the deubiquitinating enzyme USP7 to TC-NER complexes.
      Together, these findings indicate that UVSSA-USP7-mediated stabilization of ERCC6
      represents a critical regulatory mechanism of TC-NER in restoring gene
      expression.

PMID- 22466612
TI  - Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6  in
      transcription-coupled DNA repair.
AB  - UV-sensitive syndrome (UV(S)S) is an autosomal recessive disorder characterized
      by photosensitivity and deficiency in transcription-coupled repair (TCR), a
      subpathway of nucleotide-excision repair that rapidly removes transcription
      blocking DNA damage. Cockayne syndrome is a related disorder with defective TCR
      and consists of two complementation groups, Cockayne syndrome (CS)-A and CS-B,
      which are caused by mutations in ERCC8 (CSA) and ERCC6 (CSB), respectively.
      UV(S)S comprises three groups, UV(S)S/CS-A, UV(S)S/CS-B and UV(S)S-A, caused by
      mutations in ERCC8, ERCC6 and an unidentified gene, respectively. Here, we report
      the cloning of the gene mutated in UV(S)S-A by microcell-mediated chromosome
      transfer. The predicted human gene UVSSA (formerly known as KIAA1530)(7) corrects
      defective TCR in UV(S)S-A cells. We identify three nonsense and frameshift UVSSA
      mutations in individuals with UV(S)S-A, indicating that UVSSA is the causative
      gene for this syndrome. The UVSSA protein forms a complex with USP7 (ref. 8),
      stabilizes ERCC6 and restores the hypophosphorylated form of RNA polymerase II
      after UV irradiation.

PMID- 22466613
TI  - Multiple apical plasma membrane constituents are associated with  susceptibility
      to meconium ileus in individuals with cystic fibrosis.
AB  - Variants associated with meconium ileus in cystic fibrosis were identified in
      3,763 affected individuals by genome-wide association study (GWAS). Five SNPs at
      two loci near SLC6A14 at Xq23-24 (minimum P = 1.28 * 10(-12) at rs3788766) and
      SLC26A9 at 1q32.1 (minimum P = 9.88 * 10(-9) at rs4077468) accounted for ~5% of
      phenotypic variability and were replicated in an independent sample of affected
      individuals (n = 2,372; P = 0.001 and 0.0001, respectively). By incorporating the
      knowledge that disease-causing mutations in CFTR alter electrolyte and fluid flux
      across surface epithelium into a hypothesis-driven GWAS (GWAS-HD), we identified
      associations with the same SNPs in SLC6A14 and SLC26A9 and established evidence
      for the involvement of SNPs in a third solute carrier gene, SLC9A3. In addition,
      GWAS-HD provided evidence of association between meconium ileus and multiple
      genes encoding constituents of the apical plasma membrane where CFTR resides (P =
      0.0002; testing of 155 apical membrane genes jointly and in replication, P =
      0.022). These findings suggest that modulating activities of apical membrane
      constituents could complement current therapeutic paradigms for cystic fibrosis.

PMID- 22466614
TI  - Clinical observation of immunity in patients with secondary infection from severe
      acute pancreatitis.
AB  - OBJECTIVES: To observe immune system changes in patients with secondary infection
      from severe acute pancreatitis (SAP). METHODS: Seventy-nine patients were
      recruited. The percentages of CD4+, CD8+, natural killer (NK), HLA-DR+ cells and
      B lymphocytes, and the CD4+/CD8+ ratio, were determined. In addition, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10),
      and interleukin-4 (IL-4) serum levels were determined on days 1, 7, 14, and 28.
      RESULTS: Fifteen patients had a secondary infection. The immune response of the
      infected group was quite different from the non-infected group, with a higher
      percentage of CD4+ and HLA-DR+ cells on days 1, 7, 14 and 28, a higher percentage
      of CD8+ and NK cells on days 14 and 28, a reduced CD4+/CD8+ ratio, and a
      reduction in B lymphocytes. The cytokine levels in the infected group were
      different from the non-infected group, with a rise in TNF-alpha and IL-6 through
      the first 2 weeks, but dropping at 1 month. IL-10 and IL-4 increased initially,
      but then dropped over the next 3 weeks. CONCLUSIONS: An early excessive immune
      response followed by a subsequent immune deficiency is closely related to
      secondary SAP infection.

PMID- 22466616
TI  - High-fidelity chemical patterning on oxide-free germanium.
AB  - Oxide-free germanium can be chemically patterned directly with self-assembled
      monolayers of n-alkanethiols via submerged microcontact printing. Native
      germanium dioxide is water soluble; immersion activates the germanium surface for
      self-assembly by stripping the oxide. Water additionally provides an effective
      diffusion barrier that prevents undesired ink transport. Patterns are stable with
      respect to molecular exchange by carboxyl-functionalized thiols.

PMID- 22466615
TI  - Water balance trumps ion balance for early marine survival of juvenile pink
      salmon (Oncorhynchus gorbuscha).
AB  - Smolting salmonids typically require weeks to months of physiological preparation
      in freshwater (FW) before entering seawater (SW). Remarkably, pink salmon
      (Oncorhynchus gorbuscha) enter SW directly following yolk absorption and gravel
      emergence at a size of 0.2 g. To survive this exceptional SW migration, pink
      salmon were hypothesized to develop hypo-osmoregulatory abilities prior to yolk
      absorption and emergence. To test this, alevins (pre-yolk absorption) and fry
      (post-yolk absorption) were transferred from FW in darkness to SW under simulated
      natural photoperiod (SNP). Ionoregulatory status was assessed at 0, 1 and 5 days
      post-transfer. SW alevins showed no evidence of hypo-osmoregulation, marked by
      significant water loss and no increase in gill Na+/K+-ATPase (NKA) activity or
      Na+:K+:2Cl- cotransporter (NKCC) immunoreactive (IR) cell frequency. Conversely,
      fry maintained water balance, upregulated gill NKA activity by 50 %, increased
      the NKA alpha1b/alpha1a mRNA expression ratio by sixfold and increased NKCC IR
      cell frequency. We also provide the first evidence of photoperiod-triggered
      smoltification in pink salmon, as fry exposed to SNP in FW exhibited preparatory
      changes in gill NKA activity and alpha1 subunit expression similar to fry exposed
      to SNP in SW. Interestingly, fry incurred larger increases in whole body Na+ than
      alevins following both SW and FW + SNP exposure (40 and 20 % in fry vs. 0 % in
      alevins). The ability to incur and tolerate large ion loads may underlie a novel
      mechanism for maintaining water balance in SW prior to completing hypo
      osmoregulatory development. We propose that pink salmon represent a new form of
      anadromy termed "precocious anadromy".

PMID- 22466617
TI  - Natural killer cell recognition and killing of activated hepatic stellate cells.

PMID- 22466618
TI  - Hyaluronan impairs vascular function and drug delivery in a mouse model of
      pancreatic cancer.
AB  - OBJECTIVE: Pancreatic ductal adenocarcinoma (PDA) is characterised by stromal
      desmoplasia and vascular dysfunction, which critically impair drug delivery. This
      study examines the role of an abundant extracellular matrix component, the
      megadalton glycosaminoglycan hyaluronan (HA), as a novel therapeutic target in
      PDA. METHODS: Using a genetically engineered mouse model of PDA, the authors
      enzymatically depleted HA by a clinically formulated PEGylated human recombinant
      PH20 hyaluronidase (PEGPH20) and examined tumour perfusion, vascular permeability
      and drug delivery. The preclinical utility of PEGPH20 in combination with
      gemcitabine was assessed by short-term and survival studies. RESULTS: PEGPH20
      rapidly and sustainably depleted HA, inducing the re-expansion of PDA blood
      vessels and increasing the intratumoral delivery of two chemotherapeutic agents,
      doxorubicin and gemcitabine. Moreover, PEGPH20 triggered fenestrations and
      interendothelial junctional gaps in PDA tumour endothelia and promoted a tumour
      specific increase in macromolecular permeability. Finally, combination therapy
      with PEGPH20 and gemcitabine led to inhibition of PDA tumour growth and prolonged
      survival over gemcitabine monotherapy, suggesting immediate clinical utility.
      CONCLUSIONS: The authors demonstrate that HA impedes the intratumoral vasculature
      in PDA and propose that its enzymatic depletion be explored as a means to improve
      drug delivery and response in patients with pancreatic cancer.

PMID- 22466619
TI  - Etiological distinctions between aggressive and non-aggressive antisocial
      behavior: results from a nuclear twin family model.
AB  - A recent meta-analysis of 103 studies Burt (Clinical Psychology Review, 29:163
      178, 2009a) highlighted the presence of etiological distinctions between
      aggressive (AGG) and non-aggressive rule-breaking (RB) dimensions of antisocial
      behavior, such that AGG was more heritable than was RB, whereas RB was more
      influenced by the shared environment. Unfortunately, behavioral genetic research
      on antisocial behavior to date (and thus, the research upon which the meta
      analysis was based) has relied almost exclusively on the classical twin model.
      This reliance is problematic, as the strict assumptions that undergird this model
      (e.g., shared environmental and dominant genetic influences are not present
      simultaneously; there is no assortative mating) can have significant consequences
      on heritability estimates when they are violated. The nuclear twin family model,
      by contrast, allows researchers to relax and statistically evaluate many of the
      assumptions of the classical twin design by incorporating parental self-report
      data along with the more standard twin data. The goal of the current study was
      thus to evaluate whether prior findings of etiological distinctions between AGG
      and RB persisted when using the nuclear twin family model. We examined a sample
      of 312 child twin families from the Michigan State University Twin Registry.
      Results strongly supported prior findings of etiological distinctions between AGG
      and RB, such that broad genetic influences were observed to be particularly
      important to AGG whereas shared environmental influences contributed only to RB.
      Nevertheless, the current findings also implied that additive genetic influences
      on antisocial behavior may be overestimated when using the classical twin design.

PMID- 22466620
TI  - Papillary tumor of the pineal region: a case involving isocitrate dehydrogenase
      (IDH) genotyping.
AB  - Papillary tumor of the pineal region (PTPR) is a recently described neoplasm.
      Several studies have been published on this tumor, but its pathological features
      and the appropriate treatment remain unclear. PTPR is reported to originate from
      ependymal cells in the subcommissural organ. Isocitrate dehydrogenase 1 and 2
      (IDH1/2) mutations have been a focus area in glioma research as promising
      predictors. We report a case of PTPR that was characterized by local recurrence,
      although subtotal removal and radiotherapy seemed effective for many months.
      Histological examination showed ependymal features in the surgical specimens. As
      far as we are aware, this case study is the first to show that the IDH1/2
      genotypes in PTPR cells are wild-type genotypes, which is consistent with the
      negative immunoreactivity that was observed for the IDH1 mutant antibody in this
      study.

PMID- 22466621
TI  - Light induced water oxidation on cobalt-phosphate (Co-Pi) catalyst modified semi
      transparent, porous SiO2-BiVO4 electrodes.
AB  - A facile and simple procedure for the synthesis of semi-transparent and porous
      SiO2-BiVO4 electrodes is reported. The method involves a surfactant assisted
      metal-organic decomposition at 500  degrees C. An earth abundant oxygen evolution
      catalyst (OEC), cobalt phosphate (Co-Pi), has been used to modify the SiO2-BiVO4
      electrode by electrodeposition (ED) and photoassisted electrodeposition (PED)
      methods. Modified electrodes by these two methods have been examined for light
      induced water oxidation and compared to the unmodified SiO2-BiVO4 electrodes by
      various photoelectrochemical techniques. The PED method was a more effective
      method of OEC preparation than the ED method as evidenced by an increased
      photocurrent magnitude during photocurrent-potential (I-V) characterizations.
      Electrode surfaces catalyzed by PED exhibited a very large cathodic shift (~420
      mV) in the onset potential for water oxidation. The chopped-light I-V
      measurements performed at different intervals over 24-hour extended testing under
      illumination and applied bias conditions show a fair photostability for PED Co-Pi
      modified SiO2-BiVO4. 

PMID- 22466622
TI  - Right pulmonary artery thrombosis after hybrid stage 1 palliation: resolution
      after direct tissue plasminogen activator infusion.
AB  - A patient with unbalanced right ventricular dominant atrioventricular septal
      defect with ascending and transverse arch hypoplasia underwent hybrid stage 1
      palliation. On postoperative day 7, he experienced irritability and acute
      cyanosis. Echocardiography demonstrated a thrombus occluding the right pulmonary
      artery band. Emergency cardiac catheterization confirmed thrombosis of the right
      pulmonary artery at the site of the band. Direct infusion of tissue plasminogen
      activator successfully lysed the thrombus.

PMID- 22466623
TI  - Decreased incidence of right-ventricular outflow tract complications using a
      retrograde snare technique for radiofrequency pulmonary valve perforation.
AB  - Perforation of the atretic pulmonary valve with balloon dilation in infants with
      pulmonary atresia with intact ventricular septum (PA-IVS) is standard initial
      therapy for right-ventricular (RV) decompression. This procedure often results in
      adequate pulmonary blood flow, thus eliminating the need for neonatal surgery.
      Nonetheless, the incidence of RV outflow-tract complications and mortality for
      this intervention is significant. We report our experience with retrograde snare
      guided radiofrequency (RF) perforation in an attempt to improve accuracy and
      decrease procedural complications. Medical records were reviewed for the period
      between March 2007 and May 2010 for all patients with PA-IVS who presented to the
      catheterization laboratory for attempted RF perforation in infancy. Specific
      details reviewed included demographics, preprocedural echocardiographic (echo)
      data, procedural technique and complications, pre- and post-RV pressures and
      pulmonary valve gradients, need for surgical intervention in the neonatal period,
      and short- to medium-term follow-up. Eleven neonates with PA-IVS underwent RF
      perforation using a retrograde snare-guided technique during the study period.
      The pulmonary valve was successfully perforated and the wire snared in all 11
      patients. Six of 11 atretic valves were crossed on the first attempt with low
      energy (5 W * 2 s). No episodes of tamponade or RV/PA perforation occurred as
      confirmed by echocardiogram performed immediately after the procedure. There was
      no ductal spasm with retrograde catheter manipulations. Sequential dilation of
      the perforated valve was not necessary. RV pressures decreased from 169 %
      systemic before dilation to 93 % after dilation (p < 0.001) with a residual
      pulmonary valve gradient of 16 +/- 6 mm Hg. Eight of 11 patients (73 %) were
      discharged without surgery at an average 16 days after the intervention. Three
      patients required Blalock-Taussig shunts to augment pulmonary blood flow. Femoral
      artery thrombus occurred in 4 of 11 patients treated with anticoagulation, and 2
      patients had atrial arrhythmias during the procedure. No other complications
      occurred. No preprocedural echo parameters predicted requirement for surgical
      shunt before hospital discharge. Retrograde snare-guided pulmonary valve
      perforation in infants with PA-IVS is safe and may decrease the incidence of
      significant procedural complications.

PMID- 22466625
TI  - Ancient greek philosophy and modern psychiatry.

PMID- 22466624
TI  - Analysis and enhancement of nutritional and antioxidant properties of Vigna
      aconitifolia sprouts.
AB  - Vigna aconitifolia sprouts (Moth bean sprouts, MBS) were analyzed for their
      nutritional and antioxidant properties during sprouting. Sprouting for six days
      led to a 7.0 fold increase in fresh weight, 2.4 fold increase in soluble
      proteins, 3.0 fold increase in carbohydrates, and a 5.5 fold increase in mineral
      content. Phenolic content also increased by 28% during germination. Caffeic acid,
      ferulic acid, cinnamic acid and kaempferol were the predominant phenolic
      compounds detected in the ethanolic extracts of MBS by HPLC. Following
      supplementation with metal ions (200 MUg ml-1), the sprouts demonstrated a
      considerable increase in metal ion uptake, with improved phenolic content. MBS
      ethanolic extracts also reduced intracellular oxidative stress in HepG2 cells.

PMID- 22466626
TI  - [Hospital anxiety and depression scale (HADS): Validation in a Greek general
      hospital sample].
AB  - The Hospital Anxiety and Depression Scale (HADS) has been translated and widely
      used in several countries to assess anxiety and depression in general hospital
      patients with good results. Material-Method The HADS was administered to 521
      participants (275 controls and 246 inpatients and outpatients of Internal
      Medicine and Surgical Departments). The Beck Depression Inventory (BDI) and the
      State-Trait Anxiety Inventory (STAI) were used as "gold standards" for depression
      and anxiety respectively. Results The HADS presented high internal consistency;
      Cronbach's alpha=0.884 (0.829 for anxiety and 0.840 for depression) and stability
      (test-retest Intraclass Correlation Coefficient 0.944). Factor analysis showed a
      two-factor structure. The HADS showed high concurrent validity; the correlations
      of the scale and its subscales with the BDI and the STAI were high (0.722-0.749).
      CONCLUSIONS: The Greek version of HADS showed good psychometric properties and
      could prove as a good tool for clinicians to assess anxiety and depression in
      general hospital patients.

PMID- 22466627
TI  - [The neurobiology of autism].
AB  - The research effort on autism has for several years been intensive. Recent
      progress in this field is due mainly to the development of increasingly
      sophisticated visualizing assessment methods of the brain. Most of the evidence
      reported in this review requires further replication and elaboration by ongoing
      research. Evidence from volumetric studies indicates that the brain of the child
      with autism deviates from normal paths at the early stages of development showing
      excessive growth during the first year and a half involving the hemispheres and
      the cerebellum. Post mortem studies have shown neuron abnormalities in the
      frontal and temporal cortex and the cerebellum. Studies using diffusion tensor
      imaging, an fMRI based method, have shown disruptions between white and grey
      matter in several areas of the hemispheres. Other studies investigating
      activation of the cortex showed lack of synchrony and coordination between
      anterior and posterior areas of the hemispheres. It has been suggested that the
      deviation in brain development in autism consists of excessive numbers of neurons
      which cause the cytoarchitectural deviation. A theory suggesting that the basic
      deficit in autism is due to dysfunction of the "mirror neuron system" requires
      further substantiation. The aetiology of autism is not known although risk
      factors have been identified. Predominant among them are genetic influences. The
      search is currently intensive for an understanding of the pathogenesis of the
      pathological deviation in the development of the brain in autism. Neurotrophic
      factors which determine the developmental steps of the brain are examined such as
      serotonin, brain-derived neurotrophic factor (BDNF), the neuropeptide reelin,
      neuroligines and others. There is evidence of some involvement of these factors
      with autism but it is still far from clear how they do interact with one another
      and how they lead to the pathological deviations observed in autism. The
      neurotrophic factors are evidently coded by genes which are being examined by
      geneticists. It has also been suggested that autoimmune responses while
      interacting with neurotrophic factors may be important for the autistic deviation
      in brain development. Limitations may exist in the interpretation of the study
      results on which the present review was based. These are probably due to
      inconsistencies among studies related to variability in the severity of the
      disorders and age among subjects, presence or not of mental retardation,
      differing assessment methods.

PMID- 22466628
TI  - ["Continuum" and "Spectrum" hypotheses of depressive disorders].
AB  - Nowadays, the acceptance of depressive disorders as distinct entities in a
      categorical system with clearly defined diagnostic criteria has been considered
      by many researchers to be dysfunctional and stringent. An increasing number of
      patients with mild depressive symptomatology and dysfunction, who do not satisfy
      specific diagnostic criteria, seek help in primary care settings. Many questions
      arise in relation to whether contemporary categories of depressive disorders
      categories adequately reflect the broad spectrum of depressive disorders
      occurring in the general population. Contemporary classification-categorization
      systems are based on the development of diagnostic categories using a "threshold"
      that defines the subjective dimensional depressive spectrum. However, the so
      called categorical or "threshold" diagnostic system of depressive disorders is
      nowadays open to skepticism. According to the "continuum" hypothesis, depressive
      disorders extend from normality up to exceptionally disturbed symptomatology
      (i.e. major depression) and behaviour (i.e. suicidality). Moreover, the
      "spectrum" of depressive disorders includes a variety of signs and symptoms,
      extending from the core depressive symptoms to temperament characteristics. These
      symptoms and/or signs could manifest during a depressive episode, between
      depressive episodes, or even in the absence of depressive episodes. Many
      researchers argue that subthreshold (subsyndromal) depressive symptoms may be
      prodromal or residual manifestations of depressive episodes, or may represent
      early stages of the continuum of major depressive disorders. The continuum and
      the spectrum hypotheses of depression could be especially beneficial to the
      development of primary care prevention programms. However, various concerns have
      been expressed in relation to the depressive continuum and spectrum hypotheses.
      Such arguments include the decrease of the reliability and validity of the
      depression diagnosis, as well as the need for introduction of new subgroup
      categories of depressive disorders, based on special symptoms (i.e. typical or
      atypical depression). The lack of specific psychometric instruments measuring
      subthreshold symptoms should also be considered. The above hypotheses of
      depressive disorders require further theoretical elaboration and confirmation by
      systematic research studies.

PMID- 22466629
TI  - [Narcissism and religiosity].
AB  - The author attempts a selective review of the concept of narcissism from Freud
      and its development from the theorists of objects relationships. He also
      describes the religiosity in the psychopathology and in every day life and at
      last he discusses how the defense structure of narcissism and religiosity
      interweaved and restrained the capability of the subject to love and create.
      There are used vignettes from the psychoanalysis of three patients and an
      allegory from the New Testament. The author suggests that the passing through the
      paranoid-schizoid to the depressive position helps the narcissistic personality
      to free itself not only of persecutory anxieties but also of depressive anxieties
      and to complete mourning. In this position he no needs any more to use the
      religion to protect himself from his pain but he can use it to "know" the other.

PMID- 22466630
TI  - [Use of antiepileptic drugs in schizophrenia: A review of recent evidence].
AB  - The treatment of schizophrenia has always been a challenge for clinicians.
      Neuroleptic monotherapy is not sufficient in all subtypes and all symptoms of
      schizophrenia. New treatment strategies have been developed including the
      combination of neuroleptics and antiepileptics. We summarize papers published on
      the efficacy and the action mechanism of antiepileptic agents in schizophrenia.
      We have searched the computer database system MEDLINE and COCHRANE for relevant
      articles. GABA and glutamate are involved in the symptom improvement of
      schizophrenia when antiepileptics are added in the main neuroleptic treatment.
      Augmentation treatment with valproate leads to a decrease in hostility, violent
      behavior, agitation and anxiety and is related to fewer days of hospitalization.
      Carbamazepine has been used as a calmative and is effective in controlling
      patients with psychomotor agitation. Whether both antiepileptics can reduce
      positive and negative symptoms in schizophrenia, still remains controversial.
      Oxcarbazepine has a very safe pharmaceutical profile in combination with
      neuroleptics but only a single study indicates its efficacy. Adjunctive
      lamotrigine appears effective when added to clozapine even in cases of treatment
      resistant schizophrenia. Both lamotrigine and clozapine share anti-glutamatergic
      actions. There have been reported few studies which support the use of topiramate
      in schizophrenia. Future studies on a great number of patients will provide more
      reliable evidence. Finally the potential role of new antiepileptics has to be
      evaluated using new clinical testing.

PMID- 22466631
TI  - [Neuroleptic malignant syndrome and atypical antipsychotics: two case reports].
AB  - Neuroleptic malignant syndrome (NMS) constitutes the most serious adverse effect
      of antipsychotic medications. Although it was initially described as a
      complication of conventional neuroleptics, atypical antipsychotic agents are also
      capable of inducing the syndrome. It has been suggested that atypical
      antipsychotic-induced NMS may be qualitatively and quantitatively different from
      the NMS caused by conventional neuroleptics; however, atypical antipsychotics can
      also be associated with severe forms of NMS. We report two patients who
      manifested severe NMS in association with atypical antipsychotic agents. Both
      patients were receiving low antipsychotic doses; moreover, one of the patients
      had not undergone any recent changes in his antipsychotic regimen. Thus, it is
      pointed out that vigilance for signs of NMS should not be influenced by
      antipsychotic type and dose.

PMID- 22466632
TI  - Is anterior cervical fusion with a porous tantalum implant a cost-effective
      method to treat cervical disc disease with radiculopathy?
AB  - STUDY DESIGN: Retrospective cost-effectiveness analysis. OBJECTIVE: To determine
      the relative cost-effectiveness of anterior cervical discectomy with fusion
      (ACDF) using a porous tantalum implant compared with autograft with plating, for
      single-level cervical disc disease with radiculopathy. SUMMARY OF BACKGROUND
      DATA: ACDF with autograft as an interbody spacer is a generally accepted method
      to treat degenerated cervical discs with radiculopathy. Concerns about donor site
      morbidity and the structural characteristics of autograft stimulated
      investigations of alternative materials. Techniques may differ in their operative
      risks, complications, outcomes, and resource use. METHODS: A retrospective review
      of clinical outcomes and total cost of illness for 5 years postsurgery was
      performed for 61 consecutive patients enrolled for this study. Twenty-eight
      patients were treated with single-level ACDF using either a stand-alone, porous
      tantalum implant, without graft inside the implant, and 33 patients received
      autograft and plating. A cost-effectiveness analysis comparing the 2 ACDF
      treatment methods was conducted. This article reports clinical assessments,
      quality adjusted life years gained, and an incremental cost-effectiveness ratio
      analysis. RESULTS: Patients in both cohorts reported improved clinical outcomes,
      including neck disability index, visual analogue scale, Short-Form 36, Odom's
      clinical assessment, and patient satisfaction at 5 years postindex surgery. The
      mean cost of illness for the study period, including preoperative through 5 years
      postoperative assessments, was 6806 per patient treated with tantalum and 10,143
      per patient receiving autograft and plate. Quality-adjusted life years (QALY)
      gained were 9.41 and 7.14 for the tantalum and control cohorts, respectively. The
      cost per QALY for the tantalum group was 723 and 1420 for the control group. The
      incremental cost-effectiveness ratio of ACDF with a porous tantalum implant
      compared with ACDF with autograft and plate was -1473 per patient per year for
      the duration of this study. CONCLUSION: This cost-effectiveness analysis reports
      favorable results for ACDF procedures utilizing a tantalum implant. The data
      reported suggest that using porous tantalum as a stand-alone device is less
      costly and more effective than autograft and plate in ACDF procedures.

PMID- 22466633
TI  - Mechanisms for enhanced endothelium-derived hyperpolarizing factor-mediated
      responses in microvessels in mice.
AB  - BACKGROUND: Endothelium-derived relaxing factors play an important role in
      cardiovascular homeostasis. Among them, endothelium-derived hyperpolarizing
      factor (EDHF) is important especially in microcirculation. It has previously been
      demonstrated that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in
      animals and humans and that endothelial nitric oxide synthase (eNOS) plays
      diverse roles as a nitric oxide (NO) generating system in conduit arteries and as
      an EDHF/H(2)O(2) generating system in microvessels. As compared with NO-mediated
      responses, those by EDHF are resistant to atherosclerosis, contributing to the
      maintenance of cardiovascular homeostasis. The aim of this study is to elucidate
      the molecular mechanisms for enhanced EDHF-mediated responses in microvessels.
      METHODS AND RESULTS: This study used male wild-type mice and caveolin-1-deficient
      mice (caveolin-1(-/-) mice). In the endothelium, eNOS was functionally suppressed
      in mesenteric arteries (microvessels) compared with the aorta (conduit arteries),
      for which Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) and
      caveolin-1 are involved, as EDHF-mediated responses were inhibited by STO-609 (an
      inhibitor of CaMKKbeta) and in caveolin-1(-/-) mice, respectively. In vascular
      smooth muscle, relaxation responses to H(2)O(2) were enhanced through a protein
      kinase G1alpha (PKG1alpha)-mediated mechanism in mesenteric arteries compared
      with the aorta, as they were inhibited by Rp-8-Br-cGMPS (an inhibitor of
      PKG1alpha). CONCLUSIONS: These results indicate that CaMKKbeta, caveolin-1, and
      PKG1alpha are substantially involved in the mechanisms for the enhanced EDHF
      mediated responses in microvessels in mice.

PMID- 22466634
TI  - How long can we leave patients with pulmonary arterial hypertension on oral drug
      monotreatment?

PMID- 22466635
TI  - Bio-image informatics.

PMID- 22466636
TI  - Specific effects of endurance and sprint training on protein expression of
      calsequestrin and SERCA in mouse skeletal muscle.
AB  - Calsequestrin (CSQ) is the main Ca2+ binding protein inside the sarcoplasmic
      reticulum (SR) of skeletal and cardiac muscle. The present study demonstrates the
      specific effects of different training regimens on CSQ isoform 1 (CSQ1, the
      primary isoform) and SR Ca2+-ATPase (SERCA1, 2) expression in various skeletal
      muscles of mouse. CSQ1, SERCA1, and SERCA2 protein expression was determined with
      Western blot in m. soleus (SOL), m. extensor digitorum longus (EDL), m.
      gastrocnemius (GAS), m. rectus femoris (RF), and m. tibialis anterior (TA)
      muscles after completing a 6-week endurance or sprint training program. Endurance
      training induced decrease in CSQ1 concentration in SOL (p < 0.001) and in SERCA1
      levels in GAS (p < 0.05), whereas increase in CSQ1 expression was detected in EDL
      (p < 0.01). After sprint training the concentration of CSQ1 increased in GAS (p <
      0.01) and EDL (p < 0.01). Additionally, sprint exercise induced an increase in
      SERCA1 in GAS (p < 0.001) and a decline in TA (p < 0.05). SERCA2 was up-regulated
      with sprint training in GAS (p < 0.01). Myosin heavy chain (MHC) based fibre type
      composition altered differently depending on the muscle and the training
      regimen.These results indicate that (1) diverse training strategies used affect
      differently CSQ1 and SERCA1 concentrations in the skeletal muscle, (2) the
      regulation of CSQ1 and SERCA1 does not necessary follow the fast-slow definition
      despite the correlation between MHC isoforms, and (3) the changes in CSQ1
      concentration occur prior to SERCA1 or SERCA2.

PMID- 22466643
TI  - Association of cytokeratin 17 expression with differentiation in oral squamous
      cell carcinoma.
AB  - PURPOSE: The aim of this study was to confirm the expression profile of
      cytokeratin (CK)17 in comparison with that of CK13 in oral squamous cell
      carcinoma (OSCC) and leukoplakia and to clarify an association of CK17 with the
      OSCC differentiation. MATERIALS: The expression of CK17 and CK13 was
      immunohistochemically examined in 105 patients with OSCC and 108 patients with
      leukoplakia. A correlation of CK expression with clinicopathological variables
      was carried out. The over-expression levels of CK17 mRNA were analyzed by real
      time RT-PCR in 5 OSCC cell lines (HSC-2, HSC-3, SAS, SQUU-A, SQUU-B). RESULTS:
      CK17 and CK13 were detected in 101 (96.2 %) and three (2.9 %) of the 105 OSCCs,
      respectively. CK17 was significantly expressed in well-differentiated OSCC
      compared to moderately/poorly differentiated OSCC (p < 0.01). As detected in 19
      of the 34 dysplastic leukoplakias (55.9 %) and 36 of the 74 hyperplastic
      leukoplakias (48.6 %), CK17 was significantly expressed in dysplastic
      leukoplakias (p < 0.01). As detected in 11 of the 34 dysplastic (32.4 %) and 52
      of the 74 hyperplastic leukoplakias (70.3 %), CK13 was significantly expressed in
      hyperplastic leukoplakias (p < 0.01). The relative expression of CK17 mRNA in HSC
      2 was significantly higher than in HSC-3 and SAS (p < 0.05). Moreover, the
      relative expression of CK17 mRNA in SQUU-A was significantly higher than in SQUU
      B (p < 0.05). CONCLUSION: CK17 expression could be associated with the
      differentiation and the malignancy of OSCC. A combination pattern of CK17/CK13
      might be a suitable marker of malignant transformation.

PMID- 22466645
TI  - Revertant mosaicism in a human skin fragility disorder results from slipped
      mispairing and mitotic recombination.
AB  - Spontaneous gene repair, also called revertant mosaicism, has been documented in
      several genetic disorders involving organs that undergo self-regeneration,
      including the skin. Genetic reversion may occur through different mechanisms, and
      in a single individual, the mutation can be repaired in various ways. Here we
      describe a disseminated pattern of revertant mosaicism observed in 6 patients
      with Kindler syndrome (KS), a genodermatosis caused by loss of kindlin-1 (encoded
      by FERMT1) and clinically characterized by patchy skin pigmentation and atrophy.
      All patients presented duplication mutations (c.456dupA and c.676dupC) in FERMT1,
      and slipped mispairing in direct nucleotide repeats was identified as the
      reversion mechanism in all investigated revertant skin spots. The sequence around
      the mutations demonstrated high propensity to mutations, favoring both
      microinsertions and microdeletions. Additionally, in some revertant patches,
      mitotic recombination generated areas with homozygous normal keratinocytes.
      Restoration of kindlin-1 expression led to clinically and structurally normal
      skin. Since loss of kindlin-1 severely impairs keratinocyte proliferation, we
      predict that revertant cells have a selective advantage that allows their clonal
      expansion and, consequently, the improvement of the skin condition.

PMID- 22466646
TI  - MyD88 is critically involved in immune tolerance breakdown at environmental
      interfaces of Foxp3-deficient mice.
AB  - Tregs expressing the transcription factor Foxp3 suppress self-reactive T cells,
      prevent autoimmunity, and help contain immune responses to foreign antigens,
      thereby limiting the potential for inadvertent tissue damage. Mutations in the
      FOXP3 gene result in Treg deficiency in mice and humans, which leads to the
      development of a multisystem autoimmune inflammatory disease. The contribution of
      dysregulated innate immune responses to the pathogenesis of Foxp3 deficiency
      disease is unknown. In this study, we examined the role of microbial signals in
      the pathogenesis of Foxp3 deficiency disease by studying Foxp3 mutant mice that
      had concurrent deficiencies in TLR signaling pathways. Global deficiency of the
      common TLR adaptor MyD88 offered partial protection from Foxp3 deficiency
      disease. Specifically, it protected from disease at the  environmental interfaces
      of the skin, lungs, and gut. In contrast, systemic disease, in the form of
      unrestrained lymphoproliferation, continued unabated. The effect of MyD88
      deficiency at environmental interfaces involved the disruption of chemokine
      gradients that recruit effector T cells and DCs, resulting in their entrapment in
      secondary lymphoid tissues. These results suggests that Tregs have a key role in
      maintaining tolerance at host-microbial interfaces by restraining tonic MyD88
      dependent proinflammatory signals. Moreover, microbial factors may play a
      substantial role in the pathogenesis of human autoimmune disease resulting from
      Treg deficiency.

PMID- 22466647
TI  - SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse
      models of breast cancer.
AB  - An association between lymph node metastasis and poor prognosis in breast cancer
      was observed decades ago. However, the mechanisms by which tumor cells infiltrate
      the lymphatic system are not completely understood. Recently, it has been
      proposed that the lymphatic system has an active role in metastatic dissemination
      and that tumor-secreted growth factors stimulate lymphangiogenesis. We therefore
      investigated whether SIX1, a homeodomain-containing transcription factor
      previously associated in breast cancer with lymph node positivity, was involved
      in lymphangiogenesis and lymphatic metastasis. In a model in which human breast
      cancer cells were injected into immune-compromised mice, we found that SIX1
      expression promoted peritumoral and intratumoral lymphangiogenesis, lymphatic
      invasion, and distant metastasis of breast cancer cells. SIX1 induced
      transcription of the prolymphangiogenic factor VEGF-C, and this was required for
      lymphangiogenesis and lymphatic metastasis. Using a mouse mammary carcinoma
      model, we found that VEGF-C was not sufficient to mediate all the metastatic
      effects of SIX1, indicating that SIX1 acts through additional, VEGF-C-independent
      pathways. Finally, we verified the clinical significance of this prometastatic
      SIX1/VEGF-C axis by demonstrating coexpression of SIX1 and VEGF-C in human breast
      cancer. These data define a critical role for SIX1 in lymphatic dissemination of
      breast cancer cells, providing a direct mechanistic explanation for how VEGF-C
      expression is upregulated in breast cancer, resulting in lymphangiogenesis and
      metastasis.

PMID- 22466648
TI  - CD14 and NFAT mediate lipopolysaccharide-induced skin edema formation in mice.
AB  - Inflammation is a multistep process triggered when innate immune cells - for
      example, DCs - sense a pathogen or injured cell or tissue. Edema formation is one
      of the first steps in the inflammatory response; it is fundamental for the local
      accumulation of inflammatory mediators. Injection of LPS into the skin provides a
      model for studying the mechanisms of inflammation and edema formation. While it
      is known that innate immune recognition of LPS leads to activation of numerous
      transcriptional activators, including nuclear factor of activated T cells (NFAT)
      isoforms, the molecular pathways that lead to edema formation have not been
      determined. As PGE2 regulates many proinflammatory processes, including swelling
      and pain, and it is induced by LPS, we hypothesized that PGE2 mediates the local
      generation of edema following LPS exposure. Here, we show that tissue-resident
      DCs are the main source of PGE2 and the main controllers of tissue edema
      formation in a mouse model of LPS-induced inflammation. LPS exposure induced
      expression of microsomal PGE synthase-1 (mPGES-1), a key enzyme in PGE2
      biosynthesis. mPGES-1 activation, PGE2 production, and edema formation required
      CD14 (a component of the LPS receptor) and NFAT. Therefore, tissue edema
      formation induced by LPS is DC and CD14/NFAT dependent. Moreover, DCs can
      regulate free antigen arrival at the draining lymph nodes by controlling edema
      formation and interstitial fluid pressure in the presence of LPS. We therefore
      suggest that the CD14/NFAT/mPGES-1 pathway represents a possible target for
      antiinflammatory therapies.

PMID- 22466649
TI  - Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice.
AB  - Radiation gastrointestinal (GI) syndrome is a major lethal toxicity that may
      occur after a radiation/nuclear incident. Currently, there are no prophylactic
      countermeasures against radiation GI syndrome lethality for first responders,
      military personnel, or remediation workers entering a contaminated area. The
      pathophysiology of this syndrome requires depletion of stem cell clonogens (SCCs)
      within the crypts of Lieberkuhn, which are a subset of cells necessary for
      postinjury regeneration of gut epithelium. Recent evidence indicates that SCC
      depletion is not exclusively a result of DNA damage but is critically coupled to
      ceramide-induced endothelial cell apoptosis within the mucosal microvascular
      network. Here we show that ceramide generated on the surface of endothelium
      coalesces to form ceramide-rich platforms that transmit an apoptotic signal.
      Moreover, we report the generation of 2A2, an anti-ceramide monoclonal antibody
      that binds to ceramide to prevent platform formation on the surface of irradiated
      endothelial cells of the murine GI tract. Consequently, we found that 2A2
      protected against endothelial apoptosis in the small intestinal lamina propria
      and facilitated recovery of crypt SCCs, preventing the death of mice from
      radiation GI syndrome after high radiation doses. As such, we suggest that 2A2
      represents a prototype of a new class of anti-ceramide therapeutics and an
      effective countermeasure against radiation GI syndrome mortality.

PMID- 22466650
TI  - Hepatocyte-specific mutation of both NF-kappaB RelA and STAT3 abrogates the acute
      phase response in mice.
AB  - The acute phase response is an evolutionarily conserved reaction in which
      physiological stress triggers the liver to remodel the blood proteome. Although
      thought to be involved in immune defense, the net biological effect of the acute
      phase response remains unknown. As the acute phase response is stimulated by
      diverse cytokines that activate either NF-kappaB or STAT3, we hypothesized that
      it could be eliminated by hepatocyte-specific interruption of both transcription
      factors. Here, we report that the elimination in mice of both NF-kappaB p65
      (RelA) and STAT3, but neither alone, abrogated all acute phase responses
      measured. The failure to respond was consistent across multiple different
      infectious, inflammatory, and noxious stimuli, including pneumococcal pneumonia.
      When the effects of infection were analyzed in detail, pneumococcal pneumonia was
      found to alter the expression of over a thousand transcripts in the liver. This
      outcome was inhibited by the combined loss of RelA and STAT3. Moreover, this
      interruption of the acute phase response increased mortality and exacerbated
      bacterial dissemination during pneumonia, possibly as a result of acute humoral
      enhancement of macrophage opsonophagocytosis, which was impaired in the mutant
      mice. Thus, we conclude that RelA and STAT3 are essential for stress-induced
      transcriptional remodeling in the liver and the subsequent activation of the
      acute phase response, whose functional role includes compartmentalization of
      local infection.

PMID- 22466651
TI  - Aberrant nuclear localization of EBP50 promotes colorectal carcinogenesis in
      xenotransplanted mice by modulating TCF-1 and beta-catenin interactions.
AB  - Dysregulation of canonical Wnt signaling is thought to play a role in colon
      carcinogenesis. beta-Catenin, a key mediator of the pathway, is stabilized upon
      Wnt activation and accumulates in the nucleus, where it can interact with the
      transcription factor T cell factor (TCF) to transactivate gene expression. Normal
      colonic epithelia express a truncated TCF-1 form, called dnTCF-1, that lacks the
      critical beta-catenin-binding domain and behaves as a transcriptional suppressor.
      How the cell maintains a balance between the two forms of TCF-1 is unclear. Here,
      we show that ERM-binding phosphoprotein 50 (EBP50) modulates the interaction
      between beta-catenin and TCF-1. We observed EBP50 localization to the nucleus of
      human colorectal carcinoma cell lines at low cell culture densities and human
      primary colorectal tumors that manifested a poor clinical outcome. In contrast,
      EBP50 was primarily membranous in confluent cell lines. Aberrantly located EBP50
      stabilized conventional beta-catenin/TCF-1 complexes and connected beta-catenin
      to dnTCF-1 to form a ternary molecular complex that enhanced Wnt/beta-catenin
      signaling events, including the transcription of downstream oncogenes such as c
      Myc and cyclin D1. Genome-wide analysis of the EBP50 occupancy pattern revealed
      consensus binding motifs bearing similarity to Wnt-responsive element.
      Conventional chromatin immunoprecipitation assays confirmed that EBP50 bound to
      genomic regions highly enriched with TCF/LEF binding motifs. Knockdown of EBP50
      in human colorectal carcinoma cell lines compromised cell cycle progression,
      anchorage-independent growth, and tumorigenesis in nude mice. We therefore
      suggest that nuclear EBP50 facilitates colon tumorigenesis by modulating the
      interaction between beta-catenin and TCF-1.

PMID- 22466653
TI  - Great expectations.
AB  - On the occasion of the 200th anniversary of Charles Dickens's birth, I am struck
      by his creative genius and by the parallel between the intellectual development
      of his protagonists and the evolution of peer review. Like many of his novels and
      serial writings, the story of the history of peer review is a bildungsroman, one
      that has followed a process of growing up, sought answers through a journey
      marked by achievement and disappointment, and ultimately matured to be accepted
      by a community.

PMID- 22466652
TI  - Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese
      mice.
AB  - Recent GWAS have identified SNPs at a human chromosom1 locus associated with
      coronary artery disease risk and LDL cholesterol levels. The SNPs are also
      associated with altered expression of hepatic sortilin-1 (SORT1), which encodes a
      protein thought to be involved in apoB trafficking and degradation. Here, we
      investigated the regulation of Sort1 expression in mouse models of obesity. Sort1
      expression was markedly repressed in both genetic (ob/ob) and high-fat diet
      models of obesity; restoration of hepatic sortilin-1 levels resulted in reduced
      triglyceride and apoB secretion. Mouse models of obesity also exhibit increased
      hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER
      stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob
      mice reduced ER stress and increased hepatic sortilin-1 levels. Conversely,
      genetically increased hepatic mTORC1 activity was associated with repressed Sort1
      and increased apoB secretion. Treating WT mice with the ER stressor tunicamycin
      led to marked repression of hepatic sortilin-1 expression, while administration
      of the chemical chaperone PBA to ob/ob mice led to amelioration of ER stress,
      increased sortilin-1 expression, and reduced apoB and triglyceride secretion.
      Moreover, the ER stress target Atf3 acted at the SORT1 promoter region as a
      transcriptional repressor, whereas knockdown of Atf3 mRNA in ob/ob mice led to
      increased hepatic sortilin-1 levels and decreased apoB and triglyceride
      secretion. Thus, in mouse models of obesity, induction of mTORC1 and ER stress
      led to repression of hepatic Sort1 and increased VLDL secretion via Atf3. This
      pathway may contribute to dyslipidemia in metabolic disease.

PMID- 22466654
TI  - Chromosomal instability and cancer: a complex relationship with therapeutic
      potential.
AB  - Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its
      widespread prevalence, knowledge of the mechanisms and contributions of CIN in
      cancer has been elusive. It is now evident that the role of CIN in tumor
      initiation and growth is more complex than previously thought. Furthermore,
      distinguishing CIN, which consists of elevated rates of chromosome
      missegregation, from aneuploidy, which is a state of abnormal chromosome number,
      is crucial to understanding their respective contributions in cancer.
      Collectively, experimental evidence suggests that CIN enables tumor adaptation by
      allowing tumors to constantly sample the aneuploid fitness landscape. This
      complex relationship, together with the potential to pharmacologically influence
      chromosome missegregation frequencies in cancer cells, offers previously
      unrecognized means to limit tumor growth and its response to therapy.

PMID- 22466655
TI  - Lessons learned at the intersection of immunology and neuroscience.
AB  - Neurobiologists and immunologists study concepts often signified with identical
      terminology. Scientists in both fields study a structure known as the synapse,
      and each group analyzes a subject called memory. Is this a quirk of human
      language, or are there real similarities between these two physiological systems?
      Not only are the linguistic concepts expressed in the words "synapse" and
      "memory" shared between the fields, but the actual molecules of physiologic
      importance in one system play parallel roles in the other: complement, the major
      histocompatibility molecules, and even "neuro"-transmitters all have major
      impacts on health and on disease in both the brain and the immune system. Not
      only are the same molecules found in diverse roles in each system, but we have
      learned that there is real "hard-wired" crosstalk between nerves and lymphoid
      organs. This issue of the JCI highlights some of the lessons learned from experts
      who are working at this scintillating intersection between immunology and
      neuroscience.

PMID- 22466656
TI  - Signaling at neuro/immune synapses.
AB  - Immunological and neural synapses share properties such as the synaptic cleft,
      adhesion molecules, stability, and polarity. However, the mismatch in scale has
      limited the utility of these comparisons. The discovery of phosphatase micro
      exclusion from signaling elements in immunological synapses and innate phagocytic
      synapses define a common functional unit at a common sub-micron scale across
      synapse types. Bundling of information from multiple antigen receptor
      microclusters by an immunological synapse has parallels to bundling of multiple
      synaptic inputs into a single axonal output by neurons, allowing integration and
      coincidence detection. Bonafide neuroimmune synapses control the inflammatory
      reflex. A better understanding of the shared mechanisms between immunological and
      neural synapses could aid in the development of new therapeutic modalities for
      immunological, neurological, and neuroimmunological disorders alike.

PMID- 22466657
TI  - The immunology of neurodegeneration.
AB  - While immune responses in neurodegeneration were regarded as little more than a
      curiosity a decade ago, they are now increasingly moving toward center stage.
      Factors driving this movement include the recognition that most of the relevant
      immune molecules are produced within the brain, that microglia are proficient
      immune cells shaping neuronal circuitry and fate, and that systemic immune
      responses affect brain function. We will review this complex field from the
      perspective of neurons, extra-neuronal brain cells, and the systemic environment
      and highlight the possibility that cell intrinsic innate immune molecules in
      neurons may function in neurodegenerative processes.

PMID- 22466658
TI  - Innate immunity in the central nervous system.
AB  - Immune responses in the CNS are common, despite its perception as a site of
      immune privilege. These responses can be mediated by resident microglia and
      astrocytes, which are innate immune cells without direct counterparts in the
      periphery. Furthermore, CNS immune reactions often take place in virtual
      isolation from the innate/adaptive immune interplay that characterizes peripheral
      immunity. However, microglia and astrocytes also engage in significant cross-talk
      with CNS-infiltrating T cells and other components of the innate immune system.
      Here we review the cellular and molecular basis of innate immunity in the CNS and
      discuss what is known about how outcomes of these interactions can lead to
      resolution of infection, neurodegeneration, or neural repair depending on the
      context.

PMID- 22466659
TI  - The adaptive immune system in diseases of the central nervous system.
AB  - Tissues of the CNS, such as the brain, optic nerves, and spinal cord, may be
      affected by a range of insults including genetic, autoimmune, infectious, or
      neurodegenerative diseases and cancer. The immune system is involved in the
      pathogenesis of many of these, either by causing tissue damage or alternatively
      by responding to disease and contributing to repair. It is clearly vital that
      cells of the immune system patrol the CNS and protect against infection. However,
      in contrast to other tissues, damage caused by immune pathology in the CNS can be
      irreparable. The nervous and immune systems have, therefore, coevolved to permit
      effective immune surveillance while limiting immune pathology. Here we will
      consider aspects of adaptive immunity in the CNS and the retina, both in the
      context of protection from infection as well as cancer and autoimmunity, while
      focusing on immune responses that compromise health and lead to significant
      morbidity.

PMID- 22466661
TI  - Fate of phosphorus fractions in an adsorptive-filter subject to intra- and inter
      event runoff phenomena.
AB  - In-situ filtration of phosphorus (P) and particulate matter (PM) transported in
      runoff is increasingly implemented for urban source areas. While monitoring of
      filter response is commonly based on an event mean of total phosphorus (TP), this
      study examines the fate of specific P fractions through intra- and inter-event
      phenomena. This continuous filter monitoring program includes 15 wet weather
      loadings and the dry weather periods between these events. Aqueous P adsorption
      and PM-bound P (suspended, settleable and sediment) filtration phenomena are
      examined for runoff events from a landscaped carpark with biogenic loads in
      Gainesville (GNV), FL. Filter response is compared to a similar aluminum oxide Al
      Ox modified media filter subject to anthropogenic loads from an urban paved
      source area in Baton Rouge (BTR), LA. Results for the GNV filter indicate that
      while intra-event settleable, sediment and dissolved P fractions are controlled
      by the filter, the suspended P fraction remained relatively mobile compared to
      the other P fractions. P adsorption is primarily influenced by intra-event flow
      rates, contact times, runoff volume, pH and by the inter-event chemistry of
      runoff stored in the filter. P effluent partitioning is dominated by the
      suspended PM as a consequence of effective adsorption by the filter. Inter-event
      phenomena generate decreasing redox with commensurate increases in alkalinity,
      conductivity as well as dissolved P as a consequence of re-partitioning.
      Dissolved P fate suggests that filters should be designed and managed to remain
      aerobic between wet weather events. For effective separation of suspended P and
      PM fractions by passive filters with low driving head, sustainability of
      performance, including head loss {<3 kPa}, requires upstream volumetric
      attenuation.

PMID- 22466663
TI  - An analysis of the allocation of Yakima River water in terms of sustainability
      and economic efficiency.
AB  - Decades of agricultural growth has led to the over appropriation of Yakima water
      and the ecological integrity of the Basin has been compromised. We evaluate the
      impact of current water allocation on the natural flow regime of the Yakima River
      using the Indicators of Hydrologic Alteration/Range of Variability Analysis and
      by quantifying indicators of ecosurplus and ecodeficit. We analyze the
      sustainability of the current water allocation scheme based on a range of
      sustainability criteria, from weak to strong to environmentally sustainable.
      Economic efficiency is assessed by describing the current allocation framework
      and suggesting ways to make it more efficient. Our IHA/RVA analysis suggests that
      the allocation of water in the Yakima River has resulted in a highly altered flow
      regime. Ecodeficit is far in excess of ecosurplus. We conclude that this
      allocation scheme is weakly sustainable, if sustainable at all, in its current
      framework. The allocation of water is also not economically efficient and we
      suggest that a reallocation of water rights may be necessary in order to achieve
      this objective. The creation of water markets to stimulate voluntary water rights
      transactions is the best way to approach economic efficiency. The first step
      would be to extend beneficial use requirements to include instream flows, which
      would essentially allow individuals to convert offstream rights into instream
      rights. The Washington trust water rights program was implemented as a means of
      creating a water market, which has contributed to the protection of instream
      flows, however more needs to be done to create an ideal water rights market so
      that rights migrate to higher valued uses, many of which are met instream.
      However, water markets will likely not solve the Yakima's water allocation
      problems alone; some degree of regulation may still be necessary.

PMID- 22466662
TI  - Contamination level and location of recreational freshwater influence the ability
      to predict Escherichia coli concentration by qPCR targeting Bacteroides.
AB  - Fecal bacteria are common microbial contaminants in freshwater with the potential
      to cause human illness. Detection of these microbes have traditionally relied on
      microbial plating to enumerate colonies of fecal indicator bacteria (FIB) such as
      Escherichia coli (E. coli), which can take 24 h or longer to complete.
      Quantitative PCR (qPCR) is a rapid and sensitive method for detection of FIB in
      recreational water that could compliment or potentially substitute for microbial
      plating. In this study, we have isolated DNA from the beach water on the
      shoreline at three different locations of Lake Erie and subjected these samples
      to qPCR to examine the relative abundance of Bacteroides. These values were
      compared to colony forming units (CFU) of E. coli. The resultant linear
      regressions between these different measurements of microbe concentration were
      used to determine the efficacy of qPCR targeting Bacteroides at predicting E.
      coli concentrations that are relevant for decision making by recreational water
      managers. Our findings indicate that the ability of Bacteroides to serve as an
      early predictive tool for E. coli CFU concentration depends on sample location
      and level of bacterial contamination, but can be used in some cases to supplement
      recreational water quality measurement and consequential management.

PMID- 22466660
TI  - Multiple sclerosis.
AB  - Multiple sclerosis (MS) is a multifocal demyelinating disease with progressive
      neurodegeneration caused by an autoimmune response to self-antigens in a
      genetically susceptible individual. While the formation and persistence of
      meningeal lymphoid follicles suggest persistence of antigens to drive the
      continuing inflammatory and humoral response, the identity of an antigen or
      infectious agent leading to the oligoclonal expansion of B and T cells is
      unknown. In this review we examine new paradigms for understanding the
      immunopathology of MS, present recent data defining the common genetic variants
      underlying disease susceptibility, and explore how improved understanding of
      immune pathway disruption can inform MS prognosis and treatment decisions.

PMID- 22466665
TI  - Bioluminescence imaging serves as a dynamic marker for guiding and assessing
      thermal treatment of cancer in a preclinical model.
AB  - BACKGROUND: Bioluminescence has been harnessed as a dynamic imaging technique in
      research. This is a proof of principle study examining feasibility of using
      bioluminescent proteins as a marker to guide therapeutic ablation. METHODS:
      Mesothelioma cancer cells (MSTO-Td) were transfected with a retroviral vector
      bearing firefly luciferase gene, plated in serial dilutions, and imaged to
      compare bioluminescence signal to cell number, determining threshold of
      bioluminescence detection. MSTO-Td cells were subjected to thermal treatment in a
      heated chamber; the bioluminescence signal and number of remaining live cancer
      cells were determined. Mice with MSTO-Td xenografts underwent electrocautery
      tumor ablation guided by bioluminescence imaging; bioluminescence signal and
      tumor size were monitored for 3 weeks. RESULTS: MSTO-Td cells emitted a bright,
      clear, bioluminescence signal that amplified with the cell number (P < .001) and
      was detectable with as few as 10 cells in cell culture. Bioluminescence decreased
      in a dose-dependent fashion upon thermal treatment as temperature increased from
      37 to 70  degrees C (P < .001) and as treatment duration increased from 5 to 20
      min (P < .001). This correlated with the number of remaining live MSTO-Td cells
      (Pearson coefficient = 0.865; P < .001). In mice, the bioluminescence signal
      correlated with tumor size posttreatment and effectively guided the ablation
      procedure to completion, achieving 0 % tumor recurrence. CONCLUSIONS:
      Bioluminescence imaging is a sensitive, real-time imaging approach;
      bioluminescence reporters such as firefly luciferase can assess and guide thermal
      treatment of cancer. This encourages research into bioluminescence imaging as a
      molecular technique with potential to target tumors via biomarkers and optimize
      thermal treatment procedures in a clinical setting.

PMID- 22466664
TI  - Radiation-associated angiosarcoma after breast cancer: high recurrence rate and
      poor survival despite surgical treatment with R0 resection.
AB  - BACKGROUND: Secondary angiosarcoma of the breast is a rare but severe long-term
      complication of breast cancer treated with breast-conserving surgery and
      radiotherapy. We characterized a population-based cohort of patients with
      secondary angiosarcomas from two tertiary hospitals to investigate this
      complication with respect to surgical treatment and outcome. METHODS: We
      identified 35 patients with a history of radiation for breast cancer that
      developed angiosarcoma in the irradiated field from 1990 to 2009. Of these, 31
      underwent surgery and were included for analysis. RESULTS: Angiosarcoma developed
      after median 7 years (range 3-25 years). R0 resection was obtained in 23 of 31
      patients after primary treatment. Local recurrence developed in 19 patients after
      median 6 months (range 1-89 months). Regional and distant metastases occurred in
      13 patients after median 17 months (range 2-50 months); nine which also had local
      recurrence. Patients whose local recurrence could be operated on had a better
      survival after treatment than those who were not considered for surgical
      treatment, median 34 months (range 6-84 months) compared with 6 months (range 5
      24 months). The median disease-free survival and disease-specific survival was 16
      and 37 months, respectively. CONCLUSIONS: Despite R0 resection, two-thirds of the
      patients developed a local recurrence. Survival among those with local recurrence
      was better if the patient could be treated with surgery. Overall, the prognosis
      was dismal and median DSS was just over 3 years.

PMID- 22466666
TI  - Pilot feasibility study of neoadjuvant chemoradiotherapy with S-1 in patients
      with locally advanced gastric cancer featuring adjacent tissue invasion or JGCA
      bulky N2 lymph node metastases.
AB  - BACKGROUND: To improve the prognosis of locally advanced gastric cancer, clinical
      trials of neoadjuvant chemotherapy (NAC) are being performed. Although
      neoadjuvant chemoradiotherapy (NACRT) generally achieves superior local tumor
      control to NAC, its efficacy for locally advanced gastric cancers remains
      unclear. Therefore, a prospective trial was conducted to explore the feasibility
      and safety of NACRT with oral S-1 in a series of cases. METHODS: Patients who had
      Japanese Gastric Cancer Association (JGCA) cStage IIIB gastric cancer were
      enrolled onto this study and received oral S-1 (65 mg/m(2)/day) administration
      and 50-Gy radiotherapy followed by radical surgery. The primary end points were
      completion of therapy and safety. RESULTS: Between October 2005 and September
      2008, 12 eligible patients were enrolled. Two could not complete the chemotherapy
      because of grade 3 toxicity. R0 resections were performed in 11 patients (91.7 %)
      (95 % confidence interval 61.5-99.8). Although operative morbidity was observed
      in two cases, there were no postoperative deaths. A pathologic response was
      observed in 10 patients (83.3 %). In five (62.5 %) of eight gastric cancers with
      invasion to adjacent structures, microscopic tumor deposits were not found in the
      affected organs. The 3-year survival rate was 58.3 % during a median follow-up
      period of 36 months. CONCLUSIONS: Although this study is preliminary, the present
      regimen seems to be feasible and safe as a treatment for locally advanced gastric
      cancers featuring adjacent tissue invasion or JGCA bulky N2 disease. This
      treatment approach should now be tested using the new tumor, node, metastasis
      staging system in a large clinical trial.

PMID- 22466667
TI  - Prognostic significance of antithrombin III levels for outcomes in patients with
      hepatocellular carcinoma after curative hepatectomy.
AB  - BACKGROUND: Although several studies have shown that serum antithrombin III
      (ATIII) has anti-inflammatory effects, the prognostic value of ATIII in HCC is
      unknown. We investigated the influence of preoperative ATIII levels on the
      outcome of patients who underwent hepatectomy for hepatocellular carcinoma (HCC).
      METHODS: Data from 440 patients (314 patients with ATIII >= 70 % and 126 patients
      with ATIII <70 %) who underwent curative hepatectomy for HCC were retrospectively
      collected and analyzed. To overcome bias due to the different distribution of
      covariates for the 2 groups, propensity score matching was performed on the
      patients, and outcomes were compared. RESULTS: The propensity score analysis
      revealed that 65 patients with ATIII of >= 70 % (group 1) and 65 patients with
      ATIII of <70 % (group 2) had the same preoperative and operative characteristics
      (excluding the ATIII level). The overall survival rate and the disease-free
      survival rate was significantly higher in group 1 than in group 2 (P = 0.005 and
      0.011, respectively). Multivariate analysis showed that ATIII was a significant
      favorable factor for overall survival and disease-free survival of patients with
      HCC after curative hepatectomy. CONCLUSIONS: The prognosis of patients with HCC
      was found to be associated with preoperative antithrombin III levels. ATIII may
      be useful for predicting outcomes of patients with HCC after curative
      hepatectomy.

PMID- 22466670
TI  - Vitamins at physiological levels cause oxidation to the DNA nucleoside
      deoxyguanosine and to DNA--alone or in synergism with metals.
AB  - Vitamins with antioxidant properties have the ability to act as pro-oxidants,
      inducing oxidative damage and oxidative stress as opposed to preventing it. While
      vitamin supplements are commonly consumed, the scientific evidence for their
      health beneficial effects is inconclusive. In fact, even harmful effects have
      been reported. The present study aimed to investigate and compare pro-oxidant
      properties of different antioxidants and vitamins commonly found in dietary
      supplements, at concentrations of physiological relevance, alone or in
      combination with metals also found in supplements. Focus was on damages related
      to DNA. The vitamins' chemical oxidation potencies were studied by measuring the
      amount of the oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)
      formed from the DNA nucleoside deoxyguanosine (dG) after vitamin exposure, using
      a high-performance liquid chromatography system with electrochemical and
      ultraviolet detection. To study the vitamins' ability to cause DNA damage to
      cultured cells, promyelocytic leukemia cells (HL-60) were exposed to vitamins,
      and strand breaks, alkali-labile sites and oxidative DNA lesions, i.e. formamido
      pyrimidine DNA glycosylase-sensitive sites, were detected using the comet assay.
      Vitamins A and C chemically induced oxidation of dG, alone and in synergism with
      iron or copper, whereas only vitamin C and copper induced DNA damage in cultured
      cells. Contrary, vitamins B1, B2, B3, B6 and B12, beta-carotene, folic acid,
      alpha-tocopherol, delta-tocopherol or gamma-tocopherol did not induce oxidative
      damage to dG, while lycopene induced a weak dose-response increase. Taken
      together, vitamin C and copper stood out with the strongest oxidative potency,
      which is of potential concern since both substances are commonly found in
      multivitamins.

PMID- 22466669
TI  - The development and fate of follicular helper T cells defined by an  IL-21
      reporter mouse.
AB  - Germinal centers require CD4+ follicular helper T cells (TFH cells), whose
      hallmark is expression of the transcriptional repressor Bcl-6, the chemokine
      receptor CXCR5 and interleukin 21 (IL-21). To track the development and fate of
      TFH cells, we generated an IL-21 reporter mouse by introducing sequence encoding
      green fluorescent protein (GFP) into the Il21 locus; these mice had expression of
      IL-21-GFP in CD4+CXCR5+PD-1+ TFH cells. IL-21-GFP+ TFH cells were multifunctional
      helper cells that coexpressed several cytokines, including interferon-g (IFN-g),
      IL-2 and IL-4. TFH cells proliferated and gave rise to transferrable memory cells
      with plasticity, which differentiated after recall into conventional effector
      helper T cells and TFH cells. Thus, we demonstrated that TFH cells were not
      terminally differentiated but instead retained the flexibility to be recruited
      into other helper T cell subsets and nonlymphoid tissues.

PMID- 22466668
TI  - Transcriptional profiling of stroma from inflamed and resting lymph nodes defines
      immunological hallmarks.
AB  - Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance,
      yet key aspects of their biology remain poorly elucidated. Here, comparative
      transcriptomic analyses of mouse LNSC subsets demonstrated the expression of
      important immune mediators, growth factors and previously unknown structural
      components. Pairwise analyses of ligands and cognate receptors across
      hematopoietic and stromal subsets suggested a complex web of crosstalk.
      Fibroblastic reticular cells (FRCs) showed enrichment for higher expression of
      genes relevant to cytokine signaling, relative to their expression in skin and
      thymic fibroblasts. LNSCs from inflamed lymph nodes upregulated expression of
      genes encoding chemokines and molecules involved in the acute-phase response and
      the antigen-processing and antigen-presentation machinery. Poorly studied
      podoplanin (gp38)-negative CD31(-) LNSCs showed similarities to FRCs but lacked
      expression of interleukin 7 (IL-7) and were identified as myofibroblastic
      pericytes that expressed integrin alpha(7). Together our data comprehensively
      describe the transcriptional characteristics of LNSC subsets.

PMID- 22466671
TI  - Human chorionic villus mesenchymal stromal cells reveal strong endothelial
      conversion properties.
AB  - Chorion, amnion and villi are reservoirs of mesenchymal stromal cells (StC) and
      the hypothesis that StC from fetal tissues retain higher plasticity compared to
      adult StC has been suggested. Aimed at investigating this aspect, a series of in
      vitro experiments were performed with StC isolated from first trimester human
      chorionic villi (CVStC). CVStC were cultured in: (i) standard mesenchymal medium
      (MM) and (ii) AmniomaxII(r) (AM), specifically designed to grow amnion-derived
      cells in prenatal diagnostic procedures. Cells were then exposed to distinct
      differentiation treatments and distinguished according to morphology,
      immunophenotype and molecular markers. Human StC obtained from adult bone marrow
      (BMStC) were used as control. CVStC cultured either in MM or AM presented stromal
      morphology and immunophenotype, were negative for pluripotency factors (Nanog,
      Oct-4 and Sox-2), lacked detectable telomerase activity and retained high genomic
      stability. In AM, however, CVStC exhibited a faster proliferation rate compared
      to BMStC or CVStC kept in MM. During differentiation, CVStC were less efficient
      than BMStC in acquiring adipocytes and osteocytes features; the cardiomyogenic
      conversion occurred at low efficiency in both cell types. Remarkably, in the
      presence of pro-angiogenic factors, CVStC reprogrammed toward an endothelial-like
      phenotype at significantly higher efficiency than BMStC. This effect was
      particularly evident in CVStC expanded in AM. Mechanistically, the reduced CVStC
      expression of anti-angiogenic microRNA could support this process. The present
      study demonstrates that, despite of fetal origin, CVStC exhibit restricted
      plasticity, distinct from that of BMStC and predominantly directed toward the
      endothelial lineage.

PMID- 22466673
TI  - Moral theories in medicine and psychiatry.

PMID- 22466674
TI  - Compulsory hospitalisation and optimal mental health care: A European perspective
      and the example of Greece.
AB  - Countries offering good psychiatric care which respects their clients' dignity
      and human rights can be expected to reflect this fact in their official health
      statistics. Given that European data on compulsory hospitalisation are currently
      inadequate, we propose that all Member States should collect at least a basic set
      of figures for calculating the rates or quotas of compulsory admissions and the
      rate of legally indefensible detentions; this will allow us to examine both the
      actual cost of freedom lost as well as the extent to which national mental health
      laws are delivered as prescribed. As shown here by the example of Greece, there
      is an urgent need to focus on possible infringements on the rights of the
      mentally ill, because Member States can nomicront be compelled to accept
      international monitoring or to observe minimum standards of mental health care.

PMID- 22466675
TI  - Drug-induced tardive motor syndromes.
AB  - Drug-induced tardive motor syndromes (TMS) is a group of disorders, characterized
      by involuntary movements of the tongue, face, lips, trunk and extremities,
      occurring after long-term exposure to a variety of pharmacological agents, mostly
      neuroleptics. The diagnosis of TMS requires exposure to dopamine receptor
      blocking agents for a period at least of 3 months, although for people over 60
      years old the necessary exposure period is limited to 1 month. The exact
      pathophysiology still remains obscure. The aim of this article is to review the
      phenomenology, epidemiology and treatment options of the TMS, as clinically
      distinct movement disorders. TMS include tardive dyskinesia, which is the most
      common movement disorder, tardive dystonia, tardive akathisia, tardive
      Tourettism, tardive tremor and tardive myoclonus as well as some specific
      syndromes less often presented such as Pisa, Meige and Rabbit syndromes.
      Prevention remains the cornerstone in good clinical practice. Preventive approach
      requires thorough diagnostic process with frequent reviews in order to determine
      the necessity of use and dosing of neuroleptic treatment. Clinical vigilance for
      early detection of signs of TMS as well as recording of early extrapyramidal side
      effects in the patient's history is needed, as these may predict the occurrence
      of TMS. In case of occurrence of TMS, gradual discontinuation of the offending
      agent is required. Therapeutic interventions include the administration of the
      following agents: atypical antipsychotics (mainly clozapine), benzodiazepines,
      vitamin E, reserpine, tetrabenazine, anticholinergics, botulinum toxin A. The
      early management of TMS is crucial for the patients' better clinical outcome and
      improved quality of life.

PMID- 22466672
TI  - Immune aging and autoimmunity.
AB  - Age is an important risk for autoimmunity, and many autoimmune diseases
      preferentially occur in the second half of adulthood when immune competence has
      declined and thymic T cell generation has ceased. Many tolerance checkpoints have
      to fail for an autoimmune disease to develop, and several of those are
      susceptible to the immune aging process. Homeostatic T cell proliferation which
      is mainly responsible for T cell replenishment during adulthood can lead to the
      selection of T cells with increased affinity to self- or neoantigens and enhanced
      growth and survival properties. These cells can acquire a memory-like phenotype,
      in particular under lymphopenic conditions. Accumulation of end-differentiated
      effector T cells, either specific for self-antigen or for latent viruses, have a
      low activation threshold due to the expression of signaling and regulatory
      molecules and generate an inflammatory environment with their ability to be
      cytotoxic and to produce excessive amounts of cytokines and thereby inducing or
      amplifying autoimmune responses.

PMID- 22466676
TI  - Addiction, culture and family therapy strategies.
AB  - Tauhis update reviews the empirical evidence supporting the use of couple and
      family therapies in managing families affected by addiction, both adolescent and
      adult populations. A particular focus of the paper is the need for a "culturally
      competent" strategy in assessing and treating target families.

PMID- 22466677
TI  - On the concept of vulnerability, identity and nostalgia affecting the
      immigrational experience.
AB  - Tauhis paper focuses on the vicissitudes affecting the immigrational experience
      of Greeks in the United States. It is based on observations and insights
      emanating from psychotherapeutic work with Greek immigrants at the Transcultural
      Center of Human Relations in Chicago. These immigrants presented with specific
      symptomatologies including anxiety, depression, psychophysiologic manifestations
      and gross stress reactions sometimes culminating in transient psychotic episodes
      necessitating brief psychiatric hospitalization. This study proposes to elucidate
      the dynamic factors leading to specific psychopathologies observed including the
      feeling of increased vulnerability and helplessness felt by the immigrant in the
      new cultural environment in the host country along with feelings if alienation,
      the shattering of the sense of identity and the ensuing nostalgia motivating the
      quest to return to the homeland. The study also describes the treatment
      approaches including the psychotherapeutic interactions required to bring about
      significant operational changes to provide symptomatologic relief and
      stabilization towards an improved adaptation to the current life's circumstances.
      The presented three ongoing cases in point dramatically portray the intensity and
      complexity of the actual experiences of these immigrants and their response to
      the applicable therapeutic modalities.

PMID- 22466678
TI  - Challenging behaviours on people with autism: A case study on the effect of a
      residential training programme based on structured teaching and TEACCH method.
AB  - The purpose of the study is the investigation of how effective could be one of
      the first residential training programmes based on structured teaching and the
      principles of TEACCH method, in declining the frequency of challenging behaviours
      in adolescents and adults with autism, who had never received any kind of
      intervention or training. Functional assessment records (ABC) were analysed for
      each participant and frequencies of challenging behaviours were summarised for
      three deferent periods of time (beginning of the programme, after 12 and 18
      months). The results showed significant decline of challenging behaviours
      frequency after the start of the training programme. The implications of the
      results in particular will be valuable for further research and service
      developments in Greece by the Greek Society for the Protection of Autistic
      People.

PMID- 22466679
TI  - "Hysteria" near the end of the twentieth century in Athens.
AB  - The aim of this study was to study the frequencies of clinical manifestations
      traditionally associated with the concept of "hysteria", namely conversion,
      dissociation, and somatization in the emergency room of the Department of
      Psychiatry in Athens in the late 1990s, in a period of significant social change
      of the Greek culture towards more Western standards. We used a retrospective
      chart review of all new emergency room cases in a representative two-year period
      (1995-1997), replicating the method and the diagnostic classification of a study
      from our Department published 25 years ago, investigating similar changes in
      these symptoms in previous periods of change in the Greek social structure. Of
      7424 new cases 215 (2.9%) fulfilled criteria for "hysteria", a significant
      reduction from the original study. Of these 28 were foreign, mostly from non
      Western cultural settings. Male to female ratio (1:3) and mean age remained
      unchanged from the original study. Hysterical fits (pseudoseizures) were
      significantly less in comparison to the original study. Mental and vegetative
      conversion (corresponding to dissociative and somatoform disorders, respectively)
      remained unchanged, mixed conversion increased while changes in somatic
      conversion (conversion disorder) depended on the nationality of the patients.
      Over the last quarter century in Athens rates of patients with so called
      "hysterical symptoms" continue to decrease, as do the most dramatic
      presentations. These reductions however, are not so great to suggest a
      disappearance of the syndrome, while increase of the mixed forms suggest that sub
      syndromes may have common underlying mechanisms. This may point towards a single
      disease process with multiple presentations rather than separate diagnostic
      categories. Culture appears to influence clinical expression of symptoms.

PMID- 22466680
TI  - Evaluation of therapy with clozapine in outpatient treatment-resistant
      schizophrenics in Cyprus.
AB  - Clozapine is an atypical antipsychotic formulation indicated for schizophrenic
      patients who are unresponsive or intolerant to traditional antipsychotic therapy.
      Treatment with this agent is prevalent among schizophrenic patients under
      psychiatric hospital care, but not among non-hospitalized patients. The aim of
      this study was to evaluate the response to clozapine treatment, and specifically
      the effects on the overall functioning of a group of out-patient treatment
      resistant schizophrenics. Data from 66 treatment-resistant schizophrenics in
      Cyprus, 28 female and 38 male, were retrospectively retrieved. The scales used
      for assessment were Global Assessment of Functioning Scale (GAF) and the Positive
      and Negative Syndrome Scale (PANSS). Also, white blood cell (WBC) counts were
      examined. Based on the GAF scale it was determined that there was a 49.7+/-23.6
      SD point (P < 0.001) significant improvement in the functioning of these patients
      at the end of the evaluation period with clozapine. Furthermore, utilizing the
      PANSS, it was concluded that treatment with clozapine significantly improved the
      positive and negative symptoms as well as the general psychopathology of this
      patient group. In total, 9 patients were taken off the medication because 2
      patients (3%) were completely cured, 5 patients (8%) were unresponsive, 2 (3%)
      were non-compliant, 1 (2%) developed diabetes and 1 (2%) had considerably low WBC
      counts during the treatment. The incidence of WBC reduction and need for
      discontinuation of therapy falls within the expected range of this abnormality in
      patients taking clozapine. WBC counts were performed weekly for the first 18
      weeks and monthly thereafter showed that there was no negative effect on the WBC
      counts of 65 out of the 66 patients, and thus indicate that clozapine can be
      safely administered at an out-patient basis. The data indicate a strong
      improvement in the functioning of this group of patients under outpatient
      clozapine treatment, without compromising patient safety.

PMID- 22466681
TI  - NIR emitting ytterbium chelates for colourless luminescent solar concentrators.
AB  - A new oxyiminopyrazole-based ytterbium chelate enables NIR emission upon UV
      excitation in colorless single layer luminescent solar concentrators for building
      integrated photovoltaics.

PMID- 22466682
TI  - Social media, digital video and health promotion in a culturally and
      linguistically diverse Australia.
AB  - Participatory processes are effective for digital video production that promotes
      health and wellbeing with communities from diverse cultural and linguistic
      backgrounds, including migrants and refugees. Social media platforms YouTube,
      Vimeo, Flickr and others demonstrate potential for extending and enhancing this
      production approach. However, differences within and between communities in terms
      of their quality of participation online suggest that social media risk becoming
      exclusive online environments and a barrier to health and wellbeing promotion.
      This article examines the literature and recent research and practice in
      Australia to identify opportunities and challenges when using social media with
      communities from diverse cultural and linguistic backgrounds. It proposes a
      hybrid approach for digital video production that integrates 'online' and
      'offline' participation and engages with the differences between migrants and
      refugees to support more inclusive health and wellbeing promotion using digital
      technology. 

PMID- 22466683
TI  - An order-N electronic structure theory with generalized eigenvalue equations and
      its application to a ten-million-atom system.
AB  - A linear algebraic theory called the 'multiple Arnoldi method' is presented and
      realizes large-scale (order-N) electronic structure calculations with generalized
      eigenvalue equations. A set of linear equations, in the form of (zS - H)x = b,
      are solved simultaneously with multiple Krylov subspaces. The method is
      implemented in a simulation package ELSES (www.elses.jp) with tight-binding-form
      Hamiltonians. A finite-temperature molecular dynamics simulation is carried out
      for metallic and insulating materials. A calculation with 10(7) atoms was
      realized by a workstation. The parallel efficiency is shown up to 1024 CPU cores.

PMID- 22466684
TI  - Laparoscopic hernioraphy: a better approach for recurrent hernia in boys?
AB  - PURPOSE: We aimed to compare laparoscopic hernia repair and open hernia repair in
      recurrent cases after first open repair according to the length of time taken to
      perform the procedure. METHODS: Between November 2009 and December 2011, the
      medical records of 26 male paediatric patients who were treated with laparoscopic
      surgery (with Schier's intracorporal "N" suture closure) and open surgery (with
      high ligation technique) in our institution for recurrent inguinal hernia were
      reviewed for the length of the operative time and post-operative complications
      retrospectively. Thirteen cases operated with laparoscopic repair were regarded
      as Group 1 and other 13 cases operated with the open high ligation repair were
      regarded as Group 2. All recurrent hernia cases had been performed in other
      hospitals with the open high ligation technique previously. RESULTS: Thirteen
      internal inguinal ring closures in Group 1 were performed laparoscopically. In
      Group 2, 13 cases underwent open high ligation repair. Comparing the laparoscopic
      and open-repair techniques in the recurrent cases (Group 1 vs. Group 2; 32.36 vs.
      61.07 min, respectively) showed that the length of the operation time was much
      shorter in laparoscopic repair group (Group 1) than open repair group (Group 2).
      A statistically significant difference was also observed (p = 0.001). No post
      operative testicular atrophy or recurrence was seen until present time in all
      groups. CONCLUSION: We propose that laparoscopic repair in recurrent childhood
      inguinal hernia cases, developed after open repair, avoids entering a fibrotic
      inguinal canal, making the procedure easier and shorter. Laparoscopic
      herniorrhaphy is a good alternative option in recurrent childhood hernia.

PMID- 22466685
TI  - Factors associated with parent report of access to care and the quality of care
      received by children 4 to 17 years of age in Georgia.
AB  - We examined factors associated with health care access and quality, among
      children in Georgia. Data from the 2007 National Survey of Children's Health were
      merged with the 2008 Area Resource File. The medically underserved area variable
      was appended to the merged file, restricting to Georgia children ages 4-17 years
      (N = 1,397). Study outcomes were past-year access to care, defined as utilization
      of preventive medical care and no occasion of delay or denial of needed care; and
      quality of care received, defined as compassionate, culturally-effective, and
      family-centered care which was categorized as higher, moderate, or lower.
      Analysis included binary and multinomial logit modeling. In our study population,
      80.8 % were reported to have access to care. The quality of care distribution
      was: higher (39.4 %), moderate (30.6 %), and lower (30.0 %). Younger age (4-9
      years) was positively associated with having access to care. Compared to children
      who had continuous and adequate private insurance, children who were
      never/intermittently insured or who had continuous and inadequate private
      insurance were less likely to have access. Compared to children who had
      continuous and adequate private insurance, there were lower odds of perceiving
      received care as higher/moderate versus lower quality among children who were
      never/intermittently insured or who had continuous and inadequate/adequate public
      insurance. Being in excellent/very good health and living in safe/supportive
      neighborhoods were positively associated with quality; non-white race/ethnicity
      and federal poverty level were negatively associated with quality. Assuring
      continuous, adequate insurance may positively impact health care access and
      quality.

PMID- 22466686
TI  - Medical home access among American Indian and Alaska Native children in 7 states:
      National Survey of Children's Health.
AB  - To describe the prevalence of medical home among American Indian and Alaska
      Native children (AIAN) compared to non-Hispanic white (NHW) children and identify
      areas for improvement in the provision of care within a medical home. Prevalence
      of medical home, defined as family-centered, comprehensive, coordinated,
      compassionate, culturally effective care, including a personal doctor or nurse
      and usual care location, was estimated using 2007 National Survey of Children's
      Health data. Analyses included 1-17 year-olds in states reporting AIAN race as a
      distinct category (Alaska, Arizona, Montana, New Mexico, North Dakota, Oklahoma,
      and South Dakota, n = 9,764). Associations between medical home and demographic
      (child's age, household education and income, and state) and health-related
      [child's insurance status, special health care need status, and past year Indian
      Health Service (IHS) utilization] characteristics were assessed among AIAN
      children. Overall, the prevalence of medical home was 27 % lower among AIAN
      children (42.6, 95 % CI = 34.4-50.8) than NHW children (58.3, 95 % CI = 56.2
      60.4). Child's age (adjusted OR [aOR] = 2.7, 95 % CI = 1.3-5.6) was significantly
      associated with medical home. IHS utilization was associated with medical home
      among AIAN children with private insurance (aOR = 0.2, 95 % CI = 0.1-0.4), but
      not among uninsured or publicly insured children. Care coordination and family
      centered care were noted areas for improvement among AIAN children. Less than
      half of AIAN children had a medical home. Future studies should further examine
      the intersection between insurance and IHS to determine if enhanced coordination
      is needed for this population, which is often served by multiple federally-funded
      health-related programs.

PMID- 22466687
TI  - Axonal transport deficit in a KIF5A( -/- ) mouse model.
AB  - Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder
      preferentially affecting the longest corticospinal axons. More than 40 HSP
      genetic loci have been identified, among them SPG10, an autosomal dominant HSP
      caused by point mutations in the neuronal kinesin heavy chain protein KIF5A.
      Constitutive KIF5A knockout (KIF5A( -/- )) mice die early after birth. In these
      mice, lungs were unexpanded, and cell bodies of lower motor neurons in the spinal
      cord swollen, but the pathomechanism remained unclear. To gain insights into the
      pathophysiology, we characterized survival, outgrowth, and function in primary
      motor and sensory neuron cultures from KIF5A( -/- ) mice. Absence of KIF5A
      reduced survival in motor neurons, but not in sensory neurons. Outgrowth of axons
      and dendrites was remarkably diminished in KIF5A( -/- ) motor neurons. The number
      of axonal branches was reduced, whereas the number of dendrites was not altered.
      In KIF5A( -/- ) sensory neurons, neurite outgrowth was decreased but the number
      of neurites remained unchanged. In motor neurons maximum and average velocity of
      mitochondrial transport was reduced both in anterograde and retrograde direction.
      Our results point out a role of KIF5A in process outgrowth and axonal transport
      of mitochondria, affecting motor neurons more severely than sensory neurons. This
      gives pathophysiological insights into KIF5A associated HSP, and matches the
      clinical findings of predominant degeneration of the longest axons of the
      corticospinal tract.

PMID- 22466688
TI  - Microglia in the cerebral cortex in autism.
AB  - We immunocytochemically identified microglia in fronto-insular (FI) and visual
      cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched
      controls, and stereologically quantified the microglial densities. Densities were
      determined blind to phenotype using an optical fractionator probe. In FI,
      individuals with autism had significantly more microglia compared to controls (p
      = 0.02). One such subject had a microglial density in FI within the control range
      and was also an outlier behaviorally with respect to other subjects with autism.
      In VC, microglial densities were also significantly greater in individuals with
      autism versus controls (p = 0.0002). Since we observed increased densities of
      microglia in two functionally and anatomically disparate cortical areas, we
      suggest that these immune cells are probably denser throughout cerebral cortex in
      brains of people with autism.

PMID- 22466689
TI  - Rating parent-child interactions: joint engagement, communication dynamics, and
      shared topics in autism, Down syndrome, and typical development.
AB  - A battery of 17 rating items were applied to video records of typically
      developing toddlers and young children with autism and Down syndrome interacting
      with their parents during the Communication Play Protocol. This battery provided
      a reliable and broad view of the joint engagement triad of child, partner, and
      shared topic. Ratings of the child's joint engagement correlated very strongly
      with state coding of joint engagement and replicated the finding that coordinated
      joint engagement was less likely in children with autism. Ratings of other child
      actions, of parent contributions, and of shared topics and communicative dynamics
      also documented pervasive variations related to diagnosis, language facility, and
      communicative context.

PMID- 22466690
TI  - Developing a vocational index for adults with autism spectrum disorders.
AB  - Existing methods of indexing the vocational activities of adults with autism
      spectrum disorders (ASD) have made significant contributions to research.
      Nonetheless, they are limited by problems with sensitivity and reliability. We
      developed an index of vocational and educational outcomes that captures the full
      range of activities experienced by adults with ASD, and that can be reliably
      coded across studies using specific decision rules. To develop this index, we
      used employment, vocational, and educational data collected from nearly 350
      adults with ASD at 6 times over 12 years, as part of a larger longitudinal study.
      The resulting index consists of 11 categories coded on a 9-point scale, ranging
      from competitive employment and/or postsecondary educational program to no
      vocational/educational activities.

PMID- 22466691
TI  - Primary pulmonary artery sarcoma presenting as right heart failure.

PMID- 22466692
TI  - Transcatheter aortic valve and aortic homograft reintervention.

PMID- 22466693
TI  - Massive pulmonary embolism: surgical embolectomy versus thrombolytic therapy-
      should surgical indications be revisited?
AB  - OBJECTIVES: The treatment of massive pulmonary embolism (PE) is a matter of
      debate. We present our institutional experience of patients suffering from
      massive PE with the aim of comparing the early results, the outcome and quality
      of life (QoL) between patients primarily assigned to either pulmonary surgical
      embolectomy (SE) or thrombolytic therapy (TL). A subgroup of patients (TS) with
      failed responses to TL requiring SE was separately analysed. METHODS: All
      consecutive patients (January 2001-December 2007) with computed tomography (CT)
      scan-confirmed massive bilateral central or paracentral PE were reviewed. All
      clinical data were retrieved from our patients' registry and completed by the
      evaluation of the CT-scan-derived right ventricle/left ventricle ratio (RV/LV
      ratio). Follow-up focused on clinical outcome and QoL was obtained. RESULTS:
      Eighty patients were analysed including 28 SE (35%) and 52 TL (65%), of whom 11
      (21%) required TS. Demographics and preoperative characteristics were similar
      between SE and TL. Analysis of the RV/LV ratio revealed a ratio of 1.66 for SE
      and 1.44 for TL. The early mortality rate was not significantly different between
      the two groups (SE: 3.6% versus TL: 13.5%), whereas early mortality was 27% in
      those patients treated initially with thrombolysis and subsequently requiring SE
      (TS-group). Severe bleeding complications were lower in the SE-group (3.6% versus
      26.5% P = 0.013). Intracerebral bleeding rates and neurological events were not
      statistically different. After a mean follow-up of 63 +/- 21 months, the
      mortality rate was 17.9% in the SE-group and 23.1% in the TL-group. CONCLUSIONS:
      SE is an excellent treatment option in massive PE with comparable early mortality
      rates and significantly less bleeding complications than TL. Patients having
      surgery after inefficient thrombolysis have the worst early outcome. The RV/LV CT
      scan ratio might serve as a predictor to differentiate patients, who could profit
      from direct surgical intervention than thrombolytic treatment attempts. Further
      studies are required to confirm these results.

PMID- 22466694
TI  - Pre-treatment maximal oesophageal wall thickness is independently associated with
      response to chemoradiotherapy in patients with T3-4 oesophageal squamous cell
      carcinoma.
AB  - OBJECTIVES: Combined chemoradiotherapy with or without surgery is frequently
      performed as a curative treatment in patients with T3-4 locally advanced
      oesophageal squamous cell carcinoma. Computed tomography (CT) is frequently
      performed before and after chemoradiotherapy. The aim of this study is to
      evaluate the utility of the oesophageal wall thickness on CT scans to predict the
      response to chemoradiotherapy and the treatment outcome in patients with T3-4
      locally advanced oesophageal squamous cell carcinoma. METHODS: Ninety-six
      patients with T3-4 locally advanced oesophageal squamous cell carcinoma, who were
      treated with neoadjuvant chemoradiotherapy followed by surgery between 1998 and
      2008 at the Kaohsiung Chang Gung Memorial Hospital, were retrospectively
      reviewed. CT scans before and after chemoradiotherapy were available for 93
      patients. Of these 93 patients, 24% (22 of 93) achieved a pathologically complete
      response (pCR). The measurement of the maximal dimension of the oesophageal wall
      thickness on CT scans before (pre) and after (post) chemoradiotherapy was
      performed retrospectively, and correlated with the response to chemoradiotherapy
      and patients' outcome. The percentage decrease of maximal oesophageal wall
      thickness after chemoradiotherapy was determined by the formula: [(pre 
      post)/pre] 100. RESULTS: Pre- and post-chemoradiotherapy maximal oesophageal wall
      thicknesses were significantly correlated with pCR, but the percent decrease of
      oesophageal wall thickness after chemoradiothrapy was not. Logistic models showed
      that pre-chemoradiotherapy maximal oesophageal wall thickness >=20 mm was
      independently associated with response to chemoradiotherapy. For patients with
      pre-chemoradiotherapy maximal oesophageal wall thickness >=20 mm, 91% did not
      achieve pCR after chemoradiotherapy. Univariate analyses demonstrated that a pre
      chemoradiotherapy maximal oesophageal wall thickness >=20 mm, T4 disease and
      positive regional lymph nodes (N stage) were predictive of inferior disease-free
      survival. In a multivariate comparison, pre-chemoradiotherapy maximal oesophageal
      wall thickness >=20 mm represented an independent adverse prognosticator for
      disease-specific survival and disease-free survival. CONCLUSIONS: Most of the T3
      4 locally advanced oesophageal squamous cell carcinoma patients with pre
      treatment maximal oesophageal wall thickness >=20 mm did not achieve pCR after
      chemoradiotherapy. Thus, oesophgectomy may be considered in advance in this group
      of patients. Pre-treatment maximal oesophageal wall thickness is of independent
      prognostic value in patients with T3-4 locally advanced oesophageal squamous cell
      carcinoma who receive neoadjuvant chemotheradiotherapy.

PMID- 22466695
TI  - Curative replacement of the dissected aortic arch: a new insight to resolve an
      old question 'how extended should the arch repair be?'.

PMID- 22466696
TI  - Massive haemoptysis on veno-arterial extracorporeal membrane oxygenation.
AB  - A 49-year old female presented with severe heart failure with end-organ
      dysfunction and was placed on veno-arterial extracorporeal membrane oxygenation
      (ECMO) as a bridge to a decision for end-organ recovery. While on ECMO, the
      patient developed massive haemoptysis after a Swan-Ganz catheter manipulation.
      The haemoptysis was not controllable by conventional methods including
      bronchoscopy with cold saline and epinephrine lavage, bronchial blocker or
      angiography. The endotracheal tube was clamped to provide tamponade and the
      patient relied on full ECMO support for 36 h. After the haemoptysis resolved, the
      endotracheal tube was unclamped. The patient developed adult respiratory distress
      syndrome and was ventilated using the ARDSnet protocol with continued support
      from ECMO. On post-ECMO day 20, the patient underwent a successful ECMO wean and
      a Heart Mate II left ventricular assist device placement.

PMID- 22466697
TI  - Leukocyte filtration of blood cardioplegia attenuates myocardial damage and
      inflammation.
AB  - OBJECTIVES: Leukocyte filtration of blood cardioplegia (cLkF) is postulated to
      reduce ischaemia-reperfusion myocardial injury. Contradictory results have been
      published and few studies have addressed perioperative cytokine leakage and
      haemodynamic status after LkF. METHODS: Thirty patients undergoing isolated
      aortic valve replacement were randomized to cLkF (cLkF-Group) or to standard cold
      blood cardioplegia (S-Group). Troponin I (TnI) and lactate were sampled from the
      coronary sinus at reperfusion. Peripheral TnI and lactate were collected
      preoperatively at admission, and in the intensive care unit (ICU) at 8, 12, 36
      and 60 h postoperatively. Cardiac index (CI), indexed systemic vascular
      resistances, cardiac cycle efficiency (CCE) and central venous pressure (CVP)
      were registered preoperatively, at admission to the ICU and at the 6th, 12th,
      18th, 24th and 36th postoperative hour. IL-6, IL-8, TNF-alpha and IL-10 were
      sampled preoperatively, at reperfusion, on admission to the ICU and the 6th, 18th
      and 24th postoperative hours. RESULTS: The cLkF group showed lower TnI (2.4 +/-
      0.4 vs. 5.1 +/- 0.8 MUg/l, P = 0.0001) and lactate (0.9 +/- 0.1 vs. 1.6 +/- 0.2
      mmol/l, P = 0.0001) from the coronary sinus at reperfusion. TnI levels (group-P =
      0.0001, group time-P < 0.0001) and lactate (group time-P = 0.001) remained lower
      postoperatively after cLkF. Ventricular defibrillation at aortic declamping was
      less common in the cLkF-Group (33.3% vs. S-Group: 93.3%; P = 0.002). Cytokines
      demonstrated significant postoperative leakage (time-P = 0.0001 in both groups
      for IL-6, IL-8, TNF-alpha, IL-10), with lower pro-inflammatory (IL-6 group-P =
      0.0001, group time-P = 0.0001; IL-8 group-P = 0.0001, group time-P = 0.007; TNF
      alpha group-P = 0.0001; group time-P = 0.012) and higher anti-inflammatory
      cytokine secretion after cLkF (IL-10 group-P = 0.005). Perioperative haemodynamic
      indices proved to be similar between the two groups (group-P = NS for CI, SVRI,
      CCE and CVP). CONCLUSIONS: cLkF during blood cardioplegia attenuates myocardial
      ischaemia/reperfusion injury and reduces perioperative leakage of TnI, lactate
      and pro-inflammatory cytokines. These data did not result in a better
      haemodynamic status.

PMID- 22466698
TI  - The fate of abstracts presented at annual meetings of the Society for
      Cardiothoracic Surgery in Great Britain and Ireland from 1993 to 2007.
AB  - Although the presentation of original research to learned societies is valuable,
      the target should be publication in a peer-reviewed journal. Therefore, the
      strength of a meeting may be assessed by the rate of the subsequent publication
      of papers from the presented abstracts. We conducted an analysis of abstracts
      presented at consecutive annual meetings of the Society for Cardiothoracic
      Surgery (SCTS) in Great Britain and Ireland over a 15-year period. Abstract books
      and other documentation from the 1993-2007 meetings were reviewed; abstracts from
      other major Cardiothoracic Surgery meetings held in 2007 were also reviewed.
      Medline was searched to identify the peer-reviewed publications arising from each
      work presented. For abstracts presented at SCTS in 2003-07, the factors
      potentially associated with publication were analysed by logistic regression. If
      no publications were identified, authors were contacted through a standardized
      email questionnaire to ascertain its status and reasons for non-publication. Over
      the 15-year period, 909 abstracts were presented at the SCTS meetings. The rate
      of publication rose from ~30% in the mid-1990s to consistently >60% from recent
      meetings, with a high of 81.3% from 2006. However, in comparison with other
      Cardiothoracic Surgery meetings in 2007, the chance of subsequent publication
      from SCTS (66.7%) was lower than from the European Association for Cardio
      Thoracic Surgery (75.0%), the American Association for Thoracic Surgery (83.9%)
      and The Society of Thoracic Surgeons (72.5%) meetings. For abstracts presented at
      the last five SCTS meetings, publication was most commonly in a speciality
      journal (56.3%) and the median time for publication was 15 months (range -24 to
      63 months) with 14 papers published prior to presentation at the meeting. On
      regression analysis, the only factor associated with publication was the study
      design comparing randomized trials and systematic reviews with other types of
      study (P < 0.01). Of the 90 unpublished abstracts, 48 (53.3%) authors replied to
      an email questionnaire revealing that 41 (85.4%) were never submitted for
      publication. The most common reasons given were low priority (29.6%) and low
      likelihood of acceptance (24.1%). In recent years, the annual meeting of the
      Society has become a forum for the presentation of high-quality research that
      usually withstands peer-review, most commonly in a speciality journal. The rate
      of publication has increased to consistently >60%, although those that remain
      unpublished are generally never submitted. This compares favourably with national
      meetings of other surgical societies, although it is lower than other major
      cardiothoracic meetings which have an affiliated journal. At a time when it has
      been suggested that medical research in the UK is in decline, cardiothoracic
      surgery appears to be thriving.

PMID- 22466699
TI  - Evaluation of stuck mechanical valve with four-dimensional computed tomography.

PMID- 22466700
TI  - Risk of late aortic events after an isolated aortic valve replacement for
      bicuspid aortic valve stenosis with concomitant ascending aortic dilation.
AB  - OBJECTIVES: The optimal surgical treatment of patients with bicuspid aortic valve
      (BAV) disease and ascending aortic aneurysm is controversial. The aim of this
      study was to evaluate the risk of late aortic events after an isolated aortic
      valve replacement (AVR) for BAV stenosis with concomitant mild-to-moderate
      proximal aortic dilation. METHODS: A review of our institutional BAV database
      identified a subgroup of 153 consecutive BAV patients (mean age 54.2 +/- 10.5
      years, 73% men) with BAV stenosis and concomitant ascending aortic dilation of 40
      50 mm who underwent an isolated AVR from 1995 to 2000. All cases of simultaneous
      aortic surgery (i.e. ascending aorta with a diameter of >50 mm) were excluded.
      The follow-up (1759 patient-years) was 100% complete. The mean follow-up was 11.5
      +/- 3.2 years. Adverse aortic events were defined as the need for proximal aortic
      surgery, the occurrence of aortic dissection/rupture or sudden death during the
      follow-up. RESULTS: Actuarial survival rates of our study population were 86 and
      78% at 10 and 15 years, respectively. Ascending aortic surgery was required in
      five patients (3%) for progressive ascending aortic aneurysm. Freedom from aortic
      interventions at 10 and 15 years was 97 and 94%, respectively. No documented
      aortic dissection or rupture occurred. Freedom from adverse aortic events was 95%
      at 10 years and 93% at 15 years postoperatively. In a separate group of patients
      presenting with aortic insufficiency (i.e. root phenotype), freedom from adverse
      aortic events was significantly lower (88 and 70% at 10 and 15 years, P = 0.009).
      CONCLUSIONS: BAV patients with aortic valve stenosis and concomitant mild-to
      moderate ascending aortic dilation are at a considerably low risk of adverse
      aortic events at 15 years after an isolated AVR. The BAV phenotype should be
      considered when determining the risk of subsequent adverse aortic events and the
      need for concomitant aortic replacement.

PMID- 22466702
TI  - 3D GRASE arterial spin labelling reveals an inverse correlation of cortical
      perfusion with the white matter lesion volume in MS.
AB  - BACKGROUND: We hypothesized that in multiple sclerosis (MS) patients, reduced
      cortical perfusion is associated with chronic white matter injury. OBJECTIVE: To
      investigate the influence of different clinical and magnetic resonance imaging
      characteristics on cortical perfusion. METHODS: Cerebral blood flow (CBF) was
      assessed by applying a pulsed arterial spin labelling (ASL) technique combined
      with single-shot 3D-GRASE (gradient-spin echo) in a cohort of 165 MS patients
      with a relapsing-remitting (n=123) or secondary progressive disease course
      (n=42). Mean age was 45.4 years (20-68 years), mean disease duration was 14.2
      years (1-48 years). RESULTS: Mean cortical CBF was 45.6 ml/100g per min (SD: 7.8
      ml/100g per min). Stepwise multiple linear regression models were calculated to
      investigate the relationship between different factor sets and mean CBF. The
      model with the highest adjusted coefficient of determination included T2 lesion
      load, age, gender and disease duration as significant factors. Post-hoc Spearman
      rank correlation revealed significant correlation of adjusted CBF with T2 lesion
      load (rho=-0.35, p=1*10(-6)), with age (rho=-0.34, p=4*10(-6)), and with disease
      duration (rho=0.16, p=0.03), while Expanded Disability Status Scale (EDSS) did
      not reach significance in either model. CONCLUSION: This study suggests that the
      amount of white matter lesions indicates a reduced metabolic demand and reduced
      perfusion at a cortical level.

PMID- 22466703
TI  - RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing.
AB  - Alternative splicing has a major role in cardiac adaptive responses, as
      exemplified by the isoform switch of the sarcomeric protein titin, which adjusts
      ventricular filling. By positional cloning using a previously characterized rat
      strain with altered titin mRNA splicing, we identified a loss-of-function
      mutation in the gene encoding RNA binding motif protein 20 (Rbm20) as the
      underlying cause of pathological titin isoform expression. The phenotype of Rbm20
      deficient rats resembled the pathology seen in individuals with dilated
      cardiomyopathy caused by RBM20 mutations. Deep sequencing of the human and rat
      cardiac transcriptome revealed an RBM20-dependent regulation of alternative
      splicing. In addition to titin (TTN), we identified a set of 30 genes with
      conserved splicing regulation between humans and rats. This network is enriched
      for genes that have previously been linked to cardiomyopathy, ion homeostasis and
      sarcomere biology. Our studies emphasize the key role of post-transcriptional
      regulation in cardiac function and provide mechanistic insights into the
      pathogenesis of human heart failure.

PMID- 22466704
TI  - Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in
      ataxia telangiectasia.
AB  - Ataxia telangiectasia is a neurodegenerative disease caused by mutation of the
      Atm gene. Here we report that ataxia telangiectasia mutated (ATM) deficiency
      causes nuclear accumulation of histone deacetylase 4 (HDAC4) in neurons and
      promotes neurodegeneration. Nuclear HDAC4 binds to chromatin, as well as to
      myocyte enhancer factor 2A (MEF2A) and cAMP-responsive element binding protein
      (CREB), leading to histone deacetylation and altered neuronal gene expression.
      Blocking either HDAC4 activity or its nuclear accumulation blunts these
      neurodegenerative changes and rescues several behavioral abnormalities of ATM
      deficient mice. Full rescue of the neurodegeneration, however, also requires the
      presence of HDAC4 in the cytoplasm, suggesting that the ataxia telangiectasia
      phenotype results both from a loss of cytoplasmic HDAC4 as well as its nuclear
      accumulation. To remain cytoplasmic, HDAC4 must be phosphorylated. The activity
      of the HDAC4 phosphatase, protein phosphatase 2A (PP2A), is downregulated by ATM
      mediated phosphorylation. In ATM deficiency, enhanced PP2A activity leads to
      HDAC4 dephosphorylation and the nuclear accumulation of HDAC4. Our results define
      a crucial role of the cellular localization of HDAC4 in the events leading to
      ataxia telangiectasia neurodegeneration.

PMID- 22466706
TI  - Identification and prioritization of bioaccumulable pharmaceutical substances
      discharged in hospital effluents.
AB  - The consumption of pharmaceuticals and their excretion in wastewater is a
      continuous source of pollution for aquatic ecosystems. In certain cases these
      compounds are found in the environment at concentrations high enough to cause
      disturbance in aquatic organisms. Aware of this problem hospitals are giving
      increasing attention to the nature of their effluents and their impact on the
      environment, by implementing more efficient effluent management policies. This
      concern is justified in view of the large volumes of toxic products consumed
      (detergents, disinfectants, pharmaceuticals, chemical reagents, radioactive
      elements, etc.). Moreover, these effluents usually do not undergo any specific
      treatment before being discharged into urban sewage networks. In this article, we
      present a method for selecting the pharmaceuticals discharged in hospital
      effluents that have the worst impact on the aquatic ecosystem, primarily based on
      their bioaccumulation potential. This study focused on the pharmaceuticals
      consumed at the Hospices Civils de Lyon (HCL), the second largest hospital
      structure in France (5200 hospital beds). Of the 960 substances consumed in HCL
      hospitals, a shortlist of 70 substances considered as being potentially
      bioaccumulable was established. The use of aggravating factors of risk has then
      led to the final selection of 14 priority compounds. They include 4 compounds
      consumed in large quantities in HCL hospitals, 6 endocrine disruptors and 4
      potentially ecotoxic compounds. For all these compounds, it is now advisable to
      verify their bioaccumulation potential experimentally and confirm their presence
      in the environment. In addition, in order to monitor the risk relating to
      possible contamination of the food chain, it will be necessary to measure
      accumulated dose levels in species of different trophic levels. Lastly, chronic
      ecotoxicity tests will permit evaluating the danger and risk that some of these
      substances may represent for aquatic ecosystems.

PMID- 22466705
TI  - Editing T cell specificity towards leukemia by zinc finger nucleases and
      lentiviral gene transfer.
AB  - The transfer of high-avidity T cell receptor (TCR) genes isolated from rare tumor
      specific lymphocytes into polyclonal T cells is an attractive cancer
      immunotherapy strategy. However, TCR gene transfer results in competition for
      surface expression and inappropriate pairing between the exogenous and endogenous
      TCR chains, resulting in suboptimal activity and potentially harmful unpredicted
      antigen specificities of the resultant TCRs. We designed zinc-finger nucleases
      (ZFNs) that promoted the disruption of endogenous TCR beta- and alpha-chain
      genes. Lymphocytes treated with ZFNs lacked surface expression of CD3-TCR and
      expanded with the addition of interleukin-7 (IL-7) and IL-15. After lentiviral
      transfer of a TCR specific for the Wilms tumor 1 (WT1) antigen, these TCR-edited
      cells expressed the new TCR at high levels, were easily expanded to near purity
      and were superior at specific antigen recognition compared to donor-matched,
      unedited TCR-transferred cells. In contrast to unedited TCR-transferred cells,
      the TCR-edited lymphocytes did not mediate off-target reactivity while
      maintaining their anti-tumor activity in vivo, thus showing that complete editing
      of T cell specificity generates tumor-specific lymphocytes with improved
      biosafety profiles.

PMID- 22466707
TI  - Production costs of biodiversity zones on field and forest margins: a case study
      in Finland.
AB  - This paper estimates and compares the costs incurred to a private landowner from
      establishing and managing 25-m wide biodiversity zones on field and forest
      margins in southern Finland. Crop and timber prices being at their long-term
      averages, current agricultural support paid and the real discount rate 3%, the
      average annual net costs per hectare of field and forest biodiversity zones were
      ?30 ha(-1) and ?108 ha(-1), respectively, the field zones being the less costly
      alternative in 95% of cases. This result is mainly due to the poor productivity
      of field cultivation relative to timber production under boreal climate
      conditions. In addition to soil quality, the initial stand structure affects the
      costs of both biodiversity zone types. It is less costly for a landowner to
      establish biodiversity zones in forests where no final felling is imminent but
      which already contain some tree volume. In field biodiversity zones, costs are
      slightly lower on fields where forest shading is great. Uneven-aged management
      practiced in forest biodiversity zones was found to lead to a 3-32% reduction in
      the net present value of forest land compared to conventional forest management.
      An increase in the real discount rate increases the relative efficiency of forest
      biodiversity zones.

PMID- 22466708
TI  - A rare papillary fibroelastoma of the tricuspid valve in a 4-year-old girl.

PMID- 22466709
TI  - Oxygen pulse kinetics in Fontan patients during treadmill ramp protocol
      cardiopulmonary exercise testing.
AB  - After single-ventricle palliation, patients have variable long-term functional
      outcomes. Cardiopulmonary exercise testing (CPET) is an assessment tool used to
      quantify functional outcome. Oxygen pulse kinetics during CPET, which can be an
      important indicator of dynamic changes in stroke volume reserve, has not been
      systematically studied in this population. This study aimed to analyze oxygen
      pulse kinetics during a treadmill ramp protocol among patients with Fontan
      physiology compared with that of normal subjects and to explore the ability of
      oxygen pulse kinetics to define functional status further. Peak oxygen pulse and
      change in oxygen pulse during ramp treadmill CPET were retrospectively collected
      and compared between 44 Fontan patients and 85 age- and sex-matched control
      subjects. The peak oxygen pulse was significantly lower in the Fontan group (9.80
      +/- 4.11 ml/beat) than in the control group (13.62 +/- 4.7 ml/beat) (p <= 0.001).
      The resting oxygen pulse did not differ between the two groups (3.13 +/- 1.23 vs.
      3.09 +/- 1.33 ml/beat; p = 0.88). The oxygen pulse was higher in the patients
      with chronotropic insufficiency, but the difference was not statistically
      significant (11.11 +/- 4.97 vs. 9.25 +/- 3.63 ml/beat; p = 0.17). Regression
      analysis showed a significant difference in the slope of the oxygen pulse-to
      workload relationship. The Fontan group showed no relation between degree of
      reduction in the oxygen pulse from peak to end of exercise and the underlying
      defect, peak heart rate, peak oxygen consumption, ventilatory anaerobic threshold
      (VAT), expired volume (VE)/carbon dioxide output (VCO(2)) at the VAT, maximum
      heart rate, or minimum oxygen saturation. Analysis of oxygen pulse kinetics in
      Fontan patients suggests that there is an early and progressive limitation in
      stroke volume compared with control subjects. This limitation may be partially
      masked by increased oxygen extraction. In patients with chronotropic
      insufficiency, absolute or body surface area-indexed oxygen pulse may be higher
      than in those with a normal heart rate response. A composite assessment of the
      oxygen pulse and oxygen pulse kinetics, including the oxygen pulse slope and the
      percentage of reduction in oxygen pulse from peak to end of exercise, may allow a
      more comprehensive assessment of the degree of cardiac limitation in this group
      of patients.

PMID- 22466710
TI  - Does treatment of patent ductus arteriosus with cyclooxygenase inhibitors affect
      neonatal regional tissue oxygenation?
AB  - The effect of patent ductus arteriosus (PDA) treatment with cyclooxygenase (COX)
      inhibitors (indomethacin [INDO] and ibuprofen [IBU]) on regional oxygenation
      requires further clarification. The authors hypothesized that both INDO and IBU
      reduce regional tissue oxygenation in preterm neonates with PDA but that the risk
      is not uniform for different tissues and other factors may contribute. Regional
      cerebral (rSO(2-C)), renal (rSO(2-R)), and mesenteric (rSO(2-M)) tissue
      oxygenation measured by near-infrared spectroscopy and peripheral arterial oxygen
      saturation measured by pulse oximetry were recorded simultaneously before,
      during, and after treatment with the first dose of INDO or IBU in very preterm
      born infants with PDA. Tissue-specific fractional oxygen extraction (FOE) was
      calculated using the rSO(2-C), rSO(2-R), rSO(2-M), and corresponding SpO(2)
      measurements. The findings showed a significant reduction in rSO(2-C), rSO(2-R),
      and rSO(2-M) and an increase in regional FOE after treatment with COX inhibitors
      in approximately one third of the 38 enrolled infants, which were associated with
      increased baseline regional tissue oxygen saturation (p < 0.01). However, the
      infants with posttreatment reduction of tissue oxygenation had significantly
      lower baseline rSO(2-C) (66.7 +/- 8.1 vs 69.7 +/- 8.1 %), rSO(2-R) (55.2 +/- 10.8
      vs 62.7 +/- 11.8 %) and especially rSO(2-M) (37.8 +/- 11.4 vs 46.7 +/- 16.0 %)
      than the neonates with unchanged or increased tissue oxygenation. The two groups
      did not differ in terms of the risk for posttreatment reduction in regional
      tissue oxygenation with respect to either INDO or IBU treatment and their
      respective blood levels. Treatment of PDA with either INDO or IBU is associated
      with a 30-40 % risk for a reduction in regional tissue oxygenation, which is more
      pronounced in mesenteric tissue than in cerebral or renal tissue. Despite the
      inconsistency, reduction of regional tissue oxygenation in preterm infants with
      PDA is more likely associated with the administration of INDO than with the
      administration of IBU.

PMID- 22466712
TI  - Anti-citrullinated peptide antibodies in the serum of heavy smokers without
      rheumatoid arthritis. A differential effect of chronic obstructive pulmonary
      disease?
AB  - The objective of this study is to analyse the frequency and levels of anti
      citrullinated peptide/protein antibodies (ACPA) in the serum of non-rheumatoid
      arthritis (RA) heavy smokers with and without chronic obstructive pulmonary
      disease (COPD) and compare them with healthy never smokers and patients with RA.
      Serum samples of 110 heavy smokers without RA, 209 healthy never smokers and 134
      patients with RA were tested for ACPA using a commercial anti-cyclic
      citrullinated peptide antibodies (CCP2) test and a homemade chimeric
      fibrin/filaggrin citrullinated synthetic peptide (anti-CFFCP) ELISA test. The
      frequency of positive results and autoantibody levels were compared between
      groups. The prevalence of the two types of ACPA was slightly higher in heavy
      smokers than in never smokers, although the difference was not significant, and
      significantly lower than in RA patients. The highest prevalence of positive ACPA
      in heavy smokers was found in subjects with COPD (7.4% of positive anti-CFFCP in
      patients with COPD in comparison with 2.4% in never smokers: OR 3.26; 95% CI 0.85
      12.6, p = 0.089). Mean serum levels of ACPA in heavy smokers were not
      significantly different from those of never smokers. Heavy smokers with COPD had
      significantly higher levels of anti-CFFCP than those without COPD, although
      almost all patients had serum levels below the cut-off values. The prevalence of
      ACPA in heavy smokers without RA is low, but seems to be higher in heavy smokers
      with COPD. Larger studies are necessary to confirm these findings and determine
      the relationship between ACPA and lung disease.

PMID- 22466713
TI  - Laparoscopic live donor left lateral sectionectomy is safe and feasible for
      pediatric living donor liver transplantation.
AB  - BACKGROUND/AIMS: Compared to the open method of left lateral sectionectomy, the
      laparoscopic method has demonstrated shorter hospital stay with less bleeding and
      complications and is becoming the gold standard procedure. We report our
      experience with 15 Iaparoscopic left lateral sectionectomies performed during
      PLDLTs from May 2008. METHODOLOGY: From May 2008 to April 2010, there were 15
      cases where laparoscopic left lateral sectionectomy was performed for donor
      hepatectomy. All cases were performed by a sin-gle surgeon. RESULTS: The mean
      size of the actual graft was 248.8+/-52.8mL (range 150-350). The mean operation
      time was 331.3+63.1 minutes (range 220-480),the mean blood loss was 410.0+71.2mL
      (range 250-500) and the mean warm ischemic time was 5.8+1.6 minutes (range 4-10).
      The mean time to oral intake was 2.0+/-0.3 days (range 1-3) and the mean hospital
      stay was 7.1+0.8 days (range 6-10). There were no complications or deaths among
      donors postoperative-ly. CONCLUSIONS: We believe it is a safe and reproducible
      procedure and an especially useful procedure for young mother donors who desire
      small wounds and rapid recovery.

PMID- 22466715
TI  - Incorporation of Mo and W into nanostructured BiVO4 films for efficient
      photoelectrochemical water oxidation.
AB  - Porous, nanostructured BiVO4 films are incorporated with Mo and W by simultaneous
      evaporation of Bi, V, Mo, and W in vacuum followed by oxidation in air. Synthesis
      parameters such as the Bi : V : Mo : W atomic ratio and deposition angle are
      adjusted to optimize the films for photoelectrochemical (PEC) water oxidation.
      Films synthesized with a Bi : V : Mo : W atomic ratio of 46 : 46 : 6 : 2 (6% Mo,
      2% W) demonstrate the best PEC performance with photocurrent densities 10 times
      higher than for pure BiVO4 and greater than previously reported for Mo and W
      containing BiVO4. The films consist of a directional, nanocolumnar layer beneath
      an irregular surface structure. Backside illumination utilizes light scattering
      off the irregular surface structure resulting in 30-45% higher photocurrent
      densities than for frontside illumination. To improve the kinetics for water
      oxidation Pt is photo-deposited onto the surface of the 6% Mo, 2% W BiVO4 films
      as an electrocatalyst. These films achieve quantum efficiencies of 37% at 1.1 V
      vs. RHE and 50% at 1.6 V vs. RHE for 450 nm light. 

PMID- 22466714
TI  - Comparative mapping, genomic structure, and expression analysis of eight pseudo
      response regulator genes in Brassica rapa.
AB  - Circadian clocks regulate plant growth and development in response to
      environmental factors. In this function, clocks influence the adaptation of
      species to changes in location or climate. Circadian-clock genes have been
      subject of intense study in models such as Arabidopsis thaliana but the results
      may not necessarily reflect clock functions in species with polyploid genomes,
      such as Brassica species, that include multiple copies of clock-related genes.
      The triplicate genome of Brassica rapa retains high sequence-level co-linearity
      with Arabidopsis genomes. In B. rapa we had previously identified five orthologs
      of the five known Arabidopsis pseudo-response regulator (PRR) genes that are key
      regulators of the circadian clock in this species. Three of these B. rapa genes,
      BrPRR1, BrPPR5, and BrPPR7, are present in two copies each in the B. rapa genome,
      for a total of eight B. rapa PRR (BrPRR) orthologs. We have now determined
      sequences and expression characteristics of the eight BrPRR genes and mapped
      their positions in the B. rapa genome. Although both members of each paralogous
      pair exhibited the same expression pattern, some variation in their gene
      structures was apparent. The BrPRR genes are tightly linked to several flowering
      genes. The knowledge about genome location, copy number variation and structural
      diversity of these B. rapa clock genes will improve our understanding of clock
      related functions in this important crop. This will facilitate the development of
      Brassica crops for optimal growth in new environments and under changing
      conditions.

PMID- 22466716
TI  - Low income/socio-economic status in early childhood and physical health in later
      childhood/adolescence: a systematic review.
AB  - To systematically review the literature on the relationship between early
      childhood low income/socioeconomic status (SES) and physical health in later
      childhood/adolescence, to identify gaps in the literature and to suggest new
      avenues for research. A systematic search of electronic databases from their
      start date to November 2011 was conducted to identify prospective longitudinal
      studies in industrialized countries with a measure of low income/SES in the first
      5 years of life and physical health outcomes in later childhood or adolescence.
      STROBE criteria were used to assess study quality. Risk estimates were expressed
      as odds ratios with 95 % confidence intervals where possible. Heterogeneity of
      studies precluded meta-analysis. Nine studies fulfilled the inclusion criteria.
      Significant associations of early childhood low income/SES with activity-limiting
      illness, parent-reported poor health status, acute and recurrent infections,
      increasing BMI percentile and hospitalization were reported. Results for parent
      reported asthma were less consistent: there was a significant association with
      low income/SES in early childhood in 2 studies but null findings in 3 others.
      This systematic review of the association of early childhood low income/SES with
      physical health status in later childhood and adolescence shows that, in contrast
      to the extensive literature on the impact of poor childhood social circumstances
      on adult health, the evidence base is limited. The literature points to some
      associations of early low income/SES with later poor health status, but many key
      research questions remain unanswered. Implications for further research are
      considered.

PMID- 22466717
TI  - Symptoms of depression postpartum and 12 years later-associations to child mental
      health at 12 years of age.
AB  - Children of depressed mothers have been shown to express behaviour problems to a
      greater extent than children of non-depressed mothers. The purpose of this study
      was to examine the persistence of depressive symptoms in mothers and to evaluate
      the relative importance of symptoms of postpartum depression (PPD) and concurrent
      maternal symptoms of depression, on child behaviour at age 12. A birth cohort of
      1,707 children and their mothers was followed from 3 months after birth to 12
      years after birth. Self-reported symptoms of depression in mothers were assessed
      at baseline and 12-year follow-up where 893 mothers (52.3 %) and their children
      participated. The mothers' reports on the behaviour of their children at age 12
      were used. Multivariate analysis was used to assess factors that increased the
      risk of child behaviour problems. At baseline, 10.4 % scored above the cutoff for
      symptoms of postpartum depression. At follow up, 18.2 % scored above the cutoff
      for depressive symptoms. Multivariate analysis showed that ongoing maternal
      symptoms of depression, as distinct from PPD-symptoms, was the strongest
      predictor of child behaviour problems at age 12. The gender of the child and
      socio-demographic factors at baseline were additional factors that affected the
      risk of behaviour problems in the 12 year old children. Children of mothers who
      reported symptoms of depression, both postpartum and at follow-up, were at a
      greater risk of behaviour problems compared to children of women with no
      depressive symptoms on either occasion. Our findings indicate that recurrent and
      ongoing maternal depressive symptoms significantly increase the risk of child
      behaviour problems as reported by mothers, while symptoms of PPD do not seem to
      result in an increased risk of behaviour problems in 12 year olds. High maternal
      socio-demographic life stress at childbirth constitutes an important risk factor
      for later child behaviour problems.

PMID- 22466718
TI  - Language and immigrant status effects on disparities in Hispanic children's
      health status and access to health care.
AB  - The objective of this study is to estimate Hispanic/non-Hispanic (nH)-white
      health disparities and assess the extent to which disparities can be explained by
      immigrant status and household primary language. The 2007 National Survey of
      Children's Health was funded by the Maternal and Child Health Bureau, and
      conducted by Centers for Disease Control and Prevention's National Center for
      Health Statistics as a module of the State and Local Area Integrated Telephone
      Survey. We calculated disparities for various health indicators between Hispanic
      and nH-white children, and used logistic regression to adjust them for socio
      economic and demographic characteristics, primary language spoken in the
      household, and the child's immigrant status. Controlling for language and
      immigrant status greatly reduces health disparities, although it does not
      completely eliminate all disparities showing poorer outcomes for Hispanic
      children. English-speaking and nonimmigrant Hispanic children are more similar to
      nH-white children than are Hispanic children in non-English speaking households
      or immigrant children. Hispanic/nH-white health disparities among children are
      largely driven by that portion of the Hispanic population that is either newly
      arrived to this country or does not speak primarily English in the household.

PMID- 22466719
TI  - Racial/ethnic variation in breastfeeding across the US: a multilevel analysis
      from the National Survey of Children's Health, 2007.
AB  - We examined whether differences across states in race/ethnicity-specific
      breastfeeding rates are due solely to state differences in individual factors
      associated with breastfeeding or additionally, certain state "contextual"
      factors. Using data from the 2007 National Survey of Children's Health,
      multilevel models examined whether state variability in race/ethnicity specific
      breastfeeding initiation and duration to 6 months were explained by (1)
      individual sociodemographic characteristics of women in states, and (2) an
      aggregate state measure of the availability of evidence-based maternity care
      services related to breastfeeding. Observed variability of race/ethnicity
      specific breastfeeding rates was only minimally reduced after adjusting for
      sociodemographic characteristics (Median Odds Ratios (MOR), breastfeeding
      initiation: non-Hispanic White = 1.46, non-Hispanic Black = 2.26; Hispanic =
      1.89. MOR, breastfeeding for 6 months: non-Hispanic White = 1.36, non-Hispanic
      Black = 1.84; Hispanic = 1.56). Overall variability in the degree of state gaps
      changed little in adjusted models (breastfeeding initiation: non-Hispanic Black
      sigma(2) = 0.74, se 0.28, Hispanic sigma(2) = 0.45, se 0.11; breastfeeding to 6
      months: non-Hispanic Black sigma(2) = 0.41, se 0.10, Hispanic sigma(2) = 0.22, se
      0.05). The measure of maternity care services was positively associated with
      breastfeeding overall but generally did not explain a substantial portion of
      between-state variability nor the overall variability in racial/ethnic gaps.
      Contextual sources of variation in state breastfeeding practices and disparities
      remain poorly understood. Differences in the socioeconomic makeup of states do
      not fully explain variability. The association of state breastfeeding rates and
      disparities with relevant policy and practice factors should be further
      investigated.

PMID- 22466720
TI  - A literature review of spontaneous evisceration in paediatric umbilical hernias.
AB  - Umbilical hernias occur frequently in children but complications are very rare
      and thus surgery is not routinely indicated. In this literature review, we report
      19 cases of spontaneous evisceration of abdominal contents through umbilical
      hernias. Precipitating causes included umbilical ulceration or sepsis, crying,
      respiratory infection, intussusception and ascites. Management involved
      resuscitation and surgical repair. Mortality is low. As the incidence of
      spontaneous rupture is very low, the current management of an umbilical hernia
      remains appropriate. However, we encourage physicians to be aware of the
      potential risk factors for spontaneous rupture and in these patients expedite
      surgical repair.

PMID- 22466721
TI  - Psychometric assessment of the patient activation measure short form (PAM-13) in
      rural settings.
AB  - PURPOSE: The patient activation measure short form (PAM-13) assesses patients'
      self-reported health management skills, knowledge, confidence, and motivation. We
      used item response theory to evaluate the psychometric properties of the PAM-13
      utilized in rural settings. METHODS: A Rasch partial credit model analysis was
      conducted on the PAM-13 instrument using a sample of 812 rural patients recruited
      by providers and our research staff. Specially, we examined dimensionality, item
      fit, and quality of measures, category response curves, and item differential
      functioning. Convergent and divergent validities were also examined. FINDINGS:
      The PAM-13 instrument has excellent convergent and divergent validities. It is
      fairly unidimensional, and all items fit the Rasch model well. It has relatively
      high person and item reliability indices. Majority of the items were free of item
      differential functioning. There were, however, some issues with ceiling effects.
      Additionally, there was a lack of responses for category one across all items.
      CONCLUSIONS: Patient activation measure short form (PAM-13) performs well in some
      areas, but not all. In general, more items need to be added to cover the upper
      end of the trait. The four response categories of PAM-13 should be collapsed into
      three.

PMID- 22466723
TI  - Fractional charge and statistics in the fractional quantum spin Hall effect.
AB  - In this paper, we consider there exist two types of fundamental quasihole
      excitation in the fractional quantum spin Hall state and investigate their
      topological properties by both Chern-Simons field theory and the Berry phase
      technique. By the two different techniques, we obtain the identical charge and
      statistical angle for each type of quasihole, as well as the identical mutual
      statistics between two different types of quasihole excitation.

PMID- 22466724
TI  - Development of efficient catalytic arylation of aldehydes with thioether
      imidazolinium carbene ligands.
AB  - Effective methods of ligand design have been highly sought due to the significant
      roles of ligands in controlling metal catalyses. In particular, easy-to-handle
      ligands to realize high reaction efficacy, substrate tolerance, and environmental
      friendliness are desirable. Novel bidentate ligands containing N-heterocyclic
      carbene and thioether moieties were developed based on findings of hemilabile
      coordination, whose precursors were crystalline solids stable enough to handle
      and store in the air. The thioether-imidazolinium carbene ligand successfully
      brought out high catalyst performance of palladium in the catalytic arylation of
      aldehydes with organoboron reagents, which tolerated a diverse range of
      substrates including poorly reactive, sterically hindered, and heterocyclic
      compounds. This process was applied to gram-scale synthesis using only water as
      solvent with high efficiency and also achieved the effective one-pot synthesis of
      3-arylphthalides known as useful biologically active agents and important
      synthetic intermediates for naturally occurring compounds.

PMID- 22466725
TI  - Comparison between original and generic versions of ceftriaxone sodium
      preparation for injection: compatibility with calcium-containing product.
AB  - The purpose of this study was to compare the compatibility of ROCEPHINE(r)
      Intravenous, the original manufacturer's ceftriaxone sodium preparation for
      injection, and seven generic versions thereof, with various calcium chloride
      injection 2%. The influence of calcium ion concentration, storage time and
      shaking strength on the appearance and quantity of insoluble microparticles in
      mixed solutions was examined using a light obscuration particle counter. In all
      products, the observed number of insoluble microparticles was proportional to the
      calcium ion concentration, storage time and shaking strength after the addition
      of calcium chloride solution. In several of the generic products, the number of
      insoluble microparticles was significantly higher than those of the original
      product, while in others it was lower. We evaluated the quality of the original
      and 7 generic preparations, measured the content of impurity and pH of the
      various ceftriaxone solutions, as impurity content and pH of solution are
      possible factor affecting compatibility. Three impurities were found in all
      products. The impurity content of several generic products, as estimated from
      their peak area on high performance liquid chromatography (HPLC), was
      significantly lower than that of the original product. pH of solution was
      difference between products. Although it was difficult that impurity and pH of
      solution verify critical factor affecting compatibility. The results show that
      there are differences in the appearance of insoluble microparticles between the
      original product and seven generic products, when calcium chloride injection 2%
      solution is added to the product.

PMID- 22466726
TI  - Synthesis and structure of the beta-carboline derivatives and their binding
      intensity with cyclin-dependent kinase 2.
AB  - Series of 3-substituted of 6-aminosulfonyl-beta-carbolines were designed and
      synthesized. In addition, the binding mode of these beta-carboline derivatives
      with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence
      measurements and molecular docking calculation. The results showed that
      replacement of 3-cyclohexylmethoxy group will increase the hydrophobic binding
      interaction with the deep hydrophobic pocket of CDK2 correlate to the higher
      binding intensity.

PMID- 22466727
TI  - Study of the physicochemical properties of tulobuterol dry syrups using taste and
      smell sensors.
AB  - The purpose of the present study was to evaluate the taste and smell of
      Tulobuterol Dry Syrup (TB-DS) in its original form (formulation A) and generic
      form (formulations B and C) by means of gustatory sensation tests and taste and
      smell sensors. In addition, the physicochemical properties of the syrups in a
      solid state were compared. Evaluation of sweetness with a powdered sample
      revealed significant differences between formulation A and formulation B and
      between formulation B and formulation C. In contrast, the results of principal
      component analysis (PCA) with a taste sensor revealed differences in principal
      component 1 (PC 1) among formulations A, B, and C. Smell sensor measurement of
      powdered samples revealed differences in products in terms of only PC 1, but
      these results were not related to the results of gustatory sensation testing with
      a smell sensor. Measurement of particle size distribution and scanning electron
      microscopy revealed differences in the particle diameter and particle surface
      shape for each product. Formulation B had the strongest absorption in the near
      infrared spectrum, followed by formulation A and then formulation C. Accordingly,
      differences in preparations were presumably caused by variations in manufacturing
      specifications, such as types of additives and their content and coating methods
      used. In other words, the characteristics of each product were revealed by
      evaluation of their physical properties, sensing of taste and smell, and human
      gustatory sensation tests.

PMID- 22466728
TI  - The reactivity of gem cyanoester ketene dithiolates towards the development of
      potent antioxidant heterocycles.
AB  - The reactivity of gem cyanoester ketene dithiolates towards the development of a
      variety of heterocycles was studied and tested for antioxidant property. The
      compounds bis benzoxazolylmethylthiomethylene pyrazoles and isoxazoles displayed
      excellent radical scavenging activity when compared with the standard ascorbic
      acid.

PMID- 22466729
TI  - Polymer combination increased both physical stability and oral absorption of
      solid dispersions containing a low glass transition temperature drug:
      physicochemical characterization and in vivo study.
AB  - The purpose of this study was establishing a solid dispersion formulation
      containing a low glass transition temperature (T(g)) and poorly water-soluble
      drug. Drug/polymer blends with differing physicochemical stabilities and oral
      absorption were prepared from copolyvidone (PVP-VA), polyvinylpyrrolidone (PVP)
      or hydroxypropylmethylcellulose (HPMC) by a hot melt extrusion. HPMC drastically
      increased the drug oral absorption property, while PVP-VA or PVP stabilized solid
      dispersions during storage by increasing the T(g) in proportion to polymer
      concentration. Experimental T(g) values corresponded closely with theoretical
      T(g) values; indeed, the T(g) values of solid dispersion with HPMC did not
      increase significantly compared to the T(g) value for the drug alone. A solid
      dispersion formulation incorporating two different polymers-HPMC and either PVP
      VA or PVP-maintained increased T(g), physicochemical stability, solubility, and
      bioavailability of the solid dispresions owing to each polymer. These findings
      suggested that both oral absorption and physicochemical stability of low-T(g)
      drug will be improved using less amount of solid dispersion of combined two
      polymers than polymer alone.

PMID- 22466730
TI  - NO-NSAIDs. Part 3: nitric oxide-releasing prodrugs of non-steroidal anti
      inflammatory drugs.
AB  - In continuation of our efforts to discover novel nitric oxide-releasing non
      steroidal anti-inflammatory drugs (NO-NSAIDs) as potentially "Safe NSAIDs," we
      report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of
      commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen,
      ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO
      releasing disulfide linker attached to a parent NSAID via linkages such as an
      ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25
      30) or an amide (compounds 31-33). Among these NO-NSAIDs, the ester-containing NO
      aspirin (9), NO-diclofenac (10), NO-naproxen (11), and the imide-containing NO
      aspirin (25), NO-flurbiprofen (27) and NO-ketoprofen (28) have shown promising
      oral absorption, anti-inflammatory activity and NO-releasing property, and also
      protected rats from NSAID-induced gastric damage. NO-aspirin compound 25, on
      further co-evaluation with aspirin at equimolar doses, exhibited comparable dose
      dependent pharmacokinetics, inhibition of gastric mucosal prostaglandin E(2)
      (PGE(2)) synthesis and analgesic properties to those of aspirin, but retained its
      gastric-sparing properties even after doubling its oral dose. These promising NO
      NSAIDs could therefore represent a new class of potentially "Safe NSAIDs" for the
      treatment of arthritic pain and inflammation.

PMID- 22466731
TI  - Preparation, characterization and in vivo evaluation of antihyperglycemic
      activity of microwave generated repaglinide solid dispersion.
AB  - The influence of microwave technology on the in vitro dissolution rate and in
      vivo antihyperglycemic activity of a poorly water soluble drug, repaglinide (RG)
      was studied. Solid dispersions were prepared by conventional fusion method and
      microwave method using poloxamer 188. The dispersions were characterized by
      solubility study, dissolution study, Fourier transform infrared spectroscopy (FT
      IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and
      scanning electron microscopy (SEM). Microwave generated solid dispersions
      exhibited remarkable improvement in solubility and dissolution rate compared to
      that of pure RG. Results of DSC, XRD and SEM study showed conversion of
      crystalline form of RG to amorphous form. In vivo studies revealed that the
      microwave generated solid dispersion showed significant improvements in
      antihyperglycemic activity as compared to RG alone, thus confirming the advantage
      of improved pharmacological activity of RG by microwave method. In conclusion,
      microwave method could be considered as simple, efficient and solvent free
      promising alternative method to prepare solid dispersion of poorly water soluble
      drug RG with significant enhancement in solubility, dissolution rate and
      antihyperglycemic activity.

PMID- 22466732
TI  - Synthesis and pharmacological evaluation of 3-amino-1-(5-indanyloxy)-2-propanol
      derivatives as potent sodium channel blockers for the treatment of stroke.
AB  - In investigating potent sodium (Na(+)) channel blockers for the treatment of
      ischemic stroke, we synthesized a novel series of 3-amino-1-(5-indanyloxy)-2
      propanol derivatives and evaluated their inhibitory effects on neuronal Na(+)
      channels. The 3-amino-1-(5-indanyloxy)-2-propanol derivatives exhibited potent
      blocking activity for Na(+) channels and a significantly low affinity for
      dopamine D(2) receptors, which demonstrates a minimal clinical risk for
      extrapyramidal side effects. In particular, compound 4b, a 3-amino-1-(5
      indanyloxy)-2-propanol derivative bearing a benzimidazole moiety, showed
      desirable neuroprotective activity in a rat transient middle cerebral artery
      occlusion model. Furthermore, compound 4b displayed a high binding affinity for
      neurotoxin receptor site 2 of the Na(+) channels, which suggests that 4b would
      act as a use-dependent Na(+) channel blocker in sustained depolarization during
      ischemic stroke.

PMID- 22466733
TI  - Caffeic acid oligomers with hyaluronidase inhibitory activity from Clinopodium
      gracile.
AB  - Eight new caffeic acid oligomers, clinopodic acids J-Q (1-8), were isolated from
      whole plants of Clinopodium gracile, together with nine known caffeic acid
      oligomers. The caffeic acid oligomers with two to four dihydrobenzofuran rings
      were isolated as natural products for the first time. Clinopodic acid M (4)
      showed the strongest hyaluronidase inhibitory activity, IC(50) (19 uM) among the
      22 compounds isolated from this plant.

PMID- 22466734
TI  - Synthesis of oxovanadium complexes and their apoptosis-inducing activity in
      leukemia cells.
AB  - Vanadium complexes with different ligands were synthesized and evaluated for
      antiproliferative activity on U937 cells. The alkyl chain length of the ligands
      affected the antiproliferative activity, and two complexes-3b and 4-exhibited
      strong activities with IC(50) values of 6.02 and 3.90 MUM respectively. Annexin V
      staining and DNA ladder formation indicated that these complexes induced
      apoptosis in U937 cells.

PMID- 22466735
TI  - Synthesis and anti-tumor activities of novel oxazinyl isoflavonoids.
AB  - The design, synthesis and biological evaluation of a novel series of oxazinyl
      isoflavonoids is described. Several analogs were shown to exhibit growth
      inhibitory effects against SKOV-3, DU-145 and HL-60 human colon cancer cell lines
      with IC(50) values in the micromolar range. The cellular potency of compounds 7e
      and 12h were found to have greater in vitro inhibitory activities than
      phenoxodiol, the parental compound currently in late-stage clinical trials for
      the treatment of cancer. The results shown are suitable for further lead
      optimization.

PMID- 22466736
TI  - Novel pyrimidinone derivatives: synthesis, antitumor and antimicrobial
      evaluation.
AB  - Starting from 6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile
      (4a-d), a series of mono- and dialkyl derivatives 5a-j and 6a, b was synthesized.
      Hydrazinolysis of 4a, b, d and 5d afforded the hydrazino derivatives 7a-c which
      were cyclised to give the triazolopyrimidinones 8a-c and the pyrimidotriazinones
      9a-c through the reaction with formic acid and chloroacetyl chloride,
      respectively. Most of the newly synthesized compounds were evaluated for their in
      vitro antitumor activity. Compounds 6a and b displayed promising anticancer
      activity against leukaemia, non-small cell lung, melanoma, and renal cancer. On
      the other hand, all compounds prepared were screened for their in-vitro
      antibacterial and antifungal activities. Compounds 5h and j showed significant
      activity against Staphylococcus aureus, while compounds 5e, 7c and 8c displayed
      moderate inhibitory activity against Candida albicans.

PMID- 22466737
TI  - On-line concentration and fluorescence determination HPLC for polycyclic aromatic
      hydrocarbons in seawater samples and its application to Japan Sea.
AB  - An on-line concentration and fluorescence determination HPLC for polycyclic
      aromatic hydrocarbons (PAHs) in seawater was proposed. An online concentration
      column packed with octadecyl polyvinyl alcohol polymer, a pump and a column
      switching valve were introduced in the conventional HPLC with a fluorescence
      detector. Only 1.0-100 mL seawater sample was introduced into the concentration
      column at 1.0 mL min(-1) without any other pretreatment except filtration. Then
      the trapped PAHs totally flew into the separation column and eluted separately to
      be detected fluorogenically. The proposed method had good linearity with
      correlation coefficients (r) ranged from 0.951 to 0.998, and limits of detection
      ranged from 0.002 to 0.50 ng L(-1) for 15 PAHs as 100 mL seawater was loaded. The
      sensitivity of the method was 10 to 100 times higher than those reported by other
      works. The proposed method was applied to the determination of PAHs in the
      seawater samples collected in the Japan Sea with satisfactory results and to
      check the present benzo[a]pyrene concentration at the beaches in Noto peninsula,
      Japan polluted with C-heavy oil spilled from the tanker in 1997.

PMID- 22466738
TI  - Relationship between diffusivity of water molecules inside hydrating tablets and
      their drug release behavior elucidated by magnetic resonance imaging.
AB  - We reported previously that sustained release matrix tablets showed zero-order
      drug release without being affected by pH change. To understand drug release
      mechanisms more fully, we monitored the swelling and erosion of hydrating tablets
      using magnetic resonance imaging (MRI). Three different types of tablets
      comprised of polyion complex-forming materials and a hydroxypropyl
      methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images
      of the hydrating tablets were acquired at intervals. Furthermore, apparent self
      diffusion coefficient maps were generated from diffusion-weighted imaging to
      evaluate the state of hydrating tablets. Our findings indicated that water
      penetration into polyion complex tablets was faster than that into HPMC matrix
      tablets. In polyion complex tablets, water molecules were dispersed homogeneously
      and their diffusivity was relatively high, whereas in HPMC matrix tablets, water
      molecule movement was tightly restricted within the gel. An optimal tablet
      formulation determined in a previous study had water molecule penetration and
      diffusivity properties that appeared intermediate to those of polyion complex and
      HPMC matrix tablets; water molecules were capable of penetrating throughout the
      tablets and relatively high diffusivity was similar to that in the polyion
      complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This
      study succeeded in characterizing the tablet hydration process. MRI provides
      profound insight into the state of water molecules in hydrating tablets; thus, it
      is a useful tool for understanding drug release mechanisms at a molecular level.

PMID- 22466739
TI  - Effect of solvent type on the nanoparticle formation of atorvastatin calcium by
      the supercritical antisolvent process.
AB  - The aims of this study were to identify how the solvent selection affects
      particle formation and to examine the effect of the initial drug solution
      concentration on mean particle size and particle size distribution in the
      supercritical antisolvent (SAS) process. Amorphous atorvastatin calcium was
      precipitated from seven different solvents using the SAS process. Particles with
      mean particle size ranging between 62.6 and 1493.7 nm were obtained by varying
      organic solvent type and solution concentration. By changing the solvent, we
      observed large variations in particle size and particle size distribution,
      accompanied by different particle morphologies. Particles obtained from acetone
      and tetrahydrofuran (THF) were compact and spherical fine particles, whereas
      those from N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) were
      agglomerated, with rough surfaces and relatively larger particle sizes.
      Interestingly, the mean particle size of atorvastatin calcium increased with an
      increase in the boiling point of the organic solvent used. Thus, for atorvastatin
      particle formation via the SAS process, particle size was determined mainly by
      evaporation of the organic solvent into the antisolvent phase. In addition, the
      mean particle size was increased with increasing drug solution concentration. In
      this study, from the aspects of particle size and solvent toxicity, acetone was
      the better organic solvent for controlling nanoparticle formation of atorvastatin
      calcium.

PMID- 22466740
TI  - Intramolecular [2+2] cycloaddition of homoallylketenes to bicyclo[2.1.1]hexan-5
      ones.
AB  - Intramolecular [2+2] cycloaddition of gamma,delta-unsaturated ketenes derived
      from hex-5-enoyl chloride derivatives gave bicyclo[2.1.1]hexan-5-ones with
      complete regioselectivity.

PMID- 22466741
TI  - Phenolic compounds from the aerial parts of Diplomorpha canescens.
AB  - One new C-methyl flavanone glucoside, farrerol 4'-O-beta-D-glucopyranoside (1)
      was isolated from the aerial parts of Diplomorpha canescens (MEISN.) C. A. MEYER.
      Fourteen known phenolic compounds such as farrerol (2), luteolin 7-methyl ether 5
      O-beta-D-glucopyranoside (3), (-)-pinoresinol (4), (-)-lariciresinol (5), (-)
      dihydrosesamin (6), (+/-)-dehydrodiconiferyl alcohol (7), rutarensin (8),
      umbelliferone (9), coniferyl aldehyde (10), sinapyl aldehyde (11), p-coumaric
      acid methyl ester (12), p-hydroxybenzaldehyde (13), p-hydroxyacetophenone (14)
      and syringaldehyde (15) were also isolated for the first time from this plant.
      Structure of 1 was determined on the basis of spectroscopic data including two
      dimensional (2D)-NMR, circular dichroism (CD) and by the application of Klyne's
      rule.

PMID- 22466742
TI  - An efficient synthesis of a potent anti-inflammatory agent, viscolin, and its
      inducible nitric oxide synthase inhibitory activity.
AB  - A new and efficient synthetic pathway employed the aldol condensation between the
      acetophenone (3) and vanillin derivative (4) resulted in the precursor chalcone
      intermediate (14). The target compound viscolin (1) could be afforded through the
      hydrogenation of the chalcone and followed by deprotection. The present strategy
      described the development of a more efficient procedure that allowed large-scale
      production of viscolin for the further research of biological activity both in
      vitro and in vivo.

PMID- 22466743
TI  - Acid-promoted rearrangement of drimane type epoxy compounds and their application
      in natural product synthesis.
AB  - The reactions of (+/-)-alpha-epoxy drimenol (4) and (+/-)-alpha-epoxy drimenyl
      cyanide (6) with acids (proton acid or Lewis acid) selectively gave the
      rearranged aldehyde (+/-)-13 and (+/-)-15 having the hydroindane skeleton,
      respectively, while the reactions of (+/-)-4 and (+/-)-6 with Dibal-H selectively
      afforded the allyl alcohol (+/-)-14 and (+/-)-16, respectively. The reactions of
      (8aR)-6 and (8aS)-6 with Dibal-H were applied for the determination of the
      absolute structure of natural 7beta-acetoxy-ent-labda-8(17),13(14)E-dien-15-ol
      (18). The reaction of (+/-)-alpha-epoxy bicyclofarnesol (5) and (8aS)-5 with
      proton acid selectively provided the rearranged ketol (+/-)- and (8aS)-31 having
      the hydroindane skeleton, respectively. The optically active (8aS)-31 was
      converted to the natural (9S)-austrodoric acid (33).

PMID- 22466744
TI  - Improved pregnancy rates with luteinizing hormone supplementation in patients
      undergoing ovarian stimulation for IVF.
AB  - INTRODUCTION: Luteinizing hormone (LH) is believed to play a role in follicle
      maturation during the natural cycle. However, the need for co-treatment with
      recombinant LH (rLH) for controlled ovarian stimulation is controversial.
      PURPOSE: The primary objective of our study was to determine if pregnancy rates
      are improved when rLH is used in addition to rFSH for ovarian stimulation.
      Secondary outcomes were fertilization rate, implantation rate and live birth
      rate. METHODS: A retrospective cohort study was performed of 1565 IVF or ICSI
      cycles. Outcomes were compared between ovarian stimulation cycles from 2007 when
      rLH and rFSH was used (n = 765) to 2006 when rFSH only was used (n-800). RESULTS:
      Improved outcomes were found for rLH + rFSH versus rFSH alone for; pregnancy rate
      (61% and 54% respectively, p = 0.006), live birth rate (49% and 42% respectively,
      P = 0.01), fertilization rate (74% versus 72% respectively, p = 0.04 and
      implantation rate (41% versus 37% respectively, p = 0.03). CONCLUSIONS: Our large
      retrospective cohort study showed an improved pregnancy rate and live birth rate
      with rLH supplementation. This was associated with an improved fertilization and
      implantation rate and therefore may reflect an improvement in oocyte quality
      and/or uterine receptivity.

PMID- 22466745
TI  - Ovarian tissue cryopreservation for fertility preservation in cancer patients:
      successful establishment and feasibility of a multidisciplinary collaboration.
AB  - BACKGROUND: As advancements in cancer therapies have led to dramatic improvements
      in long term survival, there has been increasing interest in methods to expand
      fertility preservation options for cancer patients. METHODS: An experimental
      protocol for ovarian tissue cryopreservation was developed at the University of
      Pennsylvania for patients requiring gonadotoxic therapies. The protocol for
      adults was implemented at the Hospital of the University of Pennsylvania and for
      children at the Children's Hospital of Philadelphia in collaboration with the
      Oncofertility Consortium and the National Physicians Cooperative (NPC). RESULTS:
      A total of twenty-one patients (age range: 8-36 years) have cryopreserved ovarian
      tissue as part of this study. While patients had a variety of diagnoses and
      treatment exposures, 10/21 (48 %) patients suffered from hematologic disorders
      and 43 % were anticipating stem cell transplantation. No patients have requested
      that the tissue be used for clinical purposes. CONCLUSIONS: Ovarian tissue
      cryopreservation protocols can be implemented at pediatric and adult institutions
      through multi-disciplinary collaboration. While more research is needed to
      determine the safety and efficacy of ovarian tissue cryopreservation, this
      procedure provides hope for preserving the ability to have biological offspring
      to patients facing gonadotoxic therapies for a variety of medical conditions.

PMID- 22466746
TI  - Gradient-index meta-surfaces as a bridge linking propagating waves and surface
      waves.
AB  - The arbitrary control of electromagnetic waves is a key aim of photonic research.
      Although, for example, the control of freely propagating waves (PWs) and surface
      waves (SWs) has separately become possible using transformation optics and
      metamaterials, a bridge linking both propagation types has not yet been found.
      Such a device has particular relevance given the many schemes of controlling
      electromagnetic waves at surfaces and interfaces, leading to trapped rainbows,
      lensing, beam bending, deflection, and even anomalous reflection/refraction.
      Here, we demonstrate theoretically and experimentally that a specific gradient
      index meta-surface can convert a PW to a SW with nearly 100% efficiency. Distinct
      from conventional devices such as prism or grating couplers, the momentum
      mismatch between PW and SW is compensated by the reflection-phase gradient of the
      meta-surface, and a nearly perfect PW-SW conversion can happen for any incidence
      angle larger than a critical value. Experiments in the microwave region,
      including both far-field and near-field characterizations, are in excellent
      agreement with full-wave simulations. Our findings may pave the way for many
      applications, including high-efficiency surface plasmon couplers, anti-reflection
      surfaces, light absorbers, and so on.

PMID- 22466747
TI  - Sparsity-based single-shot subwavelength coherent diffractive imaging.
AB  - Coherent Diffractive Imaging (CDI) is an algorithmic imaging technique where
      intricate features are reconstructed from measurements of the freely diffracting
      intensity pattern. An important goal of such lensless imaging methods is to study
      the structure of molecules that cannot be crystallized. Ideally, one would want
      to perform CDI at the highest achievable spatial resolution and in a single-shot
      measurement such that it could be applied to imaging of ultrafast events.
      However, the resolution of current CDI techniques is limited by the diffraction
      limit, hence they cannot resolve features smaller than one half the wavelength of
      the illuminating light. Here, we present sparsity-based single-shot subwavelength
      resolution CDI: algorithmic reconstruction of subwavelength features from far
      field intensity patterns, at a resolution several times better than the
      diffraction limit. This work paves the way for subwavelength CDI at ultrafast
      rates, and it can considerably improve the CDI resolution with X-ray free
      electron lasers and high harmonics.

PMID- 22466748
TI  - Effect of metabolic regulators on aluminium uptake and toxicity in Matricaria
      chamomilla plants.
AB  - Phenolic metabolism of Al-exposed Matricaria chamomilla plants was modulated with
      four regulators: 2-aminoindane-2-phosphonic acid (AIP), salicylic acid (SA),
      sodium nitroprusside (SNP) and dithiothreitol (DTT). Physiological parameters
      (tissue water content, soluble proteins, reducing sugars, K+ content), root
      lignin content and free amino acids (increase in root proline and alanine) were
      the most affected in SA + Al variant, indicating negative impact of SA on Al
      induced changes. SNP showed the least visible impact, suggesting protective
      effect of nitric oxide. Complex comparison between Al alone and combined
      treatments revealed that SA and DTT stimulated increase in shoot phenolic acids
      (mainly vanillic acid), sum of flavonols and soluble phenols but decreased the
      levels of coumarin-related compounds (Z- and E-2-beta-D-glucopyranosyloxy-4
      methoxycinnamic acids), leading to elevation of shoot Al. Positive correlation
      between phenolic acids (mainly ferulic and chlorogenic acids), soluble phenols
      and total Al was found in the roots of SA and DTT variants. These events were not
      observed in AIP and SNP treatments. These data, to our knowledge for the first
      time, exactly confirm that phenolic metabolites may affect shoot Al uptake and
      this relation is rather positive in terms of simple phenols (and negative in
      terms of coumarin-related compounds).

PMID- 22466749
TI  - Non-enhanced ECG-gated respiratory-triggered 3-D steady-state free-precession MR
      angiography with slab-selective inversion: initial experience in visualisation of
      renal arteries in free-breathing children without renal artery abnormality.
AB  - BACKGROUND: ECG-gated non-enhanced balanced steady-state free precession (bSSFP)
      MR angiography requires neither breath-holding nor administration of contrast
      material. OBJECTIVE: To investigate the image quality of free-breathing ECG-gated
      non-enhanced bSSFP MR angiography of renal arteries in children. MATERIALS AND
      METHODS: Fourteen boys and seven girls (mean age, 9.7 years; range, 7 weeks-17
      years) with no history of renovascular disease were included. MRI was performed
      at 1.5 T. Subjective image quality of axial and coronal maximum-intensity
      projection reconstructions of four segments (I, aorta and renal artery ostium;
      II, main renal artery; III, segmental branches; IV, intrarenal vessels) was
      evaluated using a 4-point scale (4 = excellent, 3 = good, 2 = acceptable, 1 = non
      diagnostic). RESULTS: Image quality was excellent for segments I (mean +/- SD,
      3.9 +/- 0.3) and II (4.0 +/- 0.1), good for segment III (3.4 +/- 0.9) and
      acceptable for segment IV (2.3 +/- 1.1 ). Mean image quality did not differ
      between sedated and non-sedated children. CONCLUSION: bSSFP MR angiography
      enables visualisation of renal arteries in children.

PMID- 22466750
TI  - US and MRI of pediatric ocular masses with histopathological correlation.
AB  - We review our experience with unusual ocular pathologies, some mimicking
      retinoblastoma, that were referred to our institution during the past two
      decades. After presenting the imaging anatomy of the normal eye, we discuss
      pertinent clinical and pathological features, and illustrate the US and MRI
      appearance of retinoblastoma, medulloepithelioma, uveal melanoma, persistent
      fetal vasculature, Coats disease, corneal dermoid, retinal dysplasia and toxocara
      granuloma. Features useful in discriminating among these entities are emphasized.

PMID- 22466753
TI  - Understanding the functional properties of tools: chimpanzees (Pan troglodytes)
      and capuchin monkeys (Cebus apella) attend to tool features differently.
AB  - We examined whether eight capuchins and eight chimpanzees were able to retrieve a
      reward placed inside a tube, of varying length, by selecting the correct stick
      from different sets of three sticks differing in length (functional feature) and
      handle (non-functional feature). Moreover, to investigate whether seeing the
      stick inside the tube (visual feedback) improves performance, half of the
      subjects were tested with a transparent apparatus and the other half with an
      opaque apparatus. Phase 1 included (a) Training 1 in which each stick had a
      different handle and (b) Transfer 1 in which the handles were switched among
      sticks, so that the functional tool had the same length but a different handle
      than before. The seven chimpanzees and one capuchin that passed Transfer 1
      received Transfer 2. The other subjects received (a) Training 2, which used the
      same sticks from Phase 1 with handles switched in every trial, and (b) Transfer 2
      in which the tube was longer, all sticks had the same new handle, and the
      formerly longest tool became intermediate in length. Eight chimpanzees and three
      capuchins passed Transfer 2. Results showed that (1) chimpanzees applied
      relational structures in tool using tasks more quickly than capuchins and (2)
      capuchins required more varied experience to attend to the functional feature of
      the tool. Interestingly, visual feedback did not improve performance in either
      species.

PMID- 22466755
TI  - Corannulene and its penta-tert-butyl derivative co-crystallize 1:1 with pristine
      C60-fullerene.
AB  - The first X-ray structural determinations of pristine fullerene C(60),
      cocrystallized 1:1 with corannulene and with its pentaalkyl-substituted
      derivative, 1,3,5,7,9-penta-tert-butyl-corannulene, have now been achieved.

PMID- 22466756
TI  - Superhard F-carbon predicted by ab initio particle-swarm optimization
      methodology.
AB  - A simple (5 + 6 + 7)-sp(3) carbon (denoted as F-carbon) with eight atoms per unit
      cell predicted by a newly developed ab initio particle-swarm optimization
      methodology on crystal structure prediction is proposed. F-carbon can be seen as
      the reconstruction of AA-stacked or 3R-graphite, and is energetically more stable
      than 2H-graphite beyond 13.9 GPa. Band structure and hardness calculations
      indicate that F-carbon is a transparent superhard carbon with a gap of 4.55 eV at
      15 GPa and a hardness of 93.9 GPa at zero pressure. Compared with the previously
      proposed Bct-, M- and W-carbons, the simulative x-ray diffraction pattern of F
      carbon also well matches the superhard intermediate phase of the experimentally
      cold-compressed graphite. The possible transition route and energy barrier were
      observed using the variable cell nudged elastic band method. Our simulations show
      that the cold compression of graphite can produce some reversible metastable
      carbons (e.g. M- and F-carbons) with energy barriers close to diamond or
      lonsdaleite.

PMID- 22466757
TI  - Synthesis, structural characterization, antimicrobial and cytotoxic effects of
      aziridine, 2-aminoethylaziridine and azirine complexes of copper(II) and
      palladium(II).
AB  - The synthesis, spectroscopic and X-ray structural characterization of copper(II)
      and palladium(II) complexes with aziridine ligands as 2-dimethylaziridine
      HNCH(2)CMe(2) (a), the bidentate N-(2-aminoethyl)aziridines
      C(2)H(4)NC(2)H(4)NH(2) (b) or CH(2)CMe(2)NCH(2)CMe(2)NH(2) (c) as well as the
      unsaturated azirine NCH(2)CPh (d) are reported. Cleavage of the cyclometallated
      Pd(II) dimer [MU-Cl(C(6)H(4)CHMeNMe(2)-C,N)Pd](2) with ligand a yielded compound
      [Cl(NHCH(2)CMe(2))(C(6)H(4)CHMe(2)NMe(2)-C,N)Pd] (1a). The reaction of the
      aziridine complex trans-[Cl(2)Pd(HNC(2)H(4))(2)] with an excess of aziridine in
      the presence of AgOTf gave the ionic chelate complex trans
      [(C(2)H(4)NC(2)H(4)NH(2)-N,N')(2)Pd](OTf)(2) (2b) which contains the new ligand b
      formed by an unexpected insertion and ring opening reaction of two aziridines
      ("aziridine dimerization"). CuCl(2) reacted in pure HNC(2)H(4) or HNCH(2)CMe(2)
      (b) again by "dimerization" to give the tris-chelated ionic complex
      [Cu(C(2)H(4)NC(2)H(4)NH(2)-N,N')(3)]Cl(2) (3b) or the bis-chelated complex
      [CuCl(C(2)H(2)Me(2)NC(2)H(2)Me(2)NH(2)-N,N')(2)]Cl (4c). By addition of 2H-3
      phenylazirine (d) to PdCl(2), trans-[Cl(2)Pd(NCH(2)CPh)(2)] (5d) was formed. All
      new compounds were characterized by NMR, IR and mass spectra and also by X-ray
      structure analyses (except 3b). Additionally the cytotoxic effects of these
      complexes were examined on HL-60 and NALM-6 human leukemia cells and melanoma WM
      115 cells. The antimicrobial activity was also determined. The growth of Gram
      positive bacterial strains (S. aureus, S. epidermidis, E. faecalis) was inhibited
      by almost all tested complexes at the concentrations of 37.5-300.0 MUg mL(-1).
      However, MIC values of complexes obtained for Gram-negative E. coli and P.
      aeruginosa, as well as for C. albicans yeast, mostly exceeded 300 MUg mL(-1). The
      highest antibacterial activity was achieved by complexes 1a and 2b. Complex 2b
      also inhibited the growth of Gram-negative bacteria.

PMID- 22466758
TI  - Overexpression of ZEB1 associated with metastasis and invasion in patients with
      gastric carcinoma.
AB  - The aim of this study was to investigate the expression of ZEB1 in gastric
      carcinoma, its correlation with the clinicopathology of gastric carcinoma, and
      the role of ZEB1 in invasion and metastasis in gastric carcinoma. ZEB1 expression
      was analyzed by immunohistochemistry and Western blot in 45 gastric carcinoma
      tissue samples that contained the adjacent gastric mucosa. The correlation
      between ZEB1 expression, the occurrence and development of gastric cancer, and
      clinical pathology was investigated. ZEB1 expression in the human gastric
      carcinoma cell line AGS was downregulated by RNA interference, and changes in
      ZEB1 expression corresponded with changes in the invasive and metastatic ability
      of AGS cells. Immunohistochemistry revealed that ZEB1 protein expression in
      gastric carcinoma tissues was significantly higher than in normal gastric mucosa
      tissues (p < 0.001). A lower degree of differentiation of gastric cancer (p =
      0.009), a higher TNM (tumor, node, and metastasis) stage (p = 0.010), and a
      larger scope of invasion were correlated with higher expression of ZEB1 (p =
      0.041, 0.002). However, the expression of ZEB1 in gastric carcinoma tissue was
      independent of gender, age, and tumor size (p > 0.05). Western blot results also
      showed that ZEB1 protein expression was significantly higher in gastric carcinoma
      tissue than in the adjacent normal gastric mucosa tissue (p = 0.008). A lower
      degree of differentiation of the gastric carcinoma correlated with a higher TNM
      stage, and a larger scope of invasion correlated with increased ZEB1 expression
      (p = 0.023). Transfection of ZEB1 siRNA in AGS cells significantly decreased the
      expression level of ZEB1 protein (p = 0.035). Furthermore, the number of cells
      that could pass through the Transwell chamber was significantly lower in the
      transfected group than in the non-transfected control group (p = 0.039),
      indicating that the suppression of ZEB1 expression could significantly reduce the
      invasive and metastatic ability of AGS cells (p = 0.005). Concluding, in gastric
      carcinoma tissue, overexpression of ZEB1 may be related to the occurrence and
      development as well as invasion and metastasis of gastric carcinoma.

PMID- 22466759
TI  - Mitral valve with three orifices after percutaneous repair with the MitraClip
      system: the triple-orifice technique.

PMID- 22466760
TI  - [Preoperative alpha-adrenoceptor block in asymptomatic pheochromocytoma? Pro].
AB  - In approximately 90% of all cases a pheochromocytoma causes sustained or
      paroxysmal hypertension. During surgical resection tumor manipulation can lead to
      excessive catecholamine release with the risk of life-threatening complications.
      Since the early 1950s a preoperative medical treatment with an alpha-adrenoceptor
      blocking agent has been successfully administered for prevention of hemodynamic
      instability but not all pheochromocytomas are associated with hypertension.
      Currently the discovery of asymptomatic pheochromocytomas is more frequent than
      in the time prior to modern imaging techniques (computed tomography, magnetic
      resonance imaging). There is little information about this type of
      pheochromocytoma in the literature. This article discusses the question if
      preoperative alpha-adrenoceptor block is also indicated in asymptomatic
      pheochromocytomas based on the current literature.

PMID- 22466761
TI  - [Analysis and design structure of an aging society].
AB  - AIM: On observing present Japanese society, we can find deep gaps between the
      present system and its probable future. One of the gaps may be due to the
      misconception that future societal make up is not definite. The aim of the
      current study was to investigate a future societal structure and to develop
      methods of adding a timed dimension policy to the societal structure. This is
      named "A theory of structuralism economics". METHODS: We developed 3 societal
      structure projection engines and applied a system of dynamics language to
      estimate the future total population of Japan. RESULTS: The Japan total
      population reached a maximum in 2005, and thereafter depopulation begun. The
      populations in the younger working age group (from 25 to 54 years old) and those
      in the elderly working age group (from 55 to 84 years old) became almost equal in
      2010. As economic growth rate depends upon an increase in the working population,
      the increase in national income rate of Japan approached over 10% per year
      between 1950 to 1970. The increased working age population of the same period
      exceeded 2.5% annually. However, after 2005 depopulation began in Japan. In
      future, national income will decrease proportional to the working age population,
      but personal national income will hold almost unchanged. CONCLUSION: We propose a
      new strategy for future society structure. The working age should be extended by
      10 years. Labor power will come to exceed 60% of the population and will
      thereafter become stable.

PMID- 22466762
TI  - [Expectations toward the care service and the medical service for elderly in
      Japan].
AB  - AIM: With the purpose of gathering basic data in order to prompte various
      research toward the realization of a vibrant aging society, we performed a
      nationwide 'Survey on life' intended for citizens over 60 years old who engage in
      independent living, preserving their state of health even after retirement.
      METHODS: We created a survey form consisting of 14 question items. Processing
      4,000 persons surveyed from 100 locations chosen nationwide, we obtained a total
      of 2,370 answers from both male and female subjects, with an effective recovery
      rate of 59.3%. We divided the respondents according to their age into four groups
      (group 1: 60-64 years; group 2: 65-69 years; group 3: 70-74 years; group 4: over
      75 years), examined and analyzed them using multivariate statistical analysis
      followed by a summary of each response item. RESULTS: In the main aggregate
      results, the percentage living with a spouse indicated a double decrease in the
      4th group of female respondents in comparison with male respondents, and together
      with that an increase of the living alone percentage identical with the one above
      could be seen. The subjective sense of health has gradually declined after
      peaking in group 1, while the number of persons complaining of poor health
      doubled as we moved to group 3 and group 4. Analysis of the factors that
      contribute to discrimination in each age category showed that health and economic
      items together with social participation items were extracted as the main
      determining factors. Economic anxiety is strong in group 1 and group 2, in
      particular, anxiety about the future life showed a tendency about two times
      higher in the female group rather than the male group of the same age category.
      The eagerness to contribute to society indicated a high tendency within the
      female group 1 and group 2. In the canonical correlation analysis of all age
      categories, the weight coefficient of physical anxiety and health anxiety within
      the male groups showed 1.95, respectively 2.52. On the other hand, economic
      anxiety and anxiety about future life indicated -1.97, respectively -1.70,
      showing large fluctuations on these four items. The female groups presented the
      same tendency. Items showing a high correlation with individual respondents,
      showed an increase of the wieght coefficients, starting with younger age, in the
      following order: 'state of health', 'mental and physical energy', 'desire to
      contribute to society', 'state of sleep', 'leasure activity', 'living with
      family', 'health anxiety', 'physical anxiety'. There was no distinction between
      male and female. Observing the aspects of the relative changes represented in the
      graphic in the order of the age category, searching for the avarage value of the
      weight coefficient of all individual respondents considering the four items that
      registered high fluctuations, within group 1 and group 2 under 70 years, the
      economic anxiety and anxiety about future life are strong, so that as we move to
      groups over 70 years, health and physical anxieties tend to emerge slowly.
      CONCLUSIONS: The result of this survey suggested that for senior citizens,
      through all age categories, economic and health anxieties existing at various
      levels and under different aspects, will soon bring a large strain upon the mind
      of the elderly, turning into the main negative background factor which leads to a
      general decline of the mental health and the body, and what is more, the
      willingness to be active.

PMID- 22466763
TI  - [Health promotion for the elderly living in the community based on action
      research].

PMID- 22466764
TI  - [Longevity society and bio-gerontology].

PMID- 22466765
TI  - [Contribution of oral functions to maintenance and promotion of health].

PMID- 22466766
TI  - [For the safety of aged society--a role of the Japanese Association of
      Psychogeriatrics].

PMID- 22466767
TI  - [Life stability and care management of the elderly].

PMID- 22466768
TI  - [Brief history and practical problems of the prevention of long-term care state].

PMID- 22466770
TI  - [Frailty and fall prevention].

PMID- 22466769
TI  - [Critical appraisal of preventive care--from the perspective of health economics
      and policy].
AB  - I examined the effects and problems of preventive care (the New Preventive
      Benefit) that was introduced to Japan's public long-term care insurance system in
      2006, reviewing official publications of the Ministry of Health, Labor and
      Welfare and Japanese government as well as Japanese and English empirical studies
      on preventive care, using five pillars as follows. Firstly, I briefly introduced
      my previous literature review of preventive care in 2006. Secondly, I show five
      important points and pitfalls concerning economic evaluation of health services.
      Thirdly, I reviewed Japanese articles and publications that analyzed economic
      effect of preventive care. Fourthly, I reviewed English review articles on the
      effect of fall-prevention programs that are most widely analyzed among several
      preventive care. Finally, I showed that the Ministry of Health, Labor and Wealth
      "deflated" the estimation of cost that can be incurred by preventive care in 5
      years (from 2006 to 2011). Based on these analyses, there is not yet solid
      evidence that preventive care can decrease the total cost of long-term care.

PMID- 22466771
TI  - [Prevention of cognitive decline].

PMID- 22466772
TI  - [Ten year retrospection after the position statement 2001 for terminal care in
      the elderly by Japan Geriatrics Society].

PMID- 22466773
TI  - [Cognition in the end of life care for the older people: perspective of directors
      in the Japan Geriatrics Society].

PMID- 22466774
TI  - [Survey of Japanese geriatricians on their practices and attitude towards
      artificial nutrition and hydration for patients with end-stage dementia].

PMID- 22466775
TI  - [Study on the present status of the Position Statement by the Japan Geriatrics
      Society about terminal medicine and care for the elderly].

PMID- 22466776
TI  - [A revised proposal for "Position Statement from the Japan Geriatrics Society:
      the Terminal Care of the Elderly"].

PMID- 22466777
TI  - [Factors associated with mental health well-being of urban community-dwelling
      elders in Japan: comparison between subjects with and without long-term care
      insurance certification].
AB  - AIM: The present study aimed to (1) examine the mental health well-being of urban
      community-dwelling elderly individuals; and (2) examine factors related to mental
      health well-being of those with long-term care insurance certification (LTCI+)
      and those without LTCI certification (LTCI-). METHODS: We conducted a community
      based, cross-sectional study that included 3,905 subjects aged 65 years or older
      living in Tokyo, Japan. A self-administered questionnaire was mailed to each
      participant. Mental health well-being was assessed using the Japanese version of
      the World Health Organization Mental Health Wellbeing Index--five items (WHO-5).
      RESULTS: Of the 2,431 respondents (response rate, 63.5%), 1,954 who completed WHO
      5 were analyzed (241 LTCI+; 1,713 LTCI-). The total score of WHO-5 was 15.61+/
      6.08 among all subjects; when a cut-off criterion of 12/13 was used, the
      frequency of low mental health well-being was 29.5% among all subjects. In a
      stratified analysis according to LTCI certification using multivariate logistic
      regression analysis, small social support network, heart disease, and daytime
      sleepiness were independently associated with low mental health well-being for
      the LTCI+ group; low education level, small social support network, low
      subjective health, daytime sleepiness, and worries about forgetfulness were
      independently associated with low mental health well-being for the LTCI- group.
      CONCLUSION: To improve mental health well-being of community-dwelling elderly
      individuals with LTCI certification, attention should be focused on those with
      small social network or daytime sleepiness. To improve mental health well-being
      of community-dwelling elderly individuals without LTCI certification, attention
      should be focused on those with small social network, low subjective health, or
      worries about forgetfulness.

PMID- 22466778
TI  - [Oral conditions and oral management approaches in mild dementia patients].
AB  - AIM: The oral management of dementia patients is critical to prevent aspiration
      pneumonia and maintain patients' quality of life. However, the oral health status
      of these patients has not been adequately elucidated thus far, and it is not well
      understood how oral care is managed for mild dementia patients. To provide
      effective oral management for mild dementia patients, we investigated their oral
      health status and how their oral care was managed. METHODS: We enrolled 10
      outpatients aged 66 to 85 years old who regularly visited our neurology clinic.
      All of the patients had mild dementia. We conducted 2 questionnaire studies
      regarding oral hygiene and dentures and performed an oral examination to evaluate
      the changes in oral hygiene status over time. The questionnaire was designed to
      explore the understanding of oral hygiene methods. Oral care instructions were
      given to the patients and their caregivers. Three surveys of 2 questionnaires
      each were performed. The survey was conducted at the initial visit, and 3 months
      and 6 months later. RESULTS: Although oral care instructions were given to the
      patients and their caregivers, neither their plaque index nor gingival index
      showed major improvement over time. Based on the results of these questionnaires,
      patient awareness of oral hygiene did not change over time. CONCLUSION: It is
      difficult for patients with mild dementia to perform oral care by themselves. It
      is important to make oral hygiene habits second nature in middle-aged patients,
      to introduce oral management to be performed by the caregivers and to promote
      early dental intervention to improve and maintain oral hygiene status in mild
      dementia patients.

PMID- 22466779
TI  - [Investigation of pain assessment trends among residents in Japanese long-term
      care facilities].
AB  - AIM: Pain management is vital for both the maintenance and improvement of the
      quality of life of residents, in Japanese long-term care facilities. However, few
      studies examining pain assessment in older populations have been published. The
      purpose of this study is to investigate the actual conditions related to pain
      assessment of residents by nurses in Japanese long-term care facilities. Included
      in this investigation are the actual frequency of pain assessments, the nurses
      own perceptions of the pain assessment of their residents, whether or not nurses
      have undertaken any training related to pain assessment, and the need for a pain
      assessment training period. METHODS: A questionnaire was distributed to 487
      nurses in 60 Japanese long-term care facilities. RESULTS: A total of 443 valid
      responses were collected. The data revealed that 74.7% of these nurses lack the
      confidence to suitably assess the residents' pain and 44.2% of these nurses do
      not conduct pain assessments on a regular basis. Additionally, only 9.9% of the
      nurses surveyed have participated in seminars concerning pain in older people.
      CONCLUSION: The results indicate that over 70% of nurses lack the confidence to
      suitably assess their residents' pain. In addition, the number of residents who
      cannot self-report their pain because of cognitive impairment is increasing.
      Therefore, it is necessary to develop new approaches which provide nurses with
      sufficient knowledge and confidence to conduct appropriate pain assessments on
      their residents.

PMID- 22466780
TI  - [Effect of intermittent rehydration therapy as an oral and enteral rehydration
      solution, alone or in combination with intravenous administration on
      intravascular dehydration].
AB  - AIM: The purpose of this study was to demonstrate the effectiveness of
      intermittent fluid infusion (intermittent rehydration therapy) to dehydrated
      elderly patients and the efficacy of Heisei Solution Water (HSW), an oral and
      enteral rehydration solution developed by our group. METHODS: We enrolled 375
      elderly patients with suspected dehydration from among 1,921 patients of our
      hospital and 13 affiliated hospitals. A total of 36 of 375 patients received
      intermittent rehydration therapy. These patients were then divided into 3 groups
      according to the method of administration: (1) oral and enteral administration
      (n=16), (2) intravenous administration only (n=10) and (3) combined oral, enteral
      and intravenous administration (n=10). We then compared blood urea
      nitrogen/creatinine (BUN/Cr) ratios among the 3 groups. RESULTS: BUN/Cr ratios
      were improved in all groups, but there was no statistically significant
      difference in the degree of improvement of BUN/Cr ratios among the 3 groups.
      CONCLUSION: Intermittent rehydration therapy is a highly effective way to manage
      dehydration. The intermittent oral and enteral administration of HSW demonstrated
      the same effectiveness as other forms of administration.

PMID- 22466781
TI  - [Diaper cystitis as recurrent cause of urinary infections in geriatric community
      hospital].
AB  - AIM: Chronic cystitis in diaper-dependent elderly patients can be a causative
      pathology for recurrent urinary tract infections (UTIs) in community hospitals.
      METHODS: We analyzed hospital infections to determine causative organisms from
      January 2007 to December 2009 in patients in a long-term care hospital. The
      reading causes of hospital infections were UTIs (30.4%), aspiration pneumonia
      (CAP; 26%) and hospital-acquired pneumonia (HAP; 17.2%). Of a total of 3,097
      hospital infections over the investigation period, UTIs were the most common
      (n=940, 30.4%) followed by CAP (n=809, 26%) and HAP (n=533, 17.2%). Of 278 UTIs
      in 2007, the causative strains were Escherichia coli (n=106, 38%), Enterococcus
      faecalis (n=44, 16%), Proteus mirabilis (n=31, 11%), alpha-hemolytic
      streptococcus (n=22, 8%), and beta-hemolytic streptococcus (n=14, 5%). Extended
      spectrum beta-lactamase (n=14, 13%) strains were noted in 106 patients with
      Escherichia coli. We then retrospectively examined the records of 110 diaper
      dependent elderly patients, (medical words, n=52, mix-care wards, n=68) for UTIs
      over the same study period. Of these 16 (14.5%) had no UTIs at any time, 12 (11%)
      were infected 50% of the time, 17 (15.5%) were infected 51% to 99% of the time
      and 65 (59%) were infected 100% of the time. The UTI rate was not correlated with
      bladder function or between the 2 wards. We treated bacterial cystitis with
      antibiotics for 3-5 days but these were unsuccessful. Antiseptics worked
      temporarily, but recurrence or re-infection always occurred. It remains unknown
      if diapers are a potential cause of chronic cystitis in dependent elderly
      patients. The clinical dilemma of whether recurrent diaper cystitis should be
      treated and prohibit the growth and spread of drug-resistant strains, remains
      challenging.

PMID- 22466783
TI  - [Scheme for elder abuse prevention in the community].

PMID- 22466782
TI  - [86-aged case of Alzheimer disease followed by nursing home after percutaneous
      endoscopic gastrostomy].

PMID- 22466784
TI  - Replica exchange Monte-Carlo simulations of helix bundle membrane proteins:
      rotational parameters of helices.
AB  - We propose a united-residue model of membrane proteins to investigate the
      structures of helix bundle membrane proteins (HBMPs) using coarse-grained (CG)
      replica exchange Monte-Carlo (REMC) simulations. To demonstrate the method, it is
      used to identify the ground state of HBMPs in a CG model, including
      bacteriorhodopsin (BR), halorhodopsin (HR), and their subdomains. The rotational
      parameters of transmembrane helices (TMHs) are extracted directly from the
      simulations, which can be compared with their experimental measurements from site
      directed dichroism. In particular, the effects of amphiphilic interaction among
      the surfaces of TMHs on the rotational angles of helices are discussed. The
      proposed CG model gives a reasonably good structure prediction of HBMPs, as well
      as a clear physical picture for the packing, tilting, orientation, and rotation
      of TMHs. The root mean square deviation (RMSD) in coordinates of C(alpha) atoms
      of the ground state CG structure from the X-ray structure is 5.03 A for BR and
      6.70 A for HR. The final structure of HBMPs is obtained from the all-atom
      molecular dynamics simulations by refining the predicted CG structure, whose RMSD
      is 4.38 A for BR and 5.70 A for HR.

PMID- 22466785
TI  - Reaction of a copper(II)-nitrosyl complex with hydrogen peroxide: putative
      formation of a copper(I)-peroxynitrite intermediate.
AB  - The reaction of a Cu(II)-nitrosyl complex (1) with hydrogen peroxide at -20 
      degrees C in acetonitrile results in the formation of the corresponding Cu(I)
      peroxynitrite intermediate. The reduction of the Cu(II) center was monitored by
      UV-visible spectroscopic studies. Formation of the peroxynitrite intermediate has
      been confirmed by its characteristic phenol ring nitration reaction as well as
      isolation of corresponding Cu(I)-nitrate (2). On air oxidation, 2 resulted in the
      corresponding Cu(II)-nitrate (3). Thus, these results demonstrate a possible
      decomposition pathway for H(2)O(2) and NO through the formation of a
      peroxynitrite intermediate in biological systems.

PMID- 22466786
TI  - The reduction of allograft arteriosclerosis in intestinal transplant is
      associated with sphingosine kinase 1/sphingosine-1-phosphate signaling after fish
      oil treatment.
AB  - BACKGROUND: Transplant arteriosclerosis is a major cause of late intestinal
      allograft dysfunction. However, little is known about the immunologic and
      molecular mechanisms underlying it, and no effective treatment is available. This
      study aimed to investigate the role of sphingosine kinase 1 (SPHK1)/sphingosine-1
      phosphate (S1P) in transplant arteriosclerosis and find out whether fish oil (FO)
      attenuates allograft arteriosclerosis through S1P signaling. METHODS: A rat model
      with orthotopic intestinal transplantation was conducted in this study. Animals
      received daily FO supplementation after intestinal transplant. The allogeneic
      recipients by phosphate-buffered saline or corn oil treatment served as controls.
      The allograft arteriosclerosis was characterized, and the expression of SPHK1 and
      S1P receptors (S1P1, S1P2, and S1P3) was determined on day 190 posttransplant.
      RESULTS: The allogeneic controls presented transplant vasculopathy in mesenteric
      vessels, including intimal thickening, fibrosis, and leukocyte infiltration. The
      transplant arteriosclerosis was markedly reduced in FO-fed animals. The pression
      of SPHK1 and its activity were significantly augmented, and the expression of
      S1P1 and S1P3 messenger RNA was up-regulated in the allogeneic controls. FO
      supplementation suppressed the activation of SPHK1 and led to a decrease in the
      expression of S1P1 and S1P3 in these tissues in transplant arteriosclerosis.
      CONCLUSIONS: These results demonstrate that the activation of SPHK1/S1P signaling
      plays a possible role in the pathogenesis of transplant arteriosclerosis. The
      reduction of allograft arteriosclerosis by FO may be associated with down
      regulation of SPHK1/S1P signaling. Understanding the role of FO for SPHK1/S1P may
      help us to identify considerable therapeutic targets for transplant
      arteriosclerosis.

PMID- 22466787
TI  - Enhancement of liver regeneration by adenosine triphosphate-sensitive K+ channel
      opener (diazoxide) after partial hepatectomy.
AB  - BACKGROUND: Enhancement of liver regeneration is a matter of importance after
      partial liver transplantation including small-for-size grafting. Mitochondrial
      adenosine triphosphate (ATP)-sensitive K+ (mitoKATP) channel plays an important
      role in mitochondrial bioenergetics, which is a prerequisite for liver
      regeneration. However, the ATP-sensitive K+ (KATP) channel in hepatocytes is
      incompletely understood. We investigated the KATP channel in hepatocytes and
      examined the effects of diazoxide, a potent KATP channel opener, on liver
      regeneration using a rat model. METHODS: Using rat primary hepatocytes,
      expression and localization of KATP channel subunits, Kir6.x and sulfonylurea
      receptor (SUR)x, were studied by polymerase chain reaction, Western blotting, and
      immunostaining. To investigate the role of KATP channel openers in liver
      regeneration, we allocated rats into four groups: control (vehicle) (n=24),
      diazoxide (n=24), vehicle plus channel blocker (n=6), and diazoxide plus channel
      blocker (n=6) groups. After 70% partial hepatectomy, hepatic tissue ATP levels,
      liver-to-body weight ratio, and proliferation rate of hepatocytes were examined.
      RESULTS: KATP channel subunits, Kir6.1 and SUR1, were detected on hepatic
      mitochondria. During liver regeneration, liver-to-body weight ratio,
      proliferation rate of hepatocytes, and the hepatic ATP level were significantly
      higher in the diazoxide group than the control group at 2 days after partial
      hepatectomy. These effects of diazoxide were neutralized by a KATP channel
      blocker. CONCLUSIONS: We demonstrated the existence of a mitoKATP channel in
      hepatocytes composed of Kir6.1 and SUR1. Diazoxide could enhance liver
      regeneration by keeping a higher ATP content of the liver tissue. These results
      suggest that diazoxide will sustain the mitochondrial energetics through the
      mitoKATP channel opening.

PMID- 22466788
TI  - Pushing the limits in live kidney donation:  can you ever be too old or too heavy
      to donate?

PMID- 22466789
TI  - Female genital chronic graft-versus-host disease: importance of early diagnosis
      to avoid severe complications.
AB  - BACKGROUND: Genital chronic graft-versus-host disease (GVHD) is a frequent but
      underdiagnosed complication of allogeneic stem-cell transplantation impairing
      quality of life. METHODS: We identified 32 female patients with genital chronic
      GVHD (cGVHD) who underwent allogeneic hematopoietic stem-cell transplantation in
      our center between 2000 and 2010 and who were followed after transplantation in a
      specialized gynecological consultation. Pre- and posttransplantation clinical
      data and detailed acute and cGVHD data were collected. All patients received the
      same local treatment for genital lesions. RESULTS: At presentation, most patients
      complained about vaginal dryness and dyspareunia with impairment in sexual
      activity. Fifty percent of patients had grade I genital lesions and 50% had grade
      II or III lesions. Patients seen later in gynecological consultation had more
      severe lesions than patients seen early after transplantation. At the time of
      diagnosis, most patients had other cutaneous or mucous localizations of cGVHD. In
      most cases, lesions were stabilized or decreased with local steroids and estrogen
      treatment, and most patients could resume sexual activity. Treatment was more
      efficient in patients with mild lesions than in others. CONCLUSIONS: Genital
      cGVHD should be systematically searched for in women who have received allogeneic
      hematopoietic stem-cell transplantation in an early specialized consultation,
      especially in case of other cutaneous or mucous localizations of cGVHD. Local
      treatment associating steroids and estrogen seemed to prevent further evolution
      of grade I genital lesions and to avoid surgical treatment.

PMID- 22466790
TI  - Posttransplant major histocompatibility complex class I chain-related gene A
      antibodies and long-term graft outcomes in a multicenter cohort of 779 kidney
      transplant recipients.
AB  - BACKGROUND: The impact of major histocompatibility class I chain-related A (MICA)
      antibodies on renal graft outcomes is unclear. The goal of this work was to
      assess the impact of posttransplant MICA antibodies, assayed at 1 year, with two
      commercially available kits, on long-term renal graft outcomes. METHODS: We
      retrospectively tested sera from 779 kidney transplant recipients with two single
      antigen flow bead assays 1 year after transplantation. Samples were considered
      positive for MICA if they were positive in both tests or positive for MICA
      specificities that were present in one kit only. The main outcome was 4-year
      death-censored graft survival. RESULTS: The prevalence of MICA antibodies was
      5.4% at 1 year. MICA+ patients were more frequently human leukocyte antigen (HLA)
      sensitized and regrafted. Four-year death-censored graft survival was not
      different between MICA+ and MICA- patients (97% vs. 94%, P=0.28). By Cox
      multivariate analysis, independent risk factors for graft loss were as follows:
      number of HLA DR mismatches, acute rejection within the first year
      posttransplantation, 1-year serum creatinine, and the presence of HLA antibodies
      at 1 year, but not the presence of MICA antibodies. CONCLUSIONS: These data do
      not support an independent pathogenic role for MICA in long-term renal graft
      injury and question the interest of posttransplant monitoring of MICA antibodies
      with single-antigen flow bead assays currently available.

PMID- 22466791
TI  - Energy cost of walking and its association with gait parameters, daily activity,
      and fatigue in persons with mild multiple sclerosis.
AB  - BACKGROUND: Energy cost of walking (C(w)) is elevated in persons with multiple
      sclerosis (MS), perhaps because of gait impairment, and may impact daily activity
      and fatigue. OBJECTIVE: The authors examined for associations between C(w),
      spatiotemporal gait parameters, daily activity, and perceived fatigue in persons
      with mild MS. METHODS: Forty-four participants completed 4 trials of walking on a
      GAITRite mat and one 6-minute trial of walking on a treadmill at a constant,
      controlled speed of 54 m min(-1) while expired gases were analyzed for oxygen
      consumption. Participants also completed the Fatigue Severity Scale (FSS) and
      wore a waist-mounted accelerometer for 7 days. RESULTS: C (w) was significantly
      and inversely associated with gait speed (r = -.25) and stride length (r = -.32)
      and positively associated with double limb support (r = .27). C (w) was
      significantly and inversely associated with daily accelerometer activity counts
      (r = -.35) and positively associated with FSS scores (rho = .31). CONCLUSION: The
      results support the development and application of rehabilitation strategies to
      address impaired gait parameters as an approach to improve C(w), daily
      activities, and fatigue.

PMID- 22466793
TI  - Integrated genetic and computation methods for in planta cytometry.
AB  - We present the coupled use of specifically localized fluorescent gene markers and
      image processing for automated quantitative analysis of cell growth and genetic
      activity across living plant tissues. We used fluorescent protein markers to
      identify cells, create seeds and boundaries for the automatic segmentation of
      cell geometries and ratiometrically measure gene expression cell by cell in
      Arabidopsis thaliana.

PMID- 22466792
TI  - Getting neurorehabilitation right: what can be learned from animal models?
AB  - Animal models suggest that a month of heightened plasticity occurs in the brain
      after stroke, accompanied by most of the recovery from impairment. This period of
      peri-infarct and remote plasticity is associated with changes in
      excitatory/inhibitory balance and the spatial extent and activation of cortical
      maps and structural remodeling. The best time for experience and training to
      improve outcome is unclear. In animal models, very early (<5 days from onset) and
      intense training may lead to increased histological damage. Conversely, late
      rehabilitation (>30 days) is much less effective both in terms of outcome and
      morphological changes associated with plasticity. In clinical practice,
      rehabilitation after disabling stroke involves a relatively brief period of
      inpatient therapy that does not come close to matching intensity levels
      investigated in animal models and includes the training of compensatory
      strategies that have minimal impact on impairment. Current rehabilitation
      treatments have a disappointingly modest effect on impairment early or late after
      stroke. Translation from animal models will require the following: (1)
      substantial increases in the intensity and dosage of treatments offered in the
      first month after stroke with an emphasis on impairment; (2) combinational
      approaches such as noninvasive brain stimulation with robotics, based on current
      understanding of motor learning and brain plasticity; and (3) research that
      emphasizes mechanistic phase II studies over premature phase III clinical trials.

PMID- 22466794
TI  - Direct visualization of specifically modified extracellular glycans in living
      animals.
AB  - Modification patterns of heparan sulfate coordinate protein function in
      metazoans, yet in vivo imaging of such non-genetically encoded structures has
      been impossible. Here we report a transgenic method in Caenorhabditis elegans
      that allows direct live imaging of specific heparan sulfate modification
      patterns. This experimental approach reveals a dynamic and cell-specific heparan
      sulfate landscape and could in principle be adapted to visualize and analyze any
      extracellular molecule in vivo.

PMID- 22466795
TI  - Quantitative fluorescence labeling of aldehyde-tagged proteins for single
      molecule imaging.
AB  - A major hurdle for molecular mechanistic studies of many proteins is the lack of
      a general method for fluorescence labeling with high efficiency, specificity and
      speed. By incorporating an aldehyde motif genetically into a protein and
      improving the labeling kinetics substantially under mild conditions, we achieved
      fast, site-specific labeling of a protein with ~100% efficiency while maintaining
      the biological function. We show that an aldehyde-tagged protein can be
      specifically labeled in cell extracts without protein purification and then can
      be used in single-molecule pull-down analysis. We also show the unique power of
      our method in single-molecule studies on the transient interactions and switching
      between two quantitatively labeled DNA polymerases on their processivity factor.

PMID- 22466796
TI  - Gender differences and regionalization of the cultural significance of wild
      mushrooms around La Malinche volcano, Tlaxcala, Mexico.
AB  - The purpose of this study was to determine the cultural significance of wild
      mushrooms in 10 communities on the slopes of La Malinche volcano, Tlaxcala. The
      frequency and order of mention of each mushroom species in interviews of 200
      individuals were used as indicators of the relative cultural significance of each
      species. A X(2) analysis was used to compare the frequency of mention of each
      species between males and females, and a Mann-Whitney U test was used to compare
      the difference in the total number of fungi mentioned by either gender.
      Traditional names for mushroom species were documented and frequency of mention
      assessed through multivariate statistics. The fungi with highest frequency of
      mention were Amanita basii, Lyophyllum decastes, Boletus pinophilus, Gomphus
      floccosus and Cantharellus cibarius complex. We found significant differences in
      the frequency of mention of different fungi by males and females but no
      significant difference was found for the total number of fungi mentioned by
      either gender. Principal component analysis suggested a cultural regionalization
      of La Malinche volcano communities based on preferences for consumption and use
      of traditional names. We observed two groups: one formed by communities on the
      eastern part of the volcano (with mixed cultures) and the other including
      communities on the western slope (ethnic Nahua towns). San Isidro Buensuceso is
      the most distinct community, according to the criteria in this study.

PMID- 22466797
TI  - Fomitiporia cupressicola sp. nov., a parasite on Cupressus arizonica, and
      additional unnamed clades in the southern USA and northern Mexico, determined by
      multilocus phylogenetic analyses.
AB  - Fomitiporia cupressicola sp. nov., found in living Cupressus arizonica, is
      described on the basis of several collections originating from a high altitude
      forest in the northern Sierra Madre Occidental, Mexico. The species forms a
      monophyletic clade, basal to a larger lineage comprising species originating
      mainly from temperate to Mediterranean areas of the northern hemisphere. The
      phylogenetic approach in Fomitiporia also revealed multiple unnamed clades within
      the F. robusta complex in the southern USA and northern Mexico, representing
      potential species. The status of the F. robusta complex in North America is
      discussed briefly.

PMID- 22466798
TI  - Elucidating the role of the phenylacetic acid metabolic complex in the pathogenic
      activity of Rhizoctonia solani anastomosis group 3.
AB  - The soil fungus Rhizoctonia solani produces phytotoxic phenylacetic acid (PAA)
      and hydroxy (OH-) and methoxy (MeO-) derivatives of PAA. However, limited
      information is available on the specific role that these compounds play in the
      development of Rhizoctonia disease symptoms and concentration(s) required to
      induce a host response. Reports that PAA inhibits the growth of R. solani
      conflict with the established ability of the fungus to produce and metabolize
      PAA. Experiments were conducted to clarify the role of the PAA metabolic complex
      in Rhizoctonia disease. In this study the concentration of PAA and derivatives
      required to induce tomato root necrosis and stem canker, in the absence of the
      fungus, and the concentration that inhibits mycelial growth of R. solani were
      determined. The effect of exogenous PAA and derivatives of PAA on tomato seedling
      growth also was investigated. Growth of tomato seedlings in medium containing 0.1
      7.5 mM PAA and derivatives induced necrosis of up to 85% of root system. Canker
      development resulted from injection of tomato seedling stems with 7.5 mM PAA, 3
      OH-PAA, or 3-MeO-PAA. PAA in the growth medium reduced R. solani biomass, with
      50% reduction observed at 7.5 mM. PAA, and derivatives were quantified from the
      culture medium of 14 isolates of R. solani belonging to three distinct
      anastomosis groups by GC-MS. The quantities ranged from below the limit of
      detection to 678 nM, below the concentrations experimentally determined to be
      phytotoxic. Correlation analyses revealed that isolates of R. solani that
      produced high PAA and derivatives in vitro also caused high mortality on tomato
      seedlings. The results of this investigation add to the body of evidence that the
      PAA metabolic complex is involved in Rhizoctonia disease development but do not
      indicate that production of these compounds is the primary or the only
      determinant of pathogenicity.

PMID- 22466800
TI  - Rab11 rescues synaptic dysfunction and behavioural deficits in a Drosophila model
      of Huntington's disease.
AB  - Synapse abnormalities in Huntington's disease (HD) patients can precede clinical
      diagnosis and neuron loss by decades. The polyglutamine expansion in the
      huntingtin (htt) protein that underlies this disorder leads to perturbations in
      many cellular pathways, including the disruption of Rab11-dependent endosomal
      recycling. Impairment of the small GTPase Rab11 leads to the defective formation
      of vesicles in HD models and may thus contribute to the early stages of the
      synaptic dysfunction in this disorder. Here, we employ transgenic Drosophila
      melanogaster models of HD to investigate anomalies at the synapse and the role of
      Rab11 in this pathology. We find that the expression of mutant htt in the larval
      neuromuscular junction decreases the presynaptic vesicle size, reduces quantal
      amplitudes and evoked synaptic transmission and alters larval crawling behaviour.
      Furthermore, these indicators of early synaptic dysfunction are reversed by the
      overexpression of Rab11. This work highlights a potential novel HD therapeutic
      strategy for early intervention, prior to neuronal loss and clinical
      manifestation of disease.

PMID- 22466804
TI  - Estimating central systolic blood pressure during oscillometric determination of
      blood pressure:  proof of concept and validation by comparison with intra-aortic
      pressure recording and arterial tonometry.
AB  - OBJECTIVES: Central systolic blood pressure is usually estimated by
      transformation of a peripheral arterial waveform obtained by tonometry and
      calibrated from conventional measurements of brachial artery blood pressure from
      a brachial cuff using the oscillometric principle. We investigated whether
      central blood pressure could be obtained directly from a brachial cuff waveform,
      allowing the measurement of central blood pressure to be incorporated into the
      standard oscillometric determination of blood pressure. METHODS: Values of
      central systolic blood pressure obtained from a brachial cuff waveform were
      compared with those obtained using a pressure-tipped intra-aortic catheter in 29
      individuals undergoing cardiac catheterization. To remove errors introduced by
      the measurement of peripheral blood pressure, transformed brachial waveforms were
      calibrated using values of mean and diastolic pressure from the intra-aortic
      catheter. In a second study, the values obtained from the brachial cuff were
      compared with those obtained using a noninvasive tonometric method using
      calibration from mean and diastolic and from systolic and diastolic blood
      pressure derived from a standard oscillometric algorithm in 100 individuals (46
      women, 19-81 years) with blood pressure ranging from 89/52 to 230/117 mmHg.
      RESULTS: In study 1, the mean difference +/- SD of brachial cuff-derived values
      and intra-aortic values was 0.0 +/- 5.9 mmHg. In study 2, the mean difference for
      brachial cuff-derived values and tonometer values was -0.6 +/- 3.9 and 1.6 +/-
      4.5 mmHg when calibrated using brachial mean and diastolic and brachial systolic
      and diastolic pressures, respectively. CONCLUSION: Central systolic blood
      pressure can be obtained from a brachial cuff waveform with an accuracy
      comparable to that of a tonometer.

PMID- 22466801
TI  - Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with
      allopregnanolone.
AB  - Premutation CGG repeat expansions (55-200 CGG repeats; preCGG) within the fragile
      X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia
      syndrome (FXTAS). Defects in neuronal morphology and migration have been
      described in a preCGG mouse model. Mouse preCGG hippocampal neurons (170 CGG
      repeats) grown in vitro develop abnormal networks of clustered burst (CB) firing,
      as assessed by multielectrode array recordings and clustered patterns of
      spontaneous Ca(2+) oscillations, neither typical of wild-type (WT) neurons.
      PreCGG neurons have reduced expression of vesicular GABA and glutamate (Glu)
      transporters (VGAT and VGLUT1, respectively), and preCGG hippocampal astrocytes
      display a rightward shift on Glu uptake kinetics, compared with WT. These
      alterations in preCGG astrocytes and neurons are associated with 4- to 8-fold
      elevated Fmr1 mRNA and occur despite consistent expression of fragile X mental
      retardation protein levels at ~50% of WT levels. Abnormal patterns of activity
      observed in preCGG neurons are pharmacologically mimicked in WT neurons by
      addition of Glu or the mGluR1/5 agonist, dihydroxyphenylglycine, to the medium,
      or by inhibition of astrocytic Glu uptake with dl-threo-beta-benzyloxyaspartic
      acid, but not by the ionotropic Glu receptor agonists, alpha-2-amino-3-(5-methyl
      3-oxo-1,2-oxazol-4-yl) propanoic acid or N-methyl-d-aspartic acid. The mGluR1 (7
      (hydroxyimino)cyclopropa [b]chromen-1a-carboxylate ethyl ester) or mGluR5 (2
      methyl-6-(phenylethynyl)pyridine hydrochloride) antagonists reversed CB firing.
      Importantly, the acute addition of the neurosteroid allopregnanolone mitigated
      functional impairments observed in preCGG neurons in a reversible manner. These
      results demonstrate abnormal mGluR1/5 signaling in preCGG neurons, which is
      ameliorated by mGluR1/5 antagonists or augmentation of GABA(A) receptor
      signaling, and identify allopregnanolone as a candidate therapeutic lead.

PMID- 22466805
TI  - What is still missing in acute-phase treatment of stroke: a prospective
      observational study.
AB  - Early recognition of stroke symptoms and activation of emergency medical service
      (EMS) positively affects prognosis after a stroke. To assess stroke awareness
      among stroke patients and medical personnel in the catchment area of Verona
      Hospital and how it affects stroke care, we prospectively studied timing of acute
      stroke care in relation to patients' characteristics. Patients admitted to
      Medical Departments of Verona University Hospital between January 1st and
      December 31st 2009 with a diagnosis of TIA or stroke were enrolled. Outcome
      measures were: time between (i) symptoms onset and hospital arrival, (ii)
      hospital arrival and brain CT scan, blood examination, ECG and neurological
      evaluation. The following patient/event characteristics were also collected:
      means of hospital arrival, sex, age, degree of disability, type of event (first
      or recurrent) and acute-phase treatment. Of 578 patients providing complete
      information, 60 % arrived to the emergency department with the EMS (EMS+ group),
      while 40 % arrived on their own (EMS-). EMS+ group was older than EMS- (mean age
      76.2, SD 13.2, vs. 72.3, SD 13, respectively), displayed more severe symptoms
      (mRS 4 vs. 2) and shorter time interval between symptoms onset and hospital
      arrival, hospital arrival and CT scan, ECG, laboratory tests and neurological
      evaluation (p < 0.0001); 22 % of the EMS+ patients were stroke recurrences versus
      29 % of the EMS- (p = 0.058); 85 % of thrombolised patients were EMS+. We
      conclude that there is a lack of awareness of stroke symptoms and risks of
      recurrence even among patients who already had a stroke and among medical
      personnel.

PMID- 22466806
TI  - Biochemical characterization of recombinant methionine aminopeptidases (MAPs)
      from Mycobacterium tuberculosis H37Rv.
AB  - Methionine aminopeptidase (MAP) performs the essential post-translational N
      terminal methionine excision (NME) of nascent polypeptides during protein
      synthesis. To characterize MAP from Mycobacterium tuberculosis, two homolgues,
      mapA (Rv0734) and mapB (Rv2861c), were over expressed and purified as recombinant
      proteins in E. coli. In vitro activity assay of apo-MtbMAPs using L-Met-p-nitro
      anilide as substrate revealed MtbMAP A to be catalytically more efficient
      compared to MtbMAP B. Ni(2+) was the best activator of apo-MtbMAP A, whereas
      Ni(2+) and Co(2+) activated apo-MtbMAP B equally. MtbMAP B showed higher thermo
      stability, but was feedback inhibited by higher concentrations of L-methionine.
      Aminopeptidase inhibitors like actinonin and bestatin inhibited both MtbMAPs,
      more prominently MtbMAP B. Among the site-directed mutants of MtbMAP B,
      substitution of metal-binding residue D142 completely abolished enzyme activity,
      whereas substitution of residues forming S1' pocket, C105S and T94C, had only
      moderate effects on substrate hydrolysis. Present study identified a specific
      insertion region in MtbMAP A sequence which differentiates it from other
      bacterial and eukaryotic MAPs. A deletion mutant lacking amino acids from this
      insertion region (MtbMAP A-?164-176) was constructed to probe into their
      structural and functional role in activity and stability of MtbMAP A. The limited
      success in soluble expression of this deletion mutant suggests further
      optimizations of expression conditions or alternative bioinformatics approaches
      for further characterization of this deletion mutant of MtbMAP A.

PMID- 22466807
TI  - Activation of PPARdelta up-regulates the expression of insulin gene transcription
      factor MafA and ameliorates glucose-induced insulin secretion impaired by
      palmitate.
AB  - PPARdelta, a member of the peroxisome proliferator-activated receptor
      superfamily, plays a key role in the transcriptional regulation of genes involved
      in cellular lipid and energy metabolism. Therefore, PPARdelta may represent a new
      target for the treatment of obesity, hyperlipidemia, and type 2 diabetes. MafA is
      a beta-cell-specific and glucose-regulated transcriptional activator for insulin
      gene expression and plays a crucial role in pancreas development, beta-cell
      differentiation as well as maintenance of beta-cell function. However, little is
      known about how PPARdelta regulates MafA and ameliorates glucose-stimulated
      insulin secretion impaired by free fatty acids (FFA). In the present study, we
      evaluated the basal insulin secretion (BIS), glucose-stimulated insulin secretion
      (GSIS), and insulin secretion index (ISI) of INS-1E cells that were cultured in
      media supplemented with or without 0.5 mM palmitate and treated with or without a
      PPARdelta agonist (GW501516) or PPARdelta siRNA. The expression of MafA, glucose
      transportor-2 (GLUT2), and insulin was found to be up-regulated in cells treated
      with GW501516. Finally, analysis of the level of JNK phosphorylation revealed
      that activated PPARdelta could inhibit the activation of JNK and increase the
      expression of MafA. Accordingly, the insulin secretion dysfunction in lipotoxic
      INS-1E cells was improved. Collectively, these results demonstrate that
      activation of PPARdelta improves insulin secretion impaired by palmitate and
      plays a role in the JNK-MafA-GLUT2 pathway.

PMID- 22466809
TI  - Pressure effects on the magnetic behaviour of copper (II) compounds: magnetic
      ordering of layered organic/inorganic magnets.
AB  - The high hydrostatic pressure effect on the magnetic properties of the layered
      hybrid compounds Cu(2)(OH)(3)(C(n)H(2n+1)CO(2)).mH(2)O with distance between
      magnetic layers of up to 40 A is studied. It is shown that the temperature of the
      ferromagnetic ordering decreases linearly with pressure increase. From
      measurements of susceptibility in the paramagnetic region, using both quantum
      Heisenberg and Ising exchange coupling models in layers and dipole interaction
      between layers, the in- and interlayer interactions are deduced. The dipole
      interactions are calculated and are shown to coincide with the model of Ising
      interactions in the layers. The value and decrease of T(c) under pressure are
      mainly driven by the value and decrease of the in-plane interactions. The
      formation of the long range ordering in the layered sample with dipolar
      interaction between layers is analysed. As a conclusion it is suggested that for
      designing high temperature ferromagnetism in layer compounds it is enough to have
      large in-plane interactions of ions with specific symmetry in layers and weak
      dipole interactions between layers.

PMID- 22466808
TI  - Polyhydroxylated fullerene C60(OH)44 suppresses intracellular lipid accumulation
      together with repression of intracellular superoxide anion radicals and
      subsequent PPARgamma2 expression during spontaneous differentiation of OP9
      preadipocytes into adipocytes.
AB  - Reactive oxygen species has been suggested to be one of the key factors
      associated with the development of obesity. During spontaneous differentiation of
      mouse stromal preadipocytes OP9 into adipocytes, intracellular superoxide anion
      radicals (O (2) (-.) ) level markedly increases and is accompanied by a
      significant elevation of intracellular lipid accumulation. This differentiation
      dependent increase in intracellular O (2) (-.) level positively correlated with
      the intracellular augmentation of the lipid level. Super-highly hydroxylated
      fullerene (SHH-F; C(60)(OH)(44)), a novel polyhydroxylated fullerene derivative,
      quenched intracellular O (2) (-.) , and lipid accumulation to 38.7 and 42.7 % of
      that in the control, respectively. By thin-layer chromatographic analysis of
      extracted cellular lipid components, SHH-F clearly decreased the triglycerides
      ratio in the whole lipid droplet fraction, but scarcely influenced other lipids
      components. PPARgamma2 expression, which plays a key role in regulating
      adipogenic differentiation, was significantly suppressed by SHH-F at the late
      stage of differentiation, with unaltered PPARgamma1 expression. The intracellular
      superoxide anion radical augmentation preceded expression of PPARgamma2, strongly
      suggesting that the primary O (2) (-.) generation was closely associated with
      lipid accumulation and subsequent PPARgamma2 induction. These results indicate
      that SHH-F suppresses intracellular lipid accumulation, particularly in lipid
      droplets, and decreases O (2) (-.) level and subsequent PPARgamma2 upregulation
      during spontaneous differentiation of OP9 preadipocytes into adipocytes.

PMID- 22466810
TI  - Relationship between biomarkers and subsequent clinical and angiographic
      restenosis after paclitaxel-eluting stents for treatment of STEMI: a HORIZONS-AMI
      substudy.
AB  - Drug-eluting stents (DES) reduce the incidence of in-stent restenosis (ISR) after
      primary percutaneous coronary intervention (PCI) for ST-elevation myocardial
      infarction (STEMI). Whether the use of biomarkers might be of utility to identify
      patients who remain at risk for DES ISR after primary PCI has never been
      examined. A total of 26 biomarkers were measured at enrollment and 30 days and
      analyzed at a central core laboratory in 501 STEMI patients from the HORIZONS-AMI
      trial. All patients underwent primary PCI with the TAXUS paclitaxel-eluting stent
      (PES), were scheduled for routine angiographic follow-up at 13 months, and were
      followed for 3 years. Mean in-stent late-loss was 0.28 +/- 0.57 mm, and target
      lesion revascularization (TLR) at 3 years occurred in 9.1 % of patients. Low
      levels of interleukin-6 (IL-6) and placental growth factor (PLGF) at admission
      were associated with both higher in-stent late loss and ischemia-driven TLR.
      Additionally, low admission levels of cardiotrophin-1 (CT-1) were associated with
      higher rates of ischemia-driven TLR. At 30-day follow-up lower values of IL-1ra
      (IL-1ra), matrix metalloproteinase 9 (MMP9), and myeloperoxidase (MPO), and a
      decline relative to admission in IL-1ra, monocyte chemotactic protein-1 (MCP-1),
      and MMP9 were associated with higher in-stent late loss. Low values of IL-6 at 30
      days were also associated with ischemia-driven TLR. After multivariate
      adjustment, only MPO at 30 days and a decline of MCP-1 between admission and 30
      days were associated with in-stent late loss, and only CT-1 was associated with
      TLR. MPO at 30 days and a decline of MCP-1 between admission and 30 days were
      independently associated with in-stent late loss, and CT-1 was associated with
      TLR. Additional studies to confirm and validate the utility of these biomarkers
      are warranted.

PMID- 22466811
TI  - Platelet glycoprotein IIIA PIA2 polymorphism is associated with ST elevation
      acute myocardial infarction in young Mexican population.
AB  - Platelet membrane glycoprotein IIb/IIIa plays an important role in adhesion and
      platelet aggregation. Polymorphisms of genes in platelet activation and
      fibrinolysis have been associated with myocardial infarction (MI), however this
      has not been confirmed by others, and results are still controversial. The aim of
      this study was to determine the frequency distribution and association of
      polymorphism in the platelet glycoprotein GPIIIa PLA/A2 and the possible
      interaction with the 4G/5G in the plasminogen activator inhibitor genes with ST
      elevation acute myocardial infarction (STEAMI) in young Mexican subjects. A total
      of 254 unrelated patients with first STEAMI <=45 years of age, who were admitted
      to a cardiovascular intense care unit and 254 healthy controls matched by age and
      gender were recruited from January 2006 and May 2011. The PIA1/A2 and 4G/5G
      polymorphism were determined in all participants by a PCR restriction based
      restriction endonuclease digestion. There was a difference in the PIA2 allele
      distribution between both groups (P = 0.001). Also, we found an increased percent
      of 4G allele in the group of patients compared to control group (P = 0.001).
      There was an increased risk for STEAMI in carries with the allele PIA2 and 4G (OR
      = 4.3, CI 95 % 1.7-6.5). The modifiable risk factors such: smoking, hypertension,
      family history of cardiovascular disease, and dyslipidemia were associated with
      myocardial infarction. This is the first study to evaluate the role of gene
      polymorphism in both the thrombotic and fibrinolytic pathways in young Mexican
      individuals with STEAMI and suggest a synergistic effect between PIA2 and 4G
      allele.

PMID- 22466812
TI  - Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after
      non-ST-elevation myocardial infarction.
AB  - Prior studies demonstrated the association between the major adverse
      cardiovascular outcomes and both higher platelet and lower lymphocyte counts. Our
      study explores the value of the platelet/lymphocyte ratio (PLR) as a marker of
      long-term mortality in patients presented with non-ST segment elevation
      myocardial infarction (NSTEMI). This is an observational study with a total 619
      NSTEMI patients admitted to a tertiary center between 2004 and 2006. Patients
      were stratified into equal tertiles according to their admission PLR. The primary
      outcome, 4 year all-cause mortality, was compared among the PLR tertiles. The
      first, second and third PLR tertiles were PLR < 118.4, 118.4 <= PLR <= 176, and
      PLR > 176, respectively) included 206, 206 and 207 patients, respectively. There
      was a significant higher 4 year all-cause mortality in the higher PLR tertiles
      (the mortalities were 17, 23 and 42 % for the first, second and third PLR
      tertiles respectively, p < 0.0001). After exclusion of patients expired in the
      first 30 days, patients in the first PLR tertile had a significant lower 4 year
      mortality (33/205, 16 %) versus those in the third PLR tertile (72/192, 38 %), p
      < 0.0001. After controlling for Global Registry of Acute Coronary Events risk
      scores and other confounders, the hazard ratio of mortality increased 2 % per
      each 10 U increase of PLR (95 % CI 1.01-1.03, p < 0.0001). In patients with PLR
      >= 176, the mortality rate was statistically higher in those received mono
      antiplatelet (30/60 = 50 %) compared to those received dual antiplatelet therapy
      (48/149 = 32 %), p = 0.0018. However in PLR < 176, the mortality was not
      significantly different between mono-antiplatelet group (20/94 = 21 %) versus
      dual antiplatelets group (53/213 = 25 %), p = 0.56. The PLR is a significant
      independent predictor of long-term mortality after NSTEMI. Among patients with
      PLR > 176, patients with dual antiplatelet therapy had lower mortality versus
      those with mono-platelet therapy. Further studies are needed to clarify these
      findings.

PMID- 22466813
TI  - Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and
      factor VIII in patients undergoing hemodialysis.
AB  - Several studies have demonstrated that non-O blood groups subjects present an
      increased VTE risk as compared to those carrying O blood group. The aim of this
      study was to investigate the ABO blood groups influence on factor VIII (FVIII)
      activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients
      undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy
      subjects (control group) were eligible for this cross-sectional study. The ABO
      blood group phenotyping was performed by the reverse technique. FVIII activity
      was measured through coagulometric method, and VWF and ADAMTS13 antigens were
      assessed by ELISA. FVIII activity and VWF levels were significantly higher and
      ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P
      < 0.001, in three cases). HD patients carrying non-O blood groups showed a
      significant increase in FVIII activity (P = 0.001) and VWF levels (P < 0.001)
      when compared to carriers of O blood group. However, no significant difference
      was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in
      FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13
      levels (P = 0.005) were observed in subjects carrying non-O blood groups as
      compared to carriers of O blood group.Our data confirmed that ABO blood group is
      an important risk factor for increased procoagulant factors in plasma, as FVIII
      and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its
      metabolism, HD patients were not able to increase ADAMTS13 levels in order to
      compensate the increase of VWF levels mediated by ABO blood groups. Considering
      that non-O blood groups constitute a risk factor for thrombosis, it is reasonable
      to admit that A, B and AB HD patients need a careful and continuous follow-up in
      order to minimize thrombotic events.

PMID- 22466814
TI  - The incidence of venous thromboembolism following stroke and its risk factors in
      eastern China.
AB  - Few studies have documented the prevalence of venous thromboembolism (VTE) in the
      Chinese population. We aimed to investigate the incidence of VTE following stroke
      and to determine the potential risk factors for the onset of VTE in patients of
      eastern China. A prospective multi-center study was conducted. A total of 1,380
      patients with acute stroke received venous duplex ultrasound (VDU) examination on
      both lower limbs. The National Institutes of Health Stroke Scale (NIHSS), Barthel
      index (BI), Wells, and modified Rankin scale scores were determined. Among 1,380
      cases of acute stroke, 4.49 % (62 cases) had deep venous thrombosis (DVT) and
      0.80 % (11 cases) had pulmonary thromboembolism (PTE). In the cases of DVT, 48.4
      % had no clinical symptoms. The independent risk factors for the incidence of
      DVT, following the acute stage of stroke, were an age >= 70 years, bed-ridden, a
      Wells score >= 2, an NIHSS score of lower limbs >= 3, a low BI score, and an
      elevated concentration of D: -dimer. Rehabilitative and anti-coagulant therapy
      prevented the incidence of DVT following stroke. Moreover, an age >= 70 years,
      bed-ridden and having DVT were the independent risk factors for the incidence of
      PTE among stroke patients during the acute stage. Finally, 1.51 % of the patients
      had DVT whereas no PTE occurred during the period of the follow-up study. VDU
      examination is recommended for patients with acute stroke, which may help to
      diagnose and treat asymptomatic DVT early as well as prevent the subsequent
      incidence of PTE.

PMID- 22466815
TI  - Control of the alkali cation alignment in Prussian blue framework.
AB  - We found that the alignments of the alkali cations can be controlled by a
      distortion of Prussian blue framework; the rubidium ions form a rod structure in
      a distorted framework of Rb(0.85)Cu[Fe(CN)(6)](0.95).1.3H(2)O, while the cesium
      ions are isolated dot structures in a non-distorted framework of
      Cs(0.97)Cu[Fe(CN)(6)](0.99).1.1H(2)O. The Madelung energy calculations revealed
      that the novel rod structure is stabilized by the alternating rotations of the
      [Fe(CN)(6)] units within the three-dimensional coordination polymer framework.

PMID- 22466816
TI  - Therapeutic effects of novel resin bonding systems containing bioactive glasses
      on mineral-depleted areas within the bonded-dentine interface.
AB  - This study aimed in evaluating the effects of two experimental resin bonding
      systems containing conventional Bioglass 45S5 (BAG) or Zinc-polycarboxylated
      bioactive glass (BAG-Zn) micro-fillers on the resin-bonded dentine interface
      after storage in a simulated body fluid solution (SBFS). Three resin bonding
      systems were formulated: Resin-A: (BAG containing); Resin-B; (BAG-Zn containing);
      Resin-C (no filler). The ability of the experimental resins to evoke apatite
      formation was evaluated using confocal Raman spectroscopy. Acid-etched dentine
      specimens were bonded, and prepared for AFM/nano-indentation analysis in a fully
      hydrated status to evaluate the modulus of elasticity (Ei) and hardness (Hi)
      across the interface at different SBFS storage periods. Further resin-dentine
      specimens were tested for microtensile bond strength after 24 h or 3 months of
      SBFS storage. SEM examination was performed after de-bonding and confocal laser
      microscopy was used to evaluate the ultramorphology of the interfaces and
      micropermeability. The resin A and B showed a consistent presence of apatite (967
      cm(-1)), reduced micropermeability within the resin-dentine interface and a
      significant increase of the Ei and Hi along the bonded-dentine interface after
      prolonged SBFS storage. Bond strength values were affected by the resin system (P
      < 0.0001) and by storage time (P < 0.0001) both after 24 h and 3 months of SBFS
      storage. In conclusion, resin bonding systems containing bioactive fillers may a
      have therapeutic effect on the nano-mechanical properties and sealing ability of
      mineral-depleted resin-dentine interface.

PMID- 22466817
TI  - Controlled release of triamcinolone acetonide from polyurethane implantable
      devices: application for inhibition of inflammatory-angiogenesis.
AB  - The purpose of this study was to develop triamcinolone acetonide-loaded
      polyurethane implants (TA PU implants) for the local treatment of different
      pathologies including arthritis, ocular and neuroinflammatory disorders. The TA
      PU implants were characterized by FTIR, SAXS and WAXS. The in vitro and in vivo
      release of TA from the PU implants was evaluated. The efficacy of TA PU implants
      in suppressing inflammatory-angiogenesis in a murine sponge model was
      demonstrated. FTIR results revealed no chemical interactions between polymer and
      drug. SAXS results indicated that the incorporation of the drug did not disturb
      the polymer morphology. WAXS showed that the crystalline nature of the TA was
      preserved after incorporation into the PU. The TA released from the PU implants
      efficiently inhibited the inflammatory-angiogenesis induced by sponge discs in an
      experimental animal model. Finally, TA PU implants could be used as local drug
      delivery systems because of their controlled delivery of TA.

PMID- 22466818
TI  - A novel antibacterial resin composite for improved dental restoratives.
AB  - A novel furanone-containing antibacterial resin composite has been prepared and
      evaluated. compressive strength (CS) and Streptococcus mutans viability were used
      to evaluate the mechanical strength and antibacterial activity of the composites.
      The modified resin composites showed a significant antibacterial activity without
      substantially decreasing the mechanical strengths. With 5-30 % addition of the
      furanone derivative, the composite kept its original CS unchanged but showed a
      significant antibacterial activity with a 16-68 % reduction in the S. mutans
      viability. Further, the antibacterial function of the new composite was not
      affected by human saliva. The aging study indicates that the composite may have a
      long-lasting antibacterial function. Within the limitations of this study, it
      appears that the experimental antibacterial resin composite may potentially be
      developed into a clinically attractive dental restorative due to its high
      mechanical strength and antibacterial function.

PMID- 22466819
TI  - Cost-effectiveness analysis comparing epidural, patient-controlled intravenous
      morphine, and continuous wound infiltration for postoperative pain management
      after open abdominal surgery.
AB  - BACKGROUND: Continuous wound infiltration (CWI), i.v. patient-controlled
      analgesia (i.v.-PCA), and epidural analgesia (EDA) are analgesic techniques
      commonly used for pain relief after open abdominal surgery. The aim of this study
      was to evaluate the cost-effectiveness of these techniques. METHODS: A decision
      analytic model was developed, including values retrieved from clinical trials and
      from an observational prospective cohort of 85 patients. Efficacy criteria were
      based on pain at rest (VAS <= 30/100 mm at 24 h). Resource use and costs were
      evaluated from medical record measurements and published data. Probabilistic
      sensitivity analysis (PSA) was performed. RESULTS: When taking into account all
      resources consumed, the CWI arm (? 6460) is economically dominant when compared
      with i.v.-PCA (? 7273) and EDA (? 7500). The proportion of patients successfully
      controlled for their postoperative pain management are 77.4%, 53.9%, and 72.9%
      for CWI, i.v.-PCA, and EDA, respectively, demonstrating the CWI procedure to be
      both economically and clinically dominant. PSA reported that CWI remains cost
      saving in 70.4% of cases in comparison with EDA and in 59.2% of cases when
      compared with PCA. CONCLUSIONS: Device-related costs of using CWI for pain
      management after abdominal laparotomy are partly counterbalanced by a reduction
      in resource consumption. The cost-effectiveness analysis suggests that CWI is the
      dominant treatment strategy for managing postoperative pain (i.e. more effective
      and less costly) in comparison with i.v.-PCA. When compared with EDA, CWI is less
      costly with almost equivalent efficacy. This economic evaluation may be useful
      for clinicians to design algorithms for pain management after major abdominal
      surgery.

PMID- 22466820
TI  - Microvascular and macrovascular flow are uncoupled in early polymicrobial sepsis.
AB  - BACKGROUND: Microvascular dysfunction is considered to play an important
      pathophysiological role in sepsis. We addressed the hypothesis that macrovascular
      and microvascular flow are uncoupled in early sepsis, using a rodent model with
      well-characterized haemodynamic and biochemical markers of severity and
      subsequent mortality. METHODS: Male Wistar rats received either an
      intraperitoneal injection of faecal slurry (sepsis, n=14) or sterile saline
      (sham, n=6). Identical i.v. fluid resuscitation regimens were administered 2 h
      later through tethered lines while conscious. At 6 h post-sepsis and in sham
      operated controls, sidestream dark-field microvascular imaging of the left vastus
      lateralis muscle and transthoracic echocardiography were undertaken, again under
      anaesthesia. Non-operated rats (naive; n=5) served as negative controls. Mild and
      severe sepsis were defined a priori, based on the established predictive
      relationship between stroke volume and mortality in this model. RESULTS: Compared
      with sham-operated animals, there was a 19 (12-19)% and 62 (54-66)% decline in
      cardiac output in mild (n=8) and severe sepsis (n=6), respectively [median (inter
      quartile range), P<0.0001]. Blinded assessment of microvascular imaging revealed
      that the microvascular flow index (MFI) was impaired in sepsis and in sham
      operated controls (P<0.01), regardless of the degree of reduction in stroke
      volume and cardiac output. The MFI heterogeneity index revealed that only naive
      rats displayed a normal microvascular flow pattern. CONCLUSIONS: Microvascular
      flow is impaired during early sepsis and uncoupled from macrovascular function.
      The severity of macrovascular/cardiovascular compromise in early sepsis is not
      reflected by microvascular changes. Furthermore, surgery alone causes significant
      microvascular derangement, highlighting the importance of appropriate control
      subjects when using this technique.

PMID- 22466821
TI  - Reducing tidal volume and increasing positive end-expiratory pressure with
      constant plateau pressure during one-lung ventilation: effect on oxygenation.
AB  - BACKGROUND: It is no longer safe to use large tidal volumes (V(T)) (>8 ml kg(-1))
      for one-lung ventilation (OLV), and limiting plateau pressure should be a major
      objective. Due to the specificity of OLV, the use of positive end-expiratory
      pressure (PEEP) remains controversial. This study determined whether at the same
      low plateau pressure, reducing V(T) and increasing PEEP were not inferior to
      larger V(T) and lower PEEP ventilation in terms of oxygenation. METHODS: This
      prospective, randomized, non-inferiority, cross-over trial included 88 patients
      undergoing open thoracotomy who received two successive ventilatory strategies in
      random order: V(T) (8 ml kg(-1) of ideal body weight) with low PEEP (5 cm H(2)O),
      or low V(T) (5 ml kg(-1)) with a high PEEP. Respiratory rate and PEEP were,
      respectively, adjusted to maintain constant ventilation and plateau pressure. The
      primary endpoint was the ratio under each ventilatory strategy. RESULTS: The non
      inferiority of low-V(T) ventilation could not be established. The mean adjusted
      ratio was lower overall during low-V(T) ventilation, and differences between the
      two ventilatory modes varied significantly according to baseline (T0). Decreased
      oxygenation during low V(T) was smaller when baseline values were low. Systolic
      arterial pressure was not lower during low-V(T) ventilation. CONCLUSION: During
      OLV, lowering V(T) and increasing PEEP, with the same low plateau pressure,
      reduced oxygenation compared with larger V(T) and lower PEEP. This strategy may
      reduce the risk of lung injury, but needs to be investigated further.

PMID- 22466822
TI  - Deep echo attenuation without calcification increases the risk of periprocedural
      myonecrosis after elective percutaneous coronary intervention in patients with
      coronary artery disease.
AB  - OBJECTIVE: To investigate the clinical factors, including intravascular
      ultrasound (IVUS) findings, associated with percutaneous coronary intervention
      (PCI)-related periprocedural myonecrosis (PM) in patients with stable coronary
      artery disease (CAD). METHODS: The study included 46 patients (mean age 65+/-2 y,
      37 men) with stable CAD who underwent elective PCI using IVUS and a Doppler flow
      guidewire. In addition to routine IVUS measurements, the presence of deep echo
      attenuation (DEA) without calcification was assessed. The sum of all high
      intensity transient signals (HITS) after a balloon deflation procedure was
      calculated using a Doppler flow guidewire. PM was defined as an elevation in
      troponin T to >0.03 ng/mL 24-hour after PCI. Patients were divided into 2 groups
      on the basis of the presence or absence of PM. RESULTS: PM was identified in 17
      patients (37%). Estimated glomerular filtration ratio was lower in the PM group
      (p=0.021). Target vessel distribution was different between the groups (p=0.004).
      Positive remodeling and DEA, as observed on IVUS, were more common in the PM
      group (p=0.03 and p<0.0001, respectively). The total number of HITS was higher in
      the PM group (p=0.003). Logistic regression analysis demonstrated that the
      presence of DEA (p=0.003) was the sole factor associated with the occurrence of
      PM. CONCLUSION: These results demonstrated that DEA is an important factor
      associated with PM in patients who underwent an elective PCI. Therefore, IVUS to
      determine the presence of DEA should be performed before PCI.

PMID- 22466823
TI  - Associations of insulin resistance and glycemic control with the risk of kidney
      stones.
AB  - OBJECTIVE: The associations of insulin resistance and glycemic control with the
      risk of kidney stones were explored. METHODS: Generally healthy Japanese
      (n=2,171) who visited Saiseikai Central Hospital (Tokyo, Japan) for a health
      check were included in a cross-sectional study. We calculated odds ratios (OR) of
      having kidney stones in terms of four measures: fasting serum insulin,
      homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma
      glucose (FPG) and glycosylated hemoglobin (HbA1c), adjusting for possible risk
      factors for kidney stones. RESULTS: Fasting serum insulin and HOMA-IR were non
      significantly associated with the risk of kidney stones, whereas FPG and HbA1c
      were significantly associated. Compared with those with an FPG of <100 mg/dL, the
      ORs in those with an FPG of 100 to <126 mg/dL and >=126 mg/dL were 1.38 (95%
      confidence interval [CI] =0.95-2.00) and 1.83 (95% CI =1.09-3.06) (p for trend
      =0.016). In relation to those with an HbA1c of <5.5%, the ORs in those with an
      HbA1c of 5.5 to <6.0%, 6.0% to <6.5% and >=6.5% were 1.16 (95% CI =0.76-1.79),
      1.25 (95% CI =0.70-2.23) and 1.98 (95% CI =1.11-3.52), respectively (p for trend
      =0.027). The significant associations between glycemic control measures and the
      risk of kidney stones were preserved even after the adjustment for factors
      related to insulin resistance. CONCLUSION: Glycemic control could be an
      independent risk factor for kidney stones.

PMID- 22466824
TI  - Prognostic factors in malignant pleural mesothelioma: a retrospective study.
AB  - OBJECTIVE: The incidence of malignant pleural mesothelioma (MPM) in Japan is
      predicted to increase over the next few decades. Prognostic factors remain
      unclear although several studies have reported this disease. In this study, we
      examined the prognostic factors of MPM from single institution practice data and
      tested the scoring systems of past reports. METHODS: We retrospectively obtained
      clinical data from the medical records of patients who were diagnosed with MPM
      from 1991 to 2010. The European Organization for Research and Treatment of Cancer
      prognostic score (EPS) was calculated. RESULTS: We surveyed the records of 68
      patients. Univariate analysis showed that significant prognostic factors were
      histological type, stage, performance status (PS), chemotherapy, and lactate
      dehydrogenase (LD). Multivariate analysis identified stage, PS and LD as
      independent prognostic factors. Low-risk group (EPS <=1.27) survival was
      significantly better than that of the high-risk group (EPS >1.27) (17.0 months
      vs. 8.0 months; p=0.002). CONCLUSION: Stage, PS and LD were demonstrated to be
      independent prognostic factors. An EPS >1.27 was still considered a poor
      prognosis indicator in the practice data of MPM.

PMID- 22466825
TI  - Lung inflation training using a positive end-expiratory pressure valve in
      neuromuscular disorders.
AB  - OBJECTIVE: Respiratory muscle weakness causes alveolar hypoventilation and
      reduced lung compliance in neuromuscular disorders. Lung inflation is important
      to prevent secondary pulmonary complications however respiratory and laryngeal
      dysfunction often hamper lung inflation. There is a need for a convenient and low
      cost device that enables effective lung inflation. We tested a lung inflation
      training method using a positive end-expiratory pressure (PEEP) valve. METHODS:
      Vital capacity (VC), maximum insufflation capacity (MIC) and peak cough flow
      (PCF) as well as PEEP lung inflation capacity (PIC) were assessed in 93
      neuromuscular patients. Consecutive PIC training was done for 4 months in six
      tracheostomized Duchenne muscular dystrophy (DMD) patients and PIC was assessed
      before and after training. RESULTS: PIC training was practicable in all
      participants and no serious adverse events were detected. PIC was significantly
      higher than VC or MIC in all disorders, although MIC was higher than VC in DMD
      only. Patients with dysphagia showed lower MIC and PCF compared with non
      dysphagic patients. PIC was as low as 345+/-77 mL in tracheostomized DMD
      patients; however consecutive training increased it up to 619+/-205 mL.
      CONCLUSION: The PEEP valve enabled effective lung inflation regardless of
      laryngeal function. Consecutive training can improve lung condition even in
      advanced cases. Early introduction of PIC training could be effective at
      preventing respiratory complications in patients with neuromuscular disorders.

PMID- 22466826
TI  - Moderate accuracy of peripheral eosinophil count for predicting eosinophilic
      phenotype in steroid-naive non-atopic adult asthmatics.
AB  - BACKGROUND AND AIM: Eosinophilic phenotype, sputum eosinophil count >=3%, of
      asthma is a valuable clinical parameter. However, measurement of sputum
      inflammatory cells is time-consuming and requires specialized personnel. A
      simpler surrogate, such as peripheral eosinophil count, would be beneficial. The
      aim of this study was to assess the value of peripheral eosinophil count for
      predicting the eosinophilic phenotype of adult asthmatics. MATERIALS AND METHODS:
      This retrospective study was conducted in 192 adult asthmatics. Sputum and venous
      blood were collected at the same visit and analyzed for cell differential.
      Receiver-operating characteristic (ROC) curve analysis was used to assess the
      relationship between eosinophilic phenotype and peripheral eosinophil count.
      RESULTS: Peripheral eosinophil count, derived from the ROC curve, of more than
      210 cells/mm(3) yielded 67.7% sensitivity and 66.2% specificity [area under the
      curve (AUC)=0.698, p=0.0001] for identifying the eosinophilic phenotype in the
      total patients. Multiple regression analysis revealed that steroid treatment and
      atopy significantly influenced the peripheral eosinophil count. Within the
      steroid-naive subgroup, a peripheral eosinophil count of >190 cells/mm(3) yielded
      76.3% sensitivity and 67.4% specificity (AUC=0.730, p<0.0001) for identifying
      eosinophilic phenotype, while in the steroid treated subgroup, the AUC was 0.554
      (p=0.4985). Within the steroid-naive non-atopic subgroup, a peripheral eosinophil
      count of >190 cells/mm(3) yielded 73.1% sensitivity and 79.3% specificity
      (AUC=0.809, p=0.0001) for identifying the eosinophilic phenotype, while in the
      steroid-naive atopic subgroup, the AUC was 0.588 (p=0.2723). CONCLUSION:
      Peripheral eosinophil count is able to identify the presence of eosinophilic
      phenotype in steroid-naive non-atopic adult asthmatics with moderate accuracy.

PMID- 22466827
TI  - Sonazoid-enhanced ultrasonography and Ga-EOB-DTPA-enhanced MRI of hepatic
      inflammatory pseudotumor: a case report.
AB  - A liver neoplasm was found in a 63-year-old man with alcoholic liver disease.
      Sonazoid-enhanced ultrasonography (US) showed that the neoplasm was isoechoic at
      the early vascular phase and hypoechoic at the post-vascular phase. Gadolinium
      ethoxybenzyl-diethylenetriamine-enhanced magnetic resonance imaging (MRI) showed
      that the neoplasm was hypointense at the hepatobiliary phase. We suspected that
      it was a malignant tumor. By needle biopsy, however, the neoplasm was diagnosed
      as an inflammatory pseudotumor (IPT). We encountered a rare case of hepatic IPT,
      the differential diagnosis of which was difficult to distinguish from malignant
      tumor. Here, we report new US and MRI findings of hepatic IPT.

PMID- 22466828
TI  - Poorly differentiated neuroendocrine carcinoma of the pancreas responsive to
      combination therapy with gemcitabine and S-1.
AB  - Poorly differentiated neuroendocrine carcinoma is a very rare malignancy, but it
      is characterized by agressive histological features and a poor clinical
      prognosis. We report a 42-year-old man who had poorly differentiated
      neuroendocrine carcinoma of the pancreas with multiple liver metastases. We
      administrated combined chemotherapy with S-1 and gemcitabine. This treatment was
      efficacious and well tolerated, and then this patient obtained objective partial
      response for 7 months and survived for 13 months after the diagnosis. This case
      suggests that S-1 and gemcitabine combination produce beneficial responses for
      patients with this disease.

PMID- 22466829
TI  - Autoimmune pancreatitis with histologically proven lymphoplasmacytic sclerosing
      pancreatitis with granulocytic epithelial lesions.
AB  - Recent histological and clinical studies have suggested the existence of 2
      distinct types of autoimmune pancreatitis (AIP): type 1 AIP related to IgG4,
      exhibiting lymphoplasmacytic sclerosing pancreatitis (LPSP), and type 2 AIP
      related to granulocyte epithelial lesions (GELs), exhibiting idiopathic duct
      centric chronic pancreatitis (IDCP). We herein present a case of type 1 AIP with
      histologically proven LPSP with GELs. This patient had neither serum IgG4
      elevation nor MPD narrowing. In this case, the clinically and histologically
      atypical findings for type 1 AIP are intriguing.

PMID- 22466831
TI  - A case of isoniazid-induced thrombocytopenia: recovery with immunoglobulin
      therapy.
AB  - Treatment for a 51-year-old man with pulmonary tuberculosis was initiated with
      isoniazid, rifampicin, ethambutol, and pyrazinamide, and discontinued after 3
      weeks because of skin rash and itchiness. Isoniazid monotherapy was restarted
      after 2 weeks. Two days later, the platelet count decreased from 150 to
      4*10(3)/mm(3). Despite platelet transfusion and oral corticosteroid treatment,
      the platelet count did not recover. However, after a 2-day administration of
      intravenous immunoglobulin, the platelet count recovered to 209*10(3)/mm(3). This
      report describes a case of isoniazid-induced thrombocytopenia that was reversed
      with intravenous immunoglobulin, thus highlighting the efficacy of this treatment
      for this rare condition.

PMID- 22466830
TI  - A case of Takayasu arteritis with repeated coronary artery restenosis after drug
      eluting stent implantation successfully treated with a combination of steroids.
AB  - A 52-year-old woman with Takayasu arteritis developed acute coronary syndrome and
      received percutaneous coronary intervention (PCI). The patient experienced
      restenosis three times even with drug-eluting stent (DES) implantation. We
      started steroid administration after the fourth PCI to reduce inflammation due to
      autoimmunity. With DES and a steroid combination, the patient remained free of
      chest pain, and a follow-up angiography demonstrated good patency of the stent
      site. Since in-stent restenosis may result from a complicated combination of
      neointimal proliferation and autoimmune mechanisms, physicians should consider a
      combination of DES and a steroid for the treatment of coronary artery disease in
      Takayasu arteritis.

PMID- 22466832
TI  - Complete atrioventricular block and infective endocarditis in a patient with
      hypertrophic obstructive cardiomyopathy.
AB  - A 62-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) had
      complete atrioventricular (AV) block and subsequent cardiac standstill. A
      previous electrocardiogram revealed a bifascicular block pattern. Because he also
      suffered from infective endocarditis of the native aortic valve, surgical therapy
      (dual-chamber permanent pacing, myectomy of the left ventricular outflow tract,
      and valve replacement) was performed. Complete AV block unrelated to a procedure
      is a rare complication in patients with HOCM, but it may be life-threatening.
      Therefore, a pre-existing cardiac conduction disturbance should be specifically
      recognized as the aura of a higher degree of AV block.

PMID- 22466833
TI  - Proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) positive IgG4
      related retroperitoneal fibrosis: utility of PET-CT with 18F-fluorodeoxy glucose
      (FDG).
AB  - A 55-year-old man showed a serum creatinine level of 1.51 mg/dL, CRP of 0.79
      mg/dL, and proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) of 43.9
      EU (normal range: below 10). The serum levels and ratios of IgG1, IgG2, IgG3, and
      IgG4 to total IgG were 1,570 mg/dL (49%), 1,190 mg/dL (37%), 82 mg/dL (3%), and
      351 mg/dL (11%), respectively. Positron emission tomography and CT with (18)F
      fluorodeoxyglucose (PET-CT) demonstrated retroperitoneal fibrosis. After a
      diagnosis of IgG4-related retroperitoneal fibrosis with PR3-ANCA was made, oral
      prednisolone improved serum creatinine and the titer of PR3-ANCA to normal
      levels, with no abnormal findings on PET-CT.

PMID- 22466834
TI  - Rituximab treatment for adult patients with focal segmental glomerulosclerosis.
AB  - We present two cases with steroid-resistant nephrotic syndrome (SRNS) and two
      cases with steroid-dependent nephrotic syndrome (SDNS) due to focal segmental
      glomerulonephritis (FSGS) who were treated with a single dose of rituximab (375
      mg/m(2)). Although the two cases with SRNS showed no response, the two cases with
      SDNS achieved complete remission. The patients in whom the peripheral B-cell
      counts subsequently increased after the administration of rituximab demonstrated
      a relapse. Rituximab may be an effective treatment agent for SDNS with FSGS and
      the peripheral B-cell count may be a useful marker in such patients for
      preventing disease relapse.

PMID- 22466835
TI  - A case of sinobronchial syndrome complicated with myeloperoxidase antineutrophil
      cytoplasmic antibody associated vasculitis: review of the literature.
AB  - We report a case of long-standing sinobronchial syndrome complicated by
      microscopic polyangiitis (MPA) during the clinical course. The patient showed a
      mild elevation of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)
      17 months prior to the diagnosis of MPA. Subsequently, her MPO-ANCA level
      gradually became more elevated, and finally her MPO-ANCA level peaked when
      purpura appeared. Histologic examination of the skin biopsy was consistent with
      leukocytoclastic vasculitis. Based on the pathological and clinical findings, a
      diagnosis of MPA was made. Corticosteroid therapy finally led to a remission of
      MPA with normalized MPO-ANCA titers.

PMID- 22466836
TI  - Successful treatment of duodenal myeloid sarcoma with allogeneic bone marrow
      transplantation and additional radiotherapy.
AB  - Myeloid sarcoma (MS) is a tumor consisting of myeloid blasts that occurs at an
      anatomical site other than the bone marrow. We report the case of a 38-year-old
      man with duodenal MS who underwent an allogeneic bone marrow transplant in a non
      complete remission (CR) state. After the transplant, residual disease was
      suspected on a fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan,
      and additional radiotherapy resulted in CR, which has been maintained for 21
      months. FDG-PET/CT scanning is useful for evaluating residual myeloid sarcoma
      during the peritransplant period.

PMID- 22466837
TI  - Liver failure caused by light chain deposition disease associated with multiple
      myeloma.
AB  - Acute liver failure is an unusual complication in multiple myeloma. Here, we
      report a case of multiple myeloma with light chain deposition disease (LCDD) that
      presented with progressive jaundice due to intrahepatic cholestasis. Diagnosis
      was made after liver biopsy that showed deposition of kappa light chains
      occupying perisinusoidal spaces. The patient developed encephalopathy and liver
      failure and died despite prompt initiation of dexamethasone therapy. The current
      prognosis of multiple myeloma patients with liver failure due to LCDD is dismal.
      New therapeutic strategies might improve this condition.

PMID- 22466838
TI  - Recurrence of chronic active Epstein-Barr virus infection from donor cells after
      achieving complete response through allogeneic bone marrow transplantation.
AB  - We report the case of a 35-year-old woman with chronic active Epstein-Barr virus
      (EBV) infection (CAEBV). She underwent allogeneic bone marrow transplantation
      (BMT) from an unrelated male donor and achieved a complete response. However, her
      CAEBV relapsed one year after BMT. EBV-infected cells proliferated clonally and
      revealed a 46XY karyotype. In addition, the infecting EBV strain differed from
      that detected before BMT. These findings indicated that her disease had developed
      from donor cells. This is the first report of donor cell-derived CAEBV that
      recurred after transplantation, suggesting that host factors may be responsible
      for the development of this disease.

PMID- 22466839
TI  - A case of Japanese spotted fever complicated with central nervous system
      involvement and multiple organ failure.
AB  - Japanese spotted fever (JSF), first reported in 1984, is a rickettsial disease
      characterized by high fever, rash, and eschar formation. A 61-year-old man was
      admitted to a local hospital in Nagasaki City, Japan, after several days of high
      fever and generalized skin erythema. His condition deteriorated and laboratory
      findings indicated disseminated intravascular coagulation (DIC). The patient was
      transferred to our hospital with mental disturbance and status epilepticus.
      Treatment included minocycline, and new quinolone. Definitive diagnosis was made
      with a serological test showing increased antibody levels against Rickettsia
      japonica. Rickettsial infections are rare, but should be seriously considered for
      the differential diagnosis of aseptic meningitis and encephalitis, as they show
      no response to conventional antibiotic treatment.

PMID- 22466840
TI  - A case of reversible splenial lesions in late postpartum preeclampsia.
AB  - There have been reports of various etiologies associated with reversible splenial
      lesions manifested as obviously restricted diffusion. We describe for a 27-year
      old woman suffering from late postpartum preeclampsia associated with reversible
      splenial lesions. This association has not been reported to date. Awareness that
      profound late postpartum preeclampsia can rarely result in abnormalities of the
      splenium of the corpus callosum (SCC) may help clinicians avoid unnecessary
      diagnostic procedures and therapeutic interventions. Moreover, it must be stated
      that prediction of the clinical course based on DWI and ADC values should be used
      with caution.

PMID- 22466841
TI  - Coenzyme Q10 therapy in hereditary motor sensory neuropathy type VI with novel
      mitofusin 2 mutation.
AB  - Hereditary motor sensory neuropathy type VI (HMSN VI) is hereditary neuropathy
      accompanied by optic neuropathy. The feasibility of Coenzyme Q10 (CoQ10) as a
      treatment for subacute visual impairment of HMSN VI was examined. A 37-year-old
      patient with HMSN VI with a novel mitofusin 2 mutation was treated with high dose
      of CoQ10 (200 mg/day) for eight months. Visual impairment was partially resolved
      after CoQ10 therapy. High dose CoQ10 therapy may improve the prognosis of
      subacute visual impairment in HMSN VI. To confirm the effectiveness of CoQ10 on
      HMSN VI, further studies are needed.

PMID- 22466842
TI  - Progressive multiple cranial nerve palsies as the presenting symptom of meningeal
      carcinomatosis from occult colon adenocarcinoma.
AB  - We herein describe a rare case of meningeal carcinomatosis in a 77-year-old woman
      who had bilateral deafness as the initial symptom of a previously undetected
      colon cancer malignancy. Meningeal carcinomatosis should be considered in the
      differential diagnosis in cases of abrupt-onset sensorineural deafness. Both MRI
      scans and cerebrospinal fluid evaluation are necessary diagnostic tools, and
      should be used in conjunction as each of these procedures could have false
      negative results. This should apply even when there is no known primary
      malignancy.

PMID- 22466843
TI  - Characterization of dermatomyositis with coexistence of anti-Jo-1 and anti-SRP
      antibodies.
AB  - We describe a patient with dermatomyositis who presented with rapidly developing
      severe muscle weakness complicated by massive pleural effusion with interstitial
      lung disease. Myopathological analysis was suggestive of dermatomyositis. This
      patient showed both anti-Jo-1 and anti-SRP antibodies in serum. To our knowledge,
      the coexistence of these two myositis-specific autoantibodies (MSA) is considered
      extremely rare and is clearly an exception to the rule of having only one MSA.
      Our findings provide compelling evidence that the coexistence of these two MSAs
      may lead to more severe clinical symptoms, interacting in a complex fashion, thus
      expanding the clinical spectrum of idiopathic inflammatory myopathy.

PMID- 22466844
TI  - A case of posterior spinal artery syndrome in the cervical cord: a review of the
      clinicoradiological literature.
AB  - We describe a patient with posterior spinal artery (PSA) syndrome due to
      vertebral artery (VA) dissection. A 63-year-old woman developed neck pain,
      bilateral shoulder and arm numbness, and paraparesis after prolonged neck
      extension during a dental procedure. Neurological examination revealed sensory
      deficits in the legs, paraparesis, cerebellar ataxia, urinary retention and
      constipation. Magnetic resonance imaging disclosed T2-hyperintense lesions in the
      posterolateral C4-C7 cord with partial enhancement. T1-hyperintensity and
      stenosis were found in the right VA at C3-C5. These clinicoradiological findings
      suggested bilateral PSA syndrome and unilateral VA dissection. This is the fourth
      report of VA dissection-induced PSA syndrome.

PMID- 22466845
TI  - Recurrent brainstem lesions mimicking infarctions in an elderly patient with
      neuromyelitis optica spectrum disorder.
AB  - Anti-aquaporin-4 (AQP4) antibody is highly specific for neuromyelitis optica
      (NMO) and NMO spectrum disorder. Brainstem lesions sometimes show involvement in
      NMO and NMO spectrum disorder, and onset is usually diagnosed in young or middle
      aged adults. Here, we report the case of an 87-year-old woman with recurrent
      brainstem lesions and subsequent severe longitudinally extensive cervical cord
      lesions who was found to be positive for anti-AQP4 antibody. In patients with
      recurrent brainstem lesions, even in the elderly and those with symptoms
      mimicking infarction, NMO spectrum disorder should be considered as a
      differential diagnosis.

PMID- 22466846
TI  - "Possible primary antiphospholipid syndrome" with concurrent diffuse alveolar
      hemorrhaging and Libman-Sacks endocarditis mimicking catastrophic
      antiphospholipid syndrome.
AB  - Although antiphospholipid antibody syndrome (APS) is an autoimmune condition that
      is primarily characterized by arterial or venous thrombosis or pregnancy
      morbidity and the presence of antiphospholipid antibodies (aPL), recent reviews
      have introduced non-thromboembolic manifestations. We describe the case of a 58
      year-old woman with vegetation on the aortic valve, whose initial presentation of
      APS abruptly developed into diffuse pulmonary hemorrhage. Despite consecutive
      plasma exchange procedures and the administration of corticosteroids and high
      dose intravenous immunoglobulin, multiple brain infarctions developed, and the
      patient died of pneumonia. Although anecdotal, this case might serve as a useful
      example of the non-standard complications of fulminant APS.

PMID- 22466847
TI  - Pontine hyperperfusion during recovery from central pontine myelinolysis.

PMID- 22466848
TI  - Stroke presenting with monoparesis in the lower limb.

PMID- 22466849
TI  - Chemistry and biological activities of terpenoids from copaiba (Copaifera spp.)
      oleoresins.
AB  - Copaiba oleoresins are exuded from the trunks of trees of the Copaifera species
      (Leguminosae-Caesalpinoideae). This oleoresin is a solution of diterpenoids,
      especially, mono- and di-acids, solubilized by sesquiterpene hydrocarbons. The
      sesquiterpenes and diterpenes (labdane, clerodane and kaurane skeletons) are
      different for each Copaifera species and have been linked to several reported
      biological activities, ranging from anti-tumoral to embriotoxic effects. This
      review presents all the substances already described in this oleoresin, together
      with structures and activities of its main terpenoids.

PMID- 22466850
TI  - Essential oil from Cryptomeria japonica induces apoptosis in human oral
      epidermoid carcinoma cells via mitochondrial stress and activation of caspases.
AB  - Cryptomeria japonica D. Don (C. japonica) has been used in traditional medicines
      from Asia for a variety of indications, including liver ailments, and an
      antitussive, and for its antiulcer activities. We examined the cell viability and
      apoptosis of KB cells treated with C. japonica essential oil at several
      concentrations for 12 h by MTT assay, Hoechst-33258 dye staining, DNA
      fragmentation, flow cytometry (cell cycle), and Western blotting for mitochondria
      stress, activation of caspases, and poly (ADP-ribose) polymerase. The essential
      oil induced the apoptosis of KB cells in a dose-dependent manner, which was
      verified by DNA fragmentation, appearance of apoptotic bodies, and the sub-G1
      ratio. The essential oil also induced rapid and transient caspase-3 activity and
      cleavage of PARP of the KB cells. Treating the cells with the oil also caused
      changes in the mitochondrial level of the Bcl-2 family proteins such as Bcl-2 and
      Bax, thereby inducing the release of cytochrome c into the cytosol. The essential
      oil of C. japonica may have potential as a cancer chemopreventive and therapeutic
      agent.

PMID- 22466851
TI  - Inhibition of melanogenesis versus antioxidant properties of essential oil
      extracted from leaves of Vitex negundo Linn and chemical composition analysis by
      GC-MS.
AB  - This study was aimed at investigating the antimelanogenic and antioxidative
      properties of the essential oil extracted from leaves of V. negundo Linn and the
      analysis of the chemical composition of this essential oil. The efficacy of the
      essential oil was evaluated spectrophotometrically, whereas the volatile chemical
      compounds in the essential oil were analyzed by gas chromatography-mass
      spectrometry (GC-MS). The results revealed that the essential oil effectively
      suppresses murine B16F10 tyrosinase activity and decreases the amount of melanin
      in a dose-dependent manner. Additionally, the essential oil significantly
      scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals, and showed potent reducing
      power versus metal-ion chelating properties in a dose-dependent pattern. The
      chemical constituents in the essential oil are sesquiterpenes (44.41%),
      monoterpenes (19.25%), esters (14.77%), alcohols (8.53%), aromatic compound
      (5.90%), ketone (4.96%), ethers (0.4%) that together account for 98.22% of its
      chemical composition. It is predicted that the aromatic compound in the essential
      oil may contribute to its antioxidant activities. The results indicated that
      essential oil extracted from V. negundo Linn leaves decreased melanin production
      in B16F10 melanoma cells and showed potent antioxidant activities. The essential
      oil can thereby serve as an inhibitor of melanin synthesis and could also act as
      a natural antioxidant.

PMID- 22466852
TI  - Antioxidant, antimicrobial properties and phenolics of different solvent extracts
      from bark, leaves and seeds of Pongamia pinnata (L.) Pierre.
AB  - This study appraises the antioxidant and antimicrobial attributes of various
      solvent extracts (absolute methanol, aqueous methanol, absolute ethanol, aqueous
      ethanol, absolute acetone, aqueous acetone, and deionized water) from bark,
      leaves and seeds of Pongamia pinnata (L.) Pierre. Maximum extraction yield of
      antioxidant components from bark (16.31%), leaves (11.42%) and seeds (21.51%) of
      P. pinnata was obtained using aqueous methanol (20:80). Of the extracts tested,
      the bark extract, obtained with aqueous methanol, exhibited greater levels of
      total phenolics [6.94 g GAE/100 g dry weight (DW)], total flavonoids (3.44 g
      CE/100 g DW), inhibition of linoleic acid peroxidation (69.23%) and DPPH radical
      scavenging activity (IC(50) value, 3.21 MUg/mL), followed by leaves and seeds
      extracts. Bark extract tested against a set of bacterial and fungal strains also
      revealed the strongest antimicrobial activity with the largest inhibition zone
      and lowest minimum inhibitory concentration (MIC). HPLC analysis of aqueous
      methanol extracts from bark, leaves and seeds indicated the presence of
      protocatechuic, ellagic, ferulic, gallic, gentisic, 4-hydroxybenzoic and 4
      hydroxycinnamic acids in bark (1.50-6.70 mg/100 g DW); sorbic, ferulic, gallic,
      salicylic and p-coumaric acids in leaves (1.18-4.71 mg/100 g DW); vanillic,
      gallic and tannic acids in seeds (0.52-0.65 mg/100 g DW) as the main phenolic
      acids. The present investigation concludes that the tested parts of P. pinnata,
      in particular the bark, have strong potential for the isolation of antioxidant
      and antimicrobial agents for functional food and pharmaceutical uses.

PMID- 22466853
TI  - Synthesis and biological evaluation of novel benzothiazole-2-thiol derivatives as
      potential anticancer agents.
AB  - A series of novel benzothiazole-2-thiol derivatives were synthesized and their
      structures determined by 1H-NMR, 13C-NMR and HRMS (ESI). The effects of all
      compounds on a panel of different types of human cancer cell lines were
      investigated. Among them, pyridinyl-2-amine linked benzothiazole-2-thiol
      compounds 7d, 7e, 7f and 7i exhibited potent and broad-spectrum inhibitory
      activities. Compound 7e displayed the most potent anticancer activity on SKRB-3
      (IC(50) = 1.2 nM), SW620 (IC(50) = 4.3 nM), A549 (IC(50) = 44 nM) and HepG2
      (IC(50) = 48 nM) and was found to induce apoptosis in HepG2 cancer cells.

PMID- 22466854
TI  - Enzymatic activity enhancement of non-covalent modified superoxide dismutase and
      molecular docking analysis.
AB  - The enzyme activity of superoxide dismutase was improved in the pyrogallol
      autoxidation system by about 27%, after interaction between hydroxypropyl-beta
      cyclo-dextrin and superoxide dismutase. Fluorescence spectrometry was used to
      study the interaction between hydroxypropyl-beta-cyclodextrin and superoxide
      dismutase at different temperatures. By doing this, it can be found that these
      interactions increase fluorescence sensitivity. In the meantime, the synchronous
      fluorescence intensity revealed the interaction sites to be close to the
      tryptophan (Trp) and tyrosine (Tyr) residues of superoxide dismutase.
      Furthermore, molecular docking was applied to explore the binding mode between
      the ligands and the receptor. This suggested that HP-beta-CD interacted with the
      B ring, G ring and the O ring and revealed that the lysine (Lys) residues enter
      the nanocavity. It was concluded that the HP-beta-CD caused specific
      conformational changes in SOD by non-covalent modification.

PMID- 22466855
TI  - 4-N,N-Dimethylaminopyridine promoted selective oxidation of methyl aromatics with
      molecular oxygen.
AB  - 4-N,N-Dimethylaminopyridine (DMAP) as catalyst in combination with benzyl bromide
      was developed for the selective oxidation of methyl aromatics. DMAP exhibited
      higher catalytic activity than other pyridine analogues, such as 4
      carboxypyridine, 4-cyanopyridine and pyridine. The sp3 hybrid carbon-hydrogen (C
      H) bonds of different methyl aromatics were successfully oxygenated with
      molecular oxygen. The real catalyst is due to the formation of a pyridine onium
      salt from the bromide and DMAP. The onium salt was well characterized by NMR and
      the reaction mechanism was discussed.

PMID- 22466856
TI  - A nanomechanical mass sensor with yoctogram resolution.
AB  - Nanomechanical resonators have been used to weigh cells, biomolecules and gas
      molecules, and to study basic phenomena in surface science, such as phase
      transitions and diffusion. These experiments all rely on the ability of
      nanomechanical mass sensors to resolve small masses. Here, we report mass sensing
      experiments with a resolution of 1.7 yg (1 yg = 10(-24) g), which corresponds to
      the mass of one proton. The resonator is a carbon nanotube of length ~150 nm that
      vibrates at a frequency of almost 2 GHz. This unprecedented level of sensitivity
      allows us to detect adsorption events of naphthalene molecules (C(10)H(8)), and
      to measure the binding energy of a xenon atom on the nanotube surface. These
      ultrasensitive nanotube resonators could have applications in mass spectrometry,
      magnetometry and surface science.

PMID- 22466857
TI  - The emergence of multifrequency force microscopy.
AB  - In atomic force microscopy a cantilever with a sharp tip attached to it is
      scanned over the surface of a sample, and information about the surface is
      extracted by measuring how the deflection of the cantilever - which is caused by
      interactions between the tip and the surface - varies with position. In the most
      common form of atomic force microscopy, dynamic force microscopy, the cantilever
      is made to vibrate at a specific frequency, and the deflection of the tip is
      measured at this frequency. But the motion of the cantilever is highly nonlinear,
      and in conventional dynamic force microscopy, information about the sample that
      is encoded in the deflection at frequencies other than the excitation frequency
      is irreversibly lost. Multifrequency force microscopy involves the excitation
      and/or detection of the deflection at two or more frequencies, and it has the
      potential to overcome limitations in the spatial resolution and acquisition times
      of conventional force microscopes. Here we review the development of five
      different modes of multifrequency force microscopy and examine its application in
      studies of proteins, the imaging of vibrating nanostructures, measurements of ion
      diffusion and subsurface imaging in cells.

PMID- 22466858
TI  - Capsaicinoids lower plasma cholesterol and improve endothelial function in
      hamsters.
AB  - PURPOSE: Capsaicinoids are the active compounds in chili pepper. The present
      study investigated the effect of capsaicinoids on plasma lipids, functionality of
      aorta including atherosclerotic plaque development, cholesterol absorption
      biomarker, fecal sterol excretion, and gene expression of major receptors,
      enzymes, and transporters involved in cholesterol metabolism. METHODS: Hamsters
      were divided into five groups and fed a high-cholesterol diet containing 0 %
      (CON), 0.010 % (LD), 0.015 % (MD), 0.020 % (HD), and 0.030 % (VD) capsaicinoids,
      respectively, for 6 weeks. Plasma lipids were measured using the enzymatic kits,
      and the gene expression of transporters, enzymes, and receptors involved in
      cholesterol absorption and metabolism was quantified using the quantitative PCR.
      Endothelial function was assessed by measuring the acetylcholine-induced
      endothelium-dependent relaxations in aorta. RESULTS: Capsaicinoids reduced plasma
      total cholesterol, non-high-density lipoprotein cholesterol, and triacylglycerols
      with high-density lipoprotein cholesterol being unaffected. All four experimental
      groups had a decrease in the atherosclerotic plaque compared with CON. Dietary
      capsaicinoids increased the fecal excretion of total acidic sterols possibly
      mediated by up-regulation of cholesterol 7alpha-hydroxylase and down-regulation
      of liver X receptor alpha. Plasma sterol analysis demonstrated that capsaicinoids
      decreased the ratio of plasma campesterol/cholesterol, suggesting they decreased
      cholesterol absorption. Capsaicinoids could improve the endothelium-dependent
      relaxations and reduce the endothelium-dependent contractions by inhibiting the
      gene expression of COX-2. However, no dose-dependent effect of capsaicinoids on
      these parameters was seen. CONCLUSION: Capsaicinoids were beneficial in improving
      lipoprotein profile and aortic function in hamsters fed a high-cholesterol diet.

PMID- 22466860
TI  - The effect of alternative mating tactics on the fertilization success of a
      hermaphroditic seabass.
AB  - In the simultaneously hermaphroditic marine fish, Serranus subligarius, male role
      individuals are known to pair spawn, group spawn and streak spawn. While the
      effects of these common mating tactics on mating success in the male role have
      been well studied, their consequences for the reproductive success of the
      individuals taking the female role have received little attention. To investigate
      those consequences, I observed mating behaviors and quantified fertilization
      success in natural and experimental settings during the summers of 2005-2008 at
      three sites with different local population densities. I observed focal
      individuals in 15-min increments and recorded the total number of spawns, number
      of streak spawns, size of participating spawners, and fertilization rate. The
      occurrence of small-sized individuals in the local population is associated with
      higher frequencies of streaking behavior; these small fish are most often first
      year individuals reaching sexual maturity late in the spawning season
      (August/September). Spawns that included one or more streak spawners had a
      significantly lower average fertilization rate (89 %) than pair spawns without a
      streak spawner (97 %). This pattern was confirmed with a field manipulation
      experiment in which spawning events that included streakers again showed lower
      fertilization rates (93 %) than spawning events that did not include streakers
      (98 %). These lower fertilization rates occurred despite the fact that spawns
      that included multiple males produced, on average, 20 % more sperm than produced
      in spawns with only a single male. These results indicate that females incur a
      significant fitness cost when streakers invade a spawning event, a cost not
      attributable to sperm limitation or any direct effects on the female.

PMID- 22466861
TI  - Global meta-analysis for controlling factors on carbon stable isotope ratios of
      lotic periphyton.
AB  - Carbon stable isotope ratios (delta(13)C) are widely used to trace resource
      transfer pathways, yet delta(13)C variation in freshwater autotrophs is not yet
      fully understood. We have analyzed data from 42 published studies, supplemented
      with some unpublished data, to show the determinants of lotic periphyton
      delta(13)C. At large spatial scales, we observed broad differences in periphyton
      delta(13)C among biomes and consistent longitudinal variation related to
      watershed area. Longitudinal increases in delta(13)C indicate the importance of
      in-stream processes on lotic carbon cycles and autotroph delta(13)C variation. At
      local spatial scales, periphyton delta(13)C was negatively related to canopy
      cover and water current velocity and positively related to chlorophyll a density.
      Autotroph delta(13)C varied among taxonomic groups. Cyanobacteria and red algae
      had significantly higher and lower delta(13)C than other taxa, respectively. A
      hierarchical model across spatial scales showed that local controls for
      periphyton delta(13)C were nested by regional controls, which suggested that
      productivity and CO(2) availability determine delta(13)C. Overall, our results
      reveal general patterns of periphyton delta(13)C and provide improved information
      for study design and the use of delta(13)C in isotopic mixing models in lotic
      food web studies.

PMID- 22466862
TI  - Genetic effects of tank-forming bromeliads on the associated invertebrate
      community in a tropical forest ecosystem.
AB  - Within the area of community genetics there is an expanding volume of literature
      demonstrating how within-species genetic variation in temperate trees can have
      important effects on structuring animal and plant communities. The influence of
      intraspecific genetic variation on associated communities in relatively more
      complex ecosystems is only starting to be appreciated. Within tropical forests,
      epiphytic bromeliad plants often grow high in the canopy and create unique
      nutrient-rich microhabitats on which many invertebrate and vertebrate species
      depend. We investigated the influence of within-species genetic variation in the
      bromeliad Aechmea bracteata on the invertebrate microhabitat community. We found
      that more genetically similar bromeliad plants were host to more similar
      communities of juvenile-stage invertebrates, but not adult invertebrates. We
      discuss possible mechanisms for this, including differential survival and active
      female oviposition choice. Our work shows that the impact of within-species
      genetic variation on associated ecological communities may be more general than
      previously considered. These results agree with recent research suggesting that
      within-species genetic variation may perform a supporting ecosystem service for
      maintaining community and ecological processes.

PMID- 22466863
TI  - AZFa protein DDX3Y is differentially expressed in human male germ cells during
      development and in testicular tumours: new evidence for phenotypic plasticity of
      germ cells.
AB  - BACKGROUND: DDX3Y (DBY), located within AZoospermia Factor a (AZFa) region of the
      human Y chromosome (Yq11), encodes a conserved DEAD-box RNA helicase expressed
      only in germ cells and with a putative function at G1-S phase of the cell cycle.
      Deletion of AZFa results most often in germ cell aplasia, i.e. Sertoli-cell-only
      syndrome. To investigate the function of DDX3Y during human spermatogenesis, we
      examined its expression during development and maturation of the testis and in
      several types of testicular germ cell tumours (TGCTs), including the pre-invasive
      carcinoma in situ (CIS) precursor cells which are believed to originate from
      fetal gonocytes. METHODS: DDX3Y protein expression was analysed during
      development in different tissues by western blotting. The localization of DDX3Y
      in normal fetal and prepubertal testis tissue of different ages as well as in a
      series of distinct TGCT tissue samples (CIS, classical seminoma, spermatocytic
      seminoma, teratoma and embryonal carcinoma) was performed by
      immunohistochemistry. RESULTS: Germ cell-specific expression of DDX3Y protein was
      revealed in fetal prospermatogonia but not in gonocytes and not before the 17th
      gestational week. After birth, DDX3Y was expressed at first only in the nuclei of
      Ap spermatogonia, then also in the cytoplasm similarly to that seen after
      puberty. In CIS cells, DDX3Y was highly expressed and located predominantly in
      the nuclei. In invasive TGCT, significant DDX3Y expression was found in seminomas
      of the classical and spermatocytic type, but not in somatically differentiated
      non-seminomas, consistent with its germ-cell specific function. CONCLUSIONS: The
      fetal germ cell DDX3Y expression suggests a role in early spermatogonial
      proliferation and implies that, in men with AZFa deletion, germ cell depletion
      may begin prenatally. The strong expression of DDX3Y in CIS cells, but not in
      gonocytes, indicates phenotypic plasticity of CIS cells and suggests partial
      maturation to spermatogonia, likely due to their postpubertal microenvironment.

PMID- 22466865
TI  - Changing patient care orders from paper to computerized provider order entry
      based process.
AB  - The purpose of this study was to describe the extent of change in patient care
      orders primarily for six diagnoses, procedures, or conditions in a not-for-profit
      Midwestern rural referral hospital. A descriptive method was used to analyze
      changes in the order sets over time for chest pain with acute myocardial
      infarction, degenerative osteoarthritis with hip joint replacement and
      degenerative osteoarthritis with knee joint replacement procedures, coronary
      artery bypass graft procedures, congestive heart failure, and pneumonia. Ten
      items about service-specific order sets were abstracted during pre- and post-EHR
      implementation and a year later. We then examined use 5 years later. The findings
      illustrate how the order sets evolved with multiple nested order sets to
      facilitate computerized provider order entry with a rate greater than 70% by
      physicians. The total number of available patient care orders within the order
      sets increased primarily because of linked nested order sets related to
      medications and diagnostic tests. Five years later, 50% of the orders were
      medication orders. In conclusion, this was important to deploy the order sets
      within smaller critical-access hospital facilities to train providers in adopting
      order sets internally.

PMID- 22466864
TI  - Frequent aberrant expression of the human ether a go-go (hEAG1) potassium channel
      in head and neck cancer: pathobiological mechanisms and clinical implications.
AB  - Compelling evidence indicates that the human ether-a-go-go voltage-gated
      potassium channels (hEAG1) may represent new valuable membrane therapeutic
      targets and diagnostic/prognostic biomarkers in various cancers. This study is
      the first to investigate the expression of hEAG1 potassium channel subunit in
      both primary tumors and HNSCC-derived cell lines to ascertain its clinical and
      biological role in tumor progression. Our findings demonstrate that hEAG1 is
      frequently aberrantly expressed in a high percentage of primary tumors (83 %,
      45/54 cases) and HNSCC-derived cell lines (83 %, 10/12 cell lines). hEAG1
      expression increased during HNSCC progression and was more frequent in advanced
      tumors. Strikingly, hEAG1 expression was also detected in a notable proportion
      (39 %, 17/44 cases) of patient-matched normal adjacent mucosa, whereas no
      expression was detected in normal epithelia from non-oncologic patients without
      exposure to tobacco carcinogens. In an attempt to identify the underlying
      mechanisms of aberrant hEAG1 expression in HNSCC, we found that hEAG1 gene copy
      gain occurred at a low frequency (15 %, 13/88 cases) in primary tumors but was
      not observed in early stages of HNSCC tumorigenesis. Furthermore, this study
      provides original evidence supporting the involvement of histone acetylation
      (i.e., H3Ac and H4K16Ac activating marks) in the regulation of hEAG1 expression
      in HNSCC. In addition, functional studies in HNSCC cells further revealed that
      hEAG1 expression is a biologically relevant feature that promotes cell
      proliferation and invasion, although independently of its ion-conducting
      function. Our findings strongly support the notion that hEAG1 may represent a
      promising candidate as tumor marker and membrane therapeutic target for HNSCC
      treatment.

PMID- 22466866
TI  - Using podcasts to help students apply health informatics concepts: benefits and
      unintended consequences.
AB  - Despite requirements for robust health informatics education, a multitude of
      educators and policy analysts report that programs are not adequately preparing
      nurses to handle the bevy of technologies that will be a part of their practice.
      A series of 14 "Podcasted" exemplars were developed to help graduate online
      students visualize the application of health informatics concepts in real-world
      settings and to determine the impact of podcasting on student cognition,
      engagement, and satisfaction. Although no significant differences in student
      cognition scores or student engagement were found between course conditions,
      course satisfaction was significantly higher in Podcasted weeks of the course.
      Also, student engagement was positively correlated with aspects of course
      satisfaction and overall cognition scores under both course conditions. This
      result suggests that student engagement plays an important mediating role in
      improving cognition. Students' use of podcasting did produce a temporary drop in
      scores for one group; therefore, more research is needed to understand these
      unintended consequences. With distance/online education becoming mainstream, it
      is imperative that faculty deploy and confirm ways to improve student cognition,
      engagement, and satisfaction.

PMID- 22466867
TI  - Access to assisted reproductive technologies in France: the emergence of the
      patients' voice.
AB  - Is there any ethical justification for limiting the reproductive autonomy and not
      make assisted reproductive technologies available to certain prospective parents?
      We present and discuss the results of an interdisciplinary clinical ethics study
      concerning access to assisted reproductive technologies (ART) in situations which
      are considered as ethically problematic in France (overage or sick parents,
      surrogate motherhood). The study focused on the arguments that people in these
      situations put forward when requesting access to ART. It shows that requester's
      arguments are based on sound ethical values, and that their legitimacy is at
      least as strong as that of those used by doctors to question access to ART.
      Results reveal that the three implicit normative arguments that founded the law
      in 1994, which are still in force after the bioethics law revision in July 2011
      the welfare of the child, the illegitimacy of a "right to a child," and the
      defense of the so called "social order"-are challenged on several grounds by
      requesters as reasons for limiting their reproductive autonomy. Although these
      results are limited to exceptional situations, they are of special interest
      insofar as they give voice to the requesters' own ethical concerns in the ongoing
      political debate over access to ART.

PMID- 22466868
TI  - On the biophysics of cathodal galvanotaxis in rat prostate cancer cells: Poisson
      Nernst-Planck equation approach.
AB  - Rat prostate cancer cells have been previously investigated using two cell lines:
      a highly metastatic one (Mat-Ly-Lu) and a nonmetastatic one (AT-2). It turns out
      that the highly metastatic Mat-Ly-Lu cells exhibit a phenomenon of cathodal
      galvanotaxis in an electric field which can be blocked by interrupting the
      voltage-gated sodium channel (VGSC) activity. The VGSC activity is postulated to
      be characteristic for metastatic cells and seems to be a reasonable driving force
      for motile behavior. However, the classical theory of cellular motion depends on
      calcium ions rather than sodium ions. The current research provides a theoretical
      connection between cellular sodium inflow and cathodal galvanotaxis of Mat-Ly-Lu
      cells. Electrical repulsion of intracellular calcium ions by entering sodium ions
      is proposed after depolarization starting from the cathodal side. The disturbance
      in the calcium distribution may then drive actin polymerization and myosin
      contraction. The presented modeling is done within a continuous one-dimensional
      Poisson-Nernst-Planck equation framework.

PMID- 22466869
TI  - Driving forces and polymer hydrodynamics in the Soret effect.
AB  - A temperature gradient induces different driving forces on the components of a
      mixture which translates into their segregation. We show that these driving
      forces constitute the physical picture behind the thermodiffusion effect, and
      provide an alternative expression of the Soret coefficient which can be applied
      to both colloidal suspensions and molecular mixtures. To verify the validity of
      the formalism, we quantify the related forces in an Eulerian reference frame by
      non-equilibrium molecular simulations. Furthermore, we present an analytical
      argument to show that the hydrodynamic interactions need to be accounted for to
      obtain the proper scaling of the thermophoretic force. This result combined with
      the presented expression satisfactorily explains the experimentally known size
      dependence of the thermodiffusion coefficient in dilute polymer solutions.

PMID- 22466870
TI  - Comments on complete post-mortem decapitation in suicidal hanging.

PMID- 22466871
TI  - Symmetry: the key to diagnosing propeller strike injuries in sea mammals.

PMID- 22466872
TI  - Stroke-Unit and emergency medical service: a 48-month experience in northern
      Italy.
AB  - Since the therapeutic window for acute ischaemic stroke is very short, early
      arrival at emergency care rooms is mandatory. Emergency medical service (EMS),
      assuring fast patients transportations, plays a fundamental role in the
      management of stroke. We have prospectively analysed the utilisation of EMS in
      the management of stroke patients in a countryside area of northern Italy. Among
      patients presenting with an acute stroke during the period January 2007-December
      2010, those with an ascertained time of onset and documented ongoing brain
      ischaemia at neuroimaging were included in the study. For all of those patients,
      the personal data, means of arrival, nature of stroke, whether first stroke or
      recurrence, severity of stroke and the in-hospital outcome were recorded. Of
      1,188 patients hospitalised with a definite diagnosis of stroke, 757 patients
      were included in the study. Of those, 285 patients (37.6 %) were transported by
      EMS. EMS allowed earlier admissions (75 % within 3 h of stroke onset), but also
      transportation of patients of an older age (75 vs. 71 years, p < 0.001), and with
      more severe strokes (62 % of total anterior circulation infarctions). Our study
      confirms that EMS is essential in delivering the earliest therapy to patients
      with acute cerebral infarction living in an extra-urban area of northern Italy.
      However, work is needed in optimising EMS, since transported patients are often
      not prone to therapy.

PMID- 22466873
TI  - Intra-carotid cold magnesium sulfate infusion induces selective cerebral
      hypothermia and neuroprotection in rats with transient middle cerebral artery
      occlusion.
AB  - Local hypothermia induced by intra-arterial infusion of cold saline reduces brain
      injury in ischemic stroke. Administration of magnesium sulfate through the
      internal carotid artery is also known to reduce ischemic brain damage. The
      neuroprotective effects of combination therapy with local endovascular
      hypothermia and intra-carotid magnesium sulfate infusion has not been evaluated.
      The aim of the study was to determine whether infusion of intra-carotid cold
      magnesium offers neuroprotective efficacy superior to cold saline infusion alone.
      Sixty-eight Sprague-Dawley rats were subjected to 3 h of middle cerebral artery
      occlusion and were randomly divided into six groups: sham-operated group; stroke
      control group; local cold magnesium infusion group; local cold saline infusion
      group; local normothermic magnesium infusion group; and local normothermic saline
      infusion group. Before reperfusion, ischemic rats received local infusion or no
      treatment. Infarct volume, neurological deficit, and brain water content were
      evaluated at 48 h after reperfusion. Selective brain hypothermia (33-34  degrees
      C) was successfully induced by intra-carotid cold infusion. Local cold saline
      infusion and local cold magnesium infusion reduced the infarct volumes by 48 % (p
      < 0.001) and 65 % (p < 0.001), respectively, compared with stroke controls. Brain
      water content was decreased significantly in animals treated with local cold
      magnesium infusion. Furthermore, the rats given a local cold magnesium infusion
      had the best neurological outcome. Local normothermic infusion failed to improve
      ischemic brain damage. These data suggest that local hypothermia induced by intra
      carotid administration of cold magnesium is more effective in reducing acute
      ischemic damage than infusion of cold saline alone.

PMID- 22466875
TI  - Aortic dissection and malperfusion syndrome: a when, what and how-to guide.
AB  - Malperfusion syndrome is a complication of aortic dissection caused by branch
      vessel involvement and resulting in end-organ ischaemic dysfunction. Clinical
      diagnosis is mandatory, and imaging plays a critical role in confirmation and
      treatment planning. Radiologists must focus on detecting complications (findings
      of aortic dilation, rupture, organ ischaemia, etc.) and defining vascular
      compromise and associated malperfusion mechanisms. All these factors guide the
      multidisciplinary discussion concerning patient management and the suitability of
      endovascular treatment. Application of dedicated imaging protocols is mandatory
      in order to answer clinical and anatomical questions. Endovascular therapy has
      taken a predominant role in the therapeutic management of malperfusion syndrome
      with aortic fenestration, peripheral stenting and stent-grafting, all of which
      are procedures within the domain of expertise of current interventional
      radiologists. The purpose of this editorial is to present a when, what and how-to
      guide for all radiologists who encounter complicated aortic dissection.

PMID- 22466874
TI  - Clinical indications for cardiac computed tomography. From the Working Group of
      the Cardiac Radiology Section of the Italian Society of Medical Radiology (SIRM).
AB  - Cardiac computed tomography (CCT) has grown as a useful means in different
      clinical contexts. Technological development has progressively extended the
      indications for CCT while reducing the required radiation dose. Even today there
      is little documentation from the main international scientific societies
      describing the proper use and clinical indications of CCT; in particular, there
      are no complete guidelines. This document reflects the position of the Working
      Group of the Cardiac Radiology Section of the Italian Society of Radiology
      concerning the indications for CCT.

PMID- 22466876
TI  - Synthesis and electronic properties of a pentafluoroethyl-derivatized nickel
      pincer complex.
AB  - The synthesis of a bis(amino)amide nickel pincer complex bearing a perfluoroethyl
      ligand was effected by reaction of the corresponding nickel chloride complex with
      cesium fluoride and trimethyl(pentafluoroethyl)silane. Electrochemical
      experiments revealed that the oxidation of the LNi-C(2)F(5) complex occurs at the
      same potential as the LNi-Cl derivative, but reduction of the LNi-C(2)F(5)
      complex occurs at slightly more positive potentials. The similarity of the
      electrochemical data was corroborated by density functional theory (DFT), which
      predicts that the energies of the HOMOs (HOMO = highest occupied molecular
      orbital) and LUMOs (LUMO = lowest unoccupied molecular orbital) of the LNi
      C(2)F(5) and LNi-Cl complexes are equal in magnitude. DFT also revealed that the
      HOMOs of the bis(amino)amide nickel pincer complexes are primarily ligand in
      character, while the LUMOs are predominantly metal in character, supporting redox
      activity with this ligand.

PMID- 22466877
TI  - Host response: Attack is the best form of defence.

PMID- 22466880
TI  - Biological plaque control: novel therapeutic approach to periodontal disease.
AB  - Despite its important role in the control of periodontal disease, mechanical
      plaque control is not properly practiced by most individuals. Therefore,
      adjunctive chemical plaque control using chlorhexidine and antibiotics has also
      been suggested as an additional therapeutic strategy to augment mechanical plaque
      control. However, the additional effects of adjunctive antibiotic therapy are
      small, and topical chlorhexidine therapy is not without side effects. Given
      current limitations, new approaches for the control of biofilm are required. The
      new therapeutic approaches discussed in this review are divided into two
      categories: probiotics and vaccines. Probiotics is an interesting new field of
      periodontology research that aims to achieve biological plaque control by
      eliminating pathogenic bacteria. In addition, passive immunization using egg yolk
      antibody raised against periodontal pathogens may be an effective approach for
      the treatment of periodontitis. Further study to evaluate the possible effects of
      these biological plaque control methods against periodontal disease is warranted.

PMID- 22466881
TI  - Butyric acid induces apoptosis in both human monocytes and lymphocytes
      equivalently.
AB  - Short-chain fatty acids (SCFAs) are metabolites from anaerobic periodontopathic
      bacteria that induce apoptosis in immune cells such as lymphocytes, monocytes and
      macrophages. However, it remains unclear if SCFAs from pathogens induce apoptosis
      in monocytes/macrophages similarly with lymphocytes. This study investigated
      whether SCFAs-induced apoptosis is equal among the immunoregulatory cells. Cell
      apoptosis of the employed human cells was evaluated after treatment with culture
      supernatants from various periodontopathic bacteria or sodium butyrate. Apoptosis
      and viability were determined by detection of DNA fragmentation and using an MTS
      assay kit, respectively. Porphyromonas gingivalis and Fusobacterium nucleatum
      culture filtrates strongly induced apoptosis whereas Prevotella nigrescens and
      Prevotella intermedia culture filtrates failed to induce apoptosis in the THP-1
      and U937 human monocyte and macrophage cell lines. Healthy gingival fibroblasts
      and oral epithelial cells were resistant to all the culture filtrates. Gas-liquid
      chromatography detected butyric acid in P. gingivalis (21.0-34.0 mM) and F.
      nucleatum (36.0 mM) in culture filtrates, whereas, only trace levels were seen in
      P. nigrescens and P. intermedia. These results suggest that butyric acid produced
      by periodontopathic bacteria severely damages immunoregulatory cells in a
      consistent manner and, likewise, could be involved in mediating periodontal
      chronic inflammation.

PMID- 22466878
TI  - The type II secretion system: biogenesis, molecular architecture and mechanism.
AB  - Many gram-negative bacteria use the sophisticated type II secretion system (T2SS)
      to translocate a wide range of proteins from the periplasm across the outer
      membrane. The inner-membrane platform of the T2SS is the nexus of the system and
      orchestrates the secretion process through its interactions with the periplasmic
      filamentous pseudopilus, the dodecameric outer-membrane complex and a cytoplasmic
      secretion ATPase. Here, recent structural and biochemical information is reviewed
      to describe our current knowledge of the biogenesis and architecture of the T2SS
      and its mechanism of action.

PMID- 22466882
TI  - Inhibitory activity of Aloe vera gel on some clinically isolated cariogenic and
      periodontopathic bacteria.
AB  - Aloe vera is a medicinal plant with anti-inflammatory, antimicrobial,
      antidiabetic and immune-boosting properties. In the present study we investigated
      the inhibitory activities of Aloe vera gel on some cariogenic (Streptococcus
      mutans), periodontopathic (Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis) and an opportunistic periodontopathogen (Bacteroides fragilis)
      isolated from patients with dental caries and periodontal diseases. Twenty
      isolates of each of these bacteria were investigated for their sensitivity to
      Aloe vera gel using the disk diffusion and microdilution methods. S. mutans was
      the species most sensitive to Aloe vera gel with a MIC of 12.5 ug/ml, while A.
      actinomycetemcomitans, P. gingivalis, and B. fragilis were less sensitive, with a
      MIC of 25-50 ug/ml (P < 0.01). Based on our present findings it is concluded that
      Aloe vera gel at optimum concentration could be used as an antiseptic for
      prevention of dental caries and periodontal diseases.

PMID- 22466883
TI  - Reduced production of polymeric immunoglobulin receptor in murine dextran sodium
      sulfate-induced colitis.
AB  - Polymeric immunoglobulin receptor (pIgR) plays an intrinsic role in protecting
      the intestinal tract from invading pathogens. In the present study, we observed a
      decrease in pIgR in colon lysate from mice with dextran sodium sulfate (DSS)
      colitis. A decrease in pIgR was detected in both mRNA and protein levels.
      Histologic examinations revealed marked destruction of intestinal epithelial
      cells (IECs), and only a small number of regenerating IECs expressed pIgR. These
      results suggest that the decrease in pIgR was due to the destruction of IECs.
      Because activation of toll-like receptor 3 slows the progression of DSS colitis,
      we injected polyriboinosinic: polyribocytidylic acid (poly I:C) intraperitoneally
      and observed the correlation between pIgR level and severity of DSS colitis. Poly
      I:C markedly decreased progression of DSS colitis, and pIgR levels significantly
      recovered. Furthermore, we found that expressions of IFN-gamma and TNF-alpha were
      higher in DSS colitis. These results indicate that the decrease in pIgR was not
      compensated for by increased expression of these cytokines. In sum, our findings
      show that pIgR levels vary according to the severity of DSS colitis and that
      these changes might be useful as a biomarker of the severity of inflammatory
      bowel disease.

PMID- 22466885
TI  - Effect of surface treatment on bond strength between an indirect composite
      material and a zirconia framework.
AB  - The present study evaluated the effect of various surface treatments for zirconia
      ceramics on shear bond strength between an indirect composite material and
      zirconia ceramics. In addition, we investigated the durability of shear bond
      strength by using artificial aging (20,000 thermocycles). A total of 176 Katana
      zirconia disks were randomly divided into eight groups according to surface
      treatment, as follows: group CON (as-milled); group GRD (wet-ground with 600-grit
      silicon carbide abrasive paper); groups 0.05, 0.1, 0.2, 0.4, and 0.6 MPa
      (airborne-particle abrasion at 0.05, 0.1, 0.2, 0.4, and 0.6 MPa, respectively);
      and group HF (9.5% hydrofluoric acid etching). Shear bond strength was measured
      at 0 thermocycles in half the specimens after 24-h immersion. The remaining
      specimens were subjected to 20,000 thermocycles before shear bond strength
      testing. Among the eight groups, the 0.1, 0.2, 0.4, and 0.6 MPa airborne-particle
      abraded groups had significantly higher bond strengths before and after
      thermocycling. The Mann-Whitney U-test revealed no significant difference in
      shear bond strength between 0 and 20,000 thermocycles, except in the 0.2 MPa
      group (P = 0.013). From the results of this study, use of airborne-particle
      abrasion at a pressure of 0.1 MPa or higher increases initial and durable bond
      strength between an indirect composite material and zirconia ceramics.

PMID- 22466884
TI  - Melan-A/Mart-1- or HMB-45-positive melanocytes are not present in calcifying
      cystic odontogenic tumors (calcifying odontogenic cysts): a study in 13 Caucasian
      patients.
AB  - Melanin pigment and melanocytes may be found in odontogenic cysts and tumors,
      particularly calcifying cystic odontogenic tumor (CCOT). In the present study we
      investigated the immunohistochemical expression of the Melan-A/Mart-1 and HMB-45
      antigens in 13 Caucasians patients with CCOT. Melan-A/Mart-1- and HMB-45-positive
      melanocytes were not seen in any of the cases. Our findings are in agreement with
      the assumption that pigmentation in odontogenic lesions may be a racial
      phenomenon.

PMID- 22466886
TI  - Role of CTGF/CCN2 in reparative dentinogenesis in human dental pulp.
AB  - Connective tissue growth factor/CCN family 2 (CTGF/CCN2) has been considered to
      participate in tooth development. To date, the expression and role of CTGF/CCN2
      in reparative dentinogenesis have been unclear. Our previous study revealed that
      matrix metalloproteinase-3 (MMP-3) stimulates cell migration via CTGF/CCN2
      expression and secretion in human dental pulp cells, and that this is dependent
      on dynamin-related endocytosis and independent of protease activity. The
      objective of the present study was to determine the expression of CTGF/CCN2 in
      reparative dentin in human carious teeth and to examine the effect of CTGF/CCN2
      on mineralization in cultured human dental pulp cells. Minimal expression of
      CTGF/CCN2 was evident in odontoblasts subjacent to the dentin-pulp junction in
      healthy teeth, whereas strong expression was detected in odontoblast-like cells
      lining the reparative dentin subjacent to dental caries. In human dental pulp
      cells, CTGF/CCN2 promoted mineralization but failed to induce proliferation,
      suggesting that this molecule has the ability to induce the differentiation of
      human dental pulp cells. Taken together, the data suggest that CTGF/CCN2 is
      likely involved in reparative dentinogenesis through formation of hard tissue in
      human carious teeth.

PMID- 22466887
TI  - Influence of metal artifacts on in vivo micro-CT for orthodontic mini-implants.
AB  - This study aimed to show the effects of metal artifacts on the in vivo micro-CT
      of mini-implants by measuring bone volume. We drilled a hole in the cortical bone
      of a rat tibia and embedded a titanium orthodontic mini-implant (diameter, 1.5
      mm) in the hole. Twelve individually weighed hydroxyapatite grains (HA grains)
      were placed around the implant either by one dentist (method 1) or separately by
      12 dentists (method 2). In vivo micro-CT was used to scan the model after
      placement of each grain to measure increases and decreases in bone volume voxel
      number. The subtracted bone voxel volume increased with HA weight in both
      methods. Simple linear regression analysis showed a significant correlation
      between weight and volume in both methods (method 1: regression coefficient:
      516.502, P < 0.05; method 2: regression coefficient: 4837.432, P < 0.05). Metal
      artifacts did not appear to influence measurements of bone volume, although
      further studies are required to determine the effect of thicker implants.

PMID- 22466888
TI  - Discovery of putative salivary biomarkers for Sjogren's syndrome using high
      resolution mass spectrometry and bioinformatics.
AB  - The purpose of the current study was to determine if saliva contains biomarkers
      that can be used as diagnostic tools for Sjogren's syndrome (SjS). Twenty seven
      SjS patients and 27 age-matched healthy controls were recruited for these
      studies. Unstimulated glandular saliva was collected from the Wharton's duct
      using a suction device. Two ul of salvia were processed for mass spectrometry
      analyses on a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal
      time of flight (MALDI O-TOF) mass spectrometer. Raw data were analyzed using
      bioinformatic tools to identify biomarkers. MALDI O-TOF MS analyses of saliva
      samples were highly reproducible and the mass spectra generated were very rich in
      peptides and peptide fragments in the 750-7,500 Da range. Data analysis using
      bioinformatic tools resulted in several classification models being built and
      several biomarkers identified. One model based on 7 putative biomarkers yielded a
      sensitivity of 97.5%, specificity of 97.8% and an accuracy of 97.6%. One
      biomarker was present only in SjS samples and was identified as a proteolytic
      peptide originating from human basic salivary proline-rich protein 3 precursor.
      We conclude that salivary biomarkers detected by high-resolution mass
      spectrometry coupled with powerful bioinformatic tools offer the potential to
      serve as diagnostic/prognostic tools for SjS.

PMID- 22466889
TI  - Activation-induced cytidine deaminase mRNA expression in oral squamous cell
      carcinoma-derived cell lines is upregulated by inflammatory cytokines.
AB  - Activation-induced cytidine deaminase (AID) induces cytosine deamination to
      generate somatic hypermutation and class switch recombnation in immunoglobulin
      genes. AID expression is upregulated by inflammatory cytokines such as interferon
      gamma and tumor necrosis factor (TNF)-alpha, which in turn induce p53 mutations
      in inflammatory or cancer cells. In this study, the effects of growth factors,
      cytokines or sodium butyrate on AID mRNA expression were examined in human OSCC
      derived cells using real-time RT-PCR. Expression of AID mRNA was detected in OSCC
      cells and the expression was increased by EGF, TNF-a, or sodium butyrate. These
      results suggest that aberrant AID expression may play an important role in the
      dysplasia-carcinoma sequence in the oral cavity.

PMID- 22466890
TI  - Prevalence of Porphyromonas gingivalis fimA genotypes in Japanese children.
AB  - Porphyromonas gingivalis FimA fimbriae have been classified into 6 genotypes
      (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial
      subunits. We investigated the prevalence of fimA genotype in Japanese children.
      Dental plaque specimens were obtained from 400 subjects (age; 2 to 15 years),
      including 134 with healthy gingiva, 239 with gingivitis and 27 with
      periodontitis, and then analyzed by polymerase chain reaction. P. gingivalis was
      detected in 1.5%, 10.0% and 29.6% of these subjects, respectively. Significant
      differences were observed with regard to P. gingivalis infection among the groups
      [chi-squared analysis: gingivitis vs. healthy, P < 0.01, odds ratio (OR) = 7.4;
      periodontitis vs. healthy, P < 0.001, OR = 27.8]. In P. gingivalis-positive
      subjects with periodontitis, the most prevalent fimA types were type Ib/type II
      combination (37.5%) and type IV (37.5%), followed by type II (25.0%), while type
      IV (33.3%) and type II (29.2%) were most often detected in those with gingivitis.
      Our results suggest that the presence of P. gingivalis is associated with
      periodontal diseases, and that the type II, IV and Ib/II combination are the most
      common among fimA genotypes.

PMID- 22466891
TI  - Prevalence of oral mucosal disorders in institutionalized and non
      institutionalized psychiatric patients: a study from AVBR Hospital in central
      India.
AB  - Dental treatment is reported to be the greatest unattended health need of people
      with a disability. The aim of the present study was therefore to quantify the
      prevalence of oral diseases with a psychosomatic component (recurrent aphthous
      stomatitis, burning mouth syndrome, and oral lichen planus) in psychiatric
      patients and to screen these patients for any other oral disorders, so that
      better care could be provided. In this cross-sectional, single-assessment study,
      150 psychiatric patients were evaluated for presence of oral disorders. They were
      screened based on their socio-demographic profiles, clinical profile, and
      standardized psychiatric scales. The prevalence of recurrent aphthous stomatitis
      (RAS), burning mouth syndrome (BMS), and oral lichen planus (OLP) was 19.33%(29
      patients), 20.66% (31 patients) and 5.33% (8 patients), respectively, amongst all
      psychiatric patients. The prevalence of burning mouth syndrome was much higher in
      patients taking psychiatric medications (25%) than in drug-naive patients. On
      screening for other oral disorders, 35.33% of psychiatric patients had at least
      one other such disorder. We concluded that this patient group experiences a
      considerable burden of occult oral disorders necessitating thorough oral care. We
      also described the possible causes of the higher prevalence of oral disorders in
      psychiatric patients.

PMID- 22466892
TI  - Analysis of the molecular structure of human enamel with fluorosis using micro
      Raman spectroscopy.
AB  - The aim of this study was to analyze the molecular structure of enamel with
      fluorosis using micro-Raman spectroscopy and compare it with that of healthy
      enamel. Eighty extracted human molars were classified into four fluorosis groups
      according to the Thylstrup-Fejerskov Index (TFI) [TFI: 0, Healthy enamel; 1-3,
      mild; 4-5, moderate; 6-9, severe fluorosis]. All samples were analyzed by micro
      Raman spectroscopy. The integral areas of nu(1) (960 cm(-1)) phosphate peak as
      well as B-type carbonate peak (1070 cm(-1)) were obtained to analyze structural
      differences among the specimens. Although the differences were not statistically
      significant (P > 0.05), the mean of integral areas of nu(1) phosphate peak among
      groups indicated greater mineralization in the severe fluorosis group. However,
      there were statistically significant differences in the intensities, and the
      integral areas of B-type carbonate peak among groups (P < 0.05). Therefore,
      mineralization of the carbonate peak at 1070 cm(-1) decreased significantly in
      fluorotic groups, suggesting that carbonate ions are easily dissolved in the
      presence of fluoride. Although structurally fluorotic teeth are not more
      susceptible to dental caries, serious alteration in its surface topography may
      cause retention of bacterial plaque and formation of enamel caries. Micro-Raman
      spectroscopy is a useful tool for analyzing the molecular structure of healthy
      and fluorotic human enamel.

PMID- 22466893
TI  - Qualitative evaluation of two endodontic obturation techniques: tapered single
      cone method versus warm vertical condensation and injection system: an in vitro
      study.
AB  - Forty two single-rooted teeth, prepared with the Mtwo system, were divided into
      three groups based on the filling method: control, "Single-cone" (n = 20) (Mtwo
      gutta-percha single-cone tapered according to the diameter, length and conicity
      of the preparation) and "Combined system" (n = 20) (BeeFill 2in1). The parameters
      studied were apical leakage, gutta-percha adjustment, number of voids,
      presence/absence of sealer, root canal morphology, residual fragments, and
      filling of lateral/accessory canals. A dye penetration test was carried out
      (methylene blue). The teeth were embedded in resin, cut transversally and
      observed. The data were analyzed with non-parametric Mann-Whitney and Spearman
      tests. Comparative tests between the two groups showed that the "Combined system"
      was superior in terms of apical leakage (P < 0.01), gutta-percha adjustment (P <
      0.05) and filling of lateral/accessory canals (P < 0.05). There were
      statistically significant correlations between master cone adjustment and root
      canal morphology (P < 0.01) in the "Single-cone" group. In the "Combined system"
      group, a relation was observed between the voids and root canal morphology (P <
      0.05) and between voids and residual fragments (P < 0.05). The quality of
      obturation with warm gutta-percha was better than that of the tapered single-cone
      technique. Root canal morphology influences gutta-percha adjustment. Residual
      fragments on the root canal reduce sealing ability.

PMID- 22466894
TI  - Immunohistochemical expression of MMP-9 and VEGF in squamous cell carcinoma of
      the tongue.
AB  - Squamous cell carcinomas (SCCs) account for approximately 95% of all oral
      malignant neoplasms and for about 38% of all malignant head and neck tumors,
      especially affecting the tongue and lips. The aim of this study was to evaluate
      the immunohistochemical expression of MMP-9 and VEGF in oral SCC according to the
      occurrence of metastasis. Eighteen cases of tongue SCC without metastases and 17
      cases of tongue SCC with metastases were subjected to immunohistochemical
      methods. High immunohistochemical expression of MMP-9 and VEGF by neoplastic
      cells and stroma was observed in tongue SCCs at the invasion front. Metastatic
      tumors tended to express higher levels of MMP-9 and VEGF than non-metastatic
      tumors, but the difference was not significant (P > 0.05). Spearman's correlation
      test showed no significant correlation between VEGF-immunopositive vessels and
      metastasis (P > 0.05). The present results demonstrate the importance of the
      expression of MMP-9 and VEGF for the development of SCC of the tongue. However,
      no significant association was observed between the overexpression of MMP-9 or
      VEGF and the presence of metastases.

PMID- 22466895
TI  - Use of the Arabic version of Oral Health Impact Profile-14 to evaluate the impact
      of periodontal disease on oral health-related quality of life among Jordanian
      adults.
AB  - We used the short-form of the Oral Health Impact Profile (OHIP-14) to assess the
      impact of periodontal diseases on the quality of life of Jordanian adults. A
      systematic random sample of 400 individuals was selected from patients referred
      to the periodontics clinic at the Dental Teaching Center in Irbid, Jordan. Those
      willing to participate were examined by specifically trained dentists and
      requested to complete the Arabic short-form version of the OHIP-14 questionnaire.
      Multivariate analysis of differences in OHIP-14 subscales among the periodontal
      disease groups was conducted using the general linear model multivariate
      procedure. This study included 400 adults (164 men and 236 women) aged between 18
      and 60 years, with a mean (SD) of 36.7 (11.9) years. Of the 400 participants,
      41.8% had chronic gingivitis, 19.8% had mild periodontitis, 23.3% had moderate
      periodontitis, and 15.3% had severe periodontitis. "Fairly often" or "very often"
      was reported for one or more items of the OHIP-14 by fewer than one-third of
      patients with gingivitis (32.9%) or mild periodontitis (31.6%), by about one-half
      of patients with moderate periodontitis (53.8%), and by about two-thirds of those
      with severe periodontitis (63.9%). There was a statistically significant
      association between the severity of periodontal disease and OHIP-14 scores (P <
      0.05). Severe chronic periodontitis had a significantly greater impact on quality
      of life, specifically with regard to physical pain and physical disability (P <
      0.05). Physical pain and physical disability were the dimensions most affected,
      and all OHIP-14 scores were significantly associated with severity of periodontal
      disease after adjusting for common confounders.

PMID- 22466896
TI  - Depth of cure and hardness of indirect composite materials polymerized with two
      metal halide laboratory curing units.
AB  - The purpose of this study was to evaluate the depth of cure and Knoop hardness of
      indirect composite materials polymerized with different laboratory curing units.
      Five composite materials designed for fixed restoration veneer (Artglass,
      Ceramage, Epricord, Prossimo, and Solidex) were filled into a cylindrical mold
      and then light-exposed by using the respective proprietary laboratory curing unit
      or two metal halide curing units (Hyper LII and Twinkle X). Depth of cure was
      determined by a scraping technique, as described in ISO 4049. Composites also
      underwent Knoop hardness testing after immersion in water. The results (n = 5)
      were analyzed with the Kruskal-Wallis test and Dunn's multiple comparison test.
      For three materials (Prossimo, Artglass, and Epricord), depth of cure after
      polymerization with the Twinkle X unit was greater than that after polymerization
      with the respective proprietary units. For the Ceramage and Artglass materials,
      the Twinkle X unit resulted in the highest Knoop hardness number (KHN), whereas,
      for the Prossimo material, the Hyper LII unit resulted in the highest KHN. The
      metal halide units were effective in enhancing the post-polymerization properties
      of specific composite materials while reducing exposure time.

PMID- 22466897
TI  - Treatment of perforating internal root resorption with MTA: a case report.
AB  - Endodontic treatment of teeth with perforating internal root resorption
      represents a clinical challenge. In most cases, extraction of the tooth and
      subsequent replacement with an osseointegrated implant is indicated. Presented
      herein is a case report of a maxillary lateral incisor with advanced perforating
      internal root resorption in the middle third of the root and the presence of a
      sinus tract. Mineral Trioxide Aggregate (MTA) was used with the aid of a surgical
      microscope in order to fill the resorption area after conventional root canal
      therapy of the apical segment. At the follow-up after 11 years and 8 months, the
      patient was clinically asymptomatic and the sinus tract had disappeared. The
      radiographic examination and computerized tomography indicated periodontal bone
      repair.

PMID- 22466898
TI  - Concrescence of permanent maxillary second and third molars: case report of non
      surgical root canal treatment.
AB  - Concrescence is a rare developmental anomaly with an overall incidence of 0.8% in
      the permanent dentition. While many case reports describe the treatment of
      concrescence with extraction, there are few reports of non-surgical root canal
      treatment (NSRCT), due to the atypical root form, canal morphology, and technical
      difficulties involved in concrescence. This unique case report describes a
      technical modification of NSRCT that can retain joined posterior maxillary teeth
      to maintain natural posterior occlusion without surgical intervention or dental
      implants, thereby avoiding the risk of damage to a large portion of the alveolar
      bone near the maxillary sinus.

PMID- 22466899
TI  - Role of t-tubules in the control of trans-sarcolemmal ion flux and intracellular
      Ca2+ in a model of the rat cardiac ventricular myocyte.
AB  - The t-tubules of mammalian ventricular myocytes are invaginations of the surface
      membrane that form a complex network within the cell, with restricted diffusion
      to the bulk extracellular space. The trans-sarcolemmal flux of many ions,
      including Ca(2+), occurs predominantly across the t-tubule membrane and thus into
      and out of this restricted diffusion space. It seems possible, therefore, that
      ion concentration changes may occur in the t-tubule lumen, which would alter ion
      flux across the t-tubule membrane. We have used a computer model of the
      ventricular myocyte, incorporating a t-tubule compartment and experimentally
      determined values for diffusion between the t-tubule lumen and bulk extracellular
      space, and ion fluxes across the t-tubule membrane, to investigate this
      possibility. The results show that influx and efflux of different ion species
      across the t-tubule membrane are similar, but not equal. Changes of ion
      concentration can therefore occur close to the t-tubular membrane, thereby
      altering trans-sarcolemmal ion flux and thus cell function, although such changes
      are reduced by diffusion to the bulk extracellular space. Slowing diffusion
      results in larger changes in luminal ion concentrations. These results provide a
      deeper understanding of the role of the t-tubules in normal cell function, and
      are a basis for understanding the changes that occur in heart failure as a result
      of changes in t-tubule structure and ion fluxes.

PMID- 22466900
TI  - The interrelationship of mycophagous small mammals and ectomycorrhizal fungi in
      primeval, disturbed and managed Central European mountainous forests.
AB  - Small forest dwelling mammals are considered to be major consumers and vectors of
      hypogeous ectomycorrhizal (ECM) fungi, which have lost the ability of active
      spore discharge. Fungal spore dispersal by mycophagy is deemed an important
      process involved in forest regeneration, resilience and vitality, primarily based
      on evidence from Australia and the Pacific Northwestern USA, but is poorly known
      for Central European mountainous forests thus far. Small mammal mycophagy was
      investigated by live trapping and microscopical analysis of faecal samples. All
      small mammal species recorded (Myodes glareolus, Microtus agrestis, Pitymys
      subterraneus, Apodemus spp., Glis glis, Sorex spp.) had ingested spores of ECM
      fungi, albeit in varying amounts. My. glareolus was found to be the most
      important vector of ECM fungal spores, both in quantity and diversity. Species of
      the genus Sorex seem to play a hitherto underestimated role as dispersers of
      fungal spores. Glis glis is likely to be an important vector owing to its large
      home range. Hypogeous ECM basidiomycetes accounted for most spores found in the
      faecal samples. The frequency of various genera of hypogeous ECM ascomycetes and
      ECM epigeous fungi was much lower. Comparison with null models indicated a non
      random structure of the mycophagy network similar to other mutualistic bipartite
      networks. Mycophagy can be considered (1) to contribute to nutrition of small
      forest mammals, (2) to play a pivotal role for forest regeneration and
      functioning by providing mycorrhizal inoculum to tree seedlings and (3) to be
      vital for reproduction and diversity of the still poorly known hypogeous fungi.

PMID- 22466901
TI  - Diarylprolinol in an asymmetric aldol reaction of an alpha-alkyl-alpha-oxo
      aldehyde as an electrophile.
AB  - The direct aldol reaction of an alpha-alkyl-alpha-oxo aldehyde was catalyzed by
      trifluoromethyl-substituted diarylprolinol 1 to afford a gamma-oxo-beta-hydroxy
      alpha-substituted aldehyde in good yield with excellent anti-selectivity and
      excellent enantioselectivity.

PMID- 22466902
TI  - Low back pain: do the right thing and do it now.

PMID- 22466903
TI  - Results of liver transplantation in the treatment of Budd-Chiari syndrome.
AB  - BACKGROUND: Budd-Chiari syndrome (BCS) is a rare disorder which can lead to liver
      failure. It arises from an occlusion of small vessels and/or thrombosis of the
      major hepatic veins. Polycythemia vera is believed to be one of the most common
      factors causing BCS. In cases not responding to other measures, liver
      transplantation may be a successful method of radical treatment. The purpose of
      this study was to assess the value and results of liver transplantation in the
      treatment of Budd-Chiari syndrome. MATERIAL/METHODS: This retrospective study
      included all the cases of LTx (liver transplantation) performed because of BCS in
      the Department of General, Transplant and Liver Surgery, Medical University of
      Warsaw and it covered the period from 2000 to 2009. Twenty-four patients (8 men,
      16 women) with the average age of 33 +/- 11 presented with BCS, 6 patients (25%)
      underwent previous surgical therapy, 2 patients were treated by mesocaval "H"
      anastomosis (portosystemic shunts) and 4 patients received TIPSS (transjugular
      intrahepatic portosystemic shunt) prior to LTx. Polycythemia vera was an
      underlying risk factor in 11 cases. Two patients needed early retransplantation
      (re-LTx). In immunosuppressive therapy, schema with glucocorticosteroids and FK
      506 predominated. RESULTS: Four cases of bleeding to peritoneal cavity requiring
      surgical intervention were observed; 3 patients died in the early post-transplant
      period due to multiorgan failure and 1 late death occurred because of internal
      causes. Actual survival rate was 83% at 5 years. CONCLUSIONS: In the late stage,
      Budd-Chiari syndrome should be considered as an indication for liver
      transplantation, especially when other measures such as porto-systemic shunts are
      scarce and ineffective.

PMID- 22466904
TI  - Intestinal ischemia-reperfusion injury - the histopathological status of remote
      vital organs in acute and subacute phases.
AB  - BACKGROUND: Improvement of graft recovery and function follows current trends in
      intestinal transplantation; however, the alteration of remote organs (RO)
      predicts complicated systemic rejection. This study was conceived to describe the
      histopathological status of RO arising in both acute and subacute stages after
      intestinal ischemia-reperfusion injury (IIR) injury. MATERIAL/METHODS: Wistar
      rats (n=54) were divided into 7 experimental groups (n=7 each). All the animals
      were subjected to 60 min mesenteric ischemia and subsequently to reperfusion 2 h,
      4 h, 24 h, 72 h, 10 days, 20 days and 30 days following the groups IR2 h, IR4 h,
      IR24 h, IR72 h, IR10 d, IR20 d and IR30 d. As a control group (S; n=5) sham
      operated animals were used. Histopathological scores (HPS) were evaluated in
      biopsies of the right kidney, heart and colon ascendens. RESULTS: Statistically
      significant increase in kidney HPS was seen during reperfusion, with the peak in
      IR4h group (p<0.01). Thereafter, improved morphology was observed; however,
      increased HPS was seen even in the subacute stage, and significant deterioration
      of HPS up to 10 days of reperfusion was detected (p<0.05). Heart biopsies also
      showed statistically increased HPS value in IR4h group (p<0.05). Intact
      morphology of the colon was detected in all reperfusion periods. CONCLUSIONS: IIR
      causes a systemic reaction affecting RO. The peak of alteration for kidney and
      heart morphology was induced by 60 min of ischemia followed by 4 h of
      reperfusion. Thereafter, improved morphology was observed, although latent
      persistence of histopathological changes was seen even in the subacute stage. The
      colon remained intact during the whole experiment despite its anatomical
      proximity, confirming its high immunological capacity.

PMID- 22466905
TI  - Right ventricular function during orthotopic liver transplantation: three
      dimensional transesophageal echocardiography and thermodilution.
AB  - BACKGROUND: Right ventricular (RV) function is an important aspect of anesthesia
      management during orthotopic liver transplantation (OLT). Because of its
      geometrical complexity, assessment of RV dimensions with transesophageal
      echocardiography (TEE) is a difficult task. The aim of this prospective single
      site study was to investigate the feasibility of intraoperative assessment of RV
      parameters based on reconstructive three-dimensional (3D) TEE and to compare the
      measurements to thermodilution-derived values acquired with a modified pulmonary
      artery catheter. MATERIAL/METHODS: Measurements were performed at four different
      time points during 30 OLT with 3D-TEE. At the same time comparative values of RV
      parameters were acquired with a fast-response thermistor pulmonary artery
      catheter. RESULTS: 3D reconstruction was feasible in all patients. RV dimensions
      measured with 3D-TEE averaged 119.4 ml (+/- 38.5 ml) for enddiastolic and 68.9 ml
      (+/- 27.7 ml) for endsystolic volumes. The RV ejection fraction was 42.2% (+/-
      9.3%). The volumes obtained by thermodilution were 263.7 ml (+/- 64.5 ml)
      enddiastolic and 159.3 ml (+/- 47.5 ml) endsystolic, both significantly greater
      than by 3D-TEE, and the ejection fraction was found to be 39.5% (+/- 8.4%). No
      correlation was found between the volumes or the function determined by either
      method. CONCLUSIONS: Reconstructive 3D-TEE is a viable technique during OLT and
      leads to plausible RV parameters. However, no correlation was found with
      simultaneous measurements or parameters performed with thermodilution. However,
      based on our data cardiac output measurements by thermodilution appear
      reasonable. Due to both lack of agreement with 3D-TEE and extraordinary high RV
      volumes the question about the most valuable monitoring technique of RV
      dimensions and function during OLT can not finally be answered.

PMID- 22466906
TI  - The usefulness of a high-speed 3D-image analysis system in pediatric living donor
      liver transplantation.
AB  - BACKGROUND: Since March 2010, we have used a high-speed 3D-image analysis system
      (SYNAPSE VINCENT) to calculate the graft volume in living donor liver
      transplantation (LDLT) to replace CT volumetry. The SYNAPSE VINCENT is capable of
      extracting each vessel territory in the liver and displaying 3D images simply,
      quickly, and accurately. Therefore, we report here the usefulness of the SYNAPSE
      VINCENT in pediatric LDLTs in overcoming issues with perfusion area of hepatic
      venous tributaries in monosegmental grafts. MATERIAL/METHODS: The SYNAPSE VINCENT
      was used in three pediatric patients. In two of these cases, the possibility of
      monosegmental grafts was assessed when calculating graft volumetry of segment
      III. RESULTS: The graft recipient weight ratio (GRWR) with graft volumetry
      measurements of the left lateral segment were 1.8-5.6%. GRWR of segment III were
      2.3 and 2.0%. Since donor V2, venous branch to segment II and V3, venous branch
      to segment III were independently branching in one case, the monosegmental graft
      could be evaluated preoperatively according to the venous perfusion. CONCLUSIONS:
      Graft volumetry using the SYNAPSE VINCENT was useful for planning the LDLT
      operative procedures, especially in infants possibly in need of monosegmental
      graft.

PMID- 22466907
TI  - Results of renal transplantation from expanded criteria deceased donors - a
      single-center experience.
AB  - BACKGROUND: Transplantation of kidneys retrieved from extended criteria donors is
      one of the options to expand the pool of available grafts, shorten the waiting
      time and increase the availability of this method of treatment. However, some
      factors (eg, donor age) may impair the results of transplantation.
      MATERIAL/METHODS: This study was a retrospective assessment of 327 patients who
      underwent renal transplants during the period 1995-2005, with kidneys harvested
      from expanded criteria donors (ECD) as defined by the United Network for Organ
      Sharing (UNOS). They formed 2 groups: group 1 (ECD - younger, n=255) consisted of
      recipients of kidneys obtained from donors aged 50-59 years; group 2 (ECD -
      older, n=72) consisted of patients who received kidneys from donors >= 60 years
      old. An analysis of the 1-, 3- and 5-year survival of grafts and patients and
      evaluation of graft function were performed. RESULTS: graft survival was
      significantly better in group 1 (ECD-younger) vs. group 2 (ECD-older), as was
      renal graft function. Survival 3 and 5 years after transplantation was 87.7% vs.
      81.9%, 73.1% vs. 66.6%, and 60.1% vs. 51.7%, respectively. Delayed graft function
      occurred significantly more frequently in group 2 (group 1 vs. group 2-28.8% vs.
      34.6%, p=0.0001). CONCLUSIONS: The transplantation of kidneys obtained from older
      donors fulfilling ECD definition is associated with shorter graft survival,
      deteriorated function and more frequent renal delayed graft function. However,
      this did not increase the mortality of recipients.

PMID- 22466908
TI  - A novel technique for suture-free repair of renal allograft rupture.
AB  - BACKGROUND: Renal allograft rupture (RAR) is a rare complication, but it can
      cause graft loss and be life-threatening. Surgical exploration and repair is
      essential for saving the kidney graft. The aim of this article is to describe a
      novel suture-free technique for management of RAR. MATERIAL/METHODS: Twenty-six
      RARs were diagnosed in 1851 kidney transplants from November 2002 to November
      2008. The study was divided into 2 groups: a suture group and a suture-free
      group. Twelve cases were treated in the suture group, whereas 14 were treated by
      the suture-free technique. In the suture-free group, absorbable thread was used
      to bundle the ruptured renal graft. For the suture group, autologous cubic
      muscular tissues or external oblique aponeurosis were used as pledgets. RESULTS:
      In the suture-free group all 14 grafts were rescued with creatinine (Cr) at 1.8
      +/- 0.62 mg/dl on discharge. In the suture group all 12 grafts were repaired
      successfully with Cr 1.9 +/- 0.63 mg/dl on discharge. The 1-, 3- and 5-year graft
      survival rate was 92.8%, 82.5%, 70.50%, respectively, in the suture-free group
      and 84.1%, 75.5%, 67.4%, respectively, in the suture group. The suture-free
      technique had shorter operation time, less blood transfusion and shorter hospital
      stay. CONCLUSIONS: The suture-free technique is a safe and effective technique
      for treatment of RAR, with advantages of shorter operating time, less blood loss
      and quicker recovery after surgery.

PMID- 22466909
TI  - Prevalence of arterial hypertension and the number and classes of
      antihypertensive drugs prescribed for patients late after kidney transplantation.
AB  - BACKGROUND: There are limitations of the use of several classes of
      antihypertensive drugs in patients after kidney transplantation (KTx), as well as
      contradictory opinions on their effects on progression of graft dysfunction. In
      this study we assessed the prevalence of arterial hypertension (HA) and the
      antihypertensive agents used by the patients long after KTx. MATERIAL/METHODS:
      This retrospective evaluation of the number and classes of antihypertensive drugs
      was based on medical records of 348 patients (140 F, 208 M; mean age 49 +/- 13
      years) late after KTx (mean time after KTx 78 +/- 43 months). The data were
      related to graft function. RESULTS: Ninety-three percent of patients after KTx
      required antihypertensive therapy. Only 8.7% were treated with 1 agent (mean eGFR
      65.1 +/- 27.4 ml/min), 26.3% received 2 drugs (eGFR 60.0 +/- 25.8 ml/min), 34.2%
      received 3 drugs (eGFR 55.5 +/- 23.4 ml/min), 20.1% received 4 drugs (eGFR 54.9
      +/- 24.9 ml/min), and 10.5% received >= 5 drugs (eGFR 45.9 +/- 22.0 ml/min). The
      number of antihypertensive medications increased along with the deterioration of
      graft function. Dihydropyridine calcium antagonists (CCB) were the most common
      class of drugs recommended to the patients after KTx (81%), followed by beta
      adrenergic antagonists (74.4%); alpha-antagonists (40.2%), angiotensin-converting
      enzyme inhibitors (38.7%), diuretics (34.1%), clonidine (17.8%) and angiotensin
      II receptor blockers (9.5%). CONCLUSIONS: HA is highly prevalent in KTx patients.
      Multidrug therapy is usually required for the treatment of HA in this population.
      Dihydropyridine CCB is the most common class of antihypertensive drugs used by
      them. Graft function is a determining factor in the number of antihypertensive
      agents.<br />

PMID- 22466910
TI  - Conversion from everolimus with low-exposure cyclosporine to everolimus with
      mycophenolate sodium maintenance therapy in kidney transplant recipients: a
      randomized, open-label multicenter study.
AB  - BACKGROUND: Data in kidney transplant recipients regarding elimination of
      calcineurin inhibitor (CNI) therapy from a de novo regimen based on low CNI
      exposure and an mTOR inhibitor are sparse, and restricted to CNI elimination
      within the first six months post-transplant. MATERIAL/METHODS: In a 12-month,
      randomized, multicenter, open-label study, kidney transplant patients who had
      received everolimus, low-exposure cyclosporine and corticosteroids from
      transplantation to month 12 (with proteinuria <1 g/24 h at month 12) were
      randomized to convert from cyclosporine to mycophenolate sodium 720 mg/day with
      increased everolimus exposure (6-10 ng/mL [CNI-free group], n=15) or continue
      unchanged (everolimus 3-8 ng/mL [CNI group], n=15). RESULTS: Median (range)
      baseline mGFR was 54 (21-87) mL/min and 37 (range 18-69) mL/min (p=0.053) in the
      CNI-free and CNI groups, respectively, compared to 56 (18-126) mL/min and 32 (12
      63) mL/min at month 12 (p=0.007). The between-group difference in change in mGFR
      from baseline to month 12 post-conversion (the primary endpoint) was -14.4 mL/min
      (95% CI -29.3 to 0.6 mL/min, p=0.059 [least squares mean]). Changes in serum
      creatinine and estimated GFR to month 12 were significantly in favor of CNI-free
      patients. One CNI patient experienced biopsy-proven acute rejection. Study drug
      was discontinued due to adverse events in one CNI-free patient (7%) and three CNI
      treated patients (20.0%). CONCLUSIONS: Elimination of CNI from a de novo regimen
      of everolimus with low-exposure CNI at one year post-transplant maintained
      efficacy and led to a non-significant but clinically relevant improvement in
      renal function, although patients numbers were low (n=30). Findings from this
      small study require confirmation in a larger controlled trial.

PMID- 22466911
TI  - Pharmacokinetic monitoring of mycophenolic acid in heart transplant patients:
      correlation the side-effects and rejections with pharmacokinetic parameters.
AB  - BACKGROUND: Mycophenolate mofetil is a commonly used immunosuppressant in heart
      transplantation but pharmacokinetic monitoring is not routinely done. We
      performed a prospective pilot multi-center trial in de-novo heart transplant
      recipients to evaluate the pharmacokinetics (PK) of mycophenolic acid (MPA) at
      multiple time points in the first year following transplant.<br />
      MATERIAL/METHODS: MPA trough and estimated area-under-the-curve (AUC) values were
      obtained at multiple visits from 21 enrolled patients. We attempted to correlate
      the side-effects and rejections with PK parameters.<br /> RESULTS: MPA AUC and
      trough levels increased modestly over 12 months with substantial inter and intra
      patient variability. Cardiac rejection was associated with low MPA AUC values
      with a threshold of <36.2 mg*h/L during the first two post-transplant weeks. A
      threshold of 2-weeks average MPA trough level of 1.43 mg/L provided a sensitivity
      82% and a specificity of 60%.<br /> CONCLUSIONS: Adequate MPA levels are
      associated with decreased risk of allograft rejection. For patients with
      Cyclosporine co-immunosuppression, we propose an MPA trough of 1.4 mg/L and an
      MPA AUC of 36 mg * h/L as threshold values for dose adjustments. We recommend
      monitoring MPA levels at 1, 2 and 4 weeks, 6 months, 1 year and whenever an
      unexplained side-effect or allograft rejection occurs. Additional MPA AUC
      measurements are recommended when trough levels do not explain the clinical
      picture.<br />

PMID- 22466912
TI  - Atorvastatin donor pre-treatment in a model of brain death and allogeneic kidney
      transplantation in rat.
AB  - BACKGROUND: The aim of the present study was to evaluate the effect of donor pre
      treatment with atorvastatin in a model of brain death followed by prolonged cold
      preservation and allogeneic kidney transplantation in rats. MATERIAL/METHODS:
      Donor rats were pre-treated with atorvastatin or vehicle 2 days prior to
      induction of brain death. After a brain death period of 6h kidneys were explanted
      and stored for 24 h at 4 degrees C in UW solution and transplanted into
      allogeneic recipients. Non brain dead rats treated with vehicle were ventilated
      for 6h prior to explantation and served as controls. Grafts were harvested after
      10 days. RESULTS: Donor treatment of brain dead organ donors with atorvastatin
      had no influence on renal histology (Banff score) or renal inflammation compared
      to vehicle treated brain dead rats 10 days after cold preservation and allogeneic
      transplantation. Grafts from brain dead organ donors showed severe signs of
      vasculopathy compared to grafts from non brain dead organ donors 10 days after
      prolonged cold preservation and allogeneic kidney transplantation. Kidneys
      harvested after brain death before cold preservation and allogeneic
      transplantation showed an increased infiltration of ED1 and MHCII positive cells
      compared to kidneys of non-brain dead animals (NBD). CONCLUSIONS: Atorvastatin
      donor pre-treatment of brain dead organ donors combined with 24h of cold
      preservation has no influence on graft rejection and infiltration with ED1 or
      MHCII positive cells in an allogeneic rat renal transplantation model. The
      detrimental combination of brain death and cold preservation might have overcome
      the possible protective effect of atorvastatin donor pre-treatment.

PMID- 22466913
TI  - BK virus replication following kidney transplant: does the choice of
      immunosuppressive regimen influence outcomes?
AB  - The increasing prevalence of BK virus nephropathy (BKVN) observed in recent
      years, with its consequent impact on kidney allograft survival rates, has focused
      attention on the relationship between immunosuppression regimens and risk of BK
      virus reactivation. The adoption of more potent immunosuppressive regimens over
      the last two decades, notably tacrolimus with mycophenolic acid and
      corticosteroids, appears to be associated with higher rates of BK activation.
      There is also evidence of a specific increase in risk for tacrolimus-based
      immunosuppression vs. cyclosporine, which in vitro data suggest may be at least
      partly due to differences in antiviral activity. Early concerns that mammalian
      target of rapamycin (mTOR) inhibitor use was associated with development of BKVN
      do not appear to have been borne out. Protocol-driven BK virus screening is
      recommended to facilitate early diagnosis and intervention, which primarily
      comprises the controlled reduction or discontinuation of immunosuppressive drugs.
      Although a consensus on the optimal strategy for immunosuppression modification
      is still lacking, early diagnosis of BK reactivation and pre-emptive modification
      of immunosuppression has resulted in a marked improvement in graft outcomes.
      Typically, intervention consists of reducing calcineurin inhibitor exposure
      before or after antimetabolite dose reduction, withdrawal of one agent from a
      triple therapy regimen, or switching between agents within a therapeutic class. A
      benefit for antiviral therapy is not yet confirmed. While more data are required,
      the current evidence base is adequate to justify routine screening with early
      modification of the intensity and nature of the immunosuppression regimen to
      reduce the toll of BKVN in the kidney transplant population.

PMID- 22466914
TI  - Hypertension in solid organ transplant recipients.
AB  - Hypertension (HT) is one of the most frequent complications of solid organ
      transplantation; about 70-90% of this population have high blood pressure or
      require antihypertensive therapy. Abnormal blood pressure is a potent non
      immunological risk factor directly related to patient and graft survival. The
      etiology of hypertension after orthotopic heart transplantation is multifactorial
      and varies depending on the time following transplantation. In the early period
      after transplantation, hypertension is generally related to intravascular volume
      expansion and persistently increased systemic vascular resistance. Other factors
      predominant in kidney allograft recipients include: donor age, donor familial
      history of hypertension, transplant renal artery stenosis, graft function, the
      recurrence or de novo appearance of glomerulonephritis in transplanted kidney,
      and post-biopsy arteriovenous fistula. In liver and heart transplantation,
      hypertension is mainly due to impaired kidney function, with all its
      consequences. Another contributing factor is immunosuppressive regimen based on
      calcineurin inhibitors and steroids. The management of post-transplant
      hypertension usually requests non-pharmacological and pharmacological treatment.
      In this review, the pathogenesis and treatment of post-transplant hypertension in
      solid organ transplantation is presented.

PMID- 22466915
TI  - Bariatric surgery as a bridge for kidney transplantation in obese subjects. Case
      report.
AB  - BACKGROUND: The epidemiological studies indicate that the problem of obesity and
      associated metabolic syndrome affects the steadily increasing population. The
      obesity also applies to the patients with the end-stage renal failure requiring
      renal replacement therapy. Morbid obesity is a contraindication to renal
      transplantation procedure. A significant excess weight greatly increases the
      waiting time for transplantation, increases the risk of surgical complications,
      including complications due to cardiovascular and metabolic disorders. The
      combination of these risk factors with the immunosuppressive therapy may worsen
      the symptoms associated with the renal failure, contribute to the deterioration
      of graft function, shorten the survival, and increase the risk of patient death.
      CASE REPORT: In this paper we described the first Polish case of kidney
      transplantation, in a patient after bariatric surgery. The patient was
      disqualified from kidney transplantation because of obesity and referred to our
      department for metabolic surgery and weight reduction before potential kidney
      transplantation. 10 months post the bariatric surgery patient was selected as a
      kidney transplant recipient from a deceased donor. Both procedures have been
      performed in this same center. CONCLUSIONS: Bariatric surgery procedures are safe
      and effective in patients with end-stage renal disease. Bariatric procedures may
      be considered as a procedural bridge for a group of morbidly obese patients with
      renal failure, allowing them to be qualified for transplantation.

PMID- 22466916
TI  - A brain dead woman, giving birth in the 23rd week of pregnancy, used as an organ
      donor: a case report.
AB  - BACKGROUND: Maternal brain death during pregnancy is an exceptional case when
      somatic support might be continued despite diagnosed death. There are only a few
      cases of maternal brain death during pregnancy reported in the literature and
      detailed data regarding the frequency of such cases are lacking. CASE REPORT: The
      case of a 40-year-old woman, diagnosed brain dead due to a subarachnoid and
      intracranial hemorrhage in the 21st week of pregnancy is presented. The patient
      was admitted to the neurosurgery department and then to the intensive care unit,
      where brain death was diagnosed. The medical team decided to perform a caesarean
      section, and a living female infant was delivered. After delivery, maternal
      kidneys were recovered and successfully transplanted. CONCLUSIONS: This
      challenging case indicates that prompt diagnosis of maternal brain death is
      required to facilitate decision-making regarding somatic support prolongation to
      save the life of the fetus, as well as to allow procurement of the maternal
      organs.

PMID- 22466917
TI  - Liver transplantation results in complete neurologic recovery from malignant
      hypertension secondary to fulminant hepatic failure: a case report.
AB  - BACKGROUND: Uncontrolled intracranial hypertension can lead to cerebral
      herniation and death in patients with acute liver failure. CASE REPORT: A 26-year
      old female was admitted for acute liver failure following inadvertent
      acetaminophen overdose. The pH on admission was 6.9. Her neurologic status
      precipitously deteriorated and she was listed for liver transplantation. An
      intracranial pressure (ICP) monitoring catheter was inserted, which revealed a
      pressure >60 mmHg. After neurointensive care treatment, ICP was lowered and an
      emergency left lobe living donor liver transplant was performed. Intraoperative
      management of the ICP, which rose to 80 mmHg during the explant phase, was
      achieved by therapy with barbiturates and hypothermia. After surgery, hepatic
      function improved initially, but 7 days post transplantation the graft showed
      signs of acute failure. The pathology report of a liver biopsy suggested acute
      rejection and liver retransplantation using a deceased donor liver was then
      carried out. The postoperative course was uneventful and the patient recovered
      completely without any residual neurologic deficits. CONCLUSIONS: This case
      states that favourable outcomes can result from sub-optimal starting points, and
      that the human brain has the ability to overcome extremely adverse conditions.
      Critical in this effort is the role of proper neuromonitoring which helps
      implement the appropriate treatment measures.

PMID- 22466918
TI  - Urgent liver transplantation for nevirapine-induced acute liver failure: report
      of a case and review of the literature.
AB  - BACKGROUND: Acute liver failure (ALF) due to antiretroviral treatment is a rare
      but a fatal complication in HIV-infected patients. Non-nucleoside retroviral
      transcriptase inhibitors are known to cause hepatotoxicity and exceptionally
      acute hepatic failure. CASE REPORT: We report a case of nevirapine-induced acute
      liver failure successfully managed with orthotopic liver transplantation (OLT).
      Antiretroviral therapy including raltegravir, zidovudine and abacavir was
      reintroduced 6 days after transplantation. No interaction with immunosuppressive
      agents was observed and the patient had a complete recovery. CONCLUSIONS: Urgent
      OLT should be considered in HIV patients with nevirapine-induced ALF because of
      the poor outcome despite intensive supportive conservative treatment. Concomitant
      use of highly active antiretroviral therapy (HAART) and immunosuppression could
      be feasible if treatment is performed cautiously.

PMID- 22466919
TI  - Amoxicillin/clavulanic acid-induced cholestatic liver injury after pediatric
      liver transplantation.
AB  - BACKGROUND: Amoxicillin/clavulanic acid-induced liver injury is a well recognized
      complication. Presentation and outcome may vary, which is related to individual
      liver maturity, genetic predisposition, enzyme heterogeneity, intensity of
      treatment, and drug interactions. In most cases withdrawing the drug is
      sufficient treatment; however, cases of progressive liver damage leading to liver
      transplantation have been reported. CASE REPORT: We present the case of an 8-year
      old patient after liver transplantation who developed drug induced liver injury
      (DILI) after amoxicillin/clavulanic acid treatment for upper respiratory tract
      infection. Jaundice appeared 2 days after cessation of treatment. Clinical
      presentation and liver biopsy were consistent with DILI. Because of rapidly
      increasing bilirubin levels, we used 3 boluses of methylprednisolone and
      ursodeoxycholic acid. The treatment reversed progression of the cholestasis and
      full recovery was achieved in 3 months. CONCLUSIONS: In most cases of DILI,
      withdrawing the toxic drug is sufficient treatment, but we must be aware of a
      possible fatal outcome in case of progressive cholestasis. Corticosteroids may
      have beneficial effects in these patients.<br />

PMID- 22466920
TI  - Kidney transplantation in Mongolia using effective and economical
      immunosuppression - a three-year experience.
AB  - Between August 2006 and August 2009, 34 ethnic Mongolians were the recipients of
      a kidney transplant at the Central Clinical Hospital in Ulaanbaatar, Mongolia. In
      31 of the operations the donor was either a sibling or parent. In 4 recipients
      the donors were 2 recently deceased accident victims following controlled cardiac
      arrest and after next of kin permission. All 4 recipients are alive with life
      supporting function. Appropriate legislation was passed in 2008. Thirty-one of
      the 34 recipients (91%) are alive. The 1-year patient and graft survival is 91%
      and 82%, respectively. In all cases, recipients received 1 dose of Campath 1
      preoperatively followed by monotherapy with either Cyclosporin or Tacrolimus. Due
      to the remote geographical location of some of the recipients, appropriate serum
      drug levels were difficult to monitor. Azathioprine was therefore added in the
      last 13 recipients. Except for acute rejection episodes, no patients received
      steroid therapy. There were 7 diagnosed and treated acute rejections in the 34
      recipients (21%). The mean annual cost of the immunosuppressive therapy period
      compared favorably with neighboring China and with costs in Spain. We conclude
      that the use of Campath 1 together with a non-steroid maintenance
      immunosuppressive regimen provides both economical and acceptable graft and
      patient survival in a developing country.<br />

PMID- 22466921
TI  - The effect of education on the attitude of medical students towards organ
      donation.
AB  - BACKGROUND: The persisting shortage of organs for transplantation could be
      reduced by increasing the willingness to donate organs. An appropriate education
      and a positive attitude of medical students and future physicians towards organ
      donation may have a positive impact on the attitudes of the general public.
      MATERIAL/METHODS: During the summer semester 2010 we conducted a voluntary
      educational intervention study concerning organ donation among medical students
      in the course of the main surgery lecture at the University of Essen, Germany.
      RESULTS: The survey comprised 94 questionnaires. At the beginning of the lecture
      there were 67% of organ donor card carriers among the students. An additional 20%
      imagined they might carry an organ donor card in the future. 37% needed more
      information regarding organ donation. After the lecture 13% were still not
      willing to carry an organ donor card in the future. 18% of the students required
      further information. 42% of the students rated their attitude towards organ
      donation to be influenced positively by the lecture, 57% of the students stated
      there was no influence. One student documented a negative influence by the
      lecture towards organ donation. CONCLUSIONS: Well-directed interventions are
      needed to sensitize young adults to the topic of organ donation. Better
      understanding of medical students and future physicians in the field of organ
      donation will help them to become disseminators for this important topic in our
      society.

PMID- 22466922
TI  - Malignancy after kidney transplantation.

PMID- 22466923
TI  - Differences in invasive fungal infections between liver and kidney transplant
      patients.

PMID- 22466924
TI  - Early nutrition impact on the insulin-like growth factor axis and later health
      consequences.
AB  - PURPOSE OF REVIEW: There is increasing interest in the role of insulin-like
      growth factor-I (IGF-I) in the relation between early growth and later risk of
      noncommunicable diseases (NCDs). This review presents and discusses a selection
      of recent publications on this topic. RECENT FINDINGS: Nutrition during pregnancy
      and in preterm infants has an influence on IGF-I. Breastfeeding is associated
      with lower IGF-I values and the effect of early protein intake was confirmed in a
      large intervention study. IGF-I levels are associated with early obesity, but the
      relation is complex and differs with age. Further studies and reviews support
      that there is a programming of the IGF axis, with higher levels during early life
      being associated with lower levels in adulthood, which is likely to influence the
      risk of NCDs later in life. SUMMARY: Recent studies support that IGF-I plays an
      important role in the complex association between early diet, growth and later
      health, but more studies are needed to better understand the role of IGF-I,
      especially in the early development of obesity. Studies with data on how IGF-I is
      influenced by early diet in studies of preterm infants and young children with
      undernutrition from low-income countries will be helpful in recommending optimal
      diets.

PMID- 22466925
TI  - Terminology in cancer cachexia:  importance and status.
AB  - PURPOSE OF REVIEW: This article reviews the current status of the definition of
      cancer cachexia, and comments on future initiatives to refine it and to use it as
      a foundation for a cancer cachexia classification system. RECENT FINDINGS: There
      has been a plethora of work by expert panels defining cachexia. Stemming from
      this work, an expert panel has published a definition of cancer cachexia and a
      three level staging system: precachexia, cachexia, and refractory cachexia.
      Colleagues in the cancer pain field have put forward a sophisticated pain
      classification system. Work to develop a similar classification system for
      cachexia is now commencing. Aside from improved communication, these efforts may
      also enable the oncology community to better appreciate the importance of cancer
      cachexia and to participate in interdisciplinary treatment programmes to combat
      cachexia. SUMMARY: The quest to determine the pathophysiology of cancer cachexia
      and to use this knowledge to identify patient subsets will further research.
      Equally important, the fruits of this endeavour will lead to a higher priority
      for addressing cachexia with consequent development of a multimodal approach to
      management.

PMID- 22466926
TI  - Oxidative stress and disuse muscle atrophy:  cause or consequence?
AB  - PURPOSE OF REVIEW: This review will discuss the evidence both for and against the
      concept that reactive oxygen species (ROS) play an important role in the
      regulation of inactivity-induced skeletal muscle atrophy. RECENT FINDINGS: It is
      well established that prolonged skeletal muscle inactivity causes muscle fiber
      atrophy and a decrease in muscle force production. This disuse-induced muscle
      atrophy is the consequence of a loss in muscle protein resulting from increased
      protein degradation and decreased protein synthesis. Recent studies suggest that
      oxidative stress can influence cell-signaling pathways that regulate both muscle
      protein breakdown and synthesis during prolonged periods of disuse. Specifically,
      it is feasible that increased ROS production in muscle fibers can promote
      increased proteolysis and also depress protein synthesis during periods of
      skeletal muscle inactivity. SUMMARY: Although it is established that oxidants can
      participate in the regulation of protein turnover in cells, there remains debate
      as to whether oxidative stress is required for disuse skeletal muscle atrophy.
      Nonetheless, based on emerging evidence we conclude that increased ROS production
      in skeletal muscles significantly contributes to inactivity-induced muscle
      atrophy.

PMID- 22466927
TI  - Muscle wasting:  a crosstalk between protein synthesis and breakdown signalling.

PMID- 22466928
TI  - Survival:  the relevant primary outcome for nutrition therapy in cancer patients.

PMID- 22466929
TI  - Therapeutic potential of apixaban in the prevention of venous thromboembolism in
      patients undergoing total knee replacement surgery.
AB  - Anticoagulant prophylaxis for preventing venous thromboembolism (VTE) is a
      worldwide established procedure in hip and knee replacement surgery. Despite
      available anticoagulant prophylaxis, patients who undergo total knee arthroplasty
      (TKA) have a high incidence of venous VTE. In spite of their proven efficacy, the
      currently available anticoagulants have limitations that driven to develop new
      oral agents that directly target specific factors in the coagulation cascade,
      such as direct thrombin inhibitors and direct Factor Xa inhibitors, in an attempt
      to overcome some of the drawbacks with the traditional agents. Apixaban is a
      potent, selective direct inhibitor of the coagulation factor Xa, recently
      approved in Europe for the prevention of venous thromboembolism (VTE) in adult
      patients after total hip replacement (THR) or total knee replacement (TKR)
      surgery. Apixaban has been extensively studied worldwide in about 12,000 patients
      in four clinical studies that have demonstrated the efficacy and safety of
      apixaban respect to enoxaparin for the prevention of thromboembolism after major
      orthopedic surgery. Three of these trials involved 7,337 patients who undergo
      TKR: one phase II trial (APROPOS Study) and two large phase III trials (ADVANCE 1
      and ADVANCE 2 Studies). ADVANCE 1 demonstrated that when compared with enoxaparin
      30 mg twice daily for efficacy, apixaban did not meet the prespecified
      statistical criteria for noninferiority, but its use was associated with lower
      rates of clinically relevant bleeding. ADVANCE 2 showed that apixaban was
      superior to the European standard dose of enoxaparin of 40 mg once daily in term
      of efficacy, with a similar incidence of major bleeding. This review focuses the
      clinical efficacy and tolerability of oral apixaban for the prevention of VTE in
      adult patients following TKR surgery.

PMID- 22466930
TI  - Saddle-splay elasticity and field induced soliton in nematics.
AB  - The symmetry breaking Freedericksz transitions, when a uniformly aligned nematic
      state is replaced by a homogeneously or periodically distorted state, have been
      extensively studied before. Here we analyse the influence of the saddle-splay
      elasticity on the non-linear ground state of a nematic liquid crystal in the
      presence of a magnetic field above the Freedericksz threshold. We identify the
      bifurcation point when the localized soliton-like state is linearly unstable with
      respect to the perturbations of the wavevector in the direction perpendicular to
      the initial plane of the soliton. This instability occurs only if the ratio of
      the saddle-splay elastic constant to the elastic modulus of nematics in the one
      constant approximation is above the critical value K24/K? >=0.707

PMID- 22466931
TI  - Task-specific nitrite and azide ionic liquids for the efficient one-pot synthesis
      of 1,2,3-triazoles from the aniline derivatives.
AB  - An efficient, fast, and straightforward procedure for the synthesis of aromatic
      azides and in situ preparation of 1,2,3-triazoles under mild conditions is
      described. Aniline derivatives have been treated with task-specific [bmim]NO(2)
      and [bmim]N(3) ionic liquids to give the related phenyl azides which, on further
      in situ reaction with 1,3-diketones and ethylacetoacetate, afforded 1,2,3
      triazoles in very good to excellent yields in very short reaction time. This
      procedure, which generates azides followed by azide in situ cycloaddition with
      diketone, has become an attractive option. In this protocol, [bmim]N(3) is used
      instead of the highly toxic reagent NaN(3).

PMID- 22466932
TI  - The biology of chemokines and their receptors.
AB  - This article summarizes the work done by our laboratory and by our collaborators
      on the biological role of chemokines and their receptors. Using both gain-of
      function and loss of function genetic approaches, we have demonstrated that
      chemokines are important for the homeostatic distribution of leukocytes in
      tissues and for their mobilization from the bone marrow. We have also shown that
      chemokines are important players in inflammation and autoimmunity and that they
      contribute to lymphoid organogenesis, angiogenesis, and immune regulation.
      Together, our results and those of the literature suggest an important role for
      chemokines in homeostasis and disease and characterize chemokines as important
      targets for therapeutic intervention.

PMID- 22466934
TI  - True bacteremias caused by coagulase negative Staphylococcus are difficult to
      distinguish from blood culture contaminants.
AB  - Our aim was to test whether or not true bloodstream infections (BSI) caused by
      coagulase negative Staphylococci (CoNS) can be distinguished from blood culture
      contaminants based on simple clinical and laboratory parameters. Patients with
      blood cultures positive for CoNS (n = 471) were categorized into community
      acquired infection (CAI), hospital acquired infection (HAI), infections in
      patients with haematological conditions (HAEI), or culture contaminants (CON)
      based on the judgement of a clinician. The cases were further analyzed according
      to widely accepted criteria for true BSI and whether or not vancomycin treatment
      was initiated. Simple clinical and laboratory parameters, surgical procedures,
      mortality, central venous catheters, and other foreign materials were registered.
      Our study demonstrates that the decision about the significance of positive blood
      culture finding made by the clinician may differ from that indicated by accepted
      criteria for BSI. Simple clinical findings such as heart rate, body temperature,
      or systolic blood pressure may not distinguish a culture contaminant from true
      infections. In addition, the laboratory parameters were surprisingly similar in
      the different patient cohorts. A blood culture positive for CoNS remains a
      clinical challenge; our study demonstrates that judging the significance of the
      finding is difficult.

PMID- 22466933
TI  - Working out mechanisms of controlled/physiologic inflammation in the GI tract.
AB  - The mucosal immune system is distinct from its systemic counterpart by virtue of
      its enormous antigenic exposure (commensal flora, food antigen, pathogens).
      Despite this, the mucosal immune system maintains a response defined as
      controlled or physiologic inflammation. This is regulated by many different
      mechanisms, among which there are physical, cellular and soluble factors. Our
      laboratory has focused on unique Tregs in the gut controlled by, in one instance,
      intestinal epithelial cells that serve as non-professional antigen-presenting
      cells. We believe that intestinal epithelial cells, expressing classical and non
      classical MHC molecules, serve to activate Tregs and thus maintain controlled or
      physiologic inflammation. In this review, we describe regulatory cytokines and T
      cells that are one part of the emphasis of our laboratory.

PMID- 22466936
TI  - Zinc(II) complexes of constrained antiviral macrocycles.
AB  - The configurations of metallocyclams are of interest in relation to protein
      recognition and anti-HIV activity. We have synthesised four novel zinc(II)
      complexes with hexyl-Me(2)-cyclam (HMC; 3,14-dimethyl-2,6,13,17
      tetraazatricyclo(16.4.0.0(7,12))docosane), 1, and naphthyl-hexyl-Me(2)-cyclam
      (NHMC; 2,13-bis(1-naphthylmethyl)-5,16-dimethyl-2,6,13,17
      tetraazatricyclo(16.4.0.0(7,12))docosane), 2, as ligands. X-ray crystallographic
      data for Zn(II)-HMC diacetate, 3 show that zinc is six-coordinate in a distorted
      octahedral environment bound to four equatorial N atoms from the macrocycle and
      two axial acetato O atoms. The 14-membered metallo-macrocycle adopts a trans-III
      (RRSS) configuration with two six-membered rings in chair forms and two five
      membered rings in gauche forms. In the chlorido Zn(II)-HMC complex 5, zinc
      appears to be 5-coordinate with square-pyramidal geometry. Interestingly, the
      chlorido Zn(II)-NHMC complex 6 crystallised in a trans-I configuration containing
      4-coordinate tetrahedral zinc bound to three cyclam ring N atoms, a possible
      model for intermediates formed during the uptake and release of metals by
      cyclams. The ligand 1 and the zinc complex 3 were active towards viral strains
      HIV-1 (III(B)) (IC(50) values of 10.51 +/- 0.23 and 3.50 +/- 0.33 MUM,
      respectively), and HIV-2 (ROD) (IC(50) values of 133.78 +/- 14.10 and >110.67
      MUM, respectively). 2D [(1)H, (13)C] and [(1)H, (15)N] NMR spectroscopic studies
      suggested that the types of configurational isomers present in solution depend on
      the axial ligand.

PMID- 22466935
TI  - Quantitative comparison of errors in 15N transverse relaxation rates measured
      using various CPMG phasing schemes.
AB  - Nitrogen-15 Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation experiment are
      widely used to characterize protein backbone dynamics and chemical exchange
      parameters. Although an accurate value of the transverse relaxation rate, R(2),
      is needed for accurate characterization of dynamics, the uncertainty in the R(2)
      value depends on the experimental settings and the details of the data analysis
      itself. Here, we present an analysis of the impact of CPMG pulse phase
      alternation on the accuracy of the (15)N CPMG R(2). Our simulations show that
      R(2) can be obtained accurately for a relatively wide spectral width, either
      using the conventional phase cycle or using phase alternation when the r.f. pulse
      power is accurately calibrated. However, when the r.f. pulse is miscalibrated,
      the conventional CPMG experiment exhibits more significant uncertainties in R(2)
      caused by the off-resonance effect than does the phase alternation experiment.
      Our experiments show that this effect becomes manifest under the circumstance
      that the systematic error exceeds that arising from experimental noise.
      Furthermore, our results provide the means to estimate practical parameter
      settings that yield accurate values of (15)N transverse relaxation rates in the
      both CPMG experiments.

PMID- 22466938
TI  - Convergence: the tradition and the modern.

PMID- 22466939
TI  - Disease-syndrome combination clinical study of psoriasis: present status,
      advantages, and prospects.
AB  - Psoriasis is an immune-abnormal, chronic, proliferative skin disease determined
      by polygenic inheritance and induced by a number of environmental factors. It
      causes worldwide concern because of its high-prevalence, harmful and incurable
      characteristics. Over the years, Chinese medicine (CM) treatment of psoriasis has
      accumulated a wealth of clinical experience. Disease-syndrome combination, which
      achieves more satisfactory clinical effect, is the basis to highlight the special
      CM advantages in treating psoriasis. In this paper, we review the advantages of
      treating psoriasis with the combination of disease and syndrome, analyze the
      prospects of research on treating psoriasis combining disease with syndrome. We
      also make a point that there are several key points for the clinical research of
      combination of disease and syndrome. It can be expected that carrying out
      clinical research on the combination of disease and syndrome will help improve
      the clinical efficacy of medical treatment of psoriasis, which will be the main
      direction of research in the future.

PMID- 22466940
TI  - Oral herbal medicines for psoriasis: a review of clinical studies.
AB  - Various forms of complementary and alternative medicine are used in psoriasis.
      Among these, herbal medicines are frequently used as systemic and/or topical
      interventions either as a replacement for or in conjunction with conventional
      methods. The benefit of such use is unclear. This review is to provide an up-to
      date review and discussion of the clinical evidence for the main kinds of herbal
      therapies for psoriasis. Searches of the biomedical databases PubMed (including
      MEDLINE), EMBASE and CINAHL were conducted in December 2011 which identified 32
      clinical studies, all published in English. Twenty of these primarily tested
      topical herbal medicines and were thus excluded. The 12 studies that evaluated
      systemic use of herbal medicines were included in the review. Four were case
      series studies and the other 8 were controlled trials. In terms of interventions,
      4 studies tested the systemic use of plant oils combined with marine oils and 8
      studies tested multi-ingredient herbal formulations. The clinical evidence for
      plant and animal derived fatty acids is inconclusive and any benefit appears to
      be small. For the multi-herb formulations, benefits of oral herbal medicines were
      shown in several studies, however, a number of these studies are not controlled
      trials, a diversity of interventions are tested and there are methodological
      issues in the controlled studies. In conclusion, there is promising evidence in a
      number of the studies of multi-herb formulations. However, well-designed,
      adequately powered studies with proper control interventions are needed to
      further determine the benefits of these formulations. In addition, syndrome
      differentiation should be incorporated into trial design to ensure effective
      translation of findings from these studies into Chinese medicine clinical
      practice.

PMID- 22466941
TI  - Application of the dermatology life quality index in clinical trials of biologics
      for psoriasis.
AB  - The significance of patient-reported outcomes (PROs) is increasingly being
      acknowledged and quality of life (QOL) has become an integral element of the
      assessment of overall burden of disease. Psoriasis has been known for its major
      impact on patients' QOL and various generic, dermatology-specific and psoriasis
      specific self-administered psychometric instruments have been used over the years
      to assess the QOL of psoriasis patients. However, the Dermatology Life Quality
      Index (DLQI) is the most widely used QOL measure among these measures in
      psoriasis-related clinical trials. A number of topical and systemic treatments
      have been used in the management of psoriasis and lately biologics have emerged
      as a new and promising treatment modality for difficult-to-treat psoriasis. The
      evidence on the efficacy of these agents has been growing dramatically with QOL
      being used as one of the primary outcome measures in many clinical trials. The
      aim of this paper is to give an overview of the use of the DLQI as an outcome
      measure for assessing the QOL impact of biologics on psoriasis patients.
      Furthermore, the efficacy of five commonly used biologics has been compared in
      terms of their ability to improve the QOL assessed by the DLQI. This review has
      revealed that there is a variation in the efficacy of various biologics in terms
      of QOL improvement with the mean reduction in the DLQI scores being highest for
      ustekinumab 90 mg (mean DLQI score reduction=9.5), followed by infliximab (8.5),
      etanercept 50 mg, twice a week (7.7), adalimumab (6.3), and alefacept (4.0).

PMID- 22466942
TI  - A randomized controlled single-blind clinical trial on 84 outpatients with
      psoriasis vulgaris by auricular therapy combined with optimized Yinxieling
      Formula.
AB  - OBJECTIVE: To explore the therapeutic effect of auricular therapy combined with
      optimized Yinxieling Formula on psoriasis vulgaris. METHODS: A randomized
      controlled single-blind clinical trial on 84 outpatients with psoriasis vulgaris
      was conducted. The patients were randomized to a treatment group (43 cases
      treated by auricular therapy combined with optimized Yinxieling Formula) and a
      control group (41 cases treated by optimized Yinxieling Formula alone) according
      to a random number generated by SPSS 17.0 software. The treatment duration for
      both groups was 8 weeks. The therapeutic effect was comprehensively measured by
      the primary outcome measure [Psoriasis Area and Severity Index (PASI) reduction
      rate] and the secondary outcome measure [PASI, Visual Analogue Scale (VAS),
      Dermatology Life Quality Index (DLQI), Self-rating Depression Scale (SDS), and
      Self-rating Anxiety Scale (SAS)]. The outcomes of both groups were obtained and
      compared before and after the intervention. RESULTS: The PASI reduction rate in
      the treatment group was 74.4% (32/43), which was higher than that in the control
      group (36.6%, 15/41, P<0.01). The PASI scores decreased in both groups after
      treatment and was lower in the treatment group compared with the control group
      P<0.01). With stratified analysis, there were significant differences between the
      PASI scores in the following subgroups: age 18-30, baseline PASI>10 and stable
      stage (P<0.05). DLQI decreased in both groups on some categories after treatment,
      but there were no significant differences between the two groups in SDS, SAS and
      VAS (P >0.05). No obvious adverse reactions were found in either group.
      CONCLUSION: The therapeutic effect of auricular therapy combined with Optimized
      Yinxieling Formula was superior to Optimized Yinxieling Formula alone with no
      obvious adverse reaction.

PMID- 22466943
TI  - Influenza early warning model based on Yunqi theory.
AB  - OBJECTIVE: To establish an early warning model to simulate the outbreak of
      influenza based on weather conditions and Yunqi theory, an ancient calendar
      theory of Chinese medicine (CM). METHODS: Tianjin, a northeastern city in China,
      was chosen as the region of research and applied the influenza-like illness
      attack rate (ILI)% as the baseline and warning line to determine the severity of
      influenza epidemic. Then, an influenza early warning model was constructed based
      on the theory of rough set and support vector machines (RS-SVM), and the
      relationship between influenza and meteorology was explored through analyzing the
      monitoring data. RESULTS: The predictive performance of the model was good, which
      had achieved 81.8% accuracy when grouping the obtained data into three levels
      that represent no danger, danger of a light epidemic, and danger of a severe
      epidemic. The test results showed that if the host qi and guest qi were not
      balanced, this kind of situation was more likely to cause influenza outbreaks.
      CONCLUSIONS: The outbreak of influenza closely relates to temperature, humidity,
      visibility, and wind speed and is consistent with some part of CM doctrine. The
      result also indicates that there is some reasonable evidence in the Yunqi theory.

PMID- 22466944
TI  - Total saponin from root of Actinidia valvata Dunn prevents the metastasis of
      human hepatocellular carcinoma cells.
AB  - OBJECTIVE: To extract the active component from the root of Actinidia valvata
      Dunn and to investigate the effects on hepatocellular carcinoma (HCC) cells in
      vitro. METHODS: Total saponin was extracted from the root of A. valvata (TSAVD).
      HCC cells, such as BEL-7402, HepG2, PLC, SMMC-7721, MHCC-97-H, and MHCC-97-L,
      were treated with TSAVD in 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenytetrazolium
      bromide (MTT) assay. BEL-7402 and MHCC-97-H cells were also treated respectively
      with TSAVD at different concentrations for 24 h in wound healing and adhesion
      assays, and the effects of TSAVD on BEL-7402 and MHCC-97-H cells mobility and
      adhesion abilities were observed. Meanwhile, the effects of TSAVD on invasion and
      migration of BEL-7402 and MHCC-97-H cells were also investigated by transwell
      chamber in invasion and migration assays. RESULTS: TSAVD at 1.5 mg/mL inhibited
      BEL-7402 cell proliferation with inhibition ratios (IRs) of 61.08%, 74.12%,
      84.55% at 24, 48, and 72 h, respectively. Meanwhile, TSAVD inhibited MHCC-97-H
      proliferation in a concentration-dependent manner from 1.5 to 0.5 mg/mL, with the
      IR of 36% at 1.5 mg/mL at 24 h. For SMMC-7721, PLC, and HepG2, the IR was lower
      than 30% at 1.5 mg/mL at 24 h. In the wound healing assay, mobility abilities of
      BEL-7402 and MHCC-97-H cells in TSAVD treated groups were significantly weaker
      than those of the control group. After pretreatment for 24 h with TSAVD, adhesion
      abilities were reduced in both MHCC-97-H and BEL-7402 cells, with IRs of 48.50%+/
      4.86% and 49.85%+/-5.25% at 200 MUg/mL. The IRs of MHCC-97-H and BEL-7402 cells
      in the migration assay were 49.13%+/-2.91% and 79.37%+/-0.09% at 200 MUg/mL. In
      the invasion assay, IRs were 69.78%+/-4.88% and 82.48%+/-0.25% at 200 MUg/mL.
      CONCLUSIONS: Of all HCC cells, the highest inhibition by TSAVD was seen for BEL
      7402 proliferation. TSAVD could restrain adhesion, invasion, mobility, and
      migration abilities of BEL-7402 and MHCC-97-H cells in vitro.

PMID- 22466945
TI  - Carboxymethylpachymaran enhances immunologic function of dendritic cells cultured
      in two kinds of hepatoma carcinoma cell line's supernatant via nuclear factor
      kappa B/Rel pathway.
AB  - OBJECTIVE: To study the immunologic function of dendritic cells (DCs) cultured in
      two kinds of hepatoma cell line's supernatant and the enhancing effects of
      carboxymethylpachymaran (CMP) on DCs. METHODS: DCs were harvested after
      stimulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      interleukin (IL)-4 from umbilical cord blood using density-gradient
      centrifugation method. Cultured supernatant of two hepatoma cell lines (HepG2 and
      HepG2.2.15) were collected for condition medium (CM) according to a volume ratio
      of supernatant to incomplete RPMI-1640 medium, which was 3:1. CMP was dissolved
      in incomplete RPMI-1640 medium. Experimental groups were divided according to the
      culture medium, either CM or with CMP in it. DCs subsets CD83, CD86, CD1a, and d
      related human leukocyte antigens (HLA-DR) were analyzed by flow cytometry. The
      proliferation ability of allogeneic T cells in mixed lymphocyte reaction (MLR)
      stimulated by DCs was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) analysis. IL-12p70, interferon-gamma (IFN
      gamma), and nuclear factor kappaB (NF-kappaB) were detected by enzyme-linked
      immunosorbent assay analysis. RESULTS: The proliferation of lymphocytes and
      secreting level of IL-12 and expression of phenotype of DCs cultured in two kinds
      of CM were lower than those of normal group (P <0.01). Compared with the normal
      group, groups treated with CMP showed a higher expression level of DCs subsets,
      lymphocyte reproductive activity, as well as IL-12 and IFN-gamma secretion
      levels. Groups treated with CMP also demonstrated higher levels of DCs phenotype
      expression and IL-12 and IFN-gamma secretion in supernatant of MLR and higher
      lymphocyte reproductive activity compared with CM group (P <0.05). Compared with
      the normal group, the expression level of NF-kappaB in DCs nuclear was higher in
      CMP groups but lower in two CM groups (P <0.05). After CMP was added, the NF
      kappaB expression levels of two CM groups were increased compared with levels
      before CMP was added (P <0.05). However, there was no significant difference
      between the two CM groups (P >0.05). CONCLUSIONS: Two kinds of hepatoma cell
      line's supernatant can inhibit the immunologic function of DCs. This suppressive
      effect may be related to the inhibition of NF-kappaB/Rel pathway. CMP may up
      regulate the DCs function by activating the NF-kappaB/Rel pathway.

PMID- 22466946
TI  - Oxysophoridine suppresses the growth of hepatocellular carcinoma in mice: in vivo
      and cDNA microarray studies.
AB  - OBJECTIVE: To observe the in vivo effects of oxysophoridine on hepatocellular
      carcinoma in mice and to study the related mechanisms. METHODS: C57BL mice were
      inoculated with mouse hepatoma H22 cells subcutaneously, then divided into 5
      groups (14 per group), and treated with oxysophoridine (50, 100, or 150 mg/kg) or
      cisplatin (4 mg/kg) for 10 days. Inhibitory rate of tumor, body weight gain, and
      influence indices on internal organs (liver, spleen and thymus) were evaluated.
      The differentially expressed genes between the oxysophoridine-treated group, and
      the control group were analyzed using cDNA microarray and quantitative real-time
      PCR (qRT-PCR) experiments. RESULTS: Compared with the tumor weight of the control
      group (2.75+/-0.66 g), oxysophoridine significantly suppressed hepatocellular
      carcinoma growth in mice (P <0.01), with 0.82+/-0.36 g, 0.57+/-0.22 g, and 1.22+/
      0.67 g for the tumor weight in the low, moderate, and high dose treatment group,
      respectively. The moderate dose led to the highest inhibitory rate, 79.3%.
      Observation of body weight gain and influence on three organs showed that
      compared with cisplatin, oxysophoridine produced fewer side effects in vivo. cDNA
      microarray and qRT-PCR showed that the most significant differentially expressed
      genes in the tumor samples of oxysophoridine-treated mice were mostly involved in
      regulating apoptosis, with the Tnfrsf11b (osteoprotegerin) gene being the most
      significantly affected. CONCLUSION: Oxysophoridine was a promising compound for
      developing drugs against hepatocellular carcinoma, and its anti-hepatoma effect
      was probably related to osteoprotegerin activation.

PMID- 22466947
TI  - Clinical effect of sphenopalatine ganglion needling in treating primary
      trigeminal neuralgia of Liver-yang upsurge syndrome type.
AB  - OBJECTIVE: To observe the efficacy and safety of sphenopalatine ganglion needling
      in treating patients with primary trigeminal neuralgia (PTN) of Liver (Gan)-yang
      upsurge syndrome (LYUS) type. METHODS: Sixty-five PTN patients of LYUS type were
      assigned by a random number table to two groups and treated by deep-needling (33
      patients, DN group) and superficial-needling (32 patients, SN group),
      respectively. The main-acupoint used for both groups was Xiaguan (ST7) of
      affected side, on which needle was deeply inserted to reach spheno-palatine
      ganglion in the DN group, but was inserted conventionally in the SN group; the
      auxiliary acupoints used were the local points Cuanzhu (BL2), Sibai (ST2),
      Chengjiang (CV24) of affected side, as well as the remote points, bilateral Hegu
      (LI4) and Taichong (LR3). The needling was implemented every other day, with
      electric stimulation applied to all the punctured acupoints for 30 min, 10 days
      treatment as one therapeutic course. Each patient received 2 courses of needling
      with 1 week interval in between. The clinical efficacy, pain control and adverse
      reaction were evaluated and compared after the treatment. RESULTS: Rank-sum test
      showed that the efficacy in the DN group was significantly better than that in
      the SN group (Z =2.30, P=0.021); the pain was alleviated in both groups in
      frequency, intensity and sustained time (evaluated by visual analogue scale)
      significantly (P<0.01), but deep needling showed a superiority over superficial
      needling in reducing the frequency and intensity of episode (Z=9.55, Z=5.50, both
      P=0.00). No adverse reaction occurred during the treatment course of both groups.
      CONCLUSION: Spheno-palatine ganglion needling is highly effective, safe and
      reliable for the treatment of PTN.

PMID- 22466948
TI  - Chinese medicine in the treatment of Behcet's disease's uveitis: a case report.

PMID- 22466949
TI  - Efficacy of externally applied Chinese herbal drugs in treating psoriasis: a
      systematic review.
AB  - OBJECTIVE: To assess the efficacy and safety of external application of Chinese
      herbal drugs (ex-CHD) in the treatment of psoriasis. METHODS: Literature
      regarding randomized clinical trials (RCTs) of psoriasis treatments with ex-CHD,
      either alone or combined with Western medicine (WM) or physiotherapy, controlled
      by untreated, placebo or WM treatment were found in electronic databases,
      including PubMed/MEDLINE, EMBASE, Cochrane Library, Cochrane Central Register of
      Controlled Trials, China Biology Medicine Disc (CBM), Chinese National Knowledge
      Infrastructure (CNKI), Wanfang database and VIP database from their inception
      through July 2011. Study selection, data extraction, quality assessment, and data
      analyses were conducted according to the Cochrane standards. RESULTS: A total of
      10 randomized trials (involving 1,435 patients) were included. Because both test
      and control drugs used in the RCTs were different from each other, the effects
      can only be described singly and calculated. Regarding the total effective rate
      for the treatment of psoriasis, ex-CHD in combination with ultraviolet radiation
      b (UVB) or narrow band ultraviolet radiation b (NB-UVB), which was reported in 6
      trials, was superior to UVB alone. One study reported that ex-CHD and externally
      applied WM had equivalent effects. In another study, ex-CHD showed better results
      than placebo. However, another two comparisons of ex-CHD and WM (all in combining
      with oral WM) showed uncertain outcomes. Nine trials reported adverse reactions.
      Of these, 7 RCTs included statistical analysis. The results showed that the side
      effects that occurred in ex-CHD combined with UVB were less severe than those
      caused by UVB alone, but the incidence was roughly the same as WM. CONCLUSION:
      The evidence supporting the efficacy of ex-CHD with respect to treating psoriasis
      is quite limited and must be strengthened by high-quality studies.

PMID- 22466950
TI  - Heated moxibustion and bloodletting in Tibetan medical literature of Dunhuang
      Heritage.
AB  - The paper introduces the heated moxibustion and bloodletting in Tibetan medical
      literature of Dunhuang Heritage. It proves that the external therapies in Tibetan
      medicine such as heated moxibustion and bloodletting are of very high level since
      the 8th century, which inspires current clinical practice. It also shows that the
      extensive exchange between Tibetan medicine and various kinds of medicine such as
      Chinese medicine promoted the development of Tibetan medicine.

PMID- 22466951
TI  - Research progress on mechanism of action of Radix Astragalus in the treatment of
      heart failure.
AB  - This paper reviewed the retrieved literature published in the last 10 years,
      regarding the mechanism of Radix Astragalus in treating heart failure, in aspects
      of myocardial contraction improvement, cardiac muscle cell protection, neuro
      endocrinal system regulation, relative cytokine regulation, and left ventricular
      remodeling inhibition, etc.

PMID- 22466952
TI  - Transcriptional and preliminary functional analysis of the six genes located in
      divergence of phoR/phoP in Streptomyces lividans.
AB  - Streptomyces lividans senses and adjusts to a situation of Pi limitation via the
      expression of genes of the pho regulon controlled by the two-component system
      PhoR/PhoP. Interestingly, an in silico analysis of the proteins encoded by the
      six genes located in divergence of phoR/phoP revealed that the latter bear
      features often found in metalloproteins involved in the sensing/resistance to
      oxidative stress. We determined whether genes of this region were belonging to
      the pho regulon and whether the encoded proteins do play a role in the resistance
      to oxidative stress. For this purpose, a transcriptional analysis of these genes
      was carried out on the carbon and nitrogen rich medium R2YE and on a minimal
      medium (MM). On R2YE, the expression of the genes phoU to sco4225 was much higher
      than on MM and constant throughout growth. On this medium, the expression of phoU
      was totally PhoP-dependent whereas the expression of sco4227 and sco4226 was
      partially PhoP-dependent, taking place from the phoU promoter region. In
      contrast, on MM, the expression of sco4227 and sco4226 was PhoP-independent
      whereas that of phoU remained PhoP-dependent and showed, as phoR/phoP, a peak of
      expression at 48 h. sco4225, sco4224, and sco4223 were transcribed from their own
      promoter independently of PhoP in both media. The mutants of five out of six
      genes of the region (Deltasco4226 mutant could not be obtained) grew poorly in
      the presence of exogenous oxidants, suggesting a role of the encoded proteins in
      the resistance to oxidative stress, especially on the rich medium R2YE.

PMID- 22466953
TI  - Identification of nicotine biotransformation intermediates by Agrobacterium
      tumefaciens strain S33 suggests a novel nicotine degradation pathway.
AB  - Nicotine, a major alkaloid in tobacco plants and the main toxic chemical in
      tobacco wastes, can be transformed by bacteria into hydroxylated-pyridine
      intermediates, which are important precursors for the chemical synthesis of
      valuable drugs and insecticides. Such biotransformation could be a useful
      approach to utilize tobacco and its wastes. In this study, we explored nicotine
      degradation by a recently isolated Agrobacterium tumefaciens S33 by identifying
      the intermediates during its growth on nicotine and during transformation of
      nicotine with its resting cells. Five hydroxylated-pyridine intermediates were
      detected through multiple approaches, including GC-HR-MS, HPLC, and ESI-Q-TOF MS
      analyses. Surprisingly, these identified intermediates suggest that strain S33
      employs a novel pathway that is different from the two characterized pathways
      described in Arthrobacter and Pseudomonas. Based on these findings, we propose
      that strain S33 is able to transform nicotine to 6-hydroxy-pseudooxynicotine
      first via the pyridine pathway through 6-hydroxy-L-nicotine and 6-hydroxy-N
      methylmyosmine, and then, it turns to the pyrrolidine pathway with the formation
      of 6-hydroxy-3-succinoylpyridine and 2,5-dihydroxypyridine. The activities of the
      key enzymes, nicotine dehydrogenase, 6-hydroxy-L-nicotine oxidase, and 6-hydroxy
      3-succinoylpyridine hydroxylase, were demonstrated in the cell extract of strain
      S33 and by partially enriched enzymes. Moreover, the cell extract could transform
      6-hydroxy-pseudooxynicotine into 6-hydroxy-3-succinoylpyridine by coupling with 6
      hydroxy-L-nicotine oxidation reaction by 6-hydroxy-L-nicotine oxidase. These
      results indicated that strain S33 can transform nicotine into renewable
      hydroxylated-pyridine intermediates by the special pathway, in which at least
      three intermediates, 6-hydroxy-L-nicotine, 6-hydroxy-3-succinoylpyridine, and 2,5
      dihydroxypyridine, have potential to be further chemically modified into useful
      compounds.

PMID- 22466954
TI  - Engineering global transcription factor cyclic AMP receptor protein of
      Escherichia coli for improved 1-butanol tolerance.
AB  - One major challenge in biofuel production, including biobutanol production, is
      the low tolerance of the microbial host towards increasing biofuel concentration
      during fermentation. Here, we have demonstrated that Escherichia coli 1-butanol
      tolerance can be greatly enhanced through random mutagenesis of global
      transcription factor cyclic AMP receptor protein (CRP). Four mutants (MT1-MT4)
      with elevated 1-butanol tolerance were isolated from error-prone PCR libraries
      through an enrichment screening. A DNA shuffling library was then constructed
      using MT1-MT4 as templates and one mutant (MT5) that exhibited the best tolerance
      ability among all variants was selected. In the presence of 0.8 % (v/v, 6.5 g/l)
      1-butanol, the growth rate of MT5 was found to be 0.28 h(-1) while that of wild
      type was 0.20 h(-1). When 1-butanol concentration increased to 1.2 % (9.7 g/l),
      the growth rate of MT5 (0.18 h(-1)) became twice that of the wild type (0.09 h(
      1)). Microbial adhesion to hydrocarbon test showed that cell surface of MT5 was
      less hydrophobic and its cell length became significantly longer in the presence
      of 1-butanol, as observed by scanning electron microscopy. Quantitative real-time
      reverse transcription PCR analysis revealed that several CRP regulated, 1-butanol
      stress response related genes (rpoH, ompF, sodA, manX, male, and marA)
      demonstrated differential expression in MT5 in the presence or absence of 1
      butanol. In conclusion, direct manipulation of the transcript profile through
      engineering global transcription factor CRP can provide a useful tool in strain
      engineering.

PMID- 22466955
TI  - Determining novel molecular markers in the Chinese caterpillar fungus
      Ophiocordyceps sinensis by screening a shotgun genomic library.
AB  - The Chinese caterpillar fungus Ophiocordyceps sinensis, endemic to alpine regions
      on the Tibetan Plateau, is one of the most valuable medicinal fungi in the world.
      Genetic differentiation within this fungus was observed; however, due to lack of
      highly efficient molecular markers, the overall genetic structure of this fungus
      has not been clarified. In this study, a shotgun genomic library of O. sinensis
      was constructed, and >181,848 nt were analyzed from >250 random clones. Primers
      from 33 sequenced fragments were then designed to amplify O. sinensis samples
      collected from widely separated regions on the Tibetan Plateau. Ten of the 33
      fragments had no amplification or poor sequencing quality from all or certain
      samples. Sequence variations of the remaining 23 fragments among different
      samples were investigated in detail. Three fragments (OSRC14, OSRC19, and OSRC32)
      were the most variable with 7-43 single-nucleotide polymorphism (SNP) sites,
      representing the SNP frequency of 1.2-6.7 % per nucleotide site. These three
      fragments have the potential to be useful molecular markers for studying the
      population genetics of O. sinensis. These results also showed that constructing
      and screening a shotgun genomic library was an efficient approach to identify
      novel molecular markers from non-model organisms.

PMID- 22466956
TI  - Hemin/G-quadruplex simultaneously acts as NADH oxidase and HRP-mimicking DNAzyme
      for simple, sensitive pseudobienzyme electrochemical detection of thrombin.
AB  - For the first time, hemin/G-quadruplex was employed to simultaneously serve as
      NADH oxidase and an HRP-mimicking DNAzyme for constructing a simple and sensitive
      pseudobienzyme-amplifying electrochemical aptasensor for thrombin detection.

PMID- 22466957
TI  - Genetic diversity in European Pisum germplasm collections.
AB  - The distinctness of, and overlap between, pea genotypes held in several Pisum
      germplasm collections has been used to determine their relatedness and to test
      previous ideas about the genetic diversity of Pisum. Our characterisation of
      genetic diversity among 4,538 Pisum accessions held in 7 European Genebanks has
      identified sources of novel genetic variation, and both reinforces and refines
      previous interpretations of the overall structure of genetic diversity in Pisum.
      Molecular marker analysis was based upon the presence/absence of polymorphism of
      retrotransposon insertions scored by a high-throughput microarray and SSAP
      approaches. We conclude that the diversity of Pisum constitutes a broad
      continuum, with graded differentiation into sub-populations which display various
      degrees of distinctness. The most distinct genetic groups correspond to the named
      taxa while the cultivars and landraces of Pisum sativum can be divided into two
      broad types, one of which is strongly enriched for modern cultivars. The addition
      of germplasm sets from six European Genebanks, chosen to represent high
      diversity, to a single collection previously studied with these markers resulted
      in modest additions to the overall diversity observed, suggesting that the great
      majority of the total genetic diversity collected for the Pisum genus has now
      been described. Two interesting sources of novel genetic variation have been
      identified. Finally, we have proposed reference sets of core accessions with a
      range of sample sizes to represent Pisum diversity for the future study and
      exploitation by researchers and breeders.

PMID- 22466958
TI  - The effects of curcumin post-treatment against myocardial ischemia and
      reperfusion by activation of the JAK2/STAT3 signaling pathway.
AB  - In this study, we evaluated the effect of curcumin (Cur) post-treatment on
      isolated perfused rat hearts that had been subjected to a protocol of ischemia
      and reperfusion injury. We also examined whether the Janus kinase 2 and signal
      transducer and activator 3 of transcription (JAK2/STAT3) signaling pathway plays
      a role in the cardioprotective effects of Cur post-treatment. Isolated perfused
      rat hearts were subjected to 60 min of ischemia, followed by 60 min of
      reperfusion. The hearts were exposed to 1-MUM Cur during the first 10 min of
      reperfusion in the absence or presence of the JAK kinase-specific inhibitor AG490
      (AG, 1 MUM). The Cur treatment conferred a cardioprotective effect, and the
      treated hearts demonstrated an improved post-ischemic cardiac functional
      recovery, a decreased myocardial infarct size and decreased lactate dehydrogenase
      release in the coronary flow, a reduced number of apoptotic cardiomyocytes, up
      regulation of the anti-apoptotic protein Bcl2 and down-regulation of the pro
      apoptotic protein Caspase3. AG blocked the Cur-mediated cardioprotection by
      inhibiting the JAK2/STAT3 signaling pathway, as reflected by the abrogation of
      the Cur-induced up-regulation of Bcl2 and down-regulation of Caspase3. The
      results suggest that Cur post-treatment can attenuate IR injury through the
      activation of the JAK2/STAT3 signaling pathway, which transmits a survival signal
      to the myocardium.

PMID- 22466960
TI  - Activation of ERK-p53 and ERK-mediated phosphorylation of Bcl-2 are involved in
      autophagic cell death induced by the c-Met inhibitor SU11274 in human lung cancer
      A549 cells.
AB  - SU11274, a small molecule inhibitor of c-Met, was reported to induce apoptosis in
      human non-small-cell lung cancer (NSCLC) cells. However, SU11274-mediated
      autophagy in NSCLC cells has rarely been reported. The aim of this study was to
      elucidate the molecular mechanisms mediating SU11274-induced autophagy in NSCLC
      A549 cells. Here we reported that SU11274-induced autophagy was accompanied with
      an increase in the conversion of LC3-I to LC3-II and up-regulation of Beclin-1
      expression. Subsequently, we also found that small interfering RNA against c-Met
      induced A549 cell autophagy while promotion of c-Met by hepatocyte growth factor
      (HGF) suppressed A549 cell autophagy. Inhibition of autophagy by 3-methyladenine
      (3-MA) suppressed SU11274-induced cell death, suggesting that SU11274-induced
      autophagy caused cell death. Further study showed that ERK and p53 were activated
      after SU11274 treatment. Interruption of ERK and p53 activities decreased SU11274
      induced autophagy, and blocking of ERK by the specific inhibitor PD98059
      suppressed SU11274-induced p53 activation. Moreover, ERK activation upregulated
      Beclin-1 expression through induction of Bcl-2 phosphorylation, but p53 did not
      induce Bcl-2 phosphorylation. In conclusion, inhibition of c-Met induced
      autophagic cell death, which was associated with ERK-p53 activation and ERK
      mediated Bcl-2 phosphorylation in A549 cells.

PMID- 22466959
TI  - Contribution of voltage-dependent K+ and Ca2+ channels to coronary pressure-flow
      autoregulation.
AB  - The mechanisms responsible for coronary pressure-flow autoregulation, a critical
      physiologic phenomenon that maintains coronary blood flow relatively constant in
      the presence of changes in perfusion pressure, remain poorly understood. This
      investigation tested the hypothesis that voltage-sensitive K(+) (K(V)) and Ca(2+)
      (Ca(V)1.2) channels play a critical role in coronary pressure-flow autoregulation
      in vivo. Experiments were performed in open-chest, anesthetized Ossabaw swine
      during step changes in coronary perfusion pressure (CPP) from 40 to 140 mmHg
      before and during inhibition of K(V) channels with 4-aminopyridine (4AP, 0.3 mM,
      ic) or Ca(V)1.2 channels with diltiazem (10 MUg/min, ic). 4AP significantly
      decreased vasodilatory responses to H(2)O(2) (0.3-10 MUM, ic) and coronary flow
      at CPPs = 60-140 mmHg. This decrease in coronary flow was associated with
      diminished ventricular contractile function (dP/dT) and myocardial oxygen
      consumption. However, the overall sensitivity to changes in CPP from 60 to 100
      mmHg (i.e. autoregulatory gain; Gc) was unaltered by 4-AP administration (Gc =
      0.46 +/- 0.11 control vs. 0.46 +/- 0.06 4-AP). In contrast, inhibition of
      Ca(V)1.2 channels progressively increased coronary blood flow at CPPs > 80 mmHg
      and substantially diminished coronary Gc to -0.20 +/- 0.11 (P < 0.01), with no
      effect on contractile function or oxygen consumption. Taken together, these
      findings demonstrate that (1) K(V) channels tonically contribute to the control
      of microvascular resistance over a wide range of CPPs, but do not contribute to
      coronary responses to changes in pressure; (2) progressive activation of Ca(V)1.2
      channels with increases in CPP represents a critical mechanism of coronary
      pressure-flow autoregulation.

PMID- 22466961
TI  - Synergism between interleukin (IL)-17 and Toll-like receptor 2 and 4 signals to
      induce IL-8 expression in cystic fibrosis airway epithelial cells.
AB  - Cystic fibrosis (CF) is the most common lethal inherited disorder and is caused
      by mutations in the gene encoding the CF transmembrane regulator (CFTR). The CF
      lung expresses a profound proinflammatory phenotype that appears to be related to
      a constitutive hypersecretion of interleukin (IL)-8 from airway epithelial cells
      in response to microbial infection. Since overproduction of IL-8 in CF
      contributes to massive bronchial infiltrates of neutrophils, identification of
      the pathways underlying IL-8 induction could provide novel drug targets for
      treatment of neutrophil-dominated inflammatory diseases such as CF. Here, we show
      that IL-17A synergistically increases IL-8 production induced by a toll-like
      receptor (TLR) 2 agonist, peptidoglycan (PGN), or TLR4 agonist,
      lipopolysaccharide (LPS), in a human CF bronchial epithelial cell line (CFBE41o
      ). A strong synergism was also observed in primary human CF bronchial epithelial
      cells, but not in human non-CF cell lines and primary cells. Notably, despite the
      induction of nuclear factor-kappaB and MAP kinases during TLR2 or TLR4 activation
      in CFBE41o-, IL-17A-dependent synergism appears to be the result of enhanced PGN-
      or LPS-induced phosphorylation of p38. Taken together, these studies provide
      evidence that IL-17A is a critical factor in increasing IL-8 expression in
      bacteria-infected CF airways via a pathway that regulates p38 phosphorylation.

PMID- 22466962
TI  - Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical
      allodynia in rats.
AB  - Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes
      acute and chronic neuropathies in patients. Amitriptyline has widely been used in
      patients with painful neuropathy. In this study, we investigated the effect of
      amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated
      administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the
      oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed
      the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in
      rat spinal cord. These results suggest that amitriptyline is useful for the
      treatment of oxaliplatin-induced neuropathy clinically.

PMID- 22466963
TI  - Electrophysiological effects of the class Ic antiarrhythmic drug pilsicainide on
      the guinea-pig pulmonary vein myocardium.
AB  - The pulmonary vein is known as an important source of ectopic beats, initiating
      frequent paroxysms of atrial fibrillation. We compared effects of the class Ic
      antiarrhythmic drug pilsicainide on the electrophysiological parameters in the
      isolated pulmonary vein preparation from guinea pigs with those in the left
      atrium. Three pairs of bipolar electrodes were attached to the left atrium,
      pulmonary vein, and junctional region of the left atrium and pulmonary vein to
      measure intra-atrial and intra-pulmonary vein conduction velocity and effective
      refractory period. Pilsicainide (10 uM) decreased the conduction velocity in the
      pulmonary vein as well as the left atrium, whose effect on the pulmonary vein was
      relatively greater than that on the left atrium. The drug prolonged the effective
      refractory period in the pulmonary vein as well as the left atrium, and the
      effect of the drug on the pulmonary vein was less than that on the left atrium.
      The currently observed electrophysiological property of pilsicainide suggests
      that its effects on reentry within the pulmonary vein are estimated to be weaker
      than within the left atrium, which may be one of the key considerations for
      understanding its antiarrhythmic mechanisms in the atrium and pulmonary vein.

PMID- 22466964
TI  - NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway.
AB  - The AAA+ ATPase p97 and its UBA-UBX cofactors are thought to extract
      ubiquitinated proteins from membranes or protein complexes as a prelude to their
      degradation. However, for many cofactors ubiquitinated targets have not yet been
      identified, leaving their biological function unclear. Previous analysis has
      linked the p97 pathway to cullin-RING ubiquitin ligases (CRLs); here we
      demonstrate that the human p97 cofactor UBXD7 mediates the p97-CRL interaction
      through its conserved ubiquitin-interacting motif (UIM). UBXD7 and its yeast
      ortholog, Ubx5, associate only with the active, NEDD8- or Rub1-modified form of
      cullins. Disruption of the Ubx5 UIM results in a loss of CRL binding and
      consequently impedes degradation of a Cul3 substrate. These results uncover an
      unexpected and conserved role for NEDD8 in linking CRL ubiquitin ligase function
      to the p97 pathway.

PMID- 22466965
TI  - p53-mediated heterochromatin reorganization regulates its cell fate decisions.
AB  - p53 is a major sensor of cellular stresses, and its activation influences cell
      fate decisions. We identified SUV39H1, a histone code 'writer' responsible for
      the histone H3 Lys9 trimethylation (H3K9me3) mark for 'closed' chromatin
      conformation, as a target of p53 repression. SUV39H1 downregulation was mediated
      transcriptionally by p21 and post-translationally by MDM2. The H3K9me3 repression
      mark was found to be associated with promoters of representative p53 target genes
      and was decreased upon p53 activation. Overexpression of SUV39H1 maintained
      higher levels of the H3K9me3 mark on these promoters and was associated with
      decreased p53 promoter occupancy and decreased transcriptional induction in
      response to p53. Conversely, SUV39H1 pre-silencing decreased H3K9me3 levels on
      these promoters and enhanced the p53 apoptotic response. These findings uncover a
      new layer of p53-mediated chromatin regulation through modulation of histone
      methylation at p53 target promoters.

PMID- 22466966
TI  - Discovery of an archetypal protein transport system in bacterial outer membranes.
AB  - Bacteria have mechanisms to export proteins for diverse purposes, including
      colonization of hosts and pathogenesis. A small number of archetypal bacterial
      secretion machines have been found in several groups of bacteria and mediate a
      fundamentally distinct secretion process. Perhaps erroneously, proteins called
      'autotransporters' have long been thought to be one of these protein secretion
      systems. Mounting evidence suggests that autotransporters might be substrates to
      be secreted, not an autonomous transporter system. We have discovered a new
      translocation and assembly module (TAM) that promotes efficient secretion of
      autotransporters in proteobacteria. Functional analysis of the TAM in Citrobacter
      rodentium, Salmonella enterica and Escherichia coli showed that it consists of an
      Omp85-family protein, TamA, in the outer membrane and TamB in the inner membrane
      of diverse bacterial species. The discovery of the TAM provides a new target for
      the development of therapies to inhibit colonization by bacterial pathogens.

PMID- 22466968
TI  - A Streptococcus pneumoniae infection model in larvae of the wax moth Galleria
      mellonella.
AB  - The bacterium Streptococcus pneumoniae is a leading human opportunistic pathogen.
      The limitations of the current vaccine have led to increased recognition of the
      need to understand bacterial behaviour and competitive dynamics using in vivo
      models of infection. Here, we investigate the potential application of the larvae
      of the wax moth Galleria mellonella as an informative infection model. Larvae
      were challenged with a range of doses of S. pneumoniae isolates differing in
      known virulence factors to determine the LD(50) values. Infection dynamics were
      determined by obtaining bacterial counts from larvae over a time course.
      Differences in virulence between serotypes could be distinguished in this host.
      Infection with strains differing in known virulence factors demonstrated
      predicted differences in virulence. Acapsulate and pneumolysin-negative strains
      were less virulent than their respective wild types. A large reduction in
      virulence was seen in strains lacking cell wall D-alanylation. The mortality of
      G. mellonella larvae is attributable to bacterial growth within larvae, while
      surviving larvae are able to clear infections by reducing bacterial numbers.
      These data demonstrate that G. mellonella larvae represent an in vivo infection
      model with applications for investigating aspects of bacterial-host interactions
      such as the role of antimicrobial peptide activity and resistance.

PMID- 22466969
TI  - Healthcare-associated infection prevention in pediatric intensive care units: a
      review.
AB  - The objective of this review was to summarize the current knowledge base on the
      prevention of nosocomial infections in pediatric intensive care units (PICUs).
      Healthcare-associated infections (HAIs) are a crucial problem in PICUs because of
      their impact on patient outcome, length of hospital stay, and costs. Studies
      published between 1998 and 2011 were identified using the MEDLINE and Cochrane
      databases. Randomized, cohort, case-control studies, and meta-analyses concerning
      global strategies of prevention, general organization of the wards, general
      recommendations on antibiotic management, and measures for the prevention of
      ventilator-associated pneumonia (VAP), bloodstream infections (BSIs), urinary
      tract infections (UTIs), and surgical site infections (SSIs) were incorporated.
      Limits of age from 1 month to 18 years were used. When recommendations could not
      be supported by the pediatric literature, adult studies were also reviewed. This
      review excludes the neonate population. Specific pediatric data are often lacking
      so as to establish specific evidence-based pediatric recommendations. This review
      underlines the absolute necessity of pediatric studies and to harmonize the
      definitions of HAIs.

PMID- 22466970
TI  - Role of chloride ion in hydroxyl radical production in photosystem II under heat
      stress: electron paramagnetic resonance spin-trapping study.
AB  - Hydroxyl radical (HO*) production in photosystem II (PSII) was studied by
      electron paramagnetic resonance (EPR) spin-trapping technique. It is demonstrated
      here that the exposure of PSII membranes to heat stress (40  degrees C) results
      in HO* formation, as monitored by the formation of EMPO-OH adduct EPR signal. The
      presence of different exogenous halides significantly suppressed the EMPO-OH
      adduct EPR signal in PSII membranes under heat stress. The addition of exogenous
      acetate and blocker of chloride channel suppressed the EMPO-OH adduct EPR signal,
      whereas the blocker of calcium channel did not affect the EMPO-OH adduct EPR
      signal. Heat-induced hydrogen peroxide (H2O2) production was studied by amplex
      red fluorescent assay. The presence of exogenous halides, acetate and chloride
      blocker showed the suppression of H2O2 production in PSII membranes under heat
      stress. Based on our results, it is proposed that the formation of HO* under heat
      stress is linked to uncontrolled accessibility of water to the water-splitting
      manganese complex caused by the release of chloride ion on the electron donor
      side of PSII. Uncontrolled water accessibility to the water-splitting manganese
      complex causes the formation of H2O2 due to improper water oxidation, which leads
      to the formation of HO* via the Fenton reaction under heat stress.

PMID- 22466971
TI  - Determinants of effective cooling during endovascular hypothermia.
AB  - BACKGROUND: Therapeutic hypothermia is a promising neuroprotective therapy with
      multiple mechanisms of action. We demonstrated the feasibility of thrombolysis
      combined with endovascular hypothermia, but not all patients achieved effective
      cooling. We sought to identify the factors that determined effective cooling.
      METHODS: In 26 patients who underwent endovascular hypothermia, we computed four
      measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC)
      34 ratio; AUC-34; and AUC-35. By multivariate regression, we examined the effects
      of age, weight, starting temperature, body mass index, body surface area (BSA),
      gender, shivering, and total meperidine dose on the four outcome measures.
      RESULTS: In univariate analyses, all four outcome measures were significantly
      influenced by BSA (p < 0.01 in all univariate analyses). Time to reach target
      temperature was quicker in older patients (p < 0.01). Shivering and meperidine
      dose were highly intercorrelated (r = 0.6, p < 0.01) and both marginally
      influenced all four outcome measures. In multivariate analysis, AUC ratio and
      time to reach target temperature were significantly influenced by BSA (p < 0.01)
      and meperidine (p < 0.05); AUC-34 was influenced only by BSA (p < 0.01). The AUC
      35 was influenced by BSA (p < 0.01), shivering, and total meperidine dose (p <
      0.05). CONCLUSIONS: The most important determinant of effective cooling during
      endovascular hypothermia is BSA; larger patients are more difficult to cool and
      maintain in therapeutic range. Older patients cool more quickly. Shivering was
      well controlled by the combination of meperidine, buspirone, and surface counter
      warming and only minimally influenced cooling effectiveness. Future trials of
      therapeutic hypothermia may include added measures to cool larger patients more
      effectively.

PMID- 22466972
TI  - Immobilization of beta-glucosidase in fixed bed reactor and evaluation of the
      enzymatic activity.
AB  - Adsorption of beta-glucosidase from almonds, an enzyme with big molecular size
      (130 kDa, 6.7 nm molecular diameter), on mesoporous SBA-15 silica in fixed bed
      column was studied. Previously, zeta potential analysis confirmed that the
      electrostatic interactions between beta-glucosidase and SBA-15 were the driving
      force of the immobilization process. The maximum difference in the zeta potential
      was 25 mV at pH 3.5. Adsorption isotherm was classified as an L3 (Langmuir type
      3) curve according to the Giles classification and fitted to a double Langmuir
      equation. The adsorbed amount in a fixed bed column was around 3.5 times higher
      than the amount reached in the adsorption in batch. In addition, the beta
      glucosidase was strongly immobilized on SBA-15 with only 7 % of leaching in the
      washing step with buffer solution. Immobilized beta-glucosidase was catalytically
      active in a continuous process, reaching 100 % substrate conversion and
      maintaining this activity level for more than 10 h without deactivation of the
      enzyme. Adsorption-desorption isotherms at 77 K before and after the adsorption
      were carried out, concluding that the adsorption of beta-glucosidase was produced
      blocking the pore mouth, so that a part of the enzyme penetrates inside and
      another part stays outside the pore.

PMID- 22466973
TI  - Ensuring safety of biosimilar low-molecular-weight heparins: a consensus
      statement of the International Union of Angiology .

PMID- 22466975
TI  - Common haplotype of interleukin-6 gene is associated with chronic total
      occlusions of coronary arteries.
AB  - AIM: Genetic polymorphisms in genes coding for cytokines may predispose patients
      to coronary artery disease and chronic total occlusion (CTO) of coronary
      arteries. The aim of the study was to evaluate association of common genetic
      variations of interleukins (IL) with CTOs. METHODS: We reviewed coronary
      angiograms and evaluated presence of CTOs in 684 consecutive patients with no
      history of revascularization. The following genetic variations were analyzed: IL
      1B +3954 C>T, IL-1B -511 C>T, IL-1RN VNTR and haplotypes of IL-6 encompassing IL
      6 -596 G>A, IL-6 -572 G>C, IL-6 -373 AnTn and IL-6 -174 G>C polymorphisms.
      RESULTS: In 254 patients (37.1%) CTO of at least one artery was found. We
      observed nine IL-6 haplotypes, of which five were common (>1%) and one (GG9/12G,
      n=8) was not previously reported in literature. The most prevalent IL-6 haplotype
      (AG8/12C or Hap*1, 49.5%) correlated with CTOs, that were present in 31.5%, 36.5%
      and 44.5% of patients with none, one and two Hap*1, respectively (OR [95%CI]
      1.252 [0.844-1.856] and 1.746 [1.104-2.762] for heterozygots and homozygots,
      respectively). In multivariate analysis this association became non-significant
      (OR [95%CI] 1.202 [0.805-1.796] and 1.529 [0.955-2.450]). In subgroup analysis
      Hap*1 was, however, associated with CTOs in the left anterior descending artery
      (p for trend 0.032) and the left circumflex artery (P=0.047), but not in the
      right coronary artery (p=0.799). In multivariate analysis CTOs of the left
      coronary arteries were associated only with total cholesterol (OR [95%CI] 1.170
      [1.020-1.341]) and Hap*1 (OR [95%CI] 1.469 [0.914-2.361] and 1.970 [1.151-3.372]
      for heterozyogots and homozygots, respectively). CONCLUSION: Our study suggests
      that common IL-6 haplotype (AG8/12C or Hap*1) is associated with development of
      CTOs in left coronary arteries.

PMID- 22466974
TI  - Epidemiology of chronic venous disorders in geographically diverse populations:
      results from the Vein Consult Program.
AB  - AIM: The Vein Consult Program is an international, observational, prospective
      survey aiming to collect global epidemiological data on chronic venous disorders
      (CVD) based on the CEAP classification, and to identify CVD management worldwide.
      The survey was organized within the framework of ordinary consultations, with
      general practitioners (GPs) properly trained on the use of the CEAP
      classification. METHODS: Screening for CVD was to be performed by enrolling in
      the survey all consecutive outpatients >18 years whatever the reason for
      consultation, to record patient's data and classify them according to the CEAP,
      from the stage C0s to C6. The program enrolled 6232 GPs 91545 subjects were
      analysed. Their mean age was 50.6+/-16.9 years, younger patients being in the
      Middle East and older ones in Europe, and the proportion of women was higher than
      that of men. RESULTS: The worldwide prevalence of CVD was 83.6%: 63.9% of the
      subjects ranging C1 to C6, and 19.7% being C0s subjects. C0s patients were more
      frequently men whatever the age and the geographical zone. C1-C3 appeared to be
      more frequent among women whatever the country but the rate of severe stages (C4
      C6) did not differ between men and women. GPs consider CVD subjects as patients
      eligible to specialist referral beginning from C2 but some geographical
      disparities were observed. CONCLUSION: The VCP survey provides reliable results
      on CVD global epidemiology and shows that CVD affects a significant part of the
      populations worldwide, underlining the importance of adequate screening for CVD
      and training of both GPs and specialist physicians.

PMID- 22466976
TI  - Detecting diabetes and impaired glucose tolerance in patients with
      atherosclerotic peripheral arterial disease.
AB  - AIM: In patients with peripheral arterial disease (PAD), diabetes mellitus is
      associated with increased mortality rates. The aim of this study was to estimate
      the prevalence of undiagnosed diabetes in PAD patients, and to assess whether a
      glucose tolerance test is more sensitive than a simple fasting glucose
      measurement for diagnosis in this group. METHODS: A standard glucose tolerance
      test and fasting glucose measurements were performed in 53 patients with PAD, who
      were then categorised into diagnostic groups according to each test result.
      RESULTS: Using the glucose tolerance test results, 11.5% of patients were
      diagnosed with diabetes mellitus and 28.8% had either impaired fasting glucose or
      impaired glucose tolerance. Using fasting glucose levels only, 7.7% received a
      diagnosis of diabetes mellitus and 17.3% had impaired fasting glucose. The
      glucose tolerance data and the fasting glucose data were in agreement in 82.7% of
      cases, but the glucose tolerance test identified an additional 3.8% of cases with
      diabetes and an additional 13.5% of cases with impaired glucose tolerance.
      CONCLUSION: Undiagnosed diabetes and impaired glucose homeostasis are common in
      patients with PAD. Routine screening using a simple glucose tolerance test should
      be considered in the clinical assessment of this group.

PMID- 22466977
TI  - Three-dimensional contrast-enhanced magnetic resonance angiography at 3.0T
      scanner: significance in the classification of peripheral arterial occlusive
      disease.
AB  - AIM: Aim of this study was to evaluate the clinical efficacy of three-dimensional
      contrast-enhanced magnetic resonance angiography (3D CE-MRA); at 3.0T scanner in
      the classification of peripheral arterial occlusive disease (PAOD). METHODS:
      Thirty-five patients diagnosed of PAOD underwent 3D CE-MRA, 30 cases underwent
      digital subtracted angiography (DSA) successfully, and 12 cases underwent
      surgery. RESULTS: The vascular tree from the distal aorta to the lower limbs was
      well demonstrated. The extent and grade of disease seen in 3D CE-MRA closely
      matched those seen in DSA and/or surgery. Compared to the results of DSA and/or
      surgery, the common coincidence of 3D CE-MRA in diagnosing PAOD was 96.89%
      (780/805), the coincidence in diagnosing mild, moderate, severe stenosis and
      occlusion was 90.48% (76/84), 87.14% (61/70), 95.77% (68/71), and 98.29%
      (115/117) respectively, the rate of overestimate in mild, moderate, and severe
      stenosis was 5.95% (5/84), 10% (7/70), and 2.82% (2/71) respectively, the rate of
      underestimate in mild, moderate, severe stenosis and occlusion was 3.57% (3/84),
      2.86% (2/70), 1.41% (1/71) and 1.74% (2/115) respectively. CONCLUSION: 3D CE-MRA
      at 3.0T scanner is of great value in the accurate assessment of the
      classification of PAOD; it is a reliable and promising new technique.

PMID- 22466978
TI  - Ankle-brachial index in a type 2 diabetic population with proliferative
      retinopathy: associated risk factors and complications.
AB  - AIM: The aim of this study was to analyse risk factors and complications
      associated with low ankle-brachial index (ABI) in a type 2 diabetic population
      with proliferative retinopathy. METHODS: This study included 181 subjects. ABI
      was measured with a Doppler device. Subjects with ABI <0.9 were diagnosed with
      peripheral vascular disease (PVD). The exclusion criterion was medial arterial
      calcification. RESULTS: The mean (+/- SD) age and diabetes (DM) duration were
      65+/-9.7 years and 18.6+/-9.1 years, respectively. ABI <0.9 was associated with
      increasing age (P<0.001), DM duration (P=0.02), higher total (P=0.02) and LDL
      cholesterol (P=0.035), higher ESR (P=0.04), uric acid (P=0.004) vibration
      perception thresholds (VPT), and lower eGFR (P<0.001). BMI (P<0.001), waist index
      (P=0.01), FPG (P=0.013), HbA1c (P=0.005) and ALT (P<0.001) were significantly
      lower in patients with PVD. Multivariate analysis revealed age (P=0.04), high
      total cholesterol (P=0.038), low BMI (P=0.017), low VPT (P=0 031) and declining
      eGFR (p=0.006) to be independent predictors of PVD. CONCLUSION: Increasing age,
      total cholesterol levels, and VPT, together with declining renal function and
      lower BMI are independent predictors of PVD in a type 2 diabetic population with
      advanced microvascular disease. Knowledge of risk factors will help target
      preventive measures and treatment to subjects most susceptible to PVD.

PMID- 22466979
TI  - Aerobic physical activity based on fast walking does not alter blood pressure
      values in non-dipper essential hypertensives.
AB  - AIM: Walking is a very acceptable form of aerobic exercise. Several trials have
      demonstrated significant benefits of fast walking on the risk factors of
      cardiovascular disease, particularly for hypertension. Aim of our study was to
      assess whether physical activity obtained through fast walking might lead to a
      different reduction of blood pressure levels in hypertensive patients in relation
      to different circadian profile of blood pressure. METHODS: We have enrolled 84
      hypertensive patients, with evidence of stage I hypertension and non-dipper
      nocturnal profile. All subjects underwent a six weeks physical intervention based
      on fast walking, three sessions a week. Main outcome measurements were diurnal,
      nocturnal and 24-h blood pressure levels. RESULTS: After the sixth week of
      physical exercise there was not any significant change in 24-hour mean systolic
      blood pressure and diastolic blood pressure ABPM values when compared to baseline
      (respectively 143.2+/-5.2 vs. 141+/-4.4 and 91.4+/-4.8 vs. 90.1+/-2.5); also no
      differences in heart rate have been found. CONCLUSION: In non-dipper
      hypertensives a light aerobic program of physical activity based on fast walking
      seems to be less effective to reduce blood pressure values, contrary to what has
      been observed in dipper ones.

PMID- 22466980
TI  - Reliability of constant-load treadmill testing in patients with intermittent
      claudication.
AB  - AIM: Constant-load treadmill testing is frequently used to estimate walking
      ability of patients with peripheral arterial disease and to assess changes in
      functional capacity following therapeutic interventions or through disease
      progression. The value of this test has frequently been disputed based on doubts
      concerning its reproducibility. The aim of this study was to investigate the
      reliability of treadmill testing at a speed of 3 km/h and a constant inclination
      of 12%. METHODS: Sixty-eight patients with stable peripheral arterial disease who
      were familiar with treadmill testing underwent two sessions of walking exercise
      at 3 km/h and 12% inclination within three weeks. Initial claudication distance
      (ICD) and maximum walking distance (MWD) on the treadmill as well as reported
      walking distances on level ground at individual speed were recorded. RESULTS:
      Correlation coefficients of 0.8 and within-subject variation coefficients of 15%
      for ICD and 13% for MWD demonstrated low variability of walking distances between
      visits. No learning effects were observed. Intra-class correlation coefficients
      of 0.78 for ICD and 0.83 for MWD proved good reproducibility of treadmill
      testing. Correlation of measured and reported walking distances was poor.
      CONCLUSION: Constant-load treadmill testing at 3km/h and 12% inclination is a
      well reproducible method to investigate walking capacity of patients with stable
      intermittent claudication who are familiar with this test method. From treadmill
      walking distances, no conclusions should be drawn concerning the actual walking
      range of the patient.

PMID- 22466981
TI  - Does patency after a vein collar and PTFE-bypass depend on sex and age? Re
      analysis of a randomised trial.
AB  - AIM: Randomized studies evaluating the effect of a vein collar at the distal
      anastomosis of PTFE-grafts show conflicting results. The study of the Joint
      Vascular Research Group (JVRG) of UK found improved primary patency while the
      Scandinavian Miller Collar Study (SCAMICOS) found neither any effect on patency
      nor on limb salvage after bypass to below-knee arteries. However, the
      Scandinavian patients were a decade older and predominately female compared to
      the British patients. Can this explain the conflicting result? METHODS: Primary
      patency with respect to sex, age and the use of vein collar were re-analysed in
      345 patients from SCAMICOS with Kaplan-Meier life-table technique, log-rank test
      and Cox proportional hazards regression to evaluate any interaction between sex
      or age and the effect of a vein collar on the primary patency rate. RESULTS:
      Females had better patency than males (log-rank test, chi2=9.4, df=1, P=0.002)
      but age had no influence on patency (log-rank test, chi2=3.3, df=3, P=0.35).
      However, 47% of the males compared to 23% of the females were smokers
      (P=0.00002). No interaction effect between sex and vein collar (P-value=0.224) or
      age and vein collar (P-value=0.527) was established. CONCLUSION: The difference
      between the two randomised vein collar studies are unlikely to depend on the
      disparity in sex and age of the study populations.

PMID- 22466982
TI  - Extreme endovascular revascularization for limb salvage in critical limb
      ischemia.
AB  - AIM: Distal bypass has been considered as a primary choice for the treatment of
      critical limb ischemia (CLI). When bypass failed with limb threatening ischemia,
      the amputation rate is high in patients with increased surgical risks and lack of
      conduit. Percutaneous transluminal angioplasty (PTA) has been shown to be
      effective and safe in the setting of CLI even in patients with failed bypass
      graft. The aim of this study was to review our experience and results of extreme
      endovascular revascularization in patients with CLI following occluded lower limb
      bypass graft. METHODS: Retrospective review from January 2005 to June 2008 of
      patients with CLI following occluded bypass graft who underwent PTA was
      performed. All patients were studied by Duplex scanning and dual-energy computed
      tomographic angiography (DE-CTA) bone removal technique. Stents were used in
      cases of residual stenosis or dissection. Technical success was defined as a
      residual stenosis less than 30%. Demographics, comorbidities, functional status,
      details of the procedure information were recorded. Descriptive, logistic
      regression and life-table analyses performed. RESULTS: Thirty-six patients with
      occluded bypass grafts were treated. The mean age was 69 years (range 56-89), 44%
      were older than 80 years, 83% had diabetes mellitus, 88% of limbs treated had
      multiple lesions included Tasc C and D lesions. Technical success was achieved in
      91%. Mean follow-up was 24 months. At follow-up, there were 19 PTA failures which
      were followed by subsequent procedures: redo PTA in 16 limbs, redo bypass in 2,
      amputation in 5. Cumulative primary patency was 60% (+/-0.08 SE) and 24% (+/-0.07
      SE). Secondary patency was 96% (+/-0.03 SE) and 83% (+/-0.08 SE). Limb salvage
      was 84% (+/-0.06 SE) and 70% (+/-0.10 SE). Freedom from surgical revision was 78%
      (+/-0.07 SE) and 54% (+/-0.11 SE). Overall survival was 89% (+/-0.05 SE) and 58%
      (+/-0.11 SE) at 12 and 24 months, respectively. CONCLUSION: Endovascular
      revascularization of patients with CLI and occluded bypass graft is a safe and
      feasible procedure with reasonable technical and clinical success and limb
      salvage. PTA may be the only alternative to amputation in these patients with
      extensive comorbidities and limited life expectancy.

PMID- 22466983
TI  - Factors influencing the recanalisation rate of deep venous thrombosis .
AB  - AIM: After an acute episode of deep venous thrombosis (DVT) resolution of venous
      thrombi is followed. However, the complete recanalisation occurs only in about a
      half of the patients. Therefore, the disease is accompanied by different
      sequellae like post-thrombotic syndrome. Factors that contribute to lysis of
      thrombi remain poorly understood. Therefore, the aim of our study was to
      investigate whether levels of the circulating inflammatory markers and other
      factors like fibrinolytic parameters, sex, and extent of the thrombotic occlusion
      are related to the recanalisation rate. METHODS: The study included 49 patients
      with idiopathic DVT in the stable phase of the disease (4-6 months after the
      diagnosis). All patients were evaluated for the presence of risk factors of
      atherosclerosis. Using Duplex ultrasound patients were examined in acute phase of
      the disease (before start of treatment), and at the end of the observation period
      (after 4 to 6 months). Each affected venous segment was classified as completely
      recanalised, partially obstructed, or completely occluded. Blood was collected
      for laboratory analysis of the fibrinolytic activity and circulating inflammatory
      markers. RESULTS: Complete recanalisation occurred more frequently in distal
      (popliteal) than in proximal venous thrombosis (57% vs. 43%, P<=0.01), and the
      recanalisation rate was lower in patients with more extended thrombosis
      (increased thrombus load). The recanalisation rate (partial and total) was higher
      in females than in males: 87% vs. 73%, P=<0.05. Risk factors of atherosclerosis
      had no influence on the recanalisation rate of the occluded deep veins. Out of
      the endogenic fibrinolytic markers, t-PA activity only was significantly related
      to the recanalisation rate. The recanalisation was shown to be related to some
      circulating cytokines. The multivariate analysis, including inflammatory markers
      and the recanalisation of deep veins as dependent variables showed that IL-6 and
      P-selectin were the only statistically significant independent predictors of the
      recanalisation rate. CONCLUSION: The results of our study show that 4 - 6 months
      after an acute episode of DVT complete recanalisation of the occluded veins
      occurred in about 50%. The recanalisation rate is related to the extent of venous
      thrombosis, is lower in proximal occlusions and is higher in females than in
      males. In patients with increased cytokine levels and decreased t-PA activity
      recanalisation is less likely.

PMID- 22466984
TI  - Plasminogen activator inhibitor-1 levels in patients with primary varicose vein.
AB  - AIM: Plasmin is involved in extracellular matrix remodeling by activating some
      matrix metallo-proteinases and degrading extracellular matrix; therefore
      component of fibrinolytic system such as tissue plasminogen activator and
      plasminogen activators inhibitors (PAI-1) might have a role in the pathogenesis
      of vascular remodeling. In our study we aimed to investigate the levels of PAI-1
      levels in patients with primary varicose veins (VV) and in their age and gender
      matched control group. METHODS: Forty-one consecutive patients with peripheral
      varicose veins and 37 healthy age and gender-matched control subjects were
      included in the study from the outpatient cardiology and cardiovascular surgery
      clinic. Study population consisted of 41 consecutive patients who met the
      inclusion criteria and diagnosed as having class II primary VV according to CEAP
      classification. Routine biochemical and hematological analysis were performed in
      all patients and control subjects. RESULTS: Plasma levels of PAI-1 were found to
      be lower in patients than those in control subjects (5.19+/-2.2 ng/mL vs. 6.47+/
      2.6 ng/mL, P=0.025). Logistic regression analysis revealed that only the plasma
      levels of PAI-1 were found to be independently but inversely associated with the
      presence of primary VVs (Odds ratio: 0.80 CI: 0.64-0.99, P=0.04). CONCLUSION: We
      have shown that PAI-1 levels are significantly decreased in patients with pVVs
      and it has an independent association with the presence of pVVs. However, its
      exact relation and role via matrix metlalloproteinases on the pathogenesis of the
      disease remains to be elucidated in further studies.

PMID- 22466985
TI  - Growth rates of abdominal aortic aneurysms in Japanese patients observed in one
      institute.
AB  - AIM: The aim of this paper was to investigate the growth rate of abdominal aortic
      aneurysms (AAA) in Japanese patients. METHODS: We retrospectively studied
      patients conservatively followed with infrarenal AAA in terms of AAA diameter
      measured using computed tomography (CT) in our hospital between 1999 and 2009.
      The AAA surgery criterion in our institute was a diameter >= 5.0 cm or a growth
      rate >=5 mm/year. We estimated operation-free ratios by initial AAA diameter and
      changes in AAA growth rates. Patients with an initial AAA diameter < 5.0 cm were
      divided into 2 groups. Patients with AAA that met the criteria for surgery were
      classified into the expansion group, and those remaining into the non-expansion
      group. Their AAA growth rates were compared. RESULTS: The group consisted of 124
      patients (average age, 73.7+/-8.6 years (range 54-92)) who had at least 2
      recorded AAA measurements. The average follow-up period was 3.0+/-2.2 years
      (range 0.3-10.2). There were no cases of rupture during follow-up. Twenty-six
      patients (21.0%) underwent surgery (open replacement [N.=20]; endovascular
      abdominal aneurysm repair [N.=6]). The growth rate determined from the initially
      measured diameter was significantly faster in AAAs measuring 5.0-5.4 cm than in
      AAAs measuring 4.5-4.9 cm (P=0.01). More than 90% of patients with an initial AAA
      diameter <5.0 cm were observed conservatively for 2 years or more. However, more
      than half of the patients with an initial AAA diameter >=4.0 cm needed surgery
      within 5 years. The growth rates of AAAs for each size during growth were
      significantly faster when the AAA diameter was 4.5-4.9 cm than when it was 4.0
      4.4 cm (P=0.006), and when the AAA diameter was 5.0-5.4 cm than when it was 4.5
      4.9 cm (P = 0.009). The expansion and non-expansion groups consisted of 38
      (34.2%) and 73 (75.8%) patients, respectively. The AAA growth rate in the
      expansion group was significantly faster than that in the non-expansion group
      (3.4+/-2.2 mm/year vs. 1.4+/-1.3 mm/year, P=0.0001). CONCLUSION: It may be
      considered that the appropriate indication for AAA repair is defined by a
      diameter of 5.0 cm for Japanese patients. Patients with AAA that is growing
      continuously by >=3 mm/year and who have low operative risk may undergo surgery
      even if their AAA is <5.0 cm.

PMID- 22466986
TI  - Flow patterns and preferred sites of intimal thickening in bypass-grafted
      arteries .
AB  - AIM: In bypass-grafted arteries, anastomotic intimal hyperplasia develops more
      markedly at the distal junction than the proximal one. It is likely that it
      arises from the difference in flow patterns at these two sites. Therefore we have
      studied the relationship between the flow patterns and precise locations of wall
      thickening specific to the particular vessel. METHODS: In total 30 bypass
      grafting procedures were carried out on the femoral arteries of dogs with 10
      autologous common carotid arteries and 20 saphenous veins. The vessels were
      harvested at 3 months after operation, and precise locations of intimal
      thickening and characteristics of the flow such as flow patterns and
      distributions of fluid velocity and wall shear stress were studied in detail.
      RESULTS: At the proximal anastomosis, a large recirculation zone was formed only
      at the inlet of the partially or totally occluded host artery, whereas at the
      distal anastomosis, it was formed at both the floor of the host artery and the
      toe of the bypass in most vessels, and the former was connected to the latter,
      extending the region of disturbed flow to lateral walls of the host artery. Wall
      thickening was found mainly in these regions occupied with slow secondary and
      recirculation flows where wall shear stress was very low. CONCLUSION: The flow at
      the distal anastomosis is more disturbed and complex than that at the proximal
      anastomosis. This difference in flow pattern that determine the region of low
      wall shear stress might explain why intimal hyperplasia develop more markedly at
      the distal junction.

PMID- 22466987
TI  - Cystic adventitial disease of the popliteal artery: a recurrent case after cyst
      wall excision .
AB  - Although atherosclerosis remains the most common cause of lower limb ischemia,
      cystic adventitial disease (CAD) must be considered in the differential diagnosis
      of a patient without risk factors for atherosclerosis. The disease typically
      produces lower limb claudication and usually affects young and middle-aged men.
      The treatment consists of interposition grafting in cases with an occluded
      artery, but the treatment of stenotic lesions without arterial occlusion is
      controversial whether evacuation with cyst wall excision or interposition
      grafting. We report a case of CAD of the popliteal artery in a 70-year-old man
      with recurrence two years after cyst wall excision. This case suggests that
      complete cyst wall excision and regular follow-up are crucial in the management
      of stenotic lesion with CAD.

PMID- 22466988
TI  - Diagnosis and monitoring of cardiac sarcoidosis with delayed-enhanced MRI and 18F
      FDG PET-CT.

PMID- 22466989
TI  - Quantitative Nuclear Cardiology: we are almost there!

PMID- 22466991
TI  - Interview with Yoshinori Yamamoto.

PMID- 22466990
TI  - Reproductive characteristics of stallions during the breeding and non-breeding
      season in a tropical region.
AB  - The objective of this study was to investigate reproductive characteristics of
      stallions at a tropical zone in the breeding and non-breeding seasons. The
      following parameters were assessed: testicular volume; semen quality; and serum
      concentrations of LH, FSH, and testosterone; in addition to the percentages of
      germ cells and proportions of germ cells/Sertoli cells by testicular cytology in
      stallions. Semen was collected from eight adult stallions twice a week during a
      12-week period in both seasons (6 weeks before and 6 weeks after the summer and
      winter solstices). Jugular blood samples were collected periodically for hormone
      analysis by radioimmunoassay during the same periods. Testicular measures and
      cytological samples were taken at the end of each period. Mean concentration of
      testosterone was significantly higher (P = 0.04) during the breeding season and
      the proportion of Sertoli cells/100 germ cells in cytological smears was
      significantly lower during the breeding season (P = 0.0001). Effects of season
      were not significant either for testicular volume or for any semen parameter (P >
      0.05). Seasonal changes in the mean concentrations of LH and FSH were not
      observed (P > 0.05). There were also no significant differences in the mean
      percentages of germ cell types between both seasons (P > 0.05). Lack of seasonal
      differences in the testicular volume and semen parameters of tropical stallions
      are probably due to the small variation in duration of natural light between the
      observed periods, slightly under 3 h.

PMID- 22466992
TI  - Preliminary experience with a new device for delayed sternal closure strategy in
      cardiac surgery.
AB  - PURPOSE: Open chest management with delayed sternal closure (DSC) is a valuable
      strategy in the management of patients with postcardiotomy hemodynamic
      instability or severe coagulopathy. The conventional extemporized material
      available for off-label sternal stenting however may limit its efficacy. We
      evaluated outcomes of patients with refractory severe postcardiotomy cardiogenic
      shock (SPCCS) treated with DSC using a novel temporary sternal spreader (NTSS)
      which allows myocardial recovery by progressive controlled approximation of the
      sternal edges. METHODS: Seven patients (4 male, mean age 66.5 +/- 5 years) with
      refractory SPCCS showing acute hemodynamic instability at sternal closure, were
      implanted with the NTSS, consisting of stainless-steel branches linked to 2
      diverging plates of polyether-ether ketone, whose progressive opening/closing
      mechanism can be controlled from outside the chest with a rotating steel wire.
      The sternal wound was closed by an elastic membrane to achieve a sterile field.
      Swan-Ganz monitoring was employed, and clinical outcomes evaluated. RESULTS: The
      device was successfully implanted in all patients without device-related
      complications or failures. Progressive approximation of sternal edges, titrated
      on cardiac index values, was successfully completed allowing subsequent
      uneventful sternal closure in all. Mean time from SPCCS to sternal closure was 70
      +/- 21 hours. No patient developed infective complications or late hemodynamic
      instability after device removal and sternal closure. One patient (14%) died of
      multiorgan failure on postoperative day 9. CONCLUSIONS: Despite the limited
      number of patients enrolled, the NTSS proved safe and effective in allowing
      complete myocardial recovery after SPCCS, avoiding hemodynamic instability
      related to abrupt sternal closure, with no occurrence of infective complications.

PMID- 22466993
TI  - New optimum humanoid hand design for prosthetic applications.
AB  - To address the need for a commercially feasible prosthetic hand, the current work
      presents the design of a new humanoid hand actuated using shape memory alloy
      (SMA) artificial muscle wires. The hand has 3 compliant fingers and a thumb
      attached to the palm. The palm structure is a novel design, which is based on the
      natural arches of the human hand to provide better grasping capabilities. A
      compact actuator module is proposed to house and cool the SMA wires. Design
      parameters of the hand were selected to maximize the work density. The hand is
      lightweight, low cost, and operates silently. It has functional opening and
      closing speeds and fingertip force. 

PMID- 22466994
TI  - Extracellular volume expansion in peritoneal dialysis patients.
AB  - INTRODUCTION: Cardiovascular mortality remains high among peritoneal dialysis
      (PD) patients. Several small studies have suggested that PD patients are volume
      expanded, and as such this could be a cardiovascular risk factor. We therefore
      wished to investigate factors which could lead to extracellular water (ECW)
      expansion. METHODS: Retrospective cross-sectional audit of 600 prevalent, adult
      PD patients attending two tertiary university PD centers, with corresponding
      assessments of PD adequacy, transport status, and multifrequency bioimpedance
      measurements of extracellular water to total body water (ECW/TBW). RESULTS: 600
      PD patients, median age 57.5 (46.9-67.9) years, 54% male, 31% diabetic, 47.6%
      Caucasoid, median PD vintage 16 (3.7-38) months, (64% prescribed icodextrin, 34%
      hypertonic glucose dialysates, and 74% antihypertensive medications). Mean ECW
      15.1+/-0.2 L, ICW 20+/-0.2 L, ECW/TBW ratio 0.437+/-0.007. On multivariate
      analysis %ECW/TBW was associated with age (F=13.1 beta=0.045 p=0.000), number of
      antihypertensive medications (F=10.3 beta=0.43 p=0.001), log CRP (F=12.9 beta=1.3
      p=0.000), and negatively with serum albumin (F=25 beta=-0.22 p=0.000), and
      residual renal function (urine volume mL F=9.96 beta=-0.001 p=0.002) (weekly
      Kt/Vurine F=8.82 beta=-2.05, p=0.003). CONCLUSIONS: Overhydration as assessed by
      ECW/TBW is prevalent in adult PD patients, and is associated with loss of
      residual renal function, inflammation, malnutrition and hypertension - as
      assessed by antihypertensive medications. As this was a retrospective cross
      sectional audit, whether loss of residual renal function, inflammation, and
      protein energy wasting lead to volume expansion remains to be determined in
      prospective longitudinal studies.

PMID- 22466995
TI  - Toward the optimal dose metric in continuous renal replacement therapy.
AB  - PURPOSE: There is no consensus on the optimal method to measure delivered
      dialysis dose in patients with acute kidney injury (AKI). The use of direct
      dialysate-side quantification of dose in preference to the use of formal blood
      based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has
      been recommended for dose assessment in critically-ill patients with AKI. We
      evaluate six different blood-side and dialysate-side methods for dose
      quantification. METHODS: We examined data from 52 critically-ill patients with
      AKI requiring dialysis. All patients were treated with pre-dilution CVVHDF and
      regional citrate anticoagulation. Delivered dose was calculated using blood-side
      and dialysis-side kinetics. Filter function was assessed during the entire course
      of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12
      hours. RESULTS: Median daily treatment time was 1,413 min (1,260-1,440). The
      median observed effluent volume per treatment was 2,355 mL/h (2,060-2,863)
      (p<0.001). Urea mass removal rate was 13.0 +/- 7.6 mg/min. Both EKR (r2=0.250;
      p<0.001) and KD (r2=0.409; p<0.001) showed a good correlation with actual solute
      removal. EKR and KD presented a decline in their values that was related to the
      decrease in filter function assessed by the FUN/BUN ratio. CONCLUSIONS: Effluent
      rate (mL/kg/h) can only empirically provide an estimated of dose in CRRT. For
      clinical practice, we recommend that the delivered dose should be measured and
      expressed as KD. EKR also constitutes a good method for dose comparisons over
      time and across modalities.

PMID- 22466996
TI  - Spontaneous breathing of heliox using a semi-closed circuit: a bench study.
AB  - INTRODUCTION: The use of helium-oxygen mixture (heliox) for ventilation has an
      advantage in patients with obstruction of the airways. The physical properties of
      helium enable an easier gas flow through the airways; this enables easier
      breathing for the patient when compared to standard ventilation of air. A high
      cost of heliox falls within the factors that limit the use of heliox in clinical
      practice. At present, heliox is administered by use of an open circuit. The aim
      of this study is to propose a way of heliox administration that reduces heliox
      consumption but does not affect the positive heliox effects upon the airway
      resistance. METHODS: To minimize consumption of heliox, a semi-closed circuit has
      been designed. The circuit is a modification of an anesthetic circuit composed of
      parts with the lowest possible resistances. As any circuit has its own
      resistance, the evaluation of its possible negative effect upon the work of
      breathing of patients with exacerbation of chronic obstructive pulmonary disease
      (COPD) has been conducted. RESULTS: A semi-closed circuit for heliox
      administration has been constructed and evaluated. The intrinsic resistance of
      both the inspiratory and expiratory limbs of the circuit is less than 140 Pa.s/l.
      This resistance does not represent a significant workload for a patient with COPD
      exacerbation whose airway resistance is 10 to 20 fold higher. CONCLUSIONS: The
      designed semi-closed circuit offers a potential benefit of heliox in patients
      with COPD exacerbation.

PMID- 22466997
TI  - The effects of pulsatile cardiopulmonary bypass on acute kidney injury.
AB  - PURPOSE: Protective effect of pulsatile flow cardiopulmonary bypass (CPB) on the
      occurrence of acute renal injury is still a matter of debate. The objective of
      this study was to compare the effects of pulsatile and non-pulsatile
      cardiopulmonary bypass on kidneys using Urinary neutrophil gelatinase-associated
      lipocalin (NGAL) and interleukin-18 (IL-18) as the markers of renal injury.
      METHODS: 85 consecutive patients with normal preoperative renal function were
      prospectively enrolled in the study. Pulsatile perfusion (Group P) and non
      pulsatile perfusion (Group NP) was used in 42 and 43 of the patients,
      respectively, during aortic cross-clamping period. NGAL and IL-18 were analyzed
      using ELISA in urine samples obtained preoperatively, and at 2, 12, and 24 h
      after CPB. RESULTS: There was no significant difference between the groups in
      terms of perioperative renal function tests. IL-18 levels measured at 12 h after
      CPB were significantly lower in Group P, compared to Group NP (p<0.05). Urinary
      NGAL levels measured at 2 and 12 h were higher in Group NP; however, the
      difference was insignificant. In the subgroup of patients with a cross clamp time
      >=45 minutes (pulsatile CPB, group P1, n = 33; non-pulsatile CPB, group NP1, n =
      33), IL-18 levels measured at 12 hours after CPB were significantly lower in
      Group P1. Urinary NGAL concentrations measured at 2 and 12 hours in Group P1 were
      also significantly lower than that in Group NP1 (p = 0.048 and 0.043,
      respectively). CONCLUSIONS: Low IL-18 and NGAL levels found in the pulsatile
      perfusion group might suggest the use of pulsatile flow resulted in better kidney
      protection.

PMID- 22466998
TI  - In vitro investigations of citrate clearance with different dialysis filters.
AB  - OBJECTIVE: In extracorporeal blood purification, citrate anticoagulation offers
      several substantial advantages over conventional heparin anticoagulation.
      However, there is still a lack of information on citrate kinetics, especially on
      the citrate clearance of conventional hemodialyzers. The aim of this study was to
      investigate the citrate clearance for different hemodialysis filters as a basis
      for the development of an intelligent citrate-calcium infusion algorithm.
      MATERIALS AND METHODS: For our experiments, the Fresenius 4008H dialysis machine
      and the dialysis filters FX 60, F6 HPS, F8 HPS (Fresenius Medical Care, Bad
      Homburg, Germany), Polyflux 140H and 14L (Gambro Holding, Stockholm, Sweden),
      Xenium 130 (Baxter AG, Vienna, Austria) and APS-650 (ASAHI Kasei Kuraray Medical,
      Chiyoda-ku, Japan) were used. Clearance calculations were performed based on
      plasma/blood flow rate and the citrate concentrations at filter inlet and outlet.
      All experiments were carried out in vitro with fresh frozen plasma (FFP) or whole
      blood. RESULTS: The results prove that citrate clearance is significantly higher
      with high-flux filters than with low-flux filters. Higher dialysate flow rates
      cause a more effective removal of citrate. The citrate clearance for low-flux and
      high-flux filters was 71 +/- 7 and 86 +/- 1% of the urea clearance, respectively.
      CONCLUSIONS: Citrate can efficiently be removed with standard hemodialysis.
      However, depending on the infused amounts as well as on the patient - especially
      in patients with impaired liver function - the use of a high-flux dialysis filter
      and a high dialysate flow rate should be considered to minimize the risk of
      citrate accumulation.

PMID- 22466999
TI  - Synthesis of functional hybrid silica scaffolds with controllable hierarchical
      porosity by dynamic templating.
AB  - We report a facile one-pot synthesis of hierarchically porous scaffolds, with
      independent control over nanoparticle mesoporosity and scaffold macroporosity.
      Our technique combines the chemistry of mesoporous silica nanoparticles with the
      control afforded by dynamic templating of surfactant mesophases. These materials
      are readily functionalizable and allow controllable spatial variation in
      macroporosity.

PMID- 22467000
TI  - Satisfaction and quality-of-life issues in body contouring surgery patients: a
      qualitative study.
AB  - BACKGROUND: Body contouring, which encompasses a range of surgical procedures on
      different areas of the body, is one of the most rapidly growing areas of plastic
      surgery. Little is known about outcomes from the perspective of post-weight loss
      body contouring patients. The aim of our qualitative study was to identify the
      health and aesthetic concerns of such patients through in-depth patient
      interviews. METHODS: Forty-three bariatric surgery post-weight loss body
      contouring patients were recruited between September 2009 and January 2011 from
      the offices of five plastic surgeons located in the USA and Canada. Interviews
      were used to explore the impact that obesity, weight loss, and body contouring
      surgery had on all aspects of the patient's life. Interviews were transcribed and
      data analysis involved coding and the use of the constant comparison method to
      develop categories and themes. Interviewing continued until no new themes
      emerged. RESULTS: Patients described a range of important health and aesthetic
      concerns related to body contouring surgery following massive weight loss,
      including the following: appearance-related concerns, physical health concerns,
      sexual health concerns, psychological health concerns, and social health
      concerns. Body contouring surgery played an instrumental role in the completion
      of the entire weight loss process for patients. CONCLUSIONS: The removal of
      excess skin leads to improvements in a patient's appearance and enhanced
      physical, psychological, and social health and well-being. In order to
      appropriately measure the impact of body contouring procedures from the patient's
      perspective, a well-developed psychometrically sound patient-reported outcome
      instrument is needed.

PMID- 22467001
TI  - Prevalence of overweight in children of obese patients: a dietary overview.
AB  - BACKGROUND: Evidence indicates that eating habits established during childhood
      related to food intake persist when the child becomes an adult. Parental obesity
      is positively associated with the development of obesity in the offspring, who
      tend to become sick and obese young adults during the reproductive phase and end
      up looking for bariatric surgery in order to reverse the non-communicable
      diseases (NCDs) already established. METHODS: This cross-sectional study
      evaluated 40 children aged 0 to 10 years, whose mothers underwent bariatric
      surgery at the Center of Morbid Obesity, Hospital Sao Lucas, Pontificia
      Universidade Catolica do Rio Grande do Sul (COM HSL PUCRS). RESULTS: Among these
      children, 45 % were overweight and 16 had high waist circumference values. The
      total energy intake and sodium consumption were above the Dietary Reference
      Intakes (DRIs) for the age group, while dietary fiber and potassium intakes were
      below DRIs. Obese children had higher percentage of lipid caloric intake (28.3
      vs. 25.3 %, p < 0.025), while the non-obese group tended to have an increased
      consumption of carbohydrate (62.6 vs. 60 %, p < 0.066) when compared to the
      respective DRIs. The presence of NCDs in children's relatives was 100 %.
      CONCLUSIONS: There is probably a significantly higher prevalence of obesity among
      children of morbidly obese parents when compared to the general child population.
      Since the familial aggregation of NCDs was absolute, these results point to the
      need for careful evaluation when dealing with children. However, further studies
      with a larger number of individuals are needed to confirm these results.

PMID- 22467002
TI  - Evidence for the formation of UO2(NO3)4(2-) in an ionic liquid by EXAFS.
AB  - The complexation between uranium(vi) and nitrate ions in a hydrophobic ionic
      liquid (IL), namely [BMI][NO(3)] (BMI = 1-butyl-3-methylimidazolium(+)), is
      investigated by EXAFS spectroscopy. It was performed by dissolution of uranyl
      nitrate UO(2)(NO(3))(2).6H(2)O or UO(2)(Tf(2)N)(2) (Tf(2)N =
      bis(trifluoromethylsulfonyl)imide (CF(3)SO(2))(2)N(-)). The formation of the
      complex UO(2)(NO(3))(4)(2-) is evidenced.

PMID- 22467003
TI  - b-FGF induces corneal blood and lymphatic vessel growth in a spatially distinct
      pattern.
AB  - PURPOSE: To study the spatial variances in ligand expression and angiogenic
      effect in response to the inflammatory response induced by basic fibroblast
      growth factor (b-FGF). METHODS: b-FGF micropellets (80 ng) were implanted in the
      temporal side of the cornea of Balb/c mice. On days 1, 3, and 7, blood (heme-)
      and lymphangiogenesis were observed by immunofluorescence staining of corneal
      flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels,
      respectively. A second group of corneas were harvested for quantitative real-time
      polymerase chain reaction. Each cornea was divided into 2 different areas: (1)
      pre-pellet area and (2) opposite-pellet area. Expression of vascular endothelial
      growth factor (VEGF) ligands was evaluated using real-time polymerase chain
      reaction in each respective zone. RESULTS: Blood vessels grew into the cornea
      from the pre-pellet area, whereas corneal lymphatic vessels grew from the
      opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in
      the pre-pellet, whereas VEGF-D expression was mostly observed in the opposite
      pellet area. VEGF-C level increased simultaneously in both areas. CONCLUSIONS: A
      single inducing factor, that is, b-FGF, may simultaneously provoke
      hemangiogenesis and lymphangiogenesis in different locations of the cornea
      through differential expression of VEGF ligands. This distinctive spatial pattern
      should be considered while evaluating the corneal predilection for inflammation
      beyond that which is directly visible by slit lamp examination.

PMID- 22467004
TI  - Enzyme-assisted deep anterior lamellar keratoplasty-a new method of lamellar
      dissection-a wetlab-based pilot study.
AB  - PURPOSE: To explore the safety of a new technique of lamellar dissection, using
      enzymatic digestion of the corneal stroma and extracellular matrix. METHODS: This
      was a wetlab-based pilot study of hyaluronidase and trypsin-assisted deep
      anterior lamellar keratoplasty (DALK) in cadaveric human corneal tissue. Enzyme
      assisted DALK was performed on 17 tissues. These underwent histologic analysis
      using a pneumatic dissection specimen as control. Rates of perforation and
      Descemet membrane (DM) exposure were recorded by clinical observation and by
      optical coherence tomography in selected cases. Where possible, pre- and
      postsurgical endothelial cell counts were obtained via specular microscopy. Two
      tissues from the same donor were halved, with each half soaked in a different
      solution (Optisol, balanced salt solution, hyaluronidase, and trypsin) for 13.5
      hours to observe maximal effect. RESULTS: Successful exposure of DM was achieved
      in 8 specimens. In the remaining 9, manual dissection was possible to a residual
      depth of 25 to 90 MUm where measured with optical coherence tomography. Three
      tissues had perforation of DM, all via manual maneuvers. No deleterious effects
      on residual host tissue were observed by light microscopy with no significant
      rates of endothelial cell loss in 8 tissues in which a predissection cell count
      was obtainable. The 2 enzymes had differing effects on soaked specimens that were
      reflected intraoperatively. CONCLUSION: Preliminary results of this ex vivo study
      are encouraging that enzymolysis may represent an effective innovation in DALK
      surgery with an acceptable safety profile. Further studies are required to refine
      the technique and application of the enzymes in vivo.

PMID- 22467005
TI  - Extreme windkessel effect can cause right heart failure early after truncus
      repair.
AB  - An infant developed severe right heart failure early after truncal repair with a
      pulmonary homograft. A mechanical obstruction by narrowing could not be
      identified at the homograft or pulmonary arteries. However, functional
      obstruction was caused by an extreme windkessel effect in a massively dilated
      homograft that absorbed rather than transmitted the pulse wave. Effective
      treatment consisted of replacing the dilated homograft by a rigid aortic
      homograft of equal size as the initial homograft. When confronted with
      circulatory failure after allograft placement, the clinician should not only look
      for obstruction by narrowing, but also consider the windkessel phenomenon.

PMID- 22467006
TI  - The anomalous origin of the branch pulmonary artery from the ascending aorta.
AB  - The anomalous origin of one pulmonary artery branch from the aorta (AOPA) is
      rare. We report our single-institution surgical experience with this condition.
      Between January 1994 and February 2011, 17 patients (age: 1 month-25 years) with
      AOPA underwent surgery at our institute. Thirteen patients had an anomalous
      origin of the right pulmonary artery (RPA) while four had an anomalous origin of
      the left pulmonary artery (LPA) from the aorta. In patients with anomalous RPA,
      11 patients had the proximal type and two patients had the distal type of AOPA.
      Four patients had associated Tetralogy of Fallot (TOF). In 14 patients, direct
      implantation into the main pulmonary artery was performed, while three patients
      required interpositon of a graft. There was one operative death due to persistent
      hypoxia in a 7-month old child with TOF and an anomalous LPA from the aorta. At a
      median follow-up of 36.5 months (range: 2-192 months), all 16 survivors were
      asymptomatic. On echocardiography, two patients showed a gradient of 25 and 30
      mmHg across the anastomosis and are being followed up. In our experience, early
      repair of AOPA results in acceptable haemodynamic and anatomic results. Long-term
      survival can be expected with a low incidence of re-operation or re-intervention.

PMID- 22467007
TI  - Aspergillus osteomyelitis of the proximal humerus: a case report.
AB  - Aspergillus osteomyelitis is an extremely rare manifestation of invasive
      aspergillosis. Generally, patients in states of significant immune deficiency are
      very susceptible to invasive aspergillosis. We report a case of Aspergillus
      osteomyelitis of the proximal humerus in an immunocompetent patient that required
      aggressive oral antifungal therapy, surgical debridement, and placement of an
      antifungal-impregnated cement spacer. Subsequently, her shoulder was
      reconstructed using a reverse total shoulder prosthesis The clinical course,
      radiographic findings, histology, and management rationale are presented.

PMID- 22467008
TI  - Biochemical changes in pig serum after ochratoxin A exposure.
AB  - The objective of this study was to investigate the effect of ochratoxin A (OTA)
      on serum biochemical parameters of pigs during subchronic treatment with 300 MUg
      OTA/kg of feed for 30 days. OTA treatment resulted in significantly higher (p <
      0.05) serum levels of creatinine, urea, potassium and alkaline phosphatase, and
      significantly lower levels of glucose and total protein. These changes in serum
      biochemical parameters in treated pigs were indicative of impaired liver and
      kidney function caused by OTA exposure.

PMID- 22467009
TI  - A novel method for automatic identification of motion artifact beats in ECG
      recordings.
AB  - This paper presents a novel method for automatic identification of motion
      artifact beats in ECG recordings. The proposed method is based on the ECG
      complexes clustering, fuzzy logic and multi-parameters decision. Firstly, eight
      simulated datasets with different signal-to-noise ratio (SNR) were built for
      identification experiments. Results show that the identification sensitivity of
      our method is sensitive to SNR levels and acts like a low-pass filter that
      matches the cardiologists' recognition, while the Norm FP rate and PVB FP rate
      keep significantly low regardless of SNR. Furthermore, a simulated dataset
      including random durations of motion activities superimposed segments and two
      clinical datasets acquired from two different commercial recorders were adopted
      for the evaluation of accuracy and robustness. The overall identification results
      on these datasets were: sensitivity >94.69%, Norm FP rate <0.60% and PVB FP rate
      <2.65%. All the results were obtained without any manual threshold adjustment
      according to the priori information, thus dissolving the drawbacks of previous
      published methods. Additionally, the total cost time of our method applied to 24
      h recordings is less than 1 s, which is extremely suitable in the situation of
      magnanimity data in long-term ECG recordings.

PMID- 22467012
TI  - Spatial learning and memory deficit of low level polybrominated diphenyl ethers
      47 in male adult rat is modulated by intracellular glutamate receptors.
AB  - Polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants,
      are extensively diffused in the environment. Of particular concern are the
      reported highly sensitivity of PBDEs in children or developmental animals,
      however, almost no information is available on their potential effects on adults
      and the mechanisms are still unknown. In the present study, we investigated the
      neurotoxic effects of sub-chronic PBDE-47 exposure on adult male Sprague-Dawley
      rats. Thus, PBDE-47, 0.1, 0.5 and 1 mg/kg per day was administered to rats by
      gavage for 30 days. The learning and memory function was tested by Morris water
      maze. Further, in order to explore the potential mechanism, the expression of
      NMDA-receptors was evaluated by using both immunohistochemistry (IHC) and RT-PCR.
      Our results showed that sub-chronic exposure to PBDE-47 produced learning and
      memory deficits in male adult rats. Also, significant decrease in the CA1, CA3
      and dentate gyrus areas of hippocampus affected by all three doses of PBDE-47 on
      the expression of NR(1), NR(2)B and Glu were found by IHC. In addition, the
      evaluation of expression of the NR(1), NR(2)B and NR(2)C showed statistically
      significant decrease in mRNA expression in rats exposed to PBDE-47. These
      findings showed that sub-chronic exposure to PBDE-47 could also induce behavioral
      alterations and the neurotoxic effects might due to the down-regulation
      expression of NMDA receptors. Our data indicated that the possibility of exposure
      of adults to PBDE-47 warranted further studies to characterize their potential
      neurotoxicity.

PMID- 22467011
TI  - Safety assessment of oral photodynamic therapy in rats.
AB  - Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a
      photosensitizer) and visible light to destroy target cells (e.g., malignant,
      premalignant, or bacterial cells). The aim of this study was to investigate the
      response of normal rat tongue mucosa to PDT following the topical application of
      hematoporphyrin derivative (Photogem(r)), Photodithazine(r), methylene blue (MB),
      and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One
      hundred and thirty three rats were randomly divided in various groups: the PDT
      groups were treated with the photosensitizers for 10 min followed by exposure to
      red light. Those in control groups received neither photosensitizer nor light,
      and they were subjected to light exposure alone or to photosensitizer alone.
      Fluorescent signals were obtained from tongue tissue immediately after the
      topical application of photosensitizers and 24 h following PDT. Histological
      changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT
      treatment. Fluorescence was detected immediately after the application of the
      photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in
      all experimental groups at all evaluation time points. The results suggest that
      there is a therapeutic window where PDT with Photogem(r), Photodithazine(r), MB,
      and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria
      without damaging normal oral tissue.

PMID- 22467013
TI  - Sister chromatid exchanges in breast cancer patients who underwent chemotherapy.
AB  - The study aimed to determine the effects of cytostatic and genotoxic drugs used
      to treat breast cancer on sister chromatid exchange (SCE). SCE values were
      examined in 25 female patients with breast cancer in pre-treatment, treatment
      process and remission period as well as in 22 nonsmoker women via peripheral
      blood culture technique. The SCE values of patient and control group were
      analyzed via "Mann-Whitney U test". Whilst SCE values of patient group were 8.25
      +/- 3.67, 10.19 +/- 2.95 and 11.52 +/- 3.33 in pre-treatment, treatment process
      and remission periods respectively, it was 7.01 +/- 1.24 in control group. When
      overall SCE values of patients group in pre-treatment period were compared with
      those of control group, no significant difference was observed (p > 0.05),
      whereas highly significant differences were observed between treatment process
      and remission period of patient groups and control group in terms of SCE values
      (p < 0.01). If patients are exposed to any cytostatic and clastogenic drugs, the
      increase in the exchange values was considered remarkable. These findings
      reinforced the availability of sister chromatid exchange technique in directing
      of treatment and monitoring the genetic abnormalities caused by genomic
      instability which may occur due to the drugs used for treatment.

PMID- 22467014
TI  - Toxicity evaluation of glyphosate agrochemical components using Japanese medaka
      (Oryzias latipes) and DNA microarray gene expression analysis.
AB  - Using glyphosate agrochemical components, we investigated their acute toxicity to
      juvenile Japanese medaka (Oryzias latipes) as well as their toxic impact at gene
      expression level on the liver tissues of adult medaka using DNA microarray. In
      our acute toxicity test, juvenile medaka were exposed for 96 hr to each of the
      following glyphosate agrochemical components: 10~160 mg/l of glyphosate, 1.25~20
      mg/l of fatty acid alkanolamide surfactant (DA), and 12~416 mg/l of a fully
      formulated glyphosate herbicide. As a result, LC(50) values of glyphosate, DA,
      and the glyphosate herbicide were > 160 mg/l, 8.5 mg/l, and 76.8 mg/l,
      respectively. On the other hand, adult male medaka fish were exposed to each of
      the glyphosate agrochemical components for 48 hr at the following concentrations:
      16 mg/l of glyphosate, 0.5 mg/l of DA, and 16 mg/l-glyphosate/0.5 mg/l-DA
      mixture. Interestingly, DNA microarray analysis revealed that there were no
      significant gene expression changes in the medaka liver after exposure to
      glyphosate. Nevertheless, 78 and 138 genes were significantly induced by DA and
      the glyphosate/DA mixture, respectively. Furthermore, we identified five common
      genes that were affected by DA and glyphosate/DA mixture. These results suggested
      that glyphosate itself possessed very low toxicity as previously reported by some
      researchers at least to the small laboratory fish, and the major toxicity of the
      glyphosate agrochemical resided mainly in DA and perhaps in unintentionally
      generated byproduct(s) of glyphosate-DA mixture.

PMID- 22467015
TI  - Determination of dose dependence in repeated dose toxicity studies when mid-dose
      alone is insignificant.
AB  - Repeated dose toxicity studies with rodents are regulatory requirements for
      registering chemical substances like drugs and pesticides with the government
      regulatory agencies. Usually 4 groups of animals, including a control group, are
      used in repeated dose toxicity studies. Williams' test,  Dunnett's test and
      Jonckheere's trend test are generally used to evaluate the data obtained from
      these studies. Selection of a statistical tool is relatively easy, when the data
      obtained from the groups of animals show a dose-dependency. But, occasionally a
      significance difference, compared to control, is not seen in the mid-dose group
      alone, thus losing the dose-dependency. We attempted to find the appropriate
      statistical tool for analyzing the quantitative data obtained from repeated dose
      toxicity studies, when the data of the mid-dose group alone do not show a
      significant difference, compared to control. The commonly used  Williams' test to
      analyse such data has a disadvantage as it assigns an estimated mean value for
      the mid-dose group, rather than the original mean value, for the analysis. Hence,
      it is likely that Williams' test may misjudge in establishing a dose dependency,
      when in reality it does not exists. Therefore, to analyse such data we suggest
      the use of Dunnett's multiple comparison test, to compare each dose group with
      the control, followed by Jonckheere's trend test for examining dose dependency.

PMID- 22467016
TI  - In vitro validation of drug-induced phospholipidosis.
AB  - Intracellular accumulation of phospholipids with lamellar bodies is a hallmark of
      drug-induced phospholipidosis (PLD) which is caused by impaired phospholipid
      metabolism of the lysosome. Although it remains uncertain whether PLD is
      associated with the adverse effects, sponsors generally terminate the development
      of a candidate drug when PLD is observed in an organ. For drugs that are used
      without serious adverse events, there should be labels indicating that the drug
      can induce PLD. We conducted LipidTox and NBD-PE assays for detecting PLD to
      compare and validate the methods. In the case of contrary results in both assays,
      electron microscopy was performed to confirm the data. We selected 12 chemicals
      and divided them into 4 categories: P+S+, PLD and steatosis positive; P+/S-, PLD
      positive and steatosis negative; P-S+, PLD negative and steatosis positive; P-/S
      , PLD and steatosis negative. In general, results showed very good agreement with
      the known information with some minor discrepancies. LipidTox assay is proven to
      be a very sensitive method. Considering the contrary results of acetaminophen and
      menadione in LipidTox and the NBD-PE assay, the combination of two methods using
      different phospholipids is advantageous to reduce false positives. The finding
      that acetaminophen was positive in LipidTos assay and increased the frequency of
      lamellar body implies that acetaminophen is a weak inducer of PLD.

PMID- 22467017
TI  - A tiered approach combining the short time exposure (STE) test and the bovine
      corneal opacity and permeability (BCOP) assay for predicting eye irritation
      potential of chemicals.
AB  - For the evaluation of eye irritation, one in vitro alternative test may not
      completely replace the Draize test. Therefore, a tiered approach combining
      several in vitro assays, including cytotoxicity assays, is proposed in order to
      estimate the eye irritation potential of a wide range of chemical classes. The
      Short Time Exposure (STE) test, a relatively newer alternative eye irritation
      test, involves exposing Statens seruminstitut rabbit cornea (SIRC) cells for 5
      min to two concentrations (5% and 0.05%) of test material. In the present study,
      we examined the predictive capacity of a tiered approach analyzing the results
      from the STE test and then the results of the bovine corneal opacity and
      permeability (BCOP) assay for assessing globally harmonized system (GHS) eye
      irritation rankings of various chemicals. The accuracy of predicting the GHS
      rankings was slightly improved when the tiered approach combination of STE test
      and BCOP assay was used compared to when the STE test irritation rank
      classification was used alone. Moreover, the under prediction rate was
      substantially improved when this tiered approach was used. From these results,
      the tiered approach of combining the data analysis of the STE test and BCOP assay
      might be a promising alternative eye irritation test strategy.

PMID- 22467018
TI  - Estrogen and androgen receptor status in hepatocellular hypertrophy induced by
      phenobarbital, clofibrate, and piperonyl butoxide in F344 rats.
AB  - The present study examined hepatic estrogen receptor (ER) and androgen receptor
      (AR) levels as well as estrogen-signaling status in a model of rat hepatic
      hypertrophy induced by phenobarbital (PB), chlofibrate (CF), or piperonyl
      butoxide (PBO). Male F344 rats were fed with PB at 2,500 ppm, CF at 2,500 ppm,
      and PBO at 20,000 ppm for 3 days, 4 weeks, and 13 weeks. CF and PBO induced
      diffuse hypertrophy, while centrilobular hypertrophy was observed with PB
      administration. The levels of mRNA for ERalpha, AR and leukemia inhibitory factor
      receptor (LIFR) which was found to be estrogen responsive in the present study,
      were determined by quantitative RT-PCR. In the CF and PBO groups, ERalpha mRNA
      expression was reduced, and consequently, the expression of a responsive gene,
      LIFR, was also decreased, while PB had no effect on ER mRNA levels. AR mRNA
      expression decreased in all the treated groups, but reduction was persistent only
      in PB group. Recently, LIFR was identified as a tumor suppressor gene in human
      HCC. Thus, LIFR may be one of the key mediators of hepatic carcinogenesis induced
      by CF and PBO, but PB appears to act via different mechanisms.

PMID- 22467019
TI  - Microarray and gene ontology analyses reveal downregulation of DNA repair and
      apoptotic pathways in diethylstilbestrol-exposed testicular Leydig cells.
AB  - This study investigated the deleterious effects of the synthetic non-steroidal
      estrogen diethylstilbestrol (DES) on testicular Leydig cells and compared these
      effects with those of the natural estrogen 17beta-estradiol (E2). For that
      purpose, we performed microarray analysis of a mouse Leydig cell line (TTE1)
      treated with these estrogens, followed by Gene Ontology (GO) analysis and
      parametric analysis of gene set enrichment (PAGE). Most notably, GO analysis
      revealed a significant decrease in the biological processes of the GO categories
      "DNA repair" and "apoptotic program" in DES-exposed cells. PAGE showed that "cell
      death," which is a superior GO category including apoptosis in the GO tree
      structure, significantly decreased in DES-exposed cells but significantly
      increased in E2-exposed cells. Interestingly, only 2 genes (Tia1 and Gas1) with
      altered expression patterns in the "cell death" category were common between DES-
      and E2-treated cells. The downregulation of apoptotic cell death pathways and DNA
      repair capability of DES-exposed cells implies that DES promotes carcinogenic
      processes more strongly than E2 does. These findings suggest that molecular
      events that occur following DES and E2 treatments differ substantially in Leydig
      cells, and that the effects of synthetic estrogen and natural estrogen differ
      more substantially than previously suspected.

PMID- 22467020
TI  - Liver tumor promoting effect of etofenprox in rats and its possible mechanism of
      action.
AB  - To investigate the liver tumor-promoting effects of etofenprox (ETF), a
      pyrethroid-like insecticide, 6 week-old male F344 rats were given an
      intraperitoneal injection of N-diethylnitrosamine (DEN). After 2 weeks from the
      DEN treatment, 12 rats per group received a powdered diet containing 0, 0.25,
      0.50, or 1.0% ETF for 8 weeks. At the time of 2nd week of ETF administration, all
      animals were subjected to two-thirds partial hepatectomy (PH). One rat per group
      except for the 0.25% ETF group died due to surgical operation of PH. The number
      and area of glutathione S-transferase placental form (GST-P) positive foci
      significantly increased in the livers of DEN-initiated rats given 0.50% and 1.0%
      ETF compared with the DEN-alone group. Quantitative real-time RT-PCR analysis
      revealed that the mRNA expression of phase I enzymes Cyp2b1/2, phase II enzymes
      such as Akr7a3, Gsta5, Ugt1a6, Nqo1 significantly increased in the DEN+ETF
      groups. The immunohistochemistry showed the translocation of CAR from the
      cytoplasm to the nuclei of hepatocytes in the ETF-treated groups. Reactive oxygen
      species (ROS) production increased in microsomes isolated from the livers of ETF
      treated rats, and thiobarbituric acid-reactive substances (TBARS) levels and 8-
      hydroxy-2-deoxyguanosine (8-OHdG) content significantly increased in all of the
      ETF-treated groups and DEN+1.0% ETF group, respectively. The results of the
      present study indicate that ETF has a liver tumor-promoting activity in rats, and
      suggest that ETF activates the constitutive active/androstane receptor (CAR) and
      enhances microsomal ROS production, resulting in the upregulation of Nrf2 gene
      batteries; such an oxidative stress subsequently induces liver tumor-promoting
      effects by increased cellular proliferation.

PMID- 22467021
TI  - Effective induction of oral anaphylaxis to ovalbumin in mice sensitized by
      feeding of the antigen with aid of oil emulsion and salicylate.
AB  - It is important to evaluate the ability of novel proteins in food crops and
      products to elicit potentially harmful immunologic responses, including allergic
      hypersensitivity. We developed a novel mouse model of food allergy involving an
      oral challenge of a protein antigen after feeding of the antigen in combination
      with modulating factors often ingested in daily life, namely, dietary oil
      emulsion and salicylate. In the model, BALB/c mice were sensitized orally for
      three weeks with ovalbumin (OVA) in linoleic acid/lecithin emulsion, followed
      immediately by intraperitoneal injection of sodium salicylate. At the end of the
      sensitization, the incidence of mice positive for serum OVA-specific IgG1 but not
      IgE had significantly increased in the combined-sensitization group. After the 3
      week sensitization, a single or double oral challenge with OVA effectively and
      significantly caused severe anaphylaxis, as compared with the groups sensitized
      with OVA in the emulsion or the vehicle alone. Moderate increase of plasma
      histamine and intestinal abnormality in histology was found only in the combined
      sensitization group. Anaphylaxis symptoms in the sensitized mice were induced
      more by oral challenge than by intravenous challenge, suggesting a critical role
      for the mucosal system. This is the first model for successful induction of oral
      anaphylaxis in mice sensitized by feeding of food protein without adjuvant. It
      will be useful to elucidate the mechanism of food allergy and to detect
      modulating factors of oral allergy at sensitization using this model, which
      simulates real life conditions.

PMID- 22467022
TI  - Lack of promoting effect of titanium dioxide particles on chemically-induced skin
      carcinogenesis in rats and mice.
AB  - Nano-sized titanium dioxide particles (TiO(2)) are widely used in cosmetics,
      sunscreens and food additives. We previously reported that topical application of
      non-coated rutile type TiO(2) did not exhibit a promoting effect on ultraviolet B
      initiated skin carcinogenesis in rats, and that this was likely due to lack of
      penetration of TiO(2) into the epidermis. In the present study, we examined the
      promoting effect of silicone coated TiO(2 )(sTiO(2)) suspended in silicone oil
      and non-coated TiO(2 )(ncTiO(2)) suspended in Pentalan 408 on a two-stage skin
      chemical carcinogenesis model: sTiO(2) suspended in silicon oil forms smaller
      particles than ncTiO(2) suspended in Pentalan because of the smaller sizes of
      aggregates formed. The model used skin carcinogenesis-sensitive human c-Ha-ras
      proto-oncogene transgenic mice (rasH2) and rats (Hras128) and their wild-type
      counterparts and CD-1 mice to test the effects of topical application of TiO(2).
      Animals were initially treated with a single dose of 7,12
      dimethylbenz[a]anthracene (DMBA) and then with 0, 10, or 20 mg sTiO(2) (mice) or
      0, 50, or 100 mg ncTiO(2) (rats). The incidence and multiplicity of skin tumors
      (squamous cell papilloma and carcinoma) did not increase over DMBA alone controls
      in skin carcinogenesis-sensitive mice or rats or wild-type animals. Analysis of
      rat skin indicated that sTiO(2) and ncTiO(2) did not penetrate though either
      healthy or damaged skin. Furthermore sTiO(2) did not penetrate an in vitro human
      epidermis model. Our results indicate that treatment with sTiO(2) or ncTiO(2) did
      not promote skin carcinogenesis in mice or rats, probably due to lack of
      penetration through the epidermis.

PMID- 22467023
TI  - Topical treatment of oral cavity and wounded skin with a new disinfection system
      utilizing photolysis of hydrogen peroxide in rats.
AB  - The present study aimed to evaluate the acute locally injurious property of
      hydroxyl radical generation system by photolysis of H(2)O(2), which is a new
      disinfection system for the treatment of periodontitis developed in our
      laboratory. Firstly, generation of the hydroxyl radical by a test device
      utilizing the photolysis of H(2)O(2) was confirmed by applying an electron spin
      resonance (ESR)-spin trapping technique. Secondly, the bactericidal effect of the
      device was examined under a simulant condition in which Staphylococcus aureus
      suspended in 1 M H(2)O(2) was irradiated with laser light emitted from the test
      device, resulting in substantial reduction of the colony forming unit of the
      bacteria within a short time as 2 min. Finally, acute topical effect of the
      disinfection system on rat oral mucosa and wounded skin was evaluated by
      histological examination. No abnormal findings were observed in the buccal
      mucosal region treated three times with 1 M H(2)O(2) and irradiation. Similarly,
      no abnormal findings were observed during the healing of skin treated with 1 M
      H(2)O(2) and irradiation immediately after wounding. Since topical treatment with
      the novel disinfection technique utilizing the photolysis of H(2)O(2) had no
      detrimental effect on the oral mucosa and the healing of full thickness skin
      wounds in rats, it is expected that the acute locally injurious property of the
      disinfection technique is low.

PMID- 22467024
TI  - Comparison of cytokine profiles in bronchoalveolar lavage fluid of mice exposed
      to respiratory and contact sensitizers.
AB  - Respiratory sensitization to certain low molecular weight chemicals is a big
      concern for workers, but unfortunately there are no validated animal models to
      allow identification of sensitizing chemicals in the environment. In the present
      study, dermally sensitized and intratracheally challenged mice were used to
      investigate effective indicators of respiratory sensitizers. Changes in levels of
      total serum IgE and nine cytokines (G-CSF, IL-4, IL-5, IL-6, IL-12(p70), IL-13,
      IFN-gamma, MCP-1 and TNF-alpha) in bronchoalveolar lavage fluid (BALF) were
      analyzed in BALB/c mice exposed to respiratory sensitizers (phthalic anhydride
      (PA); diphenylmethane-4,4'-diisocyanate (MDI); toluene diisocyanate (TDI);
      chloramine-T (CH); and piperazine (PI)) or contact sensitizers (2,4
      dinitrochlorobenzene (DNCB); and oxazolone (OXA)). Non-sensitized mice were
      treated dermally with solvents and challenged intratracheally with the respective
      test chemicals as solvent controls. Increases in total serum IgE levels were
      observed in all treated mice, with apparent differences in cytokine profiles. PA
      caused statistically significant increases in Th2 cytokines, IL-4, IL-5 and IL
      13, compared with the control. IL-5 was also found to be increased with CH. The
      other three respiratory sensitizers caused statistically significant increases in
      IL-13. In contrast, no change was apparent with contact sensitizers, DNCB and
      OXA, in these Th2 cytokines. Increases in the Th2 cytokines indicate that all
      five respiratory sensitizers induced immune responses in lungs. Interestingly,
      elevation of G-CSF levels in BALF appeared with all five respiratory sensitizers
      but not the two contact sensitizers. The findings suggest that G-CSF could be
      effective to identify respiratory sensitizers in animal models.

PMID- 22467025
TI  - Adolescent hyperactivity of offspring after maternal protein restriction during
      the second half of gestation and lactation periods in rats.
AB  - To clarify the effect of systemic growth retardation on behavior, pregnant rats
      were fed a synthetic diet with either a normal (20% casein) or low (10% casein)
      protein concentration from gestational day 10 to postnatal day (PND) 21 at
      weaning. Offspring were examined for sensory and reflex functions, detailed
      clinical observations, manipulative test, grip strength, motor activity and water
      filled multiple T-maze test. Lowering trend in the air righting reflex index
      during lactation period and a decrease in grip strength on PND 72 were observed
      in the low protein diet group showing suppression of systemic growth. However,
      they were simply the reflection of delayed systemic growth, because parameters on
      impaired reflex function, disturbance of motor function and paralysis were
      unaffected. On the other hand, low protein diet resulted in increased motor
      activity in female offspring. Thus, malnutrition due to maternal protein
      restriction may cause adolescent hyperactivity.

PMID- 22467026
TI  - Sub-acute oral toxicity study with fullerene C60 in rats.
AB  - To obtain initial information on the possible repeated-dose oral toxicity of
      fullerene C60, Crl:CD(SD) rats were administered fullerene C60 by gavage once
      daily at 0 (vehicle: corn oil), 1, 10, 100, or 1,000 mg/kg/day for 29 days,
      followed by a 14-day recovery period. No deaths occurred in any groups, and there
      were no changes from controls in detailed clinical observations, body weights,
      and food consumption in any treatment groups. Moreover, no treatment-related
      histopathological changes were found in any organs examined at the end of the
      administration period and at the end of the recovery period. Blackish feces and
      black contents of the stomach and large intestine were observed in males and
      females at 1,000 mg/kg/day in the treatment group. There were no changes from
      controls in the liver and spleen weights at the end of the administration period,
      but those weights in males in the 1,000 mg/kg/day group increased at the end of
      the recovery period. Using liquid chromatography-tandem mass spectrometry,
      fullerene C60 were not detected in the liver, spleen or kidney at the end of the
      administration period and also at the end of the recovery period. In conclusion,
      the present study revealed no toxicological effects of fullerene C60; however,
      the slight increases in liver and spleen weights after the 14-day recovery period
      may be because of the influence of fullerene C60 oral administration. In the
      future, it will be necessary to conduct a long-term examination because the
      effects of fullerene C60 cannot be ruled out.

PMID- 22467027
TI  - Protective role of intestinal bacterial metabolism against baicalin-induced
      toxicity in HepG2 cell cultures.
AB  - Baicalin, a glycoside present in Scutellaria baicalensis Georgi, is metabolized
      to its aglycone, baicalein, in intestine. In the present study, possible role of
      metabolism of baicalin by intestinal bacteria to baicalein in baicalin-induced
      toxicity was investigated in HepG2 cell cultures. As an intestinal bacterial
      metabolic system for baicalin, human fecal preparation containing intestinal
      microflora (fecalase) was employed. Initially, when cytotoxic effects of baicalin
      and baicalein were compared, baicalin was more cytotoxic than baicalein in HepG2
      cells. When baicalin was incubated with fecalase, it was metabolized to
      baicalein. In addition, baicalin-incubated with fecalase reduced cytotoxicity of
      HepG2 cells in a concentration-dependent manner. Moreover, baicalin-incubated
      with fecalase significantly caused an increase in Bcl-2 expression together with
      a decrease in Bax expression and cleaved Caspase-3. Furthermore, anti-apoptotic
      effect by the incubation of baicalin with fecalase was also confirmed by the
      terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling
      assay. Taken all together, the findings suggested that metabolism of baicalin by
      human fecalase to baicalein might have protective effects against baicalin
      induced toxicity in HepG2 cells.

PMID- 22467028
TI  - Development of humanized steroid and xenobiotic receptor mouse by homologous
      knock-in of the human steroid and xenobiotic receptor ligand binding domain
      sequence.
AB  - The human steroid and xenobiotic receptor (SXR), (also known as pregnane X
      receptor PXR, and NR1I2) is a low affinity sensor that responds to a variety of
      endobiotic, nutritional and xenobiotic ligands. SXR activates transcription of
      Cytochrome P450, family 3, subfamily A (CYP3A) and other important metabolic
      enzymes to up-regulate catabolic pathways mediating xenobiotic elimination. One
      key feature that demarcates SXR from other nuclear receptors is that the human
      and rodent orthologues exhibit different ligand preference for a subset of
      toxicologically important chemicals. This difference leads to a profound problem
      for rodent studies to predict toxicity in humans. The objective of this study is
      to generate a new humanized mouse line, which responds systemically to human
      specific ligands in order to better predict systemic toxicity in humans. For this
      purpose, the ligand binding domain (LBD) of the human SXR was homologously
      knocked-in to the murine gene replacing the endogenous LBD. The LBD-humanized
      chimeric gene was expressed in all ten organs examined, including liver, small
      intestine, stomach, kidney and lung in a pattern similar to the endogenous gene
      expressed in the wild-type (WT) mouse. Quantitative reverse transcription
      polymerase chain reaction (RT-PCR) analysis showed that the human-selective
      ligand, rifampicin induced Cyp3a11 and Carboxylesterase 6 (Ces6) mRNA expression
      in liver and intestine, whereas the murine-selective ligand, pregnenolone-16
      carbonitrile did not. This new humanized mouse line should provide a useful tool
      for assessing whole body toxicity, whether acute, chronic or developmental,
      induced by human selective ligands themselves and subsequently generated
      metabolites that can trigger further toxic responses mediated secondarily by
      other receptors distributed body-wide.

PMID- 22467029
TI  - Trichloroethylene enhances TCR-CD3-induced proliferation of CD8(+) rather than
      CD4(+) T cells.
AB  - Trichloroethylene (TCE) is suspected as a potent immunomodulator that accelerates
      the development of allergic diseases. We previously reported that TCE promotes
      ovalbumin (OVA)-induced active cutaneous anaphylaxis, including enhancing antigen
      specific serum IgE levels and splenic lymphocyte proliferation. However, the
      target cells and molecular mechanism through which TCE modulates antigen-specific
      immune responses remain unclear. To identify a potential underlying mechanism, we
      investigated whether TCE modulates T cell receptor (TCR)-induced T cell
      activation and proliferation in vitro. TCE enhanced T cell proliferation primed
      by anti-CD3 antibody, but not concanavalin A, in a dose-dependent fashion. In
      addition, TCE enhanced anti-CD3-primed proliferation of CD8(+) rather than CD4(+)
      T cells. Consistent with this result, TCE markedly enhanced the Lck
      phosphorylation mediated by anti-CD3 antibody in CD8(+) but not CD4(+) T cells.
      Furthermore, we analyzed the effect of TCE exposure via drinking water for 2
      weeks on splenocyte populations in non-immunized and OVA-immunized mice. In OVA
      immunized mice, TCE (3 mg/l) significantly expanded CD3(+), CD8(+) and CD4(+)
      cell populations, however the effect at the lower concentration was significant
      only in the CD8(+) populations, whereas TCE had no effect on these cells
      population in non-immunized mice. These findings suggest that TCE enhances TCR
      CD3-induced proliferation of CD8(+) rather than CD4(+) cells and disrupts various
      activities of peripheral T cells.

PMID- 22467030
TI  - Enhancement of anti-cholinesterase activity of aqueous samples by hypochlorite
      oxidation for monitoring traces of organophosphorus pesticides in water.
AB  - A reproducible method for monitoring traces of cholinesterase (ChE) inhibitors in
      aqueous samples is described: the method is based on chemical oxidation and a ChE
      inhibition assay. Chlorine was tested as an oxidizing reagent for conversion of
      various thiophosphorus pesticides (P=S compounds) into their P=O analogs, which
      have higher ChE-inhibiting activity. After treating buffered pesticide solutions
      (pH 6.0) with chlorine (final concentration less than 10 mg/l) of at 25 degrees C
      for 15 min, the ChE-inhibiting activities and detection limits for each pesticide
      were determined. Greater ChE-inhibiting activities, leading to lower detection
      limits (ppb levels), were observed for the chlorine-treated solutions fortified
      azinphos methyl, diazinon, isoxathion and ronnel etc. No changes in the ChE
      inhibiting activities were observed for carbamate pesticide solutions tested
      before and after chlorination, but an additive effect showed against ChE when
      these compounds were mixed with paraoxon in water. This combination of oxidative
      derivatization and ChE inhibition assay was applied successfully to the detection
      and determination of ChE inhibitors in natural and drinking water samples.

PMID- 22467031
TI  - Metabolite profiling and identification in human urine after single oral
      administration of DEHP.
AB  - Di(2-ethylhexyl)phthalate (DEHP) is known to be a reproductive toxicant in male
      rodents, and its primary or secondary metabolites seem to be causative agents. To
      identify and quantify urinary metabolites of DEHP in humans, urine samples
      collected from healthy male and female volunteers following oral administration
      of deuterium labeled DEHP (d(4)-DEHP) at 3mg/person were analyzed by a high
      performance liquid chromatograph/mass spectrometer (LC-MS), and the excretion
      behavior of orally taken DEHP was evaluated. Mono(2-ethylhexyl)phthalate (MEHP),
      OH-MEHP, oxo-MEHP, COOH-MEHP, and their glucuronides were identified as
      metabolites in the male and female urine. The ratios of the conjugate forms in
      the total urinary metabolites were remarkably high from immediately after
      administration (0 to 4-hr post-dose), which were approximately 69% to 86% (male)
      and 80% to 89% (female) until 36-hr post-dose. It was suggested that DEHP taken
      orally was promptly converted to MEHP and its oxidative metabolites such as OH
      MEHP, oxo-MEHP, and COOH-MEHP, and most of these metabolites received the
      conjugation reaction and were excreted as glucuronides. Remarkable differences
      from rodents, in which most of these metabolites were excreted as free forms,
      were demonstrated.

PMID- 22467032
TI  - Protective effect of caffeic acid phenethyl ester against cadmium-induced renal
      damage in mice.
AB  - Cadmium (Cd) is classified as an environmental pollutant and human carcinogen.
      Caffeic acid phenethyl ester (CAPE), a biological active component of honeybee
      propolis extracts, has been used as a folk medicine with no harmful effects on
      normal cells. Here we investigated the beneficial effect of CAPE on Cd-induced
      renal damage in mice. Since renal damage induced by Cd (II) is related to
      oxidative stress, lipid peroxidation (LPO), protein carbonyl (PCO), superoxide
      dismutase (SOD), catalase (CAT) and glutathione (GSH) were evaluated. Moreover,
      the concentrations of Cd and zinc (Zn) in the kidney were analyzed. The
      intoxication of Cd (II) leads to the enhanced production of LPO and PCO, and the
      decrease of SOD activity and GSH level, probably due to the serious oxidative
      stress. However, the activities of CAT in the Cd (II)-induced group showed an
      elevated tendency, probably relating to an adaptive-response to the oxidative
      damage. The co-administration of CAPE can attenuate the oxidative stress caused
      by the intoxication of Cd and restore the altered antioxidant defense system.
      Based on our data, it is proposed that CAPE may involve in the protection of
      renal damage induced by Cd (II) owing to its antioxidant capacity and anti
      inflammatory effect.

PMID- 22467033
TI  - Differences in micronucleus induction in peripheral blood reticulocytes of mice
      exposed to N-ethyl-N-nitrosourea at light and dark dosing times.
AB  - Mammals, including human beings, have a circadian clock system to regulate
      behavioral and physiological processes. In this study, we investigated the effect
      of dosing time on micronucleus induction in the bone marrow by evaluating the
      frequencies of micronucleated peripheral reticulocytes (MNRETs) in mice exposed
      to N-ethyl-N-nitrosourea (ENU) to assess any difference in genotoxic sensitivity
      to chemicals between light and dark periods (inactive phase for rodents and
      active phase for rodents). Male C3H/He mice were treated intraperitoneally with
      ENU (12.5 or 25 mg/kg body weight) at zeitgeber time (ZT) 3 in the light period
      or ZT15 in the dark period, and then the time courses of the frequencies of the
      MNRETs were determined. The frequencies of the MNRETs induced by ENU increased
      time-dependently and peaked at 48 hr after treatment for ZT3 and ZT15, and were
      obviously higher in the ZT15 treatment group than the ZT3 treatment group. The
      MNRETs were measured at 48 hr after treatment with ENU (25 mg/kg body weight) at
      various dosing times (ZT0, 3, 6, 12, 15 and 18). The frequencies of the MNRETs in
      mice treated at ZT0, 15 and 18 were significantly higher than those in mice
      treated at ZT3, 6 and 12. These results suggest that genotoxic sensitivity to
      chemicals in mouse bone marrow is different between light and dark periods maybe
      due to different biological responses (detoxification, cell cycle, DNA repair,
      etc.) related to circadian rhythms.

PMID- 22467034
TI  - Evaluation of in vitro screening system for estrogenicity: comparison of stably
      transfected human estrogen receptor-alpha transcriptional activation (OECD TG455)
      assay and estrogen receptor (ER) binding assay.
AB  - The estrogenic activity of industrial chemicals, di(2-ethylhexyl) phthalate
      (DEHP), di(n-butyl) phthalate (DBP), benzylbutyl phthalate (BBP), diethyl
      phthalate (DEP), tetrabromobisphenol A (TBBPA), bisphenol A (BPA), and
      nonylphenol (NP), was compared using OECD test guideline 455(TG455), stably
      transfected transcriptional activation (STTA) and estrogen receptor (ER) binding
      assays. The estrogenic activity of BBP, BPA and NP were approximately 180,000
      fold (PC(50), 4.32 x 10(-6 )M),  5,000-fold (PC(50), 1.26 x 10(-7) M) and 120,000
      fold (PC(50), 2.92 x 10(-6 )M) less than 17beta-estradiol (PC(50), 2.43 x 10(
      11)M), whereas DEHP, DBP and DEP did not show any estrogenicity activity in the
      STTA assay. Moreover, binding affinities to human ERalpha of BBP, BPA, and NP
      were approximately 200,000-fold (IC(50), 4.91 x 10(-4) M), 8000-fold (IC(50),
      1.92 x 10(-5) M) and 1400-fold (IC(50), 3.34 x 10(-6) M) less than 17beta
      estradiol (IC(50), 2.45 x 10(-9) M) in competitive human ERalpha binding assay.
      The relative potencies of STTA assay were very similar to ER binding, E-screen,
      and Yeast screening assays. Therefore, our results suggested that OECD test
      guideline TG455 may be useful as a screening test for potential endocrine
      disruptors.

PMID- 22467036
TI  - Macrophage depletion ameliorates kavalactone damage in the isolated perfused rat
      liver.
AB  - Liver toxicity is a side effect observed with some herbal treatments, including
      Piper methysticum. The possible mechanisms responsible include inflammation
      subsequent to activation of liver macrophages and oxidative damage.
      Hepatotoxicity of the pharmacologically active component of Piper methysticum
      (kavalactones) was tested in isolated, perfused livers from rats which were
      pretreated with the macrophage intoxicant gadolinium chloride. Perfusions without
      kavalactones in gadolinium chloride pretreated and untreated livers were included
      as negative controls. Serial liver lobe biopsies were collected to measure
      temporal changes in available (reduced) hepatic glutathione. There were no
      statistically significant changes in reduced glutathione over the course of
      perfusion in any experimental group. Liver damage was observed using electron
      microscopy. Hepatic sinusoids displayed extensive damage to the endothelium in
      kavalactone-perfused, rat livers. This damage was significantly reduced by pre
      treatment with gadolinium chloride. Hence liver macrophages may be a factor in
      liver injury induced by Piper methysticum. Characterisation and modulation of the
      liver macrophage response may enable the development of strategies to avoid these
      hepatic side effects.

PMID- 22467035
TI  - Enhancing effects of trichloroethylene and tetrachloroethylene on type I allergic
      responses in mice.
AB  - Trichloroethylene (TCE) and tetrachloroethylene (perchloroethylene; PCE) are
      commonly identified as environmental contaminants of groundwater. Previously, we
      investigated the enhancing effects of TCE and PCE on antigen-induced histamine
      release and inflammatory mediator production in rat mast cells. In this study, to
      examine the potential effect of TCE and PCE on antigen-induced histamine release
      from mouse mast cells, mouse bone marrow-derived mast cells (BMMC) were
      sensitized with anti-dinitrophenol (DNP) monoclonal IgE antibody and then
      stimulated with DNP-BSA containing with TCE or PCE. Both TCE and PCE
      significantly enhanced antigen-induced histamine release from BMMC. Next we
      investigated the effects of TCE and PCE on the passive cutaneous anaphylaxis
      (PCA) reaction in vivo using ICR mice. TCE and PCE significantly enhanced the PCA
      reaction in a dose-dependent manner. In addition, we examined the enhancing
      effects of ingesting small amount of TCE and PCE in drinking water on antigen
      stimulated allergic responses. After the ICR mice had ingested TCE or PCE in
      their drinking water for 2 or 4 weeks, we performed the PCA reaction. Both TCE
      and PCE ingestion enhanced the PCA reaction in a dose-dependent manner for 4
      weeks. These results suggest that exposure to TCE and PCE leads to the
      augmentation of type I allergic responses in many species.

PMID- 22467037
TI  - Changes of Treg-associated molecules on CD4+CD25 +Treg cells in myasthenia gravis
      and effects of immunosuppressants.
AB  - OBJECTIVE: Myasthenia gravis (MG) is a CD4(+) T cell-dependent autoimmune
      disease, and close attention has been paid to the role of CD4(+)CD25(+)Treg cells
      (Tregs). Previous results regarding Tregs in MG patients have been conflicting.
      The discrepancy was partly ascribed to selecting different Treg-associated
      molecules in defining Tregs. Therefore, we considered it necessary to find a
      reliable index for assessing the immunologic state in MG patients and explore the
      effect of IS on them. METHODS: We adopted flow cytometric techniques to measure
      the numbers and frequencies of Tregs in peripheral blood taken from 57 patients
      and 91 age-matched healthy donors, and we also analyzed FOXP3 mean fluorescence
      intensity on Tregs. RESULTS: The number and frequency of Tregs in peripheral
      blood of MG patients significantly decreased, together with down-regulation of
      FOXP3 expression. There was dynamic change of Treg cell level and the inverse
      relationship with clinical symptom, suggesting that the immunologic disorder in
      MG patients was related to peripheral Tregs population. Meanwhile,
      CD4(+)CD25(+)FOXP3(+)Helios(+)T cells might be activated Tregs, rather than
      nTregs. Moreover, the number and frequency of CD4(+)CD25(+)FOXP3(+)Helios(+)T
      cells significantly decreased in MG patients, indicating that the reduction of
      the activated Tregs population might be a critical contributor to the
      pathogenesis of MG. CONCLUSIONS: The significant reduction of the peripheral
      Tregs population in MG patients might be responsible for the immunologic
      disorders in MG patients. IS such as GC took its effect possible by increasing
      the population size, and the underlying mechanism should be further investigated.

PMID- 22467038
TI  - Neuronal images of the putamen in the adult human neostriatum: a revised
      classification supported by a qualitative and quantitative analysis.
AB  - A qualitative analysis of the morphology of human putamen nerve cells involves a
      detailed description of the structure and features of neurons and, accordingly,
      their classification into already defined classes and types. In our sample of 301
      neurons, 64.78 % (195) were spiny and 35.22 % (106) aspiny cells. By analyzing
      cell bodies and dendritic trees, we subdivided spiny cells into two types (I and
      II) and aspiny cells into three types (III, IV and V). Our sample of neurons,
      classified according to the previously described scheme, consisted of 80 type I,
      115 type II, 16 type III, 42 type IV and 48 type V nerve cells. In the present
      study, after qualitative analysis of microscopic images of the Golgi impregnated
      neurons of the putamen, we measured/quantified five morphological properties,
      i.e., the sizes of the soma and dendritic field, shape of the neuron,
      straightness of individual dendrites and the branching complexity of the
      dendritic tree, using eight morphometric parameters. Hence, we identify five
      types of nerve cells in the human putamen: type I-small spiny neurons; type II
      large spiny neurons; type III-large aspiny neurons; type IV-neurons with a large
      soma and a medium dendritic field; and type V-small aspiny neurons. By performing
      an adequate statistical analysis on these parameters, we point out that the
      proposed types differ enough in their morphology to warrant our qualitative
      classification.

PMID- 22467039
TI  - Gene expression analysis to identify molecular correlates of pre- and post
      conditioning derived neuroprotection.
AB  - Mild ischaemic exposures before or after severe injurious ischaemia that elicit
      neuroprotective responses are referred to as preconditioning and post
      conditioning. The corresponding molecular mechanisms of neuroprotection are not
      completely understood. Identification of the genes and associated pathways of
      corresponding neuroprotection would provide insight into neuronal survival,
      potential therapeutic approaches and assessments of therapies for stroke. The
      objectives of this study were to use global gene expression approach to infer the
      molecular mechanisms in pre- and post-conditioning-derived neuroprotection in
      cortical neurons following oxygen and glucose deprivation (OGD) in vitro and then
      to apply these findings to predict corresponding functional pathways. To this
      end, microarray analysis was applied to rat cortical neurons with or without the
      pre- and post-conditioning treatments at 3-h post-reperfusion, and differentially
      expressed transcripts were subjected to statistical, hierarchical clustering and
      pathway analyses. The expression patterns of 3,431 genes altered under all
      conditions of ischaemia (with and without pre- or post-conditioning). We
      identified 1,595 genes that were commonly regulated within both the pre- and post
      conditioning treatments. Cluster analysis revealed that transcription profiles
      clustered tightly within controls, non-conditioned OGD and neuroprotected groups.
      Two clusters defining neuroprotective conditions associated with up- and
      downregulated genes were evident. The five most upregulated genes within the
      neuroprotective clusters were Tagln, Nes, Ptrf, Vim and Adamts9, and the five
      most downregulated genes were Slc7a3, Bex1, Brunol4, Nrxn3 and Cpne4. Pathway
      analysis revealed that the intracellular and second messenger signalling pathways
      in addition to cell death were predominantly associated with downregulated pre-
      and post-conditioning associated genes, suggesting that modulation of cell death
      and signal transduction pathways plays a role in the neuroprotection. A high
      degree of similarity in the pathways associated with the differentially expressed
      genes in the pre- and post-conditioning treatments suggests that similar
      molecular mechanisms may mediate their neuroprotective effects.

PMID- 22467041
TI  - Effect of roughage to concentrate ratio of sweet sorghum (Sorghum biclor L.
      Moench) bagasse-based complete diet on nutrient utilization and microbial N
      supply in lambs.
AB  - An experiment was conducted to study the effect of roughage to the concentrate
      ratio of complete diets containing sweet sorghum bagasse (SSB), an agro
      industrial by product, as sole roughage source on nutrient utilization in ram
      lambs. Twenty-four Nellore * Deccani cross ram lambs aged about 3 months (average
      body wt. 10.62 +/- 0.03 kg) were randomly allotted into four groups fed with CR-I
      (60R:40C), CR-II (50R:50C), CR-III (40R:60C), and CR-IV (30R:70C) complete diets.
      The roughage to concentrate ratio did not affect the dry matter intake (in
      grams/day or grams/kilogram weight(0.75)). The crude protein (P < 0.01) and ether
      extract (P < 0.05) digestibility of ration CR-IV was higher than CR-I and CR-II
      rations, whereas, the digestibility of nitrogen-free extract and fiber fractions
      was similar among all the rations. Experimental diets were different (P < 0.01)
      in digestible crude protein (DCP) content, in which the CR-I ration contained
      lower DCP value whereas CR-IV ration contained higher DCP value. The total
      digestible nutrients (TDN) and metabolizable energy (ME) values were comparable
      among all the experimental rations. The daily DCP intake (in grams/day) was lower
      (P < 0.05) in lambs fed with CR-I ration compared to CR-III and CR-IV rations and
      it was comparable with CR-II ration. The TDN intake (in grams/day), digestible
      energy, and ME intakes (in megajoules/day) were similar among the lambs fed
      experimental rations with different SSB to concentrate ratios. The average daily
      DCP intake of lambs fed with CR-II, CR-III, and CR-IV rations met the
      requirements whereas, the daily TDN and ME intake was met by all the lambs. The
      lambs on all the diets were in positive nitrogen retention. The nitrogen balance
      expressed as grams/day was higher (P < 0.05) in lambs fed with CR-III and CR-IV
      ration than those fed with CR-I ration. The daily calcium and phosphorus intake
      and balance were comparable on all the experimental rations. The total purine
      derivatives (in millimoles/day) were higher (P < 0.05) in CR-III than CR-I and
      comparable with CR-II and CR-IV diets. The higher (P < 0.01) microbial N supply
      (in grams/day) was observed in CR-III ration compared to other three rations and
      the efficiency of microbial synthesis was comparable among all the rations. It is
      concluded that sweet sorghum bagasse can be included in the complete rations at
      maximum level of 50 % as roughage source for rearing of ram lambs.

PMID- 22467040
TI  - Influence of cholesterol on cellular signaling and fusion pore kinetics.
AB  - Cholesterol is an important lipid component of cellular membranes. Recent studies
      have shown that changes in cellular cholesterol level can affect cellular
      functions. Here, we summarize our recent findings on the impact of cholesterol on
      the glucose-stimulated Ca(2+) signaling in rat pancreatic beta cells and the
      fusion pore kinetics of large dense core granules in rat chromaffin cells. In
      mouse pancreatic beta cells, pharmacological elevation of cellular cholesterol
      (but not cholesterol extraction) reduced the current density of the delayed
      rectifier K(+) channels, the ATP-dependent K(+) channels, and voltage-gated
      Ca(2+) channels. Importantly, cholesterol enrichment impaired glucose-stimulated
      Ca(2+) signaling in mouse pancreatic beta cells via a suppression of voltage
      gated Ca(2+) channels and a decrease in mitochondrial ATP production, which in
      turn led to a reduction in the glucose-evoked depolarization. In rat chromaffin
      cells, we found that the persistence of the semi-stable fusion pore was increased
      by cholesterol enrichment, and acute cholesterol extraction from the cytosolic
      side of the cell destabilized the semi-stable fusion pore. Overall, our findings
      highlight the importance of cholesterol in the regulation of cellular signaling
      and exocytosis.

PMID- 22467042
TI  - Impact of tsetse and trypanosomiasis control on cattle herd composition and calf
      growth and mortality at Arbaminch District (Southern Rift Valley, Ethiopia).
AB  - The effect of tsetse/trypanosomiasis control on cattle herd composition and
      growth and mortality of calves in tsetse controlled (by Southern Tsetse
      Eradication Project (STEP)) and uncontrolled blocks in southern Ethiopia was
      assessed. Structured questionnaire was used to interview 182 households to
      estimate cattle herd composition and calf mortality. Calves were bled to examine
      the presence of trypanosomes by the buffy coat technique. Forty NGU traps were
      deployed and fly catches determined. A case-control study was performed on 40
      calves for 6 months to estimate calve growth parameters. Accordingly, the mean
      cattle herd size was lower in tsetse-controlled block than in the uncontrolled
      block, whereas the relative number of calves in a herd tend to be higher in the
      tsetse-controlled block (P = 0.06). While there was no report of cattle mortality
      in tsetse-controlled block, 16.48 % of the respondents have lost calves in tsetse
      uncontrolled block in 1 year time. The prevalence of trypanosome positive calves
      was 2.95 % for uncontrolled block but no positive case in tsetse-controlled
      block. The apparent densities of flies/trap/day in tsetse-uncontrolled block were
      30-fold higher than in tsetse-controlled block (P < 0.01). The case-control study
      revealed that the mean body weight gain of calves in tsetse-controlled block
      (40.23 +/- 0.7 kg) was significantly higher than that of the uncontrolled block
      (34.74 +/- 0.68 kg). The above findings strongly suggest that the intervention by
      the STEP project has significantly reduced tsetse population and trypanosomiasis
      consequently contributing to improved calf growth and survival.

PMID- 22467043
TI  - Estimating pasture intake and nutrient digestibility of growing pigs fed a
      concentrate-forage diet by n-alkane and acid-insoluble ash markers.
AB  - A study was carried out to determine voluntary forage intake and nutrient
      digestibility in growing pigs fed a mixed forage and concentrate diet. Twenty
      five 8-week-old Large White * Landrace crossbred male pigs (27 +/- 3.8 kg) were
      blocked by weight into five groups, and each was randomly allocated to four
      indoor treatments (A, B, C, and D), which received 100, 90, 80, and 70 % of ad
      lib concentrated intake and an outdoor treatment (E) that received 80 % of ad lib
      concentrate. Indoor treatments were either fed the concentrate only (A) or also
      received freshly cut Kikuyu grass (Pennissetum clandestinum) ad libitum (B, C,
      and D), while pigs on treatment E were reared outdoors in Kikuyu grass paddocks.
      There was a significant correlation between the amount of concentrate offered and
      its intake (P < 0.01). The intake of Kikuyu was similar among treatments (P >
      0.05). Mean acid-insoluble ash digestibility estimates of organic and dry matter
      were superior to C(32) estimates (P < 0.05). Kikuyu intake was higher (P < 0.05)
      than the estimated intake by 0.076 +/- 0.03 kg. It was concluded that Kikuyu
      intake was not affected by the reduction of the concentrate allowance, and this
      should be taken into consideration when feeding pigs on pasture.

PMID- 22467044
TI  - Calcium orthophosphate-based bone cements (CPCs): Applications, antibiotic
      release and alternatives to antibiotics.
AB  - Calcium orthophosphate bone cements (CPCs) are widely used in orthopedic surgery.
      Implants are highly susceptible to infection and often lead to the formation of
      microbial biofilms. Antibiotics are often incorporated into bone cement to
      prevent infection. The increase in the number of microorganisms acquiring or
      developing resistance to antibiotics, such as methicillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), is a
      major concern. Bacteriocins (antimicrobial peptides) offer an alternative to
      antibiotics. Their mode of activity involves permanent destabilization of the
      plasma membrane of target cells. A number of broad-spectrum bacteriocins produced
      by lactic acid bacteria and Bacillus spp. have recently been reported. In this
      REVIEW the major characteristics of calcium phosphate bone cements, prosthetic
      joint-associated infections, and treatment of these infections is discussed. The
      role of antimicrobial agents in CPCs is discussed and the possibility of
      incorporating bacteriocins in prosthetic devices is investigated.

PMID- 22467048
TI  - Analysis of tantalum implants used for avascular necrosis of the femoral head: a
      review of five retrieved specimens.
AB  - AIM: The effective results shown in the porous systems of tantalum employed for
      the use of osseointegrates has been demonstrated by means of animal
      experimentation. However, there is a total lack of any research studies on the
      osseointegration of tantalum implants from retrieval of the same after a period
      of time whereby the material had been implanted within the human body. MATERIALS
      AND METHODS: For this study, five rod implants used for the treatment of
      avascular necrosis of the femoral head were retrieved following collapse of the
      femoral head and conversion to total hip arthroplasty. The time of implantation
      ranged between six weeks and twenty months. RESULTS: Observation during this
      study has confirmed the effectiveness of osseointegration within this period of
      time. New bone was observed around and within the porous system of the on rod
      devices at retrieval date. The bone ingrowth, however, proved to be slower and
      less intense than that resulting within animal species during the first few
      months after implantation. CONCLUSIONS: Nevertheless, the results obtained in the
      quantitative assessment of this process proved to be similar to those results
      achieved by other authors in previous experimental work studies.

PMID- 22467049
TI  - Apatite formation on nanomaterial calcium phosphate/poly-DL-lactide-co-glycolide
      in simulated body fluid.
AB  - Simulated body fluid (SBF) is an artificial fluid which has ionic composition and
      ionic concentration similar to human blood plasma. PURPOSE: This paper compares
      the interaction between the nanomaterial containing calcium phosphate/poly-dl
      lactide-co-glycolide (N-CP/PLGA) and SBF, in order to investigate whether and to
      what extent inorganic ionic composition of human blood plasma leads to the
      aforementioned changes in the material. METHODS: N-CP/PLGA was incubated for 1,
      2, 3, and 5 weeks in SBF. The surface of the material was analyzed on SEM-EDS and
      FTIR spectrometer, while SBF was subjected to pH and electrical conductivity
      measurement. RESULTS: Our results indicate that dissolution of the polymer
      component of the material N-CP/PLGA and precipitation of the material similar to
      hydroxyapatite on its surface are based on the morphologic changes seen in this
      material. CONCLUSIONS: The mechanism of the apatite formation on the bioceramic
      surface was intensively studied and was considered crucial in designing the new
      biomaterials. The results obtained in this work indicate that N-CP/PLGA may be a
      good candidate for application to bone regeneration.

PMID- 22467051
TI  - Spinal anesthesia in pediatric patients.

PMID- 22467050
TI  - Chronic pain: not only a matter of time.
AB  - The term "chronic" is often used in daily clinical practice to indicate a type of
      pain that lasts over time and is accompanied by diagnostic and therapeutic
      difficulties. The common feeling is that in this category are actually collected
      many different clinical cases with the unique characteristic that the pain lasts
      a long time. It follows that treatment failures are common and patients roam from
      doctor to doctor in search of an effective care program. At the same time the
      health spending for the treatment of these patients is becoming increasingly
      high. In clinical practice we meet many patients with obscure pain syndromes
      which are classified as "chronic" and untreatable only because persist for long
      time and that obtain a complete pain relief after a right diagnosis and a
      specific treatment. In this review the Authors want to argue that the term
      chronic should not be used only when the pain persists for some time or just when
      signs and symptoms of mechanisms in the central nervous systems are present. The
      authors suggest that there is a clear difference between acute and chronic pain
      but also that in chronic pain patients there are three different painful
      conditions: 1) patients with a chronic disease (or sequelae) and with chronic
      pain in which the pain mechanisms are closely related to the underlying chronic
      disease (e.g., rheumatoid arthritis) or to previous injury that has generated
      other unsolvable mechanisms (e.g., deafferentation pain after plexus avulsion);
      2) patients with a chronic disease and chronic pain in which new mechanisms
      overlap those related to the underlying disease; 3) patients with chronic pain in
      whom the correlation between pain and the initial tissue injury is lost and the
      persistence of pain is due to new developed mechanisms. According to this
      classification we can distinguish patients with "painful chronic disease" by
      patients with "independent chronic pain". In these latter cases the complexity of
      the clinical picture is to be found in a maladaptative response to pain, in
      emergence of central nervous system mechanisms and in behavioral changes that, in
      turn, can cause long-term social, psychological and physical sequelae.
      Differences among patients in developing chronic pain can be related to
      differences in the ability of the brain to continuously adapt its functional and
      structural organization. It is obvious that the care plan for these complex
      patients is profoundly different from that needed for patients with pain linked
      to a chronic disease or stabilized pain mechanisms. The purpose of the present
      article is to provide a review of the most noteworthy developments in this field
      and to propose some observations that may help to understand this pain condition
      and the patients.

PMID- 22467052
TI  - Should we really consider to lay down the Macintosh laryngoscope?

PMID- 22467053
TI  - Functional importance of laparoscopic sleeve gastrectomy for the lower esophageal
      sphincter in patients with morbid obesity.

PMID- 22467054
TI  - Gold nanoparticles functionalised with stable, fast water exchanging Gd3+
      chelates as high relaxivity contrast agents for MRI.
AB  - Gold nanoparticles functionalized with Gd(3+) chelates displaying fast water
      exchange, superb pH stability and inertness towards transmetalation with Zn(2+)
      have been prepared and characterized as a new high relaxivity (29 mM(-1) s(-1),
      30 MHz, 25  degrees C) contrast agent potentially safe for in vivo MRI
      applications. The Lipari-Szabo treatment for internal rotation was used to
      evaluate the effect of linker flexibility on the relaxivity of the gold
      nanoparticles. The effect of fast water exchange on the relaxivity of gold
      nanoparticles functionalized with Gd(3+) chelates is also addressed in this
      communication.

PMID- 22467056
TI  - Interview with Paul Beer.

PMID- 22467057
TI  - Niacin improves ischemia-induced neovascularization in diabetic mice by
      enhancement of endothelial progenitor cell functions independent of changes in
      plasma lipids.
AB  - Niacin was shown to inhibit acute vascular inflammation and improves endothelial
      dysfunction independent of changes in plasma lipids. Here, we investigated
      whether niacin can increase blood flow recovery after tissue ischemia by
      enhancing endothelial progenitor cell (EPC) functions in diabetic mice. Starting
      at 4 weeks after the onset of diabetes, vehicle or niacin (40 mg/kg/day) was
      administered daily by gavage to streptozotocin (STZ)-induced diabetic mice and
      diabetic endothelial nitric oxide synthase (eNOS)-deficient mice. Unilateral
      hindlimb ischemia surgery was conducted after 2 weeks of vehicle or niacin
      treatment. Compared to the control group, the niacin group had significantly
      increased ischemic/non-ischemic limb blood perfusion ratio and higher capillary
      density. These effects were markedly reduced in STZ-induced diabetic eNOS
      deficient mice. Flow cytometry analysis showed impaired EPC-like cell (Sca
      1(+)/Flk-1(+)) mobilization after ischemia surgery in diabetic mice but augmented
      mobilization in the mice treated with niacin. Diabetes was induced by
      administering STZ to FVB mice that received eGFP mouse bone marrow cells to
      evaluate effects of niacin on bone marrow-derived EPC homing and differentiation
      to endothelial cells. Differentiation of bone marrow-derived EPCs to endothelial
      cells in the ischemic tissue around vessels in diabetic mice that received niacin
      treatment, was significantly increased than that in control group. By in vitro
      studies, incubation with niacin in high-glucose medium reduced H(2)O(2)
      production, cell apoptosis, and improved high glucose-suppressed EPC functions by
      nitric oxide-related mechanisms. Our findings demonstrate that niacin increases
      blood flow recovery after tissue ischemia in diabetic mice through enhancing EPC
      mobilization and functions via nitric oxide-related pathways.

PMID- 22467055
TI  - Advanced glycation end products (AGE) induce the receptor for AGE in the colonic
      mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid
      and high-glucose diet.
AB  - BACKGROUND: Advanced glycation end products (AGE) and the receptor for advanced
      glycation end products (RAGE) are closely associated with colorectal cancer
      progression. The association between RAGE and AGE in colon carcinogenesis needs
      to be clarified. METHODS: Levels of RAGE and AGE were examined in azoxymethane
      (AOM)-injected Fischer 344 rats fed a control diet (Group C), a 15 % linoleic
      acid (LA) diet (Group L), a control diet with 10 % glucose drink (Group G), and a
      15 % LA diet with 10 % glucose drink (Group L + G). Group L + G showed the most
      pronounced increase of body weight, blood sugar, and serum insulin. RESULTS: The
      rats in Group L + G showed the most pronounced multiplicity of aberrant crypt
      foci (ACF) and carcinomas with increased mucosal RAGE and AGE. IEC6 rat
      intestinal epithelial cells treated with AGE showed increased RAGE expression,
      which was inhibited by treatment with metformin or losartan. In the AOM-injected
      rat colon cancer model, the levels of RAGE and AGE, and the multiplicity of ACF
      and carcinomas, in Group L + G rats were suppressed by treatment with metformin
      or losartan. CONCLUSIONS: These results suggest that AGE-RAGE induced by high-LA
      and high-glucose diets substantially enhances colon cancer development; thus,
      suppression of AGE-RAGE could be a potential target for colon cancer
      chemoprevention.

PMID- 22467058
TI  - History of fuel consumption inferred from polycyclic aromatic hydrocarbons in
      sediments from the south Lianhuan Lake, northeast China.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic
      pollutants of global concern. The current study uses differences in PAH profiles
      in 1 cm core sediment samples from south Lianhuan Lake, Heilongjiang Province,
      China to evaluate historical changes in fuel sources. Individual core segments
      were dated using (137)Cs techniques and concentrations of 16 priority PAHs were
      measured. Principal components analysis with multivariate linear regression and
      PAH profiles of specific combustion sources were used to identify historical fuel
      use. During the early 1940s to the early 1970s, PAHs concentrations increases
      with the increased combustion of coal, and relatively high petroleum source could
      be linked to the establishment of the Daqing Oil Field. The source apportionment
      suggested that coal combustion replaced wood burning and became the dominant fuel
      since the 1940s and petroleum source increased. These results were coincidence
      with the rapid economic growth occurring in China.

PMID- 22467059
TI  - Analysis of individual versus group behavior of zebrafish: a model using pH
      sublethal effects.
AB  - An image analysis biomonitoring system was used to evaluate sublethal effects of
      pH on the mean swimming velocity of zebrafish. Responses to stress were tested
      comparing individual and group responses. Group analysis indicated no effect for
      all acid pH and for pH 9.0-9.5. Individual analysis indicated behavioral
      differences for most acid pH and higher than 9.5. Sensitivity to sublethal pH was
      best assessed when using individual analysis. Zebrafish decreased hyperactivity
      and increased hypoactivity with more acid or alkaline pH. Individual approach
      allowed to determine hyperactivity or hypoactivity and the species' thresholds of
      exposure, which is critical for the management of impairments.

PMID- 22467060
TI  - Small hepatocellular carcinomas: ultrasonography guided percutaneous
      radiofrequency ablation.
AB  - Current guidelines advocate percutaneous radiofrequency (RF) ablation as a
      standard treatment of early stage hepatocellular carcinoma (HCC) for up to three
      tumors <=3 cm in diameter. The local efficacy evaluated with short-term
      radiological examination may be overrated, whereas that assessed by
      histopathological measure might be underestimated. Long-term clinical follow-up
      studies guarantee the effectiveness of RF ablation for small HCC, which is now
      almost comparable in benefits to surgical resection. US is the most common
      guiding modality for percutaneous RF ablation for small HCC. However, the
      technical feasibility is often limited due to poor conspicuity of the index tumor
      on US. Implementation of artificial ascites, contrast-enhanced harmonic US, and
      fusion imaging of US with CT/MR can be helpful to enhance the technical
      feasibility of US-guided RF ablation of small HCC.

PMID- 22467061
TI  - Neoadjuvant or adjuvant therapy for resectable gastric cancer: a systematic
      review and practice guideline for North America.
AB  - BACKGROUND: Gastric cancer is a global health problem accounting for 10% of all
      new cancer cases and 12% of all cancer deaths worldwide. Many clinical trials and
      meta-analyses have explored the value of neoadjuvant or adjuvant chemotherapy and
      radiation therapy in gastric cancer; however, these studies have produced
      conflicting results. The purpose of this guidance document was to determine
      whether patients with resectable gastric cancer should receive neoadjuvant or
      adjuvant therapy in addition to surgery. Outcomes of interest were overall
      survival, disease-free survival, and adverse events. METHODS: A systematic review
      was undertaken to inform recommendations regarding neoadjuvant and adjuvant
      therapy in resectable gastric cancer in Ontario, Canada. MEDLINE and EMBASE
      databases, as well as American Society of Clinical Oncology (ASCO) annual meeting
      proceedings and American Society for Therapeutic Radiology and Oncology (ASTRO)
      proceedings were systematically searched from 2002 to 2010. Oral fluoropyrimidine
      trials were excluded owing to the unavailability of these agents in North
      America. RESULTS: Overall, 22 randomized controlled trials (RCTs), 13 meta
      analyses, and two secondary analyses were included. The systematic review
      informed the development of a clinical practice guideline with the following
      recommendations. Postoperative 5-fluorouracil-based chemoradiotherapy based on
      the Macdonald approach or perioperative ECF (epirubicin, cisplatin, fluorouracil)
      chemotherapy based on the Cunningham/MAGIC (Medical Research Council Adjuvant
      Gastric Infusional Chemotherapy) approach are both acceptable standards of care
      in North America. Choice of treatment should be made on a case-by-case basis.
      Adjuvant chemotherapy is a reasonable option for those patients for whom the
      Macdonald and MAGIC protocols are contraindicated. All patients with resectable
      gastric cancer should undergo a pretreatment multidisciplinary assessment to
      determine the best plan of care. CONCLUSIONS: Overall survival in patients with
      resectable gastric cancer is significantly improved with the use of either
      postoperative chemoradiation (Macdonald approach) or perioperative ECF (MAGIC
      protocol).

PMID- 22467062
TI  - Long-term outcomes of Roux-en-Y and Billroth-I reconstruction after laparoscopic
      distal gastrectomy.
AB  - BACKGROUND: Laparoscopic distal gastrectomy (LDG) is an established procedure for
      the treatment of early gastric cancer. Roux-en-Y (R-Y) or Billroth-I (B-I)
      reconstruction is generally performed after LDG in Japan. The aim of this
      retrospective cohort study was to compare the effectiveness of R-Y and B-I
      reconstructions and thereby determine which has better clinical outcomes.
      METHODS: We analyzed data from 172 patients with gastric cancer who underwent
      LDG. Reconstruction was done by R-Y in 83 patients and B-I in 89. All patients
      were followed up for 5 years. Evaluated variables included symptoms, nutritional
      status, endoscopic findings, gallstone formation, and later gastrointestinal
      complications. RESULTS: Scores for the amount of residue in the gastric stump,
      remnant gastritis, and bile reflux, calculated according to the "residue,
      gastritis, bile" scoring system, were significantly lower in the R-Y group (score
      0 vs. 1 and more; p = 0.027, <0.001, and <0.001, respectively). The proportion of
      patients with reflux esophagitis was significantly lower in the R-Y group (p <
      0.001). Relative values (postoperative 5 years/preoperative) for body weight,
      serum albumin level, and total cholesterol level were similar in the two groups
      (p = 0.59, 0.56, and 0.34, respectively). Gallstone formation did not differ
      between the groups (p = 0.57). As for later complications, the incidence of
      gastrointestinal ulcer was 4.5 % in the B-I group, and that of ileus was 3.6 % in
      the R-Y group, but differences between the groups were not significant (p = 0.12,
      0.11, respectively). CONCLUSIONS: As compared with B-I, R-Y was associated with
      lower long-term incidences of both bile reflux into the gastric remnant and
      reflux esophagitis.

PMID- 22467063
TI  - Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with
      autism.
AB  - Autism is a neurodevelopmental disorder characterized by deficits in social
      interaction and social communication, as well as by the presence of repetitive
      and stereotyped behaviors and interests. Brodmann areas 44 and 45 in the inferior
      frontal cortex, which are involved in language processing, imitation function,
      and sociality processing networks, have been implicated in this complex disorder.
      Using a stereologic approach, this study aims to explore the presence of
      neuropathological differences in areas 44 and 45 in patients with autism compared
      to age- and hemisphere-matched controls. Based on previous evidence in the
      fusiform gyrus, we expected to find a decrease in the number and size of
      pyramidal neurons as well as an increase in volume of layers III, V, and VI in
      patients with autism. We observed significantly smaller pyramidal neurons in
      patients with autism compared to controls, although there was no difference in
      pyramidal neuron numbers or layer volumes. The reduced pyramidal neuron size
      suggests that a certain degree of dysfunction of areas 44 and 45 plays a role in
      the pathology of autism. Our results also support previous studies that have
      shown specific cellular neuropathology in autism with regionally specific
      reduction in neuron size, and provide further evidence for the possible
      involvement of the mirror neuron system, as well as impairment of neuronal
      networks relevant to communication and social behaviors, in this disorder.

PMID- 22467064
TI  - Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background
      and current applications.
AB  - Conventional cardiovascular monitoring may not detect tissue hypoxia, and
      conventional cardiovascular support aiming at global hemodynamics may not restore
      tissue oxygenation. NIRS offers non-invasive online monitoring of tissue
      oxygenation in a wide range of clinical scenarios. NIRS monitoring is commonly
      used to measure cerebral oxygenation (rSO(2)), e.g. during cardiac surgery. In
      this review, we will show that tissue hypoxia occurs frequently in the
      perioperative setting, particularly in cardiac surgery. Therefore, measuring and
      obtaining adequate tissue oxygenation may prevent (postoperative) complications
      and may thus be cost-effective. NIRS monitoring may also be used to detect tissue
      hypoxia in (prehospital) emergency settings, where it has prognostic significance
      and enables monitoring of therapeutic interventions, particularly in patients
      with trauma. However, optimal therapeutic agents and strategies for augmenting
      tissue oxygenation have yet to be determined.

PMID- 22467065
TI  - Suggestions from the field for return to sports participation following anterior
      cruciate ligament reconstruction: soccer.
AB  - Successful return to play remains a challenge for a soccer player after anterior
      cruciate ligament reconstruction. In addition to a successful surgical
      intervention, a soccer-specific functional rehabilitation program is essential to
      achieve this goal. Soccer-like elements should be incorporated in the early
      stages of rehabilitation to provide neuromuscular training specific to the needs
      of the player. Gym-based and, later, field-based drills are gradually intensified
      and progressed until the player demonstrates the ability to return to team
      practice. In addition to the recovery of basic attributes such as mobility,
      flexibility, strength, and agility, the surgically repaired knee must also regain
      soccer-specific neuromuscular control and conditioning for an effective return to
      sports. The individual coaching of the player by the sports physiotherapist and
      compliance with the training program by the player are key factors in the
      rehabilitation process. To minimize reinjury risk and to maximize the player's
      career, concepts of soccer-specific injury prevention programs should be
      incorporated into the training routine during and after the rehabilitation of
      players post-ACL reconstruction.

PMID- 22467066
TI  - Influences observed on incidence and reporting of medication errors in
      anesthesia.
AB  - BACKGROUND: Medication errors are a common occurrence during the conduct of
      anesthesia (one in 133-450 [corrected] patients). Several factors contribute to
      medication errors in anesthesia, including experience of the anesthesia provider,
      severity of comorbidities, and type of procedure. The inexperience of anesthesia
      providers-in-training also leads to increased error rates. This prospective
      observational study repeats and extends previous work by Webster et al. and
      Llewellyn et al. examining the role of comorbidities, type of case, and level of
      provider experience on the incidence of medication errors. METHODS: After
      Institutional Review Board review and exemption from informed consent, medication
      error reporting forms were attached to every anesthetic record during a six-month
      period. All providers were asked to return the forms for every anesthetic, on a
      strictly voluntary and anonymous basis, and to record the occurrence of
      medication errors. If providers indicated that a medication error had occurred,
      additional details about the event were obtained anonymously. RESULTS: There were
      8,777 (83%) responses obtained in a review of 10,574 case forms. A medication
      error was reported in 35 forms, with an additional 17 forms indicating a
      medication pre-error or near miss, resulting in 52 (0.49%) errors/pre-errors or a
      reported incidence of 1:203 anesthetics. Most case types were observed to have a
      statistically significant increase in reported medication errors. Reported errors
      by type of anesthesia provider were categorized into anesthesia provider-in
      training group and the experienced provider group. The anesthesia provider-in
      training group reported a twofold increase in the rate of errors, with the most
      frequently reported errors being incorrect dose and substitution. CONCLUSION:
      This study suggests that case type, American Society of Anesthesiologists'
      classification, and level of provider experience play a role on the rate of
      medication errors. The results of this study are in agreement with previously
      reported error rates.

PMID- 22467067
TI  - Cardiac arrest in the operating room requiring prolonged resuscitation.
AB  - PURPOSE: Prolonged cardiopulmonary resuscitation (CPR) is often associated with
      limited success and poor long-term outcomes. The purpose of this report is to
      present the case of a patient who suffered an unanticipated cardiac arrest in the
      operating room and survived following a prolonged period of CPR. CLINICAL
      FEATURES: A previously healthy 53-yr-old male with inflammatory bowel disease was
      diagnosed with a perforated bowel and underwent emergency exploratory laparotomy
      under general anesthesia. Approximately two hours after induction of anesthesia,
      the patient experienced cardiac arrest, and for 55 min, he underwent CPR and
      defibrillation according to the Advanced Cardiac Life Support (ACLS) protocols.
      As the decision to terminate CPR was being considered, a return of spontaneous
      circulation was detected 56 min after the onset of cardiac arrest. The patient
      survived with no major organ failure or adverse neurological outcome. No
      definitive cause of cardiac arrest was diagnosed in the postoperative period. At
      the follow-up 14 months after the event, the patient had returned to the pre
      arrest level of functioning. The results of our literature search showed that no
      upper limit for the duration of CPR has been defined. Good outcomes after
      prolonged CPR depend on the patient's pre-arrest condition and the etiology of
      the cardiac arrest. CONCLUSION: Perioperative cardiac arrests are rare events,
      and there is little evidence to suggest an upper limit for the duration of
      resuscitation. Unknown etiologies and the presence of good patient predictors may
      support the continuation of prolonged CPR with good outcomes.

PMID- 22467068
TI  - Anti-inflammatory effects of perioperative statin therapy.

PMID- 22467069
TI  - Perioperative statin therapy: understanding the evidence in a Bayesian context.

PMID- 22467070
TI  - Electrostatic polarization is critical for the strong binding in streptavidin
      biotin system.
AB  - The origin of strong affinity of biotin and its analogs binding to (strept)avidin
      is still the subject of an ongoing controversy. In this work, thermodynamic
      integration is carried out to study of the difference of binding free energies
      between biotin and iminobiotin to streptavidin. Three atomic charge schemes are
      implemented and compared. One is the traditional AMBER charge, and the other two,
      termed the polarized protein-specific charge, are based on a linear scaling
      quantum mechanical method and a continuous solvation model and have polarization
      effect partially or fully included. The result indicates that when nonpolarized
      AMBER force field is applied, the result is much underestimated. When electronic
      polarization is gradually included, the difference of binding affinity increases
      along with it. Using the linear-response approximation to eliminate the error in
      self-charging process, the corrected binding affinity agrees well with the
      experimental observation. This study is direct evidence indicating that
      polarization effect is critical for the strong binding in streptavidin-biotin
      system.

PMID- 22467071
TI  - Pulmonary angiomatosis and hemangioma in common dolphins (Delphinus delphis)
      stranded in Canary Islands.
AB  - Vascular tumors and disorders, like angiomatosis, are rarely described in
      cetacean species. A retrospective histological study was carried out on lung
      samples from 35 common dolphins (Delphinus delphis) stranded in the Canary
      Islands coasts looking for morphological vascular changes and likely related
      causes. Twenty-five out of thirty-five (71%) common dolphins showed focal or
      multifocal angiomatosis-like lesions. A high association between this type of
      vascular proliferation and parasitic infestation was observed. In addition, a
      single pulmonary cavernous hemangioma not previously reported in common dolphins
      is presented.

PMID- 22467072
TI  - Successful induction of lactation in a barren Thoroughbred mare: growth of a foal
      raised on induced lactation and the corresponding maternal hormone profiles.
AB  - The purpose of this study was to demonstrate that a barren parous Thoroughbred
      mare with lactation induced by hormonal treatment can be introduced to an orphan
      foal at the same farm and that the mare can become pregnant after the end of the
      hormonal treatment. An additional purpose was to investigate the changes in the
      plasma concentrations of prolactin, estradiol-17beta, progesterone, follicle
      stimulating hormone, and luteinizing hormone before, during, and after hormonal
      treatment. The difference in body weight between the adopted foal and the control
      foals, which were at the same farm and raised by their natural mothers, was 17 kg
      at 24 weeks old, when the foals were weaned. However, the adopted foal and the
      control foals had almost the same weight at 35 weeks old and later. The first
      ovulation after hormonal treatment was confirmed 10 days after the end of
      hormonal treatment and then the normal estrous cycle resumed. Furthermore, the
      changes in plasma progesterone, estradiol-17beta, follicle-stimulating hormone,
      and luteinizing hormone showed regular patterns after the first ovulation.
      Conception was confirmed in the fifth ovulation. Meanwhile, another study
      demonstrated that conception was confirmed in the first ovulation after hormonal
      treatment. The present study is the first to demonstrate the hormonal profiles
      during and after induction of lactation in a Thoroughbred mare. This approach is
      useful for solving the economic and epidemic problems of introducing a nurse mare
      to an orphan foal.

PMID- 22467073
TI  - In vitro activities of antifungal agents against clinical isolates of
      dermatophytes from animals.
AB  - Although the susceptibility of dermatophytes to antifungal drugs is well
      documented in humans, the effectiveness in animals has not been previously
      investigated. The in vitro susceptibility of 54 clinical isolates from animal
      dermatophytoses to ketoconazole (KTZ), itaconazole (ITZ) and terbinafine (TFN)
      was measured using microdilution assay (CLSI M38-A2 test) and by the E-test (KTZ
      and ITZ). All 3 drugs showed antifungal activity, while KTZ displayed the
      broadest minimum inhibition concentration (MIC) range (0.125-16 MUg/ml) against
      M. canis and M. gypseum. The MIC of KTZ and ITZ was almost the same for human and
      animal isolates of T. mentagrophytes and T. rubrum. The MIC of TFN was almost the
      same for dermatophytes isolated from humans and animals.

PMID- 22467074
TI  - Three cases of idiopathic sterile pyogranulomatous inflammation of epidural fat
      in Miniature Dachshunds.
AB  - Progressive ataxia and paralysis in three Miniature Dachshunds were found to be
      caused by idiopathic sterile pyogranulomatous inflammation of epidural fat
      between T5 and L4. All dogs were managed by hemilaminectomy and removal of
      epidural compressive material. Surgical findings and histopathological evaluation
      were necessary to diagnose epidural pyogranulomatous inflammation. A dog did not
      regain motor and sensor function after the surgery. Two dogs had exhibited
      improved neurological function after the surgery, but they recurred. Oral
      cyclosporine treatment was useful for their long remission. Idiopathic sterile
      pyogranulomatous inflammation of epidural fat can be considered to be a cause of
      thoracolumbar myelopathy in dogs.

PMID- 22467075
TI  - Three different KRAS statuses in three synchronous colorectal cancers.
AB  - Treatments with monoclonal antibodies targeting the epidermal growth factor
      receptors (EGFR) have improved the prognosis of metastatic colorectal cancer
      (CRC). Mutated KRAS status is predictive of resistance to anti-EGFR agents and
      allows the selection of KRAS wild-type patients who may benefit from these
      targeted therapies. We report an original case of metastatic CRC including three
      synchronous primary tumors with three different KRAS statuses. We discuss the
      possible therapeutic impact of this clinical case and the role of multiple
      samplings for KRAS status determination.

PMID- 22467077
TI  - Non-small cell lung cancer histological subtype has prognostic impact in patients
      with brain metastases.
AB  - In patients with brain metastases from non-small cell lung cancer, the prognostic
      impact of primary tumour histology, a feature with increasing implications for
      choice of systemic therapy, is not well defined. Therefore, a multi-institutional
      analysis was performed: retrospective uni- and multivariate analyses in 209
      patients treated with different approaches including surgery and radiosurgery.
      While squamous cell and large cell carcinoma patients had comparable survival,
      those with adenocarcinoma survived significantly longer. In multivariate models,
      adenocarcinoma histology was confirmed as independent prognostic factor, which
      complements both recursive partitioning analysis (RPA) classes and diagnosis
      specific graded prognostic assessment (GPA). When evaluated together with primary
      tumour control, extracranial metastases, number of brain metastases, age and
      performance status as individual covariates rather than RPA or GPA score,
      adenocarcinoma histology again emerged as significant prognostic factor. A
      significant but small survival advantage for patients with adenocarcinoma was
      evident already in the time period before drugs such as pemetrexed and epidermal
      growth factor receptor tyrosine kinase inhibitors were available. However, the
      gap has widened in recently treated patients. Comparable to patients without
      brain metastases, primary tumour histology should be taken into account when
      assessing patients' prognosis and recommending treatment strategy.

PMID- 22467076
TI  - P-cadherin expression and basal-like subtype in breast cancers.
AB  - Breast cancer is considered as one of the multifactorial diseases. The aim of the
      current study is to investigate the association between P-cadherin and molecular
      subtypes of breast cancer, especially the basal-like subtype. Two hundred and
      thirteen breast-invasive ductal carcinomas were involved in this study. The
      expressions of P-cadherin were detected via immunohistochemistry. The 213 cases
      were divided into luminal A, luminal B, HER2 overexpression subtype, and normal
      breast-like and basal-like subtypes according to the standard of molecular breast
      cancer subtypes. In addition, the expressions of CK5/6 and CK14 were detected to
      distinguish between the normal breast-like and the basal-like subtypes. P
      cadherin expression was found in 91 cases of 213 breast-invasive ductal
      carcinomas, with a positive rate of 42.7%. P-cadherin correlated negatively with
      estrogen receptor (ER) (p=0.001) and progesterone receptor (p=0.001), whereas it
      positively correlated with histologic grade (p=0.003), NPI (p=0.005), p53
      (p=0.038), and Ki67 (p=0.022). P-cadherin expression showed a strong correlation
      with recurrence and distant metastasis (p=0.009), and invasion of the vascular
      and soft tissues (p=0.004). Moreover, P-cadherin expression existed in the basal
      like and non-basal-like subtypes. During prognosis, P-cadherin expression was
      associated with decreased disease-free survival in patients (p=0.009) and overall
      survival (OS) (p=0.005). In addition, multivariate analysis showed that tumor
      grade (p=0.021), ER (p=0.015), clinical stage (p=0.001), and P-cadherin (p=0.033)
      were significant predictors of OS. The current data suggest that P-cadherin may
      be used to distinguish the basal-like subtype and to predict the outcome in view
      of the relationship with DFS and OS. Furthermore, P-cadherin expression may be
      useful in making treatment decisions.

PMID- 22467078
TI  - Primary neuroendocrine breast cancer, how much do we know so far?
AB  - Primary neuroendocrine cancer of the breast (NECB) is an extremely rare tumor. In
      2003, the World Health Organization (WHO) recognized this category with three
      well-described subtypes: small cell, large cell, and carcinoid-like carcinoma;
      very few peer-review publications based on the WHO definition were encountered in
      the literature, and we conducted a literature search to investigate the reported
      incidence, diagnosis, prognosis, hormone receptor status, and treatment options
      for this rare tumor. Confirming the breast as an origin of neuroendocrine tumor
      represents a challenge. The diagnosis is mainly dependent on the exclusion of
      other extra-mammary organs based on clinical, radiological, and pathological
      data. Except for the very rare type small cell carcinoma, estrogen and
      progesterone receptors were reported to be expressed in 90 and 83% of NECB,
      respectively. It is hypothesized that primary breast neuroendocrine carcinoma
      differentiates from the epithelial cells during the carcinogenesis process; the
      prognosis of non-small cell primary NECB seems to improve as the amount of
      mucinous component increases in the tumor specimen. Management similar to
      interventions utilized to manage the usual ductal-type carcinoma has been
      attempted in the past, such as chemotherapy and hormonal therapy; however, due to
      the rarity of the tumor, none of the published studies are randomized nor do they
      have a large number of patients. Additionally, none of reports analyzed NECB
      based on its distinct subtypes. These limitations make recommendations largely
      based on anecdotal and small observatory studies and call for the need for
      further research in this extremely rare tumor.

PMID- 22467079
TI  - Metformin and hepatic carcinogenesis.
AB  - Retrospective, hypothesis-generating population studies suggest that diabetics
      treated with metformin have a substantially reduced risk of several cancers,
      including hepatoma, relative to diabetics on other therapies. In this issue of
      the journal (beginning on page 544), Bhalla and colleagues contribute to the
      growing literature on metformin effects in experimental carcinogenesis models,
      showing reduced carcinogen-induced hepatoma in mice. The clinical need to develop
      novel prevention strategies for hepatoma is obvious, given an increasing
      prevalence and poor prognosis. The clues that metformin or related biguanides may
      have utility in this area justify accelerated laboratory research, as more data
      concerning mechanism, pharmacokinetics, and predictors of efficacy will help to
      optimize the design of clinical trials.

PMID- 22467080
TI  - Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic
      lipogenesis.
AB  - A number of factors have been identified that increase the risk of hepatocellular
      carcinoma (HCC). Recently it has become appreciated that type II diabetes
      increases the risk of developing HCC. This represents a patient population that
      can be identified and targeted for cancer prevention. The biguanide metformin is
      a first-line therapy for the treatment of type II diabetes in which it exerts its
      effects primarily on the liver. A role of metformin in HCC is suggested by
      studies linking metformin intake for control of diabetes with a reduced risk of
      HCC. Although a number of preclinical studies show the anticancer properties of
      metformin in a number of tissues, no studies have directly examined the effect of
      metformin on preventing carcinogenesis in the liver, one of its main sites of
      action. We show in these studies that metformin protected mice against chemically
      induced liver tumors. Interestingly, metformin did not increase AMPK activation,
      often shown to be a metformin target. Rather metformin decreased the expression
      of several lipogenic enzymes and lipogenesis. In addition, restoring lipogenic
      gene expression by ectopic expression of the lipogenic transcription factor
      SREBP1c rescues metformin-mediated growth inhibition. This mechanism of action
      suggests that metformin may also be useful for patients with other disorders
      associated with HCC in which increased lipid synthesis is observed. As a whole
      these studies show that metformin prevents HCC and that metformin should be
      evaluated as a preventive agent for HCC in readily identifiable at-risk patients.

PMID- 22467082
TI  - The use and reporting of WOMAC in the assessment of the benefit of physical
      therapies for the pain of osteoarthritis of the knee: findings from a systematic
      review of clinical trials.
AB  - OBJECTIVE: For the purposes of meta-analysis and network meta-analysis, the use
      of standard outcome measures is ideal. In OA research, the WOMAC was developed as
      an OA-specific measure of disability. It includes a pain subscale. In 1994 a
      consensus meeting recommended the use of WOMAC as a primary measure of efficacy
      in OA. In the context of a review of the efficacy of physical interventions for
      the relief of the pain of OA of the knee, we investigated the use of WOMAC.
      METHODS: A systematic review (December 2009-January 2010) identified trials that
      used the WOMAC outcome. These were investigated for correct use and clear
      reporting of the WOMAC pain subscale and the WOMAC index. RESULTS: The WOMAC pain
      subscale was used in 45% of the 134 trials. Reporting of the exact method of
      administering the WOMAC pain subscale was poor in many cases: in 53% of trials
      the reporting of the type of WOMAC scale used was inadequate; the score range was
      reported ambiguously in 38% of trials, with a further 10% being completely
      unclear. Similar less than optimal reporting of the WOMAC index was found.
      CONCLUSION: Poor reporting of both the WOMAC pain subscale and the WOMAC index
      resulted in significant uncertainty in the interpretation of the results of
      individual trials and limited their contribution to evidence synthesis. Improved
      adherence with the standard use of the WOMAC scoring system, with clear reporting
      of it in trials of OA of the knee should be encouraged.

PMID- 22467081
TI  - Metformin prevents the development of oral squamous cell carcinomas from
      carcinogen-induced premalignant lesions.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a major public health concern.
      The recent identification of the mTOR complex 1 (mTORC1) signaling pathway as a
      highly prevalent molecular signature underlying HNSCC pathogenesis has provided
      the foundation to search for novel therapeutic approaches to prevent and treat
      HNSCC. Here, we asked whether metformin, the most widely used medication for the
      treatment of type II diabetes, which acts in part by stimulating the AMP
      activated protein kinase (AMPK) signaling pathway thereby reducing mTORC1
      activity, may lower the risk of HNSCC development. Indeed, we show that metformin
      reduces the growth of HNSCC cells and diminishes their mTORC1 activity by both
      AMPK-dependent and -independent mechanisms. We also optimized an oral-specific
      carcinogenesis mouse model that results in the accumulation of multiple oral
      premalignant lesions at the end of the carcinogen exposure, some of which then
      spontaneously progress into HNSCC. Using this mouse model, we observed that
      metformin specifically inhibits mTORC1 in the basal proliferating epithelial
      layer of oral premalignant lesions. Remarkably, metformin prevented the
      development of HNSCC by reducing significantly the size and number of carcinogen
      induced oral tumoral lesions and by preventing their spontaneous conversion to
      squamous cell carcinomas. Collectively, our data underscore the potential
      clinical benefits of using metformin as a targeted chemopreventive agent in the
      control of HNSCC development and progression.

PMID- 22467083
TI  - Are syndesmophytes most prevalent in the lumbar or in the cervical spine in
      patients with ankylosing spondylitis and do they develop in a specific direction?
AB  - OBJECTIVES: To describe the distribution of prevalent syndesmophytes and bridges,
      and the occurrence of new ones in a prevalence cohort of patients with AS.
      METHODS: Clinical and radiological data from 132 patients from the Outcome in
      Ankylosing Spondylitis International Study of which complete sets of radiographs
      were available at baseline and at 2- and 4-year follow-up were used. RESULTS: At
      baseline, 81 (61%) patients, of which 17 (45%) were females and 64 (65%) males (P
      = 0.03), had prevalent (bridging) syndesmophytes. Both syndesmophytes and bridges
      were found at all vertebral levels. Syndesmophytes were more frequently seen in
      the cervical spine compared with the lumbar spine (mean per vertebral level 17.5
      vs 11.2%, respectively, P = 0.01). Bridges were more frequently seen in the
      lumbar spine compared with the cervical spine (mean per vertebral level 16.9% vs
      12.1%, P = 0.02). With increasing disease duration more (bridging) syndesmophytes
      were found, occurring similarly at the lumbar and cervical spines. After 2- and 4
      years of follow-up, new (bridging) syndesmophytes developed throughout the entire
      cervical and lumbar spines. CONCLUSION: In general, syndesmophytes occur more
      frequently in the cervical spine and bridges more frequently in the lumbar spine,
      but neither a specific predilection site nor any particular order for occurrence
      and development of syndesmophytes could be detected.

PMID- 22467084
TI  - Articular involvement in systemic sclerosis.
AB  - Articular involvement is frequent in SSc. It contributes to disability and
      compromises patients' quality of life. Different aspects of articular involvement
      have been described, ranging from arthralgia and arthritis to joint contracture
      and tendon sheath involvement. Recent cohort studies examining clinical and
      radiographic aspects of SSc have clarified the frequency of articular involvement
      and identified subsets of SSc patients with a higher risk of developing joint
      involvement. They have also highlighted the potential contribution of
      inflammatory arthritis to early SSc. Some pilot studies have underlined the
      potential usefulness of new imaging tools, such as ultrasonography and MRI for a
      better evaluation of joint involvement in SSc. Current treatment strategies for
      SSc-related inflammatory joint disease have not been evaluated in randomized
      controlled trials and generally derive from RA. MTX associated with low-dose CSs
      is the standard care for arthritis. Other treatment strategies (LEF and i.e.
      biologics borrowed from RA) may bring new opportunities to treat SSc-related
      arthritis and even SSc per se. However, the first step will be to study and
      validate outcome criteria in this insufficiently studied field.

PMID- 22467085
TI  - Tocilizumab treatment in a patient suffering from rheumatoid arthritis and
      concomitant chronic hepatitis C infection.

PMID- 22467086
TI  - Spatially defined disruption of motor imagery performance in people with
      osteoarthritis.
AB  - OBJECTIVES: To determine whether motor imagery performance is disrupted in
      patients with painful knee OA and if this disruption is specific to the location
      of the pain. METHODS: Twenty patients with painful knee OA, 20 patients with arm
      pain and 20 healthy pain-free controls undertook a motor imagery task in which
      they made left/right judgements of pictured hands and feet. Accuracy and reaction
      time of judgements were compared between groups and pain locations (side: left vs
      right; site: upper vs lower). RESULTS: Patients with knee pain were less accurate
      (P < 0.01) than healthy controls, but not different from people with arm pain
      (all P > 0.11). There were no differences in reaction time between groups (P =
      0.64). Further, there was no effect of side or site of pain on reaction time (P =
      0.43, 0.54, respectively) and no effect of site of pain on accuracy of left/right
      judgements (P = 0.12). However, there was an interaction effect of side of pain
      on accuracy of left vs right images (P = 0.03). If left-sided pain was present,
      accuracy was lower when images showed left hands/feet than when images showed
      right hands/feet. CONCLUSION: Motor imagery performance is disrupted in patients
      with knee OA, but is also disrupted in patients with arm pain. Accuracy of
      left/right judgements is disrupted in a spatially defined manner, raising the
      important possibility that brain-grounded maps of peripersonal space contribute
      to the cortical proprioceptive representation.

PMID- 22467087
TI  - Comparison of surgical decompression and local steroid injection in the treatment
      of carpal tunnel syndrome: 2-year clinical results from a randomized trial.
AB  - OBJECTIVE: To compare the efficacy of surgical decompression vs local steroid
      injection in the treatment of idiopathic CTS. METHODS: This is an open,
      prospective, randomized clinical trial. We studied the effects of surgical
      decompression vs local steroid injection in 163 wrists with a clinical diagnosis
      and neurophysiological confirmation of CTS, with an extended follow-up of 2
      years. The primary end point was the percentage of wrists that reached a >= 20%
      improvement in the visual analogue scale score for nocturnal paraesthesias.
      Statistical analysis was done by Student's t-test for continuous variables and by
      chi-square test for categorical variables. Analyses were performed on an intent
      to-treat basis. P < 0.05 were considered statistically significant. RESULTS: Both
      treatment groups had comparable severity of CTS at baseline. Eighty wrists were
      randomly assigned to surgical decompression and 83 wrists to local steroid
      injection. Fifty-five wrists in the surgery group and 48 wrists in the injection
      group completed the 2-year follow-up. In the intent-to-treat analysis, at 2-year
      follow-up, 60% of the wrists in the injection group vs 69% in the surgery group
      reached a 20% response for nocturnal paraesthesias (P < 0.001). CONCLUSION: Our
      findings suggest that both local steroid injection and surgical decompression are
      effective treatments in alleviating symptoms in primary CTS at 2-year follow-up.
      Surgery has an additional benefit in the 2-year follow-up, although clinical
      relevance of those differences remains to be defined. TRIAL REGISTRATION: Current
      Controlled Trials, www.controlled-trials.com, ISRCTN26264638.

PMID- 22467088
TI  - Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels?
AB  - Deficiency of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and excessive fibroblast
      growth factor (FGF23) are suggested to be associated with increased mortality in
      patients with chronic kidney disease (CKD). Generally, 24-hydroxylation has been
      considered the first step in the degradation pathway of 1,25(OH)(2)D and 25(OH)D.
      24,25-dihydroxyvitamin D [24,25(OH)(2)D] was believed to be a degradation
      product, with no important biological effects. However, some data have
      accumulated showing that 24,25(OH)(2)D has biological effects on its own. Under
      conditions of eucalcemia, the synthesis of 24,25(OH)(2)D is increased, and the
      synthesis of 1,25(OH)(2)D is decreased. In patients with CKD, both high
      parathyroid hormone levels, which decrease the activity of enzyme CYP24A1 (24
      hydroxylase), and high FGF23 levels, which increase the activity of enzyme
      CYP24A1, were often detected. However, information about 24,25(OH)(2)D levels in
      these patients is very limited. Whether compensatory changes in levels of FGF23
      and 24,25(OH)(2)D in CKD patients are protective or harmful remain unknown
      issues. Therefore, more studies are needed to identify the nature of the
      interactions between these molecules and to fully elucidate their clinical
      significance.

PMID- 22467090
TI  - An experience with midazolam anaphylactoid reaction.

PMID- 22467089
TI  - Hyperphosphatemia is associated with overt proteinuria in non-diabetic patients
      with late-stage chronic kidney disease: a cross-sectional study.
AB  - PURPOSE: Proteinuria plays an important role in the progression of chronic kidney
      disease (CKD), as well as a powerful predictor of cardiovascular morbidity and
      mortality. The aim of our study was to investigate the potential determinants
      associated with overt proteinuria in non-diabetic patients with late-stage CKD.
      METHODS: Between January 2006 and September 2011, a total of 418 non-diabetic
      patients with CKD stage 3-5 were enrolled from the outpatient department of
      nephrology. Urinary protein-to-creatinine ratio and serum phosphorus were
      determined. Other laboratory parameters, associated comorbidities, medication
      use, body mass index, and blood pressure were also assessed. RESULTS: The mean
      age of the patients was 66.7 +/- 14.0 years. In multiple logistic regression
      analysis and adjusting for established risk factors, the odds ratios for overt
      proteinuria were 3.96 (95 % confidence interval, 1.80-8.76; p = 0.001) for higher
      serum phosphorus level (>=4.3 mg/dl) and 3.56 (95 % confidence interval, 1.47
      8.63; p = 0.005) for hypercholesterolemia (>=217 mg/dl), compared to subjects
      with serum phosphorus <3.3 mg/dl and cholesterol level 158-184 mg/dl. The similar
      significant findings remained robust in individuals not receiving phosphate
      binder. CONCLUSIONS: Hyperphosphatemia and high serum cholesterol are associated
      with overt proteinuria in non-diabetic patients with late-stage CKD. Further
      studies should clarify whether this relation is causal and whether serum
      phosphorus level should be a new therapeutic target for proteinuria reduction.

PMID- 22467091
TI  - Nanoelectronics, sensors and single molecule biophysics.

PMID- 22467092
TI  - A methodological look at the controversy about the influence of salt intake on
      cardiovascular risk.

PMID- 22467093
TI  - Abdominal wall hematoma related to severe cough in a patient under antiaggregant
      and anticoagulant therapy.

PMID- 22467094
TI  - Postmenopausal osteoporosis treatment with antiresorptives: effects of
      discontinuation or long-term continuation on bone turnover and fracture risk--a
      perspective.
AB  - Osteoporosis may be a lifelong condition. Robust data regarding the efficacy and
      safety of both long-term osteoporosis therapy and therapy discontinuation are
      therefore important. A paucity of clinical trial data regarding the long-term
      antifracture efficacy of osteoporosis therapies necessitates the use of surrogate
      endpoints in discussions surrounding long-term use and/or discontinuation. Long
      term treatment (beyond 3-4 years) may produce further increases in bone mineral
      density (BMD) or BMD stability, depending on the specific treatment and the
      skeletal site. Bisphosphonates, when discontinued, are associated with a
      prolonged reduction in bone turnover markers (BTMs), with a very gradual increase
      to pretreatment levels within 3 to 60 months of treatment cessation, depending on
      the bisphosphonate used and the prior duration of therapy. In contrast, with
      nonbisphosphonate antiresorptive agents, such as estrogen and denosumab, BTMs
      rebound to above pretreatment values within months of discontinuation. The
      pattern of BTM change is generally mirrored by a more or less rapid decrease in
      BMD. Although the prolonged effect of some bisphosphonates on BTMs and BMD may
      contribute to residual benefit on bone strength, it may also raise safety
      concerns. Adequately powered postdiscontinuation fracture studies and conclusive
      evidence on maintenance or loss of fracture benefit is lacking for
      bisphosphonates. Similarly, the effects of rapid reversal of bone turnover upon
      discontinuation of denosumab on fracture risk remain unknown. Ideally, studies
      evaluating the effects of long-term treatment and treatment discontinuation
      should be designed to provide head-to-head "offset" data between bisphosphonates
      and nonbisphosphonate antiresorptive agents. In the absence of this, a clinical
      recommendation for physicians may be to periodically assess the benefits/risks of
      continuation versus discontinuation versus alternative management strategies.

PMID- 22467095
TI  - Cytoplasmatic compartmentalization by Bcr-Abl promotes TET2 loss-of-function in
      chronic myeloid leukemia.
AB  - The loss-of-function of ten-eleven-translocation (TET) 2, a Fe(2+) -oxoglutarate
      dependent dioxygenase catalyzing 5 methyl cytosine (5mC) conversion into 5
      hydroxymethylcytosine (5hmC), contributes to the hematopoietic transformation in
      vivo. The aim of our study was to elucidate its role in the phenotype of chronic
      myeloid leukemia (CML), a myeloproliferative disease caused by the Bcr-Abl
      rearranged gene. We first confirmed TET2 interaction with the Bcr-Abl protein
      predicted by a Fourier-based bioinformatic method. Such interaction led to TET2
      cytoplasmatic compartmentalization in a complex tethered by the fusion protein
      tyrosine kinase (TK) and encompassing the Forkhead box O3a (FoxO3a) transcription
      factor. We then focused the impact of TET2 loss-of-function on epigenetic
      transcriptional regulation of Bcl2-interacting mediator (BIM), a pro-apoptotic
      protein transcriptionally regulated by FoxO3a. BIM downregulation is a critical
      component of CML progenitor extended survival and is also involved in the disease
      resistance to imatinib (IM). Here we reported that TET2 release from Bcr-Abl
      protein following TK inhibition in response to IM triggers a chain of events
      including TET2 nuclear translocation, re-activation of its enzymatic function at
      5mC and recruitment at the BIM promoter followed by BIM transcriptional
      induction. 5hmC increment following TET2 re-activation was associated with the
      reduction of histone H3 tri-methylation at lysine 9 (H3K9me3), which may
      contribute with DNA de-methylation reported elsewhere to recast a permissive
      epigenetic "landscape" for FoxO3a transcriptional activity.

PMID- 22467097
TI  - Cytokeratin-19 fragments, nucleosomes and neuron-specific enolase as early
      measures of chemotherapy response in non-small cell lung cancer.
AB  - AIM: To investigate the reduction in the serum level of cytokeratin-19 fragments
      (CYFRA 21-1), nucleosomes and neuron-specific enolase (NSE) as early measures of
      the response to chemotherapy in non-small cell lung cancer (NSCLC). METHODS:
      Forty-two consecutive patients with locally advanced NSCLC were included. All
      patients received platinum-based chemotherapy. Staging investigations and
      quantification of CYFRA 21-1, nucleosomes and NSE (using enzyme-linked
      immunosorbent assay, ELISA) were performed before the start of treatment and
      after the second cycle of chemotherapy. According to the response to
      chemotherapy, patients were classified into 3 groups: (I) disease regression,
      (II) stable disease, and (III) progressive disease. The reduction in the levels
      of tumor markers was correlated with the response to chemotherapy. RESULTS: After
      the second cycle of chemotherapy, groups I and II had significantly decreased
      serum levels of CYFRA 21-1 (p<0.05). Similarly, the concentration of nucleosomes
      was significantly lower than the baseline levels in groups I (p=0.0008) and II
      (p=0.003). The reduction of both CYFRA 21-1 and nucleosome levels was not
      significant for patients in group III. In all groups the reduction of NSE levels
      in response to chemotherapy was not significant. As a marker of response to
      chemotherapy, CYFRA 21-1 showed the highest sensitivity (88.9%) and specificity
      (77.4%) compared with nucleosomes (77.8% and 58.1% respectively) and NSE (66.7%
      and 51.8% respectively). CONCLUSION: The reduction in the serum level of CYFRA 21
      1 and nucleosomes may be used for early identification of NSCLC patients with
      good response to chemotherapy.

PMID- 22467098
TI  - Glycoprotein electrophoretic patterns have potential to monitor changes
      associated with neoplastic transformation in oral cancer.
AB  - Alterations in glycoproteins, important cell surface constituents, have long been
      associated with various malignancies. The present investigation therefore
      explored the clinical significance of a glycoproteomics approach in patients with
      oral precancerous conditions (OPC) and patients with oral cancer. The study
      included 80 oral cancer patients, 50 patients with OPC, and 84 controls. Native
      polyacrylamide gel electrophoresis followed by Schiff's staining was carried out
      to study the alterations in glycoproteins. The results showed significant
      elevation (p<0.0001) of 192 kDa, 170 kDa, 116 kDa and 44 kDa glycoproteins in
      oral cancer patients and patients with OPC compared with controls. The odds ratio
      indicated a significantly higher risk for oral cancer among users and especially
      chewers of tobacco. The levels of all the glycoprotein bands (192 kDa, 170 kDa,
      116 kDa and 44 kDa) were higher in patients with a habit of tobacco use (WHT)
      than in patients with no habit of tobacco (NHT) and were also higher in WHT
      controls than in NHT controls. Moreover, a 230 kDa glycoprotein consistently
      appeared only in individuals with tobacco habits and an increasing trend was
      observed from WHT controls to patients with OPC to WHT oral cancer patients. In
      conclusion, the results indicated the potential utility of glycoprotein
      alterations in monitoring sequential changes occurring due to tobacco consumption
      during neoplastic transformation.

PMID- 22467099
TI  - Elevation of CA 125 and CA 19-9 in patients with end-stage liver disease.
AB  - BACKGROUND: The serum tumor markers CA 19-9 and CA 125 are the serologic markers
      used for the monitoring of biliopancreatic and ovarian cancer, respectively. They
      are reported to be elevated in a variety of nonneoplastic clinical situations,
      including end-stage liver disease (ESLD). However, their prevalence and degree of
      elevation in patients with ESLD remained unclear. AIM: To examine the prevalence
      and degree of elevation of CA 19-9 and CA 125 in patients with ESLD and to
      determine their association with severity of liver disease. METHODS:
      Retrospective analysis of 161 patients with ESLD that were evaluated for liver
      transplantation at our institution between March 2009 and December 2010. The mean
      age was 55.15 +/- 8.75 years and 107 (66.4%) of the patients were men. Serum CA
      19-9 and CA 125 levels were determined during evaluation of their candidacy for
      liver transplantation. RESULTS: Eighty-three (51.5%) patients had elevated CA 125
      and 44 (53%) of them had a serum concentration >5 times the upper limit of normal
      (ULN). Elevated CA 125 was associated with alcoholic liver disease, high Model
      for End-Stage Liver Disease (MELD) score, and presence of ascites. Similarly, 37
      (23%) patients had elevated CA 19-9 and 8 (21.6%) of them had a serum
      concentration >5 times ULN. Elevation of CA 19-9 was associated with high MELD
      score. CONCLUSIONS: CA 125 and CA 19-9 concentrations were elevated in 51.5% and
      23% of patients with ESLD, respectively. Although the definite etiology remained
      unclear, their elevation was associated with the pathological conditions
      associated with advanced liver disease. Further studies are needed to clarify the
      underlying mechanism(s) responsible for their increased levels.

PMID- 22467100
TI  - Murine double minute clone 2,309T/G and 285G/C promoter single nucleotide
      polymorphism as a risk factor for breast cancer: a Polish experience.
AB  - BACKGROUND: Breast cancer is a multifactorial disease caused by complex
      interactions between genetic and environmental factors. Recently, a functional
      polymorphism, MDM2 285G>C (rs117039649), has been discovered. This polymorphism
      antagonizes the effect of the 309T>G (rs2279744) polymorphism on the same gene,
      resulting in decreased MDM2 transcription. METHODS: The MDM2 285G>C and 309T>G
      polymorphisms were identified by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) and sequencing analysis in women with breast
      cancer (n=468) and controls (n=550). RESULTS: The odds ratio (OR) for breast
      cancer patients with the MDM2 285C/C and 285G/C genotypes was 0.4768 (95%
      confidence interval [CI] 0.2906-0.7824; p=0.0033, pcorr=0.0066). We also found a
      significantly lower frequency of the MDM2 285C allele in patients with breast
      cancer than in controls: the OR for the C allele in patients with breast cancer
      was 0.4930 (95% CI=0.3059-0.7947, p=0.0031, pcorr=0.0062). The p value of the chi
      square test for the trend observed for the MDM2 285G>C polymorphism was
      statistically significant (ptrend=0.0036). The statistical power of this study
      amounted to 85% for the G/C or C/C genotypes and 85% for the C allele. However,
      we did not observe significant differences between the distribution of MDM2
      309T>G genotypes and alleles in patients with breast cancer and healthy controls.
      CONCLUSION: In a sample of the Polish population, we observed that the MDM2 285C
      gene variant may be a significant protective factor against breast cancer.

PMID- 22467101
TI  - Expression and prognostic relevance of STAT3 and cyclin D1 in non-small cell lung
      cancer.
AB  - AIM: To guide clinicians in selecting treatment options for patients with non
      small cell lung cancer (NSCLC), it is desirable to have reliable markers
      predicting clinical outcome. This study analyzed the correlation between signal
      transducer and activator of transcription 3 (STAT3) and cyclin D1 in NSCLC and
      their association with clinicopathological features and survival. METHODS: We
      investigated 65 specimens of NSCLC tissues by immunohistochemistry using STAT3
      and cyclin D1 antibodies. First we determined the correlation between STAT3 and
      cyclin D1 expression and the clinicopathological features of the tumor. Then we
      assessed the prognostic relevance of STAT3 and cyclin D1. RESULTS: A significant
      correlation was found between high levels of STAT3 expression and the degree of
      tumor differentiation. Additionally, a significant positive correlation was found
      between the expression of STAT3 and cyclin D1 (r=0.405, p=0.001). The
      overexpression of STAT3 and the presence of metastasis were significantly
      associated with shorter overall survival in univariate analysis (p=0.028 and
      p=0.036, respectively). Multivariate analysis confirmed that STAT3 expression was
      an independent prognostic factor (p=0.001). CONCLUSIONS: STAT3 might be
      correlated with tumor differentiation, and its elevated expression may be an
      adverse prognostic indicator for patients with NSCLC. Activation of the
      STAT3/cyclin D1 signaling pathway may be attributed to the malignant
      transformation of NSCLC and may represent a possible target for therapy.

PMID- 22467103
TI  - Effects of antidepressants and mood stabilizers on serum levels of adiponectin.
AB  - The effect of antidepressants and mood stabilizers on serum levels of adiponectin
      was investigated. Fluvoxamine (30 and 50 mg/kg/day) or lithium (40 and 60
      mg/kg/day) was dissolved in distilled water and administered orally to rats every
      day for 4 weeks. Fluvoxamine (50 mg/kg/day) alone significantly elevated the
      serum level of adiponectin, but no significant difference was found between other
      drug-treated groups and the control group. This difference of these drugs'
      effectiveness on serum adiponectin might contribute to their differences of
      action mechanisms and therapeutic effects.

PMID- 22467104
TI  - Effect of functional stabilization training on balance and motor patterns in a
      patient with Charcot-Marie-Tooth disease.
AB  - OBJECTIVES: Balance and motor disturbances are significant symptoms commonly
      associated with hereditary motor and sensory neuropathy (HMSN), also known as
      Charcot-Marie-Tooth disease (CMT). Although CMT is a progressive neurological
      disease, comprehensive physiotherapeutic strategies may improve balance and motor
      patterns, and, therefore, enhance the quality of life (ADL). CASE PRESENTATION: A
      55-year-old HMSN patient with confirmed CMT X phenotype was evaluated for
      locomotor stability on a stabilometric platform. Stability tests were repeated
      after a 3-week, intensive in-patient rehabilitation program and the results were
      compared. CONCLUSIONS: Improvements in "modified clinical testing of sensory
      interaction on balance", "limits of stability" and "forward lunge" tests were
      observed. Subjectively, the patient noted a significant improvement in both
      balance and gait.

PMID- 22467105
TI  - Do novel adipokines play a causative or only modulating role in the pathogenesis
      of obesity and metabolic disorders?
AB  - Adipose tissue is an endocrine and paracrine organ that releases a large number
      of bioactive mediators. Approximately 100 adipokines have been identified
      including cytokines, chemokines, growth factors and enzymes. The use of
      adipoproteomic analyses resulted in new findings and, in consequence, the number
      of new adipokines is rising rapidly. Novel adipokines such as visfatin, vaspin
      and omentin were discovered about five years ago. Visfatin and vaspin production
      and secretion take place in adipocytes, but omentin comes from the stromal cells
      of adipose tissue. Several differences are noticeable between these adipokines
      especially in correlation with obesity as visfatin and vaspin serum levels
      increase in obese subjects while omentin serum levels decrease. It has been
      suggested that these adipokines act as insulin-sensitizers/insulin-mimetics.
      Increasing number of publications reporting the role of new adipokines does not
      allow to assess clearly the influence of those adipokines on the pathogenesis of
      obesity.

PMID- 22467106
TI  - Associations between marginal periodontitis and rheumatoid arthritis.
AB  - Chronic destructive periodontitis is no longer considered to be just a local
      inflammatory process afflicting the periodontal tissues, but a systemic
      infection. Bacteria, their products and various pro-inflammatory cells and
      substances can penetrate into the blood stream and infect distant organs and
      structures. Periodontitis and rheumatoid arthritis indicate several common histo
      pathological correlations, as the destroyed osseous tissues and cartilages are
      permanently washed with inflammatory fluid full of proteolytic and osteolytic
      substances. Although exact causal and molecular associations between both
      diseases have not been explained yet, there are some common etiopathogenic
      correlations that can have influence on relationship between both diseases. Among
      these factors belong: a positive finding of common genes, genetic polymorphisms
      and hyper-inflammatory types of some immune competent cells and molecules, common
      cytokine profiles and increased concentrations of pro-inflammatory mediators in
      periodontal and joint structures. Periodontitis and some periodontal pathogens
      can influence various auto-immune reactions connected with rheumatoid arthritis
      (RF, anti-CCP). Possible causal associations are indicated in some studies
      dealing with treatment of RA, when a beneficiary effect of RA treatment led to
      improvement of some periodontal parameters. This relationship works both ways;
      the periodontal therapy had positive influence on some markers of rheumatoid
      arthritis. This provides sufficient theoretic evidence to perform professional
      and personal oral hygiene in a more active way.

PMID- 22467107
TI  - Salivary levels of oxytocin remain elevated for more than two hours after
      intranasal oxytocin administration.
AB  - OBJECTIVE: This is the first study investigating whether levels of oxytocin in
      saliva remained elevated after intranasal oxytocin administration for the
      duration of an experiment (in which neurobehavioral effects of oxytocin were
      observed) taking more than two hours. METHODS: Oxytocin levels were measured in
      saliva samples collected from 57 female participants right before (T0),
      approximately 11/4 h (T1), and approximately 21/4 h (T2) after intranasal
      administration of 16 IU of oxytocin or a placebo, using a double-blind, within
      subjects design. RESULTS: Average levels of oxytocin did not differ between
      conditions before use of the nasal spray, markedly increased only after oxytocin
      administration, and were still elevated after 21/4 h. CONCLUSION: Salivary levels
      of oxytocin remained persistently elevated over the course of our experiment,
      i.e. for more than two hours after intranasal oxytocin administration and over a
      time-period in which neurobehavioral effects of oxytocin are commonly observed.
      This suggests that salivary concentrations may be a valuable biomarker for
      oxytocin, and may help to explain its effects on brain activity, information
      processing, and behavior.

PMID- 22467108
TI  - Study of the APC gene function in the mouse APC+/APC1638N model.
AB  - OBJECTIVES: Familial adenomatous polyposis (FAP) is an autosomal dominant disease
      characterized by the presence of hundreds to thousands of benign polyps in the
      colon. If not removed prophylactically they represent a risk of developing
      malignant cancer with an almost 100% penentrance. FAP is induced by germline
      mutation in the APC gene. Tumorigenesis launched a second somatic mutation of APC
      gene allele, leading to synthesis of non-functional APC protein. One of the
      possibilities of cancer prevention could be an alternative gene therapy using
      bacteria as vectors for delivery of therapeutic protein molecules. MATERIAL AND
      METHODS: For this purpose mice model APC+/APC1638N with mutation in one allele
      murine homolog of the APC gene were used. Mice were fed orally commercial
      nutrition enriched with 0.5 ml PBS buffer with 5% milk containing 5*108
      recombinant bacterial cells DE3plys6 bearing plasmid with cloned APC gene twice a
      week during 42 weeks. Afterwords mice were killed by thiopental, gastrointestinal
      tracts were removed, microscopically, macroscopically inspected for
      polyps/neoplastic lesions and immunohistochemically investigated with polyclonal
      rabbit antibody against APC protein. RESULTS: We have cloned full-lenght APC gene
      into vector for expression in bacterial cells Escherichia coli BL21(DE3) and
      BL21(DE3) pLysS. Expression of the APC protein, induced by IPTG, was detected in
      protein extracts of three bacterial clones: DE3104-11, DE3pLys5, DE3pLys6. APC
      protein was identified by Western blot analysis using monoclonal and polyclonal
      antibodies against the APC protein. Bacteria of clone DE3pLys6 were orally
      administered to APC+/APC1638N mice with mutations in the APC gene. All transgenic
      mice without therapy developed adenomatous polyps in the gastrointestinal tract.
      Transgenic mice treated by oral administration of bacteria expressing functional
      APC protein developed polyps in 33.3%. The remaining four mice 66.7% were without
      polyps development. CONCLUSION: Administration of APC gene expressing by bacteria
      to transgenic mice with mutation in APC gene leads to reduction in the number of
      mice developing polyps in the gastrointestinal tract. The effect of bacterially
      expressed APC protein in elimination of intestinal polyps or tumors has been
      monitored. These are our preliminary results and for possible confirmation of our
      hypotheses still more research is needed.

PMID- 22467109
TI  - Levodopa in combination with carbidopa does not affect plasma arginine
      vasopressin levels in treatment-naive older patients with Parkinson's disease: A
      before-after study.
AB  - OBJECTIVE: Several cases of syndrome of inappropriate antidiuresis (SIAD) induced
      by antiparkinson agents have been reported. Our previous study demonstrated that
      in some patients with Parkinson's disease (PD), pergolide and pramipexole
      stimulate elevations of plasma arginine vasopressin (AVP) levels even at doses
      that are lower than the ordinary maintenance dose. Although mean plasma AVP
      levels are significantly higher in treated PD patients than in treatment-naive
      patients, neither disease severity nor levodopa/carbidopa dosage (range, 300/30
      850/85 mg) correlates with plasma AVP levels. However, the effects of
      levodopa/carbidopa monotherapy on plasma AVP levels in older patients remain
      unknown. To address this issue, a 14-day before-after study was conducted.
      METHODS: Subjects in this study were consecutive treatment-naive patients with a
      diagnosis of possible PD who visited our clinic from November 2008 to September
      2009. Patients had no conditions that could be associated with high plasma AVP
      levels. Twenty-five patients were treated with levodopa/carbidopa (100/10 mg) 3
      times a day. A paired t-test was used to compare plasma AVP levels before and 14
      days after initiation of treatment. RESULTS: Five patients dropped out of this
      study. In the remaining 20 patients (8 males and 12 females), no significant
      differences were observed between mean plasma AVP levels before and during
      treatment with levodopa/carbidopa. CONCLUSION: Monotherapy with
      levodopa/carbidopa (300/30 mg/day) does not affect plasma AVP levels in older PD
      patients and seems less likely to cause SIAD.

PMID- 22467110
TI  - Growth hormone (GH) peak after falling asleep reflects spontaneous nocturnal GH
      secretion, however is not corresponding to the results of GH stimulating tests in
      children with short stature.
AB  - OBJECTIVE: Growth hormone (GH) secretion is characterized by a pulsatile,
      circadian rhythm, with the highest concentrations at night hours. Evaluation of
      nocturnal GH secretion may be truncated to 6 hours. Growth hormone stimulating
      tests are the standard method of assessment of GH secretion. In Poland, the
      assessment of GH peak during 2 hours after falling asleep was introduced as a
      screening procedure in children, suspected for GH deficiency.  The aim of current
      study was to compare the results of a screening test with GH secretion during 6
      hour nocturnal profile and with the results of GH stimulating tests, as well as
      with IGF-I secretion in children with short stature. METHODS: In 72 short
      children, GH concentrations were measured every 30 minutes during first 6 hours
      after falling asleep and in two GH stimulating tests (the cut-off level of GH
      peak for all the tests was 10.0 ng/ml). Also, IGF-I concentrations were measured
      and expressed as IGF-I SDS for age and sex. RESULTS: The screening test results
      correlated significantly with both GH peak in 6-hour profile and mean GH
      concentration, and the area under the curve (AUC) in 6 hour profile (r= 0.94,
      r=0.90 and r=0.89, respectively, p<0.05) but not with GH peak in stimulating
      tests (r=0.07, NS). There was no correlation between IGF-I secretion and any of
      the analyzed parameters of spontaneous and stimulated GH secretion. CONCLUSIONS:
      The results of screening test seem to reflect overnight GH secretion in short
      children, remaining, however, discordant with the results of GH stimulating tests
      and with IGF-I secretion.

PMID- 22467111
TI  - Prevalence of hypothalamic-pituitary tumours - retrospective analysis of 20-year
      own material.
AB  - OBJECTIVES: The prevalence of pituitary tumours has recently been identified to
      be higher than previously thought. The aim of our study was to assess the
      occurrence of hypothalamic-pituitary tumours in 20-year material of the
      Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial
      Hospital - Research Institute, Lodz, Poland. METHODS: We analyzed medical data of
      845 patients, hospitalized from 1990 to 2009 due to presumptive diagnosis of
      hypothalamic-pituitary tumour. Among 340 cases with confirmed diagnosis, 278
      tumours were classified as micro- or macroadenomas. Tumour type and size, as well
      as patient gender and age, were evaluated. In 252 tumours the exact volume was
      calculated, and 4 volume subgroups were assessed for each aforementioned
      parameter separately. RESULTS: Prolactinomas and - at the next place - non
      functioning adenomas were the most frequent, followed by pituitary tumors of non
      epithelial origin, and - finally, the rarest - other secreting adenomas.
      Prolactinomas were found mostly in females (p=0.028), while non-functioning
      adenomas in males (p=0.045). Prolactinomas and non-functioning adenomas were
      found to be predominantly microadenomas (p<0.0001 and p=0.0003, respectively),
      while mixed-type adenomas were mostly macroadenomas (p=0.028). In females
      microadenomas were the most frequent (p<0.0001). Moreover, in persons under 50
      years of age microadenomas predominated, whereas in older adults macroadenomas
      mostly occurred. CONCLUSION: To conclude, our retrospective, single-centre study
      provides relevant estimates of prevalence of hypothalamic-pituitary tumours in
      the era of modern diagnostic tools and indicates that our data are comparable
      with results regarding other populations worldwide.

PMID- 22467112
TI  - An ADP-ribosyltransferase 3 (ART3) variant is associated with reduced sperm
      counts in Czech males: case/control association study replicating results from
      the Japanese population.
AB  - OBJECTIVES: In about 50% of male infertility the underlying pathogenesis remains
      unknown. A recent Japanese study provided evidence that the rs6836703: G>A single
      nucleotide polymorphism (SNP) from the ADP-ribosyltransferase 3 (ART3) gene is
      significantly associated with non-obstructive azoospermia. However, the
      functional significance of this association is unknown and replication studies in
      unrelated populations are thus necessary. DESIGN: In this study, 257 fertile
      Czech controls of proven paternity and 98 sub-/infertile patients selected
      according to stringent exclusion / inclusion criteria were genotyped by High
      Resolution Melting (HRM) of small amplicons. SETTING: This study was performed at
      University Hospital Motol - Laboratory of reproductive genetics using routinely
      analyzed cases. RESULTS: Significant differences in allele distribution between
      fertile and sub-/infertile men were found (OR=1.78, 95% CI: 1.17-2.70; p=0.007).
      Following sub-stratification of cases according to their sperm counts we found
      that observed differences in allele distributions were increased in
      oligozoospermic men with sperm counts of <15 million sperm/mL (OR=1.98, 95% CI:
      1.28-3.07; p=0.002). This difference was also reflected in genotype distributions
      between fertile and sub-/infertile men (p=0.008), and fertile versus
      oligozoospermic men (p=0.004). CONCLUSIONS: Our study serves as a first
      replication of the original Japanese report and opens new avenues of research.
      Compared to the Japanese patient cohort, we provided evidence that the analyzed
      ART3 variant is associated with quantitative impairment of spermatogenesis.

PMID- 22467113
TI  - A profile of the insulin receptor in cultured hippocampal slices.
AB  - OBJECTIVES: Insulin receptors (IRs) are distributed in a region-specific fashion
      throughout the brain, and may play a role in processes related to learning and
      memory. The hippocampus, which participates in spatial memory formation, is one
      region in which the IR is abundantly expressed. Organotypic hippocampal slice
      cultures (OHSCs) are an in vitro model that permits the easy manipulation of
      growth conditions, yet retains much of the source structure's cytoarchitecture.
      To assess OHSCs as a model for the study of hippocampal IRs, ligand-binding and
      the expression and cellular distribution of the beta-subunit (which transduces
      the insulin signal) were examined over time in culture.  Design & Results:
      Fluorescently conjugated insulin was used to assess neural insulin receptor
      binding, and revealed that labelling remained similar over three weeks in culture
      (a typical length of OHSC maintenance). Cross-linking of surface proteins helped
      to show that approximately half of beta-subunits were found at the cell surface,
      and that this relative proportion remained stable over several weeks. In
      contrast, expression of the beta-subunit protein progressively declined to a
      plateau approximately 60% less than that seen when the cultures were prepared.
      CONCLUSIONS: Our results provide a foundation for subsequent studies to employ
      OHSCs to explore neural IRs; for instance, the dissonance between the progressive
      decline in expression of the IR beta-subunit and the relative stability of
      receptor-mediated binding suggests the presence of an active process to hold
      steady the ability of cells to respond to insulin stimulation.

PMID- 22467114
TI  - Vasovagal (neurocardiogenic) syncope in the clinical practice.
AB  - OBJECTIVES: Vasovagal syncope (VVS) is the most common type of syncope with the
      incidence of 21-43%. The aim of this study was to explain difficulties of correct
      diagnosis of VVS. DESIGN AND METHODS: Our group comprises 70 patients (24 men, 46
      women) at the age of 15-71 years, in whom VVS was verified by the head-up tilt
      test (HUT-test). We evaluated the type of VVS, admission diagnoses present in the
      patients, interictal EEG findings and the presence of convulsions during the
      syncopal states. For statistical processing of the results we used binomial tests
      for two independent proportions, Fisher-Freeman-Haltons exact test and Cramer's V
      index. RESULTS: Out of 70 VVS 35 were vasodepressoric, 19 cardioinhibitive and 16
      intermediate. Admission diagnoses present in the patients were: disorders of
      consciousness of an unknown etiology - 42.9% cases; supposable epilepsy and
      epilepsy - 30% cases and syncope - 27.1% cases. Interictal EEG was normal in
      51.4% cases, nonepileptiform abnormality was present in 48.6% cases. Statistical
      comparison among particular types of VVS revealed a significant difference in
      distribution and medial strong association between the type of VVS and the EEG
      finding (Cramer V=0.35) and also between the type of VVS and the occurrence of
      convulsions (Cramer V= 0.40). CONCLUSION: The results of our study evidently
      suggest that interdisciplinary cooperation in accurate diagnostics in this field
      of medicine is needed and that HUT-test has to be in standard diagnostic
      algorithm in patients with failures of consciousness of an unknown cause.

PMID- 22467115
TI  - Physiotherapy as an immunoactive therapy?  A pilot study.
AB  - OBJECTIVES: The aim of this study was to confirm the immunoregulatory and anti
      inflammatory changes in the immunologic profile after two months of the
      facilitation physiotherapy in patients with multiple sclerosis; and to determine
      whether the changes in the immunologic profile correlate with the changes in
      dehydroepiandrosterone, the brain microstructure and clinical functions. DESIGN &
      SETTING: A group of 12 patients with multiple sclerosis was examined twice: at
      the beginning and 2 months later after the patients had undergone the
      facilitation therapy. Standardized tests evaluating chosen clinical functions
      (balance, righting, equilibrium and protective reactions, tremor,
      dysdiadochokinesis, dysmetry, fine hand function and walking), immune parameters
      (parameters of the humoral and cellular immunity), dehydroepiandrosterone and
      diffusion tensor imaging (the fractional anisotropy, mean diffusivity) were
      measured. The patients underwent the facilitation physiotherapy in two sessions
      lasting two hours each week for two months. RESULTS: All clinical and diffusion
      tensor imaging parameters significantly improved following the therapy. Without
      the correction for multiple comparisons, there were significant changes in the
      IgG, IgG1 subclasses, in the numbers of Neutrophils and Lymphocytes, the T cells
      (CD3+) absolute number, the T cytotoxic subpopulation (CD3+CD8+) absolute number,
      B cells (CD19+) and the Natural killer cells. In addition, there was a
      significant correlation between the changes in the clinical functions and the
      changes in IgG1 (r=0.67), and between the changes in the mean diffusivity and the
      changes in CD3+CD8+ absolute (r=-0.61). The changes in the immune parameters and
      the mentioned correlations were not significant in view of the number of
      comparisons and thus necessitate further validation. No changes in the
      dehydroepiandrosterone concentration after the therapy were confirmed.
      CONCLUSION: The study suggests new possibilities of physiotherapy to influence
      the psycho-neuro-endocrine-immune response in patients with multiple sclerosis.

PMID- 22467116
TI  - Is screening for hereditary thrombophilia indicated in first early pregnancy
      loss?
AB  - OBJECTIVE: The aim of the study was to evaluate the importance of screening for
      thrombophilic mutations after the first early pregnancy loss. SETTING:
      Thrombophilic mutations were examined in a sample of 100 women with at least one
      miscarriage. DNA was isolated from venous blood sample. We used methods of
      microarray, fragmentation analysis, High Resolution Melting and PCR-ARMS with
      following gel electrophoresis and visualisation. Chi-square test and in cases of
      low expected frequencies Yates correction were used to compare relative
      frequencies of individual mutations. The comparison of averages was performed by
      t-test. RESULTS: We detected prevalence of factor V and II mutation of 9% and 3%,
      respectively. Single MTHFR mutation was found in 59% and double heterozygous
      MTHFR mutation in 23% of cases. No mutation was present in only 6% of the study
      group. Heterozygous mutations of factor V occurred 1.8 times more frequently in
      our study group compared to the general Czech women population. Also, the
      frequency of factor II mutation was 1.5-3 times higher. No carrier of these
      mutations had overt coagulation disorder, history of thromboembolic disease or
      that of habitual abortions. CONCLUSIONS: The frequency of thrombophilic mutations
      in the group of women with early pregnancy loss is 1.5-3 times higher than in the
      general population.

PMID- 22467117
TI  - The concentration of blood pressure regulating hormones in premenopausal women
      with isolated systolic hypertension related to hyperthyroidism.
AB  - OBJECTIVE: The aim of the study was to establish the concentration of blood
      pressure regulating hormones in premenopausal women with isolated systolic
      hypertension (ISH) related to hyperthyroidism (HT). MATERIAL AND METHODS: 61
      females with HT were enrolled in the study, including 28 with ISH (Group A), 33
      with normal arterial blood pressure (Group B) and 34 healthy individuals (Group
      C). It was determined - plasma renin activity (PRA), plasma concentration of
      arginine vasopressin (AVP), atrial natriuretic hormone (ANH) and aldosterone
      (Aldo). PRA and Aldo tests were performed twice, firstly under basal conditions
      and then after a 3-day low-sodium diet. In hyperthyroid patients tests were
      repeated during thyreostatic treatment. Patients with sodium-sensitivity of blood
      pressure were selected. Cardiac index (CI) and total peripheral resistance index
      (TPRI) were calculated. RESULTS: In ISH patients the basal PRA was lower than in
      patients of Groups B and C. The highest poststimulatory PRA was observed in
      patients of Group B. ANH concentration was higher in both HT groups compared to
      the Group C. AVP concentration in ISH patients was higher than in Group C. In HT
      patients blood pressure correlated with basal PRA, CI and TPRI. Sodium
      sensitivity of blood pressure was observed more frequently in patients from Group
      A. CONCLUSIONS: In women, ISH in HT is the consequence of the increased cardiac
      output and the decreased peripheral vascular resistance. ISH related to HT
      results in the reduction in basal PRA probably as the result of intensified
      cardiac ejection function. ISH in hyperthyroid patients shows a higher sodium
      sensitivity.

PMID- 22467118
TI  - Does repetitive transcranial magnetic stimulation have a positive effect on
      working memory and neuronal activation in treatment of negative symptoms of
      schizophrenia?
AB  - OBJECTIVE: The objective of the study was to find out whether, under the
      conditions of a double-blind, placebo coil controlled study, high-frequency
      repetitive transcranial magnetic stimulation (TMS) over the left prefrontal
      cortex will show positive effects on working memory with simultaneous assessment
      of respective changes in neuronal activation. RESULTS: Stimulation treatment led
      to a reduction of seriousness of negative schizophrenia symptoms in both
      comparative groups. However, mutual comparison of real (n=19) and sham (n=11)
      rTMS, respectively, has shown that the effect of real rTMS was statistically
      significantly higher compared with placebo stimulation. During stimulation
      treatment an improvement in working memory performance was also found. No
      statistically significant difference between the real and placebo sham rTMS,
      respectively, was established. The rate of neuronal activation did not change at
      all during rTMS treatment. CONCLUSIONS: From clinical point of view rTMS seems to
      be a well-tolerated neurostimulation method for treatment of negative
      schizophrenia symptoms with favourable of impact on cognitive functions.

PMID- 22467119
TI  - Delayed delivery of a twin - a hazard or an acceptable method? Prospective study.
AB  - OBJECTIVE: To examine the possibility of postponement of the delivery of fetus B
      after preterm delivery or late abortion of fetus A in multiple pregnancy.
      METHODS: Between January 2000 and September 2010, we tried to delay delivery of
      the second twin in 18 cases. Group A includes women that experienced a preterm
      premature rupture of the membranes in fetus A (PPROM), group B includes women who
      presented with regular uterine activity and the vaginal finding indicated
      unavoidable late miscarriage or preterm delivery. RESULTS: Thirteen (72.22%) of
      the 18 attempts were evaluated as unsuccessful. The interval of delay of delivery
      of fetus B ranged between 24 and 384 hours. Five cases were successful.
      CONCLUSION: Indication for applying this therapeutic procedure to a pregnant
      woman must be strictly selective. The procedure will be also in future more or
      less reserved for women in which subsequent pregnancy is for different reasons
      highly improbable.

PMID- 22467120
TI  - Is proximal femoral nailing a good procedure for teaching in orthogeriatrics?
AB  - BACKGROUND: Proximal femoral nailing is a common operation in orthogeriatrics and
      a highly standardized procedure. For teaching purposes, this operation is often
      performed by residents and supervised by attending physicians. The objective of
      this study is to investigate if teaching this operation influences the surgical
      in-house complication rate. PATIENTS AND METHODS: All patients who received a
      proximal femoral Targon PF nail (Aesculap AG, Tuttlingen, Germany) for
      trochanteric fractures were included in a cohort at our urban academic teaching
      hospital between 1998 and 2010. To evaluate potential effects of patient age, we
      separately analyzed several age groups. Complications including wound infection,
      hematoma, intraoperative malreduction or implant malpositioning causing revision,
      pain, cut-out and readmission due to nonunion were recorded. RESULTS: Our
      collective consists of 1,516 patients (m/f: 410/1,106). The mean age was 78.7
      years (range: 19-103 years). The overall complication rate was 7.9 %. In 857
      cases operated by attending physicians, the complication rate was 6.9 %. However
      in the 659 operations performed by residents, we found a higher complication rate
      of 9.3 %. Further investigating this difference by chi(2) test, we found no
      significance (p = 0.09). Whilst analyzing the complication rates for the
      different age groups, we did not find a statistically significant difference
      except in the age group between 71 and 80 years, for which the odds ratio
      indicated a 2.6-fold increased complication risk for operations performed by
      residents (p = 0.01). Further analysis revealed that this increased complication
      rate was mainly due to increased numbers of cut-out. CONCLUSION: We conclude that
      proximal femoral nailing is an operation suitable for teaching purposes. However,
      patients between 71 and 80 years of age seem to be at an increased risk for cut
      out if operated by a resident.

PMID- 22467121
TI  - Janus Au-TiO2 photocatalysts with strong localization of plasmonic near-fields
      for efficient visible-light hydrogen generation.
AB  - The first use of non-centrosymmetric Janus Au-TiO(2)  photocatalysts in
      efficient, plasmon-enhanced visible-light hydrogen generation is demonstrated.
      The intense localization of plasmonic near-fields close to the Au-TiO(2) 
      interface, coupled with optical transitions involving localized electronic states
      in amorphous TiO(2)  brings about enhanced optical absorption and the generation
      of electron-hole pairs for photocatalysis.

PMID- 22467122
TI  - A collection of popcorn as a reservoir of genes for the generation of lineages.
AB  - In the present study, we analyze the genetic structure and diversity among
      accessions of popcorn obtained from the CIMMYT International Maize and Wheat
      Improvement Center that represent the diversity available for current use by
      breeding programs. The main objectives were to identify SSR loci that were the
      best indicators of genetic diversity, to measure the genetic diversity within
      popcorn genotypes, and to analyze the genetic structure of the promising
      populations destined for use in breeding programs. The mean gene diversity of all
      SSR loci was 0.6352. An extremely high population differentiation level was
      detected (F(st) = 0.3152) with F(st) for each locus ranging from 0.1125 (Umc1229)
      to 0.4870 (Umc1755). Analyzing the genetic structure of eight popcorn accessions
      was especially important for identifying both SSR loci with high levels of
      heterozygosity and genotypes showing high heterozygosity (BOYA462 and ARZM13
      050). This analysis should be the medium and long-term selection goal for the
      generation of inbred lines and the future production of new cultivars. Plant
      accessions ARZM05 083, ARZM13 050, and URUG298 may also be useful varieties that
      exhibit important agronomic characteristics that can be used through crosses to
      broaden the genetic basis of popcorn.

PMID- 22467124
TI  - Suggestions from the field for return-to-sport rehabilitation following anterior
      cruciate ligament reconstruction: alpine skiing.
AB  - Alpine skiing is a high-risk sport for injuries to the anterior cruciate ligament
      (ACL). While descending a hill, a skier must resist large centrifugal forces at a
      high velocity, while the knees are positioned in postures that place the ACL at
      risk of injury. Skiers who undergo ACL reconstructive surgery are prone to a high
      rate of reinjury to the same knee and even ACL injury in the uninjured knee. A
      rehabilitation program that integrates the best current evidence of ACL
      rehabilitation and the science of skiing is essential to a successful return to
      alpine skiing. Unlike rehabilitation programs developed for court or field
      athletes, a skiing program must place a large emphasis on slow eccentric-loading
      and weight-bearing (closed-chain) power and endurance. The purpose of this
      clinical commentary is to provide the rehabilitation specialist such a program
      directed toward safely returning the athlete to alpine skiing.

PMID- 22467123
TI  - Performance of high quality minicircle DNA for in vitro and in vivo gene
      transfer.
AB  - Plasmid DNA is frequently used particularly for nonviral gene therapy.
      Conventional plasmid DNA contains bacterial backbone and resistance gene
      sequences, as well as immunogenic CpG motifs. These components are not required
      for transgene expression. They represent a potential risk for safe clinical
      application and reduce gene transfer rates as well as transgene expression. To
      overcome these drawbacks, the minicircle technology is removing such sequences,
      to improve performance and also to reduce DNA size. Here, we show the effective
      production of luciferase, GFP, or lacZ-carrying minicircle DNA with high yield
      and reproducible high quality. They are used for lipofection or electroporation
      gene transfer into human melanoma and colon carcinoma cell lines. Comparison of
      respective parental plasmid and minicircle-mediated luciferase gene transfer
      shows improved luciferase expression by minicircle in all cell lines. This is not
      associated with increase in intracellular minicircle copy numbers after
      lipofection or electroporation. The minicircles rather mediate enhanced transgene
      mRNA transcription compared to their parental plasmids. In addition, FACS
      analysis revealed increase in counts of GFP positive cells after minicircle gene
      transfer, indicating higher gene transfer rates. Furthermore, minicircle showed
      also improved performance in vivo after jet-injection gene transfer. Therefore,
      availability of minicircles with reproducible high quality and sufficient amount
      makes them an applicable and effective alternative to conventional plasmid gene
      vectors.

PMID- 22467125
TI  - [Malassezia infections].
AB  - Although Malassezia yeasts are a part of the normal microflora, under certain
      conditions they can cause superficial skin infection Pityriasis versicolor,
      Malassezia folliculitis. Lipophilic yeasts are being considered as major
      opportunistic pathogens for a very long time. Most of the yeasts show an absolute
      requirement for long fatty acid chains and specific procedures are required for
      their isolation, conservation and identification. To date, the genus is composed
      of one non lipid-dependent species M. pachydermatis and lipid-dependent species
      M. furfur, M. sympodialis, M. globosa, M. obtusa, M. restricta, M. slooffiae, M.
      dermatis, M. yamatoensis, M. japonica, M. nana, M. caprae, M. equina, M.
      cuniculi.

PMID- 22467126
TI  - [Pneumocystis infections].

PMID- 22467127
TI  - [Cutaneous mycoses in Japan originating from animals].
AB  - Human cases of dermatophytoses are occasionally transmitted from animals, and
      suffered from tinea corporis and sometimes Kerion celsi. The most frequent
      causative agent of these diseases is Microsporum canis. The other dermatophyte,
      Arthroderma benhamiae is now prevailing in rabbits, rodents and hedgehogs that
      are popular household pets in Japan. Therefore, some human cases of A. benhamiae
      infection were reported and the transmission of this infection from rabbits and
      rodents was confirmed.Cryptococcosis is regarded as dangerous zoonosis, but its
      transmission from animal to peoples has not been documented in Japan. Animal
      cases of cryptococcosis are possible to increase in number by developing
      immunosuppressive animals as well as by spreading of newly introduced C. gattii
      to Japan.Animal cases of sporotrichosis are rarely reported in Japan. However,
      feline sporotrichosis should be prevented and promptly treated since it easily
      transmitted to people from cat lesions and the exudates where copious numbers of
      organisms are found in tissues.

PMID- 22467128
TI  - [Negative regulatory factor of CAWS (Candida albicans water-soluble fraction) 
      vasculitis in CBA/J mice as assessed by comparison with Bruton's tyrosine kinase
      deficient CBA/N mice].
AB  - Candida albicans water-soluble fraction (CAWS) has microbial pathogen-associated
      molecular patterns (PAMPs). It is a mannoprotein-beta glucan complex obtained
      from the culture supernatant of Candida albicans NBRC1385 and exhibits vasculitis
      inducing activity (CAWS vasculitis) in mice. The sensitivity to CAWS vasculitis
      varies greatly among mouse strains. This study examined the factors contributing
      to or inhibiting CAWS vasculitis using CAWS-vasculitis-resistant CBA/J mice and
      Bruton's tyrosine kinase (Btk)-deficient CBA/N mice, which is a CAWS-vasculitis
      sensitive strain having the same origin as CBA/J mice. After stimulation with
      various kinds of pathogen-associated molecular patterns (PAMPs), the production
      of inflammatory cytokines IL-6 and IFN-gammawas induced in CBA/N mice, whereas
      that of immunosuppressive IL-10 was induced in CAWS-vasculitis-resistant CBA/J
      mice. The production of TIMP1, an endogenous matrix metalloproteinase (MMP)
      inhibitor, was observed in CBA/J mice. Furthermore, the induction of CAWS
      vasculitis was inhibited by gene therapy using plasmid (pCAGGS-mIL-10).  The
      results strongly suggest that the difference in the production of these cytokines
      is closely linked to the development of CAWS vasculitis.

PMID- 22467129
TI  - [Inhibitory activity of hydrosols prepared from 18 Japanese herbs of weak
      aromatic flavor against filamentous formation and growth of Candida albicans].
AB  - Leaf hydrosols prepared from 18 weakly aromatic Japanese herbs used traditionally
      were tested on the filamentation-inhibitory activity of Candida albicans. These
      hydrosols were divided into two classes, A and B. The inhibitory activity of 13
      hydrosols belonging to class A was markedly altered depending on the drying
      process of the parent herbs. On the other hand, the remaining 5 hydrosols
      belonging to class B showed no significant change on the composition and
      inhibitory activity upon drying. The change of the bioactivity was correlated
      with the change and concentration of the respective major constituents.
      Especially strong bioactivity shown by hydrosols of dried Houttuynia cordata and
      fresh Prunus pendula was ascribed to n-capric acid and cyanide, respectively.
      Eight hydrosols exhibited weak or moderate activity against the growth of C.
      albicans.

PMID- 22467130
TI  - [Effect of oral administration of beta-D-glucan from Aureobasidium pullulans ADK
      34 on Candida and MRSA infections in immunosuppressed mice].
AB  - We examined the effect of the oral administration of beta-D-glucan derived from
      Aureobasidium pullulans ADK-34 (AP-FBG) on Candida albicans or methicillin
      resistant Staphylococcus aureus (MRSA) infection in immunosuppressed mice. Mice
      pretreated with cyclophosphamide (CY) were intraperitoneally administered AP-FBG
      for 4 days and then infected with 6*10(4) C. albicans cells. In a preliminary
      experiment, the survival time of the Candida-infected mice treated with AP-FBG
      was clearly prolonged. Similarly, the effect of the oral administration of AP-FBG
      was examined. Mice were orally given 2.5% AP-FBG in feed for 42 days from 14 days
      prior to 2*10(4) C. albicans cells infection. The survival time of mice treated
      with AP-FBG was significantly prolonged and the viable cell count in the kidneys
      of the survivors was significantly decreased at 30 days after infection. The
      effects of the oral administration of AP-FBG on intestinal MRSA infection were
      also examined. Mice were given 2.5% AP-FBG orally in feed for 30 days before and
      after oral MRSA infection and treated with CY 12 days after the infection. The
      number of viable MRSA cells or the IgA production in feces did not significantly
      change, while AP-FBG administration seemed to relieve temporally the loss of body
      weight of mice. CONCLUSIONS: These results suggest that oral pre-administration
      of AP-FBG promoted resistance of CY-treated mice to C. albicans and lessened the
      weight reduction of CY-mice infected by MRSA.

PMID- 22467131
TI  - [Case of oral paracoccidioidomycosis suspected to be pharyngeal cancer].
AB  - Paracoccidioidomycosis is a fungal infection endemic to South American countries
      that affects the lungs, skin, and mucosae. Reports from Japan are limited by a
      long-term resident in South America. Some cases are incorrectly diagnosed because
      of a refractory buccal ulcer that resembles a malignant tumor. This is a disease
      that may not be correctly examined if we cannot suspect by a case history. We
      report the case of a Brazilian man who had a buccal ulcer with lung involvement,
      which mimicked pharyngeal cancer.

PMID- 22467132
TI  - [Estimated numbers of visceral mycoses in cases of leukemia and MDS in Japan :
      analysis of data from the Annual of Pathological Autopsy Cases and the vital
      statistics published by Ministry of health, labour and welfare in Japan].
AB  - Our analysis reported here, is the first one in the world to make a nationwide
      level estimate on numbers of visceral mycoses in case of leukemia and
      myelodysplastic syndrome (MDS)in Japan. The data on visceral mycoses in cases
      reported in the" Annual of the Pathological Autopsy Cases in Japan" published by
      the Japanese society of pathology in 2002 and 2006, and the data in the vital
      statics in Japan published by Ministry of health, labour and welfare were
      analyzed epidemiologically. The estimated numbers of visceral mycoses were 2,250
      out of the estimated total death 8,976 in 2001, and 2290 out of 9,805 in 2005,
      respectively, in cases of leukemia and MDS in Japan. Furthermore, the estimated
      severe cases that we thought direct cause of death were 1,454 in 2001, and 1,464
      in 2005, respectively. In the severe cases, the most causative agents were
      Aspergillus. The estimated numbers of Candida and Zygomycetes were interestingly
      almost same in the severe cases, but the lethal rate in Zygomycetes was about 60
      80 % , almost twice as that in Candida. We think it is imperative to continuously
      survey and watch these rates towards the future.

PMID- 22467133
TI  - Root herbivore effects on aboveground multitrophic interactions: patterns,
      processes and mechanisms.
AB  - In terrestrial food webs, the study of multitrophic interactions traditionally
      has focused on organisms that share a common domain, mainly above ground. In the
      last two decades, it has become clear that to further understand multitrophic
      interactions, the barrier between the belowground and aboveground domains has to
      be crossed. Belowground organisms that are intimately associated with the roots
      of terrestrial plants can influence the levels of primary and secondary chemistry
      and biomass of aboveground plant parts. These changes, in turn, influence the
      growth, development, and survival of aboveground insect herbivores. The discovery
      that soil organisms, which are usually out of sight and out of mind, can affect
      plant-herbivore interactions aboveground raised the question if and how higher
      trophic level organisms, such as carnivores, could be influenced. At present, the
      study of above-belowground interactions is evolving from interactions between
      organisms directly associated with the plant roots and shoots (e.g., root feeders
      - plant - foliar herbivores) to interactions involving members of higher trophic
      levels (e.g., parasitoids), as well as non-herbivorous organisms (e.g.,
      decomposers, symbiotic plant mutualists, and pollinators). This multitrophic
      approach linking above- and belowground food webs aims at addressing interactions
      between plants, herbivores, and carnivores in a more realistic community setting.
      The ultimate goal is to understand the ecology and evolution of species in
      communities and, ultimately how community interactions contribute to the
      functioning of terrestrial ecosystems. Here, we summarize studies on the effects
      of root feeders on aboveground insect herbivores and parasitoids and discuss if
      there are common trends. We discuss the mechanisms that have been reported to
      mediate these effects, from changes in concentrations of plant nutritional
      quality and secondary chemistry to defense signaling. Finally, we discuss how the
      traditional framework of fixed paired combinations of root- and shoot-related
      organisms feeding on a common plant can be transformed into a more dynamic and
      realistic framework that incorporates community variation in species, densities,
      space and time, in order to gain further insight in this exciting and rapidly
      developing field.

PMID- 22467136
TI  - Kineococcus glutineturens sp. nov., isolated from soil in Yunnan, south-west
      China.
AB  - An orange-coloured, non-spore-forming, motile and coccus-shaped actinobacterium,
      designated YIM 75677(T), was isolated from a soil sample collected from a dry-hot
      river valley in Dongchuan county, Yunnan Province, south-west China and its
      taxonomic position was investigated. Growth of strain YIM 75677(T) occurred at 12
      55  degrees C, pH 6.0-9.0 and NaCl tolerance up to 2 % (w/v). Cells adhered to
      agar media and were agglutinated tightly together. The peptidoglycan contained
      meso-diaminopimelic acid, alanine and glutamic acid. The whole-cell hydrolysates
      mainly contained glucose, galactose, mannose and ribose. The predominant
      menaquinone was MK-9 (H(2)) and the major fatty acids were anteiso-C(15:0) and
      iso-C(15:0). Mycolic acids were not present. The DNA G+C content of strain YIM
      75677(T) was 74.8 mol%. Phylogenetic analyses based on 16S rRNA gene sequence
      comparisons clearly revealed that strain YIM 75677(T) represents a novel member
      of the genus Kineococcus and is closely related to Kineococcus xinjiangensis S2
      20(T) (level of similarity, 98.6 %). Meanwhile, the result of DNA-DNA
      hybridization between strain YIM 75677(T) and K. xinjiangensis S2-20(T)
      demonstrated that this isolate represented a different genomic species in the
      genus Kineococcus. On the basis of phylogenetic, phenotypic and chemotaxonomic
      characteristics, strain YIM 75677(T) represents a novel species of the genus
      Kineococcus, for which the name Kineococcus glutineturens sp. nov. is proposed.
      The type strain is YIM 75677(T) (=CCTCC AA 209075(T) = JCM 18126(T)).

PMID- 22467137
TI  - Evaluation of renal biopsies in type 2 diabetic patients with kidney disease: a
      clinicopathological study of 216 cases.
AB  - OBJECTIVES: The outcome and the therapy of patients with diabetes mellitus (DM),
      diabetic nephropathy (DN), and non-diabetic renal disease (NDRD) are quite
      different, so the differential diagnosis is of considerable importance. To
      evaluate the usefulness of renal biopsy in type 2 diabetic patients, we examined
      the relationship between the clinical parameters and the histopathological
      findings in different age groups. METHODS: Renal biopsy specimens and clinical
      and laboratory data from 216 patients with type 2 DM were evaluated. According to
      their age, three groups were defined: 17-35 years (group I), 36-59 years (group
      II), and more than 60 years (group III). RESULTS: The study showed that, beside
      the duration of diabetes, other clinical parameters were not significantly
      different between the three groups. Chronic nephritic syndrome was the most
      common clinical manifestation in group I (44.1 %) and in group II (34.0 %). Among
      patients in group III, we found a high prevalence of chronic renal failure (34.3
      %) and nephrotic syndrome (28.6 %). Consistent with the clinical manifestations,
      IgA nephropathy was the most common pathologic finding in group I (29.4 %) and in
      group II (34.7 %), whereas the most frequent abnormalities in group III were
      membranous nephropathy (25.7 %) and tubulointerstitial lesions (14.3 %). Overall,
      among these patients, 14 cases were diagnosed with DN (6.5 %), 179 with NDRD
      (82.9 %), while 23 had concurrent DN and NDRD (10.7 %). CONCLUSIONS: Our results
      indicated that the clinical manifestations and pathologic findings in type 2
      diabetic patients in different age groups have different features. This study
      emphasized the usefulness of renal biopsy for determining the pattern of renal
      damage and thus for the overall management of type 2 diabetic patients.

PMID- 22467138
TI  - Identifying the palliative care needs of patients living with cerebral tumors and
      metastases: a retrospective analysis.
AB  - Primary tumors and metastatic involvement of the central nervous system (CNS)
      lead to a multitude of symptoms and care needs. Patients and caregivers struggle
      with physical and psychological impairments, a shortened life expectancy and
      diverse palliative care needs. This study assesses the symptom burden and
      palliative care needs of patients with primary brain tumors and with metastatic
      brain tumors requiring inpatient hospital care. It is a retrospective analysis of
      patients with primary CNS tumors or cerebral metastases over a 6 month period.
      The data analysed included physical symptom burden and end of life care decisions
      such as health care proxy, transition to hospice and do-not-resuscitate orders.
      Hundred and sixty eight patients were included. The most common symptoms were
      gait impairment (65.5 %), cognitive/personality change (61.9 %), motor deficits
      (58.3 %), seizures (57.1 %) and delirium (27.4 %). Of the patients that died, 79
      % had an appointed health care proxy, 79 % had hospice discussions, 70 % had a do
      not-resuscitate order and 24 % received cancer directed therapy in the last month
      of life. There is a role for more aggressive palliative care support in patients
      living with primary or metastatic brain tumors.

PMID- 22467140
TI  - Retraction of article: Stable chloroplast transformation of immature scutella and
      inflorescences in wheat (Triticum aestivum L.).

PMID- 22467139
TI  - Establishing a cancer cell in the inflammatory tissue: an epigenetic circuit.

PMID- 22467141
TI  - The relationship between time to surgical debridement and incidence of infection
      in grade III open fractures.
AB  - OBJECTIVE: The purpose of this study was to determine the association between
      time to initial debridement and infection rate in high-energy (grade III) open
      fractures of tibia. METHODS: All patients presenting with open fractures were
      included in the study. The inclusion criteria were Gustilo III A, B and C open
      fractures of tibia. Time of injury, time of arrival to the hospital, time of
      initial debridement and subsequent soft tissue procedures were recorded. The
      primary outcome measure was a diagnosis of infection or osteomyelitis at 1 year.
      Secondary outcome measure was fracture union at 1 year. RESULTS: Sixty-seven (67)
      patients with grade III open fractures were included; the mean age was 32.4 years
      (54 males and 13 females). Eight patients (12 %) in this study went on to develop
      a deep infection, and there were 6 (8.4 %) non-unions. The infection rate for
      patients in the group who underwent debridement in less than 6 h and those
      greater than 6 h was 13.1 and 10.8 %, respectively. No statistically significant
      difference could be demonstrated between the two groups (p = 0.56). While there
      was no significant relationship between grade of fracture and infection rate (p =
      0.07), the relationship between grade of fracture and non-union was significant
      (p = 0.02). CONCLUSION: Our study shows that the risk of developing an infection
      was not increased if the primary surgical management was delayed more than 6 h
      after injury. Therefore, reasonable delays in surgical treatment for patients
      with open fractures may be justified in order to provide an optimal operating
      environment.

PMID- 22467142
TI  - Outcomes and complications of fibular head resection.
AB  - The fibular head is often used as donor graft material for reconstruction of
      defects of the distal radius. However little is known on the safety of such a
      procedure. This report describes the long-term donor-site morbidity following the
      procedure. Fourteen patients who underwent simple or marginal resections of the
      proximal fibula between 1990 and 2007 were reviewed. Subjective donor-site
      morbidity, knee and ankle range of motion and instability, presence of sensory or
      motor function loss, gait and fibular regeneration were assessed. The mean age at
      surgery was 25 years; six were male, eight were female and the mean follow-up was
      11 years. Abnormal clinical findings were present in 10 patients (71.4 %): nine
      patients (64.3 %) had Grade 2 varus laxity at the knee confirmed by stress
      radiographs; one had sensory loss in the distribution of the superficial peroneal
      nerve. Patients with varus laxity had significantly higher mean age at surgery
      than those without varus laxity (p = 0.001). None had deformity at the knee or
      ankle. The range of joint movements was normal. All had a normal tibiotalar angle
      and none had proximal migration of the fibula. One patient demonstrated near
      complete regeneration of the fibula. Donor-site morbidity following simple and
      marginal resection of the proximal fibula is acceptable. Older patients had a
      higher risk of demonstrable varus laxity at the knee but proximal fibula
      resection in children appears to be safe.

PMID- 22467143
TI  - Accounting for indirect land-use change in the life cycle assessment of biofuel
      supply chains.
AB  - The expansion of land used for crop production causes variable direct and
      indirect greenhouse gas emissions, and other economic, social and environmental
      effects. We analyse the use of life cycle analysis (LCA) for estimating the
      carbon intensity of biofuel production from indirect land-use change (ILUC). Two
      approaches are critiqued: direct, attributional life cycle analysis and
      consequential life cycle analysis (CLCA). A proposed hybrid 'combined model' of
      the two approaches for ILUC analysis relies on first defining the system boundary
      of the resulting full LCA. Choices are then made as to the modelling methodology
      (economic equilibrium or cause-effect), data inputs, land area analysis, carbon
      stock accounting and uncertainty analysis to be included. We conclude that CLCA
      is applicable for estimating the historic emissions from ILUC, although
      improvements to the hybrid approach proposed, coupled with regular updating, are
      required, and uncertainly values must be adequately represented; however, the
      scope and the depth of the expansion of the system boundaries required for CLCA
      remain controversial. In addition, robust prediction, monitoring and accounting
      frameworks for the dynamic and highly uncertain nature of future crop yields and
      the effectiveness of policies to reduce deforestation and encourage afforestation
      remain elusive. Finally, establishing compatible and comparable accounting
      frameworks for ILUC between the USA, the European Union, South East Asia, Africa,
      Brazil and other major biofuel trading blocs is urgently needed if substantial
      distortions between these markets, which would reduce its application in policy
      outcomes, are to be avoided.

PMID- 22467144
TI  - Biography of Stuart Lindsay.

PMID- 22467145
TI  - Vena cava thrombectomy during orthotopic liver transplantation without a
      venovenous bypass.

PMID- 22467147
TI  - Hormonal contraception and depression: a survey of the present state of
      knowledge.
AB  - PURPOSE: Depressive symptoms often occur among women of reproductive age. In this
      article we perform an analysis of existing studies to examine a possible
      correlation between depression and the use of hormone-based contraceptives.
      METHODS: The computerized databases MEDLINE/PubMed were searched for studies
      examining the relation between depressive disorders and hormonal contraception of
      the years 1976-2010. RESULTS: Data on this topic are limited. At least two
      confounding variables influence the analysis of the available data and make it
      difficult to draw firm conclusions: the inconsistent use of the term "depression"
      and the large number of combined contraceptives which vary in their composition.
      The association between the use of oral contraceptives and depression is not
      clear. We found that depression is not a common side effect of hormone-based
      contraceptives. CONCLUSION: Individual, patient-based decisions with
      consideration of the individual history and predispositions are recommended when
      starting oral contraceptives. If depressive symptoms or mood changes occur,
      decisions regarding discontinuation or medication change need to be made on an
      individual basis.

PMID- 22467146
TI  - Immune markers and differential signaling networks in ulcerative colitis and
      Crohn's disease.
AB  - BACKGROUND: Cytokine signaling pathways play a central role in the pathogenesis
      of inflammatory bowel disease (IBD). Ulcerative colitis (UC) and Crohn's disease
      (CD) have unique as well as overlapping phenotypes, susceptibility genes, and
      gene expression profiles. This study aimed to delineate patterns within cytokine
      signaling pathways in colonic mucosa of UC and CD patients, explore molecular
      diagnostic markers, and identify novel immune mediators in IBD pathogenesis.
      METHODS: We quantified 70 selected immune genes that are important in IBD
      signaling from formalin-fixed, paraffin-embedded (FFPE) colon biopsy samples from
      normal control subjects and UC and CD patients having either severe colitis or
      quiescent disease (n = 98 subjects). We utilized and validated a new modified
      real-time reverse-transcription polymerase chain reaction (RT-PCR) technique for
      gene quantification. RESULTS: Expression levels of signaling molecules including
      IL-6/10/12/13/17/23/33, STAT1/3/6, T-bet, GATA3, Foxp3, SOCS1/3, and downstream
      inflammatory mediators such as chemokines CCL-2/11/17/20, oxidative stress
      inducers, proteases, and mucosal genes were differentially regulated between UC
      and CD and between active and quiescent disease. We also document the possible
      role of novel genes in IBD, including SHP-1, IRF-1,TARC, Eotaxin, NOX2, arginase
      I, and ADAM 8. CONCLUSIONS: This comprehensive approach to quantifying gene
      expression provides insights into the pathogenesis of IBD by elucidating distinct
      immune signaling networks in CD and UC. Furthermore, this is the first study
      demonstrating that gene expression profiling in FFPE colon biopsies might be a
      practical and effective tool in the diagnosis and prognosis of IBD and may help
      identify molecular markers that can predict and monitor response to
      individualized therapeutic treatments.

PMID- 22467149
TI  - Work-related repetitive strain injuries amongst practitioners of obstetric and
      gynaecological ultrasound worldwide.
AB  - OBJECTIVES: The aims of this study were to determine the prevalence of work
      related musculoskeletal disorders amongst practitioners of obstetric and
      gynaecology ultrasound worldwide, and to establish relevant aetiological factors.
      METHODS: A questionnaire survey was conducted amongst the participants at the
      2010 ISUOG world congress held in Prague, Czech Republic. All pain complaints
      were evaluated in relation to the gender, operator experience, average workload
      and the background prevalence of obesity in the patient population scanned. Joint
      (neck, shoulder, elbow, wrist) or back pain was considered as repetitive strain
      injury (RSI). RESULTS: The response rate obtained was 49 %, with 407
      questionnaires returned out of a total of 830. Female operators reported more RSI
      than their male counterparts (70.1 vs. 59.6 %, p = 0.03). We found no significant
      relationship between the grade of the operator, the number of years of scanning
      experience, orientation in ergonomics and the occurrence of symptoms. Rest breaks
      in between cases revealed positive benefit (61.4 % RSI with rest vs. 71 % without
      rest, p = 0.041). The incidence of the reported RSI in the practitioners who had
      less than 30 % of their population classified as obese (body mass index of 30 or
      more) when compared with those who had more than 30 % of their case load
      classified as obese, was similar (65.3 vs. 64 %, p = 0.83). CONCLUSIONS: Operator
      dependant factors except gender, had little correlation with symptoms suffered,
      whilst the number of days worked per week, not taking regular breaks each day,
      revealed positive correlation. The results suggest that symptoms are both
      operator and workplace dependent. Though 65.6 % respondents suffered from RSI,
      less than half (30.5 %) resorted to supportive measures like physiotherapy.

PMID- 22467148
TI  - Comparison of tissue effects quantified histologically between PlasmaJet
      coagulator and Helica thermal coagulator.
AB  - INTRODUCTION: The PlasmaJet (PJ) coagulator uses neutral pure argon plasma to
      achieve coagulation. Helica thermal coagulator (HTC) achieves coagulation with
      helium gas. HTC is currently used in the treatment of mild to moderate
      endometriosis. OBJECTIVE: The objective of this study was to compare the tissue
      damage caused by PJ to the HTC in the uterus, ovary and fallopian tube. Our
      hypothesis was that PJ is a safe technology to use and the tissue damage caused
      is comparable to HTC. METHODS: Fifteen subjects undergoing hysterectomy with or
      without salpingo-oophorectomy were prospectively recruited for in vivo assessment
      of the two instruments. Both instruments were used on a small area of uterus,
      ovary and fallopian tube following the ligation of uterine artery pedicle. PJ was
      used at a power setting of 20 % for duration of 5 s at a clinically acceptable
      distance of 0.5 to 1 cm from the tissue surface. HTC was used at a widely
      accepted low power setting in the treatment of endometriosis for a similar
      duration and distance. Tissue damage was evaluated histologically. ANOVA was used
      to compare the mean differences. RESULTS: Data were normally distributed. Five
      subjects had a subtotal hysterectomy and 10 had hysterectomy with salpingo
      oophorectomy. A total of 15 uteri, 10 ovaries and 10 fallopian tubes were
      histologically analysed for the tissue effect of PJ and HTC. There was no
      significant difference in the mean +/- SD depth of tissue damage seen between PJ
      and HTC in the uterus (0.63 +/- 0.19 vs. 0.68 +/- 0.18; P = 0.481), ovary (0.61
      +/- 0.14 vs. 0.67 +/- 0.15; P = 0.420) and fallopian tube (0.63 +/- 0.18 vs. 0.60
      +/- 0.13; P = 0.688). A significantly lesser lateral spread of tissue damage
      (width) was seen with PJ than HTC in all three tissue types (uterus: 4.66 +/-
      0.91 vs. 7.67 +/- 1.21, P < 0.001; ovary: 4.05 +/- 0.61 vs. 5.90 +/- 0.95, P <
      0.001; fallopian tube: 4.50 +/- 0.77 vs. 6.00 +/- 1.28, P = 0.034). CONCLUSION:
      The depth of tissue damage caused by PJ at 20 % power is comparable to that with
      HTC on gynaecological tissues. The lateral spread (width of tissue damage) is
      however lesser with PJ than with HTC.

PMID- 22467150
TI  - Bacteremia and intrauterine infection with Shigella sonnei in a pregnant woman
      with AIDS.

PMID- 22467151
TI  - Multi-detector computed tomography venography in the assessment of dysfunction of
      tunneled hemodialysis central vein catheters.
AB  - PURPOSE: To assess the value of multi-detector computed tomography venography
      (MDCTV) in the assessment of tunneled hemodialysis central vein catheters (CVCs)
      dysfunction. METHODS: Twenty-five patients who had tunneled CVC dysfunction
      without abnormality found by x-ray and ultrasound were enrolled. Anti-platelet
      agents, anticoagulants, and thrombolytic therapy with urokinase failed to resume
      normal catheter function. MDCTV was performed to observe the position of
      catheters and to detect central venous stenosis, thrombosis, and fibrin sheath
      formation. Correct intervention was given according to MDCTV results. RESULTS:
      MDCTV revealed that the catheter was malpositioned in 10 cases; there were five
      cases of central venous stenosis, four cases of central venous thrombosis, one
      case of fibrin sheath formation, and the other five had no abnormalities found.
      Blood flow on hemodialysis had reached over 300 mL/min after correct
      intervention. CONCLUSIONS: MDCTV provided a new possible way to assess
      dysfunction of tunneled hemodialysis central venous catheters.

PMID- 22467152
TI  - Safety and efficacy of StarClose SE Vascular Closure System in high-risk liver
      interventional oncology patients.
AB  - PURPOSE: To assess the safety and efficacy of the StarClose SE Vascular Closure
      System (Abbott Vascular, Abbott Park IL, USA) in high-risk thrombocytopenic and
      coagulopathic interventional oncology (IO) patients. METHODS: In this single
      institution retrospective study, 63 high-risk thrombocytopenic or coagulopathic
      IO patients (M:F=51:12, mean age 58 years, range 31-88 years) who underwent 83
      common femoral arteriotomy closures using the StarClose device were identified
      among all IO patients (n=131) undergoing StarClose closure (n=177) between 2008
      2011. High-risk thrombocytopenia and coagulopathy were defined as platelet count
      <=100 10(3)/mL and international normalized ratio (INR) >=1.5. Procedures
      included chemoembolization (n=67), radioembolization (n=8), and hepatic arterial
      mapping with technetium-99m macroaggrated albumin administration (n=8) for
      treatment of hepatocellular carcinoma (n=79) or liver metastases (n=4). Measured
      outcomes included technical success of arterial closure and closure-related
      adverse events, graded according to the Society of Interventional Radiology
      classification. RESULTS: In all cases, 5 French common femoral arterial access
      was used. Platelet count was <=100 10(3)/mL in 80/83 (96.4%) cases and INR was
      >=1.5 in 35/83 (42.2%) cases. Mean pre-procedure platelet count was 71 (range 26
      347) 10(3)/mL and mean INR was 1.4 (range 1.0-2.1). The StarClose device
      effectively sealed the arteriotomy in 83/83 (100%) cases, 60/83 (72.3%) cases
      were first-time closures, and 20/83 (24.1%) cases were repeat closures. Small
      groin hematomas, graded as class A minor complications, developed in 3/83 (3.6%)
      cases. No other complications were encountered. CONCLUSIONS: The StarClose SE
      Vascular Closure System confers high technical success and safety in common
      femoral arteriotomy closure in high-risk IO patients.

PMID- 22467153
TI  - Video-assisted two-stage basilic vein transposition for creation of brachio
      basilic arteriovenous fistulae.

PMID- 22467154
TI  - Marivita geojedonensis sp. nov., isolated from seawater.
AB  - A Gram-negative-staining, non-motile, non-spore-forming, aerobic and rod-shaped
      bacterial strain, DPG-138(T), was isolated from seawater on the southern coast in
      Korea. Strain DPG-138(T) grew optimally at 30  degrees C and in the presence of 2
      3 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene
      sequences revealed that strain DPG-138(T) fell within the cluster comprising the
      type strains of four species of the genus Marivita (sequence similarity values of
      97.8-98.2 %). The DNA G+C content was 59.9 mol%. The predominant ubiquinone of
      strain DPG-138(T) was Q-10, typical for the genus Marivita. The cellular fatty
      acid profiles of strain DPG-138(T) and type strains of four species of the genus
      Marivita were similar with C(18 : 1)omega7c as the most common fatty acid. The
      major polar lipids in strain DPG-138(T) were phosphatidylcholine,
      phosphatidylglycerol, phosphatidylethanolamine and one unidentified aminolipid.
      Differential phenotypic properties and genetic distinctiveness of strain DPG
      138(T) demonstrated that this strain is distinguishable from all four recognized
      species of the genus Marivita. On the basis of the data presented, strain DPG
      138(T) is considered to represent a novel species of the genus Marivita, for
      which the name Marivita geojedonensis sp. nov. is proposed. The type strain is
      DPG-138(T) ( = KCTC 23882(T) = CCUG 62112(T)).

PMID- 22467155
TI  - Burkholderia diazotrophica sp. nov., isolated from root nodules of Mimosa spp.
AB  - Five strains, JPY461(T), JPY359, JPY389, DPU-3 and STM4206 were isolated from
      nitrogen-fixing nodules on the roots of Mimosa spp. and their taxonomic positions
      were investigated using a polyphasic approach. All five strains grew at 15-40 
      degrees C (optimum, 30-37  degrees C), at pH 4.0-8.0 (optimum, pH 6.0-7.0) and
      with 0-1 % (w/v) NaCl [optimum, 0 % (w/v)]. On the basis of 16S rRNA gene
      sequence analysis, a representative strain (JPY461(T)) showed 97.2 % sequence
      similarity to the closest related species Burkholderia acidipaludis SA33(T), a
      similarity of 97.2 % to Burkholderia terrae KMY02(T), 97.1 % to Burkholderia
      phymatum STM815(T) and 97.1 % to Burkholderia hospita LMG 20598(T). The
      predominant fatty acids of the five novel strains were summed feature 2
      (comprising C(16 : 1) iso I and/or C(14 : 0) 3-OH), summed feature 3 (comprising
      C(16 : 1)omega7c and/or C(16 : 1)omega6c), C(16 : 0) , C(16 : 0) 3-OH, C(17 : 0)
      cyclo, C(18 : 1)omega7c and C(19 : 0) cyclo omega8c. The major isoprenoid quinone
      was Q-8 and the DNA G+C content of the strains was 63.0-65.0 mol%. The polar
      lipid profile consisted of a mixture of phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, an unidentified aminophospholipid,
      an unidentified aminolipid and several unidentified phospholipids. The DNA-DNA
      relatedness of the novel strain with respect to recognized species of the genus
      Burkholderia was less than 54 %. On the basis of 16S rRNA and recA gene sequence
      similarities, chemotaxonomic and phenotypic data, the five strains represent a
      novel species in the genus Burkholderia, for which the name Burkholderia
      diazotrophica sp. nov. is proposed with the type strain, JPY461(T) ( = LMG
      26031(T) = BCRC 80259(T) = KCTC 23308(T)).

PMID- 22467156
TI  - Paenibacillus oceanisediminis sp. nov. isolated from marine sediment.
AB  - A Gram-stain-negative, non-motile, aerobic, endospore forming and rod-shaped
      bacterium, designated strain L10(T), was isolated from marine sediment collected
      from the South Korean coast. The organism grew optimally under conditions of 30 
      degrees C, 1 % (w/v) NaCl and pH 6.0. It was oxidase-negative and catalase
      positive. Phylogenetic analysis based on 16S rRNA gene sequences indicated that
      strain L10(T) was associated with the genus Paenibacillus and most closely
      related to Paenibacillus barcinonensis BP-23(T) (98.2 % similarity). The major
      fatty acids of strain L10(T) were iso-C(14 : 0), anteiso-C(15 : 0) and iso-C(16 :
      0). The cell-wall peptidoglycan was the A1gamma type, and the predominant
      isoprenoid quinone was menaquinone-7. Strain L10(T) contained two unidentified
      lipids, an unidentified amino-phospholipid, phosphatidylethanolamine,
      phosphatidylglycerol, and diphosphatidylglycerol. The G+C content of the genomic
      DNA was 44 mol% and the DNA-DNA hybridization values with closely related strains
      were below 14+/-2 %. Based on phenotypic, genotypic, and phylogenetic data,
      strain L10(T) should be classified as a novel species within the genus
      Paenibacillus. The name Paenibacillus oceanisediminis sp. nov. is proposed. The
      type strain is L10(T) ( = KACC 16203(T) = JCM 17814(T)).

PMID- 22467157
TI  - Porphyromonas crevioricanis is an earlier heterotypic synonym of Porphyromonas
      cansulci and has priority.
AB  - A DNA-DNA hybridization experiment was carried out to clarify the relationship
      between Porphyromonas crevioricanis and Porphyromonas cansulci. The taxonomic
      standing of these two species was unclear so far because of the high 16S rRNA
      gene sequence similarity value (99.9 %). The DNA-DNA relatedness values between
      P. crevioricanis JCM 15906(T) and P. cansulci JCM 13913(T) were above 91 % (91-99
      %). In addition, P. crevioricanis JCM 15906(T) exhibited high hsp60 gene sequence
      similarity with P. cansulci JCM 13913(T) (100 %). The hsp60 gene sequence
      analysis and the DNA-DNA relatedness values demonstrated that P. crevioricanis
      JCM 15906(T) and P. cansulci JCM 13913(T) are a single species. Based on these
      data, we propose Porphyromonas cansulci as a later heterotypic synonym of
      Porphyromonas crevioricanis.

PMID- 22467158
TI  - Streptococcus troglodytidis sp. nov., isolated from a foot abscess of a
      chimpanzee (Pan troglodytes).
AB  - A facultative anaerobic, non-motile, non-spore-forming, Gram-positive-staining,
      coccus-shaped bacterium was isolated from an abscess on the right foot of a
      chimpanzee (Pan troglodytes). The colonies were beta-haemolytic. Catalase and
      oxidase activities were negative. The Lancefield group B antigen was expressed.
      On the basis of morphological and biochemical characteristics, the bacterium was
      tentatively identified as a streptococcal species. 16S rRNA gene sequence
      analysis indicated that the bacterium shared 96.7 %, 96.4 %, 96.1 %, 95.8 % and
      95.7 % sequence similarities with Streptococcus gordonii, S. cristatus, S.
      intermedius, S. anginosus and S. constellatus, respectively. Phylogenetic
      analyses based on the sequences of the 16S rRNA gene and housekeeping genes
      encoding D-alanine : D-alanine ligase (ddl), the beta-subunit of RNA polymerase
      (rpoB) and manganese-dependent superoxide dismutase (sodA) revealed that the
      bacterium represented a novel species closely related to, albeit different from,
      S. gordonii, S. cristatus and the anginosus streptococci. The name Streptococcus
      troglodytidis sp. nov. is proposed. The type strain is M09-11185(T) ( = ATCC BAA
      2337(T) = KCTC 33006(T)).

PMID- 22467159
TI  - New technologies for the assessment of chromosomes in prenatal diagnosis.

PMID- 22467160
TI  - QF-PCR: application, overview and review of the literature.
AB  - Quantitative fluorescent polymerase chain reaction has been in diagnostic use in
      the UK for over 10 years and has proved to be a cost-effective, robust and
      accurate rapid prenatal test for common aneuploidies. Specific advantages include
      detection of triploidy, mosaicism and maternal cell contamination. Its
      application at our centre is described, with developments including stand-alone
      testing and improvements in strategies for the preparation and testing of
      chorionic villus biopsies.

PMID- 22467161
TI  - Multiplex ligation-dependent probe amplification (MLPA) and prenatal diagnosis.
AB  - Multiplex ligation-dependent probe amplification (MLPA) is a recent technique for
      the relative quantitation of up to 40 to 45 nucleic acid targets. Due to its
      relative simplicity, low cost, and availability of laboratory-developed and more
      than 300 commercially-developed assays, MLPA has become more widely used for both
      research and diagnostic applications. The MLPA platform is now extensively
      applied for postnatal diagnosis of genetic disorders and has recently been used
      for prenatal diagnosis. The published uses of MLPA for prenatal diagnosis include
      detection of aneuploidies, common microdeletion syndromes and subtelomeric copy
      number changes, identification of marker chromosomes, and detection of familial
      copy-number changes in single genes. This review describes the technique of MLPA
      in detail and offers considerations for the interpretation of results in the
      clinical diagnostic setting. (c) 2012 John Wiley & Sons, Ltd.

PMID- 22467162
TI  - Same-day prenatal diagnosis of common chromosomal aneuploidies using
      microfluidics-fluorescence in situ hybridization.
AB  - Rapid molecular prenatal diagnostic methods, such as fluorescence in situ
      hybridization (FISH), quantitative fluorescence-PCR, and multiplex ligation
      dependent probe amplification, can detect common fetal aneuploidies within 24 to
      48 h. However, specific diagnosis or aneuploidy exclusion should be ideally
      available within the same day as fetal sampling to alleviate parental anxiety.
      Microfluidic technologies integrate different steps into a microchip, saving time
      and costs. We have developed a cost-effective, same-day prenatal diagnostic FISH
      assay using microfluidics. Amniotic fluids (1-4 mL from 40 pregnant women at 15
      22 weeks of gestation) were fixed with Carnoy's before loading into the
      microchannels of a microfluidic FISH-integrated nanostructured device. The glass
      slides were coated with nanostructured titanium dioxide to facilitate cell
      adhesion. Pretreatment and hybridization were performed within the microchannels.
      Fifty nuclei were counted by two independent analysts, and all results were
      validated with their respective karyotypes. Of the 40 samples, we found three
      cases of fetal aneuploidies (trisomies 13, 18, and 21), whereas the remaining 37
      cases were normal. Results were concordant with their karyotypes and ready to be
      released within 3 h of sample receipt. Microfluidic FISH, using 20-fold less than
      the recommended amount of probe, is a cost-effective method to diagnose common
      fetal aneuploidies within the same day of fetal sampling.

PMID- 22467163
TI  - Prenatal BACs-on-BeadsTM: the prospective experience of five prenatal diagnosis
      laboratories.
AB  - OBJECTIVE: We previously reported on the validation of Prenatal BACs-on-BeadsTM
      on retrospectively selected and prospective prenatal samples. This bead-based
      multiplex assay detects chromosome 13, 18, 21 and X/Y aneuploidies and the nine
      most frequent microdeletion syndromes. We demonstrated that Prenatal BACs-on
      Beads(TM) is a new-generation, prenatal screening tool. Here, we describe the
      experience of five European prenatal diagnosis laboratories concerning the
      ongoing use of Prenatal BACs-on-BeadsTM . METHODS: Some 1653 samples were
      analyzed. All results were confirmed by conventional karyotyping or another
      appropriate technique. All indications for invasive prenatal diagnosis were
      included. Amniotic fluid and chorionic villus samples were analyzed in equivalent
      proportions. RESULTS: The failure rate was 3.3% and the overall abnormality
      detection rate was ~1/10. Eighty-five percent of the detected abnormalities were
      common aneuploidies. Eleven microdeletions and duplications were identified, thus
      giving an overall yield for microdeletion and microduplication detection of
      1/145. Compared with QF-PCR, Prenatal BACs-on-BeadsTM provides an additional
      detection rate of ~1/250 for low-risk pregnancies. The false positive and
      negative rates were both <1%. CONCLUSION: When associated with conventional
      karyotyping, the Prenatal BACs-on-BeadsTM assay combines a short turnaround time
      (typical of rapid aneuploidy detection tests) with valuable detection of the most
      frequent microdeletion syndromes that cannot be detected in cytogenetic analyses.

PMID- 22467164
TI  - Genomic microarrays: a technology overview.
AB  - Genomic microarrays are now widely used diagnostically for the molecular
      karyotyping of patients with intellectual disability, congenital anomalies and
      autistic spectrum disorder and have more recently been applied for the detection
      of genomic imbalances in prenatal genetic diagnosis. We present an overview of
      the different arrays, protocols used and discuss methods of genomic array data
      analysis.

PMID- 22467165
TI  - Referral patterns for microarray testing in prenatal diagnosis.
AB  - OBJECTIVE: To understand the prenatal referral patterns from the United States,
      Canada, and Israel for two whole-genome microarray platforms, each with a
      different resolution. METHOD: Physicians selected one of the two array designs to
      be performed on 1483 prenatal specimens for a 1-year period. We retrospectively
      examined detection rates, indications for study, and physician array selection.
      RESULTS: The lower resolution array (55 K) showed an ~32% decrease in the
      detection of results of unclear clinical significance while retaining the ability
      to detect all but one significant abnormality identified by the higher resolution
      array (135 K). A majority of samples were referred for abnormal ultrasound
      findings. Whereas the United States and Canada utilized the higher resolution
      array more often for this indication, Israel preferred the 55 K array. Referral
      patterns for parental anxiety were similar for the United States and Israel, with
      most cases being tested on the 55 K array. Few cases were referred for advanced
      maternal age or family history of a genetic condition from either Canada or
      Israel. CONCLUSION: Referral patterns varied between the countries and between
      indications for study. Understanding these differences will provide laboratories
      the critical information needed to develop array designs to meet the medical
      needs and patient desires for prenatal testing.

PMID- 22467166
TI  - Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience
      with >1000 cases and review of the literature.
AB  - OBJECTIVE: To evaluate the results of prenatal chromosomal microarray analysis
      (CMA) on >1000 fetal samples referred for testing at our institution and to
      compare these data to published reports. METHODS: High resolution CMA was offered
      to women undergoing amniocentesis or chorionic villus sampling. Parental samples
      were obtained concurrently to exclude maternal cell contamination and assist
      interpretation of copy number variations. RESULTS: Clinically significant copy
      number variations were observed in 85/1115 cases (7.6%) overall, and in 45/1075
      cases (4.2 %) if 40 abnormal cases with known chromosome abnormalities or
      familial genomic imbalances were excluded. Eighteen of the 1115 cases had
      variants of unclear clinical significance (1.6%). Indications yielding the most
      clinically significant findings were abnormal karyotype/fluorescence in situ
      hybridization (26/61, 42.6%), family history of chromosomal abnormality (13/137,
      9.5%), abnormal ultrasound (38/410, 9.3%), abnormal serum screening (2/37, 5.4%)
      and advanced maternal age (5/394, 1.3%). Of 1075 cases having no previously known
      cytogenetic abnormality or family history, 18 (1.7%) had clinically significant
      genomic changes undetectable by conventional prenatal chromosome analysis.
      CONCLUSION: Current experience confirms that the detection rate of CMA for
      prenatal chromosomal abnormalities surpasses that of conventional karyotype
      analysis and continues to improve with higher resolution arrays, while
      maintaining a low frequency of results of unclear clinical significance.

PMID- 22467167
TI  - Non-targeted whole genome 250K SNP array analysis as replacement for karyotyping
      in fetuses with structural ultrasound anomalies: evaluation of a one-year
      experience.
AB  - OBJECTIVE: We evaluated both clinical and laboratory aspects of our new strategy
      offering quantitative fluorescence (QF)-PCR followed by non-targeted whole genome
      250K single-nucleotide polymorphism array analysis instead of routine karyotyping
      for prenatal diagnosis of fetuses with structural anomalies. METHODS: Upon the
      detection of structural fetal anomalies, parents were offered a choice between QF
      PCR and 250K single-nucleotide polymorphism array analysis (QF/array) or QF-PCR
      and routine karyotyping (QF/karyo). RESULTS: Two hundred twenty fetal samples
      were included. In 153/220 cases (70%), QF/array analysis was requested. In 35/153
      (23%), an abnormal QF-PCR result was found. The remaining samples were analyzed
      by array, which revealed clinically relevant aberrations, including two known
      microdeletions, in 5/118 cases. Inherited copy number variants were detected in
      11/118 fetuses, copy number variants with uncertain clinical relevance in 3/118
      and homozygous stretches in 2/118. In 67/220 (30%) fetuses, QF/karyo was
      requested: 23/67 (34%) were abnormal with QF-PCR, and in 3/67, an abnormal
      karyotype was found. CONCLUSION: Even though QF/array does not reveal a high
      percentage of submicroscopic aberrations in fetuses with unselected structural
      anomalies, it is preferred over QF/karyo, as it provides a whole genome scan at
      high resolution, without additional tests needed and with a low chance on
      findings not related to the ultrasound anomalies.

PMID- 22467168
TI  - The role of DNA microarrays in the evaluation of fetal death.
AB  - Fetal death occurs in 15% of clinically recognized pregnancies. Cytogenetic
      abnormalities are present in 50% of spontaneous abortions (fetal deaths < 20
      weeks) whereas the rate is 6% to 13% for stillbirths (fetal deaths >= 20 weeks).
      Microarray has been demonstrated to increase the diagnosis of genetic
      abnormalities by providing coverage of the entire genome at a higher density,
      detecting as small as 50 to 100 kb deletions or duplications, known as copy
      number changes. Microarray is particularly suited for evaluation of fetal death
      because DNA can still be analyzed in macerated fetuses and nonviable tissue, two
      situations where culturing and karyotyping is known to have low yield. Microarray
      has already proven successful in providing additional genetic information beyond
      karyotype in spontaneous abortion. The few studies on the use of microarray in
      stillbirth evaluation have been promising, demonstrating an increase in the
      diagnosis of clinically relevant genetic abnormalities when compared with
      karyotype. As the cost and technology improve, microarray may ultimately become
      the first line screen for genetic abnormalities in stillbirth. The accurate
      diagnosis of a genetic abnormality as the cause for fetal death may provide
      closure for families, prevent unnecessary treatments, and enable clinicians to
      more accurately counsel and manage subsequent pregnancies.

PMID- 22467169
TI  - Genetic counselling and ethical issues with chromosome microarray analysis in
      prenatal testing.
AB  - Molecular karyotyping using chromosome microarray analysis (CMA) detects more
      pathogenic chromosomal anomalies than classical karyotyping, making CMA likely to
      become a first tier test for prenatal diagnosis. Detecting copy number variants
      of uncertain clinical significance raises ethical considerations. We consider the
      risk of harm to a woman or her fetus following the detection of a copy number
      variant of uncertain significance, whether it is ethically justifiable to
      withhold any test result information from a woman, what constitutes an 'informed
      choice' when women are offered CMA in pregnancy and whether clinicians are
      morally responsible for 'unnecessary' termination of pregnancy. Although we are
      cognisant of the distress associated with uncertain prenatal results, we argue in
      favour of the autonomy of women and their right to information from genome-wide
      CMA in order to make informed choices about their pregnancies. We propose that
      information material to a woman's decision-making process, including uncertain
      information, should not be withheld, and that it would be paternalistic for
      clinicians to try to take responsibility for women's decisions to terminate
      pregnancies. Non-directive pre-test and post-test genetic counselling is central
      to the delivery of these ethical objectives.

PMID- 22467170
TI  - Integration of microarray technology into prenatal diagnosis: counselling issues
      generated during the NICHD clinical trial.
AB  - Cytogenetic microarray analysis (CMA) in prenatal testing detects chromosome
      abnormalities and new genetic syndromes that would be missed by conventional
      cytogenetics and has the potential to significantly enhance prenatal genetic
      evaluation. A large Eunice Kennedy Shriver National Institute Of Child Health and
      Human Development (NICHD)-sponsored multicentered trial to assess the role of CMA
      as a primary prenatal diagnostic tool has been completed, and results will soon
      be available. Integration of this technology into clinical care will require
      thoughtful changes in patient counseling. Here, we examine four cases, all
      ascertained in the NICHD prenatal microarray study, to illustrate the challenges
      and subtleties of genetic counseling required with prenatal CMA testing. Although
      the specifics of each case are distinct, the underlying genetic principles of
      uncertainty, variable expressivity, and lack of precise genotype-phenotype
      correlation are well known and already part of prenatal counseling. Counselor and
      practitioner education will need to include both the science of interpreting
      array findings as well as development of improved approaches to uncertainty. A
      team approach to interpretation will need to be developed, as will standardized
      guidelines by professional organizations and laboratories. Of equal import is
      additional research into patient attitudes and desires, and a better
      understanding of the full phenotypic spectrum of copy number variants discovered
      in utero.

PMID- 22467171
TI  - Noninvasive prenatal diagnosis empowered by high-throughput sequencing.
AB  - BACKGROUND: Noninvasive prenatal diagnosis of fetal Down syndrome using direct
      nucleic acid analysis was once an elusive goal. The presence of cell-free fetal
      DNA in maternal plasma was discovered in 1997 and offered a new noninvasive
      source of fetal genetic material. METHOD: A number of approaches have since been
      developed for the assessment of fetal chromosome dosage based on cellfree fetal
      DNA analysis. The most effective approach developed to date is based on massively
      parallel sequencing of maternal plasma DNA molecules for the detection of an
      increased representation of chromosome 21 DNA molecules in the plasma of women
      pregnant with trisomy 21 fetuses when compared with euploid pregnancies. RESULT
      AND CONCLUSION: A number of multicenter studies have since been conducted to
      evaluate the diagnostic efficacy of the sequencing-based method. To date, the
      literature contains results for the analysis of a total of 305 trisomy 21
      pregnancies and 2061 euploid pregnancies. The overall diagnostic sensitivity and
      specificity were both 99%. Besides trisomy 21, massively parallel maternal plasma
      DNA sequencing has also been applied to the noninvasive detection of trisomy 18,
      trisomy 13 and fetal genetic sequences across the genome.

PMID- 22467172
TI  - Suppression of Tak1 promotes prostate tumorigenesis.
AB  - More than 30% of primary prostate cancers contain a consensus deletion of an
      approximately 800 kb locus on chromosome 6q15.1. The MAP3K7 gene, which encodes
      TGF-beta activated kinase-1 (Tak1), is a putative prostate tumor suppressor gene
      within this region whose precise function remains obscure. In this study, we
      investigated the role of Tak1 in human and murine prostate cancers. In 50 well
      characterized human cancer specimens, we found that Tak1 expression was
      progressively lost with increasing Gleason grade, both within each cancer and
      across all cancers. In murine prostate stem cells and Tak1-deficient prostatic
      epithelial cells, Tak1 loss increased proliferation, migration, and invasion.
      When prostate stem cells attenuated for Tak1 were engrafted with fetal urogenital
      mesenchyme, the histopathology of the grafts reflected the natural history of
      prostate cancer leading from prostatic intraepithelial neoplasia to invasive
      carcinoma. In the grafts containing Tak1-suppressed prostate stem cells, p38 and
      c-jun-NH(2)-kinase activity was attenuated and proliferation was increased.
      Together, our findings functionally validate the proposed tumor suppressor role
      of Tak1 in prostate cancer.

PMID- 22467173
TI  - Estrogen promotes ER-negative tumor growth and angiogenesis through mobilization
      of bone marrow-derived monocytes.
AB  - Estrogen has a central role in the genesis and progression of breast cancers
      whether they are positive or negative for the estrogen receptor (ER). While
      therapies that disrupt estrogen biosynthesis or ER activity can treat these
      diseases in postmenopausal women, in younger women where ovarian function remains
      intact, these anti-estrogen therapies are not as effective. Moreover, emerging
      clinical evidence suggests that estrogen may promote other cancers. Thus,
      circulating estrogens may participate in cancer pathogenesis in ways that are not
      yet understood. In this study, we show that estrogen can promote the outgrowth of
      murine xenograft tumors established from patient-derived ER-negative breast
      cancer cells by influencing the mobilization and recruitment of a proangiogenic
      population of bone marrow-derived myeloid cells. ERalpha expression was necessary
      and sufficient in the bone marrow-derived cells themselves to promote tumor
      formation in response to estrogen. Our findings reveal a novel way in which
      estrogen promotes tumor formation, with implications for the development and
      application of anti-estrogen therapies to treat cancer in premenopausal women.

PMID- 22467174
TI  - Compaction through buckling in 2D periodic, soft and porous structures: effect of
      pore shape.
AB  - Soft cellular structures that comprise a solid matrix with a square array of
      holes open avenues for the design of novel soft and foldable structures. Our
      results demonstrate that by simply changing the shape of the holes the response
      of porous structure can be easily tuned and soft structures with optimal
      compaction can be designed.

PMID- 22467175
TI  - Developing mutually encapsulating materials for versatile syntheses of multilayer
      metal-silica-polymer hybrid nanostructures.
AB  - New methods to self-assemble polystyrene-block-poly(acrylic acid) (PSPAA) on
      silica via electrostatic interaction and to deposit silica on PSPAA shells are
      developed. The mutual encapsulation of silica and PSPAA allows versatile
      syntheses of well-controlled nanohybrids.

PMID- 22467176
TI  - Abnormal development at early postimplantation stage in mouse embryos after
      preimplantation genetic diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) is an established procedure for the
      genetic analysis of embryos. To assess the effect of the procedure on early
      embryonic development, we generated a murine experimental system, including mice
      implanted with biopsied in vitro cultured embryos, control mice implanted with in
      vitro cultured embryos without biopsy, and mice with naturally conceived embryos.
      Embryos at the 7.5-dpc stage were isolated from all three groups and the embryo
      implantation rate, the survival rate of implanted embryos, and the developmental
      stage of surviving embryos were carefully assessed and compared among all three
      groups. We found the implantation rate was similar between biopsied and control
      group embryos (67.92% vs. 66.67%). However, the survival rate of implanted
      embryos in the biopsied group (49.31%) was significantly lower than that of the
      control (60.91%) and normal groups (96.24%) at 7.5 dpc. In addition, the survival
      rate of control group embryos was significant lower than that of normal group
      embryos. Classification of the precise developmental stages of randomly selected
      live implanted embryos at 7.5 dpc revealed no differences among the three groups.
      Our results indicate that blastomere biopsy does not adversely affect embryo
      implantation. The PGD procedure, in particular blastomere biopsy, increases the
      rate of embryo death at 4.5-7.5 dpc, but does not affect the development of
      surviving 7.5 dpc embryos.

PMID- 22467177
TI  - Theoretical investigation of biomass productivities achievable in solar
      rectangular photobioreactors for the cyanobacterium Arthrospira platensis.
AB  - Modeling was done to simulate whole-year running of solar rectangular
      photobioreactors (PBRs). Introducing the concept of ideal reactor, the maximal
      biomass productivity that could be achieved on Earth on nitrate as N-source was
      calculated. Two additional factors were also analyzed with respect to dynamic
      calculations over the whole year: the effect of PBR location and the effects of
      given operating conditions on the resulting decrease in productivity compared
      with the ideal one. Simulations were conducted for the cyanobacterium Arthospira
      platensis, giving an ideal productivity (upper limit) in the range 55-60 tX ha(
      1) year(-1) for a sun tracking system (and around 35-40 tX ha(-1) year(-1) for a
      fixed horizontal PBR). For an implantation in France (Nantes, west coast), the
      modification in irradiation conditions resulted in a decrease in biomass
      productivity of 40%. Various parameters were investigated, with special emphasis
      on the influence of the incident angle of solar illumination on resulting
      productivities, affecting both light capture and light transfer inside the bulk
      culture. It was also found that with appropriate optimization of the residence
      time as permitted by the model, productivities close to maximal could be achieved
      for a given location.

PMID- 22467180
TI  - Nucleotide sequencing and serologic analysis of Cache Valley virus isolates from
      the Yucatan Peninsula of Mexico.
AB  - Nucleotide sequencing was performed on part of the medium and large genome
      segments of 17 Cache Valley virus (CVV) isolates from the Yucatan Peninsula of
      Mexico. Alignment of these sequences to all other sequences in the Genbank
      database revealed that they have greatest nucleotide identity (97-98 %) with the
      equivalent regions of Tlacotalpan virus (TLAV), which is considered to be a
      variety of CVV. Next, cross-plaque reduction neutralization tests (PRNTs) were
      performed using sera from mice that had been inoculated with a representative
      isolate from the Yucatan Peninsula (CVV-478) or the prototype TLAV isolate (61-D
      240). The PRNT titers exhibited a twofold difference in one direction and no
      difference in the other direction suggesting that CVV-478 and 61-D-240 belong to
      the same CVV subtype. In conclusion, we demonstrate that the CVV isolates from
      the Yucatan Peninsula of Mexico are genetically and antigenically similar to the
      prototype TLAV isolate.

PMID- 22467179
TI  - Broad geographical distribution and high genetic diversity of shrew-borne Seewis
      hantavirus in Central Europe.
AB  - For a long time hantaviruses were believed to be exclusively rodent-borne
      pathogens. Recent findings of numerous shrew- and mole-borne hantaviruses raise
      important questions on their phylogenetic origin. The objective of our study was
      to prove the presence and distribution of shrew-associated Seewis virus (SWSV) in
      different Sorex species in Central Europe. Therefore, a total of 353 Sorex
      araneus, 59 S. minutus, 27 S. coronatus, and one S. alpinus were collected in
      Germany, the Czech Republic, and Slovakia. Screening by hantavirus-specific L
      segment RT-PCR revealed specific amplification products in tissues of 49 out of
      353 S. araneus and four out of 59 S. minutus. S-segment sequences were obtained
      for 45 of the L-segment positive S. araneus and all four L-segment positive S.
      minutus. Phylogenetic investigation of these sequences from Germany, the Czech
      Republic, and Slovakia demonstrated their similarity to SWSV sequences from
      Hungary, Finland, Austria, and other sites in Germany. The low intra-cluster
      sequence variability and the high inter-cluster divergence suggest a long-term
      SWSV evolution in isolated Sorex populations. In 28 of the 49 SWSV S-segment
      sequences, an additional putative open reading frame (ORF) on the opposite strand
      to the nucleocapsid protein-encoding ORF was identified. This is the first
      comprehensive sequence analysis of SWSV strains from Germany, the Czech Republic,
      and Slovakia, indicating its broad geographical distribution and high genetic
      divergence. Future studies have to prove whether both S. araneus and S. minutus
      represent SWSV reservoir hosts or spillover infections are responsible for the
      parallel molecular detection of SWSV in both species.

PMID- 22467181
TI  - On the future of genetic risk assessment.
AB  - Next-generation sequencing (NGS) techniques have greatly accelerated the
      molecular elucidation of Mendelian disorders, and affordable NGS-based diagnostic
      tests are around the corner that promise to detect or rule out mutations in
      specific subsets of the known disease genes. Whole exome sequencing and shortly
      afterwards whole genome sequencing (WGS) will become an even more comprehensive
      alternative to such targeted tests. In view of the current enthusiasm to
      implement these methods, but also given their rapidly dropping costs, it is quite
      possible that WGS will soon be adopted as universal intake test in Clinical
      Genetics. Central databases and large-scale genotype-phenotype comparisons will
      be required to progressively identify the clinically relevant sequence variants
      and to distinguish them from neutral polymorphisms in the human genome, and these
      databases will become indispensable for the interpretation of individual genome
      sequences. In this scenario, there will be massively growing demand for genetic
      counselling, but the need for experienced syndromologists will not increase
      proportionally, as the success of the diagnostic process will become far less
      dependent on the ability of clinical geneticists to reliably recognize genetic
      syndromes.

PMID- 22467182
TI  - Acetylcholinesterase inhibitors and the risk of hip fracture in Alzheimer's
      disease patients: a case-control study.
AB  - Recent studies have reported the presence of acetylcholine (ACh) receptor
      subtypes in bone tissue, and have demonstrated that inhibition of the ACh
      receptors has negative effects on bone mass and fracture healing capacity.
      However, little is known about the potential clinical effects that increased ACh
      signaling might have on bone. Accordingly, this study was designed to determine
      whether the use of acetylcholinesterase inhibitors (AChEIs), a group of drugs
      that stimulate ACh receptors and are used to treat Alzheimer's disease (AD), is
      associated with a decreased risk of hip fracture in AD patients. To accomplish
      this objective, a case-control analysis was performed using the AD population,
      aged above 75 years, based in the local health area of the Carlos Haya Hospital,
      in Malaga, Spain. The cases were 80 AD patients that suffered a hip fracture
      between January 2004 and December 2008. The controls were 2178 AD patients
      without hip fracture followed at our health care area during the same period of
      time. Compared with patients who did not use AChEIs, the hip fracture adjusted
      odds ratio (OR) for users of AChEIs was 0.42 (95% confidence interval [CI], 0.24
      0.72), for users of rivastigmine was 0.22 (95% CI, 0.10-0.45), and for users of
      donepezil was 0.39 (95% CI, 0.19-0.76). Data were adjusted for the following
      parameters: body mass index, fall risk, smoking habits, cognition, dependence,
      degree of AD, comorbidity score, treatment with selective serotonin reuptake
      inhibitors, age, and gender. Our data suggests that use of AChEIs donepezil and
      rivastigmine is associated with a reduced risk of fractures in AD patients. Many
      elderly patients with AD disease who are at risk of developing osteoporosis may
      potentially benefit from therapy with the AChEIs donepezil and rivastigmine.

PMID- 22467178
TI  - P2 receptors for extracellular nucleotides in the central nervous system: role of
      P2X7 and P2Y2 receptor interactions in neuroinflammation.
AB  - Extracellular nucleotides induce cellular responses in the central nervous system
      (CNS) through the activation of ionotropic P2X and metabotropic P2Y nucleotide
      receptors. Activation of these receptors regulates a wide range of physiological
      and pathological processes. In this review, we present an overview of the current
      literature regarding P2X and P2Y receptors in the CNS with a focus on the
      contribution of P2X7 and P2Y(2) receptor-mediated responses to neuroinflammatory
      and neuroprotective mechanisms.

PMID- 22467183
TI  - Rapid biliary stent clogging: two case reports in a 12 year ERCP series.
AB  - Rapid biliary stent clogging is poorly documented in the literature. We present
      two case reports in a 12-year ERCP series and highlight the challenges involved.

PMID- 22467184
TI  - Complications and characteristics of patients referred to a joint diabetes renal
      clinic in Ireland.
AB  - BACKGROUND AND METHODS: Joint diabetes renal (JDR) clinics are recommended as the
      appropriate model of care to manage advanced diabetic-associated renal failure.
      We performed a retrospective review of clinical data and records of the first 60
      patients who attended our service and their follow-up at 12 months. RESULTS: Of
      the patients, 88 % had type 2 diabetes. At the first visit, 43 % had retinopathy,
      56 % had neuropathy, 48 % had overt cardiovascular disease, 13 % had a previous
      history of stroke and 36 % peripheral arterial disease. Ten percent had lower
      limb amputation and 33 % had never previously seen a diabetologist. Fifteen
      percent were still on metformin despite significant renal impairment, while 43 %
      were on three or more different antihypertensives. Sixty-eight percent were
      either on an ACE inhibitor or angiotensin receptor blocker. At 12 months, a trend
      towards a reduction in HbA1c (7.6 +/- 2.0 vs. 7.0 +/- 1.6 %, p = 0.14) and
      systolic (159.4 +/- 30.8 vs. 141.8 +/- 35.5 mmHg, p = 0.13) and diastolic blood
      pressure (73.2 +/- 9.3 vs. 69.2 +/- 9.4 mmHg, p = 0.075) was observed. No
      significant differences were found in the lipid profile or creatinine clearance
      within the group. CONCLUSION: Thirty-three percent of patients with advanced
      diabetic nephropathy had never previously seen a diabetes consultant and a
      significant proportion had other diabetes-related complications. Patients with
      diabetic nephropathy may therefore benefit from having a multidisciplinary input
      at a joint diabetes renal clinic.

PMID- 22467185
TI  - Does smoking influence Crohn's disease in the biologic era? The TABACROHN study.
AB  - BACKGROUND: While most studies have found a negative effect of smoking on Crohn's
      disease (CD) phenotype, more recent data have failed to reproduce this
      association, which might be due to a current wider use of thiopurines and
      biologic therapy. The TABACROHN study aimed at defining the impact of smoking on
      CD in the largest published series. METHODS: This multicenter cross-sectional
      study included 1170 CD patients. Patients were classified as nonsmokers, current
      smokers, or former smokers according to their present smoking status. Clinical
      data regarding disease characteristics, treatment, and complications were
      collected. RESULTS: Smokers were more frequently under maintenance treatment when
      compared to nonsmokers. In addition, current smokers presented higher use of
      biologic drugs compared to nonsmokers. Tobacco exposure and a higher tobacco load
      were independent predictors of need for maintenance treatment and stenosing
      phenotype, respectively. CONCLUSIONS: In the era of early and widespread use of
      immunosuppressants and biologics, tobacco exposure is an independent predictor of
      need for maintenance treatment, specifically biologic therapy. The wider use of
      biologics and immunosuppressants could account for the existence of no major
      differences in disease behavior and complications between nonsmokers and current
      smokers.

PMID- 22467186
TI  - Strain dependence of polarization and piezoelectric response in epitaxial BiFeO3
      thin films.
AB  - Epitaxial strain has recently emerged as a powerful means to engineer the
      properties of ferroelectric thin films, for instance to enhance the ferroelectric
      Curie temperature (T(C)) in BaTiO(3). However, in multiferroic BiFeO(3) thin
      films an unanticipated strain-driven decrease of T(C) was reported and ascribed
      to the peculiar competition between polar and antiferrodistortive instabilities.
      Here, we report a systematic characterization of the room-temperature
      ferroelectric and piezoelectric properties for strain levels ranging between 
      2.5% and +1%. We find that polarization and the piezoelectric coefficient
      increase by about 20% and 250%, respectively, in this strain range. These trends
      are well reproduced by first-principles-based techniques.

PMID- 22467187
TI  - Synthesis of large-area MoS2 atomic layers with chemical vapor deposition.
AB  - Large-area MoS(2)  atomic layers are synthesized on SiO(2)  substrates by
      chemical vapor deposition using MoO(3)  and S powders as the reactants. Optical,
      microscopic and electrical measurements suggest that the synthetic process leads
      to the growth of MoS(2)  monolayer. The TEM images verify that the synthesized
      MoS(2)  sheets are highly crystalline.

PMID- 22467188
TI  - An oocyte-preferential histone mRNA stem-loop-binding protein like is expressed
      in several mammalian species.
AB  - During early embryo development, chromatin packaging is sustained by histones of
      maternal origin. Most histone messenger RNAs are not polyadenylated, but rather
      end in an evolutionarily conserved stem-loop that controls RNA processing,
      nucleocytoplasmic transport, stability, and translation via interactions with a
      specific protein named stem-loop-binding protein (SLBP). In mouse oocytes, mSLBP
      is synthesized abundantly during maturation and activates histone translation. In
      Xenopus, xSLBP is present in stage-VI oocytes, but histone mRNA is protected from
      premature translation by the oocyte-specific Xenopus SLBP2 (xSLBP2) protein;
      during maturation xSLBP2 replacement by xSLBP results in histone synthesis. Here,
      we report the first experimental evidence and characterization of a mammalian
      SLBP2 ortholog. Bovine bSLBP and bSLBP2 display distinct expression patterns
      throughout oocyte maturation and pre-implantation embryo development. From the
      immature oocyte to the morula, bSLBP2 is concentrated in the nucleus, while it is
      homogeneously distributed throughout the cytoplasm in mature oocytes. A putative
      SLBP2 gene is conserved in the genome of several mammalian species, and the
      corresponding transcripts were detected in rat, dog, horse, and pig oocytes. By
      contrast, a pseudogene is found in mouse, human, and rabbit. Altogether, our data
      suggest that the availability of histones in oocytes is regulated by an
      alternative mechanism in bovine and other species as compared to mouse and frog.

PMID- 22467189
TI  - Drug formulations should be rational and uniform.

PMID- 22467190
TI  - Chronic epididymitis with scrotal vasocutaneous urinary fistula.
AB  - Chronic Epididymitis is a relatively rare problem in boys and is often enigmatic
      in its etiology. It is often associated with urinary tract abnormalities in
      infants and prepubertal children. This report describes a rare and unusual case
      of a chronic epididymitis with acquired scrotal vasocutaneous urinary fistula in
      an 8-mo-old boy who was found to have a large prostatic utricular cyst and
      ectopic vas insertion. The authors discuss embryology, pathophysiology,
      diagnostic dilemma and different treatment options.

PMID- 22467191
TI  - Results of phase I study of a multi-modality treatment for newly diagnosed
      glioblastoma multiforme using local implantation of concurrent BCNU wafers and
      permanent I-125 seeds followed by fractionated radiation and temozolomide
      chemotherapy.
AB  - Previously we demonstrated median survival of 69 weeks after combination therapy
      of permanent, low-activity I-125 seeds and BCNU wafers for recurrent glioblastoma
      multiforme (GBM). We designed this prospective phase I trial to assess efficacy
      of this combination treatment for newly diagnosed GBM. Patients with newly
      diagnosed GBMs deemed amenable to gross total resection were included. This dose
      escalation study of I-125 seeds included three 6-patient cohorts, receiving
      increasing doses of 3000, 6000, and 9000 cGy, and a maximal number of BCNU wafers
      placed surgically. Postoperatively patients underwent standard fractionated
      radiation to 5,940 cGy followed by temozolomide chemotherapy. During enrollment
      of the first 6-patient cohort, the trial was stopped when 3 of 5 patients
      developed radiation toxicity. Five patients (median age 55 years, range 46-64
      years) completed postoperative radiation; Karnofsky Performance Status ranged
      from 70 to 90. This lowest-dose cohort received I-125 seeds at 3,000 cGy and
      maximal BCNU wafer placement, and reached endpoint (median 26 weeks follow-up).
      Two patients developed local disease progression (median 34.4 weeks). The 3
      patients who developed radiation toxicity, which was documented on follow-up MRI
      and confirmed by MRI spectroscopy (median 20 weeks), underwent treatment with
      steroids and bevacizumab. Our phase I study was closed during enrollment of the
      first 6-patient cohort because of the high incidence (60 %) of early radiation
      toxicity. We do not recommend the seed-wafer therapy for newly diagnosed GBM
      patients but rather reserve this as salvage therapy for select patients with
      recurrent GBM.

PMID- 22467192
TI  - Prevalence of sleep breathing complaints reported by treatment-seeking chronic
      insomnia disorder patients on presentation to a sleep medical center: a
      preliminary report.
AB  - PURPOSE: Few studies have examined the co-morbidity between insomnia and sleep
      disordered breathing in the clinical setting. This study evaluated treatment
      seeking insomnia patients and their self-report of sleep breathing complaints.
      METHODS: A retrospective chart review was conducted on 1,035 consecutive
      treatment-seeking, chronic insomnia patients who reported insomnia as their
      primary problem upon seeking care at a private, community-based sleep medical
      center. Measurements included the insomnia severity index, standard subjective
      sleep measures as well as rankings, attributions, and self-reports about sleep
      breathing disorders, problems, and symptoms. RESULTS: A total of 1,035 adult,
      treatment-seeking insomnia patients indicated insomnia interfered with daytime
      functioning, and their average insomnia severity was in the range of a clinically
      relevant problem: total sleep time (5.50 h, SD = 1.60), sleep efficiency (71.05
      %, SD = 18.26), wake time after sleep onset (120.70 min, SD = 92.56), and an
      insomnia severity index (18.81, SD = 5.09). Of these 1,035 insomnia patients, 42
      % also ranked a sleep breathing disorder among their list of reasons for seeking
      treatment, another 13 % revealed a concern about a sleep breathing problem, and
      another 26 % reported awareness of sleep breathing symptoms. Only 19 % of this
      clinical insomnia sample reported no awareness or concerns about sleep breathing
      disorders, problems, or symptoms. A greater proportion of men than women reported
      significantly more sleep breathing disorders, problems, or symptoms. CONCLUSIONS:
      Sleep breathing complaints were extremely common among a large sample of
      treatment-seeking, self-identified, adult chronic insomnia patients. Prospective
      prevalence research is needed to corroborate or revise these findings, and
      polysomnography should be considered in appropriate cohorts to determine the
      clinical relevance of treatment-seeking chronic insomnia patients' sleep
      breathing complaints.

PMID- 22467194
TI  - Limits of the Epworth Sleepiness Scale in older adults.
AB  - PURPOSE: Excessive daytime sleepiness (EDS) in older adults is associated with
      obstructive sleep apnea, falls, reduced quality of life, and mortality. The
      Epworth Sleepiness Scale (ESS) is widely used to assess sleepiness. However, EDS
      assessment with the ESS may not be accurate in older adults. We aimed to (1)
      describe the responsiveness of nondemented older subjects to the ESS and (2)
      compare the self-report ESS scores to those of close relatives (CR) proxy and
      identify factors influencing any discrepancies between them. METHODS: This is a
      cross-sectional observational study including 104 independently living
      nondemented older subjects with daytime sleepiness complaints and 104 nondemented
      CRs. Cognitive tests (Mini-Mental State Examination) and the ESS were completed
      separately by subjects and CRs to assess the subject's daytime sleepiness.
      RESULTS: Almost 60 % of subjects and CRs were not able to answer at least one
      question on the ESS. Despite the fact that all subjects complained of EDS, only
      24 % of them had an abnormal ESS score (>10). Subjects rated their sleepiness
      lower (7.10 +/- 4.31) than their CR proxy did (9.70 +/- 5.14) (p < 0.0001). In
      multivariate analysis, an increase in age and a decrease in cognitive status of
      the subjects appeared related to the difference in ESS between subject and CR.
      CONCLUSIONS: The majority of older adults were not able to answer all of the ESS
      items. The ESS may underestimate sleepiness severity in older subjects. Despite
      EDS complaints in all subjects, only one quarter of them had a pathological ESS
      score.

PMID- 22467193
TI  - Bone mineral density in patients with obstructive sleep apnea syndrome.
AB  - PURPOSE: Obstructive sleep apnea syndrome (OSAS) is a disorder that is
      characterized by repetitive pauses in breathing during sleep. Airway obstruction
      episodes can lead to ischemia or hypoxia in tissues. Hypoxia may also have an
      effect on bone metabolism. In this study, we aim to investigate both the bone
      metabolic abnormalities and bone mineral density (BMD) in OSAS patients compared
      to individuals without OSAS. METHODS: Twenty-one male patients with OSAS and 26
      control subjects, also male, enrolled in this study. Serum calcium, phosphorus,
      alkaline phosphatase, and urinary desoxypiridinoline levels were measured in all
      participants, and BMD was evaluated using DEXA (Hologic QDR 2000). The BMD was
      measured in the lumbar spine (L1-L4), the femoral neck, and total femur region.
      RESULTS: No statistically significant difference was noted between the two groups
      with respect to demographic data, except for body mass index (BMI). We adjusted
      the statistical analyses in line with the BMI and noted significant differences
      between OSAS patients and control subjects with regard to lumbar L1-L4 t score,
      lumbar L1-L4 BMD, and femoral neck BMD values (p <= 0.001). We find significant
      correlations with lumbar L1-L4 BMD (r = -0.4; p = 0.023) and lumbar L1-L4 t score
      values (r = -0.5; p = 0.012). CONCLUSION: Our study indicates that there is a
      relationship between OSAS and osteoporosis. However, further controlled studies
      comprising a greater number of patients are needed to investigate the
      relationship between osteoporosis and OSAS.

PMID- 22467195
TI  - Positron emission tomography molecular imaging of dopaminergic system in drug
      addiction.
AB  - Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction
      remains unclear. Positron emission tomography (PET) is the first technology used
      for the direct measurement of components of the dopaminergic system in the living
      human brain. In this article, we reviewed the major findings of PET imaging
      studies on the involvement of DA in drug addiction, especially in heroin
      addiction. Furthermore, we summarized PET radiotracers that have been used to
      study the role of DA in drug addiction. To investigate presynaptic function in
      drug addiction, PET tracers have been developed to measure DA synthesis and
      transport. For the investigation of postsynaptic function, several radioligands
      targeting dopamine one (D1) receptor and dopamine two (D2) receptor are
      extensively used in PET imaging studies. Moreover, we also summarized the PET
      imaging findings of heroin addiction studies, including heroin-induced DA
      increases and the reinforcement, role of DA in the long-term effects of heroin
      abuse, DA and vulnerability to heroin abuse and the treatment implications. PET
      imaging studies have corroborated the role of DA in drug addiction and increase
      our understanding the mechanism of drug addiction.

PMID- 22467196
TI  - A strategy for simultaneously realizing the cubic-to-hexagonal phase transition
      and controlling the small size of NaYF4:Yb3+,Er3+ nanocrystals for in vitro cell
      imaging.
AB  - Hexagonal-phase NaYF(4):Yb(3+),Er(3+) up-conversion nanocrystals (UCNCs) are
      synthesized by a combination of refluxing and hydrothermal treatment. This
      strategy leads to only a slight increase in particle size, from 4.5 to ca. 10 nm,
      during the cubic-to-hexagonal phase transition. The hexagonal UCNCs can be
      internalized by HeLa cells and exhibit visible emission in the cells under near
      infrared excitation.

PMID- 22467197
TI  - Characterization of chromosomal mediated cadmium resistance in Pseudomonas
      aeruginosa strain BC15.
AB  - Cadmium (Cd) has been used extensively in metal plating, mining, paints and
      plastic generation etc. In this study, Cd resistance (cadR) gene was
      characterized from the environmental isolate Pseudomonas aeruginosa BC15. The
      cadR sequences showed high homology with P. aeruginosa FLH033011 (100%), P.
      aeruginosa PAO1 (99%), and P. aeruginosa UCBPP-PA14 (98%) respectively. Homology
      modeling of cadR was carried out by using swiss-prot server. Crystal structures
      of E. coli CueR for Cu (1q05) and ZntR (1q08) for Zn have been used as a
      template. The sequence identity of P. aeruginosa cadR shares 34% for CueR and 43%
      for ZntR. Fold recognition of P. aeruginosa cadR was created by using PHYRE web
      server. Transcriptional regulator CueR (1q06a) from E. coli was chosen as the
      template. CadR has 31% identity and the estimated precision was 100%. The cadR
      gene was cloned in pET30b and transformed into E. coli BL21. The molecular weight
      protein of cadR was estimated to be 25 kDa by SDS-PAGE. The recombinant E. coli
      cadR efficiently grow in the Cd supplemented LB medium and agar plate. The order
      of the resistance of E. coli cadR was Mn > Pb > Cu > Cd > Ni > Zn. These findings
      can lead to the use of P. aeruginosa BC15 for the remediation of Cd and other
      heavy metals present in the polluted environment.

PMID- 22467198
TI  - Donor information for living donor liver transplantation: where can comprehensive
      information be found?
AB  - Recently published data show that a large number of candidates for living donor
      liver transplantation (LDLT) actively look for additional information on the
      Internet because today it represents the main source of information for many of
      them. However, little is known about the quality of the information on LDLT
      available on the Internet. Our aim was, therefore, to comprehensively evaluate
      the online information available for LDLT candidates with the expanded Ensuring
      Quality Information for Patients (EQIP) tool (0-36 items). One hundred Web sites
      on LDLT were initially found with the Google, Bing, and Yahoo search engines, and
      we identified 32 Web sites that provided specific information for such candidates
      in English. Only 9 Web sites addressed >20 items and the scores tended to be
      higher for educational (P = 0.13) and scientific sites (P = 0.07) compared to
      hospital sites. The median number of items from the EQIP tool was only 16
      (interquartile range = 13-20), and quantitative postoperative morbidity and
      mortality risk estimates were available on only 19% and 44% of the Web sites,
      respectively, despite the idea of major complications being mentioned on most Web
      sites. This analysis demonstrated several significant shortcomings in the quality
      of the information provided to potential donors for LDLT according to the EQIP
      instrument. We conclude that there is an urgent need to produce a Web site
      compliant with international standards for the quality of donor information.

PMID- 22467199
TI  - Production of angiotensin-I-converting enzyme inhibitory peptides from beta
      lactoglobulin- and casein-derived peptides: an integrative approach.
AB  - Angiotensin I-converting enzyme (ACE) inhibition is one of the mechanisms by
      which reduction in blood pressure is exerted. Whey proteins are a rich source of
      ACE inhibitory peptides and have shown a blood pressure reduction effect i.e.
      antihypertensive activity. The aim of this work was to develop a simplified
      process using a combination of adsorption and microfiltration steps for the
      production of hydrolysates from whey with high ACE inhibitory activity and
      potency; the latter was measured as the IC50, which is the peptide concentration
      required to reduce ACE activity by half. This process integrates the selective
      separation of beta-lactoglobulin- and casein-derived peptides (CDP) from rennet
      whey and their hydrolysis, which results in partially pure, less complex
      hydrolysates with high bioactive potency. Hydrolysis was carried out with
      protease N "Amano" in a thermostatically controlled membrane reactor operated in
      a batch mode. By applying the integrative approach it was possible to produce
      from the same feedstock two different hydrolysates that exhibited high ACE
      inhibition. One hydrolysate was mainly composed of casein-derived peptides with
      IC50=285 MUg/mL. In this hydrolysate we identified the well-known potent ACE
      inhibitor and antihypertensive tripeptide Ile-Pro-Pro (IPP) and another novel
      octapeptide Gln-Asp-Lys-Thr-Glu-Ile-Pro-Thr (QDKTEIPT). The second hydrolysate
      was mainly composed of beta-lactoglobulin derived peptides with IC50=28 MUg/mL.
      This hydrolysate contained a tetrapeptide (Ile-Ile-Ala-Glu) IIAE as one of the
      two major peptides. A further advantage to this process is that enzyme activity
      was substantially increased as enzyme product inhibition was reduced.

PMID- 22467200
TI  - miR-93/Sp7 function loop mediates osteoblast mineralization.
AB  - microRNAs (miRNAs) play pivotal roles in osteoblast differentiation. However, the
      mechanisms of miRNAs regulating osteoblast mineralization still need further
      investigation. Here, we performed miRNA profiling and identified that miR-93 was
      the most significantly downregulated miRNA during osteoblast mineralization.
      Overexpression of miR-93 in cultured primary mouse osteoblasts attenuated
      osteoblast mineralization. Expression of the Sp7 transcription factor 7 (Sp7,
      Osterix), a zinc finger transcription factor and critical regulator of osteoblast
      mineralization, was found to be inversely correlated with miR-93. Then Sp7 was
      confirmed to be a target of miR-93. Overexpression of miR-93 in cultured
      osteoblasts reduced Sp7 protein expression without affecting its mRNA level.
      Luciferase reporter assay showed that miR-93 directly targeted Sp7 by
      specifically binding to the target coding sequence region (CDS) of Sp7.
      Experiments such as electrophoretic mobility shift assay (EMSA), chromatin
      immunoprecipitation (ChIP), and promoter luciferase reporter assay confirmed that
      Sp7 bound to the promoter of miR-93. Furthermore, overexpression of Sp7 reduced
      miR-93 transcription, whereas blocking the expression of Sp7 promoted miR-93
      transcription. Our study showed that miR-93 was an important regulator in
      osteoblast mineralization and miR-93 carried out its function through a novel miR
      93/Sp7 regulatory feedback loop. Our findings provide new insights into the roles
      of miRNAs in osteoblast mineralization.

PMID- 22467201
TI  - Effect of some pyrimidine compounds on rat brain monoamine oxidase-B in vitro.
AB  - The effects of some pyrimidine compounds (PCs) including barbituric acid (BA) 5,5
      diethyl barbituric acid (DEBA), 2-thiobarbituric acid (TBA), violuric acid (VA),
      2-thiouracil (TU), and 6-amino-2-thiouracil (ATU) on the activity of rat brain
      monoamine oxidase-B (MAO-B) were investigated. The results revealed that MAO-B
      was activated by BA, DEBA, TBA, TU, and ATU, and the activation was structural,
      concentration, and time dependent. However, MAO-B was inhibited by VA in a
      noncompetitive and irreversible manner with an enzyme-inhibitor dissociation
      constant (K (i) value) of 32 nM and IC(50) equals to 19 nM. All the studied PCs
      changed both the optimum pH and temperature of MAO-B.

PMID- 22467202
TI  - The weak relationship between anatomy competence and clinical skills in junior
      medical students.
AB  - In modern curricula, the early integration of anatomy and clinical skills
      education at undergraduate level is seen as important. However, the direct
      relationship between medical students' competence in anatomy, and their clinical
      proficiency during early undergraduate years, has scarcely been studied. In this
      study, the marks for anatomy and clinical skills of three consecutive cohorts of
      medical students (n = 538 in total) during their first two years were correlated.
      The anatomy competence was measured using a new marker, the Anatomy Competence
      Score (ACS) which was calculated with equal contributions from theory knowledge
      and its practical and clinical application. Proficiency in clinical skills was
      determined by OSCE performance marks for stations which examined physical
      examination and practical procedural skills. The possible compounding effect of
      students' general academic ability was investigated by using the overall
      performance mark for each student based on their performance in all subjects over
      the first two years of the medical curriculum. We found that the correlation
      between anatomy and clinical skills marks was weak to moderate. However, this
      correlation was virtually nullified once the effect of academic ability was
      accounted for. Although these findings suggest that anatomy education does not
      compliment early clinical education, the lack of complexity of clinical problems
      used in clinical skills assessments (OSCEs) during the early stages may well be
      the primary contributing factor to this finding.

PMID- 22467204
TI  - Chiral electrostatics breaks the mirror symmetry of DNA supercoiling.
AB  - DNA supercoiling plays a fundamental role in regulating cellular activity and in
      the packaging of genetic material. In this communication, we analyse the effect
      of attractive chiral forces on the conformation of a closed circular DNA
      molecule, arising due to the helical patterns of charges on the DNA. We propose a
      model for closed loop DNA which uses the results of the recent theory of
      electrostatic interactions of a braid of two free-ended DNA molecules. Our model
      reproduces the known features of DNA supercoiling in an environment of low ionic
      strength. In high salt conditions, and in the presence of counterions that have
      high affinity to the DNA grooves, helix-specific forces significantly affect the
      conformation of the molecule by favouring a state characterized by a central left
      handed braided section where there is close contact between distant portions of
      the loop. In such an environment we predict a previously unexplored possibility
      that nicked or topologically relaxed DNA molecules adopt a writhed state. This
      prediction suggests an alternative explanation for experiments in which it was
      assumed that the most stable topoisomer is always an open circle. Our results
      also give the first plausible explanation for the occurrence of tightly
      interwound molecules observed in cryo-electron microscopy and atomic force
      microscopy in a high ionic strength environment. We suggest several new
      experiments to test the predictions of this theory.

PMID- 22467203
TI  - Diagnosis of occupational asthma: an update.
AB  - Work-related asthma (WRA) includes patients with sensitizer- and/or irritant
      induced asthma in the workplace, as well as patients with preexisting asthma that
      is worsened by work factors. WRA is underdiagnosed; thus, the diagnosis is
      critical to prevent disease progression and its potential for morbidity and
      mortality. The interview is the first diagnostic tool to be used by physicians,
      and the question, "Does asthma improve away from work?" is of the highest
      sensitivity. However, history can show numerous false positives, and the
      relationships between asthma worsening and work should be confirmed by objective
      methods such as peak expiratory flow (PEF) at and away from work. PEF sensitivity
      and specificity can be enhanced in combination with nonspecific bronchial
      hyperresponsiveness to histamine/methacholine (NSBP) before and after 2 weeks at
      work and a similar period off work. Immunologic testing, especially skin prick
      test (SPT) or specific IgE, is useful for high molecular weight allergens and
      some low molecular weight agents. Other immunologic tests, as well as induced
      sputum, measurement of exhaled nitric oxide, exhaled breath condensate, and
      specific inhalation challenge (SIC) are methods that contribute to the diagnosis
      and are typically performed at specialized facilities. A diagnosis of
      occupational asthma (OA) should no longer be based on a compatible history only
      but should be confirmed by means of objective testing. SIC is the diagnostic gold
      standard. When SIC is not available, the combination of PEF measurement, NSBP
      test , a specific SPT, or specific IgE may be an appropriate alternative in
      diagnosing OA.

PMID- 22467205
TI  - Yields of damage to C4' deoxyribose and to pyrimidines in pUC18 by the direct
      effect of ionizing radiation.
AB  - Our mechanistic understanding of damage formation in DNA by the direct effect
      relies heavily on what is known of free radical intermediates studied by EPR
      spectroscopy. Bridging this information to stable product formation requires
      methods with comparable sensitivities, a criterion met by the (32)P-post-labeling
      assay developed by Weinfeld and Soderlind, [Weinfeld,M. and Soderlind,K.-J.M.
      (1991) (32)P-Postlabeling detection of radiation-induced DNA damage:
      identification and estimation of thymine glycols and phosphoglycolate termini.
      Biochemistry, 30, 1091-1097] which when applied to the indirect effect, detected
      phosphoglycolate (pg) and thymine glycol (Tg). Here we applied this assay to the
      direct effect, measuring product yields in pUC18 films with hydration levels
      (Gamma) of 2.5, 16 or 23 waters per nucleotide and X-irradiated at either 4 K or
      room temperature (RT). The yields of pg [G(pg)] for Gamma ~ 2.5 were 2.8 +/- 0.2
      nmol/J (RT) and 0.2 +/- 0.3 nmol/J (4 K), which is evidence that the C4' radical
      contributes little to the total deoxyribose damage via the direct effect. The
      yield of detectable base damage [G(B*)] at Gamma ~ 2.5 was found to be 30.2 +/-
      1.0 nmol/J (RT) and 12.9 +/- 0.7 nmol/J (4 K). While the base damage called B*,
      could be due to either oxidation or reduction, we argue that two reduction
      products, 5,6-dihydrouracil and 5,6-dihydrothymine, are the most likely
      candidates.

PMID- 22467206
TI  - Identification of allele-specific alternative mRNA processing via transcriptome
      sequencing.
AB  - Establishing the functional roles of genetic variants remains a significant
      challenge in the post-genomic era. Here, we present a method, allele-specific
      alternative mRNA processing (ASARP), to identify genetically influenced mRNA
      processing events using transcriptome sequencing (RNA-Seq) data. The method
      examines RNA-Seq data at both single-nucleotide and whole-gene/isoform levels to
      identify allele-specific expression (ASE) and existence of allele-specific
      regulation of mRNA processing. We applied the methods to data obtained from the
      human glioblastoma cell line U87MG and primary breast cancer tissues and found
      that 26-45% of all genes with sufficient read coverage demonstrated ASE, with
      significant overlap between the two cell types. Our methods predicted potential
      mechanisms underlying ASE due to regulations affecting either whole-gene-level
      expression or alternative mRNA processing, including alternative splicing,
      alternative polyadenylation and alternative transcriptional initiation. Allele
      specific alternative splicing and alternative polyadenylation may explain ASE in
      hundreds of genes in each cell type. Reporter studies following these predictions
      identified the causal single nucleotide variants (SNVs) for several allele
      specific alternative splicing events. Finally, many genes identified in our study
      were also reported as disease/phenotype-associated genes in genome-wide
      association studies. Future applications of our approach may provide ample
      insights for a better understanding of the genetic basis of gene regulation
      underlying phenotypic diversity and disease mechanisms.

PMID- 22467207
TI  - The chromatin remodeling and mRNA splicing functions of the Brahma (SWI/SNF)
      complex are mediated by the SNR1/SNF5 regulatory subunit.
AB  - Nucleosome remodeling catalyzed by the ATP-dependent SWI/SNF complex is essential
      for regulated gene expression. Transcriptome profiling studies in flies and
      mammals identified cell cycle and hormone responsive genes as important targets
      of remodeling complex activities. Loss of chromatin remodeling function has been
      linked to developmental abnormalities and aggressive cancers. The Drosophila
      Brahma (Brm) SWI/SNF complex assists in reprogramming and coordinating gene
      expression in response to ecdysone hormone signaling at critical points during
      development. We used RNAi knockdown in cultured cells and transgenic flies, and
      conditional mutant alleles to identify unique and important functions of two
      conserved Brm complex core subunits, SNR1/SNF5 and BRM/SNF2-SWI2, on target gene
      regulation. Unexpectedly, we found that incorporation of a loss of function SNR1
      subunit led to alterations in RNA polymerase elongation, pre-mRNA splicing
      regulation and chromatin accessibility of ecdysone hormone regulated genes,
      revealing that SNR1 functions to restrict BRM-dependent nucleosome remodeling
      activities downstream of the promoter region. Our results reveal critically
      important roles of the SNR1/SNF5 subunit and the Brm chromatin remodeling complex
      in transcription regulation during elongation by RNA Polymerase II and completion
      of pre-mRNA transcripts that are dependent on hormone signaling in late
      development.

PMID- 22467208
TI  - Real-time single-molecule tethered particle motion experiments reveal the
      kinetics and mechanisms of Cre-mediated site-specific recombination.
AB  - Tyrosine family recombinases (YRs) are widely utilized in genome engineering
      systems because they can easily direct DNA rearrangement. Cre recombinases, one
      of the most commonly used types of YRs, catalyze site-specific recombination
      between two loxP sites without the need for high-energy cofactors, other
      accessory proteins or a specific DNA target sequence between the loxP sites.
      Previous structural, analytical ultracentrifuge and electrophoretic analyses have
      provided details of the reaction kinetics and mechanisms of Cre recombinase
      activity; whether there are reaction intermediates or side pathways involved has
      been left unaddressed. Using tethered particle motion (TPM), the Cre-mediated
      site-specific recombination process has been delineated, from beginning to end,
      at the single-molecule level, including the formation of abortive complexes and
      wayward complexes blocking inactive nucleoprotein complexes from entering the
      recombination process. Reversibility in the strand-cleavage/-ligation process and
      the formation of a thermally stable Holliday junction intermediate were observed
      within the Cre-mediated site-specific recombination process. Rate constants for
      each elementary step, which explain the overall reaction outcomes under various
      conditions, were determined. Taking the findings of this study together, they
      demonstrate the potential of single-molecule methodology as an alternative
      approach for exploring reaction mechanisms in detail.

PMID- 22467209
TI  - Chromosomal context and epigenetic mechanisms control the efficacy of genome
      editing by rare-cutting designer endonucleases.
AB  - The ability to specifically engineer the genome of living cells at precise
      locations using rare-cutting designer endonucleases has broad implications for
      biotechnology and medicine, particularly for functional genomics, transgenics and
      gene therapy. However, the potential impact of chromosomal context and
      epigenetics on designer endonuclease-mediated genome editing is poorly
      understood. To address this question, we conducted a comprehensive analysis on
      the efficacy of 37 endonucleases derived from the quintessential I-CreI
      meganuclease that were specifically designed to cleave 39 different genomic
      targets. The analysis revealed that the efficiency of targeted mutagenesis at a
      given chromosomal locus is predictive of that of homologous gene targeting.
      Consequently, a strong genome-wide correlation was apparent between the
      efficiency of targeted mutagenesis (<= 0.1% to ~ 6%) with that of homologous gene
      targeting (<= 0.1% to ~ 15%). In contrast, the efficiency of targeted mutagenesis
      or homologous gene targeting at a given chromosomal locus does not correlate with
      the activity of individual endonucleases on transiently transfected substrates.
      Finally, we demonstrate that chromatin accessibility modulates the efficacy of
      rare-cutting endonucleases, accounting for strong position effects. Thus,
      chromosomal context and epigenetic mechanisms may play a major role in the
      efficiency rare-cutting endonuclease-induced genome engineering.

PMID- 22467210
TI  - H2A.Z.2.2 is an alternatively spliced histone H2A.Z variant that causes severe
      nucleosome destabilization.
AB  - The histone variant H2A.Z has been implicated in many biological processes, such
      as gene regulation and genome stability. Here, we present the identification of
      H2A.Z.2.2 (Z.2.2), a novel alternatively spliced variant of histone H2A.Z and
      provide a comprehensive characterization of its expression and chromatin
      incorporation properties. Z.2.2 mRNA is found in all human cell lines and tissues
      with highest levels in brain. We show the proper splicing and in vivo existence
      of this variant protein in humans. Furthermore, we demonstrate the binding of
      Z.2.2 to H2A.Z-specific TIP60 and SRCAP chaperone complexes and its active
      replication-independent deposition into chromatin. Strikingly, various
      independent in vivo and in vitro analyses, such as biochemical fractionation,
      comparative FRAP studies of GFP-tagged H2A variants, size exclusion
      chromatography and single molecule FRET, in combination with in silico molecular
      dynamics simulations, consistently demonstrate that Z.2.2 causes major structural
      changes and significantly destabilizes nucleosomes. Analyses of deletion mutants
      and chimeric proteins pinpoint this property to its unique C-terminus. Our
      findings enrich the list of known human variants by an unusual protein belonging
      to the H2A.Z family that leads to the least stable nucleosome known to date.

PMID- 22467211
TI  - PAREsnip: a tool for rapid genome-wide discovery of small RNA/target interactions
      evidenced through degradome sequencing.
AB  - Small RNAs (sRNAs) are a class of short (20-25 nt) non-coding RNAs that play
      important regulatory roles in gene expression. An essential first step in
      understanding their function is to confidently identify sRNA targets. In plants,
      several classes of sRNAs such as microRNAs (miRNAs) and trans-acting small
      interfering RNAs have been shown to bind with near-perfect complementarity to
      their messenger RNA (mRNA) targets, generally leading to cleavage of the mRNA.
      Recently, a high-throughput technique known as Parallel Analysis of RNA Ends
      (PARE) has made it possible to sequence mRNA cleavage products on a large-scale.
      Computational methods now exist to use these data to find targets of conserved
      and newly identified miRNAs. Due to speed limitations such methods rely on the
      user knowing which sRNA sequences are likely to target a transcript. By limiting
      the search to a tiny subset of sRNAs it is likely that many other sRNA/mRNA
      interactions will be missed. Here, we describe a new software tool called
      PAREsnip that allows users to search for potential targets of all sRNAs obtained
      from high-throughput sequencing experiments. By searching for targets of a
      complete 'sRNAome' we can facilitate large-scale identification of sRNA targets,
      allowing us to discover regulatory interaction networks.

PMID- 22467212
TI  - Genome-wide profiles of H2AX and gamma-H2AX differentiate endogenous and
      exogenous DNA damage hotspots in human cells.
AB  - Phosphorylation of the histone variant H2AX forms gamma-H2AX that marks DNA
      double-strand break (DSB). Here, we generated the sequencing-based maps of H2AX
      and gamma-H2AX positioning in resting and proliferating cells before and after
      ionizing irradiation. Genome-wide locations of possible endogenous and exogenous
      DSBs were identified based on gamma-H2AX distribution in dividing cancer cells
      without irradiation and that in resting cells upon irradiation, respectively.
      gamma-H2AX-enriched regions of endogenous origin in replicating cells included
      sub-telomeres and active transcription start sites, apparently reflecting
      replication- and transcription-mediated stress during rapid cell division.
      Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at
      these endogenous hotspots. This phenomenon was only observed in dividing cancer
      cells but not in resting cells. Endogenous H2AX was concentrated on the
      transcription start site of actively transcribed genes but was irrelevant to
      pausing of RNA polymerase II (pol II), which precisely coincided with gamma-H2AX
      of endogenous origin. gamma-H2AX enrichment upon irradiation also coincided with
      actively transcribed regions, but unlike endogenous gamma-H2AX, it extended into
      the gene body and was not specifically concentrated on the pausing site of pol
      II. Sub-telomeres were less responsive to external DNA damage than to endogenous
      stress. Our findings provide insight into DNA repair programs of cancer and may
      have implications for cancer therapy.

PMID- 22467213
TI  - Analysis of C. elegans intestinal gene expression and polyadenylation by
      fluorescence-activated nuclei sorting and 3'-end-seq.
AB  - Despite the many advantages of Caenorhabditis elegans, biochemical approaches to
      study tissue-specific gene expression in post-embryonic stages are challenging.
      Here, we report a novel experimental approach for efficient determination of
      tissue-specific transcriptomes involving the rapid release and purification of
      nuclei from major tissues of post-embryonic animals by fluorescence-activated
      nuclei sorting (FANS), followed by deep sequencing of linearly amplified 3'-end
      regions of transcripts (3'-end-seq). We employed these approaches to compile the
      transcriptome of the developed C. elegans intestine and used this to analyse
      tissue-specific cleavage and polyadenylation. In agreement with intestinal
      specific gene expression, highly expressed genes have enriched GATA-elements in
      their promoter regions and their functional properties are associated with
      processes that are characteristic for the intestine. We systematically mapped pre
      mRNA cleavage and polyadenylation sites, or polyA sites, including more than 3000
      sites that have previously not been identified. The detailed analysis of the 3'
      ends of the nuclear mRNA revealed widespread alternative polyA site use (APA) in
      intestinally expressed genes. Importantly, we found that intestinal polyA sites
      that undergo APA tend to have U-rich and/or A-rich upstream auxiliary elements
      that may contribute to the regulation of 3'-end formation in the intestine.

PMID- 22467214
TI  - TricycloDNA-modified oligo-2'-deoxyribonucleotides reduce scavenger receptor B1
      mRNA in hepatic and extra-hepatic tissues--a comparative study of oligonucleotide
      length, design and chemistry.
AB  - We report the evaluation of 20-, 18-, 16- and 14-mer phosphorothioate (PS)
      modified tricycloDNA (tcDNA) gapmer antisense oligonucleotides (ASOs) in T(m),
      cell culture and animal experiments and compare them to their gap-matched 20-mer
      2'-O-methoxyethyl (MOE) and 14-mer 2',4'-constrained ethyl (cEt) counterparts.
      The sequence-matched 20-mer tcDNA and MOE ASOs showed similar T(m) and activity
      in cell culture under free-uptake and cationic lipid-mediated transfection
      conditions, while the 18-, 16- and 14-mer tcDNA ASOs were moderate to
      significantly less active. These observations were recapitulated in the animal
      experiments where the 20-mer tcDNA ASO formulated in saline showed excellent
      activity (ED(50) 3.9 mg/kg) for reducing SR-B1 mRNA in liver. The tcDNA 20-mer
      ASO also showed better activity than the MOE 20-mer in several extra-hepatic
      tissues such as kidney, heart, diaphragm, lung, fat, gastrocnemius and
      quadriceps. Interestingly, the 14-mer cEt ASO showed the best activity in the
      animal experiments despite significantly lower T(m) and 5-fold reduced activity
      in cell culture relative to the 20-mer tcDNA and MOE-modified ASOs. Our
      experiments establish tcDNA as a useful modification for antisense therapeutics
      and highlight the role of chemical modifications in influencing ASO pharmacology
      and pharmacokinetic properties in animals.

PMID- 22467215
TI  - Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA
      aptamers.
AB  - Human epidermal growth factor receptor 2 (HER2) expression in breast cancer is
      associated with an aggressive phenotype and poor prognosis, making it an
      appealing therapeutic target. Trastuzumab, an HER2 antibody-based inhibitor, is
      currently the leading targeted treatment for HER2(+)-breast cancers.
      Unfortunately, many patients inevitably develop resistance to the therapy,
      highlighting the need for alternative targeted therapeutic options. In this
      study, we used a novel, cell-based selection approach for isolating 'cell-type
      specific', 'cell-internalizing RNA ligands (aptamers)' capable of delivering
      therapeutic small interfering RNAs (siRNAs) to HER2-expressing breast cancer
      cells. RNA aptamers with the greatest specificity and internalization potential
      were covalently linked to siRNAs targeting the anti-apoptotic gene, Bcl-2. We
      demonstrate that, when applied to cells, the HER2 aptamer-Bcl-2 siRNA conjugates
      selectively internalize into HER2(+)-cells and silence Bcl-2 gene expression.
      Importantly, Bcl-2 silencing sensitizes these cells to chemotherapy (cisplatin)
      suggesting a potential new therapeutic approach for treating breast cancers with
      HER2(+)-status. In summary, we describe a novel cell-based selection methodology
      that enables the identification of cell-internalizing RNA aptamers for targeting
      therapeutic siRNAs to HER2-expressing breast cancer cells. The future refinement
      of this technology may promote the widespread use of RNA-based reagents for
      targeted therapeutic applications.

PMID- 22467217
TI  - [Health of immigrant population of consultants at the Baudelaire outpatient
      clinic in Saint-Antoine hospital in Paris, France].
AB  - Social and health data on the immigrant population remain scarce in France,
      especially concerning those in irregular situation. The Baudelaire outpatient
      clinic in Saint- Antoine hospital in Paris (PASS, i.e. specific free medicosocial
      care for the poor, the uninsured or the undocumented patients) treats a majority
      of immigrants, a lot of them being in an irregular residence status. The
      objectives of this study were to describe the social and health status of the
      immigrant consultants, to compare regular and undocumented migrants and to
      describe their main reasons for migration. A cross-sectional, descriptive, survey
      among the immigrant consultants has been performed among this outpatient clinic
      in April and May 2009. In total, 536 patients were included. Their age mean was
      45 years, 62% are male, 49% are in an irregular situation and they have been in
      France for 12 years in average (19 years for the regular immigrants and 5 years
      for the undocumented). More than 20% had no health insurance. A majority (55%) of
      patients were suffering from a chronic disease. The more frequent ones were
      hypertension (20%), type 2 diabetes (11.6%), chronic infectious diseases - HIV,
      HBV, HCV - (7%). Reasons for immigration were mostly economical (39%), family
      (19%) and political (17%). Health reasons were at the 4th rank and concerned 9%
      of the patients. The main chronic diseases observed among this population are
      similar to those of the general population of consultants in primary health care,
      except for the chronic infectious diseases, which are more frequent. Immigration
      for health reasons represents only a small proportion of all immigration reasons.
      For this population, free clinics like the one investigated here constitute
      unique, irreplaceable, access points in the French healthcare system.

PMID- 22467218
TI  - Growth hormone synergizes with BMP9 in osteogenic differentiation by activating
      the JAK/STAT/IGF1 pathway in murine multilineage cells.
AB  - Growth hormone (GH) is usually released by somatotrophs in the anterior pituitary
      in response to the GH-releasing hormone and plays an important role in skeleton
      development and postnatal growth. However, it is unclear if extrapituitary GH
      exerts any effect on murine multilineage cells (MMCs). MMCs are multipotent
      progenitors that give rise to several lineages, including bone, cartilage, and
      fat. We have identified bone morphogenic protein 9 (BMP9) as one of the most
      osteogenic BMPs in MMCs by regulating a distinct set of downstream mediators. In
      this study, we find that GH is one of the most significantly upregulated genes by
      BMP9 in mouse MMCs through expression-profiling analysis. We confirm that GH is a
      direct early target of and upregulated by BMP9 signaling. Exogenous GH synergizes
      with BMP9 on inducing early and late osteogenic markers in MMCs. Furthermore,
      BMP9 and GH costimulation leads to a significant expansion of growth plate in
      cultured limb explants. Although GH alone does not induce de novo bone formation
      in an ectopic bone formation model, BMP9 and GH costimulated MMCs form more
      mature bone, which can be inhibited by silencing GH expression. The synergistic
      osteogenic activity between BMP9 and GH can be significantly blunted by JAK/STAT
      inhibitors, leading to a decrease in GH-regulated insulin-like growth factor 1
      (IGF1) expression in MMCs. Our results strongly suggest that BMP9 may effectively
      regulate extrapituitary GH expression in MMCs. Thus, it is conceivable that the
      BMP9-GH-IGF axis may be exploited as an innovative strategy to enhance
      osteogenesis in regenerative medicine.

PMID- 22467219
TI  - Detection and characterization of subvisible aggregates of monoclonal IgG in
      serum.
AB  - PURPOSE: To detect and characterize the aggregation of therapeutic monoclonal
      antibodies in undiluted biological fluids. METHODS: Fluorescently labeled
      subvisible IgG aggregates formed by applying either heat stress or by pH-shift
      were investigated immediately after addition to human serum, and after 24 h.
      Unstressed and stressed IgG formulations were analyzed by fluorescence single
      particle tracking, confocal laser scanning microscopy and flow cytometry.
      RESULTS: Unstressed formulations remained free from subvisible aggregates in
      serum, whereas heat-stressed and pH-shift stressed formulations showed dissimilar
      aggregation behaviors. The aggregation profile of the heat-stressed formulation
      diluted in serum remained practically the same as the one diluted in buffer, even
      after the 24 h incubation period. The pH-shift stressed formulation had
      strikingly smaller and more numerous subvisible aggregates immediately after
      dilution in serum compared to buffer. These aggregates became noticeably larger
      in both diluents after 24 h, but in serum they appeared to be formed by other
      types of constituents than the labeled protein itself. CONCLUSION: These results
      show that subvisible therapeutic protein aggregates may undergo changes in
      number, type and size distribution upon contact with human serum. This emphasizes
      the importance of analytical strategies for monitoring aggregation in undiluted
      biological fluids.

PMID- 22467220
TI  - The importance of mitochondrial metabolic activity and mitochondrial DNA
      replication during oocyte maturation in vitro on oocyte quality and subsequent
      embryo developmental competence.
AB  - Mitochondrial metabolic capacity and DNA replication have both been shown to
      affect oocyte quality, but it is unclear which one is more critical. In this
      study, immature oocytes were treated with FCCP or ddC to independently inhibit
      the respective mitochondrial metabolic capacity or DNA replication of oocytes
      during in vitro maturation. To differentiate their roles, we evaluated various
      parameters related to oocyte maturation (germinal vesicle break down and nuclear
      maturation), quality (spindle formation, chromosome alignment, and mitochondrial
      distribution pattern), fertilization capability, and subsequent embryo
      developmental competence (blastocyst formation and cell number of blastocyst).
      Inhibition of mitochondrial metabolic capacity with FCCP resulted in a reduced
      percent of oocytes with nuclear maturation; normal spindle formation and
      chromosome alignment; evenly distributed mitochondria; and an ability to form
      blastocysts. Inhibition of mtDNA replication with ddC has no detectable effect on
      oocyte maturation and mitochondrial distribution, although high-dose ddC
      increased the percent of oocytes showing abnormal spindle formation and
      chromosome alignment. ddC did, however, reduce blastocyst formation
      significantly. Neither FCCP nor ddC exposure had an effect on the rate of
      fertilization. These findings suggest that the effects associated with lower
      mitochondrial DNA copy number do not coincide with the effects seen with reduced
      mitochondrial metabolic activity in oocytes. Inhibiting mitochondrial metabolic
      activity during oocyte maturation has a negative impact on oocyte maturation and
      subsequent embryo developmental competence. A reduction in mitochondrial DNA copy
      number, on the other hand, mainly affects embryonic development potential, but
      has little effect on oocyte maturation and in vitro fertilization.

PMID- 22467216
TI  - Homologous recombination and its regulation.
AB  - Homologous recombination (HR) is critical both for repairing DNA lesions in
      mitosis and for chromosomal pairing and exchange during meiosis. However, some
      forms of HR can also lead to undesirable DNA rearrangements. Multiple regulatory
      mechanisms have evolved to ensure that HR takes place at the right time, place
      and manner. Several of these impinge on the control of Rad51 nucleofilaments that
      play a central role in HR. Some factors promote the formation of these structures
      while others lead to their disassembly or the use of alternative repair pathways.
      In this article, we review these mechanisms in both mitotic and meiotic
      environments and in different eukaryotic taxa, with an emphasis on yeast and
      mammal systems. Since mutations in several proteins that regulate Rad51
      nucleofilaments are associated with cancer and cancer-prone syndromes, we discuss
      how understanding their functions can lead to the development of better tools for
      cancer diagnosis and therapy.

PMID- 22467221
TI  - Integrated high pressure microhydraulic actuation and control for surgical
      instruments.
AB  - To reduce the surgical trauma to the patient, minimally invasive surgery is
      gaining considerable importance since the eighties. More recently, robot assisted
      minimally invasive surgery was introduced to enhance the surgeon's performance in
      these procedures. This resulted in an intensive research on the design,
      fabrication and control of surgical robots over the last decades. A new
      development in the field of surgical tool manipulators is presented in this
      article: a flexible manipulator with distributed degrees of freedom powered by
      microhydraulic actuators. The tool consists of successive flexible segments, each
      with two bending degrees of freedom. To actuate these compliant segments,
      dedicated fluidic actuators are incorporated, together with compact hydraulic
      valves which control the actuator motion. Especially the development of
      microvalves for this application was challenging, and are the main focus of this
      paper. The valves distribute the hydraulic power from one common high pressure
      supply to a series of artificial muscle actuators. Tests show that the angular
      stroke of the each segment of this medical instrument is 90 degrees .

PMID- 22467222
TI  - Response to "MHC-dependent mate choice in humans: Why genomic patterns from the
      HapMap European American data set support the hypothesis". HapMap genotypes do
      not confidently support a role for the MHC locus in human mate selection.

PMID- 22467224
TI  - Primary hyperparathyroidism associated with ulcerative colitis.

PMID- 22467223
TI  - High-efficiency, microscale GaN light-emitting diodes and their thermal
      properties on unusual substrates.
AB  - A method for forming efficient, ultrathin GaN light-emitting diodes (LEDs) and
      for their assembly onto foreign substances is reported. The LEDs have lateral
      dimensions ranging from ~1 mm * 1 mm to ~25 MUm * 25 MUm. Quantitative
      experimental and theoretical studies show the benefits of small device geometry
      on thermal management, for both continuous and pulsed-mode operation, the latter
      of which suggests the potential use of these technologies in bio-integrated
      contexts.

PMID- 22467226
TI  - The tyranny of but.

PMID- 22467225
TI  - Radon testing and mitigation: an intervention in a primary care setting.
AB  - Radon is the second leading cause of lung cancer and it is recommended that all
      homes be tested for radon. Written surveys completed by 692 patients at two
      primary care clinics in the Minneapolis, MN, area revealed that only 24.7 % had
      ever tested their home. Testing rate was higher with greater income and education
      level and in homes without someone who smokes. Of participants whose homes had
      not been tested, 250 were enrolled in an intervention that included printed
      information on radon, a coupon for a discounted testing kit, and encouragement by
      their primary care provider to test. Follow-up indicated minimal effect of this
      intervention, with only 14.4 % of these participants testing during the ensuing
      year. Future studies should assess a stronger intervention, perhaps over multiple
      visits, and providing test kits on site. Targeting patients who smoke may be an
      effective use of resources.

PMID- 22467227
TI  - Prevalence and clinical outcomes of the 46/1 haplotype, Janus kinase 2 mutations,
      and ten-eleven translocation 2 mutations in Budd-Chiari syndrome and their impact
      on thrombotic complications post liver transplantation.
AB  - Latent myeloproliferative disorders (MPDs) can be identified by Janus kinase 2
      (JAK2) mutations in patients with idiopathic Budd-Chiari syndrome (BCS). The
      incidence and clinical outcomes of JAK2 mutations, novel ten-eleven translocation
      2 (TET2) mutations, and the 46/1 haplotype in BCS are unknown for liver
      transplantation (LT). We undertook molecular studies of 66 patients presenting
      with BCS and correlated the results with the clinical outcomes. An overt MPD was
      present in 20% of the cases, and a latent MPD confirmed by the presence of a JAK2
      mutation was detected in 45%. Testing for a TET2 mutation identified MPDs at the
      molecular level in another 7% of the subset of patients with BCS who were
      evaluated. The 46/1 haplotype frequency was significantly greater in BCS patients
      versus the general population (P < 0.001). The presence of JAK2 and TET2
      mutations had no impact on 1-year survival. Thirty-six patients underwent LT, and
      12 developed liver-related thrombotic complications (33%). Ten of these 12
      patients required retransplantation. Retransplantation was more likely in those
      patients who developed liver-related thrombotic complications (P < 0.001). A JAK2
      mutation was highly associated with the development of thrombotic complications
      after LT (P = 0.005). In conclusion, the presence of JAK2V617F predicts hepatic
      and extrahepatic thrombotic complications after LT. Testing for TET2 mutations
      can identify another 7% of idiopathic BCS patients with molecular MPDs.

PMID- 22467228
TI  - Identifying bottlenecks in transient and stable production of recombinant
      monoclonal-antibody sequence variants in Chinese hamster ovary cells.
AB  - The increasing demand for antibody-based therapeutics has emphasized the need for
      technologies to improve recombinant antibody titers from mammalian cell lines.
      Moreover, as antibody therapeutics address an increasing spectrum of indications,
      interest has increased in antibody engineering to improve affinity and biological
      activity. However, the cellular mechanisms that dictate expression and the
      relationships between antibody sequence and expression level remain poorly
      understood. Fundamental understanding of how mammalian cells handle high levels
      of transgene expression and of the relationship between sequence and expression
      are vital to the development of new antibodies and for increasing recombinant
      antibody titers. In this work, we analyzed a pair of mutants that vary by a
      single amino acid at Kabat position 49 (heavy-chain framework), resulting in
      differential transient and stable titers with no apparent loss of antigen
      affinity. Through analysis of mRNA, gene copy number, intracellular antibody
      content, and secreted antibody, we found that while translational/post
      translational mechanisms are limiting in transient systems, it appears that the
      amount of available transgenic mRNA becomes the limiting event on stable
      integration of the recombinant genes. We also show that amino acid substitution
      at residue 49 results in production of a non-secreted HC variant and postulate
      that stable antibody expression is maintained at a level which prevents toxic
      accumulation of this HC-related protein. This study highlights the need for
      proper sequence engineering strategies when developing therapeutic antibodies and
      alludes to the early analysis of transient expression systems to identify the
      potential for aberrant stable expression behavior.

PMID- 22467229
TI  - Laryngeal support device enhances the learning of laryngeal anatomy and voice
      physiology.
AB  - Multidisciplinary cooperation in health care requires a solid knowledge in the
      basic sciences for a common ground of communication. In speech pathology, these
      fundamentals improve the accuracy of descriptive diagnoses and support the
      development of new therapeutic techniques and strategies. The aim of this study
      is to briefly discuss the benefits of hands-on education on laryngeal anatomy and
      voice physiology in Brazilian graduate programs in speech pathology, as well as
      to describe a simple prototype that can be used as a useful educational tool for
      this purpose. The laryngeal anatomic support device was designed to provide a
      vertical frame to hold human or mammalian larynges with no preservation
      treatment, with the goal of allowing good visualization of the vocal folds during
      artificial phonation. The device was designed to provide the user the ability to
      manipulate the soft and cartilaginous structures of the larynx with near-natural
      biomechanical properties. The description of the project is detailed to allow the
      reproduction of this simple and inexpensive device. It may be used as an
      experimental feature in a variety of settings, from high-school programs to
      experimental research methods, and may suit a wide array of different educational
      models.

PMID- 22467230
TI  - Prediction of central lymph node metastasis from papillary thyroid microcarcinoma
      by 18F-fluorodeoxyglucose PET/CT and ultrasonography.
AB  - PURPOSE: The presence of central lymph node (LN) metastasis increases the risk of
      cervical LN recurrence or distant metastasis in patients with papillary thyroid
      microcarcinoma (PTMC). We investigated the value of preoperative (18)F-fluoro-2
      deoxy-D-glucose-positron emission tomography (FDG PET)-computerized tomography
      (CT) and ultrasonography (US) to predict central LN metastasis from PTMC.
      PATIENTS AND METHODS: Two hundred patients with newly diagnosed unifocal PTMC
      were enrolled. Preoperative FDG PET-CT was performed, and the highest SUV
      (SUV(max)) of focally increased uptake at thyroid was measured. Tumor size was
      measured using preoperative US. Uni- and multivariate analyses were performed
      using the presence of focally increased uptake at thyroid (FDG positivity),
      SUV(max), tumor size, and clinical risk factor for central LN metastasis. ROC
      curves for risk factors were then analyzed. These analyses were undertaken in two
      groups: the all patients group and the FDG-positive group. Finally, we combined
      risk factors associated with central LN metastasis to improve predictive
      accuracy. RESULTS: Tumor size >6 mm was associated with central LN metastasis.
      FDG positivity was identified in 110 patients (55.0%) and the SUV(max) ranged
      from 1.8 to 12.8 (median 3.0). In FDG-positive group, SUV(max) >2.8 was
      associated with central LN metastasis. Addition of SUV(max) >2.8 to size >6 mm of
      PTMC improved sensitivity of predicting central LN metastasis from 55.0 to 67.5%,
      while specificity remained at 70.6%. CONCLUSION: Both FDG PET-CT and US are
      valuable for preoperative prediction of central LN metastasis from PTMC. Combined
      use of SUV(max) and tumor size improves sensitivity without changing specificity.

PMID- 22467231
TI  - Pesticide pressure and fish farming in barrage pond in northeastern France. Part
      III: how management can affect pesticide profiles in edible fish?
AB  - PURPOSE: The quality of fish produced in ponds needs to be ensured. Indeed, pond
      is often strongly connected to an agricultural watershed, and pesticides are a
      main health and environmental issue of concern. In this context, the purpose of
      this study is to highlight the management practices which could impact the
      pesticide contamination profiles in edible fish and to give recommendations for
      better practices. METHODS: A principal component analysis, coupled to a
      hierarchical cluster analysis, was performed to evaluate temporal evolution of
      contamination profiles and to assess variability among fish species and among
      sites according to watershed characteristics. The explicative variables
      correspond to muscular concentrations of pesticides (azoxystrobin, clomazone,
      diflufenican, carbendazim, isoproturon, metazachlor, napropamid) in three species
      of fish (Perca fluviatilis, Cyprinus carpio and Rutilus rutilus), caught in five
      ponds during two sampling campaigns. Management data are added variables in order
      to discuss about parameters suspected to be implicated in the contamination
      profiles recorded. RESULTS: This work shows that high amounts of pesticides
      applied, short crop rotation durations and bare soil practices led to
      contamination of sediments and fish and were associated to a "bad" management of
      watershed. Breeding fish that had low masses and establishing the fishing period
      at the end of winter seemed to be "bad" management of pond. Aggravating
      topological parameters were big watershed coupled to small pond and high
      proportions of sand soils in the watershed. CONCLUSIONS: Reducing amounts of
      pesticide used (e.g. policy agency plans, farmer acceptance), favouring long-term
      rotations and inter-cultures, adapting pond creation and fish farming practices
      to watershed management and topography all could reduce pesticide levels in
      edible fish and contribute to a better sustainability of the extensive fish
      farming in pond.

PMID- 22467232
TI  - Enhancement of natural radioactivity in fertilized soil of Faisalabad, Pakistan.
AB  - BACKGROUND, GOAL, AND SCOPE: Natural radioactivity in phosphate rock (PR) is
      transferred to phosphate fertilizer (PF) during the manufacturing process of the
      PF. The continuous addition of the PF to the cultivated soil accumulates the
      radionuclides in the land and increases the level of radioactivity in the soil.
      The purpose of the present study was to investigate the enhanced level of
      accumulated radioactivity due to the continuous addition of the PF in the
      farmlands of Nuclear Institute of Agriculture and Biology (NIAB) at Faisalabad in
      Pakistan. The selected study area consisted of the highly fertilized farmlands
      and an unfertilized barren land of the NIAB. INTRODUCTION: The understudy area is
      very fertile for the growth of various types of crops; therefore, four
      agricultural research institutes have been established at Faisalabad and NIAB is
      one of those. The NIAB has developed various research farmlands at different
      places in Pakistan. The crop yield has been increased by adding various
      fertilizers in the farmlands. The addition of the PF accompanied with the
      radionuclides enhances radioactivity in the fields. Human being is exposed
      directly or indirectly to this radiological hazard. A prolong exposure may become
      a cause of health risk. MATERIALS AND METHODS: The area of study consisted of
      three types of lands: the land under cultivation for the last 40 and 30 years
      called Site 1 and Site 2, respectively, and the barren land was called Site 3. A
      total of 75 soil samples were collected within the crop rooting zone (up to 25 cm
      deep) of the soil of the NIAB farms. The samples were dried, pulverized to
      powder, sealed in plastic containers, and stored to achieve equilibrium between
      (226)Ra and (222)Rn. Activity concentrations of the radionuclides (238)U
      ((226)Ra), (232)Th, and (40)K in soil samples were determined by using a high
      resolution gamma ray spectrometry system, consisting of an high purity germanium
      detector coupled through a spectroscopy amplifier with a PC based MCA installed
      with Geni-2000 software. RESULTS: The measured activity concentration levels of
      (40)K were 662 +/- 15, 615 +/- 17, and 458 +/- 20 Bq kg(-1), (226)Ra were 48 +/-
      6, 43 +/- 5, and 26 +/- 4 Bq kg(-1), and that of (232)Th were 39 +/- 5, 37 +/- 5,
      35 +/- 5 Bq kg(-1), respectively, in the soil of the Sites 1, 2, and 3. Gamma
      dose rate 1 m above the soil surface was 55, 51, and 40 nGy h(-1) from Sites 1,
      2, and 3, respectively. External dose rates in the rooms constructed of the
      bricks made of the soil from Sites 1, 2, and 3 were 161, 149, and 114 nGyh(-1),
      respectively. DISCUSSIONS: Activity concentration values of (40)K and (226)Ra in
      the soil of Sites 1 and 2 were higher than that in the soil of Site 3. The
      relative rise of (40)K was 43 % and 34 % and that of (226)Ra was 85 % and 65 %
      respectively in these sites. Activity concentrations of (232)Th in all these
      sites were in the background range. Gamma dose rate 1 m above soil surface of
      Sites 1 and 2 was 40 % and 30 % respectively higher than that from the soil of
      Site 3. The rise in activity of (40)K and (226)Ra and gamma dose from the Site 1
      was greater than that from the Site 2. The least activity and dose were observed
      from the Site 3. Gamma dose in the dwellings made of fertilized soil bricks of
      Site 1 and Site 2 were respectively calculated to be 41 % and 32 % higher than
      that in the abodes made of unfertilized soil bricks of Site 3. CONCLUSIONS:
      Activity concentrations of (226)Ra and (40)K were observed to be enhanced in the
      fertilized farmlands of the NIAB. Outdoor and indoor gamma dose as radiological
      hazard were found to be increasing with the continuous addition of PF in the
      understudy farmlands. RECOMMENDATIONS: It is recommended that naturally occurring
      radioactive metal should be removed during the process of manufacturing of the PF
      from the PR. PROSPECTIVE: The rise in radioactivity in the farmlands due to the
      addition of the PF can be a source of direct or indirect exposure to radiation
      that may enhance cancer risk of the exposed individuals.

PMID- 22467233
TI  - Origin and distribution of trace elements in high-elevation precipitation in
      southern China.
AB  - INTRODUCTION: During a 2009 investigation of the transport and deposition of
      trace elements in southern China, 37 event-based precipitation samples were
      collected at an observatory on Mount Heng, China (1,269 m asl). METHODS:
      Concentrations of trace elements were analyzed using inductively coupled plasma
      mass spectrometry and the wet deposition fluxes were established. A combination
      of techniques including enrichment factor analysis, principal component analysis,
      and back trajectory models were used to identify pollutant sources. RESULTS:
      Trace element concentrations at Mount Heng were among the highest with respect to
      measured values reported elsewhere. All elements were of non-marine origin. The
      elements Pb, As, Cu, Se, and Cd were anthropogenic, while Fe, Cr, V, Ba, Mn, and
      Ni were of mixed crustal/anthropogenic origin. The crustal and anthropogenic
      contributions of trace elements were 12.8 % (0.9 ~ 17.4 %) and 87.2 % (82.6 ~
      99.1 %), with the maximum crustal fraction being 17.4 % for Fe. Coal combustion,
      soil and road dust, metallurgical processes, and industrial activities
      contributed to the element composition. CONCLUSIONS: Summit precipitation events
      were primarily distant in origin. Medium- to long-range transport of trace
      elements from the Yangtze River Delta and northern China played an important role
      in wet deposition at Mount Heng, while air masses from south or southeast of the
      station were generally low in trace element concentrations.

PMID- 22467234
TI  - Synthesis and characterisation of Pd-modified N-doped TiO2 for photocatalytic
      degradation of natural organic matter (NOM) fractions.
AB  - INTRODUCTION: The removal of natural organic matter (NOM) from water is becoming
      increasingly important in order to prevent the formation of carcinogenic
      disinfection by-products. The inadequate removal of NOM has a bearing on the
      capacity of the other treatment processes to remove organic micro-pollutants or
      inorganic species that may be present in the water. New methods are therefore
      currently being sought to effectively characterise NOM and also to ensure that it
      is sufficiently removed from drinking water sources. METHODOLOGY: Nitrogen- and
      palladium-co-doped TiO(2) was synthesised by a modified sol-gel method and
      evaluated for its photocatalytic degradation activity on NOM fractions under
      simulated solar radiation. The photocatalyst was characterised by FT-IR, Raman,
      XRD, DRUV-vis, SEM, TEM, EDS, XPS and TGA. FT-IR confirmed the presence of OH
      groups on thermally stable, nearly spherical anatase nanoparticles with an
      average diameter of 20 nm. PdO species appeared on the surface of the TiO(2) as
      small uniformly dispersed particles (2 to 3 nm). A red shift in the absorption
      edge compared to commercial anatase TiO(2) was confirmed by DRUV-vis. In order to
      gain a better insight into the response of NOM to photodegradation, the NOM was
      divided into three different fractions based on its chemical nature. RESULTS AND
      DISCUSSION: Photodegradation efficiencies of 96, 38 and 15 % were realised for
      the hydrophobic, hydrophilic and transphilic NOM fractions, respectively. A
      reasonable mechanism was proposed to explain the photocatalytic degradation of
      the NOM fractions. The high photocatalytic activity could be attributed to the
      larger surface area, smaller crystalline size and synergistic effects of the co
      dopants N and Pd in the TiO(2) crystal.

PMID- 22467235
TI  - Evaluation of the individuality of white rot macro fungus for the decolorization
      of synthetic dye.
AB  - INTRODUCTION: A biosorbent was developed by simple dried Agaricus bisporus (SDAB)
      and effectively used for the biosorption of cationic dyes, Crystal Violet and
      Brilliant Green. MATERIALS AND METHODS: For the evaluation of the biosorbent
      system, all the batch equilibrium parameters like pH, biomass dose, contact time,
      and temperature were optimized to determine the decolorization efficiency of the
      biosorbent. The maximum yields of dye removal were achieved at pH 4.0 for Crystal
      Violet (CV) and pH 5.0 for Brilliant Green (BG), which are closer to their
      natural pH also. RESULT AND DISCUSSION: Equilibrium was established at 60 and 40
      min for CV and BG, respectively. Pseudo first-order, pseudo second-order, and
      intraparticle-diffusion kinetic models were studied at different temperatures.
      Isotherm models such as Freundlich, Langmuir, and Dubinin-Radushkevich were also
      studied. Biosorption processes were successfully described by Langmuir isotherm
      model and the pseudo second-order kinetic model. CONCLUSIONS: The biosorption
      capacity of A. bisporus over CV and BG were found as 21.74 and 12.16 mg gm(-1).
      Thermodynamic parameters indicated that the CV and BG dye adsorption onto A.
      bisporus is spontaneous and exothermic in the single and ternary systems.
      Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared
      spectroscopy were used for the surface morphology, crystalline structure of
      biosorbent, and dye-biosorbent interaction, respectively. This analysis of the
      biosorption data confirmed that these biosorption processes are ecofriendly and
      economical. Thus, this biomass system may be useful for the removal of
      contaminating cationic dyes.

PMID- 22467236
TI  - Report on the Second Annual Conference of COST Action FA0905, "what's for lunch?
      Nutrients and minerals in every day food. How the knowledge on mineral nutrition
      of plants can improve human nutrition". Venice, Italy, 24-25 November 2011.

PMID- 22467237
TI  - Thermophilic desulfurization of dibenzothiophene and different petroleum oils by
      Klebsiella sp. 13T.
AB  - PURPOSE: Biodesulfurization (BDS) has the potential to desulfurize
      dibenzothiophene (DBT) and its alkylated derivatives, the compounds that are
      otherwise refractory to hydrodesulfurization (HDS). Thermophilic microorganisms
      are more appropriate to be used for BDS applications following HDS. The aim of
      the present study was to isolate a thermophilic microorganism and to explore its
      commercial relevance for BDS process. METHODS: The desulfurizing thermophilic
      strain was isolated and enriched from various soil and water samples using sulfur
      free medium (SFM) supplemented with DBT. Microbiological and genomic approach was
      used to characterize the strain. Desulfurization reactions were carried out using
      DBT and petroleum oils at 45 degrees C followed by different analytical
      procedures. RESULTS: We report the isolation of a thermophilic bacterium
      Klebsiella sp. 13T from contaminated soils collected from petroleum refinery.
      HPLC analysis revealed that Klebsiella sp. 13T could desulfurize DBT to 2
      hydroxybiphenyl (2-HBP) at 45 degrees C through 4S pathway. In addition, adapted
      cells of Klebsiella sp. 13T were found to remove 22-53% of sulfur from different
      petroleum oils with highest sulfur removal from light crude oil. CONCLUSION:
      Klebsiella sp. 13T is a potential candidate for BDS because of its thermophilic
      nature and capability to desulfurize petroleum oils.

PMID- 22467238
TI  - HIF1alpha regulated expression of XPA contributes to cisplatin resistance in lung
      cancer.
AB  - Factors regulating nucleotide excision repair probably contribute to the
      heterogenous response of advanced stage lung cancer patients to drugs such as
      cisplatin. Studies to identify the genes in the nucleotide excision repair
      pathway most closely associated with resistance to cisplatin have not been
      conclusive. We hypothesized that Xeroderma pigmentosum complementation group A
      (XPA), because of its dual role in sensing and recruiting other DNA repair
      proteins to the damaged template, would be critical in defining sensitivity to
      cisplatin. Studies were conducted to identify factors regulating transcription of
      XPA, to assess its role in modulating sensitivity to cisplatin and its expression
      in primary lung tumors. Hypoxia-inducible factor 1 alpha (HIF1alpha) subunit was
      found to bind with strong affinity to a hypoxia response element sequence in the
      promoter of XPA. Modulating expression of HIF1alpha by small interfering RNA or
      cobalt chloride markedly reduced or increased transcription of XPA in lung cancer
      cell lines, respectively. Protein levels of XPA were strongly correlated with
      sensitivity to cisplatin (r = 0.88; P < 0.001) in cell lines and sensitivity
      could be increased by small interfering RNA depletion of XPA. Expression of XPA
      determined in 54 primary lung tumors was elevated on average 5.2-fold when
      compared with normal bronchial epithelial cells and correlated with levels of
      HIF1alpha (r = 0.58; P < 0.01). Together, these studies identify XPA as a novel
      target for regulation by HIF1alpha whose modulation could impact lung cancer
      therapy.

PMID- 22467240
TI  - Ordered nanopillar structured electrodes for depleted bulk heterojunction
      colloidal quantum dot solar cells.
AB  - A bulk heterojunction of ordered titania nanopillars and PbS colloidal quantum
      dots is developed. By using a pre-patterned template, an ordered titania
      nanopillar matrix with nearest neighbours 275 nm apart and height of 300 nm is
      fabricated and subsequently filled in with PbS colloidal quantum dots to form an
      ordered depleted bulk heterojunction exhibiting power conversion efficiency of
      5.6%.

PMID- 22467239
TI  - Knockdown of AGR2 induces cellular senescence in prostate cancer cells.
AB  - Anterior-gradient 2 (AGR2), overexpressed in many tumors including prostate
      cancer (PCa), is implicated in stimulation of cell proliferation, adhesion, anti
      apoptosis and cell cycle regulation. Here, a potential role of AGR2 in cellular
      senescence was investigated. We first observed that AGR2 was overexpressed in
      Chinese Han PCa tissues and had a positive correlation with cyclin D1 and p-Rb
      but not with p16(INK4a). AGR2 expression profiles varied among cell lines, with
      PC3 cells being the highest level, LNCaP and DU145 relatively less. The
      expression of cyclin D1 showed similar pattern to the AGR2 in cell lines.
      Knockdown of AGR2 caused a decrease in cell viability in PC3 cells, whereas
      forced expression of AGR2 led to an increased cell proliferation of LNCaP and
      DU145 cells. Importantly, AGR2 depletion resulted in accumulation of cells at the
      G(0)/G(1) phase and induction of cellular senescence in all three PCa cell lines
      as indicated by an increase of flat, enlarged and senescence-associated beta
      galactosidase (SA-beta-Gal) positive cells. Senescent response to AGR2 silencing
      was also evidenced by elevated gammaH2AX and fluorescent punctuate formation of
      tri-methyl-histone H3 in AGR2-depleted cells. Further studies indicated that
      LNCaP underwent a p21(CIP1)-dependent cellular senescence in response to AGR2
      depletion that requires inactivation of ERK signaling, whereas PC-3 was also
      p21(CIP1) dependent but involved in suppression of PI3K/Akt. Unlike LNCaP and PC
      3, senescent response of DU145 was found to be mainly p27(KIP1) dependent that
      may require upregulation of PTEN and inhibition of PI3K/Akt signaling. Thus,
      these findings suggest a novel role of AGR2 in regulation of cellular senescence.

PMID- 22467241
TI  - V-ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differentiation,
      extracellular acidification, lysosomal trafficking, and protease exocytosis in
      osteoclast-mediated bone resorption.
AB  - Lysosomal trafficking and protease exocytosis in osteoclasts are essential for
      ruffled border formation and bone resorption. Yet the mechanism underlying
      lysosomal trafficking and the related process of exocytosis remains largely
      unknown. We found ATP6ap1 (Ac45), an accessory subunit of vacuolar-type H(+)
      ATPases (V-ATPases), to be highly induced by receptor activator for nuclear
      factor kappa B ligand (RANKL) in osteoclast differentiation. Ac45 knockdown
      osteoclasts formed normal actin rings, but had severely impaired extracellular
      acidification and bone resorption. Ac45 knockdown significantly reduced
      osteoclast formation. The decrease in the number of osteoclasts does not result
      from abnormal apoptosis; rather, it results from decreased osteoclast precursor
      cell proliferation and fusion, which may be partially due to the downregulation
      of extracellular signal-regulated kinase (ERK) phosphorylation and FBJ
      osteosarcoma oncogene (c-fos), nuclear factor of activated T-cells, cytoplasmic 1
      (NFATc1), and "transmembrane 7 superfamily member 4" (Tm7sf4) expression.
      Notably, Ac45 knockdown osteoclasts exhibited impaired lysosomal trafficking and
      exocytosis, as indicated by the absence of lysosomal trafficking to the ruffled
      border and a lack of cathepsin K exocytosis into the resorption lacuna. Our data
      revealed that the impaired exocytosis is specifically due to Ac45 deficiency, and
      not the general consequence of a defective V-ATPase. Together, our results
      demonstrate the essential role of Ac45 in osteoclast-mediated extracellular
      acidification and protease exocytosis, as well as the ability of Ac45 to guide
      lysosomal intracellular trafficking to the ruffled border, potentially through
      its interaction with the small guanosine-5'-triphosphatase (GTPase) Rab7. Our
      work indicates that Ac45 may be a novel therapeutic target for osteolytic
      disease.

PMID- 22467242
TI  - Dietary beliefs and behavior among inflammatory bowel disease patients.
AB  - BACKGROUND: We investigated dietary beliefs and behavior in a large population of
      adult inflammatory bowel disease (IBD) patients and evaluated their impact on
      patients' social life. METHODS: A questionnaire of 14 items was administered to
      all consecutive IBD patients followed at the Nancy University Hospital Department
      of Gastroenterology from February to July 2011. RESULTS: A total of 244 patients
      participated in the survey; 15.6% (n = 38) of patients believed that diet could
      initiate the disease, while 57.8% (n = 141) believed that food can play a role in
      causing a relapse. Forty percent (107/244) of patients identified food as a risk
      factor for relapse. Seventy-three percent of respondents reported having already
      received nutritional advice. The majority of respondents (47.5%, n = 116)
      reported that the disease had changed the pleasure of eating. Only one-quarter of
      patients had a normal diet in case of relapse. Almost two out of three patients
      (66.8%, n = 163) reported not eating certain foods they usually like to eat in
      order to prevent a relapse. Dietary beliefs and behavior had an impact on their
      social life for one-fifth of patients. Excluding food was associated with
      refusing outdoor dining for fear of causing relapse (P = 0.006) and not sharing
      the same menu as the other members of the family living under the same roof (P =
      0.002). CONCLUSIONS: The majority of IBD patients are avoiding certain foods.
      Dietary beliefs and behavior have a strong impact on their social life.

PMID- 22467243
TI  - Prognostic value of Ki-67 labeling index in patients with node-negative, triple
      negative breast cancer.
AB  - The aim of this analysis was to investigate the usefulness of Ki-67 labeling
      index (LI) for the identification of different prognostic subgroups in primary
      node-negative, triple negative breast cancer (TNBC) patients. From January 1997
      to December 2005, 1,053 patients operated for TNBC were identified through the
      institutional clinical database. The study was performed in accordance with
      REMARK criteria. The relationship between Ki-67LI and the risk of breast-related
      deaths was evaluated with a multivariable Cox regression model. Cubic splines
      were used to model Ki-67LI as a continuous variable. We selected 496 consecutive
      patients with node-negative TNBC. Median age was 52 years, median Ki-67LI 48%
      (range 4-95), and median follow up 6 years (range 0.5-13). Total deaths and
      deaths from BC were 52 (10.5%) and 38 (7.7%), respectively. Ki-67LI increased
      with decreasing age (P<0.01), increasing tumor size (P<0.01), and grade (P<0.01).
      When analyzing Ki-67LI as a continuous variable, the risk of death from BC
      increased steeply with increasing Ki-67LI up to about 35% and remained flat for
      higher values (adjusted effect of Ki-67 P=0.049; adjusted nonlinear effect
      P=0.021). Accordingly, when dividing patients into lower (<=35%) and higher
      (>35%) Ki-67LI subgroups, the 5-year cumulative incidence of breast-related
      deaths were 2.3 and 9.0%, respectively, with an adjusted HR(>35 vs <=35) of 2.3
      (95% CI 1.0-5.8, P=0.046). Within the group of patients with node-negative TNBC,
      Ki-67LI was associated with different prognoses subgroups. Ki-67LI might be
      useful in the design of trials of risk-adapted adjuvant therapies.

PMID- 22467244
TI  - Mechanism of tissue-specific farnesoid X receptor in suppressing the expression
      of genes in bile-acid synthesis in mice.
AB  - Activation of farnesoid X receptor (Fxr, Nr1h4) is a major mechanism in
      suppressing bile-acid synthesis by reducing the expression levels of genes
      encoding key bile-acid synthetic enzymes (e.g., cytochrome P450 [CYP]7A1/Cyp7a1
      and CYP8B1/Cyp8b1). FXR-mediated induction of hepatic small heterodimer partner
      (SHP/Shp, Nr0b2) and intestinal fibroblast growth factor 15 (Fgf15; FGF19 in
      humans) has been shown to be responsible for this suppression. However, the exact
      contribution of Shp/Fgf15 to this suppression, and the associated cell-signaling
      pathway, is unclear. By using novel genetically modified mice, the current study
      showed that the intestinal Fxr/Fgf15 pathway was critical for suppressing both
      Cyp7a1 and Cyp8b1 gene expression, but the liver Fxr/Shp pathway was important
      for suppressing Cyp8b1 gene expression and had a minor role in suppressing Cyp7a1
      gene expression. Furthermore, in vivo administration of Fgf15 protein to mice led
      to a strong activation of extracellular signal-related kinase (ERK) and, to a
      smaller degree, Jun N-terminal kinase (JNK) in the liver. In addition, deficiency
      of either the ERK or JNK pathway in mouse livers reduced the basal, but not the
      Fgf15-mediated, suppression of Cyp7a1 and Cyp8b1 gene expression. However,
      deficiency of both ERK and JNK pathways prevented Fgf15-mediated suppression of
      Cyp7a1 and Cyp8b1 gene expression. CONCLUSION: The current study clearly
      elucidates the underlying molecular mechanism of hepatic versus intestinal Fxr in
      regulating the expression of genes critical for bile-acid synthesis and
      hydrophobicity in the liver.

PMID- 22467245
TI  - Targeting cytokine signaling as an innovative therapeutic approach for the
      prevention of atherosclerotic plaque development.

PMID- 22467246
TI  - Smoking increases recurrent viral hepatitis after liver transplantation.
AB  - Smoking is a common behavior among transplant candidates. The aim of this study
      was to evaluate the effects of smoking on a range of complications after liver
      transplantation. We reviewed data about patient demographics and various
      complications after liver transplantation that were recorded in the McGill
      University Health Centre liver transplant database over a 14-year period. chi(2)
      and multivariate analyses were performed. Four hundred forty-four liver
      transplants were performed from 1990 to 2004, and 63 were repeat transplants.
      Only primary liver transplant recipients were included in our analysis. Smokers
      (ie, active or former smokers) were more likely to be male (77.9% versus 62.7%, P
      = 0.009) and Caucasian (88.4% versus 78.0%, P = 0.03). The median survival time
      was 13.23 years for smokers and was not estimable for nonsmokers because of
      censoring. The median recurrent viral hepatitis-free survival time was 0.87 years
      for smokers and 4.10 years for nonsmokers (P = 0.03). The following variables
      were not found to be associated with the smoking status: patient survival (P =
      0.78), time to biliary complications after liver transplantation (P = 0.67), time
      to the first rejection episode after liver transplantation (P = 0.61), and time
      to depression after liver transplantation (P = 0.67). A Cox proportional hazards
      regression showed that recurrent viral hepatitis-free survival was still strongly
      associated with smoking [HR = 2.04, 95% confidence interval (CI) = 1.13-3.68, P =
      0.018] and was marginally associated with East Asian race (HR = 0.26, 95% CI =
      0.06-1.06, P = 0.06) and male sex (HR = 0.59, 95% CI = 0.34-1.02, P = 0.06). In
      conclusion, recurrent viral hepatitis-free survival was decreased for smokers
      after liver transplantation, likely because of the adverse effects of tobacco on
      immunological host defenses. Overall, the biliary complication-free, depression
      free, and rejection-free survival rates were similar for smokers and nonsmokers.
      These findings suggest that smoking cessation should be encouraged, particularly
      in recipients undergoing transplantation for viral hepatitis.

PMID- 22467247
TI  - Is there any difference in human pupillary reaction to acupuncture between light-
      and dark-adaptive conditions?
AB  - OBJECTIVES: To determine if acupuncture stimulation elicits a pupillary response
      under light adaptation and whether there is any difference in the pupillary
      response between light and dark adaptation environments during acupuncture
      stimulation. METHODS: The participants consisted of 55 healthy individuals who
      had no known eye diseases or pupil abnormalities. Experiment 1 compared pupillary
      responses between acupuncture stimulation and no-stimulation groups under light
      adaptation. Experiment 2 compared pupillary responses to acupuncture between two
      conditions (dark and light adaptation) with a two-period repeated measurement
      crossover design. For both experiments the pupil diameter was continuously
      measured for 3 min before stimulation, during stimulation and for 3 min after
      stimulation. For all acupuncture stimulation interventions an acupuncture needle
      was inserted superficially at the TE5 acupuncture point followed by gentle
      tapping stimulation for 90 s. RESULTS: In experiment 1 the pupil diameter was
      significantly decreased during (p<0.01) and after stimulation (p<0.0001) compared
      with the pupil diameter before stimulation under light adaptation. No significant
      difference was noted in the serial changes in pupil diameter in the no
      stimulation group. In experiment 2 the pupil diameter was significantly decreased
      90 s after stimulation (p<0.05) and 150 s after stimulation (p<0.05) under light
      adaptation conditions. Furthermore, the pupil diameter was significantly
      decreased 120 s after stimulation (p<0.05) and 150 s after stimulation (p<0.01)
      under dark adaptation conditions. No significant difference in the serial changes
      in pupil diameter was noted between the groups. CONCLUSIONS: This study shows
      that pupil constriction occurs following acupuncture stimulation under light
      adaptation and this response is no different from that seen under dark
      adaptation.

PMID- 22467248
TI  - Characterisation of human skin impedance at acupuncture point PC4 Ximen and
      pericardium meridian using the four-electrode method.
AB  - INTRODUCTION: Traditional Chinese medicine offers several theories to explain the
      mechanism of acupuncture. One of these theories proposes that acupuncture points
      and meridians have unique electrical properties and their electrical skin
      impedance is lower than surrounding areas. The aim of this study was to evaluate
      the differences in electrical skin impedance between PC4 and the pericardium
      meridian compared with the surrounding areas. METHODS: Eighteen healthy subjects
      (10 women) were recruited to participate in the study. An impedance meter based
      on the four-electrode technique was designed specifically for the study. Twenty
      five points were marked on the skin: one on the point PC4, four others on the
      pericardium meridian and 20 points around it. The electrical impedance of each
      point was measured with the four-electrode device. RESULTS: The mean electrical
      skin impedance at PC4 was significantly different from the 20 of the surrounding
      points but not significantly different from the four adjacent points. The mean
      skin impedance of the five points over the pericardium meridian was significantly
      different from that of parallel rows of points using repeated measures analysis
      of variance (p<0.001) CONCLUSION: Within the possible limits of this measurement
      technique, skin impedance along the pericardium meridian is lower than
      surrounding areas, supporting the idea of different properties of the pericardium
      meridian compared with the control areas. Evidence on skin impedance at PC4 is
      inconclusive and further studies are needed.

PMID- 22467249
TI  - Molecular investigation of Ewing sarcoma: about detecting translocations.

PMID- 22467250
TI  - Technology of streptomycin sulfate separation by two-stage foam separation.
AB  - Industrial discharges from manufacturing streptomycin sulfate (SS) are inhibitory
      to biological wastewater treatment and need to be stripped of residual SS. For
      effective SS recovery from the wastewater, a two-stage foam separation technology
      was investigated using a column with a vertical ellipsoid-shaped channel (VEC)
      and a conventional one, and sodium dodecyl sulfate (SDS) served as the collector.
      The mechanism of enhancing foam drainage by VEC was theoretically analyzed. In
      the first stage, the column with VEC was used and under the optimal conditions of
      the liquid-loading volume 300 mL, volumetric airflow rate 100 mL/min, the initial
      pH 7.0 and the molar ratio of SDS to SS 8.0, an improved SS enrichment ratio of
      16.7 was obtained. In the second stage, a conventional column was used and with a
      volumetric airflow rate of 450 mL/min, the foamate had a SS concentration of
      about 0.5 g/L, so it was used as the feed solution of the first stage. By the two
      stage technology, the total SS recovery percentage reached as high as 99.7%.
      Thus, it was significantly effective for the two-stage foam separation technology
      to recover SS from the simulative wastewater.

PMID- 22467251
TI  - Hippocampal polyamine levels and transglutaminase activity are paralleling
      spatial memory retrieval in the C57BL/6J mouse.
AB  - Although a potential role for polyamines and transglutaminases (TGs) in memory
      mechanisms have been proposed, hippocampal spermine (SPM) and spermidine (SPD)
      levels as well as transamidating activity of TG in spatial memory have not been
      addressed yet. It was therefore the aim of the study to assess hippocampal
      polyamines and TG activity at the probe trial in a spatial memory paradigm.
      C57BL/6J mice (20 animals per group) were used for the experiments and divided
      into a trained and a yoked (untrained) group. The Morris water maze (MWM) was
      selected as the memory test, animals were sacrificed within 5 min following the
      probe trial and hippocampi were taken for biochemical analysis. SPD and SPM
      levels were assessed by an analytical procedure according to Gismondi et al.
      Transamidating activity of TG was determined following the method described by
      Chung and Folk using [14C] methylamine as substrate. gamma-(Glutamyl)-polyamine
      levels were evaluated by ion exchange chromatography according to Folk et al.
      Animals learned the task in the MWM as latencies and pathlengths were
      significantly reduced. At the probe trial mice showed significantly higher
      preference for the target quadrant. Free SPD and SPM levels were manifold
      decreased in the trained as compared to the yoked group. Transamidating activity
      of TG was fourfold increased in trained as compared to yoked controls. gamma
      (Glutamyl)-SPD was comparable while gamma-(glutamyl)-SPM was significantly higher
      in the trained group. The findings show a potential role for polyamines, their
      derivative gamma-(glutamyl)-SPM and transamidating activity of TG at memory
      retrieval or formation. Results from this study are extending and knowledge on
      polyamines and report for the first time involvement of gamma-(glutamyl)-SPM and
      transamidating activity of TG that may form the basis for future neurochemical
      and pharmacological studies and indeed, modulation of polyamine and TG activity
      has been already proposed as a tentative therapeutical concept.

PMID- 22467252
TI  - Analysis of drugs for the therapy of anticholinesterase poisoning.

PMID- 22467253
TI  - Development and validation of a UPLC-ESI-MS/MS method for the determination of N
      butylscopolamine in human plasma: application to a bioequivalence study.
AB  - A sensitive and fast ultra performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method for measurements of N
      butylscopolamine in plasma was developed and validated. A single protein
      precipitation was proposed for the clean up of the plasma and N-methylhomatropine
      was added as internal standard (IS). The analyses were carried out using a C(18)
      column and mobile phase of acetonitrile: 5 mM ammonium acetate + 0.1% formic acid
      (90:10, v/v). The triple quadrupole mass spectrometer equipped with an
      electrospray source in positive mode, was set up in selective reaction
      monitoring, to detect precursor -> product ion 360.0 -> 194.0 m/z and 290.3 ->
      138.0 m/z transitions, for N-butylscopolamine and IS, respectively. The method
      was linear in 0.03 (lower limit of quantitation; LLOQ) - 10.00 ng/ml range for N
      butylscopolamine. Satisfactory selectivity, linearity, precision, accuracy, and
      robustness were obtained for the UPLC-ESI-MS/MS method. The proposed method was
      successfully applied to a pharmacokinetic study of healthy human volunteers; the
      results showed that the two scopolamine butylbromide formulations tested are not
      bioequivalent in rate and extent of absorption.

PMID- 22467254
TI  - Rapid resolution liquid chromatography for monitoring the quality of stockpiled
      atropine preparations for injection.
AB  - We describe a rapid resolution liquid chromatography (RRLC) method for analyzing
      atropine sulfate, its degradation products (tropic acid, apoatropine, atropic
      acid) and other components (e.g. phenol, methylparaben) in injectable medicines
      that are used by the German armed forces in emergency situations. Chromatography
      is performed using an acetonitrile/phosphate buffer gradient (pH = 1.0) and an RP
      18 column (50 x 4.6 mm, 1.8 um) with the detection wavelength set at 220 nm. The
      concentration of the active ingredient (atropine sulfate) in the tested products
      ranges from about 1 mg*ml(-1) to 10 mg*ml(-1) . The concentrations of the
      detected degradation products range from 0.2% to 4.7% (tropic acid) in relation
      to the active pharmaceutical ingredient (API). Using shorter separation columns
      and smaller particle sizes of the stationary phase improved analysis time from 40
      to 10 min and reduced the consumption of solvents by approximately 75%. Owing to
      the pressure conditions (< 200 bar), UHPLC (ultra high performance liquid
      chromatography) systems are not needed. Comparison of the atropine and tropic
      acid results obtained with the previously used HPLC (high performance liquid
      chromatography) method of the MAH (marketing authorization holder) show that
      there is no indication of a significant difference between the two methods.

PMID- 22467255
TI  - A pro-apoptotic 15-kDa protein from Bacopa monnieri activates caspase-3 and
      downregulates Bcl-2 gene expression in mouse mammary carcinoma cells.
AB  - In diseases such as cancer, induction of apoptosis has been a new target for
      mechanism-based drug discovery. The central component of the process of apoptosis
      is a proteolytic system involving a family of proteases called caspases.
      Apoptosis involves characteristic morphological and biochemical events ultimately
      leading to cell demise. Apoptotic induction is evidently central to the mechanism
      of action of plant-derived anticancer drugs. Extract of the medicinal plant,
      Bacopa monnieri, inhibits tumor cell proliferation and accumulation of malignant
      ascites fluid. The crude sample when subjected to Soxhlet extraction yielded
      different solvent extracts of which the aqueous extract showed biological
      activity of apoptosis in Ehrlich ascites tumor cell lines (EAT). Bacopa monnieri
      water extract (BMWE) treatment of EAT cells produced apoptotic morphological
      characteristics and in-vivo DNA fragmentation, which is due to the activity of an
      endogenous endonuclease. The endonuclease responsible for DNA fragmentation acts
      downstream of caspase-3 activity and is also referred to as caspase-activated
      DNase (CAD). The CAD constitutively expressed in the cell cytoplasm is
      translocated into the nucleus upon BMWE treatment, as verified by Western
      blotting, leading to DNA fragmentation and to programmed cell death. The
      expression of the pro-apoptotic gene Bax was increased and the expression of the
      anti-apoptotic gene Bcl-2 was decreased by BMWE treatment. Considering the above
      results, BMWE was able induce apoptosis in EAT cells via Bax-related caspase-3
      activation. This may provide experimental data for the further clinical use of
      BMWE in cancer.

PMID- 22467256
TI  - Three-dimensional biomimetic patterning in hydrogels to guide cellular
      organization.
AB  - An image-guided micropatterning method is demonstrated for generating biomimetic
      hydrogel scaffolds with two-photon laser scanning photolithography. This process
      utilizes computational methods to directly translate three-dimensional
      cytoarchitectural features from labeled tissues into material structures. We use
      this method to pattern hydrogels that guide cellular organization by structurally
      and biochemically recapitulating complex vascular niche microenvironments with
      high pattern fidelity at the microscale.

PMID- 22467257
TI  - Evaluation of bioartificial renal tubule device prepared with lifespan-extended
      human renal proximal tubular epithelial cells.
AB  - BACKGROUND: Acute kidney injury (AKI), accompanied by the development of systemic
      inflammatory response syndrome and multiorgan dysfunction syndrome, is associated
      with a high risk of death. Bioartificial renal tubule device (BTD) is a cell
      therapy that improves the conditions common to artificial kidney recipients
      treated for kidney diseases. In this paper, we describe the establishment of BTD
      with lifespan-extended human renal proximal tubular epithelial cells. METHODS:
      AKI goats were established by performing bilateral nephrectomy followed by
      lipopolysaccharide administration. The AKI goats were treated with BTD or sham
      BTD, and the two groups of animals were compared by measuring the respective life
      spans and the levels of blood urea nitrogen, creatinine, alanine
      aminotransferase, aspartate aminotransferase, lactate dehydrogenase and serum
      electrolytes. The expression levels of inflammatory cytokines were detected by
      reverse transcription-polymerase chain reaction, and plasma interleukin (IL)-6
      levels were measured by enzyme-linked immunosorbent assay. RESULTS: The life span
      of AKI goats was extended: the lifetime with the BTD treatment compared with sham
      BTD. BTD and sham-BTD showed a similar degree of small solute clearance. The
      expression levels of inflammatory cytokines and plasma IL-6 levels were decreased
      by the BTD treatment. CONCLUSIONS: BTD treatment results in less damage from
      endotoxin shock and increased life span in AKI goats. These results suggest that
      BTD may be a useful component of bioartificial kidneys and should be considered
      in the next generation of renal replacement therapies.

PMID- 22467258
TI  - Trisodium citrate induced protein precipitation in haemodialysis catheters might
      cause pulmonary embolism.
AB  - BACKGROUND: The locking anticoagulant plays a decisive role in the patency of
      central venous catheters (CVCs) used for haemodialysis. During injection, the
      hydraulic effects inevitably cause lock solution to spill into the systemic
      circulation. Density differences between whole blood (WB) and the lock solution
      cause further gravity-induced seepage of lock solution. This is followed by an
      influx of WB into the catheter, also described for trisodium citrate, which is a
      common agent for serum protein precipitation. Embolic complications from
      haemodialysis catheters locked with hypertonic trisodium citrate have been
      reported. We aimed to investigate protein precipitation in trisodium citrate
      locked catheters as a possible cause of pulmonary embolisms. METHODS: In vitro,
      WB and trisodium citrate (concentrations ranging from 4.7 to 46.7%) mixtures in a
      ratio of 1:4 were used to assess protein precipitation. Additionally,
      WB/trisodium citrate mixture was pumped through a 20-MUm mesh filter, simulating
      pulmonary vessels, and filtrate pressure was measured. In vivo, listed filling
      volumes of haemodialysis catheters locked with trisodium citrate 4% (n=10), 10%
      (n=10), 20% (n=10) or 46.7% (n=10) were aspirated and then analysed for protein
      precipitation. RESULTS: In vitro, protein precipitation capable of causing filter
      occlusion was observed in test solutions containing trisodium citrate above a
      concentration of 12%. In vivo, protein precipitation was detected in all samples
      from the CVCs filled with trisodium citrate 46.7% (n=10) and 20% (n=10). In
      contrast, there were no signs of precipitation in samples from the catheters
      filled with trisodium citrate 4% (n=10) or 10% (n=10). CONCLUSIONS: Our in vitro
      results demonstrate that protein precipitates inside haemodialysis catheters when
      trisodium citrate is used above the concentrations of 12%. Precipitated protein
      may have contributed to the pathophysiology of reported embolisms from
      haemodialysis catheters filled with hypertonic trisodium citrate. Based on our
      findings, we suggest that trisodium citrate lock solution up to the concentration
      of 10% can be used safely.

PMID- 22467259
TI  - Higher dietary fructose is associated with impaired hepatic adenosine
      triphosphate homeostasis in obese individuals with type 2 diabetes.
AB  - Fructose consumption predicts increased hepatic fibrosis in those with
      nonalcoholic fatty liver disease (NAFLD). Because of its ability to lower hepatic
      adenosine triphosphate (ATP) levels, habitual fructose consumption could result
      in more hepatic ATP depletion and impaired ATP recovery. The degree of ATP
      depletion after an intravenous (IV) fructose challenge test in low- versus high
      fructose consumers was assessed. We evaluated diabetic adults enrolled in the
      Action for Health in Diabetes Fatty Liver Ancillary Study (n = 244) for whom
      dietary fructose consumption estimated by a 130-item food frequency questionnaire
      and hepatic ATP measured by phosphorus magnetic resonance spectroscopy and uric
      acid (UA) levels were performed (n = 105). In a subset of participants (n = 25),
      an IV fructose challenge was utilized to assess change in hepatic ATP content.
      The relationships between dietary fructose, UA, and hepatic ATP depletion at
      baseline and after IV fructose challenge were evaluated in low- (<15 g/day)
      versus high-fructose (>= 15 g/day) consumers. High dietary fructose consumers had
      slightly lower baseline hepatic ATP levels and a greater absolute change in
      hepatic alpha-ATP/ inorganic phosphate (Pi) ratio (0.08 versus 0.03; P = 0.05)
      and gamma-ATP /Pi ratio after an IV fructose challenge (0.03 versus 0.06; P =
      0.06). Patients with high UA (>= 5.5 mg/dL) showed a lower minimum liver ATP/Pi
      ratio postfructose challenge (4.5 versus 7.0; P = 0.04). CONCLUSIONS: High
      fructose consumption depletes hepatic ATP and impairs recovery from ATP depletion
      after an IV fructose challenge. Subjects with high UA show a greater nadir in
      hepatic ATP in response to fructose. Both high dietary fructose intake and
      elevated UA level may predict more severe hepatic ATP depletion in response to
      fructose and hence may be risk factors for the development and progression of
      NAFLD.

PMID- 22467260
TI  - Role of antithrombotic agents in heart failure.
AB  - Despite a vast body of research on antithrombotic therapy for patients with
      cardiac disease, there are few clinical settings where robust evidence of their
      benefit exists. Patients with heart failure often have vascular disease and
      atrial fibrillation contributing to their poor prognosis. For patients with heart
      failure and atrial fibrillation, anticoagulants are appropriate. For patients
      with heart failure in sinus rhythm, the weight of evidence suggests that doctors
      should generally avoid using any antithrombotic agent even if the patient has
      coronary artery disease. If there is a compulsion to treat, then there is less
      evidence of harm with clopidogrel or warfarin than with aspirin, although most
      receive aspirin. More research is required for this "evidence-light" problem. For
      those with the opportunity, engaging with a randomized trial is clinically and
      scientifically appropriate. The dilemma for such studies is the comparator.
      Should it be against or in addition to "standard of care" or both?

PMID- 22467262
TI  - Associations between vitamin D receptor polymorphisms and susceptibility to
      ulcerative colitis and Crohn's disease: a meta-analysis.
AB  - BACKGROUND: Several polymorphisms have been identified in the vitamin D receptor
      (VDR) gene, while their roles in the incidence of ulcerative colitis (UC) and
      Crohn's disease (CD) are conflicting. This meta-analysis was designed to clarify
      the impact of these polymorphisms on UC and CD risk. METHODS: The PubMed, Embase,
      and Cochrane electronic databases were searched from February 1995 to August 2011
      for studies on the four VDR polymorphisms: TaqI, BsmI, FokI, and ApaI. Data were
      extracted and pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were
      calculated. RESULTS: Nine studies were included. In Asians, the ff genotype of
      FokI was associated with increased UC risk (OR = 1.65; 95% CI, 1.11- 2.45). The
      "a" allele carrier status of ApaI appeared to be a protective factor for CD (OR =
      0.81; 95% CI, 0.67-0.97). The tt genotype increased the risk of CD in Europeans
      (OR = 1.23; 95% CI, 1.02-1.49). Moreover, the tt genotype of TaqI in males had a
      moderate elevated risk of UC (OR = 1.56; 95% CI, 1.02-2.39) and CD (OR = 1.84;
      95% CI, 1.19-2.83). CONCLUSIONS: The meta-analysis reveals a significant increase
      in CD risk for Europeans carrying TaqI tt genotype and a significant decrease in
      CD risk for all carriers of the Apal "a" allele. For Asians, the VDR FokI
      polymorphism appears to confer susceptibility to UC. For males, the TaqI tt
      genotype is associated with susceptibilities to both UC and CD. Our study
      explored the genetic risk prediction in UC and CD, and may provide valuable
      insights into IBD therapy.

PMID- 22467261
TI  - Left atrial volume: clinical value revisited.
AB  - Left atrial (LA) volume and function are robust markers of cardiovascular risks
      and adverse cardiac outcomes. With advances in imaging technology, including
      tissue Doppler, strain, and strain rate imaging, we can now determine LA volume
      and function more precisely and this is anticipated to augment our ability to
      risk stratify, incremental to clinical risk profiling. There is increasing
      evidence that LA remodeling is treatable and is reversible. Serial LA volume and
      function assessment may provide a simple and quantifiable way of determining
      severity of risk and treatment impact. While reverse LA remodeling is expected to
      improve cardiac outcomes, data to confirm this remain forthcoming.

PMID- 22467263
TI  - Calculating pH-dependent free energy of proteins by using Monte Carlo protonation
      probabilities of ionizable residues.
AB  - Protein folding, stability, and function are usually influenced by pH. And free
      energy plays a fundamental role in analysis of such pH-dependent properties.
      Electrostatics-based theoretical framework using dielectric solvent continuum
      model and solving Poisson-Boltzmann equation numerically has been shown to be
      very successful in understanding the pH-dependent properties. However, in this
      approach the exact computation of pH-dependent free energy becomes impractical
      for proteins possessing more than several tens of ionizable sites (e.g. > 30),
      because exact evaluation of the partition function requires a summation over a
      vast number of possible protonation microstates. Here we present a method which
      computes the free energy using the average energy and the protonation
      probabilities of ionizable sites obtained by the well-established Monte Carlo
      sampling procedure. The key feature is to calculate the entropy by using the
      protonation probabilities. We used this method to examine a well-studied protein
      (lysozyme) and produced results which agree very well with the exact
      calculations. Applications to the optimum pH of maximal stability of proteins and
      protein-DNA interactions have also resulted in good agreement with experimental
      data. These examples recommend our method for application to the elucidation of
      the pH-dependent properties of proteins.

PMID- 22467265
TI  - Depression: a modifiable factor in fearful older fallers transitioning to
      frailty?
AB  - OBJECTIVE: Fear of falling is one of the most common fears among community
      dwelling older people and is as serious a health problem as falls themselves.
      Understanding fear of falling in fallers transitioning to frailty may help us
      identify effective strategies to reduce it in this already vulnerable group of
      older people. Our aim was to evaluate the psychological factors associated with
      fear of falling in a group of fallers transitioning to frailty when compared with
      robust or non-frail fallers. METHODS: Cross-sectional design where 301 fallers
      underwent assessment at the Technology Research for Independent Living Clinic in
      Dublin (http://www.trilcentre.org/) is seen. Fear of falling was measured using
      the Modified Falls Efficacy Scale, and frailty was measured using the Biological
      Syndrome Model. Psychological measures included assessment of anxiety,
      depression, loneliness, personality factors and cognition. RESULTS: Frailer
      fallers had increased fear of falling when compared with robust fallers (p <
      0.001). Age, female gender and lower cognitive scores were associated with
      greater fear of falling in the robust group. For frailer fallers, higher
      depression score was the only factor associated with fear of falling on
      multivariate analysis. The odds ratio of having case level depressive disorder
      (CESD-8 >= 4) if you were a frailer faller was significantly higher than if you
      were robust (OR = 2.6, CI 1.3-5.2, p = 0.006). CONCLUSION: Fallers at a
      transitional level of frailty may represent a particularly vulnerable group
      psychologically who would benefit most from interventional strategies with
      specific intervention components addressing depressive symptoms.

PMID- 22467264
TI  - Delineating nuclear reprogramming.
AB  - Nuclear reprogramming is described as a molecular switch, triggered by the
      conversion of one cell type to another. Several key experiments in the past
      century have provided insight into the field of nuclear reprogramming. Previously
      deemed impossible, this research area is now brimming with new findings and
      developments. In this review, we aim to give a historical perspective on how the
      notion of nuclear reprogramming was established, describing main experiments that
      were performed, including (1) somatic cell nuclear transfer, (2) exposure to cell
      extracts and cell fusion, and (3) transcription factor induced lineage switch.
      Ultimately, we focus on (4) transcription factor induced pluripotency, as
      initiated by a landmark discovery in 2006, where the process of converting
      somatic cells to a pluripotent state was narrowed down to four transcription
      factors. The conception that somatic cells possess the capacity to revert to an
      immature status brings about huge clinical implications including personalized
      therapy, drug screening and disease modeling. Although this technology has
      potential to revolutionize the medical field, it is still impeded by technical
      and biological obstacles. This review describes the effervescent changes in this
      field, addresses bottlenecks hindering its advancement and in conclusion, applies
      the latest findings to overcome these issues.

PMID- 22467266
TI  - Cancer among patients with diabetes, obesity and abnormal blood lipids: a
      population-based register study in Sweden.
AB  - OBJECTIVE: To study how the incidence of cancer is related to diabetes, obesity
      or abnormal blood lipids. METHODS: Diagnosis of diabetes, obesity or abnormal
      blood lipids was studied 0-10 years prior to the diagnosis of cancer in 19,756
      cases of cancer and in 147,324 controls matched regarding age, sex and domicile.
      RESULTS: Diabetes was significantly more common prior to diagnosis in patients
      with liver, pancreatic, colon and urinary tract/bladder cancer and in patients
      with breast cancer diagnosed with diabetes 0-4 years prior to the cancer
      diagnosis. A lower risk of diabetes was seen in patients with prostate carcinoma
      among individuals with diabetes diagnosed 5-10 years prior to the cancer
      diagnosis. The findings remained after adjusting for obesity and high blood
      lipids. Obesity was significantly more common in patients with endometrial, colon
      and kidney cancer and with breast cancer above the age of 60 years in those where
      obesity was diagnosed close to the diagnosis of cancer. High blood lipids were
      significantly more common in patients with ovarian cancer and less common in
      patients with breast cancer. CONCLUSIONS: The study confirms some previous
      findings concerning comorbidity and cancer and highlights some new ones.

PMID- 22467267
TI  - Mechanism of oxide layer growth during annealing of NiTi.
AB  - After annealing at 540 degrees C, NiTi is covered by a characteristic oxide layer
      with an Ni-containing outer and an Ni-free inner titanium oxide region. To
      elucidate details of the yet unclear formation process, samples were annealed in
      an atmosphere containing different oxygen isotopes at a time and analyzed by
      nondestructive ion beam techniques at different stages of the oxidation. During
      the heating stage, an oxygen permeable "low Ni" titanium oxide forms, and the
      oxide layer grows inward. Subsequently, when the annealing temperature of 540
      degrees C is reached, Ni-free stoichiometric titanium oxide forms and inhibits
      the transport of oxygen toward the bulk. Thus, the oxide layer growth changes to
      outward, and the final location of the reaction front between O and Ti is inside
      the oxide layer at the transition of "low Ni" oxide to "Ni-free" oxide.
      Consequently, the annealing conditions during inward oxide layer growth govern
      the surface properties, whereas the conditions during outward oxide layer growth
      are uncritical with respect to the surface properties. The findings are directly
      applicable to set the amount of surface Ni of NiTi devices, provide basis for
      detailed interpretation of experimental results involving annealing of NiTi, and
      can further respective modeling.

PMID- 22467268
TI  - Therapy with lenalidomide plus dexamethasone-induced bone formation in a patient
      with refractory multiple myeloma.
AB  - Bone disease is a major symptom of multiple myeloma, which results from excessive
      osteoclast activation and impaired osteoblast function. Novel antimyeloma agents,
      such as immunomodulatory drugs and bortezomib, alter bone metabolism in patients
      with this disease. However, recent studies have shown that bortezomib affects
      bone formation and healing, but immunomodulatory drugs do not. We report a case
      of refractory multiple myeloma that was treated with lenalidomide combined with
      dexamethasone (RD regimen). As a result, the patient's myeloma protein expression
      was markedly reduced, and her hematological profile was improved. However, the
      treatment also induced tetany by reducing her serum calcium and magnesium levels
      and elevating her alkaline phosphatase levels. In addition, conventional
      radiography and computed tomography detected osteosclerosis. These findings
      suggest that the RD regimen affects bone formation, possibly by activating
      osteoblasts. This is to our knowledge the first report to suggest that
      lenalidomide, an immunomodulatory drug, affects osteogenesis, at least in a
      certain subpopulation of patients with multiple myeloma.

PMID- 22467269
TI  - A mirror of two faces: Lin28 as a master regulator of both miRNA and mRNA.
AB  - Lin28 is an evolutionarily conserved RNA-binding protein that plays important
      roles in development, pluripotency, tumorigenesis, and metabolism. Emerging
      evidence suggests that the pleiotropic roles of Lin28 in the diverse
      physiological and pathological processes are mechanistically linked to its
      ability to modulate not only the biogenesis of miRNAs, particularly the let-7
      family miRNAs, but also the translation of mRNAs important for cell growth and
      metabolism. Let-7 negatively regulates the translation of oncogenes, cell cycle
      regulators, and metabolic pathway components. Lin28 relieves this repression by
      blocking the production of mature let-7. Lin28 binds to the terminal loops of let
      7 precursors, leading to inhibition of processing and the induction of
      uridylation and precursor degradation. Lin28 also is a direct translational
      regulator: it selectively binds to a cohort of mRNAs and stimulates their
      translation. Recent advances in our understanding of Lin28-mediated mechanisms of
      posttranscriptional regulation of gene expression reveal important roles of this
      protein in the fields of development, stem cells, metabolic diseases, and cancer.

PMID- 22467271
TI  - An optimized ultraviolet-A light photodetector with wide-range photoresponse
      based on ZnS/ZnO biaxial nanobelt.
AB  - A novel 1D/1D nanocomposite-based photodetector is successfully fabricated from
      high-crystalline ZnS/ZnO biaxial nanobelts for the first time. Optimized
      performance of the ZnS/ZnO nanobelt photodetector is much better than that of
      pure ZnS or ZnO nanostructures, with a wide-range UV-A light photoresponse, high
      sensitivity, and very fast response speed.

PMID- 22467270
TI  - Spatial pattern separation in cognitively normal young and older adults.
AB  - This study examined the ability of cognitively normal young adults (n = 30) and
      older adults (n = 30) to perform a delayed match-to-sample task involving varying
      degrees of spatial interference to assess spatial pattern separation. Each trial
      consisted of a sample phase followed by a choice phase. During the sample phase,
      a circle appeared briefly on a computer screen. The participant was instructed to
      remember the location of the circle on the screen. During the choice phase, two
      circles were displayed simultaneously, and the participant was asked to indicate
      which circle was in the same location as the sample phase circle. The two circles
      on choice phase trials were separated by one of four possible spatial
      separations: 0, 0.5, 1.0, and 1.5 cm. Smaller separations are likely to create
      increased overlap among memory representations, which may result in heightened
      interference and a greater need for pattern separation. Consistent with this
      hypothesis, performance increased as a function of increased spatial separation
      in both young and older adults. However, young adults outperformed older adults,
      suggesting that spatial pattern separation may be less efficient in older adults
      due to potential age-related changes in the dentate gyrus and CA3 hippocampal
      subregions. Older adults also were divided into older impaired and older
      unimpaired groups based on their performance on a standardized test of verbal
      memory. The older impaired group was significantly impaired relative to both the
      older unimpaired and young groups, suggesting that pattern separation deficits
      may be variable in older adults. The present findings may have important
      implications for designing behavioral interventions for older adults that
      structure daily living tasks to reduce interference, thus improving memory
      function.

PMID- 22467272
TI  - Affinity maturation of anti-TNF-alpha scFv with somatic hypermutation in non-B
      cells.
AB  - Activation-induced cytidine deaminase (AID) is required for the generation of
      antibody diversity through initiating both somatic hypermutation (SHM) and class
      switch recombination. A few research groups have successfully used the feature of
      AID for generating mutant libraries in directed evolution of target proteins in B
      cells in vitro. B cells, cultured in suspension, are not convenient for
      transfection and cloning. In this study, we established an AID-based mutant
      accumulation and sorting system in adherent human cells. Mouse AID gene was first
      transfected into the human non-small cell lung carcinoma H1299 cells, and a
      stable cell clone (H1299-AID) was selected. Afterwards, anti-hTNF-alpha scFv
      (ATscFv) was transfected into H1299-AID cells and ATscFv was displayed on the
      surface of H1299-AID cells. By 4-round amplification/flow cytometric sorting for
      cells with the highest affinities to hTNF-alpha, two ATscFv mutant gene clones
      were isolated. Compared with the wild type ATscFv, the two mutants were much more
      efficient in neutralizing cytotoxicity of hTNF-alpha. The results indicate that
      directed evolution by somatic hypermutation can be carried out in adherent non-B
      cells, which makes directed evolution in mammalian cells easier and more
      efficient.

PMID- 22467274
TI  - Impact of statin discontinuation on mortality in patients with rheumatoid
      arthritis: a population-based study.
AB  - OBJECTIVE: To evaluate the impact of statin discontinuation on cardiovascular
      disease (CVD) mortality and all-cause mortality in a population-based cohort of
      patients with rheumatoid arthritis (RA). METHODS: We conducted a population-based
      longitudinal study of RA patients with incident statin use followed from 1996 to
      2006 using administrative health data. Statin discontinuation was defined as
      persistent nonuse for >=3 months during the therapy course. Primary outcomes were
      mortality from all CVDs (CVD mortality) and secondary outcomes were deaths from
      all causes (all-cause mortality). Cox proportional hazards models with statin
      discontinuation as a time-dependent variable were used and multivariable models
      were adjusted for age, sex, comorbidities, and risk factors for mortality, and
      proxy indicators of RA severity. RESULTS: Over 16,144 person-years of followup in
      the cohort of 4,102 incident statin users, we documented 198 deaths due to CVD
      and 467 deaths overall. Adjusted hazard ratios for the association of statin
      discontinuation with death were 1.60 (95% confidence interval [95% CI] 1.15-2.23)
      for CVD mortality and 1.79 (95% CI 1.46-2.20) for all-cause mortality. The
      association between statin discontinuation and mortality outcomes was not
      modified by timing of the first statin prescription, age, and sex (P values for
      interaction >=0.29). CONCLUSION: These population-based data indicate that statin
      discontinuation in patients with RA is associated with an increased risk of death
      from CVD and all causes. Findings provide support for the importance of
      compliance with therapy in RA patients who are prescribed statins.

PMID- 22467273
TI  - Glycemic control and cardiovascular disease: what's a doctor to do?
AB  - Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality
      in individuals with diabetes mellitus. Moreover, rates of CVD mortality are two
      to four times higher in diabetes than in those without diabetes. It was
      conventional thinking that achieving near-normoglycemia would help reduce CVD
      risk and overall mortality in type 2 diabetes mellitus. Several recent large
      trials attempted to answer this question using a randomized control trial design
      with a conventional therapy and an intensive control arm. Surprisingly, these
      trials did not demonstrate neither mortality nor a CVD advantage with intensive
      glycemic control. Moreover, some studies (e.g., the ACCORD [Action to Control
      Cardiovascular Risk in Diabetes] study) showed increased mortality in the
      intensive control arm. In this review, our goal is to summarize the findings of
      the major trials in this field and to explore the potential reasons for why these
      trials had largely negative results. We conclude with some lessons that may be
      applied to the clinical management of patients with diabetes.

PMID- 22467275
TI  - An intersubunit disulfide bridge stabilizes the tetrameric nucleoside diphosphate
      kinase of Aquifex aeolicus.
AB  - The nucleoside diphosphate kinase (Ndk) catalyzes the reversible transfer of the
      gamma-phosphate from nucleoside triphosphate to nucleoside diphosphate. Ndks form
      hexamers or two types of tetramers made of the same building block, namely, the
      common dimer. The secondary interfaces of the Type I tetramer found in Myxococcus
      xanthus Ndk and of the Type II found in Escherichia coli Ndk involve the opposite
      sides of subunits. Up to now, the few available structures of Ndk from
      thermophiles were hexameric. Here, we determined the X-ray structures of four
      crystal forms of the Ndk from the hyperthermophilic bacterium Aquifex aeolicus
      (Aa-Ndk). Aa-Ndk displays numerous features of thermostable proteins and is made
      of the common dimer but it is a tetramer of Type I. Indeed, the insertion of
      three residues in a surface-exposed spiral loop, named the Kpn-loop, leads to the
      formation of a two-turn alpha-helix that prevents both hexamer and Type II
      tetramer assembly. Moreover, the side chain of the cysteine at position 133,
      which is not present in other Ndk sequences, adopts two alternate conformations.
      Through the secondary interface, each one forms a disulfide bridge with the
      equivalent Cys133 from the neighboring subunit. This disulfide bridge was
      progressively broken during X-ray data collection by radiation damage. Such
      crosslinks counterbalance the weakness of the common-dimer interface. A 40%
      decrease of the kinase activity at 60 degrees C after reduction and alkylation of
      the protein corroborates the structural relevance of the disulfide bridge on the
      tetramer assembly and enzymatic function.

PMID- 22467276
TI  - Accuracy and efficacy of thoracic pedicle screws in scoliosis with patient
      specific drill template.
AB  - With the rapid increase in the use of thoracic pedicle screws in scoliosis,
      accurate and safe placement of screw within the pedicle is a crucial step during
      the scoliosis surgery. To make thoracic pedicle screw placement safer various
      techniques are used, Patient-specific drill template with pre-planned trajectory
      has been thought as a promising solution, it is critical to assess the efficacy,
      safety profile with this technique. In this paper, we develop and validate the
      accuracy and safety of thoracic transpedicular screw placement with patient
      specific drill template technique in scoliosis. Patients with scoliosis requiring
      instrumentation were recruited. Volumetric CT scan was performed on each desired
      thoracic vertebra and a 3-D reconstruction model was generated from the CT scan
      data. The optimal screw size and orientation were determined and a drill template
      was designed with a surface that is the inverse of the posterior vertebral
      surface. The drill template and its corresponding vertebra were manufactured
      using rapid prototyping technique and tested for violations. The navigational
      template was sterilized and used intraoperatively to assist with the placement of
      thoracic screws. After surgery, the positions of the pedicle screws were
      evaluated using CT scan and graded for validation. This method showed its ability
      to customize the placement and the size of each pedicle screw based on the unique
      morphology of the thoracic vertebra. In all the cases, it was relatively very
      easy to manually place the drill template on the lamina of the vertebral body
      during the surgery. This method significantly reduces the operation time and
      radiation exposure for the members of the surgical team, making it a practical,
      simple and safe method. The potential use of such a navigational template to
      insert thoracic pedicle screws in scoliosis is promising. The use of surgical
      navigation system successfully reduced the perforation rate and insertion angle
      errors, demonstrating the clear advantage in safe and accurate pedicle screw
      placement of scoliosis surgery.

PMID- 22467277
TI  - Hepatic progenitor cells activation, fibrosis, and adipokines production in
      pediatric nonalcoholic fatty liver disease.
AB  - Hepatic progenitor cells (HPCs) play a major role in liver repair and
      regeneration. We evaluated HPC involvement in pediatric nonalcoholic fatty liver
      disease (pNAFLD). Thirty biopsies of consecutive children and adolescents with
      untreated NAFLD (19 with nonalcoholic steatohepatitis [NASH] and 11 without NASH)
      were studied using immunohistochemistry and immunofluorescence. HPCs and HPC
      expressing adipokines (e.g., adiponectin, resistin, and glucagon-like peptide 1
      [GLP-1]) were counted and correlated with steatosis, inflammation, hepatocyte
      ballooning, fibrosis, and NAFLD activity score (NAS). The HPC compartment was
      expanded in pNAFLD, especially in children with NASH, and was independently
      associated with degree of fibrosis (r = 0.303; P = 0.033). NASH livers were also
      characterized by increased hepatocyte apoptosis, cell-cycle arrest, and an
      expanded pool of intermediate hepatocytes. Adiponectin expression in HPCs of
      pNAFLD patients was down-regulated with respect to the healthy liver, and this
      expression was inversely correlated with NAS score (r = -0.792; P < 0.001) and
      steatosis (r = -0.769; P < 0.001). Resistin expression in HPCs increased in
      pNAFLD and was related to degree of fibrosis (r = 0.432; P < 0.05). GLP-1 was
      overexpressed in HPCs of pNAFLD patients, and GLP-1 expression was related to
      degree of steatosis (r = 0.577; P < 0.05) and NAS (r = 0.594; P < 0.01).
      CONCLUSIONS: HPC activation is involved in the response of the liver to oxidative
      stress in pNAFLD and is correlated with fibrosis and the progression toward NASH.
      HPCs express adiponectin, resistin, and GLP-1, which become available to resident
      liver cells and are strongly associated with the severity of NAFLD. These results
      may have important pathophysiological implications in the modulation of hepatic
      insulin resistance and the progression of liver injury.

PMID- 22467278
TI  - Automated methods for accurate determination of the critical velocity of packed
      bed chromatography.
AB  - Knowing the critical velocity (ucrit) of a chromatography column is an important
      part of process development as it allows the optimization of chromatographic flow
      conditions. The conventional flow step method for determining ucrit is prone to
      error as it depends heavily on human judgment. In this study, two automated
      methods for determining ucrit have been developed: the automatic flow step (AFS)
      method and the automatic pressure step (APS) method. In the AFS method, the
      column pressure drop is monitored upon application of automated incremental
      increases in flow velocity, whereas in the APS method the flow velocity is
      monitored upon application of automated incremental increases in pressure drop.
      The APS method emerged as the one with the higher levels of accuracy, efficiency
      and ease of application having the greater potential to assist defining the best
      operational parameters of a chromatography column.

PMID- 22467279
TI  - The correlation between pain-related behaviour and spinal microgliosis in four
      distinct models of peripheral neuropathy.
AB  - BACKGROUND: Peripheral nerve injury is associated with a spinal microglial
      response that has been correlated with the development of behaviours reflective
      of neuropathic pain. METHODS: To examine whether this phenomenon is generalizable
      to neuropathic pain of non-traumatic aetiology, this study investigated the
      association between spinal microgliosis and behavioural measures of neuropathic
      hypersensitivity and pain-related anxiety behaviour in four distinct rat models
      of peripheral neuropathic pain. These were traumatic neuropathy [L5 spinal nerve
      transection (SNT)], HIV-related neuropathies (either treatment with the
      antiretroviral drug Zalcitabine (ddC) or combination of perineural exposure to
      the HIV-gp120 protein and ddC treatment) and varicella zoster virus (VZV)
      infection. RESULTS AND CONCLUSION: Persistent mechanical hypersensitivity
      developed in all 'neuropathic' rats. However, spinal microgliosis, as measured by
      increased CD11b/c immunohistochemical staining and increased numbers of cells
      expressing CD11b measured by flow cytometry, was evident in the SNT and to a
      lesser extent in the HIV neuropathy models but not the VZV model. These results
      suggest that behavioural hypersensitivity and thigmotaxis can only be linked to a
      microglial response in certain models of neuropathy.

PMID- 22467280
TI  - In vivo biofunctionality comparison of different topographic PLLA scaffolds.
AB  - In this work, the in vivo biodegradation of, biocompatibility of, and host
      response to various topographic scaffolds were investigated. Randomly oriented
      fibrous poly(L-lactide) (PLLA) nanofibers were fabricated using the
      electrospinning technique. A PLLA scaffold was obtained by salt leaching. Both
      the electrospun PLLA nanofibers and the salt-leaching PLLA scaffolds formed three
      dimensional pore structures. Cytotoxicity studies, in which rat muscle-derived
      stem cells (rMDSCs) were grown on electrospun PLLA nanofibers or the salt
      leaching PLLA scaffolds, revealed that the rMDSCs cell count on the PLLA
      nanofibers was slightly higher than that on the salt-leaching PLLA scaffolds. An
      in vivo study was carried out by implanting the scaffolds subcutaneously into
      rats to test the biodegradation, biocompatibility, and host response at regular
      intervals over 0-4 weeks. The degradation of the PLLA nanofibers 1, 2, and 4
      weeks after initial implantation was more extensive than that observed for the
      salt-leaching PLLA scaffolds. PLLA nanofibers seeded the growth of larger fibrous
      tissue masses due to in vivo cellular infiltration into the randomly oriented
      fibrillar structures of the PLLA nanofibers. In addition, the inflammatory cell
      accumulation in PLLA nanofibers was lower than that in the salt-leaching PLLA
      scaffolds. These results indicate that the electrospun PLLA nanofibers may serve
      as a good scaffold to elicit fibrous cellular infiltration, to minimize host
      response, and to enhance tissue-scaffold integration.

PMID- 22467281
TI  - Investigation of thermal and temporal responses of ionization chambers in
      radiation dosimetry.
AB  - The ionization chamber is a primary dosimeter that is used in radiation
      dosimetry. Generally, the ion chamber response requires temperature/pressure
      correction according to the ideal gas law. However, this correction does not
      consider the thermal volume effect of chambers. The temporal and thermal volume
      effects of various chambers (CC01, CC13, NACP parallel-plate, PTW) with different
      wall and electrode materials have been studied in a water phantom. Measurements
      were done after heating the water with a suitable heating system, and chambers
      were submerged for a sufficient time to allow for temperature equilibrium.
      Temporal results show that all chambers equilibrate quickly in water. The
      equilibration time was between 3 and 5 min for all chambers. Thermal results show
      that all chambers expanded in response to heating except for the PTW, which
      contracted. This might be explained by the differences in the volumes of all
      chambers and also by the difference in wall material composition of PTW from the
      other chambers. It was found that the smallest chamber, CC01, showed the greatest
      expansion. The magnitude of the expansion was ~1, 0.8, and 0.9% for CC01, CC13,
      and parallel-plate chambers, respectively, in the temperature range of 295-320 K.
      The magnitude of the detected contraction was <0.3% for PTW in the same
      temperature range. For absolute dosimetry, it is necessary to make corrections
      for the ion chamber response, especially for small ion chambers like the CC01.
      Otherwise, room and water phantom temperatures should remain within a close
      range.

PMID- 22467282
TI  - Anatomic variants on computed tomography in congenital aural atresia.
AB  - OBJECTIVE: To report the prevalence of anatomic variants on computed tomography
      (CT) in congenital aural atresia (CAA) and external auditory canal stenosis
      (EACS). Anatomic variants included inferiorly displaced/obstructing tegmen
      mastoideum, malleus-incus complex (MIC) directly lateral to stapes, facial nerve
      obstruction of oval window (OW) or middle ear, and incudostapedial joint (ISJ)
      angle. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care children's
      hospital. SUBJECTS AND METHODS: An anatomic analysis of 130 CT scans (98
      children, 32 bilateral) of CAA/EACS, performed by a blinded neuroradiologist.
      Both Jahrsdoerfer's and new/modified anatomic considerations were graded in 32
      atresiaplasty and 66 nonsurgical patients. Surgical data were analyzed for
      anatomic correlations related to surgical findings. RESULTS: Prevalence of
      anatomic variants was as follows: 13% of the ears had mild inferior displacement
      of tegmen, 4% had a significantly obstructing tegmen, and 24% had MIC directly
      lateral to stapes. The facial nerve obstructed access to OW in 41% and middle ear
      in 21%. Six atresiaplasty patients were reported to have a large MIC obstructing
      stapes access with increased intraoperative difficulty in viewing and assessing
      the integrity and mobility of the ISJ and stapes. Five of these 6 (83%) were
      noted on CT scan. The mean ISJ angle was 101 degrees  (range, 51 degrees -155
      degrees ). CONCLUSION: A large obstructing MIC increases difficulty of
      atresiaplasty. Awareness of the presence of these anatomic variants is an aid in
      teaching temporal bone anatomy and may possibly influence the decision regarding
      atresiaplasty.

PMID- 22467283
TI  - Labyrinthine sequestrum: four case studies.
AB  - Labyrinthine sequestrum, a rare form of labyrinthitis, is highly distinct from
      the more commonly encountered labyrinthitis ossificans based on its unique
      clinical, radiologic, and histologic characteristics. The study included 4 such
      patients who had undergone clinical and laboratory investigations, computed
      tomography (CT), and magnetic resonance imaging (MRI) assessments followed by
      surgical procedures and pathological evaluation. Their major symptoms were
      otorrhea, otalgia, tinnitus, and profound hearing loss. Imaging studies showed an
      osteolytic soft mass with calcified debris in the inner ear, and the bony
      labyrinth was eroded partly or completely by granulation mass, with loss of bony
      morphology. Further pathological examination was coincident with inflammatory
      granulation tissue with some calcification or osseous tissue. The disease process
      is attributed to chronic osteomyelitis due to the presence of osteonecrosis.
      Prompt CT and MRI examinations and optimal therapeutic management facilitate
      definitive diagnosis and protect against fatal complications.

PMID- 22467284
TI  - A randomized double-blind crossover study of phase-shift sound therapy for
      tinnitus.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of the treatment
      of tinnitus with a phase-shifting pure tone to that of the same tone treatment
      without phase shifting. STUDY DESIGN: A double-blind crossover randomized
      controlled trial. SETTING: This study was conducted at the University Medical
      Center Groningen. SUBJECTS AND METHODS: Twenty-two patients with predominantly
      tonal tinnitus underwent both intervention and control treatments. Each treatment
      consisted of three 30-minute sessions in 1 week. The control treatment was
      identical to the intervention treatment, except that the stimulus was a pure tone
      without phase shifting. Questionnaires, tinnitus loudness match, and annoyance
      and loudness ratings were used to measure treatment effects. RESULTS: Pure-tone
      treatment and phase-shift treatment had no significant effect on tinnitus
      according to questionnaires (Tinnitus Handicap Index, Tinnitus Reaction
      Questionnaire, Hospital Anxiety and Depression Scale, and Maastricht
      Questionnaire), audiological matching procedures, and loudness and annoyance
      ratings of tinnitus. Furthermore, phase-shift treatment showed no additional
      significant improvement in comparison with pure-tone treatment. Changes in
      questionnaire scores due to pure-tone and the phase-shift treatment were
      correlated. CONCLUSION: On average across the group, both treatments failed to
      demonstrate a significant effect. Both treatments were beneficial for some
      patients. However, a positive effect was not demonstrated that could be
      attributed to the periodic shifting of the phase of the stimulus tone.

PMID- 22467285
TI  - Preoperative incidence of olfactory dysfunction in nasal surgery patients.
AB  - OBJECTIVE: Learn the incidence of olfactory dysfunction in preoperative patients
      prior to nasal surgery and compare with a control group of patients who are not
      going to have such surgery. Assess the usefulness of the coffee/tea
      differentiation test in assessing preoperative dysosmia. STUDY DESIGN:
      Prospective controlled cohort study. SETTING: Urban medical center. SUBJECTS AND
      METHODS: One hundred fifty-one adult patients (aged 18-65 years) whose olfactory
      function was tested using the Pocket Smell Test and a coffee/tea differentiation
      test. A failed test required missing at least 1 item on the card or failure to
      report a difference between tea and coffee. The statistical analysis using the t
      test and the Fisher exact test were calculated using MINITAB. RESULTS: The study
      group (n = 55) had 38% men and 62% women compared with 58% men and 42% women in
      the control group (n = 96). The incidence of dysosmia was 32% in the study group
      and 14% in the control group. In the study group, 34.5% of patients failed the
      Pocket Smell Test and 12.4% failed the coffee/tea differentiation test as
      compared with 12.4% and 0%, respectively, in the control group. CONCLUSION:
      Patients who are scheduled for nasal surgery for medical or cosmetic indications
      are more likely to suffer from olfactory dysfunction before surgical
      intervention. This should be taken into consideration when counseling patients
      regarding possible postoperative complications.

PMID- 22467286
TI  - Reevaluating the prognostic significance of age in differentiated thyroid cancer.
AB  - OBJECTIVE: To determine the impact of age on disease-specific survival in
      differentiated thyroid cancer. STUDY DESIGN: Retrospective analysis of a large
      population database. Setting Surveillance, Epidemiology, and End Results (SEER)
      database/multiple settings. SUBJECTS AND METHODS: The SEER database was examined
      to identify patients diagnosed with either papillary or follicular carcinoma of
      the thyroid between the years 1988 and 2003. Information obtained included
      patient age, sex, tumor type, size, extension, and nodal or distant metastases.
      Kaplan-Meier survival analyses were used to estimate disease-specific survival
      based on patient age range, and the log-rank test was used to assess for
      statistical differences between survival curves. A multivariate analysis was
      performed including the variables listed above to determine disease-specific
      hazard ratios of death for various age cutoffs. RESULTS: A total of 42,209
      patients were identified. Patients 45 years and older had significantly worse
      survival than younger patients (P < .0001). A significant decrease in disease
      specific survival was first seen in patients aged 35 years and older, and
      survival continued to steadily decrease with each additional decade of age (P <
      .001). Patients aged 35 years and older were 14 times more likely to die from
      differentiated thyroid cancer than patients younger than 35 years. CONCLUSION:
      Increasing age is associated with poorer survival in differentiated thyroid
      cancer. This relationship represents a continuum with an initial decrease in
      survival starting at age 35 years that continues to decline with further
      advancing age.

PMID- 22467287
TI  - The role of vestibular caloric tests in cochlear implantation.
AB  - OBJECTIVE: Vestibular function tests are often undertaken before cochlear
      implantation, in part to help select the side of surgery. The authors aim to
      determine whether implantation on the side of better vestibular function leads to
      greater perception of dizziness by patients than implantation on the side of
      worse or similar function. STUDY DESIGN: Historical cohort study. SETTING:
      Tertiary cochlear implantation center. SUBJECTS AND METHODS: The records of 177
      adult recipients of a unilateral cochlear implant were reviewed retrospectively
      in 2 groups. Group A included patients with an implant in the ear with worse or
      similar caloric responses. Group B included patients with an implant in the ear
      with the stronger caloric response. All patients underwent preoperative bithermal
      caloric testing: a clinically significant difference was defined by a 20% lateral
      canal paresis. They were assessed postoperatively by the Dizziness Handicap
      Inventory and supplementary questions. RESULTS: Fifty-seven percent of both
      groups reported dizziness in the first 7 days postoperatively. At 2 months, 20%
      of group A and 34% of group B experienced some dizziness. Fourteen percent of
      group A and 10% of group B felt that cochlear implantation had resulted in
      impaired balance. The Dizziness Handicap Inventory scores of 86% of group A
      (median score 0) and 76% of group B (median score 10) corresponded with low
      handicap. None of these results differed significantly between groups A and B.
      CONCLUSION: Although cochlear implantation may result in dizziness, it is almost
      always short-lived and mild, even when the ear with the stronger caloric response
      is implanted.

PMID- 22467288
TI  - Cohort profile: the Helsinki Health Study.
AB  - The Helsinki Health Study cohort was set up to enable longitudinal studies on the
      social and work related determinants of health and well-being, making use of self
      reported as well as objective register data. The target population is the staff
      of the City of Helsinki, Finland. Baseline data for the cohort were derived from
      questionnaire surveys conducted in 2000, 2001 and 2002 among employees reaching
      40, 45, 50, 55 or 60 years of age in each year. The number of responders at
      baseline was 8960 (80% women, response rate 67%). Additional age-based health
      examination data were available. A follow up survey was conducted in 2007
      yielding 7332 responders (response rate 83%). Measures of health include health
      behaviours, self-rated health, common mental disorders, functioning, pain, sleep
      problems, angina symptoms and major diseases. Social determinants include socio
      demographics, socio-economic circumstances, working conditions, social support,
      and work-family interface. Further register linkages include sickness absence,
      hospital discharge, prescribed drugs, and retirement updated at the end of 2010.
      The cohort allows comparisons with the Whitehall II study, London, UK, and the
      Japanese Civil Servants Study from western Japan. The cohort data are available
      for collaborative research at Hjelt Institute, Department of Public Health,
      University of Helsinki, Finland.

PMID- 22467289
TI  - The relationship between high blood glucose and socio-economic position in
      childhood and adulthood in Korea: findings from the Korean National Health and
      Nutrition Examination, 2007-09.
AB  - BACKGROUND: Unlike the older birth cohort (1943-65), the younger birth cohort
      (1966-79) has enjoyed much improved standards with dramatic developments in
      Korea. This article investigated the relationship between socio-economic position
      (SEP) and risk of high blood glucose, including impaired fasting glucose (IFG)
      and type 2 diabetes mellitus (T2D) by birth cohort. METHODS: Of the 11 830
      persons, 9792 persons aged 30-64 years participated in National Health and
      Nutrition Examination Surveys. We categorized four SEP groups based on education
      level in childhood and adulthood within two birth cohorts. High blood glucose
      included IFG (n = 2594) and T2D (n = 738). Odds ratio (OR) and 95% confidence
      interval (CI) were estimated by logistic regression. RESULTS: There was a
      significantly higher risk of high blood glucose in the younger cohort than in the
      older cohort. In the younger cohort, the ORs for males of declining SEP and of
      stable low SEP were OR: 1.50 (95% CI 1.12-2.00) and OR: 1.45 (95% CI 1.08-1.93),
      respectively. After adjustments, corresponding ORs were 1.47 (95% CI 1.09-1.98)
      and 1.54 (95% CI 1.14-2.08), respectively. In younger women, the corresponding
      ORs were 1.68 (95% CI 1.17-2.41) and 1.87 (95% CI 1.30-2.69), respectively;
      however, obesity attenuated the former relationship. For women in the older
      cohort, this inverse relationship was found only among those with a stable low
      SEP (OR 1.31, 95% CI 1.04-1.66); no significance was found after adjustments.
      There was no significant inverse relationship in the older cohort for men.
      CONCLUSIONS: The relationship between lower SEP and elevated risk of high blood
      glucose was stronger in the younger birth cohort, and obesity attenuated this
      inverse relationship in women only.

PMID- 22467290
TI  - Alcohol imagery and branding, and age classification of films popular in the UK.

PMID- 22467291
TI  - Impact of occupational carcinogens on lung cancer risk in a general population.
AB  - BACKGROUND: Exposure to occupational carcinogens is an important preventable
      cause of lung cancer. Most of the previous studies were in highly exposed
      industrial cohorts. Our aim was to quantify lung cancer burden attributable to
      occupational carcinogens in a general population. METHODS: We applied a new job
      exposure matrix (JEM) to translate lifetime work histories, collected by personal
      interview and coded into standard job titles, into never, low and high exposure
      levels for six known/suspected occupational lung carcinogens in the Environment
      and Genetics in Lung cancer Etiology (EAGLE) population-based case-control study,
      conducted in Lombardy region, Italy, in 2002-05. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated in men (1537 cases and 1617 controls),
      by logistic regression adjusted for potential confounders, including smoking and
      co-exposure to JEM carcinogens. The population attributable fraction (PAF) was
      estimated as impact measure. RESULTS: Men showed an increased lung cancer risk
      even at low exposure to asbestos (OR: 1.76; 95% CI: 1.42-2.18), crystalline
      silica (OR: 1.31; 95% CI: 1.00-1.71) and nickel-chromium (OR: 1.18; 95% CI: 0.90
      1.53); risk increased with exposure level. For polycyclic aromatic hydrocarbons,
      an increased risk (OR: 1.64; 95% CI: 0.99-2.70) was found only for high
      exposures. The PAFs for any exposure to asbestos, silica and nickel-chromium were
      18.1, 5.7 and 7.0%, respectively, equivalent to an overall PAF of 22.5% (95% CI:
      14.1-30.0). This corresponds to about 1016 (95% CI: 637-1355) male lung cancer
      cases/year in Lombardy. CONCLUSIONS: These findings support the substantial role
      of selected occupational carcinogens on lung cancer burden, even at low
      exposures, in a general population.

PMID- 22467293
TI  - The poetics and statistics of the average life: from ASJ Tessimond to Health and
      Demographic Surveillance Systems.

PMID- 22467292
TI  - The association between waist circumference and risk of mortality considering
      body mass index in 65- to 74-year-olds: a meta-analysis of 29 cohorts involving
      more than 58 000 elderly persons.
AB  - BACKGROUND: For the elderly, the association between waist circumference (WC) and
      mortality considering body mass index (BMI) remains unclear, and thereby also the
      evidence base for using these anthropometric measures in clinical practice. This
      meta-analysis examined the association between WC categories and (cause-specific)
      mortality within BMI categories. Furthermore, the association of continuous WC
      with lowest and increased mortality risks was examined. METHODS: Age- and smoking
      adjusted relative risks (RRs) of mortality associated with WC-BMI categories and
      continuous WC (including WC and WC(2)) were calculated by the investigators and
      pooled by means of random-effects models. RESULTS: During a 5-year-follow-up of
      32 678 men and 25 931 women, we ascertained 3318 and 1480 deaths, respectively. A
      large WC (men: >=102 cm, women: >=88 cm) was associated with increased all-cause
      mortality RRs for those in the 'healthy' weight {1.7 [95% confidence interval
      (CI): 1.2-2.2], 1.7 (95% CI: 1.3-2.3)}, overweight [1.1(95% CI: 1.0-1.3), 1.4
      (95%: 1.1-1.7)] and obese [1.1 (95% CI: 1.0-1.3), 1.6 (95% CI: 1.3-1.9)] BMI
      category compared with the 'healthy' weight (20-24.9 kg/m(2)) and a small WC (<94
      cm, men; <80 cm, women) category. Underweight was associated with highest all
      cause mortality RRs in men [2.2 (95% CI: 1.8-2.8)] and women [2.3 (95% CI: 1.8
      3.1]. We found a J-shaped association for continuous WC with all-cause,
      cardiovascular (CVD) and cancer, and a U-shaped association with respiratory
      disease mortality (P < 0.05). An all-cause (CVD) mortality RR of 2.0 was
      associated with a WC of 132 cm (123 cm) in men and 116 cm (105 cm) in women.
      CONCLUSIONS: Our results showed increased mortality risks for elderly people with
      an increased WC-even across BMI categories- and for those who were classified as
      'underweight' using BMI. The results provide a solid basis for re-evaluation of
      WC cut-points in ageing populations.

PMID- 22467297
TI  - 4-(N,N-dimethylamino)pyridine-embedded nanoporous conjugated polymer as a highly
      active heterogeneous organocatalyst.
AB  - We report herein for the first time the incorporation of a versatile
      organocatalyst, 4-(N,N-dimethylamino)pyridine (DMAP), into the network of a
      nanoporous conjugated polymer (NCP) by the "bottom-up" approach. The resulting
      DMAP-NCP material possesses highly concentrated and homogeneously distributed
      DMAP catalytic sites (2.02 mmol  g(-1)). DMAP-NCP also exhibits enhanced
      stability and permanent porosity due to the strong covalent linkage and the
      rigidity of the "bottom-up" monomers. As a result, DMAP-NCP shows excellent
      catalytic activity in the acylation of alcohols with yields of 92-99 %. The DMAP
      NCP catalyst could be easily recovered from the reaction mixture and reused in at
      least 14 consecutive cycles without measurable loss of activity. Moreover, the
      catalytic acylation reaction could be performed under neat and continuous-flow
      conditions for at least 536 h of continuous work with the same catalyst activity.

PMID- 22467296
TI  - Novel animal models of pediatric epilepsy.
AB  - When mimicking epileptic processes in a laboratory setting, it is important to
      understand the differences between experimental models of seizures and epilepsy.
      Because human epilepsy is defined by the appearance of multiple spontaneous
      recurrent seizures, the induction of a single acute seizure without recurrence
      does not constitute an adequate epilepsy model. Animal models of epilepsy might
      be useful for various tasks. They allow for the investigation of
      pathophysiological mechanisms of the disease, the evaluation, or the development
      of new antiepileptic treatments, and the study of the consequences of recurrent
      seizures and neurological and psychiatric comorbidities. Although clinical
      relevance is always an issue, the development of models of pediatric epilepsies
      is particularly challenging due to the existence of several key differences in
      the dynamics of human and rodent brain maturation. Another important
      consideration in modeling pediatric epilepsy is that "children are not little
      adults," and therefore a mere application of models of adult epilepsies to the
      immature specimens is irrelevant. Herein, we review the models of pediatric
      epilepsy. First, we illustrate the differences between models of pediatric
      epilepsy and models of the adulthood consequences of a precipitating insult in
      early life. Next, we focus on new animal models of specific forms of epilepsies
      that occur in the developing brain. We conclude by emphasizing the deficiencies
      in the existing animal models and the need for several new models.

PMID- 22467298
TI  - Distinct contributions of human hippocampal theta to spatial cognition and
      anxiety.
AB  - Current views of the hippocampus assign this structure, and its prominent theta
      rhythms, a key role in both cognition and affect. We studied this duality of
      function in humans, where no direct evidence exists. Whole-head
      magnetoencephalographic (MEG) data were recorded to measure theta activity while
      healthy participants (N = 25) navigated two virtual Morris water mazes, one in
      which they risked receiving aversive shocks without warning to induce anxiety and
      one in which they were safe from shocks. Results showed that threat of shock
      elevated anxiety level and enhanced navigation performance as compared to the
      safe condition. MEG source analyses revealed that improved navigation performance
      during threat was preferentially associated with increased left septal
      (posterior) hippocampal theta (specifically 4-8 Hz activity), replicating
      previous research that emphasizes a predominant role of the septal third of the
      hippocampus in spatial cognition. Moreover, increased self-reported anxiety
      during threat was preferentially associated with increased left temporal
      (anterior) hippocampal theta (specifically 2-6 Hz activity), consistent with this
      region's involvement in mediating conditioned and innate fear. Supporting
      contemporary theory, these findings highlight simultaneous involvement of the
      human hippocampus in spatial cognition and anxiety, and clarify their distinct
      correlates.

PMID- 22467299
TI  - Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective.
AB  - Defining the cellular electrophysiological mechanisms for ventricular
      tachyarrhythmias is difficult, given the wide array of potential mechanisms,
      ranging from abnormal automaticity to various types of reentry and kk activity.
      The degree of difficulty is increased further by the fact that any particular
      mechanism may be influenced by the evolving ionic and anatomic environments
      associated with many forms of heart disease. Consequently, static measures of a
      single electrophysiological characteristic are unlikely to be useful in
      establishing mechanisms. Rather, the dynamics of the electrophysiological
      triggers and substrates that predispose to arrhythmia development need to be
      considered. Moreover, the dynamics need to be considered in the context of a
      system, one that displays certain predictable behaviors, but also one that may
      contain seemingly stochastic elements. It also is essential to recognize that
      even the predictable behaviors of this complex nonlinear system are subject to
      small changes in the state of the system at any given time. Here we briefly
      review some of the short-, medium-, and long-term alterations of the
      electrophysiological substrate that accompany myocardial disease and their
      potential impact on the initiation and maintenance of ventricular arrhythmias. We
      also provide examples of cases in which small changes in the electrophysiological
      substrate can result in rather large differences in arrhythmia outcome. These
      results suggest that an interrogation of cardiac electrical dynamics is required
      to provide a meaningful assessment of the immediate risk for arrhythmia
      development and for evaluating the effects of putative antiarrhythmic
      interventions.

PMID- 22467300
TI  - Mice lacking macrophage 12/15-lipoxygenase are resistant to experimental
      hypertension.
AB  - In mouse arteries, Alox15 [leukocyte-type 12/15-lipoxygenase (LO)] is assumed to
      regulate vascular function by metabolizing arachidonic acid (AA) to dilator
      eicosanoids that mediate the endothelium-dependent relaxations to AA and
      acetylcholine (ACh). We used Alox15(-/-) mice, made by targeted disruption of the
      Alox15 gene, to characterize its role in the regulation of blood pressure and
      vascular tone. Systolic blood pressures did not differ between wild-type (WT) and
      Alox15(-/-) mice between 8-12 wk of age, but Alox15(-/-) mice exhibited
      resistance toward both N(G)-nitro-L-arginine-methyl ester (L-NAME)- and
      deoxycorticosterone acetate (DOCA)/high-salt-induced hypertension. ACh relaxed
      mesenteric arteries and abdominal aortas of WT and Alox15(-/-) mice to an
      identical extent. The LO inhibitor nordihydroguaiaretic acid attenuated the ACh
      relaxations by 35% in arteries from both WT and Alox15(-/-) mice. Reverse-phase
      HPLC analysis of [(14)C]AA metabolites in aorta and peritoneal macrophages (PM)
      revealed differences. Unlike PM, aorta tissue did not produce detectable amounts
      of 15-hydroxyeicosatetraenoic acid. Although Alox15 mRNA was detected in aorta,
      high-resolution gel electrophoresis with immunodetection revealed no Alox15
      protein expression. Unlike aorta, Alox15 protein was detected in PM, intestine,
      fat, lung, spleen, and skin from WT, but not Alox15(-/-), mice. Injection of WT
      PM, a primary source of Alox15 protein, into Alox15(-/-) mice abolished their
      resistance toward L-NAME-induced hypertension. On the other hand, WT mice
      acquired resistance to L-NAME-induced hypertension after depletion of macrophages
      by clodronate injection. These studies indicate that Alox15 is involved in
      development of experimental hypertension by altering macrophage functions but not
      via synthesis of the vasoactive LO metabolites in mouse arteries.

PMID- 22467301
TI  - Refractoriness of sarcoplasmic reticulum Ca2+ release determines Ca2+ alternans
      in atrial myocytes.
AB  - Cardiac alternans is a recognized risk factor for cardiac arrhythmia and sudden
      cardiac death. At the cellular level, Ca(2+) alternans appears as cytosolic
      Ca(2+) transients of alternating amplitude at regular beating frequency. Cardiac
      alternans is a multifactorial process but has been linked to disturbances in
      intracellular Ca(2+) regulation. In atrial myocytes, we tested the role of
      voltage-gated Ca(2+) current, sarcoplasmic reticulum (SR) Ca(2+) load, and
      restitution properties of SR Ca(2+) release for the occurrence of pacing-induced
      Ca(2+) alternans. Voltage-clamp experiments revealed that peak Ca(2+) current was
      not affected during alternans, and alternans of end-diastolic SR Ca(2+) load,
      evaluated by application of caffeine or measured directly with an intra-SR
      fluorescent Ca(2+) indicator (fluo-5N), were not a requirement for cytosolic
      Ca(2+) alternans. Restitution properties and kinetics of refractoriness of Ca(2+)
      release after activation during alternans were evaluated by four different
      approaches: measurements of 1) the delay (latency) of occurrence of spontaneous
      global Ca(2+) releases and 2) Ca(2+) spark frequency, both during rest after a
      large and small alternans Ca(2+) transient; 3) the magnitude of premature action
      potential-induced Ca(2+) transients after a large and small beat; and 4) the
      efficacy of a photolytically induced Ca(2+) signal (Ca(2+) uncaging from DM
      nitrophen) to trigger additional Ca(2+) release during alternans. The results
      showed that the latency of global spontaneous Ca(2+) release was prolonged and
      Ca(2+) spark frequency was decreased after the large Ca(2+) transient during
      alternans. Furthermore, the restitution curve of the Ca(2+) transient elicited by
      premature action potentials or by photolysis-induced Ca(2+) release from the SR
      lagged behind after a large-amplitude transient during alternans compared with
      the small-amplitude transient. The data demonstrate that beat-to-beat alternation
      of the time-dependent restitution properties and refractory kinetics of the SR
      Ca(2+) release mechanism represents a key mechanism underlying cardiac alternans.

PMID- 22467302
TI  - Role of KATP channel in electrical depression and asystole during long-duration
      ventricular fibrillation in ex vivo canine heart.
AB  - Long-duration ventricular fibrillation (LDVF) in the globally ischemic heart is
      characterized by transmurally heterogeneous decline in ventricular fibrillation
      rate (VFR), emergence of inexcitable regions, and eventual global asystole. Rapid
      loss of both local and global excitability is detrimental to successful
      defibrillation and resuscitation during cardiac arrest. We sought to assess the
      role of the ATP-sensitive potassium current (I(KATP)) in the timing and spatial
      pattern of electrical depression during LDVF in a structurally normal canine
      heart. We analyzed endo-, mid-, and epicardial unipolar electrograms and
      epicardial optical recordings in the left ventricle of isolated canine hearts
      during 10 min of LDVF in the absence (control) and presence of an I(KATP) blocker
      glybenclamide (60 MUM). In all myocardial layers, average VFR was the same or
      higher in glybenclamide-treated than in control hearts. The difference increased
      with time of LDVF and was overall significant in all layers (P < 0.05). However,
      glybenclamide did not significantly affect the transmural VFR gradient. In
      epicardial optical recordings, glybenclamide shortened diastolic intervals,
      prolonged action potential duration, and decreased the percentage of inexcitable
      area (all differences P < 0.001). During 10 min of LDVF, asystole occurred in
      55.6% of control and none of glybenclamide-treated hearts (P < 0.05). In three
      hearts paced after the onset of asystole, there was no response to LV epicardial
      or atrial pacing. In structurally normal canine hearts, I(KATP) opening during
      LDVF is a major factor in the onset of local and global inexcitability, whereas
      it has a limited role in overall deceleration of VFR and the transmural VFR
      gradient.

PMID- 22467303
TI  - Contractile parameters and occurrence of alternans in isolated rat myocardium at
      supra-physiological stimulation frequency.
AB  - The cardiac refractory period prevents the heart from tetanic activation that is
      typically used in noncardiac striated muscle tissue. To what extent the
      refractory period prevents successive action potentials to activate the
      excitation-contraction coupling process and contractile machinery at supra
      physiological rates, such as those present during ventricular fibrillation, is
      unknown. Using multicellular trabeculae isolated from rat hearts, we studied
      amplitude and kinetics of contraction at rates well above the normal in vivo rat
      heart range. We show that even at twice the maximal heart rate of the rat, little
      or no mechanical instability is observed; twitch contractions are at steady
      state, albeit with an elevated active diastolic force. Although the amplitude of
      contraction increased within in vivo heart rates (positive force-frequency
      response), at frequencies beyond the maximal heart rate (10-30 Hz) a steady
      decline of contractile amplitude is observed. Not until 30 Hz do the majority of
      the isolated muscle preparations show mechanical alternans, where strong and weak
      beats alternate. Interestingly, unlike striated limb skeletal muscle, fusing of
      twitch contractions did not cause a continuous increase in peak force: at
      frequencies of 10 Hz and above, systolic force declines with relatively little
      elevation in diastolic force. Contractile kinetics continued to accelerate, from
      1 Hz up to 30 Hz, whereas the relative speed of contraction and relaxation
      remained closely coupled, reflected by a singular linear relationship between the
      maximal and minimal derivative of force (dF/dt). We conclude that cardiac muscle
      can produce mechanically stable steady-state contractions at supra-physiological
      pacing rates, while these contractions continue to decline in amplitude and
      increase in diastolic force past maximal heart rate.

PMID- 22467304
TI  - Effects of increased preload on the force-frequency response and contractile
      kinetics in early stages of cardiac muscle hypertrophy.
AB  - Numerous studies have aimed to elucidate markers for the onset of decompensatory
      hypertrophy and heart failure in vivo and in vitro. Alterations in the force
      frequency relationship are commonly used as markers for heart failure with a
      negative staircase being a hallmark of decompensated cardiac function. Here we
      aim to determine the functional and molecular alterations in the very early
      stages of compensatory hypertrophy through analysis of the force-frequency
      relationship, using a novel isolated muscle culture system that allows assessment
      of force-frequency relationship during the development of hypertrophy. New
      Zealand white male rabbit trabeculae excised from the right ventricular free wall
      were utilized for all experiments. Briefly, muscles held at constant preload and
      contracting isometrically were stimulated to contract in culture for 24 h, and in
      a subset up to 48 h. We found that, upon an increase in the preload and
      maintaining the muscles in culture for up to 24 h, there was an increase in
      baseline force produced by isolated trabeculae over time. This suggests a gradual
      compensatory response to the impact of increased preload. Temporal analysis of
      the force-frequency response during this progression revealed a significant
      blunting (at 12 h) and then reversal of the positive staircase as culture time
      increased (at 24 h). Phosphorylation analysis revealed a significant decrease in
      desmin and troponin (Tn)I phosphorylation from 12 to 24 h in culture. These
      results show that even very early on in the compensatory hypertrophy state, the
      force-frequency relationship is already affected. This effect on force-frequency
      relationship may, in addition to protein expression changes, be partially
      attributed to the alterations in myofilament protein phosphorylation.

PMID- 22467305
TI  - Acute inhibition of GSK causes mitochondrial remodeling.
AB  - Recent data have shown that cardioprotection can result in the import of specific
      proteins into the mitochondria in a process that involves heat shock protein 90
      (HSP90) and is blocked by geldanamycin (GD), a HSP90 inhibitor. To test the
      hypothesis that an alteration in mitochondrial import is a more widespread
      feature of cardioprotection, in this study, we used a broad-based proteomics
      approach to investigate changes in the mitochondrial proteome following
      cardioprotection induced by inhibition of glycogen synthase kinase (GSK)-3.
      Mitochondria were isolated from control hearts, and hearts were perfused with the
      GSK inhibitor SB 216763 (SB) for 15 min before isolation of mitochondria.
      Mitochondrial extracts from control and SB-perfused hearts were labeled with
      isotope tags for relative and absolute quantification (iTRAQ), and differences in
      mitochondrial protein levels were determined by mass spectrometry. To test for
      the role of HSP90-mediated protein import, hearts were perfused in the presence
      and absence of GD for 15 min before perfusion with SB followed by mitochondrial
      isolation and iTRAQ labeling. We confirmed that treatment with GD blocked the
      protection afforded by SB treatment in a protocol of 20 min of ischemia and 40
      min of reperfusion. We found 16 proteins that showed an apparent increase in the
      mitochondrial fraction following SB treatment. GD treatment significantly blocked
      the SB-mediated increase in mitochondrial association for five of these proteins,
      which included annexin A6, vinculin, and pyruvate kinase. We also found that SB
      treatment resulted in a decrease in mitochondrial content of eight proteins, of
      which all but two are established mitochondrial proteins. To confirm a role for
      mitochondrial import versus a change in protein synthesis and/or degradation, we
      measured changes in these proteins in whole cell extracts. Taken together, these
      data show that SB leads to a remodeling of the mitochondrial proteome that is
      partially GD sensitive.

PMID- 22467306
TI  - Angiotensin-(1-7) attenuates hypertension in exercise-trained renal hypertensive
      rats.
AB  - Angiotensin-(1-7) [ANG-(1-7)] plays a counterregulatory role to angiotensin II in
      the renin-angiotensin system. In trained spontaneous hypertensive rats, Mas
      expression and protein are upregulated in ventricular tissue. Therefore, we
      examined the role of ANG-(1-7) on cardiac hemodynamics, cardiac functions, and
      cardiac remodeling in trained two-kidney one-clip hypertensive (2K1C) rats. For
      this purpose, rats were divided into sedentary and trained groups. Each group
      consists of sham and 2K1C rats with and without ANG-(1-7) infusion. Swimming
      training was performed for 1 h/day, 5 days/wk for 4 wk following 1 wk of swimming
      training for acclimatization. 2K1C rats showed moderate hypertension and left
      ventricular hypertrophy without changing left ventricular function. Chronic
      infusion of ANG-(1-7) attenuated hypertension and cardiac hypertrophy only in
      trained 2K1C rats but not in sedentary 2K1C rats. Chronic ANG-(1-7) treatment
      significantly attenuated increases in myocyte diameter and cardiac fibrosis
      induced by hypertension in only trained 2K1C rats. The Mas receptor, ANG II type
      2 receptor protein, and endothelial nitric oxide synthase phosphorylation in
      ventricles were upregulated in trained 2K1C rats. In conclusion, chronic infusion
      of ANG-(1-7) attenuates hypertension in trained 2K1C rats.

PMID- 22467307
TI  - The polysulfide diallyl trisulfide protects the ischemic myocardium by
      preservation of endogenous hydrogen sulfide and increasing nitric oxide
      bioavailability.
AB  - Diallyl trisulfide (DATS), a polysulfide constituent found in garlic oil, is
      capable of the release of hydrogen sulfide (H(2)S). H(2)S is a known
      cardioprotective agent that protects the heart via antioxidant, antiapoptotic,
      anti-inflammatory, and mitochondrial actions. Here, we investigated DATS as a
      stable donor of H(2)S during myocardial ischemia-reperfusion (MI/R) injury in
      vivo. We investigated endogenous H(2)S levels, infarct size, postischemic left
      ventricular function, mitochondrial respiration and coupling, endothelial nitric
      oxide (NO) synthase (eNOS) activation, and nuclear E2-related factor (Nrf2)
      translocation after DATS treatment. Mice were anesthetized and subjected to a
      surgical model of MI/R injury with and without DATS treatment (200 MUg/kg). Both
      circulating and myocardial H(2)S levels were determined using chemiluminescent
      gas chromatography. Infarct size was measured after 45 min of ischemia and 24 h
      of reperfusion. Troponin I release was measured at 2, 4, and 24 h after
      reperfusion. Cardiac function was measured at baseline and 72 h after reperfusion
      by echocardiography. Cardiac mitochondria were isolated after MI/R, and
      mitochondrial respiration was investigated. NO metabolites, eNOS phosphorylation,
      and Nrf2 translocation were determined 30 min and 2 h after DATS administration.
      Myocardial H(2)S levels markedly decreased after I/R injury but were rescued by
      DATS treatment (P < 0.05). DATS administration significantly reduced infarct size
      per area at risk and per left ventricular area compared with control (P < 0.001)
      as well as circulating troponin I levels at 4 and 24 h (P < 0.05). Myocardial
      contractile function was significantly better in DATS-treated hearts compared
      with vehicle treatment (P < 0.05) 72 h after reperfusion. DATS reduced
      mitochondrial respiration in a concentration-dependent manner and significantly
      improved mitochondrial coupling after reperfusion (P < 0.01). DATS activated eNOS
      (P < 0.05) and increased NO metabolites (P < 0.05). DATS did not appear to
      significantly induce the Nrf2 pathway. Taken together, these data suggest that
      DATS is a donor of H(2)S that can be used as a cardioprotective agent to treat
      MI/R injury.

PMID- 22467308
TI  - Enhanced sensitivity of aged fibrotic hearts to angiotensin II- and hypokalemia
      induced early afterdepolarization-mediated ventricular arrhythmias.
AB  - Unlike young hearts, aged hearts are highly susceptible to early
      afterdepolarization (EAD)-mediated ventricular fibrillation (VF). This
      differential may result from age-related structural remodeling (fibrosis) or
      electrical remodeling of ventricular myocytes or both. We used optical mapping
      and microelectrode recordings in Langendorff-perfused hearts and patch-clamp
      recordings in isolated ventricular myocytes from aged (24-26 mo) and young (3-4
      mo) rats to assess susceptibility to EADs and VF during either oxidative stress
      with ANG II (2 MUM) or ionic stress with hypokalemia (2.7 mM). ANG II caused EAD
      mediated VF in 16 of 19 aged hearts (83%) after 32 +/- 7 min but in 0 of 9 young
      hearts (0%). ANG II-mediated VF was suppressed with KN-93 (Ca(2+)/calmodulin
      dependent kinase inhibitor) and the reducing agent N-acetylcysteine. Hypokalemia
      caused EAD-mediated VF in 11 of 11 aged hearts (100%) after 7.4 +/- 0.4 min. In
      14 young hearts, however, VF did not occur in 6 hearts (43%) or was delayed in
      onset (31 +/- 22 min, P < 0.05) in 8 hearts (57%). In patch-clamped myocytes, ANG
      II and hypokalemia (n = 6) induced EADs and triggered activity in both age groups
      (P = not significant) at a cycle length of >0.5 s. When myocytes of either age
      group were coupled to a virtual fibroblast using the dynamic patch-clamp
      technique, EADs arose in both groups at a cycle length of <0.5 s. Aged ventricles
      had significantly greater fibrosis and reduced connexin43 gap junction density
      compared with young hearts. The lack of differential age-related sensitivity at
      the single cell level in EAD susceptibility indicates that increased ventricular
      fibrosis in the aged heart plays a key role in increasing vulnerability to VF
      induced by oxidative and ionic stress.

PMID- 22467309
TI  - Shear stress modulates RAGE-mediated inflammation in a model of diabetes-induced
      metabolic stress.
AB  - Atherosclerosis occurs preferentially at sites of disturbed blood flow despite
      the influence of risk factors contributing to systemic inflammation. The receptor
      for advanced glycation endproducts (RAGE) is a prominent mediator of inflammation
      in diabetes that is upregulated in atherosclerotic plaques. Our goal was to
      elucidate a role for arterial hemodynamics in the regulation of RAGE expression
      and activity. Endothelial RAGE expression was elevated at sites of flow
      disturbance in the aortas of healthy swine. To demonstrate a direct role for
      physiological shear stress (SS) in modulating RAGE expression, human aortic
      endothelial cells (HAEC) were exposed to high SS (HSS; 15 dyn/cm(2)), which
      downregulated RAGE by fourfold, or oscillatory SS (OSS; 0 +/- 5 dyn/cm(2)), which
      upregulated RAGE by threefold, compared with static culture at 4 h. In a model of
      diabetes-induced metabolic stress, HAEC were chronically conditioned under high
      glucose (25 mM) and then simultaneously stimulated with TNF-alpha (0.5 ng/ml) and
      the RAGE ligand high mobility group box 1 (HMGB1). A 50% increase in VCAM-1
      expression over TNF-alpha was associated with increased cytoplasmic and
      mitochondrial reactive oxygen species and NF-kappaB activity. This increase was
      RAGE-specific and NADPH oxidase dependent. In activated HAEC, OSS amplified HMGB1
      induced VCAM-1 (3-fold) and RAGE (1.6-fold) expression and proportionally
      enhanced monocyte adhesion to HAEC in a RAGE-dependent manner, while HSS
      mitigated these increases to the level of TNF-alpha alone. We demonstrate that SS
      plays a fundamental role in regulating RAGE expression and inflammatory responses
      in the endothelium. These findings may provide mechanistic insight into how
      diabetes accelerates the nonrandom distribution of atherosclerosis in arteries.

PMID- 22467310
TI  - Increases in intracellular sodium activate transcription and gene expression via
      the salt-inducible kinase 1 network in an atrial myocyte cell line.
AB  - Cardiac hypertrophy (CH) generally occurs as the result of the sustained
      mechanical stress caused by elevated systemic arterial blood pressure (BP).
      However, in animal models, elevated salt intake is associated with CH even in the
      absence of significant increases in BP. We hypothesize that CH is not exclusively
      the consequence of mechanical stress but also of other factors associated with
      elevated BP such as abnormal cell sodium homeostasis. We examined the effect of
      small increases in intracellular sodium concentration ([Na(+)](i)) on
      transcription factors and genes associated with CH in a cardiac cell line.
      Increases in [Na(+)](i) led to a time-dependent increase in the expression levels
      of mRNA for natriuretic peptide and myosin heavy chain genes and also increased
      myocyte enhancer factor (MEF)2/nuclear factor of activated T cell (NFAT)
      transcriptional activity. Increases in [Na(+)](i) are associated with activation
      of salt-inducible kinase 1 (snflk-1, SIK1), a kinase known to be critical for
      cardiac development. Moreover, increases in [Na(+)](i) resulted in increased SIK1
      expression. Sodium did not increase MEF2/NFAT activity or gene expression in
      cells expressing a SIK1 that lacked kinase activity. The mechanism by which SIK1
      activated MEF2 involved phosphorylation of HDAC5. Increases in [Na(+)](i)
      activate SIK1 and MEF2 via a parallel increase in intracellular calcium through
      the reverse mode of Na(+)/Ca(2+)-exchanger and activation of CaMK1. These data
      obtained in a cardiac cell line suggest that increases in intracellular sodium
      could influence myocardial growth by controlling transcriptional activation and
      gene expression throughout the activation of the SIK1 network.

PMID- 22467311
TI  - Functional role of astrocyte glutamate receptors and carbon monoxide in cerebral
      vasodilation response to glutamate.
AB  - In newborn pigs, vasodilation of pial arterioles in response to glutamate is
      mediated via carbon monoxide (CO), a gaseous messenger endogenously produced from
      heme degradation by a heme oxygenase (HO)-catalyzed reaction. We addressed the
      hypothesis that ionotropic glutamate receptors (iGluRs), including N-methyl-D
      aspartic acid (NMDA)- and 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic
      acid (AMPA)/kainate-type receptors, expressed in cortical astrocytes mediate
      glutamate-induced astrocyte HO activation that leads to cerebral vasodilation.
      Acute vasoactive effects of topical iGluR agonists were determined by intravital
      microscopy using closed cranial windows in anesthetized newborn pigs. iGluR
      agonists, including NMDA, (+/-)1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis
      ACPD), AMPA, and kainate, produced pial arteriolar dilation. Topical L-2
      aminoadipic acid, a gliotoxin that selectively disrupts glia limitans, reduced
      vasodilation caused by iGluR agonists, but not by hypercapnia, bradykinin, or
      sodium nitroprusside. In freshly isolated and cultured cortical astrocytes
      constitutively expressing HO-2, iGluR agonists NMDA, cis-ACPD, AMPA, and kainate
      rapidly increased CO production two- to threefold. Astrocytes overexpressing
      inducible HO-1 had high baseline CO but were less sensitive to glutamate
      stimulation of CO production when compared with HO-2-expressing astrocytes.
      Glutamate-induced astrocyte HO-2-mediated CO production was inhibited by either
      the NMDA receptor antagonist (R)-3C4HPG or the AMPA/kainate receptor antagonist
      DNQX. Accordingly, either antagonist abolished pial arteriolar dilation in
      response to glutamate, NMDA, and AMPA, indicating functional interaction among
      various subtypes of astrocytic iGluRs in response to glutamate stimulation.
      Overall, these data indicate that the astrocyte component of the neurovascular
      unit is responsible for the vasodilation response of pial arterioles to topically
      applied glutamate via iGluRs that are functionally linked to activation of
      constitutive HO in newborn piglets.

PMID- 22467313
TI  - Frequency-dependent left ventricular performance in women and men.
AB  - We aimed to determine whether sex differences in humans extend to the dynamic
      response of the left ventricular (LV) chamber to changes in heart rate (HR).
      Several observations suggest sex influences LV structure and function in health;
      moreover, this physiology is also affected in a sex-specific manner by aging.
      Eight postmenopausal women and eight similarly aged men underwent a cardiac
      catheterization-based study for force-interval relationships of the LV. HR was
      controlled by right atrial (RA) pacing, and LV +dP/dt(max) and volume were
      assessed by micromanometer-tipped catheter and Doppler echocardiography,
      respectively. Analysis of approximated LV pressure-volume relationships was
      performed using a time-varying model of elastance. External stroke work was also
      calculated. The relationship between HR and LV +dP/dt(max) was expressed as LV
      +dP/dt(max) = b + mHR. The slope (m) of the relationship was steeper in women
      compared with men (11.8 +/- 4.0 vs. 6.1 +/- 4.1 mmHg.s(-1).beats(-1).min(-1), P =
      0.01). The greater increase in contractility in women was reproducibly observed
      after normalizing LV +dP/dt(max) to LV end-diastolic volume (LVVed) or by
      measuring end-systolic elastance. LVVed and stroke volume decreased more in
      women. Thus, despite greater increases in contractility, HR was associated with a
      lesser rise in cardiac output and a steeper fall in external stroke work in
      women. Compared with men, women exhibit greater inotropic responses to
      incremental RA pacing, which occurs at the same time as a steeper decline in
      external stroke work. In older adults, we observed sexual dimorphism in
      determinants of LV mechanical performance.

PMID- 22467312
TI  - Endothelium-specific sepiapterin reductase deficiency in DOCA-salt hypertension.
AB  - The endothelial nitric oxide synthase (eNOS) requires tetrahydrobiopterin (H(4)B)
      as a cofactor and, in its absence, produces superoxide (O(2)(.-)) rather than
      nitric oxide (NO(.)), a condition referred to as eNOS uncoupling. DOCA-salt
      induced hypertension is associated with H(4)B oxidation and uncoupling of eNOS.
      The present study investigated whether administration of sepiapterin or H(4)B
      recouples eNOS in DOCA-salt hypertension. Bioavailable NO(.) detected by electron
      spin resonance was markedly reduced in aortas of DOCA-salt hypertensive mice.
      Preincubation with sepiapterin (10 MUmol/l for 30 min) failed to improve NO(.)
      bioavailability in hypertensive aortas while it augmented NO(.) production from
      control vessels, implicating a hypertension-associated deficiency in sepiapterin
      reductase (SPR), the rate-limiting enzyme for sepiapterin conversion to H(4)B.
      Indeed, a decreased SPR expression was observed in aortic endothelial cells, but
      not in endothelium-denuded aortic remains, implicating an endothelium-specific
      SPR deficiency. Administration of hypertensive aortas with H(4)B (10 MUmol/l, 30
      min) partially restored vascular NO(.) production. Combined administration of
      H(4)B and the NADPH oxidase inhibitor apocynin (100 MUmol/l, 30 min) fully
      restored NO(.) bioavailability while reducing O(2)(.-) production. In angiotensin
      II-induced hypertension, however, aortic endothelial SPR expression was not
      affected. In summary, administration of sepiapterin is not effective in
      recoupling eNOS in DOCA-salt hypertension, due to an endothelium-specific loss in
      SPR, whereas coadministration of H(4)B and apocynin is highly efficient in
      recoupling eNOS. This is consistent with our previous observations that in
      angiotensin II hypertension, endothelial deficiency in dihydrofolate reductase is
      alternatively responsible for uncoupling of eNOS. Taken together, these data
      indicate that strategies specifically targeting at different H(4)B metabolic
      enzymes might be necessary in restoring eNOS function in different types of
      hypertension.

PMID- 22467314
TI  - Signal feature extraction by multi-scale PCA and its application to respiratory
      sound classification.
AB  - Respiratory sound (RS) signals carry significant information about the underlying
      functioning of the pulmonary system by the presence of adventitious sounds.
      Although many studies have addressed the problem of pathological RS
      classification, only a limited number of scientific works have focused in multi
      scale analysis. This paper proposes a new signal classification scheme for
      various types of RS based on multi-scale principal component analysis as a signal
      enhancement and feature extraction method to capture major variability of Fourier
      power spectra of the signal. Since we classify RS signals in a high dimensional
      feature subspace, a new classification method, called empirical classification,
      is developed for further signal dimension reduction in the classification step
      and has been shown to be more robust and outperform other simple classifiers. An
      overall accuracy of 98.34% for the classification of 689 real RS recording
      segments shows the promising performance of the presented method.

PMID- 22467315
TI  - Non-endothelial cell endothelin-B receptors limit neointima formation following
      vascular injury.
AB  - AIMS: The potent vasoconstrictor endothelin-1 (ET-1), acting on the endothelin-A
      (ETA) receptor, promotes intimal lesion formation following vascular injury. The
      endothelin-B (ETB) receptor, which mediates nitric oxide release and ET-1
      clearance in endothelial cells, may moderate lesion formation, but this is less
      clear. We used selective ET receptor antagonists and cell-specific deletion to
      address the hypothesis that ETB receptors in the endothelium inhibit lesion
      formation following arterial injury. METHODS AND RESULTS: Neointimal
      proliferation was induced by wire or ligation injury to the femoral artery in
      mice treated with selective ETA (ABT-627) and/or ETB antagonists (A192621).
      Measurement of lesion formation by optical projection tomography and histology
      indicated that ETA blockade reduced lesion burden in both models. Although ETB
      blockade had little effect on ligation injury-induced lesion formation, after
      wire injury, blockade of the ETB receptor increased lesion burden (184% of
      vehicle; P < 0.05) and reversed the protective effects of an ETA antagonist.
      Selective deletion of ETB receptors from the endothelium, however, had no effect
      on neointimal lesion size. CONCLUSION: These results are consistent with ETB
      receptor activation playing an important role in limiting neointimal lesion
      formation following acute vascular injury, but indicate that this protective
      effect is not mediated by those ETB receptors expressed by endothelial cells.
      These data support the proposal that selective ETA antagonists may be preferable
      to mixed ETA/ETB antagonists for targeting the arterial response to injury.

PMID- 22467316
TI  - The vascular smooth muscle cell in arterial pathology: a cell that can take on
      multiple roles.
AB  - Vascular smooth muscle cells (VSMCs) are the stromal cells of the vascular wall,
      continually exposed to mechanical signals and biochemical components generated in
      the blood compartment. They are involved in all the physiological functions and
      the pathological changes taking place in the vascular wall. Owing to their
      contractile tonus, VSMCs of resistance vessels participate in the regulation of
      blood pressure and also in hypertension. VSMCs of conduit arteries respond to
      hypertension-induced increases in wall stress by an increase in cell protein
      synthesis (hypertrophy) and extracellular matrix secretion. These responses are
      mediated by complex signalling pathways, mainly involving RhoA and extracellular
      signal-regulated kinase1/2. Serum response factor and miRNA expression represent
      main mechanisms controlling the pattern of gene expression. Ageing also induces
      VSMC phenotypic modulation that could have influence on cell senescence and loss
      of plasticity and reprogramming. In the early stages of human atheroma, VSMCs
      support the lipid overload. Endocytosis/phagocytosis of modified low-density
      lipoproteins, free cholesterol, microvesicles, and apoptotic cells by VSMCs plays
      a major role in the progression of atheroma. Migration and proliferation of VSMCs
      in the intima also participate in plaque progression. The medial VSMC is the
      organizer of the inwardly directed angiogenic response arising from the
      adventitia by overexpressing vascular endothelial growth factor in response to
      lipid-stimulated peroxisome proliferator-activated receptor-gamma, and probably
      also the organizer of the adventitial immune response by secreting chemokines.
      VSMCs are also involved in the response to proteolytic injury via their ability
      to activate blood-borne proteases, to secrete antiproteases, and to clear
      protease/antiprotease complexes.

PMID- 22467317
TI  - Reference intervals and factors contributing to serum cystatin C levels in a
      Chinese population.
AB  - BACKGROUND: Serum cystatin C (Cys-C), an inhibitor of cysteine proteases, has
      been suggested as an ideal biomarker of glomerular filtration rate (GFR).
      OBJECTIVES: The objective of this study was to describe the reference intervals
      of serum Cys-C and identify factors associated with serum Cys-C or its
      variability, including age, gender, creatinine (Crea), blood urea nitrogen (BUN),
      and uric acid (UA). DESIGN AND METHODS: Serum Cys-C, Crea, BUN, and UA were
      measured in 4,517 healthy participants aged 8-89 years attending our hospital.
      Serum Cys-C was analyzed using a latex-enhanced immunoturbidimetric method. Crea
      were tested by picric acid jaffe method, BUN, and UA by kinetic UV assays.
      RESULTS: The predominant characteristic of Cys-C distribution was that Cys-C
      concentration in age >=60 years group was the highest (P < 0.05). The differences
      of Cys-C concentration between males and females existed for subjects aged from
      30 to 59 years (P < 0.05). In a multiple model adjusted only for gender and age,
      gender (beta = 0.007) has stronger effect on Cys-C levels, compared with age
      (beta = 0.003). The clinical variables, comprised of age, gender, Crea, BUN, and
      UA, involved in the fully adjusted equation accounted for 37.6% of variation of
      Cys-C. CONCLUSIONS: Ninety-five percent reference intervals for healthy
      population were partitioned into three categories only by age, 0.59-1.07 mg/L for
      subjects aged 19-59 years; 0.74-1.14 mg/L for the older aged >=60 years; and 0.63
      1.11 mg/L for children aged <=18 years. Serum Cys-C is significantly related to
      gender, age, UA, Crea, and BUN. Besides, there are still other factors
      contributing to variation of Cys-C levels.

PMID- 22467318
TI  - Bone turnover markers failed to predict the occurrence of osteonecrosis of the
      femoral head: a preliminary study.
AB  - BACKGROUND: The early detection of osteonecrosis of the femoral head (ONFH) is
      difficult, but important for prevention of destruction of the femoral head. The
      objective of this study was to determine whether the occurrence of osteonecrosis
      of the femoral head (ONFH) correlates with changes in bone turnover markers.
      METHODS: In 40 patients undergoing primary total hip arthroplasty (THA),
      different bone turnover markers and hormones (bone specific alkaline phosphatase,
      osteocalcin, beta cross-laps, 25-hydroxy-cholecalciferol, and parathormone)
      gained from blood were determined on the morning of the surgery. Twenty-two
      patients needed a THA due to progressed ONFH. In 18 cases blood was gained from
      patients with the indication for a THA given due to advanced osteoarthritis (AO)
      of the hip. RESULTS: Bone specific alkaline phosphatase, osteocalcin, beta cross
      laps, and parathormone did not show any deviation from standard values, neither
      for the group of osteonecrosis nor for the osteoarthritis group. 25-Hydroxy
      cholecalciferol revealed on average decreased values without significant
      differences between both groups (P < 0.05). The tested bone turnover markers and
      hormones failed to predict the occurrence of ONFH. Thus, the focus has to be put
      on different parameters to find a specific parameter that possibly predicts the
      risk of ostenecrosis and that is suited to follow up ONFH.

PMID- 22467319
TI  - Urine and serum cathepsin B concentrations in the transitional cell carcinoma of
      the bladder.
AB  - BACKGROUND: It has been shown that expression and activity of lysosomal
      proteolytic enzymes (i.e., cathepsin B) correlate with tumor progression in
      various neoplasms. We investigate possible correlation of cathepsin B
      concentrations with grading and invasivity of tumorous bladder tissue. METHOD:
      Cathepsin B concentrations in serum and urine were measured in 40 patients (29
      men, 11 women, mean age 68 years) with transitional cell carcinoma (TCC) of the
      bladder without metastases and in control group of 64 healthy subjects (28 men,
      36 women, mean age 55 years) using commercially available enzymatic immunoassay.
      Concentration of cathepsin B in urine was adjusted on creatinine. Urinary
      creatinine in all samples was measured by enzymatic creatinase method. Patients
      were divided into groups according to the grading (low grading: 18 patients, high
      grading: 22 patients) and invasivity of the carcinoma (nonmuscle-invasive tumors:
      23 patients, invasive tumors: 17 patients). RESULT: Concentrations of cathepsin B
      in urine were significantly elevated in patients than in control group (Median =
      3.87 MUg/L vs. 1.35 MUg/L, P = 0.0002). Similarly, the ratio of U-cathepsin
      B/creatinine was significantly higher in patients (Median: 0.44 MUg/mmol
      creatinine vs. 0.17 MUg/mmol creatinine, P < 0.0001). U-cathepsin B may prove to
      be useful biomarker (area under the curve [AUC] = 0.72 and 0.73 for the U
      cathepsin B/creatinine ratio, respectively). S-cathepsin B significantly
      correlated with grading of carcinoma (P = 0.02) and U-cathepsin B and U-cathepsin
      B/creatinine are positively associated with invasive tumors (P = 0.0001 and P =
      0.002). CONCLUSION: Cathepsin B concentrations correlate well with grading and
      invasivity of tumors and may have diagnostic value in investigation of bladder
      cell carcinoma. New index U-cathepsin B/Creatinine ratio is more appropriate
      biomarker to monitor TCC, than U-cathepsin B so far.

PMID- 22467320
TI  - Effect of pneumatic tube delivery system rate and distance on hemolysis of blood
      specimens.
AB  - BACKGROUND: We evaluated the effects of pneumatic tube system (PTS) transport
      rates and distances on routine hematology and coagulation analysis. PTS effects
      on centrifuged blood samples were also examined. METHOD: The study was completed
      at Dicle University Hospital, which has the longest pneumatic tube system in
      Turkey. Blood samples were collected at three different locations within the
      hospital and an emergency department, and delivered to the central laboratory by
      the PTS or a human carrier. Samples were transported at different rates and over
      varying distances. Each specimen's potassium (K) and lactic dehydrogenase (LDH)
      levels, in both the serum and plasma, were tracked to monitor hemolysis.
      Measurements of LDH and K were obtained using heparin or citrate. RESULT: A
      positive correlation was observed between distance and hemolysis in serum samples
      transported at 4.2 m/sec, and at 3.1 m/sec for more than 2200 m (r = 0.774 and r
      = 0.766, respectively). Distance and hemolysis were also correlated in non
      centrifuged samples (r = 0.871). The alterations in plasma LDH and K levels at
      different rates and PTS lengths were not statistically significant. CONCLUSION:
      The rate of hemolysis in PTS transported samples, dependent on PTS length and
      rate, may seriously affect routine tests of non-centrifuged samples.

PMID- 22467321
TI  - Evaluation of the new test VERSANT CT/GC DNA 1.0 assay for the detection of
      Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens.
AB  - Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the two most common
      sexually transmitted bacterial infections in developed countries. The purpose of
      the present study was evaluating a new system for CT/GC detection in urine
      specimens. A total of 700 urine specimens were obtained from patients attending
      the STD Outpatients Clinic of St. Orsola University Hospital, Bologna, Italy.
      Samples were tested by VERSANT(r) CT/GC DNA 1.0 Assay (Siemens Healthcare
      Diagnostics Inc., Tarrytown, NY), a multiplex Real-Time PCR assay, for
      simultaneous CT/GC detection. Results obtained by VERSANT assay were compared
      with those obtained by culturing genital secretions of the same patients.
      Moreover, urine specimens testing positive in VERSANT assay were retested by in
      house PCR assays, used as confirmatory tests. VERSANT(r) CT/GC DNA 1.0 Assay
      performed with 99.4% and 99.2% of specificity for GC and CT detection,
      respectively, whereas sensitivity was 100% both for CT and GC. Culture methods
      were 100% specific, but far less sensitive than VERSANT assay. VERSANT(r) CT/GC
      DNA 1.0 Assay demonstrated to be a highly sensitive and specific technique for
      CT/GC detection.

PMID- 22467322
TI  - Comparative evaluation of serum C-reactive protein (CRP) levels in the different
      histological subtypes of esophageal cancer (squamous cell carcinoma and
      adenocarcinoma of esophagus).
AB  - Elevated C-reactive protein (CRP) levels have been found in patients with several
      malignancies. The aim of the present study was to analyze the diagnostic and
      prognostic values of CRP levels measurement in esophageal cancer (EC) patients in
      relation to its different histological subtypes (squamous cell carcinoma-ESCC and
      adenocarcinoma-AC of esophagus) and compared them with classic tumor markers
      carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag). The
      diagnostic sensitivity, specificity, and the areas under receiver operating
      characteristic curves (AUC) for all the proteins tested were defined. Serum CRP
      levels were statistically higher in EC, ESCC, and AC patients compared to healthy
      subjects and significantly increased in EC and ESCC patients with the presence of
      lymph node and distant metastases. The percentage of elevated CRP results in all
      the analyzed subgroups (EC, ESCC, and AC) was higher than CEA and SCC-Ag,
      similarly as AUC for CRP in comparison to SCC-Ag. Serum CRP level was a
      significant predictor of EC and ESCC patients' survival in univariate analysis.
      In conclusion, these results indicate that CRP can be used as an adjunct in
      evaluating the tumor markers-CEA and SCC-Ag and may improve the clinical
      diagnosis and follow-up of EC patients, especially for ESCC subgroup.

PMID- 22467323
TI  - Albuminuria, proteinuria, and urinary albumin to protein ratio in chronic kidney
      disease.
AB  - BACKGROUND: Both albuminuria and proteinuria are important disease markers of
      chronic kidney disease (CKD). Their relationship and the ratio between urinary
      albumin and protein in patients with CKD have not been investigated. Whether
      clinical features can affect these measurements is not clear. METHODS: We
      conducted a cross-sectional study in 602 CKD patients. Demographic data,
      including age, gender, and co-morbidity such as diabetes, hypertension,
      hyperuricemia, and hyperlipidemia, were reviewed and recorded. Their urinary
      albumin, total protein, and creatinine were determined and urinary albumin to
      creatinine ratio (UACR), total protein to creatinine ratio (UPCR), and albumin to
      total protein ratio (UAPR) were calculated. Their estimated glomerular filtration
      rate (eGFR) was calculated according to serum creatinine. The correlation between
      UACR and UPCR was thus analyzed. We also investigated factors associated with
      these urinary measurements. RESULTS: UACR and UPCR increased progressively as
      renal function deteriorated, while UAPR increased to a plateau in CKD stage 4.
      There was direct relationship between UACR and UPCR. UAPR rose exponentially with
      the increase of both UACR and UPCR when UACR <500 mg/g or UPCR <1,000 mg/g.
      Multivariate regression analysis revealed diabetes and hyperuricemia were
      associated with increased UACR and UPCR, while both urinary parameters were
      inversely related to male gender and eGFR. Diabetes and hyperuricemia were
      associated with increased UAPR and UAPR was negatively correlated with age and
      eGFR. CONCLUSION: There was a significant association between UACR and UPCR in
      patients with CKD. Characteristics of patients, renal function, and co
      morbidities all affected UACR, UPCR, and UAPR.

PMID- 22467324
TI  - Expression of urokinase-type plasminogen activator (uPA), its receptor (uPAR),
      and inhibitor (PAI-1) in human breast carcinomas and their clinical relevance.
AB  - Serine proteases convert plasminogen to plasmin which is involved in tissue
      remodeling under physiologic and pathophysiologic conditions, including breast
      carcinoma invasion and progression. Both urokinase-type plasminogen activator
      (uPA) and pro-uPA associate with uPA receptor (uPAR) on target cells, where
      plasminogen activator inhibitors (e.g., PAI-1) may modulate their activities.
      Expression levels of these factors were compared in breast carcinomas relative to
      patient characteristics, carcinoma features, and clinical outcome. uPA, uPAR, and
      PAI-1 were quantified by enzyme-linked immunosorbent assay (ELISA) in extracts of
      226 biopsies while estrogen receptor (ER) and progestin receptor (PR) were
      determined by enzyme immunoassay (EIA) or radio-ligand binding. Each set of
      assays contained a novel reference specimen with known quantities of each of
      these five analytes. Levels in ng/mg protein of these biomarkers exhibited
      ranges: uPA (0-12.3); uPAR (0-19.5); PAI-1 (0-91.2). When considered
      independently, expression of uPA, uPAR, or PAI-1 was unrelated to patient age or
      menopausal status. Although no correlation was observed between each analyte with
      stage, grade, or ER/PR status, levels appeared to differ with pathology and nodal
      status. A dendrogram from hierarchical clustering of uPA, uPAR, and PAI-1 levels
      in 106 specimens revealed three clusters of breast cancer patients. Kaplan-Meier
      analyses of uPA, uPAR, and PAI-1 indicated a correlation with overall survival
      (OS), suggesting collective examination of these biomarkers is useful in
      predicting clinical outcome of breast cancer.

PMID- 22467325
TI  - RHD allelic identification among D-Brazilian blood donors as a routine test using
      pools of DNA.
AB  - BACKGROUND: RHD alleles leading to a reduced expression of D antigen of the red
      blood cell (RBC) surface may be erroneously typed as D- by serology and may cause
      anti-D immunizations when transfused to recipients. METHODS: To determine the
      occurrence of such alleles among apparent D- blood donors, molecular typing was
      implemented as a routine test using a pool of DNA. A total of 2,450 pretyped D-
      samples were tested in pools of 10 for the RHD-specific polymorphism in intron 4
      and exon 7. Samples in polymer chain reaction (PCR) positive pools were
      individually reevaluated by exon-specific PCRs, sequencing, and serologic
      methods. RESULTS: Among 2,450 serologically D- blood donor samples tested, 101
      (4.1%) carried the RHD gene. Nonfunctional RHD (RHDpsi, RHD*CE(2-9)-D, and
      RHD*CE(3-7)-D), different weak D alleles such as RHD*weak D type 1, RHD*weak D
      type 4.3, RHD*weak D type 5, RHD*weak D type 38, and RHD*DEL were identified.
      CONCLUSION: We employed a PCR-based assay for RHD as a routine test using pools
      of ten DNA blood donor samples. The integration of RHD genotyping into the
      routine screening program using pools of DNA samples was straightforward. As a
      consequence, 19 (0.8%) blood donors carrying a weak D and Del phenotypes with the
      potential of causing anti-D immunizations in recipients were reclassified as D+.
      For each population, it would be necessary to adapt the RHD genotyping strategy
      to the spectrum of prevalent alleles.

PMID- 22467326
TI  - Imbalance of circulating T-lymphocyte subpopulation in COPD and its relationship
      with CAT performance.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with systemic effects,
      and T-cell-mediated immunity was involved in the COPD. COPD Assessment Test (CAT)
      could provide a valid, reliable, and standardized measure of COPD health status.
      The objective of this study was determination of lymphocyte subpopulation in
      patients with stable COPD (n = 52) and to ascertain if a relationship existed
      between T-lymphocyte subpopulation and CAT performance. The stable COPD patients
      were assessed with CAT, and divided into four groups with score >30 (n = 8), 20<
      score <=30 (n = 16), 10< score <=20 (n = 20), and score <=10 (n = 8). Spearman's
      rank correlation was used to determine the relationship between proportion of T
      lymphocyte and CAT score. We found an elevated proportion of CD8(+)  cells in
      COPD patients of the group with score >30 compared to other groups. Proportion of
      CD4(+)  cells was significantly lower in the groups with score >30 and 20< score
      <=30 when compared to groups with 10< score <=20 and score <=10. The CD4(+)
      :CD8(+)  ratio was also significantly lower in the groups with score >30 and 20<
      score <=30. Of note are the correlations of proportion of CD8(+)  cells and
      CD4(+) :CD8(+)  ratio with CAT performance when score >20. No correlations
      existed between proportion of CD4(+) , CD8(+)  cells, CD4(+) :CD8(+)  ratio, and
      CAT performance when score <=20. Our results show that the determinants of T
      lymphocyte subpopulation in COPD patients were value to assess physical
      conditions. We considered CD4(+)  and CD8(+)  T lymphocytes to be a
      representative and stable parameter in grading of health status in COPD patients.

PMID- 22467327
TI  - Visfatin levels in nonalcoholic fatty liver disease.
AB  - PURPOSE: Recently, role of adipokin in the pathogenesis of nonalcoholic fatty
      liver disease (NAFLD) has been suggested. Among adipokins, role of leptin and
      adiponectin is rather well known; however, there are only a few data concerning
      visfatin. MATERIAL AND METHODS: NAFLD is confirmed in 30 patients by
      ultrasonography. As a control group, patients without fatty liver or other liver
      diseases were included. Viral hepatitis, metabolic liver diseases, and autoimmune
      hepatitis and consumption of alcohol were excluded in all patients. Fasting serum
      level of visfatin was determined by ELISA method. RESULTS: Serum visfatin
      concentration in the NAFLD group (14.7 +/- 8.1 ng/ml) was significantly higher
      than in controls (9.4 +/- 1.6 ng/ml) (P < 0.001). There were no correlations
      between visfatin and anthropometric parameters, transaminases, lipids, and
      homeostasis model assessment-estimated insulin resistance (HOMA-IR). CONCLUSION:
      Serum visfatin concentration increases in patients with NAFLD.

PMID- 22467328
TI  - Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as
      risk factors for cardiovascular disease.
AB  - PURPOSE: Elevation of homocysteine levels have been involved as a remarkable risk
      factor for cardiovascular disease. Decreased bioavailability of nitric oxide (NO)
      may result in abnormal reactions between the vessel wall and platelets and is
      thus involved in the initiation and progression of atherosclerosis. We aimed to
      assess the effect of a low dose oral contraceptive pills on homocysteine and NO
      levels which may influence the individual cardiovascular risk by regulation of
      endothelial function and development of atherosclerosis. METHODS: The study was
      conducted in 50 healthy women with normal menstrual cycles as control group and
      50 healthy women receiving oral contraceptive pill for at least three menstrual
      cycles. Homocysteine concentration was assayed by an enzyme immunoassay method
      and a colorimetric assay was used for determination of NO levels. RESULTS: After
      3 months of treatment, homocysteine levels were significantly increased (P =
      0.027), and there was a significant and considerable decrease (P = 0.048) in NO
      concentration of oral contraceptive pill (OCP) consumers. CONCLUSIONS: Our data
      indicates that OCPs increase the homocysteine (HCY) and reduce the NO levels.
      These findings warrant a possible implication of OCP in change of risk of
      development of coronary heart disease.

PMID- 22467329
TI  - Variability of a closed, rebreathing setup for multiple breath wash-out testing
      in children.
AB  - OBJECTIVE: The multiple breath wash-out technique (MBW) that measures lung
      clearance index (LCI) and functional residual capacity (FRC) may be more
      sensitive than spirometry for identification of early obstructive airways
      disease. The open MBW setup using mass spectrometry referenced in previous
      publications is not readily available in the U.S. Our objective was to assess
      validity and sensitivity of a commercially available device that uses a closed
      (rebreathing) setup with photoacoustic spectroscopy for MBW testing. STUDY DESIGN
      AND METHODS: Subjects aged 5-21 who were either healthy or had a history of
      cystic fibrosis were enrolled. Subjects completed MBW (Innocor device;
      Innovision, Denmark) and spirometry; measures obtained included LCI, FRC, and
      forced expiratory volume in 1 sec, as well as changes in end-tidal carbon dioxide
      levels (CO(2) ) and tidal volume during MBW testing. RESULTS: Seventeen subjects
      attempted a total of 76 MBW maneuvers; 80% were completed and 60% met criteria
      for acceptability; most were unacceptable due to errors in the tracer gas curve.
      Substantial intra-subject variability for LCI and FRC were noted (mean 26% +/- 55
      and 36% +/- 63, respectively). Subjects were also noted to have significant
      increases in exhaled CO(2) and tidal volume during MBW testing. CONCLUSIONS: In
      our initial experience using a commercially available closed setup for MBW
      testing, we found a significant degree of intra-subject variability leading us to
      suspend testing. Variability could be due to hypercapnea and instability of tidal
      breathing secondary to the rebreathing setup. Further studies are needed to
      better understand the closed system MBW setup.

PMID- 22467330
TI  - Increasing capacity for environmental engineering in Salta, Argentina.
AB  - BACKGROUND: The Fogarty International Center (FIC) of the United States National
      Institutes of Health includes the International Training and Research in
      Environmental and Occupational Health (ITREOH) Program. The "International
      Training Program in Environmental Toxicology and Public Health" Center, funded in
      2002 is based at the University of California, Davis, and is part of the ITREOH
      group of Centers. It has major efforts focused at the public universities in
      Montevideo, Uruguay, and Salta, Argentina. RESULTS: Training and research efforts
      in Salta begun in 2005 in the College of Engineering. A donated used real-time
      PCR machine was the starting point and the initial FIC support was instrumental
      to face other problems including physical space, research projects and grants,
      trainees, training, networking, and distractions/opportunities in order to
      develop local capacities in Environmental Engineering using modern methodology.
      After 6 years of successful work, the Salta center has become a reference Center
      in the field, and is still growing and consolidating. CONCLUSIONS: This program
      has had a significant impact locally and regionally. The model used in Argentina
      could be easily adapted to other fields or types of projects in Argentina and in
      other developing countries.

PMID- 22467331
TI  - Kinetic modeling of the photosynthetic growth of Chlamydomonas reinhardtii in a
      photobioreactor.
AB  - The aim of this study was to establish and validate a model for the
      photosynthetic growth of Chlamydomonas reinhardtii in photobioreactors (PBRs).
      The proposed model is based on an energetic analysis of the excitation energy
      transfer in the photosynthesis apparatus (the Z-scheme for photosynthesis). This
      approach has already been validated in cyanobacteria (Arthorspira platensis) and
      is extended here to predict the volumetric biomass productivity for the microalga
      C. reinhardtii in autotrophic conditions, taking into consideration the two
      metabolic processes taking place in this eukaryotic microorganism, namely
      photosynthesis and respiration. The kinetic growth model obtained was then
      coupled to a radiative transfer model (the two-flux model) to determine the local
      kinetics, and thereby the volumetric biomass productivity, in a torus PBR. The
      model was found to predict PBR performances accurately for a broad set of
      operating conditions, including both light-limited and kinetic growth regimes,
      with a variance of less than 10% between experimental results and simulations.

PMID- 22467332
TI  - Mice lacking epidermal PPARgamma exhibit a marked augmentation in
      photocarcinogenesis associated with increased UVB-induced apoptosis, inflammation
      and barrier dysfunction.
AB  - Recent studies suggest that peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists may have cancer chemopreventive activity. Other studies have
      shown that loss of epidermal PPARgamma results in enhanced chemical
      carcinogenesis in mice via unknown mechanisms. However, ultraviolet B (UVB)
      exposure represents the primary etiological agent for skin cancer formation and
      the role of PPARgamma in photobiology and photocarcinogenesis is unknown. In
      previous studies, we demonstrated that UVB irradiation of cells results in the
      formation of oxidized glycerophosphocholines that exhibit PPARgamma ligand
      activity. We therefore hypothesized that PPARgamma would prove to be a
      chemopreventive target in photocarcinogenesis. We first showed that UVB
      irradiation of mouse skin causes generation of PPARgamma agonist species in vivo.
      We then generated SKH-1 hairless, albino mice deficient in epidermal Pparg (Pparg
      /-(epi)) using a cytokeratin 14 driven Cre-LoxP strategy. Using a chronic model
      of UVB photocarcinogenesis, we next showed that Pparg-/-(epi) mice exhibit an
      earlier onset of tumor formation, increased tumor burden and tumor progression.
      Increased tumor burden in Pparg-/-(epi) mice was accompanied by a significant
      increase in epidermal hyperplasia and p53 positive epidermal cells in surrounding
      skin lacking tumors. After acute UVB irradiation, Pparg-/-(epi) mice exhibited an
      augmentation of both UVB-induced Caspase 3/7 activity and inflammation. Increased
      apoptosis and inflammation was also observed after treatment with the PPARgamma
      antagonist GW9662. With chronic UVB irradiation, Pparg-/-(epi) mice exhibited a
      sustained increase in erythema and transepidermal water loss relative to wildtype
      littermates. This suggests that PPARgamma agonists could have possible
      chemopreventive activity in non-melanoma skin cancer.

PMID- 22467333
TI  - Copper-catalyzed trifluoromethylation of allylsilanes.

PMID- 22467334
TI  - Chronic myeloid leukemia stem cell biology.
AB  - Leukemia progression and relapse is fueled by leukemia stem cells (LSC) that are
      resistant to current treatments. In the progression of chronic myeloid leukemia
      (CML), blast crisis progenitors are capable of adopting more primitive but
      deregulated stem cell features with acquired resistance to targeted therapies.
      This in turn promotes LSC behavior characterized by aberrant self-renewal,
      differentiation, and survival capacity. Multiple reports suggest that cell cycle
      alterations, activation of critical signaling pathways, aberrant
      microenvironmental cues from the hematopoietic niche, and aberrant epigenetic
      events and deregulation of RNA processing may facilitate the enhanced survival
      and malignant transformation of CML progenitors. Here we review the molecular
      evolution of CML LSC that promotes CML progression and relapse. Recent advances
      in these areas have identified novel targets that represent important avenues for
      future therapeutic approaches aimed at selectively eradicating the LSC population
      while sparing normal hematopoietic progenitors in patients suffering from chronic
      myeloid malignancies.

PMID- 22467335
TI  - Surface plasmon resonance based biosensor technique: a review.
AB  - Optical Surface plasmon resonance (SPR) biosensors represent the most advanced
      and developed optical label-free biosensor technology. Optical SPR biosensors are
      a powerful detection and analysis tool that has vast applications in
      environmental protection, biotechnology, medical diagnostics, drug screening,
      food safety and security. This article reviews the recent development of SPR
      biosensor techniques, including bulk SPR and localized SPR (LSPR) biosensors, for
      detecting interactions between an analyte of interest in solution and a
      biomolecular recognition. The concepts of bulk and localized SPs and the working
      principles of both sensing techniques are introduced. Major sensing advances on
      biorecognition elements, measurement formats, and sensing platforms are
      presented. Finally, the discussions on both biosensor techniques as well as
      comparison of both SPR sensing techniques are made.

PMID- 22467336
TI  - Tissue distribution studies of protein therapeutics using molecular probes:
      molecular imaging.
AB  - Molecular imaging techniques for protein therapeutics rely on reporter labels,
      especially radionuclides or sometimes near-infrared fluorescent moieties, which
      must be introduced with minimal perturbation of the protein's function in vivo
      and are detected non-invasively during whole-body imaging. PET is the most
      sensitive whole-body imaging technique available, making it possible to perform
      biodistribution studies in humans with as little as 1 mg of injected antibody
      carrying 1 mCi (37 MBq) of zirconium-89 radiolabel. Different labeling
      chemistries facilitate a variety of optical and radionuclide methods that offer
      complementary information from microscopy and autoradiography and offer some
      trade-offs in whole-body imaging between cost and logistic difficulty and image
      quality and sensitivity (how much protein needs to be injected). Interpretation
      of tissue uptake requires consideration of label that has been catabolized and
      possibly residualized. Image contrast depends as much on background signal as it
      does on tissue uptake, and so the choice of injected dose and scan timing guides
      the selection of a suitable label and helps to optimize image quality. Although
      only recently developed, zirconium-89 PET techniques allow for the most
      quantitative tomographic imaging at millimeter resolution in small animals and
      they translate very well into clinical use as exemplified by studies of
      radiolabeled antibodies, including trastuzumab in breast cancer patients, in The
      Netherlands.

PMID- 22467337
TI  - New neurons generated from running are broadly recruited into neuronal activation
      associated with three different hippocampus-involved tasks.
AB  - Running increases the formation of new neurons in the adult rodent hippocampus.
      However, the function of new neurons generated from running is currently unknown.
      One hypothesis is that new neurons from running contribute to enhanced cognitive
      function by increasing plasticity in the adult hippocampus. An alternative
      hypothesis is that new neurons generated from running incorporate into experience
      specific hippocampal networks that only become active during running. The purpose
      of this experiment was to determine if new neurons generated from running are
      selectively activated by running, or can become recruited into granule cell
      activity occurring during performance on other behavioral tasks that engage the
      hippocampus. Therefore, the activation of new 5-6 week neurons was detected using
      BrdU, NeuN, and Zif268 triple-label immunohistochemistry in cohorts of female
      running and sedentary adult C57BL/6J mice following participation in one of three
      different tasks: the Morris water maze, novel environment exploration, or wheel
      running. Results showed that running and sedentary mice displayed a nearly
      equivalent proportion of new neurons that expressed Zif268 following each task.
      Since running approximately doubled the number of new neurons, the results
      demonstrated that running mice had a greater number of new neurons recruited into
      the Zif268 induction in the granule cell layer following each task than sedentary
      mice. The results suggest that new neurons incorporated into hippocampal
      circuitry from running are not just activated by wheel running itself, but rather
      become broadly recruited into granule cell layer activity during distinct
      behavioral experiences.

PMID- 22467338
TI  - Effects of alkali metal ion cationization on fragmentation pathways of triazole
      epothilone.
AB  - The collisionally activated dissociation mass spectra of the protonated and
      alkali metal cationized ions of a triazole-epothilone analogue were studied in a
      Fourier transform ion cyclotron resonance mass spectrometer. The fragmentation
      pathway of the protonated ion was characterized by the loss of the unit of
      C(3)H(4)O(3). However, another fragmentation pathway with the loss of
      C(3)H(2)O(2) was identified for the complex ions with Na(+), K(+), Rb(+), and
      Cs(+). The branching ratio of the second pathway increases with the increment of
      the size of alkali metal ions. Theoretical calculations based on density
      functional theory (DFT) method show the difference in the binding position of the
      proton and the metal ions. With the increase of the radii of the metal ions,
      progressive changes in the macrocycle of the compound are induced, which cause
      the corresponding change in their fragmentation pathways. It has also been found
      that the interaction energy between the compound and the metal ion decreases with
      increase in the size of the latter. This is consistent with the experimental
      results, which show that cesiated complexes readily eject Cs(+) when subject to
      collisions.

PMID- 22467339
TI  - PEPPSI-type palladium complexes containing basic 1,2,3-triazolylidene ligands and
      their role in Suzuki-Miyaura catalysis.
AB  - A series of PEPPSI-type palladium(II) complexes was synthesized that contain 3
      chloropyridine as an easily removable ligand and a triazolylidene as a strongly
      donating mesoionic spectator ligand. Catalytic tests in Suzuki-Miyaura cross
      coupling reactions revealed the activity of these complexes towards aryl bromides
      and aryl chlorides at moderate temperatures (50  degrees C). However, the impact
      of steric shielding was the inverse of that observed with related normal
      Nheterocyclic carbenes (imidazol-2-ylidenes) and sterically congested mesityl
      substituents induced lower activity than small alkyl groups. Mechanistic
      investigations, including mercury poisoning experiments, TEM analyses, and ESI
      mass spectrometry, provide evidence for ligand dissociation and the formation of
      nanoparticles as a catalyst resting state. These heterogeneous particles provide
      a reservoir for soluble palladium atoms or clusters as operationally homogeneous
      catalysts for the arylation of aryl halides. Clearly, the substitution of a
      normal N-heterocyclic carbene for a more basic triazolylidene ligand in the
      precatalyst has a profound impact on the mode of action of the catalytic system.

PMID- 22467341
TI  - Managing treatment complexity in cystic fibrosis: challenges and opportunities.
AB  - Cystic fibrosis (CF) is a complex, chronic, multisystem disease for which there
      is currently no cure. Nonetheless, advances in management have led to dramatic
      improvements in patient survival. With this development, new issues have arisen
      for CF patients and their care providers, including an increased symptom burden
      and increased frequency of co-morbidities as patients reach older ages, leading
      to the need for a highly complicated and time-consuming regimen of treatments.
      Such high symptom and treatment burden often leads to non-adherence and low
      levels of competence with administration of therapy, both of which may have
      detrimental impacts on CF outcomes. Optimal management is also hindered by other
      patient-related factors, including inadequacies in disease education which may
      lead to issues with self-management. This is particularly important during the
      transition from parent-directed therapy to independent self-management that
      occurs during adolescence and early adulthood. Clinicians are also faced with a
      considerable challenge when selecting interventions for individual patients;
      although the paradigm of aggressive care necessitates a wide range of therapies,
      there is a limited evidence base with which to compare available therapeutic
      regimens. Novel pharmacological agents are being developed to target the
      underlying cause of CF, while non-pharmacological interventions aim to improve
      competence and maximize adherence and health outcomes. Comparative effectiveness
      research is needed to simplify management and facilitate the implementation of
      appropriate treatment strategies.

PMID- 22467340
TI  - Epigenetic responses following maternal dietary exposure to physiologically
      relevant levels of bisphenol A.
AB  - Animal studies have linked perinatal bisphenol A (BPA) exposure to altered DNA
      methylation, but little attention is given to analyzing multiple physiologically
      relevant doses. Utilizing the viable yellow agouti (A(vy)) mouse, we examine the
      effects of developmental exposure through maternal diet to 50 ng BPA/kg (n = 14
      litters), 50 MUg BPA/kg (n = 9 litters), or 50 mg BPA/kg (n = 13 litters) on
      global and candidate gene methylation at postnatal day 22. Global methylation
      analysis reveals hypermethylation in tail tissue of a/a and A(vy)/a offspring
      across all dose groups compared with controls (n = 11 litters; P < 0.02).
      Analysis of coat color phenotype replicates previous work showing that the
      distribution of 50 mg BPA/kg A(vy)/a offspring shifts toward yellow (P = 0.006)
      by decreasing DNA methylation in the retrotransposon upstream of the Agouti gene
      (P = 0.03). Maternal exposure to 50 MUg or 50 ng BPA/kg, however, results in
      altered coat color distributions in comparison with control (P = 0.04 and 0.02),
      but no DNA methylation effects at the Agouti gene are noted. DNA methylation at
      the CDK5 activator-binding protein (Cabp(IAP)) metastable epiallele shows
      hypermethylation in the 50 MUg BPA/kg offspring, compared with controls (P =
      0.02). Comparison of exposed mouse liver BPA levels to human fetal liver BPA
      levels indicates that the three experimental exposures are physiologically
      relevant. Thus, perinatal BPA exposure affects offspring phenotype and epigenetic
      regulation across multiple doses, indicating the need to evaluate dose effects in
      human clinical and population studies.

PMID- 22467343
TI  - Pre-mRNA splicing and its regulation in Caenorhabditis elegans.
AB  - Alternative splicing is a common mechanism for the generation of multiple
      isoforms of proteins. It can function to expand the proteome of an organism and
      can serve as a way to turn off gene expression after transcription. This review
      focuses on splicing, its regulation and the progress in this field achieved
      through studies in C. elegans. Recent experiments, including RNA-Seq to uncover
      and measure the extent of alternative splicing, comparative genomics to identify
      splicing regulatory elements, and the development of elegant genetic screens
      using fluorescent reporter constructs, have increased our understanding of the
      cis-acting sequences that regulate alternative splicing and the trans-acting
      protein factors that bind to these sequences. The topics covered in this review
      include constitutive splicing factors, identification of alternatively spliced
      genes, alternative splicing regulation and the coupling of alternative splicing
      to nonsense-mediated decay. The significant progress towards uncovering the
      alternative splicing code in this organism is discussed.

PMID- 22467342
TI  - Angiotensin receptor blockers and tumorigenesis: something to be (or not to be)
      concerned about?
AB  - The possibility of carcinogenic side effects of antihypertensive therapies due to
      their chronic administration has been raised multiple times in the past.
      Recently, the issue has again drawn attention, this time in relation to
      angiotensin receptor blockers (ARBs). This, among others, caused both American
      and European drug regulation authorities to review the underlying evidence
      concerning the relationship between this class of medications and potential
      adverse carcinogenic outcome. A plethora of both basic science and preclinical
      evidence has been generated, and three meta-analyses and one nationwide cohort
      have focused on this specific question. The current review aims to summarize the
      contemporary multidisciplinary evidence on whether ARBs may be associated with an
      increased risk of tumorigenesis.

PMID- 22467344
TI  - Do home-visit programs for mothers with infants reduce parenting stress and
      increase social capital in Japan?
AB  - BACKGROUND: Distress during child rearing is known as a risk factor for child
      maltreatment. In addition, it is known that social capital can be a preventive
      factor for child maltreatment. The purpose of this study is to evaluate whether
      the home-visit program reduces parenting stress and increases the social capital
      in the community. METHODS: The home-visit program was implemented when the
      infants were 1-2 month of age (by public health nurses or midwives) and/or 4
      months of age for those mothers who agreed to a home visit by trained community
      staff. Self-administered questionnaires on parenting stress scale and social
      capital were sent to all mothers who delivered a baby between August and November
      2009 in two cities in the Aichi prefecture, Japan. RESULTS: Among 936 mothers,
      347 mothers (follow-up rate: 37%) completed both questionnaires. Scores on
      parenting stress scale scores at 4 months were lower than those at 1-2 months
      among the four groups (no home visit, home visit at 1-2 months, home visit at 4
      months and both). The social trust scores at 4 months were higher than those at 1
      2 months in every group; however, multivariate regression analysis showed that
      there were no differences in the reduction of the parenting stress scale scores
      and increase in social trust between the four groups. CONCLUSION: The home-visit
      program conducted once or twice by public health nurses or trained community
      staff for mothers with infants showed no substantial reduction in maternal stress
      and no increase in social trust.

PMID- 22467345
TI  - Factor structure of self-reported clinical disorders and personality disorders: a
      review of the existing literature and a factor analytical study.
AB  - OBJECTIVES: The aim of this research is to add to the current understanding of
      the latent factor structure of personality disorders by performing a review of
      the existing literature (Study 1) and a factor analytical study on the factor
      structure and the relationship between self-reported Axis I and Axis II
      psychopathology (Study 2). DESIGN: The current research (Study 2) is cross
      sectional and multicenter. RESULTS: We found support for the assumption that the
      borderline personality disorder is a multidimensional construct. Second, we found
      evidence for a single-factor structure of the narcissistic, dependent as well as
      the avoidant personality disorder. Third, we found support for the current
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      distinction between Axis I and Axis II, Axis I psychopathology being explained by
      the factor neuroticism and Axis II disorders to be further subdivided into the
      higher order factors of internalizing and externalizing pathology. CONCLUSIONS:
      An adaptation to the current DSM-IV borderline personality criteria should be
      made, while various findings show that the borderline construct is
      multidimensional. Second, deletion of the dependent and narcissistic personality
      in the DSM-V might be unjust. Third, Axis I psychopathology can be explained by
      the factor neuroticism, and Axis II disorders should be further subdivided into
      the higher order factors of internalizing and externalizing pathology.

PMID- 22467346
TI  - Nickel-promoted tungsten carbide catalysts for cellulose conversion: effect of
      preparation methods.
AB  - A series of Ni-promoted W(2) C catalysts was prepared by means of a post
      impregnation method and evaluated for the catalytic conversion of cellulose into
      ethylene glycol (EG). Quite different from our previously reported Ni-W(2) C/AC
      catalysts, which were prepared by using the co-impregnation method, the
      introduction of Ni by the post-impregnation method did not cause catalyst
      sintering, but resulted in redispersion of the W component, which was identified
      and characterized by means of XRD, TEM, and CO chemisorption. The highly
      dispersed Ni-promoted W(2) C catalyst was very active and selective in cellulose
      conversion into EG, with a 100% conversion of cellulose and a 73.0% yield in EG.
      The underlying reason for the enhanced catalytic performance was most probably
      the significantly higher dispersion of active sites on the catalyst.

PMID- 22467347
TI  - Dissociable anterograde amnesic effects of retrosplenial cortex and hippocampal
      lesions on spontaneous object recognition memory in rats.
AB  - The amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS)
      and hippocampus (HPC) in the spontaneous object recognition (SOR) performance
      were investigated. The SOR test consisted of the sample-exposure session(s) and a
      test session. First, to test retrograde amnesia, rats received four sample
      exposure sessions within a day at 4 weeks and 1 day before the surgery,
      respectively. In the test sessions conducted 1 week after the surgery, both
      lesion groups showed a temporally ungraded retrograde amnesia. Second, to test
      anterograde amnesia, 1- and 4-week retention intervals were inserted between the
      four sample-exposure sessions and the test session. The RS-lesioned rats showed a
      retention interval-dependent impairment in the test sessions, while the HPC
      lesioned rats showed an impairment regardless of the retention interval. Finally,
      to test short-term recognition memory, 5- or 30-min delay was interposed between
      the single sample-exposure session and the test session. Both lesion groups
      performed normally irrespective of the delay length. These results suggest that
      both the RS and HPC are important for long-term object recognition memory, but
      these areas have different roles in it.

PMID- 22467350
TI  - MPH program at Manipal University, India-experiences, challenges, and lessons
      learned.
AB  - BACKGROUND: The UAB-ITREOH program has initiated a skill-based MPH program at
      Manipal University (MU), India, in 2009, to address the critical need for trained
      public health professionals and build institutional public health training
      capacity in the country. METHODS: Funds from Fogarty have supported the
      curriculum development and specialized training of MU faculty to teach in the MPH
      program. RESULTS: The program has been successfully launched and is gaining
      momentum. The lessons learned from our experiences as well as several challenges
      faced from the initialization to execution of the program are described in the
      article. CONCLUSIONS: Government support is crucial for raising the profile of
      this program by accreditation, creating job opportunities and by recognizing
      these professionals as leaders in the public health sector.

PMID- 22467351
TI  - An optimised small-molecule stabiliser of the 14-3-3-PMA2 protein-protein
      interaction.
AB  - Modulation of protein-protein interactions (PPIs) is a highly demanding, but also
      a very promising approach in chemical biology and targeted drug discovery. In
      contrast to inhibiting PPIs with small, chemically tractable molecules,
      stabilisation of these interactions can only be achieved with complex natural
      products, like rapamycin, FK506, taxol, forskolin, brefeldin and fusicoccin.
      Fusicoccin stabilises the activatory complex of the plant H(+)-ATPase PMA2 and 14
      3-3 proteins. Recently, we have shown that the stabilising effect of fusicoccin
      could be mimicked by a trisubstituted pyrrolinone (pyrrolidone1, 1). Here, we
      report the synthesis, functional activity and crystal structure of derivatives of
      1 that stabilise the 14-3-3-PMA2 complex. With a limited compound collection
      three modifications that are important for activity enhancement could be
      determined: 1) conversion of the pyrrolinone scaffold into a pyrazole, 2)
      introduction of a tetrazole moiety to the phenyl ring that contacts PMA2, and 3)
      addition of a bromine to the phenyl ring that exclusively contacts the 14-3-3
      protein. The crystal structure of a pyrazole derivative of 1 in complex with 14-3
      3 and PMA2 revealed that the more rigid core of this molecule positions the
      stabiliser deeper into the rim of the interface, enlarging especially the contact
      surface to PMA2. Combination of the aforementioned features gave rise to a
      molecule (37) that displays a threefold increase in stabilising the 14-3-3-PMA2
      complex over 1. Compound 37 and the other active derivatives show no effect on
      two other important 14-3-3 protein-protein interactions, that is, with CRaf and
      p53. This is the first study that describes the successful optimisation of a PPI
      stabiliser identified by screening.

PMID- 22467353
TI  - A scaled-up system to evaluate zooplankton spatial avoidance and the population
      immediate decline concentration.
AB  - Most laboratory tests may underestimate adverse effects in real scenarios of
      contamination because they imply the forced exposure of organisms to
      contaminants, thus overlooking the possibility of emigration. Avoidance from
      contaminants has been observed in several aquatic organisms, and avoidance-based
      tests have been recommended to be included in risk assessment studies. To reduce
      uncertainty in the extrapolation of laboratory derived results, the first aim of
      the present study was to compare both the median avoidance concentration and the
      lowest-observed-effect gradient (LOEG) values of atrazine for the cladoceran
      Daphnia magna, between an already developed 1.1-m-long system and a scaled-up
      system, three times longer. Second, the present study aimed at evaluating the
      population immediate decline--the proportion of the population that disappears
      (avoids and, if not, dies)--through the integration of the relationships between
      lethality and avoidance versus contaminant concentration. Daphnia magna
      significantly avoided atrazine, during 12-h exposures, with similar results in
      the original and scaled-up systems. The population immediate decline at the 48-h
      median lethal concentration would be 94%. Even at a concentration eliciting only
      5% mortality, the population immediate decline would be over 50%. Achieving a
      higher pertinence of avoidance results and a better understanding of the LOEG
      values and their time dependence, scaling up the system further both spatially
      and temporally, and modeling explicit spatial dynamics in exposure and organism
      movement in space and time are needed.

PMID- 22467354
TI  - Controlling for dilution while manipulating load: perceptual and sensory
      limitations are just two aspects of task difficulty.
AB  - Lavie and de Fockert (2003) proposed that perceptual load and sensory limitations
      reflect two distinct mechanisms producing opposite effects: Perceptual load
      eliminates distractor interference, whereas sensory limitations enhance it. Tsal
      and Benoni (2010a) suggested that these results may have been due to the
      confounding effect of dilution--that is, to the presence (perceptual load) or
      absence (sensory load) of neutral items capable of diluting distractor
      interference. In the present study, we jointly manipulated dilution with
      perceptual load and with sensory degradation. The results show that, with both
      perceptual and sensory manipulations, the presence of diluting items eliminates
      distractor interference, whereas controlling for dilution increases distractor
      interference. We therefore conclude that perceptual and sensory limitations are
      just two aspects of task difficulty.

PMID- 22467355
TI  - Application of Y(2)O(3):Er(3+) nanorods in dye-sensitized solar cells.
AB  - Y(2)O(3):Er(3+) nanorods are synthesized by means of a hydrothermal method and
      then introduced into a TiO(2) electrode in a dye-sensitized solar cell (DSSC).
      Y(2)O(3):Er(3+) improves infrared light harvest via up-conversion luminescence
      and increases the photocurrent of the DSSC. The rare earth ions improve the
      energy level of the TiO(2) electrode through a doping effect and thus increase
      the photovoltage. The light scattering is ameliorated by the one-dimensional
      nanorod structure. The DSSC containing Y(2)O(3):Er(3+) (5 wt%) in the doping
      layer achieves a light-to-electric energy conversion efficiency of 7.0%, which is
      an increase of 19.9% compared to the DSSC lacking of Y(2)O(3):Er(3+).

PMID- 22467356
TI  - Prevalence of measles, mumps, rubella, and varicella susceptibility among health
      science students in a University in India.
AB  - BACKGROUND: Health science students (HSS) are at increased risk of contracting
      and transmitting viral diseases such as measles, mumps, rubella, and varicella
      (chickenpox). This study was undertaken to determine the prevalence of
      susceptibility of HSS to these infections. METHODS: Using a cross-sectional
      design, 790 HSS of Manipal University, Manipal, India, answered a questionnaire
      and provided a blood sample which was tested for specific IgG antibodies to
      measles, mumps, rubella and varicella by ELISA (Enzygnost((r))). RESULTS: The
      study group was comprised of medical (53.9%), nursing (16.6%), and allied health
      (29.5%) students. Among the overall group (n = 790), the prevalence of
      serological susceptibility to measles, mumps, rubella, and varicella were 9.5%,
      32.0%, 16.6%, and 25.8%, respectively. Among the subgroup of vaccinated subjects,
      susceptibility to measles, mumps, rubella, and varicella were 7.9%, 34.7%, 10.7%,
      and 35.2%, respectively. CONCLUSION: HSS susceptible to measles, mumps, rubella,
      and/or varicella are at risk of acquiring these diseases during their training
      period. In addition, they may be a potential source for nosocomial transmission
      posing a risk to immunocompromised patients. Hence, in the Indian setting, HSS
      should be immunized against measles, mumps, rubella, and varicella at the time of
      joining the medical school.

PMID- 22467357
TI  - Using mobile telepsychiatry to close the mental health gap.

PMID- 22467358
TI  - Neighborhood socioeconomic status modifies the association between individual
      smoking status and PAH-DNA adduct levels in prostate tissue.
AB  - Interactions between smoking and neighborhood-level socioeconomic status (SES) as
      risk factors for higher polycyclic aromatic hydrocarbon (PAH) DNA adduct levels
      in prostate tissue were investigated. PAH-DNA adducts were measured by
      immunohistochemistry with staining intensity measured in optical density units by
      semiquantitative absorbance image analysis in tumor adjacent tissue from 400
      prostatectomy specimens from the Henry Ford Health System in Detroit. For each
      subject, their U.S. Census tract of residence was classified as being of higher
      or lower SES using the median value of the distribution of the proportion of
      tract residents with a high-school education. Generalized estimating equation
      models were used to assess interactions between neighborhood-level SES and
      smoking status, adjusting for race, age, education level, tumor volume, primary
      Gleason grade and prostate specific antigen (PSA) at diagnosis. There was a
      statistical interaction (P = 0.004) between tract-level SES and smoking status.
      In lower SES tracts smoking status was not associated with adduct staining, but
      in higher SES tracts adduct staining intensity was 13% (P = 0.01) higher in ever
      smokers as compared to never-smokers. Among never-smokers, living in a lower SES
      tract was associated with a 25% higher mean staining intensity (P < 0.001).
      Neighborhood SES modifies the association between individual smoking status and
      PAH-DNA adduct levels in prostate tissue.

PMID- 22467359
TI  - Loss of compliance in small arteries, but not in conduit arteries, after 6 weeks
      exposure to high fat diet.
AB  - Arterial stiffness is a key marker in metabolic diseases and can be evaluated by
      arterial compliance. Most compliance measurements are performed in large conduit
      arteries in advanced stage of metabolic diseases, which may not provide
      information on mechanisms associated with the initiation of the pathology. For
      this reason, we compared arterial compliance of two different size arteries:
      carotid and a smaller artery (thoracodorsal artery, TDA). The arterial compliance
      was compared between control and high fat-fed mice for 6 weeks. We show that the
      compliance of the TDAs was dramatically reduced in high fat-fed mice whereas the
      compliance of the carotids remained unchanged. An abundance of collagen
      deposition in the media/adventitia of the carotids and TDAs was observed in high
      fat-fed mice. These results demonstrate that the structural and mechanical
      properties of small arteries are rapidly altered even after only 6 weeks of high
      fat feeding.

PMID- 22467360
TI  - Associations of obesity and asthma with functional exercise capacity in urban
      minority adolescents.
AB  - PURPOSE: To examine the independent association of asthma and obesity and of
      their co-existence with functional exercise capacity among urban adolescents.
      METHODS: One hundred eighteen Hispanic- and African-American adolescents
      including 33 obese asthmatics, 18 normal-weight asthmatics, 38 obese non
      asthmatics, and 29 normal-weight non-asthmatics underwent anthropometric
      measures, 6-minute walk test (6MWT) as measure of functional exercise capacity
      and spirometry as measure of pulmonary function. The 6-minute walk distance
      (6MWD) was compared between the four study groups. The association of 6MWD with
      measures of lower airway obstruction, and measures of adiposity was assessed.
      RESULTS: The 6MWD was lower among the obese groups with the least distance
      covered by the obese asthmatic group (P = 0.02). In the obese asthmatic group,
      there was a negative correlation between 6MWD and body mass index (BMI) (r = 
      0.35, P = 0.03), but no association was noted with percent-predicted forced
      expiratory volume in the 1st second (FEV(1) ; r = 0.07, P = 0.70). Conversely,
      the 6MWD correlated with FEV(1) among normal-weight asthmatics (r = 0.45, P =
      0.04) and normal-weight non-asthmatics (r = 0.4, P = 0.03), but was not
      associated with BMI in either of the two groups. After adjusting for age, height,
      gender, and ethnicity, BMI was noted to be a significant predictor (beta -2.76,
      95% CI -4.77 to -0.76, P < 0.01) of the 6MWD among the obese while percent
      predicted FEV(1) (beta 1.87, 95% CI 0.28-3.45, P = 0.02) was a significant
      predictor among the normal-weight participants. CONCLUSIONS: Our findings suggest
      that among urban minority obese asthmatic adolescents, functional exercise
      capacity was associated with obesity, rather than pulmonary function.

PMID- 22467361
TI  - Psychotherapy for social anxiety disorder: long-term effectiveness of resource
      oriented cognitive-behavioral therapy and cognitive therapy in social anxiety
      disorder.
AB  - OBJECTIVE: Resource-oriented cognitive-behavioral therapy (ROCBT) and cognitive
      therapy (CT) have been shown to be effective treatments for social anxiety
      disorder. However, so far few studies have examined the long-term effectiveness
      of these treatments. Thus, there is little information available about the
      durability of change in treated patients with social anxiety disorder. DESIGN:
      This study examined the effectiveness of both treatments at 2-year and 10-year
      follow-up assessments. Patients who received ROCBT or CT were re-contacted after
      2 (n = 51), and 10 years (n = 27), respectively, and completed a battery of self
      report questionnaires. RESULTS: Treatment gains were maintained over the 2-year
      follow-up on all measures. Furthermore, there was a significant improvement on 2
      social anxiety measures between posttreatment and the 10-year follow-up. ROCBT
      and CT did not differ in overall effectiveness. CONCLUSION: The results suggest
      that both treatments are effective and durable approaches in the treatment of
      social anxiety disorder.

PMID- 22467362
TI  - Defining small eye phenotypes.

PMID- 22467363
TI  - Extraction of DNA suitable for PCR applications from mature leaves of Mangifera
      indica L.
AB  - Good quality deoxyribonucleic acid (DNA) is the pre-requisite for its downstream
      applications. The presence of high concentrations of polysaccharides,
      polyphenols, proteins, and other secondary metabolites in mango leaves poses
      problem in getting good quality DNA fit for polymerase chain reaction (PCR)
      applications. The problem is exacerbated when DNA is extracted from mature mango
      leaves. A reliable and modified protocol based on the cetyltrimethylammonium
      bromide (CTAB) method for DNA extraction from mature mango leaves is described
      here. High concentrations of inert salt were used to remove polysaccharides;
      Polyvinylpyrrolidone (PVP) and beta-mercaptoethanol were employed to manage
      phenolic compounds. Extended chloroform-isoamyl alcohol treatment followed by
      RNase treatment yielded 950-1050 ug of good quality DNA, free of protein and RNA.
      The problems of DNA degradation, contamination, and low yield due to irreversible
      binding of phenolic compounds and coprecipitation of polysaccharides with DNA
      were avoided by this method. The DNA isolated by the modified method showed good
      PCR amplification using simple sequence repeat (SSR) primers. This modified
      protocol can also be used to extract DNA from other woody plants having similar
      problems.

PMID- 22467364
TI  - Improvement of PCR reaction conditions for site-directed mutagenesis of big
      plasmids.
AB  - QuickChange mutagenesis is the method of choice for site-directed mutagenesis
      (SDM) of target sequences in a plasmid. It can be applied successfully to small
      plasmids (up to 10 kb). However, this method cannot efficiently mutate bigger
      plasmids. Using KOD Hot Start polymerase in combination with high performance
      liquid chromatography (HPLC) purified primers, we were able to achieve SDM in big
      plasmids (up to 16 kb) involving not only a single base change but also multiple
      base changes. Moreover, only six polymerase chain reaction (PCR) cycles and 0.5
      ul of polymerase (instead of 18 PCR cycles and 1.0 ul of enzyme in the standard
      protocol) were sufficient for the reaction.

PMID- 22467365
TI  - Biotransformation of nitro-polycyclic aromatic compounds by vegetable and fruit
      cell extracts.
AB  - Extracts from various vegetables and fruits were investigated for their abilities
      to reduce nitro-polycyclic aromatic hydrocarbons (NPAHs). The extracts from grape
      and onion exhibited an interesting selectivity, yielding corresponding
      hydroxylamines or amines as major products under mild conditions of 30  degrees C
      and pH 7.0. Grape extracts reduced the 4-nitro-1,8-naphthalic anhydride with the
      highest conversion rate (>99%) and the highest ratio of hydroxylamine to amine
      (95:5). In contrast, the onion extracts reduced 4-nitro-1,8-naphthalic anhydride
      with a conversion rate of 94% and a ratio of hydroxylamine to amine of 8:92. The
      thiol-reducing agent, beta-mercaptoethanol, and metal cations, Ca(2+) and Mg(2+),
      greatly increased the reductive efficiency. This work provides an alternative
      strategy for biotransformation of nitro-polycyclic compounds.

PMID- 22467366
TI  - Decontamination of Bacillus subtilis var. niger spores on selected surfaces by
      chlorine dioxide gas.
AB  - OBJECTIVE: Chlorine dioxide (CD) gas has been used as a fumigant in the
      disinfection of biosafety laboratories. In this study, some experiments were
      conducted to assess the inactivation of spores inoculated on six materials
      [stainless steel (SS), painted steel (PS), polyvinyl chlorid (PVC), polyurethane
      (PU), glass (GS), and cotton cloth (CC)] by CD gas. The main aims of the study
      were to determine the sporicidal efficacy of CD gas and the effect of
      prehumidification before decontamination on sporicidal efficacy. METHODS:
      Material coupons (1.2 cm diameter of SS, PS, and PU; 1.0 cm*1.0 cm for PVC, GS,
      and CC) were contaminated with 10 MUl of Bacillus subtilis var. niger (ATCC 9372)
      spore suspension in mixed organic burden and then dried in a biosafety cabinet
      for 12 h. The spores were recovered by soaking the coupons in 5 ml of extraction
      liquid for 1 h and then vortexing the liquid for 1 min. RESULTS: The log
      reductions in spore numbers on inoculated test materials exposed to CD gas
      [0.080% (volume ratio, v/v) for 3 h] were in the range of from 1.80 to 6.64.
      Statistically significant differences were found in decontamination efficacies on
      test material coupons of SS, PS, PU, and CC between with and without a 1-h
      prehumidification treatment. With the extraction method, there were no
      statistically significant differences in the recovery ratios between the porous
      and non-porous materials. CONCLUSIONS: The results reported from this study could
      provide information for developing decontamination technology based on CD gas for
      targeting surface microbial contamination.

PMID- 22467367
TI  - Acaricidal activities of whole cell suspension, cell-free supernatant, and crude
      cell extract of Xenorhabdus stokiae against mushroom mite (Luciaphorus sp.).
AB  - Xenorhabdus bacterium has been used as a biological control agent against
      Luciaphorus sp., a mushroom mite endemic in Thailand. To develop an effective
      formulation of Xenorhabdus stokiae, treatments using different parts of X.
      stokiae isolate PB09 culture, including whole cell suspension, cell-free
      supernatant, and crude cell extract, were performed. The results show that
      different parts of X. stokiae isolate PB09 culture could induce variable effects
      on mite mortality and fecundity. Application with cell-free supernatant of X.
      stokiae culture resulted in both the highest mite mortality rate [(89.00+/
      3.60)%] and the lowest mite fecundity [(41.33+/-23.69) eggs/gravid female]. Whole
      cell suspension of X. stokiae isolate PB09 culture was found to be slightly less
      effective than its cell-free supernatant, suggesting that X. stokiae was more
      likely to release its metabolites with acaricidal activities to the surrounding
      culture media. Crude cell extract of X. stokiae was not effective against mites.
      Cell-free supernatant of X. stokiae isolate PB09 was the most effective
      biological control agent and it could be conveniently used in future formulations
      instead of live bacteria.

PMID- 22467368
TI  - Determination of organophosphorus pesticide residues in vegetables by an enzyme
      inhibition method using alpha-naphthyl acetate esterase extracted from wheat
      flour.
AB  - The widespread use of organophosphorus pesticides (OPs) poses a great threat to
      human health and has made the detection of OP residues in food an important task,
      especially in view of the fact that easy and rapid detection methods are needed.
      Because OPs have inhibitory effects on the activity of alpha-naphthyl acetate
      esterase (ANAE) in plants, in this work we evaluated the possibility of detecting
      OPs in vegetables with ANAE extracted from commercial flour. The limits of
      detection (LODs) obtained for methamidophos, dichlorvos, phoxim, dimethoate, and
      malathion in lettuce samples with crude ANAE were 0.17, 0.11, 0.11, 0.96, and
      1.70 mg/kg, respectively. Based on the maximum residue limits (MRLs) for OPs in
      food stipulated by Chinese laws which are 0.05, 0.20, 0.05, 1.00, and 8.00 mg/kg
      for methamidophos, dichlorvos, phoxim, dimethoate, and malathion, respectively,
      the esterase inhibition method with crude ANAE had sufficient sensitivity to
      detect the residues of dichlorvos, dimethoate, and malathion in lettuce, but it
      could not be used to guarantee the safety of the same samples if methamidophos or
      phoxim residue was present. The sensitivity of the method was improved by the use
      of esterase purified by ammonium sulfate salting-out. The LODs obtained for
      methamidophos and phoxim with purified esterase were lower than the MRLs for
      these OPs in food. This is a very promising method for the detection of OP
      residues in vegetables using crude or purified esterase because of its cheapness,
      sensitivity, and convenience.

PMID- 22467369
TI  - Fertilization increases paddy soil organic carbon density.
AB  - Field experiments provide an opportunity to study the effects of fertilization on
      soil organic carbon (SOC) sequestration. We sampled soils from a long-term (25
      years) paddy experiment in subtropical China. The experiment included eight
      treatments: (1) check, (2) PK, (3) NP, (4) NK, (5) NPK, (6) 7F:3M (N, P, K
      inorganic fertilizers+30% organic N), (7) 5F:5M (N, P, K inorganic
      fertilizers+50% organic N), (8) 3F:7M (N, P, K inorganic fertilizers+70% organic
      N). Fertilization increased SOC content in the plow layers compared to the non
      fertilized check treatment. The SOC density in the top 100 cm of soil ranged from
      73.12 to 91.36 Mg/ha. The SOC densities of all fertilizer treatments were greater
      than that of the check. Those treatments that combined inorganic fertilizers and
      organic amendments had greater SOC densities than those receiving only inorganic
      fertilizers. The SOC density was closely correlated to the sum of the soil carbon
      converted from organic amendments and rice residues. Carbon sequestration in
      paddy soils could be achieved by balanced and combined fertilization.
      Fertilization combining both inorganic fertilizers and organic amendments is an
      effective sustainable practice to sequestrate SOC.

PMID- 22467370
TI  - Spermidine affects the transcriptome responses to high temperature stress in
      ripening tomato fruit.
AB  - OBJECTIVE: High temperature adversely affects quality and yield of tomato fruit.
      Polyamine can alleviate heat injury in plants. This study is aimed to investigate
      the effects of polyamine and high temperature on transcriptional profiles in
      ripening tomato fruit. METHODS: An Affymetrix tomato microarray was used to
      evaluate changes in gene expression in response to exogenous spermidine (Spd, 1
      mmol/L) and high temperature (33/27  degrees C) treatments in tomato fruits at
      mature green stage. RESULTS: Of the 10101 tomato probe sets represented on the
      array, 127 loci were differentially expressed in high temperature-treated fruits,
      compared with those under normal conditions, functionally characterized by their
      involvement in signal transduction, defense responses, oxidation reduction, and
      hormone responses. However, only 34 genes were up-regulated in Spd-treated fruits
      as compared with non-treated fruits, which were involved in primary metabolism,
      signal transduction, hormone responses, transcription factors, and stress
      responses. Meanwhile, 55 genes involved in energy metabolism, cell wall
      metabolism, and photosynthesis were down-regulated in Spd-treated fruits.
      CONCLUSIONS: Our results demonstrated that Spd might play an important role in
      regulation of tomato fruit response to high temperature during ripening stage.

PMID- 22467371
TI  - Natural populations of lactic acid bacteria in douchi from Yunnan Province,
      China.
AB  - This research was aimed at isolating and identifying the predominant lactic acid
      bacteria (LAB) in the traditional Chinese salt-fermented soybean food, douchi,
      from Yunnan, China. The predominant LAB present were isolated and identified by
      conventional culture-dependent methods combined with molecular biological
      methods. Two hundred and sixty isolates were obtained from thirty kinds of
      traditional fermented douchi from six cities and counties in Yunnan, and those
      strains were divided into twelve groups by their morphological and biochemical
      characteristics. Based on 16S ribosomal DNA (rDNA) sequencing and analysis, 56
      representative strains were identified as belonging to 6 genera and 14 species:
      Lactobacillus (4 spp.), Weissella (3 spp.), Pediococcus (2 spp.), Staphylococcus
      (2 spp.), Enterococcus (1 sp.), and Bacillus (2 spp.). The results show that
      douchi contains a large natural population of LAB of diverse composition from
      which some strains could be selected as starters for functional fermented foods.
      This is the first study on the original douchi from Yunnan, and the results
      suggest that it may be a useful source for the isolation of LAB. This study has
      also laid a foundation for further research on developing functional douchi
      products.

PMID- 22467372
TI  - Long-term high fructose and saturated fat diet affects plasma fatty acid profile
      in rats.
AB  - As the consumption of fructose and saturated fatty acids (FAs) has greatly
      increased in western diets and is linked with an increased risk of metabolic
      syndrome, the aim of this study was to investigate the effects of a moderate (10
      weeks) and a prolonged (30 weeks) high fructose and saturated fatty acid (HFS)
      diet on plasma FA composition in rats. The effects of a few weeks of HFS diet had
      already been described, but in this paper we tried to establish whether these
      effects persist or if they are modified after 10 or 30 weeks. We hypothesized
      that the plasma FA profile would be altered between 10 and 30 weeks of the HFS
      diet. Rats fed with either the HFS or a standard diet were tested after 10 weeks
      and again after 30 weeks. After 10 weeks of feeding, HFS-fed rats developed the
      metabolic syndrome, as manifested by an increase in fasting insulinemia, total
      cholesterol and triglyceride levels, as well as by impaired glucose tolerance.
      Furthermore, the plasma FA profile of the HFS group showed higher proportions of
      monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],
      whereas the proportions of some polyunsaturated n-6 FAs, such as linoleic acid
      [18:2(n-6)] and arachidonic acid [20:4(n-6)], were lower than those in the
      control group. After 30 weeks of the HFS diet, we observed changes mainly in the
      levels of 16:1(n-7) (decreased) and 20:4(n-6) (increased). Together, our results
      suggest that an HFS diet could lead to an adaptive response of the plasma FA
      profile over time, in association with the development of the metabolic syndrome.

PMID- 22467373
TI  - Alleviative effect of quercetin on germ cells intoxicated by 3-methyl-4
      nitrophenol from diesel exhaust particles.
AB  - As a component of diesel exhaust particles, 3-methyl-4-nitrophenol (4-nitro-m
      cresol, PNMC) is also a metabolite of the insecticide fenitrothion and imposes
      hazardous effects on human health. In the present study, the alleviative effect
      of a common antioxidant flavonoid quercetin on mouse germ cells intoxicated by
      PNMC was investigated. Results showed that a single intraperitoneal injection of
      PNMC at 100 mg/kg induced severe testicular damage after one week. PNMC-treated
      mice showed a significant loss of germ cells (approximate 40% loss of round germ
      cells). PNMC caused an increase of hydroxyl radical and hydrogen peroxide
      production and lipid peroxidation, as well as a decrease in glutathione level,
      superoxide dismutase and glutathione peroxidase activities. Furthermore,
      treatment of PNMC increased expression of the pro-apoptotic protein Bax and
      decreased expression of the anti-apoptotic protein Bcl-XL in germ cells. In
      addition, testicular caspase-3 activity was significantly up-regulated and germ
      cell apoptosis was significantly increased in the PNMC-treated mice. In contrast,
      combined administration of quercetin at 75 mg/kg significantly attenuated PNMC
      induced testicular toxicity. These results indicate that the antioxidant
      quercetin displays a remarkable protective effect on PNMC-induced oxidative
      damage in mouse testes and may represent an efficient supplement to attenuate
      reproductive toxicity by environmental toxicants to ensure healthy sperm
      production.

PMID- 22467375
TI  - Supercritical fluid deposition of uniform PbS nanoparticle films for energy
      transfer studies.
AB  - Using supercritical fluid CO(2) (Sc-CO(2)) as a medium, PbS nanoparticles can be
      uniformly deposited on surfaces of various substrates. Sc-CO(2) deposition of PbS
      nanoparticles on carbon-coated copper grids, into small holes in silicon, and
      formation of uniform PbS nanoparticle films on glass are described. Fluorescence
      spectra of PbS nanoparticles obtained from the films prepared by the Sc-CO(2)
      method indicate effective energy transfer between PbS nanoparticles of different
      sizes.

PMID- 22467374
TI  - Application of biomonitoring and support vector machine in water quality
      assessment.
AB  - The behavior of schools of zebrafish (Danio rerio) was studied in acute toxicity
      environments. Behavioral features were extracted and a method for water quality
      assessment using support vector machine (SVM) was developed. The behavioral
      parameters of fish were recorded and analyzed during one hour in an environment
      of a 24-h half-lethal concentration (LC(50)) of a pollutant. The data were used
      to develop a method to evaluate water quality, so as to give an early indication
      of toxicity. Four kinds of metal ions (Cu(2+), Hg(2+), Cr(6+), and Cd(2+)) were
      used for toxicity testing. To enhance the efficiency and accuracy of assessment,
      a method combining SVM and a genetic algorithm (GA) was used. The results showed
      that the average prediction accuracy of the method was over 80% and the time cost
      was acceptable. The method gave satisfactory results for a variety of metal
      pollutants, demonstrating that this is an effective approach to the
      classification of water quality.

PMID- 22467376
TI  - A case series of atypical presentations of thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a heterogeneous disease primarily
      characterized by thrombocytopenia and microangiopathic hemolytic anemia.
      Therapeutic plasma exchange has dramatically improved mortality, allowing for
      emergence of refractory, relapsing, and atypical presentations. In this article,
      we describe four cases of TTP presenting with minimal schistocytes, mild
      elevation of lactate dehydrogenase, and symptoms suggestive of macrovascular
      arterial involvement. With increasing reports of less common presentations of
      TTP, clinicians should consider this diagnosis in cases of unexplained arterial
      thrombosis, thrombocytopenia, or hemolytic anemia. Testing for a disintegrin and
      metalloprotease with thrombospondin Type 1 motif, Member 13 ADAMTS13 activity was
      extremely useful to help confirm the diagnosis in our series of patients.

PMID- 22467377
TI  - Safety and cost-effectiveness of a clinical protocol implemented to standardize
      the use of Crotalidae polyvalent immune Fab antivenom at an academic medical
      center.
AB  - STUDY OBJECTIVE: To evaluate the safety and cost-effectiveness of a clinical
      protocol adopted in June 2006 that included a comprehensive, objective assessment
      of snake bite envenomations and standardized the use of Crotalidae polyvalent
      immune Fab antivenom (FabAV). DESIGN: Retrospective medical record review.
      SETTING: Academic medical center that serves as the regional level I trauma
      center. PATIENTS: Seventy-five adults treated with FabAV for snake envenomations
      in the emergency department between June 1, 2003, and June 1, 2009; 30 patients
      received treatment according to the protocol (treatment group), and 45 patients
      received treatment that did not adhere to the protocol (control group).
      MEASUREMENTS AND MAIN RESULTS: Demographic and envenomation characteristics, as
      well as treatment details, were collected for all patients. In addition,
      information on quantity of FabAV vials required, length of hospital stay, and
      length of intensive care unit stay were compared between the treatment and
      control groups. In the treatment group, significantly fewer vials of FabAV were
      used (2.5 vs 4.727 vials, p=0.007). This decreased in usage correlated to a cost
      savings of approximately $2000/patient. Despite no significant difference in the
      severity of the envenomations between the two groups (p=0.379), the treatment
      group experienced a significantly shorter hospital length of stay (1.933 vs 2.791
      days, p=0.030). No significant difference in the progression to fasciotomy or the
      development of allergic reactions was noted between the two groups. CONCLUSION:
      Use of a clinical protocol related to snake envenomations resulted in
      approximately two fewer vials of FabAV required for each patient. In addition,
      the treatment group experienced a shorter hospital length of stay without a
      corresponding increase in adverse events or envenomation progression. Data show
      that use of the protocol was cost-effective. The development of institution
      specific multidisciplinary protocols regarding snake bite envenomations is
      recommended. Clinical pharmacists can play a vital role in the protocol
      development to ensure that optimal care is provided for this distinct patient
      population.

PMID- 22467378
TI  - Genomic instability in chronic renal failure patients.
AB  - Patients suffering chronic renal failure (CRF) exhibit a high incidence of
      cancer, as well as high levels of genetic damage. We hypothesized that these
      patients show genomic instability as measured by increased radiosensitivity to
      the induction of genetic damage. The background levels of genetic damage and the
      net genetic damage after in vitro irradiation with 0.5 Gy were analyzed using the
      micronucleus assay in peripheral blood lymphocytes of 174 CRF patients and 53
      controls. The net radiation-induced genetic damage was significantly higher in
      CRF patients with respect to controls. Among CRF patients, the levels of genetic
      damage were higher in those with prior incidence of cancer than in those without
      cancer; in addition, those CRF patients undergoing hemodialysis presented with
      higher levels of genetic damage than those in the advanced Stages (4-5) of the
      pathology. A positive association was observed between basal and net micronucleus
      frequency among CFR patients. However, no association was found between net
      genetic damage and parameters linked to the different stages of the pathology,
      such as urine creatinine levels and glomerular filtration rate. Our results
      indicate that CRF patients show increased radiosensitivity and that the degree of
      radiosensitivity is associated with the progression of the pathological stage of
      the disease.

PMID- 22467379
TI  - A three-dimensionally ordered macroporous carbon derived from a natural resource
      as anode for microbial bioelectrochemical systems.
AB  - Top of the crops: The direct use of a natural three-dimensional (3D) architecture
      in microbial fuel cells (MFCs) is reported for the first time. Stems from the
      crop plant kenaf (Hibiscus cannabinus) are carbonized and used as anode material
      in MFCs. The current density generated by the carbon is comparable to that of
      other 3D anodes prepared by other methods. The renewable and low-cost
      characteristics of this material provide an excellent basis for large-scale
      application in microbial bioelectrochemcial systems.

PMID- 22467380
TI  - Exercise in inflammatory myopathies, including inclusion body myositis.
AB  - Exercise is an important part of treatment in patients with idiopathic
      inflammatory myopathies. Improved functioning, ability to perform activities of
      daily living, and health-related quality of life have been reported in adult
      polymyositis, dermatomyositis, and also recently inclusion body myositis
      following different exercise regimens, with no signs of increased muscle
      inflammation. Intensive resistance training could reduce clinical disease
      activity and reduce expression of genes regulating inflammation and fibrosis in
      chronic polymyositis and dermatomyositis. Today, exercise research in adult
      myositis is focused on understanding mechanisms for muscle impairment and
      improved muscle function in relation to exercise and verifying results from
      small, open studies in larger settings. There are no studies evaluating the
      effects of exercise over weeks or months in juvenile dermatomyositis, other than
      a case report; however, there is to our knowledge an ongoing effort to evaluate
      the safety and effects of exercise in patients with juvenile dermatomyositis.

PMID- 22467381
TI  - Development of the brief inventory of perceived stress.
AB  - OBJECTIVES: To provide a measure of perceived stress that is psychometrically
      superior to existing instruments and novel in dimensionality. DESIGN: At 4-week
      intervals over 48 weeks, patients with multiple sclerosis (N = 138) completed 26
      items from the Perceived Stress Scale (PSS) and the Perceived Stress
      Questionnaire (PSQ). RESULTS: Extant factor analytic models of the PSS fit
      poorly. A new measure using nine PSS and PSQ items, the Brief Inventory of
      Perceived Stress (BIPS), demonstrated good fit, construct validity, and stability
      with 3 factors: Lack of Control, Pushed, and Conflict and Imposition.
      CONCLUSIONS: Items commonly used to measure perceived stress may have a more
      sophisticated underlying structure than previously thought. The BIPS's
      multidimensionality and longitudinal stability offer potential benefits in
      conceptualization and outcome prediction.

PMID- 22467382
TI  - Influence of pill burden and drug cost on renal function after transplantation.
AB  - STUDY OBJECTIVE: To determine the influence of pill burden and drug cost on
      outcomes after renal transplantation. DESIGN: Retrospective medical record
      review. SETTING: Kidney and pancreas transplantation center. PATIENTS: Sixty
      eight adults who underwent kidney or kidney-pancreas transplantation during 2007.
      MEASUREMENTS AND MAIN RESULTS: The median pretransplantation pill burden was 15
      pills/day, which increased to 25 pills/day at 1 month after transplantation and
      returned to 16 pills/day by 1 year after transplantation. Pretransplantation pill
      burden was lower than the burden at 1, 3, 6, 12, and 24 months after
      transplantation (p<0.05). The mean pretransplantation drug cost of $1918/month
      was lower than the cost at 1 month after transplantation ($2564/mo, p=0.04) but
      was similar thereafter. Higher pretransplantation pill burden was associated with
      increased serum creatinine concentration at 6 months after transplantation
      (r=0.288, p=0.017). Higher pill burdens at 1 month (r=0.364, p=0.002), 3 months
      (r=0.332, p=0.006), and 6 months (r=0.374, p=0.002) were associated with
      increased 3-month serum creatinine concentration. Higher drug costs were
      associated with increased serum creatinine concentrations throughout the study.
      CONCLUSION: Higher pretransplantation pill burden and higher drug cost may be
      associated with poor renal function after transplantation. Further study
      addressing factors associated with nonadherence is needed.

PMID- 22467383
TI  - Extracorporeal photopheresis: clinical use so far.
AB  - Extracorporeal photopheresis (ECP or photopheresis) is an advanced therapeutic
      apheresis procedure in which blood is separated into its various components and
      the isolated buffy coat is treated with 8-methoxypsoralen (a photoactivating
      drug), exposed to ultraviolet light and returned to the patient. All other
      remaining blood components are also returned to the patient. The purpose of this
      procedure is immunomodulation. The treated leukocytes, specifically T-cells, are
      returned to the patient's circulation and will induce cytotoxicity and reduce
      proliferation of new T-cells. In the United States, ECP was initially approved
      for the treatment of cutaneous T-cell lymphoma by the US Food and Drug
      Administration in the late 1980s. Since that time, it has been used as an "off
      label" therapy to treat several other autoimmune diseases in the United States
      and even more extensively in Europe and Asia. The following review is limited to
      the current clinical use of ECP in cutaneous T-cell lymphoma, Crohn's disease,
      systemic sclerosis, graft versus host disease, and emerging data on nephrogenic
      systemic fibrosis.

PMID- 22467384
TI  - Duty-related trauma exposure in 911 telecommunicators: considering the risk for
      posttraumatic stress.
AB  - Peritraumatic distress may increase the risk for posttraumatic stress disorder
      (PTSD) in police officers. Much less is known about emotional reactions and PTSD
      symptomatology in 911 telecommunicators. The current study assessed duty-related
      exposure to potentially traumatic calls, peritraumatic distress, and PTSD
      symptomatology in a cross-sectional, convenience sample of 171 telecommunicators.
      Results showed that telecommunicators reported high levels of peritraumatic
      distress and a moderate, positive relationship was found between peritraumatic
      distress and PTSD symptom severity (r = .34). The results suggest that 911
      telecommunicators are exposed to duty-related trauma that may lead to the
      development of PTSD, and that direct, physical exposure to trauma may not be
      necessary to increase risk for PTSD in this population.

PMID- 22467385
TI  - Cranial morphometric study of four giant flying squirrels (Petaurista) (Rodentia:
      Sciuridae) from China.
AB  - The present study revisited the controversial taxonomic status of Petaurista
      yunanensis, P. philippensis, P. hainana, and P. petaurista by using a
      considerably extended set of morphometrical characters (26 cranial variables from
      60 adult specimen skulls). The results revealed no sexual dimorphism in any of
      the four species but confirmed significant craniometric differences among the
      four species in both the principal components analysis (PCA) and discriminant
      function analysis (DFA), with the greatest distinction observed between P.
      petaurista and other Petaurista species. Both univariate and multivariate
      analysis indicated that the morphological differences between P. yunanensis and
      P. philippensis were less than that between P. philippensis and P. hainana. The
      morphometric results were concordant in geographic patterns with mtDNA data from
      previous studies and indicated that P. petaurista, P. hainana, P. philippensis,
      and P. yunanensis could be recognized as valid species.

PMID- 22467386
TI  - [Phylogeny and genetic diversity of Phrynocephalus przewalskii].
AB  - Phrynocephalus przewalskii is one kind of lizards inhabiting inclusively in the
      desert that has controversial viewpoints on its phylogeny. Based on mitochondrial
      ND2 gene of 119 samples from 12 geographic populations, we analyzed the effects
      of environmental factors on the variation of genetic diversity, as well as its
      relationship to P. versicolor. The results showed that these populations
      clustered into three major lineages, with P. versicolor embedded within one
      lineage. The twelve populations had great genetic diversity variation, which was
      tightly linked with local altitude, annual precipitation, and variation of annual
      precipitation. High latitudes, increased annual precipitation and great variation
      in annual precipitations may all have resulted in the decrease of genetic
      diversity. It thus assumed that altitude can change the genetic diversity of
      different geographic populations of P. przewalskii resulting from the effects of
      different local annual precipitation.

PMID- 22467387
TI  - Complete mitochondrial genome of the five-dot sergeant Parathyma sulpitia
      (Nymphalidae: Limenitidinae) and its phylogenetic implications.
AB  - The complete mitochondrial genome of the Parathyma sulpitia (Lepidoptera,
      Nymphalidae, Limenitidinae) was determined. The entire mitochondrial DNA (mtDNA)
      molecule was 15 268 bp in size. Its gene content and organization were the same
      as those of other lepidopteran species, except for the presence of the 121 bp
      long intergenic spacer between trnS1(AGN) and trnE. The 13 protein-coding genes
      (PCGs) started with the typical ATN codon, with the exception of the cox1 gene
      that used CGA as its initial codon. In addition, all protein-coding genes
      terminated at the common stop codon TAA, except the nad4 gene which used a single
      T as its terminating codon. All 22 tRNA genes possessed the typical clover leaf
      secondary structure except for trnS1(AGN), which had a simple loop with the
      absence of the DHU stem. Excluding the A+T-rich region, the mtDNA genome of P.
      sulpitia harbored 11 intergenic spacers, the longest of which was 121 bp long
      with the highest A+T content (100%), located between trnS1(AGN) and trnE. As in
      other lepidopteran species, there was an 18-bp poly-T stretch at the 3'-end of
      the A+T-rich region, and there were a few short microsatellite-like repeat
      regions without conspicuous macro-repeats in the A+T-rich region. The
      phylogenetic analyses of the published complete mt genomes from nine Nymphalidae
      species were conducted using the concatenated sequences of 13 PCGs with maximum
      likelihood and Bayesian inference methods. The results indicated that
      Limenitidinae was a sister to the Heliconiinae among the main Nymphalidae
      lineages in this study, strongly supporting the results of previous molecular
      data, while contradicting speculations based on morphological characters.

PMID- 22467388
TI  - Bacterial expression and purification of biologically active human TFF2.
AB  - Human trefoil factor 2 (hTFF2) is considered as one of the most important
      initiators of mucosal healing in the gastrointestinal tract by promoting cell
      migration and suppressing apoptosis. However, it is hard to obtain hTFF2 from
      human tissue and many recombinant hTFF2 produced in vitro exist as fusion
      proteins. The purpose of the present study was to produce native hTFF2 while
      maintaining its biological activities. The open reading frame of hTFF2 was
      inserted into a pET-32a(+) expression vector, and hTFF2-TRX fusion protein was
      successfully expressed in Escherichia coli and purified by Nickel
      nitrilotriacetic acid affinity chromatography and reverse-phase HPLC steps. The
      recombinant fusion protein (purity>95%) was cleaved by Factor Xa at 23 Degrees
      Celsius to release hTFF2. After removal of Factor Xa and undigested fusion
      proteins, hTFF2 was purified and identified by SDS-PAGE and Western blotting. The
      yield of recombinant hTFF2 was about 5 mg/L. The recombinant hTFF2 could promote
      IEC-6 cells migration and in vitro wound healing via the activation of ERK1/2.
      Recombinant hTFF2 could also inhibit apoptosis of HCT-116 cells induced by 50
      MUmol/L ceramide. In summary, our results showed that the recombinant hTFF2 was
      expressed in E. coli and successfully purified after cleavage with the fusion
      partner with high yield while maintaining its biological activities. Recombinant
      hTFF2 might be useful for investigating the molecular mechanism of hTFF2 and
      development of hTFF2-related drugs.

PMID- 22467389
TI  - [Molecular cloning, sequence analysis and expression of ayu complement component
      C9 gene].
AB  - C9, a component of the membrane attack complex, participates in the final stage
      of the complement cascade which lyses foreign organisms by disrupting the
      integrity of their cell membranes. In the present study, a full-length ayu C9
      (aC9) cDNA was cloned which contains 2,125 nucleotides and encodes a protein of
      592 amino acids. A signal peptide was deposited in the N-terminal 22 residues.
      The deduced amino acid sequence of aC9 showed 56.8% identity to the C9 of rainbow
      trout, and 40.9% to 53.8% identity to the C9 of other teleosts. RT-PCR analysis
      demonstrated that the mRNA of aC9 was expressed in the liver, spleen, intestine,
      gill and muscle of healthy ayu fish with the highest level in the liver.
      Quantitative RT-PCR analysis showed that aC9 transcripts were significantly up
      regulated in the liver at 4 h post Listonella anguillarum infection, peaked at 16
      h post injection. Western blotting analysis revealed that serum aC9 significantly
      increased in Listonella anguillarum infected ayu fish. Our results suggested that
      aC9 may play an important role in fish immune response of anti-bacteria.

PMID- 22467390
TI  - [Cloning and expression of Tbx3 gene in Siberian sturgeon, Acipenser baerii].
AB  - Tbx3, a member of the TBX2 subfamily of T-box gene family, encodes a
      transcription factor with a highly conserved DNA-binding domain, which called T
      domain. Tbx3 is involved in morphogenesis and organogenesis in vertebrates, such
      as limb development, heart remodeling, and neural placode differentiation. In the
      present study, a full-length 2  908 bp Tbx3 cDNA from Acipenser baerii (AbTbx3)
      was obtained using RT-PCR and RACE technique, which includes a 2  166 bp complete
      open reading frame encoding a putative peptide of 721 amino acids. AbTbx3 shares
      73.5% identity with its human homolog. Particularly, the DNA-binding domain of
      AbTbx3 shared 95.2% identity with human Tbx3. Phylogenetic analysis revealed that
      AbTbx3 was grouped with Tbx3s in other vertebrates, which were clustered with
      Tbx2s and separated from Tbx4/5s. The predicted secondary and three-dimensional
      structures of the T-domain of AbTbx3 were remarkably similar to human Tbx3.
      Through semi-quantity RT-PCR, the expression of AbTbx3 was first detected at
      blastula stage during Siberian sturgeon embryonic development, increased
      gradually, reached its peak at early tail-bud stage and then decreased slightly.
      In adult sturgeon, AbTbx3 was strongly expressed in eye, brain, gill, intestines,
      pectoral fin and pelvic fin, but not in liver, blood, heart, kidney and muscle.
      The whole mount in situ hybridization showed that AbTbx3 was mainly expressed in
      the otic vesicle, hindbrain, dorsal notochord, pineal organ and dorsal fin bud in
      the larvae of stage 37 and 43.

PMID- 22467391
TI  - [Effects of odor cue on morphine-induced dependence and craving in mice].
AB  - The olfactory system may play a pivotal role in drug addiction. To clarify the
      issues, we investigated the morphine dependence and psychological craving in
      morphine addicted mice using the conditioned place preference (CPP) paradigm by
      taking an only odor cue as the conditioned stimulus (CS). The results showed that
      by pairing morphine with odor, the CPP could be induced in mice. When the
      morphine addicted mice were exposed to a novel environment during morphine
      withdrawal, they spent significantly longer time in the chamber with morphine
      paired odor than in the control chamber. The effects of odor cue on the morphine
      CPP were blocked by the administration of dopamine D1 or D2 antagonists. The
      studies indicated that olfactory system plays an important role in drug
      addiction.

PMID- 22467392
TI  - [Habitat selection of four sympatric pheasants in Guanshan National Nature
      Reserve, Jiangxi, China].
AB  - Habitat selection of four sympatric pheasants (Syrmaticus ellioti, Lophura
      nycthemera, Pucrasia macrolopha and Bumbusicola thoracica) was studied in
      Guanshan National Nature Reserve, Jiangxi, China from October 2009 to November
      2010. We measured seventeen ecological factors across 388 sites used by the four
      pheasants by direct observation in six transects. The results show that the
      pheasants preferred broad-leaved forest and coniferous forest and a sunny or semi
      shaded slope. There were differences in elevation, degree of slope, arbor
      coverage, shrub coverage, shrub quantity, shrub height, herbage cover, herbage
      species, herbage quantity, leaf litter coverage, distance to water and arbor
      species between the habitat selected by the four pheasants. Canonical scores
      indicated that the four pheasants differed in habitat selection to some extent. A
      stepwise discriminant analysis revealed that elevation, herbage quantity, shrub
      height, distance to water, shrub cover, arbor cover, degree of slope, leaf litter
      cover, shrub quantity and herbage cover were the critical factors distinguishing
      habitat selection between the species. Predicted classification accuracy of the
      model was 74.7%.

PMID- 22467393
TI  - [Dietary differences and niche partitioning in three sympatric Myotis species].
AB  - The morphology and diet characteristics of three Myotis species roosting in the
      same cave were studied in Anlong County, Guizhou from September to November 2005.
      The three mouse-eared bats were the Chinese water myotis (Myotis laniger) "body
      mass: (4.46+/-0.53) g, forearm: (34.63+/-1.45 mm)", fringed long-footed myotis
      (Myotis fimbriatus) "body mass: (5.15+/-1.76) g, forearm: (35.20+/-1.07) mm" and
      szechwan myotis (Myotis altarium) "body mass: (10.94+/-0.87) g, forearm: (45.21+/
      1.15) mm". There were significant differences in the body masses of the three
      species. The forearm length of M. altarium was significantly longer than the
      other two species. M. laniger preyed mostly on dipsters and their larvae (79.7%
      in volume and 100% in frequency, Diptera). M. fimbriatus preyed mostly on
      dipsters and small beetles (59.6% and 91.3%, Diptera; 28.8% and 80.1%,
      Coleoptera). The prey of M. altarium was mostly ground-dwelling beetles (80.8%
      and 100%, Carabidae and Silphidae, Coleoptera). These dietary examinations
      indicate that the three species are highly adapted to different foraging
      habitats. Our work suggests that the spatial differences in foraging niches and
      trophic resource partitioning represent the major mechanism behind the levels of
      co-existence seen in this particular bat community.

PMID- 22467394
TI  - [Spatial distribution of fig wasps in syconia of two monoecious Ficus sp].
AB  - In addition to pollinator fig wasps, there are several non-pollinating fig wasps
      associated with monoecious Ficus sp. In order to understand how pollinator fig
      wasps and non-pollinating fig wasps are distributed across the same syconium, the
      spatial distribution of fig wasps associated with Ficus altissima and F.
      benjamina were compared using the pedicle lengths of galls containing each
      species. The results indicate that in Ficus altissima, the average pedicel length
      of galls containing Eupristina sp. is longer than that containing E. altissima.
      Average pedicel length of galls containing Sycobia sp., Micranisa ralianga and
      Sycoscapter sp. two did not show significant difference. The range of pedicel
      lengths of galls containing Sycobia sp., M. ralianga or Sycoscapter sp. two is
      narrower than that of galls containing E. altissima, indicating these non
      pollinating fig wasps and pollinator have partially separated spatial niches. In
      F. benjamina, E. koningsbergeri was distributed in galls from the outer layer to
      inner layer, while most Walkerella sp. were found in outer layer galls,
      indicating E. koningsbergeri and Walkerella sp. have partially separated spatial
      niches.

PMID- 22467395
TI  - A new spider species of the genus Sudharmia from Sumatra, Indonesia (Araneae,
      Liocranidae).
AB  - A new spider species, Sudharmia tridenticula sp. nov., is described from primary
      evergreen forests of Sumatra, Indonesia.

PMID- 22467396
TI  - Complete mitogenome of the Lesser Purple Emperor Apatura ilia (Lepidoptera:
      Nymphalidae: Apaturinae) and comparison with other nymphalid butterflies.
AB  - The complete mitochondrial genome of Apatura ilia (GenBank accession no.
      JF437925) was determined as a circular DNA molecule of 15 242 bp, with common
      genes of 13 putative proteins, 2 rRNAs, and 22 tRNAs and of the same gene
      arrangement as in other sequenced lepidopterans. All protein-coding genes had the
      typical start codon ATN, except for the COI's using CGA as its start codon as
      previously demonstrated in other lepidopteran species. The comparison of the
      nucleotide sequences of the A. ilia mitogenome with ten other Nymphalidae species
      showed nearly identical gene orientation and arrangement, with only a few
      alterations in non-coding fragments. The nucleotide composition and codon
      frequency all fell into the range estimated for the order Lepidoptera. The A.
      ilia mitochondrial genome had the canonical set of 22 tRNA genes folded in the
      typical cloverleaf structure, with an unique exception of tRNA(Ser) (AGN). The
      mitochondrial genes from A. ilia were overlapped in a total of 33 bp at 9
      locations, as well as interleaved with a total of 155 bp intergenic spacers,
      spread over 12 regions with the size ranging from 1 to 49 bp. Furthermore, the
      spacer between ND6 and Cyt b harbored a microsatellite-like repeat (TA)(23) not
      found in other completely sequenced nymphalid genomes. The 403 bp AT-rich region
      harbored two conserved motifs (ATAGA, ATTTA), a 21 bp polyT stretch, a 10 bp poly
      A region, along with two microsatellite-like repeats ( (TA)(10) and (TA)(7)), as
      detected in other nymphalid butterflies.

PMID- 22467397
TI  - [Analysis of genetic diversity in wild populations of Trachidermus fasciatus by
      RAPD and the transformation of two SCAR markers].
AB  - Firstly, RAPD was conducted to analyze genetic diversity of Trachidermus
      fasciatus in the Fuchun River population (FR), Yellow River population (YR), Luan
      River population (LR), and Yalu River population (YL), with 32 polymorphic 10-bp
      random primers selected from 294 ones. Thirty wild individuals were detected in
      each population. The results indicated that the genetic diversity of T .
      fasciatus was relatively rich. The major results were as the following: 1)
      Altogether, 591 bands were detected and 515 of them were polymorphic, accounted
      for 87.14%. The range of proportion of polymorphic loci (P) was:
      FR(89.17%)>YR(87.99%)>YL(86.63%)>LR(83.25%). 2) The Shannon's information
      index(I(T)) and Nei's genetic diversity(H(T)) among populations were 0.3393
      0.3566 and 0.2157-0.2279, respectively. Compare to other three populations, LR
      population had relative lower values. If took the populations as a whole, the
      total Nei's genetic diversity(H(T)) and Shannon's information index(I(T)) was
      0.2336+/-0.1643 and 0.3710+/-0.2153, respectively. 3) The value of gene flow
      (N(m) ) (5.76103-19.84497) were high, indicating certain gene exchange existed
      among the four populations. But the AMOVA results exhibited significantly
      differentiation (P<0.05 or P<0.01) among the populations. 4) In the UPGMA tree
      constructed according to genetic distance, YL and YR populations clustered
      firstly, then with FR population, and finally they joined to LR population.
      Obviously, the YL, YR and FR populations had relatively close relationship
      according to their geographic distance, whereas LR population showed clear
      divergence to the other three populations. Secondly, out of the five special RAPD
      bands (S(1225)(525 bp), S(1225)(605 bp), S(1225)(841 bp), S(1345)(695 bp) and
      S(1345)(825 bp)), SCAR maker SCAR01(560 bp) and SCAR02(443 bp) were successfully
      transformed from S(1255)(605 bp) and S(1255)(841 bp), respectively. After large
      samples examination of the two markers, we found the highest frequency (96.67%
      and 93.33%) in the YL population, higher frequency (83.33% and 90%) in the FR
      population, high frequency (56.67% and 66.67%) in the YR population, and the
      lowest frequency (13.33% and 20 %) in the LR population. Therefore, SCAR01(560
      bp) and SCAR02(443 bp) can be used as special molecular markers for the
      population identification between LR and other three populations.

PMID- 22467398
TI  - [Expression of IFN-gamma, IL-1alpha, NGF-beta and TNF-alpha during the
      development of cerebellar cortex of Western Anhui white goose].
AB  - The strep avidin-biotin-peroxidase complex (SABC) immunohistochemical methods
      were applied to investigate the localization and semi-quantitative distribution
      of IFN-gamma, IL-1alpha, NGF-beta and TNF-alpha-immunoreactive cells in the
      cerebellar cortex of Western Anhui white goose at embryonic day 13, 19, 24, 28
      (E13, E19, E24, E28) and postnatal day 7, 15 (P7, P15). The possible roles of IFN
      gamma,IL-1alpha,NGF-beta and TNF-alpha in the development of cerebellar cortex
      were discussed. The results indicated that in the external granular layer, there
      were IFN-gamma and TNF-alpha positive cells at E13, E19, E24, E28, P7, IL-1alpha
      positive cells at E13, E19, E24, E28 and NGF-beta positive cells at E13, E19 ,
      E24. The expression levels of these four cytokines all reached peaks at E19 of
      the six tested periods in this study. In the Purkinje cell layer, there were IFN
      gamma, IL-1alpha and TNF-alpha positive cells at E13, E19, E24, E28, P7, P15 and
      NGF-beta positive cells at E13, E19, E24, E28, P7. In the internal granular
      layer, there were IFN-gamma positive cells at E13, E19, E24, E28, P7, P15, IL
      1alpha and TNF-alpha positive cells at E13, E19, E24, E28, P7 and NGF-beta
      positive cells at E13, E19, E24, E28. These results showed that E19 might be the
      "critical stage"in the cerebellar cortex development of Western Anhui white
      goose. IFN-gamma, IL-1alpha and TNF-alpha might be synthesized by cerebellar
      cortex itself, and NGF-beta could be transported from regions which project to
      Purkinje cells. IFN-gamma may interfer the transfer of granular cells, and NGF
      beta may have neurotrophic functions that are beneficial to the growth and
      development of Purkinje cells.

PMID- 22467399
TI  - Acute lesions of primary visual cortical areas in adult cats inactivate responses
      of neurons in higher visual cortices.
AB  - Psychophysical studies suggest that lateral extrastriate visual cortical areas in
      cats may mediate the sparing of vision largely by network reorganization
      following lesions of early visual cortical areas. To date, however, there is
      little direct physiological evidence to support this hypothesis. Using in vivo
      single-unit recording techniques, we examined the response of neurons in areas
      19, 21, and 20 to different types of visual stimulation in cats with or without
      acute bilateral lesions in areas 17 and 18. Our results showed that, relative to
      the controls, acute lesions inactivated the response of 99.3% of neurons to
      moving gratings and 93% of neurons to flickering square stimuli in areas 19, 21,
      and 20. These results indicated that acute lesions of primary visual areas in
      adult cats may impair most visual abilities. Sparing of vision in cats with
      neonatal lesions in early visual cortical areas may result largely from a
      postoperative reorganization of visual pathways from subcortical nucleus to
      extrastriate visual cortical areas.

PMID- 22467400
TI  - [Glaucoma model for stem cell transplantation research in New Zealand white
      rabbits].
AB  - Glaucoma is a typical irreversible blind neurodegenerative disease for which
      there is no effective treatment for halting visual deterioration. The recent
      development of neural stem cells studies sheds light on a potential resolution
      for this disease. As a result, an appropriate glaucoma modeling method for stem
      cell transplantation study is needed. In the present study, Dexamethasone was
      injected unilaterally into the conjunctiva of New Zealand rabbit at the dose of
      2.5 mg (5 mg/mL), three times a week. After eight weeks, the eye ground
      photography showed that the optic nerve head of the treated eye was expanded, and
      the blood vessel was geniculate compared to the control eye, while the ocular
      media remained transparent. The hematoxylin-eosin (HE) stain of the retinal nerve
      fiber layer (RNFL) sections showed optic neuron death in the treated eye. The
      Heidelberg Retina Tomography (HRT) results showed optic disk morphological
      changes consistent with the pathophysiology of glaucoma in the treated eye,
      including a decrease in the rim area (1.10+/-0.88) mm(2) and mean RNFL thickness
      (0.44+/-0.31) mm, and an increase in the cup/disk ratio 0.17+/-0.13. Then neural
      stem cells were injected into the vitreous body of the treated eye. After five
      months, surviving transplanted cells were observed. These results suggest a
      simple and reproducible chronic glaucoma model, which is appropriate for neural
      stem cell transplant research, has been successfully developed.

PMID- 22467401
TI  - [Locomotor activity and learning and memory abilities in Alzheimer's disease
      induced by aluminum in an acid environment in zebrafish].
AB  - We investigated the contribution of locomotor activity and learning and memory
      abilities to Alzheimer's disease induced by metal neurotoxicity. The metal
      neurotoxicity model was established by using locomotor activity tests and
      activity-avoidance conditioning paradigms, and observing changes in zebrafish
      behaviors after exposure to 50 MUg/L of AlCl(3) with different pH values (pH 7.8,
      pH 6.8 and pH 5.8) for 24 hours and 96 hours. The results showed Alzheimer's
      disease-like behavior in locomotor activity tests and activity-avoidance
      conditioning paradigms by zebrafish receiving AlCl(3) in pH 5.8 significantly
      decreased compared to the control group and groups receiving AlCl(3) in pH 7.8
      and pH 6.8 for 96 hours and 24 hours. These results provide evidences that
      exposure to AlCl( 3) in an acid environment can influence locomotor activity and
      learning and memory abilities in zebrafish. In addition, exposure time and
      concentration of Al induced neurotoxicity and damaged the brain area of memory,
      resulting in Alzheimer's disease-like behavior.

PMID- 22467402
TI  - [Influences of two different training paradigms on spatial learning and memory
      performance of hippocampal injured rats].
AB  - In this study, the 5 d and 7 d training paradigms were adopted to investigate the
      influences of different training procedures on the performance of spatial
      learning and memory of the hippocampal injured rats. The results showed that
      during the hidden-platform acquisition training, similar spatial learning
      dysfunctions were indicated in those two training paradigms. Whereas, when the
      spatial memories have been evaluated, compared with the 5 d training groups, the
      rats under 7 d training procedure not only crossed the platform location less,
      but also preferred to spend less time in the target quadrant.

PMID- 22467403
TI  - Histological grade as an alternative to the Ki67 labeling index is only available
      for luminal-type breast cancers.
AB  - BACKGROUND: The 2011 St. Gallen Consensus Statement advocated using histological
      grade (HG) as a proliferation marker of breast cancer (BC) if reliable Ki67
      labeling index (Ki67-LI) assessment is not available. However, it has been
      difficult to evaluate tumor aggressiveness in case of HG2. METHODS: A total of
      259 cases of BC were assessed for HG, Ki67-LI and other clinicopathological
      features. The cut point for Ki67-LI was interpreted as low and high using a 14%
      threshold. RESULTS: The average age at diagnosis was 58.2 years (range 28-86);
      64.9% of the patients were postmenopausal. Of the 259 cases, 151 were stage I, 78
      were stage II, 29 were stage III, and 1 was stage IV. The subtypes based on
      immunohistochemical staining were 60 cases of luminal A (LA) type (23.2%), 37
      cases of luminal B (LB) (HER2-) type (14.3%), 91 cases of LB (HER2+) type
      (35.1%), 40 cases of human epidermal growth factor receptor 2 (HER2) type (15.4%)
      and 31 cases of triple negative (TN) type (12%). HG was 1 (89 cases, 34.4 %), 2
      (117 cases, 45.2%) and 3 (53 cases, 20.5%). High Ki67-LI cases were observed in
      HG1 (37.1%), HG2 (56.4%) and HG3 (96.2%). Especially in cases of HG2, high Ki67
      LI cases were observed in 0 % of LA type, 100% of LB (HER2-) type, 71.2% of LB
      (HER2+) type, 68.8% of HER2 type and 40.0% of TN type. The average Ki67-LI was
      6.0 +/- 3.8 (LA type), 31.4 +/- 15.7 [LB (HER2-) type], 20.2 +/- 14.8 [LB (HER2+)
      type], 32.7 +/- 21.9 (HER2 type) and 55.7 +/- 32.2 (TN type). All LA-type cases
      and 66.7% of LB (HER2+)-type cases were low Ki67-LI. CONCLUSIONS: Our study
      demonstrates that all LA-type cases and most HG1 of LB (HER2+)-type cases are low
      proliferative. However, HG was not informative enough for estimating tumor
      proliferation in cases of LB (HER2-), HER2 and TN types. It is necessary to add
      other proliferation tools such as the gene expression profiling tool and Ki67-LI
      except in LA and HG1 of LB (HER2+)-type cases.

PMID- 22467404
TI  - The impact of the sentinel node concept on the aesthetic outcome of breast cancer
      conservative surgery.
AB  - BACKGROUND: The sentinel node (SN) concept has brought numerous advantages to
      women with breast cancer. Sparing axillary node anatomy and physiology may
      enhance the cosmetic results of breast cancer conservative surgery, either owing
      to less breast edema or to a better tolerance to the effects of surgery and
      radiotherapy. Our aim was to compare the cosmetic outcome of two randomized
      groups of patients, on a subjective and objective basis. METHODS: A consecutive
      series of breast cancer patients (n = 60) submitted to partial mastectomy plus
      axillary dissection or partial mastectomy plus SN biopsy (included in a
      randomized trial) was photographed. Photos were analysed in three ways: by seven
      different observers according to seven features from poor to excellent; two
      observers estimated the percentage of breast retraction assessment (pBRA); or by
      the BCCT.core 1.0((r)) software. RESULTS: The panel subjective analysis showed a
      benefit in terms of the skin colour for the patients submitted to SN biopsy only.
      This group of patients did not show any advantage in terms of pBRA estimates even
      after the complex BCCT.core appraisal. CONCLUSIONS: The sentinel node concept is
      not associated with improvements in the aesthetic outcome of breast cancer
      conservative treatment.

PMID- 22467405
TI  - Malignant granular cell tumor of the breast: case report and literature review.
AB  - Granular cell tumors (GCTs) are uncommon soft tissue tumors that mostly occur in
      patients between 40 and 60 years of age and can occur at various body sites.
      Malignant granular cell tumors (MGCTs) comprise less than 2 % of GCTs and are
      mostly found on the lower extremities, especially the thighs. These tumors grow
      more rapidly than benign GCTs, and most importantly, they can metastasize. We
      describe an MGCT that presented as a right breast mass in a 79-year-old Japanese
      woman. Local excision was performed for the primary tumor, which was diagnosed as
      an atypical GCT, but 15 months later, the tumor recurred at the same site.
      Thereafter, right mastectomy with axillary lymph node dissection was performed.
      Metastatic disease was identified in 2 of 12 lymph nodes. The pathological
      examination revealed that the tumor had progressed to an MGCT after recurrence.
      Multiple liver, lung and bone metastases were revealed 4 months after the second
      surgery, and the patient died 34 months after the primary surgery. Our findings
      highlighted the difficulty in diagnosing MGCTs using histological features alone
      and suggested the usefulness of Ki67 values. A tumor with a high level of Ki67
      should be treated as malignant, even if the tumor has few pathological features
      of malignancy. 

PMID- 22467406
TI  - Recent advances in research applications of nanophase hydroxyapatite.
AB  - Hydroxyapatite, the main inorganic material in natural bone, has been used widely
      for orthopaedic applications. Due to size effects and surface phenomena at the
      nanoscale, nanophase hydroxyapatite possesses unique properties compared to its
      bulk-phase counterpart. The high surface-to-volume ratio, reactivities, and
      biomimetic morphologies make nano-hydroxyapatite more favourable in applications
      such as orthopaedic implant coating or bone substitute filler. Recently, more
      efforts have been focused on the possibility of combining hydroxyapatite with
      other drugs and materials for multipurpose applications, such as antimicrobial
      treatments, osteoporosis treatments and magnetic manipulation. To build more
      effective nano-hydroxyapatite and composite systems, the particle synthesis
      processes, chemistry, and toxicity have to be thoroughly investigated. In this
      Minireview, we report the recent advances in research regarding nano
      hydroxyapatite. Synthesis routes and a wide range of applications of
      hydroxyapatite nanoparticles will be discussed. The Minireview also addresses
      several challenges concerning the biosafety of the nanoparticles.

PMID- 22467407
TI  - The interaction of plant biotic and abiotic stresses: from genes to the field.
AB  - Plant responses to different stresses are highly complex and involve changes at
      the transcriptome, cellular, and physiological levels. Recent evidence shows that
      plants respond to multiple stresses differently from how they do to individual
      stresses, activating a specific programme of gene expression relating to the
      exact environmental conditions encountered. Rather than being additive, the
      presence of an abiotic stress can have the effect of reducing or enhancing
      susceptibility to a biotic pest or pathogen, and vice versa. This interaction
      between biotic and abiotic stresses is orchestrated by hormone signalling
      pathways that may induce or antagonize one another, in particular that of
      abscisic acid. Specificity in multiple stress responses is further controlled by
      a range of molecular mechanisms that act together in a complex regulatory
      network. Transcription factors, kinase cascades, and reactive oxygen species are
      key components of this cross-talk, as are heat shock factors and small RNAs. This
      review aims to characterize the interaction between biotic and abiotic stress
      responses at a molecular level, focusing on regulatory mechanisms important to
      both pathways. Identifying master regulators that connect both biotic and abiotic
      stress response pathways is fundamental in providing opportunities for developing
      broad-spectrum stress-tolerant crop plants.

PMID- 22467408
TI  - Application of Brachypodium to the genetic improvement of wheat roots.
AB  - To meet the demands of a larger and more affluent global population, wheat yields
      must increase faster this century than last, with less irrigation, fertilizer,
      and land. Modelling and experiments consistently demonstrate a large potential
      for increasing wheat productivity by improving root systems; however, application
      of research to new varieties is slow because of the inherent difficulties
      associated with working underground. This review makes the case for the use of
      the model grass Brachypodium distachyon to simplify root research and accelerate
      the identification of genes underlying wheat root improvement. Brachypodium is a
      small temperate grass with many genomic, genetic, and experimental resources that
      make it a tractable model plant. Brachypodium and wheat have very similar root
      anatomies which are distinct from rice root anatomy that is specialized to help
      it overcome anaerobic conditions associated with submerged roots. As a
      dicotyledonous plant, Arabidopsis has an even more divergent root system that
      features a tap root system and cambia with secondary growth, both of which are
      lacking in the grasses. The major advantage of Brachypodium is its small stature
      that allows the adult grass root system to be readily phenotyped, unlike rice and
      maize. This will facilitate the identification of genes in adult roots that
      greatly influence yield by modulating water uptake during flowering and grain
      development. A summary of the advantages of Brachypodium for root studies is
      presented, including the adult root system architecture and root growth during
      grain development. Routes to translate discoveries from Brachypodium to wheat are
      also discussed.

PMID- 22467410
TI  - A case of undue violent behavior associated with Alzheimer's disease.
AB  - Although dementia is diagnosed by observing cognitive symptoms, noncognitive
      abnormalities are also highly prevalent. Although aggression is a common symptom,
      its presence is usually justifiable by a multitude of externally provoking
      factors. We present a case of Alzheimer's disease with marked unwarranted violent
      behavior.

PMID- 22467411
TI  - The influence of ethnicity and culture on dementia caregiving: a review of
      empirical studies on Chinese Americans.
AB  - The purpose of this article is to pinpoint the cultural and ethnic influences on
      dementia caregiving in Chinese American families through a systemic review and
      analysis of published research findings. Eighteen publications on Chinese
      American dementia family caregivers published in peer-reviewed journals between
      1990 and early 2011 were identified. Based on a systematic database search and
      review process, we found that caregivers' beliefs concerning dementia and the
      concept of family harmony as evidenced through the practice of filial piety are
      permeating cultural values, which together affect attitudes toward research and
      help-seeking behaviors (ie, seeking information on diagnosis and using formal
      services). There is also evidence to suggest that these cultural beliefs impinge
      on key elements of the caregiving process, including caregivers' appraisal of
      stress, coping strategies, and informal and formal support. The study concludes
      with recommendations for future research and practice with the Chinese American
      population.

PMID- 22467412
TI  - Interventions for Hispanic caregivers of patients with dementia: a review of the
      literature.
AB  - BACKGROUND: The number of Hispanics/Latinos living with dementia in the United
      States is expected to rise from 200,000 to 1.3 million by 2050, which will result
      in large numbers of Hispanics/Latinos assuming the role of caregiver. The demands
      of caregiving can negatively impact caregivers' health. The purpose of this
      review was to identify intervention strategies that can help Hispanics/Latinos
      deal with the burden associated with providing care for older adults with
      dementia. METHODS: The authors critically reviewed and analyzed the literature
      for interventions and their relevance to these caregivers. The search engines and
      electronics databases of Google Scholar; Social Gerontology; Health Source:
      Nursing/Academic Edition; MEDLINE; PsycARTICLES; CINAHL; and PubMed, were used to
      locate articles published between 1999 and 2011. RESULTS: Ten intervention
      studies published between 2000 and 2011 were identified that targeted
      Hispanic/Latino caregivers: most were from one clinical trial (REACH).
      DISCUSSION: Future studies should consider culturally tailoring interventions for
      Hispanic/Latino caregivers from differing subcultures, utilizing relevant
      technology in studies, and evaluating the functional level of the care receiver
      and assess where he/she is in the disease process continuum. A better
      understanding of within-group differences among Hispanic/Latino caregivers,
      especially with respect to acculturation, could lead to better tailoring of
      interventions. Future research should consider the possibility of discovery-based
      participatory approaches. Few studies have addressed these areas of concern in
      this population.

PMID- 22467413
TI  - Managing pain to prevent aggression in people with dementia: a nonpharmacologic
      intervention.
AB  - Aggression is a common form of behavioral disturbance in dementia. Strategies to
      prevent and treat aggressive behavior are underdeveloped. However, recent work
      points to several modifiable risk factors that may be targets for intervention.
      Pain management is an evidence-based, feasible, but potentially underused,
      strategy that may be incorporated with other behavioral interventions to prevent
      aggression. In this article, we review areas of overlap in interventions for pain
      and for behavioral disturbances and describe an intervention concept that may
      hold promise for older adults with dementia who are at risk of developing
      aggressive behavior.

PMID- 22467414
TI  - Frailty and quality of life for people with Alzheimer's dementia and mild
      cognitive impairment.
AB  - BACKGROUND: Our aim was to investigate the relationship between frailty and
      health-related quality of life (HR-QOL) in cognitively impaired elderly
      individuals. METHODS: A cross-sectional observational study of a convenience
      sample of 115 patients with a diagnosis of Alzheimer's dementia or mild cognitive
      impairment. Frailty was measured using the biological syndrome model and HR-QOL
      was measured using the DEMQOL-Proxy. Regression models were constructed to
      establish the factors associated with HR-QOL. RESULTS: Frailty and
      neuropsychiatric symptoms were associated with HR-QOL, with Mini-Mental State
      Examination (MMSE) scores >=21 (P = .037, P <= .001, and R (2) = .362).
      Functional limitation was associated with HR-QOL, with MMSE scores <=20 (P = .017
      and R (2) = .377). CONCLUSION: Frailty and neuropsychiatric symptoms were the
      determinants of HR-QOL in the earlier stages of cognitive impairment. Functional
      limitation predicted HR-QOL in the later stages of cognitive impairment. Frailty
      may represent a novel modifiable target in early dementia to improve HR-QOL for
      patients.

PMID- 22467415
TI  - Development of a questionnaire on everyday navigational ability to assess
      topographical disorientation in Alzheimer's disease.
AB  - We developed a Questionnaire on Everyday Navigational Ability (QuENA) to detect
      topographical disorientation (TD) in patients with Alzheimer's disease (PwAD). In
      the QuENA, 3 items were designed to assess landmark agnosia, 2 for egocentric
      disorientation, 3 for heading disorientation, and 2 for inattention. The PwAD and
      their caregivers rated QuENA according to which TD symptoms would occur.
      Regarding the construct validity, confirmatory factor analysis showed that the
      caregiver version of the QuENA fits the proposed TD model well but the patient
      version does not. Regarding the internal consistency, the Cronbach's alpha for
      the caregiver version was 0.91 and that for the patient version was 0.87. A
      discrepancy existed between the appraisal of navigational abilities by PwAD and
      by caregivers, and it was correlated with the number of getting lost (GL) events.
      The caregiver version of QuENA is a feasible, reliable, and valid instrument to
      assess TD and it also discriminates well between the PwAD with GL and those
      without.

PMID- 22467417
TI  - Liposomal formulation increases local delivery of amphotericin from bone cement:
      a pilot study.
AB  - BACKGROUND: Amphotericin is a highly toxic hydrophobic antifungal. Delivery of
      amphotericin from antifungal-loaded bone cement (ALBC) is much lower than would
      be expected for an equivalent load of water-soluble antibacterials. Lipid
      formulations have been developed to decrease amphotericin toxicity. It is unknown
      how lipid formulations affect amphotericin release and compressive strength of
      amphotericin ALBC. QUESTIONS/PURPOSES: We asked if amphotericin release from
      liposomal amphotericin ALBC (1) changed with amphotericin load; (2) differed from
      release from amphotericin deoxycholate ALBC; (3) was an active drug; and (4) if
      liposomal amphotericin affected the bone cement strength. METHODS: Forty-five
      standardized test cylinders were fabricated from three formulations of ALBC:
      SimplexTM P bone cement with 200 mg liposomal amphotericin, 800 mg liposomal
      amphotericin, or 800 mg amphotericin deoxycholate per batch. For each ALBC
      formulation, cumulative released amphotericin was determined from five cylinders,
      and compressive strength was measured for 10 cylinders, five before elution and
      five after. Activity of released amphotericin was determined by growth inhibition
      assay. RESULTS: Amphotericin release was greater for increased load of liposomal
      amphotericin: 770 MUg for 800 mg versus 118 MUg for 200 mg. Amphotericin release
      was greater from liposomal ALBC than from deoxycholate ALBC: 770 MUg versus 23
      MUg over 7 days for 800 mg amphotericin. Released amphotericin was active.
      Compressive strength of liposomal ALBC is decreased, 67 MPa and 34 MPa by Day 7
      in elution for the 200-mg and 800-mg formulations, respectively. CONCLUSIONS:
      Liposomal amphotericin has greater amphotericin release from ALBC than
      amphotericin deoxycholate. Compressive strength of liposomal amphotericin ALBC
      decreases to less than recommended for implant fixation. Local toxicity data are
      needed before liposomal amphotericin ALBC can be used clinically.

PMID- 22467418
TI  - Prolonged bed rest as adjuvant therapy after complex reconstructive spine
      surgery.
AB  - BACKGROUND: The benefits of postoperative mobilization include decreased
      incidence of pulmonary complications, pressure ulcers, and progression of deep
      vein thrombosis. However, the complexity of certain spinal reconstructions and
      the patient's physiologic condition may preclude the possibility of early
      mobilization. Prolonged bed rest after spine surgery is controversial.
      QUESTIONS/PURPOSES: We evaluated the efficacy of prolonged bed rest after complex
      spine surgery to determine (1) patient characteristics that led to prescribing
      bed rest, (2) clinical and radiographic outcomes, (3) complications, and (4)
      estimated direct costs. METHODS: We retrospectively reviewed all 11 patients
      (median age, 50 years) who underwent complex spine surgery followed by prolonged
      bed rest between 2005 and 2010. All patients were deemed at high risk for
      developing pseudarthrosis or instrumentation failure without postoperative bed
      rest. One patient died of complications related to pulmonary tuberculosis at 4
      months. The patients averaged 3 months of bed rest. Minimum followup was 24
      months (median, 30 months; range, 4-52 months). RESULTS: All patients had (1)
      tenuous or limited fixation after correction of severe deformity, (2) previously
      failed spine reconstruction after early mobilization, or (3) limited treatment
      options if failure occurred again. No patient experienced pseudarthrosis, failure
      of instrumentation, thromboembolic disease, pressure ulcers, or pneumonia. One
      patient had a delayed union and one developed late urosepsis. The median cost of
      skilled nursing facilities during the period of bed rest was $16,702, while the
      median cost of home health nursing was $5712. CONCLUSIONS: For patients with
      contraindications to early postoperative mobilization, prolonged bed rest may be
      useful to minimize the risk of complications that can occur with mobilization.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for
      a complete description of levels of evidence.

PMID- 22467420
TI  - Do femoral or salter innominate osteotomies improve femoral head sphericity in
      Legg-Calve-Perthes disease? A meta-analysis.
AB  - BACKGROUND: Recently, the authors of two prospective multicenter observational
      studies recommended surgery to improve head sphericity in older children, whereas
      large retrospective observational studies suggest that surgery does not improve
      head sphericity in older children. Thus, the treatment for Legg-Calve-Perthes
      disease (LCPD) remains controversial. QUESTIONS/PURPOSES: Using a meta-analysis
      we asked whether femoral varus osteotomy (FVO) or Salter innominate osteotomy
      (SIO) resulted in better radiographic head sphericity at the end of the disease
      process as compared with nonsurgical modalities. METHODS: We systematically
      searched the literature using the key concepts LCPD, operative treatment, and
      nonoperative treatment. Of 160 abstracts, 57 full-text studies were reviewed and
      14 papers chosen for meta-analysis. Subgroup analyses were performed to assess
      the impact of age and stage of disease. The odds of a spherical head after
      operative compared with nonoperative treatment were calculated to measure effect
      size for each study and a pooled odds ratio (OR) calculated. RESULTS: Head
      sphericity improved (OR, 1.29; 95% CI, 1.05-1.60) by FVO or SIO as compared with
      patients treated nonoperatively. In children younger than 6 years, it did not
      alter femoral head sphericity (OR, 1.02; 95% CI, 0.45-2.36); children 6 years of
      age and older were more likely to have better femoral head sphericity from
      surgical treatment than nonoperative treatment (OR, 2.05; 95% CI, 1.28-3.26).
      CONCLUSIONS: The data suggest FVO or SIO in patients with LCPD disease who are
      older than 6 years of age during or before the fragmentation phase should be
      considered.

PMID- 22467421
TI  - 50 years ago in CORR: Anterior excision and vertebral body fusion for
      intervertebral disk syndromes of the lower lumbar spine: three- to five-year
      results in 224 cases. Paul H. Harmon, MD, FACS CORR 1963;26:107-127.

PMID- 22467422
TI  - Injuries in overhead athletes: editorial comment.

PMID- 22467423
TI  - Liver progenitor cell interactions with the extracellular matrix.
AB  - Liver progenitor cells (LPCs) are a promising source of cells to treat liver
      disease by cell therapy, due to their capability for self-replication and
      bipotentiality. In order to establish useful culture systems of LPCs and apply
      them to future clinical therapies, it is necessary to understand their
      interactions with their microenvironment and especially with the extracellular
      matrix (ECM). There is considerable evidence from in vivo studies that matrix
      proteins affect the activation, expansion, migration and differentiation of LPCs,
      but the information on the role that specific ECMs play in regulating LPCs in
      vitro is more limited. Nevertheless, current studies suggest that laminin,
      collagen type III, collagen type IV and hyaluronic acid help to maintain the
      undifferentiated phenotype of LPCs and promote their proliferation when cultured
      in media supplemented with growth factors chosen for LPC expansion, whereas
      collagen type I and fibronectin are generally associated with a differentiated
      phenotype under the same conditions. Experimental evidence suggests that
      alpha6beta1 and alpha5beta1 integrins as well as CD44 on the surface of LPCs, and
      their related downstream signals, are important mediators of interactions between
      LPCs and the ECM. The interactions of LPCs with the ECM form the focus of this
      review and the contribution of ECM molecules to strategies for optimizing in
      vitro LPC cultures for therapeutic applications is discussed.

PMID- 22467425
TI  - Synthesis and photocatalytic properties of Cu2S-Pd4S hybrid nanoplates.
AB  - Hex appeal! Cu(2)S-Pd(4)S hybrid nanocrystals with a novel hexagonal nanoplate
      structure were prepared in high yield by a simple one-pot synthetic method (see
      figure). Successful synthesis of this unique structure was achieved through a
      consecutive thermolysis process. The Cu(2)S-Pd(4)S hybrid nanoplates exhibited
      substantially higher photocatalytic activities than pure Cu(2)S nanoplates.

PMID- 22467424
TI  - Development of a novel self-dissolving microneedle array of alendronate, a
      nitrogen-containing bisphosphonate: evaluation of transdermal absorption, safety,
      and pharmacological effects after application in rats.
AB  - Alendronate is a nitrogen-containing bisphosphonate that is widely used for the
      treatment of osteoporosis. In this study, we developed a novel self-dissolving
      micron-size needle array (microneedle array) containing alendronate, which was
      fabricated by micromodeling technologies using hyaluronic acid as a basic
      material. Micron-scale pores in the skin were seen after the application of the
      alendronate-loaded microneedle array, verifying establishment of transdermal
      pathways for alendronate. The absorption of alendronate after the application of
      alendronate-loaded microneedle array was almost equivalent to that after
      subcutaneous administration, and the bioavailability of alendronate was
      approximately 90% in rats. Furthermore, delivery of alendronate via this strategy
      effectively suppressed the decrease in the width of the growth plate in a rat
      model of osteoporosis. Although mild cutaneous irritation was observed after the
      application of the alendronate-loaded microneedle array, it resolved by day 15.
      These findings indicate that this alendronate-loaded microneedle array is a
      promising transdermal formulation for the treatment of osteoporosis.

PMID- 22467427
TI  - Key articles and guidelines in the management of pulmonary arterial hypertension:
      2011 update.
AB  - Pharmacotherapeutic approaches for the management of pulmonary arterial
      hypertension (PAH) have expanded greatly in the last 10 years. Pulmonary arterial
      hypertension is a relatively rare disease and is associated with myriad disease
      processes. The older term for PAH, primary PAH, has been changed to represent
      these differences and to distinguish it from postcapillary PAH associated with
      left-sided heart failure. Limitations in evaluating treatment approaches for PAH
      include its rarity, the small number of patients included in clinical trials, and
      issues regarding the use of placebo-controlled trials in a disease with such a
      high mortality rate if left untreated. Management options include the use of
      prostacyclin and prostacyclin analogues, endothelin receptor antagonists, and
      phosphodiesterase inhibitors, as well as traditional background therapy with
      diuretics, digoxin, calcium channel blockers, and warfarin. Numerous drugs are
      under investigation to evaluate their possible roles in management. Combination
      therapy is increasingly becoming a standard approach to therapy, with mounting
      literature to document effectiveness. Current or emerging roles for the
      pharmacist in the management of PAH largely involves ensuring access to drug
      therapy, facilitating specialty pharmacy dispensing, and providing patient
      counseling. Newer roles may include future drug development, optimized use of
      investigational drugs, and specialized disease management programs. This
      compilation includes a series of articles identifying important literature in
      cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic
      management of pulmonary arterial hypertension (PAH). Most of the cited works
      present the results of significant human clinical studies that have shaped the
      management of patients with PAH. Limited primary literature is available for some
      topics, so in addition, consensus documents prepared by expert panels are
      reviewed. This compilation may serve as a teaching tool, reference resource, or
      update of the literature for pharmacy clinicians, physicians, and students.

PMID- 22467428
TI  - Therapeutic plasma exchange in the elderly: experience at a tertiary center.
AB  - Therapeutic plasma exchange (TPE) is a beneficial albeit complicated method of
      therapy. The elderly, persons 65 years or older are growing in number, with
      increasing need for different therapeutic interventions including TPE. The
      elderly are more likely to have complications and pose challenges when
      considering TPE--both in terms of indications and outcomes. We retrospectively
      investigated the utility of TPE in terms of indications and mortality in the
      elderly (65 and above) versus a younger cohort (18-64 years) between January 1,
      2000 and June 30, 2010. During this period, 581 patients required 4,722 TPE
      treatment sessions. Of them, 185 were elderly (31.8%) requiring 1,289 TPE
      sessions. The indications for TPE were neurological 14.1%, hematological 10.5%,
      renal 6.9%, and miscellaneous 2.0% in the elderly versus 22.7%, 20.8%, 20.7%, and
      4.0% in the younger population undergoing TPE for neurological, hematological,
      renal and miscellaneous indications, respectively. We further investigated the
      mortality within 30 days of admission and a year later. The mortality figures
      within 30 days of admission and a year later in the elderly were 16.2% and 33.5%,
      respectively; higher than in the younger patients; 10.3% and 17.2%, respectively.
      We conclude that TPE is not an uncommon procedure in elderly, with more
      neurological indications, and is associated with higher mortality than younger
      patients.

PMID- 22467429
TI  - Popliteal vascular entrapment syndrome caused by variant lateral head of the
      gastrocnemius muscle leading to pulmonary artery embolism.
AB  - A young man with popliteal vascular entrapment syndrome (PVES) presented with
      arterial occlusion, deep venous thrombosis (DVT), pulmonary artery embolism, and
      pulmonary hypertension. He received computer tomography (CT) and magnetic
      resonance imaging (MRI). Both CT and MRI showed that the left thrombosed
      popliteal vein and artery were entrapped by a variant lateral head of the
      gastrocnemius muscle. The anomalous slip originated from the lateral head of left
      gastrocnemius muscle and ended between the medial and lateral femoral condyles.
      PVES Type V was diagnosed. Compression of the popliteal vein without arterial
      compression can be explained by the more lateral location of the popliteal vein
      relative to the artery and its proximity to the lateral head of the
      gastrocnemius. Compression of the popliteal vein with arterial compression was
      found in this patient. Compression of popliteal vein and artery in this patient
      led to DVT and arterial occlusion. The case was the first reported case
      accompanied by popliteal vein and artery thrombosis caused by variant lateral
      head of the gastrocnemius muscle. Radiologists and doctors should continue to
      look for possible abnormalities in the popliteal fossa in young patients with
      peripheral vascular disease because early diagnosis of PVES allows better choices
      and outcomes of treatment.

PMID- 22467430
TI  - Characterization of thymoquinone binding to human alpha1-acid glycoprotein.
AB  - Thymoquinone (TQ) is the main bioactive component isolated from Nigella sativa
      essential oil and seeds and has been used for the treatment of inflammations,
      liver disorders, arthritis, and is of great importance as a promising therapeutic
      drug for different diseases including cancer. This paper reports the first
      experimental evidence on binding of TQ to human alpha(1)-acid glycoprotein (AGP),
      an important drug-binding glycoprotein in human plasma, which affects
      pharmacokinetic properties of various therapeutic agents. The interaction of TQ
      with AGP has been characterized by Fourier transform infrared (FTIR) and
      fluorescence spectroscopy, as well as by molecular docking experiments. FTIR
      spectroscopy showed that the binding of TQ to AGP slightly increases its thermal
      stability and shifts the existence of a molten globule-like state observed in a
      previous study to higher temperature. The binding constants K(a); the number of
      binding sites n; and the corresponding thermodynamic parameters DeltaG, DeltaH,
      and DeltaS at different temperatures were calculated through fluorescence
      spectroscopy. Fluorescence quenching experiments indicated that TQ binding
      involves hydrophobic interactions and to a lower extent hydrogen bonds, in
      agreement with molecular docking experiments. The data on binding ability of TQ
      to AGP represent basic information for the TQ pharmacokinetics such as drug
      metabolism and distribution in the body.

PMID- 22467431
TI  - One step conversion of wheat straw to sugars by simultaneous ball milling, mild
      acid, and fungus Penicillium simplicissimum treatment.
AB  - Wheat straw is one of the major lignocellulosic plant residues in many countries
      including China. An attractive alternative is the utilization of wheat straw for
      bioethanol production. This article mainly studies a simple one-step wet milling
      with Penicillium simplicissimum and weak acid to hydrolysis of wheat straw. The
      optimal condition for hydrolysis was ball milling 48 h in citrate solvent (pH =
      4) with P. simplicissimum H5 at the speed of 500 rpm and the yield of sugar
      increased with increased milling time. Corresponding structure transformations
      before and after milling analyzed by X-ray diffraction, transmission Fourier
      transform infrared spectroscopy, and environmental scanning electron microscopy
      clearly indicated that this combined treatment could be attributed to the
      crystalline and chemical structure changes of cellulose in wheat straw during
      ball milling. This combined treatment of ball milling, mild acid, and fungus
      hydrolysis enabled the conversion of the wheat straw. Compared with traditional
      method of ball milling, this work showed a more simple, novel, and
      environmentally friendly way in mechanochemical treatment of wheat straw.

PMID- 22467426
TI  - Pericytes on the tumor vasculature: jekyll or hyde?
AB  - The induction of tumor vasculature, known as the 'angiogenic switch', is a rate
      limiting step in tumor progression. Normal blood vessels are composed of two
      distinct cell types: endothelial cells which form the channel through which blood
      flows, and mural cells, the pericytes and smooth muscle cells which serve to
      support and stabilize the endothelium. Most functional studies have focused on
      the responses of endothelial cells to pro-angiogenic stimuli; however, there is
      mounting evidence that the supporting mural cells, particularly pericytes, may
      play key regulatory roles in both promoting vessel growth as well as terminating
      vessel growth to generate a mature, quiescent vasculature. Tumor vessels are
      characterized by numerous structural and functional abnormalities, including
      altered association between endothelial cells and pericytes. These dysfunctional,
      unstable vessels contribute to hypoxia, interstitial fluid pressure, and enhanced
      susceptibility to metastatic invasion. Increasing evidence points to the pericyte
      as a critical regulator of endothelial activation and subsequent vessel
      development, stability, and function. Here we discuss both the stimulatory and
      inhibitory effects of pericytes on the vasculature and the possible utilization
      of vessel normalization as a therapeutic strategy to combat cancer.

PMID- 22467432
TI  - Characteristics of the toxin extracted from liquid culture of Colletotrichum
      capsici f. nicotianae.
AB  - Colletotrichum capsici f. nicotianae is an important plant pathogen in tobacco
      grown area of Weifang region of Shangdong Province, China. In this study, the
      toxicity of liquid culture media from different isolates was characterized, and
      some properties of the toxic ingredient were identified. The results indicated
      that the optimal toxin-producing conditions for C. capsici f. nicotianae were in
      potato dextrose broth under pH 6.0, at 25~30  degrees C for 13 days. The liquid
      culture media from all isolates were toxic to tobacco plants and induced the
      wilting symptoms. The toxin from the liquid culture media has thermal, acid-base
      stability and a broad spectrum of toxicity to the plants. Furthermore, the direct
      bioassay for two components of the liquid filtrates precipitated by ethanol
      showed that the active ingredient of the toxin is a kind of nonprotein substance,
      which was further supported by the papain hydrolysis test.

PMID- 22467433
TI  - Effects of resveratrol on enrichment of adipose-derived stem cells and their
      differentiation to osteoblasts in two-and three-dimensional cultures.
AB  - The goal of this study was to develop a method for increasing the yield of
      multipotent adipose-derived mesenchymal stem cells (ASCs) and osteoprogenitor
      cells (OPCs) from subcutaneous fat. After removing mature adipocytes and
      haematopoietic cells from rat inguinal fat, ASCs in the remaining cell population
      were verified by their attachment to plastic, surface marker profile (CD271(+),
      CD73(+) and CD45(-)) and ability to differentiate into adipocytes, chondrocytes
      and osteoblasts. OPCs were defined as E11(+) and OCN(+). Adherent cells were
      cultured in growth medium (GM) or osteogenic medium (OM) and treated with
      resveratrol (0, 12.5, and 25 uM) for 7 days; ASCs and OPCs were assessed by flow
      cytometry. Osteogenic potential was determined in two-dimensional (2D) cultures
      as a function of alkaline phosphatase-specific activity and osteocalcin
      production. In addition, cells were seeded onto three-dimensional (3D) poly
      epsilon-caprolactone scaffolds and cultured under dynamic conditions;
      mineralization was quantified by micro-CT at 4, 8 and 12 weeks. Resveratrol
      increased the percentage of ASCs in the population (population%) and number of
      ASCs in both GM and OM, but increased only the number of OPCs in GM. In both
      media types resveratrol increased alkaline phosphatase activity and osteocalcin
      levels. In 3D cultures, resveratrol-treated cells significantly increased
      mineralized matrix volume at early time points. Resveratrol exerted a biphasic
      effect on adherent cells by enriching the ASC and OPC populations and enhancing
      osteogenic differentiation. Resveratrol pretreatment induced more mineralization
      at earlier time points and represents a clinically viable technique for
      orthopaedic and dental applications for autologous stem cell therapy.

PMID- 22467434
TI  - Dialysis type may predict carotid intima media thickness and plaque presence in
      end-stage renal disease patients.
AB  - INTRODUCTION: Carotid intima media thickness (CIMT) and carotid plaques (CP) were
      shown to be independent predictors of mortality in end-stage renal disease (ESRD)
      patients. In this study, the authors aimed to compare the two dialysis modalities
      for CIMT and CP presence (CPP). METHODS: ESRD patients who had been on the same
      renal replacement therapy for at least 24 months were selected. CIMT, CPP, known
      risk factors, and laboratory parameters for atherosclerosis were determined for
      each patient. RESULTS: A total of 77 hemodialysis (HD) patients (68% male, 47.6+/
      17.0 years), 61 continuous ambulatory peritoneal dialysis (CAPD) patients (51%
      male, 45.3+/-13.9 years), and 36 age- and sex-matched controls (61% male, 43.3+/
      10.6 years) were included. The mean CIMT (m-CIMT) were 0.99+/-0.24, 0.86+/-0.22,
      and 0.60+/-0.13 mm in the HD, CAPD, and control groups, respectively (HD vs.
      CAPD, P=0.001; HD vs. control, P<0.001; and CAPD vs. control, P<0.001). The CPP
      occurred more frequently in the HD group compared to the CAPD group (64% vs. 39%,
      respectively, P=0.004). The backward linear and logistic regression analysis of
      potential confounders revealed that both m-CIMT and CPP was independently
      associated with dialysis type (beta=0.249, P=0.008; and odds ratio [OR]=4.11, 95%
      CI, 1.72 to 6.73, P=0.015, respectively). CONCLUSION: The authors have shown that
      dialysis type may be an independent predictor of m-CIMT and CPP in long-term ESRD
      patients.

PMID- 22467435
TI  - Arresting mantle formation and redirecting embryonic shell gland tissue by
      platinum2+ leads to body plan modifications in Marisa cornuarietis (Gastropoda,
      Ampullariidae).
AB  - To evaluate the threat that anthropogenic substances pose to animals when they
      are emitted into the environment, tests like the invertebrate embryo toxicity
      test with the ramshorn snail Marisa cornuarietis have been developed. These tests
      are used to investigate substances like the heavy metal platinum (Pt) that is
      used in catalytic converters and is gradually released in car exhausts. In 2010,
      our group reported that high Pt concentrations cause body plan alterations in
      snails and prevent the formation of an external shell during M. cornuarietis
      embryogenesis. Now, this study presents scanning-electron micrographs and
      histological sections of platinum(2+) (Pt(2+))-treated and untreated M.
      cornuarietis embryos and compares "normally" developing and "shell-less" embryos
      during embryogenesis, to reveal the exact course of events that lead to this body
      plan shift. Both groups showed similar development until the onset of torsion 70-
      to 82-h postfertilization. In the Pt(2+)-exposed embryos, the rudimentary shell
      gland (=anlage of both shell gland and mantle, which usually evaginates, grows,
      and eventually covers the visceral sac) does not spread across the visceral sac
      but remains on its ventral side. Without the excessive growth of the shell gland,
      a horizontal rotation of the visceral sac relative to head and foot does not
      occur, as being normal during the process of torsion.

PMID- 22467436
TI  - Ecdysteroid receptor docking suggests that dibenzoylhydrazine-based insecticides
      are devoid of any deleterious effect on the parasitic wasp Psyttalia concolor
      (Hym. Braconidae).
AB  - BACKGROUND: The moulting accelerating compounds (MACs) or ecdysteroid agonists
      represent a selective group of insecticides acting upon binding to the
      ecdysteroid receptor (EcR) and leading to lethal premature moulting in larval
      stages and aborted reproduction in adults. Psyttalia concolor Szepl. is a useful
      parasitic wasp attacking important tephritid pests such as the medfly and olive
      fruit fly. RESULTS: Contact and oral exposure in the laboratory of female
      parasitic wasps to the dibenzoylhydrazine-based methoxyfenozide, tebufenozide and
      RH-5849 did not provoke negative effects. No mortality and no reduction in
      beneficial capacity were observed. The ligand-binding domain (LBD) of the EcR of
      P. concolor was sequenced, and a homology protein model was constructed which
      confirmed a cavity structure with 12 alpha-helices, harbouring the natural insect
      moulting hormone 20-hydroxyecdysone. However, a steric clash occurred for the MAC
      insecticides owing to a restricted extent of the ligand-binding cavity of the
      PcLBD-EcR, while they did dock well in that of susceptible insects. CONCLUSIONS:
      The insect toxicity assays demonstrated that MACs are selective for P. concolor.
      The modelling/docking experiments are indications that these insecticides do not
      bind with the LBD-EcR of P. concolor and support the theory that they show no
      biological effects in the parasitic wasp. These data may help in explaining the
      compatible use of MACs together with parasitic wasps in IPM programmes.

PMID- 22467437
TI  - The ancient Hellenic and Hippocratic origins of head and brain terminology.
AB  - Corpus Hippocraticum, a collection of Hippocratic writings, is considered to be
      the first written monument of rationale medicine. This article focuses on a
      series of ancient Hellenic words which are cited in Hippocratic passages and have
      been adopted in current head and brain terminology either invariably, i.e.,
      keeping their original meaning, or as component parts of newly formed terms. This
      study aims to demonstrate first that the deeper roots of current neuroanatomical
      terminology spread in Hippocratic writings and second, that ancient Hellenic
      remains a living language that would probably ever continue to play a catalytic
      role in the formation of neuroanatomical glossary by providing accurate,
      emblematic, and functional terms.

PMID- 22467438
TI  - Therapeutic apheresis in pediatrics: technique adjustments, indications and
      nonindications, a plasma exchange focus.
AB  - Therapeutic Apheresis procedures are associated with multiple and unique
      challenges in children. The procedures are often performed using evidence or
      experience extrapolated from adult clinical practice, which may not be evidenced
      based. In addition to the clinical challenges, relevant psychological issues,
      modification of protocols and technical hardware are often necessary for safe and
      effective treatment in children. The following review addresses these aspects of
      therapeutic apheresis in children as presented at the Therapeutic Apheresis
      Academy in September 2011. Because of the variety of therapeutic apheresis
      procedures that can be performed in children, for the purposes of this review, an
      emphasis will be on the performance of plasma exchange in children.

PMID- 22467439
TI  - Amaranthus viridis Linn., a common spinach, modulates C-reactive protein, protein
      profile, ceruloplasmin and glycoprotein in experimental induced myocardial
      infarcted rats.
AB  - BACKGROUND: Glycoprotein is one of the components of the cardiac extracellular
      matrix and plays an important role in cardiac remodelling during various cardiac
      diseases, including myocardial infarction (MI). This study was aimed at
      evaluating the preventive role of Amaranthus viridis Linn. on C-reactive protein
      (CRP), total protein, albumin, globulin, ceruloplasmin and glycoproteins in the
      serum and heart of experimental induced myocardial infarcted (MI) rats. RESULTS:
      MI was induced in male Wistar rats by subcutaneous injection of 20 mg kg(-1)
      isoproterenol (ISO) kg(-1) body weight (BW) twice at an interval of 24 h. ISO
      induced MI rats showed a significant increase in the levels of serum CRP and
      ceruloplasmin and a significant decrease in the levels of serum total protein,
      albumin and globulin. Glycoprotein levels in the serum and heart were increased
      in ISO-induced MI rats. Oral administration of 300 mg A. viridis kg(-1) BW day(
      1) for a period of 45 days altered the metabolic derangement in ISO-induced MI
      rats. CONCLUSION: This study exemplifies the protective effect of A. viridis on
      ISO-induced cardiotoxicity in male Wistar rats. The data further reinforce the
      cardioprotective effect of A. viridis by altering CRP and glycoprotein levels.

PMID- 22467440
TI  - Chiral phosphoric acid-catalyzed enantioselective three-component Povarov
      reaction using cyclic enethioureas as dienophiles: stereocontrolled access to
      enantioenriched hexahydropyrroloquinolines.
AB  - Three become one: Phosphoric acid-catalyzed enantioselective three-component
      Povarov reactions of aldehydes, anilines, and endocyclic enethioureas have been
      developed (see scheme). This process afforded hexahydropyrroloquinolines in high
      yields with excellent diastereo- and enantioselectivities. The presence of the
      thiourea functionality is crucial for the enantioselectivity of the reaction.

PMID- 22467441
TI  - Normal left ventricular twist in patients with non-compaction cardiomyopathy, or
      in normal subjects with hypertrabeculation?

PMID- 22467442
TI  - Impaired right and left ventricular diastolic myocardial mechanics and filling in
      asymptomatic children and adolescents after repair of tetralogy of Fallot.
AB  - AIMS: After tetralogy of Fallot (TOF) repair patients have right ventricular (RV)
      dysfunction and reduced exercise tolerance. Diastolic dysfunction may be
      important but is as yet poorly characterized. The early diastolic strain rate
      (SR) is a measure of ventricular relaxation, and may be useful to assess
      diastolic mechanics in TOF. We hypothesized that children after TOF repair have
      diastolic dysfunction and dyssynchrony by this measure, and sought to determine
      their relationship with pulmonary regurgitation (PR), RV enlargement, and aerobic
      exercise capacity. METHODS AND RESULTS: We prospectively recruited asymptomatic
      children after TOF repair. RV and PR volumes were measured by magnetic resonance
      imaging; Doppler and tissue Doppler indices by echocardiography and RV and left
      ventricular (LV) early diastolic SR by two-dimensional speckle tracking. Exercise
      peak oxygen consumption (VO(2)) was determined using bicycle ergometry. Results
      were compared with healthy controls. We studied 53 TOF patients and 49 age
      matched controls. TOF patients had significant PR (2.05 +/- 1 L/m(2)) with
      moderate RV dilatation (157 +/- 39 mL/m(2)), low-normal RV ejection fraction (49
      +/- 8.8%), and moderate QRS prolongation (141 +/- 23 ms). The RV outflow gradient
      was 21.7 +/- 16.0 mmHg. Patients had RV diastolic dysfunction vs. controls
      [reduced tricuspid valve (TV) E/A ratio, E' velocity, and longitudinal diastolic
      SR; increased right atrial volume and TV E/E' ratio]. LV early diastolic radial
      and circumferential SR were lower in TOF patients in association with more PR
      [parameter estimate (PE) 0.177 standard error (SE) (0.08) mL/m(2), P = 0.02] and
      higher RV volumes [(PE) 0.005 (0.002)mL/m(2), P = 0.01]. Diastolic dyssynchrony
      was not different in TOF patients vs. controls. CONCLUSION: TOF patients have RV
      and LV diastolic dysfunction associated with RV enlargement and reduced early
      filling. SR imaging may be useful to quantify early myocardial diastolic
      dysfunction in these children.

PMID- 22467444
TI  - Is there a nonverbal period of development?
AB  - That the infant lives in a nonverbal sensorimotor world is widely believed. Yet
      this notion is being challenged by research, in a range of fields, that depicts
      the young infant as actively attuned to aural speech from birth and able to
      process and use its sounds and meanings well before the end of the first year.
      Following a selective review of the research on infant speech processing between
      birth and age twelve months, three questions are identified that highlight the
      theoretical and clinical implications of this research for psychoanalytic
      conceptualizations of infancy, the nature of language, and clinical process. The
      research, it is concluded, identifies the operation of linguistic and conceptual
      processes in early life, processes that may intersect with the experiential and
      emotional processes with which psychoanalysis is already concerned. Moreover,
      this research raises questions about the view that the nature of infancy is
      essentially nonverbal.

PMID- 22467443
TI  - IL1beta induces mesenchymal stem cells migration and leucocyte chemotaxis through
      NF-kappaB.
AB  - Mesenchymal stem cells are often transplanted into inflammatory environments
      where they are able to survive and modulate host immune responses through a
      poorly understood mechanism. In this paper we analyzed the responses of MSC to IL
      1beta: a representative inflammatory mediator. Microarray analysis of MSC treated
      with IL-1beta revealed that this cytokine activateds a set of genes related to
      biological processes such as cell survival, cell migration, cell adhesion,
      chemokine production, induction of angiogenesis and modulation of the immune
      response. Further more detailed analysis by real-time PCR and functional assays
      revealed that IL-1beta mainly increaseds the production of chemokines such as
      CCL5, CCL20, CXCL1, CXCL3, CXCL5, CXCL6, CXCL10, CXCL11 and CX(3)CL1,
      interleukins IL-6, IL-8, IL23A, IL32, Toll-like receptors TLR2, TLR4, CLDN1,
      metalloproteins MMP1 and MMP3, growth factors CSF2 and TNF-alpha, together with
      adhesion molecules ICAM1 and ICAM4. Functional analysis of MSC proliferation,
      migration and adhesion to extracellular matrix components revealed that IL-1beta
      did not affect proliferation but also served to induce the secretion of trophic
      factors and adhesion to ECM components such as collagen and laminin. IL-1beta
      treatment enhanced the ability of MSC to recruit monocytes and granulocytes in
      vitro. Blockade of NF-kappabeta transcription factor activation with IkappaB
      kinase beta (IKKbeta) shRNA impaired MSC migration, adhesion and leucocyte
      recruitment, induced by IL-1beta demonstrating that NF-kappaB pathway is an
      important downstream regulator of these responses. These findings are relevant to
      understanding the biological responses of MSC to inflammatory environments.

PMID- 22467445
TI  - An operational analysis of the clinical goals of psychoanalytic technique.
AB  - An operational description is presented of the clinical goals of analytic
      technique shared by various analytic orientations. This operational schema of
      their similarities is then used to organize their differences. In this schema,
      analytic schools differ from one another in three areas: the kind of unconscious
      content looked for in uncovering; aspects of the process considered subject to
      direct intervention; and the most effective stance and interventions with which
      to pursue their shared analytic goals. Organizing the differences between
      approaches in the context of shared analytic process goals makes it possible to
      clarify implicit clinical assumptions and to develop empirical rather than
      theoretical clinical discussions between analytic orientations. Understanding the
      intent or purpose of an intervention is useful in comparing approaches, exploring
      clinical controversies, clarifying implicit clinical assumptions, and
      understanding approaches more deeply in their own terms.

PMID- 22467446
TI  - Advances in hemophilia care: report of two symposia at the Hemophilia 2010 World
      Congress.
AB  - The World Federation of Hemophilia (WFH) 2010 World Congress held in Buenos
      Aires, Argentina, in July 2010, attracted more than 4,300 participants from 106
      countries. This report summarizes two symposia held during the congress. The
      first, titled "Emerging Co-Morbidities in the Aging Hemophilia Population:
      Healthcare Challenges and Treatment Opportunities," chaired by Gerry Dolan, MD,
      and Jussara Almeida Cruz, MD, examined the co-morbidities experienced by the
      aging hemophilic patient population, such as cardiovascular disease, cancer,
      arthritis, osteoporosis, hypertension, and obesity. In addition, Bayer's products
      in preclinical and clinical development were reviewed, including a novel factor
      VIIa variant and a long-acting factor VIII molecule, i.e., one that has undergone
      site-specific PEGylation (attachment of polyethylene glycol [PEG] polymer chains
      to another molecule). The other symposium, titled "Practical Steps to Making
      Better Care for Hemophilia Patients a Reality," chaired by Carmen Altisent, MD,
      and Cesar Guerrero, RN, reviewed the steps that hemophilia caregivers can take to
      improve the care of their patients. Issues such as the treatment of hemarthroses,
      the role of the research nurse, and the management of pediatric patients
      transitioning to adulthood were discussed.

PMID- 22467447
TI  - Anatomic study of the superficial sural artery and its implication in the
      neurocutaneous vascularized sural nerve free flap.
AB  - Combined extended nerve and soft tissue defects of the upper extremity require
      nerve reconstruction and adequate soft tissue coverage. This study focuses on the
      reliability of the free vascularized sural nerve graft combined with a
      fasciocutaneous posterior calf flap within this indication. An anatomical study
      was performed on 26 cadaveric lower extremities that had been Thiel fixated and
      color silicone injected. Dissection of the fasciocutaneous posterior calf flap
      involved the medial sural nerve and superficial sural artery (SSA) with its
      septocutaneous perforators, extended laterally to include the lateral cutaneous
      branch of the sural nerve and continued to the popliteal origin of the vascular
      pedicle and the nerves. The vessel and nerves diameter were measured with an
      eyepiece reticle at 4.5* magnification. Length and diameter of the nerves and
      vessels were carefully assessed and reported in the dissection book. A total of
      26 flaps were dissected. The SSA originated from the medial sural artery (13
      cases), the popliteal artery (12 cases), or the lateral sural artery (one case).
      The average size of the SSA was 1.4 +/- 0.4 mm. The mean pedicle length before
      the artery joined the sural nerve was 4.5 +/- 1.9 cm. A comitant vein was present
      in 21 cases with an average diameter of 2.0 +/- 0.8 mm, in 5 cases a separate
      vein needed to be dissected with an average diameter of 3.5 +/- 0.4 mm. The mean
      medial vascularized sural nerve length was 21.2 +/- 8.9 cm. Because of inclusion
      of the vascularized part of the lateral branch of the sural nerve (mean length of
      16.7 +/- 4.8 cm), a total of 35.0 +/- 9.6 cm mean length of vascularized nerve
      could be gained from each extremity. The free vascularized sural nerve graft
      combined with a fasciocutaneous posterior calf flap pedicled on the SSA offers a
      reliable solution for complex tissue and nerve defect.

PMID- 22467449
TI  - Sensitive analysis of metal cations in positive ion mode electrospray ionization
      mass spectrometry using commercial chelating agents and cationic ion-pairing
      reagents.
AB  - Metals play a very important role in many scientific and environmental fields,
      and thus their detection and analysis is of great necessity. A simple and very
      sensitive method has been developed herein for the detection of metals in
      positive ion mode ESI-MS. Metal ions are positively charged, and as such they can
      potentially be detected in positive ion mode ESI-MS; however, their small mass-to
      charge (m/z) ratio makes them fall in the low-mass region of the mass spectrum,
      which has the largest background noise. Therefore, their detection can become
      extremely difficult. A better and well-known way to detect metals by ESI-MS is by
      chelating them with complexation agents. In this study eleven different metals,
      Fe(II), Fe(III), Mg(II), Cu(II), Ru(III), Co(II), Ca(II), Ni(II), Mn(II), Sn(II),
      and Ag(I), were paired with two commercially available chelating agents:
      ethylenediaminetetraacetic acid (EDTA) and ethylenediaminedisuccinic acid (EDDS).
      Since negative ion mode ESI-MS has many disadvantages compared to positive ion
      mode ESI-MS, it would be very beneficial if these negatively charged complex ions
      could be detected in the positive mode. Such a method is described in this paper
      and it is shown to achieve much lower sensitivities. Each of the negatively
      charged metal complexes is paired with six cationic ion-pairing reagents. The new
      positively charged ternary complexes are then analyzed by ESI-MS in the positive
      single ion monitoring (SIM) and single reaction monitoring (SRM) modes. The
      results clearly revealed that the presence of the cationic reagents significantly
      improved the sensitivity for these analytes, often by several orders of
      magnitude. This novel method developed herein for the detection of metals
      improved the limits of detection (LODs) significantly when compared to negative
      ion mode ESI-MS and shows great potential in future trace studies of these and
      many other species.

PMID- 22467448
TI  - The age of cows as a factor shaping the antioxidant level during a nutritional
      experiment with fish oil and linseed supplementation for increasing the
      antioxidant value of milk.
AB  - BACKGROUND: So far, in research studies, the age of cows has not been considered
      as a factor that may influence the changes in the content of milk ingredients
      with antioxidant properties modified by the feed supplementation. The aim of this
      study was to determine the influence of supplementation on the content of
      ingredients having antioxidant properties and to determine the influence of the
      age of cows taking part in the experiment on these changes. The experiment was
      conducted using 20 Polish Holstein Friesian cows, 10 primiparous and 10
      multiparous. The combined supplementation of fish oil and linseed constituted the
      experimental factor. RESULTS: The milk of primiparous cows after 21 days of
      supplementation was characterised by a higher content of C18:1 trans-11, C18:2
      cis-9, trans-11, alpha-retinol, alpha-tocopherol and beta-lactoglobulin compared
      to the milk of multiparous cows, in which a higher level of lactoferrin, C20:5
      and beta-carotene was recorded. In both groups an increase in the total
      antioxidant status was noted (a higher level in the milk of primiparous cows).
      CONCLUSIONS: Modification of the diet of cows with fish oil and linseed
      significantly influenced antioxidant properties of their milk; however, the
      response of multiparous and primaparous cows was noticeably different to the
      supplement introduced.

PMID- 22467450
TI  - Spectral accuracy of a new hybrid quadrupole time-of-flight mass spectrometer:
      application to ranking small molecule elemental compositions.
AB  - RATIONALE: Determining the elemental compositions of unknown molecules is an
      important goal of analytical chemistry. The isotope pattern revealed by a mass
      spectrometer provides valuable information regarding the elemental composition of
      a molecule. In order to employ spectral accuracy considerations for elemental
      composition determination, it is important to know how faithfully a mass
      spectrometer can record the isotope pattern and to understand the magnitude of
      the errors of the relative isotopic abundances. METHODS: Twenty-four small
      molecule drugs and two natural products representing a diverse range of elemental
      compositions and ranging in molecular weight from 236 to 1663 Da were measured on
      a new hybrid orthogonal acceleration quadrupole time-of-flight (Q-TOF) mass
      spectrometer by flow infusion analysis. The similarity between the observed
      profile isotope pattern and the theoretical isotope pattern, denoted spectral
      accuracy, was calculated using a computational algorithm in the program
      MassWorks. RESULTS: The spectral accuracy for all compounds averaged better than
      98%. When using spectral accuracy to rank elemental compositions with the
      elemental constraints (C(1-100)H(0-200)N(0-50)O(0-50)F(0-5)S(0-5)Cl(0-5)Br(0-5))
      further restricted by empirical rules and a mass tolerance <=5 parts-per-million,
      the correct formula was ranked first over 80% of the time. In contrast, when
      using mass accuracy for ranking, only two compounds (8%) were ranked first. For
      quinidine and troglitazone, the initial spectral accuracy measurements were lower
      than expected and further analysis indicated that minor, structurally related
      components were present. CONCLUSIONS: Our work has determined the magnitude of
      spectral accuracy that can be expected on a new Q-TOF mass spectrometer. In
      addition, we demonstrate the utility of spectral accuracy measurements both for
      ranking elemental compositions and also for obtaining insight into the chemical
      nature of the analyte that might otherwise be overlooked.

PMID- 22467451
TI  - Fragmentation of diamide derivatives of 3,4-ethylenedioxythiophene.
AB  - The sequential product ion (MS(n)) fragmentation of four symmetric diamide
      derivatives of 3,4-ethylenedioxythiophene were characterized using ion trap mass
      spectrometry with electrospray ionization and their fragmentation patterns were
      studied. The experimental data consists of mass spectra obtained by tandem mass
      spectrometry, and calculations were obtained by the M06-2X/6-31 G (d,p) method.
      Investigated compounds represent building blocks in synthesis of compounds used
      in different areas of chemistry and industry such as in medicinal chemistry, as
      potential anticancer and anticonvulsant agents, in organic chemistry as linkers
      for solid-phase synthesis, and in the synthesis of a variety of materials in
      polymer chemistry. We present herein the investigation of the fragmentation
      pathway of protonated diamide derivatives of 3,4-ethylenedioxythiophene that
      involves the identification of fragments, influence of proton transfer on
      direction of fragmentation and mechanisms of reactions by which the fragmentation
      process occurs. Data obtained from product ion spectra of these protonated
      compounds and density functional theory (DFT) calculations indicate that the
      fragmentation process takes place via four main reactions: amido-iminol proton
      transfer, reverse cycloaddition, cleavage of the amide bond, and isocyanic acid
      elimination. The 3,4-ethylenedioxythiophene-2,5-dicarboxamide was observed as an
      intermediate in the fragmentation of its alkyl derivatives. To our knowledge,
      this work brings the first correct description of the mechanism of elimination of
      isocyanic acid.

PMID- 22467452
TI  - Matrix-assisted laser desorption/ionization mass spectrometric investigation of
      pollen and their classification by multivariate statistics.
AB  - RATIONALE: A fast and reliable online identification of pollen is not yet
      available. The identification of pollen is based mainly on the evaluation of
      morphological data obtained by microscopic methods. METHODS: Matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI-TOF MS) was applied to the
      analysis of extracts and milled pollen samples. The obtained MALDI data were
      explored for characteristic peak patterns which could be subjected to a
      multivariate statistical analysis. RESULTS: Two sample preparation methods are
      presented, which require only minimal or no chemical extraction of the pollen.
      MALDI pollen spectra could be recorded showing various peak patterns. A
      multivariate statistics approach allowed the classification of pollen into
      clusters indicating similarities and differences between various species.
      CONCLUSIONS: These results demonstrate the potential and the reliability of MALDI
      TOF MS for the identification and, in combination with multivariate statistics,
      also for the classification of pollen.

PMID- 22467453
TI  - Direct analysis in real time mass spectrometry for analysis of sexual assault
      evidence.
AB  - RATIONALE: Sexual assault crimes are vastly underreported and suffer from
      alarmingly low prosecution and conviction rates. The key scientific method to aid
      in prosecution of such cases is forensic DNA analysis, where biological evidence
      such as semen collected using a rape test kit is used to determine a suspect's
      DNA profile. However, the growing awareness by criminals of the importance of DNA
      in the prosecution of sexual assaults has resulted in increased condom use by
      assailants as a means to avoid leaving behind their DNA. Thus, other types of
      trace evidence are important to help corroborate victims' accounts, exonerate the
      innocent, link suspects to the crime, or confirm penetration. METHODS: Direct
      Analysis in Real Time Mass Spectrometry (DART-MS) was employed for the
      comprehensive characterization of non-DNA trace evidence associated with sexual
      assault. The ambient ionization method associated with DART-MS is extremely rapid
      and samples are processed instantaneously, without the need for extraction,
      sample preparation, or other means that might compromise forensic evidence for
      future analyses. RESULTS: In a single assay, we demonstrated the ability to
      identify lubricant formulations associated with sexual assault, such as the
      spermicide nonoxynol-9, compounds used in condom manufacture, and numerous other
      trace components as probative evidence. In addition, the method can also serve to
      identify compounds within trace biological residues, such as fatty acids commonly
      identified in latent fingerprints. CONCLUSIONS: Characterization of lubricant
      residues as probative evidence serves to establish a connection between the
      victim and the perpetrator, and the availability of these details may lead to
      higher rates of prosecution and conviction, as well as more severe penalties. The
      methodology described here opens the way for the adoption of a comprehensive,
      rapid, and sensitive analysis for use in crime labs, while providing knowledge
      that can inform and guide criminal justice policy and practice.

PMID- 22467454
TI  - Expanding the data depth for the analysis of complex crude oil samples by Fourier
      transform ion cyclotron resonance mass spectrometry using the spectral stitching
      method.
AB  - RATIONALE: Crude oil samples are very complex mixtures of compounds and only
      Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) provides
      the ultra-high mass resolution necessary to resolve them. However, FT-ICR MS
      operates best when only a small amount of ions is present during each transient.
      This cannot be accomplished with crude oil samples without chromatography because
      more than 50,000 compounds can be present, with the result that species with low
      intensity may be suppressed and are detected either with low intensity or not at
      all. METHODS: Spectral stitching was used to overcome the problems associated
      with suppression effects, where only short mass windows of 30 amu were scanned to
      reduce the amount of ions present in each individual scan. Afterwards, all the
      scans were co-added and the subsequent spectrum was used to calculate individual
      class distributions. RESULTS: A heavy crude oil sample was analyzed using
      spectral stitching and this approach was compared with analysis using a broadband
      method in order to illustrate the enhancement in depth of information. Although
      both methods took the same analysis time a seven-times increase in the number of
      detected species was observed when the spectral stitching method was used
      compared with the commonly applied broadband method in a 900 amu mass window.
      CONCLUSIONS: Spectral stitching using smaller selected ion monitoring (SIM)
      windows for complex crude oil samples allows better class distribution to be
      obtained because less ion suppression is observed.

PMID- 22467455
TI  - Gas chromatography/isotope ratio mass spectrometry of recalcitrant target
      compounds: performance of different combustion reactors and strategies for
      standardization.
AB  - RATIONALE: Compound-specific isotope analysis (CSIA) relies on continuous flow
      combustion of organic substances to CO(2) and N(2) in a miniature reactor to
      measure (13)C/(12)C and (15)N/(14) N stable isotope ratios. Accurate analysis is
      well established for many volatile hydrocarbons. In contrast, compounds which
      contain hetero and halogen atoms are less volatile and may be more recalcitrant
      to combustion. METHODS: This study tested carbon and nitrogen isotope analysis of
      atrazine, desethylatrazine (DEA), dichlobenil and 2,6-dichlorobenzamide (BAM) by
      gas chromatography/isotope ratio mass spectrometry (GC/IRMS) with multiple
      reactor tubes of two different kinds (conventional CuO/NiO/Pt and a NiO tube/CuO
      NiO reactor prototype). RESULTS: The advantages of the NiO tube/CuO-NiO reactor
      were the absence of an additional reduction reactor, the possibility of routine
      reoxidation in nitrogen isotope analysis, and reliable atrazine and DEA
      measurements over several hundred injections. In contrast, BAM analysis showed
      good accuracy for carbon, but notable variations in the trueness of nitrogen
      isotope ratios. Accurate carbon and nitrogen analysis was nevertheless possible
      by bracketing samples with external compound-specific standards and subsequent
      offset correction. CONCLUSIONS: We conclude that instrument data should never be
      taken at its 'face value', but must consistently be validated with compound
      specific standards of the respective analytes.

PMID- 22467456
TI  - Gas-phase reactivity of protonated 2-oxazoline derivatives: mass spectrometry and
      computational studies.
AB  - RATIONALE: Oxazolines have attracted the attention of researchers worldwide due
      to their versatility as carboxylic acid protecting groups, chiral auxiliaries,
      and ligands for asymmetric catalysis. Electrospray ionization tandem mass
      spectrometric (ESI-MS/MS) analysis of five 2-oxazoline derivatives has been
      conducted, in order to understand the influence of the side chain on the gas
      phase dissociation of these protonated compounds under collision-induced
      dissociation (CID) conditions. METHODS: Mass spectrometric analyses were
      conducted in a quadrupole time-of-flight (Q-TOF) spectrometer fitted with
      electrospray ionization source. Protonation sites have been proposed on the basis
      of the gas-phase basicity, proton affinity, atomic charges, and a molecular
      electrostatic potential map obtained on the basis of the quantum chemistry
      calculations at the B3LYP/6-31 + G(d,p) and G2(MP2) levels. RESULTS: Analysis of
      the atomic charges, gas-phase basicity and proton affinities values indicates
      that the nitrogen atom is a possible proton acceptor site. On the basis of these
      results, two main fragmentation processes have been suggested: one taking place
      via neutral elimination of the oxazoline moiety (99 u) and another occurring by
      sequential elimination of neutral fragments with 72 u and 27 u. These processes
      should lead to formation of R(+). CONCLUSIONS: The ESI-MS/MS experiments have
      shown that the side chain could affect the dissociation mechanism of protonated 2
      oxazoline derivatives. For the compound that exhibits a hydroxyl at the lateral
      chain, water loss has been suggested to happen through an E2-type elimination, in
      an exothermic step.

PMID- 22467457
TI  - Probing the mechanism and dynamic reversibility of trianglimine formation using
      real-time electrospray ionization time-of-flight mass spectrometry.
AB  - RATIONALE: The [3+3]-cyclocondensation reactions of chiral (1R,2R)-1,2
      diaminocyclohexane with aromatic or aliphatic bis-aldehydes to form trianglimine
      macrocycles were reported a decade ago and were believed to proceed through a
      stepwise mechanistic pathway; however, no intermediates were ever isolated or
      detected and characterized. METHODS: We investigated the mechanism of the [3+3]
      cyclocondensation reaction using a selection of dialdehyde starting materials
      using real-time electrospray ionization time-of-flight mass spectrometry.
      RESULTS: We observed up to a maximum of 16 reaction intermediates along the
      reaction pathway, more than for any other multistep reaction reported. We also
      probed the dynamic reversibility of trianglimines using selected small dynamic
      combinatorial libraries and showed that trianglimine formation is indeed fully
      reversible. CONCLUSIONS: This study represents a significant contribution towards
      understanding the mechanism of trianglimine formation and its potential
      applicability can be extended to include other cascade reactions.

PMID- 22467458
TI  - Accuracy of relative isotopic abundance and mass measurements in a single-stage
      orbitrap mass spectrometer.
AB  - Orbitrap technology offers a combination of different technical specifications
      which have not yet been achieved by other high-resolution mass spectrometry
      instrumentation. This refers to the combination of sensitivity, dynamic range,
      mass accuracy, resolution and speed. The high stability of the mass axis and the
      general ease of use made the orbitrap instrumentation attractive for routine
      laboratories. However, there are circumstances where significantly deviating
      relative isotopic abundance (RIA) and shifting accurate masses can be observed.
      RIA becomes biased at low ion counts. Furthermore, two adjacent, only partially
      resolved near-isobaric ions are detected with a deviating RIA. The presence of a
      very intensive mass peak does not only induce Fourier transformation related
      artefacts (side-lobes) but can cause mass shifts of small adjacent near-isobaric
      mass peaks. These effects are not as drastic as known for Fourier transform ion
      cyclotron resonance instruments. Still, users trying to identify or quantify
      trace level compounds should be aware about such limitations in order to avoid
      possible pitfalls.

PMID- 22467459
TI  - Identification of pesticide transformation products in agricultural soils using
      liquid chromatography/quadrupole-time-of-flight mass spectrometry.
AB  - RATIONALE: A study of pesticide transformation products (TPs) was carried out in
      soils of agricultural areas working under integrated pest management programs
      (IPMs). Bupirimate and cyromazine were the pesticides detected in soils after an
      initial pre-screening. The aim of this work was the identification of relevant
      TPs of these two pesticides. METHODS: Soil samples were extracted by pressurized
      liquid extraction (PLE), using a mixture of ethyl acetate/methanol (3:1, v/v),
      and analyzed by ultra-high-pressure liquid chromatography coupled to hybrid
      quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS). For confirmation
      purposes, tandem mass spectrometry (MS(2) ) experiments were carried out using
      QTOF-MS, obtaining specific fragment structures of the pesticides and their
      degradates. RESULTS: Retention times and exact masses of the protonated molecules
      were used for the identification of the pesticides bupirimate (m/z 317.1642) and
      cyromazine (m/z 167.1040) and their respective TPs, namely ethirimol (m/z
      210.1601) and melamine (m/z 127.0727). A novel strategy using pseudo-MS(3)
      experiments was developed to confirm the structure of bupirimate TP (ethirimol).
      This strategy consists of generating the particular TP in the ion source, via
      collision-induced fragmentation, and then performing MS/MS to the fragment ion
      formed in-source. CONCLUSIONS: Ethirimol and melamine were identified as
      degradation products of bupirimate and cyromazine, respectively. The study was
      applied to the analysis of 15 agricultural soil samples finding bupirimate and
      ethirimol in seven samples, cyromazine in one sample and melamine in four
      samples.

PMID- 22467460
TI  - Laser ablation synthesis of new gold phosphides using red phosphorus and nanogold
      as precursors. Laser desorption ionisation time-of-flight mass spectrometry.
AB  - Gold phosphides show unique optical or semiconductor properties and there are
      extensive high technology applications, e.g. in laser diodes, etc. In spite of
      the various AuP structures known, the search for new materials is wide. Laser
      ablation synthesis is a promising screening and synthetic method. Generation of
      gold phosphides via laser ablation of red phosphorus and nanogold mixtures was
      studied using laser desorption ionisation time-of-flight mass spectrometry (LDI
      TOFMS). Gold clusters Au(m)(+) (m = 1 to ~35) were observed with a difference of
      one gold atom and their intensities were in decreasing order with respect to m.
      For P(n)(+) (n = 2 to ~111) clusters, the intensities of odd-numbered phosphorus
      clusters are much higher than those for even-numbered phosphorus clusters. During
      ablation of P-nanogold mixtures, clusters Au(m)(+) (m = 1-12), P(n)(+) (n = 2-7,
      9, 11, 13-33, 35-95 (odd numbers)), AuP(n)(+) (n = 1, 2-88 (even numbers)),
      Au(2)P(n)(+) (n = 1-7, 14-16, 21-51 (odd numbers)), Au(3)P(n)(+) (n = 1-6, 8, 9,
      14), Au(4)P(n)(+) (n = 1-9, 14-16), Au(5)P(n)(+) (n = 1-6, 14, 16), Au(6)P(n)(+)
      (n = 1-6), Au(7)P(n)(+) (n = 1-7), Au(8)P(n)(+) (n = 1-6, 8), Au(9)P(n)(+) (n = 1
      10), Au(10)P(n)(+) (n = 1-8, 15), Au(11)P(n)(+) (n = 1-6), and Au(12)P(n)(+) (n =
      1, 2, 4) were detected in positive ion mode. In negative ion mode, Au(m)(-) (m =
      1-5), P(n)(-) (n = 2, 3, 5-11, 13-19, 21-35, 39, 41, 47, 49, 55 (odd numbers)),
      AuP(n)(-) (n = 4-6, 8-26, 30-36 (even numbers), 48), Au(2)P(n)(-) (n = 2-5, 8,
      11, 13, 15, 17), A(3) P(n)(-) (n = 6-11, 32), Au(4)P(n)(-) (n = 1, 2, 4, 6, 10),
      Au(6)P(5)(-), and Au(7)P(8)(-) clusters were observed. In both modes, phosphorus
      rich Au(m)P(n) clusters prevailed. The first experimental evidence for formation
      of AuP(60) and gold-covered phosphorus Au(12)P(n) (n = 1, 2, 4) clusters is
      given. The new gold phosphides generated might inspire synthesis of new Au-P
      materials with specific properties.

PMID- 22467461
TI  - Rapid identification of synthetic cannabinoids in herbal samples via direct
      analysis in real time mass spectrometry.
AB  - RATIONALE: Dozens of synthetic cannabinoid analogs purposefully meant to
      circumvent legal restrictions associated with controlled substances continue to
      be manufactured and promoted as producing 'legal highs'. These designer drugs are
      difficult to identify in conventional drug screens not only because routine
      protocols have not been developed for their detection, but also because their
      association with complex plant matrices during manufacture generally requires
      labor-intensive extraction and sample preparation for analysis. To address this
      new and important challenge in forensic chemistry, Direct Analysis in Real Time
      Mass Spectrometry (DART-MS) is applied to the analysis of these designer drugs.
      METHODS: DART-MS was employed to sample synthetic cannabinoids directly on
      botanical matrices. The ambient ionization method associated with DART-MS
      permitted the analysis of solid herbal samples directly, without the need for
      extraction or sample preparation. The high mass resolution time-of-flight
      analyzer allowed identification of these substances despite their presence within
      a complex matrix and enabled differentiation of closely related analogs. RESULTS:
      DART-MS was performed to rapidly identify the synthetic cannabinoids AM-251 and
      JWH-015. For each cannabinoid, three hundred micrograms (300 ug) of material was
      easily detected within an excess of background matrix by mass. CONCLUSIONS: New
      variations of herbal blends containing a wide range of base components and laced
      with synthetic cannabinoids are being produced, making their presence difficult
      to track by conventional methods. DART-MS permits rapid identification of trace
      synthetic cannabinoids within complex biological matrices, with excellent
      sensitivity and specificity compared with standard methods.

PMID- 22467462
TI  - Novel product ions of 2-aminoanilide and benzimidazole Ag(I) complexes using
      electrospray ionization with multi-stage tandem mass spectrometry.
AB  - RATIONALE: The 2-aminoaniline scaffold is of significant value to the
      pharmaceutical industry and is embedded in a number of pharmacophores including 2
      aminoanilides and benzimidazoles. A novel application of coordination ion spray
      mass spectrometry (CIS-MS) for interrogating the silver ion (Ag(+)) complexes of
      a homologous series of these compounds using multi-stage tandem mass spectrometry
      is described. Unlike the ubiquitous alkali metal ion complexes, Ag(+) complexes
      of 2-aminoanilides and benzimidazoles were found to yield [M - H](+) ions in
      significant abundance via gas-phase elimination of the metal hydride (AgH)
      resulting in unique product ion cascades. METHODS: Sample introduction was by
      liquid chromatography with mass spectrometry analysis performed on a hybrid
      linear ion trap/orbitrap instrument capable of high-resolution measurements.
      RESULTS: Rigorous structural characterization by multi-stage tandem mass
      spectrometry using [M +  H](+), [M - H](-) and [M - H](+) precursor ions derived
      from ESI and CIS experiments was performed for the homologous series of 2
      aminoanilide and benzimidazole compounds. A full tabular comparison of structural
      information resulting from these product ion cascades was produced. CONCLUSIONS:
      Multi-stage tandem mass spectrometry of [M - H](+) ions resulting from Ag(+)
      complexes of 2-aminoanilides and benzimidazoles in CIS-MS experiments produced
      unique product ion cascades that exhibited complementary structural information
      to that obtained from tandem mass spectrometry of [M  +  H](+) and [M - H](-)
      ions by electrospray ionization (ESI). These observations may be broadly
      applicable to other compounds that are observed to form Ag(+) complexes and
      eliminate AgH.

PMID- 22467463
TI  - Study of the mass spectrometric behaviors of anthocyanins in negative ionization
      mode and its applications for characterization of anthocyanins and non
      anthocyanin polyphenols.
AB  - RATIONALE: Traditionally, anthocyanin analysis in mass spectrometry is carried
      out in the positive ionization mode only. A study of the mass spectrometric
      behaviors of anthocyanins in the negative ionization mode revealed interesting
      characteristics that was not previously reported. It can be used to differentiate
      anthocyanins from other non-anthocyanin polyphenols. METHODS: An ultra-high
      performance liquid chromatography with high-resolution mass spectrometry (U
      HPLC/HRMS) method was developed. The method used multiple-stage mass
      fragmentation in both the negative and positive ion modes. The whole cycle time
      of the new method is 1.8 s for two full scans and six data-dependent scans.
      RESULTS: The new strategy found, in the negative ionization mode, a series of
      characteristic ions, e.g. [M-2H](-), [M-2H  +  H(2)O](-), formic acid adducts,
      and doubly charged ions were observed for the MS analysis of anthocyanins. The
      characteristic ions can be used for identification and differentiation of
      anthocyanins and non-anthocyanin phenolic compounds. Comprehensive studies were
      performed on the differentiation of anthocyanins and non-anthocyanin polyphenols
      in blueberry (Vaccinium cyanococcus), Hongcaitai (Brassica compestris L. var.
      purpurea Bailey), and red radish (Raphanus sativus var. longipinnatus
      'Shinrimei'). CONCLUSIONS: The data generated from a single LC run enables rapid
      and reliable differentiation and identification of anthocyanins and non
      anthocyanins in botanicals and foods. Published 2012. This article is a US
      Government work and is in the public domain in the USA.

PMID- 22467464
TI  - A liquid chromatography/tandem mass spectrometry method for measuring the in vivo
      incorporation of plasma free fatty acids into intramyocellular ceramides in
      humans.
AB  - RATIONALE: Sphingolipids are important components of cell membranes that serve as
      cell signaling molecules; ceramide plays a central role in sphingolipid
      metabolism. De novo ceramide biosynthesis depends on fatty acid availability, but
      whether muscle uses circulating free fatty acids or pre-existing intracellular
      stores is unknown. Our goal was to develop a method to detect the incorporation
      of intravenously infused [U-(13)C]palmitate into intramyocellular ceramides.
      METHODS: We used liquid chromatography/tandem mass spectrometry (LC/MS/MS) to
      measure the concentrations of different sphingolipid species and (13)C-isotopic
      enrichment of 16:0-ceramide. Chromatographic separation was performed using ultra
      performance liquid chromatography. The analysis was performed on a triple
      quadrupole mass spectrometer using a positive ion electrospray ionization source
      with selected reaction monitoring (SRM). RESULTS: The sphingolipids ions, except
      enriched ceramide, were monitored as [M+2+H](+). The [(13)C(16)]16:0-ceramide was
      monitored as [M+16+H](+). By monitoring two different transitions of the
      [(13)C(16)]16:0-ceramide (554/536 and 554/264) we could indirectly measure
      enrichment of the palmitate that is not a part of the sphingoid base.
      Concentration and enrichment could be measured using 20 mg of muscle obtained
      from volunteers receiving a low dose [U-(13)C]palmitate infusion. CONCLUSIONS:
      LC/MS/MS can be used to detect the incorporation of plasma palmitate into muscle
      ceramides in humans, in vivo.

PMID- 22467465
TI  - High-resolution matrix-assisted laser desorption/ionization imaging of tryptic
      peptides from tissue.
AB  - RATIONALE: The analysis of proteins by mass spectrometry imaging is an important
      biomedical application as spatial distributions can be used to identify markers
      for pathological processes. The direct detection and identification of proteins
      on tissue can be hindered by a number of factors including limited mass range and
      fragmentation efficiency as well as incompatibility with formalin-fixed samples.
      METHODS: To overcome some of these limitations, on-tissue digestion of proteins
      was followed by detection of the resulting peptides. Trypsin was applied by a
      spraying device. Matrix-assisted laser desorption/ionization (MALDI) imaging
      experiments were performed with a home-built atmospheric-pressure imaging source
      attached to a LTQ Orbitrap mass spectrometer. The mass accuracy under imaging
      conditions was better than 3 ppm RMS. This allowed for confident identification
      of tryptic peptides by comparison with liquid chromatography/electrospray
      ionization tandem mass spectrometry (LC/ESI-MS/MS) measurements of an adjacent
      mouse brain section. RESULTS: A spatial resolution of 50 um was obtained for
      tryptic peptides on tissue. Several tryptic peptides of myelin showed matching
      spatial distributions, and numerous tryptic peptides of other proteins were
      identified. MS images were generated with a bin size (mass range used for image
      generation) of Deltam/z = 0.01 u. Examples demonstrate that MS images with lower
      selectivity can result in misleading information about the spatial distribution
      of tryptic peptides. CONCLUSIONS: The presented method combines a significantly
      improved spatial resolution for tryptic peptides with low-ppm mass accuracy in a
      single experiment and thus provides highly reliable and specific information.

PMID- 22467467
TI  - Simultaneous measurements of gas isotopic compositions of fluid inclusion gases
      (N2, CH4, CO2) using continuous-flow isotope ratio mass spectrometry.

PMID- 22467466
TI  - Analysis of select Dalbergia and trade timber using direct analysis in real time
      and time-of-flight mass spectrometry for CITES enforcement.
AB  - RATIONALE: International trade of several Dalbergia wood species is regulated by
      The Convention on International Trade in Endangered Species of Wild Fauna and
      Flora (CITES). In order to supplement morphological identification of these
      species, a rapid chemical method of analysis was developed. METHODS: Using Direct
      Analysis in Real Time (DART) ionization coupled with Time-of-Flight (TOF) Mass
      Spectrometry (MS), selected Dalbergia and common trade species were analyzed.
      Each of the 13 wood species was classified using principal component analysis and
      linear discriminant analysis (LDA). These statistical data clusters served as
      reliable anchors for species identification of unknowns. RESULTS: Analysis of 20
      or more samples from the 13 species studied in this research indicates that the
      DART-TOFMS results are reproducible. Statistical analysis of the most abundant
      ions gave good classifications that were useful for identifying unknown wood
      samples. CONCLUSIONS: DART-TOFMS and LDA analysis of 13 species of selected
      timber samples and the statistical classification allowed for the correct
      assignment of unknown wood samples. This method is rapid and can be useful when
      anatomical identification is difficult but needed in order to support CITES
      enforcement. Published 2012. This article is a US Government work and is in the
      public domain in the USA.

PMID- 22467468
TI  - Sturgeons, sharks, and rays have multifocal crystalline lenses and similar lens
      suspension apparatuses.
AB  - Crystalline lenses with multiple focal lengths in monochromatic light (multifocal
      lenses) are present in many vertebrate groups. These lenses compensate for
      chromatic aberration and create well-focused color images. Stabilization of the
      lens within the eye and the ability to adjust focus are further requirements for
      vision in high detail. We investigated the occurrence of multifocal lenses by
      photorefractometry and lens suspension structures by light and electron
      microscopy in sturgeons (Acipenseriformes, Chondrostei) as well as sharks and
      rays (Elasmobranchii, Chondrichthyes). Multifocal lenses were found in two more
      major vertebrate groups, the Chondrostei represented by Acipenseriformes and
      Chondrichthyes represented by Elasmobranchii. The lens suspension structures of
      sturgeons, sharks, and rays are more complex than described previously. The lens
      is suspended by many delicate suspensory fibers in association with a ventral
      papilla in all groups studied. The arrangements of the suspensory fibers are most
      similar between sturgeons and sharks. In rays, the lens is suspended by a smaller
      ventral papilla and the suspensory fibers are arranged more concentrically to the
      lens.

PMID- 22467469
TI  - Muscles that do not cross the knee contribute to the knee adduction moment and
      tibiofemoral compartment loading during gait.
AB  - The aims of this study were to evaluate and explain the individual muscle
      contributions to the medial and lateral knee compartment forces during gait, and
      to determine whether these quantities could be inferred from their contributions
      to the external knee adduction moment. Gait data from eight healthy male subjects
      were used to compute each individual muscle contribution to the external knee
      adduction moment, the net tibiofemoral joint reaction force, and reaction moment.
      The individual muscle contributions to the medial and lateral compartment forces
      were then found using a least-squares approach. While knee-spanning muscles were
      the primary contributors, non-knee-spanning muscles (e.g., the gluteus medius)
      also contributed substantially to the medial compartment compressive force.
      Furthermore, knee-spanning muscles tended to compress both compartments, while
      most non-knee-spanning muscles tended to compress the medial compartment but
      unload the lateral compartment. Muscle contributions to the external knee
      adduction moment, particularly those from knee-spanning muscles, did not
      accurately reflect their tendencies to compress or unload the medial compartment.
      This finding may further explain why gait modifications may reduce the knee
      adduction moment without necessarily decreasing the medial compartment force.

PMID- 22467470
TI  - A novel approach to human cranial tissue regeneration and frontal sinus
      obliteration with an autogenous platelet-rich/fibrin-rich composite matrix: 10
      patients with a 6-10 year follow-up.
AB  - Advanced frontal sinus disease non-responsive to conservative therapy has been
      treated with fat obliteration for decades. More recently, a wide variety of
      autogenous, allogenic or synthetic materials have also been used. In this study
      we present a treatment based on totally autogenous procedures and materials that
      was successfully implemented in 10 patients and followed up for a period of 6-10
      years, to evaluate the feasibility of a new approach for the treatment of frontal
      sinus disease and other related cranial osseous derangements, based on
      regenerative medicine as an alternative to fat or other obliterating or grafting
      materials. Platelet-rich and -poor plasma (PRP, PPP) are set to clot with
      cortical shavings from the skull surface. After surgically stimulating the sinus
      to encourage cell chemotaxis, migration and homing, the bioactive scaffold is
      placed and covered with a PPP membrane and a periosteal flap. Ten patients with
      pathologies ranging from devastating infection to invasive tumours or trauma were
      treated with this regenerative procedure in a single-stage surgery. All patients
      had an uneventful recovery with bone formation and no complications or
      recurrences over the years. The application of modern principles in tissue
      regeneration and wound healing has resulted in a favourable outcome, with no
      complications or sequelae, in a series of 10 patients with advanced frontal sinus
      disease over a long period of time.

PMID- 22467471
TI  - Information-theoretic approach for automated white matter fiber tracts
      reconstruction.
AB  - Fiber tracking is the most popular technique for creating white matter
      connectivity maps from diffusion tensor imaging (DTI). This approach requires a
      seeding process which is challenging because it is not clear how and where the
      seeds have to be placed. On the other hand, to enhance the interpretation of
      fiber maps, segmentation and clustering techniques are applied to organize fibers
      into anatomical structures. In this paper, we propose a new approach to
      automatically obtain bundles of fibers grouped into anatomical regions. This
      method applies an information-theoretic split-and-merge algorithm that considers
      fractional anisotropy and fiber orientation information to automatically segment
      white matter into volumes of interest (VOIs) of similar FA and eigenvector
      orientation. For each VOI, a number of planes and seeds is automatically placed
      in order to create the fiber bundles. The proposed approach avoids the need for
      the user to define seeding or selection regions. The whole process requires less
      than a minute and minimal user interaction. The agreement between the automated
      and manual approaches has been measured for 10 tracts in a DTI brain atlas and
      found to be almost perfect (kappa > 0.8) and substantial (kappa > 0.6). This
      method has also been evaluated on real DTI data considering 5 tracts. Agreement
      was substantial (kappa > 0.6) in most of the cases.

PMID- 22467473
TI  - Dyspnea in a patient with Raynaud's phenomenon: the uncovering of interstitial
      lung disease.
AB  - Interstitial lung disease (ILD) can develop in patients with connective tissue
      disease (CTD) in the context of progressive multiorgan involvement, but ILD can
      also be the predominant manifestation of active CTD. A high index of suspicion
      for CTD in patients presenting with pulmonary disease might facilitate timely,
      accurate diagnosis and management.

PMID- 22467472
TI  - No evidence that major mtDNA European haplogroups confer risk to schizophrenia.
AB  - Previous studies suggest that genetic factors could be involved in mitochondrial
      dysfunction observed in schizophrenia (SZ), some of them claiming a role of mtDNA
      common variants (mtSNPs) and/or haplogroups (hgs) in developing this disorder.
      These studies, however, have mainly been undertaken on relatively small cohorts
      of patients and control individuals and most have not yet been replicated. To
      further analyze the role of mtSNPs in SZ risk, we have carried out the largest
      genotyping effort to date using two Spanish case-control samples comprising a
      total of 942 schizophrenic patients and 1,231 unrelated controls: 454 patients
      and 616 controls from Santiago de Compostela (Galicia) and 488 patients and 615
      controls from Reus (Catalonia). A set of 25 mtSNPs representing main branches of
      the European mtDNA phylogeny were genotyped in the Galician cohort and a subset
      of 16 out of these 25 mtSNPs was genotyped in the Catalan cohort. These 16 common
      variants characterize the most common European branches of the mtDNA phylogeny.
      We did not observe any positive association of mtSNPs and hgs with SZ. We discuss
      several deficiencies of previous studies that might explain the false positive
      nature of previous findings, including the confounding effect of population sub
      structure and deficient statistical methodologies. It is unlikely that mtSNPs
      defining the most common European mtDNA haplogroups are related to SZ.

PMID- 22467474
TI  - Neural stem cells directly differentiated from partially reprogrammed fibroblasts
      rapidly acquire gliogenic competency.
AB  - Neural stem cells (NSCs) were directly induced from mouse fibroblasts using four
      reprogramming factors (Oct4, Sox2, Klf4, and cMyc) without the clonal isolation
      of induced pluripotent stem cells (iPSCs). These NSCs gave rise to both neurons
      and glial cells even at early passages, while early NSCs derived from clonal
      embryonic stem cells (ESCs)/iPSCs differentiated mainly into neurons. Epidermal
      growth factor-dependent neurosphere cultivation efficiently propagated these
      gliogenic NSCs and eliminated residual pluripotent cells that could form
      teratomas in vivo. We concluded that these directly induced NSCs were derived
      from partially reprogrammed cells, because dissociated ESCs/iPSCs did not form
      neurospheres in this culture condition. These NSCs differentiated into both
      neurons and glial cells in vivo after being transplanted intracranially into
      mouse striatum. NSCs could also be directly induced from adult human fibroblasts.
      The direct differentiation of partially reprogrammed cells may be useful for
      rapidly preparing NSCs with a strongly reduced propensity for tumorigenesis.

PMID- 22467475
TI  - Relationship between the hip joint capsule and piriformis tendon in a simulation
      of the modified Watson-Jones anterolateral approach in THA cadaver study.
AB  - Fifteen fresh frozen cadavers were used for a simulation of the modified Watson
      Jones anterolateral approach in an anatomical study. Several parameters were
      measured to evaluate the relation between the piriformis tendon insertion and hip
      joint capsule insertion. The anteroposterior diameter of the piriformis tendon
      was found to be greater than the medial-lateral diameter, and that the posterior
      part of the incised hip joint capsule is distant from the piriformis tendon as
      the piriformis is inserted into the extra-articular portion. We also found that
      it was important not to dissect the anteroproximal portion of the greater
      trochanter to prevent rupture of the piriformis tendon, whereas the posterior
      portion was relatively safe.

PMID- 22467476
TI  - Generation of a conditional allele for the mouse endothelial nitric oxide
      synthase gene.
AB  - Mice with endothelial nitric oxide synthase (eNOS) deletions have defined the
      crucial role of eNOS in vascular development, homeostasis, and pathology.
      However, cell specific eNOS function has not been determined, although an
      important role of eNOS has been suggested in multiple cell types. Here, we have
      generated a floxed eNOS allele in which exons 9-12, encoding the sites essential
      to eNOS activity, are flanked with loxP sites. Mice homozygous for the floxed
      allele showed normal eNOS protein levels and no overt phenotype. Conversely,
      homozygous mice with Cre-deleted alleles displayed truncated eNOS protein, lack
      of vascular NO production, and exhibited similar phenotype to eNOS knockout mice,
      including hypertension, low heart rate, and focal renal scarring. These findings
      demonstrate that the floxed allele is normal and it can be converted to a non
      functional eNOS allele through Cre recombination. This mouse will allow time- and
      cell-specific eNOS deletion.

PMID- 22467477
TI  - Chemical compositions of the marine algae Gracilaria salicornia (Rhodophyta) and
      Ulva lactuca (Chlorophyta) as a potential food source.
AB  - BACKGROUND: The nutritional compositions of two edible red (Gracilaria
      salicornia) and green (Ulva lactuca) seaweeds were determined to evaluate their
      possible uses as potential food ingredients. RESULTS: In general, these species
      contained limited amounts of lipids ranging between 0.99 and 2.00 g 100 g(-1) dry
      weight) and considerably high amount of minerals, especially in G. salicornia
      (38.91 g 100 g(-1) d.w.). The crude protein values varied between 9.58 and 10.69
      g 100 g(-1) d.w. Amounts for total amino acids were 889.78 +/- 22.64 mg g(-1)
      protein d.w. in G. salicornia and 543.3 +/- 15.14 mg g(-1) protein d.w. in U.
      lactuca. The most abundant fatty acids were C12:0, C16:0, C20:4 omega6 and C22:5
      omega3, in addition to C18:1 in G. salicornia. Both seaweed species were balanced
      sources of omega3 and omega6 fatty acids with a ratio of omega6/omega3 that
      varied between 1.2 and 1.17. Between the seaweeds investigated, high levels of K
      (2414.02-11 380.06 mg 100 g(-1) d.w.) were observed and the amounts of Ca, Na and
      Fe were higher than those reported for land plants. CONCLUSIONS: Thus, G.
      salicornia and U. lactuca may be utilised as value-added products for human
      nutrition purposes.

PMID- 22467478
TI  - The role of the inter-/supraspinous ligament complex in stand-alone interspinous
      process devices: a biomechanical and anatomic study.
AB  - BACKGROUND: Lumbar spinal stenosis (LSS) with neurogenic intermittent
      claudication is one of the most common degenerative spinal diseases in the
      elderly. For patients over 65 years with LSS, open decompression is the most
      frequent spinal surgery. One problem associated with decompression surgery is the
      emergence of instability, which is found in varying grades of severity. For some
      patients with LSS, interspinous process devices (IPD) may be a viable alternative
      to open decompression. The purpose of this study is to examine the destruction
      and changes to the interspinous and supraspinous ligament complex after
      percutanous IPD implantation. METHODS: Biomechanical and anatomic assessments
      were performed on the lumbar spine (L1-L4) of 11 fresh human cadavers. The
      biomechanical examination assayed the force necessary to disrupt the interspinous
      supraspinous ligament complex without and after implantation of an IPD. For the
      anatomic examination, one lumbar spine was plastinated. Serial 4-mm thick
      sections were cut in sagittal and horizontal planes. The macroanatomic
      positioning of the implants was then analysed. RESULTS: Biomechanics: The average
      age of the cadavers was 80.6+/-10.2 years. The minimum average disrupting forces
      measured 313.74+/-113.44 N without and 239.47+/-63.64 N after IPD implantation, a
      significant (p<0.018) decrease of an average 23.7%. Anatomy: After posterolateral
      percutaneous IPD implantation, the posterior third of the interspinous ligament,
      the supraspinous ligament, the thoracolumbar fascia and paraspinous muscles
      bordering the inter-/supraspinous ligament complex remained undamaged.
      CONCLUSION: The implantation of an interspinous "stand-alone" spacer
      significantly minimises the force necessary to disrupt the ISL/SSL complex. After
      posterolateral percutaneous IPD implantation, the thoracolumbar fascia and
      associated musculature, which act in synergy with the ISL/SSL complex to
      stabilise the vertebral column, remain intact.

PMID- 22467479
TI  - Did survival improve after the implementation of intraoperative neuronavigation
      and 3D ultrasound in glioblastoma surgery? A retrospective analysis of 192
      primary operations.
AB  - BACKGROUND: Numerous observational studies indicate that more aggressive
      resection may prolong survival in glioblastoma patients. In Trondheim, Norway,
      intraoperative 3D ultrasound has been in increasing use since November 1997. The
      aim of the present study was to examine if the introduction of 3D ultrasound and
      neuronavigation (i. e., the SonoWand(r) system) may have had an impact on overall
      survival. PATIENTS/MATERIAL AND METHODS: Patient data were obtained
      retrospectively for the 192 glio-blastoma patients who received surgery and
      postoperative radiotherapy between 1990 and 2005. Overall survival, before and
      after 1997, was compared using the log rank test. Possible confounders were
      adjusted for in a multivariate Cox regression analysis. RESULTS: We observed an
      increase in survival for patients in the last study period (9.6 vs. 11.9 months;
      HR = 0.7; p = 0.034). The significant improvement in the latest time period was
      sustained after adjusting for age, WHO performance status (>=2) and type of
      radiotherapy (normofractioned or hypofractioned), and chemotherapy (yes/no), p =
      0.034. 10 out of 14 patients who survived more than 3 years received treatment
      after the implementation of 3D ultrasound. CONCLUSION: Our study demonstrates
      that survival has improved within the same period that intraoperative ultrasound
      and neuronavigation was introduced and established in our department. The
      demonstrated association is a necessity for causation, but given the nature of
      this study, one must be cautious to claim causality. The improvement was,
      however, significant after adjustment for known major prognostic factors.

PMID- 22467480
TI  - Surgical strategies for supra- and infratentorially grown occipital meningeomas.
AB  - BACKGROUND: Extensive tentorial meningeomas which are growing supra- and
      infratentorially are a surgical challenge, and a distinct surgical strategy is
      required for good results. PATIENTS: 3 patients, 2 with asymptomatic tumor and 1
      with signs of increased intracranial pressure and visual disorder underwent
      microsurgery. RESULTS: In 2 patients, the semi-sitting position was taken. A
      lateralized occipital/suboccipital craniotomy with exposure of the confluens
      sinuum, transverse and superior sagittal sinus was performed. First, the dura was
      opened infratentorially allowing good cerebrospinal fluid (CSF) release. In a
      second step the dura was opened supratentorially sparing the sinus. The tumor was
      then removed completely without brain swelling or significant venous bleeding.
      One patient underwent surgery in prone position. A unilateral
      occipital/suboccipital craniotomy with exposure of the confluens sinuum and the
      ipsilateral transverse sinus was made. The dura was opened supratentorially. A
      resulting occipital lobe swelling made enlargement of the craniotomy and
      additional infratentorial dura opening necessary. All patients recovered well
      without postoperative morbidity. Complete tumor resection was confirmed by early
      postoperative MRI. CONCLUSION: The authors recommend a semi-sitting position
      (less venous bleeding, less brain swelling) and a lateralized occipital and
      suboccipital craniotomy for optimal control of the venous sinuses. Opening of the
      dura should start infratentorially to allow for CSF drainage and brain relaxation
      but should be combined with a sinus sparing supratentorial dura opening for
      adequate visualization and total meningioma removal.

PMID- 22467481
TI  - Intravascular infusion of lidocaine: a novel way to relieve sudden internal
      carotid artery occlusion in embolization of intracranial aneurysms.
AB  - BACKGROUND: Sudden internal carotid artery (ICA) occlusive vasospasm is a serious
      complication of intracranial aneurysm embolization. Conventional spasmolysis with
      papaverine yields a generally poor outcome. We believe that arterial infusion of
      lidocaine may offer a better outcome. MATERIALS AND METHODS: We retrospectively
      reviewed the outcome of patients treated with either papaverine or lidocaine
      infusion for vasospasm during embolization. RESULTS: 14 patients undergoing
      intracranial aneurysm embolization had a ICA occlusive vasospasm. Among the 8
      patients who received conventional treatment with papaverine the vasospasm
      improved partially in 5. In 3 cases, treatment was ineffective. 6 of the patients
      died within 3 days. 2 patients developed hemispheric infarction and underwent a
      decompressive craniectomy and subtotal resection of the infarct; 1 of these 2
      patients died after 4 months and the other was severely disabled. In the 6
      patients treated with lidocaine, spasmolysis and subsequent aneurysm treatment
      was successful in 5. In 1 patient who had preoperative stenosis of the carotid
      artery proximal to the aneurysm spasmolysis failed. CONCLUSIONS: ICA occlusive
      spasm is an extremely serious and often lethal complication in embolization of
      intracranial aneurysms. Conventional treatment with papaverine has a poor
      outcome, whereas arterial infusion of lidocaine may achieve better results.

PMID- 22467482
TI  - Fibrillary structure is key for hemostasis: a similar effect of collagen fleece
      and oxidized cellulose on experimental hemorrhagic brain injury.
AB  - BACKGROUND: The choice of the ideal hemostatic agent for intraoperative cerebral
      bleeding is under continuous debate. Our aim was to assess the influence of such
      materials on bleeding time in hemorrhagic cerebral contusions. We compared
      oxidized regenerated cellulose in fibrillar form (ORC) to microfibrillar collagen
      fleece (CF) in an experimental study. METHODS: N=50 Sprague Dawley rats underwent
      a bilateral craniectomy. 3 separate standardized superficial cortical impacts
      were inflicted using a high-speed drill. Immediately after lesion placement, each
      of the 3 lesions was covered with (a) nothing (control), (b) ORC, or (c) CF. We
      observed the 3 lesions with a surgical microscope. The bleeding times were
      recorded for each cerebral lesion and compared using ANOVA test. RESULTS: All
      traumatic lesions produced significant bleeding. The statistical analysis showed
      a clear reduction in bleeding time for groups treated with either ORC or CF
      compared to the control group. Lesions covered with ORC and CF showed no
      significant difference with regard to bleeding time. CONCLUSIONS: ORC and CF
      significantly reduce blood loss from hemorrhagic contusions. Our data suggest
      that they effectively reduce bleeding time. We advocate the use of hemostatic
      material for limiting bleeding from superficial cortical lesions.

PMID- 22467483
TI  - Evaluation of 2 hematology analyzers in body fluid mode versus flow cytometry
      immunophenotyping of mainly neurosurgical cerebrospinal fluid samples.
AB  - BACKGROUND: For CSF analysis, exact knowledge of the type and amount of cells is
      essential, especially for detection of infection or bleeding. The chamber count
      has been the current reference method to date, yet it is problematic due to its
      subjectivity depending on the examiner's skill and experience. Therefore, as a
      reference method, we used an impulse cytophotometric measurement with Epics XL
      owing to its improved objectify ability and compared this method to the
      measurement of CSF samples performed with the ADVIA 2120 and XE-5000. MATERIAL
      AND METHODS: 101 CSF samples were measured with the ADVIA 2120, XE-5000, and
      Epics XL. For impulse cytophotometric measurement, CD235a was used for
      identification of erythrocytes; CD45 for the entire leukocyte population; CD56,
      CD16 and CD14 for monocytes; CD3, CD4 and CD19 for lymphocytes;and CD13, CD15 and
      CD33 for neutrophile granulocytes. RESULTS: Regarding leukocyte measurements, a
      strong correlation was obtained between Epics XL and XE-5000 (r = 0.990), with
      the correlation between Epics XL and ADVIA 2120 not as strong (r = 0.538). This
      finding is due to the fact that with blood-stained CSF samples (erythrocytes
      >1,500/ul), no valid results were produced by the ADVIA 2120. In measurements of
      blood-free CSF samples, correlations between Epics XL, XE-5000, and ADVIA 2120
      were almost identical (r = 0.985 and r = 0.964). The same applies to the
      correlation between polymorphonuclear and mononuclear cells (range 0.920-0.972).
      In erythrocyte measurements, the correlation between XE-5000 and ADVIA 2120 was
      excellent (r = 0.945). Impulse cytophotometric measurement of erythrocytes with
      CD 238 antibodies did not appear to be functional. CONCLUSION: In the measurement
      of leukocytes in CSF with the ADVIA 2120, no valid results could be obtained in
      blood-stained CSF samples (erythrocytes >1,500/ul). In blood-free CSF samples
      (erythrocytes <1,500/ul), measurements of leukocytes, and polymorphonuclear and
      mononuclear cells performed with the ADVIA 2120 and XE-5000 produced almost
      identical good results. Determination of CSF cells with the XE-5000 is presently
      the best automated method for counting leukocytes of blood-stained CSF.

PMID- 22467484
TI  - Erdheim-Chester disease--a rare differential diagnosis of eosinophilic granuloma:
      a case report.

PMID- 22467485
TI  - Fluorescence-guided resection of spinal metastases of malignant glioma: report of
      2 cases.

PMID- 22467486
TI  - Partial corporectomy and open vertebroplasty via an anterolateral approach for
      metastatic destruction of the axis.

PMID- 22467487
TI  - Intradural perineural spread of mesothelioma causing myelopathy by tethering of
      the spinal cord.

PMID- 22467488
TI  - Herpes simplex encephalitis after neurosurgical operations: report of 2 cases and
      review of the literature.

PMID- 22467490
TI  - Day-case thyroid surgery.

PMID- 22467489
TI  - On the unyielding hydrophobic core of villin headpiece.
AB  - Villin headpiece (HP67) is a small, autonomously-folding domain that has become a
      model system for understanding the fundamental tenets governing protein folding.
      In this communication, we explore the role that Leu61 plays in the structure and
      stability of the construct. Deletion of Leu61 results in a completely unfolded
      protein that cannot be expressed in Escherichia coli. Omission of only the
      aliphatic leucine side chain (HP67 L61G) perturbed neither the backbone
      conformation nor the orientation of local hydrophobic side chains. As a result, a
      large, solvent-exposed hydrophobic pocket, a negative replica of the leucine side
      chain, was created on the surface. The loss of the hydrophobic interface between
      leucine 61 and the hydrophobic pocket destabilized the construct by ~3.3
      kcal/mol. Insertion of a single glycine residue immediately before Leu61 (HP67
      L61[GL]) was also highly destabilizing and had the effect of altering the
      backbone conformation (alpha-helix to pi-helix) in order to precisely preserve
      the wild-type position and conformation of all hydrophobic residues, including
      Leu61. In addition to demonstrating that the hydrophobic side-chain of Leu61 is
      critically important for the stability of villin headpiece, our results are
      consistent with the notion that the precise interactions present within the
      hydrophobic core, rather than the hydrogen bonds that define the secondary
      structure, specify a protein's fold.

PMID- 22467491
TI  - 2'-chloro-4'-aminoflavone derivatives selectively targeting hepatocarcinoma
      cells: convenient synthetic process, G(2)/M cell cycle arrest and apoptosis
      triggers.
AB  - A series of 2'-chloro-4'-nitroflavone and 2'-chloro-4'-aminoflavone derivatives
      were synthesized by a convenient synthetic process. The in vitro anti
      proliferation ability of these compounds was evaluated against hepatocarcinoma
      cells (HepG2), breast adenocarcinoma cells (MCF-7), and human chronic myelogenous
      leukemia cells (K562). Most of synthetic compounds possessed notable anti
      proliferation activity against HepG2 cells and little activity against MCF-7
      cells and K562 cells. In particular, compounds 4c and 4e exhibited high anti
      proliferation activity against HepG2 cells with IC(50) at about 2.0 uM. Further
      toxicity screening toward normal human hepatocytes indicated that some compounds
      had low toxicity against normal liver cells, among which 4e displayed very weak
      effects on QSG7701 and HL7702 cells, with IC(50) values >100 and 50 uM,
      respectively. Compound 4c, with the best anti-proliferation activity in amino
      substituted flavones (IC(50) = 2.0 uM), was selected for further evaluation of
      its effects on apoptosis and the cell cycle. HepG2 cells were exposed to this
      compound at 10 uM, which induced nuclear disassembly and DNA fragmentation. Flow
      cytometry analysis suggested that the population of apoptotic cells greatly
      increased in the 4c-treated HepG2 cells, and the cell cycle was arrested at the
      G(2)/M phase.

PMID- 22467492
TI  - Glucuronoxylomannan facilitates generation of chondrocytes from bone marrow
      derived mononuclear cells.
AB  - Chondrocyte generation is an important process in cartilage and bone repair.
      Factors facilitating the induction of chondrocyte need to be further
      investigated. The present study aims to investigate the role of
      glucuronoxylomannan (Gxm) in the generation of chondrocytes. Human bone marrow
      cells were prepared using to generate the chondrocytes in the presence of Gxm.
      The results showed that Gxm has the capacity to facilitate the generation of
      chondrocytes in which transforming growth factor (TGF)-beta played a critical
      role. The Bmmc-derived CD14+ cells were the major source of TGF-beta in the
      culture. The present study indicates that Gxm is a potential drug candidate to be
      used in the generation of chondrocyte.

PMID- 22467493
TI  - Experimental therapies for repair of the central nervous system: stem cells and
      tissue engineering.
AB  - Several stem cell-based therapeutic tools are currently being investigated for
      the regeneration of central nervous system (CNS) injuries. This review focuses on
      innovative approaches for CNS tissue repair via the use of implantable cellular
      devices. These devices are supported by biopharmaceuticals and conventional
      physiotherapy for the restoration of lost neuronal circuits and CNS function.
      This paper further reviews new and promising tools currently in pre-clinical and
      clinical tests for the treatment of CNS diseases where substantial loss of
      cellular and extracellular components of neural tissue has occurred such as
      stroke, encephalopathy and traumatic neural injuries. We also discuss selected 3D
      bioscaffolds co-cultured with clinically applicable human mesenchymal stem cells.
      Recent advances in neural tissue engineering and stem cell differentiation
      methods have shown promise for their clinical application in treating yet
      incurable CNS deficits.

PMID- 22467494
TI  - Establishment of a human nonluteinized granulosa cell line that transitions from
      the gonadotropin-independent to the gonadotropin-dependent status.
AB  - The ovary is a complex endocrine organ responsible for steroidogenesis and
      folliculogenesis. Follicles consist of oocytes and two primary steroidogenic cell
      types, the granulosa cells, and the theca cells. Immortalized human granulosa
      cells are essential for researching the mechanism of steroidogenesis and
      folliculogenesis. We obtained granulosa cells from a 35-yr-old female and
      immortalized them by lentivirus-mediated transfer of several genes so as to
      establish a human nonluteinized granulosa cell line (HGrC1). We subsequently
      characterized HGrC1 and investigated its steroidogenic performance. HGrC1
      expressed enzymes related to steroidogenesis, such as steroidogenic acute
      regulatory protein, CYP11A, aromatase, and gonadotropin receptors. Stimulation
      with FSH increased the mRNA levels of aromatase, which consequently induced the
      aromatization of androstenedione to estradiol. Activin A increased the mRNA
      levels of the FSH receptor, which were synergistically up-regulated with FSH
      stimulation. HGrC1 also expressed a series of ligands and receptors belonging to
      the TGF-beta superfamily. A Western blot analysis showed that bone morphogenetic
      protein (BMP)-4, BMP-6, and BMP-7 phosphorylated small mother against
      decapentaplegic (Smad)1/5/8, whereas growth differentiation factor-9
      phosphorylated Smad2/3. BMP-15 and anti-Mullerian hormone phosphorylated
      Smad1/5/8 while also weakly phosphorylating Smad2/3. These results indicate that
      HGrC1 may possess the characteristics of granulosa cells belonging to follicles
      in the early stage. HGrC1 might also be capable of displaying the growth
      transition from a gonadotropin-independent status to gonadotropin-dependent one.

PMID- 22467495
TI  - Minireview: The link between fat and bone: does mass beget mass?
AB  - Osteoporosis is less common in individuals with high fat mass. This putative
      osteoprotection is likely an adaptive mechanism that allows obese individuals to
      better carry their increased body mass. Recent studies have focused on hormones
      that link fat to bone. Adipokines, such as leptin, modulate bone cells through
      both direct and indirect actions, whereas molecules activating peroxisome
      proliferator-activated receptor gamma drive mesenchymal stem cell differentiation
      towards adipocytes away from the osteoblastic lineage. There is emerging evidence
      that bone-derived osteocalcin regulates insulin release and insulin sensitivity
      and, hence, might indirectly affect fat mass. Despite these molecular connections
      between fat and bone, animal and human studies call into question a primary role
      for body fat in determining bone mass. Mice devoid of fat do not have a skeletal
      phenotype, and in humans, the observed correlations between bone and body mass
      are not just due to adipose tissue. An improved understanding of the integrative
      physiology at the fat-bone interface should allow us develop therapies for both
      osteoporosis and obesity.

PMID- 22467496
TI  - Association study of neuregulin 1 gene polymorphisms with auditory P300 in
      schizophrenia.
AB  - Neuregulin 1 (NRG1), a gene involved with myelin production has been shown to
      have a positive correlation with schizophrenia. Event-related potentials (ERPs)
      studies provide the evidence of disturbed electrophysiologic marker in
      schizophrenia. The present study investigated the association of NRG1 genotypes
      with P300 in schizophrenia. Three polymorphisms in NRG1 gene were detected in 287
      Chinese Han schizophrenics and 120 healthy control subjects. Among the total
      sample, 140 patients and 96 controls underwent P300. There were no significant
      differences for genotype distributions and allele frequencies between
      schizophrenic group and the control. A significant difference was observed
      between the schizophrenic patients and controls in the AT haplotype, with Odds
      Ratio 0.304 (P = 0.000882, 95% CI = 0.145-0.636). P300 amplitude in the
      schizophrenic group was significantly lower than that of the controls at Fz, Cz,
      Pz. P300 latency in the schizophrenic group was also significantly longer than
      that of the controls at Cz, Pz, Fz. Significant differences of P300 latency
      between three genotypes of rs3924999 were found at Cz and Pz both in
      schizophrenic group and the controls. The G/G carriers of rs3924999 tended to
      perform worse in the P300 latency as compared to A/A or A/G carriers both in the
      schizophrenia and controls. There were no significant differences for P300
      latency and amplitude between schizophrenic group and controls for AT haplotype.
      NRG1 gene is a susceptible gene for Chinese Han schizophrenia and AT haplotype
      might have the protective role in the schizophrenia. Rs3924999 in NRG1 gene might
      functionally impact cognitive processing.

PMID- 22467497
TI  - Selected antimicrobial essential oils eradicate Pseudomonas spp. and
      Staphylococcus aureus biofilms.
AB  - Biofilms are difficult to eliminate with standard antimicrobial treatments due to
      their high antibiotic resistance relative to free-living cells. Here, we show
      that selected antimicrobial essential oils can eradicate bacteria within biofilms
      with higher efficiency than certain important antibiotics, making them
      interesting candidates for the treatment of biofilms.

PMID- 22467498
TI  - Transcriptional and enzymatic profiling of Pleurotus ostreatus laccase genes in
      submerged and solid-state fermentation cultures.
AB  - The genome of the white rot basidiomycete Pleurotus ostreatus includes 12 phenol
      oxidase (laccase) genes. In this study, we examined their expression profiles in
      different fungal strains under different culture conditions (submerged and solid
      cultures) and in the presence of a wheat straw extract, which was used as an
      inducer of the laccase gene family. We used a reverse transcription-quantitative
      PCR (RT-qPCR)-based approach and focused on determining the reaction parameters
      (in particular, the reference gene set for the normalization and reaction
      efficiency determinations) used to achieve an accurate estimation of the relative
      gene expression values. The results suggested that (i) laccase gene transcription
      is upregulated in the induced submerged fermentation (iSmF) cultures but
      downregulated in the solid fermentation (SSF) cultures, (ii) the Lacc2 and Lacc10
      genes are the main sources of laccase activity in the iSmF cultures upon
      induction with water-soluble wheat straw extracts, and (iii) an additional, as
      yet-uncharacterized activity (Unk1) is specifically induced in SSF cultures that
      complements the activity of Lacc2 and Lacc10. Moreover, both the enzymatic
      laccase activities and the Lacc gene family transcription profiles greatly differ
      between closely related strains. These differences can be targeted for
      biotechnological breeding programs for enzyme production in submerged
      fermentation reactors.

PMID- 22467500
TI  - Impacts of hematite nanoparticle exposure on biomechanical, adhesive, and surface
      electrical properties of Escherichia coli cells.
AB  - Despite a wealth of studies examining the toxicity of engineered nanomaterials,
      current knowledge on their cytotoxic mechanisms (particularly from a physical
      perspective) remains limited. In this work, we imaged and quantitatively
      characterized the biomechanical (hardness and elasticity), adhesive, and surface
      electrical properties of Escherichia coli cells with and without exposure to
      hematite nanoparticles (NPs) in an effort to advance our understanding of the
      cytotoxic impacts of nanomaterials. Both scanning electron microscopy (SEM) and
      atomic force microscopy (AFM) showed that E. coli cells had noticeable
      deformation with hematite treatment for 45 min with a statistical significance.
      The hematite-treated cells became significantly harder or stiffer than untreated
      ones, as evidenced by indentation and spring constant measurements. The average
      indentation of the hematite-treated E. coli cells was 120 nm, which is
      significantly lower (P < 0.01) than that of the untreated cells (approximately
      400 nm). The spring constant of hematite-treated E. coli cells (0.28 +/- 0.11
      nN/nm) was about 20 times higher than that of untreated ones (0.01 +/- 0.01
      nN/nm). The zeta potential of E. coli cells, measured by dynamic light scattering
      (DLS), was shown to shift from -4 +/- 2 mV to -27 +/- 8 mV with progressive
      surface adsorption of hematite NPs, a finding which is consistent with the local
      surface potential measured by Kelvin probe force microscopy (KPFM). Overall, the
      reported findings quantitatively revealed the adverse impacts of nanomaterial
      exposure on physical properties of bacterial cells and should provide insight
      into the toxicity mechanisms of nanomaterials.

PMID- 22467499
TI  - Role of Aspergillus niger acrA in arsenic resistance and its use as the basis for
      an arsenic biosensor.
AB  - Arsenic contamination of groundwater sources is a major issue worldwide, since
      exposure to high levels of arsenic has been linked to a variety of health
      problems. Effective methods of detection are thus greatly needed as preventive
      measures. In an effort to develop a fungal biosensor for arsenic, we first
      identified seven putative arsenic metabolism and transport genes in Aspergillus
      niger, a widely used industrial organism that is generally regarded as safe
      (GRAS). Among the genes tested for RNA expression in response to arsenate, acrA,
      encoding a putative plasma membrane arsenite efflux pump, displayed an over 200
      fold increase in gene expression in response to arsenate. We characterized the
      function of this A. niger protein in arsenic efflux by gene knockout and
      confirmed that AcrA was located at the cell membrane using an enhanced green
      fluorescent protein (eGFP) fusion construct. Based on our observations, we
      developed a putative biosensor strain containing a construct of the native
      promoter of acrA fused with egfp. We analyzed the fluorescence of this biosensor
      strain in the presence of arsenic using confocal microscopy and
      spectrofluorimetry. The biosensor strain reliably detected both arsenite and
      arsenate in the range of 1.8 to 180 MUg/liter, which encompasses the threshold
      concentrations for drinking water set by the World Health Organization (10 and 50
      MUg/liter).

PMID- 22467501
TI  - Biofilm growth and near-infrared radiation-driven photosynthesis of the
      chlorophyll d-containing cyanobacterium Acaryochloris marina.
AB  - The cyanobacterium Acaryochloris marina is the only known phototroph harboring
      chlorophyll (Chl) d. It is easy to cultivate it in a planktonic growth mode, and
      A. marina cultures have been subject to detailed biochemical and biophysical
      characterization. In natural situations, A. marina is mainly found associated
      with surfaces, but this growth mode has not been studied yet. Here, we show that
      the A. marina type strain MBIC11017 inoculated into alginate beads forms dense
      biofilm-like cell clusters, as in natural A. marina biofilms, characterized by
      strong O(2) concentration gradients that change with irradiance. Biofilm growth
      under both visible radiation (VIS, 400 to 700 nm) and near-infrared radiation
      (NIR, ~700 to 730 nm) yielded maximal cell-specific growth rates of 0.38 per day
      and 0.64 per day, respectively. The population doubling times were 1.09 and 1.82
      days for NIR and visible light, respectively. The photosynthesis versus
      irradiance curves showed saturation at a photon irradiance of E(k) (saturating
      irradiance) >250 MUmol photons m(-2) s(-1) for blue light but no clear saturation
      at 365 MUmol photons m(-2) s(-1) for NIR. The maximal gross photosynthesis rates
      in the aggregates were ~1,272 MUmol O(2) mg Chl d(-1) h(-1) (NIR) and ~1,128
      MUmol O(2) mg Chl d(-1) h(-1) (VIS). The photosynthetic efficiency (alpha) values
      were higher in NIR-irradiated cells [(268 +/- 0.29) * 10(-6) m(2) mg Chl d(-1)
      (mean +/- standard deviation)] than under blue light [(231 +/- 0.22) * 10(-6)
      m(2) mg Chl d(-1)]. A. marina is well adapted to a biofilm growth mode under both
      visible and NIR irradiance and under O(2) conditions ranging from anoxia to
      hyperoxia, explaining its presence in natural niches with similar environmental
      conditions.

PMID- 22467502
TI  - Diversity of integron- and culture-associated antibiotic resistance genes in
      freshwater floc.
AB  - Clinically important antibiotic resistance genes were detected in culturable
      bacteria and class 1 integron gene cassettes recovered from suspended floc, a
      significant aquatic repository for microorganisms and trace elements, across
      freshwater systems variably impacted by anthropogenic activities. Antibiotic
      resistance gene cassettes in floc total community DNA differed appreciably in
      number and type from genes detected in bacteria cultured from floc. The number of
      floc antibiotic resistance gene cassette types detected across sites was
      positively correlated with total (the sum of Ag, As, Cu, and Pb) trace element
      concentrations in aqueous solution and in a component of floc readily accessible
      to bacteria. In particular, concentrations of Cu and Pb in the floc component
      were positively correlated with floc resistance gene cassette diversity.
      Collectively, these results identify suspended floc as an important reservoir,
      distinct from bulk water and bed sediment, for antibiotic resistance in aquatic
      environments ranging from heavily impacted urban sites to remote areas of nature
      reserves and indicate that trace elements, particularly Cu and Pb, are
      geochemical markers of resistance diversity in this environmental reservoir. The
      increase in contamination of global water supplies suggests that aquatic
      environments will become an even more important reservoir of clinically important
      antibiotic resistance in the future.

PMID- 22467503
TI  - Soil fungal cellobiohydrolase I gene (cbhI) composition and expression in a
      loblolly pine plantation under conditions of elevated atmospheric CO2 and
      nitrogen fertilization.
AB  - The simultaneous increase of atmospheric CO(2) and nitrogen (N) deposition to
      terrestrial ecosystems is predicted to alter plant productivity and,
      consequently, to change the amount and quality of above- and belowground carbon
      entering forest soils. It is not known how such changes will impact the
      composition and function of soil fungal communities that play a key role in
      degrading complex carbon. We sequenced the fungal cellobiohydrolase I gene (cbhI)
      from soil DNA and cDNA to compare the richness and composition of resident and
      expressed cbhI genes at a U.S. Department of Energy free air-carbon dioxide
      enrichment (FACE) site (NC), which had been exposed to elevated atmospheric CO(2)
      and/or N fertilization treatment for several years. Our results provide evidence
      that the richness and composition of the cellulolytic fungi surveyed in this
      study were distinct in the DNA- and cDNA-based gene surveys and were dominated by
      Basidiomycota that have low or no representation in public databases. The surveys
      did not detect differences in richness or phylum-level composition of cbhI
      containing, cellulolytic fungi that correlated with elevated CO(2) or N
      fertilization at the time of sampling.

PMID- 22467504
TI  - Isolation of Legionella pneumophila from pluvial floods by amoebal coculture.
AB  - Viable Legionella pneumophila bacteria were isolated by amoebal coculture from
      pluvial floods after intense rainfall and from water collected at sewage
      treatment plants. Several isolated L. pneumophila strains belonged to sequence
      types that have been previously identified in patients.

PMID- 22467505
TI  - Contact-free inactivation of Candida albicans biofilms by cold atmospheric air
      plasma.
AB  - Candida albicans is one of the main species able to form a biofilm on almost any
      surface, causing both skin and superficial mucosal infections. The worldwide
      increase in antifungal resistance has led to a decrease in the efficacy of
      standard therapies, prolonging treatment time and increasing health care costs.
      Therefore, the aim of this work was to demonstrate the applicability of
      atmospheric plasma at room temperature for inactivating C. albicans growing in
      biofilms without thermally damaging heat-sensitive materials. This so-called cold
      atmospheric plasma is produced by applying high voltage to accelerate electrons,
      which ionize the surrounding air, leading to the production of charged particles,
      reactive species, and photons. A newly developed plasma device was used, which
      exhibits a large plasma-generating surface area of 9 by 13 cm (117 cm(2)).
      Different time points were selected to achieve an optimum inactivation efficacy
      range of >=3 log(10) to 5 log(10) reduction in CFU per milliliter, and the
      results were compared with those of 70% ethanol. The results obtained show that
      contact-free antifungal inactivation of Candida biofilms by cold atmospheric
      plasma is a promising tool for disinfection of surfaces (and items) in both
      health care settings and the food industry, where ethanol disinfection should be
      avoided.

PMID- 22467506
TI  - Efficacy of octenidine hydrochloride for reducing Escherichia coli O157:H7,
      Salmonella spp., and Listeria monocytogenes on cattle hides.
AB  - The efficacy of octenidine hydrochloride (OH; 0.025, 0.15, and 0.25%) for
      inactivating Escherichia coli O157:H7, Salmonella spp., and Listeria
      monocytogenes on cattle hides was investigated at 23 degrees C in the presence
      and absence of bovine feces. All tested concentrations of OH were effective in
      decreasing more than 5.0 log CFU of bacteria/cm(2) in 5 min (P < 0.01). The
      results suggest that OH could be used to decontaminate cattle hides; however,
      further studies under commercial settings are necessary to validate these
      results.

PMID- 22467507
TI  - Composition and seasonal variation of Rhipicephalus turanicus and Rhipicephalus
      sanguineus bacterial communities.
AB  - A 16S rRNA gene approach, including 454 pyrosequencing and quantitative PCR
      (qPCR), was used to describe the bacterial community in Rhipicephalus turanicus
      and to evaluate the dynamics of key bacterial tenants of adult ticks during the
      active questing season. The bacterial community structure of Rh. turanicus was
      characterized by high dominance of Coxiella and Rickettsia and extremely low
      taxonomic diversity. Parallel diagnostic PCR further revealed a novel Coxiella
      species which was present and numerically dominant in all individual ticks tested
      (n = 187). Coxiella sp. densities were significantly higher in female versus male
      ticks and were overall stable throughout the questing season. In addition, we
      revealed the presence of the novel Coxiella sp. in Rh. sanguineus adult ticks,
      eggs, and hatched larvae, indicating its vertical transmission. The presence of
      both spotted fever group Rickettsia spp. (SFGR) and non-SFGR was verified in the
      various individual ticks. The prevalence and density of Rickettsia spp. were very
      low compared to those of Coxiella sp. Furthermore, Rickettsia sp. densities were
      similar in males and females and significantly declined toward the end of the
      questing season. No correlation was found between Coxiella sp. and Rickettsia sp.
      densities. These results suggest different control mechanisms in the tick over
      its different bacterial populations and point to an obligatory and facultative
      association between the two tick species and Coxiella sp. and Rickettsia spp.,
      respectively.

PMID- 22467508
TI  - Biofilms reduce solar disinfection of Cryptosporidium parvum oocysts.
AB  - Solar radiation reduces Cryptosporidium infectivity. Biofilms grown from stream
      microbial assemblages inoculated with oocysts were exposed to solar radiation.
      The infectivity of oocysts attached at the biofilm surface and oocysts suspended
      in water was about half that of oocysts attached at the base of a 32-MUm biofilm.

PMID- 22467509
TI  - High-throughput sequence-based analysis of the intestinal microbiota of weanling
      pigs fed genetically modified MON810 maize expressing Bacillus thuringiensis
      Cry1Ab (Bt maize) for 31 days.
AB  - The objective of this study was to investigate if feeding genetically modified
      (GM) MON810 maize expressing the Bacillus thuringiensis insecticidal protein (Bt
      maize) had any effects on the porcine intestinal microbiota. Eighteen pigs were
      weaned at ~28 days and, following a 6-day acclimatization period, were assigned
      to diets containing either GM (Bt MON810) maize or non-GM isogenic parent line
      maize for 31 days (n = 9/treatment). Effects on the porcine intestinal microbiota
      were assessed through culture-dependent and -independent approaches. Fecal,
      cecal, and ileal counts of total anaerobes, Enterobacteriaceae, and Lactobacillus
      were not significantly different between pigs fed the isogenic or Bt maize-based
      diets. Furthermore, high-throughput 16S rRNA gene sequencing revealed few
      differences in the compositions of the cecal microbiotas. The only differences
      were that pigs fed the Bt maize diet had higher cecal abundance of
      Enterococcaceae (0.06 versus 0%; P < 0.05), Erysipelotrichaceae (1.28 versus
      1.17%; P < 0.05), and Bifidobacterium (0.04 versus 0%; P < 0.05) and lower
      abundance of Blautia (0.23 versus 0.40%; P < 0.05) than pigs fed the isogenic
      maize diet. A lower enzyme-resistant starch content in the Bt maize, which is
      most likely a result of normal variation and not due to the genetic modification,
      may account for some of the differences observed within the cecal microbiotas.
      These results indicate that Bt maize is well tolerated by the porcine intestinal
      microbiota and provide additional data for safety assessment of Bt maize.
      Furthermore, these data can potentially be extrapolated to humans, considering
      the suitability of pigs as a human model.

PMID- 22467510
TI  - Efficient production of polymyxin in the surrogate host Bacillus subtilis by
      introducing a foreign ectB gene and disrupting the abrB gene.
AB  - In our previous study, Bacillus subtilis strain BSK3S, containing a polymyxin
      biosynthetic gene cluster from Paenibacillus polymyxa, could produce polymyxin
      only in the presence of exogenously added L-2,4-diaminobutyric acid (Dab). The
      dependence of polymyxin production on exogenous Dab was removed by introducing an
      ectB gene encoding the diaminobutyrate synthase of P. polymyxa into BSK3S
      (resulting in strain BSK4). We found, by observing the complete inhibition of
      polymyxin synthesis when the spo0A gene was knocked out (strain BSK4-0A), that
      Spo0A is indispensable for the production of polymyxin. Interestingly, the abrB
      spo0A double-knockout mutant, BSK4-0A-rB, and the single abrB mutant, BSK4-rB,
      showed 1.7- and 2.3-fold increases, respectively, in polymyxin production over
      that of BSK4. These results coincided with the transcription levels of pmxA in
      the strains observed by quantitative real-time PCR (qRT-PCR). The AbrB protein
      was shown to bind directly to the upstream region of pmxA, indicating that AbrB
      directly inhibits the transcription of polymyxin biosynthetic genes. The BSK4-rB
      strain, producing high levels of polymyxin, will be useful for the development
      and production of novel polymyxin derivatives.

PMID- 22467512
TI  - Unusual formation of the median nerve associated with the third head of biceps
      brachii.

PMID- 22467511
TI  - Colorectal cancer in inflammatory bowel diseases: a population-based study (1976
      2008).
AB  - BACKGROUND: Few data are available on the incidence, characteristics, treatment,
      and prognosis of inflammatory bowel disease (IBD)-associated colorectal cancer
      (CRC) in population-based cohorts. METHODS: Among the 19,451 new cases of CRC
      recorded in the Burgundy digestive cancer registry between 1976 and 2008, all
      cases of IBD-associated CRC were identified. Incidence rates were age
      standardized according to the world standard population. Prognosis was determined
      using univariate and multivariate relative survival. RESULTS: Thirty-eight IBD
      associated CRC were identified (ulcerative colitis, n = 29; Crohn's disease, n =
      9). The mean age at CRC diagnosis was greater for patients without IBD than those
      with IBD (70.9 vs. 56.9 years, respectively; P < 0.001). Distributions of gender,
      stage at presentation, location, and histological type of CRC did not differ from
      those of sporadic cases. The overall world age-standardized incidence of IBD
      associated CRC per 100,000 was 0.11 (standard deviation [SD]: 0.03) for men and
      0.06 (SD: 0.02) for women. Only age was independently associated with IBD
      associated CRC (odds ratio [OR]: 0.22; 95% confidence interval [CI]: 0.12-0.43; P
      < 0.001). Treatment modalities did not differ between IBD and non-IBD patients.
      Five-year relative survival was 51.9% (95% CI: 51.1-52.8%) in non-IBD patients
      and 41.3% (95% CI: 24.6-57.2%) in IBD patients (P = 0.201). After adjustment for
      age, gender, and stage at diagnosis, the excess hazard of death was 1.46 times
      higher in IBD than in non-IBD patients (95% CI: 0.94-2.27; P = 0.070).
      CONCLUSIONS: Apart from age, the characteristics of IBD-associated CRC were
      similar to those of non-IBD CRC. The prognosis of CRC may be poorer in patients
      with IBD than in those without IBD.

PMID- 22467513
TI  - Conditional expression of Lodavin, an avidin-tagged LDL receptor, for biotin
      mediated applications in vivo.
AB  - Lodavin represents an engineered fusion protein that consists of a cytoplasmic
      and a transmembrane domain of the human low-density lipoprotein receptor coupled
      to an extracellular avidin monomer. Biotinylated compounds have been successfully
      targeted to Lodavin-expressing cells that have been transduced by a Lodavin
      containing virus, and the targeting is based on the high affinity between biotin
      and avidin. We engineered a Rosa26 (R26R) knock-in Lodavin mouse to develop
      biotin-based applications such as targeted drug delivery, cell purification, and
      tissue imaging in vivo. A cDNA encoding Lodavin was inserted downstream of a
      floxed betageo resistance gene in the R26R locus in embryonic stem cells, and a
      germ line-derived R26RLodavin mouse line was generated. Efficient removal of the
      floxed betageo cassette and conditional activation of Lodavin expression was
      achieved as a result of crossing the R26RLodavin mice with HoxB7-Cre, Wnt4-Cre,
      or Tie1-Cre mice. In summary, the R26RLodavin mouse line may provide a useful
      tool for testing and developing applications with the aid of avidin and biotin
      interaction.

PMID- 22467514
TI  - Effects of oxygen and antioxidants on the lipid oxidation and yellow
      discolouration of film from red tilapia mince.
AB  - BACKGROUND: Generally, biodegradable films from fish muscle protein become yellow
      after preparation. This discolouration is more likely associated with lipid
      oxidation and can be prevented by minimising the oxidation in the films. Thus,
      the effects of oxygen and antioxidants on lipid oxidation and yellow
      discolouration of film from red tilapia mince during storage were investigated.
      RESULTS: Both films prepared at pH 3 and 11, and kept under atmosphere containing
      100% N(2) had the lowest TBARS value with the concomitant lowest b* and DeltaE*
      values during storage (P < 0.05), when compared with other films kept in air and
      a 100% O(2) atmosphere. Films prepared at pH 3 and incorporated with antioxidants
      (Trolox and catechin) at all levels (100, 200 and 400 mg L(-1) film-forming
      solution) had the lowest TBARS value, b* and DeltaE* values during storage,
      indicating the retardation of lipid oxidation and yellow discolouration in films.
      Nevertheless, films prepared at pH 11 had no difference in TBARS values, in
      comparison with control film, regardless of antioxidant incorporation.
      Coincidentally, increases in b* and DeltaE* values were observed in those films.
      CONCLUSIONS: Lipid oxidation was the main factor inducing yellow discolouration
      of film exposed to oxygen and the incorporation of antioxidants in film prepared
      at acidic pH was able to prevent yellow discolouration of resulting film.

PMID- 22467515
TI  - Severe Mycoplasma pneumoniae infection requiring extracorporeal membrane
      oxygenation with concomitant ischemic stroke in a child.
AB  - Mycoplasma pneumoniae is one of the most common agents causing respiratory
      disease in children. The most common extra-pulmonary manifestations of M.
      pneumoniae include central nervous system involvement, with stroke being an
      uncommon but devastating consequence. We present a 13-year-old girl with severe
      respiratory disease requiring extracorporeal membrane oxygenation, who developed
      ischemic stroke associated with clinical and serologic evidence of M. pneumoniae.
      A case of M. pneumoniae causing this degree of respiratory failure associated
      with stroke has not been previously reported. Prompt recognition of severe
      mycoplasmal infection may allow for earlier treatment and concomitant evaluation
      of neurologic injury.

PMID- 22467516
TI  - Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione
      derivatives as dual-binding site acetylcholinesterase inhibitors.
AB  - A new series of 2-(diethylaminoalkyl)-isoindoline-1,3-dione derivatives intended
      as dual binding site cholinesterase inhibitors were designed using molecular
      modeling and evaluated as inhibitors of acetylcholinesterase (AChE),
      butyrylcholinesterase (BuChE), and the formation of the beta-amyloid (Abeta)
      plaques. For AChE inhibitory activity, the spectrophotometric method of Ellman
      and the electrophoretically mediated microanalysis assay were used, giving good
      results. Most of the synthesized compounds had AChE inhibitory activity with
      IC(50) values ranging from IC(50) = 0.9 to 19.5 uM and weak Abeta anti
      aggregation inhibitory activity. These results support the outcome of docking
      studies which tested compounds targeting both the catalytic active site (CAS) and
      the peripheral anionic site (PAS) of AChE. The most promising selective AChE
      inhibitors are compounds 10 (IC(50) = 1.2 uM) and 11 (IC(50) = 1.1 uM), with 6-7
      methylene chains, which also inhibit Abeta fibril formation.

PMID- 22467517
TI  - [Mental health and work].

PMID- 22467518
TI  - [Outpatient sociotherapy according to german code of social law v failed].

PMID- 22467519
TI  - The Ly6 neurotoxin-like molecule target of wit regulates spontaneous
      neurotransmitter release at the developing neuromuscular junction in Drosophila.
AB  - Refinement of neural circuits during development requires formation and
      elimination of synaptic connections, a process governed by activity-dependent
      mechanisms and developmental genetic programs. Bone Morphogenetic Protein (BMP)
      retrograde signaling through the type II receptor Wishful thinking (Wit) is
      essential for synaptic growth and functional development of the Drosophila larval
      neuromuscular junction. However, little is known about the genes that are
      regulated by the pathway to effect synaptic growth and proper synaptic
      transmission. We have identified a transcriptional target of wit (twit), whose
      expression in motoneurons depends on Wit activity. Null twit mutants are viable
      and fertile, but recapitulate some of the electrophysiological phenotypes of wit
      mutants, such as decreased frequency and amplitude of miniature excitatory
      junction potentials. Other wit phenotypes, such as decreased synaptic terminal
      size and evoked excitatory junction potentials, are not found in twit mutants,
      suggesting that homeostatic compensation of presynaptic release is intact in twit
      mutants and that Wit regulates additional genes to accomplish proper synaptic
      maturation. Twit is a glycosylphosphatidylinositol-anchored protein of the
      Lymphocyte antigen 6 family (Ly-6), and neuronal expression of a twit transgene
      rescues twit's mutant phenotypes. Importantly, twit expression partially rescues
      diminished frequency of miniature excitatory synaptic potentials in wit mutants.
      This further supports the conclusions that Twit is signaling in larval
      motoneurons and an essential effector of the retrograde BMP signal. Taken
      together, our results suggest that retrograde BMP signaling regulates spontaneous
      neurotransmitter release by activating the transcription of the Ly-6 gene twit.

PMID- 22467520
TI  - Induction of angiogenesis and osteogenesis in surgically revascularized frozen
      bone allografts by sustained delivery of FGF-2 and VEGF.
AB  - Large conventional bone allografts are susceptible to fracture and nonunion due
      to incomplete revascularization and insufficient bone remodeling. We aim to
      improve bone blood flow and bone remodeling using surgical angiogenesis combined
      with delivery of fibroblast growth factor (FGF-2) and vascular endothelial growth
      factor (VEGF). Frozen femoral allografts were heterotopically transplanted in a
      rat model. The saphenous arteriovenous bundle was implanted within the graft
      medullary canal. Simultaneously, biodegradable microspheres containing phosphate
      buffered saline (control), FGF-2, VEGF, or FGF-2 + VEGF were placed within the
      graft. Rats were sacrificed at 4 and 18 weeks. Angiogenesis was determined by
      quantifying bone capillary density and measuring cortical bone blood flow. Bone
      remodeling was assessed by histology, histomorphometry, and alkaline phosphatase
      activity. VEGF significantly increased angiogenesis and bone remodeling at 4 and
      18 weeks. FGF-2 did not elicit a strong angiogenic or osteogenic response. No
      synergistic effect of FGF-2 + VEGF was observed. VEGF delivered in microspheres
      had superior long-term effect on angiogenesis and osteogenesis in surgically
      revascularized frozen bone structural allografts as compared to FGF-2 or FGF-2 +
      VEGF. Continuous and localized delivery of VEGF by microencapsulation has
      promising clinical potential by inducing a durable angiogenic and osteogenic
      response in frozen allografts.

PMID- 22467521
TI  - JCV+ Patients with Inflammatory bowel disease show elevated plasma levels of MIG
      and SCF.

PMID- 22467522
TI  - Association of CRHR1 and CRHR2 with major depressive disorder and panic disorder
      in a Japanese population.
AB  - Major depressive disorder (MDD) and panic disorder (PD) are common and disabling
      medical disorders with stress and genetic components. Dysregulation of the stress
      response of the hypothalamic-pituitary-adrenal axis, including the corticotrophin
      releasing hormone (CRH) signaling via primary receptors (CRHR1 and CRHR2), is
      considered to play a major role for onset and recurrence in MDD and PD. To
      confirm the association of CRHR1 and CRHR2 with MDD and PD, we investigated 12
      single nucleotide polymorphisms (SNPs) (rs4076452, rs7209436, rs110402, rs242924,
      rs242940, and rs173365 for CRHR1 and rs4722999, rs3779250, rs2267710, rs1076292,
      rs2284217, and rs226771 for CRHR2) in MDD patients (n = 173), PD patients (n =
      180), and healthy controls (n = 285). The SNP rs110402 and rs242924 in the CRHR1
      gene and the rs3779250 in the CRHR2 gene were associated with MDD. The SNP
      rs242924 in the CRHR1 gene was also associated with PD. The T-A-T-G-G haplotype
      consisting of rs7209436 and rs173365 in CRHR1 was positively associated with MDD.
      The T-A haplotype consisting of rs7209436 and rs110402 in CRHR1 was positively
      associated with MDD. The C-C haplotype consisting of rs4722999 and rs37790 in
      CRHR1 was associated with PD. These results provide support for an association of
      CRHR1 and CRHR2 with MDD and PD.

PMID- 22467523
TI  - Can trauma cause tibial intraneural ganglion cysts at the superior tibiofibular
      joint?

PMID- 22467524
TI  - Design and one-pot and microwave-assisted synthesis of 2-amino/5-aryl-1,3,4
      oxadiazoles bearing a benzimidazole moiety as antioxidants.
AB  - In this study, two new series of 2-amino-1,3,4-oxadiazoles and 5-aryl-1,3,4
      oxadiazoles carrying a benzimidazole moiety were synthesized. The antioxidant
      properties of these compounds were investigated in vitro by the determination of
      the microsomal NADPH-dependent inhibition of lipid peroxidation levels (LP), the
      microsomal ethoxyresorufin O-deethylase activity (EROD), and DPPH radical
      scavenger effects. Among the tested compounds, 2-[(2-(4-chlorophenyl)-1H
      benzo[d]imidazole-1-yl)methyl]-5-(4-fluorophenyl)-1,3,4-oxadiazole (9) was found
      to be the most active compound in all three in vitro systems.

PMID- 22467525
TI  - Developmental and genetic aspects of congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a frequent occurring cause of neonatal
      respiratory distress and occurs 1 in every 3,000 liveborns. Ventilatory support
      and pharmaceutical treatment of the co-occurring lung hypoplasia and pulmonary
      hypertension are insufficient in, respectively, 20% of isolated cases and 60% of
      complex ones leading to early perinatal death. The exact cause of CDH remains to
      be identified in the majority of human CDH patients and prognostic factors
      predicting treatment refraction are largely unknown. Their identification is
      hampered by the multifactorial and heterogenic nature of this congenital anomaly.
      However, application of high-resolution molecular cytogenetic techniques to
      patients' DNA now enables detection of chromosomal aberrations in 30% of the
      patients. Furthermore, recent insights in rodent embryogenesis pointed to a
      specific disruption of the early mesenchymal structures in the primordial
      diaphragm of CDH-induced offspring. Together, these data allowed for the
      introduction of new hypotheses on CDH pathogenesis, although many issues remain
      to be resolved. In this review, we have combined these new insights and remaining
      questions on diaphragm pathogenesis with a concise overview of the clinical,
      embryological, and genetic data available.

PMID- 22467526
TI  - Bacterial adherence to separated modular components in joint prosthesis: a
      clinical study.
AB  - Bacterial adherence on total joint replacement implants may lead to biofilm
      formation and implant-related osteoarticular infection. It is unclear if
      different biomaterials in the prosthetic components are more prone to facilitate
      this bacterial adherence, although ultrahigh molecular weight polyethylene
      (UHMWPE) component exchange in modular systems has been clinically utilized in
      the early management of these infections. To clarify if the amount of clinically
      adhered microorganisms was related to the material or the component, we
      investigated retrieved implants from infected joint replacements. Thirty-two
      patients were revised after confirmed implant-related infection through positive
      cultures. Eighty-seven total joint components (hip and knee) were obtained and
      separately sonicated following a previously published protocol. Cultures were
      quantified, and detected colony forming units (CFU) were adjusted according to
      the component surface and compared based on the component material and location.
      Variable adherence of bacteria to chrome cobalt alloys, UHMWPE, hydroxyapatite
      coated components, and titanium alloys. The commonest isolated organisms were
      Staphylococcus epidermidis (23 of 87 components) and Staphylococcus aureus (10 of
      87). Twelve components did not show any microorganism adhered despite location in
      an infected joint, with positive cultures in other components. A mixed linear
      model adjusted for random effects (the random effect being the infected patient)
      obtained convergence for the CFU/mm(2) variable, but could not confirm a
      significantly higher adherence to a particular component or to a particular
      biomaterial. Therefore, the bacterial adherence primarily depends on the
      infective microorganism and the response of each individual patient, rather than
      materials or components.

PMID- 22467527
TI  - Prohemostatic interventions in trauma: resuscitation-associated coagulopathy,
      acute traumatic coagulopathy, hemostatic resuscitation, and other hemostatic
      interventions.
AB  - Trauma is the most common cause of death in the young and hemorrhage is the most
      important cause of death in patients with trauma. Recently redefined pathways of
      inflammation and coagulation, together with hypothermia and acidosis contribute
      to trauma-associated coagulopathy and aggravation of bleeding. Pharmacological
      prohemostatic agents may be useful to (partly) correct the coagulopathy in trauma
      patients and may serve as useful adjunctive treatment options in patients with
      severe blood loss after trauma. Recombinant factor VIIa, fibrinogen and
      prothrombin complex concentrates, and antifibrinolytic agents have been evaluated
      in clinical trials. These interventions show promising effects but their efficacy
      in reducing clinically important outcome parameters need to be confirmed in
      clinical studies.

PMID- 22467528
TI  - Intensity and duration of anticoagulation therapy in antiphospholipid syndrome.
AB  - Antithrombotic drugs are the therapeutic cornerstone for patients with
      antiphospholipid syndrome (APS) and thrombosis. Choosing the specific agent
      (vitamin K antagonists or antiplatelet drugs), the intensity of anticoagulation
      (e.g., international normalized ratio [INR] range 2.0 to 3.0 or 3.0 to 4.0), and
      the duration of treatment has been a recurrent matter of debate. A recent
      consensus document recommends warfarin to an INR range of 2.0 to 3.0 for patients
      with a first venous thromboembolic event. Higher anticoagulation intensity is
      recommended for patients presenting with arterial events. Combined therapy with
      warfarin and aspirin is another possibility, but some authors recommend standard
      intensity warfarin or aspirin, either as monotherapy. In general, a more intense
      regimen is warranted for high-risk patients. On the basis of an increased risk of
      recurrence during the first 6 months following warfarin withdrawal, long-term
      anticoagulation is considered the standard treatment. Nevertheless,
      anticoagulation regimes of shorter duration could be given in selected patients
      with venous thromboembolism who have transient risk factors and a low-risk
      profile.

PMID- 22467529
TI  - Vestigial tooth anatomy and tusk nomenclature for monodon monoceros.
AB  - Narwhal tusks, although well described and characterized within publications, are
      clouded by contradictory references, which refer to them as both incisors and
      canines. Vestigial teeth are briefly mentioned in the scientific literature with
      limited descriptions and no image renderings. This study first examines narwhal
      maxillary osteoanatomy to determine whether the erupted tusks are best described
      as incisiform or caniniform teeth. The study also offers evidence to support the
      evolutionary obsolescence of the vestigial teeth through anatomic, morphologic,
      and histologic descriptions. Examination of 131 skull samples, including 110
      museum skull specimens and 21 harvested skulls, revealed the erupted tusks
      surrounded by maxillary bone over the entire length of their bone socket
      insertion, and are thus more accurately termed caniniform or canine teeth. The
      anatomy, morphology, and development of vestigial teeth in five skull samples are
      more fully described and documented. Vestigial tooth samples included 14 embedded
      pairs or individual teeth that were partially exposed or removed from the
      maxillary bone. Their location was posterior, ventral, and lateral to the tusks,
      although male vestigial teeth often exfoliate in the mouth lodging between the
      palatal tissue and underlying maxillary bone. Their myriad morphologies, sizes,
      and eruption patterns suggest that these teeth are no longer guided by function
      but rather by random germ cell differentiation and may eventually cease
      expression entirely. The conclusions reached are that the narwhal tusks are the
      expression of canine teeth and that vestigial teeth have no apparent functional
      characteristics and are following a pattern consistent with evolutionary
      obsolescence.

PMID- 22467530
TI  - The relationship between depressive symptoms, quality of life, and swallowing
      function in head and neck cancer patients 1 year after definitive therapy.
AB  - OBJECTIVES/HYPOTHESIS: To determine the incidence of depression in head and neck
      cancer (HNCA) patients following definitive treatment and the relationship
      between depression and head and neck-specific measures of quality of life and
      function. STUDY DESIGN: Prospective cohort analysis. METHODS: Two hundred forty
      six patients were evaluated with the Beck Depression Inventory Fast-Screen (BDI
      FS), University of Washington Quality of Life (UW QOL), Voice Handicap Index
      (VHI), and MD Anderson Dysphagia Inventory (MDADI) questionnaires. Patients with
      a preexisting diagnosis of depression were excluded. RESULTS: Complete 1-year
      post-treatment data were available for 46 HNCA patients, with depression
      identified in nine patients (20%). On multivariate analysis, depression was
      significantly associated with poorer global UW QOL (beta = -40.3, P < .001) and
      overall MDADI scores (beta = -21.8, P = .038), but not with VHI scores, after
      controlling for other clinical variables including initial treatment modality.
      BDI-FS scores were significantly correlated with global UW QOL (r = -0.7, P <
      .001) and overall MDADI scores (r = -0.5, P = .0045), and global UW QOL
      correlated significantly with overall MDADI scores (r = 0.4, P = .0166). After
      controlling for clinical variables, MDADI, and VHI scores, only depression was
      associated with global UW QOL score (beta = -30.5, P = .019). CONCLUSIONS: There
      is a high incidence of depressive symptoms in HNCA patients at 1 year following
      definitive therapy, which is independent of primary treatment modality and is
      associated with poorer global QOL and MDADI scores. Although depression and
      swallowing function are highly correlated, depression has a greater effect on QOL
      than swallowing scores, suggesting that early identification and aggressive
      treatment of patients with depressive symptoms is warranted to maximize post
      treatment QOL.

PMID- 22467531
TI  - Automatic detection of melanoma progression by histological analysis of secondary
      sites.
AB  - We present results from machine classification of melanoma biopsies sectioned and
      stained with hematoxylin/eosin (H&E) on tissue microarrays (TMA). The four stages
      of melanoma progression were represented by seven tissue types, including benign
      nevus, primary tumors with radial and vertical growth patterns (stage I) and four
      secondary metastatic tumors: subcutaneous (stage II), lymph node (stage III),
      gastrointestinal and soft tissue (stage IV). Our experiment setup comprised
      14,208 image samples based on 164 TMA cores. In our experiments, we constructed
      an HE color space by digitally deconvolving the RGB images into separate H
      (hematoxylin) and E (eosin) channels. We also compared three different
      classifiers: Weighted Neighbor Distance (WND), Radial Basis Functions (RBF), and
      k-Nearest Neighbors (kNN). We found that the HE color space consistently
      outperformed other color spaces with all three classifiers, while the different
      classifiers did not have as large of an effect on accuracy. This showed that a
      more physiologically relevant representation of color can have a larger effect on
      correct image interpretation than downstream processing steps. We were able to
      correctly classify individual fields of view with an average of 96% accuracy when
      randomly splitting the dataset into training and test fields. We also obtained a
      classification accuracy of 100% when testing entire cores that were not
      previously used in training (four random trials with one test core for each of 7
      classes, 28 tests total). Because each core corresponded to a different patient,
      this test more closely mimics a clinically relevant setting where new patients
      are evaluated based on training with previous cases. The analysis method used in
      this study contains no parameters or adjustments that are specific to melanoma
      morphology, suggesting it can be used for analyzing other tissues and phenotypes,
      as well as potentially different image modalities and contrast techniques.

PMID- 22467532
TI  - Genetic mouse models for skin research: strategies and resources.
AB  - A number of features contributed to establishing the mouse as the favorite model
      organism for skin research: the genetic and pathophysiological similarities to
      humans, the small size and relatively short reproductive period, meaning low
      maintenance costs, and the availability of sophisticated tools for manipulating
      the genome, gametes, and embryos. While initial studies depended on strains
      displaying skin abnormalities due to spontaneous genetic mutations, the
      availability of the transgenic and knockout technologies and their astonishing
      perfection during the last decades allowed the development of mouse lines
      permitting any imaginable genetic modification including gene inactivation,
      substitution, modification, or overexpression. While these technologies have
      already contributed to the functional analysis of several genes and processes
      related to skin research, continued progress requires understanding, awareness,
      and access to these mouse resources. This review will identify the strategies
      currently employed for the genetic manipulation of mice in skin research, and
      outline current resources and their limitations.

PMID- 22467533
TI  - Anti-tumor necrosis factor and postoperative complications in Crohn's disease:
      systematic review and meta-analysis.
AB  - BACKGROUND: Anti-tumor necrosis factor (TNF) antibodies are efficacious in
      patients with Crohn's disease (CD) but the influence of these medications on
      surgical outcomes in CD patients has been frequently debated. The aim was to
      evaluate the impact of preoperative treatment with anti-TNF antibodies on
      postoperative complications in CD patients undergoing abdominal surgery. METHODS:
      A systematic review and meta-analysis of comparative cohort studies was performed
      assessing postoperative complication rates in CD patients who were treated with
      anti-TNF antibodies within 3 months before surgery versus patients who were not.
      The primary outcome was overall complication rate within 1 month of surgery.
      Secondary outcomes included the rate of infectious and noninfectious
      complications. The quality of studies was assessed based on selection of patients
      and controls, comparability of the study groups, and assessment of outcomes. Odds
      ratios (OR) with 95% confidence intervals (CIs) were computed. RESULTS: A total
      of eight studies including 1641 patients were included in our meta-analysis.
      Preoperative infliximab therapy in CD patients undergoing abdominal surgery was
      associated with a trend toward an increased rate of total complications (OR 1.72,
      95% CI, 0.93-3.19). Anti-TNF treatments were associated with a modestly increased
      risk of infectious complications (OR 1.50, 95% CI 1.08-2.08), mostly remote from
      the surgical site (OR 2.07 95% CI 1.30-3.30) and with a trend toward a higher
      rate of noninfectious complications (OR 2.00, 95% CI 0.89-4.46). CONCLUSION:
      Preoperative infliximab treatment is associated with an increased risk of
      postoperative infectious complications, mostly nonlocal. A trend toward an
      increased risk of noninfectious and overall complications was also observed.

PMID- 22467534
TI  - Molecular characterization of a cancer-related single nucleotide polymorphism in
      the pro-inflammatory interleukin-1B gene.
AB  - Interleukin-1beta is a key pro-inflammatory cytokine that has been associated
      with chronic inflammation and inflammation-related cancer initiation and
      progression. There are inter-individual differences in IL1B expression which may
      be due to single nucleotide polymorphisms (SNPs) in the regulatory regions of the
      gene. We have previously shown that a SNP located in the promoter of the IL1B
      gene (the IL1B T-31C SNP) was associated with lung cancer risk. Interestingly,
      the presence of the C allele was also associated with reduced IL1B expression in
      normal lung tissue of lung cancer patients. In the present study, we found that
      differential binding patterns of nuclear proteins to oligonucleotide probes
      containing the IL1B -31C allele compared to those with the T allele were due to
      specific binding of the transcription factor Yin Yang 1 (YY1). We further found
      evidence that specific recruitment of YY1 to the -31C region of the IL1B promoter
      regulated IL1B gene expression using siRNA directed towards YY1. The results
      indicate that the presence of a C allele at the -31 position may lead to
      decreased expression of the IL1B gene due to a specific binding of YY1 in lung
      epithelial cells. Our study provides functional significance of allelic variation
      at a single locus in the IL1B promoter and contributes to understanding the
      regulation of IL1B in inflammation-related carcinogenesis.

PMID- 22467535
TI  - Synthesis, antitumor, and antibacterial activity of bis[4,5-diarylimidazol-2
      ylidene]methane derivatives.
AB  - Cationic [bis(1,3-diethyl-4,5-diarylimidazol-2-ylidene)]Au(I) bromide complexes
      have demonstrated considerable potential as new antitumor agents. In order to
      investigate whether the gold is crucial for the antitumor activity, the imidazole
      ligands were connected by a methylene bridge. Biological evaluation revealed that
      bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]methane compounds exhibited growth
      inhibition effects against mammary (MCF-7 and MDA-MB 231) and colon (HT-29)
      carcinoma cell lines. In comparison with gold complexes, the methylene
      derivatives showed drastically reduced cell growth inhibitory properties.
      However, the growth of bacteria was significantly inhibited by bis[1,3-diethyl
      4,5-bis(4-methoxyphenyl)imidazol-2-ylidene]methane dibromide (4) and opens a new
      application of this compound type.

PMID- 22467536
TI  - The fraction of NO in exhaled air and estimates of alveolar NO in adolescents
      with asthma: methodological aspects.
AB  - RATIONALE: This study investigated the oral contribution to exhaled NO in young
      people with asthma and its potential effects on estimated alveolar NO (Calv(NO)
      ), a proposed marker of inflammation in peripheral airways. Secondary aims were
      to investigate the effects of various exhalation flow-rates and the feasibility
      of different proposed adjustments of (Calv(NO) ) for trumpet model and axial
      diffusion (TMAD). METHODS: Exhaled NO at flow rates of 50-300 ml/sec, and
      salivary nitrite was measured before and after antibacterial mouthwash in 29
      healthy young people (10-20 years) and 29 with asthma (10-19 years). Calv(NO) was
      calculated using the slope-intercept model with and without TMAD adjustment.
      RESULTS: Exhaled NO at 50 ml/sec decreased significantly after mouthwash, to a
      similar degree in asthmatic and healthy subjects (8.8% vs. 9.8%, P = 0.49). The
      two groups had similar salivary nitrite levels (56.4 vs. 78.4 uM, P = 0.25).
      Calv(NO) was not significantly decreased by mouthwash. Calv(NO) levels were
      similar when flow-rates between 50-200 or 100-300 ml/sec were used (P = 0.34 in
      asthmatics and P = 0.90 in healthy subjects). A positive association was found
      between bronchial and alveolar NO in asthmatic subjects and this disappeared
      after the TMAD-adjustment. Negative TMAD-adjusted Calv(NO) values were found in a
      minority of the subjects. CONCLUSIONS: Young people with and without asthma have
      similar salivary nitrite levels and oral contributions to exhaled NO and
      therefore no antibacterial mouthwash is necessary in routine use. TMAD
      corrections of alveolar NO could be successfully applied in young people with
      asthma and yielded negative results only in a minority of subjects.

PMID- 22467537
TI  - Interfacial shear strength of bioactive-coated carbon fiber reinforced
      polyetheretherketone after in vivo implantation.
AB  - Despite the excellent osseointegration of carbon-fiber-reinforced
      polyetheretherketone (CFR/PEEK) with a surface hydroxyapatite (HA) coating, the
      bone-implant interfacial shear strength of HA-coated CFR/PEEK after
      osseointegration is unclear. We examined the interfacial shear strength of HA
      coated CFR/PEEK implants after in vivo implantation in a rabbit femur-implant
      pull-out test model. HA coating was performed by a newly developed method.
      Uncoated CFR/PEEK, HA-coated blasted titanium alloy, and uncoated blasted
      titanium alloy were used as control implants. The implants were inserted into
      drilled femoral cortex, and pull-out tests were conducted after 6 and 12 weeks of
      implantation to determine maximum interfacial shear strength. The HA-coated
      CFR/PEEK (15.7  +/- 4.5 MPa) and HA-coated titanium alloy (14.1  +/-  6.0 MPa)
      exhibited significantly larger interfacial shear strengths than the uncoated
      CFR/PEEK (7.7 +/- 1.8 MPa) and the uncoated titanium alloy (7.8  +/-  2.1 MPa) at
      6 weeks. At 12 weeks, only the uncoated CFR/PEEK (8.3  +/-  3.0 MPa) exhibited a
      significantly smaller interfacial shear strength, as compared to the HA-coated
      CFR/PEEK (17.4  +/-  3.6 MPa), HA-coated titanium alloy (14.2  +/-  4.8 MPa), and
      uncoated titanium alloy (15.0  +/-  2.6 MPa). Surface analysis of the removed
      implants revealed detachment of the HA layer in both the HA-coated CFR/PEEK and
      titanium alloy implants. The proposed novel HA coating method of CFR/PEEK
      significantly increased interfacial shear strength between bone and CFR/PEEK. The
      achieved interfacial shear strength of the HA-coated CFR/PEEK implant is of the
      same level as that of grit-blasted titanium alloy with HA.

PMID- 22467538
TI  - [Research in inflammatory bowel disease - an obsolescent model or new
      perspectives?].

PMID- 22467539
TI  - [Preference of patients with inflammatory bowel disease regarding information and
      shared decision-making: results from a cross-sectional survey in Germany].
AB  - BACKGROUND: Evidence-based and consented pathways for patients with inflammatory
      bowel diseases (IBD, Crohn's disease, ulcerative colitis) call for tailored
      education programmes to foster shared decision-making and patient self
      management. Their preferences should be taken into account. METHODS: In 2005 a
      cross-sectional postal questionnaire survey was conducted in different regions of
      Germany. Adult patients with ulcerative colitis (UC) or Crohn's disease (CD) were
      recruited from specialised gastroenterological practices, university outpatient
      clinics and the member registry of the relevant patient organisation DCCV. They
      returned a questionnaire including (inter)nationally established scales (e. g.,
      HADS) as well as questions on their information needs, preferred information
      sources and their role in decision-making. RESULTS: Data of 1056 responders could
      be analysed (65 % female; CD: 58 %; DCCV member: 71 %). The mean age of the
      patients was 42 (SD 12,8) years. Almost all patients wanted more information on
      "treatment alternatives" (83 %), "causes of disease" (80 %) and "what can I
      (still) do by myself" (79 %). 27 % of the patients asked for more information on
      15 or more of overall 19 topics. The high information need was significantly
      associated with HADS potential depressive disorder (score > 8) and HADS probable
      anxiety disorder (score > 10). Most IBD patients (70 %) obviously regard their
      physicians as the most desirable source of information, 67 % prefer an active
      involvement in clinical decision-making. CONCLUSIONS: The data demonstrate high
      information needs of IBD patients and may serve in the planning of future
      educational programmes.

PMID- 22467540
TI  - [With the scalpel against the immune system: HIV infection complicated by an
      unclear colitis].
AB  - A 35-year-old Kenian lady with advanced immunodeficiency due to HIV infection
      started on an antiretroviral therapy. Five months later, a severe colitis was
      diagnosed, however, no causal pathogen could be found. In order to avoid imminent
      perforation, a hemicolectomy became necessary, and immediately the symptoms and
      inflammation markers normalized rapidly. M. tuberculosis could be proven in
      culture in a draining abdominal lymph node. We assume that the severe
      inflammation was caused by an immune restoration inflammatory syndrome (IRIS).
      Essentials in diagnosis, pathogenesis and therapy of IRIS are discussed.

PMID- 22467541
TI  - A new type of rendezvous: introduction of laparo-endoscopy in selected patients.
AB  - OBJECTIVE: The aim of this work is to demonstrate the introduction of laparo
      endoscopy and to investigate the year-long experience with its use. PATIENTS AND
      METHODS: In a subgroup of patients with cholecystolithiasis, concomitant
      lithiasis of the common bile duct may also be present. When the preoperative
      endoscopic cholangiopancreatography, performed as a result of a suspected
      choledocholithiasis, was unsuccessful, a "rendezvous" ERCP, laparo-endoscopy, is
      performed. After a survey of the international literature on the method, and a
      description of its technique, the authors give a review of the cases of their own
      10 patients, which were all successful. RESULTS: These findings emphasise the
      advantages of the new method in a certain subgroup of patients over the
      conventional, sequential approach (preoperative ERCP followed by laparoscopic
      cholecystectomy), and also give technical hints obtained during their performance
      of the operations up to now. CONCLUSIONS: These results underline the importance
      of team work that involves the cooperation of a gastroenterologist, a surgeon and
      an anaesthesiologist in the indication, organisation and implementation of the
      intervention.

PMID- 22467542
TI  - [Endoscopic resection of a rare gastric adenoma (pyloric gland adenoma) with
      transition into a well-differentiated adenocarcinoma].
AB  - We present the case of a 76-year-old lady in whom the work-up for iron-deficiency
      anaemia resulted in the finding of a giant gastric polyp. The polyp could be
      completely removed endoscopically. The final histology showed the rare entity of
      a pyloric gland adenoma with focal transition into a well-differentiated
      adenocarcinoma. The patient is well after a follow-up of 12 months. Pyloric gland
      adenoma was first described in 1990. In spite of its benign histological
      appearance, a transition into adenocarcinoma has been reported in up to 30 % of
      the cases. Thus, although relatively rare, the gastroenterologist/endoscopist, as
      well as the pathologist should be aware of the entity of pyloric gland adenoma.

PMID- 22467543
TI  - Calcineurin inhibitors or anti-TNF-alpha agents in severe ulcerative colitis:
      available options and limitations.
AB  - A majority of patients with ulcerative colitis (UC) respond to medical therapy
      and remain in remission. However, approximately 20 % of UC patients experience
      severe relapses that require hospitalization. For these cases, intravenous
      corticosteroids are the established first-line treatment and 70 % of patients
      respond. Patients who do not respond to corticosteroids within 48 to 72 hours
      should receive calcineurin inhibitors, anti-TNF-alpha therapy or total
      proctocolectomy, which must be selected based on clinical, endoscopic and
      laboratory parameters and patient preference. The selection of second-line
      medical therapy after steroid failure, surgery and the benefits of medical
      salvage therapy following second-line therapy failure represent current
      challenges in the treatment of acute steroid-refractory colitis. Patients and
      physicians must realize that immunosuppressive therapies, especially in
      combination, bear the risk of serious and fatal infections. Therefore, decisions
      regarding short- and long-term treatment strategies must consider the efficacy
      and potential toxicity of pharmacological interventions and the quality of life
      after restorative proctocolectomy with ileal pouch-anal anastomosis.

PMID- 22467545
TI  - [Alcohol consumption and gastric cancer risk: which role does beer play?].

PMID- 22467544
TI  - [Short version S3 guideline sedation for gastrointestinal endoscopy und
      medicolegal implications].
AB  - With the publication of the first German S3 guideline on sedation for
      gastrointestinal endoscopy, the topic sedation has recently attracted the
      interest not only of physicians and medical assistants but also of the general
      public. It remains the topic of many, often controversial, discussions. This
      discussion arises mainly because of the fact that with the guideline - although
      giving a structured survey of the already existing requirements on structural as
      well as personnel qualifications - more emphasis is placed on the necessary
      personnel resources, standards for adequate patient information on the sedation,
      and risk stratification for the patient with the publication of the guideline.

PMID- 22467546
TI  - Biometry and statistical analysis of the styloid process.
AB  - The hyoid apparatus is made up of three osteocartilaginous elements that go from
      the base of the cranium to the hyoid bone; the portions, cranially to caudally,
      are as follow: stylohyal, ceratohyal, and apohyal. Fusion and ossification of
      these three components will bring about somewhat long stylohyoid processes,
      whereas the stylohyal portion is the one that gives rise to the authentic
      stylohyoid process. The variability of the hyoid apparatus may imply associated
      compressive pathologies, for which an etiological diagnosis is important. A study
      was undertaken of 835 craniums of a homogeneous male and female adult population,
      involving a morphometric analysis of the styloid processes in which
      quantification was made of the following continual descriptive measurements:
      thickness, length, sagittal angle, transversal angle, and the distance between
      vertices. Multivariate data analysis techniques were applied to the data set to
      describe the relationships between these measurements. The main conclusion from
      the analysis is the existence of two different groups of styloid processes and
      the derivation of a prediction score.

PMID- 22467547
TI  - Effects of ethnicity and socioeconomic status on survival and severity of
      fibrosis in liver transplant recipients with hepatitis C virus.
AB  - The ethnicity and socioeconomic status of the host may affect the progression of
      hepatitis C virus (HCV). We aimed to compare survival and fibrosis progression in
      Hispanic white (HW) and non-Hispanic white (NHW) recipients of liver
      transplantation (LT) with HCV. All HW and NHW patients with HCV who underwent
      transplantation between January 2000 and December 2007 at 2 centers were
      retrospectively assessed. The primary outcomes were the time to death, death or
      graft loss due to HCV, and significant fibrosis [at least stage 2 of 4]. Five
      hundred eleven patients were studied (159 HW patients and 352 NHW patients), and
      the baseline demographics were similar for the 2 groups. NHW patients were more
      likely to be male, to have attended college, and to have private insurance, and
      they had a higher median household income (MHI). The unadjusted rates of survival
      (log-rank P = 0.93), death or graft loss due to HCV (P = 0.89), and significant
      fibrosis (P = 0.95) were similar between groups. In a multivariate analysis
      controlling for center, age [hazard ratio (HR) per 10 years = 1.43, P = 0.01],
      donor age (HR per 10 years = 1.25, P < 0.001), and rejection (HR = 1.47, P =
      0.048) predicted death, whereas HW ethnicity (HR = 1.06, P = 0.77) was not
      significant. Independent predictors of significant fibrosis were HW ethnicity (HR
      = 2.42, P = 0.046), MHI (HR per $10,000 = 1.11, P = 0.01), donor age (HR per 10
      years = 1.13, P = 0.02), cold ischemia time (HR = 1.06, P = 0.03), and the
      interaction between ethnicity and MHI (HR = 0.82, P = 0.03). In conclusion, there
      is no difference in post-LT survival or graft loss due to HCV between HW patients
      and NHW patients. Socioeconomic factors may influence disease severity; this is
      suggested by our findings of more significant fibrosis in HW patients with a low
      MHI.

PMID- 22467548
TI  - Mortality associated with carbapenem-resistant Klebsiella pneumoniae infections
      in liver transplant recipients.
AB  - Resistant bacterial infections are important causes of morbidity and mortality
      after liver transplantation (LT). This was a retrospective cohort study
      evaluating the outcomes associated with carbapenem-resistant Klebsiella
      pneumoniae (CRKP) infections after LT. In a 2005-2006 cohort of 175 consecutive
      LT recipients, 91 infection episodes were observed in 61 patients (35%). The
      mortality rate 1 year after LT was 18% (32/175). Enterococcus (43%) and
      Klebsiella species (37%) were the most frequently isolated bacteria. CRKP
      infections occurred in 14 patients, and 10 of these patients (71%) died. Seven of
      these deaths occurred within 30 days of the CRKP infection. The median time to
      the onset of CRKP infections was 12 days (range = 1-126 days) after LT. The
      survival rate was significantly lower for patients with a CRKP infection versus
      patients without a CRKP infection (29% versus 86%, log-rank P < 0.001). In a
      multivariate analysis, the only pre-LT and post-LT clinical variables
      significantly associated with death were a Model for End-Stage Liver Disease
      score >= 30 (hazard ratio = 3.4, P = 0.04) and a post-LT CRKP infection (hazard
      ratio = 4.9, P = 0.007). In conclusion, the outcomes associated with CRKP
      infections in LT recipients are poor. Because the optimal treatment strategies
      for CRKP infections remain undefined, improved preventive strategies are needed
      to curtail the devastating impact of CRKP in LT recipients.

PMID- 22467549
TI  - Risk factors and outcomes of failed endoscopic retrograde
      cholangiopancreatography in liver transplant recipients with anastomotic biliary
      strictures: a case-control study.
AB  - Anastomotic strictures (ASs) of the biliary duct after liver transplantation (LT)
      are primarily managed with endoscopic retrograde cholangiopancreatography (ERCP),
      but in some cases, this fails because of difficulties in passing the strictures.
      The aim of this case-control study was to examine specific risk factors for
      initial ERCP failure and the outcomes of percutaneous transhepatic
      cholangiography (PTC) as a second-line approach in LT recipients with ASs.
      Between January 2002 and December 2010, we identified LT recipients with ASs who
      experienced initial ERCP failure (which was defined as the inability to traverse
      the AS with guidewires in 2 or more consecutive procedures). A period-matched
      control group (ratio = 1:2) with ASs and initial ERCP success was analyzed.
      Preoperative, intraoperative, postoperative, and endoscopic variables were
      evaluated as risk factors. The outcomes of PTC and the need for
      hepaticojejunostomy (HJ) or retransplantation were evaluated. Seventeen cases who
      experienced initial ERCP failure were compared with 34 controls. The median times
      from LT to ERCP were similar (8.7 months for cases and 8.6 months for controls, P
      = not significant). A multivariate analysis revealed that previous bile leaks
      [odds ratio (OR) = 6.07, 95% confidence interval (CI) = 1.0-36.5] and more than 4
      U of intraoperatively transfused red blood cells (OR = 11.51, 95% CI = 1.9-71.2)
      were independent risk factors for failure. PTC was an effective second-line
      treatment in only 3 of 12 cases (25%). The need for HJ was more frequent for the
      cases (13/17 or 76.5%) versus the controls (7/34 or 20.6%, P < 0.001). One
      patient in each group underwent retransplantation (P = not significant). In
      conclusion, previous bile leaks and high packed red blood cell transfusion
      requirements during surgery are risk factors for initial ERCP failure in LT
      recipients with ASs. A high proportion of these patients will need surgery as
      their final therapy.

PMID- 22467550
TI  - There is plenty for everyone: transection of the infracardiac inferior vena cava
      during organ recovery.

PMID- 22467551
TI  - Fluoroquinolones are not a blanket cover for gram-negative bacilli.

PMID- 22467552
TI  - Extended survival of SH-SY5Y cells following overexpression of Lys67Glu
      neuroglobin is associated with stabilization of DeltapsiM.
AB  - Overwhelming evidence indicates that a high level of expression of the protein
      neuroglobin protects neurons in vitro, in animal models, and in humans, against
      cell death associated with hypoxic and amyloid insult. We have previously showed
      that neuroglobin protects neuronal cells from the mitochondrial pathway of
      apoptosis induced by the BH3 mimetic, by preventing cytochrome c-triggered
      activation of caspase 9. Here, using cell and molecular biology approaches, we
      generated a particular neuroglobin mutant, Lys67Glu, overexpression of which
      confers a significant protection from the BH3 mimetic (TW-37)-induced apoptosis
      in human neuroblastoma SH-SY5Y cells. The cumulative inhibition of caspase 9
      activation is significantly enhanced in Lys67Glu neuroglobin-expressing cells, as
      compared to wild-type neuroglobin expressing cells. A multiparameter flow
      cytometry analysis of TW-37-treated cells revealed that inhibition of caspase 9
      activity by Lys67Glu neuroglobin is associated with the preservation of the
      mitochondrial transmembrane potential (Deltapsi(M) ), as well as a decreased rate
      of cytochrome crelease from the mitochondria.

PMID- 22467553
TI  - Ambipolar charge transport in "traditional" organic hole transport layers.
AB  - Organic semiconductors are often labeled as electron or hole transport materials
      due to the primary role they perform in devices. However, despite these labels we
      have shown using time-of-flight that two of the traditional "hole transport
      materials" TPD and NPB are actually excellent electron transporters the electron
      transport properties of which are comparable to those for holes.

PMID- 22467554
TI  - What's new in veins?
AB  - Reflux cannot be interpreted without knowledge of the function of the calf muscle
      pump. The presence or absence of reflux alone has an insufficient predictive
      value for excellent functional treatment results. Valves are not simple moving
      slips but have an autonomous 4-step cycle movement that helps the calf muscle
      pump to be very effective. New calculations of the Starling equilibrium have
      shown that capillary filtration fraction returns mainly by the lymphatics. All
      these new findings help the phlebologist design a more precise and thus better
      treatment plan in phlebology practice.

PMID- 22467555
TI  - Commentary on "Late gastrointestinal complications of inferior vena cava filter
      placement: case report and literature review".

PMID- 22467556
TI  - A prominent Eustachian valve dividing the right atrium imaged by three
      dimensional transesophageal echocardiography.
AB  - A 63-year-old man underwent transesophageal echocardiography (TEE) to rule out
      left atrial thrombi prior to cardioversion. Initial two-dimensional TEE with
      color flow Doppler imaging was suggestive of an atrial septal defect. However,
      three-dimensional TEE imaging revealed that the unusually large elongated
      Eustachian valve extended toward the superior vena cava and mimicked the
      interatrial septum, while the true septum was located more posteriorly than the
      Eustachian valve. Three-dimensional TEE imaging was crucial to understanding the
      anatomical relationship between the Eustachian valve and the interatrial septum
      and hence proved helpful in characterizing this unusual anatomical variant.

PMID- 22467557
TI  - Applying Motivational Interviewing to the initiation of long-acting injectable
      atypical antipsychotics.
AB  - OBJECTIVE: Non-concordance with pharmacotherapy is common in psychiatric
      patients. Long-acting injectable atypical antipsychotic (LAI AA) medication may
      improve adherence but patients and clinicians may be reluctant to consider this
      alternative. This paper describes the application of Motivational Interviewing
      (MI) to the commencement of LAI AA. METHOD: We developed a workshop applying the
      principles of MI to address medication adherence through the use of LAIs. This
      includes a training video to illustrate the following motivational techniques, as
      summarised by the acronym OARS: (a) Open questions; (b) Affirmation of patients'
      self-efficacy and support; (c) Reflections of patients' thoughts, desires,
      abilities, reasons, needs, and commitments; (d) Summaries of the patient's
      history to promote consideration of change. RESULTS: We delivered four workshops
      across Canada. Results of feedback (n=25) were encouraging. CONCLUSIONS:
      Motivational Interviewing has many applications in psychiatric care for
      engagement in treatment, reduction in alcohol or substance misuse, and improving
      medication acceptance and adherence. Further research is required to assess
      whether changes in physicians' views are reflected in improved adherence.

PMID- 22467558
TI  - It's raining mental health commissions: prospects and pitfalls in driving mental
      health reform.
AB  - OBJECTIVE: Partly in response to ongoing concerns about the state of mental
      health care, several jurisdictions across Australia, including the federal
      government, are hoping to drive change via the establishment of a mental health
      commission. This is the first of two articles in a series which aims to describe
      the background to this new trend. The commissions are being established with
      different powers and structures. This variety is explored and considered against
      a typology of commissions. Some consistent themes and goals emerge. The paper
      then provides a contemporary assessment of the 'state of play' of the nascent
      commissions and describes important emerging issues and differences between the
      models. CONCLUSION: There are significant differences not only in the construct
      of the respective commissions but also in the political circumstances in which
      each must work. At the same time, the problems facing mental health in Australia
      are ubiquitous and profound. For commissions to be successful they will require
      not only astute leadership but also durable, bipartisan political support and an
      enduring capacity to generate new resources for the mental health sector.

PMID- 22467559
TI  - Walking on thin ice: the use of triple antidepressant combinations in refractory
      melancholic depression.
AB  - OBJECTIVE: To report on the outcome of cases of refractory depression treated
      with a combination of three antidepressant agents. METHOD: Retrospective case
      series. RESULTS: Three of the four patients made a good recovery. One patient
      developed transient increased agitation and exacerbation of pre-existing
      confusion. CONCLUSION: The use of a triple antidepressant combination may be a
      treatment option, albeit unorthodox and inelegant, in very specific circumstances
      such as for patients with refractory melancholic depression who have only
      partially responded to vigorous pharmacological treatment with combined
      antidepressants and are unwilling to use, or are unsuitable for, established
      treatments, such as lithium augmentation or electro-convulsive therapy (ECT).

PMID- 22467560
TI  - A framework for exploring the potential of routine outcome measurement to improve
      mental health care.
AB  - OBJECTIVE: To present a framework for exploring the potential applications of
      routine outcome measurement (ROM) to improve clinical practice. CONCLUSIONS: ROM
      is now commonplace in Australian mental health services, but it is fair to say
      that it has not yet achieved its potential in guiding service quality
      improvements. The framework described in this paper articulates the key
      components of ROM, noting that data from standardized outcome measures must be
      augmented by contextual information from other datasets. It considers the key
      users of ROM, and suggests the kind of questions that ROM might answer for each
      user group. It presents the use of ROM as a cycle of understanding the context,
      prioritization, brainstorming and planning, action and review. It is hoped that
      this framework might help to maximize the clinical utility of ROM at a number of
      levels.

PMID- 22467561
TI  - Mental health planning for children and youth: is it developmentally appropriate?
AB  - OBJECTIVES: We aim to provide an overview of current issues facing child and
      adolescent mental health services and the provision of developmentally informed
      and appropriate care. METHOD: We review developmental models of mental disorder
      and the impact on service design. RESULTS: Developmental issues can shape service
      design. CONCLUSIONS: Mental health services need to be informed and responsive to
      changing developmental needs and of the context of child development in terms of
      family and attachment relationships. Children and adolescents have specific needs
      in terms of service design.

PMID- 22467562
TI  - Surgical outcome of ileal pouch-anal anastomosis when used intentionally for well
      defined Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is considered a contraindication to ileal pouch-
      anal anastomosis (IPAA). In this study, we compare outcomes of CD and ulcerative
      colitis (UC) patients undergoing IPAA. METHODS: Patients were considered to have
      CD before surgery based on a history of small bowel disease, perianal disease,
      noncrypt-associated granuloma, or pretreatment skip colonic lesions. Patients
      were prospectively assessed for pouchitis or CD. Postoperative CD (pouch
      inflammation into the afferent limb or pouch fistula) or pouch failure (need for
      permanent diversion) were assessed. Preoperative serum was assayed for IBD
      associated antibodies using enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Seventeen patients with preoperative CD were identified. Seven (41%) patients
      developed postoperative recurrent CD in the afferent limb (n = 3) or pouch
      fistulizing disease (n = 4). One patient (6%) required pouch excision. The
      incidence of postoperative CD was higher (P = 0.002) in preoperative CD patients
      (41%) than UC patients (11%). There was no significant difference in pouchitis or
      pouch failure. There was also no significant difference in any preoperative
      clinical feature between patients with or without postoperative CD. Afferent limb
      inflammation developed in three (50%) of the six patients with pANCA+/OmpC-
      expression compared to none of the 11 patients without this serologic profile (P
      = 0.03). CONCLUSIONS: Although the intentional use of IPAA in CD has a higher
      incidence of postoperative disease vs. UC patients, there was no significant
      difference in pouch failure. Demographics, clinical features, and serologic
      factors do not predict outcome of CD patients undergoing IPAA. IBD serology may
      identify the phenotype manifestation of postoperative recurrent CD.

PMID- 22467563
TI  - Integrating asthma education and smoking cessation for parents: financial return
      on investment.
AB  - BACKGROUND: Caregivers who smoke and have children with asthma are an important
      group for intervention. Home-based interventions successfully reduce asthma
      morbidity, yet are costly. This study evaluated the financial return on
      investment (ROI) of the Parents of Asthmatics Quit Smoking (PAQS) program, a
      combined asthma education and smoking cessation intervention. METHODS:
      Participants included caregivers (n = 224) that smoked, had a child with asthma,
      and were enrolled in a Medicaid managed care plan. Participants received nurse
      delivered asthma education and smoking counseling in three home visits. Program
      implementation costs were estimated, and healthcare expenses were obtained from
      insurance claims data 12 months pre- and 12 months post intervention. ROI was
      calculated for all participants, children <6 years, children 6-18 years, and
      children with moderate/severe persistent asthma. RESULTS: Total program
      implementation cost was $34,481. After intervention, there was increased mean
      annual refills of beta-agonist (0.51 pre, 1.64 post; P < 0.001), and controller
      medications (0.65 pre, 2.44 post; P < 0.001). Reductions were found in mean
      annual emergency department visits (0.33 pre, 0.14 post; P < 0.001),
      hospitalizations (0.23 pre, 0.08 post; P < 0.001), and outpatient visits (2.33
      pre, 1.45 post, P < 0.001). The program had negative ROI (-21.8%) for the entire
      sample. The ROI was positive (+106.9) for children <6 years, negative (-150.3)
      for children 6-18, and negligible for moderate/severe persistent asthma (+6.9%).
      CONCLUSION: PAQS was associated with increased medication use and decreased
      healthcare utilization. While the overall ROI for PAQS was negative, PAQS had a
      positive ROI for caregivers of young children with asthma.

PMID- 22467564
TI  - Rho GTPase signaling in the development of colorectal cancer.
AB  - The involvement of Rho GTPases in major aspects of cancer development, such as
      cell proliferation, apoptosis, cell polarity, adhesion, migration, and invasion,
      have recently been attracting increasing attention. In this review, we have
      summarized the current findings in the literature, and we discuss the
      participation of the Rho GTPase members RhoA, Rac1, and Cdc42 in the development
      of colorectal cancer, the second most lethal neoplasia worldwide. First, we
      present an overview of the mechanisms of Rho GTPase regulation and the impact
      that regulator proteins exert on GTPase signaling. Second, we focus on the
      participation of Rho GTPases as modulators of colorectal cancer development.
      Third, we emphasize the involvement of activation and expression alterations of
      Rho GTPases in events associated with cancer progression, such as loss of cell
      cell adhesion, proliferation, migration, and invasion. Finally, we highlight the
      potential use of novel anticancer drugs targeting specific components of the Rho
      GTPase signaling pathway with antineoplastic activity in this cancer type.

PMID- 22467565
TI  - Broadband excitation pulses for high-field solid-state nuclear magnetic resonance
      spectroscopy.
AB  - In nuclear magnetic resonance spectroscopy, experimental limits due to the
      radiofrequency transmitter and/or coil means that conventional radiofrequency
      pulses ("hard pulses") are sometimes not sufficiently powerful to excite
      magnetization uniformly over a desired range of frequencies. Effects due to
      nonuniform excitation are most frequently encountered at high magnetic fields for
      nuclei with a large range of chemical shifts. Using optimal control theory, we
      have designed broadband excitation pulses that are suitable for solid-state
      samples under magic-angle-spinning conditions. These pulses are easy to
      implement, robust to spinning frequency variations, and radiofrequency
      inhomogeneities, and only four times as long as a corresponding hard pulse. The
      utility of these pulses for uniformly exciting (13) C nuclei is demonstrated on a
      900 MHz (21.1 T) spectrometer.

PMID- 22467566
TI  - Long-range heteronuclear coupling constants in 2,6-disubstituted purine
      derivatives.
AB  - Four- and five-bond heteronuclear J-couplings between the hydrogen H-8 and
      carbons C-6 and C-2 in a series of 7- and 9-benzyl substituted purine derivaties
      with variuous substituents in positions 2 and 6 were studied by coupled (13)  C
      NMR and H,C-HMBC experiments and by DFT calculations. We have found that for some
      of the derivatives, the five-bond coupling H8-C2 is higher than the four-bond H8
      C6 coupling, which is also evidenced by a stronger crosspeak in the HMBC. This
      finding contradicts the generally accepted opinion that only strong three-bond
      crosspeaks and one weak four-bond H8-C6 crosspeak can be observed in the HMBC
      spectra of purine derivatives. The misinterpretation of HMBC spectra may lead to
      an incorrect determination of the purine derivatives' structure.

PMID- 22467567
TI  - Prevalence of dental features that indicate a need for early orthodontic
      treatment.
AB  - The aim of the study was to establish the prevalence of dental features that
      indicate a need for early orthodontic treatment (EOT). A group of schoolchildren
      in the mixed dentition stage (7-11 years old) (n = 432) was clinically screened
      for indications for EOT. Over 1/3 of the youngsters (34.7 per cent) presented at
      least one of the indications for EOT: anterior and posterior crossbites
      (including edge to edge occlusion) were found in 9.5 and 23.3 per cent,
      respectively; Angle Class III was found in 3 per cent; increased overjet (>=7 mm)
      prevailed in 3.7 per cent and was significantly related to risk for dental trauma
      (P = 0.001); while oral habits were practiced by 10.9 per cent, open bite was
      found only in 6.5 per cent, both predominantly among girls (P = 0.006 and P =
      0.012, respectively); impinging overbite was present in 5.2 per cent, mainly in
      boys (P = 0.006); crowding >5 mm was found in 6.9 per cent for the maxilla and in
      6 per cent for the mandible. Loss of tooth material affecting tooth position was
      found in 15.3 per cent. Normal occlusal relationships were found in 10.9 per cent
      only. The findings indicate that almost 1/3 of the examined children in the mixed
      dentition stage require EOT. Sexual dimorphism was demonstrated for several
      occlusal features. 

PMID- 22467568
TI  - The association of tongue posture with the dentoalveolar maxillary and mandibular
      morphology in Class III malocclusion: a controlled study.
AB  - The aim of the present study was to evaluate the association of tongue posture
      with the dentoalveolar maxillary and mandibular morphology in a group of Class
      III subjects in comparison to a group of Class I subjects. Twenty Class III
      subjects (9 males, 11 females, 19.2 +/- 4.6 years) and 20 Class I subjects (6
      males, 14 females, 17.4 +/- 1.7 years) were included in the present study.
      Maxillary and mandibular morphology was defined by the intermolar and intercanine
      distances, at both the cusps and gingival levels, and by measuring surface area
      and volume of the palatal vault and mouth floor assessed on three-dimensional
      digital models. Tongue-to-palate distances were measured on lateral cephalograms.
      The groups were compared using the Mann-Whitney U-test and correlations between
      each morphological parameter and the tongue-to-palate distances were calculated
      using the Spearman correlation coefficient. The mandibular intermolar width at
      the gingival level was significantly greater in the Class III group (P < 0.01),
      while the maxillary intercanine widths were significantly smaller in the Class
      III group (P < 0.05). The mouth floor area and volume and the respective ratios
      between the mouth floor and palate were significantly greater in the Class III
      group (P = 0.01). The tongue-to-palate distances were generally greater, i.e.
      lower tongue posture, for the Class III subjects. Significant correlations were
      seen between tongue-to-palate distances in the posterior region with the area
      ratio (rho = 0.44, P < 0.05). Tongue posture is significantly lower in Class III
      subjects and is associated with the dentoalveolar characteristics of the maxilla
      and mandible.

PMID- 22467569
TI  - Altered serum levels of the osteoclast-specific TRACP 5b isoform in Chinese
      children undergoing orthodontic treatment.
AB  - Orthodontic tooth movement is dependent upon the ability of mechanical forces to
      induce remodelling activity within the tooth-supporting alveolar bone. In view of
      the importance of bone resorption in mediating tooth movement, the aim of this
      study was to establish if alterations in the osteoclast-specific bone marker
      tartrate-resistant acid phosphatase (TRACP) 5b could be detected in the sera of
      patients undergoing orthodontic treatment. The sample consisted of 14 subjects
      (10 girls and 4 boys) aged 10.5-16.5 years (mean 12.6 years) being treated with
      fixed appliances and a distalizing headgear. Venous blood samples (3 ml) were
      collected from the cubital vein pre-treatment (T0) and 2, 4, and 6 months into
      treatment (T1-T3); serum TRACP 5b levels were quantified using a solid-phase
      immunofixed enzyme activity assay. When the data were pooled and treated cross
      sectionally, a significant increase in immunoreactive TRACP 5b was detected at 2
      months (T1) indicating increased bone resorptive activity. However, when the
      serum profiles of individual patients were recorded longitudinally, a very
      different pattern emerged, not all patients following the same trend. This is not
      surprising given normal anatomical variation and differences between the patients
      in age, gender, and mechanotherapy. Designed as a pilot to demonstrate 'proof of
      principle', this study is the first to show that the TRACP 5b isoform can be
      detected in the sera of patients undergoing orthodontic treatment. It further
      suggests that serum bone marker measurements offer a simple and minimally
      invasive method for correlating the findings of laboratory and animal
      experimentation with clinical data.

PMID- 22467570
TI  - Analysis of human adenovirus type 19 associated with epidemic
      keratoconjunctivitis and its reclassification as adenovirus type 64.
AB  - PURPOSE: Human adenovirus species D type 19 (HAdV-D19) has been associated with
      epidemic keratoconjunctivitis (EKC), a highly inflammatory infection of the
      ocular surface. Confusion exists regarding the origins of HAdV-D19. The prototype
      virus (HAdV-D19p) does not cause EKC, while a virus identified later with the
      identical serologic determinant is a significant ocular pathogen. METHODS: High
      throughput genome sequencing and bioinformatics analysis were performed on HAdV
      D19p and three HAdV-D19 EKC strains, and compared to the previously sequenced
      clinical isolate, HAdV-D19 (C) and HAdV-D37. Corneas of C57BL/6J mice were
      injected with HAdV-D19p, HAdV-D19 (C), or virus-free buffer, and inflammation
      assessed by clinical examination, flow cytometry, and cytokine ELISA. Confocal
      microscopy and real-time PCR of infected corneal cell cultures were used to test
      viral entry. RESULTS: HAdV-D19 (C) and the other clinical EKC isolates showed
      nearly 100% sequence identity. EKC strains diverged from HAdV-D19p in the penton
      base, E3, and fiber transcription units. Simplot analysis showed recombination
      between EKC-associated HAdV-D19 with HAdV-D37, HAdV-D22, and HAdV-D19p, the
      latter contributing only the hexon gene, the principal serum neutralization
      determinant. HAdV-D19p induced stromal keratitis in the C57BL/6J mouse, but
      failed to infect productively human corneal epithelial cells. These data led to
      retyping of the clinical EKC isolates with a HAdV-D19 hexon gene as HAdV-D64.
      CONCLUSIONS: HAdV-D19 associated with EKC (HAdV-D64) originated from a
      recombination between HAdV-D19p, HAdV-D37, and HAdV-D22, and was mischaracterized
      because of a shared hexon gene. HAdV-D19p is not infectious for corneal
      epithelial cells, thus explaining the lack of any association with keratitis.

PMID- 22467571
TI  - Automated quantification of optic nerve axons in primate glaucomatous and normal
      eyes--method and comparison to semi-automated manual quantification.
AB  - PURPOSE: To describe an algorithm and software application (APP) for 100% optic
      nerve axon counting and to compare its performance with a semi-automated manual
      (SAM) method in optic nerve cross-section images (images) from normal and
      experimental glaucoma (EG) nonhuman primate (NHP) eyes. METHODS: ON cross
      sections from eight EG eyes from eight NHPs, five EG and five normal eyes from
      five NHPs, and 12 normal eyes from 12 NHPs were imaged at 100*. Calibration (n =
      500) and validation (n = 50) image sets ranging from normal to end-stage damage
      were assembled. Correlation between APP and SAM axon counts was assessed by
      Deming regression within the calibration set and a compensation formula was
      generated to account for the subtle, systematic differences. Then, compensated
      APP counts for each validation image were compared with the mean and 95%
      confidence interval of five SAM counts of the validation set performed by a
      single observer. RESULTS: Calibration set APP counts linearly correlated to SAM
      counts (APP = 10.77 + 1.03 [SAM]; R(2) = 0.94, P < 0.0001) in normal to end-stage
      damage images. In the validation set, compensated APP counts fell within the 95%
      confidence interval of the SAM counts in 42 of the 50 images and were within 12
      axons of the confidence intervals in six of the eight remaining images.
      Uncompensated axon density maps for the normal and EG eyes of a representative
      NHP were generated. CONCLUSIONS: An APP for 100% ON axon counts has been
      calibrated and validated relative to SAM counts in normal and EG NHP eyes.

PMID- 22467572
TI  - Nanoparticle-mediated delivery of shRNA.VEGF-a plasmids regresses corneal
      neovascularization.
AB  - PURPOSE: To determine the efficacy of a plasmid containing a small hairpin RNA
      expression cassette (pSEC.shRNA) against VEGF-A-loaded poly(lactic co-glycolic
      acid) nanoparticles (PLGA NPs) in the sustained regression of murine corneal
      neovascularization. METHODS: PLGA nanoparticles were loaded with pSEC.shRNA.VEGF
      A plasmids using the double emulsion-solvent evaporation method. KNV was induced
      in BALB/c mice by mechanical-alkali injury. Four weeks after induction of KNV,
      the mice were randomly divided to receive one of four treatments intrastromally:
      pSEC.shRNA.VEGF-A PLGA NPs (2 MUg plasmid); naked pSEC.shRNA.VEGF-A plasmid only
      (2 MUg plasmid); control blank PLGA NPs (equivalent dry weight of NPs); and
      vehicle. Two and five days after intervention, corneas were harvested to
      determine VEGF-A gene and protein expression using reverse transcriptase
      polymerase chain reaction and ELISA, respectively. Four weeks after intervention,
      corneas were photographed, mice sacrificed, and the corneal whole mounts were
      immunostained for CD31 (panendothelial cell marker). Immunofluorescence
      microscopy was performed and the neovascular area was quantitated. RESULTS: VEGF
      A mRNA (49.6 +/- 12.4 vs. 82.9 +/- 6.0%, P < 0.01) and protein (4.0 +/- 5.2 vs.
      20.0 +/- 7.5 rhog VEGF-A/mg total protein, P < 0.05) expression were
      significantly reduced in pSEC.shRNA.VEGF-A PLGA NP-treated corneas as compared
      with control blank NP. The pSEC.shRNA.VEGF-A PLGA NP-treated corneas showed
      significant regression in the mean fractional areas of KNV (0.125 +/- 0.042;
      12.5%, P <0.01) compared with both naked plasmid only (0.283 +/- 0.004; 28.3%)
      and control (blank NPs = 0.555 +/- 0.072, 55.5%) at 4 weeks post-treatment.
      CONCLUSIONS: The pSEC.shRNA.VEGF-A-loaded PLGA NPs are an effective, nonviral,
      nontoxic, and sustainable form of gene therapy for the regression of murine KNV.

PMID- 22467573
TI  - Neuronal NAD(P)H oxidases contribute to ROS production and mediate RGC death
      after ischemia.
AB  - PURPOSE: To study the role of neuronal nicotinamide adenine dinucleotide
      phosphate [NAD(P)H] oxidase-dependent reactive oxygen species (ROS) production in
      retinal ganglion cell (RGC) death after ischemia. METHODS: Ischemic injury was
      induced by unilateral elevation of intraocular pressure via direct corneal
      cannulation. For in vitro experiments, RGCs isolated by immunopanning from
      retinas were exposed to oxygen and glucose deprivation (OGD). The expression
      levels of NAD(P)H oxidase subunits were evaluated by quantitative PCR,
      immunocytochemistry, and immunohistochemistry. The level of ROS generated was
      assayed by dihydroethidium. The NAD(P)H oxidase inhibitors were then tested to
      determine if inhibition of NAD(P)H oxidase altered the production of ROS within
      the RGCs and promoted cell survival. RESULTS: It was reported that RGCs express
      catalytic Nox1, Nox2, Nox4, Duox1, as well as regulatory Ncf1/p47phox,
      Ncf2/p67phox, Cyba/p22phox, Noxo1, and Noxa1 subunits of NAD(P)H oxidases under
      normal conditions and after ischemia. However, whereas RGCs express only low
      levels of catalytic Nox2, Nox4, and Duox1, and regulatory Ncf1/p47, Ncf2/p67
      subunits, they exhibit significantly higher levels of catalytic subunit Nox1 and
      the subunits required for optimal activity of Nox1. It was observed that the
      nonselective NAD(P)H oxidase inhibitors VAS-2870, AEBSF, and the Nox1 NAD(P)H
      oxidase-specific inhibitor ML-090 decreased the ROS burst stimulated by OGD,
      which was associated with a decreased level of RGC death. CONCLUSIONS: The
      findings suggest that NAD(P)H oxidase activity in RGCs renders them vulnerable to
      ischemic death. Importantly, high levels of Nox1 NAD(P)H oxidase subunits in RGCs
      suggest that this enzyme could be a major source of ROS in RGCs produced by
      NAD(P)H oxidases.

PMID- 22467574
TI  - Role of histamine and its receptor subtypes in stimulation of conjunctival goblet
      cell secretion.
AB  - PURPOSE: The purpose of this study was to determine the effect of histamine and
      its receptors on goblet cell secretion. METHODS: Cultured rat and human goblet
      cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight
      glycoconjugate was measured by an enzyme-linked lectin assay. Cultured rat goblet
      cells were homogenized and either RNA was isolated for RT-PCR or proteins were
      isolated for Western blot analysis for presence of histamine receptors subtypes
      H1 through H4. The localization of these receptors was determined in rat and
      human goblet cells by immunofluorescence microscopy. RESULTS: Histamine
      stimulated goblet cell secretion in a concentration- and time-dependent manner.
      All four histamine receptors were present in cultured rat and human goblet cells.
      Use of agonists specific to individual histamine receptor subtypes indicated that
      the rank order of agonist stimulation was H1 = H3 > H4 > H2. Using antagonists
      specific to individual histamine receptor subtypes determined that H2 and H3, but
      not the H1 and H4, antagonists, inhibited histamine-stimulated conjunctival
      goblet cell secretion. CONCLUSIONS: Rat and human conjunctival goblet cells are a
      direct target of histamine, which induces secretion. All four histamine receptors
      are present in rat and human conjunctiva and are active in rat conjunctival
      goblet cells. These findings suggest that all four histamine receptor subtypes
      are important for conjunctival goblet cell secretion. Blockage of histamine
      receptor subtypes could prevent the excess mucus production associated with
      ocular allergy.

PMID- 22467575
TI  - Compound 49b prevents diabetes-induced apoptosis through increased IGFBP-3
      levels.
AB  - PURPOSE: To determine whether Compound 49b, a novel PKA-activating drug, can
      prevent diabetic-like changes in the rat retina through increased insulin-like
      growth factor binding protein-3 (IGFBP-3) levels. METHODS: For the cell culture
      studies, we used both human retinal endothelial cells (REC) and retinal Muller
      cells in either 5 mM (normal) or 25 mM (high) glucose. Cells were treated with 50
      nM Compound 49b alone of following treatment with protein kinase A (PKA) siRNA or
      IGFBP-3 siRNA. Western blotting and ELISA analyses were done to verify PKA and
      IGFBP-3 knockdown, as well as to measure apoptotic markers. For animal studies,
      we used streptozotocin-treated rats after 2 and 8 months of diabetes. Some rats
      were treated topically with 1 mM Compound 49b. Analyses were done for retinal
      thickness, cell numbers in the ganglion cell layer, pericyte ghosts, and numbers
      of degenerate capillaries, as well as electroretinogram and heart morphology.
      RESULTS: Compound 49b requires active PKA and IGFBP-3 to prevent apoptosis of
      REC. Compound 49b significantly reduced the numbers of degenerate capillaries and
      pericyte ghosts, while preventing the decreased retinal thickness and loss of
      cells in the ganglion cell layer. Compound 49b maintained a normal
      electroretinogram, with no changes in blood pressure, intraocular pressure, or
      heart morphological changes. CONCLUSIONS: Topical Compound 49b is able to prevent
      diabetic-like changes in the rat retina, without producing systemic changes.
      Compound 49b is able to prevent REC apoptosis through increasing IGFBP-3 levels,
      which are reduced in response to hyperglycemia.

PMID- 22467577
TI  - Eye vessel compliance as a function of intraocular and arterial pressure and eye
      compliance.
AB  - PURPOSE: The purpose of our study is to develop and validate a methodology to
      measure the compliance of the vascular network in the eye using biomechanical
      parameters, namely arterial pressure, intraocular pressure (IOP), and ocular
      compliance of the eyeball (OC). METHODS: In vitro experiments were conducted on 6
      freshly enucleated rabbit eyes. An inflatable catheter was inserted in the
      posterior chamber. The balloon was inflated and its volume changed periodically
      at a rate of 1-2 Hz, yielding variations in the intraocular volume; thus,
      emulating the volume pulsations of the vascular network in the eye. The IOP was
      measured continuously with a pressure transducer and the OC was calculated using
      the outflow facility. The compliance of the balloon, mimicking the compliance of
      the vascular network, was estimated indirectly from the measurements of IOP,
      balloon pressure, and OC. The estimated balloon compliance was compared to direct
      estimates of balloon compliance, based on the balloon pressure-volume curve. In
      vivo study included 5 white New-Zealand rabbits. The method to estimate the
      vascular compliance of the eye was tested under normal conditions and after
      administration of norepinephrine, which induced a vasoconstriction leading to
      reduction in vascular compliance. RESULTS: In vitro comparison of direct versus
      indirect estimates of compliance showed a difference that was not significant
      (0.075 vs. 0.077 MUL/mm Hg, P = 0.86). Results from the in vivo study indicated
      that norepinephrine significantly increased the arterial pulse pressure
      amplitude, while compliance of vascular network of the eye decreased from 0.18 +/
      0.12 to 0.10 +/- 0.08 MUL/mm Hg (P = 0.001). CONCLUSIONS: The eye vascular
      compliance can be predicted using the IOP, arterial pressure, and OC of the
      eyeball.

PMID- 22467576
TI  - Retinoid content, visual responses, and ocular morphology are compromised in the
      retinas of mice lacking the retinol-binding protein receptor, STRA6.
AB  - PURPOSE: We report generation of a mouse model in which the STRA6 gene has been
      disrupted functionally to facilitate the study of visual responses, changes in
      ocular morphology, and retinoid processing under STRA6 protein deficiency.
      METHODS: A null mouse line, stra6 -/-, was generated. Western Blot and
      immunocytochemistry were used to determine expression of STRA6 protein. Visual
      responses and morphological studies were performed on 6-week, 5-month and 10
      month-old mice. The retinoid content of eye tissues was evaluated in dark-adapted
      mice by high performance liquid chromatography. RESULTS: STRA6 protein was not
      detectable in stra6 -/- null mice, which had a consistent reduction, but not
      total ablation of their visual responses. The mice also showed significant
      depletion of their retinoid content in retinal pigment epithelium (RPE) and
      neurosensory retina, including a 95% reduction in retinyl esters. At the
      morphological level, a reduction in thickness of the neurosensory retina due to
      shortening of the rod outer and inner segments was observed when compared to
      control litter mates with a commensurate reduction in rod a- and b-wave
      amplitudes. In addition, there was a reduction in cone photoreceptor cell number
      and cone b-wave amplitude. A typical hallmark in stra6 -/- null eyes was the
      presence of a persistent primary hypertrophic vitreous, an optically dense
      vascularized structure located in the vitreous humor between the posterior
      surface of the lens and neurosensory retina. CONCLUSIONS: Our studies of stra6 -/
      null mice established the importance of the STRA6 protein for the uptake,
      intracellular transport, and processing of retinol by the RPE. In its absence,
      rod photoreceptor outer and inner segment length was reduced, and cone cell
      numbers were reduced, as were scotopic and photopic responses. STRA6 also was
      required for dissolution of the primary vitreous. However, it was clear from
      these studies that STRA6 is not the only pathway for retinol uptake by the RPE.

PMID- 22467578
TI  - Cell swelling contributes to thickening of low-dose N-methyl-D-aspartate-induced
      retinal edema.
AB  - PURPOSE: The contribution of cell swelling versus vascular leakage in retinal
      edema remains largely undefined. The objective of this study was to use in vivo
      magnetic resonance imaging (MRI) to assess retinal cell swelling in the edematous
      mouse retina. METHODS: Inner retinal edema was induced by intravitreal injection
      of 2.5 nmol N-methyl-D-aspartate (NMDA). To assess retinal cell swelling,
      diffusion MRI was performed at baseline, 3-hours, 1 day, 3 days, and 7 days (n >=
      5 at each time point) after NMDA injection. To detect retinal vascular leakage,
      gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced MRI was
      performed at baseline, 3 hours and 1 day (n = 5 for each group) after NMDA
      injection. Upon the completion of MRI, mouse eyes were enucleated, cryosectioned,
      and stained for assessing retinal layer thickness and cell death. RESULTS: Inner
      retinal cell swelling was hyperintense on diffusion-weighted images at 3 hours
      and 1 day after NMDA injection. The thickened inner retina was also seen in
      anatomic MRI and histology. Quantitatively, inner retinal apparent diffusion
      coefficient (ADC) decreased approximately 20% at 3 hours and 1 day after NMDA
      injection (P < 0.05 compared with baseline), suggesting cell swelling. Systematic
      injection of paramagnetic Gd-DTPA did not alter vitreous longitudinal relaxation
      time (T1) at baseline or at 3 hours after NMDA injection. In contrast, vitreous
      T1 in mice decreased 16 +/- 6% (P < 0.05), reflecting retinal vascular leakage at
      1 day after NMDA injection. CONCLUSIONS: Noninvasive diffusion MRI was performed
      to detect retinal cell swelling in vivo. Our results demonstrated that retinal
      cell swelling could directly lead to retinal thickening independent of vascular
      leakage.

PMID- 22467579
TI  - Improved estimates of visual field progression using bayesian linear regression
      to integrate structural information in patients with ocular hypertension.
AB  - PURPOSE: To assess whether neuroretinal rim area (RA) measurements of the optic
      disc could be used to improve the estimate of the rate of change in visual field
      (VF) mean sensitivity in patients with ocular hypertension (OHT) using a Bayesian
      linear regression (BLR), compared to a standard ordinary least squares linear
      regression (OLSLR) of mean sensitivity (MS) measurements alone. METHODS: MS and
      RA measurements were analyzed from a longitudinal series of 179 patients with OHT
      visiting Moorfields Eye Hospital between 1992 and 2000. For each patient, linear
      regression of RA was computed after an appropriate transformation to "scale" RA
      with MS measurements, and the slope coefficient from this regression was used as
      a prior for BLR of MS. The BLR then was compared with the OLSLR approach by
      evaluating how accurately each regression technique predicted future MS
      measurements. RESULTS: On average, BLR was significantly more accurate than OLSLR
      for series up to 8 measurements long (root-mean-square prediction error [RMSPE]
      was 0.14 decibels [dB] smaller with BLR than OLSLR; P < 0.001, Wilcoxon signed
      rank test), with OLSLR of VF data alone being more accurate for longer series
      (RMSPE was 0.06 dB smaller with OLSLR than BLR). CONCLUSIONS: BLR provides a
      significantly more accurate estimate of the rate of change in MS than the
      standard OLSLR approach, especially in short time series, suggesting that
      structural measurements can be used successfully in statistical models to assist
      clinicians monitoring VF progression in patients with OHT. Further studies are
      necessary to validate the method in glaucoma patients.

PMID- 22467581
TI  - The effect of central visual impairment on manual prehension when tasked with
      transporting-to-place an object accurately to a new location.
AB  - PURPOSE: To investigate whether differences exist between visually impaired and
      normal vision participants when completing a visually guided manual prehension
      task of transporting-to-place an object accurately to a new location. METHODS:
      Participants with central visual impairment (n = 17) and normal vision (n = 10)
      were tasked with reaching-to-grasp an object and then transporting-to-place it
      accurately to a different (predefined) location. Analysis assessed movements of
      the object transport phase and error in object placement. Correlation analysis
      assessed the association between the movements and mean loss in the central 5
      degrees , 10 degrees , and 20 degrees  of participant's integrated binocular
      visual field (VF), visual acuity (VA), and contrast sensitivity (CS). Results.
      Compared to normal vision participants, visually impaired participants took
      significantly longer to complete the movement and exhibited increased
      deceleration time, greater number of velocity corrections, and more errors in
      object placement (P < 0.05). Findings demonstrated that participants with central
      visual impairment were more cautious when executing the movement, which
      contributed to uncertainty regarding end-position location. A higher number of
      movement indices were correlated with loss in the central 5 degrees  compared to
      the 10 degrees  and 20 degrees  of the VF. VA and CS were significantly
      correlated with a number of movement variables. CONCLUSIONS: Despite the
      increased time taken by visually impaired participants to complete the task, they
      were still less accurate than normals when placing the object. Decrements in
      movement control were most associated with loss in the central 5 degrees  when
      compared to the central 10 degrees  and 20 degrees  of the VF, which was
      evidenced in the deceleration/"online" component of the movement.

PMID- 22467580
TI  - Quantitative assessment of ultrastructure and light scatter in mouse corneal
      debridement wounds.
AB  - PURPOSE: The mouse has become an important wound healing model with which to
      study corneal fibrosis, a frequent complication of refractive surgery. The aim of
      the current study was to quantify changes in stromal ultrastructure and light
      scatter that characterize fibrosis in mouse corneal debridement wounds. METHODS:
      Epithelial debridement wounds, with and without removal of basement membrane,
      were produced in C57BL/6 mice. Corneal opacity was measured using optical
      coherence tomography, and collagen diameter and matrix order were quantified by x
      ray scattering. Electron microscopy was used to visualize proteoglycans.
      Quantitative PCR (Q-PCR) measured mRNA transcript levels for several quiescent
      and fibrotic markers. RESULTS: Epithelial debridement without basement membrane
      disruption produced a significant increase in matrix disorder at 8 weeks, but
      minimal corneal opacity. In contrast, basement membrane penetration led to
      increases in light scatter, matrix disorder, and collagen diameter, accompanied
      by the appearance of abnormally large proteoglycans in the subepithelial stroma.
      This group also demonstrated upregulation of several quiescent and fibrotic
      markers 2 to 4 weeks after wounding. CONCLUSIONS: Fibrotic corneal wound healing
      in mice involves extensive changes to collagen and proteoglycan ultrastructure,
      consistent with deposition of opaque scar tissue. Epithelial basement membrane
      penetration is a deciding factor determining the degree of ultrastructural
      changes and resulting opacity.

PMID- 22467582
TI  - Factors associated with anterior chamber narrowing with age: an optical coherence
      tomography study.
AB  - PURPOSE: The purpose of our study is to evaluate the effect of age on various
      anterior segment (AS) parameters in healthy eyes using AS optical coherence
      tomography (OCT), and to examine their relationship to anterior chamber angle
      (ACA) narrowing with age. METHODS: A total of 388 consecutive Korean subjects
      aged 30 to 89 years was imaged by AS OCT. Anterior chamber depth (ACD), iris
      cross-sectional area (IA), iris thickness at 750 and 1500 MU from the scleral
      spur (IT(750, 1500)), iris curvature (IC), lens vault (LV), and anterior chamber
      area (AA) were determined using Image J software (version 1.44). The absolute and
      normalized slopes of these parameters, adjusted for axial length and sex, were
      determined by linear mixed-effects modeling. Multivariate regression analysis was
      performed to evaluate factors associated with ACA narrowing, which was defined as
      the angle-opening distance (AOD(500)) at the temporal angle. RESULTS: ACD and AA
      had significantly negative slopes (-0.0119 mm/year, -0.0845 mm(2)/year, P <
      0.0001, <0.0001) with age, and LV, IC, IT(750), IT(1500), and IA had
      significantly positive slopes (0.0084 mm/year, 0.0019 mm/year, 0.0006 mm/year,
      0.0008 mm/year, 0.0131 mm(2)/year, all P < 0.05). IC, ACD, LV, and AA underwent
      the greatest changes when analyzed by normalized slopes. IC, LV, age, and axial
      length were associated significantly with ACA narrowing (all P < 0.0001).
      CONCLUSIONS: Increments of LV, IC, IT, and IA with age led to a reduction in the
      dimensions of the AC and to narrowing of the ACA. This may explain why aging is a
      significant risk factor for primary angle closure glaucoma.

PMID- 22467583
TI  - Isoforms of secretory group two phospholipase A (sPLA2) in mouse ocular surface
      epithelia and lacrimal glands.
AB  - PURPOSE: To compare and contrast the distribution patterns of select secretory
      group two phospholipase A (sPLA2) isoforms in corneal epithelia (CN),
      conjunctival epithelia (CNJ), and lacrimal glands (LG) of BALB/c and C57BL/6
      mice. METHODS: Gene expression of select sPLA2 isoforms was quantified via real
      time reverse-transcription PCR (qRT(2)-PCR). Immunofluorescence assay (IFA) of
      the sPLA2-IIa, -V, and -X isoforms were used to confirm qRT(2)-PCR results. sPLA2
      IIa function was confirmed via in vitro CN and CNJ culturing. RESULTS: qRT(2)-PCR
      revealed that sPLA2 isoforms (pla2g5, 12a, and 12b), cPLA2 isoform (pla2g4a),
      iPLA2 isoform (pla2g6), and PLA2-receptor (pla2r1) were present in all tissues of
      both strains, whereas sPLA2 isoforms (pla2g1b, 2e, and 3) were absent. sPLA2
      isoforms (pla2g2a, 2d, 2f, and 10) showed tissue- and strain-specific expression:
      2a in BALB/c CNJ only; 2d at higher levels in CNJ than LG; and 2f and 10 in CN
      and CNJ, but absent in LG. Upon dry eye (DE) induction, pla2g2a, 2d, and 2f were
      upregulated in BALB/c CNJ, and 10 was absent from CN. Furthermore, BALB/c DE mice
      showed upregulation of pla2r1 in CN and CNJ and downregulation of 12a and 12b in
      LG. IFA of sPLA2-IIa, -V, and -X in DE CNJ confirmed the upregulation of pla2g2a,
      5, and 10. Last, in vitro CN and CNJ culturing confirmed that sPLA2-IIa amplifies
      ocular surface inflammation in CNJ but not in CN. CONCLUSIONS: sPLA2 isoforms
      exhibit differential expression patterns when comparing BALB/c with C57BL/6 mice;
      and DE with control BALB/c mice. These findings suggest that at least some sPLA2
      isoforms must have significant roles in ocular surface physiology and
      inflammation.

PMID- 22467584
TI  - A model of corneal graft rejection in semi-inbred NIH miniature swine:
      significant T-cell infiltration of clinically accepted allografts.
AB  - PURPOSE: The purpose of our study is to develop a pre-clinical model of corneal
      graft rejection in the semi-inbred NIH minipig as a model of human rejection.
      METHODS: NIH minipigs received corneal allografts with MHC and minor mismatches,
      or minor mismatches alone. Clinical rejection was monitored, and major subsets of
      leukocytes and ingress of vessels were quantified post-mortem by automated
      digital methods. Spectratypes of recipient T-cell receptor beta-subunit variable
      region (TRbetaV) were analyzed. The capacity of pig corneal endothelial cells to
      proliferate in vivo was assessed. RESULTS: Autografts (n = 5) and SLA(cc) to
      SLA(cc) allografts (minor mismatches, n = 5) were not rejected. Median graft
      survival of SLA(dd) and SLA(bb) allografts in SLA(cc) strain recipients (major
      and minor mismatches) was 57 (n = 10) and 67 (n = 6) days, respectively. Rejected
      grafts did not recover clarity in vivo, and corneal endothelial cells did not
      proliferate in organ culture after cryo-injury. There were significantly more
      leukocytes in clinically rejected versus accepted grafts (P < 0.0001) and in
      transplanted versus contralateral eyes (P < 0.0001). Numbers of T-cells were
      significantly greater in clinically accepted grafts versus autografts and in
      rejected grafts versus accepted (P < 0.005 for most subsets). There were
      significant differences in TRbetaV spectratype between graft groups in cornea,
      but not in draining lymph node or blood (P < 0.05). CONCLUSIONS: The NIH minipig
      offers a robust model of human rejection suitable for immunological or
      therapeutic studies. In particular, there is limited capacity for corneal
      endothelial repair in vivo, and histological evidence suggests that
      allosensitization of the recipient may develop in the absence of clinical
      rejection.

PMID- 22467585
TI  - Imaging of retinal whitening in retinal vein occlusion may shed light on malarial
      retinopathy.

PMID- 22467586
TI  - Treatment of multilevel macular hemorrhage secondary to retinal arterial
      macroaneurysm with submacular tissue plasminogen activator.
AB  - PURPOSE: To evaluate the efficacy of pars plana vitrectomy (PPV) followed by
      internal limiting membrane (ILM) removal and injection of subretinal recombinant
      tissue plasminogen activator (rtPA)-assisted pneumatic displacement in eyes with
      massive multilevel macular hemorrhage caused by ruptured retinal arterial
      macroaneurysm (RAMA). METHODS: Four eyes of 4 patients treated with PPV for
      recent (</= 7 days) macular hemorrhage at both beneath the ILM and subretinal
      space involving the center of the fovea caused by RAMA were included in the
      study. In each case, following PPV, ILM removal, subretinal injection of rtPA
      (12.5 ug/0.1 mL), and fluid-air exchange with postoperative prone positioning was
      performed. Optical coherence tomography (OCT) examination was performed at the
      initial and the follow-up visits. RESULTS: Duration of symptoms ranged from 3 to
      7 days (average, 4.5+/-1.9 days). Preoperative visual acuity ranged from hand
      motions to 20/800. Follow-up ranged from 6 to 18 months (average, 13+/-5.2
      months). The postoperative visual acuity improved in all eyes and ranged from
      20/100 to 20/30 (mean, 20/50). At the final visit, OCT examination revealed well
      preserved foveal structure in all eyes. Mild nuclear sclerosis developed in one
      eye. CONCLUSIONS: Pars plana vitrectomy followed by ILM removal and injection of
      subretinal rtPA-assisted pneumatic displacement appears to be effective in both
      improving visual acuity and preserving the foveal structure in eyes with recent
      massive multilevel macular hemorrhage secondary to RAMA.

PMID- 22467587
TI  - Beauveria bassiana keratitis in bullous keratopathy: antifungal sensitivity
      testing and management.
AB  - PURPOSE: Beauveria bassiana is a ubiquitous fungus available as an insecticide.
      In humans, it has limited virulence; to our knowledge, only 3 cases of invasive
      disease and 10 cases of keratitis have been documented. METHODS AND RESULTS: We
      report the first case of B bassiana keratitis in a patient with aphakic bullous
      keratopathy. The fungal keratitis proved to be highly resistant to topical
      clotrimazole. Molecular identification was based on DNA sequence analysis. The
      minimal inhibitory concentrations (MIC) obtained were 2 ug/mL for voriconazole,
      0.250 ug/mL for posaconazole, and >128 ug/mL for fluconazole; amphotericin B MIC
      was >16 ug/mL. In the absence of clinical improvement, a penetrating keratoplasty
      (PK) was performed. The patient was discharged on topical and systemic
      voriconazole and prednisolone 40 mg PO/day. The eye remained calm with a
      transparent cornea and clear anterior chamber. CONCLUSIONS: B bassiana keratitis
      is extremely rare, with only a few cases reported. Its risk factors are unknown.
      We report the first case in a patient with aphakic bullous keratopathy, which
      proved highly resistant to antifungal therapy (antifungal susceptibility results
      are presented). A PK was necessary for clinical improvement. A review of the
      literature is performed in an effort to define therapeutic strategies.

PMID- 22467589
TI  - Visual function and quality of life in pseudophakic patients before and after
      capsulotomy.
AB  - PURPOSE: To assess the correlation between visual acuity, visual function, and
      health-related quality of life before and after neodymium:YAG laser posterior
      capsulotomy. METHODS: A total of 150 patients with posterior capsule
      opacification (PCO) were examined before and after capsulotomy. Ocular
      examination, visual acuity, patient reports of satisfaction with vision, and
      disease-specific (VF-14 Index of Visual Functions) and generic (EuroQol: EQ-5D)
      outcomes were measured at baseline and 3 weeks after treatment. RESULTS: After
      capsulotomy, patients showed significant improvements in binocular visual acuity,
      VF-14 index, satisfaction with vision, and EQ-5D measures. The average gains in
      visual function and quality of life were apparent in groups with good visual
      outcome and poor visual outcome. The VF-14 score improvement was moderately
      correlated with the EuroQol Visual Analogue Scale score improvement, showing
      stronger correlations with changes in self-reported satisfaction with vision than
      did gains in binocular visual acuity. CONCLUSIONS: Measuring of the outcomes of
      capsulotomy by clinical indicators alone may underestimate the overall benefits
      of treatment. Visual acuity in conjunction with visual function and health
      related quality of life questionnaires will likely prove to be better indicators
      of the need for and outcome of capsulotomy.

PMID- 22467590
TI  - Fourier domain OCT measurement of macular, macular ganglion cell complex, and
      peripapillary RNFL thickness in glaucomatous Chinese eyes.
AB  - PURPOSE: To evaluate and compare the glaucoma discrimination ability of macula,
      macular ganglion cell complex (mGCC), and peripapillary nerve fiber layer (ppNFL)
      thickness in Chinese patients using Fourier-domain optical coherence tomography
      (FD-OCT). METHODS: A total of 64 normal subjects (N), 47 glaucoma suspects (GS),
      and 48 glaucoma patients (G) were enrolled in the study. The thickness of mGCC,
      ppNFL, and total macula were measured using RTVue-100 FD-OCT (software version:
      4.0.7.5; Optovue). The GCC and ONH protocols were used for obtaining images in
      all subjects. For each binocular subject, one eye was chosen randomly for
      analysis. RESULTS: The average thicknesses of macular, mGCC, and ppNFL in normal
      eyes were significantly different from those in GS or G eyes (p<0.001). The mGCC
      thickness correlated well with ppNFL thickness (correlation coefficients for N,
      GS, and G eyes are 0.397 [p=0.001], 0.822 [p<0.0001], and 0.865 [p<0.0001]).
      Areas under receiver operating characteristic curve of macular, mGCC, and ppNFL
      thickness are 0.940 (p<0.0001), 0.998 (p<0.0001), and 0.977 (p<0.0001),
      discriminating G from N eyes. There was no significant difference comparing the
      discriminating powers of NFL, GCC, and macular thickness. CONCLUSIONS: The mGCC
      measurements provide another measurement of neural loss in glaucoma, and may
      serve as a promising parameter for ppNFL thickness in the clinical assessment of
      glaucoma. For glaucomatous eyes, mGCC and ppNFL thicknesses performed better
      discriminating abilities compared with macular thickness.

PMID- 22467591
TI  - Combination therapy with focal laser photocoagulation and intravitreal
      ranibizumab for polypoidal choroidal vasculopathy: a case series.
AB  - PURPOSE: The study aim is to describe the clinical outcomes of patients with
      polypoidal choroidal vasculopathy (PCV) treated with focal argon laser
      photocoagulation and ranibizumab combination therapy. METHODS: This study is a
      retrospective case series of 6 patients (6 eyes) diagnosed with PCV who received
      combination therapy with argon laser photocoagulation and ranibizumab and have at
      least 12 months follow-up. Argon laser photocoagulation was applied directly to
      the polypoidal lesions as identified on indocyanine green angiography and
      followed by a course of intravitreal ranibizumab injections. The primary outcome
      measures were the mean change in logMAR visual acuity and the mean change in
      central macular thickness (CMT) at final follow-up. RESULTS: The mean (SD)
      duration of follow-up was 1.09 (0.22) years. At the final follow-up the
      difference (95% confidence interval [CI]) in logMAR acuity was 0.48 (0.10-0.74)
      (p=0.01) and the difference (95% CI) in CMT was 207 um (35-490) (p=0.02) on
      optical coherence tomography. The mean (SD) number of ranibizumab injections per
      eye was 4.83 (3.6). The mean (SD) number of laser treatments per eye was 1.16
      (0.4). CONCLUSIONS: In this study, combination therapy with focal argon laser
      photocoagulation and intravitreal ranibizumab resulted in improved visual acuity
      and clinical outcomes for patients with PCV for up to 1 year.

PMID- 22467592
TI  - Prisms are effective in resolving diplopia from incomitant, large, and combined
      strabismus.
AB  - PURPOSE: To assess the effectiveness of prisms in the management of diplopia in
      patients with incomitant, large, and combined strabismus. MATERIALS AND METHODS:
      Data were collected retrospectively from the medical records of 64 patients who
      were prescribed prisms for symptomatic diplopia due to restrictive strabismus.
      The main outcome measure was resolution of diplopia (diplopia score 1 or 2). Data
      on the number of patients who continued wearing prisms versus those who opted for
      surgery were derived based on follow-up records. RESULTS: Among 64 patients, 72%
      of patients reported complete or partial resolution of diplopia after prism use.
      In patients who were prescribed =10 PD (n=18) and those with oblique prisms
      (n=18), 67% and 50%, respectively, reported resolution of diplopia. More patients
      with vertical prism reported improvement in double vision symptoms (83%) than
      those who were prescribed horizontal prism (70%, p=0.04). During follow-up, 73%
      of the cohort continued using prisms while 23% of patients opted for strabismus
      surgery. CONCLUSIONS: Prisms are an effective modality and should be considered
      in the initial or interim management of patients with diplopia from complex
      ocular misalignments.

PMID- 22467593
TI  - Short-term use of inhaled and intranasal corticosteroids is not associated with
      glaucoma progression on optical coherence tomography.
AB  - PURPOSE: To compare the changes in retinal nerve fiber layer (RNFL) thickness and
      optic nerve cup/disc ratio on optical coherence tomography (OCT) between users
      and nonusers of inhaled and intranasal corticosteroids (ICS). METHODS:
      Retrospective study of participants with glaucoma or glaucoma suspect having 2 or
      more OCTs during a 6-year period. The rates of change in Stratus OCT fast RNFL
      thickness scan and fast optic disc scan data were compared between ICS users and
      nonuser controls using random coefficient models. RESULTS: A total of 170
      participants met the inclusion criteria, of whom 42 (25%) were ICS users and 128
      (75%) were controls. The mean duration of follow-up was 3.2 years. There were no
      significant differences in the mean rates of change in superior RNFL (-0.8874
      um/y ICS users; -0.8592 um/y controls; p=0.943), nasal RNFL (-0.0529 um/y ICS
      users; -0.3577 um/y controls; p=0.419), inferior RNFL (0.2703 um/y ICS users; 
      0.1910 um/y controls; p=0.165), and temporal RNFL (-0.3618 um/y ICS users; 
      0.3612 um/y controls; p=0.998) between ICS users and controls. There were no
      significant differences in the mean rates of change in horizontal cup/disc ratio
      (-0.0047 um/y ICS users; 0.0002 um/y controls; p=0.212) and vertical cup/disc
      ratio (0.0013 um/y ICS users; 0.0029 um/y; p=0.717) between ICS users and
      controls. CONCLUSIONS: We found no significant difference in the rates of RNFL or
      optic nerve cup/disc ratio progression among individuals with glaucoma or
      glaucoma suspect following short-term ICS use.

PMID- 22467594
TI  - Impact of the donor body mass index on the survival of pediatric liver transplant
      recipients and post-transplant obesity.
AB  - In adult liver transplant recipients, the donor body mass index (dBMI) is
      associated with posttransplant obesity but not with graft or patient survival.
      Because of the obesity epidemic in the United States and the already limited
      supply of liver donors, clarifying whether the dBMI affects pediatric outcomes is
      important. United Network for Organ Sharing data for pediatric liver transplants
      in the United States (1990-2010) were evaluated. Data on transplants performed
      between 2004 and 2010 (n = 3788) were used for survival analyses with Kaplan
      Meier and Cox proportional hazards models and for posttransplant obesity analyses
      with generalized estimating equations. For children receiving adult donor livers,
      a dBMI of 25 to <35 kg/m(2) was not associated with graft or patient survival in
      univariate or multivariate analyses. A dBMI >= 35 kg/m(2) increased the risk of
      graft loss [hazard ratio (HR) = 2.54, 95% confidence interval (CI) = 1.29-5.01, P
      = 0.007] and death (HR = 3.56, 95% CI = 1.64-7.72, P = 0.001). For pediatric
      donors, the dBMI was not associated with graft loss or mortality in a univariate
      or multivariate analysis. An overweight or obese donor was not a risk factor for
      posttransplant obesity. Overweight and obesity are common among liver transplant
      donors. This analysis suggests that for adult donors, a body mass index (BMI) of
      25 to <35 kg/m(2) should not by itself be a contraindication to liver donation.
      Severe obesity (BMI >= 35 kg/m(2)) in adult donors increased the risk of graft
      loss and mortality, even after adjustments for recipient, donor, and transplant
      risk factors. Posttransplant obesity was not associated with the dBMI in this
      analysis. Further research is needed to clarify the impact of donor obesity on
      pediatric liver transplant recipients.

PMID- 22467595
TI  - Types of imaging, Part 1: Electron microscopy.

PMID- 22467596
TI  - Flow cytometry assessment of residual melanoma cells in tumor-infiltrating
      lymphocyte cultures.
AB  - Adoptive transfer of tumor-infiltrating lymphocytes (TIL) is in development for
      the treatment of metastatic melanoma. In phase II clinical trials, patients with
      metastatic melanoma that received TIL after preconditioning had a 50-70% clinical
      response rate. The current approach to generate TIL is to culture melanoma enzyme
      digests in the presence of IL-2 for a 10- to 20-day period followed by 2 weeks of
      rapid expansion (REP). Prior to administration, cell therapies are characterized
      and tested for purity. TIL are characterized by CD3 surface marker expression,
      and purity is assessed by the amount of tumor remaining in culture. Evaluating
      TIL purity has traditionally been done by immunohistochemistry, which is often
      considered semiquantitative. To generate a quantitative assay, we used
      multiparameter flow cytometry to evaluate the presence of viable tumor cells by
      staining TIL populations with a viability dye and an antibody cocktail that
      detects intracellular tumor-antigens gp100, Mart-1, tyrosinase, S100, and surface
      tumor-antigen melanoma chondroitin sulfate proteoglycan (MCSP), and CD3 on T
      cells. Tumors were identified by gating on the viable CD3(-) population. Antigens
      in tumors were initially optimized with individual antibodies using both
      immunohistochemistry and flow cytometry. When eight different tumor cell lines
      were spiked into an activated T cell culture, flow cytometry was able to
      distinguish lymphocytes from tumors in all samples tested. Most importantly, the
      assay was able to detect melanoma cells in all enzyme digests (9/9) from patient
      samples. After IL-2-induced TIL expansion, there was a significant decrease in
      tumor cells; tumor cells were detected in only 2 of 12 samples. In eight IL-2
      induced TIL samples that were further expanded in REP, no tumor cells were
      detected. We have demonstrated that flow cytometry is an alternative to
      immunohistochemistry for defining the purity of a TIL population.

PMID- 22467597
TI  - Sirenomelia apus after trimethoprim exposure: first-trimester ultrasound
      diagnosis-a case report.
AB  - We report the early prenatal ultrasound diagnosis of sirenomelia apus at 12+4
      weeks in a patient with trimethoprim exposure in the vulnerable period. First
      trimester scan revealed a malformed fetus with one femur, one small tibia, no
      feet, intraabdominal unilocular cystic structure, and two-vessel umbilical cord
      with allantoic cyst. Ultrasound visualization with two/three/four-dimensions was
      helpful in the process of parental counseling.

PMID- 22467598
TI  - Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a
      single association with inflammatory bowel diseases.
AB  - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are common forms of
      inflammatory bowel disease (IBD). Monozygotic (MZ) twin discordance rates and
      epidemiologic data implicate that environmental changes and epigenetic factors
      may play a pathogenic role in IBD. DNA methylation (the methylation of cytosines
      within CpG dinucleotides) is an epigenetic modification, which can respond to
      environmental influences. We investigated whether DNA methylation might be
      connected with IBD in peripheral blood leukocyte (PBL) DNA by utilizing genome
      wide microarrays. METHODS: Two different high-throughput microarray-based methods
      for genome-wide DNA methylation analysis were employed. First, DNA isolated from
      MZ twin pairs concordant (CD: 4; UC: 3) and discordant (CD: 4; UC: 7) for IBD was
      interrogated by a custom-made methylation-specific amplification microarray
      (MSAM). Second, the recently developed Illumina Infinium HumanMethylation450
      BeadChip arrays were used on 48 samples of PBL DNA from discordant MZ twin pairs
      (CD: 3; UC: 3) and treatment-naive pediatric cases of IBD (CD: 14; UC: 8), as
      well as controls (n = 14). The microarrays were validated with bisulfite
      pyrosequencing. RESULTS: The MSAMs did not yield significant IBD associations.
      The Methylation BeadChip approach identified a single DNA methylation association
      of IBD at TEPP (testis, prostate and placenta-expressed protein) when DNA
      isolated selectively from peripheral blood mononuclear cells was analyzed (8.6%
      increase in methylation between CD and control, FDR = 0.0065). CONCLUSIONS:
      Microarray interrogation of IBD-dependent DNA methylation from PBLs appears to
      have limited ability to detect significant disease associations. More detailed
      and/or selective approaches may be useful for the elucidation of connections
      between the DNA methylome and IBD in the future.

PMID- 22467599
TI  - Encapsulation of hemoglobin inside liposomes surface conjugated with
      poly(ethylene glycol) attenuates their reactions with gaseous ligands and
      regulates nitric oxide dependent vasodilation.
AB  - Acellular hemoglobin (Hb)-based O2 carriers (HBOCs) are being investigated as red
      blood cell (RBC) substitutes for use in transfusion medicine. However, commercial
      acellular HBOCs elicit both vasoconstriction and systemic hypertension which
      hampers their clinical use. In this study, it is hypothesized that encapsulation
      of Hb inside the aqueous core of liposomes should regulate the rates of NO
      dioxygenation and O2 release, which should in turn regulate its vasoactivity. To
      test this hypothesis, poly(ethylene glycol) (PEG) conjugated liposome
      encapsulated Hb (PEG-LEHs) dispersions were prepared using human and bovine Hb.
      In this study, the rate constants for O2 dissociation, CO association, and NO
      dioxygenation were measured for free Hb and PEG-LEH dispersions using stopped
      flow UV-visible spectroscopy, while vasoactivity was assessed in rat aortic ring
      strips using both endogenous and exogenous sources of NO. It was observed that
      PEG-LEH dispersions had lower O2 release and NO dioxygenation rate constants
      compared with acellular Hbs. However, no difference was observed in the CO
      association rate constants between free Hb and PEG-LEH dispersions. Furthermore,
      it was observed that Hb encapsulation inside vesicles prevented Hb dependent
      inhibition of NO-mediated vasodilation. In addition, the magnitude of the
      vasoconstrictive effects of Hb and PEG-LEH dispersions correlated with their
      respective rates of NO dioxygenation and O2 release. Overall, this study
      emphasizes the pivotal role Hb encapsulation plays in regulating gaseous ligand
      binding/release kinetics and the vasoactivity of Hb.

PMID- 22467600
TI  - Disentangling diffusion information of individual components in a mixture with a
      3D COMPACT-IDOSY NMR experiment.
AB  - A new 3D diffusion-ordered heteronuclear NMR experiment COMPACT-IDOSY (cross
      polarization optimized multisite polarized accelerated time internally encoded
      diffusion ordered spectroscopy) has been designed and experimentally implemented
      on a mixture of flavonoids rutin and quercetin. The pulse sequence uses a cross
      polarization mixing period and diffusion encoding gradients internally
      incorporated into the coherence transfer interval of a long-range heteronuclear
      correlation experiment. Substantial reduction in experimental time, good
      sensitivity and excellent resolution of signal overlap lead to the accurate
      determination of translational diffusion coefficients of individual components in
      the mixture.

PMID- 22467601
TI  - Is there an en route folding intermediate for Cold shock proteins?
AB  - Cold shock proteins (Csps) play an important role in cold shock response of a
      diverse number of organisms ranging from bacteria to humans. Numerous studies of
      the Csp from various species showed that a two-state folding mechanism is
      conserved and the transition state (TS) appears to be very compact. However, the
      atomic details of the folding mechanism of Csp remain unclear. This study
      presents the folding mechanism of Csp in atomic detail using an all-atom Go model
      based simulations. Our simulations predict that there may exist an en route
      intermediate, in which beta strands 1-2-3 are well ordered and the contacts
      between beta1 and beta4 are almost developed. Such an intermediate might be too
      unstable to be detected in the previous fluorescence energy transfer experiments.
      The transition state ensemble has been determined from the P(fold) analysis and
      the TS appears even more compact than the intermediate state.

PMID- 22467602
TI  - Long-term outcomes of stereotactic body radiation therapy in the treatment of
      hepatocellular cancer as a bridge to transplantation.
AB  - Hepatocellular carcinoma (HCC) is potentially curable with hepatic resection or
      transplantation. Few patients are eligible for resection, and many face a long
      wait for donor organ availability for liver transplantation. Here we report the
      safety and efficacy of stereotactic body radiation therapy (SBRT), the explant
      pathology findings and survival of patients treated with SBRT as a bridge to
      transplantation for HCC. From April 2005 to August 2010, 10 patients with 11 HCCs
      were treated with SBRT as a bridge to transplantation. All patients were
      evaluated by a liver transplant surgeon before radiosurgery. SBRT was delivered
      with the CyberKnife robotic radiosurgery system. After SBRT, all patients
      underwent orthotopic liver transplantation. The tumor response was determined by
      explant pathology. The median follow-up was 62 months from the time of SBRT. The
      mean time on the liver transplant wait list was 163 days. The median tumor size
      was 3.4 cm (range = 2.5-5.5 cm). The median SBRT dose was 51 Gy (range = 33-54
      Gy) in 3 fractions. The median time from SBRT to liver transplantation was 113
      days (range = 8-794 days). At 5 years, the overall survival rate and the disease
      free survival rate were both 100%. Overall, 4 of the 10 patients (40%)
      experienced acute toxicity. Most toxicities were grade 1, and they included
      nausea, fatigue, and abdominal discomfort. One patient had grade 2
      nausea/vomiting. Explant pathology revealed no viable tumor in 3 of the 11 tumors
      for a complete response rate of 27%. The remaining 8 tumors decreased or remained
      stable in size. In conclusion, with a median follow-up over 5 years, we have
      found that SBRT as a bridge to liver transplantation for HCC is feasible and well
      tolerated. SBRT for HCC may enable patients to remain on the list for frequently
      curative transplantation during the wait for organ availability.

PMID- 22467603
TI  - Thalamic connections of auditory cortex in marmoset monkeys: lateral belt and
      parabelt regions.
AB  - The primate auditory cortex is comprised of a core region of three primary areas,
      surrounded by a belt region of secondary areas and a parabelt region lateral to
      the belt. The main sources of thalamocortical inputs to the auditory cortex are
      the medial geniculate complex (MGC), medial pulvinar (PM), and several adjoining
      nuclei in the posterior thalamus. The distribution of inputs varies
      topographically by cortical area and thalamic nucleus, but in a manner that has
      not been fully characterized in primates. In this study, the thalamocortical
      connections of the lateral belt and parabelt were determined by placing
      retrograde tracer injections into various areas of these regions in the marmoset
      monkey. Both regions received projections from the medial (MGm) and posterodorsal
      (MGpd) divisions of the medial geniculate complex (MGC); however, labeled cells
      in the anterodorsal (MGad) division were present only from injections into the
      caudal belt. Thalamic inputs to the lateral belt appeared to come mainly from the
      MGC, whereas the parabelt also received a strong projection from the PM,
      consistent with its position as a later stage of auditory cortical processing.
      The results of this study also indicate that the organization of the marmoset
      auditory cortex is similar to other primates.

PMID- 22467604
TI  - Standardizing minimal residual disease by flow cytometry for precursor B lineage
      acute lymphoblastic leukemia in a developing country.
AB  - BACKGROUND: In addition to standard risk criteria at diagnosis, minimal residual
      disease (MRD) following initiation of therapy is a well-recognized risk factor to
      predict relapse. Literature from developing countries addressing therapeutic or
      laboratory practices related to MRD, is largely lacking. In a first paper from
      India, we describe our experience in establishing a flow cytometry-based MRD
      assay for precursor B lineage ALL (BCP-ALL) with emphasis on the assay
      standardization and cost. METHODS: Normal templates for B cell development were
      established in 10 control patients using CD45, CD11a, CD38, CD20, CD10, CD19,
      CD58, CD34, CD123, and CD22. BCP-ALL samples (n = 42) were characterized at
      diagnosis to identify a suitable marker for follow-up during mid (D+21) and end
      of induction (D+33). Both, multiparametric immunophenotyping and single marker
      detection of LAIP were used for data analysis. RESULTS: In 95.2% of BCP-ALL at
      least two informative markers could be obtained when a minimum of four cocktail
      combinations were used. The combination CD20, CD10, CD45, and CD19 was the most
      useful (71.4%) followed by combinations containing CD38 (66.7%), CD22 (57.1%),
      CD11a (52.4%), and CD58 (33.3%). Using our approach, 60 and 47% of patients had
      detectable MRD at mid and end induction time points, respectively. CONCLUSION: We
      have described a relatively cost effective MRD panel which is applicable to over
      90% of patients. We hope that this data would encourage more centers in India and
      other resource constrained health delivery systems to develop MRD assays.

PMID- 22467605
TI  - High-throughput methods for miniaturization and automation of monoclonal antibody
      purification processes.
AB  - In the last decade, high-throughput downstream process development techniques
      have entered the biopharmaceutical industry. As chromatography is the standard
      downstream purification method, several high-throughput chromatographic methods
      have been developed and applied including miniaturized chromatographic columns
      for utilization on liquid handling stations. These columns were used to setup a
      complete downstream process on a liquid handling station for the first time. In
      this article, a monoclonal antibody process was established in lab-scale and
      miniaturized afterwards. The scale-down methodology is presented and discussed.
      Liquid handling in miniaturized single and multicolumn processes was improved and
      applicability was demonstrated by volume balances. The challenges of absorption
      measurement are discussed and strategies were shown to improve volume balances
      and mass balances in 96-well microtiter plates. The feasibility of miniaturizing
      a complete downstream process was shown. In the future, analytical bottlenecks
      should be addressed to gain the full benefit from miniaturized complete process
      development.

PMID- 22467607
TI  - Recognize the tipping points in vital signs: beware the treacherous triads.

PMID- 22467608
TI  - Capping a cuffed tracheostomy tube.

PMID- 22467610
TI  - Fluid management strategies in heart failure.
AB  - In patients with chronic heart failure, fluid retention (or hypervolemia) is
      often the stimulus for acute decompensated heart failure that requires
      hospitalization. The pathophysiology of fluid retention is complex and involves
      both hemodynamic and clinical congestion. Signs and symptoms of both hemodynamic
      and clinical congestion should be assessed serially during hospitalization. Core
      heart failure drug and cardiac device therapies should be provided, and
      ultrafiltration may be warranted. Critical care, intermediate care, and telemetry
      nurses have roles in both assessment and management of patients hospitalized with
      acute decompensated heart failure and fluid retention. Nurse administrators and
      managers have heightened their attention to fluid retention because the Medicare
      performance measure known as the risk-standardized 30-day all-cause readmission
      rate after heart failure hospitalization can be attenuated by fluid management
      strategies initiated by nurses during a patient's hospitalization.

PMID- 22467611
TI  - Critical care nurses' role in implementing the "ABCDE bundle" into practice.
AB  - Imagine working in an environment where all patients undergoing mechanical
      ventilation are alert, calm, and delirium free. Envision practicing in an
      environment where nonvocal patients can effectively express their need for better
      pain control, repositioning, or emotional reassurance. Picture an intensive care
      unit where a nurse-led, interprofessional team practices evidence-based, patient
      centered care focused on preserving and/or restoring their clients' physical,
      functional, and neurocognitive abilities. A recently proposed bundle of practices
      for the intensive care unit could advance the current practice environment toward
      this idealized environment. The Awakening and Breathing Coordination, Delirium
      Monitoring and Management, and Early Mobility (ABCDE) bundle incorporates the
      best available evidence related to delirium, immobility, sedation/analgesia, and
      ventilator management in the intensive care unit for adoption into everyday
      clinical practice.

PMID- 22467612
TI  - The journey to zero central catheter-associated bloodstream infections: culture
      change in an intensive care unit.
AB  - A process change with the goal of decreasing and ultimately eliminating
      bloodstream infections associated with central catheters in critical care
      patients was implemented at Riverside Methodist Hospital. This process of
      implementation resulted in a culture change in the hospital's medical surgical
      intensive care unit. Keys to success included a multidisciplinary team approach,
      support from persons with a stake in the process, and provision of continuous
      feedback. The lessons learned in this journey at Riverside Methodist Hospital can
      help caregivers at other hospitals decrease the occurrence of these life
      threatening infections.

PMID- 22467613
TI  - So you want to change practice: recognizing practice issues and channeling those
      ideas.
AB  - Applying the best evidence to support nursing practice and generating new
      knowledge for use in practice are the hallmarks of excellence and allow
      practitioners to meet patient care quality and safety priorities. Although
      identifying a patient care problem comes easily to staff nurses, the process of
      clarifying the problem and channeling those ideas through to a practice change
      can be daunting for bedside nurses. This article provides guidance to staff
      nurses who want to identify a clinical problem and change practice.

PMID- 22467614
TI  - Developing ethical skills: from sensitivity to action.
AB  - Acute and critical care nurses routinely encounter ethical "quandaries" such as
      providing perceived futile care. Other everyday ethically important occurrences
      may go unrecognized, however, thus diminishing their importance to moral nursing
      practice. This column presents a framework that may assist in developing specific
      skills to recognize and engage in both critical and everyday ethical situations
      with confidence. James Rest's Four Component Model addresses the role of the
      moral practitioner from initial recognition that an ethical situation exists to
      implementation of a justifiable action. Patient/provider scenarios are used to
      illustrate components of Rest's model followed by an approach to distinguish
      ethical from nonethical situations. Practical strategies to enhance ethical
      skills such as development of nursing ethics groups and providing continuing
      ethics education also are presented.

PMID- 22467615
TI  - Defibrillation of obese patients.

PMID- 22467616
TI  - Catheter-associated urinary tract infections.

PMID- 22467618
TI  - I am a critical care nurse.

PMID- 22467619
TI  - Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of
      antidiuretic hormone, and cerebral salt-wasting syndrome in traumatic brain
      injury.
AB  - Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of
      antidiuretic hormone, and cerebral salt-wasting syndrome are secondary events
      that affect patients with traumatic brain injury. All 3 syndromes affect both
      sodium and water balance; however, they have differences in pathophysiology,
      diagnosis, and treatment. Differentiating between hypernatremia (central
      neurogenic diabetes insipidus) and the 2 hyponatremia syndromes (syndrome of
      inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting
      syndrome) is critical for preventing worsening neurological outcomes in patients
      with head injuries.

PMID- 22467620
TI  - Sleep and immune function.
AB  - Scientists are only beginning to fully understand the purpose of sleep and its
      underlying mechanisms. Lack of sleep is associated with many diseases, including
      infection, and with increased mortality. Lack of proper sleep is an important
      problem in the intensive care unit, and interventions have been designed to
      improve it. Sleep is associated with immune function, and this relationship is
      partially based on the physiological basis of sleep, sleep architecture, the
      sleep-wake cycle, cytokines and the hypothalamic-pituitary axis.

PMID- 22467622
TI  - Surveillance: A strategy for improving patient safety in acute and critical care
      units.
AB  - Surveillance is a nursing intervention that has been identified as an important
      strategy in preventing and identifying medical errors and adverse events. The
      definition of surveillance proposed by the Nursing Intervention Classification is
      the purposeful and ongoing acquisition, interpretation, and synthesis of patient
      data for clinical decision making. The term surveillance is often used
      interchangeably with the term monitoring, yet surveillance differs significantly
      from monitoring both in purpose and scope. Monitoring is a key activity in the
      surveillance process, but monitoring alone is insufficient for conducting
      effective surveillance. Much of the attention in the bedside patient safety
      movement has been focused on efforts to implement processes that ultimately
      improve the surveillance process. These include checklists, interdisciplinary
      rounds, clinical information systems, and clinical decision support systems. To
      identify optimal surveillance patterns and to develop and test technologies that
      assist critical care nurses in performing effective surveillance, more research
      is needed, particularly with innovative approaches to describe and evaluate the
      best surveillance practices of bedside nurses.

PMID- 22467624
TI  - Modeling the human mandible under masticatory loads: which input variables are
      important?
AB  - Finite element analyses (FEA) that have simulated masticatory loadings of the
      human mandible differ significantly with regard to their basic input variables
      such as material properties, constraints, and applied forces. With sensitivity
      analyses it is possible to assess how the choice of different input values and
      the degree of model simplification affect FEA results. However, published FEA
      studies are rarely accompanied by sensitivity analyses so that the robusticity of
      their results is impossible to assess. Here, we conduct a sensitivity analysis
      with an FE model of a human mandible to quantify the relative importance of
      several modeling decisions: (1) the material properties assigned to the
      cancellous bone tissue; (2) the inclusion or not of the periodontal ligament; (3)
      the constraints at the joints and bite point; and (4) the orientation of applied
      muscle forces. We study the effects of varying these properties by analysing the
      strain magnitudes and directions across the model surface. In addition, we
      perform a geometric morphometric analysis of the deformation resulting from the
      loading of each model. The results show that the effects of altering the
      different model properties can be significant and that most effects are
      potentially large enough to cause problems for the biological interpretation of
      FEA results. We therefore recommend that researchers conduct more sensitivity
      analyses than at present to assess the robusticity of their FEA results and their
      biological conclusions.

PMID- 22467623
TI  - Recipient survival and graft survival are not diminished by simultaneous liver
      kidney transplantation: an analysis of the united network for organ sharing
      database.
AB  - Recipients of solitary liver and kidney transplants are living longer, and this
      increases their risk of long-term complications such as recurrent hepatitis C
      virus (HCV) and drug-induced nephrotoxicity. These complications may require
      retransplantation. Since the adoption of the Model for End-Stage Liver Disease,
      the number of simultaneous liver-kidney transplantation (SLK) procedures has
      increased. However, there are no standardized criteria for organ allocation to
      SLK candidates. The aims of this study were to retrospectively compare recipient
      and graft survival with liver transplantation alone (LTA), SLK, kidney after
      liver transplantation (KALT), and liver after kidney transplantation (LAKT) and
      to identify independent risk factors affecting recipient and graft survival. The
      United Network for Organ Sharing/Organ Procurement and Transplantation Network
      database (1988-2007) was queried for adult LTA (66,026), SLK (2327), KALT (1738),
      and LAKT procedures (242). After adjustments for potential confounding
      demographic and clinical variables, there was no difference in recipient
      mortality rates with LTA and SLK (P = 0.02). However, there was a 15% decreased
      risk of graft loss with SLK versus LTA (hazard ratio = 0.85, P < 0.001). The
      recipient and graft survival rates with SLK were higher than the rates with both
      KALT (P <0.001 and P <0.001) and LAKT (P = 0.003 and P < 0.001). The following
      were all identified as independent negative predictors of recipient mortality and
      graft loss: recipient age >= 65 years, male sex, black race, HCV/diabetes
      mellitus status, donor age >= 60 years, serum creatinine level >=2.0 mg/dL, cold
      ischemia time > 12 hours, and warm ischemia time > 60 minutes. Although the
      recent increase in the number of SLK procedures performed each year has
      effectively decreased the number of potential donor kidneys available to patients
      with end-stage renal disease (ESRD) awaiting kidney transplantation, SLK in
      patients with end-stage liver disease and ESRD is justified because of the lower
      risk of graft loss with SLK versus LTA as well as the superior recipient and
      graft survival with SLK versus serial liver-kidney transplantation.

PMID- 22467625
TI  - Unchanged distribution density of anionic sites on the glomerular wall in rats
      with streptozotocin-induced diabetic nephropathy.
AB  - As a cause of proteinuria in diabetic nephropathy, a decrease in anionic charge
      on the glomerular basement membrane (GBM) is considered to be related to protein
      leakage. However, the constancy of the anionic charge has been reported in
      several types of nephropathy. To elucidate the relation between glomerular
      protein leakage and anionic charge, we examined the distribution of anionic sites
      on the GBM and podocytes in diabetic rats induced by a single intravenous
      injection of 60 mg/kg of streptozotocin (STZ). Five months after the treatment
      with STZ, urinalysis for glucose and protein levels was conducted, and the
      kidneys were examined using electron microscopic cytochemistry for the assessment
      of anionic charge with two cationic probes. The distributions of anionic sites on
      the GBM demonstrated by two kinds of cationic markers in the diabetic rats were
      similar in density to those seen in the control animals. The distributions of
      anionic sites on the foot processes and cell membrane of podocytes were regular
      and also similar in density to that of the control group. From these results, we
      consider that the charge barrier of the GBM and podocytes is irrelevant to the
      protein leakage in diabetic rats.

PMID- 22467626
TI  - An atypical case of islet cell hyperplasia in a Wistar rat.
AB  - The present article describes an unusual proliferative islet finding observed
      incidentally in a young male Wistar rat in a 2-week toxicity study.
      Histologically, the islet lesion was characterized by diffuse enlargement of the
      islets, which consisted of peripheral proliferation of non-insulin-containing
      islet cells surrounding normal-appearing insulin-containing cells in the center.
      To the authors' knowledge, this is the first report of spontaneous proliferative
      islet lesion composed of non-insulin-containing cells in young rats.

PMID- 22467627
TI  - Structuration and integration of magnetic nanoparticles on surfaces and devices.
AB  - Different experimental approaches used for structuration of magnetic
      nanoparticles on surfaces are reviewed. Nanoparticles tend to organize on
      surfaces through self-assembly mechanisms controlled by non-covalent interactions
      which are modulated by their shape, size and morphology as well as by other
      external parameters such as the nature of the solvent or the capping layer.
      Further control on the structuration can be achieved by the use of external
      magnetic fields or other structuring techniques, mainly lithographic or atomic
      force microscopy (AFM)-based techniques. Moreover, results can be improved by
      chemical functionalization or the use of biological templates. Chemical
      functionalization of the nanoparticles and/or the surface ensures a proper
      stability as well as control of the formation of a (sub)monolayer. On the other
      hand, the use of biological templates facilitates the structuration of several
      families of nanoparticles, which otherwise may be difficult to form, simply by
      establishing the experimental conditions required for the structuration of the
      organic capsule. All these experimental efforts are directed ultimately to the
      integration of magnetic nanoparticles in sensors which constitute the future
      generation of hybrid magnetic devices.

PMID- 22467628
TI  - Microfluidic generation of acoustically active nanodroplets.
AB  - A microfluidic approach for the generation of perfluorocarbon nanodroplets as the
      primary emulsion with diameters as small as 300-400 nm is described. The system
      uses a pressure-controlled delivery of all reagents and increased viscosity in
      the continuous phase to drive the device into an advanced tip-streaming regime,
      which results in generation of droplets in the sub-micrometer range. Such
      nanodroplets may be appropriate for emerging biomedical applications.

PMID- 22467629
TI  - Estimation of raw material performance in mammalian cell culture using near
      infrared spectra combined with chemometrics approaches.
AB  - Understanding variability in raw materials and their impacts on product quality
      is of critical importance in the biopharmaceutical manufacturing processes. For
      this purpose, several spectroscopic techniques have been studied for raw material
      characterization, providing fast and nondestructive ways to measure quality of
      raw materials. However, investigations of correlation between spectra of raw
      materials and cell culture performance have been scarce due to their complexity
      and uncertainty. In this study, near-infrared spectra and bioassays of multiple
      soy hydrolysate lots manufactured by different vendors were analyzed using
      chemometrics approaches in order to address variability of raw materials as well
      as correlation between raw material properties and corresponding cell culture
      performance. Principal component analysis revealed that near-infrared spectra of
      different soy lots contain enough physicochemical information about soy
      hydrolysates to allow identification of lot-to-lot variability as well as vendor
      to-vendor differences. The identified compositional variability was further
      analyzed in order to estimate cell growth and protein production of two mammalian
      cell lines under the condition of varying soy dosages using partial least square
      regression combined with optimal variable selection. The performance of the
      resulting models demonstrates the potential of near-infrared spectroscopy as a
      robust lot selection tool for raw materials while providing a biological link
      between chemical composition of raw materials and cell culture performance.

PMID- 22467630
TI  - Assessment of the activity of ceftaroline against clinical isolates of penicillin
      intermediate and penicillin-resistant Streptococcus pneumoniae with elevated MICs
      of ceftaroline using an in vitro pharmacodynamic model.
AB  - OBJECTIVES: This study assessed the pharmacodynamics of ceftaroline against
      penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae with
      elevated MICs of ceftaroline using an in vitro pharmacodynamic model. METHODS:
      Nine isolates of S. pneumoniae, including one penicillin-susceptible isolate, one
      penicillin-intermediate isolate and seven penicillin-resistant isolates, were
      tested. The pharmacodynamic model was inoculated with a concentration of 1 *
      10(6) cfu/mL and ceftaroline was dosed twice daily (at 0 and 12 h) to simulate
      the fC(max) (maximum free concentration in serum) and t(1/2) (half-life in serum)
      obtained after 600 mg intravenous doses every 12 h (fC(max), 16 mg/L; t(1/2), 2.6
      h). Ceftaroline was compared with ceftriaxone dosed once daily to simulate the
      fC(max) and t(1/2) obtained after a 1 g dose (fC(max), 18 mg/L; t(1/2), 8.0 h).
      Samples were collected over 24 h to assess viable growth and possible changes in
      ceftaroline MICs over time. RESULTS: Ceftaroline fT(>MIC) (time of free serum
      concentration over the MIC) of 100% (ceftaroline MICs, <= 0.5 mg/L) was
      bactericidal (>= 3 log(10) killing) against all isolates at 6 h and completely
      eradicated all organisms at 12 and 24 h. No bacterial regrowth occurred over the
      study period and no changes in ceftaroline MICs were observed. Upon ceftriaxone
      exposure, S. pneumoniae isolates with ceftriaxone MICs of 0.12 and 0.25 mg/L were
      eradicated, but isolates with ceftriaxone MICs of 1-8 mg/L resulted in initial
      bacterial reduction at 6 h with organism regrowth at 12 h and no reduction in
      organism concentration, relative to the starting inoculum, at 24 h. CONCLUSIONS:
      Ceftaroline fT(>MIC) of 100% (ceftaroline MICs, <= 0.5 mg/L) was bactericidal (>=
      3 log(10) killing) and eradicated all S. pneumoniae at 12 and 24 h with no
      regrowth.

PMID- 22467631
TI  - Deleterious effect of ciprofloxacin on Rickettsia conorii-infected cells is
      linked to toxin-antitoxin module up-regulation.
AB  - OBJECTIVES: To confirm and better understand the deleterious effect of
      fluoroquinolones reported during Rickettsia conorii infection in humans. METHODS:
      We used a new plaque assay to test the effect of ciprofloxacin on cells infected
      by R. conorii. Controls were mock-treated infected cells and infected cells
      treated with doxycycline. We used real-time quantitative RT-PCR to quantify vapC
      and vapB transcripts in cells infected by R. conorii treated with ciprofloxacin
      or mock treated. RESULTS: By plaque assay, at baseline (0 h) there is no
      difference in lytic area between cells treated with ciprofloxacin (whatever
      concentration used) and controls. Ciprofloxacin at 0.5 and 50 mg/L induced a
      significant increase in lytic areas compared with the control at 2 h, 4 h, 6 h
      (P<0.0001) and 24 h (P<0.0001 and P=0.035, respectively) when not induced with
      doxycycline. By real-time quantitative RT-PCR, ciprofloxacin was found to cause
      an up-regulation of toxin-antitoxin (TA) module transcription. Indeed, the mRNA
      levels of vapC and vapB were significantly increased at 2 h and 4 h in cells
      treated with 50 mg/L ciprofloxacin (not with 0.5 mg/L ciprofloxacin) compared
      with control levels (fold change >2.9). CONCLUSIONS: These in vitro findings
      correlated with our previous clinical findings: fluoroquinolones have a
      deleterious effect during R. conorii infection, not found with doxycycline. We
      speculate that the toxic effect of fluoroquinolones on R. conorii-infected cells
      is mediated by the overexpression of TA, possibly followed by their release into
      the host cytoplasm as described in Rickettsia felis.

PMID- 22467632
TI  - Intravaginal ring delivery of tenofovir disoproxil fumarate for prevention of HIV
      and herpes simplex virus infection.
AB  - OBJECTIVES: A safe and effective topical prevention strategy will likely require
      sustained delivery of potent antiviral drugs and a delivery system that
      simultaneously maximizes drug distribution and overcomes the behavioural
      challenges related to adherence. Activity against HIV and herpes simplex virus
      (HSV) would be advantageous, given the epidemiological link between the two
      pathogens. We hypothesize that tenofovir disoproxil fumarate (tenofovir DF), a
      prodrug of tenofovir, may be more potent than tenofovir and ideal for sustained
      intravaginal ring (IVR) delivery. METHODS: The anti-HIV and anti-HSV activity of
      tenofovir and tenofovir DF were assessed in cell and explant models. Cumulative
      tenofovir DF release and stability from polyether urethane (PEU), ethylene-co
      vinyl acetate (EVA) and silicone IVRs were compared, and the activity and safety
      of drug released were evaluated in cervical explants and in a polarized dual
      chamber model. RESULTS: Tenofovir DF inhibited HIV and HSV at ~ 100-fold lower
      concentrations than tenofovir and retained activity in the presence of semen. PEU
      rings delivered >1 mg/day of tenofovir DF for 30 days. Pre-treatment of cervical
      explants with 10 MUg/mL tenofovir DF or eluants from PEU minirings resulted in
      >90% inhibition of HIV and reduced HSV-2 yields by 2.5 log. Tenofovir DF and
      eluants did not prevent cell growth or polarization, or have any deleterious
      effects on an epithelial barrier. CONCLUSIONS: The findings support the
      development of a PEU tenofovir DF ring, which may provide potent and sustained
      protection against HIV and HSV.

PMID- 22467634
TI  - The New York Times readers' opinions about paying people to take their medicine.
AB  - BACKGROUND: There has been considerable interest in using financial incentives to
      help people improve their health. However, paying people to improve their health
      touches on strongly held views about personal responsibility. METHOD: The New
      York Times printed two articles in June 2010 about patient financial incentives,
      which resulted in 394 comments from their online audience. The authors
      systematically analyzed those online responses to news media in order to
      understand the range of themes that were expressed regarding the use of financial
      incentives to improve health. RESULTS: The New York Times online readers revealed
      a broad range of attitudes about paying individuals to be healthy. Many comments
      reflected disdain for financial incentives, describing them as "absurd" or
      "silly." Other comments reflected the notion that financial incentives reward
      individuals for being irresponsible toward their health. Many individuals
      communicated concerns that paying individuals for healthy behaviors may weaken
      their internal drive to be healthy. A smaller set of comments conveyed support
      for financial incentives, recognizing it as a small sum to pay to prevent or
      offset higher costs related to chronic diseases. CONCLUSIONS: Although a
      measurable group of individuals supported financial incentives, most readers
      revealed negative perceptions of these approaches and an appeal for greater
      personal responsibility for individual health. Despite experimental success of
      financial incentives, negative perceptions may limit their public acceptability
      and uptake.

PMID- 22467635
TI  - The elasticity of time: associations between physical activity and use of time in
      adolescents.
AB  - The way an individual uses one's time can greatly affect his or her health. The
      purpose of this article was to examine the cross-sectional cross-elasticity
      relationships for use of time domains in a sample of Australian adolescents. This
      study analyzed 24-hour recall time use data collected using the Multimedia
      Activity Recall for Children and Adults (N = 2,200). Using simple linear
      regression, the authors calculated the difference in time devoted to a reference
      activity (i.e., screen time, sleep, or social) given 1 hour extra in the time
      devoted to a criterion activity (i.e., physical activity). The most elastic
      activities were screen time and school-related time. Every additional hour
      committed to physical activity was associated with 32 minutes less screen time.
      This relationship was more pronounced in obese adolescents (-56 minutes screen
      time) compared with normal (-31 minutes) and overweight (-27 minutes)
      adolescents. Promising behavior patterns exist, with screen time appearing as a
      highly elastic behavior.

PMID- 22467633
TI  - Prognosis of hospitalized patients with 2009 H1N1 influenza in Spain: influence
      of neuraminidase inhibitors.
AB  - BACKGROUND: The H1N1 influenza pandemic strain has been associated with a poor
      prognosis in hospitalized patients. The present report evaluates the factors
      influencing prognosis. METHODS: A total of 813 patients hospitalized with H1N1
      influenza in 36 hospitals (nationwide) in Spain were analysed. Detailed histories
      of variables preceding hospital admission were obtained by interview, validating
      data on medications and vaccine with their attending physicians. Data on
      treatment and complications during hospital stay were recorded. As definition of
      poor outcome, the endpoints of death and admission to intensive care were
      combined; and as a further outcome, length of stay was used. RESULTS: The mean
      age was 38.5 years (SD 22.8 years). There were 10 deaths and 79 admissions to
      intensive care (combined, 88). The use of neuraminidase inhibitors was reported
      by 495 patients (60.9%). The variables significantly associated with a poor
      outcome were diabetes (OR = 2.21, 95% CI = 1.21-4.02), corticosteroid therapy (OR
      = 3.37, 95% CI = 1.39-8.20) and use of histamine-2 receptor antagonists (OR =
      2.68, 95% CI = 1.14-6.36), while the use of neuraminidase inhibitors (OR = 0.57,
      95% CI = 0.34-0.94) was protective. Neuraminidase inhibitors within the first 2
      days after the influenza onset reduced hospital stay by a mean of 1.9 days (95%
      CI = 4.7-6.6). CONCLUSIONS: The use of neuraminidase inhibitors decreases the
      length of hospital stay and admission to intensive care and/or death.

PMID- 22467637
TI  - Systems thinking tools as applied to community-based participatory research: a
      case study.
AB  - Community-based participatory research (CBPR) is being used increasingly to
      address health disparities and complex health issues. The authors propose that
      CBPR can benefit from a systems science framework to represent the complex and
      dynamic characteristics of a community and identify intervention points and
      potential "tipping points." Systems science refers to a field of study that
      posits a holistic framework that is focused on component parts of a system in the
      context of relationships with each other and with other systems. Systems thinking
      tools can assist in intervention planning by allowing all CBPR stakeholders to
      visualize how community factors are interrelated and by potentially identifying
      the most salient intervention points. To demonstrate the potential utility of
      systems science tools in CBPR, the authors show the use of causal loop diagrams
      by a community coalition engaged in CBPR activities regarding youth drinking
      reduction and prevention.

PMID- 22467636
TI  - Dietary behaviors of a racially and ethnically diverse sample of overweight and
      obese Californians.
AB  - OBJECTIVES: To examine racial/ethnic differences in the dietary behaviors of
      overweight or obese adults using the 2007 California Health Interview Survey.
      METHOD: Data were obtained from the 2007 California Health Interview Survey, a
      population-based sample of noninstitutionalized adults in California. The sample
      included 26,721 adults aged 18 years and older whose body mass index status
      indicated that they were overweight or obese (body mass index >= 25), with 19,264
      non-Hispanic White; 1,749 African American/Black; 1,616 Asian/Pacific Islander;
      and 4,092 Latino respondents. Respondents were compared with regard to
      consumption of five categories of food: fruits, vegetables, French fries, soft
      drinks, and fast-food. Multivariable regression analyses were conducted to
      examine racial/ethnic differences in dietary behaviors, with and without
      adjustment for age, gender, nativity, marital status, education, income, and food
      insecurity. RESULTS: The findings suggested there were significant racial/ethnic
      differences in food preferences and that English proficiency, in part, explained
      some of these differences. Overweight/obese African American/Black respondents
      reported eating fruit (aBeta = -0.73, [95% confidence interval = -1.29, -0.17])
      and vegetables (aBeta = -0.71 [-1.18, -0.24]) fewer times per day and fast-food
      (aBeta = 0.21, [0.04, 0.38]) more times per day compared with their non-Hispanic
      White counterparts. Irrespective of language proficiency, Asian/Pacific Islanders
      reported eating significantly less fruit compared with non-Hispanic Whites.
      Limited English proficient (LEP) Asian/Pacific Islanders were found to eat
      vegetables (aBeta = 1.41, [0.47, 2.63]) more times per day than non-Hispanic
      Whites, in contrast to English proficient Asian/Pacific Islanders who were found
      to eat vegetables (aBeta = -0.64, [-1.11, -0.18]) fewer times per day compared
      with non-Hispanic Whites. Both LEP and English proficient Latinos ate vegetables
      less often and drank soft drinks and ate fast-food more often than non-Hispanic
      Whites. CONCLUSIONS: Efforts to intervene with individuals who are overweight or
      obese must include culturally and linguistically tailored interventions that
      consider how individuals' dietary behaviors are influenced by their racial/ethnic
      backgrounds.

PMID- 22467638
TI  - Stretchable semiconductor technologies with high areal coverages and strain
      limiting behavior: demonstration in high-efficiency dual-junction GaInP/GaAs
      photovoltaics.
AB  - Notched islands on a thin elastomeric substrate serve as a platform for dual
      junction GaInP/GaAs solar cells with microscale dimensions and ultrathin forms
      for stretchable photovoltaic modules. These designs allow for a high degree of
      stretchability and areal coverage, and they provide a natural form of strain
      limiting behavior, helping to avoid destructive effects of extreme deformations.

PMID- 22467639
TI  - A combinatorial approach for directing the amount of fibronectin fibrils
      assembled by cells that uses surfaces derivatized with mixtures of fibronectin
      and cell binding domains.
AB  - Fibrillar fibronectin (FN) has the crucial role of attracting and attaching cells
      as well as molecules that mediate tissue repair during wound healing. A previous
      study demonstrated higher extracellular staining of FN fibrils in cells cultured
      on surfaces tethered with an equimolar mixture of a FN binding domain and FN's
      cell binding domain, III1-2 and III9-10 respectively, than on surfaces with III9
      10 alone. The effect of varying surface amounts of III1-2 and III9-10 on the
      quantity of FN fibrils formed by NIH-3T3 fibroblasts was examined. GST tagged
      III1-2 and III9-10 were conjugated to polyurethane surfaces and ELISAs were used
      to identify the experimental design space or the range of concentrations of GST
      III1-2 and GST-III9-10 that demarcated the limits of protein loading on the
      surface. When GST-III1-2 was fixed and GST-III9-10 varied within the design
      space, the amount of FN fibrils measured by immunoblotting detergent insoluble
      cell lysates was dependent on the ratio of III9-10 to III1-2. When the total
      protein concentration was fixed and the mixture composition of GST-III1-2 and GST
      III9-10 varied such that it optimally covered the design space, a parabolic
      relationship between FN fibril amount and the ratio of III9-10 to III1-2 was
      obtained. This relationship had a maximum value when the surface was bonded to
      equal amounts of III1-2 and III9-10 (P<0.05). Thus the ratio of III9-10 to III1-2
      can be utilized to direct the quantity of FN fibrils formed on surfaces.

PMID- 22467640
TI  - Hyperoxia alters the mechanical properties of alveolar epithelial cells.
AB  - Patients with severe acute lung injury are frequently administered high
      concentrations of oxygen (>50%) during mechanical ventilation. Long-term exposure
      to high levels of oxygen can cause lung injury in the absence of mechanical
      ventilation, but the combination of the two accelerates and increases injury.
      Hyperoxia causes injury to cells through the generation of excessive reactive
      oxygen species. However, the precise mechanisms that lead to epithelial injury
      and the reasons for increased injury caused by mechanical ventilation are not
      well understood. We hypothesized that alveolar epithelial cells (AECs) may be
      more susceptible to injury caused by mechanical ventilation if hyperoxia alters
      the mechanical properties of the cells causing them to resist deformation. To
      test this hypothesis, we used atomic force microscopy in the indentation mode to
      measure the mechanical properties of cultured AECs. Exposure of AECs to hyperoxia
      for 24 to 48 h caused a significant increase in the elastic modulus (a measure of
      resistance to deformation) of both primary rat type II AECs and a cell line of
      mouse AECs (MLE-12). Hyperoxia also caused remodeling of both actin and
      microtubules. The increase in elastic modulus was blocked by treatment with
      cytochalasin D. Using finite element analysis, we showed that the increase in
      elastic modulus can lead to increased stress near the cell perimeter in the
      presence of stretch. We then demonstrated that cyclic stretch of hyperoxia
      treated cells caused significant cell detachment. Our results suggest that
      exposure to hyperoxia causes structural remodeling of AECs that leads to
      decreased cell deformability.

PMID- 22467642
TI  - Can projective drawings detect if a child experienced sexual or physical abuse? A
      systematic review of the controlled research.
AB  - Clinical observations have suggested that children who experience physical or
      sexual abuse may provide indicators in their drawings that can distinguish them
      from nonabused children. Some have even suggested that a child's drawings and the
      interpretive testimony of a trained mental health clinician should be admissible
      in court as evidence of a child's abuse status. Many of these comments, however,
      may reflect a limited consideration of the available research. The current
      article provides a comprehensive literature review of the controlled research to
      determine whether any graphic indicators (e.g., genitalia, omission of body
      parts) or predefined scoring system can reliability and validly discriminate
      abused from nonabused children. Results indicate that, although individual
      studies have found support for various indicators or scoring systems, these
      results are rarely replicated, many times studies finding significant results
      suffer from serious methodological flaws and alternative explanations for
      findings (e.g., mental illness) are often present. No graphic indicator or
      scoring system possessed sufficient empirical evidence to support its use for
      identifying sexual or physical abuse. A discussion of the legal ramifications of
      these results is provided.

PMID- 22467641
TI  - Interaction with CREB binding protein modulates the activities of Nrf2 and NF
      kappaB in cystic fibrosis airway epithelial cells.
AB  - Cystic fibrosis (CF) is characterized by inflammatory lung disease that
      significantly contributes to morbidity and mortality. Airway epithelial cells
      play a role in the inflammatory signaling in CF and have been reported to exhibit
      a number of dysfunctions in signaling cascades that modulate inflammation.
      Previously, we reported that the activity of nuclear factor erythroid-derived
      like 2 (Nrf2), a transcription factor that regulates antioxidant and
      cytoprotective protein expression, is diminished in CF epithelia (7). In this
      report, we examined the mechanism of Nrf2 dysregulation in vitro in human airway
      epithelial cell lines and primary cells and in vivo in nasal epithelia excised
      from DeltaF508 CF mutant mice. We found that cAMP-mediated signaling markedly
      reduces Nrf2 activity in CF vs. non-CF cells. Rp-cAMPS, a cAMP competitor,
      significantly corrected Nrf2 activity in CF cells, predominantly by increasing
      the nuclear accumulation of the transcription factor. Furthermore, we found that
      Rp-cAMPS significantly decreased NF-kappaB activation following inflammatory
      stimulation of CF cells. Further investigation revealed that Nrf2 and NF-kappaB
      compete for the transcriptional coactivator cAMP responsive element-binding
      protein (CREB) binding protein (CBP) and that Rp-cAMPS shifts CBP association in
      favor of Nrf2. Thus our findings provide a link between feedback to CF
      transmembrane regulator dysfunction and dysregulation of an inflammatory
      signaling pathway that modulates the coordinated activities of Nrf2 and NF
      kappaB. Furthermore, our studies suggest that strategies that shift CBP
      association away from NF-kappaB and toward Nrf2 could have potential therapeutic
      efficacy for reducing inflammation in patients with CF.

PMID- 22467643
TI  - Prevalence of traumatic brain injury in intimate partner violence offenders
      compared to the general population: a meta-analysis.
AB  - Intimate partner violence (IPV) is widespread. Several risk factors are
      associated with IPV perpetuation, including alcohol use and educational level.
      The aggression and violence associated with traumatic brain injury (TBI) suggest
      that brain trauma may also be a risk factor for IPV. To examine the association
      between TBI and IPV, the authors conducted a meta-analysis of peer-reviewed
      published studies reporting the prevalence of TBI in IPV perpetrators. The
      authors compared the frequency of TBI among IPV perpetuators to estimates of TBI
      in the general population using a single-sample test of proportions. Six studies
      containing a total of 222 subjects met inclusion criteria. Fifty-three percent
      (119) of the IPV perpetuators had a history of TBI, a prevalence significantly
      higher (p < .0001) than estimates of TBI in the general population. The
      prevalence of TBI among perpetuators of IPV appears significantly higher than the
      prevalence of TBI in the general population. To the extent that this association
      is causal, TBI may be a risk factor for interpersonal violence, although
      comparatively few source studies, lack of standardized information about TBI
      severity, and the inability to investigate potential confounding variables
      necessarily limit this conclusion.

PMID- 22467644
TI  - The role of parent-child bonding, attachment, and interpersonal problems in the
      development of deviant sexual fantasies in sexual offenders.
AB  - To understand the origin, development, and functions of deviant sexual fantasy in
      sexual offenders, the present article investigates three areas of the literature
      on sexual offenders (i.e., parent-child relationships, attachment, and
      interpersonal problems), hypothesizing a possible path through which
      dysfunctional parent-child relationships might lead to deviant sexual fantasies.
      The review of the literature provides indirect evidence that an insecure
      attachment style developed in response to dysfunctional parenting practices may
      generate feelings of inadequacy and inferiority to others and a lack of the self
      confidence and social skills to initiate or maintain consensual intimate
      relationships with appropriate others. It is hypothesized that such problems, in
      turn, might promote low levels of intimacy and satisfaction in romantic
      relationships and serious and chronic emotional loneliness, withdrawal, and
      negative attitudes (such as anger and hostility) toward potential partners,
      leading to a progressive retirement from the real world and refuge in an internal
      world of deviant sexual fantasies in order to satisfy attachment-related needs
      for intimacy, emotional closeness, or power. Such a combination of insecure
      attachment, interpersonal problems, and use of deviant sexual fantasies as a
      means to achieve the intimacy, power, or control absent from reality might
      predispose to sexual offending.

PMID- 22467645
TI  - Microfluidic encapsulation of cells in polymer microgels.
AB  - In this Concept article, recent advances in microfluidic platforms for the
      generation of cell-laden hydrogel particles (microgels) are reported. Advances in
      the continuous microfluidic encapsulation of cells in droplets and microgels are
      critically reviewed, and currently used methods for the encapsulation of cells in
      polymer microgels are discussed. An outlook on current applications and future
      directions in this field of research are also presented. This article will be of
      interest to chemists, materials scientists, cell biologists, bioengineers, and
      pharmacologists.

PMID- 22467646
TI  - Immobilization of Escherichia coli containing omega-transaminase activity in
      LentiKats(r).
AB  - Whole Escherichia coli cells overexpressing omega-transaminase (omega-TA) and
      immobilized cells entrapped in LentiKats(r) were used as biocatalysts in the
      asymmetric synthesis of the aromatic chiral amines 1-phenylethylamine (PEA) and 3
      amino-1-phenylbutane (APB). Whole cells were permeabilized with different
      concentrations of cetrimonium bromide (CTAB) and ethanol; the best results were
      obtained with CTAB 0.1% which resulted in an increase in reaction rate by 40%
      compared to the whole cells. The synthesis of PEA was carried out using isopropyl
      amine (IPA) and L-alanine (Ala) as amino donors. Using whole cell biocatalysis,
      the reaction with IPA was one order of magnitude faster than with Ala. No
      reaction was detected when permeabilized E. coli cells containing omega-TA were
      employed using Ala as the amino donor. Additionally, the synthesis of APB from 4
      phenyl-2-butanone and IPA was studied. Whole and permeabilized cells containing
      omega-TA and their immobilized LentiKats(r) counterparts showed similar initial
      reactions rates and yields in the reaction systems, indicating 100% of
      immobilization efficiency (observed activity/activity immobilized) and absence of
      diffusional limitations (due to the immobilization). Immobilization of whole and
      permeabilized cells containing omega-TA in LentiKats(r) allowed improved
      stability as the biocatalyst was shown to be efficiently reused for five reaction
      cycles, retaining around 80% of original activity.

PMID- 22467647
TI  - Depletion of invariant NKT cells reduces inflammation-induced preterm delivery in
      mice.
AB  - This study sought to determine whether invariant NKT (iNKT) cells play an
      essential role in inflammation-induced preterm delivery. Preterm delivery and
      fetal death rates were determined in wild-type (WT) C57BL/6 mice and iNKT cell
      deficient Jalpha18(-/-) mice injected i.p. with LPS. The percentages of decidual
      immune cells, including activated subsets, and costimulatory molecule expression
      were analyzed by flow cytometry. Th1 and Th2 cytokine production in the culture
      supernatants of decidual mononuclear cells was measured by ELISA. To some extent,
      Jalpha18(-/-) mice were resistant to LPS-induced preterm delivery. The
      proportions of decidual CD3(+) and CD49b(+) cells were slightly lower in
      Jalpha18(-/-) mice than in WT Jalpha18(+/+) mice, whereas almost no
      CD3(+)CD49b(+) cells could be found in Jalpha18-null mice. The percentages of
      activated decidual DCs, T cells, and NK cells were significantly lower in LPS
      treated Jalpha18(-/-) mice than in WT mice. The CD40, CD80, and CD86 expression
      levels on decidual CD11c(+) cells from Jalpha18(-/-) mice were also significantly
      lower than in WT mice. Mean concentrations of Th1 cytokines IFN-gamma and IL
      12p70 in the culture supernatants of decidual mononuclear cells from LPS-treated
      Jalpha18(-/-) mice were apparently lower than those of LPS-induced WT mice.
      Additionally, the proportions of activated CD11c(+) cells, CD3(+) cells, and
      CD49b(+) cells in LPS-induced preterm delivery mice were strikingly higher in
      both WT and null mice when compared with the control PBS group and LPS-injected
      but normally delivered mice. Our results suggest that iNKT cells may play an
      essential role in inflammation-induced preterm birth.

PMID- 22467648
TI  - Functional recruitment of the human complement inhibitor C4BP to Yersinia
      pseudotuberculosis outer membrane protein Ail.
AB  - Ail is a 17-kDa chromosomally encoded outer membrane protein that mediates serum
      resistance (complement resistance) in the pathogenic Yersiniae (Yersinia pestis,
      Y. enterocolitica, and Y. pseudotuberculosis). In this article, we demonstrate
      that Y. pseudotuberculosis Ail from strains PB1, 2812/79, and YPIII/pIB1
      (serotypes O:1a, O:1b, and O:3, respectively) can bind the inhibitor of the
      classical and lectin pathways of complement, C4b-binding protein (C4BP). Binding
      was observed irrespective of serotype tested and independently of YadA, which is
      the primary C4BP receptor of Y. enterocolitica. Disruption of the ail gene in Y.
      pseudotuberculosis resulted in loss of C4BP binding. Cofactor assays revealed
      that bound C4BP is functional, because bound C4BP in the presence of factor I
      cleaved C4b. In the absence of YadA, Ail conferred serum resistance to strains
      PB1 and YPIII, whereas serum resistance was observed in strain 2812/79 in the
      absence of both YadA and Ail, suggesting additional serum resistance factors. Ail
      from strain YPIII/pIB1 alone can mediate serum resistance and C4BP binding,
      because its expression in a serum-sensitive laboratory strain of Escherichia coli
      conferred both of these phenotypes. Using a panel of C4BP mutants, each deficient
      in a single complement control protein domain, we observed that complement
      control protein domains 6-8 are important for binding to Ail. Binding of C4BP was
      unaffected by increasing heparin or salt concentrations, suggesting primarily
      nonionic interactions. These results indicate that Y. pseudotuberculosis Ail
      recruits C4BP in a functional manner, facilitating resistance to attack from
      complement.

PMID- 22467649
TI  - Signal integration by Akt regulates CD8 T cell effector and memory
      differentiation.
AB  - During a T cell response, the effector CTL pool contains two cellular subsets:
      short-lived effector cells (SLECs), a majority of which are destined for
      apoptosis, and the memory precursor effector cells, which differentiate into
      memory cells. Understanding the mechanisms that govern the differentiation of
      memory CD8 T cells is of fundamental importance in the development of effective
      CD8 T cell-based vaccines. The strength and nature of TCR signaling, along with
      signals delivered by cytokines like IL-2 and IL-12, influence differentiation of
      SLECs and memory precursor effector cells. A central question is, how are signals
      emanating from multiple receptors integrated and interpreted to define the fate
      of effector CTLs? Using genetic and pharmacological tools, we have identified Akt
      as a signal integrator that links distinct facets of CTL differentiation to the
      specific signaling pathways of FOXO, mTOR, and Wnt/beta-catenin. Sustained Akt
      activation triggered by convergent extracellular signals evokes a transcription
      program that enhances effector functions, drives differentiation of terminal
      effectors, and diminishes the CTLs' potential to survive and differentiate into
      memory cells. Whereas sustained Akt activation severely impaired CD8 T cell
      memory and protective immunity, in vivo inhibition of Akt rescued SLECs from
      deletion and increased the number of memory CD8 T cells. Thus, the cumulative
      strength of convergent signals from signaling molecules such as TCR,
      costimulatory molecules, and cytokine receptors governs the magnitude of Akt
      activation, which in turn controls the generation of long-lived memory cells.
      These findings suggest that therapeutic modulation of Akt might be a strategy to
      augment vaccine-induced immunity.

PMID- 22467650
TI  - Aryl hydrocarbon receptor-mediated induction of EBV reactivation as a risk factor
      for Sjogren's syndrome.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates a variety of biological effects by binding to environmental
      pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin).
      Although numerous animal studies have demonstrated the harmful effects of
      dioxins, it remains controversial whether dioxins pose a risk to human health.
      Enhanced lytic replication of EBV is a risk factor for the development of
      autoimmune diseases and cancers. This study evaluated the possibility that ligand
      activated AhR reactivates EBV. EBV reactivation and AhR transactivation were
      evaluated with luciferase assays. Saliva samples were collected from 19 patients
      with primary Sjogren's syndrome (SS). Control saliva samples were obtained from
      10 healthy individuals and nine patients with severe dry mouth. TCDD enhanced
      BZLF1 transcription, which mediates the switch from the latent to the lytic form
      of EBV infection in EBV-positive B cell lines and in a salivary gland epithelial
      cell line. Moreover, TCDD-induced increases in BZLF1 mRNA and EBV genomic DNA
      levels were confirmed in the B cell lines. Saliva from SS patients activated the
      transcription of both CYP1A1 and BZLF1. Additionally, there was a positive
      correlation between CYP1A1 and BZLF1 promoter activities. AhR ligands elicited
      the reactivation of EBV in activated B cells and salivary epithelial cells, and
      these ligands are involved in SS. Our findings reveal novel aspects of the
      biological effects of dioxin and the AhR-dependent pathogenesis of autoimmune
      diseases.

PMID- 22467651
TI  - Cutting edge: Asymmetric memory T cell division in response to rechallenge.
AB  - Clonal selection of a T cell for use in the immune response appears to
      necessitate proliferative expansion and terminal effector differentiation of some
      cellular progeny, while reserving other progeny as less-differentiated memory
      cells. It has been suggested that asymmetric cell division may promote initial
      cell diversification. Stem cell-like models of adaptive immunity might predict
      that subsequent encounters with a pathogen would evoke reiterative, self
      renewing, asymmetric division by memory T cells. In this study, we show that
      murine memory CD8(+) T cells can divide asymmetrically in response to secondary
      encounter with pathogen. Critical regulators of signaling and transcription are
      partitioned to one side of the mitotic spindle in rechallenged memory T cells,
      and two phenotypically distinct populations of daughter cells are evident from
      the earliest divisions. Memory T cells may thus use asymmetric cell division to
      generate cellular heterogeneity when faced with pathogen rechallenge.

PMID- 22467653
TI  - Uptake of particulate antigens in a nonmammalian lung: phenotypic and functional
      characterization of avian respiratory phagocytes using bacterial or viral
      antigens.
AB  - Major distinctive features of avian lungs are the absence of draining lymph nodes
      and alveoli and alveolar macrophages (MPhs). However, a large network of MPhs and
      dendritic cells (DCs) is present in the mucosa of the larger airways and in the
      linings of the parabronchi. For the modulation of respiratory tract immune
      responses, for example, by vaccination, a better understanding of Ag uptake in
      the chicken respiratory tract is needed. In this study, we provide detailed
      characterization of APCs in chicken lungs, including their functional in vivo
      activities as measured by the uptake of fluorescently labeled 1-MUm beads that
      are coated with either LPS or inactivated avian influenza A virus (IAV) mimicking
      the uptake of bacterial or viral Ag. We identified different subsets of MPhs and
      DCs in chicken lungs, based on the expression of CD11, activation markers, and
      DEC205. In vivo uptake of LPS- and IAV-beads resulted in an increased percentage
      MHC class II(+) (MHC II(+)) cells and in the upregulation of CD40. The uptake of
      LPS-beads resulted in the upregulation of CD80 and MHC II on the cell surface,
      suggesting either uptake of LPS- and IAV-beads by different subsets of phagocytic
      cells or LPS-mediated differential activation. Differences in phagosomal
      acidification indicated that in chicken lungs the MHC II(+) and CD80(+) bead(+)
      cell population includes DCs and that a large proportion of beads was taken up by
      MPhs. LPS-bead(+) cells were present in BALT, suggesting local induction of
      immune responses. Collectively, we characterized the uptake of Ags by phagocytes
      in the respiratory tract of chickens.

PMID- 22467652
TI  - The utility and limitations of current Web-available algorithms to predict
      peptides recognized by CD4 T cells in response to pathogen infection.
AB  - The ability to track CD4 T cells elicited in response to pathogen infection or
      vaccination is critical because of the role these cells play in protective
      immunity. Coupled with advances in genome sequencing of pathogenic organisms,
      there is considerable appeal for implementation of computer-based algorithms to
      predict peptides that bind to the class II molecules, forming the complex
      recognized by CD4 T cells. Despite recent progress in this area, there is a
      paucity of data regarding the success of these algorithms in identifying actual
      pathogen-derived epitopes. In this study, we sought to rigorously evaluate the
      performance of multiple Web-available algorithms by comparing their predictions
      with our results--obtained by purely empirical methods for epitope discovery in
      influenza that used overlapping peptides and cytokine ELISPOTs--for three
      independent class II molecules. We analyzed the data in different ways, trying to
      anticipate how an investigator might use these computational tools for epitope
      discovery. We come to the conclusion that currently available algorithms can
      indeed facilitate epitope discovery, but all shared a high degree of false
      positive and false-negative predictions. Therefore, efficiencies were low. We
      also found dramatic disparities among algorithms and between predicted IC(50)
      values and true dissociation rates of peptide-MHC class II complexes. We suggest
      that improved success of predictive algorithms will depend less on changes in
      computational methods or increased data sets and more on changes in parameters
      used to "train" the algorithms that factor in elements of T cell repertoire and
      peptide acquisition by class II molecules.

PMID- 22467654
TI  - Herpes simplex virus antigens directly activate NK cells via TLR2, thus
      facilitating their presentation to CD4 T lymphocytes.
AB  - NK cells infiltrate human herpetic lesions, but their role has been
      underexplored. HSV can stimulate innate immune responses via surface TLR2, which
      is expressed on monocyte-derived dendritic cells (DCs) and NK cells. In this
      study, UV-inactivated HSV1/2 and immunodominant HSV2 glycoprotein D peptides
      conjugated to the TLR2 agonist dipalmitoyl-S-glyceryl cysteine stimulated CD4 T
      lymphocyte IFN-gamma responses within PBMCs or in coculture with monocyte-derived
      DCs. NK cells contributed markedly to the PBMC responses. Furthermore, NK cells
      alone were activated directly by both Ags, also upregulating HLA-DR and HLA-DQ
      and then they activated autologous CD4 T lymphocytes. Using Transwells, Ag
      stimulated NK cells and CD4 T lymphocytes were shown to interact through both
      cell-to-cell contact and cytokines, differing in relative importance in different
      donors. A distinct immunological synapse between Ag-stimulated NK cells and CD4 T
      lymphocytes was observed, indicating the significance of their cell-to-cell
      contact. A large proportion (57%) of NK cells was also in contact with CD4 T
      lymphocytes in the dermal infiltrate of human recurrent herpetic lesions. Thus,
      NK cells stimulated by TLR2-activating HSV Ags can present Ag alone or augment
      the role of DCs in vitro and perhaps in herpetic lesions or draining lymph nodes.
      In addition to DCs, NK cells should be considered as targets for adjuvants during
      HSV vaccine development.

PMID- 22467655
TI  - NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a
      mouse model of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial
      and perivascular inflammation and largely irreversible airflow obstruction. Acute
      disease exacerbations, due frequently to viral infections, lead to enhanced
      disease symptoms and contribute to long-term progression of COPD pathology.
      Previously, we demonstrated that NK cells from cigarette smoke (CS)-exposed mice
      exhibit enhanced effector functions in response to stimulating cytokines or TLR
      ligands. In this article, we show that the activating receptor NKG2D is a key
      mediator for CS-stimulated NK cell hyperresponsiveness, because CS-exposed NKG2D
      deficient mice (Klrk1(-/-)) did not exhibit enhanced effector functions as
      assessed by cytokine responsiveness. NK cell cytotoxicity against MHC class I
      deficient targets was not affected in a COPD model. However, NK cells from CS
      exposed mice exhibit greater cytotoxic activity toward cells that express the
      NKG2D ligand RAET1epsilon. We also demonstrate that NKG2D-deficient mice exhibit
      diminished airway damage and reduced inflammation in a model of viral COPD
      exacerbation, which do not affect viral clearance. Furthermore, adoptive transfer
      of NKG2D(+) NK cells into CS-exposed, influenza-infected NKG2D-deficient mice
      recapitulated the phenotypes observed in CS-exposed, influenza-infected wild-type
      mice. Our findings indicate that NKG2D stimulation during long-term CS exposure
      is a central pathway in the development of NK cell hyperresponsiveness and
      influenza-mediated exacerbations of COPD.

PMID- 22467656
TI  - Aberrant macrophages mediate defective kidney repair that triggers nephritis in
      lupus-susceptible mice.
AB  - CSF-1, required for macrophage (Mo) survival, proliferation, and activation, is
      upregulated in the tubular epithelial cells (TECs) during kidney inflammation.
      CSF-1 mediates Mo-dependent destruction in lupus-susceptible mice with nephritis
      and, paradoxically, Mo-dependent renal repair in lupus-resistant mice after
      transient ischemia/reperfusion injury (I/R). We now report that I/R leads to
      defective renal repair, nonresolving inflammation, and, in turn, early-onset
      lupus nephritis in preclinical MRL/MpJ-Faslpr/Fas(lpr) mice (MRL-Fas(lpr) mice).
      Moreover, defective renal repair is not unique to MRL-Fas(lpr) mice, as flawed
      healing is a feature of other lupus-susceptible mice (Sle 123) and MRL mice
      without the Fas(lpr) mutation. Increasing CSF-1 hastens renal healing after I/R
      in lupus-resistant mice but hinders healing, exacerbates nonresolving
      inflammation, and triggers more severe early-onset lupus nephritis in MRL
      Fas(lpr) mice. Probing further, the time-related balance of M1 "destroyer" Mo
      shifts toward the M2 "healer" phenotype in lupus-resistant mice after I/R, but M1
      Mo continue to dominate in MRL-Fas(lpr) mice. Moreover, hypoxic TECs release
      mediators, including CSF-1, that are responsible for stimulating the expansion of
      M1 Mo inherently poised to destroy the kidney in MRL-Fas(lpr) mice. In
      conclusion, I/R induces CSF-1 in injured TECs that expands aberrant Mo (M1
      phenotype), mediating defective renal repair and nonresolving inflammation, and
      thereby hastens the onset of lupus nephritis.

PMID- 22467657
TI  - Colonic epithelial cells express specific ligands for mucosal macrophage
      immunosuppressive receptors siglec-7 and -9.
AB  - Immune cells are known to express specific recognition molecules for cell surface
      glycans. However, mechanisms involved in glycan-mediated cell-cell interactions
      in mucosal immunity have largely been left unaccounted for. We found that several
      glycans preferentially expressed in nonmalignant colonic epithelial cells serve
      as ligands for sialic acid-binding Ig-like lectins (siglecs), the
      immunosuppressive carbohydrate-recognition receptors carried by immune cells. The
      siglec ligand glycans in normal colonic epithelial cells included disialyl
      Lewis(a), which was found to have binding activity to both siglec-7 and -9, and
      sialyl 6-sulfo Lewis(x), which exhibited significant binding to siglec-7.
      Expression of these siglec-7/-9 ligands was impaired upon carcinogenesis, and
      they were replaced by cancer-associated glycans sialyl Lewis(a) and sialyl
      Lewis(x), which have no siglec ligand activity. When we characterized immune
      cells expressing siglecs in colonic lamina propriae by flow cytometry and
      confocal microscopy, the majority of colonic stromal immune cells expressing
      siglec-7/-9 turned out to be resident macrophages characterized by low expression
      of CD14/CD89 and high expression of CD68/CD163. A minor subpopulation of CD8(+) T
      lymphocytes also expressed siglec-7/-9. Siglec-7/-9 ligation suppressed LPS
      induced cyclooxygenase-2 expression and PGE(2) production by macrophages. These
      results suggest that normal glycans of epithelial cells exert a suppressive
      effect on cyclooxygenase-2 expression by resident macrophages, thus maintaining
      immunological homeostasis in colonic mucosal membranes. Our results also imply
      that loss of immunosuppressive glycans by impaired glycosylation during colonic
      carcinogenesis enhances inflammatory mediator production.

PMID- 22467658
TI  - Differential transcription factor use by the KIR2DL4 promoter under constitutive
      and IL-2/15-treated conditions.
AB  - KIR2DL4 is unique among human KIR genes in expression, cellular localization,
      structure, and function, yet the transcription factors required for its
      expression have not been identified. Using mutagenesis, EMSA, and cotransfection
      assays, we identified two redundant Runx binding sites in the 2DL4 promoter as
      essential for constitutive 2DL4 transcription, with contributions by a cyclic AMP
      response element (CRE) and initiator elements. IL-2- and IL-15-stimulated human
      NK cell lines increased 2DL4 promoter activity, which required functional Runx,
      CRE, and Ets sites. Chromatin immunoprecipitation experiments show that Runx3 and
      Ets1 bind the 2DL4 promoter in situ. 2DL4 promoter activity had similar
      transcription factor requirements in T cells. Runx, CRE, and Ets binding motifs
      are present in 2DL4 promoters from across primate species, but other postulated
      transcription factor binding sites are not preserved. Differences between 2DL4
      and clonally restricted KIR promoters suggest a model that explains the unique
      2DL4 expression pattern in human NK cells.

PMID- 22467659
TI  - Galectin-1 reduces the severity of herpes simplex virus-induced ocular
      immunopathological lesions.
AB  - Stromal keratitis is a chronic immunopathological lesion of the eye caused by HSV
      1 infection that can result in blindness. Because the inflammatory lesions are
      primarily orchestrated by Th1 cells, and to a lesser extent by Th17 cells,
      inhibiting their activity represents a useful form of therapy. In this study we
      evaluated the therapeutic potential of galectin-1 (gal-1), an endogenous lectin
      that in some autoimmune diseases was shown to suppress the functions of Th1 and
      Th17 cells. Treatment was begun at different times after ocular infection with
      HSV and the outcome was assessed clinically as well as for effects on various
      immune parameters. Treatment with recombinant gal-1 significantly diminished
      stromal keratitis lesion severity and the extent of corneal neovascularization.
      Treated mice had reduced numbers of IFN-gamma- and IL-17-producing CD4(+) T
      cells, as well as neutrophil infiltration in the cornea. Furthermore, disease
      severity was greater in gal-1 knockout mice compared with their wild-type
      counterparts. The many effects of gal-1 treatment include reduction in the
      production of proinflammatory cytokines and chemokines, increased production of
      IL-10, and inhibitory effects on molecules involved in neovascularization. To our
      knowledge, our findings are the first to show that gal-1 treatment represents a
      useful approach to control lesion severity in a virally induced
      immunopathological disease.

PMID- 22467660
TI  - Cutting edge: Inhibition of IL-6 trans-signaling protects from malaria-induced
      lethality in mice.
AB  - Circulating IL-6 levels correlate with the severity of blood-stage malaria in
      humans and mouse models, but the impact of IL-6 classic signaling through
      membrane IL-6Ralpha, as well as IL-6 trans-signaling through soluble IL-6Ralpha,
      on the outcome of malaria has remained unknown. In this study, we created IL
      6Ralpha-deficient mice that exhibit a 50% survival of otherwise lethal blood
      stage malaria of the genus Plasmodium chabaudi. Inducing IL-6 trans-signaling by
      injection of mouse recombinant soluble IL-6Ralpha in IL-6Ralpha-deficient mice
      restores the lethal outcome to malaria infection. In contrast, inhibition of IL-6
      trans-signaling via injection of recombinant sGP130Fc protein in control mice
      results in a 40% survival rate. Our data demonstrate that IL-6 trans-signaling,
      rather than classic IL-6 signaling, contributes to malaria-induced lethality in
      mice, preceded by an increased inflammatory response. Therefore, inhibition of IL
      6 trans-signaling may serve as a novel promising therapeutic basis to combat
      malaria.

PMID- 22467661
TI  - Human Vgamma9Vdelta2 T cells specifically recognize and kill acute myeloid
      leukemic blasts.
AB  - Vgamma9Vdelta2 T cells are attractive candidates for antileukemic activity. The
      analysis of Vgamma9Vdelta2 T cells in newly diagnosed acute myeloid leukemia
      (AML) patients revealed that their absolute cell numbers were normal in the blood
      as well as in the bone marrow but showed a striking imbalance in the
      differentiation subsets, with preponderance of the effector memory population.
      This unusual phenotype was restored after removal of leukemic cells in patients,
      which reached complete remission after chemotherapy, suggesting that leukemic
      cells might be involved in the alteration of gammadelta T cell development in
      AML. Accordingly, coculture between AML cells and Vgamma9Vdelta2 T cells induced
      selection of effector cells. In accordance with their effector memory status, in
      vitro proliferation of Vgamma9Vdelta2 T cells was reduced compared with normal
      controls. Nevertheless, Vgamma9Vdelta2 T cells efficiently killed autologous AML
      blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed
      by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent.
      Using a xenotransplantation murine model, we showed that Vgamma9Vdelta2 T cells
      homed to the bone marrow in close proximity of engrafted leukemic cells and
      enhanced survival. These data demonstrate that Vgamma9Vdelta2 T cells are endowed
      with the ability to interact with and eradicate AML blasts both in vitro and in a
      mouse model. Collectively, our data revealed that Vgamma9Vdelta2 T cells have a
      potent antileukemic activity provided that optimal activation is achieved, such
      as with synthetic TCR agonists. This study enhances the interest of these cells
      for therapeutic purposes such as AML treatment.

PMID- 22467662
TI  - Criteria for solid recovered fuels as a substitute for fossil fuels--a review.
AB  - The waste treatment, particularly the thermal treatment of waste has changed
      fundamentally in the last 20 years, i.e. from facilities solely dedicated to the
      thermal treatment of waste to facilities, which in addition to that ensure the
      safe plant operation and fulfill very ambitious criteria regarding emission
      reduction, resource recovery and energy efficiency as well. Therefore this
      contributes to the economic use of raw materials and due to the energy recovered
      from waste also to the energy provision. The development described had the
      consequence that waste and solid recovered fuels (SRF) has to be evaluated based
      on fuel criteria as well. Fossil fuels - coal, crude oil, natural gas etc. have
      been extensively investigated due to their application in plants for energy
      conversion and also due to their use in the primary industry. Thereby depending
      on the respective processes, criteria on fuel technical properties can be
      derived. The methods for engineering analysis of regular fuels (fossil fuels) can
      be transferred only partially to SRF. For this reason methods are being developed
      or adapted to current analytical methods for the characterization of SRF. In this
      paper the possibilities of the energetic utilization of SRF and the
      characterization of SRF before and during the energetic utilization will be
      discussed.

PMID- 22467663
TI  - An assessment of community capacity to prevent adolescent alcohol consumption.
AB  - To effectively address the issue of youth alcohol use, communities need to have
      sufficient infrastructure and capacity in place to operate effective prevention
      programs. This study evaluates community capacity in the state of Hawai'i, using
      the Capacity Assessment Survey administered to stakeholders in the youth alcohol
      prevention system. Capacity is quantified with gap scores, which measure the
      discrepancy between an agency's performance of an attribute and the attribute's
      relative importance. Six assessment areas, termed capacity domains, are defined.
      Results are given for each county and the state overall. Based on these results,
      communities need to prioritize capacity-building efforts specifically in the
      domains of effectiveness, funding/resource availability, and sustainability.
      Organization, workforce skills/knowledge, and cultural competency were
      categorized as relative strengths in comparison, but gap scores are nevertheless
      significantly greater than 0 ("ideal"; p < .001), indicating these areas need
      improvement as well. Suggestions for improvement in each capacity domain are
      given. This assessment is the first step in a five-step planning process to
      implement youth alcohol prevention programs in communities in Hawai'i.

PMID- 22467664
TI  - Integrating evidence-based tobacco cessation interventions in free medical
      clinics: opportunities and challenges.
AB  - BACKGROUND: Free medical clinics serve a critical role in health care delivery of
      America's uninsured population, who are less likely to receive tobacco cessation
      counseling and 11/2 times more likely than the general population to use tobacco.
      The authors evaluate the opportunities for and challenges to implementing the
      U.S. Public Health Service Guidelines for tobacco cessation in free clinics.
      METHODS: Six free clinics participated in this pilot study. Five objectives were
      targeted: implementation of a tobacco user identification system, education of
      all clinic staff and volunteers, dedication of a program champion, use of
      evidence-based treatment, and creation of a supportive environment that
      reinforces provider behavior. Key informant interviews and focus group data were
      used to describe the opportunities and barriers of implementing the Public Health
      Service Guidelines. RESULTS: All clinics adopted a user identification system,
      dedicated a program champion, adopted evidence-based counseling, and created an
      environment conducive for cessation. Common challenges included getting
      volunteers to attend on-site training programs, accessing nicotine replacement
      therapy, and promoting Quit Line usage, all of which are part of evidence-based
      treatment. CONCLUSION: With more than 1,200 free clinics nationwide, it is very
      important to understand the opportunities and barriers of implementing tobacco
      cessation services and systems in free clinics.

PMID- 22467665
TI  - The impact of diabetes mellitus on prognosis of early breast cancer in Asia.
AB  - BACKGROUND: Diabetes mellitus (DM) has been implicated in influencing the
      survival duration of patients with breast cancer. However, less is known about
      the impact of DM and other comorbidities on the breast cancer-specific survival
      (BCS) and overall survival (OS) outcomes of Asian patients with early-stage
      breast cancer. PATIENTS AND METHODS: The characteristics of female patients with
      newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer
      Registry database for 2003-2004. DM status and other comorbidities were retrieved
      from Taiwan's National Health Insurance database. The BCS and OS times of
      patients according to DM status were estimated via the Kaplan-Meier method. Cox's
      proportional hazard model was used to estimate adjusted hazard ratios (HRs) for
      the effects of DM, comorbidities, and other risk factors on mortality. RESULTS:
      In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5
      year BCS and OS rates were significantly greater in DM patients than in non-DM
      patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting
      for clinicopathologic variables and comorbidities, DM remained an independent
      predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times.
      Subgroup analyses also demonstrated a consistent prognostic influence of DM
      across different groups. CONCLUSION: In Asian patients with early-stage breast
      cancer, DM is an independent predictor of lower BCS and OS rates, even after
      adjusting for other comorbidities. The integration of DM care as part of the
      continuum of care for early-stage breast cancer should be emphasized.

PMID- 22467666
TI  - Phase II study of bevacizumab in combination with trastuzumab and capecitabine as
      first-line treatment for HER-2-positive locally recurrent or metastatic breast
      cancer.
AB  - We report the first results from a phase II, open-label study designed to
      evaluate the efficacy and safety of bevacizumab in combination with trastuzumab
      and capecitabine as first-line therapy for human epidermal growth factor receptor
      (HER)-2-positive locally recurrent (LR) or metastatic breast cancer (MBC).
      Patients were aged >=18 years with confirmed breast adenocarcinoma, measurable
      LR/MBC and documented HER-2-positive disease. Patients received bevacizumab (15
      mg/kg on day 1) plus trastuzumab (8 mg/kg on day 1 of cycle 1, 6 mg/kg on day 1
      of each subsequent cycle) plus capecitabine (1,000 mg/m2 twice daily, days 1-14)
      every 3 weeks until disease progression, unacceptable toxicity, or consent
      withdrawal. Eighty-eight patients were enrolled; 40 (46%) are still on study
      treatment. The median follow-up was 8.8 months (range, 0.9-17.1 months). The
      overall response rate, the primary endpoint, was 73% (95% confidence interval
      [CI], 62%-82%), comprising 7% complete and 66% partial responses. The median
      progression-free survival interval was 14.4 months (95% CI, 10.4 months to not
      reached [NR]), with 35 events. The median time to progression was 14.5 months
      (95% CI, 10.5 months to NR), with 33 events. Treatment was well tolerated; main
      side effects were grade 3 hand-foot syndrome (22%), grade >=3 diarrhea (9%), and
      grade >=3 hypertension (7%). Overall, 44% of patients experienced grade >=3
      treatment-related adverse events and 13 patients discontinued capecitabine
      because of toxicity, but continued with bevacizumab and trastuzumab. Heart
      failure was seen in two patients. The combination of bevacizumab, trastuzumab,
      and capecitabine was clinically active as first-line therapy for patients with
      HER-2-positive MBC, with an acceptable safety profile and no unexpected
      toxicities.

PMID- 22467667
TI  - Phencyclidine-induced decrease of synaptic connectivity via inhibition of BDNF
      secretion in cultured cortical neurons.
AB  - Repeated administration of phencyclidine (PCP), a noncompetitive N-methyl-D
      aspartate (NMDA) receptor blocker, produces schizophrenia-like behaviors in
      humans and rodents. Although impairment of synaptic function has been implicated
      in the effect of PCP, the molecular mechanisms have not yet been elucidated.
      Considering that brain-derived neurotrophic factor (BDNF) plays an important role
      in synaptic plasticity, we examined whether exposure to PCP leads to impaired
      BDNF function in cultured cortical neurons. We found that PCP caused a transient
      increase in the level of intracellular BDNF within 3 h. Despite the increased
      intracellular amount of BDNF, activation of Trk receptors and downstream
      signaling cascades, including MAPK/ERK1/2 and PI3K/Akt pathways, were decreased.
      The number of synaptic sites and expression of synaptic proteins were decreased
      48 h after PCP application without any impact on cell viability. Both
      electrophysiological and biochemical analyses revealed that PCP diminished
      glutamatergic neurotransmission. Furthermore, we found that the secretion of BDNF
      from cortical neurons was suppressed by PCP. We also confirmed that PCP-caused
      downregulation of Trk signalings and synaptic proteins were restored by exogenous
      BDNF application. It is possible that impaired secretion of BDNF and subsequent
      decreases in Trk signaling are responsible for the loss of synaptic connections
      caused by PCP.

PMID- 22467668
TI  - Excess deaths associated with tigecycline after approval based on noninferiority
      trials.
AB  - BACKGROUND: On the basis of noninferiority trials, tigecycline received Food and
      Drug Administration (FDA) approval in 2005. In 2010, the FDA warned in a safety
      communication that tigecycline was associated with an increased risk of death.
      METHODS: PubMed, EMBASE, Scopus, and ClinicalTrials.gov were searched using the
      terms "tigecycline" and "randomized controlled trial (RCT)" through April 2011.
      Excess deaths and noncure rates for both approved and nonapproved indications
      were examined using meta-analysis. RESULTS: Ten published and 3 unpublished
      studies met inclusion criteria (N = 7434). No significant heterogeneity was seen
      for mortality (I(2 )= 0%; P = .99) or noncure rates (I(2 )= 25%; P = .19). Across
      randomized controlled trials, tigecycline was associated with increased mortality
      (risk difference [RD], 0.7%; 95% confidence interval [CI], 0.1%-1.2%; P = .01)
      and noncure rates (RD, 2.9%; 95% CI, 0.6%-5.2%; P = .01). Effects were not
      isolated to type of infection or comparator antibiotic regimen, and the impact on
      survival remained significant when limited to trials of approved indications (I(2
      )= 0%; RD, 0.6%; P = .04). A pooled analysis of the 5 trials completed by early
      2005 before tigecycline was approved would have demonstrated a similar harmful
      effect of tigecycline on survival (I(2 )= 0%; RD, 0.7%; P = .06). CONCLUSIONS:
      Pooling noninferiority studies to examine survival may help ensure the safety and
      efficacy of new antibiotics. The association of tigecycline with excess deaths
      and noncure includes indications for which it is approved and marketed.
      Tigecycline cannot be relied on in serious infections.

PMID- 22467669
TI  - Infective dermatitis associated with human T-cell lymphotropic virus type 1:
      evaluation of 42 cases observed in Bahia, Brazil.
AB  - BACKGROUND: Infective dermatitis associated with human T-cell lymphotropic virus
      type 1 (HTLV-1; IDH) is a chronic recurrent eczema affecting HTLV-1-infected
      children. The epidemiological and dermatological characteristics of IDH are
      described, and their principal diagnostic criteria are reevaluated. METHODS:
      Forty-two patients were included: 40 patients serologically positive for HTLV-1
      and 2 seronegative patients who tested positive in polymerase chain reaction
      (PCR) assays. RESULTS: The mean age at onset of the disease was 2.6 +/- 2.4 years
      (range, 2 months-11 years). The mean duration of breast-feeding was 24.2 months.
      The lesions were erythematous, scaly, and crusted, always affecting the scalp and
      retroauricular regions. Crusting of the nostrils was observed in 64.3% of the
      patients. Of the 36 patients followed up, 23 had the active disease. The age at
      which IDH disappeared in the others was 10-20 years. CONCLUSIONS: The onset of
      IDH may occur earlier than reported in the literature. The scalp and
      retroauricular regions are always affected, and lesions are invariably present in
      >=3 areas. Crusting of the nostrils cannot be considered an obligatory factor for
      the diagnosis of IDH. The recurring nature of IDH was a characteristic found in
      all cases. Patients with classic IDH lesions who are serologically negative
      should be investigated by PCR. Therefore, the indispensable criteria for
      diagnosis are (1) presence of erythematous-scaly, exudative, and crusted lesions
      involving >=3 areas, including the scalp and retroauricular regions; (2)
      recurring nature of the lesions; and (3) a finding of HTLV-1 infection by
      serology or molecular biology.

PMID- 22467670
TI  - Meta-analysis of clinical studies supports the pharmacokinetic variability
      hypothesis for acquired drug resistance and failure of antituberculosis therapy.
AB  - BACKGROUND: Using hollow-fiber tuberculosis studies, we recently demonstrated
      that nonadherence is not a significant factor for ADR and that therapy failure
      only occurs after a large proportion of doses are missed. Computer-aided clinical
      trial simulations have suggested that isoniazid and rifampin pharmacokinetic
      variability best explained poor outcomes. We were interested in determining
      whether isoniazid pharmacokinetic variability was associated with either
      microbiological failure or ADR in the clinic. METHODS: Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses guidelines were followed. Prospective,
      randomized, controlled clinical trials that reported isoniazid acetylation status
      and microbiological outcomes were selected. The main effects examined were
      microbiological sputum conversion, ADR, and relapse. Effect size was expressed as
      pooled risk ratios (RRs) comparing rapid with slow acetylators. RESULTS: Thirteen
      randomized studies with 1631 rapid acetylators and 1751 slow acetylators met
      inclusion and exclusion criteria. Rapid acetylators were more likely than slow
      acetylators to have microbiological failure (RR, 2.0; 95% confidence interval
      [CI], 1.5-2.7), ADR (RR, 2.0; CI, 1.1-3.4), and relapse (RR, 1.3; CI, .9-2.0).
      Higher failure rates were encountered even in drug regimens comprising >3
      antibiotics. No publication bias or small-study effects were observed for the
      outcomes evaluated. CONCLUSIONS: Pharmacokinetic variability to a single drug in
      the regimen is significantly associated with failure of therapy and ADR in
      patients. This suggests that individualized dosing for tuberculosis may be more
      effective than standardized dosing, which is prescribed in directly observed
      therapy programs.

PMID- 22467671
TI  - Editorial commentary: Asking the right questions: morbidity, mortality, and
      measuring what's important in unbiased evaluations of antimicrobials.

PMID- 22467672
TI  - Editorial commentary: pharmacokinetic variability and tuberculosis treatment
      outcomes, including acquired drug resistance.

PMID- 22467673
TI  - Diastolic electromechanical coupling: association of the ECG T-peak to T-end
      interval with echocardiographic markers of diastolic dysfunction.
AB  - BACKGROUND: Electromechanical coupling, a well-described phenomenon in systolic
      dysfunction, has not been well studied in diastole. We hypothesized that the ECG
      T-peak to T-end (TpTe) interval, representing transmural dispersion of
      repolarization, is associated with echocardiographic markers of diastolic
      dysfunction (DD). METHODS AND RESULTS: We performed a prospective, cross
      sectional study of the association between TpTe and markers of DD in 84
      consecutive, unselected patients referred for exercise echocardiography. We
      systematically measured TpTe on the resting ECG, and we performed comprehensive
      assessment of DD at rest and at peak stress. ECGs and echocardiograms were
      analyzed independently, blinded to each other and to all clinical data. By
      univariable analysis, increased TpTe was associated with older age, increased
      E/e' ratio, and DD (P<0.05 for all associations after correcting for multiple
      comparisons). Increased TpTe was inversely associated with reduced tissue Doppler
      e' velocity, a marker of DD (R=-0.66, P<0.0001). This association persisted after
      adjusting for age, QTc, exercise-induced wall motion abnormalities, and left
      ventricular mass index (beta=-0.41 [95% confidence interval, -0.70 to -0.12] cm/s
      per 10-ms increase in TpTe; P=0.006). Baseline TpTe was also independently
      associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval,
      1.4-10.7]; P=0.009) and peak exercise E/e' ratio (P<0.0001). CONCLUSIONS:
      Increased TpTe is associated with both resting and exercise-induced DD.
      Electromechanical coupling may represent a pathophysiologic link between
      electrical transmural dispersion of repolarization and abnormal myocardial
      relaxation, and may be a novel therapeutic target.

PMID- 22467674
TI  - Chloroquine terminates stretch-induced atrial fibrillation more effectively than
      flecainide in the sheep heart.
AB  - BACKGROUND: Blockade of inward-rectifier K+ channels by chloroquine terminates
      reentry in cholinergic atrial fibrillation (AF). However, it is unknown whether
      inward-rectifier K+ channels and reentry are also important in maintaining
      stretch-induced AF (SAF). We surmised that reentry underlies SAF, and that
      abolishing reentry with chloroquine terminates SAF more effectively than
      traditional Na+-channel blockade by flecainide. METHODS AND RESULTS: Thirty
      Langendorff-perfused sheep hearts were exposed to acute and continuous atrial
      stretch, and mapped optically and electrically. AF dynamics were studied under
      control and during perfusion of either chloroquine (4 umol/L, n=7) or flecainide
      (2-4 umol/L, n=5). Chloroquine increased rotor core size and decreased reentry
      frequency from 10.6+/-0.7 Hz in control to 6.3+/-0.7 Hz (P<0.005) just before
      restoring sinus rhythm (7/7). Flecainide had lesser effects on core size and
      reentry frequency than chloroquine and did not restore sinus rhythm (0/5).
      Specific IKr blockade by E-4031 (n=7) did not terminate AF when frequency values
      were >8 Hz. During pacing (n=11), flecainide reversibly reduced conduction
      velocity (~30% at cycle length 300, 250, and 200 ms; P<0.05) to a larger extent
      than chloroquine (11% to 19%; cycle length, 300, 250, and 200 ms; P<0.05).
      Significant action potential duration prolongation was demonstrable only for
      chloroquine at cycle length 300 (12%) and cycle length 250 ms (9%) (P<0.05).
      CONCLUSIONS: Chloroquine is more effective than flecainide in terminating SAF in
      isolated sheep hearts by significantly increasing core size and decreasing
      reentry frequency. Chloroquine's effectiveness may be explained by its inward
      rectifier K+ channel blockade profile and suggest that reentry is important to
      maintain acute SAF.

PMID- 22467675
TI  - Prognostic implication of appropriateness criteria for pharmacologic stress
      echocardiography performed in an outpatient clinic [corrected].
AB  - BACKGROUND: Although appropriateness criteria for stress echocardiography have
      been developed to deliver high-quality care, the prognostic impact of these
      criteria remains undefined. Therefore, we sought to assess the prognostic
      implication of the American College of Cardiology/American Society of
      Echocardiography appropriateness criteria for pharmacological stress echo in a
      cohort of ambulatory patients. METHODS AND RESULTS: The study population
      consisted of 1552 ambulatory patients who underwent pharmacological (752
      dobutamine, 800 dipyridamole) stress echo for the evaluation of known (n=549) or
      suspected (n=1003) coronary artery disease at a single cardiology center.
      Patients were followed up for a median of 36 months. Indications were determined
      for consecutive studies by 2 reviewers and categorized as follows: 984 (63%)
      patients had appropriate, 145 (9%) uncertain, and 423 (27%) inappropriate
      indication for stress echo. Ischemia was present in 15% of patients with
      appropriate, 8% of those with uncertain, and 5% of those with inappropriate
      indication (P<0.0001). During follow-up, 146 events (89 deaths, 57 nonfatal
      infarctions) occurred. Annual event rate associated with appropriate, uncertain,
      and inappropriate study was 3.1%, 3.8%, and 1.3%, respectively. The abnormal test
      result in patients with appropriate, uncertain, and inappropriate study was
      associated with 5.0%, 5.6%, and 1.8% annual event rate, respectively, exerting an
      independent value only in the appropriate and uncertain subset. CONCLUSIONS:
      Inappropriate indication for pharmacological stress echo is common, being
      documented in about 1 of 4 patients evaluated in an ambulatory setting, and is
      associated with lower rate of positive results and better survival as compared
      with appropriate and uncertain indication.

PMID- 22467676
TI  - Editorial: phagocytic B cells: deja vu all over again?

PMID- 22467677
TI  - Editorial: beta-glucans: going through GM-CSF to get to dectin.

PMID- 22467678
TI  - Retraction.

PMID- 22467679
TI  - Tumor infiltrating immune cells and outcome of Merkel cell carcinoma: a
      population-based study.
AB  - PURPOSE: Merkel cell carcinoma (MCC) is a rare skin cancer that often harbors
      Merkel cell polyomavirus (MCPyV) DNA. The clinical importance of intratumoral
      immune cells and their associations with MCPyV infection are poorly understood.
      EXPERIMENTAL DESIGN: We identified T lymphocytes (CD3-positive cells), T-cell
      subsets (CD4, CD8, and FoxP3-positive cells), natural killer cells (small CD16
      positive cells), and macrophages (CD68 and CD163-positive cells) in tumors of 116
      individuals diagnosed with MCC in Finland from 1979 to 2004 using
      immunohistochemistry and detected MCPyV DNA with quantitative PCR. The
      associations between immune cell counts, MCPyV DNA, patient and tumor
      characteristics, and patient outcome were examined. RESULTS: MCPyV DNA-positive
      cancers contained higher numbers of CD3(+), CD8(+), CD16(+), FoxP3(+), and
      CD68(+) cells as compared with MCPyV DNA-negative carcinomas (all P values <
      0.05). High intratumoral numbers of CD3(+), CD8(+), or FoxP3(+) cells, and high
      CD8(+)/CD4(+) or FoxP3(+)/CD4(+) ratios, were significantly associated with
      favorable overall survival. Individuals with a high tumor CD3(+) count had
      metastases less often and survived longer, irrespective of the tumor MCPyV
      status. Tumor CD3(+) count and MCPyV DNA status had independent influence on
      survival in a Cox multivariable model that also included presence of locoregional
      metastases at diagnosis and gender as covariates. CONCLUSIONS: High intratumoral
      T-lymphocyte counts are associated with favorable survival in MCC. Although the
      numbers of T cells are generally higher in MCPyV-positive than in MCPyV-negative
      MCC, high intratumoral T-cell counts are also associated with favorable survival
      in MCPyV-negative MCC.

PMID- 22467680
TI  - The effects of chemotherapy on cognitive function in a mouse model: a prospective
      study.
AB  - PURPOSE: Clinical studies indicate that up to 70% of patients with cancer who
      receive chemotherapy experience cognitive impairment. The present study used a
      prospective longitudinal design to assess short- and long-term effects of
      commonly used anticancer drugs on cognitive performance in a mouse model.
      EXPERIMENTAL DESIGN: Normal mice received three weekly injections of a
      combination of methotrexate + 5-fluorouracil (CHEMO group) or an equal volume of
      saline (SAL group). Cognitive tests, measuring different aspects of learning and
      memory, were administered before treatment, immediately after treatment, and
      three months later. Structural MRI scanning was conducted at each stage of
      cognitive testing. RESULTS: The CHEMO group exhibited deficits on cognitive tasks
      acquired pretreatment [spatial memory, nonmatching-to-sample (NMTS) learning, and
      delayed NMTS], as well as impaired new learning on two tasks (conditional
      associative learning, discrimination learning) introduced posttreatment.
      Consistent with clinical evidence, cognitive deficits were pronounced on tests
      that are sensitive to hippocampal and frontal lobe dysfunction, but the CHEMO
      group's poor performance on the discrimination learning problem suggests that
      impairment is more widespread than previously thought. Cognitive deficits
      persisted for at least three months after treatment but some recovery was noted,
      particularly on tests thought to be under frontal lobe control. The MRI tests did
      not detect brain changes that could be attributed to treatment. CONCLUSIONS:
      Chemotherapeutic agents can have adverse effects on information acquired
      pretreatment as well as new learning and memory and, despite some recovery,
      impairment is long lasting.

PMID- 22467681
TI  - Major involvement of mTOR in the PPARgamma-induced stimulation of adipose tissue
      lipid uptake and fat accretion.
AB  - Evidence points to a role of the mammalian target of rapamycin (mTOR) signaling
      pathway as a regulator of adiposity, yet its involvement as a mediator of the
      positive actions of peroxisome proliferator-activated receptor (PPAR)gamma
      agonism on lipemia, fat accretion, lipid uptake, and its major determinant
      lipoprotein lipase (LPL) remains to be elucidated. Herein we evaluated the plasma
      lipid profile, triacylglycerol (TAG) secretion rates, and adipose tissue LPL
      dependent lipid uptake, LPL expression/activity, and expression profile of other
      lipid metabolism genes in rats treated with the PPARgamma agonist rosiglitazone
      (15 mg/kg/day) in combination or not with the mTOR inhibitor rapamycin (2
      mg/kg/day) for 15 days. Rosiglitazone stimulated adipose tissue mTOR complex 1
      and AMPK and induced TAG-derived lipid uptake (136%), LPL mRNA/activity (2- to 6
      fold), and fat accretion in subcutaneous (but not visceral) white adipose tissue
      (WAT; 50%) and in brown adipose tissue (BAT; 266%). Chronic mTOR inhibition
      attenuated the upregulation of lipid uptake, LPL expression/activity, and fat
      accretion induced by PPARgamma activation in both subcutaneous WAT and BAT, which
      resulted in hyperlipidemia. In contrast, rapamycin did not affect most of the
      other WAT lipogenic genes upregulated by rosiglitazone. Together these findings
      demonstrate that mTOR is a major regulator of adipose tissue LPL-mediated lipid
      uptake and a critical mediator of the hypolipidemic and lipogenic actions of
      PPARgamma activation.

PMID- 22467682
TI  - Imatinib triggers mesenchymal-like conversion of CML cells associated with
      increased aggressiveness.
AB  - Chronic myelogenous leukemia (CML) is a cytogenetic disorder resulting from the
      expression of p210BCR-ABL. Imatinib, an inhibitor of BCR-ABL, has emerged as the
      leading compound to treat CML patients. Despite encouraging clinical results,
      resistance to imatinib represents a major drawback for therapy, as a substantial
      proportion of patients are refractory to this treatment. Recent publications have
      described the existence of a small cancer cell population with the potential to
      exhibit the phenotypic switch responsible for chemoresistance. To investigate the
      existence of such a chemoresistant cellular subpopulation in CML, we used a two
      step approach of pulse and continuous selection by imatinib in different CML cell
      lines that allowed the emergence of a subpopulation of adherent cells (IM-R Adh)
      displaying an epithelial-mesenchymal transition (EMT)-like phenotype.
      Overexpression of several EMT markers was observed in this CML subpopulation, as
      well as in CD34(+) CML primary cells from patients who responded poorly to
      imatinib treatment. In response to imatinib, this CD44(high)/CD24(low) IM-R Adh
      subpopulation exhibited increased adhesion, transmigration and invasion in vitro
      and in vivo through specific overexpression of the alphaVbeta3 receptor. FAK/Akt
      pathway activation following integrin beta3 (ITGbeta3) engagement mediated the
      migration and invasion of IM-R Adh cells, whereas persistent activation of ERK
      counteracted BCR-ABL inhibition by imatinib, promoting cell adhesion-mediated
      resistance.

PMID- 22467683
TI  - Coexpression network analysis in chronic hepatitis B and C hepatic lesions
      reveals distinct patterns of disease progression to hepatocellular carcinoma.
AB  - Chronic infections with the hepatitis B virus (HBV) and hepatitis C virus (HCV)
      are the major risks of hepatocellular carcinoma (HCC), and great efforts have
      been made towards the understanding of the different mechanisms that link the
      viral infection of hepatic lesions to HCC development. In this work, we developed
      a novel framework to identify distinct patterns of gene coexpression networks and
      inflammation-related modules from genome-scale microarray data upon viral
      infection, and further classified them into oncogenic and dysfunctional ones. The
      core of our framework lies in the comparative study on viral infection modules
      across different disease stages and disease types--the module preservation during
      disease progression is evaluated according to the change of network connectivity
      in different stages, while the similarity and difference in HBV and HCV are
      evaluated by comparing the overlap of gene compositions and functional
      annotations in HBV and HCV modules. In particular, we revealed two types of
      driving modules related to infection for carcinogenesis in HBV and HCV,
      respectively, i.e. pro-apoptosis modules that are oncogenic in HBV, and anti
      apoptosis and inflammation modules that are oncogenic in HCV, which are in
      concordance with the results of previous differential expression-based
      approaches. Moreover, we found that intracellular protein transmembrane
      transportation and the transmembrane receptor protein tyrosine kinase signaling
      pathway act as oncogenic factors in HBV-HCC. Our findings provide novel insights
      into viral hepatocarcinogenesis and disease progression, and also demonstrate the
      advantages of an integrative and comparative network analysis over the existing
      differential expression-based approach and virus-host interactome-based approach.

PMID- 22467684
TI  - Does neuroimaging have a role in assessing criminal culpability?

PMID- 22467685
TI  - A skeptic's guide to guidelines.

PMID- 22467686
TI  - Comorbid conditions.

PMID- 22467688
TI  - Root causes.

PMID- 22467690
TI  - Technology and abuse.

PMID- 22467692
TI  - Alert fatigue.

PMID- 22467694
TI  - The performance of conventional and fluorescence-based methods for occlusal
      caries detection: an in vivo study with histologic validation.
AB  - BACKGROUND: The authors conducted an in vivo study to determine clinical cutoffs
      for a laser fluorescence (LF) device, an LF pen and a fluorescence camera (FC),
      as well as to evaluate the clinical performance of these methods and conventional
      methods in detecting occlusal caries in permanent teeth by using the histologic
      gold standard for total validation of the sample. METHODS: One trained examiner
      assessed 105 occlusal surfaces by using the LF device, LF pen, FC, International
      Caries Detection and Assessment System (ICDAS) criteria and bitewing (BW)
      radiographic methods. After tooth extraction, the authors assessed the teeth
      histologically. They determined the optimal clinical cutoffs by means of receiver
      operating characteristic curve analysis. RESULTS: The specificities and
      sensitivities for enamel and dentin caries detection versus only dentin caries
      detection thresholds were 0.60 and 0.93 and 0.77 and 0.52 (ICDAS), 1.00 and 0.29
      and 0.97 and 0.44 (BW radiography), 1.00 and 0.85 and 0.77 and 0.81 (LF device),
      0.80 and 0.89 and 0.71 and 0.85 (LF pen) and 0.80 and 0.74 and 0.49 and 0.85
      (FC), respectively. The accuracy values were higher for ICDAS, the LF device and
      the LF pen than they were for BW radiography and the FC. CONCLUSIONS: The
      clinical cutoffs for sound teeth, enamel carious lesions and dentin carious
      lesions were, respectively, 0 through 4, 5 through 27 and 28 through 99 (LF
      device); 0 through 4, 5 through 32 and 33 through 99 (LF pen); and 0 through 1.2,
      1.3 and 1.4 through 5.0 (FC). The ICDAS, the LF device and the LF pen
      demonstrated good performance in helping detect occlusal caries in vivo. The
      ICDAS did not seem to perform as well at the D(3) threshold (histologic scores 3
      and 4) as at the D(1) threshold (histologic scores 1-4). BW radiography and the
      FC had the lowest performances in helping detect lesions at the D(1) and D(3)
      thresholds, respectively. CLINICAL IMPLICATIONS: Occlusal caries detection should
      be based primarily on visual inspection. Fluorescence-based methods may be used
      to provide a second opinion in clinical practice.

PMID- 22467695
TI  - Electromyography in diagnosing temporomandibular disorders.
AB  - BACKGROUND: Although electromyography (EMG) has been used extensively in
      dentistry to assess masticatory muscle impairments in several conditions,
      especially temporomandibular disorders (TMDs), many investigators have questioned
      its psychometric properties and accuracy in diagnosing TMD. TYPES OF STUDIES
      REVIEWED: The authors conducted a systematic review to analyze the literature
      critically and determine the accuracy of EMG in diagnosing TMDs. They conducted
      an electronic search of MEDLINE, Embase, all Evidence-Based Medicine Reviews,
      Allied and Complementary Medicine, Ovid HealthSTAR and SciVerse Scopus. The
      authors selected abstracts that fulfilled the inclusion criteria, retrieved the
      original articles, verified the inclusion criteria and hand searched the
      articles' references. They used a methodological tool (Quality Assessment of
      Diagnostic Accuracy Studies [QUADAS]) to evaluate the quality of the selected
      articles. RESULTS: The electronic database search resulted in a total of 130
      articles. The authors selected eight articles as potentially meeting eligibility
      for the review. Of these eight articles, only two fulfilled the study inclusion
      criteria, and the authors analyzed them. Investigators in both studies reported
      low sensitivity (values ranged from 0.15 to 0.40 in one study and a mean of 0.69
      in the second study). In addition, investigators in the two studies reported
      contradictory levels of specificity (values ranged from 0.95 to 0.98 in one
      study, and the mean value in the second study was 0.67). The likelihood ratios
      and predictive values were not helpful in diagnosing TMD by means of EMG. The
      quality of the two studies was poor on the basis of the QUADAS checklist.
      CLINICAL IMPLICATIONS: The authors of this systematic review found no evidence to
      support the use of EMG for the diagnosis of TMD.

PMID- 22467696
TI  - Coronectomy: a surgical option for impacted third molars in close proximity to
      the inferior alveolar nerve.
AB  - BACKGROUND: Damage to the inferior alveolar nerve (IAN) during the extraction of
      impacted mandibular third molars in close proximity to the mandibular canal is a
      postoperative complication that most frequently occurs in patients 40 years and
      older. METHODS: The authors evaluated the postoperative complications of 43
      coronectomies of impacted mandibular third molars in 37 patients (17 men and 20
      women, mean age [standard deviation] 31 [2] years). The authors used cone-beam
      computed tomographic images to determine that all of the teeth that underwent a
      coronectomy were in close proximity to the IAN. RESULTS: The authors did not
      observe neurological injuries to the IAN or to the lingual nerve. One patient
      complained of intermittent pain and, 10 months after undergoing the coronectomy,
      underwent a second operation for extraction of the root fragments. The root
      extraction did not result in any neurological deficits, because the root
      fragments had migrated from the mandibular canal. One case of alveolitis was
      reported that manifested 15 days after the coronectomy. CONCLUSIONS:
      Coronectomies are safer to perform than complete extractions in situations in
      which the third molar is in close proximity to the mandibular canal. Root
      migration generally is asymptomatic, but in a case in which the patient underwent
      a second operation, the risk of the patient's experiencing neurological injuries
      was reduced. CLINICAL IMPLICATIONS: Coronectomy appears to be a valid surgical
      alternative in patients 40 years and older who are at a higher risk of
      experiencing neurological deficits than are younger patients.

PMID- 22467697
TI  - Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double
      masked, placebo-controlled trial.
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS) is a painful condition of unknown
      etiology, affecting more than 2.5 billion people worldwide. Vitamin deficiencies
      have been implicated as a possible cause. METHODS: The authors conducted a single
      center, randomized, parallel-arm, double-masked, placebo-controlled study to
      examine the effect of daily multivitamin supplementation on the number and
      duration of RAS episodes. The authors randomly assigned 160 adults who had a
      validated history of at least three episodes of idiopathic minor RAS within the
      previous 12 months to one of two groups: the first group (n = 83) received a once
      daily multivitamin containing 100 percent of the U.S. reference daily intake
      (RDI) of essential vitamins, and the second group (n = 77) received once-daily
      placebo for up to 365 days. RESULTS: The results showed no significant difference
      in the mean number of new RAS episodes between the multivitamin (4.19 episodes)
      and placebo (4.60 episodes) arms during the study period (P = .69). The mean
      duration of new RAS episodes also was similar for the multivitamin (8.66 days)
      and placebo (8.99 days) arms (P = .60). Furthermore, the authors found no
      differences between the two arms with regard to mouth pain, normalcy of diet or
      compliance with the study medication regimen. CONCLUSION: Daily multivitamin
      supplementation, with the RDI of essential vitamins, did not result in a
      reduction in the number or duration of RAS episodes. CLINICAL IMPLICATIONS:
      Clinicians should not recommend multi-vitamin supplementation routinely as
      prophylaxis for RAS.

PMID- 22467698
TI  - Dentin caries activity in early occlusal lesions selected to receive operative
      treatment: findings from the Practitioners Engaged in Applied Research and
      Learning (PEARL) Network.
AB  - BACKGROUND: Members of the practice-based research network Practitioners Engaged
      in Applied Research and Learning (PEARL) Network investigated the dentin caries
      activity in early occlusal lesions and its relationship to patient age,
      preoperative tooth sensitivity and radiographic appearance, as well as its
      influence on preparation depth and volume. METHODS: PEARL Network practitioner
      investigators (P-Is) (n = 45), general dentists who were trained but whose
      methods were not calibrated, conducted a study regarding postoperative
      hypersensitivity in resin-based composite restorations. The P-Is enrolled as
      study participants 613 patients with occlusal carious lesions that, in the P-Is'
      clinical judgment, required restoration. The P-Is used baseline radiographs to
      assess the depth and extent of the lesions. Data for 671 restorations included
      baseline sensitivity; ranking of dentin caries activity on the opening of the
      enamel; radiographic visibility (n = 652); and measurements of preparation depth,
      width and length. RESULTS: P-Is found rapidly progressing dentin caries in 38.5
      percent (258 of 671) of lesions and slowly progressing (and potentially inactive
      dentin) caries in the remainder of the lesions. Rapidly progressing caries was
      not related to the participant's age or participant-reported preoperative
      hypersensitivity but was related to the lesion depth as seen radiographically (P
      < .001) and depth (P < .001) and volume (P < .001) of the preparation. Molars had
      slightly higher but not statistically significant levels of caries activity.
      CONCLUSION: Rapidly progressing dentin caries, while present in only 38.5 percent
      of lesions, was related to the lesion's radiographic appearance but not to the
      participant's age or the study tooth's pre-operative sensitivity. CLINICAL
      IMPLICATIONS: On the basis of the low level of rapidly progressing dentin caries
      in this study population and the fact that slowly progressing caries can be
      inactive or remineralizing, the authors advise sealing versus operative treatment
      of early or shallow occlusal lesions.

PMID- 22467699
TI  - A practitioner's guide to developing critical appraisal skills: translating
      research into clinical practice.
AB  - BACKGROUND AND OVERVIEW: To understand research and develop skills in adopting
      research findings, clinicians must overcome a series of challenges. First is
      determining exactly what constitutes evidence-based care. The amount of often
      contradictory research findings and "expert" opinion that is available can be
      overwhelming and should not always be taken as best evidence. Accessing the best
      evidence has its own set of difficulties. Then there is the final challenge of
      actually incorporating that best evidence into practice, as knowing what should
      be done rarely is enough to bring about an immediate change in what is done.
      However, there are means available to help overcome these barriers. CONCLUSIONS
      AND PRACTICE IMPLICATIONS: Critical summaries of systematic reviews, along with
      evidence-based treatment recommendations, have emerged as highly condensed,
      easily accessible vehicles for staying current with research findings. There also
      is emerging evidence of effective strategies for implementing research findings
      in practice, as well as organizations with which clinicians can engage to ensure
      that their patient care is based on the best scientific information available.

PMID- 22467700
TI  - Effectiveness of different treatment regimens for peri-implantitis.

PMID- 22467701
TI  - Dentist, artist, pioneer: orthodontic innovator Norman Kingsley and his Rembrandt
      portraits.
AB  - BACKGROUND AND OVERVIEW: Norman W. Kingsley (1829-1913) was one of the most
      inventive contributors to the early development of orthodontics and cleft palate
      therapy. Gifted not only in dentistry but also in art, he was a sculptor and
      painter of considerable renown in his day. The author reports the rediscovery of
      two Kingsley paintings--exacting copies of Rembrandt self-portraits. Kingsley
      created them by using pyrography, a rare and difficult wood-charring artistic
      technique that he helped perfect.

PMID- 22467702
TI  - Indirect restoration use: a changing paradigm.

PMID- 22467703
TI  - Managing a successful practice in the postrecession economy.

PMID- 22467704
TI  - Who is responsible ethically for patient care in a corporate dental practice in
      which i am an employee dentist?

PMID- 22467705
TI  - An evaluation of selected vinyl polysiloxane and vinyl polysiloxane-hybrid
      elastomeric impression materials.

PMID- 22467707
TI  - Global health and development: conceptualizing health between economic growth and
      environmental sustainability.
AB  - After World War II, health was firmly integrated into the discourse about
      national development. Transition theories portrayed health improvements as part
      of an overall development pattern based on economic growth as modeled by the
      recent history of industrialization in high-income countries. In the 1970s, an
      increasing awareness of the environmental degradation caused by industrialization
      challenged the conventional model of development. Gradually, it became clear that
      health improvements depended on poverty-reduction strategies including
      industrialization. Industrialization, in turn, risked aggravating environmental
      degradation with its negative effects on public health. Thus, public health in
      low-income countries threatened to suffer from lack of economic development as
      well as from the results of global economic development. Similarly, demands of
      developing countries risked being trapped between calls for global wealth
      redistribution, a political impossibility, and calls for unrestricted material
      development, which, in a world of finite land, water, air, energy, and resources,
      increasingly looked like a physical impossibility, too. Various international
      bodies, including the WHO, the Brundtland Commission, and the World Bank, tried
      to capture the problem and solution strategies in development theories. Broadly
      conceived, two models have emerged: a "localist model," which analyzes national
      health data and advocates growth policies with a strong focus on poverty
      reduction, and a "globalist" model, based on global health data, which calls for
      growth optimization, rather than maximization. Both models have focused on
      different types of health burdens and have received support from different
      institutions. In a nutshell, the health discourse epitomized a larger controversy
      regarding competing visions of development. 

PMID- 22467708
TI  - Spirometric definition of COPD: exercise in futility or factual debate?

PMID- 22467709
TI  - Letter to the editor: "The Edelman equation as it applies to acute and chronic
      hyponatremia".

PMID- 22467710
TI  - Is the socioeconomic gap in childhood exposure to secondhand smoke widening or
      narrowing?
AB  - OBJECTIVE: The social gradient in smoking contributes substantially to the health
      gap between the rich and poor. Passive smoking by children is associated with
      increased risk of more severe asthma, respiratory diseases and infections, middle
      ear disease and Sudden Infant Death Syndrome. This study examined trends in the
      social gradient of children's exposure to secondhand smoke in Australian
      households between 2001 and 2010. DESIGN: Series of cross-sectional national
      household surveys. RESULTS: Between 2001 and 2010, the proportion of Australian
      households containing a child aged under 15 years and a smoker declined by 22%.
      However, there was no change in the most disadvantaged households, with half of
      these households still containing at least one smoker in 2010. There was a social
      gradient in outdoor smoking in all survey years but the prevalence of outdoor
      only smoking increased in all socioeconomic groups by around 50% between 2001 and
      2010. The presence of a child aged 5 years or younger in the household increased
      the chances that smokers only smoked outdoors. CONCLUSIONS: Children's exposure
      to indoor smoking in households that contain a smoker is declining in all
      socioeconomic groups but the social class differentials in such exposure remain.
      The proportion of children who live with a smoker declined in all social groups
      except the most disadvantaged households, with half of these households still
      containing a smoker in 2010. More needs to be done to reduce secondhand smoke
      exposure of children in socially disadvantaged households.

PMID- 22467711
TI  - South Korea: 'KT&G Sangsang Univ.' employs education for marketing.

PMID- 22467712
TI  - Interactive effects of nocturnal transpiration and climate change on the root
      hydraulic redistribution and carbon and water budgets of southern United States
      pine plantations.
AB  - Deep root water uptake and hydraulic redistribution (HR) have been shown to play
      a major role in forest ecosystems during drought, but little is known about the
      impact of climate change, fertilization and soil characteristics on HR and its
      consequences on water and carbon fluxes. Using data from three mid-rotation
      loblolly pine plantations, and simulations with the process-based model MuSICA,
      this study indicated that HR can mitigate the effects of soil drying and had
      important implications for carbon uptake potential and net ecosystem exchange
      (NEE), especially when N fertilization is considered. At the coastal site (C),
      characterized by deep organic soil, HR increased dry season tree transpiration
      (T) by up to 40%, and such an increase affected NEE through major changes in
      gross primary productivity (GPP). Deep-rooted trees did not necessarily translate
      into a large volume of HR unless soil texture allowed large water potential
      gradients to occur, as was the case at the sandy site (S). At the Piedmont site
      (P) characterized by a shallow clay-loam soil, HR was low but not negligible,
      representing up to 10% of T. In the absence of HR, it was predicted that at the
      C, S and P sites, annual GPP would have been diminished by 19, 7 and 9%,
      respectively. Under future climate conditions HR was predicted to be reduced by
      up to 25% at the C site, reducing the resilience of trees to precipitation
      deficits. The effect of HR on T and GPP was predicted to diminish under future
      conditions by 12 and 6% at the C and P sites, respectively. Under future
      conditions, T was predicted to stay the same at the P site, but to be marginally
      reduced at the C site and slightly increased at the S site. Future conditions and
      N fertilization would decrease T by 25% at the C site, by 15% at the P site and
      by 8% at the S site. At the C and S sites, GPP was estimated to increase by 18%
      and by >70% under future conditions, respectively, with little effect of N
      fertilization. At the P site, future conditions would stimulate GPP by only 12%,
      but future conditions plus N fertilization would increase GPP by 24%. As a
      consequence, in all sites, water use efficiency was predicted to improve
      dramatically with future conditions. Modeling the effect of reduced annual
      precipitation indicated that limited water availability would decrease all carbon
      fluxes, including NEE and respiration. Our simulations highlight the interactive
      effects of nutrients and elevated CO(2), and showed that the effect of N
      fertilization would be greater under future climate conditions.

PMID- 22467716
TI  - Pure pancreatic-type acinar cell carcinoma of the stomach: a case report.
AB  - Acinar cell carcinoma is an uncommon carcinoma of the exocrine pancreas. On very
      rare occasions it has been reported in ectopic sites, sometimes with, but usually
      without contiguous heterotopic pancreatic tissue. Whilst mixed and composite
      glandular tumours have also been described, pure pancreatic-type acinar cell
      carcinomas arising in the stomach are very rare.

PMID- 22467717
TI  - Interferon-inducible transmembrane proteins of the innate immune response act as
      membrane organizers by influencing clathrin and v-ATPase localization and
      function.
AB  - The innate response interferon-inducible transmembrane (Ifitm) proteins have been
      characterized as influencing proliferation, signaling complexes and restricting
      virus infections. Treatment of cells lacking these proteins (IfitmDel) with IFN
      beta resulted in the loss of clathrin from membrane compartments and the
      inhibition of clathrin-mediated phagocytosis, suggesting a molecular interaction
      between clathrin and Ifitm proteins. The pH of endosomes of IfitmDel cells, with
      or without IFN activation, was neutralized, suggesting the function of the
      vacular ATPase proton pumps in such cells was compromised. Co-immunoprecipitation
      of Ifitm3 with Atp6v0b demonstrated a direct interaction between the Ifitm
      proteins and the v-ATPase. These data suggest that the Ifitm proteins help
      stabilize v-ATPase complexes in cellular membranes which, in turn, facilitates
      the appropriate subcellular localization of clathrin.

PMID- 22467718
TI  - Pentraxin-3 in COPD: innocent bystander or amplifier?

PMID- 22467719
TI  - Desmosine, a biomarker for COPD: old and in the way.

PMID- 22467720
TI  - Towards prognostic biomarkers in pulmonary arterial hypertension.

PMID- 22467721
TI  - Rational use of anti-tuberculosis drugs in the EU: better patient care and less
      drug resistance.

PMID- 22467722
TI  - Triple therapy in idiopathic pulmonary fibrosis: an alarming press release.

PMID- 22467724
TI  - Towards individualised medicine for airways disease: identifying clinical
      phenotype groups.

PMID- 22467725
TI  - Serum neurotrophin-3 and neurotrophin-4 levels are associated with asthma
      severity in children.

PMID- 22467723
TI  - European union standards for tuberculosis care.
AB  - The European Centre for Disease Prevention and Control (ECDC) and the European
      Respiratory Society (ERS) jointly developed European Union Standards for
      Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored
      standards for the diagnosis, treatment and prevention of tuberculosis (TB). The
      International Standards for TB Care (ISTC) were developed in the global context
      and are not always adapted to the EU setting and practices. The majority of EU
      countries have the resources and capacity to implement higher standards to
      further secure quality TB diagnosis, treatment and prevention. On this basis, the
      ESTC were developed as standards specifically tailored to the EU setting. A panel
      of 30 international experts, led by a writing group and the ERS and ECDC,
      identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV
      and comorbid conditions, and public health and prevention. The ISTCs formed the
      basis for the 21 standards, upon which additional EU adaptations and supplements
      were developed. These patient-centred standards are targeted to clinicians and
      public health workers, providing an easy-to-use resource, guiding through all
      required activities to ensure optimal diagnosis, treatment and prevention of TB.
      These will support EU health programmes to identify and develop optimal
      procedures for TB care, control and elimination.

PMID- 22467726
TI  - Value of s-ACE, BAL lymphocytosis, and CD4+/CD8+ and CD103+CD4+/CD4+ T-cell
      ratios in diagnosis of sarcoidosis.

PMID- 22467727
TI  - Surgical salvage following stereotactic body radiotherapy for early-stage NSCLC.

PMID- 22467728
TI  - Tracheobronchial amyloidosis: evidence for local B-cell clonal expansion.

PMID- 22467729
TI  - Curing HIV-associated pulmonary arterial hypertension.

PMID- 22467730
TI  - Home oxygen therapy during natural disasters: lessons from the great East Japan
      earthquake.

PMID- 22467731
TI  - Call for an international survey on therapeutic lavage for pulmonary alveolar
      proteinosis.

PMID- 22467732
TI  - Prescribing and guidelines: both must improve to combat antimicrobial resistance.

PMID- 22467733
TI  - Is sleep related to cancer in murine models of obstructive sleep disorder?

PMID- 22467734
TI  - Primary lung adenocarcinoma: characteristics by smoking habit and sex.

PMID- 22467735
TI  - Do we always need computed tomography to detect and treat parapneumonic pleural
      effusion?

PMID- 22467737
TI  - What the pulmonary specialist should know about the new inhalation therapies.

PMID- 22467740
TI  - Age at disease onset predicts likelihood and rapidity of growth failure among
      infants and young children with spinal muscular atrophy types 1 and 2.
AB  - Growth failure is nearly universal in spinal muscular atrophy type 1 and common
      in type 2, although acuity is often underappreciated at initial diagnosis. We
      reviewed 44 consecutive spinal muscular atrophy patients (28 type 1, 16 type 2)
      under 3 years at initial presentation. Growth failure was conventionally defined:
      weight below the fifth percentile or dropping 2 major percentiles over 6 months.
      Growth failure differed among subjects stratified by age at disease onset using
      the Kaplan-Meier method (P = 0.011). Median time to growth failure among subjects
      with onset between 0 to 3 months of age was 5 months; Only 1 of 22 avoided
      failure by 22 months of age. Median time to failure with disease onset between 4
      to 6 months was 15 months. Most late onset (> 6 months) subjects avoided growth
      failure. Early clinical symptoms predict feeding dysfunction and growth failure.
      Immediate, proactive nutritional intervention is indicated for patients with
      early symptom onset.

PMID- 22467741
TI  - Ethosuximide-induced conversion of typical childhood absence to Rolandic spikes.
AB  - Coexistence of 2 idiopathic epilepsy syndromes (ie, childhood absence and
      Rolandic epilepsy), as evidenced by electroencephalographic (EEG) findings with
      or without clinical features of the 2 conditions, is uncommon and remains
      controversial. Few case reports support this coexistence either as a continuum or
      drug-induced conversion, whereas a large sample case review did not find such co
      occurrence. The authors report a case of conversion of typical absence to
      Rolandic spikes after treatment with ethosuximide. An 11-year-old girl was
      diagnosed with typical childhood absence epilepsy at the age of 6 years with
      classic clinical and EEG features. She became seizure-free on ethosuximide but
      her follow-up EEGs consistently recorded right centrotemporal and centroparietal
      spikes without associated clinical seizures. This case may suggest simultaneous
      presence of these 2 common childhood idiopathic epilepsies either as a continuum
      or a drug-induced conversion.

PMID- 22467742
TI  - A gelatinous human tail with lipomyelocele: case report.
AB  - We report a female infant who presented with a tail appendage bearing a
      gelatinous tip and an associated lipomyelocele. Magnetic resonance images
      revealed the presence of spina bifida and a tract in continuity from the tail to
      the conus medullaris. The tail was surgically removed. A human tail may be
      associated with underlying spinal dysraphism. Magnetic resonance or computed
      tomographic imaging is required in such cases for complete evaluation. This is
      the first case report of gelatinous-tip human tail.

PMID- 22467743
TI  - Analysis of the conformation and function of the Plasmodium falciparum merozoite
      proteins MTRAP and PTRAMP.
AB  - Thrombospondin repeat (TSR)-like domains are structures involved with cell
      adhesion. Plasmodium falciparum proteins containing TSR domains play crucial
      roles in parasite development. In particular, the preerythrocytic P. falciparum
      circumsporozoite protein is involved in hepatocyte invasion. The importance of
      these domains in two other malaria proteins, the merozoite-specific
      thrombospondin-related anonymous protein (MTRAP) and the thrombospondin-related
      apical membrane protein (PTRAMP), were assessed using near-full-length
      recombinant proteins composed of the extracellular domains produced in
      Escherichia coli. MTRAP is thought to be released from invasive organelles
      identified as micronemes during merozoite invasion to mediate motility and host
      cell invasion through an interaction with aldolase, an actin binding protein
      involved in the moving junction. PTRAMP function remains unknown. In this study,
      the conformation of recombinant MTRAP (rMTRAP) appeared to be a highly extended
      protein (2 nm by 33 nm, width by length, respectively), whereas rPTRAMP had a
      less extended structure. Using an erythrocyte binding assay, rMTRAP but not
      rPTRAMP bound human erythrocytes; rMTRAP binding was mediated through the TSR
      domain. MTRAP- and in general PTRAMP-specific antibodies failed to inhibit P.
      falciparum development in vitro. Altogether, MTRAP is a highly extended
      bifunctional protein that binds to an erythrocyte receptor and the merozoite
      motor.

PMID- 22467744
TI  - Functional analysis of sequence motifs involved in the polyadenylation of
      Trichomonas vaginalis mRNAs.
AB  - Synthesis of functional mRNA in eukaryotes involves processing of precursor
      transcripts, including the addition of a poly(A) tail at the 3' end. A
      multiprotein complex recognizes a polyadenylation signal, generally the
      hexanucleotide AAUAAA in metazoans, to direct processing of the pre-mRNA. Based
      on sequence analysis of several cDNAs, we have previously suggested that the UAAA
      tetranucleotide (which may include the UAA translation stop codon) could be the
      polyadenylation signal in Trichomonas vaginalis, a parasitic protozoon that
      causes human trichomoniasis. This proposal is analyzed here with the aid of a
      transient-expression system of a reporter gene (cat flanked by T. vaginalis actin
      noncoding sequences). When cells were transfected with a plasmid bearing the
      original 3' untranslated region (UTR) sequence containing the UAAA motif, the
      resulting cat mRNA was polyadenylated similarly to the endogenous actin mRNA.
      Base changes in the UAAA sequence produced alterations to the polyadenylation
      site of the reporter mRNAs, while nucleotide substitutions at either side of UAAA
      did not. Furthermore, relocation of the UAAA motif redirected the processing and
      polyadenylation of the reporter mRNA. In addition, a pre-mRNA cleavage site for
      polyadenylation was defined. Interaction of T. vaginalis proteins with the UAAA
      motif was shown by electrophoretic mobility shift assays. Based on our findings,
      we provide evidence that in T. vaginalis the UAAA tetranucleotide has a role
      equivalent to that of the metazoan consensus AAUAAA polyadenylation signal.

PMID- 22467745
TI  - Crush recommendations: a step forward in disaster nephrology.

PMID- 22467746
TI  - Ongoing gaps in CKD and CVD care: re-evaluating strategies for knowledge
      dissemination.

PMID- 22467747
TI  - Volume overload as a mechanism for obstructive sleep apnea in CKD?

PMID- 22467748
TI  - Epidermal growth factor: a new therapeutic target in glomerular disease.
AB  - Glomerular kidney diseases are of major public health importance because of their
      strong impact on the quality of life of patients and of their costly management.
      A relatively neglected area of study is the local factors that influence
      development of glomerular demolition. The involvement of a glomerular factor has
      been now demonstrated in glomerulonephritis with cell proliferation such as
      crescentic rapidly progressive glomerulonephritis (RPGN). Various unrelated
      immune disorders promote RPGN, such as antibodies directed against the glomerular
      basement membrane, deposition of immune complexes or antibodies directed against
      neutrophils. Despite the heterogeneity of these causing diseases, RPGNs share
      similar histopathological features, which suggest involvement of common final
      pathways. De novo expression of heparin-binding epidermal growth factor-like
      growth factor (HB-EGF) in glomerular epithelial cells is found specifically in
      human glomerulonephritis with proliferation of these cells and dedifferentiation
      of podocytes. A receptor for HB-EGF, the EGF receptor (EGFR), is expressed by
      parietal epithelial cells and podocytes. Furthermore, in a mouse model of RPGN,
      HB-EGF deficiency or conditional targeting of the Egfr alleles in podocytes
      markedly alleviated RPGN, renal failure and death. This indicates that the HB
      EGF/EGFR pathway plays a pivotal role in RPGN and opens therapeutic perspectives
      as EGFR inhibitors are clinically available.

PMID- 22467749
TI  - Current status of transplantation and organ donation in the Balkans--could it be
      improved through the South-eastern Europe Health Network (SEEHN) initiative?
AB  - Organ donation and transplantation activity in the majority of Balkan countries
      (Albania, Bosnia and Herzegovina, Croatia, Macedonia, Moldova, Montenegro,
      Serbia, Romania and Bulgaria) are lagging far behind international averages.
      Inadequate financial resources, unclear regional data and lack of government
      infrastructure are some of the issues which should be recognized to draw
      attention and lead to problem-solving decisions. The Regional Health Development
      Centre (RHDC) Croatia, a technical body of the South-eastern Europe Health
      Network (SEEHN), was created in 2011 after Croatia's great success in the field
      over the last 10 years. The aim of the RHDC is to network the region and provide
      individualized country support to increase donation and transplantation activity
      in collaboration with professional societies (European Society of Organ
      Transplantation, European Transplant Coordinators Organization, The
      Transplantation Society and International Society of Organ Donation and
      Procurement). Such an improvement would in turn likely prevent transplant
      tourism. The regional data from 2010 show large discrepancies in donation and
      transplantation activities within geographically neighbouring countries. Thus,
      proposed actions to improve regional donation and transplantation rates include
      advancing living and deceased donation through regular public education, creating
      current and accurate waiting lists and increasing the number of educated
      transplant nephrologists and hospital coordinators. In addition to the effort
      from the professionals, government support with allocated funds per deceased
      donation, updated legislation and an established national coordinating body is
      ultimately recognized as essential for the successful donation and
      transplantation programmes. By continuous RHDC communication and support asked
      from the health authorities and motivated professionals from the SEEHN
      initiative, an increased number of deceased as well as living donor kidney
      transplantations in the future should be more realistic.

PMID- 22467750
TI  - Vitamin D and nephrology.

PMID- 22467751
TI  - Renal sympathetic nerve ablation for the treatment of difficult-to-control or
      refractory hypertension in a haemodialysis patient.
AB  - Haemodialysis patients show sympathetic hyperactivity. Hyperactivation of the
      sympathetic nervous system aggravates hypertension and it is related to left
      ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. We report
      the first use of renal sympathetic nerve ablation for correction of uncontrolled
      hypertension in an end-stage renal disease patient on maintenance dialysis. We
      observed a progressive and sustained reduction of systemic blood pressure. Our
      case demonstrates the safety, the feasibility and the efficacy of this procedure.
      These findings suggest, however, that further clinical trials are needed into
      renal nerve radiofrequency ablation therapy for the treatment of hypertension and
      for the improvement of cardiovascular prognosis in this high-risk patient group.

PMID- 22467753
TI  - Leadership in child health.

PMID- 22467752
TI  - Mechanical unloading reverses transverse tubule remodelling and normalizes local
      Ca(2+)-induced Ca(2+)release in a rodent model of heart failure.
AB  - AIMS: Ca(2+)-induced Ca(2+) release (CICR) is critical for contraction in
      cardiomyocytes. The transverse (t)-tubule system guarantees the proximity of the
      triggers for Ca(2+) release [L-type Ca(2+) channel, dihydropyridine receptors
      (DHPRs)] and the sarcoplasmic reticulum Ca(2+) release channels [ryanodine
      receptors (RyRs)]. Transverse tubule disruption occurs early in heart failure
      (HF). Clinical studies of left ventricular assist devices in HF indicate that
      mechanical unloading induces reverse remodelling. We hypothesize that unloading
      of failing hearts normalizes t-tubule structure and improves CICR. METHODS AND
      RESULTS: Heart failure was induced in Lewis rats by left coronary artery ligation
      for 12 weeks; sham-operated animals were used as controls. Failing hearts were
      mechanically unloaded for 4 weeks by heterotopic abdominal heart transplantation
      (HF-UN). HF reduced the t-tubule density measured by di-8-ANEPPS staining in
      isolated left ventricular myocytes, and this was reversed by unloading. The
      deterioration in the regularity of the t-tubule system in HF was also reversed in
      HF-UN. Scanning ion conductance microscopy showed the reappearance of normal
      surface striations in HF-UN. Electron microscopy revealed recovery of normal t
      tubule microarchitecture in HF-UN. L-type Ca(2+) current density, measured using
      whole-cell patch clamping, was reduced in HF but unaffected by unloading. The
      variance of the time-to-peak of the Ca(2+) transient, an index of CICR
      dyssynchrony, was increased in HF and normalized by unloading. The increased
      Ca(2+) spark frequency observed in HF was reduced in HF-UN. These results could
      be explained by the recoupling of orphaned RyRs in HF, as indicated by
      immunofluorescence. CONCLUSIONS: Our data show that mechanical unloading of the
      failing heart reverses the pathological remodelling of the t-tubule system and
      improves CICR.

PMID- 22467754
TI  - Left ventricular lead position for cardiac resynchronization: a comprehensive
      cinegraphic, echocardiographic, clinical, and survival analysis.
AB  - AIMS: We sought to determine the clinical and survival outcomes of cardiac
      resynchronization therapy (CRT) associated with left ventricular (LV) lead
      location. The lateral left ventricle has been considered the optimal LV lead
      location for CRT. METHODS AND RESULTS: Left ventricular lead cinegrams taken in
      30 degrees  right and left anterior oblique views were evaluated in 457
      recipients of CRT with a pacemaker or a defibrillator from 1 January 2002 to 31
      December 2008 in this retrospective study. Left ventricular lead placement was
      prioritized at implantation into posterolateral (PL), anterolateral (AL), middle
      cardiac, and anterointerventricular coronary veins. Using echocardiographic LV 16
      segment analysis, we grouped the leads as anterior, AL, PL, and posterior
      locations. New York Heart Association (NYHA) class and echocardiography were
      assessed before and after CRT. Clinical and survival outcomes after CRT were
      compared among the four LV lead locations.  Patient baseline demographic
      characteristics were similar among these four groups. Improvement in NYHA class
      was significantly greater in the AL (P= 0.04) and PL (P= 0.03) locations than in
      the anterior location. There was a tendency for greater improvement in LV
      ejection fraction among the AL (P= 0.11) and PL (P= 0.08) locations than the
      anterior location. Kaplan-Meier survival estimate at 4 years varied for location:
      AL, 72%; anterior, 48%; PL, 62%; and posterior, 72% (P= 0.003). CONCLUSION:
      Cardiac resynchronization therapy recipients are profiting from all lead
      positions. However, LV lead placed in the AL and PL positions is more
      preferential for achieving optimal CRT benefit than leads placed in the anterior
      position.

PMID- 22467755
TI  - A new world for the conquistadors?

PMID- 22467756
TI  - Commentaries on viewpoint: the curious case of anabolic resistance: old wives'
      tales or new fables?

PMID- 22467757
TI  - Last word on viewpoint: the curious case of anabolic resistance: old wives' tales
      or new fables?

PMID- 22467758
TI  - Effect of policy changes on cigarette sales: the case of Turkey.
AB  - BACKGROUND: In 1996, Turkey made tobacco control a health priority. The tobacco
      control effort was extended in July 2009 with the expansion of the smoke-free law
      to include all enclosed workplaces and public places and, in January 2010, with a
      20% increase in the Special Consumption Tax on Tobacco. METHODS: Sales data were
      averaged, by month, for the period January 2005 through June 2009 to establish an
      'expected' monthly sales pattern. This was the period when no new tobacco control
      measures were implemented. The overall monthly average was then calculated for
      the same period. The expected monthly sales pattern was then graphed against the
      overall monthly sales average to delineate a seasonal sales pattern that was used
      to evaluate the divergence of actual monthly sales from the 'expected' pattern.
      RESULTS: A distinct seasonal pattern was found with sales above average from May
      through August. Comparison of actual cigarette sales to the 'expected' monthly
      sales pattern following the implementation of the expanded smoke-free law in July
      resulted in a 5.2% decrease. Cigarettes sales decreased by 13.6% following the
      January 2010 Special Consumption Tax. Since the implementation of the expanded
      smoke-free law in July 2009 and the tax increase in January 2010, cigarette sales
      in Turkey decreased by 10.7%. CONCLUSION: The effect of recent Turkish tobacco
      control policies could contribute to a reduction in the number of premature
      deaths related to tobacco use. Evidence has shown that periodic tax increases and
      strong enforcement of all tobacco control policies are essential to further
      decrease tobacco consumption.

PMID- 22467759
TI  - Food restriction and refeeding induces changes in lipid pathways and fat
      deposition in the adipose and hepatic tissues in rats with diet-induced obesity.
AB  - The aim of this study was to determine the effects of successive cycles of a
      moderately restrictive diet and refeeding with a high-fat diet on the metabolism
      of the adipose and hepatic tissues of obese rats. Rats were assigned to the
      following groups: a chow diet; a high-fat diet; a moderate caloric restriction;
      or a moderate caloric restriction plus refeeding. Some animals in each group were
      given [1-(14)C]triolein intragastrically, while others received an
      intraperitoneal injection of 3 mCi (3)H(2)O. All animals were killed by
      decapitation. The retroperitoneal, visceral epididymal and omental white adipose
      tissues, brown adipose tissue, liver and blood were immediately removed. The
      lipid uptake from the diet, in vivo rate of lipogenesis, percentage of fat, lipid
      profile and leptin concentration were analysed. The high-fat diet promoted an
      increase in fatty liver (P <= 0.05), adiposity mass (P <= 0.05) and the plasma
      concentration of leptin (P <= 0.05) and a decreased lipid uptake in white adipose
      tissue depots (P <= 0.05) in relation to the chow diet. The moderate caloric
      restriction did not reverse the changes promoted by the high-fat diet but induced
      a small decrease in adiposity, which was reversed after refeeding, and the
      animals maintained a dyslipidaemic profile and high fat deposition in the liver.
      We can conclude that the high-fat diet and subsequent moderate caloric
      restriction plus refeeding increased the risks of developing visceral obesity,
      dyslipidaemia and non-alcoholic fatty liver disease, which suggests that this
      type of experimental protocol can be used to study mechanisms related to the
      metabolic syndrome.

PMID- 22467760
TI  - Anterograde and retrograde blood velocity profiles in the intact human
      cardiovascular system.
AB  - Current assessments of the effects of shear patterns on vascular function assume
      that a parabolic velocity profile is always present. Any substantial deviation in
      the profile away from this may result in misinterpretation of the importance that
      shear patterns have on vascular function. The present investigation tested the
      hypothesis that anterograde and retrograde blood flow would have a parabolic
      velocity profile at rest, during cold pressor test and exercise. Eight healthy
      subjects completed a cold pressor test and a graded knee-extension exercise test.
      Doppler ultrasound was used to determine time-averaged mean velocity (V(mean))
      and time-averaged peak velocity (V(peak)) for both anterograde and retrograde
      flow in the femoral artery (FA) and brachial artery (BA). The V(mean)/V(peak)
      ratio was used to interpret the shape of the blood velocity profile (parabolic,
      V(mean)/V(peak) = 0.5; plug-like, V(mean)/V(peak) = 1.0). At rest, BA and FA
      V(mean)/V(peak) ratios of anterograde and retrograde flow were not significantly
      different from 0.5. During cold pressor test, anterograde V(mean)/V(peak) in the
      BA (0.56 +/- 0.02) and FA (0.58 +/- 0.03) were significantly greater than 0.5.
      During peak exercise, the V(mean)/V(peak) ratio of anterograde flow in the FA
      (0.53 +/- 0.04) was not significantly different from 0.5. In all conditions, the
      retrograde V(mean)/V(peak) ratio was lower than anterograde. These data
      demonstrate that blood flow through two different conduit arteries during two
      different physiological stressors maintains a velocity profile that resembles a
      slightly blunted parabolic velocity profile.

PMID- 22467761
TI  - Actomyosin kinetics of pure fast and slow rat myosin isoforms studied by in vitro
      motility assay approach.
AB  - An in vitro motility assay approach was used to investigate the mechanisms of the
      functional differences between myosin isoforms, by studying the effect of MgATP
      and MgADP on actin sliding velocity (V(f)) of pure slow and fast rat skeletal
      myosin at different temperatures. The value of V(f) depended on [MgATP] according
      to Michaelis-Menten kinetics, with an apparent constant (K(m)) of 54.2, 64.4 and
      200 MUm for the fast isoform and 18.6, 36.5 and 45.5 MUM for the slow isoform at
      20, 25 and 35 degrees C, respectively. The presence of 2 mM MgADP decreased V(f)
      and yielded an inhibition constant (K(i)) of 377, 463 and 533 MUM for the fast
      isoform at 20, 25 and 35 degrees C, respectively, and 120 and 355 MUM for the
      slow isoform at 25 and 35 degrees C, respectively. The analysis of K(m) and K(i)
      suggested that slow and fast isoforms differ in the kinetics limiting V(f).
      Moreover, the higher sensitivity of the fast myosin isoform to a drop in [MgATP]
      is consistent with the higher fatigability of fast fibres than slow fibres. From
      the Michaelis-Menten relation in the absence of MgADP, we calculated the rate of
      actomyosin dissociation by MgATP (k(+ATP)) and the rate of MgADP release (k(
      ADP)). We found values of k(+ATP) of 4.8 * 10(6), 6.5 * 10(6) and 6.6 * 10(6) M(
      1) s(-1) for the fast isoform and 3.3 * 10(6), 2.9 * 10(6) and 6.7 * 10(6) M(-1)
      s(-1) for the slow isoform and values of k(-ADP) of 263, 420 and 1320 s(-1) for
      the fast isoform and 62, 107 and 306 s(-1) for the slow isoform at 20, 25 and 35
      degrees C, respectively. The results suggest that k(-ADP) could be the major
      determinant of functional differences between the fast and slow myosin isoforms
      at physiological temperatures.

PMID- 22467762
TI  - An antagonist of human protease activated receptor-2 attenuates PAR2 signaling,
      macrophage activation, mast cell degranulation, and collagen-induced arthritis in
      rats.
AB  - Multiple serine proteases exert proinflammatory actions by signaling through
      protease-activated receptor-2 (PAR2) on the cell surface. Although inhibitors of
      individual proteases are anti-inflammatory, we sought to discover whether the
      first potent antagonist of their common target PAR2 might be beneficial in
      treating chronic arthritis-like inflammatory disease. Using a fluorescence assay,
      a novel compound, GB88, was shown to antagonize PAR2-induced intracellular Ca(2+)
      release in human monocyte-derived macrophages, being 1000 times more potent than
      a control compound, ENMD-1068 (IC(50) 1.6 +/- 0.5 MUM vs. 1.2 +/- 0.4 mM,
      respectively). In Wistar rats, GB88 was orally bioavailable (F=55%, T(max) 4 h,
      C(max) 1.7 MUM, 10 mg/kg). GB88 inhibited the acute paw edema induced in Wistar
      rats by intraplantar lambda-carrageenan or PAR2 agonists 2-furoyl-LIGRLO-NH(2) or
      mast cell beta-tryptase, without inhibiting proteolytic activity of tryptase in
      vitro. In the chronic collagen-induced model of arthritis in rats, GB88 (10
      mg/kg) was disease modifying and ameliorated pathological and histopathological
      changes (edema, pannus formation, synovial hyperplasia, collagen degradation,
      macrophage invasion, mast cell degranulation) compared to untreated arthritic
      controls. The results suggest that an orally active PAR2 antagonist is effective
      in treating chronic arthritis in rats through inhibiting macrophage infiltration,
      mast cell degranulation, and beta-tryptase-PAR2 signaling in joint inflammation.

PMID- 22467777
TI  - CT-guided cryoablation for palliation of secondary trigeminal neuralgia from head
      and neck malignancy.
AB  - BACKGROUND: Facial pain is a common presentation secondary to tumoral invasion,
      rendering an individual unable to perform basic activities such as eating and
      talking. Cryotherapy may be appropriate in patients seeking immediate pain relief
      for trigeminal neuralgia (TN) near the end of life with its minimal invasiveness
      and procedural morbidity. While cryosurgery has been effectively demonstrated in
      the treatment of primary TN, this study is unique as it is the first documented
      use of CT guidance and treatment of secondary TN using percutaneous cryoablation.
      AIM: To perform and report experience with CT-guided percutaneous cryoablation, a
      palliative treatment for TN secondary to recurrent invasive head and neck
      carcinoma, in patients previously treated with chemotherapy, radiotherapy and/or
      surgery with the goal of improving functional status and quality of life.
      METHODS: Palliative cryoablation procedures performed under CT guidance on
      recurrent head and neck malignancy between September 2010 and June 2011 were
      retrospectively analyzed. The procedure was performed under general anesthesia or
      conscious sedation. For each patient, 1-2 cryoprobes were placed in the tumor and
      two or four freeze-thaw cycles were performed. Patients were evaluated for facial
      pain relief immediately after treatment by telephone follow-up. RESULTS: Three
      patients underwent treatment for three masses using CT-guided percutaneous
      cryoablation. On imaging, technical success was achieved in all cases with
      hypodense ice formation encompassing symptomatic lesions on the CT scan. No
      procedural complications were encountered with post-procedure pain relief and
      reduction in required pain medication noted in all patients. One patient had 1
      month of pain relief before the symptoms returned. CONCLUSION: CT-guided
      percutaneous cryoablation is an efficient minimally invasive method for the
      palliative treatment of TN secondary to recurrent invasive head and neck
      carcinoma as a result of direct tumoral invasion of the extracranial divisions of
      the trigeminal nerve. Patients meeting the therapeutic criteria of individuals
      treated for musculoskeletal metastatic lesions may benefit from this treatment.
      The results suggest it may not currently be a curative technique as one patient's
      symptoms returned, but it could prove useful as an adjunct to current palliative
      therapies with minimal invasiveness and procedural morbidity, especially in
      patients seeking pain palliation, improved functional status and improved quality
      of life near the end of life.

PMID- 22467763
TI  - Recommendation for the management of crush victims in mass disasters.
AB  - "Recommendations for the management of crush victims in mass disasters" aims to
      assist medics, paramedics and rescue team members who provide care during
      disasters. Development of the recommendations followed an explicit process of
      literature review and, also internet and face-to-face discussions. The chapters
      cover medical and logistic measures, to be taken both at the disaster field and
      in the hospitals, to cope with the problems created by a catastrophe.
      Recommendations were based on retrospective analyses and case reports on past
      disasters, and also expert judgment or opinion. Since there are no randomized
      controlled trials, no GRADE approach was used to develop the recommendations, and
      no strengths of recommendations or levels of evidence are provided.

PMID- 22467778
TI  - The Fagerstrom Test for Nicotine Dependence as a predictor of smoking abstinence:
      a pooled analysis of varenicline clinical trial data.
AB  - INTRODUCTION: We explored the relationship between the Fagerstrom Test for
      Nicotine Dependence (FTND) and smoking abstinence rates in 10 randomized, double
      blind placebo-controlled Phase 2-4 varenicline studies. METHODS: Participants
      were adult smokers (>=10 cigarettes/day) who were motivated to quit. Efficacy end
      points included continuous abstinence rate (CAR) for weeks 9-24 analyzed, by
      baseline FTND and Heaviness of Smoking Index (HSI) scores, and treatment. Data
      were analyzed using logistic regression models. RESULTS: Overall, 2,763
      varenicline (M [SD] FTND score: 5.6 [2.2]) and 2,229 placebo subjects (5.5 [2.1])
      were included in the analysis. An increase of one unit in baseline FTND or HSI
      score decreased the odds of abstinence at Week 24 by 11% (odds ratio [OR] 0.89,
      95% CI 0.86-0.92, p < .0001) and 18% (OR 0.82, 95% CI 0.79-0.87, p < .0001),
      respectively. Treatment had a significant impact on CAR 9-24: odds of abstinence
      were increased threefold for varenicline versus placebo (OR 3.3, 95% CI 2.8-3.8,
      p < .0001). There was no interaction between treatment and FTND (p = .98) or HSI
      score (p = .97) for CAR 9-24. The HSI score predicted abstinence outcome as
      effectively as the FTND score. CONCLUSION: Abstinence rates decreased with
      increasing dependence scores. There was no interaction between treatment and
      baseline FTND or HSI score, suggesting that they have no effect on the efficacy
      of varenicline versus placebo. These results also suggest that the HSI may be as
      effective at predicting smoking cessation outcome as the whole FTND
      questionnaire.

PMID- 22467779
TI  - Environment-mediated accumulation of diacyl lipoproteins over their triacyl
      counterparts in Staphylococcus aureus.
AB  - Bacterial lipoproteins are believed to exist in only one specific lipid-modified
      structure, such as the diacyl form or the triacyl form, in each bacterium. In the
      case of Staphylococcus aureus, recent extensive matrix-assisted laser desorption
      ionization-time of flight (MALDI-TOF) mass spectrometry analysis revealed that S.
      aureus lipoproteins exist in the alpha-aminoacylated triacyl form. Here, we
      discovered conditions that induce the accumulation of diacyl lipoproteins that
      lack alpha-aminoacylation in S. aureus. The accumulation of diacyl lipoproteins
      required a combination of conditions, including acidic pH and a post-logarithmic
      growth phase. High temperatures and high salt concentrations additively
      accelerated the accumulation of the diacyl lipoprotein form. Following a post
      logarithmic-growth phase where S. aureus MW2 cells were grown at pH 6, SitC
      lipoprotein was found almost exclusively in its diacyl structure rather than in
      its triacyl structure. This is the first report showing that the environment
      mediates lipid-modified structural alterations of bacterial lipoproteins.

PMID- 22467780
TI  - Stringent response regulation of biofilm formation in Vibrio cholerae.
AB  - Biofilm formation is a key factor in Vibrio cholerae environmental survival and
      host colonization. Production of biofilm enables V. cholerae to survive and
      persist in aquatic environments and aids in the passage through the gastric acid
      barrier to allow access to the small intestine. The genes involved in biofilm
      formation are regulated by the transcriptional activators vpsR and vpsT, which
      are in turn transcriptionally regulated by a number of environmental signals. In
      this study, the role of the stringent response in biofilm formation was examined.
      V. cholerae mutants deficient in stringent response had a reduced ability to form
      biofilms, although they were not completely deficient in biofilm formation. There
      are three (p)ppGpp synthases in V. cholerae: RelA, SpoT, and RelV. All three
      synthases were necessary for vpsR transcription, with RelV showing the strongest
      effect. RelA was the only synthase that was necessary for vpsT expression.
      Stringent response regulation of vpsR and vpsT was shown to partially occur
      through rpoS. Biofilm formation in V. cholerae is controlled by a complex
      regulatory apparatus, with negative regulators of biofilm gene expression, such
      as quorum sensing, and positive regulators of biofilm genes, including stringent
      response, interacting to ensure that biofilm formation is coordinated with the
      environment.

PMID- 22467781
TI  - Prevalence of avian-pathogenic Escherichia coli strain O1 genomic islands among
      extraintestinal and commensal E. coli isolates.
AB  - Escherichia coli strains that cause disease outside the intestine are known as
      extraintestinal pathogenic E. coli (ExPEC) and include pathogens of humans and
      animals. Previously, the genome of avian-pathogenic E. coli (APEC) O1:K1:H7
      strain O1, from ST95, was sequenced and compared to those of several other E.
      coli strains, identifying 43 genomic islands. Here, the genomic islands of APEC
      O1 were compared to those of other sequenced E. coli strains, and the
      distribution of 81 genes belonging to 12 APEC O1 genomic islands among 828 human
      and avian ExPEC and commensal E. coli isolates was determined. Multiple islands
      were highly prevalent among isolates belonging to the O1 and O18 serogroups
      within phylogenetic group B2, which are implicated in human neonatal meningitis.
      Because of the extensive genomic similarities between APEC O1 and other human
      ExPEC strains belonging to the ST95 phylogenetic lineage, its ability to cause
      disease in a rat model of sepsis and meningitis was assessed. Unlike other ST95
      lineage strains, APEC O1 was unable to cause bacteremia or meningitis in the
      neonatal rat model and was significantly less virulent than uropathogenic E. coli
      (UPEC) CFT073 in a mouse sepsis model, despite carrying multiple neonatal
      meningitis E. coli (NMEC) virulence factors and belonging to the ST95
      phylogenetic lineage. These results suggest that host adaptation or genome
      modifications have occurred either in APEC O1 or in highly virulent ExPEC
      isolates, resulting in differences in pathogenicity. Overall, the genomic islands
      examined provide targets for further discrimination of the different ExPEC
      subpathotypes, serogroups, phylogenetic types, and sequence types.

PMID- 22467782
TI  - N-acylation of lipoproteins: not when sour.

PMID- 22467783
TI  - Allele-dependent differences in quorum-sensing dynamics result in variant
      expression of virulence genes in Staphylococcus aureus.
AB  - Agr is an autoinducing, quorum-sensing system that functions in many Gram
      positive species and is best characterized in the pathogen Staphylococcus aureus,
      in which it is a global regulator of virulence gene expression. Allelic
      variations in the agr genes have resulted in the emergence of four quorum-sensing
      specificity groups in S. aureus, which correlate with different strain
      pathotypes. The basis for these predilections is unclear but is hypothesized to
      involve the phenomenon of quorum-sensing interference between strains of
      different agr groups, which may drive S. aureus strain isolation and divergence.
      Whether properties intrinsic to each agr allele directly influence virulence
      phenotypes within S. aureus is unknown. In this study, we examined group-specific
      differences in agr autoinduction and virulence gene regulation by utilizing
      congenic strains, each harboring a unique S. aureus agr allele, enabling a
      dissection of agr locus-dependent versus genotype-dependent effects on quorum
      sensing dynamics and virulence factor production. Employing a reporter fusion to
      the principal agr promoter, P3, we observed allele-dependent differences in the
      timing and magnitude of agr activation. These differences were mediated by
      polymorphisms within the agrBDCA genes and translated to significant variations
      in the expression of a key transcriptional regulator, Rot, and of several
      important exoproteins and surface factors involved in pathogenesis. This work
      uncovers the contribution of divergent quorum-sensing alleles to variant
      expression of virulence determinants within a bacterial species.

PMID- 22467784
TI  - Stress response and virulence functions of the Acinetobacter baumannii NfuA Fe-S
      scaffold protein.
AB  - To successfully establish an infection, Acinetobacter baumannii must overcome the
      iron starvation and oxidative stress imposed by the human host. Although previous
      studies have shown that ATCC 19606(T) cells acquire iron via the acinetobactin
      mediated siderophore system, little is known about intracellular iron metabolism
      and its relation to oxidative stress in this pathogen. Screening of an insertion
      library resulted in the isolation of the ATCC 19606(T) derivative 1644, which was
      unable to grow in iron-chelated media. Rescue cloning and DNA sequencing showed
      that the insertion inactivated a gene coding for an NfuA Fe-S cluster protein
      ortholog, without any effect on the expression of the acinetobactin system. The
      nfuA mutant was also more sensitive to hydrogen peroxide and cumene hydroperoxide
      than the parental strain. The iron chelation- and oxidative-stress-deficient
      responses of this mutant were corrected when complemented with either the ATCC
      19606(T) parental allele or the Escherichia coli MG1655 nfuA ortholog.
      Furthermore, electron paramagnetic resonance (EPR) and inductively coupled plasma
      atomic emission spectroscopy (ICP-AES) analyses showed that the ATCC 19606(T)
      NfuA ortholog has iron-binding properties compatible with the formation of [Fe-S]
      cluster protein. Ex vivo and in vivo assays using human epithelial cells and
      Galleria mellonella, respectively, showed that NfuA is critical for bacterial
      growth independent of their capacity to acquire iron or the presence of excess of
      free iron. Taken together, these observations indicate that the A. baumannii NfuA
      ortholog plays a role in intracellular iron utilization and protection from
      oxidative-stress responses that this pathogen could encounter during the
      infection of the human host.

PMID- 22467785
TI  - The structure of Mlc titration factor A (MtfA/YeeI) reveals a prototypical zinc
      metallopeptidase related to anthrax lethal factor.
AB  - MtfA of Escherichia coli (formerly YeeI) was previously identified as a regulator
      of the phosphoenolpyruvate (PEP)-dependent:glucose phosphotransferase system.
      MtfA homolog proteins are highly conserved, especially among beta- and
      gammaproteobacteria. We determined the crystal structures of the full-length MtfA
      apoenzyme from Klebsiella pneumoniae and its complex with zinc (holoenzyme) at
      2.2 and 1.95 A, respectively. MtfA contains a conserved
      H(149)E(150)XXH(153)+E(212)+Y(205) metallopeptidase motif. The presence of zinc
      in the active site induces significant conformational changes in the region
      around Tyr205 compared to the conformation of the apoenzyme. Additionally, the
      zinc-bound MtfA structure is in a self-inhibitory conformation where a region
      that was disordered in the unliganded structure is now observed in the active
      site and a nonproductive state of the enzyme is formed. MtfA is related to the
      catalytic domain of the anthrax lethal factor and the Mop protein involved in the
      virulence of Vibrio cholerae, with conservation in both overall structure and in
      the residues around the active site. These results clearly provide support for
      MtfA as a prototypical zinc metallopeptidase (gluzincin clan).

PMID- 22467786
TI  - Analysis of the CtrA pathway in Magnetospirillum reveals an ancestral role in
      motility in alphaproteobacteria.
AB  - Developmental events across the prokaryotic life cycle are highly regulated at
      the transcriptional and posttranslational levels. Key elements of a few
      regulatory networks are conserved among phylogenetic groups of bacteria, although
      the features controlled by these conserved systems are as diverse as the
      organisms encoding them. In this work, we probed the role of the CtrA regulatory
      network, conserved throughout the Alphaproteobacteria, in the magnetotactic
      bacterium Magnetospirillum magneticum strain AMB-1, which possesses unique
      intracellular organization and compartmentalization. While we have shown that
      CtrA in AMB-1 is not essential for viability, it is required for motility, and
      its putative phosphorylation state dictates the ability of CtrA to activate the
      flagellar biosynthesis gene cascade. Gene expression analysis of strains
      expressing active and inactive CtrA alleles points to the composition of the
      extended CtrA regulon, including both direct and indirect targets. These results,
      combined with a bioinformatic study of the AMB-1 genome, enabled the prediction
      of an AMB-1-specific CtrA binding site. Further, phylogenetic studies comparing
      CtrA sequences from alphaproteobacteria in which the role of CtrA has been
      experimentally examined reveal an ancestral role of CtrA in the regulation of
      motility and suggest that its essential functions in other alphaproteobacteria
      were acquired subsequently.

PMID- 22467787
TI  - Important role for Mycobacterium tuberculosis UvrD1 in pathogenesis and
      persistence apart from its function in nucleotide excision repair.
AB  - Mycobacterium tuberculosis survives and replicates in macrophages, where it is
      exposed to reactive oxygen and nitrogen species that damage DNA. In this study,
      we investigated the roles of UvrA and UvrD1, thought to be parts of the
      nucleotide excision repair pathway of M. tuberculosis. Strains in which uvrD1 was
      inactivated either alone or in conjunction with uvrA were constructed.
      Inactivation of uvrD1 resulted in a small colony phenotype, although growth in
      liquid culture was not significantly affected. The sensitivity of the mutant
      strains to UV irradiation and to mitomycin C highlighted the importance of the
      targeted genes for nucleotide excision repair. The mutant strains all exhibited
      heightened susceptibility to representatives of reactive oxygen intermediates
      (ROI) and reactive nitrogen intermediates (RNI). The uvrD1 and the uvrA uvrD1
      mutants showed decreased intracellular multiplication following infection of
      macrophages. Most importantly, the uvrA uvrD1 mutant was markedly attenuated
      following infection of mice by either the aerosol or the intravenous route.

PMID- 22467788
TI  - The PhoP/PhoQ system and its role in Serratia marcescens pathogenesis.
AB  - Serratia marcescens is able to invade, persist, and multiply inside nonphagocytic
      cells, residing in nonacidic, nondegradative, autophagosome-like vacuoles. In
      this work, we have examined the physiological role of the PhoP/PhoQ system and
      its function in the control of critical virulence phenotypes in S. marcescens. We
      have demonstrated the involvement of the PhoP/PhoQ system in the adaptation of
      this bacterium to growth on scarce environmental Mg(2+), at acidic pH, and in the
      presence of polymyxin B. We have also shown that these environmental conditions
      constitute signals that activate the PhoP/PhoQ system. We have found that the two
      S. marcescens mgtE orthologs present a conserved PhoP-binding motif and
      demonstrated that mgtE1 expression is PhoP dependent, reinforcing the importance
      of PhoP control in magnesium homeostasis. Finally, we have demonstrated that phoP
      expression is activated intracellularly and that a phoP mutant strain is
      defective in survival inside epithelial cells. We have shown that the Serratia
      PhoP/PhoQ system is involved in prevention of the delivery to degradative/acidic
      compartments.

PMID- 22467789
TI  - Characterization of the two-component monooxygenase system AlnT/AlnH reveals
      early timing of quinone formation in alnumycin biosynthesis.
AB  - Alnumycin A is an aromatic polyketide with a strong resemblance to related
      benzoisochromanequinone (BIQ) antibiotics, such as the model antibiotic
      actinorhodin. One intriguing difference between these metabolites is that the
      positions of the benzene and quinone rings are reversed in alnumycin A in
      comparison to the BIQ polyketides. In this paper we demonstrate that inactivation
      of either the monooxygenase alnT gene or the flavin reductase alnH gene results
      in the accumulation of a novel nonquinoid metabolite, thalnumycin A (ThA), in the
      culture medium. Additionally, two other previously characterized metabolites,
      K1115 A and 1,6-dihydroxy-8-propylanthraquinone (DHPA), were identified, which
      had oxidized into quinones putatively nonenzymatically at the incorrect position
      in the central ring. None of the compounds isolated contained correctly formed
      pyran rings, which suggests that on the alnumycin pathway quinone biosynthesis
      occurs prior to third ring cyclization. The regiochemistry of the two-component
      monooxygenase system AlnT/AlnH was finally confirmed in vitro by using ThA, FMN,
      and NADH in enzymatic synthesis, where the reaction product, thalnumycin B (ThB),
      was verified to contain the expected p-hydroquinone structure in the lateral
      ring.

PMID- 22467790
TI  - Transcription activation by NtcA in the absence of consensus NtcA-binding sites
      in an anabaena heterocyst differentiation gene promoter.
AB  - Heterocyst differentiation is orchestrated by the N control transcriptional
      regulator NtcA and the differentiation-specific factor HetR. In Anabaena sp.
      strain PCC 7120, the devBCA operon is expressed from two different promoters
      activated upon N stepdown. The distal devB promoter (transcription start point
      [TSP] located at position -704) represents a canonical class II NtcA-activated
      promoter, including a consensus NtcA-binding site centered 39.5 nucleotides
      upstream from the TSP. Transcription activation from a second TSP (-454) requires
      NtcA and is impaired in hetR mutants. In a wild-type background, three different
      DNA fragments, including both or each individual promoter, directed gfp
      expression localized mainly to proheterocysts and heterocysts. Expression was
      undetectable in an ntcA background and, for the fragment including the proximal
      promoter alone, also in a hetR background. In spite of the absence of consensus
      NtcA-binding sequences between the two TSPs, NtcA was shown to interact with this
      DNA region, and NtcA and its effector, 2-oxoglutarate, were necessary and
      sufficient for in vitro transcription from the -454 TSP. No HetR binding to the
      DNA or in vitro transcription from the proximal devB TSP promoted by HetR alone
      were detected. However, a moderate positive effect of HetR on NtcA binding to the
      DNA between the two devB TSPs was observed. The proximal devB promoter appears to
      represent a suboptimal NtcA-activated promoter for which HetR may act as a
      coactivator, with the physiological effect of restricting gene activation to
      conditions of prevalence of high NtcA and HetR levels, such as those taking place
      during heterocyst differentiation.

PMID- 22467791
TI  - Lacosamide in refractory mixed pediatric epilepsy: a prospective add-on study.
AB  - Lacosamide is a new antiepileptic drug that is currently approved by the US Food
      and Drug Administration (FDA) for adults 17 years or older for partial-onset
      seizures. The authors reviewed 21 pediatric patients (<17 years) with various
      seizure types who were started on oral lacosamide as part of a prospective add-on
      study as adjunctive therapy for refractory epilepsy. Five patients were excluded
      due to less than 3 months of meaningful follow-up. Maintenance dosages used
      ranged from 2.4 to 19.4 mg/kg/d. Eight of 16 (50%) patients had greater than 50%
      reduction in seizure frequency with adjunctive lacosamide therapy. Eight (50%)
      patients had generalized epilepsy including 4 with Lennox-Gastaut syndrome.
      Lacosamide was effective therapy for most seizure types but was particularly
      effective for partial-onset seizures. Lacosamide was effective in treating 5 of 8
      (62.5%) localization-related epilepsies but only 2 of 8 (25%) generalized
      epilepsies, both Lennox-Gastaut syndrome patients with greater than 90% seizure
      reduction. None of these very refractory patients remained seizure free.

PMID- 22467792
TI  - Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and migraine.

PMID- 22467793
TI  - Body mass index of children with attention-deficit/hyperactivity disorder.

PMID- 22467795
TI  - We thank Dr Eva Hnizdo and Professor Edward L Petsonk for their highly
      appreciated comments on our publication in Occupational Environmental Medicine.

PMID- 22467796
TI  - Comparison of exposure estimates in the Finnish job-exposure matrix FINJEM with a
      JEM derived from expert assessments performed in Montreal.
AB  - CONTEXT: Retrospective exposure assessment in population-based case-control
      studies poses a major challenge due to the wide range of occupations and
      industries involved. The FINJEM is a generic job-exposure matrix (JEM) developed
      in Finland, which represents a potentially cost-effective exposure assessment
      tool. While FINJEM has been used in several studies outside Finland, little is
      known of its applicability in other countries. METHODS: We compared prevalence
      and intensity of exposure in FINJEM with a JEM developed from expert assessments
      of occupational histories obtained in a population-based case-control study in
      Montreal. Agreement for prevalence of exposure was measured by weighted kappa
      coefficients between prevalence categories. Agreement for exposure intensity was
      measured by Spearman correlation coefficients between cells with non-null
      exposure. RESULTS: The comparison involved 27 chemicals, the time period 1945
      1995 and included 4743 jobs initially assessed by the Montreal experts. 4293
      combinations of agent, occupational title and period were available for
      comparison of prevalence. Agent-specific prevalence was consistently higher in
      the Montreal JEM (median difference 1.7%). Agent-specific kappa values between
      prevalence categories varied from 0.89 (welding fumes) to 0.07 (flour dust). The
      comparison of exposure levels involved 14 agents and 198 cells with non-null
      exposure in both sources. Agent-specific Spearman correlation varied from 0.89
      (flour dust) to -0.35 (benzo(a)pyrene). CONCLUSION: Our observations suggest that
      information concerning several agents (eg, metals, welding fumes) can be
      successfully transported from Finland to Canada and probably other countries.
      However, for other agents, there was considerable disagreement, and hence,
      transportability of FINJEM cannot be assumed by default.

PMID- 22467797
TI  - Prevalence of intestinal parasites in private-household cats in Japan.
AB  - The present study is the first national investigation of intestinal parasites in
      private-household cats in Japan. A total of 942 faecal samples were collected
      from private-household cats. Giardia species was assessed using an enzyme-linked
      immunosorbent assay kit and other intestinal parasites were identified
      microscopically. The overall prevalence of intestinal parasites was 10.1%; two
      protozoan parasites (Giardia species and Cystoisospora species) and five
      helminths (Toxocara cati, Toxascaris leonina, Ancylostoma tubaeforme, Taenia
      species and Spirometra erinacei) were detected. The total prevalence of
      intestinal parasite infection was significantly higher in cats aged <= 6 months
      old than in cats older than 6 months because of a significantly higher prevalence
      of Cystoisospora species and T cati. The total infection prevalence was higher
      among outdoor cats as a result of the significantly higher prevalence of T cati
      and S erinacei. Sex and faecal condition were not related to intestinal parasite
      infections. Regional differences were observed in Cystoisospora species and A
      tubaeforme.

PMID- 22467799
TI  - From microbe to microbiota: considering microbial community composition in
      infections and airway diseases.

PMID- 22467798
TI  - Histidine kinase activity of the ethylene receptor ETR1 facilitates the ethylene
      response in Arabidopsis.
AB  - In Arabidopsis (Arabidopsis thaliana), ethylene is perceived by a receptor family
      consisting of five members. Subfamily 1 members ETHYLENE RESPONSE1 (ETR1) and
      ETHYLENE RESPONSE SENSOR1 (ERS1) have histidine kinase activity, unlike the
      subfamily 2 members ETR2, ERS2, and ETHYLENE INSENSITIVE4 (EIN4), which lack
      amino acid residues critical for this enzymatic activity. To resolve the role of
      histidine kinase activity in signaling by the receptors, we transformed an etr1
      9;ers1-3 double mutant with wild-type and kinase-inactive versions of the
      receptor ETR1. Both wild-type and kinase-inactive ETR1 rescue the constitutive
      ethylene-response phenotype of etr1-9;ers1-3, restoring normal growth to the
      mutant in air. However, the lines carrying kinase-inactive ETR1 exhibit reduced
      sensitivity to ethylene based on several growth response assays. Microarray and
      real-time polymerase chain reaction analyses of gene expression support a role
      for histidine kinase activity in eliciting the ethylene response. In addition,
      protein levels of the Raf-like kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1), which
      physically associates with the ethylene receptor ETR1, are less responsive to
      ethylene in lines containing kinase-inactive ETR1. These data indicate that the
      histidine kinase activity of ETR1 is not required for but plays a modulating role
      in the regulation of ethylene responses. Models for how enzymatic and
      nonenzymatic regulation may facilitate signaling from the ethylene receptors are
      discussed.

PMID- 22467800
TI  - YKL-40, a chitinase-like protein at the intersection of inflammation and
      remodeling.

PMID- 22467801
TI  - Fetal ultrasound: shedding light or casting shadows on the fetal origins of
      airway disease.

PMID- 22467802
TI  - Is the doctor in? Views on the deployment of intensivists from both sides of the
      Atlantic.

PMID- 22467803
TI  - Secondary prevention of idiopathic pulmonary fibrosis: catching the horse still
      in the barn.

PMID- 22467804
TI  - Extracorporeal membrane oxygenation as "bridge" to lung transplantation: what
      remains in order to make it standard of care?

PMID- 22467805
TI  - A heavy heart.

PMID- 22467806
TI  - Vasoactive intestinal peptide in pulmonary arterial hypertension.

PMID- 22467807
TI  - Interferon-gamma release assays and the risk of developing active tuberculosis.

PMID- 22467808
TI  - Burnout or built in?

PMID- 22467809
TI  - Measuring metabolomics in acute lung injury: choosing the correct compartment?

PMID- 22467811
TI  - Disaster planning should take account of welfare, says FAWC.

PMID- 22467810
TI  - Diagnostic methylene blue test for stent covered tracheoesophageal fistula.

PMID- 22467812
TI  - Decline in human salmonellosis cases continues.

PMID- 22467813
TI  - Antimicrobial resistance in zoonotic bacteria.

PMID- 22467814
TI  - New consortium on worm control.

PMID- 22467815
TI  - Samples needed for a new sheep scab test in Scotland.

PMID- 22467816
TI  - Equine vet restored to the Register.

PMID- 22467817
TI  - Application for restoration dismissed.

PMID- 22467818
TI  - Last post-Chernobyl sheep controls to be removed.

PMID- 22467819
TI  - Netherlands rabies case highlights importance of following pet travel rules.

PMID- 22467820
TI  - A ticking clock for tickborne disease?

PMID- 22467822
TI  - Investigating epilepsy in dogs.

PMID- 22467823
TI  - Update on cattle health schemes in the UK.

PMID- 22467824
TI  - Disbudding goats.

PMID- 22467825
TI  - Disease associated with immature paramphistome infection in sheep.

PMID- 22467826
TI  - Joining the BVA's online community.

PMID- 22467827
TI  - Reasons for voting in RCVS Council elections.

PMID- 22467828
TI  - Structural characterization of mRNA-tRNA translocation intermediates.
AB  - Cryo-EM analysis of a wild-type Escherichia coli pretranslocational sample has
      revealed the presence of previously unseen intermediate substates of the
      bacterial ribosome during the first phase of translocation, characterized by
      intermediate intersubunit rotations, L1 stalk positions, and tRNA configurations.
      Furthermore, we describe the domain rearrangements in quantitative terms, which
      has allowed us to characterize the processivity and coordination of the
      conformational reorganization of the ribosome, along with the associated changes
      in tRNA ribosome-binding configuration. The results are consistent with the view
      of the ribosome as a molecular machine employing Brownian motion to reach a
      functionally productive state via a series of substates with incremental changes
      in conformation.

PMID- 22467829
TI  - Robust full-length hepatitis C virus genotype 2a and 2b infectious cultures using
      mutations identified by a systematic approach applicable to patient strains.
AB  - Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases
      worldwide, but treatment options are limited. Basic HCV research required for
      vaccine and drug development has been hampered by inability to culture patient
      isolates, and to date only the JFH1 (genotype 2a) recombinant replicates
      spontaneously in hepatoma cells and releases infectious virus. A JFH1 chimera
      with the 5' end through NS2 from another genotype 2a strain, J6, had enhanced
      infectivity. However, the full-length J6 clone (J6CF), which we previously found
      to be fully functional in vivo, was replication incompetent in vitro. Through a
      systematic approach of culturing J6 with minimal JFH1 sequences, we identified
      three mutations in NS3, NS4A, and NS5B that permitted full-length J6 propagation
      and adaptation with infectivity titers comparable to JFH1-based systems. The most
      efficient recombinant, J6cc, had six adaptive mutations and did not accumulate
      additional changes following viral passage. We demonstrated that HCV NS3/NS4A
      protease-, NS5A- and NS5B polymerase-directed drugs respectively inhibited full
      length J6 infection dose dependently. Importantly, the three J6-derived mutations
      enabled culture adaptation of the genetically divergent isolate J8 (genotype 2b),
      which differed from the J6 nucleotide sequence by 24%. The most efficient
      recombinant, J8cc, had nine adaptive mutations and was genetically stable after
      viral passage. The availability of these robust JFH1-independent genotype 2a and
      2b culture systems represents an important advance, and the approach used might
      permit culture development of other isolates, with implications for improved
      individualized treatments of HCV patients and for development of broadly
      efficient vaccines.

PMID- 22467830
TI  - Simple models of human brain functional networks.
AB  - Human brain functional networks are embedded in anatomical space and have
      topological properties--small-worldness, modularity, fat-tailed degree
      distributions--that are comparable to many other complex networks. Although a
      sophisticated set of measures is available to describe the topology of brain
      networks, the selection pressures that drive their formation remain largely
      unknown. Here we consider generative models for the probability of a functional
      connection (an edge) between two cortical regions (nodes) separated by some
      Euclidean distance in anatomical space. In particular, we propose a model in
      which the embedded topology of brain networks emerges from two competing factors:
      a distance penalty based on the cost of maintaining long-range connections; and a
      topological term that favors links between regions sharing similar input. We show
      that, together, these two biologically plausible factors are sufficient to
      capture an impressive range of topological properties of functional brain
      networks. Model parameters estimated in one set of functional MRI (fMRI) data on
      normal volunteers provided a good fit to networks estimated in a second
      independent sample of fMRI data. Furthermore, slightly detuned model parameters
      also generated a reasonable simulation of the abnormal properties of brain
      functional networks in people with schizophrenia. We therefore anticipate that
      many aspects of brain network organization, in health and disease, may be
      parsimoniously explained by an economical clustering rule for the probability of
      functional connectivity between different brain areas.

PMID- 22467832
TI  - Creating evidence-based research in adapted physical activity.
AB  - Professional practice guided by the best research evidence is a usually referred
      to as evidence-based practice. The aim of the present paper is to describe five
      fundamental beliefs of adapted physical activity practices that should be
      considered in an 8-step research model to create evidence-based research in
      adapted physical activity. The five beliefs are individualization, critical
      thinking, self-determination, program effectiveness, and multifactor complexity.
      The research model includes conceptualize the problem, conduct research on the
      process of the problem, conceptualize and specify the intervention, evaluate
      intervention outcomes, evaluate intervention processes, determine person-by
      treatment interactions, determine context-dependent limitations, and investigate
      factors related to intervention adoption maintenance. The eight steps are
      explained with reference to two research programs that used a randomized control
      group design.

PMID- 22467831
TI  - Patterns and plasticity in RNA-protein interactions enable recruitment of
      multiple proteins through a single site.
AB  - mRNA control hinges on the specificity and affinity of proteins for their RNA
      binding sites. Regulatory proteins must bind their own sites and reject even
      closely related noncognate sites. In the PUF [Pumilio and fem-3 binding factor
      (FBF)] family of RNA binding proteins, individual proteins discriminate
      differences in the length and sequence of binding sites, allowing each PUF to
      bind a distinct battery of mRNAs. Here, we show that despite these differences,
      the pattern of RNA interactions is conserved among PUF proteins: the two ends of
      the PUF protein make critical contacts with the two ends of the RNA sites.
      Despite this conserved "two-handed" pattern of recognition, the RNA sequence is
      flexible. Among the binding sites of yeast Puf4p, RNA sequence dictates the
      pattern in which RNA bases are flipped away from the binding surface of the
      protein. Small differences in RNA sequence allow new modes of control, recruiting
      Puf5p in addition to Puf4p to a single site. This embedded information adds a new
      layer of biological meaning to the connections between RNA targets and PUF
      proteins.

PMID- 22467833
TI  - The experience of choice in physical activity contexts for adults with mobility
      impairments.
AB  - This exploratory study described the experiences of choice in physical activity
      contexts for adults with mobility impairments. The experiences of 3 female and 2
      males with mobility impairments between 18 and 23 years of age were described
      using the interpretive phenomenological methods of individual interviews, written
      stories, and field notes. Thematic analysis revealed three themes: (a)
      interpreting the setting described participants' interpretation of the
      environment, person, and task when making movement choices; (b) alternative
      selection described how participants actively engaged in analyzing alternatives
      and choosing among them; and (c) implications of choices made described
      participants' evaluations of good and bad choices and what was learned. Evidence
      of effective choice making among adults with physical impairments suggests the
      potential efficacy of ecological task analysis as a pedagogical tool in physical
      activity contexts.

PMID- 22467834
TI  - Effect of stimulant medication use by children with ADHD on heart rate and
      perceived exertion.
AB  - The effect of stimulant medication use by children with attention
      deficit/hyperactivity disorder (ADHD) on the rating of perceived exertion (RPE)
      heart rate (HR) relationship was examined. Children with ADHD (n=20; 11.3+/-1.8
      yrs) and children without ADHD (n=25; 11.2+/-2.1 yrs) were studied. Children with
      ADHD were examined while on their usual dose of medication on the day of study.
      HR and RPE, using the OMNI RPE scale, were assessed during a graded exercise to
      peak voluntary effort. The RPE-HR relationship was determined individually and
      the intercept and slope responses were compared between groups. The intercept was
      132.4+/-19.5 bpm for children with ADHD and 120.6+/-15.7 bpm for children without
      ADHD. The slope was 7.3+/-1.9 bpm/RPE for the children with ADHD and 8.1+/-1.6
      bpm/ RPE for the children without ADHD. For the group with ADHD the intercept and
      slope values fell outside of the 95% CI observed in the control group. The
      altered relationship between RPE and HR with stimulant medication use in children
      with ADHD has practical implications with respect to the use of HR and RPE to
      monitor exercise intensity.

PMID- 22467835
TI  - Psychiatric symptoms in children with gross motor problems.
AB  - Children with psychiatric disorders often demonstrate gross motor problems. This
      study investigates if the reverse also holds true by assessing psychiatric
      symptoms present in children with gross motor problems. Emotional, behavioral,
      and autism spectrum disorders (ASD), as well as psychosocial problems, were
      assessed in a sample of 40 children with gross motor problems from an elementary
      school population (aged 7 through 12 years). Sixty-five percent of the sample met
      the criteria for psychiatric classification. Anxiety disorders were found most
      often (45%), followed by ASD (25%) and attention deficit hyperactivity disorders
      (15%). Internalizing (51%) and social problems (41%) were prominent, as was
      "stereotyped behavior" (92%) and "resistance to changes" (92%). Self-perceived
      incompetence was restricted to domains that were indeed impaired (i.e., the
      athletic and social domains). The results suggest that children with gross motor
      problems are strongly at risk for psychiatric problems including anxiety,
      internalization, and ASD.

PMID- 22467836
TI  - Prediction of energy expenditure from wrist accelerometry in people with and
      without Down syndrome.
AB  - This study examined the relationship between energy expenditure and wrist
      accelerometer output during walking in persons with and without Down syndrome
      (DS). Energy expenditure in metabolic equivalent units (METs) and activity-count
      rate were respectively measured with portable spirometry and a uniaxial wrist
      accelerometer in 17 persons with DS (age: 24.7+/-6.9 years; 9 women) and 21
      persons without DS (age: 26.3+/-5.2 years; 12 women) during six over-ground
      walking trials. Combined groups regression showed that the relationship between
      METs and activity-count rate differed between groups (p<.001). Separate models
      for each group included activity-count rate and squared activity-count rate as
      significant predictors of METs (p<=.005). Prediction of METs appeared accurate
      based on Bland-Altman plots and the lack of between-group difference in mean
      absolute prediction error (DS: 17.07%; Non-DS: 18.74%). Although persons with DS
      show altered METs to activity-count rate relationship during walking, prediction
      of their energy expenditure from wrist accelerometry appears feasible.

PMID- 22467837
TI  - Anaphylaxis: current state of knowledge for the modern physician.
AB  - Anaphylaxis is a severe, potentially fatal, hypersensitivity reaction of rapid
      onset. It may trigger life-threatening cardiopulmonary compromise, often with
      skin and mucosal changes such as urticaria and angioedema. The prevalence of
      anaphylaxis is increasing and the number of cases of fatal anaphylaxis appears to
      be rising. Food, insect stings, and drugs are the most common triggers. Novel
      triggers are increasingly seen and include delayed anaphylaxis to red meat, food
      dependent exercise-induced reactions and anaphylaxis to monoclonal antibodies.
      Anaphylaxis is usually IgE mediated, but other mechanisms also play a role for
      example direct mast cells activation. Differential diagnosis is discussed
      including asthma, syncope and shock; excessive endogenous histamine, food related
      syndromes, and some rare diagnoses. Intramuscular epinephrine is first line
      treatment. The role of other drugs is reviewed. Timed and serial serum tryptase
      measurements help to confirm the diagnosis. Long-term management is necessary to
      minimise the risk of recurrence and includes identification of the trigger(s),
      management of risk factors, education on avoidance and a formalised treatment
      plan with an epinephrine auto-injector if appropriate. Every patient who has
      experienced anaphylaxis should be referred to an allergy clinic for appropriate
      management. This is endorsed by many national guidelines (eg, UK NICE).
      Anaphylaxis is often misdiagnosed or miscoded as, for example, asthma or food
      allergy. Most doctors will encounter a patient with anaphylaxis in their career
      and should to be familiar with the clinical features, management and mechanisms
      of this potentially fatal condition.

PMID- 22467838
TI  - Imaging in children presenting with acute neurological deficit: paediatric stroke
      mimics.
AB  - Stroke mimics refer to conditions manifesting with neurologic deficits without
      underlying cerebrovascular diseases. Major causes in the paediatric population
      under this category include infections, inflammation, demyelination, neoplasm,
      drug related, phacomatosis, and miscellaneous disorders. These conditions and
      their respective imaging findings are briefly discussed here.

PMID- 22467839
TI  - Late-life bipolar disorder: advances in treatment, conceptualization, and
      research methodology.

PMID- 22467840
TI  - Acute bipolar I affective episode presentation across life span.
AB  - OBJECTIVES: There is a paucity of evidence on bipolar I acute symptoms'
      presentation in the elderly individuals compared to younger patients. The current
      literature provides little, and at times conflicting, information on age-related
      bipolar disorder (BD) symptom presentation. This article aims to compare symptom
      profile by age group among patients with bipolar I in an acute affective episode
      as evaluated in outpatient settings. METHODS: The current analyses include all
      Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)
      participants with a lifetime diagnosis of bipolar I disorder. We compared the
      presence and severity of acute mood elevation (mania and hypomania) and acute
      depression symptoms between younger (20-59 years old) and older individuals
      (older than or equal to 60 years). RESULTS: With the exception of
      distractibility, all acute depression symptoms presented with comparable
      frequency and severity between younger and older individuals. No statistical
      significance was found regarding the presence of psychotic symptoms between the 2
      groups, with symptoms reported by 11.2% of younger versus 9.4% older individuals,
      chi(2) (1, N = 1541) = 0.03, P = .74. No significant effects were found for mood
      elevation severity between the 2 age groups. Psychotic symptoms were reported in
      12.7% versus 15.2%, chi(2) (1, N = 658) = 0.07, P = .65, and irritability in
      97.7% versus 97.8%, chi(2) (1, N = 651) = 0.00, P = 1.00, in the younger and
      older group, respectively. CONCLUSION: We found no statistically significant
      association between age and symptoms presentation of acute depression and mood
      elevation among patients with BD I. Acute BD I affective states present with
      similar profile and severity in old and young patients.

PMID- 22467841
TI  - The risk factors for elderly patients with bipolar disorder having cerebral
      infarction.
AB  - OBJECTIVE: Patients with bipolar disorder are at high risk of developing strokes
      in the older life. Silent cerebral infarctions (SCIs) could be common in the
      elderly patients with bipolar disorder, but only small sample size reports are
      available. The purpose of this study was to assess the proportion of SCIs and
      determine the risk factors for cerebral infarction in elderly patients with
      bipolar disorder. METHODS: We recruited 43 patients with bipolar disorder over
      the age of 60 to undergo whole-brain magnetic resonance imaging (MRI). We divided
      them into 2 groups depending on whether infarction was present, and compared the
      potential variables of these 2 groups. RESULTS: There were 28 elderly patients
      with bipolar disorder (65.1%) having MRI-proven cerebral infarction. The SCIs
      were detected in 59.5% (N = 22) of 37 patients without a history of stroke,
      including 61.3% of 13 patients with late-onset age (>50 years) and 46.7% of 30
      patients with typical-onset age (<50 years). Logistic regression revealed that
      comorbidity with metabolic diseases (95% confidence interval [CI] for odds ratio
      [OR] = 1.24-40.59) was most strongly associated with cerebral infarction. The
      leukocyte counts (95% CI for OR = 1.10-3.93) and fasting blood sugar (95% CI for
      OR = 1.00-1.07) during the most recent acute psychiatric admission may be
      substituted as the risk factors. CONCLUSIONS: Cerebral infarctions tend to be
      neglected in more than half of the elderly patients with bipolar disorder,
      regardless of their age at onset. Metabolic abnormality and systemic inflammation
      may be the risk factors.

PMID- 22467842
TI  - Medical and psychiatric comorbidities among elderly individuals with bipolar
      disorder: a literature review.
AB  - INTRODUCTION: The common comorbid conditions that accompany late-life bipolar
      disorder (BD) have not been well studied. This is a literature review on
      psychiatric and medical comorbidities among elderly individuals with BD. METHODS:
      A focused literature review searched PubMed. Inclusion criteria were original
      research reports, in English, until June 2009, specifically focused on medical
      and psychiatric comorbidities in BD individuals over the age of 50. RESULTS: A
      limited number of studies were identified. Most involved small samples (n < 100).
      Metabolic syndrome, respiratory and cardiovascular conditions, and endocrine
      abnormalities are common, with patients having an average of 3 to 4 medical
      comorbid conditions. Approximately 4.5% to 19% of elderly individuals with BD
      have dementia. Rates of psychiatric comorbidity appear lower than in younger BD
      populations, with the most common concurrent psychiatric illnesses being anxiety
      and substance use disorders. Rates of comorbid medical conditions appear similar
      to rates among geriatric patients without BD. CONCLUSIONS: Elderly individuals
      with BD are burdened by multiple concomitant medical disorders. In contrast to
      the elevated rates of medical comorbidity, rates of psychiatric comorbidity
      appear lower in elderly individuals with BD than in younger populations with BD.
      Greater awareness of concurrent medical conditions might help inform coordinated
      care that considers both mental and physical health among geriatric patients with
      BD.

PMID- 22467843
TI  - A patient with bipolar disorder and antiphospholipid syndrome.
AB  - Antiphospholipidsyndrome (APS) is an autoimmune disorder which causes a hyper
      coagulable state characterized by recurrent thrombosis. It has a diverse range of
      central nervous system manifestations. We describe a case of a 61 year old man
      with bipolar disorder and APS, and we compare this to a previously reported case.
      Additionally, we reviewed literature regarding APS-related markers and the
      relationship of APS to other psychiatric and neurologic illnesses. We discuss
      possible mechanisms for an association between APS and bipolar disorder. We
      encourage clinicians to be aware of this possible relationship and have proposed
      research strategies.

PMID- 22467844
TI  - Mortality risk with the use of atypical antipsychotics in later-life bipolar
      disorder.
AB  - INTRODUCTION: In recent years, concerns about the use of antipsychotic
      medications in dementia have grown. There is limited data on mortality risk of
      atypical antipsychotics for other psychiatric disorders of later life such as
      bipolar disorder. METHODS: Data were derived from the national Department of
      Veterans Affairs registries for older patients with bipolar disorder (>=65 years)
      with a new start of an atypical antipsychotic (risperidone, olanzapine, or
      quetiapine) or valproic acid and derivatives during fiscal years 2001-2008. Six
      month mortality rates were compared for individual drug groups. RESULTS: The
      sample included 4717 patients. The risperidone cohort had the highest mortality
      rate (11.8 per 100 person-years) with the quetiapine and valproic acid cohorts
      having the lowest (5.3 and 4.6 per 100 person-years, respectively). Various
      methods to adjust for baseline differences including propensity models showed
      similar patterns. CONCLUSIONS: Among older patients with bipolar disorder, there
      may be differences in mortality risks among individual antipsychotic agents.

PMID- 22467845
TI  - Correlates of treatment response in depressed older adults with bipolar disorder.
AB  - AIMS: To identify baseline clinical factors associated with acute treatment
      response in depressed older adults with bipolar disorder (BD) receiving
      lamotrigine. METHODS: Secondary analysis of a multisite, 12-week, open-label,
      uncontrolled study of add-on lamotrigine in 57 adults 60 years and older with BD
      I or II depression. Measures included the Montgomery Asberg Depression Rating
      Scale (MADRS) and Young Mania Rating Scale (YMRS). Cardiometabolic risk was
      measured with total serum cholesterol and the Cumulative Illness Rating Scale
      Geriatric (CIRS-G) item #13 (endocrine/metabolic burden). Neurocognitive
      (executive) function was evaluated using the Trail Making Test. RESULTS: Greater
      reduction in MADRS from baseline was associated with higher baseline
      cardiometabolic burden at 6 and 9 weeks and lower YMRS scores at 9 weeks. At 12
      weeks, improvement in the MADRS from baseline was no longer significantly related
      to baseline cardiometabolic burden or YMRS scores. A longitudinal mixed model of
      MADRS scores corroborated these findings with a significant finding of time-by
      baseline cholesterol level interaction. In a subset of participants, better
      baseline executive function was related to greater improvement in the MADRS at 9
      weeks but not at 6 or 12 weeks. Among all participants, higher baseline YMRS
      scores were related to greater likelihood of dropout. CONCLUSIONS: Lamotrigine
      appears to work best in depressed elderly patients with BD who have high
      cardiometabolic risk and low level of mania. Agents like lamotrigine that act
      primarily on neuroprogressive pathways involving oxidative stress, neurotrophins,
      and inflammation may be particularly effective in individuals with BD who have
      significant cardiometabolic burden because of their effects on shared
      vulnerability factors in BD and medical illness.

PMID- 22467846
TI  - Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar
      depression.
AB  - INTRODUCTION: Despite the prevalence, associated comorbidities, and functional
      consequences of bipolar depression (BPD), underlying disease mechanisms remain
      unclear. Published studies of individuals with bipolar disorder implicate
      abnormalities in cellular energy metabolism. This study tests the hypotheses that
      the forward rate constant (k(for)) of creatine kinase (CK) is altered in older
      adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that
      enhance mitochondrial function, increases k(for) in elderly individuals with BPD
      treated with CoQ10 compared with untreated age- and sex-matched controls.
      METHODS: Ten older adults (ages 55 and above) with Diagnostic and Statistical
      Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current
      episode depressed and 8 older controls underwent two 4 Tesla (31)Phosphorus
      magnetic resonance spectroscopy ((31)PMRS) scans 8 weeks apart using a
      magnetization transfer (MT) acquisition scheme to calculate k(for). The BPD group
      was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2
      weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale
      (MADRS) was used to measure depression symptom severity. Baseline k(for) and
      changes in k(for) were compared between individuals with BPD and controls, not
      receiving CoQ. Clinical ratings were compared across time and associated with
      k(for) changes using repeated measures linear regression. RESULTS: The k(for) of
      CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean
      (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02),
      Wilcoxon rank sum exact P = .40). The k(for) for both CoQ10-treated BPD and
      controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon
      signed rank exact P = .01), with no significant difference in 8-week changes
      between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) =
      0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis,
      depression severity decreased with CoQ10 treatment in the group with BPD (F (3,7)
      = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t (9) = 
      2.40, P = .04) and 4 (t (9) = -3.80, P = .004). CONCLUSIONS: This study employing
      the novel MRS technique of MT did not demonstrate significance between group
      differences in the k(for) of CK but did observe a trend that would require
      confirmation in a larger study. An exploratory analysis suggested a reduction in
      depression symptom severity during treatment with high-dose CoEnzyme Q10 for
      older adults with BPD. Further studies exploring alterations of high-energy
      phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a
      randomized controlled trial are both warranted.

PMID- 22467847
TI  - The effects of lithium on renal function in older adults--a systematic review.
AB  - Chronic renal failure (CRF) and nephrogenic diabetes insipidus (NDI) are
      potential consequences of chronic lithium use, while acute renal failure (ARF)
      has been described in lithium intoxication. We performed a systematic review of
      all studies pertaining to the effects of lithium on the kidney in older adults.
      The ARF incidence was 1.5% per person-year and concurrent loop diuretic and
      angiotensin-converting enzyme inhibitor use with lithium increased the risk. The
      CRF prevalence estimates varied from 1.2% to 34%, with risk factors including
      age, previous lithium intoxication, polyuria, previously impaired renal function,
      and decreased maximal urine osmolality. The prevalence of NDI varied widely from
      1.8%  to 85%. Risk factors included lithium duration, dose, level, slow-release
      formulation, and clinical nonresponse. Except for amiloride use in NDI, there is
      little evidence for treatment of other lithium-induced adverse renal effects.
      Currently, there is no compelling evidence to suggest that lithium should be
      avoided in elderly patients for fear of renal side effects.

PMID- 22467848
TI  - Characteristics associated with inpatient versus outpatient status in older
      adults with bipolar disorder.
AB  - OBJECTIVES: This is an exploratory analysis of ambulatory and inpatient services
      utilization by older persons with type I bipolar disorder experiencing elevated
      mood. The association between type of treatment setting and the person's
      characteristics is explored within a framework that focuses upon predisposing,
      enhancing, and need characteristics. METHOD: Baseline assessments were conducted
      with the first 51 inpatients and 49 outpatients 60 years of age and older,
      meeting criteria for type I bipolar disorder, manic, hypomanic, or mixed episode
      enrolled in the geriatric bipolar disorder study (GERI-BD) study. We compared
      participants recruited from inpatient versus outpatient settings in regard to the
      patients' predisposing, enabling, and need characteristics. RESULTS: Being
      treated in an inpatient rather than an outpatient setting was associated with the
      predisposing characteristic of being non-Hispanic caucasian (odds ratio [OR]:
      0.1; P = .005) and past history of treatment with first-generation antipsychotics
      (OR: 6.5; P < .001), and the need characteristic reflected in having psychotic
      symptoms present in the current episode (OR: 126.08; P < .001). CONCLUSION:
      Ethnicity, past pharmacologic treatment, and current symptom severity are closely
      associated with treatment in inpatient settings. Clinicians and researchers
      should investigate whether closer monitoring of persons with well-validated
      predisposing and need characteristics can lead to their being treated in less
      costly but equally effective ambulatory rather than inpatient settings.

PMID- 22467849
TI  - Hypoxia causes triglyceride accumulation by HIF-1-mediated stimulation of lipin 1
      expression.
AB  - Adaptation to hypoxia involves hypoxia-inducible transcription factors (HIFs) and
      requires reprogramming of cellular metabolism that is essential during both
      physiological and pathological processes. In contrast to the established role of
      HIF-1 in glucose metabolism, the involvement of HIFs and the molecular mechanisms
      concerning the effects of hypoxia on lipid metabolism are poorly characterized.
      Here, we report that exposure of human cells to hypoxia causes accumulation of
      triglycerides and lipid droplets. This is accompanied by induction of lipin 1, a
      phosphatidate phosphatase isoform that catalyzes the penultimate step in
      triglyceride biosynthesis, whereas lipin 2 remains unaffected. Hypoxic
      upregulation of lipin 1 expression involves predominantly HIF-1, which binds to a
      single distal hypoxia-responsive element in the lipin 1 gene promoter and causes
      its activation under low oxygen conditions. Accumulation of hypoxic triglycerides
      or lipid droplets can be blocked by siRNA-mediated silencing of lipin 1
      expression or kaempferol-mediated inhibition of HIF-1. We conclude that direct
      control of lipin 1 transcription by HIF-1 is an important regulatory feature of
      lipid metabolism and its adaptation to hypoxia.

PMID- 22467850
TI  - Both sequence and context are important for flagellar targeting of a glucose
      transporter.
AB  - Many of the cilia- and flagella-specific integral membrane proteins identified to
      date function to sense the extracellular milieu, and there is considerable
      interest in defining pathways for targeting such proteins to these sensory
      organelles. The flagellar glucose transporter of Leishmania mexicana, LmxGT1, is
      targeted selectively to the flagellar membrane, whereas two other isoforms,
      LmxGT2 and LmxGT3, are targeted to the pellicular plasma membrane of the cell
      body. To define the flagellar targeting signal, deletions and point mutations
      were generated in the N-terminal hydrophilic domain of LmxGT1, which mediates
      flagellar localization. Three amino acids, N95-P96-M97, serve critical roles in
      flagellar targeting, resulting in strong mistargeting phenotypes when
      mutagenized. However, to facilitate flagellar targeting of other non-flagellar
      membrane proteins, it was necessary to attach a larger region surrounding the NPM
      motif containing amino acids 81-113. Molecular modeling suggests that this region
      might present the critical NPM residues at the surface of the N-terminal domain.
      It is likely that the NPM motif is recognized by currently unknown protein
      binding partners that mediate flagellar targeting of membrane-associated
      proteins.

PMID- 22467851
TI  - DDA3 stabilizes microtubules and suppresses neurite formation.
AB  - We have previously shown that DDA3 - also known as proline/serine-rich coiled
      coil protein 1 (PSRC1) - is a microtubule-associated protein that promotes cell
      growth by stimulating the beta-catenin pathway. Here, we report that DDA3 can
      bundle and stabilize microtubules in vivo and in vitro. We found that
      overexpression of DDA3 increased the abundance of acetylated and tyrosinated
      microtubules. We employed PC12 and N2a cell lines, as well as cultured
      hippocampal neurons, and demonstrated that overexpression of DDA3 suppressed
      neurite/axon outgrowth, whereas its depletion accelerated neurite/axon formation
      and elongation. Knockdown of DDA3 reduced beta3-tubulin levels in N2a cells,
      which contributed to the spontaneous neurite formation caused by DDA3 depletion.
      Consistent with its role in suppressing neuritogenesis, DDA3 was downregulated
      during induced neuronal differentiation. Moreover, expression of DDA3 was
      detected in the rat brain at embryonic (E) day E15 and in the cortical region at
      E17, the period of active neurogenesis. Levels of cortical DDA3 decreased at the
      beginning of E19, when active neuritogenesis is completed. Overall our results
      demonstrate that DDA3 is a so-far-unknown microtubule-stabilizing protein that is
      involved in regulating neurite formation and elongation.

PMID- 22467852
TI  - The F-BAR domains from srGAP1, srGAP2 and srGAP3 regulate membrane deformation
      differently.
AB  - Coordination of membrane deformation and cytoskeletal dynamics lies at the heart
      of many biological processes critical for cell polarity, motility and
      morphogenesis. We have recently shown that Slit-Robo GTPase-activating protein 2
      (srGAP2) regulates neuronal morphogenesis through the ability of its F-BAR domain
      to regulate membrane deformation and induce filopodia formation. Here, we
      demonstrate that the F-BAR domains of two closely related family members, srGAP1
      and srGAP3 [designated F-BAR(1) and F-BAR(3), respectively] display significantly
      different membrane deformation properties in non-neuronal COS7 cells and in
      cortical neurons. F-BAR(3) induces filopodia in both cell types, though less
      potently than F-BAR(2), whereas F-BAR(1) prevents filopodia formation in cortical
      neurons and reduces plasma membrane dynamics. These three F-BAR domains can
      heterodimerize, and they act synergistically towards filopodia induction in COS7
      cells. As measured by fluorescence recovery after photobleaching, F-BAR(2)
      displays faster molecular dynamics than F-BAR(3) and F-BAR(1) at the plasma
      membrane, which correlates well with its increased potency to induce filopodia.
      We also show that the molecular dynamic properties of F-BAR(2) at the membrane
      are partially dependent on F-Actin. Interestingly, acute phosphatidylinositol 4,5
      bisphosphate [PtdIns(4,5)P(2)] depletion in cells does not interfere with plasma
      membrane localization of F-BAR(2), which is compatible with our result showing
      that F-BAR(2) binds to a broad range of negatively-charged phospholipids present
      at the plasma membrane, including phosphatidylserine (PtdSer). Overall, our
      results provide novel insights into the functional diversity of the membrane
      deformation properties of this subclass of F-BAR-domains required for cell
      morphogenesis.

PMID- 22467853
TI  - The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 function as
      ubiquitous and selective modulators of mammalian N-glycosylation.
AB  - Protein N-glycosylation is an essential modification that occurs in all
      eukaryotes and is catalysed by the oligosaccharyltransferase (OST) in the
      endoplasmic reticulum. Comparative studies have clearly shown that eukaryotic
      STT3 proteins alone can fulfil the enzymatic requirements for N-glycosylation,
      yet in many cases STT3 homologues form stable complexes with a variety of non
      catalytic OST subunits. Whereas some of these additional components might play a
      structural role, others appear to increase or modulate N-glycosylation efficiency
      for certain precursors. Here, we have analysed the roles of three non-catalytic
      mammalian OST components by studying the consequences of subunit-specific
      knockdowns on the stability and enzymatic activity of the OST complex. Our
      results demonstrate that OST48 and DAD1 are required for the assembly of both
      STT3A- and STT3B-containing OST complexes. The structural perturbations of these
      complexes we observe in OST48- and DAD1-depleted cells underlie their pronounced
      hypoglycosylation phenotypes. Thus, OST48 and DAD1 are global modulators of OST
      stability and hence N-glycosylation. We show that KCP2 also influences protein N
      glycosylation, yet in this case, the effect of its depletion is substrate
      specific, and is characterised by the accumulation of a novel STT3A-containing
      OST subcomplex. Our results suggest that KCP2 acts to selectively enhance the OST
      dependent processing of specific protein precursors, most likely co-translational
      substrates of STT3A-containing complexes, highlighting the potential for
      increased complexity of OST subunit composition in higher eukaryotes.

PMID- 22467854
TI  - Abp1 utilizes the Arp2/3 complex activator Scar/WAVE in bristle development.
AB  - Many developmental processes rely on cortical actin dynamics; however, the
      mechanisms of its fine control at the cell cortex are still largely unknown. Our
      analyses demonstrate that the lipid- and F-actin-binding protein Abp1 is crucial
      for actin-driven bristle development in Drosophila melanogaster. Combined
      genetic, cell biological and biochemical analyses reveal that Abp1 triggers
      cortical Arp2/3-mediated actin nucleation by complex formation with Scar in
      bristle development. The role of the plasma-membrane-associated Abp1 subpool was
      highlighted by constitutively membrane-anchored Abp1. Such gain-of-function
      experiments led to a severe split-bristle phenotype, which was negatively
      correlated with bristle length. This phenotype was dependent on Scar but not on
      WASP and required the Scar-interacting SH3 domain of Abp1. Strikingly, knockout
      of abp1 led to defects in both microchaete and macrochaete bristle integrity.
      Importantly, Arp2- and Scar-deficient flies displayed similar bristle phenotypes.
      Microchaetes of flies deficient for Abp1, Arp2 and Scar functions had kinks,
      whereas those of wasp heterozygous flies did not. Electron microscopy analyses
      revealed that abp1 knockout, Arp2 RNAi and Scar RNAi all led to distorted
      macrochaetes with an excessive number of ridges. Interestingly, despite the
      physical association of Abp1 with Scar and its ability to use the Arp2/3 complex
      activator as an effector, abp1 knockout did not affect Scar stability. This is in
      contrast to classical Scar complex components, such as Kette or Sra-1. Our work
      reveals that Abp1 is an important, Scar-interacting factor controlling cortical
      Arp2/3-mediated actin nucleation and unravels a novel layer of complexity in the
      scrupulous control of cortical actin nucleation during sensory organ formation.

PMID- 22467855
TI  - LRP1 mediates Hedgehog-induced endocytosis of the GPC3-Hedgehog complex.
AB  - Glypican-3 (GPC3) is a heparan sulfate (HS) proteoglycan that is bound to the
      cell membrane through a glycosylphosphatidylinositol link. This glypican
      regulates embryonic growth by inhibiting the hedgehog (Hh) signaling pathway.
      GPC3 binds Hh and competes with Patched (Ptc), the Hh receptor, for Hh binding.
      The interaction of Hh with GPC3 triggers the endocytosis and degradation of the
      GPC3-Hh complex with the consequent reduction of Hh available for binding to Ptc.
      Currently, the molecular mechanisms by which the GPC3-Hh complex is internalized
      remains unknown. Here we show that the low-density-lipoprotein receptor-related
      protein-1 (LRP1) mediates the Hh-induced endocytosis of the GPC3-Hh complex, and
      that this endocytosis is necessary for the Hh-inhibitory activity of GPC3.
      Furthermore, we demonstrate that GPC3 binds through its HS chains to LRP1, and
      that this interaction causes the removal of GPC3 from the lipid rafts domains.

PMID- 22467856
TI  - Dental pulp of the third molar: a new source of pluripotent-like stem cells.
AB  - Dental pulp is particularly interesting in regenerative medicine because of the
      accessibility and differentiation potential of the tissue. Dental pulp has an
      early developmental origin with multi-lineage differentiation potential as a
      result of its development during childhood and adolescence. However, no study has
      previously identified the presence of stem cell populations with embryonic-like
      phenotypes in human dental pulp from the third molar. In the present work, we
      describe a new population of dental pulp pluripotent-like stem cells (DPPSCs)
      that were isolated by culture in medium containing LIF, EGF and PDGF. These cells
      are SSEA4(+), OCT3/4(+), NANOG(+), SOX2(+), LIN28(+), CD13(+), CD105(+), CD34(-),
      CD45(-), CD90(+), CD29(+), CD73(+), STRO1(+) and CD146(-), and they show genetic
      stability in vitro based on genomic analysis with a newly described CGH
      technique. Interestingly, DPPSCs were able to form both embryoid-body-like
      structures (EBs) in vitro and teratoma-like structures that contained tissues
      derived from all three embryonic germ layers when injected in nude mice. We
      examined the capacity of DPPSCs to differentiate in vitro into tissues that have
      similar characteristics to mesoderm, endoderm and ectoderm layers in both 2D and
      3D cultures. We performed a comparative RT-PCR analysis of GATA4, GATA6, MIXL1,
      NANOG, OCT3/4, SOX1 and SOX2 to determine the degree of similarity between
      DPPSCs, EBs and human induced pluripotent stem cells (hIPSCs). Our analysis
      revealed that DPPSCs, hIPSC and EBs have the same gene expression profile.
      Because DPPSCs can be derived from healthy human molars from patients of
      different sexes and ages, they represent an easily accessible source of stem
      cells, which opens a range of new possibilities for regenerative medicine.

PMID- 22467857
TI  - Polycomb repressive complex 2 impedes intestinal cell terminal differentiation.
AB  - The crypt-villus axis constitutes the functional unit of the small intestine,
      where mature absorptive cells are confined to the villi, and stem cells and
      transit amplifying and differentiating cells are restricted to the crypts. The
      polycomb group (PcG) proteins repress differentiation and promote self-renewal in
      embryonic stem cells. PcGs prevent transcriptional activity by catalysing
      epigenetic modifications, such as the covalent addition of methyl groups on
      histone tails, through the action of the polycomb repressive complex 2 (PRC2).
      Although a role for PcGs in the preservation of stemness characteristics is now
      well established, recent evidence suggests that they may also be involved in the
      regulation of differentiation. Using intestinal epithelial cell models that
      recapitulate the enterocytic differentiation programme, we generated a RNAi
      mediated stable knockdown of SUZ12, which constitutes a cornerstone for PRC2
      assembly and functionality, in order to analyse intestinal cell proliferation and
      differentiation. Expression of SUZ12 was also investigated in human intestinal
      tissues, revealing the presence of SUZ12 in most proliferative epithelial cells
      of the crypt and an increase in its expression in colorectal cancers. Moreover,
      PRC2 disruption led to a significant precocious expression of a number of
      terminal differentiation markers in intestinal cell models. Taken together, our
      data identified a mechanism whereby PcG proteins participate in the repression of
      the enterocytic differentiation program, and suggest that a similar mechanism
      exists in situ to slow down terminal differentiation in the transit amplifying
      cell population.

PMID- 22467858
TI  - Rac1 acts in conjunction with Nedd4 and dishevelled-1 to promote maturation of
      cell-cell contacts.
AB  - The Rho-GTPase Rac1 promotes actin polymerization and membrane protrusion that
      mediate initial contact and subsequent maturation of cell-cell junctions. Here we
      report that Rac1 associates with the ubiquitin-protein ligase neural precursor
      cell expressed developmentally down-regulated 4 (Nedd4). This interaction
      requires the hypervariable C-terminal domain of Rac1 and the WW domains of Nedd4.
      Activated Rac1 colocalises with endogenous Nedd4 at epithelial cell-cell
      contacts. Reduction of Nedd4 expression by shRNA results in reduced
      transepithelial electrical resistance (TER) and concomitant changes in the
      distribution of adherens and tight junction markers. Conversely, expression of
      Nedd4 promotes TER, suggesting that Nedd4 cooperates with Rac1 in the induction
      of junctional maturation. We found that Nedd4, but not Nedd4-2, mediates the
      ubiquitylation and degradation of the adapter protein dishevelled-1 (Dvl1), the
      expression of which negatively regulates cell-cell contact. Nedd4-mediated
      ubiquitylation requires its binding to the C-terminal domain of Dvl1, comprising
      the DEP domain, and targets an N-terminal lysine-rich region upstream of the Dvl1
      DIX domain. We found that endogenous Rac1 colocalises with endogenous Dvl1 in
      intracellular puncta as well as on cell-cell junctions. Finally, activated Rac1
      was found to stimulate Nedd4 activity, resulting in increased ubiquitylation of
      Dvl1. Together, these data reveal a novel Rac1-dependent signalling pathway that,
      through Nedd4-mediated ubiquitylation of Dvl1, stimulates the maturation of
      epithelial cell-cell contacts.

PMID- 22467859
TI  - The function of the M-line protein obscurin in controlling the symmetry of the
      sarcomere in the flight muscle of Drosophila.
AB  - Obscurin (also known as Unc-89 in Drosophila) is a large modular protein in the M
      line of Drosophila muscles. Drosophila obscurin is similar to the nematode
      protein UNC-89. Four isoforms are found in the muscles of adult flies: two in the
      indirect flight muscle (IFM) and two in other muscles. A fifth isoform is found
      in the larva. The larger IFM isoform has all the domains that were predicted from
      the gene sequence. Obscurin is in the M-line throughout development of the
      embryo, larva and pupa. Using P-element mutant flies and RNAi knockdown flies, we
      have investigated the effect of decreased obscurin expression on the structure of
      the sarcomere. Embryos, larvae and pupae developed normally. In the pupa,
      however, the IFM was affected. Although the Z-disc was normal, the H-zone was
      misaligned. Adults were unable to fly and the structure of the IFM was irregular:
      M-lines were missing and H-zones misplaced or absent. Isolated thick filaments
      were asymmetrical, with bare zones that were shifted away from the middle of the
      filaments. In the sarcomere, the length and polarity of thin filaments depends on
      the symmetry of adjacent thick filaments; shifted bare zones resulted in
      abnormally long or short thin filaments. We conclude that obscurin in the IFM is
      necessary for the development of a symmetrical sarcomere in Drosophila IFM.

PMID- 22467860
TI  - PF19 encodes the p60 catalytic subunit of katanin and is required for assembly of
      the flagellar central apparatus in Chlamydomonas.
AB  - For all eukaryotic cilia the basal bodies provide a template for the assembly of
      the doublet microtubules, and intraflagellar transport provides a mechanism for
      transport of axonemal components into the growing cilium. What is not known is
      how the central pair of microtubules is nucleated or how their associated
      polypeptides are assembled. Here we report that the Chlamydomonas pf19 mutation
      results in a single amino acid change within the p60 catalytic subunit of
      katanin, and that this mutation prevents microtubule severing activity. The pf19
      mutant has paralyzed flagella that lack the central apparatus. Using a
      combination of mutant analysis, RNAi-mediated reduction of protein expression and
      in vitro assays, we demonstrate that the p60 catalytic subunit of the microtubule
      severing protein katanin is required for central apparatus assembly in
      Chlamydomonas. In addition, we show that in Chlamydomonas the microtubule
      severing activity of p60 katanin is not required for stress-induced
      deflagellation or cell cycle progression as has been previously reported.

PMID- 22467861
TI  - Phosphorylation of p35 and p39 by Cdk5 determines the subcellular location of the
      holokinase in a phosphorylation-site-specific manner.
AB  - Cdk5 is a member of the cyclin-dependent kinase (Cdk) family, which is activated
      by neuronal activators p35 or p39. Cdk5 regulates a variety of neuronal
      activities including migration, synaptic activity and neuronal death. p35 and p39
      impart cytoplasmic membrane association of p35-Cdk5 and p39-Cdk5, respectively,
      through their myristoylation, but it is not clearly understood how the cellular
      localization is related to different functions. We investigated the role of Cdk5
      activity in the subcellular localization of p35-Cdk5 and p39-Cdk5. Cdk5 activity
      affected the localization of p35-Cdk5 and p39-Cdk5 through phosphorylation of p35
      or p39. Using unphosphorylated or phosphomimetic mutants of p35 and p39, we found
      that phosphorylation at Ser8, common to p35 and p39, by Cdk5 regulated the
      cytoplasmic localization and perinuclear accumulation of unphosphorylated S8A
      mutants, and whole cytoplasmic distribution of phosphomimetic S8E mutants. Cdk5
      activity was necessary to retain Cdk5-activator complexes in the cytoplasm.
      Nevertheless, small but distinct amounts of p35 and p39 were detected in the
      nucleus. In particular, nuclear p35 and p39 were increased when the Cdk5 activity
      was inhibited. p39 had a greater propensity to accumulate in the nucleus than
      p35, and phosphorylation at Thr84, specific to p39, regulated the potential
      nuclear localization activity of the Lys cluster in p39. These results suggest
      that the subcellular localization of the Cdk5-activator complexes is determined
      by its kinase activity, and also implicate a role for p39-Cdk5 in the nucleus.

PMID- 22467862
TI  - High-curvature domains of the ER are important for the organization of ER exit
      sites in Saccharomyces cerevisiae.
AB  - Protein export from the endoplasmic reticulum (ER) to the Golgi apparatus occurs
      at specialized regions known as the ER exit sites (ERES). In Saccharomyces
      cerevisiae, ERES appear as numerous scattered puncta throughout the ER. We
      examined ERES within the peripheral ER, finding that the proteins comprising the
      ERES localize on high-curvature ER domains where curvature-stabilizing protein
      Rtn1 is present. Deltartn1 Deltartn2 Deltayop1 cells have fewer high-curvature ER
      domains, but ERES accumulate at the remaining high-curvature ER domains on the
      edge of expanded ER sheets. We propose that membrane curvature is a key geometric
      feature for the regulation of ERES localization. We also investigated a spatial
      relationship between ERES and Golgi cisternae. Golgi cisternae in S. cerevisiae
      are unstacked, dispersed, and moving in the cytoplasm with cis-cisternae
      positioned adjacent to ERES, whereas trans-cisternae are not. Morphological
      changes in the ER of Deltartn1 Deltartn2 Deltayop1 cells resulted in aberrant
      Golgi structures, including cis- and trans-markers, and there was reduced
      movement at ERES between expanded ER sheets and the plasma membrane.

PMID- 22467863
TI  - Radixin regulates cell migration and cell-cell adhesion through Rac1.
AB  - The ERM proteins ezrin, radixin and moesin are adaptor proteins that link plasma
      membrane receptors to the actin cytoskeleton. Ezrin and moesin have been
      implicated in cell polarization and cell migration, but little is known about the
      involvement of radixin in these processes. Here we show that radixin is required
      for migration of PC3 prostate cancer cells, and that radixin, but not ezrin or
      moesin, depletion by RNA interference increases cell spread area and cell-cell
      adhesion mediated by adherens junctions. Radixin depletion also alters actin
      organization, and distribution of active phosphorylated ezrin and moesin. Similar
      effects were observed in MDA-MB-231 breast cancer cells. The phenotype of radixin
      depleted cells is similar to that induced by constitutively active Rac1, and Rac1
      is required for the radixin knockdown phenotype. Radixin depletion also increases
      the activity of Rac1 but not Cdc42 or RhoA. Analysis of Rac guanine nucleotide
      exchange factors (GEFs) suggests that radixin affects the activity of Vav GEFs.
      Indeed, Vav GEF depletion reverses the phenotype of radixin knockdown and reduces
      the effect of radixin knockdown on Rac1 activity. Our results indicate that
      radixin plays an important role in promoting cell migration by regulating Rac1
      mediated epithelial polarity and formation of adherens junctions through Vav
      GEFs.

PMID- 22467864
TI  - A crucial role for Mim2 in the biogenesis of mitochondrial outer membrane
      proteins.
AB  - Most of the mitochondrial outer membrane (MOM) proteins contain helical
      transmembrane domains. Some of the single-span proteins and all known multiple
      span proteins are inserted into the membrane in a pathway that depends on the MOM
      protein Mitochondrial Import 1 (Mim1). So far it has been unknown whether
      additional proteins are required for this process. Here, we describe the
      identification and characterization of Mim2, a novel protein of the MOM that has
      a crucial role in the biogenesis of MOM helical proteins. Mim2 physically and
      genetically interacts with Mim1, and both proteins form the MIM complex. Cells
      lacking Mim2 exhibit a severely reduced growth rate and lower steady-state levels
      of helical MOM proteins. In addition, absence of Mim2 leads to compromised
      assembly of the translocase of the outer mitochondrial membrane (TOM complex),
      hampered mitochondrial protein import, and defects in mitochondrial morphology.
      In summary, the current study demonstrates that Mim2 is a novel central player in
      the biogenesis of MOM proteins.

PMID- 22467865
TI  - A crucial role for Ras suppressor-1 (RSU-1) revealed when PINCH and ILK binding
      is disrupted.
AB  - PINCH, integrin-linked kinase (ILK) and Ras suppressor-1 (RSU-1) are molecular
      scaffolding proteins that form a physical complex downstream of integrins, and
      have overlapping roles in cellular adhesion. In Drosophila, PINCH and ILK
      colocalize in cells and have indistinguishable functions in maintaining wing
      adhesion and integrin to actin linkage in the muscle. We sought to determine
      whether the direct physical interaction between PINCH and ILK was essential for
      their functions using transgenic flies expressing a version of PINCH with a point
      mutation that disrupts ILK binding (PINCH(Q38A)). We demonstrate that the PINCH
      ILK interaction is not required for viability, for integrin-mediated adhesion of
      the wing or muscle, or for maintaining appropriate localization or levels of
      either PINCH or ILK. These results suggest alternative modes for PINCH
      localization, stabilization and linkage to the actin cytoskeleton that are
      independent of a direct interaction with ILK. Furthermore, we identified a
      synthetic lethality in flies carrying both the PINCH(Q38A) mutation and a null
      mutation in the gene encoding RSU-1. This lethality does not result from PINCH
      mislocalization or destabilization, and illustrates a novel compensatory role for
      RSU-1 in maintaining viability in flies with compromised PINCH-ILK binding. Taken
      together, this work highlights the existence of redundant mechanisms in adhesion
      complex assembly that support integrin function in vivo.

PMID- 22467866
TI  - N-cadherin-mediated cell-cell adhesion promotes cell migration in a three
      dimensional matrix.
AB  - Cancer cells that originate from epithelial tissues typically lose epithelial
      specific cell-cell junctions, but these transformed cells are not devoid of cell
      cell adhesion proteins. Using hepatocyte-growth-factor-treated MDCK cells that
      underwent a complete epithelial-to-mesenchymal transition, we analyzed cell-cell
      adhesion between these highly invasive transformed epithelial cells in a three
      dimensional (3D) collagen matrix. In a 3D matrix, these transformed cells formed
      elongated multicellular chains, and migrated faster and more persistently than
      single cells in isolation. In addition, the cell clusters were enriched with
      stress-fiber-like actin bundles that provided contractile forces. N-cadherin
      knockdown cells failed to form cell-cell junctions or migrate, and the expression
      of the N-cadherin cytoplasmic or extracellular domain partially rescued the
      knockdown phenotype. By contrast, the expression of N-cadherin-alpha-catenin
      chimera rescued the knockdown phenotype, but individual cells within the cell
      clusters were less mobile. Together, our findings suggest that a dynamic N
      cadherin and actin linkage is required for efficient 3D collective migration.

PMID- 22467867
TI  - Physical and functional interaction between ribosomal protein L11 and the tumor
      suppressor ARF.
AB  - The ARF tumor suppressor protein activates p53 in response to oncogenic stress,
      whereas ribosomal protein L11 induces p53 following ribosomal stress. Both
      proteins bind to central, albeit non-overlapping, regions of MDM2 and suppress
      MDM2 activity toward p53. However, it is not known whether the two pathways are
      functionally connected. Here we show that ARF directly binds to L11 in vitro and
      in cells, which then forms a complex with MDM2 and p53. L11 collaboratively
      enhances ARF-induced p53 transcriptional activity and cell cycle arrest.
      Supporting these results, knocking down L11 reduces ARF-mediated p53 accumulation
      and alleviates ARF-induced cell cycle arrest. Interestingly, overexpression of
      ARF increases the levels of ribosome-free L11 and enhances the interaction of L11
      with MDM2 and p53. These results demonstrate that ARF activates p53, at least
      partly by induction of ribosomal stress, which results in L11 suppression of
      MDM2, and suggest that the ARF-MDM2-p53 and the L11-MDM2-p53 pathways are
      functionally connected.

PMID- 22467868
TI  - Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of
      cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25
      homolog A (CDC25A) expression in cancer.
AB  - The RNA-binding protein LIN28A regulates the translation and stability of a large
      number of mRNAs as well as the biogenesis of certain miRNAs in embryonic stem
      cells and developing tissues. Increasing evidence indicates that LIN28A functions
      as an oncogene promoting cancer cell growth. However, little is known about its
      molecular mechanism of cell cycle regulation in cancer. Using tissue microarrays,
      we found that strong LIN28A expression was reactivated in about 10% (7.1-17.1%)
      of epithelial tumors (six tumor types, n = 369). Both in vitro and in vivo
      experiments demonstrate that LIN28A promotes cell cycle progression in cancer
      cells. Genome-wide RNA-IP-chip experiments indicate that LIN28A binds to
      thousands of mRNAs, including a large group of cell cycle regulatory mRNAs in
      cancer and embryonic stem cells. Furthermore, the ability of LIN28A to stimulate
      translation of LIN28A-binding mRNAs, such as CDK2, was validated in vitro and in
      vivo. Finally, using a combined gene expression microarray and bioinformatics
      approach, we found that LIN28A also regulates CCND1 and CDC25A expression and
      that this is mediated by inhibiting the biogenesis of let-7 miRNA. Taken
      together, these results demonstrate that LIN28A is reactivated in about 10% of
      epithelial tumors and promotes cell cycle progression by regulation of both mRNA
      translation (let-7-independent) and miRNA biogenesis (let-7-dependent).

PMID- 22467869
TI  - rRNA genes are not fully activated in mouse somatic cell nuclear transfer
      embryos.
AB  - The well known and most important function of nucleoli is ribosome biogenesis.
      However, the nucleolus showed delayed development and malfunction in somatic cell
      nuclear transfer (NT) embryos. Previous studies indicated that nearly half rRNA
      genes (rDNA) in somatic cells were inactive and not transcribed. We compared the
      rDNA methylation level, active nucleolar organizer region (NORs) numbers,
      nucleolar proteins (upstream binding factor (UBF), nucleophosmin (B23))
      distribution, and nucleolar-related gene expression in three different donor
      cells and NT embryos. The results showed embryonic stem cells (ESCs) had the most
      active NORs and lowest rDNA methylation level (7.66 and 6.76%), whereas mouse
      embryonic fibroblasts (MEFs) were the opposite (4.70 and 22.57%). After the donor
      cells were injected into enucleated MII oocytes, cumulus cells and MEFs nuclei
      lost B23 and UBF signals in 20 min, whereas in ESC-NT embryos, B23 and UBF
      signals could still be detected at 60 min post-NT. The embryos derived from ESCs,
      cumulus cells, and MEFs showed the same trend in active NORs numbers (7.19 versus
      6.68 versus 5.77, p < 0.05) and rDNA methylation levels (6.36 versus 9.67% versus
      15.52%) at the 4-cell stage as that in donor cells. However, the MEF-NT embryos
      displayed low rRNA synthesis/processing potential at morula stage and had an
      obvious decrease in blastocyst developmental rate. The results presented clear
      evidences that the rDNA reprogramming efficiency in NT embryos was determined by
      the rDNA activity in donor cells from which they derived.

PMID- 22467870
TI  - Novel cyclotides and uncyclotides with highly shortened precursors from Chassalia
      chartacea and effects of methionine oxidation on bioactivities.
AB  - Cyclotides are a new class of plant biologics that display a diverse range of
      bioactivities with therapeutic potentials. They possess an unusual end-to-end
      cyclic backbone combined with a cystine knot arrangement, making them
      exceptionally stable to heat, chemical and enzymatic degradation. Currently, >200
      cyclotides have been discovered but only three naturally occurring linear
      variants (also known as uncyclotides) have been isolated. In this study, we
      report the discovery of 18 novel peptides, chassatides C1 to C18, composed of 14
      new cyclotides and four uncyclotides from Chassalia chartacea (Rubiaceae family).
      Thus far, this is the largest number of uncyclotides being reported in a single
      species. Activity testing showed that the uncyclotides not only retain the
      effectiveness but also are the most potent chassatides in the assays for
      antimicrobial, cytotoxic, and hemolytic activities. Genetic characterization of
      novel chassatides revealed that they have the shortest precursors of all known
      cyclotides hitherto isolated, which represents a new class of cyclotide
      precursors. This is the first report of cyclotide genes in a second genus, the
      Chassalia, other than the Hedyotis (Oldenlandia) of the Rubiaceae family. In
      addition, we also report the characterization of two Met-oxidized derivatives of
      chassatides C2 and C11. The oxidation of Met residue causes loss of
      bioactivities, strengthening the importance of the hydrophobic patch for membrane
      interaction.

PMID- 22467871
TI  - Posttranslational modification of cellular proteins by a ubiquitin-like protein
      in bacteria.
AB  - Posttranslational modification of proteins with ubiquitin and ubiquitin-like
      proteins plays important regulatory roles in eukaryotes. Although a homologous
      conjugation system has recently been reported in Archaea, there is no similar
      report in Bacteria. This report describes the identification of a ubiquitin-like
      conjugation system in the bacterium Thermus thermophilus. A series of in vivo
      analyses revealed that TtuB, a bacterial ubiquitin-like protein that functions as
      a sulfur carrier in tRNA thiouridine synthesis, was covalently attached to target
      proteins, most likely via its C-terminal glycine. The involvement of the
      ubiquitin-activating enzyme-like protein TtuC in conjugate formation and the
      attachments of TtuB to TtuC and TtuA, which are proteins required for tRNA
      thiouridine synthesis, were demonstrated. Mass spectrometry analysis revealed
      that lysine residues (Lys-137/Lys-226/Lys-229) of TtuA were covalently modified
      by the C-terminal carboxylate of TtuB. Intriguingly, a deletion mutant of a JAMM
      (JAB1/MPN/Mov34 metalloenzyme) ubiquitin isopeptidase homolog showed aberrant
      TtuB conjugates of TtuC and TtuA and an ~50% decrease in thiouridine amounts in
      tRNA. These results would support the hypothesis that thiouridine synthesis is
      regulated by TtuB-conjugation.

PMID- 22467872
TI  - Leukotoxin (Leukothera(r)) targets active leukocyte function antigen-1 (LFA-1)
      protein and triggers a lysosomal mediated cell death pathway.
AB  - Leukotoxin (LtxA) is a protein toxin that is secreted from the oral bacterium,
      Aggregatibacter actinomycetemcomitans. LtxA targets specifically the beta(2)
      integrin, leukocyte function antigen-1 (LFA-1) on white blood cells (WBCs) and
      causes cell death. LtxA preferentially targets activated WBCs and is being
      developed as a therapeutic agent for the treatment of WBC diseases such as
      hematologic malignancies and autoimmune/inflammatory diseases. However, the
      mechanism by which interaction between LtxA and LFA-1 results in cell death is
      not well understood. Furthermore, how LtxA preferentially recognizes activated
      WBCs is not known. We show here that LtxA interacts specifically with LFA-1 in
      the active (exposed) conformation. In THP-1 monocytes, LtxA caused rapid
      activation of caspases, but LtxA could overcome the inhibition of caspases and
      still intoxicate. In contrast, inhibiting the vesicular trafficking pathway or
      cathepsin D release from the lysosome resulted in significant inhibition of LtxA
      mediated cytotoxicity, indicating a more potent, lysosomal mediated cell death
      pathway. LtxA caused rapid disruption of the lysosomal membrane and release of
      lysosomal contents into the cytosol. Binding of LtxA to LFA-1 resulted in the
      internalization of both LtxA and LFA-1, with LtxA localizing specifically to the
      lysosomal compartment. To our knowledge, LtxA represents the first bacterial
      toxin shown to localize to the lysosome where it induces rapid cell death.

PMID- 22467873
TI  - G protein-coupled receptor kinase 5 phosphorylates nucleophosmin and regulates
      cell sensitivity to polo-like kinase 1 inhibition.
AB  - G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein
      coupled receptors, leading to their desensitization and endocytosis. GRKs have
      also been implicated in phosphorylating other classes of proteins and can
      localize in a variety of cellular compartments, including the nucleus. Here, we
      attempted to identify potential nuclear substrates for GRK5. Our studies reveal
      that GRK5 is able to interact with and phosphorylate nucleophosmin (NPM1) both in
      vitro and in intact cells. NPM1 is a nuclear protein that regulates a variety of
      cell functions including centrosomal duplication, cell cycle control, and
      apoptosis. GRK5 interaction with NPM1 is mediated by the N-terminal domain of
      each protein, and GRK5 primarily phosphorylates NPM1 at Ser-4, a site shared with
      polo-like kinase 1 (PLK1). NPM1 phosphorylation by GRK5 and PLK1 correlates with
      the sensitivity of cells to undergo apoptosis with cells having higher GRK5
      levels being less sensitive and cells with lower GRK5 being more sensitive to
      PLK1 inhibitor-induced apoptosis. Taken together, our results demonstrate that
      GRK5 phosphorylates Ser-4 in nucleophosmin and regulates the sensitivity of cells
      to PLK1 inhibition.

PMID- 22467874
TI  - p53 binding prevents phosphatase-mediated inactivation of diphosphorylated c-Jun
      N-terminal kinase.
AB  - c-Jun N-terminal kinase (JNK) is a serine/threonine phosphotransferase whose
      sustained activation in response to genotoxic stress promotes apoptosis. In
      Drosophila, the normally rapid JNK-dependent apoptotic response to genotoxic
      stress is significantly delayed in Dmp53 (Drosophila p53) mutants. Likewise, the
      extent of JNK activity after UV irradiation is dependent on p53 in murine
      embryonic fibroblasts with loss of p53 resulting in diminished JNK activity.
      Together, these results suggest that p53 potentiates the JNK-dependent response
      to genotoxic stress; however, the mechanism whereby p53 stimulates JNK activity
      remains undefined. Here, we demonstrate that both Drosophila and human p53 can
      directly stimulate JNK activity independently of p53-dependent gene
      transcription. Furthermore, we demonstrate that both the Drosophila and human p53
      orthologs form a physical complex with diphosphorylated JNK ((DP)JNK) both in
      vivo and in vitro, suggesting that the interaction is evolutionarily conserved.
      Focusing on human p53, we demonstrate that the interaction maps to the DNA
      binding domain (hp53(DBD)). Intriguingly, binding of p53(DBD) alone to (DP)JNK
      prevented its inactivation by MAPK phosphatase (MKP)-5; however, JNK was still
      able to phosphorylate c-Jun while in a complex with the p53(DBD). Apparent
      dissociation constants for the p53(DBD).(DP)JNK (274 +/- 14 nm) and MKP-5.(DP)JNK
      (55 +/- 8 nm) complexes were established; however, binding of MKP-5 and p53 to
      JNK was not mutually exclusive. Together, these results suggest that stress
      dependent increases in p53 levels potentiate JNK activation by preventing its
      rapid dephosphorylation by MKPs and that the simultaneous activation of p53 and
      JNK may constitute a "fail-safe" switch for the JNK-dependent apoptotic response.

PMID- 22467875
TI  - Specific domains in yeast translation initiation factor eIF4G strongly bias RNA
      unwinding activity of the eIF4F complex toward duplexes with 5'-overhangs.
AB  - During eukaryotic translation initiation, the 43 S ribosomal pre-initiation
      complex is recruited to the 5'-end of an mRNA through its interaction with the 7
      methylguanosine cap, and it subsequently scans along the mRNA to locate the start
      codon. Both mRNA recruitment and scanning require the removal of secondary
      structure within the mRNA. Eukaryotic translation initiation factor 4A is an
      essential component of the translational machinery thought to participate in the
      clearing of secondary structural elements in the 5'-untranslated regions of
      mRNAs. eIF4A is part of the 5'-7-methylguanosine cap-binding complex, eIF4F,
      along with eIF4E, the cap-binding protein, and the scaffolding protein eIF4G.
      Here, we show that Saccharomyces cerevisiae eIF4F has a strong preference for
      unwinding an RNA duplex with a single-stranded 5'-overhang versus the same duplex
      with a 3'-overhang or without an overhang. In contrast, eIF4A on its own has
      little RNA substrate specificity. Using a series of deletion constructs of eIF4G,
      we demonstrate that its three previously elucidated RNA binding domains work
      together to provide eIF4F with its 5'-end specificity, both by promoting
      unwinding of substrates with 5'-overhangs and inhibiting unwinding of substrates
      with 3'-overhangs. Our data suggest that the RNA binding domains of eIF4G provide
      the S. cerevisiae eIF4F complex with a second mechanism, in addition to the eIF4E
      cap interaction, for directing the binding of pre-initiation complexes to the 5'
      ends of mRNAs and for biasing scanning in the 5' to 3' direction.

PMID- 22467876
TI  - Multisite phosphorylation disrupts arginine-glutamate salt bridge networks
      required for binding of cytoplasmic linker-associated protein 2 (CLASP2) to end
      binding protein 1 (EB1).
AB  - A group of diverse proteins reversibly binds to growing microtubule plus ends
      through interactions with end-binding proteins (EBs). These +TIPs control
      microtubule dynamics and microtubule interactions with other intracellular
      structures. Here, we use cytoplasmic linker-associated protein 2 (CLASP2) binding
      to EB1 to determine how multisite phosphorylation regulates interactions with
      EB1. The central, intrinsically disordered region of vertebrate CLASP proteins
      contains two SXIP EB1 binding motifs that are required for EB1-mediated plus-end
      tracking in vitro. In cells, both EB1 binding motifs can be functional, but most
      of the binding free energy results from nearby electrostatic interactions. By
      employing molecular dynamics simulations of the EB1 interaction with a minimal
      CLASP2 plus-end-tracking module, we find that conserved arginine residues in
      CLASP2 form extensive hydrogen-bond networks with glutamate residues
      predominantly in the unstructured, acidic C-terminal tail of EB1. Multisite
      phosphorylation of glycogen synthase kinase 3 (GSK3) sites near the EB1 binding
      motifs disrupts this electrostatic "molecular Velcro." Molecular dynamics
      simulations and (31)P NMR spectroscopy indicate that phosphorylated serines
      participate in intramolecular interactions with and sequester arginine residues
      required for EB1 binding. Multisite phosphorylation of these GSK3 motifs requires
      priming phosphorylation by interphase or mitotic cyclin-dependent kinases (CDKs),
      and we find that CDK- and GSK3-dependent phosphorylation completely disrupts
      CLASP2 microtubule plus-end-tracking in mitosis.

PMID- 22467877
TI  - Molecular basis for binding and subtype selectivity of 1,4-benzodiazepine
      antagonist ligands of the cholecystokinin receptor.
AB  - Allosteric binding pockets in peptide-binding G protein-coupled receptors create
      opportunities for the development of small molecule drugs with substantial
      benefits over orthosteric ligands. To gain insights into molecular determinants
      for this pocket within type 1 and 2 cholecystokinin receptors (CCK1R and CCK2R),
      we prepared a series of receptor constructs in which six distinct residues in
      TM2, -3, -6, and -7 were reversed. Two novel iodinated CCK1R- and CCK2R-selective
      1,4-benzodiazepine antagonists, differing only in stereochemistry at C3, were
      used. When all six residues within CCK1R were mutated to corresponding CCK2R
      residues, benzodiazepine selectivity was reversed, yet peptide binding
      selectivity was unaffected. Detailed analysis, including observations of gain of
      function, demonstrated that residues 6.51, 6.52, and 7.39 were most important for
      binding the CCK1R-selective ligand, whereas residues 2.61 and 7.39 were most
      important for binding CCK2R-selective ligand, although the effect of substitution
      of residue 2.61 was likely indirect. Ligand-guided homology modeling was applied
      to wild type receptors and those reversing benzodiazepine binding selectivity.
      The models had high predictive power in enriching known receptor-selective
      ligands from related decoys, indicating a high degree of precision in pocket
      definition. The benzodiazepines docked in similar poses in both receptors, with
      C3 urea substituents pointing upward, whereas different stereochemistry at C3
      directed the C5 phenyl rings and N1 methyl groups into opposite orientations. The
      geometry of the binding pockets and specific interactions predicted for ligand
      docking in these models provide a molecular framework for understanding ligand
      selectivity at these receptor subtypes. Furthermore, the strong predictive power
      of these models suggests their usefulness in the discovery of lead compounds and
      in drug development programs.

PMID- 22467878
TI  - Regulation of the type IV secretion ATPase TrwD by magnesium: implications for
      catalytic mechanism of the secretion ATPase superfamily.
AB  - TrwD, the VirB11 homologue in conjugative plasmid R388, is a member of the large
      secretion ATPase superfamily, which includes ATPases from bacterial type II and
      type IV secretion systems, type IV pilus, and archaeal flagellae assembly. Based
      on structural studies of the VirB11 homologues in Helicobacter pylori and
      Brucella suis and the archaeal type II secretion ATPase GspE, a unified mechanism
      for the secretion ATPase superfamily has been proposed. Here, we have found that
      the ATP turnover of TrwD is down-regulated by physiological concentrations of
      magnesium. This regulation is exerted by increasing the affinity for ADP, hence
      delaying product release. Circular dichroism and limited proteolysis analysis
      indicate that magnesium induces conformational changes in the protein that
      promote a more rigid, but less active, form of the enzyme. The results shown here
      provide new insights into the catalytic mechanism of the secretion ATPase
      superfamily.

PMID- 22467879
TI  - Arsenic promotes ubiquitinylation and lysosomal degradation of cystic fibrosis
      transmembrane conductance regulator (CFTR) chloride channels in human airway
      epithelial cells.
AB  - Arsenic exposure significantly increases respiratory bacterial infections and
      reduces the ability of the innate immune system to eliminate bacterial
      infections. Recently, we observed in the gill of killifish, an environmental
      model organism, that arsenic exposure induced the ubiquitinylation and
      degradation of cystic fibrosis transmembrane conductance regulator (CFTR), a
      chloride channel that is essential for the mucociliary clearance of respiratory
      pathogens in humans. Accordingly, in this study, we tested the hypothesis that
      low dose arsenic exposure reduces the abundance and function of CFTR in human
      airway epithelial cells. Arsenic induced a time- and dose-dependent increase in
      multiubiquitinylated CFTR, which led to its lysosomal degradation, and a decrease
      in CFTR-mediated chloride secretion. Although arsenic had no effect on the
      abundance or activity of USP10, a deubiquitinylating enzyme, siRNA-mediated
      knockdown of c-Cbl, an E3 ubiquitin ligase, abolished the arsenic-stimulated
      degradation of CFTR. Arsenic enhanced the degradation of CFTR by increasing
      phosphorylated c-Cbl, which increased its interaction with CFTR, and subsequent
      ubiquitinylation of CFTR. Because epidemiological studies have shown that arsenic
      increases the incidence of respiratory infections, this study suggests that one
      potential mechanism of this effect involves arsenic-induced ubiquitinylation and
      degradation of CFTR, which decreases chloride secretion and airway surface liquid
      volume, effects that would be proposed to reduce mucociliary clearance of
      respiratory pathogens.

PMID- 22467880
TI  - Small ubiquitin-like modifier (SUMO) modification of zinc finger protein 131
      potentiates its negative effect on estrogen signaling.
AB  - Like ubiquitin, small ubiquitin-like modifier (SUMO) covalently attaches to
      specific target proteins and modulates their functional properties, including
      subcellular localization, protein dimerization, DNA binding, and transactivation
      of transcription factors. Diverse transcriptional co-regulator complexes regulate
      the ability of estrogen receptors to respond to positive and negative acting
      hormones. Zinc finger protein 131 (ZNF131) is poorly characterized but may act as
      a repressor of estrogen receptor alpha (ERalpha)-mediated trans-activation. Here,
      we identify ZNF131 as a target for SUMO modification and as a substrate for the
      SUMO E3 ligase human polycomb protein 2 (hPc2). We report that the SUMO
      interacting motif 1 (SIM1) and the C-box of hPc2 are critical regions required
      for ZNF131 SUMOylation and define the ZNF131 SUMOylation site as lysine 567. We
      further show that SUMO modification potentiates the negative effect of ZNF131 on
      estrogen signaling and consequently attenuates estrogen-induced cell growth in a
      breast cancer cell line. Our findings suggest that SUMOylation is a novel
      regulator of ZNF131 action in estrogen signaling and breast cancer cell
      proliferation.

PMID- 22467881
TI  - Responsiveness of the PedsQL to pain-related changes in health-related quality of
      life in pediatric sickle cell disease.
AB  - OBJECTIVE: To determine if caregiver report of the pediatric quality of life
      inventory (PedsQL) is responsive to changes in health-related quality of life
      (HRQL) associated with pain episodes in pediatric sickle cell disease (SCD).
      METHODS: 81 caregivers of children ages 2-19 years with SCD completed the PedsQL
      as part of routine psychosocial screenings at 2 time points, ranging from 6 to 18
      months apart. Frequency of SCD-related pain episodes between time points was
      assessed using medical chart review. RESULTS: The frequency of pain episodes
      between time points was a significant predictor of decreases in physical,
      psychosocial, and total HRQL, even after controlling for time interval,
      demographic, and medical variables. CONCLUSIONS: The caregiver report of the
      PedsQL appears to be a useful tool for capturing changes in HRQL over time
      associated with pain episodes in SCD.

PMID- 22467882
TI  - Commentary: A call to action to secure the future of pediatric psychology-
      resonating to the points of Rozensky and Janicke (2012).

PMID- 22467884
TI  - Commentary: social competence in children with chronic illness: the devil is in
      the details.

PMID- 22467883
TI  - Sexual experience among emotionally and behaviorally disordered students in
      therapeutic day schools: an ecological examination of adolescent risk.
AB  - OBJECTIVE: This study examined gender differences in family, peer, partner, and
      mental health characteristics related to sexual experience among emotionally and
      behaviorally disordered students in therapeutic day schools, a population at
      elevated risk for negative sexual health outcomes. METHODS: A total of 417 13- to
      20-year-old adolescents reported on their family functioning, peer and partner
      relationship characteristics, mental health problems, and self-reported sexual
      behavior. RESULTS: For boys and girls, peer influence and conduct problems
      predicted sexual experience, and family dysfunction was related to negative peer
      influence. Greater rejection sensitivity was related to less sexual experience
      for boys and girls. The final path model revealed indirect effects of family
      dysfunction on boys' but not girls' sexual experiences. CONCLUSIONS: Findings
      underscore the utility of an ecological approach to understand social and
      personal mechanisms that increase risk and mitigate negative outcomes among
      emotionally and behaviorally disordered boys and girls in therapeutic day
      schools.

PMID- 22467885
TI  - Multicenter study verifying a method of noninvasive continuous cardiac output
      measurement using pulse wave transit time: a comparison with intermittent bolus
      thermodilution cardiac output.
AB  - BACKGROUND: Many technologies have been developed for minimally invasive
      monitoring of cardiac output. Estimated continuous cardiac output (esCCO)
      measurement using pulse wave transit time is one noninvasive method. Because it
      does not require any additional sensors other than those for conducting 3 basic
      forms of monitoring (electrocardiogram, pulse oximeter wave, and noninvasive (or
      invasive) arterial blood pressure measurement), esCCO measurement is potentially
      useful in routine clinical circulatory monitoring for any patient including low
      risk patients. We evaluated the efficacy of noninvasive esCCO using pulse wave
      transit time in this multicenter study. METHODS: We compared esCCO and
      intermittent bolus thermodilution cardiac output (TDCO) in 213 patients, 139
      intensive care units (ICUs), and 74 operating rooms (ORs), at 7 participating
      institutions. We performed electrocardiogram, pulse oximetry, TDCO, and arterial
      blood pressure measurements in patients in ICUs and ORs; a single calibration was
      performed to measure esCCO continuously. TDCO measurement was performed once
      daily for ICU patients and every hour for OR patients, and just before the
      removal of the pulmonary arterial catheter from patients in both the ICU and OR.
      We evaluated esCCO against TDCO with correlation analysis and Bland and Altman
      analysis and also assessed the change of bias over time. Furthermore, we
      inspected the impact of change in systemic vascular resistance (SVR) on change in
      bias because abnormal SVR was assumed to be a factor contributing to the change
      of the bias. RESULTS: From among 588 esCCO and TDCO datasets (excluding
      calibration points), 587 datasets were analyzed for 213 patients. The analysis
      results show a correlation coefficient of 0.79 (P < 0.0001, 95% confidence limits
      of 0.756-0.819), a bias (mean difference between esCCO and TDCO) of 0.13 L/min
      (95% confidence interval of bias 0.04-0.22 L/min), and a precision (1 SD) of 1.15
      L/min (95% prediction interval was -2.13 to 2.39 L/min). There were no
      significant differences among 3 defined time intervals over 48 hours after
      calibration (repeated-measures analysis of variance P = 0.781) in the ICU. The
      influence of SVR on esCCO analysis showed a correlation coefficient between SVR
      and an error of 0.37 (P < 0.0001, 95% confidence interval 0.298-0.438).
      CONCLUSION: The efficacy of noninvasive esCCO technology was compared with TDCO
      in 213 cases. Five hundred eighty-seven datasets comparing esCCO and TDCO showed
      close correlation and small bias and precision, which were comparable to current
      arterial waveform analysis technologies.

PMID- 22467886
TI  - The variability of response to propofol is reduced when a clinical observation is
      incorporated in the control: a simulation study.
AB  - BACKGROUND: When using a target-controlled infusion of propofol to produce
      sedation, the operator assumes that the individual patient's pharmacokinetic
      parameters match those in the control system so that the specified effect-site
      target is achieved, and that the specified target is appropriate for the
      individual patient's sensitivity. These inaccuracies cascade, and this produces
      error in the desired level of sedation, termed "target error." To address this
      issue, we designed a control system that incorporates the operator's observation
      of loss of responsiveness to determine patient sensitivity. Our hypothesis was
      that this control system would reduce the impact of pharmacokinetic parameter
      error and uncertainty in sensitivity on the system's target error. METHODS: A
      novel control system was implemented that produces a slow transition in the
      probability of loss of responsiveness, providing the operator with greater
      resolution to observe the time of this transition. The system uses the time of
      this transition to infer the effect-site concentration associated with loss of
      responsiveness, and the infusion sequence necessary to maintain this
      concentration. We used computer simulation to generate a population of 10,000
      patients with randomly distributed pharmacokinetic parameters and sensitivity to
      propofol, and compared the target error of our system with that of a target
      controlled infusion system targeting the effect-site concentration associated
      with 50% probability of loss of responsiveness. RESULTS: Our system exhibited a
      target error of -0.75% +/- 8.96%, compared with 0% +/- 27.6% for target
      controlled infusion, reducing the variability in achieving the specified target
      by a factor of 3.1 compared with target-controlled infusion, which was
      significant at P < 0.0001. CONCLUSIONS: Our system reduces the impact of
      biological variability by including the operator in the control loop. The utility
      of this approach in clinical practice will require further evaluation.

PMID- 22467887
TI  - The impact of hematocrit on fibrin clot formation assessed by rotational
      thromboelastometry.
AB  - BACKGROUND: Rotational thromboelastometry (ROTEM(r))-based FIBTEM is used
      perioperatively to assess the extent of fibrin polymerization in whole blood. In
      FIBTEM, cytochalasin D eliminates the contribution of platelets to whole blood
      clotting, but changing levels in fibrin(ogen) and erythrocytes may differently
      affect clot formation. Because dynamic changes of hematocrit are not reflected in
      plasma fibrinogen measurements, we hypothesized that the lack of erythrocytes in
      isolated plasma measurements would affect the relationship between the Clauss
      method and whole blood-based FIBTEM during cardiac surgery. Therefore, in the
      current study we investigated the influence of perioperative hematocrit changes
      on FIBTEM and fibrinogen measurements. METHODS: Blood samples were collected from
      6 consenting healthy volunteers. FIBTEM tests were run before and after serial in
      vitro dilutions of whole blood with saline or autologous plasma (5:1, 2:1, and
      1:1 v/v). We then evaluated the relationship between FIBTEM-maximal clot firmness
      (MCF) and the Clauss fibrinogen method in relation to hematocrit values before
      and after cardiac surgery. Pearson correlation coefficients were determined
      between laboratory test results and ROTEM variables. RESULTS: Upon in vitro
      hematocrit reduction, FIBTEM-MCF was progressively decreased depending on the
      extent of saline dilution, but it was increased by 31% after 1:1 volume
      replacement with autologous plasma (P < 0.05). In samples from cardiac patients
      (150 measurements in 50 patients), the overall correlation coefficient between
      FIBTEM-MCF and plasma fibrinogen was 0.80 (P < 0.001). In hemodiluted blood
      samples (during surgery or at intensive care unit), FIBTEM-MCF 10 mm corresponded
      to plasma fibrinogen levels of 200 mg/dL. In the subgroup analysis (n = 50 each),
      according to hematocrit levels (<25%, >=25% to 30%, >=30%), plasma fibrinogen
      levels of 200 mg/dL corresponded to 11 mm, 10 mm, and 8 mm of FIBTEM-MCF,
      respectively. The correlation between FIBTEM-MCF and plasma fibrinogen was higher
      at lower hematocrit (<25%) than at higher hematocrit (>30%) (r = 0.88 and 0.67,
      respectively). CONCLUSIONS: Perioperative changes in hematocrit affect the
      correlation between plasma fibrinogen levels and FIBTEM-MCF values. The higher
      correlation between FIBTEM-MCF and plasma fibrinogen with lower hematocrit (<25%)
      indicates that FIBTEM is a practical method to determine the need for fibrinogen
      replacement in bleeding patients who typically develop perioperative anemia.

PMID- 22467888
TI  - Gabapentin augments the antihyperalgesic effects of diclofenac sodium through
      spinal action in a rat postoperative pain model.
AB  - BACKGROUND: Gabapentin and nonsteroidal antiinflammatory drugs (NSAIDs) attenuate
      postoperative pain and neuropathic pain in humans. The combination of gabapentin
      and NSAIDs is effective for postoperative pain and enhances functional recovery
      after surgery. Intrathecal administration of gabapentin or NSAIDs inhibits
      hyperalgesia in a rat postoperative pain model. However, there is no information
      on the effects of intrathecal administration of a combination of gabapentin and
      NSAIDs. We therefore investigated the effects of intrathecal administration of
      gabapentin and NSAIDs in a rat model of postoperative pain. METHODS: Rats were
      prepared for intrathecal catheters under halothane anesthesia. Two days after
      catheterization, gabapentin (4, 40, or 400 MUg per 20 MUL of saline), diclofenac
      sodium, a nonselective cyclooxygenase inhibitor (2, 20, or 200 MUg per 20 MUL of
      6% glucose), 20 MUL saline, 20 MUL 6% glucose, and a combination of gabapentin
      and diclofenac (40 MUg gabapentin + 20 MUg diclofenac and 4 MUg gabapentin + 2
      MUg diclofenac per 20 MUL 6% glucose) were injected intrathecally. We performed a
      hindpaw incision 30 minutes after injection. Each group consisted of 6 rats. The
      mechanical threshold was measured to evaluate secondary hyperalgesia using von
      Frey filaments before intrathecal catheterization and at 2 hours, and 1, 3, 5,
      and 7 days after paw incision. RESULTS: Gabapentin 400 MUg attenuated mechanical
      hyperalgesia for 7 days compared with the control group. Diclofenac 200 MUg
      inhibited hyperalgesia for 5 days compared with the control group. The 40 MUg
      gabapentin + 20 MUg diclofenac group had a significantly reduced secondary
      hyperalgesic response in 2 hours and 1 day compared with 40 MUg gabapentin and 20
      MUg diclofenac, respectively. The 4 MUg gabapentin + 2 MUg diclofenac group had a
      significantly reduced secondary hyperalgesic response in 2 hours and 1 day
      compared with 2 MUg diclofenac. The withdrawal threshold on the contralateral paw
      did not change compared with the preincision threshold. CONCLUSION: Intrathecal
      administration of gabapentin and diclofenac in combination reduced secondary
      hyperalgesia at doses having no antihyperalgesic effects when given individually.
      Our results suggest that gabapentin and diclofenac have an important role in
      postoperative pain reduction at the spinal level, and that gabapentin augments
      the antihyperalgesic effects of diclofenac through action in the spinal cord.

PMID- 22467889
TI  - Reduction in sodium content of local anesthetics for peripheral nerve blocks: a
      comparative evaluation of saline with 5% dextrose--a randomized controlled double
      blind study.
AB  - BACKGROUND: Commercially available local anesthetic drugs when diluted with
      normal saline have high sodium content. High perineural sodium concentration has
      been implicated in antagonizing the analgesic effects of local anesthetics by
      preventing and/or delaying neural blockade. Five percent dextrose is not known to
      cause any short- or long-term injury when injected around neural tissue. In this
      study, we prospectively compared and evaluated block characteristics when local
      anesthetic drug was diluted with these 2 different agents. METHODS: Patients
      scheduled for upper limb surgery were randomly assigned to receive axillary
      brachial plexus block with 0.5% ropivacaine (1% diluted with either 5% dextrose
      or normal saline). Motor and sensory block were tested every 5 minutes for 30
      minutes. Postoperatively, a telephone interview was conducted after 24 hours and
      7 days along with surgical follow-up at days 3, 10, and/or 14 to 28 days to
      document side effects, patient satisfaction, and time for block resolution. Any
      nerve deficits were followed until resolution. The primary outcome was time to
      onset of sensory nerve block. RESULTS: Five hundred fifty patients were recruited
      for this study. The mean time to complete sensory block was 18.3 +/- 6.1 minutes
      in the dextrose group and 22.5 +/- 6.4 minutes in the saline group (P < 0.001,
      95% confidence interval for mean difference 3.0-5.4 minutes). There were 5
      patients with clinical nerve deficits (no statistical difference between groups).
      CONCLUSIONS: Dilution with 5% dextrose provides earlier onset of axillary
      brachial plexus block with ropivacaine.

PMID- 22467890
TI  - Availability of anesthesia equipment in Chinese hospitals: is the safety of
      anesthesia patient care assured?
AB  - Availability of physiologic monitoring equipment to ensure the safe
      administration of anesthesia is an expected standard in many parts of the world.
      Many hospitals in China may not have an adequate quantity and variety of
      anesthesia delivery and patient monitoring equipment to assure safe
      administration of anesthesia patient care. We present some typical cases of
      hospitals of different sizes and located in regions with different economic
      levels; our data demonstrate that there is a lack of available anesthesia
      administration and patient monitoring equipment in small hospitals and hospitals
      in economically underdeveloped regions.

PMID- 22467891
TI  - Ultrasound-guided ilioinguinal/iliohypogastric nerve blocks for persistent
      inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled,
      crossover trial.
AB  - BACKGROUND: Ilioinguinal and iliohypogastric nerve blocks are used in the
      clinical management of persistent inguinal postherniorrhaphy pain, but no
      controlled studies have been published on the subject. In this controlled study,
      we investigated the analgesic and sensory effects of ultrasound-guided blocks of
      the ilioinguinal and iliohypogastric nerves with lidocaine. METHODS: A
      randomized, double-blind, placebo-controlled, crossover trial in 12 patients with
      severe persistent inguinal postherniorrhaphy pain, including a control group of
      12 healthy controls, was performed. Assessments included pain ratings under
      standardized conditions with numerical rating scale (0-10), sensory mapping to a
      cool roller, and quantitative sensory testing (QST), in the groin regions, before
      and after each ultrasound-guided block. A needle approach of 1 to 2 cm superior
      and medial to the anterior superior iliac spine was used. Outcomes were changes
      in pain ratings, sensory mapping, and QST compared with preblock values.
      Lidocaine responders were a priori defined by a pain reduction of >=80% after
      lidocaine block and <=25% after placebo block, nonresponders by pain reduction of
      <80% after lidocaine block and <=25% after placebo block, and placebo responders
      by pain reduction of >25% after placebo block. RESULTS: One of 12 pain patients
      was a lidocaine responder, 6 patients were nonresponders, and 5 patients were
      placebo responders. No consistent QST changes were observed in patients after the
      lidocaine block. In 10 of 12 healthy controls, a cool hypoesthesia area developed
      in the groin after the lidocaine block. Furthermore, QST assessments demonstrated
      significantly decreased suprathreshold heat pain perception in the groin after
      lidocaine versus placebo blocks (95% confidence interval = -3.5 to -0.5, P =
      0.008). CONCLUSION: Ultrasound-guided lidocaine blocks of the ilioinguinal and
      iliohypogastric nerves, at the level of the anterior superior iliac spine, are
      not useful in diagnosis and management of persistent inguinal postherniorrhaphy
      pain.

PMID- 22467892
TI  - Multiple reservoirs contribute to intraoperative bacterial transmission.
AB  - BACKGROUND: Intraoperative stopcock contamination is a frequent event associated
      with increased patient mortality. In the current study we examined the relative
      contributions of anesthesia provider hands, the patient, and the patient
      environment to stopcock contamination. Our secondary aims were to identify risk
      factors for stopcock contamination and to examine the prior association of
      stopcock contamination with 30-day postoperative infection and mortality.
      Additional microbiological analyses were completed to determine the prevalence of
      bacterial pathogens within intraoperative bacterial reservoirs. Pulsed-field gel
      electrophoresis was used to assess the contribution of reservoir bacterial
      pathogens to 30-day postoperative infections. METHODS: In a multicenter study,
      stopcock transmission events were observed in 274 operating rooms, with the first
      and second cases of the day in each operating room studied in series to identify
      within- and between-case transmission events. Reservoir bacterial cultures were
      obtained and compared with stopcock set isolates to determine the origin of
      stopcock contamination. Between-case transmission was defined by the isolation of
      1 or more bacterial isolates from the stopcock set of a subsequent case (case 2)
      that were identical to reservoir isolates from the preceding case (case 1).
      Within-case transmission was defined by the isolation of 1 or more bacterial
      isolates from a stopcock set that were identical to bacterial reservoirs from the
      same case. Bacterial pathogens within these reservoirs were identified, and their
      potential contribution to postoperative infections was evaluated. All patients
      were followed for 30 days postoperatively for the development of infection and
      all-cause mortality. RESULTS: Stopcock contamination was detected in 23% (126 out
      of 548) of cases with 14 between-case and 30 within-case transmission events
      confirmed. All 3 reservoirs contributed to between-case (64% environment, 14%
      patient, and 21% provider) and within-case (47% environment, 23% patient, and 30%
      provider) stopcock transmission. The environment was a more likely source of
      stopcock contamination than provider hands (relative risk [RR] 1.91, confidence
      interval [CI] 1.09 to 3.35, P = 0.029) or patients (RR 2.56, CI 1.34 to 4.89, P =
      0.002). Hospital site (odds ratio [OR] 5.09, CI 2.02 to 12.86, P = 0.001) and
      case 2 (OR 6.82, CI 4.03 to 11.5, P < 0.001) were significant predictors of
      stopcock contamination. Stopcock contamination was associated with increased
      mortality (OR 58.5, CI 2.32 to 1477, P = 0.014). Intraoperative bacterial
      contamination of patients and provider hands was linked to 30-day postoperative
      infections. CONCLUSIONS: Bacterial contamination of patients, provider hands, and
      the environment contributes to stopcock transmission events, but the surrounding
      patient environment is the most likely source. Stopcock contamination is
      associated with increased patient mortality. Patient and provider bacterial
      reservoirs contribute to 30-day postoperative infections. Multimodal programs
      designed to target each of these reservoirs in parallel should be studied
      intensely as a comprehensive approach to reducing intraoperative bacterial
      transmission.

PMID- 22467893
TI  - Isoflurane pretreatment preserves adenosine triphosphate-sensitive K(+) channel
      function in the human artery exposed to oxidative stress caused by high glucose
      levels.
AB  - BACKGROUND: Adenosine triphosphate (ATP)-sensitive K(+) channels contribute to
      significant regulatory mechanisms related to organ blood flow in both
      physiological and pathological conditions. High glucose impairs arterial ATP
      sensitive K(+) channel activity via superoxide production. However, the effects
      of anesthetics on this pathological process have not been evaluated in humans. In
      the present study, we investigated whether pretreatment with the volatile
      anesthetic isoflurane preserves ATP-sensitive K(+) channel activity in the human
      artery exposed to oxidative stress caused by high glucose. METHODS: All
      experiments were performed using human omental arteries without endothelium in
      the presence of d-glucose (5.5 mmol/L). Some arteries were treated with
      isoflurane (1.15% or 2.3%) in combination with d- or l-glucose (20 mmol/L) for 60
      minutes, and then only isoflurane was discontinued. Relaxation and
      hyperpolarization of arterial segments in response to an ATP-sensitive K(+)
      channel opener levcromakalim were evaluated using the isometric force recording
      or electrophysiological study, respectively. Superoxide production was determined
      by dihydroethidium fluorescence. Immunohistochemical analysis for a subunit of
      reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p47phox was
      performed. Data were evaluated using repeated-measures analysis of variance or a
      factorial analysis of variance as appropriate, followed by Scheffe test. RESULTS:
      The ATP-sensitive K(+) channel antagonist glibenclamide (10(-6) mol/L) abolished
      relaxation induced by cumulative addition of levcromakalim (10(-8) to 10(-5)
      mol/L) in arteries treated with l-glucose (20 mmol/L). Incubation with d-glucose
      (20 mmol/L) impaired the vasorelaxation induced by levcromakalim. The selective
      NADPH oxidase NOX2 inhibitor gp91ds-tat (10(-6) mol/L) and pretreatment with
      isoflurane (1.15% and 2.3%) restored relaxation in response to levcromakalim in
      arteries treated with d-glucose (20 mmol/L). Isoflurane (2.3%), gp91ds-tat (10(
      6) mol/L), and their combination similarly restored hyperpolarization in response
      to levcromakalim (3 * 10(-6) mol/L) in arteries treated with d-glucose (20
      mmol/L). Along with these results, isoflurane (2.3%) reduced superoxide
      production and the intracellular mobilization of the cytosolic NOX2 subunit
      p47phox toward smooth muscle cell membrane in arteries treated with d-glucose (20
      mmol/L). CONCLUSIONS: We have demonstrated for the first time a beneficial effect
      from the pretreatment with isoflurane on the isolated human artery. Pretreatment
      with isoflurane preserves ATP-sensitive K(+) channel activity in the human
      omental artery exposed to oxidative stress induced by high glucose, whereas the
      effect seems to be mediated by NADPH oxidase inhibition. Volatile anesthetics may
      protect human visceral arteries from malfunction caused by oxidative stress.

PMID- 22467894
TI  - The pharmacokinetics of ketorolac after single postoperative intranasal
      administration in adolescent patients.
AB  - BACKGROUND: Ketorolac tromethamine (ketorolac) administration reduces
      postoperative opioid requirements. The pharmacokinetic characteristics of
      intranasal ketorolac tromethamine in children have not been characterized. Our
      objective of this study was to determine the pharmacokinetics of a single
      intranasal dose of ketorolac in adolescent patients. METHODS: Twenty surgical
      patients, ages 12 to 17 years, were enrolled. After surgery, subjects received
      intranasal ketorolac 15 mg (weight <=50 kg) or 30 mg (weight >50 kg) using a
      proprietary administration system. Blood samples were obtained for ketorolac
      assay at baseline (within 15 minutes before the dose) and at 0.5, 1, 2, 3, 4, 6,
      8, 12, and 24 hours after the dose. A population analysis was undertaken using
      nonlinear mixed-effects models. Parameter estimates were standardized to a 70-kg
      person. RESULTS: The intranasal dosing in adolescents was well tolerated with
      minimal adverse effects. A 1-compartment model with first-order absorption and
      elimination was satisfactory to describe time-concentration profiles. Population
      parameter estimates (between subject variability) were clearance (CL/F) 2.05 L/h
      (60.5%), volume of distribution (V/F) 15.2 L (32.4%), absorption half-life
      (t(1/2)abs) 0.173 hour (25.0%). Time to peak concentration (Tmax) was 52 minutes
      (SD 6 minutes). CONCLUSION: Administration of ketorolac by the intranasal route
      resulted in a rapid increase in plasma concentration and may be a useful
      therapeutic alternative to IV injection in adolescents because plasma
      concentrations attained with the device are likely to be analgesic
      (investigational new drug no. 62,829).

PMID- 22467895
TI  - The ability of anesthesia providers to visually estimate systolic pressure
      variability using the "eyeball" technique.
AB  - BACKGROUND: Systemic arterial respiratory variation has been shown to be a
      reliable predictor of changes in cardiac output after fluid administration.
      Arterial respiratory variation is often estimated from visual examination of the
      arterial waveform tracing. Our goal in this study was to assess the ability of
      anesthesia providers to visually estimate systolic pressure variation (SPV) as a
      percentage of systolic blood pressure (SPV). METHODS: Fifty anesthesia providers
      were recruited and asked to visually examine 10 recorded arterial waveform
      tracings (played in real time), to estimate SPV, and to state whether or not a
      fluid bolus was indicated. After completion of the examination, the participants
      were shown the original tracings, the true value for SPV, and their estimate. The
      percentage of incorrect physician decisions to administer or not administer
      additional fluid was analyzed using a binomial proportion confidence interval.
      Clinical utility was also assessed using clinical significance analysis. Limits
      of agreement were analyzed using the nonparametric approach recommended by Bland
      and Altman. RESULTS: The mean bias was +1.2%. The nonparametric limits of
      agreement were -5.1 and 7.5%, and contained 82% of values. Actual physician
      decisions were incorrect 4.4% of the time (95% confidence interval [CI] 2.8% to
      6.6%). On the basis of the clinical significance analysis, only 1% of treatments
      based on the visual estimation would have been incorrect. CONCLUSION: Visual
      estimates of respiratory variation are within clinically reasonable limits 82% of
      the time and lead to erroneous management decisions in 4.4% of measurements.

PMID- 22467897
TI  - Unintentional dural puncture with a Tuohy needle increases risk of chronic
      headache.
AB  - BACKGROUND: Neuraxial analgesia is chosen by almost half of women who give birth
      in the United States. Unintentional dural puncture is the most common
      complication of this pain management technique, occurring in 0.4% to 6% of
      parturients. Severe positional headaches develop acutely in 70% to 80% of these
      parturients. Acute postdural puncture headaches are well known, but few studies
      have investigated long-term sequelae. We investigated the incidence of and risk
      factors for chronic headache and chronic back pain in parturients who experienced
      unintentional dural puncture with a 17-gauge Tuohy needle compared with matched
      controls. METHODS: In a case control design, 40 parturients who sustained
      unintentional dural puncture with a 17-gauge Tuohy needle over an 18-month period
      and 40 controls matched for age, weight, and time of delivery were recruited by
      telephone and 2 validated questionnaires were administered assessing headache and
      back pain symptoms 12 to 24 months after delivery. RESULTS: The incidence of
      chronic headaches in the study group (28%) was significantly higher than in the
      matched controls (5%) (OR = 7, P = 0.0129). Subjects who experienced dural
      punctures were more likely than controls to report chronic back pain (OR = 4, P =
      0.0250), but treatment with an epidural blood patch was not a risk factor for
      chronic back pain. CONCLUSIONS: Patients who incur unintentional dural punctures
      with large-gauge needles are surprisingly likely to continue to suffer chronic
      headaches. Treatment with an epidural blood patch does not enhance the risk of
      chronic back pain. The pathophysiology underlying these symptoms and the best
      treatment for this syndrome are not known.

PMID- 22467898
TI  - Effects of intrathecal morphine on transcranial electric motor-evoked potentials
      in adolescents undergoing posterior spinal fusion.
AB  - BACKGROUND: Intrathecal morphine (ITM) provides effective analgesia after
      posterior spinal fusion (PSF). Although most anesthetic drugs have well
      characterized effects on evoked potentials, there is little data on the effects
      of ITM on transcranial electric motor-evoked potentials (tceMEPs). We performed
      this study to assess the effects of ITM on tceMEPs in the first 30 minutes after
      administration. We hypothesized that administration of ITM in doses currently
      used at our institution would not significantly affect mean tceMEP amplitudes and
      latencies of an ITM study group relative to control patients who did not receive
      the drug. METHODS: tceMEPs were recorded before ITM injection and 5, 10, 20, and
      30 minutes after injection in 14 subjects ages 11 through 18 years undergoing
      PSF. These recordings were compared to an age-matched control group undergoing
      PSF in which ITM was not injected. The effects of ITM on tceMEP amplitude and
      latency were compared between the 2 groups. RESULTS: Fourteen subjects were
      enrolled in the ITM group and 16 served as controls. There were no significant
      differences in the baseline mean response amplitudes of the 2 groups for any of
      the 8 muscles studied. Mean response amplitudes over the 30-minute posttreatment
      period in the ITM group did not differ significantly from those of the control
      subjects. Average response amplitudes collapsed across all muscles for each
      subject were not significantly different during the baseline period (95% CI = 
      38% to 45%; P = 0.783), nor were they significantly different between the 2
      groups during the posttreatment period (95% CI = -30% to 78%; P = 0.640). There
      also were no significant differences in the mean response latencies of the 2
      groups in either the baseline or posttreatment periods. Average response
      latencies collapsed across all muscles for each subject were 4% larger for the
      ITM group than for controls during the baseline period (95% CI = -5% to 13%; P =
      0.377), and 3% larger for the ITM group than for controls during the
      posttreatment period (95% CI = -4% to 12%; P = 0.359). CONCLUSIONS:
      Administration of ITM in doses currently used at our institution did not cause
      more than a 70% attenuation of mean tceMEP amplitudes or latency changes of an
      ITM study group relative to control subjects during the 30-minute period after
      injection. Further studies are required to determine if there are delayed effects
      after this initial time period.

PMID- 22467899
TI  - Perioperative care for the older outpatient undergoing ambulatory surgery.
AB  - As the number of ambulatory surgery procedures continues to grow in an aging
      global society, the implementation of evidence-based perioperative care programs
      for the elderly will assume increased importance. Given the recent advances in
      anesthesia, surgery, and monitoring technology, the ambulatory setting offers
      potential advantages for elderly patients undergoing elective surgery. In this
      review article we summarize the physiologic and pharmacologic effects of aging
      and their influence on anesthetic drugs, the important considerations in the
      preoperative evaluation of elderly outpatients with coexisting diseases, the
      advantages and disadvantages of different anesthetic techniques on a procedural
      specific basis, and offer recommendations regarding the management of common
      postoperative side effects (including delirium and cognitive dysfunction,
      fatigue, dizziness, pain, and gastrointestinal dysfunction) after ambulatory
      surgery. We conclude with a discussion of future challenges related to the growth
      of ambulatory surgery practice in this segment of our surgical population. When
      information specifically for the elderly population was not available in the peer
      reviewed literature, we drew from relevant information in other ambulatory
      surgery populations.

PMID- 22467900
TI  - Volume-independent elastance: a useful parameter for open-lung positive end
      expiratory pressure adjustment.
AB  - BACKGROUND: A decremental positive end-expiratory pressure (PEEP) trial after
      full lung recruitment allows for the adjustment of the lowest PEEP that prevents
      end-expiratory collapse (open-lung PEEP). For a tidal volume (Vt) approaching
      zero, the PEEP of minimum respiratory system elastance (PEEP(minErs)) is
      theoretically equal to the pressure at the mathematical inflection point (MIP) of
      the pressure-volume curve, and seems to correspond to the open-lung PEEP in a
      decremental PEEP trial. Nevertheless, the PEEP(minErs) is dependent on Vt and
      decreases as Vt increases. To circumvent this dependency, we proposed the use of
      a second-order model in which the volume-independent elastance (E1) is used to
      set open-lung PEEP. METHODS: Pressure-volume curves and a recruitment maneuver
      followed by decremental PEEP trials, with a Vt of 6 and 12 mL/kg, were performed
      in 24 Wistar rats with acute lung injury induced by intraperitoneally injected (n
      = 8) or intratracheally instilled (n = 8) Escherichia coli lipopolysaccharide. In
      8 control animals, the anterior chest wall was surgically removed after PEEP
      trials, and the protocol was repeated. Airway pressure (Paw) and flow (F) were
      continuously acquired and fitted by the linear single-compartment model (Paw =
      Rrs.F + Ers.V + PEEP, where Rrs is the resistance of the respiratory system, and
      V is volume) and the volume-dependent elastance model (Paw = Rrs.F + E1 + E2.V.V
      + PEEP, where E2.V is the volume-dependent elastance). From each model, PEEPs of
      minimum Ers and E1 (PEEP(minE1)) were identified and compared with each
      respective MIP. The accuracy of PEEPminE1 and PEEPminErs in estimating MIP was
      assessed by bias and precision plots. Comparisons among groups were performed
      with the unpaired t test whereas a paired t test was used between the control
      group before and after chest wall removal and within groups at different Vts. All
      P values were then corrected for multiple comparisons by the Bonferroni
      procedure. RESULTS: In all experimental groups, PEEPminErs, but not PEEPminE1,
      tended to decrease as Vt increased. The difference between MIP and PEEPminE1
      exhibited a lower bias compared with the difference between MIP and PEEPminErs (P
      < 0.001). The PEEPminE1 was always significantly higher than the PEEPminErs (7.7
      vs 3.8, P < 0.001) and better approached MIP (7.7 vs 7.3 cm H2O with P = 0.04 at
      low Vt, and 7.8 vs 7.1 cm H2O with P < 0.001 at high Vt). CONCLUSIONS: PEEPminE1
      better identifies the open-lung PEEP independently of the adjusted Vt, and may be
      a practical, more individualized approach for PEEP titration.

PMID- 22467896
TI  - Intrathecal clonidine in the neonatal rat: dose-dependent analgesia and
      evaluation of spinal apoptosis and toxicity.
AB  - BACKGROUND: Neuraxial clonidine is used for perioperative analgesia in children
      of all ages. Preclinical studies in the postnatal rat allow comparison of the
      relative toxicity and safety of spinal analgesics throughout postnatal
      development. METHODS: Rat pups aged 3, 7, or 21 postnatal (P) days were briefly
      anesthetized for intrathecal injections of saline or clonidine. At each age, the
      maximum tolerated, antinociceptive (increased hindlimb mechanical withdrawal
      threshold) and antihyperalgesic (hindpaw carrageenan inflammation) doses were
      determined. Lumbar spinal cord sections were assessed for apoptosis and cell
      death (histology, activated caspase-3 immunohistochemistry, Fluoro-Jade C
      staining), histopathology (hematoxylin and eosin staining), and increased glial
      reactivity (microglial and astrocytic markers). P3 intrathecal ketamine sections
      served as positive controls. In additional groups, thermal latency and mechanical
      withdrawal threshold were measured at P35. RESULTS: Intrathecal clonidine
      produces age- and dose-dependent analgesia in rat pups. Maximal doses of
      clonidine did not alter the degree or distribution of apoptosis or increase glial
      reactivity in the neonatal spinal cord. No spinal histopathology was seen 1 or 7
      days after injection at any age. Intrathecal clonidine did not produce persistent
      changes in reflex sensitivity to mechanical or thermal stimuli at P35.
      CONCLUSIONS: Intrathecal clonidine in the postnatal rat did not produce signs of
      spinal cord toxicity, even at doses much larger than required for analgesia. The
      therapeutic ratio (maximum tolerated dose/antihyperalgesic dose) was >300 at P3,
      >30 at P7, and >10 at P21. These data provide additional information to inform
      the clinical choice of spinal analgesic drug in early life.

PMID- 22467901
TI  - Bernardino Ramazzini and women workers' health in the second half of the XVIIth
      century.
AB  - In the second half of the XVIIth century, pre-industrial society made extensive
      use of women's work. In his treatise, Diseases of Workers, published in 1700,
      Bernardino Ramazzini explored health conditions of women employed in different
      production sectors, describing their health problems and providing advice and
      remedies. This paper aims at reviewing his observations for women employed in
      different occupations, entailing exposure to dangerous materials and
      ergonomically challenging works.

PMID- 22467902
TI  - Correlation of treatment-emergent adverse events and clinical response to
      endocrine therapy in early breast cancer: a retrospective analysis of the German
      cohort of TEAM.
AB  - BACKGROUND: Previous studies have suggested a correlation between the occurrence
      of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment
      and improved clinical response. PATIENTS AND METHODS: A retrospective analysis of
      the German cohort of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial
      was carried out to assess disease-free survival (DFS) and overall survival (OS)
      in patients with and without arthralgia/myalgia and/or menopausal symptoms during
      adjuvant endocrine treatment. RESULTS: A total of 1502 patients were included;
      739 patients received tamoxifen followed by exemestane and 763 received
      exemestane. Patients reporting arthralgia/myalgia and patients reporting
      menopausal symptoms during endocrine treatment had significantly longer OS and
      DFS than those not reporting these events. The effect on OS was irrespective of
      treatment. DFS was significantly improved in exemestane-treated patients
      reporting arthralgia/myalgia or those reporting menopausal symptoms versus those
      not reporting these events. This effect on DFS was not observed in patients
      receiving sequential treatment. A combined analysis of patients reporting either
      menopausal symptoms or arthralgia/myalgia showed that OS and DFS were
      significantly improved in patients reporting one of these symptoms versus those
      not reporting either symptom. CONCLUSION: The occurrence of arthralgia/myalgia or
      menopausal symptoms during endocrine treatment is associated with significantly
      improved OS.

PMID- 22467903
TI  - Low prevalence of chronic hypertransaminasemia in a cohort of HIV-infected
      patients with no coinfections.

PMID- 22467904
TI  - Gems from distant shores: the 2012 Vilcek Foundation prizes.

PMID- 22467905
TI  - Family size and turnover rates among several classes of small non-protein-coding
      RNA genes in Caenorhabditis nematodes.
AB  - It is important to understand the forces that shape the size and evolutionary
      histories of gene families. Here, we investigated the evolution of non-protein
      coding RNA genes in the genomes of Caenorhabditis nematodes. We specifically
      focused on nested arrangements, that is, cases in which an RNA gene is entirely
      contained in an intron of another gene. Comparing these arrangements between
      species simplifies the inference of orthology and, therefore, of evolutionary
      fates of nested genes. Two distinct patterns are evident in the data. Genes
      encoding small nuclear RNAs (snRNAs) and transfer RNAs form large families, which
      have persisted since before the common ancestor of Metazoa. Yet, individual genes
      die relatively rapidly, with few orthologs having survived since the divergence
      of Caenorhabditis elegans and Caenorhabditis briggsae. In contrast, genes
      encoding small nucleolar RNAs (snoRNAs) are either single-copy or form small
      families. Individual snoRNAs turn over at a relatively slow rate-most C. elegans
      genes have clearly identifiable orthologs in C. briggsae. We also found that in
      Drosophila, genes from larger snRNA families die at a faster rate than their
      counterparts from single-gene families. These results suggest that a relationship
      between family size and the rate of gene turnover may be a general feature of
      genome evolution.

PMID- 22467906
TI  - OCAP: an open comprehensive analysis pipeline for iTRAQ.
AB  - MOTIVATION: Mass spectrometry-based iTRAQ protein quantification is a high
      throughput assay for determining relative protein expressions and identifying
      disease biomarkers. Processing and analysis of these large and complex data
      involves a number of distinct components and it is desirable to have a pipeline
      to efficiently integrate these together. To date, there are limited public
      available comprehensive analysis pipelines for iTRAQ data and many of these
      existing pipelines have limited visualization tools and no convenient interfaces
      with downstream analyses. We have developed a new open source comprehensive iTRAQ
      analysis pipeline, OCAP, integrating a wavelet-based preprocessing algorithm
      which provides better peak picking, a new quantification algorithm and a suite of
      visualizsation tools. OCAP is mainly developed in C++ and is provided as a
      standalone version (OCAP_standalone) as well as an R package. The R package
      (OCAP) provides the necessary interfaces with downstream statistical analysis.

PMID- 22467907
TI  - A subspace method for the detection of transcription factor binding sites.
AB  - MOTIVATION: The identification of the sites at which transcription factors (TFs)
      bind to Deoxyribonucleic acid (DNA) is an important problem in molecular biology.
      Many computational methods have been developed for motif finding, most of them
      based on position-specific scoring matrices (PSSMs) which assume the independence
      of positions within a binding site. However, some experimental and computational
      studies demonstrate that interdependences within the positions exist. RESULTS: In
      this article, we introduce a novel motif finding method which constructs a
      subspace based on the covariance of numerical DNA sequences. When a candidate
      sequence is projected into the modeled subspace, a threshold in the Q-residuals
      confidence allows us to predict whether this sequence is a binding site. Using
      the TRANSFAC and JASPAR databases, we compared our Q-residuals detector with
      existing PSSM methods. In most of the studied TF binding sites, the Q-residuals
      detector performs significantly better and faster than MATCH and MAST. As
      compared with Motifscan, a method which takes into account interdependences, the
      performance of the Q-residuals detector is better when the number of available
      sequences is small.

PMID- 22467908
TI  - GECA: a fast tool for gene evolution and conservation analysis in eukaryotic
      protein families.
AB  - SUMMARY: GECA is a fast, user-friendly and freely-available tool for representing
      gene exon/intron organization and highlighting changes in gene structure among
      members of a gene family. It relies on protein alignment, completed with the
      identification of common introns in the corresponding genes using CIWOG. GECA
      produces a main graphical representation showing the resulting aligned set of
      gene structures, where exons are to scale. The important and original feature of
      GECA is that it combines these gene structures with a symbolic display
      highlighting sequence similarity between subsequent genes. It is worth noting
      that this combination of gene structure with the indications of similarities
      between related genes allows rapid identification of possible events of gain or
      loss of introns, or points to erroneous structural annotations. The output image
      is generated in a portable network graphics format which can be used for
      scientific publications.

PMID- 22467909
TI  - DADP: the database of anuran defense peptides.
AB  - SUMMARY: Anuran tissues, and especially skin, are a rich source of bioactive
      peptides and their precursors. We here present a manually curated database of
      antimicrobial and other defense peptides with a total of 2571 entries, most of
      them in the precursor form with demarcated signal peptide (SP), acidic
      proregion(s) and bioactive moiety(s) corresponding to 1923 non-identical
      bioactive sequences. Search functions on the corresponding web server facilitate
      the extraction of six distinct SP classes. The more conserved of these can be
      used for searching cDNA and UniProtKB databases for potential bioactive peptides,
      for creating PROSITE search patterns, and for phylogenetic analysis.

PMID- 22467910
TI  - AutoLabDB: a substantial open source database schema to support a high-throughput
      automated laboratory.
AB  - MOTIVATION: Modern automated laboratories need substantial data management
      solutions to both store and make accessible the details of the experiments they
      perform. To be useful, a modern Laboratory Information Management System (LIMS)
      should be flexible and easily extensible to support evolving laboratory
      requirements, and should be based on the solid foundations of a robust, well
      designed database. We have developed such a database schema to support an
      automated laboratory that performs experiments in systems biology and high
      throughput screening. RESULTS: We describe the design of the database schema
      (AutoLabDB), detailing the main features and describing why we believe it will be
      relevant to LIMS manufacturers or custom builders. This database has been
      developed to support two large automated Robot Scientist systems over the last 5
      years, where it has been used as the basis of an LIMS that helps to manage both
      the laboratory and all the experiment data produced.

PMID- 22467911
TI  - Inferring gene regulatory networks by ANOVA.
AB  - MOTIVATION: To improve the understanding of molecular regulation events, various
      approaches have been developed for deducing gene regulatory networks from mRNA
      expression data. RESULTS: We present a new score for network inference, eta(2),
      that is derived from an analysis of variance. Candidate transcription
      factor:target gene (TF:TG) relationships are assumed more likely if the
      expression of TF and TG are mutually dependent in at least a subset of the
      examined experiments. We evaluate this dependency by eta(2), a non-parametric,
      non-linear correlation coefficient. It is fast, easy to apply and does not
      require the discretization of the input data. In the recent DREAM5 blind
      assessment, the arguably most comprehensive evaluation of inference methods, our
      approach based on eta(2) was rated the best performer on real expression
      compendia. It also performs better than methods tested in other recently
      published comparative assessments. About half of our predicted novel predictions
      are true interactions as estimated from qPCR experiments performed for DREAM5.
      CONCLUSIONS: The score eta(2) has a number of interesting features that enable
      the efficient detection of gene regulatory interactions. For most experimental
      setups, it is an interesting alternative to other measures of dependency such as
      Pearson's correlation or mutual information.

PMID- 22467912
TI  - Reno: regularized non-parametric analysis of protein lysate array data.
AB  - MOTIVATION: The reverse-phase protein lysate arrays have been used to quantify
      the relative expression levels of a protein in a number of cellular samples
      simultaneously. To avoid quantification bias due to mis-specification of commonly
      used parametric models, a nonparametric approach based on monotone response
      curves may be used. The existing methods, however, aggregate the protein
      concentration levels of replicates of each sample, and therefore fail to account
      for within-sample variability. RESULTS: We propose a method of regularization on
      protein concentration estimation at the level of individual dilution series to
      account for within-sample or within-group variability. We use an efficient
      algorithm to optimize an approximate objective function, with a data-adaptive
      approach to choose the level of shrinkage. Simulation results show that the
      proposed method quantifies protein concentration levels well. We show through the
      analysis of protein lysate array data from cell lines of different cancer groups
      that accounting for within-sample variability leads to better statistical
      analysis. AVAILABILITY: Code written in statistical programming language R is
      available at: http://odin.mdacc.tmc.edu/~jhhu/Reno

PMID- 22467913
TI  - Penalized logistic regression for high-dimensional DNA methylation data with case
      control studies.
AB  - MOTIVATION: DNA methylation is a molecular modification of DNA that plays crucial
      roles in regulation of gene expression. Particularly, CpG rich regions are
      frequently hypermethylated in cancer tissues, but not methylated in normal
      tissues. However, there are not many methodological literatures of case-control
      association studies for high-dimensional DNA methylation data, compared with
      those of microarray gene expression. One key feature of DNA methylation data is a
      grouped structure among CpG sites from a gene that are possibly highly
      correlated. In this article, we proposed a penalized logistic regression model
      for correlated DNA methylation CpG sites within genes from high-dimensional array
      data. Our regularization procedure is based on a combination of the l(1) penalty
      and squared l(2) penalty on degree-scaled differences of coefficients of CpG
      sites within one gene, so it induces both sparsity and smoothness with respect to
      the correlated regression coefficients. We combined the penalized procedure with
      a stability selection procedure such that a selection probability of each
      regression coefficient was provided which helps us make a stable and confident
      selection of methylation CpG sites that are possibly truly associated with the
      outcome. RESULTS: Using simulation studies we demonstrated that the proposed
      procedure outperforms existing main-stream regularization methods such as lasso
      and elastic-net when data is correlated within a group. We also applied our
      method to identify important CpG sites and corresponding genes for ovarian cancer
      from over 20 000 CpGs generated from Illumina Infinium HumanMethylation27K
      Beadchip. Some genes identified are potentially associated with cancers.

PMID- 22467914
TI  - Predicting giant transmembrane beta-barrel architecture.
AB  - MOTIVATION: The beta-barrel is a ubiquitous fold that is deployed to accomplish a
      wide variety of biological functions including membrane-embedded pores. Key
      influences of beta-barrel lumen diameter include the number of beta-strands (n)
      and the degree of shear (S), the latter value measuring the extent to which the
      beta-sheet is tilted within the beta-barrel. Notably, it has previously been
      reported that the shear value for small antiparallel beta-barrels (n<=24)
      typically ranges between n and 2n. Conversely, it has been suggested that the
      beta-strands in giant antiparallel beta-barrels, such as those formed by pore
      forming cholesterol-dependent cytolysins (CDC), are parallel relative to the axis
      of the beta-barrel, i.e. S=0. The S=0 arrangement, however, has never been
      observed in crystal structures of small beta-barrels. Therefore, the structural
      basis for how CDCs form a beta-barrel and span a membrane remains to be
      understood. RESULTS: Through comparison of molecular models with experimental
      data, we are able to identify how giant CDC beta-barrels utilize a 'near
      parallel' arrangement of beta-strands where S=n/2. Furthermore, we show how side
      chain packing within the beta-barrel lumen is an important limiting factor with
      respect to the possible shear values for small beta-barrels (n<=24 beta-strands).
      In contrast, our models reveal no such limitation restricts the shear value of
      giant beta-barrels (n>24 beta-strands). Giant beta-barrels can thus access a
      different architecture compared with smaller beta-barrels.

PMID- 22467915
TI  - DeOri: a database of eukaryotic DNA replication origins.
AB  - SUMMARY: DNA replication, a central event for cell proliferation, is the basis of
      biological inheritance. The identification of replication origins helps to reveal
      the mechanism of the regulation of DNA replication. However, only few eukaryotic
      replication origins were characterized not long ago; nevertheless, recent genome
      wide approaches have boosted the number of mapped replication origins. To gain a
      comprehensive understanding of the nature of eukaryotic replication origins, we
      have constructed a Database of Eukaryotic ORIs (DeOri), which contains all the
      eukaryotic ones identified by genome-wide analyses currently available. A total
      of 16 145 eukaryotic replication origins have been collected from 6 eukaryotic
      organisms in which genome-wide studies have been performed, the replication
      origin numbers being 433, 7489, 1543, 148, 348 and 6184 for humans, mice,
      Arabidopsis thaliana, Kluyveromyces lactis, Schizosaccharomyces pombe and
      Drosophila melanogaster, respectively. AVAILABILITY: Database of Eukaryotic ORIs
      (DeOri) can be accessed from http://tubic.tju.edu.cn/deori/

PMID- 22467916
TI  - Large-scale analysis of conserved rare codon clusters suggests an involvement in
      co-translational molecular recognition events.
AB  - MOTIVATION: An increasing amount of evidence from experimental and computational
      analysis suggests that rare codon clusters are functionally important for protein
      activity. Most of the studies on rare codon clusters were performed on a limited
      number of proteins or protein families. In the present study, we present the
      Sherlocc program and how it can be used for large scale protein family analysis
      of evolutionarily conserved rare codon clusters and their relation to protein
      function and structure. This large-scale analysis was performed using the whole
      Pfam database covering over 70% of the known protein sequence universe. Our
      program Sherlocc, detects statistically relevant conserved rare codon clusters
      and produces a user-friendly HTML output. RESULTS: Statistically significant rare
      codon clusters were detected in a multitude of Pfam protein families. The most
      statistically significant rare codon clusters were predominantly identified in N
      terminal Pfam families. Many of the longest rare codon clusters are found in
      membrane-related proteins which are required to interact with other proteins as
      part of their function, for example in targeting or insertion. We identified some
      cases where rare codon clusters can play a regulating role in the folding of
      catalytically important domains. Our results support the existence of a
      widespread functional role for rare codon clusters across species. Finally, we
      developed an online filter-based search interface that provides access to
      Sherlocc results for all Pfam families. AVAILABILITY: The Sherlocc program and
      search interface are open access and are available at
      http://bcb.med.usherbrooke.ca

PMID- 22467917
TI  - Highlight: our reptilian brethren: mammals and live-bearing lizards show similar
      pregnancy mechanisms.

PMID- 22467918
TI  - Sodium channel slow inactivation and adaptation in C-fibres.

PMID- 22467919
TI  - Reappraising I(h:) do myelinated motor and sensory axons of human peripheral
      nerves operate at different resting membrane potentials?

PMID- 22467920
TI  - Treating rheumatoid arthritis to target: a Canadian physician survey.
AB  - OBJECTIVE: To assess agreement and application of Treat to Target (T2T)
      recommendations in Canadian practice. METHODS: A survey of Canadian
      rheumatologists was conducted on the recommendations of T2T, an international
      initiative toward reaching specific therapeutic goals in rheumatoid arthritis.
      Agreement with each recommendation was measured on a 10-point Likert scale (1 =
      fully disagree, 10 = fully agree). A 4-point Likert scale (never, not very often,
      very often, always) assessed application of each recommendation in current
      practice. Responders who answered "never" or "not very often" were asked whether
      they were willing to change their practice according to the particular
      recommendation. RESULTS: Seventy-eight rheumatologists responded (24% of the 330
      who were contacted). The average agreement scores ranged from 6.92 for
      recommendation #5 (the frequency of measures of disease activity) to 9.10 for
      recommendation #10 (the patient needs to be involved in the decision-making
      process). A majority of participants indicated that they apply the T2T
      recommendations in their practice. Recommendations dealing with frequency of
      visits and the use of composite measures received the highest number of "never"
      or "not very often" responses. Busy practices and lack of confidence in composite
      outcome measures were the main reasons for objections to certain components of
      the recommendations. CONCLUSION: Although a majority of Canadian rheumatologists
      agreed with and supported the T2T recommendations, there was resistance toward
      specific aspects of these recommendations. Efforts are needed to better
      understand the reasons behind identified disagreements. Action plans to encourage
      the application of T2T recommendations in Canada are in development.

PMID- 22467921
TI  - Effect of rheumatoid arthritis on volumetric bone mineral density and bone
      geometry, assessed by peripheral quantitative computed tomography in
      postmenopausal women treated with bisphosphonates.
AB  - OBJECTIVE: To investigate the effect of rheumatoid arthritis (RA) on volumetric
      bone mineral density (vBMD) and bone geometry in postmenopausal women treated
      with bisphosphonates. METHODS: Fifty-three postmenopausal women with RA and 87
      control subjects, comparable in terms of age, body mass index, and years since
      menopause, underwent peripheral quantitative computed tomography (pQCT) of the
      nondominant tibia. RESULTS: At 4% (trabecular site), trabecular bone mineral
      content (BMC) and vBMD (p < 0.001) were lower in the RA group, while trabecular
      area was comparable. At 38% (cortical site), cortical BMC (p < 0.01), area (p <
      0.05), and thickness (p < 0.001) were lower in the RA group, whereas vBMD was
      comparable. Endosteal circumference was higher (p < 0.05), whereas periosteal
      circumference was comparable, indicating cancellization of cortical bone. In the
      RA group, muscle area was lower (p < 0.001), while at 14% polar stress strength
      index was significantly lower (p < 0.01) in patients with RA, indicating
      impairment of bone mechanical properties. CONCLUSION: RA is associated with
      negative effects on both cortical and cancellous bone in postmenopausal women
      treated with bisphosphonates. Cortical geometric properties are also adversely
      affected mainly by increased endosteal circumference, whereas trabecular
      geometric properties are generally preserved.

PMID- 22467922
TI  - Tocilizumab treatment decreases circulating myeloid dendritic cells and
      monocytes, 2 components of the myeloid lineage.
AB  - OBJECTIVE: Interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are
      proinflammatory cytokines involved in inflammatory response. Effective TNF-alpha
      blocker treatment is associated with an increase in circulating myeloid dendritic
      cells (mDC), suggesting their release from inflamed synovium. Currently, in vivo
      effects of IL-6 inhibition on DC are unknown. We monitored the changes in
      circulating mDC and plasmacytoid DC (pDC) during tocilizumab (TCZ) therapy in
      patients with rheumatoid arthritis (RA). METHODS: DC subset levels were evaluated
      by flow cytometry in patients with RA (n = 43) and in healthy volunteers (n =
      20). In patients with RA, these levels were measured before and during TCZ
      therapy (8 mg/kg every 4 weeks). Response to TCZ therapy was evaluated at 12
      weeks. Statistical analysis was based on Mann-Whitney U tests or Wilcoxon signed
      rank tests. RESULTS: At baseline, patients with active RA were characterized by a
      significantly lower level of circulating mDC and pDC compared to healthy donors.
      However, this difference did not correlate with any disease activity score. TCZ
      treated patients who met the European League Against Rheumatism (EULAR)
      improvement criteria at Week 12 had significant reductions in mDC and monocyte
      levels as compared with EULAR nonresponders. Levels of pDC, CD4+ T cells, and
      CD8+ T cells remained stable during the TCZ courses, regardless of treatment
      response. CONCLUSION: Our study reveals an unexpected reduction of circulating
      mDC and monocytes in patients with RA in response to TCZ therapy. In accord with
      reports on neutrophils and platelets decreasing during TCZ therapy, our data
      suggest an effect of IL-6 inhibition on cells from myeloid lineage.

PMID- 22467923
TI  - Peripheral blood gene expression and IgG glycosylation profiles as markers of
      tocilizumab treatment in rheumatoid arthritis.
AB  - OBJECTIVE: Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal
      antibody, has recently been approved as a biological therapy for rheumatoid
      arthritis (RA) and other diseases. It is not known if there are characteristic
      changes in gene expression and immunoglobulin G glycosylation during therapy or
      in response to treatment. METHODS: Global gene expression profiles from
      peripheral blood mononuclear cells of 13 patients with RA and active disease at
      Week 0 (baseline) and Week 4 following treatment were obtained together with
      clinical measures, serum cytokine levels using ELISA, and the degree of
      galactosylation of the IgG N-glycan chains. Gene sets separating responders and
      nonresponders were tested using canonical variates analysis. This approach also
      revealed important gene groups and pathways that differentiate responders from
      nonresponders. RESULTS: Fifty-nine genes showed significant differences between
      baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes
      determined responders after correction for multiple testing. Ten of the 12 genes
      with the most significant changes were validated using real-time quantitative
      polymerase chain reaction. An increase in the terminal galactose content of N
      linked glycans of IgG was observed in responders versus nonresponders, as well as
      in treated samples versus samples obtained at baseline. CONCLUSION: As a
      preliminary report, gene expression changes as a result of tocilizumab therapy in
      RA were examined, and gene sets discriminating between responders and
      nonresponders were found and validated. A significant increase in the degree of
      galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was
      documented.

PMID- 22467924
TI  - Interreader reliability in assessment of nailfold capillary abnormalities by
      beginners: pilot study of an intensive videocapillaroscopy training program.
AB  - OBJECTIVE: To test the learning curve of rheumatologists with different
      experience in videocapillaroscopy (VCP) attending an intensive training program
      focused on interpretation of the main capillary nailfold abnormalities, the
      scleroderma (systemic sclerosis, SSc) pattern, and the normal pattern, and to
      determine their interreader agreement with an experienced investigator. METHODS:
      Five investigators (1 senior, 1 junior, and 3 beginners) participated in the
      exercise. The study was composed of 2 steps. First, an independent investigator
      selected representative VCP images of normal patterns and capillary
      abnormalities. The second step included the training program, which ran 4 hours
      per day for 7 days. The senior rheumatologist taught investigators to recognize
      and interpret the normal pattern, the capillary abnormalities, and the different
      types of SSc pattern. These abnormalities were considered: homogeneously enlarged
      capillaries, giant capillaries, irregularly enlarged capillaries,
      microhemorrhages, neoangiogenesis, avascular areas, and capillary density.
      RESULTS: A total of 300 VCP images were read from all the investigators. Both
      kappa values and overall agreement percentages of qualitative and quantitative
      assessments showed progressive improvement from poor to excellent from the
      beginning to the end of the exercise. The sensitivity and specificity of the
      participants in the assessment of SSc pattern at the last lecture session were
      high. CONCLUSION: Our pilot study suggests that after an intensive 1-week
      training program, novice investigators with little or no experience in VCP are
      able to interpret the main capillary abnormalities and SSc pattern and to achieve
      good interreader agreement rates.

PMID- 22467925
TI  - High-dose intravenous immunoglobulin treatment increases regulatory T cells in
      patients with eosinophilic granulomatosis with polyangiitis.
AB  - OBJECTIVE: We studied the effects of intravenous immunoglobulin (IVIG) treatment
      on clinical symptoms and regulatory T (Treg) cell frequency in patients with
      eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Twenty-two EGPA
      patients with severe mononeuritis multiplex or cardiac dysfunction received IVIG
      therapy combined with conventional therapy (corticosteroid, immunosuppressants,
      or both). As a control, 24 EGPA patients without severe vasculitic symptoms were
      treated with conventional therapy. Before, during, and after treatment, we
      determined percentages of Treg cells and other relevant cells in patients'
      peripheral blood. RESULTS: The frequency of CD25+ among CD4+ T cells was lower at
      onset in the study group than in controls but increased significantly after IVIG
      treatment, relative to controls. The frequency of CD25+ among CD4+ T cells
      correlated with the frequency of FOXP3+ among CD4+ T cells and interleukin 10
      produced by CD25+CD4+ T cells. CONCLUSION: The increase in Treg cells seen with
      the combination of IVIG and conventional therapy may promote remission in EGPA.

PMID- 22467926
TI  - FCGR2A/CD32A and FCGR3A/CD16A variants and EULAR response to tumor necrosis
      factor-alpha blockers in psoriatic arthritis: a longitudinal study with 6 months
      of followup.
AB  - OBJECTIVE: The efficacy of antibody-based biological therapies currently used in
      psoriatic arthritis (PsA) depends not only on their blocking effect on the
      targeted molecule but also on their binding affinity to genetically defined
      variants of cell-surface Fc-gamma receptors. Our objective was to assess the
      potential influence of functionally relevant FCGR2A/CD32A (H131R) and
      FCGR3A/CD16A (V158F) genetic polymorphisms on the EULAR response to tumor
      necrosis factor-alpha (TNF-alpha) blocker therapy in PsA. METHODS: In total 103
      patients with PsA starting anti-TNF-alpha therapy were included. The efficacy of
      therapy was evaluated according to EULAR response criteria at 3 and 6 months.
      FCGR2A-R131H and FCGR3A-F158V polymorphisms were genotyped. Potential
      correlations between clinical response and the FCGR2A-R131H and FCGR3A-F158V
      polymorphisms were evaluated. RESULTS: EULAR response (moderate plus good) was
      85.4% at 3 months and 87.4% at 6 months, while good EULAR response was 61.2% and
      62.1%, respectively. More patients with high-affinity FCGR2A genotypes
      (homozygous or heterozygous combinations) achieved a EULAR response at 6 months
      compared to patients with the low-affinity genotype (RR; p = 0.034, adjusted
      comparison error rate < 0.025). This association was due mainly to the group of
      patients treated with etanercept. No correlation was found for the FCGR3A
      polymorphism. Similarly, no effect of C-reactive protein levels was observed.
      CONCLUSION: Our data indicate that FCGR2A polymorphism may influence the response
      to TNF-alpha blockers (namely etanercept) in PsA in a direction opposite to that
      previously found in patients with rheumatoid arthritis.

PMID- 22467928
TI  - Validity and responsiveness of the Dutch McMaster Toronto Arthritis Patient
      Preference Questionnaire (MACTAR) in patients with osteoarthritis of the hip or
      knee.
AB  - OBJECTIVE: To determine the content validity, the construct validity, and the
      responsiveness of the Dutch McMaster Toronto Arthritis Patient Preference
      Questionnaire (MACTAR) in patients with osteoarthritis (OA) of the hip or knee.
      METHODS: The MACTAR comprises 2 parts: a transitional part and a status part.
      Content validity was investigated by comparing patient-elicited activities to
      items on the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) and the Medical Outcomes Study Short-Form 36 (SF-36). Construct validity
      was determined by correlating MACTAR outcomes with WOMAC/SF-36 outcomes.
      Responsiveness was investigated by correlating MACTAR, WOMAC, and SF-36 change
      scores with patient global assessment (PGA) scores and plotting a receiver
      operating characteristics (ROC) curve. RESULTS: Eleven percent of the 894
      impaired activities, identified by 192 patients, were not represented in either
      the WOMAC or the SF-36. The correlations (r(s)) investigated for the MACTAR
      transitional part varied between 0.27 and -0.40; the status part correlated
      moderately with the general health scale of the SF-36 (r(s) = 0.44). MACTAR
      change scores correlated better with PGA than with WOMAC/SF-36 change scores. The
      area under the ROC curve amounted to 0.90. CONCLUSION: Our results suggest that
      the MACTAR exhibits moderate construct validity and good responsiveness in a
      population of patients with OA of the hip or knee. The MACTAR is potentially
      better able to detect changes over time in activities that are important to
      individual patients compared to other tools measuring physical function (WOMAC,
      SF-36). Clinicians could use the MACTAR to evaluate clinically relevant changes
      over time in patient-specific physical functioning.

PMID- 22467929
TI  - Increased incidence and impact of upper and lower gastrointestinal events in
      patients with rheumatoid arthritis in Olmsted County, Minnesota: a longitudinal
      population-based study.
AB  - OBJECTIVE: To assess the incidence and mortality impact of upper and lower
      gastrointestinal (GI) events in rheumatoid arthritis (RA) compared to non-RA
      subjects. METHODS: We identified incident upper and lower GI events and estimated
      their incidence rates using person-year methods in a population-based incident RA
      cohort of residents of Olmsted County, Minnesota, USA (1987 American College of
      Rheumatology criteria first fulfilled between January 1, 1980, and January 1,
      2008) and non-RA subjects from the same population. RESULTS: The study included
      813 patients with RA and 813 non-RA subjects (mean followup 10.3 and 10.8 yrs,
      respectively); 68% women; mean age 55.9 yrs in both cohorts. The rate of upper GI
      events/100 person-years was 2.9 in RA versus 1.7 in the non-RA cohort (rate ratio
      1.7, 95% CI 1.4, 2.2); for lower GI events, the rates were 2.1 in RA versus 1.4
      in the non-RA cohort (rate ratio 1.5, 95% CI 1.1, 1.9). The incidence of upper GI
      bleed, perforation, ulcer, obstruction, and any upper GI event in RA declined
      over calendar time; the incidence of lower GI events remained unchanged. Exposure
      to glucocorticoids, prior upper GI disease, abdominal surgery, and smoking were
      associated with lower GI events in RA. Both upper and lower GI events were
      associated with increased mortality risk in RA. CONCLUSION: There is increased
      risk of serious upper and lower GI events in RA compared to non-RA subjects, and
      increased GI-related mortality in RA. Prominent declines in incidence of upper,
      but not lower GI events in RA highlight the need for studies investigating lower
      GI disease in patients with RA.

PMID- 22467930
TI  - Effect of gastrointestinal manifestations on quality of life in 87 consecutive
      patients with systemic sclerosis.
AB  - OBJECTIVE: To assess the effect of gastrointestinal (GI) manifestation on the
      quality of life in patients with systemic sclerosis (SSc). METHODS: The
      University of California, Los Angeles Scleroderma Clinical Trial Consortium
      Gastrointestinal Tract 2 questionnaire was completed by 87 consecutive patients
      with SSc attending the scleroderma clinic at a single center. Their clinical
      features and current therapies were recorded; 100 patients with rheumatologic
      disorders other than SSc were used as controls. Individual scores were compared
      between SSc and controls, and between SSc subgroups. RESULTS: Of 87 patients, 76
      (90%) were women. Median age was 55 years and disease duration 105 months. Thirty
      three (38%) had diffuse and 54 (62%) had limited SSc. Patients with SSc had a
      higher score than controls in all domains (p < 0.05). Numbers of patients who
      responded positively to individual questionnaire components are as follows: any
      GI symptom 86 (99%), reflux 77 (89%), distension 73 (84%), soilage 19 (22%),
      diarrhea 44 (51%), constipation 51 (59%), well-being 43 (49%), and social 43
      (49%). There was no difference between the scores of patients with diffuse and
      limited disease subtypes. The use of calcium channel blockers did not
      significantly increase the constipation score (p = 0.99). Patients who responded
      positively to the reflux, distension, diarrhea, and constipation domains had
      lower scores in the well-being and social domains. CONCLUSION: GI manifestations,
      especially fecal incontinence (affecting 22% of patients), have a negative
      influence on the quality of life of patients with SSc. There was no difference
      between SSc disease subtypes.

PMID- 22467927
TI  - Heterogeneity of anticitrullinated peptide antibodies and response to anti-tumor
      necrosis factor agents in rheumatoid arthritis.
AB  - OBJECTIVE: To examine fine specificity of anticitrullinated peptide antibodies
      (ACPA) in relation to responsiveness to anti-tumor necrosis factor (anti-TNF)
      agents in rheumatoid arthritis (RA). METHODS: Samples from 450 patients with RA
      treated with anti-TNF agents were analyzed for antibodies to citrullinated alpha
      enolase, vimentin, and fibrinogen peptides. The Disease Activity Score-28 was
      measured at baseline and 6 months. RESULTS: Both anti-cFib antibodies and the
      number of citrullinated peptides recognized were associated with a poorer
      response. These findings were not significant following stratification for anti
      cyclic citrullinated peptide 2 antibodies. CONCLUSION: The presence of any ACPA
      rather than individual ACPA specificities was associated with a poorer response
      to anti-TNF agents. We suggest that this reflects distinctive differences in the
      pathogenesis of ACPA-positive and negative RA.

PMID- 22467931
TI  - Changes in regional brain morphology in neuropsychiatric systemic lupus
      erythematosus.
AB  - OBJECTIVE: Neuropsychiatric lupus (NPSLE) is a severe and potentially life
      threatening condition, reported to occur in 25%-70% of patients with systemic
      lupus erythematosus (SLE). Brain imaging, especially magnetic resonance imaging,
      is frequently used to diagnose or exclude overt cerebral pathologies such as
      edema, hemorrhage, and central thrombosis. More advanced imaging techniques have
      been applied to demonstrate subtle changes in regional cerebral blood flow and
      brain structure. We investigated changes in regional gray-matter (GM) volume in
      SLE patients without neurological manifestations and NPSLE patients at an acute
      stage of the disease. METHODS: Using high-resolution structural images and voxel
      based morphometry (VBM), we investigated regional GM volume in 20 NPSLE patients
      (within 2 weeks of the acute manifestation), 18 SLE patients without neurologic
      and/or psychiatric manifestations, and 18 healthy controls. RESULTS: VBM analyses
      revealed several regions of GM atrophy in various parts of the brain in NPSLE and
      SLE patients. GM atrophy was seen in both groups in the temporal and parietal
      lobes and was most pronounced in the posterior thalamus bilaterally. Both groups
      showed an increase in regional GM volume in the posterior parahippocampal gyrus.
      CONCLUSION: Our data suggest that changes in regional brain morphology are
      present in acute NPSLE, but also in SLE (as compared to controls), which might be
      indicative of a subclinical neurodegenerative process. Further research is needed
      to investigate whether specific neuropsychiatric symptoms are related to these
      changes.

PMID- 22467932
TI  - A prospective observational study of mycophenolate mofetil treatment in
      progressive diffuse cutaneous systemic sclerosis of recent onset.
AB  - OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF)
      treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc)
      of recent onset. METHODS: Twenty-five previously untreated consecutive patients
      with recent-onset (< 24 mo) diffuse progressive cutaneous SSc received MMF as the
      only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected
      body surface area (BSA) were compared from initiation of MMF to study end.
      Pulmonary function tests performed at the same institution before therapy and at
      study end were available in 15 patients. Histopathology and real-time PCR
      assessment of fibrosis-related gene expression were performed before and after
      treatment in skin biopsies from 3 patients. RESULTS: At 18.2 +/- 8.73 months of
      MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 +/- 8.62 to 14.52
      +/- 10.9 (p = 0.0004) and the affected BSA from 36% +/- 16% to 14% +/- 13.3% (p =
      0.00001). Pulmonary function tests remained stable from initiation of MMF to the
      end of the study. Skin histopathology showed a remarkable reduction in
      accumulation of fibrotic tissue. Real-time PCR of skin biopsies demonstrated a
      marked decrease in expression of fibrosis-related genes. CONCLUSION: Patients
      with diffuse progressive cutaneous SSc of recent onset treated with MMF
      experienced marked improvement in skin involvement and stabilization of pulmonary
      function. Skin biopsies from 3 patients demonstrated histopathological
      improvement and decreased expression of fibrosis-related genes.

PMID- 22467933
TI  - Longterm retention of tumor necrosis factor-alpha inhibitor therapy in a large
      italian cohort of patients with rheumatoid arthritis from the GISEA registry: an
      appraisal of predictors.
AB  - OBJECTIVE: To evaluate 4-year retention rates of tumor necrosis factor-alpha (TNF
      alpha) inhibitors adalimumab, etanercept, and infliximab among patients with
      longstanding rheumatoid arthritis (RA), as derived from an Italian national
      registry. METHODS: The clinical records of 853 adult patients with RA in the
      GISEA (Gruppo Italiano Studio Early Arthritis) registry were prospectively
      analyzed to compare drug survival rates and the baseline factors that may predict
      adherence to therapy. RESULTS: In 2003 and 2004, 324 patients started treatment
      with adalimumab, 311 with etanercept, and 218 with infliximab. After 4 years, the
      global retention rate of anti-TNF-alpha therapy was 42%. Etanercept survival
      (51.4%) was significantly better than that of infliximab (37.6%) or adalimumab
      (36.4%; p < 0.0001). Accordingly, the mean duration of therapy was significantly
      longer for etanercept (3.1 +/- 2 yrs) than for adalimumab (2.6 +/- 2 yrs) or
      infliximab (2.7 +/- 2 yrs; p < 0.05). The use of concomitant disease-modifying
      antirheumatic drugs, mainly methotrexate, and the presence of comorbidities
      significantly predicted drug continuation (p < 0.01), whereas a high Disease
      Activity Score did not. CONCLUSION: The 4-year global drug survival of
      adalimumab, etanercept, and infliximab was lower than 50%, with etanercept having
      the best retention rate. The main positive predictor of adherence to anti-TNF
      alpha therapy was the concomitant use of methotrexate. Our study provides further
      evidence that the real-life treatment of patients with RA may be different from
      that of randomized clinical trials.

PMID- 22467934
TI  - YouTube for information on rheumatoid arthritis--a wakeup call?
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a common debilitating autoimmune disease,
      with unmet need for knowledge among patients and the general population. YouTube
      is a popular, consumer-generated, video-sharing website, which can be a source of
      information on RA. We investigated the quality of information on RA on YouTube
      and analyzed audience interaction. METHODS: YouTube was searched using the term
      "Rheumatoid Arthritis," for videos uploaded on RA. Two physicians independently
      classified videos as useful, misleading, or patient views, and rated them on a 5
      point global quality scale (GQS; 1 = poor quality, 5 = excellent quality). Useful
      videos were rated for reliability and content, on a 5-point scale (higher scores
      represent more reliable and comprehensive videos). Source of videos was also
      noted. Audience interaction was assessed through video viewership. RESULTS: A
      total of 102 relevant videos were identified; 54.9% were classified as useful
      (GQS 2.9 +/- 1.0) and 30.4% deemed misleading (GQS 1.3 +/- 1.6). Mean reliability
      and content score of useful videos was 3.2 (+/- 1.0) and 2.5 (+/- 1.2),
      respectively. All videos uploaded by university channels and professional
      organizations provided useful information but formed only 12.7% of total videos,
      whereas 73.9% of medical advertisements and videos by for-profit organizations
      were misleading. There was no difference in the viewership/day (10.0 vs 21.5; p =
      nonsignificant) of useful and misleading information. CONCLUSION: YouTube is a
      source of information on RA, of variable quality, with wide viewership and
      potential to influence patients' knowledge and behavior. Physicians and
      professional organizations should be aware of and embrace this evolving
      technology to raise awareness about RA, and empower patients to discriminate
      useful from misleading information.

PMID- 22467935
TI  - Longitudinal evolution of risk of coronary heart disease in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To produce evidence on the longitudinal evolution of risk factors for
      coronary heart disease (CHD) in patients with systemic lupus erythematosus (SLE).
      METHODS: Based on data for 115 patients from the Montreal General Hospital Lupus
      Clinic (1971-2003) and for 4367 control subjects from the Framingham Offspring
      Study (1971-1994), we investigated the temporal evolution of total serum
      cholesterol, systolic blood pressure (SBP), body mass index (BMI), blood glucose,
      and estimated risk for CHD (reflecting the balance of changes in different risk
      factors). In analyses limited to patients with SLE, we assessed the effect of SLE
      duration on each risk factor, adjusting for age, calendar time, sex, baseline
      level of the risk factor, and medication use. Next, we assessed how the adjusted
      difference in the values of the risk factors between SLE and controls changes
      over time. RESULTS: Among patients with SLE, longer disease duration was
      independently associated with higher SBP and blood glucose levels. Compared with
      controls, these patients appeared to have accelerated rates of increase in total
      cholesterol, blood glucose, and overall estimated CHD risk. The rate of increase
      in BMI was lower in patients with SLE than in controls. CONCLUSION: Elevated CHD
      risk in patients with SLE appears to be at least partially mediated by
      accelerated increases in some CHD risk factors, longitudinal trajectories of
      which increasingly diverge over time from those of population controls.

PMID- 22467936
TI  - Challenging the diagnosis of primary angiitis of the central nervous system: a
      single-center retrospective study.
AB  - OBJECTIVE: (1) To describe a series of adults assessed for suspected primary
      angiitis of the central nervous system (PACNS) and their final diagnosis; (2) to
      describe and compare presenting features of PACNS and reversible cerebral
      vasoconstriction syndrome (RCVS); and (3) to evaluate the specificity of the
      presenting features of RCVS. METHODS: Patients evaluated at our institution
      between 2000 and 2008 for a possible CNS vasculitis and investigated by
      conventional angiography and/or brain biopsy were retrospectively analyzed. The
      inclusion criteria were a clinicoradiological presentation and cerebral
      angiography and/or brain biopsy raising the hypothesis of isolated cerebral
      vasculitis; and absence of identifiable etiology at the time of conventional
      angiogram and/or brain biopsy. RESULTS: Among 58 cases evaluated, 37 met the
      inclusion criteria and 33 were included in the study. Thirteen patients had RCVS.
      Thunderclap headaches, the absence of a focal neurological deficit, a convexal
      subarachnoid hemorrhage and/or normal brain parenchyma on magnetic resonance
      imaging, and "string of beads" appearance on conventional angiography had high
      diagnostic value. Six patients had other noninflammatory vascular disorders
      (intracranial atherosclerosis, cryptogenic embolism, and genetic vasculopathy).
      Six patients had infection or malignancy. Eight patients were diagnosed with
      PACNS; their clinical presentation and disease course were heterogeneous. Brain
      biopsy was performed in 3 cases (positive in 1). CONCLUSION: RCVS is an important
      differential diagnosis of CNS vasculitis. Its particular presentation should
      allow rapid identification in order to avoid pointless investigations and
      treatment. The frequent lack of histological proof and heterogeneous presentation
      of PACNS illustrated the nosological uncertainties of this label.

PMID- 22467937
TI  - Tumor necrosis factor-alpha inhibitor use is not associated with lipid changes in
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine the association of use of tumor necrosis factor-alpha
      (TNF-alpha) inhibitors with differences in lipid levels in patients with
      rheumatoid arthritis (RA). METHODS: We studied 807 patients with incident RA to
      compare differences in lipid levels in TNF-alpha inhibitor users versus nonusers,
      with adjustment for relevant covariables. RESULTS: TNF-alpha inhibitor use was
      not associated with differences in levels of low-density lipoprotein (LDL), high
      density lipoprotein (HDL), total cholesterol (TC), triglycerides, LDL:HDL, or
      TC:HDL compared to nonusers. CONCLUSION: Use of TNF-alpha inhibitor was not
      associated with differences in lipid levels in patients with RA.

PMID- 22467938
TI  - A valid formulation of the analysis of noninferiority trials under random effects
      meta-analysis.
AB  - A noninferiority (NI) trial is sometimes employed to show efficacy of a new
      treatment when it is unethical to randomize current patients to placebo because
      of the established efficacy of a standard treatment. Under this framework, if the
      NI trial determines that the treatment advantage of the standard to the new drug
      (i.e. S-N) is less than the historic advantage of the standard to placebo (S-P),
      then the efficacy of the new treatment (N-P) is established indirectly. We
      explicitly combine information from the NI trial with estimates from a random
      effects model, allowing study-to-study variability in k historic trials. Existing
      methods under random effects, such as the synthesis method, fail to account for
      the variability of the true standard versus placebo effect in the NI trial. Our
      method effectively uses a prediction interval for the missing standard versus
      placebo effect rather than a confidence interval of the mean. The consequences
      are to increase the variance of the synthesis method by incorporating a
      prediction variance term and to approximate the null distribution of the new
      statistic with a t with k-1 degrees of freedom instead of the standard normal.
      Thus, it is harder to conclude NI of the new to (predicted) placebo, compared
      with traditional methods, especially when k is small or when between study
      variability is large. When the between study variances are nonzero, we
      demonstrate substantial Type I error rate inflation with conventional approaches;
      simulations suggest that the new procedure has only modest inflation, and it is
      very conservative when between study variances are zero. An example is used to
      illustrate practical issues.

PMID- 22467939
TI  - The effect of riboflavin-ultraviolet A-induced collagen cross-linking on
      intraocular pressure measurement: an experimental study.
AB  - PURPOSE: To investigate the effect of corneal collagen cross-linking (CCL) on
      tonopen measurements of intraocular pressure (IOP). METHODS: CCL with 0.1%
      riboflavin solution and 30 min of ultraviolet A radiation was performed on the
      right eye of 15 New Zealand albino adult rabbits (1.8-2.4 kg) (15 eyes). The left
      eye served as control. IOP was measured by a pressure transducer system (true
      IOP) and by the tonopen hand-held device (corneal applanation tonometer) before
      treatment, at 1 week, 1 month and 3 months following CCL. Reference pressure in
      the globe was increased by increments of 10 mm Hg from 10 to 40 mm Hg, using an
      anterior chamber infusion on a stand with variable height, and tonopen IOP
      measurements were recorded for each reference pressure in both eyes. RESULTS:
      Before CCL, tonopen readings were similar between the two eyes (p>0.05). Tonopen
      underestimated the true IOP in all cases. Following CCL treatment, IOP
      measurements were significantly higher in the treated eye, at all time intervals
      (0.005<p<0.03). The most significant difference between true and measured IOP was
      noted at a reference pressure of 20 mm Hg. CONCLUSIONS: IOP measurements
      following CCL are overestimated by the tonopen, probably due to increased
      stiffness of the treated cornea.

PMID- 22467940
TI  - Acute episode of eyelid oedema. Blepharochalasis.

PMID- 22467941
TI  - Phenotypic plasticity of human umbilical vein endothelial cells.

PMID- 22467942
TI  - Comment on: 'Plasma, aqueous and vitreous homocysteine levels in proliferative
      diabetic retinopathy'.

PMID- 22467944
TI  - Osteoarthritis, exercise, and knee replacement.

PMID- 22467945
TI  - Exercise and osteoarthritis: not necessarily an all-or-nothing proposition!

PMID- 22467946
TI  - Anti-citrullinated peptide/protein antibodies and structural prognosis of
      rheumatoid arthritis: quantity versus quality.

PMID- 22467947
TI  - Fibromyalgia and enthesitis in psoriatic arthritis. Time to "characterize" and
      "refine" clinical definitions.

PMID- 22467949
TI  - Gouty arthritis of the ankle masquerading as a talus fracture.

PMID- 22467948
TI  - Clinical correlates of CENP-A and CENP-B antibodies in a large cohort of patients
      with systemic sclerosis.
AB  - OBJECTIVE: To study the clinical phenotypes of centromeric proteins (CENP)-A- and
      CENP-B-positive patients with systemic sclerosis (SSc) and to compare them to
      anticentromere antibody (ACA)-positive and negative SSc patients. METHODS: Sera
      samples were collected from 802 patients with SSc enrolled in a multicenter
      cohort study. Antibodies to CENP-A and B were detected by ELISA, and ACA by
      indirect immunofluorescence. Associations with clinical and other serological
      manifestations of SSc were investigated. RESULTS: CENP-A antibodies were detected
      in 276 (34%), CENP-B in 286 (36%), and ACA in 279 (35%) patients. Patients having
      ACA, CENP-A, and/or CENP-B resembled each other and differed from the remainder
      of the cohort in the following respects: older chronologically and at disease
      onset; more commonly women; more likely to have limited disease and lower skin
      scores; less likely to have finger ulcers, digital tuft resorption, or finger
      contractures; more likely to have pulmonary hypertension; less likely to have
      interstitial lung disease, scleroderma renal crisis, inflammatory arthritis, and
      inflammatory myositis; and having lower overall disease severity. CENP-A and/or B
      status was predictive of the extent of skin involvement over time. Patients with
      limited disease who were CENP-A-negative at baseline were more likely to progress
      to diffuse disease compared to CENP-A-positive patients (OR 2.55, 95% CI 1.37,
      4.85, p = 0.004). CONCLUSION: Clinical immunology laboratories are increasingly
      using high-throughput ELISA tests for CENP antibodies, with or without ACA
      detected by indirect immunofluorescence. The phenotype of CENP-A and/or B
      positive patients is generally similar to that associated with ACA.

PMID- 22467950
TI  - Posterior reversible encephalopathy syndrome.

PMID- 22467951
TI  - Could increased vascular endothelial growth factor induced by interleukin 17 be
      the cause of posterior reversible encephalopathy syndrome in systemic lupus
      erythematosus?

PMID- 22467952
TI  - High-titer Anti-aquaporin-4-IgG-associated Myelitis in Rhupus Syndrome.

PMID- 22467953
TI  - Clarification of the modified radiographic damage scoring method for gout.

PMID- 22467954
TI  - Clinical relevance of MEFV gene mutations in Japanese patients with unexplained
      fever.

PMID- 22467955
TI  - Does a joint count calibration exercise make a difference? Implications for
      clinical trials and training.

PMID- 22467956
TI  - Amyloidosis and giant cell arteritis/polymyalgia rheumatica.

PMID- 22467957
TI  - Teaching basic rheumatology.

PMID- 22467958
TI  - Antioxidant Activities and Oxidative Stabilities of Some Unconventional Oilseeds.
AB  - The oils of some unconventional oilseeds (hemp, radish, terebinth, stinging
      nettle, laurel) were obtained by a cold-press method in which the total oil
      content, fatty acids, tocopherol isomers, some metal contents (Ca, Mg, Fe, Cu),
      antioxidant activity and oxidative stability were determined. The total oil
      content was determined ranging between 30.68 and 43.12%, and the oil samples had
      large amounts of unsaturated fatty acids, with oleic acid and linoleic acid. Of
      all the oils, terebinth seed oil had the highest alpha-tocopherol content (102.21
      +/- 1.01 mg/kg oil). Laurel oilseed had the highest antiradical activity in both
      the DPPH and ABTS assays. The peroxide value of the non-oxidized oils ranged
      between 0.51 and 3.73 mequiv O(2)/kg oil. The TBARS value of the non-oxidized
      oils ranged between 0.68 +/- 0.02 and 6.43 +/- 0.48 mmol MA equiv/g oil. At 110 
      degrees C, the Rancimat induction period of the oils ranged between 1.32 and
      43.44 h. The infrared spectra of the samples were recorded by FTIR spectroscopy.
      The absorbance values of the spectrum bands were observed and it was determined
      that some of the chemical groups of oxidized oils caused changes in absorbance.
      As a result of the present research, the analyzed oils could be evaluated as an
      alternative to traditionally consumed vegetable oils or as additives to them.

PMID- 22467959
TI  - The oceans are not in good health.

PMID- 22467960
TI  - An ethicist's commentary on licensing boards dictating therapies.

PMID- 22467961
TI  - A survey for small animal veterinarians regarding flea and tick control pesticide
      products.
AB  - The Canadian Veterinary Medical Association administered a survey to capture the
      clinical experiences of small animal veterinarians regarding adverse effects
      observed in cats and dogs following the use of flea and tick control pesticide
      products. Results of this survey are discussed and compared with pesticide
      incident reports collected by Health Canada.

PMID- 22467962
TI  - Selenium status at the end of the grazing season, reproductive performance and
      degenerative myopathy in beef herds.
AB  - The objectives of this study were to describe the serum selenium (Se)
      concentrations of beef cows from herds with varying levels of reproductive
      success, to examine factors associated with the Se concentrations at the end of
      the grazing season, and to determine if there were any associations between serum
      Se and reproductive success or calf viability. In the fall of 2001, 781 serum
      samples from 66 herds were analyzed as part of a nested case-control study to
      investigate risk factors for fertility; 10.6% were deficient in Se (< 0.025 ppm)
      and 86.8% were less than adequate (< 0.08 ppm). Low serum Se was most common in
      thin cows where feed Se was < 0.2 ppm, and from areas with more precipitation or
      with black or gray soils. Serum Se at pregnancy testing was not associated with
      an increased risk of reproductive failure. Lower herd serum Se was associated
      with increased risk of identifying degenerative myopathy in the subsequent calf
      crop (P = 0.006).

PMID- 22467963
TI  - Effect of subcutaneous selenium injection and supplementary selenium source on
      blood selenium and glutathione peroxidase in feedlot heifers.
AB  - This study measured the effect on glutathione peroxidase (GSH-Px) and selenium
      (Se) in whole blood and plasma associated with subcutaneous Se injections in beef
      heifers fed organic or inorganic Se. Heifers (n = 120) were randomly divided into
      2 groups, 1 of which received subcutaneous Se injections. Both groups were given
      the same total mixed ration with 3 mg of organic or inorganic Se daily. Until
      week 2, heifers that had received Se injections showed higher concentrations of
      plasma Se and GSH-Px and whole blood Se (P < 0.001) than those having had no
      injections. Concentrations of plasma Se and GSH-Px were higher in the group
      receiving organic Se than the group receiving inorganic Se. Whole blood GSH-Px
      concentrations increased significantly (P < 0.001) throughout a 12-week period
      but were not affected by Se source. Combination of Se injections and
      supplementation could help maintain normal Se and GSH-Px blood status in beef
      heifers during the first few weeks in the feedlot.

PMID- 22467964
TI  - Microbiological baseline study of beef and pork carcasses from provincially
      inspected abattoirs in Alberta, Canada.
AB  - In 2006 and 2007 beef and pork carcass swabs from provincially inspected
      abattoirs in Alberta, Canada were tested to determine the levels of total aerobic
      bacteria, coliform bacteria, and generic Escherichia coli, and the prevalence of
      Salmonella spp., Campylobacter spp., and Shiga toxin-producing E. coli (STEC).
      Swabs from beef and pork carcasses from 48 and 34 facilities, respectively, were
      analyzed. All samples tested were positive for aerobic bacteria with 99.8% of
      beef and 96.0% of pork samples, having total counts of <= 100 000 CFU/cm(2).
      Coliform bacteria were isolated from 22.4% and 42.0% of beef and pork carcass
      samples, respectively. Generic E. coli were recovered from 14.6% of beef and
      33.7% of pork carcass samples. For beef carcasses, positive tests were obtained
      for 0.1% of 1036 samples tested for Salmonella spp., 1.5% of 1022 samples tested
      for Campylobacter spp. and 5.4% of 1018 samples tested for STEC. For pork
      carcasses, positive tests were obtained for 1.6 % of 1076 samples tested for
      Salmonella spp., 8.8% of 1070 samples tested for Campylobacter spp. and 4.8% of
      1067 samples tested for STEC.

PMID- 22467965
TI  - Surgical versus non-surgical treatment of feline small intestinal adenocarcinoma
      and the influence of metastasis on long-term survival in 18 cats (2000-2007).
AB  - This study retrospectively evaluated long-term outcomes of 18 cats diagnosed with
      small intestinal adenocarcinoma, based on surgical versus non-surgical treatment
      and the presence or absence of metastasis at the time of surgery. Ten cats had
      surgery and histopathologic confirmation of adenocarcinoma and 8 cats did not
      have surgery but had cytologic diagnosis of adenocarcinoma. Median survival of
      cats with adenocarcinoma that underwent surgical excision was 365 days and 22
      days for those with suspected adenocarcinoma that did not undergo surgery (P =
      0.019). Median survival of cats was 843 days for those without evidence of
      metastatic disease at the time of surgery and 358 days for those that had (P =
      0.25). In conclusion, surgical excision is beneficial in the treatment of small
      intestinal adenocarcinoma in the cat, including those patients with metastasis,
      and may result in a significantly longer survival time compared with patients
      which do not have their mass surgically excised.

PMID- 22467966
TI  - Incidence of meniscal injury in cats with cranial cruciate ligament ruptures.
AB  - This retrospective study evaluated the incidence of meniscal injury in cats with
      cranial cruciate ligament (CCL) ruptures. Medical records for cats diagnosed with
      CCL ruptures treated by a lateral fabellotibial suture (LFS) were reviewed for
      signalment, history, physical examination and surgical findings. Ninety-five cats
      (98 stifles) met the inclusion criteria. The incidence of meniscal injuries in
      feline CCL deficient stifles was 67%. Isolated medial meniscal injuries were
      found in 55 stifles (56%), isolated lateral meniscal injuries were found in 5
      stifles (5%), and lateral and medial meniscal injuries were found in 6 stifles
      (6%). There was no correlation between the presence of a meniscal injury and age,
      breed, sex, weight, duration of lameness, presence of concurrent medial patellar
      luxation, degree of degenerative joint disease, or presenting side of lameness.
      Given the high rate of meniscal pathology in cats with CCL ruptures, exploratory
      surgery for meniscal assessment and concurrent stifle stabilization should be
      considered in feline patients.

PMID- 22467967
TI  - Optimal filling solution for silicone Foley catheter balloons.
AB  - We assessed whether saline, sterile water, or air better maintained filling
      volume and diameter in a veterinary silicone Foley bulb. The bulbs of 45 8-French
      silicone Foley catheters were inflated: 15 with 5 mL of sterile water (SW bulbs),
      15 with 0.9% saline (S bulbs), and 15 with air (A bulbs). The bulbs were
      submerged in 30 mL of synthetic urine in a 50 mL conical tube in a 38 degrees C
      water bath. Five catheters from each group were removed on days 3, 5, and 10 to
      measure bulb volume and diameter. On days 3 and 5, volume and diameter of SW or S
      bulbs were significantly greater than those of A bulbs, but were not
      significantly different from one another. At day 10, only 1 S bulb remained
      intact, 4 of the 5 SW bulbs were intact, the average volume of the SW bulbs was
      2.8 mL, and the A bulbs were all deflated. We conclude that sterile water and
      0.9% saline are both acceptable for Foley bulb inflation of 5 d or less, but
      sterile water might be preferred if bulb inflation must be maintained for more
      than 5 d.

PMID- 22467968
TI  - Surgical correction of an aberrant right subclavian artery in a dog.
AB  - A diagnosis of an aberrant right subclavian artery was made in a 3-month-old
      Boston terrier. Surgical correction was performed after confirming adequate
      collateral circulation. Reports of surgical correction and evaluation of the
      perioperative thoracic limb blood pressure are rare in dogs.

PMID- 22467969
TI  - Pneumomediastinum and subcutaneous emphysema in a cat associated with necrotizing
      bronchopneumonia caused by feline herpesvirus-1.
AB  - This report describes a 1-year-old cat with acute dyspnea. Thoracic radiography
      revealed a pneumomediastinum and severe subcutaneous emphysema. Lower airway
      surgical exploration was unable to determine the cause. At postmortem
      examination, acute necrotizing bronchopneumonia and fibrinonecrotic tracheitis
      due to feline herpesvirus-1 were diagnosed.

PMID- 22467970
TI  - Thoracoscopic correction of a congenital persistent right aortic arch in a young
      cat.
AB  - A 9-week-old kitten was diagnosed with a congenital vascular ring anomaly by
      means of an esophageal contrast study. At 6 mo of age, a non-selective vascular
      study was used to diagnose a persistent right aortic arch (PRAA). Left-sided
      thoracoscopic surgery was performed, using a Liga-Sure vessel sealant device to
      seal and transect the ligamentum arteriosum.

PMID- 22467971
TI  - Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and
      neutropenia mimicking sepsis in a Labrador retriever dog.
AB  - Glucocorticoid-deficient hypoadrenocorticism (GDH) with immune-mediated
      neutropenia (IMN) and -thrombocytopenia (IMT) were diagnosed in a 3-year-old
      Labrador retriever dog. Glucocorticoid-deficient hypoadrenocorticism is rare and
      diagnostically challenging as clinical signs and laboratory abnormalities are
      often nonspecific. Immune-mediated cytopenias and other autoimmune disorders, as
      part of an autoimmune polyglandular syndrome have been reported with
      hypoadrenocorticism in humans. This is the first reported case of
      hypoadrenocorticism and bicytopenia in a dog.

PMID- 22467972
TI  - Periparturient infection with bovine viral diarrhea virus type 1 causes
      hemorrhagic proctocolitis in a cow.
AB  - After 3 cows of a dairy herd had died from severe hemorrhagic diarrhea, a 4th
      sick cow was transported to the clinic. Blood analyses revealed the complete
      absence of white blood cells, the presence of a type 1b strain of bovine viral
      diarrhea virus (BVDV), and seroconversion to BVDV.

PMID- 22467973
TI  - The long journey of cattle plague.

PMID- 22467974
TI  - Half-empty and half-full communication: The client.

PMID- 22467975
TI  - Companion animal client numbers continue to fall in most provinces.

PMID- 22467976
TI  - Evaluation of Laser Ablation Inductively Coupled Plasma Mass Spectrometry for the
      Quantitative Determination of Lead in Different Parts of Archeological Human
      Teeth.
AB  - The lead content of teeth or tooth-parts has been used as a biomarker of
      cumulative lead exposure in clinical, epidemiological, environmental, and
      archaeological studies. Through the application of laser ablation inductively
      coupled plasma mass spectrometry, a pilot study of the micrometer-scale
      distribution and quantification of lead was conducted for two human teeth
      obtained from an archeological burial site in Manhattan, New York, USA. Lead was
      highly localized within each tooth, with accumulation in circumpulpal dentine and
      cementum. The maximum localized lead content in circumpulpal dentine was
      remarkably high, almost 2000 MUg g(-1), compared to the mean enamel and dentine
      content of about 5 MUg g(-1). The maximum lead content in cementum was
      approximately 700 MUg g(-1). The large quantity of cementum found in the teeth
      suggested that the subjects had hypercementosis (excess cementum formation) of
      the root, a condition reported to have been prevalent among African-American
      slave populations. The distribution of lead in these human teeth was remarkably
      similar to the distribution that we previously reported in the teeth of present
      day lead-dosed goats. The data shown demonstrate the feasibility of using laser
      ablation inductively coupled plasma mass spectrometry to examine lead exposure in
      archaeological studies.

PMID- 22467977
TI  - Synthesis of 9-Substituted Xanthenes by the Condensation of Arynes with ortho
      Hydroxychalcones.
AB  - The reaction of o-(trimethylsilyl)aryl triflates, CsF, and o-hydroxychalcones
      affords a general and efficient way to prepare biologically interesting 9
      substituted xanthenes. This chemistry presumably proceeds by tandem
      intermolecular nucleophilic attack of the phenoxide of the chalcone on the aryne
      and subsequent intramolecular Michael addition. The introduction of an external
      base, Cs(2)CO(3), has proven beneficial in this reaction.

PMID- 22467978
TI  - Keep on truckin'.

PMID- 22467979
TI  - Examination of the pharyngeal muscle extracellular matrix offers new clues to
      pathogenesis in obstructive sleep apnea syndrome.

PMID- 22467980
TI  - Heightened awareness in insomnia.

PMID- 22467981
TI  - Altered sleep-related blood pressure profile in hypocretin-deficient narcoleptic
      patients.

PMID- 22467982
TI  - Insufficient sleep and suicidality in adolescents.
AB  - STUDY OBJECTIVES: To investigate the association between the behaviorally induced
      insufficient sleep and suicidality among adolescents. DESIGN: A population-based,
      cross-sectional survey. SETTING: General community. PARTICIPANTS: A sample of
      8,530 students (grades 7-11) was recruited in the Republic of Korea. The
      participants were 8,010 students who completed all questionnaires. INTERVENTION:
      N/A. MEASUREMENTS: The survey included the Beck Scale for Suicidal Ideation
      (SSI), the Beck Depression Inventory (BDI), a modified Epworth Sleepiness Scale
      (ESS), and questionnaires about sleep (weekday/weekend sleep schedule/duration,
      insomnia and snoring). RESULTS: Adolescents with behaviorally induced
      insufficient sleep syndrome (BISS) had higher SSI scores than those who slept >=
      7 hours on weekdays, even after controlling for age, sex, and BDI score (F =
      11.71, P < 0.001). After controlling for age and sex, longer weekend oversleep
      and shorter weekday sleep duration predicted a higher SSI score (beta = 0.19, P <
      0.001; beta = 0.37, P < 0.001). The association between weekend oversleep and SSI
      score remained significant even after additionally controlling for BDI and ESS
      scores and presence of insomnia and snoring (beta = 0.07, P < 0.01). CONCLUSION:
      BISS was found to be associated with increased suicidality. Weekend oversleep was
      associated with suicidality independently of depression, daytime sleepiness,
      snoring, and insomnia. The study findings suggest that chronic sleep restriction
      among adolescents may increase suicidal risk.

PMID- 22467983
TI  - Sleep disordered breathing and depression among U.S. adults: National Health and
      Nutrition Examination Survey, 2005-2008.
AB  - STUDY OBJECTIVE: To determine if symptoms of sleep disordered breathing (SDB) are
      associated with depression symptomology in a national sample. DESIGN: National
      Health and Nutrition Examination Survey. SETTING: U.S., 2005-2008. PARTICIPANTS:
      9,714 adults (>= 18 years). MEASUREMENTS: Respondents were asked about frequency
      of snoring and snorting, gasping, or stopping breathing while asleep and
      completed the PHQ-9 (a 9-item depression screener). Odds ratios (OR) and 95%
      confidence intervals (CI) for SDB symptom-associated probable major depression
      (defined as a PHQ-9 score >= 10) were obtained from sex-specific logistic
      regression analyses adjusted for body mass index, age, race/ethnicity, and
      education. RESULTS: Among men, 6.0% reported physician-diagnosed sleep apnea,
      37.2% snored >= 5 nights/week, 7.1% snorted/stopped breathing >= 5 nights/week,
      and 5.0% had PHQ-9 scores >= 10. Among women, 3.1% reported sleep apnea, 22.4%
      snored >= 5 nights/week, 4.3% snorted/stopped breathing >= 5 nights/week, and
      8.4% had PHQ-9 scores >= 10. Sleep apnea was associated with probable major
      depression (OR = 2.4; 95% CI: 1.5, 3.6 among men; OR = 5.2; 95% CI: 2.7, 9.9
      among women). Snoring was not associated with depression symptoms in men or
      women. Snorting/stopping breathing >= 5 nights/week compared to never was
      strongly associated with probable major depression in men (OR = 3.1; 95% CI: 1.8,
      5.2) and women (OR = 3.0; 95% CI: 1.6, 5.4). CONCLUSION: Frequent
      snorting/stopping breathing was associated with probable major depression by the
      PHQ-9 in a national sample of adults. Additional research may be needed to
      determine whether regular screening for these conditions by mental health
      professionals and sleep specialists should be recommended.

PMID- 22467984
TI  - Assessing sleepiness and sleep disorders in Australian long-distance commercial
      vehicle drivers: self-report versus an "at home" monitoring device.
AB  - STUDY OBJECTIVES: As obstructive sleep apnea (OSA) is associated with a higher
      risk of motor vehicle crashes, there is increasing regulatory interest in the
      identification of commercial motor vehicle (CMV) drivers with this condition.
      This study aimed to determine the relationship between subjective versus
      objective assessment of OSA in CMV drivers. DESIGN: Cross-sectional survey.
      SETTINGS: Heavy vehicle truck stops located across the road network of 2 large
      Australian states. PARTICIPANTS: A random sample of long distance commercial
      vehicle drivers (n = 517). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Drivers
      were interviewed regarding their driving experience, personal health, shift
      schedules, payments, and various questions on sleep and tiredness in order to
      describe their sleep health across a range of variables. In addition, home
      recordings using a flow monitor were used during one night of sleep. Only 4.4% of
      drivers reported a previous diagnosis of sleep apnea, while our at home
      diagnostic test found a further 41% of long-distance heavy vehicle drivers likely
      to have sleep apnea. The multivariable apnea prediction index, based on self
      report measures, showed poor agreement with the home-monitor detected sleep apnea
      (AUC 0.58, 95%CI = 0.49-0.62), and only 12% of drivers reported daytime
      sleepiness (Epworth Sleepiness Scale score > 10). Thirty-six percent of drivers
      were overweight and a further 50% obese; 49% of drivers were cigarette smokers.
      CONCLUSIONS: Sleep apnea remains a significant and unrecognized problem in CMV
      drivers, who we found to have multiple health risks. Objective testing for this
      sleep disorder needs to be considered, as symptom reports and self-identification
      appear insufficient to accurately identify those at risk.

PMID- 22467985
TI  - The impact of a telemedicine monitoring system on positive airway pressure
      adherence in patients with obstructive sleep apnea: a randomized controlled
      trial.
AB  - STUDY OBJECTIVES: First-line therapy for patients with moderate to severe
      obstructive sleep apnea (OSA) is positive airway pressure (PAP). Although PAP is
      a highly efficacious treatment, adherence to PAP is still a substantial clinical
      problem. The objective of this study was to determine whether PAP adherence can
      be improved with a telemedicine monitoring system. DESIGN: A nonblinded, single
      center, randomized controlled trial that compared standard PAP treatment versus
      PAP treatment and a telemedicine monitoring system SETTING: University sleep
      disorders program in British Columbia, Canada PATIENTS: Adult patients (>= 19 yr
      of age) with moderate to severe OSA (apnea hypopnea index (AHI) >= 15 events/hr
      determined by polysomnography) prescribed PAP INTERVENTIONS: Patients were
      randomized to either standard care with an autotitrating PAP machine or an
      autotitrating PAP machine that transmitted physiologic information (i.e.,
      adherence, air leak, residual AHI) daily to a website that could be reviewed. If
      problems were identified from information from the website, the patient was
      contacted by telephone as necessary. MEASUREMENTS: PAP adherence after 3 mo,
      subjective sleep quality, and side effects RESULTS: Seventy-five patients were
      enrolled; 39 were randomized to telemedicine and 36 to standard care. The mean
      age +/- standard deviation (SD) was 53.5 +/- 11.2 yr, mean AHI was 41.6 +/- 22.1
      events/hr, and 80% of patients were male. After 3 mo, mean PAP adherence was
      significantly greater in the telemedicine arm (191 min per day) versus the
      standard arm (105 min per day; mean difference = 87 min, 95% confidence interval
      (CI): 25-148 min, P = 0.006, unpaired t test). On days when PAP was used, mean
      adherence was 321 min in the telemedicine arm and 207 min in the standard arm
      (difference = 113 min, 95% CI: 62-164 min, P < 0.0001). Significant independent
      predictors of adherence included age, baseline Epworth Sleepiness Scale score,
      and use of telemedicine. On average, an additional 67 min of technician time was
      spent on patients in the telemedicine arm compared with the standard arm (P =
      0.0001). CONCLUSIONS: PAP adherence can be improved with the use of a web-based
      telemedicine system at the initiation of treatment.

PMID- 22467986
TI  - The extracellular matrix of the lateral pharyngeal wall in obstructive sleep
      apnea.
AB  - STUDY OBJECTIVES: To compare the components of the extracellular matrix in the
      lateral pharyngeal muscular wall in patients with and without obstructive sleep
      apnea (OSA). This may help to explain the origin of the increased collapsibility
      of the pharynx in patients with OSA. DESIGN: Specimens from the superior
      pharyngeal constrictor muscle, obtained during pharyngeal surgeries, were
      evaluated using histochemical and immunohistochemical analyses to determine the
      fractional area of collagen types I and III, elastic fibers, versican,
      fibronectin, and matrix metalloproteinases 1 and 2 in the endomysium. SETTING:
      Academic tertiary center. PATIENS: A total of 51 nonobese adult patients, divided
      into 38 patients with OSA and 13 nonsnoring control subjects without OSA.
      INTERVENTIONS: Postintervention study performed on tissues from patients after
      elective surgery. MEASUREMENTS AND RESULTS: Pharyngeal muscles of patients with
      OSA had significantly more collagen type I than pharyngeal muscles in control
      subjects. Collagen type I was correlated positively and independently with age.
      The other tested components of the extracellular matrix did not differ
      significantly between groups. In a logistic regression, an additive effect of
      both the increase of collagen type I and the increase in age with the presence of
      OSA was observed (odds ratio (OR), 2.06; 95% confidence interval (CI), 1.17
      3.63), when compared with the effect of increased age alone (OR, 1.11; 95% CI,
      1.03-1.20). CONCLUSION: Collagen type I in the superior pharyngeal constrictor
      muscle was more prevalent in patients with OSA and also increased with age. It
      was hypothesized that this increase could delay contractile-relaxant responses in
      the superior pharyngeal constrictor muscle at the expiratory-inspiratory phase
      transition, thus increasing pharyngeal collapsibility.

PMID- 22467987
TI  - Sleep quality and 1-year incident cognitive impairment in community-dwelling
      older adults.
AB  - STUDY OBJECTIVES: To examine in cognitively intact older men and women the
      associations between subjective sleep quality and 1-yr incident cognitive
      impairment. DESIGN: Prospective cohort study. SETTING: General community.
      PARTICIPANTS: 1,664 cognitively intact individuals age 65 to 96 years.
      MEASUREMENTS AND RESULTS: Sleep quality at baseline was measured using the
      Pittsburgh Sleep Quality Index (PSQI). Cognitive functioning was assessed at
      baseline and 12 months later using the Mini-Mental State Examination (MMSE).
      Incident general cognitive impairment was defined according to a follow-up MMSE
      score below the 15(th) percentile according to normative data and of at least 2
      points below baseline. General cognitive impairments were also separated into
      amnestic and nonamnestic subtypes according to MMSE delayed recall performance.
      Associations between sleep quality indicators at baseline and incident cognitive
      impairment were assessed by odds ratio (OR) adjusted for age, education, baseline
      MMSE score, psychotropic drug use, anxiety, depressive episodes, cardiovascular
      conditions, and chronic diseases. Results revealed that global PSQI score was
      significantly linked with incident cognitive impairment (OR 1.17, 95% confidence
      interval (CI) 1.05-1.30) in men, but not in women. In women, sleep disturbance
      score (OR 2.62, 95% CI 1.41-4.86) and long sleep duration (>= 9 hr; OR 3.70, 95%
      CI 1.49-9.17) were associated with nonamnestic and amnestic incident cognitive
      impairment, respectively. In men, short sleep duration (<= 5 hr; OR 4.95, 95% CI
      1.72-14.27) and habitual sleep efficiency score (OR 1.94, 95% CI 1.42-2.66) were
      associated with amnestic and general incident cognitive impairment, respectively.
      CONCLUSIONS: Sleep quality in older adults should receive particular attention by
      clinicians because poor sleep quality can be an early sign of cognitive decline.

PMID- 22467988
TI  - Enhanced frontoparietal synchronized activation during the wake-sleep transition
      in patients with primary insomnia.
AB  - INTRODUCTION: Cognitive and brain hyperactivation have been associated with
      trouble falling asleep and sleep misperception in patients with primary insomnia
      (PI). Activation and synchronization/temporal coupling in frontal and
      frontoparietal regions involved in executive control and endogenous attention
      might be implicated in these symptoms. METHODS: Standard polysomnography (PSG)
      and electroencephalogram (EEG) were recorded in 10 unmedicated young patients
      (age 19-34 yr) with PI with no other sleep/medical condition, and in 10 matched
      control subjects. Absolute power, temporal coupling, and topographic source
      distribution (variable resolution electromagnetic tomography or VARETA) were
      obtained for all time spent in waking, Stage 1 and Stage 2 of the wake-sleep
      transition period (WSTP), and the first 3 consecutive min of N3. Subjective sleep
      quality and continuity were evaluated. RESULTS: In comparison with control
      subjects, patients with PI exhibited significantly higher frontal beta power and
      current density, and beta and gamma frontoparietal temporal coupling during
      waking and Stage 1. CONCLUSION: These findings suggest that frontal deactivation
      and disengagement of brain regions involved in executive control, attention, and
      self-awareness are impaired in patients with PI. The persistence of this
      activated and coherent network during the wake-sleep transition period (WSTP) may
      contribute to a better understanding of underlying mechanisms involved in
      difficulty in falling asleep, in sleep misperception, and in the lighter, poorer,
      and nonrefreshing sleep experienced by some patients with PI.

PMID- 22467989
TI  - Ambient temperature and obstructive sleep apnea: effects on sleep, sleep apnea,
      and morning alertness.
AB  - STUDY OBJECTIVES: The aim of the study was to investigate the effect of ambient
      temperature on sleep, sleep apnea, and morning alertness in patients with
      obstructive sleep apnea. DESIGN: Randomized controlled trial. SETTING: In
      hospital investigations. PARTICIPANTS: Forty patients with obstructive sleep
      apnea naive to treatment, with an apnea-hypopnea index of 10-30. INTERVENTIONS:
      Three different nights in room temperatures of 16 degrees C, 20 degrees C, and 24
      degrees C. MEASUREMENTS: Overnight polysomnography and Karolinska Sleepiness
      Scale. RESULTS: The obstructive apnea-hypopnea index was 30 +/- 17 at 16 degrees
      C room temperature, 28 +/- 17 at 20 degrees C, and 24 +/- 18 at 24 degrees C. The
      obstructive apnea-hypopnea index was higher at 16 degrees C room temperature
      versus 24 degrees C (P = 0.001) and at 20 degrees C room temperature versus 24
      degrees C (P = 0.033). Total sleep time was a mean of 30 min longer (P = 0.009),
      mean sleep efficiency was higher (77 +/- 11% versus 71 +/- 13% respectively, P =
      0.012), and the patients were significantly more alert according to the
      Karolinska Sleepiness Scale (P < 0.028) in the morning at 16 degrees C room
      temperature versus 24 degrees C. The amount of sleep in different sleep stages
      was not affected by room temperature. CONCLUSIONS: Untreated patients with
      obstructive sleep apnea sleep longer, have better sleep efficiency, and are more
      alert in the morning after a night's sleep at 16 degrees C room temperature
      compared with 24 degrees C, but obstructive sleep apnea is more severe at 16
      degrees C and 20 degrees C compared with 24 degrees C. CLINICAL TRIAL
      INFORMATION: This study is registered in ClinicalTrials.gov number NCT00544752.

PMID- 22467990
TI  - Abnormal sleep-cardiovascular system interaction in narcolepsy with cataplexy:
      effects of hypocretin deficiency in humans.
AB  - STUDY OBJECTIVE: Narcolepsy with cataplexy (NC) is associated with loss of
      hypocretin neurons in the lateral hypothalamus involved in the circadian timing
      of sleep and wakefulness, and many biologic functions including autonomic
      control. The authors investigated whether chronic lack of hypocretin signaling
      alters cardiovascular control during sleep in humans. DESIGN: Comparison of 24-hr
      circadian rhythms, day-night, time- and state-dependent changes of blood pressure
      (BP) and heart rate (HR) in drug-free patients with NC and control subjects.
      SETTING: University hospital. PATIENTS OR PARTICIPANTS: Ten drug-free patients
      with NC (9 men, 1 woman) and 12 control subjects (9 men, 3 women). INTERVENTIONS:
      N/A. MEASUREMENTS AND RESULTS: Daytime BP was comparable in patients with NC and
      controls, but patients with NC displayed a nighttime nondipping BP pattern. The
      24-hr circadian rhythmicity of BP and HR was normal in both groups. Systolic BP
      during nighttime rapid eye movement sleep was significantly increased in the NC
      group. The 24-hr HR was significantly higher in the NC group but the day-night
      and state-dependent HR modulations were intact. The nighttime BP pattern coupled
      in the NC group with increased sleep fragmentation and a higher prevalence of
      arousals, periodic limb movements in sleep (PLMS), and PLMS arousals. In an
      analysis of the sleep/cardiovascular interaction in the periods after sleep onset
      and preceding morning awakening, only PLMS were consistently associated with the
      blunted nighttime decrease in BP in the NC group. CONCLUSIONS: Hypocretin
      deficiency in humans may couple with an altered nighttime BP regulation that can
      be associated with an increased cardiovascular risk. This finding may be the
      result not only of the hypocretinergic deficiency per se but also of the altered
      sleep/wake regulation characterizing NC.

PMID- 22467991
TI  - Sleep bruxism is associated with a rise in arterial blood pressure.
AB  - STUDY OBJECTIVES: Sleep bruxism (SB) is a movement disorder identified by
      grinding of teeth and rhythmic masticatory muscle activity (RMMA). RMMA is
      associated with body movements and cortical arousals. Increases in autonomic
      sympathetic activities that characterize sleep cortical arousal precede RMMA/SB.
      Based on these findings, this study examined whether RMMA/SB episodes are also
      associated with significant changes in arterial blood pressure (BP). DESIGN:
      Participants underwent 3 nights of full polysomnography that included noninvasive
      beat-to-beat BP recording. Single RMMA/SB episodes and arousal episodes were
      analyzed in stage 2 sleep and categorized as: (i) RMMA/SB + arousal; (ii) RMMA/SB
      + body movement; (iii) RMMA/SB + arousal + body movement; or (iv) arousal alone.
      Sleep and RMMA/SB data were compared to a Non SB group. RMMA/SB clusters (RMMA/SB
      episodes <= 30 sec apart) were also analyzed. SETTING: Sleep Laboratory at
      l'Hopital du Sacre-Coeur de Montreal. PARTICIPANTS: Ten young, healthy
      participants with SB (mean age = 26 +/- 1.8 years) and 9 without SB (mean age =
      29 +/- 1.2 years). INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: BP increased with
      all RMMA/SB and arousal episodes (P <= 0.05). The average maximum BP surges
      (systolic/diastolic +/- SE mm Hg) were: 25.6 +/- 3.3/12.6 +/- 2.0 for RMMA/SB +
      arousal; 30.1 +/- 1.7/19.1 +/- 1.9 for RMMA/SB + body movement; 26.0 +/- 2.8/15.1
      +/- 2.0 for RMMA/SB + arousal + body movement; 19.4 +/- 2.3/8.9 +/- 1.2 for
      arousal alone; and for RMMA/SB clusters: Episode: 1: 26.2 +/- 8.7/16.4 +/- 5.7;
      Episode 2: 21.1 +/- 7.9/12.6 +/- 6.4. CONCLUSION: Rhythmic masticatory muscle
      activity/sleep bruxism (RMMA/SB) is associated with blood pressure fluctuations
      during sleep. Arousals and body movements often occur with RMMA/SB and can impact
      the magnitude of this BP surge.

PMID- 22467992
TI  - Sleep loss exacerbates fatigue, depression, and pain in rheumatoid arthritis.
AB  - STUDY OBJECTIVES: Disturbances of sleep are hypothesized to contribute to pain.
      However, experimental data are limited to healthy pain-free individuals. This
      study evaluated the effect of sleep loss during part of the night on daytime mood
      symptoms and pain perceptions in patients with rheumatoid arthritis in comparison
      with control subjects. DESIGN: A between-groups laboratory study with assessment
      of mood symptoms and pain perception before and after partial night sleep
      deprivation (PSD; awake 23:00 hr to 03:00 hr). SETTING: General clinical research
      center. PARTICIPANTS: Patients with rheumatoid arthritis (n = 27) and volunteer
      comparison control subjects (n = 27). MEASUREMENTS: Subjective reports of sleep,
      mood symptoms and pain, polysomnographic assessment of sleep continuity, and
      subjective and objective assessment of rheumatoid arthritis-specific joint pain.
      RESULTS: PSD induced differential increases in self-reported fatigue (P < 0.09),
      depression (P < 0.04), anxiety (P < 0.04), and pain (P < 0.01) in patients with
      rheumatoid arthritis compared with responses in control subjects, in whom
      differential increases of self-reported pain were independent of changes in mood
      symptoms, subjective sleep quality, and objective measures of sleep
      fragmentation. In the patients with rheumatoid arthritis, PSD also induced
      increases in disease-specific activity as indexed by self-reported pain severity
      (P < 0.01) and number of painful joints (P < 0.02) as well as clinician-rated
      joint counts (P < 0.03). CONCLUSION: This study provides the first evidence of an
      exaggerated increase in symptoms of mood and pain in patients with rheumatoid
      arthritis after sleep loss, along with an activation of rheumatoid arthritis
      related joint pain. Given the reciprocal relationship between sleep disturbances
      and pain, clinical management of pain in patients with rheumatoid arthritis
      should include an increased focus on the prevention and treatment of sleep
      disturbance in this clinical population.

PMID- 22467993
TI  - Genetic background has a major impact on differences in sleep resulting from
      environmental influences in Drosophila.
AB  - STUDY OBJECTIVES: To determine the effect of different genetic backgrounds on
      demographic and environmental interventions that affect sleep and evaluate
      variance of these measures; and to evaluate sleep and variance of sleep behaviors
      in 6 divergent laboratory strains of common origin. DESIGN: Assessment of the
      effects of age, sex, mating status, food sources, and social experience using
      video analysis of sleep behavior in 2 different strains of Drosophila,
      white(1118ex) (w(1118ex)) and white Canton-S (w(CS10)). Sleep was also determined
      for 6 laboratory strains of Canton-S and 3 inbred lines. The variance of total
      sleep was determined for all groups and conditions. MEASUREMENTS AND RESULTS: The
      circadian periods and the effects of age upon sleep were the same between
      w(1118ex) and w(CS10) strains. However, the w(1118ex) and w(CS10) strains
      demonstrated genotype-dependent differences in the effects upon sleep of sex,
      mating status, social experience, and being on different foods. Variance of total
      sleep was found to differ in a genotype dependent manner for interventions
      between the w(1118ex) and w(CS10) strains. Six different laboratory Canton-S
      strains were found to have significantly different circadian periods (P < 0.001)
      and sleep phenotypes (P < 0.001). Three inbred lines showed reduced variance for
      sleep measurements. CONCLUSIONS: One must control environmental conditions in a
      rigorously consistent manner to ensure that sleep data may be compared between
      experiments. Genetic background has a significant impact upon changes in sleep
      behavior and variance of behavior due to demographic factors and environmental
      interventions. This represents an opportunity to discover new genes that modify
      sleep/wake behavior.

PMID- 22467994
TI  - Using repeated measures of sleep disturbances to predict future diagnosis
      specific work disability: a cohort study.
AB  - CONTEXT: It is unknown whether or not measuring sleep disturbances repeatedly,
      rather than at only one point in time, improves prediction of work disability.
      STUDY OBJECTIVE: o examine sleep disturbance patterns over time as a risk marker
      for diagnosis-specific work disability. DESIGN: Prospective cohort study linking
      repeatedly measured self-reported sleep disturbances with records of physician
      certified work disability (sickness absence) from a national register.
      Participants responded to surveys in 2000-2002, and 2004, and were followed up
      for 12 mo. SETTING: Public sector employees in Finland. PARTICIPANTS: 25,639
      participants (mean age 45.6 yr, 82% female). MAIN OUTCOME MEASURE: Incident
      diagnosis-specific sickness absence of > 9 days. RESULTS: During a mean follow-up
      of 323 days, 4,975 employees (19%) had a new episode of sickness absence. In
      multivariable-adjusted models corrected for multiple testing, stable severe sleep
      disturbances, in comparison with no sleep disturbances, were associated with an
      increased risk of sickness absence due to diseases of the musculoskeletal system
      (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.45-1.95), and injuries
      and poisonings (HR 1.64, 95% CI 1.23-2.18). Increases in sleep disturbances
      predicted subsequent sickness absence due to mental disorders (HR 1.59, 95% CI
      1.32-1.91), and diseases of the musculoskeletal system (HR 1.44, 95% CI 1.27
      1.64) According to net reclassification improvement analyses, measurement of
      sleep disturbance patterns rather than the level of sleep disturbances at one
      point in time improved prediction of all-cause sickness absence by 14%, and
      diagnosis-specific sickness absences up to 17% (P for improvement < 0.001).
      CONCLUSIONS: Increasing and severe chronic sleep disturbances mark an increased
      risk of diagnosis-specific work disability.

PMID- 22467995
TI  - PER3 polymorphism and insomnia severity in alcohol dependence.
AB  - STUDY OBJECTIVES: Insomnia is common, persistent, and associated with relapse in
      alcohol-dependent (AD) patients. Although the underlying mechanisms are mostly
      unstudied, AD patients have impaired circadian rhythms and sleep drive, which may
      be genetically influenced. A polymorphism in the PER3 gene (PER3(4/4), PER3(4/5),
      PER3(5/5)) has previously been associated with circadian preference and sleep
      homeostasis, and the PER3(4/4)genotype has been characterized by evening
      preference and decreased sleep drive. The purpose of this study was to examine
      the influence of this polymorphism on insomnia severity in AD patients. We
      hypothesized that the PER3 polymorphism would be an independent predictor of
      insomnia severity with greatest severity observed in those with the
      PER3(4/4)genotype. DESIGN: Cross-sectional association of patient
      characteristics, genotype, and insomnia severity. Significant (P < 0.05)
      bivariate correlates were further analyzed by hierarchical, forced entry multiple
      linear regression. SETTING: Alcohol treatment programs in Warsaw, Poland.
      PATIENTS: Diagnosed with alcohol dependence (n = 285), according to the
      Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition.
      MEASUREMENTS AND RESULTS: Drinking frequency, mental and physical health status,
      childhood abuse, and PER3 genotype were independent predictors of insomnia
      severity, as measured by a 7-item subscale of the Sleep Disorders Questionnaire,
      explaining 28.9% of the variance. Addition of the genotype in the final step
      significantly increased the amount of variance explained by 1.1% (P = 0.027).
      Those with the PER3(4/4)genotype had the greatest severity of insomnia symptoms.
      CONCLUSIONS: PER3 genotype contributed unique variance in predicting insomnia
      severity in AD patients. These results are consistent with genetically influenced
      impairment in sleep regulation mechanisms in AD patients with insomnia.

PMID- 22467996
TI  - Maternal insomnia and children's family socialization environments.
AB  - STUDY OBJECTIVES: To examine concurrent associations between maternal insomnia
      and different aspects of the family socialization environment. DESIGN: Mothers
      reported on their symptoms of insomnia in a private standardized interview and
      interviewers evaluated the family socialization environment using the Coder's
      Inventory. SETTING: Assessments were conducted in participants' homes within the
      U.K. PATIENTS OR PARTICIPANTS: One thousand one hundred sixteen mothers of
      British children enrolled in the Environmental Risk (E-Risk) study were invited
      to participate when their children were aged 12 years. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: After controlling for family socioeconomic status
      (SES), mothers' relationship status, and maternal depression, maternal insomnia
      was associated with a poorer family socialization environment (beta = -0.10, [95%
      confidence intervals (CI) = -0.16, -0.04], P < 0.001). When family socialization
      environment subscales were examined, after controlling for family SES, mothers'
      relationship status, and maternal depression, maternal insomnia was associated
      with greater chaos (beta = 0.09, [95% CI = 0.03, 0.15], P = 0.002), greater child
      neglect (beta = 0.13, [95% CI = 0.07, 0.18], P < 0.001), less happiness (beta = 
      0.13, [95% CI = -0.18, -0.07], P < 0.001), less child stimulation (beta = -0.06,
      [95% CI = -0.11, 0.00], P = 0.043), but not poorer state of the home, such as
      orderliness (beta = -0.04, [95% CI = -0.10, 0.02], P = 0.182). CONCLUSIONS:
      Maternal insomnia is associated with the family socialization environment. This
      finding emphasizes the need to consider insomnia in the family context.

PMID- 22467997
TI  - Correcting for Population Stratification in Genomewide Association Studies.
AB  - Genomewide association studies have become the primary tool for discovering the
      genetic basis of complex human diseases. Such studies are susceptible to the
      confounding effects of population stratification, in that the combination of
      allele-frequency heterogeneity with disease-risk heterogeneity among different
      ancestral subpopulations can induce spurious associations between genetic
      variants and disease. This article provides a statistically rigorous and
      computationally feasible solution to this challenging problem of unmeasured
      confounders. We show that the odds ratio of disease with a genetic variant is
      identifiable if and only if the genotype is independent of the unknown population
      substructure conditional on a set of observed ancestry-informative markers in the
      disease-free population. Under this condition, the odds ratio of interest can be
      estimated by fitting a semiparametric logistic regression model with an arbitrary
      function of a propensity score relating the genotype probability to ancestry
      informative markers. Approximating the unknown function of the propensity score
      by B-splines, we derive a consistent and asymptotically normal estimator for the
      odds ratio of interest with a consistent variance estimator. Simulation studies
      demonstrate that the proposed inference procedures perform well in realistic
      settings. An application to the well-known Wellcome Trust Case-Control Study is
      presented. Supplemental materials are available online.

PMID- 22467998
TI  - Behavioral, Ecological, and Evolutionary Aspects of Meat-Eating by Sumatran
      Orangutans (Pongo abelii).
AB  - Meat-eating is an important aspect of human evolution, but how meat became a
      substantial component of the human diet is still poorly understood. Meat-eating
      in our closest relatives, the great apes, may provide insight into the emergence
      of this trait, but most existing data are for chimpanzees. We report 3 rare cases
      of meat-eating of slow lorises, Nycticebus coucang, by 1 Sumatran orangutan
      mother-infant dyad in Ketambe, Indonesia, to examine how orangutans find slow
      lorises and share meat. We combine these 3 cases with 2 previous ones to test the
      hypothesis that slow loris captures by orangutans are seasonal and dependent on
      fruit availability. We also provide the first (to our knowledge) quantitative
      data and high-definition video recordings of meat chewing rates by great apes,
      which we use to estimate the minimum time necessary for a female Australopithecus
      africanus to reach its daily energy requirements when feeding partially on raw
      meat. Captures seemed to be opportunistic but orangutans may have used olfactory
      cues to detect the prey. The mother often rejected meat sharing requests and only
      the infant initiated meat sharing. Slow loris captures occurred only during low
      ripe fruit availability, suggesting that meat may represent a filler fallback
      food for orangutans. Orangutans ate meat more than twice as slowly as chimpanzees
      (Pan troglodytes), suggesting that group living may function as a meat intake
      accelerator in hominoids. Using orangutan data as a model, time spent chewing per
      day would not require an excessive amount of time for our social ancestors
      (australopithecines and hominids), as long as meat represented no more than a
      quarter of their diet. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of
      this article (doi:10.1007/s10764-011-9574-z) contains supplementary material,
      which is available to authorized users.

PMID- 22467999
TI  - Remnant B-cell-stimulative and anti-oxidative effects of Persea americana fruit
      extract studied in rats introduced into streptozotocin - induced hyperglycaemic
      state.
AB  - Insulin-stimulative and anti-oxidative effects of Persea americana fruit extract
      were evaluated using streptozotocin (STZ). Ethanol extract of P. americana in the
      concentration of 300 mg/kg body weight/rat /day was orally administered to rats
      introduced into STZ-induced hyperglycaemic state for a period of 30 days. After
      the treatment with avocado fruit extract, the elevated levels of blood glucose,
      glycosylated haemoglobin, blood urea and serum creatinine seen in the
      hyperglycaemic rats, reverted back to near normal. Similarly, significantly
      decreased plasma insulin and haemoglobin levels went back to near normal after
      the treatment, suggesting the insulin-stimulative effect of P. americana fruit.
      Determination of thiobarbituric acid reactive substances (TBARS), hydroperoxides
      and both enzymatic and non-enzymatic antioxidants, confirmed the anti-oxidative
      potential of avocado fruit extract which, in turn, might be responsible for its
      hypoglycaemic potential. Changes in activities of enzymes such as serum aspartate
      transaminase (AST), serum alanine transaminase (ALT), and serum alkaline
      phosphatase (ALP) seen in the control and experimental rats, revealed the tissue
      protective nature of Persea americana fruits, while all of the analysed
      biochemical parameters were comparable to those obtained with gliclazide as a
      standard reference drug.

PMID- 22468000
TI  - Wound healing potential of methanol extract of Spathodea campanulata stem bark
      formulated into a topical preparation.
AB  - This study evaluated the wound healing potential of Spathodea campanulata stem
      bark in Sprague Dawley rats using the excision wound model. The methanol extract
      contained glycosides, flavonoids and tannins, and was relatively stable when
      stored at the room temperature for six (6) months. Solvent-free, semi-solid
      extract of S. campanulata was incorporated into an aqueous cream and applied (10
      % w/w and 20 % w/w) on excision wounds of thirty two (32) rats. Cicatrin((r))
      cream was used as a standard wound healing agent. Prior to the remedial cream
      application, done later on twice daily, sixteen (16) rats had their wounds
      infected with Staphylococcus aureus, while in the remaining sixteen the wounds
      were kept clean. The surface area of the excision wounds was monitored
      planimetrically every four (4) days until a complete wound closure or healing
      took place. Excision wounds treated with 20 % w/w Spathodea cream and
      Cicatrin((r)) cream showed a rapid and comparable decrease (p > 0.05) in wound
      size. In uninfected wounds, both 20 % w/w Spathodea cream and Cicatrin((r)) cream
      application resulted in ~ 95 %-wound closure seen on Day 20, and a complete
      closure seen on Day 24. In infected wounds, both 20 % w/w Spathodea cream and
      Cicatrin((r)) cream administration led to ~ 91 %-wound closure on Day 24 and a
      complete wound contraction on Day 28. The results of this study justify the
      folkloric use of S. campanulata stem bark to the effect of wound treatment.

PMID- 22468001
TI  - Effects of Chinese Materia Medica-Fubao Danggui Jiao on experimental
      endometriosis.
AB  - The objective of this paper was to investigate the effects of a Chinese Materia
      Medica variant -Fubao Danggui Jiao (FDJ)-on experimental endometriosis. An
      endometriosis model was created by virtue of auto-transplantation of endometrial
      tissue onto rats' abdominal walls. The implants were allowed to grow for 30 days
      until the successful completion of the model. After that, forty endometriotic
      rats were randomly divided into four study groups and given different treatments:
      (1) negative control group (water, 2ml/kg, per os); (2) FDJ-A group (FDJ, 2ml/kg,
      per os); (3) FDJ-B group (FDJ, 4ml/kg, per os); (4) Danazol group (70mg/kg, per
      os). After 30 days with treatments, the volumes of endometriotic implants in each
      rat were measured. The implants and normal uterine horns were removed for routine
      histological examination. FDJ caused significant decreases in volumes of the
      surviving endometriotic implants, with two different doses having statistically
      equivalent effects. Upon histological examination, FDJ was observed to cause
      regression of epithelium and stroma of endometriotic implants. FDJ had revealed
      promising therapeutic effects on endometriosis.

PMID- 22468002
TI  - Neuropharmacological effects of Nigerian honey in mice.
AB  - Honey is a natural sweet substance that bees produce by transforming flower
      nectar or other sweet secretions of plants. It has widespread use in traditional
      medicine in various parts of the world. It has been reported to assist in
      building the entire central nervous system. The beneficial effects of honey have
      been attributed to the possible polyphenolic contents and some other
      constituents. The geographical locations and the sources of plant nectars may
      contribute to the effects of honey samples. Thus, we evaluated the
      neuropharmacological effects of six samples of honey (10%, 20% and 40%(V)/v,
      p.o.) from three geographical locations of Nigeria using the following behavioral
      models: Novelty-induced behaviors (NIB), learning and memory, pentobarbital
      induced hypnosis, anxiolytic, anticonvulsant, analgesic and antidepressant models
      in mice. The results showed that honey significantly (p< 0.05) decreased
      locomotion and rearing behaviors in NIB and amphetamine-induced locomotor
      activity when compared to the control group. Exploratory behavior was
      significantly increased in both holeboard and elevated plus maze but had no
      significant effect on spatial working memory. Honey sample from Umudike has
      significant hypnotic and anticonvulsant effects. The antinociceptive models (hot
      plate and tail flick tests) showed that the honey samples significantly increased
      the pain reaction time and naloxone blocked these central antinociceptive
      effects. The force swimming test showed that only the Idanre (ID) honey sample
      had antidepressant effect. In conclusion, some of these honey samples have
      central inhibitory property, anxiolytic, antinociceptive, anticonvulsant and
      antidepressant effects, thus may be used as nutraceutic. It can also be inferred
      that some of these effects are probably mediated through dopaminergic and
      opioidergic systems.

PMID- 22468003
TI  - Formulation and characterization of modified release tablets containing isoniazid
      using swellable polymers.
AB  - The aim of this work was to develop swellable modified release (MR) isoniazid
      tablets using different combinations of polyvinyl acetate (PVAc) and sodium
      carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation
      technique and then compressed into tablets. In vitro release studies for 12 hr
      were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and
      7.5. Tablets of all formulations were found to be of good physical quality with
      respect to appearance (width and thickness), content uniformity, hardness, weight
      variation and friability. In vitro release data showed that increasing total
      polymer content resulted in more retarding effect. Formulation with 35% polymer
      content exhibited zero order release profile and it released 35% of the drug in
      first hr, later on, controlled drug release was observed upto the 12(th) hour.
      Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern
      at levels of studied concentrations, which suggested that this combination can be
      used to formulate zero order release tablets of water soluble drugs like
      isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian
      transport is the primary mechanism of isoniazid release from PVAc and Na-CMC
      based tablets. The value of mean dissolution time decreased with the increase in
      the release rate of drug clearly showing the retarding behavior of the swellable
      polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may
      be feasible to formulate zero order release tablets of water soluble drugs like
      isoniazid.

PMID- 22468004
TI  - Neuropharmacological profile of aqueous extract of Anaphe venata larva
      (Notondotidae) in rats.
AB  - Consumption of Anaphe larva had been reported to cause seasonal ataxia and
      impaired consciousness. Therefore this study examined the neuropharmacological
      and mechanism(s) of action of aqueous extract of Anaphe venata in rats.
      Behavioural effects namely rearing, stretching, sniffing and ataxia were
      determined after the intraperitoneal administration of aqueous extract of Anaphe
      larva in rats. Animals were divided into groups and graded doses (100, 200 and
      400 mg/kg, i.p.) of extract were administered. The control group was administered
      normal saline (vehicle). The effects of scopolamine (3 mg/kg, i.p.), flumazenil
      (2 mg/kg, i.p.), naloxone (2.5 mg/kg, i.p.), and thiamine (1 mg/kg, i.p.) on the
      observed behavioral changes were also examined. The effects of the extract
      administered intraperitoneally at a dose of 200 mg/kg on the amphetamine-induced
      stereotypy and locomotion were evaluated. Aqueous anaphe extract induced
      significant (p< 0.01) stretching and ataxia behavioural effects while it
      inhibited rearing behaviour when compared with the vehicle-treated group.
      However, it had no significant effect on sniffing behaviour. Scopolamine reversed
      all the effects of the extract on rearing, stretching and ataxia. Both Flumazenil
      and naloxone only reversed the effects of the extract on stretching and ataxia
      induced behaviours significantly. However, thiamine potentiated both stretching
      and ataxia-induced behaviours. The extract inhibited the amphetamine-induced
      stereotype behaviour and locomotion. In conclusion, these results showed that
      these anaphe-induced behavioural effects are mediated via cholinergic, GABAergic,
      opioidergic and dopaminergic receptor systems with strong muscarinic-cholinergic
      receptors involvement in ataxia-induced behaviour. We therefore suggest that
      muscranic-cholinergic like drugs may be of benefit in the management of patients
      that present with clinical condition of seasonal ataxia.

PMID- 22468005
TI  - Medicinal uses of mushrooms in Nigeria: towards full and sustainable
      exploitation.
AB  - For centuries, mushrooms have been appreciated as sources of food nutrients and
      pharmacologically important compounds useful in medicine. Yet not all the
      medicinal properties of mushrooms have been exploited. The above statement is
      more pertinent to mushrooms that are indigenous to Nigeria. There are inadequate
      data on the identity and medicinal properties of these wild mushrooms.
      Information on the ethnomedicinal uses of some mushrooms such as Pleurotus tuber
      regium used for headache, stomach pain fever, cold, constipation; Lentinus
      squarullosus for mumps, heart diseases; Termitomyces microcarpus for gonorrhea;
      Calvatia cyathiformis for leucorrhea, barreness; Ganoderma lucidum for treating
      arthritis, neoplasia; G. resinaceum used for hyperglycemia, liver diseases
      (hepatoprotector); G. applanatum used as antioxidant and for diabetes had been
      gathered through survey. The above information is mostly obtained from
      traditional herbalists who in most cases will not disclose their preparation
      compositions. A lot of these mushrooms are obtained only in the wild. Scientific
      documents of the identities and medicinal properties are still scanty.
      Preliminary studies on some species of Temitomyces, Lenzites and Lentinus species
      showed that they possess appreciable antimicrobial and antioxidant properties.
      Moreover, molecular characterization also reveals that they are not 100%
      homologous with existing sequences under the same name in GenBank. It is
      therefore pertinent that well structured studies on their ecology, identification
      and medicinal uses be carried out. This will make the full exploitation of the
      medicinal potentials of mushrooms indigenous to Nigeria realizable.

PMID- 22468006
TI  - Hypoglycaemic and hypotensive effects of Ficus exasperata vahl. (Moraceae) leaf
      aqueous extract in rats.
AB  - The hypotensive and hypoglycaemic effects of Ficus exasperata (Vahl) (family:
      Moraceae) leaf aqueous extract (FEE) were investigated in experimental rat
      models. In this study, spontaneously-hypertensive rats (SHR) (type 1 diabetes),
      obese Zucker (type 2 diabetes) and Wistar rats were used. Three (A, B and C)
      groups of rats, each group consisting of 10 rats, were used. Group A Wistar rats
      received distilled water in quantities equivalent to the volume of streptozotocin
      (STZ) and FEE administered intraperitoneally to treated rats. Diabetes mellitus
      was induced in the SHR group B rats by multiple low-dose (MLD) intraperitoneal
      injections of STZ (40 mg/kg body weight) to induce type 1 diabetes. The animals
      in group C were the obese Zucker rats with non-insulin-independent diabetes
      mellitus (NDDM) (type 2 diabetes) on genetic basis. F. exasperata leaf aqueous
      extract (FEE, 100 mg/kg/day p.o.) was administered orally by orogastric
      intubation to fasted Groups B and C rats. In groups B and C rats, administration
      of FEE commenced 4 weeks post STZ injection, and continued for the next 4
      consecutive weeks. Group A rats gave normal biochemical and morphological
      findings. Group B rats exhibited pronounced polyuria, hypoinsulinaemia,
      hyperlipidaemia and hyperglycaemia. These findings were also observed in group C
      rats, except that there was hyperinsilinaemia. Histopathological study of the
      aortic blood vessels showed extensive collagen fiber formation as well as
      perivascular fibrosis in both groups B and C rats. Four weeks of oral
      administration of F. exasperata leaf aqueous extract to diabetic groups of rats
      decreased blood glucose, blood pressure and lipid profiles. Administration of FEE
      (100 mg/kg p.o.) also restored the microanatomy of the blood vessels to almost
      normal levels. The findings of this study suggest that F. exasperata leaf aqueous
      extract possesses hypoglycaemic, hypotensive and hypolipidaemic properties. These
      findings lend biomedical and pharmacological support to the folkloric,
      ethnomedical uses of the plant in the management and/or control of diabetes and
      hypertension among the Yoruba-speaking people of Western Nigeria.

PMID- 22468007
TI  - Traditional medicine: past, present and future research and development prospects
      and integration in the National Health System of Cameroon.
AB  - Traditional medicine refers to health practices, approaches, knowledge and
      beliefs incorporating plant, animal and mineral based medicines, spiritual
      therapies, manual techniques and exercises, applied singularly or in combination
      to treat, diagnose and prevent illnesses or maintain well-being. In the last
      decade traditional medicine has become very popular in Cameroon, partly due to
      the long unsustainable economic situation in the country. The high cost of drugs
      and increase in drug resistance to common diseases like malaria, bacteria
      infections and other sexually transmitted diseases has caused the therapeutic
      approach to alternative traditional medicine as an option for concerted search
      for new chemical entities (NCE). The World Health Organisation (WHO) in
      collaboration with the Cameroon Government has put in place a strategic platform
      for the practice and development of TM in Cameroon. This platform aims at
      harmonizing the traditional medicine practice in the country, create a synergy
      between TM and modern medicine and to institutionalize a more harmonized
      integrated TM practices by the year 2012 in Cameroon. An overview of the practice
      of TM past, present and future perspectives that underpins the role in
      sustainable poverty alleviation has been discussed. This study gives an insight
      into the strategic plan and road map set up by the Government of Cameroon for the
      organisational framework and research platform for the practice and development
      of TM, and the global partnership involving the management of TM in the country.

PMID- 22468008
TI  - Anticholinesterase activity of endemic plant extracts from Soqotra.
AB  - A total of 30 chloroform and methanol extracts from the following endemic
      Soqotran plants Acridocarpus socotranus Olive, Boswellia socotranao Balf.fil,
      Boswellia elongata Balf. fil., Caralluma socotrana N. Br, Cephalocroton
      socotranus Balf.f, Croton socotranus Balf. fil.., Dendrosicycos socotrana
      Balf.f., Dorstenia gigas Schweinf. ex Balf. fil., Eureiandra balfourii Cogn. &
      Balf. fil., Kalanchoe farinaceae Balf.f, Limonium sokotranum (Vierh) Radcl. Sm),
      Oldenlandia pulvinata, Pulicaria diversifolia (Balf. and Pulicaria stephanocarpa
      Balf. were screened for their acetylcholinesterase inhibitory activity by using
      in vitro Ellman method at 50 and 200 ug/ml concentrations. Chloroform extracts of
      Croton socotranus, Boswellia socotrana, Dorstenia gigas, and Pulicaria
      stephanocarpa as well as methanol extracts of Eureiandra balfourii exhibited
      inhibitory activities higher than 50 % at concentration of 200 ug. At a
      concentrations of 50 ug, the chloroform extract of Croton socotranus exhibited an
      inhibition of 40.6 %.

PMID- 22468009
TI  - Gastro-protective effect of Crossopteryx febrifuga in Wistar rats.
AB  - Preparations of Crossopteryx febrifuga (Afzel.) Benth. (Rubiaceae) are widely
      used in Northern Nigeria in the therapeutic management of trypanosomiasis,
      malaria and painful inflammatory disorders. Previous studies have shown that the
      methanolic stem bark extract of Crossopteryx febrifuga possesses significant
      analgesic and anti-inflammatory properties possibly mediated via Non-selective
      inhibition of cyclo-oxygenase pathways. In the present study, the methanolic stem
      bark extract of Crossopteryx febrifuga was evaluated against ethanol- and
      piroxicam-induced ulceration in rats. Histopathological studies of the rat
      stomach tissues were also carried out in order to determine its safety profile on
      the gastrointestinal tract (git). The extract (25, 50 and100 mg extract/kg body
      weight) significantly (P<0.05) and dose-dependently reduced ulcer index induced
      by ethanol (24 - 92%) and piroxicam (81.81- 98.60%). Histopathology of the rat
      stomach tissues from control and extract-treated groups at 25 mg/kg body weight
      extract showed mild inflammation characterized by infiltration of inflammatory
      cells, while the extract treated groups at 50 and 100mg/kg body weight and 200 mg
      misoprostol/kg body weight group showed no obvious lesions. These results showed
      that the extract had no deleterious effects and was cytoprotective on the
      gastrointestinal tract (git). It can thus be developed as a safe alternative to
      conventional non-steroidal anti-inflammatory drugs (NSAIDs) for the management of
      painful inflammatory disorders.

PMID- 22468010
TI  - Effects of oral administration of Phyllanthus amarus leaf extract on the kidneys
      of adult wistar rats: a histological study.
AB  - Histological studies of the effects of oral administration of aqueous extract of
      Phyllanthus amarus commonly used in ethno medical practice in Africa for the
      management of various ailments such as kidney stones, dysentery, jaundice,
      diarrhoea and urogenital diseases on the kidney of adult Wistar rats were
      carefully studied. Rats of both sexes (n=24), average weight of 260g were
      randomly assigned into three groups: A, B and C of (n=8) in each group. Group A
      and B served as treatment groups (n=16) while group C (n=8) served as the
      control. The rats in the treatment groups (A & B) received 500mg/kg and 1000mg/kg
      body weight respectively of aqueous extract of Phyllanthus amarus orally through
      orogastric tube for twenty-eight days, while the control rats received equal
      volume of distilled water without the extract of Phyllanthus amarus added for the
      same period. The rats were fed with growers' mash purchased from Edo feeds and
      Flour Mill Ltd, Ewu, Edo state and were given water liberally. The rats were
      sacrificed on day twenty-nine of the experiment. The kidneys were carefully
      dissected out and quickly fixed in 10% formal saline for routine histological
      study after H&E method. The histological findings indicated that the treated
      sections of the kidneys showed hypertrophy of blood vessels, mild-severe
      infiltrate of chronic inflammatory cells and varying degrees of tubular necrosis
      when compared to the control sections. The findings indicated that the
      administration of Phyllanthus amarus extract has some adverse effects on the
      kidneys of adult Wistar rats. It is recommended that further studies aimed at
      corroborating these observations be carried out.

PMID- 22468011
TI  - Protective effect of Ssanghwa-tang fermented by Lactobacillus fermentum against
      carbon tetrachloride-induced acute hepatotoxicity in rats.
AB  - Ssanghwa-tang (SHT) is a traditional herbal medicine formula that has been used
      for the development of physical strength, relief of pain, and the reduction of
      fatigue. In this study, we fermented SHT with Lactobacillus fermentum (L.
      fermentum), Lactobacillus gasseri (L.gasseri), or Lactobacillus casei (L.casei)
      to investigate the hepatoprotective effects of SHT and fermented SHT with
      Lactobacillus on carbon tetrachloride (CCl(4))-induced liver injury in rats. Rats
      were given CCl(4) (1 ml/kg, 50% CCl(4) in olive oil) intraperitoneally and either
      SHT or fermented SHTs (15 ml/kg) was administered 30 min before CCl(4). At 24 hr
      after CCl(4) injection, the levels of transaminases in the serum were markedly
      increased. These increases were significantly attenuated by either SHT + L.
      fermentum or SHT+ L.gasseri. However, SHT and SHT + L.casei showed slight
      suppression of the increase of transaminases. The liver histological changes were
      diminished by treatment with SHT + L. fermentum. Additionally, the potential
      hepatoprotective effect of fermented-SHTs correlated with the amount of unknown
      metabolite which is produced during fermentation process with L. fermentum,
      L.gasseri, or L.casei. Therefore, these results suggest that the hepatoprotective
      effect of SHT may be improved by fermentation with L. fermentum and the
      intestinal bacterial enzyme activities may likely play an important role in the
      pharmacological action of herbal medicines.

PMID- 22468012
TI  - Detection and extraction of anti-Listerial compounds from Calligonum comosum, a
      medicinal plant from arid regions of Tunisia.
AB  - Calligonum comosum, a Tunisian plant from arid regions, is traditionally used in
      folk medicine to treat rural population microbial infections. The plant was
      investigated in vitro for its ability to inhibit the growth of Listeria ivanovii.
      Various aqueous and organic extracts were prepared from different plant tissues.
      Results indicated that ethanolic, methanolic and acetonic extracts from whole
      plant tissues except seeds, exhibited significant antibacterial activity with
      growth inhibition zones (9 - 18mm) as shown by the agar-well diffusion method.
      Minimum Inhibitory Concentration (MIC) of 0.65mg/ml was obtained in acetonic
      extract generated from C. comosum roots. Preliminary phytochemical analysis based
      on heat and protease treatments showed that bioactive extracts were stable up to
      10m in heating at 100 degrees C and that they resist protease digestion. Based on
      these latter results, the activity of organic extracts may be related to the
      presence of sterols, terpenoids, and/or phenolics. Overall, these results
      indicate that C. comosum organic extracts are probably useful in the control of
      food contamination by listerial species.

PMID- 22468013
TI  - Antifungal activity and acute toxicity of stem bark extracts of Drypetes
      gossweileri S. Moore-euphorbiaceae from Cameroon.
AB  - Drypetes gossweilleri S. Moore is a plant used in traditional medicine in
      Cameroon. The antifungal properties of its stem-bark crude extract and fractions
      DG(1), DG(2), DG(3), DG(4), DG(5), DG(6), DG(7), DG(8) and DG(9) were assayed by
      agar and broth dilution methods on solid and liquid media against C. Krusei, C.
      albicans, C. glabrata, T. mentagerophytes, M. langeroinii, M. gypeum, M.
      audouini, T. rubrum, T. soudanense, T. terrestre, A. flavus and A. niger. The
      results revealed a substantial antifungal effect with minimal inhibitory
      concentrations ranging respectively from 24.11ug/ml to 1562ug/ml for yeasts and
      from 3125ug/ml to 12500ug/ml for filamentous fungi. Among the fractions, fraction
      DG4 exerted the highest antifungal activity. Moreover, no toxic effect was
      noticed in male and female albinos Wistar rats treated per os with the crude stem
      bark's extract of Drypetes gossweileri at a dose up to 12g/kg of body weight. The
      phytochemical screening of the crude extract and fractions showed the presence of
      alkaloids, phenols, flavonoids, saponins, anthocyanines, anthraquinones, sterols,
      lipids and essential oils. Therefore, Drypetes gossweileri may be safe as
      phytomedecine for the treatment of fungal infections.

PMID- 22468014
TI  - What Works in Group Care? - A Structured Review of Treatment Models for Group
      Homes and Residential Care.
AB  - This paper presents findings from a structured review of treatment models that
      are relevant to group care and residential treatment settings for children
      involved with the child welfare system. Initiated and guided by The California
      Evidence-Based Clearinghouse for Child Welfare, five treatment models - Positive
      Peer Culture, Teaching Family Model, Sanctuary Model, Stop-Gap Model, and Re-ED -
      were reviewed for effectiveness. In this paper, each model s treatment features
      are described and relevant outcome studies reviewed in terms of their
      effectiveness as well as relevance for child welfare practice. Findings indicate
      that four of the models are either supported or promising in terms of evidence
      for effectiveness. Implications for group care practice and research are
      discussed.

PMID- 22468015
TI  - An interlaboratory comparison of bone lead measurements via K-shell X-ray
      fluorescence spectrometry: validation against inductively coupled plasma mass
      spectrometry.
AB  - (109)Cd-based K-shell X-ray fluorescence spectrometry (hereafter, for brevity,
      XRF) is used, often in epidemiological studies, to perform non-invasive, in vivo
      measurements of lead in bone. We conducted the first interlaboratory study of XRF
      via the circulation of nine goat tibiae in which the mean lead value ranged from
      4.0 ug g(-1) to 55.3 ug g(-1) bone mineral. The test tibiae were subsequently
      analyzed via nitric acid digestion followed by lead determination by inductively
      coupled plasma mass spectrometry (ICP-MS) - along with certified reference
      materials for bone lead - thus providing measurement traceability to SI units.
      Analysis of dried bone for lead via nitric acid digestion and ICP-MS yields mass
      fraction data in units of ug g(-1) dry weight. The mean bone lead value based on
      ICP-MS analysis ranged from 1.8 ug g(-1) to 35.8 ug g(-1) dry weight. For
      comparison purposes, XRF-measured Pb values (ug g(-1) bone mineral) were
      converted into the ICP-MS-measured units (ug g(-1)dry weight bone) by multiplying
      the former by the average ash fraction from the nine tibiae. Eight of the XRF
      systems did not yield a significant bias for any of the nine tibiae; one system
      was biased for one of the tibiae; two systems were biased for two tibiae; one
      system was biased for four tibiae; two systems (813-1 and 804-2) were biased for
      five tibiae and one system (801-1) was biased for six of the nine tibiae. Average
      bias for the systems (under those particular operating conditions) that were
      biased for the majority of samples ranged from -2.6 ug g(-1) (-15.7%) to 5.1 ug
      g(-1) (30.7%) dry weight bone. All participants now have the ICP-MS data,
      allowing any corrective actions deemed necessary to be implemented. The ICP-MS
      data, however, indicated that the lead mass fraction varied considerably with the
      sampling location within the tibiae, to the extent of exceeding XRF variability
      for the higher lead values. Material heterogeneity is an unavoidable reality of
      measuring lead in bone.

PMID- 22468016
TI  - Sibship size and educational attainment. A joint test of the Confluence Model and
      the Resource Dilution Hypothesis.
AB  - Studies on family background often explain the negative effect of sibship size on
      educational attainment by one of two theories: the Confluence Model (CM) or the
      Resource Dilution Hypothesis (RDH). However, as both theories - for substantively
      different reasons - predict that sibship size should have a negative effect on
      educational attainment most studies cannot distinguish empirically between the CM
      and the RDH. In this paper, I use the different theoretical predictions in the CM
      and RDH on the role of cognitive ability as a partial or complete mediator of the
      effect of sibship size to distinguish the two theories and to identify a unique
      RDH effect on educational attainment. Using sibling data from the Wisconsin
      Longitudinal Study (WLS) and a random effect Instrumental Variable model I find
      that, in addition to a negative effect on cognitive ability, sibship size also
      has a strong negative effect on educational attainment which is uniquely
      explained by the RDH.

PMID- 22468017
TI  - Proportional hazards model for competing risks data with missing cause of
      failure.
AB  - We consider the semiparametric proportional hazards model for the cause-specific
      hazard function in analysis of competing risks data with missing cause of
      failure. The inverse probability weighted equation and augmented inverse
      probability weighted equation are proposed for estimating the regression
      parameters in the model, and their theoretical properties are established for
      inference. Simulation studies demonstrate that the augmented inverse probability
      weighted estimator is doubly robust and the proposed method is appropriate for
      practical use. The simulations also compare the proposed estimators with the
      multiple imputation estimator of Lu and Tsiatis (2001). The application of the
      proposed method is illustrated using data from a bone marrow transplant study.

PMID- 22468018
TI  - Sortase-Mediated Transpeptidation for Site-Specific Modification of Peptides,
      Glycopeptides, and Proteins.
AB  - Sortases are a family of transpeptidases found in Gram-positive bacteria
      responsible for covalent anchoring of cell surface proteins to bacterial cell
      walls. It has been discovered that sortase A (SrtA) of Staphylococcus aureus
      origin is rather promiscuous and can accept various molecules as substrates. As a
      result, SrtA has been widely used to ligate peptides and proteins with a variety
      of nucleophiles, and the ligation products are useful for research in chemical
      biology, proteomics, biomedicine, etc. This review summarizes the recent
      applications of SrtA with special emphasis on SrtA-catalyzed ligation of
      carbohydrates with peptides and proteins.

PMID- 22468020
TI  - Associations between sperm abnormalities, breed, age, and scrotal circumference
      in beef bulls.
AB  - The objectives of this study were to determine the associations of breed, age,
      and scrotal circumference (SC), and their interaction, on the prevalence of sperm
      abnormalities in beef bulls in Alberta, Canada, and the percentage of
      satisfactory potential breeders identified during breeding soundness examination
      solely due to normal sperm morphology. Eosin-nigrosin stained semen smears and
      evaluation reports of 1642 bull breeding soundness evaluations were procured from
      6 veterinary clinics in Alberta. Sperm morphology was determined for at least 100
      sperm per bull. The most common defects were detached head [4.86% +/- 5.71%; mean
      +/- standard deviation (s)], distal midpiece reflex (6.19% +/- 9.13%), and bent
      tail (1.01% +/- 1.54%). Although breed, age, and SC did not significantly affect
      the prevalence of head or midpiece defects, morphologically normal or abnormal
      sperm, tail defects were more prevalent in Angus and Hereford bulls compared with
      other breeds. Overall, solely on the basis of sperm morphology, 1363 (83.0%)
      bulls were classified as satisfactory potential breeders and the remainder 279
      (17.0%) as unsatisfactory (> 30% abnormal sperm, > 20% defective heads, or both).
      Although not significantly different, the breed with the highest percentage of
      satisfactory potential breeders was Limousin (90.6%) and the lowest was Hereford
      (78.8%). That 17% of bulls subjected to breeding soundness evaluation were
      designated as unsatisfactory solely on the basis of sperm morphology highlights
      its importance.

PMID- 22468021
TI  - Association between physical properties of cervical mucus and ovulation rate in
      superovulated cows.
AB  - Possible associations between certain physical properties of cervical mucus (CM)
      and ovulation rate were studied in 21 superovulated Holstein cows. In CM samples
      collected at the beginning of estrus (0 h) and in 4 h intervals for the following
      24 h, the pH, the spinnbarkeit (spinability), and the crystallization value were
      measured. Blood samples, collected at the same time points with CM samples, were
      assessed for progesterone and estradiol concentrations. At 48 h the number of
      ovulated follicles was counted by transrectal ultrasonography and the animals
      were allotted into 2 groups according to the occurrence of at least one (group A,
      n = 16) or no (group B, n = 5) ovulations. The pH was lower (P < 0.05) at 8 h
      (7.00 + 0.24) in group A compared with group B (7.55 + 0.12). In group A,
      spinnbarkeit was significantly lower at 0 h and 20 h, and higher at 8 h and 16 h
      compared with group B (0 h: 2.50 + 0.82 versus 6.95 + 0.41; 20 h: 3.00 + 1.89
      versus 5.38 + 0.94; 8 h: 7.00 + 0.87 versus 2.75 + 0.43; 16 h: 7.00 + 1.41 versus
      4.30 + 0.71, for groups A versus B, respectively). Crystallization was
      significantly lower at 4 h (2.00 + 0.63) and 20 h (1.50 + 0.82) in group A
      compared with group B (3.13 + 0.32 at 4 h and 3.00 + 0.41 at 20 h). Progesterone
      at all time points, and estradiol at 16 h, 20 h, and 24 h were lower (P < 0.05)
      in group A than in group B. The pH, crystallization, estradiol, and progesterone
      differed (P < 0.05) within one group, while sbk differed within both groups.Our
      results imply that during the periovulatory period, steadily low progesterone
      concentrations trigger alterations of certain CM characteristics, while extremely
      high estradiol concentration could prevent the occurrence of these alterations.

PMID- 22468019
TI  - Recent Development in Carbohydrate Based Anti-cancer Vaccines.
AB  - The development of carbohydrate based anti-cancer vaccines is of high current
      interests. Herein, the latest development in this exciting field is reviewed.
      After a general introduction about tumor associated carbohydrate antigens and
      immune responses, the review is focused on the various strategies that have been
      developed to enhance the immunogenecity of these antigens. The results from
      animal studies and clinical trials are presented.

PMID- 22468022
TI  - The development of a novel percutaneous lung biopsy procedure for use on feedlot
      steers.
AB  - The purpose of this study was to develop a percutaneous lung biopsy technique to
      be used on steers in a commercial feedlot setting. Thirty-four crossbred steer
      and heifer calves from a commercial feedlot in southern Alberta were used in this
      study. The calves originated from the auction market and all were chronically
      affected with bovine respiratory disease (BRD). A technique was developed to
      obtain a lung sample from the right cranioventral lung lobe, intercostal space
      (ICS) 2, using a manual or an automatic biopsy instrument with a 14- or 12-gauge
      (ga) biopsy needle. Overall, lung parenchyma was successfully harvested in 55.9%
      of experimental animals and in 55.0% of lung biopsy trials. Compared with
      postmortem diagnosis, the biopsy resulted in the same pathologic diagnosis for
      75% of biopsy samples when evaluated using standardized criteria by the same
      veterinary pathologist. The success rate was 61.5% and 42.9% in a hospital or
      field setting, respectively. With an automatic instrument, lung was recovered
      from 57.9% and 37.5% of samples obtained using a 12- or 14-ga biopsy needle,
      respectively. One experimental animal or 2.9% of the total had fatal
      complications from the procedure. In a commercial feedlot setting, the procedure
      took 20 min for each animal. Percutaneous lung biopsy of the right cranioventral
      lung lobe may be a viable technique when used on feedlot steers affected with
      chronic pneumonia. These findings suggest that using an automatic instrument with
      either a 14- or 12-ga biopsy needle may yield lung samples that are suitable for
      histopathological evaluation. However, this technique needs to be further
      evaluated in a field setting.

PMID- 22468023
TI  - Comparative analysis of cholinesterase activities in food animals using modified
      Ellman and Michel assays.
AB  - This study investigated correlations between modified Ellman and Michel assay
      methods for measuring cholinesterase (ChE) activities. It also established a
      foundation for the applicability of measuring ChE activities in food animal
      species as biochemical biomarkers for evaluating exposure to and effects of
      organophosphorus and carbamate pesticides. Measuring ChE activities in blood and
      tissue is currently the most important method of confirming the diagnosis of such
      exposure. The study also characterized the level of ChE activity in the selected
      organs/tissues of these animals and determined the best organ/tissue in which to
      measure ChE activity. The ChE activities were found to be higher in cattle than
      in sheep and higher in erythrocytes than in plasma and serum. The anticoagulant
      heparin significantly affects AChE activity in plasma compared with
      ethylenediamine tetra-acetic acid (EDTA). Of the different tissues tested, the
      mean of ChE activities was found to be highest in tissue from liver, followed by
      lung, muscle, kidney, and heart for sheep and cattle. In pigs, the ChE activities
      tested higher in kidney, liver, lung, muscle, and heart. The highest activities
      of ChE were found in pigs, followed by cattle and sheep. There was no significant
      difference between the modified Ellman and Michel method, but the percentage
      coefficient of variance (%CV) values were higher when the Michel method was used.

PMID- 22468024
TI  - Increased levels of the 14-3-3 eta and gamma proteins in the synovial fluid of
      dogs with unilateral cranial cruciate ligament rupture.
AB  - The present study investigated whether the 14-3-3 eta and gamma proteins, which
      are potent matrix metalloprotease (MMP) stimulators, are detectable in the
      synovial fluid of dogs with cranial cruciate ligament rupture (CCLR). Synovial
      fluid samples from 7 dogs with unilateral CCLR and control samples from 4 dogs
      without a history of any joint inflammation or any other abnormalities underwent
      Western blot analysis for the 14-3-3 eta, gamma, and sigma proteins as well as
      MMP-1 and MMP-3. Craniocaudal and lateral radiographic projections of the stifle
      joint were evaluated for the presence and severity of 13 specific radiographic
      markers of osteoarthritis and graded numerically. The Spearman method was used to
      detect any correlation between the 14-3-3-eta level in the synovial fluid and the
      radiograph-based grade. The eta isoform was present only in the samples from the
      dogs with CCLR. The levels of 14-3-3-gamma, MMP-1, and MMP-3 were significantly
      higher in the samples from the dogs with CCLR than in the control samples (P <
      0.05). However, there was no significant difference between the CCLR and control
      samples in the level of the sigma isoform. The Spearman method showed a
      significant correlation between the 14-3-3-eta level in the synovial fluid and
      the presence of either patellar osteophytes or lateral or medial (or both)
      condylar periarticular osteophytes (P < 0.05). The MMP stimulatory effect of the
      14-3-3 eta and gamma isoforms may be the reason for the high levels of MMP-1 and
      MMP-3 observed. Thus, 14-3-3 proteins, especially the eta isoform, may be
      important markers of osteoarthritis caused by CCLR.

PMID- 22468025
TI  - Stability of vaccinia-vectored recombinant oral rabies vaccine under field
      conditions: a 3-year study.
AB  - Rabies is an incurable zoonotic disease caused by rabies virus, a member of the
      rhabdovirus family. It is transmitted through the bite of an infected animal.
      Control methods, including oral rabies vaccination (ORV) programs, have led to a
      reduction in the spread and prevalence of the disease in wildlife. This study
      evaluated the stability of RABORAL, a recombinant vaccinia virus vaccine that is
      used in oral rabies vaccination programs. The vaccine was studied in various
      field microenvironments in order to describe its viability and facilitate
      effective baiting strategies. Field microenvironments influenced the stability of
      this vaccine in this study. This study emphasizes the importance of understanding
      how vaccines perform under varying field conditions in order to plan effective
      baiting strategies.

PMID- 22468026
TI  - Assessment of Bdellovibrio bacteriovorus 109J killing of Moraxella bovis in an in
      vitro model of infectious bovine keratoconjunctivitis.
AB  - The objective of this study was to determine the potential of Bdellovibrio
      bacteriovorus 109J as an alternative non-chemotherapeutic treatment of infectious
      bovine keratoconjunctivitis (IBK). To accomplish this, various parameters of B.
      bacteriovorus predation of Moraxella bovis were determined in vitro. Initial
      passage of B. bacteriovorus using M. bovis as prey required 10 d for active
      cultures to develop compared with 2 d for culture on normal Escherichia coli
      prey; however by the 5th passage, time to active predatory morphology was reduced
      to 2 d. This high passage B. bacteriovorus culture [1 * 10(10) plaque forming
      units (PFU)/mL] killed 76% of M. bovis [1 * 10(7) colony forming units (CFU)/mL]
      present in suspension broth in a 4 h assay. The minimal level of M. bovis
      supporting B. bacteriovorus predation was 1 * 10(4) CFU/mL. To assess the ability
      of B. bacteriovorus to kill M. bovis on an epithelial surface mimicking IBK, an
      in vitro assay with Madin-Darby bovine kidney (MDBK) cells inoculated with 4 *
      10(7) CFU/mL M. bovis was used. Treatment with a B. bacteriovorus suspension (1.6
      * 10(11) PFU/mL) decreased adherence of M. bovis to MDBK cells by 6-fold at 12 h
      of treatment, as well as decreased the number of unattached M. bovis cells by 1.4
      fold. This study demonstrates that B. bacteriovorus has potential as an effective
      biological control of M. bovis at levels likely present in IBK-infected corneal
      epithelia and ocular secretions.

PMID- 22468027
TI  - Effect of in-water iodine supplementation on weight gain, diarrhea and oral and
      dental health of nursery pigs.
AB  - A farm trial was conducted to evaluate the effect of in-water iodine on piglet
      growth, the incidence of diarrhea, and the development of deleterious oral and
      dental conditions. A total of 208 weaned piglets were included in the study.
      Piglets were weighed 3 times: within 24 h of weaning, and 3 wk and 6 wk after
      weaning. A concentration of 1 ppm iodine was provided in their drinking water.
      Swabs were taken from all water nipples and water lines and pooled fecal samples
      were collected from all pen floors. Fecal samples were also collected from sows
      at weaning. The swabs and fecal samples were tested for the presence of
      Salmonella and Escherichia coli. Within 24 h of each weighing, a complete oral
      examination was performed on each piglet. No significant difference in growth (P
      > 0.05) or dental conditions (P > 0.05) was found among treatment groups during
      the period that iodine was added to the drinking water. After weaning, all
      deleterious oral conditions increased (oral lesions from weaning to 6 wk,
      staining and caries from weaning to 3 wk, gingivitis from 3 wk to 6 wk; P <
      0.05). Only gingivitis was found to be negatively associated with piglet weight
      (P < 0.05). Salmonella was cultured only twice from fecal samples and never from
      water nipples. Only 1 sow tested positive for Salmonella and E. coli O139: K82
      and O157:K"V17 were cultured only rarely from the water nipples. No signs of
      diarrhea were noted throughout the study. Adding an aqueous iodine supplement to
      nursery pigs, therefore, did not provide an advantage for either growth or oral
      condition. Deleterious oral conditions do increase after weaning, with gingivitis
      being associated with lower piglet weight.

PMID- 22468028
TI  - Presence and characterization of Campylobacter jejuni in organically raised
      chickens in Quebec.
AB  - The objective of this study was to estimate the presence of the important
      foodborne pathogen Campylobacter jejuni in organically raised chickens in the
      province of Quebec. The recovered isolates were further characterized for their
      antimicrobial resistance profile, autoagglutination property and chemotaxis.
      Antimicrobial resistance was evaluated using agar dilution for: tetracycline,
      erythromycin, chloramphenicol, ciprofloxacin, gentamicin, nalidixic acid,
      clindamycin, ampicillin, azithromycin, bacitracin, and ceftiofur.
      Autoagglutination was measured by monitoring optical density changes in a
      bacterial suspension after 3 h of incubation at room temperature. Chemotaxis was
      evaluated after a contact time of 3 h between isolates and mucin, using a
      quantitative protocol. A total of 10 lots of chickens was sampled in August and
      September 2009; half of them were positive for the presence of C. jejuni.
      Antimicrobial resistance was found only for tetracycline (44%), erythromycin
      (6%), azithromycin (6%) and clindamycin (2%). Variation was observed in the
      minimum inhibitory concentrations (MICs) for ceftiofur and bacitracin, for which
      C. jejuni possess intrinsic resistance. Autoagglutination and chemotaxis varied
      among isolates and lot-level differences in these were observed.
      Autoagglutination and chemotaxis levels appeared as independent isolate
      properties. Further monitoring and characterization of isolates originating from
      organic chickens is of interest since this type of production might represent
      another source of exposure of consumers to a variety of the foodborne pathogen C.
      jejuni.

PMID- 22468029
TI  - Comparison of bacterial culture, polymerase chain reaction, and a mix-enzyme
      linked immunosorbent assay for the detection of Salmonella status in grow-to
      finish pigs in western Canada with a Bayesian approach.
AB  - Among grow-to-finish pigs from 10 herds in Alberta and Saskatchewan, 23 (16%) of
      144 fecal samples were culture-positive and 40 (28%) of 144 pigs were
      seropositive for Salmonella. With a Bayesian model specifying dependence between
      the 2 tests, the sensitivity (Se) of culture and real-time polymerase chain
      reaction (RT-PCR) was 79% to 86%, depending on the cut-off value for the enzyme
      linked immunosorbent assay (ELISA). Culture specificity (Sp) was assumed to be
      100%; RT-PCR Sp was found to be 94%. The ELISA Se was 76% and 51% at optical
      density cut-off values >= 20% and >= 40%, respectively; the Sp was 94% at each
      cut-off value. The model showed some sensitivity to ELISA prior information, the
      ELISA Se being approximately 8% lower when informative prior information was
      specified in the model. When there was no adjustment for dependence between
      culture and RT-PCR, the posterior estimates for both culture and RT-PCR Se were
      11% higher than with the conditional-dependence model and had considerably
      narrower probability intervals, which suggests that correlation between culture
      and PCR is important and should be adjusted for in future studies.

PMID- 22468030
TI  - Serum insulin-like growth factor-1 measurements in dogs: performance
      characteristics of an automated assay and study of some sources of variation.
AB  - The aim of this study was to evaluate the performance characteristics of an
      automated immunoassay for canine insulin-like growth factor 1 (IGF-1) measurement
      and to investigate the possible effects of some sources of variation, such as
      diurnal variations, feeding/fasting cycles, and glucocorticoid administration, in
      dogs. The immunoassay evaluated had an adequate analytical performance with intra
      and inter-assay coefficients of variation (CVs) lower than 10%, linear
      regression equations with correlation coefficients of 0.9993 and 0.9988 after
      serial dilutions, and a limit of quantification of 7.1 ng/mL that was even lower
      than that reported by the manufacturer. The assay was significantly affected by
      hemolysis and lipemia producing a significant decrease in IGF-1 concentrations,
      but not by bilirubinemia.Serum IGF-1 concentrations did not show significant
      diurnal changes in fed or fasted dogs and were not affected by glucocorticoid
      administration.

PMID- 22468031
TI  - Formation of monoethylglycinexylidide (MEGX) in clinically healthy dogs.
AB  - Liver function tests help to investigate actual liver function. In dogs, only a
      few tests are available. We evaluated the formation of monoethylglycinexylidide
      (MEGX) in clinically healthy dogs to assess the usefulness of this liver function
      test in dogs. Twenty-five healthy dogs were used in this study. The MEGX test was
      done according to human protocols. The results of our study showed that dogs
      synthesize MEGX after the administration of lidocaine. There was no age
      dependence of this test in dogs and no significant difference between
      measurements obtained at 15 and 30 min after administration of lidocaine. Female
      dogs had significantly (P < 0.05) higher concentrations of MEGX 15 min after
      administration. The reference interval for dogs after 15 min is 34 to 79 MUg/L
      and after 30 min 39 to 89 MUg/L. In conclusion, the MEGX test may be an
      additional liver function test in dogs.

PMID- 22468032
TI  - EVENT SEGMENTATION.
AB  - One way to understand something is to break it up into parts. New research
      indicates that segmenting ongoing activity into meaningful events is a core
      component of ongoing perception, with consequences for memory and learning.
      Behavioral and neuroimaging data suggest that event segmentation is automatic and
      that people spontaneously segment activity into hierarchically organized parts
      and sub-parts. This segmentation depends on the bottom-up processing of sensory
      features such as movement, and on the top-down processing of conceptual features
      such as actors' goals. How people segment activity affects what they remember
      later; as a result, those who identify appropriate event boundaries during
      perception tend to remember more and learn more proficiently.

PMID- 22468033
TI  - Joint modelling of longitudinal outcome and interval-censored competing risk
      dropout in a schizophrenia clinical trial.
AB  - The 'Clinical antipsychotic trials in intervention effectiveness' study, was
      designed to evaluate whether there were significant differences between several
      antipsychotic medications in effectiveness, tolerability, cost and quality of
      life of subjects with schizophrenia. Overall, 74 % of patients discontinued the
      study medication for various reasons before the end of 18 months in phase I of
      the study. When such a large percentage of study participants fail to complete
      the study schedule, it is not clear whether the apparent profile in effectiveness
      reflects genuine changes over time or is influenced by selection bias, with
      participants with worse (or better) outcome values being more likely to drop out
      or to discontinue. To assess the effect of dropouts for different reasons on
      inferences, we construct a joint model for the longitudinal outcome and cause
      specific dropouts that allows for interval-censored dropout times. Incorporating
      the information regarding the cause of dropout improves inferences and provides
      better understanding of the association between cause-specific dropout and the
      outcome process. We use simulations to demonstrate the advantages of the joint
      modelling approach in terms of bias and efficiency.

PMID- 22468034
TI  - Molecular clinical biochemistry in laboratory medicine: the present and the
      future.

PMID- 22468035
TI  - Allergens/Antigens, toxins and polyketides of important Aspergillus species.
AB  - The medical, agricultural and biotechnological importance of the primitive
      eukaryotic microorganisms, the Fungi was recognized way back in 1920. Among
      various groups of fungi, the Aspergillus species are studied in great detail
      using advances in genomics and proteomics to unravel biological and molecular
      mechanisms in these fungi. Aspergillus fumigatus, Aspergillus flavus, Aspergillus
      niger, Aspergillus parasiticus, Aspergillus nidulans and Aspergillus terreus are
      some of the important species relevant to human, agricultural and
      biotechnological applications. The potential of Aspergillus species to produce
      highly diversified complex biomolecules such as multifunctional proteins
      (allergens, antigens, enzymes) and polyketides is fascinating and demands greater
      insight into the understanding of these fungal species for application to human
      health. Recently a regulator gene for secondary metabolites, LaeA has been
      identified. Gene mining based on LaeA has facilitated new metabolites with
      antimicrobial activity such as emericellamides and antitumor activity such as
      terrequinone A from A. nidulans. Immunoproteomic approach was reported for
      identification of few novel allergens for A. fumigatus. In this context, the
      review is focused on recent developments in allergens, antigens, structural and
      functional diversity of the polyketide synthases that produce polyketides of
      pharmaceutical and biological importance. Possible antifungal drug targets for
      development of effective antifungal drugs and new strategies for development of
      molecular diagnostics are considered.

PMID- 22468036
TI  - Serum cystatin C levels in renal transplant recipients.
AB  - Cystatin C is an emerging parameter for the assessment of renal allograft
      function. The objective of the study was to compare the efficacy of serum
      cystatin C (SCys) with the established parameter serum creatinine (SCr) in the
      assessment of renal function in renal transplant recipients (RTR). The glomerular
      filtration rate (GFR) of 30 renal transplant patients and 29 control subjects was
      determined using (99m)Tc Diethylene-triamine-penta-acetate (DTPA) method. SCr was
      measured using an automated Jaffe's assay and SCys was measured using latex
      particle enhanced turbidimetric immuno assay (PETIA). The modification of diet in
      renal disease (MDRD) formula was used to calculate GFR from SCr, while the Le
      Bricon formula was used to derive GFR based on SCys. Statistical analysis was
      performed using MedCalc software. SCr and SCys levels were significantly higher,
      while DTPA clearance was significantly lower in RTR (P < 0.0001) when compared
      with controls. The correlation coefficient (r value) between calculated GFR based
      on MDRD method and DTPA clearance was 0.343 (P = 0.06) while the calculated GFR
      based on Le Bricon formula was 0.694 (P < 0.001). The results have shown that
      SCys is a better parameter than SCr in assessing renal function in RTR. The
      inclusion of SCys as an additional parameter would certainly help in detection of
      even a marginal decline in renal function and also in adjusting the dosage of
      immunosuppressive drugs.

PMID- 22468038
TI  - Application of sigma metrics for the assessment of quality assurance in clinical
      biochemistry laboratory in India: a pilot study.
AB  - Ensuring quality of laboratory services is the need of the hour in the field of
      health care. Keeping in mind the revolution ushered by six sigma concept in
      corporate world, health care sector may reap the benefits of the same. Six sigma
      provides a general methodology to describe performance on sigma scale. We aimed
      to gauge our laboratory performance by sigma metrics. Internal quality control
      (QC) data was analyzed retrospectively over a period of 6 months from July 2009
      to December 2009. Laboratory mean, standard deviation and coefficient of
      variation were calculated for all the parameters. Sigma was calculated for both
      the levels of internal QC. Satisfactory sigma values (>6) were elicited for
      creatinine, triglycerides, SGOT, CPK-Total and Amylase. Blood urea performed
      poorly on the sigma scale with sigma <3. The findings of our exercise emphasize
      the need for detailed evaluation and adoption of ameliorative measures in order
      to effectuate six sigma standards for all the analytical processes.

PMID- 22468037
TI  - Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1,
      rs41423247) on Blood Pressure, Glucose in Northern Indians.
AB  - Glucocorticoids and its receptor are known to be involved in the dysregulation of
      hormone and lipid levels. Therefore, we evaluated the association of Bcl1 gene
      polymorphism of glucocorticoids receptor (GCR) gene variant with hormone and
      lipid levels in Northern Indians obese. A total of 435 obese and non-obese age
      matched subjects were included in the case-control study. Lipid and hormonal
      levels were estimated using standard protocols. Analysis of +646 C>G NR3C1 gene
      polymorphism was done using PCR-RFLP. The frequencies of GR Bcl1, C>G genotypes
      and alleles did not differ significantly (P > 0.05) between obese and non-obese.
      The +646 G allele carriers had higher waist to hip ratio, blood pressure, insulin
      and glucose levels than non-carriers in obese subjects while diastolic blood
      pressure and glucose in non-obese. The NR3C1, +646 C>G polymorphism did not
      associate with obesity. However, the GG genotype may modulate blood pressure,
      blood glucose and hormonal levels in northern Indians.

PMID- 22468039
TI  - Role of Plasma MMP 9 levels in the Pathogenesis of Chronic Pancreatitis.
AB  - Pancreatic fibrosis is a key pathological feature in the etiology of chronic
      pancreatitis that leads to obliteration of exocrine and endocrine pancreatic
      tissues and its replacement by fibrous tissue resulting in clinical
      manifestations. Matrix metalloproteinase 9 is a member of the MMP family that is
      also known as gelatinase B, degrades type IV collagen of extracellular matrix and
      basal membrane. The present study is aimed at evaluating the clinical
      significance of plasma concentration of MMP-9 in chronic pancreatitis. The
      samples were obtained from 112 chronic pancreatitis patients and an equal number
      of age and sex matched healthy controls. MMP-9 levels were quantitatively
      measured by ELISA assay. Statistical analysis was applied to test the
      significance of results. The present study revealed a significant increase of
      plasma MMP 9 levels in chronic pancreatitis patients compared to control
      subjects. Elevated levels were also observed in all the patient groups compared
      to control subjects with regard to sex, age, addictions etc. MMP-9 degrades the
      type IV collagens in normal basement membrane, which in turn activates the
      pancreatic stellate cells which promote the development of pancreatitic fibrosis.
      Thus, elevated plasma levels of MMP-9 may act as a susceptibility factor for the
      development of chronic pancreatitis.

PMID- 22468040
TI  - Involvement of Depressive Catecholamines as Thrombosis Risk/Inflammatory Markers
      in Non-Smoker, Non-Obese Congestive Heart Failure, Linked to Increased Epidermal
      Growth Factor-Receptor (EGF-R) Production.
AB  - The EGF-R, also known as HER-1 or erbB-1 (EGF-R/HER-1/erbB-1), is a member of the
      human epithelial receptor tyrosine kinase family. sEGF-R is considered to play a
      role in cardiac (patho)physiology. We aimed to investigate whether soluble EGF-R
      is increased in congestive heart failure (CHF) patients and if related to disease
      severity. Soluble EGF-R, vitamin D, parathyroid hormone (PTH) was studied, and
      being evaluated in relation to Ca(2+), lipids, hsCRP, fibrinogen, serotonin,
      norepinepherine (NE). The study compared non-smoker, non-obese male CHF patients
      (n = 50) with age and gender-matched essential hypertension (HTN) patients (n =
      20). Moreover, comparison with healthy control volunteers (n = 20) were employed.
      EGF-R/HER-1/erbB-1 was higher (P = 0.013) in 50 CHF male patients mean 12 +/- 0.7
      fmol/ml, than in 20 HTN, 9.25 +/- 0.6 fmol/ml or in 20 controls, 6.25 +/- 1
      fmol/ml. Serum EGF-R levels correlated positively with hsCRP and NE, and were
      highest among CVD patients (n = 70) as well as negatively with vitamin D and HDL
      C. EGF-R/HER-1/erbB-1 levels are increased in HTN and more in CHF patients. This
      study confirms a strong association between catecholamines as well as EGF-R/HER
      1/erbB-1 levels with PTH and low vitamin D levels, being related to
      hyperlipidemia and inflammation (hsCRP and fibrinogen) in CVD. Moreover,
      contributing to the complex process of the inflammatory component of
      atherosclerosis in hypertensive patients that leads eventually to CHF.

PMID- 22468041
TI  - Quantitative Assessment of Expression of Lactate Dehydrogenase and its Isoforms 3
      and 4 may Serve as Useful Indicators of Progression of Gallbladder Cancer: A
      Pilot Study.
AB  - We have studied the expression of lactate dehydrogenase and its isoforms in gall
      bladder cancer, cholelithiasis and chronic cholecystitis. Quantitative and
      qualitative assays of lactate dehydrogenase and its various isoforms were carried
      out in the blood sera of patients and healthy controls along with parallel
      estimation of various liver function test enzymes. Statistical analysis was done
      using the software Graph Pad Prism. Significantly high expression of lactate
      dehydrogenase along with alkaline phosphatase and total bilirubin (P <= 0.05) was
      observed in all the three clinical conditions as compared to controls. LDH showed
      an increasing trend from stage I to stage IV of GBC indicating a significant
      positive association with the disease progression. The levels of LDH 3 and 4
      isoforms appeared significantly more elevated in GBC than cholelithiasis or
      chronic cholecystitis. We suggest that a careful estimation of total LDH and its
      isoforms 3 and 4 alone or along with alkaline phosphatase and total bilirubin
      during different clinical stages, like chronic cholecystitis, cholelithiasis and
      GBC, may prove to be a potentially useful biomarker in the prognostic management
      of gall bladder diseases, specifically GBC.

PMID- 22468042
TI  - Effect of oxidized phosphatidylcholine on biomarkers of oxidative stress in rats.
AB  - In this study it was planned to investigate the effect of oxidized
      phosphatidylcholine (derived from egg) feeding on lipid peroxidation of different
      tissues in rats. Male Wistar albino rats were fed oxidized and unoxidized
      phosphatidylcholine for 2 and 4 weeks, respectively. During the period of study
      food intake and body weights of animals increased gradually. Animals fed oxidized
      phosphatidylcholine for 2 and 4 weeks showed 33 and 15% spontaneous hemolysis of
      red blood cells in vitro. Under identical experimental conditions animals given
      unoxidized phosphatidylcholine showed 14.5 and 13.4% hemolysis for 2 and 4 week's
      period, respectively. Thiobarbituric acid reactive substances (TBARS) level in
      thymus, spleen, kidney, heart, liver and lung significantly increased in rats
      given oxidized phosphatidylcholine as compared to unoxidized group. Furthermore,
      in oxidized phosphatidylcholine group TBARS values in kidney, liver and lungs
      continued to rise for 4 weeks of treatment while TBARS level in heart, spleen and
      thymus was found to be decreased at the end of 4 weeks of oxidized
      phosphatidylcholine feeding. Plasma triacylglycerol and cholesterol was found to
      increase in rats who had received oxidized phosphatidylcholine for 2 weeks. These
      findings suggest that excess and persistent intake of oxidized
      phosphatidylcholine can cause significant damage to organs.

PMID- 22468043
TI  - Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic
      Hepatitis B and C Viral Infections.
AB  - The present study evaluated the plausible role of circulating biomarkers in
      immune pathogenesis of chronic hepatitis considered a priority in clinical
      hepatology. Total viral load of chronic hepatitis B virus (HBV) and hepatitis C
      virus (HCV) patients was quantified and correlation studies were performed with
      circulating levels of Th1/Th2 cytokines; C reactive protein and circulating
      nucleosomes; glutathione reductase (GR) and superoxide dismutase. To our
      knowledge, the study is first among its kind that validates strong positive
      correlation of viral load with IL-4, IL-6, GR in HBV and IL-6, IL-10, GR in HCV
      infections. Although, multi-centric studies including large cohorts are required
      for translating our findings to clinical practice, however, role of these
      biomarkers with potential diagnostic or prognostic significance might be helpful
      in clinical assessment of high-risk individuals, thereby, designing
      interventional strategies, towards development of personalized medicare. The
      results of our study also offer valuable insights of immune signaling mediators
      engaged in development of hepatocellular carcinoma.

PMID- 22468044
TI  - Effect of Vitamin E on sP-Selectin Levels in Pre-Eclampsia.
AB  - P-selectin, a cell adhesion molecule is elevated in many inflammatory conditions
      including preeclampsia which is characterized by generalized endothelial
      dysfunction and vasoconstriction presumably due to free radicals or mediators
      released by defective placentation. Vitamin E has been documented to protect cell
      membranes from oxidative damage and also decrease platelet aggregation. The role
      of vitamin E in pre-eclampsia is contradictory and hence the study was
      undertaken. Soluble P-selectin was measured by ELISA and Vitamin-E levels in
      plasma was estimated spectrofluorometrically. In our study the effect of
      supplementation of 400 IU/day of Vitamin E (a-tocopheryl acetate) to patients of
      pre-eclampsia showed significant decreased levels of soluble P-selectin by 2nd
      week as compared to patients given placebo (P = 0.005). In this short period of
      study no direct correlations were observed between Vitamin E or P-selectin levels
      with blood pressure as well as with proteinuria. Future studies may focus on the
      effect of a-tocopheryl acetate or the phosphate form of Vitamin-E, recently
      proposed to be the more active form on other inflammatory markers like IL-6, an
      important stimuli of P-selectin release in pre-eclampsia.

PMID- 22468045
TI  - Adiponectin gene polymorphism and its association with type 2 diabetes mellitus.
AB  - Mutations in different regions of adiponectin gene have been reported to be
      associated with obesity, atherosclerosis and type 2 diabetes mellitus. The
      present study was aimed to investigate the association among SNP 45 T > G of
      adiponectin gene and type 2 diabetes in South Indian population. 75 clinically
      diagnosed case of type 2 diabetes were studied and compared with 75 apparently
      healthy controls. The genotype frequency of SNP45 T > G in exon 2 of adiponectin
      gene was determined by PCR based restriction enzyme analysis using the
      restriction enzyme SmaI. (recognition site: CCC?GGG). Three kind of genotypes:
      wild type TT (470 bp), heterozygous type TG (470 bp, 336 bp, 134 bp) and
      homozygote mutant type GG (336 bp, 134 bp) were studied. A positive association
      has been found between SNP45 T > G and type 2 diabetes in the study population (P
      = 0.010, OR = 3.797, 95% CI = 1.312-10.983). Therefore, SNP45T > G in adiponectin
      gene may be one of the risk factors for type 2 diabetes.

PMID- 22468046
TI  - Are we using Thyroid Function Tests Appropriately?
AB  - Thyroid function tests are very important for the diagnosis and monitoring of
      patients with thyroid dysfunction. The guidelines recommend serum thyroid
      stimulating hormone (TSH) as the single most reliable test to diagnose all common
      forms of hypothyroidism and hyperthyroidism. The aim of this study was to analyze
      the ordering pattern for thyroid function tests by physicians and the analysis of
      results based on the clinical history. The mean age of the patients was 32.5 +/-
      6.5 years. Majority of samples (87.7% of total) were received from the
      departments of Medicine and Gynae. Thyroid profiles (47.5%) were ordered more
      frequently as compared to TSH only (46%). There was no significant difference in
      the percentage of normal reports for both types of tests. 77.8% of TFT and 76.6%
      of TSH samples had results within the reference range. The percentage of abnormal
      results was 13.7% in the patients who were screened for thyroid disorders. There
      is a need to redefine the case definition for thyroid dysfunction and order the
      appropriate test in a rational and cost effective manner.

PMID- 22468047
TI  - Serum total PSA and free PSA in breast tumors.
AB  - Now a days measurement of molecular forms of PSA has gained importance in
      clinical practice. Several studies have demonstrated the production of PSA in
      female tissues, such as breast. The present piece of work has been undertaken
      with an objective to estimate the relative proportion of the molecular forms of
      PSA in serum along with serum testosterone in benign and malignant breast tumor
      cases and to analyze their association with the severity of the disease process
      34 malignant and 26 benign breast disease cases along with 33 healthy controls of
      same age group were enrolled in this study for evaluation. Serum testosterone was
      measured by ELISA, whereas serum total PSA (TPSA) and free PSA (FPSA) were
      estimated by electrochemiluminescence immunoassay. A significant rise of fasting
      plasma glucose along with prominent dyslipidemia was observed in breast tumor
      cases. Marked rise in serum testosterone as well as TPSA and FPSA was documented
      in both benign and malignant breast tumor cases. Serum testosterone revealed a
      significant positive association with both TPSA and FPSA pointing towards an
      etiological association between them. However, surgical removal of tumor mass
      resulted in a marked decline of presurgical value of both TPSA and FPSA with a
      non-significant fall in serum testosterone revealing tumor tissue as the source
      of FPSA and TPSA. Thus, estimation of PSA provides prognostic information that
      may assist in future treatment.

PMID- 22468048
TI  - Plasma fibronectin concentration in obese/overweight pregnant women: a possible
      risk factor for preeclampsia.
AB  - Plasma fibronectin (FN) levels in obese/overweight and non-obese pregnant women
      were evaluated as a possible risk factor for preeclampsia. A total of one hundred
      and sixty three pregnant women attending antenatal clinic at University of
      Calabar Teaching Hospital participated in the study and sixty non-pregnant women
      served as control. About 77 (47.24%) of the pregnant women were followed up for
      any subsequent development of preeclampsia during the pregnancy. Fibronectin
      levels in plasma were measured by ELISA assay and serum total protein, urea and
      creatinine were determined spectrophotometrically. The mean plasma FN
      concentration of non-obese pregnant women in first trimester was lower than those
      of the non-pregnant women by 24%, but however, increased to the non-pregnant
      level in second and third trimesters. Obese/overweight pregnant women had
      significantly (P < 0.05) higher values than non-obese pregnant women in second
      and third trimesters. FN in obese/overweight pregnant women correlated positively
      with mean arterial blood pressure (MAP: r = 0.414, P = 0.04). About 28.57% of the
      pregnant women with FN above cut off point of 330 MUg/ml at 18-24 weeks of
      gestation developed preeclampsia. This value increased to 40.0% when only the
      obese/overweight women were considered. On analysis of both fibronectin >330
      MUg/ml and MAP > 90, the predictive value increased to 66.7%. We therefore
      conclude that elevated FN may be regarded as a risk factor of preeclampsia
      especially among the obese women.

PMID- 22468049
TI  - Correlation of adiponectin and leptin with insulin resistance: a pilot study in
      healthy north Indian population.
AB  - The increasing incidence of obesity, leading to metabolic complications is now
      recognized as a major public-health problem. Insulin resistance is a central
      abnormality of the metabolic syndrome, or syndrome X, originally hypothesized by
      Reaven Insulin resistance is more strongly linked to intra abdominal fat than to
      fat in other depots. Adipose tissue secretes numerous factors (adipokines) known
      to markedly influence lipid and glucose/insulin metabolism, oxidative stress, and
      cardiovascular integrity. Some of these adipokines have been shown to directly or
      indirectly affect insulin sensitivity through modulation of insulin signaling and
      the molecules involved in glucose and lipid metabolism. A pilot study was
      conducted with 80 healthy subjects who were non diabetic, non hypertensive and
      having no family history of hypertension, the aim was to evaluate the correlation
      of adiponectin and leptin levels with obesity and insulin resistance markers in
      healthy north Indian adult population. Serum leptin, adiponectin and insulin was
      estimated by sandwich ELISA method. In our study, Leptin correlated significantly
      with BMI (P value of 0.0000), WC (P value = 0.007), and HC (P value = 0.000).
      leptin showed significant positive correlation with fasting insulin (P value
      0.002), post prandial insulin (P value = 0.000) and HOMA-IR (P value = 0.002).
      Adiponectin showed significant positive correlation with triglycerides (P value =
      0.038), strong negative correlation with HDL-cholesterol (P value = 0.017). Serum
      concentrations of leptin are associated with central body fat distribution.
      Insulin resistance and adiponectin is associated with dyslipidemia and these all
      disorders may ultimately lead to metabolic syndrome.

PMID- 22468050
TI  - Diagnosis, evaluation, and treatment of lead poisoning in general population.
AB  - Among the heavy metals, lead still remains the major toxic pollutant of the
      environment. Human exposure to lead can occur through numerous pathways including
      air, food, dust, soil, and water. In the present study 14 lead poisoned patients
      with non-occupational lead exposure were evaluated. They were followed up and
      compared against the controls with no history of lead exposure. The patients had
      high blood lead levels and symptoms of weakness, dizziness, abdominal pain,
      generalized body ache, loss of appetite, and anxiety. Repeated course of
      chelation therapy helped to bring down their body burden of lead. Alternative
      sources for lead exposure can cause severe lead poisoning in general population.
      Screening and medical management of such individuals is very important to
      identify and eliminate sources of lead. The treatment and management requires a
      thorough medical evaluation and environmental intervention.

PMID- 22468051
TI  - Role of cytokines in the pathogenesis of non-alcoholic Fatty liver disease.
AB  - A number of factors are linked with non-alcoholic fatty liver diseases (NAFLD), a
      condition that ranges from clinically benign fatty liver to its more severe form,
      non alcoholic steatohepatitis (NASH). In this study, we evaluated the role of
      cytokines secreted from adipose tissue in the pathogenesis and progression of
      NAFLD. We also compared anthropometric profile, lipid profile and insulin
      resistance data in 105 NAFLD patients with 77 normal subjects. These subjects
      showed a normal serum albumin level, prothrombin time and renal function but
      elevated aminotransferases. Predisposing factors were diabetes mellitus (35%),
      overweight (56%) and hyperlipidemia (44%). Insulin resistance (IR), determined by
      homeostasis model assessment (HOMA) was confirmed in 70% patients with NAFLD and
      42% patients fulfilled the minimum criteria for insulin resistance syndrome
      (IRS). NAFLD patients showed elevated levels of pro-inflammatory cytokines tumor
      necrosis factor (TNF)-alpha, and interleukin (IL)-6, while anti-inflammatory
      cytokines IL-4 level decreased and IL-10 level remain unchanged; however, TGF
      beta1 level elevated significantly compared to normal subjects. While insulin
      level and HOMA-IR both were significantly positively correlated with BMI, waist
      to-hip ratio, total cholesterol, VLDL-cholesterol, triglyceride and TGF-beta1;
      glucose, IL-6 and TNF-alpha levels were significantly positively correlated with
      HOMA-IR only. In conclusion, pro-inflammatory cytokines play an important link
      between metabolic and liver disorders in the fat accumulation, and thereby cause
      IR, inflammation and liver fibrosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The
      online version of this article (doi:10.1007/s12291-011-0121-7) contains
      supplementary material, which is available to authorized users.

PMID- 22468052
TI  - Comparison Between Serum hsCRP and LDL Cholesterol for Search of a Better
      Predictor for Ischemic Heart Disease.
AB  - Acute myocardial Infarction is one of the major causes of morbidity & mortality
      in world and atherosclerosis is the major cause of ischemic heart disease. In
      order to determine the better clinical marker of atherosclerosis, we estimated
      serum low-density lipoprotein (LDL-C) and high sensitivity C-reactive protein
      (hsCRP). Hundred patients of myocardial infarction and 100 controls irrespective
      of age and sex were studied for these parameters over a period of 2 years. The
      statistical analysis showed that the serum hsCRP was significantly raised in
      myocardial infarction cases than controls (P < 0.01) but LDL-C was not (P >
      0.05). We conclude that the serum hsCRP has better predictive value for risk of
      atherosclerosis.

PMID- 22468053
TI  - End stage renal disease, differential diagnosis, a rare genetic disorder: bardet
      biedl syndrome: case report and review.
AB  - End stage renal disease (ESRD) represents a clinical condition in which there is
      an irreversible loss of endogenous renal function. Both structural and functional
      abnormalities of the kidney are associated with increased morbidity, mortality.
      Bardet-Biedel syndrome (BBS) is one of the rare genetic disorders with prevalence
      of 1 in 1, 40,000-1 in 1,60,000 worldwide. ESRD in BBS patients is the final
      stage of the disease, increasing mortality in youth.

PMID- 22468054
TI  - Future of surgery and shrinking surgeon.

PMID- 22468056
TI  - External coloanal anastomosis without covering stoma in low-lying rectal cancer.
AB  - The aim of this study was to evaluate the safety and functional outcome of
      external coloanal anastomosis without covering stoma in treating low-lying rectal
      cancer. All patients undergoing the coloanal anastomosis for low lying rectal
      carcer in the Department of General Surgery, Minia University Hospital, between
      May 2006 and May 2009 were included. Seventy two patients underwent coloanal
      anastomosis, and follow up was available for all patients. Mean follow up period
      was 12.6 +/- 4.7 months. Postoperatively, fecal continence was normal in 84.7% of
      patients. Postoperative complications included anastomotic fistula in 3 patients
      (4.2%) and anastomotic stenosis in 6 patients (8.3%). There was no effect of pre
      or postoperative adjuvant therapy on the procedure outcome. There was no local
      recurrence during follow up period. Three patients died at the end of follow up
      period due to distant metastasis. In treatment of low-lying rectal cancer,
      abdominoperineal resection should be avoided if coloanal anastomosis provides
      similar control of the disease as it is safe and has good functional results and
      acceptable complication rate.

PMID- 22468057
TI  - Study of immunohistochemistry in prostatic lesions with special reference to
      proliferation and invasiveness.
AB  - Prostatic lesions on routine staining sometimes cause diagnostic dilemma
      especially in premalignant lesions like atypical adenomatous hyperplasia and
      prostatic intraepithelial neoplasia. Benign small acinar lesions also may be
      difficult to differentiate from small acinar adenocarcinoma. An important
      differentiating point is the loss of basal cell layer in adenocarcinoma and its
      presence in benign lesions. Basal cell markers (e.g. 34betaE12 cytokeratin) &
      proliferative markers (e.g. AgNOR and PCNA) can help in this regard. Total 60
      cases of different prostatic lesions studied. After history taking, clinical
      examination, radiological & other investigations were done. Routine H&E staining,
      immunohistochemical staining against 34betaE12 cytokeratin & proliferative
      markers (AgNOR & PCNA) was performed. Statistically significant differences found
      in expression of 34betaE12 cytokeratin and proliferative markers between benign,
      premalignant and malignant prostatic lesions. Basal cell markers and
      proliferative markers are important parameters to distinguish between different
      benign, premalignant and malignant prostatic lesions.

PMID- 22468055
TI  - Laparoscopic cholecystectomy in patients with cardiac dysfunction.
AB  - Laparoscopic cholecystectomy remains the standard treatment for cholelithiasis.
      Ever increasing number of patients with myriad of medical illness is being
      treated by this technique. However, significant concern prevails among the
      surgical community regarding its safety in patients with cardiac co-morbidity.
      Patients with significant cardiac dysfunction and multiple co-morbidities were
      prospectively evaluated. Patients were assessed by cardiologists and
      anesthesiologists and laparoscopic cholecystectomy was performed. Patient
      demographics, details of peri-operative management and post-operative
      complications were studied. Between March 2005 and January 2009, 28 patients (M:F
      = 21:7) with mean age of 60 years (range 26-78) and having significant cardiac
      dysfunction had undergone laparoscopic cholecystectomy. Of these, 24 patients
      were in NYHA class-II, while 4 belonged to class-III. Left ventricular ejection
      fraction, as recorded by transthoracic echocardiography, was 20-30% in 13 (46%)
      patients and 30-40% in the rest 15 (54%). In addition, 13 (46%) patients had
      regional wall motion abnormalities, 11 (39%) patients had cardiomyopathy, 2 (7%)
      patients had valvular heart disease while 12 (43%) patients had prior cardiac
      interventions. Following laparoscopic cholecystectomy, hypertension (3),
      tachyarrhythmia (4) and bradycardia (1) were the commonest events encountered.
      One patient required laparotomy to deal with peritonitis in the immediate
      postoperative period and succumbed to myocardial infarction, but all other
      patients made an uneventful recovery. With appropriate cardiological support,
      laparoscopic cholecystectomy may be safely performed in patients with significant
      cardiac dysfunction.

PMID- 22468058
TI  - Comparison of immunohistochemistry with conventional histopathology for
      evaluation of sentinel lymph node in breast cancer.
AB  - The best method of pathological evaluation of sentinel lymph node in breast
      cancer has not been agreed upon. Immunohistochemical (IHC) techniques have shown
      a greater sensitivity over conventional histology for the detection of
      micrometastais. The aim of the study was to determine whether IHC for Epithelial
      Membrane Antigen (EMA) on the sentinel node could be more sensitive than
      conventional histology for diagnosing micrometastasis in sentinel lymph nodes.
      Eighty-four clinically node negative breast cancer patients underwent sentinel
      node biopsy at time of surgery for breast cancer. The node was subjected to
      conventional histopathology as well as IHC for EMA. The sensitivity of histology
      viz a viz IHC for EMA for detection of sentinel node metastasis was 88% and the
      specitficity was 96%. The overall diagnostic accuray of histology viz a viz IHC
      was 93%. There were 4 patients with micrometastasis (<2.0 mm), which were
      positive on IHC but negative on histology. Two patients with poorly
      differentiated breast cancer had a false negative IHC for EMA result as compared
      to histology. Immunohistochemistry for Epithelial Membrane Antigen can increase
      the detection rate of micrometastasis in sentinel lymph node. This can have
      important bearing on deciding the need of adjuvant systemic therapy. A false
      negative result for EMA may be seen in patients with poorly differential cancer.
      Therefore the best policy seems to employ both histopathology and IHC for EMA for
      the comprehensive evaluation of sentinel lymph node in breast cancer.

PMID- 22468059
TI  - Comparison Between Concurrent Chemoradiation Followed by Surgery vs. Surgery for
      Locally Advanced Cancer of Esophagus.
AB  - Surgery is an accepted standard in the treatment of localized stage cancer of
      esophagus. But the ideal approach for locally advanced lesions still remains
      unknown. Patients with locally advanced lesions (cT3-4N1M0) on the basis of CT
      chest were subjected either to primary surgery or to preoperative chemoradiation
      followed by surgery. Major postoperative complications (mortality, anastomotic
      leak and recurrent laryngeal nerve palsy) did not differ in either arm (P = not
      significant). Complete pathological response was achieved in 31.2% cases in
      multimodality arm. Four year overall survival was 10% for whole group. Median
      survival was 14 months and 20 months in surgery and multimodality arm,
      respectively (p = .288). In multimodal arm, there was significant survival
      difference between complete responders and nonresponders (p = .02). For locally
      advanced lesions, surgery alone gives poor outcome and preoperative
      chemoradiation followed by surgery should be considered for complete responders.

PMID- 22468060
TI  - Study of Pulmonary Arterial Pressures and Histopathological Changes in Patients
      Having Congenital Heart Defects with Left-to-Right Shunt.
AB  - Pulmonary arterial hypertension, a common complication in patients with
      congenital heart defects with left-to-right shunt who present late is one of the
      principal determinants of the clinical manifestations, the course and the
      feasibility of surgical repair. The objective is to study the pulmonary arterial
      pressures and the pulmonary histopathological changes in patients having
      congenital heart defects with left-to-right shunt. A total of 20 consecutive
      patients having congenital heart defects with left-to- right shunt who underwent
      surgical correction were studied. Intra-operative mean pulmonary arterial
      pressures were measured before and after surgical correction. Lung biopsy was
      taken to study the histopathological changes of lung parenchyma and vasculature.
      All patients, irrespective of age at the time of surgical repair and the type and
      size of the cardiac defect had raised mean pulmonary arterial pressures that were
      decreased significantly immediately after surgical correction. Pulmonary
      parenchymal changes and vascular changes were noted in 18 and 9 patients
      respectively. The pulmonary vascular changes were significantly correlated with
      the mean pulmonary arterial pressures. The pulmonary parenchymal changes though
      were a consistent finding; not significantly correlated with the mean pulmonary
      arterial pressures.

PMID- 22468061
TI  - Congenital microgastria with limb defect combined with megaduodenum: case report
      and review of literature.
AB  - Congenital microgastria is a rare developmental disorder with only 59 previously
      reported cases. Most of the patients undergoing reconstructive surgery are in
      early infancy, providing gastric augmentation to achieve optimal thrive. The Hunt
      Lawrence pouch is the standard surgical treatment in infancy, but late surgery in
      early adulthood requires different approach. This case demonstrates that
      duodenojejunostomy is safe and effective in the treatment of congenital,
      functional duodenal obstruction in adulthood.

PMID- 22468062
TI  - Ultrasound Doppler evaluation of the pattern of involvement of varicose veins in
      Indian patients.
AB  - Doppler evaluation of lower limb veins was performed to evaluate the pattern of
      involvement of various sites of incompetence in Indian patients with varicose
      veins. A prospective Doppler study of 100 consecutive limbs in patients who
      presented with varicose veins to the vascular surgery department of a tertiary
      care hospital in India. The Clinico-Etiological Anatomical and Pathological
      (CEAP) classification was applied for assessment. Doppler evaluation of both
      superficial and deep venous system of the lower limbs was performed. The data of
      various sites of reflux was analysed to find the patterns of venous involvement
      in the affected patients. Superficial venous reflux was seen in all the patients.
      Deep venous reflux was seen in 50% of the lower limbs examined. Doppler is a
      simple non-invasive test, and is well tolerated by the patients. Deep venous
      reflux is common in Indian population, though it rarely occurs in isolation, and
      is usually associated with superficial reflux.

PMID- 22468063
TI  - An epidemiological study of major surgical procedures in an urban population of
      East delhi.
AB  - Surgery has become an integral part of global health care, with an estimated 234
      million operations performed yearly. The World Bank in 2002 reported that an
      estimated 164 million disability-adjusted life years, representing 11% of the
      entire disease burden, were attributable to surgically treatable conditions. To
      study the prevalence of various surgical operations undergone by individuals in
      their life time, in an urbanized community of Delhi. Cross-sectional study,
      conducted from October 2008 to April 2009 in Vivek Vihar-an urban affluent colony
      in Delhi. A total of 3,043 individuals residing in 622 households were
      interviewed as part of the study. Total number of households with some member
      having ever undergone surgery was 306 (49.2%). 12.3% of our study population (375
      out of 3,043) had undergone one or the other form of major surgical operation in
      their life time. Caesarean section was found to be the most common surgical
      procedure performed. 61.7% surgeries were elective in nature and 81.9% were
      performed in a private hospital. The lifetime prevalence of surgical procedures
      was 1.77% among children, 12.6% among adult males and 15.8% among adult females
      (p < 0.001). It was observed that the expense of surgeries conducted in private
      hospitals was more compared to government. Our findings suggest that surgery
      occurs at a substantial rate, at least among the urban affluent, with most of the
      patients choosing to refer to a private hospital for their surgery.

PMID- 22468064
TI  - Procalcitonin as the biomarker of inflammation in diagnosis of appendicitis in
      pediatric patients and prevention of unnecessary appendectomies.
AB  - Numerous diseases mimic appendicitis, and it is often difficult to rule it out on
      the basis of clinical presentation. Concentration of procalcitonin selectively
      increases in inflammatory conditions and determination of its level can help in
      the diagnosis of acute appendicitis. A prospective, single centre based
      observational study carried out at our tertiary care institute. Twenty eight
      patients were admitted with preliminary diagnosis of acute appendicitis. The
      control group involved around 12 healthy children. Serum Procalcitonin
      concentration was measured in all patients using the 'Immunoluminometric Method'
      (LUMI- Test PCT), besides carrying out clinical examination and other
      investigations. The serums PCT comes out to be a better diagnostic test than
      serum CRP measurement as serum PCT was able to differentiate patients who came
      with abdominal pain but were having normal appendix from the patients who were
      actual cases of acute appendicitis. In patients with histologically confirmed
      acute appendicitis the level of PCT was above the normal value of 0.5 ng/ml in
      most cases. The analysis of procalcitonin in different groups of patients showed
      the serum procalcitonin test having high sensitivity of 95.65% and a specificity
      of about 100% on the basis of histopathological diagnosis of the removed appendix
      taking as the standard. The serum procalcitonin test when combined with reliable
      clinical signs and symptoms is an excellent diagnostic marker of the disease and
      should be done in the patients of pediatric appendicitis so that proper handling
      of the patient can be done and we can prevent unnecessary appendectomies.

PMID- 22468065
TI  - Improvised transumbilical glove port: a cost effective method for single port
      laparoscopic surgery.
AB  - Innovations in technology has changed the traditional laparoscopy to be less
      invasive. Singleport transumbilical laparoscopy has emerged to enhance the
      cosmetic benefits and to decrease the morbidity of the minimally invasive
      surgery. It has further minimized the minimally invasive surgery. However, this
      technique requires a specialized multichannel port (for introducing laparoscope
      and instruments) which is very costly and in fact, is not affordable by the
      majority of the population in a developing country like India. We have improvised
      a single-port access system using readily available materials like surgical
      gloves, towel ring, inner flexible ring and conventional laparoscopic trocars
      with no added cost burden to the patient. We have performed 40 single port
      surgeries using this method without any complications.

PMID- 22468066
TI  - Primary appendiceal mucinous adenocarcinoma.
AB  - Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a
      case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as
      having acute appendicitis. All the routine investigations were within normal
      limit. USG of abdomen showed dilated appendix with little fluid collection
      adjacent to it and no other abnormality was seen which suggested acute
      appendicitis. Appendicectomy was done and excised appendix was sent for
      histopathological examination. Mucinous Adenocarcinoma of the appendix was
      confirmed after histopathological examination. Right hemicolectomy was done as a
      second stage procedure. As some cases are incidentally discovered, this case
      emphasizes that histological examination of all appendicectomy specimens is
      mandatory.

PMID- 22468067
TI  - Mesenteric fibromatosis of the ileocolic area: a case report.
AB  - Fibromatosis is a kind of spindle cell tumor which is characterized by the
      remarkable proliferation and invasive growth of fibrous tissue. It often arises
      from the abdominal wall or the extremities and rarely from the mesentery and
      abdominal organs. The patient was 35 year old female whose major complaints were
      an abdominal mass and pain. She underwent a right hemicolectomy after the tumor
      was confirmed by abdominal ultrasonography and computerized tomography. Hereby
      the pathophysiology, diagnosis and the treatment of the disease is discussed.

PMID- 22468068
TI  - Vesicocutaneous fistula caused by giant vesical calculus.
AB  - Vesicocutaneous fistula is an extremely rare complication of vesical calculus.To
      our knowledge only three cases have been reported in the World literature.
      Because of its rarity, here we report a case of vesicocutaneous fistula caused by
      giant vesical calculus. This is probably the fourth case of vesicocutaneous
      fistula caused by giant vesical calculus.

PMID- 22468069
TI  - Diffuse colonic lipomatosis, presenting as perforation peritonitis and mimicking
      carcinoma colon.
AB  - Lipomas and lipomatosis of colon are rare in clinical practice. We herein report
      a case of diffuse colonic lipomatosis, fifth such case in literature which
      presented as perforation peritonitis, a presentation, never been reported
      earlier. On laparotomy, the findings suggested malignancy and appropriate surgery
      was done. Diffuse Colonic Lipomatosis, a rare and benign condition mimicks
      malignancy and should be kept as a differential diagnosis is unusual cases of
      colonic perforations.

PMID- 22468070
TI  - A large primary hydatid cyst of thigh: a case report.
AB  - Primary hydatid disease of musculoskletal system is rare. A 60 year old woman
      presented with soft swelling in medial aspect of thigh, of long duration which
      was gradually increasing in size. She was initially diagnosed as lipoma of thigh,
      but ultrasonography revealed to be a cystic swelling suggestive of hydatid
      disease. MRI further reinforced the diagnosis. However serologic test (ELISA) was
      negative. Patient was given albendazole preoperatively. The swelling was removed
      en bloc and advised for adjunctive albendazole chemotherapy (15 mg/kg/day) for
      three months.

PMID- 22468071
TI  - Bilateral Psoas Abscess and Extensive Soft Tissue Involvement Due to Late
      Presentation of Pott's Disease of the Spine.
AB  - Pott's disease of the spine with psoas abscess is currently rare form of Extra-
      pulmonary tuberculosis (TB) in the developed countries, however it is still seen
      in areas where TB is endemic. We describe a rare case if not the first (according
      to our knowledge) of bilateral ruptured psoas abscess with extensive tissue
      necrosis and pelvic organs exposure with limited neurological deficit presented
      late in young girl. In this case Pott's disease was associated with extensive
      tissue necrosis exposing pubic bones, urinary bladder and psoas muscle.

PMID- 22468072
TI  - Annular pancreas: a rare cause of duodenal obstruction in adults.
AB  - Annular pancreas is an uncommon congenital anomaly which usually presents itself
      in infants and newborn. Rarely it can present in late adult life with wide range
      of clinical severities thereby making its diagnosis difficult. Pre-operative
      diagnosis is often difficult. CT scan can illustrate the pancreatic tissue
      encircling the duodenum. ERCP and MRCP are useful in outlining the annular
      pancreatic duct. Surgery still remains necessary to confirm diagnosis and
      bypassing the obstructed segment.We report a case of 61 year female presenting
      with duodenal obstruction due to annular pancreas.

PMID- 22468073
TI  - Migration of a GI Foreign Body into Retro Peritoneum Without Peritonitis.
AB  - Reporting an unusual case of a GI foreign body migrating to retro peritoneum
      without peritonitis. A middle aged male patient presented to the outpatient
      department with low back pain, on evaluation there was long slender radio opaque
      foreign body present in the pelvis. Explarotary laparotomy done, surprisingly it
      was found to be a suction canula(metallic) used when undergoing tonsillectomy two
      years ago.

PMID- 22468074
TI  - Pipestem carotids as a marker of vascular insult in graves' disease.
AB  - We present a case of Graves' disease with a image of plain radiograph of neck
      showing bilateral carotid calcifications and briefly discuss the pathophysiology
      of vascular calcification in Graves' disease.

PMID- 22468075
TI  - How could I pass, why should they survive?

PMID- 22468076
TI  - Genetically modified mouse models for the study of nonalcoholic fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin
      resistance, and type 2 diabetes. NAFLD represents a large spectrum of diseases
      ranging from (1) fatty liver (hepatic steatosis); (2) steatosis with inflammation
      and necrosis; to (3) cirrhosis. The animal models to study NAFLD/nonalcoholic
      steatohepatitis (NASH) are extremely useful, as there are still many events to be
      elucidated in the pathology of NASH. The study of the established animal models
      has provided many clues in the pathogenesis of steatosis and steatohepatitis, but
      these remain incompletely understood. The different mouse models can be
      classified in two large groups. The first one includes genetically modified
      (transgenic or knockout) mice that spontaneously develop liver disease, and the
      second one includes mice that acquire the disease after dietary or
      pharmacological manipulation. Although the molecular mechanism leading to the
      development of hepatic steatosis in the pathogenesis of NAFLD is complex,
      genetically modified animal models may be a key for the treatment of NAFLD. Ideal
      animal models for NASH should closely resemble the pathological characteristics
      observed in humans. To date, no single animal model has encompassed the full
      spectrum of human disease progression, but they can imitate particular
      characteristics of human disease. Therefore, it is important that the researchers
      choose the appropriate animal model. This review discusses various genetically
      modified animal models developed and used in research on NAFLD.

PMID- 22468077
TI  - Trends on gastrointestinal bleeding and mortality: where are we standing?
AB  - Bleeding from the gastrointestinal tract and its management are associated with
      significant morbidity and mortality. The predisposing factors that led to the
      occurrence of these hemorrhagic instances are largely linked to the life style of
      the affected persons. Designing a new strategy aimed at educating the publics and
      improving their awareness of the problem could effectively help in eradicating
      this problem with no associated risks and in bringing the mortality rates down to
      almost zero.

PMID- 22468078
TI  - Management of non-variceal upper gastrointestinal tract hemorrhage: controversies
      and areas of uncertainty.
AB  - Upper gastrointestinal tract hemorrhage (UGIH) remains a common presentation
      requiring urgent evaluation and treatment. Accurate assessment, appropriate
      intervention and apt clinical skills are needed for proper management from time
      of presentation to discharge. The advent of pharmacologic acid suppression,
      endoscopic hemostatic techniques, and recognition of Helicobacter pylori as an
      etiologic agent in peptic ulcer disease (PUD) has revolutionized the treatment of
      UGIH. Despite this, acute UGIH still carries considerable rates of morbidity and
      mortality. This review aims to discuss current areas of uncertainty and
      controversy in the management of UGIH. Neoadjuvant proton pump inhibitor (PPI)
      therapy has become standard empiric treatment for UGIH given that PUD is the
      leading cause of non-variceal UGIH, and PPIs are extremely effective at promoting
      ulcer healing. However, neoadjuvant PPI administration has not been shown to
      affect hard clinical outcomes such as rebleeding or mortality. The optimal timing
      of upper endoscopy in UGIH is often debated. Upon completion of volume
      resuscitation and hemodynamic stabilization, upper endoscopy should be performed
      within 24 h in all patients with evidence of UGIH for both diagnostic and
      therapeutic purposes. With rising healthcare cost paramount in today's medical
      landscape, the ability to appropriately triage UGIH patients is of increasing
      value. Upper endoscopy in conjunction with the clinical scenario allows for
      accurate decision making concerning early discharge home in low-risk lesions or
      admission for further monitoring and treatment in higher-risk lesions.
      Concomitant pharmacotherapy with non-steroidal anti-inflammatory drugs (NSAIDs)
      and antiplatelet agents, such as clopidogrel, has a major impact on the etiology,
      severity, and potential treatment of UGIH. Long-term PPI use in patients taking
      chronic NSAIDs or clopidogrel is discussed thoroughly in this review.

PMID- 22468079
TI  - Treatment of portal hypertension.
AB  - Portal hypertension is the main complication of cirrhosis and is defined as an
      hepatic venous pressure gradient (HVPG) of more than 5 mmHg. Clinically
      significant portal hypertension is defined as HVPG of 10 mmHg or more.
      Development of gastroesophageal varices and variceal hemorrhage are the most
      direct consequence of portal hypertension. Over the last decades significant
      advancements in the field have led to standard treatment options. These clinical
      recommendations have evolved mostly as a result of randomized controlled trials
      and consensus conferences among experts where existing evidence has been reviewed
      and future goals for research and practice guidelines have been proposed.
      Management of varices/variceal hemorrhage is based on the clinical stage of
      portal hypertension. No specific treatment has shown to prevent the formation of
      varices. Prevention of first variceal hemorrhage depends on the
      size/characteristics of varices. In patients with small varices and high risk of
      bleeding, non-selective beta-blockers are recommended, while patients with
      medium/large varices can be treated with either beta-blockers or esophageal band
      ligation. Standard of care for acute variceal hemorrhage consists of vasoactive
      drugs, endoscopic band ligation and antibiotics prophylaxis. Transjugular
      intrahepatic portosystemic shunt (TIPS) is reserved for those who fail standard
      of care or for patients who are likely to fail ("early TIPS"). Prevention of
      recurrent variceal hemorrhage consists of the combination of beta-blockers and
      endoscopic band ligation.

PMID- 22468080
TI  - Management of portal hypertension in children.
AB  - Portal hypertension can be caused by a wide variety of conditions. It frequently
      presents with bleeding from esophageal varices. The approach to acute variceal
      hemorrhage in children is a stepwise progression from least invasive to most
      invasive. Management of acute variceal bleeding is straightforward. But data on
      primary prophylaxis and long term management prevention of recurrent variceal
      bleeding in children is scarce, therefore prospective multicenter trials are
      needed to establish best practices.

PMID- 22468081
TI  - Pros and cons of colonoscopy in management of acute lower gastrointestinal
      bleeding.
AB  - Acute lower gastrointestinal bleeding (LGIB) is a frequent gastrointestinal cause
      of hospitalization, particularly in the elderly, and its incidence appears to be
      on the rise. Endoscopic and radiographic measures are available for the
      evaluation and treatment of LGIB including flexible sigmoidoscopy, colonoscopy,
      angiography, radionuclide scintigraphy and multi-detector row computed
      tomography. Although no modality has emerged as the gold standard in the
      management of LGIB, colonoscopy is the current preferred initial test for the
      majority of the patients presenting with hematochezia felt to be from a colon
      source. Colonoscopy has the ability to diagnose all sources of bleeding from the
      colon and, unlike the radiologic modalities, does not require active bleeding at
      the time of the examination. In addition, therapeutic interventions such as
      cautery and endoclips can be applied to achieve hemostasis and prevent recurrent
      bleeding. Studies suggest that colonoscopy, particularly when performed early in
      the hospitalization, can decrease hospital length of stay, rebleeding and the
      need for surgery. However, results from available small trials are conflicting
      and larger, multicenter studies are needed. Compared to other management options,
      colonoscopy is a safe procedure with complications reported in less than 2% of
      patients, including those undergoing urgent examinations. The requirement of
      bowel preparation (typically 4 or more liters of polyethylene glycol), the
      logistical complexity of coordinating after-hours colonoscopy, and the low
      prevalence of stigmata of hemorrhage complicate the use of colonoscopy for LGIB,
      particularly in urgent situations. This review discusses the above advantages and
      disadvantages of colonoscopy in the management of acute lower gastrointestinal
      bleeding in further detail.

PMID- 22468082
TI  - Angiographic evaluation and management of acute gastrointestinal hemorrhage.
AB  - Although most cases of acute nonvariceal gastrointestinal hemorrhage either
      spontaneously resolve or respond to medical management or endoscopic treatment,
      there are still a significant number of patients who require emergency
      angiography and transcatheter treatment. Evaluation with noninvasive imaging such
      as nuclear scintigraphy or computed tomography may localize the bleeding source
      and/or confirm active hemorrhage prior to angiography. Any angiographic
      evaluation should begin with selective catheterization of the artery supplying
      the most likely site of bleeding, as determined by the available clinical,
      endoscopic and imaging data. If a hemorrhage source is identified, superselective
      catheterization followed by transcatheter microcoil embolization is usually the
      most effective means of successfully controlling hemorrhage while minimizing
      potential complications. This is now well-recognized as a viable and safe
      alternative to emergency surgery. In selected situations transcatheter intra
      arterial infusion of vasopressin may also be useful in controlling acute
      gastrointestinal bleeding. One must be aware of the various side effects and
      potential complications associated with this treatment, however, and recognize
      the high re-bleeding rate. In this article we review the current role of
      angiography, transcatheter arterial embolization and infusion therapy in the
      evaluation and management of nonvariceal gastrointestinal hemorrhage.

PMID- 22468083
TI  - Management of acute nonvariceal upper gastrointestinal bleeding: current policies
      and future perspectives.
AB  - Acute upper gastrointestinal bleeding (UGIB) is a gastroenterological emergency
      with a mortality of 6%-13%. The vast majority of these bleeds are due to peptic
      ulcers. Nonsteroidal anti-inflammatory drugs and Helicobacter pylori are the main
      risk factors for peptic ulcer disease. Endoscopy has become the mainstay for
      diagnosis and treatment of acute UGIB, and is recommended within 24 h of
      presentation. Proton pump inhibitor (PPI) administration before endoscopy can
      downstage the bleeding lesion and reduce the need for endoscopic therapy, but has
      no effect on rebleeding, mortality and need for surgery. Endoscopic therapy
      should be undertaken for ulcers with high-risk stigmata, to reduce the risk of
      rebleeding. This can be done with a variety of modalities. High-dose PPI
      administration after endoscopy can prevent rebleeding and reduce the need for
      further intervention and mortality, particularly in patients with high-risk
      stigmata.

PMID- 22468084
TI  - Expression of HER2 and bradykinin B1 receptors in precursor lesions of
      gallbladder carcinoma.
AB  - AIM: To determine the expression of HER2 and bradykinin B(1) receptors (B(1)R) in
      the two pathogenic models of gallbladder cancer: the metaplasia-dysplasia
      carcinoma and the adenoma-carcinoma pathways. METHODS: Receptor proteins were
      visualized by immunohistochemistry on 5-MUm sections of paraffin-embedded tissue.
      Expression of both receptors was studied in biopsy samples from 92 patients (6
      males and 86 females; age ranging from 28 to 86 years, mean 56 years). High HER2
      expression in specimens was additionally investigated by fluorescence in situ
      hybridization. Cell proliferation in each sample was assessed by using the Ki-67
      proliferation marker. RESULTS: HER2 receptor protein was absent in adenomas and
      in normal gallbladder epithelium. On the contrary, there was intense staining for
      HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia
      (22/24; 91.7%) and carcinoma in situ (9/10; 90%), the lesions that displayed a
      significantly high proliferation index. Protein up-regulation of HER2 in the
      epithelium with metaplasia or carcinoma in situ was not accompanied by HER2 gene
      amplification. A similar result was observed in invasive carcinomas (0/12). The
      B(1)R distribution pattern mirrored that of HER2 except that B(1)R was
      additionally observed in the adenomas. The B(1)R appeared either as cytoplasmic
      dots or labeling on the apical cell membrane of the cells composing the epithelia
      with intestinal metaplasia (24/24; 100%) and carcinoma in situ (10/10; 100%) and
      in the epithelial cells of adenomas. In contrast, both HER2 (4/12; 33%) and B(1)R
      (1/12; 8.3%) showed a low expression in invasive gallbladder carcinomas.
      CONCLUSION: The up-regulation of HER2 and B(1)R in precursor lesions of
      gallbladder carcinoma suggests cross-talk between these two receptors that may be
      of importance in the modulation of cell proliferation in gallbladder
      carcinogenesis.

PMID- 22468085
TI  - Proteomic analysis of gastric cancer and immunoblot validation of potential
      biomarkers.
AB  - AIM: To search for and validate differentially expressed proteins in patients
      with gastric adenocarcinoma. METHODS: We used two-dimensional gel electrophoresis
      and mass spectrometry to search for differentially expressed proteins in patients
      with gastric adenocarcinoma. A set of proteins was validated with immunoblotting.
      RESULTS: We identified 30 different proteins involved in various biological
      processes: metabolism, development, death, response to stress, cell cycle, cell
      communication, transport, and cell motility. Eight proteins were chosen for
      further validation by immunoblotting. Our results show that gastrokine-1, 39S
      ribosomal protein L12 (mitochondrial precursor), plasma cell-induced resident
      endoplasmic reticulum protein, and glutathione S-transferase mu 3 were
      significantly underexpressed in gastric adenocarcinoma relative to adjacent non
      tumor tissue samples. On the other hand, septin-2, ubiquitin-conjugating enzyme
      E2 N, and transaldolase were significantly overexpressed. Translationally
      controlled tumor protein was shown to be differentially expressed only in
      patients with cancer of the gastric cardia/esophageal border. CONCLUSION: This
      work presents a set of possible diagnostic biomarkers, validated for the first
      time. It might contribute to the efforts of understanding gastric cancer
      carcinogenesis.

PMID- 22468086
TI  - High-dose infliximab for treatment of pediatric ulcerative colitis: a survey of
      clinical practice.
AB  - AIM: To assess attitudes and trends regarding the use of high-dose infliximab
      among pediatric gastroenterologists for treatment of pediatric ulcerative colitis
      (UC). METHODS: A 19-item survey was distributed to subscribers of the pediatric
      gastroenterology (PEDSGI) listserv. Responses were submitted anonymously and
      results compiled in a secure website. RESULTS: A total of 113 subscribers (88%
      based in the United States) responded (101 pediatric gastroenterology attendings
      and 12 pediatric gastroenterology fellows). There were 46% in academic medical
      institutions and 39% in hospital-based practices. The majority (91%) were
      treating >10 patients with UC; 13% were treating >100 patients with UC; 91% had
      prescribed infliximab (IFX) 5 mg/kg for UC; 72% had prescribed IFX 10 mg/kg for
      UC. Using a 5-point Likert scale, factors that influenced the decision not to
      increase IFX dosing in patients with UC included: "improvement on initial dose of
      IFX" (mean: 3.88) and "decision to move to colectomy" (3.69). Lowest mean Likert
      scores were: "lack of guidelines or literature regarding increased IFX dosing"
      (1.96) and "insurance authorization or other insurance issues" (2.34). "Insurance
      authorization or other insurance issues" was identified by 39% as at least
      somewhat of a factor (Likert score >= 3) in their decision not to increase the
      IFX dose. IFX 10 mg/kg was more commonly used for the treatment of pediatric UC
      among responders based in the United States (75/100) compared to non-United
      States responders (6/13, P = 0.047). Induction of remission was reported by 78%
      of all responders and 81% reported maintenance of remission with IFX 10 mg/kg.
      One responder reported one death with IFX 10 mg/kg. CONCLUSION: IFX 10 mg/kg is
      more commonly used in the United States to treat pediatric UC. Efficacy and
      safety data are required to avoid insurance barriers for its use.

PMID- 22468087
TI  - Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric
      cancer in a Brazilian population.
AB  - AIM: To investigate toll-like receptor 2 (TLR2) -196 to -174 del, and TLR4
      (+896A/G rs4986790 and +1196C/T rs4986791) polymorphisms at risk of chronic
      gastritis and gastric cancer in a Brazilian population and association of gastric
      lesions with risk factors such as smoking, alcohol intake and Helicobacter pylori
      infection. METHODS: In this case-control study, polymorphism at TLR2 -196 to -174
      del was investigated by using the allele-specific polymerase chain reaction (PCR)
      method, while the PCR-restriction fragment length polymorphism technique was
      carried out to identify the TLR4 (rs4986790 and rs4986791) genotypes in 607
      Brazilian individuals (208 with chronic gastritis-CG, 174 with gastric cancer-GC
      and 225 controls -C). RESULTS: The single nucleotide polymorphisms TLR4+1196C/T
      was not associated with risk of chronic gastritis or gastric cancer and the
      homozygous genotypes TLR4+896GG and TLR4+1196TT were absent in the studied
      population. However, the frequency of TLR2 -196 to -174 ins/del + del/del and
      TLR4+896AG genotypes was significantly higher (P < 0.01 and P = 0.01,
      respectively) in the cancer group (33.4% and 11.5%, respectively) than in the
      control group (16.9% and 4.5%, respectively). It was also observed that the G-C
      haplotype of the TLR4+896A/G+1196C/T (P = 0.02) and the combination of variant
      alleles of the TLR2/TLR4+896G (P = 0.02) are associated with susceptibility to
      gastric cancer. In addition, the multiple logistic regression showed that male
      gender [odds ratio (OR) = 2.70; 95% CI: 1.66-4.41; P < 0.01], alcohol intake (OR
      = 2.93; 95% CI: 1.76-4.87; P < 0.01), TLR2 -196 to -174 del (OR = 2.64; 95% CI:
      1.56-4.44; P < 0.01) and TLR4+896G (OR = 3.19; 95% CI: 1.34- 7.61; P < 0.01)
      polymorphisms were associated with a higher susceptibility to developing this
      neoplasm. CONCLUSION: Our data indicate that TLR2 -196 to -174 del and TLR4+896G
      may increase the risk of gastric cancer in a Brazilian population.

PMID- 22468088
TI  - Adenoma incidence decreases under the effect of polypectomy.
AB  - AIM: To investigate whether, under the influence of polypectomy, the incidence of
      adenoma decreases with age. METHODS: Consecutive patients with colonic adenomas
      identified at index colonoscopy were retrospectively selected if they had
      undergone three or more complete colonoscopies, at least 24 mo apart. Patients
      who had any first-degree relative with colorectal cancer were excluded. Data
      regarding number of adenomas at each colonoscopy, their location, size and
      histological classification were recorded. The monthly incidence density of
      adenomas after the index examination was estimated for the study population, by
      using the person-years method. Baseline adenomas were excluded from incidence
      calculations but their characteristics were correlated with recurrence at follow
      up, using the chi(2) test. RESULTS: One hundred and fifty-six patients were
      included (109 male, mean age at index colonoscopy 56.8 +/- 10.3 years), with
      follow-up that ranged from 48 to 232 mo. No significant correlations were
      observed between the number, the presence of villous component, or the size of
      adenomas at index colonoscopy and the presence of adenomas at subsequent
      colonoscopies (P = 0.49, 0.12 and 0.78, respectively). The incidence of colonic
      adenomas was observed to decay from 1.4% person-months at the beginning of the
      study to values close to 0%, at 12 years after index colonoscopy. CONCLUSION: Our
      results suggest the sporadic formation of adenomas occurs within a discrete
      period and that, when these adenomas are removed, all neoplasia-prone clones may
      be extinguished.

PMID- 22468089
TI  - CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node
      metastasis and poor prognosis.
AB  - AIM: To investigate how a complex network of CC chemokine ligands (CCLs) and
      their receptors influence the progression of tumor and metastasis. METHODS: In
      the present study, we used immunohistochemistry to examine the expression of
      CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues.
      We analyzed their correlation with tumor metastasis, clinicopathologic parameters
      and clinical outcome. RESULTS: We found that the higher expression of CCL7 and
      CCL21 in cancer tissues than in normal tissues was significantly correlated with
      advanced depth of wall invasion, lymph node metastasis and higher tumor node
      metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and
      CCL21 overexpression in cancer tissues was correlated with poor prognosis.
      CONCLUSION: These results suggest that overexpression of these two CC chemokine
      ligands is associated with tumor metastasis and serves as a prognostic factor in
      patients with gastric cancer.

PMID- 22468090
TI  - Bacterial flora concurrent with Helicobacter pylori in the stomach of patients
      with upper gastrointestinal diseases.
AB  - AIM: To investigate the non-Helicobacter pylori (H. pylori) bacterial flora
      concurrent with H. pylori infection. METHODS: A total of 103 gastric biopsy
      specimens from H. pylori positive patients were selected for bacterial culture.
      All the non-H. pylori bacterial isolates were identified by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: A
      total of 201 non-H. pylori bacterial isolates were cultivated from 67 (65.0%) of
      the 103 gastric samples, including 153 isolates identified successfully at
      species level and 48 at genus level by MALDI-TOF MS. The dominant species were
      Streptococcus, Neisseria, Rothia and Staphylococcus, which differed from the
      predominantly acid resistant species reported previously in healthy volunteers.
      The prevalence of non-H. pylori bacteria was higher in non-ulcer dyspepsia group
      than in gastric ulcer group (100% vs 42.9%, P < 0.001). Six bacterial species
      with urease activity (Staphylococcus epidermidis, Staphylococcus warneri,
      Staphylococcus capitis, Staphylococcus aureus, Brevibacterium spp. and Klebsiella
      pneumoniae) were also isolated. CONCLUSION: There is a high prevalence of the non
      H. pylori bacteria concurrent with H. pylori infection, and the non-H. pylori
      bacteria may also play important as-yet-undiscovered roles in the pathogenesis of
      stomach disorders.

PMID- 22468091
TI  - Gastric cancer incidence and mortality in Zhuanghe, China, between 2005 and 2010.
AB  - AIM: To investigate the incidence and mortality of gastric cancer (GC) in
      Zhuanghe region, northeast China and the influencing factors for their changing
      trends. METHODS: All new cancer cases and deaths registered from 2005 to 2010 in
      Zhuanghe County were reviewed. The annual GC cases, constituent ratio, crude
      rates, age-standardized rates, their sex and age distribution and temporal trends
      were assessed. The method of annual percentage change (APC) was used to estimate
      the trends of GC. RESULTS: Altogether 2634 new cases of GC and 1722 related
      deaths were registered, which accounted for 21.04% and 19.13% of all cancer
      related incidence and deaths, respectively. The age-standardized incidence rate
      steadily decreased from 57.48 in 2005 to 44.53 in 2010 per 10(5) males, and from
      18.13 to 14.70 per 10(5) females, resulting in a APC of -5.81% for males and 
      2.89% for females over the entire period. The magnitude of APC in GC mortality
      amounted to -11.09% and -15.23%, respectively, as the age-standardized mortality
      rate steadily decreased from 42.08 in 2005 to 23.71 in 2010 per 10(5) males, and
      from 23.86 to 10.78 per 10(5) females. Females had a significantly lower
      incidence (a male/female ratio 2.80, P < 0.001) and mortality (a male/female
      ratio 2.30, P < 0.001). In both genders, the peak incidence and mortality
      occurred in the 80-84 years age group. The age-standardized mortality/incidence
      ratio also decreased from the peak of 0.73 in 2005 to 0.53 in 2010 for males, and
      from 1.32 to 0.73 for females. CONCLUSION: Encouraging declines of incidence and
      mortality of GC were observed in Zhuanghe region between 2005 and 2010, possibly
      due to the economic development and efficient GC control strategies.

PMID- 22468092
TI  - Esophageal duplication cysts: endosonographic findings in asymptomatic patients.
AB  - Esophageal duplication cysts are rare inherited lesions usually diagnosed in
      early childhood. Most of them are found in the mediastinum and manifest
      themselves as separate masses along or in continuity with the native esophagus.
      Their prevalence remains unknown and they are treated either surgically or
      endoscopically. In this report we describe a series of four adult patients in
      whom esophageal duplication cysts were localised intramurally as masses pressing
      on the esophageal lumen and who were diagnosed with endoscopic ultrasonography.
      All patients were initially referred to other centres for upper
      gastroduodenoscopy due to non-specific dyspeptic symptoms. After finding
      suspicious lesions in the esophagus their endoscopists referred them for
      endoscopic ultrasound examination at our centre. In two of the cases lesions
      mimicked esophageal varices and the other two submucosal tumours. In all four
      patients endoscopic ultrasonography has shown esophageal duplication cysts.
      Patients had no symptoms suggesting disease of the esophagus and required no
      treatment. As the true prevalence of esophageal cysts is unknown, it is very
      likely that in many patients, like in these four described by us, they may cause
      no symptoms, remain undetected and require no intervention. Increasing
      availability of new diagnostic modalities such as endoscopic ultrasonography may
      change the current view regarding the prevalence of esophageal duplication cysts
      and prove that they may, in fact, not be such rare findings.

PMID- 22468093
TI  - Tumors with macroscopic bile duct thrombi in non-HCC patients: dynamic multi
      phase MSCT findings.
AB  - Non-hepatocellular carcinoma (non-HCC) with macroscopic bile duct tumor thrombus
      (BDTT) formation is rare, few radiological studies have been reported. In this
      case report, we retrospectively analyzed the imaging findings of three cases of
      non-HCC with macroscopic BDTT on dynamic enhanced multislice computed tomography
      (MSCT) scan. One case of primary hepatic carcinosarcoma was presented as a
      solitary, large well-defined tumor with significant necrotic changes. One case of
      liver metastasis from colon cancer was presented as a lobulated, large ill
      defined tumor. One case of intraductal oncocytic papillary neoplasm involved the
      entire pancreas, presented as a cystic and solid mass with multilocular changes
      (the individual loculi were less than 5.0 mm in diameter). The bile duct was
      dilated due to expansible growth of the BDTT in all three patients. The BDTT was
      contiguous with hepatic or pancreatic tumor, and both of them showed the same
      enhancement patterns on dynamic contrast-enhanced computed tomography scan: early
      enhancement in the hepatic arterial phase and a quick wash-out of contrast agent
      in the portal and equilibrium phases. Macroscopic BDTT in non-HCC patient is
      rare, dynamic enhanced MSCT scan may be valuable in the diagnosis of non-HCC with
      BDTT.

PMID- 22468094
TI  - Prospective controlled protocol for three months steroid withdrawal with
      tacrolimus, basiliximab, and mycophenolate mofetil in renal transplant
      recipients.
AB  - During the past few years, new immunosuppressants, such as tacrolimus,
      mycophenolate mofetil (MMF) and basiliximab, have been shown to successfully
      decrease the incidence of acute rejection, possibly acting as potent substrates
      for safe steroid withdrawal. Therefore, clinical outcome of 3 months steroid
      withdrawal, while using the above immunosuppressants, was analyzed. Clinical
      trial registry No. was NCT 01550445. Thirty de novo renal transplant recipients
      were enrolled, and prednisolone was slowly withdrawn 3 months post
      transplantation by 2.5 mg at every two weeks, until 8 weeks. During steroid
      withdrawal, 10 patients (30.0%) discontinued the protocol and they were
      maintained on steroid treatment. Among 20 steroid free patients, 8 patients
      (40.0%) re-started the steroid within 12 months post-transplantation. By the
      study endpoint, 12 (40%) recipients did not take steroid and survival of patients
      and grafts was 100%. In conclusion, in kidney transplant patients, 3 months
      steroid withdrawal while taking tacrolimus, basiliximab and mycophenolate mofetil
      was not associated with increased mortality or graft loss. Despite various causes
      of failure of steroid withdrawal during the follow-up period, it is a strategy
      well advised for kidney transplant recipients with regard to long-term steroid
      related complications.

PMID- 22468095
TI  - Potential association of DCBLD2 polymorphisms with fall rates of FEV(1) by
      aspirin provocation in Korean asthmatics.
AB  - Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome
      characterized by chronic rhinosinusitis with nasal polyposis and aspirin
      hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and
      eosinophilic inflammation. Recently, it has been reported that the expression of
      discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in
      lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a
      component of activator protein-2 (AP-2) that is known to regulate IL-8 production
      in human lung fibroblasts and epithelial cells. To investigate the associations
      between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163
      AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these
      variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616,
      rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with
      susceptibility to AERD. In further analysis, this study reveals significant
      associations between the SNPs or haplotypes and the percentage of forced
      expiratory volume in one second (FEV(1)) decline following aspirin challenge
      using multiple linear regression analysis. Furthermore, a non-synonymous SNP
      rs16840208 (Asp723Asn) shows a strong association with FEV(1) decline in AERD
      patients. Although further studies for the non-synonymous Asp723Asn variation are
      needed, our findings suggest that DCBLD2 could be related to FEV(1)-related
      phenotypes in asthmatics.

PMID- 22468096
TI  - Changes in sensitization rate to weed allergens in children with increased weeds
      pollen counts in Seoul metropolitan area.
AB  - The prevalence of allergic diseases in children has increased for several
      decades. We evaluated the correlation between pollen count of weeds and their
      sensitization rate in Seoul, 1997-2009. Airborne particles carrying allergens
      were collected daily from 3 stations around Seoul. Skin prick tests to pollen
      were performed on children with allergic diseases. Ragweed pollen gradually
      increased between 1999 and 2005, decreased after 2005 and plateaued until 2009
      (peak counts, 67 in 2003, 145 in 2005 and 83 grains/m(3)/day in 2007). Japanese
      hop pollen increased between 2002 and 2009 (peak counts, 212 in 2006 and 492
      grains/m(3)/day in 2009). Sensitization rates to weed pollen, especially ragweed
      and Japanese hop in children with allergic diseases, increased annually (ragweed,
      2.2% in 2000 and 2.8% in 2002; Japanese hop, 1.4% in 2000 and 1.9% in 2002). The
      age for sensitization to pollen gradually became younger since 2000 (4 to 6 yr of
      age, 3.5% in 1997 and 6.2% in 2009; 7 to 9 yr of age, 4.2% in 1997 and 6.4% in
      2009). In conclusion, sensitization rates for weed pollens increase in Korean
      children given increasing pollen counts of ragweed and Japanese hop.

PMID- 22468097
TI  - Comparison of clinical outcome and cost-effectiveness after various preoperative
      biliary drainage methods in periampullary cancer with obstructive jaundice.
AB  - The aim of this study was to compare the clinical outcome and cost-effectiveness
      of preoperative biliary drainage (BD) methods in periampullary cancer, and to
      suggest guidelines for selecting the appropriate preoperative BD method. Between
      October 2004 and August 2010, 211 patients underwent pancreatoduodenectomy after
      preoperative BD. Clinical outcome and cost-effectiveness of the preoperative BD
      methods were compared based on the final drainage method used and on intention-to
      treat analysis. There was no significant difference in drainage duration between
      percutaneous transhepatic biliary drainage (PTBD) and endoscopic BD groups (14.2
      vs 16.6 days, respectively; P = 0.121) but daily diminution of serum bilirubin
      level was higher in the PTBD group (0.7 vs 0.6 mg/dL/day, respectively; P =
      0.041). Based on intention-to-treat analysis, drainage duration was shorter (13.2
      vs 16.5 days, respectively; P = 0.049), daily diminution of serum bilirubin level
      was higher (0.7 vs 0.6 mg/dL/day, respectively; P = 0.041). Medical care cost was
      lower (14.2 vs 15.7 * 10(3) USD, respectively; P = 0.040) in the PTBD group than
      in the endoscopic BD group. When selecting the preoperative BD method,
      practitioners should consider that PTBD is more cost-effective and safer than
      endoscopic BD.

PMID- 22468098
TI  - Iron overload during follow-up after tandem high-dose chemotherapy and autologous
      stem cell transplantation in patients with high-risk neuroblastoma.
AB  - Multiple RBC transfusions inevitably lead to a state of iron overload before and
      after high-dose chemotherapy and autologous stem cell transplantation
      (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains
      unknown. Therefore, we investigated post-SCT ferritin levels, factors
      contributing to its sustained levels, and organ functions affected by iron
      overload in 49 children with high-risk neuroblastoma who underwent tandem
      HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT
      follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at
      1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine
      (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT
      transfusion amount corresponded to increased ferritin levels at 1 yr after the
      second HDCT/autoSCT (P < 0.001). A lower CD34(+) cell count was associated with a
      greater need of RBC transfusion, which in turn led to a higher serum ferritin
      level at 1 yr after HDCT/autoSCT. The number of CD34(+) cells transplanted was an
      independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P =
      0.019). Consequently, CD34(+) cells should be transplanted as many as possible to
      prevent the sustained iron overload after tandem HDCT/autoSCT and consequent
      adverse effects.

PMID- 22468099
TI  - Relation between anemia and vulnerable coronary plaque components in patients
      with acute coronary syndrome: virtual histology-intravascular ultrasound
      analysis.
AB  - The aim of the present study was to evaluate the plaque components and the
      predictors of thin-cap fibroatheroma (TCFA) in anemic patients with acute
      coronary syndrome using virtual histology-intravascular ultrasound (VH-IVUS).
      Anemia was defined according to criteria of the World Health Organization, (i.e.
      , hemoglobin levels < 13 g/dL in men and < 12 g/dL in women) and we compared VH
      IVUS findings between anemia group (171 patients, 260 lesions) and non-anemia
      group (569 patients, 881 lesions). Anemia group had greater % necrotic core (NC)
      volume (21% +/- 9% vs 19% +/- 9%, P = 0.001) compared with non-anemia group.
      Hemoglobin level correlated negatively with absolute NC volume (r = -0.235, P <
      0.001) and %NC volume (r = -0.209, P < 0.001). Independent predictors of TCFA by
      multivariate analysis were diabetes mellitus (odds ratio [OR], 2.213; 95%
      confidence interval [CI], 1.403-3.612, P = 0.006), high-sensitivity C-reactive
      protein (OR, 1.143; 95% CI, 1.058-1.304, P = 0.012), microalbuminuria (albumin
      levels of 30 to 300 mg/g of creatinine) (OR, 2.124; 95% CI, 1.041-3.214, P =
      0.018), and anemia (OR: 2.112; 95% CI 1.022-3.208, P = 0.028). VH-IVUS analysis
      demonstrates that anemia at the time of clinical presentation is associated with
      vulnerable plaque component in patients with acute coronary syndrome.

PMID- 22468100
TI  - Low resistin level is associated with poor hospitalization-free survival in
      hemodialysis patients.
AB  - Malnutrition and inflammation are related to high rates of morbidity and
      mortality in hemodialysis patients. Resistin is associated with nutrition and
      inflammation. We attempted to determine whether resistin levels may predict
      clinical outcomes in hemodialysis patients. We conducted a prospective evaluation
      of 100 outpatients on hemodialysis in a single dialysis center (male, 46%; mean
      age, 53.7 +/- 16.4 yr). We stratified the patients into 4 groups according to
      quartiles of serum resistin levels. During the 18-month observational period,
      patients with the lowest quartile of serum resistin levels had poor
      hospitalization-free survival (log rank test, P = 0.016). After adjustment of all
      co-variables, patients with the lowest quartile of serum resistin levels had poor
      hospitalization-free survival, compared with reference resistin levels. Higher
      levels of interleukin-6 were an independent predictor of poor hospitalization
      free survival. In contrast, serum resistin levels were not correlated with
      interleukin-6 levels. The current data showed that low resistin levels may
      independently predict poor hospitalization free survival in hemodialysis
      patients.

PMID- 22468101
TI  - Effect of interleukin-18 gene polymorphisms on sensitization to wheat flour in
      bakery workers.
AB  - Lower respiratory symptoms in bakery workers may be induced by wheat flour and
      endotoxins. We hypothesized that endotoxins from wheat flour may stimulate innate
      immunity and that interleukin-18 (IL-18) gene polymorphisms may affect their
      regulatory role in innate immune responses to endotoxins. To investigate the
      genetic contribution of IL-18 to sensitization to wheat flour, we performed a
      genetic association study of IL-18 in Korean bakery workers. A total of 373
      bakery workers undertook a questionnaire regarding work-related symptoms. Skin
      prick tests with common and occupational allergens were performed and specific
      antibodies to wheat flour were measured by ELISA. Three polymorphisms of the IL
      18 gene (-607A/C, -137G/C, 8674C/G) were genotyped, and the functional effects of
      the polymorphisms were analyzed using the luciferase reporter assay. Genotypes of
      -137G/C (GC or CC) and haplotype ht3 [ACC] showed a significant association with
      the rate of sensitization to wheat flour. Luciferase activity assay indicated ht3
      [AC] as a low transcript haplotype. In conclusion, the regulatory role of IL-18
      in lipopolysaccharide-induced responses in bakery workers may be affected by this
      polymorphism, thus contributing to the development of sensitization to wheat
      flour and work-related respiratory symptoms.

PMID- 22468102
TI  - Associations between screen-based sedentary behavior and cardiovascular disease
      risk factors in Korean youth.
AB  - The purposes of this study were to: 1) describe the patterns of screen-based
      sedentary behaviors, and 2) examine the association between screen-based
      sedentary behavior and cardiovascular disease (CVD) risk factors in
      representative Korean children and adolescents, aged 12 to 18 yr, in the Korean
      National Health and Nutrition Examination Survey. Screen-based sedentary behavior
      was measured using self-report questionnaires that included items for time spent
      watching TV and playing PC/video games. Physical activity was measured using
      items for frequency and duration of moderate-to-vigorous physical activity
      (MVPA). CVD risk factors such as body mass index (BMI), waist circumference, LDL
      cholesterol, HDL cholesterol, total cholesterol, triglycerides, glucose, systolic
      blood pressure, and diastolic blood pressure were measured. Boys spent more time
      playing PC/video games, and girls spent more time watching TV. After adjusting
      for age, gender, annual household income, and MVPA, an additional hour of
      watching TV was significantly associated with the risk of overweight (OR 1.17
      [95% CI 1.03-1.33]), high abdominal adiposity (OR 1.27 [1.06-1.51]), and low HDL
      cholesterol (OR 1.27 [1.10-1.47]). An additional hour spent playing PC/video
      games also increased the risk of high abdominal adiposity (OR 1.20 [1.03-1.40]).
      Prospective observations and interventions are needed to determine causal
      relationships between screen-based sedentary behavior and CVD risk profiles in
      Korean youth.

PMID- 22468103
TI  - Effects of postnatal dexamethasone or hydrocortisone in a rat model of antenatal
      lipopolysaccharide and neonatal hyperoxia exposure.
AB  - The aim of our study was to investigate the differential effects of dexamethasone
      (DXM) and hydrocortisone (HCS) on somatic growth and postnatal lung development
      in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was
      induced by administering intra-amniotic lipopolysaccharide (LPS) and postnatal
      hyperoxia. The rats were treated with a 6-day (D1-D6) tapering course of DXM
      (starting dose 0.5 mg/kg/day), HCS (starting dose 2 mg/kg/day), or an equivalent
      volume of normal saline. DXM treatment in a rat model of BPD induced by LPS and
      hyperoxia was also associated with a more profound weight loss compared to
      control and LPS + O(2) groups not exposed to corticosteroid, whereas HCS
      treatment affected body weight only slightly. Examination of lung morphology
      showed worse mean cord length in both LPS + O(2) + DXM and LPS + O(2) + HCS
      groups as compared to the LPS + O(2) alone group, and the LPS + O(2) + DXM group
      had thicker alveolar walls than the LPS + O(2) group at day 14. The HCS treatment
      was not significantly associated with aberrant alveolar wall thickening and
      retarded somatic growth. The use of postnatal DXM or HCS in a rat model of BPD
      induced by intra-amniotic LPS and postnatal hyperoxia appeared detrimental to
      lung growth, but there was less effect in the case of HCS. These findings suggest
      that effect of HCS on somatic growth and pulmonary outcome may be better
      tolerated in neonates for preventing and/or treating BPD.

PMID- 22468104
TI  - Neurologic complications and outcomes of pandemic (H1N1) 2009 in Korean children.
AB  - Neurologic complications of children with influenza A H1N1 2009 pandemic,
      diagnosed in two consecutive influenza seasons were retrospectively reviewed to
      seek better outcomes in future outbreaks. Patient demographics, clinical
      manifestations and neurologic outcomes were reviewed. A total of 1,389 children
      were diagnosed with influenza A H1N1 by real-time reverse transcriptase
      polymerase chain reaction. Of these, 23 (1.7%) patients had neurologic
      involvement. Their mean age was 5.9 +/- 3.6 yr (range, 6 months to 11 yr) and 16
      (69.9%) were boys. None of the 23 patients had been vaccinated for influenza A
      H1N1 and seasonal influenzas. Twenty-two of the 23 patients presented with
      seizures. Clinical features included febrile convulsion (n = 19), afebrile
      convulsion (n = 1), aseptic meningitis (n = 1), encephalopathy (n = 1), and acute
      necrotizing encephalopathy (n = 1). They all were treated with Oseltamivir twice
      daily for 5 days immediately after nasal and throat swab testing. Twenty-one of
      the subjects recovered fully, but the youngest two infants experienced severe
      neurological sequelae. The results indicate that neurologic complications
      associated with influenza A H1N1 2009 pandemic were mostly mild, but rarely were
      serious. Prompt intervention leads to a better outcome and vaccination may
      prevent the disease, thus staving off serious neurological complications
      following influenza, especially in young infants.

PMID- 22468105
TI  - Characteristics of hospitalized children with 2009 pandemic influenza A (H1N1): a
      multicenter study in Korea.
AB  - The majority of Korean patients with pandemic influenza A (H1N1) during the 2009
      epidemic were under 20 yr of age. The limited data on the clinical
      characteristics of these children led us to conduct a case note-based
      investigation of children admitted to 6 university hospitals with 2009 H1N1
      influenza. A total of 804 children was enrolled. The median age was 5 yr; 63.8%
      were males; and 22.4% had at least one chronic underlying disease. Ninety-five of
      the patients (11.8%) were critically ill and they suffered more from shortness of
      breath, dyspnea and lymphopenia than the other patients. Among all the patients,
      98.8% were treated with antivirals and 73% received treatment within 48 hr of
      illness onset. All the enrolled patients are alive and appear to have had good
      outcomes, probably due to the early intervention and antiviral treatment. This
      study deals with hospitalized children whose diagnoses of influenza A (H1N1) were
      confirmed, and therefore provides important new information about the clinical
      patterns of children with influenza A (H1N1) in Korea.

PMID- 22468106
TI  - Comparison of costs of endovascular repair versus open surgical repair for
      abdominal aortic aneurysm in Korea.
AB  - This study was designed to compare the hospital-related costs of elective
      abdominal aortic aneurysm (AAA) treatment and cost structure between endovascular
      aneurysm repair (EVAR) and open surgical repair (OSR) in Korean health care
      system. One hundred five primary elective AAA repairs (79 OSRs and 26 EVARs)
      performed in the Seoul National University Hospital from 2005 to 2009 were
      included. Patient characteristics were similar between two groups except for
      older age (P = 0.004) and more frequent history of malignancy (P = 0.031) in EVAR
      group. Thirty-day mortality rate was similar between two groups and there was no
      AAA-related mortality in both groups for 5 yr after repair. The total in-hospital
      costs for the index admission were significantly higher in EVAR patients (mean,
      KRW19,857,119) than OSR patients (mean KRW12,395,507) (P < 0.001). The
      reimbursement was also significantly higher in EVAR patients than OSR patients
      (mean, KRW14,071,081 vs KRW6,238,895, P < 0.001) while patients payments was
      comparable between two groups. EVAR patients showed higher follow-up cost up to 2
      yr due to more frequent imaging studies and reinterventions for type II endoleaks
      (15.4%). In the perspective of cost-effectiveness, this study suggests that the
      determination of which method to be used in AAA treatment be more finely trimmed
      and be individualized.

PMID- 22468107
TI  - Heterogeneous characteristics of Korean patients with dysferlinopathy.
AB  - Dysferlinopathy is caused by mutations in the DYSF gene. To characterize the
      clinical spectrum, we investigated the characteristics of 31 Korean
      dysferlinopathy patients confirmed by immunohistochemistry. The mean age of
      symptom onset was 22.23 +/- 7.34 yr. The serum creatine kinase (CK) was highly
      increased (4- to 101-fold above normal). The pathological findings of muscle
      specimens showed nonspecific dystrophic features and frequent inflammatory cell
      infiltration. Muscle imaging studies showed fatty atrophic changes dominantly in
      the posterolateral muscles of the lower limb. The patients with dysferlinopathy
      were classified by initial muscle weakness: fifteen patients with Miyoshi
      myopathy phenotype (MM), thirteen patients with limb girdle muscular dystrophy 2B
      phenotype (LGMD2B), two patients with proximodistal phenotype, and one
      asymptomatic patient. There were no differences between LGMD2B and MM groups in
      terms of onset age, serum CK levels and pathological findings. Dysferlinopathy
      patients usually have young adult onset and high serum CK levels. However,
      heterogeneity of clinical presentations and pathologic findings upon routine
      staining makes it difficult to diagnose dysferlinopathy. These limitations make
      immunohistochemistry currently the most important method for the diagnosis of
      dysferlinopathy.

PMID- 22468108
TI  - Interaction of morphine and selective serotonin receptor inhibitors in rats
      experiencing inflammatory pain.
AB  - Citalopram and paroxetine are selective serotonin reuptake inhibitors and also
      have antinociceptive effects. We investigated the antiallodynic and
      antihyperalgesic effects of intrathecally administered morphine, citalopram,
      paroxetine, and combinations thereof, in a rat model in which peripheral
      inflammation was induced by complete Freund's adjuvant (CFA). Drugs were
      intrathecally administered via direct lumbar puncture. Mechanical allodynia was
      measured using a Dynamic Plantar Aesthesiometer. Thermal hyperalgesia and cold
      allodynia were determined by measuring latency of paw withdrawal in response to
      radiant heat and cold water. Behavioral tests were run before and 15, 30, 45, and
      60 min after intrathecal injection. Intraplantar injection of CFA produced
      mechanical allodynia, thermal hyperalgesia, and cold allodynia. Intrathecally
      administered morphine (0.3 or 1 ug) had antiallodynic or antihyperalgesic effects
      (24.0%-71.9% elevation). The effects of morphine were significantly increased
      when a combination of citalopram (100 ug) and paroxetine (100 ug) was added
      (35.2%-95.1% elevation). This rise was reversed by naloxone and methysergide. The
      effects of citalopram and paroxetine were also reversed by naloxone and
      methysergide. We suggest that the mu opioid receptor and serotonin receptors play
      major roles in production of the antiallodynic and antihyperalgesic effects of
      morphine, citalopram, paroxetine, and combinations thereof, in animals
      experiencing inflammatory pain.

PMID- 22468109
TI  - Epidemiology of traumatic head injury in Korean children.
AB  - The aim of this study was to elucidate the epidemiology of traumatic head injury
      (THI) among Korean children. A prospective, in-depth trauma survey was conducted
      in five teaching hospitals. Data from all of the children who attended the
      emergency department (ED) were analyzed. From June 2008 to May 2009, 2,856
      children with THI visited the 5 EDs. The average age of the subjects was 5.6 (SD
      +/- 4.9) yr old, and 1,585 (55.5%) were 0-4 yr old. The male-to-female ratio was
      2.3 to 1 (1,979 vs 877). Consciousness levels of the subjects were classified
      according to the Glasgow Coma Scale (GCS), and 99.1%, 0.6%, and 0.4% were
      determined as mild, moderate, or severe injury, respectively, according to the
      GCS categorization. Most injuries occurred at home (51.3%), and the most common
      mechanism of injury was collision (43.2%). With regard to outcome, 2,682 (93.9%)
      patients were sent home, and 35 (1.2%) were transferred to another hospital. A
      total of 133 (4.7%) patients were hospitalized, and 38 (1.3%) underwent surgery.
      The incidence and characteristics of pediatric THI in Korea are affected by sex,
      location and injury mechanism.

PMID- 22468110
TI  - Late simultaneous presentation of left ventricular pseudoaneurysm and tricuspid
      regurgitation after blunt chest trauma.
AB  - A 32-yr-old man developed progressive exertional dyspnea 4 yr after blunt chest
      trauma due to an automobile accident. Two-dimensional echocardiography and
      computed-tomographic coronary angiography demonstrated a large pseudoaneurysm of
      the left ventricle and severe tricuspid regurgitation. The patient underwent
      successful surgical exclusion of the pseudoaneurysm by endoaneurysmal patch
      closure and repair of the tricuspid valve regurgitation. To the best of our
      knowledge, this is the first case of these 2 different pathologies presenting
      late simultaneously after blunt chest trauma and successful surgical repairs in
      the published literature.

PMID- 22468111
TI  - Immunoglobulin A nephropathy associated with Plasmodium falciparum malaria.
AB  - Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium
      falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA
      nephropathy for the first time. A 49-yr old male who had been to East Africa was
      diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria
      along with acute kidney injury developed during the course of the disease. Kidney
      biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial
      inflammation. Laboratory tests after recovery from malaria showed disappearance
      of urinary abnormalities and normalization of kidney function. Our findings
      suggest that malaria infection might be associated with IgA nephropathy.

PMID- 22468112
TI  - Temozolomide-associated bronchiolitis obliterans organizing pneumonia
      successfully treated with high-dose corticosteroid.
AB  - Temozolomide is an oral alkylating agent with clinical activity against
      glioblastoma multiforme (GM). It is generally well-tolerated and has few
      pulmonary side effects. We report a case of temozolomide-associated brochiolitis
      obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid
      treatment. A 56-yr-old woman presented with a 2-week history of exertional
      dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone
      surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy
      with temozolomide. After the 1st cycle, progressive dyspnea was gradually
      developed. Chest radiograph showed diffuse patchy peribronchovascular ground
      glass opacities in both lungs. Conventional dose of methylprednisolone (1
      mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung
      biopsy findings were compatible with BOOP, the patient's clinical course was more
      aggravated until hospital day 5. After the dose of methylprednisolone was
      increased (500 mg/day for 5 days) radiologic findings were improved dramatically.

PMID- 22468113
TI  - A case of spitzoid melanoma with lymph node metastasis in a child.
AB  - The distinction of a spitz nevus from a melanoma can be difficult and in some
      cases, impossible. A misdiagnosed spitz nevus can metastasize and lead to fatal
      outcomes, especially in children. A 5-yr-old girl presented with a 1-yr history
      of a solitary pinkish nodule on her left hand. On physical examination, she had a
      palpable left axillary lymph node. We performed biopsy and checked 3 sentinel
      lymph nodes (SLN) on her axillary area. The biopsy specimen showed multiple
      variably sized and shaped nests with large spindle or polygonal cells and SLN
      biopsy showed 3 of 3 lymph nodes that were metastasized. Under the diagnosis of
      spitzoid melanoma, she was treated with excision biopsy and complete left
      axillary lymph nodes were dissected. She received interferon-alpha2b
      subcutaneously at a dose of 8 MIU per day, 3 times weekly for 12 months, and
      shows no recurrence.

PMID- 22468114
TI  - Reversible dysphasia and statins.
AB  - This paper presents a case of reversible dysphasia occurring in a patient
      prescribed atorvastatin in combination with indapamide. A milder dysphasia
      recurred with the prescription of rosuvastatin and was documented on clinical
      examination. This resolved following cessation of rosuvastatin. The case
      highlights both a need for a wider understanding of potential drug interactions
      through the CYP 450 system and for an increased awareness, questioning and
      reporting of drug side-effects.

PMID- 22468115
TI  - Developmental Pathways in Juvenile Externalizing and Internalizing Problems.

PMID- 22468116
TI  - Parental Religious Socialization Practices, Connectedness With Others, and
      Depressive Symptoms in Late Life.
AB  - This purpose of this study is to examine two constructs that have been largely
      overlooked in the study of religious involvement among older people: parental
      religious socialization practices and feelings of connectedness with others. The
      data are from an ongoing nationwide survey of older people. Findings from a
      latent variable model that was designed to examine the two focal constructs
      provides support for the following relationships:(1) older people whose parents
      encouraged them to become more involved in religion are more likely to attend
      worship services; (2) older people whose parents promoted religious involvement
      and older individuals who attend church more often are more likely to report that
      they see a fundamental connection among all human beings; (3) older adults who
      feel more closely connected to others will be more likely to forgive people for
      the things they have done; and (4) older people who are more forgiving are likely
      to experience fewer symptoms of depression over time.

PMID- 22468117
TI  - The Impact of Social Support on the Relationship between Trauma History and PTSD
      Symptoms in Motor Vehicle Accident Victims.
AB  - The present study examined how different types of social support differentially
      moderated the relationship between trauma history characteristics and the
      development of posttraumatic stress disorder symptoms (PTSS) following a motor
      vehicle accident (MVA). Two hundred thirty-five MVA victims self-reported levels
      of social support and trauma history, and were evaluated for PTSS 6- and 12
      months post-MVA. Results indicated that after controlling for gender, injury
      severity and income, number of prior trauma types and subjective responses to
      prior traumatization predicted subsequent PTSS (ps < .05). Appraisal social
      support was a significant moderator of the total number of types of trauma
      (appraisal: 6-months beta = -.16, p < .05; 12-months beta = -.17, p < .05) and
      subjective physical injury during the prior trauma (appraisal: 6-months beta = 
      .14, p < .05; 12-months beta = -.19, p < .05) in predicting PTSS. Results
      underscore the importance of examining both trauma history and social support as
      multi-dimensional constructs and suggest merit to addressing social support in
      trauma victims with a prior trauma history.

PMID- 22468118
TI  - Attachment Behavior of Children Adopted Internationally at Six Months Post
      Adoption.
AB  - The purpose of this pilot study was to describe attachment behavior in children
      adopted internationally at 6 months post adoption. Twenty-two children and their
      adoptive mothers were observed at home for completion of an attachment measure.
      Mothers also completed a questionnaire on their child's preadoption care.
      Comparisons of children low and high in attachment security suggested that low
      secure children showed predominantly ambivalent attachment behavior or that they
      were still in the process of forming an attachment. Children having foster versus
      orphanage care prior to adoption differed in quality of preadoption care and in
      certain attachment behaviors, but not in overall attachment security.

PMID- 22468120
TI  - Dr Noni MacDonald Award.

PMID- 22468119
TI  - The Canadian Paediatric Surveillance Program: Celebrating 15 years of successful
      paediatric surveillance.

PMID- 22468121
TI  - Case 1: Going forward in lack of movement.

PMID- 22468122
TI  - Case 2: Where did you get that DRESS?

PMID- 22468123
TI  - Use of array genomic hybridization technology for constitutional genetic
      diagnosis in Canada.

PMID- 22468124
TI  - Health care professionals' grief after the death of a child.
AB  - OBJECTIVES: To evaluate the intensity of grief experienced by health care
      professionals (HPs) after the death of a child, to explore factors associated
      with a memorable death (defined as an unforgettable child's death that has
      touched them in their career) and to identify the needs of HPs. METHODS: A cross
      sectional study was performed to assess emotional reactions, coping strategies
      and perceived needs of paediatric HPs in a general hospital. RESULTS: One hundred
      one HPs (46 nurses, 22 paediatric physicians, 11 paediatric residents, 13
      respiratory therapists and nine 'others') completed the questionnaire. The level
      of grief experienced by HPs after a memorable death was intense. Respiratory
      therapists showed the highest mean (+/- SD) intensity of grief after a memorable
      death versus other HPs, as measured by the Texas Revised Inventory of Grief
      (TRIG) (29+/-15 versus 16+/-14; P=0.002). Younger HPs (20 to 25 years of age)
      reported higher early grief intensity than older ones (older than 50 years of
      age) (22+/-16 versus 10+/-8; P=0.01). There was no significant association
      between the TRIG score and an HP being a parent, having received palliative care
      training or the length of his/her relationship with the child and family. Seventy
      per cent of HPs spoke with their colleagues after the death of a child and 48%
      with family and friends. Many participants (37%) believed that this social
      support helped them the most. CONCLUSION: Grief after a child's death is intense
      for HPs. This emotional intensity and difference between professions raises
      issues about the emotional support received following the death of a patient.

PMID- 22468126
TI  - Ankyloglossia and breastfeeding.
AB  - Ankyloglossia (or tongue-tie) is a relatively uncommon congenital anomaly defined
      by an abnormally short lingual frenulum. Associations between tongue-tie and
      breastfeeding problems in infants have been inconsistent, and are a longstanding
      source of controversy in the medical community. Definitions of ankyloglossia
      vary, and management suggestions are not based on randomized controlled trials.
      Surgical correction involves cutting the lingual frenulum (frenotomy). Based on
      current available evidence, frenotomy cannot be recommended. If, however, the
      association between significant tongue-tie and major breastfeeding problems is
      clearly identified and surgical intervention is deemed necessary, frenotomy
      should be performed by a clinician experienced with the procedure and with
      appropriate analgesia. More definitive recommendations regarding the management
      of tongue-tie in infants await appropriately designed trials.

PMID- 22468125
TI  - Trends in paediatric sport- and recreation-related injuries: An injury
      surveillance study at the British Columbia Children's Hospital (Vancouver,
      British Columbia) from 1992 to 2005.
AB  - BACKGROUND: Sport- and recreation-related injuries are a major source of
      morbidity in the paediatric population. Long-term trends for these injuries are
      largely unknown. METHODS: A traumatic injury surveillance system (the Canadian
      Hospitals Injury Reporting and Prevention Program) was used to examine the
      demographics and trends of paediatric sports injuries in children who presented
      to or were directly admitted to the British Columbia Children's Hospital
      (Vancouver, British Columbia) emergency department or intensive care unit from
      1992 to 2005. RESULTS: Over the 14-year study period, there was a significant
      increase in sport- and recreation-related injuries among patients who presented
      to the British Columbia Children's Hospital. Of 104,414 injuries between 1992 and
      2005, 27,466 were related to sports and recreational activities. The number of
      sport-related injuries increased by 28%, while all-cause injuries did not change
      significantly. Males comprised 68% of the sport-related injuries, and both sexes
      displayed an increasing trend over time. Cycling, basketball, soccer and ice
      hockey were the top four injury-causing activities. The main body parts injured
      were the face, head and digits. CONCLUSIONS: Paediatric sports injuries
      significantly increased at the British Columbia Children's Hospital over the 14
      year study period. This is likely due to increased sport participation, increased
      risk associated with certain sports, or both. Trends in paediatric sports injury
      may be predicted by changes in popular media, possibly allowing prevention
      programs to help to avoid these injuries before they occur.

PMID- 22468127
TI  - Ethical participation of children and youth in medical education.
AB  - Children and youth (referred to as 'children' in the present statement), whether
      actual patients or volunteers, frequently participate in medical education. The
      present position statement discusses the numerous ethical challenges that may
      arise including respect for persons, truth telling and confidentiality. The
      statement provides guidelines that may be helpful to educators from a wide
      variety of disciplines.

PMID- 22468128
TI  - Update on the success of the pneumococcal conjugate vaccine.
AB  - Several years after the seven-valent pneumococcal conjugate vaccine (PCV7) was
      introduced in Canada and elsewhere, routine infant vaccination has led to near
      eradication of invasive pneumococcal disease caused by vaccine serotype strains
      in both children and adults. There have also been significant declines in
      pneumococcal-related disease including lobar pneumonia and otitis media. These
      declines have been offset, to some extent, by increases in nonvaccine serotype
      disease. Serotype 19A, which is often highly resistant to antibiotics, has become
      predominant. In most populations, however, the magnitude of replacement disease
      is much lower than the magnitude of decline in invasive pneumococcal disease with
      the use of PCV7. There is increasing evidence that three PCV7 doses provide
      protection that is nearly identical to that of four doses. New 10-valent and 13
      valent pneumococcal conjugate vaccines were recently approved in Canada. These
      vaccines increase pneumococcal serotype coverage including serotype 19A (present
      in the 13-valent vaccine). Many provinces and territories have incorporated the
      13-valent vaccine in their vaccination programs.

PMID- 22468129
TI  - Withholding and withdrawing artificial nutrition and hydration.
AB  - Although the practice of withholding and withdrawing artificial nutrition and
      hydration (ANH) has become more common, it remains controversial, particularly in
      the paediatric setting. Decisions regarding ANH, along with other medical
      interventions, should be considered in the individual context of the child's
      overall plan of care. The purpose of the present practice point is to provide
      guidance for Canadian paediatric health care practitioners regarding when
      withholding or withdrawing ANH may be an ethically permissible option as part of
      a palliative care plan and to briefly address some pragmatic considerations.

PMID- 22468130
TI  - Letter to the editor.

PMID- 22468131
TI  - Pregnancy and contraception in young women with congenital heart disease: General
      considerations.
AB  - Young women with heart disease are increasingly being seen in obstetrical
      referral centres owing, in large part, to the dramatic improvements in survival
      of young adults with congenital heart disease in recent years. Although
      pregnancies in most women with heart disease result in favourable outcomes, there
      are important exceptions that must be recognized. These exceptions pose
      significant mortality risk to the mother and/or the fetus. The present article
      outlines cardiovascular adaptations to pregnancy, general outcomes and management
      considerations for practitioners caring for pregnant young women with congenital
      heart disease. A lesion-specific review is published in a complementary article.

PMID- 22468132
TI  - Variation in captopril formulations in pharmacies across Canada.
AB  - Captopril, an angiotensin-converting enzyme inhibitor used to manage congestive
      heart failure in the paediatric population, has limited data on efficacy and
      safety. Its variety of liquid formulations dispensed by different pharmacies
      poses a challenge in optimizing captopril dosing in patients. Fourteen tertiary
      paediatric centre pharmacies across Canada were contacted to decipher the type of
      captopril formulation they dispense, their recipe and the stability of each
      formulation. Of the 14 centres surveyed, four dispensed solid tablets, two
      dispensed either solid tablets or liquid formulations, and eight dispensed
      extemporaneously prepared liquid formulations. There was also great variety in
      the solutions used to prepare the liquid formulations. The bioequivalence of
      these preparations has not been studied. As a result, physicians cannot be
      certain about the effective dose of captopril. Uniformity is recommended among
      paediatric pharmacies in Canada when preparing medications such as captopril.
      Proper testing of the stability and bioequivalence of medications is recommended.

PMID- 22468133
TI  - Linguistic and metalinguistic outcomes of intense immersion education: How
      bilingual?
AB  - Anglophone children in Grades 2 and 5 who attended an intensive French immersion
      program were examined for linguistic and metalinguistic ability in English and
      French. Measures of linguistic proficiency (vocabulary and grammatical knowledge)
      were consistently higher in English and remained so even after five years of
      immersion education in French. Measures of metalinguistic ability (letter fluency
      and ignoring semantic anomalies in sentence judgments) in French improved
      significantly over the two grades studied and closed the gap (letter fluency) or
      caught up with (sentence judgments) similar performance in English. This
      dissociation between developmental trajectories for linguistic and metalinguistic
      development is exactly the pattern expected for fully bilingual children,
      endorsing immersion education as a route to bilingualism.

PMID- 22468134
TI  - Regulation of polyisoprenylated methylated protein methyl esterase by
      polyunsaturated fatty acids and prostaglandins.
AB  - Polyisoprenylation is a set of secondary modifications involving proteins whose
      aberrant activities are implicated in cancers and degenerative disorders. The
      last step of the pathway involves an ester-forming polyisoprenylated protein
      methyl transferase- and hydrolytic polyisoprenylated methylated protein methyl
      esterase (PMPMEase)-catalyzed reactions. Omega-3 and omega-6 polyunsaturated
      fatty acids (PUFAs) have been linked with antitumorigeneis and tumorigenesis,
      respectively. PUFAs are structurally similar to the polyisoprenyl groups and may
      interfere with polyisoprenylated protein metabolism. It was hypothesized that
      PUFAs may be more potent inhibitors of PMPMEase than their more polar oxidative
      metabolites, the prostaglandins. As such, the relative effects of PUFAs and
      prostaglandins on PMPMEase could explain the association between cyclooxygenase-2
      (COX-2) expression in tumors, the chemopreventive effects of the non-steroidal
      anti-inflammatory (NSAIDs) COX-2 inhibitors and PUFAs. PUFAs such as arachidonic
      (AA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids inhibited PMPMEase
      activity with Ki values of 0.12 to 3.7 MUM. The most potent prostaglandin was 63
      fold less potent than AA. The PUFAs were also more effective at inducing
      neuroblastoma cell death at physiologically equivalent concentrations. The lost
      PMPMEase activity in AA-treated degenerating cells was restored by incubating the
      lysates with COX-1 or COX-2. PUFAs may thus be physiological regulators of cell
      growth and could owe these effects to PMPMEase inhibition.

PMID- 22468135
TI  - TOUCH-UP gradient amplification method.
AB  - We report a unique amplification technique that works efficiently and
      specifically over a temperature range, rather than at one specific temperature,
      throughout the amplification process. As bisulfite-modified DNA is one of the
      difficult to amplify templates, we used this technique to amplify regions of
      promoter-associated CpG island for 11 genes using this template. This technique
      amplified specific products for every gene without requiring any optimization.

PMID- 22468136
TI  - Random amplification and pyrosequencing for identification of novel viral genome
      sequences.
AB  - ssRNA viruses have high levels of genomic divergence, which can lead to
      difficulty in genomic characterization of new viruses using traditional PCR
      amplification and sequencing methods. In this study, random reverse
      transcription, anchored random PCR amplification, and high-throughput
      pyrosequencing were used to identify orthobunyavirus sequences from total RNA
      extracted from viral cultures of acute febrile illness specimens. Draft genome
      sequence for the orthobunyavirus L segment was assembled and sequentially
      extended using de novo assembly contigs from pyrosequencing reads and
      orthobunyavirus sequences in GenBank as guidance. Accuracy and continuous
      coverage were achieved by mapping all reads to the L segment draft sequence.
      Subsequently, RT-PCR and Sanger sequencing were used to complete the genome
      sequence. The complete L segment was found to be 6936 bases in length, encoding a
      2248-aa putative RNA polymerase. The identified L segment was distinct from
      previously published South American orthobunyaviruses, sharing 63% and 54%
      identity at the nucleotide and amino acid level, respectively, with the complete
      Oropouche virus L segment and 73% and 81% identity at the nucleotide and amino
      acid level, respectively, with a partial Caraparu virus L segment. The result
      demonstrated the effectiveness of a sequence-independent amplification and next
      generation sequencing approach for obtaining complete viral genomes from total
      nucleic acid extracts and its use in pathogen discovery.

PMID- 22468137
TI  - Isobaric labeling and data normalization without requiring protein quantitation.
AB  - Isobaric multiplexed quantitative proteomics can complement high-resolution
      sample isolation techniques. Here, we report a simple workflow exponentially
      modified protein abundance index (emPAI)-MW deconvolution (EMMOL) for normalizing
      isobaric reporter ratios within and between experiments, where small or unknown
      amounts of protein are used. EMMOL deconvolutes the isobaric tags for relative
      and absolute quantification (iTRAQ) data to yield the quantity of each protein of
      each sample in the pool, a new approach that enables the comparison of many
      samples without including a channel of reference standard. Moreover, EMMOL allows
      using a sufficient quantity of control sample to facilitate the peptide
      fractionation (isoelectric-focusing was used in this report), and mass
      spectrometry MS/MS sequencing yet relies on the broad dynamic range of iTRAQ
      quantitation to compare relative protein abundance. We demonstrated EMMOL by
      comparing four pooled samples with 20-fold range differences in protein abundance
      and performed data normalization without using prior knowledge of the amounts of
      proteins in each sample, simulating an iTRAQ experiment without protein
      quantitation prior to labeling. We used emPAI, the target protein MW, and the
      iTRAQ reporter ratios to calculate the amount of each protein in each of the four
      channels. Importantly, the EMMOL-delineated proteomes from separate iTRAQ
      experiments can be assorted for comparison without using a reference sample. We
      observed no compression of expression in iTRAQ ratios over a 20-fold range for
      all protein abundances. To complement this ability to analyze minute samples, we
      report an optimized iTRAQ labeling protocol for using 5 MUg protein as the
      starting material.

PMID- 22468138
TI  - Rapid detection of the ACMG/ACOG-recommended 23 CFTR disease-causing mutations
      using ion torrent semiconductor sequencing.
AB  - Cystic fibrosis (CF) is one of the most frequently diagnosed autosomal-recessive
      diseases in the Caucasian population. For general-population CF carrier
      screening, the American College of Medical Genetics (ACMG)/American College of
      Obstetricians and Gynecologists (ACOG) have recommended a core panel of 23
      mutations that will identify 49-98% of carriers, depending on ethnic background.
      Using a genotyping technology that can rapidly identify disease-causing mutations
      is important for high-throughput general-population carrier screening, confirming
      clinical diagnosis, determining treatment options, and prenatal diagnosis. Here,
      we describe a proof-of-concept study to determine whether the Ion Torrent
      Personal Genome Machine (PGM) sequencer platform can reliably identify all
      ACMG/ACOG 23 CF transmembrane conductance regulator (CFTR) mutations. A WT CF
      specimen along with mutant DNA specimens representing all 23 CFTR mutations were
      sequenced bidirectionally on the Ion Torrent 314 chip to determine the accuracy
      of the PGM for CFTR variant detection. We were able to reliably identify all of
      the targeted mutations except for 2184delA, which lies in a difficult, 7-mer
      homopolymer tract. Based on our study, we believe PGM sequencing may be a
      suitable technology for identifying CFTR mutations in the future. However, as a
      result of the elevated rate of base-calling errors within homopolymer stretches,
      mutations within such regions currently need to be evaluated carefully using an
      alternative method.

PMID- 22468140
TI  - Direct and indirect effects in a logit model.
AB  - This article discusses a method by Erikson et al. (2005) for decomposing a total
      effect in a logit model into direct and indirect effects. Moreover, this article
      extends this method in three ways. First, in the original method the variable
      through which the indirect effect occurs is assumed to be normally distributed.
      In this article the method is generalized by allowing this variable to have any
      distribution. Second, the original method did not provide standard errors for the
      estimates. In this article the bootstrap is proposed as a method of providing
      those. Third, I show how to include control variables in this decomposition,
      which was not allowed in the original method. The original method and these
      extensions are implemented in the ldecomp package.

PMID- 22468141
TI  - From Bio 101 to Pillars of Biology: A Pedagogical Experiment.

PMID- 22468142
TI  - Retention of total carotenoid and beta-carotene in yellow sweet cassava (Manihot
      esculenta Crantz) after domestic cooking.
AB  - BACKGROUND: Over the last decade, considerable efforts have been made to identify
      cassava cultivars to improve the vitamin A nutritional status of undernourished
      populations, especially in northeast Brazil, where cassava is one of the
      principal and essentially only nutritional source. OBJECTIVES: The aim of this
      study was to evaluate the total carotenoid, beta-carotene, and its all-E-, 9-,
      and 13-Z-beta-carotene isomers content in seven yellow sweet cassava roots and
      their retention after three boiling cooking methods. DESIGN: The total
      carotenoid, beta-carotene, and its all-E-, 9-, and 13-Z-beta-carotene isomers in
      yellow sweet cassava samples were determined by ultraviolet/visible spectrometry
      and high-performance liquid chromatography, respectively, before and after
      applying the cooking methods. All analyses were performed in triplicate. RESULTS:
      The total carotenoid in raw roots varied from 2.64 to 14.15 ug/g and total beta
      carotene from 1.99 to 10.32 ug/g. The beta-carotene predominated in all the
      roots. The Hibrido 2003 14 08 cultivar presented the highest beta-carotene
      content after cooking methods 1 and 3. The 1153 - Klainasik cultivar presented
      the highest 9-Z-beta-carotene content after cooking by method 3. The highest
      total carotenoid retention was observed in cultivar 1456 - Vermelhinha and that
      of beta-carotene for the Hibrido 2003 14 11 cultivar, both after cooking method
      1. Evaluating the real retention percentage (RR%) in sweet yellow cassava after
      home cooking methods showed differences that can be attributed to the total
      initial carotenoid contents. However, no cooking method uniformly provided a
      higher total carotenoid or beta-carotene retention in all the cultivars.
      CONCLUSION: Differences were found in the cooking methods among the samples
      regarding total carotenoid or beta-carotene retention, suggesting that the
      different behaviors of the cultivars need to be further analyzed. However, high
      percentages of total carotenoid or beta-carotene retention were observed and can
      minimize vitamin A deficiency in low-income populations.

PMID- 22468143
TI  - A reversal of decreasing trends in population cholesterol levels in Vasterbotten
      County, Sweden.
AB  - BACKGROUND: High cholesterol is identified as a major risk factor for chronic non
      communicable diseases, especially cardiovascular and cerebrovascular diseases.
      Monitoring trends of cholesterol levels and comparing trends across population
      groups are important to assess population distribution and risks related to
      cholesterol change over time. Cholesterol surveillance data are lacking, even in
      high-income countries. OBJECTIVES: To describe the trends in cholesterol and
      triglyceride levels in different population groups and to estimate the risk of
      developing hypercholesterolemia and hypertriglyceridemia in Vasterbotten County,
      Sweden during 1990-2010. DESIGNS AND METHODS: Since 1990, 133,082 individuals
      living in Vasterbotten County, Northern Sweden, invited on their 30th, 40th, 50th
      and 60th birthdays, participated in the Vasterbotten Intervention Program. Ten
      years after baseline data collection, 34,868 individuals were surveyed for a
      second time. In addition to a self-administered health questionnaire (that
      included information on socioeconomic status, demographics, self-reported health
      and lifestyle behaviours), blood cholesterol and triglyceride were examined.
      RESULTS: The level and prevalence of hypercholesterolemia decreased significantly
      from 1990 to 2007, but the trends began to increase during 2008-2010 in men,
      women, and in all educational groups. Men had significantly higher serum
      triglyceride levels than women and their cholesterol levels were similar to those
      of the women. This study shows that those with basic education and who live in
      rural inlands had consistently higher triglyceride level than those who live in
      the city and have higher educational attainments. People with basic education are
      also at higher risk of developing hypercholesterolemia and hypertriglyceridemia
      at 10-year follow-up; the risk is much higher among the older cohorts,
      particularly women. During 1990-2010, the proportion of participants who reported
      treatment with lipid-lowering agents increased from 1.1% to 9.6% among men and
      0.5% to 5.3% among women. About 60% of those treated achieved treatment goals for
      cholesterol or triglycerides. CONCLUSIONS: The increasing trend in cholesterol
      level in the Vasterbotten population during 2008-2010 needs to be closely
      monitored. Addressing the unequal distribution of cholesterol, as well as other
      risk factors such as obesity, physical inactivity, high blood glucose, among
      those with basic education, and particularly among populations in rural areas are
      important to prevent higher burdens of chronic non-communicable diseases in this
      population.

PMID- 22468144
TI  - The influences of reproductive status and acute stress on the levels of
      phosphorylated mu opioid receptor immunoreactivity in rat hippocampus.
AB  - Opioids play a critical role in hippocampally dependent behavior and plasticity.
      In the hippocampal formation, mu opioid receptors (MOR) are prominent in
      parvalbumin (PARV) containing interneurons. Previously we found that gonadal
      hormones modulate the trafficking of MORs in PARV interneurons. Although sex
      differences in response to stress are well documented, the point at which
      opioids, sex and stress interact to influence hippocampal function remains
      elusive. Thus, we used quantitative immunocytochemistry in combination with light
      and electron microscopy for the phosphorylated MOR at the SER375 carboxy-terminal
      residue (pMOR) in male and female rats to assess these interactions. In both
      sexes, pMOR-immunoreactivity (ir) was prominent in axons and terminals and in a
      few neuronal somata and dendrites, some of which contained PARV in the mossy
      fiber pathway region of the dentate gyrus (DG) hilus and CA3 stratum lucidum. In
      unstressed rats, the levels of pMOR-ir in the DG or CA3 were not affected by sex
      or estrous cycle stage. However, immediately following 30 minutes of acute
      immobilization stress (AIS), males had higher levels of pMOR-ir whereas females
      at proestrus and estrus (high estrogen stages) had lower levels of pMOR-ir within
      the DG. In contrast, the number and types of neuronal profiles with pMOR-ir were
      not altered by AIS in either males or proestrus females. These data demonstrate
      that although gonadal steroids do not affect pMOR levels at resting conditions,
      they are differentially activated both pre- and post-synaptic MORs following
      stress. These interactions may contribute to the reported sex differences in
      hippocampally dependent behaviors in stressed animals.

PMID- 22468145
TI  - Disclosure of HIV Diagnosis to HIV-Infected Children in South Africa: Focus
      Groups for Intervention Development.
AB  - Worldwide about 2.5 million children younger than 15 years of age are living with
      HIV, and more than 2.3 million of them live in sub-Saharan Africa. Antiretroviral
      therapy has reduced mortality among HIV-infected children, and as they survive
      into adolescence, disclosing to them their diagnosis has emerged as a difficult
      issue, with many adolescents unaware of their diagnosis. There is a need to build
      an empirical foundation for strategies to appropriately inform infected children
      of their diagnosis, particularly in South Africa, which has the largest number of
      HIV-positive people in the world. As a step toward developing such strategies, we
      conducted a study in Eastern Cape Province, South Africa to identify beliefs
      about disclosing HIV diagnosis to HIV-infected children among caregivers, health
      care providers, and HIV-positive children who knew their diagnosis. We
      implemented 7 focus groups with 80 participants: 51 caregivers in 4 groups, 24
      health-care providers in 2 groups, and 5 HIV-positive children in 1 group. We
      found that although the participants believed that children from age 5 years
      should begin to learn about their illness, with full disclosure by age 12, they
      suggested that many caregivers fail to fully inform their children. The
      participants said that the primary caregiver was the best person to disclose. The
      main reasons cited for failing to disclose were (a) lack of knowledge about HIV
      and its treatment, (b) the concern that the children might react negatively, and
      (c) the fear that the children might inappropriately disclose to others, which
      would occasion gossip, stigmatization, and discrimination towards them and the
      family. We discuss the implications for developing interventions to help
      caregivers appropriately disclose HIV status to HIV-infected children and, more
      generally, communicate effectively with the children to improve their health
      outcomes.

PMID- 22468147
TI  - Experiences of being exposed to intimate partner violence during pregnancy.
AB  - In this study a phenomenological approach was used in order to enter deeply into
      the experience of living with violence during pregnancy. The aim of the study was
      to gain a deeper understanding of women's experiences of being exposed to
      intimate partner violence (IPV) during pregnancy. The data were collected through
      in-depth interviews with five Norwegian women; two during pregnancy and three
      after the birth. The women were between the age of 20 and 38 years. All women had
      received support from a professional research and treatment centre. The essential
      structure shows that IPV during pregnancy is characterized by difficult
      existential choices related to ambivalence. Existential choices mean questioning
      one's existence, the meaning of life as well as one's responsibility for oneself
      and others. Five constituents further explain the essential structure: Living in
      unpredictability, the violence is living in the body, losing oneself, feeling
      lonely and being pregnant leads to change. Future life with the child is
      experienced as a possibility for existential change. It is important for health
      professionals to recognize and support pregnant women who are exposed to violence
      as well as treating their bodies with care and respect.

PMID- 22468148
TI  - Multianalyte assay systems in the differential diagnosis of ovarian cancer.
AB  - INTRODUCTION: The efficient triage of women diagnosed with a pelvic mass presents
      a current area of unmet need. Unnecessary surgical intervention performed on
      patients at a decreased risk of malignancy represents a significant source of
      preventable morbidity, anxiety and cost. Likewise, delayed or overlooked referral
      of patients harboring malignant tumors is strongly associated with diminished
      outcomes. Current tools including imaging modalities and the CA 125 blood test
      are of insufficient accuracy to overcome these challenges. The use of
      multianalyte assays systems which include additional biomarkers capable of
      complementing the performance of CA 125 may offer the best hope of improvement.
      AREAS COVERED: Recent findings regarding the use of multianalyte biomarker panels
      for the differential diagnosis of a pelvic mass are reviewed and discussed.
      Particular attention is paid to to the FDA approved ROMA and OVA1 tests. The
      development, validation, recent evaluation and comparative performances of these
      two tests are reviewed in detail. EXPERT OPINION: The performances achieved by
      the ROMA and OVA1 diagnostic tests represent significant milestones in the
      application of multianalyte assay systems into standard clinical practice. The
      overall impact and cost-effectiveness of widespread clinical use of these tools
      remains to be evaluated.

PMID- 22468149
TI  - Antinociceptive activity of Mentha piperita leaf aqueous extract in mice.
AB  - BACKGROUND: Mentha piperita L. (Labiatae) is an herbaceous plant, used in folk
      medicine for the treatment of several medical disorders. METHODS AND RESULTS: In
      the present study, the aqueous extract of Mentha piperita leaf, at the i.p doses
      200 and 400 mg/kg, showed significant analgesic effects against both acetic acid
      induced writhing and hot plate-induced thermal stimulation in mice, with
      protection values of 51.79% and 20.21% respectively. On the contrary, the Mentha
      piperita leaf aqueous extract did not exhibit anti-inflammatory activity against
      carrageenan induced paw oedema. CONCLUSION: These findings indicate that Mentha
      piperita has a potential analgesic effect that may possibly have mediated
      centrally and peripherally, as well as providing a pharmacological evidence for
      its traditional use as a pain reliever.

PMID- 22468150
TI  - Continued growth of the hip after fixation of slipped capital femoral epiphysis
      using a single cannulated screw with a proximal threading.
AB  - BACKGROUND: The most commonly used method for unstable slipped capital femoral
      epiphysis (SCFE) remains in situ fixation. Depending on the surgeon's preference,
      screws or Kirschner wires are used for stabilizing the slipped upper femoral
      epiphysis. The purpose of this study was to evaluate the ability of a single
      cannulated screw with a proximal threading to ensure stabilization, growth, and
      remodeling of the slipped epiphysis. METHODS: A retrospective study was performed
      identifying 23 children treated for unstable SCFE under 50 degrees  by means of a
      single cannulated screw with proximal threading. All patients attended a
      radiological evaluation immediately after surgery and at physeal closure. The
      width of the epiphysis cut by the Klein line, the width and length of the femoral
      neck, the centrocalcar distance (CCD) angle, and the articulotrochanteric
      distance (ATD) were evaluated. RESULTS: All patients had a stabilized epiphysis
      at the last follow-up, with no case of recurring slip. Radiological comparison of
      the affected side between the preoperative and the last follow-up evaluation
      showed a statistically significant improvement in the neck length and width.
      CONCLUSION: Fixation of the epiphysis using proximally threaded screws allows the
      preservation of femoral neck growth. The cannulated screw with proximal threading
      seems to be a safe and relevant implant to help to restore a close-to-normal hip
      at skeletal maturity.

PMID- 22468146
TI  - Initiation of lytic DNA replication in Epstein-Barr virus: search for a common
      family mechanism.
AB  - Herpesviruses are a complex family of dsDNA viruses that are a major cause of
      human disease. All family members share highly related viral replication
      proteins, such as DNA polymerase, ssDNA-binding proteins and processivity
      factors. Consequently, it is generally thought that lytic replication occurs
      through a common and conserved mechanism. However, considerable evidence
      indicates that proteins controlling initiation of DNA replication vary greatly
      among the herepesvirus subfamilies. In this article, we focus on some of the
      known mechanisms that regulate Epstein-Barr virus lytic-cycle replication, and
      compare this to other herpesvirus family members. Our reading of the literature
      leads us to conclude that diverse viral mechanisms generate a common
      nucleoprotein prereplication structure that can be recognized by a highly
      conserved family of viral replication enzymes.

PMID- 22468151
TI  - Treatment outcome in the most severely affected Legg-Perthes patients, comparing
      prolonged traction in abduction with femoral varus derotation treatment.
AB  - PURPOSE: Compare conservative and operative treatment in the most severely
      affected Legg-Perthes disease patients. METHODS: 29 patients (14 conservative and
      15 operative) with 32 affected hips (16 conservative and 16 operative) were
      evaluated, all Catterall 3 or 4. The conservative group, with a median age-at
      onset of 4.8 (range, 2.5-9.5) years, was treated by a rigorous regime of traction
      in abduction for an average of two years. Follow-up was performed at a median of
      28.6 (range, 17.4-31.6) years with a median patient age of 34.1 (range, 19.9
      39.3) years. The operative group, with a median age-at-onset of 4.7 (range, 2.0
      7.8) years, was treated by femoral varus derotation osteotomy. Follow-up was
      performed at a median of 14 (range, 8-21.4) years, with a median patient age of
      20.7 (range, 12.8-28) years. RESULTS: Median age-at-onset (P = 0.16) and
      Catterall classification (P = 0.29) were comparable. No differences could be
      found for the Stulberg classification (P = 0.83), functional parameters (Harris
      Hip score and Merle d'Aubigne and Postel), and leg-length differences. Career
      choices were similar for both patient groups, as well. CONCLUSIONS: Given
      methodological issues, femoral varus derotation osteotomy did not show apparent
      better results than the conservative containment regime in Catterall 3 and 4
      patients with a median age-at-onset around 4.8 years. This result is fairly
      similar to recent literature suggesting a conservative approach in most severely
      affected patients with a young age-at-onset. However, based on unacceptable
      socioeconomic issues, the conservative regime evaluated in the present study
      cannot be justified, nowadays.

PMID- 22468152
TI  - Are extremity musculoskeletal injuries in children related to obesity and social
      status? A prospective observational study in a district general hospital.
AB  - BACKGROUND: Obesity is one of the several independent risk factors for the risk
      of fractures. Major epidemiological studies also suggested the social status of
      the patients to be a confounding factor. We aimed to look at the influence of
      obesity on fractures and to determine if the social status of the patients is a
      confounding factor. METHODS: This is an observational study of 560 children with
      musculoskeletal injuries who presented over a period of 8 months and the data
      were collected prospectively. Obesity status and social deprivation index were
      estimated. RESULTS: The prevalence of overweight and obese children was 29.9%.
      Twenty-four percent of the boys and 31% of the girls were obese (P = 0.2). In the
      group of most deprived areas, the prevalence of obesity increased to 40% in those
      needing admission for intervention. CONCLUSIONS: Although there is a slight
      increase in obesity, there is no suggestion of increased rate of fractures in
      deprived areas. Upper limb injuries were more predominant, with distal radius
      fracture being the most common injury. Boys sustain fractures twice as often as
      girls. There is a tendency to increasing obesity with increasing age.

PMID- 22468153
TI  - Open fractures of the femur in children: analysis of various treatment methods.
AB  - PURPOSE: To describe the demographic and clinical characteristics of children who
      presented with open femur fractures. METHODS: A retrospective chart review of all
      children treated for open femur fractures at the McGill University Health Center
      between 1980 and 2009 was conducted. Thirty-seven patients (28 males and 9
      females) were identified. Union was determined clinically by the absence of pain,
      tenderness to palpation and crepitus with motion. Complications were reported.
      RESULTS: The mean age of the patients was 11.5 years (range 2.8-18.1 years). The
      mechanism of injury involved motor vehicle-related injuries in 70% of cases.
      There were 13 Grade I, 15 Grade II and 9 Grade III fractures. The treatment
      involved traction and hip spica in 11 patients, external fixator in nine
      patients, intramedullary nailing in seven patients, open reduction and internal
      fixation in six patients, and traction and an ischial weight bearing brace in
      four patients. Average time to union was 5.1 months (range 1.5-14.4 months).
      Infections occurred in ten patients, nine had delayed unions, two developed
      malunions, four had a refracture and four patients developed a limb length
      discrepancy >2 cm. CONCLUSIONS: Open fractures of the femur are often accompanied
      by associated injuries, indicating the importance of early and comprehensive
      treatment. Treatment may include hip spica application in school-age children and
      solid intramedullary nails in adolescents. In children with multiple injuries,
      specifically those with higher fracture grades, treatment with an external
      fixator provides immediate stability of the fracture and allows early
      mobilization and ease of management of associated injuries.

PMID- 22468154
TI  - The effect of posterior spinal releases on axial correction torque: a cadaver
      study.
AB  - PURPOSE: Posterior only approaches for spinal deformity are increasingly popular
      and posterior spinal release is utilized to gain flexibility for correctional
      maneuvers. Prior biomechanical data support the use of facetectomy and rib head
      resection for gaining flexibility in the sagittal and coronal planes but to date
      there has been no quantification of stiffness reduction provided by these
      techniques for axial correction through a pedicle screw construct. We sought to
      determine the contribution of posterior spinal releases (facetectomy, rib head
      resection) on axial plane stiffness. METHODS: Four fresh-frozen human cadavers
      were instrumented with fixed angle pedicle screws in the thoracic spine. The
      torque needed to produce 25 degrees  axial deflections at individual spinal
      segments (levels T5-T11) was measured using a custom needle deflection torque
      device attached to commercially available vertebral rotating construct. After the
      intact specimen was tested, torque measurements were repeated following a full
      facetectomy and posterior rib head resection RESULTS: Complete facetectomy
      resulted in an 18% decrease of torque needed to produce 25 degrees  of axial
      deformity compared to the intact specimen (P < 0.001). Rib resection added an
      additional 36% decrease in torque (P < 0.001). CONCLUSIONS: Complete
      facetectomies (Ponte or Smith-Petersen osteotomies) decrease the force required
      to rotate spinal segments with respect to the axial plane by approximately one
      fifth. Posterior rib head resection should be considered to further loosen the
      spine if additional axial correction is desired.

PMID- 22468155
TI  - The influence of brace type on the success rate of the Ponseti treatment protocol
      for idiopathic clubfoot.
AB  - PURPOSE: The success of the Ponseti method for treating idiopathic clubfoot
      deformity is dependent on the casting techniques and the adherence of the patient
      to the foot abduction brace protocol. Newly developed brace designs claim to be
      more comfortable, to be easier to use and to prevent dislodgement of the foot
      from the brace, making them more efficient and improving patient compliance. They
      are, however, more costly, and, therefore, accessible to fewer patients. We
      compared the compliance and treatment outcome using two brace designs, the
      traditional simple brace of pre-walking shoes attached to a Dennis Browne (DB)
      bar and the new sophisticated Mitchell brace. METHODS: We compared the functional
      outcome and compliance with the post-corrective bracing protocol of 38 children
      with idiopathic clubfoot treated in our institution using two brace designs.
      Twenty-one chose the DB brace and 17 chose the Mitchell brace. RESULTS: There was
      no difference in the compliance rate or in the final clinical and radiological
      outcomes of the two groups after a minimum of 2 years of follow-up. A positive
      correlation was found between the Pirani score at the beginning of treatment and
      the final functional score for both groups. Both groups were satisfied with the
      selected brace. Both groups were equally compliant with the brace protocol.
      CONCLUSION: We conclude that new and more expensive brace designs do not
      necessarily provide better clinical results. Fully corrected foot and a strong
      family-treating team partnership are crucial to adherence with the brace
      protocol.

PMID- 22468156
TI  - The use of the reconstruction plate in multiplanar tibial osteotomies in
      children.
AB  - PURPOSE: External fixation and cross-pin fixation appear to be the two most
      commonly used forms of fixation after a tibial osteotomy in children described in
      the literature. The purpose of this study is to describe our experience using a
      properly bent and contoured reconstruction plate for mismatched surfaces after a
      multiplanar tibial osteotomy. METHODS: A retrospective review was conducted of 37
      multiplanar tibial osteotomy surgeries in 23 children performed by a single
      surgeon using a reconstruction plate for internal fixation. A low fibular
      osteotomy and tibial osteotomy that required contouring and shaping of the plate
      were performed in all cases. A proximal tibial osteotomy was performed in 30
      cases and a distal osteotomy in seven cases. All cases were reinforced with a
      long-leg cast. All charts were reviewed for intra- and postoperative
      complications. The surgery using the reconstruction plate internal fixation was
      considered to be a success if there was healing of the osteotomy and no hardware
      failure. RESULTS: A properly bent and contoured reconstruction plate conformed
      well to the mismatched surfaces after tibial osteotomy. Hardware was removed in
      all but two cases, on average 7 months after surgery. There were no hardware
      failures. No child developed a deep wound infection or neurovascular
      complication, including compartment syndrome. Only two complications in 37
      surgeries (5%) were encountered and were typical of any type of internal
      fixation. One child required an exploratory procedure because of screw extrusion
      and one child developed a post-plate removal fracture. CONCLUSIONS: The
      reconstruction plate is very malleable and can be contoured to fit in nearly
      every direction to accommodate mismatched appositional surfaces. It has been
      successfully employed in 37 consecutive cases of multiplanar tibial osteotomy in
      children with relatively few complications, none directly related to the plate.

PMID- 22468157
TI  - Taylor spatial frame in the treatment of neglected fractures.
AB  - BACKGROUND: The Taylor spatial frame (TSF, Smith and Nephew, Memphis, TN, USA) is
      a modern multiplanar external fixator that combines ease of application and
      computer accuracy. Many patients in our geographic area seek treatment for their
      fractures by traditional bonesetters and present in the middle of treatment with
      neglected malaligned fractures. These fractures were an average of 10 weeks old
      (range 6-14 weeks) fractures with callus that were allowed to heal in a poor
      position. The spatial frame is applied easily on the fracture bone fragments. The
      accuracy of fracture reduction and deformity correction is dependant on analyzing
      anteroposterior and lateral radiographs of the fracture. Our experience with this
      external fixator in the treatment of neglected fractures is summarized. METHOD:
      Over a period of 6 years, the TSF was used in 24 neglected fracture cases which
      were collected from our prospective external fixator data base. All cases were
      followed for a minimum of 3 years. The data base and radiographs were reviewed in
      order to obtain demographic data, malalignment parameters, final correction, time
      in the TSF, and complications. RESULT: The patients' ages ranged from 6 to 18
      years. All were neglected fractures. The average delay in treatment was 10 weeks
      (range 6-14 weeks). All patients had closed osteoclasis. The time spent in the
      TSF varied according to the patient age and bone involved. Ten femoral and 14
      tibial fractures were included. Ten patients had superficial pin site infections
      that resolved with oral antibiotics. Postoperatively, no patient was noted to be
      more than 5 degrees  malrotated on clinical examination and no functional leg
      length discrepancy was observed. All of the fractures united. CONCLUSION:
      Anatomic alignment was achieved in all tibial fracture patients. At the final
      follow-up, fracture angulation and shortening were fully corrected, and some
      translational malalignment persisted in 67% of femur fractures. The TSF is an
      effective definitive method for the treatment of neglected fractures. LEVEL OF
      EVIDENCE: IV.

PMID- 22468158
TI  - Congenital dislocation of the knee: a protocol for management based on degree of
      knee flexion.
AB  - PURPOSE: Congenital dislocation of the knee (CDK) is a relatively rare condition.
      It may occur as an isolated deformity, it may be associated with musculoskeletal
      anomalies such as developmental dysplasia of the hip and clubfoot, or it may
      occur as part of a syndrome such as arthrogryposis multiplex congenita or Larsen
      syndrome, or it may occur in paralytic conditions such as meningomyelocele.
      Treatment options include serial casting, percutaneous quadriceps recession (PQR)
      and V-Y quadricepsplasty (VYQ). The aim of this study is to evaluate the medium
      term results of PQR and VYQ, and to set a protocol of management for CDK based on
      a modified grading system. METHODS: Eleven infants with 21 CDK were treated at
      our unit. Five knees were treated with serial casting, 12 knees with PQR and four
      knees with VYQ. Follow up averaged 41 months. RESULTS: Twelve knees achieved
      excellent results, seven knees achieved good results and two knees achieved fair
      results. CONCLUSION: A modified grading system for CDK is introduced. Based on
      this, we recommend the following. Serial casting is performed in patients with GI
      CDK. In GII CDK in neonates (babies up to the age of 1 month) serial casting is
      started. A maximum of four weekly manipulations and castings are attempted. If a
      range of flexion >90 degrees  is achieved, serial casting is continued; if range
      of flexion remains <90 degrees  it is necessary to proceed to PQR. In babies
      older than 1 month when first seen; PQR is performed from the start. VYQ is
      indicated in patients with GIII CDK or in recurrent cases.

PMID- 22468159
TI  - Distance from the growth plate and Its relation to the outcome of unicameral bone
      cyst treatment.
AB  - BACKGROUND: Interventions to treat unicameral bone cysts vary. Nonetheless,
      regardless of the intervention modality, the outcome is not certain. The purpose
      of this study was to determine if the distance between the growth plate and the
      cyst can be used to predict the outcome of the treatment. METHODS AND MATERIALS:
      Retrospectively, we assessed the outcome of 39 interventions in nineteen children
      that were performed between 1994 and 2003. Seventeen different modalities of
      treatment were employed. There were three female and sixteen male patients. The
      average age was 8 years. Nine cysts were in the greater trochanter area, three
      were in the femoral capital area and seven were in the proximal humerus.
      According to the cyst's distance from the growth plate, at the intervention time,
      there were 18 cases within less than 2 cm and 21 cases of more than 2 cm.
      RESULTS: Complete healing was achieved in 10 children (employing seven different
      modalities). In nine of them, the cysts were more than 2 cm away from the growth
      plate. In one child, the cyst was within less than 2 cm of the growth plate,
      however, treatment here involved epiphyseodesis. DISCUSSION: This study confirmed
      that, regardless of intervention modality, complete healing was not achievable in
      those cysts that are within less than 2 cm of an active growth plate. Complete
      healing was possible in those cysts that are more than 2 cm away from the growth
      plate. CONCLUSION: The 2-cm distance from the growth plate could be used as a
      predictor of treatment outcome of unicameral bone cysts.

PMID- 22468160
TI  - In Vivo Multiphoton Microscopy for Investigating Biomechanical Properties of
      Human Skin.
AB  - The biomechanical properties of living cells depend on their molecular building
      blocks, and are important for maintaining structure and function in cells, the
      extracellular matrix, and tissues. These biomechanical properties and forces also
      shape and modify the cellular and extracellular structures under stress. While
      many studies have investigated the biomechanics of single cells or small
      populations of cells in culture, or the properties of organs and tissues, few
      studies have investigated the biomechanics of complex cell populations in vivo.
      With the use of advanced multiphoton microscopy to visualize in vivo cell
      populations in human skin, the biomechanical properties are investigated in a
      depth-dependent manner in the stratum corneum and epidermis using quasi-static
      mechanical deformations. A 2D elastic registration algorithm was used to analyze
      the images before and after deformation to determine displacements in different
      skin layers. In this feasibility study, the images and results from one human
      subject demonstrate the potential of the technique for revealing differences in
      elastic properties between the stratum corneum and the rest of the epidermis.
      This interrogational imaging methodology has the potential to enable a wide range
      of investigations for understanding how the biomechanical properties of in vivo
      cell populations influence function in health and disease.

PMID- 22468161
TI  - Clinical Summarization Capabilities of Commercially-available and Internally
      developed Electronic Health Records.
AB  - OBJECTIVE: Clinical summarization, the process by which relevant patient
      information is electronically summarized and presented at the point of care, is
      of increasing importance given the increasing volume of clinical data in
      electronic health record systems (EHRs). There is a paucity of research on
      electronic clinical summarization, including the capabilities of currently
      available EHR systems.  METHODS: We compared different aspects of general
      clinical summary screens used in twelve different EHR systems using a previously
      described conceptual model: AORTIS (Aggregation, Organization, Reduction,
      Interpretation and Synthesis).  RESULTS: We found a wide variation in the EHRs'
      summarization capabilities: all systems were capable of simple aggregation and
      organization of limited clinical content, but only one demonstrated an ability to
      synthesize information from the data.  CONCLUSION: Improvement of the clinical
      summary screen functionality for currently available EHRs is necessary. Further
      research should identify strategies and methods for creating easy to use, well
      designed clinical summary screens that aggregate, organize and reduce all
      pertinent patient information as well as provide clinical interpretations and
      synthesis as required.

PMID- 22468162
TI  - Association of Birth Weight with Health and Long-Term Survival up to Middle and
      Old Ages in China.
AB  - This study is based on an unique dataset of birth records of 11,693 persons born
      in Beijing, China from 1921-54 and from clinical examinations (May 2003-April
      2005) of 2,085 tracked surviving cohort members (aged 50-82) to diagnose seven
      major chronic diseases. Data were analyzed using the extended Fixed Attribute
      Dynamics (FAD) method and multivariate regressions. The results of our FAD
      analysis have shown that, as compared to the persons with low birth weight
      (<2,500 g), the probability of survival from age 0 to ages 50-56, 63-67 and 68-82
      for persons with higher birth weight (2,500-2,999 g, 3,000-3499 g, or >=3,500 g)
      was 16-31, 62-104, and 52-108% higher respectively. These estimates display
      similar patterns for both genders, with somewhat stronger effects in men. Of the
      27 estimates of the Odds Ratio of Survival in the FAD analysis, 21 are
      statistically significant. Controlling for 14 confounding factors, multivariate
      binary logistic regressions have demonstrated that the risk of having
      cardiovascular disease and diabetes is negatively associated birth weight;
      ordinal logit regressions have shown that the number of major chronic diseases at
      ages 50-82 is significantly associated with birth weight: the lower the birth
      weight, the higher the risk of having more chronic diseases. We conclude that low
      birth weight is negatively associated with 1) long-term survival probability from
      age 0 to ages 50-82, and 2) overall health at middle and old ages. Further
      research is needed to understand the mechanisms of these effects.

PMID- 22468163
TI  - ERROR-FREE MILESTONES IN ERROR PRONE MEASUREMENTS.
AB  - A predictor variable or dose that is measured with substantial error may possess
      an error-free milestone, such that it is known with negligible error whether the
      value of the variable is to the left or right of the milestone. Such a milestone
      provides a basis for estimating a linear relationship between the true but
      unknown value of the error-free predictor and an outcome, because the milestone
      creates a strong and valid instrumental variable. The inferences are
      nonparametric and robust, and in the simplest cases, they are exact and
      distribution free. We also consider multiple milestones for a single predictor
      and milestones for several predictors whose partial slopes are estimated
      simultaneously. Examples are drawn from the Wisconsin Longitudinal Study, in
      which a BA degree acts as a milestone for sixteen years of education, and the
      binary indicator of military service acts as a milestone for years of service.

PMID- 22468164
TI  - Joint rare variant association test of the average and individual effects for
      sequencing studies.
AB  - For many complex traits, single nucleotide polymorphisms (SNPs) identified from
      genome-wide association studies (GWAS) only explain a small percentage of
      heritability. Next generation sequencing technology makes it possible to explore
      unexplained heritability by identifying rare variants (RVs). Existing tests
      designed for RVs look for optimal strategies to combine information across
      multiple variants. Many of the tests have good power when the true underlying
      associations are either in the same direction or in opposite directions. We
      propose three tests for examining the association between a phenotype and RVs,
      where two of them jointly consider the common association across RVs and the
      individual deviations from the common effect. On one hand, similar to some of the
      best existing methods, the individual deviations are modeled as random effects to
      borrow information across multiple RVs. On the other hand, unlike the existing
      methods which pool individual effects towards zero, we pool them towards a
      possibly non-zero common effect by adding a pooled variant into the model. The
      common effect and the individual effects are jointly tested. We show through
      extensive simulations that at least one of the three tests proposed here is the
      most powerful or very close to being the most powerful in various settings of
      true models. This is appealing in practice because the direction and size of the
      true effects of the associated RVs are unknown. Researchers can apply the
      developed tests to improve power under a wide range of true models.

PMID- 22468165
TI  - The double-edged sword: How evolution can make or break a live-attenuated virus
      vaccine.
AB  - Even students who reject evolution are often willing to consider cases in which
      evolutionary biology contributes to, or undermines, biomedical interventions.
      Moreover the intersection of evolutionary biology and biomedicine is fascinating
      in its own right. This review offers an overview of the ways in which evolution
      has impacted the design and deployment of live-attenuated virus vaccines, with
      subsections that may be useful as lecture material or as the basis for case
      studies in classes at a variety of levels. Live- attenuated virus vaccines have
      been modified in ways that restrain their replication in a host, so that
      infection (vaccination) produces immunity but not disease. Applied evolution, in
      the form of serial passage in novel host cells, is a "classical" method to
      generate live-attenuated viruses. However many live-attenuated vaccines exhibit
      reversion to virulence through back-mutation of attenuating mutations,
      compensatory mutations elsewhere in the genome, recombination or reassortment, or
      changes in quasispecies diversity. Additionally the combination of multiple live
      attenuated strains may result in competition or facilitation between individual
      vaccine viruses, resulting in undesirable increases in virulence or decreases in
      immunogenicity. Genetic engineering informed by evolutionary thinking has led to
      a number of novel approaches to generate live-attenuated virus vaccines that
      contain substantial safeguards against reversion to virulence and that ameliorate
      interference among multiple vaccine strains. Finally, vaccines have the potential
      to shape the evolution of their wild type counterparts in counter-productive
      ways; at the extreme vaccine-driven eradication of a virus may create an empty
      niche that promotes the emergence of new viral pathogens.

PMID- 22468166
TI  - Effects of Histone Deacetylase Inhibitors on Modulating H3K4 Methylation Marks -
      A Novel Cross-Talk Mechanism between Histone-Modifying Enzymes.
AB  - A recent study reports that histone deacetylase (HDAC) inhibitors, AR42 and MS-
      275, upregulated H3K4 methylation marks in prostate cancer cells, leading to
      transcriptional activation of genes including those associated with roles in
      tumor suppression and cell differentiation (1). Evidence suggests that the
      crosstalk between histone deacetylation and histone H3K4 methylation is
      attributable to the ability of these HDAC inhibitors to repress the JARID1 family
      of histone H3 lysine 4 demethylases (H3K4DMs), including RBP2, PLU-1, SMCX, and
      LSD1, through the downregulation of Sp1 expression. This demonstrates the
      complexity of the functional roles of HDACs in the regulation of histone
      modifications as well as the activation of epigenetically silenced gene
      expression. Equally important is the ability of HDAC inhibitors to
      transcriptionally suppress H3K4DM gene expression which has therapeutic
      implications, in that several H3K4DMs such as LSD1 and PLU-1 have been implicated
      in the pathogenesis of many types of malignancies.

PMID- 22468167
TI  - MicroRNAs: Processing, Maturation, Target Recognition and Regulatory Functions.
AB  - The remarkable discovery of small noncoding microRNAs (miRNAs) and their role in
      posttranscriptional gene regulation have revealed another fine-tuning step in the
      expression of genetic information. A large number of cellular pathways, which act
      in organismal development and are important in health and disease, appear to be
      modulated by miRNAs. At the molecular level, miRNAs restrain the production of
      proteins by affecting the stability of their target mRNA and/or by down
      regulating their translation. This review attempts to offer a snapshot of aspects
      of miRNA coding, processing, target recognition and function in animals. Our goal
      here is to provide the readers with a thought-provoking and mechanistic
      introduction to the miRNA world rather than with a detailed encyclopedia.

PMID- 22468168
TI  - MicroRNAs and Androgen Receptor 3' Untranslated Region: A Missing Link in
      Castration-resistant Prostate Cancer?
AB  - The ligand-activated transcription factor, androgen receptor (AR) plays a central
      role in the development and progression of prostate cancer. Prostate cancer
      initiates as an androgen-dependent disease and further accumulation of multiple
      sequential genetic and epigenetic alterations transform it into an aggressive,
      castration-resistant prostate cancer (CRPC). The molecular basis of the
      transition from androgen-dependent prostate cancer to CRPC remains unclear.
      However, it is apparent that AR plays a pivotal role in this alteration. The
      recent discovery that microRNAs (miRNAs) can target the function of AR suggests a
      functional role of these non-coding RNAs in the pathogenesis of prostate cancer.
      miRNAs usually function by targeting the 3' untranslated region (UTR) of a mRNA
      by base-pairing interactions and modulate translation either by destabilizing the
      message or by repression of protein synthesis in actively translating ribosomes.
      Here, we discuss the potential molecular pathways through which AR targeting
      miRNAs may promote CRPC. Modulation of AR expression by miRNAs presents a novel
      therapeutic option for prostate cancer, albeit it will likely be used in
      combination with the existing therapies.

PMID- 22468169
TI  - Using Ascertainment for Targeted Resequencing to Increase Power to Identify
      Causal Variants.
AB  - Researchers continue to use genome-wide association studies (GWAS) to find the
      genetic markers associated with disease. Recent studies have added to the typical
      two-stage analysis a third stage that uses targeted resequencing on a randomly
      selected subset of the cases to detect the causal single-nucleotide polymorphism
      (SNP). We propose a design for targeted resequencing that increases the power to
      detect the causal variant. The design features an ascertainment scheme wherein
      only those cases with the presence of a risk allele are selected for targeted
      resequencing. We simulated a disease with a single causal SNP to evaluate our
      method versus a targeted resequencing design using randomly selected individuals.
      The simulation studies showed that ascertaining individuals for the targeted
      resequencing can substantially increase the power to detect a causal SNP, without
      increasing the false-positive rate.

PMID- 22468170
TI  - Impact of Baseline Disease Severity Over 26 and 52 Weeks of Treatment with
      Calcitriol Ointment 3ug/g in Patients with Mild-to-moderate Plaque Psoriasis.
AB  - OBJECTIVE: Calcitriol 3ug/g ointment has been shown to be a safe and effective
      treatment for adults with mild-to-moderate plaque psoriasis. This analysis
      evaluated the response to calcitriol 3ug/g ointment relative to baseline disease.
      DESIGN: Retrospective analysis of data from a 12-month safety and tolerability
      trial. SETTING AND PARTICIPANTS: At baseline, 40.1 percent (130/324) of patients
      had an affected body surface area of 11 to 20 percent, and 55.2 percent (179/324)
      had moderate and 25.9 percent (84/324) had severe disease according to global
      severity score. Patients applied calcitriol 3ug/g ointment twice daily for up to
      52 weeks. MEASUREMENTS: Change in investigator's global severity scores and
      involved body surface area at Week 26 (N=249) and Week 52 (N=130) relative to
      baseline. RESULTS: Compared with baseline, most patients experienced at least a 1
      grade improvement in global severity score at Weeks 26 (195/249, 78.3%) and 52
      (109/130, 83.8%). Stabilization (i.e., no change in global severity score) was
      reported in 19.3 percent (48/249) at Week 26 and in 12.3 percent (16/130) at Week
      52. Most patients also experienced at least a 1-grade improvement in body surface
      area involved at Weeks 26 (152/249, 61.0%) and 52 (95/130, 73.1%). Stabilization
      (no change in affected body surface area) was reported in 32.5 percent (81/249)
      at Week 26 and 24.6 percent (32/130) at Week 52. The proportion of patients
      experiencing improvement in global severity score and body surface area was
      comparable across all categories of severity and disease extent at baseline.
      CONCLUSION: This analysis suggests that calcitriol 3ug/g ointment use for 26
      weeks (N=249) and 52 weeks (N=130) was associated with disease improvement or
      stabilization in most patients with plaque psoriasis.

PMID- 22468171
TI  - Effect of Sinecatechins on HPV-Activated Cell Growth and Induction of Apoptosis.
AB  - BACKGROUND: Green tea catechins possess a wide range of pharmacological
      properties, including antiviral, anti-infective, and immunostimulatory
      properties. They also have demonstrated inhibitory effects on a variety of
      enzymatic and metabolic pathways involved in cancer development. Catechins have
      been shown to have antiproliferative properties in various cell lines and may
      have direct virucidal effect. The United States Food and Drug Administration has
      approved a topical ointment formulation of sinecatechins, derived from green tea
      catechins and other tea components, for the treatment of external genital and
      perianal warts. The exact mechanism of action of sinecatechins in eradication of
      human papillomavirus-induced external genital and perianal warts is unknown, but
      may be due to one or more of the mechanisms mentioned. OBJECTIVE: This study was
      conducted to investigate the growth inhibitory potential of the sinecatechins in
      human cervical carcinoma cell lines infected with human papillomavirus. METHODS:
      The viability of tumor cell lines (CaSki and SiHa infected with human
      papillomavirus-16; HeLa and C4-I infected with human papillomavirus-18) was
      investigated as one parameter in a short-term viability assay (48 hours). This
      was followed by a long-term clonogenic assay (12-23 days) to determine the
      cytotoxic potential of sinecatechins as a parameter for cell viability and
      proliferation. This assay determined if the effect observed in the viability
      assay was due to retardation in cell proliferation or to a reduction of total
      cell number, leading to cell death. RESULTS: Based on the data collected,
      sinecatechins inhibited cell growth in all four tumor cell lines by 50 percent
      (GI(50)) at concentrations ranging from 160 to 360uM. C4-I cells were the most
      sensitive to treatment with sinecatechins, with a lower GI(50) (~34uM). Total GI
      was achieved in a 48-hour assay at 625uM sinecatechins (40uM for C4-I), with
      growth inhibitory potential detectable after one hour. Clonogenic assays
      confirmed the cytotoxic potential of sinecatechins with a reduction in clone
      numbers in a concentration-dependent fashion. Sinecatechins substantially reduced
      the number of surviving HeLa cells at a concentration of 200uM, while surviving
      SiHa cells were almost totally eradicated with a concentration of 600uM.
      CONCLUSION: Sinecatechins demonstrated growth inhibitory potential in all four
      human papillomavirus-infected tumor cell lines, which may be attributed to the
      induction of apoptosis, mediated by cell cycle deregulation. In addition, this
      antiproliferative effect may contribute to the overall cancer-preventative
      function and possible direct antiviral activity of sinecatechins that may
      contribute to external genital and perianal warts clearance.

PMID- 22468172
TI  - Effect of 635nm Low-level Laser Therapy on Upper Arm Circumference Reduction: A
      Double-blind, Randomized, Sham-controlled Trial.
AB  - OBJECTIVE: To assess the safety and efficacy of low-level laser therapy as a
      noninvasive method for reducing upper arm circumference. DESIGN: Randomized,
      double-blind study whereby healthy subjects (N=40) with a body mass index of 20
      to 35kg/m(2) received three 20-minute low-level laser therapy (N=20) or sham
      treatments (N=20) each week for two weeks. MEASUREMENTS: Upper arm circumference
      was measured after three and six treatments and two weeks post-treatment. Primary
      success criterion was the proportion of subjects achieving a combined reduction
      in arm circumference of >=1.25cm measured at three equally spaced points between
      the elbow and the shoulder. Secondary outcomes included total measurement change
      at each time point and subjective satisfaction ratings. RESULTS: After six
      treatments, the low-level laser therapy group showed a combined reduction in arm
      circumference of 3.7cm versus 0.2cm in the sham treatment group (p<0.0001).
      Significantly more subjects in the low-level laser therapy group (N=12; 60%)
      achieved >=1.5cm total decrease in upper arm circumference versus sham-treated
      subjects (N=0; 0%) (p<0.0005). Low-level laser therapy treatment resulted in a
      combined reduction in arm circumference of 2.2cm after three treatments and 3.7cm
      after six treatments (for each, p<0.0001) indicating a progressive and cumulative
      treatment effect. Body mass index remained unchanged for all subjects. A
      significantly greater number of subjects in the low-level laser therapy treatment
      group were satisfied with their results (p<0.05), believed their upper arm
      appearance improved (p<0.0005), and indicated the results exceeded expectations
      (p<0.05). The treatments were painless and no adverse events were reported.
      CONCLUSION: Noninvasive low-level laser therapy is safe, painless, and effective
      in reducing upper arm circumference and is associated with a high degree of
      subject satisfaction.

PMID- 22468173
TI  - Tinea capitis in infants: recognition, evaluation, and management suggestions.
AB  - Tinea capitis is a reasonably common infection among the pediatric population;
      however, it is still a relatively rare entity among infants less than one year of
      age. As such, a high index of suspicion is necessary for diagnosis among infants
      and an appropriate diagnostic work up should be employed in any case where a
      dermatophyte infection is suspected. Several methods are available for diagnosis.
      In addition, proper identification of the specific dermatophyte genera involved
      should be considered as treatment options may be altered based on the causative
      pathogen identified.

PMID- 22468174
TI  - Acrodermatitis continua of hallopeau successfully treated with adalimumab.
AB  - Acrodermatitis continua of Hallopeau, first described by Hallopeau in 1890, is an
      uncommon variant of pustular psoriasis. Acrodermatitis continua of Hallopeau
      presents as sterile pustules on the hands and feet. It has a relapsing course.
      Although acrodermatitis continua of Hallopeau is a pustular psoriasis variant,
      the condition is not easily treated with antipsoriatic medications. In the
      following case, the authors report a case of acrodermatitis continua of Hallopeau
      successfully treated with adalimumab. In addition, the cases of acrodermatitis
      continua of Hallopeau treated with tumor necrosis-alpha inhibitors are
      summarized.

PMID- 22468175
TI  - Neurotic excoriations: a diagnosis of exclusion.
AB  - Patients with psychiatric disease may use the skin as a means of communication
      during times of increased emotional distress. Furthermore, a high incidence of
      skin disorders among patients with a primary psychiatric condition, including
      depression, schizophrenia, and anxiety, has been demonstrated, with neurotic
      excoriation being one of the most commonly diagnosed. Despite the strong
      association and incidence of psychogenic excoriation in patients with a primary
      psychiatric disorder, it is important for primary care physicians and
      dermatologists alike to realize that these patients may have true dermatological
      disease. The authors present a 53-year-old woman with past medical history
      significant for schizophrenia, depression, hepatitis C, and diabetes mellitus
      type II, who was transferred from an outside hospital secondary to anemia in
      association with diffuse skin lesions. Although she adamantly denied self
      inducing the skin lesions, she was diagnosed with neurotic excoriations by
      primary care and specialty care physicians on three different occasions. After a
      thorough workup during this admission, the patient was diagnosed with bullous
      pemphigoid.

PMID- 22468176
TI  - Advances in understanding and managing rosacea: part 1: connecting the dots
      between pathophysiological mechanisms and common clinical features of rosacea
      with emphasis on vascular changes and facial erythema.
AB  - Rosacea is a common inflammatory facial dermatoses affecting primarily adults
      with fair skin, although all skin types may be affected. The diagnostic term
      "rosacea" reflects a spectrum of clinical features with the more common
      presentations characterized by increased blood flow and vasodilation during
      disease flares, which accentuate central facial erythema. Inflammatory lesions,
      usually papules and/or pustules are present in some cases. Variations in
      magnitude of the associated features of rosacea are noted clinically. Over time,
      other clinical features emerge or may be further accentuated, such as diffuse
      facial erythema and telangiectasias, as fixed changes in cutaneous vasculature
      occur. These later findings account for persistent diffuse facial erythema
      usually accentuated centrally on the inner cheeks, chin, nose, and/or medial
      forehead. Some patients may also develop phymatous changes and/or have concurrent
      ocular rosacea. Augmented innate immune response to certain triggers (often
      exogenous) and neurovascular/neuroimmune dysregulation appear to be involved
      early in the pathophysiological sequence of cutaneous rosacea and appear to
      signal other downstream inflammatory or physiochemical cascades that contribute
      to the pathogenesis of the disorder. In this article, Part 1 of a two-part
      series, emphasis is placed upon the correlation of clinical features and
      underlying pathophysiological changes in the more common presentations of rosacea
      encountered by the clinician. The importance of this information is that some of
      these pathogenic mechanisms are modulated by available therapies, and others
      remain as targets for the development of new therapeutic agents or modalities.

PMID- 22468177
TI  - Advances in understanding and managing rosacea: part 2: the central role,
      evaluation, and medical management of diffuse and persistent facial erythema of
      rosacea.
AB  - In this article, the second part of a two-part series on rosacea, emphasis will
      be placed on persistent facial erythema. Despite variations in the intensity of
      visible redness, persistent facial erythema is a very common and consistent
      finding among patients with rosacea, including those with presentations
      classically defined as papulopustular rosacea, erythematotelangiectatic rosacea,
      and in many patients with phymatous rosacea. The underlying mechanisms of rosacea
      and their correlation with specific clinical features have been discussed in Part
      1 and are referred to here where applicable. An overview of cutaneous
      vasculature, role of alpha-adrenoreceptors, and a discussion of available medical
      therapies and treatment selection are also presented, including emerging topical
      options for diffuse and persistent facial erythema of rosacea.

PMID- 22468178
TI  - Oral Spironolactone in Post-teenage Female Patients with Acne Vulgaris: Practical
      Considerations for the Clinician Based on Current Data and Clinical Experience.
AB  - Oral spironolactone has been used for over two decades in the dermatological
      setting. Although it is not generally considered a primary option in the
      management of female patients with acne vulgaris, the increase in office visits
      by post-teenage women with acne vulgaris has recently placed a spotlight on the
      use of this agent in this subgroup of patients. This article reviews the
      literature focusing on the use of oral spironolactone in this subset of women
      with acne vulgaris, including discussions of the recommended starting dose,
      expected response time, adjustments in therapy, potential adverse effects, and
      patient monitoring.

PMID- 22468179
TI  - A Four-question Approach to Determining the Impact of Acne Treatment on Quality
      of Life.
AB  - Facial acne vulgaris can have profound effects on health-related quality of life.
      In some studies, patients with acne vulgaris reported results similar to those
      noted with other chronic diseases, such as asthma, arthritis, or diabetes.
      Clinical objective assessments alone do not adequately capture the impact of acne
      vulgaris severity from a patient's perspective. Health-related quality-of-life
      assessment is important in order to fully characterize the overall burden of
      disease and effectiveness of treatment as the perspectives of the patient are
      also taken into account. Previous studies of the impact of acne vulgaris
      treatment on health-related quality of life have been limited in their scope of
      assessment. Drawbacks of prior studies have included small numbers of patients,
      health-related quality-of-life parameters that were not adequately evaluated,
      inclusion of only a limited range of mild-to-moderate acne vulgaris severity, or
      being unblinded or observational in study design. The Acne Quality of Life is an
      acne-specific questionnaire developed to assess treatment impact on the health
      related quality of life of patients with acne vulgaris. Its psychometric
      properties and degree of responsiveness are well-established. Improvement in Acne
      Quality of Life with the fixed combination clindamycin phosphate 1.2%/benzoyl
      peroxide 2.5% aqueous gel in the largest cohort of acne vulgaris patients where
      health-related quality of life was studied has been reported recently.
      Significant improvements in all four domains over 12 weeks were seen with
      clindamycin phosphate 1.2%/benzoyl peroxide 2.5% aqueous gel compared to patients
      treated with individual active ingredients or vehicle (p<0.001). Length and time
      required for completion of the 19-item Acne Quality of Life questionnaire is
      likely to preclude its use in clinical practice. A condensed, validated Acne Q-4
      scale based on the four items most broadly representative of health-related
      quality of life combined with a high level of correlation to the Acne Quality of
      Life questionnaire has been suggested as a more realistic approach that may be
      applied by clinicians when managing patients with acne vulgaris. The authors
      present data on the effectiveness of clindamycin phosphate 1.2%/benzoyl peroxide
      2.5% aqueous gel on health-related quality of life based on this Acne Q-4 scale.

PMID- 22468180
TI  - Dynamic culture improves MSC adhesion on freeze-dried bone as a scaffold for bone
      engineering.
AB  - AIM: To investigate the interaction between mesenchymal stem cells (MSCs) and
      bone grafts using two different cultivation methods: static and dynamic. METHODS:
      MSCs were isolated from rat bone marrow. MSC culture was analyzed according to
      the morphology, cell differentiation potential, and surface molecular markers.
      Before cell culture, freeze-dried bone (FDB) was maintained in culture for 3 d in
      order to verify culture medium pH. MSCs were co-cultured with FDB using two
      different cultivation methods: static co-culture (two-dimensional) and dynamic co
      culture (three-dimensional). After 24 h of cultivation by dynamic or static
      methods, histological analysis of Cell adhesion on FDB was performed. Cell
      viability was assessed by the Trypan Blue exclusion method on days 0, 3 and 6
      after dynamic or static culture. Adherent cells were detached from FDB surface,
      stained with Trypan Blue, and quantified to determine whether the cells remained
      on the graft surface in prolonged non-dynamic culture. Statistical analyses were
      performed with SPSS and a P < 0.05 was considered significant. RESULTS: The
      results showed a clear potential for adipogenic and osteogenic differentiation of
      MSC cultures. Rat MSCs were positive for CD44, CD90 and CD29 and negative for
      CD34, CD45 and CD11bc. FDBs were maintained in culture for 3 d and the results
      showed there was no significant variation in the culture medium pH with FDB
      compared to pure medium pH (P > 0.05). In histological analysis, there was a
      significant difference in the amount of adhered cells on FDB between the two
      cultivation methods (P < 0.05). The MSCs in the dynamic co-culture method
      demonstrated greater adhesion on the bone surface than in static co-culture
      method. On day 0, the cell viability in the dynamic system was significantly
      higher than in the static system (P < 0.05). There was a statistical difference
      in cell viability between days 0, 3 and 6 after dynamic culture (P < 0.05). In
      static culture, cell viability on day 6 was significantly lower than on day 3 and
      0 (P < 0.05). CONCLUSION: An alternative cultivation method was developed to
      improve the MSCs adhesion on FDB, demonstrating that dynamic co-culture provides
      a superior environment over static conditions.

PMID- 22468181
TI  - Follow-up of intestinal metaplasia in the stomach: When, how and why.
AB  - Gastric cancer remains the second most frequent cause of cancer-related mortality
      in the world. Screening programs in some Asian countries are impractical in the
      majority of other countries worldwide. Therefore, follow-up of precancerous
      lesions is advisable for secondary gastric cancer prevention. Intestinal
      metaplasia (IM) is recognized as a precancerous lesion for gastric cancer,
      increasing the risk by 6-fold. IM is highly prevalent in the general population,
      being detected in nearly 1 of every 4 patients undergoing upper endoscopy. The IM
      prevalence rate is significantly higher in patients with Helicobacter pylori (H.
      pylori) infection, in first-degree relatives of gastric cancer patients, in
      smokers and it increases with patient age. IM is the "breaking point" in the
      gastric carcinogenesis cascade and does not appear to regress following H. pylori
      eradication, although the cure of infection may slow its progression. Gastric
      cancer risk is higher in patients with incomplete-type IM, in those with both
      antral and gastric body involvement, and the risk significantly increases with IM
      extension over 20% of the gastric mucosa. Scheduled endoscopic control could be
      cost-effective in IM patients, depending on the yearly incidence of gastric
      cancer in IM patients, the stage of gastric cancer at diagnosis discovered at
      surveillance, and the cost of endoscopy. As a pragmatic behavior, yearly
      endoscopic control would appear justified in all IM patients with at least one of
      these conditions: (1) IM extension > 20%; (2) the presence of incomplete type IM;
      (3) first-degree relative of gastric cancer patients; and (4) smokers. In the
      remaining IM patients, a less intensive (2-3 years) could be proposed.

PMID- 22468182
TI  - Patients with hematological malignancies and serological signs of prior resolved
      hepatitis B.
AB  - Hepatitis B virus (HBV) infection affects a large part of the world population.
      Within the different virological HBV categories that have been identified,
      patients with occult HBV infection represent a peculiar group. These individuals
      harbor a replication competent virus, inhibited in its replicative function.
      Accordingly, cases of reactivations have been observed in immunosuppressed
      individuals who lose immunological control over the infection. Patients with
      hematological malignancies (HM) are treated with intense myelo- and
      immunosuppressive chemotherapy regimens which favor HBV reactivation. This event
      can have severe consequences, such as hepatitis flare, hepatic failure and even
      death. In addition, it can lead to delays or interruptions of curative
      treatments, resulting in a decreased disease free and overall survival. In this
      review, we will examine the event of HBV reactivation in patients with signs of
      resolved HBV infection undergoing treatment for HM and propose possible
      management strategies.

PMID- 22468183
TI  - HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and
      open questions.
AB  - There is plenty of data confirming that hepatitis C virus (HCV) infection is a
      predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while
      relatively few reports have addressed the role of HCV in affecting B-NHL
      patients' outcome. HCV infection may influence the short-term outcome of B-NHL
      because of the emergence of severe hepatic toxicity (HT) during
      immunochemotherapy. Furthermore, the long term outcome of HCV-related liver
      disease and patients' quality of life will possibly be affected by Rituximab
      maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic
      stem cell transplantation. In this review, data dealing with aggressive and low
      grade B-NHL were separately analyzed. The few retrospective papers reporting on
      aggressive B-NHL patients showed that HCV infection is a risk factor for the
      outbreak of severe HT during treatment. This adverse event not infrequently leads
      to the reduction of treatment density and intensity. Existing papers report that
      low-grade B-NHL patients with HCV infection may have a more widespread disease,
      more frequent relapses or a lower ORR compared to HCV-negative patients.
      Notwithstanding that, there is no statistical evidence that the prognosis of HCV
      positive patients is inferior to that of HCV-negative subjects. HCV-positive
      prospective studies and longer follow-up are necessary to ascertain if HCV
      positive B-NHL patients have inferior outcomes and if there are long term sequels
      of immunochemotherapies on the progression of liver disease.

PMID- 22468184
TI  - Cancer stem cell hypothesis and gastric carcinogenesis: Experimental evidence and
      unsolved questions.
AB  - Traditionally, the clonal evolution model has been used to explain gastric cancer
      (GC) growth dynamics. According to this model, GC cells result from multiple
      mutations over time resulting in a population of continually diversifying cells.
      This heterogeneity enables the survival of different clones under particular
      conditions allowing growth at metastatic locations or resistance to
      chemotherapeutics. Cancer stem cell (CSC) theory completely overturns this
      traditional understanding of cancer suggesting that only CSCs can self-renew and
      promote tumor growth. CSCs are relatively refractory to conventional therapies,
      thus explaining why anti-cancer therapies are far from curative and why relapses
      of cancer are frequent. The identification of the CSC component of a tumor might,
      thus, open new therapeutic perspective based on the selective targeting of this
      small population of cells. In this review we examine the current scientific
      evidence supporting the existence of CSC in gastric tumors and analyze the main
      unsolved questions of this difficult field of cancer research.

PMID- 22468185
TI  - Tumors of ampulla of Vater: A case series and review of chemotherapy options.
AB  - Carcinomas of the Ampulla of Vater are rare tumors, accounting for 0.2% of
      gastrointestinal cancers. Compared with other biliary tract neoplasms, these
      tumors have a relatively favorable prognosis after surgical resection. Based on
      their epithelium of origin, two subtypes of ampullary carcinoma have been
      recently distinguished: intestinal and pancreatobiliary. This study evaluates
      histopathological features and outcomes of ampullary carcinoma and to compares
      the survival of these tumors to that of other biliary tract tumors. The
      chemotherapic options available for ampullary cancer are also reviewed. We
      analyzed data from 20 consecutive patients with ampullary carcinomas and 26
      patients with other biliary tract carcinomas, observed in our Institution.
      Statistical analysis was performed by using either Fisher's exact test or chi(2)
      test for categorical variables. Median time of survival was calculated and
      compared using the Log-Rank test. Similar distribution of demographic
      characteristics and stage between ampullary and other biliary tract cancers was
      observed. Patients with ampullary cancer underwent surgery more frequently than
      other biliary cancers while chemotherapy and radiotherapy were used equally. In
      accordance with the literature, a longer median survival was observed in the
      group of ampullary carcinomas.

PMID- 22468187
TI  - Dural lesions mimicking meningiomas: A pictorial essay.
AB  - The purpose of this essay was to illustrate the radiological and pathological
      findings in a wide spectrum of dural lesions mimicking meningiomas. Familiarity
      with and knowledge of these findings will narrow the differential diagnosis and
      provide guidance for patient management. In this pictorial review, we describe
      the following entities: Solitary fibrous tumors, hemangiopericytoma, gliosarcoma,
      leiomyosarcoma, dural metastases, Hodgkin's disease, plasmocytoma, Rosai-Dorfman
      disease, neurosarcoidosis, melanocytic neoplasms and plasma cell granuloma.

PMID- 22468186
TI  - Magnetic resonance diffusion-perfusion mismatch in acute ischemic stroke: An
      update.
AB  - The concept of magnetic resonance perfusion-diffusion mismatch (PDM) provides a
      practical and approximate measure of the tissue at risk and has been increasingly
      applied for the evaluation of hyperacute and acute stroke in animals and
      patients. Recent studies demonstrated that PDM does not optimally define the
      ischemic penumbra; because early abnormality on diffusion-weighted imaging
      overestimates the infarct core by including part of the penumbra, and the
      abnormality on perfusion weighted imaging overestimates the penumbra by including
      regions of benign oligemia. To overcome these limitations, many efforts have been
      made to optimize conventional PDM. Various alternatives beyond the PDM concept
      are under investigation in order to better define the penumbra. The PDM theory
      has been applied in ischemic stroke for at least three purposes: to be used as a
      practical selection tool for stroke treatment; to test the hypothesis that
      patients with PDM pattern will benefit from treatment, while those without
      mismatch pattern will not; to be a surrogate measure for stroke outcome. The main
      patterns of PDM and its relation with clinical outcomes were also briefly
      reviewed. The conclusion was that patients with PDM documented more reperfusion,
      reduced infarct growth and better clinical outcomes compared to patients without
      PDM, but it was not yet clear that thrombolytic therapy is beneficial when
      patients were selected on PDM. Studies based on a larger cohort are currently
      under investigation to further validate the PDM hypothesis.

PMID- 22468188
TI  - Cognitive and functional status after vein of Galen aneurysmal malformation
      endovascular occlusion.
AB  - AIM: To study the clinical outcomes of treating vein of Galen aneurysmal
      malformations (VGAM), we assessed our patient cohort using standardized cognitive
      and functional measures. METHODS: A retrospective review of patients with VGAM
      treated by a single practitioner between 2003 and 2009 was performed for this
      study. In addition to routine clinical assessment, all patients were evaluated
      for cognitive and functional impairment using validated measures including the
      Neurobehavioral Rating Scale-Revised, the Bicetre outcome score, and the Barthel
      index. RESULTS: Five patients underwent combined transarterial and transvenous
      embolization of their VGAM during the study period. VGAMs were classified based
      on angioarchitecture as either choroidal (1/5) or mural (4/5) according to the
      classification scheme of Lasjaunias. In total, 13 embolization procedures were
      performed consisting of 1 to 3 treatment stages per patient. Complete or near
      complete occlusion was achieved in 4 patients, while subtotal occlusion was
      achieved in 1 patient. During follow-up (median 62.6 mo), all patients were
      either unchanged or cognitively and neurologically intact. CONCLUSION: VGAM can
      be safely and effectively treated by staged transarterial and transvenous
      embolization. Using this strategy, excellent long-term cognitive and functional
      outcomes can be achieved.

PMID- 22468189
TI  - Assessment of gray matter heterotopia by magnetic resonance imaging.
AB  - AIM: To evaluate magnetic resonance imaging (MRI) features of different types of
      gray matter heterotopia. METHODS: Between June 2005 and December 2009, the
      medical records and MRI studies of patients with gray matter heterotopia were
      reviewed. The MRI morphologic findings of heterotopia were recorded along with
      the presence and type of associated cranial malformations. Available clinical and
      electrophysiological data were also recorded. RESULTS: 20 patients were included
      in the study. Their ages ranged from 9 mo to 39 years with a mean age of 15
      years. All patients suffered from epileptic seizures. According to the location
      of heterotopia, patients were classified into three groups: subependymal (12),
      subcortical (5) and band (3) heterotopia. CONCLUSION: MRI was useful in
      diagnosing and differentiating between various types of gray matter heterotopia.
      The severity of clinical manifestations of heterotopia was related to the
      location and pattern of heterotopia. Determination of heterotopia type and its
      extent is useful for management planning and predicting prognosis.

PMID- 22468190
TI  - Prediction of transitional lumbosacral anatomy on magnetic resonance imaging of
      the lumbar spine.
AB  - AIM: To evaluate two simple angle measurements for predicting lumbosacral
      transitional vertebra (LSTV) in magnetic resonance imaging (MRI) studies of the
      spine. METHODS: The lumbar spine MRI studies of 50 subjects with LSTV and 50
      subjects with normal lumbosacral anatomy were retrospectively evaluated. In each
      study, the mid-sagittal T2-weighted image was used to measure the angle formed by
      a line parallel to the superior surface of the sacrum and a line perpendicular to
      the axis of the scan table (A-angle), as well as the angle formed by a line
      parallel to the superior endplate of the L3 vertebra and a line parallel to the
      superior surface of the sacrum (B-angle). RESULTS: The total study population
      consisted of 100 subjects (46 males, 54 females, 51 +/- 16 years old). There were
      no differences in age and sex between the two groups. Both A-angle and B-angle
      were significantly increased in subjects with LSTV compared to controls (P <
      0.05). The optimal cut-off values of A-angle and B-angle for the prediction of
      LSTV were 39.8 degrees  (sensitivity = 80%, specificity = 80%, accuracy = 83%;
      95% confidence interval = 74%-89%, P = 0.0001) and 35.9 degrees  (sensitivity =
      80%, specificity = 54%, accuracy = 69%; 95% confidence interval = 59%-78%, P =
      0.0005), respectively. CONCLUSION: On sagittal MR images of the lumbar spine, an
      increased A-angle and/or B-angle should alert the radiologist to the presence of
      LSTV.

PMID- 22468191
TI  - Ablation margin assessment of liver tumors with intravenous contrast-enhanced C
      arm computed tomography.
AB  - AIM: To determine the influence of anthropomorphic parameters on the relationship
      between patient centering, mean computed tomography (CT) numbers and quantitative
      image noise in abdominal CT. METHODS: Our Institutional Review Board approved
      study included 395 patients (age range 21-108, years; male:female = 195:200) who
      underwent contrast-enhanced abdominal CT on a 16-section multi-detector row
      scanner (GE LightSpeed 16). Patient centering in the gantry isocenter was
      measured from the lateral localizer radiograph (off center S = patient off
      centered superior to isocenter; off center I = patient off centered inferior to
      isocenter). Mean CT numbers (Hounsfield Units: HU) and noise (standard deviation
      of CT numbers: SD) were measured in the anterior (aHU, aSD) and posterior (pHU,
      pSD) abdominal wall subcutaneous fat and liver parenchyma (LivHU, LivSD) at the
      level of the porta hepatis. Patients' age, gender, weight, body mass index and
      maximal anteroposterior diameter were recorded. The data were analyzed using
      linear regression analysis. RESULTS: Most patients (81%; 320/395) were not
      correctly centered in the gantry isocenter for abdominal CT scanning. Mean CT
      numbers in the abdominal wall increased significantly with an increase in the off
      centering distance, regardless of the direction of the off-center (P < 0.05).
      There was a substantial increase in pSD (P = 0.01) and LivSD (P = 0.017) with off
      centering. Change in mean CT numbers and image noise along the off-center
      distance was influenced by the patient size (P < 0.01). CONCLUSION: Inappropriate
      patient centering for CT scanning adversely affects the reliability of mean CT
      numbers and image noise.

PMID- 22468192
TI  - Ablation margin assessment of liver tumors with intravenous contrast-enhanced C
      arm computed tomography.
AB  - AIM: To evaluate the feasibility of intravenous contrast-enhanced C-arm computed
      tomography (CT) for assessing ablative areas and margins of liver tumors.
      METHODS: Twelve patients (5 men, 7 women; mean age, 69.5 years) who had liver
      tumors (8 hepatocellular carcinomas, 4 metastatic liver tumors; mean size, 16.3
      mm; size range, 8-20 mm) and who underwent percutaneous radiofrequency ablations
      (RFAs) with a flat-detector C-arm system were retrospectively reviewed.
      Intravenously enhanced C-arm CT and multidetector computed tomography (MDCT)
      images were obtained at the end of the RFA sessions and 3-7 d after RFA to
      evaluate the ablative areas and margins. The ablated areas and margins were
      measured using axial plane images acquired by both imaging techniques, with prior
      contrast-enhanced MDCT images as the reference. The sensitivity, specificity, and
      positive and negative predictive values of C-arm CT for detecting insufficient
      ablative margins (< 5 mm) were calculated. Statistical differences in the
      ablative areas and margins evaluated with both imaging techniques were compared
      using a paired t-test. RESULTS: All RFA procedures were technically successful.
      Of 48 total ablative margins, 19 (39.6%) and 20 (41.6%) margins were found to be
      insufficient with C-arm CT and MDCT, respectively. Moreover, there were no
      significant differences between these 2 imaging techniques in the detection of
      these insufficient ablative margins. The sensitivity, specificity, and positive
      and negative predictive values for detecting insufficient margins by C-arm CT
      were 90.0%, 96.4%, 94.7% and 93.1%, respectively. The mean estimated ablative
      areas calculated from C-arm CT (462.5 +/- 202.1 mm(2)) and from MDCT (441.2 +/-
      212.5 mm(2)) were not significantly different. The mean ablative margins
      evaluated by C-arm CT (6.4 +/- 2.2 mm) and by MDCT (6.0 +/- 2.4 mm) were also not
      significantly different. CONCLUSION: The efficacy of intravenous contrast
      enhanced C-arm CT in assessing the ablative areas and margins after RFA of liver
      tumors is nearly equivalent to that of MDCT.

PMID- 22468193
TI  - Hepatic artery pseudoaneurysm after endoscopic biliary stenting for bile duct
      cancer.
AB  - We report a case of a pseudoaneurysm of the right hepatic artery observed 9 mo
      after the endoscopic placement of a Wallstent, for bile duct stenosis, which was
      treated with transcatheter arterial embolization. The patient presented with
      obstructive jaundice and was diagnosed with inoperable common bile duct cancer. A
      plastic stent was inserted endoscopically to drain the bile, and chemotherapy was
      initiated. Abdominal pain and jaundice appeared approximately 6 mo after the
      beginning of chemotherapy. A diagnosis of stent occlusion and cholangitis was
      made, and the plastic stent was removed and substituted with a self-expandable
      metallic stent (SEMS) endoscopically. Nine months after SEMS insertion, contrast
      enhanced computed tomography showed a pseudoaneurysm of the right hepatic artery
      protruding into the common bile duct lumen and in contact with the SEMS. The
      shape and size of the pseudoaneurysm and diameter of its neck was determined by
      contrast-enhanced ultrasonography using Sonazoid. A micro-catheter was led into
      the pseudoaneurysm in the right hepatic artery, GDCTM Detachable Coils were
      placed, and IDCTM Detachable Coils were then placed in the right hepatic artery
      on the distal and proximal sides of the pseudoaneurysm using the isolation
      method. There have been a few reports on pseudoaneurysm associated with stent
      placement in the biliary tract employing percutaneous transhepatic procedures,
      however, reports of pseudoaneurysms associated with endoscopic SEMS placement are
      very rare.

PMID- 22468194
TI  - Balloon-occluded retrograde transvenous obliteration for gastric varices via the
      intercostal vein.
AB  - Gastric varices are usually associated with a gastro-renal (G-R) shunt. However,
      the gastric varices described in this case report were not associated with a G-R
      shunt. The inflow vessel was the posterior gastric vein and the outflow vessels
      were the narrow inferior phrenic vein and the dilated cardio-phrenic vein. First,
      percutaneous transhepatic obliteration of the posterior gastric vein was
      performed, but the gastric varices remained patent. Then, micro-balloon
      catheterization of the subphrenic vein was carried out via the jugular vein,
      pericardial vein and cardio-phrenic vein, however, micro-balloon-occluded
      inferior phrenic venography followed by micro-coil embolization of the cardio
      phrenic vein revealed no delineation of gastric varices resulting in no further
      treatment. Thereafter, as a gastro-subphrenic-intercostal vein shunt developed, a
      micro-balloon catheter was advanced to the gastric varices via the intercostal
      vein and balloon-occluded retrograde transvenous obliteration (BRTO) was
      performed resulting in the eradication of gastric varices. BRTO for gastric
      varices via the intercostal vein has not previously been documented.

PMID- 22468195
TI  - Characteristics of nasal resonance and perceptual rating in prelingual hearing
      impaired adults.
AB  - OBJECTIVES: Resonance problems in hearing impaired (HI) individuals have been
      described as aspects of nasality. However, there are limitations in being able to
      explain the range of resonance problems. Therefore, this study suggests a
      perceptual rating that will effectively explain the characteristics of resonance
      problems in HI individuals. METHODS: Nasalance scores were obtained from 32
      subjects in each of HI and normal hearing (NH) groups using a nasometer. The
      subjects were categorized into groups based on normal and abnormal nasalance
      ranges. The abnormal nasalance range group was further divided into hyper-, hypo
      , and mixed-nasal groups. Nasalance scores were based the individuals performance
      in a series of passage and syllable tasks. The perceptual rating was evaluated
      using a newly introduced tool, 'vertical focus of resonance' (VFR), which focuses
      on the resonance energy in the frontal, throat, pharyngeal and nasal locations.
      RESULTS: The NH group demonstrated a significantly lower nasalance score in the
      oral coupling and passage tasks than the HI group. Based on the results of
      nasalance correlation analysis, the HI group showed highly significant
      correlations between syllable and passage tasks, as contrasted with the NH group.
      There were significant differences in VFR between the nasalance types in both the
      NH and the HI groups. CONCLUSION: The HI hyper-nasal group showed tendencies of
      velopharyngeal opening, as opposed to the HI hypo-nasal group which showed
      tendencies of velopharyngeal closure. The HI mixed-nasal group showed
      inappropriate coordination of velopharyngeal function. In the HI group, the
      results of VFR showed that the air flow and the resonance energy were not
      released from the cavity of resonance. The suggested VFR tool explains the
      focusing characteristics of resonance energy within a continuation of speech
      sound regardless of the phonetic environment. Therefore, VFR may be a useful tool
      in explaining the deviant resonance patterns of HI individuals.

PMID- 22468196
TI  - Reliability and validity of the chinese (mandarin) tinnitus handicap inventory.
AB  - OBJECTIVES: The Tinnitus Handicap Inventory (THI) is a commonly used self
      reporting tinnitus questionnaire. We undertook this study to determine the
      reliability and validity of the Chinese-Mandarin version of the Tinnitus Handicap
      Inventory (THI-CM) for measuring tinnitus-related handicaps. METHODS: We tested
      the test-retest reliability, internal reliability, and construct validity of the
      THI-CM. Two-hundred patients seeking treatment for primary or secondary tinnitus
      in Southwest China were asked to complete THI-CM prior to clinical evaluation.
      Patients were evaluated by a clinician using standard methods, and 40 patients
      were asked to complete THI-CM a second time 14+/-3 days after the initial
      interview. RESULTS: The test-retest reliability of THI-CM was high (Pearson
      correlation, 0.98), as was the internal reliability (Cronbach's alpha, 0.93).
      Factor analysis indicated that THI-CM has a unifactorial structure. CONCLUSION:
      The THI-CM version is reliable. The total score in THI-CM can be used to measure
      tinnitus-related handicaps in Mandarin-speaking populations.

PMID- 22468197
TI  - Rate of isolation and trends of antimicrobial resistance of multidrug resistant
      pseudomonas aeruginosa from otorrhea in chronic suppurative otitis media.
AB  - OBJECTIVES: To assess the rate of isolation of Pseudomonas aeruginosa (PA) and
      multidrug-resistant PA (MDR-PA) from patients with chronic suppurative otitis
      media (CSOM) otorrhea and the annual trend of antibiotic-resistance. METHODS:
      Otorrhea samples were collected aseptically from 1,598 CSOM patients. The rate of
      bacterial isolation and the results of antibiotic susceptibility testing were
      evaluated retrospectively. RESULTS: The PA isolation rate from CSOM otorrhea was
      24.4%. Of the 398 isolated strains tested for their susceptibilities to 10
      antibiotics, 395 strains showed definitive results. Of these, 183 (46.3%) were
      susceptible to whole antibiotics and 212 (53.7%) was resistant to more than 1
      antibiotics, with the frequency of antibiotics-resistance increasing
      significantly over time. Although strains susceptible to all antibiotics
      decreased over time, the rate of isolation of MDR-PA did not change
      significantly. Resistance to aminoglycosides and quinolones was higher than to
      other antibiotics and significantly increased over time, whereas resistance to
      other antibiotics showed no trend. CONCLUSION: MDR-PA, assessed using five
      individual antibiotics and six antibiotic-classes, showed no tendency to increase
      or decrease over time. This may have been due to increased concern about
      antibiotic-resistant bacterial strains, leading to improved infection control
      within hospitals and healthcare centers.

PMID- 22468198
TI  - Mastoid obliteration with silicone blocks after canal wall down mastoidectomy.
AB  - OBJECTIVES: To evaluate the usefulness of silicone blocks as graft material for
      mastoid cavity obliteration in the prevention of problematic mastoid cavities
      after canal wall down mastoidectomies. METHODS: Retrospective evaluation of 20
      patients who underwent mastoid obliteration with silicone blocks between 2002 and
      2009 at the Chonnam National University Hospital. The cases consisted of 17
      patients with chronic otitis media with cholesteatoma and 3 patients with
      adhesive otitis media. The postoperative follow-up period was an average 49
      months (range, 6 to 90 months). The surgical technique used at our institution
      composed four major steps: First, the canal wall down mastoidectomy was performed
      and the middle ear procedure was completed. The silicone blocks were used to fill
      up the mastoidectomized cavity. Then, a cortical bone pate was used to cover the
      surface of the silicone blocks. Finally, temporalis fascia and a split
      musculoperiosteal flap were used to surround the bone pate for reinforcement of
      the reconstructed canal wall. We examined postoperative success rate and hearing
      outcomes. RESULTS: In 19 cases (95%), the reconstructed canal wall maintained a
      cylindrical shape and the ear drum healed without perforation. In only 1 case
      (5%), the reconstructed canal wall was destroyed with ear drum perforation. The
      mean improvement in air-bone gap was about 12 dB (P<0.05), and the mean
      improvement in air-conduction was about 16 dB (P<0.05). CONCLUSION: We suggest
      that silicone blocks could be valuable resources as graft materials for mastoid
      obliteration after canal wall down mastoidectomies.

PMID- 22468199
TI  - Open-Label Observational Study for Evaluating the Short-term Benefits of
      Rabeprazole Medication on Laryngopharyngeal Reflux.
AB  - OBJECTIVES: The aims of this study were to determine the benefits of short-term
      empirical proton pump inhibitor (PPI) medication on laryngopharyngeal reflux
      (LPR) and to determine whether scores on the reflux symptom index (RSI) and the
      reflux finding score (RFS) could be combined to identify subgroups of patients
      that will more likely to improve with this medication. METHODS: Fifty-one Korean
      Otolaryngology Board-certified specialists joined this prospective, multi-center,
      and open-label observational study. A total of 1,142 adult patients with LPR was
      enrolled for 12 weeks of rabeprazol medication. According to pre-treatment scores
      on RSI and RFS, patients were divided into 4 subgroups. RFS and RSI were measured
      repeatedly with a month interval along the treatment period. Changes of RSI and
      RFS were analyzed in an overall study cohort as well as in each subgroup.
      RESULTS: Approximately 40% (n=455) of enrolled patients were followed up until 12
      weeks of PPI treatment. Significant improvement in RSI was obtained in 29%, 58%,
      and 75% of patients after 4, 8, and 12 weeks of PPI medication. RFS was improved
      in 16%, 42%, and 57% of the patients with 4, 8, and 12 weeks of PPI medication.
      All subgroups showed improvement regardless of their pre-treatment scores on the
      RSI and RFS. CONCLUSION: Even though RSI and RFS may be used as a general
      guideline for LPR management, pre-treatment RSI and RFS are not useful in
      predicting the patients' response to short-term PPI medication in the usual
      pattern of practice for LPR, which is mostly based on the physical evaluation and
      history taking.

PMID- 22468200
TI  - Long-term Study of Sialodochoplasty for Preventing Submandibular Sialolithiasis
      Recurrence.
AB  - OBJECTIVES: The transoral removal of stones by sialodochoplasty has been
      popularized in the treatment of submandibular sialolithiasis. However, the
      effectiveness of sialodochoplasty is controversial, and there are no reports on
      the long-term outcomes of this procedure. The purpose of this study was to assess
      the effectiveness and long-term outcomes of sialodochoplasty in patients with
      submandibular sialolithiasis. METHODS: We conducted a cross-sectional study that
      included retrospective chart reviews and prospective telephone or interview
      surveys of 150 patients treated for submandibular sialolithiasis from March 2001
      to January 2008. The patients were treated with two different procedures by two
      different surgeons. One surgeon performed a transoral sialolithectomy without
      sialodochoplasty in 107 patients (SS group), and the other surgeon performed a
      transoral sialolithectomy with sialodochoplasty in 43 patients (SP group).
      RESULTS: The success rate of transoral sialolithectomy was 98.1% in the SS group
      and 93% in the SP group. The recurrence rates of symptoms or stones were 1.9% and
      4.7% in the SS and SP groups, respectively. The incidence of postoperative
      transient hypoesthesia was 13.1% in the SS group and 34.9% in the SP group. The
      mean operating times were 29.79 and 47.44 minutes in the SS and SP groups,
      respectively. The mean percentage of general anesthesia was 42.1% in the SS group
      and 83.7% in the SP group. CONCLUSION: Sialodochoplasty in addition to transoral
      sialolithectomy for submandibular sialolithiasis did not affect the rate of
      symptom or stone recurrence, but did increase the postoperative hypoesthesia
      incidence and general anesthesia percentage.

PMID- 22468201
TI  - A Prospective Population-based Study of Total Nasal Resistance in Korean
      Subjects.
AB  - OBJECTIVES: Rhinomanometry is a widely accepted method for objective assessment
      of nasal patency. However, few studies have reported the values of otherwise
      healthy population for nasal resistance in East Asians. The purpose of this study
      was to measure normal total nasal resistance (TNR) values in a large sample of
      Korean adults and to reveal parameters contributing to TNR values. METHODS:
      Subjects were enrolled from a cohort of the Korean Genome and Epidemiology Study.
      They were evaluated by anthropometry, questionnaire, and active anterior
      rhinomanometry at transnasal pressures of 100 and 150 Pascal (Pa). RESULTS: The
      study sample consisted of 2,538 healthy subjects (1,298 women and 1,240 men) aged
      20 to 80 years. Normal reference TNR values were 0.19+/-0.08 Pa/cm(3)/second at
      100 Pa and 0.22+/-0.09 Pa/cm(3)/second at 150 Pa. The TNR of women was
      significantly higher than that of men (P<0.0001). TNR decreased with increasing
      age in both genders (P<0.05). In women, lower body weight was related to
      increasing TNR. In men, current smokers had higher TNR than ex-smokers and never
      smokers. CONCLUSION: The results of the present study provide information
      regarding the values of otherwise healthy population of TNR and parameters
      associated with TNR in Korean adults.

PMID- 22468202
TI  - Palatal myoclonus associated with orofacial buccal dystonia.
AB  - Palatal myoclonus is a rare condition in which there are rhythmic jerky movements
      of the soft palate and sometimes of the other muscles innervated by the brainstem
      A particularly annoying symptom is a rhythmic clicking sound in the ear due to
      the opening and closing of the Eustachian tube. Orofacial buccal dystonia is a
      focal dystonia with sustained spasms of the masticatory, facial or lingual
      muscles. The frequent symptoms of this disease have mainly been reported to be
      involuntary and possibly painful jaw opening, closing, deflecting and retruding,
      or a combination of the above. However, the subtle and unnoticeable involuntary
      movement of multiple facial muscles, which might be an infrequent symptom of
      orofacial buccal dystonia, makes this disease hard to diagnose. Understanding the
      functional orofacial anatomy that is responsible for the clinical signs and
      symptoms is necessary for making a proper diagnosis. Here we report on a rare
      case of palatal myoclonus that was associated with orofacial buccal dystonia, and
      such a case has not been previously reported. We describe the diagnostic approach
      and excellent treatment results after Botulinum toxin A (Dysport) injection and
      proper counseling.

PMID- 22468203
TI  - Giant cell tumor of the mandible.
AB  - A 53-year-old woman presented with left mandibular area pain, trismus, and facial
      numbness that had persisted for 4 years. Physical examination revealed a 3*5 cm,
      hard, non-tender, and round mass on the left mandibular area. Computed tomography
      and magnetic resonance imaging revealed an expansile tumor involving the left
      mandibular ramus and temporomandibular joint area with bone destruction,
      extending to the base of middle cranial fossa and left zygomatic bone. The mass
      at the segment of left mandible and zygomatic bone, and base of middle cranial
      fossa was removed. Pathological examination of the mass revealed a giant cell
      tumor. The defect was reconstructed with iliac bone for the mandible and temporal
      bone and fascia for the cranial bone and dura. The case is described along with a
      review of the literature.

PMID- 22468204
TI  - One-stage reconstruction for midfacial defect after radical tumor resection.
AB  - A serious midface defect involving resection of squamous cell carcinoma
      originating from the hard palate was treated by an unusual reconstructive
      strategy. After tumor resection, surgical reconstruction was accomplished in one
      stage using one free flap with one distant and local flap: a radial forearm flap
      to reconstruct the upper lip, a forehead flap to reconstruct the external nose, a
      cantilever calvarial bone graft to replace the nasal skeleton and a nasolabial
      flap and split thickness skin graft to cover the internal nasal lining. The
      rationale for this one-stage reconstruction and the problems associated with
      midfacial reconstruction after wide tumor excision are discussed.

PMID- 22468205
TI  - 3D Segmentation of Prostate Ultrasound images Using Wavelet Transform.
AB  - The current definitive diagnosis of prostate cancer is transrectal ultrasound
      (TRUS) guided biopsy. However, the current procedure is limited by using 2D
      biopsy tools to target 3D biopsy locations. This paper presents a new method for
      automatic segmentation of the prostate in three-dimensional transrectal
      ultrasound images, by extracting texture features and by statistically matching
      geometrical shape of the prostate. A set of Wavelet-based support vector machines
      (W-SVMs) are located and trained at different regions of the prostate surface.
      The WSVMs capture texture priors of ultrasound images for classification of the
      prostate and non-prostate tissues in different zones around the prostate
      boundary. In the segmentation procedure, these W-SVMs are trained in three
      sagittal, coronal, and transverse planes. The pre-trained W-SVMs are employed to
      tentatively label each voxel around the surface of the model as a prostate or non
      prostate voxel by the texture matching. The labeled voxels in three planes after
      post-processing is overlaid on a prostate probability model. The probability
      prostate model is created using 10 segmented prostate data. Consequently, each
      voxel has four labels: sagittal, coronal, and transverse planes and one
      probability label. By defining a weight function for each labeling in each
      region, each voxel is labeled as a prostate or non-prostate voxel. Experimental
      results by using real patient data show the good performance of the proposed
      model in segmenting the prostate from ultrasound images.

PMID- 22468206
TI  - Nonrigid Registration and Classification of the Kidneys in 3D Dynamic Contrast
      Enhanced (DCE) MR Images.
AB  - We have applied image analysis methods in the assessment of human kidney
      perfusion based on 3D dynamic contrast-enhanced (DCE) MRI data. This approach
      consists of 3D non-rigid image registration of the kidneys and fuzzy C-mean
      classification of kidney tissues. The proposed registration method reduced motion
      artifacts in the dynamic images and improved the analysis of kidney compartments
      (cortex, medulla, and cavities). The dynamic intensity curves show the successive
      transition of the contrast agent through kidney compartments. The proposed method
      for motion correction and kidney compartment classification may be used to
      improve the validity and usefulness of further model-based pharmacokinetic
      analysis of kidney function.

PMID- 22468208
TI  - Clinical significance of free-to-total prostate-specific antigen (PSA) ratio in
      advanced prostate cancer patients with PSA less than 0.1 ng/ml after hormone
      treatment.
AB  - PURPOSE: We analyzed the pattern of change in the free-to-total prostate-specific
      antigen (f/t PSA) ratio and the progression to castration-resistant prostate
      cancer (CRPC) in patients with advanced prostate cancer who received hormone
      treatment and whose PSA nadir was below 0.1 ng/ml. MATERIALS AND METHODS: We
      retrospectively analyzed the medical records of 52 patients with advanced
      prostate cancer. All patients were treated with maximum androgen blockade
      (gonadotrophin-releasing hormone agonist and anti-androgen agents). The patients
      were divided into two groups: those with a nadir f/t PSA ratio above 60% and
      those with a nadir f/t PSA ratio of 60% or below. Age, initial PSA, clinical
      stage, lymph node metastasis, bone metastasis, and follow-up data, including PSA,
      free PSA, and f/t PSA ratio, were collected. The Mann-Whitney U-test, Fisher
      exact test, chi-square test, Kaplan-Meier survival analysis, and log rank test
      were used. RESULTS: There were 24 patients in the group with a nadir f/t PSA
      ratio above 60% and 28 patients in the group with a nadir f/t PSA ratio of 60% or
      below. After hormone therapy, the median f/t PSA ratio in each group increased
      from 37% and 34% at 3 months to 75% and 60% at 6 months, respectively. At 9
      months, however, the f/t PSA ratio increased to 80% in the group with a nadir f/t
      PSA ratio above 60%, whereas it decreased to 31% in the group with a nadir f/t
      PSA ratio of 60% or below. From 9 to 15 months, the f/t PSA ratio showed a
      tendency to decrease (75 to 37% and 27 to 20%, respectively). The progression to
      CRPC was significantly different between the two groups (10 vs. 24). CONCLUSIONS:
      Progression to CRPC was significantly higher in the group with a lower f/t PSA
      ratio. Additionally, the pattern of change in the f/t PSA ratio was significantly
      different after 9 months. Collectively, the f/t PSA ratio can be used as an
      additional marker for prognosis of hormone treatment.

PMID- 22468207
TI  - Benign prostatic hyperplasia: from bench to clinic.
AB  - Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men,
      and often results in lower urinary tract symptoms (LUTS). This chronic disease
      has important care implications and financial risks to the health care system.
      LUTS are caused not only by mechanical prostatic obstruction but also by the
      dynamic component of obstruction. The exact etiology of BPH and its consequences,
      benign prostatic enlargement and benign prostatic obstruction, are not
      identified. Various theories concerning the causes of benign prostate enlargement
      and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen
      receptor, epithelial-stromal interaction, and lifestyle, are discussed.
      Incomplete overlap of prostatic enlargement with symptoms and obstruction
      encourages focus on symptoms rather than prostate enlargement and the shifting
      from surgery to medicine as the treatment of BPH. Several alpha antagonists,
      including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent
      efficacy without severe adverse effects. In addition, new alpha antagonists,
      silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH
      treatments. In surgical treatment, laser surgery such as photoselective
      vaporization of the prostate and holmium laser prostatectomy have been introduced
      to reduce complications and are used as alternatives to transurethral resection
      of the prostate (TURP) and open prostatectomy. The status of TURP as the gold
      standard treatment of BPH is still evolving. We review several preclinical and
      clinical studies about the etiology of BPH and treatment options.

PMID- 22468209
TI  - Effects of partial nephrectomy on postoperative blood pressure.
AB  - PURPOSE: The effects of partial nephrectomy (PN) on postoperative blood pressure
      (BP) are not known, and PN has the potential to worsen BP. We therefore sought to
      determine whether PN alters postoperative BP. MATERIALS AND METHODS: Patients who
      underwent PN for suspected malignancy at our institution from 2002 to 2008 were
      included. Data on BP and medication from before and after PN were retrieved from
      family physicians. BP and number of antihypertensive medications were compared
      after surgery with preoperative values by use of paired t tests and Chi-squared
      analyses, respectively. RESULTS: Of 74 patients undergoing PN and providing
      consent, 48 met the inclusion and exclusion criteria, with a median follow-up of
      24 months. For the early postoperative period (1 month to 1 year after surgery),
      the mean BPs (132.3/77.0 mmHg) were unchanged compared with preoperative values
      (132.4/78.0 mmHg; p=0.59 systolic BP and p=0.30 diastolic BP). For the later
      postoperative period (beyond 1 year after surgery), the mean postoperative
      systolic BP was unchanged from the mean preoperative systolic BP (131.2 mmHg vs.
      132.4 mmHg, respectively; p>0.30). However, the corresponding average diastolic
      BP was lower in the long term (78.0 mmHg versus 76.4 mmHg respectively; p=0.01).
      No significant difference in the mean number of BP medications prescribed
      preoperatively, at one year, and beyond one year was identified (p>0.37).
      CONCLUSIONS: PN does not result in initial or long-term postoperative
      deterioration in BP.

PMID- 22468210
TI  - Characterization of small renal masses less than 4 cm with quadriphasic
      multidetector helical computed tomography: differentiation of benign and
      malignant lesions.
AB  - PURPOSE: To identify the characteristic quadriphasic (unenhanced,
      corticomedullary, nephrographic, and excretory phase) helical multidetector
      computed tomography (MDCT) features of renal masses less than 4 cm to distinguish
      benign from malignant renal masses. MATERIALS AND METHODS: In total, 84 patients
      were retrospectively analyzed to determine the characteristic features for the
      prediction of subtypes of small renal masses. The patients' age, gender, and
      tumor size and CT features, including the presence of intra-tumor degenerative
      changes, septation, calcification, and wall irregularity, were evaluated. In
      addition, the degree and pattern of enhancement obtained during four phases were
      analyzed. The relationship between the subtype of the small renal masses and the
      gender, morphological features, and pattern of contrast enhancement on the CT was
      analyzed by using the chi-square test. Tumor size and degree of contrast
      enhancement were compared by the Mann-Whitney U test. The predictive value of
      each of the CT features was determined by multivariate logistic regression
      analysis. RESULTS: Of the 84 small renal masses, 17 (20%) were benign and 67
      (80%) were malignant. Univariate analysis revealed that renal cell carcinoma
      lesions showed heterogeneous enhancement (p=0.002) and higher mean attenuation
      value on the corticomedullary and nephrographic phases (135.1+/-53.9, p=0.000,
      and 132.4+/-43.6, p=0.006). The multivariate analysis with logistic regression
      model showed that only the mean attenuation value on the corticomedullary phase
      had a statistically significant correlation (p=0.021). CONCLUSIONS: For the
      characterization of small renal masses, the degree of enhancement on the
      corticomedullary phase is a valuable parameter. Furthermore, the heterogeneous
      enhancement pattern and degree of enhancement on the nephrographic phase can
      provide information for differentiating small renal masses.

PMID- 22468211
TI  - Laparoendoscopic single-site surgery for benign urologic disease with a homemade
      single port device: design and tips for beginners.
AB  - PURPOSE: A single surgeon skilled in conventional laparoscopic surgery used
      laparoendoscopic single-site surgery (LESS) to treat benign urological diseases.
      This study reports our surgical results and introduces a simple technique with
      tips based on our experience. MATERIALS AND METHODS: LESS surgery was performed
      on 116 patients by use of a homemade single-port device composed of an Alexis
      wound retractor and a powder-free surgical glove. Cases were 44 varicocelectomies
      (including 8 bilateral cases), 38 renal cyst marsupializations (including 3
      bilateral cases), 26 ureterolithotomies (with 1 concomitant ureterolithotomy and
      contralateral renal cyst marsupialization), 4 prostatic enucleations, and 4
      bladder rupture repairs. The mean patient age was 44.43+/-16.46 years (range, 11
      to 76 years), and the male-to-female ratio was 87:29. RESULTS: In one
      ureterolithotomy case, LESS was converted to conventional laparoscopic surgery.
      The mean operative time was 87.03+/-45.03 minutes, the estimated blood loss was
      61.90 ml (range, 0 to 2,000 ml), and the mean hospital stay was 3.03+/-2.12 days.
      Two patients underwent single-port transvesical enucleation of the prostate
      (STEP) requiring patient-controlled anesthesia. No patients developed major
      complications, and all patients were satisfied, with 75.86% expressing a high
      degree of satisfaction. CONCLUSIONS: We report successful treatment outcomes for
      LESS in 116 cases of benign urological disease. Our findings suggest that LESS
      can replace conventional laparoscopy.

PMID- 22468212
TI  - One-year outcomes of mid-urethral sling procedures for stress urinary
      incontinence according to body mass index.
AB  - PURPOSE: The purpose of our study was to investigate the safety and efficacy of
      the suprapubic arch (SPARC) sling operation and the transobturator tape (MONARC)
      sling operation according to body mass index (BMI). MATERIALS AND METHODS:
      Between January 1, 2004, and July 12, 2009, a retrospective clinical trial was
      performed with 284 patients treated by the SPARC sling procedure and 49 patients
      treated by the MONARC sling procedure. The women were classified into 3 groups by
      BMI according to the WHO Expert Consultation: normal weight (A, BMI 18.5 to 22.9
      kg/m2), overweight (B, BMI 23 to 27.5 kg/m2), and obese (C, BMI>27.6 kg/m2).
      Patients' characteristics and clinical outcomes of the operation were analyzed
      according to BMI at 1 year after surgery via questionnaires and interviews with
      the patients about their voiding symptoms and medical records. RESULTS: There
      were 103 patients in group A, 186 in group B, and 34 in group C. The objective
      cure rates for groups A, B, and C after the SPARC procedure were 94.4%, 96.7%,
      and 96.8%, respectively (p=0.321), and the subjective cure rates were 94.4%,
      96.1%, and 96.8%, respectively (p=0.222). The objective cure rates for groups A,
      B, and C after the MONARC procedure were 100.0%, 90.9%, and 66.7%, respectively
      (p=0.742), and the subjective cure rates were 92.3%, 93.9%, and 66.7%,
      respectively (p=0.779). The complication rates were similar among the three study
      groups. CONCLUSIONS: Mid-urethral sling procedures for urinary incontinence
      result in similar objective and subjective cure rates and postoperative
      complications irrespective of BMI.

PMID- 22468213
TI  - Efficacy and safety of tamsulosin for treating lower urinary tract symptoms
      associated with benign prostatic hyperplasia: a multicenter, randomized,
      controlled, open-label non-inferiority study.
AB  - PURPOSE: To compare the efficacy and safety of Sulosin D (PACIFICPHARMA, Korea)
      and Harnal D (ASTELLAS PHARMA KOREA, Korea) in treating patients with lower
      urinary tract symptoms associated with benign prostatic hyperplasia (BPH).
      MATERIALS AND METHODS: This randomized, controlled, open-label, multicenter non
      inferiority study was conducted at four sites in Korea. We randomly assigned 123
      patients with an International Prostate Symptom Score (IPSS) >=12 to receive
      either Sulosin D or Harnal D treatment for 8 weeks. The primary outcome was the
      mean change in IPSS from baseline to endpoint. Secondary outcomes were the mean
      change from baseline to endpoint in IPSS quality of life subscores, maximum
      uroflowmetry (Qmax), and post-voiding residuals (PVR). RESULTS: In all, 123
      patients were randomly assigned (60 Sulosin D and 63 Harnal D). The changes in
      the total IPSS from baseline in the Sulosin D- and Harnal D-treated groups were 
      4.97 and -4.03, respectively. There were significant decreases compared with
      baseline in both groups. The mean difference (Sulosin D - Harnal D) was -0.91
      (with a two-sided 90% confidence interval), inferring that Sulosin D was not
      inferior to Harnal D. The mean changes in the IPSS subscore, Qmax, and PVR from
      baseline were comparable between the groups (both p>0.05). During the treatment
      periods, the incidence of adverse events was 23.33% and 34.92% in the Sulosin D
      and Harnal D groups, respectively (p=0.1580). CONCLUSIONS: We demonstrate the non
      inferiority of Sulosin D to Harnal D in patients with lower urinary tract
      symptoms associated with BPH.

PMID- 22468214
TI  - Long-term clinical outcomes of the tension-free vaginal tape procedure for the
      treatment of stress urinary incontinence in elderly women over 65.
AB  - PURPOSE: The aim of this study was to assess the long-term clinical outcomes of
      the tension-free vaginal tape (TVT) procedure for stress urinary incontinence
      (SUI) in elderly women and to identify the factors influencing failure in these
      cases. MATERIALS AND METHODS: Women with SUI who underwent a TVT procedure were
      studied. "Cure" was defined as no urine leakage at all in any circumstances and
      "improvement" was defined as some urine leakage but a score of over 4 points out
      of 5 in a satisfaction inquiry. Patients were divided into two groups (middle
      aged, <65 years and elderly, >=65 years) for comparison of clinical outcomes. In
      the elderly group, patients were subdivided into two groups (cure and no cure
      groups) and were compared to identify the factors influencing failure. RESULTS: A
      total of 136 women (middle-aged group, 106; elderly group, 30) were enrolled in
      the study. The mean ages of the patients in the 2 groups were 53.5+/-5.9 and
      72.0+/-5.0 years and the mean follow-up times were 50.5+/-9.4 and 48.8+/-9.1
      months, respectively. The cure and improvement rates in the middle-aged and
      elderly groups were 80.2% vs. 66.7% and 4.7% vs. 3.3%, respectively (p>0.05). The
      satisfaction scores in the middle-aged and elderly groups were 3.8+/-1.1 vs.
      3.3+/-1.5 points (p>0.05). In the elderly group, the body mass index of the cure
      and no cure groups were 24.6+/-3.3 kg/m(2) and 26.6+/-1.0 kg/m2, and body mass
      index was the only factor that differed significantly between the two subgroups
      (p=0.028). CONCLUSIONS: Our long-term results suggest that TVT is an effective
      treatment even in elderly women. However, elderly women who are obese should be
      counseled carefully about the success rate.

PMID- 22468215
TI  - Correlation between lower urinary tract symptoms and premature ejaculation in
      Korean men older than 40 years old [corrected].
AB  - PURPOSE: To evaluate the correlation between lower urinary tract symptoms (LUTS)
      and premature ejaculation (PE) in Korean men older than 40 years. MATERIALS AND
      METHODS: In total, 258 men older than 40 years completed the International
      Prostate Symptom Score (IPSS; total score, storage symptoms [ST], and voiding
      symptoms [VD]), a 5-item version of the International Index of Erectile Function
      (IIEF-5), and the Premature Ejaculation Diagnostic Tool (PEDT). The study
      examined the relationship between LUTS and PE. In the PEDT, PE is defined as a
      score >=11. RESULTS: The prevalence of PE was 29.1% with the PEDT versus a self
      reported value of 49.5%. The prevalence of PE was 30.9% in 40 to 59-year-old men
      (21.3%) and 28.1% in 60 to 79 year-old men (78.7%). In men 40 to 59 and 60 to 79
      years old, the mean PEDT, IPSS, and IIEF-5 scores were 8.65 and 7.88, 13.5 and
      12.38, and 15.83 and 13.69, respectively. No significant correlations were
      observed between the total and subscale scores of the IPSS (p=0.204) and the PEDT
      (p=0.309) with increasing age, whereas a significant negative correlation was
      detected between the IIEF-5 and age (p=0.002). The PEDT score was significantly
      correlated with the IPSS-ST (r=0.326, p<0.001), IPSS-VD (r=0.183, p=0.005), IPSS
      total (r=0.310, p<0.001), and IIEF-5 total (r=-0.248, p<0.001). CONCLUSIONS:
      LUTS, especially storage symptoms, were related to PE. In elderly men, control of
      both erectile dysfunction and LUTS may play an important role in managing PE.

PMID- 22468216
TI  - Efficacy of hydrodistention implantation technique in treating high-grade
      vesicoureteral reflux.
AB  - PURPOSE: In the endoscopic treatment of vesicoureteral reflux, the relatively
      high rate of success, the simplicity of the procedure, high patient compliance,
      and a lack of complications has led to the increased development of injection
      materials and techniques. We report a method of identifying and maintaining a
      clear visual field during ureteral and bladder submucosal wall injection of a
      dextranomer/hyaluronic acid copolymer (Deflux, Oceana, Therapeutics Inc.) by use
      of the hydrodistention implantation technique (HIT) with the aid of temporary
      ureteral catheter insertion. MATERIALS AND METHODS: We prospectively reviewed
      patients with grade IV or V reflux who received an endoscopic injection of
      Deflux. Reflux grade was evaluated before and after treatment (3 months) by use
      of voiding cystourethrograms. Conventional sub-trigonal injection (STING) was
      performed with injection of Deflux underneath the bladder mucosa at the 6 o'clock
      position. HIT was performed either with hydrodistention or with guidewire
      insertion. These techniques increase visualization of the intramural portion of
      the distal ureteral wall. Patients with treatment failures were offered
      reinjection up to three times. RESULTS: Sixty-three patients completed endoscopic
      injection and follow-up of 3 months. The overall resolution rate for conventional
      STING was 58%, i.e., 67% for grade IV and 43% for grade V. The overall resolution
      rate for HIT was 80%, i.e., 93% for grade IV and 66% for grade V. The modified
      methods showed higher resolution rates for overall cure owing to the success in
      patients with grade IV reflux (p=0.026). Although the success of grade V
      treatment was higher with the modified method, the success rate was not
      statistically significant (p=0.27). CONCLUSIONS: HIT with the use of either
      hydrodistention or a guidewire to aid in visualization of the intramural portion
      of the distal ureter is an effective treatment for high-grade vesico-ureteral
      reflux.

PMID- 22468217
TI  - DNA methylation of GSTP1 in human prostate tissues: pyrosequencing analysis.
AB  - PURPOSE: DNA methylation is an important epigenetic mechanism of gene regulation
      and plays essential roles in tumor initiation and progression. Differences in
      methylation patterns between neoplastic and normal cells can be used to detect
      the presence of cancer. The aim of the present study was to evaluate the
      usefulness of glutathione-S-transferase-Pi (GSTP1) hypermethylation in
      discriminating between normal and prostate cancer (PCa) cells and in predicting
      tumor characteristics by use of quantitative pyrosequencing analysis. MATERIALS
      AND METHODS: A total of 100 human prostate tissues obtained from our institute
      were used in this study: 45 for benign prostatic hyperplasia (BPH) and 55 for
      PCa. The methylation level of GSTP1 was examined by a quantitative pyrosequencing
      analysis. The associations between GSTP1 methylation level and clinico
      pathological parameter were also compared. RESULTS: The level of GSTP1
      methylation was significantly higher in PCa samples than in BPH samples (56.7+/
      32.7% vs. 1.6+/-2.2%, p<0.001). The sensitivity and specificity of GSTP1
      methylation status in discriminating between PCa and BPH reached 85.5% and 100%,
      respectively. Even after stratification by stage, Gleason score, and prostate
      specific antigen (PSA) level, similar results were obtained. A positive
      correlation between GSTP1 methylation level and serum PSA level was observed
      (r=0.303, p=0.002). There were no associations between GSTP1 methylation level
      and age, Gleason score, and staging. CONCLUSIONS: Our study demonstrates that
      GSTP1 methylation is associated with the presence of PCa and PSA levels. This
      methylation marker is a potentially useful indicator for the detection and
      monitoring of PCa.

PMID- 22468218
TI  - Primary malignant melanoma of the female urethra.
AB  - We report here on a rare case of primary malignant melanoma of the female
      urethra. A 69-year-old female presented at our hospital with a several month
      history of dysuria, poor stream, gross hematuria, intermittent blood spots, and a
      painful mass at the external urethral meatus. The physical examination revealed a
      soft, small, chestnut-sized lesion through the urethral orifice. The mass was tan
      colored, ulcerated, covered with necrotic tissue, and protruded from the external
      urethral meatus. The mass was removed by wide local excision under spinal
      anesthesia. The pathological diagnosis was malignant melanoma of the urethra.
      Computed tomography of the abdomen as well as a whole-body bone scan showed no
      evidence of metastasis. The patient has been free of disease for 6 months
      postoperatively. We discuss the clinicopathologic features and treatment of this
      tumor.

PMID- 22468219
TI  - Giant multilocular cystadenoma of the prostate: a rare cause of huge cystic
      pelvic mass.
AB  - Giant multilocular prostatic cystadenoma is a rare benign tumor that evolves from
      the prostate gland. Obstructive voiding symptoms occur in all reported cases.
      These lesions do not invade adjacent structures. Preoperative radiologic
      evaluation can define the benign nature of the lesion. Here we report a case of
      large cystic lesions identified by magnetic resonance imaging and sonographic
      findings that caused an extensive mass effect in the pelvis. When retrovesical,
      huge cystic lesions fill the pelvis completely in young men, with high levels of
      serum prostate-specific antigen, giant multilocular prostatic cystadenoma should
      be considered as a differential diagnosis. To our knowledge, this is the youngest
      case of prostatic cystadenoma reported in the literature.

PMID- 22468220
TI  - The importance of the vaginal delivery route for antiretrovirals in HIV
      prevention.
AB  - The HIV/AIDS pandemic continues to be a global health priority, with high rates
      of new HIV-I infections persisting in young women. One HIV prevention strategy is
      topical pre-exposure prophylactics or microbicides, which are applied vaginally
      or rectally to protect the user from HIV and possibly other sexually transmitted
      infections. Vaginal microbicide delivery will be the focus of this review.
      Multiple nonspecific and specific antiretroviral microbicide products have been
      clinically evaluated, and many are in preclinical development, The events of HIV
      mucosal transmission and dynamics of the cervicovaginal environment should be
      considered for successful vaginal microbicide delivery. Beyond conventional
      vaginal formulations, intravaginal rings, tablets and films are employed as
      platforms in the hope to increase the likelihood of microbicide use. Furthermore,
      combining multiple antiretrovirals within a given formulation, combining a
      microbicide product with a vaginal device and integrating novel drug-delivery
      strategies within a microbicide product are approaches to successful vaginal
      microbicide delivery.

PMID- 22468223
TI  - Consensus clustering in complex networks.
AB  - The community structure of complex networks reveals both their organization and
      hidden relationships among their constituents. Most community detection methods
      currently available are not deterministic, and their results typically depend on
      the specific random seeds, initial conditions and tie-break rules adopted for
      their execution. Consensus clustering is used in data analysis to generate stable
      results out of a set of partitions delivered by stochastic methods. Here we show
      that consensus clustering can be combined with any existing method in a self
      consistent way, enhancing considerably both the stability and the accuracy of the
      resulting partitions. This framework is also particularly suitable to monitor the
      evolution of community structure in temporal networks. An application of
      consensus clustering to a large citation network of physics papers demonstrates
      its capability to keep track of the birth, death and diversification of topics.

PMID- 22468224
TI  - Origin of the relatively low transport mobility of graphene grown through
      chemical vapor deposition.
AB  - The reasons for the relatively low transport mobility of graphene grown through
      chemical vapor deposition (CVD-G), which include point defect, surface
      contamination, and line defect, were analyzed in the current study. A series of
      control experiments demonstrated that the determinant factor for the low
      transport mobility of CVD-G did not arise from point defects or surface
      contaminations, but stemmed from line defects induced by grain boundaries.
      Electron microscopies characterized the presence of grain boundaries and
      indicated the polycrystalline nature of the CVD-G. Field-effect transistors based
      on CVD-G without the grain boundary obtained a transport mobility comparative to
      that of Kish graphene, which directly indicated the detrimental effect of grain
      boundaries. The effect of grain boundary on transport mobility was qualitatively
      explained using a potential barrier model. Furthermore, the conduction mechanism
      of CVD-G was also investigated using the temperature dependence measurements.
      This study can help understand the intrinsic transport features of CVD-G.

PMID- 22468222
TI  - miRNA-mediated immune regulation and immunotherapeutic potential in glioblastoma.
AB  - Glioblastoma (GB), the most common primary neoplasm of the CNS, remains
      universally fatal with standard therapies and has a mean overall survival time of
      only 14.6 months. Even in the most favorable situations most patients do not
      survive longer than 2 years. Another hallmark of GBs, apart from the poor control
      of proliferation, is an immune suppressed tumor microenvironment. miRNAs usually
      bind the 3' untranslated region of target mRNAs and direct their post
      transcriptional repression. Certain miRNAs are known to have altered expression
      levels in GB tumors, and in many immune cell subtypes. miRNAs have been found to
      serve important roles in gene regulation and are implicated in many processes in
      oncogenesis and immune deregulation. In this article we focus on the miRNAs
      involved in gliomagenesis and in the regulation of the immune response. We also
      present current challenges and miRNA immunotherapeutic strategies that should be
      investigated further.

PMID- 22468221
TI  - Targeting blood-brain barrier changes during inflammatory pain: an opportunity
      for optimizing CNS drug delivery.
AB  - The blood-brain barrier (BBB) is the most significant obstacle to effective CNS
      drug delivery. It possesses structural and biochemical features (i.e., tight
      junction protein complexes and, influx and efflux transporters) that restrict
      xenobiotic permeation. Pathophysiological stressors (i.e., peripheral
      inflammatory pain) can alter BBB tight junctions and transporters, which leads to
      drug-permeation changes. This is especially critical for opioids, which require
      precise CNS concentrations to be safe and effective analgesics. Recent studies
      have identified molecular targets (i.e., endogenous transporters and
      intracellular signaling systems) that can be exploited for optimization of CNS
      drug delivery. This article summarizes current knowledge in this area and
      emphasizes those targets that present the greatest opportunity for controlling
      drug permeation and/or drug transport across the BBB in an effort to achieve
      optimal CNS opioid delivery.

PMID- 22468225
TI  - Metabolic engineering of the iodine content in Arabidopsis.
AB  - Plants are a poor source of iodine, an essential micronutrient for human health.
      Several attempts of iodine biofortification of crops have been carried out, but
      the scarce knowledge on the physiology of iodine in plants makes results often
      contradictory and not generalizable. In this work, we used a molecular approach
      to investigate how the ability of a plant to accumulate iodine can be influenced
      by different mechanisms. In particular, we demonstrated that the iodine content
      in Arabidopsis thaliana can be increased either by facilitating its uptake with
      the overexpression of the human sodium-iodide symporter (NIS) or through the
      reduction of its volatilization by knocking-out HOL-1, a halide
      methyltransferase. Our experiments show that the iodine content in plants results
      from a balance between intake and retention. A correct manipulation of this
      mechanism could improve iodine biofortification of crops and prevent the release
      of the ozone layer-threatening methyl iodide into the atmosphere.

PMID- 22468226
TI  - Strong superconducting proximity effect in pb-bi(2)te(3) hybrid structures.
AB  - To study the interface between a conventional superconductor and a topological
      insulator, we fabricated Pb-Bi(2)Te(3)-Pb lateral and sandwiched junctions, and
      performed electron transport measurements down to low temperatures. The results
      show that there is a strong superconducting proximity effect between Bi(2)Te(3)
      and Pb, as that a supercurrent can be established along the thickness direction
      of the Bi(2)Te(3) flakes (100~300 nm thick) at a temperature very close to the
      superconducting T(c) of Pb. Moreover, a Josephson current can be established over
      several microns in the lateral direction between two Pb electrodes on the
      Bi(2)Te(3 )surface. We have further demonstrated that superconducting quantum
      interference devices can be constructed based on the proximity-effect-induced
      superconductivity. The critical current of the devices exhibits s-wave-like
      interference and Fraunhofer diffraction patterns. With improved designs,
      Josephson devices of this type would provide a test-bed for exploring novel
      phenomena such as Majorana fermions in the future.

PMID- 22468227
TI  - Broadband metamaterial for nonresonant matching of acoustic waves.
AB  - Unity transmittance at an interface between bulk media is quite common for
      polarized electromagnetic waves incident at the Brewster angle, but it is rarely
      observed for sound waves at any angle of incidence. In the following, we
      theoretically and experimentally demonstrate an acoustic metamaterial possessing
      a Brewster-like angle that is completely transparent to sound waves over an ultra
      broadband frequency range with >100% bandwidth. The metamaterial, consisting of a
      hard metal with subwavelength apertures, provides a surface impedance matching
      mechanism that can be arbitrarily tailored to specific media. The nonresonant
      nature of the impedance matching effectively decouples the front and back
      surfaces of the metamaterial allowing one to independently tailor the acoustic
      impedance at each interface. On the contrary, traditional methods for acoustic
      impedance matching, for example in medical imaging, rely on resonant tunneling
      through a thin antireflection layer, which is inherently narrowband and angle
      specific.

PMID- 22468228
TI  - Sustainable institutionalized punishment requires elimination of second-order
      free-riders.
AB  - Although empirical and theoretical studies affirm that punishment can elevate
      collaborative efforts, its emergence and stability remain elusive. By peer
      punishment the sanctioning is something an individual elects to do depending on
      the strategies in its neighborhood. The consequences of unsustainable efforts are
      therefore local. By pool-punishment, on the other hand, where resources for
      sanctioning are committed in advance and at large, the notion of sustainability
      has greater significance. In a population with free-riders, punishers must be
      strong in numbers to keep the "punishment pool" from emptying. Failure to do so
      renders the concept of institutionalized sanctioning futile. We show that pool
      punishment in structured populations is sustainable, but only if second-order
      free-riders are sanctioned as well, and to a such degree that they cannot
      prevail. A discontinuous phase transition leads to an outbreak of sustainability
      when punishers subvert second-order free-riders in the competition against
      defectors.

PMID- 22468229
TI  - Functionally Distinct Subpopulations of CpG-Activated Memory B Cells.
AB  - During the human B cell (Bc) recall response, rapid cell division results in
      multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined
      with cytokines, causes Bc activation and division in vitro and increased CD27
      surface expression in a sub-population of Bc. We hypothesized that the
      proliferating CD27(lo) subpopulation, which has a lower frequency of antibody
      secreting cells (ASC) than CD27(hi) plasmablasts, provides alternative functions
      such as cytokine secretion, costimulation, or antigen presentation. We performed
      genome-wide transcriptional analysis of CpG activated Bc sorted into undivided,
      proliferating CD27(lo) and proliferating CD27(hi) subpopulations. Our data
      supported an alternative hypothesis, that CD27(lo) cells are a transient pre
      plasmablast population, expressing genes associated with Bc receptor editing.
      Undivided cells had an active transcriptional program of non-ASC B cell
      functions, including cytokine secretion and costimulation, suggesting a link
      between innate and adaptive Bc responses. Transcriptome analysis suggested a gene
      regulatory network for CD27(lo) and CD27(hi) Bc differentiation.

PMID- 22468230
TI  - Having a pair: the key to immune evasion for the diploid pathogen Schistosoma
      japonicum.
AB  - Schistosomes, unlike malaria parasites, are in their diploid stage when targeted
      by the human immune system. Diploids can be either homozygous or heterozygous.
      The difference has profound significance for developing immunity and yet has not
      previously been addressed. We examined the implications of zygosity on immunity
      to a diploid pathogen, Schistosoma japonicum and showed that the diploid state,
      and its associated heterozygous advantage, significantly affects the outcome of
      attack by the immune system and the accumulation of antigenic diversity in the
      parasite population. We demonstrate here that diploidy provides a novel means of
      immune evasion for diploid pathogens.

PMID- 22468231
TI  - Induction of Mitochondrial Pathways and Endoplasmic Reticulum Stress for
      Increasing Apoptosis in Ectopic and Orthotopic Neuroblastoma Xenografts.
AB  - Cancers are characterized by dysregulation of multiple signaling pathways and
      thus monotherapies are hardly effective. Neuroblastoma, which often occurs in
      adrenal glands, is the most common childhood malignancy. Malignant neuroblastoma
      resists traditional treatments and further studies are needed for effective
      therapeutic interventions. We evaluated synergistic efficacy of N-(4
      hydroxyphenyl) retinamide (4-HPR) and genistein (GST) for induction of apoptosis
      in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells in culture and
      activation of multiple pathways for increasing apoptosis in ectopic and
      orthotopic neuroblastoma xenografts in nude mice. Combination of 4-HPR and GST
      synergistically reduced cell viability, caused subG1 accumulation, increased
      caspase-3 activity for apoptosis in vitro and reduced tumor growth in vivo.
      Western blotting indicated that combination therapy down regulated Id2 to induce
      differentiation, increased pro-apoptotic Bax and decreased anti-apoptotic Bcl-2
      leading to an increase in Bax:Bcl-2 ratio, increased mitochondrial Bax level,
      caused mitochondrial release of Smac/Diablo, down regulation of the baculovirus
      inhibitor-of-apoptosis repeat containing (BIRC) proteins such as BIRC-2 and BIRC
      3, and activation of calpain and caspase-3 in SH-SY5Y xenografts. Accumulation of
      apoptosis-inducing-factor (AIF) in cytosol and increase in caspase-4 activation
      suggested involvement of mitochondrial pathway and endoplasmic reticulum (ER)
      stress, respectively, for apoptosis in SH-SY5Y xenografts. In situ
      immunofluorescent labelings of SH-SY5Y and SK-N-BE2 xenograft sections showed
      overexpression of calpain, caspase-12, and caspase-3, and AIF, suggesting
      induction of mitochondrial caspase-dependent and caspase-independent pathways for
      apoptosis. Collectively, synergistic effects of 4-HPR and GST induced
      mitochondrial pathways and also ER stress for increasing apoptosis in ectopic and
      orthotopic neuroblastoma xenografts in nude mice.

PMID- 22468232
TI  - Chiral N-Heterocyclic Carbene Catalyzed Annulations of Enals and Ynals with
      Stable Enols: A Highly Enantioselective Coates-Claisen Rearrangement.
AB  - A combination of a chiral N-heterocyclic carbene catalyst and alpha,beta
      unsaturated aldehyde leads to a catalytically generated alpha,beta-unsaturated
      acyl azolium, which participates in a highly enantioselective annulation to give
      dihydropyranone products. This full account of our investigations into the scope
      and mechanism of this reaction reveals the critical role of both the type and
      substitution pattern of the chiral triazolium precatalyst in inducing and
      controlling the stereochemistry. In an effort to explain why stable enols such as
      naphthol, kojic acid, and dicarbonyl are uniquely efficient, we have postulated
      that this annulation occurs via a Coates-Claisen rearrangement that invokes the
      formation of a hemiacetal prior to a sigmatropic rearrangement. Detailed kinetic
      investigations of the catalytic annulation are consistent with this mechanistic
      postulate.

PMID- 22457847
TI  - Voluntary wheel running in dystrophin-deficient (mdx) mice: Relationships between
      exercise parameters and exacerbation of the dystrophic phenotype.
AB  - Voluntary wheel running can potentially be used to exacerbate the disease
      phenotype in dystrophin-deficient mdx mice. While it has been established that
      voluntary wheel running is highly variable between individuals, the key
      parameters of wheel running that impact the most on muscle pathology have not
      been examined in detail. We conducted a 2-week test of voluntary wheel running by
      mdx mice and the impact of wheel running on disease pathology. There was
      significant individual variation in the average daily distance (ranging from
      0.003 +/- 0.005 km to 4.48 +/- 0.96 km), culminating in a wide range (0.040 km to
      67.24 km) of total cumulative distances run by individuals. There was also
      variation in the number and length of run/rest cycles per night, and the average
      running rate. Correlation analyses demonstrated that in the quadriceps muscle, a
      low number of high distance run/rest cycles was the most consistent indicator for
      increased tissue damage. The amount of rest time between running bouts was a key
      factor associated with gastrocnemius damage. These data emphasize the need for
      detailed analysis of individual running performance, consideration of the length
      of wheel exposure time, and the selection of appropriate muscle groups for
      analysis, when applying the use of voluntary wheel running to disease
      exacerbation and/or pre-clinical testing of the efficacy of therapeutic agents in
      the mdx mouse.

PMID- 22468233
TI  - Regulation of Immune Responses by Spontaneous and T cell-mediated Dendritic Cell
      Death.
AB  - In response to antigen stimulations, cells in the immune system undergo dynamic
      activation, differentiation, expansion and turnover. Programmed cell death is
      important for maintaining homeostasis of different cell types in the immune
      system. Dendritic cells (DCs) are a heterogeneous population of antigen
      presenting cells that capture, process and present antigens to stimulate
      lymphocytes. DCs have also emerged as major regulators of both innate and
      adaptive immune responses. Conventional myeloid DCs are relatively short-lived
      compared to lymphocytes in lymphoid organs. Mitochondrion-dependent apoptosis
      governed by Bcl-2 family members plays a major role in regulating spontaneous DC
      turnover. Killing of DCs by antigen-specific T cells also provides a negative
      feedback mechanism to restrict the duration and the scope of immune responses.
      Defects in cell death in DCs lead to DC accumulation, resulting in overactivation
      of lymphocytes and the development of autoimmunity in mice. Programmed cell death
      in DCs may play essential roles in the regulation of the duration and magnitude
      of immune responses, and in the protection against autoimmunity and uncontrolled
      inflammation.

PMID- 22457847
TI  - Voluntary wheel running in dystrophin-deficient (mdx) mice: Relationships between
      exercise parameters and exacerbation of the dystrophic phenotype.
AB  - Voluntary wheel running can potentially be used to exacerbate the disease
      phenotype in dystrophin-deficient mdx mice. While it has been established that
      voluntary wheel running is highly variable between individuals, the key
      parameters of wheel running that impact the most on muscle pathology have not
      been examined in detail. We conducted a 2-week test of voluntary wheel running by
      mdx mice and the impact of wheel running on disease pathology. There was
      significant individual variation in the average daily distance (ranging from
      0.003 +/- 0.005 km to 4.48 +/- 0.96 km), culminating in a wide range (0.040 km to
      67.24 km) of total cumulative distances run by individuals. There was also
      variation in the number and length of run/rest cycles per night, and the average
      running rate. Correlation analyses demonstrated that in the quadriceps muscle, a
      low number of high distance run/rest cycles was the most consistent indicator for
      increased tissue damage. The amount of rest time between running bouts was a key
      factor associated with gastrocnemius damage. These data emphasize the need for
      detailed analysis of individual running performance, consideration of the length
      of wheel exposure time, and the selection of appropriate muscle groups for
      analysis, when applying the use of voluntary wheel running to disease
      exacerbation and/or pre-clinical testing of the efficacy of therapeutic agents in
      the mdx mouse.

PMID- 22468236
TI  - Fatigue as a core symptom of insomnia.

PMID- 22468237
TI  - Illicit drug use in teenagers and young adults.

PMID- 22468238
TI  - Histories of rages and disruptive behaviors in the medical setting.

PMID- 22468239
TI  - Psychiatric effects of military deployment on children and families: the use of
      play therapy for assessment and treatment.
AB  - Deployments in the United States military have increased greatly in the past 10
      years. Families and children are psychiatrically affected by these deployments,
      and recent studies are clarifying these effects. This article focuses on the
      psychiatric effects of deployment on children and uses a composite case example
      to review the use of play therapy to treat children who are having psychiatric
      issues related to the deployment of one or both parents.

PMID- 22468240
TI  - It's only a little ice: a personal view with companion commentary.
AB  - First, parallels are drawn between the conduct of clinical trials and a few
      events in history that share a management style known as "top-down" management or
      a hierarchal decision-making process. The author suggests that this process
      isolates investigative sites from sponsors and contributes to the failure of
      clinical trials. Trial design, patient recruitment, site selection, the use of
      electronic data devices, and enrollment timelines are examined in greater detail.
      Suggestions for a more open or shared process are offered, with the belief that
      fewer trials might fail and fewer questions might remain in the case of those
      that do.Next, in the companion commentary, some of the problems arising in drug
      development and clinical trials are mentioned along with a partial listing of
      solution providers. An outline of circumstances involved in the decision-making
      process in drug development are presented along with some factors leading to
      decreased signal detection.

PMID- 22468241
TI  - The development of posttraumatic stress disorder following an unusual life event:
      a case report.
AB  - Posttraumatic stress disorder is the only psychiatric disorder, according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, that
      requires a specific life-threatening event to have occurred prior to diagnosing
      the illness. The traumatic event is described as an experience of witnessing
      either the occurrence, or imminent threat, of serious injury or death. This case
      report describes the development of posttraumatic stress in a middle-aged man,
      with no prior psychiatric history, after he ingested part of a candy bar he later
      discovered to be infested with maggots. This case report adds to the literature
      supporting a broader diagnostic view of posttraumatic stress in the absence of
      life-threatening stressors.

PMID- 22468243
TI  - Overwork suicide in Japan: a national crisis.

PMID- 22468242
TI  - Rumination: relationships with physical health.
AB  - Rumination is a form of perserverative cognition that focuses on negative
      content, generally past and present, and results in emotional distress. Initial
      studies of rumination emerged in the psychological literature, particularly with
      regard to studies examining specific facets of rumination (e.g., positive vs.
      negative rumination, brooding vs. self-reflection, relationships with
      catastrophic thinking, role of impaired disengagement, state vs. trait features)
      as well as the presence of rumination in various psychiatric syndromes (e.g.,
      depression, alcohol misuse, generalized anxiety disorder, social anxiety
      disorder, obsessive compulsive disorder, posttraumatic stress disorder, bulimia
      nervosa). Rumination studies are now emerging in the somatic literature,
      particularly in relationship to pain. In these studies, rumination appears to be
      associated with symptom magnification as well as poorer clinical outcomes. While
      still a nascent field, the assessment and treatment of rumination in primary care
      settings is beginning to unfold.

PMID- 22468244
TI  - Endoscopic anatomy of the middle ear.
AB  - Good knowledge of anatomy is fundamental for every surgeon. Middle ear anatomy is
      really complex and sometimes is challenging for otologists, who need to explore
      every single compartment for a radical removal of pathology. With introduction of
      the endoscope in middle ear surgery, anatomy of middle ear spaces has become
      wider and clearer due to a better magnification and to the possibility to look
      "behind the corner". This article is a review of the state-of-art of endoscopic
      middle ear anatomy with description of every compartment, with particular
      attention to ventilation pathways and middle ear folds.

PMID- 22468245
TI  - A Single Blinded Randomized Controlled Study of the Effect of Conventional Oral
      Hypoglycemic Agents Versus Intensive Short-Term Insulin Therapy on Pure Tone
      Audiometry in Type II Diabetes Mellitus.
AB  - Neuropathy is frequently a late complication of diabetes mellitus. Auditory
      neuropathy and microangiopathy of inner ear are the possible causes of hearing
      loss in diabetics. To study the correlation between glycaemic control and hearing
      threshold in patients with type 2 diabetes mellitus and to determine the
      differences of hearing threshold between groups treated with different modality.
      This single blind randomized controlled study was performed at the Department of
      Medicine and Department of Otorhinolaryngology, Hospital Universiti Kebangsaan
      Malaysia (UKM) between 1st May 2003 and 31st September 2004. This study was
      approved by Research Ethics Committee (code number FF-137). Subjects were
      randomized into two groups. Group 1 were patients treated with conventional oral
      hypoglycemic agents. The patients in group 2 were those treated with insulin
      injection. The subjects were seen 4 weekly for 3 months. Audiometric test were
      performed in all subjects at each visit. Blood were taken for fasting blood
      glucose, Hb1Ac, and fructosamine at every visit to determine the glycaemic
      controls of the subject. They were 11 patients (22 ears) treated with oral
      hypoglycemic agents and 17 patients treated (34 ears) with subcutaneous insulin.
      There is no significant difference between mean pure tone threshold before and
      after treatment at all frequencies in both groups. There is also no significance
      different in fasting glucose level and fructosamine. However, there is
      significant difference HbA1c levels between the two groups after treatment (P <
      0.05). This study has shown that glycaemic control does not have significant
      impact on hearing. The hearing threshold is neither affected by insulin treatment
      nor by the glycaemic control.

PMID- 22468246
TI  - Analysis of lower airway inflammation in a rabbit model of acute rhinosinusitis.
AB  - This study aimed to investigate the association of inflammatory changes of upper
      and lower airways in a rabbit model of acute rhinosinusitis. The study included
      six adult albino rabbits. The sinuses of one animal were injected with saline
      solution and the animal was served as sham control. Other animals were implanted
      with intranasal S. aureus soaked-absorbable gelatin sponge. Acute rhinosinusitis
      was induced and subjects were sacrificed at the end of the second week. Tissue
      samples from all levels of the airway were obtained. They were evaluated for the
      presence of inflammatory changes histologically. A scoring system for airway
      inflammation was used for quantitative assessment of the degree of inflammation.
      Structural changes in the epithelial and stromal layers of the upper and lower
      airway structures were analyzed, as well. The animal of which the sinuses were
      injected with saline solution developed neither acute rhinosinusitis nor lower
      airway inflammation. In contrast, the animals in which acute rhinosinusitis was
      induced demonstrated significant upper and lower airway inflammation
      histologically. Inflammatory changes ranged from engorgement of blood vessels and
      polymorphonuclear cell proliferation within the capillaries, in the perivascular
      tissue of the epithelium or in the lamina propria and to epithelial disruption.
      Nasal airway inflammation scores (2.86 +/- 1.81) were significantly higher than
      lower airway scores (1.36 +/- 0.77), (P < 0.01). We obtained a generalized
      mucosal inflammatory response against localized bacterial inflammation in a
      rabbit model of acute rhinosinusitis, confirming the suggestion of 'one airway-
      one disease' from a bacterial infection point of view.

PMID- 22468247
TI  - Treatment of otosclerosis with a superelastic nitinol piston: first results.
AB  - Stapedotomy with implantation of an alloplastic prosthesis is a well-established
      therapy for the treatment of otosclerosis. Since the middle of 2008, a new
      Nitinol prosthesis with memory function and superelastic properties has been
      available which is expected to make fixation on the long process of the incus
      much easier. The advantage of this prosthesis is that heat-induced wire crimping
      is no longer necessary and damage to the incus caused by heat is avoided. Since
      May 2008, laser-assisted stapedotomy with implantation of a Nitinol prosthesis
      was performed in 21 patients suffering from otosclerosis. The prostheses used for
      all patients had a size of 4.5 mm * 0.4 mm. The patient collective consisted of
      14 women and 7 men with a mean age of 53.4 years. Pre- and postoperatively, an
      ENT examination was carried out followed by an audiological evaluation of the
      hearing result. In addition, the properties of the prosthesis ("proper fitt",
      "handling", and "overall rating") were evaluated intraoperatively by means of a
      test protocol. The Nitinol prosthesis was implanted successfully in all 21
      patients. The mean air-bone gap for the frequencies from 0.5 to 4 kHz was 9.83 dB
      postoperatively. Intraoperatively, the fit of the prosthesis was rated as "good
      to very good", the handling as "good" and the overall rating of the system was
      "good to very good". Our patient collective showed good postoperative hearing
      results. Due to simple intraoperative handling, especially placing the Nitinol
      prosthesis in position, the critical work step of crimping is no longer
      necessary.

PMID- 22468248
TI  - Skin prick testing and immunotherapy in nasobronchial allergy: our experience.
AB  - In the present study of 331 patients suffering from signs/symptoms of nasal
      allergy, 9 nasal polyps, allergic conjunctivitis and allergic asthma, who were
      referred by clinician, were taken up for diagnosis of allergy with skin prick
      test (Ten et al. Mayo Clin Proc 70(8):783-784, 1995) and subjective improvement
      of patients by immunotherapy. Out of 331 patients tested 321 patients showed
      significant positive results and rest of them tested negative for allergy. High
      incidences of positive results were noted in third and fourth decade age of
      patients. Dust and pollen allergens were positive in most of the patients compare
      to insect's antigens. Among the pollen antigens tested, those of Parthenium
      hysterophorus was found to be the most common (30%) followed by Prosopis julifora
      (25%). 75.22% patients were positive to house dust, 19.33% patients were positive
      to Aspergillusmoulds. D. farinae was the most common offender amongst the mites.
      Patients who attended, allergy clinic in Kamineni Hospitals during the last 4
      years were referral patients, who had been on prolonged treatment without much
      relief. Immunotherapy was advised to patients who were having perineal allergy,
      in whom, medical treatment had become only palliative. Immunotherapy injections
      were administered subcutaneously, and their results were monitored.

PMID- 22468249
TI  - Study on the anatomical variations of the posterosuperior bony overhang of
      external auditory canal.
AB  - To evaluate the extent of posterosuperior bony overhang required to be removed
      for proper exposure of the incudo-stapedial complex during stapes surgery.
      Whether an assessment can be made out about the extent of the posterosuperior
      bony overhang clinically or not. A prospective study. One hundred patients of
      Stapedial Otosclerosis were included in this study. The direction of the
      posterosuperior bony canal wall i.e. straight or sloping type was recorded in
      every patient. All the patients underwent stapedotomy operation under local
      anaesthesia. The amount of overhang of the posterosuperior bony canal wall
      required to be removed for adequate exposure of the incudo-stapedial complex
      during stapes surgery was recorded by using measured right-angled picks of
      different sizes in mm. The aim of this study is to find out the extent of
      posterosuperior bony overhang and to know whether the posterosuperior bony
      overhang is more in straight or sloping bony canal wall. Fifty-seven percent of
      our patients had a medially sloping posterosuperior bony canal wall and 43% had a
      straight canal wall, which was noted clinically before surgery. The extent of
      posterosuperior bony overhang was divided into 4 groups: Gr. A <=2 mm, Gr. B 2
      2.5 mm, Gr. C 2.5-3 mm, Gr. D >=3 mm. There were 25 patients in Group A, 55 in
      Group B, 20 in Group C and none in Group D. So majority (i.e. 55%) patients
      belonged to Group B i.e. 2-2.5 mm. The posterosuperior bony overhang is more in
      those patients who had straight bony canal than those who had sloping bony canal.
      This may be clinically assessed and this observation is statistically significant
      (P < 0.001).

PMID- 22468250
TI  - Endoscopic management of posterior epistaxis.
AB  - The traditional method of management of posterior epistaxis has been with
      anteroposterior nasal packing. Apart from the high failure rate of 26-50%
      reported in various series, nasal packing is associated with marked discomfort
      and several complications. In order to avoid nasal packing, we started doing
      endoscopic cauterization in cases of posterior epistaxis. A total of 23 patients
      with posterior epistaxis were subjected to nasal endoscopy with the intent to
      stop bleeding by cauterization of the bleeding vessel. Of these, in four cases
      unsuspected diagnosis was made. Of the remaining 19, in three patients, the
      bleeding point could not be localized accurately and these patients were managed
      by anteroposterior packing. The rest of the 16 patients were managed by
      endoscopic cauterization. In four patients, there was recurrence of bleeding
      within 24 h. In one of these, cauterization controlled the bleeding while in the
      rest nasal packing had to be resorted to. Thus, of the 23 patients of posterior
      epistaxis subjected to nasal endoscopy, we could avoid nasal packing in 17 (74%).
      To conclude, endoscopic nasal cauterization is recommended as the first line to
      treatment in all cases of posterior epistaxis. This will not only prevent the
      uncomfortable and potentially dangerous nasal packing but also help in finding
      the underlying pathology.

PMID- 22468251
TI  - Treatment delay in oral and oropharyngeal cancer in our population: the role of
      socio-economic factors and health-seeking behaviour.
AB  - The objective is to assess the role of socio-economic factors and health-seeking
      behavior in treatment delay in oral and oropharyngeal cancer in our population.
      This article adapts-design: prospective study and setting: tertiary care centre.
      We studied 153 patients with oral and oropharyngeal squamous cell carcinoma who
      were managed in the department of otolaryngology and head and neck surgery
      between January 2006 and December 2007. There were 127 male patients (83%) and 26
      females (17%) with ages ranging from 22 years to 70 years. Fifty-nine patients
      (39%) presented to us with early stage disease (i.e. stage I and II), whereas, 94
      patients (61%) presented with late stage disease (i.e. stage III and IV). Of the
      59 patients presenting with early stage disease, 20 were illiterate and 39
      literate with 28 patients (47%) belonging to low socio-economic status and 32
      patients (54%) having an access to primary health centre (PHC). Of the 94
      patients presenting with late stage disease, 53 were illiterate and 41 literate
      with 58 patients (62%) belonging to low socio-economic status and 38 patients
      (40%) having an access to primary health centre. Literacy, socio-economic status,
      access to primary health centre and health-seeking behavior of our population has
      a significant association with the stage of presentation of patients with oral
      and oropharyngeal cancer.

PMID- 22468252
TI  - Ototoxic effects of irradiation.
AB  - In this study ototoxic effect of ionizing radiation was studied in 70 ears with
      minimum follow up of 6 months post radiotherapy. Patients of nasopharyngeal
      carcinoma and with conductive deafness pre radiotherapy were excluded from the
      study to eliminate mechanical obstruction that may play role in Eustachian tube
      dysfunction. We found that Eustachian tube dysfunction and conductive deafness
      were reversible where as Sensorineural hearing loss was an irreversible effect of
      radiotherapy. Dose of radiation was directly proportional to ototoxicity, minimum
      60 Gys of total radiation dose was required to produce significant ototoxicity.

PMID- 22468253
TI  - Correlative Study of HRCT in Attico-Antral Disease.
AB  - There is lot of controversy over the utility of pre-operative radiology in
      management of attico-antral disease. This study was done to find correlation
      between pre-operative HRCT and intra-operative findings in patients with attico
      antral disease. Study revealed varying degrees of sensitivity and sensitivity for
      different aspects of the disease. We conclude that though HRCT given good
      visualization of the key areas, high levels of false positive and false negative
      prevent the wholesome reliability on it.

PMID- 22468254
TI  - Comparing the efficacy of alkaline nasal douches versus decongestant nasal drops
      in postoperative care after septal surgery: a randomised single blinded clinical
      pilot study.
AB  - To compare the efficacy of alkaline nasal douches and decongestant nasal drops
      following nasal septal surgery. This was a prospective, randomised, single-blind
      pilot study. Twenty patients were included in each arm of the study undergoing
      elective nasal septal surgery. The primary outcome measure was nasal congestion.
      Secondary outcome measures were anosmia, facial pain, nasal discharge, and
      sneezing/itching. This study does not show any statistically significant
      difference between the two treatment groups. Symptoms of nasal congestion (P =
      0.3), facial pain (P = 0.932), nasal discharge (P = 0.98), sneezing (P = 0.59)
      and anosmia (P = 0.208) were analysed before conclusion. Three patients in saline
      group and one patient in the nasal drops group had poor compliance to follow the
      advice, scoring 2 on a VAS score but the treatment was tolerated well in majority
      of the patients. No statistical significant differences were noted on analysing
      the post operative complications in either group. In this study, both nasal
      douches and decongestant nasal drop were well tolerated. Both treatments provided
      good postoperative relief from nasal congestion, nasal discharge, sneezing,
      facial pain and anosmia as days progressed. The post operative examination of the
      nose among these patients revealed no significant complications in either of the
      study arm.

PMID- 22468255
TI  - Intelligibility and acoustic characteristics of clear and conversational speech
      in telugu (a South Indian dravidian language).
AB  - The overall goal of this study is to examine the intelligibility differences of
      clear and conversational speech and also to objectively analyze the acoustic
      properties contributing to these differences. Seventeen post-lingual stable
      sensory-neural hearing impaired listeners with an age range of 17-40 years were
      recruited for the study. Forty Telugu sentences spoken by a female Telugu speaker
      in both clear and conversational speech styles were used as stimuli for the
      subjects. Results revealed that mean scores of clear speech were higher (mean =
      84.5) when compared to conversational speech (mean = 61.4) with an advantage of
      23.1% points. Acoustic properties revealed greater fundamental frequency (f0) and
      intensity, longer duration, higher consonant-vowel ratio (CVR) and greater
      temporal energy in clear speech.

PMID- 22468256
TI  - Evaluation of p53, p63, p21, p27, ki-67 in paranasal sinus squamous cell
      carcinoma and inverted papilloma.
AB  - Using a molecular genetic approach, we try to confirm the molecular alterations
      of inverted papilloma and clarify its status as a putative precursor lesion of
      sinonasal squamous cell carcinoma. To better understand its genetics, we
      investigated the immunohistochemical protein expression patterns of cell-cycle
      regulators p53, p63, p21, p27 and proliferation marker Ki-67 in 22 inverted
      papilloma and 9 squamous cell carcinoma of the sinonasal tract. Significantly
      elevated levels of p53 and p63 in squamous cell carcinoma of sinonasal tract
      compared with inverted papilloma were revealed. Ki-67-stained neoplastic cell
      nuclei were found in a significantly higher percentage of squamous cell carcinoma
      of sinonasal tract than in inverted papilloma, whereas no variation of p21 and
      p27 expression was identified. This work first examined the immunohistochemical
      overexpression of p63 in sinonasal inverted papilloma and squamous cell
      carcinoma. In conclusion, this is a first study shedding light on the expression
      of p63 in tumors of paranasal sinuses.

PMID- 22468257
TI  - Transcervical tongue base reduction with hyoepiglottoplasty: long-term results.
AB  - Aims To evaluate the long term results of tongue base reduction with
      hyoepiglottoplasty as a surgical option in the treatment of severe obstructive
      sleep apnea. Material and Method Severe obstructive sleep apnea patients
      diagnosed as upper airway narrowing at the tongue base level were treated with
      transcervical tongue base reduction with hyoepiglottoplasty. Seven years after
      single stage multilevel surgery, the patients were reevaluated clinically,
      radiologically and polysomnographic records were taken. Preoperative, early
      postoperative and long-term postoperative parameters were compared to determine
      the success rate of the surgical technique. Results In the postoperative long
      term follow-up Epworth sleepiness scale (ESS) scores were reduced to 4 and 6
      respectively 2 months after surgery despite the initial values of 17 and 15. BMI
      were decreased from 29.7 and 27.9 kg/m(2) respectively to 26 and 24 kg/m(2). The
      apnea/hypopnea index (AHI) were reduced to 14.1 and 16.2 respectively from 68.6
      and 83.83. O(2) nadir was 55 and 66% respectively and improved to 86 and 89%.
      Flexible nasopharyngoscopy revealed competent airway in both retropalatal and
      retroglossal level. Bed partners scored snoring as 2/10 and 4/10 corresponding to
      very mild and moderate. Daytime somnolence and witnessed apneic periods were
      completely disappeared in both patients. Conclusion Open tongue base resection
      with hyoepiglottoplasty is effective among all other surgical corrections of
      sleep apnea even after 7 years postoperatively.

PMID- 22468258
TI  - Clinical manifestations and role of proton pump inhibitors in the management of
      laryngopharyngeal reflux.
AB  - Laryngopharyngeal reflux (LPR) refers to the backflow of stomach contents into
      the throat that is into the hypopharynx. LPR is different from classical
      Gastroesophageal reflux disease (GERD) in many ways. Proton pump inhibitors have
      become the treatment of choice even though conflicting results exists in their
      response. Treatment requires acid suppression to be as complete as possible and
      treatment failure is not uncommon. In this article we present here our
      prospective study of 50 patients diagnosed as a case of LPR on the basis of
      reflux finding score and reflux symptom index. We tried to evaluate the role of
      PPI in LPR management by observing the effect of PPI on reflux finding score
      (RFS) and reflux symptom index (RFI) during the follow up period of 16 weeks.

PMID- 22468259
TI  - A comparative review of treatment of 80 mandibular angle fracture fixation with
      miniplates using three different techniques.
AB  - Standard treatment of mandibular angle fracture with miniplates according to
      recommendations of Champy et al. (1976) consists of fixation with one miniplate
      at superior border of mandible ventral to external oblique line. In certain
      constellations, second miniplate at lower border may provide additional
      stability. In this retrospective study 80 patients with mandibular angle fracture
      were divided into 3 sub-groups reported at DIRDS Faridkot were treated by
      intraoral, extraoral and combined intraoral and transbuccal approach. There was
      no significant difference in complication rates encountered with these
      techniques. Decision regarding treatment approaches for open reduction of
      mandible fracture often relates to surgeon's experience and training. In some
      cases, choice is affected by availability of equipment. More difficult cases
      involving endentulous atrophic mandible or comminution should be considered for
      extraoral approach. Intraoral open reduction and fixation was used for non
      comminuted and non-complicated fractures. The combined transbuccal/Intraoral
      procedure is now preferred method because of ease of use and facilitation of
      placement of plate in neutral mid point area of mandible.

PMID- 22468260
TI  - Head and neck teratomas in children: a case series.
AB  - Teratomas of the head and neck due to their obscure origin, bizarre microscopic
      appearance, unpredictable behaviour and often dramatic clinical presentation are
      a clinical surprise. This article focuses on pediatric head and neck teratomas
      and on their diversity and rarity and also reviews the recent terminology of this
      group of tumours.

PMID- 22468261
TI  - Thyroid hemiagenesis: report of a case and review of literature.
AB  - Our objective was to report an incidental finding of thyroid hemiagenesis in a
      patient who presented with a left neck mass, present a review of literature, and
      to discuss management of this diagnosis. Case report and review of literature. An
      internet-based literature search was performed via Pubmed with key words,
      "hemithyroid agenesis, thyroid hemiagenesis, absent thyroid gland". Clinical,
      pathological, radiologic data and follow up information is reported. A 55 year
      old woman with a left neck mass presented to our service. A diagnostic CT scan of
      the head and neck revealed an unrelated finding of an absent left thyroid lobe. A
      review of the CT imaging did not reveal ectopic thyroid tissue. A complete
      physical examination including a flexible laryngoscopy was unremarkable. The neck
      mass was pathologically a granulomatous lesion on surgical pathology. Thyroid
      function tests were within normal limits. In follow-up, patient remains
      asymptomatic. Hemithyroid agenesis is most commonly associated with
      hyperthyroidism, although, hypothyroidism has been reported. Pathology that can
      be associated in the remnant thyroid lobe includes adenocarcinoma, adenoma,
      multinodular goiter, and chronic thyroiditis. In counseling patients, it is
      important to educate them regarding these associated conditions and offer
      appropriate work up if indicated. Incidental thyroid agenesis with a negative
      work up can then be observed.

PMID- 22468262
TI  - Modeling human exposure levels to airborne volatile organic compounds by the
      hebei spirit oil spill.
AB  - OBJECTIVES: The goal was to model and quantify the atmospheric concentrations of
      volatile organic compounds (VOCs) as the result of the Hebei Spirit oil spill,
      and to predict whether the exposure levels were abnormally high or not. METHODS:
      We developed a model for calculating the airborne concentration of VOCs that are
      produced in an oil spill accident. The model was applied to a practical
      situation, namely the Hebei Spirit oil spill. The accuracy of the model was
      verified by comparing the results with previous observation data. The
      concentrations were compared with the currently used air quality standards.
      RESULTS: Evaporation was found to be 10- to 1,000-fold higher than the emissions
      produced from a surrounding industrial complex. The modeled concentrations for
      benzene failed to meet current labor environmental standards, and the
      concentration of benzene, toluene, ortho- meta- para-xylene were higher than the
      values specified by air quality standards and guideline values on the ocean. The
      concentrations of total VOCs were much higher than indoor environmental criteria
      for the entire Taean area for a few days. CONCLUSIONS: The extent of airborne
      exposure was clearly not the same as that for normal conditions.

PMID- 22468264
TI  - Two-dimensional pH-responsive printable smectic hydrogels.
AB  - Anisotropic swelling and deswelling of smectic liquid crystal networks have been
      observed in response to pH changes.

PMID- 22468265
TI  - Synthesis and characterization of ratiometric nanosensors for pH quantification:
      a mixed micelle approach.
AB  - Optical nanoparticle pH sensors designed for ratiometric measurements have
      previously been synthesized using post-functionalization approaches to introduce
      sensor molecules and to modify nanoparticle surface chemistry. This strategy
      often results in low control of the nanoparticle surface chemistry and is prone
      to batch-to-batch variations, which is undesirable for succeeding sensor
      calibrations and cellular measurements. Here we provide a new synthetic approach
      for preparing nanoparticle pH sensors based on self-organization principles,
      which in comparison to earlier strategies offers a much higher design flexibility
      and high control of particle size, morphology and surface chemistry.

PMID- 22468266
TI  - Predictable self-assembled [2*2] Ln(III)4 square grids (Ln = Dy,Tb)-SMM behaviour
      in a new lanthanide cluster motif.
AB  - The ditopic carbohydrazone ligand (L1) produces the square, self-assembled [2*2]
      grids [Dy(4)(L1)(4)(OH)(4)]Cl(2) (1) and [Ln(4)(L1)(4)(MU(4)-O)(MU(2)-1,1
      N(3))(4)] (Ln = Dy (2), Tb (3)), with 2 exhibiting SMM behaviour. Two relaxation
      processes occur with U(eff) = 51 K, 91 K in the absence of an external field, and
      one with U(eff) = 270 K in the presence of a 1600 Oe optimum field.

PMID- 22468267
TI  - Characterization of the Group A Streptococcus Mga virulence regulator reveals a
      role for the C-terminal region in oligomerization and transcriptional activation.
AB  - The Group A Streptococcus (GAS) is a strict human pathogen that causes a broad
      spectrum of illnesses. One of the key regulators of virulence in GAS is the
      transcriptional activator Mga, which co-ordinates the early stages of infection.
      Although the targets of Mga have been well characterized, basic biochemical
      analyses have been limited due to difficulties in obtaining purified protein. In
      this study, high-level purification of soluble Mga was achieved, enabling the
      first detailed characterization of the protein. Fluorescence titrations coupled
      with filter-binding assays indicate that Mga binds cognate DNA with nanomolar
      affinity. Gel filtration analyses, analytical ultracentrifugation and co
      immunoprecipitation experiments demonstrate that Mga forms oligomers in
      solution.Moreover, the ability of the protein to oligomerize in solution was
      found to correlate with transcriptional activation; DNA binding appears to be
      necessary but insufficient for full activity. Truncation analyses reveal that the
      uncharacterized C-terminal region of Mga, possessing similarity to
      phosphotransferase system EIIB proteins, plays a critical role in oligomerization
      and in vivo activity. Mga from a divergent serotype was found to behave
      similarly, suggesting that this study describes a general mechanism for Mga
      regulation of target virulence genes within GAS and provides insight into related
      regulators in other Gram-positive pathogens.

PMID- 22468269
TI  - Identification of a novel HLA-DRB3 allele, DRB3*02:27, in a potential
      haematopoietic stem cell transplant recipient.

PMID- 22468268
TI  - Comprehensive resequence analysis of a 123-kb region of chromosome 11q13
      associated with prostate cancer.
AB  - BACKGROUND: Genome-wide association studies of prostate cancer have identified
      single nucleotide polymorphism (SNP) markers in a region of chromosome 11q13.3 in
      men of European decent. A fine-mapping analysis with tag SNPs in the cancer
      genetic markers of susceptibility study identified three independent loci, marked
      by rs10896438, rs12793759, and rs10896449. This study further annotates common
      and uncommon variation across this region. METHODS: A next generation resequence
      analysis of a 122.9-kb region of 11q13.3(68,642,755-68,765,690) was conducted in
      78 unrelated individuals of European background,1 CEPH trio, and 1 YRI trio.
      RESULTS: In total, 644 polymorphic loci were identified by our sequence analysis.
      Of these,166 variants-118 SNPs and 48 insertion-deletion polymorphisms (indels)
      were novel,namely not present in the 1000 Genomes or International HapMap
      Projects. We identified 22,25, 6, and 4 variants strongly correlated (r2 >= 0.8)
      with rs10896438, rs10896449, rs12793759,and rs11228565, respectively. HapMap SNPs
      were in linkage disequilibrium (r2 >= 0.8) with 48%, 69%, 14%, and 60% of SNPs
      marking bins by rs10896438, rs10896449, rs12793759, and rs11228565, respectively.
      CONCLUSIONS: Our next generation resequence analysis compliments publicly
      available datasets of European descent (HapMap, build 28 and 1000 Genome, Pilot
      1, October 2010),underscoring the value of targeted resequence analysis prior to
      initiating functional studies based on public databases alone. Increasing the
      number of common variants enables investigators to better prioritize variants for
      functional studies designed to uncover the biological basis of the direct
      association(s) in the region.

PMID- 22468270
TI  - Assessing the risk of lymph node invasion in patients with intermediate risk
      prostate cancer treated with extended pelvic lymph node dissection. A novel
      prediction tool.
AB  - BACKGROUND: Controversy exists regarding the need for extended pelvic lymph node
      dissection (ePLND) in patients with intermediate risk prostate cancer (PCa).
      MATERIALS AND METHODS: The study included 982 consecutive men with intermediate
      risk PCa (PSA 10-20 ng/ml or cT2b-c or biopsy Gleason 3 + 4/ 4 + 3) treated with
      ePLND and radical prostatectomy (RP) at a single center. All patients underwent
      an anatomically defined ePLND. A novel risk stratification tool was developed by
      applying the nonparametric tree modeling technique of classification and
      regression tree analysis (CART) which relied on pre-operative PSA, clinical
      stage, biopsy Gleason score, and percentage of positive cores. The area under the
      receiver characteristic curve (AUC) method was used to quantify the accuracy of
      the model. RESULTS: Lymph node invasion (LNI) was found in 81 (8.2%) patients.
      The CART analyses identified three risk groups of having LNI: a) Low risk:
      Gleason 3 + 3, cT1c/cT2, PSA 10-20 ng/ml, or Gleason 3 + 4/4 + 3, <= 63% of
      positive cores and PSA < 5 ng/ml (risk of LNI:3.7 and 5.2%, respectively; 64.8%
      of patients included); b) Moderate risk: Gleason 3 + 4/4 + 3, <= 63% of positive
      cores and PSA >= 5 ng/ml (risk of LNI:14.4%; 23% of patients included); c)High
      risk: Gleason 3 + 4/4 + 3, % positive cores >63% (risk of LNI:20.1%; 12.% of
      patients included; P < 0.001). The accuracy of the model was 71%. CONCLUSIONS:
      The risk of having LNI varies significantly (3.7-20.1%) in patients with
      intermediate risk PCa. Our predictive tool might help selecting those patients
      suitable fore PLND, allowing to spare this approach in about 60% of intermediate
      risk patients.

PMID- 22468271
TI  - [Overweight among children in Pakistan].

PMID- 22468272
TI  - A survey of evidence-based practise among Dutch occupational therapists.
AB  - This study explored how the evidenced-based practise (EBP) is perceived by Dutch
      occupational therapists (OTs), what sources of research data are used to make
      clinical decisions, and what barriers are identified in implementing EBP. A self
      administered, pre-tested, questionnaire was distributed through an email survey
      and postal mail among the 200 randomly stratified selected OTs out of a total
      population of 2,019 Dutch OTs. Analyses of data comprised descriptive statistics
      of all variables and test statistics to evaluate the differences between
      demographical groups. Dutch OTs have a very positive attitude toward the EBP.
      Barriers experienced are mostly related to a lack of skills needed to implement
      the EBP and to the characteristics of the work environment. The attitude,
      experiences and barriers are mainly similar to research findings in other
      countries or professions. A unique barrier to the implementation of the EBP found
      in this study was that Dutch OTs perceived evidence written in a foreign (non
      Dutch) language as a barrier to using evidence in non-Dutch languages. The
      results of the study, derived from a partly representative group of working OTs,
      implicate universal problems regarding the effective implementation of the EBP.
      Solutions to increase the implementation of the EBP from an international point
      of view are called for and need to be evaluated.

PMID- 22468273
TI  - Epigenetics: Marked for success.

PMID- 22468274
TI  - Looking for alternative energy sources.
AB  - With unrest in oil-exporting countries, backlashes against biofuels and
      photovoltaics, and a nuclear incident in Japan, the year 2011 rattled confidence
      in future energy supplies. The search for alternatives is all the more urgent,
      but some of the solutions investigated hark back to fossil fuels that we can't
      afford to burn.

PMID- 22468275
TI  - Chromatin processes, epigenetic inheritance, centromere structure  and function
      and evolution.

PMID- 22468277
TI  - H5N1 research put on hold.

PMID- 22468276
TI  - PanACEA: a new approach to tuberculosis research.

PMID- 22468278
TI  - Wouldn't have happened to a Limey.

PMID- 22468279
TI  - Retraction.

PMID- 22468280
TI  - State secrets. Feds releasing few details on insurance exchanges.

PMID- 22468281
TI  - Tackling the wage index. Coalition seeks revamp of 'rural floor' component.

PMID- 22468282
TI  - 25 busiest hospital emergency departments. Ranked by number of emergency room
      visits, 2010.

PMID- 22468283
TI  - Still no fix for SGR. Pay cuts prevented, but move irks docs, hospitals.

PMID- 22468285
TI  - Help still wanted. Feds' IT training program an untapped resource.

PMID- 22468284
TI  - Picked apart. Dems, GOP providers all slap Obama budget plan.

PMID- 22468286
TI  - Another boost for budgets. IT taking a bigger bite out of capital spending.

PMID- 22468287
TI  - Consent consensus. Providers ponder more-stringent rules on privacy.

PMID- 22468288
TI  - Largest behavioral health providers. Ranked by behavioral health net patient
      revenue.

PMID- 22468289
TI  - Shaky support. GOP candidates back new premium plan for Medicare, but details and
      impact a little fuzzy.
AB  - A variety of premium-support models for Medicare are floating around D.C. these
      days, but details are sketchy. However, now is the time for discussing such
      changes, according to one author, Sen. Ron Wyden, left, because unless lawmakers
      make fundamental changes, they must make incremental cuts "that will hurt
      seniors, will hurt healthcare providers, and that will essentially continue until
      the Medicare guarantee--and I use this word specifically--has been vaporized".

PMID- 22468290
TI  - Still in the dark. Providers, devicemakers in holding pattern on compliance
      efforts as they await final rules for the federal Sunshine Act.

PMID- 22468291
TI  - Largest U.S. medical device manufacturers. Ranked by market capitalization as of
      March 5, 2012.

PMID- 22468292
TI  - A novel type of energy metabolism involving fermentation of inorganic sulphur
      compounds.
AB  - Two processes are known whereby energy is conserved during substrate metabolism
      in heterotrophic organisms: respiration and fermentation. Both involve oxidation
      reduction reactions; but whereas in respiration the electrons are transferred
      from substrate to an electron acceptor, in fermentation part of the substrate
      molecule itself accepts the electrons. Fermentation is therefore a type of
      disproportionation, and does not involve an overall change in oxidation state of
      the substrate. All fermentative substrates known to date are organic molecules.
      We have discovered a novel type of fermentation involving the disproportionation
      of inorganic sulphur compounds in certain sulphate-reducing bacteria1. Initially
      discovered in a newly isolated sulphate-reducing bacterium, Desulfovibrio
      sulfodismutans, the capacity for disproportionation of sulphur compounds is also
      found in some known sulphate-reducing bacteria and various bacteria isolated from
      freshwater, brackish or marine sediments.

PMID- 22468293
TI  - The use of cough to sample detrusor muscle during flexible cystoscopic biopsy.

PMID- 22468294
TI  - [The surface biomarkers of sputum cells in coal mine workers and patients with
      pneumoconiosis].
AB  - OBJECTIVE: To explore the significance of intercellular adhesion molecule -1
      (CD54 or ICAM-1), epidermal growth factor receptor (EGFR) and platelet-derived
      factor (PDGF) in sputum cells of workers exposed to dust and patients with
      pneumoconiosis for the early diagnosis of pneumoconiosis. METHODS: The subjects
      included 62 workers exposed to dusts, 51 workers not exposed to dusts, 22
      patients with pneumoconiosis and 10 healthy controls. The respiratory sputum
      technique was used to collect the sputum samples and the biomarkers (ICAM-1, EGFR
      and PDGF) of the sputum samples were detected with the sputum samples. RESULTS:
      When the exposure group was compared with non-exposure group, there were no
      significant differences of surface biomarkers (ICAM-1, EGFR and PDGF) in sputum
      cells (neutrophil leucocytes, macrophages, lymphocytes and acidophilic/basophil
      leucocytes). As compared with other workers exposed to dusts, the surface CD54
      and EGFR expression levels increased significantly and the surface PDGF
      expression level decreased significantly in workers exposed to dusts for 10 years
      (P<0.05). As compared with controls, the CD54 and EGFR expression levels of
      sputum cells increased significantly and the PDGF expression level of sputum
      cells decreased significantly in patients with pneumoconiosis at the stages of I
      and II + mI (P<0.05). CONCLUSION: The expression levels of the surface CD54, EGFR
      and PDGF of sputum cells in workers exposed to dusts and patients with
      pneumoconiosis changed, which may be useful for early detecting
      pneumoconiosis.and patients is changed, which may be meaningful for early
      detection of pneumoconiosis.

PMID- 22468295
TI  - [To strength tumour toxicology research due to its huge threat to humans].

PMID- 22468296
TI  - [The analyses on dust pollution of one underground iron mine from 1991 to 2010].
AB  - OBJECTIVE: The main purpose of this work was to give the evidence of reasonable
      and feasible dust control measures which will be taken in the future by analyzing
      the trend of dust concentration from 1991 to 2010 and identifying working faces
      with the severe dust contamination in one underground iron mine. METHODS: The
      data was from routine monitoring between the years 1991 and 2010, which enclosed
      the total dust concentrations and silica contents. China National Standard of
      Occupational exposure limits for hazardous agents in the workplace used to judge
      whether the dust concentration exceeded the National Standard. RESULTS: The
      general trend of total dust concentration from 1991 to 2010 was decreased,
      especially maximum and average levels. The highest exceeding rate was 43.16% in
      1993 and the best years were 2009 and 2010, but the exceeding rates were still
      over 30%. The dust exposure levels varied with different work faces. The mining
      and supporting were the most severe dust pollution faces which the highest ultra
      exceeding rates were 51.61% and 51.48% and the maximum exceeding times were 64.6
      and 16.4 respectively. The next was constructing face with 40.23% exceeding rate
      and 24.6 times more than standard. CONCLUSION: The trend of total dust
      concentration from 1991 to 2010 was decreased, but the dust exceeding rate was
      still high. The strong measures should be taken to control the dust pollution in
      this iron mine, especially mining and supporting faces.

PMID- 22468297
TI  - [Study on acute and subchronic toxicity of ammonium dinitramide].
AB  - OBJECTIVE: To study the acute, subacute and subchronic toxicity induced by
      ammonium dinitramide (ADN), and to ascertain the gradation and target organs of
      acute toxicity induced by AND. METHODS: According to technical specifications for
      toxicity determination of chemicals, the oral tests for acute, subacute and
      subchronic toxicity induced by AND were performed for 90 days. RESULTS: The oral
      LDx for mouse and rat was 568.9 mg/kg and 616.6 mg/kg ADN respectively. The
      gradation of acute toxicity induced by AND was low level. The results of oral
      subacute and subchronic toxicity tests (for 28 and 90 days) showed that a gain in
      weight in group exposed to 123 mg/kg AND was significantly lower than that in
      control group (P<0.05), the TBIL and ALT in group exposed to 61.6 and 123 mg/kg
      AND significantly increased and the ratio of liver weight to body weight
      obviously decreased, as compared with control group, the number of animals with
      hepatic pathological changes in group exposed to 61.6 and 123 mg/kg AND was
      significantly higher than that in control group (P<0.05). CONCLUSION: The
      gradation of acute toxicity induced by ADN was low level. When the exposure dose
      of AND was 30.8 mg/kg, the adverse effect was not observed, and the target organ
      was liver.

PMID- 22468298
TI  - [Analysis on the occupational poisoning case of trichloroethylene reported in
      Dongguan during 2002 to 2009 ].
AB  - OBJECTIVE: To understand the demographic, occupational and clinic characteristics
      of occupational poisoning case due to trichloroethylene in Dongguan in recent
      years for the purpose of prevention. METHODS: Using the trichloroethylene
      patients of poisoning diagnosed in the years between 2002 to 2009 as subjects,
      their age, sex, industry, job, working duration and exposure level were analysed.
      RESULTS: In Dongguan between 2002 and 2009 altogether 82 cases were reported,
      among the 82 cases 8 patients were dead with case fatality rate of 9.8%. among
      them there were 12 cases of poisonings(8 females ,4 males); 9 cases were
      classified as mild poisonings and the rest serious ones, among the 12 cases 3
      patients were dead with case fatality rate of 25.0%; Dermatitis caused by TCE
      there were 70 cases (37 males and 33 females), among the 70 cases 5 patients were
      dead with case fatality rate of 7.1%. 11 persons (91.7%) were engaged in the job
      of cleaning and 1 (8.3%) in water gun, and they performed the job only for 3 days
      in shortest and for 450 days in longest. The cases were distributed in the jobs
      as the following: 29 (41.4%), 12 (17.1%), 8 (11.4%), 5 (7.1%), 4 (5.7%), cases
      respectively in the job of cleaning, parts hanging, board washing, painting, gun
      water spraying; a job duration of 1-50 d (27.4 days in average). CONCLUSION: In
      summary the TCE poisonings in Dongguan were two types of poisoning, i.e.,
      systematic poisonings and drug rash-like dermatitis, occupational TCE poisonings
      took place mainly in the cleaning workers. Dermatitis caused by TCE can cure but
      hard to prevent, we should strengthen the early examination of new works.

PMID- 22468299
TI  - [Study on mutagenicity and teratogenicity of ammonium dinitramide].
AB  - OBJECTIVE: To study the mutagenicity and teratogenicity induced by ammonium
      dinitramide(ADN). METHODS: According to technical specifications for toxicity
      determination of chemicals, Salmonella typhimurium reverse mutation assay (Ames
      assay), in vivo mammalian erythrocyte micronucleus test, sperm malformation test
      and teratogenesis test were used to detect the mutagenicity and teratogenicity
      induced by AND. RESULTS: When the exposure doses of AND were 8-5000 pg/plate, the
      result of Ames assay was negative. As compared with control group, the
      micronucleus rate of mice exposed to 113.8 mg/kg AND significantly
      increased(P<0.05), the sperm malformation rates of mice exposed to 54.4-272.0
      mg/kg AND did not increased significantly. The survival rate of fetuses
      decreased, the rate of assimilated fetuses increased, the rate of fetus sternum
      agenesis enhanced in mice exposed to 319 mg/kg AND, as compared with controls.
      The rates of in the 4th-6th fetus sternum agenesis in groups exposed to 21.3,
      79.7 and 319 mg/kg AND were higher than that in control group. The malformation
      rate of fetus bowels in groups exposed to 319 mg/kg AND was higher than that in
      control group. The teratogenic index of ADN was 30. CONCLUSION: AND may be a
      mutagen and induce the teratogenic effect.

PMID- 22468300
TI  - [Observation of serum superoxide dismutase and glutathione peroxidase activity in
      silica dust exposed workers and silicosis patients].

PMID- 22468301
TI  - [An investigation on the malignancy incidence among rubber industrial workers in
      Hainan province].
AB  - OBJECTIVE: To investigate the malignancy incidence among rubber manufacture and
      preliminary processing industrial workers in Hainan Province of China. METHODS: A
      retrospective survey was conducted on 9 farms in Hainan covering workers who got
      malignant tumor between January 1, 2005 and October 31, 2010. RESULT: On average
      there were 10 320 workers worked on the 9 farms each year. Among them, 167 cases
      of malignancy were found. The morbidity was 279.01 every a hundred thousand and
      standardized morbidity was 159.03 every a hundred thousand; In comparison, we
      also investigated 14228 non-rubber-industry-related workers. 94 malignancy cases
      were found. The morbidity was 113.91 every a hundred thousand and standardized
      morbidity was 64.93 every a hundred thousand. The difference was statistically
      significant (P<0.01) meaning that rubber industrial workers in Hainan Province
      had a higher possibility of getting malignancy. Top 5 types of cancer found in
      this study were lung cancer (17.96%), liver cancer (17.36%), stomach cancer
      (13.17%), rectal cancer and nasopharyngeal carcinoma. 116 cases of these five
      types of cancer took up 69.45% of the total. CONCLUSIONS: Rubber industrial
      workers in Hainan have a higher morbidity of malignancy than other local
      industries. But it is similar to other areas in China.

PMID- 22468302
TI  - [Protective effects of curcumin on vascular endothelial injuries induced by
      radiation].
AB  - OBJECTIVE: To study the effects of curcumin on vascular endothelial injuries
      induced by radiation and the mechanism. METHODS: Human umbilical vein endothelial
      cells (HUVEC) were isolated, cultured and divided into the control group and 4
      groups exposed to 3-ray at the doses of 2, 4, 6 and 8 Gy. Cellular morphological
      and ultrastructural changes were examined under light microscopy and electron
      microscopy respectively. Flow cytometry was used to detect the cellular
      apoptosis, necrosis and intracellular reactive oxygen species(ROS) generation.
      The contents of Lactate dehydrogenase (LDH) and malondialdehyde (MDA) in the
      cultures were measured before and after irradiation. RESULTS: The results of
      cellular morphological and ultrastructural ex-aminations shown that the typical
      apoptotic changes appeared after irradiation. The rates of apoptosis and necrosis
      in groups pretreated with curcumin were significantly lower than those in other
      groups (P<0.05). LDH and MDA in the irradiation groups were significantly higher
      than those in curcumin pretreatment groups (P<0.05). The ROS generation in
      radiation groups significantly increased with the radiation doses, as compared
      with the groups pre-treated with curcumin (P<0.05). CONCLUSION: Irradiation
      induced the apoptosis and necrosis of HUVEC, and increased significantly the
      intracellular LDH and MDA levels in a dose-dependent. Curcumin had the protective
      effects on HUVEC from the apoptosis and necrosis induced by radiation.

PMID- 22468303
TI  - [The curative effect of Fluticasone Salmeterol combined with Tiotropium Bromide
      for silicosis].

PMID- 22468304
TI  - [The image diagnosis of dysbaric osteonecrosis].
AB  - OBJECTIVE: To investigate the imaging features of dysbaric osteonecrosis.
      METHODS: The imaging appearances of four patients with dysbaric osteonecrosis
      caused by diving, were analyzed retrospectively. RESULTS: In four cases with
      dysbaric osteonecrosis including case 1 with stage I, case 2 with stage II, case
      3 and case 4 with stage III, there were a case with the lesion in a bone and
      other 3 cases with lesions in multiple bones,and a case with the lesion in
      unilateral bone and 3 cases with the lesions in lateral bones. (1) The juxta
      articular lesions: there were 10 long bones with the head lesions, including 6
      humerus with the head lesions and 4 femurs with the head lesions in 4 cases. In
      four cases, 10 sclerosis lesions appeared in the heads of long bones, each case
      had a "snow-capped" sclerosis lesion for case 2, case 3 and case 4. There were 7
      small radiolucent lesions and a large radiolucent lesion involved in femur neck.
      The ringlike, linear, bending and punctuate calcification lesions were found on
      CT films of case 2. The osseous collapse in one femur head and the fragmentations
      in three femur heads could be seen in case 3 and case 4; 2 crescent signs can be
      seen in the bilateral femur heads of case 4 with secondary osteoarthritis in left
      hip joint. (2) The diaphyseal and metaphyseal lesions: the X ray film of case 4
      showed the streak and irregular calcifications in the shaft of right humerus;
      there are strip calcifications in diaphyseal and metaphyseal of the left humerus
      on MPR coronal view in case 2. CONCLUSION: The diagnosis of dysbaric
      osteonecrosis suggested that the increased bone density or sclerosis lesions
      appeared in the heads of long bones, and osteonecrosis lesions were found in
      multiple bones or lateral bones.

PMID- 22468305
TI  - [Analysis of 4713 cases of Wuhan pesticide poisoning reports of year 2002 to
      2010].
AB  - OBJECTIVE: To provide scientific evidence of making measures for prevention of
      pesticide poisoning, the investigation on the condition of pesticides poisoning
      was carried out in Wuhan. METHODS: Registration data of pesticide poisoning from
      2002 to 2010 in Wuhan were collected and statistically analyzed by SAS 9.1.
      RESULTS: During the nine years, there were 4713 cases reported for pesticide
      poisoning. Among them, the number of occupational poisoning was 2737 (2 cases
      died), with fatality rate of 0.07%. The number of non-occupational poisoning was
      1976 (159 cases died), and its fatality rate was 8.05%. The incidence of
      occupational poisoning and non-occupational poisoning accounted for 58.1% and
      41.9%, respectively. Insecticides especially organophosphorus insecticides, such
      as parathion, dichlorvos, and methamidophos accounted for 70.6% of the poisoning.
      Occupational poisoning took place mainly in man, accounting for 68.8%, Non
      occupational or life poisoning in contrast mainly occurred in women with a
      proportion of 66.8%. The majority of the occupational poisoning were 30-59 year
      old patients (2239 cases, 81.8%). The majority of the non-occupational poisoning
      were 30-44 year-old patients (665 cases, 33.6%) and - 70 years old patients (209
      cases, 10.6%). High incidence of occupational pesticide poisoning, the regional
      distribution of Caidian (1016 cases, 37.1% ) highest, followed by the Dongxihu,
      Hannan and Huangpi. The pesticide poisoning mainly occurred from July to
      September. The occupational poisoning was mainly caused by poor protection, long
      working hours, and practice not implemented. The non-occupational poisoning was
      mainly caused by suicide. CONCLUSIONS: The majority of the occupational poisoning
      in Wuhan was middle-aged men. The pesticide poisoning was main caused by
      insecticides.

PMID- 22468306
TI  - [Meta-analysis of the effectiveness of plasma exchange in treatment of severe and
      acute organophosphate  poisoning].
AB  - OBJECTIVE: To discuss the effectiveness of severe and acute organophosphate
      poisoning (AOPP) treated with plasma exchange in China. METHODS: Researches about
      effectiveness of severe AOPP treated with plasma exchange were analyzed by Review
      Manager 4.2 and fixed effect model of meta-analysis method were used. RESULTS:
      Six trials including 433 patients were identified. Treatment group including 211
      patients adopted traditional physician therapy plus plasma exchange, and control
      group including 222 patients received physician therapy only. The case-fatality
      rate of the treatment group was lower than the control one [RR=0.30, 95%CI (0.19
      0.49), P<0.01]. CONCLUSION: Plasma exchange can improve the cure rate of severe
      AOPP.

PMID- 22468307
TI  - [Investigation relationship between chronic benzene poisoning and ABO blood
      type].
AB  - OBJECTIVE: To explore the relevance between chronic benzene poisoning and ABO
      blood type. METHODS: 1014 benzene-exposed workers chosen from Shanghai and 4196
      non-benzene-exposed workers chosen from Yangpu district were accepted the ABO
      blood type identification, and two groups of workers compared with the Han
      population of Shanghai and China for the ABO blood type distribution; the 71
      cases of chronic benzene poisoning were compared with the group of benzene
      exposed workers for the ABO blood type distribution. RESULTS: There were no
      significant differences of the ABO blood type distribution among the Han
      population of China, the Han population of Shanghai and the group of non-benzene
      exposed workers (x(2)=7.95, P>0.05). The A type blood distribution frequency in
      the group of chronic benzene poisoning patients was 42.25%, significantly higher
      than the group of benzene-exposed workers (29.48%), and there was statistically
      significant difference (x(2)=5.11,P<0.05). The B type blood distribution
      frequency in the group of chronic benzene poisoning patients was 12.68% ,
      significantly lower than the group of benzene-exposed workers (25.15%), and there
      was statistically significant difference (x(2)=5.61, P<O.05). There were no
      significant differences of the O or AB type blood distribution frequency between
      the group of chronic benzene poisoning patients and the group of benzene-exposed
      workers (P>0.05). CONCLUSION: The people with A type blood are susceptible to
      chronic benzene poisoning, however, the people with B type blood are not
      susceptible to chronic benzene poisoning.

PMID- 22468308
TI  - [Detecting the concentrations of bisphenol A (BPA) in air of workplaces with
      HPLC].
AB  - OBJECTIVE: To establish the method of detecting the concentrations of bisphenol A
      (BPA)in air of workplaces with high performance liquid chromatographic (HPLC).
      METHODS: According to standards of methods for determining the chemical
      substances in workplace air, BPA in the air was collected by glass fiber filter,
      then dissolved by acetonitrile and determined by high performance liquid
      chromatography with FLD. RESULTS: There was a linear relationship within the
      range of 0.01-10.0 pg /ml, and the detection limit was 0.005 pg/ml. The lowest
      detected concentration was 3.3x10-5 mg/m3. The relative standard deviation was
      2.5-5.5%. The dissolution efficiencies were 95.0%-101.9% and the sampling
      efficiencies were 99.6%. The samples in glass fiber filter membrane could be
      stored for 7 days at room temperature. CONCLUSION: The present method could meet
      with the requirements of Guide for establishing occupational health standards
      Part 4 Determination methods of air chemicals in workplace and be feasible for
      determination of BPA in workplace air.

PMID- 22468309
TI  - [Observe effect the treatment of HanFangJiaSu on pneumoconiosis].
AB  - OBJECTIVE: To observe the curative effect of HanFangJiaSu on pneumoconiosis.
      METHOD: 71 patients with silicosis were divided into trial group and control
      group at random. The treating group (36 patients) was treated 90 days with
      HanFangJiaSu and The control group (35 patients) was treated 90 days with
      XiFeiNing. The silicosis with cough,chest complaint, dyspnoea and immune
      modulation were observed before treating and after treating. The effect was
      compared between the two groups. RESULT: To compared with the group before
      treatment and the control group, the symptoms score of cough, chest complaint and
      dyspnoea in treated group was significantly decreased after treatment(P<0.05).
      The rate was decreased by 69.35% in treated group and 50.00% in controls, which
      showed the treatment in both groups was effective. The rate in treated group was
      significantly decreased more than in controls(P<0.05). There were 13 cases with
      respiratory tract infection and 2 cases with lung infection in treated group of
      which percentage were 36.11% and 5.55%, while 22 cases and 4 cases in control
      group of which percentage were 57.14% and 28.57%. There was a significant
      difference between the two groups (P<0.05). To compared with the group before
      treatment, the quantity of CD(4) in blood was obviously increased, while CD(8)
      was obviously decreased, which showed a significant increase of CD(4)/ CD(8),
      (P<0.05). To compared with control group, the quantity of CD(4) in treated group
      was obviously increased, while CD8 was obviously decreased, which also showed a
      significant increase of CD(4)/CD(8) (P<0.05). There was no significant difference
      with the concentration of immune globulin (IgG, IgA, IgM) between the groups
      before and after treatment.

PMID- 22468310
TI  - [Direct determination of 21 elements in serum by dynamic reaction cell
      inductively coupled plasma mass spectrometry].
AB  - OBJECTIVE: To establish a method to directly determine 21 elements in serum by
      dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS).
      METHODS: The serum samples were diluted with 1% nitric acid by 3 times. The
      inductively coupled plasma mass spectrometry (ICP-MS) was used simultaneously to
      detect the serum concentrations of 21 elements (Be, Al, Mn, V, Cr, Fe, Co, Ni,
      Cu, Zn, As, Se, Mo, Ag, Cd, Sb, Ba, T1, Ph, Th, U). RESULTS: The detection limits
      of all elements were between 0.001-0.0711 g/1. Standard linear correlation
      coefficients (r) were 50.999. Standard deviations were less than 5%,the recovery
      rates were 90%-114%. Standard reference materials were used for quality control
      standards and the analysis results conformed with the certified values.
      CONCLUSION: The present method is a simple, rapid,sensitive and accurate method
      for detecting the serum samples.

PMID- 22468311
TI  - [Determination of carbon tetrachloride in the workplace air with chromatography].

PMID- 22468312
TI  - [The therapeutic effects of treatment by HanFangJiaSu with pill of six
      ingredients with  rehmannia on 56 cases of silicosis patients].

PMID- 22468313
TI  - [Detecting the nitrogen oxide in air with portable infrared spectrometer].
AB  - OBJECTIVE: To establish a method for rapid detecting nitric oxide (NO) and
      nitrogen dioxide(NO2) in the workplace air with infrared spectrometer. METHODS:
      The method of infrared spectrometer was developed to detect nitrogen oxide in
      laboratory, then applied to detect the concentration of nitrogen oxide in
      workplace air. The present method was compared with National Standard Methods.
      RESULTS: NO and NO2 in air were detected simultaneously with the infrared
      spectrometer, not interfering each other. In standard condition, the minimum
      detectable concentrations of NO and NO2 were 0.67 and 1.03 mg/m3, the inferior
      limits of concentrations were 0.67 and 1.03 mg/m3 respectively. When the
      concentrations of NO and NO2 were 0.67-133.93 mg/m3 and 1.03-102.68 mg/m3, the
      accuracy and precision of detection were higher. As compared with National
      Standard Methods, the ratio of the results of two methods was 86.96% and 112.56%.
      CONCLUSION: The method of infrared spectrometer is a rapid, simple and accurate
      method for detecting the concentrations of nitrogen oxide in the workplace air.

PMID- 22468314
TI  - [Clinical observation on children-sized fibreoptic bronchoscope usage in whole
      lung lavage].
AB  - OBJECTIVE: To explore the effect of children-sized fibreoptic bronchoscope in
      improving the safety of whole-lung lavage (WLL). METHOD: Patients from May 2006
      to May 2010 using children-sized fibreoptic bronchoscope to assistant the
      location were assigned to fibreoptic bronchoscope group. Patients from May 1998
      to Nov 2004 using traditional stethoscope to help intubation were assigned to
      control group. The adverse reactions and complications were compared. RESULT:
      There were liquid leakage 1 case (0.96%), hypoxia 3 cases (2.88%) and liquid
      retained over 1000 ml 15 cases (14.42%) in fibreoptic bronchoscope group. In
      contrast, liquid leakage 24 cases (6.38%), hypoxia 42 cases (11.17%) and liquid
      retained over 1000 ml 135 cases (35.90%) happened in control group. The
      differences between the two groups were significant (P<0.05, P<0.01). CONCLUSION:
      Using children-sized fibreoptic bronchoscope in WLL can promote the situation of
      double-lumen tube, help separation the two lungs, decrease complications and
      improving safety.

PMID- 22468315
TI  - [Improvement on flame atomic absorption spectrometry for determining Tin
      concentration in air of workplaces].
AB  - OBJECTIVE: To explore the influence factors on determining Tin concentration in
      air of workplaces with flame atomic absorption spectrometry and to establish an
      accurate, sensitive and high-efficient method. METHODS: The different reagents
      were used to digest the sampling filter membranes and the determining conditions
      of flame atomic absorption spectrometry were adjusted, then the determining
      results were compared. RESULTS: When 3 ml hydrochloric acid and 0.5 ml nitric
      acid served as the digesting reagents and the determining conditions of flame
      atomic absorption spectrometry were adjusted to the best conditions, there was
      the good linearity in the tested concentration range of Tin, the correlation
      coefficient was larger than 0.9990. The limit of quantification was 1.0 p.g/ml.
      The extraction recovery was between 99.6%-102.6%, and the RSD were all less than
      5.0%. CONCLUSION: The proper kinds and quantity of digestive reagents in
      pretreatment of the samples should be chosen for the accuracy and precision of
      the determination according to the influence factors of determination.

PMID- 22468316
TI  - [The curative effect observation of two kinds of lung lavage in pneumoconiosis].

PMID- 22468317
TI  - [Dynamic change study of dermatitis medicamentosa-like of trichloroethylene
      patients with liver damage].
AB  - OBJECTIVE: Observing the dynamic change characteristics of serum liver function
      indexes in occupational dermatitis medicamentosa-like of trichloroethylene
      patients with liver damage, we can underlie for guiding therapy, prognosis and
      mechanism of dermatitis medicamentosa-like of trichloroethylene patients with
      liver damage. METHODS: We collected serum of 10 cases of occupational dermatitis
      medicamentosa-like of trichloro-ethylene patients with liver damage from
      different time points since they were hospitalized, using automatic biochemistry
      analyzer to detect total protein (TP), albumin (ALB), total bilirubin (TBIL),
      direct bilirubin (DBIL), indirect bilirubin (IBIL), alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT),
      alkaline phosphatase (ALP), albumin/globulin ratio etc 11 liver function
      biochemical indicators. We used Excel to establish database, professional drawing
      software gnuplot to draw dynamic variation diagram of each index. RESULTS: The
      variation range of 11 liver function indexes of 10 cases was TP 43.2-74.2 g/L,
      ALB 24.6-44.6 g/L, A/G 0.77-2.10, TBIL 3.7-268.2 umol/L, DBIL 1.0-166.0 umol/L,
      IBIL 2.4 -167.5 umol/L, ALT 11-5985 U/L, AST 14-5586 U/L, GGT 15-1500 U/L, ALP 35
      309 U/L, S/L 0.07-1.94, respectively. TBIL, DBIL, ALT, AST, GGT, ALP
      concentration significantly increased, especially ALT, AST, GGT, ALT topped 5985
      U/L, AST topped 5586 U/L, GGT topped 1500 U/L. But TP, ALB and S/L significantly
      decreased, TP lowest to 43.2 g/L, S/L lowest to 0.07. A/G basically remained
      unchanged, but IBIL didn't change regularly. CONCLUSION: The early liver damage
      in dermatitis medicamentosa-like of trichloroethylene patients was serious, and
      repeatedly attacked, so we should lead to enough attention to the clinical work
      and prevention. This also provided the basis for studying the mechanism of
      trichloroethylene poisoning.

PMID- 22468318
TI  - [Evaluating the uncertainty in urinary fluoride measurement by ion selective
      electrode method].
AB  - OBJECTIVE: To evaluate the uncertainty of measurement result of urinary fluoride
      and to provide quality assurance for determinations. METHOD: The investigation
      was conducted, according with principles and methods for uncertainty evaluation.
      RESULTS: The uncertainty of the combined standard of present method was 2.86 %.
      For the sample containing 4.47 mg/L urinary fluoride, the expanded uncertainty
      was 0.26 mg/L. CONCLUSION: The uncertainty of the present method was mainly from
      the sample repeatability, the preparation of standard solution, the linearity of
      the calibration curve and instruments and so on.

PMID- 22468319
TI  - [An accident of hydrogen sulfide poisoning].

PMID- 22468320
TI  - [Evaluating personal protective measures in occupational hazards assessment].

PMID- 22468321
TI  - [Clinical application of therapeutic lung lavage].

PMID- 22468322
TI  - Position-specific carbon isotope analysis of trichloroacetic acid by gas
      chromatography/isotope ratio mass spectrometry.
AB  - Trichloroacetic acid (TCAA) is an important environmental contaminant present in
      soils, water and plants. A method for determining the carbon isotope signature of
      the trichloromethyl position in TCAA using gas chromatography/combustion/isotope
      ratio mass spectrometry (GC/C/IRMS) was developed and tested with TCAA from
      different origins. Position-specific isotope analysis (PSIA) can provide direct
      information on the kinetic isotope effect for isotope substitution at a specific
      position in the molecule and/or help to distinguish different sources of a
      compound. The method is based on the degradation of TCAA into chloroform (CF) and
      CO2 by thermal decarboxylation. Since thermal decarboxylation is associated with
      strong carbon isotope fractionation (epsilon = -34.6 +/- 0.20/00) the reaction
      conditions were optimized to ensure full conversion. The combined isotope ratio
      of CF and CO2 at the end of the reaction corresponded well to the isotope ratio
      of TCAA, confirming the reliability of the method. A method quantification limit
      (MQL) for TCAA of 18.6 ug/L was determined. Samples of TCAA produced by enzymatic
      and non-enzymatic chlorination of natural organic matter (NOM) and some
      industrially produced TCAA were used as exemplary sources. Significant different
      PSIA isotope ratios were observed between industrial TCAA and TCAA samples
      produced by chlorination of NOM. This highlights the potential of the method to
      study the origin and the fate of TCAA in the environment.

PMID- 22468323
TI  - A discharge adaptor interface for use in liquid chromatography/mass spectrometry.
AB  - A discharge adaptor, composed of a metal casing and platinum (Pt) wire needle,
      was directly attached to an electrospray ionization (ESI) probe tip, to transform
      the ionization into atmospheric pressure chemical ionization (APCI). Six generic
      drugs were analyzed with the developed discharge adaptor (DA) and two commercial
      interfaces. The DA interface produced more intense radical anions, [M]-, and less
      sodium adduct ions, [M + Na]+, than the ESI interface, whereas almost the same
      molecular ions were detected as the APCI interface. The effects of solvent and
      desolvation gas flow in the DA interface were similar to those in the ESI
      interface, but differed from those in the APCI interface. Better sensitivity of
      the tested drugs was obtained relative to the commercial APCI interface. For
      human plasma samples, the DA interface also demonstrated good tolerance to plasma
      matrices, linearity from 5 or 20 to 500 ng/mL (r2 > 0.99) and ruggedness.

PMID- 22468324
TI  - Biodegradability screening of soil amendments through coupling of wavelength
      scanned cavity ring-down spectroscopy to multiple dynamic chambers.
AB  - A system was developed for the automatic measurements of 13CO2 efflux to
      determine biodegradation of extra carbon amendments to soils. The system combines
      wavelength-scanned cavity ring down laser spectroscopy (WS-CRDS) with the open
      dynamic chamber (ODC) method. The WS-CRDS instrument and a batch of 24 ODC are
      coupled via microprocessor-controlled valves. Determination of the biodegradation
      requires a known delta13C value and the applied mass of the carbon compounds, and
      the biodegradation is calculated based on the 13CO2 mixing ratio (ppm) sampled
      from the headspace of the chambers. The WS-CRDS system provided accurate
      detection based on parallel samples of three standard gases (13CO2 of 2, 11 and
      22 ppm) that were measured simultaneously by isotope ratio mass spectrometry
      (linear regression R2 = 0.99). Repeated checking with the same standards showed
      that the WS-CRDS system showed no drift over seven months.The applicability of
      the ODC was checked against the closed static chamber (CSC) method using the
      rapid biodegradation of cane sugar-delta13C-labeled through C4 photosynthesis.
      There was no significant difference between the results from 7-min ODC and 120
      min CSC measurements. Further, a test using samples of either cane sugar (C4) or
      beetroot sugar (C3) mixed into standard soil proved the target functionality of
      the system, which is to identify the biodegradation of carbon sources with
      significantly different isotopic signatures.

PMID- 22468325
TI  - Continuous analysis of delta18O and deltaD values of water by diffusion sampling
      cavity ring-down spectrometry: a novel sampling device for unattended field
      monitoring of precipitation, ground and surface waters.
AB  - A novel sampling device suitable for continuous, unattended field monitoring of
      rapid isotopic changes in environmental waters is described. The device utilises
      diffusion through porous PTFE tubing to deliver water vapour continuously from a
      liquid water source for analysis of delta18O and deltaD values by Cavity Ring
      Down Spectrometry (CRDS). Separation of the analysed water vapour from non
      volatile dissolved and particulate contaminants in the liquid sample minimises
      spectral interferences associated with CRDS analyses of many aqueous samples.
      Comparison of isotopic data for a range of water samples analysed by Diffusion
      Sampling-CRDS (DS-CRDS) and Isotope Ratio Mass Spectrometry (IRMS) shows
      significant linear correlations between the two methods allowing for accurate
      standardisation of DS-CRDS data. The internal precision for an integration period
      of 3 min (standard deviation (SD) = 0.10/00 and 0.30/00 for delta18O and deltaD
      values, respectively) is similar to analysis of water by CRDS using an
      autosampler to inject and evaporate discrete water samples. The isotopic effects
      of variable air temperature, water vapour concentration, water pumping rate and
      dissolved organic content were found to be either negligible or correctable by
      analysis of water standards. The DS-CRDS system was used to analyse the O and H
      isotope composition in short-lived rain events. Other applications where finely
      time resolved water isotope data may be of benefit include recharge/discharge in
      groundwater/river systems and infiltration-related changes in cave drip water.

PMID- 22468326
TI  - Molecular histology analysis by matrix-assisted laser desorption/ionization
      imaging mass spectrometry using gold nanoparticles as matrix.
AB  - Gold nanoparticles (AuNPs) were applied and optimized as matrix for matrix
      assisted laser desorption/ionization mass spectrometry analysis of animal
      tissues, and enabled histological analysis of animal tissues at molecular level
      by imaging mass spectrometry (IMS). AuNPs were coated on animal tissue in a
      solvent-free manner via argon ion sputtering. Metabolites, including
      neurotransmitters, fatty acids and nucleobases, were directly detected from mouse
      brain tissue. Based on region-specific chemical profiles, fine histological
      features of mouse brain tissue and heterogeneous regions of tumor tissue were
      both revealed.

PMID- 22468327
TI  - Consistent predictable patterns in the hydrogen and oxygen stable isotope ratios
      of animal proteins consumed by modern humans in the USA.
AB  - Published datasets of proteinaceous animal tissues suggest that co-variation
      between amino acid hydrogen (delta2H) and oxygen (delta18O) isotope ratios is a
      common feature in systems where isotopic variation is driven by geographic or
      temporal variation in the delta2H and delta18O values of environmental water.
      This has led to the development of models relating tissue delta2H and delta18O
      values to those of water, with potential application in a number of fields.
      However, the strength and ubiquity of the influence of environmental water on
      protein isotope ratios across taxonomic groups, and thus the relevance of
      predictive models, is an open question. Here we report strong co-variation of
      delta2H and delta18O values across a suite of terrestrial and aquatic animal
      meats purchased in American food markets, including beef, poultry (chicken and
      turkey), chicken eggs, pork, lamb, freshwater fish, and marine fish. Significant
      isotope co-variation was not found for small collections of marine bivalves and
      crustaceans. These results imply that isotopic signals from environmental water
      were propagated similarly through most of the diverse natural and human-managed
      foodwebs represented by our samples. Freshwater fish had the largest variation in
      delta2H and delta18O values, with ranges of 1210/00 and 19.20/00, respectively,
      reflecting the large isotopic variation in environmental freshwaters. In contrast
      marine animals had the smallest variation for both delta2H (70/00 range,
      crustaceans) and delta18O (3.00/00 range, bivalves) values. Known-origin beef
      samples demonstrated direct relationships between the variance of environmental
      water isotope ratios and that of collected meats.

PMID- 22468328
TI  - delta18O values of Sus scrofa blood water and bone phosphate; a marked
      discrepancy between domestic and wild specimens.
AB  - delta18O analyses of water in the blood of domestic and wild pigs indicated that
      large isotopic differences exist between domestic and wild specimens of the same
      species (Sus scrofa) living in the same area. Similar isotopic differences are
      found between the delta18O(PO43-) values of bones from the two groups of animals.
      When delta18O values obtained from recent wild boar bones are introduced in the
      equation of the isotopic scale determined for domestic pigs, totally unreliable
      delta18O values of local meteoric water are obtained. The delta18O(PO43-) values
      measured in three groups of modern wild boar specimens allow the calculation of a
      first approximate equation which is quite different from that of domestic pigs.
      This isotopic scale should be accurately re-calibrated for wild animals.

PMID- 22468329
TI  - Stable isotopic analysis of pyrogenic organic matter in soils by liquid
      chromatography-isotope-ratio mass spectrometry of benzene polycarboxylic acids.
AB  - Pyrogenic organic matter (PyOM), the incomplete combustion product of organic
      materials, is considered stable in soils and represents a potentially important
      terrestrial sink for atmospheric carbon dioxide. One well-established method of
      measuring PyOM in the environment is as benzene polycarboxylic acids (BPCAs), a
      compound-specific method, which allows both qualitative and quantitative
      estimation of PyOM. Until now, stable isotope measurement of PyOM carbon involved
      measurement of the trimethylsilyl (TMS) or methyl (Me) polycarboxylic acid
      derivatives by gas chromatography-combustion-isotope ratio mass spectrometry (GC
      C-IRMS). However, BPCA derivatives can contain as much as 150% derivative carbon,
      necessitating post-analysis correction for the accurate measurement of delta13C
      values, leading to increased measurement error. Here, we describe a method for
      delta13C isotope ratio measurement and quantification of BPCAs from soil-derived
      PyOM, based on ion-exchange chromatography (IEC-IRMS). The reproducibility of the
      delta13C measurement of individual BPCAs by IEC-IRMS was better than 0.350/00
      (1sigma). The delta13C-BPCA analysis of PyOM in soils, including at natural and
      artificially enriched 13C-abundance, produced accurate and precise delta13C
      measurements. Analysis of samples that differed in delta13C by as much as 9000/00
      revealed carryover of <10/00 between samples. The weighted sum of individual
      delta13C-BPCA measurements was correlated with previous isotopic measurements of
      whole PyOM, providing complementary information for bulk isotopic measurements.
      We discuss potential applications of delta13C-BPCA measurements, including the
      study of turnover rates of PyOM in soils and the partitioning of PyOM sources
      based on photosynthetic pathways.

PMID- 22468330
TI  - Does natural weathering change the stable isotope composition (2H, 13C, 15N, 18O
      and 34S) of cattle hair?
AB  - Stable isotope analysis of hair has found applications in many fields of science
      because it provides a temporally resolved, fairly stable isotopic archive of
      mammalian individuals. We investigated whether this hair archive is modified by
      natural weathering while attached to a living animal. We analyzed the tail switch
      hairs of one suckler cow, sampled seven times over a period of four annual summer
      pasture-winter stall feeding cycles. We compared relative isotope ratios
      (delta2H, delta13C, delta15N, delta18O and delta34S) of sections of hair that
      grew simultaneously but were exposed to natural weathering conditions over
      different periods of time. Natural wear caused a loss of mass of approx. 0.13%
      day-1, with no apparent effect of environmental conditions. Changes in delta2H,
      delta13C, delta15N and delta18O were below the detection limit, indicating that
      hair is a reliable archive for the isotopes of these elements. In contrast,
      delta34S values increased during the grazing period by about 10/00, with exposure
      to UV radiation appearing to have a major influence on this result. The delta34S
      values decreased during the subsequent stall period, probably due to abrasion.
      Seasonal variation in delta34S may indicate alternating environments that differ
      in their weathering conditions.

PMID- 22468331
TI  - Combining transmission geometry laser ablation and a noncontact continuous flow
      surface sampling probe/electrospray emitter for mass spectrometry based chemical
      imaging.
AB  - This paper describes the coupling of ambient pressure transmission geometry laser
      ablation with a liquid-phase sample collection into a continuous flow surface
      sampling probe/electrospray emitter for mass spectrometry based chemical imaging.
      The flow probe/emitter device was placed in close proximity to the surface to
      collect the sample plume produced by laser ablation. The sample collected was
      immediately aspirated into the probe and onto the electrospray emitter, ionized
      and detected with the mass spectrometer. Freehand drawn ink lines and letters and
      an inked fingerprint on microscope slides were analyzed. The circular laser
      ablation area was about 210 um in diameter and under the conditions used in these
      experiments the spatial resolution, as determined by the size of the surface
      features distinguished in the chemical images, was about 100 um.

PMID- 22468332
TI  - Towards a full reference library of MS(n) spectra. II: A perspective from the
      library of pesticide spectra extracted from the literature/Internet.
AB  - To gain perspective on building full transferable libraries of MS(n) spectra from
      their diverse/numerous collections, a new library was built from 1723 MS(>1)
      spectra (mainly MS2 spectra) of 490 pesticides and related compounds. Spectra
      acquired on different types of tandem instruments in various experimental
      conditions were extracted from 168 literature articles and Internet sites.
      Testing of the library was based on searches where 'unknown' and reference
      spectra originated from different sources (mainly from different laboratories)
      were cross-compared. The NIST 05 MS2 library was added to the reference spectra.
      The library searches were performed with all the test spectra or were divided
      into different subsamples containing (a) various numbers of replicate spectra of
      test compounds or (b) spectra acquired from different instrument types. Thus, the
      dependence of true/false search (identification) result rates on different
      factors was explored. The percentage of 1st rank correct identifications (true
      positives) for the only 'unknown' mass spectrum and two and more reference
      spectra and matching precursor ion m/z values was 89%. For qualified matches,
      above the cut-off match factor, that rate decreased to 80%. The corresponding
      rates based on the best match for two and more 'unknown' and reference spectral
      replicates were 89-94%. For quadrupole instruments, the rates were even higher:
      91-95% (one 'unknown' spectrum) and 90-100% (two and more such spectra). This
      study shows that MS2 spectral libraries generated from the numerous
      literature/Internet sources are not less efficient for the goal of identification
      of unknown compounds including pesticides than very common EI-MS1 libraries and
      are almost as efficient as the most productive from current MS2 spectral
      databases. Such libraries may be used as individual reference databases or
      supplements to large experimental spectral collections covering many groups of
      abundant compounds and different types of tandem mass spectrometers.

PMID- 22468333
TI  - Systematic evaluation of acetone and acetonitrile for use in hydrophilic
      interaction liquid chromatography coupled with electrospray ionization mass
      spectrometry of basic small molecules.
AB  - Sub-2-um particle size hydrophilic interaction liquid chromatography [HILIC]
      combined with mass spectrometry has been increasing in popularity as a
      complementary technique to reversed-phase LC for the analysis of polar analytes.
      The organic-rich mobile phase associated with HILIC techniques provides increases
      in compound ionization, due to increased desolvation efficiency during
      electrospray ionisation mass spectrometric (ESI-MS) analysis. Although recent
      publications illustrated selectivity and response comparisons between reversed
      phase LC/MS and HILIC LC/MS, there are limited discussions evaluating the
      optimisation of the mass spectrometry parameters regarding analytes and
      alternative mobile phases. The use of acetone as an alternative organic modifier
      in HILIC has been investigated with respect to signal-to-noise in ESI-MS for a
      variety of polar analytes. Analyte reponses were measured based on a variety of
      cone and capillary voltages at low and high pH in both acetone and acetonitrile.
      In order to visualise compound behaviour in the ESI source, surface plots were
      constructed to assist in interpreting the observed results. The use of acetone in
      ESI is complicated at low m/z due to the formation of condensation products.
      Favourable responses were observed for certain analytes and we envisage offering
      an insight into the use of acetone as an alternative to acetonitrile under
      certain analytical conditions for particular compound classifications for small
      molecule analysis. We also highlight the importance of optimising source voltages
      in order to obtain the maximum signal stability and sensitivity, which are
      invariably, highly solvent composition dependent parameters.

PMID- 22468334
TI  - The Center for Medical Education and Innovation at Riverside.

PMID- 22468335
TI  - Prebiotics and probiotics: methodology, efficacy, and potential health
      considerations.

PMID- 22468336
TI  - Prebiotics and probiotics: some thoughts on demonstration of efficacy within the
      regulatory sphere.
AB  - Probiotics and prebiotics present regulators with challenges because they require
      a demonstrated positive health outcome and proof that the prebiotic or probiotic
      is the agent of action once safety aspects have been satisfied. Thus, probiotic
      and prebiotic definitions are important because they will set the criteria by
      which these materials will be judged within the regulatory sphere. Use of the
      terms probiotic and prebiotic are, themselves, considered health claims in some
      jurisdictions, so that both product health claims and product content labeling
      may be regulated. Currently accepted definitions of prebiotic and probiotic make
      it easier to draw a straight line between ingestion and health outcome for
      probiotics but much more difficult for prebiotics, where a health outcome must be
      linked to changes in specific bacterial species within the gut microbial
      community. These challenges highlight the difficulties facing regulatory bodies
      and the scientific community when emerging science is turned into consumable
      product.

PMID- 22468337
TI  - Molecular methods to measure intestinal bacteria: a review.
AB  - The intestine is an exceptionally rich ecosystem encompassing a complex
      interaction among microorganisms, influenced by host factors, ingested food, and
      liquid. Characterizing the intestinal microbiota is currently an active area of
      research. Various molecular-based methods are available to characterize the
      intestinal microbiota, but all methods possess relative strengths, as well as
      salient weaknesses. It is important that researchers are cognizant of the
      limitations of these methods, and that they take the appropriate steps to
      mitigate weaknesses. Here, we discuss methodologies used to monitor intestinal
      bacteria including: (i) traditional clone libraries; (ii) direct sequencing using
      next-generation parallel sequencing technology; (iii) denaturing gradient gel
      electrophoresis and temperature gradient gel electrophoresis; (iv) terminal
      restriction fragment length polymorphism analysis; (v) fluorescent in situ
      hybridization; and (vi) quantitative PCR. In addition, we also discuss
      experimental design, sample collection and storage, DNA extraction, gene targets,
      PCR bias, and methods to reduce PCR bias.

PMID- 22468338
TI  - Gut microbiota, diet, and heart disease.
AB  - Modulation of the gut microbiota is an area of growing interest, particularly for
      its link to improving and maintaining the systemic health of the host. It has
      been suggested to have potential to reduce risk factors associated with chronic
      diseases, such as elevated cholesterol levels in coronary heart disease (CHD).
      Diets of our evolutionary ancestors were largely based on plant foods, high in
      dietary fiber and fermentable substrate, and our gut microbiota has evolved
      against a background of such diets. Therapeutic diets that mimic plant-based
      diets from the early phases of human evolution may result in drug-like
      cholesterol reductions. In contrast, typical Western diets low in dietary fiber
      and fermentable substrate, and high in saturated and trans fatty acids, are
      likely contributors to the increased need for pharmacological agents for
      cholesterol reduction. The gut microbiota of those consuming a Western diet are
      likely underutilized and depleted of metabolic fuels, resulting in a less than
      optimal gut microbial profile. As a result, this diet is mismatched to our
      archaic gut microbiota and, therefore, to our genome, which has changed
      relatively little since humans first appeared. While the exact mechanism by which
      the gut microbiota may modulate cholesterol levels still remains uncertain, end
      products of bacterial fermentation, particularly the short chain fatty acids
      (i.e., propionate), have been suggested as potential candidates. While more
      research is required to clarify the potential link between gut microbiota and CHD
      risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber,
      and fermentable substrate would be a useful strategy for improving systemic
      health, possibly by altering the gut microbiota.

PMID- 22468339
TI  - Probiotic and prebiotic applications for vaginal health.
AB  - Infections of the urogenital tract in women are extremely common, and there is no
      evidence of a reduction in incidence. Treatment and preventive strategies have
      been relatively unchanged for 50 years. The concept of using probiotic
      lactobacilli or prebiotics that stimulate the growth of protective organisms
      emerged in the mid-1980s and has led to several strains being tested successfully
      in women. With the advent of genomic profiling of the healthy vaginal microbiota,
      an improved understanding of metabolic systems within lactobacilli, and the
      ability to deliver products in food and supplement forms, the future should see
      new ways for women to restore and maintain their vaginal health, without the side
      effects of pharmaceutical agents. Indeed, studies indicate that probiotics can be
      taken in conjunction with the antibiotics and antifungal agents used to eradicate
      infections. In the future, probiotics and prebiotics will represent an important
      adjunct to pharmaceutical and other approaches used to care for feminine health.

PMID- 22468340
TI  - Immunological responses to gut bacteria.
AB  - The integral nature of interactions between the gut microbiota and host is
      especially evident with respect to effects on the immune system and host
      defenses. Host-microbiota interactions are increasingly being revealed as complex
      and dynamic, with far-reaching effects on varied aspects of host health. This
      review focuses on adaptive and innate immune responses to the gut microbiota and
      the bidirectional nature of these host-microbe interactions.

PMID- 22468341
TI  - Bacteria, colonic fermentation, and gastrointestinal health.
AB  - The colonic microbiota plays an important role in human digestive physiology and
      makes a significant contribution to homeostasis in the large bowel. The
      microbiome probably comprises thousands of different bacterial species. The
      principal metabolic activities of colonic microorganisms are associated with
      carbohydrate and protein digestion. Nutrients of dietary and host origin support
      the growth of intestinal organisms. Short-chain fatty acids (SCFAs),
      predominantly acetate, propionate, and butyrate, are the principal metabolites
      generated during the catabolism of carbohydrates and proteins. In contrast,
      protein digestion yields a greater diversity of end products, including SCFAs,
      amines, phenols, indoles, thiols, CO2, H2, and H2S, many of which have toxic
      properties. The majority of SCFAs are absorbed from the gut and metabolized in
      various body tissues, making a relatively small but significant contribution to
      the body's daily energy requirements. Carbohydrate fermentation is, for the most
      part, a beneficial process in the large gut, because the growth of saccharolytic
      bacteria stimulates their requirements for toxic products associated with
      putrefaction, for incorporation into cellular proteins, thereby protecting the
      host. However, as digestive materials move along the gut, carbohydrates become
      depleted, which may be linked to the increased prevalence of colonic disease in
      the distal bowel.

PMID- 22468342
TI  - Interlaboratory comparison of an analytical method for the determination of
      semduramicin in poultry feed at the authorized level using high-performance
      liquid chromatography coupled to postcolumn derivatization and spectrophotometric
      detection.
AB  - The performance characteristics of a method based on HPLC with postcolumn
      derivatization and spectrophotometric detection for the quantification of
      semduramicin in poultry feedingstuffs have been determined via a collaborative
      study. Semduramicin is a feed additive that is authorized for fattening chickens
      within the European Union at a minimum and maximum content of 20 and 25 mg/kg in
      feedingstuffs, respectively. The target concentration of semduramicin in the test
      samples ranged from 11.5 to 45.0 mg/kg. The study has been conducted with two
      different types of test material, namely, feedingstuff samples that have been
      previously ground in our laboratory and pelleted feedingstuffs. In the latter
      case, the laboratories participating in the study had to grind the samples prior
      to analysis. The obtained RSD for repeatability (RSD(r)) ranged from 2 to 10% for
      the ground materials, and from 2 and 7% for the pelleted materials. The RSD for
      reproducibility (RSDR) varied between 11 and 16% for the ground materials, and
      between 12 and 15% for the pelleted materials. These data indicated that grinding
      as an additional step in the analytical procedure did not influence the precision
      profile of the method. In addition, the HorRat values for all test materials were
      below or equal to 1.5, thus demonstrating that the obtained precision data were
      acceptable for the purpose of the method. Furthermore, an estimation of trueness
      based on statistical treatment of the results reported from the laboratories for
      spiked samples revealed acceptable mean recovery values of 88 +/- 4%. Based on
      the obtained performance profile, the method can be considered fully validated
      and transferable to control laboratories to be used within the framework of
      official control.

PMID- 22468343
TI  - Differentiating the gum resins of two closely related Indian Gardenia species, G.
      gummifera and G. lucida, and establishing the source of dikamali gum resin using
      high-performance thin-layer chromatography and ultra-performance liquid
      chromatography-UV/MS.
AB  - Dikamali is a gum resin obtained from the leaf buds of Gardenia lucida or G.
      gummifera. There is controversy regarding the botanical source of this gum resin
      with some stating it to be from G. lucida while others claim it to be from G.
      gummifera. Analytical methods including UPLC and HPTLC were developed for the
      qualitative analysis of Gardenia species and various commercial samples. The
      separation using a UPLC method was achieved within 12.0 min by using C18 column
      material, a water/acetonitrile mobile phase, both containing formic acid, a
      gradient system, and a temperature of 40 degrees C. Extensive studies of dikamali
      collected from various parts of India in comparison with the gum resins collected
      from G. lucida and G. gummifera clearly indicated that the botanical source of
      commercially available dikamali is G. lucida, not G. gummifera. The marker
      compounds isolated from a market sample of dikamali were present only in the gum
      resin of G. lucida and the compounds isolated from G. gummifera were not present
      in any of the dikamali samples, confirming the botanical source of dikamali. This
      work is of utmost importance, given the ambiguity regarding the botanical source
      of the gum resin dikamali. LC/MS coupled with electrospray ionization is
      described for the identification and confirmation of nine compounds from various
      samples of the gum resin. An HPTLC method was also developed for the fast
      chemical fingerprint analysis of Gardenia samples.

PMID- 22468344
TI  - Development and validation of rapid ion-pair RPLC method for simultaneous
      determination of certain B-complex vitamins along with vitamin C.
AB  - A rapid, simple, and accurate ion-pair RPLC method has been developed for
      simultaneous analysis of vitamin C and major B-complex vitamins. An RP C18 column
      thermostated at 30 degrees C was used with gradient elution of mobile phase
      comprising 10 mM potassium dihydrogen phosphate buffer (containing 3 mM sodium
      hexane-1-sulfonate, adjusted to pH 2.80 with o-phosphoric acid) and methanol at a
      flow rate of 1.0 mL/min to achieve the best possible separation and resolution of
      all vitamins in about 11.00 min. The detection was performed at 274 nm. The
      method has been implemented successfully for simultaneous determination of
      vitamins present in 12 multivitamin/multimineral pharmaceutical preparations, as
      well as in human urine. Typical validation characteristics were evaluated in
      accordance with International Conference on Harmonization guidelines. Good
      linearity over the investigated concentration levels was observed. Intraday
      repeatability was < or = 2.0%, and interday variation was < or = 2.6%, for all
      vitamins. The method can be used for assay of these vitamins over a wide
      concentration range with good precision and accuracy; hence, it would be
      appropriate for routine QC as well as in clinical analysis.

PMID- 22468345
TI  - Quantitative HPLC method for determining two of the major active phthalides from
      Ligusticum porteri roots.
AB  - Z-Ligustilide (1) and Z-6,6',7,3'-alpha-diligustilide (2), two of the major
      active phthalides of the medicinal plant Ligusticum porteri (osha), were chosen
      for the development and validation of an HPLC-diode array detection method
      suitable for QC of the crude drug. The method used gradient elution to achieve
      separation on a Hibar RT LiChrospher 100 C18 column. The LOD values were 29 and
      45 microg/mL, and the LOQs were 89 and 125 microg/mL, respectively. The method
      showed good intraday precision (%RSD: 0.7 for 1 and 3.1 for 2) and interday
      precision (%RSD: 1.2 for 1 and 1.8 for 2). The method was used for the analysis
      of 1 and 2 in crude drug samples and several herbal preparations from Mexico and
      the United States. Quantitative analysis showed that the content of the two
      phthalides varied significantly among the samples. All the samples contained
      higher concentrations of 1 (0.15-2.5%) than 2 (0.002-1.0%). The profiles of
      volatile compounds in the essential oil obtained by hydrodistillation and solid
      phase microextraction of L. porteri roots were analyzed by GC-MS. Thirty one
      chemical constituents (> 99.7% of the total content) were identified in the
      essential oil, which was characterized by the presence of a high percentage of
      phthalides (44.61%) and sesquiterpenes (10.69%). The major light volatile
      components extracted by solid-phase microextraction were monoterpenes.

PMID- 22468346
TI  - BIOTECON diagnostics foodproof Listeria monocytogenes Detection Kit, 5' nuclease
      in combination with the foodproof ShortPrep II Kit.
AB  - A method was developed for the detection of Listeria monocytogenes in food. The
      method is based on real-time PCR using hydrolysis probes (5' Nuclease). This
      advanced PCR method was designed to reduce the time necessary to achieve results
      from PCR reactions and to enable the user to monitor the amplification of the PCR
      product simultaneously, in real-time. After DNA isolation using the BIOTECON
      foodproof ShortPrep II Kit designed for the rapid preparation of L. monocytogenes
      DNA for direct use in PCR, the real-time detection of L. monocytogenes DNA is
      carried out using the foodproof Listeria monocytogenes Detection Kit. The kit
      provides primers and hydrolysis probes for sequence-specific detection,
      convenient premixed reagents, and controls for reliable interpretation of
      results. For the internal comparison study, three different foods (soft cheese,
      coalfish, and smoked ham) were analyzed, chosen from the 15 food groups
      recommended by the AOAC Research Institute for detection of L. monocytogenes.
      From each food, 20 samples were inoculated with a low level (1-10 CFU/25 g) and
      20 samples with a high level (10-50 CFU/25 g) of L. monocytogenes. Additionally,
      five nonspiked samples were prepared from each food. Depending on the matrix, the
      food samples were examined with the test kits and compared with the cultural
      methods according to the U.S. Food and Drug Administration's Bacteriological
      Analytical Manual or the U.S. Department of Agriculture/Food Safety and
      Inspection Service Microbiology Laboratory Guidebook.

PMID- 22468347
TI  - Detection of Salmonella in meat: comparative and interlaboratory validation of a
      noncomplex and cost-effective pre-PCR protocol.
AB  - Cost-effective and rapid monitoring of Salmonella in the meat production chain
      can contribute to food safety. The objective of this study was to validate an
      easy-to-use pre-PCR sample preparation method based on a simple boiling protocol
      for screening of Salmonella in meat and carcass swab samples using a real-time
      PCR method. The protocol included incubation in buffered peptone water,
      centrifugation of an aliquot, and a boiling procedure. The validation study
      included comparative and interlaboratory trials recommended by the Nordic
      Organization for Validation of Alternative Microbiological Methods (NordVal). The
      comparative trial was performed against a reference method (NMKL 187, 2007) and a
      PCR method previously approved by NordVal with a semiautomated magnetic bead
      based DNA extraction step using 122 artificially contaminated samples. The LOD
      was found to be 3.0, 3.2, and 3.4 CFU/sample for the boiling, magnetic bead
      based, and NMKL 187 methods, respectively. When comparing the boiling method with
      the magnetic beads, the relative accuracy (AC), relative sensitivity (SE), and
      relative specificity (SP) were 98, 102, and 98%, respectively (Cohen's kappa
      index 0.95). When comparing results obtained by the boiling to the culture-based
      method, the AC, SE, and SP were found to be 98, 102, and 98%, respectively (kappa
      index 0.93). In the interlaboratory trial including valid results from 11
      laboratories, apart from two false-positive samples by the boiling method
      combined with PCR, no deviating results were obtained (SP, SE, and AC were 100,
      95, and 97%, respectively). This test is under implementation by the Danish meat
      industry, and can be useful for screening of large number of samples in the meat
      production, especially for fast release of minced meat with a short shelf life.

PMID- 22468348
TI  - Comparative evaluation of the association among enumeration methods and
      production of enterotoxins in food-derived Staphylococcus aureus.
AB  - Staphylococcal food poisoning is one of the most common foodborne diseases
      worldwide; it results from the ingestion of staphylococcal enterotoxins (SEs) in
      food, mainly Staphylococcus aureus. This study investigated the statistical
      relationships among morphological enumerations of food-derived S. aureus and
      production of SEs using different methodologies. Food samples naturally
      contaminated with coagulase-positive S. aureus were submitted for enumeration on
      Baird-Parker (BP) agar, Rabbit Plasma Fibrinogen agar (RPFA), and Petrifilm Staph
      Express count system (STX), and the morphologically typical colonies were
      isolated for VIDAS and real-time (RT) PCR tests. RPFA and STX displayed better
      performance for the enumeration of SE-positive S. aureus when compared with BP,
      including higher frequencies of SE-positive isolates and better correlation
      indices between typical and SE-positive counts. Among all the evaluated culture
      media, no significant difference (P > 0.05) was shown on the frequencies of
      typical colonies that carried 11 individual se genes. In addition, results for SE
      identification between VIDAS and RT-PCR assay were unparalleled. These data will
      be valuable for the selection of methods for inspection of food-derived S.
      aureus.

PMID- 22468349
TI  - Extension of the validation of AOAC Official Method 2005.06 for dc-GTX2,3:
      interlaboratory study.
AB  - AOAC Official Method(SM) 2005.06 for the determination of saxitoxin (STX)-group
      toxins in shellfish by LC with fluorescence detection with precolumn oxidation
      was previously validated and adopted First Action following a collaborative
      study. However, the method was not validated for all key STX-group toxins, and
      procedures to quantify some of them were not provided. With more STX-group toxin
      standards commercially available and modifications to procedures, it was possible
      to overcome some of these difficulties. The European Union Reference Laboratory
      for Marine Biotoxins conducted an interlaboratory exercise to extend AOAC
      Official Method 2005.06 validation for dc-GTX2,3 and to compile precision data
      for several STX-group toxins. This paper reports the study design and the results
      obtained. The performance characteristics for dc-GTX2,3 (intralaboratory and
      interlaboratory precision, recovery, and theoretical quantification limit) were
      evaluated. The mean recoveries obtained for dc-GTX2,3 were, in general, low (53.1
      58.6%). The RSD for reproducibility (RSD(r)%) for dc-GTX2,3 in all samples ranged
      from 28.2 to 45.7%, and HorRat values ranged from 1.5 to 2.8. The article also
      describes a hydrolysis protocol to convert GTX6 to NEO, which has been proven to
      be useful for the quantification of GTX6 while the GTX6 standard is not
      available. The performance of the participant laboratories in the application of
      this method was compared with that obtained from the original collaborative study
      of the method. Intralaboratory and interlaboratory precision data for several STX
      group toxins, including dc-NEO and GTX6, are reported here. This study can be
      useful for those laboratories determining STX-group toxins to fully implement
      AOAC Official Method 2005.06 for official paralytic shellfish poisoning control.
      However the overall quantitative performance obtained with the method was poor
      for certain toxins.

PMID- 22468350
TI  - Immunoaffinity column cleanup with liquid chromatography using postcolumn
      bromination for the determination of aflatoxins in black and white sesame seed:
      single-laboratory validation.
AB  - A single-laboratory validation was conducted to establish the effectiveness of an
      immunoaffinity column cleanup procedure followed by LC with fluorescence
      detection for the determination of aflatoxins B1, B2, G1, and G2 in sesame seeds.
      The sample is homogenized with 50% water (w/w) to form a slurry, then the test
      portion is extracted with methanol-water (60 + 40, v/v) using a high-speed
      blender. The sample extract is filtered, diluted with 15% Tween 20 in phosphate
      buffered saline solution, and applied to an immunoaffinity column. Aflatoxins are
      removed with neat methanol, then directly determined by RP-LC with fluorescence
      detection using postcolumn bromination (Kobra cell). Test portions of blank white
      sesame seed slurry were spiked with a mixture of aflatoxins to give total levels
      of 4 and 10 microg/kg. Recoveries for individual and total aflatoxins ranged from
      92.7 to 110.3% for spiked samples. Based on results for spiked sesame paste
      (triplicates at two levels), the RSD for repeatability (RSD(r)) averaged 1.1% for
      total aflatoxins and 1.4% for aflatoxin B1. The method was demonstrated to be
      applicable to naturally contaminated samples of black and white sesame seeds
      obtained from local markets in China.

PMID- 22468351
TI  - Refinement of AOAC Official Method 2005.06 liquid chromatography-fluorescence
      detection method to improve performance characteristics for the determination of
      paralytic shellfish toxins in king and queen scallops.
AB  - AOAC Official Method 2005.06 LC-fluorescence detection (FLD) method is an
      official alternative to the mouse bioassay for the determination of paralytic
      shellfish poisoning (PSP) toxins in bivalve shellfish. To validate the method for
      species of relevance to the UK official control monitoring program, the method
      performance characteristics were tested for whole king and queen scallops.
      Validation showed that, while the performance was generally acceptable for the
      quantitation of non-N-hydroxylated toxins, poor toxin recovery and sensitivity
      was evident for the analysis of N-hydroxylated toxins following periodate
      oxidation. These effects occurred in a range of scallop samples with variable
      temporal and spatial sources. The effects were also noted in other laboratories
      following a small interlaboratory study. As a result, the method was refined to
      improve the recovery and sensitivity of analysis following the periodate
      oxidation step in the PSP method for scallops. Performance improved through
      alterations to the preparation of the periodate oxidant, use of higher volumes
      for C18 cleanup, and injection volumes in combination with the use of a king
      scallop matrix modifier for oxidation of N-hydroxylated toxin calibration
      standards. A single-laboratory validation of the refined method showed that the
      selectivity, linearity, sensitivity, recovery, and precision were acceptable and
      similar to values reported previously for AOAC Official Method 2005.06 in other
      bivalve species. Results showed the method to be rugged for all parameters
      investigated, including small changes to the composition of the new periodate
      reagent utilized in the refined method. The refined scallops LC method was
      subsequently compared with the European reference method. PSP-positive scallops
      showed an excellent agreement between the methods for queen and Atlantic
      scallops, with a small level of positive bias in the LC results for whole king
      scallops. These differences were related solely to the use of the highest
      toxicity equivalence factors for toxin epimeric pairs, with gonyautoxin (GTX)1,4
      and GTX2,3 in particular present at high concentrations in the king scallops.
      Overall, the refined LC-FLD method improved the performance characteristics of
      AOAC Official Method 2005.06 for the determination of PSP toxins in whole king
      and queen scallops, and showed a good overall agreement between the official
      methodologies. It is, therefore, recommended as a more appropriate option for the
      routine monitoring of PSP toxins in these species.

PMID- 22468352
TI  - Pantothenic acid (vitamin B5) in fortified foods: comparison of a novel ultra
      performance liquid chromatography-tandem mass spectrometry method and a
      microbiological assay (AOAC Official Method 992.07).
AB  - A novel method was developed and single-laboratory validated for the
      determination of free pantothenic acid (vitamin B5) in a wide range of infant and
      adult fortified food products. The method combines simple sample preparation and
      chromatographic analysis using ultra-performance LC coupled to tandem MS with
      positive electrospray ionization. Pantothenic acid was quantified using [13C6,
      15N2]-pantothenic acid as an internal standard. Calibration curves were linear
      between 0.08 and 1.2 microg/mL (r2 = 0.9998), and average recovery varied between
      95 and 106%. The method exhibited overall RSD(r) of 1.1% and RSD intermediate
      reproducibility from 2.5 to 6.0% in infant formulas and cereals. Comparison of
      results between total and free pantothenic acid showed that the analysis of free
      pantothenic acid gave a good estimation of total pantothenic acid in the range of
      products analyzed. The method provides reliable free pantothenic acid results in
      a wide range of fortified foods (infant and adult nutritionals, cereal products
      and beverages), and shows good correlation with the microbiological method AOAC
      Official Method 992.07. It is a more selective, faster, and robust alternative to
      microbiological determination.

PMID- 22468353
TI  - Detection of hazelnut in foods using ELISA: challenges related to the
      detectability in processed foodstuffs.
AB  - Hazelnuts are widely used nowadays, and can pose a serious threat to allergic
      consumers due to cross-contamination that may occur during processing. This might
      lead to the presence of hidden hazelnut in foods. Therefore, reliable tests are
      needed to detect hazelnut, especially in processed foods. A hazelnut-specific
      indirect competitive ELISA based on polyclonal chicken antibodies was developed.
      The polyclonal antibodies were raised against modified hazelnut proteins in order
      to improve the detectability of hazelnut proteins in processed foods. The assay
      showed a detection limit of 1.36 microg hazelnut protein/mL of 5 mM urea in
      phosphate-buffered saline buffer (pH 7.4). Limited cross-reactivity with walnut
      and pecan nut was observed; no cross-reactivity was observed with other food
      ingredients. Blank cookies spiked before analysis showed recoveries of 73-107%.
      However, cookies spiked before baking showed that the detectability was severely
      decreased. Addition of lactose to the cookies, which led to more severe
      modification through the Maillard reaction, led to an increase in the
      detectability. These results indicate that using antibodies developed toward
      allergens modified through food processing-simulating reactions is a better
      approach for detection.

PMID- 22468354
TI  - Determination of total choline by liquid chromatography-electrospray ionization
      tandem mass spectrometry in infant formulas.
AB  - Choline is a water-soluble nutrient important for infants' brain and neural
      development. In infant formulas, choline is one of the important fortified
      nutrients. A single-laboratory validation study conducted an LC-electrospray
      ionization-MS/MS to determine total choline in infant formulas. Sample
      preparation was adopted from AOAC Official Method 999.14, and instrumental
      running conditions were optimized. The LOQ was 0.2 microg/100 g, which is
      significant for measuring total choline in infant formulas. Average recoveries
      for milk-, rice-, soybean-, and hydrolyzed protein-based samples ranged from
      86.45 +/- 6.04% to 108.98 +/- 3.68%, with RSD less than 7%. The repeatability RSD
      (RSD(r)) range was 0.24-3.59% in within-day evaluation and 1.16-3.24% in day-to
      day evaluation. Matrix effect was also investigated, and can be effectively
      eliminated by using an internal standard. Therefore, this method has high
      credibility, and could be used as a routine method of quality control, or for
      clinical studies and other research areas.

PMID- 22468355
TI  - Composition of pomegranate juice.
AB  - A database of 793 commercial pomegranate juices was analyzed to produce a profile
      for authentication of pure pomegranate juice. The database consisted of data from
      a mix of authentic and adulterated samples. Statistical tools were used to reduce
      the database to a stable sample set of 477 presumably authentic samples. The
      profile obtained (mean, SD at 16 Brix) are as follows: fructose (g/100 g) 6.83,
      0.50; glucose (g/100 g) 6.66, 0.44; sucrose (g/100 g) 0.00, 0.00; sorbitol (g/100
      g) 0.00, 0.01; acidity (g/100 g as citric acid) 1.25, 0.32; citric acid (g/100 g)
      1.19, 0.30; malic acid (g/100 g) 0.065, 0.034; tartaric acid (g/100 g) 0.00,
      0.00; isocitric acid (mg/kg) 63, 21; potassium (mg/kg) 2320, 400; proline (mg/kg)
      7, 5; formol value [milliequivalents/100 g] 1.00, 0.24; 13C/12C ratio [o/oo Pee
      Dee belemnite]-26.4, 0.8. The profile samples had a consistent anthocyanin
      pattern consisting of four major peaks corresponding to delphinidin-3,5
      diglucoside, delphinidin-3-glucoside, cyanidin-3,5-diglucoside, and cyanidin-3
      glucoside. Minor peaks corresponding to pelargonidin-3,5-diglucoside and
      pelargonidin-3-glucoside were also generally present. No maltose, D-malic acid,
      or tartaric acid were detected in any of the samples. The profile obtained
      corresponds closely with previously published data.

PMID- 22468356
TI  - Determination of total iodine in infant formula and nutritional products by
      inductively coupled plasma/mass spectrometry: single-laboratory validation.
AB  - A single-laboratory validation by inductively coupled plasma-mass spectrometry
      was developed for the determination total iodine (m/z 127) in infant formula and
      adult nutritional products. All samples were digested in nitric acid using a
      closed vessel microwave oven system; Te (m/z 130) was used as an internal
      standard. To prevent loss of iodine, ammonium hydroxide solution was added to the
      samples immediately after digestion. The method quantitation limit for total
      iodine was 0.3 ng/mL, but a practical LOQ was used at 1.0 ng/mL, a concentration
      at which there was a negligible bias due to nonlinearity. The total iodine
      concentrations (112-1900 ng/g) in 14 out of 15 nutritional products were within
      specification limits. Within-day and day-to-day (6 independent days) precision
      values were < 10% RSD. The observed precision for the overall mean (18
      independent days) of a control sample was approximately 4% RSD. In two National
      Institute of Standards and Technology standard reference materials, total iodine
      results were within certified limits. Sample spike recoveries for all 15
      nutritional products were 92-105%. The data show that a conventional microwave
      oven digestion procedure can be used to prepare samples for iodine determination.
      Therefore, this technique is very compatible with other methods being proposed as
      modern official methods for the analysis of minerals in nutritional products.

PMID- 22468357
TI  - Determination of calcium, copper, iron, magnesium, manganese, potassium,
      phosphorus, sodium, and zinc in fortified food products by microwave digestion
      and inductively coupled plasma-optical emission spectrometry: single-laboratory
      validation and ring trial.
AB  - A single-laboratory validation (SLV) and a ring trial (RT) were undertaken to
      determine nine nutritional elements in food products by inductively coupled
      plasma-optical emission spectrometry in order to modernize AOAC Official Method
      984.27. The improvements involved extension of the scope to all food matrixes
      (including infant formula), optimized microwave digestion, selected analytical
      lines, internal standardization, and ion buffering. Simultaneous determination of
      nine elements (calcium, copper, iron, potassium, magnesium, manganese, sodium,
      phosphorus, and zinc) was made in food products. Sample digestion was performed
      through wet digestion of food samples by microwave technology with either closed-
      or open-vessel systems. Validation was performed to characterize the method for
      selectivity, sensitivity, linearity, accuracy, precision, recovery, ruggedness,
      and uncertainty. The robustness and efficiency of this method was proven through
      a successful RT using experienced independent food industry laboratories.
      Performance characteristics are reported for 13 certified and in-house reference
      materials, populating the AOAC triangle food sectors, which fulfilled AOAC
      criteria and recommendations for accuracy (trueness, recovery, and z-scores) and
      precision (repeatability and reproducibility RSD, and HorRat values) regarding
      SLVs and RTs. This multielemental method is cost-efficient, time-saving,
      accurate, and fit-for-purpose according to ISO 17025 Norm and AOAC acceptability
      criteria, and is proposed as an extended updated version of AOAC Official Method
      984.27 for fortified food products, including infant formula.

PMID- 22468358
TI  - Multiplex, construct-specific, and real-time PCR-based analytical methods for Bt
      rice with cry1Ac gene.
AB  - Qualitative and quantitative analytical methods based on PCR for Bacillus
      thuringiensis (Bt) rice hybrid, namely, MRP 5401 Bt expressing a modified version
      of the Bt cry1Ac gene, are reported here. Multiplex PCR assays were developed to
      target the cry1Ac transgene, Cauliflower mosaic virus (CaMV) 35S promoter,
      Agrobacterium tumefaciens nopaline synthase (nos) terminator, the neomycin
      phosphotransferase II (nptLL) marker gene, and an endogenous a-tubulin (TubA)
      gene in Bt rice. The 3.178 kb region of inserted gene construct comprising the
      region of the CaMV 35S promoter and cry1Ac gene was amplified, and the construct
      integrity was confirmed by the nested PCR. The LOD for cry1Ac gene-specific
      simplex PCR was 0.01%, as established using Bt rice DNA dilutions with 100, 10,
      1.0, 0.1, 0.05, 0.01, and 0.001% genetically modified trait. A real-time PCR
      assay was also developed to quantify the cry1Ac gene. The method performance of
      the reported real-time PCR assay was in line with the acceptance criteria of
      Codex Alimentarius Commission ALINORM 10/33/23, with LOD and LOQ values of 0.05%.
      The reliable PCR assays prior to commercial release of Bt rice would facilitate
      efficient regulatory compliance for identification of genetic trait, labeling
      requirements, and effective risk assessment and management. They could also
      address consumers' concerns and legal disputes that may arise.

PMID- 22468359
TI  - Determination of total iodine in foods and dietary supplements using inductively
      coupled plasma-mass spectrometry.
AB  - A method was developed and validated for the determination of total iodine in a
      wide variety of food products and dietary supplements. The method involves a
      unique sample digestion with a KOH solution in an oven or by using an open-vessel
      microwave system. After digestion, a stabilizer is added and the solution is
      taken to volume, then filtered and analyzed either directly or after dilution.
      The amount of iodine is determined with inductively coupled plasma-mass
      spectrometry (ICP-MS). The method was validated by experiments to determine its
      precision, accuracy, linearity, specificity, ruggedness, and robustness. The LOQ
      of this method is 25-50 microg/kg. The method demonstrated an average RSD of
      2.27% during analysis of milk powder and 4.30% during analysis of a dietary
      supplement tablet reference material. The accuracy of the method as determined
      with these same reference materials was 100 and 94.2%, respectively. The method
      has been used successfully on commodity foods, processed foods, dairy products,
      pet food, infant formula, animal feed, mineral premixes, and a variety of dietary
      supplements.

PMID- 22468360
TI  - Developing a modified preservative efficacy testing approach as a predictive tool
      for the evaluation of preservative systems in liquid home care products under
      variable test conditions.
AB  - How can a formulator have confidence that a preservative system will perform as
      expected under adverse conditions? Extreme conditions that can lead to the
      development of "off odors" in the product can be a serious challenge for
      companies providing home care products in the global market. Formulation and
      stability testing occur under controlled parameters that simulate limited
      environmental conditions and microbial challenges are typically performed with a
      standard inoculum level. While this is an acceptable and dependable process, it
      does not necessarily assess how well a preservative system can perform under
      extreme environmental conditions or against unusually high levels of bacterial
      challenges. This is especially true when formulations are diluted and stored by
      the end-user. By modifying microbial challenge testing of a liquid dishwashing
      product to include unexpected dilution schemes, increased microbial assaults, and
      elevated temperatures, a pattern of preservative efficacy was established. The
      resulting approach proved to be a useful tool when developing use directions,
      recommended dilution levels, the overall surfactant system, preservative type,
      and storage restrictions.

PMID- 22468361
TI  - Validation of a new enzyme-linked immunosorbent assay to detect the triggering
      proteins and peptides for celiac disease: interlaboratory study.
AB  - The performance of Gluten-Tec (EuroProxima, Arnhem, The Netherlands) was tested
      through an interlaboratory study in accordance with AOAC guidelines. Gluten-Tec
      is a competitive ELISA that detects an immunostimulatory epitope of a-gliadin in
      dietary food for celiacs. Fifteen laboratories, representing 14 different
      countries, announced their interest in taking part in this study. Of the 12
      laboratories that sent the results within the established timeframe, two
      submitted inappropriate standard curves and were excluded from the statistical
      analysis. Four different food matrixes (rice-based baby food, maize bread,
      chocolate cake mix, and beer) were selected for preparing the test samples. Two
      gliadin extraction procedures were used: the conventional 60% ethanol, and a new
      method based on the reducing reagent dithiothreitol. The 38 samples (19 blind
      duplicates) tested in this study were prepared by diluting the different extracts
      in order to cover a wide range of gliadin levels. Both sample extraction and
      dilution were performed by EuroProxima; the present interlaboratory study was
      focused only on testing the ELISA part of the Gluten-Tec kit protocol.
      Repeatability values (within-laboratory variance), expressed as RSD(r) ranged
      from 6.2 to 25.7%, while reproducibility values (interlaboratory variance),
      expressed as RSD(R), ranged from 10.6 to 45.9%. Both statistical parameters were
      in the acceptable range of ELISAs under these conditions, and the method will be
      presented to the Codex Alimentarius as a preferred method for gluten analysis.

PMID- 22468362
TI  - New role of antibody in bacterial isolation.
AB  - To eliminate the interference caused by Pseudomonas aeruginosa in the isolation
      of Salmonella, a rabbit polyclonal antibody against P. aeruginosa was prepared by
      inoculating four New Zealand rabbits with the pathogen. The antiserum was
      purified using saturated ammonium sulfate and added into Rappaport-Vassiliadis
      medium with soya (RVS) broth and Muller-Kauffmann tetrathionate novobiocin broth
      (MKTTn broth) to evaluate whether it could inhibit the growth of P. aeruginosa.
      Observations by scanning electron microscopy demonstrated that P. aeruginosa was
      attacked and destroyed by the antibody when incubated for 10 min at 37 degrees C.
      The activity of the antibody was also effective against 11 other strains of P.
      aeruginosa. Twenty-six strains of Salmonella were mixed with P. aeruginosa in RVS
      and MKTTn broth at 37 degrees C for 12 h, respectively, and the cultures were
      plated on Salmonella chromogenic medium (SCM; Oxoid, Basingstoke, UK). Only
      Salmonella grew on SCM; five colonies were randomly selected for identification
      by VITEK 2 (bioMerieux, Lyon, France). Additionally, when mixed with two strains
      of Enterobacter cloacae (ATCC 700323 and YG001), the prepared antibody did not
      affect the growth of E. cloacae. The results demonstrated that the microbicidal
      activity of the antibody did not affect the tested Salmonella sp. or E. cloacae
      strains. Therefore, the antibody generated could be used to increase the accuracy
      of Salmonella isolation.

PMID- 22468363
TI  - Development of a headspace-solid phase microextraction-gas chromatography method
      to determine organohalogen contamination in drinking water.
AB  - The formation of organohalogen compounds in waters treated by chlorination has
      drawn increasing scientific attention due to the potentially hazardous health
      effects of this class of substances. Today, chlorination is the most widely used
      technology for civil water disinfection. In this study, headspace-solid phase
      microextraction coupled with GC-electron capture detector was used to determine
      organohalogen compounds in drinking water sampled from aqueducts and artesian
      wells in Italy. Experimental parameters, such as sample volume, stirring, salting
      out, extraction temperature, and extraction time, were evaluated and optimized.
      The LODs ranged from 1 to 10 ng/L and LOQs from 5 to 50 ng/L. A linear response
      was confirmed by correlation coefficients ranging from 0.9443 to 0.9999.
      Quantifiable organohalogen residues were found in 11 water samples, with
      concentration up to 11.3 +/- 0.5 microg/L for the sum of all trihalomethanes and
      0.66 +/- 0.03 microg/L for the sum of trichloroethylene and tetrachloroethylene.
      These concentrations are lower than the current regulatory limits in Italy.

PMID- 22468364
TI  - Spectrophotometric determination of mercury in water samples after
      preconcentration using dispersive liquid-liquid microextraction.
AB  - A simple method for the determination of mercury in water samples after
      preconcentration using dispersive liquid-liquid microextraction is described. The
      procedure is based on the extraction of mercury in the form of a complex and its
      subsequent determination by spectrophotometry. The complex is formed between
      Hg(II) and 2-(2-benzothiazolylazo)-p-cresol. The detection at 650 nm is performed
      directly in the metal-rich phase, which is spread on a triacetylcellulose
      membrane. The method eliminates the need to use a cuvet or large quantities of
      samples and reagents. The parameters that influence the preconcentration were
      studied, and the analytical characteristics were determined. The enrichment
      factor and the consumptive index for this method were 64 and 0.16 mL,
      respectively. The LOD (3.3 microg/L) and LOQ (11.1 microg/L) were also
      determined. The accuracy of the method was tested by the determination of mercury
      in certified reference materials BCR 397 (Human Hair) and SRM 2781 (Domestic
      Sludge). The method was applied to the determination of mercury in samples of
      drinking water, sea water, and river water.

PMID- 22468365
TI  - Evaluation of microwave-assisted extraction for the analysis of organophosphorus
      and pyrethroid pesticides in green onions.
AB  - The aim of this study was to evaluate the efficiency of microwave-assisted
      extraction (MAE) for the analysis of organophosphorus (OP) and pyrethroid (PYR)
      pesticides in green onions by GC/MS. We optimized MAE extraction solvent,
      temperature, and time by using a certified reference material. As a result, the
      concentrations of two OP and two PYR target pesticides obtained by MAE with
      acetonitrile at 110 degrees C for 10 min were in good agreement with certified
      concentrations and comparable to the results by homogenization used as reference
      extraction technique. When the recovery test, performed by spiking the target
      pesticides into blank samples (5.0 g), was carried out with our optimized MAE
      conditions, mean recoveries of 16 OP and 10 PYR pesticides were 72-108% for a 1.0
      pg spiking level and 70-119% for a 0.2 microg level. These results were
      acceptable according to the validation guideline for testing method of
      agricultural chemicals in food by Ministry of Health, Labour, and Welfare in
      Japan. The results suggested that MAE can be used for the analysis of OP and PYR
      pesticides in green onions.

PMID- 22468366
TI  - Determination of natural pesticides in fresh fruits using liquid
      chromatography/mass spectrometry.
AB  - An analytical procedure was developed for the determination of some natural
      pesticides (piperonyl butoxide, nicotine, rotenone, spinosad, and abamectin B1a)
      in fruit matrixes. The quick, easy, cheap, effective, rugged, and safe (QuEChERS)
      method was used for extraction. Analysis of the extract was performed by LC
      electrospray ionization (ESI)-MS/MS. The ions prominent in the ESI spectra were
      [M+Na]+ for abamectin B1a, [M+NH4]+ for piperonyl butoxide, and [M+H]+ for the
      rest of the compounds. A Zorbax SB-C18 column was used with a programmed gradient
      mobile phase consisting of (A) water containing 0.1% formic acid and 5 mM
      ammonium formate, and (B) acetonitrile containing 2 mM sodium acetate. The method
      was linear within the investigated concentration range, displaying a calibration
      curve correlation factor of 0.99. The CVs obtained were below 20%, and recoveries
      were in the 70-110% range.

PMID- 22468367
TI  - Variances and uncertainties of the sample laboratory-to-laboratory variance
      (S(L)2) and standard deviation (S(L)) associated with an interlaboratory study.
AB  - The validation process for an analytical method usually employs an
      interlaboratory study conducted as a balanced completely randomized model
      involving a specified number of randomly chosen laboratories, each analyzing a
      specified number of randomly allocated replicates. For such studies, formulas to
      obtain approximate unbiased estimates of the variance and uncertainty of the
      sample laboratory-to-laboratory (lab-to-lab) STD (S(L)) have been developed
      primarily to account for the uncertainty of S(L) when there is a need to develop
      an uncertainty budget that includes the uncertainty of S(L). For the sake of
      completeness on this topic, formulas to estimate the variance and uncertainty of
      the sample lab-to-lab variance (S(L)2) were also developed. In some cases, it was
      necessary to derive the formulas based on an approximate distribution for S(L)2.

PMID- 22468368
TI  - Validation of the Delvotest SP NT DA. Performance Tested Method 011101.
AB  - Delvotest SP NT DA is designed to test milk for the presence of antibacterial
      substances, such as antibiotics. The test is made of an agar gel containing
      bacterial spores and a color indicator. The milk sample is added onto the agar
      gel, and the test is incubated at 64 degrees C. The principle of the test is
      based on the diffusion of possible inhibitory substances that may be present in
      the milk sample into agar. This reduces growth and acid production by the test
      organism, and delays or prevents the agar from changing color from purple to
      yellow. The Delvotest Accelerator is an automated system in which the plates
      containing the milk to be analyzed are placed for incubation. The Accelerator
      automatically detects the end of the incubation and reads the results. A sample
      containing antibiotic will be noted as "positive." A sample without antibiotics
      or with antibiotics at concentrations below detection level will be noted as
      "negative." The present report includes all technical details about the Delvotest
      SP NT DA, and the results of the validation study. The validation study
      demonstrates that the Delvotest SP NT DA conforms to the product performance
      claims and confirms the robustness of the test. The Delvotest SP NT DA is,
      therefore, granted Performance Tested Method certification.

PMID- 22468369
TI  - Liquid chromatographic determination of quinolones in water and human urine
      samples after microextraction by packed sorbent.
AB  - A method for the simultaneous determination of quinolones in water and urine
      samples by microextraction in a sorbent-packed syringe (MEPS) with LC is
      described. MEPS is a new miniaturized SPE technique that can be used with
      chromatographic instruments without any modifications. In MEPS, approximately 1
      mg of the solid packing material is inserted into a syringe (100-250 microL) as a
      plug. Sample preparation takes place on the packed bed. The new method is
      promising, easy to use, economical, and rapid. The determination of quinolones in
      groundwater and urine was performed using MEPS as a sample preparation method
      with LC-UV determination. Four quinolone antibiotics--enrofloxacin, enoxacin,
      danofloxacin, and nalidixic acid--in groundwater and urine samples were used as
      analytes. The extraction recovery was found to be between 64.9 and 98.9%. The
      results showed high correlation coefficients (R2 > 0.992) for all of the analytes
      within the calibration range. The LOQ was between 0.091 and 0.315 ng/mL.

PMID- 22468370
TI  - AOAC INTERNATIONAL guidelines for validation of botanical identification methods.

PMID- 22468371
TI  - Probability of identification: a statistical model for the validation of
      qualitative botanical identification methods.
AB  - A qualitative botanical identification method (BIM) is an analytical procedure
      that returns a binary result (1 = Identified, 0 = Not Identified). A BIM may be
      used by a buyer, manufacturer, or regulator to determine whether a botanical
      material being tested is the same as the target (desired) material, or whether it
      contains excessive nontarget (undesirable) material. The report describes the
      development and validation of studies for a BIM based on the proportion of
      replicates identified, or probability of identification (POI), as the basic
      observed statistic. The statistical procedures proposed for data analysis follow
      closely those of the probability of detection, and harmonize the statistical
      concepts and parameters between quantitative and qualitative method validation.
      Use of POI statistics also harmonizes statistical concepts for botanical,
      microbiological, toxin, and other analyte identification methods that produce
      binary results. The POI statistical model provides a tool for graphical
      representation of response curves for qualitative methods, reporting of
      descriptive statistics, and application of performance requirements. Single
      collaborator and multicollaborative study examples are given.

PMID- 22468372
TI  - [Four cases of risky "doctor's delay". Children and adolescents with newly onset
      diabetes are hospital emergencies].

PMID- 22468373
TI  - [An attempt to introduce testosterone to healthy men. A shameful campaign].

PMID- 22468374
TI  - [Authorities in USA don't recommend screening for prostate cancer].

PMID- 22468375
TI  - [Chagas' disease in Sweden--great need of guidelines for testing. Probably
      hundreds of seropositive cases, only a few known].

PMID- 22468376
TI  - [Negative pressure wound therapy. Knowledge of effect mechanisms and
      complications yield new possibilities].

PMID- 22468377
TI  - [Antibiotic resistance in children with urinary diversion is common].

PMID- 22468378
TI  - [Does the doctor know what a child's bottom looks like? Late detection of
      anorectal abnormalities in children].

PMID- 22468379
TI  - [GlaxoSmithKline requires additional consideration of the national procurement of
      cancer vaccine: Procurement of HPV vaccine is not consistent with good
      scientific, ethical and moral practice].

PMID- 22468380
TI  - ["...the knowledge of being able to live a life richer than most". About Clarence
      Blomquist--pioneer of medical ethics in Sweden].

PMID- 22468381
TI  - [Interns' competence development. Quality of the assessment must be improved].

PMID- 22468382
TI  - [Increasing societal costs of Parkinson disease and Alzheimer disease. Aging
      population and medical progress yield more and more expensive care].

PMID- 22468383
TI  - [Hyperhidrosis--the "silent" handicap].

PMID- 22468384
TI  - [Botulinum toxin helps against primary local hyperhidrosis. Good effect--few
      adverse effects according to a literature review].

PMID- 22468385
TI  - [Splenic injury in colonoscopy--potentially fatal complications].

PMID- 22468386
TI  - [Hippocrates in our time].

PMID- 22468387
TI  - [The discussion on target goals in lipid reduction is still going on. The Expert
      Committee--a block for current cardiovascular prevention].

PMID- 22468388
TI  - [Visions are good but the guidelines require evidence].

PMID- 22468389
TI  - [Neuropsychiatric diseases: the biggest challenge of this century for health care
      authorities].

PMID- 22468390
TI  - [Sweden should introduce mandatory folic acid fortification. Risk of cancer is
      not convincingly proved--neural tube defect prophylaxis is more important].

PMID- 22468391
TI  - [Alarming overweight and obesity figures in Sweden and in the world].

PMID- 22468392
TI  - [Bariatric surgery or the fairy tale about the ugly duckling].

PMID- 22468393
TI  - [Accelerating development of bariatric surgery in Sweden].

PMID- 22468394
TI  - [Long way towards a successful drug treatment of obesity].

PMID- 22468395
TI  - [Behavior modification--the only plausible therapy of obesity in children and
      adults].

PMID- 22468396
TI  - [The mandometer method helps obese persons to regulate their food intake].

PMID- 22468397
TI  - [More and more commercial programs offer weight reduction via Internet].

PMID- 22468398
TI  - [From chaos to order with programs against obesity].

PMID- 22468399
TI  - [Cross-stitch embroidery and premenstrual problems].

PMID- 22468400
TI  - [New principles from American Pediatric Society. Investigation of small children
      with pyelitis needs to be renewed].

PMID- 22468401
TI  - [Alarming use of anti-VEGF therapy in premature infants].

PMID- 22468402
TI  - [School meals--too little folate?].

PMID- 22468403
TI  - [The emperor didn't believe in medicine--just in physicians].

PMID- 22468404
TI  - [Health personnel the key to high vaccination coverage against influenza].

PMID- 22468405
TI  - [Troponin can be increased in healthy persons following moderate exercise].

PMID- 22468406
TI  - [Interior safety in trains neglected. A case study after the train crash in
      Kimstad].

PMID- 22468407
TI  - [Cardiovascular risk in inflammatory systemic disease should be assessed
      regularly. The Swedish Society of Rheumatology has formulated guidelines for
      primary prevention].

PMID- 22468408
TI  - [Cystic echinococcosis. An imported severe parasitic disease].

PMID- 22468409
TI  - [TRALI is an overlooked transfusion reaction. Can be life-threatening, increased
      knowledge among Swedish physicians is needed].

PMID- 22468410
TI  - [Possible connection between lymphocytic colitis and sertraline treatment].

PMID- 22468411
TI  - [Let the defence have access to forensic expertise, too].

PMID- 22468412
TI  - [Rheumatologic research with animal experiments is important for our patients].

PMID- 22468413
TI  - [Searching for a biological marker common for both ADHD and EDS].

PMID- 22468414
TI  - [The power of the word over the thought].

PMID- 22468415
TI  - Does expressed acceptance reflect genuine attitudes? A bogus pipeline study of
      the effects of mortality salience on acceptance of a person with AIDS.
AB  - The present study examined whether expressed acceptance of a person with AIDS
      reflects genuine acceptance or a desire to appear to be accepting. Theory and
      research on the effects of mortality salience on acceptance of stigmatized people
      provided the framework for investigating this question. After writing about death
      or another aversive topic, participants indicated their acceptance of a target
      with AIDS while connected to physiological equipment that they believed could
      detect lies (bogus pipeline) or was simply measuring physiological responses to
      participation in the study. As predicted, participants in the mortality
      salience/bogus pipeline condition indicated significantly less acceptance of the
      target with AIDS than participants in the other three conditions, suggesting that
      acceptance of a person with AIDS is at least partially a result of wanting to
      appear to be accepting, without necessarily genuinely accepting someone with
      AIDS.

PMID- 22468416
TI  - Growth motivation as a moderator of behavioral self-handicapping in women.
AB  - Behavioral self-handicapping is a strategy used to protect attributions about
      ability. People behaviorally self-handicap by creating an obstacle to their
      success so failure is attributed to the obstacle instead of to their ability.
      Although past research has observed behavioral self-handicapping exclusively in
      men, the current research revealed a moderator of behavioral self-handicapping in
      women: growth motivation, which reflects the desire to develop one's abilities
      and learn from failure. Participants (N = 100) completed a test purportedly
      predictive of successful careers and relationships, and some were given failure
      feedback about their performance. Participants could behaviorally self-handicap
      by choosing to complete another test in a performance-impairing environment.
      Although men self-handicapped more overall, women self-handicapped more after
      failure when they were low in growth motivation. These results highlight a novel
      moderator of behavioral self-handicapping in women.

PMID- 22468417
TI  - The homicidol effect: investigating murder as a fitness signal.
AB  - This article extends homicide adaptation theory by investigating signal effects
      of a murder. In two experiments (N = 299 and N = 161) participants reported their
      perceptions of a described person. The first study manipulated the information
      about the person (including or excluding a single sentence stating that the
      person has committed a murder) and stimulus person/observer sex match (same vs.
      opposite sex). Results suggest that murder functions as a signal of the described
      person's fitness that enhances observers' evaluations and inclination to interact
      with the person. Opposite-sex observers evaluate the murderer's intent more
      favorably than same-sex observers, but these evaluations of intent produce
      differential (positive vs. negative) effects between the two groups. The second
      study replicated the findings and ruled out potential confounds.

PMID- 22468418
TI  - Ingroup ambivalence and experienced discomfort: the moderating roles of affective
      versus cognitive attitudinal basis, group identification, as mediated by negative
      beliefs about the ingroup.
AB  - Prior research has found individuals' reactions to vary depending on whether such
      associations are activated by emotions (an affective basis) or by beliefs (a
      cognitive basis) about the object's properties. Accordingly, this conceptual
      distinction should be relevant also for the discomfortive responses to one's
      ambivalent attitudes regarding fellow group members (or the ingroup). Findings
      from two studies support the argument that ambivalence-associated discomfort a)
      is a general tendency when it regards affect-based ambivalence towards fellow
      group members, while b) only holds for the more identified group members when
      ambivalence concerns beliefs about the ingroup, and for this latter group members
      c) this tendency is driven by the strength of their negative beliefs about the
      ingroup or fellow group members.

PMID- 22468419
TI  - More than just a pretty face and a hot body: multiple cues in mate-choice.
AB  - Mate preferences have been well studied in social and evolutionary psychology. In
      two studies (N = 490), using two different measurement techniques, we examined
      mate preferences for the body and the face in the context of other traits.
      Results replicated prior research on mate preferences across the sex of the
      participant and mating duration but clarified the nature of preferences for
      physical attractiveness. Generally, physical attractiveness was a necessity in
      short-term mating and for men and traits like kindness were a necessity in long
      term mating and for women. Men wanted a short-term mate who had a good body,
      likely because that body advertises fertility whereas both sexes wanted a mate
      with a nice face for a long-term mate, which is likely because the face is a cue
      based on structural properties related to health. Sex and mating-duration
      differences on preferences for attractive faces and bodies were robust to
      differences in measurement technique.

PMID- 22468420
TI  - Control cognitions and causal attributions as predictors of fatigue severity in a
      community sample.
AB  - Control cognitions and causal attributions of fatigue were examined in relation
      to Weiner's Causal Attribution theory in a community sample. Participants were 97
      females and 43 males, aged 18-83 years. Weiner's dimensions of stability and
      uncontrollability and physical and psychosocial attributions of fatigue were
      related to fatigue severity. Escape-avoidance coping mediated between
      psychosocial causal attributions of fatigue to fatigue; whereas planful problem
      solving and exercise moderated between stability cognitions to fatigue and
      psychosocial attributions of fatigue to fatigue, respectively. This, the cause(s)
      of fatigue were perceived as stable, uncontrollable, and involving physical and
      psychosocial factors, participants reported worse fatigue. Taken together, the
      results suggest that fatigue treatments may be most effective when they are
      tailored or matched to the belief systems of the individuals with fatigue.

PMID- 22468421
TI  - Viewing death on television increases the appeal of advertised products.
AB  - References to death abound in many television programs accessible to most people.
      Terror Management Theory postulates that existential anxiety, which death
      reminders activate, may reinforce materialistic tendencies. The current article
      explores the effect of a death reminder in television shows on the desirability
      of advertised products. Consistent with Terror Management Theory's predictions,
      in two studies participants show greater desire for products, which were
      advertised immediately following clips from programs that featured a death scene,
      compared with programs that did not. Cognitive accessibility of death predicted
      the appeal difference while changes in affect or interest in the show did not.
      The findings are discussed in light on affective and existential theories which
      make opposite predictions. Implications and future directions are considered.

PMID- 22468422
TI  - What's in a face? The role of skin tone, facial physiognomy, and color
      presentation mode of facial primes in affective priming effects.
AB  - Participants (N = 106) performed an affective priming task with facial primes
      that varied in their skin tone and facial physiognomy, and, which were presented
      either in color or in gray-scale. Participants' racial evaluations were more
      positive for Eurocentric than for Afrocentric physiognomy faces. Light skin tone
      faces were evaluated more positively than dark skin tone faces, but the magnitude
      of this effect depended on the mode of color presentation. The results suggest
      that in affective priming tasks, faces might not be processed holistically, and
      instead, visual features of facial priming stimuli independently affect implicit
      evaluations.

PMID- 22468423
TI  - Matching the graphical display of data to avoidance versus approach motivation
      increases outcome expectancies.
AB  - This study is the first demonstration of the effect of motivational focus
      (approach vs. avoidance) on the interpretation of graphical view of personal
      data, specifically, weight loss progress. In two experiments, participants were
      randomly assigned to see the bogus weight loss data charted against either a goal
      or a baseline reference line. In the first experiment, we accessed participants'
      chronic motivational focus. In the second study, we primed motivation by exposing
      the participants to either a gain- or loss-focused health message. The results
      demonstrate that participants with either chronic or manipulated approach
      motivation predicted higher future weight loss in the goal reference line
      condition than in the baseline reference line condition. The opposite pattern was
      observed for participants with either chronic or manipulated avoidance
      motivation. The potential of matching graphical data display to personality
      characteristics to promote effective health management is discussed.

PMID- 22468424
TI  - Does regulating others' feelings influence people's own affective well-being?
AB  - Individuals in a variety of social contexts try to regulate other people's
      feelings, but how does this process affect the regulators themselves? This
      research aimed to establish a relationship between people's use of interpersonal
      affect regulation and their own affective well-being. In a field study, self- and
      other-reported data were collected from prisoners and staff members in a
      therapeutic prison using two surveys separated in time. In a laboratory study, a
      student sample reported their affect before and after attempting to influence the
      feelings of talent show contestants in a role-play task. The results of both
      studies indicated congruent associations between the use of affect-improving and
      affect-worsening interpersonal affect regulation and strategy agents' affective
      well-being. Our findings highlight that, when performing interpersonal affect
      regulation, people may not be immune from the effects of their own actions.

PMID- 22468425
TI  - Healthcare market review: A weak private sector is bad news for the NHS.

PMID- 22468426
TI  - Commissioning Board warns of 11 'key risks'.

PMID- 22468427
TI  - Private acute providers warned of slowing growth in NHS work.

PMID- 22468428
TI  - Innovate or regulate?

PMID- 22468429
TI  - We must wake up, not shake up.

PMID- 22468430
TI  - Roundtable: A lot to learn.

PMID- 22468431
TI  - Workforce: Getting off to a better start.

PMID- 22468432
TI  - Efficiency: Prescription for challenging times.

PMID- 22468434
TI  - Health bill: The NHS deserves a better, more open debate over health reform.

PMID- 22468433
TI  - FT leadership: How to find your way in the foundation landscape.

PMID- 22468435
TI  - Ricketts: 'seminal' report could shape NHS.

PMID- 22468436
TI  - Efficiency: Trust mulls 'wholesale' orporate outsourcing.

PMID- 22468437
TI  - Private providers rail against bankruptcy regime.

PMID- 22468438
TI  - Interview: Macmillan boss tackles the big C: commissioning. Interview by Nick
      Golding.

PMID- 22468439
TI  - Top of the to-do list.

PMID- 22468441
TI  - Clinical leaders: Up the leadership learning curve.

PMID- 22468440
TI  - Service transformation: People promote improvement.

PMID- 22468442
TI  - Innovation: Don't fight the future.

PMID- 22468443
TI  - Huge variation emerges in CCG funding.

PMID- 22468444
TI  - London trusts to run out of money by 2015.

PMID- 22468445
TI  - Sweat the assets.

PMID- 22468446
TI  - Old foes are fighting the same corner.

PMID- 22468447
TI  - On the CCG footprint.

PMID- 22468448
TI  - Disinvestment: Can you afford not to cut it?

PMID- 22468449
TI  - Integration: Everyone's a winner.

PMID- 22468450
TI  - Community services: Keep control of care, cost and capacity.

PMID- 22468451
TI  - Competition: Plan B for the Health Bill is dead, but Plan C lives on.

PMID- 22468452
TI  - Quality standards hit by spending squeeze.

PMID- 22468453
TI  - Service provision: Trust cools on cord blood collection plan.

PMID- 22468454
TI  - Debt cap planned for 'essential' providers.

PMID- 22468455
TI  - Competition is critical for reform.

PMID- 22468456
TI  - A hunger for quality.

PMID- 22468457
TI  - Innovation: When time really is money.

PMID- 22468458
TI  - Efficiency: Healthcare's coming home.

PMID- 22468459
TI  - Special issue on musculoskele modelling of the lower limb.

PMID- 22468460
TI  - On validation of multibody musculoskeletal models.
AB  - We review the opportunities to validate multibody musculoskeletal models in view
      of the current transition of musculoskeletal modelling from a research topic to a
      practical simulation tool in product design, healthcare and other important
      applications. This transition creates a new need for justification that the
      models are adequate representations of the systems they simulate. The need for a
      consistent terminology and established standards is identified and knowledge from
      fields with a more progressed state-of-the-art in verification and validation is
      introduced. A number of practical steps for improvement of the validation of
      multibody musculoskeletal models are pointed out and directions for future
      research in the field are proposed. It is hoped that a more structured approach
      to model validation can help to improve the credibility of musculoskeletal
      models.

PMID- 22468462
TI  - Comparison of different methods for estimating muscle forces in human movement.
AB  - The aim of this study was to compare muscle-force estimates derived for human
      locomotion using three different methods commonly reported in the literature:
      static optimisation (SO), computed muscle control (CMC) and neuromusculoskeletal
      tracking (NMT). In contrast with SO, CMC and NMT calculate muscle forces
      dynamically by including muscle activation dynamics. Furthermore, NMT utilises a
      time-dependent performance criterion, wherein a single optimisation problem is
      solved over the entire time interval of the task. Each of these methods was used
      in conjunction with musculoskeletal modelling and experimental gait data to
      determine lower-limb muscle forces for self-selected speeds of walking and
      running. Correlation analyses were performed for each muscle to quantify
      differences between the various muscle-force solutions. The patterns of muscle
      loading predicted by the three methods were similar for both walking and running.
      The correlation coefficient between any two sets of muscle-force solutions ranged
      from 0.46 to 0.99 (p < 0.001 for all muscles). These results suggest that the
      robustness and efficiency of static optimisation make it the most attractive
      method for estimating muscle forces in human locomotion.

PMID- 22468461
TI  - Knee joint forces: prediction, measurement, and significance.
AB  - Knee forces are highly significant in osteoarthritis and in the survival and
      function of knee arthroplasty. A large number of studies have attempted to
      estimate forces around the knee during various activities. Several approaches
      have been used to relate knee kinematics and external forces to internal joint
      contact forces, the most popular being inverse dynamics, forward dynamics, and
      static body analyses. Knee forces have also been measured in vivo after knee
      arthroplasty, which serves as valuable validation of computational predictions.
      This review summarizes the results of published studies that measured knee forces
      for various activities. The efficacy of various methods to alter knee force
      distribution, such as gait modification, orthotics, walking aids, and custom
      treadmills are analyzed. Current gaps in our knowledge are identified and
      directions for future research in this area are outlined.

PMID- 22468464
TI  - The development of lower limb musculoskeletal models with clinical relevance is
      dependent upon the fidelity of the mathematical description of the lower limb.
      Part I: Equations of motion.
AB  - Contemporary musculoskeletal modelling research is based upon the assumption that
      such models will evolve into clinical tools that can be used to guide therapeutic
      interventions. However, there are a number of questions that must be addressed
      before this becomes a reality. At its heart, musculoskeletal modelling is a
      process of formulating and then solving the equations of motion that describe the
      movement of body segments. Both of these steps are challenging. This article
      argues that traditional approaches to musculoskeletal modelling have been heavily
      influenced by the need to simplify this process (and in particular the solution
      process), and that this has to some degree resulted in approaches that are
      contrary to the principles of classical mechanics. It is suggested that future
      work is required to understand how these simplifications affect the outputs of
      musculoskeletal modelling studies. Equally, to increase their clinical relevance,
      the models of the future should adhere more closely to the classical mechanics on
      which they are based.

PMID- 22468463
TI  - Hybrid models of the neuromusculoskeletal system improve subject-specificity.
AB  - Muscle-actuated simulations of pathological gait have the capacity to identify
      muscle impairments and compensatory strategies, but the lack of subject-specific
      solutions prevents the prescription of personalized therapies. Conversely,
      electromyographic-driven models are limited to muscles for which data are
      available but can capture the true neural drive initiated by an individual
      subject. In order to improve subject-specificity and enforce physiological
      constraints on muscle activity, we propose a hybrid strategy for the optimization
      of subject-specific muscle patterns that involves forward dynamic simulation of
      whole body movement coupled with electromyographic-driven models of muscle
      subsets. In this paper we apply the hybrid approach to an example of post-stroke
      gait and demonstrate its unique ability to account for the unusual muscle
      activation patterns and muscle properties in patients with neuromuscular
      impairments.

PMID- 22468465
TI  - The development of lower limb musculoskeletal models with clinical relevance is
      dependent upon the fidelity of the mathematical description of the lower limb.
      Part 2: Patient-specific geometry.
AB  - Musculoskeletal models have the potential to evolve into sensitive clinical tools
      that provide relevant therapeutic guidance. A key impediment to this is the lack
      of understanding as to the function of such models. In order to improve this it
      is useful to recognise that musculoskeletal modelling is the mathematical
      description of musculoskeletal movement--a process that involves the construction
      and solution of equations of motion. These equations are derived from standard
      mechanical considerations and the mathematical representation of anatomy. The
      fidelity of musculoskeletal models is highly dependent on the assumption that
      such representations also describe the function of the musculoskeletal geometry.
      In addition, it is important to understand the sensitivity of such
      representations to patient-specific variations in anatomy. The exploration of
      these twin considerations will be fundamental to the creation of musculoskeletal
      modelling tools with clinical relevance and a systematic enquiry of these key
      parameters is recommended.

PMID- 22468466
TI  - Influence of joint models on lower-limb musculo-tendon forces and three
      dimensional joint reaction forces during gait.
AB  - Several three-dimensional (3D) lower-limb musculo-skeletal models have been
      developed for gait analysis and different hip, knee and ankle joint models have
      been considered in the literature. Conversely to the influence of the musculo
      tendon geometry, the influence of the joint models--i.e. number of degrees of
      freedom and passive joint moments--on the estimated musculo-tendon forces and 3D
      joint reaction forces has not been extensively examined. In this paper musculo
      tendon forces and 3D joint reaction forces have been estimated for one subject
      and one gait cycle with nine variations of a musculoskeletal model and outputs
      have been compared to measured electromyographic signals and knee joint contact
      forces. The model outputs are generally in line with the measured signals.
      However, the 3D joint reaction forces were higher than published values and the
      contact forces measured for the subject. The results of this study show that,
      with more degrees of freedom in the model, the musculo-tendon forces and the 3D
      joint reaction forces tend to increase but with some redistribution between the
      muscles. In addition, when taking into account passive joint moments, the 3D
      joint reaction forces tend to decrease during the stance phase and increase
      during the swing phase. Although further investigations are needed, a five-degree
      of-freedom lower-limb musculo-skeletal model with some angle-dependent joint
      coupling and stiffness seems to provide satisfactory musculo-tendon forces and 3D
      joint reaction forces.

PMID- 22468467
TI  - Muscle discretization affects the loading transferred to bones in lower-limb
      musculoskeletal models.
AB  - Modelling the mechanical effect of muscles is important in several research and
      clinical contexts. However, few studies have investigated the effect of different
      muscle discretizations from a mechanical standpoint. The present study evaluated
      the errors of a reduced discretization of the lower-limb muscles in reproducing
      the muscle loading transferred to bones. Skeletal geometries and a muscle data
      collection were derived from clinical images and dissection studies of two
      cadaver specimens. The guidelines of a general method previously proposed for a
      different anatomical district were followed. The data collection was used to
      calculate the mechanical effect of muscles, i.e. the generalized force vectors,
      and the errors between a large and a reduced discretization, in a reference
      skeletal pose and in the extreme poses of the range of motion of joints. The
      results showed that the errors committed using a reduced representation of
      muscles could be significant and higher than those reported for a different
      anatomical region. In particular, the calculated errors were found to be
      dependent on the individual anatomy and on the skeletal pose. Since different
      biomechanical applications may require different discretization levels, care is
      suggested in identifying the number of muscle lines of action to be used in
      musculoskeletal models.

PMID- 22468468
TI  - Determination of three-dimensional joint loading within the lower extremities in
      snowboarding.
AB  - In the biomechanical literature only a few studies are available focusing on the
      determination of joint loading within the lower extremities in snowboarding.
      These studies are limited to analysis in a restricted capture volume due to the
      use of optical video-based systems. To overcome this restriction the aim of the
      present study was to develop a method to determine net joint moments within the
      lower extremities in snowboarding for complete measurement runs. An experienced
      snowboarder performed several runs equipped with two custom-made force plates as
      well as a full-body inertial measurement system. A rigid, multi-segment model was
      developed to describe the motion and loads within the lower extremities. This
      model is based on an existing lower-body model and designed to be run by the
      OpenSim software package. Measured kinetic and kinematic data were imported into
      the OpenSim program and inverse dynamic calculations were performed. The results
      illustrate the potential of the developed method for the determination of joint
      loadings within the lower extremities for complete measurement runs in a real
      snowboarding environment. The calculated net joint moments of force are
      reasonable in comparison to the data presented in the literature. A good
      reliability of the method seems to be indicated by the low data variation between
      different turns. Due to the unknown accuracy of this method the application for
      inter-individual studies as well as studies of injury mechanisms may be limited.
      For intra-individual studies comparing different snowboarding techniques as well
      as different snowboard equipment the method seems to be beneficial. The validity
      of the method needs to be studied further.

PMID- 22468469
TI  - Maintaining case mix index in a post-ICD-10 world.

PMID- 22468470
TI  - An integrated patient accounting system.

PMID- 22468471
TI  - Strengthening your position for payer contract negotiations.

PMID- 22468472
TI  - [Instituto Nacional de Salud Publica. 25 years of postgraduate programs of
      excellence and public policy innovation].

PMID- 22468473
TI  - [Aging and chronic illness. Common pathways or parallel courses?].

PMID- 22468474
TI  - The importance of habitual vitamin A dietary intake on the serum retinol
      concentration in the elderly: a population-based study.
AB  - INTRODUCTION: The aging population is one of the main results of population
      demographic trends during the twentieth century and will be the hallmark of
      populations during this century. OBJECTIVE: To assess the habitual dietary
      vitamin A intake and serum retinol concentration in the elderly. MATERIAL AND
      METHODS: This is a population-based epidemiological study conducted in Joao
      Pessoa, Paraiba, northeastern Brazil, from July 2008 to January 2010, with 212
      individuals from 60 to 90 years of age, from both genders. Habitual food intake,
      retinolemia and C-reactive protein (CRP), as well as socioeconomic and
      anthropometric data were collected. RESULTS: The median of vitamin A intake was
      1643.40 microg EAR/day (p25 = 1112.20-p75 = 2430.80). The average serum retinol
      concentration was 1.91 +/- 0.68 mmol/L. There was no correlation of CRP
      concentration with serum retinol (r = 0.061/p = 0.424), nor with the habitual
      dietary retinol intake (r = 0.000/p = 0.932). However, there was a direct
      relationship between food intake and serum retinol concentration (r = 0.173/p =
      0.025). Only 3.98% (IC95% 6.88-1.08) of subjects had inadequate serum retinol
      concentrations 1.05 micromol/L), and 12.4% (IC95% 17.36-7.44) had inadequate
      vitamin A intake (< 625 microg for males and < 500 microg for females). Most
      individuals assessed in this study showed adequate retinolemia state and habitual
      dietary vitamin A intake, probably protecting them from this specific nutritional
      vulnerability, and no correlation between CRP concentration and serum and dietary
      retinol was found, possibly because these individuals had no acute inflammation
      and absence of chronic decompensated diseases.

PMID- 22468475
TI  - [Study of the vascular morphology of the lower limb nerves used as grafts].
AB  - INTRODUCTION: The placement of a vascularized nervous graft is an option for
      acute nervous injuries treatment, as this has demonstrated a longer viability.
      OBJECTIVE: To carry out a macroscopic and microscopic analysis of the vascularity
      of the main lower limb nerves used as vascularized nervous grafts. MATERIALS AND
      METHODS: It was followed out a descriptive, transversal and non-comparative study
      to analyse the saphenous, the sural, the deep peroneal and the superficial
      peroneal nerves vascularity. This study was performed in two stages: 1) an in
      situ vascularity study and 2) a morphometric study. RESULTS: By the in situ
      study, it was demonstrated the following: the total length of the lower limb
      nerves used as graft, was in a decrease order: sural nerve (micro = 29.26 cm, +/-
      4.05 cm), superficial peroneal nerve (micro = 28.61 cm, +/- 3.97 cm), deep
      peroneal nerve (micro = 26.64 cm, +/- 5.21 cm) and saphenous nerve (micro = 25.12
      cm, +/- 4.42 cm). The morphometric study demonstrated that the dominant artery
      with the major diameter belongs to the saphenous nerve, with a diameter of 1.13
      mm; then we have the superficial peroneal nerve with a 1.01 mm diameter, followed
      by the deep peroneal nerve with 0.91 mm, and finally the sural nerve with the
      smallest diameter, 0.85 mm. CONCLUSIONS: The saphenous nerve has the most
      appropriated morphological characteristics to be used as a vascularized graft; by
      the contrary the deep peroneal nerve represents the last option from all the
      nerves included in this study.

PMID- 22468477
TI  - [Association of childhood sexual abuse and disordered eating in a sample of
      Mexican adolescents].
AB  - OBJECTIVE: To analyze the association between childhood sexual abuse (CSA) and
      disordered eating (DE). MATERIAL AND METHODS: A probabilistic sample of 2,358
      female high school students of public schools in the Estado de Mexico was used.
      RESULTS: DE was more prevalent among CSA sufferers (p < or = 0.05). Preoccupation
      with gaining weight, binging and restrictive behaviors were associated to CSA (p
      < or = 0.05). The probability of DE was 7 times higher when the CSA experience
      had not been revealed and 36 times when CSA happened before 14 years of age.
      CONCLUSIONS: The association between CSA and DE is clear in the sample studied,
      as well as with some of its specific characteristics, which highlights the need
      to deepen in this research field and to incorporate the evaluation of CSA and its
      consequences in adolescents' mental health.

PMID- 22468476
TI  - [Nutrition iodine status in pregnant women in the sanitary district Sierra de
      Huelva-Andevalo, South of Spain].
AB  - BACKGROUND: Iodine is an essential trace element implicated in synthesis of
      thyroid hormones. Iodine requirements vary throughout life. This iodine
      requirement is increased during pregnancy and breastfeeding. In a previous study
      carried out by our group in 2008, we detected an iodine-deficient area in the
      province of Huelva, specially in district Sierra de Huelva-Andevalo by means of
      neonatal TSH determinations. OBJECTIVE: To reinforce the iodine supplementation
      campaign and its impact on their newborns in order to assess nutrition iodine
      status in pregnant women using questionnaire and ioduria determination. MATERIAL
      AND METHODS: This study has been jointly carried out by Congenital Hypothyroidism
      Unit of the Clinical Biochemistry Department of the Virgen Macarena University
      Hospital (Seville) and the Gynecology and Clinical Analysis Unit of the Rio Tinto
      Hospital (Huelva) during two years. We studied 313 pregnant women. All of them
      filled out a personal questionnaire to know the iodine nutritional status in
      their area. Ioduria was determinated by high-resolution liquid chromatography.
      Data from pregnant women and results of the studied variables were analyzed with
      SPSS v13.0. CONCLUSIONS: Pregnant women from the sanitary district Sierra de
      Huelva-Andevalo present a median for ioduria which corresponds to an insufficient
      iodine intake according to the WHO classification. The questionnaires suggest
      that this iodine deficiency is consequence of an insufficient iodine intake and a
      low adherence to the treatment.

PMID- 22468478
TI  - [Associated factors to extubation failure in the term newborns from a neonatal
      intensive care unit].
AB  - INTRODUCTION: The mechanical ventilator support (MVS) it is a procedure which
      improves survival of critically ill newborns (NB), but is not risk free one of
      them is tracheal damage reintubations by extubation failure. Knowledge that there
      is the medical literature is about preterm infant and there is not information
      about term NB. OBJECTIVE: To establish that factors are associated to the
      unsuccessful extubation in the term NB from 37 to 42 weeks of gestational age.
      MATERIAL AND METHODS: Retrospective study, of case-control in cohort including
      all the files and/or patient term NB that were interned in the Neonatal Intensive
      Care Unit of a Neonatology Service during the period of January from the 2004 to
      December of 2008 that they fulfilled the selection criteria. They were formed two
      groups: group A of cases (extubation failure) and group B of controls (successful
      extubation). Extubation failure was considered when there was need for the
      patient reintubate during first 72 hrs. We take into account to patient of term
      NB of one to 28 days of extrauterine life that remained with MVS at least 24 hrs
      and that to extubate was achieved with or without success, previous step for
      tracheal continuous positive airway pressure (CPAP), and that they were not more
      than 28 days with MVS. The statistical analysis was carried out by means of the
      descriptive and the inferential statistic. It was considered area of significance
      with p < 0.05. RESULTS: Fourty one patients were included divided in two groups:
      group A (cases) of 17 patients, and group B (controls) with 24 patients. The
      population's characteristics studied among the two groups didn't show significant
      differences. Of the variables studied between the two groups showed significant
      differences of age at start of ventilation, calories and the hemoglobin for
      controls and the time spent with MVS, reintubations number, and the peak
      inspiratory pressure (PIP) prior to the passage of the CPAP for cases, all with p
      < 0.05. In the multivariate analysis they were significant association as factor
      of risk for the extubation failure when the PIP was > 18 cm H2O, cycles > 15x'
      and hemoglobin < 13 g/dL. CONCLUSIONS: Based on the above we conclude that in the
      term NB with MVS before placing in tracheal CPAP for the extubation should have a
      PIP < or = 18 cm H2O, cycles < or = 15x' and a hemoglobin not smaller than 13
      g/dL to avoid this way as much as possible the extubation failure and with it to
      improve the prognosis.

PMID- 22468479
TI  - Overall survival of chronic myeloid leukemia patients treated with related donor
      hematopoietic stem cell transplant or imatinib.
AB  - OBJECTIVE: To determine the overall survival (OS) of Ph1 positive chronic myeloid
      leukemia (CML) patients treated with allogeneic hematopoietic stem cell
      transplant (AHSCT) vs. imatinib. MATERIAL AND METHODS: We retrospectively
      included CML patients treated with related donor myeolablative and non
      myeloablative AHSCT, between 1992 and 2009. Another group consisted of a patient
      cohort treated with imatinib between 2001 and 2009. The main variable was the
      persistence of hematologic remission. RESULTS: The AHSCT/ imatinib groups
      included 36/46 patients, average age was 36/46, patients in chronic phase 34/44
      and in blastic phase, 2/2. The number of myeloablative/non-myeloablative
      transplants was 28/8. Imatinib was administered at a dose of 400 to 800 mg/day
      (median 500 mg). The following events developed in both groups: death 14/3,
      hematological progression 4/5, 17/41 are alive and in hematological remission (p
      = 0.00009). The OS probability is 0.42 and 0.76 at 100 months (p = 0.0001). The
      decrease in absolute risk is 42%. The OS after 17 years remains unmodified in the
      AHSCT group after the first 6 years. CONCLUSION: OS at 100 months is superior
      with imatinib than with AHSCT (p = 0.0001).

PMID- 22468480
TI  - [Adolescents increase to more gestational weight and fat than adults according to
      BMI pre-gestational].
AB  - INTRODUCTION: The excessive gestational weight gain predisposes to overweight and
      obesity postpartum, this becomes a worldwide public health problem. OBJECTIVE: To
      analyze gestational weight pattern and body fat in adolescents and adult women,
      to identify the group that would have major weight and body fat gain. MATERIAL
      AND METHODS: A prospective cohort study done in 64 adolescent < or = 18 years and
      48 adult women. Anthropometric evaluation was realized, at 20, 24, 28, 32, 36 and
      38 gestational weeks with weight and body fat percentage. Patients signed letter
      informed consent. RESULTS: In adolescents weight and BMI were smaller (p <
      0.001), and their gestational fat gain was bigger than in the adult women (5.31
      vs. 4.12 kg; p < 0.001). Pre-gestational BMI (beta = 0.459, EE = 0.089, p =
      0.001), and age group (beta = - 1.400, EE = 0.735, p = 0.060) were associated to
      fat percentage variability. The adolescents with low weight and BMI > or = 85th
      percentile showed a greater gain of weight in respect to which is classified as
      normal weight (18.0 and 15.5 vs. 12.0 kg; p = 0.018). 54.7% of the adolescents
      and 64.6% of adults did gain excessive weight, more than the recommended
      according pre-gestational BMI. CONCLUSIONS: Age and pregestational BMI
      conditioned the body fat change. More than half of the patients included exceeded
      the recommended weight gain. The overweight or excessive weight gain adolescents
      have increased risk of postpartum retention weight than adult women in the same
      conditions.

PMID- 22468481
TI  - [Magnetoreception: the angular stone in aerospace orientation, human balance and
      locomotion].
AB  - Current research is in agreement with the presence of a magnetic compass in
      living beings including humans. The two most accepted explanations that
      demonstrate the existence of magnetoreceptors in living beings are, the radical
      pair and the biogenic magnetite, which are discussed here with its respective
      experimental evidence and support. It indicates the presence of magnetite
      crystals in otoliths, among different inferior species of animals. Moreover, the
      magnetite found in several organs of human body allows predicting the existence
      of such element, in otoliths of vestibular system as well; further, anticipates
      that human magnetoreception is an additional function of the vestibular system.
      These geomagnetic signals would modulate balance, movement and spatial
      positioning of man in concordance of gravity values. This new field of
      otomagnetism opens new research areas for understanding the mechanisms involved
      in balance, equilibrium, orientation, and space positioning in normal and disease
      populations. Likewise, this could be the starting point for application of new
      human neurorehabilitation procedures, in those magnetoreception-associated
      neurological disorders that happen in the earth, the sea or the air.

PMID- 22468482
TI  - [MicroRNAs in diagnosis and prognosis in lung cancer].
AB  - MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that regulate
      gene expression at the posttranscriptional level by blocking translation or
      inducing degradation of messenger RNA targets. It has been shown that miRNAs
      participate in a wide spectrum of essential biologic processes including cell
      cycle, differentiation, development, apoptosis and hematopoiesis, revealing one
      of the major regulators of human gene expression. Recent studies have shown
      evidences of abnormal expression of miRNAs in solid and hematological tumors, as
      well as the association of altered miRNAs with oncogenic or tumor suppressor
      functions, suggesting a key role of miRNAs in carcinogenesis. Moreover, unique
      profiles of altered miRNAs expression seem to allow distinction from normal
      tissue, prediction of disease outcomes, and evaluation of tumor aggressiveness in
      several types of cancer, including lung cancer. These unique and highly stable
      miRNAs patterns seems not to depend of age and race, and these characteristics
      highlight their potential diagnostic and prognosis utility. These findings are
      particularly promising for lung cancer, a worldwide leading cause of cancer
      related deaths with a poor survival rate, despite the discovery of novel
      therapies. This review describes the potential of miRNAs as biomarkers for
      diagnosis, cancer classification and estimation of prognosis in lung cancer; and
      the approaches used to detect and quantify these miRNAs; including the current
      information about circulating miRNAs as potential biomarkers in lung cancer. This
      review also provides a description of miRNAs biogenesis, nomenclature and
      available database for miRNA sequences.

PMID- 22468483
TI  - [Rituximab: a new therapeutic alternative in Grave's disease].
AB  - Graves' disease is the most frequent cause of hyperthyroidism, affecting mainly
      young aged women, with an etiology of autoimmune basis. One of its
      manifestations, Graves' ophthalmopathy whose pathophysiology is unknown,
      represents one of the greatest therapeutic challenges in these patients, because
      they require aggressive treatment with steroids and multiple subsequent
      reconstructive surgeries in certain cases. It also represents a high burden to
      the health system. Drugs targeting B cells have been very effective for many
      autoimmune diseases. Rituximab is a murine humanized monoclonal antibody against
      CD20 + cells currently being studied in various autoimmune diseases including
      Graves' disease. The objective of this paper is to expose possible mechanisms by
      which rituximab could act in both hyperthyroidism and ophthalmopathy of Graves'
      disease, as well as the experience with its use acquired so far. The employment
      of rituximab in recently diagnosed patients or with mild ophthalmopathy is
      questionable with the evidence available today however, we think that it may have
      a role in refractory cases or those who have a contraindication for steroid use.

PMID- 22468484
TI  - [Genomic analysis and amino acid gene ompA of Chlamydia trachomatis serotype F
      isolated in Mexico].

PMID- 22468485
TI  - [Vaccination for influenza AH1N1 in health-care workers at the intensive care
      unit].

PMID- 22468486
TI  - [Lugala is the last domino piece].

PMID- 22468487
TI  - [Globalization and mental health. Uprooted and disillusioned].

PMID- 22468488
TI  - [Manifesto for health workforce crisis. Against the fatal "care drain" ].

PMID- 22468489
TI  - [Mentally ill parents. Not forgetting the children].

PMID- 22468490
TI  - [Titlis model. Closing gaps in drug management].

PMID- 22468491
TI  - [Geriatric day and night clinic. Preventing errors means improving the system].

PMID- 22468492
TI  - [Geriatric psychiatry. Nursing interventions in sleep disorders].

PMID- 22468493
TI  - [Rehabilitation nursing. "... nothing is as it was once"].

PMID- 22468494
TI  - [Photo exhibit. "Nursing worlds" in the shopping world].

PMID- 22468495
TI  - [Interdisciplinary management. Cancer after-care is a team responsibility].

PMID- 22468496
TI  - [Chimeric futures].

PMID- 22468497
TI  - [Parenting and attachment. The baby, the object that disturbs].

PMID- 22468498
TI  - [Transition from curative nursing care to palliative nursing care. Barriers and
      nursing interventions].

PMID- 22468499
TI  - [Analysis and integrated changes. A practice serving all].

PMID- 22468500
TI  - [Mental handicap and communication difficulties. For personalized hospitalization
      and more serenity].

PMID- 22468501
TI  - ["Bottled life". Control over water].

PMID- 22468502
TI  - [A system causing madness. Land of refuge].

PMID- 22468503
TI  - [A "hors sol" society].

PMID- 22468504
TI  - [Study on control and management for industrial volatile organic compounds (VOCs)
      in China].
AB  - Volatile organic compounds (VOCs) emitted from industrial sources account for a
      large percent of total anthropogenic VOCs. In this paper, VOCs emission
      characterization, control technologies and management were discussed. VOCs from
      industrial emissions were characterized by high intensity, wide range and uneven
      distribution, which focused on Bejing-Tianjin Joint Belt, Shangdong Peninsula,
      Yangtze River Delta and the Pearl River Delta. The current technologies for VOCs
      treatment include adsorption, catalytic combustion, bio-degradation and others,
      which were applied in petrochemical, oil vapor recovery, shipbuilding, printing,
      pharmaceutical, feather manufacturing and so on. The scarcity of related
      regulations/standards plus ineffective supervision make the VOCs management
      difficult. Therefore, it is suggested that VOCs treatment be firstly performed
      from key areas and industries, and then carried out step by step. By establishing
      of actual reducing amount control system and more detailed VOCs emission
      standards and regulations, applying practical technologies together with
      demonstration projects, and setting up VOCs emission registration and
      classification-related-charge system, VOCs could be reduced effectively.

PMID- 22468505
TI  - [Countermeasures for priority control of toxic VOC pollution].
AB  - VOC pollution is worsening, not only affects the environment, air quality, but
      also directly harm human health, and Chinese relevant departments need to improve
      control measures. U. S. toxic air pollutants (HAPs) control system was studied,
      and Chinese environment countermeasures were proposed based on pollution
      features. U. S. recognized sources of hazardous air pollutants in the Clean Air
      Act (CAA), and reduced their emissions by industrial regulations and regional
      policies. In urban areas, VOC occupied a great part of toxic air and were
      controlled as a major project in U. S. Due to relatively weak management and
      technical base, China should screen some VOC components for priority pollutant
      control. The feature of Chinese VOC pollution was described as complex
      components, industry sources widely distributed, strong regional characteristics
      and processes, and gradual development of regional pollution. It was suggested to
      carry out investigation assessment activities, enhance cumulative risk assessment
      and environmental impact assessment management, and strengthen emergency risk
      prevention.

PMID- 22468506
TI  - [Evaluation of treatment technology of volatile organic compounds for fixed
      industrial resources].
AB  - The reduction of the emission of volatile organic compounds (VOCs) from fixed
      industrial resources is considered more necessary than before. The traditional
      treatment techniques, newly developed ones and some combinations of these
      treatment techniques are reviewed in this paper. The applying conditions,
      developing trend and existing problems of these techniques are also evaluated.

PMID- 22468507
TI  - [Emission control way of volatile organic compounds in industry].
AB  - Due to the volatile nature, the way of controlling way of VOCs was different from
      other atmospheric pollutants. By analyzing the emission characteristics of VOCs,
      four kinds of control way were proposed, which were the source control, organized
      emission control, fugitive emission control and the total amount control, and the
      control modes of each control way were also analyzed and compared.

PMID- 22468508
TI  - [Regulations and policies for control of volatile organic compounds and the
      emission standards in Taiwan].
AB  - Due to the well-developed managing system including policies, laws, regulations
      and emission standards, now the emission of volatile organic compounds (VOCs) is
      strictly controlled in Taiwai. The policy frameworks of VOCs control including
      both command control and economic incentives makes an excellent effect for VOCs
      treatment.

PMID- 22468509
TI  - [Study on foreign regulations and standards of stationary sources VOCs emission
      control].
AB  - By investigating volatile organic compounds (VOCs) emission control regulations
      and standards of the United States, the European Union and Japan, the suggestions
      on VOCs emission control and standards formulating in China were presented.
      Referencing foreign successful environmental management approach and experience,
      as well as the corresponding regulations and standards, the author believed that
      China can find a simple and highly effective way for controlling VOCs, through
      establishing the emission standards system, innovating VOCs emission control
      approach, improving VOCs emission control efficiency and unifying VOCs monitoring
      methods.

PMID- 22468510
TI  - [VOCs tax policy on China's economy development].
AB  - In this paper, environmental tax was designed to control volatile organic
      compounds (VOCs) emissions. Computable general equilibrium (CGE) model was used
      to explore the impacts of environmental tax (in forms of indirect tax) on the
      macro-economy development at both national and sector levels. Different levels of
      tax were simulated to find out the proper tax rate. It is found out that imposing
      environmental tax on high emission sectors can cause the emission decreased
      immediately and can lead to negative impacts on macro-economy indicators, such as
      GDP (gross domestic products), total investment, total product and the whole
      consumption etc. However, only the government income increased. In addition, the
      higher the tax rate is, the more pollutants can be reduced and the worse economic
      effects can be caused. Consequently, it is suggested that, the main controlling
      policies of VOCs abatement should be mandatory orders, and low environmental tax
      can be implemented as a supplementary.

PMID- 22468511
TI  - [Characteristics of volatile organic compounds (VOCs) emitted from biofuel
      combustion in China].
AB  - Biofuel combustion is an important source of VOCs in China. Measurements were
      conducted to determine the characteristics of VOCs emitted from combustion of 5
      typical biofuels. A carbon mass balance method was used to determine VOCs
      emission factors. The emission factors of the total VOCs from agricultural
      residues and wood combustion are (4.37 +/- 2.23) g x kg(-1) and (2.12 +/- 0.77) g
      x kg(-1), respectively. The emission factors of the agricultural residues are
      higher than those of the wood. Aromatics and aldehydes dominate the VOC
      emissions, both accounting for over 25% of the total VOC emissions. Distribution
      of VOC components from agricultural residues and wood combustion are similar,
      except for halogenated hydrocarbons and nitriles. On the basis of measured
      emission factors and the published maximum incremental reactivity values for
      VOCs, the ozone forming potential (OFPs) of speciated VOCs is estimated. The
      results indicate that the average OFPs of the total VOCs from agricultural
      residues and wood combustion are (16.9 +/- 8.2) g x kg(-1) and (10.8 +/- 4.9) g x
      kg(-1), respectively. The components with the highest OFPs values are: aldehydes,
      aromatics and alkenes/alkynes. Aldehydes accounts for over 50% of the total OFPs.

PMID- 22468512
TI  - [Spatial and temporal variations of ambient carbonyl compounds in Beijing and its
      surrounding areas].
AB  - Concentrations of 23 carbonyl compounds were measured by DNPH/HPLC method at 38
      sites within Beijing and its surrounding areas on June 24, July 22, August 22,
      September 14 in 2010 and January 13, 2011. The average mixing ratios of total
      carbonyl compounds in Beijing were (16.38 +/- 6.03) x 10(-9) and (8.50 +/- 5.27)
      x 10(-9) in summer and winter; and the average mixing ratios in surrounding cites
      were (13.19 +/- 5.71) x 10(-9) and (13.05 +/- 2.44) x 10(-9) in summer and
      winter, respectively. The most abundant carbonyl compound was formaldehyde,
      followed by acetaldehyde and acetone, the sum of these 3 species accounted for
      78% to 91% of the total mixing ratio of carbonyl compounds. The average mixing
      ratio in summer was significant higher than that in winter, and higher in morning
      (09:00-12:00) hours than in afternoon (13:00-16:00). The spatial distributions
      for carbonyl compounds showed that: in summer, high mixing ratios were typically
      found in city center; while in winter, a building-up trend was found from
      northwest to southeast, driving by the prevailing northwest wind. In summer,
      vehicular exhaust had important contributions to ambient carbonyls, and combined
      with the adverse weather conditions and the strong photochemical production,
      resulted in carbonyls pollutions; in winter, directly emissions were the main
      sources of carbonyls, such as vehicular exhaust and coal burning.

PMID- 22468513
TI  - [Analysis on status pollution and variation of BTEX in Beijing].
AB  - In order to study the pollution status and the seasonal and diurnal variations,
      ambient concentrations of BTEX were analyzed at Beijing from 2008-10 to 2009-10,
      by using the method of two-step-concentration-gas spectrometry/mass (CCD-GC/MS).
      The average concentration of BTEX in Beijing was 13.9-44.0 microg x cm(-3). The
      dominant compound components were toluene, benzene, followed by ethyl benzene,
      m/p-xylene, o-xylene. Compared with foreign cities and regions, the level of BTEX
      at Beijing atmosphere was relatively lower. The study found that BTEX in Beijing
      mainly came from vehicle emissions, coal and solvent evaporation were also
      important sources of BTEX. No significantly obvious seasonal variation was
      observed, with the highest concentrations observed in spring and summer and the
      lowest concentrations generally found in autumn. Seasonal variations of emission
      sources were the main reason for seasonal changes of BTEX. However, the impact of
      weather factors on the BTEX can not be ignored, such as temperature and strong
      winds. Significant diurnal variations in BTEX were observed. The BTEX
      concentrations displayed a bimodal pattern, with peak between 08:00 and 10:00.
      and between 16:00 and 08:00. The minimum concentration generally appeared around
      14:00.

PMID- 22468514
TI  - [Characteristics of ambient VOCs and their role in O3 formation: a typical air
      pollution episode in Shanghai urban area].
AB  - The concentration, speciation and chemical reactivity of ambient volatile organic
      compounds (VOCs) in shanghai city were analyzed and measured by using online gas
      chromatography with flame ionization detection systems (GC-FID) during a typical
      air pollution episode (from Oct. 30th to Nov. 2nd, 2010) and 55 kinds of VOCs
      were detected. The results show that averaged concentrations of VOCs was 27 x 10(
      9) before the episode, and then dramatically increased by 3 times (87 x 10(-9))
      in the episode than the former, the main components were alkanes (35.2 x 10(-9)),
      aromatics (30.0 x 10(-9)), alkenes (21.6 x 10(-9)). Furthermore, the maximum
      ozone formation potential (PhiOFP) is analyzed and showed that PhiOFP (in the
      episode) > PhiOFP (after the episode) PhiOFP (before the episode). Before the
      episode, the percent of PhiOFP for aromatics 53.0% , alkenes 36. 1% and alkanes
      11.7%; in the episode, the percent of PhiOFP for aromatics 54.7%, alkenes 36.7%
      and alkanes 9.8%; after the episode, the percent of PhiOFP for alkenes 52.7%,
      aromatics 36.0% and alkanes 13.2%. Alkenes (C2-C4) and aromatics (C6-C8) are the
      main components for the ozone formation, namely toluene, m,p-xylene, 1,3
      butadiene, propene, ethene et al. In addition, the relationship is negative and
      nonlinear between the O3 and PhiOFP. And efficiencies of PhiOFP formed into O3
      are below 20. 0% in different stage of episode. This is very important and
      meaningful for the quantitative evaluate the influence of VOCs towards O3.

PMID- 22468515
TI  - [Observation and study on atmospheric VOCs in Changsha city].
AB  - Volatile organic compounds (VOCs) are one of the key precursors of atmospheric
      ozone (O3), which also contribute to the production of SOA. During 2008, VOCs
      were measured near Changsha City. Weekly integrated canister samples were
      collected and analyzed in the morning and afternoon of each Tuesday.
      Simultaneously, concentration, potential ozone production and sources of VOCs in
      the atmosphere of Changsha were studied. The results indicated that the total
      VOCs species had higher concentrations in the morning (38.4 x 10(-9)), and lower
      in the afternoon (22.7 x 10(-9)), where the concentration of halo carbon was the
      highest, and alkanes, aromatics and alkenes came next. The m/p-xylene had the
      highest OH reactivity concentration (10.71 x 10(-9) C), 1,2,4-trimethylbenzene
      (6.04 x 10(-9) C) and 1,3,5-trimethylbenzene (2.23 x 10(-9) C) came next.
      Aromatics (66%) had the most significant contribution to the production of O3 in
      the atmospheric VOCs of Changsha, and alkenes (26%) and alkanes (8%) came next.
      The highest concentrations of propane and isopentane indicated vehicular exhaust
      and liquefied petroleum gas (LPG) appear to be the main source of VOCs in
      Changsha City. Benzene/toluene ratio was higher than 0.5 which was close to 0.8,
      showing solvent volatilization was also a main source of VOCs.

PMID- 22468516
TI  - [Characteristics of volatile organic compounds during haze episode in Foshan
      city].
AB  - Volatile Organic Compounds (VOCs) in Foshan City were investigated in December 6
      to 30 2008. The concentrations of VOCs in haze days were significantly higher
      than those in no-haze days. Toluene (68.93 microg x m(-3) +/- 37.78 microg x m(
      3)) was the most abundant compound of VOCs in haze days and i-pentane (20.59
      microg x m(-3) +/- 14.28 microg x m(-3)) was the most abundant compound in no
      haze days, respectively. During haze episodes, the diurnal variations of alkanes
      and alkynes were not significantly; however, alkenes and aromatic hydrocarbon
      decreased significantly at noon. During no-haze episodes, the diurnal variations
      patterns of VOCs were stable. Propylene-equivalent concentrations in haze days
      were significantly higher than those in no-haze days, toluene was the most
      abundant compound of Propylene-equivalent concentration in haze days, followed by
      propene and ethene; propene was the most abundant compound in no-haze days,
      followed by ethene and 1-butene. High concentration of benzene (18.1 microg x m(
      3)) in haze days posed a great health threat to public in Foshan city. Both
      diurnal variation of VOCs and measured ratios indicated vehicular emissions acted
      as the main sources of most VOCs and other sources like solvent application also
      contributed to VOCs (benzene and toluene).

PMID- 22468517
TI  - [Investigation on emission properties of biogenic VOCs of landscape plants in
      Shenzhen].
AB  - Isoprene and monoterpene emissions were characterized using flow and enclosure
      sampling method and GC-MS in USA for 158 species of plants growing in Shenzhen,
      China. This survey was designed to include all of the dominant plants within the
      Shenzhen region as well as unique plants such as Cycads. These are the first
      measurements in a subtropical Asian metropolis. Substantial isoprene emissions
      were observed from thirty-one species, including Caryota mitis, Adenanthera
      pavonina var. microsperma, Mangifera indica and Excoecoria agalloch. Monoterpene
      emissions were observed from fifty-two species, including Passiflora edulis,
      Bambusa glaucescens cv. silverstripe as well as some primitive and rare
      Cycadaceae and Cyatheaceae plants. For the first time some of red plants have
      been measured, most of them have the ability of releasing terpene. These results
      will be used to develop biogenic emission model estimates for Shenzhen and the
      surrounding region that can be used as inputs for regional air quality models.

PMID- 22468518
TI  - [Pollution and source of atmospheric volatile organic compounds in urban-rural
      juncture belt area in Beijing].
AB  - A method for determining volatile organic compounds (VOCs) by cryogenic dynamic
      adsorption in solid adsorbent tubes, subsequent thermal desorption with
      cryofocusing in a cold trap and analysis by gas chromatography and mass
      spectrometry was adapted. Volatile organic content levels, spatial and temporal
      distribution and sources were studied. Results indicated that 265 species were
      detected in atmospheric environment of this area, including alkanes, alkenes,
      aromatics, halohydrocarbons and oxygenated compounds. The average concentration
      of VOCs is 431.7 microg x m(-3), followed by aromatics 248.1 microg x m(-3),
      alkanes 130.5 microg x m(-3) alkenes 11.7 microg x m(-3), halohydrocarbons 22.4
      microg x m(-3), oxygenated compounds 18.6 microg x m(-3), respectively. Benzene,
      toluene, ethylbenzene, xylene and so on have a comparatively high content.
      Aromatics and alkanes are the most abundant VOCs; Organic pollutants generally
      occurred at a relatively high level in the morning and evening traffic rush
      hours. VOCs varied with seasons: winter maximum, followed by autumn, summer
      minimum. Source analysis showed that atmospheric VOCs mainly come from vehicular
      exhaust, gasoline evaporation, use of adhesive and solvent and vegetation
      emission. They accounted for 53.4%, 20.1%, 11.0% and 5.93%, respectively.

PMID- 22468519
TI  - [Health risk assessment of atmospheric volatile organic compounds in urban-rural
      juncture belt area].
AB  - A method for determining volatile organic compounds (VOCs) by cryogenic dynamic
      adsorption in solid adsorbent tubes, subsequent thermal desorption with
      cryofocusing in a cold trap and analysis by gas chromatography and mass
      spectrometry was adapted. An internationally recognized four-step evaluation
      model of health risk assessment (HRA) was adapted to preliminarily assess the
      health risks caused by volatile organic compounds (VOCs) in urban-rural juncture
      belt area in Beijing. Results of HRA indicated that non-carcinogenic risk indexes
      of VOCs are below 1 and non-carcinogenic risk indexes of aromatic substances
      range from 10(-4)-10(-5), halohydrocarbons in the 10(-4)-10(-1). Volatile
      pollutants would not cause non-carcinogenic health hazard to exposed population.
      However, the cancer risk index exposed to carcinogenic benzene was 2.21 x 10(-5),
      which is higher than that suggested value of USEPA (1x10(-6)) and may cause
      potential harm to human health. The greatest health risk is in winter, followed
      by autumn, summer minimum.

PMID- 22468520
TI  - [Source emission characteristics of malodorous volatile organic carbonyls from a
      municipal sewage treatment plant].
AB  - A 4-day field observation was conducted at Liede sewage treatment plant in
      Guangzhou, using PFPH/GC/MS method to analyse the composition and the
      concentration of volatile carbonyl compounds, and investigate the source emission
      characteristics of the pollutants. The results were as follows: 18 carbonyl
      species were detected, which including 15 malodorous volatile carbonyls with a
      concentration range from 0.39 microg x m(-3) to 19.92 microg x m(-3) at six
      processing units. Mean value of the total malodorous volatile carbonyls was
      (68.66 +/- 10.05) microg x m(-3). Normalization data process was used to research
      the source emission profile for malodorous volatile carbonyls, formaldehyde,
      acetaldehyde, propionaldehyde, 2-butanone, butyraldehyde and hexaldehyde were
      found to be molecular markers of the source emission with their percentage of
      total carbonyls up to 78.91%. Hexaldehyde was the most abundant carbonyl species
      with an average concentration of 11.71 microg x m(-3). Using a calculation model
      of area source emission, it estimated that the total annual emissions of the
      municipal sewage treatment plant was 2 302.33 kg(-1), and the contribution ratio
      of each processing unit was in an order of biochemical reaction basin,
      concentration basin, grade A aeration, ascending pump room, grit basin,
      dewatering house. The malodorous emission of sewage treatment plant is affected
      by many complex factors, so there's some uncertainty on the estimate.

PMID- 22468521
TI  - [Source emission characteristics and impact factors of volatile halogenated
      organic compounds from wastewater treatment plant].
AB  - A low enrichment method of using Tenax as absorbent and liquid nitrogen as
      refrigerant has been established to sample the volatile halogenated organic
      compounds in Guangzhou Liede municipal wastewater treatment plant as well as its
      ambient air. The composition and concentration of target halogenated hydrocarbons
      were analyzed by combined thermal desorption/GC-MS to explore its sources profile
      and impact factors. The result showed that 19 halogenated organic compounds were
      detected, including 11 halogenated alkanets, 3 halogenated alkenes, 3 halogenated
      aromatic hydrocarbons and 2 haloesters, with their total concentrations ranged
      from 34.91 microg x m(-3) to 127.74 microg x m(-3) and mean concentrations ranged
      from n.d. to 33.39 microg x m(-3). Main pollutants of the studied plant were
      CH2Cl2, CHCl3, CFC-12, C2H4Cl2, CFC-11, C2HCl3 and C2Cl4, they came from the
      wastewater by volatilization. Among the six processing units, the dehydration
      room showed the highest level of halogenated organic compounds, followed by
      pumping station, while the sludge thickener was the lowest. The emissions from
      pumping station, aeration tank and biochemical pool were significantly affected
      by temperature and humidity of environment.

PMID- 22468522
TI  - [Quantification assessment of the relationship between chemical and olfactory
      concentrations for malodorous volatile organic compounds].
AB  - Using self-made cold-traps and gas bags, the odor samples were collected from 6
      sewage treatment workshops of a typical municipal sewage treatment plant in
      Guangzhou City. The chemical composition and olfactory concentrations of these
      samples were respectively analyzed by thermal-desorption/GC-MS and triangle odor
      bag method. Finally, a mathematical equation was built for assessing the
      relationship between principal organic odorants and the olfactory concentrations.
      The result showing that: (1) More than 70 volatile organic compounds were
      detected in municipal sewage treatment plant, among which were 30 malodorous
      volatile organic compounds (MVOCs), ranging from 0.37 to 1 872.24 microg x m(-3)
      and appearing in sludge dewatering, thickening and aeration tank with the highest
      concentrations. (2) Principle component analysis was used to group the target
      MVOCs into 5 categories: benzenes, halohydrocarbons, aldehydes, hydrocarbons and
      S, N-containing organic compounds. (3) Multiple lineal regression analysis was
      used to build a quantified relationship between chemical and olfactory
      concentrations of MVOCs. The result indicated that 25% of the odor problem of
      sewage treatment unit was due to MVOCs. The predicted values were fitting well
      with measured values. The sensitivity of mathematical equation for measuring odor
      concentration was higher than that of human olfactory system.

PMID- 22468523
TI  - [Study on transformation mechanism of SOA from biogenic VOC under UV-B
      condition].
AB  - A laboratory study was carried out to investigate the biogenic volatile organic
      compounds (BVOC) in a lab-made glass chamber. The secondary organic aerosol (SOA)
      products can be detected under the UV photooxidation of BVOC. Pelargonium x
      Citrenella was chosen as the target plant in this research because it can release
      a large amount of BVOCs. The predominant 7 alkene and ketol compounds were
      detected by using solid phase microextraction (SPME) sampling and gas
      chromatography/mass spectrometry (GC/MS) analysis. The photochemical experiment
      indicated that these BVOC can be rapidly oxidized into SOA under UV-B
      irradiation. A tandem differential mobility analyzer (TDMA) was used to measure
      the size distribution and the hygroscopicity of the SOA. The particle diameter
      was in the range of 50 nm to 320 nm. The high hygroscopicity of SOA was also
      obtained and the size increased from 1.05 to 1.11 during the wet experiment.

PMID- 22468524
TI  - [Kinetic studies on the gas-phase reactions of NO3 radicals with three cyclic
      ethers].
AB  - Kinetics of the reaction of NO3 radicals with tetrahydrofuran, 1, 3-dioxolane and
      1, 4-dioxane at 298 K +/- 1 K and 1.01 x 10(5) Pa were investigated using a
      relative rate method in a self-made Teflon chamber. The objective of this study
      was to assess the possible impact of these volatile organic compounds (VOCs) on
      the environment by studying their atmospheric degradation kinetics. Using gas
      chromatograph with a flame ionization detector(GC/FID), the measured reaction
      rate constant for NO3 with tetrahydrofuran was (5.36 +/- 1.93) x 10(-3) cm
      (molecule x s)(-1), which is in good agreement with the reported values,
      indicating the reliability of our experiment setup and methods. The reactions of
      NO3 radicals with 1, 3-dioxolane and 1, 4-dioxane were studied for the first time
      and the measured rate constants were (1.84 +/- 0.70) x 10(-15) cm3 x (molecule x
      s)(-1) and (3.20 +/- 0.67) x 10(16) cm3 x (molecule x s)(-1), respectively. The
      atmospheric lifetimes of these compounds have also been estimated based on the
      measured rate constants, which indicate that emissions of these compounds may
      have an impact on regional atmospheric environment.

PMID- 22468525
TI  - [Uptake of 3-methyl-3-buten-1-ol into aqueous mixed solution of sulfuric acid and
      hydrogen peroxide].
AB  - Multiphase acid-catalyzed oxidation with hydrogen peroxide (H2O2) has been
      suggested recently to be a potential route to SOA formation, but the kinetics and
      chemical mechanism of this process have not been well-known yet. In this work,
      the uptake of 3-methyl-3-buten-1-ol (MBO331) into aqueous mixed solutions of
      H2O2, and sulfuric acid (H2SO4) was performed using a rotated wetted-wall reactor
      coupled to a VUV single-photon ionization time of flight mass spectrometer (VUV
      SPI-TOFMS). The reactive uptake coefficients (gamma) were acquired for the first
      time and the reaction pathways were deduced according to products information.
      The uptake of MBO331 into H2SO4/H2O2 was fast, resulting in gamma reaching 2.52 x
      10(-4)-1.05 x 10(-2) for 40%-60% H2SO4. Acetaldehyde, acetone and 3-methyl-3, 4
      expoxybutane-1-ol were suggested as gas-phase products in this process. 3-methyl
      3,4-expoxybutane-1-ol can transform into polyhydroxy compounds while the further
      reactions of the carbonyl products can occur in acidic solution, which may play a
      role in SOA formation. Thus, the heterogeneous acid-catalyzed oxidation of MBO331
      with H2O2 might be a significant contributor to SOA loading.

PMID- 22468526
TI  - [An overview on analytical method of volatile organic compounds in water].
AB  - Various methods on monitoring of volatile organic compounds in water in domestic
      environmental monitoring field were overviewed recently. In order to better
      understand the advantages and characteristics of various instruments, such as
      laboratory, emergency, and automatic on-line instrument, analytical methods of
      volatile organic compounds in water were reviewed and evaluated through specific
      instruments and experiments. This will enable these methods to play a more
      effective role for future research.

PMID- 22468527
TI  - [Determination of low concentration VOCs in air by a newly designed needle trap
      device].
AB  - Targeting on the problem of atmospheric VOCs that are presenting low
      concentration and difficult for sampling, a newly designed needle trap device
      with carboxen 1000 as a sorbent material was developed. The main advantages of
      needle trap device are the simple methodology,the easiness and the rapidity of
      the analysis coupling with GC-MS. No solvent was used in all experiments.
      Volatile analytes benzene, toluene, ethylbenzene and xylenes (BTEX) were chosen
      as target compounds to validate this device from theory to real application. The
      experimental parameters as breakthrough volume of stripping gas were
      investigated. LOD ranges was obtained at 0.05 ng x mL(-1), and the standard
      recovery was from 86.5% to 110.5% respectively. Needle trap device is suitable
      for sampling in field.

PMID- 22468528
TI  - [Research on determination of total volatile organic sulfur compounds in the
      atmosphere].
AB  - A detection technology was established comprising trap, desorption, oxidation and
      UV fluorescence determination process, and used for the test of total
      concentration of trace volatile sulfur compounds (VSCs) in the atmosphere. A
      cryogenic trap-thermal desorption device was developed, integrating the
      advantages of solid retention method and cryogenic condensation method, which was
      applied to capture and enrich trace volatile organic sulfur compounds. Under high
      temperature and combustion-supporting gas, the VSCs were completely oxidized into
      sulfur dioxide. By analyzing the content of sulfur dioxide through ultraviolet
      fluorescence method indirectly calculated to gain the total concentration of
      volatile organic sulfur compounds. The trapping temperature, desorption
      temperature and the oxidation temperature were 5 degrees C, 150 degrees C and 1
      000 degrees C, and the precision and recovery of the method were 5.46% and 99.6%
      109.2%, respectively. The content of trace amounts of atmospheric VSCs determined
      from February to April at Qingdao was 42-195 ng x m(-3).

PMID- 22468529
TI  - [Automatic continuous monitoring of volatile organic compounds using ion mobility
      spectrometer array].
AB  - An ion mobility spectrometer array was designed, in order to broaden the
      detection range of ion mobility spectrometer and improve the accuracy of compound
      identification. This instrument was based on the combination of ionization
      sources of 63Ni positive ion mode, 63Ni negative ion mode and photoionization
      mode with vacuum UV lamp, and it can continuously monitor the volatile organic
      compounds in air. With the automatic system of sampling and injection of this
      instrument, the positive ion of dimethyl sulfoxide and negative ion of
      dichloromethane were detected simultaneously. By comprehensive analysis of
      spectra with ion mobility spectrometer array, acrylonitrile, m-xylene and acetone
      were identified, which were difficult to be distinguished under the 63Ni positive
      ion mode. Acetone samples were determined quantitatively within four days
      continuously, and the results indicated that the linear range of acetone in this
      instrument was 2 orders of magnitude. The linear correlation coefficient R was
      higher than 0.995, and the relative standard deviations were controlled in the
      range of 4.0%-18.3%. Methacrylate leaked in simulation was monitored on-line for
      24 h continuously, using the method of dynamic tracking, and the result showed
      the leaking time and the concentration of methacrylate directly.

PMID- 22468530
TI  - [Development of a membrane inlet-single photon ionization/chemical ionization
      mass spectrometer for online analysis of VOCs in water].
AB  - A home-made membrane inlet- single photon ionization/chemical ionization- time-of
      flight mass spectrometer has been described. A vacuum ultraviolet (VUV) lamp with
      photon energy of 10.6 eV was used as the light source for single photon
      ionization (SPI). Chemical ionization (CI) was achieved through ion-molecule
      reactions with O2- reactant ions generated by photoelectron ionization. The two
      ionization modes could be rapidly switched by adjusting electric field in the
      ionization region within 2 s. Membrane inlet system used for rapid enrichment of
      volatile organic compounds (VOCs) in water was constructed by using a
      polydimethylsiloxane (PDMS) membrane with a thickness of 50 microm. A purge gas
      was added to accelerate desorption of analytes from the membrane surface. The
      purge gas could also help to prevent the pump oil back-streaming into the
      ionization region from the analyzer chamber and improve the signal to noise ratio
      (S/N). Achieved detection limits were 2 microg x L(-1) for methyl tert-butyl
      ether (MTBE) in SPI mode and 1 microg x L(-1) for chloroform in SPI-CI mode
      within 10 s analysis time, respectively. The instrument has been successfully
      applied to the rapid analysis of MTBE in simulated underground water nearby
      petrol station and VOCs in disinfected drinking water. The results indicate that
      the instrument has a great application prospect for online analysis of VOCs in
      water.

PMID- 22468531
TI  - [Detection of TVOC and odor in industrial park using electronic nose].
AB  - The main volatile compounds belong to TVOC or odor which may generate from
      industrial park,special sensors were adopted to build electronic nose for
      detecting those compounds. TVOC pollution index (TPI) and odor pollution index
      (OPI) were designed as well as detecting method based on electronic nose in the
      field. On this basis, considering the pollution situation of chemical industrial
      of Zhapu port in Jiaxing, six detecting points were selected to be tested by
      electronic nose on site. Each sensor responses processed by principal components
      analysis (PCA), two principal components were extracted, that is, eight sensors
      can be divided into two groups including the types of TVOC (S1) and odor (S2-S8).
      Meanwhile, the on site collected samples were qualitatively analyzed with GC/ MS.
      At each testing point, integral area percentage of the compounds being a part of
      TVOC accumulated mostly over 90% and to odor, mostly was below 10%. Results show:
      (1) Choosing appropriate sensors combining PCA can preliminarily reflect the
      pollution condition of TVOC and odor in industrial park; (2) Combining pollution
      indexes measured with electronic nose and results of qualitative analysis with
      GC/MS can generally concluded the overall pollution situation of TVOC and odor in
      industrial park and distribution of each pollutant; (3) Application of electronic
      noses and GIS to detect TVOC and odor in industrial park can preliminary assess
      space pollution situation in industrial park.

PMID- 22468532
TI  - [Applicability of an electronic nose for detection of volatile chlorinated
      hydrocarbons in soil].
AB  - An electronic nose principally composed of a photo ionization detector (PID) was
      developed for rapid detection of volatile chlorinated hydrocarbons (VCHs) in
      contaminated soil. Removal of interference gas such as benzene homologues with a
      pre-filtration tube was analyzed with gas chromatography (GC). A standard gas
      generator was applied to generate different concentrations of perchloroethylene
      (PCE) and trichloroethylene (TCE) gas, with which the determine precision and
      reproducibility of the electronic nose were evaluated by comparison with GC.
      Finally, simulated contamination soil with three typical paddy soils in Yangtze
      river delta region were used for ventilation purification experiments, the change
      of VCHs concentrations in the ventilation gas was monitored, based on which the
      applicability of the electronic nose was evaluated for on-line detection of the
      on-going of the ventilation purification process. Results showed that a
      halogenated hydrocarbon RAE-SEP tube was effective to remove interference gas,
      with 80%-97% of benzene homologues such as benzene and ethyl benzene being
      removed while more than 90% of VCHs passed through. With PCE or TCE gas, a linear
      dependence was derived between the data determined with the electronic nose and
      GC, the linear slope being 1.012 and R2 > 0.99. The electronic nose showed data
      consistent with GC (R2 > 0.99, n = 47) when applied for monitoring the
      remediation progress in a soil ventilation process. The electronic nose is
      therefore possibly applicable for rapid determination of soil pollution by VCHs,
      improving the efficiency of pollution diagnosis and remediation.

PMID- 22468533
TI  - [Test and analysis of acrylic acid ester in industry pipelines].
AB  - A new quality and quantity analyzing method for waste gas from chemical industry,
      especially for acrylic acid ester using air-sampling combined with GC/MS and
      honeywell air purifier system was firstly advanced in this paper. According to
      the experiments, the maximum disposal capability of the honeywell air purifier
      system for acrylic acid ester gas was calculated as about 1 kg x h(-1) and the
      feasibility and validity of the method was also proved by parallel tests.

PMID- 22468534
TI  - [Preparation of honeycombed monolithic zeolite and hydrophobic modification with
      SiCl4].
AB  - A kind of hydrophobic zeolitic monolith were prepared by mixing HY/ZSM-5,
      additives and water, followed by processes of extrusion and drying, and then
      hydrophobic modification with SiCl4. The structures and properties of the
      adsorbent were examined by nitrogen adsorption and desorption measurement, XRD,
      and benzene adsorption experiment. The results show that those adsorbents possess
      hierarchical pore structures and excellent hydrophobicity.

PMID- 22468535
TI  - [Synthesis of manganese oxide octahedral molecular sieve and their application in
      catalytic oxidation of benzene].
AB  - Manganese oxide octahedral molecular sieves (OMS-2) for VOCs catalytic combustion
      were synthesized by refluxing method. The crystal structure, particle morphology,
      pore structure and H2-reduction ability were characterized by XRD, SEM, N2
      adsorption-desorption and H2-TPR techniques. The catalytic activities of the OMS
      2 calcined at different temperatures in benzene combustion and the stability of
      the sample calcined at 300 degrees C were evaluated. The results indicated that
      the effect of calcinations temperature on the surface characters of catalysts was
      remarkable. With higher calcination temperature, the samples showed lower surface
      area and pore volume, but larger average pore size. At the same time, high
      calcination temperature leaded to low activity. The benzene conversion of the
      sample calcined at 300 degrees C was 50% degrees C at 200 degrees C and 90% at
      250 degrees C, respectively. The catalytic activity exhibited only 5% reduction
      after reaction at 260 degrees C for 70 h, which indicated that the as-made
      catalysts were very stable after calcination at 300 degrees C.

PMID- 22468536
TI  - [Adsorption-desorption performance of honeycomb-shaped activated carbon].
AB  - Honeycomb-shaped activated carbon is useful to control organic gas pollution of
      large air-flow and low concentration. Effects of adsorbents, toluene
      concentration, velocity of empty bed and temperature of desorption on its
      adsorption-desorption performance were studied by conducting on dynamic
      experiments. Results shown that adsorption properties of honeycomb-shaped
      activated carbon were increased with decreasing of the inlet toluene
      concentration under the condition of certain outlet toluene concentration, and
      gas velocity of empty bed was recommend as 1.2-1.8 m x s(-1). With increasing of
      the desorption temperature, the outlet toluene concentration appeared peak-value
      and fluctuated widely, and the recommended desorption temperature was 90 degrees
      C. Gas velocity of empty bed affected the peak value of concentration of the
      toluene, and practical value was 0.2-0.4 m x s(-1).

PMID- 22468537
TI  - [Process of adsorption and separating recovery solvents from vapor mixture
      directly].
AB  - Experiment on process feasibility of adsorption and separating recovery of
      organic compounds directly from waste gas was conducted with the activated carbon
      column train consists of 4 units in serial. Isopropyl alcohol and toluene vapor
      mixture was used as target gas, which are the common constituents of the gas
      emitted from fine ceramic manufacture. The experimental results showed obvious
      adsorption stratification phenomena alone the activated carbon column length for
      the vapor mixture. Under the condition of superficial gas velocity of 0.42 m x s(
      1), inlet concentration of 477 mg x m(-3) and 746 mg x m(-3) for isopropyl
      alcohol and toluene respectively, 26 cm total carbon packing length of the four
      column serial train, when the adsorption time reached 798 min, the adsorption
      capacities for toluene and isopropyl alcohol are 184.5 mg x g(-1) and 0 mg x g(
      1) respectively in 0-10 cm section, and 0.92 mg x g(-1) and 91.2 mg x g(-1)
      respectively in 21-26 cm section, liquids with over 99% purity of isopropyl
      alcohol and toluene were recovered separately from the two end columns of the
      carbon column train. There is a gaseous concentration amplifier zone in the
      carbon column for the weaker adsorbate, isopropyl alcohol, which make the
      adsorption capacity of isopropyl alcohol increase over 27% in part of the down
      flow zone in this experiment. It is possible to directly recover the pure solvent
      liquid separately from the vapor mixture by the way of a serial adsorption column
      with separating stage recovering.

PMID- 22468538
TI  - [BTF performance treating a chlorobenzene-contaminated gas stream].
AB  - In this study, biotrickling filter (BTF) inoculated with acclimated sludge was
      established to treat waste gas containing chlorobenzene. The BTF performance,
      average well color development (AWCD) values and microbial community were
      examined in steady state. Results revealed BTF achieved removal efficiency more
      than 80% of chlorobenzene under the conditions of < 0.6 g x m(-3) inlet
      concentration and > 45 s EBRT. Therefore, BTF have an advantage in treating low
      concentration waste gas containing chlorobenzene (< or = 0.6 g x m(-3)). The
      overall chlorobenzene elimination capacity reached a maximum of 70 g x (m3 x h)(
      1) at an inlet load of 80 g x (m3 x h)(-1). The mass ratio of carbon dioxide
      produced to the BTo-X removed was approximately 1.92, which confirms complete
      degradation of chlorobenzene, given that some of the organic carbon consumed is
      also used for the microbial growth. The degradation of chlorobenzene in the BTF
      followed Michaelis-Menten kinetic model, the maximum specific degradation rate
      (r(max)) was 35.6 g x (m3 x h)(-1). The AWCD values indicated that the
      microorganisms in the BTF showed high the microbial metabolic activity. The PCR
      DGGE fingerprinting analysis on biofilm samples in the BTF indicated that the
      microbial community had a relative stability and complexity during the steady
      state phase. The stability and complexity of microbial community could contribute
      to the degradation and mineralization of chlorobenzene in BTF.

PMID- 22468540
TI  - [Analysis of the treatment technology pathway of VOCs released from oven].
AB  - Treatment of VOCs from oven of container production process is taken as an
      example to discuss the characteristics of regenerative thermo oxidation (RTO)
      heat recovery technology and activated carbon adsorption-steam desorption-solvent
      recovery technology, based on a large number of data gathered in many projects.
      It is suggested that, both of technologies are able to achieve the purpose of
      recovery VOCs; Compared with activated carbon adsorption-steam desorption-solvent
      recovery technology, RTO-heat recovery technology has better economic and
      environmental benefit.

PMID- 22468539
TI  - [Purification of complicated industrial organic waste gas by complex absorption].
AB  - Complicated industrial organic waste gas with the characteristics of low
      concentration,high wind volume containing inorganic dust and oil was employed the
      research object by complex absorption. Complex absorption mechanism, process
      flow, purification equipment and engineering application were studied. Three
      different surfactants were prepared for the composite absorbent to purify exhaust
      gas loaded with toluene and butyl acetate, respectively. Results show that the
      low surface tension of the composite absorbent can improve the removal efficiency
      of toluene and butyl acetate. With the advantages of the water film, swirl plate
      and fill absorption device, efficient absorption equipment was developed for the
      treatment of complicated industrial organic waste gas. It is with superiorities
      of simple structure, small size, anti-jam and high mass transfer. Based on
      absorption technology, waste gas treatment process integrated with heating
      stripping, burning and anaerobic and other processes, so that emissions of waste
      gas and absorption solution could meet the discharge standards. The technology
      has been put into practice, such as manufacturing and spraying enterprises.

PMID- 22468541
TI  - [Fabrication of Co3O4 nanorods and its catalytic oxidation of gaseous toluene].
AB  - Co3O4 nanorods were fabricated by the low-temperature hydrothermal method. The
      Co3O4 nanorods were formed through adding a small amount of surfactants
      (Polyvinylpyrrolidone, referred to as PVP) and reacting at 95 degrees C.
      Controlling the reaction time of preparation and pH of the solution can affect
      the properties of Co3O4 nanorods. X-ray diffraction (XRD), transmission electron
      microscopy (TEM) proved the as-prepared samples were Co3O4 nanorods in cubic
      phase. Hydrogen temperature programmed reduction (H2-TPR) and nitrogen adsorption
      desorption experiment results showed that the size and pore structure of Co3O4
      nanorods could be affected by different reaction time and pH, and led to the
      difference in specific surface area. The catalytic properties of Co3O4 nanorods
      were examined by degradation of gaseous toluene. The results showed that
      conversion of toluene was affected under low temperature by Co3O4 nanorods, which
      were prepared by different reaction time and pH. When the temperature was below
      260 degrees C, the catalyst prepared in alkaline condition had the highest
      activity. However, when the temperature was higher than 260 degrees C, the
      conversion of toluene was hot significantly different.

PMID- 22468542
TI  - [Preparation, characterization of Si doped TiO2 nanotubes and its application in
      photocatalytic oxidation of VOCs].
AB  - The Si-doped TiO2 nanotubes photocatalysts was synthesized by anodic oxidation
      method, which used Na2SiF6/HF as an electrolyte, and was characterized by means
      of SEM, XRD, DRS and EDX. TiO2 nanotubes composed of anatase phase and rutile
      phase, and Si was highly dispersed on the wall of TiO2 nanotubes. The
      photocatalytic activity of the Si-doped TiO2 nanotubes was investigated for
      photocatalytic degradation of gaseous toluene. It was found that the
      photocatalytic activity of Si-doped TiO2 nanotubes, which prepared by 0.03 mol x
      L x (-1) Na2SiF6/HF and calcined at 400 degrees C for 1 h, was the highest. The
      conversion of toluene was 60% over the prepared Si doped TiO2 nanotubes under UV
      light, which was one times higher than that of pure TiO2 nanotubes.

PMID- 22468543
TI  - [Research of the natural attenuation capacity of oil pollutants based on in-situ
      experiment].
AB  - Based on the results of the in-situ experiment carried out in a Beijing gas
      station, the ways of natural attenuation were evaluated as both aerobic and
      anaerobic biodegradation via oxygen and carbon equilibrium calculation. And the
      research got the rates of the natural attenuation and half-life of the oil
      pollutants byusing the first-order decay model. Based on the analysis, the
      capability of monitored natural attenuation and the environmental quality were
      evaluated. The results show that the actual oxygen consumption of contaminated
      site is less than that needed theoretically in aerobic degradation of all
      pollutants, while the amount of CO2 detected is far less than that in the aerobic
      degradation by theoretical formation. And the half-life of petroleum contaminants
      in contaminated site is about 50 days. The analysis indicated that: (1) The ways
      of natural attenuation were proved as both aerobic and anaerobic biodegradation;
      (2) The contamination of the BTEX tested by the fist-step experiment fell below
      the environmental standard level after about 250 days' natural attenuation, which
      means the environmental risk in this gas station had been eliminated and the
      control measures could be removed.

PMID- 22468544
TI  - [Experimental research of oil vapor pollution control for gas station with
      membrane separation technology].
AB  - Two kinds of membranes modules, vapor retained glassy membrane based on PEEK
      hollow fiber membrane modules and vapor permeated rubbery membrane system based
      on GMT plate-and-frame membrane modules, were used to control the oil vapor
      pollution during the course of receiving and transferring gasoline in oil
      station. The efficiencies of the membrane module and the membrane system of them
      were evaluated and compared respectively in the facilities which were developed
      by ourselves. It was found that both the two kinds of membranes modules had high
      efficiency for the separation of VOCs-air mixed gases, and the outlet vapor after
      treatment all can meet the national standard. When the vapor-enriched gas was
      returned to the oil tank to simulate the continuously cycle test, the
      concentration of VOCs in the outlet was also below 25 g x m(-3).

PMID- 22468545
TI  - [CFD numerical simulation onto the gas-liquid two-phase flow behavior during
      vehicle refueling process].
AB  - With the gradual improvement of environmental regulations, more and more
      attentions are attracted to the vapor emissions during the process of vehicle
      refueling. Research onto the vehicle refueling process by means of numerical
      simulation has been executed abroad since 1990s, while as it has never been
      involved so far domestically. Through reasonable simplification about the
      physical system of "Nozzle + filler pipe + gasoline storage tank + vent pipe" for
      vehicle refueling, and by means of volume of fluid (VOF) model for gas-liquid two
      phase flow and Re-Normalization Group kappa-epsilon turbulence flow model
      provided in commercial computational fluid dynamics (CFD) software Fluent, this
      paper determined the proper mesh discretization scheme and applied the proper
      boundary conditions based on the Gambit software, then established the reasonable
      numerical simulation model for the gas-liquid two-phase flow during the refueling
      process. Through discussing the influence of refueling velocity on the static
      pressure of vent space in gasoline tank, the back-flowing phenomenon has been
      revealed in this paper. It has been demonstrated that, the more the flow rate and
      the refueling velocity of refueling nozzle is, the higher the gross static
      pressure in the vent space of gasoline tank. In the meanwhile, the variation of
      static pressure in the vent space of gasoline tank can be categorized into three
      obvious stages. When the refueling flow rate becomes higher, the back-flowing
      phenomenon of liquid gasoline can sometimes be induced in the head section of
      filler pipe, thus making the gasoline nozzle pre-shut-off. Totally speaking, the
      theoretical work accomplished in this paper laid some solid foundation for self
      researching and self-developing the technology and apparatus for the vehicle
      refueling and refueling emissions control domestically.

PMID- 22468546
TI  - On the estimation of survival and death probabilities under myocardial
      infarctions in the presence of competing risks based on an illness-death model.
AB  - This paper is concerned with the development of an illness-death model for the
      study of survivability of heart patients. The Myocardial Infarctions (MI)
      experienced in heart disease have been categorized as fatal and nonfatal. Fatal
      MI's are easily recognizable and identified and are always reported in the case
      history of the patient suffering from heart disease whereas non-fatal MI's are
      not easily identified and are rarely reported in the case history of the patient.
      Also, in the case of human population, all individuals are not equally healthy
      and the chance of dying varies from one person to another. Moreover illness and
      death are two different types of events. Illness may be transient, repetitive and
      reversible, whereas death is an irreversible or absorbing state. Further
      complexity is introduced by competition among various risks of death. The
      probability of an individual dying from one cause is influenced by the presence
      of competition from other causes. Here in our problem we have taken two health
      states viz. normal state and illness state due to non-fatal MI's, and two death
      states viz. death state due to fatal MI and death state due to competing risk.
      The study population of n individuals is divided into two groups viz. n1
      individuals who are in the normal state and n2 individuals who are in the illness
      state due to non-fatal MI's, at the time of start of the study. The expressions
      for survival and death probabilities have been obtained by using the concep of
      crude probability of death under competing risks. The likelihood estimates of the
      survival and death probabilities have also been obtained. Application of the
      model is discussed.

PMID- 22468547
TI  - Phenotypic detection of constitutive and inducible clindamycin resistance in
      clinical isolates of Staphylococcus aureus and coagulase negative Staphylococcus
      on routine susceptibility plate.
AB  - Increasing frequency of methicillin resistant Staphylococcus aureus infections
      and changing patterns in antimicrobial resistance have led to renewed interest in
      the use of macrolidelincosamide-streptogramin antibiotics. However therapy may
      fail either due to constitutive or inducible resistance. This study was
      undertaken to detect different phenotypes including inducible clindamycin
      resistance in clinical isolates of Staphylococcus aureus and coagulase negative
      Staphylococcus. Four hundred sixty five Staphylococcus aureus and 84 coagulase
      negative Staphylococci isolated from different clinical specimens were included
      in the study. On routine susceptibility testing plate clindamycin (2 microg) disk
      was placed at a distance of 15mm towards the centre from a peripherally placed
      erythromycin (15 microg) disk. Fisher exact test was used for statistical
      analysis. Out of 465 Staphylococcus aureus isolates, 237 (50.96%) were
      methicillin sensitive (MSSA) and 228 (49.03%) methicillin resistant
      (MLS(B)c).Over all 118 (25.37%) isolates showed constitutive resistance
      (MLS(B)c), 70 (15.05%) inducible clindamycin resistance, 143 (30.75%) MS(B)
      phenotype and 134 (28.81%) were susceptible to both erythromycin as well as
      clindamycin. Constitutive and inducible resistance to clindamycin were
      significantly higher in MRSA than MSSA (P=0.0000 and 0.0001 respectively). Out of
      84 isolates of coagulase negative Staphylococci, 43 (51.19%) were methicillin
      sensitive (MSCNS) and 41(48.80%) methicillin resistant (MRCNS). Constitutive
      MLS(B) resistance was detected in 32 (38.09%), inducible clindamycin resistance
      10 (11.90%), MS(B) phenotype 27 (32.14%) and 15 (17.85%) were susceptible to both
      erythromycin and clindamycin. Performing D test on a routine susceptibility plate
      saves material, manpower and time as inducible resistance can be reported
      simultaneously along with other susceptibility results.

PMID- 22468548
TI  - A study on the resting preference of mosquito species in wells in Vellore in
      Tamilnadu, South India.
AB  - The resting preferences of mosquito species was investigated in domestic wells.
      In addition to the routine adult surveys in human dwellings, adult collections
      were also made in domestic wells using an innovated equipment operating on the
      principles of spray sheet collections. Above the water surface, wells provide
      humid and dark microclimate along the inner walls. It has been observed that this
      microclimate provides very congenial resting place for few mosquito species;
      specially for the males and for the females between their gonotropic cycles.
      Larval collections in the wells did not reveal breeding of majority of the
      mosquito species collected by this technique. Investigations were conducted in 87
      wells in 11 localities during 2005. A total of 4969 mosquitos were collected of
      which 69.1% (3441) were males and 30.9% (1528) were females. From among the
      mosquitos collected 96.5% were Cu. quinquifasciatus, 0.26% All stephensi, 3.0%
      Aedes agypti and 0.24% Armegeres sp. The results of the analysis of the physical
      and chemical parameter of water samples of the study wells before and after the
      surveys endorsed the utility of this technique for entomological investigations
      in outbreak situations, for monitoring the liquidation of outbreak foci and for
      other research purposes.

PMID- 22468549
TI  - Lymphatic filariasis in East District, Sikkim.
AB  - East district of Sikkim has been considered as non-endemic for lymphatic
      filariasis (LF). However, a LF survey conducted during 2008 revealed microfilaria
      rate (mf rate) of 1.2%. The LF survey was carried out in 15 randomly selected
      villages and urban localities of East Sikkim. Out of 3,428 night blood smears
      collected and examined, 42 were found positive for Wuchereria bancrofti.
      Microfilaria (mf) carriers were detected from 5 surveyed villages and 5 urban
      localities of Singtam and Rangpoo with mf rate ranging from 0.5% to 4.2%. The
      mean mf density was 5.4 per 20cmm3 blood. All mf carriers were residents of east
      district, Sikkim except two persons who were from Bihar. The detection of
      microfilaria in young children who had never moved from the area indicates
      probable indigenous transmission. Out of 15 surveyed areas LF disease was found
      in 11 areas with prevalence ranging from 0.4% to 7.0%.(Disease rate was 1.6%)
      (1.7% for Males & 1.4% for females). One local individual was found with
      lymphoedema and also mf positive. Vector density ranged from 70 to 435 per ten
      man-hours, sufficient for transmission of LF. 712 female Cx. quinquefasciatus
      were dissected to detect the filarial infection and none was found positive. The
      present survey findings indicate endemicity of filariasis in East district of
      Sikkim.

PMID- 22468550
TI  - Study of biomedical waste management practices in a private hospital and
      evaluation of the benefits after implementing remedial measures for the same.
AB  - A study has been carried out to ascertain, whether biomedical Waste generated in
      private hospitals being segregated and managed properly? The study was carried
      out in a private tertiary care 620 bedded hospital located in an urban area in
      Delhi, India to assess the awareness and attitude of the hospital staff, to
      document the ongoing practices, enlisting the deficiencies, to identify the root
      causes and to suggest remedial measures for proper biomedical waste management
      and assess the benefits of implementing them. A process flow chart was made of
      the existing waste system of the hospital. An anonymous questionnaire survey was
      conducted to determine the awareness about the policies and practices. A training
      programme was organised and a manual for waste management was made and
      distributed in the hospital. The quantum of waste generated per day in the
      hospital was 610 kg with 150 kg being biomedical waste. It was observed that
      although the waste generated was being disinfected properly before disposal the
      hospital staff was not segregating the waste properly, with delays in lifting of
      waste compounded with improper disposal. The hospital has its own incinerator but
      it was underutilized. After the remedial measures including training and
      distribution of manuals, an improvement was found in the segregation process
      resulting in decrease in amount of infectious waste load to 50%. The survey shows
      that no appropriate strategy exists and there is an urgent need to increase
      awareness about rules, regulations and procedures regarding this vital issue.

PMID- 22468552
TI  - Impact of health education and condom distribution on incidence of RTI/STI among
      the newly married urban poor women in Delhi.
AB  - This study was carried out to find out the impact of a specially designed
      preventive intervention on menstrual and sexual hygiene practices and incidence
      of RTI/STI among the newly married women. A community based intervention study
      with controls was conducted in two resettlement colonies of Delhi. Total 74
      subjects in intervention group and 71 subjects in the control group were studied.
      Each subject was followed up for 9 months every three monthly. The intervention
      package included education about menstrual and sexual hygiene, RTI/STIs and
      contraceptive usage, and packets of condoms. RTI/STI was diagnosed using
      syndromic approach. Only 2 and 8 subjects in the intervention and control group
      respectively used condoms (p>0.05 after adjustment). Practice of washing genitals
      improved in the intervention group (p<0.05 both with and without adjustment). 19
      (25.68%) women in intervention and 22 (30.99%) in the control group (p=0.478)
      reported RTI/STI symptoms during study period; after adjusting for other
      variables OR=0.37 (p=0.007). 57.89% of RTI/STI patients consulted doctor in
      intervention group as compared to 18.18% in control group (p<0.05). Increasing
      awareness and providing intervention at the very beginning of sexual life of
      newly married women can modify some of the high risk behaviors and thus reduce
      the risk of acquiring RTI/STIs.

PMID- 22468551
TI  - A study on treatment outcome of registered tuberculosis cases under RNTCP in
      Udupi Taluk, Karnataka.
AB  - Directly Observed Treatment Short Course is the internationally recommended
      strategy to ensure cure of tuberculosis. However, it is equally important to
      review the shortcomings if any of such an important strategy against tuberculosis
      to make it more useful. This Descriptive study carried in a Tuberculosis Unit was
      to find out the treatment outcome of patients registered under Revised National
      Tuberculosis Control Program. The data was collected from the tuberculosis
      register and was analyzed using SPSS 13.0 version. Study included 563 patients,
      68% were males and 32.0% were females. Category I had majority of the patients
      307 (54.52%); Category II had 133 (23.6%), and Category III had 116 (20.6%)
      patients. In Category I, 175 (57.0%) patients were cured and 13(4.2%) had
      treatment failure. In Category II, 61 (45.9%) were cured and 11(8.3%) had
      treatment failure. In Category III, 105 (90.5%) had complet treatment. Out of 236
      patients who were cured, majority were under the care of government health
      workers 125(53%), followed by anganwadi 32(13.6%) and social workers 27(11.4%).
      Joint efforts of DOTS providers cured 53 (22.4%) patients. Ensuring early
      diagnosis and high cure rate of Tuberculosis cases is the only effective way to
      stop the spread of Tuberculosis.

PMID- 22468553
TI  - Antibiotic resistance pattern of urinary tract isolates of Escherichia coli from
      Kumaun region.
AB  - Concurrent resistance to antimicrobials of different classes has arisen in a
      multitude of bacterial species and may complicate the therapeutic management of
      infections, including those of the urinary tract. To assess the resistance
      pattern among urinary isolates of E. coli, the most prevalent pathogen
      contributing these infections, a retrospective in vitro surveillance study was
      carried out in the Department of Microbiology, Uttarakhand Forest Hospital Trust
      Medical College from Jan. 2006 - Dec. 2006. A total of 175 E. coli isolates from
      urinary specimen had been tested against 12 antimicrobials. E. coli isolates
      tested, 94.29% showed resistance to ampicillin, 92% to amoxycillin- salbactam,
      70.86% to gentamicin, 65.71% to amikacin, 89.71% to cefuroxime, 78.51% to
      cefotaxime,76% to cefriaxone, 90.28% to ciprofloxacin, 61.14% to chlormphenicol,
      46.28% to nitrofurantoin, 28% to piperacillin-tazobactam and 8.5% to imipenum.
      Multidrug resistance was defined as resistance to three or more classes of
      antibiotics. Multidrug resistance was detected in 97% isolates. These findings
      call for wiser use of antimicrobial agents and their continuous in vitro
      monitoring.

PMID- 22468554
TI  - Adherence to universal work precautions: a study among nurses and laboratory
      technicians in a teaching hospital of North India.

PMID- 22468555
TI  - Insecticides susceptibility studies of mosquito larvae from Mandya District,
      Karnataka State.

PMID- 22468556
TI  - Potential risk of dengue/DHF transmission in a selected locality of NCT town
      Gurgaon, Haryana, India.

PMID- 22468557
TI  - Sero-epidemiological investigation of an outbreak of fever in rural area of
      Rohtak.

PMID- 22468558
TI  - C-H bond strengths and acidities in aromatic systems: effects of nitrogen
      incorporation in mono-, di-, and triazines.
AB  - The negative ion chemistry of five azine molecules has been investigated using
      the combined experimental techniques of negative ion photoelectron spectroscopy
      to obtain electron affinities (EA) and tandem flowing afterglow-selected ion tube
      (FA-SIFT) mass spectrometry to obtain deprotonation enthalpies
      (Delta(acid)H(298)). The measured Delta(acid)H(298) for the most acidic site of
      each azine species is combined with the EA of the corresponding radical in a
      thermochemical cycle to determine the corresponding C-H bond dissociation energy
      (BDE). The site-specific C-H BDE values of pyridine, 1,2-diazine, 1,3-diazine,
      1,4-diazine, and 1,3,5-triazine are 110.4 +/- 2.0, 111.3 +/- 0.7, 113.4 +/- 0.7,
      107.5 +/- 0.4, and 107.8 +/- 0.7 kcal mol(-1), respectively. The application of
      complementary experimental methods, along with quantum chemical calculations, to
      a series of nitrogen-substituted azines sheds light on the influence of nitrogen
      atom substitution on the strength of C-H bonds in six-membered rings.

PMID- 22468559
TI  - Crystal and electronic structure and magnetic properties of divalent europium
      perovskite oxides EuMO3 (M = Ti, Zr, and Hf): experimental and first-principles
      approaches.
AB  - A comparative study of the crystal and electronic structure and magnetism of
      divalent europium perovskite oxides EuMO(3) (M = Ti, Zr, and Hf) has been
      performed on the basis of both experimental and theoretical approaches playing
      complementary roles. The compounds were synthesized via solid-state reactions.
      EuZrO(3) and EuHfO(3) have an orthorhombic structure with a space group Pbnm at
      room temperature contrary to EuTiO(3), which is cubic at room temperature. The
      optical band gaps of EuZrO(3) and EuHfO(3) are found to be about 2.4 and 2.7 eV,
      respectively, much larger than that of EuTiO(3) (0.8 eV). On the other hand, the
      present compounds exhibit similar magnetic properties characterized by
      paramagnetic-antiferromagnetic transitions at around 5 K, spin flop at moderate
      magnetic fields lower than 1 T, and the antiferromagnetic nearest-neighbor and
      ferromagnetic next-nearest-neighbor exchange interactions. First-principles
      calculations based on a hybrid Hartree-Fock density functional approach yield
      lattice constants, band gaps, and magnetic interactions in good agreement with
      those obtained experimentally. The band gap excitations are assigned to
      electronic transitions from the Eu 4f to Mnd states for EuMO(3) (M = Ti, Zr, and
      Hf and n = 3, 4, and 5, respectively).

PMID- 22468560
TI  - Disorder-to-order transition of an intrinsically disordered region of sortase
      revealed by multiscale enhanced sampling.
AB  - Molecular functions of intrinsically disordered proteins (IDPs) or intrinsically
      disordered regions (IDRs), such as molecular recognition and cellular signaling,
      are ascribed to dynamic changes in the conformational space in response to
      binding of target molecules. Sortase, a transpeptitase in Gram-positive bacteria,
      has an IDR in a loop which undergoes a disordered-to-ordered transition (called
      "disordered loop"), accompanying a tilt of another loop ("dynamic loop"), upon
      binding of a signal peptide and a calcium ion. In this study, all-atom
      conformational ensembles of sortase were calculated for the four different
      binding states (with/without the peptide and with/without a calcium ion) by the
      multiscale enhanced sampling (MSES) simulation to examine how the binding of the
      peptide and/or calcium influences the conformational ensemble. The MSES is a
      multiscale and multicopy simulation method that allows an enhanced sampling of
      the all-atom model of large proteins including explicit solvent. A 100 ns MSES
      simulation of the ligand-free sortase using 20 replicas (in total 2 MUs)
      demonstrated large flexibility in both the disordered and dynamic loops; however,
      their distributions were not random but had a clear preference which populates
      the N-terminal part of the disordered loop near the bound form. The MSES
      simulations of the three binding states clarified the allosteric mechanism of
      sortase: the N- and C-terminal parts of the disordered loop undergo a disorder-to
      order transition independently of each other upon binding of the peptide and a
      calcium ion, respectively; however, upon binding of both ligands, the two parts
      work cooperatively to stabilize the bound peptide.

PMID- 22468563
TI  - Substance use coping as a mediator of the relationship between trauma symptoms
      and substance use consequences among incarcerated females with childhood sexual
      abuse histories.
AB  - Rates of substance use and maltreatment are alarmingly high among incarcerated
      women. Although the direct link between trauma and substance use has been
      established, less is known about potential mediators. Thus, we examined substance
      use coping as a mediator between trauma symptoms and substance use consequences
      among a sample of incarcerated females (N = 111) who were survivors of childhood
      sexual abuse. Trauma symptoms predicted the severity of substance use
      consequences, with this relationship being mediated fully by avoidance coping
      (e.g., using substances to cope). Overall, trauma histories are important in
      predicting outcomes but must be examined in the context of current coping
      behaviors and substance use. Findings (data collected in 2007/2008) may help
      promote interventions that target patterns of coping and/or emotional avoidance
      among trauma survivors with substance use problems in incarcerated populations.
      The study's limitations are noted.

PMID- 22468564
TI  - Lab-on-a-bubble surface enhanced Raman indirect immunoassay for cholera.
AB  - We describe a novel sandwich assay based on surface enhanced Raman scattering
      (SERS) comprised of buoyant silica microspheres coated with antibodies against
      the beta subunit of the cholera toxin (CT), and gold nanoparticles tagged with a
      Raman reporter, shelled with silica and coated with antibodies against the beta
      subunit of the CT. Together these components couple to form a sandwich which,
      after incubation, floats on the surface of the sample. The buoyant silica
      microparticle/nanoparticle reporter combination has been coined a lab on a bubble
      (LoB). LoB materials may provide a platform for rapid detection of antigen in
      solution and offers advantages over lateral flow or magnetic pull-down assays.
      The Raman reporter provides a unique and intense signal to indicate a positive
      analysis. Our limit of detection for the beta subunit of the CT in a buffer based
      system is 1100 ng.

PMID- 22468565
TI  - Children's sensitivity to the knowledge expressed in pedagogical and
      nonpedagogical contexts.
AB  - The present studies test 2 hypotheses: (1) that pedagogical contexts especially
      convey generic information (Csibra & Gergely, 2009) and (2) that young children
      are sensitive to this aspect of pedagogy. We examined generic language (e.g.,
      "Elephants live in Africa") in 3 studies, focusing on informational versus
      narrative children's books (Study 1), the language of 6-year-old children and
      adults assuming either a pedagogical (teacher) or nonpedagogical (friend) role
      (Study 2), and the language of 5-year-old children and adults speaking to either
      an ignorant alien (pedagogical context) or a peer (nonpedagogical context; Study
      3). Results suggest that generics are more frequent in informational than
      narrative texts. Furthermore, both adults and young children provide more generic
      language in pedagogical contexts and when assuming a pedagogical role. Together,
      the studies demonstrate that pedagogical contexts are distinctive in conveying
      generic information and that children are sensitive to this aspect of the
      language input. We suggest that generic knowledge is more useful in making
      predictions about the future and thus more highly valued during instruction.

PMID- 22468566
TI  - Gendered motivational processes affecting high school mathematics participation,
      educational aspirations, and career plans: a comparison of samples from
      Australia, Canada, and the United States.
AB  - In this international, longitudinal study, we explored gender differences in, and
      gendered relationships among, math-related motivations emphasized in the Eccles
      (Parsons) et al. (1983) expectancy-value framework, high school math
      participation, educational aspirations, and career plans. Participants were from
      Australia, Canada, and the United States (Ns = 358, 471, 418, respectively) in
      Grades 9/10 at Time 1 and Grades 11/12 at Time 2. The 3 samples came from
      suburban middle to upper-middle socioeconomic backgrounds, primarily of Anglo
      European descent. Multivariate analyses of variance revealed stereotypic gender
      differences in educational and occupational outcomes only among the Australian
      sample. Multigroup structural equation models identified latent mean differences
      where male adolescents held higher intrinsic value for math in the Australian
      sample and higher ability/success expectancy in both North American samples.
      Ability/success expectancy was a key predictor in the North American samples, in
      contrast to intrinsic value in the Australian sample. Attainment/utility
      ("importance") values were more important for female adolescents' career choices,
      except in the Australian sample. Findings are interpreted in relation to gender
      socialization practices, degree and type of early choice, and specialization
      across settings. Implications are discussed for long-term math engagement and
      career selection for female and male adolescents. (PsycINFO Database Record (c)
      2012 APA, all rights reserved).

PMID- 22468567
TI  - An assessment of the validity of the ECERS-R with implications for measures of
      child care quality and relations to child development.
AB  - The Early Childhood Environment Rating Scale-Revised (ECERS-R) is widely used to
      associate child care quality with child development, but its validity for this
      purpose is not well established. We examined the validity of the ECERS-R using
      the multidimensional Rasch partial credit model (PCM), factor analyses, and
      regression analyses with data from the Early Childhood Longitudinal Study Birth
      Cohort. The PCM identified rating category disordering, indicating previously
      unrecognized problems with the scale's response process validity. Factor analyses
      identified neither a single factor nor the ECERS-R six subscales, replicating
      prior research regarding the scale's structural validity. Criterion validity
      results were mixed, with small effect sizes for regressions predicting child
      outcomes and moderate effect sizes for regressions predicting teacher-reported
      quality. Our results lend empirical support to recent critiques of the ECERS-R,
      and we discuss implications for its future use and for the development of future
      measures.

PMID- 22468568
TI  - The relations of Arab Jordanian adolescents' perceived maternal parenting to
      teacher-rated adjustment and problems: the intervening role of perceived need
      satisfaction.
AB  - Although the effects of important parenting dimensions, such as responsiveness
      and psychological control, are well documented among Western populations,
      research has only recently begun to systematically identify psychological
      processes that may account for the cross-cultural generalization of these
      effects. A first aim of this study was to examine whether perceived maternal
      responsiveness and psychological control would relate differentially to teacher
      ratings of adolescent adjustment in a vertical-collectivist society (i.e.,
      Jordan). The most important aim of this study was to examine, on the basis of
      self-determination theory, whether these associations would be accounted for by
      perceived satisfaction of the basic psychological needs for autonomy, competence,
      and relatedness. Results in a large sample of Jordanian adolescents (N = 545)
      showed that perceived maternal psychological control and responsiveness yielded,
      respectively, a positive and negative association with teacher-rated problems,
      whereas psychological control was negatively related to teacher-rated adjustment.
      Further, these 2 parenting dimensions related to adjustment and problems via
      perceived satisfaction of the basic psychological needs for autonomy and
      competence (but not relatedness). The findings are discussed in light of the
      ongoing debate between universalistic and relativistic perspectives on parenting
      and adolescent adjustment.

PMID- 22468569
TI  - Mitigation of inflammation with foods.
AB  - Constant overproduction of pro-inflammatory molecules leads to chronic
      inflammation. Unlike acute inflammation, which is essential for healing, chronic
      inflammation can delay healing and, if left unchecked, contribute to a host of
      diseases. There is growing evidence that some dietary factors can play important
      roles in maintaining health and even reversing the progression of chronic
      diseases, with anti-inflammatory effects as important underlying mechanism. Such
      findings add to the body of evidence that certain dietary components, including
      polyphenols and other types of compounds, found in various dietary factors
      including fruits, berries, vegetables, nuts, whole grains, and foods of marine
      origin, can play an important role in attenuating and mitigating chronic pro
      inflammatory processes associated with chronic diseases. 

PMID- 22468570
TI  - Solution-phase electronegativity scale: insight into the chemical behaviors of
      metal ions in solution.
AB  - By incorporating the solvent effect into the Born effective radius, we have
      proposed an electronegativity scale of metal ions in aqueous solution with the
      most common oxidation states and hydration coordination numbers in terms of the
      effective ionic electrostatic potential. It is found that the metal ions in
      aqueous solution are poorer electron acceptors compared to those in the gas
      phase. This solution-phase electronegativity scale shows its efficiency in
      predicting some important properties of metal ions in aqueous solution such as
      the aqueous acidities of the metal ions, the stability constants of metal
      complexes, and the solubility product constants of the metal hydroxides. We have
      elaborated that the standard reduction potential and the solution-phase
      electronegativity are two different quantities for describing the processes of
      metal ions in aqueous solution to soak up electrons with different final states.
      This work provides a new insight into the chemical behaviors of the metal ions in
      aqueous solution, indicating a potential application of this electronegativity
      scale to the design of solution reactions.

PMID- 22468571
TI  - Systems-centered(r) group psychotherapy: putting theory into practice.
AB  - Systems-centered therapy (SCT) is derived from a theory of living human systems
      and practiced in individual and group therapy. Excerpts from an inpatient group
      illustrate how SCT norms, particularly functional subgrouping and the hierarchy
      of defense modification, are introduced within the first few minutes of an SCT
      group. The importance of modifying roles is also discussed, as is the
      significance of system hierarchy, isomorphy, and energy as applied in the
      practice of SCT.

PMID- 22468572
TI  - Outcomes of specific interpersonal problems for binge eating disorder: comparing
      group psychodynamic interpersonal psychotherapy and group cognitive behavioral
      therapy.
AB  - We assessed whether an attachment-based treatment, Group Psychodynamic
      Interpersonal Psychotherapy (GPIP) had a greater impact compared to Group
      Cognitive Behavioral Therapy (GCBT) on Cold/Distant and Intrusive/Needy
      interpersonal problems. Ninety-five individuals with Binge Eating Disorder (BED)
      were randomized to GPIP or GCBT and assessed at pre-, post-, and six months post
      treatment. Both therapies resulted in a significant decrease in all eight
      interpersonal problem subscales except the Nonassertive subscale. GPIP resulted
      in a greater reduction in the Cold/Distant subscale compared to GCBT, but no
      differences were found for changes in the Intrusive/Needy subscale. GPIP may be
      most relevant for those with BED who have Cold/Distant interpersonal problems and
      attachment avoidance.

PMID- 22468573
TI  - The development and content of an interpersonal psychotherapy group for postnatal
      depression.
AB  - Postnatal depression (PND) usually causes distressing symptoms for sufferers and
      significant impairments in relationships. Group Interpersonal Psychotherapy (IPT
      G) provides the experienced therapist with a brief, focused, and manualized
      approach to helping women recover from the debilitating effects of PND. This
      paper describes the background and development of IPT-G for PND. The evidence for
      the effectiveness of individual and group IPT formats with this population is
      summarized. The triad of theories underpinning IPT are discussed with an emphasis
      on the important role of attachment styles during the transition to parenthood.
      Its strengths, which include its unique package of targets, tactics, and
      techniques, are highlighted. The benefits and challenges of IPT-G are also
      explored, and the results of a randomized controlled trial are summarized.
      Finally, a case study illustrates how IPT-G specifically addresses the social
      role transitions, conflicts, losses, and social isolation that mothers commonly
      experience.

PMID- 22468574
TI  - Subgroup conflicts? Try the psychodramatic "double triad method".
AB  - The present article suggests the application of a psychodramatic action method
      for tackling subgroup conflicts in which the direct dialogue between
      representatives of two opposing subgroups is prepared step by step through an
      indirect dialogue strategy within two triads, a strategy known as the Double
      Triad Method (DTM). In order to achieve integration in the group as a whole, it
      is important that all the members of both subgroups participate actively during
      the entire process. The first part of the article briefly explores the
      theoretical background, with a special emphasis on the Phenomenological
      Dialectical Personality Model (Phe-Di PModel). In the second part, the DTM
      procedure is systematically described through its five action stages, each
      accompanied with 1) a spatial representation of the consecutive actions, 2) some
      illustrative statements for each stage, and 3) a theoretical interpretation of
      the dialectically involved personality dimensions in both protagonists. The
      article concludes with a discussion and suggestions for more extensive
      applications of the DTM method, including the question of its relationships to
      Agazarian's functional subgrouping, psychodrama, and sociodrama.

PMID- 22468575
TI  - Effectiveness of group psychotherapy for adult outpatients traumatized by abuse,
      neglect, and/or pregnancy loss: a multiple-site, pre-post-follow-up, naturalistic
      study.
AB  - The New Experience for Survivors of Trauma (NEST) is a group psychotherapy
      intervention for clients traumatized by consequences of abuse, neglect, and
      pregnancy loss. This multiple site study is the first investigation of its
      effectiveness. Ninety outpatients from a naturalistic setting completed the
      Symptom Checklist and the Sense of Coherence questionnaire at baseline, end of
      treatment, and one-year follow-up. Effectiveness was tested with statistical
      significance, effect size, and clinical significance. Clients from the total
      sample as well as from the abortion subsample showed improvement at the end of
      treatment and at follow-up. Lack of a control group is balanced to some extent by
      the high ecological validity. The findings suggest that the NEST treatment may be
      beneficial for traumatized clients and call for further research.

PMID- 22468576
TI  - Group CBT for early psychosis--are there still benefits one year later?
AB  - Our team recently conducted a randomized controlled trial comparing group
      cognitive behavior therapy for psychosis (CBTp) to group social skills training
      for symptom management and a wait-list control group, for early psychosis. The
      results at post-therapy and six months provided considerable empirical support
      for the efficacy of the group CBTp. The results of the one-year follow-up are
      described here. Given the high attrition rates, mostly in the comparison and
      control conditions, imputations were not possible, so that only the results of
      those having completed more than 50% of the group CBTp are presented. Significant
      improvements at 12 months were found for social support and insight. Negative
      symptoms remained low, whereas positive symptoms went back to pre-therapy levels.
      Challenges regarding attrition with this clientele are discussed.

PMID- 22468578
TI  - Studying the how and why of therapeutic change: the increasingly prominent role
      of mediators in group psychotherapy research.

PMID- 22468582
TI  - External cephalic version does not increase the risk of intra-uterine death: a 17
      year experience and literature review.
AB  - OBJECTIVE: To assess the risk of intra-uterine death (IUD) after external
      cephalic version (ECV). METHODS: In this retrospective cohort study, 1078
      consecutive ECVs performed between January 1994 and March 2011 in an University
      teaching hospital were extracted from the computerized database to examine the
      risk of IUD after ECV. RESULTS: A total of 1078 consecutive ECVs were performed
      over the study period. The overall successful rate was 72.8%, the successful rate
      was 63.1% in nulliparous and 82.7% in multiparous, respectively (p < 0.001).
      There was no IUD identified within 24 h after the procedure and there was only
      one case of IUD (0.09%) that occurred 4 weeks after an uncomplicated ECV.
      CONCLUSIONS: ECV is a safe procedure that does not increase the risk of IUD
      within and after 24 h of enrollment irrespective of outcome of ECV. Our findings
      have important clinical implication in terms of patient counseling regarding the
      decision on term breech management.

PMID- 22468583
TI  - Destabilization of colloidal suspensions by multivalent ions and
      polyelectrolytes: from screening to overcharging.
AB  - The destabilization of charged colloidal suspensions is studied in the presence
      of polyelectrolytes and the corresponding oligomers. Two different systems are
      investigated, namely, negatively charged particles in the presence of polyamines
      and positively charged ones in the presence of polycarboxylates. Multivalent
      oligomers of low valence destabilize the particles by screening according to the
      Schulze-Hardy rule. Polyelectrolytes induce destabilization by overcharging. Both
      regimes can be observed for oligomers of intermediate valence. The stability data
      of any valence can be rather well described by the theory of Derjaguin, Landau,
      Verwey, and Overbeek (DLVO), indicating that the interactions are mainly governed
      by van der Waals and electrostatic double-layer forces.

PMID- 22468584
TI  - Therapeutic lifestyle changes (TLCs) and mental health.

PMID- 22468585
TI  - The paradox of being both needed and rejected: the existential meaning of being
      closely related to a person with bipolar disorder.
AB  - The aim of this study was to elucidate the existential meaning of being closely
      related to a person with bipolar disorder. A qualitative, descriptive, and
      explorative design with a phenomenological meaning-oriented analysis was used.
      The findings reveal a paradoxical, existential exposure of close relatives to a
      person with bipolar disorder, being both needed and rejected whilst being
      overshadowed by the specific changeable nature of bipolar disorder. Psychiatric
      health care services are recommended to consider changes in attitudes and
      structures that may facilitate close relatives' participation in the care and
      treatment of persons with bipolar disorder.

PMID- 22468586
TI  - Experiences of a person-centred health education group intervention--a
      qualitative study among people with a persistent mental illness.

PMID- 22468587
TI  - The evolution of the advanced practice role in psychiatric mental health in New
      Jersey: 1960-2010.
AB  - This historical perspective is focused on the contribution of Hildegard E. Peplau
      in laying the foundation for advanced practice nursing and the development of the
      roles of clinical nurse specialists and psychiatric nurse practitioners. An
      overview is provided of legal developments within the state that enabled Advanced
      Practice Nurses to provide mental health services. A description of a recent
      specialized state-funded initiative is outlined, focused on the development and
      contributions of psychiatric advanced practice nurses in community settings in
      New Jersey. Implications for the advanced practice nursing role in New Jersey are
      presented based on national and state initiatives.

PMID- 22468588
TI  - The physical environment of purpose-built and non-purpose-built supported housing
      for persons with psychiatric disabilities in Sweden.
AB  - The primary aim of the present study was to investigate if methods derived from
      environmental psychology can be used to study the qualities of the physical
      environment of supported housing facilities for persons with psychiatric
      disabilities. Three units of analysis were selected: the private area, the common
      indoor area, and the outdoor area. Expert assessments of 110 features of the
      physical environment in these units and semantic environmental description of the
      visual experience of them consistently showed that purpose-built supported
      housing facilities had more physical features important for high quality
      residential environments than the non-purpose-built supported housing facilities.
      The employed methods were thus seen to be able to describe and discriminate
      between qualities in the physical environment of supported housing facilities.
      Suggestions for the development of tools for the assessment of the physical
      environment in supported housing are made.

PMID- 22468589
TI  - Successful management of disruptive behavior: a descriptive study.
AB  - The purpose of this qualitative descriptive study was to describe techniques
      nurses use to successfully manage disruptive behavior (DB) of colleagues. DB is
      any inappropriate behavior, confrontation, or conflict, ranging from verbal abuse
      to physical and sexual harassment. Nine RNs who had successfully managed DB in a
      nurse colleague participated in individual interviews. All participants felt it
      was important to confront in private unless patient safety was at risk.
      Participants' described a deliberate approach that included delaying
      confrontation, approaching the colleague calmly, and acknowledging the
      colleague's point of view. Responses to the confrontation were positive.
      Participants also reported that the ability to confront DB improved their
      practice.

PMID- 22468590
TI  - Development of an observer rating scale for caregiver communication in persons
      with Alzheimer's disease.
AB  - There have been few reported studies of communication between spouses with
      Alzheimer's disease (AD) and related dementia. An observer rating scale for
      verbal and nonverbal behavior, Verbal-Nonverbal Interaction Scale for Caregivers
      (VNVIS-CG), was developed to study caregiver communication in couples affected by
      AD. Preliminary psychometric testing showed that the VNVIS-CG evidenced good
      reliability and validity. Researchers observed both common caregiver
      communication strategies and novel strategies that have not been reported in the
      literature. In future studies, researchers can examine the relationship between
      caregiver communication and indicators of mental health. Everyday conversations
      provide fertile ground for nurses to influence family relationships. Nurses can
      teach caregivers to use strategies that promote engagement and avoid those that
      discourage participation.

PMID- 22468591
TI  - Helping self-mutilating adolescents: descriptions of Finnish nurses.
AB  - This study focused on the views of Finnish nurses in regards to providing help
      for adolescents who self-mutilate. Nine nurses participated, and when the
      interviews and written descriptions were qualitatively analysed, four main
      categories of information emerged. The first category comprises the nurses' views
      on self-mutilation. The second category describes the people who are able to be
      helpers. The third category describes the content of help, which is made up of a
      variety of acts provided by non-health professionals that promote the healthy
      development of adolescents. The fourth category describes care provided by nurses
      to adolescents who self-mutilate. Guidelines for caring for self-mutilating
      adolescents are needed, including information on the phenomenon of self
      mutilation.

PMID- 22468592
TI  - We need to talk about psychological pain.
AB  - The author responds to Dr. Shattell's suggestion (Issues in Mental Health
      Nursing, 30(5), 2009) that it may be time to add psychic pain to the Joint
      Commission on Accreditation of Healthcare Organizations' pain management
      standard. Before we do so, some level of agreement is necessary on issues
      concerning terminology, measurement, and intervention. The author offers a
      definition of psychological pain as common ground for future research and
      development in clinical care.

PMID- 22468593
TI  - Seasonal affective disorders.

PMID- 22468595
TI  - A conversation with Haldor Topsoe by Manos Mavrikakis.

PMID- 22468596
TI  - Unraveling reaction pathways and specifying reaction kinetics for complex
      systems.
AB  - Many natural and industrial processes involve a complex set of competing
      reactions that include several different species. Detailed kinetic modeling of
      such systems can shed light on the important pathways involved in various
      transformations and therefore can be used to optimize the process conditions for
      the desired product composition and properties. This review focuses on
      elucidating the various components involved in modeling the kinetics of pyrolysis
      and oxidation of polymers. The elementary free radical steps that constitute the
      chain reaction mechanism of gas-phase/nonpolar liquid-phase processes are
      outlined. Specification of the rate coefficients of the various reaction
      families, which is central to the theme of kinetics, is described. Construction
      of the reaction network on the basis of the types of end groups and reactive
      moieties in a polymer chain is discussed. Modeling frameworks based on the method
      of moments and kinetic Monte Carlo are evaluated using illustrations. Finally,
      the prospects and challenges in modeling biomass conversion are addressed.

PMID- 22468597
TI  - Nature versus nurture: developing enzymes that function under extreme conditions.
AB  - Many industrial processes used to produce chemicals and pharmaceuticals would
      benefit from enzymes that function under extreme conditions. Enzymes from
      extremophilic microorganisms have evolved to function in a variety of extreme
      environments, and bioprospecting for these microorganisms has led to the
      discovery of new enzymes with high tolerance to nonnatural conditions. However,
      bioprospecting is inherently limited by the diversity of enzymes evolved by
      nature. Protein engineering has also been successful in generating extremophilic
      enzymes by both rational mutagenesis and directed evolution, but screening for
      activity under extreme conditions can be difficult. This review examines the
      emerging synergy between bioprospecting and protein engineering in developing
      extremophilic enzymes. Specific topics include unnatural industrial conditions
      relevant to biocatalysis, biophysical properties of extremophilic enzymes, and
      industrially relevant extremophilic enzymes found either in nature or through
      protein engineering.

PMID- 22468598
TI  - Design of nanomaterial synthesis by aerosol processes.
AB  - Aerosol synthesis of materials is a vibrant field of particle technology and
      chemical reaction engineering. Examples include the manufacture of carbon blacks,
      fumed SiO(2), pigmentary TiO(2), ZnO vulcanizing catalysts, filamentary Ni, and
      optical fibers, materials that impact transportation, construction,
      pharmaceuticals, energy, and communications. Parallel to this, development of
      novel, scalable aerosol processes has enabled synthesis of new functional
      nanomaterials (e.g., catalysts, biomaterials, electroceramics) and devices (e.g.,
      gas sensors). This review provides an access point for engineers to the
      multiscale design of aerosol reactors for the synthesis of nanomaterials using
      continuum, mesoscale, molecular dynamics, and quantum mechanics models spanning
      10 and 15 orders of magnitude in length and time, respectively. Key design
      features are the rapid chemistry; the high particle concentrations but low volume
      fractions; the attainment of a self-preserving particle size distribution by
      coagulation; the ratio of the characteristic times of coagulation and sintering,
      which controls the extent of particle aggregation; and the narrowing of the
      aggregate primary particle size distribution by sintering.

PMID- 22468599
TI  - Advances and new directions in crystallization control.
AB  - The academic literature on and industrial practice of control of solution
      crystallization processes have seen major advances in the past 15 years that have
      been enabled by progress in in-situ real-time sensor technologies and driven
      primarily by needs in the pharmaceutical industry for improved and more
      consistent quality of drug crystals. These advances include the accurate
      measurement of solution concentrations and crystal characteristics as well as the
      first-principles modeling and robust model-based and model-free feedback control
      of crystal size and polymorphic identity. Research opportunities are described in
      model-free controller design, new crystallizer designs with enhanced control of
      crystal size distribution, strategies for the robust control of crystal shape,
      and interconnected crystallization systems for multicomponent crystallization.

PMID- 22468600
TI  - Single-cell analysis in biotechnology, systems biology, and biocatalysis.
AB  - Single-cell analysis (SCA) has been increasingly recognized as the key technology
      for the elucidation of cellular functions, which are not accessible from bulk
      measurements on the population level. Thus far, SCA has been achieved by
      miniaturization of established engineering concepts to match the dimensions of a
      single cell. However, SCA requires procedures beyond the classical approach of
      upstream processing, fermentation, and downstream processing because the
      biological system itself defines the technical demands. This review characterizes
      currently available microfluidics and microreactors for invasive (i.e., chemical)
      and noninvasive (i.e., biological) SCA. We describe the recent SCA omics
      approaches as tools for systems biology and discuss the role of SCA in genomics,
      transcriptomics, proteomics, metabolomics, and fluxomics. Furthermore, we discuss
      applications of SCA for biocatalysis and metabolic engineering as well as its
      potential for bioprocess optimization. Finally, we define present and future
      challenges for SCA and propose strategies to overcome current limitations.

PMID- 22468601
TI  - Molecular origins of homogeneous crystal nucleation.
AB  - We review the molecular principles underlying the homogeneous nucleation of a
      crystal phase from the melt phase, as elucidated by molecular simulation methods.
      Classical nucleation theory serves as the starting point for describing the
      nature of nucleation processes, but it does not derive from molecular principles
      itself. Density functional theory and molecular simulations offer tools for
      delving into the molecular origins of nucleation. Here, we emphasize the rapid
      development of molecular simulation methodologies for studying crystal nucleation
      from the melt. These methodologies are broadly categorized as free energy
      sampling methods, dynamical or mean first-passage time methods, and composite
      approaches that take advantage of both. The crucial selection of order parameters
      to distinguish the crystal phase from the liquid phase and important features of
      the reaction coordinate are emphasized. The system size dependence of the
      nucleation free energy barrier is also examined.

PMID- 22468602
TI  - Engineering molecular circuits using synthetic biology in mammalian cells.
AB  - Synthetic biology has made significant leaps over the past decade, and it now
      enables rational and predictable reprogramming of cells to conduct complex
      physiological activities. The bases for cellular reprogramming are mainly genetic
      control components affecting gene expression. A huge variety of these modules,
      ranging from engineered fusion proteins regulating transcription to artificial
      RNA devices affecting translation, is available, and they often feature a highly
      modular scaffold. First endeavors to combine these modules have led to
      autoregulated expression systems and genetic cascades. Analogous to the rational
      engineering of electronic circuits, the existing repertoire of artificial
      regulatory elements has further enabled the ambitious reprogramming of cells to
      perform Boolean calculations or to mimic the oscillation of circadian clocks.
      Cells harboring synthetic gene circuits are not limited to cell culture, as they
      have been successfully implanted in animals to obtain tailor-made therapeutics
      that have made it possible to restore urea or glucose homeostasis as well as to
      offer an innovative approach to artificial insemination.

PMID- 22468603
TI  - Green chemistry, biofuels, and biorefinery.
AB  - In the current climate of several interrelated impending global crises, namely,
      climate change, chemicals, energy, and oil, the impact of green chemistry with
      respect to chemicals and biofuels generated from within a holistic concept of a
      biorefinery is discussed. Green chemistry provides unique opportunities for
      innovation via product substitution, new feedstock generation, catalysis in
      aqueous media, utilization of microwaves, and scope for alternative or natural
      solvents. The potential of utilizing waste as a new resource and the development
      of integrated facilities producing multiple products from biomass is discussed
      under the guise of biorefineries. Biofuels are discussed in depth, as they not
      only provide fuel (energy) but are also a source of feedstock chemicals. In the
      future, the commercial success of biofuels commensurate with consumer demand will
      depend on the availability of new green (bio)chemical technologies capable of
      converting waste biomass to fuel in a context of a biorefinery.

PMID- 22468604
TI  - Engineering aggregation-resistant antibodies.
AB  - The ability of antibodies to bind to target molecules with high affinity and
      specificity has led to their widespread use in diagnostic and therapeutic
      applications. Nevertheless, a limitation of antibodies is their propensity to
      self-associate and aggregate at high concentrations and elevated temperatures.
      The large size and multidomain architecture of full-length monoclonal antibodies
      have frustrated systematic analysis of how antibody sequence and structure
      regulate antibody solubility. In contrast, analysis of single and multidomain
      antibody fragments that retain the binding activity of mono-clonal antibodies has
      provided valuable insights into the determinants of antibody aggregation. Here we
      review advances in engineering antibody frameworks, domain interfaces, and
      antigen-binding loops to prevent aggregation of natively and nonnatively folded
      antibody fragments. We also highlight advances and unmet challenges in developing
      robust strategies for engineering large, multidomain antibodies to resist
      aggregation.

PMID- 22468605
TI  - Nanocrystals for electronics.
AB  - Semiconductor nanocrystals are promising materials for low-cost large-area
      electronic device fabrication. They can be synthesized with a wide variety of
      chemical compositions and size-tunable optical and electronic properties as well
      as dispersed in solvents for room-temperature deposition using various types of
      printing processes. This review addresses research progress in large-area
      electronic device applications using nanocrystal-based electrically active thin
      films, including thin-film transistors, light-emitting diodes, photovoltaics, and
      thermoelectrics.

PMID- 22468606
TI  - Cultural influences on Facebook photographs.
AB  - Prior research in social psychology indicates that East Asians from
      collectivistic and interdependent sociocultural systems are more sensitive to
      contextual information than Westerners, whereas Westerners with individualistic
      and independent representation have a tendency to process focal and discrete
      attributes of the environment. Here we have demonstrated that such systematic
      cultural variations can also be observed in cyberspace, focusing on self
      presentation of photographs on Facebook, the most popular worldwide online social
      network site. We examined cultural differences in face/frame ratios for Facebook
      profile photographs in two studies. For Study 1, 200 digital profile face
      photographs of active Facebook users were randomly selected from native and
      immigrant Taiwanese and Americans. For Study 2, 312 Facebook profiles of
      undergraduate students of six public universities in East Asia (Hong Kong,
      Singapore, and Taiwan) and the United States (California and Texas) were randomly
      selected. Overall, the two studies clearly showed that East Asian Facebook users
      are more likely to deemphasize their faces compared to Americans. Specifically,
      East Asians living in Hong Kong, Singapore, and Taiwan exhibited a predilection
      for context inclusiveness in their profile photographs, whereas Americans tended
      to prioritize their focal face at the expense of the background. Moreover, East
      Asian Facebook users had lower intensity of facial expression than Americans on
      their photographs. These results demonstrate marked cultural differences in
      context-inclusive styles versus object-focused styles between East Asian and
      American Facebook users. Our findings extend previous findings from the real
      world to cyberspace, and provide a novel approach to investigate cognition and
      behaviors across cultures by using Facebook as a data collection platform.

PMID- 22468607
TI  - On the measurement of criterion noise in signal detection theory: the case of
      recognition memory.
AB  - Traditional approaches within the framework of signal detection theory (SDT;
      Green & Swets, 1966), especially in the field of recognition memory, assume that
      the positioning of response criteria is not a noisy process. Recent work
      (Benjamin, Diaz, & Wee, 2009; Mueller & Weidemann, 2008) has challenged this
      assumption, arguing not only for the existence of criterion noise but also for
      its large magnitude and substantive contribution to individuals' performance. A
      review of these recent approaches for the measurement of criterion noise in SDT
      identifies several shortcomings and confoundings. A reanalysis of Benjamin et
      al.'s (2009) data sets as well as the results from a new experimental method
      indicate that the different forms of criterion noise proposed in the recognition
      memory literature are of very low magnitudes, and they do not provide a
      significant improvement over the account already given by traditional SDT without
      criterion noise.

PMID- 22468608
TI  - Constrained source-based morphometry identifies structural networks associated
      with default mode network.
AB  - We present constrained source-based morphometry (SBM), a multivariate semiblind
      data-driven approach, to explore a possible brain-wide structural network in both
      gray matter (GM) and white matter (WM) associated with the functional default
      mode network (DMN). With this approach, we utilize seed regions associated with
      the DMN as constraints on GM maps and derive a joint GM and WM structural network
      automatically through a multivariate data-driven approach. In this article, we
      first provide a simulation to validate the constrained SBM approach. The approach
      was then applied to structural magnetic resonance imaging and diffusion tensor
      imaging data obtained from 102 healthy controls. Regions that have consistently
      reported to be associated with the DMN were used to create an a priori mask that
      was integrated within an independent component analysis framework to derive the
      structural network associated with the DMN. We identified a set of GM and
      corresponding WM regions contributing to a structural network underlying the
      functional DMN. The GM regions consisted mainly of the precuneus, superior and
      medial frontal gyri, middle temporal gyrus, hippocampus, cuneus, and cerebellum.
      The WM regions included the cingulum, corpus callosum, corona radiata,
      association fibers, and middle cerebellar peduncle. Significant gender
      differences in the relationship between intelligence quotient (IQ) and the
      identified structural network were observed. Our findings suggest that the
      functional DMN is underpinned by a corresponding brain-wide structural network.
      The constrained SBM approach is additionally applicable to a wide variety of
      problems identifying structural networks from seed regions.

PMID- 22468609
TI  - Bright and efficient full-color colloidal quantum dot light-emitting diodes using
      an inverted device structure.
AB  - We report highly bright and efficient inverted structure quantum dot (QD) based
      light-emitting diodes (QLEDs) by using solution-processed ZnO nanoparticles as
      the electron injection/transport layer and by optimizing energy levels with the
      organic hole transport layer. We have successfully demonstrated highly bright
      red, green, and blue QLEDs showing maximum luminances up to 23,040, 218,800, and
      2250 cd/m(2), and external quantum efficiencies of 7.3, 5.8, and 1.7%,
      respectively. It is also noticeable that they showed turn-on voltages as low as
      the bandgap energy of each QD and long operational lifetime, mainly attributed to
      the direct exciton recombination within QDs through the inverted device
      structure. These results signify a remarkable progress in QLEDs and offer a
      practicable platform for the realization of QD-based full-color displays and
      lightings.

PMID- 22468610
TI  - Comparative parasitism of the fish Plagioscion squamosissimus in native and
      invaded river basins.
AB  - Biological invasions are considered a major threat to biodiversity around the
      world, but the role of parasites in this process is still little investigated.
      Here, we compared parasite infections of a host species in the areas where it
      originated and where it was introduced, and in native and introduced species in
      the same environment, using the endoparasites of the fish Plagioscion
      squamosissimus (Sciaenidae) in 3 Brazilian basins. Samples were taken in 2 rivers
      where the species is native, i.e., Solimoes River (SO) and Tocantins River (TO),
      and where the species was introduced, the upper Parana River (PR). In addition,
      abundances of diplostomids and larval nematodes were compared between P.
      squamosissimus and 2 native competitors in the PR, Hoplias malabaricus and
      Raphiodon vulpinus. In total, 13 species of endoparasites were recorded, but only
      Austrodiplostomum sp. and cestode cysts were present in all localities. Although
      infracommunity richness was similar, their species composition was slightly
      different among localities. General linear models using the relative condition
      factor of fish as response variables, and abundance of the most prevalent
      parasites as possible predictors showed that the condition of fish is negatively
      correlated with parasite abundance only in the native range (TO). Abundance of
      diplostomid eye flukes was higher in the PR, and in the native species H.
      malabaricus when compared to the invader, which might present an advantage for P.
      squamosissimus if they compete for prey. However, although P. squamosissimus may
      have lost some of its native parasites during its introduction to the PR, it is
      now possibly acting as a host for native generalist parasites.

PMID- 22468612
TI  - Preparation of cationic biodegradable dextran microspheres loaded with BSA and
      study on the mechanism of protein loading.
AB  - AIM: The aim of this study was to investigate the feasibility of cationic
      biodegradable dextran microspheres loaded with bovine serum albumin (BSA)
      posterior to gel formation (postloading). METHOD: Positively charged microspheres
      were prepared by polymerization of hydroxylethyl methacrylate-derivatized dextran
      (dex-HEMA) and dimethyl aminoethyl methacrylate (DMAEMA) in an aqueous two-phase
      system and net positive surface charge increased with increasing amounts of
      DMAEMA. Loading efficiency of dextran microspheres for BSA was analyzed through
      fluorescence microscopy and measured. The BSA release from the cationic dextran
      microspheres in vitro was investigated. RESULTS: BSA could penetrate into
      cationic dextran microspheres, but neutral dextran microspheres could not.
      Protein-loading efficiency (98.1--100%) by postloading was higher compared with
      by preloading (60.2--75.9%), when the incubated protein concentration was below
      1.5 mg/ml. Even though BSA is incorporated in the hydrogel network based on
      electrostatic interaction, a controlled release can be achieved by varying the
      initial network density of the microspheres. CONCLUSION: These findings suggest
      that it is a feasible method to prepare dextran microspheres with high surface
      charge density to efficiently adsorb oppositely charged protein based on
      electrostatic interactions.

PMID- 22468611
TI  - Cellular quantitative structure-activity relationship (Cell-QSAR): conceptual
      dissection of receptor binding and intracellular disposition in antifilarial
      activities of Selwood antimycins.
AB  - We present the cellular quantitative structure-activity relationship (cell-QSAR)
      concept that adapts ligand-based and receptor-based 3D-QSAR methods for use with
      cell-level activities. The unknown intracellular drug disposition is accounted
      for by the disposition function (DF), a model-based, nonlinear function of a
      drug's lipophilicity, acidity, and other properties. We conceptually combined the
      DF with our multispecies, multimode version of the frequently used ligand-based
      comparative molecular field analysis (CoMFA) method, forming a single correlation
      function for fitting the cell-level activities. The resulting cell-QSAR model was
      applied to the Selwood data on filaricidal activities of antimycin analogues.
      Their molecules are flexible, ionize under physiologic conditions, form different
      intramolecular H-bonds for neutral and ionized species, and cross several
      membranes to reach unknown receptors. The calibrated cell-QSAR model is
      significantly more predictive than other models lacking the disposition part and
      provides valuable structure optimization clues by factorizing the cell-level
      activity of each compound into the contributions of the receptor binding and
      disposition.

PMID- 22468613
TI  - Drug safety evaluation profile of  stavudine plus lamivudine  for HIV-1/AIDS
      infection.
AB  - INTRODUCTION: The lamivudine (3TC) + stavudine (d4T) combination is still widely
      used as part of first-line therapy for HIV-1-infected patients in low-resource
      countries. This review is intended to assess the benefits and risks in terms of
      safety of d4T + 3TC-based combination antiretroviral therapy (ART) for the
      treatment of HIV-1 infection. AREAS COVERED: The most relevant papers related to
      the safety of d4T + 3TC-based ART were selected and summarized. EXPERT OPINION:
      In industrialized countries, the 3TC + d4T combination is not recommended for
      initial therapy because of long-term metabolic toxicities associated with d4T. In
      developing countries, it may have a role in the treatment of HIV-infected
      patients if there is no other chance for starting antiretroviral therapy.

PMID- 22468614
TI  - Change in self-stigma among persons with schizophrenia enrolled in
      rehabilitation: associations with self-esteem and positive and emotional
      discomfort symptoms.
AB  - Self-stigma is a barrier to the recovery of persons with schizophrenia. Little is
      known about whether participation in rehabilitation is naturalistically linked to
      declines in self-stigma, and if so, what is correlated with changes in self
      stigma. The current study examined in a quasi-experimental design the rate of
      change of self-stigma and whether changes were correlated with self-esteem,
      positive symptoms, and emotional distress for persons enrolled in rehabilitation.
      Symptoms were measured using the Positive and Negative Syndrome Scale (Kay,
      Fizsbein, & Opler, 1987), self-esteem was measured with the Multidimensional Self
      Esteem Inventory (Lysaker, Ringer, & Davis, 2008), and self-stigma was assessed
      using the Internalized Stigma of Mental Illness Scale (Ritsher, Otilingam, &
      Grajales, 2003). Seventy persons with schizophrenia who worked at least one month
      in a vocational rehabilitation program were assessed on all measures at baseline
      and five months later. Results indicated a 25% decrease in self-stigma for 38% of
      the sample; these individuals tended to have less emotional distress both at
      baseline and follow-up, and had higher levels of self-esteem at follow-up. No
      differences in positive symptoms were found for groups whose stigma did or did
      not decrease. Results suggest that decreases in self-stigma may be correlated
      with increased self-esteem, while higher levels of emotional distress may be a
      barrier to stigma reduction.

PMID- 22468615
TI  - Promoting spontaneous adverse drug reaction reporting in hospitals using a
      hyperlink to the online reporting form: an ecological study in Portugal.
AB  - BACKGROUND: Spontaneous adverse drug reaction (ADR) reporting has been described
      as an efficient method to detect drug safety signals. However, under-reporting is
      a major issue undermining the effectiveness of spontaneous reports. Among
      hospitalized patients, ADRs are a particularly serious problem because these
      patients are often treated with more than one drug, and these drugs are often new
      and aggressive. OBJECTIVE: To promote spontaneous ADR reporting by healthcare
      professionals working in hospitals in the northern regions of Portugal, we
      propose the inclusion of a hyperlink to an online ADR reporting form on
      hospitals' electronic patient records (EPRs). The main aim of this study was to
      evaluate the impact of these hyperlinks on the number of spontaneous ADR reports
      to the Northern Pharmacovigilance Centre (UFN - Unidade de Farmacovigilancia do
      Norte). We also assess the number of daily UFN website visits before and after
      the inclusion of the hyperlinks. METHODS: An ecological study was performed in
      northern Portuguese hospitals from 2006 to 2010. The hyperlinks were included in
      either EPRs or on computer desktops. The median of spontaneous ADR reports (total
      and online) per month and the respective ranges were presented before and after
      the intervention in all hospitals in this study. The comparisons were performed
      using the Mann-Whitney U-test. RESULTS: Sixteen hospital centres were involved in
      the study (27 hospitals). Eleven centres (18 hospitals) included the hyperlinks.
      Considering the hospitals with hyperlink access to the EPRs, the median ADR
      reports per month significantly increased, from two (range 0-12) to five reports
      (range 1-17). The median of ADR reports per month using the online form also
      increased significantly, from one (range 0-5) before the intervention to four
      (range 1-17) after it. Moreover, serious ADRs increased 3-fold, and non
      previously described ADRs increased 4.5-fold. None of these significant increases
      were observed in the hospitals where the hyperlink was not installed. We also
      found a significant increase in daily UFN website visits, from ten before the
      intervention to 27 after it (p < 0.001). CONCLUSION: The increase in ADR
      reporting shows that the inclusion of hyperlinks to online ADR reporting forms is
      an easy and cost-effective way to change health professional behaviours with
      regard to spontaneous ADR reports.

PMID- 22468616
TI  - Standing in the glory or shadow of the past self: cultures differ in how much the
      past self affects current subjective well-being.
AB  - Research in the past 2 decades has made great strides in understanding cross
      cultural differences in the correlates and causes of subjective well-being. On
      the basis of past findings on the cross-cultural differences in temporal
      perspectives of the self, the present research examined a cross-cultural
      difference in individuals' subjective well-being as a function of how positively
      they viewed their present and past selves. Study 1 showed that both European and
      Asian Americans had higher subjective well-being when they viewed their present
      selves more positively. However, positive evaluations of the past self were
      accompanied by higher subjective well-being only among Asian Americans. Study 2
      showed that when induced to think positively (vs. negatively) of the present
      self, both European and Asian Americans judged their current lives more
      favorably. However, when led to view the past self positively (vs. negatively),
      only Asian Americans made more favorable judgments about their current lives.

PMID- 22468617
TI  - Overlapping neural substrates between intentional and incidental down-regulation
      of negative emotions.
AB  - Emotion regulation can be achieved in various ways, but few studies have
      evaluated the extent to which the neurocognitive substrates of these distinct
      operations overlap. In the study reported here, functional magnetic resonance
      imaging (fMRI) was used to measure activity in the amygdala and prefrontal cortex
      of 10 participants who completed two independent tasks of emotion regulation
      reappraisal, measuring intentional emotion regulation, and affect labeling,
      measuring incidental emotion regulation-with the objective of identifying
      potential overlap in the neural substrates underlying each task. Analyses focused
      on a priori regions of interest in the amygdala and inferior frontal gyrus (IFG).
      For both tasks, fMRI showed decreased amygdala activation during emotion
      regulation compared with emotion conditions. During reappraisal, this decrease in
      amygdala activation was accompanied by a proportional decrease in emotional
      intensity ratings; during affect labeling, the decrease in amygdala activation
      correlated with self-reported aggression. Importantly, across participants, the
      magnitude of decrease in amygdala activation during reappraisal correlated with
      the magnitude of decrease during affect labeling, even though the tasks were
      administered on separate days, and values indexing amygdala activation during
      each task were extracted independently of one another. In addition, IFG-amygdala
      connectivity, assessed via psychophysiological interaction analysis, overlapped
      between tasks in two regions within the right IFG. The results suggest that the
      two tasks recruit overlapping regions of prefrontal cortex, resulting in similar
      reductions in amygdala activation, regardless of the strategy employed.
      Intentional and incidental forms of emotion regulation, despite their
      phenomenological differences, may therefore converge on a common neurocognitive
      pathway.

PMID- 22468618
TI  - Attachment anxiety and attentional control predict immediate and delayed
      emotional Stroop interference.
AB  - Attachment anxiety has been associated with a hyperactivating response to threat.
      A modified emotional Stroop task was used to investigate temporal characteristics
      of the threat response by assessing response latencies to interpersonally
      threatening words (immediate interference) and two directly subsequent neutral
      filler words (delayed interference). Greater immediate and delayed interference
      to threatening words was observed (n = 125), with higher levels of attachment
      anxiety associated with immediate interference to threatening cues, and lower
      levels with delayed interference. Thus, attachment anxiety was related to the
      speed at which moderate perceived threat disrupted ongoing processes under top
      down attentional control. Furthermore, top-down attentional control moderated the
      extent to which immediate or delayed interference was observed. Among
      participants who demonstrated relatively stronger top-down attentional control,
      immediate and delayed interference to threatening cues was minimal, suggesting
      that results involving emotional Stroop interference were primarily attributable
      to participants with relatively weaker top-down attentional control. The
      implications of these findings are considered within the broader context of
      performance-based and neuroimaging research, with suggestions for future applied
      research.

PMID- 22468619
TI  - Threat-relevance impairs executive functions: negative impact on working memory
      and response inhibition.
AB  - The effects of emotional stimulus content on attention are well-known. In
      contrast, the impact of emotional information on higher executive control
      functions is undetermined. To elucidate the role of negative emotion in cognitive
      control, 56 adult female participants performed a combined working memory and
      response inhibition task, with threat-relevant (spider and snake) and neutral
      (flower and mushroom) stimuli. Threat-relevant stimuli impaired performance, by
      causing prolonged response times to working memory items and increased response
      inhibition error rate relative to neutral stimuli. The impaired response
      inhibition was only evident when threat-relevant stimuli co-occurred with working
      memory matches, in line with a common resource pool view of executive functions
      and emotion processing. Individual differences in reported fear of spiders were
      associated with differences of inhibitory control, while fear of snakes was
      associated with impaired overall accuracy on working memory trials. The results
      are discussed in relation to the dual-competition framework for interaction
      between executive functions and emotion (Pessoa, 2009).

PMID- 22468620
TI  - Less is more: the effects of very brief versus clearly visible exposure.
AB  - This study compared the effects of exposure to masked and unmasked phobic stimuli
      on phobic behavior. Participants were identified as spider-phobic with a
      questionnaire and a Behavioral Avoidance Test (BAT) with a live tarantula (N =
      101). One week later, they were administered one of three types of exposure: very
      brief (25 ms) or clearly visible (120 ms) images of spiders, or very brief images
      of flowers. They reported ratings of subjective distress just before and after
      these exposures, and engaged in the BAT again thereafter. Two weeks later, 57
      participants returned for a follow-up BAT. The results indicated a double
      dissociation between the effects of very brief and clearly visible exposure: the
      former reduced avoidance of the tarantula and did not affect distress, whereas
      the latter increased distress but did not affect avoidance. The behavioral effect
      lasted for two weeks. These findings suggest that avoidance of a feared object
      can be reduced without full conscious awareness. The theoretical implications are
      discussed.

PMID- 22468621
TI  - Platinum(II) diimine complexes with halide/pseudohalide ligands and dangling
      trialkylamine or ammonium groups.
AB  - A series of platinum(II) complexes with the formulas
      Pt(diimine)(pip(2)NCNH(2))(L)(2+) [pip(2)NCNH(2)(+) = 2,6
      bis(piperidiniummethyl)phenyl cation; L = Cl, Br, I, NCS, OCN, and NO(2); diimine
      = 1,10-phenanthroline (phen), 5-nitro-1,10-phenanthroline (NO(2)phen), and 5,5'
      ditrifluoromethyl-2,2'-bipyridine (dtfmbpy)] were prepared by the treatment of
      Pt(pip(2)NCN)Cl with a silver(I) salt followed by the addition of the diimine and
      halide/pseudohalide under acidic conditions. Crystallographic data as well as
      (1)H NMR spectra establish that the metal center is bonded to a bidentate
      phenanthroline and a monodentate halide/pseudohalide. The pip(2)NCNH(2)(+) ligand
      with protonated piperidyl groups is monodentate and bonded to the platinum
      through the phenyl ring. Structural and spectroscopic data indicate that the
      halide/pseudohalide group (L(-)) and the metal center in
      Pt(phen)(pip(2)NCNH(2))(L)(2+) behave as Bronsted bases, forming intramolecular
      NH...L/NH...Pt interactions involving the piperidinium groups. A close
      examination of the 10 structures reported here reveals linear correlations
      between N-H...Pt/L angles and H...Pt/L distances. In most cases, the N-H bond is
      directed toward the Pt-L bond, thereby giving the appearance that the proton
      bridges the Pt and L groups. In contrast to observations for
      Pt(tpy)(pip(2)NCN)(+) (tpy = 2,2';6',2"-terpyridine), the electrochemical
      oxidation of deprotonated adducts, Pt(diimine)(L)(pip(2)NCN), is chemically and
      electrochemically irreversible.

PMID- 22468622
TI  - Crucial role of protein flexibility in formation of a stable reaction transition
      state in an alpha-amylase catalysis.
AB  - Conformational flexibility of proteins provides enzymes with high catalytic
      activity. Although the conformational flexibility is known to be pivotal for the
      ligand binding and release, its role in the chemical reaction process of the
      reactive substrate remains unclear. We determined a transition state of an
      enzymatic reaction in a psychrophilic alpha-amylase by a hybrid molecular
      simulation that allows one to identify the optimal chemical state in an extensive
      conformational ensemble of protein. The molecular simulation uncovered that
      formation of the reaction transition state accompanies a large and slow movement
      of a loop adjacent to the catalytic site. Free energy calculations revealed that,
      although catalytic electrostatic potentials on the reactive moiety are formed by
      local and fast reorganization around the catalytic site, reorganization of the
      large and slow movement of the loop significantly contributes to reduction of the
      free energy barrier by stabilizing the local reorganization.

PMID- 22468624
TI  - Structural annotation and elucidation of conjugated phenolic compounds in black,
      green, and white tea extracts.
AB  - Advanced analytical approaches consisting of both LC-LTQ-Orbitrap Fourier
      transformed (FT)-MS and LC-time-of-flight-(TOF)-MS coupled to solid-phase
      extraction (SPE) NMR were used to obtain more insight into the complex phenolic
      composition of tea. On the basis of the combined structural information from (i)
      accurate mass fragmentation spectra, derived by using LC-Orbitrap FTMS(n), and
      (ii) proton NMR spectra, derived after LC-TOFMS triggered SPE trapping of
      selected compounds, 177 phenolic compounds were annotated. Most of these
      phenolics were glycosylated and acetylated derivatives of flavan-3-ols and
      flavonols. Principal component analysis based on the relative abundance of the
      annotated phenolic compounds in 17 commercially available black, green, and white
      tea products separated the black teas from the green and white teas, with
      epicatechin-3,5-di-O-gallate and prodelphinidin-O-gallate being among the main
      discriminators. The results indicate that the combined use of LC-LTQ-Orbitrap
      FTMS and LC-TOFMS-SPE-NMR leads to a more comprehensive metabolite description
      and comparison of tea and other plant samples.

PMID- 22468623
TI  - Daily intake of heat-killed Lactobacillus plantarum L-137 enhances type I
      interferon production in healthy humans and pigs.
AB  - We have previously reported that oral administration of heat-killed Lactobacillus
      plantarum L-137 (HK L-137) stimulates innate immunity for production of type I
      interferon (IFN) which subsequently augments host defense against influenza A
      virus infection in mice. We here examined the effect of HK L-137 intake on type I
      IFN in humans. Sixteen subjects were randomly assigned to receive a tablet
      containing 10 mg of HK L-137 or a matching tablet for 8 weeks and the serum
      levels of type I IFN were examined before and after the first or second dose of
      the trivalent inactivated influenza vaccine. There were no differences in the
      seroresponse rate, the seroprotection rate and the geometric mean Ab titers after
      either the first or second dose of vaccine between the HK L-137 group and the
      control group. On the other hand, the levels of IFN-beta were significantly
      higher in the HK L-137 group than in the control group before vaccination
      although the vaccination conferred little additional induction of IFN-beta. We
      further examined IFN-beta gene expression in the whole blood cells of pigs fed on
      a diet containing HK L-137 and found that the IFN-beta mRNA levels were
      significantly higher in the HK L-137 group than in the control group. The finding
      that daily intake of HK L-137 enhances type I IFN production and host defense
      against influenza A virus infection in mice may be applied to at least two
      additional species.

PMID- 22468625
TI  - Age differences in contingency judgement linked to perceptual segregation.
AB  - We demonstrate large differences in judging positive and null contingencies
      between younger and older adults with a task commonly used to explore cue
      competition in both contingency and causality judgements. The one-phase blocking
      task uses two cues, with separate contingencies with the same outcome. The age
      differences persisted even when participants knew in advance which of the two
      contingencies to judge. The age differences disappeared, however, when the
      stimulus display contained markers aiding perceptual segregation. We suggest that
      the age differences elicited in the one-phase blocking task are linked to
      decrements in perceptual segregation.

PMID- 22468626
TI  - Local mapping of generation and recombination lifetime in BiFeO3 single crystals
      by scanning probe photoinduced transient spectroscopy.
AB  - Carrier lifetime in photoelectric processes is the average time an excited
      carrier is free before recombining or trapping. Lifetime is directly related to
      defects and it is a key parameter in analyzing photovoltaic effects in
      semiconductors. We show here a scanning probe method combined with photoinduced
      current spectroscopy that allows mapping with nanoscale resolution of the
      generation and recombination lifetimes. Using this method we have analyzed the
      mechanism of the abnormal photovoltaic effect in multiferroic bismuth ferrite,
      BiFeO(3). We found that generation and recombination lifetimes in BiFeO(3) are
      large due to complex generation and recombination processes that involve shallow
      energy levels in the band gap. The domain walls do not play a major role in the
      photovoltaic mechanism.

PMID- 22468627
TI  - Single-dose pharmacokinetics of different oral sodium nitrite formulations in
      diabetes patients.
AB  - BACKGROUND: Diabetic foot ulcers, although associated with macrovascular disease
      and neuropathy, have a microvascular disease causing ischemia not amenable to
      surgical intervention. Nitrite selectively releases nitric oxide in ischemic
      tissues, and diabetes subjects have low nitrite levels that do not increase with
      exercise. This study explores the safety and pharmacokinetics of a single dose of
      sodium nitrite in subjects with diabetic foot ulcers. SUBJECTS AND METHODS: Using
      a blinded, randomized crossover study design, 12 subjects with diabetes mellitus
      and active or healed foot ulcers received a single dose of sodium nitrite on two
      occasions 7-28 days apart, once with an immediate release (IR) formulation and
      once with an enteric-coated (EC) formulation for delayed release. Serum nitrite,
      nitrate, methemoglobin, sulfhemoglobin, blood pressure, pulse rate, complete
      blood count, chemistry panel, electrocardiogram, and adverse events were followed
      for up to 6 h after each dose. The IR and EC nitrite levels were analyzed by one
      way analysis of variance and by pharmacokinetic modeling. RESULTS: The IR
      formulation elevated nitrite levels between 0.25 and 0.75 h (P<0.05). The EC
      formulation did not elevate nitrite levels significantly, but both formulations
      gave plasma nitrite levels previously suggested to be therapeutic (approximately
      2-5 MUM). The IR formulation gave an asymptomatic blood pressure drop of 10/6 mm
      Hg (P<0.003), and two subjects experienced mild flushing. There was no elevation
      of methemoglobin or other safety concerns. Pharmacokinetic modeling of plama
      nitrite levels gave r(2) values of 0.81 and 0.97 for the fits for IR and EC
      formulations, respectively. CONCLUSIONS: Oral sodium nitrite administration is
      well tolerated in diabetes patients.

PMID- 22468628
TI  - Pseudopolarography of copper complexes in seawater using a vibrating gold
      microwire electrode.
AB  - Copper (Cu) in seawater can be determined by anodic stripping voltammetry using a
      vibrating gold microwire electrode (VGME) with a much lower limit of detection
      than using a mercury electrode, enabling detection of labile Cu at trace level.
      The possibility of pseudopolarography of Cu using the VGME is investigated here
      and is calibrated against known chelating agents. The sensitivity much (15-fold)
      improved by application of a desorption step to remove adsorbed organic
      substances and excess anions. The notorious tendency of solid electrodes to be
      affected by memory effects was overcome by a conditioning interval between
      measurements that stabilized the electrode response. Model ligands, including
      EDTA, humic substances (HS), and glutathione (examples of natural ligands) were
      analyzed to calibrate the half-wave shift to complex stability. The half-wave
      shift on the VGME is much greater (~2*) than that on the mercury drop electrode
      which is attributed to several parameters including a much (5-fold) thinner
      diffusion layer on the VGME. Experiments showed that the same procedure is
      suitable for pseudopolarography of zinc. Application of the new method to samples
      from the Irish Sea showed Cu occurring in several complexes, all strongly bound,
      and some occurring in the electrochemically reversible region of the
      pseudopolarogram. The humic substance complex of Cu was also found to occur in
      the reversible region of the pseudopolarogram. The pseudopolarograms of Cu in
      seawater were unaffected by sample filtration and did not require purging to
      remove dissolved oxygen, suggesting that this method can be readily used as part
      of an in situ measuring system.

PMID- 22468629
TI  - Tyrosinase inhibitor-loaded microsponge drug delivery system: new approach for
      hyperpigmentation disorders.
AB  - OBJECTIVE: The aim of the present investigation was to design and formulate
      appropriate form of glabridin, using microsponge drug delivery system. METHOD:
      Microsponges were prepared by emulsion solvent evaporation method and
      characterized by drug loading, infrared spectroscopy and scanning electron
      microscopy. In vitro diffusion studies of gel formulation were performed using
      ethanol: phosphate buffer (1:1) mixture as receptor medium. Animal studies were
      carried out using brownish guinea pigs with UV-induced pigmentation model.
      RESULTS: Prepared microsponges were predominantly yellowish, free-flowing and
      spherical in shape. The infrared spectra revealed the absence of drug polymer
      interaction. Scanning electron microscopy (SEM) and porosity studies confirmed
      spherical and porous nature. In vitro release studies data depicted highest
      correlation with Higuchi treatment. Animal studies also supported the better
      depigmenting activity as compared to plain gel. CONCLUSION: Glabridin microsponge
      loaded gel could be efficacious in treating various hyperpigmentation disorders.

PMID- 22468630
TI  - Prolonged retention and in vivo evaluation of cationic nanoparticles loaded with
      Mitomycin C designed for intravesical chemotherapy of bladder tumours.
AB  - To overcome the recurrence problem in bladder tumours; nanoparticles with
      positive surface charge may improve interaction with biological membranes for
      intravesical administration. The aim of this study was to design, develop and
      evaluate (in vitro-in vivo) cationic nanoparticles based on chitosan, poly-L
      lysine or polycaprolactone for the effective intravesical delivery of
      chemotherapeutic agent MMC in a rat model. Poly-L-lysine-coated polycaprolactone
      nanoparticles and chitosan-coated polycaprolactone nanoparticles were prepared by
      the double emulsion technique. Chitosan nanoparticles were prepared by ionic
      gelation. It was found that nanoparticle formulations of 160-320 nm in size can
      be produced in 14-35% encapsulation efficiency. Variability in the particle size
      of nanoparticles depended on the preparation method. Encapsulation was increased
      by two-fold for CS-PCL as a result of the double emulsion technique. Commercial
      MMC product in solution form and cationic nanoparticle formulations were compared
      for in vivo bladder retention properties and effect of formulations on urine
      volume.

PMID- 22468631
TI  - Optical properties of substituted piperidine containing natural quinolizidine
      alkaloids - theoretical versus experimental study.

PMID- 22468632
TI  - "Krokodil":revival of an old drug with new problems.
AB  - In order to summarize current knowledge about the drug "Krokodil" a systematic
      review including a literature search of the databases PubMed, Embase, Scopus, and
      Google was conducted in December 2011. According to information acquired,
      "Krokodil" is a mixture of several substances and was first reported to have been
      used in Russia in 2003. The core agent of "Krokodil" is desomorphine, an opioid
      analogue that can be easily and cheaply manufactured by oneself. Self-production
      results in a contaminated suspension that is injected intravenously. Due to its
      pharmacologic features, desomorphine shows a high potential to cause dependence.
      Against the background of first possible cases of "Krokodil" use in Western
      Europe, it appears advisable to provide information regarding the fatal
      consequences of "Krokodil."

PMID- 22468633
TI  - Conditioned [corrected] stimulus informativeness governs conditioned stimulus
      unconditioned stimulus associability.
AB  - In a conditioning protocol, the onset of the conditioned stimulus ([CS]) provides
      information about when to expect reinforcement (unconditioned stimulus [US]).
      There are two sources of information from the CS in a delay conditioning paradigm
      in which the CS-US interval is fixed. The first depends on the informativeness,
      the degree to which CS onset reduces the average expected time to onset of the
      next US. The second depends only on how precisely a subject can represent a fixed
      duration interval (the temporal Weber fraction). In three experiments with mice,
      we tested the differential impact of these two sources of information on rate of
      acquisition of conditioned responding (CS-US associability). In Experiment 1, we
      showed that associability (the inverse of trials to acquisition) increased in
      proportion to informativeness. In Experiment 2, we showed that fixing the
      duration of the US-US interval or the CS-US interval or both had no effect on
      associability. In Experiment 3, we equated the increase in information produced
      by varying the C/T ratio with the increase produced by fixing the duration of the
      CS-US interval. Associability increased with increased informativeness, but, as
      in Experiment 2, fixing the CS-US duration had no effect on associability. These
      results are consistent with the view that CS-US associability depends on the
      increased rate of reward signaled by CS onset. The results also provide further
      evidence that conditioned responding is temporally controlled when it emerges.

PMID- 22468634
TI  - Structure of the O-antigen polysaccharide present in the lipopolysaccharide of 
      Cronobacter dublinensis  (subspecies lactaridi or lausannensis) HPB 3169.
AB  - Cronobacter dublinensis (formerly Enterobacter sakazakii) HPB 3169 is a
      pathogenic Gram-negative bacterium that produces a smooth-type lipopolysaccharide
      in which the antigenic O-polysaccharide component was determined to be a
      repeating pentasaccharide unit composed of L-rhamnose; 2-acetamido-2-deoxy-D
      glucose; 3,6-dideoxy-3-(R)-3-hydroxybutyramido-D-glucose; and 3-deoxy-manno-oct-2
      ulosonic acid in the respective molar ratio 2:1:1:1. Chemical and 2D NMR analyses
      of the O-polysaccharide and a pentasaccharide derived by the mild acid hydrolysis
      of the ketosyl linkage of the Kdo (3-deoxy-D-manno-2-octulosonic acid) residue in
      the O-polysaccharide established that the O-antigen is a high molecular mass
      unbranched polymer of a repeating pentasaccharide unit and has the structure [see
      formula in text] where Bu is a (R)-3-hydroxybutanoyl substituent. The O-antigen
      is structurally similar to that of the recently reported Cronobacter sakazakii
      strain G706 (designated as serotype O5), except that in strain G706 the d-Qui3N
      is in its N-acetyl form, in contrast to its presence as a 3-deoxy-3-(R)-3
      hydroxybutyramido derivative in the C. sakazakii HPB 3169 strain O-antigen.

PMID- 22468635
TI  - Drug safety evaluation of  pregabalin.
AB  - INTRODUCTION: Pregabalin is an anticonvulsant with one known mechanism of action
      which is used most specifically in the management of neuropathic pain. AREAS
      COVERED: The adverse effect profile of this medication from controlled,
      randomized studies as well as open and long-term studies is described with
      consideration of the evidence-based results for pregabalin's clinical use. EXPERT
      OPINION: Pregabalin is a mostly well tolerated medication for the management of
      neuropathic pain and other conditions. Pregabalin use is associated with benign
      central nervous system and systemic adverse effects with very limited metabolic,
      idiosyncratic, or teratogenic adverse effects. Understanding of these adverse
      effects is essential for the clinician treating the patient and for the patient
      receiving treatment. Sedation, dizziness, peripheral edema, and dry mouth are the
      most prevalent adverse events experienced in all clinical populations. Other
      adverse effects are rare, but are discussed.

PMID- 22468636
TI  - Structure, orientation, and surface interaction of Alzheimer amyloid-beta
      peptides on the graphite.
AB  - The misfolding and aggregation of amyloid-beta (Abeta) peptides into amyloid
      fibrils in solution and on the cell membrane has been linked to the pathogenesis
      of Alzheimer's disease. Although it is well-known that the presence of different
      surfaces can accelerate the aggregation of Abeta peptides into fibrils, surface
      induced conformation, orientation, aggregation, and adsorption of Abeta peptides
      have not been well understood at the atomic level. Here, we perform all-atom
      explicit-water molecular dynamics (MD) simulations to study the orientation
      change, conformational dynamics, surface interaction of small Abeta aggregates
      with different sizes (monomer to tetramer), and conformations (alpha-helix and
      beta-hairpin) upon adsorption on the graphite surface, in comparison with Abeta
      structures in bulk solution. Simulation results show that hydrophobic graphite
      induces the quick adsorption of Abeta peptides regardless of their initial
      conformations and sizes. Upon the adsorption, Abeta prefers to adopt random
      structure for monomers and to remain beta-rich-structure for small oligomers, but
      not helical structures. More importantly, due to the amphiphilic sequence of
      Abeta and the hydrophobic nature of graphite, hydrophobic C-terminal residues of
      higher-order Abeta oligomers appear to have preferential interactions with the
      graphite surface for facilitating Abeta fibril formation and fibril growth. In
      combination of atomic force microscopy (AFM) images and MD simulation results, a
      postulated mechanism is proposed to describe the structure and kinetics of Abeta
      aggregation from aqueous solution to the graphite surface, providing parallel
      insights into Abeta aggregation on biological cell membranes. 

PMID- 22468637
TI  - Linkage of topiramate and the central corneal thickening.

PMID- 22468638
TI  - Up to 4 orders of magnitude enhancement of crown ether complexation in an aqueous
      phase coexistent with ice.
AB  - Ice chromatography measurements have revealed anomalous enhancements of crown
      ether complexation in a liquid phase coexistent with ice. The 4 orders of
      magnitude enhancement was confirmed for the complexation of dibenzo-24-crown-8 in
      sub-MUm-sized liquid inclusions formed in ice doped with <1 mM NaCl or KCl. This
      enhancement became less pronounced with increasing dopant concentration.

PMID- 22468639
TI  - Design and preparation of a potent series of hydroxyethylamine containing beta
      secretase inhibitors that demonstrate robust reduction of central beta-amyloid.
AB  - A series of potent hydroxyethyl amine (HEA) derived inhibitors of beta-site APP
      cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and
      poor CNS partitioning. This work identified a series of benzodioxolane analogues
      that possessed improved metabolic stability and increased oral bioavailability.
      Subsequent efforts focused on improving CNS exposure by limiting susceptibility
      to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and
      sustained reduction of CNS beta-amyloid (Abeta) in Sprague-Dawley rats following
      oral administration.

PMID- 22468640
TI  - Investigation of parvovirus B19 seroprevalence, endothelin-1 synthesis, and
      nitric oxide levels in the etiology of essential hypertension.
AB  - BACKGROUND AND AIMS: Many studies have focused on the role of pathogen infection
      in hypertension (HT). It has been postulated that increased vascular tonus in HT
      is basically related to the imbalance between vasodilator, such as nitric oxide
      (NO), and vasoconstrictor, such as endothelin-1 (ET-1), substances secreted by
      endothelium. The aim of the present study was to investigate the seroprevalence
      of human parvovirus B19 (HPV B19) in the etiology of essential HT and the effect
      of HPV B19 on ET-1 and NO levels in this disorder. MATERIALS AND METHODS: A total
      of 135 participants were enrolled in the study (90 patient and 45 controls).
      Antibodies to HPV B19 and ET-1 were measured by enzyme-linked immunosorbent assay
      method. Nitric oxide levels were calculated according to the Griess reaction.
      RESULTS: Of the total participants, 27 patients (30%) and 7 control subjects
      (15.6%) had IgM positive (P = .068), whereas 27 patients (30%) and 14 control
      subjects (31.1%) had IgG positive (P = .895). There was no statistical difference
      between patients and control subjects in terms of serum ET-1 and NO levels.
      CONCLUSIONS: The role of HPV B19 in the etiology of essential HT was not shown in
      the present study. A larger sample may be needed for the investigation of these
      relations.

PMID- 22468641
TI  - Peptide-decorated liposomes promote arrest and aggregation of activated platelets
      under flow on vascular injury relevant protein surfaces in vitro.
AB  - Platelet-mimetic synthetic hemostats are highly attractive in transfusion
      medicine. To this end, past research reports have described particles that either
      amplify platelet aggregation or mimic platelet adhesion. However, a construct
      design that effectively combines both functionalities has not been reported. Here
      we describe the design of a liposomal construct simultaneously surface-decorated
      with three peptides (a vWF-binding peptide (VBP), a collagen-binding peptide
      (CBP), and an active platelet clustering cyclic-RGD (cRGD) peptide), that can
      integrate platelet-mimetic dual hemostatic activities of adhesion and
      aggregation. We first demonstrate that surface-immobilized cRGD-liposomes are
      capable of aggregating activated platelets onto themselves. Subsequently, we
      demonstrate that hetero-multivalent liposomes bearing VBP, CBP, and cRGD, when
      introduced in flow with ~ 20,000 activated platelets per microliter, are capable
      of adhering to vWF/collagen surfaces and promoting the recruitment/aggregation of
      platelets onto themselves. We envision that optimizing this construct can lead to
      a highly refined synthetic hemostat design for potential application in
      transfusion medicine.

PMID- 22468642
TI  - New genus of Cosmocercidae (Nematoda) and other helminths in Hylarana volkerjane
      (Anura: Ranidae) from Papua New Guinea.
AB  - Paraplesiohedruris rinse n. gen., n. sp. (Ascaridida; Cosmocercoidae;
      Cosmocercidae) from the large intestine of Hylarana volkerjane (Anura; Ranidae)
      is described and illustrated. The new genus is assigned to the Cosmocercinae of
      the Cosmocercidae based on the presence of an esophagus composed of a short
      pharynx, cylindrical corpus, isthmus, and valved bulb; on the presence in males
      of paired spicules and numerous caudal papillae; plus the presence in the female
      of an equatorial vulva, 2 uteri, a short tail, and thin-shelled eggs. The
      Cosmocercinae now contains 10 genera. Hylarana volkerjane was also found to
      harbor 6 additional species of Nematoda, adults of Aplectana macintoshii,
      Icosiella papuensis, Meteterakis crombiei, Paracapillaria spratti,
      Physalopteroides milnensis, and larvae of Abbreviata sp., as well as 1 species of
      Acanthocephala, Pseudoacanthocephalus bufonis.

PMID- 22468644
TI  - Coherence and other autistic spectrum traits and eating disorders: building from
      mechanism to treatment. The Birgit Olsson lecture.
AB  - AIM: To revisit Gillberg's hypothesis proposed in 1992, which was that anorexia
      nervosa should be considered within the spectrum of autistic disorders. METHOD: A
      search was made of the literature relating to the behavioural traits, and
      cognitive, emotional and neuroanatomical intermediate phenotypes that are shared
      between autistic spectrum disorders (ASD) and anorexia nervosa. RESULTS: People
      with eating disorders in the acute phase (less so after recovery) share some
      behavioural traits (social impairment and restricted and repetitive behaviours)
      and intermediate phenotypes (weak central coherence, and impaired set shifting
      and theory of mind) with people in the autistic spectrum. CONCLUSION: Behavioural
      and intermediate neuropsychological traits are shared between eating disorders
      and ASD. In part, these are familial but also they are accentuated by the illness
      state and may be secondary to starvation. These traits have implications for
      prognosis and treatment.

PMID- 22468643
TI  - OnabotulinumtoxinA (BOTOX(r)): a review of its use in the prophylaxis of
      headaches in adults with chronic migraine.
AB  - This article reviews the pharmacology, therapeutic efficacy and tolerability
      profile of intramuscularly injected onabotulinumtoxinA (onaBoNTA; BOTOX(r)) for
      headache prophylaxis in adults with chronic migraine, with a focus on UK
      labelling for the drug. The pharmacological actions of onaBoNTA include a direct
      antinociceptive (analgesic) effect; while not fully understood, the mechanism of
      action underlying its headache prophylaxis effect in chronic migraine is presumed
      to involve inhibition of peripheral and central sensitization in
      trigeminovascular neurones. Pooled findings from two large phase III studies of
      virtually identical design (PREEMPT [Phase III REsearch Evaluating Migraine
      Prophylaxis Therapy] 1 and 2) showed that treatment with up to five cycles of
      onaBoNTA (155-195 units/cycle) at 12-week intervals was effective in reducing
      headache symptoms, decreasing headache-related disability, and improving health
      related quality of life (HR-QOL) in patients with chronic migraine, approximately
      two-thirds of whom were overusing acute headache medications at baseline. During
      the double-blind phase of both trials, significantly more patients treated with
      onaBoNTA (two cycles) than placebo experienced clinically meaningful improvements
      in the monthly frequencies of headache days, moderate to severe headache days and
      migraine days, and in the cumulative hours of headache on headache days/month.
      OnaBoNTA therapy also resulted in statistically significant and clinically
      meaningful improvements in functioning and HR-QOL compared with placebo. Notably,
      improvements in headache symptoms, functioning and HR-QOL favouring onaBoNTA over
      placebo were seen regardless of whether or not patients were medication overusers
      and irrespective of whether or not they were naive to (oral) prophylactic
      therapy. Further improvements relative to baseline in headache symptoms,
      functioning and HR-QOL were observed during the open-label extension phase of
      both trials (all patients received three cycles of onaBoNTA). Treatment with up
      to five cycles of onaBoNTA was generally well tolerated in the PREEMPT trials.
      Treatment-related adverse events reported by onaBoNTA recipients (e.g. neck pain,
      facial paresis and eyelid ptosis) were consistent with the well established
      tolerability profile of the neurotoxin when injected into head and neck muscles;
      no new safety events were observed. Debate surrounding the PREEMPT studies has
      centred on the small treatment effect of onaBoNTA relative to placebo, the
      possibility that blinding was inadequate and the relevance of the evaluated
      population. Nonetheless, the totality of the data showed that onaBoNTA therapy
      produced clinically meaningful improvements in headache symptoms, functioning and
      HR-QOL; on the basis of these trials, it has become the first (and so far only)
      headache prophylactic therapy to be specifically approved for chronic migraine in
      the UK and US. Overall, onaBoNTA offers a beneficial, acceptably tolerated and
      potentially convenient option for the management of this highly disabling
      condition, for example in patients who are refractory to oral medications used
      for prophylaxis.

PMID- 22468645
TI  - Royal jelly increases collagen production in rat skin after ovariectomy.
AB  - Royal jelly (RJ) is a honeybee product that contains proteins, carbohydrates,
      fats, free amino acids, vitamins, and minerals. RJ has been reported to have
      antitumor, antibacterial, and wound-healing activities. We previously reported
      that RJ enhanced the migration of human dermal fibroblasts and altered the levels
      of cholesterol and sphinganine in an in vitro wound-healing model in addition to
      regulating skin photoaging following exposure to ultraviolet-B radiation. We
      established an animal model of skin aging in the context of estrogen deficiency
      and assessed the antiaging effects of RJ on skin. To establish an in vivo model
      of skin aging, bilateral ovariectomies were performed in 12-week-old virgin
      female Sprague-Dawley rats. Induction of osteoporosis was confirmed through two
      dimensional images of the trabecular bone in the left femoral necks using
      microcomputed tomography. The protective effects of RJ ovariectomy-induced skin
      aging were examined by determining the protein expression of type I procollagen
      and matrix metalloproteinase (MMP)-1. The collagen content and epidermal
      thickness of skin tissue were measured by staining techniques. There was a
      significant difference in weight between sham-operated and ovariectomized groups.
      Food efficiency ratio did not differ significantly among the groups. The level of
      procollagen type I protein was increased in the dorsal skin of ovariectomized
      rats fed with a dietary supplement containing 1% RJ extract, but the level of MMP
      1 was not altered. In particular, the amount of collagen recovered was close to
      the normal level. RJ may protect against skin aging by enhancing collagen
      production in rats with ovariectomy-induced estrogen deficiency.

PMID- 22468646
TI  - Bactericidal activity of soymilk fermentation broth by in vitro and animal
      models.
AB  - Soybean fermentation broth (SFB) exhibits potent antibacterial activity against
      different species of bacteria in in vitro assays and animal models. Four
      isoflavone compounds-daidzin, genistin, genistein, and daidzein-of SFB were
      analyzed and quantified by high-performance liquid chromatography. In the in
      vitro test, daidzin and daidzein had more potent antibacterial activity than
      genistin. The minimum inhibition concentration values for these bacteria of SFB
      ranged from 1.25% to 5%, and the minimum bactericidal concentration values of
      strains ranged from 2.5% to 10%, depending on the species or strain. Vancomycin
      resistant Entercoccus faecalis (VRE) strains were also tested for susceptibility
      to SFB in two species of animal model: the Sprague-Dawley rat and the BALB/c
      mouse. SFB-fed Sprague-Dawley rats showed excellent elimination efficiency
      against VRE, close to 99% compared with the phosphate-buffered saline-fed control
      group. In the BALB/c mouse model, SFB antibacterial activity was 65-80% against
      VRE compared with the control. In conclusion, SFB contains natural antibacterial
      substances such as daidzin, genistin, and daidzein that inhibit bacterial growth.

PMID- 22468647
TI  - Ferric complexes of 3-hydroxy-4-pyridinones characterized by density functional
      theory and Raman and UV-vis spectroscopies.
AB  - Deferiprone and other 3-hydroxy-4-pyridinones are used in metal chelation therapy
      of iron overload. To investigate the structure and stability of these compounds
      in the natural aqueous environment, ferric complexes of deferiprone and amino
      acid maltol conjugates were synthesized and studied by computational and optical
      spectroscopic methods. The complexation caused characteristic intensity changes,
      a 300* overall enhancement of the Raman spectrum, and minor changes in UV-vis
      absorption. The spectra were interpreted on the basis of density functional
      theory (DFT) calculations. The CAM-B3LYP and omegaB97XD functionals with CPCM
      solvent model were found to be the most suitable for simulations of the UV-vis
      spectra, whereas B3LYP, B3LYPD, B3PW91, M05-2X, M06, LC-BLYP, omegaB97XD, and CAM
      B3LYP functionals were all useful for simulation of the Raman scattering.
      Characteristic Raman band frequencies for 3-hydroxy-4-pyridinones were assigned
      to molecular vibrations. The computed conformer energies consistently suggest the
      presence of another isomer of the deferiprone-ferric complex in solution, in
      addition to that found previously by X-ray crystallography. However, the UV-vis
      and Raman spectra of the two species are similar and could not be resolved. In
      comparison to UV-vis, the Raman spectra and their combination with calculations
      appear more promising for future studies of iron sequestrating drugs and
      artificial metalloproteins as they are more sensitive to structural details.

PMID- 22468648
TI  - A versatile targeted metabolomics method for the rapid quantification of multiple
      classes of phenolics in fruits and beverages.
AB  - Compelling evidence of the health benefits of phenolic compounds and their impact
      on food quality have stimulated the development of analytical methods for the
      identification and quantification of these compounds in different matrices in
      recent years. A targeted metabolomics method has been developed for the
      quantification of 135 phenolics, such as benzoates, phenylpropanoids, coumarins,
      stilbenes, dihydrochalcones, and flavonoids, in fruit and tea extracts and wine
      using UPLC/QqQ-MS/MS. Chromatography was optimized to achieve separation of the
      compounds over a period of 15 min, and MRM transitions were selected for accurate
      quantification. The method was validated by studying the detection and
      quantification limits, the linearity ranges, and the intraday and interday
      repeatability of the analysis. The validated method was applied to the analysis
      of apples, berries, green tea, and red wine, providing a valuable tool for food
      quality evaluation and breeding studies.

PMID- 22468649
TI  - Building blocks for oligospiroketal (OSK) Rods and evaluation of their influence
      on rod rigidity.
AB  - We report on the synthesis of three new sleeves and their incorporation in OSK
      rods. The structures of these sleeves are based on neo-inositol,
      terephthalaldehyde diacetals, and indacene. To quantify the influence of the
      sleeves on rod rigidity, we applied the worm-like chain (WLC) model on the new
      rods and found that this approach is rather disappointing. As the chief cause of
      this result, we assume that the rigidity of typical molecular rods largely
      exceeds the rigidity of polymers, which were successfully described by the WLC
      model. Alternatively, we suggest quantifying the rigidity of molecular rods by
      fitting an empirical function on the end-to-end distance distribution curve
      obtained by MD simulations. After checking various function types, the Levy
      Martin function proved to be most suitable for this purpose. On the basis of this
      function, we defined the Levy-Martin parameter and suggest using this parameter
      for the characterization of the rigidity of molecular rods.

PMID- 22468651
TI  - Mechanistic insights into the hydrolysis of a nucleoside triphosphate model in
      neutral and acidic solution.
AB  - Nucleoside triphosphate hydrolysis is an essential component of all living
      systems. Despite extensive research, the exact modus and mechanism of this
      ubiquitous reaction still remain elusive. In this work, we examined the detailed
      hydrolysis mechanisms of a model nucleoside triphosphate in acidic and neutral
      solution by means of ab initio simulations. The timescale of the reaction was
      accessed through use of an accelerated sampling method, metadynamics. Both
      hydrolyses were found to proceed via different mechanisms; the acidic system
      reacted by means of concerted general acid catalysis (found to be a so-called
      D(N)A(N)A(H)D(xh) mechanism), whereas the neutral system reacted by way of a
      different mechanism (namely, D(N)*A(N)D(xh)A(H)). A neighboring water molecule
      took on the role of a general base in both systems, which has not been seen
      before but is a highly plausible reaction path, meaning that substrate-assisted
      catalysis was not observed in the bulk water environment.

PMID- 22468650
TI  - DNA damage of macrophages induced by metal nanoparticulates using an air-liquid
      interface exposure model.

PMID- 22468652
TI  - Crossover from spin-flop coupling to collinear spin alignment in
      antiferromagnetic/ferromagnetic nanostructures.
AB  - The technologically important exchange coupling in
      antiferromagnetic/ferromagnetic bilayers is investigated for embedded
      nanostructures defined in a LaFeO(3)/La(0.7)Sr(0.3)MnO(3) bilayer. Exploiting the
      element specificity of soft X-ray spectromicroscopy, we selectively probe the
      magnetic order in the two layers. A transition from perpendicular to parallel
      spin alignment is observed for these nanostructures, dependent on size and
      crystalline orientation. The results show that shape-induced anisotropy in the
      antiferromagnet can override the interface exchange coupling in spin-flop coupled
      nanostructures.

PMID- 22468653
TI  - Novel approach to test the relative recovery of liquid-phase standard in sorbent
      tube analysis of gaseous volatile organic compounds.
AB  - Sorbent tubes (STs) are highly efficient and versatile tools for collecting
      gaseous samples of volatile organic compounds (VOCs). In order to assess the
      experimental bias in their application, the relative recovery (RR) of 19 VOCs
      (acetaldehyde, propionaldehyde, butyraldehyde, isovaleraldehyde, valeraldehyde,
      benzene, toluene, m-xylene, p-xylene, o-xylene, styrene, methyl ethyl ketone,
      methyl isobutyl ketone, isobutyl alcohol, butyl acetate, propionic acid, butyric
      acid, isovaleric acid, and n-valeric acid) was evaluated in accordance to three
      different sorbent tube types: (1) Tenax (Te), (2) Carbopack X (X), and (3) Tenax
      + Carbopack B + Carboxen 1000 (TBC). Calibration was initially made by direct
      injection of the liquid working standard (L-WS) into the link tube (LT) of the
      thermal desorption (TD) system. The LT was modified to optimize the transfer of
      all the VOCs to the focusing trap of the TD. Three different types of ST were
      then loaded with the same L-WS using (1) direct injection (DI) to tube and (2)
      injection to tube via vaporization (VAP). The results of the two ST/TD methods
      (DI and VAP) were normalized to those of the LT/TD to derive RR. The mean RR
      values of all target VOCs were 62.6 (X), 83.9 (Te), and 82.8% (TBC) for the DI
      and 76.5, 75.8, and 81.0% for the VAP. Although the results using TBC and Te
      tubes exhibited better recovery in DI than in VAP, those of X tubes had the
      reverse trend. As such, the relative affinity of each sorbent material can be
      affected by the mode of introduction of the standard. The practicality of the
      LT/TD, especially as a reference for the ST/TD, was also validated from some
      environmental samples in an ancillary experiment. As such, we were able to
      demonstrate the usefulness of the LT/TD method to evaluate analyte recovery from
      spiked sorbent tubes.

PMID- 22468654
TI  - Offering more than hope to the incarcerated population.

PMID- 22468655
TI  - Substance abuse prevention and treatment within the criminal justice system: an
      overview of the issues.
AB  - Many nurses, especially those in addictions, work directly in the prison system
      and or relate to inmates before or after institutionalization for criminal
      activity. This connection led to the theme of the 2009 Annual Education
      Conference held in Albuquerque, New Mexico, entitled "Substance Abuse Prevention
      and Treatment: Working with the Criminal Justice Systems." The conference was
      partially funded through an award from the Substance Abuse and Mental Health
      Services Administration (SAMHSA), Center for Substance Abuse Prevention (grant #
      SP015963) and focused on identifying the special risk factors for and barriers to
      the treatment of addictions for those who enter the criminal justice system. The
      conference, presented in collaboration with the American Association of Nurse
      Attorneys (AANA) highlighted the tremendous need for more access to addictions
      and mental health providers in the criminal justice system. Papers presented at
      that conference confirmed that nurses can make a real difference in the health of
      inmates, especially those of us engaged in addictions and mental health
      practices, and inspired this specially focused edition of the Journal of
      Addictions Nursing. The purpose of this editorial is to provide an overview of
      the addictions problems affecting individuals under supervision in the criminal
      justice system, barriers to treatment within this system, and the cost-benefits
      of evidence based treatment.

PMID- 22468656
TI  - A research-practice partnership for enhancing drug court effectiveness.
AB  - Research and practice partnerships that focus on substance use and criminal
      justice are necessary to address the needs and concerns of substance users, their
      families, and the community. Such partnerships are complex and therefore create
      challenges in implementing research that is simultaneously relevant and rigorous.
      This article describes a developing research-practice community-based partnership
      that guides several related research studies. Lessons learned, implications for
      nursing, and practical recommendations for others in forming such partnerships
      are offered.

PMID- 22468657
TI  - Addictions and the criminal justice system, what happens on the other side? Post
      traumatic stress symptoms and cortisol measures in a police cohort.
AB  - The Buffalo Cardio-metabolic Occupational Police Stress study, an occupational
      cohort study of police officers, was conducted to evaluate physiologic and stress
      measures in a high-risk occupation where occupational exposure to difficult
      criminal situations can lead to physiologic and psychological health consequences
      among those who enforce the law. The chronic exposure to human tragedy may place
      police officers at special risk for mental health disorders and the potential for
      misuse of alcohol or drugs. While exact etiologies of post-traumatic stress were
      not determined by this study, overall post-traumatic stress (PTS) prevalence
      rates among the police officers was 35%, with 10% of individuals demonstrating
      severe PTS symptomatology. Waking cortisol measures tended to be higher among
      officers with more PTS symptomatology, with some gender related differences
      noted. Given the increase in incarcerations for addictions related offenses over
      the past 20 years and the chronic exposure to human suffering and tragedy, early
      recognition of PTS symptoms is essential in making the diagnosis of post
      traumatic stress in high-risk occupational cohorts. Providing early entry into
      treatment and subsequently attempting to eliminate or minimize long-term
      consequences of post-traumatic stress can have a significant impact on the
      prevention of long term sequelae of chronic stress, such as the use or misuse of
      drugs or alcohol.

PMID- 22468658
TI  - The informational yield of paired samples from a large sample: hair analysis and
      urinalysis for cocaine and cannabinoids.
AB  - In a variety of decision settings when categorical information is the data in
      hand, the correspondence between an indicator test and a true condition (i.e., an
      accepted "gold standard") is often assessed by the use of comparison or "truth"
      tables. The results from such a table can be considered an informational yield
      and allow a practitioner to assess the utility of the indicator test in various
      ways, such as specificity and sensitivity, false positive and negative rates, and
      the positive and negative predictive values. There are many reasons for the use
      of an indicator test. This article proposes a novel application of an
      informational measure in determining the utility of hair and urine specimens for
      clinical decision making. It does this for two commonly abused substances,
      cocaine and cannabinoids. It suggests that in clinical applications the ability
      to assess informational yield is an important factor in developing clinical
      strategies for treatment of addictive disorders.

PMID- 22468659
TI  - Standards for opioid treatment in the criminal justice system: implications for
      nurses.
AB  - The delivery of health care is based on the theory that patients have timely
      access to qualified clinicians who will render a professional clinical judgment
      that is ordered and received. This article describes traditional barriers to
      opioid treatment and care to incarcerated populations. With 60 to 80 percent of
      current and former prisoners convicted on drug-related charges, the need to
      provide drug abuse treatment in jails and prisons remains a high social and
      clinical priority. The medical, economic, and social burden of opioid addiction
      can be alleviated with the expansion of addiction treatment programming in the
      criminal justice system. This article presents arguments why this programming
      should be implemented and describes national standards on how services should be
      organized. The article concludes with a description of the nursing role in a
      criminal justice substance abuse program highlighting key tasks that correctional
      nurses perform. The article concludes with a discussion of the future challenges
      and directions to opioid treatment in the criminal justice system.

PMID- 22468660
TI  - Labyrinth walking in corrections.
AB  - A 6 week labyrinth walking program was pilot tested in a correctional setting and
      goals were to: 1) determine the feasibility of a labyrinth walking curriculum; 2)
      pilot test measures of health related quality of life (QOL) (pre and post
      surveys) and blood pressure; and 3) examine the influence of relationship
      centered teaching on subject satisfaction. Relational communication was used as a
      framework for this study, emphasizing concepts of trust, competency and similarly
      in the teacher. A pretest/posttest descriptive design was used. The sample was 14
      offenders at a Massachusetts county jail. The intervention included six 90 minute
      sessions, composed of a lecture, a labyrinth walk, and journal writing. Measures
      included a demographic survey; pre and post session walk blood pressures; pre and
      post program QOL measures; and a post program measure of satisfaction. The sample
      was 57% Caucasian, 36% Hispanic, and 7% African American, with an average age of
      34, mostly high school educated and single. Drug of choice was alcohol with age
      of use at 12 and 1/2 years. Seventy-nine percent were previously incarcerated
      more than twice. QOL data were not changed pre to post. BP data trended in a
      healthy direction from weeks 1 to 6. Satisfaction with the teacher and the
      program was high. The labyrinth walking pilot program was proven feasible, low
      cost and satisfying for the participants. Recommendations for future studies are
      discussed.

PMID- 22468661
TI  - High-risk situations related to relapse of methamphetamine use among Taiwanese
      adolescents: an instrumentation study.
AB  - Methamphetamine is the leading illicit substance used by adolescents in Taiwan
      and the rise of its production and use is a major public health concern in
      Southeast and East Asia. The purpose of this study was to develop and test a new
      instrument to identify high-risk situations related to methamphetamine relapse
      among incarcerated Taiwanese adolescents. Participants in this study were
      arrested for methamphetamine use and mandatorily held at an abstinence center. In
      the instrument development phase, an item pool was generated from a qualitative
      study and further revised based on content evaluations by 6 clinical content
      experts. In the instrument analysis phase, the new tool was psychometrically
      tested. The intra-class correlation coefficient showed high stability of the
      instrument (r = .92). Factor analysis resulted in a 6-factor solution accounting
      for 66.68% of the variance in the 16-item model. Although this instrument was
      developed for use with Taiwanese adolescents, it needs further testing to confirm
      its usefulness in other cultural groups. The identified risky situations provide
      a beginning assessment tool that is easy to administer and can be used to
      identify teens at particular risk for relapse before being released from
      incarceration or other mandatory treatment programs. More research is needed to
      target specific and culturally determined triggers that can improve the validity
      of this tool for non Asian adolescents at risk for methamphetamine relapse.

PMID- 22468662
TI  - Wellbutrin(r): misuse and abuse by incarcerated individuals.
AB  - Misuse and abuse of prescription medications is increasing across both
      socioeconomic and age parameters. This article includes a review of the uses of
      Wellbutrin(r), and its current misuse/abuse within the correctional setting. It
      includes a discussion regarding the pharmacodynamics involved in substance abuse.
      A review of current literature includes both academic research and public forums
      regarding this topic. It also discusses the role of dopamine in both
      Wellbutrin(r) and substance use. The author identifies the lack of current
      research regarding this topic and poses ethical questions for the provider.

PMID- 22468663
TI  - Alcohol and tobacco related health inequity: a population health perspective.

PMID- 22468665
TI  - Peer assistance in New York State: Statewide Peer Assistance for Nurses (SPAN).

PMID- 22468666
TI  - Buprenorphine prescribing by APRNs.

PMID- 22468667
TI  - The prescribing of buprenorphine by advanced practice addictions nurses.
AB  - In order to increase safe access to buprenorphine treatment for patients with
      opioid dependence, it is the position of the International Nurses Society on
      Addictions (IntNSA) that the Drug Addiction Treatment Act of 2000 (DATA 2000) be
      amended to allow for the prescribing of buprenorphine by qualified advanced
      practice nurses who have both prescriptive authority and specialty certification
      in addictions nursing.

PMID- 22468668
TI  - The nature of experience determines object representations in the visual system.
AB  - Visual perceptual learning (PL) and perceptual expertise (PE) traditionally lead
      to different training effects and recruit different brain areas, but reasons for
      these differences are largely unknown. Here, we tested how the learning history
      influences visual object representations. Two groups were trained with tasks
      typically used in PL or PE studies, with the same novel objects, training
      duration and parafoveal stimulus presentation. We observed qualitatively
      different changes in the cortical representations of these objects following PL
      and PE training, replicating typical training effects in each field. These
      effects were also modulated by testing tasks, suggesting that experience
      interacts with attentional set and that the choice of testing tasks critically
      determines the pattern of training effects one can observe after a short-term
      visual training. Experience appears sufficient to account for prior differences
      in the neural locus of learning between PL and PE. The nature of the experience
      with an object's category can determine its representation in the visual system.

PMID- 22468669
TI  - The role of mind-wandering in measurements of general aptitude.
AB  - Tests of working memory capacity (WMC) and fluid intelligence (gF) are thought to
      capture variability in a crucial cognitive capacity that is broadly predictive of
      success, yet pinpointing the exact nature of this capacity is an area of ongoing
      controversy. We propose that mind-wandering is associated with performance on
      tests of WMC and gF, thereby partially explaining both the reliable correlations
      between these tests and their broad predictive utility. Existing evidence
      indicates that both WMC and gF are correlated with performance on tasks of
      attention, yet more decisive evidence requires an assessment of the role of
      attention and, in particular, mind-wandering during performance of these tests.
      Four studies employing complementary methodological designs embedded thought
      sampling into tests of general aptitude and determined that mind-wandering was
      consistently associated with worse performance on these measures. Collectively,
      these studies implicate the capacity to avoid mind-wandering during demanding
      tasks as a potentially important source of success on measures of general
      aptitude, while also raising important questions about whether the previously
      documented relationship between WMC and mind-wandering can be exclusively
      attributed to executive failures preceding mind-wandering (McVay & Kane, 2010b).

PMID- 22468670
TI  - Unconscious evaluation of faces on social dimensions.
AB  - It has been proposed that two major axes, dominance and trustworthiness,
      characterize the social dimensions of face evaluation. Whether evaluation of
      faces on these social dimensions is restricted to conscious appraisal or happens
      at a preconscious level is unknown. Here we provide behavioral evidence that such
      preconscious evaluations exist and that they are likely to be interpretations
      arising from interactions between the face stimuli and observer-specific traits.
      Monocularly viewed faces that varied independently along two social dimensions of
      trust and dominance were rendered invisible by continuous flash suppression (CFS)
      when a flashing pattern was presented to the other eye. Participants pressed a
      button as soon as they saw the face emerge from suppression to indicate whether
      the previously hidden face was located slightly to the left or right of central
      fixation. Dominant and untrustworthy faces took significantly longer time to
      emerge (T2E) compared with neutral faces. A control experiment showed these
      findings could not reflect delayed motor responses to conscious faces. Finally,
      we showed that participants' self-reported propensity to trust was strongly
      predictive of untrust avoidance (i.e., difference in T2E for untrustworthy vs
      neutral faces) as well as dominance avoidance (i.e., difference in T2E for
      dominant vs neutral faces). Dominance avoidance was also correlated with
      submissive behavior. We suggest that such prolongation of suppression for
      threatening faces may result from a passive fear response, leading to slowed
      visual perception.

PMID- 22468671
TI  - Improving the past and the future: a temporal asymmetry in hypothetical thinking.
AB  - Current views of hypothetical thinking implicitly assume that the content of
      imaginary thoughts about the past and future should be the same. Two experiments
      show that, given the same experienced facts of reality, future imagination may
      differ from past reconstruction. When participants failed a task, their
      counterfactual thoughts focused on uncontrollable features of their attempt
      (e.g., "Things would have been better if the allocated time were longer/if I had
      better logic skills"). But their prefactual thoughts focused on controllable
      features of their ensuing endeavor (e.g., "Things will be better next time if I
      concentrate more/if I use another strategy"). This finding suggests that compared
      with prefactual thinking, counterfactual thinking may be less subject to reality
      checks and less likely to serve preparatory goals.

PMID- 22468672
TI  - Adaptive reward pursuit: how effort requirements affect unconscious reward
      responses and conscious reward decisions.
AB  - When in pursuit of rewards, humans weigh the value of potential rewards against
      the amount of effort that is required to attain them. Although previous research
      has generally conceptualized this process as a deliberate calculation, recent
      work suggests that rudimentary mechanisms-operating without conscious
      intervention-play an important role as well. In this article, we propose that
      humans can perform a basic integration of reward value and effort requirements
      without conscious awareness. Furthermore, we propose that conscious awareness of
      rewards allows for the use of more advanced functions in reward pursuit, which
      consider the specific course of action that leads to reward attainment. Using a
      monetary reward priming paradigm that allows us to dissect the performance
      effects of rewards (i.e., coins of different value) into conscious and
      unconscious components, we tested this proposal in 3 experiments. Overall,
      results indicate that people rely on a simple yet adaptive mechanism that
      unconsciously conserves effort during reward pursuit, because it makes people
      more reward sensitive whenever more effort is required of the body. Moreover,
      consciousness supports a more sophisticated mode of reward pursuit, via which
      people can strategically conserve effort even further. We discuss these findings
      in the context of decision making, motivation, and consciousness.

PMID- 22468673
TI  - Folate malabsorption and its influence on DNA methylation during cancer
      development.
AB  - The folate transport across the epithelial of the intestine, colon, kidney, and
      liver is essential for folate homeostasis. The relative localization of
      transporters in membranes is an important determinant for the vectorial flow of
      substrates across the epithelia. Folate deficiency is a highly prevalent vitamin
      deficiency in the world, and alcohol ingestion has been the major contributor. It
      can develop because of folate malabsorption in tissues, increased renal excretion
      dietary inadequacy, and altered hepatobiliary metabolism. Additionally, folate
      mediated one-carbon metabolism is important for various cellular processes,
      including DNA synthesis and methylation. In this regard, the contribution of
      alcohol-associated and dietary folate deficiency to methylation patterns is under
      intense investigation, especially in cancer. The epigenetic events have
      increasing relevance in the development of strategies for early diagnosis,
      prevention, and treatment of cancer. 

PMID- 22468674
TI  - DNA interaction studies of a copper (II) complex containing an antiviral drug,
      valacyclovir: the effect of metal center on the mode of binding.
AB  - The water-soluble complex, [Cu(Val)(2)(NO(3))(2)]; in which Val = valacyclovir,
      an antiviral drug, has been synthesized and characterized by elemental analysis,
      furier transfer-infrared, hydrogen nuclear magnetic resonance (H NMR), and UV-Vis
      techniques. The binding of this Cu (II) complex to calf thymus DNA was
      investigated using fluorimetry, spectrophotometry, circular dichroism, and
      viscosimetry. In fluorimetric studies, the enthalpy and entropy of the reaction
      between the complex and calf-thymus DNA (CT-DNA) showed that the reaction is
      endothermic (DeltaH = 208.22 kJ mol(-1); DeltaS = 851.35 J mol(-1)K(-1)). The
      complex showed the absorption hyperchromism in its ultra violet-visible (UV-Vis)
      spectrum with DNA. The calculated binding constant, K(b), obtained from UV-Vis
      absorption studies was 2 * 10(5) M(-1). Moreover, the complex induced detectable
      changes in the circular dichroism spectrum of CT-DNA, as well as changes in its
      viscosity. The results suggest that this copper (II) complex interacts with CT
      DNA via a groove-binding mode.

PMID- 22468675
TI  - Regional differences and similarities of FAP in Sweden.
AB  - Marked differences in phenotype in familial amyloid polyneuropathy (FAP)
      populations have been noted between but also within FAP populations. Initially,
      it was believed that patients with FAP, caused by the TTR V30M mutation, shared
      the same founder. However, recent studies have clearly shown that the V30M
      mutation in Sweden occurred spontaneously later in time than that in Portugal.
      The Swedish FAP-population's phenotype differs between various areas within
      northern Sweden. Thus the age at onset is in average 20 years earlier in
      Skelleftea than in Pitea areas, a distance of only 60 km. Age at onset appears
      also to have an impact on complications of the disease. Late-onset cases often
      develop a cardiomyopathy, especially male patients. Mitochondrial haplotype
      distribution has been noted to differ between early- and late- onset patients in
      the Swedish population. Mitochondrial function is one possible factor
      contributing to the differences seen both between and within populations.

PMID- 22468676
TI  - Drug safety evaluation of  rotigotine.
AB  - INTRODUCTION: Rotigotine, a non-ergolinic dopamine-receptor agonist, is currently
      approved as monotherapy in early idiopathic Parkinson's disease (IPD), in
      moderate to severe idiopathic restless legs syndrome (RLS) and as adjunct therapy
      to levodopa in advanced IPD. Randomized, double-blind, placebo-controlled, as
      well as open-label studies were conducted in IPD and RLS patients to evaluate the
      efficacy, tolerability and safety of rotigotine in dosages up to 16 mg/24 h.
      Overall, these trials have shown that rotigotine has a similar adverse event (AE)
      profile as other non-ergolinic dopamine agonists such as pramipexole or
      ropinirole, inducing typical dopaminergic effects like nausea, daytime
      somnolence, peripheral edema or impulse control disorders. In addition, the most
      common AE seen with transdermal delivery of rotigotine are local skin reactions,
      which may lead to a treatment discontinuation in approximately 8% of patients.
      AREAS COVERED: This review outlines Phase II and III trials that were published
      between 2003 and 2011. The focus of this review is on the safety profile of
      rotigotine but it also goes into detail about clinical trial data,
      pharmacokinetics and pharmacodynamics. EXPERT OPINION: The emergent safety
      profile is similar to other non-ergolinic dopamine agonists. In addition,
      transdermal delivery is associated with local skin reactions, which are usually
      mild but may lead to a treatment discontinuation in a minority of patients.

PMID- 22468677
TI  - An automaton approach for waiting times in DNA evolution.
AB  - In a recent article, Behrens and Vingron (J. Comput. Biol. 17/12, 2010) compute
      waiting times for k-mers to appear during DNA evolution under the assumption that
      the considered k-mers do not occur in the initial DNA sequence, an issue arising
      when studying the evolution of regulatory DNA sequences with regard to
      transcription factor (TF) binding site emergence. The mathematical analysis
      underlying their computation assumes that occurrences of words under interest do
      not overlap. We relax here this assumption by use of an automata approach. In an
      alphabet of size 4 like the DNA alphabet, most words have no or a low
      autocorrelation; therefore, globally, our results confirm those of Behrens and
      Vingron. The outcome is quite different when considering highly autocorrelated k
      mers; in this case, the autocorrelation pushes down the probability of occurrence
      of these k-mers at generation 1 and, consequently, increases the waiting time for
      apparition of these k-mers up to 40%. An analysis of existing TF binding sites
      unveils a significant proportion of k-mers exhibiting autocorrelation. Thus, our
      computations based on automata greatly improve the accuracy of predicting waiting
      times for the emergence of TF binding sites to appear during DNA evolution. We do
      the computation in the Bernoulli or M0 model; computations in the M1 model, a
      Markov model of order 1, are more costly in terms of time and memory but should
      produce similar results. While Behrens and Vingron considered specifically
      promoters of length 1000, we extend the results to promoters of any size; we
      exhibit the property that the probability that a k-mer occurs at generation time
      1 while being absent at time 0 behaves linearly with respect to the length of the
      promoter, which induces a hyperbolic behaviour of the waiting time of any k-mer
      with respect to the length of the promoter. The C code is available at
      www.lipn.univ-paris13.fr/~nicodeme/ .

PMID- 22468678
TI  - A topology-based score for pathway enrichment.
AB  - Investigators require intuitive tools to rationalize complex datasets generated
      by transcriptional profiling experiments. Pathway analysis methods, in which
      differentially expressed genes are mapped to databases of reference pathways to
      facilitate assessment of relative enrichment, lead investigators more effectively
      to biologically testable hypotheses. However, once a set of differentially
      expressed genes is isolated, pathway analysis approaches tend to ignore rich gene
      expression information and, moreover, do not exploit relationships between
      transcripts. In this article, we report the development of a new method in which
      both pathway topology and the magnitude of gene expression changes inform the
      scoring system, thereby providing a powerful filter in the enrichment of
      biologically relevant information. When four sample datasets were evaluated with
      this method, literature mining confirmed that those pathways germane to the
      physiological process under investigation were highlighted by our method relative
      to z-score overrepresentation calculations. Moreover, non-relevant processes were
      downgraded using the method described herein. The inclusion of expression and
      topological data in the calculation of a pathway regulation score (PRS)
      facilitated discrimination of key processes in real biological datasets.
      Specifically, by combining fold-change data for those transcripts exceeding a
      significance threshold, and by taking into account the potential for altered gene
      expression to impact upon downstream transcription, one may readily identify
      those pathways most relevant to pathophysiological processes.

PMID- 22468679
TI  - Using iterative ridge regression to explore associations between conditioned
      variables.
AB  - We address a specific case of joint probability mapping, where the information
      presented is the probabilistic associations of random variables under a certain
      condition variable (conditioned associations). Bayesian and dependency networks
      graphically map the joint probabilities of random variables, though both networks
      may identify associations that are independent of the condition (background
      associations). Since the background associations have the same topological
      features as conditioned associations, it is difficult to discriminate between
      conditioned and non-conditioned associations, which results in a major increase
      in the search space. We introduce a modification of the dependency network
      method, which produces a directed graph, containing only condition-related
      associations. The graph nodes represent the random variables and the graph edges
      represent the associations that arise under the condition variable. This method
      is based on ridge-regression, where one can utilize a numerically robust and
      computationally efficient algorithm implementation. We illustrate the method's
      efficiency in the context of a medically relevant process, the emergence of drug
      resistant variants of human immunodeficiency virus (HIV) in drug-treated, HIV
      infected people. Our mapping was used to discover associations between variants
      that are conditioned by the initiation of a particular drug treatment regimen. We
      have demonstrated that our method can recover known associations of such
      treatment with selected resistance mutations as well as documented associations
      between different mutations. Moreover, our method revealed novel associations
      that are statistically significant and biologically plausible.

PMID- 22468680
TI  - Accurate estimations of evolutionary times in the context of strong CpG
      hypermutability.
AB  - We consider the substitution model T92+CpG of DNA sequence evolution which takes
      into account the hypermutability of CpG dinucleotides, an effect that can be
      especially observed in vertebrate genomes. We provide an exact method to simulate
      the evolution of finite DNA sequences under this model and numerical procedures
      to infer evolutionary times in two cases: between an ancestral and a present
      sequence and between two homologous sequences. We show on simulated data that our
      new numerical method yields very accurate estimations of divergence times. In a
      context of strong CpG hypermutability, it clearly outperforms the classical
      estimation procedure that is solely based on the model T92 without CpG influence.
      Supplementary Material is available at www.liebertonline.com/cmb .

PMID- 22468681
TI  - Innate immune receptor expression in peri-implant tissues of patients with
      different susceptibility to periodontal diseases.
AB  - BACKGROUND: Although inflammation mediates the pathogenesis of periodontal
      diseases, the effects of innate immune responses on implant therapies have not
      been evaluated. Innate immune receptors, including toll-like-receptors (TLRs) and
      the receptor for advanced glycated end-products (RAGE), are upregulated within
      inflamed gingiva and are responsible for initiation of detrimental host
      responses. The aim of this study is to compare the expression of TLR2, TLR4, and
      RAGE in gingival tissues from participants susceptible to periodontitis and
      participants not susceptible to periodontitis before and after implant therapy.
      METHODS: Periodontally healthy participants received implant therapy for non
      periodontal edentulism. Participants susceptible to periodontitis were diagnosed
      with chronic periodontitis prior to implant therapy. Gingival biopsies were
      collected from edentulous ridges before implant installation and from peri
      implant mucosa 2 months after treatment. Histology, real-time PCR, and Western
      blot were used to evaluate levels of inflammatory infiltrate, TLR2, TLR4, and
      RAGE expression. RESULTS: Before implant therapy, elevated levels of RAGE were
      detected in gingival tissues from participants susceptible to periodontitis when
      compared to those from participants with healthy periodontiums, whereas no
      differences in the expression of TLR2 or TLR4 were detected. After implant
      therapy, there was an upregulation of RAGE and TLR4 levels that coincided with a
      downregulation of TLR2 levels in biopsies from participants susceptible to
      periodontitis. Levels of RAGE and TLR4 remained unchanged in biopsies from
      participants with healthy periodontiums, whereas TLR2 levels were significantly
      upregulated. Histologically, post-implant biopsies from participants susceptible
      to periodontitis displayed higher levels of inflammatory infiltrate. CONCLUSION:
      Elevated levels of inflammatory potential were found after implant therapy in
      participants susceptible to periodontitis.

PMID- 22468682
TI  - Periodontal status and hyperlipidemia: statin users versus non-users.
AB  - BACKGROUND: The association between serum lipids and periodontal disease has been
      studied predominantly in patients with chronic periodontitis with limited data
      available regarding periodontal status of patients with hyperlipidemia.
      Meanwhile, the impact of statins on the periodontal health of the population also
      remains largely underexplored. This study aims to assess the periodontal status
      among patients with hyperlipidemia and users of statins. METHODS: In this cross
      sectional study, 94 patients with hyperlipidemia (50 receiving statins and 44
      receiving non-pharmacologic therapy) and 46 control individuals who were
      normolipidemic underwent periodontal examination (plaque index, gingival index
      [GI], probing depth [PD], and clinical attachment level [CAL]). Biochemical
      parameters measured included serum triglyceride (TG), total cholesterol (TC), low
      density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol
      levels. RESULTS: PD and GI were significantly higher in patients with
      hyperlipidemia who were non-statin users compared with the normolipidemic
      individuals (P <0.001 [PD] and P <0.05 [GI]) and the statin group (P = 0.001 [PD]
      and P <0.05 [GI]). Periodontal parameters between statin users and the
      normolipidemic group did not differ significantly. After adjusting for
      confounders, positive and significant correlations were observed between PD and
      TG, and TC and LDL, whereas CAL shared correlation with TC and LDL. GI was
      correlated with TG and TC. Regression analyses revealed that whereas TC was
      associated significantly with PD (P <0.001), LDL showed significant association
      with CAL (P = 0.013). TG showed significant association with GI (P = 0.020).
      CONCLUSIONS: Our findings suggest that relative to the general population,
      patients with hyperlipidemia are more prone to periodontal disease. Also, within
      the limits of this study, statins have a positive impact on periodontal health.

PMID- 22468683
TI  - Coordination-driven self-assembly of 2D-metallamacrocycles using a new carbazole
      based dipyridyl donor: synthesis, characterization, and C60 binding study.
AB  - A new carbazole-based 90 degrees  dipyridyl donor 3,6-di(4
      pyridylethynyl)carbazole (L) containing carbazole-ethynyl functionality is
      synthesized in reasonable yield using the Sonagashira coupling reaction.
      Multinuclear NMR, electrospray ionization-mass spectrometry (ESI-MS), including
      single crystal X-ray diffraction analysis characterized this 90 degrees  building
      unit. The stoichiometry combination of L with several Pd(II)/Pt(II)-based 90
      degrees  acceptors (1a-1d) yielded [2 + 2] self-assembled metallacycles (2a-2d)
      under mild conditions in quantitative yields [1a = cis-(dppf)Pd(OTf)(2); 1b = cis
      (dppf)Pt(OTf)(2); 1c = cis-(tmen)Pd(NO(3))(2); 1d = 3,6-bis{trans
      Pt(C=C)(PEt(3))(2)(NO(3))}carbazole]. All these macrocycles were characterized by
      various spectroscopic techniques, and the molecular structure of 2a was
      unambiguously determined by single crystal X-ray diffraction analysis.
      Incorporation of ethynyl functionality to the carbazole backbone causes the
      resulted macrocycles (2a-2d) to be pi-electron rich and thereby exhibit strong
      emission characteristics. The macrocycle 2a has a large internal concave aromatic
      surface. The fluorescence quenching study suggests that 2a forms a ~1:1 complex
      with C(60) with a high association constant of K(sv) = 1.0 * 10(5) M(-1).

PMID- 22468685
TI  - Cardiovascular effects of Juniperus excelsa are mediated through multiple
      pathways.
AB  - Juniperus excelsa Bieb. is used in folk medicine for lowering blood pressure
      (BP). Its BP-lowering effect, endothelium-dependent and endothelium-independent
      vasodilator effects, and cardio-modulatory effect are reported here. The crude
      extract of J. excelsa (Je.Cr) which tested positive for the presence of
      anthraquinone, flavonoids, saponins, sterols, terpenes, and tannins induced a
      dose-dependent (10-300 mg/kg) fall in the arterial BP of anesthetized rats. In
      isolated rabbit aorta, Je.Cr (0.01-5.0 mg/mL) inhibited high K(+) (80 mM)- and
      phenylephrine (1 MUM)-induced contractions, like that caused by verapamil and
      papaverine. In endothelium-intact rat aortic preparations, N(omega)-nitro-l
      arginine methyl ester hydrochloride-sensitive vasodilator activity was noted from
      Je.Cr, which also relaxed the endothelium-denuded aorta tissues. In guinea pig
      atria, Je.Cr initially caused mild cardiac stimulation, followed by inhibition,
      like that exhibited by papaverine. Je.Cr prolonged the R-R interval in
      electrocardiogram of rats under anesthesia. These results reveal that
      cardiovascular effects of J. excelsa are mediated possibly through a combination
      of Ca(++) antagonism, nitric oxide-modulating mechanism, and phosphodiesterase
      inhibitory mechanism, which explain its medicinal use in hypertension.

PMID- 22468686
TI  - A novel aspartoacylase (ASPA) gene mutation in Canavan disease.
AB  - Canavan disease is a severe autosomal recessive leukodystrophy characterized by
      macrocephaly, ataxia, severe motor and mental retardation, dysmyelination, and
      progressive spongial atrophy of the brain. The human aspartoacylase (ASPA) gene,
      which catalyzes the deacetylation of N-acetyl-L-aspartate, is mutated in Canavan
      disease. In the presented family sequencing analysis for the aspartoacylase gene
      was performed on the blood samples of the parents as the affected child had died
      due to Canavan disease. After the mutation was detected, prenatal diagnosis was
      also performed and heterozygous Y88X mutation was detected in the fetus. In this
      report, we present a novel mutation Y88X within the aspartoacylase gene in a
      consanguineous family with an affected child diagnosed as Canavan disease.

PMID- 22468684
TI  - Design and synthesis of potent, orally efficacious hydroxyethylamine derived beta
      site amyloid precursor protein cleaving enzyme (BACE1) inhibitors.
AB  - We have previously shown that hydroxyethylamines can be potent inhibitors of the
      BACE1 enzyme and that the generation of BACE1 inhibitors with CYP 3A4 inhibitory
      activities in this scaffold affords compounds (e.g., 1) with sufficient
      bioavailability and pharmacokinetic profiles to reduce central amyloid-beta
      peptide (Abeta) levels in wild-type rats following oral dosing. In this article,
      we describe further modifications of the P1-phenyl ring of the hydroxyethylamine
      series to afford potent, dual BACE1/CYP 3A4 inhibitors which demonstrate improved
      penetration into the CNS. Several of these compounds caused robust reduction of
      Abeta levels in rat CSF and brain following oral dosing, and compound 37
      exhibited an improved cardiovascular safety profile relative to 1.

PMID- 22468687
TI  - Formation of high-capacity protein-adsorbing membranes through simple adsorption
      of poly(acrylic acid)-containing films at low pH.
AB  - Layer-by-layer polyelectrolyte adsorption is a simple, convenient method for
      introducing ion-exchange sites in porous membranes. This study demonstrates that
      adsorption of poly(acrylic acid) (PAA)-containing films at pH 3 rather than pH 5
      increases the protein-binding capacity of such polyelectrolyte-modified membranes
      3-6-fold. The low adsorption pH generates a high density of -COOH groups that
      function as either ion-exchange sites or points for covalent immobilization of
      metal-ion complexes that selectively bind tagged proteins. When functionalized
      with nitrilotriacetate (NTA)-Ni(2+) complexes, membranes containing
      PAA/polyethylenimine (PEI)/PAA films bind 93 mg of histidine(6)-tagged (His
      tagged) ubiquitin per cm(3) of membrane. Additionally these membranes isolate His
      tagged COP9 signalosome complex subunit 8 from cell extracts and show >90%
      recovery of His-tagged ubiquitin. Although modification with polyelectrolyte
      films occurs by simply passing polyelectrolyte solutions through the membrane for
      as little as 5 min, with low-pH deposition the protein binding capacities of such
      membranes are as high as for membranes modified with polymer brushes and 2-3-fold
      higher than for commercially available immobilized metal affinity chromatography
      (IMAC) resins. Moreover, the buffer permeabilities of polyelectrolyte-modified
      membranes that bind His-tagged protein are ~30% of the corresponding
      permeabilities of unmodified membranes, so protein capture can occur rapidly with
      low-pressure drops. Even at a solution linear velocity of 570 cm/h, membranes
      modified with PAA/PEI/PAA exhibit a lysozyme dynamic binding capacity (capacity
      at 10% breakthrough) of ~40 mg/cm(3). Preliminary studies suggest that these
      membranes are stable under depyrogenation conditions (1 M NaOH).

PMID- 22468688
TI  - Supportive family environments, genes that confer sensitivity, and allostatic
      load among rural African American emerging adults: a prospective analysis.
AB  - The purpose of this study was to investigate interactions between exposure to
      supportive family environments and genetic characteristics, which were
      hypothesized to forecast variations in allostatic load (AL) in a representative
      sample of 315 rural African American youths. Data on family environments were
      gathered when youths were 11-13, and genetic data were collected when they were
      16, years of age. Data on AL were obtained at the beginning of emerging
      adulthood, age 19 years. The data analyses revealed that, as predicted, emerging
      adults exposed to less supportive family environments across preadolescence
      manifested higher levels of AL when they carried the short (s) allele at the 5
      HTTLPR and an allele of DRD4 with seven or more repeats. This is an E(family
      environment) * G(5-HTTLPR status) * G(DRD4 status) interaction. These data
      suggest that African American youths carrying genes that confer sensitivity who
      are exposed to less supportive family environments may be at greater risk for
      adverse physical health consequences that AL presages.

PMID- 22468689
TI  - Reciprocal pathways between intimate partner violence and sleep in men and women.
AB  - Toward explicating associations and directionality of effects between
      relationship processes and a fundamental facet of health, we examined cross
      sectional and longitudinal associations between the perpetration of intimate
      partner violence (IPV) and men and women's sleep. During two assessments, a
      diverse community sample of couples reported on their perpetrated acts of
      psychological and physical IPV and their sleep quality. Cross-sectional
      associations between IPV and sleep were evident for both partners, in particular
      between psychological IPV and sleep. A dyadic path analysis controlling for the
      autoregressive effects and within-time correlations revealed longitudinal links
      between men's perpetration of IPV and their sleep quality. Even though high
      levels of stability in all IPV and sleep measures were observed over time,
      results indicated that sleep problems predicted increases in the perpetration of
      psychological IPV over time for both men and women. Cross-partner effects emerged
      for men, revealing that men's sleep problems were strongly affected by their
      partner's earlier perpetration of IPV and sleep difficulties. Findings illustrate
      the significance of contemporaneous, dyadic assessments of relationship processes
      and sleep for a better understanding of both facets of adaptation, and have
      implications for those wishing to understand the etiology and consequences of the
      perpetration of IPV for both men and women.

PMID- 22468690
TI  - Maternal age, investment, and parent-child conflict: a mediational test of the
      terminal investment hypothesis.
AB  - Drawing on the evolutionary terminal investment hypothesis and Trivers' (1974)
      parent-offspring conflict theory, we advance and evaluate a mediational model
      specifying why and how maternal age, via mating effort and parental investment,
      affects mother-child conflict. Data from a longitudinal study of 757 families
      indicate that (a) older maternal age predicts lower mating effort during the
      child's first 5 years of life, and (b) thereby, higher maternal investment in
      middle childhood when the child is around 10 years old. (c) Higher maternal
      investment, in turn, forecasts less child-perceived mother-child conflict in
      adolescence (age 15). These results proved robust against theoretically relevant
      covariates (family resources, parity, maternal education, and maternal
      personality characteristics) and in the context of an autoregressive model. Study
      limitations are noted and results are discussed in terms of the unique
      contributions of an evolutionary perspective to the determinants-of-parenting
      literature.

PMID- 22468691
TI  - Father involvement, paternal sensitivity, and father-child attachment security in
      the first 3 years.
AB  - To reach a greater understanding of the early father-child attachment
      relationship, this study examined concurrent and longitudinal associations among
      father involvement, paternal sensitivity, and father-child attachment security at
      13 months and 3 years of age. Analyses revealed few associations among these
      variables at 13 months of age, but involvement and sensitivity independently
      predicted father-child attachment security at age 3. Moreover, sensitivity
      moderated the association between involvement and attachment security at 3 years.
      Specifically, involvement was unrelated to attachment security when fathers were
      highly sensitive, but positively related to attachment security when fathers were
      relatively less sensitive. Father involvement was also moderately stable across
      the two time points, but paternal sensitivity was not. Furthermore, there was
      significant stability in father-child attachment security from 13 months to 3
      years. Secure attachment at 13 months also predicted greater levels of paternal
      sensitivity at 3 years, with sensitivity at age 3 mediating the association
      between 13 month and 3 year attachment security. In sum, a secure father-child
      attachment relationship (a) was related to both quantity and quality of fathering
      behavior, (b) remained relatively stable across early childhood, and (c)
      predicted increased paternal sensitivity over time. These findings further our
      understanding of the correlates of early father-child attachment, and underscore
      the need to consider multiple domains of fathers' parenting and reciprocal
      relations between fathering behavior and father-child attachment security.

PMID- 22468692
TI  - Identification and expression of small non-coding RNA, L10-Leader, in different
      growth phases of Streptococcus mutans.
AB  - Streptococcus mutans is one of the major cariogenic bacteria in the oral
      environment. Small non-coding RNAs (sRNAs) play important roles in the regulation
      of bacterial growth, stress tolerance, and virulence. In this study, we
      experimentally verified the existence of sRNA, L10-Leader, in S. mutans for the
      first time. Our results show that the expression level of L10-Leader was growth
      phase dependent in S. mutans and varied among different clinical strains of S.
      mutans. The level of L10-Leader in S. mutans UA159 was closely related to the pH
      value, but not to the concentrations of glucose and sucrose in culture medium. We
      predicted target mRNAs of L10-Leader bioinformatically and found that some of
      these mRNAs were related to growth and stress response. Five predicted mRNA
      targets were selected and detected by quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR), and we found that the expression levels of
      these mRNAs were closely related to the level of L10-Leader at different growth
      phases of the bacteria. Our results indicate that L10-Leader may play an
      important role in the regulation of responses in S. mutans, especially during its
      growth phase and acid adaption response.

PMID- 22468693
TI  - Phytochemical analysis of Gymnema sylvestre and evaluation of its antimicrobial
      activity.
AB  - Gymnema sylvestre (CS 149), known to be a rich source of saponins and other
      valuable phytochemicals, has been analysed for antimicrobial activity. The
      chloroform extracts of aerial and root parts of G. sylvestre exhibited higher
      antimicrobial activity as compared to diethyl ether and acetone. The root
      extracts of chloroform have shown competitive minimum inhibitory concentration
      and minimum bactericidal concentration values in the range of 0.04-1.28 mg mL(-1)
      and 0.08-2.56 mg/mL, respectively, towards the pathogens. The GC-MS analysis of
      chloroform extracts has shown the presence of compounds like eicosane, oleic
      acid, stigmasterol and vitamin E.

PMID- 22468694
TI  - The electrocardiographic early repolarization pattern in athletes: normal variant
      or sudden death risk factor?
AB  - The clinical evaluation of athletes during symptom evaluation or pre
      participation screening often involves interpretation of the 12-lead
      electrocardiogram (ECG). Differentiating abnormal ECG findings suggestive of
      underlying cardiovascular disease from benign findings caused by exercise-induced
      cardiac adaptations can be challenging, and recent clinical guidelines have been
      created for this purpose. One of the most common ECG findings in athletes is the
      early repolarization pattern (ERP), characterized by diffuse J-point elevation
      and concave ST-segment elevation, and long regarded as a normal variant. However,
      recently published data suggest that the ERP may be a marker of increased risk
      for sudden cardiac death (SCD) in the general population. The observation that
      the ERP can indicate increased SCD risk has important implications for the
      clinician charged with the care of athletes. This review will describe the
      evolving understanding of the ERP and will explore the relevance of the ERP for
      the care of athletes.

PMID- 22468695
TI  - Oxidative stress increases continuously with BMI and age with unfavourable
      profiles in males.
AB  - Oxidative stress is a risk factor for chronic diseases and was previously shown
      to be independently associated with obesity. The authors investigated the
      relationship between body mass index (BMI), age and oxidative stress on 2190
      subjects undergoing a health care examination. Total antioxidant status (TAS),
      total peroxides (TOC) and autoantibodies against oxidized LDL (oLAb) were used as
      oxidative stress biomarkers in addition to serum lipoproteins, bilirubin and uric
      acid. Gender-specific differences were observed for age, BMI, serum
      concentrations of bilirubin, low-density lipoprotein (LDL), uric acid and TAS,
      all of which were higher in males (p < 0.001), while high-density lipoprotein
      (HDL), HDL/LDL ratio and TOC were higher in females (p < 0.001). Total
      cholesterol (p < 0.05) and LDL were increased (p < 0.05), while HDL was decreased
      (p < 0.05) in overweight and obese subjects. This was accompanied by increased
      uric acid and TAS concentrations. Lowest oLAb titers were detected in obese
      subjects. In extremely obese subjects, increased TOC and decreased TAS were
      observed in spite of high uric acid levels. These results demonstrate that
      oxidative stress increases with increasing BMI and age, as a sequel to an
      impaired antioxidant status, the consumption of oLAbs, an increase of peroxides
      and uric acid and a disadvantaged lipid profile.

PMID- 22468696
TI  - Natural and biomimetic materials for the detection of insulin.
AB  - Microgravimetric sensors have been developed for detection of insulin by using
      quartz crystal microbalances as transducers, in combination with sensitive
      layers. Natural antibodies as coatings were compared with biomimetic materials to
      fabricate mass-sensitive sensors. For this purpose polyurethane was surface
      imprinted by insulin, which acts as a synthetic receptor for reversible analyte
      inclusion. The sensor responses for insulin give a pronounced concentration
      dependence, with a detection limit down to 1 MUg/mL and below. Selectivity
      studies reveal that these structured polymers lead to differentiation between
      insulin and glargine. Moreover, antibody replicae were generated by a double
      imprinting process. Thus, biological recognition capabilities of immunoglobulins
      are transferred to synthetic polymers. In the first step, natural-immunoglobulin
      imprinted nanoparticles were synthesized. Subsequently, these templated particles
      were utilized for creating positive images of natural antibodies on polymer
      layers. These synthetic coatings, which are more robust than natural analogues,
      can be produced in large amount. These biomimetic sensors are useful in the
      biotechnology of insulin monitoring.

PMID- 22468697
TI  - Validity and reproducibility of the asthma core International Study of Asthma and
      Allergies in Childhood (ISAAC) written questionnaire obtained by telephone
      survey.
AB  - OBJECTIVE: To assess the reproducibility and validity of the International Study
      of Asthma and Allergies in Childhood (ISAAC) asthma written questionnaire (IAWQ)
      for 6- to 7-year-old children administered to their parents/caregivers through a
      telephone interview. METHODS: Our study included 100 children selected from three
      health units in Rio de Janeiro, Brazil. In total, 50 asthmatic and 50 non
      asthmatic children were evaluated; all participants were required to own a
      household telephone line. Initially, telephone interviews were conducted with the
      parents/caregivers using the IAWQ. After 2 weeks, parents/caregivers were invited
      to complete the IAWQ under supervision provided by the researchers. After fifteen
      days, the telephone interviews were repeated. The reproducibility between the two
      telephone interviews was assessed using kappa (kappa) coefficients; the construct
      validity was assessed by comparing the answers obtained in the initial telephone
      interview in both groups according to the clinical diagnosis of asthma performed
      by a specialist using sensitivity and specificity coefficients. RESULTS: Overall,
      data from 75 children (39 asthmatics) were analyzed, as 25 patients were excluded
      from the study (11 did not answer phone calls and the responding
      parents/caregivers for 14 patients were not the same in all study phases).
      Perfect agreement was observed for the indicator "wheezing in the last 12 months"
      (kappa = 1), while substantial agreement was observed for the "wheezing with
      exercise," "speech limited by wheezing," and "asthma ever" indicators (kappa
      range, 0.7-0.8). The sensitivity and specificity for "wheezing within the last 12
      months" were 64.1% (95% confidence interval (CI), 47.2-78.8) and 88.9% (95% CI,
      73.9-96.9), respectively. For the "asthma ever" indicator, the sensitivity and
      specificity were 87.2% (95% CI, 77.6-95.7) and 100% (95% CI, 90.3-1),
      respectively. Questionnaire specificity was high for all asthma severity
      indicators. CONCLUSIONS: The IAWQ for children aged 6-7 years adapted for
      telephone interviews showed good reproducibility and adequate validity with an
      ability to distinguish between asthmatic and non-asthmatic participants. Thus,
      this method could be utilized in epidemiological studies on childhood asthma in
      locations where telephone lines are available.

PMID- 22468698
TI  - Hollow iron oxide nanoparticles for application in lithium ion batteries.
AB  - Material design in terms of their morphologies other than solid nanoparticles can
      lead to more advanced properties. At the example of iron oxide, we explored the
      electrochemical properties of hollow nanoparticles with an application as a
      cathode and anode. Such nanoparticles contain very high concentration of cation
      vacancies that can be efficiently utilized for reversible Li ion intercalation
      without structural change. Cycling in high voltage range results in high capacity
      (~132 mAh/g at 2.5 V), 99.7% Coulombic efficiency, superior rate performance (133
      mAh/g at 3000 mA/g) and excellent stability (no fading at fast rate during more
      than 500 cycles). Cation vacancies in hollow iron oxide nanoparticles are also
      found to be responsible for the enhanced capacity in the conversion reactions. We
      monitored in situ structural transformation of hollow iron oxide nanoparticles by
      synchrotron X-ray absorption and diffraction techniques that provided us clear
      understanding of the lithium intercalation processes during electrochemical
      cycling.

PMID- 22468699
TI  - Carbon monoxide-assisted synthesis of single-crystalline Pd tetrapod nanocrystals
      through hydride formation.
AB  - Carbon monoxide can adsorb specifically on Pd(111) to induce the formation of
      unique Pd nanostructures. In the copresence of CO and H(2), single-crystalline Pd
      tetrapod nanocrystals have now been successfully prepared. The Pd tetrapods are
      enclosed by (111) surfaces and are yielded through hydride formation. Density
      functional theory calculations revealed that the formation of PdH(x) in the
      presence of H(2) reduces the binding energy of CO on Pd and thus helps to
      decrease the CO coverage during the synthesis, which is essential to the
      formation of the PdH(x) tetrapod nanocrystals. In addition to tetrapod
      nanocrystals, tetrahedral nanocrystals were also produced in the copresence of CO
      and H(2) when the reaction temperature was ramped to further lower the CO
      coverage. Upon aging in air, the as-prepared PdH(x) nanocrystals exhibited a
      shape-dependent hydrogen releasing behavior. The conversion rate of PdH(x)
      tetrapod nanocrystals into metallic Pd was faster than that of tetrahedral
      nanocrystals.

PMID- 22468700
TI  - Novel models for assessing blood-brain barrier drug permeation.
AB  - INTRODUCTION: The blood-brain barrier (BBB) is a selectively permeable micro
      vascular unit which prevents many central nervous system (CNS)-targeted compounds
      from reaching the brain. A significant problem in CNS drug development is the
      ability to model BBB permeability in a timely, reproducible and cost-effective
      manner. Through the years, several models have been used such as artificial
      membranes, cell culture and animal models. AREAS COVERED: In this focused review,
      the authors cover novel models which have been developed or are in the process of
      being developed which can be used in modeling BBB. These models can either be
      used to determine BBB permeability or whether a compound may be disrupting the
      BBB. Many of these models lend themselves to high-throughput screening. The main
      model organisms covered here are the grasshopper (Locusta migratoria), fruit fly
      (Drosophila melanogaster) and zebrafish (Danio rerio). EXPERT OPINION: Many of
      the models covered here have only recently been utilized for BBB studies and
      still needs to be fully studied for its impact on reducing costs during drug
      development. The strength of these models lay in the fact that a whole organism
      experiment can be done in high throughput fashion as compared with classical
      vertebrate models such as micro-dialysis.

PMID- 22468701
TI  - Investigation of the effects of head irradiation with gamma rays and protons on
      startle and pre-pulse inhibition behavior in mice.
AB  - With the increased international emphasis on manned space exploration, there is a
      growing need to understand the impact of the spaceflight environment on health
      and behavior. One particularly important aspect of this environment is low-dose
      radiation. In the present studies, we first characterized the gamma- and proton
      irradiation dose effect on acoustic startle and pre-pulse inhibition behaviors in
      mice exposed to 0-5 Gy brain-localized irradiation, and assessed these effects 2
      days later. Subsequently, we used 2 Gy to assess the time course of gamma- and
      proton-radiation effects on startle reactivity 0-8 days after exposure. Exposures
      targeted the brain to minimize the impact of peripheral inflammation-induced
      sickness behavior. The effects of radiation on startle were subtle and acute.
      Radiation reduced the startle response at 2 and 5 Gy. Following a 2-Gy exposure,
      the response reached a minimum at the 2-day point. Proton and gamma-ray exposures
      did not differ in their impact on startle. We found there were no effects of
      radiation on pre-pulse inhibition of the startle response.

PMID- 22468702
TI  - Animal models and medical countermeasures development for radiation-induced lung
      damage: report from an NIAID Workshop.
AB  - Since 9/11, there have been concerns that terrorists may detonate a radiological
      or nuclear device in an American city. Aside from several decorporation and
      blocking agents for use against internal radionuclide contamination, there are
      currently no medications within the Strategic National Stockpile that are
      approved to treat the immediate or delayed complications resulting from
      accidental exposure to radiation. Although the majority of research attention has
      focused on developing countermeasures that target the bone marrow and
      gastrointestinal tract, since they represent the most acutely radiosensitive
      organs, individuals who survive early radiation syndromes will likely suffer late
      effects in the months that follow. Of particular concern are the delayed effects
      seen in the lung that play a major role in late mortality seen in radiation
      exposed patients and accident victims. To address these concerns, the National
      Institute of Allergy and Infectious Diseases convened a workshop to discuss
      pulmonary model development, mechanisms of radiation-induced lung injury, targets
      for medical countermeasures development, and end points to evaluate treatment
      efficacy. Other topics covered included guidance on the challenges of developing
      and licensing drugs and treatments specific to a radiation lung damage
      indication. This report reviews the data presented, as well as key points from
      the ensuing discussion.

PMID- 22468703
TI  - In vitro evaluation of combined temozolomide and radiotherapy using X  rays and
      high-linear energy transfer radiation for glioblastoma.
AB  - High-linear energy transfer radiation offers superior biophysical properties over
      conventional radiotherapy and may have a great potential for treating
      radioresistant tumors, such as glioblastoma. However, very little pre-clinical
      data exists on the effects of high-LET radiation on glioblastoma cell lines and
      on the concomitant application of chemotherapy. This study investigates the in
      vitro effects of temozolomide in combination with low-energy protons and alpha
      particles. Cell survival, DNA damage and repair, and cell growth were examined in
      four human glioblastoma cell lines (LN18, T98G, U87 and U373) after treatment
      with either X rays, protons (LET 12.91 keV/MUm), or alpha particles (LET 99.26
      keV/MUm) with or without concurrent temozolomide at clinically-relevant doses of
      25 and 50 MUM. The relative biological effectiveness at 10% survival (RBE(10))
      increased as LET increased: 1.17 and 1.06 for protons, and 1.84 and 1.68 for
      alpha particles in the LN18 and U87 cell lines, respectively. Temozolomide
      administration increased cell killing in the O(6)-methylguanine DNA
      methyltransferase-methylated U87 and U373 cell lines. In contrast, temozolomide
      provided no therapeutic enhancement in the methylguanine DNA methyltransferase
      unmethylated LN18 and T98G cell lines. In addition, the residual number of gamma
      H2AX foci at 24 h after treatment with radiation and concomitant temozolomide was
      found to be lower than or equal to that expected by DNA damage with either of the
      individual treatments. Kinetics of foci disappearance after X-ray and proton
      irradiation followed similar time courses; whereas, loss of gamma-H2AX foci after
      alpha particle irradiation occurred at a slower rate than that by low-LET
      radiation (half-life 12.51-16.87 h). The combination of temozolomide with
      different radiation types causes additive rather than synergistic cytotoxicity.
      Nevertheless, particle therapy combined with chemotherapy may offer a promising
      alternative with the additional benefit of superior biophysical properties. It is
      also possible that new fractionation schedules could be designed to exploit the
      change in DNA repair kinetics when MGMT-methylated cells respond to high-LET
      radiation.

PMID- 22468704
TI  - Development and licensure of medical countermeasures to treat lung damage
      resulting from a radiological or nuclear incident.
AB  - Due to the ever-present threat of a radiological or nuclear accident or attack,
      the National Institute of Allergy and Infectious Diseases, Radiation Medical
      Countermeasures Program was initiated in 2004. Since that time, the Program has
      funded research to establish small and large animal models for radiation damage,
      as well as the development of approaches to mitigate/treat normal tissue damage
      following radiation exposure. Because some of these exposures may be high-dose,
      and yet heterogeneous, the expectation is that some victims will survive initial
      acute radiation syndromes (e.g. hematopoietic and gastrointestinal), but then
      suffer from potentially lethal lung complications. For this reason, efforts have
      concentrated on the development of animal models of lung irradiation damage that
      mimic expected exposure scenarios, as well as drugs to treat radiation-induced
      late lung sequelae including pneumonitis and fibrosis. Approaches targeting
      several pathways are under study, with the eventual goal of licensure by the
      United States Food and Drug Administration for government stockpiling. This
      Commentary outlines the status of countermeasure development in this area and
      provides information on the specifics of licensure requirements, as well as
      guidance and a discussion of challenges involved in developing and licensing
      drugs and treatments specific to a radiation lung damage indication.

PMID- 22468705
TI  - Efficacy of radiation countermeasures depends on radiation quality.
AB  - The detonation of a nuclear weapon or a nuclear accident represent possible
      events with significant exposure to mixed neutron/gamma-radiation fields.
      Although radiation countermeasures generally have been studied in subjects
      exposed to pure photons (gamma or X rays), the mechanisms of injury of these low
      linear energy transfer (LET) radiations are different from those of high-LET
      radiation such as neutrons, and these differences may affect countermeasure
      efficacy. We compared 30-day survival in mice after varying doses of pure gamma
      and mixed neutron/gamma (mixed field) radiation (MF, Dn/Dt = 0.65), and also
      examined peripheral blood cells, bone marrow cell reconstitution, and cytokine
      expression. Mixed-field-irradiated mice displayed prolonged defects in T-cell
      populations compared to mice irradiated with pure gamma photons. In mouse
      survival assays, the growth factor granulocyte colony-stimulating factor (G-CSF)
      was effective as a (post-irradiation) mitigator against both gamma-photons and
      mixed-field radiation, while the thrombopoietin (TPO) mimetic ALXN4100TPO was
      effective only against gamma irradiation. The results indicate that radiation
      countermeasures should be tested against radiation qualities appropriate for
      specific scenarios before inclusion in response plans.

PMID- 22468707
TI  - Structural alignment of RNA with triple helix structure.
AB  - Structural alignment is useful in identifying members of ncRNAs. Existing tools
      are all based on the secondary structures of the molecules. There is evidence
      showing that tertiary interactions (the interaction between a single-stranded
      nucleotide and a base-pair) in triple helix structures are critical in some
      functions of ncRNAs. In this article, we address the problem of structural
      alignment of RNAs with the triple helix. We provide a formal definition to
      capture a simplified model of a triple helix structure, then develop an algorithm
      of O(mn(3)) time to align a query sequence (of length m) with known triple helix
      structure with a target sequence (of length n) with an unknown structure. The
      resulting algorithm is shown to be useful in identifying ncRNA members in a
      simulated genome.

PMID- 22468706
TI  - No threshold for the induction of chromosomal damage at clinically relevant low
      doses of X rays.
AB  - The recent steep increase in population dose from radiation-based medical
      diagnostics, such as computed tomography (CT) scans, requires insight into human
      health risks, especially in terms of cancer development. Since the induction of
      genetic damage is considered a prominent cause underlying the carcinogenic
      potential of ionizing radiation, we quantified the induction of micronuclei and
      loss of heterozygosity events in human cells after exposure to clinically
      relevant low doses of X rays. A linear dose-response relationship for induction
      of micronuclei was observed in human fibroblasts with significantly increased
      frequencies at doses as low as 20 mGy. Strikingly, cells exposed during S-phase
      displayed the highest induction, whereas non S-phase cells showed no significant
      induction below 100 mGy. Similarly, the induction of loss of heterozygosity in
      human lymphoblastoid cells quantified at HLA loci, was linear with dose and
      reached significance at 50 mGy. Together the findings favor a linear-no-threshold
      model for genetic damage induced by acute exposure to ionizing radiation. We
      speculate that the higher radiosensitivity of S-phase cells might relate to the
      excessive cancer risk observed in highly proliferative tissues in radiation
      exposed organisms.

PMID- 22468708
TI  - The k partition-distance problem.
AB  - Many applications of data partitioning (clustering) have been well studied in
      bioinformatics. Consider, for instance, a set N of organisms (elements) based on
      DNA marker data. A partition divides all elements in N into two or more disjoint
      clusters that cover all elements, where a cluster contains a non-empty subset of
      N. Different partitioning algorithms may produce different partitions. To compute
      the distance and find the consensus partition (also called consensus clustering)
      between two or more partitions are important and interesting problems that arise
      frequently in bioinformatics and data mining, in which different distance
      functions may be considered in different partition algorithms. In this article,
      we discuss the k partition-distance problem. Given a set of elements N with k
      partitions of N, the k partition-distance problem is to delete the minimum number
      of elements from each partition such that all remaining partitions become
      identical. This problem is NP-complete for general k > 2 partitions, and no
      algorithms are known at present. We design the first known heuristic and
      approximation algorithms with performance ratios 2 to solve the k partition
      distance problem in O(k . rho . |N|) time, where rho is the maximum number of
      clusters of these k partitions and |N| is the number of elements in N. We also
      present the first known exact algorithm in O(l . 2(l).k(2) . |N|(2)) time, where
      l is the partition-distance of the optimal solution for this problem.
      Performances of our exact and approximation algorithms in testing the random data
      with actual sets of organisms based on DNA markers are compared and discussed.
      Experimental results reveal that our algorithms can improve the computational
      speed of the exact algorithm for the two partition-distance problem in practice
      if the maximum number of elements per cluster is less than rho. From both
      theoretical and computational points of view, our solutions are at most twice the
      partition-distance of the optimal solution. A website offering the interactive
      service of solving the k partition-distance problem using our and previous
      algorithms is available (see http://mail.tmue.edu.tw/~yhchen/KPDP.html).

PMID- 22468709
TI  - Algorithm for haplotype inference via galled-tree networks with simple galls.
AB  - The problem of determining haplotypes from genotypes has gained considerable
      prominence in the research community. Here the focus is on determining sets of
      SNP values on individual chromosomes since such information captures the genetic
      causes of diseases. The most efficient algorithmic tool for haplotyping is based
      on perfect phylogenetic trees. A drawback of this method is that it cannot be
      applied in situations when the data contains homoplasies (multiple mutations of
      the same character) or recombinations. Recently, Song et al. ( 2005 ) studied the
      two cases: haplotyping via imperfect phylogenies with a single homoplasy and via
      galled-tree networks with one gall. In Gupta et al. ( 2010 ), we have shown that
      the haplotyping via galled-tree networks is NP-hard, even if we restrict to the
      case when every gall contains at most 3 mutations. We present a polynomial
      algorithm for haplotyping via galled-tree networks with simple galls (each having
      two mutations) for genotype matrices which satisfy a natural condition which is
      implied by presence of at least one 1 in each column that contains a 2. In the
      end, we give the experimental results comparing our algorithm with PHASE on
      simulated data.

PMID- 22468710
TI  - A systematic review of research undertaken in vocational rehabilitation for
      people with multiple sclerosis.
AB  - OBJECTIVE: The National Service Framework (NSF) for Long-Term Neurological
      Conditions (LTNC) highlights the need for vocational rehabilitation (VR) services
      in quality requirement 6. As a part of a review of this requirement, an extensive
      literature review was undertaken to identify, review and report on all relevant
      research undertaken in the area of employment for people with multiple sclerosis
      (MS). DATA SOURCES: A systematic review of the English language literature for
      studies under the headings: multiple sclerosis and employment, unemployment,
      vocational rehabilitation, occupational health, job and work adjustment. The
      following databases were systematically searched AMED (1985 to Feb 2010), CINAHL
      (1982 to Feb 2010), PsycINFO (1806 to Feb 2010), EMBASE (1974 to Feb 2010),
      Medline (1950 to Feb 2010) and PubMed (1950 to Feb 2010). DATA EXTRACTION AND
      STUDY SELECTION: Four hundred and sixty-two papers were identified. This number
      was reduced removing the duplicates, non-English, not reporting research, not
      primarily about MS and not primarily about work which left 89 papers reviewed.
      CONCLUSION: The body of evidence reviewed gives clear indicators as to what the
      barriers to working with MS are and what is required for a VR service to meet the
      often complex needs of people with MS. Further research is needed to identify the
      efficacy of different models of VR, and their cost-effectiveness, and
      particularly for means of identifying and measuring the effectiveness of
      interventions that support work retention.

PMID- 22468711
TI  - Phthalocyanine-peptide conjugates for epidermal growth factor receptor targeting.
AB  - Four phthalocyanine (Pc)-peptide conjugates designed to target the epidermal
      growth factor receptor (EGFR) were synthesized and evaluated in vitro using four
      cell lines: human carcinoma A431 and HEp2, human colorectal HT-29, and kidney
      Vero (negative control) cells. Two peptide ligands for EGFR were investigated:
      EGFR-L1 and -L2, bearing 6 and 13 amino acid residues, respectively. The peptides
      and Pc-conjugates were shown to bind to EGFR using both theoretical (Autodock)
      and experimental (SPR) investigations. The Pc-EGFR-L1 conjugates 5a and 5b
      efficiently targeted EGFR and were internalized, in part due to their cationic
      charge, whereas the uncharged Pc-EGFR-L2 conjugates 4b and 6a poorly targeted
      EGFR maybe due to their low aqueous solubility. All conjugates were nontoxic
      (IC(50) > 100 MUM) to HT-29 cells, both in the dark and upon light activation (1
      J/cm(2)). Intravenous (iv) administration of conjugate 5b into nude mice bearing
      A431 and HT-29 human tumor xenografts resulted in a near-IR fluorescence signal
      at ca. 700 nm, 24 h after administration. Our studies show that Pc-EGFR-L1
      conjugates are promising near-IR fluorescent contrast agents for CRC and
      potentially other EGFR overexpressing cancers.

PMID- 22468712
TI  - Proteomic screen identifies IGFBP7 as a novel component of endothelial cell
      specific Weibel-Palade bodies.
AB  - Vascular endothelial cells contain unique storage organelles, designated Weibel
      Palade bodies (WPBs), that deliver inflammatory and hemostatic mediators to the
      vascular lumen in response to agonists like thrombin and vasopressin. The main
      component of WPBs is von Willebrand factor (VWF), a multimeric glycoprotein
      crucial for platelet plug formation. In addition to VWF, several other components
      are known to be stored in WPBs, like osteoprotegerin, monocyte chemoattractant
      protein-1 and angiopoetin-2 (Ang-2). Here, we used an unbiased proteomics
      approach to identify additional residents of WPBs. Mass spectrometry analysis of
      purified WPBs revealed the presence of several known components such as VWF, Ang
      2, and P-selectin. Thirty-five novel candidate WPB residents were identified that
      included insulin-like growth factor binding protein-7 (IGFBP7), which has been
      proposed to regulate angiogenesis. Immunocytochemistry revealed that IGFBP7 is a
      bona fide WPB component. Cotransfection studies showed that IGFBP7 trafficked to
      pseudo-WPB in HEK293 cells. Using a series of deletion variants of VWF, we showed
      that targeting of IGFBP7 to pseudo-WPBs was dependent on the carboxy-terminal D4
      C1-C2-C3-CK domains of VWF. IGFBP7 remained attached to ultralarge VWF strings
      released upon exocytosis of WPBs under flow. The presence of IGFBP7 in WPBs
      highlights the role of this subcellular compartment in regulation of
      angiogenesis.

PMID- 22468713
TI  - Synthesis of C3' modified nucleosides for selective generation of the C3'-deoxy
      3'-thymidinyl radical: a proposed intermediate in LEE induced DNA damage.
AB  - DNA damage pathways induced by low-energy electrons (LEEs) are believed to
      involve the formation of 2-deoxyribose radicals. These radicals, formed at the
      C3' and C5' positions of nucleotides, are the result of cleavage of the C-O
      phosphodiester bond through transfer of LEEs to the phosphate group of DNA
      oligomers from the nucleobases. A considerable amount of information has been
      obtained to illuminate the identity of the unmodified oligonucleotide products
      formed through this process. There exists, however, a paucity of information as
      to the nature of the modified lesions formed from degradation of these sugar
      radicals. To determine the identity of the damage products formed via the 2',3'
      dideoxy-C3'-thymidinyl radical (C3'(dephos) sugar radical), phenyl selenide and
      acyl modified sugar and nucleoside derivatives have been synthesized, and their
      suitability as photochemical precursors of the radical of interest has been
      evaluated. Upon photochemical activation of C3'-derivatized nucleosides in the
      presence of the hydrogen atom donor tributyltin hydride, 2',3'-dideoxythymidine
      is formed indicating the selective generation of the C3'(dephos) sugar radical.
      These precursors will make the identification and quantification of products of
      DNA damage derived from radicals generated by LEEs possible.

PMID- 22468714
TI  - Short message service reduces dropout in childhood obesity treatment: a
      randomized controlled trial.
AB  - OBJECTIVE: Lifestyle programs can reduce the level of overweight in children;
      however, maintenance results and adherence to treatment are difficult to achieve.
      New technologies, such as the Short Message Service (SMS), might be a promising
      tool for enhancing interventions. The effect of an SMS approach aimed at
      improving treatment results and reducing dropout rates in a pediatric lifestyle
      intervention, is explored. METHOD: Overweight and obese children (N = 141; age 7
      12 years) participating in a lifestyle program were randomly assigned to an
      intervention group receiving an SMS Maintenance Treatment (SMSMT) for 38 weeks (n
      = 73) or to a control group receiving no SMSMT (n = 68). Children were asked to
      send weekly self-monitoring data on exercise, eating behavior, and emotional well
      being. In return, they received tailored feedback messages. A differential
      decrease in BMI was analyzed with repeated measures ANOVA and dropout with
      logistic regression analysis. RESULTS: We found no significant difference in BMI
      decrease between the two groups after 12 months; however, we showed that the
      SMSMT group had 3.25 times less probability of dropping out after 1 year (p =
      .01) than controls. In the first 3 months of SMSMT, the SMSMT completers sent
      0.80 SMSs per week, which reduced to 0.50 SMSs in the final 3 months. Younger
      children sent more SMSs (p = .03). CONCLUSIONS: These results indicate that SMSMT
      is effective in reducing dropout rates from a pediatric lifestyle intervention.
      Future research should examine the effectiveness of SMSMT on weight management
      and related psychosocial variables.

PMID- 22468715
TI  - An evaluation of The Great Escape: can an interactive computer game improve young
      children's fire safety knowledge and behaviors?
AB  - OBJECTIVE: Fire is a leading cause of unintentional injury and, although young
      children are at particularly increased risk, there are very few evidence-based
      resources available to teach them fire safety knowledge and behaviors. Using a
      pre-post randomized design, the current study evaluated the effectiveness of a
      computer game (The Great Escape) for teaching fire safety information to young
      children (3.5-6 years). METHOD: Using behavioral enactment procedures, children's
      knowledge and behaviors related to fire safety were compared to a control group
      of children before and after receiving the intervention. RESULTS: The results
      indicated significant improvements in knowledge and fire safety behaviors in the
      intervention group but not the control. CONCLUSION: Using computer games can be
      an effective way to promote young children's understanding of safety and how to
      react in different hazardous situations.

PMID- 22468716
TI  - Randomized controlled trial of collaborative implementation intentions targeting
      working adults' physical activity.
AB  - OBJECTIVE: The research tested the efficacy of planning and partner-based
      interventions to promote physical activity over six months. METHOD: Local
      government (council) employees (N = 257) were randomly allocated to one of four
      conditions (collaborative implementation intentions; partner-only; implementation
      intentions; control group) before completing measures at baseline and follow-ups
      at 1, 3 and 6 months. Outcome measures comprised validated self-report measures
      of physical activity: the international physical activity questionnaire (IPAQ;
      Craig et al., 2003) and self-report walking and exercise tables (SWET; Prestwich
      et al., 2012); psychosocial mediators (enjoyment, intention, self-efficacy,
      social influence); weight and waist size (baseline and 6 months only). RESULTS:
      As well as losing the most weight, there was evidence that participants in the
      collaborative implementation-intention group were more physically active than
      each of the other three groups at 1-, 3- and 6-month follow-ups. Those in the
      implementation-intention and partner-only conditions did not outperform the
      control group on most measures. CONCLUSION: Collaborative implementation
      intentions represent a potentially useful intervention to change important health
      behaviors that help reduce weight.

PMID- 22468717
TI  - Aptamer-functionalized hydrogel microparticles for fast visual detection of
      mercury(II) and adenosine.
AB  - With a low optical background, high loading capacity, and good biocompatibility,
      hydrogels are ideal materials for immobilization of biopolymers to develop
      optical biosensors. We recently immobilized mercury and lead binding DNAs within
      a monolithic gel and demonstrated ultrasensitive visual detection of these heavy
      metals. The high sensitivity was attributed to the enrichment of the analytes
      into the gels. The signaling kinetics was slow, however, taking about 1 h to
      obtain a stable optical signal because of a long diffusion distance. In this
      work, we aim to understand the analyte enrichment process and improve the
      signaling kinetics by preparing hydrogel microparticles. DNA-functionalized gel
      beads were synthesized using an emulsion polymerization technique and most of the
      beads were between 10 and 50 MUm. Acrydite-modified DNA was incorporated by
      copolymerization. Visual detection of 10 nM Hg(2+) was still achieved and a
      stable signal was obtained in just 2 min. The gel beads could be spotted to form
      a microarray and dried for storage. A new visual sensor for adenosine was
      designed and immobilized within the gel beads. The adenosine aptamer binds its
      target about 1000-fold less tightly compared to the mercury binding DNA, allowing
      a comparison to be made on analyte enrichment by aptamer-functionalized
      hydrogels.

PMID- 22468718
TI  - Relation of bosentan, iloprost, and sildenafil with growth factor levels in
      monocrotaline-induced pulmonary hypertension.
AB  - It is believed that growth factors play an important role in vascular remodeling
      that is evident in pulmonary hypertension (PH) pathogenesis. In the present
      study, the vascular endothelial growth factor (VEGF) levels in serum and
      pulmonary artery samples of rats have been analyzed with monocrotaline (MCT)
      induced PH after treatments with iloprost, bosentan, and sildenafil. Serum VEGF
      and pulmonary artery VEGF levels were found to be significantly lower in MCT
      groups compared with control groups and significantly higher in treatment groups
      compared with MCT groups. In conclusion, treatment strategies directed at
      increasing VEGF levels may be reasonable in PH management.

PMID- 22468719
TI  - Profiles of cognitive subtest impairment in the Montreal Cognitive Assessment
      (MoCA) in a research cohort with normal Mini-Mental State Examination (MMSE)
      scores.
AB  - The comparative ability of the Montreal Cognitive Assessment (MoCA) and MMSE to
      detect mild cognitive difficulties was investigated in 107 older adults. The
      sensitivity of the MoCA to detect cognitive impairment with a cutoff score of <26
      was investigated, as compared to the MMSE across all scores, and at a cutoff of
      >=27. Performance on MoCA subtests was compared at these MMSE cutoffs to
      determine profiles of early cognitive difficulties. The MoCA detected cognitive
      impairment not detected by the MMSE in a high proportion of participants, and
      this impairment was evident across various subtests. The MoCA appears to be a
      sensitive screening test for detection of early cognitive impairment.

PMID- 22468720
TI  - CHAOS in the mirror: Ballantyne (mirror) syndrome related to congenital high
      upper airway obstruction syndrome.
AB  - In the mirror syndrome, maternal edema mirrors fetal edema. The pathogenesis is
      unknown. The most common etiologic associations are rhesus isoimmunization, twin
      twin transfusion syndrome, and viral infections. Less than 10% of reported cases
      are associated with congenital anomalies. We report a case due to congenital
      laryngeal stenosis, which also caused congenital high airway obstruction syndrome
      (CHAOS), characterized by pulmonary hyperplasia and edema or anasarca, related to
      airway abnormality. The fetal manifestations of the mirror syndrome and CHAOS
      overlap, but occurrence of the two in the same patient does not seem to have been
      reported.

PMID- 22468721
TI  - Impact of hydrophilic/hydrophobic surface chemistry on hydration forces in the
      absence of confinement.
AB  - The oscillatory force profile, observed in liquids due to molecular ordering at
      interfaces, has been extensively investigated by means of atomic force
      microscopy, but it remains unclear whether molecular ordering is present at the
      tip apex. Using a displacement-sensitive, low-noise atomic force microscope (AFM)
      operated in dynamic mode, with a tip of radius < 1 nm, we have investigated the
      force profile between two approaching surfaces of the same or different
      hydrophilic and hydrophobic character. By directly comparing different surface
      chemistry interactions, we have been able to elucidate whether an oscillatory
      force profile is due to structured water layers adjacent to the surface, the tip,
      or a combination of the two. We have found that an oscillatory force profile is
      observed when the surface is hydrophilic in nature, irrespective of whether the
      tip is hydrophilic or hydrophobic. When the surface is hydrophobic, an
      oscillatory force profile is not measured, but rather a monotonic repulsive or a
      short-range attractive force is observed for interactions with a hydrophilic or a
      hydrophobic tip, respectively. Thus, we attribute the measurement of an
      oscillatory force profile, in the absence of lateral confinement effects, solely
      to water layers adjacent to a hydrophilic surface rather than the structuring of
      water at the tip apex. This is the first direct evidence that solvation forces
      occur solely as a result of water layers adjacent to the substrate. 

PMID- 22468722
TI  - Time- and space-order effects in timed discrimination of brightness and size of
      paired visual stimuli.
AB  - Despite the importance of both response probability and response time for testing
      models of choice, there is a dearth of chronometric studies examining systematic
      asymmetries that occur over time- and space-orders in the method of paired
      comparisons. In this study, systematic asymmetries in discriminating the
      magnitude of paired visual stimuli are examined by way of log odds ratios of
      binary responses as well as by signed response speed. Hierarchical Bayesian
      modeling is used to map response probabilities and response speed onto
      constituent psychological process, and processing capacity is also assessed using
      response time distribution hazard functions. The findings include characteristic
      order effects that change systematically in magnitude and direction with changes
      in the magnitude and separation of the stimuli. After Hellstrom (1979, 2000),
      sensation weighting (SW) model analyses show that such order effects are
      reflected in the weighted accumulation of noisy information about the difference
      between stimulus values over time, and interindividual differences in weightings
      asymmetries are related to the relative processing capacity of participants. An
      account of SW based on the use of reference level information and maximization of
      signal-to-noise ratios is posited, which finds support from theoretically driven
      analyses of behavioral data.

PMID- 22468723
TI  - Templates for rejection: configuring attention to ignore task-irrelevant
      features.
AB  - Theories of attention are compatible with the idea that we can bias attention to
      avoid selecting objects that have known nontarget features. Although this may
      underlie several existing phenomena, the explicit guidance of attention away from
      known nontargets has yet to be demonstrated. Here we show that observers can use
      feature cues (i.e., color) to bias attention away from nontarget items during
      visual search. These negative cues were used to quickly instantiate a template
      for rejection that reliably facilitated search across the cue-to-search stimulus
      onset asynchronies (SOAs), although negative cues were not as potent as cues that
      guide attention toward target features. Furthermore, by varying the search set
      size we show a template for rejection is increasingly effective in facilitating
      search as scene complexity increases. Our findings demonstrate that knowing what
      not to look for can be used to configure attention to avoid certain features,
      complimenting what is known about setting attention to select certain target
      features.

PMID- 22468724
TI  - The ineluctable modality of the audible: perceptual determinants of auditory
      verbal short-term memory.
AB  - Classical cognitive accounts of verbal short-term memory (STM) invoke an
      abstract, phonological level of representation which, although it may be derived
      differently via different modalities, is itself amodal. Key evidence for this
      view is that serial recall of phonologically similar verbal items (e.g., the
      letter sounds b, c, g, and d) is worse than that of dissimilar items, regardless
      of modality of presentation. Here we show that the effect of such phonological
      similarity in STM can be fully accounted for by the joint action of articulatory
      similarity, leading to errors in speech planning processes, and acoustic
      similarity within auditorily presented lists, which modulates their perceptual
      organization. The results indicate that key evidence used to argue for the
      existence of abstract phonological representation can in fact be fully accounted
      for by reference to modality-specific perceptual and motor planning mechanisms.

PMID- 22468725
TI  - Haptic distal spatial perception mediated by strings: point of closest approach
      and bypass distance.
AB  - Four experiments examined haptic perception of two distal spatial properties in a
      bypass event. A hook suspended a string held taut between the participant's
      finger and a weight. Moving their fingers laterally beneath the hook,
      participants estimated the finger's point of closest approach (PCA) to the hook
      and bypass distance (BPD; i.e., hook height above the finger's track at PCA).
      Experiment 1 yielded near perfect PCA estimates (group average r > .99),
      independent of BPD and traverse distance. Experiment 2 replicated PCA results,
      and showed good BPD estimates (group r = .74). BPD estimates depended on lateral
      movement distance to PCA, but not weight. In Experiment 3, feedback on accuracy
      improved BPD estimates (maximum group average R = .91). Magnitude estimation of
      BPD in Experiment 4 yielded a power law relationship (group average r = .90;
      exponent, .30). Results show that human perceivers can make effective judgments
      of PCA and BPD using haptically available force relationships. Results are
      interpreted in terms of haptics as a telemodality, the Gibsonian perceptual
      research program, and dynamic touch.

PMID- 22468726
TI  - The relationship between alertness and executive control.
AB  - The current study focuses on the relationship between alerting and executive
      attention. Previous studies reported an increased flanker congruency effect
      following alerting cues. In the first two experiments, we found that the
      alertness-congruency interaction did not exist for all executive tasks (it
      appeared for a flanker task but not for a Stroop task). In Experiments 3 and 4,
      we show that alerting increases the congruency effect in a response selection
      task only when the relevant and irrelevant information is spatially separated. We
      suggest that alerting modulates the allocation of attention by prioritizing
      processing of spatial information presented in the visual field. This process can
      be adaptive under many circumstances, but it comes at a cost. Alerting could
      possibly compromise our performance when required to filter out irrelevant
      spatial information.

PMID- 22468727
TI  - Adaptive two-dimensional microgas chromatography.
AB  - We proposed and investigated a novel adaptive two-dimensional (2-D) microgas
      chromatography system, which consists of one 1st-dimensional column, multiple
      parallel 2nd-dimensional columns, and a decision-making module. The decision
      making module, installed between the 1st- and 2nd-dimensional columns, normally
      comprises an on-column nondestructive vapor detector, a flow routing system, and
      a computer that monitors the detection signal from the detector and sends out the
      trigger signal to the flow routing system. During the operation, effluents from
      the 1st-dimensional column are first detected by the detector and, then,
      depending on the signal generated by the detector, routed to one of the 2nd
      dimensional columns sequentially for further separation. As compared to
      conventional 2-D GC systems, the proposed adaptive GC scheme has a number of
      unique and advantageous features. First and foremost, the multiple parallel
      columns are independent of each other. Therefore, their length, stationary phase,
      flow rate, and temperature can be optimized for best separation and maximal
      versatility. In addition, the adaptive GC significantly lowers the thermal
      modulator modulation frequency and hence power consumption. Finally, it greatly
      simplifies the postdata analysis process required to reconstruct the 2-D
      chromatogram. In this paper, the underlying working principle and data analysis
      of the adaptive GC was first discussed. Then, separation of a mixture of 20
      analytes with various volatilities and polarities was demonstrated using an
      adaptive GC system with a single 2nd-dimensional column. Finally, an adaptive GC
      system with dual 2nd-dimensional columns was employed, in conjunction with
      temperature ramping, in a practical application to separate a mixture of plant
      emitted volatile organic compounds with significantly shortened analysis time.

PMID- 22468728
TI  - Boyfriends and injecting: the role of intimate male partners in the life of women
      who inject drugs in Central Java.
AB  - The international literature shows that HIV-risk behaviour for women mostly
      occurs in the context of intimate relationships. Power imbalances in the social,
      economic and cultural spheres put women at risk. This paper addresses the roles
      of male partners in women's engagement in drug-use behaviour and drug-related HIV
      risk behaviour in Indonesia. Data were gathered through in-depth interviews with
      19 women who had injected drugs in the previous month in three sites in central
      Java. Most of the women had male partners who also injected drugs. Results show
      that male partners play a significant role in the initiation of drug use, the
      provision of drugs, injecting behaviour and in the constitution of women
      injectors' social networks. These findings suggest the need to develop couple
      based interventions and to facilitate women-only groups as part of HIV
      prevention.

PMID- 22468729
TI  - The intercalation of N,N,N',N'-tetramethyl-ethane-1,2-diamine (tmeda) into C6Li
      and C12Li.
AB  - Liquid N,N,N',N'-tetramethyl-ethane-1,2-diamine (tmeda) was intercalated into
      preprepared C(6)Li or C(12)Li. X-ray diffraction from the ternary compound
      indicates an identity period of 11.5 A. The (13)C NMR line shifts show that tmeda
      molecules form a screen between the graphene planes and the lithium ions. Small
      angle X-ray scattering showed that no higher structural ordering was present but
      revealed a progressive roughening of the surfaces with successive intercalation
      of lithium and amine into the graphite galleries.

PMID- 22468730
TI  - Multilocus analysis of candidate genes involved in neurogenic inflammation in
      pediatric asthma and related phenotypes: a case-control study.
AB  - OBJECTIVES: Asthma is a heterogenous complex disorder caused by chronic
      inflammation of the airways. The key issue in genetic association studies of
      complex disorders is the identification of multiple low-risk genes that
      individually have little impact on the phenotype, but in combination account for
      the clinical manifestation of asthma. Since neurogenic inflammation is emerging
      as a candidate factor in the pathogenesis of asthma, the aim of the study was to
      investigate whether genetic variants of neurotrophin genes are associated with
      asthma disease severity or asthma-related phenotypes in a pediatric population.
      METHODS: We genotyped 27 polymorphisms located in neurotrophin genes, using
      TaqMan SNP genotyping assays or Polymerase Chain Reaction - Restriction Fragments
      Lengths Polymorphism (PCR-RFLP) in 200 children diagnosed with asthma and 226
      controls. Interactions between 27 polymorphic loci and asthma-related phenotypes
      were determined using the Multifactor Dimensionality Reduction (MDR) method.
      RESULTS: In single marker analysis, we observed an association of MAP3K1 gene
      polymorphisms (rs702689 and rs889312) with asthma. We also observed that four
      Single Nucleotide Polymorphisms (SNPs) were associated with severe asthma.
      Analysis stratified by asthma-related phenotype revealed an association between
      atopy and NGFR (rs3785931), while BDNF (rs7124442), NTRK2 (rs1212171), NGFR
      (rs2072446), and FYN (rs3730353) variants were associated with increased exhaled
      nitric oxide (exNO). In addition, gene-gene interaction analysis revealed a
      significant epistatic interaction between MAPK (rs889312) and NGF (rs11102930)
      variants in asthma susceptibility. CONCLUSIONS: Our results suggest that genetic
      variants of MAP3K1 and NGF genes involved in the regulation of neurogenic
      inflammation may contribute to asthma, possibly via enhanced NGF expression and
      MAPK signaling pathway activation.

PMID- 22468731
TI  - Rosiglitazone prior authorization safety policy: a cohort study.
AB  - BACKGROUND: Prior authorizations (PA) are intended to promote safe and cost
      effective medication use. Unwanted outcomes may occur, however, such as a patient
      forgoing drug therapy after a PA. The label for rosiglitazone was revised in
      November 2007 to include the warning of contraindicated use with nitrates or
      insulin, creating an opportunity for a PA directed at safe use. OBJECTIVE: To
      evaluate antidiabetic drug utilization after the implementation of an electronic
      PA that denied a claim for rosiglitazone if the patient had a history of either
      insulin or nitrate supply in the previous 60 days. METHODS: This quasi
      experimental study used pharmacy claims for 1.4 million commercially insured
      members who were exposed to a rosiglitazone PA beginning on January 1, 2009,
      compared with a group of approximately 2 million commercially insured members who
      did not have this safety PA intervention. Continuously enrolled members were
      identified who had a rejected (intervention group) or paid (comparison group)
      claim for rosiglitazone during the period from January 1, 2009, through June 30,
      2009. Pharmacy claims were assessed for the presence of nitrates, insulin,
      rosiglitazone, other antidiabetic therapy, or no antidiabetic therapy supply on
      days 30, 60, 90, and 180 after the rejected/paid claim. A time-series analysis
      using rosiglitazone claims for all health plan members from January 2008 through
      December 2009 was used to evaluate the impact of the PA on rosiglitazone
      utilization overall. RESULTS: At 30 days, there were 134 patients (60.4% of 222)
      in the comparison group with concurrent supply of rosiglitazone with insulin
      and/or nitrates versus 4 patients (2.4% of 168, P  less than  0.001) in the PA
      intervention group, and the utilization rate remained significantly higher at 180
      days in the comparison group (37.8%, n = 84) versus the PA group (2.4%, n = 4, P 
      less than  0.001). Beginning at 60 days, there was no significant difference in
      the percentage of members with no antidiabetic therapy in the comparison and PA
      intervention groups (9.9% vs. 15.5%, respectively, P = 0.133), and the rates
      remained similar through 180 days (15.3% vs. 13.7%, respectively, P = 0.760). The
      PA was associated with an absolute decrease of 5.1 average monthly rosiglitazone
      claims per day per million members (P  less than  0.001). CONCLUSIONS: This PA,
      intended to reduce known cardiovascular event risks among health plan members
      with type 2 diabetes, was associated with a significant reduction in concurrent
      use of rosiglitazone with nitrates or insulin.

PMID- 22468732
TI  - Acute and chronic acetaminophen use and renal disease: a case-control study using
      pharmacy and medical claims.
AB  - BACKGROUND: Studies have examined the association between acetaminophen (APAP)
      use and renal disease; however, their interpretation is limited by a number of
      methodological issues. OBJECTIVE: To study the association between acute and
      chronic prescription-acquired APAP use and renal disease. METHODS: This was a
      retrospective case-control study of medical and pharmacy claims of a 10% random
      sample of the enrollees from the IMS LifeLink Health Plans commercial claims
      dataset for dates of service from January 1, 1997, through December 31, 2009.
      Subjects were continuously enrolled and aged 18 years or older. Cases had at
      least 1 incident claim of renal disease defined by ICD-9-CM codes in the primary
      diagnosis field. Controls were randomly selected from individuals without
      evidence of renal disease, liver disease, or asthma in medical claims and matched
      to cases in a 3-to-1 ratio based on 3 variables (age, gender, and geographic
      region). APAP exposure, dosage, and duration of use were measured in the 7 and 30
      days (acute) and in the 1-year (chronic) look-back periods. Multivariable
      conditional logistic regression was used to estimate the risk of APAP exposure
      adjusted for comorbidities, use of other nephrotoxic drugs, and health system
      factors. RESULTS: There were 4,724 cases and 14,172 controls with a mean (SD) age
      of 60.8 (17.8) years, and 52.6% were males; 10.9% of cases and 4.2% of controls
      had APAP exposure in the 30 days pre-index with mean potential maximum daily
      dosages of 3,846.5 mg and 3,190.8 mg, respectively. Acute APAP exposure was
      significantly associated with renal disease, and the risk decreased with longer
      look-back periods (7 days: adjusted odds ratio [OR] = 1.93, 95% CI = 1.61-2.30);
      30 days: OR = 1.71, 95% CI = 1.48-1.97). Cumulative APAP dosage greater than 1 kg
      and APAP use for longer than 30 days in the pre-index year were not significantly
      associated with an increased risk of renal disease (both P values = 0.900).
      CONCLUSIONS: Acute prescription-acquired APAP use was associated with renal
      disease, while chronic use was not. Because this study assessed APAP use in
      pharmacy claims, further research accounting for over-the-counter APAP use is
      warranted before the safety of chronic APAP consumption can be firmly
      established.

PMID- 22468733
TI  - Community pharmacy and mail order cost and utilization for 90-day maintenance
      medication prescriptions.
AB  - BACKGROUND: Pharmacy benefit management (PBM) companies promote mail order
      programs that typically dispense 90-day quantities of maintenance medications,
      marketing this feature as a key cost containment strategy to address plan
      sponsors' rising prescription drug expenditures. In recent years, community
      pharmacies have introduced 90-day programs that provide similar cost advantages,
      while allowing these prescriptions to be dispensed at the same pharmacies that
      patients frequent for 30-day quantities. OBJECTIVE: To compare utilization rates
      and corresponding costs associated with obtaining 90-day prescriptions at
      community and mail order pharmacies for payers that offer equivalent benefits in
      different 90-day dispensing channels. METHODS: We performed a retrospective,
      cross-sectional investigation using pharmacy claims and eligibility data from
      employer group clients of a large PBM between January 2008 and September 2010. We
      excluded the following client types: government, third-party administrators,
      schools, hospitals, 340B (federal drug pricing), employers in Puerto Rico, and
      miscellaneous clients for which the PBM provided billing services (e.g., the
      pharmacy's loyalty card program members). All employer groups in the sample
      offered 90-day community pharmacy and mail order dispensing and received benefits
      management services, such as formulary management and mail order pharmacy, from
      the PBM. We further limited the sample to employer groups that offered equivalent
      benefits for community pharmacy and mail order, defined as groups in which the
      mean and median copayments per claim for community and mail order pharmacy, by
      tier, differed by no more than 5%. Enrollees in the sample were required to have
      a minimum of 6 months of eligibility in each calendar year but were not required
      to have filled a prescription in any year. We evaluated pharmacy costs and
      utilization for a market basket of 14 frequently dispensed therapeutic classes of
      maintenance medications. The proportional share of claims for each therapeutic
      class in the mail order channel was used to weight the results for the community
      pharmacy channel. Using ordinary least squares regression models, we controlled
      for differences between channel users with respect to the following confounding
      factors: age, gender, presence or absence of each of the top 11 drug-inferred
      conditions (e.g., asthma/chronic obstructive pulmonary disease, cardiovascular
      disease), drug mix, and calendar year. We calculated estimated predicted means
      holding all covariates at their mean values. For both 90-day dispensing channels,
      we calculated number of 90-day claims per member per year (PMPY) and cost per
      pharmacy claim, with all claims counts adjusted to 30-day equivalents (i.e.,
      number of 90-day claims * 3). Differences were compared using t-tests for
      statistical significance. RESULTS: Of 355 PBM clients prior to exclusions, 72
      unique employers covering 644,071 unique members (range of approximately 100 to
      more than 100,000 members per employer) were included in the analysis. On an
      unadjusted basis, community pharmacies represented 80.8% of 90-day market basket
      claims (in 30-day equivalents: 3.97 claims PMPY vs. 0.95 in mail order) and 77.2%
      of total allowed charges. After adjustments for therapeutic group mix and patient
      characteristics, predicted mean pharmacy claim counts PMPY were 4.09 for
      community pharmacy compared with 0.85 for mail order (P  less than  0.001).
      Predicted mean allowed charges per claim for community and mail order pharmacies
      did not significantly differ ($49.03 vs. $50.04, respectively, P = 0.202).
      CONCLUSIONS: When offered maintenance medications through community and mail
      order pharmacies on a benefit-equivalent basis, commercially insured employees
      and their dependents utilized the community pharmacy channel more frequently by a
      margin of more than 4 to 1 in terms of claims PMPY. Overall allowed charges per
      claim for community and mail order pharmacy did not significantly differ.

PMID- 22468734
TI  - Pharmaceutical technology assessment: perspectives from payers.
AB  - BACKGROUND: Advancements in biologics and personalized medicine and the
      implementation of national prescription drug policies have likely prompted payers
      to implement additional health technology assessment and cost-containment
      strategies. A payer's decision to provide coverage for a drug and its associated
      benefit design draws on information from many sources. However, there is an
      incomplete understanding of the process employed and the criteria applied in
      formulary assessments of pharmaceuticals by public and private health plans.
      OBJECTIVES: To explore the pharmaceutical technology assessment (PTA) process to
      determine (a) who is involved in the decision making, (b) the timing and process
      of assessment and decision making, (c) the information and data that are
      considered, and (d) the outcomes of the assessment. METHODS: Using a convenience
      sample drawn for exploratory purposes, we targeted health plans, pharmacy benefit
      management (PBM) companies, stand-alone Medicare Part D prescription drug plans,
      Medicaid agencies, and drug compendia. We used multiple approaches to identify
      and recruit medical and pharmacy directors responsible for prescription drug
      benefit design and formulary management. We conducted 1-hour semistructured
      telephone interviews with pharmacy benefit decision makers between November 2009
      and April 2010 to address the PTA process, and they rated the importance of
      different sources and types of evidence. Qualitative analysis and descriptive
      statistics were used to explore coverage, preferred choice, and utilization
      management. RESULTS: Thirty-two respondents representing 26 organizations
      participated in the interview. On a scale from 1 to 5 (not important to very
      important), interview respondents most valued published peer-reviewed studies,
      technology assessments, and internal data on drug utilization as sources of
      information (means = 4.68, 4.22, and 4.14, respectively). Randomized controlled
      trials (RCTs) and systematic reviews/meta-analyses were the most valued types of
      evidence (means = 4.40 and 3.66, respectively); economic and observational data
      studies received low ratings (means = 3.19 and 3.03, respectively). There was
      substantial variation in the process of evidence review, who and how individuals
      participated in the process, and outcomes related to formulary tier placement and
      utilization management. CONCLUSIONS: U.S. health plan payers have established
      processes for PTA and prefer certain sources and types of evidence. Formulary
      decision makers value a broad range of information, and the specific factors
      influencing coverage and utilization management decisions vary across
      organizations and therapeutic areas.

PMID- 22468735
TI  - Payer perspectives on health technology assessment.

PMID- 22468736
TI  - Implications of Risk Evaluation and Mitigation Strategy (REMS) programs for
      managed care pharmacy.
AB  - In the last 2 decades, health care management has been challenged by more
      aggressive therapy, the increased number of specialty medications, and more
      stringent guidelines to monitor adverse events or health risk. To promote patient
      safety, various communication requirements are mandated to increase the risk
      awareness of patients and physicians. These include black-box warnings, "Dear
      Health Care Provider" letters, U.S. Food and Drug Administration (FDA) Talk
      Papers, MedGuides, and Risk Minimization Action Plans (RiskMAPs).

PMID- 22468737
TI  - Consensus statements from a panel of U.S. managed care pharmacists and physicians
      for management of multiple sclerosis agents.

PMID- 22468738
TI  - Consensus statements from a panel of U.S. managed care pharmacists and physicians
      for management of multiple sclerosis agents.

PMID- 22468739
TI  - Association of age, gender, and race with intensity of end-of-life care for
      Medicare beneficiaries with cancer.
AB  - PURPOSE: To measure intensity of end-of-life (EOL) care for Medicare cancer
      patients and variations in care by age, gender, and race. PATIENTS AND METHODS:
      This retrospective cohort analysis of Medicare claims (20% sample) examined
      235,821 Medicare Parts A and B fee-for-service patients dying with poor-prognosis
      cancers between 2003 and 2007. Logistic regression models quantified associations
      between care intensity and age, gender, and race. Measures included
      hospitalizations, emergency department (ED) visits, intensive care unit (ICU)
      admissions, in-hospital deaths, late-life chemotherapy administration, overall
      and late hospice enrollment within six months of death. RESULTS: Within 30 days
      of death, 61.3% of patients were hospitalized, 10.2% were hospitalized more than
      once, 10.2% visited an ED more than once, 23.7% had ICU admissions, and 28.8%
      died in-hospital. Within two weeks of death, 6% received chemotherapy. In their
      final six months, 55.2% accessed hospice, 15.1% within three days of death. Older
      age (>=75 versus <75) was associated with lower odds ratios (ORs) of 0.49 to 0.89
      for aggressive care, and an OR of 0.92 (95% CI 0.89-0.95) for late hospice
      enrollment. Female gender was associated with lower ORs (0.82 to 0.86) for
      aggressive care, and an OR of 0.84 (95% CI 0.81-0.86) for late hospice
      enrollment. Black (versus nonblack) race was associated with higher ORs (1.08 to
      1.38) for aggressive acute care, lower ORs for late chemotherapy, OR 0.76 (95% CI
      0.71-0.81), and late hospice enrollment, OR 0.81 (95% CI 0.76-0.86). CONCLUSIONS:
      Seniors dying with poor-prognosis cancer experience high-intensity care with
      rates varying by age, gender, and race.

PMID- 22468740
TI  - Direct imaging of atomic-scale ripples in few-layer graphene.
AB  - Graphene has been touted as the prototypical two-dimensional solid of
      extraordinary stability and strength. However, its very existence relies on out
      of-plane ripples as predicted by theory and confirmed by experiments. Evidence of
      the intrinsic ripples has been reported in the form of broadened diffraction
      spots in reciprocal space, in which all spatial information is lost. Here we show
      direct real-space images of the ripples in a few-layer graphene (FLG) membrane
      resolved at the atomic scale using monochromated aberration-corrected
      transmission electron microscopy (TEM). The thickness of FLG amplifies the weak
      local effects of the ripples, resulting in spatially varying TEM contrast that is
      unique up to inversion symmetry. We compare the characteristic TEM contrast with
      simulated images based on accurate first-principles calculations of the
      scattering potential. Our results characterize the ripples in real space and
      suggest that such features are likely common in ultrathin materials, even in the
      nanometer-thickness range.

PMID- 22468741
TI  - Plant proteins, minerals and trace elements of Eurycoma longifolia (Tongkat Ali).
AB  - A water extraction method has been used to extract plant proteins from the roots
      of Eurycoma longifolia harvested from Perak and Pahang, Malaysia. On the basis of
      the spectroscopic Bradford assay, Tongkat Ali Perak and Pahang contained 0.3868
      and 0.9573 mg mL(-1) of crude protein, respectively. The crude proteins were
      separated by one dimensional 15% sodium dodecyl sulphate polyacrylamide gel
      electrophoresis into two (49.8 and 5.5 kD) and four (49.8, 24.7, 21.1 and 5.5 kD)
      protein spots for Tongkat Ali Perak and Pahang, respectively. Isoleucine was
      present in the highest concentration significantly. Both plant samples showed
      differences in the mineral and trace element profiles, but the minerals calcium,
      magnesium and potassium were present in the highest concentration. The highly
      concerned toxic metals such as arsenic and lead were not detected.

PMID- 22468742
TI  - In situ growth of metal particles on 3D urchin-like WO3 nanostructures.
AB  - Metal/semiconductor hybrid materials of various sizes and morphologies have many
      applications in areas such as catalysis and sensing. Various organic agents are
      necessary to stabilize metal nanoparticles during synthesis, which leads to a
      layer of organic compounds present at the interfaces between the metal particles
      and the semiconductor supports. Generally, high-temperature oxidative treatment
      is used to remove the organics, which can extensively change the size and
      morphology of the particles, in turn altering their activity. Here we report a
      facile method for direct growth of noble-metal particles on WO(3) through an in
      situ redox reaction between weakly reductive WO(2.72) and oxidative metal salts
      in aqueous solution. This synthetic strategy has the advantages that it takes
      place in one step and requires no foreign reducing agents, stabilizing agents, or
      pretreatment of the precursors, making it a practical method for the controlled
      synthesis of metal/semiconductor hybrid nanomaterials. This synthetic method may
      open up a new way to develop metal-nanoparticle-loaded semiconductor composites.

PMID- 22468743
TI  - Probing the self-assembly mechanism of diphenylalanine-based peptide nanovesicles
      and nanotubes.
AB  - Nanostructures, particularly those from peptide self-assemblies, have attracted
      great attention lately due to their potential applications in nanotemplating and
      nanotechnology. Recent experimental studies reported that diphenylalanine-based
      peptides can self-assemble into highly ordered nanostructures such as
      nanovesicles and nanotubes. However, the molecular mechanism of the self
      organization of such well-defined nanoarchitectures remains elusive. In this
      study, we investigate the assembly pathway of 600 diphenylalanine (FF) peptides
      at different peptide concentrations by performing extensive coarse-grained
      molecular dynamics (MD) simulations. Based on forty 0.6-1.8 MUs trajectories at
      310 K starting from random configurations, we find that FF dipeptides not only
      spontaneously assemble into spherical vesicles and nanotubes, consistent with
      previous experiments, but also form new ordered nanoarchitectures, namely, planar
      bilayers and a rich variety of other shapes of vesicle-like structures including
      toroid, ellipsoid, discoid, and pot-shaped vesicles. The assembly pathways are
      concentration-dependent. At low peptide concentrations, the self-assembly
      involves the fusion of small vesicles and bilayers, whereas at high
      concentrations, it occurs through the formation of a bilayer first, followed by
      the bending and closure of the bilayer. Energetic analysis suggests that the
      formation of different nanostructures is a result of the delicate balance between
      peptide-peptide and peptide-water interactions. Our all-atom MD simulation shows
      that FF nanostructures are stabilized by a combination of T-shaped aromatic
      stacking, interpeptide head-to-tail hydrogen-bonding, and peptide-water hydrogen
      bonding interactions. This study provides, for the first time to our knowledge,
      the self-assembly mechanism and the molecular organization of FF dipeptide
      nanostructures.

PMID- 22468744
TI  - Phase II study of gemcitabine and docetaxel in recurrent platinum resistant
      ovarian cancer.
AB  - To evaluate the activity of gemcitabine and docetaxel in patients with recurrent
      ovarian cancer. METHODS: Patients with platinum-resistant disease and prior
      treatment with paclitaxel received treatment with docetaxel on day 1 and
      gemcitabine on days 1 and 8, repeated every three weeks. RESULTS: Twenty
      patients, with a platinum-free interval of three months, were enrolled. Overall
      response rate was 25%. Treatment was associated with significant
      myelosuppression. CONCLUSIONS: In chemotherapy-resistant patients, this regimen
      exhibited encouraging activity. Excessive myelosuppression led to early closure.
      This was prevented by administering docetaxel on day 8 (instead of day 1) and
      prophylactic use of G-CSF.

PMID- 22468745
TI  - Design, synthesis and in vivo/in vitro screening of novel chlorokojic acid
      derivatives.
AB  - A series of novel Mannich bases of chlorokojic acid (2-chloromethyl-5-hydroxy-4H
      pyran-4-one) were synthesized and their biological activities were investigated.
      Anticonvulsant activity results according to phase-I tests of Antiepileptic Drug
      Development (ADD) Program revealed that compound 13 was the most effective one at
      4 h against subcutaneous pentylenetetrazole (scPTZ)-induced seizure test.
      Antimicrobial activities were evaluated in vitro against bacteria and fungi by
      using broth microdilution method. The antitubercular activities against
      Mycobacterium tuberculosis and M. avium were discussed with Resazurin microplate
      assay (REMA). The antimicrobial activity results indicated that compounds 1 and
      12 (MIC: 8-16 ug/mL) showed higher activity against Gram negative bacteria while
      compound 12 had MIC: 4-16 ug/mL against Gram positive bacteria. Compound 1 was
      the most active one with MIC values of 8-32 ug/mL against fungi. Mannich bases
      also exhibit significant antitubercular activity in a MIC range of 4 to 32 ug/mL,
      especially compound 18 against M. avium.

PMID- 22468746
TI  - (3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone and its derivatives as
      carbonic anhydrase isoenzymes inhibitors.
AB  - In this study, we have synthesised (3,4-dihydroxyphenyl)(2,3,4
      trihydroxyphenyl)methanone and a series of its derivatives (5, 13-16) and 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. The synthesised compounds
      showed inhibitory effect on hCA I and hCA II isozymes. The results showed that
      synthesised compounds (5, 13-16) demonstrated the best inhibition activity
      against hCA I (IC(50): 3.22-54.28 MUM) and hCA II (IC(50): 18.52-142.01 MUM). The
      compound 14 showed the highest inhibiton effect against hCA I (IC(50): 3.22 MUM;
      K(i): 1.19 +/- 1.4 MUM). On the other hand, the compound 13 showed the highest
      inhibiton effect against hCA II (IC(50): 18.52 MUM; K(i): 3.25 +/- 1.13 MUM).

PMID- 22468747
TI  - Structure-based drug discovery of carbonic anhydrase inhibitors.
AB  - Inhibition of the metalloenzyme carbonic anhydrase (CA; EC 4.2.1.1) has
      pharmacologic applications in the field of anti-glaucoma, anti-convulsant and
      anti-cancer agents. But recently, it has also emerged that these enzymes have the
      potential for designing anti-infective drugs (anti-fungal and anti-bacterial
      agents) with a novel mechanism of action. Sulphonamides and their isosteres
      (sulphamates/sulphamides) constitute the main class of CA inhibitors (CAIs),
      which bind to the metal ion from the enzyme active site. Recently, the
      dithiocarbamates (DTCs), possessing a similar mechanism of action, were reported
      as a new class of inhibitors. These types of CAIs will be discussed in detail in
      this review. Novel drug design strategies have been reported ultimately based on
      the tail approach for obtaining sulphonamides/DTCs, which exploit more external
      binding regions within the enzyme active site (in addition to coordination to the
      metal ion), leading thus to isoform-selective compounds. Most of the promising
      data have been obtained by combining x-ray crystallography of enzyme-inhibitor
      adducts with novel synthetic approaches for generating chemical diversity.
      Whereas sulphonamide - NO donating hybrid drugs were reported as effective anti
      glaucoma agents, most of the interesting new inhibitors were designed for
      inhibiting specifically the tumour-associated isoforms CA IX and XII, validated
      targets for imaging and treatment of hypoxic tumours. Promising compounds that
      inhibit CAs from bacterial and fungal pathogens, of the DTC and carboxylate
      types, will be also reviewed.

PMID- 22468748
TI  - 2,2'-Dithienyl diselenide, an organoselenium compound, elicits antioxidant action
      and inhibits monoamine oxidase activity in vitro.
AB  - CONTEXT: Organoselenium compounds have been described as antioxidant and
      neuroprotective agents. OBJECTIVE: To evaluate the antioxidant action of 2,2'
      dithienyl diselenide (DTDS) and its effects in brain monoamine oxidase (MAO)
      activity in vitro. MATERIALS AND METHODS: Assays for reactive species (RS), lipid
      peroxidation, protein oxidation, MAO A and B activities in rat brain homogenate
      as well as mimetic dehydroascorbate reductase and glutathione S-transferase
      activities were performed using DTDS (MUM range). RESULTS: DTDS was effective in
      decreasing the levels of RS as well as lipid peroxidation induced by malonate,
      sodium nitroprusside or FeCl2/EDTA and protein carbonyl in the rat brain
      homogenate. DTDS elicited dehydroascorbate reductase-like and glutathione S
      transferase-like activities. DTDS was effective in inhibiting both MAO-A and MAO
      B activities. DISCUSSION: The results demonstrated that DTDS is an antioxidant
      agent with non-selective inhibitory effect on MAO activity. CONCLUSION: DTDS is a
      promising molecule to be evaluated in experimental models of neurological
      diseases.

PMID- 22468749
TI  - Synthesis and biological evaluation of 5-fluoroquinolone-3-carboxylic acids as
      potential HIV-1 integrase inhibitors.
AB  - A series of new quinolone-3-carboxylic acids as HIV-1 integrase inhibitors
      featuring a fluorine atom at C-5 position were synthesized and evaluated for
      their antiviral activity in C8166 cell culture. These newly synthesized compounds
      showed anti-HIV activity against wild-type virus with an EC50 value ranging from
      29.85 to 0.032 MUMU. The most active compound 4e exhibited activity against wild
      type virus and the mutant virus A17 with an EC50 value of 0.032 and 0.082 MUMU,
      respectively. Preliminary structure-activity relationship of these 5
      fluoroquinolone-3-carboxylic acids was also investigated.

PMID- 22468750
TI  - Tyrosinase inhibitory activities of the compounds isolated from Neolitsea
      aciculata (Blume) Koidz.
AB  - This study was designed to investigate the mushroom tyrosinase inhibitory
      activity for the constituents isolated from Neolitsea aciculata. The stems of N.
      aciculata was extracted with aqueous ethanol and subjected to chromatographic
      separation, which led to the isolation of 11 compounds: methyl linoleate (1),
      catechin (2), epicatechin (3), afzelin-7-O-glucopyranoside (4), 2',3'-di-(p
      coumaroyl)afzelin (5), 2'-p-coumaroylafzelin (6), feruloyl tyramine (7), beta
      sitosterol (8), daucosterol (9), oleic acid (10), and trilaurin (11). Their
      structures were elucidated on the basis of spectroscopic studies as well as by
      comparison with the data available in the literature. Among these isolates,
      compounds 5 and 6 were identified as potent mushroom tyrosinase inhibitors with
      IC50 values of 0.067 and 0.080 mM, respectively. The inhibition kinetics,
      analysed by Lineweaver-Burk plots, indicated that compounds 5 and 6 are
      competitive tyrosinase inhibitors when using l-tyrosine as a substrate. Notably,
      compounds 1-11 were isolated for the first time from this plant. These results
      provide evidence that this plant might be a potential source of anti
      melanogenesis agents.

PMID- 22468751
TI  - Inhibition of cysteine proteases by a natural biflavone: behavioral evaluation of
      fukugetin as papain and cruzain inhibitor.
AB  - Cruzain is the major cysteine protease of Trypanosoma cruzi, the infectious agent
      responsible for Chagas disease, and cruzain inhibitors display considerable
      antitrypanosomal activity. In the present work we elucidated crystallographic
      data of fukugetin, a biflavone isolated from Garcinia brasiliensis, and
      investigated the role of this molecule as cysteine protease inhibitor. The
      kinetic analyses demonstrated that fukugetin inhibited cruzain and papain by a
      slow reversible type inhibition with K(I) of 1.1 and 13.4 uM, respectively.
      However, cruzain inhibition was about 12 times faster than papain inhibition.
      Lineweaver-Burk plots demonstrated partial competitive inhibition for cruzain and
      hyperbolic mixed-type inhibition for papain. Furthermore, the docking results
      showed that the biflavone binds to ring C' in the S2 pocket and to ring C in the
      S3 pocket through hydrophobic interactions and hydrogen bonds. Finally, fukugetin
      also presented inhibitory activity on proteases of the T. cruzi extract, with
      IC50 of 7 uM.

PMID- 22468752
TI  - Quinazoline-sulfonamides as potential antitumor agents: synthesis and biological
      testing.
AB  - New series of quinazoline containing sulfonamide derivatives were prepared and
      screened for their antitumor activity. Four human cancer cell lines, namely,
      hepatoma cancer cell line (HepG2), breast cancer cell line (MCF-7), cervix cancer
      cell line (HeLa) and colon cancer cell line (HCT-8), were used to measure the
      cytotoxic activity. Compounds 8 and 21 exhibited remarkable antitumor activity
      almost similar to that of the standard drug (doxorubicin). Six compounds 16, 22,
      23, 29, 30 and 33, showed considerable activity and few compounds were totally
      inactive.

PMID- 22468753
TI  - Photostimulated reduction of nitriles by SmI2.
AB  - Despite their high electron-withdrawing strength, nitriles are not good electron
      acceptors and therefore are hard to reduce. In this work, using photostimulation
      in the visible region, we examined the reactivity of aliphatic and aromatic, mono
      and dicyano compounds in reaction with SmI(2). A proton donor that complexes
      efficiently with SmI(2) must be used. Maximum yield was obtained at ca.0.2 M
      MeOH. Aromatic nitriles were more reactive than aliphatic nitriles, which
      exhibited negligible yields. Phenylacetonitrile presents an intermediate
      reactivity. The mechanism of the reaction involves coordination of the SmI(2) to
      the lone pair of the nitrile nitrogen followed by an inner sphere electron
      transfer. Surprisingly, m-dicyanobenzene was less reactive than the monocyano
      derivative benzonitrile. This was traced to the lower ability of the dicyano
      compound to coordinate to the SmI(2) due to, as was shown by quantum mechanical
      calculations, its lone pair having an energy significantly lower than that of
      benzonitrile. It is noteworthy that at the SmI(2) initial concentration used
      (0.04M), light penetrates only the 0.4 mm outer layer of the reaction mixture.
      Therefore the photostimulation effect observed was due to irradiation of only 4%
      of the total reaction volume, implying that under optimal conditions the effect
      should be 25 times larger.

PMID- 22468754
TI  - Characterization of domain-peptide interaction interface: prediction of SH3
      domain-mediated protein-protein interaction network in yeast by generic structure
      based models.
AB  - Determination of the binding specificity of SH3 domain, a peptide recognition
      module (PRM), is important to understand their biological functions and
      reconstruct the SH3-mediated protein-protein interaction network. In the present
      study, the SH3-peptide interactions for both class I and II SH3 domains were
      characterized by the intermolecular residue-residue interaction network. We
      developed generic MIEC-SVM models to infer SH3 domain-peptide recognition
      specificity that achieved satisfactory prediction accuracy. By investigating the
      domain-peptide recognition mechanisms at the residue level, we found that the
      class-I and class-II binding peptides have different binding modes even though
      they occupy the same binding site of SH3. Furthermore, we predicted the potential
      binding partners of SH3 domains in the yeast proteome and constructed the SH3
      mediated protein-protein interaction network. Comparison with the experimentally
      determined interactions confirmed the effectiveness of our approach. This study
      showed that our sophisticated computational approach not only provides a powerful
      platform to decipher protein recognition code at the molecular level but also
      allows identification of peptide-mediated protein interactions at a proteomic
      scale. We believe that such an approach is general to be applicable to other
      domain-peptide interactions.

PMID- 22468755
TI  - Effects of hyperoxia during recovery from 5*30-s bouts of maximal-intensity
      exercise.
AB  - We test the hypothesis that breathing oxygen-enriched air (F(I)O(2) = 100%)
      maintains exercise performance and reduces fatigue during intervals of maximal
      intensity cycling. Ten well-trained male cyclists (age 25 +/- 3 years; peak
      oxygen uptake 64.8 +/- 6.2 ml . kg(-1) . min(-1); mean +/- s) were exposed to
      either hyperoxic or normoxic air during the 6-min intervals between five 30-s
      sessions of cycling at maximal intensity. The concentrations of lactate and
      hydrogen ions [H(+)], pH, base excess, oxygen partial pressure, and oxygen
      saturation in the blood were assessed before and after these sprints. The peak (P
      = 0.62) and mean power outputs (P = 0.83) with hyperoxic and normoxic air did not
      differ. The partial pressure of oxygen was 4.2-fold higher after inhaling
      hyperoxic air, whereas lactate concentration, pH, [H(+)], and base excess (P >=
      0.17) were not influenced. Perceived exertion towards the end of the 6-min
      periods after the fourth and fifth sprints (P < 0.05) was lower with hyperoxia
      than normoxia (P < 0.05). These findings demonstrate that the peak and mean power
      outputs of athletes performing intervals of maximal-intensity cycling are not
      improved by inhalation of oxygen-enriched air during recovery.

PMID- 22468756
TI  - Physical origin of general oscillation of structure, surface energy, and
      electronic property in rutile TiO2 nanoslab.
AB  - Titanium oxide (TiO(2)) nanostructures have been attracting consistent focus in
      the past few years because of their enhanced power in solar-energy conversion.
      Surface and interface play a crucial role in the determination of thermodynamic
      stability and electronic structure of TiO(2) nanostructures. The rutile (110)
      nanoslab (NS) has been used as a common subject to investigate the surface
      relaxation, defect characters, molecule adsorption, and chemically dynamic
      reaction of TiO(2) nanostructures. Up to date, a long-time standing issue in
      TiO(2) NS, i.e., the general oscillation of structure, surface energy and
      electronic property with changing of NS thickness, has not been clear. We have
      presented a comprehensive investigation on the relationship between surface and
      oscillation behavior in the TiO(2) (110) NS by the first-principles calculations
      accompanied with the wave function analysis. We clearly, for the first time,
      pointed out that the dipoles and surface states bonding induced by the surface
      surface interactions are the physical origin of general oscillations in the
      TiO(2) (110) NS. Our findings not only have a new insight into the basic
      interactions between surfaces in TiO(2) nanostructures, but also provide useful
      information for tuning the photocatalytic and photovoltaic properties by surface
      design.

PMID- 22468757
TI  - Medicinal chemistry of A3 adenosine receptor modulators: pharmacological
      activities and therapeutic implications.

PMID- 22468758
TI  - The information gained from witnesses' responses to an initial "blank" lineup.
AB  - Wells ("The psychology of lineup identifications," Journal of Applied Social
      Psychology, 1984, 14, 89-103) proposed that a blank lineup (an initial lineup of
      known-to-be-innocent foils) can be used to screen eyewitnesses; witnesses who
      chose from a blank lineup (initial choosers) were more likely to make an error on
      a second lineup that contained a suspect than were witnesses who rejected a blank
      lineup (initial nonchoosers). Recent technological advances (e.g., computer
      administered lineups) may overcome many of the practical difficulties cited as a
      barrier to the use of blank lineups. Our research extended knowledge about the
      blank lineup procedure by investigating the underlying causes of the difference
      in identification performance between initial choosers and initial nonchoosers.
      Studies 1a and 1b (total, N = 303) demonstrated that initial choosers were more
      likely to reject a second lineup than initial nonchoosers and witnesses who did
      not view a blank lineup, implying that cognitive biases (e.g., confirmation bias
      and commitment effects) influenced initial choosers' identification decisions. In
      Study 2 (N = 200), responses on a forced-choice identification test provided
      evidence that initial choosers have, on average, poorer memories for the culprit
      than do initial nonchoosers. We also investigated the usefulness of blank lineups
      for interpreting identification evidence. Diagnosticity ratios suggested that
      suspect identifications made by initial nonchoosers (cf. initial choosers) should
      have a greater impact on estimates of the likely guilt of the suspect.
      Furthermore, for initial nonchoosers, higher confidence in blank lineup
      rejections was associated with higher diagnosticity for subsequent suspect
      identifications. These results have implications for policy to guide the
      collection and interpretation of identification evidence.

PMID- 22468759
TI  - The effect of attorneys' work with trauma-exposed clients on PTSD symptoms,
      depression, and functional impairment: a cross-lagged longitudinal study.
AB  - To date, few studies have examined mental health consequences among attorneys
      exposed to clients' traumatic experiences. A longitudinal, 2-wave, cross-lagged
      study was used in a cohort of attorneys (N = 107) from the Wisconsin State Public
      Defender's Office. We assessed changes in posttraumatic stress disorder (PTSD),
      depression, and functional impairment over a 10-month period and tested the
      effects of intensity of contact with trauma-exposed clients on symptom levels
      over time. Attorneys demonstrated strong and significant symptom stability over
      time in PTSD, depression, functional impairment, and levels of exposure. Analyses
      involving cross-lagged panel correlation structural equation modeling path models
      revealed that attorneys' levels of exposure to trauma-exposed clients had
      significant positive effects, over time, on PTSD, depression, and functional
      impairment. Gender, age, years on the job, and office size did not predict any of
      the outcomes. Level of exposure to trauma-exposed clients predicted reduction of
      weekly working hours over time, but there was no reciprocal relationship between
      PTSD, depression, and functional impairment and level of exposure over time.
      These findings underscore the central role of exposure to trauma-exposed clients
      in predicting mental health outcomes and emphasize the need to support attorneys
      by managing the intensity of exposure as well as addressing emerging symptoms.

PMID- 22468760
TI  - How do probation officers assess and manage recidivism and violence risk for
      probationers with mental disorder? An experimental investigation.
AB  - Persons with mental disorder are overrepresented in the criminal justice system.
      Once involved in the criminal justice system, offenders with mental disorder are
      more likely to return to custody while on probation than their nondisordered
      counterparts, often for breaking the rules of community supervision. Risk
      assessments and risk management strategies employed by probation officers can
      lead to higher rates of returns to custody for probationers with mental disorder,
      and the current study is the first to examine these experimentally. Here, 234
      probation officers provided risk assessments and risk management decisions based
      on a vignette portraying a probationer with mental disorder, substance abuse
      disorder, both, or neither. Although substance abuse is a relatively stronger
      risk factor than mental disorder, mental disorder had a stronger effect on
      officers' risk assessments. In terms of risk management, mental disorder had the
      strongest effect on officers' desire to manage risk with forced mental health
      treatment. These findings suggest that training for probation officers in the
      relative utility of mental disorder in predicting risk, in addition to evidence
      based risk management strategies that take the focus off mental disorder, may
      improve outcomes for probationers with mental disorder.

PMID- 22468761
TI  - Failure-to-register laws and public safety: an examination of risk factors and
      sex offense recidivism.
AB  - The goals of this study were to describe the characteristics of a sample of sex
      offenders charged with failure to register (FTR) in New York State, compare the
      FTR and non-FTR groups on relevant risk factors, identify risk factors associated
      with failing to register, and investigate the relationship between registration
      noncompliance and both general and sexual rearrest. FTR offenders were found to
      be younger, more likely to be a minority race, and have more extensive and varied
      prior criminal histories as well as a record of supervision violations. Results
      also indicated that FTR was more strongly correlated with nonsexual recidivism (r
      = .44) than sexual recidivism (r = .09). FTR contributed to the likelihood of
      sexual recidivism for rapists of adult victims, but not for sex offenders with
      child victims, and occurred in combination with a history of prior sexual crimes
      and versatility in criminal offending.

PMID- 22468762
TI  - Association and interaction of -58C>T and +/-9 bp polymorphisms of BDKRB2 gene
      causing susceptibility to essential hypertension.
AB  - INTRODUCTION: Bradykinin, a vasodilator by nature has been documented to have a
      protective role against hypertension and cardiovascular complications.
      Polymorphisms of bradykinin B2 receptor (BDKRB2) gene are reported to be
      predisposing factors for hypertension. Evaluation of the association between 
      58C>T and +/-9 bp polymorphisms of BDKRB2 with essential hypertension (EHT) was
      attempted. METHODS: Two hundred and fourteen primary hypertensives and 249
      controls were genotyped for the selected markers by polymerase chain reaction,
      gel electrophoresis (+/-9 bp), and SSCP (-58C>T). RESULTS: While -58C>T
      polymorphism did not reveal any association with EHT, +/-9 bp polymorphism showed
      a significant association with high risk for heterozygotes (+9/-9) when tested
      against the pooled frequencies of homozygotes (OR [odds ratio] = 1.63, 95%
      confidence interval [CI] = 1.12-2.38, P = .02), and this risk was 1.7 folds high
      in males (OR = 1.74, 95% CI = 1.05-2.86, P = .06) and 1.9 folds high in familial
      cases (OR = 1.96, 95% CI = 1.09-3.53, P = .04). In contrast, significant
      protective effect was observed for -9/-9 genotype against EHT when tested under
      dominant model in general (OR = 0.59, 95% CI = 0.41-0.86, P = .01), in males (OR
      = 0.49, 95% CI = 0.30-0.82, P = .01), and in familial cases (OR = 0.50, 95% CI =
      0.28-0.89, P = .04). Significant risk for +9 bp allele was observed in general
      (OR = 1.39, 95% CI = 1.05-1.86, P = .04) and in males (OR = 1.65, 95% CI = 1.13
      2.41, P = .02). The interaction information analysis revealed a synergistic
      effect between the two polymorphisms contributing to EHT. +9/+9 genotype of +/-9
      bp polymorphism when present in combination with CC genotype of -58C>T
      polymorphism showed 2.2-fold higher risk for developing EHT. CONCLUSIONS: The
      results suggest that allele +9 bp might be a risk factor for EHT in general and
      specially in males. Markers -58C>T and +/-9 bp may act synergistically causing
      susceptibility to EHT.

PMID- 22468763
TI  - Hidden violence is silent rape: sexual and gender-based violence in refugees,
      asylum seekers and undocumented migrants in Belgium and the Netherlands.
AB  - Although women, young people and refugees are vulnerable to sexual and gender
      based violence (SGBV) worldwide, little evidence exists concerning SGBV against
      refugees in Europe. Using community-based participatory research, 223 in-depth
      interviews were conducted with refugees, asylum seekers and undocumented migrants
      in Belgium and the Netherlands. Responses were analysed using framework analysis.
      The majority of the respondents were either personally victimised or knew of a
      close peer being victimised since their arrival in the European Union. A total of
      332 experiences of SGBV were reported, mostly afflicted on them by (ex-)partners
      or asylum professionals. More than half of the reported violent experiences
      comprised sexual violence, including rape and sexual exploitation. Results
      suggest that refugees, asylum seekers and undocumented migrants in Belgium and
      the Netherlands are extremely vulnerable to violence and, specifically, to sexual
      violence. Future SGBV preventive measures should consist of rights-based,
      desirable and participatory interventions, focusing on several socio-ecological
      levels concurrently.

PMID- 22468764
TI  - Young adults with intellectual disability transitioning from school to post
      school: a literature review framed within the ICF.
AB  - PURPOSE: The purpose of this review was to describe literature relating to
      transition for young people with an intellectual disability and identify gaps
      within the current knowledge base. METHOD: A narrative literature review was
      undertaken. Searches of databases Medline, CINAHL, PsycINFO, ERIC, ISI Web of
      Science and ProQuest 500 International provided relevant research articles. The
      search terms used were intellectual disability, transition, employment, and ICF
      as well as other terms derived from the ICF. Manual searches of reference lists
      identified additional studies. Furthermore, government websites were searched for
      relevant reports and policies. RESULTS: Transition literature was explored by ICF
      domains; body functions and structures, activity and participation and contextual
      factors. Studies were identified in some but not all areas and included
      literature describing self-determination and participation in leisure activities
      for those with mild intellectual disability. However, significant gaps were found
      particularly for those with severe intellectual disability. CONCLUSIONS: The ICF
      is a useful tool in framing a review of transition literature for young people
      with intellectual disability due to the complexity and multi-faceted nature of
      transition. The important influence of environmental factors including family
      systems, post-school services and access to transport were highlighted as having
      considerable impacts on transition outcomes.

PMID- 22468765
TI  - Giant vesicles containing superparamagnetic iron oxide as biodegradable cell
      tracking MRI probes.
AB  - A major breakthrough in in vivo cellular imaging has been the
      clinical/preclinical use of magnetic resonance imaging (MRI) with contrast agent.
      Superparamagnetic iron oxide (SPIO) is a promising candidate for the development
      of smart MRI probes for cell-tracking. In the present study, we describe
      biodegradable probes made of giant vesicles (GVs; closed lipid membranes with
      diameters >1 MUm) that encapsulate SPIO for use as an MRI contrast agent. These
      SPIO-containing GVs (SPIO-GVs) exhibited excellent contrast enhancement in the
      single cell of medaka fish (Oryzias latipes) embryos immediately after their
      microinjection, and this enhancement disappeared when the GV membranes were
      destroyed. Our results demonstrate that SPIO-GVs are useful MRI probes for single
      cell-tracking that have minimum cytotoxicity and will greatly improve
      clinical/preclinical in vivo cellular imaging techniques.

PMID- 22468766
TI  - Composite versus single transportable carbohydrate solution enhances race and
      laboratory cycling performance.
AB  - When ingested at high rates (1.8-2.4 g.min(-1)) in concentrated solutions,
      carbohydrates absorbed by multiple (e.g., fructose and glucose) vs. single
      intestinal transporters can increase exogenous carbohydrate oxidation and
      endurance performance, but their effect when ingested at lower, more realistic,
      rates during intermittent high-intensity endurance competition and trials is
      unknown. Trained cyclists participated in two independent randomized crossover
      investigations comprising mountain-bike races (average 141 min; n = 10) and
      laboratory trials (94-min high-intensity intervals followed by 10 maximal
      sprints; n = 16). Solutions ingested during exercise contained electrolytes and
      fructose + maltodextrin or glucose + maltodextrin in 1:2 ratio ingested, on
      average, at 1.2 g carbohydrate.kg(-1).h(-1). Exertion, muscle fatigue, and
      gastrointestinal discomfort were recorded. Data were analysed using mixed models
      with gastrointestinal discomfort as a mechanism covariate; inferences were made
      against substantiveness thresholds (1.2% for performance) and standardized
      difference. The fructose-maltodextrin solution substantially reduced race time (
      1.8%; 90% confidence interval = +/-1.8%) and abdominal cramps (-8.1 on a 0-100
      scale; +/-6.6). After accounting for gastrointestinal discomfort, the effect of
      the fructose-maltodextrin solution on lap time was reduced (-1.1%; +/-2.4%),
      suggesting that gastrointestinal discomfort explained part of the effect of
      fructose-maltodextrin on performance. In the laboratory, mean sprint power was
      enhanced (1.4%; +/-0.8%) with fructose-maltodextrin, but the effect on peak power
      was unclear (0.7%; +/-1.5%). Adjusting out gastrointestinal discomfort augmented
      the fructose-maltodextrin effect on mean (2.6%; +/-1.9%) and peak (2.5%; +/-3.0%)
      power. Ingestion of multiple transportable vs. single transportable carbohydrates
      enhanced mountain-bike race and high-intensity laboratory cycling performance,
      with inconsistent but not irreconcilable effects of gut discomfort as a possible
      mediating mechanism.

PMID- 22468767
TI  - Switching and backward inhibition in major depressive disorder: the role of
      rumination.
AB  - Previous studies have demonstrated that individuals with major depressive
      disorder have difficulties switching attention from one task set to another. In
      the current study we examined whether ruminative thinking drives the switching
      deficits of depressed individuals. A secondary, more exploratory, goal of this
      study was to examine whether state rumination would impair depressed individuals'
      ability to activate a new task set, to inhibit a no longer relevant task set, or
      both. Participants underwent either a rumination induction or a distraction
      induction and then completed a backward inhibition task that measures general
      switching abilities and the ability to inhibit previous task sets. Although
      depression was not related to switching ability as a main effect, depressed
      individuals who were induced to ruminate exhibited poorer switching ability than
      did both depressed and control individuals who were distracted from ruminating
      and control participants who were induced to ruminate. These findings suggest
      that depressed individuals are characterized by switching deficits only if they
      are ruminating. Moreover, the finding that state rumination did not affect
      participants' ability to inhibit previous task sets suggests that state
      rumination primarily impairs noninhibitory task-switching processes. It is
      interesting that the opposite pattern of results was obtained for trait
      rumination, which was related to inhibitory deficits during switching, but not to
      generally poorer switching. Thus, state and trait rumination may be associated
      with dissociable cognitive deficits.

PMID- 22468769
TI  - Early identification of dying trajectories in emergency department patients:
      potential impact on hospital care.

PMID- 22468768
TI  - Solution nuclear magnetic resonance analyses of the anticodon arms of
      proteinogenic and nonproteinogenic tRNA(Gly).
AB  - Although the fate of most tRNA molecules in the cell is aminoacylation and
      delivery to the ribosome, some tRNAs are destined to fulfill other functional
      roles. In addition to their central role in translation, tRNA molecules
      participate in processes such as regulation of gene expression, bacterial cell
      wall biosynthesis, viral replication, antibiotic biosynthesis, and suppression of
      alternative splicing. In bacteria, glycyl-tRNA molecules with anticodon sequences
      GCC and UCC exhibit multiple extratranslational functions, including
      transcriptional regulation and cell wall biosynthesis. We have determined the
      high-resolution structures of three glycyl-tRNA anticodon arms with anticodon
      sequences GCC and UCC. Two of the tRNA molecules are proteinogenic (tRNA(Gly,GCC)
      and tRNA(Gly,UCC)), and the third is nonproteinogenic (np-tRNA(Gly,UCC)) and
      participates in cell wall biosynthesis. The UV-monitored thermal melting curves
      show that the anticodon arm of tRNA(Gly,UCC) with a loop-closing C-A(+) base pair
      melts at a temperature 10  degrees C lower than those of tRNA(Gly,GCC) and np
      tRNA(Gly,UCC). U-A and C-G pairs close the loops of the latter two molecules and
      enhance stem stability. Mg(2+) stabilizes the tRNA(Gly,UCC) anticodon arm and
      reduces the T(m) differential. The structures of the three tRNA(Gly) anticodon
      arms exhibit small differences among one another, but none of them form the
      classical U-turn motif. The anticodon loop of tRNA(Gly,GCC) becomes more dynamic
      and disordered in the presence of multivalent cations, whereas metal ion
      coordination in the anticodon loops of tRNA(Gly,UCC) and np-tRNA(Gly,UCC)
      establishes conformational homogeneity. The conformational similarity of the
      molecules is greater than their functional differences might suggest. Because
      aminoacylation of full-length tRNA molecules is accomplished by one tRNA
      synthetase, the similar structural context of the loop may facilitate efficient
      recognition of each of the anticodon sequences.

PMID- 22468770
TI  - End-of-life decision-making confidence in surrogates of African-American dialysis
      patients is overly optimistic.
AB  - BACKGROUND: Recent studies suggest that surrogate decision makers may be too
      optimistic about their end-of-life decision making abilities for loved ones. We
      examined surrogates' decision making confidence with an emphasis on its linkages
      to their understandings of patients' values and goals for end-of-life care.
      METHODS: We used baseline data from a randomized trial with 58 dyads of African
      American dialysis patients and their surrogates who separately completed the
      Values of Life-Sustaining Treatment Outcomes and the Goals of Care documents.
      Surrogates also completed a Surrogate Decision Making Confidence Scale. RESULTS:
      Overall, 60% of surrogates were unsure how their loved ones would feel about
      continuing life-sustaining treatment, including dialysis, in at least one of the
      four outcomes presented in the Values of Life-Sustaining Treatment Outcomes. For
      goals of care near end of life, 67.2% to 69.0% of patients preferred comfort care
      only, but only 20 (34.5%) surrogates were congruent with patients on Goals of
      Care. Nonetheless, surrogates' confidence was high (M=3.23 out of 4.0).
      Surrogates' confidence was positively associated with dyad congruence in values
      for life-sustaining treatment at only a small magnitude (Spearman's rho=.31,
      p=.02), but not with dyad congruence in goals of care (chi(2)=2.13, df=1, p=.19).
      CONCLUSIONS: Surrogates' confidence had little association with their actual
      understanding of patients' values and goals. Interventions to prepare patients
      and surrogates for end-of-life decision making may need to address overconfidence
      and help surrogates recognize their limited understanding of patients' values and
      goals.

PMID- 22468771
TI  - Characteristics of emergency department patients who receive a palliative care
      consultation.
AB  - BACKGROUND: A large gap exists between the practice of emergency medicine and
      palliative care. Although hospice and palliative medicine has recently been
      recognized as a subspecialty of emergency medicine, few palliative care teams
      routinely interact with emergency providers, and primary palliative care skills
      among emergency providers are lacking. OBJECTIVE: To identify the proportion and
      characteristics of patients who receive a palliative care consultation and arrive
      via the emergency department (ED). METHODS: A descriptive study of adult ED
      patients from an urban, academic tertiary care hospital who received a palliative
      care consultation in January 2005 or January 2009. RESULTS: In January 2005, 100
      of the 161 consults (62%) arrived via the ED versus 63 of 124 consults (51%) in
      January 2009 (p=0.06). Mean days from admission to consultation in January 2005
      were six days (standard deviation 11), versus nine days (SD 26) in January 2009
      (p=0.35). Three of the 100 consultations (3%) in January 2005 were initiated in
      the ED, versus 4 of the 64 (6%) in January 2009. CONCLUSIONS: At an urban
      academic medical center with a well-developed palliative care service, the
      majority of palliative care consultations were for patients who arrive via the
      ED. Despite this, only a small minority of consultations originated from
      emergency providers and consultation was on average initiated days into a
      patient's hospital stay.

PMID- 22468772
TI  - Mood and pain responses to repeat dose intramuscular ketamine in a depressed
      patient with advanced cancer.
AB  - Depression is highly prevalent in patients with advanced cancer, commonly
      affecting quality of life. Considering the response delay with conventional
      antidepressants and the short life expectancy for these patients, treatments for
      Major Depressive Disorder (MDD) with faster onset of action are desirable. In
      this case report, a female patient with metastatic ovarian cancer presented rapid
      and sustained response to intramuscular (IM) injections of ketamine (1mg/kg).
      Over a course of six treatments, her mood response was identical on each occasion
      and provided remission of her depressive symptoms. Pain was also improved,
      although for a shorter duration. These findings support the use of IM ketamine as
      a possible antidepressant option for this population.

PMID- 22468773
TI  - Barriers to end-of-life care in the intensive care unit: perceptions vary by
      level of training, discipline, and institution.
AB  - PURPOSE: Barriers to providing quality end-of-life (EOL) care in the intensive
      care unit (ICU) are common, but little is known about how these barriers vary by
      level of training or discipline. METHODS: Medical residents and ICU fellows,
      attendings, and nurses at two teaching hospitals were surveyed about barriers to
      EOL care in the ICU. The survey consisted of questions about possible barriers in
      four domains: patient-family factors, clinician factors, institutional factors,
      and education-training factors. RESULTS: There were significant differences in
      reported barriers to EOL care by level of training, discipline, and institution,
      particularly in the education-training domain. Insufficient resident training in
      EOL care was reported as a large or huge barrier by a smaller proportion of
      residents (20%) than attendings (62%), fellows (55%) or nurses (36%) (p=0.001).
      Nurses' perceptions of barriers to EOL care varied between institutions. Barriers
      that varied significantly between nurses included difficulty communicating due to
      language (p=0.008), and inadequate training in recognition of pain and anxiety
      (p=0.001). CONCLUSIONS: We found that perceived barriers to EOL care differed
      significantly by level of training, discipline and institution, suggesting the
      interventions to improve EOL care may need to be locally targeted and specific to
      level of training and discipline.

PMID- 22468774
TI  - yaInChI: modified InChI string scheme for line notation of chemical structures.
AB  - A modified InChI (International Chemical Identifier) string scheme, yaInChI (yet
      another InChI), is suggested as a method for including the structural information
      of a given molecule, making it straightforward and more easily readable. The
      yaInChI theme is applicable for checking the structural identity with higher
      sensitivity and generating three-dimensional (3-D) structures from the one
      dimensional (1-D) string with less ambiguity than the general InChI method. The
      modifications to yaInChI provide non-rotatable single bonds, stereochemistry of
      organometallic compounds, allene and cumulene, and parity of atoms with a lone
      pair. Additionally, yaInChI better preserves the original information of the
      given input file (SDF) using the protonation information, hydrogen count +1, and
      original bond type, which are not considered or restrictively considered in InChI
      and SMILES. When yaInChI is used to perform a duplication check on a 3D chemical
      structure database, Ligand.Info, it shows more discriminating power than InChI.
      The structural information provided by yaInChI is in a compact format, making it
      a promising solution for handling large chemical structure databases.

PMID- 22468775
TI  - Cation-induced synthesis of new polyoxopalladates.
AB  - Seven polyoxopalladate compounds, [Pd(15)(SeO(3))(10)(MU(3)-O)(10)](10-), with
      Na(+) (1) and K(+) (2) as counterions, and Na(6)[M(II){Pd(12)(SeO(3))(8)(MU(4)
      O)(8)}].nH(2)O (M = Co (3), Zn (4), Ni (5), Cu (6), Mn (7); n = 7-9), have been
      prepared and characterized by SXRD, FT-IR, UV-vis, EA, TGA, and ESI-MS. These
      compounds comprise two distinct cluster configurations, {Pd(15)} and
      {M(II)Pd(12)}, which reveals the possibility of obtaining desired noble metal
      clusters with a certain nuclearity by using different cations as potential
      structural directing or template agents in synthesis. All compounds showed
      apparent absorptions in the visible light region, while 3 and 7 were found to
      show paramagnetic behavior typical of mononuclear Co(II) and Mn(II) complexes
      with zero-field splitting.

PMID- 22468776
TI  - Mesoporous and macroporous brookite thin films having a large thermal stability
      range.
AB  - A sol-gel chemistry approach is employed to generate mesoporous and macroporous
      brookite thin films using Ag ions as dopant species whose thermal stability is
      well above previously reported literature values for thin films. The Ag ions not
      only induce the formation of brookite but also participate in its enhanced
      thermal stability. Despite brookite being metastable in nature, which renders it
      a challenge to synthesize, it has been prescribed as a potential competitor to
      anatase. We have used a layer-by-layer approach to generate a mesoporous Ag-doped
      brookite structure at 500  degrees C with 95% composition by XRD. This tightly
      packed mesoporous structure can be described as striated grains of brookite
      protruding from the surface to form an interlocked network whose thermal
      stability spans up to 800  degrees C. The open structure of brookite makes it an
      apt host for the intercalant Ag species, whose inclusion within the brookite
      framework is improved by the presence of a stabilizing agent. Both the morphology
      of the surface and the presence of a stabilization agent for Ag contribute to
      enhancing its thermal stability. This is in contrast to the thermal stability of
      the macroporous brookite thin film, which was found to be lower (<700  degrees C)
      than that of the mesoporous brookite thin film. The reagents are deliberately
      chosen to produce a macroporous film in the absence of a stabilizing agent. Ag
      nodules are observed to be formed at 700  degrees C, which implies their limited
      intercalation into the brookite structure, thus rendering them relatively less
      stable. Moreover, the macroporous film being relatively more relaxed is more
      susceptible to phase transformation at a higher calcination temperature. Our
      results provide a platform that paves the way toward better control, thereby
      leading to a broader technological application of brookite. 

PMID- 22468777
TI  - Entropy-controlled 2D supramolecular structures of N,N'-bis(n
      alkyl)naphthalenediimides on a HOPG surface.
AB  - The two-dimensional supramolecular structures of a series of N,N'-bis(n
      alkyl)naphthalenediimides (NDIs), whose chain lengths span from C3 to C18, at a
      liquid-HOPG surface interface, studied by STM and FM-AFM, are assigned with the
      help of molecular dynamics/molecular mechanics calculations to demonstrate that
      the C3- and C4-NDIs show lamellar structures, the C4- to C12-NDIs show honeycomb
      (KAGOME) structures, and the C14- to C18-NDIs show lamellar structures again. The
      change in supramolecular structure depending on chain length can be explained
      semiquantitatively by the balance of entropy and enthalpy terms to show the
      importance of "self-avoiding walk" of the alkyl chain in entropy terms.

PMID- 22468778
TI  - Arsenic trioxide  for management of acute promyelocytic leukemia: current
      evidence on its role in front-line therapy and recurrent disease.
AB  - INTRODUCTION: Acute promyelocytic leukemia (APL), the most rapidly fatal leukemia
      only two decades ago, has been converted into the most frequently curable
      leukemia by the advent of all-trans retinoic acid (ATRA) and its combination with
      anthracycline-based chemotherapy. More recently, arsenic trioxide (ATO) has been
      shown to be the most effective single agent in this disease and has been approved
      for the treatment of relapsed patients both in the United States and Europe.
      Moreover, ATO has been included in the design of several front-line studies, with
      the aim to reduce therapy-related toxicity while maintaining the potential of
      cure. AREAS COVERED: First, this review briefly discusses the mechanisms of
      action and the toxicity profile of ATO. Furthermore, the reported experience on
      the use of ATO as single agent or in combinatorial schemes both in relapsed and
      in newly diagnosed patients with APL is critically reviewed. Finally, the use of
      this agent in special subsets of patients unfit to receive conventional
      chemotherapy is discussed, along with its potential role in maintenance therapy.
      EXPERT OPINION: While the role of ATO as single agent or in combination with ATRA
      is well established and recommended by the European LeukemiaNet guidelines as a
      first option for relapsed patients, the role of the drug in newly diagnosed
      patients is still uncertain and based only on evidence levels mostly originating
      from non-randomized trials. The results of ongoing randomized studies should
      better define the role of ATO in front-line therapy.

PMID- 22468779
TI  - Controlled dissolution of polystyrene nanobeads: transition from liquid
      electrolyte to gel electrolyte.
AB  - The widespread commercialization of dye-sensitized solar cells (DSSCs) remains
      limited because of the use of highly volatile liquid electrolytes. Recently, gel
      type quasi-solid electrolytes containing a polymer additive or inorganic
      nanomaterial have shown promising results in terms of the cell efficiency.
      However, most gel electrolytes have serious obstacles for pore-filling because of
      their high viscosity. Herein, we report the first observation of the transition
      from a liquid to a gel electrolyte after filling the cell with the liquid
      electrolyte using the controlled dissolution of polystyrene nanobeads on the
      counter electrode, suggesting that the pore-filling problem can be diminished in
      quasi-solid state DSSCs. The time-resolved solidification allows for the
      preparation of the gel electrolyte without interfering with the cell performance.
      The optimal DSSC composed of the gel electrolyte exhibits almost the same power
      conversion efficiency as the liquid electrolyte based DSSC when measured using an
      AM1.5G solar simulator at 100 mW/cm(2) light illumination. Moreover, the long
      term stability of the DSSC was greatly improved.

PMID- 22468780
TI  - Tumor cell expression of heat shock protein (HSP) 72 is influenced by HSP72
      [HSPA1B A(1267)G] polymorphism and predicts survival in small Cell lung cancer
      (SCLC) patients.
AB  - The inducible heat shock protein (HSP)72 plays a central role in antitumor
      immunomodulation. HSP72 expression was assessed on tumor samples of 43 patients
      with advanced and metastatic small cell lung cancer (SCLC) by
      immunohistochemistry and HSP72 [HSPA1B A(1267)G] polymorphism was determined.
      HSP72 expression of SCLC cells was significantly decreased in GG as compared to
      cells of AA or AG genotype patients, and was associated with significantly
      shorter survival in GG patients as compared to carriers of the A allele.
      Decreased HSP72 expression of SCLC cells associated with HSP72 GG genotype is a
      negative prognostic factor for survival in SCLC patients.

PMID- 22468781
TI  - Influence of substrate wettability on the morphology of thin polymer films spin
      coated on topographically patterned substrates.
AB  - We show that the morphology of a thin polymer film spin coated directly on to a
      topographically patterned substrate is strongly influenced by the wettability of
      the substrate, in addition to other well-known parameters such as concentration
      of the polymer solution (c(n)), spin speed (RPM), and spin duration. Similar to
      spin coating on a flat surface, (1, 2)  on a topographically patterned substrate
      as well, a continuous film forms only above a critical polymer solution
      concentration (c(t)*), for a specific RPM and dispensed drop volume. It is
      believed that for c(n) > c(t)*, the resulting continuous film on a
      topographically patterned substrate has an undulating top surface, where the
      surface undulations are in phase with the underlying substrate patterns. (3)  On
      the basis of experiments involving spin coating of polymer thin films on
      topographically patterned grating substrates, we show that the surface
      undulations on the film are in phase with the substrate patterns only when the
      substrate is completely wetted (CW) by the solvent. In contrast, when the
      substrate is partially wetted (PW) by the solvent, then the undulations are 180
      degrees  out of phase with respect to the substrate patterns. We further show
      that for c(n) < c(t)*, a variety of ordered and disordered structures, like array
      of aligned droplets, isolated strips of polymers, etc., result on both CW and PW
      substrates, depending on c(n).

PMID- 22468782
TI  - Improve the coverage for the analysis of phosphoproteome of HeLa cells by a
      tandem digestion approach.
AB  - Complete coverage of all phosphorylation sites in a proteome is the ultimate goal
      for large-scale phosphoproteome analysis. However, only making use of one
      protease trypsin for protein digestion cannot cover all phosphorylation sites,
      because not all tryptic phosphopeptides are detectable in MS. To further increase
      the phosphoproteomics coverage of HeLa cells, we proposed a tandem digestion
      approach by using two different proteases. By combining the data set of the first
      Glu-C digestion and the second trypsin digestion, the tandem digestion approach
      resulted in the identification of 8062 unique phosphopeptides and 8507
      phosphorylation sites in HeLa cells. The conventional trypsin digestion approach
      resulted in the identification of 3891 unique phosphopeptides and 4647
      phosphorylation sites. It was found that the phosphorylation sites identified
      from the above two approaches were highly complementary. By combining above two
      data sets, in total we identified 10899 unique phosphopeptides and 11262
      phosphorylation sites, corresponding to 3437 unique phosphoproteins with FDR < 1%
      at peptide level. We also compared the kinase motifs extracted from trypsin, Glu
      C, or a second trypsin digestion data sets. It was observed that basophilic
      motifs were more frequently found in the trypsin and the second trypsin digestion
      data sets, and the acidic motifs were more frequently found in the Glu-C
      digestion data set. These results demonstrated that our tandem digestion approach
      is a good complement to the conventional trypsin digestion approach for improving
      the phosphoproteomics analysis coverage of HeLa cells.

PMID- 22468783
TI  - Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of
      cognitive function induced by injection of beta-amyloid in rats.
AB  - CONTEXT: Chamaecyparis obtusa Sieb. & Zucc., Endlicher (Cupressaceae) forest
      bathing or aromatherapy has been shown in various studies to have biological
      functions such as anticancer, antiallergies, antiinflammatory, and antioxidant
      activity. However, no reports exist on the pharmacological or biological
      activities of the essential oil of C. obtusa (EOCO) or its effects on central
      nervous system. OBJECTIVE: The aggregation and formation of beta-amyloid peptides
      (Abeta) into fibrils are central events in the pathogenesis of Alzheimer's
      disease (AD), and overproduction and aggregation of Abeta into oligomers have
      been known to trigger neurotoxicity. In this study, we investigated the effects
      of inhaled EOCO on cognitive function and neuronal apoptosis in rats
      intrahippocampally injected with Abeta. MATERIALS AND METHODS: To model AD, 4 MUg
      of aggregated Abeta was injected into the hippocampus. To test the effects of
      EOCO, behavioral performance in the Morris water maze was tested 4 days after
      injection. After behavioral testing, brain sections were prepared for TTC
      staining and TUNEL assay. RESULTS: Inhaled EOCO protected spatial learning and
      memory from the impairments induced by Abeta(1-40) injection. In addition, the
      behavioral deficits accompanying Abeta(1-40)-induced AD were attenuated by
      inhalation of EOCO. Furthermore, acetylcholinesterase (AChE) activity and
      neuronal apoptosis were significantly inhibited in rats treated with Abeta(1-40)
      and EOCO compared to rats treated only with Abeta(1-40). DISCUSSION AND
      CONCLUSION: EOCO suppressed both AD-related neuronal cell apoptosis and AD
      related dysfunction of the memory system. Thus, the results of this study support
      EOCO as a candidate drug for the treatment of AD.

PMID- 22468784
TI  - Reactions of neutral gas-phase yttrium atoms with two cyclohexadiene isomers.
AB  - The reactions of neutral ground-state yttrium (Y) atoms with 1,3- and 1,4
      cyclohexadiene (CHD) were studied using crossed molecular beams. Formation of
      YC(6)H(6) + H(2) and YH(2) + C(6)H(6) was observed for both isomers at collision
      energies (E(coll)) of 31.3 and 13.0 kcal/mol. Measured product branching ratios
      at E(coll) = 31.3 kcal/mol indicated that YH(2) + C(6)H(6) was the dominant
      channel, accounting for >97% of the products. An additional minor product
      channel, YC(4)H(4) + C(2)H(4), was observed for 1,3-CHD at the higher E(coll).
      The reaction threshold for YC(4)H(4) formation was determined to be 29.5 +/- 2.0
      kcal/mol based on fits to the data.

PMID- 22468785
TI  - Healthy marriage initiatives: on the need for empiricism in policy
      implementation.
AB  - The association between marriage and well-being has led to policies that promote
      marital interventions and discourage divorce. These include federal initiatives
      specifically targeting poor couples and couples of color. While there are many
      prospective studies on marriage that have informed some couple interventions, the
      studies that are included in this literature sampled predominantly White and
      middle-class couples. By comparison, far less is known about the longitudinal
      predictors of relationship satisfaction and status for poor couples and couples
      of color. Therefore, it is unsurprising that preliminary data on applying current
      interventions to the couples targeted by these federal initiatives have been
      disappointing. In this article, I detail three concerns with these initiatives,
      propose a course of psychological research to address deficits in what is known
      about poor couples and couples of color, and make specific recommendations to
      enhance the effectiveness of these initiatives.

PMID- 22468786
TI  - Norine G. Johnson (1935-2011).
AB  - On November 19, 2011, Norine G. Johnson, the ninth woman to serve as president of
      the American Psychological Association (APA), lost a valiant battle with cancer.
      Norine's curiosity about her grandmother's strength led to much of her later work
      on the development of strength and resiliency in adolescent girls and in women.
      She received her doctorate in 1972, with a minor in child development, and she
      became one of the first to be considered a pediatric psychologist, a newly
      emerging specialty. Norine became involved in organized psychology as her
      children got older. When she learned there had not been a woman president of the
      Massachusetts Psychological Association (MPA) for almost 50 years, she was
      appalled. An ardent feminist, who had served on MPA's Board of Directors, she
      could not let the situation remain that way. She ran for president and won,
      serving from 1981 to 1983, and then mentored many women colleagues into the role.
      MPA sent her to the Council of the APA as one of their representatives, and she
      immediately ran for a seat on the Finance Committee, later serving as chair of
      the committee. During her tenure on the Finance Committee, she helped create
      financial policy that changed APA from an organization whose assets were
      threatened and shrinking to a financially solid association. Norine considered
      Division 35 (Psychology of Women) to be her home in APA, a place filled with
      warmth, collegiality, and shared values. She and Judith Worell spearheaded the
      extremely important and successful 1993 National Conference on Education and
      Training in Feminist Practice. Norine was elected to the APA Board of Directors
      in 1997, where she served with distinction, continuing to focus on the financial
      well-being of the Association. Not surprisingly, she went from that role to being
      elected APA president. Her focus as president was on the changes in the health
      care delivery system in the United States. She was a staunch champion of the
      biopsychosocial model of health. Under her presidential leadership, the APA
      Mission Statement was amended to add the word "health," confirming the importance
      of health to the psychological community. (PsycINFO Database Record (c) 2012 APA,
      all rights reserved).

PMID- 22468787
TI  - Morris B. Parloff (1918-2011).
AB  - Morris B. Parloff was considered an elder statesman in the field of psychotherapy
      research, and his wisdom and stewardship were of enormous benefit to several
      generations of psychotherapy researchers. Parloff received his bachelor's degree
      from Western Reserve University (1940), a degree in psychiatric social work from
      the University of Chicago (1942), and a doctorate in psychology from Western
      Reserve University (1953). Parloff spent most of his career (from 1953 until his
      retirement in 1983) as a researcher and administrator at the National Institute
      of Mental Health (NIMH). He was also on the senior faculty of the Washington
      School of Psychiatry, taught or consulted at a number of universities, and
      maintained a private practice of psychotherapy. In the NIMH intramural program,
      Parloff was chief of the Section on Personality in the Laboratory of Psychology.
      There he conducted a major longitudinal study on the personality characteristics
      of adolescent and adult scientists. In the NIMH extramural program, he served as
      chief of the Psychotherapy and Behavioral Intervention Section in the Clinical
      Research Branch (1972-1980), after which he became chief of the new Psychosocial
      Treatments Research Branch. Throughout his career, from his pioneering teaching
      and research on group psychotherapy through his 30 years at NIMH, Parloff
      provided researchers and practitioners with a broad understanding of the field of
      psychotherapy research, the complexity of its subject matter, and its
      relationship to the "real world." Often ahead of others in the field, Parloff
      dealt with many topics that retain their importance today, including the need to
      carefully define criteria for improvement in psychotherapy, the transmission of
      values in psychotherapy, the concepts of the placebo and of common factors in
      psychotherapy research, and the role of the patient-therapist relationship (in
      both individual and group therapy) and its impact on the outcome of therapy.
      Starting with a 1979 article in the American Psychologist ("Can Psychotherapy
      Research Guide the Policymaker? Vol. 34, pp. 296-306), Parloff wrote extensively
      about the relationship among practitioners, psychotherapy researchers, and
      policymakers. To promote the systematic use of clinical trials and address
      methodological issues in the field, Parloff obtained support to fund the first
      NIMH multisite collaborative outcome study in the field of psychotherapy. He and
      the first author (I. E.) then designed and launched the NIMH Treatment of
      Depression Collaborative Research Program. This study would serve as a model for
      future collaborative research by independent investigators. (PsycINFO Database
      Record (c) 2012 APA, all rights reserved).

PMID- 22468788
TI  - FT-IR spectroscopic imaging of reactions in multiphase flow in microfluidic
      channels.
AB  - Rapid, in situ, and label-free chemical analysis in microfluidic devices is
      highly desirable. FT-IR spectroscopic imaging has previously been shown to be a
      powerful tool to visualize the distribution of different chemicals in flows in a
      microfluidic device at near video rate imaging speed without tracers or dyes.
      This paper demonstrates the possibility of using this imaging technology to
      capture the chemical information of all reactants and products at different
      points in time and space in a two-phase system. Differences in the rates of
      chemical reactions in laminar flow and segmented flow systems are also compared.
      Neutralization of benzoic acid in decanol with disodium phosphate in water has
      been used as the model reaction. Quantitative information, such as concentration
      profiles of reactant and products, can be extracted from the imaging data. The
      same feed flow rate was used in both the laminar flow and segmented flow systems.
      The laminar flow pattern was achieved using a plain wide T-junction, whereas the
      segmented flow was achieved by introducing a narrowed section and a nozzle at the
      T-junction. The results show that the reaction rate is limited by diffusion and
      is much slower with the laminar flow pattern, whereas the reaction is completed
      more quickly in the segmented flow due to better mixing.

PMID- 22468789
TI  - Prevalence, self-awareness, treatment, and control of hypertension in Lhasa,
      Tibet.
AB  - To investigate the prevalence, self-awareness, and treatment of hypertension in
      Lhasa, Tibet, a total of 1370 native Tibetan aged >=18 years were selected, using
      stratified proportional sampling. The study showed that the prevalence of
      hypertension was 51.2%, significantly higher in men (56.0%) than in women (48.0%)
      (P = .004). The hypertension prevalence increased with increasing age (77.8% in
      60-74 y and 82.5% in >=75 y groups) and was higher in urban, suburban, or
      agricultural area than in pastoral area (P < .001). The self-awareness,
      treatment, and control rate of hypertension were 63.5%, 24.3% and 7.7%,
      respectively. In multivariable regression analysis, age, urban residence, amount
      of daily intake of fat and oil, and body mass index <18.5 kg/m(2) were
      independently associated with hypertension. In conclusion, hypertension was
      highly prevalent among native Tibetan people in Lhasa, and the rates of self
      awareness, treatment, and control of hypertension were low.

PMID- 22468790
TI  - Lower use of sexual and reproductive health services among women with frequent
      religious participation, regardless of sexual experience.
AB  - PURPOSE: To investigate associations between religious characteristics and sexual
      and reproductive health (SRH) service use among young women in the United States.
      METHODS: We combined two cycles of data from the U.S. population-based
      reproductive health survey, The National Survey of Family Growth (2002 and 2006
      2008). Our analysis was restricted to young women aged 15-24 years (n=4421). We
      tested relationships between religious characteristics, including religious
      affiliation, service participation, and importance of religion in daily life, and
      use of SRH services for contraception, sexually transmitted infection (STI)
      testing/treatment, and routine gynecologic examination care within the last year.
      RESULTS: Nearly all young women identified a current religious affiliation (82%),
      with 46% identifying Protestant and 28% Catholic. Three quarters (75%) of young
      women reported current religious service participation, the majority of whom had
      experienced sexual intercourse (70%); 31% reported weekly religious service
      participation. Over half (59%) had used SRH services recently. In unadjusted
      analyses, young women with current religious affiliation who participated in
      services weekly and deemed religion important had lower proportions of SRH
      service use than their counterparts (all p<0.001). In multivariate regression
      models, young women with less-than-weekly religious service participation were
      50% more likely to use services than those participating weekly (odds ratio [OR]
      1.5, confidence interval [CI] 1.3, 2.1, p<0.001), even among sexually experienced
      women. CONCLUSIONS: Increasing frequency of current religious service
      participation was negatively associated with SRH service use among young women,
      despite sexual experience. Religiously and sexually active young women in the
      United States may have an unmet need for SRH care.

PMID- 22468791
TI  - Association between INS-VNTR polymorphism and polycystic ovary syndrome in a
      Korean population.
AB  - Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive
      ages. But its etiology is not fully understood yet. Variability in the number of
      tandem repeats of the insulin gene (INS-VNTR) is known to associate with PCOS,
      and it is associated with an increased risk of diabetes mellitus and other
      cardiovascular diseases. The aim of our study was to analyze an association
      between the INS-VNTR polymorphism and PCOS in a Korean population. The -23/Hph I
      polymorphism was used as a surrogate marker for INS-VNTR polymorphism and a total
      of 218 PCOS patient and 141 control DNAs were analyzed by restriction fragment
      length polymorphism method. Statistical analysis of genotyping results were
      performed using HapAnalyzer. chi2 test and logistic regression were used to
      analyze the association between two groups. A p value <0.05 was considered
      statistically significant. The frequencies of A/A and A/T genotypes indicated a
      similar change between PCOS patients and controls. In conclusion, there was no
      association between PCOS and INS-VNTR polymorphism (p = 0.0544, odds ratio =
      1.69). Our present data demonstrate that INS-VNTR polymorphism is not related
      with PCOS in Korean women. Thus, it is suggested that INS-VNTR polymorphism is
      not a key factor in the etiology and the pathogenesis of PCOS in a Korean
      population.

PMID- 22468792
TI  - Copper(I) and silver(I) 2-methylimidazolates: extended isomerism, isomerization,
      and host-guest properties.
AB  - Syntheses, structures, and properties of univalent coinage metal 2
      methylimidazolate supramolecular isomers [M(mim)] (1, M = Cu; 2, M = Ag) were
      investigated in detail. In addition to the known isomers, namely, zigzag chains
      [Cu(mim)] (1a) and [Ag(mim)] (2a), molecular octagon [Cu(8)(mim)(8)].C(6)H(6)
      (1b), decagon [Cu(10)(mim)(10)].C(8)H(10) (1c), helical chain
      [Ag(4)(mim)(4)].C(6)H(6) (2b), and S-shaped chain [Ag(4)(mim)(4)].C(8)H(10) (2c),
      two new structures including a polyrotaxane [Cu(10)(mim)(10)].[Cu(mim)] (1d,
      C2/m, a = 14.452(4) A, b = 27.712(7) A, c = 11.427(3) A, beta = 125.899(4)
      degrees , V = 3707(2) A(3)) and a new octagon [Ag(8)(mim)(8)].Me(2)CO (2d, C2/c,
      a = 21.852(3) A, b = 12.101(2) A, c = 20.907(3) A, beta = 90.875(2) degrees , V =
      5528(2) A(3)) were discovered. The potential porous properties of guest
      containing [M(mim)] isomers were studied by thermogravimetry, X-ray powder
      diffraction, vacuum thermal desorption, and CO(2) sorption experiments. The
      isomers show distinctly different guest removal behaviors depending on their pore
      structures. By heating, the guest-containing isomers, 1b-1c and 2b-2d, undergo
      irreversible, two-step, crystal-to-crystal structural transformations to form the
      guest-free isomers 1a or 2a, respectively. Except 1b, other guest-containing
      isomers can retain their porous structures after removal of the template
      molecules, which were confirmed by CO(2) sorption experiments.

PMID- 22468793
TI  - Transsexual emergence: gender variant identities in Thailand.
AB  - This paper aims to contribute to understanding of emergent gender/sexual
      identities in Thailand. Thailand has become a popular destination for sex change
      operations by providing the medical technology for a complete transformation,
      with relatively few procedures and satisfactory results at a reasonable price.
      Data were gathered from 24 transsexual male-to-female sex workers working in
      Pattaya and Patpong, well-known sex-tourism hot spots in Thailand. Findings
      suggest the emergence of new understandings of gender/sexual identity. Sex
      tourism/sex work significantly illuminates the process through which gender is
      contested and re-imagined. The coming together of cultures in Thailand's sex
      industry, coupled with advances in medical technology, has resulted in the
      emergence of new concepts of gender.

PMID- 22468794
TI  - LSD1/CoREST reversible opening-closing dynamics: discovery of a nanoscale clamp
      for chromatin and protein binding.
AB  - LSD1 associated with its corepressor protein CoREST is an exceptionally relevant
      target for epigenetic drugs. Hypotheses for the role of LSD1/CoREST as a
      multidocking site for chromatin and protein binding would require significant
      molecular flexibility, and LSD1/CoREST large-amplitude conformational dynamics is
      currently unknown. Here, molecular dynamics simulation reveals that the
      LSD1/CoREST complex in solution functions as a reversible nanoscale binding
      clamp. We show that the H3 histone tail binding pocket is a potential allosteric
      site for regulation of the rotation of SWIRM/SANT2 domains around the Tower
      domain. Thus, targeting this site and including receptor flexibility are crucial
      strategies for future drug discovery.

PMID- 22468796
TI  - In situ intercalation replacement and selective functionalization of graphene
      nanoribbon stacks.
AB  - A cost-effective and potentially industrially scalable, in situ functionalization
      procedure for preparation of soluble graphene nanoribbon (GNRs) from commercially
      available carbon nanotubes is presented. The physical characteristics of the
      functionalized product were determined using SEM, evolved gas analysis, X-ray
      diffraction, solid-state (13)C NMR, Raman spectroscopy, and GC-MS analytical
      techniques. A relatively high preservation of electrical properties in the bulk
      material was observed. Moreover, replacement of intercalated potassium with
      haloalkanes was obtained. While carbon nanotubes can be covalently
      functionalized, the conversion of the sp(2)-hybridized carbon atoms to sp(3)
      hybridized atoms dramatically lowers their conductivity, but edge functionalized
      GNRs permit their heavy functionalization while leaving the basal planes intact.

PMID- 22468795
TI  - Neuromuscular fatigue recovery following rapid and slow stretch-shortening cycle
      movements.
AB  - The purpose of this study was to investigate underlying mechanisms and
      neuromuscular recovery patterns following rapid and slow stretch-shortening cycle
      (SSC) movements performed to fatigue. Fourteen (10 moderately trained (MT) and
      four highly trained (HT)) subjects completed rapid and slow SSC movements to
      fatigue. The rapid SSC movement consisted of continuous drop jumps from a 30 cm
      platform until a predetermined jump height was no longer maintained, and the slow
      SSC movement consisted of continuous squats to 90 degrees  of knee flexion at a
      load of 65% of subject's one-repetition maximum until no further repetitions
      could be completed. Although blood lactate measures were significantly (p <
      0.002) higher after the rapid SSC condition versus after the slow SSC condition,
      the recovery of neuromuscular properties (maximum voluntary contractions, twitch
      force, muscle compound action potential) following the two conditions to fatigue
      did not differ. The duration of the rapid SSC movement was dependent on the
      training status of the subject; HT subjects performed the rapid SSC longer
      (68.2%) than the MT subjects until fatigued. Thus, the neuromuscular fatigue
      recovery patterns were independent of the type of SSC movement, condition
      duration, and subject training status. Because rapid and slow SSC exercises
      induce similar fatigue patterns, training programs incorporating rapid SSC
      exercises can be developed similar to that prescribed in traditional slow SSC
      resistance training programs.

PMID- 22468797
TI  - Pre-eclampsia-eclampsia admitted to critical care unit.
AB  - OBJECTIVE: To evaluate women with hypertensive disorder admitted to critical care
      unit. METHODS: This study was carried out in Cartagena, Colombia, between January
      2006 and December 2009. Patients were divided into 4 groups; severe pre
      eclampsia, eclampsia, HELLP syndrome and HELLP with eclampsia (HEEH). RESULT: A
      total of 217 cases were admitted. The admitting diagnoses were severe pre
      eclampsia without HELLP syndrome (39.2%), HELLP syndrome without eclampsia
      (33.6%), eclampsia without HELLP syndrome (20.3%) and Eclampsia with HELLP
      syndrome or HEEH (6.9%). Groups were similar with respect to parity (p = 0.25),
      gestational age (p = 0.11), cesarean section (p = 0.58), mechanical ventilation
      (p = 0.54), level of systolic (p = 0.48) and diastolic blood pressure (p = 0.15)
      and inotropic support (p = 0.32). Average total duration of hospitalization was
      significantly different among groups, more time in women with HEEH (p = 0.001).
      Multiple organ dysfunctions was diagnosed > 70% of all women admitted to
      intensive care, but was significantly more frequent in patients with HELLP
      syndrome and HEEH (p = 0.001). There were 5 maternal deaths (2.3%). Causes of
      maternal death were intracranial hemorrhage (3), intra-abdominal bleeding (1) and
      pulmonary complications (1). CONCLUSION: Women with HELLP syndrome with or
      without eclampsia are associated with major morbidity and mortality. Therefore,
      the maternal outcome in eclampsia is influenced for HELLP syndrome.

PMID- 22468798
TI  - Identification of particulate matter sources on an hourly time-scale in a wood
      burning community.
AB  - Particulate matter (PM) sources at two different sites in a rural town in New
      Zealand were investigated on an hourly time-scale. Streaker samplers were used to
      collect hourly, size-segregated PM(10-2.5) and PM(2.5) samples that were analyzed
      for elemental content using ion beam analysis techniques. Black carbon
      concentrations were determined using light reflection and PM(10) concentrations
      were recorded using colocated continuous PM monitors. PM(10) concentrations at
      both sites displayed a diurnal pattern, with hourly PM(10) concentration maxima
      in the evening (7 pm-midnight) and in the morning (7-9 am). One of the monitoring
      sites experienced consistently higher average PM(10) concentrations during every
      hour and analysis indicated that katabatic flows across the urban area
      contributed to the increased concentrations observed. Source apportionment using
      positive matrix factorization on the hourly data revealed four primary PM(10)
      sources for each site: biomass burning, motor vehicles, marine aerosol and
      crustal matter. Biomass burning was the most dominant source at both sites and
      was responsible for both the evening and morning PM(10) concentration peaks. The
      use of elemental speciation combined with PM(10) concentrations for source
      apportionment on an hourly time-scale has never been reported and provides unique
      and useful information on PM sources for air quality management.

PMID- 22468799
TI  - Is there a low-back cost to hip-centric exercise? Quantifying the lumbar spine
      joint compression and shear forces during movements used to overload the hips.
AB  - The aim of this study was to quantify joint compression and shear forces at L4/L5
      during exercises used to overload the hips. Nine men performed 36 "walking"
      trials using two modalities: (1) sled towing and (2) exercise bands placed around
      the ankles. Participants completed forward, backward, and lateral trials with
      bent and straight legs at three separate loads. Surface electromyography (EMG)
      was recorded bilaterally from eight torso and thigh sites, upper body and lumbar
      spine motion were quantified, and hand forces were measured. An EMG-driven
      musculoskeletal model was used to estimate the muscular contribution to joint
      compression and shear. Peak reaction, muscle and joint compression and shear
      forces, and peak gluteus medius and maximus activity were calculated. Significant
      differences were noted in each dependent measure; however, they were dependent on
      direction of travel, leg position, and load. The highest joint compression and
      shear forces for the sled and band conditions were 4378 N and 626 N, and 3306 N
      and 713 N, respectively. In general, increasing the band tension had little
      effect on all dependent measures, although a load-response was found during the
      sled conditions. Before using any exercise to improve hip function, the potential
      benefits should be weighed against "costs" to neighbouring joints.

PMID- 22468800
TI  - Inflammation-related gene expression profiles of endocervical polyps.
AB  - The roles of inflammation-associated genes in the pathogenesis of endocervical
      polyps remain unclear. We thus compared the expression levels of 509 inflammation
      associated genes between endocervical polyp tissues and endocervical canal
      membrane tissues using a gene microarray. Sixteen inflammation-related genes were
      differentially expressed in endocervical polyps compared with those of normal
      endocervical canal membrane tissues. Expression of 8 of these 16 genes was
      further validated biochemically. The protein expression levels of IL-12P40, IL
      17, IFN-gamma, TNF-alpha, CCR2, and IL-11 were significantly higher in
      endocervical polyps than those in endocervical canal tissues, while expression of
      TGF-beta1 and IL-10 was significantly lower (P<0.05). In addition, endocervical
      polyp tissues expressed IL-12P40, IL-17, IFN-gamma, TNF-alpha, CCR2, IL-11, TGF
      beta1, and IL-10 mainly in the cytoplasm of the inflammatory cells and, to a
      lesser extent, in the acinus of the serous gland. Endocervical polyp is a
      polygenic disease and aberrantly expressed genes may play roles in its
      pathogenesis.

PMID- 22468801
TI  - Metacognition influences item-method directed forgetting.
AB  - In 4 experiments, we examined whether metacognitive beliefs about item
      memorability influence item-method directed forgetting. In Experiment 1,
      participants studied loud and quiet items, which were subsequently cued as to-be
      remembered (TBR) or to-be-forgotten (TBF). Typically, the volume of stimuli does
      not influence recall, although loud items are judged as more memorable than quiet
      items (Rhodes & Castel, 2009). In contrast, we found a recall advantage for loud
      items in directed forgetting, although this was observed for TBR items but not
      TBF items. The loud item advantage disappeared in Experiment 2, when we
      eliminated all TBF trials and instead inserted additional trials during which
      participants could engage in extra rehearsal of earlier presented items. In
      Experiments 3 and 4, a recall advantage for loud items was observed again when
      items were assigned a mixture of positive and negative values, but it did not
      emerge when items were assigned graded positive values. Overall, the results
      showed that the recall advantage for loud items emerges only in response to the
      need to forget some items. We propose 2 mechanisms to account for these results
      either participants select to rehearse loud items as a controlled strategy that
      allows them to forget some items, or they have an unconscious preference for loud
      items that emerges only in response to the need to forget.

PMID- 22468802
TI  - Inhibitory control in memory: evidence for negative priming in free recall.
AB  - Cognitive control mechanisms--such as inhibition--decrease the likelihood that
      goal-directed activity is ceded to irrelevant events. Here, we use the action of
      auditory distraction to show how retrieval from episodic long-term memory is
      affected by competitor inhibition. Typically, a sequence of to-be-ignored spoken
      distracters drawn from the same semantic category as a list of visually presented
      to-be-recalled items impairs free recall performance. In line with competitor
      inhibition theory (Anderson, 2003), free recall was worse for items on a probe
      trial if they were a repeat of distracter items presented during the previous,
      prime, trial (Experiment 1). This effect was produced only when the distracters
      were dominant members of the same category as the to-be-recalled items on the
      prime. For prime trials in which distracters were low-dominant members of the to
      be-remembered item category or were unrelated to that category--and hence not
      strong competitors for retrieval--positive priming was found (Experiments 2 and
      3). These results are discussed in terms of inhibitory approaches to negative
      priming and memory retrieval.

PMID- 22468803
TI  - Phonological overlap affects lexical selection during sentence production.
AB  - Theories of lexical production differ in whether they allow phonological
      processes to affect lexical selection directly. Whereas some accounts, such as
      interactive activation accounts, predict (weak) early effects of phonological
      processes during lexical selection via feedback connections, strictly serial
      architectures do not make this prediction. We present evidence from lexical
      selection during unscripted sentence production that lexical selection is
      affected by the phonological form of recently produced words. In a video
      description experiment, participants described scenes that were compatible with
      several near-meaning-equivalent verbs. We found that speakers were less likely
      than expected by chance to select a verb form that would result in phonological
      onset overlap with the subject of the sentence. Additional evidence from the
      distribution of disfluencies immediately preceding the verb argues that this
      effect is due to early effects on lexical selection, rather than later corrective
      processes, such as self-monitoring. Taken together, these findings support
      accounts that allow early feedback from phonological processes to word-level
      nodes, even during lexical selection.

PMID- 22468804
TI  - The role of sound symbolism in language learning.
AB  - Certain correspondences between the sound and meaning of words can be observed in
      subsets of the vocabulary. These sound-symbolic relationships have been suggested
      to result in easier language acquisition, but previous studies have explicitly
      tested effects of sound symbolism on learning category distinctions but not on
      word learning. In 2 word learning experiments, we varied the extent to which
      phonological properties related to a rounded-angular shape distinction and we
      distinguished learning of categories from learning of individual words. We found
      that sound symbolism resulted in an advantage for learning categories of sound
      shape mappings but did not assist in learning individual word meanings. These
      results are consistent with the limited presence of sound symbolism in natural
      language. The results also provide a reinterpretation of the role of sound
      symbolism in language learning and language origins and a greater specification
      of the conditions under which sound symbolism proves advantageous for learning.

PMID- 22468805
TI  - Everyday attention failures: an individual differences investigation.
AB  - The present study examined individual differences in everyday attention failures.
      Undergraduate students completed various cognitive ability measures in the
      laboratory and recorded everyday attention failures in a diary over the course of
      a week. The majority of attention failures were failures of distraction or mind
      wandering in educational contexts (in class or while studying). Latent variable
      techniques were used to perform analyses, and the results suggested that
      individual differences in working memory capacity and attention control were
      related to some but not all everyday attention failures. Furthermore, everyday
      attention failures predicted SAT scores and partially accounted for the relation
      between cognitive abilities and SAT scores. These results provide important
      evidence for individual differences in everyday attention failures as well as for
      the ecological validity of laboratory measures of working memory capacity and
      attention control.

PMID- 22468806
TI  - A phase II multicenter study of two different dosages of pemetrexed given in
      combination with cyclophosphamide as first-line treatment in patients with
      locally advanced or metastatic breast cancer.
AB  - Pemetrexed/cyclophosphamide was evaluated as first-line treatment for patients
      with locally advanced/metastatic breast cancer. In this randomized phase II study
      (NCT00190671), therapy consisted of either 600 mg/m(2) (P600) or 1,800 mg/m(2)
      (P1800) pemetrexed, followed by 600 mg/m(2) cyclophosphamide, every 21 days; 103
      females (42 P600; 61 P1800) were enrolled. P600 was discontinued, as response
      rate (19.1%) was lower than targeted. In the P1800 arm, 20 patients had partial
      response (32.8%; 95% CI: 21.0-44.6) and 26 (42.6%) had stable disease. Median
      progression-free survival was 6.3 months (range: 0.3-31.1). P1800 plus
      cyclophosphamide 600 represents a regimen of reasonable efficacy and acceptable
      tolerability.

PMID- 22468807
TI  - Dynamic negative compressibility of few-layer graphene, h-BN, and MoS2.
AB  - We report a novel mechanical response of few-layer graphene, h-BN, and MoS(2) to
      the simultaneous compression and shear by an atomic force microscope (AFM) tip.
      The response is characterized by the vertical expansion of these two-dimensional
      (2D) layered materials upon compression. Such effect is proportional to the
      applied load, leading to vertical strain values (opposite to the applied force)
      of up to 150%. The effect is null in the absence of shear, increases with tip
      velocity, and is anisotropic. It also has similar magnitudes in these solid
      lubricant materials (few-layer graphene, h-BN, and MoS(2)), but it is absent in
      single-layer graphene and in few-layer mica and Bi(2)Se(3). We propose a physical
      mechanism for the effect where the combined compressive and shear stresses from
      the tip induce dynamical wrinkling on the upper material layers, leading to the
      observed flake thickening. The new effect (and, therefore, the proposed
      wrinkling) is reversible in the three materials where it is observed.

PMID- 22468808
TI  - Exome sequencing: a transient technology for molecular diagnostics?

PMID- 22468809
TI  - Spatiotemporal individual genome code-lifestyle network: revolutionizing personal
      diagnostics.

PMID- 22468810
TI  - In vivo microbial antigen discovery: finding the 'needle in the haystack'.

PMID- 22468811
TI  - Discrepancies in testing recommendations for Clostridium difficile infection:
      updated review favors amplification test systems.

PMID- 22468813
TI  - Screening for latent infection with Mycobacterium tuberculosis: a plea for
      targeted testing in low endemic regions.
AB  - The higher specificity proposed for IFN-gamma-release assays (IGRAs) compared
      with tuberculin skin testing (TST) may indicate superiority in identifying
      patients at risk for progression towards active tuberculosis. Unfortunately,
      available assays may frequently show discordant results. To aid in interpreting
      discordant results, the article under evaluation has comparatively analyzed
      results of the TST and two commercially available IGRAs in a low-risk population
      for tuberculosis. TST-positive/IGRA-negative results were strongly associated
      with bacillus Calmette-Guerin vaccination or nontuberculous mycobacteria
      sensitization, whereas the etiology of TST-negative/IGRA-positive results or
      discrepancies among IGRAs remain unresolved. As the three tests identified
      different individuals in the majority of positive cases, this indicates that most
      positive results obtained in the absence of additional risk factors are falsely
      positive. By contrast, increasing concordance of positive results was associated
      with tuberculosis risk factors. This has direct implications for screening
      practices in low prevalence regions where a targeted screening approach may
      reduce both unnecessary testing and treatment.

PMID- 22468814
TI  - Mass spectrometry-based protein assays for in vitro diagnostic testing.
AB  - Mass spectrometry-based protein assays hold great promise for in vitro diagnostic
      testing. Technological advances in mass spectrometry have given rise to
      instruments and methods that are fully capable of automated and high-throughput
      protein assaying. Yet, the numerous steps involved in such assays can lead to
      difficulties in assay characterization and validation, and can also make them
      unnecessarily complex and prohibitively expensive for everyday use.
      Simplification of both approaches and instrumentation seems to be the solution to
      the fast introduction of the mass spectrometry-based assays into the clinical
      laboratories. One such simplified approach is the mass spectrometric immunoassay,
      which couples targeted immunoaffinity protein separation with the power of mass
      spectrometry detection. Several mass spectrometric immunoassays have been
      extensively characterized and have found their way into clinical laboratory
      improvement amendments-certified laboratories in the form of laboratory developed
      tests. Reviewed in this special report is the development and validation of one
      of those assays - a Cystatin mass spectrometric immunoassay. With the added
      advantage of protein variant detection and quantification, these assays can
      redefine our view of protein diversity, with clear implications in biomarker
      discovery, validation, and ultimately, in vitro diagnostic testing.

PMID- 22468815
TI  - Exome versus transcriptome sequencing in identifying coding region variants.
AB  - The advent of next-generation sequencing technologies has revolutionized the
      study of genetic variation in the human genome. Whole-genome sequencing currently
      represents the most comprehensive strategy for variant detection genome-wide but
      is costly for large sample sizes, and variants detected in noncoding regions
      remain largely uninterpretable. By contrast, whole-exome sequencing has been
      widely applied in the identification of germline mutations underlying Mendelian
      disorders, somatic mutations in various cancers and de novo mutations in
      neurodevelopmental disorders. Since whole-exome sequencing focuses upon the
      entire set of exons in the genome (the exome), it requires additional exome
      enrichment steps compared with whole-genome sequencing. Although the availability
      of multiple commercial exome-enrichment kits has made whole-exome sequencing
      technically feasible, it has also added to the overall cost. This has led to the
      emergence of transcriptome (or RNA) sequencing as a potential alternative
      approach to variant detection within protein coding regions, since the
      transcriptome of a given tissue represents a quasi-complete set of transcribed
      genes (mRNAs) and other noncoding RNAs. A further advantage of this approach is
      that it bypasses the need for exome enrichment. Here we discuss the relative
      merits and limitations of these approaches as they are applied in the context of
      variant detection within gene coding regions.

PMID- 22468816
TI  - Detection of copy number alterations in acute myeloid leukemia and
      myelodysplastic syndromes.
AB  - Chromosomal deletions and amplifications that occur in affected cells from
      patients with myelodysplastic syndromes and acute myeloid leukemia often contain
      genes that contribute to disease pathogenesis. Identification of copy number
      alterations (deletions and amplifications) and regions of copy neutral loss of
      heterozygosity using array-based platforms has led to the identification of genes
      that are commonly mutated in myeloid malignancies. In this article, we review the
      literature and highlight the array-based studies that directly compare matched
      normal and tumor samples from the same individual to identify somatic
      alterations. We also discuss the use of next-generation sequencing to identify
      all types of structural variants, including copy number alterations and copy
      neutral loss of heterozygosity, and provide an outlook for how this technology
      may be used to interrogate cancer genomes.

PMID- 22468817
TI  - Insights revealed by high-throughput genomic arrays in nonglial primary brain
      tumors.
AB  - Primary CNS tumors (PCNSTs) encompass a broad and heterogeneous group of tumors,
      including gliomas, meningiomas, embryonal tumors, primary CNS lymphomas, CNS germ
      cell tumors and sellar region tumors. In recent decades, research has focused on
      understanding the clinical and biological significance of molecular abnormalities
      detected in PCNSTs. The emergence of genomic arrays, including comparative
      genomic hybridization and SNP arrays, have helped in the discovery of novel
      critically important genes and novel genomic biomarkers involved in PCNST
      oncogenesis (e.g., BRAF duplication in pilocytic astrocytoma). Since a summary of
      data from genomic arrays using gliomas has been described in a previous review,
      in this article we will focus on the insights provided by genome-wide DNA arrays
      in the genetics and genomics of nonglial PCNSTs in adults. The high-throughput
      assessment of gene copy-number abnormalities has improved our knowledge of
      molecular pathogenesis in nonglial PCNSTs, allowing for the identification of new
      candidate genomic regions and genes involved in tumorigenesis. These chromosome
      imbalances provide a promising insight into potential targets for innovative
      drugs and new interesting diagnostic and prognostic biomarkers for clinical
      practice.

PMID- 22468818
TI  - Epigenetic and genetic alterations-based molecular classification of head and
      neck cancer.
AB  - The long-term survival rates for patients diagnosed with advanced head and neck
      cancer (HNC) remain poor. Many perplexing factors, including etiology and
      comorbidity, lead to different molecular malfunctions of HNC cells and determine
      the prognosis of the disease. Traditional diagnostic methods are limited in that
      they fail to provide an effective classification diagnosis, such as a more
      precise prediction of prognosis and decisions for personalized treatment
      regimens. Recently, molecular biology techniques, especially epigenetic and
      genetic techniques, have been developed that have enabled us to gain a greater
      insight into the molecular pathways underlying the cancers. Translating the
      research into a format that will facilitate effective molecular classification,
      support personalized treatment and determine prognosis remains a challenge. In
      this review, the authors provide an overview of cancer epigenetic and genetic
      alterations, tissue banks, and several promising biomarkers or candidates that
      may ultimately prove to be beneficial in a clinical setting for patients with
      HNC.

PMID- 22468819
TI  - Functional drug-gene interactions in lung cancer.
AB  - Despite the dawn of the genomic information era, the challenges of cancer
      treatment remain formidable. Particularly for the most prevalent cancer types,
      including lung cancer, successful treatment of metastatic disease is rare and
      escalating costs for modern targeted drugs place an increasing strain on
      healthcare systems. Although powerful diagnostic tools to characterize individual
      tumor samples in great molecular detail are becoming rapidly available, the
      transformation of this information into therapy provides a major challenge. A
      fundamental difficulty is the molecular complexity of cancer cells that often
      causes drug resistance, but can also render tumors exquisitely sensitive to
      targeted agents. By using lung cancer as an example, we outline the principles
      that govern drug sensitivity and resistance from a genetic perspective and
      discuss how in vitro chemical-genetic screens can impact on patient
      stratification in the clinic.

PMID- 22468821
TI  - Where are my hands? Influence of limb posture on tactile extinction.
AB  - OBJECTIVE: Tactile localization on the skin involves both a somatotopic and a
      postural schema (body-schema) representation. The present study determines the
      extent to which body posture influences tactile perception in right-brain-damaged
      patients. METHOD: In a first set of experiments, patients were asked to detect
      single tactile stimulation delivered to their left or right hands or to both
      hands simultaneously (double stimulation) in different arm postures. Only
      patients who had no difficulty localizing single and double tactile stimulations
      when their hands were placed in anatomic position were tested. Participant's
      hands were crossed, one over the other, and the tactile stimuli were delivered
      either to the hand (beyond the crossing point, Experiment 1) or to the forearm
      (before the crossing point, Experiment 2). In Experiment 3, the left hand was
      placed in the right hemispace and the right hand in the left hemispace without
      crossing over (opposite condition). In a second set of experiments, patients were
      asked to detect stimulation delivered to the forefinger. The fingers were
      crossed, one over the other at the level of the middle phalanx, and stimuli were
      delivered either beyond or before the crossing point. RESULTS: In all
      experimental conditions, control participants performed at ceiling. We observed a
      left-hand tactile extinction on double stimulation in the crossed condition.
      CONCLUSIONS: These results suggest that tactile stimuli can be encoded based on
      multiple specific body-part representations rather than on an integrated body
      schema representation.

PMID- 22468820
TI  - Progress in circulating tumor cell capture and analysis: implications for cancer
      management.
AB  - The hematogenous dissemination of cancer and development of distant metastases is
      the cause of nearly all cancer deaths. Detection of circulating tumor cells
      (CTCs) as a surrogate biomarker of metastases has gained increasing interest.
      There is accumulating evidence on development of novel technologies for CTC
      detection, their prognostic relevance and their use in therapeutic response
      monitoring. Many clinical trials in the early and metastatic cancer setting,
      particularly in breast cancer, are including CTCs in their translational research
      programs and as secondary end points. We summarize the progress of detection
      methods in the context of their clinical importance and speculate on the
      possibilities of wider implementation of CTCs as a diagnostic oncology tool, the
      likelihood that CTCs will be used as a useful biomarker, especially to monitor
      therapeutic response, and what may be expected from the future improvements in
      technologies.

PMID- 22468822
TI  - Executive functions in girls with ADHD followed prospectively into young
      adulthood.
AB  - OBJECTIVE: We prospectively followed an ethnically and socioeconomically diverse
      sample of girls with ADHD (n = 140) and a matched comparison group (n = 88) into
      young adulthood (Mage = 19.6), 10 years after childhood initial assessments, to
      evaluate neuropsychological functioning. We hypothesized that neuropsychological
      deficits would persist through young adulthood for those with ADHD, and that
      those with continuing ADHD symptomatology in young adulthood would show the
      largest impairments. METHOD: Neuropsychological measures at follow-up emphasized
      executive functions (EF) including planning, organization, inhibitory control,
      sustained attention, working memory, and set shifting. RESULTS: Parallel to
      findings from childhood and adolescence, the girls with childhood-diagnosed ADHD
      displayed medium to large deficits in EF relative to comparisons at follow-up,
      even with statistical control of baseline demographic and comorbidity variables.
      The addition of IQ as a covariate attenuated differences but several remained
      significant. Comparisons between the inattentive and combined subtypes of ADHD
      yielded nonsignificant results with small effect sizes. EF impairments were
      evident in both participants whose ADHD diagnoses persisted and in those whose
      ADHD symptoms had remitted to a nondiagnosable level; both subgroups had more EF
      deficits than those who did not meet criteria for ADHD in either childhood or
      young adulthood. CONCLUSIONS: Those in both the persistent and remitted ADHD
      groups showed impairments in EF relative to comparisons and generally did not
      differ from each other. Overall, childhood ADHD in girls portends
      neuropsychological/EF deficits that persist for at least 10 years.

PMID- 22468823
TI  - Predictors of postconcussive symptoms 3 months after mild traumatic brain injury.
AB  - OBJECTIVE: There is continuing controversy regarding predictors of poor outcome
      following mild traumatic brain injury (mTBI). This study aimed to prospectively
      examine the influence of preinjury factors, injury-related factors, and
      postinjury factors on outcome following mTBI. METHOD: Participants were 123
      patients with mTBI and 100 trauma patient controls recruited and assessed in the
      emergency department and followed up 1 week and 3 months postinjury. Outcome was
      measured in terms of reported postconcussional symptoms. Measures included the
      ImPACT Post-Concussional Symptom Scale and cognitive concussion battery,
      including Attention, Verbal and Visual memory, Processing Speed and Reaction Time
      modules, pre- and postinjury SF-36 and MINI Psychiatric status ratings, VAS Pain
      Inventory, Hospital Anxiety and Depression Scale, PTSD Checklist-Specific, and
      Revised Social Readjustment Scale. RESULTS: Presence of mTBI predicted
      postconcussional symptoms 1 week postinjury, along with being female and
      premorbid psychiatric history, with elevated HADS anxiety a concurrent indicator.
      However, at 3 months, preinjury physical or psychiatric problems but not mTBI
      most strongly predicted continuing symptoms, with concurrent indicators including
      HADS anxiety, PTSD symptoms, other life stressors and pain. HADS anxiety and age
      predicted 3-month PCS in the mTBI group, whereas PTSD symptoms and other life
      stressors were most significant for the controls. Cognitive measures were not
      predictive of PCS at 1 week or 3 months. CONCLUSIONS: Given the evident influence
      of both premorbid and concurrent psychiatric problems, especially anxiety, on
      postinjury symptoms, managing the anxiety response in vulnerable individuals with
      mTBI may be important to minimize ongoing sequelae.

PMID- 22468824
TI  - End-of-life care for gay, lesbian, bisexual and transgender people.
AB  - There is little understanding in Australia of the special issues faced by gay,
      lesbian, bisexual and transgender people in end-of-life care and advance care
      planning. This exploratory study aimed to achieve an initial understanding of
      these issues to inform the development of a larger study involving gay, lesbian,
      bisexual and transgender service users. Consultations were carried out with 19
      service providers and 6 gay, lesbian, bisexual and transgender community members
      in the Northern Rivers and metropolitan Sydney areas of New South Wales,
      Australia. Participants reported barriers to health care service access due to
      discrimination, inappropriate care and lack of knowledge among both consumers and
      health care workers of legal rights at the end of life. While advance care
      planning can assist with improving end-of-life care, respondents reported a
      number of obstacles. These included a lack of knowledge and absence of perceived
      need and the additional obstacle of social isolation, leading to difficulties
      identifying alternative decision-makers. The study highlighted the need for
      education for gay, lesbian, bisexual and transgender people and health and aged
      care providers on existing legal provisions to prevent discrimination in end-of
      life care.

PMID- 22468825
TI  - Simultaneous determination of synephrine, arecoline, and norisoboldine in Chinese
      patent medicine Si-Mo-Tang oral liquid preparation by strong cation exchange high
      performance liquid chromatography.
AB  - CONTEXT: Chinese patent medicine Si-Mo-Tang oral liquid preparation (SMT) is
      composed of Aucklandia luppa Decne (Compositae), Citrus aurantium Linn
      (Rutaceae), Lindera aggregata (Sims) Kosterm (Lauraceae), and Areca catechu Linn
      (Arecaceae). Studies of SMT have been impeded due to the lack of quality control
      methods. OBJECTIVE: This study aimed to simultaneously determine three alkaloids
      including synephrine, arecoline, and norisoboldine in SMT for the first time.
      MATERIALS AND METHODS: A strong cation exchange (SCX) high performance liquid
      chromatography (HPLC) method was developed to simultaneously determine
      synephrine, arecoline, and norisoboldine in SMT, and was compared with ion
      pairing chromatography using regular reversed-phase chromatography columns.
      System suitability parameters of synephrine, arecoline, and norisoboldine using
      the SCX chromatography column were investigated. RESULTS: Results demonstrated
      that good separations were achieved on an Agilent SCX (250 * 4.6 mm, 5 um) column
      at 35  degrees C. The mobile phase consisting of methanol-0.2% phosphoric acid
      was delivered at a constant flow of 1.0 mL min(-1) and the eluent was monitored
      at 215 nm. The HPLC method showed good linearity for the examined concentration
      ranges of 2.55-255.0, 1.30-208.0, and 2.06-201.6 ug mL(-1) for synephrine,
      arecoline, and norisoboldine, respectively. The limits of quantification (S/N =
      10) were 2.55, 1.30, and 2.06 ug mL(-1), the limits of detection (S/N = 3) were
      1.53, 0.78, and 1.21 ug mL(-1), and average recoveries were 98.99, 95.63 and
      99.04%, respectively, for synephrine, arecoline, and norisoboldine. DISCUSSION
      AND CONCLUSION: This method has been successfully applied to determine
      synephrine, arecoline, and norisoboldine in Chinese patent medicine SMT.

PMID- 22468826
TI  - Coulombic aggregations of Mn(III) salen-type complexes and Keggin-type
      polyoxometalates: isolation of Mn2 single-molecule magnets.
AB  - The reaction of Mn(III) salen-type complexes with di- and tetraanionic alpha
      Keggin-type polyoxometalates (POMs) was performed, and three types of Coulombic
      aggregations containing Mn(III) out-of-plane dimeric units (abbreviated as
      [Mn(2)](2+)) that are potentially single-molecule magnets (SMMs) with an S(T) = 4
      ground state were synthesized: [Mn(2)(5-MeOsaltmen)(2)(acetone)(2)][SW(12)O(40)]
      (1), [Mn(2)(salen)(2)(H(2)O)(2)](2)[SiW(12)O(40)] (2), and [Mn(5
      Brsaltmen)(H(2)O)(acetone)](2)[{Mn(2)(5-Brsaltmen)(2)}(SiW(12)O(40))] (3), where
      5-Rsaltmen(2-) = N,N'-(1,1,2,2-tetramethylethylene)bis(5-R-salicylideneiminate)
      with R = MeO (methoxy), Br (bromo) and salen(2-) = N,N'
      ethylenebis(salicylideneiminate). Compound 1 with a dianionic POM,
      [SW(12)O(40)](2-), is composed of a 1:1 aggregating set of [Mn(2)](2+)/POM, and
      2, with a tetraanionic POM, [SiW(12)O(40)](4-), is a 2:1 set. Compound 3 with
      [SiW(12)O(40)](4-) forms a unique 1D coordinating chain with a [-{Mn(2)}-POM-](2
      ) repeating unit, for which a hydrogen-bonded dimeric unit ([Mn(5
      Brsaltmen)(H(2)O)(acetone)](2)(2+)) is present as a countercation. Independent of
      the formula ratio of [Mn(2)](2+)/POM, Mn(III) dimers and POM units in 1-3 form
      respective segregated columns along a direction of the unit cell, which make an
      alternate packing to separate evenly identical species in a crystal. The nearest
      intermolecular Mn...Mn distance is found in the order 2 < 3 < 1. The segregation
      of the [Mn(2)](2+) dimer resulted in interdimer distances long enough to
      effectively reduce the intermolecular magnetic interaction, in particular in 1
      and 3. Consequently, an intrinsic property, SMM behavior, of Mn(III) dimers has
      been characterized in this system, even though the interdimer interactions are
      still crucial in the case of 2, where a long-range magnetic order competitively
      affects slow relaxation of the magnetization at low ac frequencies.

PMID- 22468827
TI  - Active control of silver nanoparticles spacing using dielectrophoresis for
      surface-enhanced Raman scattering.
AB  - We demonstrate an active microfluidic platform that integrates dielectrophoresis
      for the control of silver nanoparticles spacing, as they flow in a liquid
      channel. By careful control of the nanoparticles spacing, we can effectively
      increase the surface-enhanced Raman scattering (SERS) signal intensity based on
      augmenting the number of SERS-active hot-spots, while avoiding irreversible
      aggregation of the particles. The system is benchmarked using dipicolinate (2,6
      pyridinedicarboxylic acid) (DPA), which is a biomarker of Bacillus anthracis. The
      validity of the results is discussed using several complementing characterization
      scenarios.

PMID- 22468828
TI  - Interfacial thermal conductance observed to be higher in semiconducting than
      metallic carbon nanotubes.
AB  - Thermal transport at carbon nanotube (CNT) interfaces was investigated by
      characterizing the interfacial thermal conductance between metallic or
      semiconducting CNTs and three different surfactants. We thereby resolved a
      difference between metallic and semiconducting CNTs. CNT portions separated by
      their electronic type were prepared in aqueous suspensions. After slightly
      heating the CNTs dispersed in the suspension, we obtained cooling curves by
      monitoring the transient changes in absorption, and from these cooling curves, we
      extracted the interfacial thermal conductance by modeling the thermal system. We
      found that the semiconducting CNTs unexpectedly exhibited a higher conductance of
      11.5 MW/m(2).K than that of metallic CNTs (9 MW/m(2).K). Meanwhile, the type of
      surfactants hardly influenced the heat transport at the interface. The surfactant
      dependence is understood in terms of the coupling between the low-frequency
      vibrational modes of the CNTs and the surfactants. Explanations for the
      electronic-type dependency are considered based on the defect density in CNTs and
      the packing density of surfactants.

PMID- 22468829
TI  - Termite soldier differentiation in incipient colonies is related to parental
      proctodeal trophallactic behavior.
AB  - Termite soldiers represent a peculiar caste among social insects in terms of
      their specific defensive roles. Numbers of soldiers are relatively low in a
      mature colony, and it is impossible to identify the individuals that will
      differentiate into soldiers. If it were possible to specify these individuals
      prior to soldier differentiation, it would facilitate a better understanding of
      the regulatory mechanisms of soldier differentiation under natural condition.
      Here we analyzed soldier differentiation in incipient colonies of Zootermopsis
      nevadensis, in which only a single soldier develops via a presoldier stage, and
      is stable during early colony ontogeny. We observed that the oldest third instar
      differentiated into a presoldier within about eight days from its appearance.
      Caste differentiation, however, was not strictly determined on an individual
      basis. The oldest third instars never differentiated into presoldiers if primary
      reproductives were removed soon after their appearance. Behavioral observations
      of primary reproductives and their offspring prior to presoldier differentiation,
      showed that primary reproductives transferred proctodeal materials to the oldest
      third instar significantly more frequently than to other larva. A high juvenile
      hormone (JH) titer is required for the soldier differentiation, and we suggest
      that the JH itself or some nutrients/factors increasing larval JH titer may be
      transferred to the oldest third instar via a parental proctodeal fluid.

PMID- 22468830
TI  - Evaluation of mosquito (Diptera: Culicidae) species richness using two sampling
      methods in the hydroelectric reservoir of Simplicio, Minas Gerais, Brazil.
AB  - We compared two types of light traps used for monitoring mosquito abundance in
      the hydroelectric reservoir of Simplicio, Alem Paraiba - Minas Gerais. Mosquitoes
      were captured bimonthly using automatic CDC and Shannon traps before the filling
      of the hydroelectric plant reservoir from December 2008 to December 2009. In
      total, 1474 specimens from 13 genera were captured. Among the captured specimens,
      several species known to be vectors of disease-causing agents for humans and/or
      animals were identified, including Anopheles aquasalis, Aedes albopictus,
      Coquillettidia venezuelensis, Haemagogus leucocelaenus, and Aedes scapularis.
      Sampling efficacy between the four capture sites was not found to be
      significantly different, irrespective of species captured or type of trap used.
      Poor correlation (r (x, y) = -0.0444) between the number of mosquito species and
      capture site was observed when not influenced by the type of trap used. Among the
      installation sites of the CDC and Shannon traps in the areas investigated, CDC
      traps fixed in livestock shelters obtained an overall higher abundance of species
      captured.

PMID- 22468831
TI  - Mitochondrial genome of a Japanese placozoan.
AB  - Placozoans are marine invertebrates found in tropical and subtropical waters.
      Their body plan is among the simplest of free-living animals. The present study
      determined the mitochondrial genome sequence of a placozoan collected on the
      coast of Shirahama, Wakayama, Honshu, Japan, and compared it with those of
      Trichoplax adhaerens from the Red Sea and of three strains from the Caribbean
      Sea. The sequences of mitochondrial respiratory chain of the Japanese placozoan
      genes are very similar to those of the BZ49 strain from the Caribbean Sea.
      However, there are distinct differences in gene arrangement, such as the location
      of two open reading frames. This Japanese placozoan is therefore distinguishable
      from the other strains. Based on current knowledge of placozoan 16S diversity our
      'Shirahama' strain most likely represents the H15 lineage, known from the
      Philippines. In the mitochondrial genome of placozoans, substitution rates are
      slower than in bilaterians, whereas the rate of rearrangements is faster.

PMID- 22468832
TI  - Genetic structure and cryptic diversity of Onychodactylus japonicus (Amphibia,
      Caudata, Hynobiidae) in northeastern Honshu, Japan, as revealed by allozymic
      analysis.
AB  - We conducted a comprehensive allozymic analysis of 393 specimens of the Japanese
      clawed salamander, Onychodactylus japonicus, from 33 populations of northeastern
      Honshu, Japan. As a result, these populations exhibited extensive geographic
      genetic differentiation, and four major genetic groups (N-Tohoku, S-Tohoku,
      Tsukuba, and SW-Honshu groups) were consistently recognized. Of these, the
      Tsukuba group was geographically isolated from all the others, whereas the N- and
      S-Tohoku groups, and the S-Tohoku and SW-Honshu groups, respectively, were nearly
      parapatric, without distinct geographic barriers. The magnitude of genetic
      distances between the four groups, except for between the N- and S-Tohoku groups,
      was as large as that normally found among different hynobiid species. A structure
      analysis detected no admixture of the N- and S-Tohoku groups, whereas few hybrids
      were found between the S-Tohoku and SW-Honshu around their contact zone. However,
      genetic exchange between these parapatric groups appeared to be infrequent,
      suggesting the presence of some isolation mechanisms between them. Within each
      group, only the S-Tohoku group exhibited an extensive level of population genetic
      structure that roughly distinguishes the eastern, central, and northwestern
      subgroups, indicating the complexity of the phylogeographic traits of this group.
      These results strongly suggest that populations of O. japonicus from northeastern
      Japan encompass several cryptic species.

PMID- 22468833
TI  - Population genetic structure and historical demography of the ground beetle
      Pheropsophus jessoensis from the Tsinling-Dabashan Mountains, central China based
      on mitochondrial DNA analysis.
AB  - The population genetic structure and demographic history of the ground beetle
      Pheropsophus jessoensis (Coleoptera: Carabidae) from the Tsinling-Dabashan
      Mountains, central China were estimated using the mtDNACol-tRNALeu-mtDNAColl
      region as a molecular marker. 184 individuals from 25 local populations, were
      collected. The haplotype diversity (H(d)) of total and each individual sampled
      population was high, and was accompanied by lower nucleotide diversity (P(i)).
      AMOVA analysis suggested that most of the variation was within populations
      (92.17%), while differentiation of among populations only contributed 7.83% to
      the total. Mantel test results showed significant correlation between the
      pairwise calculated genetic distance and pairwise calculated geographical
      distance of the populations (R(xy) = 0.360529, P = 0.00001 < 0.01), indicating
      the presence of isolationby-distance. No phylogeographic structure was found
      within the Tsinling-Dabashan Mountains region. Statistical phylogeographic
      analysis indicated that the contemporary populations are derived from multiple
      ancestral-refugial source populations. Gene flow calculated through the N(m) was
      high between many pairs of populations, which was probably due to ancient
      vicariance and subsequent rapid expansion of populations. The results of neutral
      test, mismatch distribution analyses, and Bayesian Skyline Plot (BSP) analysis
      together indicated a sudden demographic expansion. The estimated expansion time
      of individual haplogroup and the whole sampled population were 0.012-0.278 Myr,
      and a sudden expansion was identified between 0.05 Myr to 0.01 Myr by BSP. The
      postglacial population expansion might lead to the lack of phylogeographic
      structure.

PMID- 22468834
TI  - Cypris larvae (Cirripedia: Balanomorpha) display auto-fluorescence in nearly
      species-specific patterns.
AB  - The identification of balanomorph larvae plays an important role in ecological
      study and for protection against biofouling. However, it is difficult to identify
      species of cyprids (settling larvae) of balanomorph barnacles, as they show
      remarkably similar morphology. Some authors have suggested distinguishing cyprids
      of different species by carapace length, pigmentation, and fine carapace detail.
      However, such criteria are only applicable to a narrow range of balanomorph
      species. Recently, we were have serendipitously found species-specific
      distribution of fluorescent substances in cultured cyprids obtained from adult
      balanomorph barnacles, collected near the coast of Japan. Fluorescent patterns
      (FPs) of cyprids from 11 species were classified into five major groups. Cyprids
      specimens collected from the field were estimated, based on the FPs and other
      morphological characteristics (pigmentation and carapace length), after which
      their species were identified using the following two criteria: the morphology of
      adults derived from the field cyprids that adhered to a culture dish, and cyprid
      12S rRNA gene sequence. The results of species estimation by FPs largely
      corresponded to the correct species identification. Other FP groups were found in
      the field cyprids. This study of FPs should be helpful for identification of
      cyprid species.

PMID- 22468835
TI  - 11-ketotestosterone synchronously induces oocyte development and silvering
      related changes in the Japanese eel, Anguilla japonica.
AB  - To evaluate the effects of sex steroids on silvering in the Japanese eel,
      Anguilla japonica, the development of oocytes, eye size, digestive tract, and
      swim bladder were studied in relation to observations of the profiles of plasma
      levels of sex steroids (estradiol 17beta, E2; testosterone, T; 11
      ketotestosterone; 11-KT) during silvering for each sex and by administrating 11
      KT to yellow eels. All steroids examined in the study increased in female eels
      after silvering had begun, whereas in males, only 11-KT increased significantly,
      and no statistical differences were found in plasma levels of E2 and T between
      eels in both developmental stages. 11-KT appeared to induce the early stage of
      oocyte growth, enlargement of the eyes, degeneration of the digestive tract and
      the development of the swim bladder. This suggested that 11-KT synchronously
      accelerates early development of the ovaries and the morphological changes,
      possibly in adaption to oceanic migration, and that 11-KT is one of the most
      important factors in early stages of development in the Japanese eel, as it
      appears to be in other anguillid eels.

PMID- 22468836
TI  - Fluorescent protein candidate genes in the coral Acropora digitifera genome.
AB  - The vivid coloration of corals depends on fluorescent proteins that include cyan
      (CFP), green (GFP) and red (RFP) fluorescent proteins, and a non-fluorescent
      blue/purple chromoprotein. We examined how many genes encoding fluorescent
      proteins are present in the recently sequenced genome of the coral Acropora
      digitifera. Based on molecular phylogenetic analysis, we found one, five, one,
      and three candidate genes for CFP, GFP, RFP, and chromoprotein, respectively. The
      CFP and GFP genes are clustered in a ~80-kb-long genomic region, suggesting that
      they originated from an ancestral gene by tandem duplication. Since CFP and GFP
      possess the same chromophore, the gene clustering may provide the first genomic
      evidence for a common origin of the two proteins. Comparison between the
      fluorescent protein genes of closely related coral species suggests an expansion
      of chromoprotein genes in the A. digitifera genome, and of RFP genes in the A.
      millepora genome. The A. digitifera fluorescent protein genes are expressed
      during embryonic and larval developmental stages and in adults, suggesting that
      the genes play a variety of roles in coral physiology.

PMID- 22468837
TI  - Existence of two sexual races in the planarian species switching between asexual
      and sexual reproduction.
AB  - In certain planarian species that are able to switch between asexual and sexual
      reproduction, determining whether a sexual has the ability to switch to the
      asexual state is problematic, which renders the definition of sexuals
      controversial. We experimentally show the existence of two sexual races, acquired
      and innate, in the planarian Dugesia ryukyuensis. Acquired sexuals used in this
      study were experimentally switched from asexuals. Inbreeding of acquired sexuals
      produced both innate sexuals and asexuals, but inbreeding of innate sexuals
      produced innate sexuals only and no asexuals. Acquired sexuals, but not innate
      sexuals, were forced to become asexuals by ablation and regeneration (asexual
      induction). This suggests that acquired sexuals somehow retain asexual potential,
      while innate sexuals do not. We also found that acquired sexuals have the
      potential to develop hyperplastic and supernumerary ovaries, while innate sexuals
      do not. In this regard, acquired sexuals were more prolific than innate sexuals.
      The differences between acquired and innate sexuals will provide a structure for
      examining the mechanism underlying asexual and sexual reproduction in planarians.

PMID- 22468838
TI  - Reproduction in female copperhead snakes (Agkistrodon contortrix): plasma steroid
      profiles during gestation and post-birth periods.
AB  - We investigated levels of plasma progesterone (P4), 17beta-estradiol (E2),
      testosterone (T), and corticosterone (CORT) during gestation and post-birth
      periods in wild-collected female copperhead snakes (Viperidae; Agkistrodon
      contortrix). We also sought to determine whether CORT levels at (or near) birth
      dramatically increase and were correlated with duration of labor and litter size.
      Specifically, pregnant subjects (N = 14) were collected during early- to mid
      gestation, held in the laboratory, and repeatedly bled to obtain plasma for
      steroid analyses. Progesterone showed significant changes during gestation, with
      the highest levels at the onset of sampling (circa 50 days prior to birth); P4
      progressively declined up to parturition, and basal levels were observed
      thereafter. At the onset of sampling, E2 was at peak levels and fell sharply at
      circa 30 days prior to birth, a trend observed throughout the post-birth sampling
      period. Throughout the entire sampling period, T was undetectable. Although CORT
      showed no significant changes during gestation and several days following
      parturition, there was a highly significant peak at the time of birth. Our
      findings mirror the results of previous studies on pregnancy and steroid hormones
      of other live-bearing snakes, lizards, and mammals. As expected, there was a
      significant relationship between duration of labor and litter size; however,
      although levels of CORT did not achieve significance, there was a positive trend
      with litter size. We suggest that elevation of CORT at birth is involved in the
      mobilization and regulation of energy stores necessary for the physiological
      process of parturition and as a possible mechanism to trigger birth.

PMID- 22468839
TI  - An overview of the development of combined oral contraceptives containing
      estradiol: focus on estradiol valerate/dienogest.
AB  - Natural estrogens such as estradiol (E(2)) or its valerate ester (E(2)V) offer an
      alternative to ethinyl estradiol (EE). E(2)-containing combined oral
      contraceptives (COCs) have demonstrated sufficient ovulation inhibition and
      acceptable contraceptive efficacy. However, earlier formulations were generally
      associated with unacceptable bleeding profiles. Two E(2)V-containing preparations
      have been approved to date for contraceptive use: E(2)V/cyproterone acetate (CPA)
      (Femilar((r)); only approved in Finland and only in women >40 years or women aged
      35-40 years in whom a COC containing EE is not appropriate) and E(2)V/dienogest
      (DNG; Qlaira((r))/Natazia((r))). The objective of the current review is to
      provide an overview of the development of COCs containing natural estrogen,
      highlighting past issues and challenges faced by earlier formulations, as well as
      the current status and future directions. The majority of information to date
      pertains to the development of E(2)V/DNG.

PMID- 22468840
TI  - Epigenetics and microRNAs in preeclampsia.
AB  - Strong evidence suggests a potential link among epigenetics, microRNAs (miRNAs),
      and pregnancy complications. Much research still needs to be carried out to
      determine whether epigenetic factors are predictive in the pathogenesis of
      preeclampsia (PE), a life-threatening disease during pregnancy. Recently, the
      importance of maternal epigenetic features, including DNA methylation, histone
      modifications, epigenetically regulated miRNA, and the effect of imprinted or non
      imprinted genes on trophoblast growth, invasion, as well as fetal development and
      hypertension in pregnancy, has been demonstrated in a series of articles. This
      article discusses the current evidence of this complicated network of miRNA and
      epigenetic factors as potential mechanisms that may underlie the theories of
      disease for PE. Translating these basic epigenetic findings to clinical practice
      could potentially serve as prognostic biomarkers for diagnosis in its early
      stages and could help in the development of prophylactic strategies.

PMID- 22468841
TI  - New precision limit on the strange vector form factors of the proton.
AB  - The parity-violating cross-section asymmetry in the elastic scattering of
      polarized electrons from unpolarized protons has been measured at a four-momentum
      transfer squared Q2 = 0.624  GeV2 and beam energy E(b) = 3.48  GeV to be A(PV) = 
      23.80 +/- 0.78(stat) +/- 0.36(syst) parts per million. This result is consistent
      with zero contribution of strange quarks to the combination of electric and
      magnetic form factors G(E)(s) + 0.517G(M)(s) = 0.003 +/- 0.010(stat) +/-
      0.004(syst) +/- 0.009(ff), where the third error is due to the limits of
      precision on the electromagnetic form factors and radiative corrections. With
      this measurement, the world data on strange contributions to nucleon form factors
      are seen to be consistent with zero and not more than a few percent of the proton
      form factors.

PMID- 22468842
TI  - Solution structural ensembles of substrate-free cytochrome P450(cam).
AB  - Removal of substrate (+)-camphor from the active site of cytochrome P450(cam)
      (CYP101A1) results in nuclear magnetic resonance-detected perturbations in
      multiple regions of the enzyme. The (1)H-(15)N correlation map of substrate-free
      diamagnetic Fe(II) CO-bound CYP101A permits these perturbations to be mapped onto
      the solution structure of the enzyme. Residual dipolar couplings (RDCs) were
      measured for (15)N-(1)H amide pairs in two independent alignment media for the
      substrate-free enzyme and used as restraints in solvated molecular dynamics (MD)
      simulations to generate an ensemble of best-fit structures of the substrate-free
      enzyme in solution. Nuclear magnetic resonance-detected chemical shift
      perturbations reflect changes in the electronic environment of the NH pairs, such
      as hydrogen bonding and ring current shifts, and are observed for residues in the
      active site as well as in hinge regions between secondary structural features.
      RDCs provide information about relative orientations of secondary structures, and
      RDC-restrained MD simulations indicate that portions of a beta-rich region
      adjacent to the active site shift so as to partially occupy the vacancy left by
      removal of the substrate. The accessible volume of the active site is reduced in
      the substrate-free enzyme relative to the substrate-bound structure calculated
      using the same methods. Both symmetric and asymmetric broadening of multiple
      resonances observed upon substrate removal as well as localized increased errors
      in RDC fits suggest that an ensemble of enzyme conformations are present in the
      substrate-free form.

PMID- 22468843
TI  - Ash particulate formation from pulverized coal under oxy-fuel combustion
      conditions.
AB  - Aerosol particulates are generated by coal combustion. The amount and properties
      of aerosol particulates, specifically size distribution and composition, can be
      affected by combustion conditions. Understanding the formation of these particles
      is important for predicting emissions and understanding potential deposition. Oxy
      fuel combustion conditions utilize an oxygen-enriched gas environment with CO(2).
      The high concentration of CO(2) is a result of recycle flue gas which is used to
      maintain temperature. A hypothesis is that high CO(2) concentration reduces the
      vaporization of refractory oxides from combustion. A high-temperature drop-tube
      furnace was used under different oxygen concentrations and CO(2) versus N(2) to
      study the effects of furnace temperature, coal type, and gas phase conditions on
      particulate formation. A scanning mobility particle sizer (SMPS) and aerodynamic
      particle sizer (APS) were utilized for particle size distributions ranging from
      14.3 nm to 20 MUm. In addition, particles were collected on a Berner low pressure
      impactor (BLPI) for elemental analysis using scanning electron microscopy and
      energy dispersive spectroscopy. Three particle size modes were seen: ultrafine
      (below 0.1 MUm), fine (0.1 to 1.0 MUm), and coarse (above 1 MUm). Ultrafine mass
      concentrations were directly related to estimated particle temperature,
      increasing with increasing temperature. For high silicon and calcium coals, Utah
      Skyline and PRB, there was a secondary effect due to CO(2) and the hypothesized
      reaction. Illinois #6, a high sulfur coal, had the highest amount of ultrafine
      mass and most of the sulfur was concentrated in the ultrafine and fine modes.
      Fine and coarse mode mass concentrations did not show a temperature or CO(2)
      relationship. (The table of contents graphic and abstract graphic are adapted
      from ref 27.).

PMID- 22468844
TI  - Is there a correlation between birth weights and first-trimester crown-rump
      length growth velocity?
AB  - OBJECTIVE: To test the hypothesis that small- or large-for-gestational-age (SGA
      or LGA) newborns have anomalous crown-rump length (CRL) growth rates in the first
      trimester. METHODS: Prospective observational study. Women in the first trimester
      presenting to the Early Pregnancy Unit, between November 2006 and December 2010,
      underwent transvaginal scan. Women with viable singleton pregnancies in the first
      trimester who had at least two CRL measurements > 5 mm, recorded at least 2 weeks
      apart, and also had birth weight data available were included in the final
      analysis. Birth weight percentiles were calculated and adjusted for gestational
      age and gender. SGA was equivalent to < 10th centile and LGA was equivalent to >
      90th centile. Correlation analysis was performed between birthweight percentiles
      and first-trimester CRL growth-rate coefficients. In addition, we estimated early
      fetal growth rates (EFGR) by calculating the Delta CRL/Delta time (mm/day) to see
      if these differed according to the birth-weight percentiles. RESULTS: A total of
      107 women had complete data. The mean maternal characteristics were age 27.5 +/-
      6 years, weight 87 +/- 29 kg and height 163 +/- 8 cm. The mean birth weight and
      gestational age at delivery were 3405 g (SD = 597) and 269 days (SD = 13),
      respectively. The proportions of SGA and LGA were 7.5% and 18.7%, respectively.
      There were no significant correlations between birth-weight percentiles and any
      of the CRL growth rates. There were also no significant differences in the mean
      CRL velocities when comparing the SGA and LGA newborns birth weights. EFGR for
      SGA and LGA newborns were 1.34 mm/day (SD = 0.17) and 1.32 mm/day (SD = 0.24),
      respectively (p > 0.05). CONCLUSIONS: Newborns who are found to be SGA or LGA at
      delivery do not appear to have anomalous CRL growth patterns in the first
      trimester. The EFGR also did not correlate with birth-weight percentiles.

PMID- 22468845
TI  - Effects of a combined treatment with GPR30 agonist G-1 and herceptin on growth
      and gene expression of human breast cancer cell lines.
AB  - Expression of G-protein-coupled receptor 30 (GPR30) is present in HER2
      overexpressing breast cancer. In this study, we examined to what extent GPR30
      agonist G-1 would affect the antitumoral action of trastuzumab (Herceptin).
      Combined treatment with both drugs exerted an additive growth-inhibitory effect
      on breast cancer cells which was accompanied by a significant decline of cyclin
      A2 expression both on the protein and the mRNA level. Combined treatment also
      resulted in expression changes of c-fos, cyclin D1, or p21/WAF-1. The results of
      our study encourage further attempts to test the relevance of these in vitro data
      in the clinical setting.

PMID- 22468846
TI  - Synthetically encoded ultrashort-channel nanowire transistors for fast, pointlike
      cellular signal detection.
AB  - Nanostructures, which have sizes comparable to biological functional units
      involved in cellular communication, offer the potential for enhanced sensitivity
      and spatial resolution compared to planar metal and semiconductor structures.
      Silicon nanowire (SiNW) field-effect transistors (FETs) have been used as a
      platform for biomolecular sensors, which maintain excellent signal-to-noise
      ratios while operating on lengths scales that enable efficient extra- and
      intracellular integration with living cells. Although the NWs are tens of
      nanometers in diameter, the active region of the NW FET devices typically spans
      micrometers, limiting both the length and time scales of detection achievable
      with these nanodevices. Here, we report a new synthetic method that combines gold
      nanocluster-catalyzed vapor-liquid-solid (VLS) and vapor-solid-solid (VSS) NW
      growth modes to produce synthetically encoded NW devices with ultrasharp (<5 nm)
      n-type highly doped (n(++)) to lightly doped (n) transitions along the NW growth
      direction, where n(++) regions serve as source/drain (S/D) electrodes and the n
      region functions as an active FET channel. Using this method, we synthesized
      short-channel n(++)/n/n(++) SiNW FET devices with independently controllable
      diameters and channel lengths. SiNW devices with channel lengths of 50, 80, and
      150 nm interfaced with spontaneously beating cardiomyocytes exhibited well
      defined extracellular field potential signals with signal-to-noise values of ca.
      4 independent of device size. Significantly, these "pointlike" devices yield peak
      widths of ~500 MUs, which is comparable to the reported time constant for
      individual sodium ion channels. Multiple FET devices with device separations
      smaller than 2 MUm were also encoded on single SiNWs, thus enabling multiplexed
      recording from single cells and cell networks with device-to-device time
      resolution on the order of a few microseconds. These short-channel SiNW FET
      devices provide a new opportunity to create nanoscale biomolecular sensors that
      operate on the length and time scales previously inaccessible by other techniques
      but necessary to investigate fundamental, subcellular biological processes.

PMID- 22468847
TI  - Facet personality and surface-level diversity as team mental model antecedents:
      implications for implicit coordination.
AB  - Team mental models (TMMs) have received much attention as important drivers of
      effective team processes and performance. Less is known about the factors that
      give rise to these shared cognitive structures. We examined potential antecedents
      of TMMs, with a specific focus on team composition variables, including various
      facets of personality and surface-level diversity. Further, we examined implicit
      coordination as an important outcome of TMMs. Results suggest that team
      composition in terms of the cooperation facet of agreeableness and racial
      diversity were significantly related to team-focused TMM similarity. TMM
      similarity was also positively predictive of implicit coordination, which
      mediated the relationship between TMM similarity and team performance. Post hoc
      analyses revealed a significant interaction between the trust facet of
      agreeableness and racial diversity in predicting TMM similarity. Results are
      discussed in terms of facilitating the emergence of TMMs and corresponding
      implications for team-related human resource practices.

PMID- 22468848
TI  - Solving the measurement invariance anchor item problem in item response theory.
AB  - The efficacy of tests of differential item functioning (measurement invariance)
      has been well established. It is clear that when properly implemented, these
      tests can successfully identify differentially functioning (DF) items when they
      exist. However, an assumption of these analyses is that the metric for different
      groups is linked using anchor items that are invariant. In practice, however, it
      is impossible to be certain which items are DF and which are invariant. This
      problem of anchor items, or referent indicators, has long plagued invariance
      research, and a multitude of suggested approaches have been put forth.
      Unfortunately, the relative efficacy of these approaches has not been tested.
      This study compares 11 variations on 5 qualitatively different approaches from
      recent literature for selecting optimal anchor items. A large-scale simulation
      study indicates that for nearly all conditions, an easily implemented 2-stage
      procedure recently put forth by Lopez Rivas, Stark, and Chernyshenko (2009)
      provided optimal power while maintaining nominal Type I error. With this
      approach, appropriate anchor items can be easily and quickly located, resulting
      in more efficacious invariance tests. Recommendations for invariance testing are
      illustrated using a pedagogical example of employee responses to an
      organizational culture measure.

PMID- 22468849
TI  - Imaging sites of infection using a 99mTc-labeled folate conjugate targeted to
      folate receptor positive macrophages.
AB  - EC20, a folate-targeted (99m)Tc based radioimaging agent with a high folate
      receptor (FR) binding affinity, has been used for both the diagnosis and the
      staging of FR positive malignancies (currently in phase III trials) and also for
      the localization of inflamed lesions characterized by the accumulation of FR+
      macrophages. Because recent evidence has suggested that FR+ macrophages might
      accumulate at sites of infectious disease, this study evaluated whether EC20
      might prove similarly useful for imaging bacterial infection foci. Using gamma
      scintigraphic imaging, it was demonstrated that EC20 accumulated at sites of
      Staphylococcus aureus infection with a significant difference (P < 0.0001, n =
      12) in enrichment noted between infected and noninfected limbs. Confirmation that
      the elevated uptake of EC20 in infected limbs was FR-mediated was supported by
      suppression of EC20 accumulation in the presence of a 200-fold excess of free
      folic acid (P < 0.0001, n = 12). This study establishes for the first time the
      use of EC20 to image and localize sites of infectious disease.

PMID- 22468850
TI  - "When the age is in, the wit is out": age-related self-categorization and deficit
      expectations reduce performance on clinical tests used in dementia assessment.
AB  - This study examined the combined effects of age-based self-categorization and
      aging expectations on cognitive performance in a clinical context. An
      experimental study manipulated older adults' salient self-categorization as
      Younger or Older, as well as expectations that aging involves a specific memory
      decline versus generalized cognitive decline. Memory and general ability tests
      that are typically used in dementia screening were then administered. As
      predicted, self-categorization as Older dramatically reduced performance, but the
      measure on which this effect was revealed depended on aging expectations.
      Participants who self-categorized as Older and expected memory to decline
      performed worse on memory tests. Conversely, participants who self-categorized as
      Older and expected widespread cognitive decline performed worse on the general
      ability test. The clinical implications for the latter group were profound,
      because 70% met the diagnostic criterion for dementia, compared with an average
      of 14% in other conditions. The importance of self-categorization processes when
      interpreting performance on tests used to diagnose dementia are discussed.

PMID- 22468851
TI  - The role of task preparation and task inhibition in age-related task-switching
      deficits.
AB  - The aim of our study was to examine the role of task preparation and task
      inhibition in age-related task-switching deficits. In 2 experiments, we used a
      cuing paradigm with 3 tasks and manipulated the cue-stimulus interval (CSI).
      Additionally, switching among 3 tasks enabled us to examine n-2 task repetition
      costs, which reflect persisting inhibition of abandoned tasks. In Experiment 1,
      we found larger mixing costs (i.e., performance in mixed-task blocks vs. single
      task blocks) in older adults than in young adults, and preparation effects were
      smaller in older adults than in young adults. In Experiment 2, where CSIs were
      blocked instead of randomly varied, we replicated reduced effects of task
      preparation in older adults. N-2 task repetition costs were not significant in
      Experiment 1 but significant in Experiment 2, and these costs did not differ
      across age groups in both experiments. The data suggest a task-preparation
      deficit in older adults that contributes to increased mixing costs in older
      adults.

PMID- 22468853
TI  - 'Lived Islam' in India and Bangladesh: negotiating religion to realise
      reproductive aspirations.
AB  - This paper seeks to answer the question of how Muslim women interpret and
      negotiate religion in order to realise their reproductive aspirations. A close
      reading of lived experiences of 32 Muslim women from a varied educational
      background yields a wider perspective of the different interpretations of
      reproductive norms employed by adherents of the same religion (Islam), situated
      in two countries (India/Bangladesh) and group (majority/minority) contexts.
      Further, this comparative study yields a deeper understanding of agency that is
      employed by Muslim participants in each country. Muslim women - both in India and
      Bangladesh - are not passive followers of religious norms, but have agency to
      bring change in their own life and take an active role in planning their family,
      thereby transgressing religious norms in reproductive matters. Muslim women in
      India exercise their agency by adopting sterilisation - a method proscribed by
      Islam - without the knowledge of their significant others. Muslim women in
      Bangladesh use their agency by making a flexible interpretation of Islam in
      reproductive matters. A lesson learned from this comparative study is the need to
      remove barriers that prevent the adoption of contraceptives by Muslim minorities
      in India and to design family planning programmes that takes into account their
      religious needs.

PMID- 22468852
TI  - Terpenoidal constituents of Eucalyptus loxophleba ssp. lissophloia.
AB  - CONTEXT: Eucalyptus has been a source of a number of biologically active
      compounds. The anti-leishmanial activity of terpenoids from Eucalyptus loxophleba
      (Benth.) ssp. lissophloia (Myrtaceae) has not yet been investigated. OBJECTIVE:
      Isolation of the terpenoidal constituents for evaluation of in vitro anti
      leishmanial activity against the Leishmania donovani (Dd8 strain) promastigotes.
      MATERIALS AND METHODS: The chloroform-methanol (8:2) extract of dried leaves of
      Eucalyptus loxophleba was used to isolate terpenoidal constituents employing
      solvent partitioning, column chromatography and preparative high performance
      liquid chromatography and characterized from spectral data. The anti-leishmanial
      activity of the isolated compounds was tested in vitro using an Alamar blue assay
      against a culture of L. donovani (Dd8 strain) promastigotes. RESULTS: Two new
      naturally occurring triterpenes, named loxanic acid and 3-acetyl loxanic acid
      together with four known ursane triterpenoids and one bis-monoterpene glycoside,
      cuniloside B isolated from the leaves showed anti-leishmanial activity (IC(50)
      133 to 235 MUM) against the promastigotes of the tested strain. CONCLUSION: The
      terpenes isolated from the leaves of E. loxophleba showed moderate anti
      leishmanial activity.

PMID- 22468854
TI  - Advanced DNA assembly technologies in drug discovery.
AB  - Recombinant DNA technologies have had a fundamental impact on drug discovery. The
      continuous emergence of unique gene assembly techniques resulted in the
      generation of a variety of therapeutic reagents such as vaccines, cancer
      treatment molecules and regenerative medicine precursors. With the advent of
      synthetic biology there is a growing need for precise and concerted assembly of
      multiple DNA fragments of various sizes, including chromosomes. In this article,
      we summarize the highlights of the recombinant DNA technology since its inception
      in the early 1970s, emphasizing on the most recent advances, and underscoring
      their principles, advantages and shortcomings. Current and prior cloning trends
      are discussed in the context of sequence requirements and scars left behind. Our
      opinion is that despite the remarkable progress that has enabled the generation
      and manipulation of very large DNA sequences, a better understanding of the
      cell's natural circuits is needed in order to fully exploit the current state-of
      the-art gene assembly technologies.

PMID- 22468856
TI  - Genetics of neuromuscular disorders.
AB  - Neuromuscular disorders affect the peripheral nervous system and muscle. The
      principle effect of neuromuscular disorders is therefore on the ability to
      perform voluntary movements. Neuromuscular disorders cause significant
      incapacity, including, at the most extreme, almost complete paralysis.
      Neuromuscular diseases include some of the most devastating disorders that
      afflict mankind, for example motor neuron disease. Neuromuscular diseases have
      onset any time from in utero until old age. They are most often genetic. The last
      25 years has been the golden age of genetics, with the disease genes responsible
      for many genetic neuromuscular disorders now identified. Neuromuscular disorders
      may be inherited as autosomal dominant, autosomal recessive, or X-linked traits.
      They may also result from mutations in mitochondrial DNA or from de novo
      mutations not present in the peripheral blood DNA of either parent. The high
      incidence of de novo mutation has been one of the surprises of the recent
      increase in information about the genetics of neuromuscular disorders. The
      disease burden imposed on families is enormous including decision making in
      relation to presymptomatic diagnosis for late onset neurodegenerative disorders
      and reproductive choices. Diagnostic molecular neurogenetics laboratories have
      been faced with an ever-increasing range of disease genes that could be tested
      for and usually a finite budget with which to perform the possible testing.
      Neurogenetics has moved from one known disease gene, the Duchenne muscular
      dystrophy gene in July 1987, to hundreds of disease genes in 2011. It can be
      anticipated that with the advent of next generation sequencing (NGS), most, if
      not all, causative genes will be identified in the next few years. Any type of
      mutation possible in human DNA has been shown to cause genetic neuromuscular
      disorders, including point mutations, small insertions and deletions, large
      deletions and duplications, repeat expansions or contraction and somatic
      mosaicism. The diagnostic laboratory therefore has to be capable of a large
      number of techniques in order to identify the different mutation types and
      requires highly skilled staff. Mutations causing neuromuscular disorders affect
      the largest human proteins for example titin and nebulin. Successful molecular
      diagnosis can make invasive and expensive diagnostic procedures such as muscle
      biopsy unnecessary. Molecular diagnosis is currently largely based on Sanger
      sequencing, which at most can sequence a small number of exons in one gene at a
      time. NGS techniques will facilitate molecular diagnostics, but not for all types
      of mutations. For example, NGS is not good at identifying repeat expansions or
      copy number variations. Currently, diagnostic molecular neurogenetics is focused
      on identifying the causative mutation(s) in a patient. In the future, the focus
      might move to prevention, by identifying carriers of recessive diseases before
      they have affected children. The pathobiology of many of the diseases remains
      obscure, as do factors affecting disease severity. The aim of this review is to
      describe molecular diagnosis of genetic neuromuscular disorders in the past, the
      present and speculate on the future.

PMID- 22468855
TI  - The chemical biology of S-nitrosothiols.
AB  - SIGNIFICANCE: S-nitrosothiol formation and protein S-nitrosation is an important
      nitric oxide (NO)-dependent signaling paradigm that is relevant to almost all
      aspects of cell biology, from proliferation, to homeostasis, to programmed cell
      death. However, the mechanisms by which S-nitrosothiols are formed are still
      largely unknown, and there are gaps of understanding between the known chemical
      biology of S-nitrosothiols and their reported functions. RECENT ADVANCES: This
      review attempts to describe the biological chemistry of S-nitrosation and to
      point out where the challenges lie in matching the known chemical biology of
      these compounds with their reported functions. The review will detail new
      discoveries concerning the mechanisms of the formation of S-nitrosothiols in
      biological systems. CRITICAL ISSUES: Although S-nitrosothiols may be formed with
      some degree of specificity on particular protein thiols, through un-catalyzed
      chemistry, and mechanisms for their degradation and redistribution are present,
      these processes are not sufficient to explain the vast array of specific and
      targeted responses of NO that have been attributed to S-nitrosation. Elements of
      catalysis have been discovered in the formation, distribution, and metabolism of
      S-nitrosothiols, but it is less clear whether these represent a specific network
      for targeted NO-dependent signaling. FUTURE DIRECTIONS: Much recent work has
      uncovered new targets for S-nitrosation through either targeted or proteome-wide
      approaches There is a need to understand which of these modifications represent
      concerted and targeted signaling processes and which is an inevitable consequence
      of living with NO. There is still much to be learned about how NO transduces
      signals in cells and the role played by protein S-nitrosation.

PMID- 22468857
TI  - CSF-1 signaling in macrophages: pleiotrophy through phosphotyrosine-based
      signaling pathways.
AB  - Colony stimulating factor-1 (CSF-1, also known as macrophage-colony stimulating
      factor, M-CSF) has long been known as the primary growth factor regulating
      survival, proliferation and differentiation of macrophages and other mononuclear
      phagocytic (MNP) lineage cells. CSF-1 was subsequently identified as a
      monocyte/macrophage chemokine, a capacity now recognized to be integral to many
      of the deleterious as well as positive roles of macrophages in development,
      homeostasis and disease. The pleiotrophic actions of CSF-1 are all transduced by
      its high affinity receptor, the CSF-1R, a receptor tyrosine kinase (RTK) and the
      cellular homologue of the v-fms oncoprotein. While the CSF-1R is the sole
      receptor for CSF-1, an alternative functional ligand for the receptor,
      interleukin-34 (IL-34), was recently identified. CSF-1-induced CSF-1R activation
      triggers autophosphorylation of several intracellular tyrosine residues, leading
      to initiation of an array of phosphotyrosine-based signaling cascades that
      mediate the wide variety of cellular responses to CSF-1. Dissecting the
      contributions of the different phosphorylated tyrosine motifs of the receptor to
      downstream signaling events in macrophages is not only important for our
      understanding of CSF-1R function, but also for the development of inhibitors to
      treat diseases where infiltrating macrophages contribute to their progression.
      This review will outline our current understanding of the CSF-1/CSF-1R signaling
      axis and describe how a novel macrophage cell line system, which allows
      examination of CSF-1R signaling in a mature macrophage context, is helping us to
      tease apart the diverse signaling pathways initiated by CSF-1R activation.

PMID- 22468858
TI  - Turning on and off the rotational oscillation of a single porphine molecule by
      molecular charge state.
AB  - The rotation dynamics of single magnesium porphine molecules on an ultrathin NaCl
      bilayer is investigated with low-temperature scanning tunneling microscopy and
      density functional theory calculations. It is observed that the rotational
      oscillation between two stable orientations can be turned on and off by the
      molecular charge state, which can be manipulated with the tunneling electrons.
      The features of the charge states and the mechanism of molecular rotational
      on/off state control are revealed at the atomic scale. The dependence of
      molecular orientation switching rate on the tunneling electron energy and the
      current density illustrates the underlying resonant tunneling excitation and
      single-electron process. The drive and control of molecular motion with tunneling
      electrons demonstrated in this study suggests a novel approach toward
      electronically controlled molecular rotors and motors.

PMID- 22468859
TI  - Quantitative analysis of powder mixtures by Raman spectrometry: the influence of
      particle size and its correction.
AB  - Particle size distribution and compactness have significant confounding effects
      on Raman signals of powder mixtures, which cannot be effectively modeled or
      corrected by traditional multivariate linear calibration methods such as partial
      least-squares (PLS), and therefore greatly deteriorate the predictive abilities
      of Raman calibration models for powder mixtures. The ability to obtain directly
      quantitative information from Raman signals of powder mixtures with varying
      particle size distribution and compactness is, therefore, of considerable
      interest. In this study, an advanced quantitative Raman calibration model was
      developed to explicitly account for the confounding effects of particle size
      distribution and compactness on Raman signals of powder mixtures. Under the
      theoretical guidance of the proposed Raman calibration model, an advanced dual
      calibration strategy was adopted to separate the Raman contributions caused by
      the changes in mass fractions of the constituents in powder mixtures from those
      induced by the variations in the physical properties of samples, and hence
      achieve accurate quantitative determination for powder mixture samples. The
      proposed Raman calibration model was applied to the quantitative analysis of
      backscatter Raman measurements of a proof-of-concept model system of powder
      mixtures consisting of barium nitrate and potassium chromate. The average
      relative prediction error of prediction obtained by the proposed Raman
      calibration model was less than one-third of the corresponding value of the best
      performing PLS model for mass fractions of barium nitrate in powder mixtures with
      variations in particle size distribution, as well as compactness.

PMID- 22468860
TI  - Disentangling the coil: modulation of conformational and dynamic properties by
      site-directed mutation in the non-native state of hen egg white lysozyme.
AB  - The conformational analysis of non-native states of proteins remains one of the
      most difficult problems in structural biology, because such states are
      represented by a superimposition of several states that are rapidly
      interconverting. Hence, model building of the conformational ensemble remains
      challenging, although many different biophysical observables can be determined in
      non-native states of proteins. Here, we present a comprehensive analysis of non
      native states of wild-type and mutant forms of the model protein lysozyme by
      nuclear magnetic resonance spectroscopy. Relaxation rates, chemical shifts,
      backbone and side chain coupling constants, residual dipolar couplings, diffusion
      rate constants, and small-angle scattering data merged with computational
      approaches, such as flexible meccano and ASTEROIDS, allow the description of the
      non-native state of hen egg white lysozyme in unprecedented detail.

PMID- 22468861
TI  - Premixed insulin aspart 30 (BIAsp 30) versus premixed human insulin 30 (BHI 30)
      in gestational diabetes mellitus: a randomized open-label controlled study.
AB  - A randomized, open-label, parallel study was conducted to assess the efficacy and
      safety of premixed insulin aspart 30 (biphasic insulin aspart [BIAsp] 30) in
      managing gestational diabetes mellitus (GDM). A total of 323 women with GDM
      registered at a single center in India were randomly assigned to receive 6 U of
      either BIAsp 30 (Group A) or premixed human insulin (biphasic human insulin [BHI]
      30; Group B) in a 1:1 ratio. Subjects performed home glucose monitoring and
      visited their care provider twice a month. The primary outcome was the degree of
      neonatal macrosomia (neonatal birth weight >90th percentile). Groups A and B were
      demographically comparable at study entry. Before labor onset, Groups A and B
      achieved similar degrees of fasting plasma glucose and postprandial plasma
      glucose control (92.97 +/- 14.44 vs. 95.43 +/- 18.96 and 127.59 +/- 28.99 vs.
      126.98 +/- 29.89, respectively; both p = NS). Neonatal macrosomia frequency was
      6.3% in Group A and 6.9% in Group B; however, this difference was not
      statistically significant. By last visit, the required insulin dose was
      significantly lower for Group A than Group B (19.83 +/- 15.75 IU vs. 26.34 +/-
      23.15 IU, respectively; p = 0.006). BIAsp 30 was noninferior to BHI 30, producing
      comparable fetal outcomes when administered during pregnancy. Based on final
      doses, BIAsp 30 may offer greater treat-to-target potential for pregnant women.

PMID- 22468863
TI  - Overexpression of urinary N-domain ACE in chronic kidney dysfunction in Wistar
      rats.
AB  - Local activation of the renin-angiotensin system (RAS) has been implicated in the
      pathogenesis of several renal disorders. In this study we investigated how
      chronic kidney disease (CKD) modulates RAS components in an experimental model.
      Male Wistar rats were divided into three groups: sham, nephrectomized, and
      nephrectomized receiving losartan. Chronic kidney disease animals presented
      decreased renal N-domain angiotensin-converting enzyme (ACE) activity but
      overexpression of N-domain ACE in urine. Remnant kidneys presented high
      angiotensin II levels. Losartan treatment increased urine and tissue ACE activity
      and tissue levels of angiotensins, mainly angiotensin (1-7), and improved renal
      and histopathologic parameters. Taken together, the authors' results indicate
      that pathophysiological changes due to CKD could lead to an increased expression
      of somatic and N-domain ACE, mainly the 65 kDa isoform, suggesting that this
      enzyme could be used as a biological urinary marker in CKD.

PMID- 22468862
TI  - Native chemical ligation of thioamide-containing peptides: development and
      application to the synthesis of labeled alpha-synuclein for misfolding studies.
AB  - Thioamide modifications of the peptide backbone are used to perturb secondary
      structure, to inhibit proteolysis, as photoswitches, and as spectroscopic labels.
      Thus far, their incorporation has been confined to single peptides synthesized on
      solid phase. We have generated thioamides in C-terminal thioesters or N-terminal
      Cys fragments and examined their compatibility with native chemical ligation
      conditions. Most sequence variants can be coupled in good yields with either TCEP
      or DTT as the reductant, though some byproducts are observed with prolonged TCEP
      incubations. Furthermore, we find that thioamides are compatible with
      thiazolidine protection of an N-terminal Cys, so that multiple ligations can be
      used to construct larger proteins. Since the acid-lability of the thioamide
      prohibits on-resin thioester synthesis using Boc chemistry, we devised a method
      for the synthesis of thioamide peptides with a masked C-terminal thioester that
      is revealed in situ. Finally, we have shown that thioamidous peptides can be
      coupled to expressed protein fragments to generate large proteins with backbone
      thioamide labels by synthesizing labeled versions of the amyloid protein alpha
      synuclein for protein folding studies. In a proof-of-principle experiment, we
      demonstrated that quenching of fluorescence by thioamides can be used to track
      conformational changes during aggregation of labeled alpha-synuclein.

PMID- 22468864
TI  - Trying something new: episode payments for cancer therapy.

PMID- 22468865
TI  - Are we winning the war on cancer?

PMID- 22468866
TI  - Putting value into practice.

PMID- 22468867
TI  - Targeted products yield most promising results.

PMID- 22468868
TI  - The truth about electronic health records.

PMID- 22468869
TI  - The great biomarker chase.

PMID- 22468870
TI  - The 4 pillars: foundation for care.

PMID- 22468871
TI  - Drug profiles.

PMID- 22468873
TI  - The economics of cancer care in the United States.

PMID- 22468874
TI  - Technologies behind biomarker discovery and development.

PMID- 22468875
TI  - Payer management of oncology gets serious.

PMID- 22468876
TI  - Unraveling the complexity of drug shortages.

PMID- 22468877
TI  - Benefits of two mitigation strategies for container vessels: cleaner engines and
      cleaner fuels.
AB  - Emissions from ocean-going vessels (OGVs) are a significant health concern for
      people near port communities. This paper reports the emission benefits for two
      mitigation strategies, cleaner engines and cleaner fuels, for a 2010 container
      vessel. In-use emissions were measured following International Organization for
      Standardization (ISO) protocols. The overall in-use nitrogen oxide (NO(x))
      emission factor was 16.1 +/- 0.1 gkW(-1) h(-1), lower than the Tier 1
      certification (17 gkW(-1) h(-1)) and significantly lower than the benchmark value
      of 18.7 gkW(-1) h(-1) commonly used for estimating emission inventories. The in
      use particulate matter (PM(2.5)) emission was 1.42 +/- 0.04 gkW(-1) h(-1) for
      heavy fuel oil (HFO) containing 2.51 wt % sulfur. Unimodal (~30 nm) and bimodal
      (~35 nm; ~75 nm) particle number size distributions (NSDs) were observed when the
      vessel operated on marine gas oil (MGO) and HFO, respectively. First-time
      emission measurements during fuel switching (required 24 nautical miles from
      coastline) showed that concentrations of sulfur dioxide (SO(2)) and particle NSD
      took ~55 min to reach steady-state when switching from MGO to HFO and ~84 min in
      the opposite direction. Therefore, if OGVs commence fuel change at the regulated
      boundary, then vessels can travel up to 90% of the distance to the port before
      steady-state values are re-established. The transient behavior follows a classic,
      nonlinear mixing function driven by the amount of fuel in day tank and the fuel
      consumption rate. Hence, to achieve the maximum benefits from a fuel change
      regulation, fuel switch boundary should be further increased to provide the
      intended benefits for the people living near the ports.

PMID- 22468878
TI  - Adverse perinatal outcomes after the February 27th 2010 Chilean earthquake.
AB  - OBJECTIVE: To investigate whether the February 27th earthquake exposition was
      associated to adverse perinatal outcomes in Chilean pregnant women. METHODS: We
      analyzed all deliveries occurred in 2009 (n = 3,609) and 2010 (n = 3,279) in a
      reference hospital in the area of the earthquake. Furthermore, we investigated
      pregnant women who gave birth between March 1st and December 31st 2010 (n =
      2,553) and we classified them according to timing of exposition. RESULTS: We
      found a 9% reduction in birth rate, but an increase in the rate of early preterm
      deliveries (<34 weeks), premature rupture of membranes (PROM), macrosomia, small
      for gestational age, and intrauterine growth restriction (IUGR) after the
      earthquake, in contrast to the previous year. Women exposed to the earthquake
      during her first trimester delivered smaller newborns (3,340 +/- 712 g v/s 3,426
      +/- 576 g respectively, p = 0.007) and were more likely diagnosed with early
      preterm delivery, preterm delivery (<37 weeks) and PROM but were less likely
      diagnosed with IUGR and late delivery (42 weeks, p < 0.05) compared to those
      exposed at third trimester. Accordingly, IUGR and preterm deliveries presented
      elevated healthcare costs. CONCLUSION: Natural disasters such as earthquakes are
      associated to adverse perinatal outcomes that impact negatively the entire
      maternal-neonatal healthcare system.

PMID- 22468879
TI  - Xanthosoma sagittifolium and Laportea aestuans: species used to prevent
      osteoporosis in Brazilian traditional medicine.
AB  - CONTEXT: Xanthosoma sagittifolium Schott. (Araceae) and Laportea aestuans (L.)
      Chew (Urticaceae) are two medicinal species used as food and to prevent and treat
      bone diseases, such as osteoporosis, in traditional Brazilian medicine.
      OBJECTIVE: To investigate the free calcium concentration and further support the
      traditional use of these species as medicine. MATERIALS AND METHODS: L. aestuans
      and X. sagittifolium leaves were dehydrated and cooked to evaluate the presence
      of free calcium. The total oxalate content was determined by heat digestion in
      H(2)SO(4), oxalate precipitation with CaCl(2) and permanganate titration.
      RESULTS: The calcium content found in L. aestuans was quite significant (638.00
      mg/100 g), whereas the fresh and cooked leaves of X. sagittifolium demonstrated a
      low content of calcium, at 273.17 and 369.81 mg/100 g, respectively. DISCUSSION
      AND CONCLUSION: The use of this species for the prevention and treatment of bone
      diseases is in agreement with the results of the free calcium (Ca(++)) analyses.
      Our data show that each species may be used as a health supplement in poor
      communities, provided that studies validate their safe use.

PMID- 22468880
TI  - Regulatory focus and work-related outcomes: a review and meta-analysis.
AB  - Regulatory focus theory (Higgins, 1997) has received growing attention in
      organizational psychology, necessitating a quantitative review that synthesizes
      its effects on important criteria. In addition, there is need for theoretical
      integration of regulatory focus theory with personality research. Theoretical
      integration is particularly relevant, since personality traits and dispositions
      are distal factors that are unlikely to have direct effects on work behaviors,
      yet they may have indirect effects via regulatory focus. The current meta
      analysis introduces an integrative framework in which the effects of personality
      on work behaviors are best understood when considered in conjunction with more
      proximal motivational processes such as regulatory focus. Using a distal-proximal
      approach, we identify personality antecedents and work-related consequences of
      regulatory foci in a framework that considers both general and work-specific
      regulatory foci as proximal motivational processes. We present meta-analytic
      results for relations of regulatory focus with its antecedents (approach and
      avoid temperaments, conscientiousness, openness to experience, agreeableness,
      self-esteem, and self-efficacy) and its consequences (work behaviors and
      attitudes). In addition to estimates of bivariate relationships, we support a
      meta-analytic path model in which distal personality traits relate to work
      behaviors via the mediating effects of general and work-specific regulatory
      focus. Results from tests of incremental and relative validity indicated that
      regulatory foci predict unique variance in work behaviors after controlling for
      established personality, motivation, and attitudinal predictors. Consistent with
      regulatory focus theory and our integrative theoretical framework, regulatory
      focus has meaningful relations with work outcomes and is not redundant with other
      individual difference variables.

PMID- 22468881
TI  - Gender differences in self-conscious emotional experience: a meta-analysis.
AB  - The self-conscious emotions (SCE) of guilt, shame, pride, and embarrassment are
      moral emotions, which motivate adherence to social norms and personal standards
      and emerge in early childhood following the development of self-awareness. Gender
      stereotypes of emotion maintain that women experience more guilt, shame, and
      embarrassment but that men experience more pride. To estimate the magnitude of
      gender differences in SCE experience and to determine the circumstances under
      which these gender differences vary, we meta-analyzed 697 effect sizes
      representing 236,304 individual ratings of SCE states and traits from 382 journal
      articles, dissertations, and unpublished data sets. Guilt (d = -0.27) and shame
      (d = -0.29) displayed small gender differences, whereas embarrassment (d = 
      0.08), authentic pride (d = -0.01), and hubristic pride (d = 0.09) showed gender
      similarities. Similar to previous findings of ethnic variations in gender
      differences in other psychological variables, gender differences in shame and
      guilt were significant only for White samples or samples with unspecified
      ethnicity. We found larger gender gaps in shame with trait (vs. state) scales,
      and in guilt and shame with situation- and scenario-based (vs. adjective- and
      statement-based) items, consistent with predictions that such scales and items
      tend to tap into global, nonspecific assessments of the self and thus reflect
      self-stereotyping and gender role assimilative effects. Gender differences in SCE
      about domains such as the body, sex, and food or eating tended to be larger than
      gender differences in SCE about other domains. These findings contribute to the
      literature demonstrating that blanket stereotypes about women's greater
      emotionality are inaccurate.

PMID- 22468882
TI  - Size dependence of the adsorption energy of CO on metal nanoparticles: a DFT
      search for the minimum value.
AB  - With a density functional theory method, we studied computationally the size
      dependence of adsorption properties of metal nanoparticles for CO as a probe on
      Pd(n) clusters with n = 13-116 atoms. For large particles, the values slowly
      decrease with cluster size from the asymptotic value for an (ideal) infinite
      surface. For clusters of 13-25 atoms, starting well above the asymptotic value,
      the adsorption energies drop quite steeply with increasing cluster size. These
      opposite trends meet in an intermediate size range, for clusters of 30-50 atoms,
      yielding the lowest adsorption energies. These computational results help to
      resolve a controversy on the size-dependent behavior of adsorption energies of
      metal nanoparticles.

PMID- 22468883
TI  - Hypoxia-inducible factor 1-alpha-AA-modified bone marrow stem cells protect PC12
      cells from hypoxia-induced apoptosis, partially through VEGF/PI3K/Akt/FoxO1
      pathway.
AB  - Bone marrow stem cells (BMSCs) have been shown to improve neurological function
      recovery in cerebral ischemia. Hypoxia-inducible factor-1 (HIF-1) alpha-AA is a
      more stable mutant form of HIF-1alpha, which is a crucial oxygen-sensitive
      regulator. To investigate the protective effects of HIF-1alpha-AA-modified BMSCs
      on neuron survival in cerebral ischemia models, we co-cultured HIF-1alpha-AA
      modified BMSCs with neuron-like cells (PC12 cells) and observed a significant
      increase in the release of vascular endothelial growth factor (VEGF) from BMSCs,
      the decreased PC12 cell apoptosis, and the upregulation of Survivin expression
      reduced by hypoxia in PC12 cells compared to enhanced green fluorescent protein
      (EGFP) BMSCs. In addition, to explore whether VEGF secreted by HIF-1alpha-AA
      modified BMSCs plays an important role in preventing hypoxia-induced apoptosis
      and the possible mechanism involved, exogenous VEGF were applied and the similar
      protective effects on PC12 cells were observed in vitro. Furthermore, hypoxia
      reduced the expression of phosphorylated Akt and phosphorylated FoxO1, whereas
      the administration of VEGF reversed these changes. Transfection of FoxO1 H215R, a
      DNA-binding mutant, abrogated the inhibitory ability on Survivin promoter
      activity, whereas FoxO1 AAA, the active form of FoxO1, presented further
      repression on Survivin promoter, indicating that FoxO1 directly binds on Survivin
      promoter as a transcriptional repressor and that phosphorylation status of FoxO1
      affects its inhibition on the Survivin promoter. Transplantation of HIF-1alpha-AA
      modified BMSCs after cerebral ischemia in vivo sufficiently reduced neurons
      apoptosis, decreased cerebral infarction volume, and induced a significant
      improvement on the modified neurological severity score compared to the EGFP
      BMSCs group. In conclusion, HIF-1alpha-AA-modified MSCs showed an obvious
      protective effect on neuron-like cells or neuron after ischemia in vitro and in
      vivo, at least in part, through the VEGF/PI3K/Akt/FoxO1 pathway.

PMID- 22468885
TI  - From the land of Greece to the lands of Titan.

PMID- 22468884
TI  - Lateralized response of dynorphin a peptide levels after traumatic brain injury.
AB  - Traumatic brain injury (TBI) induces a cascade of primary and secondary events
      resulting in impairment of neuronal networks that eventually determines clinical
      outcome. The dynorphins, endogenous opioid peptides, have been implicated in
      secondary injury and neurodegeneration in rodent and human brain. To gain insight
      into the role of dynorphins in the brain's response to trauma, we analyzed short
      term (1-day) and long-term (7-day) changes in dynorphin A (Dyn A) levels in the
      frontal cortex, hippocampus, and striatum, induced by unilateral left-side or
      right-side cortical TBI in mice. The effects of TBI were significantly different
      from those of sham surgery (Sham), while the sham surgery also produced
      noticeable effects. Both sham and TBI induced short-term changes and long-term
      changes in all three regions. Two types of responses were generally observed. In
      the hippocampus, Dyn A levels were predominantly altered ipsilateral to the
      injury. In the striatum and frontal cortex, injury to the right (R) hemisphere
      affected Dyn A levels to a greater extent than that seen in the left (L)
      hemisphere. The R-TBI but not L-TBI produced Dyn A changes in the striatum and
      frontal cortex at 7 days after injury. Effects of the R-side injury were similar
      in the two hemispheres. In naive animals, Dyn A was symmetrically distributed
      between the two hemispheres. Thus, trauma may reveal a lateralization in the
      mechanism mediating the response of Dyn A-expressing neuronal networks in the
      brain. These networks may differentially mediate effects of left and right brain
      injury on lateralized brain functions.

PMID- 22468886
TI  - Planning for Mars returned sample science: final report of the MSR End-to-End
      International Science Analysis Group (E2E-iSAG).

PMID- 22468888
TI  - A combinatorial approach to biochemical space: description and application to the
      redox distribution of metabolism.
AB  - Redox chemistry is central to life on Earth. It is well known that life uses
      redox chemistry to capture energy from environmental chemical energy gradients.
      Here, we propose that a second use of redox chemistry, related to building
      biomass from environmental carbon, is equally important to life. We apply a
      method based on chemical structure to evaluate the redox range of different
      groups of terrestrial biochemicals, and find that they are consistently of
      intermediate redox range. We hypothesize the common intermediate range is related
      to the chemical space required for the selection of a consistent set of
      metabolites. We apply a computational method to show that the redox range of the
      chemical space shows the same restricted redox range as the biochemicals that are
      selected from that space. By contrast, the carbon from which life is composed is
      available in the environment only as fully oxidized or reduced species. We
      therefore argue that redox chemistry is essential to life for assembling
      biochemicals for biomass building. This biomass-building reason for life to
      require redox chemistry is in addition (and in contrast) to life's use of redox
      chemistry to capture energy. Life's use of redox chemistry for biomass capture
      will generate chemical by-products-that is, biosignature gases-that are not in
      redox equilibrium with life's environment. These potential biosignature gases may
      differ from energy-capture redox biosignatures.

PMID- 22468887
TI  - Impact disruption and recovery of the deep subsurface biosphere.
AB  - Although a large fraction of the world's biomass resides in the subsurface, there
      has been no study of the effects of catastrophic disturbance on the deep
      biosphere and the rate of its subsequent recovery. We carried out an
      investigation of the microbiology of a 1.76 km drill core obtained from the ~35
      million-year-old Chesapeake Bay impact structure, USA, with robust contamination
      control. Microbial enumerations displayed a logarithmic downward decline, but the
      different gradient, when compared to previously studied sites, and the scatter of
      the data are consistent with a microbiota influenced by the geological
      disturbances caused by the impact. Microbial abundance is low in buried crater
      fill, ocean-resurge, and avalanche deposits despite the presence of redox couples
      for growth. Coupled with the low hydraulic conductivity, the data suggest the
      microbial community has not yet recovered from the impact ~35 million years ago.
      Microbial enumerations, molecular analysis of microbial enrichment cultures, and
      geochemical analysis showed recolonization of a deep region of impact-fractured
      rock that was heated to above the upper temperature limit for life at the time of
      impact. These results show how, by fracturing subsurface rocks, impacts can
      extend the depth of the biosphere. This phenomenon would have provided deep
      refugia for life on the more heavily bombarded early Earth, and it shows that the
      deeply fractured regions of impact craters are promising targets to study the
      past and present habitability of Mars.

PMID- 22468889
TI  - Studying light propagation in self-assembled hybrid photonic-plasmonic crystals
      by fourier microscopy.
AB  - Hybrid metallodielectric systems where dielectric components are combined with
      metals supporting surface plasmons are able to spatially redistribute the
      electromagnetic field intensity within its volume through hybrid photonic
      plasmonic modes. While most of the work done recently in this kind of systems has
      been focused on the way such redistribution takes place and how light couples to
      or is emitted from such samples, the way light propagation takes place has not
      been studied in depth. Here we consider light propagation in hybrid systems
      fabricated by self-assembly methods measuring their equifrequency surfaces both
      in reflection and emission configurations. Comparing spectroscopic measurements
      with equifrequency surfaces provides a deeper insight into the way light
      propagates in these structures, showing the possibilities they may present for
      several applications.

PMID- 22468890
TI  - Identifying and characterizing promiscuous targets: implications for virtual
      screening.
AB  - INTRODUCTION: Ligand-based shape matching approaches have become established as
      important and popular virtual screening (VS) techniques. However, despite their
      relative success, the question of how to best choose the initial query compounds
      and their conformations remains largely unsolved. This issue gains importance
      when dealing with promiscuous targets, that is, proteins that bind multiple
      ligand scaffold families in one or more binding site. Conventional shape matching
      VS approaches assume that there is only one binding mode for a given protein
      target. This may be true for some targets, but it is certainly not true in all
      cases. Several recent studies have shown that some protein targets bind to
      different ligands in different ways. AREAS COVERED: The authors discuss the
      concept of promiscuity in the context of virtual drug screening, and present and
      analyze several examples of promiscuous targets. The article also reports on the
      impact of the query conformation on the performance of shape-based VS and the
      potential to improve VS performance by using consensus shape clustering
      techniques. EXPERT OPINION: The notion of polypharmacology is becoming highly
      relevant in drug discovery. Understanding and exploiting promiscuity present
      challenges and opportunities for drug discovery endeavors. The examples of
      promiscuity presented here suggest that promiscuous targets and ligands are much
      more common than previously assumed, and this should be taken into account in
      practical VS protocols. Although some progress has been made, there is a need to
      develop more sophisticated computational techniques and protocols that can
      identify and characterize promiscuous targets on a genomic scale.

PMID- 22468891
TI  - Advances in the identification of gamma-secretase inhibitors for the treatment of
      Alzheimer's disease.
AB  - INTRODUCTION: In an attempt of altering the natural history of Alzheimer's
      disease (AD), several compounds have been developed with the aim of inhibiting
      gamma-secretase, the enzymatic complex generating beta-amyloid (Abeta) peptides
      (Abeta(1 - 40) and Abeta(1 - 42)), from amyloid precursor protein (APP). APP is
      believed to be involved in the pathophysiological cascade of AD. AREAS COVERED:
      This article briefly reviews the profile of gamma-secretase inhibitors that have
      reached the clinic. The paper reviews studies from the primary English literature
      on gamma-secretase inhibitors published before November 2011, searching through
      the PubMed database of NCBI by author and the following keywords: drugs targeting
      beta-amyloid, gamma-secretase inhibitors, dementia syndromes and Alzheimer's
      disease. EXPERT OPINION: Studies in both transgenic and non-transgenic animal
      models of AD have indicated that gamma-secretase inhibitors, administered by the
      oral route, are able to lower brain Abeta concentrations. However, scanty data
      are available on the effects of these compounds on brain Abeta deposition after
      prolonged administration. gamma-Secretase inhibitors may cause significant
      toxicity in experimental animals and in humans believed to be associated with the
      inhibition of the cleavage of Notch, a transmembrane receptor involved in
      regulating cell-fate decisions. Unfortunately, two large Phase III clinical
      trials of semagacestat in mild-to-moderate AD patients were prematurely
      interrupted because of the observation of a detrimental cognitive and functional
      effects of the drug, possibly due to its lack of selectivity on APP processing.
      New APP-selective gamma-secretase inhibitors are being developed with the hope of
      overcoming the previous setbacks.

PMID- 22468892
TI  - Improving potencies and properties of CD4 down-modulating CADA analogs.
AB  - INTRODUCTION: CADA is a synthetic small molecule that inhibits HIV replication in
      cell cultures through down-modulating cell surface CD4 by inhibiting
      cotranslational translocation of nascent CD4 across the ER membrane in a signal
      sequence-specific manner. Analogs have been prepared mainly to increase potency
      and investigate the mechanism of action. AREAS COVERED: This article reviews
      progress on discovery of more potent CADA analogs, including symmetrical and
      unsymmetrical compounds, as well as fluorescent derivatives. The article also
      discusses some properties of CADA and a more potent analog (KKD023) that are
      relevant to drug development, including aqueous solubility, permeability,
      metabolism and oral bioavailability. EXPERT OPINION: Further studies on CADA
      analogs should focus on improving both potency and drug-like properties, and on
      elucidating the detailed mechanism of action. Solubility and permeability may be
      improved by reducing molecular weight, decreasing molecular flexibility and
      symmetry, or by a prodrug approach inducing active transport. Identifying the
      molecular mechanism of CD4 down-modulation may aid in assessing potential side
      effects of such immunomodulatory/anti-HIV drugs, and it could potentially lead to
      a general approach to designing drugs for specifically down-modulating other cell
      surface proteins.

PMID- 22468893
TI  - Psoriasis drug discovery: methods for evaluation of potential drug candidates.
AB  - INTRODUCTION: Psoriasis is a complex disease with several clinical subtypes, as
      well as variations in body location and severity. Many patients suffering from
      psoriasis now benefit from the increased understanding of the pathogenesis of the
      disease, which in turn drives translational efforts to test new therapeutic
      concepts in the clinic. However, a multitude of treatment options is currently
      needed to satisfy patient needs. AREAS COVERED: This review describes the drug
      discovery platform in relation to psoriasis with special emphasis on how the
      major disease mechanisms of psoriasis can be studied in experimental in vitro and
      in vivo settings. The value of using humanized models and experimental clinical
      studies is highlighted. EXPERT OPINION: The successful development of novel
      therapies requires a translational approach to develop and implement the best
      preclinical and experimental clinical models and analytical tools that capture
      the various biological aspects of the disease. There is a need for more advanced
      in vitro skin models that contain the relevant cellular constituents as well as a
      need for careful validation of relevant in vivo models for psoriasis.

PMID- 22468894
TI  - The emerging role of plasma lipidomics in cardiovascular drug discovery.
AB  - INTRODUCTION: With the rising global incidence of cardiovascular disease, the
      challenge for the pharmaceutical industry is to identify novel biomarkers that
      will allow not only for the development of the next generation of cardiometabolic
      therapeutics, but also to serve as a sensitive mechanism to monitor and predict
      drug efficacy and potential toxicity. The advent of an 'omics' (systems
      biological) approach has vast implications for future disease treatment and
      prevention. Lipidomics is the latest addition to the 'omics' family and is
      rapidly gaining attention due to the technological improvements in mass
      spectrometry, allowing for the characterization of large number of lipids (and
      their respective subclasses) in a short amount of time with relatively minimal
      preparation. AREAS COVERED: The authors discuss the various techniques involved
      in plasma lipidomics as well as outline the role that lipidomics will play in
      phenotyping disease processes and corresponding therapeutic strategies. The
      article was formed through comprehensive Medline search of relevant publications
      in this area. EXPERT OPINION: Despite the wealth of data that will emerge
      regarding the various lipid-molecular interactions and the functions of lipids
      within cells, a major challenge will be the parallel emergence of novel
      bioinformatics platforms in order to integrate this enormous data set with
      information generated from the emerging fields of genomics and proteomic
      analysis. Despite these challenges, lipidomics is likely to result in the
      reclassification of diseases from a molecular perspective and play a key role the
      eventuation of personalized medicine.

PMID- 22468895
TI  - The preclinical discovery of bacterial therapy for the treatment of metastatic
      cancer with unique advantages.
AB  - INTRODUCTION: The potential of bacteria as therapeutics for cancer has a long
      history, dating at least as far back as the early 19(th) Century. Bacteria have a
      large genome that can be manipulated in order to target and eradicate tumors.
      Many types of bacteria have been shown to target tumors but most are obligate
      anaerobes whose growth is confined to the necrotic parts of tumors, thereby
      limiting their efficacy. Salmonella, on the other hand, are facultative aerobes
      that can grow aerobically or anaerobically and, therefore, grow on viable tumor
      tissue as well as necrotic tissue. AREAS COVERED: The article focuses on the
      double amino-acid auxotrophs of Salmonella typhimurium. These auxotrophs, which
      have no attenuating mutations and can grow in both viable and necrotic areas of
      tumors but not normal tissue, have shown particular effectiveness in mouse models
      of metastatic cancer. The approach described here is a significant improvement
      over previous bacterial tumor-therapy strategies which must be combined with
      toxic chemotherapy in order to be effective. This review uniquely discusses the
      critical points to optimally engineer Salmonella typhimurium for cancer therapy.
      EXPERT OPINION: Bacterial therapy offers significant advantages over chemical or
      biological drugs or oncolytic viruses. Of these types of bacterial therapy,
      bacteria that can grow in both viable and necrotic areas of the tumors without
      growing in normal tissue hold the greatest promise in the treatment of cancer.
      Salmonella typhimurium shows much promise for this paradigm.

PMID- 22468896
TI  - Rodent models for the preclinical evaluation of drugs suitable for
      pharmacological intervention in aging.
AB  - INTRODUCTION: There is a growing scientific and public interest in the
      development of new antiaging drugs for the purposes of extending mean and/or
      maximum life span, maintaining normal physiological function, and alleviating the
      onset and severity of age-associated diseases. This review looks at the current
      screening approaches used to evaluate the efficacy of such compounds, with a
      particular focus on those that extend life span. AREAS COVERED: This article
      reviews the current preclinical approaches for assessing longevity therapy
      including the assessment of antiaging drugs (aging reversal) and geroprotectors
      (drugs that prevent premature aging and/or slowdown or postpone aging). This
      article also discusses the methods and the importance in evaluating the
      anticarcinogenic potential and safety of antitumor drugs. EXPERT OPINION: Based
      on more than 30 years of experience in the field, the authors believe that the
      standard testing protocols for antiaging drugs should include the simultaneous
      evaluation of the drug's safety, as well as its antitumor and anticarcinogenic
      activity potential. The authors also believe that the principles of international
      programs for the expert critical evaluation of pharmacological interventions
      should be created to improve the range of antiaging interventions available for
      human studies.

PMID- 22468898
TI  - Functional assembly of aptamer binding sites by single-molecule cut-and-paste.
AB  - Bottom up assembly of functional molecular ensembles with novel properties
      emerging from composition and arrangement of its constituents is a prime goal of
      nanotechnology. By single-molecule cut-and-paste we assembled binding sites for
      malachite green in a molecule-by-molecule assembly process from the two halves of
      a split aptamer. We show that only a perfectly joined binding site immobilizes
      the fluorophore and enhances the fluorescence quantum yield by several orders of
      magnitude. To corroborate the robustness of this approach we produced a
      micrometer-sized structure consisting of more than 500 reconstituted binding
      sites. To the best of our knowledge, this is the first demonstration of one by
      one bottom up functional biomolecular assembly.

PMID- 22468897
TI  - Effects of divalproex on smoking cue reactivity and cessation outcomes among
      smokers achieving initial abstinence.
AB  - Divalproex, a GABA agonist, may be a useful agent in the treatment of tobacco
      dependence. Cue reactivity assessment paradigms are ideally suited to explore
      basic mechanisms underlying the pharmacological effects of medications that
      purport to have efficacy for smoking cessation. Our primary goal in the current
      study was to examine the effects of divalproex on in-treatment reactivity to
      smoking-relevant and affective cues, and to determine if these reactions were
      predictive of posttreatment smoking behavior. There were 120 nicotine dependent
      smokers enrolled in an 8-week double-blind clinical trial and randomly assigned
      to either divalproex or placebo conditions. Of these, 72 smokers (60% female) who
      achieved a minimal level of abstinence underwent an in-treatment cue reactivity
      assessment. Contrary to expectations, divalproex was associated with greater
      craving and arousal during smoking cue presentation. Divalproex also inhibited
      cardiovascular response to pleasant cues. Although no significant differences in
      cessation-related outcomes between divalproex- and placebo-treated participants
      were observed, cue-elicited craving to smoke predicted end-of-treatment and
      posttreatment smoking rates. These findings suggest that in-treatment cue
      reactivity assessment may proactively and dynamically inform ongoing treatment as
      well as provide a tool for screening potential medications for smoking cessation.

PMID- 22468899
TI  - Efficient exciton transport between strongly quantum-confined silicon quantum
      dots.
AB  - Many-body Green function analysis and first-order perturbation theory are used to
      quantify the influence of size, surface reconstruction, and surface treatment on
      exciton transport between small silicon quantum dots. Competing radiative
      processes are also considered in order to determine how exciton transport
      efficiency is influenced. The analysis shows that quantum confinement causes
      small (~1 nm) Si quantum dots to exhibit exciton transport efficiencies far
      exceeding that of their larger counterparts for the same center-to-center
      separation. This surprising result offers the prospect of designing assemblies of
      quantum dots through which excitons can travel for long distances, a game
      changing paradigm shift for next-generation solar energy harvesting. We also find
      that surface reconstruction significantly influences the absorption cross section
      and leads to a large reduction in both transport rate and efficiency. Further,
      exciton transport efficiency is higher for hydrogen-passivated dots as compared
      with those terminated with more electronegative ligands, a result not predicted
      by Forster theory.

PMID- 22468900
TI  - Nitric oxide and pro-inflammatory cytokine serum levels in postmenopausal women
      with the metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome (METS) increases after the menopause which may
      enhance cardiovascular risk in part explained by a pro-inflammatory state.
      OBJECTIVE: Measure nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and
      interleukin 6 (IL-6) serum levels in postmenopausal women with and without the
      METS (Adult Treatment Panel III criteria). METHODS: Analyte levels were compared
      among those with and without the syndrome and each of its diagnostic components.
      Rho Spearman coefficients were also calculated to determine correlations between
      analyte levels and various numeric variables. RESULTS: Median age of all studied
      women (n = 88) was 54.4 years, 62.5% had abdominal obesity, 14.8% hyperglycemia,
      59.1% high triglycerides (TG) and 44.3% hypertension. Women with the METS (n =
      44) displayed higher body mass index values and higher rates of abdominal
      obesity, hyperglycemia, hypertriglyceridemia, hypertension and low HDL-C levels.
      Median NO and IL-6 levels were significantly higher in women with the METS as
      compared to controls (p < 0.05). Independent of presenting the METS, analytes
      were higher in those displaying abdominal obesity (IL-6), hypertension (IL-6 and
      TNF-alpha) and more METS diagnostic criteria and abnormal HDL-C, TG and glucose
      levels (NO). Both cytokines positively correlated with the number of METS
      criteria, age and time since menopause, IL-6 positively with waist circumference
      and TNF-alpha positively with blood pressure levels. NO levels inversely
      correlated with HDL-C values and positively with the number of METS criteria,
      glucose, and TG levels; correlation with the latter being the highest (r2 = 0.65,
      p = 0.0001). CONCLUSION: Postmenopausal women with the METS displayed higher IL-6
      and NO levels, with significant correlations found between studied analytes and
      some of the components of the syndrome.

PMID- 22468901
TI  - Maternal serum ferritin at 11- to 13-week gestation in spontaneous early preterm
      delivery.
AB  - OBJECTIVE: To examine the potential value of maternal serum level of ferritin in
      the first trimester of pregnancy in the prediction of spontaneous early preterm
      delivery. METHODS: Maternal serum concentration of ferritin at 11-13-week
      gestation was measured in a case-control study of singleton pregnancies
      delivering phenotypically normal neonates, including 30 cases with spontaneous
      delivery before 34 weeks and 90 matched controls delivering after 37 weeks. The
      median multiple of the median (MoM) serum ferritin in the two outcome groups was
      compared. RESULTS: The median serum ferritin MoM was not significantly different
      in the spontaneous early preterm delivery group compared with the term delivery
      group (1.143, interquartile range [IQR] 0.578-2.383 vs. 1.059, IQR 0.641-1.644, p
      = 0.725). CONCLUSIONS: Measurement of maternal serum ferritin at 11-13 weeks is
      unlikely to be useful in screening for spontaneous early preterm delivery.

PMID- 22468902
TI  - Synchrotron infrared measurements of protein phosphorylation in living single
      PC12 cells during neuronal differentiation.
AB  - Protein phosphorylation is a post-translational modification that is essential
      for the regulation of many important cellular activities, including proliferation
      and differentiation. Current techniques for detecting protein phosphorylation in
      single cells often involve the use of fluorescence markers, such as antibodies or
      genetically expressed proteins. In contrast, infrared spectroscopy is a label
      free and noninvasive analytical technique that can monitor the intrinsic
      vibrational signatures of chemical bonds. Here, we provide direct evidence that
      protein phosphorylation in individual living mammalian cells can be measured with
      synchrotron radiation-based Fourier transform-infrared (SR-FT-IR)
      spectromicroscopy. We show that PC12 cells stimulated with nerve growth factor
      (NGF) exhibit statistically significant temporal variations in specific spectral
      features, correlating with changes in protein phosphorylation levels and the
      subsequent development of neuron-like phenotypes in the cells. The spectral
      phosphorylation markers were confirmed by bimodal (FT-IR/fluorescence) imaging of
      fluorescently marked PC12 cells with sustained protein phosphorylation activity.
      Our results open up new possibilities for the label-free real-time monitoring of
      protein phosphorylation inside cells. Furthermore, the multimolecule sensitivity
      of this technique will be useful for unraveling the associated molecular changes
      during cellular signaling and response processes.

PMID- 22468903
TI  - Approaches for obtaining accurate rate constants for hydrogen abstraction by a
      chlorine atom.
AB  - We have assessed computational methodologies for calculating the rate constants
      for hydrogen abstraction by Cl(*) for a selection of 12 reactions. For the
      conventional approach of calculating higher-level [B2K-PLYP/aug'-cc
      pV[(T+d),(Q+d)]Z] single-point energies at lower-level [BH&H-LYP/6-31+G(d,p)]
      stationary points, large deviations from experimental rate constants are found in
      a number of cases in which the activation energy is very low. These discrepancies
      are due largely to deviations in the calculated activation energies and can be
      further traced to the inability of the low level to adequately locate the
      transition structures. We have examined several alternative approaches for
      calculating rate constants, namely, IRCmax, IRCmax at 0 K (ZK-IRCmax, with zero
      point vibration energies (ZPVEs) incorporated), variational transition-state
      theory (VTST), and VTST with the inclusion of an Eckart tunneling correction
      (VTST+E). We find that the low level gives reasonable values for the ZPVEs and
      thermal enthalpy and entropy corrections that are required in such approaches.
      While the VTST+E approach yields the closest agreement with experimental rate
      constants for the systems considered, we find that the simpler IRCmax approach
      gives adequate values and is able to avoid the major shortcomings of the
      conventional approach in a cost-effective manner.

PMID- 22468904
TI  - Effect of formulation compositions on niosomal preparations.
AB  - This study was aimed to investigate the effects of molar ratio of cholesterol to
      Span 60 and stabilizers (Solutol HS 15 or dicetyl phosphate (DCP)) on the
      entrapment of methylene blue, a model hydrophilic drug. The niosomes were
      prepared by the film hydration method and characterized for drug entrapment
      efficiency (EE), vesicle size, zeta potential and thermal properties of niosomal
      membrane. It was found that niosomal vesicles possessed median diameter ranging
      from 0.35 to 1.85 MUm. The niosomes that were formulated with lower molar ratios
      of cholesterol to Span 60 of 0.33 and 0.50 produced significantly higher EE with
      both stabilizers when compared to cholesterol to Span 60 molar ratios of 1.0 and
      above (p < 0.05). The EE of niosomes stabilized with DCP was significantly higher
      (p < 0.05) than those prepared with Solutol HS 15 except at a molar ratio of
      cholesterol to Span 60 of 0.33. In conclusion, with low molar ratios of
      cholesterol to Span 60, more drugs could be entrapped within the niosomes
      regardless of the type of stabilizers. Furthermore, EE and median diameter of
      niosomes containing DCP were higher than those stabilized with Solutol HS 15.

PMID- 22468905
TI  - Atrial electromechanical coupling interval and P-wave dispersion in patients with
      white coat hypertension.
AB  - BACKGROUND: The aim of our study was to investigate the effect of white coat
      hypertension (WCH) to atrial conduction abnormalities by electrocardiographic P
      wave analysis and echocardiographic electromechanical coupling (EMC) interval
      measurement. METHODS: The study consisted of sex-, age-, and body mass index
      matched 24 patients with WCH, 24 patients with sustained hypertension (SH), and
      24 subjects with normotension (NT). The difference between the maximum (Pmax) and
      minimum P-wave durations on 12-lead electrocardiography was defined as P-wave
      dispersion (PD). Intra- and inter-atrial EMC were measured by tissue Doppler
      imaging. RESULTS: Pmax and PD of subjects with WCH were significantly higher than
      those of normotensives and lower than those of patients with SH. Inter-atrial EMC
      and left atrial EMC values of WCH group were intermediate between NT and SH
      groups. There was a significant correlation between left atrial diameter, PD,
      Pmax, left ventricle mass index, left atrial EMC, and inter-atrial EMC.
      CONCLUSION: White coat hypertension is an intermediate group between SH and NT in
      terms of atrial electromechanical abnormalities which may be associated with the
      risk of atrial fibrillation.

PMID- 22468906
TI  - Harvesting photons to kill microbes: ES&T's top environmental technology article
      2011.

PMID- 22468907
TI  - Predictors of patient cognitive therapy skills and symptom change in two
      randomized clinical trials: the role of therapist adherence and the therapeutic
      alliance.
AB  - OBJECTIVE: Previous research has found that therapist adherence to concrete,
      problem-focused cognitive therapy (CT) techniques predicts depressive symptom
      change (e.g., Feeley, DeRubeis, & Gelfand, 1999). More recently, Strunk,
      DeRubeis, Chui, and Alvarez (2007) demonstrated that in-session evidence of
      patients' use of CT skills was related to a lower rate of relapse in the year
      following CT for depression. The current investigation attempts to integrate and
      extend these findings within 2 separate samples of patients and therapists.
      METHOD: Drawing from the CT samples (N = 105, mean age = 40 years, female = 62%,
      White = 82%) of 2 published randomized clinical trials of depression treatment,
      we conducted analyses to examine whether therapist adherence to concrete CT
      techniques (Collaborative Study Psychotherapy Rating Scale) and the quality of
      the therapeutic alliance (Working Alliance Inventory) predict patients' use of CT
      skills (Performance of Cognitive Therapy Strategies) and subsequent Beck
      Depression Inventory symptom change. RESULTS: Results indicated a differential
      pattern of prediction in the 2 samples. In one, CT techniques exhibited a
      stronger association with patient CT skills and symptom change than did the
      alliance, whereas the reverse pattern emerged in the second sample. A baseline
      symptom severity * CT techniques interaction indicated that between-study
      differences in intake depression severity might in part explain the process
      outcome differences. CONCLUSIONS: The present findings suggest that the nature of
      the therapy sample examined may moderate process-outcome findings in
      psychotherapy research. The implications of these results and directions for
      future research are discussed.

PMID- 22468908
TI  - Therapeutic alliance in telephone-administered cognitive-behavioral therapy for
      hematopoietic stem cell transplant survivors.
AB  - OBJECTIVE: A strong therapeutic alliance has been found to predict
      psychotherapeutic treatment success across a variety of therapeutic modalities
      and patient populations. However, only a few studies have examined therapeutic
      alliance as a predictor of psychotherapy outcome among cancer survivors, and none
      have examined this relation in telephone-administered cognitive-behavioral
      therapy (T-CBT). This study evaluated the extent to which therapeutic alliance
      affected psychotherapy outcomes in survivors of hematopoietic stem cell
      transplantation (HSCT), a treatment for some cancers. METHOD: Forty-six patients
      enrolled in a randomized clinical trial of T-CBT for posttraumatic stress
      disorder (PTSD) completed a baseline assessment (including self-report measures
      of PTSD symptoms, depression, and general distress), 10 individual T-CBT
      sessions, and follow-up assessments at 6, 9, and 12 months post-baseline.
      Therapeutic alliance was assessed after the 3rd T-CBT session with the Working
      Alliance Inventory, which yields overall and subscale (task, bond, and goal)
      scores. RESULTS: Analyses revealed that higher total therapeutic alliance scores
      prospectively predicted decreased depressive symptomatology; higher task scores
      predicted decreased overall distress, depressive symptomatology, symptoms of re
      experiencing, and avoidance; and higher bond scores predicted decreased
      depressive symptomatology and symptoms of re-experiencing. CONCLUSIONS: These
      results suggest that assessments of therapeutic alliance should be incorporated
      into routine clinical care, and therapeutic alliance should be specifically
      cultivated in interventions to maximize psychotherapeutic benefits involving
      vulnerable populations such as cancer survivors.

PMID- 22468909
TI  - Refinement of a brief anxiety sensitivity reduction intervention.
AB  - OBJECTIVE: Anxiety disorders are the most prevalent psychiatric disorders in the
      United States and result in substantial burden to the individual and society.
      Although effective treatments for anxiety disorders have been developed, there
      has been substantially less focus on interventions aimed at the amelioration of
      anxiety-related risk and maintenance factors. Anxiety sensitivity (AS) is a well
      established, malleable risk and maintenance factor for panic disorder and other
      psychopathology. The aim of the current investigation was to enhance the efficacy
      of AS treatment through the refinement of a previously validated intervention.
      METHOD: This 1-session intervention utilized psychoeducation and interoceptive
      exposure to target AS and was compared with a health-focused control intervention
      among a nontreatment seeking sample (N = 104) of individuals with elevated AS.
      RESULTS: Study findings indicate that the active treatment group demonstrated
      significantly greater reductions in AS than the control group at posttreatment
      and across the 1-month study period. These treatment gains were seen across the
      ASI subscales. A Month 6 follow-up assessment indicated that the treatment group
      retained the majority of their AS reduction, whereas the control group retained
      their elevated AS scores. The intervention responses of participants meeting Axis
      I diagnostic criteria did not differ from the responses of those without a
      current diagnosis. CONCLUSIONS: Despite the brevity of the treatment
      intervention, findings demonstrate that it resulted in substantial reductions in
      AS that were largely maintained 6 months posttreatment. Anxiety treatment and
      prevention implications are discussed.

PMID- 22468910
TI  - Design of a high-throughput flow perfusion bioreactor system for tissue
      engineering.
AB  - Flow perfusion culture is used in many areas of tissue engineering and offers
      several key advantages. However, one challenge to these cultures is the
      relatively low-throughput nature of perfusion bioreactors. Here, a flow perfusion
      bioreactor with increased throughput was designed and built for tissue
      engineering. This design uses an integrated medium reservoir and flow chamber in
      order to increase the throughput, limit the volume of medium required to operate
      the system, and simplify the assembly and operation.

PMID- 22468911
TI  - Statement of Retraction: Salama N, Kishimoto T, Kanayama HO, Kagawa S. "The
      mobile phone decreases fructose but not citrate in rabbit semen: a longitudinal
      study".

PMID- 22468912
TI  - Going further than Lipinski's rule in drug design.
AB  - INTRODUCTION: Lipinski's 1997 publication of the 'Rule of 5' (Ro5) was one of the
      most influential recent medicinal chemistry publications. In the almost 15 years
      since the publication of the original Ro5 paper, multiple groups have refined and
      expanded on the Ro5 and proposed additional heuristics to guide medicinal
      chemistry programs. While many variations on the Ro5 have been proposed, the
      majority of these remain close to the original guidelines proposed by Lipinski et
      al. AREAS COVERED: This review provides an overview of heuristic methods for the
      design of drug-like molecules. The article also provides the reader with
      suggestions on future directions for the field. EXPERT OPINION: While Lipinski's
      publication of the Ro5 and subsequent work by other authors has made medicinal
      chemists more aware of the relationships between physical properties and ADMET,
      it has hardly been a panacea. Pharmaceutical productivity continues to lag, and
      the industry is exploring new models to improve its output. If we are to
      progress, we need to move beyond simple models based on lipophilicity and gain a
      deeper understanding of molecular interactions.

PMID- 22468913
TI  - The impact of assay technology as applied to safety assessment in reducing
      compound attrition in drug discovery.
AB  - INTRODUCTION: Attrition in the drug industry due to safety findings remains high
      and requires a shift in the current safety testing paradigm. Many companies are
      now positioning safety assessment at each stage of the drug development process,
      including discovery, where an early perspective on potential safety issues is
      sought, often at chemical scaffold level, using a variety of emerging
      technologies. Given the lengthy development time frames of drugs in the
      pharmaceutical industry, the authors believe that the impact of new technologies
      on attrition is best measured as a function of the quality and timeliness of
      candidate compounds entering development. AREAS COVERED: The authors provide an
      overview of in silico and in vitro models, as well as more complex approaches
      such as 'omics,' and where they are best positioned within the drug discovery
      process. EXPERT OPINION: It is important to take away that not all technologies
      should be applied to all projects. Technologies vary widely in their validation
      state, throughput and cost. A thoughtful combination of validated and emerging
      technologies is crucial in identifying the most promising candidates to move to
      proof-of-concept testing in humans. In spite of the challenges inherent in
      applying new technologies to drug discovery, the successes and recognition that
      we cannot continue to rely on safety assessment practices used for decades have
      led to rather dramatic strategy shifts and fostered partnerships across
      government agencies and industry. We are optimistic that these efforts will
      ultimately benefit patients by delivering effective and safe medications in a
      timely fashion.

PMID- 22468914
TI  - Using label-free screening technology to improve efficiency in drug discovery.
AB  - INTRODUCTION: Screening assays have traditionally utilized reporter labels to
      quantify biological responses relevant to the disease state of interest. However,
      there are limitations associated with the use of labels that may be overcome with
      temporal measurements possible with label-free. AREAS COVERED: This review
      comprises general and system-specific information from literature searches using
      PubMed, published books and the authors' personal experience. This review
      highlights the label-free approaches in the context of various applications. The
      authors also note technical issues relevant to the development of label-free
      assays and their application to HTS. EXPERT OPINION: The limitations associated
      with the use of transfected cell lines and the use of label-based assays are
      gradually being realized. As such, greater emphasis is being placed on label-free
      biophysical techniques using native cell lines. The introduction of 96- and 384
      well plate label-free systems is helping to broker a wider acceptance of these
      approaches in high-throughput screening. However, potential users of the
      technologies remain skeptical, primarily because the physical basis of the
      signals generated, and their contextual relevance to cell biology and signal
      transduction, has not been fully elucidated. Until this is done, these new
      technology platforms are more likely to complement, rather than replace,
      traditional screening platforms.

PMID- 22468915
TI  - Molecular topology as a novel approach for drug discovery.
AB  - INTRODUCTION: Molecular topology (MT) has emerged in recent years as a powerful
      approach for the in silico generation of new drugs. One key part of MT is that,
      in the process of drug design/discovery, there is no need for an explicit
      knowledge of a drug's mechanism of action unlike other drug discovery methods.
      AREAS COVERED: In this review, the authors introduce the topic by explaining
      briefly the most common methodology used today in drug design/discovery and
      address the most important concepts of MT and the methodology followed (QSAR
      equations, LDA, etc.). Furthermore, the significant results achieved, from this
      approach, are outlined and discussed. EXPERT OPINION: The results outlined herein
      can be explained by considering that MT represents a new paradigm in the field of
      drug design. This means that it is not only an alternative method to the
      conventional methods, but it is also independent, that is, it represents a
      pathway to connect directly molecular structure with the experimental properties
      of the compounds (particularly drugs). Moreover, the process can be realized also
      in the reverse pathway, that is, designing new molecules from their topological
      pattern, what opens almost limitless expectations in new drugs development, given
      that the virtual universe of molecules is much greater than that of the existing
      ones.

PMID- 22468916
TI  - Models for narcolepsy with cataplexy drug discovery.
AB  - INTRODUCTION: Narcolepsy is a chronic sleep disorder, characterized by a
      disrupted nocturnal sleep, excessive daytime sleepiness (EDS) and symptoms of
      dissociated rapid eye movement (REM) sleep. These symptoms are often disabling,
      confining the patients to a life-long pharmacologic symptomatic treatment.
      Nowadays, it is well known that narcolepsy results from alterations in the genes
      involved in the physiology of the orexin ligand or its receptor. AREAS COVERED:
      This review recapitulates on the current approaches for treating narcolepsy with
      cataplexy and the use of narcolepsy models in order to address different aspects
      of the disease. EXPERT OPINION: Animal models are required for the study of human
      diseases when it is impractical or unethical to use humans; these models are
      useful for studying the underlying causes of a disease and are a common research
      tool for identifying potential drug targets. Current treatment for human
      narcolepsy is symptomatically based; interestingly, the existing approaches do
      not target the orexinergic circuit. The discovery of novel drug targets for
      treating narcolepsy remains the primary focus of study in sleep medicine
      research. New therapies will arise through the discovery of new animal models of
      narcolepsy, which will offer new insights into the understanding of its
      physiopathology.

PMID- 22468917
TI  - Evidence from basic research for opioid combinations.
AB  - INTRODUCTION: Single opioid analgesics are modestly effective in reducing pain
      but have a narrow therapeutic index and frequently produce intolerable side
      effects. Adjuvant analgesics are often used to improve the opioid therapeutic
      index. Basic science research has accumulated evidence that opioid combinations
      in animal models and in vitro have potential to improve the therapeutic index of
      opioids and/or prevent opioid tolerance. AREAS COVERED: Opioid receptor
      pharmacology is reviewed including receptor genetics and downstream signaling.
      Receptor functional selectivity and ligand biased responses are discussed in
      relationship to opioid pharmacodynamics, signal modulation and synergy. The
      accumulated bench research over the past decade, in particular, provides a
      rationale for considering clinical trials of opioid combinations. These
      combinations include both selective agonist-agonist or agonist-antagonist pairs
      which are reviewed. EXPERT OPINION: The use of opioid antagonists (naloxone and
      naltrexone), oxycodone, fentanyl and methadone with morphine improves analgesia
      in animal models and blunts physical dependence and conditioned place preference
      (a marker for psychological dependence). Sequential or simultaneous dosing
      schedules, dose levels or ratios need to be explored further. Pain phenotype may
      be an important factor predicting responses to combinations such that trial
      design will need to take this into account. Side effects will need to be
      monitored closely as little is known about the influence of opioid combinations
      on side effects.

PMID- 22468918
TI  - Same or not the same? Comparison of adipose tissue-derived versus bone marrow
      derived mesenchymal stem and stromal cells.
AB  - Mesenchymal stem/stromal cells (MSCs) comprise a heterogeneous population of
      cells with multilineage differentiation potential, the ability to modulate
      oxidative stress, and secrete various cytokines and growth factors that can have
      immunomodulatory, angiogenic, anti-inflammatory and anti-apoptotic effects.
      Recent data indicate that these paracrine factors may play a key role in MSC
      mediated effects in modulating various acute and chronic pathological conditions.
      MSCs are found in virtually all organs of the body. Bone marrow-derived MSCs (BM
      MSCs) were discovered first, and the bone marrow was considered the main source
      of MSCs for clinical application. Subsequently, MSCs have been isolated from
      various other sources with the adipose tissue, serving as one of the alternatives
      to bone marrow. Adipose tissue-derived MSCs (ASCs) can be more easily isolated;
      this approach is safer, and also, considerably larger amounts of ASCs can be
      obtained compared with the bone marrow. ASCs and BM-MSCs share many biological
      characteristics; however, there are some differences in their immunophenotype,
      differentiation potential, transcriptome, proteome, and immunomodulatory
      activity. Some of these differences may represent specific features of BM-MSCs
      and ASCs, while others are suggestive of the inherent heterogeneity of both BM
      MSC and ASC populations. Still other differences may simply be related to
      different isolation and culture protocols. Most importantly, despite the minor
      differences between these MSC populations, ASCs seem to be as effective as BM
      MSCs in clinical application, and, in some cases, may be better suited than BM
      MSCs. In this review, we will examine in detail the ontology, biology,
      preclinical, and clinical application of BM-MSCs versus ASCs.

PMID- 22468919
TI  - "SAFE" SINUS LIFT - USE OF ACRYLIC STONE TRIMMER TO AVOID SINUS LINING
      PERFORATION.
AB  - Abstract   Abstract Iatrogenic injury to the maxillary sinus membrane is a common
      complication during direct sinus lift procedures. The most common cause being the
      perforation of the Schneiderian membrane using a tungsten-carbide round bur no.6.
      We propose a safe technique by using an acrylic stone trimmer to create a window
      in the maxillary antrum thereby minimizing the risk of injury to the delicate
      sinus membrane.

PMID- 22468920
TI  - Free radical oxidation of cardiolipin: chemical mechanisms, detection and
      implication in apoptosis, mitochondrial dysfunction and human diseases.
AB  - Cardiolipin (CL) is a mitochondria-specific phospholipid and is critical for
      maintaining the integrity of mitochondrial membrane and mitochondrial function.
      CL also plays an active role in mitochondria-dependent apoptosis by interacting
      with cytochrome c (cyt c), tBid and other important Bcl-2 proteins. The unique
      structure of CL with four linoleic acid side chains in the same molecule and its
      cellular location make it extremely susceptible to free radical oxidation by
      reactive oxygen species including free radicals derived from peroxidase activity
      of cyt c/CL complex, singlet oxygen and hydroxyl radical. The free radical
      oxidation products of CL have been emerged as important mediators in apoptosis.
      In this review, we summarize the free radical chemical mechanisms that lead to CL
      oxidation, recent development in detection of oxidation products of CL by mass
      spectrometry and the implication of CL oxidation in mitochondria-mediated
      apoptosis, mitochondrial dysfunction and human diseases.

PMID- 22468921
TI  - Refractory anemia with ring sideroblasts associated with marked thrombocytosis
      harboring cytogenetic abnormality dup(2)(p15p22) treated with decitabine.

PMID- 22468922
TI  - Environmental tobacco smoke exposure during intrauterine period promotes
      granulosa cell apoptosis: a prospective, randomized study.
AB  - OBJECTIVE: To evaluate the intrauterine effect of cigarette smoke on cell death
      and DNA damage in follicular cells of fetal ovarian tissue. METHODS: A
      prospective, randomized study was conducted with 25 female wistar-albino rats.
      The rats were randomized to be exposed either to cigarette smoke or to room air,
      initiating from proestrous period and during pregnancy. Newborn female rats were
      categorized as Group 1 (n = 24) that had been exposed to cigarette smoke during
      intrauterine life and Group 2 (n = 7) that had been exposed to room air during
      intrauterine life. Bilateral ooferectomies were performed on the 2nd week of
      their life. TUNEL (in-situ Terminal Deoxynucleotidyl-Transferase Mediated dUTP
      Nick-End Labeling) immunofluorescent staining and immunohistochemical analyses
      with caspase-3 were used for detection of DNA damage and apoptosis. Primary
      outcomes were apoptotic index and immunohistochemical scores (HSCORE). Secondary
      outcomes were ovarian follicle counts and birth weights of newborn rats. RESULTS:
      There was a significant increase of HSCORE and apoptotic index in Group 1.
      Increased immunofluorescent staining; evaluating DNA damage, with TUNEL method
      was observed in granulosa cells in Group 1. CONCLUSIONS: Intrauterine exposure to
      cigarette smoke diminishes ovarian reserve of female offspring, raising the
      concern about the generational impact of maternal smoking on ovarian function in
      the human.

PMID- 22468923
TI  - Chemical recognition in cell-imprinted polymers.
AB  - A glass slide covered with bacteria is pressed into another glass slide coated
      with partially cured polydimethylsiloxane (PDMS). The PDMS is hardened and the
      cells are removed to create a textured surface whose indentations preferentially
      capture the same type of bacteria when a mixture of bacteria is flowed over it.
      Overcoating the cell-imprinted PDMS with methylsilane groups causes the resulting
      surface to lose much of its ability to preferentially capture the imprinted
      bacteria, although the shapes of the imprints, measured by atomic force field
      microscopy, are shown to be hardly affected. We interpret this behavior as strong
      evidence that chemical recognition plays a dominant role in cell sorting with
      cell-imprinted PDMS polymer films.

PMID- 22468924
TI  - Dual Bronsted acid/nucleophilic activation of carbonylimidazole derivatives.
AB  - Carbonylimidazole derivatives have been found to be highly active acylation
      reagents for esterification and amidation in the presence of pyridinium salts.
      These reactions are thought to involve both Bronsted acid and nucleophilic
      catalysis. This mode of activation has been applied to the synthesis of difficult
      to access oxazolidinones, as well as esters and amides. Finally, the use of
      pyridinium salts has been shown to accelerate the esterification of carboxylic
      acids with imidazole carbamates.

PMID- 22468925
TI  - Method development for metaproteomic analyses of marine biofilms.
AB  - The large-scale identification and quantitation of proteins via nanoliquid
      chromatography (LC)-tandem mass spectrometry (MS/MS) offers a unique opportunity
      to gain unprecedented insight into the microbial composition and biomolecular
      activity of true environmental samples. However, in order to realize this
      potential for marine biofilms, new methods of protein extraction must be
      developed as many compounds naturally present in biofilms are known to interfere
      with common proteomic manipulations and LC-MS/MS techniques. In this study, we
      used amino acid analyses (AAA) and LC-MS/MS to compare the efficacy of three
      sample preparation methods [6 M guanidine hydrochloride (GuHCl) protein
      extraction + in-solution digestion + 2D LC; sodium dodecyl sulfate (SDS) protein
      extraction + 1D gel LC; phenol protein extraction + 1D gel LC] for the
      metaproteomic analyses of an environmental marine biofilm. The AAA demonstrated
      that proteins constitute 1.24% of the biofilm wet weight and that the compared
      methods varied in their protein extraction efficiencies (0.85-15.15%). Subsequent
      LC-MS/MS analyses revealed that the GuHCl method resulted in the greatest number
      of proteins identified by one or more peptides whereas the phenol method provided
      the greatest sequence coverage of identified proteins. As expected, metagenomic
      sequencing of the same biofilm sample enabled the creation of a searchable
      database that increased the number of protein identifications by 48.7% (>=1
      peptide) or 54.7% (>=2 peptides) when compared to SwissProt database
      identifications. Taken together, our results provide methods and evidence-based
      recommendations to consider for qualitative or quantitative biofilm metaproteome
      experimental design.

PMID- 22468927
TI  - Population study on the predictors of sleeping difficulties in young Australian
      women.
AB  - Gender disparity in sleep difficulties in young adults may be driven by higher
      rates of affective disorders in women. This article investigated a range of
      factors as potential predictors of "difficulty sleeping" in 9,061 women aged 24
      to 30 years, using survey data. Regression analyses and odds ratios showed that
      depression and anxiety symptoms were indeed the greatest predictors of difficulty
      sleeping. However, 4 variables (binge-drinking, lower qualifications,
      dissatisfaction with excessive weight, and a history of abuse) also made
      significant contributions to sleep difficulty when a range of other variables
      (including depression and anxiety symptoms) were statistically controlled.
      Affective problems often predict sleep difficulties in young women, but other
      predictors are also significant and not necessarily intertwined with anxiety and
      depression.

PMID- 22468928
TI  - Television viewing, internet use, and self-reported bedtime and rise time in
      adults: implications for sleep hygiene recommendations from an exploratory cross
      sectional study.
AB  - This study examined whether the availability of the Internet and TV in the
      bedroom and overall Internet use and TV viewing were related to sleep variables
      in a sample of 711 residents of Flanders, Belgium. Although the relations were
      small, there was some evidence of time shifting: Internet access in the bedroom
      predicted later bedtime (beta = .12, p < .05) and later rise time (beta = .11, p
      < .05) on weekdays and later bedtime (beta = .10, p < .001) on weekends. Internet
      use volume predicted later bedtime (beta = .10, p < .001) and rise time (beta =
      .07, p < .05) on weekends, and TV viewing predicted later bedtime (beta = .10, p
      < .05) on weekends. However, neither the availability of the Internet or TV in
      the bedroom, nor the volume of Internet use or TV viewing, was a significant
      predictor of reduced sleep window or tiredness. Reducing media use might not be
      important for sleep hygiene advice to adults.

PMID- 22468929
TI  - Chronic insomnia and health care utilization in young adults.
AB  - Chronic insomnia is prevalent, contributes a significant economic burden, and
      people with insomnia have increased health care utilization (HCU). The purpose of
      this study was to investigate the relationship between chronic insomnia and HCU
      in a population with fewer medical/mental health problems, using current
      operational definitions of chronic insomnia and multiple measures of HCU.
      Participants with chronic insomnia had greater HCU than normal sleepers.
      Participants with chronic insomnia plus a comorbid condition had greater HCU than
      normal sleepers with a medical/mental health problem and participants with only
      chronic insomnia. The relationship between chronic insomnia and HCU was moderated
      by comorbid medical/mental health problems. Early identification and intervention
      of chronic insomnia may help reduce HCU and costs associated with chronic
      insomnia.

PMID- 22468930
TI  - Physical activity in sleep apnea and obesity-personal incentives, challenges, and
      facilitators for success.
AB  - The purpose of this study was to explore aspects of engagement in physical
      activity in persons with obstructive sleep apnea and overweight. Seven women and
      8 men were interviewed, and transcribed data were analyzed according to
      qualitative content analysis. Two themes evolved reflecting influences on
      engagement in physical activity: (a) incentives strong enough and (b)
      facilitators for success and challenges to overcome. Strong incentives to change
      seem crucial for engagement in physical activity. The identified challenges and
      facilitators concerned a spectrum of emotional and contextual aspects, as well as
      diseases and physical symptoms. Exploring the patient's expectations on physical
      activity behavior change and the perceived facilitators and barriers for
      engagement may be helpful when tailoring behavioral support strategies.

PMID- 22468931
TI  - A pilot study of shoulder placement for actigraphy in children.
AB  - Children with neurodevelopmental disorders may have difficulty tolerating devices
      that monitor sleep, presenting challenges in measuring sleep disturbances in this
      population. Although wrist actigraphy has advantages over polysomnography, some
      children remain unable to tolerate wrist placement. This study piloted an
      alternative site for actigraphy in 8 children with autism, ages 6-10 years.
      Results are presented from the 2 locations (custom pocket shoulder location and
      wrist location) using Bland-Altman limits of agreement and other statistical
      measures to compare sleep onset latency, total sleep time, sleep efficiency, and
      wake after sleep onset. The use of an alternative actigraphy site for children
      with autism, who have difficulty tolerating actigraphy placement, appears
      promising and worthy of further study.

PMID- 22468932
TI  - Measurement of adhesion work of electrospun polymer membrane by shaft-loaded
      blister test.
AB  - The work of adhesion at the interface of electrospun membrane and rigid substrate
      is measured by a shaft-loaded blister test (SLBT). Poly(vinylidene fluoride)
      (PVDF) were electrospun with an average fiber diameter of 333 +/- 59 nm.
      Commercial cardboard with inorganic coating was used to provide a model substrate
      for adhesion tests. In SLBT, the elastic response PVDF was analyzed and its
      adhesion energy measured. The average value of the adhesion work is 206 +/- 26
      mJ/m(2). Elastic modulus of electrospun membrane obtained by SLBT is found to be
      23.42 +/- 2.69 MPa, which is consistent with the value obtained from standard
      tensile tests. The results show SLBT presented a viable methodology for
      evaluating the adhesion energy of electrospun polymer fabrics. 

PMID- 22468933
TI  - Clinical outcomes of primary angioplasty in ST elevation myocardial infarction
      patients with antecedent hypertension during hospital stay and follow-up.
AB  - Hypertension is a known risk factor for coronary artery disease. However, the
      number of studies focusing on the events following ST elevation myocardial
      infarction (STEMI) in patients with an antecedent hypertension is limited. Our
      aim is to evaluate the clinical outcomes of primary angioplasty in STEMI patients
      with antecedent hypertension during hospital stay and follow-up. A total of 373
      patients (177 of whom had antecedent hypertension) who were treated by primary
      angioplasty because of STEMI were included in this study. All parameters were
      compared between the groups with and without hypertension. Hypertensive patients
      who received primary angioplasty were older (59.9 +/- 12.6 vs. 52 +/- 12.3, P <
      .001) and had higher rates of in-hospital mortality and major adverse cardiac
      events than patients without hypertension. Among STEMI patients, only history of
      hypertension for more than 10 years was a predictor of in-hospital mortality
      (odds ratio: 4.374, 95% CI 1.017-18.822, P = .04). Patients with an antecedent
      hypertension have higher initial risk profiles and show more negative outcomes
      during a 6-month follow-up period.

PMID- 22468934
TI  - Development of calculation and analysis methods for the dynamic first
      hyperpolarizability based on the ab initio molecular orbital-quantum master
      equation method.
AB  - We develop novel calculation and analysis methods for the dynamic first
      hyperpolarizabilities beta [the second-order nonlinear optical (NLO) properties
      at the molecular level] in the second-harmonic generation based on the quantum
      master equation method combined with the ab initio molecular orbital (MO)
      configuration interaction method. As examples, we have evaluated off-resonant
      dynamic beta values of donor (NH(2))- and/or acceptor (NO(2))-substituted
      benzenes using these methods, which are shown to reproduce those by the
      conventional summation-over-states method well. The spatial contributions of
      electrons to the dynamic beta of these systems are also analyzed using the
      dynamic beta density and its partition into the MO contributions. The present
      results demonstrate the advantage of these methods in unraveling the mechanism of
      dynamic NLO properties and in building the structure-dynamic NLO property
      relationships of real molecules.

PMID- 22468935
TI  - Self nano-emulsifying simvastatin based tablets: design and in vitro/in vivo
      evaluation.
AB  - The aim of this work is to improve the oral bioavailability of poorly water
      soluble drug, simvastatin (SV) through combining the advantages of self
      nanoemulsifying systems (SNEs) and tablets. Ternary phase diagram was constructed
      using Labrafil, Tween 80 and Transcutol, in order to evaluate self
      nanoemulsification domain. The particle size distribution and zeta potential of
      the prepared systems were evaluated using Malvern Zetasizer. Liquisolid powders
      were prepared using Aeroperl((r)) as a coating material and Avicel((r)) or Starch
      1500 as carrier materials, the powder flow properties were then evaluated.
      Compressed SV SNE based tablets were evaluated regarding their physical
      characteristics, in-vitro release properties as well as in-vivo pharmacokinetic
      evaluation in six healthy human volunteers using a validated LC/MS/MS method. The
      in-vitro release results revealed that the developed SNE based tablets improved
      the release of SV significantly, compared to commercially available SV tablets
      (Zocor((r))). The optimal SV SNE tablet formulation was S3St10 (10% Labrafil, 60%
      Tween 80, and 30% Transcutol). The in-vivo evaluation of S3St10 revealed that
      rapid and enhanced absorption of SV could be obtained from the SNE based tablet,
      with a 1.5 fold increase in bioavailability than that obtained after
      administration of Zocor((r)). Hence such an approach could be promising in
      improving the bioavailability of SV. 

PMID- 22468936
TI  - Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and
      characterization of the potent, selective, and orally efficacious agonist 5-(4
      acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl]
      amide (SEN15924, WAY-361789).
AB  - Alpha-7 nicotinic acetylcholine receptors (alpha7 nAChR) are implicated in the
      modulation of many cognitive functions such as attention, working memory, and
      episodic memory. For this reason, alpha7 nAChR agonists represent promising
      therapeutic candidates for the treatment of cognitive impairment associated with
      Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around
      our previously reported chemical series, permitted the discovery of a novel class
      of alpha7 nAChR agonists with improved selectivity, in particular against the
      alpha3 receptor subtype and better ADME profile. The exploration of this series
      led to the identification of 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4
      methoxyphenyl)-1H-pyrazol-3-yl] amide (25, SEN15924, WAY-361789), a novel, full
      agonist of the alpha7 nAChR that was evaluated in vitro and in vivo. Compound 25
      proved to be potent and selective, and it demonstrated a fair pharmacokinetic
      profile accompanied by efficacy in rodent behavioral cognition models (novel
      object recognition and auditory sensory gating).

PMID- 22468937
TI  - End state copying by humans (Homo sapiens): implications for a comparative
      perspective on cumulative culture.
AB  - It has been proposed that the uniqueness of human cumulative culture may be
      attributable to humans' greater orientation toward copying the process of
      behavior (imitation), as compared with the products (emulation), resulting in
      particularly high fidelity transmission. Following from previous work indicating
      that adult human participants can exhibit cumulative learning on the basis of
      product copying alone, we now investigate whether such learning involves high
      fidelity transmission. Eighty adult human (Homo sapiens) participants were
      presented with a task previously shown to elicit cumulative learning under
      experimental conditions, which involved building a tower from spaghetti and
      modeling clay. Each participant was shown two completed towers, ostensibly built
      by previous participants, but actually built to prespecified designs by the
      experimenter. This end state information was provided either in the form of
      photographs, or the presence of actual towers. High fidelity matching to these
      end states was apparent in both demonstration conditions, even for a design that
      was demonstrably suboptimal with regard to the goal of the task (maximizing tower
      height). We conclude that, although high fidelity transmission is likely to be
      implicated in cumulative culture, action copying is not always necessary for this
      to occur. Furthermore, since chimpanzees apparently copy behavioral processes and
      well as products, and also transmit behavior with high fidelity, the stark
      absence of unequivocal examples of cumulative culture in nonhumans may be
      attributable to factors other than imitative ability.

PMID- 22468938
TI  - Characteristics of serial order learning in common marmosets (Callithrix
      jacchus).
AB  - We investigated the characteristics of serial order learning in common marmosets
      (Callithrix jacchus). Five marmosets were trained in a sequential responding task
      in which they were required to touch four graphic patterns in a given order (A->B
      >C->D) to obtain a reward. All five marmosets learned the task with over 65%
      accuracy. Shuffling the positions of B, C, and D immediately after the marmoset
      had correctly identified and selected the first stimulus (A) either decreased
      accuracy or lengthened response latency for the second stimulus (B). These
      results suggest that the marmosets planned the response to the second stimulus
      before they touched the first stimulus. In addition, when we presented a pair of
      stimuli (AB, AC, AD, BC, BD, and CD pairs), the marmosets responded to the
      stimuli in the pair in the appropriate order, according to the learned order (A
      >B->C->D). The analyses of first and second response latencies clearly
      demonstrated both the first-item and missing-item effects in task performance.
      Our data provide direct evidence that marmosets can learn the relative order of
      the four stimuli in a sequential responding task.

PMID- 22468939
TI  - Effects of overtraining on extinction in newts (Cynops pyrrhogaster).
AB  - The overtraining extinction effect (OEE), a phenomenon in which extended training
      facilitates extinction, has been found in mammals and reptiles. However, fish
      have never shown OEE. No study has yet investigated OEE in newts, a
      representative amphibian species. We tested whether newts, Cynops pyrrhogaster,
      show OEE in a straight-array task. All animals received five trials per day and
      were given a piece of dried worm during reinforced trials. They showed
      significant acquisition and extinction effects in reinforced and nonreinforced
      trials. However, we found no difference in extinction performance between a group
      with 25-trial acquisition and one with 75-trial acquisition, suggesting that OEE
      was not found in newts. OEE has generally been explained in terms of frustration
      related mechanisms. Our results suggest that emotional reactions to nonreward,
      such as frustration, may not influence behavior in amphibians.

PMID- 22468940
TI  - Follicular thyroid carcinoma arising after hematopoietic stem cell
      transplantation in a child with pleuropulmonary blastoma.
AB  - BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic
      neoplasm that is associated with other dysplastic or neoplastic conditions. The
      prognosis, especially of type II (cystic and solid) and type III (solid) PPB, is
      poor. High-dose chemotherapy (HDC) and hematopoietic stem cell transplantation
      (HSCT) have been attempted to improve survival rates. We report the development
      of follicular thyroid carcinoma in a girl who was treated at a young age for PPB.
      SUMMARY: A 23-month-old girl was evaluated for a clinical diagnosis of pneumonia
      and was found to have a mass in the left lung that grew rapidly. It was removed
      and diagnosed as a PPB. At the age of two, she was referred to our hospital for
      further treatment. She received adjuvant chemotherapy for 6 months but developed
      a recurred mass in her back at 4.3 years of age. After removal of the mass, she
      was given a salvage chemotherapy followed by HDC and HSCT but not radiation
      treatment between 4.4 and 4.9 years of age. At the age of seven, after 2 years
      without treatment, she presented with multiple thyroid nodules in both lobes that
      steadily grew over the next 2 years. At the age of nine, she underwent total
      thyroidectomy, which revealed an invasive follicular carcinoma. She remained
      without clinical evidence of thyroid cancer for one year since the surgery.
      Radiation therapy was not administered because of the concerns of causing another
      malignancy. A literature search combined with the present case indicated that, of
      the five living patients who had been treated with HDC and HSCT, three developed
      a follicular thyroid carcinoma. CONCLUSIONS: The high prevalence (3/5, 60%) of
      follicular thyroid carcinoma in patients with PPB who were treated with HDC and
      HSCT is striking. This suggests that, in patients with PPB, either HDC or HSCT
      contributes to the development of thyroid cancer. Clinicians should be advised of
      the high risk of thyroid carcinoma occurrence when HDC and HSCT are being
      contemplated in children with PPB.

PMID- 22468941
TI  - Pregnant French women living in the Lyon area are iodine deficient and have
      elevated serum thyroglobulin concentrations.
AB  - BACKGROUND: Iodine deficiency (ID) remains common in Europe, and may be
      especially detrimental during pregnancy. The aim of our study was to assess
      iodine status and thyroid function in healthy pregnant women in the Lyon
      metropolitan area. METHODS: In a cross-sectional study, healthy pregnant women
      (n=228) with no history of thyroid disease were consecutively recruited from an
      obstetric clinic during all trimesters. Thyrotropin (TSH), free thyroxine (FT4),
      anti-thyroid peroxidase (anti-TPO) antibodies, thyroglobulin (Tg), and urinary
      iodine concentration (UIC) (n=100) were measured. Thyroid functions were compared
      with those in a control group of nonpregnant adults. RESULTS: The median (range)
      UIC was 81 (8-832) MUg/L, and 77% of pregnant women had a UIC <150 MUg/L,
      indicating inadequate iodine intake. Overall, 11% of women had abnormal TSH or
      anti-TPO. The median FT4 (pmol/L) was 14.9, 12.6, and 11.5 in the first, second,
      and third trimesters, respectively. The median Tg in pregnant women was 16.2
      MUg/L, did not differ across trimesters, and was significantly higher than in the
      control group of nonpregnant adults (11.7 MUg/L) (p=0.02). Controlling for
      maternal age and week of gestation, UIC was not a significant predictor of any of
      the thyroid function tests. CONCLUSIONS: Pregnant women in the Lyon area are
      iodine deficient and have increased serum Tg concentrations compared with
      nonpregnant controls, likely due to physiological thyroid hyperstimulation during
      gestation exacerbated by ID.

PMID- 22468942
TI  - The importance of imaging procedures in evaluating painful neck masses: two
      patients with a painful internal jugular vein thrombosis.

PMID- 22468943
TI  - Pituitary antibodies in women with Hashimoto's thyroiditis: prevalence in
      diagnostic and prediagnostic sera.
AB  - BACKGROUND: Pituitary antibodies have been reported with greater frequency in
      patients with Hashimoto's thyroiditis than in healthy controls, although there is
      significant variability in the strength of the association and the methodologies
      used. METHODS: We designed a nested case-control study to characterize the
      prevalence of pituitary antibodies at the time of the clinical diagnosis of
      Hashimoto's thyroiditis, as well as at 2, 5, and 7 years before diagnosis. Active
      component female service member cases (n=87) and matched female controls (n=107)
      were selected using the Defense Medical Surveillance System database (DMSSD)
      between January 1998 and December 2007. Pituitary antibodies were measured by
      immunofluorescence using human pituitary glands collected at autopsy as the
      substrate. RESULTS: At diagnosis, pituitary antibodies were present in 9% of
      cases with Hashimoto's (8 of 87) and 3% of controls (3 of 107). When the data
      were analyzed using a conditional logistic regression model, which takes into
      account the matching on age and work status, pituitary antibodies increased the
      odds of having Hashimoto's thyroiditis by sevenfold (95% confidence interval from
      1.3 to 40.1, p=0.028), after adjusting for components of the DMSSD-category
      termed race and for thyroperoxidase antibodies. Before diagnosis, pituitary
      antibodies were positive in 3 of the 11 subjects (2 cases and 1 control) at the 
      2-year time point, and negative in all 11 subjects at the -5- and -7-year time
      points. CONCLUSIONS: In summary, using a nested case-control design, we confirm
      that pituitary antibodies are more common in Hashimoto's thyroiditis and suggest
      that they appear late during its natural history.

PMID- 22468944
TI  - Molecular magnetism of M6 hexagon ring in D(3d) symmetric [(MCl)6(XW9O33)2](12-)
      (M = Cu(II) and Mn(II), X = Sb(III) and As(III)).
AB  - Ferromagnetic [n-BuNH(3)](12)[(CuCl)(6)(SbW(9)O(33))(2)].6H(2)O (1) and
      antiferromagnetic [n-BuNH(3)](12)[(MnCl)(6)(AsW(9)O(33))(2)].6H(2)O (4) have been
      synthesized and structurally and magnetically characterized. Two complexes are
      structural analogues of [n-BuNH(3)](12)[(CuCl)(6)(AsW(9)O(33))(2)].6H(2)O (2) and
      [n-BuNH(3)](12)[(MnCl)(6)(SbW(9)O(33))(2)].6H(2)O (3) with their ferromagnetic
      interactions, first reported by us in 2006. (1) When variable temperature (T)
      direct current (dc) magnetic susceptibility (chi(M)) data are analyzed with the
      isotropic exchange Hamiltonian for the magnetic exchange interactions, chi(M)T vs
      T curves fitted by a full matrix diagonalization (for 1) and by the Kambe vector
      coupling method/Van Vleck's approximation (for 4) yield J = +29.5 and -0.09 cm(
      1) and g = 2.3 and 1.9, respectively. These J values were significantly
      distinguished from +61.0 and +0.14 cm(-1) for 2 and 3, respectively. The
      magnetization under the pulsed field (up to 10(3) T/s) at 0.5 K exhibits
      hysteresis loops in the adiabatic process, and the differential magnetization
      (dM/dB) plots against the pulsed field display peaks characteristic of resonant
      quantum tunneling of magnetization (QTM) at Zeeman crossed fields, indicating
      single-molecule magnets for 1-3. High-frequency ESR (HFESR) spectroscopy on
      polycrystalline samples provides g(?) = 2.30, g(?) = 2.19, and D = -0.147 cm(-1)
      for 1 (S = 3 ground state), g(?) = 2.29, g(?) = 2.20, and D = -0.145 cm(-1) for 2
      (S = 3), and g(?) = 2.03 and D = -0.007 cm(-1) for 3 (S = 15). An attempt to
      rationalize the magnetostructural correlation among 1-4, the structurally and
      magnetically modified D(3d)-symmetric M (=Cu(II) and Mn(II))(6) hexagons
      sandwiched by two diamagnetic alpha-B-[XW(9)O(33)](9-) (X = Sb(III) and As(III))
      ligands through M-(MU(3)-O)-W linkages, is made. The strongest ferromagnetic
      coupling for the Cu(6) hexagon of 2, the structure of which approximately
      provides the Cu(6)(MU(3)-O)(12) cylindrical geometry, is demonstrated by the
      polarization mechanism based on the point-dipole approximation, which provides a
      decrease of the ferromagnetic interaction due to the out-of-cylinder deviation of
      the Cu atoms for 1. The different nature of the magnetic exchange interaction in
      3 and 4 is understood by the combined effect of the out-of plane deviation (the
      largest for 4) of the Mn atoms from the Mn(MU(3)-O)(2)Mn least-squares plane and
      the antiferromagnetic contribution arising from the large Mn-O-Mn bond angle. The
      primary contribution to D is discussed in terms of the magnetic dipole-dipole
      interaction between the electrons located on the magnetic sites in the M(6)
      hexagon.

PMID- 22468945
TI  - Concord grape juice supplementation and neurocognitive function in human aging.
AB  - Polyphenol compounds found in berry fruits, in particular flavonoids, have been
      associated with health benefits including improvement in cognition and neuronal
      function with aging. Concord grape juice contains polyphenols, including
      anthocyanins and flavanols, and previous research has shown improvement in a
      number of human health conditions with grape juice supplementation. In the
      current study, older adult subjects with mild cognitive impairment consumed
      Concord grape juice or placebo for 16 weeks and were administered assessments of
      memory function and brain activation pre- and postintervention. Participants who
      consumed grape juice showed reduced semantic interference on memory tasks.
      Relatively greater activation in anterior and posterior regions of the right
      hemisphere was also observed with functional magnetic resonance imaging in the
      grape juice treated subjects. These findings provide further evidence that
      Concord grape juice can enhance neurocognitive function in older adults with mild
      memory decline. 

PMID- 22468946
TI  - The level of alexithymia in alcohol-dependent patients does not influence
      outcomes after inpatient treatment.
AB  - BACKGROUND: The inability of individuals with Alcohol Use Disorders (AUD) to
      recognize and describe their feelings and cravings may be due to alexithymia.
      Previous researches have shown evidence for a negative influence of alexithymia
      on treatment outcomes in patients with AUD. Therefore, it was hypothesized that
      high alexithymic patients with AUD would benefit less from cognitive behavioral
      therapy (CBT) compared with low alexithymic patients. METHODS: One hundred
      alcohol-dependent inpatients (DSM IV) were assessed with the Mini International
      Neuropsychiatric Interview for psychiatric disorders, the Toronto Alexithymia
      Scale (TAS-20), and the European Addiction Severity Index (EuropASI). Baseline
      alexithymia, as a categorical and continuous variable, was used to compare or
      relate baseline demographic and addiction characteristics, time in treatment,
      abstinence, and differences in addiction severity at 1-year follow-up. Analyses
      were performed using chi(2) test, analysis of variance or Kruskal-Wallis, paired
      t-tests or Wilcoxon's signed rank tests, multivariate logistic, and linear
      regression models, as appropriate. RESULTS: The prevalence of high alexithymia
      (TAS-20 > 61) was 45%. The total TAS-20 score correlated negatively with years of
      education (r = -.21; p = .04) and positively with the psychiatry domain of the
      EuropASI (r = .23; p = .04). Alexithymia showed no relation to abstinence, time
      in treatment, or change in severity of alcohol-related problems on the EuropASI.
      CONCLUSION: High alexithymic patients with AUD do benefit equally from inpatient
      CBT-like treatment as low alexithymic patients with AUD. SCIENTIFIC SIGNIFICANCE:
      Multimethod alexithymia assessments with an observer scale have been advised to
      judge the relationship with resulting outcome in CBT.

PMID- 22468947
TI  - Sex ratio and women's career choice: does a scarcity of men lead women to choose
      briefcase over baby?
AB  - Although the ratio of males to females in a population is known to influence
      behavior in nonhuman animals, little is known about how sex ratio influences
      human behavior. We propose that sex ratio affects women's family planning and
      career choices. Using both historical data and experiments, we examined how sex
      ratio influences women's career aspirations. Findings showed that a scarcity of
      men led women to seek high-paying careers and to delay starting a family. This
      effect was driven by how sex ratio altered the mating market, not just the job
      market. Sex ratios involving a scarcity of men led women to seek lucrative
      careers because of the difficulty women have in finding an investing, long-term
      mate under such circumstances. Accordingly, this low-male sex ratio produced the
      strongest desire for lucrative careers in women who are least able to secure a
      mate. These findings demonstrate that sex ratio has far-reaching effects in
      humans, including whether women choose briefcase over baby.

PMID- 22468948
TI  - Effect of lifestyle modification and metformin therapy on emerging cardiovascular
      risk factors in overweight Indian women with polycystic ovary syndrome.
AB  - INTRODUCTION: Polycystic ovarian syndrome (PCOS) is common among women of
      reproductive age. Although traditional cardiac risk factors are known to be
      altered and improved with short-term metformin therapy, not much is known about
      novel cardiac risk factors. OBJECTIVE: The aim of this study was to evaluate the
      effects of lifestyle modification and short-term metformin therapy on the fasting
      serum lipids, homeostasis model assessment of insulin resistance (HOMA-IR), serum
      high-sensitivity C-reactive protein (hsCRP), and serum homocysteine. METHODS:
      Native overweight [body mass index (BMI) >23 kg/m(2)] Indian women diagnosed with
      PCOS were evaluated and subjected to an oral glucose tolerance test and
      determination of insulin, homocysteine, hsCRP, and fasting lipids levels. They
      were started on maximally tolerated doses of metformin along with lifestyle
      modification. Following 3 months of therapy, they were resampled. RESULTS: Out of
      36 consecutive patients included, 25 women completed 3 months of metformin
      treatment and were eligible for repeat evaluation. The age of study group was
      22.2 +/- 5 years. Twenty-two (61%) women were obese (BMI >25 kg/m(2)).
      Improvement was seen in body weight, BMI, serum total cholesterol, triglycerides,
      high-density lipoprotein cholesterol (HDL-C), hsCRP, and serum testosterone on
      metformin therapy. However, no improvement was seen in serum fasting insulin,
      HOMA-IR, or homocysteine. CONCLUSION: Serum hsCRP improved with lifestyle
      modification and metformin therapy for 3 months in overweight subjects from India
      with PCOS, along with serum total cholesterol, triglycerides, and HDL-C. However,
      markers of insulin resistance and serum homocysteine did not improve.

PMID- 22468950
TI  - Cyclotides as a basis for drug design.
AB  - INTRODUCTION: Cyclotides are plant-made defence proteins with a head-to-tail
      cyclic backbone combined with a conserved, six cystine knot. They have a range of
      biological activities, including uterotonic and anti-HIV activity, which have
      attracted attention to their potential pharmaceutical applications. Furthermore,
      their unique structures and high stability make them appealing as peptide-based
      templates for drug design applications. Methods have been developed for their
      production, including solid phase peptide synthesis as well as recombinant
      methods. AREAS COVERED: This article reviews the recent literature associated
      with therapeutic applications of naturally occurring and synthetically modified
      cyclotides. It includes applications of cyclotides and cyclotide-like molecules
      as peptide-based drug leads and diagnostic agents. EXPERT OPINION: The ultra
      stable cyclotides are promising templates for drug development applications and
      are currently being assessed for the potential breadth of their applications. For
      synthetic versions of cyclotides to enter human clinical trials further studies
      to examine their biopharmaceutical properties and toxicities are required.
      However, several promising proof-of-concept studies have established that
      pharmaceutically relevant bioactive peptide sequences can be grafted into
      cyclotide frameworks and thereby stabilised, while maintaining biological
      activity. These studies include examples directed at cancer, cardiovascular
      disease and infectious diseases. Solid phase peptide synthesis has been the
      preferred approach for making pharmaceutically modified cyclotides so far, but
      promising progress is being made in biological approaches to cyclotide
      production.

PMID- 22468949
TI  - Thyroid hormone promotes neuronal differentiation of embryonic neural stem cells
      by inhibiting STAT3 signaling through TRalpha1.
AB  - A deficiency of maternal thyroid hormones (THs) during pregnancy may have severe
      impacts on fetal brain development. However, the cellular targets of THs and
      their underlying mechanisms are still unclear. In this study, we found that
      maternal hypothyroidism during pregnancy in mice inhibited neurogenesis in the
      embryonic telencephalon and caused learning and memory impairment in the
      offspring. To explore the underlying mechanisms, we treated cultured mouse
      embryonic neural stem cells (eNSCs) with a physiological level of 3, 5, 3'
      triiodo-L-thyronine (T3). We found that T3 promoted the neuronal differentiation
      of eNSCs, while inhibiting astrocytic differentiation. In addition, the
      proliferation and maintenance of eNSCs were inhibited by T3. Furthermore, the TH
      receptor alpha 1 (TRalpha1) was detected in the eNSCs both in vivo and in vitro.
      Silencing TRalpha1 protein expression with specific siRNA eliminated the effects
      of T3 on eNSCs. We also found that T3 decreased STAT3 phosphorylation and STAT3
      DNA binding activity through TRalpha1. The over expression of STAT3 attenuated
      the promotive effects of T3 on neuronal differentiation of eNSCs. Taken together,
      these results suggest that T3 promotes the neuronal differentiation of eNSCs by
      inhibiting STAT3 signaling activity through TRalpha1 and contributes to early
      neurogenesis in the embryonic telencephalon. Our studies reveal the physiological
      effects of TH in regulating eNSCs differentiation and suggest that eNSCs are one
      of the major cellular targets in the central nervous system by which TH
      influences early brain development. These findings also provide new insights into
      the mechanisms of neurological deficits caused by TH deficiency during
      embryogenesis.

PMID- 22468951
TI  - Simple and efficient model systems of screening anti-Toxoplasma drugs in vitro.
AB  - INTRODUCTION: A lot of in vitro technologies have been developed to screen drugs
      for toxoplasmosis, which is caused by Toxoplasma gondii and is one of the most
      serious infectious diseases in the world. However, developed screening methods
      still have limitation such as inaccuracy, labor-intensive and time-consuming
      procedure. Therefore, the development of simpler, more efficient and accurate
      high-throughput screening assay is needed. AREAS COVERED: The present review
      gives the overview of in vitro screening technologies described in literatures so
      far including morphological assay, incorporation of [(3)H]uracil assay, enzyme
      linked immunosorbent assay (ELISA), colorimetric microtiter assay (beta
      galactosidase assay), flow cytometric quantification assay, yellow fluorescent
      protein assay and cell viability assay. The authors discuss how these methods are
      efficient and/or limited for screening anti-T. gondii drugs. The authors further
      suggest brand-new technologies which are faster, simpler, more effective and
      available for high-throughput screening. EXPERT OPINION: Options for clinical
      treatment of toxoplasmosis are currently very limited. Thus, more accurate in
      vitro screening methods must be established to identify the most effective anti
      T. gondii drugs from random screening of compounds. At the same time, based on
      genome information, combination of an appropriate screening technology,
      combinatorial chemistry and computational biology may increase the efficiency of
      target-based drug discovery against T. gondii.

PMID- 22468952
TI  - Preclinical mouse models and methods for the discovery of the causes and
      treatments of atherosclerosis.
AB  - INTRODUCTION: Atherosclerosis is the leading cause of death in the Western world.
      Despite huge advances in understanding its pathophysiological mechanisms, current
      treatment is mostly based on 'traditional' risk factors. The introduction of
      statins more than 20 years ago reduced morbidity and mortality of atherosclerosis
      by 30%, leaving a residual cardiovascular risk. Therefore, efforts continue
      toward the development of novel therapies that can be added to established
      treatments. Besides targeting dyslipidemia, recent focus has been put on
      preventing or resolving inflammatory processes involved in atherosclerosis. AREAS
      COVERED: The article discusses therapeutic and diagnostic targets in
      atherosclerosis and how they can be discovered and studied in preclinical animal
      models. The roles of immune cells, specifically macrophages and monocytes, in
      plaque inflammation are discussed. The article also describes current preclinical
      models of atherosclerosis, specifically the mouse, study designs (for progression
      and regression studies), basic and advanced methods of analysis of
      atherosclerotic lesions, and discusses the challenges of translating the findings
      to humans. EXPERT OPINION: Advances in genomics, proteomics, lipidomics and the
      development of high-throughput screening techniques help to improve our
      understanding of atherosclerosis disease mechanisms immensely and facilitate the
      discovery of new diagnostic and therapeutic targets. Preclinical studies in
      animals are still indispensable to uncover pathways involved in atherosclerotic
      disease and to evaluate novel drug targets. The translation of these targets,
      however, from animal studies to humans remains challenging. There is a strong
      need for novel biomarkers that can be used to prove the concept of a new target
      in humans.

PMID- 22468953
TI  - Aging biology: a new frontier for drug discovery.
AB  - INTRODUCTION: The prevalence of age-related pathologies, such as cardiovascular
      disease, neurodegenerative disease and diabetes type II, has increased
      dramatically with the rising average age of populations. Antiaging molecules and
      appropriate animal models need to be developed to prevent and or delay
      alterations that occur during aging and are manifested as age-associated
      illnesses. AREAS COVERED: This review covers the main experimental models used in
      aging research, from invertebrates up to nonhuman primates. The authors discuss
      studies of the biochemical pathways involved in dietary restriction, which has
      been associated with life span extension. The authors also describe the
      implications of sirtuin 1, insulin growth factor, mTOR (the mammalian target of
      rapamycin) and AMPK activation, which are well-characterized antiaging pathways.
      All these pathways are highly conserved from invertebrates to nonhuman primates.
      Although some invertebrate models are used to study the antiaging properties of
      drugs, mice models and nonhuman primates are more suitable, as the study of
      changes in memory loss is critical. The review highlights the conservation of the
      aging pathways between species. EXPERT OPINION: Further studies on aging should
      focus on two ways: i) improving animal models, for example, the genetically
      heterogeneous mice and ii) drug research. It is almost impossible to evaluate
      clinically the efficacy of antiaging drugs. Moreover, caloric restriction
      currently constitutes the most effective antiaging pathway. Thus, the strategy is
      to study drugs for aging-associated diseases, such as diabetes, that also have
      antiaging effects.

PMID- 22468955
TI  - Gene expression profiling and therapeutic interventions in neurodegenerative
      diseases: a comprehensive study on potentiality and limits.
AB  - INTRODUCTION: Neurodegenerative diseases are incurable debilitating disorders of
      the nervous system that affect approximately 30 million people worldwide. Despite
      profuse efforts attempting to define the molecular mechanisms underlying
      neurodegeneration, many aspects of these pathologies remain elusive. The novelty
      of their mechanisms represents a challenge to biology, to their related
      biomarkers identification and drug discovery. Because of their multifactorial
      aspects and complexity, gene expression analysis platforms have been extensively
      used to investigate altered pathways during degeneration and to identify
      potential biomarkers and drug targets. AREAS COVERED: This work offers an
      overview of the gene expression profiling studies carried out on Alzheimer's
      disease, Huntington's disease, Parkinson's disease and prion disease specimens.
      Therapeutic approaches are also discussed. EXPERT OPINION: Although many
      therapeutic approaches have been tested, some of them acting on several altered
      cellular pathways, no effective cures for these neurodegenerative diseases have
      been identified. Microarray technology must be associated with functional
      proteomics and physiology in an effort to identify specific and selective
      biomarkers and druggable targets, thus allowing the successful discovery of
      disease-modifying therapeutic treatments.

PMID- 22468954
TI  - Third-generation sequencing techniques and applications to drug discovery.
AB  - INTRODUCTION: There is an immediate need for functional and molecular studies to
      decipher differences between disease and 'normal' settings to identify large
      quantities of validated targets with the highest therapeutic utilities.
      Furthermore, drug mechanism of action and biomarkers to predict drug efficacy and
      safety need to be identified for effective design of clinical trials, decreasing
      attrition rates, regulatory agency approval process and drug repositioning. By
      expanding the power of genetics and pharmacogenetics studies, next-generation
      nucleic acid sequencing technologies have started to play an important role in
      all stages of drug discovery. AREAS COVERED: This article reviews the first- and
      second-generation sequencing technologies (SGSTs) and challenges they pose to
      biomedicine. The article then focuses on the emerging third-generation sequencing
      technologies (TGSTs), their technological foundations and potential contributions
      to drug discovery. EXPERT OPINION: Despite the scientific and commercial success
      of SGSTs, the goal of rapid, comprehensive and unbiased sequencing of nucleic
      acids has not been achieved. TGSTs promise to increase sequencing throughput and
      read lengths, decrease costs, run times and error rates, eliminate biases
      inherent in SGSTs and offer capabilities beyond nucleic acid sequencing. Such
      changes will have positive impact on all sequencing applications to drug
      discovery.

PMID- 22468956
TI  - Recent advances in the drug discovery of metabotropic glutamate receptor 4
      (mGluR4) activators for the treatment of CNS and non-CNS disorders.
AB  - INTRODUCTION: The metabotropic glutamate receptor type 4 (mGluR4) plays a pivotal
      role in a plethora of therapeutic areas, as recently demonstrated in preclinical
      validation studies with several chemical classes of compounds in rodent models of
      central nervous system (CNS) and peripheral disorders. Activation of mGluR4 with
      orthosteric agonists, allosteric agonists or pure positive allosteric modulators
      (PAM) has been postulated to be of broad therapeutic use. AREAS COVERED: The
      authors address past and current drug discovery efforts, insights and
      achievements in the field toward the identification of therapeutically promising
      and emerging class of mGluR4 activators, over the 2005 - 2011 period. Chemical
      structures, properties and in vivo pharmacological results discussed in the
      present review were retrieved from public literature including PubMed searches,
      Thomson Pharma and SciFinder databases searches, conferences, proceedings and
      posters. EXPERT OPINION: Developing a subtype-selective, orally bioavailable
      brain penetrant mGluR4 orthosteric agonist remains challenging. Lack of subtype
      selectivity and low brain penetration has been a common limitation of the first
      generation of mGluR4 agonist and potentiators. However, significant progress has
      recently been made with the identification of several double- to single-digit
      nanomolar mGluR4 PAM having reasonable pharmacokinetic properties, oral
      bioavailability and brain penetration. The use of such compounds in research has
      led to advancement in understanding the central role of mGluR4 in multiple
      neurodegenerative and neuroinflammatory disorders, such as Parkinson's disease
      and multiple sclerosis. Our understanding of the potential application of mGluR4
      as therapeutic target is expected to grow as these compounds advance into
      preclinical and clinical development.

PMID- 22468957
TI  - "Side change" of a fetal ovarian cyst: key to diagnosis.

PMID- 22468958
TI  - A new heligmonellid (Nematoda: Heligmonellidae) from Oecomys mamorae (Rodentia:
      Sigmodontinae) in the Pantanal and new data on the synlophe of Guerrerostrongylus
      zetta from the Atlantic Forest, Brazil.
AB  - A new species of Heligmonellidae nematode, Guerrerostrongylus gomesae n. sp., is
      described from specimens collected from the small intestine of the rodent Oecomys
      mamorae Thomas, 1906 in the Brazilian Pantanal. It differs from the 2 other
      species of the genus by the number of ridges in the synlophe 35-46 and 40-48 at
      the midbody in the male and female, respectively, by rays 8 arising at midlength
      of the dorsal trunk, ending near the margin of the caudal bursa, and the dorsal
      ray divided at the second-third part into 2 branches, each branch divided into 2
      subequal subbranches. In addition, specimens of Guerrerostrongylus zetta
      Travassos, 1937 collected in Oligoryzomys nigripes Olfers, 1818 contain synlophe
      with 36-42 cuticular ridges in males and 38-42 in females at the midbody. By the
      characteristics of the synlophe and caudal bursa, Gerrerostrongylus gomesae n.
      sp. is considered a new species. We suggest that the number of cuticular ridges
      for this genus broadens the range of the cuticular ridges to at least 35 at
      midbody.

PMID- 22468959
TI  - Fatty liver induced by free radicals and lipid peroxidation.
AB  - An excessive accumulation of fat in the liver leads to chronic liver injury such
      as non-alcoholic fatty liver disease (NAFLD), which is an important medical
      problem affecting many populations worldwide. Oxidative stress has been
      implicated in the pathogenesis of NAFLD, but the exact nature of active species
      and the underlying mechanisms have not been elucidated. It was previously found
      that the administration of free radical-generating azo compound to mice induced
      accumulation of fat droplet in the liver. The present study was performed aiming
      at elucidating the changes of lipid classes and fatty acid composition and also
      measuring the levels of lipid peroxidation products in the liver induced by azo
      compound administration to mouse. The effects of azo compound on the liver were
      compared with those induced by high fat diet, a well-established cause of NAFLD.
      Azo compounds given to mice either by intraperitoneal administration or by
      dissolving to drinking water induced triacylglycerol (TG) increase and
      concomitant phospholipid decrease in the liver, whose pattern was quite similar
      to that induced by high fat diet. Lipid peroxidation products such as
      hydroxyoctadecadienoic acid and hydroxyeicosatetraenoic acid were increased in
      the liver in association with the increase in TG. These results show that free
      radicals as well as high fat diet induce fatty liver by similar mechanisms, in
      which lipid peroxidation may be involved.

PMID- 22468960
TI  - Magnetically mediated vortexlike assembly of gold nanoshells.
AB  - Gold nanoshells currently attract increasing research interests due to the
      important role in many subjects. For practical applications, random arrangement
      of the nanoparticles is often unfavored so that the assembly of gold nanoshells
      is becoming a central issue. We here proposed to utilize time-variant magnetic
      field to direct the assembly of gold nanoshells. It was discovered that the
      alternating magnetic field can mediate the vortex-like assembly of gold
      nanoshells. The mechanism was explored and thought to be relative with the
      electric field of induction which caused the thermal gradient on the substrate
      and the electric force. The vortexlike structure as well as the assembly
      mechanism will play an important role in research and application of gold
      nanomaterials. 

PMID- 22468961
TI  - Cytokine-conditioned dendritic cells induce humoral tolerance to protein therapy
      in mice.
AB  - A major obstacle in the genetic therapy of inherited metabolic disease is host
      immune responses to the therapeutic protein. This is best exemplified by
      inhibitor formation in the protein therapy for hemophilia A. An approach to
      overcoming this is induction of immunological tolerance to the therapeutic
      protein. Tolerogenic dendritic cells (DCtols) have been reported to induce
      tolerance. In addition, cytokines such as interleukin (IL)-10 and transforming
      growth factor (TGF)-beta(1) are known to induce tolerance. To model protein
      therapy, we used ovalbumin (OVA) as antigen in BALB/c mice and their transgenic
      derivative, DO11.10 mice. In this study we show that adoptive transfer of antigen
      pulsed dendritic cells (DCs) treated with a combination of IL-10 and TGF-beta(1)
      can suppress the antibody response in mice. Adoptive transfer of cytokine
      conditioned DCs in preimmunized mice results in reduction of antibody response in
      the mice. Furthermore, the effect is antigen specific, as the recipient mice were
      able to mount a potent antibody response to the control antigen. Last, we show
      that TGF-beta(1) and IL-10-conditioned DCs are able to inhibit anti-FVIII
      antibody responses in FVIII knockout (KO) mice. Analysis of the contribution of
      IL-10 and TGF-beta(1) to the DCtol phenotype shows that IL-10 treatment of DCs is
      sufficient for inducing OVA-specific tolerance in BALB/c mice, but we observed a
      requirement for treatment with both human TGF-beta(1) and human IL-10 to
      significantly inhibit anti-FVIII antibody responses in FVIII KO mice. This paper
      demonstrates that autologous cell therapy for antigen-targeted immune suppression
      may be developed to facilitate long-term therapy.

PMID- 22468962
TI  - A single step approach to piperidines via Ni-catalyzed beta-carbon elimination.
AB  - An easy and expeditious route to substituted piperidines is described. A Ni
      phosphine complex was used as catalyst for [4 + 2] cycloaddition of 3-azetidinone
      and alkynes. The reaction has broad substrate scope and affords piperidines in
      excellent yields and excellent regioselectivity. In the reaction of an
      enantiopure azetidinone, complete retention of stereochemistry was observed.

PMID- 22468963
TI  - Baseline training in cognitive and psychodynamic psychotherapy during a
      psychologist training program. Exploring client outcomes in therapies of one or
      two semesters.
AB  - This effectiveness study explored the outcomes of 187 clients seen by 187
      students undergoing baseline training in psychotherapy. Clients reduced their
      symptoms (SCL-90) and increased their positive self-image (SASB introject) during
      the therapy. Multiple regression analyses showed no differences between the
      cognitive and the psychodynamic training approaches and no differences between
      one and two semesters duration of the therapies. However, 2-3% of variance in end
      states was accounted for by the interaction between the variables, indicating a
      moderating effect of duration in the two approaches. Outcomes for clients in the
      cognitive training approach were significantly better with two semesters than
      with one semester, while there was no such difference in the psychodynamic
      approach. Consequences for baseline training are discussed.

PMID- 22468964
TI  - Comment on "Enantiomer resolution by pressure increase: inferences from
      experimental and topological results for the binary enantiomer system (R)- and
      (S)-mandelic acid".

PMID- 22468965
TI  - Highly effective adsorption of heavy metal ions from aqueous solutions by
      macroporous xylan-rich hemicelluloses-based hydrogel.
AB  - Xylan-rich hemicelluloses-based hydrogel was developed as a novel porous
      bioadsorbent by graft co-polymerization of acrylic acid (AA) and xylan-rich
      hemicelluloses for adsorption of heavy metal ions (Pd(2+), Cd(2+), and Zn(2+))
      from aqueous solutions. The chemical structure, the interaction between the
      hydrogel and metal ions, and the porous structure of xylan-rich hemicelluloses-g
      AA hydrogel were revealed by Fourier transform infrared spectroscopy and scanning
      electron microscopy. The effects of AA and cross-linker dosage, pH value,
      contacting time, and initial concentration of metal ion on the adsorption
      capacity were studied. The adsorption equilibrium time was about 60 min from the
      adsorption kinetics study. The maximum adsorption capacities of Pd(2+), Cd(2+),
      and Zn(2+) were 859, 495, and 274 mg/g, respectively. Furthermore, xylan-rich
      hemicelluloses-g-AA hydrogel also exhibited highly efficient regeneration and
      metal ion recovery efficiency and can be reused without noticeable loss of
      adsorption capacity for Pd(2+), Cd(2+), and Zn(2+) after quite a number of
      repeated adsorption/desorption cycles.

PMID- 22468966
TI  - On the utility of isotopic fine structure mass spectrometry in protein
      identification.
AB  - Modern mass spectrometry (MS)-based protein identification and characterization
      relies upon accurate mass measurements of the (13)C isotopic distributions of the
      enzymatically produced peptides. Interestingly, obtaining peptide elemental
      composition information from its isotopic fine structure mass spectrum to
      increase the confidence in peptide and protein identification has not yet been
      developed into a bottom-up proteomics-grade analytical approach. Here, we discuss
      the possible utility and limitations of the isotopic fine structure MS for
      peptide and protein identification. First, we in silico identify the peptides
      from the E. coli tryptic digest and show the increased confidence in peptide
      identification by consideration of the isotopic fine structures of these peptides
      as a function of mass and abundance accuracies. In the following, we demonstrate
      that the state-of-the-art high magnetic field Fourier transform ion cyclotron
      resonance (FT-ICR) MS allows a routine acquisition of the isotopic fine structure
      information of a number of isobaric peptide pairs, including a pair of peptides
      originating from E. coli. Finally, we address the practical limitation of the
      isotopic fine structure MS implementation in the time-constraint experiments by
      applying an advanced signal processing technique, filter diagonalization method,
      to the experimental transients to overcome the resolution barrier set by the
      typically applied Fourier transformation. We thus demonstrate that the isotopic
      fine structures of peptides may indeed improve the peptide and possibly protein
      identification, can be produced in a routine experiment by the state-of-the-art
      high resolution mass spectrometers, and can be potentially obtained on a
      chromatographic time-scale of a typical bottom-up proteomics experiment. The
      latter one requires at least an order of magnitude increase in sensitivity of ion
      detection, which presumably can be realized using high-field Orbitrap FTMS and/or
      future generation of ultrahigh magnetic field FT-ICR MS equipped with harmonized
      ICR cells.

PMID- 22468967
TI  - Reactive polymer multilayers fabricated by covalent layer-by-layer assembly: 1,4
      conjugate addition-based approaches to the design of functional biointerfaces.
AB  - We report on conjugate addition-based approaches to the covalent layer-by-layer
      assembly of thin films and the post-fabrication functionalization of
      biointerfaces. Our approach is based on a recently reported approach to the
      "reactive" assembly of covalently cross-linked polymer multilayers driven by the
      1,4-conjugate addition of amine functionality in poly(ethyleneimine) (PEI) to the
      acrylate groups in a small-molecule pentacrylate species (5-Ac). This process
      results in films containing degradable beta-amino ester cross-links and residual
      acrylate and amine functionality that can be used as reactive handles for the
      subsequent immobilization of new functionality. Layer-by-layer growth of films
      fabricated on silicon substrates occurred in a supra-linear manner to yield films
      ~ 750 nm thick after the deposition of 80 PEI/5-Ac layers. Characterization by
      atomic force microscopy (AFM) suggested a mechanism of growth that involves the
      reactive deposition of nanometer-scale aggregates of PEI and 5-Ac during
      assembly. Infrared (IR) spectroscopy studies revealed covalent assembly to occur
      by 1,4-conjugate addition without formation of amide functionality. Additional
      experiments demonstrated that acrylate-containing films could be
      postfunctionalized via conjugate addition reactions with small-molecule amines
      that influence important biointerfacial properties, including water contact
      angles and the ability of film-coated surfaces to prevent or promote the
      attachment of cells in vitro. For example, whereas conjugation of the hydrophobic
      molecule decylamine resulted in films that supported cell adhesion and growth,
      films treated with the carbohydrate-based motif D-glucamine resisted cell
      attachment and growth almost completely for up to 7 days in serum-containing
      media. We demonstrate that this conjugate addition-based approach also provides a
      means of immobilizing functionality through labile ester linkages that can be
      used to promote the long-term, surface-mediated release of conjugated species and
      promote gradual changes in interfacial properties upon incubation in
      physiological media (e.g., over a period of at least 1 month). These covalently
      cross-linked films are relatively stable in biological media for prolonged
      periods, but they begin to physically disintegrate after ~ 30 days, suggesting
      opportunities to use this covalent layer-by-layer approach to design functional
      biointerfaces that ultimately erode or degrade to facilitate elimination.

PMID- 22468968
TI  - Hypertensive retinopathy: incidence, risk factors, and comorbidities.
AB  - We aimed to determine the prevalence and risk factors of retinopathy in
      hypertensive outpatients. Demographic data, accompanying diseases, anthropometric
      measurements, and blood and urine biochemistry of 655 hypertensive patients were
      evaluated. Hypertensive retinopathy rate was 66.3% (grade 1, 33.6%; grade 2,
      32.7%). Age, duration of hypertension, and systolic blood pressure levels were
      significant risk factors for retinopathy (P = .048, P = .035, and P = .012,
      respectively). Any correlations between retinopathy and gender, body mass index,
      biochemistry, and associated diseases were not found. This study shows that the
      degree and duration of hypertension increases the incidence of retinopathy. Low
      grade retinopathy seems not to be associated with other cardiovascular risks.

PMID- 22468969
TI  - Reaction of phenyl radical with propylene as a possible source of indene and
      other polycyclic aromatic hydrocarbons: an ab initio/RRKM-ME study.
AB  - Ab initio G3(MP2,CC)//B3LYP/6-311G** calculations have been performed to
      investigate the potential energy surface (PES) and mechanism of the reaction of
      phenyl radical with propylene followed by kinetic RRKM-ME calculations of rate
      constants and product branching ratios at various temperatures and pressures. The
      reaction can proceed either by direct hydrogen abstraction producing benzene and
      three C(3)H(5) radicals [1-propenyl (CH(3)CHCH), 2-propenyl (CH(3)CCH(2)), and
      allyl (CH(2)CHCH(2))] or by addition of phenyl to the CH or CH(2) units of
      propylene followed by rearrangements on the C(9)H(11) PES producing nine
      different products after H or CH(3) losses. The H abstraction channels are found
      to be kinetically preferable at temperatures relevant to combustion and to
      contribute 55-75% to the total product yield in the 1000-2000 K temperature
      range, with the allyl radical being the major product (~45%). The relative
      contributions of phenyl addition channels are calculated to be ~35% at 1000 K,
      decreasing to ~15% at 2000 K, with styrene + CH(3) and 3-phenylpropene + H being
      the major products. Collisional stabilization of C(6)H(5) + C(3)H(6) addition
      complexes is computed to be significant only at temperatures up to 1000-1200 K,
      depending on the pressure, and maximizes at low temperatures of 300-700 K
      reaching up to 90% of the total product yield. At T > 1200 K collisional
      stabilization becomes negligible, whereas the dissociation products, styrene plus
      methyl and 3-phenylpropene + H, account for up to 45% of the total product yield.
      The production of bicyclic aromatic species including indane C(9)H(10) is found
      to be negligible at all studied conditions indicating that the phenyl addition to
      propylene cannot be a source of polycyclic aromatic hydrocarbons (PAH) on the
      C(9)H(11) PES. Alternatively, the formation of a PAH molecule, indene C(9)H(8),
      can be accomplished through secondary reactions after activation of a major
      product of the C(6)H(5) + C(3)H(6) addition reaction, 3-phenylpropene, by direct
      hydrogen abstraction by small radicals, such as H, OH, CH(3), etc. It is shown
      that at typical combustion temperatures 77-90% of C(9)H(9) radicals formed by H
      abstraction from 3-phenylpropene undergo a closure of a cyclopentene ring via low
      barriers and then lose a hydrogen atom producing indene. This results in 7.0
      14.5% yield of indene relative to the initial C(6)H(5) + C(3)H(6) reactants
      within the 1000-2000 K temperature range.

PMID- 22468970
TI  - Development of a novel class of glucose transporter inhibitors.
AB  - On the basis of our finding that the antitumor effect of 5-{4-[(1
      methylcyclohexyl)methoxy]benzyl}thiazolidine-2,4-dione, a thiazolidinedione
      peroxisome proliferator-activated receptor (PPAR)gamma agonist, was, in part,
      attributable to its ability to block glucose uptake independently of PPARgamma,
      we used its PPARgamma-inactive analogue to develop a novel class of glucose
      transporter (GLUT) inhibitors. This lead optimization led to compound 30 {5-(4
      hydroxy-3-trifluoromethylbenzylidene)-3-[4,4,4-trifluoro-2-methyl-2-(2,2,2
      trifluoroethyl)butyl]thiazolidine-2,4-dione} as the optimal agent, which
      exhibited high antitumor potency through the suppression of glucose uptake
      (IC(50), 2.5 MUM), while not cytotoxic to prostate and mammary epithelial cells.
      This glucose uptake inhibition was associated with the inhibition of GLUT1
      (IC(50), 2 MUM). Moreover, the mechanism of antitumor action of compound 30 was
      validated by its effect on a series of energy restriction-associated cellular
      responses. Homology modeling analysis suggests that the inhibitory effect of
      compound 30 on glucose entry was attributable to its ability to bind to the GLUT1
      channel at a site distinct from that of glucose.

PMID- 22468971
TI  - HIV treatment optimism and sexual risk behaviors among HIV positive African
      American men who have sex with men.
AB  - The association between HIV treatment optimism--beliefs about susceptibility to
      transmit HIV, motivation to use condoms, and severity of HIV--and sexual risk
      behavior was examined among HIV-positive African American men who have sex with
      men (MSM). Participants were 174 men recruited in four major metropolitan areas
      of the United States to participate in a weekend HIV risk reduction intervention.
      Baseline results revealed that beliefs in less susceptibility to transmit HIV and
      less motivation to use condoms were significantly associated with more
      unprotected anal intercourse among serodiscordant casual partners. Less
      motivation to use condoms also predicted more unprotected insertive and receptive
      anal sex and was more important than susceptibility beliefs in predicting these
      behaviors. Suggestions are offered of ways to better inform HIV-positive African
      American MSM about their misperceptions about HIV treatment and how their level
      of optimism about HIV treatment may diminish or encourage condom use.

PMID- 22468972
TI  - Attitudes about and HIV risk related to the "most common place" MSM meet their
      sex partners: comparing men from bathhouses, bars/clubs, and Craigslist.org.
AB  - This study examined attitudes toward the most common place where men who have sex
      with men (MSM) met their recent male sex partners. In 2009-2010, MSM were
      surveyed in bars/clubs, bathhouses, and on Craigslist.org . We found strong but
      differential overlap between venue of recruitment and participants' most common
      place: 81% of men from Craigslist indicated their most common place was the
      Internet, 65% of men from bathhouses indicated their most common place was
      bathhouses, and 47% of men from bars/clubs indicated their most common place was
      bars/clubs. In general, interest in seeing more information on drugs/alcohol and
      HIV and interacting with a health outreach worker in participants' most common
      place ranged from "agree" to "strongly agree." However, men whose most common
      place was bars/clubs rated these items lowest on average. Rates of unprotected
      anal intercourse (UAI) were high (43%), thus targeted efforts in bars/clubs,
      bathhouses, and on the Internet may be ideal venues for reaching high-risk MSM.
      Although most common place was unrelated to UAI, it was related to factors that
      contextualize men's encounters (e.g., attitudes toward HIV status disclosure, and
      perceptions about barebacking, anonymous sex, and alcohol use). Outreach
      providers should consider these contextualizing aspects as they continue to
      retool their efforts.

PMID- 22468973
TI  - Real men are safe-culturally adapted: utilizing the Delphi process to revise real
      men are safe for an ethnically diverse group of men in substance abuse treatment.
AB  - Real Men Are Safe (REMAS) was effective at reducing the number of unprotected
      sexual occasions for men in substance abuse treatment compared to an HIV
      education control intervention. Utilizing a modified Delphi process, modules from
      REMAS were compared to similar-content modules from other CDC-approved,
      culturally tailored HIV prevention interventions. Utilizing ratings and
      recommendations obtained from an independent expert panel, REMAS was subsequently
      revised to be more culturally adapted for an ethnically diverse group of men.
      Ratings suggested REMAS was culturally fair, but that in certain areas the
      culturally tailored interventions were more in tune with African American and
      Hispanic men. Revisions to REMAS include an added focus on how culture, social
      norms, and upbringing affect a man's sexual behavior and relationships.

PMID- 22468974
TI  - Smoking, HIV status, and HIV risk behaviors in a respondent-driven sample of
      injection drug users in Baltimore, Maryland: The BeSure Study.
AB  - Tobacco use is the largest preventable cause of death in the United States.
      Associations between cigarette smoking and HIV risk behaviors were examined among
      669 injection drug users (IDU) in the 2006 wave of the National HIV Behavioral
      Surveillance System in Baltimore, Maryland, using respondent-driven sampling. The
      adjusted prevalence of smoking among IDU was 92.1%, with 32.7% smoking < 1 pack
      of cigarettes per day (light smoking) and 59.3% smoking >= 1 packs per day (heavy
      smoking). Self-reported HIV prevalence decreased as smoking frequency increased
      (p = 0.001). In multivariate analysis, heavy smokers were more likely to report
      painkiller use and binge drinking and less likely to report anal sex or health
      care use in the past year than light smokers. Results suggest that health care
      use mediates the relationship between heavy smoking and self-reported HIV.
      Integrating smoking cessation with HIV prevention services could address unmet
      health needs in IDU.

PMID- 22468975
TI  - Factors Related to HIV testing among an African American church-affiliated
      population.
AB  - HIV continues to disproportionately impact communities of color, and more calls
      are being extended to African American churches to assist in HIV education and
      screening efforts. However, no studies have reported on the HIV testing practices
      of African American church-affiliated persons. This study examines demographic,
      social, and behavioral factors associated with ever receiving an HIV test and
      last 12-month HIV testing. Findings indicated not having insurance and condom use
      were predictors of ever receiving an HIV test. Predictors of HIV testing in the
      last 12 months included marital status (i.e., single, divorced, separated, or
      widowed) and intentions to get tested for HIV in the near future. These
      predictors should be considered when designing HIV education and screening
      interventions for African American church settings.

PMID- 22468977
TI  - Helping patients talk about HIV: inclusion of messages on disclosure in
      prevention with positives interventions in clinical settings.
AB  - Disclosure of HIV serostatus by HIV-infected individuals is considered a
      prevention strategy, under the assumption that disclosure will prompt risk
      reduction practices among sex partners. We examined patients' self-reports
      regarding disclosure messages they found relevant as part of prevention with
      positives (PwP) interventions in clinical settings. We conducted 52 in-depth
      interviews with patients participating in 13 PwP interventions. We found that the
      opportunity to reflect about living with HIV, explore fears of stigma and
      rejection, develop communication skills and strategies to disclose, and explore a
      sense of responsibility influenced patients' intention to disclose and their
      disclosure practices. PwP interventions need to include a combination of messages
      about disclosure strategies, stigma, and communication, as well as helping
      patients frame disclosure as a process that includes situations and interactions
      to consider post-disclosure. PwP disclosure counseling can help influence a shift
      in patients' risk towards safer sex practices.

PMID- 22468976
TI  - Condom use with various types of sex partners by money boys in China.
AB  - Money boys (MBs) who typically sell sex to males have not yet been extensively
      studied in China. In this 2009 study, 28 venue-based MBs were interviewed. We
      analyzed their condom use behaviors with various partners, including male and
      female clients, male and female casual partners, other MBs and female sex
      workers, and boyfriends and girlfriends. All participants were aware of the need
      for using condoms; however, usage with different partner types varied. The longer
      a relationship with a partner, the less frequent was condom use. A major reason
      for not using condoms was that they or their partners did not like the loss of
      sensation due to condom use. Other factors included sexual orientation, age,
      duration in commercial sex, concerns about HIV/AIDS, attractiveness of partners,
      and support of "mommies" (brothel supervisors). Both individual- and venue-level
      interventions are needed to promote condom use, and mommies need to be included
      in intervention strategies.

PMID- 22468978
TI  - Solubilization of entecavir by povidone to overcome content uniformity challenges
      for low-dose tablet formulations.
AB  - Development of 0.1, 0.5, and 1.0 mg entecavir tablet formulations for the
      treatment of hepatitis B virus was challenging for content uniformity. Entecavir
      with pKa of 2.8 and 9.8 does not have sufficient solubility in acidic or alkaline
      medium or in common pharmaceutical solvents such as ethanol to dissolve the drug
      in granulating fluid to prepare the homogeneous granulation. Povidone (PVP), a
      commonly used binder, was found to increase entecavir solubility depending on the
      PVP concentration and temperature of the solution. At 15% w/w PVP concentration,
      entecavir solubility increased from 2 mg/mL to about 8 mg/mL at room temperature.
      When the PVP solution was heated to 50 degrees C or 70 degrees C, the solubility
      was increased to about 23 or 33 mg/mL, respectively. Based on Raman spectra of
      entecavir in PVP solution, the increase in entecavir solubility in the presence
      of PVP may not be due to any molecular interactions between them. Solubilization
      of entecavir in PVP and eventual granulation did not change the polymorphic form
      of the drug based on the powder X-ray and differential scanning calorimetric
      (DSC), and thermo-gravimetric analysis (TGA) of neat entecavir re-crystallized
      from the PVP solution. The enhancement in the solubility of entecavir by PVP was
      sufficient to keep the amount of solution, which was used for granulation, to be
      about 20% w/w of the batch size like the traditional aqueous granulation. The
      granulation manufactured using this approach provided better tablet content
      uniformity than one using micronized entecavir. 

PMID- 22468979
TI  - Long term neuropsychological outcome and management of 'decompensated'
      longstanding overt ventriculomegaly in adults.
AB  - OBJECTIVE: We aimed to study a group of patients presenting with symptomatic
      longstanding overt ventriculomegaly in adults (LOVA) requiring treatment
      (endoscopic third ventriculostomy), and to study their long term
      neuropsychological status and functionality. METHODS: Twenty patients were
      treated with endoscopic third ventriculostomy on presentation and were studied
      with neuropsychological assessments including the repeatable battery for the
      assessment of neuropsychological status and the hospital anxiety and depression
      scores. Pre- and post-operative MRI studies were used to assess the patency of
      the endoscopic third ventriculostomy (ETV) along with clinical outcome scores.
      RESULTS: A variety of presenting symptoms were experienced including headache
      (90%), worsening imbalance, attacks of loss of consciousness and cognitive
      decline. Mean age of patients was 52 years (range, 17-78) with mean head
      circumference of 60.9 cm. ETV was successful in controlling symptoms in 89% of
      patients with three patients requiring shunts (gravitational valves). There were
      no subdurals after surgery. All patients did universally badly in all aspects of
      the neuropsychological studies without showing any undue anxiety or depression.
      CONCLUSION: LOVA patients can decompensate at any time in their adult life with
      acute symptoms, which are generally well controlled with ETV and with few
      complications. Sadly, the long-term effects of carrying 'asymptomatic' or
      compensated hydrocephalus since childhood are of a significant cognitive cost to
      these patients.

PMID- 22468980
TI  - Carbon-carbon reductive elimination from homoleptic uranium(IV) alkyls induced by
      redox-active ligands.
AB  - The synthesis, characterization, and reactivity of the homoleptic uranium(IV)
      alkyls U(CH(2)C(6)H(5))(4) (1-Ph), U(CH(2)-p-CH(3)C(6)H(4))(4) (1-p-Me), and
      U(CH(2)-m-(CH(3))(2)C(6)H(3))(4) (1-m-Me(2)) are reported. The addition of 4
      equiv of K(CH(2)Ar) (Ar = Ph, p-CH(3)C(6)H(4), m-(CH(3))(2)C(6)H(3)) to UCl(4) at
      -108  degrees C produces 1-Ph in good yields and 1-p-Me and 1-m-Me(2) in moderate
      yields. Further characterization of 1-Ph by X-ray crystallography confirmed
      eta(4)-coordination of each benzyl ligand to the uranium center. Magnetic studies
      produced an effective magnetic moment of 2.60 MU(B) at 23  degrees C, which is
      consistent with a tetravalent uranium 5f(2) electronic configuration. Addition of
      1 equiv of the redox-active alpha-diimine (Mes)DAB(Me) ((Mes)DAB(Me) =
      [ArN?C(Me)C(Me)?NAr]; Ar = 2,4,6-trimethylphenyl (Mes)) to 1-Ph results in
      reductive elimination of 1 equiv of bibenzyl (PhCH(2)CH(2)Ph), affording
      ((Mes)DAB(Me))U(CH(2)C(6)H(5))(2) (2-Ph). Treating an equimolar mixture of 1-Ph
      and 1-Ph-d(28) with (Mes)DAB(Me) forms the products from monomolecular reductive
      elimination, 2-Ph, 2-Ph-d(14), bibenzyl, and bibenzyl-d(14). This is confirmed by
      (1)H NMR spectroscopy and GC/MS analysis of both organometallic and organic
      products. Addition of 1 equiv of 1,2-bis(dimethylphosphino)ethane (dmpe) to 1-Ph
      results in formation of the previously synthesized (dmpe)U(CH(2)C(6)H(5))(4) (3
      Ph), indicating the redox-innocent chelating phosphine stabilizes the uranium
      center in 3-Ph and prevents reductive elimination of bibenzyl. Full
      characterization for 3-Ph, including X-ray crystallography, is reported.

PMID- 22468981
TI  - Circulating cytokine signatures in healthy medical students exposed to academic
      examination stress.
AB  - Stress-induced production of proinflammatory cytokines in the brain and periphery
      is associated with mental distress. In this study, we measured changes in levels
      of salivary cortisol and 50 circulating immune mediators in 28 4th-grade medical
      students (19 males and 9 females) 7 weeks before, 1 day before, immediately
      after, and 1 week after an authorized nationwide examination for promotion.
      Repeated measures ANOVA with multiple testing correction and post hoc tests
      revealed that the examination significantly increased levels of proinflammatory
      cytokines (granulocyte colony-stimulating factor, interferon-gamma, interleukin
      (IL)-1beta, and tumor necrosis factor-alpha), Th2 cytokines (IL-4, IL-5, and IL
      13), and beta-nerve growth factor in association with significant decreases in
      salivary cortisol levels and anxiety after the examination. These mediators may
      have a negative impact on the mental state of healthy young adults exposed to
      naturalistic stressors.

PMID- 22468982
TI  - Effects of endosulfan intoxication on pituitary functions.
AB  - CONTEXT: We investigated the effects of endosulfan intoxication on pituitary
      functions in three patients. METHODS: This is an observational case series
      including three patients with endosulfan intoxication. Patients were evaluated 3
      months after the acute event. RESULTS: Based on the baseline hormonal values and
      dynamic endocrine tests, one patient had hypothalamo-pituitary-adrenal axis
      impairment and was diagnosed as ACTH deficiency (peak cortisol level was found
      13.12 MUg/dl after low dose ACTH stimulation test), and another one had GH-IGF-I
      axis impairment and was diagnosed as GH deficiency (peak GH level was found 1.06
      MUg/L after glucagon stimulation test). CONCLUSIONS: Endosulfan intoxication
      might cause pituitary hormone deficiencies after the acute phase. Therefore,
      patients with endosulfan toxicity should be followed for possible pituitary gland
      dysfunction.

PMID- 22468983
TI  - Telemedicine for the reduction of myocardial infarction mortality: a systematic
      review and a meta-analysis of published studies.
AB  - INTRODUCTION: Advances in electronics and communications have changed modern
      medicine: telemedicine allows patient assessment and monitoring to facilitate
      healthcare at a distance. The aim of this study was to perform a systematic
      review and meta-analysis to assess how telemedicine systems, including early
      telemetry of electrocardiograms, can improve health outcomes in patients with
      coronary artery disease and, in particular, acute myocardial infarction (AMI).
      METHODS: Studies dealing with telemedicine applications in managing AMI that were
      conducted before January 22, 2010, published in English or Italian, were
      identified in PubMed and ISI Web of Knowledge searches. The meta-analysis was
      performed to assess the efficacy of telemedicine versus standard measures in
      reducing mortality. Relative risk (RR) with 95% confidence interval was used to
      report results and the I(2) test to evaluate heterogeneity. RESULTS: Five of the
      39 articles retrieved were selected; all studies demonstrated the efficacy of
      telemedicine applications. Only three studies were judged to be comparable and
      suitable for combining data. This meta-analysis showed that the RR for in
      hospital mortality from AMI was 0.65 (95% confidence interval, 0.42-0.99) for the
      telemedicine group, without heterogeneity. CONCLUSIONS: Telemedicine may improve
      health outcomes of patients with AMI. However, heterogeneity in study design and
      end points of most studies limited the number of articles that could be subjected
      to our meta-analysis.

PMID- 22468984
TI  - Group diabetes education administered through telemedicine: tools used and
      lessons learned.
AB  - OBJECTIVE: To describe the use of telemedicine for teaching group diabetes
      education classes to individuals with diabetes mellitus in a rural medically
      underserved area. SUBJECTS AND METHODS: Adults with diabetes from a rural area
      served by Oswego Hospital in upstate New York were asked to participate in this
      study. Volunteers received diabetes education through real-time teleconferencing
      (n=27) by joining age- and sex-matched patients from the Joslin Diabetes Center,
      Syracuse, NY, in our "Living with Diabetes Class" (n=39). The two 3-h sessions
      offered comprehensive diabetes education by a diabetes nurse educator, dietitian,
      and exercise physiologist. These sessions were followed in 3 months by a 3-h
      follow-up class. Each group receiving tele-education consisted of two or three
      patients with diabetes. RESULTS: The hemoglobin A1c test (a blood test that
      estimates the overall average glucose levels over the past 3 months) improved in
      the face-to-face and the telemedicine groups. There was no significant change in
      weight between groups. Each group had significant improvements in scores on the
      Problem Areas In Diabetes survey, which is a measure of emotional functioning in
      diabetes. Diabetes treatment satisfaction as measured in the Diabetes Treatment
      Satisfaction Questionnaire improved in the face-to-face group but not in the
      telemedicine group. Although the face-to-face group had significantly higher
      scores in the Diabetes Treatment Satisfaction Questionnaire, the telemedicine
      group was highly satisfied with the services provided. CONCLUSIONS: Telemedicine
      offers an effective alternative approach for providing group diabetes education
      to individuals with poor access to diabetes education programs.

PMID- 22468985
TI  - Effects of multimodal nondrug therapy on dementia symptoms and need for care in
      nursing home residents with degenerative dementia: a randomized-controlled study
      with 6-month follow-up.
AB  - OBJECTIVES: To determine the efficacy of multimodal, nondrug therapy on symptoms
      of dementia and need for care in institutionalized individuals with degenerative
      dementia. DESIGN: Randomized, controlled, longitudinal trial. Data were analyzed
      using multiple linear regression. SETTING: Five German nursing homes.
      PARTICIPANTS: One hundred thirty-nine nursing home residents with primary
      degenerative dementia (Mini-Mental State Examination score < 24). INTERVENTION:
      The 6-month intervention comprised three components: motor stimulation,
      activities of daily living, and cognitive stimulation (MAKS). Groups of 10
      patients led by two therapists participated in the standardized intervention for
      2 hours, 6 days a week. The intervention was described in detail in an
      intervention manual. Adherence to the manual was high. Controls received
      treatment as usual. MEASUREMENTS: Overall geriatric symptoms were recorded using
      the Nurses' Observation Scale for Geriatric Patients, functional independence
      using the Barthel Index, and care time using the Resource Utilization in Dementia
      Formal Care. RESULTS: Of 646 individuals screened, 146 were eligible, and 130
      were included in the intention-to-treat analysis. At 6 months, results of the per
      protocol analysis (n = 119) showed improvement in overall dementia symptoms in
      the MAKS group and no change in the control group (adjusted mean difference (AMD)
      = -6.8, 95% confidence interval (CI) = -10.3 to -3.3; P < .001, Cohen d = 0.66).
      This effect was greatest on the social behavior (AMD = -1.9, 95% CI = -2.9 to 
      0.8; P < .001; Cohen d = 0.54) and instrumental activity of daily living (IADL)
      (AMD = -1.4, 95% CI = -2.5 to -0.30; P = .01; Cohen d = 0.43) subscales. No
      effect was seen on functional independence or total care time. CONCLUSION: This 6
      month nondrug multimodal intervention improved dementia symptoms in nursing home
      residents, especially in social behavior and IADL capabilities.

PMID- 22468986
TI  - FRET from quantum dots to photodecompose undesired acceptors and report the
      condensation and decondensation of plasmid DNA.
AB  - Protection of genes against enzymatic degradation and overcoming of cellular
      barriers are critical for efficient gene delivery. The effectiveness of gene
      delivery by nonviral vectors depends mostly on the extent of DNA packaging or
      condensation. We show that Forster resonance energy transfer (FRET)-mediated
      photodecomposition of undesired acceptors in doubly labeled plasmid DNA (pDNA)
      and FRET recovery after acceptor photodecomposition (FRET-RAP) are effective
      methods for the detection of DNA condensation and decondensation. Our hypothesis
      is that undesired acceptors within the Forster distance of highly-photostable
      donors in precondensed DNA can be selectively photodecomposed by FRET. We
      investigate this hypothesis by the random labeling of pcDNA3.1-GL3 and pUC18DNA
      with quantum dots (QDs) as the energy donor and AlexaFluor594 or Cy5 as the
      acceptor. At first, the random labeling generates efficient FRET, also called
      intrinsic FRET, in precondensed DNA, which prevents us from decoding any changes
      in the FRET efficiency during DNA condensation. Next, we suppressed the intrinsic
      FRET by the FRET-mediated photodecomposition of acceptors within the Forster
      distance of QDs. Conversely, many acceptors kept intact beyond the Forster
      distance provide us with high FRET efficiency during the condensation of pDNA
      using protamine. Further, the FRET efficiency is significantly decreased during
      the decondensation of DNA using heparan sulfate and glutathione. The random
      labeling of DNA using excess acceptors around photostable donors followed by the
      FRET-mediated photodecomposition of undesired acceptors can be a promising method
      for not only the sensitive detection of DNA condensation by FRET but also the
      customization of biomolecular sensors.

PMID- 22468987
TI  - Hypothermia-induced tyrosine phosphorylation of SIRPalpha in the brain.
AB  - Signal regulatory protein alpha (SIRPalpha) is a neuronal membrane protein that
      undergoes tyrosine phosphorylation in the brain of mice in response to forced
      swim (FS) stress in cold water, and this response is implicated in regulation of
      depression-like behavior in the FS test. We now show that subjection of mice to
      the FS in warm (37  degrees C) water does not induce the tyrosine phosphorylation
      of SIRPalpha in the brain. The rectal temperature (T(rec) ) of mice was reduced
      to 27 degrees  to 30  degrees C by performance of the FS for 10 min in cold
      water, whereas it was not affected by the same treatment in warm water. The level
      of tyrosine phosphorylation of SIRPalpha in the brain was increased by
      administration of ethanol or picrotoxin, starvation, or cooling after anesthesia,
      all of which also induced hypothermia. Furthermore, the tyrosine phosphorylation
      of SIRPalpha in cultured hippocampal neurons was induced by lowering the
      temperature of the culture medium. CD47, a ligand of SIRPalpha, as well as Src
      family kinases or SH2 domain-containing protein phosphatase 2 (Shp2), might be
      important for the basal and the hypothermia-induced tyrosine phosphorylation of
      SIRPalpha. Hypothermia is therefore likely an important determinant of both the
      behavioral immobility and tyrosine phosphorylation of SIRPalpha observed in the
      FS test.

PMID- 22468989
TI  - Ultrastructural and molecular characterization of a bacterial symbiosis in the
      ecologically important scale insect family Coelostomidiidae.
AB  - Scale insects are important ecologically and as agricultural pests. The majority
      of scale insect taxa feed exclusively on plant phloem sap, which is carbon rich
      but deficient in essential amino acids. This suggests that, as seen in the
      related aphids and psyllids, scale insect nutrition might also depend upon
      bacterial symbionts, yet very little is known about scale insect-bacteria
      symbioses. We report here the first identification and molecular characterization
      of symbiotic bacteria associated with the New Zealand giant scale Coelostomidia
      wairoensis, using fluorescence in situ hybridization (FISH), transmission
      electron microscopy (TEM) and 16S rRNA gene-based analysis. Dissection and FISH
      confirmed the location of the bacteria in large, paired, multilobate organs in
      the abdominal region of the insect. TEM indicated that the dominant pleomorphic
      bacteria were confined to bacteriocytes in the sheath-enclosed bacteriome.
      Phylogenetic analysis revealed the presence of three distinct bacterial types,
      the bacteriome-associated B-symbiont (Bacteroidetes), an Erwinia-related symbiont
      (Gammaproteobacteria) and Wolbachia sp. (Alphaproteobacteria). This study extends
      the current knowledge of scale insect symbionts and is the first microbiological
      investigation of the ecologically important coelostomidiid scales.

PMID- 22468988
TI  - Social support and crack/cocaine use among incarcerated mothers and nonmothers.
AB  - Limited research shows that correlates of substance use differ for mothers and
      nonmothers. This study compares mothers and nonmothers by examining the
      relationship between perceived social support and frequency of crack/cocaine use.
      Data for the 307 female prisoners in this sample were collected between 2007 and 
      2008  in four US states during the Criminal Justice-Drug Abuse Treatment Studies'
      (CJ-DATS) Reducing Risky Relationships for HIV protocol. Ordinary least squares
      regression models revealed that greater social support was significantly
      associated with less frequent crack/cocaine use among mothers but not nonmothers.
      Implications are discussed. This research was supported by the National Institute
      on Drug Abuse.

PMID- 22468990
TI  - Congenital infection of mice with Toxoplasma gondii induces minimal change in
      behavior and no change in neurotransmitter concentrations.
AB  - We examined the effect of maternal Toxoplasma gondii infection on behavior and
      the neurotransmitter concentrations of congenitally infected CD-1 mice at 4 and 8
      wk of age when latent tissue cysts would be present in their brains. Because of
      sex-associated behavioral changes that develop during aging, infected female mice
      were compared with control females and infected male mice were compared with
      control males. Only the short memory behavior (distance between goal box and
      first hole investigated) of male mice congenitally infected with T. gondii was
      significantly different (P < 0.05) from that of uninfected control males at both
      4 and 8 wk by using the Barnes maze test. The other parameters examined in the
      latter test, i.e., functional observational battery tests, virtual cliff, visual
      placement, and activity tests, were not significantly different (P > 0.05) at 4
      and 8 wk. Concentrations of neurotransmitters and their metabolites (dopamine;
      3,4-dihydroxyphenylacetic acid; homovanillic acid; norepinephrine; epinephrine; 3
      methoxy-4-hydroxyphenylglycol; serotonin; and 5-hydroxyindoleacetic acid) in the
      frontal cortex and striatum were not different (P > 0.05) between infected and
      control mice at 8 wk of age. The exact mechanism for the observed effect on short
      term memory in male mice is not known, and further investigation may help
      elucidate the molecular mechanisms associated with the proposed link between
      behavioral changes and T. gondii infection in animals. We were not able, however,
      to confirm the widely held belief that changes in neurotransmitters result from
      chronic T. gondii infection of the brain.

PMID- 22468991
TI  - Dispersion of alkyl-chain-functionalized reduced graphene oxide sheets in
      nonpolar solvents.
AB  - Alkyl chains were grafted onto reduced graphene oxide sheets to allow their
      dispersion in toluene, a common and representative nonpolar solvent. The grafting
      occurred on a variety of oxygen-containing functionalities already present on
      reduced graphene oxide, such as hydroxyl and epoxide groups. The structure and
      the defect density of the sheets were not significantly altered during the
      synthesis. When dispersed in water-toluene mixtures, phase transfer from the
      aqueous to the organic phase was observed upon grafting. In addition, the dry
      powder obtained readily disperses in common organic solvents without the
      assistance of any sonication treatment. 

PMID- 22468992
TI  - Understanding the differential impact of outcome monitoring: therapist variables
      that moderate feedback effects in a randomized clinical trial.
AB  - Providing outcome monitoring feedback to therapists seems to be a promising
      approach to improve outcomes in clinical practice. This study aims to examine the
      effect of feedback and investigate whether it is moderated by therapist
      characteristics. Patients (n=413) were randomly assigned to either a feedback or
      a no-feedback control condition. There was no significant effect of feedback in
      the full sample, but feedback was effective for not-on-track cases for therapists
      who used the feedback. Internal feedback propensity, self-efficacy, and
      commitment to use the feedback moderated the effects of feedback. The results
      demonstrate that feedback is not effective under all circumstances and therapist
      factors are important when implementing feedback in clinical practice.

PMID- 22468993
TI  - Stereotactic radiotherapy for malignancies involving the trigeminal and facial
      nerves.
AB  - Involvement of a cranial nerve caries a poor prognosis for many malignancies.
      Recurrent or residual disease in the trigeminal or facial nerve after primary
      therapy poses a challenge due to the location of the nerve in the skull base, the
      proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the
      resulting complex geometry. Surgical resection caries a high risk of morbidity
      and is often not an option for these patients. Stereotactic radiosurgery and
      radiotherapy are potential treatment options for patients with cancer involving
      the trigeminal or facial nerve. These techniques can deliver high doses of
      radiation to complex volumes while sparing adjacent critical structures. In the
      current study, seven cases of cancer involving the trigeminal or facial nerve are
      presented. These patients had unresectable recurrent or residual disease after
      definitive local therapy. Each patient was treated with stereotactic radiation
      therapy using a linear accelerator based system. A multidisciplinary approach
      including neuroradiology and surgical oncology was used to delineate target
      volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity.
      One patient who was reirradiated experienced cerebral radionecrosis with mild
      symptoms. Four of the seven patients treated had no evidence of disease after a
      median follow up of 12 months (range 2-24 months). A dosimetric analysis was
      performed to compare intensity modulated fractionated stereotactic radiation
      therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the
      brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the
      ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for
      the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies
      involving a cranial nerve requires a multidisciplinary approach. Use of an IM
      FSRT technique with a micro-multileaf collimator resulted in a lower dose to the
      brainstem, optic nerves and chiasm for each case examined.

PMID- 22468994
TI  - Comparison between prone and supine patient setup for spine stereotactic body
      radiosurgery.
AB  - This paper investigates the dosimetric characteristics of stereotactic body
      radiotherapy (SBRT) treatment plans of spine patients in the prone position
      compared to the supine position. A feasibility study for treating spine patients
      in the prone position using a fiducial-less tracking method is presented. One
      patient with a multilevel spinal metastasis was simulated for SBRT treatment in
      both the supine and prone position. CT scans of the patient were acquired, and
      treatment plans were created using the CyberKnife(r) planning platform. The
      potential advantage of the prone setup as a function of lesion location and
      number of vertebral bodies involved was studied for targets extending over 1, 2
      and 3 consecutive vertebral bodies in the thoracic and lumbar spine. The same
      process was repeated on an anthropomorphic phantom. A dose of 30 Gy in 5
      fractions was prescribed to 95% of the tumor volume and the dose to the cord was
      limited to 25 Gy. To investigate the feasibility of a fiducial-less tracking
      method in the prone setup, the patient was positioned prone on the treatment
      table and the spine motion was monitored as a function of time. Patient movement
      with the respiratory cycle was reduced by means of a belly-board. Plans in the
      prone and supine position achieved similar tumor coverage and sparing of the
      critical structures immediately adjacent to the spine (such as cord and
      esophagus). However, the prone plans systematically resulted in a lower dose to
      the normal structures located in the anterior part of the body (such as heart for
      thoracic cases; stomach, lower gastrointestinal tract and liver for lumbar
      cases). In addition, prone plans resulted in a lower number of monitor units
      compared to supine plans.

PMID- 22468995
TI  - A priori alignment of transtibial prostheses: a comparison and evaluation of
      three methods.
AB  - PURPOSE: The objectives of this study were to compare three a priori alignment
      methods and evaluate them based on initial gait quality and further alignment
      changes required to optimize gait. A priori alignment is requisite for monolimbs,
      transtibial prostheses in which the socket and pylon are made from one piece of
      plastic, because monolimbs have no alignment adjustability. METHOD: The three
      methods investigated were traditional bench alignment (TRAD), vertical alignment
      axis (VAA) and anatomical based alignment (ABA). Endoskeletal components were
      utilized for the study, rather than monolimbs, so that alignment could be
      experimentally manipulated. Three endoskeletal prostheses were aligned, one
      according to each a priori method, for each of seven subjects. Gait and alignment
      data were captured, dynamic alignment was performed to optimize gait, and data
      were captured again. RESULTS: VAA and TRAD methods required less change compared
      to ABA in socket flexion angle. Looking at subjects individually, VAA produced a
      better alignment and better gait for the greatest number of subjects.
      CONCLUSIONS: A new refined method of a priori alignment is proposed based on the
      results of this study, and is applicable for a priori alignment of monolimbs or
      any type of transtibial prosthesis.

PMID- 22468996
TI  - Fecal transplant against relapsing Clostridium difficile-associated diarrhea in
      32 patients.
AB  - Clostridium difficile-associated disease (CDAD) with frequent watery stools,
      sometimes with painful bowel movements, fever and sickness, is probably the major
      known cause of antibiotic-associated diarrhea and colitis, most probably
      depending on a disruption of the normal intestinal balance in the microbiome. In
      this study, we have inoculated a mixture of fecal microbes--as an enema-
      originating from a healthy Scandinavian middle-aged donor, regularly re
      cultivated under strict anaerobic conditions for more than 10 years, to 32
      patients. Twenty-two patients (69%) were durably cured. In those patients
      receiving the transplant by colonoscopy, four out of five were cured. To the best
      of our knowledge, this is the first time a fecal culture of microbes has retained
      the possibility for years to cure a substantial number of patients with CDAD.

PMID- 22468998
TI  - Treatment of nuclear-donor cells or cloned zygotes with chromatin-modifying
      agents increases histone acetylation but does not improve full-term development
      of cloned cattle.
AB  - Although somatic cell nuclear transfer (SCNT) is a promising tool, its potential
      use is hampered by the high mortality rates during the development to term of
      cloned offspring. Abnormal epigenetic reprogramming of donor nuclei after SCNT is
      thought to be the main cause of this low efficiency. We hypothesized that
      chromatin-modifying agents (CMAs) targeting chromatin acetylation and DNA
      methylation could alter the chromatin configuration and turn them more amenable
      to reprogramming. Thus, bovine fibroblasts were treated with 5-aza-2'
      deoxycytidine (AZA) plus trichostatin (TSA) or hydralazine (HH) plus valproic
      acid (VPA) whereas, in another trial, cloned bovine zygotes were treated with
      TSA. The treatment of fibroblasts with either AZA+TSA or HH+VPA increased histone
      acetylation, but did not affect the level of DNA methylation. However, treatment
      with HH+VPA decreased cellular viability and proliferation. The use of these
      cells as nuclear donors showed no positive effect on pre- and postimplantation
      development. Regarding the treatment of cloned zygotes with TSA, treated one-cell
      embryos showed an increase in the acetylation patterns, but not in the level of
      DNA methylation. Moreover, this treatment revealed no positive effect on pre- and
      postimplantation development. This work provides evidence the treatment of either
      nuclear donor cells or cloned zygotes with CMAs has no positive effect on pre-
      and postimplantation development of cloned cattle.

PMID- 22469000
TI  - Reorganization of intramolecular high frequency vibrational modes and dynamic
      solvent effect in electron transfer reactions.
AB  - The possibility of the multichannel stochastic model to adequately describe all
      principal regularities observed in thermal electron transfer kinetics has been
      demonstrated. The most important are as follows: (i) the model predicts the
      solvent controlled regime in the Marcus normal region and its almost full
      suppression in the Marcus inverted region as well as a continuous transition
      between them in the vicinity of the activationless region; (ii) the suppression
      of dynamic solvent effect (DSE) is principally caused by the reorganization of
      high frequency vibrational modes; (iii) an additional factor of the DSE
      suppression stems from fast solvent relaxation component; (iv) in the inverted
      region, the multichannel stochastic model predicts the apparent activation energy
      to be much less than that calculated with Marcus equation. The exploration of the
      multichannel stochastic model has allowed one to conclude that the reorganization
      of high frequency vibrational modes can (i) raise the maximum rate constant above
      the solvent controlled limit by 2 and more orders of magnitude, (ii) shift the
      rate constant maximum to larger values of the free energy gap, and (iii) approach
      the electron transfer kinetics to the nonadiabatic regime.

PMID- 22468997
TI  - Early aberrations in chromatin dynamics in embryos produced under in vitro
      conditions.
AB  - In vitro production of porcine embryos by means of in vitro fertilization (IVF)
      or somatic cell nuclear transfer (SCNT) is limited by great inefficienciy. The
      present study investigated chromatin and nucleolar dynamics in porcine embryos
      developed in vivo (IV) and compared this physiological standard to that of
      embryos produced by IVF, parthenogenetic activation (PA), or SCNT. In contrast to
      IV embryos, chromatin spatial and temporal dynamics in PA, IVF, and SCNT embryos
      were altered; starting with aberrant chromatin-nuclear envelope interactions at
      the two-cell stage, delayed chromatin decondensation and nucleolar development at
      the four-cell stage, and ultimately culminating in failure of proper first
      lineage segregation at the blastocyst stage, demonstrated by poorly defined inner
      cell mass. Interestingly, in vitro produced (IVP) embryos also lacked a
      heterochromatin halo around nucleolar precursors, indicating imperfections in
      global chromatin remodeling after fertilization/activation. Porcine IV-produced
      zygotes and embryos display a well-synchronized pattern of chromatin dynamics
      compatible with genome activation and regular nucleolar formation at the four
      cell stage. Production of porcine embryos under in vitro conditions by IVF, PA,
      or SCNT is associated with altered chromatin remodeling, delayed nucleolar
      formation, and poorly defined lineage segregation at the blastocyst stage, which
      in turn may impair their developmental capacity.

PMID- 22468999
TI  - Discovery and optimization of a novel spiropyrrolidine inhibitor of beta
      secretase (BACE1) through fragment-based drug design.
AB  - The aspartyl protease beta-secretase, or BACE, has been demonstrated to be a key
      factor in the proteolytic formation of Abeta-peptide, a major component of
      plaques in the brains of Alzheimer's disease (AD) patients, and inhibition of
      this enzyme has emerged as a major strategy for pharmacologic intervention in AD.
      An X-ray-based fragment screen of Pfizer's proprietary fragment collection has
      resulted in the identification of a novel BACE binder featuring spiropyrrolidine
      framework. Although exhibiting only weak inhibitory activity against the BACE
      enzyme, the small compound was verified by biophysical and NMR-based methods as a
      bona fide BACE inhibitor. Subsequent optimization of the lead compound, relying
      heavily on structure-based drug design and computational prediction of
      physiochemical properties, resulted in a nearly 1000-fold improvement in potency
      while maintaining ligand efficiency and properties predictive of good
      permeability and low P-gp liability.

PMID- 22469001
TI  - The mitochondrial genome of Malus domestica and the import-driven hypothesis of
      mitochondrial genome expansion in seed plants.
AB  - Mitochondrial genomes of spermatophytes are the largest of all organellar
      genomes. Their large size has been attributed to various factors; however, the
      relative contribution of these factors to mitochondrial DNA (mtDNA) expansion
      remains undetermined. We estimated their relative contribution in Malus domestica
      (apple). The mitochondrial genome of apple has a size of 396 947 bp and a one to
      nine ratio of coding to non-coding DNA, close to the corresponding average values
      for angiosperms. We determined that 71.5% of the apple mtDNA sequence was highly
      similar to sequences of its nuclear DNA. Using nuclear gene exons, nuclear
      transposable elements and chloroplast DNA as markers of promiscuous DNA content
      in mtDNA, we estimated that approximately 20% of the apple mtDNA consisted of DNA
      sequences imported from other cell compartments, mostly from the nucleus. Similar
      marker-based estimates of promiscuous DNA content in the mitochondrial genomes of
      other species ranged between 21.2 and 25.3% of the total mtDNA length for grape,
      between 23.1 and 38.6% for rice, and between 47.1 and 78.4% for maize. All these
      estimates are conservative, because they underestimate the import of non
      functional DNA. We propose that the import of promiscuous DNA is a core mechanism
      for mtDNA size expansion in seed plants. In apple, maize and grape this mechanism
      contributed far more to genome expansion than did homologous recombination. In
      rice the estimated contribution of both mechanisms was found to be similar.

PMID- 22469002
TI  - Cardiovascular toxicity associated with small molecule tyrosine kinase inhibitors
      currently in clinical use.
AB  - INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have changed the concepts of
      systemic therapy for a variety of advanced solid and hematologic malignancies.
      However, their toxicity can be significant, and includes both cardiac and non
      cardiac effects. AREAS COVERED: The authors evaluate comprehensively the adverse
      cardiovascular portfolio of small molecule TKIs, postulate their underlying
      mechanisms and offer recommendations regarding prevention and therapy of these
      toxicities. EXPERT OPINION: For most pan-selective TKIs, there might not be a
      clear-cut relationship between specific patterns of TK inhibition and
      cardiovascular toxicity. Cardiovascular side effects are likely due to
      dysregulation of multiple kinase regulated pathways. The cardiovascular effects
      of small molecule TKIs include peripheral edema and congestive heart failure,
      systemic and pulmonary hypertension, acute coronary syndromes and cardiac arrest
      due to QTc prolongation. Caution should be sought in patients with pre-existing
      cardiac dysfunction before initiating any of these agents. It is hoped that newer
      TKI generations will display minimal if any cardiovascular toxicity, while
      maintaining their anticancer efficacy. As of today, the high likelihood of
      morbidity without treatment mandates that cardiovascular toxicity of TKIs be
      carefully assessed and balanced with the known benefits of administering these
      agents.

PMID- 22469003
TI  - Spectroscopic characterization and modeling of quadrupolar charge-transfer dyes
      with bulky substituents.
AB  - Joint experimental and theoretical work is presented on two quadrupolar D-pi-A-pi
      D chromophores characterized by the same bulky donor (D) group and two different
      central cores. The first chromophore, a newly synthesized species with a
      malononitrile-based acceptor (A) group, has a V-shaped structure that makes its
      absorption spectrum very broad, covering most of the visible region. The second
      chromophore has a squaraine-based core and therefore a linear structure, as also
      evinced from its absorption spectra. Both chromophores show an anomalous red
      shift of the absorption band upon increasing solvent polarity, a feature that is
      ascribed to the large, bulky structure of the molecules. For these molecules, the
      basic description of polar solvation in terms of a uniform reaction field fails.
      Indeed, a simple extension of the model to account for two independent reaction
      fields associated with the two molecular arms quantitatively reproduces the
      observed linear absorption and fluorescence as well as fluorescence anisotropy
      spectra, fully rationalizing their nontrivial dependence on solvent polarity. The
      model derived from the analysis of linear spectra is adopted to predict nonlinear
      spectra and specifically hyper-Rayleigh scattering and two-photon absorption
      spectra. In polar solvents, the V-shaped chromophore is predicted to have a large
      HRS response in a wide spectral region (approximately 600-1300 nm). Anomalously
      large and largely solvent-dependent HRS responses for the linear chromophores are
      ascribed to symmetry lowering induced by polar solvation and amplified in this
      bulky system by the presence of two reaction fields. 

PMID- 22469004
TI  - Genome modifications in plant cells by custom-made restriction enzymes.
AB  - Genome editing, i.e. the ability to mutagenize, insert, delete and replace
      sequences, in living cells is a powerful and highly desirable method that could
      potentially revolutionize plant basic research and applied biotechnology. Indeed,
      various research groups from academia and industry are in a race to devise
      methods and develop tools that will enable not only site-specific mutagenesis but
      also controlled foreign DNA integration and replacement of native and transgene
      sequences by foreign DNA, in living plant cells. In recent years, much of the
      progress seen in gene targeting in plant cells has been attributed to the
      development of zinc finger nucleases and other novel restriction enzymes for use
      as molecular DNA scissors. The induction of double-strand breaks at specific
      genomic locations by zinc finger nucleases and other novel restriction enzymes
      results in a wide variety of genetic changes, which range from gene addition to
      the replacement, deletion and site-specific mutagenesis of endogenous and
      heterologous genes in living plant cells. In this review, we discuss the
      principles and tools for restriction enzyme-mediated gene targeting in plant
      cells, as well as their current and prospective use for gene targeting in model
      and crop plants.

PMID- 22469005
TI  - T-cell phenotypes in bronchoalveolar lavage fluid, blood and lymph nodes in
      pulmonary sarcoidosis--indication for an airborne antigen as the triggering
      factor in sarcoidosis.
AB  - BACKGROUND: An increased percentage of CD4+ T cells is usually observed in
      bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis. In HLA
      DRB1*03-positive patients, such T cells express the T-cell receptor (TCR) AV2S3+
      gene segment. It is not known whether cells found in BALF reflect those in
      enlarged regional lymph nodes (LNs). Therefore, the aim of this study was to
      compare T-cell phenotypes in BALF, blood and mediastinal LNs. METHODS: Fifteen
      patients underwent clinical investigation including bronchoscopy with
      bronchoalveolar lavage. Blood samples were drawn, and endoscopic ultrasound
      guided fine-needle aspiration of enlarged mediastinal LNs was performed via the
      oesophagus. T cells from all three compartments were analysed by flow cytometry
      for markers of activity, differentiation and T regulatory function. RESULTS: The
      CD4/CD8 ratio was significantly higher in BALF compared with regional LNs and was
      also significantly higher in LNs than in blood. The CD4+ T cells were recently
      activated and more differentiated in BALF than in blood and LNs. There was an
      accumulation of T regulatory cells (FOXP3+) in LNs and a correlation between high
      levels of FOXP3+ cells in BALF and in LNs. In HLA-DRB1*03-positive patients, TCR
      AV2S3+ CD4+ T cells were predominantly localized within BALF. CONCLUSIONS: The
      CD4+ T-cell phenotype in BALF indicates an active ongoing specific immune
      response primarily localized to the alveolar space.

PMID- 22469006
TI  - Experiment on formulation and drug release behavior of porosity asymmetric
      membrane capsules in vitro.
AB  - Porosity asymmetric membrane capsules were prepared to study the relationship
      between the capsule formulation and drug release. Cellulose acetate (CA) and pore
      formers were used in the capsule shell formulation as the main semipermeable
      membrane material. The capsules were permeable to both water and dissolved
      solutes. Using sparingly soluble drug acetaminophen as a model, cumulative
      release was calculated. The slope of the release profile from the distilled water
      had good relationship with the concentration of the pore formers F68. The release
      of acetaminophen was independent to the pH, osmotic pressure of dissolution
      medium, but influenced by intensity of agitation. When the concentration of pore
      former was low, zero-order release behavior was observed within 24 h which was
      consistent with Fickian diffusion model. When the concentration of pore former
      was high, however, Higuchi model release was found which is caused by Fickian
      diffusion and osmotic pressure release. With scanning electron microscope (SEM),
      the surface structure and cross-section of the capsule shell were also studied
      before and after drug delivery. With simple preparation and broad scope of drug
      application, porosity asymmetric membrane capsules can give desired drug extended
      release and show more convenience than controlled tablets with laser drilling.

PMID- 22469007
TI  - Healthy birth after testicular extraction of sperm and ICSI from an azoospermic
      man with mild androgen insensitivity syndrome caused by an androgen receptor
      partial loss-of-function mutation.
AB  - CONTEXT: The androgen receptor (AR) is essential for the development and
      maintenance of the male phenotype, and for spermatogenesis. Mutations in the AR
      gene cause a wide variety of androgen insensitivity syndromes (AIS), ranging from
      complete feminization to phenotypic males with infertility. OBJECTIVE: We report
      the first birth achieved after intracytoplasmic sperm injection (ICSI) with sperm
      from an azoospermic man with an AR mutation associated with mild AIS (MAIS).
      PATIENTS AND METHODS: A couple with primary infertility was referred to our
      centre. The man had azoospermia with testicular hypotrophy and an undervirilized
      phenotype despite a normal plasma testosterone level. His androgen sensitivity
      index and serum anti-mullerian hormone (AMH) levels were elevated, pointing to
      AIS. Molecular analysis of the AR gene revealed a point mutation resulting in an
      F754S substitution (renumbered F755S in the 2012 McGill University AR gene
      database), in the ligand-binding domain of the protein, and further analysis
      indicated impaired receptor function. RESULTS: After genetic counselling of the
      couple, oocytes were retrieved after controlled ovarian hyperstimulation, and
      sperm were obtained simultaneously by testicular extraction for ICSI. Nine
      embryos were obtained. Two were transferred and two were suitable for
      cryopreservation. A pregnancy was obtained and a healthy girl, carrying the F754S
      AR mutation, was born at 37 weeks of gestation. AR and AMH were detected by
      immunohistochemistry in the patient's testicular specimens. AMH immuno-staining
      was intense in tubules without spermatogenesis and weak in those with ongoing
      spermatogenesis. CONCLUSION: A healthy child can be obtained by testicular
      extraction and ICSI despite azoospermia in MAIS. The parents must be informed of
      the X-linked transmission of the mutation to their descendants. The relationship
      between AR signalling, testicular AMH expression and spermatogenesis in this
      patient is discussed.

PMID- 22469008
TI  - Believing is seeing: an evolving research program on patients' psychotherapy
      expectations.
AB  - In this article I discuss one facet of my evolving research program focused on
      patients' psychotherapy-related expectations. Although generally considered a
      common psychotherapeutic factor, expectations have been historically undervalued
      conceptually, empirically, and clinically. Attempting to somewhat redress this
      slight, I will (a) define the various forms of patients' psychotherapy-related
      expectations, (b) present relevant findings from research that my colleagues,
      students, and I have conducted, (c) summarize an integrative psychotherapy
      approach that underscores expectations as an explanatory construct for patients'
      corrective experiences, and (d) highlight future research directions for
      increasing our understanding of the nature and functions of the expectancy
      construct.

PMID- 22469009
TI  - Domain wall motion in synthetic Co2Si nanowires.
AB  - We report the synthesis of single crystalline Co(2)Si nanowires and the
      electrical transport studies of single Co(2)Si nanowire devices at low
      temperature. The butterfly shaped magnetoresistance shows interesting
      ferromagnetic features, including negative magnetoresistance, hysteretic switch
      fields, and stepwise drops in magnetoresistance. The nonsmooth stepwise
      magnetoresistance response is attributed to magnetic domain wall pinning and
      depinning motion in the Co(2)Si nanowires probably at crystal or morphology
      defects. The temperature dependence of the domain wall depinning field is
      observed and described by a model based on thermally assisted domain wall
      depinning over a single energy barrier.

PMID- 22469010
TI  - Genomic analysis of emm59 group A Streptococcus invasive strains, United States.
AB  - Genomic analysis of type emm59 group A Streptococcus invasive strains isolated in
      the United States discovered higher than anticipated genetic heterogeneity among
      strains and identified a heretofore unrecognized monoclonal cluster of invasive
      infections in the San Francisco Bay area. Heightened monitoring for a potential
      shift in the epidemic behavior of emm59 group A Streptococcus is warranted.

PMID- 22469011
TI  - Prevalence and risk factors associated with Leptospira spp. infection in
      technified swine farms in the state of Alagoas, Brazil: risk factors associated
      with Leptospira spp. in swine farms.
AB  - The aim of this study was to determine the prevalence and to identify the risk
      factors associated with Leptospira spp. infection in technified pig farms in the
      state of Alagoas, Brazil. To compose sample for the prevalence study, 342 pigs
      were used (312 sows and 30 boars) proceeding from seven swine farms distributed
      in five districts of the state of Alagoas, Brazil. The infection's serological
      diagnosis was performed by microscopic agglutination test. The risk factors
      analysis was performed using research questionnaires consisting of objective
      questions related to the breeder, the general characteristics of the property,
      and the productive, reproductive and sanitary management. Prevalence of 16.1%
      (55/342) of pigs seropositive was obtained. The associated risk factors were not
      performing quarantine (P = 0.003, OR = 5.43, CI = 1.79-16.41) and the use of
      artificial insemination (P = 0.023, OR = 3.38, CI = 1.18-9.66). A significant
      association of sow infection with the increased number of stillborn and mummified
      foetuses was found, as well as with the increased frequency of oestrus recurrence
      and the increased weaning-to-oestrus interval of seropositive sows. One might
      state that Leptospira spp. infection is disseminated in technified pig farms in
      the State of Alagoas, favouring reproductive failures and the impairment of
      zootechnical performance in these properties. The risk factors identified in this
      study are facilitators in the infecting agent dissemination and should be
      adjusted to control the disease in the herds studied.

PMID- 22469012
TI  - Modulation of metallophilic bonds: solvent-induced isomerization and luminescence
      vapochromism of a polymorphic Au-Cu cluster.
AB  - We report a homoleptic Au-Cu alkynyl cluster that represents an unexplored class
      of luminescent materials with stimuli-responsive photophysical properties. The
      bimetallic complex formulated as [Au(2)Cu(2)(C(2)OHC(5)H(8))(4)](n) efficiently
      self-assembles from Au(SC(4)H(8))Cl, Cu(NCMe)(4)PF(6), and 1-ethynylcyclopentanol
      in the presence of NEt(3). This compound shows remarkably diverse polymorphism
      arising from the modulation of metallophilic interactions by organic solvents.
      Four crystalline forms, obtained from methanol (1a); ethanol, acetone, or
      choloroform (1b); toluene (1c); and diethyl ether or ethyl acetate (1d),
      demonstrate different photoluminescent characteristics. The solid-state quantum
      yields of phosphorescence (Phi) vary from 0.1% (1a) to 25% (1d), depending on the
      character of intermetallic bonding. The structures of 1b-d were determined by
      single-crystal X-ray diffraction. The ethanol (1b, Phi = 2%) and toluene (1c, Phi
      = 10%) solvates of [Au(2)Cu(2)(C(2)OHC(5)H(8))(4)](n) adopt octanuclear isomeric
      structures (n = 2), while 1d (Phi = 25%) is a solvent-free chain polymer built
      from two types of Au(4)Cu(4) units. Electronic structure calculations show that
      the dramatic enhancement of the emission intensity is correlated with the
      increasing role of metal-metal bonding. The latter makes the emission
      progressively more metal-centered in the order 1b < 1c < 1d. The metallophilic
      contacts in 1a-d show high sensitivity to the vapors of certain solvents, which
      effectively induce unusual solid-state isomerization and switching of the
      absorption and luminescence properties via non-covalent interactions. The
      reported polymorphic material is the first example of a gold(I) alkynyl compound
      demonstrating vapochromic behavior.

PMID- 22469013
TI  - TiO2 derived by titanate route from electrospun nanostructures for high
      performance dye-sensitized solar cells.
AB  - We report the use of highly porous, dense, and anisotropic TiO(2) derived from
      electrospun TiO(2)-SiO(2) nanostructures through titanate route in dye-sensitized
      solar cells. The titanate-derived TiO(2) of high surface areas exhibited superior
      photovoltaic parameters (efficiency > 7%) in comparison to the respective
      electrospun TiO(2) nanomaterials and commercially available P-25.

PMID- 22469014
TI  - Identification and functional screening of microRNAs highly deregulated in
      colorectal cancer.
AB  - MicroRNAs (miRNAs) constitute a robust regulatory network with post
      transcriptional regulatory efficiency for almost one half of human coding genes,
      including oncogenes and tumour suppressors. We determined the expression profile
      of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoural tissues
      and identified 42 differentially expressed miRNAs. We chose miR-215, miR-375, miR
      378, miR-422a and miR-135b for further validation on an independent cohort of 125
      clinically characterized CRC patients and for in vitro analyses. MiR-215, miR
      375, miR-378 and miR-422a were significantly decreased, whereas miR-135b was
      increased in CRC tumour tissues. Levels of miR-215 and miR-422a correlated with
      clinical stage. MiR-135b was associated with higher pre-operative serum levels of
      CEA and CA19-9. In vitro analyses showed that ectopic expression of miR-215
      decreases viability and migration, increases apoptosis and promotes cell cycle
      arrest in DLD-1 and HCT-116 colon cancer cell lines. Similarly, overexpression of
      miR-375 and inhibition of miR-135b led to decreased viability. Finally,
      restoration of miR-378, miR-422a and miR-375 inhibited G1/S transition. These
      findings indicate that miR-378, miR-375, miR-422a and miR-215 play an important
      role in CRC as tumour suppressors, whereas miR-135b functions as an oncogene;
      both groups of miRNA contribute to CRC pathogenesis.

PMID- 22469015
TI  - Tuberculosis screening before anti-hepatitis C virus therapy in prisons.

PMID- 22469016
TI  - Prediction of functional disability by depressive state among community-dwelling
      elderly in Japan: a prospective cohort study.
AB  - AIM: We carried out a prospective cohort study to evaluate the risk factors of
      functional disability by depressive state. METHODS: A total of 783 men and women,
      aged 70 years and over, participated in this study. We followed the participants
      in terms of the onset of functional disability by using a public long-term care
      insurance database. The Geriatric Depression Scale (GDS) was used to measure
      depressive state. Age, sex, history of chronic disease, living alone, fall
      experience, cognitive impairment, instrumental activities of daily living (IADL),
      the Motor Fitness Scale (MFS), frequency of going out and social support at
      baseline were used as the main covariates. The Cox regression analysis was used
      to examine the difference in functional disability stratified according to
      depressive state. RESULTS: The incidence of functional disability was 38 persons
      in the non-depression group and 42 persons in the depression group (RR 2.34; 95%
      CI 1.46-3.79). The results of the depression group showed a significant
      difference in cognitive impairment (HR 3.51; 95% CI 1.39-8.85), MFS (HR 5.60; 95%
      CI 1.32-23.81) and IADL (HR 3.37; 95% CI 1.65-6.85). The results of the non
      depression group showed a significant difference in MFS (HR 2.97; 95% CI 1.47
      6.96), and frequency of going out (HR 3.21; 95% CI 1.47-6.96). CONCLUSIONS: In
      conclusion, risk factors for functional disability were found to differ on the
      basis of whether or not community-dwelling elderly individuals experience
      depressive state. The type of support offered must be based on whether or not
      depressive state is present.

PMID- 22469017
TI  - Basophil response and the induction of a tolerance in venom immunotherapy: a long
      term sting challenge study.
AB  - BACKGROUND: There is no in vitro test to predict the induction of long-term
      tolerance in patients treated with venom immunotherapy (VIT). The aim of this
      study was to investigate whether immunotherapy-induced changes in basophil
      responsiveness reflect a state of protection and the induction of a tolerance.
      METHODS: Twenty-three patients with allergic reaction after Hymenoptera sting (11
      wasp and 12 honeybee) were treated with VIT. In all patients, a CD63 basophil
      activation test was performed before the beginning of immunotherapy, after 1 year
      and after completing 4-6.5 years of immunotherapy (approximately 1 year after
      stopping). The tolerance was then evaluated by a sting challenge test. The
      basophil activation test was repeated 3-6 months after the challenge. RESULTS:
      Twenty-two subjects showed a negative sting challenge, and one subject, a
      positive sting challenge. Allergen-specific basophil response remained unchanged
      after 1 year of immunotherapy. However, after immunotherapy, a significant and
      approximately fourfold decrease was demonstrated in all tolerant subjects mainly
      in response to submaximal 0.1 MUg/ml allergen concentration. This depression was
      sustained and did not change with the sting challenge test. In a nontolerant
      patient with a positive sting challenge, basophil response did not change.
      CONCLUSIONS: Our results suggest that the depression of allergen-specific
      basophil response seems to be associated with the induction of a tolerance after
      completing a course of VIT.

PMID- 22469018
TI  - Cerebrospinal fluid alpha-synuclein levels are elevated in multiple sclerosis and
      neuromyelitis optica patients during replase.
AB  - The concept that the immune system plays a central role in the pathogenesis of
      multiple sclerosis (MS) and neuromyelitis optica (NMO) was indisputable. However,
      neurodegenerative pathological features including loss of axons and neurons were
      also found in the lesions of these diseases. alpha-Synuclein is one of the most
      abundant proteins in pre-synaptic terminals. Recently, many research show alpha
      synuclein level in CSF may reflect the progression of synaptic dysfunction and
      neuronal apoptosis. Whether the levels of CSF alpha-synuclein are changed in MS
      and NMO patients remain unknown. In this study, CSF alpha-synuclein was measured
      by an enzyme-linked immunosorbent assay (ELISA) in MS (n = 18) patients, NMO (n =
      22) patients, Parkinson's disease patients (n = 9), and the controls (n = 11). We
      found concentration of alpha-synuclein in MS and NMO patients were significantly
      higher than Parkinson's disease subgroup and the controls. Both MS and NMO
      revealed an increased disease disability with increased CSF alpha-synuclein.
      Thus, CSF alpha-synuclein may be reflect injure axons and neurons in inflammatory
      demyelinating diseases.

PMID- 22469020
TI  - A qualitative and quantitative study of the surgical and rehabilitation response
      to the earthquake in Haiti, January 2010.
AB  - BACKGROUND: The disaster response environment in Haiti following the 2010
      earthquake represented a complex healthcare challenge. This study was designed to
      identify challenges during the Haiti disaster response. METHODS: Qualitative and
      quantitative study of injured patients carried out six months after the January
      2010 earthquake in Haiti to review the surgical inputs of foreign medical teams.
      RESULTS: Study findings revealed a need during the response for improved medical
      records and data gathering for regulation, quality assurance, coordination and
      resource allocation; wider adherence to standard patient referral mechanisms and
      protocols linking surgical service provision with appropriate hospital and
      community based rehabilitation services; a greater recognition of the impact of
      non-amputation injury, and the need for patients to have a greater say in their
      management and to be the keepers of their medical records. Key first steps to
      improving the international response are a minimum dataset and uniform reporting.
      CONCLUSION: This study showed that challenges for emergency medical response
      during the Haiti Earthquake involved issues of accountability, professional
      ethics, standards-of-care, unmet needs, patient agency and expected outcomes for
      patients in such settings:

PMID- 22469019
TI  - Comparison of ectomycorrhizal communities in natural and cultivated Tuber
      melanosporum truffle grounds.
AB  - Truffles are hypogeous ectomycorrhizal (EM) fungi belonging to the genus Tuber.
      Although outplanting of truffle-inoculated host plants has enabled the
      realization of productive orchards, truffle cultivation is not yet standardized.
      Therefore, monitoring the distribution of fungal species in different truffle
      fields may help us to elucidate the factors that shape microbial communities and
      influence the propagation and fruiting of Tuber spp. In this study, we compared
      the fungal biodiversity in cultivated and natural Tuber melanosporum truffle
      fields located in Central Italy. To this end, ectomycorrhizas (ECM) and soil
      samples were molecularly analyzed, and an inventory of the fungi associated with
      Quercus pubescens plants colonized by T. melanosporum, Tuber aestivum or Tuber
      brumale was compiled. T. melanosporum and T. aestivum were dominant on the
      cultivated plants, and the number of EM species was markedly lower in the
      cultivated sites than in the natural sites. However, in the same site, EM
      biodiversity was higher in T. brumale-colonized plants than in T. melanosporum
      colonized plants. These results suggest that different Tuber spp. may have
      different competitive effects on the other mycobionts. Additionally, in keeping
      with our previous findings, we found that the number of T. melanosporum genotypes
      recovered from the soil samples was higher than that of the underlying ECM.

PMID- 22469021
TI  - Uterine artery embolisation: challenges and opportunities in cross-specialty
      care.

PMID- 22469022
TI  - Re: Atherton MJ, Daborn JP, Tsokos N, Jeffery JT & Yin MJ, Complications
      associated with tissue anchor migration after vaginal surgery using the tissue
      fixation system - a case series, ANZJOG 2012; 52 (1): 83-86.

PMID- 22469025
TI  - Activating KIR/HLA complexes in classic Kaposi's Sarcoma.
AB  - BACKGROUND: Classic Kaposi's Sarcoma (cKS) is a rare vascular tumor associated
      with Human Herpesvirus 8 (KSHV) infection, nevertheless not all KSHV-infected
      individuals have cKS. OBJECTIVE: We investigated whether particular KIR/HLA
      receptor/ligand genotypes would be preferentially present in KSHV-infected and
      uninfected individuals who have or have not developed cKS. METHODS: KIR/HLA
      genotypes were analyzed by molecular genotyping in 50 KSHV-infected individuals
      who did or did not have cKS and in 33 age-and sex-matched KSHV seronegative
      individuals. RESULTS: There was no association of individual KIR, HLA or receptor
      ligand combinations with KSHV infection. However, activating KIR and KIR/HLA
      genotypes were significantly more frequent in cKS cases, specifically KIR3DS1,
      KIR2DS1, and KIR2DS1 with its HLA-C2 ligand. CONCLUSION: A nonspecific
      inflammatory response triggered by activation of NK cells upon KIR-HLA
      interaction could be associated with the pathogenesis of KS.

PMID- 22469026
TI  - Three-years clinical outcome of immediate provisionalization of single
      Osseospeed(TM)  implants in extraction sockets and healed ridges.
AB  - AIM: The purpose of this prospective multicenter clinical study was to compare 3
      years implant survival, bone and soft tissue changes following immediate loading
      using single Osseospeed(TM)  implants (Astra Tech AB, Molndal, Sweden) installed
      in healed ridges or extraction sockets. MATERIAL AND METHODS: Implants were
      provisionally restored the day of surgery using cemented acrylic crowns out of
      full occlusion. The provisional crowns were replaced after 12 weeks by full
      ceramic crowns. Implant survival, bone levels, soft tissue levels and peri
      implant health were monitored up to 3 years. RESULTS: 55 patients (22 men, 33
      women; mean age 45) had the implant installed in extraction sockets and 58
      patients (25 men, 33 women; mean age 42) received conventional implant treatment
      in healed ridges. Three implants failed in the extraction group and one implant
      failed in the healed group, all failures occurred before the final crown
      placement. No further losses occurred during 3 years, giving a statistically
      comparable survival rate of 94.6% and 98.3%, respectively. The total bone loss
      after 3 years, compared to implant placement was 0.4 mm (SD 1.5) in healed sites,
      whilst the immediate sites showed a bone gain of 1.6 mm (SD 2.4) due to bone fill
      in the alveolus. Papillae retracted with 0.3 and 0.0 mm in the period of
      provisionalization, but grew back after final crown was placed with 0.3 and 0.5
      mm in extraction and healed sites respectively after 3 years. Plaque and
      inflammation scores were very low throughout the study time, irrespective of
      treatment modality. CONCLUSIONS: Immediate implants restored at the day of
      surgery show comparable risk for implant failure, bone loss and midfacial soft
      tissue recession compared to conventionally installed implants. The 3-years
      results suggest both hard and soft tissue stability.

PMID- 22469027
TI  - Thermodynamic modeling of ionic liquid systems: development and detailed overview
      of novel methodology based on the PC-SAFT.
AB  - We present the results of an extensive study on a novel approach of modeling
      ionic liquids (ILs) and their mixtures with molecular compounds, incorporating
      perturbed-chain statistical associating fluid theory (PC-SAFT). PC-SAFT was used
      to calculate the thermodynamic properties of different homologous series of ILs
      based on the bis(trifluormethylsulfonyl)imide anion ([NTf2]). First, pure fluid
      parameters were obtained for each IL by means of fitting the model predictions to
      experimental liquid densities over a broad range of temperature and pressure. The
      reliability and physical significance of the parameters as well as the employed
      molecular scheme were tested by calculation of density, vapor pressure, and other
      properties of pure ILs (e.g., critical properties, normal boiling point).
      Additionally, the surface tension of pure ILs was calculated by coupling the PC
      SAFT equation of state with density gradient theory (DGT). All
      correlated/predicted results were compared with literature experimental or
      simulation data. Afterward, we attempted to model various thermodynamic
      properties of some binary systems composed of IL and organic solvent or water.
      The properties under study were the binary vapor-liquid, liquid-liquid, and solid
      liquid equilibria and the excess enthalpies of mixing. To calculate cross
      interaction energies we used the standard combining rules of Lorentz-Berthelot,
      Kleiner-Sadowski, and Wolbach-Sandler. It was shown that incorporation of
      temperature-dependent binary corrections was required to obtain much more
      accurate results than in the case of conventional predictions. Binary corrections
      were adjusted to infinite dilution activity coefficients of a particular solute
      in a given IL determined experimentally or predicted by means of the modified
      UNIFAC (Dortmund) group contribution method. We concluded that the latter method
      allows accurate and reliable calculations of bulk-phase properties in a totally
      predictive manner. 

PMID- 22469028
TI  - Synthesis of tertiary alkyl amines from terminal alkenes: copper-catalyzed
      amination of alkyl boranes.
AB  - A method for highly selective anti-Markovnikov hydroamination of terminal alkenes
      is reported. The one-pot procedure involves hydroboration of the alkene followed
      by a novel electrophilic amination of the alkyl borane catalyzed by an NHC-Cu
      complex. Terminal alkenes are successfully transformed into tertiary alkyl amines
      in the presence of a variety of functional groups in yields ranging from 80 to
      97% with excellent regioselectivity. Results of a preliminary study of the
      reaction mechanism are also described.

PMID- 22469029
TI  - Traumatic dental injuries in primary school children of South India--a report
      from district-wide oral health survey.
AB  - AIM: The aim of this study was to investigate the prevalence of dental trauma
      among primary school children aged 6-11 years in Belgaum, India. MATERIALS AND
      METHODS: A sample of 13,200 children from primary schools of Belgaum district was
      examined for dental trauma. WHO classification of dental trauma was used.
      RESULTS: Total number of children suffering from dental trauma was found to be
      1946 (14.74%). A significant gender influence on the occurrence of dental trauma
      was observed, with more boys (17.26%) experiencing dental trauma than girls
      (12.29%). More than 3 mm overjet and incompetent lips were also significantly
      associated with dental trauma in children. CONCLUSION: The findings of this study
      show that dental trauma has a moderately high prevalence among Indian primary
      school children. Community, especially parents and school teachers, should be
      educated about prevention and early management of dental trauma in children.

PMID- 22469030
TI  - Effective inactivation of food pathogens Listeria monocytogenes and Salmonella
      enterica by combined treatment of hypericin-based photosensitization and high
      power pulsed light.
AB  - AIMS: The aim of this study was to evaluate the inactivation efficiency of
      Listeria monocytogenes ATC(L3) C 7644 and Salmonella enterica serovar Typhimurium
      strain DS88 by combined treatment of hypericin (Hyp)-based photosensitization and
      high power pulsed light (HPPL). METHODS AND RESULTS: Cells were incubated with
      Hyp (1 * 10(-5) or 1 * 10(-7) mol l(-1)) in PBS and illuminated with a light
      lambda = 585 nm. For the combined treatment, bacteria were, after
      photosensitization, exposed to 350 pulses of HPPL (UV light dose = 0.023 J cm(
      2)). Fluorescence measurements were performed to evaluate optimal time for cell
      Hyp interaction. Results indicate that Hyp tends to bind both Listeria and
      Salmonella. After photosensitization treatment, Listeria population was reduced 7
      log, whereas Salmonella was inactivated just 1 log. Electron photomicrograps of
      Salmonella and Listeria confirmed that photosensitization induced total collapse
      of the Listeria cell wall, but not that of Salmonella. After combined
      photosensitization-HPPL treatment, the population of Listeria was diminished by 7
      log and Salmonella by 6.7 log. CONCLUSIONS: Listeria can be effectively
      inactivated by Hyp-based photosensitization (7 log), whereas Salmonella is more
      resistant to photosensitization and can be inactivated just by 1 log in vitro.
      Combined treatment of photosensitization and pulsed light inactivates effectively
      (6.7-7 log) both the Gram-positive and the more resistant to photosensitization
      Gram-negative bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: A new approach to
      combat Gram-positive and Gram-negative bacteria is proposed, combining
      photosensitization with high power pulsed light.

PMID- 22469031
TI  - Identification of intermediate in evolutionary model of enterohemorrhagic
      Escherichia coli O157.
AB  - Highly pathogenic enterohemorrhagic Escherichia coli (EHEC) O157 cause a spectrum
      of clinical signs that include diarrhea, bloody diarrhea, and hemolytic uremic
      syndrome. The current evolutionary model of EHEC O157:H7/H(-) consists of a
      stepwise evolution scenario proceeding from O55:H7 to a node (hypothetical
      intermediate) that then branches into sorbitol-fermenting (SF) O157:H(-) and non
      SF (NSF) O157:H7. To identify this hypothetical intermediate, we performed single
      nucleotide polymorphism analysis by sequencing of 92 randomly distributed
      backbone genomic regions of 40 O157:H7/H(-) isolates. Overall, 111 single
      nucleotide polymorphisms were identified in 75/92 partial open reading frames
      after sequencing 51,041 nt/strain. The EHEC O157:H7 strain LSU-61 from deer
      occupied an intermediate position between O55:H7 and both O157 branches (SF and
      NSF O157), complementing the stepwise evolutionary model of EHEC O157:H7/H(-).
      The animal origin of this intermediate emphasizes the value of nonhuman
      reservoirs in the clarification of the evolution of human pathogens.

PMID- 22469032
TI  - Sox2 targets cyclinE, p27 and survivin to regulate androgen-independent human
      prostate cancer cell proliferation and apoptosis.
AB  - OBJECTIVES: Sox2 is a major transcription factor and the transforming growth
      factor-alpha (TGF-alpha)/EGFR autocrine loop is a hallmark of prostate cancer
      progression. In this study, we have evaluated the effects and potential
      mechanisms of Sox2 on cell proliferation and apoptosis, and investigated effects
      of TGF-alpha on expression of Sox2 on androgen-independent human prostate cancer
      cells. MATERIALS AND METHODS: Expression of Sox2 has been determined by RT-PCR,
      western blot analysis and immunocytochemistry, using RNAi and over-expression
      strategy to study functions of Sox2 in DU145 and PC-3 cells. Changes in level of
      proliferation, cell cycle and apoptosis profiles were measured by MTT, colony
      forming, bromodeoxyuridine incorporation assays, cell cycle and annexin V
      analysis. RESULTS: Sox2 was expressed in six human prostate cancer cell lines,
      and its inhibition reduced cell proliferation and induced apoptosis in DU145
      cells. We have shown that knock-down of Sox2 inhibited G(1)  to S phase
      transition concomitantly with down-regulation of cyclin E and up-regulation of
      p27 proteins. Conversely, over-expression of Sox2 led to the opposite effect in
      PC-3 cells but its inhibition induced apoptosis by down-regulation of survivin in
      DU145 cells. We also found that TGF-alpha up-regulated Sox2 and survivin protein
      expression via the EGFR/PI3K/AKT pathway. CONCLUSIONS: Sox2 expression is
      necessary for cell proliferation and evasion of apoptosis in prostate cancer
      cells and TGF-alpha could regulate Sox2 and survivin expression by activating the
      EGFR/PI3K/AKT pathway.

PMID- 22469033
TI  - The pharmacokinetics of peginterferon alfa-2a and ribavirin in African American,
      Hispanic and Caucasian patients with chronic hepatitis C.
AB  - BACKGROUND: Amongst Caucasian, Hispanic and African Americans with genotype 1
      hepatitis C virus (HCV), there is a wide variation in response to treatment with
      peginterferon alfa-2a (PEG-IFN alfa-2a) and ribavirin. AIM: To evaluate the
      pharmacokinetics (PK) of PEG-IFN alfa-2a and ribavirin among these three groups.
      METHODS: Forty-seven patients with genotype 1 CHC (17 African Americans, 14
      Hispanics and 16 Caucasians) received 8 weeks of PEG-IFN alfa-2a (180 MUg/week)
      and ribavirin (1000 or 1200 mg/day). PEG-IFN alfa-2a serum concentrations and
      ribavirin plasma concentrations were measured following the first dose and at
      week 8. Pharmacokinetic parameters (C(max), T(max), AUC, CL/F) were estimated
      using noncompartmental methods. RESULTS: There was no difference in the
      pharmacokinetic parameters for PEG-IFN alfa-2a following single-dose or steady
      state administration between African American or Hispanic patients compared with
      Caucasian patients. Ribavirin pharmacokinetic parameters were similar between
      Hispanic and Caucasian patients for single-dose and steady-state administration.
      The single-dose C(max) was 33% lower (P < 0.05) in African American compared with
      Caucasian patients. Other ribavirin single-dose and steady-state pharmacokinetic
      parameters were slightly decreased (approximately 20% lower) in African American
      patients, but were not considered clinically meaningful. CONCLUSIONS: No
      differences were observed in PEG-IFN alfa-2a pharmacokinetic parameters between
      African American or Hispanic patients compared with Caucasian patients. For
      ribavirin, no differences were observed in pharmacokinetic parameters between
      Hispanic and Caucasian patients. While a trend towards increased ribavirin
      clearance and decreased exposure was observed in African American patients vs.
      Caucasian patients, the differences were small and not considered clinically
      meaningful (Clinical Trial Number: NP17354).

PMID- 22469034
TI  - Demonstration of non-specific colitis and increased crypt depth in colon of
      weaned pigs with diarrhea.

PMID- 22469035
TI  - What are the keys to successful thyroid FNA interpretation?
AB  - There is much concern expressed in the literature regarding the lack of
      predictive power of the thyroid fine needle aspiration/biopsy (TFNAB) approach to
      defining the nature of clinically detected thyroid nodules. This has been
      exacerbated in the past decade or more by the routine use of ultrasonography (US)
      in examining the thyroid as well as the introduction of molecular testing in the
      realm of thyroid pathology. Some have even gone so far as to suggest replacing
      the TFNAB with molecular signature testing to reduce the degree of uncertainty
      for a specific cytological diagnosis. This review addresses those concerns with a
      re-emphasis on understanding the basic keys to successfully evaluating a patient
      with a thyroid nodule by routine TFNAB examination. These keys include bringing
      to bear an experienced group of physicians in an integrated team approach, a
      sharpened focus on the TFNAB cytological categories and a grounded understanding
      of the predictive ability of molecular testing in a given patient when the
      cytological interpretation creates too much uncertainty in the minds of the
      patients and clinicians in attempting to reach a decision on how to manage a
      thyroid nodule. With this practical approach in mind, the false-negative and
      false-positive rates of "negative (benign)" and "positive (malignant)" thyroid
      aspirates should be no more than 1%; and the prevalence of an "indeterminate"
      aspirate - the area in TFNAB attracting the most attention for improvement with
      novel biomarkers - should be 10% or less. Thus, physicians should be capable of
      managing at least 90% of patients undergoing TFNAB in a confident manner without
      further testing beyond the routine, future re-examination of the patient's nodule
      to re-assess for any change in its nature or its impact on the patient's quality
      of life. The other 10% can then be considered for molecular testing in a manner
      tailored to those individuals truly in need of a more sophisticated - and
      expensive - approach to the characterization of their thyroid nodules. As the era
      of US has matured - just as with the era of serum PSA testing for prostate cancer
      in men - we have experienced a paradigm shift: Given the incidence of thyroid
      nodules in the U.S. adult population in comparison with the risk of dying of
      thyroid malignancy, the main role of TFNAB is to reduce the need for surgical
      intervention.

PMID- 22469036
TI  - Comparative pathology of the natural infections by Mycobacterium bovis and by
      Mycobacterium caprae in wild boar (Sus scrofa).
AB  - The potential role of wild animals in the maintenance and spread of tuberculosis
      (TB) infection in domestic livestock is of particular importance in countries
      where eradication programs have substantially reduced the incidence of bovine
      tuberculosis but sporadic outbreaks still occur. Mycobacterium bovis is the agent
      mainly isolated in wildlife in Spain, but recently, infections by Mycobacterium
      caprae have increased substantially. In this study, we have analysed 43
      mandibular lymph nodes samples containing TB-like lesions from 43 hunted wild
      boar from Madrid and Extremadura (central and south-western regions of Spain).
      After isolation, identification and typing of Mycobacterium tuberculosis complex
      isolates, we found that 23 mandibular lymph nodes involved M. caprae infections
      and 20 M. bovis. The lesions were compared for histopathology (different
      granuloma stage and number of multinucleated giant cells (MNGCs)), and acid-fast
      bacilli (AFBs) were quantified in the Ziehl-Neelsen-stained slides. Granulomas
      produced by M. caprae showed more stage IV granulomas, more MNGCs and higher AFBs
      counts than those induced by M. bovis. In conclusion, lesions caused by M. caprae
      would be more prone to the excretion of bacilli, and infected animals result as a
      high-risk source of infection for other animals.

PMID- 22469037
TI  - Acetylcholine chloride: physical profile.

PMID- 22469038
TI  - Acetylcholine chloride: analytical profile.

PMID- 22469039
TI  - Benazepril hydrochloride: comprehensive profile.

PMID- 22469040
TI  - Ciprofloxacin: physical profile.

PMID- 22469041
TI  - Ciprofloxacin: analytical profile.

PMID- 22469042
TI  - Ciprofloxacin: drug metabolism and pharmacokinetic profile.

PMID- 22469043
TI  - Dipyridamole: comprehensive profile.

PMID- 22469044
TI  - Mefenamic Acid: analytical profile.

PMID- 22469045
TI  - Nimodipine: physical profile.

PMID- 22469047
TI  - Nimodipine: drug metabolism and pharmacokinetic profile.

PMID- 22469046
TI  - Nimodipine: analytical profile.

PMID- 22469048
TI  - Cumulative index.

PMID- 22469051
TI  - Preface.

PMID- 22469049
TI  - Affiliations of editor and contributors.

PMID- 22469052
TI  - Modulation of gene expression during early stages of reconnection of the turtle
      spinal cord.
AB  - The spinal cord of the freshwater turtle Trachemys dorbignyi regenerates after
      complete transection (Rehermann et al. J. Comp. Neurol. 515, 2009, 197-214). This
      remarkable ability may be related to the persistence around the central canal
      (CC) of progenitors functionally clustered via connexin 43 (Cx43) that express
      brain lipid binding protein (BLBP) and the transcription factor Pax6 (Russo et
      al. J. Neurosci. 28, 2008, 8510-8516). Indeed, because BLBP+ cells appear in the
      bridge joining the rostral and caudal stumps, we speculated that progenitors
      contacting the central canal may play a key part in spinal cord regeneration. To
      test this hypothesis, we designed degenerated primers pairing conserved regions
      for key proteins synthesized in progenitors (BLBP, Cx43, and Pax6) and the
      neuronal protein HuB. Fragments of these proteins were amplified, cloned, and
      sequenced. Based on these sequences, we analyzed the changes in the expression
      levels using quantitative real-time RT-PCR with specific primers, comparing the
      injured spinal cord at different times after injury (4, 12, 20, and 60 days) with
      uninjured spinal cords. We found a transient, early increase of BLBP, Cx43 and
      HuB mRNA, with Pax6 remaining unchanged. These results suggest that the selected
      genes--active in progenitor cells--play an important part in early mechanisms of
      spinal cord regeneration.

PMID- 22469053
TI  - Characterization of Mycobacterium orygis as M. tuberculosis complex subspecies.
AB  - The oryx bacilli are Mycobacterium tuberculosis complex organisms for which
      phylogenetic position and host range are unsettled. We characterized 22 isolates
      by molecular methods and propose elevation to subspecies status as M. orygis. M.
      orygis is a causative agent of tuberculosis in animals and humans from Africa and
      South Asia.

PMID- 22469054
TI  - Neurophysiological biomarkers support bipolar-spectrum disorders within psychosis
      cluster.
AB  - BACKGROUND: Mismatch negativity (MMN) and P3a are event-related potentials that
      index deviance detection and the orienting response, respectively. We have
      previously shown that the MMN/P3a complex is impaired in patients with
      schizophrenia and affective spectrum psychoses, which suggests that it may index
      a common pathophysiology and argues against the purported specificity in
      schizophrenia. Further research is warranted to determine whether patients with
      bipolar-spectrum disorders show similar impairments in these biomarkers. METHODS:
      We assessed patients aged 15-30 years with early schizophrenia-spectrum disorders
      (schizophrenia, schizoaffective disorder, schizophreniform disorder), early
      bipolar-spectrum disorders (bipolar I or II, with and without psychotic features)
      and healthy, matched controls. We acquired MMN/P3a amplitudes during a 2-tone,
      auditory paradigm with 8% duration deviants. Clinical, psychosocial and neuro
      psychological assessments were also undertaken. RESULTS: We included 20 patients
      with schizophrenia-spectrum disorders, 20 with bipolar-spectrum disorders and 20
      controls in our study. Both patient groups showed significantly reduced
      frontocentral MMN and central P3a amplitudes. The schizophrenia-spectrum group
      had additional impairments in left temporal MMN and frontal P3a. Both patient
      groups performed worse than controls across psychosocial and clinical measures;
      however, only the schizophrenia-spectrum group performed significantly worse than
      controls for cognitive measures. Correlational analyses between patient groups
      revealed associations between frontocentral or left temporal MMN and psychiatric
      symptomatology or quality of life measures. LIMITATIONS: Limitations to our study
      include the modest sample size and the lack of control with regards to the
      effects of other (i.e., nonantipsychotic) psychotropic medications. CONCLUSION:
      Compared with patients in early stages of schizophrenia-spectrum disorders, those
      in the early stages of bipolar-spectrum disorders are similarly impaired in
      established biomarkers for schizophrenia. These findings support a shared
      diathesis model for psychotic and bipolar disorders. Furthermore, MMN/P3a may be
      a biomarker for a broader pathophysiology that overlaps traditional diagnostic
      clusters.

PMID- 22469056
TI  - Exercise stress testing is the most commonly performed exercise for determining
      the presence of myocardial ischemia. Foreword.

PMID- 22469055
TI  - Ionotropic glutamate receptor mRNA editing in the prefrontal cortex: no
      alterations in schizophrenia or bipolar disorder.
AB  - BACKGROUND: Dysfunction of glutamate neurotransmission has been implicated in the
      pathology of schizophrenia and bipolar disorder, and one mechanism by which
      glutamate signalling can be altered is through RNA editing of ionotropic
      glutamate receptors (iGluRs). The objectives of the present study were to
      evaluate the editing status of iGluRs in the human prefrontal cortex, determine
      whether iGluR editing is associated with psychiatric disease or suicide and
      evaluate a potential association between editing and alternative splicing in the
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) iGluR subunits' pre
      mRNA. METHODS: We studied specimens derived from patients with antemortem
      diagnoses of bipolar disorder (n = 31) or schizophrenia (n = 34) who died by
      suicide or other causes, and from psychiatrically healthy controls (n = 34) who
      died from causes other than suicide. The RNA editing at all 8 editing sites
      within AMPA (GluA2-4 subunits) and kainate (GluK1-2 subunits) iGluRs was analyzed
      using a novel real-time quantitative polymerase chain reaction assay. RESULTS: No
      differences in editing were detected among schizophrenia, bipolar or control
      groups or between suicide completers and patients who died from causes other than
      suicide. The editing efficiency was significantly higher in the flop than in the
      flip splicoforms of GluA3-4 AMPA subunits (all p < 0.001). LIMITATIONS: The study
      is limited by the near absence of specimens from medicationnaive psychiatric
      patients and considerable variation in medication regimens among individuals,
      both of which introduce considerable uncertainty into the analysis of potential
      medication effects. CONCLUSION: We found that iGluR RNA editing status was not
      associated with bipolar disorder, schizophrenia or suicide. Differences in
      editing between flip and flop splicoforms suggest that glutamate sensitivity of
      receptors containing GluA3 and/or GluA4 flop subunits is moderated as a result of
      increased editing.

PMID- 22469057
TI  - An update on exercise stress testing.
AB  - Exercise stress testing is the most commonly used noninvasive method to evaluate
      for coronary artery disease in men and women. Although emphasis has been placed
      on the diagnostic value of ST-segment depression, the exercise stress test
      provides other valuable diagnostic and prognostic data, beyond ST-segment
      depression. The value of these variables, which include exercise capacity,
      chronotropic response, heart rate recovery, blood pressure response, and the Duke
      Treadmill Score, are reviewed in this article. In addition, the gender
      differences seen with these exercise testing variables are reviewed. In this
      modern era of exercise stress testing, making use of all the information from a
      stress test and creating a comprehensive stress testing report are recommended in
      the evaluation of patients with suspected coronary artery disease who undergo
      exercise stress testing.

PMID- 22469058
TI  - Age, marital status and changes in dietary habits in later life: a 21-year follow
      up among Finnish women.
AB  - OBJECTIVE: To examine 21-year longitudinal changes in dietary habits and their
      associations with age and marital status among women aged 50-60 years at
      baseline. DESIGN: Prospective, longitudinal study of a cohort in the FINMONICA
      population-based risk factor survey with clinical assessments in 1982, 1992 and
      2003. Dietary habits were assessed via self-reported consumption of foods
      typically contributing to SFA, cholesterol and sugar intakes in the Finnish diet.
      A dietary risk score based upon five items was used. SETTING: Kuopio region,
      Finland. SUBJECTS: Complete data from all three assessments for 103 women of the
      original cohort of 299 were included for two age groups: 50-54 and 55-60 years at
      baseline. RESULTS: Dietary habits improved between 1982 and 1992 and showed
      continued but less pronounced improvement between 1992 and 2003: within the
      younger age group, 78 % of the women reduced the number of dietary risk points
      from the 1982 to 2003 scores, whereas 3 % increased them and 19 % reported no
      change. In the older age group these percentages were 61 %, 23 % and 16 %,
      respectively. Women who remained married showed a steadier decline in dietary
      risk points than single women or women who were widows at the beginning of the
      follow-up. CONCLUSIONS: Older women make positive changes to their dietary habits
      but the consistency of these changes may be affected by the ageing process,
      marital status and changes in the latter.

PMID- 22469059
TI  - Deficient reporting in avian influenza surveillance, Mali.

PMID- 22469060
TI  - Polymer-based restoration of left ventricular mechanics.
AB  - Heart failure continues to be a major health care concern with relatively few
      options for severely advanced heart failure patients. The hallmark of heart
      failure is the progressive dilatation of the left ventricle, thinning of the left
      ventricular wall leading to increased wall stress and increased myocardial oxygen
      consumption. Applying Laplace's law to the failing dilated ventricle, left
      ventricular augmentation utilizes a tissue engineering strategy to increase wall
      thickness and reduce chamber diameter, resulting in a decrease in wall stress and
      improved left ventricular function. A review of the rationale for an in situ
      tissue engineering approach for this treatment of heart failure and early
      clinical results of the Algisyl-LVRTM program are presented.

PMID- 22469061
TI  - Decreased bone density and bone strength in a mouse model of severe factor VIII
      deficiency.

PMID- 22469062
TI  - Interaction of a 17q12 variant with both fetal and infant smoke exposure in the
      development of childhood asthma-like symptoms.
AB  - BACKGROUND: Gene variants on chromosome 17q12-21 are associated with an increased
      risk of childhood-onset asthma, a risk known to be modified by environmental
      tobacco smoke (ETS). OBJECTIVES: To assess whether the association of rs2305480
      on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4
      years of life is modified by smoke exposure during fetal and early postnatal
      life. METHODS: We used data from two independent prospective cohort studies from
      fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed
      maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like
      symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal
      cough, were reported by parents when the children were 1, 2, 3, and 4 years.
      Analyses were based on a total group of 4461 Caucasian children. RESULTS: The G
      risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds
      ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like
      symptoms was stronger among children who were exposed to smoke during fetal life
      (P-interaction = 0.04). Smoke exposure in early postnatal life was also
      associated with an increased effect of the 17q12 single nucleotide polymorphism
      (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were
      consistent in both cohorts. CONCLUSION: A 17q12 variant, rs2305480, was
      associated with asthma-like symptoms in preschool children, and this association
      was modified by smoke exposure already during fetal life, and in infancy. Further
      investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation
      to pathophysiological pathways is needed.

PMID- 22469063
TI  - A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth
      and promotes neuronal survival.
AB  - Apart from its hematopoietic activity, erythropoietin (EPO) is also known as a
      tissue-protective cytokine. In the brain, EPO and its receptor are up-regulated
      in response to insult and exert pro-survival effects. EPO binds to its receptor
      (EPOR) via high- and low-affinity binding sites (Sites 1 and 2, respectively),
      inducing conformational changes in the receptor, followed by the activation of
      downstream signaling cascades. Based on the crystal structure of the EPO:EPOR(2)
      complex, we designed a peptide, termed Epobis, whose sequence encompassed amino
      acids from binding Site 1. The present study shows that the Epobis peptide
      specifically binds to EPOR and induces neurite outgrowth from primary neurons in
      an EPOR-expression dependent manner. Furthermore, Epobis promoted the survival of
      hippocampal and cerebellar neuronal cultures after kainate treatment and KCl
      deprivation, respectively. Thus, we identified a new functional agonist of EPOR
      with the potential to promote neuroregeneration and neuroprotection.

PMID- 22469064
TI  - Protein and water dynamics in bovine serum albumin-water mixtures over wide
      ranges of composition.
AB  - Dielectric dynamic behavior of bovine serum albumin (BSA)-water mixtures over
      wide ranges of water fractions, from dry protein until 40 wt % in water, was
      studied through dielectric relaxation spectroscopy (DRS). The alpha relaxation
      associated with the glass transition of the hydrated system was identified. The
      evolution of the low temperature dielectric relaxation of small polar groups of
      the protein surface with hydration level results in the enhancement of dielectric
      response and the decrease of relaxation times, until a critical water fraction,
      which corresponds to the percolation threshold for protonic conductivity. For
      water fractions higher than the critical one, the position of the secondary nu
      relaxation of water saturates in the Arrhenius diagram, while contributions
      originating from water molecules in excess (uncrystallized water or ice) follow
      separate relaxation modes slower than the nu relaxation.

PMID- 22469065
TI  - Prediction of recurrence of hypertensive disorders of pregnancy between 34 and 37
      weeks of gestation: a retrospective cohort study.
AB  - OBJECTIVE: To assess the recurrence risk of late-preterm hypertensive disease of
      pregnancy, and to determine whether potential risk factors are predictive.
      DESIGN: Retrospective cohort study. SETTING: Three secondary and three tertiary
      care hospitals in the Netherlands. POPULATION: We identified women with a
      hypertensive disorder in the index pregnancy and delivery at 34-37 weeks of
      gestation, between January 2000 and December 2002. METHODS: Data were extracted
      from medical files and women were approached for additional information on
      subsequent pregnancies. An adverse outcome was defined as the recurrence of a
      hypertensive disorder in the next subsequent pregnancy. MAIN OUTCOME MEASURES:
      Absolute risk of recurrence and a prediction model containing demographic and
      clinical factors predictive for adverse outcome. RESULTS: We identified 425 women
      who matched the criteria, of whom 351 could be contacted. Of these women, 189
      (54%) had had a subsequent pregnancy. Hypertensive disorders recurred in 96 (51%,
      95% CI 43-58%) women, of whom 17 (9%, 95% CI 5-14%) delivered again before 37
      weeks of gestation. Chronic hypertension and maternal age were the strongest
      predictors for recurrence. Women undergoing recurrence had a nine-fold chance of
      developing chronic hypertension (37% versus 6%, OR 8.7, 95% CI 3.3-23).
      CONCLUSIONS: Women with hypertensive disorders and late-preterm delivery have a
      50% chance of recurrence, but only a 9% chance of recurrence resulting in
      delivery before 37 weeks of gestation. Women with chronic hypertension are prone
      to develop recurrence, and women with a recurrence more often developed chronic
      hypertension.

PMID- 22469066
TI  - Letter to the editor: "Review of the epidemiologic literature on residential
      exposure to perchloroethylene" by John A. Bukowski.

PMID- 22469068
TI  - Protective role of chrysin against oxidative stress in d-galactose-induced aging
      in an experimental rat model.
AB  - AIM: To evaluate the putative protective role of chrysin, an isoflavone, on D
      galactose-induced aging in an experimental rat model. METHODS: Rats were divided
      into five groups of five each. Group I received 0.9% saline only. Groups II, III
      and IV received d-galactose (50 mg/kg bodyweight) intraperitoneally, additionally
      group III and group IV received chrysin (20 mg/kg bodyweight) and alpha
      tocopherol acetate (200 mg/kg bodyweight), respectively. Group V received chrysin
      alone. The experiment period was for a period of 8 weeks. After the rats were
      killed, the tissue samples were analyzed for mean activities of superoxide
      dismutase, catalase, glutathione peroxidase, glutathione-S-transferase,
      glutathione reductase, glucose-6-phosphate dehydrogenase, reduced glutathione,
      vitamin C, vitamin E, malondialdehyde and protein carbonyl. Histopathological
      studies were also carried out for morphological conformation. RESULTS: Tissue
      samples from D-galactose-exposed untreated rats showed significantly (P < 0.05)
      lower levels of enzymatic and non-enzymatic anti-oxidants, and significantly (P <
      0.05) higher levels of malondialdehyde and protein carbonyl when compared with
      group I and group III rats. Oral administration of chrysin for a period of 8
      weeks, concomitant with the exposure to D-galactose, appeared to protect against
      oxidative damage and maintained all parameters at near normal levels.
      Histopathological studies confirmed the oxidative damage caused by D-galactose
      alone in tissues and also showed the tissue protective role of chrysin in rats
      receiving D-galactose and chrysin. CONCLUSION: These results suggest that chrysin
      protects against oxidative stress-induced tissue damage in D-galactose-induced
      aging in an experimental rat model.

PMID- 22469069
TI  - Interaction of chitosan and mucin in a biomembrane model environment.
AB  - Chitosans have been widely exploited in biological applications, including drug
      delivery and tissue engineering, especially owing to their mucoadhesive
      properties, but the molecular-level mechanisms for the chitosan action are not
      known in detail. It is believed that chitosan could affect the mucus by
      interacting with the proteins mucins, in a process mediated by the cell membrane.
      In this study we used Langmuir monolayers of dimyristoylphosphatidic acid (DMPA)
      as simplified membrane models to investigate the interplay between the activity
      of mucins and chitosan. Surface pressure and surface potential measurements were
      performed with DMPA monolayers onto which chitosan and/or mucin was adsorbed. We
      found that the expanding effect from mucin was considerably reduced when chitosan
      was injected after mucin had been adsorbed on the DMPA monolayer. The results
      were consistent with the formation of complexes between mucin and chitosan, thus
      highlighting the importance of electrostatic interactions. Furthermore, chitosan
      could remove mucin that was co-deposited along with DMPA in Langmuir-Blodgett
      (LB) films, which could be ascribed to molecular-level interactions between
      chitosan and mucin inferred from the FTIR spectra of the LB films. In conclusion,
      the results with Langmuir and LB films suggest that electrostatic interactions
      are crucial for the mucoadhesive mechanism, which is affected by the complexation
      between chitosan and mucin.

PMID- 22469070
TI  - Cosavirus infection in persons with and without gastroenteritis, Brazil.
AB  - To determine possible cosavirus association with clinical disease, we used real
      time reverse transcription PCR to test children and HIV-positive adults in Brazil
      with and without gastroenteritis. Thirteen (3.6%) of 359 children with
      gastroenteritis tested positive, as did 69 (33.8%) of 204 controls. Low
      prevalence, frequent viral co-infections, and low fecal cosavirus RNA
      concentrations argue against human pathogenicity.

PMID- 22469071
TI  - Review article: fructose in non-alcoholic fatty liver disease.
AB  - BACKGROUND: The role of excess fructose intake in the pathogenesis of non
      alcoholic fatty liver disease (NAFLD) has recently received increasing attention,
      but the pathophysiology of this relationship has been only partly elucidated.
      AIM: To provide an overview of the potential role played by fructose in the
      pathogenesis of NAFLD by focusing on both indirect and direct harmful effects.
      METHODS: Experimental and clinical studies which investigated the relation of
      fructose with NAFLD are reviewed. RESULTS: Several factors may potentially
      contribute to fructose-induced NAFLD, including the induction of the metabolic
      syndrome, copper deficiency, bacterial translocation from the gut to the liver,
      the formation of advanced glycation endproducts and a direct dysmetabolic effect
      on liver enzymes. CONCLUSIONS: Experimentally-increased fructose intake
      recapitulates many of the pathophysiological characteristics of the metabolic
      syndrome in humans, which may in turn lead to NAFLD. However, the majority of
      experimental studies tend to involve feeding excessively high levels of fructose
      (60-70% of total energy intake) which is not reflective of average human intake.
      Hopefully, the combination of in vivo, in vitro and genetic research will provide
      substantial mechanistic evidence into the role of fructose in NAFLD development
      and its complications.

PMID- 22469072
TI  - Assessment of nitric oxide, advanced oxidation protein products, malondialdehyde,
      and thiol levels in patients with restless legs syndrome.
AB  - OBJECTIVES: We aimed to determine the importance of oxidative stress in the
      pathogenesis of restless legs syndrome (RLS) by quantification of advanced
      oxidation protein products and total thiol levels (as markers of oxidative
      protein damage), nitric oxide levels (as an antioxidant and endothelial
      function), and malondialdehyde levels (as a marker of lipid peroxidation) in
      patients with RLS. DESIGN AND METHODS: A total of 22 patients with primary RLS
      were enrolled in the study and 20 age-and-gender-matched healthy subjects were
      enrolled as a control group. Serum nitric oxide, malondialdehyde, thiol levels,
      and plasma advanced oxidation protein products levels were determined by
      spectrophotometric methods. RESULTS: Serum nitric oxide and thiol levels were
      lower in the patient group than in controls (p = 0.007 and p = 0.017,
      respectively). Plasma advanced oxidation protein products levels and serum
      malondialdehyde levels were found to be higher in patients with RLS than in
      controls (p = 0.017 and p = 0.008, respectively). Serum malondialdehyde level was
      found to be positively correlated with plasma advanced oxidation protein products
      levels (p = 0.039). Serum thiol level was found to be negatively correlated with
      plasma advanced oxidation protein products levels (p = 0.030). CONCLUSIONS:
      Increased advanced oxidation protein products, malondialdehyde levels, and
      decreased thiol and nitric oxide levels, may suggest that patients with RLS are
      under oxidative stress. Although both lipid peroxidation and protein oxidation
      may have a role in atherosclerosis in RLS, those factors may be related to the
      pathogenesis of RLS.

PMID- 22469073
TI  - Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolaemia:
      a systematic review and economic evaluation.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic
      condition causing a high risk of coronary heart disease. The prevalence of this
      disease is about 1 in 500 in the UK, affecting about 120,000 people across the
      whole of the UK. Current guidelines recommend DNA testing, however, these
      guidelines are poorly implemented, therefore 102,000 or 85% of this group remain
      undiagnosed. OBJECTIVES: To assess the diagnostic accuracy, effect on patient
      outcomes and cost-effectiveness of Elucigene FH20 and LIPOchip for the diagnosis
      of FH. DATA SOURCES: Electronic databases including MEDLINE, MEDLINE In-Process &
      Other Non-Indexed Citations, EMBASE, BIOSIS, Science Citation Index, Conference
      Proceedings Citation Index - Science and Cochrane Controlled Trials Register were
      searched until January 2011. REVIEW METHODS: A systematic review of the
      literature on diagnostic accuracy was carried out according to standard methods.
      An economic model was constructed to assess the cost-effectiveness of alternative
      diagnostic strategies for the confirmation of clinically diagnosed FH in index
      cases and for the identification and subsequent testing of first-, second- and
      possibly third-degree biological relatives of the index case. Twelve strategies
      were evaluated linking diagnostic accuracy to treatment outcomes and hence
      quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity
      analyses were undertaken to investigate model and parameter uncertainty. RESULTS:
      Fifteen studies were included for diagnostic accuracy; three reported Elucigene
      FH20, five reported LIPOchip, four reported low-density lipoprotein cholesterol
      (LDL-C) tests and three reported an age- and gender-specific LDL-C test against a
      reference standard of comprehensive genetic analysis (CGA). Sensitivity ranged
      from 44% to 52% for Elucigene FH20 and from 33.3% to 94.5% for various versions
      of LIPOchip in detecting FH-causing mutations in patients with a clinical
      diagnosis of FH. For LIPOchip version 10 (designed to detect 189 UK specific
      mutations), sensitivity would be 78.5% (based on single-centre data - Progenika,
      personal communication). For all other Elucigene FH20 or LIPOchip studies (apart
      from one LIPOchip study), specificity could not be calculated as no false
      positive results could be derived from the given data. The LDL-C test was
      generally reported to be highly sensitive but with low specificity. For age- and
      gender-specific LDL-C cut-offs for cascade testing, sensitivity ranged from 68%
      to 96%. One UK-based study reported sensitivity of 91% and specificity of 93%.
      For the cost-effectiveness review, only one study reporting cost-effectiveness of
      any one of the comparators for this assessment was identified. Pre-screen
      strategies such as Elucigene FH20 followed by CGA were not cost-effective and
      were dominated by the single more comprehensive tests (e.g. CGA). Of the non
      dominated strategies, Elucigene FH20, LIPOchip platform (Spain) and CGA were all
      cost-effective with associated incremental cost-effectiveness ratios (ICERs)
      relative to LDL-C of dominance (test is less costly and more effective), L871 and
      L1030 per QALY gained respectively. CGA generates the greatest QALY gain and,
      although other tests have lower ICERs relative to LDL-C, this is at the expense
      of QALY loss compared with the CGA test. Probabilistic sensitivity analysis shows
      that CGA is associated with an almost 100% probability of cost-effectiveness at
      the conventional value of willingness to pay of L20,000 per QALY gain.
      LIMITATIONS: There was much uncertainty regarding the diagnostic accuracy of the
      included tests, with wide variation in sensitivity across reported studies. A
      lack of published information for the most recent version of LIPOchip created
      additional uncertainty, especially in relation to the chip's ability to detect
      copy number changes. For the economic modelling, we aimed to choose the best
      studies for the base-case sensitivity of the tests; however, a number of informed
      choices based on clinical expert opinion had to be made in the absence of
      published studies for a number of other parameters in the modelling. This adds
      some uncertainty to our results, although it is unlikely that these would be
      sufficient in magnitude to alter our main results and conclusions. CONCLUSIONS:
      As targeted tests designed to detect a limited number of genetic mutations,
      Elucigene FH20 and LIPOchip cannot detect all cases of FH, in contrast with CGA.
      CGA is therefore the most effective test in terms of sensitivity and QALY gain,
      and is also highly cost-effective with an associated ICER of L1030 per QALY gain
      relative to current practice (LDL-C). Other tests such as Elucigene FH20 and
      LIPOchip are also cost-effective; however, because of inferior sensitivity
      compared with CGA, these tests offer cost savings but at the expense of large
      QALY losses compared with CGA. Further prospective multicentred studies are
      required to evaluate the diagnostic accuracy of new and emerging tests for FH
      with the LDL-C test in patients with a clinical diagnosis based on the Simon
      Broome criteria. Such studies should verify both test-positive and -negative
      results against a reference standard of CGA and should include a full economic
      evaluation. FUNDING: The National Institute for Health Research Health Technology
      Assessment programme.

PMID- 22469074
TI  - Recruiting patients and collecting data for an observational study using
      computerised record pop-up prompts: the PROG-RES study.
AB  - BACKGROUND AND AIM: Engagement of general practitioners (GPs) and recruitment of
      patients are ever present problems in primary care studies. This paper seeks to
      demonstrate that electronic prompts represent one method of easing the burden on
      GPs to recruit individual patients to studies and also provide the opportunity to
      collect research data during a normal consultation. METHODS: Older adults
      consulting for non-inflammatory musculoskeletal pain from five general practices
      in Cheshire were recruited to a prospective cohort study (the PROG-RES study).
      Recruitment of patients was aided by a computer prompt during relevant
      consultations. When triggered by an appropriate Read code, a pop-up template
      appeared on the consultation screen prompting the GPs to record the answers to
      seven brief questions. A self-complete questionnaire was mailed to patients who
      had completed templates by the Keele GP Research Network team and permission was
      sought to access their medical records. A feasibility study suggested that the
      potential number of activated templates in the practice within four months would
      be 636. RESULTS: The 44 GPs completed 650 electronic templates during the four
      month recruitment period. Almost 40% of recruitment was within four weeks and
      greater than 95% of recruitment was within 16 weeks. Practices A-D completed
      electronic templates at a similar rate (1.61-1.86 templates per 1000 patients),
      although practice E completed templates at a lower frequency (0.76) due to
      internal difficulties. Completion of individual items ranged from 98% to 83% and
      completion of all seven questions was recorded in 63% of patients; 4% of patients
      had three or fewer responses recorded. Conclusion Templates activated by
      appropriate codes in the GP consultation can facilitate recruitment to
      observational studies in primary care. It is possible to collect high-quality
      research data within a normal consultation. This may be a model for use in future
      studies in primary care.

PMID- 22469075
TI  - Long-term outcomes of short dental implants supporting single crowns in posterior
      region: a clinical retrospective study of 5-10 years.
AB  - OBJECTIVE: Aimed to evaluate the long-term clinical and radiographic outcomes of
      short implants supporting single crowns in the posterior regions. MATERIAL AND
      METHODS: A retrospective study design was adopted. The clinical and radiographic
      data of 231 short implants (intra-bony length <=8 mm) supporting single crowns in
      168 patients, were collected after 5-10 (mean 7.22) years' follow-up. Implant and
      prosthesis failures, peri-implant marginal bone loss, biological and technical
      complications were evaluated. The influence factors on implant failure were
      studied. RESULTS: In total 4 implants and 11 prostheses failed. The 10-year (5
      year) cumulative survival rate was 98.3% (98.7%) for implant-based analysis and
      97.6% (98.2%) for patient-based analysis. The short implants placed in type IV
      bone yielded more failures than in type I-III and presented a survival rate of
      94.0%. The 10-year survival rate of the prostheses was 95.2%. The mean marginal
      bone loss between implant installation and the 10 years' follow-up visit was 0.63
      +/- 0.68 mm. The marginal bone loss between the first and 5th year was minimal
      (0.05 +/- 0.10mm and not statistically significant). 18 (7.8%) implants were
      exposed to biological complications, whereas 29 (12.6%) implants were involved in
      technical complications. CONCLUSIONS: High survival rates for both the implants
      and the prostheses could be achieved after 5-10 years for short implants
      supporting single crowns, without severe marginal bone loss and complications.
      One may conclude that a single crown supported by a short implant is a
      predictable treatment modality. However, short implants in type IV bone sites
      should be applied with caution.

PMID- 22469076
TI  - Emergence of unusual G6P[6] rotaviruses in children, Burkina Faso, 2009-2010.
AB  - To obtain more information about rotavirus (ROTAV) genotypes in Burkina Faso, we
      characterized 100 ROTAVs isolated from fecal samples of children with acute
      gastroenteritis in the capital city of Ouagadougou, during December 2009-March
      2010. Of note, 13% of the ROTAV-positive samples, including those with mixed
      infections, were positive for the unusual G6 genotype ROTAV strain. The genotypes
      identified were G9P[8], G6P[6], G1P[6], G3P[6], G1P[8], and G2P[4]. G9P[8]
      subgroup (SG)II strains dominated during the beginning of the ROTAV season, but
      later in the season, other G types associated with P[6] and SGI specificity
      emerged. This emergence was related to a shift in the overall age of infected
      children; ROTAV SGII infected younger children and induced more severe symptoms.
      The finding of a high incidence of G6P[6] strains highlights the need for long
      term surveillance of ROTAV strains in Burkina Faso, especially when ROTAV
      vaccination is being considered in several African countries.

PMID- 22469077
TI  - Evaluation of phototoxic potential of aerial components of the fig tree against
      human melanoma.
AB  - OBJECTIVES: To date, Ficus carica L. cultivar Dottato (F. carica) has not been
      studied from a phototoxic point of view. In the present work, aerial components
      of F. carica from Italy, were examined to assess their antioxidant and phototoxic
      activity on human melanoma cells. A relationship between antioxidant, phototoxic
      activities and chemical composition has also been investigated. MATERIALS AND
      METHODS: Coumarin and fatty acid content in F. carica leaves, bark and woody
      parts were examined and compared by capillary GC and GC/MS. Polyphenolic content
      was also determined. Linoleic acid peroxidation and DPPH test were used to assess
      antioxidant activities, and MTT assay was used to evaluate anti-proliferative
      activity, on C32 human melanoma cells, after irradiation with a UVA dose of 1.08
      J/cm(2). RESULTS: Leaves demonstrated the best antioxidant and anti-proliferative
      activity in comparison to bark and wood. In particular, leaves were shown to
      possess the highest anti-radical activity and inhibition of peroxidation, with
      IC(50) values of 64 and 1.48 MUg/ml respectively. The leaves had highest anti
      proliferative activity with IC(50) value of 3.92 MUg/ml. The phytochemical
      investigation revealed different composition between the coumarins, psoralen and
      bergapten, fatty acids, polyphenols and flavonoid content among plant parts.
      CONCLUSIONS: Data obtained indicate that this type of fig tree may constitute an
      excellent source of bioactive compounds, such as phenolics, coumarins and fatty
      acids. This study offers a new perspective in developing others formulations
      potentially useful in photodynamic therapy for treatment of non-melanoma skin
      cancers.

PMID- 22469078
TI  - Identification of potential risk factors associated with highly pathogenic avian
      influenza subtype H5N1 outbreak occurrence in Lagos and Kano States, Nigeria,
      during the 2006-2007 epidemics.
AB  - Highly pathogenic avian influenza HPAI H5N1 was first reported in Africa in 2006,
      in Nigeria. The country experienced severe outbreaks in 2006 and 2007, strongly
      affecting the poultry population. Current knowledge on potential risk factors for
      HPAI H5N1 occurrence in poultry farms in Nigeria is limited. Therefore, we
      conducted a case-control study to identify potential farm-level risk factors for
      HPAI H5N1 occurrence in two areas of the country that were affected by the
      disease in 2006 and 2007, namely the States of Lagos and Kano. A case-control
      study was conducted at the farm level. A convenience sample of 110 farms was
      surveyed. Data on farm characteristics, farm management and trade practices were
      collected. Logistic regression was used to identify factors associated with farms
      that confirmed positive for HPAI. Having a neighbouring poultry farm was
      identified as a potential risk factor for disease occurrence [OR, 5.23; 95% CI,
      (0.88-30.97); P-value = 0.048]. Farm staff washing their hands before handling
      birds was a protective factor [OR, 0.14; 95% CI, (0.05-0.37); P-value <0.001], as
      well as not allowing traders to enter the farm [OR, 0.23; 95% CI, (0.08-0.70); P
      value = 0.008]. Our study highlighted the importance of trade and proximity
      between poultry farms in the epidemiology of HPAI H5N1 and the role of
      biosecurity in disease prevention in Kano and Lagos States. Despite the
      limitations owing to the sampling strategy, these results are consistent with
      other risk factor studies previously conducted on HPAI H5N1 in both Africa and
      other regions, suggesting similar risk factor patterns for HPAI H5N1 virus spread
      and substantiating current knowledge regarding the epidemiology of the disease.
      Finally, this study generated information from areas where data are difficult to
      obtain.

PMID- 22469079
TI  - Myxozoan parasite in brain of critically endangered frog.

PMID- 22469080
TI  - Langerhans cells and T cells sense cell dysplasia in oral leukoplakias and oral
      squamous cell carcinomas--evidence for immunosurveillance.
AB  - Leukoplakias (LPLs) are lesions in the oral mucosa that may develop into oral
      squamous cell carcinoma (OSCC). The objective of this study was to assess
      presence and distribution of dendritic Langerhans cells (LCs) and T cells in
      patients with LPLs with or without cell dysplasia and in oral squamous cell
      carcinoma (OSCC). Biopsy specimens from patients with leukoplakias (LPLs) with or
      without dysplasia and oral squamous cell carcinoma (OSCC) were immunostained with
      antibodies against CD1a, Langerin, CD3, CD4, CD8 and Ki67, followed by
      quantitative analysis. Analyses of epithelium and connective tissue revealed a
      significantly higher number of CD1a + LCs in LPLs with dysplasia compared with
      LPLs without dysplasia. Presence of Langerin + LCs in epithelium did not differ
      significantly between LPLs either with or without dysplasia and OSCC. T cells
      were found in significantly increased numbers in LPLs with dysplasia and OSCC.
      The number of CD4+ cells did not differ significantly between LPLs with and
      without dysplasia, but a significant increase was detected when comparing LPLs
      with dysplasia with OSCC. CD8+ cells were significantly more abundant in OSCC and
      LPLs with dysplasia compared with LPLs without dysplasia. Proliferating cells
      (Ki67+) were significantly more abundant in OSCC compared to LPLs with dysplasia.
      Confocal laser scanning microscopy revealed colocalization of LCs and T cells in
      LPLs with dysplasia and in OSCC. LCs and T cells are more numerous in tissue
      compartments with dysplastic epithelial cells and dramatically increase in OSCC.
      This indicates an ongoing immune response against cells with dysplasia.

PMID- 22469081
TI  - Miconazole nitrate: comprehensive profile.

PMID- 22469082
TI  - Niclosamide: comprehensive profile.

PMID- 22469083
TI  - Oxytetracycline: analytical profile.

PMID- 22469084
TI  - Penicillamine: physical profile.

PMID- 22469085
TI  - Penicillamine: analytical profile.

PMID- 22469086
TI  - Penicillamine: adsorption, distribution, metabolism, and elimination profile.

PMID- 22469087
TI  - Primaquine diphosphate: comprehensive profile.

PMID- 22469088
TI  - Valproic Acid and sodium valproate: comprehensive profile.

PMID- 22469089
TI  - Validation of chromatographic methods of analysis.

PMID- 22469090
TI  - Polymorphism and solvatomorphism 2004.

PMID- 22469091
TI  - Preface.

PMID- 22469092
TI  - The effect of wearing custom-made mouthguards on the aeroacoustic properties of
      Japanese sibilant /s/.
AB  - BACKGROUND/AIM: There have been many reports on the discomfort of speech when
      wearing oral appliances. Fricatives articulated in an oral cavity can be
      difficult to pronounce when oral appliances are worn, because the oral cavity is
      partially changed by their installation. Sibilant /s/, one fricative, is
      especially difficult to pronounce when wearing oral appliances. This study
      investigates the effect of the difference in the setting positions of the palatal
      margin of custom-made mouthguards on the aeroacoustic characteristics of sibilant
      /s/. MATERIALS AND METHODS: Eighteen subjects (11 women and seven men)
      participated. The palatal margin of mouthguards was set at the gingival line for
      nine subjects and 4 mm from the line for another nine subjects. Acoustical
      analyses examined the difference of the palatal margins of the mouthguards on the
      autocorrelation coefficient, the zero crossing count, and the spectral peaks of
      sibilant /s/. RESULTS: The results showed that the zero crossing count of the
      waveforms and the spectral peaks of sibilant /s/ were significantly broadened and
      shifted toward the low-frequency range with the mouthguard whose palatal margin
      extended 4 mm from the gingival line than the mouthguard whose palatal margin was
      set at the gingival line. CONCLUSION: We believe that a more appropriate palatal
      mouthguard design for custom-made mouthguards can be made by considering the
      aeroacoustical effects. Our study supported the mouthguard whose palatal margin
      was set at the gingival line by considering the influence on pronouncing sibilant
      /s/. We believe that a more appropriate palatal mouthguard design for custom-made
      mouthguards can be made based on the balance of aeroacoustical effects and
      mechanical requirements.

PMID- 22469093
TI  - Chemical-physical properties of TheraCal, a novel light-curable MTA-like material
      for pulp capping.
AB  - AIM: To evaluate the chemical-physical properties of TheraCal, a new light
      curable pulp-capping material composed of resin and calcium silicate (Portland
      cement), compared with reference pulp-capping materials (ProRoot MTA and Dycal).
      METHODOLOGY: Calcium (Ca) and hydroxyl (OH) ion release over 28 days, solubility
      and water uptake (weight percentage variation, Delta%) at 24 h, cure depth and
      radiopacity of TheraCal, ProRoot MTA and Dycal were evaluated. Statistical
      analysis (P < 0.05) of release of ion was carried out by two-way repeated
      measures anova with Tukey, whilst one-way anova with Tukey test was used for the
      other tests. RESULTS: TheraCal released significantly more calcium than ProRoot
      MTA and Dycal throughout the test period. TheraCal was able to alkalinize the
      surrounding fluid initially to pH 10-11 (3 h-3 days) and subsequently to pH 8-8.5
      (7-14 days). TheraCal had a cure depth of 1.7 mm. The solubility of TheraCal
      (Delta-1.58%) was low and significantly less than that of Dycal (Delta-4.58%) and
      ProRoot MTA (Delta-18.34%). The amount of water absorbed by TheraCal (Delta
      +10.42%) was significantly higher than Dycal (Delta +4.87%) and significantly
      lower than ProRoot MTA (Delta +13.96%). CONCLUSIONS: TheraCal displayed higher
      calcium-releasing ability and lower solubility than either ProRoot MTA or Dycal.
      The capability of TheraCal to be cured to a depth of 1.7 mm may avoid the risk of
      untimely dissolution. These properties offer major advantages in direct pulp
      capping treatments.

PMID- 22469094
TI  - Phenotypic heterogeneity and evidence of a founder effect associated with G6PC3
      mutations in patients with severe congenital neutropenia.

PMID- 22469095
TI  - Mitochondrial and morphological variation of Tilapia zillii in Israel.
AB  - BACKGROUND: Tilapia zillii is widespread in the East Levant inland aquatic
      systems as well as in artificial water reservoirs. In this study we explore the
      genetic and morphological variation of this widespread species, using
      mitochondrial control region sequences and meristic characters. We examine the
      hypothesis that T. zillii's population structure corresponds to the four Israeli
      aquatic systems. RESULTS: Out of seven natural water bodies, only two were found
      to possess genetically divergent populations of T. zillii. In addition to its
      presence in fish farms, the species was found in two artificial recreational
      ponds which were supposed to have been stocked only with other fish species. In
      these two artificial habitats, the haplotype frequencies diverged significantly
      from those of natural populations. Finally, fish from the Dead Sea springs of
      Ne'ot HaKikar appear to differ both genetically and morphologically from fish of
      the same aquatic system but not from fish of other water systems. CONCLUSIONS:
      Our results show that the population structure of T. zillii does not match the
      geography of the Israeli water-basins, with the exception of the Dead Sea and
      Kishon River, when considering natural populations only. The absence of a
      significant divergence between basins is discussed. Our results and observations
      suggest that the Ne'ot HaKikar Dead Sea population and those of artificial ponds
      could have originated from the "hitchhiking" of T. zillii, at the expense of some
      other cultivated tilapiine species.

PMID- 22469096
TI  - Maternal and pathological pregnancy characteristics in customised birthweight
      centiles and identification of at-risk small-for-gestational-age infants: a
      retrospective cohort study.
AB  - OBJECTIVE: To regenerate coefficients for the New Zealand customised birthweight
      centile calculator using an updated birth cohort, and compare the identification
      of at-risk small-for-gestational-age (SGA) infants between full customisation
      (including maternal characteristics) and an ultrasound-based fetal weight and
      infant gender partial customisation. DESIGN: Retrospective cohort study of
      prospectively collected maternity data. SETTING: National Women's Health
      Auckland, New Zealand. POPULATION: Singleton pregnancies in the period 2006-2009;
      n = 24,176. METHODS: Multiple linear regression analysis was performed for full
      customisation (adjusted for gestation, infant gender, maternal characteristics
      and pathological variables) and ultrasound-and-gender customisation (adjusted for
      gestation and infant gender). MAIN OUTCOME MEASURES: Risks of SGA-related
      perinatal death were compared between models. RESULTS: Changes occurred in some
      ethnicity coefficients, including Chinese (-135 g), Tongan (-101 g) and Samoan (
      89 g), and ten ethnicities were added. Overall, full customisation identified SGA
      infants with higher odds of perinatal death (OR 5.6, 95% CI 3.6-8.7) than infants
      classed as SGA by ultrasound-and-gender customisation (OR 2.1, 95% CI 1.4-3.3) (P
      = 0.02). In subgroup analyses, infants classed as SGA by full but not ultrasound
      and-gender customisation (n = 888, 3.4%) had an increased risk of perinatal death
      (RR 4.7, 95% CI 2.7-7.9); however, those identified as SGA by ultrasound-and
      gender customisation alone were not at an increased risk (n = 676, 2.6%, RR 1.1,
      95% CI 0.4-3.6). The population attributable risk (PAR) of SGA-related perinatal
      death was higher for full (49.8%) than for ultrasound-and-gender (43.0%)
      customisation. CONCLUSIONS: Updating the New Zealand customised birthweight
      centile calculator resulted in revised coefficients that better reflect a
      contemporary birth cohort. Inclusion of maternal characteristics in a birthweight
      customisation model increases the detection of SGA infants at risk of perinatal
      death.

PMID- 22469097
TI  - Effect of pluronic acid F-127 on the toxicity towards eukaryotic cells of CSA-13,
      a cationic steroid analogue of antimicrobial peptides.
AB  - AIMS: CSA-13 is an antimicrobial cationic steroid with some toxicity against
      eukaryotic cells. The purpose of this work was to test whether pluronic acid F
      127 could interfere with the toxicity of CSA-13 on human umbilical vein
      endothelial (HUVEC) without modifying its bactericidal activity against
      Pseudomonas aeruginosa. METHODS AND RESULTS: The addition of pluronic acid F-127
      slightly decreased the number of dead cells after exposure to CSA-13. Pluronic
      acid F-127 blocked the permeabilizing effect of CSA-13 on the plasma membrane of
      HUVEC (uptake of ethidium bromide, release of lactate dehydrogenase) without
      modifying its toxic effect on their mitochondrial function (MTT test, uptake of
      tetramethyl rhodamine ethyl ester). CONCLUSION: Pluronic acid F-127 decreased the
      toxicity of CSA-13 against eukaryotic cells without completely protecting them
      from mitochondrial damage at high concentrations of the drug. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work establishes that studies on the toxic effects of
      synthetic antimicrobials on eukaryotic cells should not only focus on the
      permeability of the plasma membrane but also on the integrity of the
      mitochondria.

PMID- 22469098
TI  - The effects of a novel metabotropic glutamate receptor 5 antagonist (AZD2066) on
      transient lower oesophageal sphincter relaxations and reflux episodes in healthy
      volunteers.
AB  - BACKGROUND: Selective metabotropic glutamate receptor 5 (mGluR5) antagonists
      inhibit transient lower oesophageal sphincter relaxations (TLESRs) in animals and
      acid reflux in humans. AIM: To assess the effect of single doses of the mGluR5
      antagonist AZD2066 on TLESRs and reflux in humans. METHODS: Healthy male
      volunteers received AZD2066 13 mg and placebo (part A), or AZD2066 2 mg and
      AZD2066 6 mg and placebo (part B), in a randomised crossover study. Postprandial
      manometry/pH-impedance measurements were taken after each dose. RESULTS: A total
      of 13 individuals completed part A of the study and 19 individuals completed part
      B. There was a significant reduction in the geometric mean number of TLESRs (27%;
      P = 0.02) and the geometric mean number of reflux episodes (51%; P = 0.01) in
      subjects receiving AZD2066 13 mg compared with placebo. Adverse events in
      participants receiving AZD2066 13 mg were mostly related to the nervous system
      [dizziness (3/13); disturbance in attention (3/13)]. Adverse events were
      reversible and of mild intensity. There were no serious adverse events. The
      effects of AZD2066 appeared dose-dependent, with smaller reductions in TLESRs and
      reflux episodes (relative to placebo) and fewer adverse events observed for
      AZD2066 2 mg and AZD2066 6 mg compared with AZD2066 13 mg. CONCLUSION: The mGluR5
      mediated inhibition of TLESRs may be a useful approach for inhibiting gastro
      oesophageal reflux.

PMID- 22469100
TI  - Atrial fibrillation is not associated with rehabilitation outcomes of elderly hip
      fracture patients.
AB  - AIM: To study possible differences in rehabilitation outcomes of patients with
      hip fracture, with and without atrial fibrillation. METHODS: A retrospective
      cohort study comprising 1114 patients, divided into three groups: patients with
      sinus rhythm, paroxysmal atrial fibrillation or chronic atrial fibrillation. All
      patients underwent a standard orthogeriatric care comprising surgical hip repair
      and a rehabilitation course. Main outcome measures included functional status at
      discharge by the Functional Independence Measure, post-fracture functional status
      category and type of postdischarge living arrangement. RESULTS:   Patients with
      atrial fibrillation differed from patients in sinus rhythm by female sex (P =
      0.018), older age (P = 0.008) and higher rates of heart failure (P < 0.001),
      ischemic heart disease (P < 0.001), previous stroke (P < 0.001), and American
      Society of Anesthesiologists score (P < 0.001). No differences were observed
      among the three groups regarding Functional Independence Measure motor and total
      scores. In regression analysis, Mini-Mental State Examination (P < 0.001),
      prefracture status (P < 0.001), postsurgery motor Functional Independence Measure
      (P < 0.0001) and Parkinson's disease (P = 0.009) were predictive of higher motor
      Functional Independence Measure at discharge, whereas atrial fibrillation had no
      predictive value whatsoever. There were no differences among groups in magnitude
      of postfracture change of functional status category or type of postdischarge
      living arrangement. CONCLUSIONS: Discharge motor Functional Independence Measure
      scores, postfracture changes in functional status and in discharge placement are
      similar in hip fracture patients with sinus rhythm, compared with those with
      atrial fibrillation. Atrial fibrillation should not be considered to adversely
      affect the rehabilitation outcome of these patients.

PMID- 22469099
TI  - Drug susceptibility of Mycobacterium tuberculosis Beijing genotype and
      association with MDR TB.
AB  - To determine differences in the ability of Mycobacterium tuberculosis strains to
      withstand antituberculosis drug treatment, we compared the activity of
      antituberculosis drugs against susceptible Beijing and East-African/Indian
      genotype M. tuberculosis strains. Beijing genotype strains showed high rates of
      mutation within a wide range of drug concentrations, possibly explaining this
      genotype's association with multidrug-resistant tuberculosis.

PMID- 22469101
TI  - (2,2'-bipyridyl)-3-3'-diol in nafion: stabilization of unusual ground and excited
      states.
AB  - (2,2'-Bipyridyl)-3-3'-diol (BP(OH)(2)) undergoes excited state intramolecular
      double proton transfer (ESIDPT). The photophysics of this molecule has been
      investigated, in the highly acidic water channels inside nafion membrane. The
      dianionic enolate form of the dye, which is formed only in alkaline conditions in
      neat aqueous solutions, is found to be present in its excited state in native
      nafion membrane at low water content. This surprising phenomenon has been
      explained in the light of loss of protons from the fluorophore to the medium, due
      to increased electrostatic interactions with the pendant sulfonate groups of
      nafion, at the lower water content. This observation fortifies the model of
      microscopic interactions that we have proposed in recent past. Further, the
      ground state of the diketo form, observed only in neat aqueous solutions so far,
      is found to be present in Na(+)-exchanged membranes at lower levels of hydration.
      The steady-state spectral features of the dye is different in (CH(3))(4)N(+)
      exchanged membranes than that of Na(+)-exchanged membranes, unlike in our earlier
      studies with coumarin 102 and 2-(2'-pyridyl)benzimidazole, here we observed
      formation of an unusual ground state in Na(+)-exchanged membranes, while no such
      feature was observed in (CH(3))(4)N(+)-exchanged membranes.

PMID- 22469102
TI  - Quality of life and metabolic disorders in patients with obstructive sleep apnea.
AB  - PURPOSE: Quality of life (QoL) may be poor in patients with sleep apnea depending
      on multifactorial reasons. In this observational study, we examined the factors
      determining QoL in patients with obstructive sleep apnea (OSA) and nonapneic
      snoring subjects. METHODS: Complete assessments were obtained on 111 subjects who
      diagnosed OSA and 18 nonapneic snoring subjects. Fasting blood samples of all of
      subjects were taken to determine insulin resistance (IR) and oral glucose
      tolerance tests were performed to diagnose disorders of glucose metabolism (DGM).
      Quality of life, with short form (SF)-36, and excessive daytime sleepiness, with
      epwort sleepness scale (ESS), were evaluated. RESULTS: The mean age of the
      patients with OSA was higher than that of the nonapneic snoring subjects (48.4 +/
      9.6 years and 43.0 +/- 11.8 years, respectively; p=0.03). BMI was also
      significantly higher in the patients with OSA than in the nonapneic snorers (31.0
      +/- 4.5 and 27.1 +/- 4.0, respectively; p=0.001). The mental health component in
      the patients with OSA was slightly but not significantly lower than the nonapneic
      snoring subjects (p=0.05). A negative correlation among most domains of quality
      of life with scores of ESS, body mass index (BMI), presence of hypertension (HT)
      and DGM was found. Only physicial functioning was negatively correlated with
      apnea hypopnea index (AHI). In linear regression analysis, there were negative
      associations among physical functioning with BMI, presence of HT and DGM while
      there was no association between physicial functioning and AHI. In addition,
      there were negative correlations between mental health component with BMI and
      presence of HT in the multivariate analysis. Obese patients with OSA had lower
      physicial and mental components compared with nonobese patients with OSA.
      CONCLUSION: The impact of OSA on quality of life can be attributed to excessive
      daytime sleepiness. Obesity and metabolic disorders in patients with OSA may also
      negatively affect the quality of life.

PMID- 22469103
TI  - Re: Relationship between mean platelet volume and left ventricular systolic
      function in patients with metabolic syndrome and ST-elevation myocardial
      infarction.

PMID- 22469104
TI  - The effects of selenium and vitamin E on lung tissue in rats with sepsis.
AB  - PURPOSE: In this study we examined the ability of selenium and vitamin E to
      prevent sepsis-induced changes in lung tissue. METHODS: Fifty rats were divided
      into five groups: Group 1: Control group; Group 2: Sepsis group. In this group
      only cecal ligation and perforation (CLP) was performed. Group 3: Selenium group.
      An intraperitoneal dose of 100 ug selenium was given for the first two days
      followed by a daily dose of 40 ug for the next five days. CLP was performed the
      following day. Group 4: Selenium and vitamin E group. In addition to selenium,
      vitamin E was given intramuscularly in a dose of 250 mg/kg/day for seven days.
      CLP was performed the following day. Group 5: Vitamin E group. Vitamin E was
      given intramuscularly in a dose of 250 mg/kg/day for seven days. CLP was
      performed the following day. RESULTS: There were significant differences between
      Group 2 and all other groups in terms of blood gas values (pH, pCO2, SaO2), and
      leukocyte, C-reactive protein (CRP) and glutathione peroxidase levels (p <
      0.005). There was no statistically significant difference between groups 3, 4 and
      5 in terms of histopathological changes in lung tissue (p > 0.05), but all groups
      were significantly different compared with Group 2 (p < 0.05). CONCLUSION: Sepsis
      induced lung tissue damage can be reduced or prevented by pre-treatment with of
      selenium and/or vitamin E in a rat model.

PMID- 22469105
TI  - Telmisartan-induced eNOS gene expression is partially independent of its PPAR
      gamma agonist property.
AB  - PURPOSE: Telmisartan, an angiotensin II receptor blocker (ARB), also acts as an
      activator of peroxisome proliferator-activated receptor-gamma (PPAR-gamma; PPAR
      gamma). Several studies have explored the PPAR-gamma-endothelial nitric oxide
      synthase (eNOS) pathway associated with improvement of endothelial function by
      telmisartan. The ability of telmisartan to induce gene expression and protein
      level of eNOS and PPARgamma in adipocytes was investigated. METHODS: Expression
      of aP2, PPARgamma, eNOS and iNOS genes were measured using the quantitative real
      time polymerase chain reaction. The changes, at the protein level, were explored
      by Western blot, which evaluated the native and phosphorylated eNOS forms, eNOS
      Ser(1177) and eNOS-Thr(495). RESULTS: Adipocytes, exposed to telmisartan,
      exhibited an increase in PPARgamma gene expression but a decrease in protein
      level. Nonetheless, after the exposure to telmisartan, eNOS-Ser(1177)
      phosphorylation, associated with eNOS activity increment, reached its highest
      value while eNOS-Thr(495) phosphorylation, involved in the inhibition of eNOS
      activity, showed its lowest value. CONCLUSION: The results suggest that
      telmisartan preserves eNOS activity via a mechanism that is partially independent
      of the PPARgamma-eNOS pathway in adipocytes.

PMID- 22469106
TI  - Predictors of orthostatic intolerance in healthy young women.
AB  - PURPOSE: Orthostatic intolerance is more prevalent in women. The purpose of this
      investigation was to evaluate the physiological responses of orthostatic tolerant
      and intolerant females to progressive lower body negative pressure (LBNP) and to
      identify predictors of orthostatic tolerance. METHODS: Following baseline
      measurements, eleven healthy, moderately active women (mean age 24 +/- 3 yr)
      underwent an orthostatic challenge involving four 12-minute stages of progressive
      LBNP at -15, -30, -45 and -60 mmHg. Traditional haemodynamic characteristics, as
      well as baroreceptor sensitivity, were analyzed across all stages. RESULTS: Five
      women became presyncopal during the test and were classified as low tolerant (LT)
      while the remaining six were classified as high tolerant (HT). LBNP by group
      (tolerance) interactions were significantly different for stroke volume (P=0.008)
      and the rate of decline (slope) of stroke volume (P=0.03). During the early
      stages of LBNP, the LT group displayed a higher stroke volume than the HT group
      (76.4 +/- 8.6 vs. 60.0 +/- 13.3 mL/beat; P=0.02) yet by the final stage, stroke
      volumes were similar (22.5 +/- 11.9 vs. 22.7 +/- 4.5 mL/beat, P = 0.99).
      Baroreceptor sensitivity, heart rate variability and blood pressure variability
      were not significantly different between the groups. CONCLUSIONS: The results of
      this investigation suggest that orthostatic intolerance in women can be
      identified during the initial stages of an LBNP challenge, as evidenced by a more
      rapid decline in stroke volume.

PMID- 22469107
TI  - Development of a sensitive prognostic scoring system for the evaluation of
      severity of acute-on-chronic hepatitis B liver failure: a retrospective cohort
      study.
AB  - PURPOSE: The purpose of the current study was to establish an objective, simple,
      and sensitive prognostic scoring system for estimating the severity of acute-on
      chronic liver failure in hepatitis B (ACLFB). METHODS: A novel prognostic scoring
      system was calculated from six clinical indices including total bilirubin (TB),
      prothrombin activity (PTA), creatinine (Cr), hepatic encephalopathy (HE),
      infections, and the depth of ascites from 726 patients with ACLFB. Indices were
      scored from 1 to 4 according to their severity. Groups of the same patients were
      scored with three-indices (TB, PTA and Cr), four-indices (TB, PTA, Cr and HE),
      five-indices (TB, PTA, Cr, HE and the depth of ascites) or six-indices (TB, PTA,
      Cr, HE, the depth of ascites, and infections). The differences in the sensitivity
      and specificity of four scoring systems were analyzed. RESULTS: The demarcation
      points of the three-, four-, five- and six-indices scoring systems were 4.62,
      6.12, 7.88 and 9.57, respectively. The analysis of the areas under the receiver
      operating characteristic (ROC) curve indicated that the four-, five- and six
      indices scoring systems were more exact, and objective than the three-indices
      prognostic scoring system. In the six-indices scoring system, the survival rates
      of patients with scores from 2 to 6 was 98.31% (233/237), and the mortality rate
      of patients with scores of 16 and above was 100.00% (140/140), while the
      mortality rates were 8.33% (3/36) and 96.43% (27/28) for those with scores from 7
      to 15, respectively. CONCLUSION: A six-indices scoring system is an objective,
      pertinent, and sensitive system, and may be useful for the prognostic evaluation
      of ACLFB.

PMID- 22469108
TI  - Distinct profile of vascular progenitor attachment to extracellular matrix
      proteins in cancer patients.
AB  - BACKGROUND: Vascular progenitor cells (VPCs) facilitate angiogenesis and initiate
      vascular repair by homing in on sites of damage and adhering to extracellular
      matrix (ECM) proteins. VPCs also contribute to tumor angiogenesis and induce
      angiogenic switching in sites of metastatic cancer. In this study, the binding of
      attaching cells in VPC clusters that form in vitro on specific ECM proteins was
      investigated. METHODS: VPC cluster assays were performed in vitro on ECM proteins
      enriched in cancer cells and in remodelling tissue. Profiles of VPC clusters from
      patients with cancer were compared to healthy controls. The role of VEGF and
      integrin-specific binding of angiogenic attaching cells was addressed. RESULTS:
      VPC clusters from cancer patients were markedly increased on fibronectin relative
      to other ECM proteins tested, in contrast to VPC clusters from control subjects,
      which formed preferentially on laminin. Specific integrin-mediated binding of
      attaching cells in VPC clusters was matrix protein-dependent. Furthermore, cancer
      patients had elevated plasma VEGF levels compared to healthy controls and VEGF
      facilitated preferential VPC cluster formation on fibronectin. Incubating cells
      from healthy controls with VEGF induced a switch from the 'healthy' VPC binding
      profile to the profile observed in cancer patients with a marked increase in VPC
      cluster formation on fibronectin. CONCLUSION: The ECM proteins laminin and
      fibronectin support VPC cluster formation via specific integrins on attaching
      cells and can facilitate patterns of VPC cluster formation that are distinct in
      cancer patients. Larger studies, however, are needed to gain insight on how tumor
      angiogenesis may differ from normal repair processes.

PMID- 22469109
TI  - Management of prolactinomas during pregnancy -- a survey of four Canadian
      provinces.
AB  - PURPOSE: The guidelines for management of prolactinomas during pregnancy are
      mostly based on retrospective evidence or expert opinion. We conducted a survey
      to assess the current trends in management of prolactinomas during pregnancy.
      METHODS: A case-based electronic questionnaire was sent in January 2011 to all
      practicing endocrinologists, in four Canadian provinces: Nova Scotia, New
      Brunswick, Prince Edward Island and British Columbia with three cases of varying
      severity; ranging from a microprolactinomas to a large macroprolactinomas
      compressing the optic chiasm. RESULT: There was a considerable diversity among
      endocrinologists with regards to monitoring and managing prolactinomas during
      pregnancy. In case of microprolactinomas, 94% of specialists would discontinue
      dopamine agonist (DA) therapy upon confirmation of pregnancy, 79% would
      discontinue serum prolactin measurement during pregnancy, and 94% would not
      perform routine pituitary imaging in the absence of new symptoms whereas 32%
      would perform regular formal visual field (VF) testing throughout pregnancy. In
      the case of macroprolactinomas, 65% chose to discontinue DA therapy upon
      confirmation of pregnancy, 30% would either perform regular MRI during pregnancy
      or, if serum prolactin was thought to be elevated out of proportion, with
      clinical judgment and 40% would not perform regular formal VF monitoring during
      pregnancy. In management of large macroprolactinomas, 82% elected to continue DA
      therapy whereas 18% chose surgical excision as the treatment of choice. Forty
      nine percent would perform regular MRI during pregnancy and 94% would perform
      regular formal VF monitoring during pregnancy. CONCLUSION: Among endocrinologists
      there is considerable diversity in management of prolactinomas during pregnancy,
      indicating a need for better consensus and clearer guidelines.

PMID- 22469111
TI  - Obesity treatment by hypothalamic transplantation.

PMID- 22469112
TI  - Mesenchymal stromal cell-based treatment of jaw osteoradionecrosis in Swine.
AB  - Jaw osteoradionecrosis (ORN) is a common and serious complication of radiation
      therapy for head and neck cancers. Bone marrow mesenchymal stromal cells (BMMSCs)
      are multipotent postnatal stem cells and have been widely used in clinical
      therapies. In the present study, we generated the  mandibular ORN model in swine
      using a combination of single-dose 25-Gy irradiation and tooth extraction. A
      typical ORN phenotype, including loss of bone regeneration capacity and collagen
      collapse with the obliteration of vessels, gradually appeared after irradiation.
      After autologous BMMSC  transplantation, new bone and vessels were regenerated,
      and the advanced mandibular ORN was treated successfully. In summary, we
      developed a swine model of jaw ORN, and our results indicate that autologous
      BMMSC transplantation may be a promising therapeutic approach for ORN.

PMID- 22469110
TI  - What is dynapenia?
AB  - Dynapenia (pronounced dahy-nuh-pe-ne-a, Greek translation for poverty of
      strength, power, or force) is the age-associated loss of muscle strength that is
      not caused by neurologic or muscular diseases. Dynapenia predisposes older adults
      to an increased risk for functional limitations and mortality. For the past
      several decades, the literature has largely focused on muscle size as the primary
      cause of dynapenia; however, recent findings have clearly demonstrated that
      muscle size plays a relatively minor role. Conversely, subclinical deficits in
      the structure and function of the nervous system and/or impairments in the
      intrinsic force-generating properties of skeletal muscle are potential
      antecedents to dynapenia. This review highlights in the contributors to dynapenia
      and the etiology and risk factors that predispose individuals to dynapenia. In
      addition, we address the role of nutrition in the muscular and neurologic systems
      for the preservation of muscle strength throughout the life span.

PMID- 22469113
TI  - Who benefits from health services in South Africa?
AB  - South Africa is considering major health service restructuring to move towards a
      universal system. This calls for understanding the challenges in the existing
      health system. The paper, therefore, comprehensively evaluates an aspect of
      current health system performance - the benefit incidence of health services. It
      seeks to understand how the benefits from using health services in South Africa
      are currently distributed across socio-economic groups. Using a nationally
      representative household survey, results show that lower socio-economic groups
      benefit less than their richer counterparts from both public and private sector
      health services, and that the distribution of service benefits is not in line
      with their need for care.

PMID- 22469114
TI  - Biology-driven medicine: tissue matters.

PMID- 22469115
TI  - Standardisation of clinical breast-density measurement.

PMID- 22469116
TI  - Crowding out cancer.

PMID- 22469117
TI  - Absent benefit of accelerated concomitant chemoradiotherapy.

PMID- 22469119
TI  - Screening of symptomatic women for ovarian cancer.

PMID- 22469120
TI  - Screening of symptomatic women for ovarian cancer.

PMID- 22469121
TI  - Screening of symptomatic women for ovarian cancer.

PMID- 22469123
TI  - Second-line erlotinib for non-small-cell lung cancer.

PMID- 22469125
TI  - Management of elderly patients with breast cancer: updated recommendations of the
      International Society of Geriatric Oncology (SIOG) and European Society of Breast
      Cancer Specialists (EUSOMA).
AB  - As the mean age of the global population increases, breast cancer in older
      individuals will be increasingly encountered in clinical practice. Management
      decisions should not be based on age alone. Establishing recommendations for
      management of older individuals with breast cancer is challenging because of very
      limited level 1 evidence in this heterogeneous population. In 2007, the
      International Society of Geriatric Oncology (SIOG) created a task force to
      provide evidence-based recommendations for the management of breast cancer in
      elderly individuals. In 2010, a multidisciplinary SIOG and European Society of
      Breast Cancer Specialists (EUSOMA) task force gathered to expand and update the
      2007 recommendations. The recommendations were expanded to include geriatric
      assessment, competing causes of mortality, ductal carcinoma in situ, drug safety
      and compliance, patient preferences, barriers to treatment, and male breast
      cancer. Recommendations were updated for screening, primary endocrine therapy,
      surgery, radiotherapy, neoadjuvant and adjuvant systemic therapy, and metastatic
      breast cancer.

PMID- 22469126
TI  - Tattoos, inks, and cancer.
AB  - The introduction in the dermis of exogenous pigments and dyes to obtain a
      permanent design (tattooing) represents a unique in-vivo situation, where a large
      amount of metallic salts and organic dyes remain in the skin for the lifetime of
      the bearer. The potential local and systemic carcinogenic effects of tattoos and
      tattoo inks remain unclear. Several studies have shed light on the presence of
      potential carcinogenic or procarcinogenic products in tattoo inks. We extensively
      reviewed the literature and found 50 cases of skin cancer on tattoos: 23 cases of
      squamous-cell carcinoma and keratoacanthoma, 16 cases of melanoma, and 11 cases
      of basal-cell carcinoma. The number of skin cancers arising in tattoos is
      seemingly low, and this association has to be considered thus far as
      coincidental.

PMID- 22469127
TI  - Evaluation of novel radiotherapy technologies: what evidence is needed to assess
      their clinical and cost effectiveness, and how should we get it?
AB  - Technical innovations in radiation oncology--eg, intensity-modulated
      radiotherapy, stereotactic radiotherapy, and particle therapy--can be developed
      rapidly and introduced into the clinic even when costs associated with their use
      are much higher than those for conventional radiotherapy. Although clinical
      benefit is expected on the basis of superior biological and physical
      characteristics, data for clinical effectiveness of new radiotherapy techniques
      are scarce. Evidence from randomised clinical trials would be ideal but such
      studies focus mostly on new drugs. High investment costs and modifications over
      time make evaluation of novel radiotherapy technologies in clinical trials more
      complex. Here, we propose an algorithm for evaluation of the clinical and cost
      effectiveness of novel radiotherapy technologies. We suggest situations when
      randomised trials might be feasible and the type of trial that should be
      undertaken when they are not. Furthermore, we discuss the usefulness of dose
      distribution models for estimation of expected clinical benefit and for selection
      of the patients' population with the highest expected benefit. Economic
      modelling, including the approach of real options analysis, can inform whether
      implementation of a technology should begin (based on available evidence) or be
      delayed (until further data are available), and it can indicate the best trial
      design and required sample size.

PMID- 22469128
TI  - Genetic heterogeneity and cancer drug resistance.
AB  - Despite the success of targeted therapies in the treatment of cancer, the
      development of resistance limits the ability to translate this method into a
      curative treatment. The mechanisms of resistance have traditionally been thought
      of as intrinsic (ie, present at baseline) or acquired (ie, developed after
      initial response). Recent evidence has challenged the notion of acquired
      resistance. Although cancers are traditionally thought to be clonal, there is now
      evidence of intra-tumour genetic heterogeneity in most cancers. The clinical
      pattern of acquired resistance in many circumstances represents outgrowth of
      resistant clones that might have originally been present in the primary cancer at
      low frequency but that have expanded under the selective pressure imposed by
      targeted therapies. Here, we describe the potential role of clonal heterogeneity
      in resistance to targeted therapy, discuss genetic instability as one of its
      causes, and detail approaches to tackle intra-tumour heterogeneity in the clinic.

PMID- 22469129
TI  - Comparison of Escherichia coli ST131 pulsotypes, by epidemiologic traits, 1967
      2009.
AB  - Escherichia coli sequence type 131 (ST131), an emerging disseminated public
      health threat, causes multidrug-resistant extraintestinal infections. Among 579
      diverse E. coli ST131 isolates from 1967-2009, we compared pulsotypes (>94%
      similar XbaI pulsed-field gel electrophoresis profiles) by collection year,
      geographic origin, source, and antimicrobial drug-resistance traits. Of 170
      pulsotypes, 65 had >2 isolates and accounted for 85% of isolates. Although
      extensively dispersed geographically, pulsotypes were significantly source
      specific (e.g., had little commonality between humans vs. foods and food
      animals). The most prevalent pulsotypes were associated with recent isolation,
      humans, and antimicrobial drug resistance. Predominant pulsotype 968 was
      associated specifically with fluoroquinolone resistance but not with extended
      spectrum beta-lactamase production or bla(CTX-M-15). Thus, several highly
      successful antimicrobial drug-resistant lineages within E. coli ST131 have
      recently emerged and diffused extensively among locales while maintaining a
      comparatively restricted host/source range. Identification of factors
      contributing to this behavior of ST131 could help protect public health.

PMID- 22469131
TI  - Inhibition of phosphodiestrase 9 induces cGMP accumulation and apoptosis in human
      breast cancer cell lines, MCF-7 and MDA-MB-468.
AB  - OBJECTIVES: Phosphodiesterase 9 (PDE9) is a major isoform of phosphodiesterase
      hydrolysing cGMP and plays a key role in proliferation of cells, their
      differentiation and apoptosis, via intracellular cGMP signalling. The study
      described here was designed to investigate expression, activity and apoptotic
      effect of PDE9 on human breast cancer cell lines, MCF-7 and MDA-MB-468. MATERIALS
      AND METHODS: Activity and expression of PDE9 were examined using colorimetric
      cyclic nucleotide phosphodiesterase assay and real-time RT-PCR methods
      respectively; cGMP concentration was also measured. MTT viability test, annexin V
      FITC staining, Hoechst 33258 staining and caspase3 activity assay were used to
      detect apoptosis. RESULTS: Treatment of both cell lines with BAY 73-6691 lead to
      reduction in PDE9 mRNA expression, PDE9 cGMP-hydrolytic activity and elevation of
      the intracellular cGMP response. BAY 73-6691 significantly reduced cell
      proliferation in a dose- and time-dependent manner and caused marked increase in
      apoptosis through caspase3 activation. CONCLUSION: Our results revealed that BAY
      73-6691 induced apoptosis in these breast cancer cell lines through the cGMP
      pathway. These data suggest that BAY 73-6691 could be utilized as an agent in
      treatment of breast cancer.

PMID- 22469132
TI  - A qualitative study on healthcare professionals' perceived barriers to insulin
      initiation in a multi-ethnic population.
AB  - BACKGROUND: Nationwide surveys have shown that the prevalence of diabetes rates
      in Malaysia have almost doubled in the past ten years; yet diabetes control
      remains poor and insulin therapy is underutilized. This study aimed to explore
      healthcare professionals' views on barriers to starting insulin therapy in people
      with type 2 diabetes. METHODS: Healthcare professionals consisting of general
      practitioners (n = 11), family medicine specialists (n = 10), medical officers (n
      = 8), government policy makers (n = 4), diabetes educators (n = 3) and
      endocrinologists (n = 2) were interviewed. A semi-structured topic guide was used
      to guide the interviews by trained facilitators. The interviews were transcribed
      verbatim and analysed using a thematic analysis approach. RESULTS: Insulin
      initiation was found to be affected by patient, healthcare professional and
      system factors. Patients' barriers include culture-specific barriers such as the
      religious purity of insulin, preferred use of complementary medication and
      perceived lethality of insulin therapy. Healthcare professionals' barriers
      include negative attitudes towards insulin therapy and the 'legacy effect' of old
      insulin guidelines; whilst system barriers highlight the lack of resources,
      language and communication challenges. CONCLUSIONS: Tackling the issue of insulin
      initiation should not only happen during clinical consultations. It requires
      health education to emphasise the progressive nature of diabetes and the
      eventuality of insulin therapy at early stage of the illness. Healthcare
      professionals should be trained how to initiate insulin and communicate
      effectively with patients from various cultural and religious backgrounds.

PMID- 22469133
TI  - Inflammation-mediated genomic instability: roles of activation-induced cytidine
      deaminase in carcinogenesis.
AB  - Chronic inflammation is a strong risk factor for the development of cancer. Many
      previous studies have demonstrated that a transcriptional factor, nuclear factor
      (NF)-kappaB, plays an important role in the association between inflammation and
      cancer development, particularly tumor promotion and tumor progression. Although
      it is well recognized that cancer develops via stepwise accumulation of genetic
      aberrations, the mechanisms underlying the generation of these genetic
      alterations in normal epithelial cells under inflammatory conditions are not
      known. We recently demonstrated that pathogenic bacterial or viral factors and
      the subsequent inflammatory reactions lead to the aberrant expression of a DNA
      mutator enzyme, activation-induced cytidine deaminase (AID), in various
      epithelial cells via NF-kappaB activation, which causes the accumulation of
      genetic alterations in tumor-related genes. AID activation is widely observed in
      gastrointestinal tissues with cancer-associated inflammation, such as chronic
      viral hepatitis, Helicobacter pylori-related gastritis, Barrett's esophagus and
      inflammatory bowel disease. Furthermore, a deficiency of endogenous AID
      expression reduces both accumulation of somatic mutations in tumor-related genes
      and tumor incidence in a mouse model of inflammation-associated cancer
      development. These findings strongly suggest that AID plays an integral role in
      inflammation-associated carcinogenesis and is therefore a potential target
      molecule for the prevention and treatment of cancers.

PMID- 22469134
TI  - Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma.
AB  - Hodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) show
      constitutive activation of nuclear factor (NF)-kappaB. Several genetic lesions
      contribute to this deregulated NF-kappaB activity. Here, we analysed two further
      NF-kappaB regulators for genetic lesions, the inhibitory factor TRAF3 and the key
      signalling component of the alternative NF-kappaB pathway, MAP3K14 (NIK). Single
      nucleotide polymorphism (SNP) array analysis of cHL cell lines revealed a
      uniparental disomy of the long arm of chromosome 14 associated with a biallelic
      deletion of TRAF3 located on this chromosome in cell line U-HO1. Cloning of the
      deletion breakpoint showed a 123 371 bp deletion. No inactivating mutations of
      TRAF3 were found in six other cHL cell lines or in microdissected HRS cells from
      seven cHL. However, in primary cHL samples interphase cytogenetic analyses
      revealed signal patterns indicating monoallelic deletion of TRAF3 in 3/20 other
      cases. SNP array analysis revealed a gain of copy number for MAP3K14 in three cHL
      cell lines. Gains of MAP3K14 were detected in 5/16 cases of primary cHL. In
      conclusion, in rare instances, HRS cells harbour inactivating mutations of the
      TRAF3 gene and recurrently show gains of MAP3K14, indicating that more components
      of NF-kappaB signalling show genetic lesions in HRS cells than previously known.

PMID- 22469135
TI  - Comparison of GOHAI and OHIP-14 measures in relation to objective values of oral
      function in elderly Japanese.
AB  - OBJECTIVES: The aims of this study were to assess the correlations between the
      Geriatric Oral Health Assessment Index (GOHAI) and the Oral Health Impact Profile
      14 (OHIP-14) and to examine which survey is more sensitive to objectively
      measured oral function in the Japanese elderly. METHODS: The subjects were 290
      community-dwelling, cognitively healthy, and independently living people over the
      age of 60 years (mean: 66.3 years). Measures included the GOHAI and OHIP-14
      questionnaires, as well as self-rating of general and oral health, dry mouth,
      number of residual teeth, and objective values of occlusal force, masticatory
      performance, and salivary flow rate. Bivariate and linear regression analyses
      were used to identify which of these variables predicted GOHAI and OHIP-14
      scores. RESULTS: Spearman's correlation coefficient between the GOHAI and OHIP-14
      scores was 0.728 (P < 0.001), although the OHIP-14 showed a greater number of 0
      scores, suggesting a greater floor effect. At the bivariate level, self-rating of
      general and oral health, dry mouth, number of residual teeth, occlusal force, and
      masticatory performance were associated with GOHAI and OHIP-14 scores. Multiple
      linear regression analyses showed that after controlling for the other
      significant variables, both the occlusal force (standardized regression
      coefficient [beta] = -0.164, P = 0.004) and masticatory performance (beta = 
      0.125, P = 0.019) had significant associations with the GOHAI score, whereas this
      association was not found with the OHIP score. CONCLUSIONS: Although the GOHAI
      and OHIP-14 had a strong correlation, the GOHAI was more sensitive to the
      objective values of oral functions among independently living elderly persons in
      Japan.

PMID- 22469138
TI  - Critical Compilation of pK(a) Values for Pharmaceutical Substances.

PMID- 22469137
TI  - Accuracy of bone surface size and cortical layer thickness measurements using
      cone beam computerized tomography.
AB  - OBJECTIVES: The purpose of this study was to determine the accuracy of Cone Beam
      Computerized Tomography (CBCT) reconstructions in displaying bone surface size
      and cortical layer thickness. MATERIALS AND METHODS: Two fresh frozen cadaver
      heads were scanned using a CBCT (i-CAT(TM) 3D Imaging System; Imaging Sciences
      International Inc.). The mandibles were sectioned and digitalized for
      histological evaluation. Dimensions as measured on these sections were compared
      with CBCT measurements of the same region with the use of 3D image-based planning
      software (Procera System NobelGuide(TM); Nobel Biocare). To allow optimal
      comparison between histological and CBCT sections, reference markers were placed
      into the mandibles. The Student t-test was utilized to analyze the data.
      Differences with P-values <0.05 were considered significant. RESULTS: The total
      height and width of the mandibular body, as measured on CBCT views, were larger
      compared with the histological values with a maximum difference of 0.33 mm (SD +/
      0.34). Cortical thickness measurements were significantly thicker on CBCT
      sections (P < 0.006) with absolute differences ranging up to +/-0.63 mm (SD +/
      0.28) and relative differences ranging up to 82.6%. CONCLUSION: CBCT images (i
      CAT 3D Imaging System), viewed on the planning software Procera System
      NobelGuide, tend to overestimate the anatomical truth in assessing both bone
      height and width; especially cortical thicknesses are depicted thicker than in
      reality. When using CBCT images for presurgical assessment, one should be aware
      of this phenomenon of exaggeration of dimensions.

PMID- 22469139
TI  - Appendix a.

PMID- 22469140
TI  - Appendix B.

PMID- 22469142
TI  - Foreword.

PMID- 22469144
TI  - Preface.

PMID- 22469145
TI  - Mayaro virus infection in traveler returning from Amazon Basin, northern Peru.

PMID- 22469147
TI  - Organic sulfur metabolisms in hydrothermal environments.
AB  - Sulfur is central to the metabolisms of many organisms that inhabit extreme
      environments. While biotic and abiotic cycling of organic sulfur compounds has
      been well documented in low-temperature anaerobic environments, cycling of
      organic sulfur in hydrothermal environments has received less attention. Recently
      published thermodynamic data have been used to estimate aqueous alkyl thiol and
      sulfide activities in deep-sea hydrothermal systems. Here we use geochemical
      mixing models to predict fluid compositions that result from mixing end-member
      hydrothermal fluid from the East Pacific Rise with bottom seawater. These fluid
      compositions are combined with estimates of methanethiol and dimethylsulfide
      activities to evaluate energy yields for potential organic sulfur-based
      metabolisms under hydrothermal conditions. Aerobic respiration has the highest
      energy yields (over -240 kJ/mol e-) at lower temperature; however, oxygen is
      unlikely to persist at high temperatures, restricting aerobic respiration to
      mesophilic communities. Nitrite reduction to N2 has the highest energy yields at
      higher temperatures (greater than ~40  degrees C). Nitrate and nitrite reduction
      to ammonium also yield significant energy (up to -70 kJ/mol e-). Much lower, but
      still feasible energy yields are calculated for sulfate reduction,
      disproportionation, and reduction with H2. Organic compound family and the
      activity of methanethiol and dimethylsulfide were less important than metabolic
      strategy in determining overall energy yields. All metabolic strategies
      considered were exergonic within some portion of the mixing regime suggesting
      that organic sulfur-based metabolisms may be prevalent within deep-sea
      hydrothermal vent microbial communities.

PMID- 22469146
TI  - Human periprostatic adipose tissue promotes prostate cancer aggressiveness in
      vitro.
AB  - BACKGROUND: Obesity is associated with prostate cancer aggressiveness and
      mortality. The contribution of periprostatic adipose tissue, which is often
      infiltrated by malignant cells, to cancer progression is largely unknown. Thus,
      this study aimed to determine if periprostatic adipose tissue is linked with
      aggressive tumor biology in prostate cancer. METHODS: Supernatants of whole
      adipose tissue (explants) or stromal vascular fraction (SVF) from paired fat
      samples of periprostatic (PP) and pre-peritoneal visceral (VIS) anatomic origin
      from different donors were prepared and analyzed for matrix metalloproteinases
      (MMPs) 2 and 9 activity. The effects of those conditioned media (CM) on growth
      and migration of hormone-refractory (PC-3) and hormone-sensitive (LNCaP) prostate
      cancer cells were measured. RESULTS: We show here that PP adipose tissue of
      overweight men has higher MMP9 activity in comparison with normal subjects. The
      observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue
      explants, likely reveal the contribution of adipocytes plus stromal-vascular
      fraction (SVF) as opposed to SVF alone. MMP2 activity was higher for PP when
      compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP
      adipose tissue explants, increased proliferative and migratory capacities were
      observed, but not in the presence of SVF. Conversely, when LNCaP cells were
      stimulated with PP explants CM, we found enhanced motility despite the inhibition
      of proliferation, whereas CM derived from SVF increased both cell proliferation
      and motility. Explants culture and using adipose tissue of PP origin are most
      effective in promoting proliferation and migration of PC-3 cells, as respectively
      compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells,
      while explants CM cause increased migration compared to SVF, the use of PP
      adipose tissue to generate CM result in the increase of both cellular
      proliferation and migration. CONCLUSIONS: Our findings suggest that the PP depot
      has the potential to modulate extra-prostatic tumor cells' microenvironment
      through increased MMPs activity and to promote prostate cancer cell survival and
      migration. Adipocyte-derived factors likely have a relevant proliferative and
      motile role.

PMID- 22469148
TI  - Right-sided implantation and subpectoral position are predisposing factors for
      fracture of a 6.6 French ICD lead.
AB  - BACKGROUND: The Medtronic Sprint Fidelis (Medtronic Inc., Minneapolis, MN, USA)
      lead family is associated with an unacceptable incidence of premature lead
      failure. There are limited data on risk factors for lead fracture. We
      hypothesized that factors leading to potential increased forces on the lead
      related to device implantation or technique may be associated with premature lead
      failure. METHODS: We reviewed the implant data from our group and identified 176
      patients who received active fixation Medtronic Fidelis (Model 6931, single coil
      and Model 6949, dual coil) leads. Implant data, including age, sex, venous access
      site, implant side, implant location, and number of venous leads were reviewed.
      Hospital, pacemaker clinic, and Medtronic registration databases were reviewed
      for evidence of lead failure, replacement, or abandonment. Data was evaluated in
      univariate and multivariate regression analyses. RESULTS: Of the 176 leads
      implanted, 10 (5.7%) were noted to develop malfunction. This presented as
      inappropriate shocks from sensed noise or elevated impedance measurements. Of the
      above noted implant features, only right-sided (vs left-sided) implant (hazard
      ratio [HR] 18.8, 95% confidence intervals [CI] 3.8, 93.3), and subpectoral
      implant (vs prepectoral; HR 14.31, 95% CI 3.2, 64.0) were predictive of lead
      failure in maximally adjusted models. CONCLUSIONS: We have identified both right
      sided implantation and subpectoral generator positioning as factors associated
      with premature lead malfunction in Fidelis active fixation leads. Clinical
      decisions regarding patient management should incorporate these findings in
      regard to lead replacement in high-risk patients.

PMID- 22469149
TI  - What's new--what's changing in prostate cancer? Abstracts of an interactive one
      day educational meeting of the Royal Society of Medicine Sections of Oncology.
      February 17, 2012. London, United Kingdom.

PMID- 22469150
TI  - Occupational assessment of exposure to organic solvents in an adhesive producing
      company in Sfax, Tunisia.

PMID- 22469151
TI  - Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet.
AB  - Evidence in support of a novel lyssavirus was obtained from brain samples of an
      African civet in Tanzania. Results of phylogenetic analysis of nucleoprotein gene
      sequences from representative Lyssavirus species and this novel lyssavirus
      provided strong empirical evidence that this is a new lyssavirus species,
      designated Ikoma lyssavirus.

PMID- 22469152
TI  - Mapping the pollutants in surface riverine flood plume waters in the Great
      Barrier Reef, Australia.
AB  - The extent of flood plume water over a 10 year period was mapped using quasi-true
      colour imagery and used to calculate long-term frequency of occurrence of the
      plumes. The proportional contribution of riverine loads of dissolved inorganic
      nitrogen, total suspended sediments and Photosystem-II herbicides from each
      catchment was used to scale the surface exposure maps for each pollutant. A
      classification procedure was also applied to satellite imagery (only Wet Tropics
      region) during 11 flood events (2000-2010) through processing of level-2 ocean
      colour products to discriminate the changing characteristics across three water
      types: "primary plume water", characterised by high TSS values; "secondary plume
      water", characterised by high phytoplankton production as measured by elevated
      chlorophyll-a (chl-a), and "tertiary plume water", characterised by elevated
      coloured dissolved and detrital matter (CDOM+D). This classification is a first
      step to characterise flood plumes.

PMID- 22469153
TI  - Managing nitrogen inputs into seagrass meadows near a coastal city: flow-on from
      research to environmental improvement plans.
AB  - Increased human habitation has led to a 30 to 50-fold increase in nutrient loads
      to the coastal waters of Adelaide, resulting in the loss of over 5000 ha of
      seagrass meadows. The rate of loss since the 1940s has been irregular, averaging
      85 ha yr(-1), marked by a substantial peak between 1971 and 1977. A modelling
      approach allowed comparison of the annual input with the annual uptake rates for
      the different biotic components in the seagrass bed. In 2005, the estimated
      uptake of ammonium (465 t yr(-1)) and nitrate (3.04 t yr(-1)) by the seagrass and
      associated epiphytes in the Adelaide region accounted for 31% of the ammonium and
      <1% of the nitrate that is currently discharged into the coastal waters.
      Environment Improvement Programs, such as the one implemented in 1996, may reduce
      the total nitrogen loads to 700 t yr(-1), possibly stemming further losses and
      facilitating recolonisation of new seagrass.

PMID- 22469154
TI  - Prevalence and composition of fishing gear debris in the nests of northern
      gannets (Morus bassanus) are related to fishing effort.
AB  - Bycatch and indirect mortality associated with global fishing operations affect
      non-target species. Northern gannets (Morus bassanus) and other seabirds
      incorporate marine debris, much of it originating in fisheries, into their nests,
      at times resulting in entanglement. We compared the prevalence and composition of
      marine debris in nests at two gannet colonies in Newfoundland before and after a
      basin-wide ground fish closure in 1992, and at the species' largest colony in the
      Gulf of St. Lawrence, where fishing effort is low. The proportion of nests with
      marine debris decreased following the fishery closure, and the proportion of
      nests with fishing gear was related exponentially to the number of gillnets set
      around breeding colonies. Assessing the composition of gannet nests could provide
      a useful index of the prevalence of fishing debris and could be used to assess
      entanglement risk of other animals in the marine environment over decadal scales.

PMID- 22469155
TI  - Methotrexate for psoriasiform lesions associated with anti-tumour necrosis factor
      therapy in inflammatory bowel disease.
AB  - BACKGROUND: Psoriasiform lesions associated with anti-tumour necrosis factor
      (TNF) therapy are frequent in patients with inflammatory bowel disease (IBD).
      While methotrexate is the most frequently used systemic treatment for psoriasis,
      its efficacy for psoriasiform lesions related to anti-TNF therapy remains
      unknown. AIMS: To assess the efficacy of methotrexate for psoriasiform lesions
      associated with anti-TNF therapy refractory to topical therapy in IBD patients.
      METHODS: The charts of eight patients from the Nancy IBD cohort who developed
      psoriasiform lesions on anti-TNF therapy were reviewed. Clinical response was
      defined as a decrease of more than 50% in the lesions covering surface. All
      patients were followed up by the same experienced dermatologist. RESULTS: Eight
      women (seven Crohn's disease) were followed up for a median duration of 29 months
      (range, 20-45). Of the eight patients receiving methotrexate, three were primary
      responders without discontinuation of anti-TNF agents. Only one patient had a
      sustained response at final follow-up and was able to continue both methotrexate
      and anti-TNF therapy. Of the two other primary responders, one patient had to
      discontinue anti-TNF because of severe psoriasiform lesions, whereas the other
      one continued anti-TNF therapy despite persistent skin lesions at final follow
      up. Among the five primary nonresponders, four patients had to stop anti-TNF
      treatment due to disabling skin lesions. CONCLUSION: Methotrexate does not appear
      effective in treating psoriasiform lesions associated with anti-TNF therapy
      refractory to topical therapy in IBD.

PMID- 22469156
TI  - Comprehensive sampling reveals circumpolarity and sympatry in seven mitochondrial
      lineages of the Southern Ocean crinoid species Promachocrinus kerguelensis
      (Echinodermata).
AB  - Sampling at appropriate spatial scales in the Southern Ocean is logistically
      challenging and may influence estimates of diversity by missing intermediate
      representatives. With the assistance of sampling efforts especially influenced by
      the International Polar Year 2007-2008, we gathered nearly 1500 specimens of the
      crinoid species Promachocrinus kerguelensis from around Antarctica. We used
      phylogeographic and phylogenetic tools to assess its genetic diversity,
      demographic history and evolutionary relationships. Six phylogroups (A-F)
      identified in an earlier study are corroborated here, with the addition of one
      new phylogroup (E2). All phylogroups are circumpolar, sympatric and eurybathic.
      The phylogeny of Promachocrinus phylogroups reveals two principal clades that may
      represent two different cryptic species with contrasting demographic histories.
      Genetic diversity indices vary dramatically within phylogroups, and within
      populations, suggesting multiple glacial refugia in the Southern Ocean: on the
      Kerguelen Plateau, in the East Weddell Sea and the South Shetland Islands
      (Atlantic sector), and on the East Antarctic continental shelf in the Dumont
      d'Urville Sea and Ross Sea. The inferences of gene flow vary among the
      phylogroups, showing discordant spatial patterns. Phylogroup A is the only one
      found in the Sub-Antarctic region, although without evident connectivity between
      Bouvet and Kerguelen populations. The Scotia Arc region shows high levels of
      connectivity between populations in most of the phylogroups, and barriers to gene
      flow are evident in East Antarctica.

PMID- 22469157
TI  - [Good physician professionalism is more than medical professionalism].

PMID- 22469158
TI  - [Radiological intervention in venous diseases].

PMID- 22469159
TI  - [Too many difficult words in printed communications from the health-care system
      to laypeople].
AB  - INTRODUCTION: It is vital that patients understand the language used in leaflets
      in medicine packages and in information for participation in medical research.
      The aim of the study was to determine the proportion of Danes with reading skills
      corresponding to 9-10 years of schooling who understand the language used by
      health-care professionals in materials targeted at laypeople. MATERIAL AND
      METHODS: Based on a study of ordinary citizens' understanding of the language
      used in printed communication from Danish authorities we tested the words used in
      printed matters from the health-care system; specifically information forms and
      questionnaires from research protocols submitted to the local ethics committee.
      In addition 44 students from adult learning centres were asked to comment on
      their understanding of words via individual interviews about patient leaflets
      from medicine packages. In total 143 common words were selected and tested with
      404 other students. A word would be considered difficult if less than 90% of the
      students understood its meaning. RESULTS: Of the 143 words, 14 (10%) were
      understood correctly by less than 10% of the students, 33 (23%) by 10-25%, 46
      (32%) by 25-50%, and 50 (35%) by more than half. No words were understood by 90%
      or more. CONCLUSION: Ordinary words are difficult to understand when used in a
      medical context. Our study did not identify any rule or principle to predict
      which words laypeople understand. Consequently printed communications from the
      health-care system to laypeople must be pre-tested by end users to ensure
      comprehension.

PMID- 22469160
TI  - [Acute iliofemoral deep venous thrombosis should be treated with catheter
      directed thrombolysis].
AB  - Treatment of acute iliofemoral deep venous thrombosis (DVT) with catheter
      directed thrombolysis (CDT) has been performed in Denmark since 1999. The purpose
      of CDT is to dissolve thrombus and to restore the venous lumen as fast as
      possible and thereby save venous valve function and prevent postthrombotic
      syndrome. Danish studies have shown that treatment of acute iliofemoral DVT using
      CDT results in good patency, preserves venous valve function, reduces the
      frequency of PTS, and is associated with a higher quality of life.

PMID- 22469161
TI  - [Telehealthcare for chronic obstructive pulmonary disease].
AB  - A Cochrane review of telehealthcare in chronic obstructive pulmonary disease
      (COPD) has found telehealthcare to have a positive effect on quality of life in
      patients with COPD and reduced health-care contacts. In this comment, the fact
      that the reviewed studies all contain interventions in which telehealthcare is
      only one part is highlighted. No studies comparing complex interventions with and
      without telehealthcare exist in COPD and more studies are therefore clearly
      needed before further implementation of this technology.

PMID- 22469162
TI  - [Varying effect of telemedicine in the treatment of chronic obstructive pulmonary
      disease--a systematic review].
AB  - A systematic review of existing evidence on the efficiency of telemedicine
      solutions for patients with chronic obstructive pulmonary disease (COPD) was
      performed. A systematic literature search was conducted in five relevant
      databases followed by evaluation of methodology and results in selected studies.
      Nine RCT trials of varying quality were identified. The selected studies were
      mostly multimodal with telemedicine as part of a more complex intervention.
      Benefits of using telemedicine solutions for patients with COPD are not yet
      clear, but in some multimodal studies with telemedicine as part of the solution a
      positive effect on hospital admissions, emergency room visits and contacts to
      primary care may be seen. Larger studies are needed.

PMID- 22469163
TI  - [Contact from general practitioners to unvaccinated girls can increase HPV
      vaccination consent].
AB  - The aim of the study was to evaluate the impact of general practitioners (GPs)
      follow-up of unvaccinated girls in the Danish Human Papillomavirus catch-up
      vaccination programme. Telephone interviews were conducted with the GPs to
      explore their follow-up procedure. The girls were divided into two groups: 1)
      girls contacted by their GP and 2) girls not contacted by their GP. Ten months
      later 61% of the girls, who had been contacted, had started vaccination in the
      follow-up group compared to 53% of girls, who had not been contacted (p < 0.02).
      Follow-up by GPs increased the likelihood of subsequent vaccination in a group of
      unvaccinated girls.

PMID- 22469164
TI  - [Pneumomediastinum induced by sniffed cocaine].
AB  - The increasing availability and use of cocaine stresses the importance that
      physicians are aware of the medical complications of the abuse. This case report
      describes a 24 year-old man who got chest pain after the snorting of 6 g of
      cocaine. A chest X-ray revealed a pneumomediastinum, which was confirmed by a
      computed tomography of the thorax. Pneumomediastinum secondary to cocaine
      insufflations is described as a benign condition. Adequate therapy is painkillers
      and observation, when life-threatening condition such as oesophageal rupture is
      excluded.

PMID- 22469165
TI  - [Cystic tumour of the atrioventricular node in a nine year-old girl].
AB  - Cystic tumour of the atrioventricular node (CTAVN) is a rare type of cardiac
      tumour. We report a case of a previously healthy nine year-old girl, presenting
      with syncope caused by complete AV block. Despite intensive treatment, she died
      of multiple organ failure after two days. Infectious and congenital AV block were
      ruled out. Histology of the conduction system showed that a microscopic CTAVN was
      the cause of death. CTAVN is a rare cause of AV block and cardiac arrest, but
      should be considered in cases of unexplained death.

PMID- 22469166
TI  - [Signet ring cell carcinoma of the gallbladder].
AB  - Cancer in the gallbladder is rare, and each year about 160 cases are registered
      in Denmark. Most malignant tumours in the gallbladder are adenocarcinomas. We
      present a rare case of signet ring cell carcinoma of the gallbladder. Signet ring
      cell carcinomas are particularly aggressive. The tumours are often disseminated
      at the time of diagnosis, and it may be difficult to determine the primary
      origin.

PMID- 22469167
TI  - Place of residence before hospital admission and mortality at 12-months in
      Spanish patients aged 70 years or older.
AB  - AIM: Hospitalization of elderly people is often followed by high mortality rates.
      The aim of this study was to analyze the influence of prior residence on 1-year
      mortality after hospital discharge in patients aged 70 years and over. METHODS:
      This was a prospective observational cohort study. Participants were 426 patients
      discharged from the Internal Medicine Department at a Spanish Hospital who were
      followed for a 12-month period. Data collection was carried out during
      hospitalization and included sociodemographic characteristics, comorbidity
      (Charlson index), functional (Barthel index and Lawton scale) and cognitive
      conditions (Short Portable Mental Status Questionnaire), together with parameters
      related to the disease causing admission (diagnosis related group, laboratory
      tests, length of hospital stay). Mortality was carried out using telephone
      interviews. RESULTS: A total of 420 (98.6%) patients were located at the end of
      follow up. Of these, 95 patients had died, giving an overall 1-year mortality of
      22.6%. The mortality rate for patients living in their private homes was 15.6%
      versus 24.7% for those living with relatives and 60% for those living in
      institutions. After adjustment for potential confounders, prior residence was
      associated with mortality with a hazard ratio of 3.98 (95% CI 1.94-8.17) for
      those institutionalized and a hazard ration of 1.68 (95% CI 0.99-2.16) for those
      living with relatives, as compared with patients living in their private homes.
      CONCLUSIONS: Prior residence is associated with 1-year-mortality following
      discharge after controlling for several multidimensional factors.

PMID- 22469169
TI  - Heat generation during implant placement in low-density bone: effect of surgical
      technique, insertion torque and implant macro design.
AB  - OBJECTIVES: The study aimed to investigate the effect of surgical technique,
      implant macrodesign and insertion torque on bone temperature changes during
      implant placement. MATERIAL AND METHODS: In the in vitro study, 144 self-tapping
      (blueSKY((r)) 4 * 10 mm; Bredent) and 144 non-self-tapping (Standard implant((r))
      4.1 * 10 mm; Straumann) were placed in osteotomies prepared in pig ribs by
      lateral bone condensing or bone drilling techniques. The maximum insertion torque
      values of 30, 35 and 40 Ncm were used. Real-time bone temperature measurement
      during implant placement was performed by three thermocouples positioned
      vertically, in tripod configuration around every osteotomy, at a distance of 5 mm
      from it and at depths of 1, 5 and 10 mm. Data were analysed using Kruskal-Wallis,
      Mann-Whitney U-tests and Regression analysis. RESULTS: Significant predictor of
      bone temperature at the osteotomy depth of 1 mm was insertion torque (P = 0.003)
      and at the depth of 10-mm implant macrodesign (P = 0.029), while no significant
      predictor at depth of 5 mm was identified (P > 0.05). Higher insertion torque
      values as well as non-self-tapping implant macrodesign were related to higher
      temperatures. Implant placement in sites prepared by bone drilling induced
      significantly higher temperature increase (P = 0.021) compared with bone
      condensing sites at the depth of 5 mm, while no significant difference was
      recorded at other depths. Compared with 30 Ncm, insertion torque values of 35 and
      40 Ncm produced significantly higher temperature increase (P = 0.005; P = 0.003,
      respectively) at the depth of 1 mm. There was no significant difference in
      temperature change induced by 35 and 40 Ncm, neither by implant macrodesign at
      all investigated depths (P > 0.05). CONCLUSIONS: Placement of self-tapping
      implants with low insertion torque into sites prepared by lateral bone condensing
      technique might be advantageous in terms of thermal effect on bone.

PMID- 22469168
TI  - Partner randomized controlled trial: study protocol and coaching intervention.
AB  - BACKGROUND: Many children with asthma live with frequent symptoms and activity
      limitations, and visits for urgent care are common. Many pediatricians do not
      regularly meet with families to monitor asthma control, identify concerns or
      problems with management, or provide self-management education. Effective
      interventions to improve asthma care such as small group training and care
      redesign have been difficult to disseminate into office practice. METHODS AND
      DESIGN: This paper describes the protocol for a randomized controlled trial (RCT)
      to evaluate a 12-month telephone-coaching program designed to support primary
      care management of children with persistent asthma and subsequently to improve
      asthma control and disease-related quality of life and reduce urgent care events
      for asthma care. Randomization occurred at the practice level with eligible
      families within a practice having access to the coaching program or to usual
      care. The coaching intervention was based on the transtheoretical model of
      behavior change. Targeted behaviors included 1) effective use of controller
      medications, 2) effective use of rescue medications and 3) monitoring to ensure
      optimal control. Trained lay coaches provided parents with education and support
      for asthma care, tailoring the information provided and frequency of contact to
      the parent's readiness to change their child's day-to-day asthma management.
      Coaching calls varied in frequency from weekly to monthly. For each participating
      family, follow-up measurements were obtained at 12- and 24-months after
      enrollment in the study during a telephone interview. The primary outcomes were
      the mean change in 1) the child's asthma control score, 2) the parent's quality
      of life score, and 3) the number of urgent care events assessed at 12 and 24
      months. Secondary outcomes reflected adherence to guideline recommendations by
      the primary care pediatricians and included the proportion of children prescribed
      controller medications, having maintenance care visits at least twice a year, and
      an asthma action plan. Cost-effectiveness of the intervention was also measured.
      DISCUSSION: Twenty-two practices (66 physicians) were randomized (11 per
      treatment group), and 950 families with a child 3-12 years old with persistent
      asthma were enrolled. A description of the coaching intervention is presented.

PMID- 22469171
TI  - Chapter 1 creatine monohydrate.

PMID- 22469170
TI  - Clinical-scale isolation of interleukin-2-stimulated liver natural killer cells
      for treatment of liver transplantation with hepatocellular carcinoma.
AB  - Tumor recurrence is the main limitation of liver transplantation (LT) in patients
      with hepatocellular carcinoma (HCC) and can be promoted by immunosuppressants.
      However, there is no prevention or treatment for HCC recurrence after LT. Here we
      describe a clinical-scale method for an adoptive immunotherapy approach that uses
      natural killer (NK) cells derived from deceased donor liver graft perfusate to
      prevent tumor recurrence after LT. Liver mononuclear cells (LMNCs) that were
      extracted from deceased donor liver graft perfusate contained a high percentage
      of NK cells (45.0 +/- 4.0%) compared with peripheral blood mononuclear cells
      (PBMCs) (21.8 +/- 5.2%) from the same donor. The CD69 activation marker and the
      natural cytotoxicity receptors, NKp44 and NKp46, were expressed at high levels in
      freshly isolated liver NK cells. Furthermore, interleukin-2 (IL-2)-stimulated NK
      cells showed greater upregulation of activation markers and the tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL), which is critical for NK cell
      mediated antitumor cell death and increased production of interferon. Moreover,
      IL-2 stimulation induced LMNCs to exhibit a strong cytotoxicity against NK
      susceptible K562 target cells compared with PBMCs (p < 0.01). Finally, we also
      showed that the final product contained a very low T-cell contamination (0.02 +/-
      10(6) cells/kg(-1)), which reduces the risk of graft-versus-host disease (GVHD).
      Collectively, our results suggest that the adoptive transfer of IL-2-stimulated
      NK cells from deceased donor liver graft perfusate could be a promising treatment
      for LT patients with HCC.

PMID- 22469172
TI  - Chapter 2 cytarabine.

PMID- 22469173
TI  - Chapter 3 famotidine.

PMID- 22469175
TI  - Chapter 5 itraconazole: comprehensive profile.

PMID- 22469174
TI  - Chapter 4 fexofenadine hydrochloride.

PMID- 22469176
TI  - Chapter 6 ofloxacin.

PMID- 22469177
TI  - Chapter 7 Paclitaxel.

PMID- 22469178
TI  - Preface to volume 34.

PMID- 22469179
TI  - Activation of peroxisome proliferator-activated receptor gamma prolongs islet
      allograft survival.
AB  - Exposing donor mice to carbon monoxide (CO) protects transplanted islet
      allografts from immune rejection after transplantation (referred as the "donor"
      effect). In an attempt to understand the mechanisms of the donor effect of CO, we
      found that donor treatment with CO upregulates  expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma), a transcriptional regulator,
      in isolated islets. In this study, we evaluated whether PPARgamma contributes to
      the survival and function of transplanted islets and whether PPARgamma mediates
      the protective effect  of CO in a major mismatch islet allogeneic transplantation
      model. BALB/c (H-2(d)) islets in which PPARgamma activity was induced by its
      agonists, 15-deoxy-Delta(12-14)-prostaglandin J(2) (15d-PGJ(2)) or troglitazone
      were transplanted into C57BL/6 (H-2(b))  recipients that had been rendered
      diabetic by streptozotocin (STZ). Blood glucose levels of recipients were
      monitored to determine the function of transplanted islets. Our data indicated
      that PPARgamma activation in islets led to a high percentage of BALB/c islets
      survived long-term in C57BL/6  recipients. Activation of PPARgamma in the donor
      suppresses expressions of proinflammatory cytokines including tumor necrosis
      factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) in
      transplanted islets. Blocking PPARgamma activity by its antagonist, GW9662,
      abrogated the donor effect  of CO in vivo and in vitro. Our data demonstrate that
      PPARgamma plays a critical role in the survival and function of transplanted
      islets after transplantation in the recipient. The protective effects of CO are
      at least in part mediated by PPARgamma.

PMID- 22469180
TI  - Intermanual transfer of shapes in preterm human infants from 33 to 34 + 6 weeks
      postconceptional age.
AB  - This study investigated the ability of preterm infants to learn an object shape
      with one hand and discriminate a new shape in the opposite hand (without visual
      control). Twenty-four preterm infants between 33 and 34 + 6 gestational weeks
      received a tactile habituation task with either their right or left hand followed
      by a tactile discrimination task in the opposite hand. The results confirmed that
      habituation occurred for both shapes and both hands. Infants subsequently held
      the novel shape longer in the opposite hand. The results reveal that preterm
      infants are capable of intermanual transfer of shape information. In spite of the
      immaturity of the corpus callosum in preterm infants, its development seems to be
      sufficient to allow some transfer of information between both hands.

PMID- 22469181
TI  - Panton-Valentine leukocidin gene sequence variation and phage in methicillin
      resistant and methicillin-susceptible Staphylococcus aureus from children in
      mainland China.
AB  - To determine the variation in the Panton-Valentine leukocidin (PVL) gene
      sequences and different PVL-encoding phages of Staphylococcus aureus strains
      collected from children in mainland China, fifty-eight strains with PVL collected
      from 2007 to 2009 were used. Their molecular characteristics were examined.
      Primers were designed to sequence the PVL genes. Six PVL-encoding phages (phiPVL,
      phi108PVL, phiSLT, phiSa2MW, phiSa2958, and phiSa2USA) were identified by PCR.
      Eleven sequence types (ST) were detected with ST59 (39.7%, 23/58) the most
      frequent ST, followed by 910 (22.4%, 13/58), and 338 (12.1%, 7/58). Single
      nucleotide polymorphisms (SNP) were identified at 11 locations in the PVL genes.
      SNP (nucleotide 1396, A->G) and SNP (nucleotide 1546, A->G) were observed in >10
      sequences. Four additional SNP were non-synonymous. Both SNP (nucleotide 16, C
      >A) and SNP (nucleotide 62, C->T) were present in the same ST59 strain. SNP
      (nucleotide 527, A->G) was present in five strains belonging to ST30, 121, 1, and
      93. SNP (nucleotide 1436, A->C) was present in one ST30 strain. Fifteen strains
      belonging to ST910, ST217, and ST30 carried a PVL phage that had an icosahedral
      head morphology. Nine ST59 strains carried phi108PVL. Three ST88 strains carried
      a PVL phage that had an elongated head morphology. Twenty-seven strains,
      including 60.9% (14/23) of ST59 and all ST338 strains, had no detectable phage.
      In conclusion, sequence variation in PVL genes and PVL-encoding phages was
      generally related to the lineage. ST59 strains may indeed carry novel PVL phages.

PMID- 22469182
TI  - CO2 -dependent growth of Succinatimonas hippei YIT 12066T isolated from human
      feces.
AB  - Succinatimonas hippei is a new bacterial species isolated from human feces. Here
      we report that the growth of S. hippei YIT 12066(T) depends on CO(2) or
      bicarbonate and the headspace gas produced by microbiota. Genetic defect for
      carbonic anhydrase in this bacterium suggested a reason for the syntrophic
      property of CO(2) dependency and may suggest an adaptation to its habitat.

PMID- 22469183
TI  - Long-term effect of chronic intravenous and inhaled nephrotoxic antibiotic
      treatment on the renal function of patients with cystic fibrosis.
AB  - Cystic fibrosis (CF) patients have numerous infectious exacerbations requiring
      prolonged antibiotic treatments, some of which are nephrotoxic. Inhaled
      antibiotics can reach detectable serum levels. We studied the impact of chronic
      nephrotoxic antibiotic exposure on kidney function in CF population. We collected
      data retrospectively for 113 adult CF patients followed for 8.5 years. Fifty
      seven (50.4%) were males and 56 (49.5%) females (mean age 31.7 years [SD 9.9]),
      of which 31% had diabetes and 9.7% had hypertension. Over 8.5 years follow up,
      there were no significant changes in blood urea nitrogen (BUN; P = 0.92) or
      creatinine (P = 0.2) in the whole group. 22% of patients had >=1 episodes of
      acute kidney injury (AKI). The presence of AKI was associated with increased BUN
      (P = 0.002) and creatinine (P = 0.056) at the end of follow up. Use of
      intravenous colistin, gentamicin, tobramycin, or vancomycin did not correlate
      with increased BUN (P = 0.64; P = 0.49; P = 0.51; P = 0.47) or creatinine (P =
      0.43; P = 0.49; P = 0.17; P = 0.2) after 8.5 years. Elevated tobramycin peak and
      trough levels did not correlate with increased BUN or creatinine. Inhaled
      colistin and gentamicin correlated with increased BUN (P = 0.009; P = 0.02) but
      not creatinine (P = 0.45; P = 0.46). Inhaled tobramycin did not correlate with
      increased BUN (P = 0.17) or creatinine (P = 0.58). Only inhaled colistin
      correlated with AKI episodes (P = 0.03). Chronic inhaled colistin and gentamicin
      are associated with an increase in BUN but not creatinine at the end of follow
      up. Inhaled colistin was associated with episodes of AKI. Well-managed
      intravenous use of nephrotoxic antibiotics in CF population is associated with no
      major long-term renal toxicity.

PMID- 22469185
TI  - Meningoencephalitis complicating relapsing fever in traveler returning from
      Senegal.

PMID- 22469186
TI  - Intravascular ultrasound-assisted coronary sinus lead implant in patient with
      contrast anaphylaxis.
AB  - Ultrasound imaging has been used in a range of cardiac interventions. We describe
      the use of intravascular ultrasound to assist in coronary sinus lead implantation
      in a patient where contrast venography was contraindicated.

PMID- 22469187
TI  - Arecoline downregulates levels of p21 and p27 through the reactive oxygen
      species/mTOR complex 1 pathway and may contribute to oral squamous cell
      carcinoma.
AB  - Arecoline, the major alkaloid of areca nut, has been shown to cause strong
      genotoxicity and is considered a potential carcinogen. However, the detailed
      mechanism for arecoline-induced carcinogenesis remains obscure. In this study, we
      noticed that the levels of p21 and p27 increased in two oral squamous cell
      carcinoma cell lines with high confluence. Furthermore, when treated with
      arecoline, elevated levels of p21 and p27 could be downregulated through the
      reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway. Although arecoline
      decreased the activity of mTORC1, the amounts of autophagosome-like vacuoles or
      type II LC3 remained unchanged, suggesting that the downregulation of p21 and p27
      was independent of autophagy-mediated protein destruction. Arecoline also caused
      DNA damage through ROS, indicating that the reduced levels of p21 and p27 might
      facilitate G (1) /S transition of the cell cycle and subsequently lead to error
      prone DNA replication. In conclusion, these data have provided a possible
      mechanism for arecoline-induced carcinogenesis in subcytolytic doses in vivo.

PMID- 22469188
TI  - Body mass index (BMI) and dental caries in 5-year-old children from southern
      Sweden.
AB  - OBJECTIVES: The aim of the present survey was to study the association between
      dental caries and body mass index (BMI) in Swedish preschool children (born in
      1999). METHODS: A population-based and cross-sectional study design was used
      comprising all 920 5-year-old children in a defined area in and around the city
      of Lund. Anthropometric measures for the calculation of BMI were retrieved for
      each child from recordings at Child Health Care Centers (CHC). The occurrence of
      caries and fillings in the primary dentition, defined as deft (decayed,
      extracted, or filled primary teeth) and dt (decayed primary teeth), was collected
      from the children's dental records. RESULTS: The mean BMI was 16.1 (no
      differences between boys and girls). About 19.2% were overweight, of which 5.1%
      were obese. Overweight or obese children did not have higher deft or dt than
      others. However, children with low BMI (below -1 SD of national mean values for
      Swedish 5-year-olds) had statistically significantly higher deft and dt than
      children with normal BMI. CONCLUSIONS: Children with low BMI may be at risk of
      caries development. Low BMI may be associated with eating habits endangering
      dental health.

PMID- 22469189
TI  - Shared care: the barriers encountered by community-based palliative care teams in
      Ontario, Canada.
AB  - To meet the complex needs of patients requiring palliative care and to deliver
      holistic end-of-life care to patients and their families, an interprofessional
      team approach is recommended. Expert palliative care teams work to improve the
      quality of life of patients and families through pain and symptom management, and
      psychosocial spiritual and bereavement support. By establishing shared care
      models in the community setting, teams support primary healthcare providers such
      as family physicians and community nurses who often have little exposure to
      palliative care in their training. As a result, palliative care teams strive to
      improve not only the end-of-life experience of patients and families, but also
      the palliative care capacity of primary healthcare providers. The aim of this
      qualitative study was to explore the views and experiences of community-based
      palliative care team members and key-informants about the barriers involved using
      a shared care model to provide care in the community. A thematic analysis
      approach was used to analyse interviews with five community-based palliative care
      teams and six key-informants, which took place between December 2010 and March
      2011. Using the 3-I framework, this study explores the impacts of Institution
      related barriers (i.e. the healthcare system), Interest-related barriers (i.e.
      motivations of stakeholders) and Idea-related barriers (i.e. values of
      stakeholders and information/research), on community-based palliative care teams
      in Ontario, Canada. On the basis of the perspective of team members and key
      informants, it is suggested that palliative care teams experience sociopolitical
      barriers in an effort to establish shared care in the community setting. It is
      important to examine the barriers encountered by palliative care teams to address
      how to better develop and sustain them in the community.

PMID- 22469190
TI  - Emergency burr holes: "How to do it".
AB  - This paper describes a simple approach to emergency burr hole evacuation of extra
      axial intracranial haematoma that can be used in the uncommon situation when life
      saving specialist neurosurgical intervention is not available.

PMID- 22469191
TI  - Is Helicobacter pylori antibiotic resistance surveillance needed and how can it
      be delivered?
AB  - BACKGROUND: Most patients are prescribed Helicobacter pylori treatment without
      culture and antibiotic susceptibility testing, as current guidance recommends
      that patients with recurrent dyspepsia should be tested for H. pylori using a non
      invasive breath or faecal antigen test. AIMS: To determine the prevalence of H.
      pylori antibiotic resistance in patients attending endoscopy in England and
      Wales, and the feasibility of an antibiotic resistance surveillance programme
      testing. METHODS: We tested the antibiotic susceptibility of H. pylori isolates
      from biopsy specimens from 2063 of 7791 (26%) patients attending for endoscopy in
      Gloucester and Bangor, and 339 biopsy specimens sent to the Helicobacter
      Reference Unit (HRU) in London. Culture and susceptibility testing was undertaken
      in line with National and European methods. RESULTS: Helicobacter pylori were
      cultured in 6.4% of 2063 patients attending Gloucester and Bangor hospitals.
      Resistance to amoxicillin, tetracycline and rifampicin/rifabutin was below 3% at
      all centres. Clarithromycin, metronidazole and quinolone resistance was
      significantly higher in HRU (68%, 88%, 17%) and Bangor isolates (18%, 43%, 13%)
      than Gloucester (3%, 22%, 1%). Each previous course of these antibiotics is
      associated with an increase in the risk of antibiotic resistance to that agent
      [clarithromycin: RR = 1.5 (P = 0.12); metronidazole RR = 1.6 (P = 0.002);
      quinolone RR = 1.8 (P = 0.01)]. CONCLUSIONS: Helicobacter pylori infection is now
      uncommon in dyspeptic patients at endoscopy. A surveillance system is feasible
      and necessary to inform dyspepsia management guidance. Clinicians should take a
      thorough antibiotic history before prescribing metronidazole, clarithromycin or
      levofloxacin for H. pylori.

PMID- 22469192
TI  - Coccidioides posadasii infection in bats, Brazil.
AB  - To analyze the eco-epidemiologic aspects of Histoplasma capsulatum in Brazil, we
      tested 83 bats for this fungus. Although H. capsulatum was not isolated,
      Coccidioides posadasii was recovered from Carollia perspicillata bat lungs.
      Immunologic studies detected coccidioidal antibodies and antigens in Glossophaga
      soricina and Desmodus rotundus bats.

PMID- 22469193
TI  - Predicting the in-patient outcomes of acute medical admissions from the nursing
      home: the experience of St James's Hospital, Dublin, 2002-2010.
AB  - AIM: To identify predictors of negative in-patient outcomes (prolonged hospital
      stay and death) in nursing home (NH) residents admitted to the hospital as
      medical emergencies. METHODS: This was a retrospective patient series set at St
      James's Hospital (Dublin, Ireland). The participants were all NH patients
      requiring acute medical admission under the on-call medical team between 1
      January 2002 and 31 December 2010. Patient characteristics on admission, such as
      demographics, comorbidity level, major diagnostic categories, vital signs and
      laboratory profile, were measured. The outcomes of the study were prolonged
      hospital stay (>= 30 days) and in-hospital mortality. The characteristics of NH
      patients were compared with those of non-NH patients aged >= 65 years.
      Multivariate analyses were based on generalized estimating equations and
      classification trees. RESULTS: There were 55,763 acute medical admissions over
      the period, of which 1938 (3.5%) were from NH. As compared with non-NH patients
      aged >= 65 years, NH patients had greater acute illness severity. NH patients had
      a median length of stay of 7 days, and 17% had a prolonged admission. Their
      overall mortality rate was 23%. However, the classification analysis showed
      substantial patient heterogeneity; the subgroup with the highest mortality (54%,
      n = 100) had positive serum troponin and a respiratory major diagnosis. The
      lowest mortality rate (4%) was seen in those without positive troponin, urea of
      12 mmol/L or less, and albumin of more than 37 mg/L (n = 226). CONCLUSIONS:
      Simple serum markers, such as troponin, urea and albumin, might predict mortality
      in medically admitted NH patients. This might help health-care practitioners to
      anticipate their clinical course at an early stage.

PMID- 22469194
TI  - Diabetes, hepatitis virus infection and hepatocellular carcinoma: A case-control
      study in hepatitis endemic area.
AB  - AIM:   In spite of numerous studies on the association between diabetes mellitus
      (DM) and hepatocellular carcinoma (HCC), the results are inconsistent and whether
      and how the effect of DM on the risk for HCC is modified or synergistically
      exerted by hepatitis virus infection are still unclear. We aimed to elucidate and
      quantify the effect modification and synergism between hepatitis B and C virus
      (HBV and HCV, respectively) and DM leading to the risk for HCC and also assess
      the independent contribution of DM to the risk for HCC at population level
      (population attributable fraction) in a high prevalence area of hepatitis virus
      infection. METHODS:   A hospital-based case-control study was conducted from one
      medical center. Information on hepatitis B and C virus infection and DM status
      (defined by 8-h fasting blood glucose level >=126 mg/dL, current use of oral
      hyperglycemic agent or insulin injection) was collected to assess interaction of
      hepatitis virus infection with DM on the risk for HCC. RESULTS:   The association
      between DM and the risk for HCC was significant regardless of the presence of HBV
      infection, whereas a significant positive association was noted for HCV
      negativity. Synergistic interactions between DM and HBV infection were
      significant. In the absence of both hepatitis virus infections, the independent
      effect of DM accounted for 7.5% risk for HCC from the underlying population.
      CONCLUSION:   The effect of DM on the risk for developing HCC is higher in HCV
      negative patients and synergistic with HBV infection. The independent effect of
      DM provides a new insight to the prevention of HCC other than virus-related
      mechanism.

PMID- 22469195
TI  - Lessons learned during dengue outbreaks in the United States, 2001-2011.
AB  - Since 2001, three autochthonous dengue fever outbreaks have occurred in the
      United States: in Hawaii (2001); Brownsville, Texas (2005); and southern Florida
      (2009-2011). We sought to characterize and describe the response to these
      outbreaks from the perspectives of public health and vector control officials. By
      conducting a medical literature review through PubMed and news media searches
      through Google, we identified persons involved in managing each outbreak; 26
      persons then participated in qualitative, semistructured interviews. After
      analyzing the 3 outbreaks, we found the following prominent themes in the
      response efforts: timely detection of illness; communication of up-to-date,
      correct information; and development of a rapid response that engages the
      community. We therefore recommend that public health authorities involve the
      clinical and laboratory community promptly, provide accurate information, and
      engage the local community in vector control and case identification and
      reporting.

PMID- 22469196
TI  - Long-term retrospective study of narrow implants for fixed dental prostheses.
AB  - OBJECTIVE: The objectives of this study were to analyze retrospectively the long
      term survival and success rates of Narrow implants (NIs) placed with various
      implant systems, and the association with biological and technical complications.
      MATERIAL AND METHODS: In total, 338 patients (men = 45.6%, women = 54.4%) who
      received 541 NIs (<=3.5 mm in diameter) for fixed prostheses were enrolled in
      this retrospective study. The mean marginal bone level (MMBL) change was
      calculated. Life table analysis with the cumulative survival rate and success
      rate was calculated, and biological and technical complications were evaluated.
      RESULTS: The annual MMBL change was 0.07 +/- 0.20 mm. The 12-year cumulative
      survival (success) rates of NIs were 98.1% (91.8%) and 98.5% (93.8%) for the
      implant- and subject-based analysis, respectively. During the observation period
      up to 12 years (mean 4.9 years), six implants were lost in the maxilla, whereas
      three implants were lost in the mandible. Technical complications were more
      frequent than biological complications. Infection was the most common underlying
      cause of biological complications and the most frequent technical complication
      was decementation. CONCLUSION: In conclusion, the findings of this study suggest
      that NIs could be used safely for narrow alveolar ridges or narrow mesiodistal
      spaces on the basis of their high survival rate.

PMID- 22469197
TI  - Duration and compliance with antidepressant treatment in immigrant and native
      born populations in Spain: a four year follow-up descriptive study.
AB  - BACKGROUND: Non-compliance with antidepressant treatment continues to be a
      complex problem in mental health care. In immigrant populations non-compliance is
      one of several barriers to adequate management of mental illness; some data
      suggest greater difficulties in adhering to pharmacological treatment in these
      groups and an increased risk of therapeutic failure. The aim of this study is to
      assess differences in the duration and compliance with antidepressant treatment
      among immigrants and natives in a Spanish health region. METHODS: Population
      based (n = 206,603), retrospective cohort study including all subjects prescribed
      ADT between 2007 and 2009 and recorded in the national pharmacy claims database.
      Compliance was considered adequate when the duration was longer than 4 months and
      when patients withdrew more than 80% of the packs required. RESULTS: 5334
      subjects (8.5% of them being immigrants) initiated ADT. Half of the immigrants
      abandoned treatment during the second month (median for natives = 3 months). Of
      the immigrants who continued, only 29.5% presented good compliance (compared with
      38.8% in natives). The estimated risk of abandoning/ending treatment in the
      immigrant group compared with the native group, adjusted for age and sex, was
      1.28 (95%CI 1.16-1.42). CONCLUSIONS: In the region under study, immigrants of all
      origins present higher percentages of early discontinuation of ADT and lower
      median treatment durations than the native population. Although this is a
      complex, multifactor situation, the finding of differences between natives and
      immigrants in the same region suggests the need to investigate the causes in
      greater depth and to introduce new strategies and interventions in this
      population group.

PMID- 22469198
TI  - Identification of factors affecting tacrolimus level and 5-year clinical outcome
      in kidney transplant patients.
AB  - The purpose of this study was to identify and characterize the association of
      various clinical variables and CYP3A5 genotypes with the pharmacokinetics of
      tacrolimus and outcome over 1-5 years in kidney transplantation patients in
      Korea. A total of 129 recipients (aged 18-65 years) administered tacrolimus were
      genotyped for CYP3A5 (6986A>G in intron 3; rs776746). Clinical covariates and
      trough levels, doses and dose-adjusted trough levels of tacrolimus, as well as
      complications during the 1-5 years after transplantation, were analysed. A linear
      mixed model was used to investigate potential factors affecting the trough
      levels, doses and dose-adjusted levels of tacrolimus. We identified factors
      affecting chronic allograft nephropathy (CAN) and tacrolimus-related
      complications. After adjusting for sex, body-weight and doses of corticosteroids
      and mycophenolate mofetil, we noted that CYP3A5 genotypes had the most profound
      effect on the dose and dose-adjusted trough levels of tacrolimus 1-5 years after
      transplantation (p < 0.001). Trough levels of tacrolimus were associated with
      post-transplantation hyperlipidaemia (p < 0.05), and estimated glomerular
      filtration rate was associated with CAN (p < 0.05). Therefore, the CYP3A5
      genotype is a variable marker for tacrolimus dose requirement, and the trough
      level of tacrolimus should be controlled to minimize post-transplant
      hyperlipidaemia to achieve optimum outcome.

PMID- 22469199
TI  - Evaluation of the Daphnia magna reproduction test for detecting endocrine
      disruptors.
AB  - The Daphnia 21 d reproduction test is considered as a comprehensive and decisive
      test in the OECD Conceptual Framework for testing and assessment of endocrine
      disrupting chemicals (EDCs). However, how to interpret results of the Daphnia 21
      d reproduction test for identification, risk assessment and testing strategy of
      EDCs remains an unsolved issue. This study analysed a total number of 135
      published studies encompassing 86 known EDCs and non-EDCs with different modes of
      action. Our results show that the majority of effects on apical endpoints
      (survival, molting, growth, time to reproductive maturity, brood size, the number
      of broods, and the total number of offspring) do not seem to be EDC-specific. In
      contrast, the endpoint sex ratio is likely specific to juvenile hormones and
      their mimics. Variability is quantified for three most reported endpoints
      survival, the total number of offspring and sex ratio. Quantification of the
      endpoint sensitivity shows that the sensitivity of the sex ratio is lower than
      that of the total number of offspring. The Daphnia 21 d reproduction test gives
      insufficient information to conclude if a substance is an EDC or not. EDCs that
      are potent in assays in vitro may not be potent in the Daphnia 21 d reproduction
      test. We conclude that the Daphnia 21 d reproduction test is important for
      deriving No Observed Effect Concentrations for risk assessment but may produce
      false negatives in identification of EDCs when used on its own. A targeted
      testing strategy for selection of species, tests, and endpoints is suggested for
      identifying EDCs.

PMID- 22469200
TI  - Depression and nonadherence predict mortality in hemodialysis treated end-stage
      renal disease patients.
AB  - The scientific evaluation of depression's impact on mortality in hemodialysis
      (HD) patients has yielded mixed results, with the more recent, more rigorous
      studies detecting a significant relationship. In this study, 130 HD patients from
      an urban North American hospital were evaluated for depressive affect and then
      observed for up to 5 years. In a corrected Cox regression model, which held
      constant age, gender, dialysis vintage, illness severity and diabetic status,
      depressive affect emerged as a modest but significant predictor of mortality
      (relative risk = 1.05, 95% confidence interval = 1.01-1.08). When the subjects
      were divided according to depressive affect severity, those with severe
      depressive affect had significantly shorter time to death (beta = 0.452, P =
      0.044). In a subgroup of 85 subjects, self-reported medication adherence was also
      predictive of mortality, with higher rates of nonadherence being associated with
      increased mortality risk. This paper lends support to the burgeoning literature
      on depression and reduced survival in HD populations, as well as begins the
      investigation of understanding the underlying mechanisms.

PMID- 22469201
TI  - Introduction.

PMID- 22469202
TI  - Emerging trends and treatment approaches in nonmelanoma skin cancer : a Canadian
      perspective.

PMID- 22469203
TI  - Melanoma in 2011.

PMID- 22469204
TI  - Photoaging: a review of current concepts of pathogenesis.

PMID- 22469205
TI  - Indoor tanning devices.

PMID- 22469206
TI  - Sunscreen and sun protection: shedding light on recent advances.

PMID- 22469207
TI  - Community programs in reducing ultraviolet radiation exposure.

PMID- 22469208
TI  - Potential antitumor applications of a monoclonal antibody specifically targeting
      human papilloma virus 16 E7 49-57 peptide.
AB  - Our study aims to evaluate whether the approach of TCRm mAb has therapeutic
      potential against HPV-induced tumors. In the present study, we generated a murine
      IgG2a mAb 6C10 specifically recognizing HPV-16-E7(49-57)  epitope (RAHYNIVTF) in
      the polypeptides and in complex with a MHC class I molecule. Analysis of the
      primary structure shows that the 6C10 Ab displays a novel sequence in the CDR of
      the heavy chain, compared to the sequences in the Kabat database, which suggests
      the Ab has completed its affinity maturation. The 6C10 Ab can specifically
      recognize E7 and Trx-E7(30-67)  protein in ELISA, and can also specifically bind
      to T2 cell carrying HPV-16-E7(49-57)  peptide. In the TC-1 cell tumor-bearing
      mouse model, 6C10 exhibits tumor suppression activity when compared to the
      isotype control Ab. 6C10 Ab has showed tumor-inhibition potency in a mouse model
      and this Ab may have the prospect of cancer therapy.

PMID- 22469209
TI  - Longitudinal antecedents of executive function in preschoolers.
AB  - Despite an extensive history underscoring the role of social processes and child
      contributions to the development of executive functions (C. Lewis & J.
      Carpendale, 2009; L. S. Vygotsky, 1987), research on these relations is sparse.
      To address this gap, 68 mother-child dyads were examined to determine whether
      maternal attention-directing behaviors (attention maintaining, attention
      redirection) and toddlers' temperament predicted executive processes during
      preschool (mean age = 4.5 years, SD = 0.46)-delay and conflict inhibition.
      Maternal attention maintaining was associated with high levels of conflict
      inhibition for inhibited and exuberant children, whereas attention redirection
      was associated with low levels of delay and conflict inhibition for inhibited
      children. Therefore, maternal attention-directing behaviors may enhance the
      development of executive functions but only for children with inhibited and
      exuberant temperaments.

PMID- 22469211
TI  - A national epidemiological study of Myasthenia Gravis in Australia.
AB  - BACKGROUND AND PURPOSE: Existing epidemiological studies of Myasthenia Gravis
      have generally examined small populations. Few national studies have been
      conducted, and published incidence and prevalence rates vary widely. We report
      one of the largest national studies of Myasthenia Gravis, and the first incidence
      and prevalence rates for Australia. METHODS: Prescriptions for Pyridostigmine
      Bromide in 2009 were utilized from a national prescribing database to estimate
      incidence and the prevalence of symptomatic and treated disease. Crude rates were
      age-standardized to the WHO world population. We compared standardized rates to
      recent national studies from Norway and Taiwan. RESULTS: In 2009, there were 2574
      prevalent cases of symptomatic and treated Myasthenia Gravis, corresponding to an
      annual crude prevalence rate of 117.1 per 1 million residents. There were 545
      incident cases, yielding a crude incidence rate of 24.9 per 1 million residents.
      The crude incidence in women and men was estimated to be 27.9 and 21.9 per 1
      million, respectively. Prevalence and incidence rates were higher in women than
      men between the ages of 15 and 64 years, and were higher in men than women in
      those older than 65 years. Rates peaked between the ages of 74 and 84 years,
      declining thereafter. Standardized incidence was higher in Australia than Norway,
      but similar to Taiwan (P-values = 0.007 and 1.00, respectively). CONCLUSIONS:
      This first Australian epidemiological study of symptomatic Myasthenia Gravis is
      one of the largest population-based studies ever reported and supports higher
      incidence rates for Myasthenia Gravis. Myasthenia Gravis disproportionately
      affected younger females and older males.

PMID- 22469212
TI  - [Research in primary care as knowledge area].

PMID- 22469213
TI  - [Access to diagnostic technology by Primary Care doctors].

PMID- 22469214
TI  - In vitro comparison of fracture strength of experimental hollow and solid design
      zirconia dowels.
AB  - PURPOSE: The aim of this study was to evaluate the fracture strength of
      experimental hollow and solid design zirconia dowels. MATERIALS AND METHODS:
      Three types of dowels (fiber-reinforced composite [FRC], hollow design, and solid
      design zirconia dowels) were tested in the study (n = 10). A three-point bending
      method was conducted, and a load was applied until fracture. The values were
      recorded as Newtons (N) and then converted to megapascals (MPa) according to the
      diameter of the dowels. Statistical analyses were performed using one-way ANOVA
      and Tukey HSD tests. The significance was set at p < 0.05. RESULTS: The mean
      fracture strength of the hollow design zirconia dowels was significantly higher
      (960.72 MPa) than solid zirconia dowels (741.78 MPa) and FRC dowels (687.64 MPa)
      (p < 0.05). CONCLUSIONS: The hollow design zirconia dowel seems to have
      sufficient fracture strength for anterior restorations. This design may be
      beneficial to access the apical region when retreatment is necessary, without any
      dowel-removing procedure.

PMID- 22469215
TI  - Electrical isolation of both left pulmonary veins by a single left atrial
      endocardial radiofrequency energy application: ablation of marshall bundle
      bypass.
AB  - The muscular sleeve contained within the ligament of Marshall (Marshall Bundle,
      MB) has been implicated in triggering and/or maintaining atrial fibrillation. Its
      connections may form a conduit between the left atrium (LA) and the left
      pulmonary veins (PVs) and challenge PV isolation attempts. In this case,
      radiofrequency (RF) ablation at antra of both left PVs failed to affect venous
      electrical activity. However, isolation of both PVs occurred simultaneously with
      a single, short (14 seconds) RF energy application at the mitral isthmus. This
      was delivered at a site recording a complex continuous electrogram (duration 100
      ms), interpreted as the site of a single connection between LA and MB.

PMID- 22469217
TI  - Serologic evidence of orthopoxvirus infection in buffaloes, Brazil.

PMID- 22469218
TI  - Benchmark dose analysis for Bacillus anthracis inhalation exposures in the
      nonhuman primate.
AB  - There is considerable variability in the published lethality values for
      inhalation exposures of Bacillus anthracis. The lack of consensus on an
      acceptable dose-response relationship poses a significant challenge in the
      development of risk-based management approaches for use following a terrorist
      release of B. anthracis spores. This article reviewed available B. anthracis dose
      response modeling and literature for the nonhuman primate, evaluated the use of
      the U.S. Environmental Protection Agency's Benchmark Dose Software (BMDS) to fit
      mathematical dose-response models to these data, and reported results of the
      benchmark dose analysis of suitable data sets. The BMDS was found to be a useful
      tool to evaluate dose-response relationships in microbial data, including that
      from B. anthracis exposure. An evaluation of the sources of variability
      identified in the published lethality data and the corresponding BMDS-derived
      lethality values found that varying levels of physical characterization of the
      spore product, differing receptor-specific exposure assumptions, choice of dose
      metrics, and the selected statistical methods all contributed to differences in
      lethality estimates. Recognition of these contributors to variability could
      ultimately facilitate agreement on a B. anthracis dose-response relationship
      through provision of a common description of necessary study considerations for
      acceptable dose-response data sets.

PMID- 22469219
TI  - Atorvastatin calcium.

PMID- 22469221
TI  - Donepezil.

PMID- 22469220
TI  - Clopidogrel bisulfate.

PMID- 22469222
TI  - Omeprazole.

PMID- 22469223
TI  - Parbendazole.

PMID- 22469224
TI  - Rocuronium bromide.

PMID- 22469225
TI  - Vigabatrin.

PMID- 22469226
TI  - Zaleplon.

PMID- 22469227
TI  - Cocrystal systems of pharmaceutical interest: 2007-2008.

PMID- 22469228
TI  - Preface to volume 35.

PMID- 22469229
TI  - cAMP response element-binding protein 1 is required for hydroxyurea-mediated
      induction of gamma-globin expression in K562 cells.
AB  - 1. Hydroxyurea (HU) is a drug used for the treatment of haemoglobinopathies.
      Hydroxyurea functions by upregulating gamma-globin transcription and fetal
      haemoglobin (HbF) production in erythroid cells. The K562 erythroleukaemia cell
      line is widely used as a model system in which to study the mechanism of gamma
      globin induction by HU. However, the transcription factors required for the
      upregulation of gamma-globin expression by HU in K562 cells have not been
      identified. Similarities between the HU and sodium butyrate (SB) pathways suggest
      cAMP response element-binding protein (CREB) 1 as a potential candidate. Thus,
      the aim of the present study was to investigate the possible role of CREB1 in the
      HU pathway. 2. Experiments were performed using transient and stable RNA
      interference (RNAi) to show that CREB1 is necessary for HU-mediated induction of
      gamma-globin expression and haemoglobin production in K562 cells. 3. Furthermore,
      western blot analyses demonstrated that CREB1 becomes phosphorylated in a dose
      dependent manner after HU (100-400 umol/L) treatment of K562 cells for 72 h. 4.
      We also investigated role of a Ggamma promoter CREB1 response element (G-CRE) in
      this pathway. Quantitative amplification refractory mutation system-polymerase
      chain reaction experiments were performed to demonstrate that HU induces the
      expression of both Ggamma and Agamma in this cell line. In addition,
      electrophoretic mobility shift assays were used to show that levels of CREB1
      complexes binding to the G-CRE site are increased following HU treatment and are
      decreased in CREB1-knockdown cells. 5. The results suggest that CREB1 is
      necessary for gamma-globin induction by HU in K562 cells, a role that may be
      mediated, in part, through the G-CRE element.

PMID- 22469230
TI  - Surveillance for West Nile, dengue, and chikungunya virus infections, Veneto
      Region, Italy, 2010.
AB  - In 2010, in Veneto Region, Italy, surveillance of summer fevers was conducted to
      promptly identify autochthonous cases of West Nile fever and increase detection
      of imported dengue and chikungunya in travelers. Surveillance highlighted the
      need to modify case definitions, train physicians, and when a case is identified,
      implement vector control measures.

PMID- 22469232
TI  - Interactive virtual reality Wii in geriatric day hospital: a study to assess its
      feasibility, acceptability and efficacy.
AB  - AIM: Rehabilitation using interactive virtual reality Wii (Wii-IVR) was shown to
      be feasible in patients with different medical problems, but there was no study
      examining its use in a geriatric day hospital (GDH). The aim of the present study
      was to test the feasibility, acceptability and efficacy of Wii-IVR in GDH.
      METHODS: It was a clinical trial with matched historic controls. Patients of a
      GDH were recruited to participate in Wii-IVR by playing "Wii Fit". Participants
      used a Wii controller to carry out movements involved in an arm ergometer. Each
      participant received eight sessions of Wii-IVR in addition to conventional GDH
      rehabilitation. Feasibility was assessed by the total time receiving Wii-IVR, the
      percentage of maximal heart rate reserve (%MHR) and Borg perceived exertion scale
      (BS) after participating in Wii-IVR. %MHR and BS were compared with those after
      carrying out an arm ergometer for the same duration. Acceptability was assessed
      by an interviewer-administered questionnaire. Efficacy was assessed by comparing
      improvements in Functional Independence Measure (FIM) between participants and
      matched historic controls, who received conventional GDH rehabilitations only.
      RESULTS: A total of 30 patients completed the study. Participants completed a
      total of 1941 min of event-free Wii-IVR. The mean %MHR was 15.9% +/- 9.9% and the
      mean BS was 7.9 +/- 2.3. There was no significant difference in %MHR and BS
      between participating in Wii-IVR and arm ergometer. Most participants found Wii
      IVR similar to the arm ergometer, and would like to continue Wii-IVR if they had
      Wii at home. Improvements in FIM of participants were significantly more than
      that of historic controls. CONCLUSIONS: Wii-IVR in GDH was feasible and most
      participants accepted it. Participants had more improvements in FIM.

PMID- 22469233
TI  - Focus on designing health care structures and services for rare diseases.

PMID- 22469234
TI  - Malaria in highlands of Ecuador since 1900.
AB  - A recent epidemic of malaria in the highlands of Bolivia and establishment of
      multiple Anopheles species mosquitoes in the highlands of Ecuador highlights the
      reemergence of malaria in the Andes Mountains in South America. Because malaria
      was endemic to many highland valleys at the beginning of the 20th century, this
      review outlines the 20th century history of malaria in the highlands of Ecuador,
      and focuses on its incidence (e.g., geographic distribution) and elimination from
      the northern highland valleys of Pichincha and Imbabura and the role of the
      Guayaquil to Quito railway in creating highland larval habitat and inadvertently
      promoting transportation of the vector and parasite. Involvement of control
      organizations in combating malaria in Ecuador is also outlined in a historical
      context.

PMID- 22469236
TI  - The JAK2 V617F mutation in patients with cerebral venous thrombosis.
AB  - BACKGROUND: It is currently unclear whether or not cerebral venous thrombosis,
      such as splanchnic venous thrombosis, can be the first manifestation of an
      underlying myeloproliferative neoplasm. OBJECTIVE: To determine the prevalence of
      the JAK2 V617F mutation in patients with a first episode of cerebral venous
      thrombosis. PATIENTS: In this retrospective cohort study, patients with cerebral
      venous thrombosis were tested for the JAK2 V617F mutation and were followed until
      the development of a myeloproliferative neoplasm or censored at the end of follow
      up. RESULTS: Ten of 152 patients (6.6%) carried the JAK2 V617F mutation. Three of
      them had known acquired risk factors for thrombosis, and five had thrombophilia.
      Six patients met the diagnostic criteria for myeloproliferative neoplasm at the
      time of cerebral venous thrombosis, and three additional patients developed the
      disease during the follow-up (median duration 7.8 years, range 6 months to 21.3
      years), giving an annual incidence of 0.26% patient-years (95% confidence
      interval 0.05-0.64). The last patient has no evidence of disease after 3 years of
      follow-up. Patients without the JAK2 V617F mutation at the time of cerebral
      venous thrombosis were retested at the end of the follow-up and remained
      negative, with normal blood counts (log-rank test chi(2) : 159 [P<0.0001]).
      CONCLUSIONS: Cerebral venous thrombosis can be the first symptom of a
      myeloproliferative neoplasm. Patients with cerebral venous thrombosis can carry
      the JAK2 V617F mutation, irrespective of blood count.

PMID- 22469235
TI  - Predictors of binge drinking in adolescents: ultimate and distal factors - a
      representative study.
AB  - BACKGROUND: As epidemiological surveys have shown, binge drinking is a constant
      and wide-spread problem behavior in adolescents. It is not rare to find that more
      than half of all adolescents engage in this behavior when assessing only the last
      4 weeks of time independent of the urbanity of the region they live in. There
      have been several reviews on predictors of substance consumption in adolescents
      in general, but there has been less high quality research on predictors of binge
      drinking, and most studies have not been theoretically based. The current study
      aimed to analyze the ultimate and distal factors predicting substance consumption
      according to Petraitis' theory of triadic influence. We assessed the predictive
      value of these factors with respect to binge drinking in German adolescents,
      including the identification of influence direction. METHODS: In the years
      2007/2008, a representative written survey of N = 44,610 students in the 9th
      grade of different school types in Germany was carried out (net sample). The
      return rate of questionnaires was 88% regarding all students whose teachers or
      school directors had agreed to participate in the study. In this survey,
      prevalence of binge drinking was investigated as well as potential predictors
      from the social/interpersonal, the attitudinal/environmental, and the
      intrapersonal fields (3 factors of Petraitis). In a multivariate logistic
      regression analysis, these variables were included after testing for
      multicollinearity in order to assess their ability to predict binge drinking.
      RESULTS: Prevalence of binge drinking in the last 30 days was 52.3% for the
      surveyed adolescents with a higher prevalence for boys (56.9%) than for girls
      (47.5%). The two most influential factors found to protect against binge drinking
      with p < .001 were low economic status and importance of religion. The four most
      relevant risk factors for binge drinking (p < .001) were life-time prevalence of
      school absenteeism/truancy, academic failure, suicidal thoughts, and violence at
      school in the form of aggressive behavior of teachers. The model of Petraitis was
      partly confirmed for Binge Drinking in German adolescents and the direction of
      influence factors was clarified. CONCLUSIONS: Whereas some of the risk and
      protective factors for binge drinking are not surprising since they are known for
      substance abuse in general, there are two points that could be targeted in
      interventions that do not focus on adolescents alone: (a) training teachers in
      positive, reassuring behavior and constructive criticism and (b) a focus on high
      risk adolescents either because they have a lack of coping strategies when in a
      negative mood or because of their low academic achievement in combination with
      absenteeism from school.

PMID- 22469237
TI  - Novel positron emission tomography/computed tomography of diffuse parenchymal
      lung disease combining a labeled somatostatin receptor analogue and 2-deoxy
      2[18F]fluoro-D-glucose.
AB  - We prospectively investigated the potential of positron emission tomography (PET)
      using the somatostatin receptor (SSTR) analogue 68Ga-DOTATATE and 2-deoxy
      2[18F]fluoro-D-glucose (18F-FDG) in diffuse parenchymal lung disease (DPLD).
      Twenty-six patients (mean age 68.9 +/- 11.0 years) with DPLD were recruited for
      68Ga-DOTATATE and 18F-FDG combined PET/high-resolution computed tomography (HRCT)
      studies. Ten patients had idiopathic pulmonary fibrosis (IPF), 12 patients had
      nonspecific interstitial pneumonia (NSIP), and 4 patients had other forms of
      DPLD. Using PET, the pulmonary tracer uptake (maximum standardized uptake value
      [SUV(max)]) was calculated. The distribution of PET tracer was compared to the
      distribution of lung parenchymal changes on HRCT. All patients demonstrated
      increased pulmonary PET signal with 68Ga-DOTATATE and 18F-FDG. The distribution
      of parenchymal uptake was similar, with both tracers corresponding to the
      distribution of HRCT changes. The mean SUV(max) was 2.2 +/- 0.7 for 68Ga-DOTATATE
      and 2.8 +/- 1.0 (t-test, p  =  .018) for 18F-FDG. The mean 68Ga-DOTATATE SUV(max)
      in IPF patients was 2.5 +/- 0.9, whereas it was 2.0 +/- 0.7 (p  =  .235) in NSIP
      patients. The correlation between 68Ga-DOTATATE SUV(max) and gas transfer
      (transfer factor of the lung for carbon monoxide [TLCO]) was r  =  -.34 (p  = 
      .127) and r  =  -.49 (p  =  .028) between 18F-FDG SUV(max) and TLCO. We provide
      noninvasive in vivo evidence in humans showing that SSTRs may be detected in the
      lungs of patients with DPLD in a similar distribution to sites of increased
      uptake of 18F-FDG on PET.

PMID- 22469238
TI  - Comparative study of the optical and heat generation properties of IR820 and
      indocyanine green.
AB  - AbstractNear-infrared (NIR) fluorophores are the focus of extensive research for
      combined molecular imaging and hyperthermia. In this study, we showed that the
      cyanine dye IR820 has optical and thermal generation properties similar to those
      of indocyanine green (ICG) but with improved in vitro and in vivo stability. The
      fluorescent emission of IR820 has a lower quantum yield than ICG but less
      dependence of the emission peak location on concentration. IR820 demonstrated
      degradation half-times approximately double those of ICG under all temperature
      and light conditions in aqueous solution. In hyperthermia applications, IR820
      generated lower peak temperatures than ICG (4-9%) after 3-minute laser exposure.
      However, there was no significant difference in hyperthermia cytotoxicity, with
      both dyes causing significant cell growth inhibition at concentrations >= 5 MUM.
      Fluorescent images of cells with 10 MUM IR820 were similar to ICG images. In
      rats, IR820 resulted in a significantly more intense fluorescence signal and
      significantly higher organ dye content than for ICG 24 hours after intravenous
      dye administration (p < .05). Our study shows that IR820 is a feasible agent in
      experimental models of imaging and hyperthermia and could be an alternative to
      ICG when greater stability, longer image collection times, or more predictable
      peak locations are desirable.

PMID- 22469239
TI  - Monoclonal antibodies conjugated with superparamagnetic iron oxide particles
      allow magnetic resonance imaging detection of lymphocytes in the mouse brain.
AB  - We investigated the potential of antibody-vectorialized superparamagnetic iron
      oxide (SPIO) particles as cellular specific magnetic resonance contrast agents to
      image lymphocyte populations within the central nervous system (CNS), with the
      final goal of obtaining a reliable tool for noninvasively detecting and tracking
      specific cellular populations in vivo. We used superparamagnetic particles bound
      to a monoclonal antibody. The particle is the contrast agent, by means of its T2*
      relaxation properties; the antibody is the targeting vector, responsible for
      homing the particle to target a surface antigen. To investigate the efficiency of
      particle vectorialization by these antibodies, we compared two types of antibody
      vectorialized CD3-specific particles in vivo. We successfully employed
      vectorialized SPIO particles to image B220+ cells in a murine model of B-cell
      lymphoma. Likewise, we were able to identify CD3+ infiltrates in a murine model
      of multiple sclerosis. The specificity of the technique was confirmed by
      immunohistochemistry and electron microscopy of corresponding sections. Our
      findings suggest that indirect binding of the antibody to a streptavidinated
      particle allows for enhanced particle vectorialization compared to covalent
      binding of the antibody to the particle.

PMID- 22469240
TI  - Bioluminescence and magnetic resonance imaging of macrophage homing to
      experimental abdominal aortic aneurysms.
AB  - Macrophage infiltration is a prominent feature of abdominal aortic aneurysm (AAA)
      progression. We used a combined imaging approach with bioluminescence (BLI) and
      magnetic resonance imaging (MRI) to study macrophage homing and accumulation in
      experimental AAA disease. Murine AAAs were created via intra-aortic infusion of
      porcine pancreatic elastase. Mice were imaged over 14 days after injection of
      prepared peritoneal macrophages. For BLI, macrophages were from transgenic mice
      expressing luciferase. For MRI, macrophages were labeled with iron oxide
      particles. Macrophage accumulation during aneurysm progression was observed by in
      situ BLI and by in vivo 7T MRI. Mice were sacrificed after imaging for histologic
      analysis. In situ BLI (n  =  32) demonstrated high signal in the AAA by days 7
      and 14, which correlated significantly with macrophage number and aortic
      diameter. In vivo 7T MRI (n  =  13) at day 14 demonstrated T2* signal loss in the
      AAA and not in sham mice. Immunohistochemistry and Prussian blue staining
      confirmed the presence of injected macrophages in the AAA. BLI and MRI provide
      complementary approaches to track macrophage homing and accumulation in
      experimental AAAs. Similar dual imaging strategies may aid the study of AAA
      biology and the evaluation of novel therapies.

PMID- 22469241
TI  - Single-photon emission computed tomographic imaging of the early time course of
      therapy-induced cell death using technetium 99m tricarbonyl His-annexin A5 in a
      colorectal cancer xenograft model.
AB  - As apoptosis occurs over an interval of time after administration of apoptosis
      inducing therapy in tumors, the changes in technetium 99m ((99m)Tc)-tricarbonyl
      (CO)3 His-annexin A5 (His-ann A5) accumulation over time were examined. Colo205
      bearing mice were divided into six treatment groups: (1) control, (2) 5
      fluorouracil (5-FU; 250 mg/kg), (3) irinotecan (100 mg/kg), (4) oxaliplatin (30
      mg/kg), (5) bevacizumab (5 mg/kg), and (6) panitumumab (6 mg/kg). (99m)Tc-(CO)3
      His-ann A5 was injected 4, 8, 12, 24, and 48 hours posttreatment, and micro
      single-photon emission computed tomography was performed. Immunostaining of
      caspase-3 (apoptosis), survivin (antiapoptosis), and LC3-II (autophagy marker)
      was also performed. Different dynamics of (99m)Tc-(CO)3 His-ann A5 uptake were
      observed in this colorectal cancer xenograft model, in response to a single dose
      of three different chemotherapeutics (5-FU, irinotecan, and oxaliplatin).
      Bevacizumab-treated mice showed no increased uptake of the radiotracer, and a
      peak of (99m)Tc-(CO)3 His-ann A5 uptake in panitumumab-treated mice was observed
      24 hours posttreatment, as confirmed by caspase-3 immunostaining. For irinotecan
      , oxaliplatin-, and bevacizumab-treated tumors, a significant correlation was
      established between the radiotracer uptake and caspase-3 immunostaining (r  = 
      .8, p < .05; r  =  .9, p < .001; r  =  .9, p < .001, respectively). For 5-FU- and
      panitumumab-treated mice, the correlation coefficients were r  =  .7 (p  =  .18)
      and r  =  .7 (p  =  .19), respectively. Optimal timing of annexin A5 imaging
      after the start of different treatments in the Colo205 model was determined.

PMID- 22469242
TI  - 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography, computed tomography,
      and magnetic resonance imaging for the detection of experimental colorectal liver
      metastases.
AB  - During the treatment of colorectal liver metastases, evaluation of treatment
      efficacy is of the utmost importance for decision making. The aim of the present
      study was to explore the ability of preclinical imaging modalities to detect
      experimental liver metastases. Nine male Wag/Rij rats underwent a laparotomy with
      intraportal injection of CC531 tumor cells. On days 7, 10, and 14 after tumor
      induction, sequential positron emission tomography (PET), computed tomography
      (CT), and magnetic resonance imaging (MRI) scans were acquired of each rat. At
      each time point, three rats were euthanized and the metastases in the liver were
      documented histologically. Topographically, the liver was divided into eight
      segments and the image findings were compared on a segment-by-segment basis with
      the histopathologic findings. Sixty-four liver segments were analyzed, 20 of
      which contained tumor deposits. The overall sensitivity of PET, CT, and MRI was
      30%, 25%, and 20%, respectively. For the detection of tumors with a histologic
      diameter exceeding 1 mm (n  =  8), the sensitivity of PET, CT, and MRI was 63%,
      38%, and 38%, respectively. The overall specificity of PET, CT, and MRI was 98%,
      100%, and 93%, respectively. This study showed encouraging detectability and
      sensitivity for preclinical imaging of small liver tumors and provides valuable
      information on the imaging techniques for designing future protocols.

PMID- 22469243
TI  - Magnetic resonace-based attenuation correction for micro-single-photon emission
      computed tomography.
AB  - Attenuation correction is necessary for quantification in micro-single-photon
      emission computed tomography (micro-SPECT). In general, this is done based on
      micro-computed tomographic (micro-CT) images. Derivation of the attenuation map
      from magnetic resonance (MR) images is difficult because bone and lung are
      invisible in conventional MR images and hence indistinguishable from air. An
      ultrashort echo time (UTE) sequence yields signal in bone and lungs. Micro-SPECT,
      micro-CT, and MR images of 18 rats were acquired. Different tracers were used:
      hexamethylpropyleneamine oxime (brain), dimercaptosuccinic acid (kidney),
      colloids (liver and spleen), and macroaggregated albumin (lung). The micro-SPECT
      images were reconstructed without attenuation correction, with micro-CT-based
      attenuation maps, and with three MR-based attenuation maps: uniform, non-UTE-MR
      based (air, soft tissue), and UTE-MR based (air, lung, soft tissue, bone). The
      average difference with the micro-CT-based reconstruction was calculated. The UTE
      MR-based attenuation correction performed best, with average errors <= 8% in the
      brain scans and <= 3% in the body scans. It yields nonsignificant differences for
      the body scans. The uniform map yields errors of <= 6% in the body scans. No
      attenuation correction yields errors >= 15% in the brain scans and >= 25% in the
      body scans. Attenuation correction should always be performed for quantification.
      The feasibility of MR-based attenuation correction was shown. When accurate
      quantification is necessary, a UTE-MR-based attenuation correction should be
      used.

PMID- 22469244
TI  - Human aortic endothelial cell labeling with positive contrast gadolinium oxide
      nanoparticles for cellular magnetic resonance imaging at 7 Tesla.
AB  - Positive T1 contrast using gadolinium (Gd) contrast agents can potentially
      improve detection of labeled cells on magnetic resonance imaging (MRI). Recently,
      gadolinium oxide (Gd2O3) nanoparticles have shown promise as a sensitive T1 agent
      for cell labeling at clinical field strengths compared to conventional Gd
      chelates. The objective of this study was to investigate Gado CELLTrack, a
      commercially available Gd2O3 nanoparticle, for cell labeling and MRI at 7 T.
      Relaxivity measurements yielded r1  =  4.7 s-1 mM-1 and r2/r1  =  6.2. Human
      aortic endothelial cells were labeled with Gd2O3 at various concentrations and
      underwent MRI from 1 to 7 days postlabeling. The magnetic resonance relaxation
      times T1 and T2 of labeled cell pellets were measured. Cellular contrast agent
      uptake was quantified by inductively coupled plasma-atomic emission spectroscopy,
      which showed very high uptake compared to conventional Gd compounds. MRI
      demonstrated significant positive T1 contrast and stable labeling on cells.
      Enhancement was optimal at low Gd concentrations, attained in the 0.02 to 0.1 mM
      incubation concentration range (corresponding cell uptake was 7.26 to 34.1 pg
      Gd/cell). Cell viability and proliferation were unaffected at the concentrations
      tested and up to at least 3 days postlabeling. Gd2O3 is a promising sensitive and
      stable positive contrast agent for cellular MRI at 7 T.

PMID- 22469245
TI  - Blocked atrial bigeminy presenting with bradycardia.
AB  - Blocked premature atrial contractions can cause bradycardia by resetting
      sinoatrial node and prolonging the RR intervals. Herein, we report the management
      of a patient with frequent premature atrial contractions in bigeminal pattern.
      The patient presented with symptomatic bradycardia and was successfully treated
      with propafenone.

PMID- 22469246
TI  - Hyponatraemia: an overview of frequency, clinical presentation and complications.
AB  - Hyponatraemia (defined as a serum sodium concentration <136 mmol/L) is the most
      frequently encountered electrolyte disturbance in clinical practice. It is
      classified according to volume status (hypovolaemia, hypervolaemia or
      euvolaemia), reflecting the relative proportions of water and sodium within the
      body. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is
      the most common cause of euvolaemic hyponatraemia. Although hyponatraemia is
      associated with poor prognosis and increased length of hospital stay, it is often
      poorly managed and sometimes underdiagnosed and undertreated. This article
      provides an overview of the frequency, pathophysiology and complications
      associated with this common clinical condition.

PMID- 22469247
TI  - Considerations regarding the management of hyponatraemia secondary to SIADH.
AB  - Treatment of hyponatraemia secondary to the syndrome of inappropriate secretion
      of antidiuretic hormone (SIADH) should be guided by the symptomatology of the
      patient, which can be used as a surrogate for the duration of the hyponatraemia.
      However, in patients with acute symptomatic hyponatraemia (developing in <48
      hours), the need to actively treat hyponatraemia is more imperative due to the
      potential risks associated with leaving hyponatraemia untreated (including the
      potential for development of serious neurological manifestations, such as
      seizures and brain stem herniation). In patients with hyponatraemia care needs to
      be taken not to exceed the recommended rates of correction, as this increases the
      risk of osmotic demyelination syndrome. This article will discuss the potential
      impact of prompt intervention in the treatment of hyponatraemia, particularly
      secondary to SIADH, and the need to weigh the benefits of treatment against the
      potential risks associated with overly rapid correction.

PMID- 22469248
TI  - Perspectives on the management of hyponatraemia secondary to SIADH across Europe.
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is the
      most common cause of euvolaemic hyponatraemia. However, although first described
      over 50 years ago, the management of hyponatraemia secondary to SIADH is not
      always straightforward. Some of the issues surrounding the management of
      hyponatraemia secondary to SIADH were explored in the European Hyponatraemia
      Survey completed by attendees of the European Hyponatraemia Network Academy
      Meeting 2011. This article describes the findings of this survey and the specific
      issues raised regarding the management of hyponatraemia secondary to SIADH in
      Europe. Some of these issues - including awareness, education, diagnosis,
      management and cost considerations of the condition - were common to countries
      across Europe.

PMID- 22469249
TI  - Differential diagnosis of hyponatraemia.
AB  - The appropriate management of hyponatraemia is reliant on the accurate
      identification of the underlying cause of the hyponatraemia. In the light of
      evidence which has shown that the use of a clinical algorithm appears to improve
      accuracy in the differential diagnosis of hyponatraemia, the European
      Hyponatraemia Network considered the use of two algorithms. One was developed
      from a nephrologist's view of hyponatraemia, while the other reflected the
      approach of an endocrinologist. Both of these algorithms concurred on the
      importance of assessing effective blood volume status and the measurement of
      urine sodium concentration in the diagnostic process. To demonstrate the
      importance of accurate diagnosis to the correct treatment of hyponatraemia,
      special consideration was given to hyponatraemia in neurosurgical patients. The
      differentiation between the syndrome of inappropriate antidiuretic hormone
      secretion (SIADH), acute adrenocorticotropic hormone (ACTH) deficiency, fluid
      overload and cerebral salt-wasting syndrome was discussed. In patients with
      SIADH, fluid restriction has been the mainstay of treatment despite the absence
      of an evidence base for its use. An approach to using fluid restriction to raise
      serum tonicity in patients with SIADH and to identify patients who are likely to
      be recalcitrant to fluid restriction was also suggested.

PMID- 22469250
TI  - Methicillin-susceptible Staphylococcus aureus ST398, New York and New Jersey,
      USA.

PMID- 22469251
TI  - Evaluation of bactericidal effects of low-temperature nitrogen gas plasma towards
      application to short-time sterilization.
AB  - To develop a novel low-temperature plasma sterilizer using pure N(2)  gas as a
      plasma source, we evaluated bactericidal ability of a prototype apparatus
      provided by NGK Insulators. After determination of the sterilizing conditions
      without the cold spots, the D value of the BI of Geobacillus stearothermophilus
      endospores on the filter paper was determined as 1.9 min. However, the
      inactivation efficiency of BI carrying the same endospores on SUS varied to some
      extent, suggesting that the bactericidal effect might vary by materials of
      sterilized instruments. Staphylococcus aureus and Escherichia coli were also
      exposed to the N(2)  gas plasma and confirmed to be inactivated within 30 min.
      Through the evaluation of bactericidal efficiency in a sterilization bag, we
      concluded that the UV photons in the plasma and the high-voltage pulse to
      generate the gas plasma were not concerned with the bactericidal effect of the
      N(2)  gas plasma. Bactericidal effect might be exhibited by activated nitrogen
      atoms or molecular radicals.

PMID- 22469252
TI  - Impact of a new refrigerator on the preservation of hepatic grafts.
AB  - AIM:   Current medical transplantation methods focus on solutions for major
      problems such as the shortage of donors. To overcome these issues, expanding
      organ preservation time has become a major concern. A new refrigerating chamber
      has been recently developed, which can cool the inside of a material to the
      required temperature by frequently sensing the temperature of both inside and
      surface of the materials. The purpose of this study is to evaluate the usefulness
      of a new refrigerating system in hepatic preservation. METHODS:   The liver
      grafts were harvested from rats and divided into two groups. Group A consisted of
      grafts preserved in chilled University of Wisconsin solution (UW) solution (on
      ice) for 24, 72 and 168 h. Group B consisted of grafts preserved in the UW
      solution in a new refrigerator at 4 degrees C. RESULTS:   In group B, aspartate
      aminotransferase released into effluent after cold storage for 72 h showed a
      marked decrease compared to group A (P < 0.05). The levels of ammonia and lactate
      decreased significantly in group B (P < 0.05). In group B, the levels of
      adenosine triphosphate were significantly preserved after cold storage for 24 h
      and 72 h compared to group A (P < 0.05). Immunohistochemistry showed positive
      cells for heme oxygenase-1 were significantly increased in group B after cold
      storage. CONCLUSION:   This new refrigerator can improve preservation injury of
      hepatic grafts and may provide an innovative technique for liver transplantation.

PMID- 22469253
TI  - Degenerating regenerating torsades de pointes.
AB  - Ventricular fibrillation (VF) commonly ends in death. Isolated case reports
      describe the uncommon occurrence of spontaneous termination of VF. Torsades de
      pointes (TdP), a peculiar form of polymorphic ventricular tachycardia associated
      with a prolonged QT interval on the surface electrocardiogram, most often
      spontaneously terminates and then returns to the underlying rhythm. Here, we
      present an unusual case of TdP degenerating into VF, reorganizing into TdP, and
      then spontaneously terminating. Our case suggests that the mechanisms underlying
      the maintenance of TdP and VF are not dissimilar. The precipitants to this event
      and the likely mechanisms operative are discussed.

PMID- 22469255
TI  - Detection of a new HLA-B*15 allele, HLA-B*15:238, in a voluntary stem cell donor.
AB  - The newly detected HLA-B*15:238 is distinguished from HLA-B*15:52 by a single
      nucleotide exchange at position 527 where T is replaced by A.

PMID- 22469256
TI  - Direct infusion of fenoldopam into the renal arteries to protect against contrast
      induced nephropathy in patients at increased risk.
AB  - 1. Fenoldopam is a dopamine-like receptor agonist that selectively increases
      renal medullary blood flow. Despite promising pathophysiology, randomized
      controlled trials have failed to show a benefit with intravenous infusion of
      fenoldopam in preventing contrast-induced nephropathy (CIN). 2. The aims of the
      present study were to examine the efficacy of intrarenal (i.r.) fenoldopam in
      preventing CIN in high-risk patients undergoing coronary angiograms and
      percutaneous revascularization. 3. The present study was a single centre,
      retrospective observational matched cohort study that included 52 patients at
      risk of developing CIN to whom i.r. fenoldopam was given during catheter-based
      coronary procedures. For each patient treated, a control patient was identified
      on basis of an identical Mehran score. Observed rates of CIN and in-hospital
      dialysis were compared between the i.r. fenoldopam and control groups. 4. Direct
      comparison of the 52 patients treated with i.r. fenoldopam and the 52 matched
      controls revealed that the two groups had similar baseline clinical
      characteristics and creatinine levels (2.4 +/- 0.7 vs. 2.2 +/- 0.6 mg/dL; P =
      0.12). In the i.r. fenoldopam group, six patients (11.5%) developed CIN, compared
      with 16 patients in the control group (30.8%; risk ratio 0.38; 95% confidence
      interval 0.16-0.88; P = 0.012). 5. None of the patients in the fenoldopam group
      needed in-hospital dialysis, compared with three patients in the control group.
      6. A larger prospective randomized study is needed to prove the effectiveness of
      this protective approach.

PMID- 22469257
TI  - Neurobehcet disease: clinical and demographic characteristics.
AB  - BACKGROUND: Neurobehcet disease (NBD) is a rare complication of Behcet disease
      (BD) but with important burdens of morbidity and mortality. Little is known about
      this complication because there are no validated diagnostic criteria, and all the
      studies have small number of patients. The prevalence reported normally ranges
      between 5% and 15% and it is more frequent amongst men between 20 and 40 years
      old. The typical presentations include focal parenchymal lesions, vascular
      thrombosis, arterial vasculitis, and aseptic meningo-encephalitis. METHODS: We
      retrospectively studied medical histories of all patients admitted to the
      hospital and discharged from it with diagnosis of BD from January 1996 to
      September 2009. NBD was defined as having neurological and/or psychiatric
      symptoms with compatible abnormalities in MRI and/or cerebrospinal fluid and
      without another possible explanation for their symptoms. RESULTS: Behcet disease
      was diagnosed in 25 patients and seven from these patients fulfilled our criteria
      of Neurobehcet disease (28%). Patients with NBD were significantly younger at the
      onset of their symptoms and had a significantly longer evolution until diagnosis
      and treatment compared to patients with non-Neuobehcet disease. Six presented a
      relapsing-remitting pattern, with a good outcome with corticosteroids.
      CONCLUSIONS: As reported in previous studies, progressive course was less
      frequent, with only one case, and had a more aggressive disease. Brainstem
      involvement bears a poorer prognosis because it is linked with a progressive
      evolution. In our series, NBD complication was not that infrequent. It is very
      important to be highly suspicious of this possibility to start early a correct
      treatment.

PMID- 22469258
TI  - Buclizine.
AB  - A comprehensive profile on buclizine hydrochloride, the piperazine derivative
      which is a sedating antihistamine with antimuscarinic and moderate sedative
      action and used mainly for its antiemetic effect in the prevention of motion
      sickness and migraine, is prepared. This profile contains the following sections:
      description, uses and applications, methods of preparation, physical
      characteristics, methods of analysis and stability. The physical characteristics
      section includes solubility, melting range, X-ray powder diffraction pattern,
      ultraviolet/visible spectroscopy, infrared spectroscopy, proton and carbon-13
      nuclear magnetic resonance spectrometry, and mass spectrometry. Methods of
      analysis section includes compendial BP methods, spectrophotometry,
      potentiometry, and chromatography (TLC, GC, HPLC).

PMID- 22469254
TI  - Child development and molecular genetics: 14 years later.
AB  - Fourteen years ago, the first article on molecular genetics was published in this
      journal: Child Development, Molecular Genetics, and What to Do With Genes Once
      They Are Found (R. Plomin & M. Rutter, 1998). The goal of the article was to
      outline what developmentalists can do with genes once they are found. These new
      directions for developmental research are still relevant today. The problem lies
      with the phrase "once they are found": It has been much more difficult than
      expected to identify genes responsible for the heritability of complex traits and
      common disorders, the so-called missing heritability problem. The present article
      considers reasons for the missing heritability problem and possible solutions.

PMID- 22469259
TI  - Chitin.
AB  - A comprehensive profile of chitin with 61 references is reported. A full
      description including nomenclature, formulae, elemental analysis, and appearance
      is included. Methods of preparation for chitin and its derivative, such as
      chitosan, are discussed. Physical properties, analytical methods, uses and
      applications, stability, biodegradability, and toxicity of chitin are also
      reviewed.

PMID- 22469260
TI  - Ezetimibe.
AB  - Ezetimibe is a drug substance which can be used for lowering low-density
      lipoprotein cholesterol. Its crystal form and polymorphism have been determined
      using X-ray diffraction and thermal methods. Quantitative and qualitative
      analysis of Ezetimibe as well as study of its impurities and degradations were
      summarized in this chapter.

PMID- 22469261
TI  - Gemifloxacin.
AB  - A comprehensive profile on Gemifloxacin, a novel fluoroquinolone synthetic broad
      spectrum antibacterial agent for oral administration, particularly indicated for
      treatment of community-acquired respiratory tract infections, such as pneumonia
      and acute bacterial exacerbations of chronic bronchitis, is prepared. This
      profile contains the following sections: introduction, general physicochemical
      informations, X-ray powder diffraction patterns, methods of preparations, methods
      of analysis and stability, spectroscopic methods of investigations, and
      identifications including ultraviolet/visible spectroscopy, infrared
      (vibrational) spectroscopy, proton and carbon-13 nuclear magnetic resonance
      spectrometry, and mass spectrometry. Section 7 includes compendial BP
      identification methods, thin-layer chromatography, gas chromatography, high
      performance liquid chromatography. The pharmacological applications section
      includes uses, mode of action, pharmacokinetics, and toxicity investigations.

PMID- 22469262
TI  - Glimepiride.
AB  - Glimepiride, which belongs to the sulfonylurea group, has been widely analyzed
      for its physical chemical properties including its crystallinity. Moreover,
      methods to quantify glimepiride and its impurities, either in pharmaceutical
      dosage form or in biological sample, have also been extensively developed and
      reported. This chapter extracts all information needed to give more perspective
      regarding to this substance.

PMID- 22469263
TI  - Lornoxicam.
AB  - A comprehensive profile on lornoxicam, the oxicam nonsteroidal anti-inflammatory
      agent which is used in the muscular skeletal and joint disorders such as
      osteoarthritis and rheumatoid arthritis, is prepared. This profile contains the
      following sections: description, uses and applications, methods of preparation,
      physical characteristics, methods of analysis, mechanism of action,
      pharmacokinetics, reviews, and stability. The physical characteristics section
      includes ionization constant, solubility, partition coefficient, thermal methods
      of analysis. X-ray powder diffraction pattern, crystal structure, ultraviolet
      spectroscopy, vibrational spectroscopy, proton and carbon-13 nuclear magnetic
      resonance spectrometry, and mass spectrometry. Methods of analysis section
      includes spectrophotometry, polarography, and chromatography (TLC, HPLC, HPLC
      MS).

PMID- 22469264
TI  - Magnesium silicate.
AB  - A comprehensive profile of magnesium silicate with 80 references is reported. A
      full description including nomenclature, formulae, and appearance is included.
      Methods for magnesium silicate preparation including precipitation, hydrothermal
      precipitation, and mechanochemical dehydration are reviewed. Physical
      characteristics, compendia and non-compendia analytical methods, uses, stability
      and incompatibilities, biodegradability, toxicity, and substances related to
      magnesium silicate are also discussed.

PMID- 22469265
TI  - Tadalafil.
AB  - Tadalafil is PDE5 inhibitor that has recently been approved for the treatment of
      ED. The mechanism of action of tadalafil is similar to sildenafil and vardenafil
      through the inhibition of PDE. In both chemical structure and PDE subtype
      selectivity profile, tadalafil differs markedly from sildenafil and vardenafil.
      Compared with sildenafil and vardenafil, tadalafil exhibits a prolonged plasma
      residence and window of therapeutic response. The physical properties,
      spectroscopic data and chromatographic methods of determination of tadalafil are
      documented.

PMID- 22469266
TI  - Direct crystallization of enantiomers and dissociable diastereomers.
AB  - Molecules whose mirror images cannot be superimposed on each other are identified
      as being chiral, and a very important branch of separation science has developed
      around the resolution of compounds having pharmaceutical interest. At one time,
      scientists associated the phenomenon of optical rotation with the presence of
      carbon atoms bound to four different molecular fragments, and these
      asymmetrically substituted carbon atoms became known as "asymmetric carbons."
      Continued work showed that compounds incapable of rotating the plane of polarized
      light, but which were known to contain at least one asymmetric carbon atom, could
      be separated into chemically identical "optical isomers" that now exhibited the
      phenomenon of optical rotation. Over time, it became clear that optical activity
      could exist in compounds having no asymmetric atoms, and that other compounds
      existed that contained two or more asymmetric carbons, but still could not be
      rendered optically active. These findings necessitated a return to the proposal
      of Pasteur, who held that optical activity is a consequence of molecular
      dissymmetry. In other words, a molecule superimposable with its mirror image
      cannot be optically active, and any molecule not superimposable with its mirror
      image will exhibit optical activity.

PMID- 22469267
TI  - Cocrystal systems of pharmaceutical interest: 2009.
AB  - As scientists become more aware of a substantial expansion in the scope of solid
      state structural variations that can be obtained through the cocrystallization of
      several molecules in a single lattice structure, studies of the mixed molecular
      crystal systems known as cocrystals have mushroomed. Along these lines, workers
      have researched the assembly of supramolecular synthons and crystal engineering
      in ever-increasing efforts to produce materials having new and useful properties.
      For the purposes of this review, cocrystal systems will be regarded as those
      mixed crystal systems where the individual components exist as solids under
      ambient conditions. Particularly useful guidance has been provided by Aakeroy,
      where cocrystal formation from supramolecular synthons is to be considered as
      forming from discrete neutral molecular species that are solids at ambient
      temperatures, and where the cocrystal is a structurally homogeneous crystalline
      material that contains the building blocks in definite stoichiometric amounts.

PMID- 22469268
TI  - Series editors.

PMID- 22469269
TI  - Preface to volume 36.

PMID- 22469271
TI  - Retention of CAD/CAM all-ceramic crowns on prefabricated implant abutments: an in
      vitro comparative study of luting agents and abutment surface area.
AB  - PURPOSE: Previous studies considering retention of cast metal restorations to
      implant abutments incorporated some degree of frictional fit due to internal
      surface nodules and roughness of the restoration. In comparison, CAD/CAM
      restorations have minimal surface irregularities, possibly impacting retention.
      There is insufficient knowledge of retentive force of CAD/CAM restorations to
      titanium abutments, and therefore the topic warrants further investigation. This
      in vitro study investigated the retention of all-ceramic CAD/CAM restorations to
      three different prefabricated implant abutments using five different cements.
      MATERIALS AND METHODS: A total of 150 Astra Tech dental implant abutments were
      used, with each group of 50 being subdivided into five groups of 10. An optical
      impression of each size of abutment was made with the CEREC 3D intraoral camera.
      A full-coverage restoration was designed and milled with an enlarged, conical
      shaped occlusal surface, which served to secure the restoration into a brass jig
      used with a universal testing machine. Five different cements were used with
      three different-sized abutments. Following cementation, the
      implant/abutment/restoration assemblies were stored for 24 hours at 37 degrees C
      in 100% humidity. A pull-out test using a universal testing machine, set at a 0.5
      mm/min crosshead speed, was used to evaluate retention of the individual
      restorations. The load required to remove each all-ceramic restoration was
      recorded. Retention values were analyzed using ANOVA and Fisher's PLSD multiple
      comparisons test at the 0.05 level of significance. RESULTS: Peak loads for two
      provisional cements and a resin-modified glass ionomer cement ranged from 56 N to
      127 N. Peak loads for two resin cements ranged from 184 N to 318 N. Two-way ANOVA
      showed significant effects upon retentive forces for both the cement and abutment
      design. Post hoc Fisher's PLSD multiple comparisons test found significant
      differences in retention for 7 of the 10 pairings of cements at a 0.05 level of
      significance. In addition, Fisher's PLSD multiple comparisons test found
      significant differences between Astra Tech Direct Abutments 4 and Astra Tech
      Direct Abutments 5 as well as Astra Tech Direct Abutments 4 and Astra Tech Direct
      Abutments 6 at a 0.05 level of significance. No significant difference was found
      between Astra Tech Direct Abutments 5 and Astra Tech Direct Abutments 6.
      CONCLUSIONS: Of the five cements tested, the most retrievable CAD/CAM
      restorations were luted with Temp Bond NE and Improv Temporary Cement. Resin
      modified glass ionomer retentive forces were closer to those of the "temporary
      cements" than those of the permanent adhesive-resin cements. The abutment surface
      area became less important when using adhesive-resin cements. Retention of
      CAD/CAM all-ceramic restorations to prefabricated abutments has not been reported
      in the literature. This in vitro study demonstrated clinically significant
      variation among the selected cements used to retain all-ceramic CAD/CAM
      restorations to implant abutments. In addition, abutment size influenced the
      retention of all-ceramic CAD/CAM restorations.

PMID- 22469272
TI  - Suppression of astrocyte lineage in adult hippocampal progenitor cells expressing
      hippocampal cholinergic neurostimulating Peptide precursor in an in vivo ischemic
      model.
AB  - Hippocampal cholinergic neurostimulating peptide (HCNP) is known to promote
      differentiation of septohippocampal cholinergic neurons. The HCNP precursor
      protein (HCNP-pp) may play several roles, for example, as an ATP-binding protein,
      a Raf kinase inhibitor protein, and a phosphatidylethanolamine-binding  protein,
      as well as a precursor for HCNP. This study therefore aimed to elucidate the
      involvement of HCNP-pp in specific neural lineages after stroke using a hypoxic
      ischemic (HI) rat model of brain ischemia. The specific neural lineages in the
      hippocampus were investigated 14 days after ischemia.  Some bromodeoxyuridine
      (BrdU)(+) neural progenitor cells in the hippocampus of hypoxic, HI, or sham
      operated rats expressed HCNP-pp. Almost half of the BrdU(+)/HCNP-pp(+) cells also
      expressed the oligodendrocyte lineage marker 2',3'-cyclic nucleotide  3'
      phosphodiesterase, whereas only a few BrdU(+)/HCNP-pp(+) cells in the hippocampus
      in HI brains expressed the neuronal lineage marker, doublecortin (DCX).
      Interestingly, no BrdU(+)/HCNP-pp(+) progenitor cells in hypoxic, HI, or sham
      operated brains  expressed the astrocyte lineage marker, glial fibrillary acidic
      protein. Together with previous in vitro data, the results of this study suggest
      that the expression level of HCNP-pp regulates the differentiation of neural
      progenitor cells into specific neural lineages in the HI hippocampus,  indicating
      that neural stem cell fate can be controlled via the HCNP-pp mediating pathway.

PMID- 22469273
TI  - Seasonal reduction in vitamin D level persists into spring in NSW Australia:
      implications for monitoring and replacement therapy.
AB  - CONTEXT: Seasonal variation in 25-hydroxyvitamin D [25OHD] status and its
      relationship to gender, age, socioeconomic and geographic determinants in
      Australians has not been described in large biomedical sampling cohorts.
      OBJECTIVES: To analyse 25OHD levels in all primary tests undertaken consecutively
      in a 2-year period to determine the prevalence of 25OHD deficiency and its
      relation to patient setting, gender, age, season, urban or rural residency,
      socioeconomic status, latitude and longitude. DESIGN: We assessed 24 819
      ambulatory and inpatient samples taken from the largest reference laboratory in
      NSW, Australia between 01 July 2008 and 30 July 2010. MAIN OUTCOME MEASURES:
      Serum 25OHD was measured using chemiluminescent immunoassay. Vitamin D deficiency
      was defined as 25OHD <50 nm. RESULTS: Median 25OHD was 54 nm ranging from 63 nm
      in summer to 44 nm in spring and was lowest in inpatient women (49 nm) and
      highest in ambulatory men (64 nm). Mean 25OHD peaked in January (67 nm) and
      reached a nadir in August/September (39 nm). During summer, 36% subjects overall
      had a level below 50 nm, increasing to 58% in spring. The highest prevalence of
      deficiency occurred in female inpatients (42% in summer and 62% in spring).
      Factors associated with lower 25OHD included being tested in spring, an
      inpatient, female, aged 20-39 or >79 years, socioeconomically disadvantaged and
      from a major city. CONCLUSION: This cross-sectional study demonstrates the extent
      and duration of 25OHD deficiency is greater than expected, and particular
      individuals are at higher risk. Our findings imply that supplementation
      guidelines need to be modified and strengthened.

PMID- 22469274
TI  - When prevention is a bad idea: problems with the DECARD trial and the premise
      behind it.

PMID- 22469275
TI  - Associations between dimensional personality measures and preclinical
      atherosclerosis: the cardiovascular risk in Young Finns study.
AB  - OBJECTIVE: To assess how multidimensional personality-trait theories, such as the
      Psychobiological Model of Temperament and Character, and the Five-factor Model of
      Personality, are associated with subclinical atherosclerosis as indicated by
      carotid intima-media thickness (IMT). The analysis was designed to tolerate non
      linear development in which the same personality profiles can have multiple final
      outcomes and different antecedent profiles can have the same final outcome.
      METHODS: 605 men and 844 women (average age 31.6year, s.d.=5.0, range=24-39)
      provided data on IMT and traits of the psychobiological model, 725 men and 1011
      women were assessed for IMT and the five-factor model (age 37.7year, s.d.=5.0,
      range=30-45). Robust multidimensional Hotelling's T(2) statistic was used to
      detect personality differences between participants with high IMT and others.
      Model-based clustering method further explored the effect. RESULTS: Those with a
      high level of subclinical atherosclerosis within the sample (highest IMT-decile)
      had a combined higher persistence (i.e., were perseverative or perfectionistic),
      more disorganized (schizotypal) character, and more antisocial temperamental
      configuration than others (P=0.019). No effect was found for the five-factor
      model (P=0.978). Traditional methods that did not account for multidimensionality
      and nonlinearity did not detect an association. CONCLUSION: Psychological well
      being may have positive effects on health that reduce atherosclerosis in the
      population as a whole. Increased subclinical atherosclerosis was associated with
      a profile that combines known risk factors, such as cynical distrust and hostile
      tendencies. More frequent use of statistical procedures that can cope with non
      linear interactions in complex psychobiological systems may facilitate scientific
      advances in health promotion.

PMID- 22469276
TI  - Parental cancer: factors associated with children's psychosocial adjustment--a
      systematic review.
AB  - OBJECTIVE: Children of cancer patients have an increased risk of developing
      psychosocial problems. But not all children are alike vulnerable to this
      stressful event. Thus, knowledge of risk and protective factors is required to
      design specific diagnostic tools and interventions for this vulnerable
      population. This study aims to provide a review and methodological evaluation of
      current studies examining factors associated with children's psychosocial
      adjustment when a parent has cancer. METHODS: Four databases were systematically
      searched for quantitative research articles examining associative factors of
      children's adjustment. Study characteristics were analyzed and methodological
      quality was assessed by two independent reviewers. RESULTS: 28 studies examining
      associative factors in 2896 families were identified. The included studies used a
      broad range of instruments assessing children's adjustment. Most patients were
      female breast cancer patients with middle to high socio-economic status. The
      majority of included studies used correlational approaches and cross-sectional
      designs. None of the studies examined toddlers or assessed children's quality of
      life. Across studies with low to high quality, we found no evidence of illness
      related factors, except worse disease status that was related to lower
      adjustment. Evidence from moderate to high quality studies suggest that better
      family functioning indicates better adjustment, whereas parent's depressive mood
      indicates worse adjustment of the children. Child-related factors were
      inconsistent. CONCLUSION: Health professionals should pay attention to cancer
      patients' dependent children. In order to identify this at-risk population,
      parent's depressive mood and poor family functioning should be considered. Future
      studies should also assess children's quality of life and child-related factors.

PMID- 22469277
TI  - Role of older adult's illness schemata in coping with mild cognitive impairment.
AB  - OBJECTIVE: 1) To describe the illness representations of older persons with Mild
      Cognitive Impairment (MCI); 2) to describe how older adults cope with MCI; 3) to
      examine the relationships between illness representations and coping. METHODS:
      Sixty-three older adults with MCI completed questionnaires on demographic and
      health information, beliefs about MCI (Illness Perception Questionnaire-MCI), and
      coping with MCI (brief COPE and Self-care Behaviors Checklist). RESULTS:
      Participants endorsed an average of 7 symptoms that they experienced and believed
      were related to MCI and an average of 7 potential causes of MCI. Participants
      tended to believe MCI was chronic, not cyclic, and controllable, but they
      differed in their beliefs about the consequences, understandability and emotional
      impact of MCI. Participants used many dementia prevention behaviors and memory
      aids, some problem-focused and emotion-focused coping strategies, and few
      dysfunctional coping strategies. Cluster analysis identified three clusters of
      beliefs about MCI: "few symptoms and positive beliefs," "moderate symptoms and
      positive beliefs," and "many symptoms and negative beliefs." Those in the "many
      symptoms and negative beliefs" cluster had significantly more negative beliefs
      about the consequences, unpredictability (cyclic timeline), and emotional impact
      of MCI than those in the other clusters. Participants in the "few symptoms and
      positive beliefs" cluster used significantly fewer memory aids, problem-focused
      coping strategies, emotion-focused coping strategies, and dysfunctional coping
      than those in the other two clusters. CONCLUSION: As suggested by the Common
      Sense Model, older adults with MCI have beliefs about their MCI and these beliefs
      are associated with how older adults cope with MCI.

PMID- 22469278
TI  - Associations between adult attachment style and health risk behaviors in an adult
      female primary care population.
AB  - OBJECTIVE: To examine the relationship between adult attachment style and health
      risk behaviors among adult women in a primary care setting. METHODS: In this
      analysis of a population of women enrolled in a large health maintenance
      organization (N=701), we examined the relationship between anxious and avoidant
      dimensions of adult attachment style and a variety of sexual, substance-related,
      and other health risk behaviors. After conducting descriptive statistics of the
      entire population, we determined the relationships between the two attachment
      dimensions and health behaviors using multiple regression analyses in which we
      controlled for demographic and socioeconomic factors. RESULTS: After adjustment
      for covariates, the anxious dimension of attachment style was significantly
      associated with increased odds of self-report of having sex without knowing a
      partner's history, having multiple (>=2) male partners in the past year, and
      history of having a sexually transmitted infection (ORs [95% CIs]=1.11 [1.03,
      1.20], 1.23 [1.04, 1.45]; and 1.17 [1.05, 1.30], respectively). The avoidant
      attachment dimension was associated with increased odds of being a smoker and not
      reporting regular seatbelt use (ORs [95% CIs]=1.15 [1.01, 1.30] and 1.16 [1.01,
      1.33], respectively). CONCLUSIONS: Both anxious and avoidant dimensions of
      attachment were associated with health risk behaviors in this study. This
      framework may be a useful tool to allow primary care clinicians to guide
      screening and intervention efforts.

PMID- 22469279
TI  - Depressive symptoms and unprotected sex in St. Petersburg, Russia.
AB  - OBJECTIVE: Growing evidence indicates that emotional distress such as depression
      may have the potential to increase the risk for HIV and other sexually
      transmitted infections (STIs). This study investigated the association between
      depressive symptoms and unprotected sex among STI clinic patients in Russia.
      METHODS: We used pre-intervention data collected between 2009 and 2010 among 307
      participants who were enrolled in a randomized intervention trial conducted in an
      STI clinic in St. Petersburg, Russia. The 10-item Center for Epidemiological
      Studies Depression Scale was used to identify depressive symptoms and two
      indicators were used to measure unprotected sex. Logistic regression models were
      applied for the analysis and controlled for the following potential confounders:
      demographic characteristics, being a commercial sex worker, history of drug
      injection and alcohol misuse. RESULTS: Of the participants, 20.2% were classified
      as having depressive symptoms. About 59.6% of the participants did not use a
      condom during the last sexual intercourse and 24.4% never used condoms in the
      past 3months. Depressive symptoms were significantly associated with both
      indicators of unprotected sex in two different models: odds ratio (OR)=2.36, 95%
      confidence interval (CI), 1.24-4.48 for unprotected sex in the last sexual
      intercourse; and OR=2.71, 95% CI, 1.43-5.11 for unprotected sex in the past
      3months. CONCLUSION: Depressive symptoms were common and were strongly associated
      with unprotected sex among study participants in St. Petersburg, Russia. Efforts
      to promote condom use should address lack of condom use due to depressive
      symptoms.

PMID- 22469281
TI  - Biogenetic temperament and character in insomnia and depression.
AB  - OBJECTIVE: We compared the biogenetic temperaments and characters of primary
      insomnia patients, major depressive disorder (MDD) patients with insomnia, MDD
      patients without insomnia, and normal controls. METHODS: A total of 417
      participants were recruited from a community and a psychiatric clinic in South
      Korea. Subjects were divided into 4 groups based on the Structured Clinical
      Interview for DSM-IV axis I disorder (SCID-IV) and sleep questionnaire: 1) normal
      controls (n=314), 2) primary insomnia (n=33), 3) MDD without insomnia (n=30), and
      4) MDD with insomnia (n=40). All participants were requested to complete the
      Temperament and Character Inventory. RESULTS: There were significant between
      group differences in harm avoidance (HA)(F=32.96, p<0.001), reward dependence
      (RD)(F=5.21, p<0.01), self-directedness (SD)(F=24.72, p<0.001) and
      cooperativeness (CO)(F=15.75, p<0.001), after controlling for age and gender.
      Subjects with primary insomnia showed higher HA and lower SD than normal control,
      but lower HA and higher SD than MDD patients with insomnia. CO was lower in MDD
      patients, but not in subjects with primary insomnia. Lower RD was found only in
      MDD patients with insomnia. CONCLUSION: The current study suggests that high HA
      and low SD were related to primary insomnia, although these patterns were more
      prominent in patients with MDD.

PMID- 22469280
TI  - Gender specific temporal and cross-sectional associations between BMI-class and
      symptoms of depression in the elderly.
AB  - OBJECTIVE: The aim of the study was the gender specific analysis of cross
      sectional and longitudinal associations between body mass index class (BMI-class)
      and symptoms of depression in a representative sample of elderly German people.
      METHODS: At the baseline of the ESTHER study (2000-2002), 9953 participants
      completed a comprehensive questionnaire including items regarding weight, height,
      and depression history. After five years, 7808 participants again completed the
      questionnaire and the 15-item geriatric depression scale (GDS-15). BMI was
      classified into five classes: normal weight, 18.5<=BMI<25; overweight,
      25<=BMI<30; obesity class I, 30<=BMI<35; obesity class II, 35<=BMI<40; obesity
      class III, BMI>=40. RESULTS: Logistic regression analysis for the cross-sectional
      data at five-year follow-up, adjusted for age, education, marital status,
      smoking, multimorbidity, physical activity, self-perceived cognitive impairment,
      and use of antidepressants, showed that the odds for depression were
      significantly elevated for women in obesity class II and significantly decreased
      for overweight men. The longitudinal analysis showed a similar pattern: Women in
      obesity classes II and III at baseline had significantly higher odds for being
      depressive five years later than women with normal weight at baseline (class II:
      OR=1.67; 95%CI=[1.06; 2.64]; class III: OR=2.93; 95%CI=[1.37; 6.26]; overweight
      men had lower odds than normal-weight men (OR=0.69; 95%CI=[0.51;0.92]).
      CONCLUSION: The relationship between obesity and symptoms of depression appears
      to be heterogeneous across BMI-classes. Women are more affected than men by
      obesity class II and III; overweight appears to be associated with reduced risk
      of depression in elderly men.

PMID- 22469282
TI  - Catastrophic interpretations and anxiety sensitivity as predictors of panic
      spectrum psychopathology in chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Panic-spectrum psychopathology (denoting panic attacks and panic
      disorder) is highly prevalent in chronic obstructive pulmonary disease (COPD),
      and the cognitive model of panic has been proposed as an explanation of this high
      prevalence. In the current cross-sectional study we investigated factors
      predicting panic-spectrum psychopathology in COPD, and hypothesized that,
      consistent with the cognitive model, both the catastrophic interpretation of
      shortness of breath and elevated anxiety sensitivity would be significant
      predictors when variance shared with confounding variables was controlled.
      METHODS: Sixty-two participants with COPD were interviewed with the Anxiety
      Disorders Interview Schedule for DSM-IV, Panic Disorder section, and completed
      measures of interpretation of breathing difficulty, anxiety sensitivity, anxiety,
      depression, disease-specific quality of life, and stressful life events.
      Objective disease severity was measured using forced expiratory volume in the
      first second. RESULTS: Direct logistic regression was performed, and worse
      depressive symptoms, more catastrophic interpretations of shortness of breath,
      higher anxiety sensitivity, higher magnitude of recent stressful life events, and
      worse disease severity were each found to be significant unique predictors of
      panic-spectrum psychopathology in COPD after shared variance was controlled.
      CONCLUSIONS: The results of the study provide support for the cognitive model of
      panic, and also suggest a diathesis-stress explanation of the development of
      panic-spectrum psychopathology in COPD. The findings have implications for future
      preventative psychological interventions.

PMID- 22469283
TI  - Body mass index and mental health problems in general adults: disparity in gender
      and socioeconomic status.
AB  - OBJECTIVE: This nationwide population-based study aims to evaluate the
      association between Body Mass Index (BMI) and mental health problems, and to
      investigate the effects of gender and socioeconomic status (SES) on this
      association. METHODS: This study was a longitudinal study. 12,862 adults (aged
      18years or older), who responded to the 2001 National Health Interview Survey
      (NHIS) and gave consent to the linking of the survey data to their National
      Health Insurance (NHI) claims records, were included. The 2002-2004 NHI claims
      records of the sample were analyzed. Logistic regression was used to evaluate the
      odds ratios. Those with middle and high income (per capita annual household
      income ?US$9375) in the sample were referred to as the better-offs. RESULTS:
      After adjustment, increased BMI was significantly associated with a higher risk
      of schizophrenia (OR: 1.14, 95% CI: 1.07-1.22) and a lower risk of mood disorder
      (OR: 0.95, 95% CI: 0.91-0.99) in women. In addition, a higher BMI was
      significantly associated with a lower risk of mood disorders (risk reduction: 6%)
      and a lower risk of any major mental health problem (risk reduction: 3%) among
      the better-offs. CONCLUSIONS: In contrast to other (cross-sectional) studies in
      other countries, our longitudinal results suggest that in a general Taiwanese
      population, the association between BMI and mental health may vary by type of
      mental health problems. Gender and SES may have influenced this relationship.
      Further studies are required to elucidate the biological or social factors
      underlying these empirical observations.

PMID- 22469284
TI  - Towards an evidence-based treatment model for cognitive behavioral interventions
      focusing on chronic fatigue syndrome.
AB  - OBJECTIVE: The purpose of the present study was to develop a treatment model for
      cognitive behavioral interventions focusing on chronic fatigue syndrome (CFS)
      based on the model of perpetuating factors introduced by Vercoulen et al.
      [Journal of Psychosomatic Research 1998;45:507-17]. METHODS: For this purpose, we
      reanalyzed the data of a previously conducted randomized controlled trial in
      which a low intensity cognitive behavioral intervention was compared to a waiting
      list control group. Structural equation modeling was used to test a treatment
      model in which changes in focusing on symptoms, perceived problems with activity,
      and sense of control over fatigue were hypothesized to mediate the effect of our
      intervention on fatigue severity and disability. RESULTS: In the final model,
      which had a good fit to the data, the effect of treatment was mediated by a
      decrease in perceived problems with activity and an increase in sense of control
      over fatigue. CONCLUSION: Our findings suggest that cognitive behavioral
      interventions for CFS need to change the illness perception and beliefs of their
      patients in order to be effective.

PMID- 22469285
TI  - Diagnosis and assessment of apathy in Chinese patients with Alzheimer's disease.
AB  - BACKGROUND: Apathy is a major component of the behavioral and psychological
      symptoms of Alzheimer's Disease (AD) and other types of dementia. Most
      researchers have reached a consensus on a new set of diagnostic criteria for
      apathy (DCA) recently. However, no relevant reports on apathy exist for AD
      patients in Asian countries yet. OBJECTIVES: To estimate the prevalence of apathy
      in Chinese AD patients. METHODS: 83 AD patients were recruited for a cross
      sectional observational study. Following the new diagnostic criteria for apathy
      (DCA) and DSM-IV criteria for Major Depressive Disorder (MDD), each patient was
      assessed successively by Mini Mental State Examination (MMSE), the
      Neuropsychiatric Inventory-apathy subscale (NPI-apathy), the Geriatric Depression
      Screening scale (GDS), and the Caregiver Burden Scale (CBS). RESULTS: According
      to the DCA, we found that the frequency of apathy in Chinese AD patients reached
      61.4%. The DCA had very good standard validity and internal consistency. The
      frequency of apathy was not significantly associated with that of depression,
      whereas there was a significant association between apathy and more severe
      cognitive deficits. Caregiver burden was significantly associated with severity
      of apathy. CONCLUSIONS: From the symptoms of a group of Chinese AD patients, we
      summarized a set of effective methods for the diagnosis and assessment of apathy.

PMID- 22469286
TI  - The effect of priming illness memory on pain tolerance: a failed replication.

PMID- 22469287
TI  - Outcomes of autogenic training for patients with chronic subjective dizziness.

PMID- 22469288
TI  - De novo daptomycin-nonsusceptible enterococcal infections.
AB  - Potential emergence of enterococcal daptomycin nonsusceptibility among patients
      with no prior exposure to daptomycin poses clinical and public health challenges.
      We found that development of infections with daptomycin-nonsusceptible
      enterococci in these patients could be associated with sporadic emergence and
      clonal spread.

PMID- 22469289
TI  - The ectomycorrhizal fungus Paxillus involutus converts organic matter in plant
      litter using a trimmed brown-rot mechanism involving Fenton chemistry.
AB  - Soils in boreal forests contain large stocks of carbon. Plants are the main
      source of this carbon through tissue residues and root exudates. A major part of
      the exudates are allocated to symbiotic ectomycorrhizal fungi. In return, the
      plant receives nutrients, in particular nitrogen from the mycorrhizal fungi. To
      capture the nitrogen, the fungi must at least partly disrupt the recalcitrant
      organic matter-protein complexes within which the nitrogen is embedded. This
      disruption process is poorly characterized. We used spectroscopic analyses and
      transcriptome profiling to examine the mechanism by which the ectomycorrhizal
      fungus Paxillus involutus degrades organic matter when acquiring nitrogen from
      plant litter. The fungus partially degraded polysaccharides and modified the
      structure of polyphenols. The observed chemical changes were consistent with a
      hydroxyl radical attack, involving Fenton chemistry similar to that of brown-rot
      fungi. The set of enzymes expressed by Pa. involutus during the degradation of
      the organic matter was similar to the set of enzymes involved in the oxidative
      degradation of wood by brown-rot fungi. However, Pa. involutus lacked transcripts
      encoding extracellular enzymes needed for metabolizing the released carbon. The
      saprotrophic activity has been reduced to a radical-based biodegradation system
      that can efficiently disrupt the organic matter-protein complexes and thereby
      mobilize the entrapped nutrients. We suggest that the released carbon then
      becomes available for further degradation and assimilation by commensal microbes,
      and that these activities have been lost in ectomycorrhizal fungi as an
      adaptation to symbiotic growth on host photosynthate. The interdependence of
      ectomycorrhizal symbionts and saprophytic microbes would provide a key link in
      the turnover of nutrients and carbon in forest ecosystems.

PMID- 22469290
TI  - Dengue and US military operations from the Spanish-American War through today.
AB  - Dengue is a major cause of illness among travelers and a threat to military
      troops operating in areas to which it is endemic. Before and during World War II,
      dengue frequently occurred in US military personnel in Asia and the South
      Pacific. From the 1960s into the 1990s, dengue often occurred in US troops in
      Vietnam, the Philippines, Somalia, and Haiti. We found attack rates as high as
      80% and periods of convalescence up to 3-1/2 weeks beyond the acute illness. The
      increase in dengue throughout the world suggests that it will remain a problem
      for military personnel until an effective vaccine is licensed.

PMID- 22469291
TI  - SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in
      breast cancer patients with distant metastases at initial presentation.
AB  - BACKGROUND: Five percent of all patients with breast cancer have distant
      metastatic disease at initial presentation. Because metastatic breast cancer is
      considered to be an incurable disease, it is generally treated with a palliative
      intent. Recent non-randomized studies have demonstrated that (complete) resection
      of the primary tumor is associated with a significant improvement of the survival
      of patients with primary metastatic breast cancer. However, other studies have
      suggested that the claimed survival benefit by surgery may be caused by selection
      bias. Therefore, a randomized controlled trial will be performed to assess
      whether breast surgery in patients with primary distant metastatic breast cancer
      will improve the prognosis. DESIGN: Randomization will take place after the
      diagnosis of primary distant metastatic breast cancer. Patients will either be
      randomized to up front surgery of the breast tumor followed by systemic therapy
      or to systemic therapy, followed by delayed local treatment of the breast tumor
      if clinically indicated.Patients with primary distant metastatic breast cancer,
      with no prior treatment of the breast cancer, who are 18 years or older and fit
      enough to undergo surgery and systemic therapy are eligible. Important exclusion
      criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of
      this breast tumor before randomization, irresectable T4 tumor and synchronous
      bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life
      and local tumor control are among the secondary endpoints.Based on the results of
      prior research it was calculated that 258 patients are needed in each treatment
      arm, assuming a power of 80%. Total accrual time is expected to take 60 months.
      An interim analysis will be performed to assess any clinically significant safety
      concerns and to determine whether there is evidence that up front surgery is
      clinically or statistically inferior to systemic therapy with respect to the
      primary endpoint. DISCUSSION: The SUBMIT study is a randomized controlled trial
      that will provide evidence on whether or not surgery of the primary tumor in
      breast cancer patients with metastatic disease at initial presentation results in
      an improved survival. TRIAL REGISTRATION: NCT01392586.

PMID- 22469292
TI  - Towards diagnostic guidelines for biofilm-associated infections.
AB  - Biofilms associated with the human body, particularly in typically sterile
      locations, are difficult to diagnose and treat effectively because of their
      recalcitrance to conventional antibiotic therapy and host immune responses. The
      study of biofilms in medicine today requires a translational approach, with
      examination of clinically relevant biofilms in the context of specific anatomic
      sites, host tissues, and diseases, focusing on what can be done to mitigate their
      pathologic consequences. This review, which grew out of a discussion session on
      clinical biofilms at the 5th ASM Biofilm Conference in Cancun, Mexico, is
      designed to give an overview of biofilm-associated infections (BAI) and to
      propose a platform for further discussion that includes clinicians, medical
      microbiologists, and biofilm researchers who are stakeholders in advancing the
      scientific pursuit of better diagnosis and treatment of BAI to mitigate their
      human and healthcare costs. It also highlights the need for better diagnostic
      markers, which exploit the difference between planktonic and biofilm cells.

PMID- 22469293
TI  - Endosomal escape and transfection efficiency of PEGylated cationic liposome-DNA
      complexes prepared with an acid-labile PEG-lipid.
AB  - Cationic liposome-DNA (CL-DNA) complexes are being pursued as nonviral gene
      delivery systems for use in applications that include clinic trials. However, to
      compete with viral vectors for systemic delivery in vivo, their efficiencies and
      pharmacokinetics need to be improved. The addition of poly (ethylene glycol)
      lipids (PEGylation) prolongs circulation lifetimes of liposomes, but inhibits
      cellular uptake and endosomal escape of CL-DNA complexes. We show that this
      limits their transfection efficiency (TE) in a manner dependent on the amount of
      PEG-lipid, the lipid/DNA charge ratio, and the lipid membrane charge density. To
      improve endosomal escape of PEGylated CL-DNA complexes, we prepared an acid
      labile PEG-lipid (HPEG2K-lipid, PEG MW 2000) which is designed to lose its PEG
      chains at the pH of late endosomes. The HPEG2K-lipid and a similar but acid
      stable PEG-lipid were used to prepare PEGylated CL-DNA complexes. TLC and dynamic
      light scattering showed that HPEG2K-CL-DNA complexes are stable at pH 7.4 for
      more than 24 h, but the PEG chains are cleaved at pH 5 within 1 h, leading to
      complex aggregation. The acid-labile HPEG2K-CL-DNA complexes showed enhanced TE
      over complexes stabilized with the acid-stable PEG-lipid. Live-cell imaging
      showed that both types of complexes were internalized to quantitatively similar
      particle distributions within the first 2 h of incubation with cells. Thus, we
      attribute the increased TE of the HPEG2K-CL-DNA complexes to efficient endosomal
      escape, enabled by the acid-labile HPEG2K-lipid which sheds its PEG chains in the
      low pH environment of late endosomes, effectively switching on the electrostatic
      interactions that promote fusion of the membranes of complex and endosome.

PMID- 22469294
TI  - Surface conjugation of triphenylphosphonium to target poly(amidoamine) dendrimers
      to mitochondria.
AB  - Dendrimers have emerged as promising carriers for the delivery of a wide variety
      of pay-loads including therapeutic drugs, imaging agents and nucleic acid
      materials into biological systems. The current work aimed to develop a novel
      mitochondria-targeted generation 5 poly(amidoamine) (PAMAM) dendrimer (G(5)-D).
      To achieve this goal, a known mitochondriotropic ligand triphenylphosphonium
      (TPP) was conjugated on the surface of the dendrimer. A fraction of the cationic
      surface charge of G(5)-D was neutralized by partial acetylation of the primary
      amine groups. Next, the mitochondria-targeted dendrimer was synthesized via the
      acid-amine-coupling conjugation reaction between the acid group of (3
      carboxypropyl)triphenyl-phosphonium bromide and the primary amines of the
      acetylated dendrimer (G(5)-D-Ac). These dendrimers were fluorescently labeled
      with fluorescein isothiocyanate (FITC) to quantify cell association by flow
      cytometry and for visualization under confocal laser scanning microscopy to
      assess the mitochondrial targeting in vitro. The newly developed TPP-anchored
      dendrimer (G(5)-D-Ac-TPP) was efficiently taken up by the cells and demonstrated
      good mitochondrial targeting. In vitro cytotoxicity experiments carried out on
      normal mouse fibroblast cells (NIH-3T3) had greater cell viability in the
      presence of the G(5)-D-Ac-TPP compared to the parent unmodified G(5)-D. This
      mitochondria-targeted dendrimer-based nanocarrier could be useful for imaging as
      well as for selective delivery of bio-actives to the mitochondria for the
      treatment of diseases associated with mitochondrial dysfunction.

PMID- 22469295
TI  - A gene nanocomplex conjugated with monoclonal antibodies for targeted therapy of
      hepatocellular carcinoma.
AB  - To enhance tumor-targeting abilities and therapeutic efficiency, a monoclonal
      antibody-conjugated gene nanocomplex was herein designed. The biodegradable
      cationic polyethylenimine-grafted-alpha,beta-poly(N-3-hydroxypropyl)-DL
      aspartamide (PHPA-PEI) was used for complexing pDNA to form the PHPA-PEI/pDNA
      nanoparticle, and then 9B9 mAb, an anti-epidermal growth factor receptor (anti
      EGFR) monoclonal antibody, was conjugated to produce the PHPA-PEI/pDNA/9B9 mAb
      (PP9mN) complex. The PP9mN complex with the diameter of around 300 nm at its
      optimal weight ratio could be uptaken effectively by SMMC-7721 cells. The
      cytotoxicity of the PP9mN complex was much lower than that of PEI 25 kD in SMMC
      7721, HepG2, Bel-7404 and COS-7 cell lines. The PP9mN complex possessed the
      highly efficient in vitro gene delivery ability to the hepatocellular carcinoma
      cells. The in vivo gene expression indicated that PP9mN could target to the tumor
      tissues effectively. By using the therapeutic AChE gene, it was found that the
      PP9mN complexes significantly enhanced the anti-tumor effect on tumor-bearing
      nude mice. Such monoclonal antibody-conjugated gene complex should have great
      potential applications in liver cancer therapy.

PMID- 22469296
TI  - Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal
      contraceptives.
AB  - BACKGROUND: It takes many years to obtain reliable values for the risk of venous
      thrombosis of hormonal contraceptive users from clinical data. Measurement of
      activated protein C (APC) resistance via thrombin generation is a validated test
      for determining the thrombogenicity of hormonal contraceptives. Sex hormone
      binding globulin (SHBG) might serve as a marker for the risk of venous
      thrombosis, and can be easily and rapidly measured in routine laboratories.
      OBJECTIVE: To determine whether SHBG is a useful marker for the thrombotic risk
      of hormonal contraceptive users by comparing plasma SHBG levels with normalized
      APC sensitivity ratio (nAPCsr) values and thrombosis risks reported in the recent
      literature. METHODS: We conducted an observational study in 262 users of
      different contraceptives, and measured nAPCsr and SHBG levels. RESULTS: Users of
      contraceptives with a higher risk of causing venous thrombosis, i.e. combined
      hormonal contraceptives containing desogestrel, cyproterone acetate or
      drospirenone, and the transdermal patch, had higher SHBG levels than users of
      combined hormonal contraceptives containing levonorgestrel, which carry a lower
      thrombosis risk. Users of the patch had the highest SHBG levels, with a mean
      difference of 246 nmol L(-1) (95% confidence interval 179-349) from that in users
      of levonorgestrel-containing combined hormonal contraceptives. SHBG levels were
      positively associated with both the nAPCsr and the risks of venous thrombosis
      reported in the recent literature. CONCLUSION: SHBG is a useful marker with which
      to estimate the thrombotic safety of a preparation.

PMID- 22469297
TI  - Analysis of biodistribution and engraftment into the liver of genetically
      modified mesenchymal stromal cells derived from adipose tissue.
AB  - Presently, orthotopic liver transplant is the major therapeutic option for
      patients affected by primary liver diseases. This procedure is characterized by
      major invasive surgery, scarcity of donor organs, high costs, and lifelong
      immunosuppressive treatment. Transplant of hepatic precursor  cells represents an
      attractive alternative. These cells could be used either for allogeneic
      transplantation or for autologous transplant after ex vivo genetic modification.
      We used stromal cells isolated from adipose tissue (AT-SCs) as platforms for
      autologous cell-mediated gene therapy. AT-SCs  were transduced with lentiviral
      vectors expressing firefly luciferase, allowing for transplanted cell tracking by
      bioluminescent imaging (BLI). As a complementary approach, we followed
      circulating human alpha1-antitrypsin (hAAT) levels after infusion of AT-SCs
      overexpressing hAAT. Cells  were transplanted into syngeneic mice after CCl(4)
      induced hepatic injury. Luciferase bioluminescence signals and serum hAAT levels
      were measured at different time points after transplantation and demonstrate
      persistence of transplanted cells for up to 2 months after administration.  These
      data, along with immunohistochemical analysis, suggest engraftment and
      repopulation of injured livers by transplanted AT-SCs. Moreover, by
      transcriptional targeting using cellular tissue-specific regulatory sequences, we
      confirmed that AT-SCs differentiate towards a hepatogenic-like  phenotype in
      vitro and in vivo. Additionally, in transplanted cells reisolated from recipient
      animals' livers, we detected activation of the alpha-fetoprotein (AFP) promoter.
      This promoter is normally transcriptionally silenced in adult tissues but can be
      reactivated during liver regeneration,  suggesting commitment towards hepatogenic
      like differentiation of engrafted cells in vivo. Our data support AT-SC-mediated
      gene therapy as an innovative therapeutic option for disorders of liver
      metabolism.

PMID- 22469298
TI  - Photodynamic inactivation of methylene blue and tungsten-halogen lamp light
      against food pathogen Listeria monocytogenes.
AB  - The aim of this study was to verify the bactericidal effect and the damage of
      photodynamic inactivation (PDI) using methylene blue (MB) and tungsten-halogen
      lamp over Listeria monocytogenes via atomic force microscopy, absorption
      spectrophotometry, agarose gel electrophoresis, real-time PCR and SDS-PAGE. The
      obtained data indicated that the viability of L. monocytogenes was ca 7-log
      reduced by illumination with 10 min tungsten-halogen lamp light under the
      presence of 0.5 MUg mL(-1) MB, and this bactericidal activity against L.
      monocytogenes of PDI increased proportionally to the concentration of MB and the
      duration of irradiation. Moreover, after irradiation with MB and visible light,
      the leakage of intracellular contents was estimated by spectrophotometer at
      OD(260) and OD(280), which correlated with morphological alterations.
      Furthermore, genomic DNA cleavage and protein degradation were also detected
      after PDI treatment. Consequently, breakage of the membrane, damage of the
      genomic DNA and degradation of bacterial proteins may play an important role in
      the mechanisms involved in PDI-MB bactericidal activity on L. monocytogenes.

PMID- 22469299
TI  - Bilateral disease and early age at presentation are associated with shorter
      survival in patients with congenital heart disease and intraluminal pulmonary
      vein stenosis.
AB  - PURPOSE: Pulmonary vein stenosis (PVS) is a progressive disease that is
      frequently lethal. We have previously identified neoproliferation of
      myofibroblasts as the mechanism for progressive intraluminal PVS. PVS occurs in
      association with other congenital heart diseases (CHD) and in structurally normal
      hearts. This study sought to describe the spectrum of CHD seen with PVS and
      explore risk factors associated with mortality. METHODS: All patients diagnosed
      over a 12-year period with a combination of PVS involving >=2 vessels and CHD
      were identified. Cases were categorized according to major anatomic and
      physiologic categories. Patient and disease characteristics associated with time
      to death were explored. RESULTS: Eighty-two cases followed longitudinally at our
      institution were analyzed. Anatomic diagnoses included nonheterotaxy + anomalous
      pulmonary venous return (29%), heterotaxy + anomalous veins (20%), two ventricles
      + normal veins (22%), and single ventricle + normal veins (29%). Median age at
      diagnosis was 5.3 months (0-24 years). Despite multiple treatments, there were 35
      (43%) deaths in the group with an estimated survival of 71%, 64%, and 44% at 1,
      2, and 5 years, respectively. Bilateral disease at diagnosis (hazard ratio [HR]
      3.9 [1.7, 9.2], P= .002), age <5 months at diagnosis (HR 3.4 [1.6, 7.6], P=
      .002), and involvement of >2 pulmonary veins at diagnosis (HR 3.7 [1.6, 8.8], P=
      .003) were associated with shorter time to death in univariate analysis. In
      multivariable analysis, both bilateral disease (HR 2.9 [1.2, 7.1]P= .02) and age
      <5 months at diagnosis (HR 2.4 [1.1, 5.6]P= .03) were independently associated
      with time to death. CONCLUSION: Bilateral disease and earlier age at diagnosis
      are independent predictors of poor survival in patients with CHD and PVS, while
      patients with unilateral disease presenting at an older age have a better
      prognosis. These findings are helpful in risk stratification of patients with CHD
      and multivessel PVS.

PMID- 22469300
TI  - Less common clinical manifestations of atopic dermatitis: prevalence by age.
AB  - The common manifestations of atopic dermatitis (AD) appear sequentially with
      involvement of the cheeks in infancy, flexural extremities in childhood, and
      hands in adulthood. Although less common clinical manifestations are well
      described, they have not been the subject of epidemiologic studies to describe
      their prevalence in specific age groups. This observational, cross-sectional,
      comparative study included 131 children younger than 18 of both sexes with AD who
      attended the clinics of the Dermatology Department of the National Institute of
      Pediatrics in Mexico City. Patients were examined to determine the presence of
      infrequent clinical manifestations of AD during infancy, preschool and school
      age, and adolescence and stratified according to sex, age, and number of clinical
      signs. A chi-square test was used to detect differences according to age and sex.
      Logistic regression analysis was also performed. The main findings according to
      age were genital dermatitis and papular-lichenoid dermatitis variant in infants;
      atopic feet, prurigo-like, nummular pattern, and erythroderma in preschool and
      school-aged children; and eyelid eczema and nipple dermatitis in adolescents. The
      risk of development of nipple dermatitis and eyelid eczema increased with age,
      and the development of genital dermatitis decreased with age. The knowledge of
      the prevalence of less common clinical manifestations of AD according to age in
      different populations might be helpful in diagnosing incipient cases of AD.

PMID- 22469301
TI  - Commentary: revision lumbar surgery and revisiting the role of preoperative
      depression screening.
AB  - COMMENTARY ON: Adogwa O, Parker SL, Shau DN, et al. Preoperative Zung Depression
      Scale predicts outcome after revision lumbar surgery for adjacent segment
      disease, recurrent stenosis, and pseudarthrosis. Spine J 2012;12:179-85 (in this
      issue).

PMID- 22469302
TI  - Commentary: lessons and limitations of population-based research.
AB  - COMMENTARY ON: Battie MC, Jones CA, Schopflocher DP, Hu RW. Health-related
      quality of life and comorbidities associated with lumbar spinal stenosis. Spine J
      2012;12:189-95 (in this issue).

PMID- 22469303
TI  - Commentary: complications in spine surgery: "the devil is in the details".
AB  - COMMENTARY ON: Lee MJ, Konodi MA, Cizik AM, et al. Risk factors for medical
      complication after spine surgery: a multivariate analysis of 1,591 patients.
      Spine J 2012;12:197-206 (in this issue).

PMID- 22469304
TI  - Commentary: is bilateral pedicle screw fixation necessary when performing a
      transforaminal lumbar interbody fusion? An analysis of clinical outcomes,
      radiographic outcomes, and cost.
AB  - COMMENTARY ON: Xue H, Tu Y, Cai M. Comparison of unilateral versus bilateral
      instrumented transforaminal lumbar interbody fusion in degenerative lumbar
      diseases. Spine J 2012;12:209-15 (in this issue).

PMID- 22469305
TI  - Effect of short-term unloading on T2 relaxation time in the lumbar intervertebral
      disc--in vivo magnetic resonance imaging study at 3.0 tesla.
AB  - BACKGROUND CONTEXT: Diurnal changes in T2 values, indicative for changes in water
      content, have been reported in the lumbar intervertebral discs. However, data
      concerning short-term T2 changes are missing. PURPOSE: The purpose of this study
      was to investigate the short-term effects of unloading on T2 values in lumbar
      intervertebral discs in vivo. STUDY DESIGN: Experimental study with repeated
      measurements of lumbar discs T2 relaxation time during a period of 38 minutes of
      supine posture. PATIENT SAMPLE: Forty-one patients with acute or chronic low back
      pain (visual analog scale >=3). OUTCOME MEASURES: T2 relaxation time in the
      intervertebral disc, lumbar lordosis angle, and intervertebral disc height.
      METHODS: Forty-one patients (mean age, 41.6 years) were investigated in the
      supine position using a 3-tesla magnetic resonance system. Sagittal T2 mapping
      was performed immediately after unloading and after a mean delay of 38 minutes.
      No patient movement was allowed between the measurements. One region of interest
      (ROI) was manually placed in both the anterior and the posterior annulus fibrosus
      (AF) and three ROIs in the nucleus pulposus (NP). RESULTS: There was a
      statistically significant decrease in the anterior NP (-2.7 ms; p<.05) and an
      increase in T2 values in the posterior AF (+3.5 ms; p<.001). Discs with initially
      low T2 values in the NP showed minor increase in the posterior AF (+1.6 ms;
      p<.05), whereas a major increase in the posterior AF was found in discs with
      initially high T2 values in the NP (+6.8 ms; p=.001). Patients examined in the
      morning showed no differences, but those investigated in the afternoon showed a
      decrease in the anterior NP (-5.3 ms; p<.05) and an increase in the posterior AF
      (+7.8 ms; p=.002). No significant differences were observed in other regions.
      Correlation analysis showed moderate correlations between the time of
      investigation and T2 changes in the posterior AF (r=0.46; p=.002). CONCLUSIONS: A
      shift of water from the anterior to the posterior disc regions seems to occur
      after unloading the lumbar spine in the supine position. The clinical relevance
      of these changes needs to be investigated.

PMID- 22469306
TI  - Dural repairs with spinal sealants.

PMID- 22469309
TI  - Promoting wellness is achievable in rehabilitation--but what are the critical
      ingredients for success?

PMID- 22469310
TI  - Splenic artery ligation: A protection against hepatic ischemia/reperfusion injury
      in partially hepatectomized rats.
AB  - AIM:   In liver resection, the temporary occlusion of the hepatoduodenal ligament
      (Pringle maneuver) is often used. However, the maneuver causes
      ischemia/reperfusion (I/R) injury in the remnant liver. Heme oxygenase (HO)-1 has
      a cytoprotective role against this injury. Our aim is to investigate whether
      splenic artery ligation induces HO-1 expression in the liver and ameliorates the
      hepatic I/R injury in partially hepatectomized rats. METHODS:   Rats underwent
      splenic artery ligation by occluding the main splenic artery. Two days later, the
      total hepatic ischemia (Pringle maneuver) was conducted, and then a two-thirds
      partial hepatectomy (PH) was performed just before the start of reperfusion. HO
      inhibitor was twice injected s.c. at 3 and 16 h before the Pringle maneuver. HO-1
      levels were determined by western blotting. Liver injury was biochemically
      assessed. RESULTS:   In normal rats, HO-1 was highly expressed in the spleen, but
      not in the liver. Splenic artery ligation induced HO-1 in the livers. When rats
      underwent 20 and 30 min of Pringle maneuver/PH, survival rates were 28% and 8%,
      respectively. Splenic artery ligation significantly improved both the survival
      rates: 73% and 56%, respectively. Under these conditions, administration of HO-1
      inhibitor at least partly negated the efficacy of splenic artery ligation.
      Splenic artery ligation also increased the recovery rate of the remnant liver
      mass and platelet counts in Pringle maneuver/PH-treated rats. CONCLUSION:  
      Splenic artery ligation was significantly effective on the hepatic I/R injury in
      partially hepatectomized rats. Induction of HO-1 may be at least partly involved
      in the improvement of this injury.

PMID- 22469311
TI  - Relationship between swallowing problems and tooth loss in community-dwelling
      independent elderly adults: the Fujiwara-kyo study.
AB  - OBJECTIVES: To investigate the relationship between swallowing problems and the
      number of remaining teeth in healthy elderly people. DESIGN: Cross-sectional.
      SETTING: Nara, Japan. PARTICIPANTS: Three thousand six hundred sixty-three male
      and female volunteers aged 65 and older who were living independently were
      analyzed. MEASUREMENTS: Swallowing problems were defined operationally using a
      questionnaire and the 30-mL water swallow test. Data were collected on the number
      of remaining teeth, maximum bite force, occlusal status, presence or absence of
      oral dryness, and medical history. RESULTS: The prevalence of swallowing problems
      was 15.1% (n = 554) in this population. A positive correlation was observed
      between the number of remaining teeth and maximum bite force. The number of
      remaining teeth was categorized according to tertiles. Multiple logistic
      regression analysis revealed that the adjusted odds ratios for 0 to 13 or 14 to
      24 remaining teeth to 25 to 32 remaining teeth for swallowing problems were 2.04
      (95% confidence interval (CI) = 1.60-2.60) and 1.31 (95% CI = 1.02-1.70),
      respectively. Significant increases in these odds ratios were found in a trend
      test (P < .001). CONCLUSION: Tooth loss is associated with swallowing problems.
      Having fewer teeth inhibits masticatory ability, which disturbs the execution of
      smooth swallowing. Preventive measures against tooth loss at a younger age may be
      effective at reducing the risk of laryngeal penetration and aspiration at an
      older age.

PMID- 22469313
TI  - Bartonella spp. in rats and zoonoses, Los Angeles, California, USA.
AB  - Bartonella spp. were detected in rats (Rattus norvegicus) trapped in downtown Los
      Angeles, California, USA. Of 200 rats tested, putative human pathogens, B.
      rochalimae and B. tribocorum were found in 37 (18.5%) and 115 (57.5%) rats,
      respectively. These bacteria among rodents in a densely populated urban area are
      a public health concern.

PMID- 22469312
TI  - Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects.
AB  - AIMS: Lipopolysaccharide (LPS) is a TLR4 agonist which activates NFkappaB
      dependent cytokine production. We investigated LPS inhalation in healthy smokers
      as a model of COPD bacterial exacerbations. We studied safety, reproducibility,
      the translocation of the NFkappaB subunit p65 in sputum cells and changes in
      systemic biomarkers of inflammation. METHODS: Twelve smokers inhaled 5 and 30 ug
      LPS and safety was monitored over 24 h. IL-6, CRP, CCl-18, SP-D, CC-16 and beta
      defensin 2 were measured in serum samples collected at baseline, 4, 8 and 24 h.
      Sputum was induced at baseline, 6 and 24 h for cell counts and p65 expression.
      Repeated challenges were performed after a 2 week interval in 10 smokers.
      RESULTS: LPS inhalation was well tolerated. Significant increases occurred in
      sputum neutrophil counts with both doses, with a maximum increase of 21.5% at 6 h
      after 30 ug which was reproducible, r(i ) (intraclass correlation coefficient) =
      0.88. LPS increased sputum cell nuclear p65 translocation and phospho-p65
      expression. All of the serum biomarkers increased following challenge but with
      different temporal patterns. DISCUSSION: Inhaled LPS challenge in smokers causes
      pulmonary and systemic inflammation that involves NFkappaB activation. This
      appears to be a suitable model for studying bacterial exacerbations of COPD.

PMID- 22469314
TI  - Rickettsia monacensis as cause of Mediterranean spotted fever-like illness,
      Italy.

PMID- 22469315
TI  - Aripiprazole: polymorphs and solvatomorphs.

PMID- 22469316
TI  - Amlodipine besylate.

PMID- 22469317
TI  - Candesartan cilexetil.

PMID- 22469318
TI  - Flurbiprofen.

PMID- 22469319
TI  - Gatifloxacin.

PMID- 22469320
TI  - Lamotrigine.

PMID- 22469321
TI  - Pimozide.

PMID- 22469322
TI  - Risperidone.

PMID- 22469323
TI  - Sunitinib malate.

PMID- 22469324
TI  - Varenicline.

PMID- 22469326
TI  - Validation of analytical methods-update 2011.

PMID- 22469325
TI  - Zolpidem tartrate.

PMID- 22469329
TI  - The relationship between body composition and fracture risk using the FRAX model
      in central south Chinese postmenopausal women.
AB  - OBJECTIVES: To assess the relationship between body composition and fracture risk
      as determined by the FRAX((r))  model in postmenopausal women in central south
      China. METHODS: A cross-sectional study was conducted in 779 women. Bone mineral
      density (BMD) of the left femur and total body composition were measured by dual
      X-ray absorptiometry. All clinical information was available for incorporation
      into the FRAX model to assess the 10-year fracture probability. RESULTS: In the
      FRAX model, when BMD values were included, the 10-year probability of major
      osteoporotic fractures and hip fractures was 3.4% and 1.0%, respectively, which
      was significantly higher than the probability rates of 2.7% and 0.8%,
      respectively, for the same events when BMD values were not included (P < 0.01).
      Both fat mass and lean mass were negatively correlated with the predicted 10-year
      probability of fracture (P < 0.01), and femoral neck BMD was the most significant
      determinant of the predicted 10-year fracture probability. Compared with fat
      mass, lean mass had more impact on the 10-year probability of both major and hip
      osteoporotic fractures. CONCLUSION: In postmenopausal women in central south
      China, both fat mass and lean mass were negatively correlated with the predicted
      10-year fracture probability. The effect of lean mass and fat mass on fracture
      risk may be mediated through their impact on BMD. Compared with fat mass, lean
      mass had more of an impact on the risk of both major osteoporotic and hip
      fractures, showing that physical activity is an important component in the
      prevention of osteoporotic fracture.

PMID- 22469330
TI  - A preliminary study on the relationships between global health/quality of life
      and specific head and neck cancer quality of life domains in Puerto Rico.
AB  - PURPOSE: Health-related quality of life (HRQOL) is an important treatment outcome
      for head and neck cancer (HNC) patients. By ascertaining the most important HNC
      HRQOL issues, research and practice can be directed toward enhancing patient QOL.
      MATERIALS AND METHODS: A cross-sectional study of 46 ENT clinic HNC patients in
      Puerto Rico (PR) was completed. The European Organization for Research and
      Treatment of Cancer (EORTC) QLQ-C30 (general QOL), and the QLQ-H&N35 (HNC QOL)
      instruments were administered. Correlations and multivariable regressions were
      separately conducted for QLQ-H&N35 variables on the three QLQ-C30 outcome
      variables: overall health, overall QOL, and the global health/QOL domain.
      RESULTS: Correlation findings included statistically significant negative
      correlations between the three QLQ-C30 outcome variables and the QLQ-H&N35
      variables pain, swallowing, social eating, social contact, and sexuality.
      Multivariable linear regression identified statistically significant inverse
      indicators of the outcomes: (1) "lessening of sexuality" with "overall health"
      (p= 0.02), (2) "problem with social eating" (p= 0.023), "taking pain killers" (p=
      0.025), and "problem with social contact" (p= 0.035) with "overall QOL," and (3)
      "problems with social eating" (p < 0.009) and "taking pain killers" (p= 0.016)
      with the "global health/QOL" domain. CONCLUSIONS: We conclude that problems with
      pain, social eating, social interactions, and loss of sexuality are critical
      indicators of degraded HRQOL in HNC patients living in Puerto Rico. Our results
      add to the overall knowledge base regarding QOL among HNC patients. The promise
      of improved QOL for the HNC patient is attainable through additional research in
      conjunction with advances in clinical treatments and patient management
      protocols.

PMID- 22469332
TI  - Taste disorders in myasthenia gravis: a multicenter cooperative study.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to investigate the
      prevalence and clinical characteristics of taste disorders in patients with
      myasthenia gravis (MG). METHODS: We studied 371 Japanese patients with MG (127
      men and 244 women; mean age, 56.6+/-16.9years) consecutively evaluated between
      May and September 2010 in six neurological centers comprising the East Japan MG
      Study Group. Ninety-three patients (25%) had thymoma. We interviewed all patients
      to determine whether they had taste disorders during the clinical course of MG
      and then further evaluated the patients with MG, who reported having taste
      disorders, using a questionnaire. RESULTS: Taste disorders were observed in 16
      (4.3%) of the 371 patients with MG. We concluded that taste disorders in 2.4% of
      patients with MG excluding other factors were associated with MG itself. All
      patients had thymoma with seropositivity for anti-acetylcholine receptor
      antibodies. Thymoma tended to be advanced, and four patients with Masaoka stage
      IVa required radiation therapy or chemotherapy. Five patients noticed taste
      disorders 2-3 months before the onset of MG. Sweet taste loss was more common
      than salty, bitter, and sour taste loss. CONCLUSIONS: This was the first
      systematic survey of taste disorders in patients with MG by a multicenter study.
      Taste disorders were more common in the present sample of patients with MG than
      in the general population.

PMID- 22469333
TI  - Antioxidant, antibacterial, cytotoxic, and apoptotic activity of stem bark
      extracts of Cephalotaxus griffithii Hook. f.
AB  - BACKGROUND: Cephalotaxus spp. are known to possess various therapeutic
      potentials. Cephalotaxus griffithii, however, has not been evaluated for its
      biological potential. The reason may be the remoteness and inaccessibility of the
      habitat where it is distributed. The main aim of this study was to: (1) evaluate
      multiple biological potentials of stem bark of C. griffithii, and (2) identify
      solvent extract of stem bark of C. griffithii to find the one with the highest
      specific biological activity. METHODS: Dried powder of stem bark of C. griffithii
      was exhaustively extracted serially by soaking in petroleum ether, acetone and
      methanol to fractionate the chemical constituents into individual fractions or
      extracts. The extracts were tested for total phenolic and flavonoid content,
      antioxidant (DPPH radical scavenging, superoxide radical scavenging, and reducing
      power models), antibacterial (disc diffusion assay on six bacterial strains),
      cytotoxic (MTT assay on HeLa cells), and apoptotic activity (fluorescence
      microscopy, DNA fragmentation assay, and flow cytometry on HeLa cells). RESULTS:
      Among the three extracts of stem bark of C. griffithii, the acetone extract
      contained the highest amount of total phenolics and flavonoids and showed maximum
      antioxidant, antibacterial, cytotoxic (IC50 of 35.5 +/- 0.6 MUg/ml; P < 0.05),
      and apoptotic (46.3 +/- 3.6% sub-G0/G1 population; P < 0.05) activity, followed
      by the methanol and petroleum ether extracts. However, there was no significant
      difference observed in IC50 values (DPPH scavenging assay) of the acetone and
      methanol extracts and the positive control (ascorbic acid). In contrast,
      superoxide radical scavenging assay-based antioxidant activity (IC50) of the
      acetone and methanol extracts was significantly lower than the positive control
      (P < 0.05). Correlation analysis suggested that phenolic and flavonoid content
      present in stem bark of C. griffithii extracts was responsible for the high
      antioxidant, cytotoxic, and apoptotic activity (P < 0.05). CONCLUSIONS: Stem bark
      of C. griffithii has multiple biological effects. These results call for further
      chemical characterization of acetone extract of stem bark of C. griffithii for
      specific bioactivity.

PMID- 22469335
TI  - Dengue in patients with central nervous system manifestations, Brazil.
AB  - We investigated the prevalence of dengue in patients with suspected viral
      meningitis/meningoencephalitis in a dengue-endemic area. Cerebrospinal fluid
      analysis showed positive results and a 6.74* greater likelihood of identifying
      positive fluid in patients who died. Our findings support testing patients with
      neurologic manifestations for the virus in dengue-endemic areas.

PMID- 22469336
TI  - Cor triatriatum dexter versus prominent Eustachian valve in an adult congenital
      heart disease patient.
AB  - An eustachian valve (EV) remnant, if present, is usually noted by the presence of
      a thin ridge or a crescent-shaped fold of endocardium arising from the anterior
      rim of the inferior vena cava orifice due to the persistence of the right sinus
      venosus valve. Though the embryologic explanation of cor triatriatum dexter (CTD)
      is the same as that of the normal formation of the EV--lack of regression of the
      right sinus venosus valve--it is usually called CTD or divided right atrium when
      there are attachments on the atrial septum giving the appearance of a divided
      atrium. However, it's called prominent eustachian valve when the right sinus
      venosus valve has partly regressed, with no remaining septal attachments and
      without the appearance of a divided atrium. We present the case of an adult
      patient with an atrial septal defect with a high insertion of a giant EV, which
      mimics the echocardiographic appearance of divided right atrium.

PMID- 22469337
TI  - Skewed T-cell receptor beta chain variable gene (TCRBV) usage among different
      clinical types of patients with chronic HBV infection.
AB  - This study aimed to determine the degree of clonal expansion of T cells in
      peripheral blood mononuclear cells (PBMCs) isolated from patients suffering from
      different clinical types of hepatitis B (HB) infection and to analyse the
      clinical relevance of the skewed T-cell receptor beta variable (TCRBV). Sera and
      PBMCs were collected from 90 HB patients. Gene melting spectral pattern (GMSP)
      analysis was used to determine the distribution and expansion of populations
      expressing specific TCRBV complementary determined region 3 (CDR3) genes. TCRBV
      genes associated with monoclonal expansion were sequenced. TCRBV families from
      the majority of patients (80/90) displayed skewed T-cell expansion. Furthermore,
      TCRBV11, BV12 and BV13.1 were more frequent than other TCRBV genes; the sequence
      of TCRBV11 CDR3 was expressed as 'VYNEQ' in all patients and was accompanied by
      the BJ2.1 fragment. In patients with chronic HB, the frequency of skewed TCRBV
      was inversely correlated with hepatitis B virus (HBV) DNA levels. The
      persistently skewed TCRBV gene families in HB patients may be associated with the
      development and maintenance of hepatitis. GMSP analysis of TCRBV gene families
      may be helpful in estimating disease status, and BV11 may be associated with HBV
      replication in patients with chronic HBV infection.

PMID- 22469338
TI  - Visualizing context through theory deconstruction: a content analysis of three
      bodies of evaluation theory literature.
AB  - While the evaluation field collectively agrees that contextual factors bear on
      evaluation practice and related scholarly endeavors, the discipline does not yet
      have an explicit framework for understanding evaluation context. To address this
      gap in the knowledge base, this paper explores the ways in which evaluation
      context has been addressed in the practical-participatory, values-engaged, and
      emergent realist evaluation literatures. Five primary dimensions that constitute
      evaluation context were identified for this purpose: (1) stakeholder; (2)
      program; (3) organization; (4) historical/political; and (5) evaluator. Journal
      articles, book chapters, and conference papers rooted in the selected evaluation
      approaches were compared along these dimensions in order to explore points of
      convergence and divergence in the theories. Study results suggest that the
      selected prescriptive theories most clearly explicate stakeholder and evaluator
      contexts. Programmatic, organizational, and historical/political contexts, on the
      other hand, require further clarification.

PMID- 22469339
TI  - Seeing voices of health disparity: evaluating arts projects as influence
      processes.
AB  - Arts-informed approaches are increasingly popular as vehicles for research,
      knowledge translation and for engaging key stakeholders on topics of health and
      health care. This paper describes an evaluation of a multimedia art installation
      intended to promote awareness of health disparities as experienced by homeless
      persons living in Toronto (Canada). The objective of the evaluation was to
      determine whether the installation had an impact on audience members, and if so,
      to understand its influence on viewers' perspectives on homelessness and the
      health concerns of homeless persons. Key themes were identified through the
      analysis of direct observational data of viewer interactions with the exhibit and
      qualitative interviews with different audience members after the exhibit. The
      four key themes were: (1) Promoting recognition of common humanity between
      viewers and viewed (challenging previously held assumptions and stereotypes,
      narrowing perceived social distance); (2) functions fulfilled (or potentially
      fulfilled) by the exhibit: raising awareness, educational applications, and
      potential pathways by which the exhibit could serve as a call to social action;
      (3) stories that prompt more stories: the stories within the exhibit (coupled
      with the interview questions) prompted further sharing of stories amongst the
      evaluation respondents, highlighting the iterative nature of such approaches.
      Respondents told of recognizing similarities in the experiences recounted in the
      exhibit with their own interactions with homeless persons; (4) strengths and
      weaknesses identified: including aesthetic features, issues of audience 'reach'
      and the importance of suitable venues for exhibition. Theoretically informed by
      narrative analysis and visual anthropology, this evaluation demonstrates that
      arts-informed 'interventions' are highly complex and work in subtle ways on
      viewers, allowing them to re-imagine the lives of others and identify points of
      common interest. It also problematizes our assumptions about which outcomes
      matter and why.

PMID- 22469340
TI  - The case for spatial analysis in evaluation to reduce health inequities.
AB  - The article begins by giving an overview of spatial thinking concepts that are
      relevant to evaluation. The article relates the spatial perspective to both a
      realist evaluation and a randomized control trial perspective in evaluation to
      demonstrate the benefits of a spatialized program and evaluation perspective. The
      article mainly suggests that the adoption of a spatial perspective can add new
      insights to the theory and practice of evaluation in ways that helps evaluation
      move closer to reducing health inequities.

PMID- 22469341
TI  - What can practitioners learn from theorists' logic models?
AB  - In response to previous papers in this issue, I consider the ways that logic
      models of evaluation theories may improve practice. Our conceptions of how theory
      informs practice are colored by who we have in mind when we speak of
      practitioners and theorists. I offer working definitions of these roles. It is
      also colored by the process we imagine connects theory to practice. I present a
      theory-based explanation of the factors that may shape practice and describe how
      theorists, using logic models, may be able to exploit these factors to promote
      the use of their theories. Throughout, I argue that theorists are primarily
      responsible for the proper use of their theories just as evaluators are primarily
      responsible for the proper use of their evaluations. This responsibility is best
      fulfilled in collaboration with the larger community of evaluators. Recent
      methods and software allow theorists to conduct large-scale theory-building
      collaborations that are organized around logic models. I discuss the benefits
      these advances may have for the field.

PMID- 22469342
TI  - Education and patient care effects of resident workload restrictions: tackling a
      largely unexplored subject.

PMID- 22469343
TI  - Complexity science to conceptualize health and disease: is it relevant to
      clinical medicine?

PMID- 22469344
TI  - Service census caps and unit-based admissions: resident workload, conference
      attendance, duty hour compliance, and patient safety.
AB  - OBJECTIVE: To examine the effect of census caps and unit-based admissions on
      resident workload, conference attendance, duty hour compliance, and patient
      safety. PARTICIPANTS AND METHODS: We implemented a census cap of 14 patients on 6
      Mayo Clinic internal medicine resident hospital services and a unit-based
      admissions process in which patients and care teams were consolidated within
      hospital units. All 280 residents and 15,926 patient admissions to resident and
      nonresident services 1 year before the intervention (September 1, 2006, through
      August 31, 2007) and 1 year after the intervention (May 1, 2008, through April
      30, 2009) were included. Residents' workload, conference attendance, and duty
      hours were tracked electronically. Patient safety variables including Rapid
      Response Team and cardiopulmonary resuscitation events, intensive care unit
      transfers, Patient Safety Indicators, and 30-day readmissions were compared
      preintervention and postintervention. RESULTS: After the intervention, residents'
      mean (SE) ratings of workload appropriateness improved (3.10 [0.08] vs 3.87
      [0.08] on a 5-point scale; P<.001), as did conference attendance (1523 [56. 8%]
      vs 1700 [63.5%] conferences attended; P<.001). Duty hour violations for working
      more than 30 consecutive hours and not having 10 hours off between duty periods
      decreased from 77 of 9490 possible violations (0.81%) to 27 (0.28%) and from 70
      (0.74%) to 14 (0.15%) violations, respectively (both, P<.001). Thirty-day
      readmissions to resident services decreased (1010 [18.14%] vs 682 [15. 37%];
      P<.001). All other patient safety measures remained unchanged. After adjustment
      for illness severity, there were no significant differences in patient outcomes
      between resident and nonresident services. CONCLUSION: Census caps and unit-based
      admissions were associated with improvements in resident workload, conference
      attendance, duty hour compliance, and readmission rates while patient outcomes
      were maintained.

PMID- 22469345
TI  - Increasing incidence of melanoma among young adults: an epidemiological study in
      Olmsted County, Minnesota.
AB  - OBJECTIVE: To identify the change in the incidence of cutaneous melanoma over
      time among young adults. PATIENTS AND METHODS: Using Rochester Epidemiology
      Project data, we identified patients aged 18 to 39 years who had a first lifetime
      diagnosis of melanoma from January 1, 1970, through December 31, 2009, in Olmsted
      County, Minnesota. Demographic and clinical information, including survival, was
      abstracted, and estimates of the incidence of melanoma and overall and disease
      specific survival were generated. RESULTS: From 1970 to 2009, the incidence of
      melanoma increased by 8-fold among young women and 4-fold among young men.
      Overall and disease-specific survival seemed to improve over time; hazard ratios
      comparing year of diagnosis with mortality were 0.92 and 0.91, respectively.
      CONCLUSION: The incidence of cutaneous melanoma among young adults is rapidly
      increasing, especially among women. Continued close monitoring of this high-risk
      population is necessary.

PMID- 22469346
TI  - High school football and risk of neurodegeneration: a community-based study.
AB  - OBJECTIVE: To assess whether high school football played between 1946 and 1956,
      when headgear was less protective than today, was associated with development of
      neurodegenerative diseases later in life. METHODS: All male students who played
      football from 1946 to 1956 in the high schools of Rochester, Minnesota, plus a
      non-football-playing referent group of male students in the band, glee club, or
      choir were identified. Using the records-linkage system of the Rochester
      Epidemiology Project, we reviewed (from October 31, 2010, to March 30, 2011) all
      available medical records to assess later development of dementia, Parkinson
      disease (PD), or amyotrophic lateral sclerosis (ALS). We also compared the
      frequency of dementia, PD, or ALS with incidence data from the general population
      of Olmsted County, Minnesota. RESULTS: We found no increased risk of dementia,
      PD, or ALS among the 438 football players compared with the 140 non-football
      playing male classmates. Parkinson disease and ALS were slightly less frequent in
      the football group, whereas dementia was slightly more frequent, but not
      significantly so. When we compared these results with the expected incidence
      rates in the general population, only PD was significantly increased; however,
      this was true for both groups, with a larger risk ratio in the non-football
      group. CONCLUSION: Our findings suggest that high school students who played
      American football from 1946 to 1956 did not have an increased risk of later
      developing dementia, PD, or ALS compared with non-football-playing high school
      males, despite poorer equipment and less regard for concussions compared with
      today and no rules prohibiting head-first tackling (spearing).

PMID- 22469347
TI  - Total knee arthroplasty outcomes in top-ranked and non-top-ranked orthopedic
      hospitals: an analysis of Medicare administrative data.
AB  - OBJECTIVE: To examine outcomes of Medicare enrollees who underwent primary total
      knee arthroplasty (TKA) in top-ranked orthopedic hospitals identified through the
      U.S. News & World Report hospital rankings and 2 comparison groups of hospitals.
      PATIENTS AND METHODS: We used Medicare Part A data to identify patients who
      underwent primary TKA between January 1, 2006, and December 31, 2006, in 3 groups
      of hospitals: (1) top-ranked according to U.S. News & World Report rankings; (2)
      not top-ranked, but eligible for ranking; and (3) not eligible for ranking by
      U.S. News & World Report. We compared the demographics and comorbidity of
      patients treated in the 3 hospital groups. We examined rates of postoperative
      adverse outcomes--a composite consisting of hemorrhage, pulmonary embolism, deep
      vein thrombosis, wound infection, myocardial infarction, or mortality within 30
      days of surgery. We also compared 30-day all-cause readmission rates and hospital
      length of stay (LOS) across groups. RESULTS: Our cohort consisted of 48 top
      ranked hospitals (performing 10,477 primary TKAs), 288 eligible non-top-ranked
      hospitals (28,938 TKAs), and 481 hospitals not eligible for ranking (25,297
      TKAs). Unadjusted rates of the composite outcome were modestly higher for top
      ranked hospitals (4.3%, 455 patients) as compared with non-top-ranked hospitals
      (4.1%, 1191 patients) and hospitals ineligible for ranking (3.3%, 843 patients)
      (P<.001), but these differences were no longer significant after accounting for
      differences in patient complexity. Likewise, there were no significant
      differences in readmission rates or LOS across groups. CONCLUSION: Rates of
      postoperative complications and readmission and hospital LOS were similar for
      Medicare patients who underwent primary TKA in top-ranked and non-top-ranked
      hospitals.

PMID- 22469349
TI  - The Creating Incentives and Continuity Leading to Efficiency staffing model: a
      quality improvement initiative in hospital medicine.
AB  - OBJECTIVE: To determine the effect of a hospitalist-developed, continuity
      centered hospitalist staffing model on patient outcomes and resource use.
      METHODS: The Creating Incentives and Continuity Leading to Efficiency (CICLE)
      staffing model was conceived by a group of hospitalists who sought to improve
      continuity of inpatient care. Using a retrospective, observational, pre-post
      study design, we compared patient-level data for all discharges from our
      hospitalist service from 6 months after implementation of the CICLE staffing
      model (September 1, 2009, through February 28, 2010; n=1585) with data from those
      same months in the prior year (September 1, 2008, through February 28, 2009;
      n=1808). We used the number of unique hospitalists who documented an encounter
      during the admission as a measure of continuity of care. Length of stay and
      hospital charges per admission constituted the measures of resource use. RESULTS:
      The odds of having a single hospitalist for the entire hospitalization nearly
      doubled under the CICLE model (odds ratio, 1.87; 95% confidence interval, 1.60
      2.2; P<.001). Mean length of stay decreased 7.5% (from 2.92 before to 2.70 days
      after initiation of the model; P<.001). Mean hospital charge per admission
      decreased 8.5% (from $7224.33 before to $6607.79 after initiation of the model;
      P<.001). Thirty-day readmission rates were not substantially affected by the
      CICLE model (15.0% before to 17.3% after initiation of the model; P=.08).
      CONCLUSION: Improved continuity of care among hospitalists was associated with
      reductions in length of stay and lower health care costs. These benefits were
      realized without substantially affecting readmission rates. The staffing model
      can be achieved by reorganizing existing hospitalists and may not require the
      hiring of additional personnel. The CICLE staffing model is a viable option for
      hospitalist groups that are aiming to diminish resource use and improve quality
      of care.

PMID- 22469348
TI  - Meta-analysis of randomized controlled trials of vancomycin for the treatment of
      patients with gram-positive infections: focus on the study design.
AB  - OBJECTIVE: To study the effectiveness and safety of vancomycin compared with that
      of other antibiotics for the treatment of gram-positive infections. METHODS:
      Major electronic databases were searched. Data from published randomized
      controlled trials (January 1, 1950, to September 15, 2011) were pooled using a
      meta-analytic method. RESULTS: Fifty-three trials comparing vancomycin with
      linezolid, daptomycin, quinupristin-dalfopristin, tigecycline, ceftaroline,
      ceftobiprole, telavancin, teicoplanin, iclaprim, and dalbavancin were included in
      the meta-analysis. Individual antibiotics were as effective as vancomycin, except
      for linezolid, which was more effective than vancomycin for the treatment of skin
      and soft tissue infections (odds ratio [OR], 1.61; 95% confidence interval [CI],
      1.07-2.43). Comparators were as effective as vancomycin in the intent-to-treat
      population (OR, 1.08; 95% CI, 0.98-1.18) but were more effective in the
      clinically evaluable population (OR, 1.14; 95% CI, 1.02-1.27) when all infections
      were pooled. When available data from all trials were pooled, no differences were
      noted when patients with febrile neutropenia (OR, 1.07; 95% CI, 0.82-1.39),
      pneumonia (OR, 1.10; 95% CI, 0.87-1.37), bacteremia (OR, 1.05; 95% CI, 0.76
      1.45), and skin and soft tissue infections (OR, 1.11; 95% CI, 0.89-1.39) were
      studied. Comparators were more effective in open-label (OR, 1.28; 95% CI, 1.08
      1.50) but not in double-blind trials (OR, 1.04; 95% CI, 0.90-1.20). Total adverse
      events attributed to studied antibiotics (OR, 1.07; 95% CI, 0.90-1.28) and
      patients withdrawn from trials (OR, 0.86; 95% CI, 0.68-1.09) were similar in the
      compared groups. Mortality was not different between vancomycin and comparator
      antibiotics when all trials were included in the analysis (OR, 1.09; 95% CI, 0.96
      1.23). Comparators were associated with higher mortality in open-label (OR, 1.27;
      95% CI, 1.05-1.54) but not double-blind trials (OR, 0.96; 95% CI, 0.80-1.14).
      CONCLUSION: On the basis mainly of data from open-label trials, vancomycin is a
      treatment choice that is as effective as other available antibiotics for patients
      with gram-positive infections. Study design seems to make a major contribution to
      the outcome.

PMID- 22469350
TI  - A comparison of general medical and clinical ethics consultations: what can we
      learn from each other?
AB  - Despite the emergence of clinical ethics consultation as a clinical service in
      recent years, little is known about how clinical ethics consultation differs
      from, or is the same as, other medical consultations. A critical assessment of
      the similarities and differences between these 2 types of consultations is
      important to help the medical community appreciate ethics consultation as a vital
      service in today's health care setting. Therefore, this Special Article presents
      a comparison of medical and clinical ethics consultations in terms of fundamental
      goals of consultation, roles of consultants, and methodologic approaches to
      consultation, concluding with reflections on important lessons about the
      physician-patient relationship and medical education that may benefit practicing
      internists. Our aim is to examine ethics consultation as a clinical service
      integral to the medical care of patients. Studies for this analysis were obtained
      through the PubMed database using the keywords ethics consultation, medical
      consultation, ethics consults, medical consults, ethics consultants, and medical
      consultants. All English-language articles published from 1970 through August
      2011 that pertained to the structure and process of medical and ethics
      consultation were reviewed.

PMID- 22469351
TI  - Clinical pharmacology, uses, and adverse reactions of iodinated contrast agents:
      a primer for the non-radiologist.
AB  - Iodinated contrast agents have been in use since the 1950s to facilitate
      radiographic imaging modalities. Physicians in almost all specialties will either
      administer these agents or care for patients who have received these drugs.
      Different iodinated contrast agents vary greatly in their properties, uses, and
      toxic effects. Therefore, clinicians should be at least superficially familiar
      with the clinical pharmacology, administration, risks, and adverse effects
      associated with iodinated contrast agents. This primer offers the non-radiologist
      physician the opportunity to gain insight into the use of this class of drugs.

PMID- 22469352
TI  - Nocardiosis: updates and clinical overview.
AB  - Nocardia, a gram-positive bacillus with the microscopic appearance of branching
      hyphae, can produce considerable disease in the appropriate host. The taxonomy of
      Nocardia continues to evolve; more than 50 species have been described. Early
      recognition and effective therapy are imperative to achieve successful outcomes.
      Although nocardiosis typically occurs in patients with cell-mediated
      immunosuppressive conditions, infection may occasionally develop in
      immunocompetent patients as well. This review addresses the microbiology of
      Nocardia, risk factors for infection, clinical presentations, and management
      strategies.

PMID- 22469353
TI  - 79-year-old woman with forgetfulness.

PMID- 22469354
TI  - Can vitamin D deficiency break your heart?

PMID- 22469355
TI  - Predicting recurrent depression using vitamin D levels?

PMID- 22469356
TI  - Sustained blood pressure-lowering actions of subcutaneous B-type natriuretic
      peptide (nesiritide) in a patient with uncontrolled hypertension.

PMID- 22469358
TI  - Multiple digital gangrene and polyuria.

PMID- 22469359
TI  - Adolf Butenandt--Nobel Prize for chemistry.

PMID- 22469361
TI  - Enhancing team learning in nursing teams through beliefs about interpersonal
      context.
AB  - AIM: This article is a report of a study that examines the relationship between
      team-level learning and performance in nursing teams, and the role of beliefs
      about the interpersonal context in this relationship. BACKGROUND: Over recent
      years, there has been an increasing interest in the learning processes of work
      teams. Researchers have investigated the impact of team learning on team
      performance, and the enabling conditions for this learning. However, team
      learning in nursing teams has been largely ignored. DESIGN: A cross-sectional
      field survey design was used. METHODS: The sample comprises a total of 468
      healthcare professionals working in 89 nursing teams at different public
      hospitals throughout Spain. Members of nursing teams participated voluntarily by
      completing a confidential individual questionnaire. Team supervisors evaluated
      nursing teams' performance. Data were collected over 2007-2008. RESULTS: The
      results show a mediating effect of team learning on the relationship between
      beliefs about interpersonal context (psychological safety, perceived task
      interdependence, and group potency) and team performance. CONCLUSION: Our
      findings suggest that beliefs about interpersonal context and team learning are
      important to effective nursing team performance.

PMID- 22469362
TI  - Age-related changes in the impact of contextual strength on multiple aspects of
      sentence comprehension.
AB  - Contextual information influences multiple aspects of language comprehension
      extended over time. To determine how age-related changes impact normal
      comprehension, effects of contextual strength were examined with event-related
      potentials. Increased contextual constraint facilitated semantic processing
      (reduced N400s). Effects were smaller and delayed for older adults, and
      sensitivity to contextual information was diminished for weak contexts. Both
      groups elicited a later left-lateralized frontal negativity associated with
      reinterpretation of context when multiple interpretations of a sentence were
      likely. Older adults evidenced the frontal negativity over a wider range of
      constraint. The change in the use of contextual information across age is
      attributed to decreased reliance on predictive processing for older adults. Thus,
      age-related changes in comprehension lead to differential engagement of
      processing resources over time for older adults.

PMID- 22469363
TI  - Skin toxicities and survival in advanced hepatocellular carcinoma patients
      treated with sorafenib.
AB  - AIM:   Sorafenib is the first small molecule with significant clinical activity
      for advanced hepatocellular carcinoma (HCC). However, intolerable adverse events
      are sometimes observed. On the other hand, it has been reported that some
      toxicities of molecular targeted drugs, such as skin toxicities and arterial
      hypertension, are correlated with good clinical outcomes in other cancers.
      METHODS:   We identified the correlations between adverse events and prognosis
      for sorafenib therapy in all patients with HCC treated at the institutions of the
      Saga Liver Cancer Study Group. The toxicities were assessed using the Common
      Terminology Criteria for Adverse Events version 4.0. RESULTS:   Ninety-four
      patients received sorafenib until August 2010. The overall incidence of treatment
      related adverse events was 98% of patients. Skin toxicities, including palmar
      plantar erythrodysesthesia syndrome, rash, pruritus and alopecia, were the most
      common adverse events and were observed in 58 patients (62%). Hypertension was
      observed in 23 patients (24%). The median survival time was 12.5 months among the
      total patients. The patients with skin toxicities showed significantly longer
      survival than the patients without these toxicities (hazard ratio, 0.449; 95%
      confidence interval, 0.256-0.786; P = 0.005). Hypertension had no correlation
      with survival. Skin toxicities were also significant prognostic factors in a
      multivariate analysis (hazard ratio, 0.522; 95% confidence interval, 0.274-0.997;
      P = 0.049), along with Child-Pugh class and alpha-fetoprotein level. The median
      development time for skin toxicities was 21 days. CONCLUSION:   Skin toxicities
      occur commonly at the early phase in patients treated with sorafenib, and could
      be a promising surrogate marker for the treatment outcome.

PMID- 22469364
TI  - Spectrum of central nervous system abnormalities in neurocutaneous melanocytosis.
AB  - AIM: Neurocutaneous melanocytosis is a rare neurocutaneous syndrome defined by
      the presence of large and/or multiple congenital cutaneous nevi and melanocytic
      deposits in the central nervous system. We sought to define the spectrum of
      central nervous system abnormalities in children with neurocutaneous
      melanocytosis. METHOD: We retrospectively reviewed cases of neurocutaneous
      melanocytosis referred to the pediatric neuro-oncology service at our center from
      2003 to 2010. RESULTS: Of 14 patients (11 males, 3 females) identified, eight
      were living. Median age of survivors was 31 months (range 12mo-6y 10mo) while
      median age of death was 81 months (19mo-28y). Of the six patients who died, all
      had diffuse leptomeningeal melanocytic deposits and four had leptomeningeal
      melanoma. All patients had neuroimaging: six had findings suggestive of diffuse
      leptomeningeal melanocytosis; seven had multifocal melanocytic deposits; and one
      patient had normal neuroimaging but focal seizures. Spinal abnormalities were
      common: three patients had extensive dorsal spinal arachnoid cysts and one had a
      benign cervical spindle cell tumor. Seven patients had epilepsy. Three patients
      had profound developmental delay; the other 11 patients had no or mild delay.
      INTERPRETATION: Children with neurocutaneous melanocytosis exhibit a wide range
      of intracranial and intraspinal abnormalities and variable clinical outcomes.

PMID- 22469365
TI  - Definitive setup of clinical scale procedure for ex vivo expansion of cord blood
      hematopoietic cells for transplantation.
AB  - We recently developed a clinical grade ex vivo cord blood expansion procedure
      enabling a massive amplification of hematopoietic progenitors without any loss of
      stem cell potential. This procedure, based on day 14 liquid cultures of cord
      blood CD34(+) cells, in medium Macopharma HP01 and in the presence of stem cell
      factor (SCF; 100 ng/ml), fms-related tyrosine kinase 3-ligand (Flt-3L; 100
      ng/ml), megakaryocyte growth and developmental factor (MGDF; 100 ng/ml), and
      granulocyte colony-stimulating factor (G-CSF; 10 ng/ml) had to be modified due to
      the commercially unavailability of clinical grade MGDF molecule. So MGDF was
      replaced by thrombopoietin (TPO) in fivefold lower dose (20 ng/ml), and culture
      time was reduced to 12 days. That way, a mean expansion fold of 400, 80, and 150
      was obtained for total cells, CD34(+) cells, and colony-forming cells (CFCs),
      respectively. This amplification was associated with a slight enhancing effect on
      stem cells [Scid repopulating cells (SRCs)]. These are the ultimate preclinical
      modifications of a clinical grade expansion protocol, which is already employed
      in an ongoing clinical trial.

PMID- 22469366
TI  - Radiology's golden opportunity.

PMID- 22469367
TI  - One hundred days of solitude.

PMID- 22469368
TI  - Ethics and the limits of principles.

PMID- 22469370
TI  - New producers of medical imaging equipment.

PMID- 22469371
TI  - Choosing greatness in leadership.

PMID- 22469372
TI  - Radiologists as valued consultants: IT can help.

PMID- 22469373
TI  - ACR Appropriateness Criteria(r) external-beam radiation therapy treatment
      planning for clinically localized prostate cancer.
AB  - Image-based radiation treatment planning and localization have contributed to
      better targeting of the prostate and sparing of normal tissues. Guidelines are
      needed to address radiation dose delivery, including patient setup and
      immobilization, target volume definition, treatment planning, treatment delivery
      methods, and target localization. Guidelines for external-beam radiation
      treatment planning have been updated and are presented here. The use of
      appropriate doses, simulation techniques, and verification of field setup are
      essential for the accurate delivery of radiation therapy. 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- 22469374
TI  - Exposure to ionizing radiation and estimate of secondary cancers in the era of
      high-speed CT scanning: projections from the Medicare population.
AB  - PURPOSE: The aims of this study were to analyze the distribution and amount of
      ionizing radiation delivered by CT scans in the modern era of high-speed CT and
      to estimate cancer risk in the elderly, the patient group most frequently imaged
      using CT scanning. METHODS: A retrospective cohort study was conducted using
      Medicare claims spanning 8 years (1998-2005) to assess CT use. The data were
      analyzed in two 4-year cohorts, 1998 to 2001 (n = 5,267,230) and 2002 to 2005 (n
      = 5,555,345). The number and types of CT scans each patient received over the 4
      year periods were analyzed to determine the percentage of patients exposed to
      threshold radiation of 50 to 100 mSv (defined as low) and >100 mSv (defined as
      high). The National Research Council's Biological Effects of Ionizing Radiation
      VII models were used to estimate the number of radiation-induced cancers.
      RESULTS: CT scans of the head were the most common examinations in both Medicare
      cohorts, but abdominal imaging delivered the greatest proportion (43% in the
      first cohort and 40% in the second cohort) of radiation. In the 1998 to 2001
      cohort, 42% of Medicare patients underwent CT scans, with 2.2% and 0.5% receiving
      radiation doses in the low and high ranges, respectively. In the 2002 to 2005
      cohort, 50% of Medicare patients received CT scans, with 4.2% and 1.2% receiving
      doses in the low and high ranges. In the two populations, 1,659 (0.03%) and 2,185
      (0.04%) cancers related to ionizing radiation were estimated, respectively.
      CONCLUSIONS: Although radiation doses have been increasing along with the
      increasing reliance on CT scans for diagnosis and therapy, using conservative
      estimates with worst-case scenario methodology, the authors found that the risk
      for secondary cancers is low in older adults, the group subjected to the most
      frequent CT scanning. Trends showing increasing use, however, underscore the
      importance of monitoring CT utilization and its consequences.

PMID- 22469375
TI  - A medical student perspective on self-referral and overutilization in radiology:
      application of the four core principles of medical ethics.
AB  - There is contention within the medical community surrounding imaging self
      referral, in which providers refer patients to imaging facilities from which they
      receive financial returns. Controversy surrounds the assertion that self-referral
      leads to overutilization, or the application of imaging resources and services in
      situations in which patients are unlikely to benefit. Proponents of self-referral
      claim that the practice provides increased convenience, timelier diagnosis, more
      expeditious treatment, and decreased cost, while opponents believe that the
      practice results in the inappropriate ordering of unnecessary imaging studies.
      Given the importance of this subject and the magnitude of its potential economic
      impact, it is important to restore objectivity. The 4 core principles of medical
      ethics--autonomy, nonmaleficence, beneficence, and justice--represent a useful
      and well-established paradigm. This review article addresses the question of
      whether self-referral upholds these 4 principles and thus whether it is an
      ethical practice.

PMID- 22469376
TI  - Access to radiologic reports via a patient portal: clinical simulations to
      investigate patient preferences.
AB  - PURPOSE: The aim of this study was to determine (1) the patient-preferred timing
      characteristics of a system for online patient access to radiologic reports and
      (2) patient resource needs and preferences after exposure to reports. METHODS:
      Adult outpatients from a single imaging center completed researcher-administered
      electronic questionnaires. Participants were exposed to 3 simulated clinical
      scenarios and asked to answer questions on the basis of what they thought they
      would do in each. Scenarios included symptomatology and written radiology reports
      that were nearly normal, seriously abnormal, and indeterminate, with reports
      containing typical medical terminology. Participants were asked about preferred
      timing for online access to reports, communication methods, educational
      resources, and alternative formats. McNemar's test correlated proportions and
      generalized estimating equations were used to evaluate responses. RESULTS:
      Participants (n = 53) most often preferred immediate access to reports: 32
      (60.2%) for the nearly normal scenario, 25 (47.2%) for the seriously abnormal
      scenario, and 24 (45.3%) for the indeterminate scenario. Three-day delayed access
      was next most commonly preferred: 15 (28.3%), 19 (35.8%), and 19 (35.8%),
      respectively. Forty-two participants (79.2%) preferred the portal method of
      notification over ways they have historically gotten results, with an increased
      proportion being satisfied with it overall (P < .04). Most would use a variety of
      educational resources and found alternative lay language conclusions and
      hyperlinks helpful. CONCLUSIONS: Some outpatients want immediate online access to
      complete, written radiologic reports and would use multiple resources to
      understand report contents. Effects of immediate access on provider workflow and
      on anxiety and autonomy among a diverse population of patients still need to be
      studied.

PMID- 22469377
TI  - Application of the RADPEERTM scoring language to interpretation discrepancies
      between diagnostic radiology residents and faculty radiologists.
AB  - PURPOSE: The objectives of this study were to assess the rate of discrepancies
      between radiology residents and faculty radiologists at an academic hospital
      using the RADPEER(TM) scoring language and to determine if a correlation existed
      between assigned RADPEER score (2, 3, or 4) and the clinical significance of the
      error. METHODS: Over 19 months, preliminary resident interpretations were graded
      using the RADPEER scoring system. A retrospective review of discrepant cases was
      performed to assess the percentage of discrepancy, change in clinical management,
      and identification of error patterns. RESULTS: Of 2,255 preliminary
      interpretations, 29 discrepancies (1.29%) were judged to be potentially
      clinically significant. Of these, 14 (0.62%) resulted in immediate changes in
      clinical management. Discrepancies assigned RADPEER scores of 3 or 4 were
      significantly more likely to be judged clinically significant than those assigned
      scores of 2 (54.5% of 33 studies graded 3 or 4 and 7.7% of 142 studies graded 2,
      P < .0001). CT imaging generated a higher percentage of discrepancies that were
      predicted to be clinically significant than plain-film radiography, as well as a
      higher percentage of discrepancies that resulted in immediate changes in
      management, but the incidence of each remained low overall (<=2.1%). CONCLUSIONS:
      Discrepancy rates in this study are comparable with previously reported data for
      discrepancies between attending radiologists and those between attending
      radiologists and residents data. A significant correlation was observed between
      increasing RADPEER scores and the clinical significance of discrepancies. This
      study supports the use of the RADPEER scoring language as both a resident quality
      assurance measure and an educational tool for quality improvement.

PMID- 22469378
TI  - Comparative analysis of physician extender curricular requirements in radiology:
      a detailed view.
AB  - PURPOSE: This article provides a detailed analysis comparing the educational
      requirements for physician assistants, nurse practitioners, and radiologist
      assistants (RAs) working in radiology. The authors examine the curricular
      requirements as they pertain to radiology for each program and highlight the
      advantages and limitations of each within potential roles in radiology. METHODS:
      A literature review was performed using the following databases: CINAHL Plus,
      MEDLINE, and Academic Search Complete. The search parameters were English
      language peer-reviewed articles published from 2002 through 2010. The search
      terms included "physician assistant," "nurse practitioner," "radiologist
      assistant," "radiology practitioner assistant," and "physician extender." The
      inclusion term applied was "radiology" to further hone results. RESULTS: The RA
      curriculum includes a core education that is comparable with the physician
      assistant and nurse practitioner curricula, with the exception of prescriptive
      authority and health promotion and disease prevention. The RA curriculum adds
      instruction in radiobiology, radiation safety, radiologic procedures,
      fluoroscopic unit operation and safety, and radiopharmaceuticals. CONCLUSIONS:
      The RA curriculum is specific for the radiologic imaging area and advantageous to
      radiologists, radiology managers, and patients undergoing diagnostic procedures.

PMID- 22469379
TI  - Administrative organization in diagnostic radiology residency program leadership.
AB  - PURPOSE: The aim of this study was to document the current state of
      administrative structure in US diagnostic radiology (DR) residency program
      leadership. A secondary objective was to assess for correlation(s), if any, with
      DR residency programs that equipped positions such as assistant, associate, and
      emeritus program director (PD) with respect to residency size and region of the
      country. METHODS: The Fellowship and Residency Electronic Interactive Database,
      as well as direct communication and programmatic Web site searches, were used to
      gather data regarding current US DR residency leadership. Data collected included
      the presence of additional leadership titles, including assistant PD, associate
      PD, and PD emeritus, and how many faculty members currently held each position.
      Programs were excluded if results could not be identified. Analysis of variance
      and t tests were used to estimate the correlations of the size of a residency
      with having additional or shared PD positions and the types of positions,
      respectively. Chi-square tests were used to assess for any regional differences.
      RESULTS: As of the time of this project, the Fellowship and Residency Electronic
      Interactive Database defined 186 US DR residency programs. A total of 173
      programs (93%) were included in the analysis; the remainder were excluded because
      of unavailability of relevant data. Seventy-two percent (124 of 173) of programs
      had additional DR leadership positions. Of these, 30 programs (17%) had more than
      one such position. There were no significant differences in the sizes of the
      programs that used these additional positions (mean, 25 +/- 12; range, 6-72)
      compared with those that did not (mean, 24 +/- 12; range, 7-51). There were no
      significant differences between programs that had additional positions with
      respect to region of the country. CONCLUSIONS: The majority of US DR residency
      programs used some form of additional DR leadership position. In the majority of
      cases, this was in the form of an assistant or associate PD. Nearly one-fifth of
      programs studied had more than one such position. This is a positive model for
      the depth and breadth of management of US residency programs, serving both as a
      template for matrixed leadership and as a source of leadership succession
      planning.

PMID- 22469380
TI  - To disclose or not to disclose, that is the question: issues to consider before
      responding to a subpoena.

PMID- 22469381
TI  - Five roles for quality leadership in radiology.

PMID- 22469382
TI  - Overcoming the learning curve in supine pediatric proton craniospinal
      irradiation.

PMID- 22469383
TI  - Progress in improving radiology residency training in Finland.

PMID- 22469384
TI  - The University of Colorado Radiology Adult Dose-Risk Smartcard.

PMID- 22469385
TI  - Chief residency in radiology: a primer for success.

PMID- 22469388
TI  - Ionizing radiation in abdominal CT and the ACR Appropriateness Criteria(r).

PMID- 22469389
TI  - Detection of Plasmodium spp. in human feces.
AB  - Comparison of diagnostic methods for Plasmodium spp. in humans from Uganda and
      the Central African Republic showed that parasites can be efficiently detected by
      PCR in fecal samples. These results, which rely solely on PCR-based examination
      of feces, validate numerous estimates of the prevalence of malaria in great apes.

PMID- 22469390
TI  - Laser irradiation did not increase the proliferation or the differentiation of
      stem cells from normal and inflamed dental pulp.
AB  - OBJECTIVE: Low-level laser therapy (LLLT) has been reported to be responsible for
      promoting photostimulatory and photobiomodulatory effects in vivo and in vitro,
      stimulating cell growth, increasing cell metabolism, improving cell regeneration
      and invoking an anti-inflammatory response. This study was performed in order to
      investigate whether low-level laser therapy could increase the proliferation and
      differentiation potentials of hDPSC isolated from healthy dental pulps and from
      inflamed pulps. DESIGN: Human dental pulp stem cells (hDPSC) were isolated from
      normal and inflamed dental pulps from different patients. STRO-1-positive cells
      were isolated and irradiated with a red low-level laser (660 nm) in four
      different energy fluences (0.05, 0.30, 7 and 42 J/cm(2)); the authors
      hypothesized that the first three fluences would promote biostimulatory effects,
      whereas the highest dose would induce antiproliferative effects. The two lower
      fluences were produced by irradiating the two higher fluences through a dentine
      disc, which was used to simulate a clinical condition. The proliferation and the
      cell odonto-osteogenic differentiation competence were compared. RESULTS: No
      statistically significant differences were observed between the proliferation
      rates and the relative productions of mineralized nodules compared to the
      respective controls, either for hDPSC from normal or inflamed dental pulps.
      CONCLUSIONS: The irradiation with low-level InGaAlP red low-level laser (660 nm)
      in four different energy fluences (0.05, 0.30, 7 and 42 J/cm(2)) potentiated
      neither proliferation nor odonto-osteogenic differentiation of hDPSC isolated
      from patients with normal and inflamed pulps.

PMID- 22469391
TI  - Absence or weak correlation between chewing side preference and lateralities in
      primary, mixed and permanent dentition.
AB  - OBJECTIVES: To determine whether chewing side preference (CSP) is correlated to
      lateralities (handedness, footedness, eyedness and earedness) in primary, mixed
      and permanent dentitions. DESIGN: Three-hundred subjects were divided into 3
      groups: Group 1--100 children 3-5 years old, primary dentition; Group 2--100
      children 6-12 years old, mixed dentition; Group 3--100 subjects 18-47 years old,
      permanent dentition. CSP was determined using a method developed by Mc Donnell et
      al. Subjects were given a piece of gum and the position of the chewing gum was
      recorded 7 times as right or left. Subjects were classified as 'observed
      preferred chewing side' (OPCS) when they performed 5/7, 6/7 or 7/7 strokes on the
      same side. OPCS corresponded to the CSP. Laterality tests were performed for
      handedness, footedness, eyedness and earedness tasks. The Chi-square (chi(2)) and
      phi correlation (r) tests were used to investigate significant correlations
      between CSP and sidedness. RESULTS: There was a significant correlation between
      chewing and earedness (p=0.00), although there was weak positive correlation
      (r=0.30) for primary dentition. There were significant correlations between
      chewing and handedness (p=0.02; r=0.25) and chewing and footedness (p=0.02;
      r=0.26), however, there were weak positive correlations for mixed dentition;
      there were significant correlations between chewing and handedness (p=0.02;
      r=0.26); chewing and footedness (p=0.00; r=0.33) and chewing and earedness
      (p=0.01; r=0.29); however, there were weak positive correlations for permanent
      dentition. CONCLUSION: It may be concluded that CSP can be significantly
      correlated with: earedness for primary dentition; handedness and footedness for
      mixed dentition; handedness, footedness and earedness for permanent dentition,
      but these are weak positive relationships. Future work on larger samples of left-
      and right-sided individuals is required to validate the findings.

PMID- 22469392
TI  - Feasibility and preliminary clinical outcomes of robotic laparoendoscopic single
      site (R-LESS) pyeloplasty using a new single-port platform.
AB  - This study tested the technical feasibility and short-term perioperative outcomes
      of the novel da Vinci Single-Site Instrumentation platform for the treatment of
      upper ureteropelvic junction obstruction (UPJO) in a selected group of patients.
      Nine patients underwent robotic laparoendoscopic single-site (R-LESS) pyeloplasty
      using a new single-site platform for UPJO at our department of urology. All the
      procedures were completed without the need for traditional robotic surgery or
      laparoscopic/open conversion, although in one patient with congenital
      hepatomegaly it was necessary to use an auxiliary 3-mm trocar to retract the
      liver properly and expose the surgical field. Mean operative time was 166 min,
      and no intraoperative complications were recorded. The indwelling catheter was
      removed on postoperative day 2 in five patients and on postoperative day 3 in
      four patients. Patients were discharged the day after drain removal. One patient
      experienced transient hyperpyrexia, treated with antibiotics. No other
      complications were observed. All patients had the DJ stent removed 4 wk after
      surgery, following a negative urine culture and abdominal ultrasound evaluation.
      The five patients who reached a 3-mo follow-up had a clinical resolution of
      preoperative symptoms and hydronephrosis at the abdominal ultrasound. The same
      results were maintained in the two patients with 6-mo follow-up evaluations. In
      selected patients, R-LESS pyeloplasty using the new single-port platform appears
      to be a technically feasible and reproducible surgical procedure for the
      minimally invasive treatment of UPJO. Prolonged follow-up and larger series are
      required to confirm its potential role as a valid alternative to standard robotic
      pyeloplasty.

PMID- 22469393
TI  - Anatomic study of periprostatic nerve distribution: immunohistochemical
      differentiation of parasympathetic and sympathetic nerve fibres.
AB  - BACKGROUND: Many authors advocate a high anterior incision during nerve-sparing
      radical prostatectomy (RP) to improve potency results. Despite a growing number
      of studies describing autonomic nerves in the ventrolateral position of the
      prostate, little is known about their quality and their role in erectile
      function. OBJECTIVE: The intention of this study was a detailed characterisation
      of the topographic distribution of periprostatic nerves, including
      immunohistochemical differentiation of proerectile parasympathetic from
      sympathetic nerves. DESIGN, SETTING, AND PARTICIPANTS: A total of 228 whole-mount
      sections of 38 prostates (base, middle, apex) from patients following non-nerve
      sparing laparoscopic RP were analysed. Immunohistochemical analysis was performed
      using antibodies against tyrosine hydroxylase for sympathetic and vesicular
      acetylcholine transporter for parasympathetic nerve fibre staining. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Quantification of periprostatic
      parasympathetic and sympathetic nerves was performed after defining prostatic
      regions via a digital grid. Differences among three independent variables were
      tested with the nonparametric Kruskal-Wallis test. RESULTS AND LIMITATIONS: The
      total number of parasympathetic nerves did not decrease from the base to the
      apex. They were dispersed at the base and mainly located dorsolaterally at the
      apex, with 14.6% above the horizontal line at the base and only 1.5% at the apex.
      In contrast, the total number of sympathetic nerves decreased significantly from
      base to apex, with a constant proportion of ventrolateral nerves between 9%
      (base) and 6.2% (apex). This anatomic study is limited by the investigation of
      postprostatectomy specimens and the lack of functional results. CONCLUSIONS:
      Despite the presence of ventrolateral periprostatic nerves, only a minority of
      these nerves seems to have a parasympathetic proerectile quality. The arguments
      in favour of a high anterior incision during nerve-sparing prostatectomy might
      not only include preserved nerves but also other factors, such as reduced
      traction or improved anatomic support of the neural structures.

PMID- 22469395
TI  - Systematic review: Individuals' goals for surrogate decision-making.
AB  - OBJECTIVES: To determine to what extent current practice promotes the goals of
      individuals who did not designate a surrogate while competent with respect to
      decision-making during periods of decisional incapacity. DESIGN: Systematic
      literature search for studies published in English and listed in PubMed, Scopus,
      Embase, CINAHL, or PsycINFO. Studies were eligible if they provided quantitative
      or qualitative empirical data on how adults want treatment decisions to be made
      for them during periods of incapacity. SETTING: Primarily United States, with six
      other countries. PARTICIPANTS: Fourteen qualitative articles, representing 11
      distinct data sets, and 26 quantitative articles, representing 25 distinct data
      sets, providing data on the views of 22,828 individuals, met the inclusion
      criteria. Most of the respondents were elderly or seriously ill. MEASUREMENTS:
      Quantitative surveys and qualitative interview studies assessing individuals'
      goals. RESULTS: The majority wanted close family members to act as their
      surrogate. The most common reason for preferring family members was the belief
      that they know which treatments the patient would want. Individuals also wanted
      to reduce the burden on their families. There was significant variation in the
      extent to which respondents wanted their surrogates to have leeway when making
      treatment decisions. CONCLUSION: Individuals have three primary goals with
      respect to making treatment decisions for them during periods of incapacity:
      involve their family, treat them consistently with their own treatment
      preferences, and reduce the burden on their family. Unfortunately, prior
      systematic reviews have found that family members often are not able to determine
      which treatment patients want, and family members frequently experience
      substantial distress when acting as surrogates. These findings suggest that
      current practice frequently fails to promote individuals' primary goals for
      treatment decision-making. Future research should evaluate ways to better promote
      individuals' goals. In the meantime, clinicians should be aware of these findings
      and should encourage patients to document their own goals, including their
      treatment preferences and their preferences regarding how they want decisions to
      be made for them during periods of decisional incapacity.

PMID- 22469394
TI  - Leishmania resistance to miltefosine associated with genetic marker.

PMID- 22469396
TI  - Technical update on magnetic resonance imaging of the shoulder.
AB  - Improvement in both hardware and software has opened up new opportunities in
      magnetic resonance (MR) imaging of the shoulder. MR imaging at 3-T has become a
      reality, with the prospect of 7-T imaging on the horizon. The art of MR
      arthrography continues to improve, aided by the use of novel imaging positions.
      New techniques for three-dimensional imaging, the reduction of metal artifact,
      and biochemical imaging of cartilage hold great promise.

PMID- 22469397
TI  - Novel anatomic concepts in magnetic resonance imaging of the rotator cuff tendons
      and the footprint.
AB  - The anatomic and histologic descriptions of the rotator cuff tendons and
      footprints are continuously evolving, and new discoveries have led to novel
      concepts in our understanding of rotator cuff tendon pathology. These concepts
      may be translated into the analysis of these footprints with imaging methods,
      particularly magnetic resonance imaging.

PMID- 22469398
TI  - The rotator cable: magnetic resonance evaluation and clinical correlation.
AB  - The rotator cable is an extension of the coracohumeral ligament coursing along
      the undersurface of the supraspinatus and infraspinatus tendons. The rotator
      cable is thought to play a role in the biomechanical function of the intact and
      torn rotator cuff. It can be seen on all the imaging planes used for the
      conventional magnetic resonance imaging of the shoulder. Clinically, the
      integrity of the rotator cable can play a role in the treatment selection for
      patients with a rotator cuff tear.

PMID- 22469399
TI  - Magnetic resonance imaging of rotator cuff disease and external impingement.
AB  - Magnetic resonance (MR) imaging plays a major role in helping to identify rotator
      cuff disease and in demonstrating the pathology associated with external
      impingement. Many surgeons rely on MR imaging to assist in decision making and
      presurgical planning for patients with rotator cuff pain. This article reviews
      the etiology of external impingement and rotator cuff tears, and describes the MR
      imaging appearance of the normal and the pathologic rotator cuffs. It focuses on
      the supraspinatus tendon because this is the tendon involved in 95% of rotator
      cuff tears.

PMID- 22469400
TI  - Internal impingement syndromes.
AB  - Internal causes of impingement are secondary to rotator cuff and capsular
      dysfunction and are categorized by the location of the impingement and the
      underlying pathophysiological or mechanical cause of the impingement. These
      include posterosuperior impingement, anterosuperior impingement, anterior
      impingement, and entrapment of the long head of the biceps tendon. The objective
      of this article is to review magnetic resonance imaging findings of each of the 4
      types of internal impingement syndromes and discuss the pathophysiology behind
      the impingement.

PMID- 22469401
TI  - Anatomic variants and pitfalls of the labrum, glenoid cartilage, and glenohumeral
      ligaments.
AB  - Magnetic resonance (MR) imaging is the primary diagnostic imaging modality for
      the evaluation of patients with suspected internal derangement of the shoulder
      joint. Awareness and understanding of the complex anatomy of the shoulder
      articulation and the ability to recognize normal anatomic variants and potential
      imaging pitfalls are critical to accurate interpretation of conventional and
      arthrographic MR imaging studies. This review discusses the normal anatomy and
      anatomic variants of the glenoid labrum, articular cartilage, and glenohumeral
      ligaments. An improved understanding of normal anatomy, biomechanics, and
      variants will help to avoid potential pitfalls in the interpretation of
      noncontrast and arthrographic shoulder MR imaging examinations.

PMID- 22469402
TI  - The rotator interval and long head biceps tendon: anatomy, function, pathology,
      and magnetic resonance imaging.
AB  - The rotator interval is an anatomically defined triangular area located between
      the coracoid process, the superior aspect of the subscapularis, and the anterior
      aspect of the supraspinatus. It is widely accepted that the rotator interval
      structures fulfill a role in biomechanics and pathology of the glenohumeral joint
      and long head biceps tendon. However, there is ongoing debate regarding the
      biomechanical details and the indications for treatment. A better understanding
      of rotator interval anatomy and function will lead to improved treatment of
      rotator interval abnormalities, and guide the indications for imaging and
      surgical intervention.

PMID- 22469403
TI  - The throwing shoulder: the orthopedist perspective.
AB  - The extreme range of motion at the shoulder, high velocities and stresses, and
      repetitive nature of the throwing motion place the throwing athlete at risk for a
      wide range of pathologic entities. The treating orthopedist must fully understand
      the biomechanics of the throwing cycle and how it contributes to the potential
      injuries in the throwing shoulder during each phase of the throwing motion. The
      goal of orthopedic care and rehabilitation is to allow the throwing athlete to
      return symptom free to the preinjury level of competition.

PMID- 22469404
TI  - Superior labrum anterior and posterior lesions and microinstability.
AB  - The glenohumeral joint provides the greatest range of motion of any joint in the
      human body. Over the past several decades, histologic studies, biomechanical
      studies, and improved arthroscopic techniques have contributed to improved
      knowledge and treatment of glenohumeral joint abnormalities. Continuing advances
      in magnetic resonance technology have allowed for improved noninvasive
      visualization of the stabilizers of the shoulder. This article reviews the
      concept of glenohumeral joint microinstability and its relationship with superior
      labrum anterior and posterior (SLAP) lesions, reviews the role of the labrum as a
      stabilizer of the shoulder, and focuses on the diagnosis and classification of
      SLAP lesions.

PMID- 22469405
TI  - Magnetic resonance imaging in glenohumeral instability.
AB  - The glenohumeral joint enables tremendous range of motion at the expense of
      stability. Functional stability is maintained by the synchronous coordination of
      complex static and dynamic structures. Symptomatic glenohumeral instability most
      often results from injury to the inferior labral-ligamentous complex, the primary
      passive stabilizer of the shoulder. This article reviews the structures important
      in glenohumeral stabilization and illustrates their normal appearances and the
      abnormalities associated with anterior, posterior, and multidirectional
      instability. These lesions are discussed in the context of therapeutic decision
      making.

PMID- 22469406
TI  - Postoperative shoulder magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) and MR arthrography have proven invaluable for
      managing the postoperative shoulder, particularly in relation to the rotator cuff
      and labrum. MRI has proven to be an accurate imaging technique for
      differentiating expected findings versus complications in the postoperative
      setting. The transition from metallic hardware to bioabsorbable suture anchors
      used in orthopedic surgery has rendered less metallic susceptibility artifact
      over the years, allowing more accurate interpretation of MR images. This article
      gives a pictorial review of various expected postoperative findings in the
      shoulder and complications related to repair of the rotator cuff and labrum.

PMID- 22469407
TI  - Magnetic resonance imaging of the pediatric shoulder.
AB  - Magnetic resonance (MR) imaging is a modality widely used to assess shoulder
      abnormalities in children. A thorough understanding of the development of the
      shoulder and adequate MR techniques are crucial in the radiologic evaluation. The
      immature skeleton is particularly vulnerable to insults such as trauma,
      infection, and inflammation, and responds in unique ways. The pediatric shoulder
      can also be affected by complex congenital deformities such as brachial plexus
      injuries. In addition, certain neoplasms can be seen specifically in the young
      patient. MR imaging plays a critical role in the initial diagnostic evaluation
      and in assessing posttreatment responses.

PMID- 22469408
TI  - Magnetic resonance imaging of shoulder arthropathies.
AB  - The role of magnetic resonance imaging in evaluating shoulder arthropathies is
      evolving. This article reviews 4 of the major arthropathies: septic arthritis,
      rheumatoid arthritis, calcium pyrophosphate dihydrate (CPPD) deposition disease,
      and hydroxyapatite disease (HAD), with special attention to their magnetic
      resonance imaging features. Comfort with identifying these entities allows
      appropriate and prompt treatment, which is critical for joint preservation in the
      case of infection, for maximal therapeutic efficacy of disease-modifying drugs in
      the case of rheumatoid arthritis, and for expediting symptomatic relief in the
      cases of CPPD deposition disease and HAD.

PMID- 22469409
TI  - Entrapment neuropathies of the shoulder.
AB  - Entrapment neuropathies are a rare but presumably underdiagnosed cause of
      shoulder pain and painful instability. Radiologists must be aware of the clinical
      presentations and imaging features of these neuropathies because they may be the
      first to suggest these diagnoses. In this article, instead of a classical nerve
      by-nerve approach, entrapment neuropathies are deciphered according to the
      clinical situation: which anatomic structures may be involved, how to explore
      them, which imaging abnormalities can be expected, how to manage differential
      diagnoses, and which therapeutic options can be considered.

PMID- 22469410
TI  - Update on the shoulder. Preface.

PMID- 22469412
TI  - Words of wisdom. Re: Phase III study of molecularly targeted adjuvant therapy in
      locally advanced urothelial cancer of the bladder based on p53 status.

PMID- 22469413
TI  - Words of wisdom. Re: Germline mutations in HOXB13 and prostate-cancer risk.

PMID- 22469414
TI  - Words of wisdom. Re: International phase III trial assessing neoadjuvant
      cisplatin, methotrexate, and vinblastin chemotherapy for muscle-invasive bladder
      cancer: long-term results of the BA06 30894 trial.

PMID- 22469415
TI  - Words of wisdom. Re: Adjuvant radiotherapy following radical prostatectomy for
      prostate cancer.

PMID- 22469416
TI  - Words of wisdom. Re: Association of androgen deprivation therapy with
      cardiovascular death in patients with prostate cancer: a meta-analysis of
      randomized trials.

PMID- 22469417
TI  - Words of wisdom. Re: Efficacy of quadrivalent human papillomavirus vaccine
      against human papillomavirus infection and disease in males.

PMID- 22469418
TI  - Effects of natural S-equol supplements on overweight or obesity and metabolic
      syndrome in the Japanese, based on sex and equol status.
AB  - OBJECTIVES: Epidemiologic studies indicate that soy intake has an important role
      in the prevention of age-related health problems. Daidzein, the principal
      isoflavone contained in soy, is converted to S-equol by the intestinal bacteria.
      Not all individuals, however, can produce S-equol, which is considered the most
      biologically active metabolite. We studied the effects of a natural S-equol
      supplement on metabolic parameters associated with overweight or obesity and
      metabolic syndrome. METHODS: The study was a randomized, double-blinded, placebo
      controlled, crossover design with no washout period. All subjects were considered
      overweight or obese if they had a body mass index >= 25 kg/m(2) . Placebo or
      natural S-equol tablets containing 10 mg S-equol were orally ingested each day
      for 12 weeks. A total of 54 Japanese overweight or obese outpatients were
      enrolled. The equol phenotype was determined, and various metabolic parameters,
      including cardio-ankle vascular index (CAVI), were measured. RESULTS: Equol non
      producers comprised 67.9% of the overweight or obese subjects. The ratio of equol
      non-producers in this overweight or obese subject group was higher than the
      previously reported ratio of equol non-producers (approximately 50%) in the
      general population. Compared with the placebo group, intervention with natural S
      equol led to a significant decrease in HbA1c, serum low-density lipoprotein
      cholesterol (LDL-C) levels and CAVI score. Furthermore, the effect was more
      prominent in the subgroup of female equol non-producers. CONCLUSION: The ratio of
      equol non-producers in overweight or obese populations might be higher than
      generally reported. Natural S-equol might have a role in glycaemic control and in
      the prevention of cardiovascular disease by its effects to lower LDL-C levels and
      CAVI scores in overweight or obese individuals.

PMID- 22469420
TI  - MRSA model of learning and adaptation: a qualitative study among the general
      public.
AB  - BACKGROUND: More people in the US now die from Methicillin Resistant
      Staphylococcus aureus (MRSA) infections than from HIV/AIDS. Often acquired in
      healthcare facilities or during healthcare procedures, the extremely high
      incidence of MRSA infections and the dangerously low levels of literacy regarding
      antibiotic resistance in the general public are on a collision course.
      Traditional medical approaches to infection control and the conventional attitude
      healthcare practitioners adopt toward public education are no longer adequate to
      avoid this collision. This study helps us understand how people acquire and
      process new information and then adapt behaviours based on learning. METHODS:
      Using constructivist theory, semi-structured face-to-face and phone interviews
      were conducted to gather pertinent data. This allowed participants to tell their
      stories so their experiences could deepen our understanding of this crucial
      health issue. Interview transcripts were analysed using grounded theory and
      sensitizing concepts. RESULTS: Our findings were classified into two main
      categories, each of which in turn included three subthemes. First, in the
      category of Learning, we identified how individuals used their Experiences with
      MRSA, to answer the questions: What was learned? and, How did learning occur? The
      second category, Adaptation gave us insights into Self-reliance, Reliance on
      others, and Reflections on the MRSA journey. CONCLUSIONS: This study underscores
      the critical importance of educational programs for patients, and improved
      continuing education for healthcare providers. Five specific results of this
      study can reduce the vacuum that currently exists between the knowledge and
      information available to healthcare professionals, and how that information is
      conveyed to the public. These points include: 1) a common model of MRSA learning
      and adaptation; 2) the self-directed nature of adult learning; 3) the focus on
      general MRSA information, care and prevention, and antibiotic resistance; 4) the
      interconnected nature of adaptation; and, 5) the need for a consistent step by
      step plan to deal with MRSA provided at the time of diagnosis.

PMID- 22469421
TI  - How twins differ: multiple pregnancy and the use of health care in the 2008
      Nigeria Demographic and Health Survey.
AB  - OBJECTIVES: To (i) document the incidence of multiplicity in Nigeria, (ii)
      compare healthcare utilization during pregnancy and at delivery for singleton and
      multiple pregnancies (iii)and investigate whether antenatal care modifies the
      relationship between multiplicity and likelihood of having skilled attendance.
      METHODS: This observational study was a secondary analysis of the 2008 Nigeria
      Demographic and Health Survey and included 17,635 women who gave birth to a live
      infant between 2003 and 2008. Multivariate logistic regression with adjustment
      for weighting, clustering and confounding was used to investigate associations
      and look for effect modification. RESULTS: There were 18.5 multiple pregnancies
      per 1000 maternities. Multiple births had nearly six times the chance of neonatal
      mortality (AOR 5.74). Mothers with multiple births had more skilled attendance
      (AOR 1.75), but similar antenatal care utilization (AOR 0.95) as women with a
      singleton pregnancy. Women with multiple pregnancies attending antenatal care had
      more visits (mean 9.0 vs. 8.2), blood pressure checks (OR 1.52) and urine tests
      (OR 1.51). Although antenatal care was strongly associated with skilled
      attendance, there was no evidence that this was more so for twins than
      singletons. CONCLUSIONS: Multiplicity in Nigeria is not just a common occurrence,
      but an indicator of a high-risk pregnancy. The fact that the use of antenatal
      care by women with a multiple pregnancy is not associated with a
      disproportionately greater use of skilled delivery care raises questions about
      the quality of antenatal services. Services should encourage and link all women
      and especially high-risk women to skilled attendance at delivery.

PMID- 22469422
TI  - Pulmonary vein isolation for the treatment of drug-refractory atrial fibrillation
      in adults with congenital heart disease.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in adults with
      congenital heart disease (CHD). Long-term antiarrhythmic therapy (AAT) in these
      patients has significant shortcomings. The safety and efficacy of pulmonary vein
      antrum isolation (PVAI) for the treatment of AF in CHD is presently unknown.
      HYPOTHESIS: We hypothesized that PVAI for AF in patients with CHD is effective
      and safe. METHODS: We reviewed a prospective cohort of 4315 patients (age >= 18)
      undergoing PVAI for drug refractory AF at a single institution and identified 36
      consecutive patients with CHD (single ventricle physiology, tetralogy of Fallot,
      coarctation of the aorta, ventricular septal defects, atrial septal defects (ASD)
      and cardiomyopathy resulting from anomalous origin of the left main coronary from
      the pulmonary artery). A second cohort of 355 consecutive patients with
      noncongenital structural heart disease (NSHD) (coronary artery disease, valvular
      heart disease, ejection fraction <50%, or prior noncongenital cardiac surgery)
      undergoing PVAI during the same time period was used as a control. Success was
      defined as freedom from AF starting two months after PVAI in the absence AAT
      until the end of follow-up. Partial success was defined as freedom from AF in the
      presence of AAT until the end of follow-up. Combined success was defined as the
      sum of success and partial success. We compared the outcomes with the use of
      propensity-score matching in the overall cohort. RESULTS: Patients with NSHD were
      older and had higher prevalence of hypertension (P < .01), diabetes (P < .01) and
      hyperlipidemia (P < .01). The most common CHD lesion was ASD (61%) and the most
      common NSHD lesion was valvular heart disease (57%). After one PVAI, success was
      achieved in 42% and 53% at 300 days in the CHD and NSHD groups respectively. Four
      year success was achieved in 27% and 36% in the CHD and NSHD groups,
      respectively. There were no significant differences in the success rates between
      patients groups (P= .46), nor were there any differences in left atrial size or
      changes in ejection fraction after one or two PVAI in the respective groups.
      Complication rates between the CHD and NSHD groups were similar (15% vs. 11%, P=
      .42) except for a higher risk of vascular site complications in patients with CHD
      (8% vs. 1%, P < .05). CONCLUSION: PVAI is an attractive treatment modality in
      drug refractory AF in CHD, with combined success rates in excess of 60%. The
      maintenance of sinus rhythm after PVAI in CHD appears similar to that of NSHD and
      warrants prospective validation.

PMID- 22469423
TI  - The effect of practice on the recall of salient information in obsessive
      compulsive disorder.
AB  - Deficits in memory and cognitive inhibition have been proposed as underlying
      mechanisms of obsessive-compulsive disorder (OCD). To test this hypothesis, an
      emotional variant of the retrieval-induced forgetting (RIF) paradigm was
      constructed which investigates whether repeated retrieval of previously learned
      material (Rp+) leads to enhanced forgetting of related but nonretrieved material
      (Rp-) in comparison to unrelated material (NRp). Paradigm (involving OCD
      relevant, neutral and negative material) was presented to 21 participants with
      OCD and 22 healthy controls. To compare personally relevant stimuli across
      groups, salience ratings of the material were included. RIF was not reduced in
      OCD per se. Tentative evidence was found for a weakened RIF effect for personally
      salient OCD-relevant material in OCD patients in comparison to healthy controls.

PMID- 22469424
TI  - Mental health problems among search and rescue workers deployed in the Haiti
      earthquake 2010: a pre-post comparison.
AB  - Search and rescue workers play an important role in rescuing trapped disaster
      victims. However, it is unclear whether they are at risk for post-disaster mental
      health problems. For this purpose we prospectively examined pre- and post
      deployment health among Dutch search and rescue workers (USAR NL) deployed in the
      devastating Haiti earthquake disaster (2010). The evening before departure (T1,
      response=100%) and 3 months post-deployment (T2, response=91%), Search and rescue
      workers were administered standardized questionnaires assessing health (SCL-90-R,
      RAND-36), including use of substances and mental health services utilization
      (N=51). At T2 event-related PTSD-symptoms (IES) and coping self-efficacy (CSE),
      and experiences during and after deployment were examined. At both surveys health
      problems were almost absent and no significant increases in health problems and
      use of substances were found. PTSD-symptomatology was very low and coping self
      efficacy rather high. Protective factors such as good team functioning,
      recognition and job satisfaction were clearly present, while risk factors such as
      sustained injuries or death of a co-worker were absent. Findings suggest that
      post-disaster health problems may (partly) be prevented by enhancing or restoring
      protective factors.

PMID- 22469425
TI  - Human parvovirus 4 infection, Cameroon.
AB  - In a post hoc analysis of samples collected in 2009, we determined seroprevalence
      of parvovirus 4 (PARV4) among elderly Cameroonians. PARV4 seropositivity was
      associated with receipt of intravenous antimalarial drugs, intramuscular
      streptomycin, or an intramuscular contraceptive, but not hepatitis C virus
      seropositivity. Findings suggest parenteral acquisition of some PARV4 infections.

PMID- 22469426
TI  - Can Simpson's paradox explain co-operation in Pseudomonas aeruginosa biofilms?
AB  - Co-operative behaviours, such as the production of public goods, are commonly
      displayed by bacteria in biofilms and can enhance their ability to survive in
      environmental or clinical settings. Non-co-operative cheats commonly arise and
      should, theoretically, disrupt co-operative behaviour. Its stability therefore
      requires explanation, but no mechanisms to suppress cheating within biofilms have
      yet been demonstrated experimentally. Theoretically, repeated aggregation into
      groups, interleaved with dispersal and remixing, can increase co-operation via a
      'Simpson's paradox'. That is, an increase in the global proportion of co
      operators despite a decrease in within-group proportions, via differential growth
      of groups. We investigate the hypothesis that microcolony formation and dispersal
      produces a Simpson's paradox that explains bacterial co-operation in biofilms.
      Using the production of siderophores in Pseudomonas aeruginosa as our model
      system for co-operation, we use well-documented co-operator and siderophore
      deficient cheat strains to measure the frequency of co-operating and cheating
      individuals, in-situ within-microcolony structures. We detected significant
      within-type negative density-dependant effects that vary over microcolony
      development. However, we find no evidence of Simpson's paradox. Instead, we see
      clear within-microcolony spatial structure (cheats occupying the interior
      portions of microcolonies) that may violate the assumption required for Simpson's
      paradox that group members share equally in the public good.

PMID- 22469427
TI  - L-index as a novel index to evaluate both the intensity and duration of
      lymphopenia after allogeneic hematopoietic stem cell transplantation.
AB  - We retrospectively investigated L-index, which evaluates both the intensity and
      duration of lymphopenia after allogeneic hematopoietic stem cell transplantation
      (HSCT) (n = 50). L-index was defined as the area over the lymphocyte curve during
      lymphopenia (absolute lymphocyte count < 700/MUL). We calculated the L-index from
      the start of conditioning to day 30 - L-index(30) - and to day 100 - L-index(100)
      - after HSCT. Multivariate analysis revealed that human leukocyte antigen
      mismatched donor, female gender, and non-lymphoid disease were significantly
      associated with high L-index(30). Grade III-IV acute graft-versus-host disease,
      alemtuzumab-containing regimen, and non-lymphoid disease were identified as
      independent significant factors for high L-index(100). Cytomegalovirus (CMV)
      antigenemia was detected > 3 cells/2 slides by C10/11 method in 30 patients (CMV
      AG >= 3 group) and was not detected in 20 patients (CMV-AG < 3 group). Although
      no significant difference was seen in absolute lymphocyte count on day 30 between
      the 2 groups, the L-index(30) was significantly higher in the CMV-AG >= 3 group
      than in the CMV-AG < 3 group (P = 0.050). L-index(30) was identified as an
      independent factor on CMV reactivation in multivariate analysis, when it was
      treated as a dichotomous variable with a cut-off value of 22,318, determined by
      receiver operating characteristic curve analysis. In conclusion, both the
      intensity and duration of lymphopenia in early phase after HSCT evaluated on the
      basis of L-index(30) showed significant association with CMV reactivation.

PMID- 22469428
TI  - Stimulation-history effects on the M100 revealed by its differential dependence
      on the stimulus onset interval.
AB  - The amplitudes of the most prominent component of auditory evoked magnetic fields
      and electrical potentials, the M100 and N100, recorded from the human scalp
      depend on the duration of the stimulus onset interval (SOI). Here, we show, using
      magnetoencephalography, that the SOI dependence of the M100 amplitude strongly
      depends upon whether stimuli with different SOIs are presented in a conventional
      block design or in a random manner. This differential dependence reveals that the
      M100 is affected not only by the stimulus evoking it and by its predecessor, but
      by a longer-term history of stimulation. We provide a parsimonious model that
      accounts for our findings with both designs in a quantitative manner. It assumes
      a transient, temporally asymmetric reduction in the excitability of a fraction of
      potentially excitable neurons. A rather stereotyped response function may
      therefore underlie the stimulation-history effects in the human auditory cortex.

PMID- 22469429
TI  - The canalicular system and the osteoblast domain in human secondary osteons.
AB  - The lacunar-canalicular system in human secondary osteons was examined by two
      complementary techniques: light microscopy analysis of undecalcified thick
      sections and the SEM cortex-fractured surface technique. Unlike the earlier
      definitions of 'osteoblastic domain' presented as the matrix volume produced by
      osteoblasts in the process of osteon infilling, this study measured the domain by
      the length of osteoblast dendritic processes. The domain extension was defined
      along radial vectors advancing from the reversal line towards the central canal.
      According to their lengths, domains were divided into three classes: peripheral,
      intermediate and internal. The mean length of peripheral domains was
      significantly shorter than those of the intermediate and internal domains. This
      suggests that the infilling process is modulated by an initial preparatory phase
      characterised by osteoblast adhesion to the wall of the cutting cone, and a
      limited matrix synthesis, followed by a regular matrix volume apposition
      organised in concentric layers. In addition to the radial canaliculae arranged
      along converging vectors in planes perpendicular to the central canal, we
      distinguished a further class of canaliculae, the equatorial canaliculae
      originating from the major perimeter of the lacuna and spreading out radially in
      the plane of the same lacuna (therefore, perpendicularly to the radial
      canaliculae). The whole lacunar-canalicular network was structured as a closed
      system around the vascular axis of the central canal with very few canaliculae
      crossing the reversal line and connecting the neighbouring osteons. These
      anatomical observations contribute to our knowledge of lacunar-canalicular system
      development.

PMID- 22469431
TI  - Effect of heavy metals on the stabilization of mercury(II) by DTCR in
      desulfurization solutions.
AB  - Several heavy metals, including Cu(2+), Ni(2+), Pb(2+), and Zn(2+), were
      investigated in simulated desulfurization solutions to evaluate their
      interferences with Hg(2+) during the reaction with dithiocarbamate type chelating
      resin (DTCR). Appropriate DTCR dosage and the effect of pH were also explored
      with respect to restoration of high Hg(2+) precipitation efficiency and reduction
      of mercury concentrations. The experimental results suggested that increasing
      heavy metal concentration inhibited Hg(2+) precipitation efficiency to a
      considerable extent and the inhibition order of the four heavy metals was
      Cu(2+)>Ni(2+)>Pb(2+)>Zn(2+). However, the coordination ability was closely
      related to the configuration and the orbital hybridization of each metal. In the
      cases of Cu(2+) and Pb(2+), increased DTCR dosage was beneficial to Hg(2+)
      precipitation, which could lay the foundation of practical applications of DTCR
      dosage for industrial wastewater treatment. The enhanced Hg(2+) precipitation
      performance seen for increasing pH might have come from the deprotonation of
      sulfur atoms on the DTCR functional groups and the formation of metal hydroxides
      (M(OH)(2), M=Cu, Pb, Hg).

PMID- 22469432
TI  - Increase in extraintestinal infections caused by Salmonella enterica subspecies
      II-IV.
AB  - To garner information regarding site of infection and age and sex of persons
      infected with Salmonella enterica subspecies II-IV, we retrospectively analyzed
      data on Salmonella spp. infections in California, USA, 1985-2009. These
      subspecies were found to cause significantly more frequent invasive disease
      (e.g., bacteremia) than did Salmonella subspecies I strains.

PMID- 22469433
TI  - Application of the near-infrared spectroscopy in the pharmaceutical technology.
AB  - Near-infrared (NIR) spectroscopy is currently the fastest-growing and the most
      versatile analytical method not only in the pharmaceutical sciences but also in
      the industry. This review focuses on recent NIR applications in the
      pharmaceutical technology. This article covers monitoring, by NIR, of many
      manufacturing processes, such as granulation, mixing or drying, in order to
      determine the end-point of these processes. In this paper, apart from basic
      theoretical information concerning the NIR spectra, there are included
      determinations of the quality and quantity of pharmaceutical compounds. Some
      examples of measurements and control of physicochemical parameters of the final
      medicinal products, such as hardness, porosity, thickness size, compression
      strength, disintegration time and potential counterfeit are included.
      Biotechnology and plant drug analysis using NIR is also described. Moreover, some
      disadvantages of this method are stressed and future perspectives are
      anticipated.

PMID- 22469434
TI  - A single serum dilution enzyme-linked immunosorbent assay for determining anti
      human papillomavirus (HPV) antibody titres in humans immunised with prophylactic
      HPV vaccines.
AB  - Two types of prophylactic human papillomavirus (HPV) vaccines are currently
      available. However, there is no simple monitoring system for assessing acquired
      immunity that can cope simultaneously with large numbers of serum samples.
      Approximately 30% of women with normal cytology are known to be seropositive for
      HPV types 16 and 18 because of the high prevalence of these HPV types. Therefore,
      to be useful the monitoring system has to discriminate clearly between vaccine
      recipients and other serology groups. However, there has never been any focus on
      developing a method to satisfy this condition. In this study, we developed a high
      throughput single-serum-dilution enzyme-linked immunoassay (ELISA) system for
      determining anti-HPV antibody titres following vaccination. We optimised the
      conditions for each ELISA step to increase its accuracy and precision and to
      avoid the high background of non-specific reactions that is a major problem for
      serology assays. The new ELISA system has superior linearity, accuracy and
      reproducibility. Moreover, it clearly discriminated between antibody levels in
      vaccine recipients and those in other serology groups such as individuals with
      normal cervical cytology and those with cervical cancer. Therefore, this single
      serum-dilution ELISA should be very useful for assessing the acquired immunity of
      HPV vaccine recipients.

PMID- 22469435
TI  - A novel marker of human endometrial mesenchymal stem-like cells.
AB  - Coexpression of CD140b (PDGFRbeta) and CD146 has been used to isolate endometrial
      mesenchymal stem-like cells (eMSCs), which have a perivascular location. This
      study aims to evaluate a single marker for purifying eMSCs. Using an antibody
      panel with novel specificities, we screened  human endometrial tissues and
      stromal cell suspensions by flow cytometry and immunohistochemistry to identify
      perivascular markers. Sorted subpopulations were examined for colony-forming unit
      (CFU), self-renewal, and differentiation assays for mesenchymal stem cell (MSC)
      function. We also  transplanted sorted eMSCs under the kidney capsule of
      superimmunodeficient NSG mice. Magnetic bead selection was compared with flow
      cytometry sorting (flow sorting) using CFU assay. One novel marker (W5C5) was
      particularly effective in selecting eMSCs. W5C5(+) cells comprise 4.2+/-0.6%  (n
      = 34) of endometrial stromal cells and reside predominantly in a perivascular
      location in both basal and functional layers of endometrium. The clonogenicity of
      W5C5(+) cells is significantly greater than W5C5(-) and unselected cells. W5C5(+)
      cells  differentiated into adipocytes, osteocytes, chondrocytes, myocytes, and
      endothelial cells. W5C5(+) cells produce endometrial stromal-like tissue in vivo.
      In terms of clonogenicity, magnetic bead-selected W5C5(+) cells gave rise to
      significantly higher CFU numbers compared  to flow-sorted W5C5(+) cells. This
      study identified W5C5 as a single marker capable of purifying eMSCs possessing
      MSC properties and reconstituting endometrial stromal tissues in vivo. W5C5
      enriches eMSCs to high purity and provides a simple protocol for their
      prospective isolation  using magnetic bead selection rather than flow sorting.
      W5C5 selection may provide an alternate, readily available autologous source of
      MSC, obtainable with minimal morbidity using an office endometrial biopsy
      procedure for future cell-based therapies.

PMID- 22469436
TI  - Prolonged KI polyomavirus infection in immunodeficient child.

PMID- 22469437
TI  - We call for iCAALL: International Collaboration for Asthma, Allergy and
      Immunology.

PMID- 22469438
TI  - Poor response to inhaled corticosteroids in obese, asthmatic patients.

PMID- 22469439
TI  - Exhaled nitric oxide in asthma management.

PMID- 22469440
TI  - Validating childhood symptoms with physician-diagnosed allergic rhinitis.
AB  - BACKGROUND: Multiple population-based and high-risk cohort studies use parental
      questionnaire responses to define allergic rhinitis (AR) in children. Individual
      questionnaire items have not been validated by comparison with physician
      diagnosed AR (PDAR). OBJECTIVE: To identify routine clinical questions that best
      agree with a physician diagnosis of AR and can be used for early case
      identification. METHODS: Children participating in a longitudinal birth cohort
      study were evaluated at ages 1 through 4 and at age 7 (n = 531) using
      questionnaires, physical examinations, and skin prick tests (SPT) with 15
      aeroallergens (AG). Parents answered 3 stem questions pertaining to their child,
      including presence of nasal symptoms absent a cold/flu (ISAAC-validated
      question), presence of hayfever, and ocular itch. Substem questions were answered
      with details regarding seasonality, nasal triggers, and ocular seasonality. A
      global assessment of allergic diseases, including AR, was performed by a
      specialty-trained clinician. Percent agreement, sensitivity, specificity, and
      positive predictive values were assessed for individual stem and substem
      questions. RESULTS: Positive response to having hayfever and presence of ocular
      symptoms had the highest specificity (84% and 69%, respectively) and the highest
      percent agreement (74% and 68%) with PDAR. Identification of triggers for nasal
      and ocular symptoms had the highest sensitivity (89%). Positive predictive values
      ranged from 31 to 39%. Combining 2 responses with highest agreement increased
      specificity for PDAR to 91%. CONCLUSION: Responses to hayfever and ocular
      symptoms had better specificity and percent agreement with PDAR than the ISAAC
      validated questionnaire item. Combining 2 rhinitis questions sharply increases
      specificity and may improve diagnostic accuracy of clinical questions.

PMID- 22469441
TI  - Characteristics of a patient population seeking medical advice for nasal symptoms
      in Bulgaria.
AB  - BACKGROUND: The proportion of patients visiting general practitioners (GPs),
      otorhinolaryngologists (ORLs), and allergologists (ALRGs) for nasal complaints is
      unknown but important in estimating the number of subjects with nasal symptoms
      bothersome enough to warrant physician consultations and assessing nasal
      pathological conditions' burden on a national health care system. OBJECTIVE: The
      Symptoms of Nasal Inconvenience Fact Finding (SNIFF) survey was developed to (1)
      assess incidence of physician visits attributable to nasal complaints; (2)
      characterize patients' nasal conditions; and (3) outline differences across
      physician categories. METHODS: The SNIFF survey was completed over 20 days by
      Bulgarian GPs, ORLs, and ALRGs whom patients consulted for nasal symptoms. Survey
      forms differentiated type and severity of patients' conditions according to
      Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and ranked
      bothersome symptoms. Smell impairment, comorbidities, and prescription practices
      were documented. RESULTS: Sixty-nine physicians (30 GPs, 8 ORLs, 31 ALRGs)
      completed 1,685 surveys. The proportion of patients with nasal symptoms over the
      total patients seen was 15.7%: ALRGs, 18.0%; GPs, 14.6%; ORLs, 13.1%. Patients
      were classified as having intermittent (38.8%) or persistent (61.2%) rhinitis,
      with most having moderate/severe symptoms (94.4%). Congestion was the leading
      symptom in 59.1%. Smell was impaired in 69.8% of patients, asthma was present in
      21.4%, and cough in 62.9%. ALRGs were more likely to diagnose and manage patients
      per ARIA guidelines than were ORLs or GPs. CONCLUSION: The SNIFF survey results
      demonstrate congestion's role as a leading symptom motivating patients to seek
      medical advice. SNIFF also uncovered differences in practices among different
      categories of health care providers.

PMID- 22469442
TI  - Does body mass index influence responsiveness to inhaled corticosteroids in
      persistent asthma?
AB  - BACKGROUND: Although the relationship between asthma and obesity has been
      extensively explored, the effect of body mass index (BMI) on the dose-response
      relationship to inhaled corticosteroids (ICS) has received little attention.
      OBJECTIVE: To assess the dose-response of inhaled budesonide on outcome measures
      of asthma between overweight and normal weight patients with persistent asthma.
      METHODS: Seventy-two patients with mild to moderate persistent asthma from a post
      hoc analysis of previously reported trial data were divided into 2 groups:
      overweight, BMI 25 kg/m(2) or higher; normal weight, BMI less than 25 kg/m(2).
      Each group received 4 weeks' treatment with inhaled (hydrofluoroalkane)
      budesonide 200 MUg/day then 800 MUg/day with ICS washout pretreatment. Outcome
      measures forced expiratory volume in 1 second (FEV(1)), fractional exhaled nitric
      oxide (FeNO), methacholine PC20, total daily asthma symptom score, and overnight
      urinary cortisol/creatinine ratio were performed at baseline and after each dose.
      RESULTS: Significantly greater improvements were seen in the normal weight group
      for both FeNO and symptom responses at 0 to 200 MUg and 0 to 800 MUg ICS doses
      (as change from baseline), compared with the overweight group: FeNO 0 to 200 MUg,
      P = .002; 0 to 800 MUg, P = .045; symptoms 0 to 200 MUg, P = .002; 0 to 800 MUg,
      P = .013. A trend also was seen toward attenuated cortisol suppression in
      overweight subjects at 0 to 800 MUg (P = .06), but no significant difference was
      seen at either dose in FEV(1) and methacholine PC20 between weight groups.
      CONCLUSION: Overweight patients with persistent asthma may have attenuated
      symptom and FeNO dose responses to inhaled budesonide compared with normal weight
      patients with asthma, with no differences in FEV(1) or methacholine PC20 between
      groups. Attenuated cortisol suppression in the overweight group may be the clue
      to this difference, alluding to reduced peripheral lung deposition or absorption
      in overweight patients with asthma.

PMID- 22469443
TI  - Sensitization to Per a 2 of the American cockroach correlates with more clinical
      severity among airway allergic patients in Taiwan.
AB  - BACKGROUND: In Taiwan, 57.5% of asthmatic patients are allergic to cockroaches,
      which are a major indoor allergen for immunoglobulin E (IgE)-mediated respiratory
      diseases. OBJECTIVE: To determine whether sensitization to different cockroach
      allergenic components correlates with different clinical manifestations and
      severities. METHODS: The complementary DNAs (cDNAs) encoding for Per a 1 through
      7 and Per a 9 were generated by reverse transcription polymerase chain reaction
      and cloned into the Escherichia coli expression system. Sixty-four subjects were
      divided into 3 groups based on the clinical severity of their allergic reaction:
      those with persistent asthma and rhinitis (AS), those with allergic rhinitis only
      (AR), and the nonallergic controls (NA). Serum levels of interleukin-8 (IL-8),
      monocyte chemotactic protein-1 (MCP-1), chemokine (C-C motif) ligand 20 (CCL-20),
      and granulocyte macrophage colony-stimulating factor (GM-CSF) were measured, and
      the binding frequencies to each recombinant allergen were examined. RESULTS:
      Serum levels of IL-8, MCP-1, and CCL-20 were significantly higher in the AS group
      than in the AR and NA groups. The numbers of IgE-binding allergens did not
      correlate with the clinical severity of airway allergy to cockroaches. However,
      81% in the AS group had IgE-binding activity to Per a 2, which was significantly
      higher than that of the AR group (45%, P < .05). In contrast, 80% of AR patients
      had IgE-binding activity to Per a 9 compared with only 28.5% of AS patients (P <
      .01). CONCLUSION: Allergens from American cockroaches do not have equal
      importance in terms of pathogenicity. Sensitization to Per a 2 correlates with
      more severe airway allergy and elevated proinflammatory chemokines. This may help
      in selecting target allergens for component resolved diagnosis and
      immunotherapeutic agents.

PMID- 22469444
TI  - Effect of exercise-induced bronchospasm and parental beliefs on physical activity
      of asthmatic adolescents from a tropical region.
AB  - BACKGROUND: Physical activity (PA) is an essential health promotion factor. In
      asthmatic children and adolescents, exercise-induced bronchospasm (EIB) and
      parental beliefs and attitudes toward PA may be limiting issues. OBJECTIVE: To
      compare PA levels in asthmatic adolescents with and without EIB and the influence
      of mothers' beliefs of asthma worsening due to PA and attitudes in restraining
      their children's PA, asthma severity, severe EIB, or bronchospasm perception.
      METHODS: We performed a cross-sectional, hypothesis-testing study from December
      1, 2008, through August 31, 2009, using the International Physical Activity
      Questionnaire to assesses PA levels in 134 asthmatic adolescents (10-19 years of
      age, 60% male) from an underprivileged community. EIB was defined as a decrease
      in forced expiratory volume in 1 second greater than 10% from basal 5, 15, or 30
      minutes after treadmill running for 8 minutes. Subjective factors were evaluated
      through specific questionnaires. RESULTS: EIB was diagnosed in 46% of patients
      and was not associated with lower PA levels (odds ratio, 1.62; 95% confidence
      interval, 0.75-3.52). The other factors evaluated were also not associated with
      lower PA levels, although 78% of the mothers said they believe asthmatic children
      cannot participate in PA as much as nonasthmatic children, 44% that exercise can
      be harmful, and 52% that they restrained their children's PA. CONCLUSION: We
      found no association between EIB and low PA levels, although EIB was a frequent
      event that should be addressed by health care professionals, along with mother's
      beliefs and attitudes toward PA.

PMID- 22469445
TI  - Uncontrolled asthma and factors related to morbidity in an impoverished, rural
      environment.
AB  - BACKGROUND: Asthma disproportionately affects children living in impoverished
      communities; however, factors related to asthma morbidity among impoverished
      rural children have not been adequately described. OBJECTIVE: To examine factors
      associated with asthma morbidity among rural children living in the Arkansas
      Delta region. METHODS: We performed a cross-sectional investigation of 109 rural
      children with asthma enrolled in public schools in the Arkansas Delta region. A
      questionnaire format and home inspection were used to examine participant,
      caregiver, and home characteristics. RESULTS: The median age of the study
      participants was 9 years, 83% were African American, and 71% had an annual
      household income of $20,000 or less. Ninety-eight percent of participants were
      insured, and most fit the criteria for uncontrolled asthma, yet only 23% reported
      taking inhaled corticosteroids. Transportation problems were cited by 20%. In the
      past 4 weeks, more than 50% reported rescue medication use or exercise
      limitations of 2 or more days per week or nocturnal symptoms of more than 2
      nights per month. Emergency department visits in the past 6 months were reported
      by 28%, and 43% reported an unscheduled physician's visits for asthma in the past
      3 months. Sixty-four percent had 1 or more positive allergen skin test results,
      and allergic sensitization was associated with exposure to dust mite, dog, mouse,
      and cockroach allergens in the home. CONCLUSION: Asthma morbidity was high among
      this cohort of atopic asthmatic children in the Arkansas Delta. Overuse of rescue
      medications and underuse of inhaled corticosteroids were prevalent even though
      the population was highly insured and had frequent health care use. Future asthma
      health initiatives should focus on the unique challenges associated with
      translating national guidelines-based care to rural pediatric populations. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00590304.

PMID- 22469446
TI  - Asthma action plans are highly variable and do not conform to best visual design
      practices.
AB  - BACKGROUND: Asthma action plans improve asthma outcomes and are recommended in
      guidelines. However, delivery by physicians and usage by patients remain low.
      This may be because of variability in existing plans and a failure to consider
      visual design and usability factors in plan development. OBJECTIVE: To
      characterize the variability in both the content and the format of existing
      plans, and the extent to which their format conforms to evidence-based visual
      design recommendations. METHODS: We collected plans from the internet, Canadian
      experts and associations, guidelines, and published trials. We inductively
      developed analytic criteria for format and content analyses. RESULTS: We
      collected 69 unique English or French-language adult outpatient plans from around
      the world. We found large variability in format, and plans fulfilled a mean of
      only 3.5 out of 8 evidence-based visual design recommendations. Content was also
      variable, including different descriptions of the baseline clinical state and
      descriptions and instructions at each "action point" (point recommending a change
      in treatment). CONCLUSION: Existing plans vary widely in content and format.
      Accordingly, studies evaluating the effectiveness of action plans may not be
      directly comparable. Also, visual design may affect usability, uptake, and
      effectiveness. Our results suggest that this has not been adequately addressed in
      most plans, and design evidence and experts should be included in future
      development.

PMID- 22469447
TI  - Factors associated with disparities in emergency department use among Latino
      children with asthma.
AB  - BACKGROUND: Significant disparities in emergency department (ED) rates exist for
      Latinos; however, few studies have investigated the factors that may account for
      these disparities. OBJECTIVES: To examine individual/family and health system
      factors among Latino and non-Latino white (NLW) children with asthma to explain
      disparities in ED rates. METHODS: The study was carried out in Puerto Rico (PR)
      and Rhode Island (RI) with the same design: a cross-sectional, observational
      approach with repeated measurements of selected variables. RESULTS: The sample
      was composed of 804 children ages 7 to 15 years, with 405 from PR and 399 from
      RI. Latino children from both sites had significantly higher rates of ED use as
      compared with NLWs from RI. Regression analyses showed site, asthma control,
      parental reported severity of asthma and public insurance to be significantly
      associated with ED use. CONCLUSION: Latino ethnicity and public insurance were
      among the most important factors related to frequent ED use. Revisions of the
      policies driving public insurance to assure better access to specialists,
      preventive education, and evidence-based treatment are needed. The results also
      suggest the need for the development of interventions in the ED that are geared
      toward educating families on how best to use emergency services.

PMID- 22469448
TI  - Correlation of anti-Pru p 3 IgE levels with severity of peach allergy reactions
      in children.
AB  - BACKGROUND: Peach allergy is regarded as one of the most important fresh fruit
      allergies. Data are available on the state-of-the-art diagnosis, including food
      challenges, and a component-resolved diagnosis. However, the roles played by
      different peach allergens with respect to symptom severity are not completely
      understood. OBJECTIVE: To evaluate the role of serum specific IgE to peach and
      recombinant allergens in the diagnosis of peach allergies in Italian children.
      METHODS: Forty-four children with peach allergy confirmed by a placebo-controlled
      food challenge were divided into 2 groups based on their symptom severity:
      patients with mild oral allergy syndrome (OAS) and patients with systemic
      symptoms (SS). The presence of specific IgE to peach and rPru p 1, rPru p 3, and
      rPru p 4 was determined. RESULTS: The presence of specific IgE to Pru p 4 and Pru
      p 1 was found significantly more frequently in patients with OAS, whereas
      specific IgE to Pru p 3 was not found significantly more frequently in patients
      with SS. Only anti-rPru p 4 IgE levels were significantly higher in patients with
      OAS, whereas no significant differences were found in anti-rPru p 1 and anti-rPru
      p 3 IgE levels between patients with OAS compared with patients with SS.
      CONCLUSION: In Italian children with peach allergies, the presence of specific
      IgE to Pru p 3 is not associated with SS, and the levels of specific IgE to Pru p
      3 do not correlate with the severity of the reactions.

PMID- 22469449
TI  - Mometasone furoate nasal spray increases the number of minimal-symptom days in
      patients with acute rhinosinusitis.
AB  - BACKGROUND: Acute rhinosinusitis (ARS) is triggered by viral or, uncommonly,
      bacterial infection, causing inflammatory symptoms for <=12 weeks. OBJECTIVE: To
      investigate effects of mometasone furoate nasal spray (MFNS) vs amoxicillin and
      placebo on minimal-symptom days. METHODS: A double-blind, parallel-group, placebo
      and active-controlled 15-day study randomly assigned patients 12 years of age or
      older to MFNS 200 MUg twice daily, MFNS 200 MUg once daily, amoxicillin 500 mg 3
      times daily, or placebo. Patients had baseline rhinosinusitis major symptom score
      (MSS; combined rhinorrhea, postnasal drip, congestion, sinus headache, facial
      pain) of >=5 and <=12 (maximum: 15) for 7 to 28 days; scores were similar among
      groups. Minimal-symptom days and minimal-congestion days were defined post hoc by
      average am/pm MSS <=4 and average AM/PM congestion <=1. RESULTS: MFNS twice daily
      (n = 234) showed more minimal-symptom days vs placebo (n = 246) (62.69% vs
      50.33%; P < .0001) or amoxicillin (n = 248) (54.35%; P = .0040). The MFNS QD was
      associated with numerically more minimal-symptom days than amoxicillin or placebo
      (54.72%; P <= .8982). MFNS was associated with more minimal-congestion days than
      placebo (72.97%, 67.73%, and 56.67% for twice daily, once daily, and placebo; P <
      .0001, each vs placebo) and MFNS BID with more minimal-congestion days than
      amoxicillin (72.97% vs 64.15%; P = .0007). Median time to first minimal-symptom
      day sustained until study end was 8.5 days for MFNS BID vs. 11 for placebo (P =
      .0085). CONCLUSION: MFNS 200 MUg twice daily significantly increased minimal
      symptom days vs amoxicillin or placebo in patients with ARS. Results of this
      intranasal corticosteroids (INS) therapy indicate it can improve outcomes and
      potentially reduce inappropriate antibiotic use.

PMID- 22469450
TI  - In vitro cytokine production after in vivo desensitization in an allopurinol
      induced delayed allergic reaction.

PMID- 22469451
TI  - Relationship of 25-hydroxyvitamin D and asthma control in children.

PMID- 22469452
TI  - Hypersensitivity reactions to marijuana.

PMID- 22469453
TI  - Anaphylaxis caused by tetrazepam without cross-reactivity with other
      benzodiazepines.

PMID- 22469454
TI  - Blood pressure monitoring in children undergoing food challenge: association with
      anaphylaxis.

PMID- 22469455
TI  - Basophil activation test in the diagnosis of gadobutrol anaphylaxis.

PMID- 22469457
TI  - Allergen of the month--sycamore maple.

PMID- 22469458
TI  - Biochemistry of mitochondria, life and intervention 2010.

PMID- 22469456
TI  - Environmental assessment and exposure control: a practice parameter--furry
      animals.

PMID- 22469460
TI  - Associations between visceral adipose tissue, inflammation and sex steroid
      concentrations in men.
AB  - CONTEXT: In men, obesity and the metabolic syndrome are accompanied by decreased
      testosterone levels, but little is known about the associations between visceral
      adipose tissue (VAT), VAT-related inflammation and sex steroids. OBJECTIVE: To
      examine the relative impact of VAT, abdominal subcutaneous adipose tissue (SAT)
      and interleukin 6 (IL-6), a marker of VAT-induced inflammation, on testosterone
      (T) and 17beta-oestradiol (E2) levels in dysmetabolic men. METHODS: We study the
      NUMEVOX cohort of 229 men, aged 27-77 years, who all had at least one metabolic
      syndrome criterion (on average three). IL-6, C-reactive protein, Homeostasis
      Model Assessment of (HOMA) insulin resistance index (HOMA-IR), liver enzymes, E2,
      LH, sex hormone-binding globulin (SHBG), T, waist circumference and body mass
      index (BMI) were measured; bioavailable testosterone (BT) was calculated from T
      and SHBG; MRI-assessed VAT and SAT were analysed in 109 of these men. RESULTS:
      Visceral adipose tissue was strongly correlated with E2 (Spearman r = 0.38, P <
      0.001) and with BT/E2 ratio (r = -0.42, P < 0.001), while SAT was not correlated
      with either. IL-6 was correlated with E2 (r = 0.19, P = 0.007), BT (r = -0.19, P
      = 0.006) and BT/E2 ratio (r = -0.30 P < 0.001). In multivariate linear analysis,
      the relation between VAT and E2 was independent of age, BMI (P = 0.008), leptin
      (P < 0.001), T and SHBG. Log(IL-6) was significantly inversely related with
      log(BT) (P = 0.032) independently of age, VAT, leptin and HOMA-IR. CONCLUSIONS:
      17beta-oestradiol levels were positively associated with VAT, but not with SAT,
      while T and BT were negatively and independently associated with IL-6. The
      significant inverse association between IL-6 and T suggests an important role of
      low-grade visceral fat inflammation in the central hypogonadism associated with
      the metabolic syndrome.

PMID- 22469461
TI  - Scimitar syndrome and azygos continuation of the inferior vena cava diagnosed in
      an adult--an unusual association.
AB  - Anormal drainage of the pulmonary veins into the inferior vena cava is known as
      scimitar syndrome. Scimitar syndrome often presents during infancy and rarely
      during adulthood, and the adult patients are mostly asymptomatic. It is usually
      in association with dextrocardia, hypoplasia of right lung, and congenital heart
      defects. However, interruption of inferior vena cava with azygous continuation is
      rarely associated with this syndrome.

PMID- 22469462
TI  - AutismPro system in supporting treatment of children with autism in Poland.
AB  - BACKGROUND: The efficacy of early intervention programs for children with autism
      has been emphasized in many studies. However, access for people with autism to
      professional services in Poland is very limited and the burden of supporting a
      child's development often falls on parents, especially in families with low
      socioeconomic status and families living far away from big cities. Using Internet
      resources in planning and delivering individualized intervention may be useful.
      This study examined the effects of a home program of intervention based on the
      AutismPro system with elements of consultative therapy. METHODS: Ten families of
      children with a diagnosis of autism participated in the project; nine of them
      completed the 6-month program of intervention. Parents were taught to use the
      AutismPro system and implement the intervention techniques in a home setting.
      Modification of the intervention program to suit individual children's needs and
      evaluations of children's progress were performed during consultation meetings
      with therapists. The pre- and post-treatment measurement of child development was
      performed using the Psychoeducational Profile - Revised (PEP-R). RESULTS:
      Children involved in the study progressed in total PEP-R scores and on the PEP-R
      subtest of fine motor, gross motor, non-verbal and verbal cognitive skills and
      eye-hand integration. Parents expressed positive opinions on the program.
      CONCLUSIONS: The results suggest that an intervention which combines the use of
      the Internet support tool and professional consultations may provide benefits to
      the children with autism. There are, however, methodological limitations of the
      study to be taken into account when interpreting the results.

PMID- 22469459
TI  - Comprehensive determinants of health service utilisation for mental health
      reasons in a Canadian catchment area.
AB  - INTRODUCTION: This study sought to identify factors associated with health
      service utilisation by individuals with mental disorders in a Canadian catchment
      area. METHODS: To be included in the study, participants had to be aged between
      15 and 65 and reside in the study location. Data was collected randomly from June
      to December 2009 by specially trained interviewers. A comprehensive set of
      variables (including geospatial factors) was studied using the Andersen's
      behavioural health service model. Univariate, bivariate, and multivariate
      analyses were carried out. RESULTS: Among 406 individuals diagnosed with mental
      disorders, 212 reported using a mental health service at least once in the 12
      months preceding the interviews. Emotional problems and a history of violence
      victimisation were most strongly associated with such utilisation. Participants
      who were middle-aged or deemed their mental health to be poor were also more
      likely to seek mental healthcare. Individuals living in neighbourhoods where
      rental accommodations were the norm used significantly fewer health services than
      individuals residing in neighbourhoods where homeownership was preponderant;
      males were also less likely to use services than females. CONCLUSIONS: Our study
      broke new ground by uncovering the impact of longstanding violence victimisation,
      and the proportion of homeownership on mental health service utilisation among
      this population. It also confirmed the prominence of some variables (gender, age,
      emotional problems and self-perceived mental health) as key enabling variables of
      health-seeking. There should be better promotion of strategies designed to change
      the attitudes of males and youths and to deal with violence victimisation. There
      is also a need for initiatives that are targeted to neighbourhoods where there is
      more rental housing.

PMID- 22469463
TI  - Cloning and characterization of the porcine IL-10 promoter.
AB  - Interleukin 10 (IL-10) is an anti-inflammatory and immunosuppressive cytokine
      that plays an important role in regulating the immune response. Therefore,
      understanding how IL-10 is regulated is important. The regulatory elements have
      been well studied in human and mouse promoters and several transcription factors
      have been showed to be involved in IL-10 transcription. In our study, a 1.5 kb
      fragment of the 5' flanking region of IL-10 gene was cloned and functionally
      characterized. Several putative regulatory elements including IRF, AP-1, Sp1,
      C/EBP, and STAT binding sites were found in the porcine IL-10 (pIL-10) promoter.
      The pIL-10 promoter deletion mutants were analyzed for their ability to direct
      luciferase expression in a porcine macrophage cell line (CRL 2843), human gastric
      carcinoma cell lines with or without Epstein-Barr virus (EBV), AGS-EBV and AGS
      cell lines. Our data showed that the minimal active pIL-10 promoter region was
      from -605 to +19, with the inducible activity requiring only one key DNA element,
      the Sp1 binding site (-398 to -393) upstream of the IL-10 gene starting point in
      both LPS-stimulated CRL 2843 and AGS-EBV cells. Moreover, our results suggested
      that the two IRF binding sites (-950 to -942 and -662 to -640) may have a
      positive role in the activation of the pIL-10 promoter in AGS-EBV cells, but not
      in LPS-stimulated CRL 2843 cells. These data implicate that the cloned porcine IL
      10 promoter could be used to explore the molecular mechanisms underlying the
      regulation of IL10 production in pigs.

PMID- 22469464
TI  - Barriers to conducting effective obstetric audit in Ifakara: a qualitative
      assessment in an under-resourced setting in Tanzania.
AB  - OBJECTIVE: To explore barriers to and solutions for effective implementation of
      obstetric audit at Saint Francis Designated District Hospital in Ifakara,
      Tanzania, where audit results have been disappointing 2 years after its
      introduction. METHODS: Qualitative study involving participative observation of
      audit sessions, followed by 23 in-depth interviews with health workers and
      managers. Knowledge and perceptions of audit were assessed and suggestions for
      improvement of the audit process explored. RESULTS: During the observational
      period, audit sessions were held irregularly and only when the head of department
      of obstetrics and gynaecology was available. Cases with evident substandard care
      factors were audited. In-depth interviews revealed inadequate knowledge of the
      purpose of audit, despite the fact that participants regarded obstetric audit as
      a potentially useful tool. Insufficient staff commitment, managerial support and
      human and material resources were mentioned as reasons for weak involvement of
      health workers and poor implementation of recommendations resulting from audit.
      Suggestions for improvement included enhancing feedback to all staff and managers
      to attend sessions and assist with the effectuation of audit recommendations.
      CONCLUSION: Obstetric staff in Ifakara see audit as an important tool for quality
      improvement. They recognise, however, that in their own situation, insufficient
      staff commitment and poor managerial support are barriers to successful
      implementation. They suggested training in concept and principles of audit as
      well as strengthening feedback of audit outcomes, to achieve structural health
      care improvements through audit.

PMID- 22469465
TI  - Neuroinvasive disease and West Nile virus infection, North Dakota, USA, 1999
      2008.
AB  - To determine risk for West Nile virus (WNV) neuroinvasive disease in North
      Dakota, we tested plasma samples from blood donors for WNV IgG and compared
      infection rates with reported WNV neuroinvasive disease incidence. We estimate
      that 1 in 244 WNV infections leads to neuroinvasive disease; risk is
      substantially increased among men and older persons.

PMID- 22469466
TI  - Determinants for autopsy after unexplained deaths possibly resulting from
      infectious causes, United States.
AB  - We analyzed US multiple cause-of-death data for 2003-2006 for demographic and
      clinical determinants for autopsy in unexplained deaths possibly resulting from
      infectious causes. For 96,242 deaths, the definition for unexplained death was
      met and autopsy status was recorded. Most decedents were male, 40-49 years of
      age, and white. To identify factors associated with unexplained death, we used
      data from Arizona records. Multivariate analysis of Arizona records suggested
      that decedents of races other than white and black and decedents who had
      clinicopathologic syndromes in the cardiovascular, sepsis/shock, and
      multisyndrome categories recorded on the death certificate were least likely to
      have undergone autopsy; children with unexplained death were the most likely to
      have undergone autopsy. Improved understanding of unexplained deaths can provide
      opportunities for further studies, strengthen collaboration between investigators
      of unexplained deaths, and improve knowledge and awareness of infectious diseases
      of public health concern.

PMID- 22469467
TI  - Crystal structures of multidrug-resistant HIV-1 protease in complex with two
      potent anti-malarial compounds.
AB  - Two potent inhibitors (compounds 1 and 2) of malarial aspartyl protease,
      plasmepsin-II, were evaluated against wild type (NL4-3) and multidrug-resistant
      clinical isolate 769 (MDR) variants of human immunodeficiency virus type-1 (HIV
      1) aspartyl protease. Enzyme inhibition assays showed that both 1 and 2 have
      better potency against NL4-3 than against MDR protease. Crystal structures of MDR
      protease in complex with 1 and 2 were solved and analyzed. Crystallographic
      analysis revealed that the MDR protease exhibits a typical wide-open conformation
      of the flaps (Gly48 to Gly52) causing an overall expansion in the active site
      cavity, which, in turn caused unstable binding of the inhibitors. Due to the
      expansion of the active site cavity, both compounds showed loss of direct
      contacts with the MDR protease compared to the docking models of NL4-3. Multiple
      water molecules showed a rich network of hydrogen bonds contributing to the
      stability of the ligand binding in the distorted binding pockets of the MDR
      protease in both crystal structures. Docking analysis of 1 and 2 showed a
      decrease in the binding affinity for both compounds against MDR supporting our
      structure-function studies. Thus, compounds 1 and 2 show promising inhibitory
      activity against HIV-1 protease variants and hence are good candidates for
      further development to enhance their potency against NL4-3 as well as MDR HIV-1
      protease variants.

PMID- 22469468
TI  - Inhibition of enterovirus 71 entry by transcription factor XBP1.
AB  - Inositol-requiring enzyme 1 (IRE1) plays an important role in the endoplasmic
      reticulum (ER), or unfolded protein, stress response by activating its downstream
      transcription factor X-box-binding protein 1 (XBP1). We demonstrated previously
      that enterovirus 71 (EV71) upregulated XBP1 mRNA levels but did not activate
      spliced XBP1 (XBP1s) mRNA or its downstream target genes, EDEM and chaperones. In
      this study, we investigated further this regulatory mechanism and found that IRE1
      was phosphorylated and activated after EV71 infection, whereas its downstream
      XBP1s protein level decreased. We also found that XBP1s was not cleaved directly
      by 2A(pro), but that cleavage of eukaryotic translation initiation factor 4G by
      the EV71 2A(pro) protein may contribute to the decrease in XBP1s expression.
      Knockdown of XBP1 increased viral protein expression, and the synthesis of EV71
      viral protein and the production of EV71 viral particles were inhibited in XBP1
      overexpressing RD cells. When incubated with replication-deficient and UV
      irradiated EV71, XBP1-overexpressing RD cells exhibited reduced viral RNA levels,
      suggesting that the inhibition of XBP1s by viral infection may underlie viral
      entry, which is required for viral replication. Our findings are the first
      indication of the ability of XBP1 to inhibit viral entry, possibly via its
      transcriptional activity in regulating molecules in the endocytic machinery.

PMID- 22469469
TI  - Galpha/LGN-mediated asymmetric spindle positioning does not lead to unequal
      cleavage of the mother cell in 3-D cultured MDCK cells.
AB  - The position of the mitotic spindle plays a key role in spatial control of cell
      division. It is generally believed that when a spindle is positioned
      asymmetrically in a dividing cell, the resulting daughter cells are usually
      unequal in size due to eccentric cleavage of the mother cell. Molecular
      mechanisms underlying the generation of unequal sized daughter cells have been
      extensively studied in Drosophila neuroblast and Caenorhabditis elegans zygote
      where the Galpha subunit of the heterotrimeric G proteins and its binding partner
      - Pins in Drosophila and GPR-1/2 in C. elegans - are shown to be critical in
      governing spindle positioning and asymmetric cleavage of the mother cell. In
      mammalian system, although Galpha and LGN (mammalian Pins homolog) are also
      required for spindle orientation, whether they can mediate asymmetric spindle
      positioning or asymmetric cleavage of the mother cell is not known. Here, by
      artificially targeting Galphai to the apical cortex in 3-D cultured MDCK cells,
      we established a system where asymmetric spindle positioning can be consistently
      induced. Interestingly, this asymmetrically positioned spindle does not lead to
      asymmetric cleavage; instead it results in equal sized daughter cells. Live cell
      time-lapse analysis revealed that anaphase spindle elongation compensated the
      original asymmetric spindle positioning. Our findings demonstrate that asymmetric
      spindle positioning does not necessarily lead to unequal sized daughter cells in
      mammalian system. We discuss potential mechanisms in generating unequal sized
      daughter cells.

PMID- 22469470
TI  - Sirtuin inhibition attenuates the production of inflammatory cytokines in
      lipopolysaccharide-stimulated macrophages.
AB  - In several inflammatory conditions such as rheumatoid arthritis or sepsis, the
      regulatory mechanisms of inflammation are inefficient and the excessive
      inflammatory response leads to damage to the host. Sirtuins are class III histone
      deacetylases that modulate the activity of several transcription factors that are
      implicated in immune responses. In this study, we evaluated the impact of sirtuin
      inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774
      macrophages by assessing the production of inflammatory cytokines. The
      pharmacologic inhibition of sirtuins decreased the production of tumour necrosis
      factor-alpha (TNF-alpha) interleukin 6 (IL-6) and Rantes. The reduction of
      cytokine production was associated with decreased nuclear factor kappa B (NF
      kappaB) activity and inhibitor kappa B alpha (IkappaBalpha) phosphorylation while
      no impact was observed on the phosphorylation status of p38 mitogen-activated
      kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a
      promising tool for the treatment of inflammatory conditions.

PMID- 22469471
TI  - How significant is the 'significant other'? Associations between significant
      others' health behaviors and attitudes and young adults' health outcomes.
AB  - BACKGROUND: Having a significant other has been shown to be protective against
      physical and psychological health conditions for adults. Less is known about the
      period of emerging young adulthood and associations between significant others'
      weight and weight-related health behaviors (e.g. healthy dietary intake, the
      frequency of physical activity, weight status). This study examined the
      association between significant others' health attitudes and behaviors regarding
      eating and physical activity and young adults' weight status, dietary intake, and
      physical activity. METHODS: This study uses data from Project EAT-III, a
      population-based cohort study with emerging young adults from diverse ethnic and
      socioeconomic backgrounds (n = 1212). Logistic regression models examining cross
      sectional associations, adjusted for sociodemographics and health behaviors five
      years earlier, were used to estimate predicted probabilities and calculate
      prevalence differences. RESULTS: Young adult women whose significant others had
      health promoting attitudes/behaviors were significantly less likely to be
      overweight/obese and were more likely to eat >= 5 fruits/vegetables per day and
      engage in >= 3.5 hours/week of physical activity, compared to women whose
      significant others did not have health promoting behaviors/attitudes. Young adult
      men whose significant other had health promoting behaviors/attitudes were more
      likely to engage in >= 3.5 hours/week of physical activity compared to men whose
      significant others did not have health promoting behaviors/attitudes.
      CONCLUSIONS: Findings suggest the protective nature of the significant other with
      regard to weight-related health behaviors of young adults, particularly for young
      adult women. Obesity prevention efforts should consider the importance of
      including the significant other in intervention efforts with young adult women
      and potentially men.

PMID- 22469472
TI  - Spontaneous coronary artery dissection in a young woman without risk factors.
AB  - BACKGROUND: Spontaneous coronary artery dissection is a very rare event and is
      more common in women than in men. Pregnancy and the early puerperium stage have
      been recognized as predisposing factors for this condition. CASE REPORT: A 33
      year-old woman presented to the Emergency Department (ED) with chest pain; the
      patient's electrocardiogram (ECG) showed an ST-segment elevation similar to that
      observed in ST-segment elevation myocardial infarction (STEMI). She experienced a
      ventricular fibrillation cardiac arrest when she was in the hospital and received
      resuscitation, after which she regained consciousness and showed spontaneous
      circulation. She underwent cardiac catheterization under the impression of
      spontaneous coronary artery dissection, and conservative therapy was chosen.
      CONCLUSION: In this report, we have underlined the importance of considering
      coronary artery dissection in the differential diagnosis of young women who
      present to the ED with chest pain, an ECG with ST-segment elevation, and very few
      cardiac risk factors.

PMID- 22469473
TI  - Competencies for practice in renal care: a national Delphi study.
AB  - The aim of this study was to describe essential competencies relevant for
      professional renal nursing in Sweden. A Delphi study with four rounds was
      conducted from November 2008 to April 2009. A national sample of renal nurses was
      used to achieve consensus about the core competencies required. The 43
      competencies were reviewed for face validity by external experts representing
      general nursing, renal nursing, stakeholders and nephrologists. The core
      competencies were categorised in nine areas according to their structure; nursing
      and medical science, information and teaching, examinations and therapies,
      promoting health and preventing ill health, palliative care, safety and quality,
      care environment, research and development and management and cooperation in the
      patient care pathway. Altogether these categories represent a national
      description of competence in renal nursing.

PMID- 22469474
TI  - Subclinical infections with Crimean-Congo hemorrhagic fever virus, Turkey.
AB  - To investigate Crimean-Congo hemorrhagic fever virus in Turkey, we conducted a
      seroepidemiologic survey during January-April 2009. Seroprevalence of infection
      was 10% in a sample from an outbreak region and increased with patient age,
      indicating that the virus had been previously present in Turkey. We also
      estimated that 88% of infections were subclinical.

PMID- 22469475
TI  - Anal fistula.

PMID- 22469476
TI  - Commentary on Gardenbroek et al.

PMID- 22469479
TI  - Routine preoperative chest computed tomography does not influence therapeutic
      strategy in patients with colorectal cancer.
AB  - AIM: Patients with lung metastasis from colorectal cancer (CRC) may benefit from
      surgical resection. Chest computed tomography (CT) is often included in the
      preoperative staging. Interpretation of the nature of pulmonary lesions is not
      always easy and many question its clinical value. METHOD: Clinical data for all
      patients treated at our institution for CRC have been collected prospectively in
      a dedicated database. Since August 2008 chest CT has been routinely performed for
      preoperative staging. The outcome of 147 patients operated on since then (Group
      A) was compared with a numerically equal group of patients (147) (Group B)
      treated before the introduction of preoperative routine chest CT. RESULTS:
      Pulmonary lesions were identified in 45 (30%) patients in Group A and 10 (6.8%)
      in Group B. Ten and nine lesions, respectively, were interpreted as metastases.
      In 28 (19%) patients in Group A, the lesions were considered to be indeterminate
      and only four were confirmed as malignant. Overall metastases were present after
      1 year of follow-up in 5 (50%) of 10 patients in Group A and 5 (55%) of 9 in
      Group B. The global incidence of synchronous and metachronous metastases was
      6.8%, with no statistical difference between the two groups. CONCLUSION: This
      study shows that chest CT reveals a higher number of pulmonary lesions, only a
      small proportion of which were malignant. The investigation does not add value to
      routine staging methods in patients with CRC.

PMID- 22469481
TI  - Development of a social morbidity score in patients with chronic ulcerative
      colitis as a potential guide to treatment.
AB  - AIM: Present quality of life instruments for inflammatory bowel disease do not
      evaluate many social aspects of patients' lives that are potentially important in
      clinical decision making. We have developed a new Social Impact of Chronic
      Conditions - Inflammatory Bowel Disease (SICC-IBD) questionnaire to assess these
      areas. METHOD: A 34-item questionnaire was piloted to determine quality of life
      relating to education, personal relationships, employment, independence and
      finance. It was compared with the Short Form 36-Item version 2 (SF-36v2) and the
      Inflammatory Bowel Disease Questionnaire (IBDQ) in 150 patients with chronic
      ulcerative colitis on an endoscopic surveillance register who had never had
      surgery. RESULTS: Reliability and validity testing enabled the questionnaire to
      be shortened to only eight items. There was a high level of reliability
      (Cronbach's alpha=0.72). The questionnaire correlated well with the social
      functioning domain of the SF-36 (rs=0.56) and was able to distinguish clinical
      severity of disease. CONCLUSION: The SICC-IBD is a new tool for assessment of
      patients with ulcerative colitis, which has identified new aspects of social
      disability for further study and for potential use as an additional tool in
      therapy decisions.

PMID- 22469480
TI  - MUTYH hotspot mutations in unselected colonoscopy patients.
AB  - AIM: Biallelic MutY human homologue (MUTYH) germline mutations predispose to
      recessively inherited adenomatous polyposis, designated MUTYH-associated
      polyposis (MAP), and colorectal cancer (CRC). The hotspot mutations p.Y179C and
      p.G396D account for the majority of pathogenic variants of MUTYH in Caucasians.
      Our aim was to evaluate the prevalence of MUTYH mutations in a prospective cohort
      of unselected patients with different colorectal diseases. METHOD: The hotspot
      mutations p.Y179C and p.G396D were genotyped in 352 consecutive patients
      undergoing colonoscopy at our tertiary referral centre. Exons 2-14 were sequenced
      in hotspot mutation carriers to exclude additional variants. RESULTS: Overall, we
      identified five heterozygous p.Y179C mutations and three heterozygous p.G396D
      mutations in seven hotspot mutation carriers (risk allele frequencies 0.7% and
      0.4%, respectively). Two of these hotspot mutation carriers harboured a
      heterozygous p.Q338H variant, which is of uncertain clinical significance, on the
      other allele. Three individuals were biallelic MUTYH variant carriers
      (p.Y179C/p.G382D: typical MAP; p.Y179C/p.Q338H: atypical MAP with late onset and
      lower polyp burden; p.G382D/p.Q338H: inflammatory bowel disease), and four
      subjects were monoallelic mutation carriers. CONCLUSION: MUTYH-associated
      disease, and hence genetic counselling and MUTYH genetic testing, should be
      considered in the clinical routine of an endoscopy unit, but the wide range of
      phenotypes represents a challenge for patient identification. The clinical
      significance of p.Q338H should be evaluated in future case-control studies
      because compound heterozygotes for pathogenic mutations and p.Q338H may be at
      increased risk for mild polyposis or CRC. In addition, MUTYH should be assessed
      as a potential susceptibility gene for the development of colitis-associated CRC
      in future.

PMID- 22469482
TI  - Musosal tumour necrosis factor alpha in diverticular disease of the colon is
      overexpressed with disease severity.
AB  - AIM: Inflammation occurs in diverticular disease (DD), but there is little
      information on inflammatory cytokines such as tumour necrosis factor alpha (TNF
      alpha). The aim of this study was to assess TNF-alpha expression in DD and to see
      whether it is related to the severity of the disease. METHOD: Twenty-four
      patients with symptomatic DD were divided into those with acute uncomplicated
      diverticulitis (AUD) (12 patients) and those with symptomatic uncomplicated
      diverticular disease (SUDD) (12 patients). Twelve further patients with
      asymptomatic diverticulosis (AD), six with segmental colitis associated with
      diverticulosis (SCAD), with ulcerative colitis (UC) and six healthy individuals
      (HC) were enrolled as controls. TNF-alpha expression in the colonic mucosa was
      assessed by the amount of mRNA codifying for the synthesis of TNF-alpha. RESULTS:
      TNF-alpha expression was significantly higher in AUD than in HC (P=0.0007), in AD
      (P=0.0001) and in SUDD (P=0.0179). It was significantly higher also in SUDD than
      in HC (P=0.0007) and in AD (P=0.0001). TNF-alpha expression in AUD did not differ
      significantly from that in UC (P=0.0678) and SCAD (P=0.0610). It was
      significantly higher in UC, SCAD and AUD than in SUDD (P=0.0007, P=0.0001,
      P=0.0179). CONCLUSION: TNF-alpha expression in DD seems to be related to the
      severity of the disease. In particular, it appears to be overexpressed in DD with
      inflammation (AUD and SUDD) compared with DD without (AD).

PMID- 22469483
TI  - LMP-420, a small molecular inhibitor of TNF-alpha, prolongs islet allograft
      survival by induction of suppressor of cytokine signaling-1: synergistic effect
      with cyclosporin-A.
AB  - Inflammatory insults following islet transplantation (ITx) hinders engraftment
      and long-term function of the transplanted (Tx) islets. Using a murine model of
      ITx, we determined the role of LMP-420, a novel TNF-alpha inhibitor, both
      individually and in combination with the immunosuppressant  cyclosporine A (CSA)
      in islet engraftment and survival. Diabetic C57BL/6 mice were Tx with 500 BALB/c
      islets under the kidney capsule. Four cohorts were used: LMP-420 only, CSA only,
      combination of LMP-420 and CSA (LMP+CSA), and control (n = 12 per cohort). Serial
      monitoring of blood  glucose levels revealed that LMP+CSA (35 +/- 5 days)
      prolonged stable blood insulin levels compared to control (6 +/- 4 days).
      Immunohistology demonstrated that coadministration (LMP+CSA) results in a
      significant decrease in CD8(+) T-cell infiltration (LMP+CSA: 31 +/-  18 vs.
      control: 224 +/- 51 cells, p < 0.001). Serum cytokine analysis revealed that LMP
      420 administration resulted in an increase in the anti-inflammatory cytokine IL
      10 (2.5-fold), and a decrease in TNF-alpha (threefold) with no change in IL-2.
      However, coadministration  resulted in a marked decrease in both IL-2 and TNF
      alpha (threefold) along with increase in IL-10 (threefold). Coadministration also
      demonstrated increase of antiapoptotic SOCS-1 and Mn-SOD expression and
      significant reduction of donor-specific antibodies (p < 0.005). In conclusion, 
      LMP-420 administration with CSA results in the upregulation of anti-inflammatory
      and antiapoptotic mechanisms which facilitate islet allograft engraftment and
      survival.

PMID- 22469484
TI  - Quantifying the sources of variability in equine faecal egg counts: implications
      for improving the utility of the method.
AB  - The faecal egg count (FEC) is the most widely used means of quantifying the
      nematode burden of horses, and is frequently used in clinical practice to inform
      treatment and prevention. The statistical process underlying the FEC is complex,
      comprising a Poisson counting error process for each sample, compounded with an
      underlying continuous distribution of means between samples. Being able to
      quantify the sources of variability contributing to this distribution of means is
      a necessary step towards providing estimates of statistical power for future FEC
      and FECRT studies, and may help to improve the usefulness of the FEC technique by
      identifying and minimising unwanted sources of variability. Obtaining such
      estimates require a hierarchical statistical model coupled with repeated FEC
      observations from a single animal over a short period of time. Here, we use this
      approach to provide the first comparative estimate of multiple sources of within
      horse FEC variability. The results demonstrate that a substantial proportion of
      the observed variation in FEC between horses occurs as a result of variation in
      FEC within an animal, with the major sources being aggregation of eggs within
      faeces and variation in egg concentration between faecal piles. The McMaster
      procedure itself is associated with a comparatively small coefficient of
      variation, and is therefore highly repeatable when a sufficiently large number of
      eggs are observed to reduce the error associated with the counting process. We
      conclude that the variation between samples taken from the same animal is
      substantial, but can be reduced through the use of larger homogenised faecal
      samples. Estimates are provided for the coefficient of variation (cv) associated
      with each within animal source of variability in observed FEC, allowing the
      usefulness of individual FEC to be quantified, and providing a basis for future
      FEC and FECRT studies.

PMID- 22469485
TI  - Update on infectious risks associated with dental unit waterlines.
AB  - Modern dental chair units consist of a network of interconnected narrow-bore
      plastic tubes called dental unit waterlines (DUWLs). The water delivered by these
      DUWLs acts as both a coolant for a range of instruments and an irrigant during
      dental treatments. The quality of water is of considerable importance because
      both patients and dental team are regularly exposed to water and aerosols
      generated by dental equipment. Studies have demonstrated that DUWLs provide a
      favourable environment for microbial proliferation and biofilm formation, and
      that water is consequently often contaminated with high densities of various
      microorganisms (bacteria, fungi, protozoa, viruses). The presence of high levels
      of microbial contamination may be a health problem for dentists and patients,
      especially those who are immunocompromised. The current status of knowledge on
      microbial contamination of DUWLs is presented, with an emphasis on the infectious
      risk associated with DUWLs and on the various approaches for disinfecting and
      protecting DUWLs.

PMID- 22469486
TI  - Advances in geocoding for the health sciences.

PMID- 22469487
TI  - A research agenda: does geocoding positional error matter in health GIS studies?
AB  - Until recently, little attention has been paid to geocoding positional accuracy
      and its impacts on accessibility measures; estimates of disease rates; findings
      of disease clustering; spatial prediction and modeling of health outcomes; and
      estimates of individual exposures based on geographic proximity to pollutant and
      pathogen sources. It is now clear that positional errors can result in flawed
      findings and poor public health decisions. Yet the current state-of-practice is
      to ignore geocoding positional uncertainty, primarily because of a lack of
      theory, methods and tools for quantifying, modeling, and adjusting for geocoding
      positional errors in health analysis. This paper proposes a research agenda to
      address this need. It summarizes the basics of the geocoding process, its
      assumptions, and empirical evidence describing the magnitude of geocoding
      positional error. An overview of the impacts of positional error in health
      analysis, including accessibility, disease clustering, exposure reconstruction,
      and spatial weights estimation is presented. The proposed research agenda
      addresses five key needs: (1) a lack of standardized, open-access geocoding
      resources for use in health research; (2) a lack of geocoding validation datasets
      that will allow the evaluation of alternative geocoding engines and procedures;
      (3) a lack of spatially explicit geocoding positional error models; (4) a lack of
      resources for assessing the sensitivity of spatial analysis results to geocoding
      positional error; (5) a lack of demonstration studies that illustrate the
      sensitivity of health policy decisions to geocoding positional error.

PMID- 22469488
TI  - Investigating impacts of positional error on potential health care accessibility.
AB  - Accessibility to health services at the local or community level is an effective
      approach to measuring health care delivery in various constituencies in Canada
      and the United States. GIS and spatial methods play an important role in
      measuring potential access to health services. The Three-Step Floating Catchment
      Area (3SFCA) method is a GIS based procedure developed to calculate potential
      (spatial) accessibility as a ratio of primary health care (PHC) providers to the
      surrounding population in urban settings. This method uses PHC provider locations
      in textual/address format supplied by local, regional, or national health
      authorities. An automated geocoding procedure is normally used to convert such
      addresses to a pair of geographic coordinates. The accuracy of geocoding depends
      on the type of reference data and the amount of value-added effort applied. This
      research investigates the success and accuracy of six geocoding methods as well
      as how geocoding error affects the 3SFCA method. ArcGIS software is used for
      geocoding and spatial accessibility estimation. Results will focus on two
      implications of geocoding: (1) the success and accuracy of different automated
      and value-added geocoding; and (2) the implications of these geocoding methods
      for GIS-based methods that generalise results based on location data.

PMID- 22469489
TI  - Spatial error in geocoding physician location data from the AMA Physician
      Masterfile: implications for spatial accessibility analysis.
AB  - The accuracy of geocoding hinges on the quality of address information that
      serves as input to the geocoding process; however errors associated with poor
      address quality are rarely studied. This paper examines spatial errors that arise
      due to incorrect address information with respect to physician location data in
      the United States. Studies of spatial accessibility to physicians in the U.S.
      typically rely on data from the American Medical Association's Physician
      Masterfile. These data are problematic because a substantial proportion of
      physicians only report a mailing address, which is often the physician's home
      (residential) location, rather than the address for the location where health
      care is provided. The incorrect geocoding of physicians' practice locations based
      on inappropriate address information results in a form of geocoding error that
      has not been widely analyzed. Using data for the Chicago metropolitan region, we
      analyze the extent and implications of geocoding error for measurement of spatial
      accessibility to primary care physicians. We geocode the locations of primary
      care physicians based on mailing addresses and office addresses. The spatial
      mismatch between the two is computed at the county, zip code and point location
      scales. Although mailing and office address locations are quite close for many
      physicians, they are far apart (>20 km) for a substantial minority. Kernel
      density estimation is used to characterize the spatial distribution of physicians
      based on office and mailing addresses and to identify areas of high spatial
      mismatch between the two. Errors are socially and geographically uneven,
      resulting in overestimation of physician supply in some high-income suburban
      communities, and underestimation in certain central city locations where health
      facilities are concentrated. The resulting errors affect local measures of
      spatial accessibility to primary care, biasing statistical analyses of the
      associations between spatial access to care and health outcomes.

PMID- 22469490
TI  - The effect of administrative boundaries and geocoding error on cancer rates in
      California.
AB  - Geocoding is often used to produce maps of disease rates from the diagnosis
      addresses of incident cases to assist with disease surveillance, prevention, and
      control. In this process, diagnosis addresses are converted into
      latitude/longitude pairs which are then aggregated to produce rates at varying
      geographic scales such as Census tracts, neighborhoods, cities, counties, and
      states. The specific techniques used within geocoding systems have an impact on
      where the output geocode is located and can therefore have an effect on the
      derivation of disease rates at different geographic aggregations. This paper
      investigates how county-level cancer rates are affected by the choice of
      interpolation method when case data are geocoded to the ZIP code level. Four
      commonly used areal unit interpolation techniques are applied and the output of
      each is used to compute crude county-level five-year incidence rates of all
      cancers in California. We found that the rates observed for 44 out of the 58
      counties in California vary based on which interpolation method is used, with
      rates in some counties increasing by nearly 400% between interpolation methods.

PMID- 22469491
TI  - Quantifying the magnitude of environmental exposure misclassification when using
      imprecise address proxies in public health research.
AB  - In spatial epidemiologic and public health research it is common to use spatially
      aggregated units such as centroids of postal/zip codes, census tracts,
      dissemination areas, blocks or block groups as proxies for sample unit locations.
      Few studies, however, address the potential problems associated with using these
      units as address proxies. The purpose of this study is to quantify the magnitude
      of distance errors and accessibility misclassification that result from using
      several commonly-used address proxies in public health research. The impact of
      these positional discrepancies for spatial epidemiology is illustrated by
      examining misclassification of accessibility to several health-related
      facilities, including hospitals, public recreation spaces, schools, grocery
      stores, and junk food retailers throughout the City of London and Middlesex
      County, Ontario, Canada. Positional errors are quantified by multiple
      neighborhood types, revealing that address proxies are most problematic when used
      to represent residential locations in small towns and rural areas compared to
      suburban and urban areas. Findings indicate that the shorter the threshold
      distance used to measure accessibility between subject population and health
      related facility, the greater the proportion of misclassified addresses. Using
      address proxies based on large aggregated units such as centroids of census
      tracts or dissemination areas can result in very large positional discrepancies
      (median errors up to 343 and 2088 m in urban and rural areas, respectively), and
      therefore should be avoided in spatial epidemiologic research. Even smaller,
      commonly-used, proxies for residential address such as postal code centroids can
      have large positional discrepancies (median errors up to 109 and 1363 m in urban
      and rural areas, respectively), and are prone to misrepresenting accessibility in
      small towns and rural Canada; therefore, postal codes should only be used with
      caution in spatial epidemiologic research.

PMID- 22469492
TI  - Error propagation models to examine the effects of geocoding quality on spatial
      analysis of individual-level datasets.
AB  - The quality of geocoding has received substantial attention in recent years. A
      synthesis of published studies shows that the positional errors of street
      geocoding are somewhat unique relative to those of other types of spatial data:
      (1) the magnitude of error varies strongly across urban-rural gradients; (2) the
      direction of error is not uniform, but strongly associated with the properties of
      local street segments; (3) the distribution of errors does not follow a normal
      distribution, but is highly skewed and characterized by a substantial number of
      very large error values; and (4) the magnitude of error is spatially
      autocorrelated and is related to properties of the reference data. This makes it
      difficult to employ analytic approaches or Monte Carlo simulations for error
      propagation modeling because these rely on generalized statistical
      characteristics. The current paper describes an alternative empirical approach to
      error propagation modeling for geocoded data and illustrates its implementation
      using three different case-studies of geocoded individual-level datasets. The
      first case-study consists of determining the land cover categories associated
      with geocoded addresses using a point-in-raster overlay. The second case-study
      consists of a local hotspot characterization using kernel density analysis of
      geocoded addresses. The third case-study consists of a spatial data aggregation
      using enumeration areas of varying spatial resolution. For each case-study a high
      quality reference scenario based on address points forms the basis for the
      analysis, which is then compared to the result of various street geocoding
      techniques. Results show that the unique nature of the positional error of street
      geocoding introduces substantial noise in the result of spatial analysis,
      including a substantial amount of bias for some analysis scenarios. This confirms
      findings from earlier studies, but expands these to a wider range of analytical
      techniques.

PMID- 22469493
TI  - Geostatistical analysis of health data with different levels of spatial
      aggregation.
AB  - This paper presents a geostatistical approach to combine two geographical sets of
      area-based data into the mapping of disease risk, with an application to the rate
      of prostate cancer late-stage diagnosis in North Florida. This methodology is
      used to combine individual-level data assigned to census tracts for
      confidentiality reasons with individual-level data that were allocated to ZIP
      codes because of incomplete geocoding. This form of binomial kriging, which
      accounts for the population size and shape of each geographical unit, can
      generate choropleth or isopleth risk maps that are all coherent through spatial
      aggregation. Incorporation of both types of areal data reduces the loss of
      information associated with incomplete geocoding, leading to maps of risk
      estimates that are globally less smooth and with smaller prediction error
      variance.

PMID- 22469494
TI  - Alphaproteobacterial communities in geographically distant populations of the
      lichen Cetraria aculeata.
AB  - Lichen symbioses were recently shown to include diverse bacterial communities.
      Although the biogeography of lichen species is fairly well known, the patterns of
      their bacterial associates are relatively poorly understood. Here we analyse the
      composition of Alphaproteobacteria in Cetraria aculeata, a common lichen species
      that occurs at high latitudes and various habitats. Using clone libraries we show
      that most of the associated Alphaproteobacteria belong to Acetobacteraceae, which
      have also been found previously in other lichen species of acidic soils and rocks
      in alpine habitats. The majority of alphaproteobacterial sequences from C.
      aculeata are very similar to each other and form a single clade. Data from C.
      aculeata reveal that alphaproteobacterial communities of high latitudes are
      depauperate and more closely related to each other than to those of extrapolar
      habitats. This agrees with previous findings for the fungal and algal symbiont in
      this lichen. Similar to the algal partner, the composition of lichen
      alphaproteobacterial communities is affected by environmental parameters.

PMID- 22469495
TI  - Peri-operative complications after adenotonsillectomy in a UK pediatric tertiary
      referral centre.
AB  - OBJECTIVES: Adenoidectomy and/or tonsillectomy are commonly performed in tertiary
      pediatric hospitals for the management of obstructive sleep apnea, often in
      children with significant comorbidities. This study examines the peri-operative
      course of a large series of complex patients undergoing such surgery at a major
      pediatric centre, reporting particularly cases of respiratory compromise
      requiring intensive care admission, both electively and unplanned. METHODS: This
      study was conducted by the pediatric ENT department at Great Ormond Street
      Hospital. All children undergoing adenoidectomy and/or tonsillectomy from July
      2003 to December 2010 were included in this study. This involved a retrospective
      review of the case notes and hospital databases, with particular emphasis on
      those children requiring admission to the pediatric intensive care unit. RESULTS:
      A total of 1735 consecutive admissions for adenoidectomy and/or tonsillectomy
      (1627 individual patients aged 4-197 months, median 46 months) were included
      between 2003 and 2010 (998 adenotonsillectomies, 182 tonsillectomies and 555
      adenoidectomies). In this group, 999/1627 patients (61.4%) had a diagnosis of
      sleep disordered breathing or sleep apnea, including 258 who had polysomnography.
      407/1627 (25.0%) had no specific comorbidities which were felt likely to
      influence their surgical outcome. Established high risk factors included age less
      than 24 months (292), Down syndrome (99), neuromuscular problems (314),
      craniofacial abnormalities (94), storage diseases (23), morbid obesity (20),
      cardiovascular disease (133), respiratory disease (261), hemoglobinopathy (76)
      and coagulophathy (34). 300/1735 admissions were day cases and 1082/1735 were
      observed for one night. 353/1735 required more than one night in hospital (294
      for two to three nights). 7/1735 had primary hemorrhage necessitating return to
      the operating room, all after tonsillectomy. 41/1735 (38 with major
      comorbidities) required peri-operative intensive care admission, mostly for
      respiratory support. Of these, 7 were admitted pre-operatively to intensive care,
      and 17 were planned post-operative transfers. Only 17/1735 required unanticipated
      post-operative admission to intensive care. Odds ratio analysis suggested a
      significantly higher chance of PICU admission in children with particular
      comorbidities (Down Syndrome, cardiac disease, obesity, cerebral palsy,
      craniofacial anomalies, mucopolysaccharidoses and hemoglobinopathy) when compared
      to children without comorbidities. Adenotonsillectomy was associated with a
      higher risk of PICU admission than adenoidectomy alone, but patient age less than
      24 months was not associated with significantly higher rates of PICU admission.
      There were no peri-operative mortalities in this cohort. CONCLUSIONS: The peri
      operative course was largely uneventful for the majority of children undergoing
      surgery during this period, particularly given the high prevalence of sleep apnea
      and other risk factors in this cohort. Major complications were uncommon, with
      2.4% of these selected, typically high risk cases requiring peri-operative
      intensive care admission. Importantly, only 1% of all admissions required
      unanticipated transfer to intensive care. This has informed changes in peri
      operative management in this unit, with implications for other pediatric tertiary
      referral centres.

PMID- 22469496
TI  - Antigen persistence of rapid diagnostic tests in pregnant women in Nanoro,
      Burkina Faso, and the implications for the diagnosis of malaria in pregnancy.
AB  - OBJECTIVES: To evaluate persistence of several Plasmodium antigens in pregnant
      women after treatment and compare diagnostics during treatment follow-up.
      METHODS: Thirty-two pregnant women (N = 32) with confirmed malaria infection by a
      histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) and microscopy
      were followed for 28 days after artemisinin-based combination therapy (ACT). A
      Plasmodium lactate dehydrogenase (pLDH)-based RDT and two ELISAs based on the
      detection of dihydrofolate reductase-thymidylate synthase (DHFR-TS) and haeme
      detoxification protein (HDP) were compared with each other and to RT-PCR at each
      visit. RESULTS: The mean visit number (95% confidence interval) on which the HRP2
      based RDT was still positive after treatment was 3.4 (2.7-4.1) visits with some
      patients still positive at day 28. This is significantly later than the pLDH
      based RDT [0.84 (0.55-1.1)], microscopy (median 1, range 1-3), DHFR-TS-ELISA [1.7
      (1.1-2.3)] and RT-PCR (median 2, range 1-5) (P < 0.05), but not significantly
      later than HDP-ELISA [2.1 (1.6-2.7)]. Lower gravidity and higher parasite density
      at day 0 resulted in significantly longer positive results with most tests (P <
      0.05). CONCLUSIONS: HRP2 can persist up to 28 days after ACT treatment;
      therefore, this test is not suitable for treatment follow-up in pregnant women
      and can generate problems when using this test during intermittent preventive
      treatment (IPTp). DHFR-TS is less persistent than HRP2, making it a potentially
      interesting target for diagnosis.

PMID- 22469497
TI  - High virulence of African swine fever virus caucasus isolate in European wild
      boars of all ages.

PMID- 22469498
TI  - Outcome of fetal echocardiography: a 17 year single-institution experience in
      Japan.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate the influence of
      prenatal diagnosis on perinatal outcomes of congenital heart disease (CHD) over a
      17 year period at a single center. METHODS: The perinatal outcome of CHD in 146
      patients diagnosed on fetal echocardiography between 1994 and 2010 were reviewed.
      The characteristics of 193 neonatal inpatients with CHD treated at the authors'
      department between 2001 and 2010 were also analyzed; among the inpatients, 61
      were diagnosed before birth (prenatal group) and 132 were diagnosed after birth
      (postnatal group). RESULTS: Among the 146 patients prenatally diagnosed with CHD,
      the prenatal mortality, including abortion and stillbirth, decreased from 1994 to
      2010. Among the 193 neonatal inpatients, the prenatal group had lower gestational
      age and bodyweight than the postnatal group. Further, the prenatal group had
      lower blood pH at admission, but no patient in that group experienced ductal
      shock, although six patients in the postnatal group did. The average dose of
      prostaglandin E1 used in duct-dependent CHD was significantly lower in the
      prenatal group than in the postnatal group (3.4 vs. 4.6 ng/kg per min; P =
      0.015). CONCLUSIONS: Prenatal diagnosis of CHD enables planned labor, prevents
      ductal shock, and reduces prostaglandin E1 side-effects and medical expenditure.

PMID- 22469499
TI  - Hepatic miR-29ab1 expression modulates chronic hepatic injury.
AB  - MicroRNAs (miRNAs) are small, regulatory non-coding RNAs that have potent effects
      on gene expression. Several miRNA are deregulated in cellular processes involved
      in human liver diseases and regulation of cellular processes. Recent studies have
      identified the involvement of miR-29 in hepatic fibrosis and carcinogenesis.
      Although several targets of miR-29 have been identified, there is limited
      information regarding the cell-type specific roles of miR-29 in the liver, and we
      sought to evaluate the role of this miRNA in hepatic pathobiology. We report the
      generation of a tissue-specific knockout mouse to evaluate the role of miR-29 in
      hepatic fibrosis and carcinogenesis in response to injury. We hypothesized that
      miR-29 contributes to the hepatocyte driven response to chronic cellular injury
      that results in fibrosis. In support of this hypothesis, fibrosis and mortality
      were enhanced in miR29 knockout mice in response to carbon tetrachloride. Genome
      wide gene expression analysis identified an over-representation of genes
      associated with fibrosis. The oncofetal RNA H19 was modulated in a miR-29
      dependent manner following exposure to carbon tetrachloride in vivo. The impact
      of a hepatocyte specific miR-29 knockout on survival following chronic hepatic
      injury in vivo implicates this miRNA as a potential target for intervention.
      These results provide evidence of the involvement of miR-29 in chronic hepatic
      injury, and suggest a role for deregulated hepatocyte expression of miR-29 in the
      response to hepatic injury, fibrosis and carcinogenesis.

PMID- 22469500
TI  - DNA fragmentation dynamics allows the assessment of cryptic sperm damage in
      human: evaluation of exposure to ionizing radiation, hyperthermia, acidic pH and
      nitric oxide.
AB  - Sperm DNA fragmentation (SDF) is not a static seminal parameter, since the
      longevity of sperm DNA decreases progressively with time following ejaculation or
      thawing. While the dynamics of SDF is a species-specific characteristic, in the
      case of humans, there is still significant variation within patients. To evaluate
      the suitability of the dynamic SDF assay to assess the adverse effects of agents
      that cause genetic damage, fresh semen samples from different donors were exposed
      in vitro to (1) increasing acute doses of ionizing radiation, (2) elevated
      temperature (41  degrees C and 45  degrees C), (3) acidic pH (pH 4) and (4) the
      nitric oxide (NO) donor sodium nitroprusside (SNP). Sperm DNA fragmentation was
      analyzed after an incubation period of chronic (24h), or acute (1h) exposure to
      each treatment followed by incubation at 37  degrees C over a period of 24h. SDF
      was assessed using the sperm chromatin dispersion (SCD) test. Dynamic SDF for
      each treatment was analyzed using Kaplan-Meier survival curves. All agents,
      except for ionizing radiation, accelerated SDF kinetics following chronic
      exposure over a 24h period. Transient exposure to NO and heat but not acidic pH
      increased the basal (T0) level of SDF. Despite the removal of the three
      toxicants, the remaining sperm following acute exposure showed a decrease in
      their expected DNA longevity. It is concluded that the assessment of sperm DNA
      fragmentation dynamics is an effective methodological approach for revealing
      latent damage associated with toxicants that is not initially expressed following
      a single initial observation of SDF.

PMID- 22469501
TI  - Neighbourhood influences on participation in activities among older adults with
      chronic health conditions.
AB  - We examined the relationships between perceptions of neighbourhood
      characteristics and satisfaction with participation in everyday activities among
      248 older adults with chronic health conditions in Hamilton, Ontario, Canada. We
      used a cross-sectional survey to collect data regarding neighbourhood
      characteristics, social support, social network size, and individual
      characteristics. Path analysis showed that fewer neighbourhood problems directly
      predict higher levels of satisfaction with participation. Neighbourhood cohesion
      indirectly predicts participation by predicting social support, which predicts
      participation. Neighbourhood safety indirectly predicts participation by
      predicting increased social cohesion and neighbourhood amenities may influence
      participation similarly. Changes to neighbourhood characteristics have the
      potential to facilitate participation in daily activities for older adults with
      chronic health conditions.

PMID- 22469502
TI  - West Nile virus lineage 2 from blood donor, Greece.

PMID- 22469503
TI  - Early thrombus removal strategies for acute deep venous thrombosis: clinical
      practice guidelines of the Society for Vascular Surgery and the American Venous
      Forum.
AB  - BACKGROUND: The anticoagulant treatment of acute deep venous thrombosis (DVT) has
      been historically directed toward the prevention of recurrent venous
      thromboembolism. However, such treatment imperfectly protects against late
      manifestations of the postthrombotic syndrome. By restoring venous patency and
      preserving valvular function, early thrombus removal strategies can potentially
      decrease postthrombotic morbidity. OBJECTIVE: A committee of experts in venous
      disease was charged by the Society for Vascular Surgery and the American Venous
      Forum to develop evidence-based practice guidelines for early thrombus removal
      strategies, including catheter-directed pharmacologic thrombolysis,
      pharmacomechanical thrombolysis, and surgical thrombectomy. METHODS: Evidence
      based recommendations are based on a systematic review and meta-analysis of the
      relevant literature, supplemented when necessary by less rigorous data.
      Recommendations are made according to the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) methodology, incorporating the strength of the
      recommendation (strong: 1; weak: 2) and an evaluation of the level of the
      evidence (A to C). RESULTS: On the basis of the best evidence currently
      available, we recommend against routine use of the term "proximal venous
      thrombosis" in favor of more precise characterization of thrombi as involving the
      iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the
      use of early thrombus removal strategies in ambulatory patients with good
      functional capacity and a first episode of iliofemoral DVT of <14 days in
      duration (Grade 2C) and strongly recommend their use in patients with limb
      threatening ischemia due to iliofemoral venous outflow obstruction (Grade 1A). We
      suggest pharmacomechanical strategies over catheter-directed pharmacologic
      thrombolysis alone if resources are available and that surgical thrombectomy be
      considered if thrombolytic therapy is contraindicated (Grade 2C). CONCLUSIONS:
      Most data regarding early thrombus removal strategies are of low quality but do
      suggest patient-important benefits with respect to reducing postthrombotic
      morbidity. We anticipate revision of these guidelines as additional evidence
      becomes available.

PMID- 22469504
TI  - Influenza-associated hospitalizations by industry, 2009-10 influenza season,
      United States.
AB  - In response to pandemic (H1N1) 2009, data were collected on work status and
      industry of employment of 3,365 adults hospitalized with laboratory-confirmed
      influenza during the 2009-10 influenza season in the United States. The
      proportion of workers hospitalized for influenza was lower than their proportion
      in the general population, reflecting underlying protective characteristics of
      workers compared with nonworkers. The most commonly represented sectors were
      transportation and warehousing; administrative and support and waste management
      and remediation services; health care; and accommodation and food service.

PMID- 22469505
TI  - Crimean-Congo hemorrhagic fever, Kazakhstan, 2009-2010.
AB  - We evaluated Crimean-Congo hemorrhagic fever (CCHF) surveillance data from
      southern Kazakhstan during 2009-2010 and found both spatial and temporal
      association between reported tick bites and CCHF cases. Public health measures
      should center on preventing tick bites, increasing awareness of CCHF signs and
      symptoms, and adopting hospital infection control practices.

PMID- 22469506
TI  - The genetics of gestational trophoblastic disease: a rare complication of
      pregnancy.
AB  - Gestational choriocarcinoma is usually a rapidly spreading fatal disease, but it
      is curable if diagnosed early and treated. It is a unique malignancy that is a
      partial or complete allograft with a genotype that is not the same as the host
      genotype. It is most often preceded by an abnormal molar pregnancy. The
      surprising and unique androgenetic origin of complete hydatidiform molar
      pregnancies was first revealed by Kajii and Ohama in 1977. We describe the
      current understanding of the morphology, epidemiology and genetics of gestational
      trophoblastic disease that followed the milestone findings by Kajii and Ohama.

PMID- 22469507
TI  - SNP-based arrays complement classic cytogenetics in the detection of chromosomal
      aberrations in Wilms' tumor.
AB  - Wilms' tumors have characteristic chromosomal abnormalities, such as the 11p13
      deletion, in a subset of cases. This is one of the very few reports comparing
      single nucleotide polymorphism (SNP) array analysis with conventional karyotyping
      of Wilms' tumors. A total of 43 frozen tumor samples were analyzed using the
      Affymetrix Cytogenetics Whole-Genome 2.7M array. The findings from the SNP array
      analysis were then compared with those from conventional karyotyping. A
      comparison between SNP array and conventional karyotype findings was possible in
      38 of 43 specimens (88.4%). The SNP array and classic cytogenetic results were
      concordant in 33 of 38 specimens (87%). SNP array analysis was able to support
      the findings of classic cytogenetics. The SNP array detected regions of loss of
      heterozygosity (LOH) in 41 of 43 (95%) specimens. However, it did not detect
      balanced translocations and inversions that were observed by conventional
      cytogenetics. Our results show that the data generated from these platforms are
      complementary. The SNP array also detected additional gains and losses as well as
      regions of LOH with associated disomy, which are likely to represent segmental
      uniparental disomy. The observed discrepancies can be explained by the inherent
      limitations of each technique.

PMID- 22469508
TI  - High frequency of allelic loss at the BRCA1 locus in ovarian cancers:
      clinicopathologic and molecular associations.
AB  - BRCA1 dysfunction may occur by different mechanisms that are rarely evaluated
      concomitantly. We aimed to analyze BRCA1 germline mutations, loss of
      heterozygosity (LOH) and promoter methylation in unselected ovarian carcinomas in
      the context of their clinicopathologic characteristics and other molecular
      changes. BRCA1 mutations were analyzed in 257 carcinomas using single-strand
      conformation polymorphism (SSCP), heteroduplex, and sequencing methods. LOH at
      the BRCA1 locus was screened for in 180 cancers. Methylation analysis was
      performed for 241 tumors using quantitative methylation specific PCR (qMSP).
      BRCA1 alterations, comprising germline mutations, allelic loss, and/or aberrant
      promoter methylation, were found in 77.6% (125/161) of ovarian carcinomas.
      Patients with germline mutations were younger than non-carriers (P < 0.0001).
      Germline mutations and LOH were associated with advanced stages (P=0.009, P <
      0.0001), high tumor grade (P=0.005, P < 0.0001), and TP53 mutations (P=0.003, P <
      0.0001, for mutations and LOH, respectively). LOH was also associated with the
      serous histological type (P=0.004) and PIK3CA amplification (P=0.003). Aberrant
      promoter methylation was associated with LOH (P=0.017) and absence of germline
      mutations (P=0.037). The high frequency of LOH at the BRCA1 locus suggests that
      LOH may be an important mechanism of BRCA1 deficiency in ovarian carcinomas.
      Tumors with various BRCA1 alterations have a similar phenotype of high-grade,
      high-stage carcinomas with frequent TP53 mutations.

PMID- 22469509
TI  - Evolution in a transmissible cancer: a study of the chromosomal changes in devil
      facial tumor (DFT) as it spreads through the wild Tasmanian devil population.
AB  - Tasmanian devils (Sarcophilus harrisii) are the largest extant marsupial
      carnivores. This species, now confined to Tasmania, is endangered from the
      emergence of a transmissible cancer, devil facial tumor disease (DFTD). In the
      present study, we use cytogenetic and molecular techniques to examine the
      stability of devil facial tumor (DFT) cell lines across time and space. This
      article describes disease progression from February 2004 to June 2011. We
      demonstrate evolutionary changes in the disease, which affects devils in
      different sites across Tasmania and over a period of several years, producing
      several chromosomal variants (strains) that are capable of transmission between
      devils. We describe the evolution of DFTs in the field and speculate on the
      possible impacts on the disease, including (1) development of less aggressive
      forms of the disease; (2) development of more aggressive forms of the disease;
      (3) development of forms capable of affecting closely related species of
      dasyurids (e.g., quolls); (4) extinction of the disease as it acquires additional
      deleterious mutations that affect either cell viability or transmissibility; and
      (5) co-evolution of the disease and the host. We also speculate about the future
      of the Tasmanian devil in the wild. We note that although DFTs are regarded as
      unstable by comparison with another much older transmissible cancer, canine
      transmissible venereal tumor (CTVT), the potential for development of less
      aggressive forms of DFTs or for development of resistance in devils is limited by
      devils' small numbers, low genetic diversity, and restricted geographical
      distribution.

PMID- 22469510
TI  - MicroRNA-26a regulates tumorigenic properties of EZH2 in human lung carcinoma
      cells.
AB  - MicroRNAs (miRNAs) are a class of 21-23 nucleotide RNA molecules that play
      critical roles in the regulation of various cancers, including human lung cancer.
      Among them, miR-26a has been identified as a tumor-related regulator in several
      cancers, but its pathophysiologic properties and correlation with the development
      of human lung cancer remain unclear. In this study, it was determined that miR
      26a expression is clearly down-regulated in human lung cancer tissues relative to
      normal tissues. Meanwhile, the overexpression of miR-26a in the A549 human lung
      cancer cell line dramatically inhibited cell proliferation, blocked G1/S phase
      transition, induced apoptosis, and inhibited cell metastasis and invasion in
      vitro. In contrast, a miR-26a inhibitor was used to transfect A549 cells, and the
      inhibition of endogenous miR-26a promoted cell metastasis and invasion. In
      addition, miR-26a expression inhibited the expression of enhancer of zeste
      homolog 2 (EZH2) and transactivated downstream target genes, including disabled
      homolog 2 (Drosophila) interacting protein gene (DAB2IP) and human Runt-related
      transcription factor 3 (RUNX3), which suggests that EZH2 is a potential target of
      miR-26a as previously reported. In conclusion, miR-26a plays an important role as
      an anti-oncogene in the molecular mechanism of human lung cancer and could
      potentially be used for the treatment of lung cancer.

PMID- 22469511
TI  - The first case of Philadelphia chromosome-negative acute promyelocytic leukemia
      following imatinib for chronic myelogenous leukemia.
AB  - In chronic myelogenous leukemia, chromosomal abnormalities in Philadelphia
      negative cells are rare and usually transient, but can infrequently lead to
      myelodysplastic syndrome and/or acute myeloid leukemia. We report an 82-ear-old
      patient with an 11-year history of chronic myelogenous leukemia, in complete
      cytogenetic response, who developed Philadelphia-negative t(15;17)/PMLRARA acute
      promyelocytic leukemia. This isolated case reaffirms several important
      clinicopathologic and biologic aspects of chronic myelogenous leukemia, and sheds
      a unique light on its Philadelphia-negative hematopoiesis. It also underlines the
      importance of continued cytogenetic monitoring of patients in complete
      cytogenetic response for the emergence of new chromosomal abnormalities.

PMID- 22469512
TI  - Monosomy and ring chromosome 13 in a thyroid nodular goiter-do we underestimate
      its relevance in benign thyroid lesions?
AB  - Classical cytogenetic examination of a thyroid nodular goiter revealed the
      existence of two different cytogenetically aberrant cell clones. They were
      characterized by monosomy 13 as the sole abnormality in one clone, and loss of
      one chromosome 13 and a ring chromosome that was found to consist of chromosome
      13 material by fluorescence in situ hybridization in the other clone. We have
      concluded that during the course of karyotypic evolution, the instability of the
      ring chromosome has led to its loss and subsequent monosomy 13. In the
      literature, two cases of partial monosomy 13 have been reported in adenomatous
      goiters, suggesting that this abnormality characterizes a rare but distinct
      subgroup of benign thyroid lesions histologically presenting as adenomatous
      goiters. Possible target genes of these deletions are the retinoblastoma (RB1)
      gene locus and the MIR16-1/15A cluster. Based on similar changes in other tumors,
      it seems reasonable to also analyze a large number of adenomatous goiters for
      submicroscopic deletions of the long arm of chromosome 13.

PMID- 22469513
TI  - Mitochondrial superoxide mediates doxorubicin-induced keratinocyte apoptosis
      through oxidative modification of ERK and Bcl-2 ubiquitination.
AB  - Massive apoptosis of keratinocytes has been implicated in the pathogenesis of
      chemotherapy-induced skin toxicities, but the underlying mechanisms of action are
      not well understood. The present study investigated the apoptotic effect of
      doxorubicin (DOX) on HaCaT keratinocytes and determined the underlying
      mechanisms. Treatment of the cells with DOX induced reactive oxygen species (ROS)
      generation and a concomitant increase in apoptotic cell death through the
      mitochondrial death pathway independent of p53. Electron spin resonance and flow
      cytometry studies showed that superoxide is the primary oxidative species induced
      by DOX and responsible for the death inducing effect. Ectopic expression of
      mitochondrial superoxide scavenging enzyme (MnSOD) or treatment with MnSOD
      mimetic (MnTBAP) inhibited DOX-induced superoxide generation and apoptosis. The
      mechanism by which superoxide mediates the apoptotic effect of DOX was shown to
      involve downregulation of Bcl-2 through ubiquitin-proteasomal degradation.
      Superoxide induces dephosphorylation of Bcl-2 through MAP kinase ERK1/2
      inactivation, which promotes ubiquitination of Bcl-2. We also provide evidence
      for the oxidative modification of ERK1/2 through cysteine sulfenic acid
      formation. These findings indicate a novel pathway for redox regulation of
      apoptosis regulatory proteins, which could be important in the understanding of
      chemotherapy-induced toxicities and development of preventive treatment
      strategies which are currently lacking.

PMID- 22469515
TI  - The effect of radixin knockdown on the expression and efflux function of MRP2 in
      SGC-7901 cells.
AB  - Multidrug resistance-associated protein 2 (MRP2, ABCC2) is the second member of
      the MRP transporter family and functions physiologically as an organic anion
      transporter. Earlier studies have confirmed that radixin, which is a member of
      the ERM (ezrin/radixin/moesin) family, modulates MRP2 localization at the
      canalicular membrane in hepatocytes. The relationship between radixin and MRP2 -
      particularly, the effect of radixin on the expression and function of MRP2 in
      cells or tissues that co-express all three ERM proteins - has not been well
      studied. To examine the role of radixin in the expression and function of MRP2
      and other MRPs, we chose human gastric carcinoma SGC-7901 cells that express all
      three ERM proteins rather than hepatocytes, which predominantly express radixin.
      Radixin stable knockdown SGC-7901 cells, which were constructed by RNAi,
      exhibited no compensatory up-regulation of ezrin or moesin. The mRNA expression
      profiles of MRPs in the radixin knockdown cells were primarily evaluated by RT
      PCR. Real time quantitative RT-PCR and western blot analysis revealed that the
      radixin deficiency caused the mRNA and protein expression levels of MRP2 to be
      reduced by about 50%, respectively. Accordingly, efflux and MTT assays showed
      that the radixin knockdown cells exhibited lower efflux ability with respect to
      calcein but no significant change in cell viability. In conclusion, among the
      MRP1-6 family members, radixin selectively modulates the expression and function
      of MRP2 in a system co-expressing all three ERM proteins.

PMID- 22469514
TI  - The Bacillus subtilis cannibalism toxin SDP collapses the proton motive force and
      induces autolysis.
AB  - Bacillus subtilis SDP is a peptide toxin that kills cells outside the biofilm to
      support continued growth. We show that purified SDP acts like endogenously
      produced SDP; it delays sporulation, and the SdpI immunity protein confers SDP
      resistance. SDP kills a variety of Gram-positive bacteria in the phylum
      Firmicutes, as well as Escherichia coli with a compromised outer membrane,
      suggesting it participates in defence of the B. subtilis biofilm against Gram
      positive bacteria as well as cannibalism. Fluorescence microscopy reveals that
      the effect of SDP on cells differs from that of nisin, nigericin, valinomycin and
      vancomycin-KCl, but resembles that of CCCP, DNP and azide. Indeed, SDP rapidly
      collapses the PMF as measured by fluorometry and flow cytometry, which triggers
      the slower process of autolysis. This secondary consequence of SDP treatment is
      not required for cell death since the autolysin-defective lytC, lytD, lytE, lytF
      strain fails to be lysed but is nevertheless killed by SDP. Collapsing the PMF is
      an ideal mechanism for a toxin involved in cannibalism and biofilm defence, since
      this would incapacitate neighbouring cells by inhibiting motility and secretion
      of proteins and toxins. It would also induce autolysis in many Gram-positive
      species, thereby releasing nutrients that promote biofilm growth.

PMID- 22469516
TI  - Berberine activates Nrf2 nuclear translocation and protects against oxidative
      damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor
      neuron-like cells.
AB  - Berberine (BBR) is a well-known anti-diabetic herbal medicine in Asia due to its
      beneficial effects on insulin sensitivity, glucose metabolism and glycolysis.
      Here, we identified the critical role of phosphatidylinositol 3-kinase (PI3K)/Akt
      involved BBR cellular defense mechanisms and first revealed the novel effect of
      BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2)/heme
      oxygenase (HO)-1 induction in NSC34 motor neuron-like cells. BBR (0.1-10 nM) led
      to increasing insulin receptor expression, Akt phosphorylation and enhanced
      oxidant-sensitive Nrf2/HO-1 induction, which were blocked by a PI3K inhibitor,
      LY294002. In H(2)O(2)-treated cells, BBR significantly attenuated ROS production
      and increased cell viability, antioxidant defense (GSH and SOD) and oxidant
      sensitive proteins (HO-1 and Nrf2), which also were blocked by LY294002.
      Furthermore, BBR improved mitochondrial function by increasing mitochondrial
      membrane potential and decreasing the oxygen consumption rate. BBR-induced anti
      apoptotic function was demonstrated by increasing anti-apoptotic protein Bcl-2
      and survival of motor neuron protein (SMN) and by decreasing apoptotic proteins
      (cytochrome c, Bax and caspase). These results suggest that BBR, which is active
      at nanomolar concentration, is a potential neuroprotective agent via PI3K/Akt
      dependent cytoprotective and antioxidant pathways.

PMID- 22469517
TI  - Guiding differentiation of stem cells in vivo by tetracycline-controlled
      expression of key transcription factors.
AB  - Transplantation of stem or progenitor cells is an attractive strategy for cell
      replacement therapy. However, poor long-term survival and insufficiently
      reproducible differentiation to functionally appropriate cells in vivo still
      present major obstacles for translation of this methodology  to clinical
      applications. Numerous experimental studies have revealed that the expression of
      just a few transcription factors can be sufficient to drive stem cell
      differentiation toward a specific cell type, to transdifferentiate cells from one
      fate to another, or to dedifferentiate mature  cells to pluripotent
      stem/progenitor cells (iPSCs). We thus propose here to apply the strategy of
      expressing the relevant key transcription factors to guide the differentiation of
      transplanted cells to the desired cell fate in vivo. To achieve this requires
      tools allowing us to control the  expression of these genes in the transplant.
      Here, we describe drug-inducible systems that allow us to sequentially and timely
      activate gene expression from the outside, with a particular emphasis on the Tet
      system, which has been widely and successfully used in stem cells. These
      regulatory  systems offer a tool for strictly limiting gene expression to the
      respective optimal stage after transplantation. This approach will direct the
      differentiation of the immature stem/progenitor cells in vivo to the desired cell
      type.

PMID- 22469518
TI  - beta-Glucan treatment prevents progressive burn ischaemia in the zone of stasis
      and improves burn healing: an experimental study in rats.
AB  - Saving the zone of stasis is one of the major goals of burn specialists.
      Increasing the tissue tolerance to ischaemia and inhibiting inflammation have
      been proposed to enable salvage of this zone. After a burn, excessive
      inflammation, including increased vascular permeability, local tissue oedema and
      neutrophil activation, causes local tissue damage by triggering vascular
      thrombosis and blocking capillaries, resulting in tissue ischaemia and necrosis.
      Oxygen radicals also contribute to tissue damage after a burn. However,
      macrophages play a pivotal role in the response to burn. We studied beta-glucan
      because of its many positive systemic effects that are beneficial to burn
      healing, including immunomodulatory effects, antioxidant effects (free-radical
      scavenging activity) and effects associated with the reduction of the
      inflammatory response. There were four test groups in this study with eight rats
      in each group. Group 1 was the control group, group 2 was administered a local
      pomade (bacitracin+neomycin sulphate), group 3 received beta-glucan (50 mg kg(
      1), orally) + the local pomade and group 4 received beta-glucan. Burns were
      created using a brass comb model. Macroscopic, histopathological and statistical
      assessments were performed. Samples were harvested on the 3rd, 7th and 21 days
      for analysis. The neutrophilic infiltration into the zone of stasis was analysed
      on day 3. Macrophage infiltration, fibroblast proliferation, angiogenesis and re
      epithelialisation ratios in the zone of stasis were analysed on days 7 and 21.
      The beta-glucan groups (groups 3 and 4) exhibited lower neutrophil counts on the
      3rd day, and macrophage infiltration, fibroblast proliferation, angiogenesis and
      re-epithelialisation were very high in these groups on the 7th day. In
      particular, re-epithelialisation on the 21st day was significantly better in the
      beta-glucan groups. This study demonstrated that beta-glucan may prevent
      neutrophil-dependent tissue damage and burn-induced oxidative injury through its
      anti-inflammatory and antioxidant properties. We speculate that the inhibition of
      neutrophil activation preserves vascular patency by preventing capillary
      blockage. beta-Glucan is also a powerful macrophage stimulator, and is therefore
      very effective in saving the zone of stasis.

PMID- 22469519
TI  - Multidisciplinary and evidence-based method for prioritizing diseases of food
      producing animals and zoonoses.
AB  - To prioritize 100 animal diseases and zoonoses in Europe, we used a multicriteria
      decision-making procedure based on opinions of experts and evidence-based data.
      Forty international experts performed intracategory and intercategory weighting
      of 57 prioritization criteria. Two methods (deterministic with mean of each
      weight and probabilistic with distribution functions of weights by using Monte
      Carlo simulation) were used to calculate a score for each disease. Consecutive
      ranking was established. Few differences were observed between each method.
      Compared with previous prioritization methods, our procedure is evidence based,
      includes a range of fields and criteria while considering uncertainty, and will
      be useful for analyzing diseases that affect public health.

PMID- 22469520
TI  - Intraventricularly injected Olig2-NSCs attenuate established relapsing-remitting
      EAE in mice.
AB  - In multiple sclerosis (MS), a chronic inflammatory relapsing demyelinating
      disease, failure to control or repair damage leads to progressive neurological
      dysfunction and neurodegeneration. Implantation of neural stem cells (NSCs) has
      been shown to promote repair and functional recovery  in the acute experimental
      autoimmune encephalomyelitis (EAE) animal model for MS; the major therapeutic
      mechanism of these NSCs appeared to be immune regulation. In the present study,
      we examined the efficacy of intraventricularly injected NSCs in chronic relapsing
      experimental autoimmune  encephalomyelitis (CREAE), the animal disease model that
      is widely accepted to mimic most closely recurrent inflammatory demyelination
      lesions as observed in relapsing-remitting MS. In addition, we assessed whether
      priming these NSCs to become oligodendrocyte precursor cells (OPCs)  by transient
      overexpression of Olig2 would further promote functional recovery, for example,
      by contributing to actual remyelination. Upon injection at the onset of the acute
      phase or the relapse phase of CREAE, NSCs as well as Olig2-NSCs directly migrated
      toward active lesions in the spinal  cord as visualized by in vivo
      bioluminescence and biofluorescence imaging, and once in the spinal cord, the
      majority of Olig2-NSCs, in contrast to NSCs, differentiated into OPCs. The
      survival of Olig2-NSCs was significantly higher than that of injected control
      NSCs, which remained undifferentiated.  Nevertheless, both Olig2-NSCs and NSC
      significantly reduced the clinical signs of acute and relapsing disease and, in
      case of Olig2-NSCs, even completely abrogated relapsing disease when administered
      early after onset of acute disease. We provide the first evidence that NSCs and
      in particular  NSC-derived OPCs (Olig2-NSCs) ameliorate established chronic
      relapsing EAE in mice. Our experimental data in established neurological disease
      in mice indicate that such therapy may be effective in relapsing-remitting MS
      preventing chronic progressive disease.

PMID- 22469521
TI  - Multiple myeloma in octogenarians: clinical features and outcome in the novel
      agent era.
AB  - BACKGROUND: Multiple myeloma (MM) affects mainly elderly persons and because the
      population of octogenarians increases, it is common to treat patients >= 80 years
      of age. These patients are often not included in clinical trials; thus, there is
      limited data on their characteristics and treatment outcome. PATIENTS AND
      METHODS: We retrospectively analyzed 682 consecutive, unselected patients with
      newly diagnosed symptomatic myeloma who started treatment between January 1, 2003
      and December 31, 2010. RESULTS: We identified 155 (23%) patients >= 80 years of
      age. Compared to patients <80 years, octogenarians had poorer performance status
      (P < 0.001), anemia (P = 0.006), low serum albumin (P = 0.001), and advanced ISS
      (P < 0.001). The median survival of patients >= 80 years was 22 months, and 14%
      died within 2 months from therapy initiation. The median survival of patients >=
      80 years who received upfront novel agents was 26 vs. 17 months for those who did
      not. ECOG performance status <= 1 and frontline use of novel agents were
      independently associated with better survival. Response to first-line therapy was
      associated with improved survival (29 vs. 16 months, P = 0.017). CONCLUSIONS:
      Patients >= 80 years of age present with features of advanced myeloma and
      impaired performance status. The addition of novel agents may improve their
      outcome, but careful assessment and prospective clinical trials targeting the
      population of elderly patients are needed.

PMID- 22469522
TI  - The diverse roles and clinical relevance of PARPs in DNA damage repair: current
      state of the art.
AB  - Poly(ADP-ribose) polymerase (PARP) catalyzed poly(ADP-ribosyl)ation is one of the
      earliest post-translational modification of proteins detectable at sites of DNA
      strand interruptions. The considerable recent progress in the science of PARP in
      the last decade and the discovery of a PARP superfamily (17 members) has
      introduced this modification as a key mechanism regulating a wide variety of
      cellular processes including among others transcription, regulation of chromatin
      dynamics, telomere homeostasis, differentiation and cell death. However, the most
      extensive studied and probably the best characterized role is in DNA repair where
      it plays pivotal roles in the processing and resolution of the damaged DNA.
      Although much of the focus has been on PARP1 in DNA repair, recent advances
      highlight the emergence of other DNA-dependent PARPs (i.e. PARP2, PARP3 and
      possibly Tankyrase) in this process. Here we will summarize the recent insights
      into the molecular functions of these PARPs in different DNA repair pathways in
      which they emerge as specific actors. Furthermore, the DNA repair functions of
      PARP1 have stimulated another area of intense research in the field with the
      development of potent and selective PARP1 inhibitors to promote genome
      instability and cell death in tumor cells. Their current use in clinical trials
      have demonstrated potentiation of antitumoral drugs and cytotoxicity in repair
      deficient tumor cells.

PMID- 22469523
TI  - Deep brain stimulation for obsessive-compulsive disorder: subthalamic nucleus
      target.
AB  - Because of its reversibility and adaptability, deep brain stimulation (DBS) has
      recently gained interest in psychiatric disorders, such as obsessive-compulsive
      disorders (OCD) and depression. In OCD, DBS is now an alternative procedure to
      lesions of fascicles such as the anterior capsule, which links the orbitofrontal
      cortex, the cingulum, and the thalamus, and has been applied to new target such
      as the nucleus accumbens, with promising results. However, a recent interest has
      been developed toward the subthalamic nucleus (STN), a key structure of the basal
      ganglia that connects the motor, limbic, and associative systems. It is known
      from patients with Parkinson disease that STN-DBS can have significant effects on
      mood and cognition. Those transient effects are usually seen as "side effects" in
      Parkinson disease, but are clues to the underappreciated role that STN plays in
      the limbic circuitry, a role whose precise details are as yet unknown and under
      active investigation. We present the rationale supporting the use of nonmotor STN
      as a therapeutic target to treat OCD. In particular, we discuss the recent
      experience and preliminary results of our group after 6 months of nonmotor STN
      DBS in patients with severe OCD. 

PMID- 22469524
TI  - Seizure control for patients undergoing meningioma surgery.
AB  - OBJECTIVE: Seizures are common among patients with meningiomas and are a
      significant cause of morbidity and poor quality of life. The factors associated
      with the onset of seizures as well as factors associated with seizure control
      remains poorly understood. METHODS: Adult patients who underwent primary
      resection of a supratentorial World Health Organization grade I meningioma at a
      single institution between 1996 and 2006 were retrospectively reviewed.
      Multivariate logistical regression analyses were used to identify associations
      with preoperative seizures, and multivariate proportional hazards regression
      analyses were used to identify associations with prolonged seizure control after
      surgical resection. RESULTS: Of the 626 patients in this series, 84 (13%)
      presented with seizures. The factors independently associated with preoperative
      seizures were Karnofsky performance score <= 80 (P< 0.0001), absence of headaches
      (P = 0.0006), and vasogenic edema (P = 0.007). At 48 months postoperatively, 90%
      were Engel class I, 3% were class II, 0 were class III, and 7% were class IV. The
      factors independently associated with decreased seizure control after surgical
      resection were uncontrolled preoperative seizures (P = 0.04), parasagittal tumors
      (P = 0.03), and tumors along the sphenoid wing (P = 0.05). The association
      between seizure recurrence and tumor recurrence trended toward but did not
      achieve statistical significance (P = 0.11). CONCLUSIONS: With the widespread
      availability of various neuroimaging modalities, there will be increased
      detection of intracranial meningiomas. The identification and consideration of
      factors associated with seizure onset and prolonged seizure control may help
      guide treatment strategies aimed at improving the quality of life for patients
      with meningiomas.

PMID- 22469525
TI  - Worldwide survey on the use of navigation in spine surgery.
AB  - OBJECTIVE: Computer-assisted surgery (CAS) can improve the accuracy of screw
      placement and decrease radiation exposure, yet this is not widely accepted among
      spine surgeons. The current viewpoint of spine surgeons on navigation in their
      everyday practice is an important issue that has not been studied. A survey-based
      study assessed opinions on CAS to describe the current global attitudes of
      surgeons on the use of navigation in spine surgery. METHODS: A 12-item
      questionnaire focusing on the number and type of surgical cases, the type of
      equipment available, and general opinions toward CAS was distributed to 3348
      AOSpine surgeons (a specialty group within the AO [Arbeitsgemeinschaft fur
      Osteosynthesefragen] Foundation). Latent class analysis was used to investigate
      the existence of specific groups based on the respondent opinion profiles.
      RESULTS: A response rate of 20% was recorded. Despite a widespread distribution
      of navigation systems in North America and Europe, only 11% of surgeons use it
      routinely. High-volume procedure surgeons, neurological surgeons, and surgeons
      with a busy minimal invasive surgery practice are more likely to use CAS.
      "Routine users" consider the accuracy, potential of facilitating complex surgery,
      and reduction in radiation exposure as the main advantages. The lack of
      equipment, inadequate training, and high costs are the main reasons that
      "nonusers" do not use CAS. CONCLUSIONS: Spine surgeons acknowledge the value of
      CAS, yet current systems do not meet their expectations in terms of ease of use
      and integration into the surgical work flow. To increase its use, CAS has to
      become more cost efficient and scientific data are needed to clarify its
      potential benefits.

PMID- 22469526
TI  - Atlantoaxial fusion with screw-rod constructs: meta-analysis and review of
      literature.
AB  - OBJECTIVE: To review published series describing C1-2 posterior instrumented
      fusions and summarize clinical and radiographic outcomes of patients treated with
      screw-rod constructs (SRC). METHODS: Online databases were searched for English
      language articles published between 1991 and April 2011 describing posterior
      atlantoaxial instrumentation with C1-2 SRC. There were 24 studies including 1073
      patients treated with SRC that fulfilled inclusion criteria. Meta-analysis
      techniques were used to compare outcomes. RESULTS: All studies provided class III
      evidence. The 30-day perioperative mortality rate was 0.6%, and neurologic injury
      occurred in two patients with vertebral artery injury (VAI) from screw
      malpositions (0.2%). The incidence of clinically significant screw malpositions
      was 2.4% (confidence interval [CI], 1.1%-4.1%), the incidence of VAI was 2.0%
      (CI, 1.1%-3.4%), and the rate of fusion with the SRC technique was 97.5% (CI,
      95.9%-98.5%). CONCLUSIONS: SRC is a safe and effective treatment option for C1-2
      instability. The low but nonzero incidence of screw malposition and VAI
      emphasizes the necessity of having a thorough knowledge of atlantoaxial anatomy
      for successful insertion of screws.

PMID- 22469528
TI  - Local pain, global prescriptions? Using scale to analyse the globalisation of the
      HIV/AIDS response.

PMID- 22469527
TI  - Atlantoaxial fusion with transarticular screws: meta-analysis and review of the
      literature.
AB  - OBJECTIVE: To review published series describing C1-2 posterior instrumented
      fusions and summarize clinical and radiographic outcomes of patients treated with
      transarticular screw (TAS) fixation. METHODS: Online databases were searched for
      English-language articles published between 1986 and April 2011 describing
      posterior atlantoaxial instrumentation with C1-2 TAS fixation. There were 45
      studies including 2073 patients treated with TAS that fulfilled inclusion
      criteria. Meta-analysis techniques were used to calculate outcomes. RESULTS: All
      studies provided class III evidence. The 30-day perioperative mortality rate was
      0.8%, and the incidence of neurologic injury was 0.2%. The incidence of
      clinically significant malpositioned screws was 7.1% (confidence interval [CI],
      5.7%-8.8%), the incidence of vertebral artery injury was 3.1% (CI, 2.3%-4.3%),
      and the rate of fusion with the TAS technique was 94.6% (CI, 92.6%-96.1%).
      CONCLUSIONS: TAS fixation is a safe and effective treatment option for C1-2
      instability with high rates of fusion (approximately 95%). Screw malposition and
      vertebral artery injury occurred in approximately 5% of patients. The successful
      insertion of TAS requires a thorough knowledge of atlantoaxial anatomy.

PMID- 22469529
TI  - The global governance of success in HIV/AIDS policy: emergency action, everyday
      lives and Sen's capabilities.
AB  - The article explores how the social construction of 'success' by program funders
      foregrounds the role of biomedicine in advancing health, with no attention to the
      wider social contexts that make it possible for poor people to use this medicine
      to advance their health. The article considers the impact of the governance of
      the disease in Burundi. The case study highlights the disjuncture between the
      assumed ideal governance of the disease and people's needs to obtain healthy
      lives.

PMID- 22469530
TI  - Making sense of 'gender': from global HIV/AIDS strategy to the local Cambodian
      ground.
AB  - Interventions aiming to promote gender equality are a common feature of global
      HIV/AIDS policies. To develop effective interventions, it is important to
      understand how globally established concepts (e.g. 'gender') are (re)interpreted
      and legitimated locally. This paper examines what happens when the concept of
      'gender' hits the local ground in the context of an internationally funded
      HIV/AIDS intervention in Cambodia. Interviews with participants reveal that
      'gender' is itself understood to mean equal rights. Some elements of this concept
      are rejected as inapplicable in Khmer society, while others are hybridised with
      existing knowledges. The analysis demonstrates how relational, symbolic and
      material dimensions of the place into which HIV/AIDS programmes intervene shape
      not only what 'sense' participants make of new knowledge, but also their capacity
      to use it. Further, the paper argues that to achieve the desired health-enhancing
      outcomes, international health organisations must avoid essentialising local
      spaces as static and 'traditional'; rather, they must attend to and build on the
      ambiguities of existing knowledges and the changing dynamics of the places they
      enter.

PMID- 22469531
TI  - From brothel to boardroom: prospects for community leadership of HIV
      interventions in the context of global funding practices.
AB  - The empowerment of marginalised communities to lead local responses to HIV/AIDS
      is a key strategy of funding agencies' globalised HIV/AIDS policies, given
      evidence that disempowerment is a root source of vulnerability to HIV. We report
      on two multi-level ethnographies at the interface between HIV prevention projects
      for sex workers in India and their funding environment, examining the extent to
      which the funding environment itself promotes or undermines sex worker
      empowerment. We show how the 'new managerialism' characteristic of the funding
      system undermines sex worker leadership of HIV interventions. By requiring local
      projects to conform to global management standards, funding agencies risk
      undermining the very localism and empowerment that their intervention policies
      espouse.

PMID- 22469532
TI  - AIDS NGOS and corruption in Nigeria.
AB  - Using two ethnographic case studies, the intersecting dynamics of inequality,
      morality, and corruption are examined as they play out in Nigerian AIDS NGOs. To
      the Nigerian public, local AIDS organizations are widely seen as conduits for
      corruption. But local opinions of particular NGOs and their leaders turn less on
      whether donor resources were misused and more on the ways that people who
      accumulate the benefits of corruption use them socially. Nevertheless, discontent
      swirls about corruption in general, a fact that suggests a gradual change in
      people's understandings of the processes that produce inequality in Nigeria.

PMID- 22469533
TI  - Drug partnerships and global practices.
AB  - Tuberculosis poses one of the biggest threats to individuals living with HIV in
      most low-income regions of the world, and the increase of multi-drug resistant
      tuberculosis (MDR-TB) in South Africa, Eastern Europe, and elsewhere makes this
      threat that much more critical. Despite the extent of the problem, new drugs for
      tuberculosis have not been developed for over four decades, largely because
      tuberculosis occurs primarily among the poor in low-income regions and the market
      for tuberculosis drugs is not lucrative enough to warrant time and resource
      commitments by pharmaceutical companies. In the wake of sustained global
      criticism of pharmaceutical-state practices, however, new partnerships for drug
      development (PDPs) are forming to address critical shortages of drugs for
      diseases like tuberculosis that have been termed 'neglected' precisely because
      they have not seen new treatments for so long. This paper examines some of these
      partnerships, tracing some of the dynamic developments as well as challenges in
      forging alternative pathways to new drug and vaccine production.

PMID- 22469534
TI  - Pleasant physical exercise program for prevention of cognitive decline in
      community-dwelling elderly with subjective memory complaints.
AB  - AIM: Japan is one of the most rapidly aging societies in the world. Measures to
      prevent dementia are urgently required in Japan, although such strategies have
      not yet been established. This study investigated the effectiveness of a pleasant
      physical exercise intervention on the prevention of cognitive decline in
      community-dwelling elderly participants with subjective memory complaints. In
      this intervention, a pleasant atmosphere was emphasized to enhance the
      participants' motivation. METHOD: We administered a 12-week intervention program
      consisting of pleasant physical exercise. This program for the prevention of
      cognitive decline was carried out as a service of Maebashi city. The service
      targeted elderly residents aged 65 years and older who had subjective memory
      complaints. After a control period of 12 weeks, 42 participants, aged between 65
      86 years, received intervention once a week at community centers. Participants
      carried out group exercise, and were encouraged to perform home exercise and
      walking during the intervention period. The program was carried out by co-medical
      professional staff, with the help of senior citizen volunteers. RESULTS: A total
      of 30 participants were included in the analysis. There was significant
      improvement on the Wechsler digit symbol substitution test (P = 0.01).
      CONCLUSION: Participants with subjective memory complaints who continued the
      pleasant physical exercise programs for 12 weeks showed improvement in some
      aspects of cognitive function. Participation of senior citizen volunteers enabled
      smooth implementation of the program, and alleviated the burden on the
      professional staff. The pleasant physical exercise intervention described in the
      present study could be regarded as a community-led intervention to prevent
      cognitive decline.

PMID- 22469535
TI  - Identification of risk factors for chronic Q fever, the Netherlands.
AB  - Since 2007, the Netherlands has experienced a large Q fever outbreak. To identify
      and quantify risk factors for development of chronic Q fever after Coxiella
      burnetii infection, we performed a case-control study. Comorbidity,
      cardiovascular risk factors, medications, and demographic characteristics from
      105 patients with proven (n = 44), probable (n = 28), or possible (n = 33)
      chronic Q fever were compared with 201 patients who had acute Q fever in 2009 but
      in whom chronic Q fever did not develop (controls). Independent risk factors for
      development of proven chronic Q fever were valvular surgery, vascular prosthesis,
      aneurysm, renal insufficiency, and older age.

PMID- 22469536
TI  - Vector blood meals and Chagas disease transmission potential, United States.
AB  - A high proportion of triatomine insects, vectors for Trypanosoma cruzi
      trypanosomes, collected in Arizona and California and examined using a novel
      assay had fed on humans. Other triatomine insects were positive for T. cruzi
      parasite infection, which indicates that the potential exists for vector
      transmission of Chagas disease in the United States.

PMID- 22469537
TI  - Triacylglycerols composition, oxidation and oxidation compounds in camellia oil
      using liquid chromatography-mass spectrometry.
AB  - Camellia seed oil is one of most important edible oil, rich in oleic acid and
      contains many natural antioxidants with various biological activities. During
      preparation of foods or storage camellia oil oxidizes by the auto-oxidation and
      produce oxidized compounds. Traditional analytical techniques like FFA, POV are
      used for the determination of oxidation and adulteration of oils and fats. These
      methods were rarely able to detect the oxidized compounds produced and extent of
      oxidation. This paper presents the uses of liquid chromatography coupled to
      electrospray ionization mass spectrometry (HPLC-ESI-MS) for the analysis of
      triacylglycerols (TAGs) composition and evaluation of auto-oxidation and
      oxidation products of camellia seed oil. The camellia oil was auto-oxidized for
      12 months at room temperature. The TAGs were identified from their
      characteristics fragmentations such as protonated molecular ion, ammonium and
      sodium adducts, diacylglycerols, epoxy-diacylglycerols fragments and mono
      acylglycerol fragments in ESI-MS mass spectra. HPLC-ESI-MS data revealed the
      separation and identification of 15 TAGs. The major TAGs separated and identified
      in camellia seed oil were POO, OOO, OLO, PLO/POL, OLL, SOO, ALO and OLLn. The
      auto-oxidation studies revealed a total loss of LnLLn, LnOLn, LLLn and OLLn
      amounting about 13.5% total oxidation. The auto-oxidation products were epoxy
      hydroperoxides, epoxy epidioxides, and mono-epoxides. It was observed that these
      were characteristic compounds produced in high oleic oils.

PMID- 22469538
TI  - Acyclovir: comprehensive profile.

PMID- 22469539
TI  - Ceftriaxone sodium: comprehensive profile.

PMID- 22469540
TI  - Ipratropium bromide: physical properties.

PMID- 22469541
TI  - Ipratropium bromide: methods of chemical and biochemical synthesis.

PMID- 22469542
TI  - Ipratropium bromide: analytical methods.

PMID- 22469543
TI  - Ipratropium bromide: drug metabolism and pharmacokinetics.

PMID- 22469544
TI  - Ornidazole: comprehensive profile.

PMID- 22469545
TI  - Sertraline (L)-lactate: comprehensive profile.

PMID- 22469546
TI  - Propylparaben: physical characteristics.

PMID- 22469547
TI  - X-ray diffraction of pharmaceutical materials.

PMID- 22469548
TI  - Cumulative index.

PMID- 22469550
TI  - Affiliations of editor and contributors.

PMID- 22469551
TI  - Relationship of creatinine and nutrition with arsenic metabolism.

PMID- 22469552
TI  - [PAIR-gynaecology: multi/interdisciplinary for gynecologic cancer research.
      Problems needed to be resolved].
AB  - Each year, 13,000 newly gynecologic cancers are diagnosed in France. Gynecologic
      cancers were specifically heterogeneous (localisations, histologic subgroups, age
      class, etc). This work was delineated for a national call dedicated to
      gynecologic cancers. This review reports the major needs in terms of scientific
      research dedicated to gynecologic cancers in the biologic, epidemiology, human
      and sociologic fields. For example, medico-economic strategies adapted to
      ethnosociologic context, specifically for cervix cancer, took important part of
      the epidemiologic research. Impact of gynecologic cancer in terms of symptoms and
      late effects, quality of life after treatments and fertility needs to be
      specifically explored. For fundamental research, molecular characterisation,
      biologic markers, impact of immunology and genetics represent the major part of
      the field need to be explored. Finally, therapeutic and diagnosis innovations,
      optimization of treatments strategies and development of predictive models in
      order to perform individual prediction taking into account several risk factors
      (clinical and molecular) to offer help in management of gynecologic cancers are
      required.

PMID- 22469553
TI  - Unbiased entropy estimates in stress: a parameter study.
AB  - This study proposes a method for obtaining a stable working point that enables
      the unbiased estimates of the approximate entropy and the sample entropy. Pattern
      length, normalized threshold, time delay and tines series length are levels of
      freedom that are considered. Pulse interval signals used for the experiment are
      recorded from laboratory animals with different likelihood of developing
      cardiovascular disease--normal and borderline hypertensive rats--exposed to the
      acute and to the chronic stress. It is shown that the threshold level is the
      major source of the instability, and that the generally accepted and widely used
      methods for a threshold choice may lead to an incorrect psychological
      interpretation. A method for the threshold level correction is proposed.

PMID- 22469554
TI  - The co-drug of conjugated hydroquinone and azelaic acid to enhance topical skin
      targeting and decrease penetration through the skin.
AB  - A co-drug of hydroquinone (HQ) and azelaic acid (AA), bis(4
      hydroxyphenyl)nonanedioate (BHN), was synthesized and investigated as a topical
      prodrug with the aim of improving the dermal delivery of the parent drugs.
      Physicochemical parameters were ascertained, and the enzymatic hydrolysis was
      examined. Skin permeation of HQ, AA, and BHN was studied by determining the skin
      deposition and flux across nude mouse skin under equivalent doses with the same
      thermodynamic activity. The partition coefficient (log P) of the co-drug
      increased by up to 5.0 with HQ and AA conjugation, which had respective log P
      values of 0.5 and 1.4. In the skin absorption experiment, BHN in ethanol/pH 7
      buffer resulted in a 2-fold enhancement of skin deposition compared to both HQ
      and AA. With permeation using polyethylene glycol 400/pH 7 buffer as the vehicle,
      the co-drug, respectively, exhibited 8.1- and 1.4-fold enhancements of skin
      uptake compared to HQ and AA alone. The transdermal flux from BHN was negligible
      compared to those with HQ and AA treatments. The results of a preliminary safety
      evaluation showed no signs of stratum corneum disruption or erythema by BHN
      application within 24h. The co-drug approach provides a viable option for the
      treatment of skin hyperpigmentation of HQ and AA.

PMID- 22469555
TI  - Effect of atomic impurities on the helical surface states of the topological
      insulator Bi2Te3.
AB  - The effect of atomic impurities including N, O, Na, Ti and Co on the surface
      states of the topological insulator (TI) Bi(2)Te(3) is studied using
      pseudopotential first principles methods. The robustness of the TI surface states
      is particularly investigated against magnetic and non-magnetic atomic adsorption
      by calculating the electronic band structure, charge transfer, and magnetic
      moments. Interestingly, it is found that a non-magnetic nitrogen atom has
      produced a residual magnetic moment and opens a gap in the surface states whereas
      Na and O atoms preserve the Dirac-like dispersion. The charge transfer from the
      adatoms produces an electric dipole field that causes Rashba splitting in the
      surface bands. For atomic impurities with 3d orbitals (Ti and Co), the TI surface
      states are destroyed and two spin-resolved resonance peaks are developed near the
      Fermi level in the DOS.

PMID- 22469556
TI  - Survey of antibiotic prophylaxis for implantable cardiac electronic device (ICED)
      insertion in England.

PMID- 22469557
TI  - Interventions for the treatment of atrial fibrillation: a systematic literature
      review and meta-analysis.
AB  - BACKGROUND: To perform a systematic review/meta-analysis evaluating the efficacy
      and safety of anti-arrhythmic drugs (AADs) in the treatment of atrial
      fibrillation (AF). METHODS: Database searches (accessed April 2009) were
      conducted to identify randomised controlled trials (RCTs). Comparators of
      interest included all AADs, rate/rhythm strategies or catheter ablation in
      comparison with AADs. Primary AADs of interest were restricted to Class IC
      (flecainide and propafenone) and Class III (amiodarone, dofetilide, dronedarone
      and sotalol). Data were analysed on an intention-to-treat basis and meta-analysis
      performed using the Peto odds ratio (OR)/fixed-effect model. RESULTS: 113
      publications met inclusion criteria. Of these, 74 publications considered an AAD
      of primary interest. The odds of AF recurrence were generally significantly lower
      with all active treatments versus non-active control. Dronedarone was the only
      AAD to show a (non-significant) trend towards reducing the odds of mortality with
      a narrow CI (OR 0.85 [0.66, 1.09]). Withdrawals due to adverse events (AEs),
      incidence of serious adverse events (SAEs) and treatment discontinuation were
      increased following active treatment compared with control, with few significant
      differences reported between active treatments. Data for other morbidity outcomes
      such as cardiovascular mortality, hospitalizations or persistence/compliance and
      health-related quality of life (HRQoL) were limited and meta-analyses were not
      possible for these outcomes. CONCLUSION: The current meta-analysis confirms the
      efficacy of AADs in preventing AF recurrence, although their use is associated
      with a greater incidence of AEs and treatment discontinuation. Further RCTs are
      required to establish the benefit of AADs in the management of both morbidity
      outcomes and HRQoL.

PMID- 22469558
TI  - Cancer stem cells: in the line of fire.
AB  - Most tumours appear to contain a sub-population(s) of self-renewing and expanding
      stem cells known as cancer stem cells (CSCs). The CSC model proposes that CSCs
      are at the apex of a hierarchically organized cell population, somewhat akin to
      normal tissue organization. Selection pressures may also facilitate the
      stochastic clonal expansion of sub-sets of cancer cells that may co-exist with
      CSCs and their progeny, moreover the trait of stemness may be more fluid than
      hitherto expected, and cells may switch between the stem and non-stem cell state.
      A large body of evidence points to the fact that CSCs are particularly resistant
      to radiotherapy and chemotherapy. In this review we discuss the basis of such
      resistance that highlights the roles of ABC transporters, aldehyde dehydrogenase
      (ALDH) activity, intracellular signalling pathways, the DNA damage response,
      hypoxia and proliferative quiescence as being significant determinants. In the
      light of such observations, we outline strategies for the successful eradication
      of CSCs, including targeting the self-renewal controlling pathways (Wnt, Notch
      and Hedgehog), ALDH activity and ABC transporters, blocking epithelial
      mesenchymal transition (EMT), differentiation therapy and niche targeting.

PMID- 22469559
TI  - Health-related quality of life in elderly, newly diagnosed multiple myeloma
      patients treated with VMP vs. MP: results from the VISTA trial.
AB  - OBJECTIVES: The phase 3 VISTA study (ClinicalTrials.gov NCT00111319) in
      transplant-ineligible myeloma patients demonstrated superior efficacy with
      bortezomib-melphalan-prednisone (VMP; nine 6-wk cycles) vs. melphalan-prednisone
      (MP) but also increased toxicity. Health-related quality of life (HRQoL;
      exploratory endpoint) was evaluated using the European Organization for Research
      and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). The
      phase 3 VISTA study (ClinicalTrials.gov NCT00111319) in transplant-ineligible
      myeloma patients demonstrated superior efficacy with bortezomib-melphalan
      prednisone (VMP; nine 6-wk cycles) vs. melphalan-prednisone (MP) but also
      increased toxicity. Health-related quality of life (HRQoL; exploratory endpoint)
      was evaluated using the European Organization for Research and Treatment of
      Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). METHODS: EORTC QLQ-C30
      was administered at screening, on day 1 of each cycle, at the end-of-treatment
      visit, and every 8 wk until progression. EORTC QLQ-C30 scores were evaluated
      among patients with a valid baseline and at least one post-baseline HRQoL
      assessment. RESULTS: At baseline, domain scores were similar between arms. By
      cycle 4, mean differences were clinically meaningful for most domains, indicating
      poorer health status with VMP. From cycle 5 onwards, improvements relative to
      baseline/MP were observed for all domains with VMP. Mean scores were generally
      improved by the end-of-treatment assessment vs. baseline in both arms. Among
      responding patients, mean scores generally improved from time of response to end
      of-treatment assessment, substantially driven by patients achieving complete
      response (CR). Multivariate analysis showed a significant impact of duration of
      response/CR on improving global health status, pain, and appetite loss scores.
      Analyses by bortezomib dose intensity indicated better HRQoL in patients
      receiving lower dose intensity. CONCLUSIONS: These findings demonstrate
      clinically meaningful, transitory HRQoL decrements with VMP and relatively lower
      HRQoL vs. MP during early treatment cycles, associated with the expected
      additional toxicities. However, HRQoL is not compromised in the long term,
      recovering by the end-of-treatment visit to be comparable vs. MP.

PMID- 22469560
TI  - The effect of different dietary sugars and honey on longevity and fecundity in
      two hyperparasitoid wasps.
AB  - In nature adult insects, such as parasitic wasps or 'parasitoids' often depend on
      supplemental nutritional sources, such as sugars and other carbohydrates, to
      maximize their life-expectancy and reproductive potential. These food resources
      are commonly obtained from animal secretions or plant exudates, including
      honeydew, fruit juices and both floral and extra-floral nectar. In addition to
      exogenous sources of nutrition, adult parasitoids obtain endogenous sources from
      their hosts through 'host-feeding' behavior, whereby blood is imbibed from the
      host. Resources obtained from the host contain lipids, proteins and sugars that
      are assumed to enhance longevity and/or fecundity. Here we conducted an
      experiment exploring the effects of naturally occurring sugars on longevity and
      fecundity in the solitary hyperparasitoids, Lysibia nana and Gelis agilis.
      Although both species are closely related, L. nana does not host-feed whereas G.
      agilis does. In a separate experiment, we compared reproduction and longevity in
      G. agilis reared on either honey, a honey-sugar 'mimic', and glucose.
      Reproductive success and longevity in both hyperparasitoids varied significantly
      when fed on different sugars. However, only mannose- and water-fed wasps
      performed significantly more poorly than wasps fed on four other sugar types. G.
      agilis females fed honey produced twice as many progeny as those reared on the
      honey-sugar mimic or on glucose, whereas female longevity was only reduced on the
      mimic mixture. This result shows not only that host feeding influences
      reproductive success in G. agilis, but also that non-sugar constituents in honey
      do. The importance of non-sugar nutrients in honey on parasitoid reproduction is
      discussed.

PMID- 22469561
TI  - Erythrocytes load of low molecular weight chitosan nanoparticles as a potential
      vascular drug delivery system.
AB  - Low molecular weight (LMW) chitosan nanoparticles have attracted considerable
      attention as colloidal drug carriers, but when applied to intravascular drug
      delivery, they are easy to be removed from circulation by the reticuloendothelial
      system, which limits their applications as long-circulating or target-specific
      carriers. Erythrocytes have a long circulation time in the blood, but they are
      sometimes not suitable for loading and releasing of drug directly. The
      combination of LMW chitosan nanoparticles and erythrocytes that complement each
      other is a desirable strategy to develop a multifunctional drug carrier. In this
      study, monodisperse, LMW chitosan nanoparticles were prepared by ionic gelation
      technique and these nanoparticles were investigated with regard to their
      erythrocyte compatibility. Then the interactions between erythrocytes and
      fluorescence-labeled LMW chitosan nanoparticles were studied by confocal
      microscopy. The results of this study indicate that LMW chitosan nanoparticles
      show good compatibility with erythrocytes and they can be easily attached to the
      surface of erythrocyte membrane, suggesting that erythrocytes load of LMW
      chitosan nanoparticles can be served as a potential vascular drug delivery
      system.

PMID- 22469562
TI  - Multi-digit number processing beyond the two-digit number range: a combination of
      sequential and parallel processes.
AB  - Investigations of multi-digit number processing typically focus on two-digit
      numbers. Here, we aim to investigate the generality of results from two-digit
      numbers for four- and six-digit numbers. Previous studies on two-digit numbers
      mostly suggested a parallel processing of tens and units. In contrast, the few
      studies examining the processing of larger numbers suggest sequential processing
      of the individual constituting digits. In this study, we combined the
      methodological approaches of studies implying either parallel or sequential
      processing. Participants completed a number magnitude comparison task on two-,
      four-, and six-digit numbers including unit-decade compatible and incompatible
      differing digit pairs (e.g., 32_47, 3<4 and 2<7 vs. 37_52, 3<5 but 7>2,
      respectively) at all possible digit positions. Response latencies and fixation
      behavior indicated that sequential and parallel decomposition is not exclusive in
      multi-digit number processing. Instead, our results clearly suggested that
      sequential and parallel processing strategies seem to be combined when processing
      multi-digit numbers beyond the two-digit number range. To account for the
      results, we propose a chunking hypothesis claiming that multi-digit numbers are
      separated into chunks of shorter digit strings. While the different chunks are
      processed sequentially digits within these chunks are processed in parallel.

PMID- 22469563
TI  - The polarization response in InAs quantum dots: theoretical correlation between
      composition and electronic properties.
AB  - III-V  growth and surface conditions strongly influence the physical structure
      and resulting optical properties of self-assembled quantum dots (QDs). Beyond the
      design of a desired active optical wavelength, the polarization response of QDs
      is of particular interest for optical communications and quantum information
      science. Previous theoretical studies based on a pure InAs QD model failed to
      reproduce experimentally observed polarization properties. In this work, multi
      million atom simulations are performed in an effort to understand the correlation
      between chemical composition and polarization properties of QDs. A systematic
      analysis of QD structural parameters leads us to propose a two-layer composition
      model, mimicking In segregation and In-Ga intermixing effects. This model,
      consistent with mostly accepted compositional findings, allows us to accurately
      fit the experimental PL spectra. The detailed study of QD morphology parameters
      presented here serves as a tool for using growth dynamics to engineer the strain
      field inside and around the QD structures, allowing tuning of the polarization
      response.

PMID- 22469564
TI  - Multileaf collimator tracking integrated with a novel x-ray imaging system and
      external surrogate monitoring.
AB  - We have previously developed a tumour tracking system, which adapts the aperture
      of a Siemens 160 MLC to electromagnetically monitored target motion. In this
      study, we exploit the use of a novel linac-mounted kilovoltage x-ray imaging
      system for MLC tracking. The unique in-line geometry of the imaging system allows
      the detection of target motion perpendicular to the treatment beam (i.e. the
      directions usually featuring steep dose gradients). We utilized the imaging
      system either alone or in combination with an external surrogate monitoring
      system. We equipped a Siemens ARTISTE linac with two flat panel detectors, one
      directly underneath the linac head for motion monitoring and the other underneath
      the patient couch for geometric tracking accuracy assessments. A programmable
      phantom with an embedded metal marker reproduced three patient breathing traces.
      For MLC tracking based on x-ray imaging alone, marker position was detected at a
      frame rate of 7.1 Hz. For the combined external and internal motion monitoring
      system, a total of only 85 x-ray images were acquired prior to or in between the
      delivery of ten segments of an IMRT beam. External motion was monitored with a
      potentiometer. A correlation model between external and internal motion was
      established. The real-time component of the MLC tracking procedure then relied
      solely on the correlation model estimations of internal motion based on the
      external signal. Geometric tracking accuracies were 0.6 mm (1.1 mm) and 1.8 mm
      (1.6 mm) in directions perpendicular and parallel to the leaf travel direction
      for the x-ray-only (the combined external and internal) motion monitoring system
      in spite of a total system latency of ~0.62 s (~0.51 s). Dosimetric accuracy for
      a highly modulated IMRT beam--assessed through radiographic film dosimetry-
      improved substantially when tracking was applied, but depended strongly on the
      respective geometric tracking accuracy. In conclusion, we have for the first time
      integrated MLC tracking with x-ray imaging in the in-line geometry and
      demonstrated highly accurate respiratory motion tracking.

PMID- 22469567
TI  - Neuroprotective effect of human placenta-derived cell treatment of stroke in
      rats.
AB  - Human placenta-derived adherent (PDA001) cells are mesenchymal-like stem cells
      isolated from postpartum placenta. In this study, we tested whether intravenously
      infused PDA001 improves neurological functional recovery after stroke in rats. In
      addition, potential mechanisms underlying the PDA001-induced neuroprotective
      effect were investigated. Young adult male rats (2-3 months) were subjected to 2
      h of middle cerebral artery occlusion (MCAo) and treated with PDA001 (4x10(6)) or
      vehicle controls [dextran vehicle or phosphate buffer saline (PBS)] via
      intravenous (IV) administration initiated at 4 h after MCAo. A battery of
      functional tests and measurements of lesion volume and apoptotic cells were
      performed. Immunostaining and ELISA assays for vascular endothelial growth factor
      (VEGF) and hepatocyte growth factor (HGF) and brain derived neurotrophic factor
      (BDNF) were performed in the ischemic brain to test the potential mechanisms
      underlying the neuroprotective effects of PDA001 cell treatment of stroke. PDA001
      cell treatment at 4 h post stroke significantly improved functional outcome and
      significantly decreased lesion volume, TUNEL, and cleaved caspase 3-positive cell
      number in the ischemic brain, compared to MCAo-vehicle and MCAo-PBS control.
      Treatment of stroke with PDA001 cells also significantly increased HGF and VEGF
      expression in the ischemic border zone (IBZ) compared to controls. Using ELISA
      assays, treatment of stroke with PDA001 cells significantly increased VEGF, HGF,
      and BDNF levels in the ischemic brain compared to controls. CONCLUSION: When
      administered intravenously at 4 h after MCAo, PDA001 cells promoted
      neuroprotective effects. These effects induced by PDA001 cell treatment may be
      related to the increase of VEGF, HGF, and BDNF expression,and a decrease of
      apoptosis. PDA001 cells may provide a viable cell source to treat stroke.

PMID- 22469565
TI  - Chronic social isolation in the prairie vole induces endothelial dysfunction:
      implications for depression and cardiovascular disease.
AB  - Humans with depression show impaired endothelium-dependent vasodilation; one
      recent demonstration of which was in the form of a reduced acetylcholine (ACh)
      induced relaxation of adrenergically-precontracted small arteries biopsied from
      older depressed patients. Results from such uses of ACh in general have been
      validated as the most predictive marker of endothelium-related cardiovascular
      diseases. Accordingly, we examined vascular reactivity to ACh in the socially
      isolated prairie vole, a new animal model relevant to human depression and
      cardiovascular disease. Thoracic aortas were carefully dissected from female
      prairie voles after one month of social isolation (versus pairing with a
      sibling). Only aortas that contracted to the adrenergic agent phenylephrine (PE)
      and then relaxed to ACh were evaluated. Among those, ACh-induced relaxations were
      significantly reduced by social isolation (p<0.05), with maximum relaxation
      reaching only 30% (of PE-induced precontraction) compared to 47% in aortas from
      paired (control) animals. Experimental removal of the endothelium from an
      additional set of aortic tissues abolished all ACh relaxations including that
      difference. In these same tissues, maximally-effective concentrations of the
      nitric oxide-donor nitroprusside still completely relaxed all PE-induced
      precontraction of the endothelial-free smooth muscle, and to the same degree in
      tissues from isolated versus paired animals. Finally, in the absence of PE
      induced precontraction ACh did not relax but rather contracted aortic tissues,
      and to a significantly greater extent in tissues from socially isolated animals
      if the endothelium was intact (p<0.05). Thus, social isolation in the prairie
      vole may (1) impair normal release of protective anti-atherosclerotic factors
      like nitric oxide from the vascular endothelium (without altering the inherent
      responsiveness of the vascular smooth muscle to such factors) and (2) cause the
      endothelium to release contracting factors. To our knowledge this is the first
      demonstration of this phenomenon in an animal model of depression induced solely
      by social isolation. These findings have implications for understanding
      mechanisms involved in depression and cardiovascular disease.

PMID- 22469568
TI  - Tim-2 up-regulation and galectin-9-Tim-3 pathway activation in Th2-biased
      response in Schistosoma japonicum infection in mice.
AB  - T cell immunoglobulin domain and mucin domain (Tim) family, a new gene that
      expresses on the surface of T cells, plays a critical role in regulation of T
      cells response. Previous data have shown that Tim-3 expressed on Th1 cells
      promotes itself apoptosis. Tim-2 is preferentially up-regulated during Th2
      differentiation and functions as a potent costimulatory molecule for T-cell
      immunity. The present study aims to learn whether Tims are responsible for Th2
      biased response evoked by Schistosoma japonicum infection. The expressions of Tim
      2 and Tim-3 in spleen lymphocytes from S. japonicum-infected mice were examined,
      and the possible role of galectin-9-Tim-3 pathway in Th2-biased response
      triggered by schistosome infection was discussed. Our results showed that Tim-2
      mRNAs were up-regulated in the spleen of schistosome-infected mice, which
      coincided with elevated IL-4 gene expression. Administration of galectin-9
      significantly induced apoptosis of naive spleen lymphocytes with down-regulation
      IFN-gammaexpression in vitro. Additionally, Tim-3-Fc fusion protein notably
      enhanced Th1 cells and decreased Th2 cells in vitro. Thus, we concluded that pro
      apoptotic effects on Th1 population through galectin-9-Tim-3 pathway and the up
      regulation of Tim-2 on Th2 cells might be critical to Th2-biased response of host
      with schistosomiasis japonica.

PMID- 22469569
TI  - Geographic distribution of hantaviruses associated with neotomine and
      sigmodontine rodents, Mexico.
AB  - To increase our knowledge of the geographic distribution of hantaviruses
      associated with neotomine or sigmodontine rodents in Mexico, we tested 876
      cricetid rodents captured in 18 Mexican states (representing at least 44 species
      in the subfamily Neotominae and 10 species in the subfamily Sigmodontinae) for
      anti-hantavirus IgG. We found antibodies against hantavirus in 35 (4.0%) rodents.
      Nucleotide sequence data from 5 antibody-positive rodents indicated that Sin
      Nombre virus (the major cause of hantavirus pulmonary syndrome [HPS] in the
      United States) is enzootic in the Mexican states of Nuevo Leon, San Luis Potosi,
      Tamaulipas, and Veracruz. However, HPS has not been reported from these states,
      which suggests that in northeastern Mexico, HPS has been confused with other
      rapidly progressive, life-threatening respiratory diseases. Analyses of
      nucleotide sequence data from 19 other antibody-positive rodents indicated that
      El Moro Canyon virus and Limestone Canyon virus are geographically widely
      distributed in Mexico.

PMID- 22469570
TI  - Neutrophil gelatinase-associated lipocalin: a more specific assay is needed for
      diagnosing renal injury.

PMID- 22469571
TI  - Verruciform xanthoma of the glans penis mimicking squamous cell carcinoma - role
      of scavenger receptor positive macrophages.

PMID- 22469572
TI  - Upper tract urothelial carcinoma: current treatment and outcomes.
AB  - The reference standard treatment of upper tract urothelial carcinoma is open
      radical nephroureterectomy. Many centers have advocated less-invasive treatment
      modalities. We reviewed contemporary treatments of upper tract urothelial
      carcinoma and their outcomes. A MEDLINE search was conducted for all relevant
      published data during the past 15 years. Endoscopic management is feasible for
      low-grade disease with strict surveillance protocols. Radical nephroureterectomy
      remains the reference standard for upper tract urothelial carcinoma. The
      intermediate-term oncologic outcomes are similar between the laparoscopic and
      open approaches. Controversies still exist regarding the optimal management of
      the distal ureter, the utility of topical therapy, and the role of
      lymphadenectomy.

PMID- 22469573
TI  - Annual prostatectomy volume is related to rectal laceration rate after radical
      prostatectomy.
AB  - OBJECTIVE: To examine the effect of annual prostatectomy volume (APV) on
      contemporary intraoperative rectal laceration (RL) rates after radical
      prostatectomy. METHODS: From 1999 to 2008, 36 699 radical prostatectomy
      procedures were performed in Florida. First, logistic regression models
      predicting the RL rate were fitted. Second, other logistic regression models were
      used to examine the association between RL and 2 other secondary outcomes:
      prolonged length of stay (>3 days) and increased hospital charges (>$37 621). The
      covariates included APV quintiles, surgical approach (minimally invasive vs open
      radical prostatectomy), lymph node dissection status, age, year of surgery, race,
      and baseline Charlson comorbidity index. RESULTS: The overall RL rate was 0.7%.
      The RL rate was 0.3%, 0.6%, 0.7%, 0.9%, and 1.0% for the very high, high,
      intermediate, low, and very low APV quintiles, respectively (P < .001). In
      multivariate analyses predicting RL, patients treated by intermediate (odds ratio
      2.39, P = .003), low (odds ratio 2.95, P < .001), and very low (odds ratio 3.26,
      P < .001) APV surgeons had a greater likelihood of experiencing an RL relative to
      patients treated by very high APV surgeons. Second, in the multivariate analyses,
      patients with a RL were 9.1-fold more likely to have a prolonged length of stay
      (P < .001) and were 3.4-fold more likely to have increased total hospital charges
      (P < .001). CONCLUSION: A greater APV exerts a protective effect on RL rates.
      Additionally, RL increases the length of stay and hospital charges.

PMID- 22469575
TI  - Editorial comment.

PMID- 22469576
TI  - Program for laparoscopic urologic skills: a newly developed and validated
      educational program.
AB  - OBJECTIVE: To develop and evaluate a program for laparoscopic urologic skills
      (PLUS) to determine the face, content, and construct validation to achieve
      uniformity and standardization in training residents in urology. METHODS: The
      PLUS consists of 5 basic laparoscopic tasks. Three tasks were abstracted from the
      Fundamentals of Laparoscopic Surgery program, and 2 additional tasks were
      developed under continuous evaluation by expert urologists. Fifty participants
      were recruited from different hospitals and performed the final PLUS training.
      They all completed a questionnaire after performance. Three outcome parameters
      were measured: performance quality, time, and dropped objects. The relationship
      between laparoscopic experience and the outcome parameters was investigated.
      RESULTS: Of the 50 participants, 13 were students, 20 were residents, and 17 were
      urologists. Double-log linear regression analysis for all 5 tasks showed a
      significant effect (effect size range 0.53-0.82; P < .0005) for laparoscopic
      experience on performance time. Substantial correlations were found between
      experience and quality ratings (log-linear regression effect size 0.37; P = .012)
      and the number of dropped objects (Spearman correlation effect size 0.49; P <
      .01). The usefulness of the PLUS model as a training tool for basic laparoscopic
      skills was rated 4.55 on a scale from 1 (not useful) to 5 (useful) (standard
      deviation 0.58; range 3-5). CONCLUSION: The results of the present study
      indicated the face, content, and construct validity for the PLUS. The training is
      considered appropriate for use as a primary training tool for an entry test or as
      part of a step-wise training program in which basic and procedural laparoscopic
      skills are integrated.

PMID- 22469577
TI  - Intraoperative mannitol use does not improve long-term renal function outcomes
      after minimally invasive partial nephrectomy.
AB  - OBJECTIVE: To evaluate intravenous mannitol during minimally invasive partial
      nephrectomy (PN) by comparing the renal function outcomes of the patients who
      received it versus those who did not. METHODS: Of 285 consecutive elective
      minimally invasive PN cases from February 2005 to July 2010, 164 patients (58%)
      were treated with mannitol. We compared the renal function recovery using a
      multivariate generalized estimating equation linear model of estimated glomerular
      filtration rate (eGFR) controlling for nephrometry complexity, preoperative eGFR,
      American Society of Anesthesiologists score, ischemia time, estimated blood loss,
      age, and sex. Sensitivity analyses were performed to adjust for cold ischemia and
      individual surgeon differences corrected for year of surgery. RESULTS: Of the 285
      patients who underwent minimally invasive treatment, 164 received mannitol and
      121 did not. Those who received mannitol had a better preoperative eGFR (median
      72 vs 69 mL/min/m(2), P = .046), less complex nephrometry scores (P = 0.051), and
      were less likely to have an American Society of Anesthesiologists score of >= 3
      (42% vs 54%, P = .005). Renal function recovery was similar in both groups
      (estimated effect of mannitol -0.7 mL/min/m(2), 95% confidence interval -3.6-2.2,
      P = .6). At no point in the postoperative period did mannitol make a significant
      difference in the eGFR according to the generalized estimating equation model
      after adjusting for multiple potential renal function confounders. CONCLUSION:
      Mannitol use did not influence renal function recovery within 6 months of
      minimally invasive PN as measured by the eGFR in our analysis. An appropriately
      designed prospective study of mannitol is being conducted to validate its use
      during PN.

PMID- 22469578
TI  - Editorial comment.

PMID- 22469580
TI  - Microsurgical testis-sparing surgery in small testicular masses: seven years
      retrospective management and results.
AB  - OBJECTIVE: To retrospectively evaluate the clinical outcomes of 20 patients
      diagnosed with a nonpalpable or small testicular mass (2 cm) at 2 academic
      urological department. Testis-sparing surgery (TSS) is currently performed
      routinely for the management of nonpalpable testicular masses. High reliability
      of frozen section examination (FSE) and high-frequency ultrasound (US) and the
      adoption of microsurgical techniques improved safety and feasibility of this
      technique. METHODS: From January 2004 to March 2011, 23 patients underwent
      microsurgical TSS. An inguinal approach was performed in 22 cases and a
      suprapubic incision in one bilateral case. All procedures were performed with an
      operating microscope, with warm ischemia in 21 cases and cold ischemia in 2
      cases. Intraoperative US was performed before opening the albuginea. Mean
      operative time was 89 minutes. RESULTS: After mass excision, FSE was performed;
      only 2 seminomatous tumors were identified, and the remaining masses were benign
      lesions. After a mean follow-up >12 months, all patients are free of disease; no
      hypogonadism developed. CONCLUSIONS: TSS performed using an operating microscope
      allowed the preservation of testes for 21 patients diagnosed with small
      testicular and/or nonpalpable mass (<2 cm), without evidence of disease
      recurrence or de novo onset. This approach could be mandatory in the treatment of
      bilateral tumors or in solitary testis. Maintaining fertility is not the main
      goal of TSS because a great number of patients affected by testicular tumors are
      already infertile. Esthetic outcomes and sparing hormonal function are the main
      reasons for TSS.

PMID- 22469581
TI  - Editorial comment.

PMID- 22469582
TI  - Editorial comment.

PMID- 22469584
TI  - Preliminary short-term outcomes of a modified double-T ileal continent cutaneous
      urinary diversion using Yang-Monti tube implantation through serosa-lined
      extramural tunnel: the PGIMER pouch.
AB  - OBJECTIVE: To present our simplified technical modification of double-T continent
      cutaneous diversion (CCD) using Yang-Monti tubes. METHODS: During 2008-2011, 8
      adult patients underwent CCD; 4 had classical exstrophy, 2 bladder cancer, 1
      recurrent vaginal cancer post-radiotherapy, and 1 prostate cancer with post
      simple retropubic prostatectomy urethral stricture with incontinence. For
      reconstruction, a 45- to 50-cm segment of terminal ileum sparing 25 cm of
      terminal ileum was harvested. Its distal 3- to 6-cm and proximal 3-cm segments
      were separated on vascular pedicle and fashioned into Yang-Monti tubes (1
      proximally and 1 or 2 distally). The middle 40- to 45-cm detubularized segment
      was fashioned into a "W" shape, and serosal aspects of adjacent loops were
      sutured together close to the mesentery. The tubes were implanted into the W
      pouch via extramural serosa-lined tunnel (Abol-Enein and Ghoneim). The pouch was
      closed transversely over an 18-Fr pouchostomy and 16-Fr stomal catheter. The
      ureters were implanted into the proximal tube using the Wallace principle, over 6
      to 8-Fr infant feeding tubes exteriorized through the pouch. The distal end of
      the distal tube was made into a flush stoma. RESULTS: In the early postoperative
      period, intestinal obstruction (2 cases), ureteroileal anastomotic leakage (3
      cases) and vesico-ileocutaneous fistula (1 case) were encountered. No
      ureteroileal anastomotic obstruction or catherization-related difficulty was
      observed until the last follow-up (2 months to 3 years). Of 15 anastomoses, 14
      were nonrefluxing. CONCLUSION: Ileal double-T CCD using the Yang-Monti principle
      is technically feasible and relatively simple, particularly in nonirradiated
      ileum. However, early complications indicate a learning curve, and long-term
      follow-up and larger data are needed.

PMID- 22469586
TI  - Re: Marchini et al.: Silent ureteral stones: effect on kidney function--can
      treatment of silent ureteral stones preserve kidney function? (Urology
      2012;79:304-308).

PMID- 22469588
TI  - Re: Khairy-Salem et al.: Semirigid ureteroscopy in management of large proximal
      ureteral calculi: is there still a role in developing countries? (Urology
      2011;77:1064-1069).

PMID- 22469589
TI  - Re: Kreshover et al.: Predictors for negative ureteroscopy in the management of
      upper urinary tract stone disease (Urology 2011;78:748-752).

PMID- 22469591
TI  - Commentary on: A controlled trial of a nurse follow-up dietary intervention on
      maintaining a heart-healthy dietary pattern among patients after myocardial
      infarction.

PMID- 22469592
TI  - Synthesis and herbicidal activity evaluation of novel beta-carboline derivatives.
AB  - Based on the original structure of harmine, several novel 1,2,3,4-tetrahydro-beta
      carboline, beta-carboline and 1-substituted-beta-carboline derivatives bearing a
      substituted carbohydrazide group at C-3 were designed and synthesized to
      investigate the structure-activity relationship of their analogues. All of the
      compounds were characterized by infrared (IR), proton and carbon nuclear magnetic
      resonance (1H-NMR, 13C-NMR), and mass spectroscopy (MS). The bioassay tests
      showed that N'-benzylidene-1-phenyl-beta-carboline-3-carbohydrazide
      (C(25)H(18)N(4)O, m.w. 390.4) (c2) and N'-(4-trifluoromethyl-benzylidene)-1
      phenyl-beta-carboline-3-carbohydrazide (C(26)H(17)N(4)OF(3), m.w. 458) (d2)
      exhibited good inhibitory activity against dicotyledonous and monocotyledonous
      weeds, with EC(50) values of 4.83 uM and 14.25 uM, respectively.

PMID- 22469593
TI  - Diverse effects of beta-carotene on secretion and expression of VEGF in human
      hepatocarcinoma and prostate tumor cells.
AB  - Oral administration of beta-carotene (BC) was found to exert opposite effects on
      plasma levels of vascular endothelial growth factor (VEGF) in two animal models.
      One study in nude mice injected via tail vein with hepatocarcinoma SK-Hep-1 cells
      showed that BC decreases the plasma VEGF level, whereas the other study in nude
      mice injected subcutaneously with prostate tumor PC-3 cells showed that BC
      increases the plasma VEGF level. Herein we investigated whether BC (0.5-20 MUM)
      possesses diverse effects on VEGF secretion in SK-Hep-1, PC-3 and melanoma B16F10
      cells. We found that incubation of SK-Hep-1 cells with BC (1-20 MUM) for 6 h
      significantly decreased VEGF secretion, whereas BC (1-10 MUM) significantly
      increased the VEGF secretion in PC-3 cells. However, these effects disappeared at
      12 h of incubation. Similar effects occurred in VEGF mRNA and protein expression
      after treatment of SK-Hep-1 and PC-3 cells with BC for 6 h. In contrast, BC (0.5
      20 MUM) did not affect mRNA and protein expression and secretion of VEGF in
      B16F10 cells. We also found that the proliferation of SK-Hep-1 and B16F10 cells
      was significantly inhibited by 20 MUM BC at 6 and 12 h of incubation, whereas the
      proliferation of PC-3 cells was significantly inhibited by 20 MUM BC at 12 h of
      incubation. In summary, the present study demonstrated the tumor-specific effect
      of BC on VEGF secretion in different cancer cell lines.

PMID- 22469594
TI  - Essential oils in combination and their antimicrobial properties.
AB  - Essential oils (EOs) have been long recognized for their antibacterial,
      antifungal, antiviral, insecticidal and antioxidant properties. They are widely
      used in medicine and the food industry for these purposes. The increased interest
      in alternative natural substances is driving the research community to find new
      uses and applications of these substances. EOs and their components show
      promising activities against many food-borne pathogens and spoilage
      microorganisms when tested in vitro. In food systems, higher concentrations of
      EOs are needed to exert similar antibacterial effects as those obtained in in
      vitro assays. The use of combinations of EOs and their isolated components are
      thus new approaches to increase the efficacy of EOs in foods, taking advantage of
      their synergistic and additive effects. The purpose of this review is to provide
      an overview on the antimicrobial efficacy of these combinations. A survey of the
      methods used for the determination of the interactions and mechanisms involved in
      the antimicrobial activities of these combinations are also reported.

PMID- 22469595
TI  - A simple halide-to-anion exchange method for heteroaromatic salts and ionic
      liquids.
AB  - A broad and simple method permitted halide ions in quaternary heteroaromatic and
      ammonium salts to be exchanged for a variety of anions using an anion exchange
      resin (A(-) form) in non-aqueous media. The anion loading of the AER (OH(-) form)
      was examined using two different anion sources, acids or ammonium salts, and
      changing the polarity of the solvents. The AER (A(-) form) method in organic
      solvents was then applied to several quaternary heteroaromatic salts and ILs, and
      the anion exchange proceeded in excellent to quantitative yields, concomitantly
      removing halide impurities. Relying on the hydrophobicity of the targeted ion
      pair for the counteranion swap, organic solvents with variable polarity were
      used, such as CH(3)OH, CH(3)CN and the dipolar nonhydroxylic solvent mixture
      CH(3)CN:CH(2)Cl(2) (3:7) and the anion exchange was equally successful with both
      lipophilic cations and anions.

PMID- 22469596
TI  - Naucline, a new indole alkaloid from the bark of Nauclea officinalis.
AB  - A new indole alkaloid, naucline (1) together with four known alkaloids, angustine
      (2), angustidine (3), nauclefine (4) and naucletine (5), were isolated from the
      bark of Nauclea officinalis. The structures of all isolated compounds were
      elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and
      LCMS-IT-TOF. In addition to that of alkaloid 1, the complete 13C-NMR data of
      naucletine (5) were also reported. Naucline (1) showed a moderate vasorelaxant
      activity (90% relaxation at 1 * 10(-5) M) whereas, angustine (2), nauclefine (4),
      and naucletine (5) showed potent vasorelaxant activity (more than 90% relaxation
      at 1 * 10(-5) M) on an isolated rat aorta.

PMID- 22469597
TI  - Phytotoxic effects and a phytotoxin from the invasive plant Xanthium italicum
      Moretti.
AB  - The allelopathic effects of different parts of the plant Xanthium italicum
      Moretti were evaluated by conducting bioassays against two dicot plants, amaranth
      (Amaranthus mangostanus L.) and lettuce (Lectuca sativa L.), and two monocot
      plants, wheat (Triticum aestivum Linn) and ryegrass (Lolium multiforum). Leaf and
      fruit extract possessed the strongest biological activity, killing all seeds of
      four test species at 0.05 g/mL concentration. Fruits were chosen for further
      investigation because of their high biomass. This led to the isolation and
      identification of a phytotoxin-Xanthinosin-a known sesquiterpene lactone.
      Xanthinosin significantly affected seedling growth of all test species at 160 uM
      concentration. Cultivating seeds in 800 MUM xanthinosin solution resulted in a
      great decrease in seedling growth of all test species, especially for the two
      dicot plants, amaranth and lettuce, whose root length was inhibited by 78% and
      89%, respectively. By comparison, the numbers were 69% lower for wheat, and 66%
      for ryegrass, two monocot plants. When treated with 4 mM xanthinosin solution,
      seed germination of all test plants was almost completely inhibited. The
      possibility of utilizing xanthinosin as an eco-friendly herbicide was discussed.

PMID- 22469598
TI  - Advanced fluorescence microscopy techniques--FRAP, FLIP, FLAP, FRET and FLIM.
AB  - Fluorescence microscopy provides an efficient and unique approach to study fixed
      and living cells because of its versatility, specificity, and high sensitivity.
      Fluorescence microscopes can both detect the fluorescence emitted from labeled
      molecules in biological samples as images or photometric data from which
      intensities and emission spectra can be deduced. By exploiting the
      characteristics of fluorescence, various techniques have been developed that
      enable the visualization and analysis of complex dynamic events in cells,
      organelles, and sub-organelle components within the biological specimen. The
      techniques described here are fluorescence recovery after photobleaching (FRAP),
      the related fluorescence loss in photobleaching (FLIP), fluorescence localization
      after photobleaching (FLAP), Forster or fluorescence resonance energy transfer
      (FRET) and the different ways how to measure FRET, such as acceptor bleaching,
      sensitized emission, polarization anisotropy, and fluorescence lifetime imaging
      microscopy (FLIM). First, a brief introduction into the mechanisms underlying
      fluorescence as a physical phenomenon and fluorescence, confocal, and multiphoton
      microscopy is given. Subsequently, these advanced microscopy techniques are
      introduced in more detail, with a description of how these techniques are
      performed, what needs to be considered, and what practical advantages they can
      bring to cell biological research.

PMID- 22469599
TI  - EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A
      summary for otorhinolaryngologists.
AB  - The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update
      of similar evidence based position papers published in 2005 and 2007. The
      document contains chapters on definitions and classification, we now also
      proposed definitions for difficult to treat rhinosinusitis, control of disease
      and better definitions for rhinosinusitis in children. More emphasis is placed on
      the diagnosis and treatment of acute rhinosinusitis. Throughout the document the
      terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic
      rhinosinusitis with nasal polyps (CRSwNP) are used to further point out
      differences in pathophysiology and treatment of these two entities. There are
      extensive chapters on epidemiology and predisposing factors, inflammatory
      mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis,
      aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal
      rhinosinusitis and the relationship between upper and lower airways. The chapters
      on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but
      not least all available evidence for management of acute rhinosinusitis and
      chronic rhinosinusitis with or without nasal polyps in adults and children is
      analyzed and presented and management schemes based on the evidence are proposed.
      This executive summary for otorhinolaryngologists focuses on the most important
      changes and issues for otorhinolaryngologists. The full document can be
      downloaded for free on the website of this journal:
      http://www.rhinologyjournal.com.

PMID- 22469600
TI  - Assessment of chemosensory function using electroencephalographic techniques.
AB  - Electroencephalographic techniques are widely used to provide an objective
      evaluation of the chemosensory function and to explore neural mechanisms related
      to the processing of chemosensory events. The most popular technique to evaluate
      brain responses to chemosensory stimuli is across trial time-domain averaging to
      reveal chemosensory event-related potentials (CSERP) embedded within the ongoing
      EEG. Nevertheless, this technique has a poor signal-to-noise ratio and cancels
      out stimulus-induced changes in the EEG signal that are not strictly phased
      locked to stimulus onset. The fact that consistent CSERP are not systematically
      identifiable in healthy subjects currently constitutes a major limitation to the
      use of this technique for the diagnosis of chemosensory dysfunction. In this
      review, we will review the different techniques related to the recording and
      identification of CSERP, discuss some of their limitations, and propose some
      novel signal processing methods which could be used to enhance the signal-to
      noise ratio of chemosensory event-related brain responses.

PMID- 22469601
TI  - Normal peak nasal inspiratory flow rate values in healthy children aged 6 to 11
      years in the Netherlands.
AB  - BACKGROUND: The measurement of peak nasal inspiratory flow (PNIF) is a simple,
      quick, easy to perform and cheap tool for determining the extent of nasal airway
      patency. However, normative data are rare and not available for Dutch children
      aged 6 to 11 years. METHODS: Repeated PNIF measurements were obtained from 212
      Dutch children of primary school age. Of these 212 children, 166 fulfilled the
      inclusion criteria of our study. The influence of age, gender, ethnicity, weight
      and height on PNIF was studied. RESULTS: Age is the only parameter of influence
      on PNIF. All other parameters do not influence PNIF. Normative data are
      presented. CONCLUSION: PNIF measurements are possible in children aged six years
      and older. Age does influence PNIF, but gender, weight, height and ethnicity do
      not.

PMID- 22469602
TI  - Non-invasive diagnostics of the maxillary and frontal sinuses based on diode
      laser gas spectroscopy.
AB  - PROBLEM: Suspected, but objectively absent, rhinosinusitis constitutes a major
      cause of visits to the doctor, high health care costs, and the over-prescription
      of antibiotics, contributing to the serious problem of resistant bacteria. This
      situation is largely due to a lack of reliable and widely applicable diagnostic
      methods. METHOD: A novel method for the diagnosis of rhinosinusitis based on non
      intrusive diode laser gas spectroscopy is presented. The technique is based on
      light absorption by free gas (oxygen and water vapour) inside the sinuses, and
      has the potential to be a complementary diagnostic tool in primary health care.
      The method was evaluated on 40 patients with suspected sinus problems, referred
      to the diagnostic radiology clinic for low-dose computed tomography (CT), which
      was used as the reference technique. MAIN RESULTS: The data obtained with the new
      laser-based method correlated well with the grading of opacification and
      ventilation using CT. The sensitivity and specificity were estimated to be 93%
      and 61%, respectively, for the maxillary sinuses, and 94% and 86%, respectively,
      for the frontal sinuses. Good reproducibility was shown. PRINCIPAL CONCLUSION:
      The laser-based technique presents real-time clinical data that correlate well to
      CT findings, while being non-intrusive and avoiding the use of ionizing
      radiation.

PMID- 22469603
TI  - The impact of allergic rhinitis on symptoms,  and  quality of life using the new
      criterion of ARIA severity classification.
AB  - INTRODUCTION: Allergic rhinitis (AR) is a common disease with major socieconomic
      burden and a significant impact on quality of life. OBJECTIVE: The objective of
      the study was to assess the impact of AR severity, using the modified ARIA (m
      ARIA) severity criterion in order to discriminate among moderate and severe AR,
      in symptoms and quality of life assessed with the questionnaire ESPRINT-15.
      METHODS: The specific quality of life questionnaire (ESPRINT-15) was applied in
      over thousand untreated RA patients. Severity was evaluated by the m-ARIA
      classification, which categorizes AR as mild, moderate, and severe. Nasal
      symptoms were evaluated by using categorized (none, low, middle, and high) Total
      Four Symptom Score (T4SS). RESULTS: Using the m-ARIA severity classification,
      significant differences in quality of life, both global score and specific
      domains, and categorized T4SS were found among the AR severity groups.
      CONCLUSION: Modified ARIA severity classification in mild, moderate, and severe
      allergic rhinitis clearly discriminates the impact of AR in all domains of
      quality of life and categorized symptom's score.

PMID- 22469604
TI  - Cyclamen europaeum nasal spray, a novel phytotherapeutic product for the
      management of acute rhinosinusitis: a randomized double-blind, placebo-controlled
      trial.
AB  - AIM: To evaluate the efficacy and safety of a phytotherapeutic nasal spray
      containing Cyclamen europaeum (CE) in the treatment of acute rhinosinusitis
      (ARS). MATERIAL/METHODS: We performed a randomized, double-blind, placebo
      controlled trial of CE nasal spray once daily for 15 days in 99 adult patients
      with moderate-to-severe ARS who also received amoxicillin 500 mg three times
      daily for the first 8 days. The primary endpoint was the change in mean total
      symptom scores (TSS) on day 7. Secondary endpoints included individual symptom
      scores (nasal congestion, mucus secretion, facial pain, impairment of smell) and
      endoscopic findings on days 7 and 15 and others. RESULTS: No statistically
      significant difference in TSS was noted for CE versus placebo on day 7. Moreover,
      the individual scores were not statistically different between the groups for the
      ITT-population on day 7. However, both a reduction in facial pain and an
      improvement in endoscopically-assessed mucosal obstruction significantly favoured
      CE on day 7. The most common adverse events were nasal burning and mild
      epistaxis, but no severe adverse events were documented. CONCLUSION: In summary,
      this is the first randomized controlled trial on phytotherapy in patients with
      moderate-to-severe ARS demonstrating clinical safety and some encouraging effects
      of CE which merit to investigate phytotherapeutic products in further large-scale
      clinical trials.

PMID- 22469605
TI  - Long-term low-dose antibiotics in recalcitrant chronic rhinosinusitis: a
      retrospective analysis.
AB  - INTRODUCTION: In recalcitrant Chronic RhinoSinusitis (CRS) treatment with
      intranasal corticosteroids, short-term antibiotics and even sinus surgery is
      frequently insufficient. Long-term low-dose administration of antibiotics has
      been suggested as a treatment option in these patients. We analysed the
      outpatient clinic population treated with different long-term low-dose
      antibiotics at the AMC Amsterdam. PATIENTS AND METHODS: Eligible patients, who
      were treated with trimethoprim-sulfamethoxazole or macrolides, were
      retrospectively identified from our outpatient clinic in 2009. The two main
      outcome measures were sinonasal complaints and nasal endoscopic findings. A 5
      point grading scale was used to score the results compared with the pre-treatment
      situation. This was measured at several time-points during, and after the
      antibiotic course, and at the end of the follow-up term. RESULTS: Seventy-six
      patients were included, 53 per cent had asthma and all of them had undergone
      sinus surgery. Seventy-eight per cent showed improvement of the symptoms, and 84
      per cent demonstrated improvement of the sinonasal mucosa at the end of the
      course. No significant difference was found between the trimethoprim
      sulfamethoxazole and macrolide group. DISCUSSION: Long-term low-dose treatment
      with antibiotics seems to improve CRS symptoms and the appearance of the
      sinonasal mucosa on nasal endoscopy. However, at this stage, strong conclusions
      are immature because no placebo-group has been included. Despite increasing use
      of long-term low-dose treatment of recalcitrant CRS in referral centres, hard
      clinical evidence is lacking. More research is urgently required.

PMID- 22469606
TI  - Long-term effects of cutting versus non-cutting instruments in FESS.
AB  - BACKGROUND: Currently most ENT surgeons advocate using cutting instruments in
      Functional Endoscopic Sinus Surgery (FESS), based on the assumption of superior
      wound healing due to mucosal preservation. However, there is no scientific
      evidence of superiority of the cutting instruments. METHODS: A prospective,
      randomized double blinded study was performed in 100 patients undergoing FESS,
      operated one side with non-cutting and the contra lateral side with cutting
      instruments. After a mean follow-up of 12 years after FESS, unilateral and global
      sino-nasal symptoms were scored by the patients using VAS, endoscopic
      abnormalities scored at both sides at the Outpatient clinic and radiologic
      abnormalities were described. RESULTS: No significant differences between the
      sides operated by cutting and non-cutting instruments were found for sino-nasal
      symptomatic or for radiologic abnormalities between both sides. For the
      endoscopic parameters there was no difference for secretion or mucosa. Only for
      the presence of endoscopic synechiae there was a statistically significant
      difference between both groups. At the non-cutting side more synechiae were
      noticed, but no interference with sinus access, neither ventilation nor drainage
      was observed. CONCLUSION: FESS performed with cutting instruments results in less
      synechiae formation compared to non-cutting instruments. However, the presence of
      synechiae is not associated with more symptoms or CT scan abnormalities.

PMID- 22469607
TI  - Long-term follow-up of posttraumatic olfactory disorders.
AB  - OBJECTIVE: This study aims to determine the long-term recovery rate of
      posttraumatic olfactory disorders and to evaluate whether a lateralized disorder
      influences recovery. METHOD: Olfactory function of 67 patients with posttraumatic
      olfactory disorders were examined twice using the 'Sniffin' Sticks' test battery.
      Olfactory function was classified based on composite TDI (Threshold,
      Discrimination and Identification) score. Subjective impairment was rated by
      visual analogue scale ranging from 0 to 10. RESULTS: First and second
      examinations were conducted an average of 16.7 months and 74 months after trauma,
      respectively. From first to second examination, mean TDI score of the better
      nostril increased significantly, the number of patients with anosmia of the
      better nostril decreased, and number of hyposmic and normosmic patients
      increased. Subjective impairment decreased. Neither age, sex, nor side
      differences between nostrils affected improvement. CONCLUSION: After the follow
      up period, in 27% of the patients the TDI score improved &#8805; 6 points score
      and subjective impairment decreased. A follow-up period of more than 2 years is
      recommended.

PMID- 22469608
TI  - Low meningitis-incidence in primary spontaneous compared to secondary
      cerebrospinal fluid rhinorrhoea.
AB  - OBJECTIVE: Spontaneous cerebrospinal fluid (CSF) rhinorrhoea is a separate
      clinical entity with elevated intracranial pressure as its most probable
      pathophysiological mechanism. Having the clinical impression of distinct courses
      of diseases in primary spontaneous (PS) compared to secondary CSF rhinorrhoea,
      our objective was to identify whether the two forms differ in the duration of CSF
      rhinorrhoea and the incidence of meningitis. METHODS: Chart review performed on
      all patients referred with a CSF leak to our tertiary-care medical center over a
      20-year period from 1990 to 2010. RESULTS: In total, 58 cases suffering from CSF
      rhinorrhoea could be included. The aetiology was primary spontaneous in 23 (40%)
      and secondary in 35 (60%) patients. The duration of CSF rhinorrhoea was notably
      longer in patients with PS CSF rhinorrhoea. Moreover, we could show a
      significantly lower incidence of meningitis with PS CSF rhinorrhoea compared to
      the secondary group (annual incidence of 0.12 vs. 1.22 episodes). CONCLUSION: A
      significantly lower incidence and delayed onset of meningitis in patients
      suffering from PS CSF rhinorrhoea could be explained by an elevated intracranial
      pressure that hinders the ascension of bacteria. The closure of a leak in
      secondary CSF fistula seems more urgent than in PS CSF fistulas.

PMID- 22469609
TI  - Local sclerotherapy with polydocanol (Aethoxysklerol(r)) for the treatment of
      Epistaxis in Rendu-Osler-Weber or Hereditary Hemorrhagic Telangiectasia (HHT): 15
      years of experience.
AB  - Hereditary Haemorrhagic Telangiectasia or Rendu-Osler-Weber syndrome is a rare
      autosomal dominant vascular disease characterized by mucocutaneous and
      gastrointestinal telangiectases and localized arteriovenous malformations in
      lung, brain and liver. Epistaxis, due to rupture of telangiectases of the nasal
      mucosa, is the most frequent clinical manifestation, leading in many cases to
      severe impairment of the quality of life in the patients. Though several
      treatments have been used to reduce epistaxis, none have been completely
      effective, with the exception of polydocanol (Aethoxysklerol(r)) in submucosal or
      subpericondrial injections, which was first presented in 2000 with very good
      results. After fifteen years using polydocanol in submucosal injections on 45
      patients and with nearly 300 injections, we have observed that in 95% of all
      cases, their nose bleeds improved with respect to frequency and quantity without
      any important side effects. There was just one case of septal perforation,
      another with increased septal perforation, and one patient who suffered from
      dizziness and blurred vision for a few minutes. In this paper the results
      obtained using this technique over a fifteen-year period will be presented and
      evaluated.

PMID- 22469610
TI  - Human papillomavirus load and physical status in sinonasal inverted papilloma and
      squamous cell carcinoma.
AB  - BACKGROUND: This study investigated prospectively the role of human
      papillomavirus (HPV) in paranasal inverted papilloma (IP). METHODS: HPV presence
      and viral load and physical status of HPV-16 were examined by polymerase chain
      reaction-based methods using fresh frozen samples obtained from 13 patients with
      IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group)
      and 39 with chronic inflammatory lesions (inflammatory group). RESULTS: The
      presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in
      the IP, SCC and inflammatory groups, respectively. The IP group showed
      significantly higher HPV-positive rates than the inflammatory group. All types of
      HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy
      numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was
      higher in the IP and SCC groups than in the inflammatory group. In the IP group,
      no significant relationship was found between HPV-16 viral load and clinical
      characteristics, or between physical status and clinical characteristics. One
      patient with IP and concomitant squamous cell carcinoma, however, showed high
      viral load and integration. CONCLUSIONS: HPV infection is involved in the
      pathogenesis of IP, and high viral load and integration of HPV have an important
      role in malignant lesion in association with IP.

PMID- 22469611
TI  - Treatment of juvenile angiofibromas: 18-year experience of a single tertiary
      centre in Spain.
AB  - BACKGROUND: The management of juvenile angiofibroma (JA) has changed during the
      last decades but it still continues to be a challenge. The objective of this
      study was to review the used treatment and our outcomes. METHODS: From 1992 to
      2010, 48 cases of JA were treated at our department. Charts were reviewed for
      standard demographic, tumour size and location, vascular supply and results of
      embolization, surgical approach, operative results, adjuvant therapies,
      recurrence and postoperative follow-up. RESULTS: Most tumours were Andrews-Fisch
      stages III and IV and surgery was used as the main treatment in all cases. We
      used an open surgical approach in 37 (77%) patients and 11 (23%) were treated
      endoscopically. The most common open approach used in this series was the
      subtemporal-preauricular approach. Until 1995, all tumours were operated on by a
      conventional open approach. Afterwards, early-stage tumours were operated on
      through an endoscopic approach. Ten patients were treated through surgery
      followed by radiosurgery. Two (4%) patients had recurrent disease. CONCLUSIONS:
      These tumours should be treated at centres with expertise in skull base surgery
      to achieve complete surgical resections with low morbidity. Radiosurgery after
      surgery seems to be a valuable option in the long-term control of some extended
      JAs.

PMID- 22469612
TI  - Canine fossa trephine is a beneficial procedure in patients with Samter's triad.
AB  - BACKGROUND: Canine fossa trephine (CFT) is an adjunctive technique to sinus
      surgery in patients with recalcitrant maxillary sinusitis. CFT allows for disease
      clearance in areas of the maxillary sinus that are hard to reach with standard
      endoscopic techniques. The objective of this study was to compare the surgical
      outcome of CFT to standard middle meatal antrostomy (MMA) in matched patients
      with the severely diseased maxillary sinus. STUDY DESIGN: Prospective clinical
      study METHODS: Patients undergoing sinus surgery were enrolled in either the CFT
      or MMA group. All patients had nasal polyps, Lund Mackay score of 2 in the
      maxillary sinus, and nasal endoscopy showing the maxillary sinus full of polyps.
      The patients were followed and the maxillary sinus was graded endoscopically at
      3, 6 and 12 months after the surgery. Length of surgery, disease recurrence and
      need for revision surgery was documented. RESULTS: Forty-two CFTs and MMA were
      performed in each group. At 6 and 12 months the CFT group demonstrated
      statistically significant improvement in nasal endoscopy scores. Six patients
      recurred by the one year mark in the MMA group, 4 of which underwent revision
      surgery. In the CFT group 2 patients recurred, one who underwent a unilateral
      revision CFT. Furthermore the CFT did not prolong the surgical time and was often
      faster than performing a MMA. CONCLUSION: CFT allows for clearance of all gross
      disease in the maxillary sinus and appears to improve postoperative outcome at 6
      and 12 months and decrease the need for revision surgery.

PMID- 22469613
TI  - Current-oscillator correlation and Fano factor spectrum of quantum shuttle with
      finite bias voltage and temperature.
AB  - A general master equation is derived to describe an electromechanical single-dot
      transistor in the Coulomb blockade regime. In the equation, Fermi distribution
      functions in the two leads are taken into account, which allows one to study the
      system as a function of bias voltage and temperature of the leads. Furthermore,
      we treat the coherent interaction mechanism between electron tunneling events and
      the dynamics of excited vibrational modes. Stationary solutions of the equation
      are numerically calculated. We show that current through the oscillating island
      at low temperature appears to have step-like characteristics as a function of the
      bias voltage and the steps depend on the mean phonon number of the oscillator. At
      higher temperatures the current steps would disappear and this event is
      accompanied by the emergence of thermal noise of the charge transfer. When the
      system is mainly in the ground state, the zero frequency Fano factor of current
      manifests sub-Poissonian noise and when the system is partially driven into its
      excited states it exhibits super-Poissonian noise. The difference in the current
      noise would almost be removed for the situation in which the dissipation rate of
      the oscillator is much larger than the bare tunneling rates of electrons.

PMID- 22469614
TI  - Study of the IMRT interplay effect using a 4DCT Monte Carlo dose calculation.
AB  - Respiratory motion may lead to dose errors when treating thoracic and abdominal
      tumours with radiotherapy. The interplay between complex multileaf collimator
      patterns and patient respiratory motion could result in unintuitive dose changes.
      We have developed a treatment reconstruction simulation computer code that
      accounts for interplay effects by combining multileaf collimator controller log
      files, respiratory trace log files, 4DCT images and a Monte Carlo dose
      calculator. Two three-dimensional (3D) IMRT step-and-shoot plans, a concave
      target and integrated boost were delivered to a 1D rigid motion phantom. Three
      sets of experiments were performed with 100%, 50% and 25% duty cycle gating. The
      log files were collected, and five simulation types were performed on each data
      set: continuous isocentre shift, discrete isocentre shift, 4DCT, 4DCT delivery
      average and 4DCT plan average. Analysis was performed using 3D gamma analysis
      with passing criteria of 2%, 2 mm. The simulation framework was able to
      demonstrate that a single fraction of the integrated boost plan was more
      sensitive to interplay effects than the concave target. Gating was shown to
      reduce the interplay effects. We have developed a 4DCT Monte Carlo simulation
      method that accounts for IMRT interplay effects with respiratory motion by
      utilizing delivery log files.

PMID- 22469615
TI  - The reliability of measurements taken from radiographs in the assessment of
      paediatric flat foot deformity.
AB  - BACKGROUND: Radiographic charted values are widely applied in the assessment of
      paediatric flat foot and as quantitative markers of intervention success. Nearly
      all literature pertaining to the reliability of these measures relates to the
      adult foot. In view of the importance placed on these charted values we assessed
      the inter and intra-rater reliability of 10 key radiographic measures in children
      aged 7-14 years. METHODS: We present the reliability of these measures in terms
      of intra class correlation and standard error based on repeated measures of 50
      radiographs across five independent trained observers. Two new detailed methods
      are presented for the calculation of lateral and dorso-plantar talo-calcaneal
      overlap in an attempt to better define the talo-calcaneal inter-relationship.
      RESULTS: The results demonstrate wide variation of measurement reliability, with
      some measures being highly reproducible and others showing poor reproducibility.
      A strong negative correlation between reliability and the number of steps
      required for the measurement was demonstrated. Consistent with other studies
      intra-rater reliability tended to be higher than that of inter-rater reliability.
      CONCLUSION: In conclusion, we have provided evidence as to which radiographic
      charted measures may be reliably used in evaluating the paediatric flat foot in
      children aged 7-14 years, and which measures are not reliable and we advise
      against their application.

PMID- 22469616
TI  - Circulating  KIT  D816V mutation-positive non-mast cells in peripheral blood are
      characteristic of indolent systemic mastocytosis.
AB  - It is presently accepted that the KIT D816V mutation is detectable in tissues
      with neoplastic mast cells in most patients with indolent systemic mastocytosis.
      In this study, neoplastic mast cells were detected in bone marrow, but not in
      peripheral blood, by flow cytometry in all 25 included cases of indolent systemic
      mastocytosis. However, the KIT D816V mutation was detected using mutation
      specific qPCR in both bone marrow and peripheral blood in all 25 cases,
      demonstrating for the first time that the KIT D816V mutation is consistently
      present in non-mast cells in indolent systemic mastocytosis and that these cells
      are circulating in peripheral blood.

PMID- 22469617
TI  - Anisotropic remastering for reducing feature sizes on UV nanoimprint lithography
      replica molds.
AB  - We present an approach that uses existing nanoimprint molds and reduces  the size
      of the resulting features significantly via a remastering process utilizing the
      anisotropic etchant tetramethylammonium hydroxide and a mold casting step.
      Inverted pyramidal structures and V-grooves were imprinted using these 2.5
      dimensional (2.5D) replica molds. Pattern transfer into silicon (Si) substrates
      was established with an intermediate silicon nitride (SiN(x)) layer that can be
      etched with a much larger selectivity against the imprint resist than the Si
      substrate. The 2.5D resist profiles are thus transferred back into binary
      structures in the SiN(x) layer and subsequently into the Si substrate. A
      substantial size reduction of the diameter of pits from 91 to 33 nm and the width
      of lines from 600 to 142 nm was achieved.

PMID- 22469619
TI  - Differential expression of placental 11beta-hydroxysteroid dehydrogenases in
      pregnant women with diet-treated gestational diabetes mellitus.
AB  - Fetal exposure to excess glucocorticoid is one of the critical factors for the
      fetal origins of adult diseases. However, the mechanism of the local regulation
      of glucocorticoid activity in the human placenta of pregnancies complicated with
      gestational diabetes mellitus (GDM) has not been fully understood. We
      investigated placental 11beta-hydroxysteroid dehydrogenases (11beta-HSDs)
      expression, and analyzed their relationship with cortisol levels in maternal and
      umbilical vein. Pregnant women with GDM after diet intervention (n=23) or normal
      glucose tolerance (NGT, n=22) were studied at the community-based hospital. We
      collected maternal and umbilical venous cord blood and placental tissues from
      both groups. Explanted placentas from NGT were cultured with palmitic acid,
      dexamethasone, insulin or their mixture for 24-h. We examined plasma cortisol,
      cortisone to cortisol ratio, insulin, the homeostasis model assessment of insulin
      resistance index (HOMA-IR) and the insulin secretion index. Quantitative real
      time PCR, Western blot and immunohistochemical assay were applied for the
      measurement of 11beta-HSD1 and 11beta-HSD2 mRNA and protein. GDM had higher
      maternal cortisol levels, HOMA-IR, insulin secretion index and higher cortisone
      to cortisol ratio in umbilical vein. No significant change in cortisol levels in
      umbilical vein and newborn weight was found. GDM placental 11beta-HSD1 levels
      decreased while 11beta-HSD2 increased. Treatment of placenta explants from NGT
      with palmitic acid, dexamethasone, insulin or their combination resulted in a
      significant drop of 11beta-HSD1 and increase in 11beta-HSD2. Differential
      expression of 11beta-HSDs in diet-treated GDM placenta provides a protective
      mechanism for the fetus throughout the adverse environment of pregnancy by
      limiting excessive exposure of the fetus to glucocorticoid.

PMID- 22469618
TI  - Molecular imaging for personalized cancer care.
AB  - Molecular imaging is rapidly gaining recognition as a tool with the capacity to
      improve every facet of cancer care. Molecular imaging in oncology can be defined
      as in vivo characterization and measurement of the key biomolecules and
      molecularly based events that are fundamental to the malignant state. This
      article outlines the basic principles of molecular imaging as applied in oncology
      with both established and emerging techniques. It provides examples of the
      advantages that current molecular imaging techniques offer for improving clinical
      cancer care as well as drug development. It also discusses the importance of
      molecular imaging for the emerging field of theranostics and offers a vision of
      how molecular imaging may one day be integrated with other diagnostic techniques
      to dramatically increase the efficiency and effectiveness of cancer care.

PMID- 22469620
TI  - Tribute to Pierre Mauvais-Jarvis, M.D. 1929-2012. A pioneer in the percutaneous
      delivery of steroid hormones.

PMID- 22469621
TI  - Chronic sympathetic attenuation and energy metabolism in autonomic failure.
AB  - The sympathetic nervous system regulates thermogenesis and energy homeostasis in
      humans. When activated it increases energy expenditure, particularly resting
      energy expenditure. Most human studies used acute infusion of beta-blockers as a
      model to eliminate sympathetic stimulation and to examine the contribution of the
      sympathetic nervous system to energy metabolism and balance. Clinically, however,
      it is also important to assess the effect of chronic sympathetic attenuation on
      energy metabolism. In this context, we hypothesized that resting energy
      expenditure is decreased in patients with autonomic failure who, by definition,
      have low sympathetic tone. We measured 24-hour energy expenditure using whole
      room indirect calorimeter in 10 adults with chronic autonomic failure (6 women;
      age, 64.9+/-9.1 years; body mass index, 25.2+/-4.4 kg/m(2)) and 15 sedentary
      healthy controls of similar age and body composition (8 women; age, 63.1+/-4.0
      years; body mass index, 24.4+/-3.9 kg/m(2)). In 4 patients, we eliminated
      residual sympathetic activity with the ganglionic blocker trimethaphan. We found
      that, after adjusting for body composition, resting energy expenditure did not
      differ between patients with autonomic failure and healthy controls. However,
      resting energy expenditure significantly decreased when residual sympathetic
      activity was eliminated. Our findings suggest that sympathetic tonic support of
      resting energy expenditure is preserved, at least in part, in pathophysiological
      models of chronic sympathetic attenuation.

PMID- 22469622
TI  - Neutrophil gelatinase-associated lipocalin is a novel mineralocorticoid target in
      the cardiovascular system.
AB  - Mineralocorticoid receptor (MR) activation may be deleterious to the
      cardiovascular system, and MR antagonists improve morbidity and mortality of
      patients with heart failure. However, mineralocorticoid signaling in the heart
      remains largely unknown. Using a pan-genomic transcriptomic analysis, we
      identified neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) as a
      strongly induced gene in the heart of mice with conditional and targeted MR
      overexpression in cardiomyocytes (whereas induction was low in glucocorticoid
      receptor-overexpressing mice). NGAL mRNA levels were enhanced after hormonal
      stimulation by the MR ligand aldosterone in cultured cardiac cells and in the
      heart of wild-type mice. Mineralocorticoid pathological challenge induced by
      nephrectomy/aldosterone/salt treatment upregulated NGAL expression in the heart
      and aorta and its plasma levels. We show evidence for MR binding to an NGAL
      promoter, providing a mechanism for NGAL regulation. We propose that NGAL may be
      a marker of mineralocorticoid-dependent injury in the cardiovascular system in
      mice.

PMID- 22469623
TI  - Pseudohypertension.

PMID- 22469624
TI  - A cross-talk between brain-damage patients and infants on action and language.
AB  - Sensorimotor representations in the brain encode the sensory and motor aspects of
      one's own bodily activity. It is highly debated whether sensorimotor
      representations are the core basis for the representation of action-related
      knowledge and, in particular, action words, such as verbs. In this review, we
      will address this question by bringing to bear insights from the study of brain
      damaged patients exhibiting language disorders and from the study of the
      mechanisms for language acquisition in infants. Cognitive neuropsychology studies
      have assessed how damage to representations supporting action production impacts
      patients' ability to process action-related words. While correlations between
      verbal and nonverbal (motor) impairments are very common in patients, damage to
      the representations for action production can leave the ability to understand
      action-words unaffected; likewise, actions can still be produced successfully in
      cases of impaired action-word understanding. Studies with infants have evaluated
      the relevance of sensorimotor information when infants learn to map a novel word
      onto an action that they are performing or perceiving. These results demonstrate
      that sensorimotor information is insufficient to fully account for the complexity
      of verb learning: in this process, infants seem to privilege abstract constructs
      such as goal, intentionality and causality, as well as syntactic constraints,
      over the perceptual and motor dimensions of an action. Altogether, the empirical
      data suggest that, while not crucial for verb learning and understanding,
      sensorimotor processes can contribute to solving the problem of symbol grounding
      and/or serve as a primary mechanism in social cognition, to learn about others'
      goals and intentions. By assessing the relevance of sensorimotor representations
      in the way action-related words are acquired and represented, we aim to provide a
      useful set of criteria for testing specific predictions made by different
      theories of concepts.

PMID- 22469625
TI  - Shifting mountains of electronic waste.

PMID- 22469626
TI  - alpha-Synuclein knockout mice have cognitive impairments.
AB  - alpha-Synuclein is a member of the synuclein family of cytoplasmic, predominantly
      neuron-specific proteins. Considerable amount of alpha-synuclein is found in
      axons and presynaptic terminals of neurons located in brain areas responsible for
      emotions and memory. In the present study we have carried out behavioral
      evaluation of spatial and working long-term memory of alpha-synuclein knockout
      mice. Our data shows that alpha-synuclein knockout mice have reduced learning
      ability in tests requiring both working and spatial memory. For the first time we
      have demonstrated that alpha-synuclein is necessary for these types of learning.

PMID- 22469627
TI  - Biperiden (M1 antagonist) impairs the expression of cocaine conditioned place
      preference but potentiates the expression of cocaine-induced behavioral
      sensitization.
AB  - Cocaine addiction is a public health issue in many countries, stressing the need
      for more effective treatments. As all drugs of abuse, cocaine acts on the brain
      reward system, increasing dopamine (DA) levels. Other neurotransmitters such as
      acetylcholine (ACh) are involved in the mechanisms underlying the development and
      the maintenance of cocaine addiction. ACh plays an important role in learning and
      memory processes and also regulates DA in some specific regions of the central
      nervous system. The present study investigated the effects of biperiden, a
      muscarinic cholinergic (mACh) antagonist in two animal models: conditioned place
      preference (CPP) and behavioral sensitization. Male C57BL/6J mice were used in
      both studies. The CPP protocol was unbiased and carried out in three phases:
      habituation, conditioning and testing. For conditioning, cocaine was injected at
      a dose of 10mg/kg in eight 15 min-sessions. The treatment with biperiden (doses
      of 0.1, 1 and 10 mg/kg) was made 30 min prior to the testing session. For
      behavioral sensitization development, cocaine was administered at the dose of 10
      mg/kg for 10 days. After sensitization, two challenges were performed: saline and
      cocaine (5 mg/kg). Biperiden (10 mg/kg) was administered 30 min before the
      cocaine challenge. At the dose of 10 mg/kg, biperiden blocked the cocaine-CPP
      expression, suggesting an effect on conditioned memory retrieval. However, the
      same dose potentiated the expression of behavioral sensitization, suggesting an
      increase in DA release, probably in the NAc. Biperiden, as other mACh
      antagonists, may be a promising drug for the pharmacologic treatment of cocaine
      addiction.

PMID- 22469628
TI  - Zebrafish (Danio rerio) responds to images animated by mathematical models of
      animal grouping.
AB  - Mathematical models of fish schooling offer powerful tools to understand and
      interpret fundamental aspects of social life, such as foraging, predator
      avoidance, and migration. Here, we study zebrafish (Danio rerio) response to
      computer-animated fish shoals whose motion is generated by a mathematical model
      of schooling. We use a dichotomous test wherein fish freely position themselves
      near static images of zebrafish shoals or images animated by the model whose
      parameters are systematically varied.

PMID- 22469629
TI  - (18)F-FDG cell labeling may underestimate transplanted cell homing: more
      accurate, efficient, and stable cell labeling with hexadecyl-4
      [(18)F]fluorobenzoate for in vivo tracking of transplanted human progenitor cells
      by positron emission tomography.
AB  - Cell therapy is expected to restore perfusion and improve function in the
      ischemic/infarcted myocardium; however, the biological mechanisms and local
      effects of transplanted cells remain unclear. To assess cell fate in vivo,
      hexadecyl-4-[(18)F]fluorobenzoate ((18)F-HFB)  cell labeling was evaluated for
      tracking human circulating progenitor cells (CPCs) with positron emission
      tomography (PET) and was compared to the commonly used 2-[(18)F]fluoro-2-deoxy-d
      glucose ((18)F-FDG) labeling method in a rat myocardial infarction model. CPCs
      were labeled  with 18F-HFB or (18)F-FDG ex vivo under the same conditions. (18)F
      HFB cell-labeling efficiency (23.4 +/- 7.5%) and stability (4 h, 88.4 +/- 6.0%)
      were superior to (18)F-FDG (7.6 +/- 4.1% and 26.6 +/- 6.1%, respectively; p <
      0.05). Neither  labeling approach significantly altered cell viability, phenotype
      or migration potential up to 24 h postlabeling. Two weeks after left anterior
      descending coronary artery ligation, rats received echo-guided intramyocardial
      injection in the infarct border zone with (18)F-HFB-CPCs,  (18)F-FDG-CPCs, (18)F
      HFB, or (18)F-FDG. Dynamic PET imaging of both (18)F-HFB-CPCs and(18)F-FDG-CPCs
      demonstrated that only 16-37% of the initial injection dose (ID) was retained in
      the injection site at 10 min postdelivery, and remaining  activity fell
      significantly over the first 4 h posttransplantation. The (18)F-HFB-CPC signal in
      the target area at 2 h (23.7 +/- 14.7% ID/g) and 4 h (17.6 +/- 13.3% ID/g)
      postinjection was greater than that of (18)F-FDG-CPCs (5.4 +/- 2.3% ID/g and 2.6
      +/-  0.7% ID/g, respectively;p < 0.05). Tissue biodistribution confirmed the
      higher radioactivity in the border zone of (18)F-HFB-CPC rats. Immunostaining of
      heart tissue sections revealed no significant difference in cell retention
      between two labeled cell transplantation groups.  Good correlation with
      biodistribution results was observed in the (18)F-HFB-CPC rats (r = 0.81, p <
      0.05). Compared to (18)F-FDG, labeling human CPCs with(18)F-HFB provides a more
      efficient, stable, and accurate way to quantify the distribution of transplanted 
      cells. (18)F-HFB cell labeling with PET imaging offers a better modality to
      enhance our understanding of early retention, homing, and engraftment with
      cardiac cell therapy.

PMID- 22469630
TI  - Improved solubility of replication factor C (RFC) Walker A mutants.
AB  - Protein insolubility often poses a significant problem during purification
      protocols and in enzyme assays, especially for eukaryotic proteins expressed in a
      recombinant bacterial system. The limited solubility of replication factor C
      (RFC), the clamp loader complex from Saccharomyces cerevisiae, has been
      previously documented. We found that mutant forms of RFC harboring a single point
      mutation in the Walker A motif were even less soluble than the wild-type complex.
      The addition of maltose at 0.75 M to the storage and assay buffers greatly
      increases protein solubility and prevents the complex from falling apart. Our
      analysis of the clamp loading reaction is dependent on fluorescence-based assays,
      which are environmentally sensitive. Using wt RFC as a control, we show that the
      addition of maltose to the reaction buffers does not affect fluorophore responses
      in the assays or the enzyme activity, indicating that maltose can be used as a
      buffer additive for further downstream analysis of these mutants.

PMID- 22469631
TI  - Shiga toxin-producing Escherichia coli serotype O78:H(-) in family, Finland,
      2009.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a pathogen that causes
      gastroenteritis and bloody diarrhea but can lead to severe disease, such as
      hemolytic uremic syndrome (HUS). STEC serotype O78:H(-) is rare among humans, and
      infections are often asymptomatic. We detected a sorbitol-fermenting STEC O78:H(
      ):stx(1c):hlyA in blood and fecal samples of a 2-week-old boy who had bacteremia
      and HUS and in fecal samples of his asymptomatic family members. The phenotypic
      and genotypic characteristics and the virulence properties of this invasive STEC
      were investigated. Our findings demonstrate that contrary to earlier suggestions,
      STEC under certain conditions can invade the human bloodstream. Moreover, this
      study highlights the need to implement appropriate diagnostic methods for
      identifying the whole spectrum of STEC strains associated with HUS.

PMID- 22469633
TI  - Impact of tacrolimus on bone metabolism after kidney transplantation.
AB  - Bone disease is a common clinical problem after kidney transplantation. To date,
      studies investigating the effects of tacrolimus (TAC) on bone metabolism in vivo
      or vitro yielded conflicting data. This study was carried out to discuss the
      relationship between TAC blood concentrations and bone metabolism status in
      kidney transplant recipients. 72 kidney recipients whose time since
      transplantation more than 5 months (5-51 months) were divided into two groups by
      the TAC blood concentrations, high TAC group (TAC>=6 ng/mL) and low TAC
      group(TAC<6 ng/mL), respectively. Bone mineral density (BMD) of lumbar vertebrae
      L1-L4 and neck of the femur and allied biochemical markers (TRAP-5b, B-ALP, 25
      (OH)D, PTH, beta-CrossLaps, N-MID Osteocalcin, Ca, PO4) were measured
      simultaneously. Our results showed that 27.78% of our patients had bone loss and
      the loss rates were statistical different between the high TAC group and low TAC
      group in kidney recipients (45.5% vs 20.0%, P=0.026). Correlation analysis showed
      that TAC concentrations were positively correlated with tartrate-resistant acid
      phosphatase-5b (TRAP-5b) in male recipients (r=0.287, P<0.05). In conclusion,
      kidney transplant recipients with high TAC blood concentrations are at risk of
      bone loss, and TAC may cause bone disorders involved in accelerated bone
      resorption.

PMID- 22469634
TI  - A new reliable bioassay for determining the biological activity of human
      interleukin-12 by using human NK cell line NKG cells.
AB  - A specific and accurate bioassay for determining the biological activity of human
      interleukin-12 (hIL-12), an important typical Th1 cytokine in both innate and
      adaptive immunity, is extensively required for biomedical and clinical study. In
      this paper, we used a new established NK cell line NKG cells as the responder to
      hIL-12 stimulation by detecting their IFN-gamma production. It was found that NKG
      cells produced high level of IFN-gamma when simulated by hIL-12, and the dose
      response curve became the best Sigmoid curve (R(2)=0.9977, p<0.0001) when
      stimulated for 24h. The intra-assay CVs (<10%) and inter-assay CVs (<5%)
      demonstrated that the bioassay was precise and reproducible. Furthermore, no
      obvious cross-effects of other cytokines such as IL-2 and IL-18 was observed on
      the bioassay. Addition of the neutralizing anti-hIL-12 antibody to the bioassay
      significantly inhibited the IFN-gamma production in a dose dependent manner,
      indicating that the bioactivity was actually mediated by hIL-12. The bioassay by
      using NKG cells was also suitable for determining the biological activity of
      recombinant hIL-12 in the form of purified product or culture supernatant by CHO
      hIL-12 cell line. In conclusion, a reliable hIL-12 bioassay for determining its
      biological activity was established by using NKG cells as a responder and
      measuring their production of IFN-gamma.

PMID- 22469635
TI  - Chirality effect in disordered graphene ribbon junctions.
AB  - We investigate the influence of edge chirality on the electronic transport in
      clean or disordered graphene ribbon junctions. By using the tight-binding model
      and the Landauer-Buttiker formalism, the junction conductance is obtained. In the
      clean sample, the zero-magnetic-field junction conductance is strongly chirality
      dependent in both unipolar and bipolar ribbons, whereas the high-magnetic-field
      conductance is either chirality-independent in the unipolar or chirality
      dependent in the bipolar ribbon. Furthermore, we study the disordered sample in
      the presence of magnetic field and find that the junction conductance is always
      chirality-insensitive for both unipolar and bipolar ribbons with adequate
      disorders. In addition, the disorder-induced conductance plateaus can exist in
      all chiral bipolar ribbons provided the disorder strength is moderate. These
      results suggest that we can neglect the effect of edge chirality in fabricating
      electronic devices based on the magnetotransport in a disordered graphene ribbon.

PMID- 22469636
TI  - Increased serum levels of HSP27 as a marker for incipient chronic obstructive
      pulmonary disease in young smokers.
AB  - BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is amongst the
      leading causes of morbidity and mortality, no biomarkers for its early detection
      are known. We have recently demonstrated that COPD is accompanied by elevated
      serum heat shock protein (HSP) 27 levels as compared to a control population.
      OBJECTIVES: In an open prospective study, we investigated whether elevated HSP27
      levels are associated with the early radiological signs of COPD, i.e., air
      trapping (AT), emphysema (E) and impaired lung function. METHODS: In total, 120
      apparently healthy smokers underwent lung function testing and serum sampling.
      Serum levels of HSP27, phospho-HSP27, CXCR2 chemokines and proteins related to
      inflammation, tissue remodeling and apoptosis were evaluated by ELISA. Of these
      120 subjects, 94 voluntarily underwent a high-resolution computed tomography
      scan. RESULTS: AT or AT and E were detected in 57.45%. Subjects with AT and E (n
      = 23) showed significantly higher HSP27 levels than those without any pathology
      [i.e., nothing abnormal detected (NAD)] (4,618 +/- 1,677 vs. 3,282 +/- 1,607
      pg/ml; p = 0.0081). In a univariate logistic regression model including NAD and
      AT and E, the area under the curve of HSP27 in the receiver-operating
      characteristic curve was 0.724, (0.594-0.854, 95% CI; p = 0.0033). Interestingly,
      proinflammatory IL-8 was elevated in those subjects with evidence of AT and E
      compared to those with AT and NAD. Lung function did not correlate with increased
      HSP27 levels or pathological radiological findings. CONCLUSIONS: HSP27 serum
      levels correlated with the early radiological signs of COPD, whereas lung
      function did not match with radiological findings or HSP27 serum levels. Serum
      HSP27 levels may serve as a potential marker to identify the early signs of COPD
      independent of lung function in young smokers.

PMID- 22469637
TI  - Improved quality of life, working ability, and patient satisfaction after a
      pretreatment multimodal assessment method in patients with mixed chronic muscular
      pain: a randomized-controlled study.
AB  - OBJECTIVE: To investigate whether a pretreatment multimodal (MM) assessment of
      patients with chronic muscular pain has an impact on treatment outcome. METHODS:
      The present randomized-controlled study evaluated an MM assessment compared with
      routine multidisciplinary assessment given to a control group. The study
      population consisted of primary care patients with mixed chronic muscular pain.
      Variables assessed were: pain intensity, depression, life stress, quality of life
      (QOL), disability, working ability, and treatment satisfaction. Follow-up was
      performed at 15 months and 182 patients of 220 (83%) completed the study.
      RESULTS: Univariate and multivariate logistic regression showed from baseline to
      15 months a significant improvement in QOL as measured by Short-Form 36 in the MM
      group compared with the control group on the domains of physical function (odds
      ratio 2.40; 95% confidence interval 1.32-4.37), role physical (2.37; 1.10-5.09),
      and role emotional (2.05; 1.05-3.96). Working ability improved more significantly
      in the MM group (46% vs. 35%) and impairment was less (1% vs. 15%) compared with
      the control group (P=0.016). Satisfaction with the assessment was, on average,
      higher (P<0.001) in the MM group than in the control group. DISCUSSION: Patients
      who underwent an MM assessment before treatment in comparison with patients
      receiving routine multidisciplinary assessment improved QOL, working ability, and
      were also significantly more satisfied. This result indicates that MM
      pretreatment assessment could be advantageous in the selection of patients for
      suitable rehabilitation treatment in a primary care setting, and also be used to
      prepare patients for future rehabilitation.

PMID- 22469638
TI  - Interaction of fentanyl and buprenorphine in an experimental model of pain and
      central sensitization in human volunteers.
AB  - OBJECTIVES: : There is controversy about combining opioids with different
      receptor affinities. We assessed the analgesic and antihyperalgesic effects of
      the MU-agonist fentanyl and the partial MU-agonist/kappa-antagonist buprenorphine
      in a human pain model, when given alone or in combination. METHODS: : Fifteen
      healthy male volunteers (22 to 35 y) were included in this randomized, double
      blind, placebo-controlled, cross-over study. Transcutaneous electrical
      stimulation induced spontaneous acute pain and stable areas of secondary
      hyperalgesia. Pain intensities, measured on a numeric rating scale from 0 to 10,
      and the size of the hyperalgesic areas were assessed before, during, and after an
      intravenous infusion of 1.5 ug/kg fentanyl, 1.5 ug/kg buprenorphine, a
      combination of 0.75 ug/kg fentanyl and buprenorphine each, or saline 0.9%.
      Maximum effects of the treatments were compared by repeated measurement analysis
      of variance, and pharmacodynamic interaction models were fitted to the data.
      RESULTS: : Starting from a baseline value of numeric rating scale=6, the maximum
      reduction of pain intensity after correction for placebo effects was 43.9 +/-
      22.2% after fentanyl, 35.0 +/- 23.0% after buprenorphine, and 39.4 +/- 20.8%
      after the combination (mean +/- SD, P=0.24). The maximum reduction of the
      hyperalgesic area was 38.3 +/- 39.0% for fentanyl, 34.4 +/- 32.7% for
      buprenorphine, and 30.0 +/- 53.8% for the combination (mean +/- SD, P=0.82). The
      time courses were best described by pharmacodynamic models assuming an additive
      interaction. DISCUSSION: : For the doses administered in this study,
      buprenorphine and fentanyl showed an additive interaction.

PMID- 22469639
TI  - Cardiovascular disease and nonalcoholic fatty liver disease: does histologic
      severity matter?
AB  - GOALS: We aimed to investigate the prevalence of cardiovascular disease in
      patients with nonalcoholic steatohepatitis (NASH) versus non-NASH fatty liver.
      BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with an
      increased risk of cardiovascular disease, which is a leading cause of death in
      this patient population. NASH is a subset of NAFLD that carries a higher risk of
      progression to cirrhosis and its associated complications. STUDY: We conducted a
      retrospective chart review of patients with biopsy-confirmed NAFLD, including
      NASH and non-NASH fatty liver, within the Gastroenterology and Hepatology clinic
      at Brooke Army Medical Center. Patients with secondary causes of chronic liver
      disease were excluded. The patients' records were reviewed for the presence of
      significant cardiovascular disease, which was defined as a history of stroke,
      unstable angina, myocardial infarction, congestive heart failure, or need for
      revascularization. RESULTS: Nine hundred thirteen patients were identified and
      377 patients met inclusion and exclusion criteria and were included in the final
      analysis. Of these, 219 patients had biopsies showing the presence of at least
      grade I NASH. The overall prevalence of cardiovascular disease was 6.63%. After
      controlling for age, sex, body mass index, and the presence of diabetes, there
      was no significant increase in the prevalence of cardiovascular disease in the
      NASH cohort over the non-NASH group. CONCLUSIONS: Cardiovascular disease is
      common among patients with NAFLD. However, no increased risk of cardiovascular
      disease was found among those patients with NASH as compared with those with non
      NASH fatty liver.

PMID- 22469640
TI  - The role of nutrients in the development, progression, and treatment of
      nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver
      disease in adults and children and is currently the third most common indication
      for liver transplantation in North America. Its pathogenesis is thought to be
      secondary to multiple "hits" derived from the dietary components, adipose tissue,
      immune system, and intestinal microbiota. Lack of physical activity may
      contribute as well. Nutrients may exert their effect directly or through
      alteration of the intestinal microbiota. Research focusing on specific dietary
      components predisposing to NAFLD has shown conflicting results. Total energy
      intake, and macronutrients, has been linked to the development of NAFLD. Fructose
      not only contributes to hepatic steatosis but may trigger inflammatory signals as
      well. Polyunsaturated fatty acids are thought to exert anti-inflammatory effects.
      The role of vitamins as well as minerals in this field is actively being
      investigated. In this review, we discuss the evidence-linking macronutrients
      (such as carbohydrates and fat in general and fructose, fiber, short chain fatty
      acids, polyunsaturated fatty, and choline specifically) and micronutrients (such
      as vitamin E and C and minerals) with the development and treatment of NAFLD. We
      also discuss the literature on physical activity and NAFLD.

PMID- 22469641
TI  - Motility disorders of the upper gastrointestinal tract in the intensive care
      unit: pathophysiology and contemporary management.
AB  - Upper gastrointestinal (GI) dysmotility, an entity commonly found in the
      intensive care unit setting, can lead to insufficient nutrient intake while
      increasing the risk of infection and mortality. Further, overcoming the altered
      motility with early enteral feeding is associated with a reduced incidence of
      infectious complications in intensive care unit patients. Upper GI dysmotility in
      critical care patients is a common occurrence, and there are many causes for this
      problem, which affects a very heterogenous population with a multitude of
      underlying medical abnormalities. Therefore, it is of utmost importance to
      identify this widespread problem and subsequently institute a proper therapy as
      rapidly as possible. Prokinetic pharmacotherapies are currently the mainstay for
      the management of disordered upper GI motility. Future therapies, aimed at the
      underlying pathophysiology of this complex problem, are under investigation.
      These aim is to reduce the side effects of the currently available options, while
      improving on nutrition delivery in the critically ill. This review discusses the
      pathophysiology, clinical manifestations, diagnosis, and treatment of upper GI
      motility disturbances in the critically ill.

PMID- 22469647
TI  - Enhanced alpha-ketoglutaric acid production in Yarrowia lipolytica WSH-Z06 by an
      improved integrated fed-batch strategy.
AB  - This study aimed at enhancing alpha-ketoglutaric acid (alpha-KG) production by
      Yarrowia lipolytica WSH-Z06. Batch culture experiments demonstrated that CaCO(3)
      and a relatively low pH (3.0) in the alpha-KG production phase contributed to
      alpha-KG synthesis. Using a two-stage pH control strategy, in which pH was
      buffered by CaCO(3) in the growth phase and then maintained at 3.0 in the alpha
      KG production phase, the yield of alpha-KG reached 53.4 g L(-1). In the later
      phase of batch fermentation, the glycerol was exhausted but synthesis of alpha-KG
      did not cease. Therefore, glycerol was fed with an integrated fed-batch mode, and
      alpha-KG production increased to 66.2 g L(-1) with a productivity of 0.35 g L(-1)
      h(-1). Compared to optimal batch culture, alpha-KG production and productivity
      were enhanced by 23.9% and 16.7%, respectively. The two-stage pH control
      strategy, constant feeding approach and lower pH in later phase would be useful
      for alpha-KG industrial production.

PMID- 22469648
TI  - Reinforcer devaluation by extinction depends on the food restriction protocol.
AB  - A common feature of reinforcer devaluation studies is that new learning induces
      the devaluation. The present study used extinction to induce new learning about
      the conditioned reinforcer in a heterogeneous chain schedule. Rats pressed a
      lever in a heterogeneous chain schedule to produce a conditioned reinforcer
      (light) associated with the opportunity to obtain an unconditioned reinforcer
      (food) by pulling a chain. The density of food reinforcement correlated with the
      conditioned reinforcer was varied in a comparison of continuous and variable
      ratio reinforcement schedules of chain pulling; this had no noticeable effect on
      conditioned reinforcer devaluation produced by extinction of chain pulling. In
      contrast, how rats were deprived appeared to matter very much. Restricting meal
      duration to 1h daily produced more lever pressing during baseline training and a
      greater reductive effect of devaluation on lever pressing than restricting body
      weight to 80% of a control rat's weight, which eliminated the devaluation effect.
      Further analysis suggested that meal-duration restriction may have produced
      devaluation effects because it was more effective than weight restriction in
      reducing rats' body weights. Our results exposed an important limitation on the
      devaluation of conditioned reinforcers: slight differences in food restriction,
      using two commonly employed food-restriction procedures, can produce completely
      different interpretations of reinforcer devaluation while leaving reinforcer
      based learning intact.

PMID- 22469649
TI  - Low-dose sublingual zolpidem (Intermezzo) for insomnia due to middle-of-the-night
      awakening.

PMID- 22469650
TI  - Bupivacaine liposomal injection (Exparel) for post surgical pain.

PMID- 22469651
TI  - Ruxolitinib (Jakafi) for myelofibrosis.

PMID- 22469652
TI  - Patterned graphone--a novel template for molecular packing.
AB  - Precise positioning and packing of nanoscale building blocks is essential for the
      fabrication of many nanoelectro-mechanical devices. Carrying out such
      manipulations at the nanoscale still remains a challenge. Here we propose the use
      of graphone domain arrays embedded in a graphene sheet as a template to precisely
      position and pack molecules. Our atomistic simulations show that a graphone
      domain is able to adopt well-defined three-dimensional geometries, which in turn
      create 'energy wells' to trap molecules by means of physisorption. Using the C60
      molecule as a model block, the stable trapping conditions are identified. The
      present work presents a novel route to position and pack molecules for
      nanoengineering applications.

PMID- 22469653
TI  - Parallel and patterned optogenetic manipulation of neurons in the brain slice
      using a DMD-based projector.
AB  - Optical manipulation technologies greatly advanced the understanding of the
      neuronal network and its dysfunctions. To achieve patterned and parallel optical
      switching, we developed a microscopic illumination system using a commercial DMD
      based projector and a software program. The spatiotemporal patterning of the
      system was evaluated using acute slices of the hippocampus. The neural activity
      was optically manipulated, positively by the combination of channelrhodopsin-2
      (ChR2) and blue light, and negatively by the combination of archaerhodopsin-T
      (ArchT) and green light. It is suggested that our projector-managing optical
      system (PMOS) would effectively facilitate the optogenetic analyses of neurons
      and their circuits.

PMID- 22469654
TI  - Aconitum alkaloid content and the high toxicity of aconite tincture.
AB  - Although proprietary medicines and decoction of processed aconite roots are the
      most widely used, tincture accounts for the great majority of aconite poisoning
      cases in China, indicating that it is much more toxic than other formulations.
      Aconite tincture is often self-prepared at home and raw aconite plants or roots
      are often used. Even if processed aconite roots were used to make the tincture,
      the amount of Aconitum alkaloids is highly variable, depending on the adequacy of
      processing and quality control. Aconitum alkaloids dissolve efficiently in
      alcohol. For these reasons, tincture contains very high concentrations of
      Aconitum alkaloids. Despite its high intrinsic toxicity, overdose of aconite
      tincture by the users has been common. Severe aconite poisoning can be
      complicated by fatal ventricular tachyarrhythmias and asystole. The public should
      be repeatedly warned of the danger of taking aconite tincture by mouth.

PMID- 22469655
TI  - Commentary on "3D bloodstain pattern analysis: ballistic reconstruction of the
      trajectories of blood drops and determination of the centres of origin of the
      bloodstains" by Buck et al. [Forensic Sci. Int. 206 (2011) 22-28].

PMID- 22469656
TI  - Chitosan oligosaccharide inhibits LPS-induced apoptosis of vascular endothelial
      cells through the BKCa channel and the p38 signaling pathway.
AB  - Lipopolysaccharide (LPS) can cause injuries to the vascular endothelium and
      induce cell apoptosis resulting in various vascular diseases. However, the
      relevant processes and molecular mechanisms have not yet been fully clarified.
      Chitosan oligosaccharide (COS) can protect cells, but there are only a few
      reports showing that it can effectively inhibit LPS-induced cell apoptosis. This
      study focuses on human umbilical vein endothelial cells (HUVECs). After cells
      were treated with LPS for 4-8 h, it was found by flow cytometry that the cell
      apoptosis ratio, and the reactive oxygen species and calcium concentration in the
      cells increased. Furthermore, using the patch clamp technique, it was observed
      that the large conductance calcium-activated potassium channel (BKCa) was
      activated at the same time. All phenomena could be reversed after pretreatment
      with COS for 24 h, showing that COS is capable of inhibiting LPS-induced cell
      apoptosis. The results of the assays on the action mechanism of COS show that it
      is capable of inhibiting the LPS-induced decrease of the Bcl-2/Bax ratio,
      increase of caspase-3 and activation of BKCa. Thus, one of the mechanisms of
      action of COS in the inhibition of cell apoptosis is to participate in the
      regulation of the BKCa channel. On the other hand, COS can inhibit the
      phosphorylation of LPS-induced p38 and accelerate the expression of O-GlcNAc
      glycosyltransferase, which indicates that COS can inhibit LPS-induced cell
      apoptosis through many pathways.

PMID- 22469657
TI  - Genomic structure, molecular characterization and functional analysis of Pekin
      duck interleukin-10.
AB  - Here we describe the cloning and expression of Pekin duck IL-10 (duIL-10) and a
      six exon-5 intron structure of an IL-10 gene. Two transcripts encoding duIL-10
      with an alternatively spliced 3'UTR, and a transcript lacking exon 5 with a novel
      coding sequence for its C-terminus (duIL-10DeltaE5) were isolated from
      splenocytes. The duIL-10 protein has an amino acid identity of 79% and 47% with
      chicken and human IL-10, respectively. The duck IL-10 gene shares a similar
      structure of the respective exons 1-5 with the IL-10 genes of other vertebrates
      but has an alternative exon. The duIL-10 3D structure by homology modeling was
      similar to that of the human IL-10 monomer, whereas the predicted duIL-10DeltaE5
      protein lacks helix F. DuIL-10 and duIL-10DeltaE5 transcripts were most abundant
      in primary and secondary immune organs and lung. Recombinant duIL-10 suppressed
      duck IL-2 transcripts in mitogen-activated PBMCs. Our observation suggests
      evolutionary conservation of structure and function of the duIL-10 protein but
      the roles of the novel IL-10 splice variants in the regulation of duck immune
      responses and evolution of vertebrate immunity remain to be elucidated.

PMID- 22469658
TI  - Teleost IL-6 promotes antibody production through STAT3 signaling via IL-6R and
      gp130.
AB  - Teleost IL-6 is upregulated after antigen stimulation; therefore, we hypothesized
      that fish IL-6 contributes to antibody production during immune responses against
      infections. To verify this hypothesis, we first cloned IL-6R and gp130 in fugu
      (Takifugu rubripes) in the present study. The membrane and soluble forms of IL-6R
      were identified by the identification of cDNA clones of IL-6R homologues. Three
      STAT3-docking sites were found in the intracellular region of fugu gp130.
      Expression analysis showed that fugu IL-6R and gp130 were expressed in mIgM(+) B
      cells, suggesting that fugu B cells are stimulated by IL-6. Recombinant fugu IL-6
      (rfIL-6) increased the gene expression of secretory antibodies by mIgM(+) B cells
      in vitro. The rfIL-6 and soluble form of rfIL-6R activated STAT3 phosphorylation
      in the B cells and a cultured cell line transfected with fugu gp130. These
      results indicate that fugu IL-6 enhances antibody production in the B-cell
      lineage via gp130 and STAT3 signaling.

PMID- 22469659
TI  - Breakeven, cost benefit, cost effectiveness, and willingness to pay for web-based
      versus face-to-face education delivery for health professionals.
AB  - BACKGROUND: The introduction of Web-based education and open universities has
      seen an increase in access to professional development within the health
      professional education marketplace. Economic efficiencies of Web-based education
      and traditional face-to-face educational approaches have not been compared under
      randomized controlled trial conditions. OBJECTIVE: To compare costs and effects
      of Web-based and face-to-face short courses in falls prevention education for
      health professionals. METHODS: We designed two short courses to improve the
      clinical performance of health professionals in exercise prescription for falls
      prevention. One was developed for delivery in face-to-face mode and the other for
      online learning. Data were collected on learning outcomes including
      participation, satisfaction, knowledge acquisition, and change in practice, and
      combined with costs, savings, and benefits, to enable a break-even analysis from
      the perspective of the provider, cost-effectiveness analysis from the perspective
      of the health service, and cost-benefit analysis from the perspective of the
      participant. RESULTS: Face-to-face and Web-based delivery modalities produced
      comparable outcomes for participation, satisfaction, knowledge acquisition, and
      change in practice. Break-even analysis identified the Web-based educational
      approach to be robustly superior to face-to-face education, requiring a lower
      number of enrollments for the program to reach its break-even point. Cost
      effectiveness analyses from the perspective of the health service and cost
      benefit analysis from the perspective of the participant favored face-to-face
      education, although the outcomes were contingent on the sensitivity analysis
      applied (eg, the fee structure used). CONCLUSIONS: The Web-based educational
      approach was clearly more efficient from the perspective of the education
      provider. In the presence of relatively equivocal results for comparisons from
      other stakeholder perspectives, it is likely that providers would prefer to
      deliver education via a Web-based medium. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry (ACTRN): 12610000135011;
      http://www.anzctr.org.au/trial_view.aspx?id=335135 (Archived by WebCite at
      http://www.webcitation.org/668POww4L).

PMID- 22469660
TI  - Isotopic phonon effects in beta-rhombohedral boron--non-statistical isotope
      distribution.
AB  - On the basis of the spectra of IR- and Raman-active phonons, the isotopic phonon
      effects in beta-rhombohedral boron are analysed for polycrystalline (10)B- and
      (11)B-enriched samples of different origin and high-purity (nat)B single
      crystals. Intra- and inter-icosahedral B-B vibrations are harmonic, hence meeting
      the virtual crystal approximation (VCA) requirements. Deviations from the phonon
      shift expected according to the VCA are attributed to the anharmonic share of the
      lattice vibrations. In the case of icosahedral vibrations, the agreement with
      calculations on alpha-rhombohedral boron by Shirai and Katayama-Yoshida is quite
      satisfactory. Phonon shifts due to isotopic disorder in (nat)B are separated and
      determined. Some phonon frequencies are sensitive to impurities. The isotopic
      phonon effects yield valuable specific information on the nature of the different
      phonon modes. The occupation of regular boron sites by isotopes deviates
      significantly from the random distribution.

PMID- 22469661
TI  - Perfluorinated compounds may lower vaccine protection in children.

PMID- 22469662
TI  - Progressive lung cancer determined by expression profiling and transcriptional
      regulation.
AB  - Clinically, our ability to predict disease outcome for patients with early stage
      lung cancer is currently poor. To address this issue, tumour specimens were
      collected at surgery from non-small cell lung cancer (NSCLC) patients as part of
      the European Early Lung Cancer (EUELC) consortium. The patients were followed-up
      for three years post-surgery and patients who suffered progressive disease (PD,
      tumour recurrence, metastasis or a second primary) or remained disease-free (DF)
      during follow-up were identified. RNA from both tumour and adjacent-normal lung
      tissue was extracted from patients and subjected to microarray expression
      profiling. These samples included 36 adenocarcinomas and 23 squamous cell
      carcinomas from both PD and DF patients. The microarray data was subject to a
      series of systematic bioinformatics analyses at gene, network and transcription
      factor levels. The focus of these analyses was 2-fold: firstly to determine
      whether there were specific biomarkers capable of differentiating between PD and
      DF patients, and secondly, to identify molecular networks which may contribute to
      the progressive tumour phenotype. The experimental design and analyses performed
      permitted the clear differentiation between PD and DF patients using a set of
      biomarkers implicated in neuroendocrine signalling and allowed the inference of a
      set of transcription factors whose activity may differ according to disease
      outcome. Potential links between the biomarkers, the transcription factors and
      the genes p21/CDKN1A and Myc, which have previously been implicated in NSCLC
      development, were revealed by a combination of pathway analysis and microarray
      meta-analysis. These findings suggest that neuroendocrine-related genes,
      potentially driven through p21/CDKN1A and Myc, are closely linked to whether or
      not a NSCLC patient will have poor clinical outcome.

PMID- 22469663
TI  - Identification of a Wnt-induced protein complex by affinity proteomics using an
      antibody that recognizes a sub-population of beta-catenin.
AB  - beta-catenin is a signaling protein with diverse functions in cell adhesion and
      Wnt signaling. Although beta-catenin has been shown to participate in many
      protein-protein interactions, it is not clear which combinations of beta-catenin
      interacting proteins form discrete complexes. We have generated a novel antibody,
      termed 4B3, which recognizes only a small subset of total cellular beta-catenin.
      Affinity proteomics using 4B3, in combination with subcellular fractionation, has
      allowed us to define a discrete trimeric complex of beta-catenin, alpha-catenin
      and the tumor suppressor APC, which forms in the cytoplasm in response to Wnt
      signaling. Depletion of the limiting component of this complex, APC, implicates
      the complex in mediating Wnt-induced changes in cell-cell adhesion. APC is also
      essential for N-terminal phosphorylation of beta-catenin within this complex.
      Each component of beta-catenin/APC/alpha-catenin complex co-exists in other
      protein complexes, thus use of a selective antibody for affinity proteomics has
      allowed us to go beyond the generation of a list of potential beta-catenin
      interacting proteins, and define when and where a specific complex forms.

PMID- 22469664
TI  - Analgesic use in the older person.
AB  - PURPOSE OF REVIEW: To summarize developments in analgesic use in the older
      person. RECENT FINDINGS: Observational studies, reviews and a few randomized
      trials dealing with analgesic use in the older person have been published during
      the past year. Recent trials examine also pharmacological/nonpharmacological
      interventions, and education of older patients as well as clinicians in pain
      management. SUMMARY: Under-treatment of pain remains a major concern in community
      dwelling or institutionalized older persons, especially with dementia. An
      increased awareness of pain and palliative pain management in the older person is
      present throughout the literature. Age-related factors affect the safety and
      efficacy of the analgesic treatment and pharmacological aspects are often
      underlined, especially when impaired cognition and frailty are present. The use
      of topical analgesics, well tolerated in older persons, allows reduction of
      concomitant treatments and of adverse events. Optimizing analgesic use in older
      patients is carried out by exploring motivations and attitudes of the patients,
      by analysing barriers and practices of clinicians and by setting up structured
      educational nursing interventions. Although a larger number of older persons are
      included in studies, prospective and large-scale trials are needed in this
      vulnerable population characterized by a high variability and heterogeneity.

PMID- 22469665
TI  - Dyspnea prevalence, trajectories, and measurement in critical care and at life's
      end.
AB  - PURPOSE OF REVIEW: Dyspnea is a multidimensional response to an asphyxial threat
      that heralds respiratory failure. A clinician's ability to treat dyspnea warrants
      understanding the prevalence, burden, trajectories, and measurement across
      chronic conditions and exacerbations. This review focuses on two contexts: the
      intensive care unit and the near death stage of illness. RECENT FINDINGS: Dyspnea
      is the most distressing symptom experienced by critically ill patients at risk
      for dying. New longitudinal studies reveal varying dyspnea trajectories over time
      and by diagnosis. Patients with noncancer diagnoses, particularly chronic
      obstructive pulmonary disease, experience severe dyspnea for months before death,
      whereas patients with cancer even without apparent cardiorespiratory disease have
      an escalation of dyspnea near death. The sickest patients and those who are
      cognitively impaired or unconscious are not represented because self-report
      measures are used. Thus, dyspnea is underrepresented in most end-of-life cohorts.
      In most data, the Numeric Rating Scale for the intensity of breathlessness, while
      unidimensional, is the most valid measure for palliative care because of its
      simplicity. Use of the Respiratory Distress Observation Scale in future studies
      will permit the inclusion of patients who are unable to self-report dyspnea.
      SUMMARY: In summary, new evidence is demonstrating the high prevalence and
      distress associated with dyspnea among critically ill patients and patients near
      death.

PMID- 22469666
TI  - Understanding cough and its management in lung cancer.
AB  - PURPOSE OF REVIEW: This article summarizes the current understanding of cough in
      lung cancer, strategies for its management and highlights areas where further
      research is warranted.Cough is common, severe and distressing for many lung
      cancer patients. Currently few effective cough interventions exist for lung
      cancer patients. This review proposes some of the mechanisms that may underlie
      cough in lung cancer and presents the existing data on antitussive therapy in
      cancer patients. A greater focus on the cough mechanisms may enable effective
      antitussives to be developed in the future for lung cancer patients. A brief
      overview of the validated cough assessment tools is provided. The use of such
      tools will enable robust clinical endpoints to be determined for future cough
      intervention studies. A 'cough treatment pyramid' is presented to provide a
      pragmatic approach to the management of cough in lung cancer patients. RECENT
      FINDINGS: Despite the small number of publications on cough in lung cancer, some
      recent research has characterized cough for the first time in lung cancer
      patients. Its impact on quality of life domains such as psychological, social and
      physical is significant. The lung cancer symptom cluster of cough, breathlessness
      and fatigue has also been described. A recently developed cough severity
      assessment tool has provided researchers with a short well validated seven-item
      questionnaire to determine this important cough characteristic. In addition, a
      Cochrane Database Systematic Review on Interventions for Cough in Cancer has also
      been published. These studies are all described in the present review.
      Understanding the impact of a symptom such as cough, the assessment of cough and
      its potential underlying mechanisms is crucial if we are to manage this symptom
      effectively. SUMMARY: Current cough management in lung cancer patients is lagging
      behind the management of other cancer symptoms. There is now an increasing need
      to diagnose and treat cough more effectively, as lung cancer patients are living
      longer with chronic symptoms such as cough.

PMID- 22469667
TI  - Spiritual care in a multicultural oncology environment.
AB  - PURPOSE OF REVIEW: Increasingly, oncology is practiced within multicultural
      environments. All aspects of care, including spiritual care should be delivered
      to patients with cancer in a culturally sensitive manner. In this article, we
      discuss the influence of culture on patients with cancer throughout the disease
      process by highlighting relevant reports in the literature. RECENT FINDINGS: Most
      articles focussing on culture and oncology are single-author or single
      institution narrative reports pertaining to experiences with an individual
      racial, ethnic, religious or minority patient group. The majority of articles are
      found within the palliative care and nursing literature. SUMMARY: Health-related
      values vary widely across cultures, and the experience of spiritual care in
      oncology differs greatly across cultural groups. Although culture is generally
      recognized as an important health determinant that impacts the experience of
      care, the extent of different cultural influences is not well understood due to a
      paucity of relevant data, and reports on resources and educational strategies to
      optimize culturally competent spiritual care are similarly lacking.

PMID- 22469668
TI  - Palliative care and spiritual care:  the crucial role of spiritual care in the
      care of patients with advanced illness.
AB  - PURPOSE OF REVIEW: Within the hospice and palliative care movement, patients'
      religion/spirituality (R/S) has been a core component of care incorporated within
      international and US palliative care guidelines. However, as the discipline of
      palliative care has been incorporated into the larger biomedical community, the
      inclusion of spiritual care has become controversial. This review summarizes key
      empirical research at the intersection of palliative care and R/S in order to
      assess its validity as a domain of end-of-life care. RECENT FINDINGS: Recent
      research shows that R/S and spiritual care are important components to the care
      of patients facing advanced illness. Patients - particularly ethnic minorities -
      rely upon R/S as an important means to interpret and cope with illness. Studies
      suggest that R/S plays an important role in coping with disease-related symptoms,
      improves quality of life, and impacts medical decision-making near death.
      Patients largely desire medical caregivers to take an active role in providing
      spiritual care, and patients likewise frequently experience multiple spiritual
      needs arising in the face of life-threatening illness. SUMMARY: Despite an
      empirical evidence for spiritual care as part of palliative care, R/S remains
      insufficiently addressed by the medical system. Further research is required in
      order to more clearly identify the roles of healthcare providers and standardize
      the provision of spiritual care within palliative care.

PMID- 22469669
TI  - A heuristic model of enactive compassion.
AB  - PURPOSE OF REVIEW: This article is an investigation of the possibility that
      compassion is not a discrete feature but an emergent and contingent process that
      is at its base enactive. Compassion must be primed through the cultivation of
      various factors. This article endeavors to identify interdependent components of
      compassion. This is particularly relevant for those in the end-of-life care
      professions, wherein compassion is an essential factor in the care of those
      suffering from a catastrophic illness or injury. The Halifax Model of Compassion
      is presented here as a new vision of compassion with particular relevance for the
      training of compassion in clinicians. RECENT FINDINGS: Compassion is generally
      valued as a prosocial mental quality. The factors that foster compassion are not
      well understood, and the essential components of compassion have not been
      sufficiently delineated. Neuroscience research on compassion has only recently
      begun, and there is little clinical research on the role of compassion in end-of
      life care. SUMMARY: Compassion is in general seen as having two main components:
      the affective feeling of caring for one who is suffering and the motivation to
      relieve suffering. This definition of compassion might impose limitations and
      will, therefore, have consequences on how one trains compassion in clinicians and
      others. It is the author's premise that compassion is dispositionally enactive
      (the interactions between living organisms and their environments, i.e., the
      propensity toward perception-action in relation to one's surrounds), and it is a
      process that is contingent and emergent.

PMID- 22469670
TI  - Update on complex nonpharmacological interventions for breathlessness.
AB  - PURPOSE OF REVIEW: The study provides a review of current evidence about the role
      of complex nonpharmacological strategies in managing the multidimensional
      components of the breathlessness experience for individuals with life-limiting
      conditions. RECENT FINDINGS: Evidence continues to demonstrate the significant
      impact of breathlessness on patients' quality of life, day-to-day activity, and
      physical and psychosocial functioning. Recent evidence also confirms that
      patients draw on a number of self-initiated actions to cope with breathlessness,
      although many do not use strategies that are supported by a growing body of
      evidence from randomized controlled trials. Current literature supports the use
      of multicomponent, nonpharmacological interventions comprising strategies to
      improve breathing efficiency and reducing psychological distress to manage
      breathlessness. However trials of these approaches have mostly been conducted
      among patients with chronic obstructive pulmonary disease (COPD) or lung cancer,
      and few studies have investigated the benefits of nonpharmacological for patients
      in later stages of disease. Further investigation of interventions is required
      across a broader range of chronic life-limiting conditions. Addressing
      breathlessness and its co-occurring symptoms (symptom clusters) is also an area
      for future enquiry. SUMMARY: The experience of breathlessness and strategies
      adopted by patients to manage the experience highlight the importance of
      multidimensional approaches to improve outcomes for patients with life-limiting
      conditions. There is good evidence to support the role of multicomponent,
      nonpharmacological interventions in reducing breathlessness for patients with
      COPD and lung cancer, although further studies are required to understand the
      particular clinical contexts in which such interventions are appropriate.

PMID- 22469671
TI  - Update on combined modalities for the management of breathlessness.
AB  - PURPOSE OF REVIEW: Breathlessness is a symptom which is felt as shortness of
      breath or tightness in the chest. The symptom of breathlessness is essentially an
      awareness of difficult respiration; in other words, respiration becomes an
      effort. The increase due to pathological change supplements the effect of
      exercise. In this article, the combined modalities of palliative management of
      breathlessness are discussed on the basis of current literature (published and
      indexed in PubMed from January 2009 to week 1 in January 2012). The findings were
      used to derive a treatment algorithm for the management of dyspnoea. RECENT
      FINDINGS: The findings in the recently published literature with treatment
      recommendations for the management of breathlessness were scarce. Although there
      are multiple clinical trials regarding treatment of breathlessness, there is a
      paucity of well designed, prospective, randomized controlled trials with large
      enough numbers of patients suffering from breathlessness and treated with
      combined pharmacological and nonpharmacological methods. SUMMARY: As yet, there
      is no clinical trial that can accurately reflect the far-reaching effects of
      combined treatment modalities of breathlessness. Therefore, at present, we would
      recommend combining a treatment with opioids, anxiolytics and corticosteroids
      accompanied by oxygen and physiotherapeutic treatment options.

PMID- 22469673
TI  - Intraoperative neurophysiological monitoring has been employed to protect nervous
      system structures at risk. Introduction.

PMID- 22469674
TI  - Intraoperative use of somatosensory-evoked potential in monitoring nerve roots.
AB  - Different intraoperative neuromonitoring modalities (mixed-nerve somatosensory
      evoked potential [M-SSEP], dermatomal somatosensory-evoked potential [D-SSEP],
      compound motor-evoked potential [CMEP], electromyography [EMG], and the Hoffmann
      reflex [H-reflex]) have been developed for early detection of nerve root injury,
      for timely revision, and for damage reduction. In this study, we discuss the
      advantages and disadvantages of M-SSEP and D-SSEP by reviewing experimental
      evidence from animal models and clinical practice.

PMID- 22469675
TI  - Utility of motor evoked potentials for intraoperative nerve root monitoring.
AB  - There is no entirely satisfactory way to monitor nerve root integrity during
      spinal surgery. In particular, standard free-running electromyography carries a
      high false-positive rate and some false-negative rate of injury. Stimulated
      electromyography to direct root stimulation can only be done intermittently, and
      roots are often inaccessible. This article reviews to what extent muscle motor
      evoked potential (MEP) monitoring might help. It presents background
      considerations, describes MEP methodology, and summarizes relevant experimental
      animal and clinical studies. Based on current evidence, root compromise can cause
      myotomal MEP deterioration that in some cases may be reversible. However, because
      of radicular overlap, limited sampling, confounding factors, and response
      variability, the effects range from no appreciable change to variable degrees of
      amplitude reduction to disappearance and some false-positive and false-negative
      results should be expected. For root monitoring, multichannel MEP recordings
      should span adjacent myotomes and avoid mixed myotome derivations. Only amplitude
      reduction warning criteria have been studied, but no percentage cutoff consensus
      has emerged, and this approach is troubled by response variability. There is some
      evidence that MEPs might reduce false electromyographic results. In conclusion,
      muscle MEPs could compliment electromyography but seem unlikely to completely
      solve the problem of nerve root monitoring.

PMID- 22469676
TI  - Monitoring spinal nerve function with H-reflexes.
AB  - H-reflexes have been used in the clinical neurophysiology laboratory for some
      time to assess patients with neuromuscular disorders. There are only a few
      reports for the application of H-reflexes for intraoperative neurophysiologic
      monitoring. The goals of this article are to review the intraoperative
      neurophysiologic monitoring of spinal nerve root function with H-reflexes. The
      following will be reviewed: (1) Introduction to H-reflexes, (2) pathophysiology
      of spinal nerve root function, (3) neurophysiologic basis of H-reflexes, (4)
      gastrocnemius H-reflex, (5) flexor carpi radialis H-reflex, (6) anesthetic
      technique and research, and (7) intraoperative applications of H-reflexes. H
      reflexes are single sweep real-time recordings that provide immediate feedback to
      the surgeon. They can be used to monitor not only sensory and motor spinal nerve
      root function but also peripheral sensory and motor nerves, plexus, and
      postsynaptic spinal cord gray matter function.

PMID- 22469677
TI  - Utility of electromyography for nerve root monitoring during spinal surgery.
AB  - In addition to potential spinal cord injury, spinal surgery carries a risk of
      damage to spinal nerve roots, which could result in sensory or motor deficit.
      Both spontaneous and triggered electromyography (sEMG and tEMG, respectively)
      have been employed to reduce the risk of these deficits. This article reviews the
      theory and best practice of electromyographic monitoring for spinal surgery, the
      evidence supporting its use for various types of spine surgery, and finally,
      suggestions for future directions to improve knowledge and advance
      electromyographic monitoring of spinal nerves.

PMID- 22469678
TI  - NIOM for spinal deformity surgery: there's more than one way to skin a cat.
AB  - STUDY DESIGN: This was a 23-year retrospective study of 3436 consecutive
      pediatric orthopedic spinal surgery patients between 1995 and 2008. OBJECTIVE: To
      demonstrate the effectiveness of multimodality electrophysiologic monitoring in
      reducing the incidence of iatrogenic neurologic deficit in a pediatric spinal
      surgery population. SUMMARY OF BACKGROUND DATA: The elective nature of many
      pediatric spinal surgery procedures continues to drive the need for minimizing
      risk to each individual patient. Electrophysiologic monitoring has been proposed
      as an effective means of decreasing permanent neurologic injury in this
      population. METHODS: A total of 3436 consecutive monitored pediatric spinal
      procedures at a single institution between January 1985 and September 2008 were
      reviewed. Monitoring included somatosensory evoked potentials, descending
      neurogenic evoked potentials, transcranial electric motor evoked potentials, and
      various nerve root monitoring techniques. Patients were divided into 10
      diagnostic categories. True-positive and false-negative monitoring outcomes were
      analyzed for each category. Neurologic deficits were classified as transient or
      permanent. RESULTS: Seven of 10 diagnostic groups demonstrated true-positive
      findings resulting in surgical intervention. Seventy-four (2.2%) potential
      neurologic deficits were identified in 3436 pediatric surgical cases. Seven
      patients (0.2%) had false-negative monitoring outcomes. These patients awoke with
      neurologic deficits undetected by neuromonitoring. Intervention reduced permanent
      neurologic deficits to 6 (0.17%) patients. Monitoring data were able to detect
      permanent neurologic status in 99.6% of this population. The ratio of
      intraoperative events to total monitored cases was 1 event every 42 surgical
      cases and 1 permanent neurologic deficit every 573 cases. CONCLUSIONS: The
      combined use of somatosensory evoked potentials, transcranial electric motor
      evoked potentials, descending neurogenic evoked potentials, and electromyography
      monitoring allowed accurate detection of permanent neurologic status in 99.6% of
      3436 patients and reduced the total number of permanent neurologic injuries to 6.

PMID- 22469679
TI  - Intraoperative neuromonitoring during glioma surgery:  bring in the expert
      neurophysiologists!
AB  - BACKGROUND: Resection of gliomas in or adjacent to the motor system is widely
      performed using intraoperative neuromonitoring (IOM). Despite the fact that data
      on the safety of IOM are available, the significance and predictive value of the
      procedure is still under discussion. Moreover, cases of false-negative monitoring
      affect the surgeon's confidence in IOM. OBJECTIVE: To examine cases of false
      negative IOM to reveal structural explanations. METHODS: Between 2007 and 2010 we
      resected 115 consecutive supratentorial gliomas in or close to eloquent motor
      areas using direct cortical stimulation for monitoring of motor evoked potentials
      (MEPs). The monitoring data were reviewed and related to new postoperative motor
      deficit and postoperative imaging. Clinical outcomes were assessed during follow
      up. RESULTS: MEP monitoring was successful in 112 cases (97.4%). Postoperatively,
      30.3% of patients had a new motor deficit, which remained permanent in 12.5%.
      Progression-free follow-up was 9.7 months (range: 2 weeks to 40.6 months). In
      65.2% of all cases, MEPs were stable throughout the operation, but 8.9% showed a
      new temporary motor deficit, whereas 4.5% (5 patients) presented with permanently
      deteriorated motor function representing false-negative monitoring at first
      glance. However, these cases were caused by secondary hemorrhage, ischemia or
      resection of the supplementary motor area. CONCLUSION: Continuous MEP monitoring
      provides reliable monitoring of the motor system, influences the course of
      operation in some cases, and has to be regarded as the standard for IOM of the
      motor system. In our series, we found no false-negative MEP results.

PMID- 22469680
TI  - Effective tool or necessary evil:  intraoperative monitoring during thoracic
      aneurysm repairs.
AB  - BACKGROUND: The aim of our study was to analyze the neurophysiologic monitoring
      method with regard to its potential problems during thoracic and thoracoabdominal
      aortic open or endovascular repair. Furthermore, preventive strategies to the
      main pitfalls with this method were developed. METHODS: Between November 2000 and
      May 2007, in 97 cases, open surgery or endovascular stent graft implantation was
      performed on the thoracic or thoracoabdominal aorta. Intraoperatively,
      neurophysiologic motor and somatosensory evoked potentials were monitored.
      RESULTS: Our cases were divided into four groups: event-free patients with normal
      potentials (A, 63 cases), those with correlation of modified evoked potentials
      and neurological outcome (B, 14 cases), those with false-positive or false
      negative results (C, 4 cases), and those with medication interaction or technical
      issues (D, 16 cases). We observed a sensitivity of 93% and a specificity of 96%
      for the neurophysiologic monitoring. CONCLUSIONS: Monitoring spinal cord function
      during surgical and endovascular interventions on the thoracic and
      thoracoabdominal aorta is necessary. It can be made more effective by precisely
      analyzing the interference factors of the neurophysiologic monitoring method
      itself. Successful strategies of immediate troubleshooting could be identified.

PMID- 22469681
TI  - Intraoperative neurophysiologic monitoring:  are we really that bad?
AB  - STUDY DESIGN: Retrospective review of a prospectively collected, multicenter
      database. OBJECTIVE: To assess the rates of new neurologic deficit (NND)
      associated with spine surgery. SUMMARY OF BACKGROUND DATA: New neurologic deficit
      is a potential complication of spine surgery but previously reported rates are
      often limited by small sample size and single-surgeon experiences. METHODS: The
      Scoliosis Research Society morbidity and mortality database was queried for
      spinal surgery cases complicated by NND from 2004 to 2007, including nerve root
      deficit, cauda equina deficit, and spinal cord deficit. Use of neuromonitoring
      was assessed. Recovery was stratified as complete, partial, or none. Rates of NND
      were stratified based on diagnosis, age (pediatric, <21 years; adult, >=21
      years), and surgical parameters. RESULTS: Of the 108,419 cases reported, NND was
      documented for 1,064 (1.0%), including 662 nerve root deficits, 74 cauda equina
      deficits, and 293 spinal cord deficits (deficit not specified for 35 cases).
      Rates of NND were calculated on the basis of diagnosis. Revision cases had a 41%
      higher rate of NND (1.25%) compared with primary cases (0.89%; P < 0.001).
      Pediatric cases had a 59% higher rate of NND (1.32%) compared with adult cases
      (0.83%; P < 0.001). The rate of NND for cases with implants was more than twice
      that for cases without implants (1.15% vs. 0.52%; P < 0.001). Neuromonitoring was
      used for 65% of cases, and for cases with new nerve root deficit, cauda equina
      deficit, and spinal cord deficit, changes in neuromonitoring were reported in
      11%, 8%, and 40%, respectively. The respective percentages of no recovery,
      partial, and complete recovery for nerve root deficit were 4.7%, 46.8%, and
      47.1%, respectively; for cauda equina deficit, they were 9.6%, 45.2%, and 45.2%,
      respectively; and for spinal cord deficit, the percentages were 10.6%, 43%, and
      45.7%, respectively. CONCLUSION: Our data demonstrate that even among skilled
      spinal deformity surgeons, NNDs are inherent potential complications of spine
      surgery. These data provide general benchmark rates for NND with spine surgery as
      a basis for patient counseling and for ongoing efforts to improve safety of care.

PMID- 22469682
TI  - Low-frequency photoparoxysmal response in adults:  an early clue to diagnosis.
AB  - Intermittent photic stimulation is performed during an EEG to evoke
      photoparoxysmal response. When they appear triggered by low-frequency stimulation
      in children, they are suggestive of rare diagnosis, that is, neuronal ceroid
      lipofuscinosis. Among adults, their significance is less well understood. Low
      frequency (<5 Hz) intermittent photic stimulation was performed over a period of
      5 years during adult standard EEG. This retrospective study included all patients
      exhibiting low-frequency photoparoxysmal response. Five cases were identified.
      Three of them presented with active epilepsy (two progressive myoclonus epilepsy,
      one unclassifiable), two had visual deficiency, and three had dementia. The
      etiologies were MELAS (two), Creutzfeldt-Jakob disease (one), Kufs disease (one),
      and remained undetermined for one patient. In all patients, low-frequency
      photoparoxysmal response was observed years or months before the final diagnoses
      have been reached. Low-frequency photoparoxysmal response, classically associated
      with childhood progressive myoclonus epilepsy, seems to have a wider etiological
      spectrum in adult population. Moreover, this neurophysiological feature could be
      present before the final diagnosis in most cases. Systematically testing low
      frequencies during intermittent photic stimulation even during adult EEG seems
      warranted, particularly in a context of severe progressive neurologic
      deterioration.

PMID- 22469683
TI  - Peak detection of somatosensory evoked potentials using an integrated principal
      component analysis-walsh method.
AB  - Clinical application of somatosensory evoked potentials (SSEP) in intraoperative
      neurophysiological monitoring still requires anywhere between 200 to 500 trials,
      which is excessive and introduces a delay during surgery. In this study, the
      analysis was performed on the data recorded in 20 patients undergoing surgery
      during which the posterior tibial nerve was stimulated and SSEP response was
      recorded from scalp. The first 10 trials were analyzed using an eigen
      decomposition technique, and a signal extraction algorithm eliminated the common
      components of the signals not contributing to the SSEP. A unique Walsh transform
      operation was then used to identify the position of the SSEP event within the
      clinical requirements of 10% time in latency deviation and 50% peak-to-peak
      amplitude deviation using only 10 trials. The algorithm also shows consistency in
      the results in monitoring SSEP in up to 6-hour surgical procedures even under
      this significantly reduced number of trials.

PMID- 22469684
TI  - Pattern and motion-related visual-evoked potentials in neuroborreliosis:  follow
      up study.
AB  - Visual-evoked potentials (VEPs) were used for objective testing of visual
      functions during treatment courses of Lyme neuroborreliosis (LNB) in adult
      patients in the Czech Republic. In 30 LNB patients with originally delayed VEP
      latencies, pattern-reversal (R-VEP) and motion onset (M-VEP) VEPs were repeatedly
      examined within 1 to 8 years. Six patients had Lyme optic neuritis (ON), five of
      them displayed prolonged latencies in both R-VEPs and M-VEPs, and one had only
      abnormal R-VEPs. The VEP recovery to normal latency values was in three of them.
      In the group of 24 LNB patients without ON, 14 patients displayed prolonged
      latencies only to motion stimuli, and 10 patients had abnormal latencies in both
      R-VEPs and M-VEPs. During the follow-up period, 7 patients displayed shortening
      to normal latencies. In 5 patients, VEPs latencies improved only partially, and
      in the remaining 12 patients, VEPs did not improve at all. This study provides
      objective evidence that in LNB, most of the patients without clinically
      manifesting ON display optic pathway involvement-predominantly magnocellular
      system/dorsal stream function changes. In patients with ON, however, mainly the
      parvocellular system is affected. About half of the patients without ON improved
      with a relatively long-time course of latency shortening.

PMID- 22469685
TI  - Abnormal centroparietal ERP response in predominantly medication-naive adolescent
      boys with ADHD during both response inhibition and execution.
AB  - Abnormal event-related potential (ERP) responses have been reported in children
      and adolescents with attention deficit hyperactivity disorder (ADHD) and a
      medication history compared with in healthy controls during tasks of response
      control and conflict inhibition. This study reports neurophysiologic correlates
      of a task dependent on these cognitive functions in a large, predominantly
      medication naive, group of adolescents with ADHD compared with that in healthy
      age- and intelligence quotient (IQ)-matched controls using area-under-the-curve
      (AUC) analysis. Fifty-four adolescents with ADHD and 55 healthy comparisons
      completed a hybrid conflict and response inhibition Go/NoGo ERP task. The
      performance data showed that children with ADHD compared with controls had
      deficits in both the inhibitory measures (higher commission errors) and the Go
      process of the task (slower reaction times and enhanced omission errors). The ERP
      data showed significant impairments in brain function in the ADHD relative to the
      control group for late, endogenous ERPs (N2, P3a, and P3b), whereas no group
      differences were found for the earlier P200. All findings remained when a
      minority of children with medication history was excluded. Furthermore, deficits
      were not specific to the inhibitory processes of the task but were equally
      observed during the execution functions. Group differences were particularly
      pronounced over central and centroparietal sites across all time points,
      presumably reflecting the midline attention system mediated by anterior and
      posterior cingulate that is important for generic, condition-independent visual
      spatial attention and response selection processes. The findings demonstrate that
      adolescents with ADHD have abnormal ERP responses not only during inhibitory, but
      also execution-related processes and, furthermore, that these deficits are
      independent from medication history.

PMID- 22469686
TI  - Ulnar neuropathy in hansen disease:  clinical, high-resolution ultrasound and
      electrophysiologic correlations.
AB  - OBJECTIVE: To assess the relationship between the cross-sectional area (CSA) of
      the ulnar nerve by ultrasound (US) with clinical and electrophysiologic findings
      in Hansen ulnar neuropathy. METHODS: Twenty-one patients (42 arms) with Hansen
      disease (mean age 30.0 +/- 12.97, range 13-61 years, borderline tuberculoid 29%,
      borderline lepromatous, 19% lepromatous leprosy 42%, and pure neuritic type 10%)
      were examined clinically for ulnar sensory and motor weakness. The ulnar nerve
      was ultrasonographically examined from the wrist to the axilla, and CSA was
      measured at the level of maximum enlargement. Ulnar sensory nerve conduction was
      recorded orthodromically with ring electrodes placed at the fifth digit and
      amplitude of sensory nerve action potential (SNAP) recorded 3 cm proximal to the
      distal wrist crease. Motor conduction velocity (MCV) was recorded at the wrist
      below the elbow, below the elbow-above the elbow, and above the elbow-axilla
      segments. RESULTS: Out of the 42 arms with Hansen disease, 76% had clinically
      motor weakness, and 43% had sensory loss in the upper limbs innervated by the
      ulnar nerve. As compared with healthy subjects, the patients with Hansen ulnar
      neuropathy had a statistically significant reduction in SNAP (P <= 0.0001) and
      MCV (P <= 0.0001). It was observed that the maximum enlargement of the ulnar
      nerve in all the patients was a few centimeters above the elbow segment. The mean
      CSA of ulnar nerve above the medial epicondyle was 18 +/- 15 mm as compared with
      controls 4.83 +/- 1.12 mm (P < 0.0001). In addition to nerve thickening, US
      depicted abnormality in morphology. In 55%, the nerve was hypoechoic, and in
      7.1%, the nerve pattern was oligofascicular. Color Doppler (CD) flow signals were
      observed in all the nerves with loss of fascicular pattern and in 40% of the
      nerves that were hypoechoic. A statistically significant correlation was found
      between CSA of ulnar nerve above the medial epicondyle vs. MCV at BE-AE and
      compound muscle action potentials (CMAP) above the elbow in the patients with
      clinical motor weakness (r = -0.55, P < 0.001) and (r = -0.57, P < 0.001),
      respectively. There was no statistical significant correlation between CSA and
      SNAP in the patients with (r = -0.52, P = 0.23) and without (r = -0.07, P = 0.83)
      sensory loss. CONCLUSIONS: In leprosy patients, a positive correlation exits
      between the presence of motor weaknesses of the ulnar nerve innervated muscles,
      sonographically thickening of the ulnar nerve, and motor conduction slowing of
      the ulnar nerve at the BE-AE segment. In addition, US provided information on
      nerve morphologic alterations regarding the echo texture and location of nerve
      enlargement.

PMID- 22469687
TI  - Sleep-related breathing disorders in cerebrovascular stroke and transient
      ischemic attacks:  a comparative study.
AB  - Sleep-related breathing disorders are said to be common in patients with
      established cerebrovascular accidents. The aim of this study was to assess the
      frequency and characteristics of sleep-related breathing disorders in ischemic
      stroke and transient ischemic attacks. All patients were subjected to neurologic
      assessment, Berlin questionnaire (Arabic version), brain computed tomographic
      scan, and polysomnography along 6 to 8 hours overnight with special emphasis to
      apnea/hypopnea indices. All assessments were done for 30 patients who had stroke
      and transient ischemic attacks as well as 20 age- and sex-matched controls.
      Overall, 13.3% of patients had mild sleep apnea (apnea/hypopnea index, >5), 13.3%
      had moderate sleep apnea (apnea/hypopnea index, >15), and 34% had severe sleep
      apnea (apnea/hypopnea index, >30). The sensitivity and specificity of Berlin
      questionnaire for obstructive sleep apnea diagnosis were 55% and 100%,
      respectively, for mild sleep apnea, 56.3% and 85.7% for moderate sleep apnea,
      66.7% and 83.3% for severe condition. Berlin questionnaire is a moderate
      sensitive but highly specific screening test for sleep apnea in cerebrovascular
      diseases. Those who scored high risk should consider polysomnography to specify
      the type and severity of apnea.

PMID- 22469688
TI  - Therapeutic hypothermia and EEG.

PMID- 22469690
TI  - EEG in anoxic coma.

PMID- 22469693
TI  - Parallel optical trap assisted nanopatterning on rough surfaces.
AB  - There exist many optical lithography techniques for generating nanostructures on
      hard, flat surfaces over large areas. However, few techniques are able to create
      such patterns on soft materials or surfaces with pre-existing structure. To
      address this need, we demonstrate the use of parallel optical trap assisted
      nanopatterning (OTAN) to provide an efficient and robust direct-write method of
      producing nanoscale features without the need for focal plane adjustment.
      Parallel patterning on model surfaces of polyimide with vertical steps greater
      than 1.5 um shows a feature size uncertainty better than 4% across the step and
      lateral positional accuracy of 25 nm. A Brownian motion model is used to describe
      the positional accuracy enabling one to predict how variation in system
      parameters will affect the nanopatterning results. These combined results suggest
      that OTAN is a viable technique for massively parallel direct-write
      nanolithography on non-traditional surfaces.

PMID- 22469694
TI  - Influence of precursor solvent properties on matrix crystallinity and drug
      release rates from nanoparticle aerosol lipid matrices.
AB  - The crystallinity of drug-loaded lipid nanoparticles is believed to affect drug
      release rates; however, effective control over lipid crystallinity has not been
      achieved by current lipid nanoparticle preparation methods. The present study
      investigates control over the crystallinity of drug-loaded nanoparticle aerosol
      lipid matrices (NALM) through differences in evaporation rates of precursor
      solution drops and the subsequent control over drug release rates from these
      matrices. Gefitinib-loaded NALM were synthesized in an aerosol reactor using
      precursor solutions of gefitinib and stearic acid at a ratio of 1:4 w/w in
      organic solvents with high (dichloromethane) and low (ethyl acetate and
      chloroform) vapor pressures. Mean mobility diameter measured using a scanning
      mobility particle sizer was in the range of 123-132 nm with a unimodal
      distribution and a geometric standard deviation of 1.6-1.9. A layered particle
      structure was observed using transmission electron microscopy, which suggests
      partial drug enrichment in the surface layer. Higher drug loading (20% w/w) and
      uniform entrapment efficiencies (~100%) were achieved. The initial drug to lipid
      ratio (1:4 w/w) of the precursor solution was preserved in the synthesized lipid
      matrices. The crystallinity of the gefitinib-loaded lipid matrix was measured
      using X-ray diffraction and differential scanning calorimetry. In vitro drug
      release from gefitinib-loaded NALM in phosphate buffered saline (pH 7.2) over 10
      days showed an initial fast release period followed by a prolonged sustained
      release period with varying release rates. Gefitinib-loaded NALM synthesized at
      higher evaporation rates exhibited lower degrees of crystallinity and faster drug
      releases. These results suggest the determinant role of lipid crystallinity
      manipulated by differing evaporation rates during aerosol synthesis on drug
      releases from nanometer-sized lipid matrices.

PMID- 22469695
TI  - An atypical patient with Cowden syndrome and PTEN gene mutation presenting with
      cortical malformation and focal epilepsy.
AB  - We report the case of a girl with Cowden syndrome (CS) presenting with unilateral
      perisylvian dysplasia and with drug resistant focal seizures carrying a novel
      missense mutation 385G>A (G129R) in the PTEN gene. CS has been rarely reported in
      association with a cortical malformation or epilepsy. These cases suggest that
      cortical dysplasia needs to be suspected when a CS patient presents with drug
      resistant seizures.

PMID- 22469696
TI  - Ferroportin-1 is a 'nuclear'-negative acute-phase protein in rat liver: a
      comparison with other iron-transport proteins.
AB  - Liver is the central organ of iron metabolism. During acute-phase-response (APR),
      serum iron concentration rapidly decreases. The current study aimed to compare
      expression and localization of iron transport protein ferroportin-1 (Fpn-1) and
      of other iron import proteins after experimental tissue damage induced by
      injecting turpentine oil in the hind limbs of rats and mice. Serum and spleen
      iron concentration decreased with an increase in total liver, cytoplasmic and
      nuclear iron concentration. In liver, mRNA amount of Fpn-1, Fpn-1a, Fpn-1b, HFE,
      hemojuvelin (HJV) and hephaestin (heph) genes showed a rapid decrease. Hepcidin,
      divalent metal transporter-1 (DMT-1), transferrin (Tf) and Tf-receptor-1 (TfR1),
      TfR-2 (TfR2) gene expression was increased. Western blot analysis of liver tissue
      lysate confirmed the changes observed at mRNA level. In spleen, a rapid decrease
      in gene expression of Fpn-1, Fpn-1a, Fpn-1b, DMT-1, Tf, TfR1 and TfR2, and an
      increase in hepcidin was observed. Immunohistochemistry of DMT-1 and TfR2 were
      mainly detected in the nucleus of rat liver and spleen, whereas TfR1 was clearly
      localized in the plasma membrane. Fpn-1 was mostly found in the nuclei of liver
      cells, whereas in spleen, the protein was mainly detected in the cell membrane.
      Western blot analysis of liver fractions confirmed immunohistochemical results.
      In livers of wild-type mice, gene expression of Fpn-1, Fpn-1a and Fpn-1b was
      downregulated, whereas hepcidin gene expression was increased. In contrast, these
      changes were less pronounced in IL-6ko-mice. Cytokine (IL-6, IL-1b and TNF-a)
      treatment of rat hepatocytes showed a downregulation of Fpn-1, Fpn-1a and Fpn-1b,
      and upregulation of hepcidin gene expression. Moreover, western blot analysis of
      cell lysate of IL-6-treated hepatocytes detected, as expected, an increase of a2
      macroglobulin (positive acute-phase protein), whereas albumin (negative acute
      phase protein) and Fpn-1 were downregulated. Our results demonstrate that liver
      behaves as a 'sponge' for iron under acute-phase conditions, and Fpn-1 behaves as
      a negative acute-phase protein in rat hepatocytes mainly, but not exclusively,
      because of the effect of IL-6. These changes could explain iron retention in the
      cytoplasm and in the nucleus of hepatocytes during APR.

PMID- 22469697
TI  - Transgelin is a marker of repopulating mesangial cells after injury and promotes
      their proliferation and migration.
AB  - Mesangial cell (MC) migration is essential during glomerular repair and kidney
      development. The aim of the study was to identify marker/player for glomerular
      progenitor/reserve cells migrating into the glomerulus after MC injury and during
      glomerulogenesis in the rat. Experimental mesangial proliferative nephritis was
      induced in Sprague Dawley rats by intravenous injection of OX-7 antibody. We
      investigated mRNA expression profiles in isolated glomeruli from on days 0, 1, 2,
      3, and 5 after induction of anti-Thy1 nephritis using Affymetrix microarray
      technology. Using self-organizing maps, transgelin was identified as a new marker
      for repopulating glomerular cells. Expression of transgelin during anti-Thy1
      nephritis was investigated by northern blot, real-time PCR, western blot, and
      immunohistochemistry. Migration and proliferation assays using isolated MCs after
      transgelin knockdown by siRNA were performed to investigate the potential role of
      transgelin during glomerular repopulation. Transgelin mRNA was not detected in
      healthy glomeruli. It was strongly upregulated during the repopulation process
      starting on day 1, continued to be increased until day 5 and disappeared on day
      7. Transgelin was specifically expressed at the edge of the migratory front
      during glomerular repopulation as indicated by transgelin/OX-7 double staining.
      Transgelin expression was similar in migrating vs non-migrating MCs in vitro.
      Blocking of transgelin expression by siRNA treatment resulted in inhibition of MC
      migration and proliferation. Transgelin was also expressed in MCs during
      glomerulogenesis and in biopsies from patients with IgA nephritis. In conclusion,
      transgelin in the kidney is upregulated in repopulating MCs in vivo and supports
      their migratory and proliferative repair response after injury.

PMID- 22469698
TI  - Human monocyte-derived cells with individual hepatocyte characteristics: a novel
      tool for personalized in vitro studies.
AB  - Gender, ethnicity and individual differences in hepatic metabolism have major
      impact on individual drug response, adverse events and attrition rate during drug
      development. Therefore, there is an urgent need for reliable test systems based
      on human cells. Yet, the use of primary human hepatocytes (PHHs) is restricted by
      limited availability, invasive preparation and short-term stability in culture.
      All other cellular approaches proposed so far have major disadvantages. We
      investigated whether peripheral human monocytes after cultivation according to
      our novel protocol (monocyte-derived hepatocyte-like cells (MH cells)) can serve
      as an in vitro model for hepatocyte metabolism. Enzyme activities, synthesis
      parameters (coagulation factor VII and urea) and cytochrome (CY) P450 activities
      and induction were investigated. Furthermore, MH cells were compared with PHH
      from the same donor. Using our protocol, we could generate cells that exhibit
      hepatocyte-like properties: These cells show 71+/-9% of specific ALT activity,
      41+/-3% of CYP3A4 activity and 65+/-13% of factor VII secretion when compared
      with PHHs. Consequently, CYP-mediated acetaminophen toxicity and drug
      interactions could be shown. Moreover, the investigated parameters were stable in
      culture over at least 4 weeks. Furthermore, MH cells retain gender-specific and
      donor-specific CYP activities and toxicity profiles, respectively. MH cells show
      quantitative and qualitative approximation to human hepatocytes concerning CYP
      metabolism and toxicity. Our data support individual prediction of toxicity and
      CYP metabolism. MH cells are a novel tool to investigate long-term hepatic
      toxicity, metabolism and drug interactions.

PMID- 22469699
TI  - Extracellular matrix alterations and acute inflammation; developing in parallel
      during early induction of pulmonary fibrosis.
AB  - Pulmonary fibrosis is a hallmark of several systemic diseases such as systemic
      sclerosis. Initiation and early development is not well characterized, as
      initiation usually is unnoticed in patients, yet fibrosis has been considered a
      late event, occurring after an inflammatory phase. By utilizing an animal model,
      the starting point can be defined and the initiation process and early
      development thoroughly investigated. To investigate these processes from a
      systemic perspective, we choose a systemic administration route, instead of the
      more commonly used local administration. The aim of this work was to study the
      initiation of pulmonary fibrosis in an animal model and to investigate early
      alterations in connective tissue, cell turnover and acute immune response in lung
      parenchyma. Animals were injected subcutaneously with bleomycin, three times a
      week (w) for 1-4w (controls received saline). Total collagen was histologically
      assessed by Picro Sirius Red and Masson's Trichrome, collagen production by
      antibodies directed against N-terminal of procollagens I and III, proliferation
      by labeling with proliferating cell nuclear antigen, apoptosis by TUNEL and
      innate immunity by detecting neutrophils and macrophages. Total collagen was
      significantly increased at 1, 2 and 4w compared with controls. Procollagen I, was
      increased at 1w and remained increased, whereas procollagen III-staining was
      increased at 2w, compared with controls. Myofibroblasts were increased at all
      times as were proliferation, whereas apoptosis was increased from 2w. Neutrophils
      peaked at 1w (2779+/-820 cells/mm2) and gradually decreased, whereas macrophages
      peaked at 2w (135+/-29 cells/mm2). Subcutaneously administered bleomycin induces
      rapid alterations in connective tissue and cell turnover, suggesting a plasticity
      of the connective tissue. A transient neutrophilia is detected and increased
      number of macrophages likely represents a clearance process of said neutrophils.
      The study suggests fibrosis initiation and acute inflammation to occur in
      parallel in this model.

PMID- 22469700
TI  - Synthesis, characterization and antibacterial studies of a copper(II)
      levofloxacin ternary complex.
AB  - Solution behavior of levofloxacin (lvx) complexes with copper(II) in the presence
      and absence of phen was studied in aqueous solution, by potentiometry. The
      results obtained show that under physiological conditions (micromolar
      concentration range and pH 7.4) only copper(II):lvx:phen ternary complexes are
      stable. Hence, a novel copper(II) ternary complex of fluoroquinolone levofloxacin
      with nitrogen donor heterocyclic ligand phen was synthesized and characterized by
      means of UV-Visible and IR spectroscopy, elemental analysis and X-Ray
      crystallography. In the synthesized complex (1),
      [Cu(lvx)(phen)(H(2)O)](NO(3)).2H(2)O, levofloxacin acts as a bidentate ligand
      coordinating to the metal, in its anionic form, through the carbonyl and carboxyl
      oxygens and phen coordinates through two N-atoms forming the equatorial plane of
      a distorted square-pyramidal geometry. The fifth ligand of the penta-coordinated
      Cu(II) centre is occupied axially by an oxygen atom from a water molecule.
      Minimum inhibitory concentration (MIC) determinations of the complex and
      comparison with free levofloxacin in various E. coli strains indicated that the
      Cu-complex is as efficient an antimicrobial as the free antibiotic (both in the
      case of the dissolved synthesized complex and the complex formed following
      stoichiometric mixture of the individual components in solution). Moreover,
      results strongly suggest that the cell intake route of both species is different
      supporting, therefore, the complex's suitability as a candidate for further
      biological testing in fluoroquinolone-resistant microorganisms.

PMID- 22469701
TI  - The effects of diketopiperazines from Callyspongia sp. on release of cytokines
      and chemokines in cultured J774A.1 macrophages.
AB  - Diketopiperazines (DKPs) are a class of secondary metabolites that result from
      peptide bonds between two amino acids to form a lactam. Due to their rigid
      structure, chiral nature, and varied side chains, DKPs have been of research
      interest for their diverse bioactivities. However, little is known about whether
      DPKs stimulate the release of cytokine and chemokines in macrophage cells. The
      present aim was to study the effect of DKPs firstly isolated from sponge
      Callyspongia sp. on the release of several cytokines in murine macrophage-like
      cell line J774A.1 after stimulation in vitro, and their potential structure
      activity relationship of five natural DKPs on four representative cytokines,
      interferon-gamma (IFN-gamma), pro-inflammatory (tumor necrosis factor, TNF
      alpha), anti-inflammatory cytokine (interleukin-10, IL-10), and chemokine
      (monocyte chemoattractant protein-1, MCP-1). Results suggested that these five
      DKPs, especially DKP 1 bearing 3-hydroxyl-l-proline (l-Hyp), might be useful as a
      promising macrophage cytokines stimulator.

PMID- 22469702
TI  - Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity
      against Mycobacterium tuberculosis.
AB  - A high-throughput screen against PknB, an essential serine-threonine protein
      kinase present in Mycobacterium tuberculosis (M. tuberculosis), allowed the
      identification of an aminoquinazoline inhibitor which was used as a starting
      point for SAR investigations. Although a significant improvement in enzyme
      affinity was achieved, the aminoquinazolines showed little or no cellular
      activity against M. tuberculosis. However, switching to an aminopyrimidine core
      scaffold and the introduction of a basic amine side chain afforded compounds with
      nanomolar enzyme binding affinity and micromolar minimum inhibitory
      concentrations against M. tuberculosis. Replacement of the pyrazole head group
      with pyridine then allowed equipotent compounds with improved selectivity against
      a human kinase panel to be obtained.

PMID- 22469703
TI  - Isoquinoline derivatives as potent CRTH2 receptor antagonists: synthesis and SAR.
AB  - Synthesis and structure-activity relationship of a novel series of isoquinoline
      CRTH2 receptor antagonists are described. One of the most potent compounds,
      TASP0376377 (6m), showed not only potent binding affinity (IC(50)=19 nM) but also
      excellent functional antagonist activity (IC(50)=13 nM). TASP0376377 was tested
      for its ability of a chemotaxis assay to show the effectiveness (IC(50)=23 nM),
      which was in good agreement with the CRTH2 antagonist potency. Furthermore,
      TASP0376377 showed sufficient selectivity for binding to CRTH2 over the DP1
      prostanoid receptor (IC(50)>1 MUM) and COX-1 and COX-2 enzymes (IC(50)>10 MUM).

PMID- 22469705
TI  - Quantum mechanically guided design of Co43Fe20Ta(5.5)X(31.5) (X=B, Si, P, S)
      metallic glasses.
AB  - A systematic ab initio molecular dynamics study was carried out to identify
      valence electron concentration and size induced changes on structure, elastic and
      magnetic properties for Co(43)Fe(20)Ta(5.5)X(31.5) (X=B, Si, P, S). Short range
      order, charge transfer and the bonding nature are analyzed by means of density of
      states, Bader decomposition and pair distribution function analysis. A clear
      trend of a decrease in density and bulk modulus as well as a weaker cohesion was
      observed as the valence electron concentration is increased by replacing B with
      Si and further with P and S. These changes may be understood based on increased
      interatomic distances, variations in coordination numbers and the electronic
      structure changes; as the valence electron concentration of X is increased the X
      bonding becomes more ionic, which disrupts the overall metallic interactions,
      leading to lower cohesion and stiffness. The highest magnetic moments for the
      transition metals are identified for X=S, despite the fact that the presence of X
      generally reduces the magnetic moment of Co. Furthermore, this study reveals an
      extended diagonal relationship between B and P within these amorphous alloys.
      Based on quantum mechanical data we identify composition induced changes in short
      range order, charge transfer and bonding nature and link them to density,
      elasticity and magnetism. The interplay between transition metal d band filling
      and s-d hybridization was identified to be a key materials design criterion.

PMID- 22469706
TI  - Laparoscopic HIPEC in the treatment of advanced ovarian cancer.
AB  - BACKGROUND/AIMS: HIPEC has been recently recommended as the 'new standard of
      care' for advanced ovarian cancer patients to treat residual disease, a
      recommendation based on the good results reported by many single institution
      studies. This study aims to elucidate whether cyto-reductive surgery for advanced
      stage IV ovarian cancer combined with laparoscopic HIPEC has any value in the
      management of advanced ovarian cancer. METHODOLOGY: From January 2007 to October
      2011, 31 patients with stage IV ovarian cancer were enrolled. The inclusion
      criteria were stage IV epithelial ovarian cancer, with no evidence of extra
      abdominal metastasis, and without previous systemic chemotherapy. Patients were
      randomly divided into two groups, group A and group B, which consisted of 12
      patients who received laparoscopic HIPEC in a neo-adjuvant setting, and 19
      patients who received laparoscopic HIPEC in an adjuvant setting, respectively.
      RESULTS: Overall response rate after Laparoscopic HIPEC (neo-adjuvant and
      adjuvant) was 100%. Macroscopic images recorded during initial laparoscopy and
      subsequent laparoscopies revealed a dramatic decrease in the size of the
      neoplastic deposits accompanied with a decrease in their absolute number.
      DISCUSSION: The results of this study indicate that laparoscopic HIPEC preceding
      multi-organ radical surgery has been seen to be associated with optimal short and
      long-term results, and promising OS and DFS. They also demonstrate the
      therapeutical advantage of neo-adjuvant initial approach over adjuvant approach.

PMID- 22469707
TI  - Oxidative DNA damage and repair in chronic atrophic gastritis and gastric cancer.
AB  - BACKGROUND/AIMS: Increased production of reactive oxygen species, which cause
      oxidative DNA damage, is considered to be related to gastric carcinogenesis. The
      aim of this research was to detect the 8-OHdG and the expression of hOGG1and
      MnSOD, in human gastric mucosa with chronic atrophic gastritis (CAG) and gastric
      carcinoma (GC) comparing with normal controls (NC). METHODOLOGY: The level of 8
      OHdG in gastric biopsy specimens was assessed with immunohistochemistry. The
      expression level of hOGG1and MnSOD in gastric tissues was assessed with Western
      blot. RESULTS: The 8-OHdG staining in CAG and GC mucosa was stronger than control
      (p<0.01). hOGG1 was expressed to a lower degree in GC and CAG when compared to
      the control group (both p<0.01) and the level of GC was even lower than CAG
      (p<0.05). MnSOD was expressed to a greater degree in GC group when compared to
      the control (p<0.05). CONCLUSIONS: CAG patients who express 8-OHdG highly should
      be monitored for the potentially occurrence of GC. The lower lever of hOGG1 in
      CAG and GC with higher level of 8-OHdG implies that hOGG1 is closely related to
      oxidative DNA damage and may lead to carcinoma. The increasing expression of
      MnSOD in the gastric mucosa may indicate the occurrence of gastric cancer.

PMID- 22469708
TI  - Timing of capsule endoscopy influences the diagnosis and outcome in obscure-overt
      gastrointestinal bleeding.
AB  - BACKGROUND/AIMS: Capsule endoscopy (CE) has high positive (95%) and negative
      predictive values (83- 100%) for the bleeding source in patients with obscure
      gastrointestinal bleeding (OGIB) but the diagnostic yield is influenced by the
      timing of the examination and the nature of the bleeding. METHODOLOGY: We
      investigated the role of early CE in the diagnosis of patients with overt OGIB.
      Patients were divided into 4 groups according to the interval between bleeding
      and CE. The diagnosis rate and clinical outcomes including type of intervention
      and recurrent bleeding were compared. The association between the timing of CE
      and small bowel lesions detected by CE was also analysed. RESULTS: Ninety
      patients with overt OGIB underwent CE. CE revealed the bleeding source in 46
      patients (51%). The diagnosis rate was 73%, 48%, 50% and 35% in 1st, 2nd, 3rd and
      4th quartiles (p=0.08). The duration between bleeding and CE was shorter for
      patients with angioectasia than for those with other abnormalities. The
      proportion of surgeries and endoscopic interventions was significantly higher in
      1st and 2nd quartiles than 3rd and 4th quartiles (p=0.048). CONCLUSIONS: Earlier
      timing of CE achieved a higher diagnostic yield for patients with overt OGIB and
      consequently resulted in a higher intervention rate.

PMID- 22469709
TI  - Pancreatic resection for metastases from renal cancer: long term outcome after
      surgery and immunotherapy approach - single center experience.
AB  - BACKGROUND/AIMS: Natural history of renal cell carcinoma includes metastases to
      the pancreas. The literature reports that selected patients may have benefits by
      pancreatic resection in terms of long term survival. We report patient outcome
      and considerations on immunotherapy approach. METHODOLOGY: From 2001 to 2010
      eight patients underwent pancreatic resection for metastases from renal cancer.
      We reviewed surgical outcome and following treatment (conventional chemotherapy:
      5FU-Vindesine; Immunotherapy: Interleukin 2 - Interferon - Dendritic cells) of
      these patients. RESULTS: All patients underwent radical pancreatic resection (7
      spleno-pancreatectomies; 1 segmental pancreatic resection) and were R0 after
      surgery. No postoperative mortality was reported. Morbidity was 37% (2 distal
      leakage; 1 pneumonitis). Two patients did not receive any further treatment; 2
      patients received conventional chemotherapy; 2 patients received immunotherapy
      (interleukin2 + interferon); 2 patients received dendritic cells (DC) interleukin
      2 infusion. Three years overall survival rate was 55%. Disease free survival
      after 3 years was 30%. CONCLUSIONS: Our data confirm that pancreatic resection
      should be offered to selected patients with no mortality and low morbidity. Long
      term survival is achievable, but recurrence rate after surgery is high.
      Immunotherapy could be effective to control tumour progression especially in
      selected cases where DC may be used.

PMID- 22469710
TI  - An analysis of a second-line S-1 monotherapy for gemcitabine-refractory biliary
      tract cancer.
AB  - BACKGROUND/AIMS: Gemcitabine is widely used as a first-line therapy for biliary
      tract cancer (BTC). However, few studies have been conducted to analyze second-
      line therapies. METHODOLOGY: From 33 patients who had been administered
      gemcitabine following resection between May 2005 and August 2007, we
      retrospectively analyzed the safety and efficacy of S-1 in 11 cases who received
      S-1 as second-line therapy due to recurrence or relapse of the primary disease.
      RESULTS: Among the adverse events (AEs) observed during S-1 administration, the
      most common was a decrease in the concentration of hemoglobin, followed by
      thrombocytopenia. No Grade 4 AEs or worse were detected. In addition, the AEs and
      their respective severity strongly resembled those of gemcitabine used as a first
      line therapy. There were 7 cases that could be evaluated according to RECIST
      criteria, of which 1 was considered in the partial response and 3 as stable
      disease. The medians of time to progression after S-1 administration and survival
      after S-1 administration were 5.6 months and 31 months, respectively.
      CONCLUSIONS: S-1 could be taken safely as a second-line therapy without provoking
      severe AEs. By preventing the cessation of S-1 administration due to its AEs,
      more continued S-1 administration could lead to a better prognosis for BTC.

PMID- 22469711
TI  - Role of hilar resection in the treatment of hilar cholangiocarcinoma.
AB  - BACKGROUND/AIMS: The aim of this study was to clarify the role of bile duct
      resection without hepatectomy (hilar resection) in hilar cholangiocarcinoma.
      METHODOLOGY: We retrospectively compared surgical results for hilar
      cholangiocarcinoma between 8 patients treated with hilar resection and 21
      patients treated with hepatectomy. RESULTS: All hilar resections were performed
      for Bismuth type I or II tumors with T2 or less lesions, whereas hepatectomy was
      done for type III or IV tumors excluding one type II tumor. R0 resection was
      equally achieved in both groups (62.5% in hilar resection group and 76.2% in
      hepatectomy group, p=0.469) and overall 5-year survival rates were comparable
      (21.9% vs. 23.6%, p=0.874). With respect to gross tumor appearance, R0 resection
      was achieved in all patients with papillary tumor in both groups with the
      excellent 5-year survivals (100% vs. 100%). In patients with nodular and flat
      tumors, R0 resection was achieved less frequently in the hilar resection vs.
      hepatectomy group (50% vs. 77.8%) mainly due to failure to clear the proximal
      ductal margin, resulting in poorer 5-year survival (0% vs. 18.7%). CONCLUSIONS:
      Hilar resection may be indicated for papillary T1 or 2 tumors in Bismuth type I
      or II cholangiocarcinoma.

PMID- 22469712
TI  - The influence of tumor cell entrapment phenomenon on the natural history of
      Pseudomyxoma peritonei syndrome.
AB  - BACKGROUND/AIMS: Pseudomyxoma peritonei syndrome (PMP) may be associated with
      slow "benign" or malignant process. However, the natural history of this disease
      is slow progression to death. Its treatment is variable and controversial. In
      this current study we have compared the patients with Pseudomyxoma peritonei
      syndrome with recurrences due to the cell entrapment hypothesis. METHODOLOGY:
      Data were derived from a database of patients with PMP treated at our hospitals
      from 2004 to 2009. All patients had undergone various surgical operations prior
      to referral to our institutions for definitive treatment. All patients had
      recurrences in special sites due to entrapment of malignant cells. RESULTS: There
      are 6 patients, four men and two women. The initial clinical presentation of the
      disease was hernia in one, appendicitis in three and ovarian mass in one. The
      mean time from the initial operation to be definitive management was 23.5 months
      with an average of 1.83 operations per patient. After cytoreduction and
      hyperthermic intraperitoneal chemotherapy (HIPEC) the mean survival was 31 months
      with minimal recurrences and only 0.3 operations per patient. CONCLUSIONS: Our
      data suggest that the patients should be referred to a center with a peritoneal
      surface malignancy program after the PMP diagnosis as soon as possible.
      Incomplete debulking procedures and minimal invasive operations promote
      uncontrollable intraabdominal tumor growth due to tumor cell entrapment and the
      tendency of PMP to grow at wound sites.

PMID- 22469713
TI  - Prevalence of anaemia at diagnosis of colorectal cancer: assessment of associated
      risk factors.
AB  - BACKGROUND/AIMS: The aim of this study was to report the prevalence of anaemia in
      patients with cancer located in different anatomical segments of the colon and
      rectum and to assess possible risk factors for this anaemia. METHODOLOGY: The
      study included 1189 patients referred during 1980-2004 with a colorectal
      adenocarcinoma. Data were obtained from hospital records and from the Norwegian
      Cancer Registry. Risk factors for anaemia were analyzed in multivariable logistic
      regression analysis. The WHO definition of anaemia was used. RESULTS: The
      prevalence of anaemia diminished gradually and linearly as the location of the
      tumours was more distal towards the rectum. Anaemia was found in 74.7% (215/288)
      of the patients with cancer in the coecum or ascending colon, 57.1% (48/84) in
      the transverse colon, 40.0% (180/300) in the sigmoid and 30.5% (114/374) in the
      rectum. In the multivariable analysis, age, location of the tumour and T-stage
      remained associated with anaemia, whereas the histological differentiation of the
      tumour, N-stage, M-stage, period of admission, duration of symptoms and rectal
      bleeding were not. CONCLUSIONS: Anaemia was common, especially in patients with
      proximal colon cancer. T-stage but not N-stage or M-stage was associated with
      anaemia.

PMID- 22469714
TI  - Mortality and anastomotic leakage after anterior resection for rectal cancer.
AB  - BACKGROUND/AIMS: The aim of the study was to analyze the mortality and
      symptomatic anastomotic leak following stapled anastomosis after anterior
      resection for rectal cancer. METHODOLOGY: We analyzed retrospectively 161
      patients subjected to elective anterior resection of the rectum. There were 102
      (63.3%) men and 59 (37.7%) women. The patients were divided into two groups
      according to tumor location: group I - 129 (80.1%) patients with tumor located >6
      cm from the anal verge and group II - 32 (19.9%) patients with tumor located =6
      cm. RESULTS: Anastomotic leak was found in 5 (3.1%) patients, three (2.3%) from
      group I and two (6.2%) from group II (p<0.26). Anastomotic leak was found more
      often in patients with renal failure (p<0.0023) and in those who had undergone
      RBC concentrate transfusion (p<0.0045). Seven (4.3%) patients died in the
      postoperative period. Deaths occurred more frequently in patients with valvular
      heart disease (p<0.00002), renal failure (p<0.0047) and in those given
      concentrates of RBC (p<0.045). CONCLUSIONS: Incidence of postoperative surgical
      complications after resection for rectal cancer is not high and is acceptable;
      however, there is an increased risk of leakage after low anterior resection.
      Renal failure as well as RBC concentrate transfusion have an influence on
      mortality and anastomotic leak.

PMID- 22469715
TI  - Is gynecological cancer a new indication for surveillance colonoscopy in Korea?
AB  - BACKGROUND/AIMS: Previous studies regarding the risk for colorectal neoplasms in
      women with a prior diagnosis of gynecological cancer have revealed conflicting
      results. Therefore, we conducted a cross-sectional study to quantify the risk for
      colorectal neoplasms in patients with gynecological cancers. METHODOLOGY: A total
      of 4613 women (including 27, 51 and 92 women with a prior diagnosis of
      endometrial, ovarian and cervical cancers, respectively) >20 years of age were
      recruited prospectively from 9 tertiary medical centers in Korea between January
      2008 and February 2009. All participants underwent complete colonoscopies for
      vague abdominal signs or symptoms or for colorectal cancer screening. Several
      risk factors for colorectal neoplasms and a prior history of gynecological cancer
      were compared between women with and without colorectal neoplasms. RESULTS: The
      risk for colorectal neoplasms was only elevated among women with previous
      endometrial cancer, but with ovarian or cervical cancer, particularly when
      diagnosed at <50 years of age (adjusted OR=3.7; 95% CI=1.0-13.3, p=0.016).
      CONCLUSIONS: This study demonstrated a higher risk for colorectal neoplasms in
      women with previous endometrial cancer, particularly when diagnosed at <50 years
      of age. Greater emphasis on colorectal cancer screening in this population may be
      necessary.

PMID- 22469716
TI  - Doppler perfusion index and colorectal hepatic metastases: personal experience
      and review of the literature.
AB  - BACKGROUND/AIMS: To evaluate the role of the hepatic perfusion in the assessment
      of the colorectal cancer. METHODOLOGY: For this research 18 patients affected by
      colorectal cancer were enrolled. All the patients were submitted to the
      evaluation of the Doppler Perfusion Index (DPI) which represents the ratio of
      hepatic arterial to total liver blood flow. RESULTS: The correlation between the
      evaluation of the Doppler Perfusion Index and the occurrence of the liver
      metastases did not show false negative but has highlighted 6 false positive,
      achieved a good sensitivity and very low specificity. CONCLUSIONS: A review of
      the literature and the results obtained in our study suggest that DPI may be
      helpful in detection of hepatic metastases.

PMID- 22469717
TI  - Cholecystitis, cholelithiasis and hyperbilirubinemia after esophagectomy.
AB  - BACKGROUND/AIMS: A high incidence of hyperbilirubinemia and an increased
      incidence of gallbladder disorders after esophagectomy have been reported.
      Moreover, several studies have documented an increased incidence of gallbladder
      disease in patients receiving long-term total parenteral nutrition. We studied
      the incidence of cholecystitis and cholestasis and hyperbilirubinemia associated
      with total parenteral nutrition after esophagectomy. METHODOLOGY: We
      retrospectively studied 42 patients who underwent esophagectomy. These patients
      were divided into 2 groups: the hyperbilirubinemia group and the non
      hyperbilirubinemia group. The incidence of cholecystitis or cholestasis after the
      surgery was compared between the 2 groups. RESULTS: The mean total serum
      bilirubin level of the hyperbilirubinemia group (2.40+/-0.35mg/dL) was
      significantly higher than that of the non-hyperbilirubinemia group (1.20+/
      0.34mg/dL; p<0.0001). No significant differences were observed between the 2
      groups with respect to the mean duration for which total parenteral nutrition was
      required around the time of the operation (i.e. pre- and postoperatively) and the
      incidence rate of cholecystitis or cholestasis after esophagectomy. CONCLUSIONS:
      Hyperbilirubinemia after esophagectomy was frequently observed; however, it may
      not contribute to gallbladder problems. We suggest that parenteral modalities
      such as tube feeding should be initiated soon after surgery to prevent
      gallbladder problems after esophagectomy.

PMID- 22469718
TI  - Successful treatment of esophageal repair with omentum for the spontaneous
      rupture of the esophagus (Boerhaave's syndrome).
AB  - Spontaneous rupture of the esophagus (Boerhaave's syndrome) is a critical
      disease. Most patients should undergo surgery for primary closure and drainage of
      the mediastinum and thorax. We treated a total of 7 cases of spontaneous rupture
      of the esophagus between December 2000 and August 2007. The time delay was 3
      hours to 4 days (mean 16.7 hours) and the length of longitudinal tears ranged
      from 3 to 10cm (mean: 5.6cm). All cases underwent pedicled omental flap repair to
      reinforce the suture line. We introduced our technique by pedicled omental flap
      for successful treatment.

PMID- 22469719
TI  - Surgical management of acute upper gastrointestinal bleeding:still a major
      challenge.
AB  - BACKGROUND/AIMS: Acute upper gastrointestinal bleeding (UGIB) that cannot be
      managed with conservative interventional techniques is a life-threatening
      condition. This study assesses patient outcome and the role of different risk
      factors. METHODOLOGY: We retrospectively analyzed data from 91 patients (58 men,
      33 women) admitted between 2000 and 2009 and who underwent surgery for UGIB
      requiring transfusion. RESULTS: Mean patient age was 67.4 years. Overall
      mortality was 34.1%. Causes of bleeding were duodenal ulcer in 57 patients
      (62.6%) and gastric ulcer in 25 (27.5%). A median number of 21 blood units (range
      6-120) were transfused. Surgical treatment consisted of non-resective surgery
      (52.7%), Billroth II (31.9%), Billroth I (4.4%) or gastric wedge resection
      (4.4%). The use of anticoagulants (p=0.040), a need for postoperative ventilation
      (p=0.007) and an intensive care unit (ICU) length of stay >7 days (p=0.004) were
      identified as significant risk factors for mortality. Transfusions of more than
      10 units of blood (p=0.013), the need for further surgery (p=0.021), a prolonged
      ICU length of stay (p=0.000) and recurrent bleeding (p=0.029) we identified as
      significant risk factors for postoperative complications (such as pneumonia,
      sepsis, re-bleeding and anastomotic leakage). CONCLUSIONS: Over the past decade,
      mortality has not decreased in patients requiring surgery for acute UGIB despite
      diagnostic and therapeutic advances, explained by the fact that these cases
      represent a negative selection of patients after unsuccessful conservative
      treatment as well as by the rising age of the population and associated increases
      in comorbidity. Resective surgery, a need for postoperative ventilation and a
      prolonged ICU length of stay should be added to the list of significant risk
      factors for mortality.

PMID- 22469720
TI  - Gastrointestinal bleeding associated with antithrombotic therapy in the elderly
      in Japan.
AB  - BACKGROUND/AIMS: We summarize data of patients with gastrointestinal bleeding
      (GIB) and discuss the relationship between antithrombotic drug use and age in
      patients with GIB. METHODOLOGY: One-hundred and twenty patients with GIB were
      divided into two groups according to age (=75 years old and <75 years old). The
      causes and clinical outcome of each group were compared. RESULTS: Forty-two
      patients received antithrombotic therapy. The main antithrombotic drugs were low
      dose aspirin (38 patients), ticlopidine (5 patients) and warfarin (3 patients).
      Compared with younger GIB patients, elderly patients had more coexisting illness
      and antithrombotic drugs. In patients taking antithrombotic drugs, upper GIB is
      more frequent than those not taking antithrombotic drugs (p<0.05) and
      antithrombotic drugs were the risk for GIB from erosive lesions of the esophagus
      or stomach. In the lower gastrointestinal tract, there was no difference of
      incidence related to antithrombotic use. The initial endoscopic hemostasis was
      performed in 14 patients. Eight varices patients received endoscopic vanding and
      6 of 43 gastroduodenal ulcer patients had mechanical clip hemostasis.
      CONCLUSIONS: From our findings, antithrombotic drugs were considered to be a risk
      for GIB. It might be important to prevent or minimize GIB in elderly patients
      prescribed antithrombotic drugs.

PMID- 22469721
TI  - Comparison of the diagnostic yield of "MiroCam" and "PillCam SB" capsule
      endoscopy.
AB  - BACKGROUND/AIMS: Although capsule endoscopy (CE) is widely used to evaluate small
      bowel diseases, its diagnostic power has not been firmly established. The aim of
      this study was to compare the abilities of the "Miro- Cam" and "PillCam SB" to
      detect Z-line and duodenal papillae. METHODOLOGY: The records of 141 patients who
      had CE studies between January 2004 and December 2008 were retrospectively
      reviewed by two gastroenterologists. All patients had undergone
      esophagogastroduodenoscopy. The primary endpoint of the present study was the
      detection rate of Z-line and duodenal papillae. RESULTS: Among the 141 patients,
      84 (60%) received CE using the PillCam SB and 57 (40%) using the MiroCam. There
      were no statistical differences in the baseline characteristics of the patients
      between the two groups. The Z-line detection rate was 36.9% with the PillCam SB
      and 47.7% with the MiroCam (p=0.227). The detection rate of duodenal papillae was
      13.1% with the PillCam SB and 29.8% with the MiroCam (p=0.018). CONCLUSIONS:
      While the devices were similar for visualizing the Z-line, the MiroCam showed a
      higher diagnostic yield for detecting duodenal papillae than did the PillCam SB.
      The sensitivities of both for visualizing duodenal papillae were still limited,
      however.

PMID- 22469722
TI  - Surgical treatment for hepatic alveolar echinococcosis: report of 50 cases.
AB  - BACKGROUND/AIMS: The purpose of this study is to present the surgical treatment
      of hepatic alveolar echinococcosis and evaluate the treatment outcomes.
      METHODOLOGY: A retrospective analysis was made on 50 patients admitted between
      2000 and 2008. All the patients were divided into two groups, 26 patients for the
      radical surgery group and 24 for the palliative surgery group. RESULTS: In the
      palliative surgery group, 10 patients died during the follow-up period, 2
      patients presented with brain metastasis and 4 patients with lung metastasis, 1
      patient had multiple lesions in the liver, 1 patient who received left
      hepatectomy had a new lesion in caudate lobe of the liver, 4 patients had
      postoperative jaundice, 3 had cholangitis and 4 patients had biliary leaks. There
      were also 3 patients lost in the follow-up period. In the radical surgery group,
      22 patients were alive and asymptomatic without recurrence during the follow-up
      period, 3 patients had recurrent cholangitis and 4 patients had biliary leaks.
      Three patients were lost during the followup period in this group. CONCLUSIONS:
      Radical resection appears to be best treatment of hepatic alveolar echinococcosis
      and palliative operation may cause a series of severe complications leading to
      death.

PMID- 22469723
TI  - Western blotting analysis for quantitative detection of CYP2C19 expression in
      liver tissues in the setting of living donor liver transplantation.
AB  - BACKGROUND: The cytochrome P450 (CYP) drug-metabolizing enzymes play an important
      role in cellular metabolism. Therapeutic failure or drug toxicity in the period
      after liver transplantation (LT) is influenced by the drug metabolizing capacity
      of the graft. The expression levels of CYP2C19 enzyme are often used as an
      indicator of the functioning of the CYP system. The aim of the present study was
      to assess the CYP2C19 protein expression in the setting of living donor liver
      transplantation (LDLT) by using western blotting analysis. METHODOLOGY: We
      performed CYP2C19 genotyping of liver biopsy samples obtained from 24 donors and
      8 recipients each in the pre- and post-LT periods, after which we analyzed the
      CYP enzyme activity by using western blotting analysis. RESULTS: The CYP2C19/beta
      actin ratio, which was an indicator of CYP expression, was 61.75% (23-100%) in
      donors, 59.13% (15-100%) in pre-LT recipients and 46.71% (12-67%) in post-LT
      recipients (p>0.05). The CYP2C19 expression levels associated with different
      genotypes were as follows: homozygous extensive metabolizers (HomEMs; n=24),
      56.63+/-24.74%; heterozygous extensive metabolizers (HetEMs; n=15), 63.0+/-25.14%
      and poor metabolizers (PMs; n=1), 82.0% (p>0.05). CONCLUSIONS: Western blotting
      analysis showed low CYP2C19 protein expression not only in samples from the pre-
      and post-LT recipients but also from the donors.

PMID- 22469724
TI  - Impact of previous hepatectomy on short-term outcomes of repeat hepatectomy for
      liver tumors with a special concern of operative time.
AB  - BACKGROUND/AIMS: Repeat hepatectomy is widely accepted as a treatment for primary
      or metastatic liver malignancy. However, it entails a longer operative time and
      is associated with additional operative risks. The goal of the present study was
      to evaluate the impact of previous hepatectomy on the short-term outcomes of
      repeat hepatectomy, especially in operative time. METHODOLOGY: A retrospective
      review of prospectively collected data from patients who underwent primary
      hepatectomy (n=166) and repeat hepatectomy (n=65) in a single institution.
      RESULTS: Operative time was significantly longer for repeat hepatectomy than for
      primary hepatectomy (284min vs. 250min, p=0.04). There were no significant
      differences between the two groups with respect to intraoperative blood loss,
      intraoperative blood transfusion, morbidity, mortality and length of hospital
      stay. Multivariate analysis demonstrated that third or subsequent hepatectomy and
      tumor location in the caudate lobe at the repeat hepatectomy significantly
      prolonged operative time. CONCLUSIONS: Repeat hepatectomy has similar short-term
      outcomes to primary liver resection. However, repeat hepatectomy is a time
      consuming operation, especially in patients with tumors in the caudate lobe or
      for those undergoing their third or subsequent hepatectomy.

PMID- 22469725
TI  - Changes in peripheral T-lymphocyte subsets in acute-on-chronic liver failure
      patients with artificial liver support system.
AB  - BACKGROUND/AIMS: HBV-related acute-on-chronic liver failure (AoCLF) is associated
      with a high mortality rate. An artificial liver support system (ALSS) is a newly
      emerging therapeutic option, which can be implemented in routine patient care. In
      order to determine if any pretreatment immunological parameter could be an
      indicator to evaluate immune states for the outcome of the AoCLF patients, we
      analyzed the relationship between the level of T-lymphocyte subsets (CD4+, CD8+,
      CD4/CD8 ratio) and its therapeutic effect and prognosis. METHODOLOGY: Sixty-three
      patients with AoCLF were enrolled in 2 groups (ALSS plus routine-care, n=29 and
      routine-care only, n=34). In the ALSS group, there were 17 survivors (17/29),
      while in the routine-care group there were 11 survivors (11/34), both after 30
      days of treatment. Twenty-three healthy donors were used as the control group.
      The number of CD4 and CD8 T cells was detected by flow cytometry and the ratio of
      CD4/ CD8 was calculated on admission and on days 7, 14, 21 and 30, during
      hospitalization. RESULTS: More dramatic increased CD4/CD8 ratio in the ALSS
      survivors (form 0.92+/-0.18 to 1.26+/-0.24, p<0.01) than the medical survivors
      (form 0.86+/-0.16 to 1.09+/-0.16, p<0.05) after 30 days of treatment. A declined
      tendency was observed in nonsurvivors. CONCLUSIONS: T-lymphocyte subsets may be
      important in the pathogenesis of the AoCLF and ALSS may represent a reliable
      hepatic support device for Ao- CLF.

PMID- 22469726
TI  - The usefulness of measuring liver stiffness by transient elastography for
      assessing hepatic fibrosis in patients with various chronic liver diseases.
AB  - BACKGROUND/AIMS: The degree of hepatic fibrosis is an important factor for
      prognosis and management of patients with chronic liver disease; however, liver
      biopsy is an invasive method of measuring fibrosis. Here, we investigated the
      diagnostic utility of liver stiffness, as measured by transient elastography in
      assessing hepatic fibrosis of viral chronic liver disease and nonalcoholic fatty
      liver disease (NAFLD). METHODOLOGY: Four hundred and nine eligible patients
      underwent transient elastography to measure liver stiffness. Liver biopsy for
      histopathological assessment of fibrosis (F0-F4) was performed in 71 of these
      patients. Serum levels of hyaluronic acid were determined in 110 patients. We
      assessed liver stiffness in several chronic liver diseases and compared
      correlations among liver stiffness, hepatic fibrosis stage and serum hyaluronic
      acid levels. RESULTS: A steady stepwise increase in liver stiffness was observed
      with progressing severity of hepatic fibrosis (p<0.0001) in 71 patients who
      underwent liver biopsy. In 32 chronic viral hepatitis patients, measuring liver
      stiffness was useful for differentiating between F1, or F2, or F3 and F4, while
      in 32 NAFLD liver stiffness can differentiate between F0 and F1, F2, or F3, F1
      and F3 or F4 and F2 and F4. There was no significant correlation between liver
      fibrotic stages and serum hyaluronic levels. CONCLUSIONS: The present data
      advocates measuring liver stiffness for assessing hepatic fibrosis is more
      sensitive in NAFLD than viral chronic diseases, and liver stiffness is useful
      compared to serum hyaluronic acid level in estimating hepatic fibrosis.

PMID- 22469727
TI  - Effectiveness of using ultrasonically activated scalpel in combination with
      radiofrequency dissecting sealer or irrigation bipolar for hepatic resection.
AB  - BACKGROUND/AIMS: Many kinds of transection devices have been developed but there
      are very few reports on the effectiveness of using ultrasonically activated
      scalpel with a hook blade in combination with a thermo-coagulating device for
      hepatectomy. METHODOLOGY: We studied 533 consecutive patients who underwent
      hepatectomy for primary disease and for living- related liver transplantation
      (LRLT) donors preformed using ultrasonically activated scalpel with a hook blade
      along with a saline-linked radiofrequency dissecting sealer (TL group, n=215) or
      bipolar cautery with a saline-irrigation system (IB group, n=318). Intraoperative
      blood loss, operative time, postoperative laboratory data collected over a week
      and the incidence of postoperative complications were analyzed in accordance with
      the pre-existing liver conditions. RESULTS: The median operative time required to
      perform partial hepatectomy and hemihepatectomy in liver tumor cases was found to
      be significantly shorter in the TL group than in the IB group. There was no
      significant difference in the amount of blood loss between the 2 groups.
      Postoperative laboratory data was favorable and the overall complication rate
      after hepatectomy was 9.01%. CONCLUSIONS: Ultrasonically activated scalpel with a
      hook blade used in combination with a thermo-coagulation device yielded favorable
      intra and postoperative outcomes.

PMID- 22469728
TI  - Hybrid ablation using percutaneous and endoscopic approach for multi-nodular
      hepatocellular carcinomas.
AB  - BACKGROUND/AIMS: To investigate the efficacy and the safety of a hybrid ablation
      combining a percutaneous and endoscopic approach for multi-nodular hepatocellular
      carcinomas. METHODOLOGY: Hybrid ablation consists of a percutaneous approach for
      deep-sited tumors and an endoscopic approach for superficial ones. Between
      January 1991 and December 2007, forty eight patients with 139 nodules were
      treated with hybrid ablation. The perioperative clinical data and prognosis of
      the hybrid approach group were compared with 15 patients with superficial and
      deep-sited multinodular HCCs treated by the pure endoscopic ablation. RESULTS:
      With regard to the deep-site of the liver tumors, the complete disappearance of
      tumor enhancement was observed in 76 of 77 tumors (98.7%) in the hybrid ablation
      group and 15 of 18 tumors (83.3%) in the pure endoscopic ablation group (p=0.02).
      The mean operation time (236.5min), the mean amount of intraoperative bleeding
      (20.3g), the median days of postoperative hospital stay (14 days), major
      complication rates (10.4%) and the 5-year overall survival (42%) in the hybrid
      ablation group were similar to the pure endoscopic group. CONCLUSIONS: Hybrid
      ablation is a clinically useful treatment for multi-nodular hepatocellular
      carcinomas located in both the superficial and deep-site of the liver.

PMID- 22469729
TI  - The significance of serum AFP cut-off values, 20 and 400 ng/mL in curatively
      resected patients with hepatocellular carcinoma and cirrhosis might be of
      difference.
AB  - BACKGROUND/AIMS: The significance of preoperative serum a-fetoprotein (AFP) level
      in hepatocellular carcinoma (HCC) treated with different modalities remains
      controversial. Besides, many cut-off values have been used. The present study
      aims to clarify significance of two major ones in HCC with cirrhosis.
      METHODOLOGY: One hundred and thirty eight consecutive cirrhotic patients with HCC
      after curative resection are included. The correlations between serum AFP level
      and clinicopathological parameters and patient survival are evaluated and
      compared when 400ng/mL and 20ng/mL are set as cut-off points. RESULTS: Serum AFP
      level is associated with more clinicopathological variables of HCC under the cut
      off value of 400ng/mL, than that of 20ng/ mL. However, serum AFP level under the
      cut-off value of 20ng/mL is of significant prognostic impact for both overall and
      tumor-free survival, whereas that under 400ng/mL is not. CONCLUSIONS: The two cut
      off values of preoperative AFP levels might be of different implications in
      cirrhotic patients with HCC after curative resection. Therefore, these might be
      adopted differentially in HCC.

PMID- 22469730
TI  - Transverse hepatectomy: a 14-years experience.
AB  - BACKGROUND/AIMS: Transverse hepatectomy, removal of hepatic segments IVB, V, VI,
      (III) in continuity with the gallbladder through the transverse portal plane, was
      first introduced by Paul Sugarbaker in 1990. In 1995 the first transverse
      hepatectomy in Hungary was carried out by our workgroup. This article summarizes
      our experience with transverse hepatectomies during the period from 1995 to 2008.
      METHODOLOGY: During this time 72 trisegmentectomies were performed 22 out of
      these operations were transverse hepatectomies. RESULTS: The average resection
      time for transverse hepatectomy was 1 hour and 20 minutes, there was an average
      0.8 unit blood transfusion requirement per patient, the average exclusion time
      was 20.6 minutes, the average time spent in hospital postoperatively was 10.1
      days and there were 2 perioperative deaths due to sepsis and hemorrhagic shock.
      CONCLUSIONS: In our experience transverse hepatectomy proved to be a bloodless,
      relatively easy procedure, which enables safe removal of the antero-lateral
      segments. This new type of major hepatic resection is very useful in metastasis
      surgery and has minimal associated morbidity and mortality.

PMID- 22469731
TI  - Usefulness of omental wrapping to prevent biliary leakage and delayed gastric
      emptying in left hepatectomy.
AB  - BACKGROUND/AIMS: To identify the clinical significance of the omental wrapping
      (OW) technique after left hepatectomy to reduce bile leakage and delayed gastric
      emptying. We examined clinical and surgical parameters after left hepatectomy
      with or without biliary reconstruction in 79 patients. METHODOLOGY: This was a
      retrospective study of data from 14 patients undergoing OW compared to 65
      patients in the control group. RESULTS: Bile leakage and delayed emptying after
      hepatectomy were observed in 15 and 11 patients, respectively. Gender, background
      liver function, liver diseases and preoperative liver function tests were not
      significantly different between both groups. Prevalence of extent of hepatectomy,
      existence of segment 1 resection, biliary-enteric anastomosis, operating time and
      blood loss were also not significantly different between groups. Prevalence of
      bile leakage was similar between the OW and the control group (14 vs. 20%)
      (p=0.91). Prevalence of delayed gastric emptying was not significantly different
      between groups, but this complication was not observed in the OW group in
      comparison with the control group (0% vs. 20%) (p=0.31). Prevalence of other
      complications and hospital stay after hepatectomy were similar between groups.
      CONCLUSIONS: Significant differences for preventing left hepatectomy related
      complications were not found; however, it is possible that OW could reduce
      delayed gastric emptying.

PMID- 22469732
TI  - Successful case with hemophagocytic syndrome after living donor liver
      transplantation.
AB  - Hemophagocytic syndrome (HPS) is a rare but serious complication that is
      associated with hypercytokinemia caused by activated T lymphocytes and
      macrophages in immunologically compromised patients. Living donor liver
      transplantation (LDLT) between adults has been performed to compensate for the
      shortage of available organs. There have been some reports of HPS after LDLT but
      its prognosis is disappointingly poor. Herein, we report a case of HPS in a 53
      year-old woman who underwent LDLT using a left lobe graft. HPS was diagnosed on
      postoperative day 6 and successfully treated with a steroid pulse. HPS is a fatal
      complication in immunologically compromised patients but its early diagnosis and
      appropriate treatment can lead to an improved outcome.

PMID- 22469733
TI  - Hepatic parenchymal atrophy induction for intractable segmental bile duct injury
      after liver resection.
AB  - Liver resection can result in various types of bile duct injuries but their
      treatment is usually difficult and often leads to intractable clinical course. We
      present an unusual case of hepatic segment III duct (B3) injury, which occurred
      after left medial sectionectomy for large hepatocellular carcinoma and was
      incidentally detected 1 week later due to bile leak. Since the pattern of this B3
      injury was not adequate for operative biliary reconstruction, atrophy induction
      of the involved hepatic parenchyma was attempted. This treatment consisted of
      embolization of the segment III portal branch to inhibit bile production,
      induction of heavy adhesion at the bile leak site and clamping of the
      percutaneous transhepatic biliary drainage (PTBD) tube to accelerate segment III
      atrophy. This entire procedure, from liver resection to PTBD tube removal took 4
      months. This patient has shown no other complication or tumor recurrence for 4
      years to date. These findings suggest that percutaneous segmental portal vein
      embolization, followed by intentional clamping of external biliary drainage, can
      effectively control intractable bile leak from segmental bile duct injury.

PMID- 22469734
TI  - Treatment of rapid weight loss in a donor with hepatic steatosis in living donor
      liver transplantation: a case report.
AB  - The use of steatotic livers for transplantation is often associated with
      increased primary non-function. To reduce the risk of liver injury, steatosis of
      the donor liver in living donor liver transplantation (LDLT) was treated with
      restricted diet and exercise. A 21-year-old male donor, 167cm in height and 87kg
      in body weight, initially received a 1800kcal/day diet for 9 days which was then
      gradually reduced using a 1600kcal/day diet for 43 days, followed by a
      1500kcal/day diet for one day and was finally maintained on a 1400kcal/day diet
      for 52 days. Daily exercise consumed 500kcal/day. The non-protein respiratory
      quotient (npRQ) gradually increased while the non-esterified fatty acids (NEFA)
      decreased during the course of the 105-day treatment. Consequently, the initial
      80% steatosis was reduced to 10% and was accompanied by 13% weight loss for 81
      days. The npRQ values and NEFA concentrations in the later period of dietary and
      exercise treatment were higher and lower, respectively, than in the early
      treatment period, indicating compensation through long-term treatment. Therefore,
      energy metabolism and NEFA levels represent important biomarkers for short-term
      intensive treatment by restricted diet and exercise in donors with hepatic
      steatosis.

PMID- 22469735
TI  - Recurrent hepatocellular carcinoma with tumor thrombus in right atrium - report
      of a successful liver resection with tumor thrombectomy using total hepatic
      vascular exclusion without concomitant cardiopulmonary bypass.
AB  - For resection of advanced hepatocellular carcinoma (HCC) in which tumor thrombus
      (TT) extends into inferior vena cava (IVC) or right atrium (RA) surgery is
      challenging and requires skillful techniques. Here, we report a case of recurrent
      HCC with TT extending to the RA, who underwent successful resection with tumor
      thrombectomy without concomitant cardiopulmonary bypass. A 71-year-old man, who
      had been followed- up for hepatitis C by a local hospital, was diagnosed as
      having HCC in segment 6 for which he had undergone segmentectomy of segment 6 in
      May 2009. During follow-up, he developed severe leg edema and ascites with
      investigations revealing recurrent HCC in segment 7 with TT extending to the
      right atrium via IVC. After transarterial embolization the patient underwent
      extended resection of the segment 7 with tumor thrombectomy of the IVC and the
      right atrium and partial resection of the IVC wall using total hepatic vascular
      exclusion, without concomitant cardiopulmonary bypass. Total ischemic time was 23
      minutes, operation time was 6 hours and blood loss was 2,474mL. The postoperative
      course was uneventful. Histopathology was recurrent hepatocellular carcinoma with
      hepatic venous invasion. We report the case of resected recurrent HCC with TT
      extending to right atrium without concomitant cardiopulmonary bypass.

PMID- 22469736
TI  - Technique of antegrade intraoperative cholangiography not requiring hepatic hilar
      dissection during repeated hepatectomy for hepatocellular carcinoma.
AB  - It is important to perform intraoperative cholangiography (IOC) during liver
      resection in order to detect bile leaks, but its performance is not so simple
      during repeat hepatectomy. We describe the technique of antegrade intraoperative
      cholangiography not requiring hepatic hilar dissection during repeated
      hepatectomy. The patient was a 35-year-old female who had undergone 4 previous
      operations for hepatocellular carcinoma. During the fifth operation, it was not
      possible to dissect the hepatic hilum only for taking IOC because of heavy
      adhesion. A small-sized intrahepatic glissonian branch was isolated during
      parenchymal transection, which was later used for an infusion route of IOC. A 24
      gauge angiocatheter was inserted into the intrahepatic bile duct stump and tied
      over the whole glissonian pedicle stump. An IOC was successfully taken through
      this catheter and the glissonian pedicle stump was ligated after a leak test
      using methylene blue solution. At 32 months after this hepatectomy, she underwent
      deceased- donor liver transplantation due to hepatic failure from bile duct
      invasion by recurrent tumor. During recipient hepatectomy, previous minimal hilar
      dissection appeared very beneficial because some of the hilar structures remained
      undissected. This technique of antegrade IOC through the intrahepatic bile duct
      within the glissonian pedicle allows for an IOC without additional manipulation
      of the hepatoduodenal ligament when the cystic duct stump is not available.

PMID- 22469737
TI  - Cirrhosis should not be considered as an absolute contraindication for
      pancreatoduodenectomy.
AB  - BACKGROUND/AIMS: Liver cirrhosis is considered to be a contraindication for
      pancreaticoduodenectomy (PD). The aim of this study was to present 4 cases of
      successful PD in cirrhotic patients. METHODOLOGY: Among the charts of 90 patients
      who underwent PD between 2004 and 2008, 4 patients with liver cirrhosis were
      retrospectively reviewed. RESULTS: There were 3 males and 1 female, aged from 53
      to 66 years, who underwent PD for pancreatic head adenocarcinoma (n=3) or
      ampullary carcinoma (n=1). The median tumor size was 21mm (18-26) and 2 patients
      had preoperative biliary drainage. All patients had biopsy showing cancer prior
      to the operation. Cirrhosis was preoperatively suspected due to chronic
      alcoholism or liver dismorphy on CTscan and confirmed histologically in all
      patients. All patients were Child Pugh A without portal hypertension. The median
      operating time was 575 minutes (480-600) and 2 patients received an
      intraoperative blood transfusion. No patient died postoperatively. All patients
      had postoperative complications: ascites (n=2), pancreatic fistula (soft
      pancreas) (n=2) and pulmonary infection (n=1). There was neither liver failure
      nor postoperative bleeding. Two patients required re-operation for suspected
      mesenteric ischemia (n=1) and pancreatic fistula (n=1). The median length of
      hospitalization was 50 days (41-74). The median survival was 12.5 months (3
      patients are alive and disease free). CONCLUSIONS: Our data shows that PD in
      patients with Child A liver cirrhosis should not be systematically considered as
      a contraindication.

PMID- 22469738
TI  - Gastric marginal ulcer after pancreaticoduodenectomy with pancreaticogastrostomy
      due to delayed gastric emptying and Helicobacter pylori infection.
AB  - BACKGROUND/AIMS: Marginal ulceration and delayed gastric emptying are
      considerable problems after pancreaticoduodenectomy. Helicobacter pylori (HP) are
      well known to be associated with gastritis, gastric ulcer and gastric cancer.
      Thus, we studied the relationship between marginal ulceration and delayed gastric
      emptying in the early postoperative period after pancreaticoduodenectomy with
      pancreaticogastrostomy. METHODOLOGY: We retrospectively studied 58 patients who
      underwent pancreaticoduodenectomy with pancreaticogastrostomy. On the basis of
      the grade of delayed gastric emptying, these patients were divided into 2 groups
      WS group; without/with slight delayed gastric emptying and MS group;
      moderate/severe delayed gastric emptying. RESULTS: Two patients (3.4%) developed
      postoperative marginal ulcer, these 2 patients had no HP infection; moreover,
      they belonged to the MS group. Five patients in the WS group were infected with
      HP; although, postoperative marginal ulceration did not develop in these 5
      patients. CONCLUSIONS: Delayed gastric emptying might be a stronger promoting
      factor of postoperative marginal ulcer after pancreaticoduodenectomy with
      pancreaticogastrostomy rather than HP infection and prevention of delayed gastric
      emptying is important to reduce the occurrence rate of postoperative marginal
      ulcer. Our modified subtotal stomach-preserving pancreaticoduodenectomy is a
      useful procedure for preventing delayed gastric emptying and postoperative
      marginal ulcer after pancreaticoduodenectomy with pancreaticogastrostomy.

PMID- 22469739
TI  - Description of pylorus-preserving pancreaticoduodenectomy in elderly patients.
AB  - BACKGROUND/AIMS: The aim of this paper is to examine the safety and feasibility
      of pylorus-preserving pancreaticoduodenectomy in elderly patients. METHODOLOGY:
      The study population consisted of 40 consecutive patients. They were divided into
      two groups: Group A (<75 years old) and Group B (=75 years old). Reconstruction
      with a vertical duodenojejunostomy and internal pancreatic drainage with an
      omental wrapping was performed on the patients in both the groups. RESULTS: Less
      time was required to complete the operations in Group B (280+/-20min) than in
      Group A (386+/-88min; p=0.0006). Intraoperative blood loss in Group B was
      significantly lesser (365+/-109g) than that in Group A (629+/-249g; p=0.0026). No
      statistically significant difference was observed between both groups, in terms
      of the length of time required until food intake resumed and length of hospital
      stay. Although the rate of postoperative complication was higher in Group B
      (10.0%), no statistically significant difference was observed. CONCLUSIONS:
      Pylorus-preserving pancreaticoduodenectomy with a vertical duodenojejunostomy and
      internal pancreatic drainage with an omental wrapping seems safe and can be
      performed on elderly patients without a significant risk of complications.

PMID- 22469740
TI  - Total pancreatectomy for pancreatic carcinoma: evaluation of safety and efficacy.
AB  - BACKGROUND/AIMS: To determine the safety and the efficacy of total pancreatectomy
      for the curative treatment of pancreatic carcinoma. METHODOLOGY: Retrospective
      analysis was performed using 10 patients receiving total pancreatectomy. RESULTS:
      The median duration of the operative procedure was 8.7 hours and the median
      estimated blood loss was 2,700mL. Seven patients developed postoperative
      complications, including infections in 5 cases. There was no death associated
      with the operative procedure itself. Median period of postoperative hospital stay
      was 55 days. Anastomotic ulcer was prevented by administration of proton- pump
      inhibitors. Blood glucose level was well controlled by subcutaneous injection of
      sliding scale insulin during the postoperative period and the dosage of insulin
      required was 0.45+/-0.13units/kg body weight/ day at the time of discharge. The
      mean HbA1c level at 3 months after the operation was 6.1%. Four patients needed
      medication with anti-diarrheal drugs. CONCLUSIONS: Total pancreatectomy could be
      performed safely and postoperative daily performance was reasonable with
      effective medication. We suggest that total pancreatectomy should be considered
      for the treatment of pancreatic carcinoma when the patient status is appropriate
      for this procedure.

PMID- 22469741
TI  - Evaluation of surgical resection for pancreatic carcinoma at a Japanese single
      cancer institute.
AB  - BACKGROUND/AIMS: Surgical resection is a radical treatment option for pancreatic
      carcinoma (PC); however, it is still difficult to cure and patient prognosis is
      poor at this stage. METHODOLOGY: We examined the demographics, surgical records
      and outcome in 64 patients with hilar PC undergoing surgical resection. RESULTS:
      Pancreatoduodenectomy (PD) was carried out in 48 patients, distal pancreatectomy
      (DP) in 14 and total pancreatectomy in two. Postoperative complications were
      observed in 18 patients (28%) but no hospital deaths. All stage I patients showed
      carcinoma in situ of intraductal papillary mucinous carcinoma (IPMC).
      Postoperative adjuvant chemotherapy was performed in 15 patients (23%) using
      gemcitabine or S-1. Cancer recurrence was observed in 36 patients (56%) and 31
      died of carcinoma. The 5-year cancer-free and overall survival rate was 12% and
      14%, respectively. CA19-9 level, morphological type, T category, lymph node
      metastasis, extrapancreatic nerve plexus invasion, retropancreatic tissue
      invasion, distal bile duct invasion, duodenal invasion and arterial system
      invasion were significant poor prognostic factors; however, portal vein system
      invasion was not significantly associated with prognosis. Cancer infiltration at
      bile duct cut-end and dissected peripancreatic tissue margin and presence of
      residual tumor showed a poor prognosis. Surgical prognosis in only non-invasive
      IPMC was satisfactory. CONCLUSIONS: Radically extended surgical resection is
      necessary and newly effective adjuvant chemotherapy is a promising modality to
      improve patient survival in PC patients.

PMID- 22469742
TI  - Prognostic predictors of patients with carcinoma of the gastric cardia.
AB  - BACKGROUND/AIMS: This study gives insight into survival predictors and
      clinicopathological features of carcinoma of the gastric cardia. METHODOLOGY: The
      study included 233 patients who underwent operation for carcinoma of the gastric
      cardia. Clinicopathological prognostic variables were evaluated as predictors of
      long-term survival by univariate and multivariate analysis. Cox regression was
      used for multivariate analysis and survival curves were drawn by the Kaplan-
      Meier method. RESULTS: Carcinoma of the gastric cardia was characterized by
      positive lymph node metastasis (77.3%), serosal invasion (83.3%) and more stage
      III or IV tumors (72.5%). Overall 5-year survival rate was 21.9% and median
      survival period was 24 months. The 5-year survival rate was influenced by tumor
      size, depth on invasion, lymph node metastasis, extent of lymph node dissection,
      disease stage, operation methods and resection margin. CONCLUSIONS: The absent of
      serosal invasion and lymph node metastasis, curative resection should be
      considered to be the favourable predictors of long-term survival of patients with
      carcinoma of the gastric cardia.

PMID- 22469743
TI  - Biopsy from the base and edge of gastric ulcer healing or complete healing may
      lead to detection of gastric cancer earlier: an 8 years endoscopic follow-up
      study.
AB  - BACKGROUND/AIMS: To assess the incidence of gastric cancer development in gastric
      benign ulcer patients and to evaluate the value of biopsy by taking specimens
      from both the base and edges of ulcers in contrast to the traditional biopsy
      which takes specimens from the edges of ulcers only. METHODOLOGY: An endoscopic
      followup of more than 1 year was conducted on 456 gastric ulcer patients in our
      hospital for a duration over 8 years. We collected clinical, endoscopic and
      pathological data and obtained at least 6 biopsies from both the edges and the
      bases of ulcers healing or complete healing, respectively and assessed H. pylori
      infection. RESULTS: Gastric cancers developed in 11 (2.41%) of 456 GU patients.
      In the experimental group, 3 cases that were diagnosed by histology showed
      adenocarcinoma with specimens taken from the ulcer bases and in the other 5 cases
      the specimens were taken from the ulcer edges. The detection rate of gastric
      cancer from gastric ulcer between experimental group and control group was
      statistically significant (4.57% vs. 1.07%, p<0.05). CONCLUSIONS: Gastric ulcer
      may develop into gastric cancer over a certain period of time in patients
      infected with H. pylori. Biopsies from ulcer bases and edges at the second or
      subsequent endoscopies may lead to defection of gastric cancer earlier and more
      effectively than the biopsies which take specimens from the edges of ulcers only.

PMID- 22469744
TI  - Radical endoscopic resection is unsuitable for most synchronous, multiple and
      early gastric cancers.
AB  - BACKGROUND/AIMS: It remains unclear whether synchronous, multiple, early gastric
      cancers can be radically resected with endoscopic resection. METHODOLOGY:
      Patients who underwent gastrectomy for early gastric cancer were included in this
      study and divided into two groups: a solitary gastric cancer group and a multiple
      gastric cancer group. The clinicopathological features of patients in each group
      were compared and the criteria for endoscopic resection were subsequently
      investigated. RESULTS: A total of 244 patients were included in the present
      study. The solitary and multiple gastric cancer groups included 228 patients
      (93.4%) and 16 patients (6.6%), respectively. The multiple gastric cancer group
      included 35 lesions, including a greater number of larger tumors and protruded-
      type tumors, as well as increased incidence of submucosal and lymphatic invasion.
      Only 2 of 16 cases (12.5%) in the multiple gastric cancer group met the criteria
      for endoscopic resection. Eleven cases were excluded due to submucosal invasion
      and three cases were excluded due to undifferentiated histopathological type
      tumors. CONCLUSIONS: To be suitable for radical endoscopic resection, prompt
      detection of early gastric cancer is essential, before they become multiple
      gastric cancers and invade the submucosa.

PMID- 22469745
TI  - Quercetin suppresses NF-kappaB and MCP-1 expression in a high glucose-induced
      human mesangial cell proliferation model.
AB  - Diabetic nephropathy (DN), which is characterized by mesangial cell
      proliferation, is a common complication observed in diabetic patients. The
      protective effects of quercetin for DN have been reported; however, the mechanism
      has yet to be determined. We aimed to identify the underlying mechanism for
      quercetin protection against DN. High glucose (HG)-induced human mesangial cell
      (HMC) proliferation, a feature of the early stages of diabetic nephropathy, was
      employed as an in vitro model. Cells were grown in normal glucose (5.6 mM), high
      glucose (30 mM) or high glucose with various concentrations of quercetin. Cell
      proliferation, cell cycle progression, and expression of NF-kappaB and MCP-1 were
      examined by MTT assay, DNA staining, immunocytochemistry and western blot
      analysis, respectively. HMCs cultured in high glucose had signficantly greater
      proliferation, accumulation in the G1 phase, upregulated NF-kappaB and MCP-1
      expression. Quercetin treatment reversed the effects of high glucose in a dose
      dependent manner. Cotreatment of quercetin with pyrrolidine dithiocarbamate
      (PDTC), an inhibitor of NF-kappaB activation, suggest that the effects of
      quercetin are partially mediated by NF-kappaB signaling. Quercetin partially
      suppresses the effects of high glucose in HMC cultures, which are mediated at
      least in part through the suppression of NF-kappaB.

PMID- 22469746
TI  - Association between polymorphisms of the DNA base excision repair genes MUTYH and
      hOGG1 and age-related macular degeneration.
AB  - Age-Related Macular Degeneration (AMD) is an eye disease that results in
      progressive and irreversible loss of central vision and is considered as the
      primary cause of visual impairment, including blindness, in the elderly in
      industrialized countries. Oxidative stress has been implicated in the
      pathogenesis of AMD. The hOGG1 and the MUTYH genes play an important role in the
      repair of oxidatively damaged DNA in the base excision repair pathway. The DNA
      glycosylases encoded by the hOGG1 and MUTYH genes initiate this pathway by
      recognizing and removing 8-oxoguanine and adenine paired with 8-oxoguanine,
      respectively. Our study was designed to examine the association between the
      c.977C>G polymorphism (rs1052133) of the hOGG1 gene and the c.972G>C polymorphism
      (rs3219489) of the MUTYH gene and AMD as well as the modulation of this
      association by some clinical and lifestyle factors. Genotypes were determined in
      DNA from blood of 271 AMD patients, including 101 with wet and 170 with dry form
      of the disease and 105 sex- and age-matched individuals without AMD. We observed
      an association between AMD, dry and wet forms of AMD and the C/G genotype and the
      G allele of the c.977C>G-hOGG1 polymorphism (p 0.006; 0.009; 0.021 and 0.004;
      0.005; 0.016 respectively). On the other hand, the C/C genotype and the C allele
      reduced the risk of AMD as well as of its dry form or wet form (p 0.002; 0.003;
      0.010 and 0.004; 0.005; 0.016, respectively). Therefore, the associations we
      detected were driven by the dry AMD. We observed some statistically significant
      association between the occurrence of AMD and its dry and wet forms and genotypes
      of the other polymorphism, the c.972G>C-MUTYH polymorphism, but due to borderline
      character of all this association we do not consider them as medically relevant.
      Our findings suggest that the c.977C>G-hOGG1 polymorphism may be associated with
      dry AMD. Further studies are needed to determine possible association between AMD
      and the c.972G>C-MUTYH polymorphism.

PMID- 22469747
TI  - Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in
      long-term potentiation in rat medial prefrontal cortex.
AB  - Epigenetic mechanisms have recently been known to play fundamental roles in the
      regulation of synaptic plasticity, and learning and memory tasks in many brain
      regions, such as the hippocampus, the amygdala, the insular cortex. However,
      epigenetic mechanism in the medial prefrontal cortex (mPFC), also a crucial
      neural locus for the control of cognition and emotion, is not well known. The
      present study investigated the epigenetic regulation of two genes, reelin and
      brain-derived neurotrophic factor (bdnf), both play important roles in neural
      plasticity, in the mPFC. The data showed that the levels of total DNA
      methyltransferase (DNMTs), total histone acetyltransferases (HATs), global
      acetylated histone 3 (H3) and global acetylated histone 4 (H4) were all changed
      with the induction of long-term potentiation (LTP) in the mPFC, implying that DNA
      methylation and histone acetylation may involve in synaptic plasticity in the
      mPFC. The present results further demonstrated that the demethylation status of
      reelin and bdnf, and acetylated H3 and acetylated H4 at the reelin and the bdnf
      promoters in the mPFC were enhanced by the delivery of LTP-inducing high
      frequency stimulation (HFS). Consistently, infusion of DNMT inhibitor, 5
      azacytidine (5-azaC), or histone deacetylases (HDACs) inhibitor, sodium butyrate
      (NaB), into the mPFC could interfere with LTP-associated demethylation and
      acetylation of reelin and bdnf genes, and the induction of LTP as well. Long-term
      retention of trace fear memory, which is dependent on mPFC function, was also
      altered by administration of these inhibitors into the mPFC. These findings
      suggest that epigenetic regulation of DNA demethylation and histone acetylation
      of target genes, such as reelin and bdnf, might underlie the mechanisms of
      synaptic plasticity and memory retention in the mPFC.

PMID- 22469748
TI  - Trace and contextual fear conditioning are impaired following unilateral
      microinjection of muscimol in the ventral hippocampus or amygdala, but not the
      medial prefrontal cortex.
AB  - Trace fear conditioning, in which a brief empty "trace interval" occurs between
      presentation of the CS and UCS, differs from standard delay conditioning in that
      contributions from both the hippocampus and prelimbic medial prefrontal cortex
      (PL mPFC) are required to form a normal long term memory. Little is currently
      known about how the PL interacts with various temporal lobe structures to support
      learning across this temporal gap between stimuli. We temporarily inactivated PL
      along with either ventral hippocampus or amygdala in a disconnection design to
      determine if these structures functionally interact to acquire trace fear
      conditioning. Disconnection (contralateral injections) of the PL with either the
      ventral hippocampus or amygdala impaired trace fear conditioning; however,
      ipsilateral control rats were also impaired. Follow-up experiments examined the
      effects of unilateral inactivation of the PL, ventral hippocampus, or amygdala
      during conditioning. The results of this study demonstrate that unilateral
      inactivation of the ventral hippocampus or amygdala impairs memory, while
      bilateral inactivation of the PL is required to produce a deficit. Memory
      deficits after unilateral inactivation of the ventral hippocampus or amygdala
      prevent us from determining whether the mPFC functionally interacts with the
      medial temporal lobe using a disconnection approach. Nonetheless, our findings
      suggest that the trace fear network is more integrated than previously thought.

PMID- 22469750
TI  - Pediatric ECPR: standard of care?

PMID- 22469749
TI  - Roles of nucleus accumbens and basolateral amygdala in autoshaped lever pressing.
AB  - Initially-neutral cues paired with rewards are thought to acquire motivational
      significance, as if the incentive motivational value of the reward is transferred
      to the cue. Such cues may serve as secondary reinforcers to establish new
      learning, modulate the performance of instrumental action (Pavlovian-instrumental
      transfer, PIT), and be the targets of approach and other cue-directed behaviors.
      Here we examined the effects of lesions of the ventral striatal nucleus accumbens
      (ACb) and the basolateral amygdala (BLA) on the acquisition of discriminative
      autoshaped lever-pressing in rats. Insertion of one lever into the experimental
      chamber was reinforced by sucrose delivery, but insertion of another lever was
      not reinforced. Although sucrose was delivered independently of the rats'
      behavior, sham-lesioned rats rapidly came to press the reinforced but not the
      nonreinforced lever. Bilateral ACb lesions impaired the initial acquisition of
      sign-tracking but not its terminal levels. In contrast, BLA lesions produced
      substantial deficits in terminal levels of sign-tracking. Furthermore, whereas
      ACb lesions primarily affected the probability of lever press responses, BLA
      lesions mostly affected the rate of responding once it occurred. Finally,
      disconnection lesions that disrupted communication between ACb and BLA produced
      both sets of deficits. We suggest that ACb is important for initial acquisition
      of consummatory-like responses that incorporate hedonic aspects of the reward,
      while BLA serves to enhance such incentive salience once it is acquired.

PMID- 22469751
TI  - A comparison of survival with and without extracorporeal life support treatment
      for severe poisoning due to drug intoxication.
AB  - BACKGROUND: The use of extracorporeal life support (ECLS) as a treatment for
      severe cardiovascular impairment due to poisoning is unclear. Therefore, we
      conducted a retrospective cohort analysis to compare survival among critically
      ill poisoned patients treated with or without ECLS. METHODS: All consecutive
      patients admitted into 2 university hospitals in northwestern France over the
      past decade for persistent cardiac arrest or severe shock following poisoning due
      to drug intoxication were included. ECLS was preferentially performed in 1 of the
      2 centers. RESULTS: Sixty-two patients (39 women, 23 men; mean age 48+/-17 years)
      fulfilled inclusion criteria: 10 with persistent cardiac arrest and 42 with
      severe shock. Fourteen patients were treated with ECLS and 48 patients with
      conventional therapies. All subjects received vasopressor and fluid loading.
      Patients treated with or without ECLS at ICU admission had comparable drug
      ingestion histories, Simplified Acute Physiology Score (SAPS II score) (66+/-18),
      Sequential Organ Failure Assessment (SOFA) score (median: 11 [IQR, 9-13]),
      Glasgow Coma Scale score (median: 3 [IQR, 3-11]), need for ventilator support
      (n=56) and extra renal support (n=23). Thirty-five (56%) patients survived: 12/14
      (86%) ECLS patients and 23/48 (48%) non-ECLS patients (p=0.02, by Fisher exact
      test). None of the patients with persistent cardiac arrest survived without ECLS
      support. Based on admission data, beta-blocker intoxication (p=0.02) was also
      associated with lower mortality. In multivariate analysis, adjusting for SAPS II
      and beta-blocker intoxication, ECLS support remained associated with lower
      mortality [Adjusted Odds Ratio, 0.18; 95% CI, 0.03-0.96; p=0.04]. CONCLUSION: In
      the absence of response to conventional therapies, we consider that ECLS may
      improve survival in critically ill poisoned patients experiencing cardiac arrest
      and severe shock.

PMID- 22469752
TI  - Current world literature.

PMID- 22469754
TI  - Effects of palmitoylethanolamide on intestinal injury and inflammation caused by
      ischemia-reperfusion in mice.
AB  - Our primary aim in this study was to test the hypothesis that PEA, a member of
      the fatty acid ethanolamide family and an endogenous PPAR-alpha ligand, exerts
      anti-inflammatory effects on SAO shock, causing a severe form of circulatory
      shock and enhanced formation of ROS. SAO shock was induced by clamping the
      superior mesenteric artery and the celiac trunk, resulting in a total occlusion
      of these arteries for 30 min. After this period of occlusion, the clamps were
      removed. In this study, we demonstrated that the administration of PEA, 5 min
      before reperfusion, significantly reduced all of the parameters involved during
      inflammation, such as proinflammatory cytokine production (TNF-alpha, IL-1beta),
      adhesion molecules (ICAM-1, P-selectin) expression, NF-kappaB expression, and
      apoptosis (Bax, Bcl-2, TUNEL assay) activation. In addition, to study whether the
      protective action of PEA on SAO shock is also related to the activation of PPAR
      alpha, we have investigated the effect of PEA in PPAR-alpha KO mice subjected to
      SAO shock. Our study clearly demonstrates that PEA significantly attenuated the
      degree of intestinal injury and inflammation caused by I/R injury. Moreover, the
      positive effects of PEA were at least in part dependent on the PPAR-alpha
      pathway. The results clearly indicate that PEA exerts an anti-inflammatory
      effect, also in a SAO shock model, which could imply a future use of PEA in the
      treatment of I/R shock.

PMID- 22469757
TI  - From the Editor-in-Chief: lead us not into the temptation to text.

PMID- 22469755
TI  - T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in
      the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells.
AB  - T-type voltage-gated Ca2+ channels have unique electrophysiological properties,
      suitable for generating Ca2+ oscillations and waves and thus controlling the
      proliferation of various tumor cells. In the present study, we investigated the
      role of Cav3.1, a candidate tumor suppressor gene, in neoplastic processes, and
      compared the differences between Cav3.1 with Cav3.2 channels. While the
      overexpression of a full-length Cav3.1 clone suppressed cell proliferation, the
      knockdown of the Cav3.1 gene by siRNA, or treatment with ProTx-I, a relatively
      selective inhibitor for Cav3.1, promoted the cell proliferation of MCF-7 cells (a
      human breast adenocarcinoma cell line). Although Cav3.1 and Cav3.2 channels
      possess comparable biophysical properties and are often co-expressed in various
      tissues, gene knockdown or the overexpression of Cav3.2 channels exhibited no
      effect on cell proliferation. Using immunocytochemical co-staining, the Cav3.1
      channels were specifically visualized in the plasma membranes of apoptotic cells,
      identified by Annexin V and terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) assays and nuclear condensation. On the contrary, Cav3.2
      channels were expressed at the membrane of large portions of cells, with no
      likely relation to Cav3.1 expression or apoptosis. An apoptosis assay revealed
      that the overexpression of the Cav3.1 clone caused an increase in the number of
      apoptotic cells. Furthermore, Cav3.1 knockdown blocked cyclophosphamide-induced
      apoptosis. These results suggest that Cav3.1 channels may contribute to the
      repression of tumor proliferation and the promotion of apoptosis mediated via
      Cav3.1-specific Ca2+ influx.

PMID- 22469758
TI  - Exploring nurses' perceptions of collecting and using HOBIC measures to guide
      clinical practice and improve care.
AB  - Ontario's Health Outcomes for Better Information and Care (HOBIC) is designed to
      help organizations and nurses plan and evaluate care by comparing patient
      outcomes with historical data on similar cases. Yet, fewer than 15% of patients
      in a 2010 study were found to have complete admission and discharge data sets.
      This low utilization rate of HOBIC measures prompted the current qualitative
      study, in which nurses from three clinical settings in an academic teaching
      hospital were interviewed to gain their perceptions related to collecting and
      using HOBIC measures in practice. The objective was to identify factors that
      promote or impede the collection and use of HOBIC data in clinical practice to
      improve patient care and outcomes. Analysis of interview results produced four
      key themes related to (a) use of HOBIC measures to inform patient care, (b)
      collecting and documenting HOBIC measures, (c) HOBIC as an afterthought and
      "black hole" and (d) impediments to assessing and documenting HOBIC measures
      because of language barriers, patients' cognitive status and lack of time.
      Recommendations to improve uptake include developing, implementing and evaluating
      a communication and learning plan that promotes HOBIC's values and benefits, and
      determining how managers and administrators perceive utilization of HOBIC at the
      clinical unit and organizational levels.

PMID- 22469759
TI  - "The potential is unlimited!" Nurse leader perspectives on the integration of
      HOBIC in Ontario.
AB  - Nurse leaders from a sample of acute care and long-term care sites participating
      in the Health Outcomes for Better Information and Care program in Ontario
      provided information on their experiences with HOBIC implementation. In addition,
      they described strategies to enhance successful implementation of the program.
      Finally, they discussed the potential future uses they envisioned for healthcare
      settings from the HOBIC data. Organizational benefits, such as data
      comparability, effective patient care planning and delivery and enhancement of
      nurses' technology skills were identified. Challenges that were highlighted
      included attaining buy-in from staff nurses, integration of HOBIC into existing
      computer systems and the subsequent computer and information technology
      challenges related to implementing such a program. Additional education and
      support for nursing staff and management were suggested as approaches for
      overcoming barriers. This survey demonstrates interest and commitment to HOBIC
      from many nurse leaders in Ontario and highlights the value that such a program
      provides for staff nurses in the planning and implementation of care. Nurse
      leaders in Ontario are keenly aware of the important potential that HOBIC data
      can provide for high-quality patient care and have identified key factors that
      need to be considered with the implementation of such a program.

PMID- 22469760
TI  - C-HOBIC: standardized clinical outcomes to support evidence-informed nursing
      care.

PMID- 22469761
TI  - Confirming what we've always known: nurses make a difference.

PMID- 22469762
TI  - Nursing residency program: a solution to introduce new grads into critical care
      more safely while improving accessibility to services.
AB  - PURPOSE: Critical care units are particularly affected by the shortage of nurses.
      In order to overcome this problem, many organizations have increased the hiring
      of newly graduated nurses. This paper describes a residency program developed to
      facilitate the safe integration of those nurses into critical care and its
      outcomes. METHODS: A one-year nursing residency program dedicated to nurses with
      less than a year of experience was implemented in 2008. Recruitment and retention
      rates, as well as accessibility to critical care, were evaluated. RESULTS: A 46%
      increase in recruitment rate of newly graduated nurses was observed when
      comparing the same period of time before and after implementation of the program.
      Moreover, the one-year retention rate rose by 26%; the retention rate, without
      considering the time since the beginning of employment, rose by 71%. As for
      accessibility to critical care, it increased by 50% (from 24 to 36 beds).
      Finally, the program was favourably evaluated by experienced nurses in terms of
      skills and critical thinking development among nursing residents. CONCLUSION: A
      nursing residency program developed to meet the needs of inexperienced nurses and
      integrate them into high-acuity settings appears to be one solution to resolving
      undesirable limited access to safe-quality critical care.

PMID- 22469763
TI  - Canadian oncology nurse work environments: part II.
AB  - In the aftermath of healthcare restructuring, it is important to pay attention to
      nurses' perceptions of workplace and professional practice factors that attract
      nurses and influence their retention. Continuing constraints on cancer care
      systems make the issue of health human resources an ongoing priority. This paper
      presents the findings of a follow-up study of a cohort of Canadian oncology
      nurses that aimed to compare nurses' perceptions of their work environment, job
      satisfaction and retention over a two-year period. Participants of the follow-up
      survey represented 65% (397/615) of the initial cohort. Many similar perceptions
      about the work environment were found over two years; however, at follow-up a
      larger proportion of nurses reported an absence of enough RNs to provide quality
      care and a lack of support for innovative ideas. With respect to career status,
      only 6% (25/397) of the follow-up sample had left oncology nursing. However, the
      proportion of nurses declaring an intention to leave their current job increased
      from 6.4% (39/615) on the initial survey to 26% (102/397) on the follow-up
      survey. Findings suggest that decision-makers need to use both the growing body
      of workplace knowledge and the input from staff nurses to implement changes that
      positively influence nurse recruitment and retention. Future research should
      focus on the implementation and evaluation of strategies that address workplace
      issues such as nurse staffing adequacy, leadership and organizational commitment.

PMID- 22469764
TI  - "Stop the noise!" From voice to silence.
AB  - Nurses are frequently portrayed in the literature as being silent about ethical
      concerns that arise in their practice. This silence is often represented as a
      lack of voice. However, in our study, we found that nurses who responded to
      questions about moral distress were not so much silent as silenced. These nurses
      were enacting their moral agency by engaging in diverse, multiple and time
      consuming actions in response to situations identified as morally distressing
      with families, colleagues, physicians, educators or managers. In many situations,
      they took action by contacting other healthcare team members, making referrals
      and coordinating care with other departments such as home care and hospice, as
      well as initiating contact with groups such as professional regulatory bodies or
      unions. Examining the relationship between ethical climate, moral distress and
      voice offers insights into both the meaning and impact of being silenced in the
      workplace.

PMID- 22469765
TI  - Gold mesoflower arrays with sub-10 nm intraparticle gaps for highly sensitive and
      repeatable surface enhanced Raman spectroscopy.
AB  - Self-assembling Au mesoflower arrays are prepared using a polymethylmethacrylate
      (PMMA) template on an iron substrate via a combined top-down/bottom-up
      nanofabrication strategy. The PMMA template with the holes around 300-500 nm in
      diameter is first fabricated by using polymer blend lithography on iron
      substrates, and the highly homogeneous Au mesoflower arrays with less than 10 nm
      intraparticle gaps are subsequently obtained by an in situ galvanic reaction
      between HAuCl4 solution and the iron substrate under optimal stirring of the
      solution as well as reaction time. Owing to the unique mesostructures and
      uniformity, Raman measurements show that the gold mesoflower arrays obtained
      demonstrated a strong and reproducible surface enhanced Raman scattering (SERS)
      enhancement on the order of ~10(7)-10(8). The development of a SERS substrate
      based on the Au mesoflowers with high spatial density of hot spots, relatively
      low cost and facial synthesis provides a novel strategy for applications in
      chemical and biomolecular sensing.

PMID- 22469767
TI  - Neuropharmacological study of Dracocephalum moldavica L. (Lamiaceae) in mice:
      sedative effect and chemical analysis of an aqueous extract.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dracocephalum moldavica is used as a tranquilizer
      and as remedy for nervous conditions relief in the Mexican traditional medicine.
      Despite its intensive use no literature reported neuropharmacological studies on
      Dracocephalum moldavica as yet. AIM OF THE STUDY: The sedative, anxiolytic-like
      and antidepressant-like effects of the aqueous extract of aerial parts of
      Dracocephalum moldavica (Lamiaceae) (DM) were evaluated in behavioral models in
      mice. The general toxic effects of DM were evaluated as well as their chemical
      analysis was performed. MATERIALS AND METHODS: DM effects were evaluated on
      pentobarbital-induced sleeping time (SPT), the hole-board (HBT), and the
      avoidance exploratory behavior (AEBT) tests and on the forced swimming test
      (FST). General activity and motor coordination were evaluated in the open field
      (OFT) and Rota-rod tests, respectively. The acute toxicity of DM was determinate
      by its LD(50) dose. The chemical analyses DM were performed by chromatographic
      and HPLC-ESI-MS techniques. RESULTS: DM prolonged the pentobarbital-induced
      sleeping time, induced sedation in the HBT, decreased spontaneous activity and
      produced motor coordination impairment in mice. However, DM did not show
      anxiolytic effects in the AEBT or HBT and it was not effective in FST. The DM
      treatment produced mortalities with LD(50)=470 mg/kg body weight. The HPLC-ESI-MS
      analysis of DM revealed that (acacetin, apigenin and luteolin)-7-O-beta-D-(6"-O
      malonyl)-glucoside derivates are the main compounds of DM. CONCLUSIONS: DM
      induced sedative actions and a general inhibition of CNS activity observed by the
      decrease of animals' general activity, motor coordination and exploration.

PMID- 22469768
TI  - The effects of Polygonum cuspidatum extract on wound healing in rats.
AB  - AIM OF THE STUDY: Polygonum cuspidatum has long been used as a traditional
      medicine inducing wound healing. In this study, the extract from the Chinese
      medicinal herb Polygonum cuspidatum was investigated on its wound healing
      activity, in order to obtain an accurate elucidation of its traditional use
      value. MATERIALS AND METHODS: After creating wound healing model on the back of
      rats, the extract from the Chinese medicinal herb Polygonum cuspidatum was
      applied. Wound healing rates were calculated at 3, 7, 14, and 21 days after the
      wounding, and tissues were harvested at 1, 3, 7, 14 and 21 days for histological
      and immunohistochemistry analysis. The stages of wound granulation tissues were
      evaluated histopathologically. The expression of TGF-beta1 was determined by
      immunohistochemically. RESULTS: Wound healing rates were significantly higher at
      3, 7, 14 and 21 days in the extract group than in the control (p<0.05).
      Histological results showed more well-organized bands of collagen, more
      fibroblasts and hair follicle and less inflammatory cells in the extract group.
      The immunohistochemical results revealed that TGF-beta1 increased in the extract
      group on day 1, 3 and 7 post-wounding (p<0.05). CONCLUSION: The present study has
      shown that the extract from the Chinese medicinal herb Polygonum cuspidatum
      possesses wound healing activity, and thus provided the evidence for its
      traditional use value.

PMID- 22469769
TI  - Screening of Brazilian medicinal plants for antiviral activity against rotavirus.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Brazilian medicinal plants traditionally used for
      the treatment of diarrhoea were investigated for their in vitro antiviral
      activity against the simian rotavirus SA11. MATERIALS AND METHODS: The ethanolic
      crude extracts of plants collected in the cerrado of Minas Gerais, Brazil were
      submitted to phytochemical screening. The cytotoxicity of the extracts was
      inferred by cellular morphologic alterations. Antiviral activity was assessed by
      the ability of the extracts to inhibit the cytopathic effect (CPE) of rotavirus
      on the treated cells. RT-PCR was performed to confirm and/or confront antiviral
      assay data. RESULTS: The maximum non-toxic concentration ranged from 50 to 500
      MUg/mL. All extracts were toxic at a concentration of 5000 MUg/mL but no extract
      showed cytotoxicity at 50 MUg/mL. The species Byrsonima verbascifolia,
      Myracrodruon urundeuva, Eugenia dysenterica and Hymenaea courbaril exhibited the
      strongest in vitro activity against rotavirus. Their extracts prevented the
      formation of CPE, and RT-PCR analysis detected no amplification of genetic
      material from rotavirus. Tannins, flavonoids, saponins, coumarins and terpenes
      were the major classes of natural products found in the leaf extracts that showed
      antiviral activity. CONCLUSION: Among the species studied, Byrsonima
      verbascifolia, Eugenia dysenterica, Hymenaea courbaril and Myracrodruon urundeuva
      showed potential activity against rotavirus and are worthy of further study. The
      present study corroborates ethnopharmacological data as a valuable source in the
      selection of plants with antiviral activity and to some extent validates their
      traditional uses.

PMID- 22469770
TI  - Panax quinquefolium saponins inhibited immune maturation of human monocyte
      derived dendritic cells via blocking nuclear factor-kappaB pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolium saponins (PQS), a water
      soluble antioxidant extracted from a natural herb, radix panacis quinquefolii
      (American Ginseng), has yielded encouraging results in the treatment of
      atherosclerotic diseases. However, the underlying mechanisms remain unclear.
      Here, we tested the hypothesis that the anti-atherosclerotic effect of PQS might
      be mediated by suppressing human monocyte-derived dendritic cells (DCs)
      maturation. MATERIALS AND METHODS: DCs were derived by incubating purified human
      monocytes with granulocyte macrophage colony stimulating factor (GM-CSF) and IL
      4. DCs were pre-incubated with or without PQS and stimulated by oxidized low
      density lipoprotein (ox-LDL). Expression of DCs membrane molecules (CD40, CD86,
      CD1a, HLA-DR) and endocytotic ability were analyzed by FACS, cytokines (IL-12 and
      TNF-alpha) were measured by ELISA. Nuclear factor (NF)-kappaB signaling pathway
      was determined by Western blotting, and RT-PCR. NF-kappaB activation was
      quantified by ELISA. RESULTS: PQS reduced ox-LDL induced immunophenotypic
      expressions (CD40, CD1a, CD86, and HLA-DR) and cytokine secretions (IL-12 and TNF
      alpha), and improved endocytotic ability of DCs. These above phenomena were
      accompanied by decreased protein expression and binding activity of nuclear
      localized c-Rel subunit. CONCLUSIONS: Our study suggested that PQS inhibited ox
      LDL induced immune maturation of DCs in vitro, which might be in part mediated by
      NF-kappaB signal transduction pathway.

PMID- 22469771
TI  - Renal protective effect of Rosa laevigata Michx. by the inhibition of oxidative
      stress in streptozotocin-induced diabetic rats.
AB  - Diabetic nephropathy (DN) is a long-term complication of diabetic mellitus.
      Numerous reports have suggested that oxidative stress is defined as the excessive
      production of reactive oxygen species (ROS) surpassing existing anti-oxidative
      defense mechanisms, and plays a critical role in the pathogenesis of diabetic
      nephropathy. Rosa laevigata Michx. (RLM) is the commonly used traditional Chinese
      medicine for the treatment of chronic urinary tract infections and anti-oxidative
      treatments, and has been shown to have a renal protective effect in diabetic
      rats. In the present study, we further investigate the effects of RLM on
      oxidative stress in the kidneys of streptozotocin-induced diabetic rats with DN.
      Our results suggest that RLM significantly ameliorates renal dysfunction in
      diabetic rats. The protection against the development of DN by RLM treatment
      involves increasing the activity of superoxide dismutase and total anti-oxidant
      capacity, decreasing the levels of malondialdehyde and ROS, and inhibiting the
      expression of nuclear factor-kappaB p65 and monocyte chemoattractant protein-1 at
      both the protein and mRNA levels with a concomitant increase in the expression of
      the IkappaBalpha protein. These results highlight the potential therapeutic
      application of RLM for the treatment of DN.

PMID- 22469772
TI  - Gait characteristics of individuals with transtibial amputations walking on a
      destabilizing rock surface.
AB  - Individuals with transtibial amputation (TTA) have a high incidence of falls
      during walking. Environmental factors, such as uneven ground, often play a
      contributing role in these falls. The purpose of this study was to quantify the
      adaptations TTA made when walking on a destabilizing loose rock surface. In this
      study, 13 young TTA walked over a rock surface and level ground at four
      controlled speeds. Subjects successfully traversed the rock surface by adopting a
      conservative gait characterized by shorter and wider steps. They also took
      shorter steps with their prosthetic limbs and exhibited greater variability in
      foot placement when stepping onto their intact limb. Between-limb differences in
      step length and width variability increased at faster walking speeds. TTA
      increased hip and knee flexion during initial stance, which contributed lowering
      the whole-body center of mass. TTA also increased hip and knee flexion during
      swing, enabling them to significantly increase their toe clearance on the rock
      surface compared to level ground. Toe clearance on the prosthetic side was aided
      by increased ipsilateral hip flexion. The results suggest that TTA were able to
      adapt their gait to overcome the challenge imposed by the rock surface. These
      adaptations were asymmetric and initiated proximally.

PMID- 22469773
TI  - Longitudinal changes in knee joint biomechanics during level walking following
      anterior cruciate ligament reconstruction surgery.
AB  - Following anterior cruciate ligament reconstruction (ACL) patients have altered
      movement patterns in the reconstructed knee during walking. There is limited
      information about these alterations over an extended period of time. This study
      was designed to present a longitudinal analysis of gait patterns following ACL
      reconstruction surgery. Assessments of level walking were undertaken in 16
      participants at a mean 10 months (initial assessment) and again at 3 years
      (follow-up assessment) after ACL reconstruction surgery. Kinematic and kinetic
      variables were analysed using a two factor (time, limb) repeated measures ANOVA.
      Kinematic data showed that patients were able to achieve greater extension about
      the reconstructed knee at follow-up than at initial assessment. The reconstructed
      knee was significantly less internally rotated than the contralateral knee at the
      initial assessment but not at follow-up. Kinetic data showed a significant
      increase in the external knee extension moment for the reconstructed limb over
      time. There were also significant increases in the external knee adduction moment
      for both limbs at the follow-up assessment. The external knee adduction moment
      was however smaller in the reconstructed knee than the contralateral knee at both
      assessments. The results indicate that gait variables do change over time and
      that measurement at a single time point may not reflect the long term outcome of
      ACL reconstruction surgery. The changes were however small and may not be
      clinically relevant. However, the consistently reduced external knee adduction
      moment seen about the reconstructed knee in this study may suggest that factors
      other than joint moments influence degenerative change over time.

PMID- 22469774
TI  - Population genetic data for 10 X-STR loci in autochthonous Basques from Navarre
      (Spain).
AB  - Ten X chromosome markers (DXS6789, DXS6809, DXS7132, DXS7133, DXS7423, DXS8378,
      DXS9898, DXS9902, GATA172D05, and GATA31E08) were analyzed in a sample of 185
      unrelated autochthonous Basques from Navarre. Deviations from Hardy-Weinberg
      equilibrium and linkage disequilibrium between markers were not observed at any
      loci. Combined power of discrimination was 0.999999999 (females) and 0.999998764
      (males). Mean exclusion chance was 0.99999463 (trios) and 0.999761591 (duos).
      Pairwise genetic distances (Fst) of X-STR frequencies indicate significant
      differences in the allele frequency distribution between the autochthonous
      Basques from Navarre and American and Iberian populations except with the Basque
      Country.

PMID- 22469775
TI  - Hydration and temperature interdependence of protein picosecond dynamics.
AB  - We investigate the nature of the solvent motions giving rise to the rapid
      temperature dependence of protein picoseconds motions at 220 K, often referred to
      as the protein dynamical transition. The interdependence of picoseconds dynamics
      on hydration and temperature is examined using terahertz time domain spectroscopy
      to measure the complex permittivity in the 0.2-2.0 THz range for myoglobin. Both
      the real and imaginary parts of the permittivity over the frequency range
      measured have a strong temperature dependence at >0.27 h (g water per g protein),
      however the permittivity change is strongest for frequencies <1 THz. The
      temperature dependence of the real part of the permittivity is not consistent
      with the relaxational response of the bound water, and may reflect the low
      frequency protein structural vibrations slaved to the solvent excitations. The
      hydration necessary to observe the dynamical transition is found to be frequency
      dependent, with a critical hydration of 0.19 h for frequencies >1 THz, and 0.27 h
      for frequencies <1 THz. The data are consistent with the dynamical transition
      solvent fluctuations requiring only clusters of ~5 water molecules, whereas the
      enhancement of lowest frequency motions requires a fully spanning water network.

PMID- 22469776
TI  - Novel estradiol based metal complexes of Tc-99m.
AB  - Aiming to contribute to the design of technetium imaging agents for estrogen
      receptor (ER) positive breast tumors, we have synthesized and evaluated the novel
      organometallic estradiol complexes (fac-[M(CO)(3)(kappa(3)-10)](+) and fac
      [M(CO)(3)(kappa(3)-12) M=Re/(99m)Tc) using two different bifunctional tridentate
      ligands (4 and 8). The rhenium complexes (13 and 14) were fully characterized by
      IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analyses. The (99m)Tc
      complexes (15 and 16) were obtained with high radiochemical purity and exhibited
      high in vitro radiochemical stability. To get a first insight into the relevance
      of these complexes for targeting ER positive tumors, ER binding affinity assays
      and cellular internalization studies in an ER expressing cell line, MCF-7, have
      also been performed suggesting a non ER mediated uptake.

PMID- 22469777
TI  - Structure of iron phosphate glasses modified by alkali and alkaline earth
      additions: neutron and x-ray diffraction studies.
AB  - The structure of iron phosphate glasses modified by additions of K(2)O and BaO,
      with nominal molar compositions [(1 - x)(0.6P(2)O(5)-0.4Fe(2)O(3))]xMe(y)O, where
      x = 0-0.4 in increments of 0.1; Me=K or Ba; and y = 1 or 2, has been investigated
      using neutron diffraction and x-ray diffraction techniques. Fitted coordination
      numbers for P-O and Fe-O showed a notable change in the P-O(NBO) and P-O(BO)
      contributions at greater than 20 mol% modifier addition, with barium producing a
      markedly larger increase in P-O(NBO) contribution than potassium. Fitting of
      T(N)(r) and T(X)(r) provided average n(BaO) = 9 and n(KO) = 6. Iron occurs in a
      range of coordination sites in these glasses: ([6])Fe(2+), ([4])Fe(3+),
      ([5])Fe(3+) and ([6])Fe(3+). The partitioning between these sites gives average
      n(FeO) = 5.2-5.8, with barium-doped glasses exhibiting higher average n(FeO) than
      potassium-doped glasses. The stronger depolymerizing effect of Ba(2+) than K(+)
      on the phosphate network, coupled with its greater ionic charge and higher Me-O,
      Fe-O and O...O coordination numbers, explain previously observed divergences in
      physical properties between the barium-doped and the potassium-doped glasses.

PMID- 22469778
TI  - Accounting for nature's benefits: the dollar value of ecosystem services.

PMID- 22469779
TI  - The spatial impact of visual distractors on saccade latency.
AB  - Remote transient changes in the environment, such as the onset of visual
      distractors, impact on the execution of target directed saccadic eye movements.
      Studies that have examined the latency of the saccade response have shown
      conflicting results. When there was an element of target selection, saccade
      latency increased as the distance between distractor and target increased. In
      contrast, when target selection is minimized by restricting the target to appear
      on one axis position, latency has been found to be slowest when the distractor is
      shown at fixation and reduces as it moves away from this position, rather than
      from the target. Here we report four experiments examining saccade latency as
      target and distractor positions are varied. We find support for both a dependence
      of saccade latency on distractor distance from target and from fixation: saccade
      latency was longer when distractor is shown close to fixation and even longer
      still when shown in an opposite location (180 degrees ) to the target. We suggest
      that this is due to inhibitory interactions between the distractor, fixation and
      the target interfering with fixation disengagement and target selection.

PMID- 22469780
TI  - B-cell regulator of immunoglobulin heavy-chain transcription (Bright)/ARID3a is a
      direct target of the oncomir microRNA-125b in progenitor B-cells.
AB  - B-cell acute lymphoblastic leukemia (B-ALL) is often associated with chromosomal
      translocations leading to the deregulation of proto-oncogenes. MicroRNAs can also
      be affected by chromosomal alterations and thus contribute to carcinogenesis. The
      microRNA, miR-125b-1, is overexpressed in B-ALL cases with the t(11;14)(q24;q32)
      translocation; therefore, we sought to determine the role of this microRNA in B
      cell fate. We used murine pre-BI cells alongside murine and human leukemic B-cell
      lines to show that miR-125b expression enhances proliferation by targeting B-cell
      regulator of immunoglobulin heavy-chain transcription (Bright)/ARID3a, an
      activator of immunoglobulin heavy-chain transcription. Accordingly, this target
      gene was downregulated in B-ALL patients with the t(11;14)(q24;q32)
      translocation. Repression of Bright/ARID3a blocked differentiation and conferred
      a survival advantage to Ba/F3 cells under interleukin-3 starvation. In addition,
      overexpression of miR-125b protected pre-BI and leukemic B-cell lines from
      apoptosis by blockade of caspase activation by a mechanism that was independent
      of p53 and BAK1. In summary, miR-125b can act as an oncogene in B-ALL by
      targeting ARID3a and mediating its repression, thus leading to a blockage in
      differentiation, increased proliferation and inhibition of apoptosis.

PMID- 22469782
TI  - TET2 is essential for survival and hematopoietic stem cell homeostasis.
AB  - Ten-Eleven-Translocation 2 (TET2) is an enzyme that catalyzes the conversion of 5
      methylcytosine into 5-hydroxymethylcytosine (5-hmC) and thereby alters the
      epigenetic state of DNA; somatic loss-of-function mutations of TET2 are
      frequently observed in patients with diverse myeloid malignancies. To study the
      function of TET2 in vivo, we analyzed Ayu17-449 (TET2(trap)) mice, in which a
      gene trap insertion in intron 2 of TET2 reduces TET2 mRNA levels to about 20% of
      that found in wild-type (WT) mice. TET2(trap/trap) mice were born at Mendelian
      frequency but died at a high rate by postnatal day 3, indicating the essential
      role of TET2 for survival. Loss of TET2 results in an increase in the number of
      hematopoietic stem cells (HSCs)/progenitors in the fetal liver, and
      TET2(trap/trap) HSCs exhibit an increased self-renewal ability in vivo. In
      competitive transplantation assays, TET2(trap/trap) HSCs possess a competitive
      growth advantage over WT HSCs. These data indicate that TET2 has a critical role
      in survival and HSC homeostasis.

PMID- 22469781
TI  - Using combination therapy to override stromal-mediated chemoresistance in mutant
      FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted
      inhibitors and JAK inhibitors.
AB  - Acute myeloid leukemia (AML) progenitors are frequently characterized by
      activating mutations in the receptor tyrosine kinase Fms-like tyrosine kinase-3
      (FLT3). Protein tyrosine kinases are integral components of signaling cascades
      that have a role in both FLT3-mediated transformation as well as viability
      pathways that are advantageous to leukemic cell survival. The bone marrow
      microenvironment can diminish AML sensitivity to tyrosine kinase inhibitors. We
      hypothesized that inhibition of protein kinases in addition to FLT3 may be
      effective in overriding drug resistance in AML. We used a cell-based model
      mimicking stromal protection as part of an unbiased high-throughput chemical
      screen to identify kinase inhibitors with the potential to override
      microenvironment-mediated drug resistance in mutant FLT3-positive AML. Several
      related multi-targeted kinase inhibitors, including dasatinib, with the
      capability of reversing microenvironment-induced resistance to FLT3 inhibition
      were identified and validated. We validated synergy in vitro and demonstrated
      effective combination potential in vivo. In particular Janus kinase inhibitors
      were effective in overriding stromal protection and potentiating FLT3 inhibition
      in primary AML and cell lines. These results hint at a novel concept of using
      combination therapy to override drug resistance in mutant FLT3-positive AML in
      the bone marrow niche and suppress or eradicate residual disease.

PMID- 22469783
TI  - The N363S and I559N single nucleotide polymorphisms of the h-GR/NR3C1 gene in
      patients with bronchial asthma.
AB  - Bronchial asthma is a disease of multifactorial etiology. The natural variability
      of the DNA sequence within the h-GR/NR3C1 gene affects both the conformation and
      the activity of glucocorticoid receptors. There are 2 major types of resistance
      to glucocorticoids (GCS)-resistant asthma failing to respond to treatment with
      high doses of inhaled and oral glucocorticoids. Type I GCS-resistant asthma is
      cytokine-induced or acquired. Type II GCS resistance involves generalized primary
      cortisol resistance, which affects all tissues and is likely to be associated
      with a mutation in the glucocorticoid receptor (GCR) gene or in genes that
      modulate GCR function. There are clear examples of glucocorticoid gene h-GR/NR3C1
      polymorphisms that can influence responses and sensitivity to
      glucocorticosteroids. Among the numerous polymorphisms observed within this gene,
      N363S and I559N single nucleotide polymorphisms (SNPs) may play an important role
      in the development of bronchial asthma and in the alteration of sensitivity to
      GCS in severe bronchial asthma. The aim of this research project was to study the
      correlation between the N363S and I559N polymorphisms of the h-GR/NR3C1 gene and
      the occurrence of asthma in a population of Polish asthmatics. Peripheral blood
      was obtained from 210 healthy volunteers and 234 asthma patients. Structuralized
      anamnesis, spirometry and allergy skin prick tests were performed in all
      participants. Genotyping was carried out using the polymerase chain reaction
      (PCR)-restriction fragment length polymorphism (RFLP) and PCR-HRM methods. In the
      healthy, non-atopic population, the GG variant of the N363S polymorphism was
      found with a 5.7% frequency. In asthma patients, GG SNP of N363S occurred with
      the frequency of 6.4%. In the groups of patients with uncontrolled moderate
      asthma and uncontrolled severe disease, the genotype distribution for the
      investigated polymorphisms were as follows: N363S, AA, AG, GG occurring with
      0.8750/0.0834/0.0416 frequency and I559N, TT, TA, AA occurring with
      1.000/0.000/0.000 frequency. The analysis demonstrated a significantly higher
      frequency of the A and G variants of the N363S polymorphisms in uncontrolled
      moderate asthma and uncontrolled severe disease than in the healthy population.
      No variant-related differences in the frequency of the studied I559N polymorphism
      were demonstrated in healthy controls and asthma patients. In conclusion, the
      N363S polymorphism of the h-GR/NR3C1 gene is significantly associated with an
      increased sensitivity to glucococorticoids in vivo and susceptibility to the
      development of a moderate to severe form of uncontrolled bronchial asthma in the
      Polish population. This observation needs to be confirmed in a larger group of
      subjects.

PMID- 22469784
TI  - Berberine inhibits the proliferation of colon cancer cells by inactivating
      Wnt/beta-catenin signaling.
AB  - Colon cancer is one of the most common malignancies, mainly initiated by the
      abnormal activation of Wnt/beta-catenin signaling. In this study, we investigated
      the proliferation inhibitory effect of berberine on colon cancer cells and the
      molecular basis underlying this effect. With the viability, apoptosis and cell
      cycle assay, we demonstrated that berberine can inhibit proliferation, induce
      apoptosis and cell cycle arrest in colon cancer cells. In in vivo investigation,
      we demonstrated that berberine can prevent the colon cancer formation initiated
      by dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in rats. We employed
      western blotting, reverse transcription and polymerase chain reaction, special
      antagonist, overexpression and knockdown techniques to dissect the possible
      molecular mechanisms mediating the function of berberine. We found that the
      protein levels of beta-catenin in the nucleus and cytoplasm were all reduced
      after treating the colon cancer cells with berberine, and this may not result
      from accelerating the degradation of beta-catenin in the cytoplasm, but from
      inhibiting the mRNA expression of beta-catenin. Our results indicate that
      berberine can be a potential chemoprevention and chemotherapy agent for human
      colon cancer by targeting Wnt/beta-catenin signaling.

PMID- 22469785
TI  - Action of sisal (Agave sisalana, Perrine) extract in the in vitro development of
      sheep and goat gastrointestinal nematodes.
AB  - Active compounds from Agave sisalana with antiparasitic action against
      gastrointestinal nematodes (GINs) could be an alternative to diversify the range
      of parasite management methods in the livestock sector. The objective of this
      study was to evaluate the in vitro action of A. sisalana extract on the
      development of sheep and goat GINs. The extract, obtained from shredded sisal
      leaves, was utilized at various concentrations in the egg hatch test (EHT),
      larval development test (LDT), larval feeding inhibition test (LFIT) and adult
      motility test (AMT). The LC(50) and LC(95) in the EHT were 6.90 and 24.79 mg/mL,
      in the LDT were 0.041 and 0.067 mg/mL and in the LFIT were 0.053 and 0.24 mg/mL,
      respectively, showing a dose-dependent relationship. The development and feeding
      inhibition on L(1) were both 100% at a dose of 0.12 mg/mL. In the AMT there was
      100% inhibition at 75 mg/mL after 24h of exposure. The extract of A. sisalana
      therefore demonstrated significant action on L(1) at 0.12 mg/mL. So, if part of
      the A. sisalana extract passes through the animal's gastrointestinal system, this
      material can have a significant effect on the parasites in the feces. This is an
      interesting approach because it can drastically reduce the pasture contamination
      as well as the infection of herds.

PMID- 22469786
TI  - miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer
      cells by directly interacting with PRL-3.
AB  - The phosphatase of regenerating liver-3 (PRL-3) gene is associated with
      metastasis in gastric cancer, and is believed to play a causative role by
      promoting tumor cell motility, invasion, and metastasis, but little is known of
      the mechanisms involved. We previously reported that PRL-3 expression is
      significantly higher in the tissues of primary gastric carcinomas with peritoneal
      metastasis. In the present study, we found that two microRNAs (miRNAs), miR-495
      and miR-551a, predicted to target PRL-3, are downregulated in gastric carcinoma
      samples. The validation of this interaction between those two miRNAs and PRL-3
      was confirmed by western blotting and quantitative real-time PCR (qPCR) in GC
      cell lines transfected with miR-495 and miR-551a mimics. Furthermore, the
      migration and invasion of GC cells were significantly inhibited by transfection
      with miR-495 or -551a mimics, and the mRNA and protein levels of PRL-3 were
      reduced in cells overexpressing miR-495 or -551a. Collectively, our findings
      suggest that miR-495 and miR-551a both act as tumor suppressors by targeting the
      PRL-3 oncogene and inhibiting gastric cancer cell migration and invasion. The
      findings of this study contribute to current understanding of the functions of
      miRNA mimics in GC gene therapy.

PMID- 22469787
TI  - The effects of age and parity on anorectal function.

PMID- 22469788
TI  - Sacral nerve stimulation for constipation in children:  a caution for a treatment
      in development.

PMID- 22469789
TI  - Genetic risk profiling and gene signature modeling to predict risk of
      complications after IPAA.
AB  - BACKGROUND: Severe pouchitis and Crohn's disease-like complications are 2 adverse
      postoperative complications that confound the success of the IPAA in patients
      with ulcerative colitis. To date, approximately 83 single nucleotide
      polymorphisms within 55 genes have been associated with IBD. OBJECTIVE: The aim
      of this study was to identify single-nucleotide polymorphisms that correlate with
      complications after IPAA that could be utilized in a gene signature fashion to
      predict postoperative complications and aid in preoperative surgical decision
      making. DESIGN: One hundred forty-two IPAA patients were retrospectively
      classified as "asymptomatic" (n = 104, defined as no Crohn's disease-like
      complications or severe pouchitis for at least 2 years after IPAA) and compared
      with a "severe pouchitis" group (n = 12, >= 4 episodes pouchitis per year for 2
      years including the need for long-term therapy to maintain remission) and a
      "Crohn's disease-like" group (n = 26, presence of fistulae, pouch inlet
      stricture, proximal small-bowel disease, or pouch granulomata, occurring at least
      6 months after surgery). Genotyping for 83 single-nucleotide polymorphisms
      previously associated with Crohn's disease and/or ulcerative colitis was
      performed on a customized Illumina genotyping platform. The top 2 single
      nucleotide polymorphisms statistically identified as being independently
      associated with each of Crohn's disease-like and severe pouchitis were used in a
      multivariate logistic regression model. These single-nucleotide polymorphisms
      were then used to create probability equations to predict overall chance of a
      positive or negative outcome for that complication. RESULTS: The top 2 single
      nucleotide polymorphisms for Crohn's disease-like complications were in the 10q21
      locus and the gene for PTGER4 (p = 0.006 and 0.007), whereas for severe pouchitis
      it was NOD2 and TNFSF15 (p = 0.003 and 0.011). Probability equations suggested
      that the risk of these 2 complications greatly increased with increasing number
      of risk alleles, going as high as 92% for severe pouchitis and 65% for Crohn's
      disease-like complications. CONCLUSION: In this IPAA patient cohort, mutations in
      the 10q21 locus and the PTGER4 gene were associated with Crohn's disease-like
      complications, whereas mutations in NOD2 and TNFSF15 correlated with severe
      pouchitis. Preoperative genetic analysis and use of such gene signatures hold
      promise for improved preoperative surgical patient selection to minimize these
      IPAA complications.

PMID- 22469790
TI  - Is an elective diverting colostomy warranted in patients with an endoscopically
      obstructing rectal cancer before neoadjuvant chemotherapy?
AB  - BACKGROUND: Many surgeons prefer immediate diversion in patients with
      endoscopically obstructed rectal cancer before starting neoadjuvant chemotherapy.
      OBJECTIVE: The aim of this study was to compare immediate neoadjuvant
      chemoradiotherapy with diversion for endoscopically obstructed rectal cancer.
      DESIGN: This study is a retrospective review of patients with rectal
      adenocarcinoma treated from January 2000 to December 2009. Demographic, tumor,
      treatment, and outcome data were obtained. Data were analyzed by the use of the
      Fisher exact probability test and the Student t test. SETTINGS: This study was
      conducted at a tertiary care hospital/referral center. PATIENTS: Included were
      patients with a rectal adenocarcinoma unable to be traversed endoscopically but
      without clinical evidence of obstruction before the initiation of neoadjuvant
      chemoradiotherapy. Patients with recurrent tumors or those who did not complete
      neoadjuvant chemoradiotherapy because of compliance were excluded. MAIN OUTCOME
      MEASURES: The primary outcomes measured were the interval from diagnosis to
      neoadjuvant chemoradiotherapy initiation and resection and the incidence of
      complete obstruction. RESULTS: Eighty-five patients with endoscopically
      obstructed rectal cancer were identified; 16 underwent immediate diversion before
      neoadjuvant chemoradiotherapy (diverted group) and 69 were treated with immediate
      neoadjuvant chemoradiotherapy. Five patients undergoing immediate neoadjuvant
      chemoradiotherapy presented with bloating and distension; 2 were treated with
      dietary modification, and 3 (4.3%) progressed to complete obstruction following
      completion of neoadjuvant chemoradiotherapy and required diversion. Both groups
      were similar in age, tumor height, and surgical margin status. Patients
      undergoing diversion required a significantly greater number of permanent stomas
      and were associated with a higher rate of radical pelvic surgery. There was a
      significant delay in the initiation of neoadjuvant chemoradiotherapy (p < 0.05)
      and proctectomy (p < 0.001) from the time of diagnosis in the diverted group
      compared with the immediate neoadjuvant chemoradiotherapy group. The tumors of
      patients undergoing diversions were more likely to be unresectable following
      neoadjuvant chemoradiotherapy. LIMITATIONS: This study was limited by its
      retrospective design and possible selection bias. CONCLUSIONS: Immediate
      diversion is unnecessary in endoscopically obstructed rectal cancer without
      clinical signs of obstruction. There appears to be a relationship between
      immediate diversion and delay in initiation of neoadjuvant chemoradiotherapy and
      proctectomy. We conclude that immediate neoadjuvant chemoradiotherapy in patients
      with endoscopically obstructed rectal cancer is safe and feasible.

PMID- 22469791
TI  - Overlapping sphincter repair:  does age matter?
AB  - BACKGROUND: The predictors of the outcomes following anal sphincteroplasty have
      not been well documented. OBJECTIVE: The aim was to evaluate age as a predictor
      of functional outcome and quality of life after overlapping sphincter repair.
      DESIGN: This study is a retrospective review of chart review followed by a
      prospective evaluation by the use of validated questionnaires. SETTINGS: Patients
      were assigned to group A (<= 60 years old) or group B (>60 years). PATIENTS:
      Included were patients with obstetric sphincter injuries who underwent
      overlapping sphincteroplasty between 1996 and 2007. MAIN OUTCOME MEASURES: The
      Fecal Incontinence Quality of Life Scale, Fecal Incontinence Severity Index, the
      Cleveland Global Quality of Life scale, and a patient satisfaction questionnaire
      were used to assess outcome. RESULTS: Three hundred twenty-one women underwent
      sphincteroplasty and 197 responded to this study, 146 (74.1%) patients in group A
      and 51 (25.9%) patients in group B. Median follow-up was 7.7 years (range, 4.7
      10.0). The mean overall Fecal Incontinence Quality of Life Scale was 11.0 +/-
      3.5. Median Fecal Incontinence Severity Index score was 29.8 +/- 15.9. Mean
      Cleveland Global Quality of Life scale was 0.7 +/- 0.2. The 2 groups were
      comparable for BMI (p = 1.0), ethnic background (p = 0.8), smoking (p = 0.8), and
      follow-up duration (p = 0.9). Intergroup comparison showed no significant
      difference in the Fecal Incontinence Quality of Life Scale scores (p = 0.5) in
      all subscales: lifestyle (p = 0.8), coping behavior (p = 0.5), depression and
      self-perception (p = 0.2), and embarrassment (p = 0.1). No significant
      differences were noted in Fecal Incontinence Severity Index (p = 0.2), Cleveland
      Global Quality of Life scale (p =1.0), or postoperative satisfaction (p = 0.6).
      LIMITATIONS: The study was limited by its retrospective nature. CONCLUSIONS:
      Comparable long-term Fecal Incontinence Severity Index score and Fecal
      Incontinence Quality of Life Scale scores following overlapping sphincter repair
      suggest that age is not a predictor of outcome for overlapping sphincter repair.
      This procedure can be offered to both young and older patients.

PMID- 22469792
TI  - Management and outcome of local recurrence following transanal endoscopic
      microsurgery for rectal cancer.
AB  - BACKGROUND: Transanal endoscopic microsurgery is a faster and safer alternative
      to traditional surgical treatment of adenomas and low-risk (T1) rectal tumors.
      However, although overall survival appears similar, transanal endoscopic
      microsurgery has been shown to have higher recurrence rates. OBJECTIVE: The aim
      of this study was to investigate the management of patients with local recurrence
      after transanal endoscopic microsurgery and to evaluate their long-term outcome.
      DESIGN: This study was a retrospective review of medical records. SETTING:
      Patients were treated at a large tertiary-care hospital in Rome, Italy, between
      1990 and 2011. PATIENTS: Of 298 patients who underwent local excision with
      transanal endoscopic microsurgery, 144 patients with rectal adenocarcinoma were
      included in the study. INTERVENTION: Local excision was performed with transanal
      endoscopic microsurgery. In all cases complete full-thickness excision was
      attempted. MAIN OUTCOME MEASURES: Patient characteristics, operative record,
      pathology report, and tumor recurrence were analyzed. Survival was calculated
      using the Kaplan-Meyer method and groups were compared with the log-rank test.
      RESULTS: Tumors were classified as pT1 in 86 patients (59.7%), pT2 in 38 (26.4%),
      and pT3 in 20 (13.9%). Median follow-up was 85 (range, 3-234) months. Median time
      to recurrence was 11.5 (range, 1-62) months; 44 patients had local or distal
      recurrence or both. The rate of local recurrence for patients with pT1 tumors was
      11.6% (10/86). A total of 27 patients (18.8%) with local recurrence were eligible
      for salvage surgery: 17 had radical salvage resection, 9 had transanal re
      excision, and 1 refused surgery. Overall 5-year survival was 83% in all 144
      patients, and 92% in patients with pT1 tumors. The overall 5-year survival rate
      was higher in patients who had the radical salvage procedure than in those who
      had transanal re-excision (69% vs 43%; p = 0.05). LIMITATIONS: The study was
      limited by its retrospective nature, lack of technology at the beginning of the
      study, and the mixed nature of the study group. CONCLUSIONS: The outcome after
      transanal excision for rectal cancer depends on close surveillance for early
      detection of recurrence. In patients able to undergo surgery, endoluminal or
      pelvic recurrence should be treated with an immediate radical salvage operation.
      Overall long-term survival after local excision with transanal endoscopic
      microsurgery followed by radical salvage surgery in cases of local recurrence is
      comparable to overall survival after initial radical surgery.

PMID- 22469793
TI  - Outcomes from IBD-associated and non-IBD-associated colorectal cancer: a
      Surveillance Epidemiology and End Results Medicare study.
AB  - BACKGROUND: There is controversy as to whether the clinicopathological features
      of colorectal cancer in the setting of IBD are distinct from sporadic colorectal
      cancer. OBJECTIVE: The aim of this study was to compare the characteristics and
      outcomes between IBD-associated and sporadic colorectal cancer. DESIGN: This
      retrospective population-based cohort study used the Surveillance, Epidemiology,
      and End Results Medicare-linked database. SETTINGS: This study was conducted in 6
      US metropolitan areas enrolled in Surveillance, Epidemiology, and End Results.
      PATIENTS: Beneficiaries of Medicare parts A and B identified from the
      Surveillance, Epidemiology, and End Results database with a diagnosis of IBD
      associated or sporadic colorectal cancer who underwent surgical resection were
      included in the study. MAIN OUTCOMES MEASURES: The main outcome was death. The
      adjusted risk ratio for death compared patients with IBD-associated colorectal
      cancer with patients who had sporadic colorectal cancer. RESULTS: Patients with
      IBD-associated colorectal cancer were more likely to present at an earlier stage,
      use immunosuppression, and have metachronous colorectal cancer. Although total
      proctocolectomy was more common among IBD patients with colorectal cancer, the
      majority (>75%) underwent a segmental resection. Cancer-specific survival was
      worse for IBD-associated colorectal cancer vs sporadic colorectal cancer (mean,
      32.9 months vs 42.4 months). After adjusting for potential confounders, older
      age, male sex, higher stage, IBD, immunosuppression, neoadjuvant radiation, and
      metachronous tumor were associated with a higher risk of cancer-specific
      mortality. Among patients with IBD, there was no difference in cancer-specific
      survival for segmental colectomy vs proctocolectomy. LIMITATIONS: This is a
      retrospective cohort study utilizing insurance data dependent on the correct
      coding of patient claims. CONCLUSION: Older patients with IBD-associated
      colorectal cancer appear to have a slightly worse outcome than those with
      sporadic colorectal cancer. The cause of this is multifactorial, but it does not
      appear to be associated with a more limited surgical resection.

PMID- 22469794
TI  - Sacral neuromodulation therapy:  a promising treatment for adolescents with
      refractory functional constipation.
AB  - BACKGROUND: Sacral neuromodulation therapy has been successfully applied in adult
      patients with urinary and fecal incontinence and in adults with constipation not
      responding to intensive conservative treatment. No data, however, are available
      on sacral neuromodulation therapy as a treatment option in adolescents with
      refractory functional constipation. OBJECTIVES: This study aimed to describe the
      short-term results of sacral neuromodulation in adolescents with chronic
      functional constipation refractory to intensive conservative treatment. DESIGN:
      This is a retrospective review. SETTING: This study took place at the Department
      of Surgery, Maastricht University Medical Centre, The Netherlands. PATIENTS:
      Thirteen patients (all girls, age 10-18 years) with functional constipation
      according to the ROME III criteria not responding to intensive oral and rectal
      laxative treatment were assigned for sacral neuromodulation. MAIN OUTCOME
      MEASURES: When improvement of symptoms was observed during the testing phase, a
      permanent stimulator was implanted. Patients were prospectively followed up to at
      least 6 months after implantation of the permanent stimulator by interviews,
      bowel diaries, and Cleveland Clinic constipation score. Improvement was defined
      as spontaneous defecation >= 2 times a week. RESULTS: At presentation, none of
      the patients had spontaneous defecation or felt the urge to defecate. All
      patients had severe abdominal pain. Regular school absenteeism was present in 10
      patients. After the testing phase, all but 2 patients had spontaneous defecation
      >= 2 times a week with a reduction in abdominal pain. After implantation, 11 (of
      12) had a normal spontaneous defecation pattern of >= 2 times a week without
      medication, felt the urge to defecate, and perceived less abdominal pain without
      relapse of symptoms until 6 months after implantation. The average Cleveland
      Clinic constipation score decreased from 20.9 to 8.4. One lead revision and 2
      pacemaker relocations were necessary. LIMITATIONS: This study is limited by its
      small sample size, single-institution bias, and retrospective nature. CONCLUSION:
      Sacral neuromodulation appears to be a promising new treatment option in
      adolescents with refractory functional constipation not responding to intensive
      conservative therapy. Larger randomized studies with long-term follow-up are
      required.

PMID- 22469795
TI  - The effects of age and childbirth on anal sphincter function and morphology in
      999 symptomatic female patients with colorectal dysfunction.
AB  - BACKGROUND AND OBJECTIVES: Conflicting data exist on the contributions of
      advancing age and childbirth on the structure and function of the anal sphincter.
      This study aimed to examine the relative contributions of age and childbirth in a
      large cohort of women referred for investigation of symptoms of colorectal
      dysfunction (fecal incontinence and constipation). SETTING: This study was
      conducted at a specialist surgical colorectal investigation unit in a university
      teaching hospital. PATIENTS: Retrospective analysis was performed on
      prospectively collected demographic, symptom profile, and physiologic data from
      3686 female patients. Strict exclusion criteria were applied, leaving 999
      patients for univariate, multivariate, and logistic statistical modeling. MAIN
      OUTCOME MEASURES: The effects of independent variables alone and in combination
      on anal sphincter pressures (resting and squeeze increment) and the presence of
      sphincter defects (internal and external) were expressed as regression
      coefficients and odds ratios. RESULTS: Median age was 42 years (range, 16-88),
      and parity was 2 (range, 0-11); 16% were nulliparous. Three hundred sixty
      patients had fecal incontinence, 352 had constipation, and 287 had combined
      symptoms. Anal resting tone decreased with age by 0.66 cm H2O per year, and by
      4.3 cm H2O per birth, and was associated with both internal and external anal
      sphincter defects (p = 0.0001 for both). Squeeze increment pressures decreased by
      0.3 cm H2O per year, and by 3.8 cm H2O per birth; decreased pressures were,
      however, only significantly associated with external anal sphincter defects (p =
      0.0001) as a result of childbirth. Cesarean delivery was protective against both
      reduced anal pressures and sphincter defects. Pudendal nerve terminal motor
      latencies increased bilaterally with age and with vaginal delivery; the impact of
      both was greater on the left nerve. Rectal sensation was unaffected by age or
      parity. CONCLUSIONS: Aging predominantly affects anal resting pressures;
      childbirth, particularly instrumental delivery, is detrimental to the structure
      and function of the external sphincter.

PMID- 22469796
TI  - Identification of consensus-based quality end points for colorectal surgery.
AB  - BACKGROUND: Process and outcome measures for quality assessment of colorectal
      surgical care are poorly defined. OBJECTIVE: The aim of this study was to develop
      candidate end points for use in surgeon-specific registries designed for case
      reporting and quality improvement program development. DESIGN: The study design
      was based on modified Delphi-based development of consensus quality end points.
      SETTING: This study was undertaken by the American Society of Colon and Rectal
      Surgeons Executive Council, Quality Committee, and by the ColoRectal Education
      System Template Committee, American Board of Colon and Rectal Surgery. PATIENTS:
      No patients were included in this study. INTERVENTIONS: Six areas of colorectal
      surgery were defined by members of the American Society of Colon and Rectal
      Surgeons' Executive Council and the American Board of Colon and Rectal Surgery to
      cover areas of importance for colorectal surgeons. These included colectomy,
      rectal cancer, hemorrhoidectomy, anal fistula and abscess, colonoscopy, and
      rectal prolapse. Relevant American Society of Colon and Rectal Surgeons'
      committee members through a series of 4 panel discussions identified important
      demographic, process, and outcome measures in each of these 6 areas that might be
      suitable for the American College of Surgeons case log. Panel size was
      sequentially expanded from 8 members to 28 members to include all active
      committee members. Panelists contributed additional process and outcome measures
      for inclusion during each discussion. Modified Delphi methodology was used to
      generate consensus, and, after each panel discussion, members rated the relative
      importance of each end point from 1 (least important) to 4 (most important). MAIN
      OUTCOME MEASURES: The mean rating for each process and outcome measure after each
      round was recorded with the use of standardized definitions for relevant
      variables. RESULTS: Eighty-nine process and outcome measures were compiled and
      rated. Mean scores following the final round ranged from a low of 1.3 (anal
      fistula/abscess, preoperative imaging) to a high of 4.0 (colectomy-anastomotic
      leak). LIMITATIONS: The limitations of this study involved the use of consensus,
      small study size, and the fact that no end points were excluded. CONCLUSIONS:
      With the use of modified Delphi methodology, a consensus-derived ranked list of
      89 process and outcome measures was developed in 6 key areas of colorectal
      surgery. These data provide a framework for development of guideline standards
      for case-reporting program development initiatives for colon and rectal surgery.

PMID- 22469797
TI  - Long-term outcomes of sacral nerve stimulation for fecal incontinence.
AB  - BACKGROUND AND OBJECTIVE: In patients with fecal incontinence who do not benefit
      from medical or behavioral treatments sacral nerve stimulation is now considered
      a first-line procedure. Although the efficacy of treatment appears to be
      sustained in the short and medium term, the long-term results of therapy are
      relatively unknown. OBJECTIVE: We report the results of chronic sacral nerve
      stimulation in patients who have had more than 8 years of therapy. DESIGN AND
      SETTINGS: All patients who underwent sacral nerve stimulation for fecal
      incontinence from 1996 to 2002 were followed up prospectively. Data were
      collected prospectively by the use of bowel habit diaries and St Mark's
      continence scores. Treatment success was defined as >50% reduction in episodes of
      fecal incontinence with sacral nerve stimulation in comparison with baseline
      symptoms. RESULTS: Between January 1996 and December 2002, 25 patients
      (male/female 2:23; median age, 54 years (range, 35-68 years) underwent temporary
      sacral nerve stimulation. Twenty-three (92%) patients had a greater than 50%
      improvement in their ability to defer defecation during the trial phase and were
      considered suitable for chronic stimulation. Over a median follow-up of 114
      months (range, 96-164 months), full continence was maintained in 12 (48%) of the
      23 patients who received a neurostimulator implant. Two patients lost efficacy at
      48 and 60 months after permanent implant for unknown reasons and had the device
      removed. Three patients died at 3, 8, and 9 years after permanent implant because
      of unrelated comorbidities. Nine patients required a change of battery at a mean
      (SD) of 87 (13.5) months. CONCLUSIONS: Sacral nerve stimulation can maintain a
      persistent clinical benefit in the long term for the majority of patients. Some
      patients will experience deterioration in their symptoms over time, for reasons
      yet unknown.

PMID- 22469798
TI  - Prognostic impact of lymph node harvest and lymph node ratio in patients with
      colon cancer.
AB  - BACKGROUND: The prognostic impact of the number of lymph nodes and ratio in colon
      cancer is still debated. OBJECTIVES: The aim of this study was to evaluate lymph
      node harvest in patients with colon cancer over time, and to test the hypotheses
      that investigation of more lymph nodes, and low lymph node ratio in stage III
      patients, has positive prognostic impact. DESIGN: This is a prospective,
      observational study. SETTINGS: This study was conducted in a single institution
      treating all patients with colon cancer in a defined catchment area. PATIENTS:
      All patients admitted in the period 1993 to 2009 (n = 1481) were included. MAIN
      OUTCOME MEASURES: The primary outcomes measured were the number of examined
      regional lymph nodes according to treatment period, 5-year overall survival and
      time to recurrence, and univariate (Kaplan-Meier) and multivariate (Cox
      regression) analyses of prognostic factors. RESULTS: Nine hundred fifty (65%)
      patients underwent curative resection. Median number of examined lymph nodes
      increased from 7 to 15 (p < 0.001), and the proportion of patients with stage III
      disease increased from 25% to 33% (p = 0.02) during the study period. In patients
      with stage I to III disease, time to recurrence (proportion of patients without
      recurrence or death of colon cancer) improved from 65% to 82% during the period
      (p < 0.001). An association between lymph node count (<8 compared with >= 12) and
      overall survival was found for patients with stage II disease (57% vs 71%, p =
      0.004). Hazard ratio for death within 5 years was 0.7 (p = 0.043) when 8 to 11
      nodes were examined and 0.6 (p = 0.001) when >= 12 nodes were examined (<8
      reference). In patients with stage III disease, increasing lymph node ratio was
      associated with reduced overall survival and time to recurrence in uni- and
      multivariate analyses. LIMITATIONS: This study was limited by the small number of
      patients in each stage. CONCLUSIONS: The number of examined lymph nodes increased
      in the study period. A stage migration was observed, and time to recurrence
      improved in patients with stage I to III disease. In patients with stage III
      disease, lymph node ratio was a stronger prognostic factor than the total number
      of lymph nodes examined.

PMID- 22469799
TI  - Evaluation of the impact of implementing the prone jackknife position for the
      perineal phase of abdominoperineal excision of the rectum.
AB  - BACKGROUND: Abdominoperineal excision of rectum has been associated with poor
      oncological specimens and high local recurrence rates in comparison with
      restorative surgery. The role of recent changes in operative position has yet to
      be evaluated. OBJECTIVES: This study aimed to determine whether a change in the
      perineal phase from the Lloyd-Davies position to the prone jackknife position
      might improve excision margins and oncological outcomes. METHODS: A single
      institution review of a prospectively maintained database comparing the quality
      of excision and oncological outcomes after abdominoperineal excision in
      conventional and prone position was performed. Consecutive abdominoperineal
      excisions performed for adenocarcinoma of the rectum between January 1999 and
      April 2008 were included. RESULTS: Abdominoperineal excision cases were assessed
      including 63 in the Lloyd-Davies position and 58 in the prone jackknife position.
      The 5-year local recurrence rate was 5% in the prone jackknife group in
      comparison with 23% in the Lloyd-Davies group (p = 0.03) by life table analysis.
      For local recurrence, the most significant and independent risk factors were a
      favorable effect of having the patient in the prone jackknife position for the
      perineal phase of abdominoperineal excision (HR 0.2; 95% CI 0.04-0.81) and,
      unfavorably, a positive circumferential resection margin (HR 7.1; 95% CI 2.4-20).
      Lymph node involvement (N2) was an independent risk factor for overall survival
      (HR 4.6; 95% CI 2.1-9.5) and relapse of disease (HR 4.0; 95% CI 0.7-9.4).
      LIMITATIONS: This study has some limitations because it is a retrospective review
      of a prospective database. CONCLUSION: These data suggest that the rate of local
      recurrence after abdominoperineal excision may be lowered by adaptation of the
      prone jackknife position.

PMID- 22469800
TI  - Ileal pouch adenomas and carcinomas after restorative proctocolectomy for
      familial adenomatous polyposis.
AB  - BACKGROUND: Restorative proctocolectomy and IPAA has become the treatment of
      choice in familial adenomatous polyposis. However, several cases of adenomas and
      carcinomas arising in the ileal pouch were reported. OBJECTIVE: The aim of this
      study was to evaluate the prevalence and natural history of ileal pouch adenomas
      and the development of carcinomas in patients with restorative proctocolectomy
      for familial adenomatous polyposis. DESIGN AND SETTING: We prospectively studied
      patients who underwent IPAA during the past 20 years at the surgical unit of the
      University of Florence in Italy. MAIN OUTCOME MEASURES: We investigated the
      extent of the risk and the factors that are involved in the development of
      neoplastic changes of the pouch. Furthermore, because it is not entirely clear
      when and how polyps should be treated, we have revised our modality of treatment
      for this unusual pathology. PATIENTS: Sixty-nine patients with familial
      adenomatous polyposis underwent restorative proctocolectomy. In 66 patients,
      handsewn ileoanal anastomosis with anal canal mucosectomy was performed. After
      surgery, all patients underwent endoscopic surveillance. RESULTS: After 10 years
      of follow-up, 1 ileal pouch adenoma was found in 64.9% of restorative
      proctocolectomy patients, and ileal pouch carcinomas occurred in 2 patients (29
      and 59 years old), 3 and 11 years after restorative proctocolectomy. The number
      of colonic adenomatous polyps influenced the occurrence of pouch adenomas. No
      patients with <200 colonic adenomas experienced pouch adenomas, but 46% of
      patients with >1000 colonic polyps had pouch adenomas, and 25% of patients with
      200 to 1000 colonic polyps had pouch adenomas at follow-up. No relationship was
      found between ileal pouch adenomas and pouch shape (J, S, or straight ileoanal
      anastomosis with multiple myotomies) or the APC mutation. Polyps larger than 5 mm
      were removed by endoscopy or surgery. CONCLUSIONS: Ileal pouch adenomas were
      common after restorative proctocolectomy. Patients >50 years of age and patients
      with >1000 colonic adenomas at the time of colectomy were more prone to ileal
      pouch adenomas. The development of malignancy in the terminal ileum can present a
      fast course and does not seem to follow the classic adenoma-carcinoma sequence.

PMID- 22469801
TI  - The long-term clinical course of pouchitis after total proctocolectomy and IPAA
      for ulcerative colitis.
AB  - BACKGROUND: Pouchitis is the most common long-term complication after restorative
      total proctocolectomy and IPAA for ulcerative colitis. OBJECTIVE: We examined the
      incidence, clinical aspects, and long-term outcome of patients with idiopathic
      pouchitis. DESIGN: This study was a retrospective review of medical records.
      PATIENTS: Included in the study were 284 patients with ulcerative colitis who
      underwent a total proctocolectomy and IPAA. MAIN OUTCOME MEASURES: We evaluated
      the cumulative risk and long-term outcome of pouchitis including the duration of
      disease, pattern of relapse, and responsiveness to antibiotic therapy. RESULTS:
      Sixty-four patients developed idiopathic pouchitis. The cumulative risk was 10.7%
      at 1 year, 17.2% at 2 years, 24.0% at 5 years, and 38.2% at 10 years. At their
      first pouchitis episode, 45 patients had acute pouchitis, 19 patients had chronic
      pouchitis, and all patients received antibiotic therapy with oral ciprofloxacin
      and/or metronidazole. The efficacy of the therapy was 96.6% initially. Forty-five
      patients had antibiotic-responsive pouchitis, 17 patients had antibiotic
      dependent pouchitis, and 2 patients had antibiotic-refractory pouchitis at their
      first episode. Whereas 20 of 45 patients (44.4%) with initially acute pouchitis
      experienced 2 or more relapses, 16 of 19 patients (84.2%) with initially chronic
      pouchitis had 2 or more relapses. After taking into account the relapses, the
      number of patients with antibiotic-responsive pouchitis decreased from 45 to 40,
      the number with antibiotic-dependent pouchitis increased from 17 to 20, and the
      number with antibiotic-refractory pouchitis increased from 2 to 4. Among the 4
      patients with antibiotic-refractory pouchitis, 3 patients had Clostridium
      difficile-associated pouchitis. LIMITATIONS: This study was retrospective.
      CONCLUSION: The patients with chronic pouchitis at the first episode tend to have
      a higher incidence of relapse. In some patients, the responsiveness to antibiotic
      therapy changes during follow-up. When patients with pouchitis do not respond to
      standard antibiotic therapy, then the occurrence of C difficile infection should
      be considered.

PMID- 22469802
TI  - Iron biomarkers in plasma, HFE genotypes, and the risk for colorectal cancer in a
      prospective setting.
AB  - BACKGROUND: High iron levels can increase the formation of noxious oxygen
      radicals, which are thought to promote carcinogenesis. OBJECTIVE: The aim of this
      prospective study was to determine whether iron biomarkers and HFE genotypes,
      which influence iron regulation, constitute risk factors for colorectal cancer.
      DESIGN: This is a prospective nested case-referent study. SETTINGS: The study was
      performed within the population-based Northern Sweden Health and Disease Study.
      PATIENTS: The study included 226 cases of colorectal cancer and 437 matched
      referents. MAIN OUTCOME MEASURES: Conditional regression analysis was performed.
      Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed.
      RESULTS: The highest quintile of total iron-binding capacity showed significantly
      higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38-4.02). When
      stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59
      7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5
      both in univariate and multivariate models. LIMITATIONS: Colorectal cancer may
      influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were
      too few to make conclusions for this group. The relatively short follow-up time
      might be insufficient to detect risk of iron biomarkers. CONCLUSIONS: High iron
      levels do not increase the risk of colorectal cancer. HFE genotypes influencing
      iron uptake had no effect on colorectal cancer risk.

PMID- 22469803
TI  - Intra-abdominal use of phosphodiesterase type 4 inhibitor in postoperative
      adhesion prevention: an experimental study on mice.
AB  - OBJECTIVE: The study was designed to assess the value of intraperitoneal use of
      rolipram for adhesion prevention and to compare the results with placebo and a
      sodium hyaluronate/carboxymethylcellulose absorbable barrier (Seprafilm), in a
      murine cecal abrasion model. DESIGNS: Twenty-four Balb/c mice were subjects of
      this study. Intra-abdominal adhesions were created with a multiple-abrasion model
      consisting of meticulous abrasion of the cecum and small-bowel segments with
      strokes of a dental toothbrush. Animals in groups R (n = 8) received 1 mL of
      rolipram intraperitoneally. Seprafilm was placed over the viscera under the
      incision in group S animals (n = 8). Group C animals (n = 8) were reserved as
      control and received nothing. Animals were killed on day 22. MAIN OUTCOME
      MEASURES: The adhesions were evaluated with 2 different observational scoring
      systems, the Majuzi System and the Linsky Scale. After completion of
      observational evaluation, the cecum and small bowel of the animals were excised
      and sent to the pathology laboratory for histopathologic examination. The extent
      of inflammatory response, the extent of the fibrotic reaction, the extent of the
      necrosis and abscess formation, and the extent of foreign body reaction were
      histologically evaluated. RESULTS: The mean Majuzi System scores of groups R and
      S were similar to each other and significantly less than control group. Also, all
      scores of the Linsky Scale in group R were similar to those in group S, and
      significantly less than those in the control group. Histologically, the mean
      score of inflammatory response in group R was less than both those in group C and
      group S. The mean score of fibrotic reaction in group R was significantly less
      than those in the control group. CONCLUSION: These results indicate that rolipram
      may be an effective material in prevention of postoperative intra-abdominal
      adhesions, but it is obvious that further studies are needed to validate the
      results of this limited initial study.

PMID- 22469804
TI  - A systematic review of the anal fistula plug for patients with Crohn's and non
      Crohn's related fistula-in-ano.
AB  - BACKGROUND: The management of fistula-in-ano is a balance between fistula cure
      and preservation of continence. OBJECTIVE: The aim of this study is to summarize
      the anal fistula plug literature for Crohn's and non-Crohn's fistula-in-ano in a
      homogenous patient population. DATA SOURCES: PubMed, MEDLINE, Embase, and
      Cochrane medical databases were searched from 1995 to 2011. Abstracts from The
      American Society of Colon and Rectal Surgeons, The Society for Surgery of the
      Alimentary Tract, The European Society of Coloproctology, and the Association of
      Coloproctology of Great Britain and Ireland meetings between 2007 and 2010 were
      also evaluated. STUDY SELECTION: Studies were included if results for patients
      with and without Crohn's disease could be differentiated. Patients with
      rectovaginal, anovaginal, rectourethral, or ileal-pouch vaginal fistulas were
      excluded as were studies where the mean or median follow-up was less than 3
      months. Two researchers independently selected studies matching the inclusion
      criteria. INTERVENTION: Anal fistula plug insertion was performed. MAIN OUTCOME
      MEASURES: The primary outcomes measured were the overall fistula closure rates
      and length of follow-up. RESULTS: Seventy-six articles or abstracts were
      identified from the title as being of relevance. Twenty studies (2 abstracts, 18
      articles) were finally included. Study sample size ranged from 4 to 60 patients;
      530 patients were included in all studies (488 non-Crohn's and 42 Crohn's
      patients). The plug extrusion rate was 8.7% (46 patients). The proportion of
      patients achieving fistula closure varied widely between studies for non-Crohn's,
      ranging from 0.2 (95% CI 0.04-0.48) to 0.86 (95% CI 0.64-0.97). The pooled
      proportion of patients achieving fistula closure in patients with non-Crohn's
      fistula-in-ano was 0.54 (95% CI 0.50-0.59). The proportion achieving closure in
      patients with Crohn's disease was similar (0.55, 95% CI 0.39-0.70). LIMITATIONS:
      This study was limited by the variability of operative technique and
      perioperative care between studies. CONCLUSIONS: Fistula closure is achieved by
      using the anal fistula plug in approximately 54% of patients without Crohn's
      disease. The anal fistula plug has not been adequately evaluated in the Crohn's
      population.

PMID- 22469805
TI  - Understanding MYH-associated neoplasia.

PMID- 22469806
TI  - Right colon to rectal anastomosis (Deloyers procedure) as a salvage technique for
      low colorectal or coloanal anastomosis: postoperative and long-term outcomes.
AB  - BACKGROUND: After extended left colectomy, it may be difficult to take down a
      well-vascularized colon into the pelvis and perform a tension-free colorectal or
      coloanal anastomosis. The Deloyers procedure comprising complete mobilization and
      rotation of the right colon while maintaining the ileocolic artery may be used in
      this circumstance. OBJECTIVE: The aim of this study is to report postoperative
      and long-term outcomes after the Deloyers procedure as a salvage technique for
      colorectal anastomosis or coloanal anastomosis. DESIGN: From a prospective
      database, we retrospectively reviewed all patients who underwent a Deloyers
      procedure. SETTING: This study was conducted at the Colorectal Unit in a tertiary
      referral teaching hospital. PATIENTS: Between 1998 and 2011, 48 consecutive
      patients underwent a Deloyers procedure. Indications were as following: Hartmann
      reversal (n = 17), previous colorectal anastomosis-related complications (n =
      11), diverticular disease (n = 6), left colon cancer (n = 6), ischemic colitis (n
      = 3), iterative colectomy for cancer (n = 3), rectal cancer local recurrence (n =
      1), and synchronous colon cancer (n = 1). RESULTS: There were 38 men and 10 women
      (median age at surgery, 67 years). Colorectal anastomosis and coloanal
      anastomosis were performed in 38 and 10 patients. Thirty-one patients had
      defunctioning stoma. Mortality and early morbidity rate was 2% and 23%. Three
      patients (6%) had severe complications (Dindo >= 3). There was no anastomotic
      leakage. Reoperation was required in 2 patients for intra-abdominal hemorrhage.
      The median hospital stay was 12 days. The median follow-up was 26 months. All
      patients had their ileostomy closed. Twenty-three percent of patients developed
      late complications. The median number of bowel movements per day was 3 (range, 1
      7), but 67% of patients had fewer than 3. One patient required an ileostomy
      refashioning because of poor functional results, and 23% of patients routinely
      take loperamide-based medication. LIMITATION: The retrospective nature of the
      study was a limitation. CONCLUSIONS: The Deloyers procedure is safe, associated
      with low morbidity and good long-term functional results. It represents a safe
      alternative to total colectomy and ileorectal anastomosis.

PMID- 22469807
TI  - Timing of surgery following preoperative therapy in rectal cancer:  there is no
      need for a prospective randomized trial.

PMID- 22469811
TI  - The limitations of partial citizenship: health care institutions underpinned with
      heteronormative ideals.
AB  - Tensions between apparent rights of lesbian, gay, bisexual, transgender, or
      queer/questioning people and the continued prevalence of heteronormative health
      care practice emerged in research with older women who self-identified as
      lesbian. Having already faced considerable exclusionary institutional practices
      in their lives, these women expressed anticipatory dread of the erasure of their
      lives in residential or long-term care. Drawing on the framework of sexual
      citizenship, this article critiques the disjuncture between the legal reality and
      the lived reality of LGBTQ people and suggests that social or political rights of
      full citizenship remain tenuous or absent in residential care settings. Authors
      present an alternative approach to human health experience.

PMID- 22469812
TI  - Time to disable the labels that disable: the power of words in nursing and health
      care with women, children, and families.
AB  - Nursing is grounded in communication with others, yet rarely are the words
      critiqued. Despite an ethical call to honor diversity, promote empowerment, and
      to do no harm, some of the language used in health care reflects historical
      prejudices, reductionism, and/or the overarching authority of medical or moral
      models. This article exposes some of the "harsh words" nurses sometimes
      unconsciously use, and it suggests alternatives. Influenced by an ethic of social
      justice and the ethic of relationship with others, an attempt will be made to
      explore nursing language with women and children. Implications for nursing
      philosophy and practice will be discussed.

PMID- 22469813
TI  - RNA interference targeting CHFR enhances taxol chemosensitivity in endometrial
      cancer cells.
AB  - In recent years, it has been reported that CHFR may be a useful biomarker for
      chemotherapeutic response to microtubule inhibitors in some tumor cells. The
      purpose of the present study was to test the hypothesis and to elucidate the
      underlying mechanism in endometrial cancer cells. First, we effectively inhibited
      CHFR expression at both the mRNA and protein levels using siRNA targeting the
      CHFR gene in Ishikawa and Hec-1a cells. We found that inhibition of CHFR
      expression significantly enhanced the cytotoxicity of taxol to both cell types,
      which was confirmed again by colony formation assays. Moreover, suppression of
      CHFR induced a significant increase of the mitotic index and much lower numbers
      of cells at the G2/M phase in both cells treated with taxol, indicating mitotic
      checkpoint impairment. On the other hand, the number of apoptotic cells
      significantly increased in Ishikawa and Hec-1a cells transfected with CHFR siRNA
      after treatment with taxol, which was associated with cyclin B1 nuclear
      localization. Our data indicate that RNA interference targeting CHFR can
      sensitize endometrial cancer cells to taxol and CHFR may be a promising molecular
      target to enhance the therapeutic effect of taxol for endometrial cancer.

PMID- 22469814
TI  - Short-term practice effects and variability in cognitive testing in a healthy
      elderly population.
AB  - BACKGROUND: Cognitive decline in the elderly is a subject of intense focus.
      However, there is a lack of consensus regarding definition of significant decline
      in connection with repeated testing and the interpretation of cognitive tests
      results must take into account the practice effect and variability in test
      performance. The aim of this study was to collect cognitive test results with
      repeated testing in an elderly healthy population. METHODS: 161 healthy controls
      >=60 years were included. Cognitive testing was performed upon entry into the
      study, at 1 week and 3 months. Practice effect was evaluated on 7
      neuropsychological measures and reference values of clinically important changes
      were calculated according to z-scores above 1.96. RESULTS: Test scores improved
      significantly (p<0.05) in 2 of 7 measures between baseline and 2nd test and in 6
      of 7 measures between baseline and 3rd test session. No significant correlation
      was found between magnitude of practice effect and age or educational status.
      CONCLUSION: Practice effect and variability in cognitive testing in the elderly
      are important to consider when evaluating changes in cognitive performance over a
      short period of time.

PMID- 22469815
TI  - Modelling of surface nanoparticle inclusions for nanomechanical measurements by
      an AFM or nanoindenter: spatial issues.
AB  - Finite element analysis (FEA) is used to model nanoindentation by a rigid,
      spherically shaped indenter, axially indenting an elastic two phase polymer
      system comprised of a cylindrical nanoparticle of compliant polymer set in a semi
      infinite matrix of stiffer polymer. The cylindrical nanoparticle is normal to the
      sample surface. An axisymmetric finite element model is used to determine the
      reduced modulus measured as a function of the indentation depth for various
      nanoparticle radii and extensions below the surface. We show how the previous
      simple analytical equations may be extended to describe these situations with
      accuracy. This gives excellent agreement with the FEA and provides a clear guide
      to the maximum indentation depth as a function of both the nanoparticle radius
      and its thickness consistent with a choice of either computation from the
      analytical equations or direct measurement with a maximum of 10% error in the
      measured reduced modulus.

PMID- 22469816
TI  - Perceived duration of plaid motion increases with pattern speed rather than
      component speed.
AB  - Several studies have shown that visual motion distorts perceived duration: The
      duration of fast-moving stimuli is judged to be longer than the same duration of
      stationary or slow-moving stimuli. However, it is still unclear which stages of
      motion processing are involved in this apparent dilation of the perceived
      duration. In this study, using a two-dimensional pattern motion of a plaid as a
      stimulus, we systematically manipulated the speed of pattern and component
      motions of the plaid to examine which motion information influences the perceived
      duration of the plaid stimuli. Experiment 1 found that perceived duration
      increased with pattern speed, even though component speed was constant.
      Experiments 2 and 3 revealed that perceived duration was unchanged, even though
      component speed increased, as long as the pattern speed was identical. Experiment
      4 used both static and moving plaids and confirmed that the results of
      Experiments 1-3 reflected duration dilation, not duration compression, induced by
      motion. These results suggest that higher order visual processing in the middle
      temporal area may play an important role in motion-induced duration dilation.

PMID- 22469817
TI  - Effects of Panax notoginseng flower extract on the TGF-beta/Smad signal
      transduction pathway in heart remodeling of human chymase transgenic mice.
AB  - Panax notoginseng is a common Chinese herb extensively used in Chinese medical
      practice for the treatment of cardiovascular diseases. The present study aimed to
      evaluate the effects of Panax notoginseng flower extract (PNFE) on the TGF
      beta/Smad signal transduction pathway in heart remodeling of human chymase
      transgenic mice. After treatment with PNFE and soybean trypsin inhibitor (SBTI),
      the left ventricular mass indexes (LVMIs) of transgenic and normal C57 BL/6 mice
      were analyzed. The mRNA expression of chymase, TGF-beta1, Smad2, Smad3 and Smad7
      in myocardium was assessed with RT-PCR, while the protein expression in
      myocardium was detected by western blotting. The results showed that PNFE and
      SBTI treatment led to a significant reduction in LVMIs in transgenic mice,
      indicating a beneficial effect on left ventricular remodeling. Mechanistically,
      PNFE and SBTI treatment attenuated the mRNA expression of chymase, TGF-beta1,
      Smad2 and Smad3, as well as the protein expression in the myocardium tissues of
      the transgenic mouse model. By contrast, PNFE and SBTI treatment markedly up
      regulated the mRNA and protein expression of Smad7. It was concluded that PNFE
      was able to improve the ventricular hypertrophy state in human chymase transgenic
      mice through regulation of the expression of mRNA and protein of TGF-beta/Smad in
      ventricular tissues.

PMID- 22469818
TI  - Detection of Chikungunya virus in Aedes aegypti during 2011 outbreak in Al
      Hodayda, Yemen.
AB  - In October 2010, the Ministry of Public Health and Population reported an
      outbreak of dengue-like acute febrile illness in Al Hodayda governorate. By
      January 2011, a total of 1542 cases had been recorded from 19 of the 26 districts
      in the governorate with 104 purportedly associated deaths. In response this
      event, in January 2011 entomological investigations aimed at identifying the
      primary vector and the epidemic associated etiological agent were carried out.
      Based on the reported cases and the progress of the outbreak in the governorate,
      mosquito collection was undertaken in two of the most recent outbreak areas; Al
      Khokha district (130km south of Al Hodayda) and Al Muneera district (100km
      north). Mosquito adults were collected from houses using BG-sentinelTM traps,
      aspiration of resting mosquitoes and knock-down spraying. Indoor and outdoor
      containers adjacent to the houses were inspected for larvae. Subsequently
      mosquito pools were analyzed by RT-PCR for detection of the four dengue virus
      serotypes (DENV-1, DENV-2, DENV-3, DENV-4), and for Chikungunya virus (CHIKV).
      Aedes aegypti was the dominant mosquito species collected. Four pools represent
      40% of the tested pools, all containing adult female Ae. aegypti, were positive
      for CHIKV. Three CHIKV isolates were obtained from the RNA positive mosquito
      pools and identified by rRT-PCR. This finding marks the first record of CHIKV
      isolated from Ae. aegypti in Yemen. The larval container and Breteau indices in
      the visited localities surveyed were estimated at 53.8 and 100, respectively. The
      emergence of this unprecedented CHIKV epidemic in Al Hodayda is adding up another
      arboviral burden to the already existing vector-borne diseases. Considering the
      governorate as one focal port in the Red Sea region, the spread of the disease to
      other areas in Yemen and in neighboring countries is anticipated. Public health
      education and simple measures to detect and prevent mosquito breeding in water
      storage containers could prevent and reduce the spread of mosquito-borne viruses
      like CHIKV and DENV in Yemen.

PMID- 22469819
TI  - Bi-phasic nanostructures for functional applications.
AB  - Biphasic solid state composites of the type metal/metal oxide or element/element
      oxide can be synthesized in one pot chemical reactions using so called molecular
      "single source precursors". Due to their singular genesis these composites show
      peculiar hetero-structures based on core-shell hierarchies such as superlattices
      and composite nanospheres or nanowires. They exhibit superior or new functional
      properties compared to their individual constituent compounds. In the current
      work, we review in particular the synthetical and mechanistical approach of bi
      phasic (Al/Al(2)O(3)) nanostructures such as nanospheres, nanowires and nanoloops
      using a single source precursor. Other bi-phasic materials of the general formula
      M/MO(x) (for example M = Ge, Sn, Pb) are addressed for comparison. The impact of
      different synthetical conditions as well as of modification of surfaces by laser
      techniques and their technological relevance are presented briefly. Additionally,
      functional applications of the prepared surfaces are explained with some
      outstanding case studies. These case studies are primarily concerned with their
      use as biomaterials and their application in medicine as well as with their use
      as thin films for optics and functional surfaces.

PMID- 22469820
TI  - Comparison in antioxidant action between alpha-chitosan and beta-chitosan at a
      wide range of molecular weight and chitosan concentration.
AB  - Antioxidant activity in alpha- and beta-chitosan at a wide range of molecular
      weight (Mw) and chitosan concentration (CS) was determined by 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical scavenging activity, reducing ability, chelating
      ability, and hydroxyl radical scavenging activity. The form of chitosan (FC) had
      significant (P <0.05) effect on all measurements except DPPH radical scavenging
      activity, and antioxidant activity was dependent on Mw and CS. High Mw (280-300
      kDa) of beta-chitosan had extremely lower half maximal effective concentrations
      (EC(50)) than alpha-chitosan in DPPH radical scavenging activity and reducing
      ability. The 22-30 kDa of alpha- and beta-chitosan showed significantly (P <0.05)
      higher activities in DPPH radical scavenging, reducing ability, and hydroxyl
      radical scavenging than samples at other Mw, while chelating ability was the
      highest in 4-5 kDa chitosan. CS had significant effect on all measurements and
      the effect was related to Mw. The antioxidant activity of 280-300 kDa chitosan
      was affected by coil-overlap concentrations (C(*)) in the CS range of 4-10mg/mL,
      forming entanglements. Reducing ability and hydroxyl radical scavenging activity
      were more predominant action in antioxidant activity of chitosan as shown by the
      lower EC(50) values than those in other antioxidant measurements.

PMID- 22469821
TI  - Characterizing exposomes: tools for measuring personal environmental exposures.

PMID- 22469822
TI  - A further patient with van Maldergem syndrome.
AB  - We report on a male patient with the proposed diagnosis of the rare but very
      distinct entity of van Maldergem syndrome. His parents are first cousins. At the
      age of 4 years the boy presented with severe developmental delay, talipes
      equinovarus, finger camptodactyly with interphalangeal pterygium, joint laxity,
      bilateral microtia, and a dysmorphic facies. He showed bilateral epicanthus,
      telecanthus, short palpebral fissures, broad flat nasal bridge, and dental
      malocclusion. The combination of the specific facial features with camptodactyly,
      interphalangeal pterygium, joint laxity and developmental delay led to the
      diagnosis of van Maldergem syndrome. The medical history was further on
      significant for pharyngeal instability requiring the placement of a tracheostomy
      tube, an inguinal hernia, hip subluxation, small kidneys and genital
      abnormalities (micropenis, bifid scrotum, cryptorchidism). Due to severe feeding
      difficulties permanent tube feeding was required. Metabolic tests (newborn
      metabolic screening, 7-dehydrocholesterol, amino acids, organic acids in urine)
      and chromosomal analysis (450-500 bands; 46,XY) were normal. Molecular
      karyotyping revealed two parental CNVs (paternal deletion of 9q33.1; maternal
      duplication of 11p15.1), which are unlikely to contribute to the patient's
      phenotype. Taken together, the report on a further patient with van Maldergem
      syndrome expands the clinical spectrum of the condition by adding genital
      malformations, hernia, pharyngeal instability, and subluxation of the hip.

PMID- 22469823
TI  - Differential effects of TGF-beta1 and FGF-2 on SDF-1alpha expression in human
      periodontal ligament cells derived from deciduous teeth in vitro.
AB  - Stromal cell-derived factor (SDF)-1alpha has been reported to play a crucial role
      in stem cell homing and recruitment to injured sites. However, no information is
      available about its role in periodontal tissues. The aim of this in vitro study
      was to investigate the effects of basic fibroblast growth factor (FGF-2) and
      transforming growth factor (TGF)-beta1 on SDF-1alpha expression in immortalized
      periodontal ligament (PDL) cells derived from deciduous teeth (SH9 cells). Real
      time PCR and western blot analyses showed that SDF-1alpha mRNA expression in SH9
      cells was markedly inhibited by FGF-2 treatment for 48 h. SU5402, which directly
      interacts with the catalytic domain of the FGF receptor 1 (FGFR1) and suppresses
      its phosphorylation, inhibited the FGF-2-related decrease in SDF-1alpha
      expression. These results suggest that FGF-2 signaling via the FGFR1 pathway
      inhibits SDF-1alpha expression. Conversely, SDF-1alpha expression in SH9 cells
      was increased by TGF-beta1 treatment for 12 h. Western blot analysis showed that
      this treatment induced Smad2/3 phosphorylation. A time-course experiment showed
      that SDF-1alpha expression levels reached a maximum 12 h after the TGF-beta1
      treatment and returned to basal levels by 48 h. Real-time PCR analysis showed
      that Smad7 mRNA expression peaked by 6 h after TGF-beta1 treatment. Since Smad7
      siRNA downregulated Smad7 expression by approximately 2.5-fold compared with the
      negative control siRNA, the induction of SDF-1alpha expression was prolonged.
      Furthermore, treatment of SH9 cells with TGF-beta1 for 12 h induced transwell
      migration of UE7T-13 cells, which are mesenchymal stem cells derived from human
      bone marrow. Therefore, SDF-1alpha may play an important role in stem and
      progenitor cell recruitment and homing to injured sites in the periodontal
      ligament, and regulation of SDF-1alpha expression may be a useful tool in cell
      based therapy for periodontal tissue regeneration.

PMID- 22469824
TI  - Theoretical investigation of planar square carbon allotrope and its
      hydrogenation.
AB  - Using density functional theory we investigate a novel carbon allotrope 'SqC': a
      square planar material that can be more than tetracoordinated. Carbon atoms in
      this 2D square Bravais lattice form an unusual five-center four-electron bond
      with neighboring four carbon atoms (tetracoordination). Such an electron
      deficient bonding leaves an empty orbital which enables penta- or hexa
      coordinated carbon atom. Indeed, our simulations demonstrate such penta- and hexa
      coordinated configurations upon partial and complete hydrogenation, respectively.
      Surprisingly, in all the forms SqC shows the metallic character. SqC has the
      binding energy of 6.7 eV and it also satisfies the Born stability criteria. Yet
      our phonon calculations show that it may only be considered as quasi-stable.

PMID- 22469825
TI  - Stem cell biology: Towards the reality of cell therapeutics.
AB  - Although the road to cell therapeutics is rife with uncertainties - scientific,
      clinical and economic - its success could transform medicine. Five years into its
      mission, the California Institute of Regenerative Medicine is laying a foundation
      for this new form of medical treatment.

PMID- 22469826
TI  - Into the deep: Refocusing on 3D.

PMID- 22469827
TI  - A numbers game underpins cytoplasmic mRNA transport.
AB  - Microtubule-based mRNA transport participates in the establishment of cell
      asymmetries. An in vitro reconstitution assay demonstrates that localization
      signals present in an mRNA influence motor copy number on single RNA molecule
      cargoes, ultimately leading to highly polarized distributions of transcripts.

PMID- 22469828
TI  - Robustness in crossover regulation during meiosis.
AB  - Meiotic recombination produces physical linkages between homologous chromosomes
      that enable their segregation to opposite poles during meiosis I. In the absence
      of recombination, chromosomes mis-segregate, resulting in aneuploidy associated
      with severe birth defects. A recent study provides exciting insights into how
      recombination is fine-tuned to enforce a robust meiotic program.

PMID- 22469829
TI  - Twists and turns of invasion.
AB  - The transcription factor Twist1 is overexpressed in tumours and can induce the
      epithelial-mesenchymal transition, resulting in increased invasiveness. Twist1 is
      now shown to regulate cancer cell migration and invasion in three-dimensional
      environments by activating the RAC1 GTPase through suppression of a let-7
      microRNA family member.

PMID- 22469830
TI  - Signalling the end of the line.
AB  - Cellular senescence is a stable proliferation arrest induced by triggers such as
      short telomeres, activated oncogenes and genotoxic stress. Two studies show that
      cellular senescence induced by genotoxic stress depends on chronic DNA-damage
      signalling from irreparable damage to telomeres. Hence, dysfunctional or damaged
      telomeres are the initiators of multiple modes of senescence.

PMID- 22469835
TI  - Differential impact of nutrition on developmental and metabolic gene expression
      during fruiting body development in Neurospora crassa.
AB  - Fungal fruiting body size and form are influenced by the ecology of the species,
      including diverse environmental stimuli. Accordingly, nutritional resources
      available to the fungus during development can be vital to successful production
      of fruiting bodies. To investigate the effect of nutrition, perithecial
      development of Neurospora crassa was induced on two different media, a chemically
      sparsely nutritive Synthetic Crossing Medium (SCM) and a natural Carrot Agar
      (CA). Protoperithecia were collected before crossing, and perithecia were
      collected at 2, 24, 48, 72, 96, 120, and at full maturity 144 h after crossing.
      No differences in fruiting body morphology were observed between the two media at
      any time point. A circuit of microarray hybridizations comparing cDNA from all
      neighboring stages was performed. For a majority of differentially expressed
      genes, expression was higher in SCM than in CA, and expression of core metabolic
      genes was particularly affected. Effects of nutrition were highest in magnitude
      before crossing, lowering in magnitude during early perithecial development.
      Interestingly, metabolic effects of the media were also large in magnitude during
      late perithecial development, at which stage the lower expression in CA
      presumably reflected the continued intake of diverse complex initial compounds,
      diminishing the need for expression of anabolic pathways. However, for genes with
      key regulatory roles in sexual development, including pheromone precursor ccg-4
      and poi2, expression patterns were similar between treatments. When possible, a
      common nutritional environment is ideal for comparing transcriptional profiles
      between different fungi. Nevertheless, the observed consistency of the
      developmental program across media, despite considerable metabolic
      differentiation is reassuring. This result facilitates comparative studies that
      will require different nutritional resources for sexual development in different
      fungi.

PMID- 22469836
TI  - Estimation of central aortic systolic pressure using late systolic inflection of
      radial artery pulse and its application to vasodilator therapy.
AB  - BACKGROUND: Central blood pressure (BP) is a useful predictor of cardiovascular
      risk. Recently, a fully automated device that measures central SBP (cSBP) from
      radial late SBP (rSBP2) has been developed. METHOD: We measured cSBP using this
      device, compared it with aortic SBP (aSBP) measured with a high-fidelity pressure
      sensor, and evaluated the accuracy of cSBP before and after vasodilator
      administration. The data of 66 patients (mean age, 63.4 +/- 9.7 years; 49 men)
      who underwent cardiac catheterization were analyzed. The radial artery pulse
      waveform and brachial BP were measured sequentially and used to calculate cSBP.
      Brachial SBP and DBP were used for radial SBP (rSBP) and radial DBP to calculate
      the absolute value of rSBP2. The radial pulse waveform was recorded by an
      applanation tonometer (HEM-9000AI; Omron Healthcare Co. Ltd). A high-fidelity
      pressure sensor was placed in the ascending aorta, and aSBP was measured
      simultaneously by an invasive method. RESULTS: Significant positive correlations
      between directly measured aortic late SBP and cSBP or rSBP were observed (r =
      0.93, 0.88, respectively). Changes in aSBP before and after vasodilator
      administration showed a trend toward higher correlation with changes in cSBP than
      with changes in rSBP (r = 0.84, 0.78, respectively). The slope of the linear
      regression line of aSBP with cSBP (slope: 0.94) was closer to unity than with
      rSBP (0.66). CONCLUSION: Noninvasive cSBP calculated with rSBP2 accorded well
      with aSBP measured by the invasive method. Vasodilator medication and four of
      five diseases did not affect this relation.

PMID- 22469837
TI  - Development of structural kidney damage in spontaneously hypertensive rats.
AB  - The spontaneously hypertensive rat (SHR) is one of the major models of
      hypertension. This article describes the current state of knowledge about the
      mechanism behind kidney damage in SHR in the context of human hypertension and
      hypertensive kidney disease. It will argue that hypertensive damage in the SHR is
      pressure-dependent and shows how initial vascular damage leads to a loss of
      autoregulation and arterial hypertrophy in the juxtamedullary cortex while the
      outer cortical structures are relatively protected. Progressive arteriolar media
      hypertrophy then leads to the collapse of some glomeruli followed by tubular
      atrophy. The reduced glomerular filtration, thus, leads to compensatory
      hyperfiltration in another population of glomeruli which develop proteinuria and
      glomerulosclerosis. This model provides some important questions for future
      research. The regulation of media hypertrophy will be of great interest, as it
      might slow nephron loss and interstitial fibrosis. Finally, the mechanism by
      which reduced tubular flow leads to tubular atrophy is another important area for
      future research. Initial findings indicate that cilia activation may be of major
      importance for maintaining tubular structure.

PMID- 22469838
TI  - ESH position paper: renal denervation - an interventional therapy of resistant
      hypertension.
AB  - Experts from the European Society of Hypertension prepared this position paper in
      order to summarize current evidence, unmet needs and practical recommendations on
      the application of percutaneous transluminal ablation of renal nerves [renal
      denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant
      hypertension. The sympathetic nervous activation to the kidney and the sensory
      afferent signals to the central nervous system represent the targets of RND.
      Clinical studies have documented that catheter-based RDN decreases both efferent
      sympathetic and afferent sensory nerve traffic leading to clinically meaningful
      systolic and diastolic blood pressure (BP) reductions in patients with resistant
      hypertension. This position statement intends to facilitate a better
      understanding of the effectiveness, safety, limitations and issues still to be
      addressed with RDN.

PMID- 22469839
TI  - Downregulation of cylindromatosis gene, CYLD, confers a growth advantage on
      malignant melanoma cells while negatively regulating their migration activity.
AB  - The cylindromatosis gene (CYLD) encodes a deubiquitinase that was initially
      identified as a tumor suppressor and has recently been investigated in connection
      with a variety of normal physiological processes. In contrast to its cell
      proliferative activity, the effect of CYLD protein on cell migration has been a
      matter of debate. We investigated the effect of CYLD-siRNA on the migration
      activity of malignant melanoma cells. Expression of CYLD mRNA/protein was lower
      in 6 of 8 malignant melanoma cell lines than in 3 sets of primary-cultured normal
      human epidermal melanocytes. Knockdown of CYLD significantly increased the
      proliferation activities of two melanoma cell lines (p<0.05), along with BCL3
      nuclear translocation followed by CCND1 overexpression. In contrast to the
      proliferation-related activity, CYLD knockdown significantly decreased the cell
      migration of all the melanoma cell lines (n=7, p<0.05), and we demonstrated that
      the mechanism regulating melanoma cell migration was activation of RAC1 through
      the action of CYLD. Our findings provide new insight into the role of CYLD
      induced RAC1 activation in melanoma cell migration.

PMID- 22469840
TI  - Quercetin acts as an antioxidant and downregulates CYP1A1 and CYP1B1 against DMBA
      induced oxidative stress in mice.
AB  - We investigated the effects of quercetin on 7,12-dimethylbenz(a)anthracene (DMBA)
      induced oxidative stress and the expression of CYP1A1 and CYP1B1 in mice.
      Quercetin was administered orally to mice at 100 or 250 mg/kg BW for 18 days,
      after which DMBA (34 mg/kg BW) was administered intragastrically twice. Quercetin
      showed side effects such as increased aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) in DMBA-untreated mice. Also, quercetin induced
      AST and ALT in DMBA-treated, although this was not significantly different from
      levels in DMBA-treated controls. The thiobarbituric acid reactive substances
      (TBARS) value showed a tendency to decrease following quercetin treatment; these
      decreases were significantly greater in the DMBA-treated compared to the
      untreated groups. Also, catalase and superoxide dismutase (SOD) activities as
      well as their mRNA expression were increased by quercetin; this increase was more
      pronounced in DMBA-treated compared to untreated mice. DMBA induced CYP1 activity
      as well as expression of CYP1A1 and CYP1B1. Each of these effects was
      significantly reduced by quercetin; however, this reduction was observed for
      CYP1A1 at only the higher dose and for CYP1B1 at both doses. These data suggest
      that quercetin shows antioxidant activity against DMBA-induced oxidative stress.
      Moreover, its regulation of CYP1A1 and CYP1B1 suggests the potential of quercetin
      as an anticancer supplement.

PMID- 22469841
TI  - Effect of ascorbic acid and hydrogen peroxide on mouse neuroblastoma cells.
AB  - Ascorbic acid is one of the antioxidant compounds widely used against free
      radical stress. The present study was undertaken to examine whether ascorbic acid
      and hydrogen peroxide (H2O2), alone or in combination, could influence cell
      viability. The murine neuroblastoma cell line, N2a, was used to perform a dose
      response curve for ascorbic acid. It was observed that ascorbic acid alone at
      physiological concentrations (0.1-0.4 mM) did not cause any cell death. However,
      at pharmacological concentrations (1-6 mM), ascorbic acid caused dose-dependent
      cell death. The lethal concentration at which 50% cells were killed (LC50) was
      determined to be approximately 3.141 mM ascorbic acid at 24 h. H2O2 up to 300 uM
      alone did not cause significant cell death. In the combined treatment, when the
      cells were treated with ascorbic acid at physiological concentrations (0.4 mM)
      and H2O2 at 400 uM, higher rates of cell death were observed compared to the cell
      death rates caused by either compound alone. Subsequent experiments revealed that
      cell death was partly mediated through the loss of total glutathione levels in
      the cells. These data suggest that the combination of ascorbic acid and H2O2 is
      disadvantageous for cancer cell survival. Further studies are required to
      ascertain the physiological significance of these observations.

PMID- 22469842
TI  - Tif1gamma suppresses murine pancreatic tumoral transformation by a Smad4
      independent pathway.
AB  - Transcriptional intermediary factor 1gamma (TIF1gamma; alias,
      TRIM33/RFG7/PTC7/ectodermin) belongs to an evolutionarily conserved family of
      nuclear factors that have been implicated in stem cell pluripotency, embryonic
      development, and tumor suppression. TIF1gamma expression is markedly down
      regulated in human pancreatic tumors, and Pdx1-driven Tif1gamma inactivation
      cooperates with the Kras(G12D) oncogene in the mouse pancreas to induce
      intraductal papillary mucinous neoplasms. In this study, we report that aged Pdx1
      Cre; LSL-Kras(G12D); Tif1gamma(lox/lox) mice develop pancreatic ductal
      adenocarcinomas (PDACs), an aggressive and always fatal neoplasm, demonstrating a
      Tif1gamma tumor-suppressive function in the development of pancreatic
      carcinogenesis. Deletion of SMAD4/DPC4 (deleted in pancreatic carcinoma locus 4)
      occurs in approximately 50% of human cases of PDAC. We, therefore, assessed the
      genetic relationship between Tif1gamma and Smad4 signaling in pancreatic tumors
      and found that Pdx1-Cre; LSL-Kras(G12D); Smad4(lox/lox); Tif1gamma(lox/lox)
      (alias, KSSTT) mutant mice exhibit accelerated tumor progression. Consequently,
      Tif1gamma tumor-suppressor effects during progression from a premalignant to a
      malignant state in our mouse model of pancreatic cancer are independent of Smad4.
      These findings establish, for the first time to our knowledge, that Tif1gamma and
      Smad4 both regulate an intraductal papillary mucinous neoplasm-to-PDAC sequence
      through distinct tumor-suppressor programs.

PMID- 22469843
TI  - Quantification of the calcification phenotype of Abcc6-deficient mice with
      microcomputed tomography.
AB  - Pseudoxanthoma elasticum in humans and dystrophic cardiac calcification in mice
      are heritable disorders characterized by dystrophic calcification of soft
      connective tissues related to the defective function of the ABCC6 (human)/Abcc6
      (mouse) transporter. Of particular interest is the finding of calcified vibrissae
      in Abcc6(-/-) mice, which facilitates the study of dystrophic calcification by
      histological techniques. We aimed to determine whether mice prone to dystrophic
      cardiac calcification (C3H/HeOuJ and DBA/2J strains) presented similar vibrissae
      changes and to evaluate the value of microcomputed tomography to quantify the
      extent of mystacial vibrissae calcifications. These calcifications were absent in
      DBA/2J and C57BL/6J control mice. In both Abcc6(-/-) and C3H/HeOuJ mice,
      calcifications progressed in a caudal-rostral direction with aging. However, the
      calcification process was delayed in C3H/HeOuJ mice, indicating an incomplete
      expression of the calcification phenotype. We also found that the calcification
      process in the cephalic region was not limited to mystacial vibrissae but was
      also present in other periorbital sensorial vibrissae. The vibrissae
      calcification was circular and encompassed the medial region of the vibrissae
      capsule, adjacent to the ring and cavernous sinuses (the areas adjacent to blood
      and lymphatic vessels). Collectively, our findings confirm that Abcc6 acts as an
      inhibitor of spontaneous chronic mineralization and that microcomputed tomography
      is a valuable noninvasive tool for the assessment of the calcification phenotype
      in Abcc6-deficient mice.

PMID- 22469844
TI  - p53 and mitochondrial DNA: their role in mitochondrial homeostasis and toxicity
      of antiretrovirals.
AB  - The roles and actions of the tumor suppressor protein p53 have been extensively
      studied with regard to nuclear events, including transcription and DNA damage
      repair. However, the direct roles of p53 in mitochondrial DNA (mtDNA) replication
      and function are less well understood. Studies herein used a mitochondrial
      targeted p53 (MTS-p53) to determine its effects on both mtDNA abundance and
      mitochondrial function. MTS-p53 decreased cellular proliferation and mtDNA
      abundance in HepG2 cells transfected with wild-type (WT) human p53. When MTS-p53
      cells were treated with the nucleoside reverse transcriptase inhibitor (NRTI),
      2',3'-dideoxycytidine or 2',3'-dideoxyinosine, mtDNA depletion that resembled
      untransfected controls was observed in both instances. p53-Overexpressing cells
      showed reduced mitochondrial function by oximetry, including a reduction in
      maximal respiratory capacity and reserve capacity. A truncated p53 (MTS-p53-290)
      was generated for localization exclusively to the mitochondria. MTS-p53-290 cells
      proliferated at control levels but displayed decreased mtDNA abundance and
      mitochondrial function with NRTI treatment. The MTS-p53-290 cells demonstrated
      that only the nuclear fraction of p53 controlled cellular proliferation, which
      was supported by the MTS-p53 results. Data herein indicate that overexpression of
      p53 in the mitochondria reduces mtDNA abundance and increases the sensitivity of
      mammalian cells to NRTI exposure by reducing mitochondrial function.

PMID- 22469845
TI  - T2* mapping of hip joint cartilage in various histological grades of
      degeneration.
AB  - OBJECTIVE: To evaluate T2* values in various histological severities of
      osteoarthritis (OA). METHOD: Magnetic resonance imaging (MRI) and T2* mapping
      including a three-dimensional (3D) double-echo steady-state (DESS) sequence for
      morphological cartilage assessment and a 3D multiecho data image combination
      (MEDIC) sequence for T2* mapping were conducted in 21 human femoral head
      specimens with varying severities of OA. Subsequently, histological assessment
      was undertaken in all specimens to correlate the observations of T2* mapping with
      histological analyses. According to the Mankin score, four grades of histological
      changes were determined: grade 0 (Mankin scores of 0-4), grade I (scores of 5-8),
      grade II (scores of 9-10), and grade III (scores of 11-14). For reliability
      assessment, cartilage T2* measurements were repeated after 4 weeks in 10 randomly
      selected femoral head specimens. RESULTS: T2* values decreased significantly with
      increasing cartilage degeneration (total P-values <0.001) ranging from 36.3 +/-
      4.3 ms in grade 0 regions to 22.8 +/- 4.3 ms in regions with grade III changes.
      Pearson correlation analysis proved a fair correlation between T2* values and
      Mankin score (correlation coefficient = -0.362) that was statistically
      significant (P-value <0.001). Intra-class correlation (ICC) analysis demonstrated
      high intra-observer reproducibility for the T2* measurement (ICC: 0.949, P <
      0.001). CONCLUSIONS: Given the advantages of the T2* mapping technique with no
      need for contrast medium, high image resolution and ability to perform 3D
      biochemically sensitive imaging, T2* mapping may be a strong addition to the
      currently evolving era of cartilage biochemical imaging.

PMID- 22469846
TI  - The early outcome of surgical treatment for femoroacetabular impingement: success
      depends on how you measure it.
AB  - OBJECTIVE: To evaluate the proportion of "successes" after surgery for
      femoroacetabular impingement (FAI) using different external criteria, "feeling
      better" and "feeling good", and to determine the corresponding cut-off scores
      indicating "success" for the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) (0-10-point response scale), Oxford Hip Score (OHS)
      and EuroQoL-5D (EQ-5D and EQ-VAS). DESIGN: Prospective, observational study based
      in an orthopaedic hospital. Ninety-nine consecutive patients with FAI completed
      the questionnaires before and 6 months after surgery (arthroscopy or mini-open
      surgical dislocation). Patient-ratings of change in state ("feeling better") were
      assessed using a global treatment outcome (GTO) item. Acceptability of the
      current health state was assessed using the symptom-specific well-being (SSWB)
      item. Cut-off (threshold) scores for the different instruments indicating the
      minimal clinically important change (MCIC) and acceptable symptom state were
      calculated using Receiver Operating Characteristics (ROC) analyses. RESULTS:
      Significant improvements in all scores (P < 0.001) were recorded 6 months after
      surgery. The proportion of good outcomes measured with GTO was 60%; 55% of
      patients reported having achieved an acceptable symptom state. The MCIC scores
      for improvement were >=6 for the OHS (0-48 total score range), >=15 for EQ-VAS,
      >=0.16 for EQ-5D index, and >=22 for the WOMAC-total score (0-100 total score
      range); absolute scores of >=40, >=80, >=0.682 and <=8, respectively, were
      associated with an acceptable symptom state. CONCLUSIONS: The results show that
      feeling better does not always equate to feeling good, and that improvements in
      outcome scores, even large, do not necessarily indicate acceptability of the
      current state. The cut-off values may help in the interpretation of trial results
      and individual change-scores recorded in clinical practice.

PMID- 22469847
TI  - Measurement of matrilin-3 levels in human serum and synovial fluid using a
      competitive enzyme-linked immunosorbent assay.

PMID- 22469848
TI  - Patterns of joint damage seen on MRI in early hip osteoarthritis due to
      structural hip deformities.
AB  - OBJECTIVE: The aim of this study was to evaluate differences in damage patterns
      assessed using magnetic resonance imaging (MRI) between hips with
      femoroacetabular impingement (FAI) and developmental dysplasia of the hip (DDH)
      as well as to correlate MRI findings with delayed Gadolinium enhanced MRI of
      cartilage (dGEMRIC) and with patient pain. DESIGN: This retrospective study
      included 40 patients (mean age 28.6 +/- 11.2 years) who underwent dGEMRIC and
      morphological MRI of the hip. Twenty-one hips with FAI and 19 with DDH were
      investigated. A self-developed morphological grading (MRI score) and dGEMRIC
      evaluation were done on seven radial reformats obtained from an isotropic 3D True
      fast imaging with steady state precession (FISP) sequence and an isotropic T1
      mapping sequence. The observed damage patterns were summed up into sub-scores and
      a total MRI score. RESULTS: Labrum damage, paralabral cysts, and acetabular rim
      bone cysts were more common in DDH patients than in FAI patients. No significant
      differences were seen in the occurrence of cartilage damage, bone cysts, or
      osteophytes. In DDH (but not in FAI), the dGEMRIC index demonstrated a tendency
      for lower values in areas next to cartilage defects. There was no association
      between labrum damage and dGEMRIC index. A moderate correlation was seen between
      Western Ontario and McMaster Universities (WOMAC) pain score and cartilage
      damage, paralabral cysts, and the total MRI score. CONCLUSIONS: This study
      confirms a higher prevalence of labrum damage but not cartilage damage in
      patients with DDH in comparison to patients with FAI. In addition, our data
      suggests an association of cartilage damage and paralabral cysts with patient
      reported pain.

PMID- 22469849
TI  - Usefulness of specific OA biomarkers, Coll2-1 and Coll2-1NO2, in the anterior
      cruciate ligament OA canine model.

PMID- 22469850
TI  - Chondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a
      cluster-randomized, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of chondroitin sulfate and/or
      glucosamine hydrochloride in alleviating symptoms and improving the dysfunction
      of Kashin-Beck disease (KBD) patients. METHODS: We undertook a cluster
      randomized, placebo-controlled trial in 251 patients with KBD. Participants were
      randomly allocated to comparing (1) chondroitin sulfate, (2) glucosamine
      hydrochloride, (3) a combination of chondroitin sulfate and glucosamine
      hydrochloride, or (4) placebo, for 6 months duration. The primary outcome
      measures of interest were 20% and 50% reductions in pain from baseline, measured
      by pain subscale in the Western Ontario and McMaster Universities Osteoarthritis
      (WOMAC) Index. Secondary outcome measures included parameters in the WOMAC Index
      such as pain, stiffness, and physical function, as well as patients' quality of
      life by the 12-item Short-Form General Health Survey. The trial registration
      number is ChiCTR-TRC-11001480 (http://www.chictr.org/). RESULTS: A combination
      therapy of chondroitin sulfate and glucosamine hydrochloride was effective in
      reducing WOMAC pain by 20% (differences of 23.4%, P=0.006) and 50% (differences
      of 15.7%, P=0.016), WOMAC pain (P=0.032), WOMAC stiffness (P=0.043), and WOMAC
      total score (P=0.035). Chondroitin sulfate used alone was also found to be
      effective in reducing WOMAC total score and stiffness score (P=0.038 and P=0.023,
      respectively). No significant positive effects in improving WOMAC Index scores
      were observed with glucosamine hydrochloride alone. CONCLUSION: The findings of
      this study indicate that a combination of chondroitin sulfate and glucosamine
      hydrochloride was more effective than placebo in treating KBD.

PMID- 22469851
TI  - Enhanced levels of non-enzymatic glycation and pentosidine crosslinking in
      spontaneous osteoarthritis progression.
AB  - OBJECTIVE: To test the hypothesis that heightened advanced glycation endproducts
      (AGEs) content in cartilage accelerates the progression of spontaneous
      osteoarthritis (OA) in the Hartley guinea pig (HGP) model. METHODS: Twenty-eight
      male, 3-month-old HGPs were used. Eight were left untreated as a baseline control
      group and sacrificed at 3 months of age (n = 4) and 9 months of age (n = 4; age
      matched controls). The other 20 HGPs received intra-articular knee injections in
      the right knee whereas the left knees acted as contra-lateral non-injected
      controls. Injections consisted of 100 MUl phosphate buffered saline (PBS; n = 10)
      or PBS+2.0 M D-(-)-Ribose (n = 10). Injections were given once weekly for 24
      weeks. At the end of the treatment period, the tibiae were fixed with formalin,
      scanned with microCT for sub-chondral bone mineral density, and then histological
      slides were prepared, stained with Safranin-O with Fast Green counter stain and
      scored using the OARSI-HISTOgp scheme. Cartilage pentosidine (established
      biomarker for AGEs) content, collagen content (% dry mass), glucosaminoglycan GAG
      to-collagen ratio (MUg/MUg), GAG-to-DNA ratio and DNA-to-collagen ratio were
      measured. RESULTS: Pentosidine content increased greatly due to PBS + Ribose
      injection (P < 0.0001) and reached levels found in cartilage from 80-year-old
      humans. Surprisingly, mean OARSI-HISTOgp scores for both the injected and contra
      lateral controls in the PBS + Ribose group were not detectably different, nor
      were they different from the mean score for the age-matched control group.
      CONCLUSION: AGEs accumulation due to intra-articular ribose-containing injections
      in the HGP model of spontaneous knee OA did not enhance disease progression.

PMID- 22469852
TI  - Three-dimensional patterns of early acetabular cartilage damage in hip dysplasia;
      a high-resolutional CT arthrography study.
AB  - OBJECTIVE: The purpose of this study was to examine the three-dimensional (3D)
      progression patterns of early acetabular cartilage damage in hip dysplasia using
      high-resolutional computed tomography (CT) arthrography. DESIGN: Thirty-two
      dysplastic hips of 26 Japanese symptomatic females including 21 hips in pre-stage
      of osteoarthritis (Kellgren-Lawrence (K-L) grade 0; mean patient age, 32.0 years)
      and 11 hips in early stage of osteoarthritis (K-L grade 1 or 2; mean patient age,
      32.8 years) were examined. Isotropic high-resolutional CT arthrography with an
      image resolution of 0.5 mm in any orthogonal direction was performed. A 3D
      acetabular cartilage model was generated and we evaluated distribution of
      cartilage thickness in 12 zones after dividing the weight-bearing area of the hip
      joint in radial and lateral/medial directions. RESULTS: In pre-stage of
      osteoarthritis, significant differences in cartilage thickness were observed
      between the lateral and medial zones in all radial regions, most prominently in
      the antero-superior region. In early stage of osteoarthritis, no significant
      differences in cartilage thickness were observed, except in the most posterior
      region. The lateral-medial (LM) ratio was defined as cartilage thickness in the
      lateral zone divided by that in the medial zone, and hips with the LM ratio in
      the antero-superior region of <1.4 had significantly more extensive involvement
      of labral tears than hips with the LM ratio of >=1.4. CONCLUSIONS: In hip
      dysplasia, acetabular cartilage damage was probably occurred in the antero
      superior lateral area. The LM ratio may be a sensitive index to quantify early
      cartilage damage associated with extent of labral disorders.

PMID- 22469853
TI  - Activation of Indian hedgehog promotes chondrocyte hypertrophy and upregulation
      of MMP-13 in human osteoarthritic cartilage.
AB  - OBJECTIVE: The objectives of this study were to (1) determine the correlation
      between osteoarthritis (OA) and Indian hedgehog (Ihh) expression, and (2)
      establish the effects of Ihh on expression of markers of chondrocyte hypertrophy
      and matrix metalloprotease (MMP)-13 in human OA cartilage. DESIGN: OA cartilage
      and synovial fluid samples were obtained during total knee arthroplasty. Normal
      cartilage samples were obtained from intra-articular tumor resections, and normal
      synovial fluid samples were obtained from healthy volunteers and the
      contralateral uninjured knee of patients undergoing anterior cruciate ligament
      reconstruction. OA was graded using the Mankin score. Expression of Ihh in
      synovial fluid was determined by Western blot. Ihh, type X collagen and MMP-13
      mRNA were determined by real time PCR. Protein expression of type X collagen and
      MMP-13 in cartilage samples was analyzed with immunohistochemistry. Chondrocyte
      size was measured using image analysis. RESULTS: Ihh expression was increased 2.6
      fold in OA cartilage and 37% in OA synovial fluid when compared to normal control
      samples. Increased expression of Ihh was associated with the severity of OA and
      expression of markers of chondrocyte hypertrophy: type X collagen and MMP-13, and
      chondocyte size. Chondrocytes were more spherical with increasing severity of OA.
      There was a significant correlation between Mankin score and cell size (r(2) =
      0.80) and Ihh intensity (r(2) = 0.89). Exogenous Ihh induced a 6.8 fold increase
      of type X collagen and 2.8 fold increase of MMP-13 mRNA expression in cultured
      chondrocytes. Conversely, knockdown of Ihh by siRNA and Hh inhibitor cyclopamine
      had the opposite effect. CONCLUSIONS: Ihh expression correlates with OA
      progression and changes in chondrocyte morphology and gene expression consistent
      with chondrocyte hypertrophy and cartilage degradation seen in OA cartilage.
      Thus, Ihh may be a potential therapeutic target to prevent OA progression.

PMID- 22469854
TI  - Synthesis and antitumor activity of inositol phosphotriester analogues.
AB  - Inositol phosphates, as important second messengers of signal transduction,
      regulate many biological functions. However, cell penetration and phospholipase
      stability could be two main issues faced by inositol phosphate analogues used as
      lead compounds for drug discovery. Inositol phosphotriester analogues could be
      more beneficial to diffuse across plasma membrane. In this paper, we describe the
      design and synthesis of a series of inositol phosphotriester analogues based on
      phosphatidylinositol, along with the initial antitumor activity analysis. Several
      compounds exhibited good cytotoxic activity against human cancer cell lines A549,
      HepG2, MDA-MB-231 and HeLa, especially compound 33 was cytotoxic against all the
      four cancer cell lines with good IC(50) values.

PMID- 22469855
TI  - The value of bodily material: acquiring and allocating human gametes.
AB  - The UK is facing increasing demand for sperm and eggs for use in medical
      treatment and research. The disparity between supply and demand has led a number
      of UK bodies to recommend the adoption of a national donation system, at least
      with regard to gamete donation for treatment. This article argues that a national
      gamete donation system would have benefits beyond those articulated by bodies
      such as the Human Fertilisation and Embryology Authority, the British Fertility
      Society, and the Nuffield Council on Bioethics, because a system of this type
      could facilitate the legal and ethical implementation of donor incentives. Three
      types of incentive are explored and it is argued that a national donation system
      could and should be utilised to implement a mirror exchange scheme or,
      preferably, an indirect mirror exchange scheme.

PMID- 22469856
TI  - In vitro and in vivo osteogenesis of human mesenchymal stem cells derived from
      skin, bone marrow and dental follicle tissues.
AB  - The present study evaluated the human mesenchymal stem cells (hMSCs) isolated
      from skin (hSMSC), bone marrow (hBMSC) and dental follicle (hDFMSC) tissues on
      their in vitro and in vivo osteogenic potential using demineralized bone matrix
      (DBM) and fibrin glue scaffold. Cells originated from three distinct tissues
      showed positive expressions of CD44, CD73, CD90, CD105 and vimentin, and
      differentiation ability into osteocytes, adipocytes and chondrocytes. hMSCs from
      all tissues co-cultured with a mixed DBM and fibrin glue scaffold in non
      osteogenic induction media were positively stained by von Kossa and expressed
      osteoblast-related genes, such as osteocalcin (OC), osteonectin (ON), runt
      related transcription factor 2 (Runx2) and osterix. For in vivo osteogenic
      evaluation, PKH26 labeled hMSCs were implanted into the subcutaneous spaces of
      athymic mice with a mixed scaffold. At 4 weeks of implantation, PKH26 labeled
      cells were detected in all hMSC-implanted groups. Bone formation with OC
      expression and radio-opacity intensity were observed around DBM scaffold in all
      hMSC-implanted groups. Interestingly, hDFMSCs-implanted group showed the highest
      OC expression and calcium content. These findings demonstrated that hDFMSCs could
      be a potential alternative autologous cell source for bone tissue engineering.

PMID- 22469857
TI  - The effect of the NF-kappa B inhibitors curcumin and lactacystin on myogenic
      differentiation of rhabdomyosarcoma cells.
AB  - Rhabdomyosarcoma is a soft tissue sarcoma mainly seen in children. Despite
      considerable progress within the last few years, therapeutic approaches for this
      type of tumor are still limited. The respective tumor cells originate from
      myogenic precursor cells and are characterized by a blockade in their
      differentiation program. Interestingly, there is a direct inverse correlation
      between the differentiation status of a specific rhabdomyosarcoma cell and its
      metastatic potential. Thus, here, we tested whether the ubiquitous transcription
      factor NF-kappaB, which regulates myogenic differentiation and is also a
      promising therapeutic target in the treatment of other types of tumors, might be
      an interesting candidate for the development of novel rhabdomyosarcoma treatment
      strategies. For this purpose, we analyzed NF-kappaB activity (classical pathway)
      in myoblasts with different differentiation potential, specifically in three
      different rhabdomyosarcoma cell lines. In addition, we inhibited NF-kappaB
      activity in these cells and analyzed the effects on myogenic differentiation. We
      show that after the induction of differentiation, NF-kappaB activity declines
      rapidly in normal myoblasts, but only slightly in rhabdomyosarcoma cells.
      However, after treatment of the cells with two different small-molecule NF-kappaB
      inhibiting compounds, the IKK inhibitor curcumin and the proteasome inhibitor
      lactacystin, we found that neither curcumin nor lactacystin promoted myogenic
      differentiation in either normal myoblasts or rhabdomyosarcoma cells. Taken
      together, our data suggest that treatment with curcumin or lactacystin might not
      be a suitable approach in the treatment of rhabdomyosarcoma.

PMID- 22469858
TI  - Emerging technologies in mass spectrometry imaging.
AB  - Mass spectrometry imaging (MSI) as an analytical tool for bio-molecular and bio
      medical research targets accurate compound localization and identification. In
      terms of dedicated instrumentation, this translates into the demand for more
      detail in the image dimension (spatial resolution) and in the spectral dimension
      (mass resolution and accuracy), preferably combined in one instrument. At the
      same time, large area biological tissue samples require fast acquisition schemes,
      instrument automation and a robust data infrastructure. This review discusses the
      analytical capabilities of an "ideal" MSI instrument for bio-molecular and bio
      medical molecular imaging. The analytical attributes of such an ideal system are
      contrasted with technological and methodological challenges in MSI. In
      particular, innovative instrumentation for high spatial resolution imaging in
      combination with high sample throughput is discussed. Detector technology that
      targets various shortcomings of conventional imaging detector systems is
      highlighted. The benefits of accurate mass analysis, high mass resolving power,
      additional separation strategies and multimodal three-dimensional data
      reconstruction algorithms are discussed to provide the reader with an insight in
      the current technological advances and the potential of MSI for bio-medical
      research.

PMID- 22469859
TI  - Another piece of the obesity-environment puzzle: potential link between
      inflammation and POP-associated metabolic diseases.

PMID- 22469860
TI  - Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated
      influenza vaccine in children 12-59 months of age previously given AS03
      adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network
      (PCIRN) study.
AB  - BACKGROUND: Concern arose in 2010 that reactogenicity, particularly febrile
      seizures, to influenza A/H1N1-containing 2010-2011 trivalent seasonal inactivated
      influenza vaccine (TIV) could occur in young children who had been previously
      immunized and/or infected with the pandemic strain. We conducted a pre-season
      study of 2010-2011 TIV safety and immunogenicity in children 12-59 months of age
      to inform public health decision making. METHODS: Children immunized with 1 or 2
      doses of the pandemic vaccine, with or without the 2009-10 TIV, received 1 or 2
      doses of 2010-11 TIV in an observational, multicentre Canadian study. Standard
      safety monitoring was enhanced by a telephone call at ~24 h post-TIV when adverse
      events were expected to peak. Summary safety reports were rapidly reported to
      public health before the launch of public programs. TIV immunogenicity was
      assessed day 0, and 21 days after final vaccination. Clinical Trials Registration
      NCT01180621. RESULTS: Among 207 children, a general adverse event was reported by
      60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever
      (>38.5 degrees C) was more common in two-dose compared to one dose recipients
      (16.7%, n=4 v. 1.0%, n=2). At baseline 99.0% of participants had A/H1N1
      hemagglutinin inhibition (HAI) titers >=10, and 85.5% had a protective titer of
      >=40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in
      recipients of a 2-dose schedule of pandemic vaccine compared to one-dose
      recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, p<0.001). At 21
      days, all regulatory criteria for influenza vaccine immunogenicity were exceeded
      for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations
      between reactogenicity and either baseline high influenza titers or serologic
      response to revaccination were evident. CONCLUSIONS: Infants and toddlers who
      received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained
      high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in
      TIV resulted in no unusual adverse effects and 100% were sero-protected for
      A/H1N1 after receipt of the 2010-11 TIV.

PMID- 22469861
TI  - Enhancement of the immunogenicity of an alphavirus replicon-based DNA vaccine
      against classical swine fever by electroporation and coinjection with a plasmid
      expressing porcine interleukin 2.
AB  - Alphavirus replicon-based DNA vaccines have emerged as a promising approach to
      generation of antigen-specific immune responses. However, due to their low
      immunogenicity, there is a need for other approaches to enhance the vaccine
      potency. In this study, electroporation (EP) and a plasmid expressing porcine
      interleukin 2 (IL-2) were used to improve the immunogenicity of an alphavirus
      replicon-based DNA vaccine pSFV1CS-E2 against classical swine fever (CSF). Pigs
      were immunized with pSFV1CS-E2 alone or together with IL-2 by EP or by simple
      intramuscular injection. The results showed that EP combined with IL-2 resulted
      in marked enhancement of E2-specific antibody responses. Moreover, CSFV-specific
      lymphocyte proliferation, IFN-gamma and IL-4 responses were increased
      significantly in the pSFV1CS-E2+IL-2/EP group. Pigs immunized with pSFV1CS-E2
      plus IL-2 by EP were completely protected from lethal challenge, which is
      comparable to the sterilizing immunity and full protection offered by the live
      attenuated vaccine C-strain and in contrast with the incomplete protection
      conferred by pSFV1CS-E2 without or with IL-2 or EP alone, as demonstrated by the
      presence of pathological changes or/and viral loads. We conclude that EP in
      combination with IL-2 can significantly improve the immunogenicity of the plasmid
      DNA vaccine.

PMID- 22469862
TI  - Assessment of inactivated human rabies vaccines: biochemical characterization and
      genetic identification of virus strains.
AB  - The World Health Organization (WHO) recommends the periodic evaluation of the
      purity of the cell lines used in the production of rabies vaccines, as well as
      the antigenic identity of the virus strains. Here, we analyzed seventeen marketed
      inactivated human rabies virus vaccines for viral and non-viral proteins by SDS
      PAGE and Coomassie/silver staining. Mass spectrometric analysis of an abundant 60
      70 kDa signal indicated that in most vaccines serum albumin of human origin (HSA)
      was the major component. Quantification of HSA in the vaccines revealed a mean
      concentration of 22 mg HSA/dose in all tested PVRV (purified vero cell rabies
      vaccine), HDCV (human diploid cell rabies vaccine) and PHK (primary hamster
      kidney) vaccines. In contrast, 1000-fold lower HSA levels and no HSA were
      detected in PCECV (purified chick embryo cell-culture vaccine) and PDEV (duck
      embryo rabies vaccine), respectively. Western blot analyses further confirmed a
      high bias in the HSA content, whereas the virus protein levels were rather
      similar in all tested vaccines. In addition, the vaccine viruses were sequenced
      within the N- and G-genes to identify the strain. In the majority of sequenced
      vaccines, the declared vaccine strain was confirmed. However, some discrepancies
      in the genetic identification were observed, supporting WHO's recommendation for
      the molecular characterization of vaccine seed strains. This research highlights
      the variation in purity found between different human rabies virus vaccines, and
      suggests that further research is needed to establish the impact non-active
      components have on the potency of such vaccines.

PMID- 22469863
TI  - Age of recipient and number of doses differentially impact human B and T cell
      immune memory responses to HPV vaccination.
AB  - Vaccination is one of the most effective medical interventions. However,
      optimization of existing as well as design of new vaccines is still mostly
      conducted empirically; a rational approach to vaccine design is largely
      prohibited by the lack of insight into the relevant mechanisms underlying immune
      mediated protection. To delineate the impact of variables on immune memory
      formation following vaccination, we took advantage of a trial assessing the role
      of the age of the recipient and the number of administered doses of the
      quadrivalent HPV vaccine in a well-characterized longitudinal cohort of girls and
      young women. We found that age of the recipient and the number of doses
      administered differentially impact the development of B and T cell memory.
      Specifically, age of the recipient significantly impacted generation of HPV 18
      specific B cell memory, while the number of vaccine doses displayed a significant
      effect on the development of HPV-specific T cell memory. Our data indicate that
      rational design of vaccines has to be tailored according to the desired induction
      of B and/or T cell memory.

PMID- 22469864
TI  - Immunogenicity and specificity of norovirus Consensus GII.4 virus-like particles
      in monovalent and bivalent vaccine formulations.
AB  - Noroviruses, a major cause of acute gastroenteritis worldwide, present antigenic
      diversity that must be considered for the development of an effective vaccine. In
      this study, we explored approaches to increase the broad reactivity of virus-like
      particle (VLP) norovirus vaccine candidates. The immunogenicity of a GII.4
      "Consensus" VLP that was engineered from sequences of three genetically distinct
      naturally occurring GII.4 strains was examined for its ability to induce cross
      reactive immune responses against different clusters of GII.4 noroviruses.
      Rabbits immunized with GII.4 Consensus VLPs developed high serum antibody titers
      against VLPs derived from a number of distinct wild-type GII.4 viruses, including
      some that had been circulating over 30 years ago. Because the sera exhibited low
      cross-reactivity with antigenically distinct GI norovirus strains, we
      investigated the serum antibody response to a bivalent vaccine formulation
      containing GI.1 (Norwalk virus) and GII.4 Consensus VLPs that was administered to
      animals under varying conditions. In these studies, the highest homologous and
      heterologous antibody titers to the bivalent vaccine were elicited following
      immunization of animals by the intramuscular route using Alhydrogel (Al(OH)(3))
      as adjuvant. Our data indicate that the use of both genetically engineered
      norovirus VLPs that incorporate relevant epitopes from multiple strains and
      multivalent vaccine formulations increase the breadth of the immune response to
      diverse variants within a genotype and, thus, prove helpful in the rational
      design of VLP-based vaccines against human noroviruses.

PMID- 22469865
TI  - DOI-induced deficits in prepulse inhibition in Wistar rats are reversed by
      mGlu2/3 receptor stimulation.
AB  - Prepulse inhibition (PPI) of the acoustic startle response (ASR) provides a
      measure of sensorimotor gating mechanisms that are impaired in schizophrenia
      patients. Interactions of the serotonin (5-hydroxytryptamine, 5-HT) and
      glutamatergic systems, especially via the 5-HT(2A) receptor subtype, have been
      implicated in the regulation of PPI. The present study investigated the
      involvement of interactions between 5-HT(2A) and metabotropic glutamate (mGlu)2/3
      receptors in modulating PPI in Wistar and Lister Hooded rats. Systemic
      administration of the 5-HT(2A/2C) receptor agonist DOI ((+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropan hydrochloride; 3mg/kg) reduced PPI and ASR magnitude in
      Wistar but not in Lister Hooded rats. In Wistar rats, pre-treatment with the
      mGlu2/3 receptor agonist LY379268 (1mg/kg) attenuated the DOI-induced disruption
      of PPI as well as the DOI-elicited reductions of ASR magnitude. LY379268 itself
      did not alter PPI in both strains and only slightly increased ASR magnitudes in
      Wistar rats. Taken together, these findings support the notion of functionally
      antagonistic interactions between 5-HT(2A) and mGlu2/3 which might be involved in
      regulating sensorimotor gating mechanisms. Additionally, the data suggest that
      stimulation of mGlu2/3 receptors may be useful to ameliorate sensorimotor gating
      deficits resulting from an overstimulation of 5-HT(2A) receptors.

PMID- 22469866
TI  - Differential effects of the antidepressant mirtazapine on amphetamine- and
      dizocilpine-induced PPI deficits.
AB  - Prepulse inhibition (PPI) refers to the decrease in motor startle response to
      salient sensory stimuli (pulses) when they are closely preceded in time by
      another more modest sensory stimulus (prepulse). PPI deficits can be induced by
      stimulation of dopamine receptors (e.g., amphetamine or apomorphine) or blockade
      of NMDA glutamate receptors (e.g., dizocilpine or PCP). Previously we found that
      antagonists of alpha(2)-noradrenergic and H(1)-histaminergic receptors
      significantly attenuate PPI impairments caused by amphetamine or dizocilpine. In
      the current study we assessed the effects of the antidepressant mirtazapine,
      which has combined antagonist effects at alpha(2)-noradrenergic, H(1)
      histaminergic and 5-HT serotonergic receptors, on amphetamine- and dizocilpine
      induced PPI deficits. In Experiment 1, rats were tested for PPI of the startle
      response to a tactile air-puff stimulus after auditory prepulses of three
      different intensities. Drug treatments consisted of combinations of amphetamine
      (0 and 1mg/kg) and mirtazapine (0, 0.5, 1, 2, and 5mg/kg), with all rats
      receiving all drug doses and combinations with different counterbalanced orders.
      In Experiment 2, a different group of rats was tested with drug treatments
      consisting of combinations of dizocilpine (0 and 0.05 mg/kg) and mirtazapine (0,
      0.5, 1, 2, and 5 mg/kg). In Experiment 1 amphetamine (1 mg/kg) significantly
      reduced PPI whereas mirtazapine caused the opposite effect, with the highest dose
      of mirtazapine (5 mg/kg) effectively reversing the amphetamine-induced PPI
      deficit. In Experiment 2 dizocilpine (0.05 mg/kg) significantly reduced PPI, but
      mirtazapine did not have a significant effect on the inhibition of the startle
      response. These results indicate that the potential beneficial effects of
      combined alpha-adrenergic, 5-HT, and H(1) receptor blockade in counteracting PPI
      deficits may be associated to cases of sensorimotor gating disorders mediated by
      dopamine, but not necessarily to NMDA glutamate-induced PPI impairments.

PMID- 22469867
TI  - Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non
      alcoholic steatohepatitis using FLS-ob/ob male mice.
AB  - Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a metabolic
      syndrome characterized by accumulation of hepatic fat, inflammation and varying
      degrees of fibrosis. Angiotensin (AT)-II has been reported to play a role in the
      establishment of NASH. This study examined the effects of an AT-II receptor
      blocker, irbesartan, on NASH using fatty liver Shionogi (FLS)-ob/ob male mice as
      the closest animal model of human metabolic syndrome-related NASH. Irbesartan (30
      mg/kg/day) was orally administered to FLS-ob/ob mice for 12 weeks (irbesartan
      group). The effects of irbesartan on steatohepatitis were examined using factors
      including steatosis, fibrosis, inflammation and oxidative stress. The areas of
      hepatic fibrosis and hepatic hydroxyproline content were significantly lower in
      the irbesartan group compared to controls. The areas of alpha-smooth muscle actin
      positivity and F4/80-positive cells were significantly decreased in the
      irbesartan group. The percentage of 8-hydroxy-2-deoxyguanosine (8-OHdG)-positive
      cells and 8-OHdG DNA content were significantly decreased in the irbesartan group
      compared to controls. Levels of RNA expression for procollagen I, transforming
      growth factor beta1, tumor necrosis factor-alpha, sterol regulatory element
      binding protein 1c and fatty acid synthase were significantly lower in the
      irbesartan group compared to controls. In contrast, the gene expression of
      peroxisome proliferator activated receptor-alpha was significantly higher in the
      irbesartan group compared to controls. Irbesartan administration improved hepatic
      steatosis and attenuated the progression of hepatic fibrosis by inhibiting the
      activation of hepatic stellate cells and Kupffer cells and reducing oxidative
      stress.

PMID- 22469868
TI  - Fully automated synthesis of PET TSPO radioligands [11C]DAA1106 and
      [18F]FEDAA1106.
AB  - [(11)C]DAA1106 was prepared by O-[(11)C]methylation of DAA1123 with
      [(11)C]CH(3)OTf and NaH in CH(3)CN at 80 degrees C and isolated by HPLC combined
      with SPE purification in 60-70% decay corrected radiochemical yield.
      [(18)F]FEDAA1106 was synthesized by the nucleophilic substitution of tosyloxy
      FEDAA1106 in DMSO with K[(18)F]F/Kryptofix 2.2.2 at 140 degrees C and isolated by
      HPLC combined with SPE purification in 30-60% decay corrected radiochemical
      yield. The specific activity for [(11)C]DAA1106 and [(18)F]FEDAA1106 was 370
      740GBq/MUmol and 37-222GBq/MUmol at EOB, respectively.

PMID- 22469869
TI  - IKK NBD peptide inhibits LPS induced pulmonary inflammation and alters
      sphingolipid metabolism in a murine model.
AB  - Airway epithelial NF-kappaB is a key regulator of host defence in bacterial
      infections and has recently evolved as a target for therapeutical approaches.
      Evidence is accumulating that ceramide, generated by acid sphingomyelinase
      (aSMase), and sphingosine-1-phosphate (S1-P) are important mediators in host
      defence as well as in pathologic processes of acute lung injury. Little is known
      about the regulatory mechanisms of pulmonary sphingolipid metabolism in bacterial
      infections of the lung. The objective of this study was to evaluate the influence
      of NF-kappaB on sphingolipid metabolism in Pseudomonas aeruginosa LPS-induced
      pulmonary inflammation. In a murine acute lung injury model with intranasal
      Pseudomonas aeruginosa LPS we investigated TNF-alpha, KC (murine IL-8), IL-6, MCP
      1 and neutrophilic infiltration next to aSMase activity and ceramide and S1-P
      lung tissue concentrations. Airway epithelial NF-kappaB was inhibited by
      topically applied IKK NBD, a cell penetrating NEMO binding peptide. This
      treatment resulted in significantly reduced inflammation and suppression of
      aSMase activity along with decreased ceramide and S1-P tissue concentrations down
      to levels observed in healthy animals. In conclusion our results confirm that
      changes in sphingolipid metabolim due to Pseudomonas aeruginosa LPS inhalation
      are regulated by NF-kappaB translocation. This confirms the critical role of
      airway epithelial NF-kappaB pathway for the inflammatory response to bacterial
      pathogens and underlines the impact of sphingolipids in inflammatory host defence
      mechanisms.

PMID- 22469870
TI  - AgGaSe2 thin films grown by chemical close-spaced vapor transport for
      photovoltaic applications: structural, compositional and optical properties.
AB  - Thin films of chalcopyrite AgGaSe(2) have been successfully grown on glass and
      glass/molybdenum substrates using the technique of chemical close-spaced vapor
      transport. The high crystallinity of the samples is confirmed by grazing
      incidence x-ray diffraction, scanning and transmission electron microscopy, and
      optical transmission/reflection spectroscopy. Here, two of the three expected
      direct optical bandgaps are found at 1.77(2) and 1.88(6) eV at 300 K. The lowest
      bandgap energy at 4 K is estimated to be 1.82(3) eV. Photoluminescence
      spectroscopy has further revealed the nature of the point defects within the
      AgGaSe(2), showing evidence for the existence of very shallow acceptor levels of
      5(1) and 10(1) meV, and thus suggesting the AgGaSe(2) phase itself to exhibit a p
      type conductivity. At the same time, electrical characterization by Hall, Seebeck
      and four-point-probe measurements indicate properties of a compensated
      semiconductor. The electrical properties of the investigated thin films are
      mainly influenced by the presence of Ag(2)Se and Ga(2)O(3) nanometer-scaled
      surface layers, as well as by Ag(2)Se inclusions in the bulk and Ag clusters at
      the layers' rear side.

PMID- 22469871
TI  - Long-term storage and impedance-based water toxicity testing capabilities of
      fluidic biochips seeded with RTgill-W1 cells.
AB  - Rainbow trout gill epithelial cells (RTgill-W1) are used in a cell-based
      biosensor that can respond within one hour to toxic chemicals that have the
      potential to contaminate drinking water supplies. RTgill-W1 cells seeded on
      enclosed fluidic biochips and monitored using electric cell-substrate impedance
      sensing (ECIS) technology responded to 18 out of the 18 toxic chemicals tested
      within one hour of exposure. Nine of these chemical responses were within
      established concentration ranges specified by the U.S. Army for comparison of
      toxicity sensors for field application. The RTgill-W1 cells remain viable on the
      biochips at ambient carbon dioxide levels at 6 degrees C for 78weeks without
      media changes. RTgill-W1 biochips stored in this manner were challenged with
      9.4MUM sodium pentachlorophenate (PCP), a benchmark toxicant, and impedance
      responses were significant (p<0.001) for all storage times tested. This
      poikilothermic cell line has toxicant sensitivity comparable to a mammalian cell
      line (bovine lung microvessel endothelial cells (BLMVECs)) that was tested on
      fluidic biochips with the same chemicals. In order to remain viable, the BLMVEC
      biochips required media replenishments 3 times per week while being maintained at
      37 degrees C. The ability of RTgill-W1 biochips to maintain monolayer integrity
      without media replenishments for 78weeks, combined with their chemical
      sensitivity and rapid response time, make them excellent candidates for use in
      low cost, maintenance-free field-portable biosensors.

PMID- 22469872
TI  - Patient registry of outcomes in spasticity care.
AB  - OBJECTIVE: This study aimed to provide clinical injection data and real-world
      patient-reported and clinical outcomes for the chemodenervation and neurolytic
      treatment of muscle overactivity including spasticity in patients with traumatic
      brain injury and stroke. DESIGN: This study used a prospective multicenter
      observational design. The participants were 487 patients with stroke or traumatic
      brain injury. The interventions used were onabotulinumtoxin A or phenol. Nine
      subjects received both onabotulinumtoxin A and phenol. The main outcome measures
      were satisfaction and goal attainment, pain, and Ashworth Scale scores. RESULTS:
      The most commonly treated pattern of dysfunction in the upper limb was the flexed
      wrist, with the flexor carpi radialis as the most frequently treated muscle. The
      mean total dose for the upper limb muscle was 57.7 +/- 34.1 U, and phenol volume
      was 3.9 +/- 0.7 ml. The most commonly treated pattern of dysfunction in the lower
      limb was the equinovarus/equinus foot, with the medial/lateral gastrocnemius as
      the most frequently treated muscles. The mean total dose for the lower limb
      muscle was 93.8 +/- 63.5 U, and phenol volume was 4.1 +/- 1.3 ml. There was a
      significant improvement in Ashworth Scale and pain scores. Generally, the
      patients reported that they were satisfied with their treatment and made progress
      toward their goals. No significant treatment-related adverse effects were
      reported. CONCLUSIONS: Based on 487 patients with stroke and traumatic brain
      injury who were selected by their physician and clinical presentation for
      treatment using chemodenervation and neurolysis, this report of injection data
      reflecting actual clinical practice may serve as a further clinical guide in the
      management of patients with muscle overactivity, including spasticity.

PMID- 22469873
TI  - Vital capacity in spinal muscular atrophy.
AB  - OBJECTIVE: This work describes and correlates plateau/maximum observed vital
      capacity (VC) with spinal muscular atrophy (SMA) severity and prognosis for
      autonomous breathing. DESIGN: SMA severity was correlated with VC, onset,
      paradoxical breathing, age at definitive dependence on continuous mechanical
      ventilation (DDCV), and age at first respiratory hospitalization and gastrostomy.
      RESULTS: Ten severe SMA 1A patients with DDCV before 6 mos of age had maximum
      observed and plateau VC of 100 ml or less, with plateaus for six at 10.3 (range,
      3-48) mos. Another 120 had typical SMA 1B defined by any three of the following:
      acute respiratory failure before 12 mos of age, gastrostomy before 12 mos of age,
      DDCV before 10 yrs of age, and VC not exceeding 200 ml, with plateaus for 15 at
      26.4 (6-138) mos. Fifteen were with mild type 1C defined by three of the
      following: VC exceeding 200 ml, acute respiratory failure after 1 yr of age,
      gastrostomy after 1 yr of age, and no DDCV before 10 yrs of age and had a
      plateau/maximum observed mean VC of 409 (range, 200-1175) ml at 8.9 (range, 7-10)
      yrs of age. Of 88 patients with SMA 2 and paradoxical breathing (2A), 16 had a
      mean plateau/maximum observed VC of 758 (range, 460-2100) ml. DDCV with no
      autonomous breathing always followed plateauing of VC. Types 2B, 3, and 4
      patients attained normal VC. Intergroup VC differences were significant (P <
      0.05) for 1A, 1B, 1C, 2A, and 2B-4. When intubated and "unweanable," 50-ml VC
      signaled the ability for autonomous breathing 1 to 21 days after extubation.
      CONCLUSIONS: VC should be monitored from birth. It correlates with prognosis with
      SMA 1A VCs not exceeding 100 ml or 1B 200 ml. Patients who attained 200 ml at any
      time (milder 1C) retain some ability to breathe after 10 yrs of age.

PMID- 22469874
TI  - Acute stroke phase voluntary cough and correlation with maximum phonation time.
AB  - OBJECTIVE: This study aimed to assess cough effectiveness after a stroke and to
      propose a bedside screening test. DESIGN: Patients who had had ischemic
      hemispheric stroke were recruited and followed up for 2 mos. Maximum phonation
      time (MPT) was assessed during the first 10 days. Aspiration was evaluated on
      days 2 and 10 after stroke. Lung function testing was performed on day 10. Peak
      cough flow less than 160 liters/min was defined as the criterion for cough
      ineffectiveness. Correlation between peak cough flow and MPT was determined, and
      the optimal cutoff value relating MPT to effective cough was determined using
      receiver operating characteristic analysis when referring to peak cough flow.
      RESULTS: Of the 70 patients, 6 developed pneumonia (mean time, 1.7 +/- 2.4 days).
      Lung function assessment in 32 cases revealed general reduced cough
      effectiveness. MPT was correlated with peak cough flow (r = 0.413, P = 0.025),
      and an MPT cutoff of 10 secs was identified. Forty-seven patients were able to
      perform MPT on day 2; 49 were able to perform on day 10. Patients with MPT of 10
      secs or longer had less frequent aspiration on both day 2 (5.9% vs. 36.7%, P =
      0.034) and day 10 (2.9% vs. 26.6%, P = 0.026). CONCLUSIONS: Cough effectiveness
      was reduced at the time of greatest risk for pneumonia. MPT provides a reliable
      bedside screening test of cough effectiveness.

PMID- 22469875
TI  - Development of an objective test of upper-limb function in tetraplegia: the
      capabilities of upper extremity test.
AB  - OBJECTIVE: This study aimed to describe the development, internal consistency,
      and validity of the Capabilities of Upper Extremity Test (CUE-T) for persons with
      tetraplegia. DESIGN: This study used a cross-sectional sample of adults with
      spinal cord injury. CUE-T items and procedures were developed based on the CUE
      Questionnaire. Thirty adults with complete and incomplete spinal cord injury,
      neurologic levels C4-T6, were tested on one occasion. Each received upper limb
      manual muscle testing and the CUE Questionnaire followed by the CUE-T. Raw item
      scores were converted to a 0-4 scale. Internal consistency was evaluated using
      Cronbach alpha. Item score distributions were evaluated for ceiling and floor
      effects. Spearman correlations of total, right, and left CUE-T scores with upper
      limb motor scores and international hand classification were performed. RESULTS:
      There were 23 men and 7 women, with an average age of 44.8 yrs. Twenty subjects
      had motor complete injuries; 13 had motor levels C4-C6, 13 had between C7 and C8,
      and 4 were T1 or below. The Cronbach alpha for the CUE-T was 0.96. Item score
      distributions found ceiling effects for the push/pull items, suggesting that
      these items were too easy. Correlations of right- and left-sided scores with
      upper-limb motor scores and international hand classification were strong, with
      all values greater than or equal to 0.89. CONCLUSIONS: The CUE-T displays good
      internal consistency and excellent construct validity on preliminary testing.
      Push/pull tests should be revised to increase difficulty. Reliability and
      responsiveness should be determined.

PMID- 22469876
TI  - Influence of weight classification on children stepping over obstacles.
AB  - The objective of this study was to evaluate how weight classification relates to
      meeting task constraints. Using a cross-sectional design, three-dimensional
      motion data were collected while children crossed obstacles of various heights.
      Twelve normal-weight (>=5th and <85th percentile on growth charts) and 12
      overweight or obese (>=85th percentile on growth charts) 4- to 13-yr-olds
      participated. During obstacle crossing, children who were overweight or obese
      took longer to reach maximum knee height and to achieve foot contact (all P =
      0.04). Normal-weight children landed flat-footed after obstacle crossing whereas
      overweight and obese children landed heel first (P = 0.04). Children had higher
      coefficients of variation for ankle position at heel contact after crossing
      medium obstacles (P = 0.02). Slower rates of obstacle crossing and landing heel
      first after crossing obstacles could be behind higher risks of falls for children
      who are overweight or obese.

PMID- 22469877
TI  - The mirror therapy program enhances upper-limb motor recovery and motor function
      in acute stroke patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of the mirror
      therapy program on upper-limb motor recovery and motor function in patients with
      acute stroke. DESIGN: Twenty-six patients who had an acute stroke within 6 mos of
      study commencement were assigned to the experimental group (n = 13) or the
      control group (n = 13). Both experimental and control group members participated
      in a standard rehabilitation program, but only the experimental group members
      additionally participated in mirror therapy program, for 25 mins twice a day,
      five times a week, for 4 wks. The Fugl-Meyer Assessment, Brunnstrom motor
      recovery stage, and Manual Function Test were used to assess changes in upper
      limb motor recovery and motor function after intervention. RESULTS: In upper-limb
      motor recovery, the scores of Fugl-Meyer Assessment (by shoulder/elbow/forearm
      items, 9.54 vs. 4.61; wrist items, 2.76 vs. 1.07; hand items, 4.43 vs. 1.46,
      respectively) and Brunnstrom stages for upper limb and hand (by 1.77 vs. 0.69 and
      1.92 vs. 0.50, respectively) were improved more in the experimental group than in
      the control group (P < 0.05). In upper-limb motor function, the Manual Function
      Test score (by shoulder item, 5.00 vs. 2.23; hand item, 5.07 vs. 0.46,
      respectively) was significantly increased in the experimental group compared with
      the control group (P < 0.01). No significant differences were found between the
      groups for the coordination items in Fugl-Meyer Assessment. CONCLUSIONS: This
      study confirms that mirror therapy program is an effective intervention for upper
      limb motor recovery and motor function improvement in acute stroke patients.
      Additional research on mirror therapy program components, intensity, application
      time, and duration could result in it being used as a standardized form of hand
      rehabilitation in clinics and homes.

PMID- 22469878
TI  - Designing the objective structured clinical examination to cover all major areas
      of physical medicine and rehabilitation over 3 yrs.
AB  - The Accreditation Council for Graduate Medical Education requires that training
      programs comprehensively evaluate residents in the six core Accreditation Council
      for Graduate Medical Education competencies. One of the ways we do this in our
      residency is by administering a nine-station Objective Structured Clinical
      Examination (OSCE) at the end of each year, which evaluates tasks such as history
      taking, focused physical examination, communication, professionalism, procedural
      skills, management, prescription writing, and understanding systems-based
      practice. We have classified our OSCE stations into what we consider key areas in
      our field and assessed these on a rotating basis over 3 yrs. This results in the
      assessment of 27 areas over the 3 yrs of residency. Structuring the OSCE as a
      series of stations over 3 yrs is an efficient method to evaluate residents'
      competencies that are required by the Accreditation Council for Graduate Medical
      Education and certifying boards. An analysis of OSCE scores when compared with
      American Board of Physical Medicine & Rehabilitation parts 1 and 2 scores and
      final summative resident evaluation scores reveals that OSCE results correlate
      with part 1 scores and final evaluation scores but do not show the same strong
      correlations with part 2 scores. We discuss the way the OSCE can complete other
      assessment techniques and ways to improve cases in the future.

PMID- 22469879
TI  - Multilevel thoracic disk herniations in a young woman.

PMID- 22469880
TI  - Effects of exercise training and detraining in patients with fibromyalgia
      syndrome: a 3-yr longitudinal study.
AB  - OBJECTIVE: This study aimed to evaluate the immediate effects of a 6-mo combined
      exercise program on quality-of-life, physical function, depression, and aerobic
      capacity in women with fibromyalgia syndrome and to determine the impact of
      repeated delivery of the intervention. DESIGN: Forty-one women with fibromyalgia
      were randomly assigned to a training group (EG; n = 21) and a control group (CG;
      n = 20). Quality-of-life and physical function were assessed using the 36-item
      Short-Form Health Survey (SF-36) and the Fibromyalgia Impact Questionnaire, and
      depression was measured using the Beck Depression Inventory. Physical fitness was
      measured using the 6-min Walk Test. Outcomes were assessed at baseline and after
      each 6-mo intervention, which was delivered over 30 mos (6 mos of training and 6
      mos of detraining). RESULTS: After a 6-mo combined exercise program, there was a
      significant improvement in the Fibromyalgia Impact Questionnaire (P < 0.0005) for
      the training group over the control group. Repeated-measures analysis of variance
      across all time points demonstrated significant main effects for time for the
      Fibromyalgia Impact Questionnaire, SF-36, Beck Depression Inventory and the 6-min
      Walk Test, but there were no between-group interaction effects. For the EG, there
      were significant within-group changes in the Fibromyalgia Impact Questionnaire,
      SF-36, and Beck Depression Inventory at the final time point; however, there were
      no within-group changes for the control group. Improvement achieved for the
      training group were maintained during the detraining period. CONCLUSIONS: A long
      term exercise program can produce immediate improvements in key health domains in
      women with fibromyalgia. The benefits achieved with regular training can be
      maintained for 30 mos. The lack of difference between groups over time may be
      caused by attrition and consequent lack of power at the final time point.

PMID- 22469881
TI  - Dual inhibition of sphingosine kinase isoforms ablates TNF-induced drug
      resistance.
AB  - Recent research has demonstrated that aberrant sphingolipid signaling is an
      important mechanism of chemoresistance in solid tumors. Sphingosine kinase
      (Sphk), the primary enzyme metabolizing the sphingolipid ceramide into
      sphingosine-1-phosphate (S1P), is a primary mediator of breast cancer promotion,
      survival and chemoresistance. However, to date the mechanism of Sphk-mediated
      drug resistance is poorly understood. Using the dual sphingosine kinase isozyme
      inhibitor, SKI-II (4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol), we explored
      the effects of sphingosine kinase inhibition on multi-drug-resistant breast
      cancer cells. We demonstrate that SKI-II alters endogenous sphingolipid signaling
      and decreases cancer proliferation, survival and viability. Furthermore,
      pharmacological inhibition of Sphk1/2 induced intrinsic apoptosis in these cells
      through modulation of the NF-kappaB pathway. SKI-II decreases NF-kappaB
      transcriptional activity through altered phosphorylation of the p65 subunit.
      Taken together, these results suggest that Sphk may be a promising therapeutic
      target in chemoresistant cancers.

PMID- 22469882
TI  - Graft-versus-host disease-related cytokine-driven apoptosis depends on p73 in
      cytokeratin 15-positive target cells.
AB  - Acute graft-versus-host disease (GVHD), a major complication of allogeneic stem
      cell transplantation, involves cytotoxic soluble and cellular effectors that
      selectively induce apoptosis in normally apoptosis-resistant, cytokeratin 15
      (K15)-expressing epithelial stem cells residing at the tips of rete ridges of
      human epidermis and in analogous rete-like prominences (RLPs) of murine dorsal
      lingual epithelium. The mechanisms whereby epithelial stem cells are rendered
      vulnerable to apoptosis during allostimulation are unknown. We hypothesized that
      GVHD-induced target cell injury may be related to pathways involving the p53
      family that are constitutively expressed by epithelial stem cells and designed to
      trigger physiological apoptosis as a result of environmental danger signals.
      Among the p53 family members, we found that p73 protein and mRNA were
      preferentially expressed in K15(+) RLPs of murine lingual squamous epithelium. On
      in vitro exposure to recombinant TNF-alpha and IL-1 in an organ culture model
      previously shown to replicate early GVHD-like target cell injury, apoptosis was
      selectively induced in K15(+) stem cell regions and was associated with induction
      of phosphorylated p73, a marker for p73 activation, and apoptosis was abrogated
      in target tissue obtained from p73-deficient (p73(-/-)) mice. Evaluation of early
      in vivo lesions in experimental murine GVHD disclosed identical patterns of
      phosphorylated p73 expression that coincided with the onset of effector T cell
      infiltration and target cell apoptosis within K15(+) RLPs. This study is the
      first to suggest that paradoxical apoptosis in GVHD of physiologically protected
      K15(+) epithelial stem cells is explainable, at least in part, by cytokine
      induced activation of suicide pathways designed to eliminate stem cells after
      exposure to deleterious factors perceived to be harmful to the host.

PMID- 22469883
TI  - TNF-inhibition with etanercept for graft-versus-host disease prevention in high
      risk HCT: lower TNFR1 levels correlate with better outcomes.
AB  - Graft-versus-host disease (GVHD) causes most non-relapse mortality (NRM) after
      alternative donor (unrelated and mismatched related) hematopoietic cell
      transplant (HCT). We previously showed that increases in day +7 TNF-receptor-1
      (TNFR1) ratios (posttransplantation day +7/pretransplantation baseline) after
      myeloablative HCT correlate with outcomes including GVHD, NRM, and survival.
      Therefore, we conducted a phase II trial at 2 centers, testing whether the
      addition of the TNF-inhibitor etanercept (25 mg twice weekly from start of
      conditioning to day +56) to standard GVHD prophylaxis would lower TNFR1 levels,
      reduce GVHD rates, and improve NRM and survival. Patients underwent myeloablative
      HCT from a matched unrelated donor (URD; N = 71), 1-antigen mismatched URD (N =
      26), or 1-antigen mismatched related donor (N = 3) using either total body
      irradiation (TBI)-based conditioning (N = 29) or non-TBI-based conditioning (N =
      71). Compared to historical controls, the increase in posttransplantation day +7
      TNFR1 ratios was not altered in patients who received TBI-based conditioning, but
      was 40% lower in patients receiving non-TBI-based conditioning. The latter group
      experienced relatively low rates of severe grade 3 to 4 GVHD (14%), 1-year NRM
      (16%), and high 1-year survival (69%). These findings suggest that (1) the
      effectiveness of TNF-inhibition with etanercept may depend on the conditioning
      regimen, and (2) attenuating the expected rise in TNFR1 levels early
      posttransplantation correlates with good outcomes.

PMID- 22469884
TI  - Multicenter, randomized, open-label study comparing the efficacy and safety of
      micafungin versus itraconazole for prophylaxis of invasive fungal infections in
      patients undergoing hematopoietic stem cell transplant.
AB  - This multicenter, randomized, open-label phase III study compared the efficacy
      and safety of micafungin and itraconazole in prophylaxis of invasive fungal
      infections in neutropenic patients undergoing hematopoietic stem cell transplants
      in China. Micafungin (50 mg/day i.v.) or itraconazole (5 mg/kg/day p.o.) was
      administered for <=42 days. The primary endpoint, treatment success, was defined
      as no proven, probable, or suspected invasive fungal infection through therapy
      and the absence of proven or probable invasive fungal infection through the end
      of 4 weeks after therapy. Noninferiority of micafungin against itraconazole was
      established if the lower boundary of the 95% confidence interval (CI) was >10%.
      Of 287 patients, 283 were evaluable for efficacy (136 for micafungin, 147 for
      itraconazole, intent-to-treat population). Treatment success was documented in
      92.6% (126 of 136) of micafungin-treated patients and 94.6% (139 of 147) of
      itraconazole-treated patients (95% CI, -7.562% to 3.482%; P = .48), indicating
      noninferiority of micafungin against itraconazole. Results were similar for
      patients treated per protocol. Whereas the rates of proven or probable invasive
      fungal infection were numerically higher with micafungin than itraconazole at
      4.4% (6 of 136) and 1.4% (2 of 147), rates of suspected invasive fungal infection
      were similar at 5.9% (8 of 136) and 7.5% (11 of 147), respectively. More patients
      treated with micafungin than itraconazole completed the study (82.9% versus
      67.3%, respectively). Significant differences in incidence of withdrawal due to
      an adverse event (4.4% versus 21.1%) and drug-related adverse events (8% versus
      26.5%) were shown between micafungin and itraconazole (P = .00, chi-square test).
      Micafungin was as effective as itraconazole in preventing invasive fungal
      infections in patients with neutropenia. In comparison to itraconazole, treatment
      tolerance was much better with micafungin.

PMID- 22469885
TI  - An approximate reconstruction method for helical cone-beam differential phase
      contrast computed tomography images.
AB  - Differential phase-contrast computed tomography (DPC-CT) is a novel x-ray
      inspection method. Currently, DPC-CT reconstruction problems are solved by using
      parallel-beam, fan-beam and cone-beam algorithms. The above algorithms cannot
      show the internal structures of rod-shaped objects well enough for only
      reconstructing a few slices. The helical cone-beam algorithms have significant
      advantages for rod-shaped objects over other algorithms. Along with our numerical
      evaluation and verification, we report a PI-line-based approximate algorithm for
      helical cone-beam DPC-CT, which can be applied to reconstruct the refractive
      index decrement distribution of the samples directly from phase-contrast
      projection images. Simulations using a 3D Shepp-Logan phantom are carried out to
      verify the proposed algorithm. Reconstruction results show that the proposed
      algorithm can provide higher quality performance compared with the existing
      interpolation-based reconstruction algorithm.

PMID- 22469886
TI  - [Community health care trends for the coming decade: advantages and opportunities
      for nurses].
AB  - Health policies in many advanced countries have been revised and reformed to
      address increasing public healthcare demands and increasingly limited resources.
      Upgrading the quality and quantity of community healthcare is the most effective
      solution. Implementation of the National Health Insurance system in Taiwan has
      introduced instability into the medical system, as insurance premiums no longer
      correspond to healthcare demand, Taiwanese live inadequately healthy lifestyles,
      and expectations of the healthcare system continue to grow. Community nursing now
      faces many challenges at this historic crossroads. This paper tries to analyze
      factors in the domestic and international environment that affect Taiwan's
      national community healthcare. These include changes in population structure,
      adjustment of governmental policies, the implementation of nursing and medical
      regulations, and consensus among nursing professional groups. The authors hope to
      anticipate the trends and prospects and advantages and opportunities in community
      healthcare in the coming decade in order to help our community healthcare
      partners prepare a good foundation and establish a model for the national
      healthcare system and nursing profession.

PMID- 22469887
TI  - [Development trends and future challenges in community nurse practitioner].
AB  - Community health nursing is an innovative aspect of healthcare that has grown in
      response to changing environmental and social structure changes into a worldwide
      movement. Taiwan's fast growing elderly population, improving health technologies
      and rising healthcare costs impact significantly upon the development and
      definition of the scope of practice for community health nurse nurses. This paper
      explores the innovative community care model development experiences of several
      countries and reviews the scope of practice of community health nurse
      practitioners in each. We further explore the current situation of nurse
      practitioners in Taiwan and suggest a future path for Taiwan community health
      nurse practitioners development and policymaking.

PMID- 22469888
TI  - [Comprehensive cross-cultural care: an exploration of the immigrant care barriers
      and cross-cultural care competency of community nurses].
AB  - Advanced information technologies and increasingly convenient transportation
      links have drawn countries forward into the current era of globalization, while
      growing transnational migration has encouraged multicultural trends. The
      difficulties new immigrants have in adapting to their adopted culture is an issue
      to which healthcare must be sensitive and responsive. Information on approaches
      to cross-cultural healthcare is sparse in the Taiwan literature. In this paper,
      the author reviews relevant domestic and overseas articles to assess historical
      and government policy trends as well as cross-cultural care competency
      development. As different ethnic populations increase, each should be provided
      with proper health education supported by medical volunteers from their own
      ethnicities. In terms of policy, healthcare personnel should understand their own
      culture and develop sensitivity to the needs and concerns of others. As part of
      their training, healthcare staff should gain a second language competency in
      order to enhance cultural literacy and enhance cross-cultural sensitivity and
      overall sensitivity within the healthcare system to the needs of the global
      community.

PMID- 22469889
TI  - [Steadfast and dependable: trans-cultural community healthcare in Taiwan].
AB  - Taiwan's multicultural population requires that nursing educators address and
      effectively manage trans-cultural healthcare issues. A longstanding lack of self
      reflection on cultural issues has caused a gap between community nursing and the
      health needs of Taiwan's indigenous people. Taiwan's newer immigrant populations
      from Southeast Asia, Mainland China and elsewhere have added further cultural
      complexity to Taiwan's community healthcare landscape. In this paper, the authors
      apply their practical experience in community nursing to derive the special
      healthcare needs of indigenous and new immigrant populations based on the unique
      cultural attributes and health concepts of these populations. We hope to help
      nursing staff develop cultural self-awareness and sensitivity by admiring,
      respecting, and learning from their own culture while empathizing with and
      appreciating the cultures of their healthcare clients. By doing so, healthcare
      providers can further examine the cultural characteristics of the professional
      nursing system and conduct trans-cultural evaluations.

PMID- 22469890
TI  - [Violent schizophrenia patients: caregiver burden and related factors].
AB  - BACKGROUND: Schizophrenia-related violent behavior is a social stigma borne by
      schizophrenic patients and a highly painful burden faced by caregivers. PURPOSE:
      This study focused on how primary caregivers deal with schizophrenic patient
      violent behavior and factors that affect this burden. METHODS: Researchers
      recruited a purposive sample from the acute wards of a psychiatric hospital in
      Taipei city. This cross-sectional study studied 100 primary caregivers of
      schizophrenic patients with a history of violent behavior. Socio-demographic data
      were collected using structured questionnaires on coping methods and caregiver
      burden. RESULTS: Results found an average primary caregiver burden score of 30.8
      points, indicating a moderate degree of burden. Factors contributing to the total
      care burden were: patient occupation, caregiver level of education, emotional
      coping method, negative cognitive coping method and violent behavior type. After
      multiple regression analysis, the two significant factors affecting caregiver
      burden were identified as: Emotional coping method and violent behavior type.
      CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study highlighted a higher burden
      in violent schizophrenic patient caregivers who use emotional coping methods.
      Researchers recommended that clinical staff voluntarily assess caregiver burdens
      and methods of coping with patients' violent behavior in order to help caregivers
      develop specific and efficient coping strategies to reduce care burden.

PMID- 22469891
TI  - [Depressive symptoms in people living with HIV: related factors].
AB  - BACKGROUND: People living with HIV (human immunodeficiency virus) are at a high
      risk of depressive symptoms attributed to disease progression and HIV-related
      stress. While depressive symptoms are difficult to detect, in HIV patients they
      may negatively impact upon quality of life, decrease adherence to antiretroviral
      therapies, and further exacerbate disease progression. PURPOSE: Study purposes
      were to: (1) explore relationships among immune function indicators, perceived
      stress, social stigma and depressive symptoms and (2) identify depressive symptom
      indicators in HIV patients. METHODS: Researchers recruited a total of 160
      participants from infectious disease outpatient clinics at a university hospital
      in southern Taiwan. Chart reviews and four self-administered questionnaires (Beck
      Depression Inventory-II (BDI-II), Perceived Stress Scale, Multidimensional Scale
      of Perceived Social Support, and Social Impact Scale) were used to collect data.
      RESULTS: Symptoms of depression (BDI >= 14) were observed in 68 (42.5%) patients
      and symptoms of major depression (BDI >= 29) in 25 (15.6%). We found immune
      function indicators negatively associated with depressive symptoms (p < .05) and
      perceived stress and social stigma positively associated with depressive symptoms
      (p < .01). Stepwise multiple regression analysis indicated that perceived stress
      and social stigma accounted for 44.4% of depressive symptom variance. CONCLUSION:
      Findings suggest that reducing perceived stress and social stigma may positively
      affect perceived depressive symptoms in this population and may be referenced in
      future development of related interventions.

PMID- 22469892
TI  - [Relationships among job rotation perception and intention, job satisfaction and
      job performance: a study of Tainan area nurses].
AB  - BACKGROUND: There have been major changes to the medical care system and
      heightened standards for quality in the nursing profession in recent decades.
      Multifunctional capabilities are closely related to individual working attitudes,
      and work satisfaction directly affects group performance. Hospital administrators
      increasingly expect to utilize nursing staffs flexibly in terms of working hours
      and shift rotation assignments. This study addresses the need to provide
      appropriate educational training to nurses and effectively delegate and utilize
      human resources in order to help nurses adapt to the rapidly changing medical
      environment. PURPOSE: This study on nursing staff in Tainan area explored the
      relationships between job rotation, work performance and satisfaction. METHODS:
      We used a questionnaire sampling method to survey nurses working in the Tainan
      area of southern Taiwan. Subjects were volunteers and a total 228 valid
      questionnaires (99.13%) were returned out of a total 230 sent. RESULTS: Both job
      satisfaction and performance correlated positively with job rotation perception
      and intention; Job satisfaction and job performance were positively related; Job
      satisfaction was found to affect work performance via job rotation perception and
      intention. CONCLUSIONS: This study found the hospital nursing staff rotation plan
      to be an effective management method that facilitates social evolution to
      increase positive perceptions of work rotation. Nursing staffs thus become more
      accepting of new positions that may enhance job satisfaction.

PMID- 22469893
TI  - [Factors associated with non-utilization of mammographic screening services in
      middle-aged and elderly women in Taiwan].
AB  - BACKGROUND: Breast cancer is currently the type of cancer with the highest annual
      incidence among women in Taiwan, resulting in a median age of death of 57 years.
      Nevertheless, the proportion of Taiwanese women with a history of mammographic
      screening is relatively low. The international literature associates
      participation in mammographic screening with factors such as age, education
      level, ethnicity, and previous cancer history. Few such studies in Taiwan have
      addressed a cross-section sample that is representative of the overall
      population. PURPOSE: The present study investigated factors associated with non
      utilization of mammographic screening in women aged between 50 to 69 years in
      Taiwan. METHODS: This study used secondary data analysis to investigate data
      obtained from the 2005 National Health Interview Survey in Taiwan. Researchers
      used logistic regression analysis to evaluate factors associated with
      mammographic screening in Taiwanese women based on the Andersen behavioral model
      of health services use. RESULTS: Only 24.3% of the survey population had received
      mammographic screening. Results of multiple logistic regression analysis
      indicated non-utilization of mammographic screening is associated with a
      relatively low education level, being currently employed, a relatively low
      average monthly salary, having no additional insurance coverage outside the
      National Health Insurance, having no physical examination history, and having no
      history of menopausal hormone replacement therapy use. CONCLUSIONS: Hospitals and
      health units may use findings from the present study to plan mammographic
      screening programs. Mammography promotional material should consider the needs of
      women with lower education levels; screening schedules should be coordinated with
      employers and made convenient for working women; and promotional materials should
      target women who have never previously received a physical examination. Enhancing
      the willingness of women to obtain mammography may reduce the threat of breast
      cancer to the lives of Taiwanese women.

PMID- 22469894
TI  - [Reducing blood preparation for total knee arthroplasty: a practical approach].
AB  - BACKGROUND & PROBLEMS: The rate of allogenic blood preparation for an elective
      total knee arthroplasty (TKA) has been as high as 100% at our institute. However,
      most (76.2%) of these preparations were wasted. PURPOSE: This project worked to
      reduce unnecessary blood preparations for this elective procedure and reduce
      resource expenditures. RESOLUTIONS: Key issues identified as requiring resolution
      included: Uncertainty regarding urgent transfusion need, insufficient
      preoperative evaluation of high risk patients, and the use of outdated clinical
      pathways. Measures taken to overcome these issues included redefining transfusion
      triggers using relevant empirical data as conclusive evidence and building a
      general consensus within the medical team while acquiring practical support from
      decision makers. A more comprehensive assessment process for identifying risk
      factors was developed by reviewing and assessing the prior experiences of
      inpatients; New standard procedures for blood preparation and transfusion were
      issued; and related clinical pathways were updated with supplementary measures.
      RESULTS: After project implementation, the blood preparation rate declined
      significantly from 100% to 10.2%. The rate of effective transfusion rate rose
      from 23.8% to 76.2%. CONCLUSIONS: This project combined various medical
      professions to propose practical improvements that effectively access peer
      support. We recommend applying this model in all care units to ensure patient
      safety and lower medical costs while developing a more effective policy for blood
      transfusion.

PMID- 22469895
TI  - [Promoting complete and thorough nurse shift-change reporting in a postoperative
      recovery room].
AB  - BACKGROUND & PROBLEMS: Detailed descriptions of nursing shift tasks are necessary
      to achieve comprehensive nursing care. The 22 cases of postoperative recovery
      ward error reported by our unit included chest tube obstructions, lost dentures
      and other nursing issues. To improve patient health and nurse shift quality, our
      unit established an ad hoc group to collect data helpful to overcoming problems
      attributable to nurse shift changes. We aimed to better nursing care by
      facilitating individualized patient care and avoiding accidents detrimental to
      patient safety. PURPOSE: This project was designed to raise the rate of 100%
      completion of nursing shift-change tasks to 91% of postoperative recovery room
      nurses. RESOLUTION: Newly revised operating standards regarding the recovery
      period after anesthesia established guidelines for a regular audit mechanism and
      in-service education programs for recovery room shift tasks. RESULT: Full
      completion of shift tasks in the postoperative recovery room improved from 73.5%
      to 98.6% of nurses. CONCLUSION: Comprehensive completion of postoperative nursing
      shift-change tasks increases communication between team members, provides
      continuous care for patients, and enhances overall nursing care quality.

PMID- 22469896
TI  - [Elder resilience: a concept analysis].
AB  - Resilience as a social culture adaptation skill is a concept created by a
      combination of culture-based protection and risk factors influenced by
      individual, family and society variables. When encountering life event stresses,
      elder resilience helps the elderly achieve positive adaptation processes and
      results using personal character and support systems. This study used concept
      analysis strategies (Walker & Avant, 2005) to define the concept of elder
      resilience and typical, borderline and contradictory models to define the
      attributes of self-efficacy, hope and expectation, flexibility, sense of humor,
      and positive relationships / social support. We identified antecedent and
      consequence factors of elder resilience and evaluated three empirical measurement
      tools. Concept analysis results are hoped to benefit clinical practice and
      further research. Healthcare provider should further develop a positive
      healthcare philosophy and intervention approaches in order to assist the elderly
      with successful aging and positive adaptation.

PMID- 22469897
TI  - [Medication errors in emergency rooms, intensive care units and pediatric wards].
AB  - Medication safety is a major concern worldwide that directly relates to patient
      care quality and safety. Reducing medication error incidents is a critical
      medication safety issue. This literature review article summarizes medication
      error issues related specifically to three hospital units, namely emergency rooms
      (ERs), intensive care units (ICUs), and pediatric wards. Time constrains, lack of
      patient history details and the frequent need to use rapid response life-saving
      medications are key factors behind high ER medication error rates. Patient hypo
      responsiveness, complex medication administration and frequent need to use high
      alert medications are key factors behind high ICU medication error rates.
      Medication error in pediatric wards are often linked to errors made by nurses in
      calculating dosage based on patient body weight. This article summarizes the
      major types of medication errors reported by these three units in order to
      increase nurse awareness of medication errors and further encourage nurses to
      apply proper standard operational procedures to medication administration.

PMID- 22469898
TI  - [Using ecological systems theory in community health assessment].
AB  - The health of urban community residents is an issue of growing concern due to
      ecological degredation, increasingly extreme changes in weather, the growing
      prevalence of economic downturns, and chronic population structure imbalances
      (e.g., rising elderly and unmarried populations, low birth rates, and rising
      immigrant populations) around the globe. Although the theory of ecology is
      commonly used by domestic and international researchers to explore health
      promotion issues in modern society, it has not been applied in assessing the
      problems of community health in Taiwan or elsewhere. This paper focused on one
      community in Taipei City's Xinyi District to investigate the feasibility of
      applying the ecological system theory to urban community health assessments in
      Taiwan and analyzed the influence of external environments on residents' health.
      Researchers used observation, in-depth interviews, a questionnaire survey and
      literature review to frame research and collect data. Community health assessment
      results show one of the main health problems in the target community resulted
      from inadequate resident abilities and actions related to health promotion. Some
      residents also maintained only distant interpersonal relationships with people in
      their immediate neighborhood. Findings suggest the need for implementing concrete
      schemes based on four ecological systems to resolve identified health problems
      that included inadequate community human resource integration and community
      consensus building.

PMID- 22469899
TI  - [Applying the human dignity ideals of Confucianism and Kant to psychiatric
      nursing: from theory to practice].
AB  - Literature articles and clinical observation suggest disease and environmental
      factors as primary causes of the low self-esteem and stigmatization that typify
      most psychiatric patients. These patients are at risk of injury when subjected to
      inappropriate physical restraint. Hospital staffs, including nurses, are in
      immediate and close contact with psychiatric patients. Mencius's and Kant's
      thoughts on human dignity can enhance reflections on clinical nursing practices.
      Mencius's belief that preserving life is not the most desirable thing and death
      is not the most hated thing can help nurses realize the human dignity of
      psychiatric patients by understanding that, as an unrighteous act is more
      detestable than death, the meaning and value of righteousness are greater than
      life itself. In light of Kant's views on human dignity, nurses should treat
      patients as goals rather than means. Exploring such ideas can raise nursing
      quality, restore a positive sense of humanity to psychiatric patients, and
      develop nursing values and meaning to a higher plane.

PMID- 22469900
TI  - [Applying the synactive theory of development to the care of a premature infant
      with sucking problems].
AB  - Sucking problems in an infant born prematurely at 24 weeks and 5 days were
      identified through systematic behavioral observation and family assessment.
      Reasons underlying the infant's sucking problems included poor sucking and
      swallowing skills due to an immature nervous system, a chaotic care environment
      and ecology, and unimplemented sucking and feeding care procedures. Due to the
      paucity of domestic diagrams related to oral-sucking training for premature
      babies, in addition to reviewing the literature and establishing a sucking
      training program to help the infant establish a regular sucking pattern, we also
      applied the synactive theory of development and improved the hospital feeding
      environment and ecology to reduce environmental factors that could affect sucking
      care such as ambient light and noise and feeding schedules. We observed implied
      infant sucking pattern actions such as restlessness, mouth shakes, and irritation
      and provided the mother with an appropriate feeding schedule. We helped foster
      parent-child attachment and enhanced the mother's post-discharge caring
      confidence. Home visits were also conducted after discharge to assess the home
      care environment and give instant consultation, providing holistic health care
      with sustained quality of care.

PMID- 22469901
TI  - Optimizing insecticide resources: global trends in vector control.

PMID- 22469902
TI  - Optical and electrochemical properties of heteroditopic ion receptors derived
      from crown ether-based calix[4]arene with amido-anthraquinone pendants.
AB  - Two heteroditopic receptors based on a calix[4]arene crown ether containing
      amidoanthraquinone pendants in cone and 1,3-alternate conformations (1 and 2,
      respectively) were synthesized. Photophysical properties of 1 and 2 were studied
      by UV-vis and fluorescence spectrophotometry in dried CH(3)CN. Both 1 and 2
      showed the highest sensitivity towards F(-) through the appearance of a new
      charge transfer band at 500 nm and the enhancement of the emission spectra at
      lambda(em) = 542 nm and 528 nm respectively. Interestingly, in the presence of
      K(+), the fluorescence intensity of 1 at 542 nm increased around 2 fold compared
      to that in the absence of K(+) upon addition of F(-), while this phenomenon was
      not observed in the case of receptor 2. Cyclic voltammograms of receptors 1 and 2
      showed two consecutive one-electron reversible waves in 40% v/v CH(3)CN in
      CH(2)Cl(2), corresponding to two single-electron reductions to give mono- and
      dianions species at E(1/2)I = -1.21 V and E(1/2)II = -1.66 V as well as E(1/2)I =
      -1.25 V and E(1/2)II = -1.71 V, respectively. H(2)PO(4)(-) gave remarkable
      potential shifts (ca. 200 mV) of the second reduction waves (E(1/2)II) of both
      free 1 and 2. In the presence of K(+), only receptor 1 gave remarkable potential
      shifts in its redox wave II upon adding F(-) and AcO(-). Therefore, receptors 1
      and 2 exhibited dual sensing modes by fluorescence spectrophotometry and cyclic
      voltammetry. The topology of ligands also played an important role in cooperative
      binding properties of heteroditopic receptor 1 possessing a closer distance
      between a cation and an anion binding. On the other hand, the two ion binding
      sites of receptor 2 were separated by a longer distance and did not support the
      cooperative binding. This resulted in the abstraction of K(+) from receptor 2
      upon addition of anions.

PMID- 22469907
TI  - Spondyloarthritis: the eyes have it: uveitis in patients with spondyloarthritis.

PMID- 22469908
TI  - Heterogeneity of macrophages in injured trigeminal nerves: cytokine/chemokine
      expressing vs. phagocytic macrophages.
AB  - BACKGROUND: Macrophages are important immune effector cells in both innate and
      adaptive immune responses. Injury to peripheral nerves triggers activation of
      resident macrophages and infiltration of haematogenous macrophages, which they
      play critical roles in Wallerian degeneration and neuropathic pain. As
      macrophages are able to change their phenotypes in response to environment cues,
      we attempt to identify distinct phenotypes of macrophages in injured nerves and
      to understand the potential contribution of each macrophage subpopulation to the
      genesis of neuropathic pain associated with nerve injury. METHODS: Rat mental
      nerves (terminal branches of trigeminal nerve) were loosely ligated. Sensitivity
      to mechanical stimuli at the lower lip area was monitored using calibrated von
      Frey Hairs. We examined the expression pattern of Iba-1, MAC1 and ED1 which allow
      us to reveal the immunophenotypes of macrophages at different time points post
      injury. Functional status of each macrophage subpopulation was further
      investigated by colocalization with cytokines/chemokines, myelin basic protein
      and MHC II antigen, which reflect respectively secretory, phagocytic and antigen
      presentation properties of activated macrophages. RESULTS: Following nerve
      injury, a burst of Iba-1(+) macrophages was found in injured mental nerves. Among
      them, we detected two major immunophenotypes: MAC1(+) cytokines/chemokines
      secreting macrophages and ED1(+) phagocytic macrophages. Small, round shaped
      MAC1(+) macrophages were distributed essentially around the lesion site and
      existed only at early time points. Large, irregular and foamy ED1(+) macrophages
      were found among damaged nerve fibers and they persisted for at least 3 months
      post-injury. Although ED1(+) macrophages did not secrete inflammatory mediators,
      they were able to express neurotransmitter CGRP and MHC II at later time points.
      In parallel, we observed that mechanical allodynia developed after the nerve
      ligation was at its lowest level within 1 month. Although slightly increased
      afterwards, the head escape threshold maintained significantly lower than before
      injury until 3 months. We suggest that MAC1(+) macrophages contribute to the
      initiation of neuropathic pain by releasing cytokines/chemokines, and ED1(+)
      macrophages may contribute in maintaining the hypersensitivity under other
      mechanisms. CONCLUSION: Our results highlighted the heterogeneity and the
      plasticity of macrophages in response to the injury and provided further
      information on their potential involvement in neuropathic pain. Exploring the
      full spectrum of macrophage phenotypes in injured nerve is necessary. Individual
      macrophage population may be selectively targeted by cell-specific intervention
      for an effective treatment of neuropathic pain.

PMID- 22469909
TI  - Fatigue symptoms relate to systemic inflammation in patients with type 2
      diabetes.
AB  - Fatigue is frequent in patients with diabetes and this symptom appears to be more
      prominent in type 2 rather than type 1 diabetic subjects. Chronic inflammation
      represents one characteristic of type 2 diabetes that may contribute to fatigue
      symptoms. This possibility was assessed in a sample of 20 type 2 diabetic
      patients relatively to a group of 20 type 1 diabetic subjects. Specific
      dimensions of fatigue, including general fatigue, physical fatigue, reduced
      activity, mental fatigue and reduced motivation, were assessed using the
      Multidimensional-Fatigue-Inventory (MFI). Biological assays comprised the
      measurement of serum inflammatory markers [high-sensitive C-reactive-protein
      (hsCRP), high-sensitive interleukin-6 (hsIL-6), high-sensitive tumor-necrosis
      factor-alpha (hsTNF-alpha) and neopterin]. Clinical parameters including indexes
      of adiposity were collected. In comparison to type 1 diabetic subjects, patients
      with type 2 diabetes exhibited higher fatigue scores, notably in the dimensions
      of general fatigue, physical fatigue and reduced activity, together with greater
      levels of inflammatory markers that correlated with indexes of adiposity.
      Regression analyses controlling for diabetes duration, insulin treatment status,
      glycemic control and fasting status, indicated that levels of inflammatory
      markers, in particular hsIL-6, hsCRP and neopterin, were associated with MFI
      fatigue dimensions in type 2 diabetic patients. Mediation analyses revealed that
      adiposity did not significantly account for the relationship of inflammatory
      markers with fatigue scores albeit coefficient regressions decreased somewhat
      when this variable was controlled for in regression models. These findings
      indicate that systemic low-grade inflammation relates to fatigue symptoms in
      patients with type 2 diabetes and suggest the involvement of inflammatory
      processes in the pathophysiology of diabetes-related fatigue.

PMID- 22469910
TI  - Mitochondrial transcription factor A is a proinflammatory mediator in hemorrhagic
      shock.
AB  - Endogenous molecules released by dying cells [i.e., damage-associated molecular
      patterns (DAMPs)] after trauma and severe blood loss can activate pattern
      recognition receptors, leading to a cascade of inflammatory responses and organ
      injury. Mitochondrial transcription factor A (TFAM) is a transcription factor for
      mitochondrial DNA. TFAM is structurally related to high mobility group box 1
      (HMGB1), an important member of DAMPs. We, therefore, hypothesized that TFAM can
      be released into the circulation after hemorrhage to initiate inflammatory
      responses. In order to examine this hypothesis, male Sprague-Dawley rats were
      bled to and maintained at a mean arterial pressure of 40 mmHg for 90 min. They
      were then resuscitated with an equal volume of shed blood in the form of Ringer's
      lactate (i.e., low-volume resuscitation) over 60 min. TFAM levels in the serum
      were measured at 4 h after hemorrhage and resuscitation. Our results showed that
      serum levels of TFAM were more than doubled after hemorrhage and resuscitation.
      To further characterize TFAM's biological activity, we expressed recombinant rat
      TFAM with a GST-tag (GST-TFAM) in an E. coli expression system. The purity of GST
      TFAM was over 99% and it was immunoreactive for specific anti-TFAM antibodies.
      Using RAW 264.7 cells and primary rat peritoneal macrophages, we showed that GST
      TFAM dose-dependently increased TNF-alpha release. To determine the biological
      activity of GST-TFAM in vivo, GST-TFAM was intravenously injected in healthy male
      adult rats. Our results demonstrated that intravenous injection of GST-TFAM, not
      GST alone, upregulated circulating levels of pro-inflammatory cytokines,
      increased neutrophil infiltration to the lungs and caused organ injury in healthy
      animals. Thus, TFAM can act as a DAMP and may contribute to the initiation of
      inflammatory responses in hemorrhagic shock.

PMID- 22469911
TI  - Benchmarking urban acute care hospitals: efficiency and quality perspectives.
AB  - BACKGROUND: Over the last couple of decades, hospitals in the United States are
      facing pressures to maximize performance in terms of production efficiency and
      quality. An increasing emphasis on value-based purchasing on the part of third
      party payers as well as the prevalence of pay for performance initiatives create
      an imperative for more accurate assessments of health care provider performance.
      PURPOSES: The objectives of this study were to measure hospital performance in
      terms of both technical efficiency and quality using data envelopment analysis
      (DEA) models in urban acute care hospitals. METHODOLOGY/APPROACH: In this
      observational cross-sectional study of a nationally representative sample of 371
      urban acute care hospitals, hospital performance was assessed using slack-based
      additive DEA models. The technical inputs included in the DEA models were total
      number of beds setup and staffed, nonphysician full-time equivalent staffing, and
      nonpayroll operating expenses. The technical outputs were adjusted patient days,
      total number of outpatient visits, and training full-time equivalent, obtained
      from the American Hospital Association 2008 database. The quality measures used
      for the quality of care dimension of performance were survival rates for acute
      myocardial infarction, congestive heart failure, and pneumonia obtained from the
      Nationwide Inpatient Sample 2008 data. FINDINGS: Less than 20% of the sample
      hospitals were optimally performing for both quality and efficiency. Tobit
      regression analysis of the DEA scores found that public, small, teaching
      hospitals had higher DEA efficiency and quality scores. PRACTICE IMPLICATIONS:
      DEA is a promising tool for benchmarking both aspects of performance: efficiency
      and quality of hospitals. Because quality is a multidimensional construct, the
      choice of an appropriate composite quality measure has to be addressed in future
      research. However, incorporating quality into the DEA models would be a better
      reflection of the hospital product.

PMID- 22469912
TI  - Calcium blockers inhibit cyclosporine A-induced hyperreactivity of vascular
      smooth muscle cells.
AB  - Cyclosporine belongs to the group of the most commonly used immunosuppressants.
      Hypertension occurs in approximately 30% of patients treated with this drug.
      However, the pathogenesis of this occurrence has not been explained to date. The
      purpose of our study was to clarify the mechanisms leading to the evolution of
      hypertension induced by cyclosporine A (CsA). We examined the changes in
      transmission within receptors and around the receptors. We also aimed to
      elucidate the mechanisms responsible for averting arterial hyperresponsiveness
      induced by the drug. Experiments were performed on isolated and perfused tail
      arteries of Wistar rats. Tissues surrounding the artery were removed and the
      proximal segment (length of 2-3 cm) was used for cannulation. Cannulated arteries
      were placed in a 20-ml glass chamber (vertical position). The contraction force
      in our model was measured by an increased degree of perfusion pressure with a
      constant flow rate (approximately 1 ml/min). The results showed that in the
      presence of CsA, the concentration-response curves/phenylephrine (PHE) curve
      shifted to the left. Cyclosporine increased the reactivity of the arteries to
      PHE. This effect was directly linked to the increase in the receptor reserve. The
      analysis of the reactivity of vascular smooth muscle showed that CsA increased
      the influx of calcium ions from the extracellular to the intracellular area. No
      difference was found between the contraction triggered by Bay-K8644 in the
      presence of CsA and the control probe. The increase in perfusion pressure induced
      by CsA was blocked by L-type calcium channel blockers (nifidipine and diltiazem).
      The results from our experiments show that CsA increases the reactivity of
      vessels to the effect of catecholamines. CsA also enhances signal transmission
      between G-protein coupled receptors (GPCRs) and calcium channels. The activation
      of protein kinase C also plays a significant role in this process. Our results
      suggest that the best choice for the pharmacotherapy of hypertension induced by
      CsA would be calcium channel antagonists.

PMID- 22469913
TI  - Optimized extraction of calcium malate from eggshell treated by PEF and an
      absorption assessment in vitro.
AB  - Under optimized pulsed electric field (PEF) treatment for production of eggshell
      calcium malate (ESCM) by one-factor-at-a-time test and ternary quadratic
      regression orthogonal combination design (TQROCD), an absorption assessment of
      ESCM treated by the best conditions of PEF were performed in male mice with
      apparent calcium absorption rate (ACAR), serum alkalinity phosphatase (ALP),
      tartrate-resistant acid phosphatase (TRAP), serum calcium and serum phosphorus,
      length of femurs and skeletal calcium content were studied. The highest
      dissoluble calcium malate content (7.075 mg/mL) was obtained with the 6.0% malic
      acid, the electric field intensity of 20 kV/cm, and pulse duration of 24 MUs. In
      vitro, ESCM prepared by the best conditions of PEF at doses of 133.0 mg kg(-1) d(
      1) for 70 d not only significantly improve the ALP activity, the femur length and
      calcium content of bone of the mice (P<0.05) but also decreased the levels of
      TRAP (P<0.05). The ratio of calcium and phosphorus was in the normal range. PEF
      could be taken as a highly effective, environmentally friendly and energy-saving
      method for preparation of ESCM, which treated by PEF could promote the absorption
      of calcium in vitro, extraordinary can promote bone development and a healthy
      bone.

PMID- 22469914
TI  - Preparation and antimicrobial activity of some carboxymethyl chitosan acyl
      thiourea derivatives.
AB  - Acetyl, chloroacetyl and benzoyl thiourea derivatives of carboxymethyl chitosan
      (ATUCMCS, CATUCMCS, and BZTUCMCS) with comparable grafting degree were
      synthesized and their structures were characterized by FTIR spectroscopy and
      elemental analyses. The antimicrobial behaviors of CMCS and its derivatives
      against three types of bacteria [Bacillis subtilis (B. subtilis), Staphylococous
      aureus (S. aureus) and Escherichia coli (E. coli)] and three crop-threatening
      pathogenic fungi [Aspergillus fumigate (A. fumigate), Geotrichum candidum (G.
      candidum) and Candida albicans (C. albicans)] were investigated. The results
      indicated that the antibacterial and the antifungal activities of the acyl
      thiourea derivatives are much higher than that of the parent CMCS. The acyl
      thiourea derivatives were more potent in case of Gram-positive bacteria than Gram
      negative bacteria. This is illustrated for example by the values of minimum
      inhibitory concentration (MIC) of the ATUCMCS, CATUCMCS and BZTUCMCS against B.
      subtilis were 3.9, 15.6 and 62.5, respectively, while the MIC values of these
      derivatives against E. coli were 62.5, 125 and 500. Moreover, the antifungal
      activity of the CATUCMCS is higher than that of the acetyl and benzoyl thiourea
      derivatives. This may be due to the presence of chlorine atom.

PMID- 22469915
TI  - Realizing high magnetic moments in fcc Fe nanoparticles through atomic structure
      stretch.
AB  - We describe the realization of a high moment state in fcc Fe nanoparticles
      through a controlled change in their atomic structure. Embedding Fe nanoparticles
      in a Cu(1-x)Au(x) matrix causes their atomic structure to switch from bcc to fcc.
      Extended x-ray absorption fine structure (EXAFS) measurements show that the
      structure in both the matrix and the Fe nanoparticles expands as the amount of Au
      in the matrix is increased, with the data indicating a tetragonal stretch in the
      Fe nanoparticles. The samples were prepared directly from the gas phase by co
      deposition, using a gas aggregation source and MBE-type sources respectively for
      the nanoparticle and matrix materials. The structure change in the Fe
      nanoparticles is accompanied by a sharp increase in atomic magnetic moment,
      ultimately to values of ~2.5 +/- 0.3 MU(B)/atom .

PMID- 22469916
TI  - Pinning down a polymorphic parasite: new genetic and morphological descriptions
      of Eimeria macropodis from the Tammar wallaby (Macropus eugenii).
AB  - Identification of the protozoan parasite, Eimeria has traditionally relied on
      oocyst morphology, host range and life-cycle attributes. However, it is
      increasingly recognized that Eimeria species can vary in size and shape across
      their host range, an attribute known as 'polymorphism' that presents a unique
      challenge for identification. Advances in molecular tools hold promise for
      characterising Eimeria that may otherwise be misclassified based on morphology.
      Our study used morphologic and molecular traits of the oocyst life stage to
      identify a polymorphic parasite, Eimeria macropodis in a captive Tammar wallaby
      (Macropus eugenii) population in Australia. Molecular characterization
      highlighted the need to use multiple genetic markers (18S SSU and cytochrome c
      oxidase subunit I) to accurately identify E. macropodis owing to heterozygous
      alleles at the 18S SSU locus. This study provided an opportunity to assess the
      utility and shortcomings of morphologic and molecular techniques for 'pinning
      down' a polymorphic species. Moreover, our study was able to place E. macropodis
      in an evolutionary context and enhance resolution of the under-studied marsupial
      clade.

PMID- 22469917
TI  - hybridMANTIS: a CPU-GPU Monte Carlo method for modeling indirect x-ray detectors
      with columnar scintillators.
AB  - The computational modeling of medical imaging systems often requires obtaining a
      large number of simulated images with low statistical uncertainty which
      translates into prohibitive computing times. We describe a novel hybrid approach
      for Monte Carlo simulations that maximizes utilization of CPUs and GPUs in modern
      workstations. We apply the method to the modeling of indirect x-ray detectors
      using a new and improved version of the code MANTIS, an open source software tool
      used for the Monte Carlo simulations of indirect x-ray imagers. We first describe
      a GPU implementation of the physics and geometry models in fastDETECT2 (the
      optical transport model) and a serial CPU version of the same code. We discuss
      its new features like on-the-fly column geometry and columnar crosstalk in
      relation to the MANTIS code, and point out areas where our model provides more
      flexibility for the modeling of realistic columnar structures in large area
      detectors. Second, we modify PENELOPE (the open source software package that
      handles the x-ray and electron transport in MANTIS) to allow direct output of
      location and energy deposited during x-ray and electron interactions occurring
      within the scintillator. This information is then handled by optical transport
      routines in fastDETECT2. A load balancer dynamically allocates optical transport
      showers to the GPU and CPU computing cores. Our hybridMANTIS approach achieves a
      significant speed-up factor of 627 when compared to MANTIS and of 35 when
      compared to the same code running only in a CPU instead of a GPU. Using
      hybridMANTIS, we successfully hide hours of optical transport time by running it
      in parallel with the x-ray and electron transport, thus shifting the
      computational bottleneck from optical tox-ray transport. The new code requires
      much less memory than MANTIS and, asa result, allows us to efficiently simulate
      large area detectors.

PMID- 22469918
TI  - Inflammatory mediators in exhaled breath condensate of healthy donors and
      exacerbated COPD patients.
AB  - Samples of exhaled breath condensate (EBC) provide a convenient and non-invasive
      method to study inflammation in lung diseases. The aim of the present study was
      to evaluate and compare the inflammatory protein mediator levels in EBC from
      healthy donors (HD) and from patients with exacerbation of chronic obstructive
      pulmonary disease (COPD) using an EBC collection device with and without a
      coating of albumin as a carrier. We studied 13 HD and 26 patients with
      exacerbation of COPD. The concentrations of myeloperoxidase (MPO), IFNgamma and
      secretory leukocyte protease inhibitor (SLPI) in EBC were measured by
      immunoassays. The EBC samples from HD and COPD patients showed higher
      concentrations of MPO when samples were recovered with an albumin-coated device.
      Furthermore, levels of MPO in COPD patients were significantly higher than in HD.
      An inverse correlation was observed between MPO and spirometric parameters (FVC
      and FEV1). Almost all samples collected with the albumin-coated device showed
      higher amounts of IFNgamma and SLPI than those collected with the uncoated
      device. The levels of SLPI in COPD patients were significantly higher than in HD.
      A direct correlation was observed between FVC% predicted and SLPI. We concluded
      that coating the collection device with albumin increased the sensitivity of the
      technique, at least for measurements of MPO, SLPI and IFNgamma. Furthermore, the
      higher levels of MPO and SLPI and lower levels of IFNgamma in EBC from COPD
      patients could reflect the immunological status and the response of lung
      parenchyma to treatment during the exacerbation of the illness.

PMID- 22469919
TI  - Water soluble extended naphthalene diimides as pH fluorescent sensors and G
      quadruplex ligands.
AB  - Extended naphthalene diimides (NDIs) fused to 1,4-dihydropyrazine-2,3-dione,
      containing two solubilizing moieties, have been synthesized. Fluorescence spectra
      of the new NDIs were remarkably affected by pH, as the second deprotonation of
      the dihydropyrazinedione moiety (pK(a) 6.9) switched off the emission. Binding to
      a G-quadruplex folded oligonucleotide and stoichiometry were evaluated by FRET
      melting assay and CD analysis. G-quadruplex binding was strongly enhanced
      shifting from pH 7.4 to pH 6.0 as a consequence of the dihydropyrazinedione
      moiety protonation. Cytotoxicity studies using two human telomerase-positive cell
      lines (HT29 and A549) revealed that the best G-quadruplex ligand was very active
      against the colon cell line, with an EC(50) of 300 nM.

PMID- 22469920
TI  - Neuronal nitric oxide synthase (nNOS) immunoreactivity in the olfactory system of
      a cartilaginous fish.
AB  - Nitric oxide is a regulative molecule with important roles in the olfactory
      system of vertebrates. Chondrichtyans have a key position in vertebrate evolution
      and nothing is known about nitric oxide in their olfactory system. Aim of this
      work was to investigate the neuronal nitric oxide synthase (nNOS)
      immunoreactivity in the olfactory system of the shark Scyliorhinus canicula.
      Because nitric oxide is often related to GABA in the olfactory system, also the
      distribution of GABA and its synthesis enzyme GAD has been investigated. In the
      olfactory epithelium scattered cells in the basal and medial zone of the
      epithelium thickness presented nNOS-like immunoreactivity. In the olfactory bulb
      the nNOS-like immunoreactivity has been highlighted in nerve fibers around some
      blood vessels and in scattered GABAergic granule cells. The presence of nNOS in
      the olfactory system of S. canicula is overall lesser than that described in
      other vertebrates, even if nitric oxide probably keeps some essential functions.

PMID- 22469921
TI  - Tiam1, negatively regulated by miR-22, miR-183 and miR-31, is involved in
      migration, invasion and viability of ovarian cancer cells.
AB  - Tiam1 has been implicated in the invasive phenotype of various carcinomas.
      However, its role in ovarian cancer remains to be elucidated, including its
      upstream regulatory mechanisms. In the present study, we examined the
      differential expression of Tiam1 in 10 normal ovarian tissues and 17 paired
      primary and corresponding metastatic ovarian cancer tissues by semi-quantitative
      immunohistochemistry. It was found that Tiam1 expression was remarkably increased
      in both primary and metastatic ovarian cancer tissues relative to normal ovarian
      tissues. Loss-of-function study revealed that downregulation of Tiam1 in SKOV-3ip
      and HO-8910PM cells lead to reduced cell migration and invasion, and growth
      inhibition without significantly affecting cell apoptosis. Subsequent regulatory
      study further confirmed the negative regulatory effects of miR-22, miR-183 and
      miR-31 on Tiam1 expression. Taken together, our data suggested that Tiam1 may be
      involved in the aggressive behavior of ovarian cancer, and differential
      expression profiles of microRNA (miRNA) may contribute to the dysregulation of
      Tiam1 abundance, which contributes to the invasive, migratory and viability
      properties of ovarian cancer cells.

PMID- 22469922
TI  - Comparative survey of PAHs incidence in Portuguese traditional meat and blood
      sausages.
AB  - Sixteen polycyclic aromatic hydrocarbons (PAHs) in representative traditional
      sausages produced in "Tras-os-Montes" and "Alentejo", were determined. Light PAHs
      represented similar overall contents in both regions and showed close decreasing
      order patterns (ACY, PHE, FLR and NAP), irrespective of the product type
      considered. Amongst the carcinogenic/mutagenic PAHs analyzed (PAH8), both regions
      also had greater contents associated to BaA and CHR, with slightly higher values
      for the former compound in "Alentejo" and, oppositely, for the later in "Tras-os
      Montes". However, their quantitative comparison showed that the general mean
      total PAH content found in "Tras-os-Montes" was almost 3-fold higher than in
      similar products from "Alentejo" and this factor was about 8-fold superior when
      the PAH8 and PAH4 indicators were compared, expressing benzo[a]pyrene toxic
      equivalencies (BaPE), 15 times (total mean toxicity), 34 times (PAH8) and 9 times
      (PAH4) higher. In general terms, the mean BaP content of all analyzed samples
      from "Alentejo" was 0.41 MUg kg(-1). Differently that value in "Tras-os-Montes"
      reached 3.57 MUg kg(-1), expressing concerning average contents of 5.35, 5.87 and
      4.51 MUg kg(-1) in Chourico de Carne, Moura and Salpicao sausages, respectively.

PMID- 22469923
TI  - Massive childhood lead poisoning: the price of Nigerian gold.

PMID- 22469924
TI  - Performance evaluation of a sub-millimetre spectrally resolved CT system on high-
      and low-frequency imaging tasks: a simulation.
AB  - We are developing a photon-counting silicon strip detector with 0.4 * 0.5 mm2
      detector elements for clinical CT applications. Except for the limited detection
      efficiency of approximately 0.8 for a spectrum of 80 kVp, the largest
      discrepancies from ideal spectral behaviour have been shown to be Compton
      interactions in the detector and electronic noise. Using the framework of
      cascaded system analysis, we reconstruct the 3D MTF and NPS of a silicon strip
      detector including the influence of scatter and charge sharing inside the
      detector. We compare the reconstructed noise and signal characteristics with a
      reconstructed 3D MTF and NPS of an ideal energy-integrating detector system with
      unity detection efficiency, no scatter or charge sharing inside the detector,
      unity presampling MTF and 1 * 1 mm2 detector elements. The comparison is done by
      calculating the dose-normalized detectability index for some clinically relevant
      imaging tasks and spectra. This work demonstrates that although the detection
      efficiency of the silicon detector rapidly drops for the acceleration voltages
      encountered in clinical computed tomography practice, and despite the high
      fraction of Compton interactions due to the low atomic number, silicon detectors
      can perform on a par with ideal energy-integrating detectors for routine imaging
      tasks containing low-frequency components. For imaging tasks containing high
      frequency components, the proposed silicon detector system can perform
      approximately 1.1-1.3 times better than a fully ideal energy-integrating system.

PMID- 22469925
TI  - The Health Physics Society: an affiliate of the International Radiation
      Protection Association (IRPA). Prospectus.

PMID- 22469926
TI  - Editor's note on Fukushima.

PMID- 22469927
TI  - Introduction to the special issue on the U.S. Response to the Fukushima accident.
      Introduction.

PMID- 22469928
TI  - DoD's Medical Radiobiology Advisory Team: experts on the ground.
AB  - The Medical Radiobiology Advisory Team (MRAT) is the operations arm of the Armed
      Forces Radiobiology Research Institute (AFRRI), located at Naval Support Activity
      in Bethesda, MD. AFRRI is internationally recognized as expert in the biological
      effects of ionizing radiation research, training, and mitigation. During the U.S.
      Department of Defense's (DoD) response to the Fukushima Daiichi reactor incident,
      Operation Tomodachi, the MRAT provided guidance and advice to the U.S. Military
      leaders in Japan. This support helped ensure the safety of U.S. service members,
      family members, and civilians and supported the humanitarian relief in a
      coordinated effort with the Government of Japan (GOJ).

PMID- 22469929
TI  - Aerial measuring system in Japan.
AB  - The U.S. Department of Energy/National Nuclear Security Administration's
      (DOE/NNSA) Aerial Measuring System (AMS) deployed personnel and equipment to
      partner with the U.S. Forces in Japan (USFJ) to conduct multiple aerial
      radiological surveys. These were the first and most comprehensive sources of
      actionable information for U.S. interests in Japan and provided early
      confirmation to the Government of Japan as to the extent of the release from the
      Fukushima Daiichi Nuclear Power Plant. Many challenges were overcome quickly
      during the first 48 h, including installation and operation of Aerial Measuring
      System equipment on multiple USFJ aircraft, flying over difficult terrain, and
      flying with USFJ pilots who were unfamiliar with the Aerial Measuring System
      flight patterns. These factors combined to make for a programmatically
      unanticipated situation. In addition to the challenges of multiple and ongoing
      releases, integration with the Japanese government to provide valid aerial
      radiological survey products that both military and civilian customers could use
      to make informed decisions was extremely complicated. The Aerial Measuring System
      Fukushima response provided insight into addressing these challenges and gave way
      to an opportunity for the expansion of the Aerial Measuring System's mission
      beyond the borders of the U.S.

PMID- 22469930
TI  - Environmental measurements in an emergency:  this is not a drill.
AB  - Emergency responders from the Department of Energy are trained regularly to
      assess the environmental consequences of a radiological or nuclear incident.
      While drills and exercises are highly effective tools in rehearsing for an
      emergency, the accidents at the Fukushima Daiichi Nuclear Power Plants presented
      real-world complexities that are difficult or impossible to simulate in such
      training. Customarily, the modeled hypothetical event used to create a drill or
      exercise data set is simple, well defined, and closely resembles conventional
      assumptions about the type of that event. Consequently, the modeling performed by
      players from the outset closely resembles the planner's hypothetical event. This
      approach also entails idealized, uniform data in the simulated plume and ground
      deposition scenarios created for the drill that match the modeling closely. The
      real-world event that occurred in Japan sharply deviated from the simple picture
      ordinarily created for drills and exercises that typically involve a release of
      radioactivity that is of short duration, a single puff with constant meteorology,
      or simple deviation such as a wind shift to bifurcate the plume. In the very
      early stages, accurate plume and deposition model predictions were difficult to
      produce due to the lack of field monitoring data and other information. In
      contrast to drills and exercises where plant monitoring data is available, there
      was much less plant monitoring data, essentially no reactor state information,
      and the meteorological conditions and releases were much more complex.
      Inevitably, the measurements in Japan were not homogeneous, thus presenting
      technical challenges to assessors tasked with ensuring the quality of the
      finished assessments and data products for government officials, the responder
      community, and the public. In this paper, examples of some operational real-world
      complexities are considered. Procedures, measurements, or radiological
      assessments from the Fukushima response are not in the purview of this paper.

PMID- 22469931
TI  - Impact of the Fukushima nuclear accident on background radiation doses measured
      by control dosimeters in Japan.
AB  - After the 9.0 magnitude earthquake and subsequent massive tsunami on 11 March
      2011 in Japan, several reactors at the Fukushima Daiichi Nuclear Power Plant
      suffered severe damage. There was immediate participation of U.S. Navy vessels
      and other United States Department of Defense (DoD) teams that were already in
      the area at the time of the disaster or arrived shortly thereafter. The correct
      determination of occupational dose equivalent requires estimation of the
      background dose component measured by control dosimeters, which is subsequently
      subtracted from the total dose equivalent measured by personal dosimeters. The
      purpose of the control dosimeters is to determine the amount of radiation dose
      equivalent that has accumulated on the dosimeter from background or other non
      occupational sources while they are in transit or being stored. Given the release
      of radioactive material and potential exposure to radiation from the Fukushima
      Daiichi Nuclear Power Plant and the process by which the U.S. Navy calculates
      occupational exposure to ionizing radiation, analysis of pre- and post-event
      control dosimeters is warranted. Several hundred historical dose records from the
      Naval Dosimetry Center (NDC) database were analyzed and compared with the post
      accident dose equivalent data of control dosimeters. As result, it was shown that
      the dose contribution of the radiation and released radiological materials from
      the Fukushima nuclear accident to background radiation doses is less than 0.375
      MUSv d for shallow and deep photon dose equivalent. There is no measurable effect
      on neutron background exposure. The latter has at least two important
      conclusions. First, the NDC can use doses measured by control dosimeters at
      issuing sites in Japan for determination of personnel dose equivalents; second,
      the dose data from control dosimeters prior to and after the Fukushima accident
      may be used to assist in dose reconstruction of non-radiological (non-badged)
      personnel at these locations.

PMID- 22469932
TI  - Emergency response health physics.
AB  - Health physics is an important discipline with regard to understanding the
      effects of radiation on human health. This paper aims to illustrate the unique
      challenges presented to the health physicist or analyst of radiological data in a
      large-scale emergency.

PMID- 22469933
TI  - U.S. EPA response to the Fukushima Daiichi Nuclear Power Plant accident.
AB  - During the spring of 2011, the U.S. Environmental Protection Agency (EPA) used
      its national radiation monitoring and sampling system, RadNet, to detect,
      identify, and inform the public about radioactive material in the United States
      resulting from Japan's Fukushima Daiichi Nuclear Power Plant release. The RadNet
      system monitors ambient air, drinking water, precipitation, and pasteurized milk
      for radionuclides. To supplement its existing stationary (fixed) continuous air
      monitoring system, EPA deployed additional air monitors to Saipan, Guam, and
      locations in the western United States. The Agency also accelerated the regular
      quarterly sampling of milk and drinking water and collected an additional round
      of samples. For two months, staff located at EPA's Headquarters Emergency
      Operations Center, west coast regional offices, and National Air and Radiation
      Environmental Lab worked seven days a week to handle the increased radiochemical
      sample analysis from air filters, precipitation, drinking water, and milk;
      provide interagency scientific input; and answer press and public inquiries.
      EPA's data was consistent with what was expected from the Fukushima Daiichi
      Nuclear Power Plant release. The levels of radioactivity were so low that the
      readings from the near-real-time RadNet air monitors stayed within normal
      background ranges. Detailed sample analyses were needed to identify the
      radionuclides associated with the release. Starting at the end of April and
      continuing through May 2011, levels of radioactive material decreased as
      expected.

PMID- 22469934
TI  - The Fukushima radiological emergency and challenges identified for future public
      health responses.
AB  - On 11 March 2011, northern Japan was rocked by first a magnitude 9.0 earthquake
      off the eastern coast and then an ensuing tsunami. The Fukushima Daiichi Nuclear
      Power Plant complex was hit by these twin disasters, and a cascade of events was
      initiated that led to radionuclide releases causing widespread radioactive
      contamination of residential areas, agricultural land, and coastal waters.
      Radioactive material from Japan was subsequently transmitted to locations around
      the globe, including the U.S. The levels of radioactive material that arrived in
      the U.S. were never large enough to be a concern for health effects, but the
      presence of this material in the environment was enough to create a public health
      emergency in the U.S. The radiation safety and public health communities in the
      U.S. are identifying challenges they faced in responding to this incident. This
      paper discusses three of those challenges: (1) The growing shortage of trained
      radiation subject matter experts in the field of environmental transport and
      dosimetry of radionuclides; (2) the need to begin expressing all radiation
      related quantities in terms of the International System of Units; and (3) the
      need to define when a radiation dose is or is not one of "public health concern."
      This list represents only a small subset of the list of challenges being
      identified by public health agencies that responded to the Fukushima incident.
      However, these three challenges are fundamental to any radiological emergency
      response. Addressing them will have a significant positive impact on how the U.S.
      responds to the next radiological emergency.

PMID- 22469939
TI  - Comment on Hoffman et al.

PMID- 22469940
TI  - Docetaxel in the treatment of children with refractory or relapsed
      hepatoblastoma.
AB  - We report on the use of single-agent docetaxel (100 mg/m(2) in children >10 kg,
      3.3 mg/kg in children <10 kg), given as a 1-hour infusion at 21-day intervals in
      5 children with relapsed or refractory hepatoblastoma. One patient achieved
      complete remission of pulmonary metastases after 2 courses of docetaxel and
      remains well 10 years later, after completion of 13 courses of docetaxel and
      whole-lung radiotherapy. One patient showed a partial response to docetaxel based
      on alpha-fetoprotein measurements. Docetaxel shows some activity in progressive
      hepatoblastoma in this small case series and is a potential drug for future study
      in this disease.

PMID- 22469941
TI  - Hepatoblastoma in a mosaic trisomy 18 patient.
AB  - We report a case of hepatoblastoma in a 10-year-old girl with mosaic-type trisomy
      18. A comprehensive literature review reveals only 2 cases involving mosaic
      trisomy 18 patients. Our patient underwent an abbreviated chemotherapy course
      before complete surgical resection. Her hepatoblastoma did not contain cells with
      trisomy 18. The conservative management approach resulted in a successful
      outcome; she remains disease free >2 years after surgery. Along with presenting a
      literature review, this report demonstrates a favorable outcome in a mosaic
      trisomy 18 child with hepatoblastoma where tumor cells lacked a trisomy 18
      karyotype.

PMID- 22469942
TI  - Thymic mucosa-associated lymphoid tissue lymphoma in an adolescent girl.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is very rare in children. We
      report the first case of pediatric thymic MALT lymphoma in an adolescent Asian
      girl. She presented with chest pain, dyspnea, and low-grade fever. A large
      anterior mediastinal mass was biopsied that confirmed the diagnosis of MALT
      lymphoma with trisomy 18. The patient had secondary immunodeficiency with low NK
      cell count and high IgA and IgG levels. Because of the advanced stage and the
      presence of trisomy 18, she was treated with cyclophosphamide, vincristine,
      prednisone, and rituximab, followed by involved-field radiotherapy. She is
      currently undergoing maintenance therapy with rituximab and remains in complete
      remission at 13 months from diagnosis. Thymic MALT lymphoma should be suspected
      in any Asian child with a cystic thymic mass and autoimmune disease or
      hyperglobinemia. Because of the slow proliferation rate of this type of lymphoma,
      a long-term follow-up is needed.

PMID- 22469943
TI  - Invasive inflammatory myofibroblastic tumor of the spleen treated with partial
      splenectomy in a child.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare benign tumor that can be found
      in intra-abdominal organs such as the liver, intestine, extrahepatic bile ducts,
      and mesentery. The spleen is an extremely unusual location for an IMT. The
      authors report the case of a 14-year-old boy with invasive splenic IMT, present a
      review on the current literature about childhood splenic IMT, and emphasize the
      necessity of total excision of the tumor together with tumor-invaded surrounding
      tissues.

PMID- 22469944
TI  - Hemophagocytosis by leukemic megakaryoblasts in acute myeloid leukemia
      (megakaryoblastic) with t(1;22)(p13;q13);RBM15-MKL1.
AB  - Acute megakaryoblastic leukemia is a rare variant of acute myeloid leukemia,
      whereby leukemic blasts display characteristic morphologic and phenotypic
      features indicating megakaryocytoid differentiation. A distinct entity
      characterized by the t(1;22)(p13;q13) translocation, resulting in the RBM15-MKL1
      fusion oncogene, has been recently recognized. This is predominantly a disease
      afflicting infants and displays characteristic clinical features. We present a
      case of acute megakaryoblastic leukemia with t(1;22)(p13;q13) along with a
      discussion of the current understanding of the molecular biology of RBM15-MKL1.
      This case also displayed striking and unusual morphologic appearances including
      extensive hemophagocytosis by leukemic blasts, which has not been previously
      reported for this particular type of leukemia.

PMID- 22469945
TI  - Development of anaplastic Wilms tumor and subsequent relapse in a child with
      diaphanospondylodysostosis.
AB  - Diaphanospondylodysostosis (DSD) is a rare skeletal dysplasia syndrome resulting
      from disordered mesenchymal differentiation. Children with DSD generally die in
      utero or during the first month of life from severe thoracic insufficiency
      syndrome. An association of DSD with nephroblastomatosis has been observed, but
      the natural history of such nephroblastomatosis remains poorly characterized due
      to the rarity of the underlying condition. We describe a patient with DSD who
      developed bilateral hyperplastic nephroblastomatosis that ultimately evolved into
      therapy-resistant anaplastic Wilms tumor (nephroblastoma).

PMID- 22469946
TI  - Sporadic adenocarcinoma of the colon in children:  case series and review of the
      literature.
AB  - BACKGROUND: Adenocarcinoma of the colon is rare in pediatric patients and thus
      not much is known about its clinical and imaging characteristics. OBSERVATIONS:
      We present 4 adolescents with an average age of 15 years who present with several
      month histories of significant weight loss and abdominal pain. All had an
      abdominal and pelvic computed tomography scan, which revealed an adenocarcinoma
      in the colon. One patient had metastatic disease at diagnosis. The main treatment
      was primary resection and chemotherapy. Two of the children had a family history
      of colon cancer. Our case series depicts similarities and differences in disease
      presentation, tumor location, pattern of metastasis, genetics, management between
      adults and children and conducts a review of the relevant literature concerning
      adenocarcinoma in the pediatric population. CONCLUSIONS: In children, this
      disease has more aggressive histologies and presents more frequently in an
      advanced stage. This is because it is not a diagnosis often considered, leading
      to poorer outcomes. When patients present in the correct clinical context, the
      possibility of colonic adenocarcinoma should be considered in the differential
      diagnosis, which may in turn lead to better outcomes.

PMID- 22469947
TI  - Skin involvement in a newborn with down syndrome and transient myeloproliferative
      disorder.

PMID- 22469948
TI  - Mucoepidermoid carcinoma of the parotid as a secondary malignancy after
      chemotherapy in a child with neuroblastoma.
AB  - Secondary neoplasms are not reported frequently after neuroblastoma, which until
      recently was a cancer with limited long-term survival. Although salivary gland
      tumors in children and adolescents may be idiopathic, they are seen more often
      after head and neck radiation. We report a child with stage 4 neuroblastoma
      treated with high-dose multiagent chemotherapy without radiation therapy to his
      neck who, within 1 year of treatment, developed a low-grade but large and locally
      aggressive mucoepidermoid carcinoma of his parotid gland further characterized by
      a t(11;19)(q21;p13.1). Our patient extends the spectrum of secondary neoplasms
      after neuroblastoma. 

PMID- 22469949
TI  - Finding Hsp90 inhibitors by drug repurposing: the power of chemical genetics.

PMID- 22469950
TI  - HemITAM signaling by CEACAM3, a human granulocyte receptor recognizing bacterial
      pathogens.
AB  - Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) belong to the
      immunoglobulin superfamily and contribute to cell-cell adhesion and signal
      modulation in various tissues. In humans, several CEACAMs are targeted by
      pathogenic bacteria. One peculiar member of this family, CEACAM3, is exclusively
      expressed by human granulocytes and functions as an opsonin-independent
      phagocytic receptor for CEACAM-binding bacteria. Here, we will discuss CEACAM3
      dependent processes by summarizing recent insight into the phosphotyrosine-based
      signaling complex formed upon CEACAM3 engagement. Compared to different well
      studied phagocytic receptors, such as Fcgamma receptors and Dectin-1, CEACAM3
      appears as an example of a hemITAM-containing innate immune receptor, which
      promotes rapid internalization and intracellular destruction of a diverse group
      of CEACAM-binding bacteria. The particular efficiency of CEACAM3 arises from the
      direct coupling of upstream activators and downstream effectors of the small
      GTPase Rac by the cytoplasmic domain of CEACAM3, which co-ordinates actin
      cytoskeleton re-arrangements and bactericidal effector mechanisms of
      granulocytes.

PMID- 22469951
TI  - Emerging role of autophagy during ischemia-hypoxia and reperfusion in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignancy found in the
      liver. Autophagy is the intracellular bulk degradation process for long-lived
      proteins and dysfunctional organelles. In this study, we report that autophagy
      plays a role in HCC cell proliferation in response to ischemia-hypoxia (I/H) and
      reperfusion and discuss its potential therapeutic implications. By establishing a
      simulated model in cultured HepG2 (p53 wild-type) and Hep3B (p53 null) hepatoma
      cells in vitro, we found that exposure to I/H induced a significant increase in
      microtubule-associated protein 1 light chain 3 (LC3) lipidation and subsequent
      LC3 puncta formation. While the proliferation of HCC cells was stimulated upon
      acute I/H exposure compared to that of control, inhibition of autophagy by
      autophagy-related protein 7 interference abolished it. In addition, the steady
      state levels of sequestosome 1 (p62) in both HepG2 and Hep3B cells were reduced
      following I/H exposure, supporting the notion that acute I/H induces autophagy.
      Intriguingly, the p62 level further decreased during reperfusion following I/H,
      accompanied by increased LC3 lipidation. The intracellular reactive oxygen
      species (ROS) accumulated during acute I/H exposure and persisted through
      reperfusion in both HepG2 and Hep3B cells and the ROS levels increased at a much
      faster rate during reperfusion than during I/H periods in both cells. Autophagy
      functions as a promoter for HCC cell survival during acute I/H and reperfusion
      and this also points to potential therapy for hepatoma by perturbing the acute
      I/H-reperfusion-autophagy axis.

PMID- 22469952
TI  - Synergistic anticancer activity of curcumin and bleomycin: an in vitro study
      using human malignant testicular germ cells.
AB  - Testicular cancer is the most common cancer among young men of reproductive age.
      Bleomycin is a frequently used drug for the treatment of several malignancies and
      is part of the chemotherapy protocols used for testicular cancer; however, side
      effects are common. Bleomycin causes an increase in oxidative stress which has
      been shown to induce apoptosis in cancer cells. Curcumin (diferuloylmethane), an
      active component of the spice turmeric, has been demonstrated to induce apoptosis
      in a number of malignancies. However, to date no study has been carried out to
      elucidate its anticancer activity and interaction with bleomycin in testicular
      cancer cells. In this study, we investigated and compared the effects of
      curcumin, bleomycin and hydrogen peroxide (H2O2) on apoptotic signaling pathways.
      Curcumin (20 uM), bleomycin (400 ug/ml) and H2O2 (400 uM) incubation for 24 h
      decreased the viability of NTera-2 cells, and increased caspase-3, -8 and -9
      activities, Bax and cytoplasmic cytochrome c levels and decreased Bcl-2 levels.
      The concurrent use of curcumin with bleomycin induced caspase-3, -8 and -9
      activities to a greater extent in NTera-2 cells than the use of each drug alone.
      Our observations suggest that the effects of curcumin and bleomycin on apoptotic
      signaling pathways are synergistic. Therefore, we propose to use curcumin
      together with bleomycin to decrease its therapeutic dose and, therefore, its side
      effects.

PMID- 22469953
TI  - Evaluation of high-resolution peripheral quantitative computed tomography, finite
      element analysis and biomechanical testing in a pre-clinical model of
      osteoporosis: a study with odanacatib treatment in the ovariectomized adult
      rhesus monkey.
AB  - This study aimed to validate finite element analysis (FEA) estimation of
      strength, identify high-resolution peripheral quantitative computed tomography
      (HR-pQCT) measures correlating with strength, and evaluate the precision of HR
      pQCT measurements to longitudinally monitor effects of osteoporosis treatment in
      ovariectomized (OVX) non-human primates (NHPs). HR-pQCT images were acquired in
      three groups of NHPs: Intact (n=10), OVX-odanacatib treated (OVX-ODN 30 mg/kg,
      n=10) and OVX-vehicle treated (OVX-Veh, n=10) at the ultradistal (UD) and distal
      1/3 radii and tibia at 12, 16 and 20 months. FEA estimates of bone strength using
      the Pistoia criterion were validated by ex-vivo mechanical compression
      (r(2)=0.95) of the UD radius. Single linear regressions of FEA-determined
      ultimate stress showed high correlation with HR-pQCT derived parameters: integral
      vBMD (r(2)=0.86), bone volume fraction (r(2)=0.84) and cortical thickness
      (r(2)=0.79). Precision of HR-pQCT measurements, obtained from an excised radius
      and tibia, showed low variation (CV=0.005%-5.6%) and helped identify possible
      sources of error. Comparison of OVX-Veh and Intact groups showed decreases in
      bone parameters demonstrating trends consistent with bone loss. Comparison of OVX
      ODN and OVX-Veh groups showed a treatment effect with increases in bone
      parameters: integral vBMD (477+/-27 vs. 364+/-22 mgHA/cm(3)) and cortical
      thickness (Ct.Th) (0.90+/-0.07 vs. 0.64+/-0.04 mm) at the UD radius, Ct.Th
      (2.15+/-0.28 vs. 1.56+/-0.08 mm) at the distal 1/3 radius. Axial compression peak
      stress calculated and obtained experimentally showed the OVX-ODN group was 33%
      stronger than the OVX-Veh group. We conclude that HR-pQCT and FEA serve as robust
      techniques to longitudinally monitor bone parameters and strength in NHP's.

PMID- 22469954
TI  - Cluster analysis of the national weight control registry to identify distinct
      subgroups maintaining successful weight loss.
AB  - The National Weight Control Registry (NWCR) is the largest ongoing study of
      individuals successful at maintaining weight loss; the registry enrolls
      individuals maintaining a weight loss of at least 13.6 kg (30 lb) for a minimum
      of 1 year. The current report uses multivariate latent class cluster analysis to
      identify unique clusters of individuals within the NWCR that have distinct
      experiences, strategies, and attitudes with respect to weight loss and weight
      loss maintenance. The cluster analysis considers weight and health history,
      weight control behaviors and strategies, effort and satisfaction with maintaining
      weight, and psychological and demographic characteristics. The analysis includes
      2,228 participants enrolled between 1998 and 2002. Cluster 1 (50.5%) represents a
      weight-stable, healthy, exercise conscious group who are very satisfied with
      their current weight. Cluster 2 (26.9%) has continuously struggled with weight
      since childhood; they rely on the greatest number of resources and strategies to
      lose and maintain weight, and report higher levels of stress and depression.
      Cluster 3 (12.7%) represents a group successful at weight reduction on the first
      attempt; they were least likely to be overweight as children, are maintaining the
      longest duration of weight loss, and report the least difficulty maintaining
      weight. Cluster 4 (9.9%) represents a group less likely to use exercise to
      control weight; they tend to be older, eat fewer meals, and report more health
      problems. Further exploration of the unique characteristics of these clusters
      could be useful for tailoring future weight loss and weight maintenance programs
      to the specific characteristics of an individual.

PMID- 22469955
TI  - Prevalence and familial patterns of night eating in the Quebec adipose and
      lifestyle investigation in youth (QUALITY) study.
AB  - The prevalence and familial patterns of night eating syndrome (NES) in families
      enrolled in the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY)
      study was examined. Families (n = 395; one child, mother, and father for whom at
      least one parent was obese or had abdominal obesity) completed the Night Eating
      Questionnaire (NEQ) as part of a longitudinal study on the development of
      metabolic disease in children at risk for obesity. Responses on the NEQ were used
      to establish a diagnosis of NES and to determine the correlation and heritability
      of NES symptoms in families. Using comprehensive research diagnostic criteria,
      full threshold NES was rare: 0% of children, 0.5% of mothers, and 0.3% of fathers
      met criteria. When controlling for age, sex, and BMI, NEQ scores of spouses were
      not significantly correlated, but mothers' NEQ scores were significantly
      correlated with the scores of both sons (r = 0.19, P < 0.001) and daughters (r =
      0.15, P = 0.05). The heritability of NEQ scores was 0.24 when controlling for
      age, sex, and BMI. These findings replicate previous research suggesting a low
      prevalence of night eating behavior in children and the aggregation of NES in
      families.

PMID- 22469956
TI  - In support of breastfeeding.

PMID- 22469961
TI  - Congenital disorders of glycosylation.
AB  - Congenital disorders of glycosylation (CDG) are a group of disorders involving a
      defect in the synthesis of oligosaccharides. Oligosaccharides are fundamental for
      protein stability and cellular communication and are present in almost every cell
      in the human body. A defect in the synthesis of oligosaccharides can result in
      multisystemic effects. Congenital disorders of glycosylation are classified into
      type I and type II disorders, each with subgroup classifications. All CDGs are
      autosomal recessive disorders, with CDG type I being the most common. This
      article will explore both types of CDG, their clinical presentation, diagnosis,
      and management.

PMID- 22469962
TI  - Congenital disorder of glycosylation: a case presentation.
AB  - Congenital disorders of glycosylation (CDG) are a group of rare genetically
      inherited disorders that involve the malfunction of attaching sugar molecules to
      lipids, proteins, or other organic molecules through an enzymatic process. The
      resulting defect in glycoprotein and glycolipid synthesis often has a
      heterogeneous range of multisystemic effects ranging from mild dysmorphism to
      profound organ failure and subsequent death. There are 2 types of CDG, type I and
      type II, with multiple subtypes within each. This column is a case presentation
      about an infant who presented with CDG type Ik.

PMID- 22469959
TI  - Necrotizing enterocolitis risk: state of the science.
AB  - Necrotizing enterocolitis (NEC) is the most common cause of gastrointestinal
      related morbidity and mortality in the neonatal intensive care unit (NICU). Its
      onset is sudden and the smallest, most premature infants are the most vulnerable.
      Necrotizing enterocolitis is a costly disease, accounting for nearly 20% of NICU
      costs annually. Necrotizing enterocolitis survivors requiring surgery often stay
      in the NICU more than 90 days and are among those most likely to stay more than 6
      months. Significant variations exist in the incidence across regions and units.
      Although the only consistent independent predictors for NEC remain prematurity
      and formula feeding, others exist that could increase risk when combined.
      Awareness of NEC risk factors and adopting practices to reduce NEC risk,
      including human milk feeding, the use of feeding guidelines, and probiotics, have
      been shown to reduce the incidence of NEC. The purpose of this review is to
      examine the state of the science on NEC risk factors and make recommendations for
      practice and research.

PMID- 22469964
TI  - Adolescent girls: a vulnerable population.
AB  - Issues key to adolescent girls are discussed. The importance and relevance of the
      adolescent girl as a vulnerable population are explicated. Potential
      interventions and how they impact global health are explained. Nursing theory and
      model use are examined. Pyschosocial developmental theory is applied. Strategies
      to improve outcomes are explored.

PMID- 22469965
TI  - Premedication for neonatal intubation: which medications are recommended and why.

PMID- 22469966
TI  - The effect of music-based listening interventions on the volume, fat content, and
      caloric content of breast milk-produced by mothers of premature and critically
      ill infants.
AB  - PURPOSE: Maternal breast milk is considered the nutritional "gold standard" for
      all infants, especially premature infants. However, preterm mothers are at risk
      of not producing adequate milk. Multiple factors affect the production of milk,
      including stress, fatigue, and the separation of the breastfeeding dyad-for
      example, when mother or infant is hospitalized. The purpose of this study was to
      examine the effects of listening and visual interventions on the quantity and
      quality of breast milk produced by mothers using a double electric breast pump.
      SUBJECTS: Mothers of 162 preterm infants were randomly assigned to 1 of 4 groups.
      METHODS: The control group received standard nursing care, whereas mothers in the
      3 experimental groups additionally listened to a recording of 1 of 3 music-based
      listening interventions while using the pump. RESULTS: Mothers in the
      experimental groups produced significantly more milk (P < .0012). Mothers in
      these groups also produced milk with significantly higher fat content during the
      first 6 days of the study.

PMID- 22469967
TI  - Normative cultural values and the experiences of Mexican-American mothers in the
      neonatal intensive care unit.
AB  - PURPOSE: To explore the experiences of Mexican-American mothers who have had
      infants in the neonatal intensive care unit (NICU). PARTICIPANTS: A convenience
      sample of 15 English-speaking, Mexican-American women was interviewed. DESIGN:
      The study used an exploratory qualitative approach. METHODS: Data collection was
      conducted through audiotaped, transcribed, semistructured, individual interviews
      and field notes. The 5 normative cultural values for Latino families-(1)
      simpatia, (2) personalismo, (3) respeto, (4) familismo, and (5) fatalismo-were
      used as a sensitizing framework to guide data interpretation. RESULTS: The
      women's discussions of their NICU experiences clearly reflect the 5 normative
      Latino cultural values. Positive and negative exemplars of these values are
      provided as evidence. CONCLUSIONS: These findings can be used to inform nursing
      care provided for Mexican-American mothers and their infants by assisting nurses
      to customize care to meet the cultural needs of this population.

PMID- 22469968
TI  - Making a team of experts into an expert team: October 2011.

PMID- 22469969
TI  - Synthesis of the macrolactone core of (+)-neopeltolide by transannular
      cyclization.
AB  - The synthesis of the macrolactone core of (+)-neopeltolide has been achieved. The
      key synthetic strategy involves the highly diastereoselective synthesis of the
      2,6-cis-disubstituted tetrahydropyran ring by a transannular cyclization of delta
      hydroxy alkene using mercuric trifluoroacetate. Two of the six stereocenters C-5
      and C-11 were realized from L-malic acid, while the remaining stereocenters C-3
      (Sharpless asymmetric epoxidation), C-7 (transannular cyclization), C-9
      (regioselective epoxide opening) and C-13 (chelation controlled reduction) were
      derived by asymmetric synthesis. The macrolactone ring was synthesized by
      macrocyclization using a RCM protocol.

PMID- 22469970
TI  - Magnetization reversal process at atomic scale in systems with itinerant
      electrons.
AB  - The magnetic response of itinerant electrons systems to an external magnetic
      field is investigated on the basis of a microscopic Hamiltonian from which the
      spin-polarized electronic structure is determined. The magnetic moment and grand
      thermodynamic potential of the d-electronic subsystem on a particular atomic site
      in the presence of the external field are calculated as a function of the
      moment's orientation for fixed electron configuration of its local environment.
      Self-consistent magnetic solutions strongly depend on the d-electron number,
      determined by the position of the d level relative to the Fermi energy. For
      parameters corresponding to alpha-Fe, two branches of self-consistent solutions
      with high and low magnetic moments are found. For parameters corresponding to
      bulk Cr, a Fe impurity in the Cr matrix and a Cr impurity in the Fe matrix, there
      are only low-spin solutions. The theory is also applied for describing
      magnetization reversal processes in exchange spring magnets. A slab of Fe was
      considered as a soft magnetic layer. The influence of the hard magnet is modeled
      by the inclusion of an external magnetic field applied to the interface Fe
      layers. The dependence of the hysteresis loop on the thickness of the Fe slab and
      on the value of the interface field is investigated.

PMID- 22469971
TI  - A predicted geranylgeranyl reductase reduces the omega-position isoprene of
      dolichol phosphate in the halophilic archaeon, Haloferax volcanii.
AB  - In N-glycosylation in both Eukarya and Archaea, N-linked oligosaccharides are
      assembled on dolichol phosphate prior to transfer of the glycan to the protein
      target. However, whereas only the alpha-position isoprene subunit is saturated in
      eukaryal dolichol phosphate, both the alpha- and omega-position isoprene subunits
      are reduced in the archaeal lipid. The agents responsible for dolichol phosphate
      saturation remain largely unknown. The present study sought to identify dolichol
      phosphate reductases in the halophilic archaeon, Haloferax volcanii. Homology
      based searches recognize HVO_1799 as a geranylgeranyl reductase. Mass
      spectrometry revealed that cells deleted of HVO_1799 fail to fully reduce the
      isoprene chains of H. volcanii membrane phospholipids and glycolipids. Likewise,
      the absence of HVO_1799 led to a loss of saturation of the omega-position
      isoprene subunit of C(55) and C(60) dolichol phosphate, with the effect of
      HVO_1799 deletion being more pronounced with C(60) dolichol phosphate than with
      C(55) dolichol phosphate. Glycosylation of dolichol phosphate in the deletion
      strain occurred preferentially on that version of the lipid saturated at both the
      alpha- and omega-position isoprene subunits.

PMID- 22469972
TI  - A targeted high-efficiency angiogenesis strategy as therapy for myocardial
      infarction.
AB  - AIMS: The aim of this study was to prove that an intramyocardial injection of a
      mixture of low-dose human growth factor (HGF) plasmid and microbubbles (MB) in
      combination with insonation was an effective therapy for myocardial infarction.
      MAIN METHODS: Twenty dogs with myocardial infarction were divided into 4 groups:
      (1) HGF, MB and ultrasound (HGF-US/MB), (2) HGF and US (HGF-US), (3) HGF alone
      and (4) surgery alone (control). In the HGF-US/MB group, HGF plasmid DNA (500
      MUg) mixed with 0.5 ml of MB solution was injected 5 min after coronary occlusion
      followed by insonation. With the exception of the control group, the other dogs
      were divided into two groups, one treated with the HGF gene and insonation and
      the other with the HGF gene only. KEY FINDINGS: Compared to the HGF group,
      infarct size decreased from 32%+/-7% (control) to 23%+/-5% in the HGF-US/MB group
      28 d later (P<0.05). Capillary density increased from 21.7+/-4.2/mm(2) (control)
      to 114.3+/-28.9/mm(2) in the HGF-US/MB group (P<0.01). Compared to the HGF group,
      there was a 14% decrease in the ratio of left ventricle weight/body weight and a
      25% decrease in hydroxyproline content. We also observed a 29% and 20% decrease
      in collagen volume fraction of type I and type III collagen, respectively in the
      HGF-US/MB group. SIGNIFICANCE: Intramyocardial injection of HGF and MB in
      combination with insonation enhances neovascularization and reduces ventricular
      remodeling and infarct size.

PMID- 22469973
TI  - Luteinizing hormone facilitates angiogenesis in ovarian epithelial tumor cells
      and metformin inhibits the effect through the mTOR signaling pathway.
AB  - High levels of gonadotropin are a risk factor for ovarian cancer development.
      Aberrant gonadotropin levels benefit tumor angiogenesis, but the detailed
      mechanism is not clear. Therefore, the aim of this study was to investigate the
      molecular mechanism of high levels of luteinizing hormone (LH) on the promotion
      of tumor angiogenesis and to outline a feasible therapeutic strategy. Western
      blotting and immunofluorescence staining were used to determine the effect of LH
      on VEGF and slit2 expression and examine the signaling pathway involved in
      regulating the expression of both molecules. Real-time PCR was used to
      investigate the effect of metformin on LH induction of VEGF and slit2 expression.
      It was found that 50 mIU/ml LH significantly upregulated VEGF and slit2
      expression, and activated the PI3K/AKT-mTOR signaling pathway. However, metformin
      inhibited the mTOR signaling pathway and further blocked LH-induced VEGF and
      slit2 expression. In conclusion, high levels of LH promote angiogenesis in
      ovarian cancer via the PI3K/AKT-mTOR pathway. However, metformin could inhibit
      tumor angiogenesis by blocking the mTOR signaling pathway.

PMID- 22469975
TI  - The Greatwall kinase: a new pathway in the control of the cell cycle.
AB  - New data have recently established that protein phosphorylation during mitosis is
      the result of a controlled balance between kinase and phosphatase activities and
      that, as for mitotic kinases, phosphatases are also regulated during cell
      division. This regulation is at least in part induced by the activation of the
      Greatwall (Gwl) kinase at mitotic entry. Activated Gwl phosphorylates its
      substrates cAMP-regulated phospho protein 19 (Arpp19) and alpha-endosulfine
      (ENSA), promoting their binding to and the inhibition of PP2A. Interestingly,
      besides the role of the Gwl-Arpp19/ENSA in the control of mitotic division, new
      data in yeast support the involvement of this pathway in mRNA stabilization
      during G(0) program initiation, although in this case the phosphatase PP2A
      appears not to be implicated. Finally, Gwl activity has been shown to be required
      for DNA checkpoint recovery. These new findings support the view that Gwl, Arpp19
      and ENSA could function as the core of a new signalization pathway that, by
      targeting different final substrates, could participate in a variety of
      physiological functions.

PMID- 22469974
TI  - PKCalpha phosphorylation of RhoGDI2 at Ser31 disrupts interactions with Rac1 and
      decreases GDI activity.
AB  - Rho family GTPases control a diverse range of cellular processes, and their
      deregulation has been implicated in human cancer. Guanine nucleotide dissociation
      inhibitors (GDIs) bind and sequester GTPases in the cytosol, restricting their
      actions. RhoGDI2 is a member of the GDI family that acts as a metastasis
      suppressor in a variety of cancer types; however, very little is known about the
      regulation of this protein. Here, we present a mechanism for inactivation of
      RhoGDI2 via protein kinase C (PKC) phosphorylation of Ser31 in a region that
      contacts GTPases. In cells, RhoGDI2 becomes rapidly phosphorylated at Ser31 in
      response to phorbol 12-myristate 13-acetate stimulation. Based on the effects of
      pharmacological inhibitors and knockdown by siRNA, we determine that conventional
      type PKCalpha is responsible for this phosphorylation. Phospho-mimetic S31E
      RhoGDI2 exhibits reduced binding to Rac1 relative to wild type, with a
      concomitant failure to reduce levels of activated endogenous Rac1 or remove Rac1
      from membranes. These results reveal a mechanism of downregulation of RhoGDI2
      activity through PKC-mediated phosphorylation of Ser31. We hypothesize that this
      mechanism may serve to neutralize RhoGDI2 function in tumors that express RhoGDI2
      and active PKCalpha.

PMID- 22469976
TI  - Host-related carcinoembryonic antigen cell adhesion molecule 1 promotes
      metastasis of colorectal cancer.
AB  - Liver metastasis is the predominant cause of colorectal cancer (CRC)-related
      mortality in developed countries. Carcinoembryonic antigen-related cell adhesion
      molecule 1 (CEACAM1) is a cell adhesion molecule with reduced expression in early
      phases of CRC development and thus functions as a tumor growth inhibitor.
      However, CEACAM1 is upregulated in metastatic colon cancer, suggesting a bimodal
      role in CRC progression. To investigate the role of this protein in the host
      metastatic environment, Ceacam1(-/-) mice were injected intrasplenically with
      metastatic MC38 mouse CRC cells. A significant reduction in metastatic burden was
      observed in Ceacam1(-/-) compared with wild-type (WT) livers. Intravital
      microscopy showed decreased early survival of MC38 cells in Ceacam1(-/-)
      endothelial environment. Metastatic cell proliferation within the Ceacam1(-/-)
      livers was also diminished. Bone marrow-derived cell recruitment, attenuation of
      immune infiltrates and diminished CCL2, CCL3 and CCL5 chemokine production
      participated in the reduced Ceacam1(-/-) metastatic phenotype. Transplantations
      of WT bone marrow (BM) into Ceacam1(-/-) mice fully rescued metastatic
      development, whereas Ceacam1(-/-) BM transfer into WT mice showed reduced
      metastatic burden. Chimeric immune cell profiling revealed diminished recruitment
      of CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) to Ceacam1(-/-)
      metastatic livers and adoptive transfer of MDSCs confirmed the involvement of
      these immune cells in reduction of liver metastasis. CEACAM1 may represent a
      novel metastatic CRC target for treatment.

PMID- 22469977
TI  - Mammary tumor growth and pulmonary metastasis are enhanced in a hyperlipidemic
      mouse model.
AB  - Dyslipidemia has been associated with an increased risk for developing cancer.
      However, the implicated mechanisms are largely unknown. To explore the role of
      dyslipidemia in breast cancer growth and metastasis, we used the apolipoprotein E
      (ApoE) knockout mice (ApoE(-/-)), which exhibit marked dyslipidemia, with
      elevated circulating cholesterol and triglyceride levels in the setting of normal
      glucose homeostasis and insulin sensitivity. Non-metastatic Met-1 and metastatic
      Mvt-1 mammary cancer cells derived from MMTV-PyVmT/FVB-N transgenic mice and c
      Myc/vegf tumor explants respectively, were injected into the mammary fat pad of
      ApoE(-/-) and wild-type (WT) females consuming a high-fat/high-cholesterol diet
      and tumor growth was evaluated. ApoE(-/-) mice exhibited increased tumor growth
      and displayed a greater number of spontaneous metastases to the lungs.
      Furthermore, intravenous injection of Mvt-1 cells resulted in a greater number of
      pulmonary metastases in the lungs of ApoE(-/-) mice compared with WT controls. To
      unravel the molecular mechanism involved in enhanced tumor growth in ApoE(-/-)
      mice, we studied the response of Mvt-1 cells to cholesterol in vitro. We found
      that cholesterol increased Akt(S473) phosphorylation in Mvt-1 cells as well as
      cellular proliferation, whereas cholesterol depletion in the cell membrane
      abrogated Akt(S473) phosphorylation induced by exogenously added cholesterol.
      Furthermore, in vivo administration of BKM120, a small-molecule inhibitor of
      phosphatidylinositol 3-kinase (PI3K), alleviated dyslipidemia-induced tumor
      growth and metastasis in Mvt-1 model with a concomitant decrease in PI3K/Akt
      signaling. Collectively, we suggest that the hypercholesterolemic milieu in the
      ApoE(-/-) mice is a favorable setting for mammary tumor growth and metastasis.

PMID- 22469978
TI  - CD133+ cells with cancer stem cell characteristics associates with vasculogenic
      mimicry in triple-negative breast cancer.
AB  - Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor
      cells to mimic the pattern of embryonic vasculogenic networks. In the study we
      demonstrated that CD133 expression was the highest in triple-negative (TN) breast
      cancer specimens. Importantly, VM showed statistical correlation with CD133(+)
      expression. The presence of the close relationship between VM and CD133(+)
      expression might be central for TN tumor relapse and progression. The TN breast
      cancer cell line, MDA-MB-231 cells developed a range of colony morphologies
      paralleling the holoclone, meroclone and paraclone morphologies produced by
      normal keratinocytes and other epithelial cancer cell lines when plated at clonal
      densities. Holoclone cells were capable of forming more colonies on soft agar
      than meroclone cells and paraclone cells, suggesting that holoclone cells had
      higher self-renew potential and might harbors cancer stem cells (CSCs)
      subpopulation. Strikingly, it was holoclone that displayed CD133(+) phenotype and
      formed VM. In addition, holoclone acquired endothelial cell marker vascular
      endothelial-cadherin expression and upregulated VM mediators matrix
      metalloproteinase (MMP)-2 and MMP-9 expression. The subpopulation with holoclone
      morphology, CD133(+) phenotype and CSCs characteristics might have the capacity
      of transdifferentiation and contributed to VM in TN breast cancer. The related
      molecular pathways may be used as novel therapeutic targets for the inhibition of
      angiogenesis and metastasis in TN breast carcinoma.

PMID- 22469979
TI  - Smac mimetic sensitizes glioblastoma cells to Temozolomide-induced apoptosis in a
      RIP1- and NF-kappaB-dependent manner.
AB  - Inhibitor of apoptosis (IAP) proteins are expressed at high levels in many
      cancers and therefore represent attractive targets for therapeutic intervention.
      Here, we report for the first time that the second mitochondria-derived activator
      of caspases (Smac) mimetic BV6 sensitizes glioblastoma cells toward Temozolomide
      (TMZ), the first-line chemotherapeutic agent in the treatment of glioblastoma.
      BV6 and TMZ synergistically reduce cell viability and trigger apoptosis in
      glioblastoma cells (combination index <0.4-0.8), which is accompanied by
      increased loss of mitochondrial-membrane potential, cytochrome c release, caspase
      activation and caspase-dependent apoptosis. Analysis of the molecular mechanisms
      reveals that BV6 causes rapid degradation of cIAP1, leading to stabilization of
      NF-kappaB-inducing kinase and NF-kappaB activation. BV6-stimulated NF-kappaB
      activation is critically required for sensitization toward TMZ, as inhibition of
      NF-kappaB by overexpression of the mutant IkappaBalpha super-repressor profoundly
      reduces loss of mitochondrial membrane potential, cytochrome c release, caspase
      activation and apoptosis. Of note, BV6-mediated sensitization to TMZ is not
      associated with increased tumor necrosis factor alpha (TNFalpha) production.
      Also, TNFalpha, CD95 or TRAIL-blocking antibodies or knockdown of TNFR1 have no
      or little effect on combination treatment-induced apoptosis. Interestingly, BV6
      and TMZ cooperate to trigger the formation of a RIP1 (receptor activating protein
      1)/caspase-8/FADD complex. Knockdown of RIP1 by small interfering RNA
      significantly reduces BV6- and TMZ-induced caspase-8 activation and apoptosis,
      showing that RIP1 is necessary for apoptosis induction. By demonstrating that BV6
      primes glioblastoma cells for TMZ in a NF-kappaB- and RIP1-dependent manner,
      these findings build the rationale for further (pre)clinical development of Smac
      mimetics in combination with TMZ.

PMID- 22469980
TI  - Death inducer-obliterator 1 (Dido1) is a BMP target gene and promotes BMP-induced
      melanoma progression.
AB  - Bone morphogenetic proteins (BMPs) are known to play an important role in
      melanoma development and progression. However, the downstream targets of BMPs
      have not been investigated thus far. Therefore, we treated melanoma cell lines
      with the Smad-specific BMP inhibitor Dorsomorphin and performed a cDNA
      microarray. We identified death inducer-obliterator 1 (Dido1) as a BMP-specific
      Smad-regulated target gene, which was confirmed by qRT-PCR, immunofluorescence
      staining and electrophoretic mobility shift assay experiments. An analysis of
      Dido1 expression revealed an upregulation of Dido1 levels in melanoma cell lines
      and tissues compared with normal melanocytes. Colony-formation assays showed that
      siDido1-transfected cells formed significantly smaller colonies when grown in
      soft agar compared with control cells. In addition, fluorescence-activated cell
      sorting and western blot experiments revealed that transfection of melanoma cells
      with Dido1 small interfering RNAs led to an upregulation of apoptosis.
      Furthermore, cell migratory and invasive potentials were strongly reduced in
      siDido1-transfected cells compared with control cells. Finally, we demonstrated
      that Dido1 induces the expression of Integrin alphaV, thereby promoting the
      attachment, migration, invasion and apoptosis resistance of melanoma cells.

PMID- 22469981
TI  - In vivo and in vitro models for the therapeutic targeting of Wnt signaling using
      a Tet-ODeltaN89beta-catenin system.
AB  - Although significant progress has been made in understanding the importance of
      Wnt signaling in the initiation of colorectal cancer, less is known about
      responses that accompany the reversal of oncogenic Wnt signaling. The aim of this
      study was to analyze in vivo and in vitro responses to an 'ideal' Wnt pathway
      inhibitor as a model for the therapeutic targeting of the pathway. A tetracycline
      inducible transgenic mouse model expressing truncated beta-catenin (DeltaN89beta
      catenin) that exhibited a strong intestinal hyperplasia was analyzed during the
      removal of oncogenic beta-catenin expression both in 3D 'crypt culture' and in
      vivo. Oncogenic Wnt signaling was rapidly and completely reversed. The strongest
      inhibition of Wnt target gene expression occurred within 24 h of doxycycline
      removal at which time the target genes Ascl2, Axin2 and C-myc were downregulated
      to levels below that in the control intestine. In vitro, the small molecule Wnt
      inhibitor CCT036477 induced a response within 4 h of treatment. By 7 days
      following doxycycline withdrawal, gene expression, cell proliferation and tissue
      morphology were undistinguishable from control animals.In conclusion, these
      results demonstrate that the reversal of Wnt signaling by inhibitors should
      ideally be studied within hours of treatment. The reversible system described,
      involving medium throughput in vitro approaches and rapid in vivo responses,
      should allow the rapid advance of early stage compounds into efficacy models that
      are more usually considered later in the drug discovery pipeline.

PMID- 22469982
TI  - Role of Lefty in the anti tumor activity of human adult liver stem cells.
AB  - Recent studies demonstrated that factors derived from embryonic stem cells
      inhibit the tumorigenicity of a variety of cancer cell lines. Embryonic stem cell
      secreted Lefty, an inhibitor of Nodal-signalling pathway, was implicated in
      reprogramming cancer cells. Whether adult stem cells exhibited similar properties
      has not been explored. The aim of the present study was to investigate whether
      the conditioned medium (CM) derived from adult stem cells influence in vitro and
      in vivo tumor growth by a Nodal-dependent pathway. In particular we compared the
      anti-tumor effect of CM from human liver stem cells (HLSC) with that of bone
      marrow-derived mesenchymal stem cells (MSC). We found that HLSC-CM inhibited the
      in vitro growth and promoted apoptosis in HepG2 cells that expressed a
      deregulated Nodal pathway. The effect of HLSC-CM was related to the presence of
      Lefty A in the CM of HLSC. Silencing Lefty A in HLSC or Lefty A blockade with a
      blocking peptide abrogated the anti-proliferative and pro-apoptotic effect of
      HLSC-CM. Moreover, the administration of human recombinant Lefty A protein
      mimicked the effect of HLSC-CM indicating that Nodal pathway is critical for the
      growth of HepG2. At variance of HLSC, bone marrow-derived MSC did not express and
      release Lefty A and the MSC-CM did not exhibited an anti-tumor activity in vitro,
      but rather stimulated proliferation of HepG2. In addition, the intra-tumor
      administration of HLSC-CM was able to inhibit the in vivo growth of HepG2
      hepatoma cells implanted subcutaneously in SCID mice. At variance, HLSC-CM
      derived from Lefty A silenced HLSC was unable to inhibit tumor growth. In
      conclusion, the results of present study suggest that Lefty A may account for the
      tumor suppressive activity of HLSC as a result of an inhibition of the Nodal
      signalling pathway by a mechanism similar to that described for embryonic stem
      cells.

PMID- 22469983
TI  - Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to
      the progression of cervical cancer.
AB  - MicroRNAs (miRNAs) act as important gene regulators in human genomes and their
      aberrant expression links to many malignancies. We previously identified a
      different characteristic miRNA expression profile in cervical cancer from that in
      cervical normal tissues, including the downregulated miR-424. However, the role
      and mechanism of miR-424 in cervical cancer still remain unknown. Here, we
      focused on identifying the tumor-suppressive function and clinical significance
      of miR-424 and exploring the mechanistic relevance by characterizing its target.
      We showed a significantly decreased expression of miR-424 in 147 cervical cancer
      tissues versus 74 cervical normal tissues by performing quantitative RT-PCR. In
      147 cervical cancer tissue samples, low-level expression of miR-424 was
      positively correlated with poor tumor differentiation, advanced clinical stage,
      lymph node metastasis and other poor prognostic clinicopathological parameters.
      Further in vitro observations showed that enforced expression of miR-424
      inhibited cell growth by both enhancing apoptosis and blocking G1/S transition,
      and suppressed cell migration and invasion in two human cervical cancer cell
      lines, SiHa and CaSki, implying that miR-424 functions as a tumor suppressor in
      the progression of cervical cancer. Interestingly, overexpression of miR-424
      inhibited the expression of protein checkpoint kinase 1 (Chk1) and phosphorylated
      Chk1 (p-Chk1) at residues Ser345 and decreased the activity of luciferase
      reporter containing the 3'-untranslated region (UTR) of Chk1 with predicted miR
      424-binding site. Moreover, miR-424 expression levels were inversely correlated
      with Chk1 and p-Chk1 protein levels in both cervical cancer and normal tissues.
      Furthermore, RNAi-mediated knockdown of Chk1 decreased matrix metalloproteinase 9
      expression and phenocopied the tumor suppressive effects of miR-424 in cell
      models. Taken together, our results identify a crucial tumor suppressive role of
      miR-424 in the progression of cervical cancer at least partly via upreglating the
      expression of Chk1 and p-Chk1, and suggest that miR-424 might be a candidate of
      prognostic predictor or an anticancer therapeutic target for cervical cancer
      patients.

PMID- 22469985
TI  - Kaposi's sarcoma herpesvirus lytic replication compromises apoptotic response to
      p53 reactivation in virus-induced lymphomas.
AB  - Primary effusion lymphomas (PELs) are aggressive Kaposi's sarcoma herpesvirus
      (KSHV)-induced malignancies with median survival time <6 months post-diagnosis.
      Mutations in the TP53 gene seldom occur in PELs, suggesting that genetic
      alterations in the TP53 are not selected during PEL progression. We have reported
      that p53 reactivation by an inhibitor of the p53-MDM2 interaction, Nutlin-3,
      induces selective and massive apoptosis in PEL cells leading to efficient anti
      tumor activity in a subcutaneous xenograft model for PEL. Here, we show
      compelling anti-tumor activity of Nutlin-3 in the majority of intraperitoneal PEL
      xenografts in vivo. Interestingly, our results demonstrate that spontaneous
      induction of viral lytic replication in tumors could drastically attenuate the
      p53-dependent apoptotic response to Nutlin-3. Moreover, viral reactivation
      compromised p53-dependent apoptosis in PEL cells treated with genotoxic anti
      cancer agents doxorubicin and etoposide. We have recently demonstrated that the
      Ser/Thr kinases Pim 1 and 3 are required to trigger induction of the lytic
      replication cascade of KSHV. We have now assessed the ability of a novel Pim
      kinase inhibitor to restore the Nutlin-3-induced cytotoxicity in lytic PEL cells.
      PEL cells induced to lytic replication by phorbol esters showed 50% inhibition of
      active viral replication following treatment with the Pim kinase inhibitor.
      Importantly, co-treatment of these cells with the kinase inhibitor and Nutlin-3
      resulted in a robust restoration of the Nutlin-3-induced cell death. These
      results highlight the potential impact of activation of viral lytic replication
      on disease progression and response to treatment in KSHV-induced lymphomas.

PMID- 22469986
TI  - Rage signalling promotes intestinal tumourigenesis.
AB  - Development of colon cancer is a multistep process that is regulated by intrinsic
      and extrinsic cellular signals. Extrinsic factors include molecular patterns that
      are derived from either pathogens (PAMPs) or cellular damage (DAMPs). These
      molecules can promote tumourigenesis by activation of the innate immune system,
      but the individual contribution of ligands and their receptors remains elusive.
      The receptor for advanced glycation end products (Rage) is a pattern recognition
      receptor that binds multiple ligands derived from a damaged cell environment such
      as Hmgb1 and S100 protein. Here we show that Rage signalling has a critical role
      in sporadic development of intestinal adenomas, as Apc(Min/+) Rage(-/-) mice are
      protected against tumourigenesis.

PMID- 22469984
TI  - The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL
      AF9;Nras(G12D) acute myeloid leukemia.
AB  - The Trithorax and Polycomb groups of chromatin regulators are critical for cell
      lineage specification during normal development; functions that often become
      deregulated during tumorigenesis. As an example, oncogenic fusions of the
      Trithorax-related protein mixed lineage leukemia (MLL) can initiate aggressive
      leukemias by altering the transcriptional circuitry governing hematopoietic cell
      differentiation, a process that requires multiple epigenetic pathways to
      implement. Here we used shRNA screening to identify chromatin regulators uniquely
      required in a mouse model of MLL-fusion acute myeloid leukemia, which revealed a
      role for the Polycomb repressive complex 2 (PRC2) in maintenance of this disease.
      shRNA-mediated suppression of PRC2 subunits Eed, Suz12 or Ezh1/Ezh2 led to
      proliferation arrest and differentiation of leukemia cells, with a minimal impact
      on growth of several non-transformed hematopoietic cell lines. The requirement
      for PRC2 in leukemia is partly because of its role in direct transcriptional
      repression of genes that limit the self-renewal potential of hematopoietic cells,
      including Cdkn2a. In addition to implicating a role for PRC2 in the pathogenesis
      of MLL-fusion leukemia, our results suggest, more generally, that Trithorax and
      Polycomb group proteins can cooperate with one another to maintain aberrant
      lineage programs in cancer.

PMID- 22469987
TI  - Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma
      multiforme.
AB  - The infiltration of glioma cells into adjacent tissue is one of the major
      obstacles in the therapeutic management of malignant brain tumours, in most cases
      precluding complete surgical resection. Consequently, malignant glioma patients
      almost invariably experience tumour recurrences. Within the brain, glioma cells
      migrate rapidly either amoeboidly or mesenchymally to invade surrounding
      structures, in dependence on the extracellular environment. In addition,
      radiotherapy, frequently applied as adjuvant therapeutic modality, may enhance
      tumour cell mobility. Here, we show that the receptor tyrosine kinase Mer (MerTK)
      is overexpressed in glioblastoma multiforme (GBM) and that this is accompanied
      with increased invasive potential. MerTK expression is maintained in primary GBM
      derived tumour spheres under stem cell culture conditions but diminishes
      significantly in serum-containing cultures with concomitant downregulation of
      Nestin and Sox2. Depletion of MerTK disrupts the rounded morphology of glioma
      cells and decreases their invasive capacity. Furthermore, the expression and
      phosphorylation of myosin light chain 2 are strongly associated with MerTK
      activity, indicating that the effect of MerTK on glioma cell invasion is mediated
      by actomyosin contractility. Finally, DNA damage robustly triggers the
      upregulation and phosphorylation of MerTK, which protects cells from apoptosis.
      This effect is strongly impaired upon MerTK depletion or overexpression of an
      inactive MerTK mutant. Collectively, our data suggests that MerTK is a novel
      therapeutic target in the treatment of the malignant gliomas.

PMID- 22469988
TI  - miR-143 regulates hexokinase 2 expression in cancer cells.
AB  - Tumor cells activate pathways that facilitate and stimulate glycolysis even in
      the presence of adequate levels of oxygen in order to satisfy their continuous
      need of molecules, such as nucleotides, ATP and fatty acids, necessary to support
      their rapid proliferation. Accordingly, a variety of human tumors are
      characterized by elevated expression levels of the hexokinase 2 isoform (HK2).
      Although different molecular mechanisms, including genetic and epigenetic
      mechanisms, have been suggested to account for the altered expression of HK2 in
      tumors, the potential role of microRNAs (miRNAs) in the regulation of HK2
      expression has not been evaluated. Here, we report that miR-143 inhibits HK2
      expression via a conserved miR-143 recognition motif located in the 3'
      untranslated region (3'UTR) of HK2 mRNA. We demonstrate that miR143 inhibits HK2
      expression both in primary keratinocytes and in head and neck squamous cell
      carcinoma (HNSCC)-derived cell lines. Importantly, we found that miR-143
      inversely correlates with HK2 expression in HNSCC-derived cell lines and in
      primary tumors. We also report that the miRNA-dependent regulation of hexokinase
      expression is not limited to HK2 as miR-138 targets HK1 via a specific
      recognition motif located in its 3'UTR. All these data unveil a new miRNA
      dependent mechanism of regulation of hexokinase expression potentially important
      in the regulation of glucose metabolism of cancer cells.

PMID- 22469989
TI  - Expression of STAT3, MMP-1 and TIMP-1 in gastric cancer and correlation with
      pathological features.
AB  - The aim of this study was to investigate the mRNA and protein expression of
      STAT3, MMP-1 and TIMP-1 in gastric cancer (GC), and to explore the correlations
      between these proteins and the biological behaviors of GC. Reverse transcription
      polymerase chain reaction was employed to detect the mRNA expression of STAT3,
      MMP-1 and TIMP-1 in GC tissues (n=30), adjacent normal tissues (n=30) and
      superficial gastritis (SG) tissues (n=30). Immunohistochemistry was performed
      using the SP method to measure the protein expression of STAT3
      (unphosphorylated), MMP-1 and TIMP-1. The correlation between the pathological
      features of GC and STAT3, MMP-1 as well as TIMP-1, were evaluated. The mRNA
      expression of STAT3 in GC tissues (0.821+/-0.128) was significantly higher
      compared to that in adjacent normal tissues (0.355+/-0.100) and SG tissues
      (0.398+/-0.096) (P<0.05). The mRNA expression of MMP-1 in GC tissues (0.749+/
      0.133) was significantly increased compared to adjacent normal tissues (0.335+/
      0.106) and SG tissues (0.345+/-0.063) (P<0.05). The mRNA expression of TIMP-1 in
      GC tissues (0.386+/-0.125) was comparable to that in adjacent normal tissues
      (0.343+/-0.078) and SG tissues (0.345+/-0.061), but the mRNA expression of TIMP-1
      in GC tissues was significantly correlated with the differentiation of GC cells
      and lymph node metastasis. STAT3, MMP-1 and TIMP-1 were significantly associated
      with the differentiation of GC cells and lymph node metastasis, but not related
      to age, gender and tumor size. The positive rate of unphosphorylated STAT3
      expression was dramatically higher in GC tissues (86.7%) compared to that in
      adjacent normal tissues (16.7%) and SG tissues (10.0%) (P<0.05). The positive
      rate of MMP-1 protein expression in GC tissues (63.3%) was significantly higher
      compared to that in adjacent normal tissues (13.3%) and SG tissues (16.7%)
      (P<0.05). However, no significant difference was observed in the TIMP-1-positive
      rate among the three groups (23.3, 16.7 and 10.0%, respectively; P>0.05). STAT3
      and MMP-1 may be involved in the development and metastasis of GC, and treatment
      targeting TIMP-1 may be a promising strategy.

PMID- 22469990
TI  - Brain tax: estimating the population-level impact of environmental chemicals on
      IQ scores.

PMID- 22469991
TI  - Intestinal tuberculosis in an HIV-infected patient with advanced
      immunosuppression.

PMID- 22469992
TI  - Diagnostic accuracy of computed tomography using lower doses of radiation for
      patients with Crohn's disease.
AB  - BACKGROUND & AIMS: Magnetic resonance and ultrasonography have increasing roles
      in the initial diagnosis of Crohn's disease, but computed tomography (CT) with
      positive oral contrast agents is most frequently used to identify those with
      acute extramural complications. However, CT involves exposure of patients to
      radiation. We prospectively compared the diagnostic accuracy of low-dose CT (at a
      dose comparable to that used to obtain an abdominal radiograph) with conventional
      dose CT in patients with active Crohn's disease. METHODS: Low and conventional
      dose CT of the abdomen and pelvis were acquired from 50 patients with Crohn's
      disease, referred from an inflammatory bowel disease service (20 male; median
      age, 34 years). Acute complications of Crohn's disease were suspected. Iterative
      reconstruction was performed on all CT datasets to facilitate dose reduction.
      Three radiologists reviewed the low-dose CT images before the conventional-dose
      CT images. RESULTS: The median effective dose (interquartile range) of radiation
      for the low-dose CT was reduced by 72% from that of conventional CT: from 3.5 mSv
      (3-5.08 mSv) to 0.98 mSv (0.77-1.42 mSv) (P < .001). As expected, the quality
      indexes of the low-dose images were inferior to those of the conventional-dose
      images, but no clinically significant diagnostic findings were missed with low
      dose imaging. Follow-up CT examinations were recommended for 5 patients; 1 had a
      cervical tumor, 1 had a pancreatic lesion, and 3 had intra-abdominal abscess. In
      each case, the image obtained by low-dose CT was considered sufficient for
      diagnosis. CONCLUSIONS: Although low-dose CT images are of lower quality than
      images obtained with conventional doses of radiation, no clinically significant
      diagnostic findings were missed from low-dose CT images of patients with Crohn's
      disease. The low-dose CT was obtained at a median effective dose equivalent to
      1.4 abdominal radiographs.

PMID- 22469993
TI  - Anticoagulation for cirrhotic portal vein thrombosis: bold, brave, and possibly
      beneficial.

PMID- 22469994
TI  - Optimizing SHIELD-HIT for carbon ion treatment.
AB  - The SHIELD-HIT Monte Carlo transport code has been widely used in particle
      therapy, but has previously shown some discrepancies, when compared with
      experimental data. In this work, the inelastic nuclear cross sections of SHIELD
      HIT are calibrated to experimental data for carbon ions. In addition, the models
      for nuclear fragmentation were adjusted to experiments, for the partial charge
      changing cross section of carbon ions in water. Comparison with fragmentation
      yield experiments for carbon and neon primaries were made for validation. For
      carbon primaries, excellent agreement between simulation and experiment was
      observed, with only minor discrepancies. For neon primaries, the agreement was
      also good, but larger discrepancies were observed, which require further
      investigation. In conclusion, the current version SHIELD-HIT10A is well suited
      for simulating problems arising in particle therapy for clinical ion beams.

PMID- 22469995
TI  - Valproic acid, a histone deacetylase inhibitor, enhances radiosensitivity in
      esophageal squamous cell carcinoma.
AB  - Histone deacetylase (HDAC) inhibitors have been shown to enhance radiation
      response in various cancer cell lines. Valproic acid (VPA) has been used in
      clinical practice for the treatment of epilepsy and other seizure disorders and
      is also one of the most represented HDAC inhibitors. The aim of this study was to
      evaluate the radiosensitizing ability of VPA and its mechanisms in four
      esophageal squamous cell carcinoma (ESCC) cell lines (TE9, TE10, TE11 and TE14).
      VPA inhibited the viability of all ESCC cells in a dose-dependent manner. The 50%
      inhibitory concentration (IC50) value of VPA in each cell line was between 1.02
      2.15 mM, which is higher than clinically used safe concentrations. VPA induced
      the hyperacetylation of histones H3 and H4, as well as apoptosis and had a
      radiosensitizing effect on all four ESCC cell lines at a concentration of 0.5 mM
      which is equivalent to the therapeutic plasma concentration of anti-epilepsy
      therapy in humans. The radiosensitization was accompanied by an increase in
      gammaH2AX levels, indicating the presence of double-strand breaks (DSBs), and
      decrease in Rad51 expression, a DSB repair protein. These results suggest that a
      clinically safe dose of VPA can enhance radiation-induced cytotoxicity in human
      ESCC cells by chromatin decondensation with histone hyperacetylation and
      downregulation of Rad51. In conclusion, VPA appears to be a safe and promising
      radiosensitizer for esophageal cancer radiotherapy.

PMID- 22469997
TI  - RSO Interview with Alan Jackson. Interview by Rene Michel.

PMID- 22469998
TI  - Carbon-14 bioassay for decommissioning of Hanford reactors.
AB  - The production reactors at the U.S. Department of Energy Hanford Site used large
      graphite piles as the moderator. As part of long-term decommissioning plans, the
      potential need for 14C radiobioassay of workers was identified. Technical issues
      associated with 14C bioassay and worker monitoring were investigated, including
      anticipated graphite characterization, potential intake scenarios, and the
      bioassay capabilities that may be required to support the decommissioning of the
      graphite piles. A combination of urine and feces sampling would likely be
      required for the absorption type S 14C anticipated to be encountered. However,
      the concentrations in the graphite piles appear to be sufficiently low that
      dosimetrically significant intakes of 14C are not credible, thus rendering moot
      the need for such bioassay.

PMID- 22469996
TI  - Human skeletal muscle fiber type specific protein content.
AB  - The aim of this project was to develop a method to assess fiber type specific
      protein content across the continuum of human skeletal muscle fibers. Individual
      vastus lateralis muscle fibers (n = 264) were clipped into two portions: one for
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) fiber typing
      and one for Western blot protein identification. Following fiber type
      determination, fiber segments were combined into fiber type specific pools (~20
      fibers/pool) and measured for total protein quantity, glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH), citrate synthase (CS), and total p38 content. GAPDH
      content was 64, 54, 160, and 138% more abundant in myosin heavy chain (MHC)
      I/IIa, MHC IIa, MHC IIa/IIx, and MHC IIx fibers, respectively, when compared with
      MHC I. Inversely, CS content was 528, 472, 242, and 47% more abundant in MHC I,
      MHC I/IIa, MHC IIa, and MHC IIa/IIx fibers, respectively, when compared with MHC
      IIx. Total p38 content was 87% greater in MHC IIa versus MHC I fibers. These data
      and this approach establish a reliable method for human skeletal muscle fiber
      type specific protein analysis. Initial results show that particular proteins
      exist in a hierarchal fashion throughout the continuum of human skeletal muscle
      fiber types, further highlighting the necessity of fiber type specific analysis.

PMID- 22469999
TI  - Residential radon mitigations at Kitigan Zibi Anishinabeg: comparison of above
      ground level (RIM JOIST) and above roof line discharge of radon mitigation SUB
      SLAB depressurization systems.
AB  - Radon mitigations in nine houses were conducted by installing sub-slab
      depressurization systems (SSDS) with two types of discharge and fan locations:
      Ground level discharge with the fan located in the basement or roof-discharge
      with the fan located in the attic. This paper presents a detailed comparative
      analysis of the radon reduction efficiency, condensation problems, and the cost
      effectiveness of both SSDS installation scenarios in nine houses. The mitigations
      from both SSDS scenarios were successful in reducing radon. The results of rim
      joist installations discharging above ground level with the fans located in the
      basement show that a sealed radon fan with proper fittings and sealed piping were
      able to reduce the radon to acceptable levels in a cost-effective manner.

PMID- 22470000
TI  - A method of discriminating transuranic radionuclides from radon progeny using low
      resolution alpha spectroscopy and curve-fitting techniques.
AB  - 222Rn (radon) and 220Rn (thoron) progeny are known to interfere with determining
      the presence of long-lived transuranic radionuclides, such as plutonium and
      americium, and require from several hours up to several days for conclusive
      results. Methods are proposed that should expedite the analysis of air samples
      for determining the amount of transuranic radionuclides present using low
      resolution alpha spectroscopy systems available from typical alpha continuous air
      monitors (CAMs) with multi-channel analyzer (MCA) capabilities. An alpha spectra
      simulation program was developed in Microsoft Excel visual basic that employed
      the use of Monte Carlo numerical methods and serial-decay differential equations
      that resembled actual spectra. Transuranic radionuclides were able to be
      quantified with statistical certainty by applying peak fitting equations using
      the method of least squares. Initial favorable results were achieved when samples
      containing radon progeny were decayed 15 to 30 min, and samples containing both
      radon and thoron progeny were decayed at least 60 min. The effort indicates that
      timely decisions can be made when determining transuranic activity using
      available alpha CAMs with alpha spectroscopy capabilities for counting
      retrospective air samples if accompanied by analyses that consider the
      characteristics of serial decay.

PMID- 22470001
TI  - A reevaluation of the procedures used to perform thyroid bioassay on nuclear
      medicine personnel following radioiodine handling procedures.
AB  - A routinely used thyroid uptake counter in Nuclear Medicine is evaluated to
      determine if its sensitivity is sufficient to perform routine thyroid bioassays
      on Nuclear Medicine personnel involved in handling and administering radioactive
      iodine. The BiodexAtomlab 950 (PC) Medical Spectrometer thyroid uptake counter
      system is found to be sensitive to 0.48 kBq (0.013 MUCi) for 131I, which is 31%
      of the regulatory limit of 0.04 MUCi. A computer program is developed that allows
      the Nuclear Medicine staff to perform their own thyroid counts with results
      automatically available to the Health Physics Lab via computer.

PMID- 22470002
TI  - Status of radiation protection of medical x-ray facilities in Greater Accra
      region, Ghana.
AB  - The status of radiation protection and safety of diagnostic medical x-ray
      facilities in the Greater Accra region in Ghana have been evaluated. In all, 62
      medical facilities with 86 diagnostic x-ray units were considered for the survey.
      Out of the 86 diagnostic units, there were 56 general radiograph, 13 dental
      radiography, 9 fluoroscopy, 5 computed tomography, and 3 mammography machines.
      The parameters evaluated include the tube voltage, type of film processor, and
      the required protective measures in an x-ray department. It was observed that
      none of the protective measures or equipment were fully present in the diagnostic
      units except lead aprons. The radiation protection and safety measures in the
      medical facilities need to be strengthened to protect patients, staff, and the
      general public.

PMID- 22470003
TI  - Results and lessons learned from radiological/nuclear emergency response exercise
      held in Quebec, Canada.
AB  - The Ministry of Sustainable Development, Environment and Parks of Quebec
      (Ministere du Developpement durable, de l'Environnement et des Parcs du Quebec
      MDDEP) held a 3-d provincial nuclear emergency response exercise in September
      2008 that saw participation from Canadian provincial and federal departments.
      Nuclear emergency exercises are regularly held in Quebec, given the presence of
      the Gentilly-2 nuclear power plant situated in Becancour on the St. Lawrence
      River. The significance of this exercise is that it marks the first exercise held
      in Canada where environmental samples spiked with relevant radioisotopes were
      analyzed during the exercise, both on-site and remotely, and where the results of
      those analyses had a direct impact on the decisions made during the exercise.
      Following the exercise, samples were sent to two other laboratories that are part
      of the Canadian National Nuclear Laboratory Network for analysis, providing the
      first intercomparison exercise for the Network. The results of the analysis of
      the air and drinking water samples, as well as the lessons learned during the
      exercise, are presented and discussed in this article.

PMID- 22470004
TI  - Evaluation of Ludlum Corporation's portable portal monitor and comparison with
      the HML'S existing portal monitors.
AB  - Since the Human Monitoring Laboratory compared two types of portal monitors (the
      P3 and the MiniSentry) that could be field deployed in response to an emergency,
      two more brands have been added to the inventory. This paper summarizes a
      comparison of the capabilities of the previous portal monitors with the two
      additions: the Thermo Eberline TPM-903B and the Ludlum 52-1-1. The comparison
      shows that none of the portals greatly exceed the others in capability, but that
      each will have their place during emergency deployment; however, when beta
      radiation or low energy gamma radiation is suspected, then the best choice would
      be the Ludlum 52-1-1.

PMID- 22470005
TI  - Ultrasound-guided cannula cricothyroidotomy.

PMID- 22470006
TI  - Boerhaave's syndrome: spontaneous esophageal rupture.

PMID- 22470007
TI  - Expansion of the IncX plasmid family for improved identification and typing of
      novel plasmids in drug-resistant Enterobacteriaceae.
AB  - IncX plasmids are narrow host range plasmids of Enterobactericeae that have been
      isolated for over 50years. They are known to encode type IV fimbriae enabling
      their own conjugative transfer, and to provide accessory functions to their host
      bacteria such as resistance towards antimicrobial agents and biofilm formation.
      Previous plasmid-based replicon typing procedures have indicated that the
      prevalence of IncX plasmids is low among members of the Enterobacteriaceae.
      However, examination of a number of IncX-like plasmid sequences and their
      occurrence in various organisms suggests that IncX plasmid diversity and
      prevalence is underappreciated. To address these possible shortcomings, we
      generated additional plasmid sequences of IncX plasmids of interest and compared
      them to the genomes of all sequenced IncX-like plasmids. These comparisons
      revealed that IncX plasmids possess a highly syntenic plasmid backbone, but that
      they are quite divergent with respect to nucleotide and amino acid similarity.
      Based on phylogenetic comparisons of the sequenced IncX plasmids, the IncX
      plasmid group has been expanded to include at least four subtypes, IncX1-IncX4. A
      revised IncX plasmid replicon typing procedure, based upon these sequences and
      subtypes, was then developed. Use of this revised typing procedure revealed that
      IncX plasmid occurrence among bacterial populations is much more common than had
      previously been acknowledged. Thus, this revised procedure can be used to better
      discern the occurrence of IncX type plasmids among enterobacterial populations.

PMID- 22470008
TI  - Changes, functional disorders, and diseases in the gastrointestinal tract of
      elderly.
AB  - This article describes changes in the basic digestive functions (motility,
      secretion, intraluminal digestion, absorption) that occur during aging. Elderly
      individuals frequently have oropharyngeal muscle dysmotility and altered
      swallowing of food. Reductions in esophageal peristalsis and lower esophageal
      sphincter (LES) pressures are also more common in the aged and may cause
      gastroesophageal reflux. Gastric motility and emptying and small bowel motility
      are generally normal in elderly subjects, although delayed motility and gastric
      emptying have been reported in some cases. The propulsive motility of the colon
      is also decreased, and this alteration is associated with neurological and
      endocrine-paracrine changes in the colonic wall. Decreased gastric secretions
      (acid, pepsin) and impairment of the mucous-bicarbonate barrier are frequently
      described in the elderly and may lead to gastric ulcer. Exocrine pancreatic
      secretion is often decreased, as is the bile salt content of bile. These changes
      represent the underlying mechanisms of symptomatic gastrointestinal dysfunctions
      in the elderly, such as dysphagia, gastroesophageal reflux disease, primary
      dyspepsia, irritable bowel syndrome, primary constipation, maldigestion, and
      reduced absorption of nutrients. Therapeutic management of these conditions is
      also described. The authors also review the gastrointestinal diseases that are
      more common in the elderly, such as atrophic gastritis, gastric ulcer, colon
      diverticulosis, malignant tumors, gallstones, chronic hepatitis, liver cirrhosis,
      Hepato Cellular Carcinoma (HCC), and chronic pancreatitis.

PMID- 22470009
TI  - Impact of different protein sources in the glycemic and insulinemic responses.
AB  - OBJECTIVE: The maintenance of normal blood glucose concentrations is a crucial
      factor to the achievement of a good health status throughout life. However, the
      occurrence of abnormalities in this parameter has become increasingly common,
      which can result in several non-transmissible diseases, such as type 2 diabetes
      and cardiovascular diseases. Therefore, the purpose of this study was to discuss
      the role of protein sources in the glycemic and insulinemic responses. METHODS:
      In this review paper, we critically analyzed recently published studies that
      discussed the role of different protein sources in the glycemic and insulinemic
      responses in healthy individuals and in those who have cardiovascular diseases or
      type 2 diabetes. RESULTS: The results of some of these studies suggest that the
      daily ingestion of at least one high protein meal containing low to moderate
      amounts of carbohydrate increases insulin secretion and glucose uptake, improving
      insulin sensitivity. Furthermore, the results indicate that these effects are
      particularly associated with the consumption of animal protein (p.e. hydrolyzed
      whey protein), which has a high content of branched-chain amino acids such as
      leucine, valine and others such as arginine, which leads to improvements in
      insulin secretion and uptake glucose, since it increases insulin sensitivity.
      However, there is still no consensus in the literature about the quantity and
      quality of protein capable of reducing or maintaining blood-glucose
      concentrations at the desirable range, without causing adverse effects. The
      difference in the results of the studies may be associated to methodological
      problems presented by these studies. CONCLUSIONS: Well designed studies should be
      conducted to identify the quantity and quality of protein that can lead to the
      improvement on blood glucose concentrations, without negative effects to health.
      These studies should also identify the mechanisms and the magnitude by which
      protein may affect glycemic response.

PMID- 22470010
TI  - [Neural pathophysiology of cancer anorexia].
AB  - INTRODUCTION: Approximately two thirds of cancer patients at advanced stages of
      the disease suffer from anorexia. Defined as the loss of the desire to eat,
      anorexia lower the energy intake which further exacerbates a progressive
      deterioration of the patient nutritional status. Malnutrition has a large impact
      on morbidity and mortality affecting the quality of life. Cancer anorexia
      etiology is multifactorial including complex interactions among the tumor, host
      metabolism and antineoplastic treatment. New related theories include peripheral
      and brain mechanisms affecting hypothalamic pathways; inducing behavioral and
      metabolic failure of responses to energy balance. The aim of this review is to
      describe actual concepts involved in the pathogenesis of cancer anorexia with
      special interest in brain mechanisms. CONCLUSIONS: Anorexia and reduced food
      intake are important issues in the management of cancer patients, more knowledge
      about pathogenic mechanism is needed to improve therapeutic options, prognosis
      and quality of life in cancer patients.

PMID- 22470011
TI  - [Positive effects of physical exercise on reducing the relationship between
      subcutaneous abdominal fat and morbility risk].
AB  - INTRODUCTION: The consequences related to the accumulation of abdominal fat above
      healthy levels create a considerable organic damage. Among the physiological
      consequences we can highlight heart diseases, hypertension, type-2 diabetes,
      obesity and metabolic syndrome, which drastically reduce life expectancy and
      quality. Evidence shows that health improvement is correlated to greater levels
      of physical activity. However, physical exercise can create oxidative damage on
      organs and muscular tissue, more relevant in subjects with a high percentage of
      abdominal fat. This piece of work determines which are the fundamental variables
      of the exercise program in order to optimize its advantages while minimizing
      oxidative stress. MAIN PURPOSE: To know the key variables in the accumulation of
      abdominal fat above healthy levels, and the role of exercise in prevention and
      improvement of such issue. SPECIFIC PURPOSES: 1) to identify the key variables in
      an exercise program aimed at reducing abdominal fat; 2) to understand the
      relationship between abdominal fat, health and exercise; 3) to review the latest
      research related to physical exercise and its effect on abdominal adipose tissue.
      METHODOLOGY: A search and identification of original and reviewed articles will
      be carried out in indexed impact journals within the main databases. DISCUSSION:
      Regular physical exercise, most notably aerobic one, reduces body adipose tissue
      deposits in general, and abdominal ones in particular, both in obese and
      overweight subjects.

PMID- 22470012
TI  - Burns, metabolism and nutritional requirements.
AB  - OBJECTIVES: To review the nutritional evaluation in burned patient, considering
      the literature descriptions of nutritional evaluation and energy requirements of
      these patients. INTRODUCTION: Thermal injury is the traumatic event with the
      highest metabolic response in critically ill patients. Various mathematical
      formulas have been developed to estimate nutritional requirements in burned
      patient. Indirect Calorimetry is the only method considered gold standard for
      measuring caloric expenditure. METHODS: A survey of the literature and data was
      collected based on official data bases, LILACS, EMBASE and PubMed. RESULTS: The
      metabolic changes involved in hypermetabolism are designed to supply energy to
      support immune function, brain activity, wound healing, and preservation of body
      tissues. Body weight is considered the easiest indicator and perhaps the best to
      assess the nutritional status. The most common formulas utilized in these
      patients are the Curreri, Pennisi, Schofield, Ireton-Jones, Harris-Benedict and
      the ASPEN recommendations. For children is the Mayes and World Health
      Organization formula. The majority of mathematical formulas overestimate the
      nutritional needs. The regular use of Indirect Calorimetry supplies adequate
      nutritional support to the burn patient. DISCUSSION: The traditional nutritional
      evaluation considers anthropometry, biochemical markers and estimation of
      nutritional requirements. The weight provides a basis for decisions that are
      established in the clinical context. Classic parameters can be adapted to
      intensive care environment. CONCLUSIONS: The use of Indirect Calorimetry is
      crucial to ensure the safety of the nutritional support of burn patients and this
      should be widely encouraged.

PMID- 22470013
TI  - Multidisciplinary consensus on the approach to hospital malnutrition in Spain.
AB  - RATIONALE: Disease-related malnutrition constitutes a highly prevalent healthcare
      problem with high costs associated. In Spain, the prevalence of malnutrition in
      hospitalized patients has been reported from 30% to 50%. OBJECTIVES: Main
      purposes of this consensus document were to establish recommendations that
      facilitate decision-making and action to prevent and early-diagnose disease
      related hospital malnutrition, on the management of nutritional support methods
      and actions to evaluate nutritional treatment compliance and efficacy. METHODS: A
      systematic bibliographical search of authors was performed, complemented by
      updated bibliography by author references up to 2010. From this review, some
      recommendations were defined, modified and critically evaluated by the
      representatives of scientific societies in a consensus conference (Dec 2010)
      following a structured brainstorming technique: the Metaplan((r)) technique. A
      double validation process was undertaken until final recommendations were
      obtained. RESULTS: 30 consensus recommendations for the prevention and management
      of hospital malnutrition are presented in this document. Recommendations cover
      all clinical care settings as well as prevention, screening, diagnosis, treatment
      and follow-up of disease-related malnutrition. CONCLUSIONS: Nutritional screening
      is strongly recommended at all clinical settings when nutritional risk factors
      are identified or there is clinical suspicion of malnutrition. Nutritional
      assessment should be designed and performed according to centers' resources, but
      clearly identified protocols should be available.

PMID- 22470014
TI  - Allelic frequency of G380A polymorphism of tumor necrosis factor alpha gene and
      relation with cardiovascular risk factors and adipocytokines in obese patients.
AB  - BACKGROUND: The aim of our study was to investigate the allelic frequency of the
      G308A polymorphism in the TNF alpha gene and the influence of G308A this
      polymorphism on cardiovascular risk factors and adipokine levels in obese
      patients. DESIGN: A population of 834 obesity patients was analyzed. A
      nutritional evaluation and a blood analysis were performed. The statistical
      analysis was performed for the combined G308A and A308A as mutant group and type
      G308G as wild group. RESULTS: A total of 630 patients (181 males/449 females)
      (75.5%) had the genotype G308/G308 (wild genotype group) with an average age of
      43.5 +/- 14.8 years, 188 patients (61 males/127 females) (22.5%) had the genotype
      G308/A308 (mutant genotype group-heterozygote) and 16 patients (5 males/11
      females) (1.9%) with an average age of 44.5 +/- 14.2 years had the genotype
      A308/A308 (mutant group-homorozygote) with an average age of 44.3 +/- 11.4 years,
      without statistical differences in the mean age or sex distribution. Genotypes
      G308/A308 and A308/A308 was designed (mutant genotype group) as a dominant model.
      Allelic frequency of the A substitucion -308 was 13.19%. Anthropometric,
      adipokines, insulin resistance, lipid levels ad dietary intake were similar in
      both genotypes. CONCLUSION: In conclusion, allelic frequency of G308A
      polymorphism is is in accordance with allelic frequencies observed in other
      populations. Carries of A308 allele have the same anthropometric and metabolic
      profile than wild type carriers.

PMID- 22470015
TI  - Behavioral analysis of Wistar rats fed with a flaxseed based diet added to an
      environmental enrichment.
AB  - Flaxseed has a high content of n-3 fatty acids and its intake associated with an
      environmental enrichment may promote distinct behavioral results upon habituation
      and animal behavior. This work aimed to evaluating animal behavior under the use
      of these two tools in the Open Field Test. Thirty-six male Wistar rats were
      divided into 6 groups (n = 6): FEEG, receiving chow made up of flaxseed and kept
      in enriched environment; FSEG, receiving flaxseed based diet and kept in a
      standard environment; CEEG, receiving casein based diet and kept in enriched
      environment; CSEG, receiving casein based chow and kept in standard environment;
      MCEEG, receiving chow made up of casein but modified so as to provide the same
      content of fibers and lipids found in flaxseed diet and kept in enriched
      environment; MCSEG, receiving modified casein based diet and kept in standard
      environment. All animals were kept under controlled temperature, collective cages
      and dark/light cycle, receiving chow and water ad libitum, except for MCEEG and
      MCSEG, which were pair fed with FEEG and FSEG, respectively. Chow intake and
      animal body weight were evaluated twice in a week. Animals were maintained in
      these groups from the first until the second month of life, by the time when 3
      day tests in Open Field Test began. Finishing the tests, animals were sacrificed
      and their brains were obtained in order to calculate the relative brain weight.
      Our results show an interplay between flaxseed and environmental enrichment in
      habituation to a new environment, making the animals more manageable and less
      stressed.

PMID- 22470016
TI  - [Stability of the antioxidant capacity and pH of human milk refrigerated for 72
      hours: longitudinal study].
AB  - Maternal milk is the optimal feeding way for the infant at least for the first
      six months of life. Its properties include nutrients intake and, particularly, to
      provide the infant with several beneficial compounds improving his growth and
      protecting him from the diseases typical of this time period. These properties
      justify the manipulating processes before its intake in order to promote and
      warrant the adherence to it, both at the hospital and at home, being more
      important in premature infants and/or with low birth weight given their increased
      vulnerability, is spite of the fact that during these processes some of its
      properties may be partially lost. There exist, therefore, an interest in knowing
      the impact of the procedures applied to human milk on its qualitative properties,
      such as the antioxidant capacity. OBJECTIVE: This work assesses the stability of
      the antioxidant capacity of human milk during its storage at 4o C, longitudinally
      from its extraction until 48 h of refrigeration, as well as the pH changes.
      METHOD: the milk from 30 healthy women was analyzed. The milk's antioxidant
      capacity was assessed by the following parameters: total antioxidant capacity and
      level of malondialdehyde. The results obtained showed that pH decreases gradually
      from the storage beginning, whereas the antioxidant capacity remains constant for
      the first 24 hours, with a different result depending on the parameter used, and
      thereafter significant changes were observed. CONCLUSIONS: In case of needing
      extraction and storage of maternal milk before its consumption, the storage time
      should be minimized, preferably less than 24 hours in order to preserve the
      oxidative stress.

PMID- 22470017
TI  - [Risk factors for abnormal liver function tests of parenteral nutrition in a
      referral hospital in Mexico].
AB  - INTRODUCTION: the abnormalities in liver function tests (LFTs) and liver
      complications (LC) from parenteral nutrition (PN) are common and usually
      multifactorial. These factors have not yet been assessed in the adult Mexican
      population. OBJECTIVE: To determine whether the dose prescribed > 1 g/kg is a
      risk factor for the abnormalities in liver function tests (LFTs) from PN.
      MATERIAL AND METHODS: Cohort study including patients older than 15 years and
      excluding those managed at the intensive car unit or with abnormalities in liver
      enzymes before the start of PN. The exposed and non-exposed groups were those
      receiving > 1 g of lipids per kg of body weight or < 1 g/kg, respectively. LFTs
      were defined as an increase higher than 50% of the normal range for AST, ALT, AF
      or total bilirrubin. RESULTS: the incidence of LFTs abnormalities was 20 (47.6%)
      and 15 (41.6%) in the exposed and non-exposed groups, respectively (RR 1.14 95%
      IC: 0.69-1.88; p = 0.59). The most frequent liver damage pattern was cholestatic,
      followed by the mixed pattern and then hepatocellular. The dose of prescribed
      lipids > 1 g/kg was not associated with the development of LC from LFTs
      abnormalities. The higher the dose of proteins the lower the frequency of LFTs
      abnormalities. CONCLUSION: The dose of lipids prescribed >1 g/kg was not
      associated with the development of LFTs abnormalities from PN in our sample
      population. These findings should be confirmed in clinical trials.

PMID- 22470018
TI  - Dietary intake and oxidative stress in breast cancer: before and after
      treatments.
AB  - OBJECTIVE: The aim of this study was to investigate changes in dietary intake,
      anthropometric parameters and markers of oxidative stress in 40 women who
      underwent surgery, chemotherapy or radiation therapy for breast cancer. METHODS:
      Pretreatment and post-treatment measurements included data collected through a
      food frequency questionnaire, weight and height to calculate the body mass index
      (BMI) and oxidative stress markers assessed from blood reduced glutathione (GSH),
      serum antioxidant capacity (AC), plasma thiobarbituric acid reactive substances
      (TBARS), serum lipid hydroperoxides (LH) and plasma carbonyls. Differences were
      compared using paired Student's t-test or paired Wilcoxon's test. RESULTS: A
      significant increase (P < 0.05) in the intake of the food groups: meat and eggs,
      dairy products, beans, oils and fats, as well as food from the subgroups: red
      meat, milk and other dairy products rich in fat, fruit rich in vitamin C and
      vegetable fats was found after treatments. There was a significant increase in
      body weight (P < 0.05), BMI (P < 0.05), levels of TBARS (P < 0.0001), LH (P <
      0.005) and carbonyls (P < 0.0001) and a significant decrease of levels of AC (P <
      0.005) and GSH (P < 0.0001). CONCLUSION: Breast cancer diagnosis and treatments
      were associated with dietary intake changes and increased body weight, BMI and
      oxidative stress. These potential changes have important implications for
      preventive nutrition counseling.

PMID- 22470019
TI  - Ground roasted peanuts leads to a lower post-prandial glycemic response than raw
      peanuts.
AB  - INTRODUCTION: Few studies have evaluated the effect of nuts processing on the
      glycemic response and satiety. OBJECTIVE: To evaluate the effect of peanut
      processing on glycemic response, and energy and nutrients intake. METHOD:
      Thirteen healthy subjects (4 men and 9 women), with a mean age of 28.5 +/- 10
      years, BMI 22.7 +/- 2.5 kg/m2, and body fat 23.7 +/- 5.7% participated in this
      randomized crossover clinical trial. After 10-12 h of fasting, one of the
      following types of test meals were consumed: raw peanuts with skin (RPS), roasted
      peanuts without skin, ground-roasted peanuts without skin (GRPWS) or control
      meal. The test meals had the same nutrient composition, and were consumed with
      200 ml of water in 15 minutes. Glycemic response was evaluated 2 hours after each
      meal. Energy and nutrients intake were assessed through diet records reflecting
      the habitual food intake and food consumption 24 hours after the ingestion of
      test meal. RESULT: The area under the glycemic response curve after GRPWS was
      lower (p = 0.02) the one obtained for RPS. There was no treatment effect on
      energy intake, macronutrients and fiber consumption after the test meal.
      CONCLUSION: The consumption of ground-roasted peanuts may favor the control and
      prevention of diabetes due to its reduction on postprandial glucose response.
      However, more prospective studies are needed to confirm this hypothesis.

PMID- 22470020
TI  - [To born small for gestational age may depend on the growth curve used].
AB  - INTRODUCTION AND OBJECTIVE: Population standards of intrauterine growth are
      necessary to evaluate if the newborn has grown well, if their nutritional
      conditions are appropriate and to identify groups at risk as those small for
      gestational age (SGA). Differences in the number of SGA newborns identified,
      depending on the standard applied, have been analyzed in this study. MATERIAL AND
      METHODS: Cross-sectional study conducted in 4,486 Caucasian newborns (2,361 boys
      and 2,125 girls), born between 35 and 41 weeks. Weight and length valuation was
      performed following the standard methodology. Percentage of children under the
      10(th) percentile for weight and length was calculated depending on the standard
      used (Olsen et al. 2010, Lubchenco et al. 1966, Delgado et al. 1996, Carrascosa
      et al. 2008), being diagnosed of SGA. RESULTS: Weight and length were
      significantly higher in boys than in girls at all ages. 10(th) percentile values
      defined for every gestational age are globally similar among the different
      standards and our population, with the clear exception of Lubchenco curves whose
      10(th) percentile values are even 300 g. lower for the newborns at the highest
      gestational ages. Lubchenco charts do not fit the pattern of intrauterine growth
      of our population and identify a smaller number of SGA. The percentage of SGA of
      our sample ranged between 1.7% and 14% in depending on the standard, sex and
      gestational age considered. CONCLUSION: The number of children classified as SGA
      is different according to each standard used. Lubchenco charts identify a smaller
      number of SGA than the others. The rest of curves show similar values and seem to
      be well adapted for our population. The correct identification of SGA will allow
      a better assessment of short and long-term risks of these newborns.

PMID- 22470021
TI  - [Nutrition, metabolic syndrome and morbid obesity].
AB  - INTRODUCTION: Obesity, and specifically morbid obesity (MO), is a chronic disease
      with serious health consequences related to the associated comorbidities and
      constitutes a leading risk factor for the metabolic syndrome (MS) and
      cardiovascular disease (CVD). In the present study we analyze the abnormalities
      related to MO in the plasmatic levels of nutrients (both macro and
      micronutrients). METHODS: We retrospectively evaluated data of 497 patients, 369
      women and 128 men diagnosed of MO. The average age of the patients was 40.07
      (rank: 16-62). Previous to the study anthropometric measures, blood pressure (BP)
      and plasma levels of insulin and macronutrients and micronutrients were measured.
      RESULTS: The higher body mass index (BMI) in women and the waist circumference
      (WC) in both sexes demonstrates the existence of visceral obesity. Hypertensive
      disease (HD) was found in 18.6% of men and 33.5% of women. 55.1% of the men and
      42.3% of the women had three or more criteria defining the risk of developing
      MetS. We found hyperglycemia, insulinemia and dyslipemia. We did not find protein
      malnutrition, but there were elevated values of reactive C-protein. Biochemical
      indicators of macro and micronutrients were not altered. DISCUSSION AND
      CONCLUSIONS: The high incidence of patients with HD, carriers of three or more
      criteria that defines the metabolic syndrome (SM), suggests that a very
      significant part of our patients suffered the metabolic syndrome (MS). The term
      metabolic syndrome defines the group of factors of metabolic risk of CVD, which
      is confirmed by the elevated levels of reactive C-protein. We did not find
      abnormalities in the plasmatic levels of biochemical markers of nutrients.

PMID- 22470022
TI  - Nutrient intake in 5-17-year-old African boys and girls in a rural district of
      Kenya.
AB  - OBJECTIVE: To investigate relationships between nutritional status and growth
      among a sample of schoolchildren and adolescents living in a rural district of
      Kenya. DESIGN: Cross-sectional nutritional and anthropometric survey. SETTING:
      The data are from schools in a rural district of south-western Kenya. SUBJECTS:
      Schoolchildren and adolescents aged between 5 and 17 years of age. Anthropometric
      measurements and interviews on dietary intake were carried out in 2001 and 2002
      on 1,442 subjects. RESULTS: In this African rural sample, the degree of
      malnutrition differs with age (increasing with age) and sex (more accentuated in
      males). Several correlations (P < 0.05) were observed between nutrient adequacy
      ratios and anthropometric values, particularly in males. There were no
      correlations between anthropometric characteristics and sodium or vitamin C (in
      males and females) and vitamin A or potassium (in females). CONCLUSIONS:
      Malnutrition was more evident in subjects at puberty. The diet was deficient in
      sodium, calcium and potassium. Although weight-for-age (WAZ) and BMI-for-age
      (BMIZ) did not show significant relationships with nutrients in girls, the
      anthropometric variables were significantly correlated with micronutrients and
      thiamine in boys. To develop effective intervention strategies, it is vital to
      understand both how changes in malnutrition do occur and how different factors
      influence nutrient intake. The different growth pattern of boys and girls could
      be caused by sexual differences in environmental sensitivity, access to food and
      energy expenditure.

PMID- 22470023
TI  - [Gelatinous nutritional supplements: a useful alternative in dysphagia].
AB  - The oropharingeal dysphagia is a very prevalent syndrome among the elderly, and
      even more among institutionalized individuals. Dysphagia is frequently caused by
      neurodegenerative and cerebrovascular conditions, the dementia syndrome being the
      most common of them, where the latest stages of the process are often accompanied
      by frequent swallowing problems requiring to incorporate thick foodstuffs in the
      diet of the elderly, such as the pudding. Nutritional supplements with a
      puddinglike consistency are not financed by the National Health System.
      Therefore, when they are needed, patients must either pay their full price for
      them or thicken the liquid supplements financed by the National Health System.
      This is normally done in an individualized way, through the powder thickeners in
      the market. It is a very laborious and highly changeable process regarding the
      resulting consistency, with a poor homogeneous aspect; thus, it is complicated to
      implement this method in big community dwelling. We hereby present a different
      way to use these financed supplements, this is: mixing them up with commercial
      jelly resulting in a refined product with a homogeneous texture. These
      supplements will remain stable in their composition and safe to be used within 5
      days.

PMID- 22470024
TI  - Priority issues, study designs and geographical distribution in nutrition
      journals.
AB  - INTRODUCTION: The increased number of articles published in nutrition is a
      reflection of the relevance to scientific community. The characteristics and
      quality of nutritional studies determine whether readers can obtain valid
      conclusions from them, as well as their usefulness for evidence-based strategic
      policies. OBJECTIVE: To determine the characteristics of papers published in
      nutrition journals. METHOD: Descriptive study design. We reviewed 330 original
      papers published between January-June 2007. From: American Journal of Clinical
      Nutrition (AJCN), Journal of Nutrition, European Journal Nutrition, European
      Journal of Clinical Nutrition and Public Health Nutrition. We classified them
      according to the subjects studied; risk factors, study design and country of
      origin. RESULTS: Almost half the papers studied healthy people (53.3%). The most
      frequent illness was obesity (13.9%). Food consumption is the most frequent risk
      factor (63.3%). Social factors appear exclusively only in 3.6% of the papers.
      Clinical trials were the most common analytical design (31.8%), mainly in the
      AJCN (45.6%). Cross-sectional studies were the most frequent type of
      observational design (37.9%). Ten countries produced over half of the papers
      (51.3%). The US publishes the highest number of papers (20.6%), whilst developing
      countries make only scarce contributions to scientific literature on nutrition.
      CONCLUSIONS: Most of the papers had inferential power. They generally studied
      both healthy and sick subjects, coinciding with the aims of international
      scientific policies. However, the topics covered reflect a clear bias,
      prioritizing problems pertaining to developed countries. Social determinants of
      health should also be considered, along with behavioral and biological risk
      factors.

PMID- 22470025
TI  - [Changes of the potassium ion during the fast of Ramadan: preliminary outcomes].
AB  - BACKGROUND AND AIMS: The Islamic precept of Ramadan (R), imposes on individuals
      who practice it important physiological and psychological changes due to water
      and dietary restrictions to which they are subjected during the day, over a
      month. This fact makes a singular constrat, particularly in multicultural Western
      societies, where there is no schedule adjustments in daily activities, which are
      common in predominantly Muslim countries. Among the changes, includes the
      activation of mechanisms of adaptation to the hydrosalin restriction, with
      consequences on the homeostasis of water and ion plasma. On the relevance of the
      issue and the limited knowledge of the effects of (R) on the ion balance, the aim
      of the present study is to analyze the behaviour of potassium ion for this month,
      in order to prevent some problems that may affect health. METHODOLOGY: We have
      selected 10 young Muslim healthy men, aged between 18 and 25 years who perform
      Ramadan. Then we have analyzed biochemical parameters including ions, in blood
      and urine analysis, and also plasma levels of renin and aldosterone, one week
      before R, first and fourth week of R, and one week after the fasting. RESULTS:
      During the month of R a decrease in potassium urine excretion by the morning is
      observed. The consequence of this fact is the increase of the levels in plasma
      concentration of potassium; throughout the afternoon, an increase in its
      excretion results more effective during the fourth week of R. DISCUSSION: Changes
      in the availability of Na+, HCO3- and variability of pH, in the distal tubule,
      appear to be responsible for the potassium limited excretion observed during the
      fast of Ramadan. CONCLUSION: These finding put into consideration the need of
      further studies focussing on potassium homeostasis during Ramadan in order to
      determine which factors are implicated in the raised levels of K+ observed in
      plasma.

PMID- 22470026
TI  - Impact of dietary flaxseed (linum usitatissimum) supplementation on biochemical
      profile in healthy rats.
AB  - Flaxseed has been suggested play preventive and therapeutic roles in
      cardiovascular disease. The aim of this study was to evaluate the influence of
      flaxseed-supplemented dietary in healthy rats. We used 30 rats divided in three
      groups (n = 10): Control Group (C) was fed with a casein-based chow (10% protein;
      5% fiber; 7% lipid); Flaxseed Group (F) was fed with the casein-based chow
      supplemented with 25% flaxseed (10% protein; 7% fiber; 11% lipid); Internal
      Control Group (IC) was fed with the casein-based chow plus soybean oil and fiber
      (10% protein; 7% fiber; 11% lipid). The blood was obtained by cardiac puncture
      (after 180 days) and the serum was separated for lipid profile, glucose and
      uricacid analyses by commercial kit. Although all groups fed the same amount of
      ration, F group presented low (p < 0.05) body mass than C and IC groups. Total
      cholesterol and triacylgycerol were similar between all groups. F group presented
      HDL-C (High-density lipoprotein cholesterol) increase (p < 0.05) in 47% when
      compared C group. The LDL-C (Low-density lipoprotein cholesterol), glucose and
      uric acid were reduced (p < 0.05) 22%, 78% 64%, respectively, in F compared to C
      group. All results together suggest that the supplementation with 20% o flaxseed
      might be important to prevent cardiovascular disorders.

PMID- 22470027
TI  - New technologies applied to food frequency questionnaires: a current perspective.
AB  - The food frequency questionnaires are widely used in epidemiological researches
      like dietary assessment method. Traditionally, they have been self-administered
      in paper but the use of information and communication technologies has led to
      develop Internet and computerized food frequency questionnaires. It is the
      objective of this article to offer a global perspective of the new technologies
      applied to FFQ. It will be presented the purpose of the food frequency
      questionnaire, the number of strengths of the web-based surveys versus print
      surveys and finally, a description of the manuscripts that have used web-based
      and computerized FFQ.

PMID- 22470028
TI  - [Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in
      childhood].
AB  - INTRODUCTION: Plasma citrulline is not incorporated in endogenous or exogenous
      proteins so it is a theoretical marker of villous atrophy. Our aim was to
      correlate plasma citrulline levels with severity of villous atrophy in celiac
      patients. METHODS: Observational case-control study longitudinal in children 16
      month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children
      under gluten free diet and 35 non-celiac healthy children. Plasma amino acids
      concentration is determined, expressed in MUmol/L, and so are other clinical and
      analytical data. RESULTS: No statistically significative difference found in the
      referring to BMI, age or renal function. Small increase in fecal fat in celiac
      children. Citrulline, arginine and glutamine are significantly lower in cases
      (17.7 MUmol/l, 38.7 MUmol/l, 479.6 MUmol/l respectively) than in controls (28.9
      MUmol/l, 56.2 MUmol/l, 563.7 MUmol/l). Citrulline levels are significantly lower
      in the severe degrees of atrophy than in mild ones (13.8 MUmol/l vs. 19.7
      MUmol/l, p < 0.05), not happening so with rest of amminoacids. SUMMARY:
      Postabsortive mean of plasma citrulline is a good marker of reduction in
      enterocyte mass in celiac patients with villous atrophy; secondary reduction in
      plasma arginine too. Just a small histological alteration in intestinal biopsy is
      enough to differentiate citrulline in cases and controls and besides it can be
      seen that high levels of atrophy present with lower plasma citrulline.

PMID- 22470029
TI  - [Nutritional characteristics and lifestyle in university students].
AB  - Obesity and the lifestyle characteristic of our society lead young people to
      conditions of potential cardiovascular risk. The aim of this study was to assess
      the anthropometrical situation and the lifestyle in a sample of university
      students. A full anthropometrical evaluation was undertaken, including
      bioelectric impedance analysis (BIA), in 111 students in the last year of Human
      Nutrition and Dietetics, as well as a lifestyle questionnaire (physical activity,
      alcohol and cigarette consumption). A sexual dimorphism was found in weight
      distribution according to the classification proposed by SEEDO: 6.4% of women
      presented a weight lower than the health recommendations (there no men in this
      group) whereas 27.8% of men and 6.5% of women were in the overweight range. 15.3%
      of the cases had excessive waist circumference. Fat mass by BIA was higher among
      women. On the other hand, 67% of university students stated to perform regular
      physical activity, 16.7% stated being cigarette smokers, and 55.6% stated to
      consume high-grade alcohol. To conclude, we studied a sample population of young
      and healthy subjects with, however, a significant percentage of women with body
      weight lower than the healthy standards, overweighed people, and smokers usually
      taking high-grade alcohol. These data should elicit an alert of the potential
      cardiovascular risk in the university population if action is not taken. This
      population should be included in the health promotion plans.

PMID- 22470030
TI  - [Effect of antioxidant supplementation over oxidative stress and quality of life
      in cervical cancer].
AB  - BACKGROUND: Mexico has a high rate of cervical cancer which represents an
      important public health issue. The treatment for this disease depends on the
      extension of the tumor; for the initial stages surgery is recommended, and for
      locally advanced tumors, a combination of chemotherapy and radiotherapy is used.
      All this process affects natural antioxidant consumption and Quality of Life
      (QoL). OBJECTIVE: To find out the effect that supplementation with antioxidants
      (beta-carotene, vitamin C y vitamin E) has on oxidative stress, and quality of
      life in patient diagnosed with cervical cancer during treatments with cisplatin
      and radiotherapy. MATERIALS AND METHODS: We conducted a randomized, blind
      clinical trial in women with cervical cancer whose antineoplasic treatment was
      radiotherapy in and radiotherapy with cisplatin. Patients were randomly assigned
      to receive antioxidant therapy or a placebo. Plasma concentrations of
      malondialdehyde (MDA), free carbonyls, dityrosines, and carbonyl/protein rate in
      two different moments, before oncologic therapy, and after finishing oncology
      treatment, we also evaluated food consumption by using a validated food frequency
      questionnaire and a QOL questionnaire before treatment and after it was over. The
      effect of the antioxidant treatment was assessed by the use t-student test for
      independent and paired samples, as well as frequencies and X2 for categorical
      variables. RESULTS: We evaluated 103 patients who were randomly assigned to
      receive treatment with antioxidants 49 (47.60%) and placebo 54 (52.40%). We did
      not find statistically significant differences in food or antioxidant consumption
      according to the food frequency questionnaires. Most of the patients consumed
      more energy than needed to meet their requirement, but they did not consume
      enough of most of the antioxidants according to the Recommended Dailiy Allowance
      (RDA) recommendation. Serum levels of plasma free carbonyls and carbonil/mg of
      protein ratio were statistically significant (p < 0.009) which shows protein
      protection regarding oxidative stress in the supplemented group, this information
      was similar to the one found in the QOL questionnaire, which showed that Global
      QOL was better in the supplemented group (p < 0.025). Most of the patients had
      lower alpha-tocopherol and retinol plasma levels than the recommended values.
      CONCLUSIONS: Antioxidant supplementation showed to be effective in reducing
      oxidative stress in proteins, but it did not on food ingestion, patients did not
      meet their antioxidants requirement in their diets, in spite of an excess in
      energy consumption. Antioxidant plasma levels in most of the patients were lower
      than normal. QoL score was better in the supplemented group.

PMID- 22470031
TI  - Double blind randomized clinical trial controlled by placebo with an alpha
      linoleic acid and prebiotic enriched cookie on risk cardiovascular factor in
      obese patients.
AB  - INTRODUCTION: Inulin and FOS are prebiotics with potential benefit in
      cardiovascular risk factors. Alpha linolenic acid (ALA) is the metabolic
      precursor of the long chain n-3 fatty acid eicosapentaenoic acid (20: 5n-3), this
      fatty acid has anti-inflammatory properties. The aim of our study was to evaluate
      the response of the cardiovascular risk profile in obese patients after inclusion
      in the diet of an ALA, FOS and inulin enriched-cookie. MATERIAL AND METHODS: 36
      patients were randomized in both branches: group I (inulin, FOS and ALA enriched
      cookie) Gullon SL((r)) and group II (control cookie). Previous and after 1 month
      of the treatment, a nutritional and biochemical study was realized. RESULTS: 15
      patients finished the procotol in each group. In group I, a significantly
      increase in soluble fiber (2.3 +/- 0.8 g/day vs 7.7 +/- 0.8 g/day: p < 0.05) and
      ALA (0.6 +/- 0.5 g/day vs 3.8 +/- 0.5 g/day; p < 0.05) intakes was detected. In
      this group a significant decrease of total cholesterol (238.1 +/- 45.3 mg/dl vs
      210.5 +/- 38.1 mg/dl: p < 0.05), LDL cholesterol (153.6 +/- 23.2 mg/dl vs 127.1
      +/- 27.9 mg/dl: p < 0.05) and C reactive protein (6.6 +/- 1.4 mg/dl vs 4.4+7-1.8
      mg/dl: p < 0.05) was reached in males. Anthropometric parameters did not change
      in both groups. The increase in soluble fiber and ALA dietary intakes did not
      produce any gastrointestinal adverse effect. CONCLUSION: The increase of 2 grams
      per day of inulin, 3.1 grams per day of FOS and 3.2 grams per day of alpha
      linolenic (ALA) dietary intakes from an enriched-cookie, improved total
      cholesterol, LDL cholesterol and C reactive protein levels in obese males. As far
      as we know, this is the first study that has evaluated the effect on risk factors
      of an ALA enriched cookies.

PMID- 22470032
TI  - Long-term nutritional assessment of patients with severe short bowel syndrome
      managed with home enteral nutrition and oral intake.
AB  - BACKGROUND: Parenteral nutrition (PN) is used to control the nutritional state
      after severe intestinal resections. Whenever possible, enteral nutrition (EN) is
      used to promote intestinal rehabilitation and reduce PN dependency. Our aim is to
      verify whether EN + oral intake (OI) in severe short bowel syndrome (SBS)
      surgical adult patients can maintain adequate nutritional status in the long
      term. METHODS: This longitudinal retrospective study included 10 patients
      followed for 7 post-operative years. Body mass index (BMI), percentage of
      involuntary loss of usual body weight (UWL), free fat mass (FFM), and fat mass
      (FM) composition assessed by bioelectric impedance, and laboratory tests were
      evaluated at 6, 12, 24, 36, 48, 60, 72, and 84 months after surgery. Energy and
      protein offered in HPN and at long term by HEN+ oral intake (OI), was evaluated
      at the same periods. The statistical model of generalized estimating equations
      with p < 0,05 was used. RESULTS: With long term EN + OI there was a progressive
      increase in the UWL, a decrease in BMI, FFM, and FM (p < 0,05). PN weaning was
      possible in eight patients. Infection due to central venous catheter (CVC)
      contamination was the most common complication (1.2 episodes CVC/patient/year).
      There was an increase in energy and protein intake supply provided by HEN+OI (p <
      0.05). All patients survived for at least 2 years, seven for 5 years and six for
      7 years of follow-up. CONCLUSIONS: In the long term SBS surgical adult patients
      fed with HEN+OI couldn't maintain adequate nutritional status with loss of FM and
      FFM.

PMID- 22470033
TI  - Reduction of vitamin A deficiency and anemia in pregnancy after implementing
      proposed prenatal nutritional assistance.
AB  - INTRODUCTION: Micronutrient deficiency is an unquestionable public health
      problem, specially anemia and vitamin A deficiency (VAD). This is due to the
      collective dimension of these carencies, which reflects on morbimortality rates
      in the maternal and infant group. OBJECTIVE: to evaluate the impact of a proposal
      for prenatal nutritional assistance, comparing the prevalence of anemia and VAD,
      in pre-intervention (GI) and intervention (GII) groups. METHODS: this is a
      prospective intervention study in a cohort of pregnant women. The GI group was
      made up of 225 the GII group of 208 pregnant adults and their respective
      newborns, attended a Public Maternity Ward in Rio de Janeiro, Brazil.
      Concentration of hemoglobin was used to diagnose anemia and a standardized
      interview to diagnose night blindness (XN). RESULTS AND CONCLUSION: after
      adjusting for confounding variables, through logistic regression, the protective
      effect of intervention at the onset of anemia (OR = 0.420; IC 95% = 0.251-0.702),
      with a significant reduction in prevalence, of 28.4% in the GI to 16.8% in the
      GII, also observed at the onset of XN (OR = 0.377; IC95% = 0.187- 0.759), with a
      reduction in prevalence of 18.7 % in the GI to 6.2% in the GII. Nutritional
      intervention has a beneficial effect on maternal health, reducing nutritional
      deficiencies most prevalent during pregnancy and the impact of these on the
      obstetric ailment.

PMID- 22470034
TI  - Preoperative determinants of outcomes of laparoscopic gastric bypass in the
      treatment of morbid obesity.
AB  - INTRODUCTION: Laparoscopic gastric bypass (LGBP) is the predominant technique in
      surgical treatment of morbid obesity. OBJECTIVES: To evaluate the results of LGBP
      and measure the validity of some hypothetical variables as predictors of these
      outcomes. METHODS: We carried out a historical cohort study which included 50
      morbidly obese patients operated with LGBP. The results were assessed by the
      Bariatric Analysis and Reporting Outcome System (BAROS), which measures the
      following parameters: the percentage of excess weight loss (EWL), changes in co
      morbidities, quality of life and complications. The independent variables were
      age, body mass index (BMI), sex, history of depression and presence of more than
      one cardiovascular risk factor (CVRF). RESULTS: Following LGBP, 11% of the
      results was classified as excellent, 54% as very good, 25% as good and 9% as fair
      (median follow-up period: 17 months, 7-37). The best scores were found among
      younger patients. The EWL (mean: 55.4 +/- 16.6%) was higher in patients with
      lower BMI and with no more than one cardiovascular risk factor. We obtained rates
      of resolution of CVRF of 43.7 to 68.7%, complication rates < 10% and improvement
      of quality of life. CONCLUSIONS: We believe that, following LGBP in morbidly
      obese patients, when EWL, improvement in comorbidities and quality of life as
      well as complications are jointly assessed, the best results are obtained in
      younger patients.

PMID- 22470035
TI  - [Alopecia in women with severe and morbid obesity who undergo bariatric surgery].
AB  - INTRODUCTION: Bariatric surgery leads to a significant body weigh reduction
      although it is associated to a higher risk of presenting some nutritional
      deficiencies. A common complication, little studied and mainly related to zinc
      deficiency is alopecia. OBJECTIVES: To compare the nutritional status of zinc,
      iron, copper, selenium and protein-visceral in women with different degrees of
      hair loss at 6 months after gastric bypass or tubular gastrectomy. METHODS: The
      patients were categorized into two groups according to the degree of hair loss:
      group 1 or mild loss (n = 42) and group 2 or severe hair loss (n = 45). Zinc,
      iron, copper, and selenium, as well as the indicators of the nutritional status
      of zinc, iron, copper, and proteinvisceral were assessed before and after 6
      months of the surgery. RESULTS: In both groups there was a significant body
      weight reduction at 6 months post-surgery (-38.9% +/- 16.4%). Patients in group 1
      presented a significantly higher intake of zinc (20.6 +/- 8.1 vs. 17.1 +/- 7.7
      mg/d) and iron (39.7 +/- 35.9 vs. 23.8 +/- 21.3 mg/d.), and lower compromise in
      the nutritional status of zinc and iron than group 2. However, patients in group
      2 had lower compromise in the nutritional status of copper. There were no
      differences regarding the plasma concentrations of albumin. CONCLUSIONS: The
      patients having lower hair loss at six months after surgery had higher zinc and
      iron intake and lower compromise of the nutritional status of both minerals.

PMID- 22470036
TI  - [Compliance with current dietary recommendations and geographical variability of
      diet in women participating in 7 screening programs for breast cancer in Spain].
AB  - INTRODUCTION: A healthy diet is especially important during menopause, a period
      which increases the risk of various health problems. We analyzed the diet of
      periand postmenopausal Spanish women and the degree of compliance with current
      recommendations. MATERIAL AND METHODS: We studied 3574 women 45-68 years old who
      attended breast cancer screening programmes in 7 centres (A Coruna, Barcelona,
      Burgos, Palma de Mallorca, Pamplona, Valencia and Zaragoza). Diet information was
      collected using a food frequency questionnaire validated for the Spanish
      population. For the assessment of compliance with current guidelines we used the
      recommendations by the Spanish Society of Community Nutrition for food groups
      intake and by the Spanish Federation of Nutrition, Food and Dietetics for energy,
      vitamins and minerals intake. RESULTS: The 29% of women were obese and 42%
      overweight. The average caloric intake was 2.053 kcal (SD 480). The general
      energy profile was: 43% of the energy from the carbohydrates, 36% from fats, and
      20% from proteins. There was a low vitamin D intake in all centres of the study,
      with an overall mean intake of 2.14 mg/day. A deficit of vitamin E intake in A
      Coruna and Burgos was also detected. Intake of dairy products and vegetables was
      high in all the study centers. The consumption of fruits and vegetables was very
      heterogeneous, with high intakes observed in Mallorca and Valencia and low for
      both food groups in A Coruna. The olive oil intake was high in all centers except
      Burgos with 74.3% of the women studied below the recommended 3 servings per day.
      CONCLUSIONS: A diet with less fat and protein and a higher consumption of
      vegetables, nuts and foods rich in carbohydrate might balance the energy intake
      and improve the quality of the diet correcting the low intakes of vitamins D and
      E. These recommendations are especially important in cities far from the
      Mediterranean coast where more breaches have been detected over the current
      recommendations with a lower adherence to the Mediterranean diet.

PMID- 22470037
TI  - Blood pressure of omnivorous and semi-vegetarian postmenopausal women and their
      relationship with dietary and hair concentrations of essential and toxic metals.
AB  - OBJECTIVE: This study aims to ascertain the relationships between mineral
      consumption, hair mineral content, and blood pressure. METHODS: The study
      involved 26 postmenopausal women from enclosed religious communities, 14 were
      semi-vegetarians and 12 were omnivores. Mineral dietary assessment was performed
      using a 14-d precise weight method and Food tables. Hair mineral levels were
      measured by means Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and
      Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-OES). Multivariable
      stepwise linear regression analyses were performed to find out the variables that
      affected most blood pressure. RESULTS: In general terms, the omnivorous diet
      contained a significantly higher mineral content than the semi-vegetarian one.
      The mineral intake from both diets implied no health risk to the women studied,
      as their estimated daily intake (EDI) of toxic elements such as Cd and Pb was
      lower than their respective provisional tolerable weekly intake (PTWI) of these
      minerals. Hair of the semi-vegetarians contained higher amounts of Al (p < 0.01),
      Ba (p < 0.01), K (p < 0.001), Na (p < 0.001), Pb (p < 0.001) and Mn (p < 0.01)
      but lower levels of Ca (p < 0.05) and Zn (p < 0.05) than that of their omnivorous
      counterparts. The omnivores presented significantly higher systolic (p < 0.01)
      and diastolic (p < 0.05) pressures than the semi-vegetarians. Levels of hair Co
      (R2 = 0.328; p = 0.032) and hair K (R2 = 0.409; p = 0.014)) were explicative for
      systolic and diastolic blood pressure, respectively. CONCLUSION: Several dietary
      mineral and hair contents were higher in semi-vegetarian women suggesting that
      the hair is an important mineral excretion via contributing to maintain blood
      pressure at low levels.

PMID- 22470038
TI  - [Hormonal and inflammatory biomarkers in a group of overweight and obese women].
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to describe the hormonal and
      inflammatory status of a group of overweight/obese women. PATIENTS AND METHODS:
      The sample studied was a crosssectional cohort of women > 18 years of age, BMI >=
      25 < 40 kg/m2, prior to starting a weight control program. Data collected were:
      demographic characteristics, blood pressure, anthropometric parameters, physical
      activity data, and biochemical, hormonal and inflammatory biomarkers. RESULTS:
      The study involved 104 women with a mean age of 48.4 +/- 9 years and a BMI of
      29.8 +/- 3.5 kg/m2. Some 48% of the women studied were in menopause. Some 8.9%
      had hyperinsulinemia. The mean ghrelin value was 38.8 +/- 33.6 pg/ml; there was
      no correlation between ghrelin levels and anthropometric and biochemical
      variables. CRP, leptin, adiponectin, resistin, IL6, IL10, and PAI1 were 3.0 +/-
      2.7 mg/dl, 36.3 +/- 19.5 ng/ml, 8.3 +/- 4.5 mg/ml, 24.3 +/- 23.2 ng/ml, 51.6 +/-
      93.6 pg/ml, 10.0 +/- 34.2 pg/ml and 22.3 +/- 30.6 ng/ml, respectively. Obese
      patients had significantly higher mean values of resistin and PAI 1 than those
      who were overweight. These levels correlated significantly with anthropometric
      and biochemical variables; however, the correlations were weak. Age, menopause or
      the regular practice of physical activity had no effect on mean values.
      CONCLUSIONS: The group of women studied had altered inflammatory biomarkers in
      relation to people of normal weight. The study shows the inflammatory status of
      overweight/ obese individuals, and the values obtained may help to establish
      standard ranges for these markers.

PMID- 22470039
TI  - Validation of the Dutch Eating Behavior Questionnaire for Children (DEBQ-C) for
      use with Spanish children.
AB  - INTRODUCTION: The Dutch Eating Behaviour Questionnaire for children was developed
      by Van Strien and Oosterveld (2008) to measure three different eating behaviors
      (emotional eating, restrained eating and external eating); it is an adaptation of
      the DEBQ for adults. OBJECTIVE: The purpose of this study is to analyze the
      psychometric properties of the Dutch Eating Behavior Questionnaire for Children
      (DEBQ-C) with a Spanish sample. METHOD: The DEBQ-C was administered to 473
      children (240 boys and 233 girls), from 10 to 14 years old. The sample included a
      Clinical Overweight Group (COG; n = 81) comprising children who were receiving
      weight loss treatments, a Non Clinical Overweight Group (NCOG, n = 31) comprising
      children who were overweight but not in treatment, and a Normal Weight Group
      (NWG, n = 280). RESULTS: Results showed that the DEBQ-C had acceptable internal
      consistency (a = 0.70). Temporal stability was good for "External Eating" and
      "Restrained Eating" scales. Confirmatory factor analysis showed that the three
      factor solution had good fit indices. Furthermore, the clinical overweight
      participants scored significantly higher on "External Eating" and "Restrained
      Eating" compared to the normal weight children. CONCLUSION: The DEBQ-C proved to
      be an effective instrument for researching children's eating behaviors.

PMID- 22470040
TI  - [Obesity and its implication in breast cancer].
AB  - Obesity and breast cancer are two very frequent pathologies in the world today,
      which have a strong impact on society. Various research studies have tried
      linking the two. For this purpose, data was collected from the medical histories
      of 524 women who had been diagnosed and treated for breast cancer from January
      2009 to September 2010. The objectives of the study were to find and verify a
      possible association between the nutritional state of these women and their age
      when they were diagnosed with the tumour (p < 0.0001) as well as a statistically
      significant association (p < 0.0001) between the age of the first menstruation
      and the nutritional state of the patients. The results obtained showed that
      obesity was closely related to breast cancer.

PMID- 22470041
TI  - Hip fracture prognosis: could bioimpedance be an alternative to conventional
      nutritional assessment?
AB  - BACKGROUND: Risk-factors for mortality in hip fractures encompass nutritional
      status, nominally body mass index, but not body composition. Given the difficulty
      of anthropometric assessment in bedridden patients a prospective study with
      bioimpedance analysis was designed. METHODS: Elderly patients with hip fracture
      were consecutively recruited. Biochemical tests, primitive bioimpedance
      measurements (resistance, reactance and phase angle) and follow-up till one year
      were targeted. RESULTS: Patients (N = 69, 81.2 +/- 8.1 years old, 72.5% females)
      stayed in the hospital for 15.5 +/- 17.1 days, and 18.8% (13/69) required further
      hospitalization during the ensuing months. Mortality was 11.6% within 30 days,
      coinciding with hospital mortality, and an additional 11.6% till one year, thus
      reaching 23.2%. Anemia, hypoalbuminemia and low transferrin, along with elevated
      glucose and urea were frequent, suggesting undernutrition with metabolic
      derangements. Reactance, urea and creatinine were different in patients suffering
      both early and late demise. Resistance, white blood cell count and osteoporosis
      were risk factors for early mortality only , and anemia exclusively for late
      mortality. CONCLUSIONS: Primitive bioimpedance measurements, which had not been
      hitherto investigated , were prognostically related to early and late mortality.
      These markers of disease-related malnutrition and especially reactance should be
      further studied in patients unfit for anthropometric evaluation due to fracture
      and immobility.

PMID- 22470042
TI  - The effect of a modified meat product on nutritional status in institutionalized
      elderly people.
AB  - OBJECTIVE: To determine whether the inclusion of a new modified meat product as a
      dietary supplement has a positive influence on the nutritional status and blood
      lipid profile of institutionalized elderly subjects. METHOD: A sample population
      of elderly people living in institutions (9 men and 29 women aged 68-97 years)
      completed a crossover study with two dietary supplements. Nutritionally complete
      diets differed only in food supplementation, first, with a standard meat product
      and, subsequently, with a modified meat product. Venous blood samples were taken
      prior to each of the three phases of the study: the basal phase, during which
      participants followed their normal, controlled diet; a control phase (3 days per
      week for 3 weeks), during which the subjects' normal diet was supplemented with
      50 g of the standard product; and an experimental phase (3 days per week for 3
      weeks), when the normal diet was supplemented with 50 g of the modified product.
      RESULTS: Nutritional intervention did not influence hematological parameters or
      serum lipids. The modified meat product altered blood concentrations of urea,
      creatinine, GOT, transferrin, iron, and retinol-binding protein. CONCLUSIONS:
      Consumption of both the standard and the modified products contributes to
      maintaining the individuals' nutritional status and equalizes nutritional status
      across the study population with no effect on blood lipid profiles. Despite the
      limitations of the experiment, the introduction of dietary supplements in meat
      products significantly increased plasma iron levels in this elderly sample.

PMID- 22470043
TI  - [Glucose effect in the expression of endothelial lipase in human endothelial
      cells and in patients with diabetes mellitus type 2].
AB  - INTRODUCTION: Endothelial Lipase (EL), enzyme that modulates HDL metabolism, is
      overregulated by inflammatory-cytokines. Type 2 Diabetes (DM2) has been
      associated with a subclinical inflammation, so it has been ruled that these
      patients could have high levels of EL. The objectives of the research are to
      determine the effect of glucose in the expression of EL in culturing cells and
      evaluate the relation between the levels of EL and the metabolic control in
      patients with DM2. METHOD: During 24 hours, human endothelial cells (HUVEC) were
      stimulated with different concentrations of glucose (5.5, 25 and 50 mmol/L), the
      effect was evaluated over the expression of EL. In DM2 patients levels of EL,
      glucose and HbA1c were measured. We had a control group (8) to determine the
      levels of enzyme. EL was measured by immune transference, and the results were
      expressed by arbitrary units(AU). RESULTS: In HUVEC cells, the expression of EL
      was directly proportional extracellular glucose (p < 0.05). 24 diabetic patients
      were evaluated (15 females and 9 males) average age from 60 +/- 9,7 years old.
      The studied group showed levels of EL bigger than the control group (14911AU and
      10250, 18AU) respectively (p < 0.05). We found no relation between glucose, HbA1c
      and EL. CONCLUSION: In HUVEC cells there is a direct relation between extracell
      glucose and EL. The diabetic patients had higher levels of EL than the control
      group, but these was not related with glucose or HbA1c, these shows the existence
      of other factors that participate in the increasement of EL.

PMID- 22470044
TI  - [Chonic diarrhea and malabsorption due to common variable immunodeficiency,
      gastrectomy and giardiasis infection: a difficult nutritional management].
AB  - Gastric cancer is a frequent cause of cancer-related mortality in the world.
      Surgery is the only potentially curative therapy, although the adverse effects of
      surgery are common and considerable. Common variable immunodeficiency is in many
      cases cause of gastrointestinal system problems such as chronic diarrhea caused
      by infestation with giardia lamblia, nodular lymphoid hiperplasia ad loss of
      villi leading frequently to malapsortion and malnutrition. Nutritional
      deficiencies due to malapsorption (postgastrectomy and secondary to loss of
      villi, giardiasis and common variable inmunodeficiency) are common. We present
      the case of a patient with gastric cancer who underwent a gastrectomy with common
      variable hipogammaglobulinemia and chronic infestation by giardia lamblia, with
      serious diarrhea resistant to treatment and malabsorption.

PMID- 22470045
TI  - Alcohol intake and hormonal dysregulation of food intake: would be a path to
      contributor of obesity?

PMID- 22470046
TI  - [Collaborators that are mentioned in acknowledgements: forgetfulness and
      recognition of a noncompliance].

PMID- 22470047
TI  - Overexpression of HIF-1alpha in primary gallbladder carcinoma and its relation to
      vasculogenic mimicry and unfavourable prognosis.
AB  - As a novel mode of tumor neovascularization, vasculogenic mimicry (VM) has been
      reported to increase tumor-related mortality in many different solid tumors. In
      the present study, two established human gallbladder carcinoma (GBC) cell lines
      (highly aggressive GBC-SD and poorly aggressive SGC-996) cultured on a three
      dimensional matrix were assessed for the ability of VM channel formation under
      normoxic or hypoxic conditions. In addition, the relationship between HIF-1alpha
      gene expression and VM channel formation of GBC cells in vitro was measured using
      the small interfering RNA (siRNA) technique, western blotting and real-time
      reverse transcription (RT)-PCR analysis. Furthermore, H&E and CD31/periodic acid
      Schiff (PAS) staining were used to observe VM in GBC tissue samples.
      Additionally, all seventy-one specimens with VM and non-VM were stained for
      hypoxia inducible factor-1 alpha (HIF-1alpha) and its correlation with
      clinicopathological features and prognosis was analyzed simultaneously. We found
      that hypoxia could induce more VM channel formation and elevated HIF-1alpha
      expression in highly aggressive GBC-SD cells. HIF-1alpha siRNA efficiently
      knocked down HIF-1alpha expression and GBC VM networks under either normoxic or
      hypoxic conditions. VM was present in human primary GBC and overexpression of HIF
      1alpha was significantly correlated with depth of invasion and perineural
      involvement in the non-VM group. Moreover, VM and HIF-1alpha were independent
      factors for the overall survival of GBC patients and correlated with decreased
      survival. In conclusion, VM was present in human GBC. As a critical mediator in
      VM formation, high expression of HIF-1alpha was associated with VM and tumor
      progression in GBC patients.

PMID- 22470048
TI  - The orphan nuclear receptor Nur77 regulates hepatic cholesterol metabolism
      through the suppression of LDLR and HMGCR expression.
AB  - Disorders in cholesterol metabolism are critical in development of
      atherosclerosis and are related to acute myocardial infarction (AMI). The liver
      is one of the most important organs that balances cholesterol metabolism. In
      order to investigate whether Nur77 is capable of regulating cholesterol
      metabolism in HepG2 cells and to demonstrate the underlying mechanism, the
      downregulation and upregulation of Nur77 expression in HepG2 cells was achieved
      by the transfection of siRNA specific to Nur77 and the transfection of the
      recombinant plasmid, pcDNA3.1-Nur77, respectively. Following the downregulation
      and upregulation of Nur77 expression, changes in the total cholesterol (TCHO)
      levels in HepG2 cells were observed based on lipid overloading. Thereafter,
      changes in a series of key gene expressions related to hepatic cholesterol
      metabolism were measured at the mRNA and protein levels by RT-PCR and western
      blot analysis, respectively. The TCHO levels in the HepG2 cells were found to
      increase following the downregulation of Nur77 expression and to decrease
      following the upregulation of Nur77 expression; these results were confirmed by
      oil red O staining of the cells. As for the hepatic cholesterol metabolism genes,
      low-density lipoprotein receptor (LDLR) and HMGCoA reductase (HMGCR) levels
      increased following the downregulation of Nur77 expression and decreased
      following the upregulation of Nur77 expression. However, liver X receptor alpha
      (LXRalpha) expression did not change markedly along with that of Nur77. According
      to these findings, we conclude that Nur77 is capable of reducing hepatic
      cholesterol based on lipid overloading, and that this may be due to the decrease
      in LDLR and HMGCR levels.

PMID- 22470049
TI  - Environmental chemicals: evaluating low-dose effects.

PMID- 22470050
TI  - Malignant transformation from benign papillomatosis of the external auditory
      canal.
AB  - OBJECTIVE: Report a case of malignant transformation of benign ear canal
      papillomatosis to malignant squamous cell carcinoma (SCC) of the temporal bone.
      PATIENTS: A 73-year-old with papillomata involving the posterior and inferior
      walls of the right external auditory canal (EAC), which subsequently transformed
      into SCC. INTERVENTIONS: Radical mastoidectomy and excision of the tumor and then
      radical radiotherapy. MAIN OUTCOME MEASURES: Loco-regional disease control.
      Recovery of facial nerve function. RESULTS: Approximately 20 months post
      treatment, the patient remains disease free. No recovery of facial nerve
      function. CONCLUSION: Malignant transformation of a benign EAC papilloma to SCC
      of the temporal bone has not been reported previously. The association of human
      papillomavirus with temporal bone SCC has been reported in small number of
      studies with human papillomavirus subtypes 16 and 18 isolated in a high
      proportion of cases. With the increased availability in genotyping, the question
      over whether there should be further genetic analysis of benign lesions to assess
      their susceptibility to malignant transformation has merit.

PMID- 22470052
TI  - Importance of meta-analyses for evaluating carcinogens.

PMID- 22470051
TI  - Systemic immunity influences hearing preservation in cochlear implantation.
AB  - HYPOTHESIS: To determine whether a systemic immune response influences hearing
      thresholds and tissue response after cochlear implantation of hearing guinea
      pigs. METHODS: Guinea pigs were inoculated with sterile antigen (Keyhole limpet
      hemocyanin) 3 weeks before cochlear implantation. Pure-tone auditory brainstem
      response thresholds were performed before implantation and 1 and 4 weeks later.
      Dexamethasone phosphate 20% was adsorbed onto a hyaluronic acid
      carboxymethylcellulose sponge and was applied to the round window for 30 minutes
      before electrode insertion. Normal saline was used for controls. Cochlear
      histology was performed at 4 weeks after implantation to assess the tissue
      response to implantation. To control for the effect of keyhole limpet hemocyanin
      priming, a group of unprimed animals underwent cochlear implantation with a
      saline-soaked pledget applied to the round window. RESULTS: Keyhole limpet
      hemocyanin priming had no significant detrimental effect on thresholds without
      implantation. Thresholds were elevated after implantation across all frequencies
      tested (2-32 kHz) in primed animals but only at higher frequencies (4-32 kHz) in
      unprimed controls. In primed animals, dexamethasone treatment significantly
      reduced threshold shifts at 2 and 8 kHz. Keyhole limpet hemocyanin led to the
      more frequent observation of lymphocytes in the tissue response to the implant.
      CONCLUSION: Systemic immune activation at the time of cochlear implantation
      broadened the range of frequencies experiencing elevated thresholds after
      implantation. Local dexamethasone provides partial protection against this
      hearing loss, but the degree and extent of protection are less compared to
      previous studies with unprimed animals.

PMID- 22470053
TI  - Motor impairment evaluation for upper limb in stroke patients on the basis of a
      microsensor.
AB  - There has been an urgent need for an effective and efficient upper limb
      rehabilitation method for poststroke patients. We present a Micro-Sensor-based
      Upper Limb rehabilitation System for poststroke patients. The wearable motion
      capture units are attached to upper limb segments embedded in the fabric of
      garments. The body segment orientation relative to the reference frame is
      computed by fusion of the sensory data, and the upper limb trajectory and
      movement parameters are obtained. Using the micro-Sensor-based Upper Limb
      rehabilitation System, the clinical Active Range of Motion scale can be measured
      automatically; a set of novel quantitative measures, referred to as motor feature
      indices, are obtained to evaluate the quality of the movement. Experimental
      results show that the proposed motor feature indices reflect the real motor
      impairment status very well, providing objective measurements of a patient's
      functional recovery status in the rehabilitation process.

PMID- 22470054
TI  - Poly(amidoamine) dendrimer-mediated synthesis and stabilization of silver
      sulfonamide nanoparticles with increased antibacterial activity.
AB  - Silver sulfadiazine (AgSD) is a topical antibiotic with limited aqueous
      solubility. In this study, it was shown that poly(amido amine) (PAMAM) dendrimer
      complexes with SD (SDZ) and silver (Ag) could be used for a bottom-up approach to
      synthesize highly-soluble AgSD nanoparticles (NPs). These NPs were stabilized
      against crystal growth by electrostatic layer-by-layer (LBL) coating with various
      PAMAM dendrimers. Additionally, AgNPs can be incorporated in the dendrimer shells
      that augmented AgSD release. NP formulation in a cream base provided a topical
      drug-delivery platform with enhanced antibacterial properties against burn-wound
      infections, comprising three nanostructures i.e., nano-AgSD, AgNPs as well as
      PAMAM dendrimers, in one efficient, elegant nanosystem. FROM THE CLINICAL EDITOR:
      In this paper an elegant silver sulfadiazine-based nanoparticle complex is
      demonstrated with enhanced antibacterial properties and improved solubility for
      the treatment of burn-wound infections in a topical creme formulation.

PMID- 22470055
TI  - A novel gene expression system for detecting viable bladder cancer cells.
AB  - A novel transcriptional system was developed that can robustly enhance cancer
      specific gene expression. In the system, hTERT promoter-driven gene expression
      was enhanced by an advanced two-step transcriptional amplification (TSTA). This
      construct was used to develop a novel system for detection of bladder cancer
      cells. The current study evaluated the advanced TSTA system by examining the
      cancer-specific gene transcription in various bladder cancer cell lines. The
      system significantly enhanced cancer-specific luciferase gene expression in the
      bladder cancer cell lines in comparison to the previous expression system of one
      step or conventional TSTA. The fold gain of the enhancement was significantly
      correlated to the telomerase activity of the cell lines. A green fluorescent
      protein (GFP) gene encoding plasmid vector was constructed where hTERT promoter
      driving transcription is enhanced by the advanced TSTA to utilize the system for
      the imaging and detection of viable bladder cancer cells. The advanced TSTA-hTERT
      GFP plasmid successfully induced cancer-specific gene expression, showing robust
      GFP expression in human bladder cancer cell lines, but no visible GFP expression
      in normal bladder urothelial cells. The control GFP plasmid with a CMV promoter
      yielded GFP expression in both normal bladder cells and cancer cells. The
      advanced TSTA-hTERT-GFP plasmid allowed selective visualization of viable human
      bladder cancer cells in mixed cell culture containing 10- and 100-fold more
      normal bladder urothelial cells. These findings indicate that the advanced TSTA
      hTERT expressional system is a valuable tool for detecting viable bladder cancer
      cells. The current system can be applied for in vitro detection of bladder cancer
      cells in urine and other types of cancer cells disseminated in vivo.

PMID- 22470056
TI  - Rice carotenoid beta-ring hydroxylase CYP97A4 is involved in lutein biosynthesis.
AB  - Lutein is the most abundant plant carotenoid and plays essential roles in
      photosystem assembly and stabilization, as well as protection against
      photostress. To date, only a few lutein biosynthesis genes have been identified
      in crop plants. In this study, the rice Cyt P450 gene CYP97A4 encoding a
      carotenoid beta-ring hydroxylase was shown to be involved in lutein biosynthesis.
      The results revealed that CYP97A4 was preferentially expressed in leaf compared
      with spikelet, sheath, stalk and root, and encoded a protein localized at the
      subcellular level to the chloroplasts. Compared with the wild type, the three
      allelic mutants of CYP97A4 displayed lutein reductions of 12-24% with
      substantially increased alpha-carotene, while Chl a/b levels were unaltered. The
      increased alpha-carotene in the mutants led to greater sensitivity under high
      light stress. Similarly, reactive oxygen species (ROS) imaging of leaves treated
      with intense light showed that the mutants generally accumulated greater levels
      of ROS compared with wild-type plants, which probably caused detrimental effects
      to the plant photosystem. In conclusion, this study demonstrated the important
      role of CYP97A4 in alpha-carotene hydroxylation in rice, and knock-out of the
      gene reduced lutein and increased alpha-carotene, contributing to sensitivity to
      intense light.

PMID- 22470057
TI  - Overexpression of rubisco activase decreases the photosynthetic CO2 assimilation
      rate by reducing rubisco content in rice leaves.
AB  - The effects of overexpression of Rubisco activase on photosynthesis were studied
      in transgenic rice expressing barley or maize Rubisco activase. Immunoblot and
      SDS-PAGE analyses showed that transgenic lines from both gene constructs
      expressed the foreign Rubisco activase at high levels. The activation state of
      Rubisco in transgenic lines was slightly higher than that in non-transgenic
      plants (NT). In addition, light activation of Rubisco was significantly more
      rapid in transgenic lines compared with NT. These findings indicate that the
      overexpression of Rubisco activase can enhance Rubisco activation. However,
      despite enhanced activation of Rubisco in these transgenic plants, the CO(2)
      assimilation rate at ambient CO(2) conditions was decreased. This decrease in
      CO(2) assimilation rate was observed in both young developing and mature leaves
      independent of nitrogen nutrition. The contents of nitrogen and Chl did not
      differ significantly between transformants and NT; however, Rubisco content was
      substantially decreased in transgenic lines. There was no evidence for reduced
      transcription of RbcS or RbcL in these transgenic lines; in fact, transcript
      levels were marginally increased compared with NT. These results indicate that
      the overexpression of Rubisco activase leads to a decrease in Rubisco content,
      possibly due to post-transcriptional mechanisms.

PMID- 22470058
TI  - Arabidopsis P-protein filament formation requires both AtSEOR1 and AtSEOR2.
AB  - The structure-function relationship of proteinaceous filaments in sieve elements
      has long been a source of investigation in order to understand their role in the
      biology of the phloem. Two phloem filament proteins AtSEOR1 (At3g01680.1) and
      AtSEOR2 (At3g01670.1) in Arabidopsis have been identified that are required for
      filament formation. Immunolocalization experiments using a phloem filament
      specific monoclonal antibody in the respective T-DNA insertion mutants provided
      an initial indication that both proteins are necessary to form phloem filaments.
      To investigate the relationship between these two proteins further, green
      fluorescent protein (GFP)-AtSEO fusion proteins were expressed in Columbia wild
      type and T-DNA insertion mutants. Analysis of these mutants by confocal
      microscopy confirmed that phloem filaments could only be detected in the presence
      of both proteins, indicating that despite significant sequence homology the
      proteins are not functionally redundant. Individual phloem filament protein
      subunits of AtSEOR1 and AtSEOR2 were capable of forming homodimers, but not
      heterodimers in a yeast two-hybrid system. The absence of phloem filaments in
      phloem sieve elements did not result in gross alterations of plant phenotype or
      affect basal resistance to green peach aphid (Myzus persicae).

PMID- 22470059
TI  - Hyperspectral imaging techniques for rapid identification of Arabidopsis mutants
      with altered leaf pigment status.
AB  - The spectral reflectance signature of living organisms provides information that
      closely reflects their physiological status. Because of its high potential for
      the estimation of geomorphic biological parameters, particularly of gross
      photosynthesis of plants, two-dimensional spectroscopy, via the use of
      hyperspectral instruments, has been widely used in remote sensing applications.
      In genetics research, in contrast, the reflectance phenotype has rarely been the
      subject of quantitative analysis; its potential for illuminating the pathway
      leading from the gene to phenotype remains largely unexplored. In this study, we
      employed hyperspectral imaging techniques to identify Arabidopsis mutants with
      altered leaf pigment status. The techniques are comprised of two modes; the first
      is referred to as the 'targeted mode' and the second as the 'non-targeted mode'.
      The 'targeted' mode is aimed at visualizing individual concentrations and
      compositional parameters of leaf pigments based on reflectance indices (RIs)
      developed for Chls a and b, carotenoids and anthocyanins. The 'non-targeted' mode
      highlights differences in reflectance spectra of leaf samples relative to
      reference spectra from the wild-type leaves. Through the latter approach, three
      mutant lines with weak irregular reflectance phenotypes, that are hardly
      identifiable by simple observation, were isolated. Analysis of these and other
      mutants revealed that the RI-based targeted pigment estimation was robust at
      least against changes in trichome density, but was confounded by genetic defects
      in chloroplast photorelocation movement. Notwithstanding such a limitation, the
      techniques presented here provide rapid and high-sensitive means to identify
      genetic mechanisms that coordinate leaf pigment status with developmental stages
      and/or environmental stress conditions.

PMID- 22470060
TI  - Use of YouScope to implement systematic microscopy protocols.
AB  - Complex microscopy protocols, e.g., to dynamically track multiple signals in
      living cells under different conditions, are becoming more common. However, the
      implementation of complex protocols on modern, motorized microscopes often
      requires their reformulation into low-level machine language. This recoding is a
      time-consuming and error-prone task that often requires advanced programming
      skills. This unit describes how to use the high level, open-source microscope
      control platform YouScope to implement complex measurement protocols. Three
      protocols detail how to install and configure YouScope on a motorized microscope,
      how to use YouScope to quickly assess the quality of a sample, and how to set up
      imaging protocols for cells in a microplate. In addition to these protocols,
      descriptions are given for the use of various other tools YouScope provides to
      successfully accomplish various microscopy tasks.

PMID- 22470061
TI  - Determining in vivo phosphorylation sites using mass spectrometry.
AB  - Phosphorylation is the most studied protein post-translational modification (PTM)
      in biological systems, since it controls cell growth, proliferation, survival,
      and other processes. High-resolution/high mass accuracy mass spectrometers are
      used to identify protein phosphorylation sites due to their speed, sensitivity,
      selectivity, and throughput. The protocols described here focus on two common
      strategies: (1) identifying phosphorylation sites from individual proteins and
      small protein complexes, and (2) identifying global phosphorylation sites from
      whole-cell and tissue extracts. For the first, endogenous or epitope-tagged
      proteins are typically immunopurified from cell lysates, purified via gel
      electrophoresis or precipitation, and enzymatically digested into peptides.
      Samples can be optionally enriched for phosphopeptides using immobilized metal
      affinity chromatography (IMAC) or titanium dioxide (TiO(2)) and then analyzed by
      microcapillary liquid chromatography/tandem mass spectrometry (LC-MS/MS). Global
      phosphorylation site analyses that capture pSer/pThr/pTyr sites from biological
      sources sites are more resource and time consuming and involve digesting the
      whole-cell lysate, followed by peptide fractionation by strong cation-exchange
      chromatography, phosphopeptide enrichment by IMAC or TiO(2), and LC-MS/MS.
      Alternatively, the protein lysate can be fractionated by SDS-PAGE, followed by
      digestion, phosphopeptide enrichment, and LC-MS/MS. One can also
      immunoprecipitate only phosphotyrosine peptides using a pTyr antibody followed by
      LC-MS/MS.

PMID- 22470062
TI  - Preparation of genomic DNA from mammalian sperm.
AB  - Semen consists of spermatozoa and the seminal fluid, also called seminal plasma.
      This fluid is important for the survival of the spermatozoa, but may decrease the
      purity and thus quality of the DNA due to its fructose and protein content. In
      this protocol, spermatozoa are washed with ethanol to remove the fluid. The
      spermatozoa themselves are protected by a membrane rich in disulfide bonds, which
      impede cell lysis and thus hamper DNA isolation. To break disulfide bonds a
      strong antioxidant, such as dithiothreitol (DDT), is necessary. Similar to other
      protocols for DNA isolation from other mammalian tissues, proteinase K and SDS
      are included in the lysis reaction. After lysis of the sperm cells, the DNA is
      precipitated using ethanol and then redissolved in TE-buffer or ddH(2)O.

PMID- 22470063
TI  - Targeted metabolomics.
AB  - The metabolome is the terminal downstream product of the genome and consists of
      the total complement of all the low-molecular-weight molecules (metabolites) in a
      cell, tissue, or organism. Metabolomics aims to measure a wide breadth of small
      molecules in the context of physiological stimuli or disease states. Metabolomics
      methodologies fall into two distinct groups: untargeted metabolomics, an intended
      comprehensive analysis of all the measurable analytes in a sample including
      chemical unknowns, and targeted metabolomics, the measurement of defined groups
      of chemically characterized and biochemically annotated metabolites. The
      methodologies considered in this unit focus on the processes of conducting
      targeted metabolomics experiments, and the advantages of this general approach
      are highlighted herein. This unit outlines procedures for extracting nitrogenous
      metabolites (including amino acids), lipids, and intermediary metabolites
      (including TCA cycle oxoacids) from blood plasma. Specifically, protocols are
      described for analyzing these metabolites using targeted metabolomics experiments
      based on liquid chromatography-mass spectrometry.

PMID- 22470065
TI  - Native elongating transcript sequencing (NET-seq).
AB  - Advances in sequencing technology have led to the development of many high
      resolution methodologies that observe genomic activity and gene expression. This
      unit describes such an approach, native elongating transcript sequencing (NET
      seq), which reveals the density of RNA polymerase across the Saccharomyces
      cerevisiae genome with single-nucleotide resolution. A procedure for capturing
      nascent RNA transcripts directly from live cells through their association with
      the DNA-RNA-RNAP ternary complex is described. A protocol to create DNA libraries
      from the nascent RNA, allowing the identity and abundance of the 3' end of
      purified transcripts to be revealed by next generation sequencing, is also
      provided. By deep sequencing this DNA library, a quantitative measure of RNAP
      density with single-nucleotide precision is obtained. The quantitative nature of
      the NET-seq dataset relies on the high efficiency of many steps in the protocol.
      The steps that are most critical are described with suggestions for monitoring
      their success.

PMID- 22470064
TI  - RASL-seq for massively parallel and quantitative analysis of gene expression.
AB  - Large-scale, quantitative analysis of gene expression can be accomplished by
      microarray or RNA-seq analysis. While these methods are applicable to genome-wide
      analysis, it is often desirable to quantify expression of a more limited set of
      genes in hundreds, thousands, or even tens of thousands of biological samples.
      For example, some studies may require monitoring a sizable panel of key genes
      under many different experimental conditions, during development, or following
      treatment with a large library of small molecules, for which current genome-wide
      methods are either inefficient or cost-prohibitive. This unit presents a method
      that permits quantitative profiling of several hundred selected genes in a large
      number of samples by coupling RNA-mediated oligonucleotide Annealing, Selection,
      and Ligation with Next-Gen sequencing (RASL-seq). The method even allows direct
      analysis of RNA levels in cell lysates and is also adaptable to full automation,
      making it ideal for large-scale analysis of multiple biological pathways or
      regulatory gene networks in the context of systematic genetic or chemical genetic
      perturbations.

PMID- 22470066
TI  - A survey of target materials and orientations suitable for the production of
      coherent bremsstrahlung in megavoltage imaging.
AB  - Megavoltage imaging in image-guided radiotherapy usually suffers from the
      relatively small fraction of photons present in the energy range providing good
      soft tissue contrast, which corresponds to photon energies below 50 keV. As a
      consequence, comparatively high imaging doses are required to form low-noise
      images. Single-crystal targets can help to alleviate this problem through the
      emission of so-called coherent bremsstrahlung, amounting to a net increase in low
      energy photons if the electron beam impinging on a target is carefully aligned
      with a major symmetry axis of the underlying crystal lattice. In this work, we
      present an overview of crystal materials and directions that appeared
      particularly promising during our studies of this phenomenon, based on
      theoretical considerations. We find that, while diamond targets perform best in
      absolute terms, those transition metals that exhibit a body-centred cubic lattice
      appear as interesting alternatives.

PMID- 22470067
TI  - Triclosan-impregnated sutures to decrease surgical site infections: systematic
      review and meta-analysis of randomized trials.
AB  - OBJECTIVE: To determine the efficacy and safety of triclosan-impregnated sutures.
      BACKGROUND: Surgical-site infections (SSIs) produce considerable morbidity and
      increase health care costs. A potential strategy to decrease the rates of SSIs
      may be the use of triclosan-impregnated sutures. These have been endorsed and/or
      funded by professional and governmental bodies in numerous countries. Laboratory
      studies and nonsystematic reviews have suggested that these sutures may reduce
      SSIs but there has been no summative assessment of this intervention with regard
      to clinical efficacy and safety. Hence, a systematic review and meta-analysis of
      all randomized controlled trials (RCTs) investigating triclosan-impregnated
      sutures were conducted. METHODS: The Cochrane Central Register of Controlled
      Trials, MEDLINE, EMBASE, Pubmed databases, and trial registries were searched for
      published and unpublished RCTs. The endpoints of interest were the incidence of
      SSIs and wound breakdown. A random effects model was used and pooled estimates
      were reported as odds ratios (ORs) with the corresponding 95% confidence interval
      (CI). RESULTS: Seven RCTs encompassing a total of 836 patients were included in
      the final analysis. The studies were of moderate quality. Triclosan-impregnated
      sutures did not statistically significantly reduce the rates of SSIs (OR = 0.77;
      95% CI: 0.40-1.51; P = 0.45; I2 = 24%). There was no difference in the rates of
      wound breakdown between the 2 groups (OR = 1.07; 95% CI: 0.21-5.43; P = 0.93; I =
      44%) CONCLUSIONS: Triclosan-impregnated sutures do not decrease the rate of SSIs
      or decrease the rate of wound breakdown. Further high-quality independent studies
      within the right context are required before routine clinical use can be
      considered.

PMID- 22470068
TI  - A meta-analysis of surgical morbidity and recurrence after laparoscopic and open
      repair of primary unilateral inguinal hernia.
AB  - BACKGROUND: Laparoscopic inguinal hernia repair (LIHR), using a transabdominal
      preperitoneal (TAPP) or totally extraperitoneal (TEP) technique, is an
      alternative to conventional open inguinal hernia repair (OIHR). A consensus on
      outcomes of LIHR when compared with OIHR for primary, unilateral, inguinal hernia
      has not been reached. OBJECTIVES: Perform a meta-analysis of all randomized
      controlled trials (RCTs) comparing OIHR and LIHR for primary unilateral inguinal
      hernia. Outcomes were hernia recurrence and surgery-related morbidity. METHODS: A
      comprehensive search for published RCTs comparing LIHR with OIHR for primary,
      unilateral, and inguinal hernia was performed. Reviews of each study were
      conducted and data were extracted. Random effect methods were used to combine
      data. RESULTS: Data were retrieved from 27 RCTs describing 7161 patients. An
      increased risk in hernia recurrence existed when LIHR was compared with OIHR
      (relative risk [RR] = 2.06, 95% confidence interval [CI] = 1.26-3.37, P = 0.004).
      TAPP had equivalent recurrence (RR = 1.14, 95% CI = 0.78-1.68, P = 0.491) but TEP
      had increased recurrence of risk (RR = 3.72, 95% CI = 1.66-8.35, P = 0.001)
      relative to OIHR. LIHR was associated with greater perioperative complication
      risk than OIHR (RR = 1.22, 95% CI = 1.04-1.42, P = 0.015). TAPP (RR = 1.47, 95%
      CI = 1.18-1.84, P < 0.001) but not TEP (RR = 1.05, 95% CI = 0.85-1.30, P = 0.667)
      was associated with this increased complication risk. LIHR was associated with
      reduced risk of chronic pain (RR = 0.66, 95% CI = 0.51-0.87, P = 0.003) and
      chronic numbness (RR = 0.27, 95% CI = 0.12-0.58, P < 0.001) relative to OIHR.
      CONCLUSIONS: For primary unilateral inguinal hernia, TEP is associated with an
      increased risk of recurrence relative to OIHR but TAPP is not. TAPP is associated
      with increased risk of perioperative complications relative to OIHR. LIHR has a
      reduced risk of chronic pain and numbness relative to OIHR.

PMID- 22470069
TI  - Evaluating the feasibility of extended partial mastectomy and immediate reduction
      mammoplasty reconstruction as an alternative to mastectomy.
AB  - OBJECTIVES: To assess the efficacy of using concurrent partial mastectomy and
      reduction mammoplasty for resection of a wide range of tumor sizes and compare
      oncologic outcomes and postoperative complications on the basis of tumor size.
      BACKGROUND: Although tumor size greater than 4 cm has been considered an
      indication for undergoing a mastectomy, this dictum may not apply in women with
      breast hypertrophy, where the ratio of tumor size to breast size may still permit
      breast conservation. We wished to evaluate whether an approach combining partial
      mastectomy with reduction mammoplasty could provide a safe oncologic procedure
      with immediate breast reconstruction that could technically be applied even for
      large (>4 cm) lesions. METHODS: A retrospective review of all patients undergoing
      partial mastectomy and concurrent reduction mammoplasty performed at our
      institution from 2000 to 2009. Clinical characteristics at presentation,
      pathologic data, and follow-up data were collected and analyzed. RESULTS: Eighty
      five consecutive simultaneous partial mastectomy/reduction mammoplasty procedures
      were performed in 79 patients. Average tumor size was 2.8 cm for ductal carcinoma
      in situ (0.05-17.0 cm), 2.4 cm for invasive ductal carcinoma (IDC) (0.2-8.9 cm),
      3.5 cm for lobular carcinoma (1.6-8.0 cm), and 5.7 cm for phyllodes tumors (3.7
      7.6 cm). Twenty-five of 85 tumors (29.4%) were larger than 4 cm. Distribution for
      stage 0, I, II, III, and IV disease was 15, 12, 35, 19, and 2 tumors
      respectively, with an additional 2 phyllodes tumors. Median follow-up was 39
      months (10-130 months). Seventy-five patients (94.9%) achieved successful breast
      conservation, whereas 4 patients (5.1%) went on to completion mastectomy.
      Thirteen patients (16.4%) required 1 reexcision to achieve clear margins, and 2
      (2.5%) required multiple reexcisions. Two patients had a local recurrence during
      the follow-up period, one of whom underwent reexcision and the other underwent
      mastectomy. The overall complication rate was 14.1%, which included 4 major
      complications (4.7%) requiring an unplanned return to the operating room and need
      for hospital readmission, and 8 minor wound-related complications (9.4%). Neither
      recurrence nor complication rates were increased in patients with tumors greater
      than 4 cm when compared with tumors less than or equal to 4 cm. CONCLUSIONS: A
      partial mastectomy with concurrent reduction mammoplasty technique is a viable
      option for breast conservation even for larger tumors, combining a safe oncologic
      procedure with excellent cosmesis. A combined effort between breast surgeons and
      reconstructive surgeons has a high probability of success with low recurrence
      rates. In carefully selected patients, this approach may be preferable to
      mastecomy and breast reconstruction, particularly when postmastectomy radiation
      therapy is anticipated.

PMID- 22470070
TI  - Major complications, mortality, and resource utilization after open abdominal
      surgery: 0.9% saline compared to Plasma-Lyte.
AB  - OBJECTIVE: To assess the association of 0.9% saline use versus a calcium-free
      physiologically balanced crystalloid solution with major morbidity and clinical
      resource use after abdominal surgery. BACKGROUND: 0.9% saline, which results in a
      hyperchloremic acidosis after infusion, is frequently used to replace volume
      losses after major surgery. METHODS: An observational study using the Premier
      Perspective Comparative Database was performed to evaluate adult patients
      undergoing major open abdominal surgery who received either 0.9% saline (30,994
      patients) or a balanced crystalloid solution (926 patients) on the day of
      surgery. The primary outcome was major morbidity and secondary outcomes included
      minor complications and acidosis-related interventions. Outcomes were evaluated
      using multivariable logistic regression and propensity scoring models. RESULTS:
      For the entire cohort, the in-hospital mortality was 5.6% in the saline group and
      2.9% in the balanced group (P < 0.001). One or more major complications occurred
      in 33.7% of the saline group and 23% of the balanced group (P < 0.001). In the
      3:1 propensity-matched sample, treatment with balanced fluid was associated with
      fewer complications (odds ratio 0.79; 95% confidence interval 0.66-0.97).
      Postoperative infection (P = 0.006), renal failure requiring dialysis (P <
      0.001), blood transfusion (P < 0.001), electrolyte disturbance (P = 0.046),
      acidosis investigation (P < 0.001), and intervention (P = 0.02) were all more
      frequent in patients receiving 0.9% saline. CONCLUSIONS: Among hospitals in the
      Premier Perspective Database, the use of a calcium-free balanced crystalloid for
      replacement of fluid losses on the day of major surgery was associated with less
      postoperative morbidity than 0.9% saline.

PMID- 22470073
TI  - Primary hyperparathyroidism in MEN1 patients: a cohort study with longterm follow
      up on preferred surgical procedure and the relation with genotype.
AB  - OBJECTIVE: To identify the optimal surgical strategy for multiple endocrine
      neoplasia type 1 (MEN1)-related primary hyperparathyroidism (pHPT). To describe
      the course of postoperative hypoparathyroidism and to assess whether genotype is
      associated with persistent/recurrent pHPT. BACKGROUND: Surgery is the preferred
      treatment in MEN1-related pHPT, but the surgical procedure of choice is still
      uncertain. METHODS: This retrospective cohort study was performed at the
      Departments of Endocrinology of the University Medical Centers of Utrecht and
      Nijmegen, the Netherlands. Patients were selected from the Dutch MEN1 database,
      including all patients 16 years or older treated for MEN1 from 1990 to 2009. Data
      were collected by medical record review. RESULTS: Seventy-three patients
      underwent parathyroid surgery. Persistent/recurrent pHPT occurred in 53% after
      less than 3 parathyroids resected (<SPTX), 17% after subtotal resection (SPTX),
      and 19% after total resection with autotransplantation (TPTX). Persistent (>=6
      months) postoperative hypoparathyroidism occurred in 24% after <SPTX, 39% after
      SPTX, and 66% after TPTX. Median duration of hypoparathyroidism was 1.5 years, in
      65% successful cessation of vitamin D/calcium was possible, even after more than
      10 years. After <SPTX, patients with nonsense or frameshift mutations in exons 2,
      9, and 10 had a significantly lower risk of persistent/recurrent pHPT than
      patients with other mutations. After SPTX/TPTX persistence/recurrence did not
      differ with genotype. After SPTX/TPTX persistence/recurrence was more frequent (P
      = 0.07) in patients without bilateral transcervical thymectomy (TCT).
      CONCLUSIONS: SPTX with bilateral TCT is the procedure of choice for MEN1-related
      pHPT. Genotype seems to affect the chance of recurrence. Postoperative
      hypoparathyroidism lasting 6 months or more should not be considered permanent in
      MEN1.

PMID- 22470074
TI  - Calcimimetics versus parathyroidectomy for treatment of primary
      hyperparathyroidism: retrospective chart analysis of a prospective database.
AB  - OBJECTIVE: This study aims to determine the efficacy of calcimimetics in
      improving bone mineral density (BMD) in patients with primary hyperparathyroidism
      (pHPT) and compare those results to patients undergoing parathyroidectomy.
      BACKGROUND: Parathyroidectomy has been shown to improve BMD in pHPT, but
      calcimimetics have recently been advocated as a medical alternative to
      parathyroidectomy for pHPT. MATERIALS AND METHODS: We identified 17 patients that
      were treated with calcimimetics for pHPT. Seventeen patients with pHPT who
      underwent parathyroidectomy served as surgical controls. Serum calcium level,
      parathyroid hormone (PTH) level, and femur and spine BMD T scores were compared
      before and 1 year after therapy. RESULTS: Both groups were demographically
      matched. Calcium levels normalized in 70.6% of medically versus 100% of
      surgically treated patients (P = 0.026). PTH levels normalized in 35% of patients
      treated with calcimimetics versus 76% of surgical patients (P = 0.036). Femur BMD
      improved in 18.8% of medically treated patients versus 58.8% of surgical patients
      (P = 0.032). Spine BMD improved in 70.6% of medically treated patients versus
      82.4% of surgical patients (P = 0.69). Further analysis demonstrated that
      regardless of treatment, normalization of PTH was associated with significant
      improvement in femur (P = 0.03) and spine BMD (P < 0.001). Normalization of
      calcium without normalization of PTH did not impact BMD. CONCLUSIONS:
      Parathyroidectomy results in greater normalization of serum calcium and PTH
      levels and significantly improves cortical BMD compared to calcimimetics.
      Regardless of treatment, normalization of PTH is associated with significant
      improvement in spine and femur BMD, suggesting that the superior effects of
      surgery may be mediated by better control of PTH.

PMID- 22470075
TI  - The role of sphingosine kinase 1 in patients with severe acute pancreatitis.
AB  - OBJECTIVE: To investigate the role of sphingosine kinase 1 (SphK1)/sphingosine 1
      phosphate (S1P) signaling in inflammatory response in severe acute pancreatitis
      (SAP). BACKGROUND: SAP is an acute inflammatory process of the pancreas, which
      may lead to systemic inflammatory response syndrome and multiorgan dysfunction
      syndrome. SphK1 and its product S1P have been implicated in inflammatory response
      and various immune cell functions. However, the potential role for SphK1/S1P in
      inflammatory response in SAP is still unclear. METHODS: Twenty-two patients with
      SAP were enrolled in this study. SphK1 expression on peripheral neutrophils,
      monocytes, and lymphocytes was evaluated by flow cytometry. SphK enzymatic
      activity in neutrophils and lymphocytes was measured using a radiometric assay.
      The expression of S1P1 and S1P3 mRNA was determined by reverse transcriptase
      polymerase chain reaction (RT-PCR). The serum levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin-1 (IL-1beta), and IL-6 were measured by ELISA.
      RESULTS: The expression of SphK1 and SphK activity were markedly increased in
      peripheral immune cells in the early stage of SAP and then reduced in the
      restoration stage in the patients. Moreover, we found that the level of S1P3 mRNA
      in peripheral neutrophils and lymphocytes of SAP patients was significantly
      elevated in the early stage as compared with the healthy volunteers, and it
      reduced in the restoration period. SphK1 expression on human peripheral
      neutrophils, monocytes, and CD4(+) T lymphocytes were positively correlated with
      the APACHE (Acute Physiological and Chronic Health Evaluation) II scores in
      patients with SAP. The levels of serum proinflammatory cytokines including TNF
      alpha, IL-1beta, and IL-6 showed similar shifts with intracellular SphK1
      expression in SAP patients. CONCLUSIONS: The authors identified a link between
      the SphK1 expression on peripheral immune cells and the severity of SAP.
      Observations showed a possible immunomodulating role for SphK1/S1P signaling in
      inflammatory response in SAP, suggesting that regulation of SphK1/S1P pathway may
      represent novel targets in the treatment of SAP.

PMID- 22470076
TI  - Health-related quality of life in disease-free survivors of surgically treated
      lung cancer compared with the general population.
AB  - OBJECTIVE: We compared the health-related quality of life (HRQOL) of disease-free
      lung cancer survivors with those from the general population. BACKGROUND:
      Although clinical research usually is focused on how to better identify the lung
      patients most likely to benefit from surgery in terms of survival, few studies
      have concentrated specifically on HRQOL in disease-free lung cancer survivors
      compared with that of the general population. METHODS: We enrolled 830 disease
      free cancer survivors (median time since diagnosis, 4.11 years) who had a past
      diagnosis of lung cancer and treated with curative surgery (stage from 0 to III)
      at either of 2 hospitals between 2001 and 2006, and 1000 subjects without a
      history of cancer were selected randomly from a representative sample of general
      Korean population. Subjects filled out a questionnaire that included the European
      Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the lung
      cancer module. RESULTS: There were no clinically meaningful differences between
      the disease-free lung cancer survivors and general population in terms of any of
      the functioning subscales and most of the symptoms. However, survivors exhibited
      clinically meaningful worse dyspnea and financial problems on the EORTC QLQ-C30
      subscales and dyspnea, coughing, and pain in chest wall on the EORTC QLQ-LC13
      subscales than the general population. There was no clinically significant
      difference between the survivor groups according to the survival time. Survivors
      receiving lung resection, radiotherapy, and chemotherapy had clinically
      meaningful worse dyspnea than survivors receiving only lung resection. Lung
      cancer survivors with a respiratory or cardiologic comorbidity showed clinically
      meaningful worse social functioning, fatigue, dyspnea, and financial problems.
      CONCLUSIONS: These findings afford useful information clinicians preparing
      patients for lung cancer treatment by providing them with an understanding of the
      potential outcomes, and also for potential intervention targeting supportive care
      needs.

PMID- 22470078
TI  - Should more patients continue aspirin therapy perioperatively?: clinical impact
      of aspirin withdrawal syndrome.
AB  - OBJECTIVE: To provide an evidence-based focused review of aspirin use in the
      perioperative period along with an in-depth discussion of the considerations and
      risks associated with its preoperative withdrawal. BACKGROUND: For patients with
      established cardiovascular disease, taking aspirin is considered a critical
      therapy. The cessation of aspirin can cause a platelet rebound phenomenon and
      prothrombotic state leading to major adverse cardiovascular events. Despite the
      risks of aspirin withdrawal, which are exacerbated during the perioperative
      period, standard practice has been to stop aspirin before elective surgery for
      fear of excessive bleeding. Mounting evidence suggests that this practice should
      be abandoned. METHODS: We performed a PubMed and Medline literature search using
      the keywords aspirin, withdrawal, and perioperative. We manually reviewed
      relevant citations for inclusion. RESULTS/CONCLUSIONS: Clinicians should employ a
      patient-specific strategy for perioperative aspirin management that weighs the
      risks of stopping aspirin with those associated with its continuation. Most
      patients, especially those taking aspirin for secondary cardiovascular
      prevention, should have their aspirin continued throughout the perioperative
      period. When aspirin is held preoperatively, the aspirin withdrawal syndrome may
      significantly increase the risk of a major thromboembolic complication. For many
      operative procedures, the risk of perioperative bleeding while continuing aspirin
      is minimal, as compared with the concomitant thromboembolic risks associated with
      aspirin withdrawal. Those cases where aspirin should be stopped include patients
      undergoing intracranial, middle ear, posterior eye, intramedullary spine, and
      possibly transurethral prostatectomy surgery.

PMID- 22470077
TI  - Benchmarking outcomes in the critically injured trauma patient and the effect of
      implementing standard operating procedures.
AB  - OBJECTIVE: To determine and compare outcomes with accepted benchmarks in trauma
      care at 7 academic level I trauma centers in which patients were treated on the
      basis of a series of standard operating procedures (SOPs). BACKGROUND: Injury
      remains the leading cause of death for those younger than 45 years. This study
      describes the baseline patient characteristics and well-defined outcomes of
      persons hospitalized in the United States for severe blunt trauma. METHODS: We
      followed 1637 trauma patients from 2003 to 2009 up to 28 hospital days using SOPs
      developed at the onset of the study. An extensive database on patient and injury
      characteristics, clinical treatment, and outcomes was created. These data were
      compared with existing trauma benchmarks. RESULTS: The study patients were
      critically injured and were in shock. SOP compliance improved 10% to 40% during
      the study period. Multiple organ failure and mortality rates were 34.8% and
      16.7%, respectively. Time to recovery, defined as the time until the patient was
      free of organ failure for at least 2 consecutive days, was developed as a new
      outcome measure. There was a reduction in mortality rate in the cohort during the
      study that cannot be explained by changes in the patient population. CONCLUSIONS:
      This study provides the current benchmark and the overall positive effect of
      implementing SOPs for severely injured patients. Over the course of the study,
      there were improvements in morbidity and mortality rates and increasing
      compliance with SOPs. Mortality was surprisingly low, given the degree of injury,
      and improved over the duration of the study, which correlated with improved SOP
      compliance.

PMID- 22470079
TI  - Timing of cholecystectomy after mild biliary pancreatitis: a systematic review.
AB  - OBJECTIVES: To determine the risk of recurrent biliary events in the period after
      mild biliary pancreatitis but before interval cholecystectomy and to determine
      the safety of cholecystectomy during the index admission. BACKGROUND: Although
      current guidelines recommend performing cholecystectomy early after mild biliary
      pancreatitis, consensus on the definition of early (ie, during index admission or
      within the first weeks after hospital discharge) is lacking. METHODS: We
      performed a systematic search in PubMed, Embase, and Cochrane for studies
      published from January 1992 to July 2010. Included were cohort studies of
      patients with mild biliary pancreatitis reporting on the timing of
      cholecystectomy, number of readmissions for recurrent biliary events before
      cholecystectomy, operative complications (eg, bile duct injury, bleeding), and
      mortality. Study quality and risks of bias were assessed. RESULTS: After
      screening 2413 studies, 8 cohort studies and 1 randomized trial describing 998
      patients were included. Cholecystectomy was performed during index admission in
      483 patients (48%) without any reported readmissions. Interval cholecystectomy
      was performed in 515 patients (52%) after 40 days (median; interquartile range:
      19-58 days). Before interval cholecystectomy, 95 patients (18%) were readmitted
      for recurrent biliary events (0% vs 18%, P < 0.0001). These included recurrent
      biliary pancreatitis (n = 43, 8%), acute cholecystitis (n = 17), and biliary
      colics (n = 35). Patients who had an endoscopic retrograde
      cholangiopancreatography had fewer recurrent biliary events (10% vs 24%, P =
      0.001), especially less recurrent biliary pancreatitis (1% vs 9%). There were no
      differences in operative complications, conversion rate (7%), and mortality (0%)
      between index and interval cholecystectomy. Because baseline characteristics were
      only reported in 26% of patients, study populations could not be compared.
      CONCLUSIONS: Interval cholecystectomy after mild biliary pancreatitis is
      associated with a high risk of readmission for recurrent biliary events,
      especially recurrent biliary pancreatitis. Cholecystectomy during index admission
      for mild biliary pancreatitis appears safe, but selection bias could not be
      excluded.

PMID- 22470080
TI  - Intravenous 0.9% saline and general surgical patients: a problem, not a solution.

PMID- 22470081
TI  - Should laparoscopic colorectal surgery still be considered unsafe?

PMID- 22470082
TI  - Analytic models for comparing open and laparoscopic gastrectomy.

PMID- 22470083
TI  - T-tube in the modern era of liver transplantation with extended criteria donors
      and donors after cardiac death:  a reappraisal?

PMID- 22470085
TI  - Prognostic significance of aquaporins in human biliary tract carcinoma.
AB  - Aquaporins (AQPs) are important in controlling bile formation, however, the exact
      role of AQPs in human biliary tract carcinogenesis has not been clearly defined.
      In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically
      using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36
      bile duct carcinomas). The survival of patients with high AQP-5 expression was
      longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's
      proportional hazard model revealed that AQP-5 expression was an independent
      prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP
      5 expression correlated to small tumor size in biliary tract carcinoma patients
      (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion,
      histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated
      with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8
      expression had no association with clinicopathological factors. Among the 10
      patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the
      group of patients (n=5) with high AQP-5 expression were associated with higher
      rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In
      conclusion, the results of this study suggest that AQP-5 expression may be
      associated with prognosis and drug sensitivity in biliary tract carcinoma.

PMID- 22470086
TI  - Photo-response of a nanopore device with a single embedded ZnO nanoparticle.
AB  - The photo-response of a ZnO nanoparticle embedded in a nanopore made on a silicon
      nitride membrane is investigated. The ZnO nanoparticle is manipulated onto the
      nanopore and sandwiched between aluminum contact electrodes from both the top and
      bottom. The asymmetric device structure facilitates current-voltage rectification
      that enables photovoltaic capacity. Under illumination, the device shows open
      circuit voltage as well as short-circuit current. The fill factor is found to
      increase at low temperatures and reaches 48.6% at 100 K. The nanopore structure
      and the manipulation technique provide a solid platform for exploring the
      electrical properties of single nanoparticles.

PMID- 22470087
TI  - Mast cell chymase promotes cell proliferation and expression of certain cytokines
      in a dose-dependent manner.
AB  - Wound healing is a complex process, with various intracellular molecules and
      cytokines involved. Chymase is a chymotrypsin-like serine protease originally
      found to be a mast cell protease. In this study, to further investigate the role
      of chymase in the process of wound healing, the effects of chymase on cell
      proliferation and cytokine activation in human skin fibroblasts were determined.
      To determine cell proliferation, MTT assay was employed. The cells were harvested
      and total proteins were extracted and detected by western blotting. It was found
      that in vitro cell treatments with chymase led to dose-dependent increases of
      skin fibroblast proliferation. Moreover, the treatment of cells with chymase for
      6 h induced dose-dependent increases in the expression levels of transforming
      growth factor (TGF)-beta1 and interleukin (IL)-1beta, although higher doses (120
      ng/ml for TGF-beta1; 60 and 120 ng/ml for IL-1beta) did not facilitate the
      detected cytokine expression. In addition, treatment for longer periods of time
      (12 or 24 h) did not increase TGF-beta1 or IL-1beta expression. The results from
      our study will strongly facilitate the understanding of the roles of chymase in
      the process of wound healing.

PMID- 22470100
TI  - CYP1A1 is a target of miR-892a-mediated post-transcriptional repression.
AB  - Cytochrome P450 1A1 (CYP1A1) is a member of the cytochrome p450 enzyme family,
      which is involved in the metabolisms of carcinogenic metabolites, such as
      benzo(a)pyrene. In this study, we identified miR-892a as a negative regulator of
      CYP1A1 expression. Luciferase assays revealed a sequence in the 3'-untranslated
      region of CYP1A1 that displayed a perfect match with miR-892a, and revealed that
      this sequence was a specific miR-892a target site. The overexpression of miR-892a
      inhibited the expression of the CYP1A1 protein, and the miR-892a antagonist
      increased CYP1A1 expression. Of note, benzo(a)pyrene, a major inducer of CYP1A1
      transcription, decreased the expression of miR-892a. Moreover, the miR-892a
      induced CYP1A1 repression inhibited the benzo(a)pyrene-mediated decrease in cell
      viability. These data provide insight into the CYP1A1 regulatory network.

PMID- 22470101
TI  - Light- and transmission-electron-microscopic investigations on distribution of
      CD44, connexin 43 and actin cytoskeleton during the foreign body reaction to a
      nanoparticular hydroxyapatite in mini-pigs.
AB  - Foreign body giant cells (FBGCs) are formed by fusion of mononucleated
      macrophages during the foreign body response to a nanoparticulate hydroxyapatite
      (HA) implanted in defects of mini-pig femura. The molecular mechanisms underlying
      the formation of FBGCs are still largely obscure. Here we propose connexin 43
      (cx43) and CD44 as candidate molecules involved in the fusion process.
      Immunohistochemistry and ultrastructural immunogold labeling indicated that cx43
      is present within the ruffled border of FBGCs and is the main component of gap
      junctions formed between fusing macrophages. CD44 was strongly expressed during
      clustering and fusion of mononucleated macrophages. FBGCs adhering apically at
      the implanted HA showed CD44 reactivity only along the basolateral aspects of the
      plasma membranes, while podosome formation was observed within the sealing zone
      and ruffled border. Taken together, these findings demonstrate that cx43 and CD44
      are part of the fusion machinery responsible for the formation of FBGCs.
      Furthermore, the results of microfilament and cx43 labeling suggest a functional
      role for podosomes and hemi-channels in biomaterial degradation.

PMID- 22470102
TI  - ECM spreading behaviour on micropatterned TiO2 nanotube surfaces.
AB  - By electrochemical anodization, highly ordered nanotubular TiO(2) structures were
      formed on titanium surfaces with diameters of 15 and 100 nm. In previous work we
      showed that 15 nm tubes strongly enhanced adhesion and vitality of many cell
      types, whereas on 100 nm diameter tubes the induction of apoptosis was observed.
      In the present work we produce mixed (15 nm contrasted with 100 nm) nanotube
      microstructures that combine highly defined micro- and nanostructures using a
      photolithographic approach to achieve a direct comparison of adhesion and
      spreading of mesenchymal stem cells on different diameter nanotubes present on a
      single surface. On these coupled different nanoscale surfaces mesenchymal stem
      cell adhesion is initially favoured on 15 nm tube areas but, with time, a
      gradient in cell number and shape to the "unfavourable" regions of the substrate
      (100 nm tubes) can be observed. This can be explained by cells on the
      "favourable" 15 nm regions that strongly produce and shed extracellular matrix
      onto the "unfavourable" locations. These findings contribute to the design of
      cell guiding surfaces, but also demonstrate the need for a long-range defined
      homogeneous order when studying cell behaviour on nanostructured surfaces.

PMID- 22470103
TI  - Cognitive-enhancing activity of thymol and carvacrol in two rat models of
      dementia.
AB  - This study evaluated the efficacy of thymol and carvacrol against cognitive
      deficits induced by amyloid beta (Abeta) or scopolamine. Rats received bilateral
      intrahippocampal injections of Abeta(25-35) or intraperitoneal injections of
      scopolamine, and the effect of different doses of thymol, or carvacrol (0.5, 1,
      or 2 mg/kg) on cognitive function was determined. Animals were subjected to 5
      days of training in the Morris water maze: 4 days with an invisible platform to
      test spatial learning and the 5th day with a visible platform to test motivation
      and sensorimotor coordination. The acute toxicities of thymol and carvacrol were
      also studied. The results showed increases in escape latency and decreases in
      target quadrant entries in Abeta or scopolamine-treated groups. These impairments
      were reversed by pretraining administration of either thymol or carvacrol. The
      calculated LD50's of thymol (565.7 mg/kg) and carvacrol (471.2 mg/kg) were found
      to be much higher than their therapeutic doses (thymol 0.5 mg/kg, carvacrol 1
      mg/kg). These findings provide preliminary positive evidence for the
      effectiveness and safety of thymol and carvacrol in alleviating cognitive
      impairments caused by increased Abeta levels or cholinergic hypofunction.
      Anticholinesterase, antioxidant, and anti-inflammatory activities may be the
      mechanisms contributing toward their beneficial effects in these models.

PMID- 22470104
TI  - The acute effects of nicotine on the subjective and behavioural responses to
      denicotinized tobacco in dependent smokers.
AB  - Both nicotine and various non-nicotine smoking factors are believed to contribute
      to tobacco addiction but their relative roles remain incompletely understood.
      This study aimed to help clarify these roles by examining acute interactions
      between nicotine and denicotinized tobacco (DT). During two randomized blinded
      sessions, the effects of a quick-release 4 mg nicotine lozenge (NL) versus
      placebo lozenge (PL) on the subjective and behavioural responses to DT were
      examined in 27 (14 men) dependent, daily smokers. Participants were administered
      NL or PL for 30 min before receiving one initial DT cigarette. Participants could
      then earn additional DT cigarette puffs over the following 60 min. Subjective
      state was assessed using the Questionnaire of Smoking Urges-Brief and visual
      analogue scales at baseline, postlozenge and postinitial DT cigarette. Relative
      to PL, NL was associated with increased alertness as well as with reduced levels
      of DT self-administration (P<0.01). The administration of a single DT cigarette
      was followed by a reduction in craving under both lozenge conditions (P<0.001),
      an effect that was significantly greater in women (P<0.01). Moreover, DT
      administration was associated with increased ratings of 'pleasant', 'satisfied',
      'stimulated' and 'relaxed', as well as with decreased ratings of 'anxious'
      (P's<0.01), independent of lozenge condition. The findings suggest that both
      nicotine and non-nicotine smoking factors may make important contributions
      towards the addictive properties of tobacco.

PMID- 22470105
TI  - Lack of abuse potential in a highly selective dopamine D3 agonist, PF-592,379, in
      drug self-administration and drug discrimination in rats.
AB  - Dopamine D3-preferring agonists are commonly used to treat Parkinson's disease
      and restless leg syndrome; however, laboratory animal studies suggest that they
      may possess a moderate abuse potential. These studies aimed to compare the highly
      selective, full D3 agonist PF-592,379 to the less selective D3 agonist 7-OH-DPAT,
      and the indirect dopamine agonist cocaine in drug self-administration and
      discrimination assays. Although rats readily acquired high rates of fixed ratio
      (FR)1 responding for cocaine, experimentally naive rats failed to acquire
      responding when 7-OH-DPAT or PF-592,379 was made available during an 18-session
      acquisition period. Cocaine also maintained dose-dependent levels of responding
      when available under a FR5 or a progressive ratio (PR) schedule of reinforcement.
      Although 7-OH-DPAT maintained modest levels of responding when substituted under
      a FR5, it failed to maintain significant levels of PR responding. PF-592,379
      maintained saline-like rates of responding when substituted under FR5 or PR
      schedules of reinforcement. Similar behavioral profiles were observed in cocaine
      discrimination assays, with 7-OH-DPAT partially substituting for cocaine, and PF
      592,379 producing saline-like effects over a wide range of doses. Together, the
      results of these studies predict that highly selective D3 agonists, such as PF
      592,379, will have low abuse potential in humans.

PMID- 22470106
TI  - Pheophorbide a-mediated photodynamic therapy induces apoptotic cell death in
      murine oral squamous cell carcinoma in vitro and in vivo.
AB  - Photodynamic therapy (PDT) with several photosensitizers is a promising modality
      for the treatment of cancer. In this study, the therapeutic effect of PDT using
      the synthetic photosensitizer pheophorbide a (Pa-PDT) was examined in AT-84
      murine oral squamous cell carcinoma (OSCC) cells. The MTT assay revealed that Pa
      PDT induced cell growth inhibition in a dose- and time-dependent manner. Pa-PDT
      treatment significantly induced intracellular ROS generation, which is critical
      for cell death induced by Pa-PDT. Cell cycle analysis showed the increased sub-G1
      proportion of cells in Pa-PDT-treated cells. Induction of apoptotic cell death
      was confirmed by DAPI staining and the reduction of mitochondrial membrane
      potential (DeltaPsim) on Pa-PDT-treated cells. The changes in apoptosis-related
      molecules were next examined using western blotting. Cytochrome c release and
      cleavage of caspase-3 and PAPR were observed in AT-84 cells, whereas Bcl-2
      protein levels were decreased. To determine the therapeutic effect of Pa-PDT in
      vivo, a murine OSCC animal model was used. Treatment of mice with Pa-PDT
      significantly inhibited tumor growth, especially PDT with Pa intravenous
      administration (i.v. Pa-PDT), and increased proliferative cell nuclear antigen
      (PCNA) levels and TUNEL-stained apoptotic cells compared to vehicle-treated
      controls. The data demonstrate that the in vitro effects of Pa-PDT on the
      inhibition of tumor cell proliferation and induction of apoptosis correlate to
      the anticancer activity of Pa-PDT in vivo. Our findings suggest the therapeutic
      potential of Pa-PDT in OSCC.

PMID- 22470107
TI  - Acute effects of calcineurin inhibitors on kidney allograft microperfusion
      visualized by contrast-enhanced sonography.
AB  - BACKGROUND: Calcineurin inhibitors induce detrimental vascular remodeling, which
      may be one cause of chronic allograft failure. Real-time contrast-enhanced
      sonography (CES) is a relatively new technique in providing quantitative
      information on microvascular tissue perfusion in kidney allografts in more
      detail. The purpose of the study was to explore whether acute changes of kidney
      allograft microperfusion due to the administration of cyclosporine A (CsA) and
      tacrolimus (Tac) can be evidenced using real-time CES. METHODS: In an explorative
      single-center clinical trial, renal parenchymal tissue perfusion of 32 stable
      kidney allograft recipients was evaluated with CES before and 2 hr after the
      intake of CsA or Tac. In addition to laboratory and clinical parameters, Doppler
      indices and estimated glomerular filtration rate were measured. RESULTS: Although
      systolic and diastolic blood pressure and color Doppler indices did not
      significantly differ, there was a significant decrease of renal blood flow 2 hr
      after the intake of CsA compared with baseline (4.78+/-2.31 dB/s, 49%,
      respectively). In contrast, kidney allograft microperfusion was neither
      significantly reduced in patients receiving CsA paralleled by calcium channel
      blockers nor significantly reduced in patients receiving Tac. Furthermore, there
      was a significant correlation between renal blood flow obtained before drug
      administration and kidney function. CONCLUSIONS: CES revealed a 49% reduction of
      kidney allograft microperfusion 2 hr after the intake of CsA, which might be
      abrogated by calcium channel blockers. In comparison to CsA, Tac did not result
      in a significant decrease of kidney blood flow.

PMID- 22470108
TI  - Involvement of reactive oxygen species and JNK in increased expression of MCP-1
      and infiltration of inflammatory cells in pressure-overloaded rat hearts.
AB  - Increasing evidence has shown that inflammation is involved in pressure overload
      induced cardiac remodeling. Monocyte chemoattractant protein-1 (MCP-1) plays a
      pivotal role in the inflammatory process. However, the mechanisms underlying the
      upregulation of MCP-1 expression remain poorly understood. In the present study,
      we examined the hypothesis that an increased production of reactive oxygen
      species (ROS) mediates the upregulation of MCP-1. In a pressure-overloaded rat
      heart model with abdominal aortic coarctation (AC), superoxide dismutase
      inhibitable cytochrome C reduction assay showed that ROS generation in the
      myocardium increased significantly at 1 week by 61% (n=8, P<0.01), peaked at 2
      weeks and maintained these high levels for 4 weeks. The elevation of ROS was
      paralleled by the increased expression of MCP-1 and left ventricular remodeling
      (cardiac hypertrophy, perivascular and interstitial fibrosis). The oral
      administration of the antioxidant, N-acetylcysteine (NAC, 0.2 g/kg/day), for 2 or
      4 weeks, significantly attenuated ROS production by 69 and 68%, respectively
      (n=8, P<0.01), as well as left ventricular remodeling. NAC treatment for 2 weeks
      also significantly reduced the MCP-1 mRNA and protein levels by 52 and 60%,
      respectively (n=4-8, both P<0.01), but had no effect on blood pressure. In the
      rats with AC at 2 weeks, when MCP-1 expression and inflammation changes were
      overt, immunoblotting with phospho-specific antibodies revealed that
      extracellular regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), but not
      p38 mitogen-activated protein kinase, were activated. NAC administration
      attenuated JNK activation, but had no effect on ERK. Our results suggest that
      increased ROS production may play an important role in the increased expression
      of MCP-1 in pressure overload-induced cardiac remodeling. JNK is likely involved
      in the signaling pathway.

PMID- 22470109
TI  - 17-Allylamino-17-demethoxygeldanamycin and ritonavir inhibit renal cancer growth
      by inhibiting the expression of heat shock factor-1.
AB  - Our previous study showed that the combination of a histone deacetylase (HDAC)
      inhibitor and an HIV protease inhibitor is effective against renal cancer cells.
      Because HDAC inhibition disrupts the chaperon function of heat shock protein
      (HSP) 90, we hypothesized that the combination of 17-allylamino-17
      demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, and the HIV protease
      inhibitor ritonavir would also act against renal cancer. The combination of 17
      AAG and ritonavir induced apoptosis and inhibited the proliferation of renal
      cancer cells effectively. It also suppressed the expression of cyclin-dependent
      kinase 4 and cyclin D1, leading to the accumulation of the cells in the sub-G1
      fraction. The expression of HSPs 27, 70 and 90 was increased by 17-AAG alone but
      reduced by 17-AAG combined with ritonavir. The combination decreased the
      expression of heat shock factor-1 (HSF-1), an HSP transcription factor, and this
      might be one of the mechanisms of the effect of the combination. We have also
      found that silencing of HSF-1 by siRNA inhibited the proliferation of renal
      cancer cells and that in surgically resected specimens the levels of HSF-1
      expression in renal cancer tissue are higher than those in normal parenchyma.
      This is the first study showing the beneficial effect of combining 17-AAG and
      ritonavir and our data suggest that HSF-1 may be a novel therapeutic target in
      the treatment of renal cancer.

PMID- 22470110
TI  - Pharmacokinetic/Pharmacodynamic predictors of clinical potency for hepatitis C
      virus nonnucleoside polymerase and protease inhibitors.
AB  - This analysis was conducted to determine whether the hepatitis C virus (HCV)
      viral kinetics (VK) model can predict viral load (VL) decreases for nonnucleoside
      polymerase inhibitors (NNPolIs) and protease inhibitors (PIs) after 3-day
      monotherapy studies of patients infected with genotype 1 chronic HCV. This
      analysis includes data for 8 NNPolIs and 14 PIs, including VL decreases from 3
      day monotherapy, total plasma trough concentrations on day 3 (C(min)), replicon
      data (50% effective concentration [EC(50)] and protein-shifted EC(50)
      [EC(50,PS)]), and for PIs, liver-to-plasma ratios (LPRs) measured in vivo in
      preclinical species. VK model simulations suggested that achieving additional
      log(10) VL decreases greater than one required 10-fold increases in the C(min).
      NNPolI and PI data further supported this result. The VK model was successfully
      used to predict VL decreases in 3-day monotherapy for NNPolIs based on the
      EC(50,PS) and the day 3 C(min). For PIs, however, predicting VL decreases using
      the same model and the EC(50,PS) and day 3 C(min) was not successful; a model
      including LPR values and the EC(50) instead of the EC(50,PS) provided a better
      prediction of VL decrease. These results are useful for designing phase 1
      monotherapy studies for NNPolIs and PIs by clarifying factors driving VL
      decreases, such as the day 3 C(min) and the EC(50,PS) for NNPolIs or the EC(50)
      and LPR for PIs. This work provides a framework for understanding the
      pharmacokinetic/pharmacodynamic relationship for other HCV drug classes. The
      availability of mechanistic data on processes driving the target concentration,
      such as liver uptake transporters, should help to improve the predictive power of
      the approach.

PMID- 22470111
TI  - Evaluation of standard- and high-dose daptomycin versus linezolid against
      vancomycin-resistant Enterococcus isolates in an in vitro
      pharmacokinetic/pharmacodynamic model with simulated endocardial vegetations.
AB  - Daptomycin MICs for enterococci are typically 1- to 2-fold higher than those for
      Staphylococcus aureus, and there is an imminent need to establish the optimal
      dose for appropriate treatment of enterococcal infections. We investigated the
      bactericidal activity of daptomycin at various dose exposures compared to that of
      linezolid against vancomycin-resistant enterococcus (VRE) in an in vitro
      pharmacokinetic/pharmacodynamic model utilizing simulated endocardial vegetations
      over 96 h. Daptomycin at doses of 6, 8, 10, and 12 mg/kg of body weight/day and
      linezolid at a dose of 600 mg every 12 h were evaluated against two clinical
      vancomycin-resistant Enterococcus faecium strains (EFm11499 and 09-184D1051), one
      of which was linezolid resistant (09-184D1051), and one clinical vancomycin
      resistant Enterococcus faecalis strain (EFs11496). Daptomycin MICs were 4, 2, and
      0.5 MUg/ml for EFm11499, 09-184D1051, and EFs11496, respectively. Bactericidal
      activity, defined as a >= 3 log(10) CFU/g reduction from the initial colony
      count, was demonstrated against all three isolates with all doses of daptomycin;
      however, bactericidal activity was not sustained with the daptomycin 6- and 8
      mg/kg/day regimens. Linezolid was bacteriostatic against EFm11499 and displayed
      no appreciable activity against 09-184D1051 or EFs11496. Concentration-dependent
      killing was displayed with more sustained reduction in colony count (3.58 to 6.46
      and 5.89 to 6.56 log(10) CFU/g) at 96 h for the simulated regimen of daptomycin
      at doses of 10 and 12 mg/kg/day, respectively (P <= 0.012). No E. faecium mutants
      with reduced susceptibility were recovered at any dosage regimen; however, the E.
      faecalis strain developed reduced daptomycin susceptibility with daptomycin at 6,
      8, and 10 but not at 12 mg/kg/day. Daptomycin displayed a dose-dependent response
      against three VRE isolates, with high-dose daptomycin producing sustained
      bactericidal activity. Further research is warranted.

PMID- 22470114
TI  - Stability of extemporaneously prepared 0.5-percent caspofungin eye drops: a
      potential cost-savings exercise.
AB  - While the successful use of topical caspofungin for patients has been reported,
      topical caspofungin is not commercially available and its stability is unknown,
      limiting its usefulness in treating fungal keratitis. Caspofungin (0.5%) eye
      drops were aseptically prepared, and the concentrations were measured using a
      validated high-performance liquid chromatography (HPLC) analysis. The
      preparations remained stable for 28 days under refrigerated condition but not at
      25.0  degrees C. Our study supports the cost-saving use of caspofungin eye drops
      in the clinical setting.

PMID- 22470112
TI  - Sterilizing activities of novel combinations lacking first- and second-line drugs
      in a murine model of tuberculosis.
AB  - Novel oral regimens composed of new drugs with potent activity against
      Mycobacterium tuberculosis and no cross-resistance with existing agents are
      needed to shorten and simplify treatment for both drug-susceptible and drug
      resistant tuberculosis. As part of a continuing effort to evaluate novel drug
      combinations for treatment-shortening potential in a murine model, we performed
      two long-term, relapse-based experiments. In the first experiment, several 3- and
      4-drug combinations containing new agents currently in phase 2/3 trials (TMC207
      [bedaquiline], PA-824 and PNU-100480 [sutezolid], and/or clofazimine) proved
      superior to the first-line regimen of rifampin, pyrazinamide, and isoniazid.
      TMC207 plus PNU-100480 was the most effective drug pair. In the second
      experiment, in which 3- and 4-drug combinations composed of TMC207 and
      pyrazinamide plus rifapentine, clofazimine, PNU-100480, or both rifapentine and
      clofazimine were evaluated, the rank order of drugs improving the sterilizing
      activity of TMC207 and pyrazinamide was as follows: rifapentine plus clofazimine
      >= clofazimine >= rifapentine > PNU-100480. The results revealed potential new
      building blocks for universally active short-course regimens for drug-resistant
      tuberculosis. The inclusion of pyrazinamide against susceptible isolates may
      shorten the duration of treatment further.

PMID- 22470113
TI  - Antischistosomal activities of mefloquine-related arylmethanols.
AB  - Interesting antischistosomal properties have been documented for the antimalarial
      mefloquine, a 4-quinolinemethanol. We evaluated the antischistosomal activities
      of nine mefloquine-related compounds belonging to the 4-pyridinemethanols, 9
      phenanthrenmethanols, and 4-quinolinemethanols. Eight compounds revealed high
      activities against Schistosoma mansoni in vitro, with two drugs (the 4
      quinolinemethanols WR7573 and WR7930) characterized by significantly lower half
      maximal inhibitory concentrations (IC(50)s) (2.7 and 3.5 MUM, respectively)
      compared to mefloquine (11.4 MUM). Mefloquine and WR7930 showed significantly
      decreased IC(50)s when incubated in the presence of hemoglobin. High worm burden
      reductions (WBR) were obtained with enpiroline (WBR, 82.7%; dosage, 200 mg/kg of
      body weight) and its threo isomers (+)-threo (WBR, 100%) and (-)-threo (WBR, 89%)
      and with WR7930 (WBR, 87%; dosage, 100 mg/kg) against adult S. mansoni in mice.
      Furthermore, excellent in vitro and in vivo antischistosomal activity was
      observed for two WR7930-related structures (WR29252 and WR7524). In addition,
      mefloquine (WBR, 81%), enpiroline (WBR, 77%), and WR7930 (WBR, 100%) showed high
      activities against S. haematobium harbored in mice following single oral doses of
      200 mg/kg. These results provide a deeper insight into the structural features of
      the arylmethanols that rule antischistosomal activity. Further studies should be
      launched with enpiroline and WR7930.

PMID- 22470115
TI  - Summary of ceftaroline activity against pathogens in the United States, 2010:
      report from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE)
      surveillance program.
AB  - The Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance
      program is a sentinel resistance monitoring system designed to track the activity
      of ceftaroline and comparator agents. In the United States, a total of 8,434
      isolates were collected during the 2010 surveillance program from 65 medical
      centers distributed across the nine census regions (5 to 10 medical centers per
      region). All organisms were isolated from documented infections, including 3,055
      (36.2%) bloodstream infections, 2,282 (27.1%) respiratory tract infections, 1,965
      (23.3%) acute bacterial skin and skin structure infections, 665 (7.9%) urinary
      tract infections, and 467 (5.5%) miscellaneous other infection sites. Ceftaroline
      was the most potent beta-lactam agent tested against staphylococci. The MIC(90)
      values were 1 MUg/ml for methicillin-resistant Staphylococcus aureus (MRSA; 98.4%
      susceptible) and 0.5 MUg/ml for methicillin-resistant coagulase-negative
      staphylococci (CoNS). Ceftaroline was 16- to 32-fold more potent than ceftriaxone
      against methicillin-susceptible staphylococcal strains. All staphylococcus
      isolates (S. aureus and CoNS) were inhibited at ceftaroline MIC values of <= 2
      MUg/ml. Ceftaroline also displayed potent activity against streptococci (MIC(90),
      0.015 MUg/ml for beta-hemolytic streptococci; MIC(90), 0.25 MUg/ml for penicillin
      resistant Streptococcus pneumoniae). Potent activity was also shown against Gram
      negative pathogens (Haemophilus influenzae, Haemophilus parainfluenzae, and
      Moraxella catarrhalis). Furthermore, wild-type strains of Enterobacteriaceae (non
      extended-spectrum beta-lactamase [ESBL]-producing strains and non-AmpC
      hyperproducing strains) were often susceptible to ceftaroline. Continued
      monitoring through surveillance networks will allow for the assessment of the
      evolution of resistance as this new cephalosporin is used more broadly to provide
      clinicians with up-to-date information to assist in antibiotic stewardship and
      therapeutic decision making.

PMID- 22470116
TI  - Impact of two-component regulatory systems PhoP-PhoQ and PmrA-PmrB on colistin
      pharmacodynamics in Pseudomonas aeruginosa.
AB  - The in vitro pharmacodynamics of colistin against Pseudomonas aeruginosa PAO1
      wild-type and isogenic knockout strains of phoP and pmrA were evaluated. Colistin
      killing at subinhibitory concentrations was greater against the phoP and pmrA
      mutants than the wild type within the first 8 h: the concentration that results
      in 50% of maximal effect (EC(50)) of the pmrA mutant (0.413 mg/liter) was less
      than that of the wild type (0.718 mg/liter) (P < 0.05). An in vitro
      pharmacodynamic model simulating human colistin regimens displayed initial
      killing followed by regrowth in the phoP mutant and gradual regrowth in the pmrA
      mutant and wild type.

PMID- 22470117
TI  - Influence of antituberculosis drug resistance and Mycobacterium tuberculosis
      lineage on outcome in HIV-associated tuberculous meningitis.
AB  - HIV-associated tuberculous meningitis (TBM) has high mortality. Aside from the
      devastating impact of multidrug resistance (MDR) on survival, little is
      understood about the influence of other bacterial factors on outcome. This study
      examined the influence of Mycobacterium tuberculosis drug resistance, bacterial
      lineage, and host vaccination status on outcome in patients with HIV-associated
      TBM. Mycobacterium tuberculosis isolates from the cerebrospinal fluid of 186
      patients enrolled in two studies of HIV-associated TBM in Ho Chi Minh City,
      Vietnam, were tested for resistance to first-line antituberculosis drugs. Lineage
      genotyping was available for 122 patients. The influence of antituberculosis drug
      resistance and M. tuberculosis lineage on 9-month mortality was analyzed using
      Kaplan-Meier survival analysis and Cox multiple regression models. Isoniazid
      (INH) resistance without rifampin resistance was associated with increased
      mortality (adjusted hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.18
      to 2.66; P = 0.005), and multidrug resistance was uniformly fatal (n = 8/8;
      adjusted HR, 5.21, 95% CI, 2.38 to 11.42; P < 0.0001). The hazard ratio for INH
      resistant cases was greatest during the continuation phase of treatment (after 3
      months; HR, 5.05 [95% CI, 2.23 to 11.44]; P = 0.0001). Among drug-susceptible
      cases, patients infected with the "modern" Beijing lineage strains had lower
      mortality than patients infected with the "ancient" Indo-Oceanic lineage (HR,
      0.29 [95% CI, 0.14 to 0.61]; P = 0.001). Isoniazid resistance, multidrug
      resistance, and M. tuberculosis lineage are important determinants of mortality
      in patients with HIV-associated TBM. Interventions which target these factors may
      help reduce the unacceptably high mortality in patients with TBM.

PMID- 22470118
TI  - Effect of coadministration of moxifloxacin and rifampin on Mycobacterium
      tuberculosis in a murine aerosol infection model.
AB  - Coadministration of moxifloxacin and rifampin was evaluated in a murine model of
      Mycobacterium tuberculosis pulmonary infection to determine whether the finding
      of antagonism documented in a hollow-fiber infection model could be recapitulated
      in vivo. Colony counts were followed in a no-treatment control group, groups
      administered moxifloxacin or rifampin monotherapy, and a group administered a
      combination of the two agents. Following 18 days of once-daily oral
      administration to mice infected with M. tuberculosis, there was a reduction in
      the plasma exposure to rifampin that decreased further when rifampin was
      coadministered with moxifloxacin. Pharmacodynamic analysis demonstrated a mild
      antagonistic interaction between moxifloxacin and rifampin with respect to cell
      kill in the mouse model for tuberculosis (TB). No emergence of resistance was
      noted over 28 days of therapy, even with monotherapy. This was true even though
      one of the agents in the combination (moxifloxacin) induces error-prone
      replication. The previously noted antagonism with respect to cell kill shown in
      the hollow-fiber infection model was recapitulated in the murine TB lung model,
      although to a lesser extent.

PMID- 22470119
TI  - Pharmacokinetic comparison of two piperaquine-containing artemisinin combination
      therapies in Papua New Guinean children with uncomplicated malaria.
AB  - Pharmacokinetic differences between piperaquine (PQ) base and PQ tetraphosphate
      were investigated in 34 Papua New Guinean children aged 5 to 10 years treated for
      uncomplicated malaria with artemisinin-PQ (ART-PQ) base or dihydroartemisinin-PQ
      (DHA-PQ) tetraphosphate. Twelve children received ART-PQ base (two daily doses of
      3 mg of ART and 18 mg of PQ base as granules/kg of body weight) as recommended by
      the manufacturer, with regular clinical assessment and blood sampling over 56
      days. PQ concentrations in plasma samples collected from 22 children of similar
      ages with malaria in a previously published pharmacokinetic study of DHA-PQ
      tetraphosphate (three daily doses of 2.5 mg of ART and 20 mg of PQ tetraphosphate
      as tablets/kg of body weight) were available for comparison. The disposition of
      ART was also assessed in the 12 children who received ART-PQ base. Plasma PQ was
      assayed by high-performance liquid chromatography with UV detection, and ART was
      assayed using liquid chromatography-mass spectrometry. Multicompartment
      pharmacokinetic models for PQ and ART were developed using a population-based
      approach. ART-PQ base was well tolerated, and initial fever abatement and
      parasite clearance were prompt. There were no differences between the two
      treatments in the values for the PQ area under the concentration-time curve from
      time zero to infinity (AUC(0-infinity)), with medians of 49,451 (n = 12) and
      44,556 (n = 22) MUg . h/liter for ART-PQ base and DHA-PQ tetraphosphate,
      respectively. Recurrent parasitemia was associated with lower PQ exposure. Using
      a two-compartment ART model, the median AUC(0-infinity) was 1,652 MUg . h/liter.
      There was evidence of autoinduction of ART metabolism (relative bioavailability
      for the second dose, 0.27). These and previously published data suggest that a 3
      day ART-PQ base regimen should be further evaluated, in line with World Health
      Organization recommendations for all artemisinin combination therapies.

PMID- 22470120
TI  - Evaluation of a mouse model of necrotic granuloma formation using C3HeB/FeJ mice
      for testing of drugs against Mycobacterium tuberculosis.
AB  - Persistence of Mycobacterium tuberculosis remains a significant challenge for the
      effective treatment of tuberculosis in humans. In animals that develop necrotic
      lung lesions following infection with M. tuberculosis, drug-tolerant bacilli are
      present and persist in an extracellular microenvironment within the necrotic
      cores. In this study, we examined the efficacy of drug treatment in C3HeB/FeJ
      (Kramnik) mice that develop lesions with liquefactive necrosis, in comparison to
      BALB/c mice that develop nonnecrotic lesions following aerosol challenge. To
      accomplish this, Kramnik and BALB/c mice were infected by aerosol with M.
      tuberculosis and treated for 7 to 8 weeks with monotherapy using drugs with
      different modes of action. The efficacy of drug therapy was quantified by
      enumeration of bacterial load. The progression of disease and location and
      distribution of bacilli within lesions were visualized using various staining
      techniques. In the late stages of infection, Kramnik mice developed fibrous
      encapsulated lung lesions with central liquefactive necrosis containing abundant
      extracellular bacilli, whereas BALB/c mice formed nonnecrotic lesions with
      primarily intracellular bacilli. Necrotic lesions in Kramnik mice showed evidence
      of hypoxia by pimonidazole staining. Kramnik mice were significantly more
      refractory to drug therapy, especially for pyrazinamide. Metronidazole showed no
      bactericidal activity in either model. There were significantly higher numbers of
      drug-resistant colonies isolated from the Kramnik mice compared to BALB/c mice.
      These results suggest that the Kramnik mouse model will be a valuable model to
      test antituberculosis drugs, especially against bacilli that persist within
      necrotic lesions.

PMID- 22470122
TI  - Use of Carbapenems against clinical, nontyphoid Salmonella isolates: results from
      in vitro and in vivo animal studies.
AB  - The emergence of multidrug-resistant Salmonella isolates has created the need for
      new therapeutic agents. We evaluated the intracellular activity of four
      carbapenem compounds against clinical nontyphoid Salmonella (NTS) isolates in
      vitro and ex vivo. Subsequently, the efficacy of carbapenem treatment against
      selected Salmonella isolates in vivo was assessed using a murine peritonitis
      model. The MIC(50) and MIC(90) for doripenem, ertapenem, imipenem, and meropenem
      against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5
      and 1, and 0.031 and 0.031 MUg/ml, respectively. The intracellular killing effect
      of ertapenem was sustained for 24 h and was superior to that of imipenem,
      meropenem, and doripenem; its effect was comparable to that of ceftriaxone.
      Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time
      above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio
      of 20,733. When peritoneal exudate cells were examined directly ex vivo from mice
      with Salmonella-induced peritonitis, cells from mice treated with ertapenem and
      ceftriaxone had intracellular and extracellular bacterial counts reduced 10(2)-
      to 10(4)-fold and exhibited killing effects similar to each other. The survival
      rates of mice inoculated with 1 * 10(5) and 10(6) CFU of a ceftriaxone
      susceptible Salmonella isolate that were subsequently treated with ertapenem or
      ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 *
      10(4) and 10(5) CFU of a ceftriaxone-resistant and ciprofloxacin-resistant
      Salmonella isolate, mice treated with ertapenem had a higher survival rate than
      mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively; P <
      0.001). Our results suggest that ertapenem is at least as effective as
      ceftriaxone in treating murine Salmonella infections and show that further
      clinical investigations on the potential use of ertapenem in treatment of human
      Salmonella infections are warranted.

PMID- 22470121
TI  - Effect of mutation and genetic background on drug resistance in Mycobacterium
      tuberculosis.
AB  - Bacterial factors may contribute to the global emergence and spread of drug
      resistant tuberculosis (TB). Only a few studies have reported on the interactions
      between different bacterial factors. We studied drug-resistant Mycobacterium
      tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in
      Switzerland. We determined quantitative drug resistance levels of first-line
      drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the
      hot-spot regions of the relevant genes. We determined recent transmission by
      molecular methods and collected clinical data. Overall, we analyzed 158 isolates
      that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which
      were multidrug resistant. Among 154 isoniazid-resistant strains, katG mutations
      were associated with high-level and inhA promoter mutations with low-level drug
      resistance. Only katG(S315T) (65.6% of all isoniazid-resistant strains) and inhA
      promoter -15C/T (22.7%) were found in molecular clusters. M. tuberculosis lineage
      2 (includes Beijing genotype) was associated with any drug resistance (adjusted
      odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6; P < 0.0001).
      Lineage 1 was associated with inhA promoter -15C/T mutations (OR, 6.4; 95% CI,
      2.0 to 20.7; P = 0.002). We found that the genetic strain background influences
      the level of isoniazid resistance conveyed by particular mutations (interaction
      tests of drug resistance mutations across all lineages; P < 0.0001). In
      conclusion, M. tuberculosis drug resistance mutations were associated with
      various levels of drug resistance and transmission, and M. tuberculosis lineages
      were associated with particular drug resistance-conferring mutations and
      phenotypic drug resistance. Our study also supports a role for epistatic
      interactions between different drug resistance mutations and strain genetic
      backgrounds in M. tuberculosis drug resistance.

PMID- 22470124
TI  - Apple polysaccharides induce apoptosis in colorectal cancer cells.
AB  - Certain components of apples have been shown to prevent cancer growth and impede
      cancer progression. We hypothesized that extracted apple polysaccharides (APs)
      might, therefore, have anticancer effects, through a mechanism involving the
      induction of apoptosis in cancer cells, partly via the NF-kappaB pathway. Two
      human colorectal cancer (CRC) cell lines, HT-29 and SW620, were exposed to
      different concentrations of APs (0.01, 0.1 or 1 mg/ml). Cell apoptosis was
      measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay by flow cytometry and incorporation of 5'-bromodeoxyuridine (BrdU) into DNA
      to identify the proliferating cell fraction, using fluorescence microscopy in
      vitro. The protein levels of NF-kappaB/p65, I-kappaBalpha, pI-kappaBalpha, Bax,
      Bcl-xl and Bcl-2 were evaluated by western blotting. The target sites of APs on
      CRC cells were assessed by flow cytometry. At concentrations of 0.1 and 1 mg/ml,
      APs showed apoptosis-inducing effects, increased expressions of Bax, nuclear p65
      and cytoplasmic pI-kappaBalpha, and decreased expressions of Bcl-2, Bcl-xl and
      cytoplasmic I-kappaBalpha. APs induced apoptosis by slightly activating the NF
      kappaB pathway; the AP target site could be the Toll-like receptor 4 on the cell
      membrane. These results demonstrate the potential of APs as agents for clinical
      prevention and treatment of CRC.

PMID- 22470123
TI  - Ovarian abnormalities in a mouse model of fragile X primary ovarian
      insufficiency.
AB  - FMR1 premutation (PM) alleles have 55-200 CGG.CCG-repeats in their 5' UTR. PM
      carriers are at risk of fragile X-associated tremor and ataxia syndrome (FXTAS).
      Females are also at risk for FX primary ovarian insufficiency (FXPOI). PM
      pathology is generally attributed to deleterious properties of transcripts with
      long CGG-tracts. For FXPOI, hormone changes suggest a reduced residual follicle
      pool. Whether this is due to a smaller than normal original follicle pool or an
      increased rate of follicle depletion is unclear. A FX-PM mouse the authors
      generated with 130 CGG.CCG-repeats in the endogenous Fmr1 gene recapitulates
      features of FXTAS. Here the authors demonstrate that the gross development of the
      ovary and the establishment of the primordial follicle pool is normal in these
      mice. However, these animals show a faster loss of follicles of all follicle
      classes, suggesting that the problem is intrinsic to the ovary. In addition, many
      oocytes show aberrant nuclear accumulation of FMRP and elevated levels of
      ubiquitination. Furthermore, PM follicles are smaller and have fewer granulosa
      cells (GCs) than normal. Thus, these animals have ovarian abnormalities involving
      both the oocytes and GCs that may shed light on the molecular basis of FXPOI in
      humans.

PMID- 22470125
TI  - Prognostic significance of metadherin overexpression in hepatitis B virus-related
      hepatocellular carcinoma.
AB  - Metadherin (MTDH), which is an HIV-1 or TNF-alpha-inducible transcript, has a
      crucial role in several types of cancer by regulating multiple cellular signaling
      processes. However, to date, the role of MTDH in hepatitis B virus (HBV)-related
      hepatocellular carcinoma (HCC) is still unclear. In the present study, we
      detected MTDH expression in normal liver, chronic hepatitis B and HBV-related HCC
      tissues. The data showed that MTDH expression levels were elevated in the
      hepatitis B tissues and especially in the HBV-related HCC tissues compared to
      normal liver tissues. There was a trend for gradually increased MTDH expression
      from normal liver tissue to hepatitis B and HBV-related HCC tissues. Furthermore,
      a statistical analysis revealed that MTDH expression significantly correlated
      with the American Joint Committee on Cancer (AJCC, 7th edition) stage (P=0.020),
      T classification (P=0.007), N classification (P=0.044), vascular invasion
      (P=0.006) and histological differentiation (P=0.020) in the HBV-related HCC
      patients. In addition, patients with high MTDH levels had shorter survival times
      compared to those with low MTDH expression (P=0.001). Taken together, these
      results suggest that MTDH could be a potential prognostic marker for overall
      survival and tumor progression and a chemotherapeutic target in HBV-related HCC
      patients.

PMID- 22470126
TI  - One-dimensional SDS gel electrophoresis of proteins.
AB  - One-dimensional gel electrophoresis of proteins provides information about the
      molecular size, amount, and purity of a protein sample. Separated proteins can be
      recovered from polyacrylamide gels for subsequent characterization by a variety
      of secondary techniques, such as mass spectrometry to determine post
      translational modifications and the amino acid sequence. In addition, one
      dimensional electrophoresis is the standard first step in immunoblotting and
      immunodetection. Protein separations in vertical slab gels are performed in a
      variety of formats. Most recently, small format minigels are typical due to their
      ease of use, low relative cost, and ready commercial availability. Larger gels
      provide more separation area and thus better resolution for complex samples and
      continue to be in use for specialized analysis.

PMID- 22470127
TI  - Use of CID/ETD mass spectrometry to analyze glycopeptides.
AB  - Collision-induced dissociation (CID) tandem mass spectrometry (MS/MS) does not
      allow the characterization of glycopeptides because of the fragmentation of
      glycan structures and limited fragmentation of peptide backbones. Electron
      transfer dissociation (ETD) MS/MS, on the other hand, offers a complementary
      approach, prompting only peptide backbone fragmentation while keeping post
      translational modifications intact. Characterization of glycopeptides using both
      CID and ETD is summarized in this unit. While CID provides information related to
      the composition of glycan moieties attached to a peptide backbone, ETD permits de
      novo sequencing of peptides. Radical anion transfer of electrons to the peptide
      backbone in ETD induces cleavage of the N-Calpha bond. The glycan moiety is
      retained on the peptide backbone, largely unaffected by the ETD process, thus
      allowing the identification of the amino acid sequence of a glycopeptide and its
      glycosylation site. This unit discusses the use of both CID and ETD for better
      characterization of glycopeptides.

PMID- 22470128
TI  - Overview of protein folding mechanisms: experimental and theoretical approaches
      to probing energy landscapes.
AB  - We present an overview of the current experimental and theoretical approaches to
      studying protein folding mechanisms, set against current models of the folding
      energy landscape. We describe how stability and folding kinetics can be
      determined experimentally and how this data can be interpreted in terms of the
      characteristic features of various models from the simplest two-state pathway to
      a multi-state mechanism. We summarize the pros and cons of a range of
      spectroscopic methods for measuring folding rates and present a theoretical
      framework, coupled with protein engineering approaches, for elucidating folding
      mechanisms and structural features of folding transition states. A series of case
      studies are used to show how experimental kinetic data can be interpreted in the
      context of non-native interactions, populated intermediates, parallel folding
      pathways, and sequential transition states. We also show how computational
      methods now allow transient species of high energy, such as folding transition
      states, to be modeled on the basis of experimental Phi-value analysis derived
      from the effects of point mutations on folding kinetics.

PMID- 22470129
TI  - HPLC-SEC characterization of membrane protein-detergent complexes.
AB  - Determination of the oligomeric state of integral membrane proteins in detergent
      solutions is a challenging task because the amount of detergent associated with
      the protein is typically unknown and unpredictable. Methods that estimate the
      molecular weight of proteins from their hydrodynamic properties in solution are
      not suitable for detergent-solubilized membrane proteins. However, size-exclusion
      chromatography (SEC) performed in combination with analyses of static light
      scattering (SLS), ultraviolet absorbance (UV), and refractive index (RI) provides
      a universal method for determination of the molar masses of biopolymers and
      protein-detergent complexes. The light scattered by a protein is directly
      proportional to its molecular mass, irrespective of shape, and any additional
      contributions due to bound detergent molecules can be quantitatively accounted
      for by the additional combined analysis of ultraviolet absorbance and refractive
      index information. The primary intention of this unit is to describe how to apply
      the combination of high-performance liquid chromatography SEC and SLS-UV-RI to
      evaluate molecular mass and the physicochemical heterogeneity of purified
      membrane protein-detergent complexes.

PMID- 22470130
TI  - miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour
      growth by inhibiting GABA receptors.
AB  - An altered expression of microRNAs (miRNAs) contributes both to the development
      of cancer and to the progression of the disease. Malignant tumours and tumour
      cell lines have widespread deregulated expressions of miRNAs compared to normal
      tissues. In this study, we investigated the expression profiles of 340 mammalian
      miRNAs in 93 cases of multiform glioblastoma (primary and secondary glioblastoma
      tumours), by means of DNA microarrays. We show that the expression profiles of 10
      miRNAs can distinguish primary from secondary glioblastoma types. Moreover, we
      found elevated miR-155 levels in primary and secondary glioblastoma tissues as
      well as in glioblastoma primary cultures. We hypothesised that gamma-aminobutyric
      acid A receptor 1 (GABRA1) is a miR-155 target, and studied the correlation
      between miR-155 up-regulation and the GABRA1 protein in cultured glioblastoma
      cells by miRNA silencing. We show that a decrease in miR-155 expression to normal
      levels restores the expression of GABRA1, making glioblastoma cells sensitive to
      signals that inhibit cell proliferation mediated by GABRA1. In conclusion, the
      expression patterns of different miRNAs characterise primary and secondary
      glioblastomas. The aberrant overexpression of miR-155 contributes to the
      malignant phenotype of glioblastoma cells removing growth inhibition.

PMID- 22470131
TI  - Effect of hydrogen sulfide on restenosis of peripheral arteries after
      angioplasty.
AB  - Peripheral artery disease (PAD) may lead to a poor quality of life. Although
      percutaneous transluminal angioplasty (PTA) is widely used for the treatment of
      PAD, restenosis remains a major drawback. Hydrogen sulfide (H2S) plays potential
      roles in many physiological processes, such as vasodilatation and inhibition of
      smooth muscle cell proliferation. However, little is known regarding its role in
      arterial restenosis. In this study, we induced atherosclerotic-like lesions in
      rabbits, and we treated the rabbits with balloon angioplasty (BA) in a similar
      manner as PTA performed in the clinic. The rabbits were treated with sodium
      hydrosulfide (NaHS, a donor of H2S) or DL-propargylglycine (PPG, an inhibitor of
      H2S synthase). Treatment with NaHS significantly inhibited arterial restenosis
      following BA by reducing the intimal area and the intima/media ratio, while PPG
      treatment had a tendency to result in more severe restenosis. NaHS treatment
      significantly reduced smooth muscle cell (SMC) proliferation and elevated SMC
      apoptosis in the neointima. In contrast, PPG induced a significant increase in
      SMC proliferation. In conclusion, H2S attenuates the progression of neointimal
      hyperplasia and inhibits restenosis after BA. This discovery may lead to
      potential novel therapies, which can improve the prognosis of PAD patients.

PMID- 22470132
TI  - SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung metastasis of
      breast cancer in mice.
AB  - Silent information regulator 2 (SIR2) is a highly conserved protein, the
      mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity.
      SIRT1 is involved not in only longevity due to caloric restriction but in a
      variety of diseases such as diabetes, cardiovascular dysfunction and
      neurodegeneration. However, accumulating evidence shows that SIRT1 is
      overexpressed in various types of malignant cells, and its inhibitors suppress
      the growth of tumor cells. The relationship between SIRT1 and metastasis remains
      to be clarified. Here, we examined the effect of SRT1720, a SIRT1 activator, on
      lung metastasis of breast cancer cells. 4T1 breast cancer cells were
      subcutaneously implanted into syngeneic BALB/c mice and SRT1720 was administered
      alone or with an antitumor agent, cisplatin. As expected, cisplatin decreased the
      lung metastasis score, whereas SRT1720 increased metastasis irrespective of
      cisplatin. In the primary tumors, cisplatin suppressed the mRNA level of
      angiopoietin-like protein 4 (angptl4), a lung metastasis-promoting gene product
      of breast cancer, but SRT1720 reduced the effectiveness of cisplatin. The results
      obtained with animal experiments were in accordance with those in human cancer
      cells; SRT1720 significantly increased the amount of VEGF secreted from MDA-MB
      231 cells. Moreover, a transendothelial cell migration assay showed that SRT1720
      promotes the migration of MDA-MB-231 cells across an endothelial cell layer
      despite the presence of cisplatin. These findings imply that SRT1720 promotes the
      pulmonary metastasis of breast cancer cells and SIRT1 may be an important target
      for suppressing metastasis to the lung.

PMID- 22470133
TI  - Improving hospital outcomes in patients admitted from residential aged care:
      results from a controlled trial.
AB  - BACKGROUND: residents of aged care are old, frail and frequently require hospital
      management of intercurrent illness, but hospital outcomes are poor. OBJECTIVE: to
      identify the impact of an interdisciplinary care model on medical inpatients
      admitted from residential aged care (RAC). DESIGN: pre-planned subgroup analysis
      of controlled trial. SETTING: general medical units of a teaching hospital in
      Brisbane, Australia. SUBJECTS: consecutive patients aged over 65 admitted from
      RAC (n = 189) or the community (n = 815). METHODS: all admitted general medical
      patients were allocated by existing cyclical roster to control (usual care) or
      intervention units (interdisciplinary care consisting of improved allied health
      staffing, consistent teams, daily team meetings and early discharge planning).
      Patient characteristics and outcomes of care were compared between RAC and
      community subgroups. In the RAC subgroup, outcomes were compared between the
      control and intervention groups. RESULTS: patients admitted from RAC had much
      higher in-hospital mortality (13 versus 6%) and 6-month mortality (35 versus 17%)
      than those from community. RAC residents receiving the intervention had a
      significant reduction in in-hospital mortality (4 versus 22% P < 0.001) sustained
      at 6 months (28 versus 44% P = 0.02). CONCLUSIONS: poor hospital outcomes for RAC
      residents may reflect prevailing models of inpatient care.

PMID- 22470134
TI  - Target-induced natural killer cell loss as a measure of NK cell responses.
AB  - Natural killer (NK) cells are an important effector cell of innate immunity.
      Their interaction with susceptible target cells triggers NK cell cytotoxicity and
      the release of cytokines. Immunofluorescence flow cytometry-based assays are now
      the preferred methods for measuring NK cell responses. For these assays,
      assessment is made on NK cells (CD3(-)CD56(+) CD16(+)) within the viable
      lymphocyte gate, defined by the parameters of size (FSC) and granularity (SSC).
      Accordingly, NK cells that have not dissociated from target cells at the time of
      measurement, or that have undergone target cell-induced apoptosis, are excluded
      from the viable lymphocyte gate and therefore from analysis. This unit describes
      a protocol for assessing NK cell function in response to target cells (both
      natural killing and antibody-dependent cell cytotoxicity) based on the loss of NK
      cells from the lymphocyte gate. This target-induced NK loss (TINKL) should
      provide a sensitive measure of NK cell responses in a clinical laboratory
      setting.

PMID- 22470135
TI  - Analysis of the targeting properties of Fc chimeric proteins and antibodies in
      mice in vivo.
AB  - This unit includes protocols for the analysis of the targeting properties of Fc
      chimeric proteins and antibodies in mice in vivo. We present procedures to
      prepare the reagents to be tested under endotoxin-free conditions, suitable
      injection sites, methodology for tissue collection, and processing, and labeling
      procedures to detect the injected material in situ.

PMID- 22470136
TI  - Differentiation of mast cells from embryonic stem cells.
AB  - In this unit, we describe a simple coculture-free method for obtaining mast cells
      from mouse and human embryonic stem (ES) cells. Much of our knowledge regarding
      the mechanisms by which mast cells are activated comes from studies of mouse bone
      marrow-derived mast cells. Studies of human mast cells have been hampered by the
      limited sources from which they can be cultured, the difficulty in introducing
      specific genetic changes into these cells, and differences between established
      cultures that reflect the unique genetic makeup of the tissue donor. Derivation
      of mast cells from embryonic stem cells addresses these limitations. ES-derived
      mast cells can be generated in numbers sufficient for studies of the pathways
      involved in mast cell effector functions. These ES cell-derived mast cells
      respond to antigens and other stimuli by releasing histamine, cytokines, lipids,
      and other bioactive mediators. The derivation of human mast cells from ES cells
      carrying mutations introduced by homologous recombination should provide a novel
      means of testing the function of genes in both the development and the effector
      functions of mast cells.

PMID- 22470137
TI  - Isolation of cells from the feto-maternal interface.
AB  - The mucosal lining of the human uterus is host to a specialized population of
      leukocytes, which, during pregnancy, interact with invading placental cells
      (trophoblast) of fetal origin. Of particular interest are uterine natural killer
      cells, which account for around 70% of the leukocytes at this site during the
      first trimester of pregnancy, and seem to be specially adapted to recognize
      invading trophoblast cells. In order to understand the interactions between
      mucosal immune cells and trophoblast, and those among the immune cells
      themselves, it is useful to be able to isolate and culture these cells. Here, we
      describe protocols for the isolation of leukocytes, stromal cells, and
      trophoblast cells from the feto-maternal interface.

PMID- 22470138
TI  - Puerarin inhibits caspase-3 expression in osteoblasts of diabetic rats.
AB  - The aim of this study was to investigate the protective effect of puerarin on
      attenuating caspase-3 expression in osteoblasts of streptozotocin-induced
      diabetic rats and the possible mechanisms involved. Diabetic rats were treated
      with a puerarin injection of 100 mg/kg/day. After 6 weeks, the bone mineral
      density, pathological changes and expression of caspase-3 were observed. The bone
      mineral density in the diabetic rats was significantly lower compared to the
      control group, while osteoblast numbers in the cortical bone were significantly
      reduced, and new bone formation in the diabetic rats was rare. Caspase-3
      expression in the osteoblasts of diabetic rats increased compared to the rats in
      the control group. These pathological changes were improved and caspase-3
      expression decreased in the puerarin-treated rats compared to the diabetic rats
      (P<0.01). High glucose levels affect bone metabolism and increase caspase-3
      expression in osteoblasts, and thus lead to diabetic osteoporosis. Puerarin may
      play a protective role in diabetic osteoporosis via the reduction of caspase-3
      expression.

PMID- 22470139
TI  - Lentivirus-mediated RNA interference targeting WWTR1 in human colorectal cancer
      cells inhibits cell proliferation in vitro and tumor growth in vivo.
AB  - WW domain-containing transcription regulator 1 (WWTR1) was initially identified
      as a transcriptional coactivator involved in the differentiation of stem cells as
      well as the development of multiple organs. Recently, WWTR1 has also been
      identified as a major component of the novel Hippo signalling pathway important
      for the development of breast and lung cancer. Here, we show for the first time
      that WWTR1 has an oncogenic function in colorectal cancer cell lines. Knockdown
      of WWTR1 by lentivirus-mediated RNA interference in human colorectal cancer cells
      significantly decreased cell proliferation and the colony formation of RKO cells
      in vitro and tumor growth in vivo. Furthermore, we found that the decreased
      proliferation was due to cell cycle arrest and increased apoptosis. In addition,
      efficient knockdown of WWTR1, demonstrated by quantitative real-time PCR, led to
      upregulation of ASNS and downregulation of SMAD3, LTBR, BAX and BAK1 in WWTR1
      knockdown cells, suggesting that these genes may be involved in the repression of
      cell proliferation. Our findings indicate that WWTR1 is an oncogene and has an
      important role in the proliferation of colorectal cancer cells and in tumor
      growth in vivo.

PMID- 22470140
TI  - Methods for detecting and correcting for population stratification.
AB  - Population stratification (PS) is a primary consideration in studies of the
      genetic determinants of human traits. Failure to control for it may lead to
      confounding, causing a study to fail for lack of significant results or resources
      to be wasted following false-positive signals. Here we review historical and
      current approaches for addressing PS when performing genetic association studies
      in human populations. We describe methods for detecting the presence of PS
      including global and local ancestry methods. We also describe approaches for
      accounting for PS when calculating association statistics, such that measures of
      association are not confounded. This is particularly important since many traits
      are being examined in minority populations, populations that may inherently
      feature PS.

PMID- 22470141
TI  - Metaphase harvest and cytogenetic analysis of malignant hematological specimens.
AB  - Cytogenetic analysis of malignant hematological disease is an important
      methodology used by clinicians and researchers, as observations of clonal
      chromosomal abnormalities have been shown to have both diagnostic and prognostic
      significance. The Basic Protocol describes culture, harvest, and preparation of
      chromosome spreads from bone marrow aspirates. Three alternate protocols describe
      adaptations of the Basic Protocol for preparation of specimens from chronic
      lymphocytic leukemia (CLL) blood/bone marrow, plasma cell disorders, mainly bone
      marrow multiple myeloma (MM), and "solid" hematological samples including lymph
      nodes and splenic tissue. The modifications involve slightly different culture
      and harvest methods that are necessary to assure optimal results.

PMID- 22470142
TI  - High-throughput multiplex sequencing of miRNA.
AB  - Next-generation sequencing offers many advantages over other methods of microRNA
      (miRNA) expression profiling, such as sample throughput and the capability to
      discover novel miRNAs. As the sequencing depth of current sequencing platforms
      exceeds what is necessary to quantify miRNAs, multiplexing several samples in one
      sequencing run offers a significant cost advantage. Although previous studies
      have achieved this goal by adding bar codes to miRNA libraries at the ligation
      step, this was recently shown to introduce significant bias into the miRNA
      expression data. This bias can be avoided, however, by bar coding the miRNA
      libraries at the PCR step instead. Here, we describe a user-friendly PCR bar
      coding method of preparing multiplexed microRNA libraries for Illumina-based
      sequencing. The method also prevents the production of adapter dimers and can be
      completed in one day.

PMID- 22470143
TI  - Biochemical genetics. Introduction.

PMID- 22470145
TI  - Searching Online Mendelian Inheritance in Man (OMIM) for information on genetic
      loci involved in human disease.
AB  - Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of
      information on human genes and genetic disorders, with a particular emphasis on
      the interplay between observed phenotypes and underlying genotypes. This unit
      focuses on the basic methodology for formulating OMIM searches and illustrates
      the types of information that can be retrieved from OMIM, including descriptions
      of clinical manifestations resulting from genetic abnormalities. This unit also
      provides information on additional relevant medical and molecular biology
      databases. A basic knowledge of OMIM should be part of the armamentarium of
      physicians and scientists with an interest in research on the clinical aspects of
      genetic disorders.

PMID- 22470144
TI  - Searching for non-B DNA-forming motifs using nBMST (non-B DNA motif search tool).
AB  - This unit describes basic protocols on using the non-B DNA Motif Search Tool
      (nBMST) to search for sequence motifs predicted to form alternative DNA
      conformations that differ from the canonical right-handed Watson-Crick double
      helix, collectively known as non-B DNA, and on using the associated PolyBrowse, a
      GBrowse-based genomic browser. The nBMST is a Web-based resource that allows
      users to submit one or more DNA sequences to search for inverted repeats
      (cruciform DNA), mirror repeats (triplex DNA), direct/tandem repeats
      (slipped/hairpin structures), G4 motifs (tetraplex, G-quadruplex DNA),
      alternating purine-pyrimidine tracts (left-handed Z-DNA), and A-phased repeats
      (static bending). The nBMST is versatile, simple to use, does not require
      bioinformatics skills, and can be applied to any type of DNA sequences, including
      viral and bacterial genomes, up to an aggregate of 20 megabasepairs (Mbp).

PMID- 22470146
TI  - NHS regulator may not be fit to register GP practices, MPs warn.

PMID- 22470147
TI  - Adeno-associated viral vectors for anterograde axonal tracing with fluorescent
      proteins in nontransgenic and cre driver mice.
AB  - Harnessing the natural ability of viruses to infect post-mitotic cells such as
      neurons has provided an explosion of new methods to manipulate and reconstruct
      neural circuits in vivo. Here we describe the use of recombinant adeno-associated
      viral vectors (rAAV) for axonal tract tracing in nontransgenic and transgenic Cre
      driver mice. Two protocols are presented for stereotactic-guided placement of
      rAAV vectors into the live mouse brain using iontophoretic or nanoliter pressure
      injections. The methods discussed here will result in expression of fluorescent
      proteins in cell bodies, dendrites, and axons in targeted neurons, and can be
      easily adapted to address various experimental questions.

PMID- 22470148
TI  - Characterizing synaptic vesicle proteins using synaptosomal fractions and
      cultured hippocampal neurons.
AB  - Cloning and characterization of synaptic vesicle proteins and their binding
      counterparts on the presynaptic plasma membrane have greatly advanced our
      understanding of the molecular mechanisms involved in the synaptic vesicle cycle
      and neurotransmitter release. This unit discusses multidisciplinary approaches to
      characterize proteins from synaptosome-enriched subcellular fractions and
      localize them within cultured neurons. The first approach regroups methods used
      to isolate synaptic vesicles from rat brain synaptosomal preparations, allowing
      for specific biochemical investigation of synaptic vesicle proteins. The second
      is a detailed procedure for pre-embedding immunogold staining and electron
      microscopic observation, which permits the morphological identification of
      proteins in individual vesicles at intact synapses. Additionally, this chapter
      proposes methods for light microscopic examination of hippocampal neurons. It
      includes procedures for embryonic and postnatal hippocampal neuron culture and
      describes an immunocytochemical staining protocol used to investigate synaptic
      vesicle protein localization with respect to other proteins or subcellular
      structures.

PMID- 22470149
TI  - Culturing embryonic nasal explants for developmental and physiological study.
AB  - Primary cultures obtained from embryonic nasal placodes can maintain olfactory
      neurons, olfactory ensheathing cells, and large numbers of gonadotropin releasing
      hormone-1 (GnRH) neurons. Depending on the age of the starting material, one can
      examine cell interactions important for placode formation or neuronal migration
      and axonal outgrowth. When generated at E11.5 in mouse, neuronal migration and
      axon outgrowth away from the main tissue mass occurs. This area of the explant,
      the periphery, is only a few cells thick. This characteristic offers the
      opportunity to image single cells and axons and allows pharmacological and
      molecular manipulations as well as physiological recordings to be performed.
      Here, we describe a system for culturing nasal explants used in our laboratory.
      This model system provides a method for obtaining physiological cellular
      responses with post hoc immunohistochemistry, or gene expression studies, on
      cells arising from the nasal placode.

PMID- 22470151
TI  - Diet-induced models of obesity (DIO) in rodents.
AB  - Obesity results from a complex interplay between a susceptible genotype and an
      environment that both promotes increased caloric intake and enables sustained
      decreases in energy expenditure. One commonly employed approach to modeling
      obesity in preclinical species is the diet-induced obese (DIO) rodent. Here,
      theoretical and practical considerations for producing obese rodents via dietary
      manipulation, and for assessing drug-induced changes in food intake and body
      weight are described. Based on these considerations, a standardized protocol for
      diet-induced obesity in both mouse and rat is provided and sample data from these
      models are also described.

PMID- 22470150
TI  - A protein cross-linking assay for measuring cell surface expression of glutamate
      receptor subunits in the rodent brain after in vivo treatments.
AB  - Trafficking of neurotransmitter receptors between intracellular and cell surface
      compartments is important for regulating neurotransmission. We developed a method
      for determining if an in vivo treatment has altered receptor distribution in a
      particular region of rodent brain. After the treatment, brain slices are rapidly
      prepared from the region of interest. Then, cell surface-expressed proteins are
      covalently cross-linked using the membrane-impermeable, bifunctional cross-linker
      bis(sulfosuccinimidyl)suberate (BS(3)). This increases the apparent molecular
      weight of surface receptors, while intracellular receptors are not modified.
      Thus, surface and intracellular receptor pools can be separated and quantified
      using SDS-PAGE and immunoblotting. This method is particularly useful for
      analyzing AMPA receptor subunits, offering advantages in accuracy, efficiency,
      and cost compared to biotinylation. A disadvantage is that some antibodies no
      longer recognize their target protein after cross-linking. We have used this
      method to quantify changes in receptor distribution after acute and chronic
      exposure to psychomotor stimulants.

PMID- 22470152
TI  - Fountain flow cytometry.
AB  - Fountain Flow Cytometry (FFC) is a simple and inexpensive technology that is
      adaptable to situations requiring detection and enumeration of cells/organisms at
      low concentrations, but is limited to particles of relatively high fluorescence
      intensity. This work presents the basic physics behind the novel scheme Fountain
      Flow Cytometry employs for the detection of target particles, a hybrid of
      conventional flow cytometry and video epifluorescence microscopy. The method is
      based on LED-induced fluorescence of labeled particles and requires no filtration
      step. Unlike conventional flow cytometry, the resulting fluorescence is measured
      with a digital camera as the measured sample flows toward the camera along the
      optical axis. An automated target particle recognition and enumeration computer
      program, Biocount, is used to count particles. FFC allows for detection of target
      particles in transparent and translucent fluids, such as environmental water,
      blood, and beverages. In addition, FFC can be used for detection of target
      particles in the presence of high photometric background, including unbound
      fluorescent dye. This facilitates use of the technique in situations where cells
      are unwashed. Current applications extend, but are not limited to, particles from
      um-size bacteria to multi-millimeter-sized multicellular organisms.

PMID- 22470153
TI  - Two-photon imaging of the immune system.
AB  - Two-photon microscopy is a powerful method for visualizing biological processes
      as they occur in their native environment in real time. The immune system
      uniquely benefits from this technology as most of its constituent cells are
      highly motile and interact extensively with each other and with the environment.
      Two-photon microscopy has provided many novel insights into the dynamics of the
      development and function of the immune system that could not have been deduced by
      other methods and has become an indispensible tool in the arsenal of
      immunologists. In this unit, we provide several protocols for preparation of
      various organs for imaging by two-photon microscopy that are intended to
      introduce the new user to some basic aspects of this method.

PMID- 22470155
TI  - Live imaging of the lung.
AB  - Live imaging is critical to determining the dynamics and spatial interactions of
      cells within the tissue environment. In the lung, this has proven to be difficult
      due to the motion incurred by ventilation and cardiac contractions. In this
      chapter, we report protocols for imaging ex vivo live lung slices and the intact
      mouse lung.

PMID- 22470156
TI  - Exhaled nitric oxide measurement in patients affected by nasal polyposis.
AB  - OBJECTIVES: Nitric oxide (NO) is produced in the respiratory tract with a major
      contribution coming from paranasal sinuses and the nose. The pathophysiological
      role of NO in the airways has been debated. The aims of this study were to
      measure fraction of exhaled NO (FENO), a validated marker of airway inflammation,
      in patients affected by nasal polyposis with and without asthma; to assess the
      importance of FENO measurement in detecting subclinical involvement of lower
      airways in patients with clinical rhinosinusal symptoms; and to clarify the
      impact of endoscopic surgical removal of polyps on airway inflammation. SETTING:
      The study was conducted at the O.R.L. Clinic and Clinical Pharmacology Unit,
      University Hospital Agostino Gemelli, Rome, Italy. STUDY DESIGN: Prospective
      study. SUBJECTS AND METHODS: Concentrations of FENO were measured with the NIOX
      system (Aerocrine, Stockholm, Sweden) by using a single-breath online method,
      according to the American Thoracic Society guidelines. RESULTS: Compared with
      those in healthy subjects (15 [11-19] ppb, n = 15; P < .0001), FENO values were
      elevated in patients with nasal polyposis (41 [21-77] ppb, n = 43). There was no
      significant difference in FENO concentrations between asthmatic and nonasthmatic
      patients with nasal polyposis (P = .73). Concentrations of FENO in patients with
      nasal polyposis were decreased after surgery (64.2 [30.0-132.7] ppb vs 56.0 [26.4
      73.8] ppb, respectively; P = .03). CONCLUSION: The fraction of exhaled NO is
      elevated in the inflammatory process involving both the rhinosinusal district and
      lower airways, supporting the one-airway disease hypothesis.

PMID- 22470154
TI  - Near-infrared molecular probes for in vivo imaging.
AB  - Cellular and tissue imaging in the near-infrared (NIR) wavelengths between 700
      and 900 nm is advantageous for in vivo imaging because of the low absorption of
      biological molecules in this region. This unit presents protocols for small
      animal imaging using planar and fluorescence lifetime imaging techniques.
      Included is an overview of NIR fluorescence imaging of cells and small animals
      using NIR organic fluorophores, nanoparticles, and multimodal imaging probes. The
      development, advantages, and application of NIR fluorescent probes that have been
      used for in vivo imaging are also summarized. The use of NIR agents in
      conjunction with visible dyes and considerations in selecting imaging agents are
      discussed. We conclude with practical considerations for the use of these dyes in
      cell and small animal imaging applications.

PMID- 22470157
TI  - Graduated endoscopic multiangle approach for access to the infratemporal fossa: a
      cadaveric study with clinical correlates.
AB  - OBJECTIVE: The infratemporal fossa (ITF) has historically been one of the most
      difficult regions of the skull base to access surgically. Available open
      approaches are complex, are associated with high morbidity, and do not always
      afford optimal visualization. Endoscopic access to the ITF improves visualization
      for management of many sinonasal and lateral skull base lesions involving this
      region. The purpose of this study is to evaluate a graduated multiangle approach
      for endoscopic access to this area using a cadaveric model. STUDY DESIGN AND
      SETTING: Cadaveric study at an academic medical center. METHODS: Endoscopic
      dissection was performed on a total of 10 sides of 5 fresh cadaveric heads. Four
      different approaches to the ITF were studied: ipsilateral endonasal,
      endoscopically assisted Caldwell-Luc, contralateral endonasal via septotomy, and
      endoscopically assisted Gillies transtemporal. High-quality endoscopic pictures
      and high-definition videos of each technique were obtained in order to document
      the differences in access achieved with each approach. RESULTS: The combination
      of the 4 different endoscopic techniques allowed complete access to all areas of
      the ITF. The endoscopically assisted Caldwell-Luc improved anteroposterior
      access, the contralateral septotomy approach resulted in excellent far lateral
      access, and the endoscopically assisted Gillies approach allowed posterosuperior
      visualization and instrumentation. CONCLUSION: Endoscopic access to the ITF can
      be accomplished by each of the 4 methods described. A multiangle, graduated
      approach can provide surgeons the ability to customize surgical access depending
      on the location of a specific lesion within the ITF.

PMID- 22470158
TI  - Quantitative crawling wave sonoelastography of benign and malignant thyroid
      nodules.
AB  - OBJECTIVE: The purpose of this study is to determine if crawling wave
      elastography, a novel sonoelastography technique, can be used to provide
      quantitative measurements of thyroid tissue shear velocity (a measure of tissue
      stiffness) and distinguish between benign and malignant thyroid nodules. STUDY
      DESIGN: Diagnostic test assessment. SETTING: Academic university. SUBJECTS AND
      METHODS: Fresh thyroid specimens (n = 20) with 44 regions of interest were imaged
      ex vivo with crawling wave sonoelastography over a 9-month period in 2010 at a
      single institution. Using the sonoelastography technique, shear velocity
      estimations and contrast-to-noise ratios were calculated. The higher the shear
      velocity (SV) and contrast-to-noise ratio (CNR), the greater the tissue
      stiffness. Histological diagnosis was correlated with shear velocity and contrast
      to-noise ratio values. RESULTS: Both the shear velocity and contrast-to-noise
      values of papillary thyroid carcinoma (n = 10, CNR = 5.29, SV = 2.45 m/s) were
      significantly higher than benign nodules (n = 22, CNR = -0.41, SV = 1.90 m/s).
      There is a maximum sensitivity and specificity of 100% and 90.9%, respectively,
      for differentiating papillary thyroid carcinoma from benign nodules using
      contrast-to-noise ratio values. There is a maximum sensitivity and specificity of
      83.3% and 72.7%, respectively, for differentiating papillary thyroid carcinoma
      from benign nodules using shear velocity values. Insufficient samples were
      obtained for comparison with other histological types. CONCLUSION: Crawling wave
      sonoelastography can provide quantitative estimations of shear velocity, thereby
      depicting the elastic properties of thyroid nodules. The shear velocity and
      contrast-to-noise ratio can differentiate between benign thyroid nodules and
      papillary thyroid carcinoma with high specificity and sensitivity.

PMID- 22470159
TI  - Removal of biofilms from tracheoesophageal speech valves using a novel marine
      microbial deoxyribonuclease.
AB  - OBJECTIVE: The growth of biofilms on tracheoesophageal speech valves shortens
      their life span and produces a reservoir of pathogens that may infect the
      respiratory tract. The authors have discovered a novel nontoxic
      deoxyribonuclease, NucB, from a marine isolate of Bacillus licheniformis that is
      effective at dispersing a variety of mono and mixed-species bacterial biofilms.
      The aim of this preliminary study was to determine whether NucB could also
      disrupt and remove mixed-species biofilms from tracheoesophageal speech valves.
      STUDY DESIGN: Laboratory-based treatment and analysis of discarded
      tracheoesophageal speech valves. SETTING: University human biology laboratory and
      the Department of Speech and Language Therapy at a tertiary referral hospital.
      SUBJECTS AND METHODS: Seventeen ex vivo tracheoesophageal speech valves fouled
      with natural human biofilms were collected and divided into 2 equal parts. One
      half was treated with NucB and the other half with a control buffer solution.
      Biofilm removal was measured by microscopy and by culture of dispersed biofilm
      organisms on agar plates. RESULTS: Significantly more organisms were released
      from biofilms using NucB than with buffer solution alone. On nonselective medium,
      more organisms were cultured in 11 samples (65%, n = 17, P < .05). Using growth
      media favoring fungi, more organisms were cultured in 14 samples (82%, n = 17, P
      < .05). CONCLUSION: The nontoxic deoxyribonuclease NucB was effective in
      releasing more microorganisms from biofilms on tracheoesophageal speech valves.
      This reflects its potential ability to break up and disperse these biofilms.
      Future studies will aim to develop NucB as a novel agent to prolong the life span
      of tracheoesophageal speech valves, thus reducing health care costs.

PMID- 22470160
TI  - Integrative analysis in oral squamous cell carcinoma reveals DNA copy number
      associated miRNAs dysregulating target genes.
AB  - OBJECTIVE: To better understand possible mechanisms involved in the dysregulation
      of gene expression unique to oral squamous cell carcinoma (OSCC) metastasis, the
      investigators examined the differential expression of microRNAs (miRNAs) in OSCC
      metastasis and their functional impact on target gene expression. STUDY DESIGN:
      Observational assessment of DNA copy number, miRNA, and RNA expression in primary
      and metastatic OSCC. SETTING: University of Washington Medical Center and
      affiliated hospitals. SUBJECTS: Tumor samples were taken from patients with
      primary incident OSCC; cells were laser-capture microdissected from 17
      nonmetastatic primary tumors and 20 metastatic lymph nodes. METHODS: DNA copy
      number aberrations and gene expression profiles were previously determined using
      Affymetrix 250K Nsp I SNP arrays and HU133 plus 2.0 expression arrays. miRNAs
      were interrogated with Exiqon's Ready-to-Use PCR Panels assessing the expression
      of 368 human miRNAs. RESULTS: Investigators found 31 miRNAs differentially
      expressed between metastatic and nonmetastatic samples (false discovery rate
      <0.4; 26 overexpressed and 5 underexpressed in metastatic samples). Expression of
      7 of these miRNAs was significantly associated with their DNA copy numbers, and
      expressions of 8 of these miRNAs were significantly associated with their target
      genes. Among these unique miRNAs, miR-140-3p, miR-29c, and miR-29a were
      differentially expressed in metastasis versus nonmetastatic samples and had a
      strong positive correlation with their DNA copy numbers and a negative
      correlation with the expression of their target genes. CONCLUSION: Results
      suggest that DNA copy number aberration may play a role in the dysregulation of
      some differentially expressed miRNAs in OSCC metastasis, warranting further
      investigation.

PMID- 22470161
TI  - UK Biobank opens it data vaults to researchers.

PMID- 22470162
TI  - US regulator seeks advice on health risks of metal on metal hip implants.

PMID- 22470163
TI  - Drug firms may be spending as much as ?91m a year on lobbying in Europe.

PMID- 22470164
TI  - Immune surveillance of senescent cells--biological significance in cancer- and
      non-cancer pathologies.
AB  - Cellular senescence, a state of stable growth arrest, can occur in response to
      various stress stimuli such as telomere shortening, treatment with
      chemotherapeutic drugs or the aberrant activation of oncogenes. Senescent cells
      communicate with their environment by secreting various cytokines and growth
      factors, and it has become clear that this 'secretory phenotype' can have pro- as
      well as anti-tumorigenic effects. Recent work from our laboratory showed that
      premalignant, senescent hepatocytes are recognized and cleared through an antigen
      specific immune response and that this immune response, designated as 'senescence
      surveillance' is crucial for tumor suppression in the liver [(Kang,T.W. et al.
      (2011) Senescence surveillance of pre-malignant hepatocytes limits liver cancer
      development. Nature, 479, 547-551]. It is an emerging concept that immune
      responses against senescent cells have a broader biological significance in
      cancer- as well as non-cancer pathologies and current data suggest that distinct
      immune responses are engaged to clear senescent cells in different disease
      settings. In this review article, we will discuss different examples how immune
      responses against senescent cells are involved to restrict disease progression in
      cancer- and non-cancer pathologies.

PMID- 22470165
TI  - Oral lichen planus.

PMID- 22470168
TI  - Changing patterns in suicide among young people.

PMID- 22470167
TI  - Fever and multiorgan infarcts in a 35-year-old man.

PMID- 22470169
TI  - Inflammatory ocular adverse events with the use of oral bisphosphonates: a
      retrospective cohort study.
AB  - BACKGROUND: There have been several published reports of inflammatory ocular
      adverse events, mainly uveitis and scleritis, among patients taking oral
      bisphosphonates. We examined the risk of these adverse events in a
      pharmacoepidemiologic cohort study. METHODS: We conducted a retrospective cohort
      study involving residents of British Columbia who had visited an ophthalmologist
      from 2000 to 2007. Within the cohort, we identified all people who were first
      time users of oral bisphosphonates and who were followed to the first
      inflammatory ocular adverse event, death, termination of insurance or the end of
      the study period. We defined an inflammatory ocular adverse event as scleritis or
      uveitis. We used a Cox proportional hazard model to determine the adjusted rate
      ratios. As a sensitivity analysis, we performed a propensity-score-adjusted
      analysis. RESULTS: The cohort comprised 934,147 people, including 10,827 first
      time users of bisphosphonates and 923,320 nonusers. The incidence rate among
      first-time users was 29/10,000 person-years for uveitis and 63/10,000 person
      years for scleritis. In contrast, the incidence among people who did not use oral
      bisphosphonates was 20/10,000 person-years for uveitis and 36/10,000 for
      scleritis (number needed to harm: 1100 and 370, respectively). First-time users
      had an elevated risk of uveitis (adjusted relative risk [RR] 1.45, 95% confidence
      interval [CI] 1.25-1.68) and scleritis (adjusted RR 1.51, 95% CI 1.34-1.68). The
      rate ratio for the propensity-score-adjusted analysis did not change the results
      (uveitis: RR 1.50, 95% CI 1.29-1.73; scleritis: RR 1.53, 95% CI 1.39-1.70).
      INTERPRETATION: People using oral bisphosphonates for the first time may be at a
      higher risk of scleritis and uveitis compared to people with no bisphosphonate
      use. Patients taking bisphosphonates must be familiar with the signs and symptoms
      of these conditions, so that they can immediately seek assessment by an
      ophthalmologist.

PMID- 22470170
TI  - Everything in moderation, including vision.

PMID- 22470172
TI  - Suicide among children and adolescents in Canada: trends and sex differences,
      1980-2008.
AB  - BACKGROUND: Suicide is the second leading cause of death for young Canadians (10
      19 years of age)--a disturbing trend that has shown little improvement in recent
      years. Our objective was to examine suicide trends among Canadian children and
      adolescents. METHODS: We conducted a retrospective analysis of standardized
      suicide rates using Statistics Canada mortality data for the period spanning from
      1980 to 2008. We analyzed the data by sex and by suicide method over time for two
      age groups: 10-14 year olds (children) and 15-19 year olds (adolescents). We
      quantified annual trends by calculating the average annual percent change (AAPC).
      RESULTS: We found an average annual decrease of 1.0% (95% confidence interval
      [CI] -1.5 to -0.4) in the suicide rate for children and adolescents, but
      stratification by age and sex showed significant variation. We saw an increase in
      suicide by suffocation among female children (AAPC = 8.1%, 95% CI 6.0 to 10.4)
      and adolescents (AAPC = 8.0%, 95% CI 6.2 to 9.8). In addition, we noted a
      decrease in suicides involving poisoning and firearms during the study period.
      INTERPRETATION: Our results show that suicide rates in Canada are increasing
      among female children and adolescents and decreasing among male children and
      adolescents. Limiting access to lethal means has some potential to mitigate risk.
      However, suffocation, which has become the predominant method for committing
      suicide for these age groups, is not amenable to this type of primary prevention.

PMID- 22470173
TI  - Obtaining sustenance through spirits.

PMID- 22470171
TI  - Initiating insulin in patients with type 2 diabetes.

PMID- 22470174
TI  - Former Supreme Court justice blasts minimum sentences for marijuana offenders.

PMID- 22470175
TI  - India moves to contain organ donation havoc.

PMID- 22470177
TI  - Graduated drivers' licences for seniors: reclaiming one benefit of being young.

PMID- 22470178
TI  - Feds target redundancies and waste at Health Canada.

PMID- 22470179
TI  - A national perspective on teachers' efficacy beliefs in deaf education.
AB  - Teachers' sense of efficacy, or the belief that teachers have of their capacity
      to make an impact on students' performance, is an unexplored construct in deaf
      education research. This study included data from 296 respondents to examine the
      relationship of teacher and school characteristics with teachers' sense of
      efficacy in 80 different deaf education settings in the US. Deaf education
      teachers reported high overall efficacy beliefs but significantly lower efficacy
      beliefs in the area of student engagement than in instructional strategies and
      classroom management. Teachers' years of experience showed a significant
      relationship with efficacy beliefs, yet it was the teachers' perceived collective
      efficacy of their educational setting that ultimately predicted teachers' sense
      of efficacy. These findings lend credence to the need for further examination of
      school processes that influence teacher beliefs and attitudes in deaf education
      settings.

PMID- 22470181
TI  - Belief.

PMID- 22470180
TI  - Parenting styles of mothers with deaf or hard-of-hearing children and hearing
      siblings.
AB  - The present study aims to determine whether rearing a deaf or hard-of-hearing
      (d/hh) child would differentiate the parenting and disciplinary preference of
      parents between the d/hh and the hearing child. The parenting styles of 30
      hearing mothers from Cyprus were assessed using the Greek version of the
      Parenting Styles & Dimensions Questionnaire. Additionally, mothers rated sibling
      interactions using the sibling inventory of behavior. The results indicated that
      the dominant parenting style for both the hearing and the d/hh children among the
      participating mothers was the authoritative type and the least prevalent parental
      types were the permissive and the strict. Moreover, mothers' perceptions of
      sibling relationship were found to be a significant factor in predicting mothers'
      reported parenting styles in this sample. The contribution of the present
      findings to our knowledge of the parenting characteristics and practices of
      families who have a d/hh child along with their possible implications for child
      and family services are discussed.

PMID- 22470182
TI  - Extraesophageal reflux is still NOT the same disorder as gastroesophageal reflux.

PMID- 22470185
TI  - [The role of the class A scavenger receptors, SR-A and MARCO, in the immune
      system. Part 1. The structure of receptors, their ligand binding repertoires and
      ability to initiate intracellular signaling].
AB  - Recognition of pathogens by innate immune cells is mediated by pattern
      recognition receptors (PRR), which include scavenger receptors (SR). The class A
      SR, SR-A/CD204 and MARCO, are characterized by the presence of collagenous and SR
      cysteine-rich domains in their extracellular portions. Both receptors are
      expressed mainly on macrophages and dendritic cells. Thanks to their ability to
      bind to a wide range of polyanionic ligands, the class A SR may participate in
      numerous functions of these cells, such as endocytosis, and adhesion to
      extracellular matrix and to other cells. Among SR-A ligands are oxidized
      lipoproteins and beta-amyloid fibrils, which link SR-A to the pathogenesis of
      arteriosclerosis and Alzheimer's disease. Despite the demonstration of class A SR
      involvement in so many processes, the lack of selective ligands precluded
      reaching definite conclusions concerning their signaling abilities. Using
      specific receptor ligation with antibodies, we showed that SR-A and MARCO trigger
      intracellular signaling, modulating pro-inflammatory and microbicidal activities
      of macrophages. Surprisingly, despite similarities in structure and ligand
      binding repertoires, SR-A and MARCO exert opposite effects on interleukin-12 (IL
      12) production in macrophages. SR-A ligation also stimulated H2O2 and IL-10
      production, but had no effect on the release of several other cytokines. These
      limited effects of specific SR-A ligation contrast with generalized enhancement
      of immune responses observed in SR-A-deficient mice. Recent studies have revealed
      that many of these effects of SR-A deficiency may be caused by compensatory
      changes in the expression of other receptors and/or disinhibition of signal
      transduction from receptors belonging to the Toll/IL-1R family, rather than by
      the loss of the receptor function of SR-A.

PMID- 22470186
TI  - [The role of the class A scavenger receptors, SR-A and MARCO, in the immune
      system. Part 2. Contribution to recognition and phagocytosis of pathogens as well
      as induction of immune response].
AB  - Recognition of pathogens by innate immune cells is mediated by pattern
      recognition receptors (PRR), which include the class A scavenger receptors (SR),
      SR-A/CD204 and MARCO. It seems that in addition to activating innate immune
      responses, phagocytosis and inflammation, this initial, PRR-mediated recognition
      also determines polarization of adaptive immune responses (Th1, Th2, Th17 or
      Treg). It has been demonstrated that class A SR are major PRR mediating opsonin
      independent phagocytosis. SR-A- or MARCO-deficient mice exhibit impaired ability
      to control bacterial infections, resulting in increased mortality. Our results
      suggest that in addition to impaired bacterial destruction by macrophages,
      dysregulation of immune responses may contribute to defective antibacterial
      defense in class A SR-deficient mice. Using specific receptor ligation with
      antibodies, we showed that SR-A and MARCO regulate in an opposite manner
      production of IL-12 in macrophages, the cytokine playing a crucial role in
      Th1/Th2 polarization of adaptive immune responses. Together with the observation
      that expression of MARCO is increased by different Th1-polarizing factors and
      decreased by Th2-polarizing factors, these results suggest that changes in
      relative expression levels of SR-A and MARCO may be a mechanism of sustained
      polarization of adaptive immune responses.

PMID- 22470187
TI  - Celery--cause of severe anaphylactic shock.
AB  - BACKGROUND: We present a case of anaphylactic shock induced by celery ingestion
      in a 28-year old woman with pollinosis during allergen (50% birch, 50% grass)
      immunotherapy. CASE REPORT: A female patient, aged 28 was admitted to the clinic
      due to a serious anaphylactic reaction. The event took place 15 min after
      ingesting fresh celery. She recovered after routine treatment with adrenaline,
      corticosteroids and antazoline. CONCLUSIONS: Our case shows the possibility of
      simultaneous occurrence of hypersensitivity to inhaled allergens and food. In
      such cases, it is considered part of cross-reactivity We discuss the importance
      of cross- reactivity associated with sensitization to pollen and vegetable foods.

PMID- 22470188
TI  - [Pleiotropic action of proinsulin C-peptide].
AB  - Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic
      beta cells, since its discovery in 1967 has been thought to be devoid of
      biological functions apart from correct insulin processing and formation of
      disulfide bonds between A and B chains. However, in the last two decades research
      has brought a substantial amount of data indicating a crucial role of C-peptide
      in regulating various processes in different types of cells and organs. C-peptide
      acts presumably via either G-protein-coupled receptor or directly inside the
      cell, after being internalized. However, a receptor binding this peptide has not
      been identified yet. This peptide ameliorates pathological changes induced by
      type 1 diabetes mellitus, including glomerular hyperfiltration, vessel
      endothelium inflammation and neuron demyelinization. In diabetic patients and
      diabetic animal models, C-peptide substitution in physiological doses improves
      the functional and structural properties of peripheral neurons and protects
      against hyperglycemia-induced apoptosis, promoting neuronal development,
      regeneration and cell survival. Moreover, it affects glycogen synthesis in
      skeletal muscles. In vitro C-peptide promotes disaggregation of insulin
      oligomers, thus enhancing its bioavailability and effects on metabolism. There
      are controversies concerning the biological action of C-peptide, particularly
      with respect to its effect on Na+/K+-ATPase activity. Surprisingly, the excess of
      circulating peptide associated with diabetes type 2 contributes to
      atherosclerosis development. In view of these observations, long-term, large
      scale clinical investigations using C-peptide physiological doses need to be
      conducted in order to determine safety and health outcomes of long-term
      administration of C-peptide to diabetic patients.

PMID- 22470190
TI  - Surgical excision of extensive anal condylomata is a safe operation without risk
      of anal stenosis.
AB  - INTRODUCTION: Anal condylomata acuminata was a well-known disease in ancient
      times but in recent years there has been a rapidly increasing number of people
      who suffer from this disease. The main cause of this disease is infection of
      human papilloma virus (HPV) which occurs through sexual contact. Currently there
      are three different ways to treat anal condylomata. Small changes of anal
      condylomata can be treated with local therapeutic agents, but the best results of
      treatment of extensive changes are obtained by surgical techniques.
      MATERIAL/METHODS: The study group consisted of 30 patients with diagnosed
      extensive anal condylomata who underwent surgery in Mikolaj Pirogow High
      Specialized Hospital in Lodz. The survey was conducted from 2007 to 2011.
      Patients had been directed to the surgical ward by general surgeons and
      practitioners, proctologists and urologists. The diagnosis was made after
      proctological assessment in the knee-chest position. RESULTS: All patients
      underwent surgery and had complete macroscopic electroexcision of anal
      condylomata. In the research group there was no mortality. Postoperative
      complications occurred in 4 (13.3%) patients--postoperative bleeding. Strong pain
      was present in 14 (46.7%) patients but only in the postoperative period. During
      postoperative follow-up there was no observed infection in the anal region or
      recurrence of disease. In the operated group there were no observed cosmetic
      deformations of the anus and/or the anal canal, narrow anal canal or functional
      fecal incontinence symptoms. CONCLUSIONS: Surgical treatment of anal condylomata
      is an effective and safe method for the patient. In our research there were no
      serious postoperative complications or recurrence of the disease during the
      follow-up period.

PMID- 22470189
TI  - The antiradical activity of some plant raw materials and extracts obtained from
      these raw materials.
AB  - INTRODUCTION: Free radicals and reactive oxygen species are compounds usually
      present in healthy organisms as natural products of many metabolic pathways, and
      they are important in cell signaling and homeostasis. As a source of reactive
      oxygen species one can mention phagocytic cells and enzymes such as xanthine
      oxidase. Sometimes the level of reactive oxygen species strongly increases. This
      may lead to damage of very important cell structures such as nucleic acids,
      proteins or lipids. In this situation one should provide the organism with
      powerful antioxidants as a medicine or in the diet. A rich source of strong
      antioxidants such as phenolic compounds is plant raw materials, which are the
      subject of our study. MATERIAL/METHODS: Antiradical potential of extracts was
      measured with DPPH radical (2,2-diphenyl-1-picrylhydrazyl) and was expressed as
      the number of units per mg of extracts (TAU(515/mg)) and per g of raw material
      (TAU(515/g)). The amount of phenolic compounds was determined colorimetrically
      using Folin-Ciocalteu phenol reagent (3H2O * P2O5 * 13WO3 * 5MoO3 * 10H2O).
      RESULTS: The strongest antiradical activity was noted for extracts obtained from
      Cinnamomi cortex; the number of antiradical units per mg of extract (TAU(515/mg))
      was 10.31+/-1.052. The lowest antiradical features were exhibited by extract from
      Zingiberis rhizoma (0.28+/-0.174) and extract from Cichorii radix (0.38+/-0.669).
      The highest amount of phenolic compounds was measured for extracts from Bistortae
      rhizoma, with a value (in percentage) of 78.6+/-13.5. The correlation coefficient
      between the number of antiradical units in extracts and amount of phenolic
      compounds in these extracts was 0.7273. When the number of antiradical units was
      calculated per g of raw material (TAU(515/g)) the strongest antiradical
      properties were noted for Bistortae rhizoma (1406+/-274.9), the weakest for
      Cichorii radix (122+/-158.3).

PMID- 22470191
TI  - [The role of the ERM protein family in maintaining cellular polarity, adhesion
      and regulation of cell motility].
AB  - Ezrin, radixin and moesin, forming the ERM protein family, act as molecular
      crosslinkers between actin filaments and proteins anchored in the cell membrane.
      By participating in a complex intracellular network of signal transduction
      pathways, ERM proteins play a key role in the regulation of adhesion and polarity
      of normal cells through interactions with membrane molecules, e.g. E-cadherin.
      Dynamic cytoskeletal transformations, in which the ERM and Rho GTPases are
      involved, lead to the formation of membrane-cytoplasmic structures, such as
      filopodia and lamellipodia, which are responsible for cellular motility. The
      interactions of ERM proteins with active Akt kinase cause the acquisition of
      antiapoptotic cellular features by downregulation of the proapoptotic protein
      Bad. ERM protein activity is regulated by phosphorylation/dephosphorylation
      reactions and linking phosphatidylinositols. The model of activation based on the
      molecular conformation changes by breaking the intramolecular bonds and exposing
      actin binding sites is essential for the proper functioning of the ERM proteins.
      Additionally, the connection types between the ERM and membrane proteins (direct
      or indirect by EBP50 and E3KARP) play an important role in transduction of
      signals from the extracellular matrix. Due to the wide range of ezrin, radixin
      and moesin cytophysiological features, detailed exploration of the ERM
      biochemistry will provide a series of answers to questions about ambiguous
      functions in many intracellular signal transduction pathways.

PMID- 22470192
TI  - [The role of glucose transporter 1 (GLUT1) in the diagnosis and therapy of
      tumors].
AB  - Malignant cells are known to enhance glucose metabolism, to increase glucose
      uptake and to inhibit the process of oxidative phosphorylation. Accelerated
      glycolysis is one of the biochemical characteristics of cancer cells that allow
      them to compensate the inefficient extraction of energy from glucose in order to
      continue their uncontrolled growth and proliferation. Upregulation of glucose
      transport across the plasma membrane is mediated by a family of facilitated
      glucose transporter proteins named GLUT. Overexpression of GLUTs, especially the
      hypoxia-responsive GLUT1, has been frequently observed in various human
      carcinomas. Many studies have reported a correlation between GLUT1 expression
      level and the grade of tumor aggressiveness, which suggests that GLUT1 expression
      may be of prognostic significance. Therefore, GLUT1 is a key rate-limiting factor
      in the transport and glucose metabolism in cancer cells. This paper presents the
      current state of knowledge on GLUT1 regulation as well as its utility in the
      diagnosis and therapy of cancers.

PMID- 22470193
TI  - Is serum cystatin C a better marker of kidney function than serum creatinine in
      septic newborns?
AB  - INTRODUCTION: Several studies have claimed that the estimation of serum cystatin
      C could be a better marker of kidney excretory function than serum creatinine.
      However, its role in the diagnosis of reduced kidney function was not
      unquestionably confirmed. The aim of this study was to analyze the concentrations
      of serum cystatin C in neonates with sepsis. MATERIAL/METHODS: Thirty-two
      neonates (gestational age from 34 to 40 weeks) admitted to the NICU during the
      first 14 days of life were enrolled. Serum cystatin C concentrations were
      estimated by ELISA during three successive days in neonates treated for
      infection. The study group consisted of 9 newborns with sepsis, 14 with severe
      sepsis and 9 with septic shock. RESULTS/DISCUSSION: At the beginning of the
      observational period the mean serum concentration of cystatin C in the study
      group was 1.35 mg/L (95% CI 1.20-1.49). Surprisingly, the lowest concentration of
      cystatin was observed in patients with septic shock (1.23 mg/L; 95%CI 0.92-1.54)
      within the observation period. Higher concentrations were found in neonates with
      sepsis (1.47 mg/L; 95%CI 1.04-1.90) and severe sepsis (1.50; 1.12-1.87). There
      was no correlation between serum cystatin C concentration and serum creatinine or
      gestational age. A significant correlation was discovered between chronological
      age and cystatin C (R=-0.439, p=0.01). There was a tendency for cystatin C to
      decline during the second observational day in patients with sepsis (to 1.53
      mg/L; 95%CI: 1.19-1.86) and severe sepsis (to 1.32 mg/L; 95%CI: 1.07-1.57), while
      a slight insignificant increase in patient with septic shock (to 1.28 mg/L;
      95%CI: 0.88-1.68) was revealed. The interrelation between age and cystatin C
      concentration disappeared in the following days of stay in the NICU. Even in
      patients who died in the course of septic shock the observed changes in cystatin
      C levels were small and did not exceed those of serum creatinine. CONCLUSIONS:
      Cystatin C is not a useful marker of kidney function in neonates with sepsis.

PMID- 22470195
TI  - Alkylresorcinol metabolites in urine correlate with the intake of whole grains
      and cereal fibre in free-living Swedish adults.
AB  - Alkylresorcinols (AR) have been established as short/medium-term biomarkers for
      whole grain (WG) wheat and rye intake; and AR metabolites, 3,5-dihydroxybenzoic
      acid and 3-(3,5-dihydroxyphenyl)-propanoic acid, have been suggested as
      complementary biomarkers to AR. The present study examined the medium-term
      reproducibility and relative validity of urinary AR metabolites as biomarkers for
      WG and cereal fibre intake. A total of sixty-six free-living Swedes completed 3 d
      weighed food records and provided single 24 h urine collections and morning urine
      spot samples on two occasions, 2-3 months apart. The medium-term reproducibility
      of urinary AR metabolites was moderate when assessed in 24 h collections and
      lower in creatinine (CR)-adjusted morning urine. Mean AR metabolite 24 h
      excretions correlated well with total WG (r(s) 0.31-0.52, P < 0.05) and cereal
      fibre (r(s) 0.46-0.58, P < 0.001) intake on both occasions. As expected,
      correlations with WG (r(s) 0.28-0.38, P < 0.05) and cereal fibre (r(s) 0.35-0.42,
      P < 0.01) were weaker for mean CR-adjusted AR metabolite concentrations in spot
      samples of morning urine, although the adjusted concentrations correlated well
      with 24 h urinary excretion (r(s) 0.69-0.73, P < 0.001). Adjustment for intra
      individual variations substantially improved the correlations between intake and
      excretion. These findings suggest that urinary AR metabolites can successfully
      reflect the medium-term intake of WG and cereal fibre when adjusted for intra
      individual variation in this population, where rye was the major contributor to
      high WG intake. The performance of urinary AR metabolites as medium-term
      biomarkers appears to be comparable to that of fasting plasma AR concentration in
      this population.

PMID- 22470198
TI  - Prelude.

PMID- 22470196
TI  - Stratification of Wilms tumor by genetic and epigenetic analysis.
AB  - Somatic defects at five loci, WT1, CTNNB1, WTX, TP53 and the imprinted 11p15
      region, are implicated in Wilms tumor, the commonest childhood kidney cancer. In
      this study we analysed all five loci in 120 Wilms tumors. We identified
      epigenetic 11p15 abnormalities in 69% of tumors, 37% were H19 epimutations and
      32% were paternal uniparental disomy (pUPD). We identified mutations of WTX in
      32%, CTNNB1 in 15%, WT1 in 12% and TP53 in 5% of tumors. We identified several
      significant associations: between 11p15 and WTX (P=0.007), between WT1 and CTNNB1
      (P less than 0.001), between WT1 and pUPD 11p15 (P=0.01), and a strong negative
      association between WT1 and H19 epimutation (P less than 0.001). We next used
      these data to stratify Wilms tumor into three molecular Groups, based on the
      status at 11p15 and WT1. Group 1 tumors (63%) were defined as 11p15-mutant and
      WT1-normal; a third also had WTX mutations. Group 2 tumors (13%) were WT1-mutant.
      They either had 11p15 pUPD or were 11p15-normal. Almost all had CTNNB1 mutations
      but none had H19 epimutation. Group 3 tumors (25%) were defined as 11p15-normal
      and WT1-normal and were typically normal at all five loci (P less than 0.001). We
      also identified a novel clinical association between H19 epimutation and
      bilateral disease (P less than 0.001). These data provide new insights into the
      pattern, order, interactions and clinical associations of molecular events in
      Wilms tumor.

PMID- 22470194
TI  - Targeted therapy for hepatocellular carcinoma: novel agents on the horizon.
AB  - Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for
      90% of primary liver cancers. In the last decade it has become one of the most
      frequently occurring tumors worldwide and is also considered to be the most
      lethal of the cancer systems, accounting for approximately one third of all
      malignancies. Although the clinical diagnosis and management of early-stage HCC
      has improved significantly, HCC prognosis is still extremely poor. Furthermore,
      advanced HCC is a highly aggressive tumor with a poor or no response to common
      therapies. Therefore, new effective and well-tolerated therapy strategies are
      urgently needed. Targeted therapies have entered the field of anti-neoplastic
      treatment and are being used on their own or in combination with conventional
      chemotherapy drugs. Molecular-targeted therapy holds great promise in the
      treatment of HCC. A new therapeutic opportunity for advanced HCC is the use of
      sorafenib (Nexavar). On the basis of the recent large randomized phase III study,
      the Sorafenib HCC Assessment Randomized Protocol (SHARP), sorafenib has been
      approved by the FDA for the treatment of advanced HCC. Sorafenib showed to be
      able to significantly increase survival in patients with advanced HCC,
      establishing a new standard of care. Despite this promising breakthrough,
      patients with HCC still have a dismal prognosis, as it is currently the major
      cause of death in cirrhotic patients. Nevertheless, the successful results of the
      SHARP trial underscore the need for a comprehensive understanding of the
      molecular pathogenesis of this devastating disease. In this review we summarize
      the most important studies on the signaling pathways implicated in the
      pathogenesis of HCC, as well as the newest emerging drugs and their potential use
      in HCC management.

PMID- 22470197
TI  - Maturation of digestive function is retarded and plasma antioxidant capacity
      lowered in fully weaned low birth weight piglets.
AB  - The digestive function of low birth weight (LBW) pigs post-weaning has been
      poorly studied. Therefore, newborns from eleven hyperprolific sows were weighed,
      weaned at 27.2 d and fed a starter diet until sampling. Sampling was done between
      18 and 28 d post-weaning. An LBW piglet (n 19) was defined as a piglet having a
      birth weight less than 1 kg and less than the lower quartile of litter birth
      weights. Normal birth weight (NBW) piglets (n 13) were having a birth weight
      close to the mean litter birth weight. For each piglet, eighty-eight variables
      were determined. Data were analysed with linear models with type of piglet and
      litter as predictors. A principal component analysis was performed to determine
      the most important discriminating variables. In the LBW pig, the development of
      the digestive tract post-weaning was delayed: lower small-intestinal
      weight:length ratio due to a thinner tela submucosa and tunica muscularis and a
      higher secretory capacity, both in the distal jejunum. These observations might
      be a consequence of lower circulating insulin-like growth factor-1 (IGF-1)
      concentrations (126 (se 10.0) v. 158 (se 12.0) ng/ml for LBW and NBW,
      respectively) and a lower density of IGF-1 receptors in the proximal small
      intestine. Additionally, the plasma antioxidant capacity was lower for the LBW
      pig. Taken together, in the LBW piglet, the normal gut maturation post-weaning
      was retarded and this did not seem to be related to the weaning transition as
      such.

PMID- 22470199
TI  - VDRL test and its interpretation.
AB  - Venereal disease research laboratory (VDRL) test is a nontreponemal test, used
      for screening of syphilis due to its simplicity, sensitivity and low cost.
      Prozone phenomenon and biological false positive (BFP) reaction are two
      shortcomings of this test. Quantitative estimation of VDRL is essential in
      treatment evaluation. CSF VDRL test is very specific for neurosyphilis though its
      sensitivity is low. Interpretation of VDRL in HIV infection is incompletely
      understood.

PMID- 22470200
TI  - Allogenic hematopoietic stem cell transplantation in pemphigus vulgaris: a single
      center experience.
AB  - BACKGROUND: Pemphigus vulgaris (PV), an autoimmune disorder characterized by
      blistering skin/mucus membrane lesions, is mediated by desmoglein-3
      autoantibodies. We carried out a prospective clinical trial of hematopoietic stem
      cell transplantation (HSCT) in thymus, bone marrow (BM) and periphery to
      reconstitute central and peripheral arms of self-tolerance. MATERIALS AND
      METHODS: Eleven (M:F=5:6) patients with mean age 33.5 years and mean duration of
      disease 22.8 months, having painful pruritic blisters and ulcers resistant to
      corticosteroids, were treated with cytokine-stimulated allogeneic HSCT (mean
      dose: 21.8 * 10(8) cells/kg BW) from blood group-matched related donors. BM with
      mean CD34+ count 1.1% was inoculated into thymus, marrow and periphery, followed
      by two peripheral blood stem cell (PBSC) infusions. RESULTS: Recovery began
      within 24 hours of HSCT and new lesions stopped after 6 months. No graft versus
      host disease (GvHD)/adverse effect was observed in any patient/donor. Over a mean
      follow-up of 8.02 years, all patients were well without recurrence/new lesions.
      CONCLUSION: Drug-resistant PV can be successfully and safely treated by
      allogeneic HSCT.

PMID- 22470201
TI  - Serum concentration of IL-6, IL-2, TNF-alpha, and IFNgamma in Vitiligo patients.
AB  - BACKGROUND: Vitiligo is an acquired depigmenting disorder characterized by the
      loss of functional melanocytes from the epidermis. Although the etiology of
      vitiligo is unknown, over the last few years, substantial data from clinical
      research has greatly supported the 'Autoimmune theory' and this is supported by
      the frequent association of vitiligo with disorders that have an autoimmune
      origin, including Hashimoto's thyroiditis, Graves disease, type 1 insulin
      dependent diabetes mellitus, and Addison's disease. As cytokines are important
      mediators of immunity, there is evidence to suggest that they play a major role
      in the pathogenesis of autoimmune diseases. AIM: Keeping this in view we have
      assayed sera for cytokine IL-6, IL-2, Tumor necrosis factor (TNF)-alpha, and
      IFNgamma in 80 cases of vitiligo and compared it with healthy subjects, in order
      to find out whether they play a role in the pathogenesis of vitiligo or not.
      MATERIALS AND METHODS: Serum IL-6, IL-2, TNF-alpha, and IFNgamma were done by the
      indirect enzyme linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-6
      and IL-2 levels in the patient group were significantly higher when compared with
      those of the normal controls. The mean serum IFNgamma level in patients with
      vitiligo was significantly lower than that in the control group. There was no
      significant difference in the serum level of TNF-alpha between vitiligo and
      healthy controls. CONCLUSION: An increase in the production of proinflammatory
      cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role
      in melanocytic cytotoxicity. Thus, we speculate that the cytokine production of
      epidermal microenvironment may be involved in vitiligo.

PMID- 22470202
TI  - Generation and characterization of chicken egg yolk antibodies against
      propionibacterium acnes for the prevention of acne vulgaris.
AB  - INTRODUCTION: Antigen-specific antibody has been widely used for immunological
      analysis in the field of diagnosis as well as in pure scientific research, where
      the IgY antibodies can be raised against P acnes antigen. MATERIAL AND METHODS:
      To produce IgY against Propionibacterium acnes, laying hens were immunized with P
      acnes (MTCC No: 1951) and subsequent booster injections were given. The
      antibodies produced were purified from the egg yolk of immunized chicken using
      the polyethylene glycol and ammonium sulfate precipitation method and, further,
      by Diethylaminoethyl (DEAE) cellulose ion-exchange column chromatography. The
      protein fraction of IgY was isolated from the egg yolk. The separation was rapid,
      and the success of each step was viewed on Sodium Dodecyl Sulphate-polyacrylamide
      gel electrophoresis (SDS-PAGE). The reactivity of anti-P acnes was evaluated by
      the Enzyme-linked immunosorbent assay (ELISA) test and the dot-immunoassay.
      RESULTS: With ELISA, the highest titter of 1:10000 was observed on the 150(th)
      day after vaccination. The results of dot-immunoassay suggested that anti-P acnes
      IgY developed a brown color as positive reaction, which showed the antigen
      antibody binding even after a maximum dilution of 1/500. These results suggest
      that anti-acne IgY was produced and had strong specific antibody reactivity.
      CONCLUSION: The findings indicate that anti-acne IgY is worth utilizing as a
      preventive agent for acne vulgaris.

PMID- 22470203
TI  - A clinical study of dermatoses in diabetes to establish its markers.
AB  - BACKGROUND: Cutaneous manifestations of diabetes mellitus generally appear
      subsequent to the development of the disease, but they may be the first
      presenting signs and in some cases they may precede the primary disease
      manifestation by many years. AIMS: The aim of our study was to study the spectrum
      of dermatoses in diabetics, to know the frequency of dermatoses specific to
      diabetes mellitus (DM), and to establish the mucocutaneous markers of DM.
      MATERIAL AND METHODS: The study was conducted at a diabetic clinic and our
      department between September 2008 and June 2010. Two hundred and twenty-four
      diabetic patients were included in the study group and those with gestational
      diabetes were excluded. Healthy age- and sex-matched individuals were taken as
      controls. RESULTS: The male to female ratio was 1 : 1.21. Type 2 DM was seen in
      89.7% and type 1 DM in 10.3% of the patients. Dermatoses were seen in 88.3% of
      the diabetics compared to 36% in non-diabetic controls (P<0.05). Cutaneous
      infections were the most common dermatoses followed by acanthosis nigricans and
      xerosis in diabetics. Type 2 DM was found to have an increased risk of
      complications than type 1 DM. Complications of diabetes were seen in 43.7% of the
      diabetic cases. Diabetic dermopathy, loss of hair over the legs, diabetic foot
      ulcer, and so on, were found to be the cutaneous markers of DM in our group of
      cases. CONCLUSION: Dermatoses were more common in diabetics than non-diabetics.
      Cutaneous infections formed the largest group of dermatoses in DM.

PMID- 22470204
TI  - Physical and psychosocial impact of acne in adult females.
AB  - BACKGROUND: Acne, the most common problem that presents to dermatologists, can
      persist beyond teen years. Although its physical and psychosocial impact is
      studied in teen years, it is poorly understood in the Indian adult population.
      AIM: To study the physical and psychosocial impact of acne in adult females.
      SETTINGS AND DESIGN: This exploratory study was done in the university setting.
      MATERIALS AND METHODS: Eleven adult, unmarried females, between the age group of
      18 and 25 years, having (mild-to-moderate), acne, for two consecutive years, were
      interviewed using a semi-structured clinical interview of the Skindex, a quality
      of-life measure for patients with skin disease, developed by Chren et al., along
      with some open-ended questions. Both qualitative and quantitative analysis was
      done to analyze the data. RESULTS: The results indicated a higher level of
      emotional and social impairment, in terms of the feelings of physical discomfort,
      anger, and the intermingling impact of these, among the participants.
      CONCLUSIONS: Acne is a common problem among adults and appears to have a
      considerable impact on the mental health, therefore, for the treatment to be
      successful, a sympathetic approach by doctors and significant others, with the
      basic psychosomatic treatment, are necessary.

PMID- 22470205
TI  - Pigmentary nevi on face have unique patterns and implications: The concept of
      Blaschko's lines for pigmentary nevi.
AB  - BACKGROUND: Nevi are proposed to reflect the mosaicism and thus generally follow
      the different archetypal patterns of mosaicism. Blaschko's lines are the most
      common pattern of mosaicism. There have been many attempts to elucidate the
      Blaschko's lines on face from the distributional patterns of different nevi, but
      studies that evaluated exclusively pigmentary nevi are sparse. AIMS: This study
      attempted to evaluate the patterns followed by different pigmentary nevi on face
      and utilized this to elucidate the pattern of embryological pigmentation on face.
      MATERIALS AND METHODS: Spatial parameters like shape, orientation, and
      distribution patterns of different flat pigmentary nevi on face were analyzed and
      graphically drawn on human facial diagram. This was compared with existing facial
      Blaschko's lines. All cases of palpable pigmented nevi like congenital and giant
      melanocytic nevi and nevus spilus were excluded. RESULTS: A total of 68 cases of
      pigmentary nevi on face (male-39, female-29) were examined. The shape and
      distribution lines were found to have a close similarity with Blaschko's lines on
      face with distinct differences. CONCLUSIONS: The concept of facial embryonic
      pigmentary 'segment', 'unit' and existence of separate Blaschko's lines for
      facial pigmentary nevi is conceived. Some insight into the pathogenesis of
      Blaschko's lines is also proposed in this study.

PMID- 22470206
TI  - A cross-sectional study of dermatological problems among differently-abled
      children.
AB  - BACKGROUND: Differently-abled children may be particularly susceptible to skin
      disorders either as a direct consequence of their disability or due of lack
      awareness regarding personal and environmental hygiene. AIM: To study the
      prevalence of skin problems in differently-abled children. MATERIALS AND METHODS:
      A total of 122 differently-abled children in two special schools were examined
      for this study. Details regarding the disabilities were obtained from the school
      records. RESULTS: More than half (53.2%) of the children had skin problems.
      Infections and infestations, acne, and dermatitis were the common dermatoses
      encountered in the present study. CONCLUSION: Periodic skin examination is of
      vital importance for all people with disabilities to reach a proper diagnosis and
      to offer treatment. Health education for teachers and parents on maintenance of
      sound personal hygiene and a clean environment is also recommended.

PMID- 22470207
TI  - Evaluation of topical potassium hydroxide solution for treatment of plane warts.
AB  - BACKGROUND: Plane wart is a common dermatological disease that is caused by human
      papilloma virus; although the rate of spontaneous recovery is high, it usually
      takes a long time to occur. Many modalities of treatments have been used but none
      of them proved to be uniformly effective. Potassium hydroxide (KOH) solution is a
      well-known keratolytic agent with many dermatological uses. OBJECTIVE: To
      evaluate the efficacy and tolerability of topical KOH solution in the treatment
      of plane warts. MATERIALS AND METHODS: A total of 250 patients with plane warts,
      consulting the department of Dermatology and Venereology of Basra Teaching
      Hospital between March 2008 and October 2009, were enrolled in this opened
      therapeutic trial study. Patients were divided into two age and sex cross-matched
      equal groups; patients in group (A) were treated with topical 5% KOH solution
      once at night, while patients in group (B) were treated with topical 10% KOH
      solution once nightly. Only 107 patients from group (A) and 95 patients from
      group (B) completed the study, while the remainders were defaulted for unknown
      reasons. The patients were evaluated at second and fourth week to assess the cure
      rates and side effects, those patients who showed complete cure were followed up
      for 3 months to detect any recurrence. RESULTS: At the end of second week, 9.3%
      of group (A) patients showed complete disappearance of their warts, vs 66.3% of
      group (B) patients. At the end of fourth week, 80.3% of group (A) patients showed
      complete response in comparison with 82.1% of group (B) patients. The side
      effects for the treating solution in both concentrations include itching, burning
      sensation, erythema, and temporary dyspigmentations, that were reported in 77.6%
      of group (A) patients in comparison with 90.5% of group (B) patients. Recurrence
      rate was reported in 5.8% of group (A) patients vs 5.1% of group (B) patients
      during the three months period of follow-up. CONCLUSIONS: Topical KOH solution is
      proved to be an effective and safe treatment of plane warts in both
      concentrations (5% and 10%) with no important side effects.

PMID- 22470208
TI  - Reticulate acropigmentation of dohi: a case report with insight into
      genodermatoses with mottled pigmentation.
AB  - Reticulate acropigmentation of Dohi also called dyschromatosis symmetrica
      hereditaria or symmetrical dyschromatosis of the extremities is an autosomal
      dominant inherited disorder. It is characterized by mottled pigmentation with
      patchy depigmentation commonly over the back of the hands and feet and sometimes
      on the arms and legs.

PMID- 22470209
TI  - Blastic plasmacytoid dendritic cell neoplasm presenting as fever with diffuse
      cutaneous nodules.
AB  - A young man, presented with high-grade fever and disseminated asymptomatic skin
      lesions of 6-weeks duration. Cutaneous examination revealed multiple infiltrated
      monomorphic skin-colored papules and nodules upto 2*2 cm all over scalp, face,
      trunk and extremities. Light microscopy of nodules showed diffuse infiltration of
      dermis and subcutis by a tumor composed of medium to large cells with round to
      ovoid nuclei with fine chromatin, few with visible nucleoli and scanty to
      moderate amounts of eosinophilic cytoplasm. Tumor cells were positive for CD4,
      CD8, CD56 and negative for CD30, terminal deoxynucleotidyl transferase and Alk-1.
      Excised axillary lymph node showed similar morphologic and immunohistochemical
      findings. There was bone marrow involvement with infiltrate of large
      atypical/immature lymphoid cells. Diagnosis of blastic plasmacytoid dendritic
      cell neoplasm was made. This is a rare neoplasm. presenting commonly in the skin,
      with or without concurrent extracutaneous disease.

PMID- 22470210
TI  - Progressive and extensive ulcerations in a girl since 4 months of age: the
      difficulty in diagnosis of pyoderma gangrenosum.
AB  - A female child developed multiple, progressive, therapy-resistant, painful large
      ulcers, vesicles, and pustules since her 4 months of age. The ulcers were large,
      some even measured more than 8 cm; most had violaceous undermined margin with
      surrounding erythematous halo, raw and crusted surface and were distributed
      extensively over scalp, face, ear, trunk, buttocks, thigh, legs, dorsum of hands,
      and feet without any mucosal involvement. After detail clinical examination and
      investigation, it was diagnosed as a case of pyoderma gangrenosum. Extensive
      search did not reveal any systemic abnormality or detect any infective etiology.
      The case highlights the problems of diagnosis of multiple ulcers at very early
      age.

PMID- 22470211
TI  - Malignant proliferating trichilemmal tumor.
AB  - Proliferating trichilemmal tumor (PTT) is a benign tumor originating from the
      outer root sheath of a hair follicle. Malignant transformation in case of PTT is
      very rare and unusual finding. It is usually confused with squamous cell
      carcinoma both sharing many common features. So the identification of malignant
      PTT is very essential. Only 39 well-documented cases of malignant proliferating
      trichilemmal cyst have been published to date in the English language literature.
      We hereby present a case of a 75-year-old female patient with a rapidly growing
      swelling on the scalp.

PMID- 22470212
TI  - Epithelioid hemangioendothelioma: a rare vascular tumor.
AB  - Epithelioid hemangioendothelioma is an intermediate-grade vascular tumor arising
      from the vascular endothelium, which usually arises in soft tissue, and skin
      involvement is extremely rare. We report a case that presented with primary
      cutaneous tumor involving the whole limb and was present since birth.

PMID- 22470213
TI  - Unusual presentation of cutaneous leishmaniasis.
AB  - Two patients with mini-volcano type of skin lesions which showed histopathologic
      features of cutaneous leishmaniasis (CL) have been described. It was localised
      and linear in one case while widespread in the other. Both responded to sodium
      stibogluconate. The importance of recognising new emerging foci of CL is
      emphasised.

PMID- 22470214
TI  - Multisystem Langerhans cell histiocytosis in adult.
AB  - Langerhans cell histiocytosis (LCH), is a rare disorder, clinically presents with
      heterogeneous manifestations, and has an unpredictable outcome. Commonly seen in
      infancy or early childhood, the disorder is characterized by proliferation of
      abnormal and clonal Langerhans cell in skin, bone, lymph nodes, lungs, liver,
      spleen, and bone marrow. Occurrence of LCH in adults is rare. Here, we report the
      case of an adult with acute onset of polymorphic eruptions all over the body,
      which on biopsy showed features of multisystem LCH, and was confirmed by
      immunohistochemistry. Although multisystem LCH has a poor prognosis, our patient
      responded well to chemotherapy.

PMID- 22470215
TI  - Ashy dermatosis: a controversial entity.
AB  - We present here the case of a young Indian male with slowly progressive, diffuse
      darkening of the face, arms, neck, and trunk. The patient was not taking any
      medication and there was no history of any previous skin disease and the mucous
      membrane was not involved. These findings are consistent with a diagnosis for
      ashy dermatosis of unknown etiology.

PMID- 22470216
TI  - A clinicopathological study of cutaneous tuberculosis at Dibrugarh district,
      Assam.
AB  - BACKGROUND: Cutaneous tuberculosis forms a small subset of extra pulmonary
      tuberculosis and has a worldwide distribution. AIMS: The present study is an
      attempt to find out the incidence, clinical spectrum, and histopathological
      features of cutaneous tuberculosis. MATERIALS AND METHODS: A total of 42 cases of
      newly diagnosed patients of cutaneous tuberculosis attending dermatology out
      patient department over a period of 1 year were included in the study. A detailed
      clinical examination and investigations including histopathological examination
      were carried out. RESULTS: Scrofuloderma was the most common form seen in 50%
      cases followed by lupus vulgaris in 42.86%, tuberculosis verrucosa cutis in
      4.76%, and lichen scrofulosorum in 2.38% cases. The Mantoux test was positive in
      83.33% cases. Characteristic tuberculoid granulomas were seen in 72.22% cases of
      lupus vulgaris, 42.86% cases of scrofuloderma and all cases of tuberculosis
      verrucosa cutis and lichen scrofulosorum. CONCLUSION: Cutaneous tuberculosis is
      still highly prevalent in upper Assam. Early diagnosis and treatment are
      essential to prevent its complications.

PMID- 22470217
TI  - Latex allergy in clinical practice.
AB  - A continuous exposure or contact to latex products may sensitize the human body
      by causing mild to fatal reactions. Despite the availability of the literature,
      medical personnel are still unaware of the implications of the use of latex
      materials. The increased awareness to prevent the transmission of infectious
      blood borne pathogens has lead to increased usage of medical gloves among health
      care workers. This increased usage of medical gloves, along with improved methods
      in diagnosing latex allergy, has been the reason for the rise in the number of
      reported cases. This has lead to recognition of latex allergy as a serious
      medical concern. Patients in high-risk groups must be assessed carefully, so that
      appropriate protocols can be used to protect them from contact with latex.

PMID- 22470218
TI  - Pyoderma vegetans of glans penis.

PMID- 22470219
TI  - Facial demodicidosis: a diagnostic challenge.

PMID- 22470220
TI  - No hypopigmented lesion, no nerve thickening, but its leprosy!

PMID- 22470221
TI  - Familial Michelin tire baby syndrome.

PMID- 22470222
TI  - Sarcoidosis following sputum positive pulmonary tuberculosis: a rare entity.

PMID- 22470223
TI  - Propofol extravasation and tissue necrosis.

PMID- 22470224
TI  - Retraction notice.

PMID- 22470225
TI  - Nitrile-Containing Fischerindoles from the Cultured Cyanobacterium Fischerella
      sp.
AB  - Chemical investigation of the cultured cyanobacterium Fischerella sp. (SAG strain
      number 46.79) led to the isolation of four nitrile-containing indole alkaloids,
      namely 12-epi-fischerindole I nitrile (1), deschloro 12-epi-fischerindole I
      nitrile (2), 12-epi-fischerindole W nitrile (3), and deschloro 12-epi
      fischerindole W nitrile (4) along with a known metabolite hapalosin. The
      structures were determined by detailed spectroscopic analyses on the basis of 1D
      and 2D NMR and HRESIMS data. All isolates were evaluated for cytotoxicity against
      human cancer cells and for 20S proteasome inhibition. Deschloro 12-epi
      fischerindole I nitrile (2) was found to be weakly cytotoxic against HT-29 cells
      with an ED(50) value of 23 MUM. Hapalosin showed weak cytotoxicity against HT-29
      and MCF-7 cells with ED(50) values of 22 and 27 MUM, respectively, as well as
      moderate 20S proteasome inhibition with an IC(50) value of 12 MUM. Compounds 1-4
      all contain a nitrile moiety instead of the isonitrile found in all
      fischerindoles reported to date. Compounds 3 and 4 also display a new carbon
      skeleton, in which a six-membered ring replaces the five-membered ring normally
      found in fischerindole-type alkaloids.

PMID- 22470227
TI  - Fine needle aspiration cytology of ovarian tumors with histological correlation.
AB  - BACKGROUND: Till today, there has been some hesitation to accept the role of fine
      needle aspiration cytology (FNAC) in pelvic mass. We have tried to study the role
      of ultrasonography (USG) and computed tomography (CT) guided FNAC as diagnostic
      and supportive investigation for ovarian tumors. AIM: To evaluate the current
      status of image-directed percutaneous aspiration of ovarian neoplasm for the
      purpose of early detection of malignancy. MATERIALS AND METHODS: Seventy-four
      fine needle aspirations of ovarian neoplasms were performed between January 2007
      and December 2008 by transabdominal approach under USG and CT guidance and
      correlated with histopathological findings and tumor markers. RESULTS: A total of
      47 (63.5%) cases were assessed as malignant and 21 (28.3%) as benign and 6 (8.1%)
      as inconclusive. The neoplastic lesions were categorized as per World Health
      Organization (WHO) classification. CONCLUSION: With the availability of modern
      techniques, USG and CT guided FNAC can be an optimum modality for the diagnosis
      of primary and metastatic ovarian neoplasms and evaluation of recurrent malignant
      tumors, which has great impact on patient management consequently.

PMID- 22470228
TI  - Intellectual property: Business of brains!

PMID- 22470226
TI  - Alcohol-Related Problems among Sexual Minority Women.
AB  - In this article I describe the historical context for research on sexual minority
      women's drinking, including the age-old tendency to link homosexuality and
      alcoholism; I summarize gaps and limitations that characterized much of the
      research on sexual minority women's drinking over the past several decades; and I
      review recent literature to highlight progress in the field-with a particular
      focus on my own research related to risk and protective factors for heavy
      drinking and drinking-related problems among sexual minority women. I conclude
      with a discussion of barriers to treatment for sexual minority women and
      recommendations for substance abuse treatment providers.

PMID- 22470229
TI  - Management of intellectual property rights in India: An updated review.
AB  - The World Trade Organization's agreement on Trade-Related Aspects of Intellectual
      Property Rights set global minimum standards for the protection of intellectual
      property, substantially increasing and expanding intellectual property rights,
      and generated clear gains for the pharmaceutical industry and the developed
      world. The present review elaborates all aspects of Intellectual Property Rights
      in detail, along with their protection criteria.

PMID- 22470232
TI  - Therapeutics of stem cells in periodontal regeneration.
AB  - The structure and composition of the periodontium are affected in many acquired
      and heritable diseases, and the most significant among these is periodontal
      disease. Periodontal regeneration is considered to be organically promising but
      clinically capricious. The principal requirements for tissue engineering are the
      incorporation of appropriate numbers of responsive progenitor cells and the
      presence of bioactive levels of regulatory signals within an appropriate
      extracellular matrix or carrier construct. Stem cell therapy is a treatment that
      uses stem cells, or cells that come from stem cells, to replace or to repair a
      patient's cells or tissues that are damaged. And, recent progress in stem cell
      research and in tissue engineering promises novel prospects for tissue
      regeneration in dental practice in the future, with regeneration of a functional
      and living tooth as one of the most promising therapeutic strategies for the
      replacement of a diseased or damaged tooth.

PMID- 22470230
TI  - Protein kinase C modulation of thermo-sensitive transient receptor potential
      channels: Implications for pain signaling.
AB  - A variety of molecules are reported to be involved in chronic pain. This review
      outlines the specifics of protein kinase C (PKC), its isoforms and their role in
      modulating thermo-sensitive transient receptor potential (TRP) channels TRPV1-4,
      TRPM8, and TRPA1. Anatomically, PKC and thermo-sensitive TRPs are co-expressed in
      cell bodies of nociceptive dorsal root ganglion (DRG) neurons, which are used as
      physiological correlates of peripheral and central projections involved in pain
      transmission. In the past decade, modulation of painful heat-sensitive TRPV1 by
      PKC has received the most attention. Recently, PKC modulation of other newly
      discovered thermo-sensitive pain-mediating TRPs has come into focus. Such
      modulation may occur under conditions of chronic pain resulting from nerve damage
      or inflammation. Since thermo-TRPs are primary detectors of acute pain stimuli,
      their modulation by PKC can severely alter their function, resulting in chronic
      pain. Comprehensive knowledge of pain signaling involving interaction of specific
      isoforms of PKC with specific thermo-sensitive TRP channels is incomplete. Such
      information is necessary to dissect out modality specific mechanisms to better
      manage the complex polymodal nature of chronic pain. This review is an attempt to
      update the readers on current knowledge of PKC modulation of thermo-sensitive
      TRPs and highlight implications of such modulation for pain signaling.

PMID- 22470233
TI  - Immunity over inability: The spontaneous regression of cancer.
AB  - The spontaneous healing of cancer is a phenomenon that has been observed for
      hundreds and thousands of years and after having been the subject of many
      controversies, it is now accepted as an indisputable fact. A review of past
      reports demonstrates that regression is usually associated with acute infections,
      fever, and immunostimulation. It is stated that in 1891, William Coley of New
      York's Memorial Hospital developed the most effective single-agent anticancer
      therapy from nature, which faded into oblivion for various reasons. Cancer
      therapies have been standardized and have improved since Coley's day, but
      surprisingly modern cancer patients do not fare better than patients treated 50
      or more years ago as concluded by researchers in 1999. This article peeks into
      the history of immunostimulation and the role of innate immunity in inducing a
      cure even in advanced stages of malignancy. The value of Coley's observation is
      that rather than surviving additional years with cancer, many of the patients who
      received his therapy lived the rest of their lives without cancer. In our
      relentless efforts to go beyond nature to fight cancer, we often overlook the
      facts nature provides to heal our maladies.

PMID- 22470231
TI  - Regulation of adult neurogenesis in the hippocampus by stress, acetylcholine and
      dopamine.
AB  - Neurogenesis is well-established to occur during adulthood in two regions of the
      brain, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the
      dentate gyrus in the hippocampus. Research for more than two decades has
      implicated a role for adult neurogenesis in several brain functions including
      learning and effects of antidepressants and antipsychotics. Clear understanding
      of the players involved in the regulation of adult neurogenesis is emerging. We
      review evidence for the role of stress, dopamine (DA) and acetylcholine (ACh) as
      regulators of neurogenesis in the SGZ. Largely, stress decreases neurogenesis,
      while the effects of ACh and DA depend on the type of receptors mediating their
      action. Increasingly, the new neurons formed in adulthood are potentially linked
      to crucial brain processes such as learning and memory. In brain disorders like
      Alzheimer and Parkinson disease, stress-induced cognitive dysfunction, depression
      and age-associated dementia, the necessity to restore brain functions is
      enormous. Activation of the resident stem cells in the adult brain to treat
      neuropsychiatric disorders has immense potential and understanding the mechanisms
      of regulation of adult neurogenesis by endogenous and exogenous factors holds the
      key to develop therapeutic strategies for the debilitating neurological and
      psychiatric disorders.

PMID- 22470234
TI  - Periodontitis: A risk for delivery of premature labor and low birth weight
      infants.
AB  - Periodontitis is a destructive inflammatory disease of the supporting tissues of
      the teeth and is caused by specific microorganisms or a group of specific
      microorganisms. Association of periodontal infection with organ systems like
      cardiovascular system, endocrine system, reproductive system, and respiratory
      system makes periodontal infection a complex multiphase disease. Inflamed
      periodontal tissues produce significant amounts of pro-inflammatory cytokines,
      mainly interleukin 1 beta (IL-1beta), IL-6, prostaglandin E2 (PGE2), and tumor
      necrosis factor alpha (TNF-alpha), which may have systemic effects on the host.
      Low birth weight, defined as birth weight less than 2500 g, continues to be a
      significant public health issue in both developed and developing countries.
      Research suggests that the bacteria that cause inflammation in the gums can
      actually get into the bloodstream and target the fetus, potentially leading to
      premature labor and low birth weight (PLBW) babies. One reasonable mechanism for
      this is the deleterious effect of endotoxin released from gram-negative bacteria
      responsible for periodontal disease. Hence, periodontal disease appears to be an
      independent risk factor for PLBW and there is a need to expand preventive
      measures for pregnant women in coordination with the gynecological and dental
      professions.

PMID- 22470236
TI  - Maytenus heterophylla and Maytenus senegalensis, two traditional herbal
      medicines.
AB  - Maytenus heterophylla (Eckl. and Zeyh.) N.K.B. Robson and Maytenus senegalensis
      (Lam.) Exell are two African shrubs or trees that go under the common name of
      spike thorn, which belong to the Celastraceae family. Different plant parts of
      this species are largely used in traditional medicine for infectious and
      inflammatory diseases treatment. Several studies have been reported for both
      these species, but there are no recent review articles focusing microscopic,
      phytochemistry and pharmacological studies. The aim of this review is to
      summarize the information about these two African traditional medicines. Such
      kind of data can be applied in future experimental work and may guide future
      studies, namely in the field of validation of traditional medicine.

PMID- 22470235
TI  - Science behind human saliva.
AB  - Saliva is a complex fluid, which influences oral health through specific and
      nonspecific physical and chemical properties. The importance of saliva in our
      everyday activities and the medicinal properties it possesses are often taken for
      granted. However, when disruptions in the quality or quantity of saliva do occur
      in an individual, it is likely that he or she will experience detrimental effects
      on oral and systemic health. Often head and neck radiotherapy has serious and
      detrimental side effects on the oral cavity including the loss of salivary gland
      function and a persistent complaint of a dry mouth (xerostomia). Thus, saliva has
      a myriad of beneficial functions that are essential to our well-being. Although
      saliva has been extensively investigated as a medium, few laboratories have
      studied saliva in the context of its role in maintaining oral and general health.

PMID- 22470237
TI  - Ozone therapy: A clinical review.
AB  - Ozone (O(3)) gas discovered in the mid-nineteenth century is a molecule
      consisting of three atoms of oxygen in a dynamically unstable structure due to
      the presence of mesomeric states. Although O(3) has dangerous effects, yet
      researchers believe it has many therapeutic effects. Ozone therapy has been
      utilized and heavily studied for more than a century. Its effects are proven,
      consistent, safe and with minimal and preventable side effects. Medical O(3) is
      used to disinfect and treat disease. Mechanism of actions is by inactivation of
      bacteria, viruses, fungi, yeast and protozoa, stimulation of oxygen metabolism,
      activation of the immune system. Medication forms in a gaseous state are somewhat
      unusual, and it is for this reason that special application techniques have had
      to be developed for the safe use of O(3). In local applications as in the
      treatment of external wounds, its application in the form of a transcutaneous
      O(3) gas bath has established itself as being the most practical and useful
      method, for example at low (sub-atmospheric) pressure in a closed system
      guaranteeing no escape of O(3) into the surrounding air. Ozonized water, whose
      use is particularly known in dental medicine, is optimally applied as a spray or
      compress. Diseases treated are infected wounds, circulatory disorders, geriatric
      conditions, macular degeneration, viral diseases, rheumatism/arthritis, cancer,
      SARS and AIDS.

PMID- 22470238
TI  - Biofilm: A dental microbial infection.
AB  - Recent advances in research technology have allowed researchers to study bacteria
      in their natural environment. Dental biofilm forms via an ordered sequence of
      events, resulting in structured and functionally organized species rich microbial
      community and modern molecular biological techniques have identified about 1000
      different bacterial species in the dental biofilm, twice as many as can be
      cultured. Sites for biofilm formation include all kinds of surfaces: natural
      materials above and below ground, metals, plastics, medical implant materials
      even plant and body tissue. Wherever you find a combination of moisture,
      nutrients and a surface, you are likely to find biofilm. The biofilm is used to
      describe the communities of micro-organisms attached to a surface; such microbes
      are usually spatially organized into three-dimension structure and are enclosed
      in matrix of extracellular material derived both from the cells themselves and
      from the environment. Dental biofilm pathogenicity in the oral cavity is
      magnified by specific biofilm characteristics and modern molecular biological
      techniques have identified about 1000 different bacterial species in the dental
      biofilm, twice as many as can be cultured. Adaptation to a biofilm lifestyle
      involves regulation of a vast set of genes, and the micro-organisms are thus able
      to optimize phenotypic properties for the particular environment.

PMID- 22470239
TI  - Phytochemical investigation and evaluation of antinociceptive activity of
      ethanolic extract of Dalbergia sissoo (Roxb.) bark.
AB  - The antinociceptive activity of ethanolic extract of the plant bark of Dalbergia
      sissoo (Roxb.) was investigated using tail flick method on Wistar rats. Three
      different dose levels (300, 500, and 1000 mg/kg) in 0.5% carboxyl methyl
      cellulose (CMC) were administered by p.o. route. The antinociceptive activities
      of the all doses were compared with that of the standard drug asprin (300 mg/kg)
      administered by p.o. route and the results were found to be significant (P <
      0.01). At the above doses, the extract exhibited significant and dose-dependent
      antinociceptive activity. Phytochemical investigation of the ethanolic extract
      indicated the presence of carbohydrates, proteins, amino acids, phenolic
      compounds, and flavanoids. The antinociceptive activity of the bark extract of D.
      sissoo may be due to the presence of phytochemical constituents such as
      flavanoids. The acute toxicity study revealed that ethanolic extract was not
      toxic up to 3000 mg/kg body weight.

PMID- 22470240
TI  - The effect of nitric oxide inhibitors and Snitroso-Nacetylpenicillamine on
      glucose concentration in an animal model.
AB  - BACKGROUND: Nitric oxide (NO) is becoming an increasingly important signaling
      molecule implicated in a growing number of physiological and pathophysiological
      processes. Research on the effect of NO donors on glucose metabolism in
      peripheral tissues have grown rapidly in the last decade. This study examined the
      effects of N(G)methyl-L-arginine acetate (L-NMMA) and N(G)methyl-L-arginine ester
      (L-NAME) on fasting and postprandial blood glucose concentrations. The study also
      investigated if L-NMMA and L-NAME decrease the hyperglycemic effect caused by the
      NO donor S-nitrosoN-acetylpenicillamine (SNAP) in normoglycemic rats. RESULTS: L
      NAME and L-NMMA significantly lowered the postprandial blood glucose
      concentrations. Mean postprandial blood glucose concentrations in rats treated
      with L-NAME were 5.04 +/- 0.07 mmol/L at 120 min, 4.62 +/- 0.19 mmol/L at 150 min
      and 4.36 +/- 0.17 mmol/L at 180 min time points compared with 5.46 +/- 0.14 (P =
      0.029), 5.20 +/- 0.17 mmol/L (P = 0.036), and 4.89 +/- 0.14 mmol/L (P = 0.015) at
      the same time points respectively for saline control. Mean blood glucose
      concentrations in rats treated with L-NMMA were 4.35 +/- 0.23 mmol/L (P = 0.0018)
      at 120 min, 4.60 +/- 0.14 mmol/L (P = 0.090) at 150 min and 3.88 +/- 0.16 mmol/L
      (P 0.001) at 180 min. There were significant differences in mean postprandial
      blood glucose concentrations in rats treated with SNAP, compared with those
      treated with L-NAME and SNAP at 90 min (P = 0.012), 180 min (P = 0.013) and 210
      min (P < 0.0001). In addition, there were significant differences in mean
      postprandial blood glucose concentrations in rats treated with SNAP compared with
      those treated with L-NMMA and SNAP at 90 min (P = 0.0011), 180 min (P = 0.015)
      and 210 min (P = 0.0077). CONCLUSION: The nitric oxide synthase [NOS] inhibitors
      were effective in reducing postprandial blood glucose concentration in rats
      treated with SNAP. This suggests that although SNAP is an effective
      antihypertensive agent it decreases glucose tolerance which can be improved by
      the use of NOS inhibitors such as L-NMMA or L-NAME. These drugs could be
      beneficial in controlling blood glucose tolerance in rats administered with SNAP,
      and possibly in humans.

PMID- 22470241
TI  - A scientometric analysis of Indian research output in medicine during 1999-2008.
AB  - OBJECTIVE: This study analyzes the research activities of India in medicine
      during 1999-2008, based on the total publication output, its growth rate, quality
      of papers published and rank of India in the global context. Patterns of
      international collaborative research output and the major partner countries of
      India are also discussed. This study also evaluates the research performance of
      different types of Indian medical colleges, hospitals, research institutes,
      universities and research foundations and the characteristics of published
      literature in Indian and foreign journals. It also analyzes the medical research
      output by disease and organs. MATERIALS AND METHODS: The publication data on
      medicine has been retrieved by using SCOPUS database. RESULTS: India holds 12th
      rank among the productive countries in medicine research consisting of 65,745
      papers with a global publication share of 1.59% and registering a growth rate of
      76.68% for the papers published during 1999-2003 to 2004-2008. CONCLUSION: High
      quality research in India is grossly inadequate and requires strategic planning,
      investment and resource support. There is also a need to improve the existing
      medical education system, which should foster research culture.

PMID- 22470242
TI  - Obesity in Kolkata children: Magnitude in relationship to hypertension.
AB  - BACKGROUND: Limited data is available from India regarding the distribution and
      profile of childhood obesity and hypertension. MATERIALS AND METHODS: A
      population based cross-sectional study was conducted in the urban schools of
      Kolkata. Using stratified random sampling method, 979 participants were selected.
      Body mass index (BMI) status and blood pressure (BP) were estimated using
      standard protocol and their various correlates regarding sociodemographic
      characteristics were looked into. RESULTS: Majority (38.92%) of the study
      population were in the preadolescent group followed by adolescent group (33.40%).
      Male constituted 52.09%, overweight was more prevalent among preadolescent age
      group (22.57%). Overall 27 cases of prehypertension were found of which 19
      (70.37%, n=27) were in the adolescent age group. There was no significant
      association between ages with increased BMI status. We detected total 15 cases
      (1.53%) of hypertension in our study population and three-fourths of them were
      from adolescent age group. However, significant association was seen between high
      BP with increasing age. Average fast food intakes and screen time was higher in
      obese as compared to their normal peers. Upper and upper-middle social status
      contributed to higher number of obese/overweight and hypertensive children and
      was the significant risk factor. CONCLUSION: Childhood obesity and hypertension
      were found to be common in the city of Kolkata which suggest the need for greater
      public awareness programs on these morbidities.

PMID- 22470243
TI  - Serum malondialdehyde level: Surrogate stress marker in the Sikkimese diabetics.
AB  - BACKGROUND: The pbreakdown of phospholipids lead to accumulation of
      malondialdehyde (MDA) that is preferred as a surrogate marker of oxidative stress
      in diabetics. OBJECTIVE: To compare serum MDA levels along with other biochemical
      parameters between type 2 diabetic patients with and without complications.
      MATERIALS AND METHODS: This cross-sectional study was carried out in the
      Department of Biochemistry of a tertiary care teaching hospital in Sikkim on 60
      type 2 diabetics and compared with 100 non-diabetic participants. The un
      hemolyzed blood samples were used for estimation of biochemical parameters; MDA
      was estimated in serum by using trichloroacetic acid (TCA) and 1% thiobarbituric
      acid (TBA). Whole blood was used for estimation of glycated hemoglobin. The
      comparison of different parameters between cases and control was calculated by
      using Student's t test. RESULTS: In the study and control groups, no significant
      difference was noted with regard to independent variables. The fasting and
      postprandial serum glucose along with glycated hemoglobin from whole blood and
      the lipid profile differed significantly between the study and control groups.
      Overall, tmean serum MDA level in the study group was significantly higher thanin
      the controls. Male sex, addiction to tobacco (smoking and smokeless inclusive),
      longer duration of diabetes (>=5 years), and presence of complications (both
      microvascular and macrovascular) significantly increased the MDA level.
      CONCLUSION: To sum up, the serum MDA level was observed to be significantly high
      in diabetics with and without complication along with other parameters.

PMID- 22470244
TI  - Fine needle aspiration cytology as the primary diagnostic tool in thyroid
      enlargement.
AB  - BACKGROUND: In the preoperative decision-making of the thyroid swellings, fine
      needle aspiration cytology (FNAC) is becoming an ever more vital tool.
      OBJECTIVES: To compare the advantage of preoperative FNAC of thyroid swellings
      with postoperative histopathology to reach a consensus protocol as a simple
      procedure for diagnosis and optimal management of thyroid swellings. MATERIALS
      AND METHODS: A prospective study of preoperative FNAC was carried out on 178
      incidental thyroid swellings attending a tertiary care centre in Kishanganj,
      Bihar. Evidence-based surgical interventions were done, irrespective of FNAC
      findings and diagnosis was confirmed by histopathological examination (HPE)
      postoperatively in all the cases. RESULTS: In the FNAC, preponderance of the
      cases (75.84%) was colloid goitre followed by granulomatous thyroiditis;
      follicular carcinoma was noted in 7.30 percent and anaplastic carcinoma in 3.37
      percent of cases. Histopathological examination showed colloid goitre
      predominantly (76.97%), followed by follicular carcinoma (8.99%). The overall
      prevalence of malignancy was 11.24 percent diagnosed by HPE and 9.55 percent by
      FNAC. In our FNAC series sensitivity of was 90 percent while specificity was 100
      percent; accuracy was 98.88 percent. Predictive value of a positive test and
      negative tests was 100 percent and 98.75 percent respectively. CONCLUSION: The
      study highlights that FNAC should be treated as a first-line diagnostic test for
      thyroid swellings to guide the management though this is not a substitute for HPE
      as a need to improve primary healthcare in India.

PMID- 22470245
TI  - Evaluation of Ondansetron-induced QT interval prolongation in the prophylaxis of
      postoperative emesis.
AB  - BACKGROUND: To avert nausea and vomiting the 5-Hydroxytryptamine3 (5-HT3)
      antagonists have become the first line of treatment ifassociated with
      cardiovascular effects andappear to cause QT prolongation. OBJECTIVE: Evaluate
      the effect of 1 mg, 4 mg, and 8 mg bolus doses of intravenous Ondansetron,
      relative to placebo, in prevention of postoperative nausea and vomiting (PONV)
      and to find out the changes of QT interval corrected for heart rate (QTc).
      MATERIALS AND METHODS: This prospective randomized, placebo-controlled, double
      blind study was carried out among 136 adult participants of both sexes in a
      tertiary care postgraduate teaching institute at Kolkata. mg, 4 mg or 8 mg inj.
      Ondansetron was diluted to 10 ml with normal saline, was infused 30 min before
      extubation in relation with a control group. Time to first rescue antiemetic
      medication and in QTc interval at different time intervals, in each group was
      noted in different in the various surgical operation theaters (OTs). RESULTS:
      Requirement of the first rescue antiemetic in the postoperative period between 60
      to 120 min in the mg, 4 mg or 8 mg Ondansetron groups was in 28%, 24% and 7%
      participants respectively; between 120 to 240 min in 63%, 72% and 57%
      respectively; and within 360 min in 9%, 4% and 36% respectively. Significant and
      maximal QTc prolongation was observed in the participants with mg or 8 mg
      Ondansetron 3 and 5 min of drug administration. CONCLUSIONS: One mg Ondansetron
      in healthy adult participants can effectively prevent PONV causing no or
      insignificant prolongation of QTc interval.

PMID- 22470246
TI  - Heterotopic salivary gland tissue: A report of two cases.
AB  - The heterotopic salivary gland or salivary choristoma is defined as a tumor -
      like growth of otherwise normal salivary gland found in an abnormal location. In
      general, salivary gland tissue is not observed in the gingiva, with only isolated
      case reports having been found. The occurrence of the case in the midline,
      especially in the anterior two - thirds of the hard palate, has not been
      documented so far (PubMed search engine). It is apparent that these reported
      cases constitute a unique clinico -pathologic entity. Clinically, they appear as
      soft tissue tumors and are composed of lobules of salivary gland tissue.

PMID- 22470248
TI  - From The Editor's Desk.

PMID- 22470247
TI  - Klestadt's cyst.
AB  - The nasolabial cyst is a rare nonodontogenic cyst originating in maxillofacial
      soft tissues. In the previous reports and literature, it is mentioned that
      nasolabial cyst clinical features of an asymptomatic swelling beneath the ala of
      nose and characteristic lip swelling are diagnostic. This is a case report of a
      36-year-old male, who reported to our department with the chief complaint of
      swelling lateral to right ala of nose since 4 months. Characteristic lip swelling
      was missing. The reason for this unusual finding is not documented in the
      literature.

PMID- 22470249
TI  - Another perfect storm.

PMID- 22470250
TI  - The five ps of acute ischemic stroke treatment: parenchyma, pipes, perfusion,
      penumbra, and prevention of complications.
AB  - Stroke is a treatable disease. Despite the therapeutic nihilism of the past, the
      advent of thrombolysis has changed the way stroke treatment is approached. Acute
      ischemic stroke is a challenging and heterogeneous disease, and treatment must be
      based on an understanding of the underlying pathophysiology of ischemia.
      Interventions are designed to improve neuronal salvage and outcome. The
      underlying tenets of stroke therapy focus on the brain parenchyma, arterial flow
      (pipes), perfusion, the ischemic milieu or penumbra, and prevention of
      complications. This article focuses on the practical issues of ischemic stroke
      care with a brief review of supporting literature.

PMID- 22470251
TI  - Multifactorial approach to the primary and secondary prevention of
      atherosclerosis.
AB  - We review data regarding the importance of various conventional and evolving
      atherosclerosis risk factors. In addition, we discuss a multifactorial approach
      to the primary and secondary prevention of major vascular events, including
      stroke.

PMID- 22470252
TI  - Influence of preoperative risk factors on outcome after carotid endarterectomy.
AB  - As supported by level 1 multicenter randomized trial data, carotid endarterectomy
      (CEA) has a very low risk of perioperative morbidity and excellent durability,
      and provides significant long-term reductions of the risk of stroke. At Ochsner,
      our 1.1% risk of major stroke or death after CEA (n=366) is a demonstration of
      the safety of this procedure in experienced hands. This treatment modality
      continues to be the gold standard for most patients with carotid artery occlusive
      disease. Almost half of these patients treated with CEA were considered "high
      risk" as defined by ineligibility for past or present randomized carotid trials.
      Importantly, these "high-risk" patients had outcomes that were not statistically
      different from "low-risk" trial-eligible patients. Thus, evidence-based decision
      making does not support the routine use of investigational carotid stenting in
      "high-risk" trial-ineligible patients. However, carotid stenting is clearly a
      valuable alternative for selected patients. Our challenge is to precisely define
      which patients will most benefit from medical, surgical, or catheter-based
      therapy for carotid artery occlusive disease.

PMID- 22470253
TI  - Extracranial-intracranial bypass in cerebral ischemia.
AB  - While the utility of extracranial-intracranial (EC-IC) bypass versus medical
      therapy for typical stroke indications was cast in doubt in the mid-1980s, EC-IC
      bypass has continued to be useful for maintaining cerebral circulation in
      specific cases. A case report demonstrates the utility of EC-IC bypass using PET
      and SPECT scanning technologies to assess cerebral hemodynamics. While further
      studies will better define the patient population, there is a subset of stroke
      patients that benefit from cerebral revascularization.

PMID- 22470254
TI  - Vertebral and intracranial artery angioplasty.
AB  - Cerebral ischemia is due to either embolic or cerebrovascular occlusive disease,
      which most commonly occurs as a manifestation of atherosclerosis. Although
      carotid endarterectomy has been proven more effective than medical therapy in the
      treatment of cervical carotid disease, there are no effective surgical strategies
      for the management of vertebral artery or intracranial carotid disease.
      Management of patients with these conditions is well suited to a
      multidisciplinary team with the combined skills to provide optimal care.
      Percutaneous revascularization techniques with balloon angioplasty and stenting
      can be used to successfully treat occlusive disease of the vertebral and
      intracranial arteries. Percutaneous revascularization of intracranial and
      vertebral vessels with angioplasty and stenting is an effective strategy. The
      outcomes in this difficult to manage cohort of patients appears to be markedly
      improved over the natural history of this disease with medical therapy alone.

PMID- 22470255
TI  - Vascular dementia.
AB  - Many cases of age-related cognitive dementia are caused by cerebrovascular
      lesions, and various vascular syndromes can lead to cognitive impairment and
      dementia. Repeated cortical infarcts due to embolic disease of the heart or major
      cerebral vessels can cause progressive deterioration towards dementia and
      incapacitation. In classic multi-infarct dementia, cognitive deterioration is
      stepwise rather than smoothly progressive. While diagnostic technologies have
      vastly improved and added to general knowledge of the pathology of
      cerebrovascular disease, MRI, PET, and transcranial Doppler scans have
      demonstrated that significant white matter change is possible without clinically
      recognized TIA or completed stroke. In addition, patients may have initial
      complaints that are not serious enough to produce changes on mental status
      examination. Many patients have mixed dementia, exhibiting aspects of both
      degenerative brain disease and clinical evidence of strokes or significant
      changes on MRI scan. The overlap between vascular and degenerative disease is
      significant, yet the exact interaction of the pathophysiology of the vascular
      lesions and the degenerative changes is not known. The treatment of vascular or
      mixed dementia involves control of the risk factors for continued vascular events
      and treatment with the cholinesterase inhibitors.

PMID- 22470257
TI  - Francis Earnest ("Duke") LeJeune, MD.

PMID- 22470256
TI  - Brain attack.

PMID- 22470258
TI  - Scanning the literature.

PMID- 22470259
TI  - About ochsner.

PMID- 22470262
TI  - Ongoing clinical protocols at ochsner.

PMID- 22470263
TI  - Transfacial approaches to the skull base: the early contributions of harvey
      cushing.
AB  - In this report, we review Dr. Cushing's early surgical cases at the Johns Hopkins
      Hospital, revealing details of his early use of craniofacial approaches for
      malignant pathology of the skull base. Following Institutional Review Board
      approval, and through the courtesy of the Alan Mason Chesney Archives, we
      reviewed the Johns Hopkins Hospital surgical files from 1896 to 1912, which
      included three patients who underwent surgical treatment of lesions involving the
      skull base through craniofacial approaches: two adults and one child (range 3 to
      43 years). The main outcome measures were length of stay and condition recorded
      at the time of discharge. The indications for surgery included osteochondroma of
      the sphenoid sinus, sarcoma of the maxillary sinus and middle fossa, and osteoma
      of the frontal sinus. The mean length of stay was 24.5 days (range 7 to 45 days).
      Cushing employed craniofacial approaches for malignant pathology nearly 40 years
      before such techniques became widely used. He practiced the fundamentals of skull
      base surgery, including preferential removal of bone to achieving adequate
      exposure for resection. In addition, Cushing clearly understood the importance of
      proximal vascular control in approaching lesions with complex vascular
      involvement.

PMID- 22470264
TI  - Perioperative outcomes in patients undergoing the transglabellar/subcranial
      approach to the anterior skull base.
AB  - We analyzed the effect of predefined patient demographic, disease, and
      perioperative variables on the rate of complications in the perioperative period
      following subcranial surgery for anterior skull base lesion. A secondary goal of
      this study was to provide a benchmark rate of perioperative mortality and
      morbidity through comprehensive analysis of complications. Retrospective review
      of a consecutive series of patients (n = 164) who underwent the
      transglabellar/subcranial approach to lesions of the anterior skull base between
      December 1995 and November 2009 in a tertiary referral center. Main outcome
      measures were perioperative morbidity and mortality. No perioperative mortalities
      were observed over the period of consecutive review. The overall complication
      rate was 28.7%, with 30 (18%) patients experiencing major complication.
      Multivariate analysis revealed that the following variables were independent
      predictors of perioperative complication of any type: positive margins on final
      pathology, perioperative lumbar drain placement, and dural invasion. The
      subcranial approach provides excellent access to the anterior skull base with
      zero mortality and acceptable morbidity in comparison with other contemporary
      open surgical approaches. It should be considered a procedure with distinct
      advantages in terms of perioperative morbidity and mortality when selecting a
      therapeutic approach for patients with anterior skull base lesions.

PMID- 22470265
TI  - Transsphenoidal resection of sellar tumors using high-field intraoperative
      magnetic resonance imaging.
AB  - There has been increasing experience in the utilization of intraoperative
      magnetic resonance imaging (iMRI) for intracranial surgery. Despite this trend,
      only a few U.S centers have examined the use of this technology for
      transsphenoidal resection of tumors of the sella. We present the largest series
      in North America examining the role of iMRI for pituitary adenoma resection. We
      retrospectively reviewed our institutional experience of 59-patients who
      underwent transsphenoidal procedures for sellar and suprasellar tumors with iMRI
      guidance. Of these, 52 patients had a histological diagnosis of pituitary
      adenoma. The technical results of this subgroup were examined. A 1.5-T iMRI was
      integrated with the BrainLAB (Feldkirchen, Germany) neuronavigation system. The
      majority (94%) of tumors in our series were macroadenomas. Seventeen percent of
      tumors were confined to the sella, 49% had suprasellar extensions without
      involvement of the cavernous sinus, 34% had frank cavernous sinus invasion. All
      patients underwent at least one iMRI, and 19% required one or more additional
      sets of intraoperative imaging. In 58% of patients, iMRI led to the surgeon
      attempting more resection. A gross total resection was obtained in 67% of the
      patients with planned total resections. There was one case of permanent
      postoperative diabetes insipidus and no other instances of new hormone
      replacement. In summary, iMRI was most useful for tumors of the sella with and
      without suprasellar extension where the information from the iMRI extended the
      complete resection rate from 40 to 72% and 55 to 88%, respectively. As one would
      expect, it did not substantially increase the rate of resection of tumors with
      cavernous sinus invasion. Overall, iMRI was particularly useful in guiding
      resection safely, aiding in clinical decision making, and allowing identification
      and preservation of the pituitary stalk and normal pituitary gland. Limitations
      of the iMRI include a need for additional personnel and training as well as
      additional operative time, which diminishes over time as personnel learn to
      optimize workflow efficiency. Additional costs are mitigated in part by using the
      iMRI as an immediate postoperative scan. Other data emerging from our experience
      suggest that preservation of normal gland and thus avoidance of hypopituitarism
      may be improved by iMRI use, but longer follow-up periods are required to test
      this conclusion. iMRI can detect unsuspected complications sooner than routine
      postoperative imaging, potentially leading to improved outcomes. However, larger
      studies are needed.

PMID- 22470266
TI  - Treatment strategies for complex intracranial aneurysms: review of a 12-year
      experience at the university of cincinnati.
AB  - Complex intracranial aneurysms (CIAs) include those classified as giant, those
      located in brain regions of technically difficult access, or that involve
      arterial trunks/branches, and/or have complicated wall structure. We reviewed
      retrospectively our management of such lesions in a 12-year period. From 1997 to
      2009, 192 patients were admitted with CIAs (133 females, 59 males; average age 55
      years); 128 presented with subarachnoid hemorrhage (SAH) and 64 with unruptured,
      symptomatic CIAs. The SAH group had 73 anterior- and 55 posterior-circulation
      aneurysms. Most frequent location was middle cerebral artery. Treatment
      strategies included clipping (65.6%), coiling/stenting (28.1%), bypass (3.1%), no
      treatment (3.1%). Coiling/stenting was exclusively used for posterior-circulation
      aneurysms. Outcomes were good (modified Rankin Scale [mRS] 0 to 2) in 54 patients
      (42.2%), fair (mRS = 3 to 4) in 38 (29.7%), and poor (mRS = 5 to 6) in 36
      (28.1%). Among unruptured CIAs, there were 47 anterior- and 17 posterior
      circulation aneurysms. Most frequent location was ophthalmic. Thirty (46.9%) were
      clipped, 19 (29.7%) coiled, 6 (9.4%) by-passed, 2 (3.1%) wrapped, and 7 (10.9%)
      had no treatment. Outcomes were good in 57 patients (89%) and fair in 7 (11%).
      Good outcomes were obtained in unruptured CIAs using a multidisciplinary
      approach. Ruptured CIAs carry a significantly worse prognosis than overall SAH
      patients.

PMID- 22470267
TI  - Craniofacial Resection for Sinonasal Malignant Tumors: Statistical Analysis of
      Surgical Outcome over 17 Years at a Single Institution.
AB  - We present a retrospective analysis of surgical outcome of sinonasal malignant
      tumors. Overall survival (OS), disease-specific survival (DSS), local control
      (LC), and disease-free survival (DFS) were calculated in 32 patients. Prognostic
      factors for survival and functional outcomes were investigated. The median follow
      up period was 70 months. At 5 years, OS, DSS, LC, and DFS rates were 0.722,
      0.745, 0.851, and 0.707, respectively. Prognostic factors for poor OS were
      involvement of the frontal sinus (p = 0.023), T classification (T4, p = 0.025),
      surgical complications (p = 0.029), chemotherapy (p = 0.035) postsurgical
      infection (p = 0.043), involvement of the orbit (p = 0.048), histology (squamous
      cell carcinoma, p = 0.049), and radiotherapy (p = 0.043). Prognostic factors for
      poor DSS were radiotherapy (p = 0.030), chemotherapy (p = 0.036), positive
      surgical margin (p = 0.034), and T classification (T4, p = 0.050). LC was
      adversely influenced by surgical procedure (combined frontotemporal resection, p
      = 0.035) and positive surgical margin (p = 0.049). DFS was adversely influenced
      by positive surgical margin (p = 0.001). Prognostic factors for poor functional
      outcome were postsurgical infection (p = 0.039), postsurgical complications (p =
      0.040), tumor location (maxillary sinus, p = 0.042, orbit, p = 0.0002), number of
      sinuses involved (number of sinuses involved was inversely proportional to
      functional outcome, p = 0.027), T classification (T4 p = 0.007), pathology
      (squamous cell carcinoma, p = 0.023), and chemotherapy (p = 0.048). Craniofacial
      resection was an effective surgical option.

PMID- 22470268
TI  - Do concomitant cranium and axis injuries predict worse outcome? A trauma database
      quantitative analysis.
AB  - We performed a trauma database analysis to identify the effect of concomitant
      cranial injuries on outcome in patients with fractures of the axis. We identified
      patients with axis fractures over a 14-year period. A binary outcome measure was
      used. Univariate and multiple logistic regression analysis were performed. There
      were 259 cases with axis fractures. Closed head injury was noted in 57% and skull
      base trauma in 14%. Death occurred in 17 cases (6%). Seventy-two percent had good
      outcome. Presence of abnormal computed tomography head findings, skull base
      fractures, and visceral injury was significantly associated with poor outcome.
      Skull base injury in association with fractures of the axis is a significant
      independent predictor of worse outcomes, irrespective of the severity of the head
      injury. We propose that presence of concomitant cranial and upper vertebral
      injuries require careful evaluation in view of the associated poor prognosis.

PMID- 22470269
TI  - Morbidity profile and functional outcome of modified facial translocation
      approaches for skull base tumors.
AB  - The primary objective of this study was to evaluate morbidity associated with
      facial translocation approaches for skull base and results of various technical
      modifications. Forty consecutive patients who underwent facial translocation
      approaches for accessing skull base tumors from July 2005 to June 2010 were
      included in this study. There were 25 patients who underwent standard facial
      translocation, 4 patients medial mini, and 11 patients underwent extended facial
      translocation. Thirteen patients had benign disease and 27 patients had malignant
      disease. Resection was R0 in 36 and R1 in 4 patients. Most patients had
      acceptable cosmetic results. None of the patients had problems related to
      occlusion or speech and swallowing. The commonest complication observed was nasal
      crusting in 16 patients. Grade 2 trismus and exposure of mini plate was seen in
      three patients. Two patients developed necrosis of translocated bone. Three
      patients developed palatal fistula before modification of palatal incision.
      Facial translocation provides a satisfactory access for adequate clearance of
      skull base tumors with satisfactory aesthetic and functional results. With
      modifications of the surgical technique and implementation of new surgical tools,
      the morbidity of facial translocation approaches will continue to decrease.

PMID- 22470270
TI  - Comparison of Intraoperative Portable CT Scanners in Skull Base and Endoscopic
      Sinus Surgery: Single Center Case Series.
AB  - Precise and safe management of complex skull base lesions can be enhanced by
      intraoperative computed tomography (CT) scanning. Surgery in these areas requires
      real-time feedback of anatomic landmarks. Several portable CT scanners are
      currently available. We present a comparison of our clinical experience with
      three portable scanners in skull base and craniofacial surgery. We present
      clinical case series and the participants were from the Northwestern Memorial
      Hospital. Three scanners are studied: one conventional multidetector CT (MDCT),
      two digital flat panel cone-beam CT (CBCT) devices. Technical considerations,
      ease of use, image characteristics, and integration with image guidance are
      presented for each device. All three scanners provide good quality images.
      Intraoperative scanning can be used to update the image guidance system in real
      time. The conventional MDCT is unique in its ability to resolve soft tissue. The
      flat panel CBCT scanners generally emit lower levels of radiation and have less
      metal artifact effect. In this series, intraoperative CT scanning was technically
      feasible and deemed useful in surgical decision-making in 75% of patients.
      Intraoperative portable CT scanning has significant utility in complex skull base
      surgery. This technology informs the surgeon of the precise extent of dissection
      and updates intraoperative stereotactic navigation.

PMID- 22470271
TI  - Harvey Cushing's Approaches to Tumors in His Early Career: From the Skull Base to
      the Cranial Vault.
AB  - In this report, we review Dr. Cushing's early surgical cases at the Johns Hopkins
      Hospital, revealing details of his early operative approaches to tumors of the
      skull base and cranial vault. Following Institutional Review Board approval, and
      through the courtesy of the Alan Mason Chesney Archives, we reviewed the Johns
      Hopkins Hospital surgical files from 1896 to 1912. Participants included four
      adult patients and one child who underwent surgical resection of bony tumors of
      the skull base and the cranial vault. The main outcome measures were operative
      approach and condition recorded at the time of discharge. The indications for
      surgery included unspecified malignant tumor of the basal meninges and temporal
      bone, basal cell carcinoma, osteoma of the posterior skull base, and osteomas of
      the frontal and parietofrontal cranial vault. While Cushing's experience with
      selected skull base pathology has been previously reported, the breadth of his
      contributions to operative approaches to the skull base has been neglected.

PMID- 22470272
TI  - On "clivus chordoma: is it enough to image the primary site?" (skull base
      2010;20:111-113).

PMID- 22470274
TI  - Long-term effects of self-control on alcohol use and sexual behavior among urban
      minority young women.
AB  - High risk alcohol use and sexual behaviors peak in young adulthood and often
      occur in the same individuals. Alcohol use has been found to impair decision
      making and contribute to high risk sexual activity. However, the association
      between alcohol use and risky sexual behavior may also reflect enduring
      individual differences in risk taking, sociability, self-control, and related
      variables. Both behaviors can serve similar functions related to recreation,
      interpersonal connection, and the pursuit of excitement or pleasure. The present
      study examined the extent to which high risk drinking and sexual behavior
      clustered together in a sample of urban minority young adult women, a demographic
      group at elevated risk for negative outcomes related to sexual health. We tested
      whether psychosocial functioning measured at the beginning of high school
      predicted classes of risk behaviors when girls were tracked longitudinally into
      young adulthood. Latent class analysis indicated three distinct profiles based on
      high risk drinking and sexual behavior (i.e., multiple sex partners) in young
      adulthood. The largest class (73% of the sample) reported low levels of risky
      drinking and sexual behavior. The next largest class (19%) reported high risk
      drinking and low risk sexual behavior, and the smallest class (8%) reported high
      levels of both behaviors. Compared to women from other racial/ethnic groups,
      black women were more likely to be categorized in the high risk drinking/low risk
      sex class. Multinomial logistic regression indicated that self-control in
      adolescence had a broad and enduring protective effect on risk behaviors eight
      years later and was associated with a greater probability of being in the low
      risk drinking/low risk sex class. Findings are discussed in terms of
      understanding the phenotypic expressions of risk behavior as they relate to early
      psychosocial development and the long-term protective function of self-control in
      reducing high risk drinking and sexual behaviors.

PMID- 22470275
TI  - Essential questions on suicide bereavement and postvention.
AB  - During the past decades public and research interest in postvention, i.e.,
      support for families and communities after a suicide, has increased. However, the
      postvention field is still facing a number of important challenges and questions.
      This article aims to discuss a series of essential issues on suicide bereavement
      and postvention, regarding the current state of the art and future developments.
      Who is a suicide survivor and how many suicide survivors are there? Is suicide
      bereavement different from other types of bereavement? What are the needs of
      suicide survivors and what is postvention from a clinical perspective and from a
      public health perspective? Can postvention be prevention? With this last
      question, the article concludes with a series of recommendations in order to
      strengthen the potential of postvention as prevention.

PMID- 22470276
TI  - Migration, agribusiness and nutritional status of children under five in
      Northwest Mexico.
AB  - The aim of this study was to examine the nutritional status of children of
      Mexican migrant worker families under five years of age within the context of
      global food markets. The sample included 404 children less than five years old
      from farms and agricultural communities in northwest Mexico. Prevalence of
      stunting and underweight of children appeared very similar to that of indigenous
      children from the national sample survey (difference 0.9 and 1.6 percentage
      points, respectively). Compared to the national sample of Mexican children,
      stunting and underweight seemed higher in migrant children (difference 17.7 and
      4.5 percentage points, respectively), but wasting, an indicator of both chronic
      and acute undernutrition, appeared to indicate a process of nutritional
      recuperation. Migrant children living in poverty and suffering from chronic
      undernutrition, poor performance and scarce education opportunities, can be
      expected to eventually become agricultural workers with low productivity and poor
      general health. Consumer's demands on social and environmental standards of fresh
      food production in developed countries could be an opportunity to impact the
      lives of migrant agricultural workers, their families and communities.

PMID- 22470277
TI  - Self-reported dental fear among dental students and their patients.
AB  - The aim of the present study was to compare self-reported dental fear among
      dental students and patients at a School of Dentistry in Belo Horizonte, Brazil.
      Eighty students ranging in age from 20 to 29 years and 80 patients ranging in age
      from 18 to 65 years participated in the study. A self-administered pre-tested
      questionnaire consisting of 13 items was used for data acquisition. The city of
      Belo Horizonte Social Vulnerability Index (SVI) was employed for socioeconomic
      classification. The chi-square test and binary and multinomial logistic
      regression were employed in the statistical analysis, with the significance level
      set at 0.05. The majority of dental students (76.5%) sought the dentist for the
      first time for a routine exam, while patients (77.3%) mostly sought a dentist for
      the treatment of dental pain. Dental fear was more prevalent among the patients
      (72.5%) than the students (27.5%). A total of 47.1% of the students and 52.9% of
      the patients reported having had negative dental experiences in childhood. The
      logistic model revealed an association between dental fear and a pain-related
      experience (OR: 1.8; 95%CI: 1.3-2.6). Patients were more prone to dental fear
      (OR: 2.2; 95%CI: 1.0-5.0). Although at different percentages, both students and
      patients experienced dental fear. Current patient with previous experience of
      dental pain had more dental fear.

PMID- 22470278
TI  - Governing for a healthy population: towards an understanding of how decision
      making will determine our global health in a changing climate.
AB  - Enhancing the adaptive capacity of individuals, communities, institutions and
      nations is pivotal to protecting and improving human health and well-being in the
      face of systemic social inequity plus dangerous climate change. However, research
      on the determinants of adaptive capacity in relation to health, particularly
      concerning the role of governance, is in its infancy. This paper highlights the
      intersections between global health, climate change and governance. It presents
      an overview of these key concerns, their relation to each other, and the
      potential that a greater understanding of governance may present opportunities to
      strengthen policy and action responses to the health effects of climate change.
      Important parallels between addressing health inequities and sustainable
      development practices in the face of global environmental change are also
      highlighted. We propose that governance can be investigated through two key
      lenses within the earth system governance theoretical framework; agency and
      architecture. These two governance concepts can be evaluated using methods of
      social network research and policy analysis using case studies and is the subject
      of further research.

PMID- 22470280
TI  - Implications of trauma among male and female offenders.

PMID- 22470279
TI  - Relative pesticide and exposure route contribution to aggregate and cumulative
      dose in young farmworker children.
AB  - The Child-Specific Aggregate Cumulative Human Exposure and Dose (CACHED)
      framework integrates micro-level activity time series with mechanistic exposure
      equations, environmental concentration distributions, and physiologically-based
      pharmacokinetic components to estimate exposure for multiple routes and
      chemicals. CACHED was utilized to quantify cumulative and aggregate exposure and
      dose estimates for a population of young farmworker children and to evaluate the
      model for chlorpyrifos and diazinon. Micro-activities of farmworker children
      collected concurrently with residential measurements of pesticides were used in
      the CACHED framework to simulate 115,000 exposure scenarios and quantify
      cumulative and aggregate exposure and dose estimates. Modeled metabolite urine
      concentrations were not statistically different than concentrations measured in
      the urine of children, indicating that CACHED can provide realistic biomarker
      estimates. Analysis of the relative contribution of exposure route and pesticide
      indicates that in general, chlorpyrifos non-dietary ingestion exposure accounts
      for the largest dose, confirming the importance of the micro-activity approach.
      The risk metrics computed from the 115,000 simulations, indicate that greater
      than 95% of these scenarios might pose a risk to children's health from aggregate
      chlorpyrifos exposure. The variability observed in the route and pesticide
      contributions to urine biomarker levels demonstrate the importance of accounting
      for aggregate and cumulative exposure in establishing pesticide residue
      tolerances in food.

PMID- 22470281
TI  - Implications of edentulism on quality of life among elderly.
AB  - This study aimed was to test the association between quality of life and
      edentulism among elderly individuals in a city in southeastern Brazil. This cross
      sectional study was carried out with 163 individuals aged 60 years or older,
      functionally independent and non-institutionalized. Data were collected with a
      questionnaire and oral examination. The edentulism was the dependent variable.
      The independent variables were sex, age, household income and quality of life
      (WHOQOL-Old) and their scores. To assess the association between the dependent
      variable and independent variables was used bivariate analysis (p < 0.10).
      Poisson regression model was performed, adjusting for age and sex. The average
      age of participants was 69 years (+/- 6.1), 68.7% were female and 52.8% were
      diagnosed as completely edentulous (90% CI: 0.33-1.24). When the independent
      variables were associated to the prevalence of edentulism, statistically
      significant associations were found for age (p = 0.03) and social participation
      dimension of the WHOQOL-Old (p = 0.08). In the Poisson regression, social
      participation remained statistically associated to edentulism {RP = 2.12 [90% CI
      (1.10-4.00)]}. The social participation proved to have a significant association
      to edentulism, thereby attesting to the negative effect of this condition on
      social aspects.

PMID- 22470282
TI  - Do parents still matter regarding adolescents' alcohol drinking? Experience from
      South Africa.
AB  - The purpose of this cross-sectional study was to improve our understanding of
      adolescents' perceptions of parental practices relating to their (adolescents')
      alcohol use. A total of 704 students were conveniently selected and completed
      self-administered questionnaires. More than half (54%) of the adolescents
      reported that they had consumed alcohol at some time in their life. Parental
      marital status was significantly associated with whether adolescents ever
      consumed alcohol or not (p < 0.05). A large number of mothers/female guardians
      (66.3%) and fathers/male guardians (69.3%) did not allow alcohol use at home.
      More mothers (54.6%) and fathers (65.3%) were not aware of their adolescents'
      alcohol consumption (p < 0.05). Adolescents were more likely to use alcohol when
      they reported that they had often seen either their father or mother drunk or
      both (p < 0.05). There were also significant associations between parents' views
      against alcohol use and their adolescents' alcohol use (p < 0.05). Prevalence of
      alcohol uptake was quite high among these adolescents. Compulsory parenting
      programmes and skills development should be practiced by education, health,
      cultural and religious groups. Parents should be motivated to delay the age at
      which their children are initiated into alcohol use and be provided with guidance
      on how to counteract social pressures.

PMID- 22470283
TI  - Media roles in suicide prevention: a systematic review.
AB  - The aim of the current systematic review was to monitor and provide an overview
      of the research performed about the roles of media in suicide prevention in order
      to find out possible effects media reporting on suicidal behaviours might have on
      actual suicidality (completed suicides, attempted suicides, suicidal ideation).
      The systematic review was performed following the principles of the PRISMA
      statement and includes 56 articles. Most of the studies support the idea that
      media reporting and suicidality are associated. However, there is a risk of
      reporting bias. More research is available about how irresponsible media reports
      can provoke suicidal behaviours (the 'Werther effect') and less about protective
      effect media can have (the 'Papageno effect'). Strong modelling effect of media
      coverage on suicide is based on age and gender. Media reports are not
      representative of official suicide data and tend to exaggerate sensational
      suicides, for example dramatic and highly lethal suicide methods, which are rare
      in real life. Future studies have to encounter the challenges the global medium
      Internet will offer in terms of research methods, as it is difficult to define
      the circulation of news in the Internet either spatially or in time. However,
      online media can provide valuable innovative qualitative research material.

PMID- 22470284
TI  - Removal of Escherichia coli and faecal coliforms from surface water and
      groundwater by household water treatment devices/systems: a sustainable solution
      for improving water quality in rural communities of the Southern African
      development community region.
AB  - There is significant evidence that household water treatment devices/systems
      (HWTS) are capable of dramatically improving microbially contaminated water
      quality. The purpose of this study was to examine five filters [(biosand filter
      standard (BSF-S); biosand filter-zeolite (BSF-Z); bucket filter (BF); ceramic
      candle filter (CCF); and silver-impregnated porous pot (SIPP)] and evaluate their
      ability to improve the quality of drinking water at the household level. These
      HWTS were manufactured in the workshop of the Tshwane University of Technology
      and evaluated for efficiency to remove turbidity, faecal coliforms and
      Escherichia coli from multiple water source samples, using standard methods. The
      flow rates ranged from 0.05 L/h to 2.49 L/h for SIPP, 1 L/h to 4 L/h for CCF,
      0.81 L/h to 6.84 L/h for BSF-S, 1.74 L/h to 19.2 L/h and 106.5 L/h to 160.5 L/h
      for BF The turbidity of the raw water samples ranged between 2.17 and 40.4 NTU.
      The average turbidity obtained after filtration ranged from 0.6 to 8 NTU (BSF-S),
      1 to 4 NTU (BSF-Z), 2 to 11 NTU (BF), and from 0.6 to 7 NTU (CCF) and 0.7 to 1
      NTU for SIPP. The BSF-S, BSF-Z and CCF removed 2 to 4 log(10) (99% to 100%) of
      coliform bacteria, while the BF removed 1 to 3 log (90% to 99.9%) of these
      bacteria. The performance of the SIPP in removing turbidity and indicator
      bacteria (>5 log(10), 100%) was significantly higher compared to that of the
      other HWTS (p < 0.05). The findings of this study indicate that the SIPP can be
      an effective and sustainable HWTS for the Southern African Development Community
      (SADC) rural communities, as it removed the total concentration of bacteria from
      test water, can be manufactured using locally available materials, and is easy to
      operate and to maintain.

PMID- 22470285
TI  - Zinc in well water and infant mortality in bangladesh: a report from
      gonoshasthaya kendra.
AB  - Zinc supplementation reduces the duration, severity and recurrence of diarrhoea
      in young children. This study examines whether zinc, found naturally in drinking
      water, reduced infant deaths from diarrhoea in rural Bangladesh. Information was
      compiled for births over two calendar years with follow-up for deaths within one
      year of birth. The study included 29,744 live births and 934 deaths in some 600
      villages under the care of Gonoshasthaya Kendra (GK), grouped into 15 health
      centre regions within 12 upazillas. Individual matching of death to birth data
      was not possible, but information on exposures through well water and on
      potential confounders was available for each upazilla. Average concentration of
      zinc in well water, reported by the British Geological Survey, was grouped into
      high (>0.07 mg/L), moderate (0.020-0.070 mg/L) and low (<0.020 mg/L)
      concentrations. Odds ratios (OR) were calculated for zinc by age and cause of
      death. Zinc concentration was unrelated to all-cause mortality but a decrease in
      deaths from diarrhoea (N = 50) was seen in areas with high zinc (OR = 0.30; 95%
      CI 0.13-0.69). No relation to diarrhoeal deaths was found with other well
      contaminants (arsenic, manganese) having accounted for zinc. Upazillas with a
      high proportion of women without education had higher rates of death from
      diarrhea, but the decrease in risk with high zinc remained (OR adjusted = 0.41;
      95% CI 0.20-0.84). It is concluded that exposure to zinc through drinking water
      may reduce risk of diarrhoeal deaths.

PMID- 22470286
TI  - Self-harm and suicide attempts among high-risk, urban youth in the U.S.: shared
      and unique risk and protective factors.
AB  - The extent to which self-harm and suicidal behavior overlap in community samples
      of vulnerable youth is not well known. Secondary analyses were conducted of the
      "linkages study" (N = 4,131), a cross-sectional survey of students enrolled in
      grades 7, 9, 11/12 in a high-risk community in the U.S. in 2004. Analyses were
      conducted to determine the risk and protective factors (i.e., academic grades,
      binge drinking, illicit drug use, weapon carrying, child maltreatment, social
      support, depression, impulsivity, self-efficacy, parental support, and parental
      monitoring) associated with both self-harm and suicide attempt. Findings show
      that 7.5% of participants reported both self-harm and suicide attempt, 2.2% of
      participants reported suicide attempt only, and 12.4% of participants reported
      self-harm only. Shared risk factors for co-occurring self-harm and suicide
      attempt include depression, binge drinking, weapon carrying, child maltreatment,
      and impulsivity. There were also important differences by sex, grade level, and
      race/ethnicity that should be considered for future research. The findings show
      that there is significant overlap in the modifiable risk factors associated with
      self-harm and suicide attempt that can be targeted for future research and
      prevention strategies.

PMID- 22470287
TI  - Do placebo response rates from cessation trials inform on strength of addictions?
AB  - There is an implied assumption that addictions to different substances vary in
      strength from weak (easier to stop) to strong (harder to stop), though explicit
      definitions are lacking. Our hypothesis is that the strength of addictions can be
      measured by cessation rates found with placebo or no treatment controls, and that
      a weaker addiction would have a higher cessation rate than a stronger addiction.
      We report an overview of systematic reviews and meta-analyses of cessation
      trials, using randomised or quasi-randomised trials and reporting objectively
      measured abstinence. The outcome for comparison was quit rates-typically the
      percentage of participants abstinent according to an objective test of abstinence
      at six months or longer. Twenty-eight cessation reviews (139,000 participants)
      were found. Most data came from reviews of smoking cessation in over 127,000
      participants, and other reviews each covered a few thousand participants. Few
      reviews used data from studies shorter than three months, and almost all
      determined abstinence using objective measures. Cessation rates with placebo in
      randomised trials using objective measures of abstinence and typically over six
      months duration were 8% for nicotine, 18% for alcohol, 47% for cocaine, and 44%
      for opioids. Evidence from placebo cessation rates indicates that nicotine is
      more difficult to give up than alcohol, cocaine, and opioids. Tobacco is also a
      severe addiction, with a number of major deleterious health effects in a large
      number of people.

PMID- 22470288
TI  - Secondhand tobacco smoke exposure and associated factors among college students
      on campus and in the home: a preliminary study.
AB  - To explore the prevalence of secondhand tobacco smoke (SHS) exposure of college
      students at two locations, i.e., on campus and in the home, and to identify
      factors associated with SHS exposure at each location, a preliminary cross
      sectional study was conducted on 1754 nonsmoking students from two universities
      in Korea. In total, 83.1% were exposed to SHS at least once a week on campus or
      at home; the average SHS exposure was 3.4 times per week. Specifically, 79.7% and
      23.5% were exposed to SHS on campus and in the home, respectively. On campus, SHS
      exposure was significantly more prevalent in freshmen and sophomore students. In
      the home, SHS exposure was significantly more prevalent among females, those with
      smokers in their families, and those who rated their health as poor. SHS exposure
      was common among nonsmoking college students, with more than two-thirds exposed
      on campus. The prevalence of SHS exposure was greater on campus than in the home;
      the factors associated with SHS exposure were location-specific.

PMID- 22470289
TI  - The relevance of personal characteristics in allocating health care resources
      controversial preferences of laypersons with different educational backgrounds.
AB  - In all industrial countries publicly funded health care systems are confronted
      with budget constraints. Therefore, priority setting in resource allocation seems
      inevitable. This paper examines whether personal characteristics could be taken
      into consideration when allocating health services in Germany, and whether
      attitudes towards prioritizing health care vary among individuals with different
      levels of education. Using a conjoint analysis approach, hypothetical patients
      described in terms of 'lifestyle', 'age', 'severity of illness', 'type of
      illness', 'improvement in health', and 'treatment costs' were constructed, and
      the importance weights for these personal characteristics were elicited from 120
      members of the general public. Participants were selected according to a sampling
      guide including educational background, age, chronic illness and gender. Results
      are reported for groups with different levels of education (low, middle, high)
      only. The findings show that the patients' age is the most important criterion
      for the allocation of health care resources, followed by 'severity of illness'
      and 'improvement in health'. Preferences vary among participants with different
      educational backgrounds, which refer to different attitudes towards distributive
      justice and might represent different socialization experiences.

PMID- 22470290
TI  - Cost-effective filter materials coated with silver nanoparticles for the removal
      of pathogenic bacteria in groundwater.
AB  - The contamination of groundwater sources by pathogenic bacteria poses a public
      health concern to communities who depend totally on this water supply. In the
      present study, potentially low-cost filter materials coated with silver
      nanoparticles were developed for the disinfection of groundwater. Silver
      nanoparticles were deposited on zeolite, sand, fibreglass, anion and cation resin
      substrates in various concentrations (0.01 mM, 0.03 mM, 0.05 mM and 0.1 mM) of
      AgNO(3). These substrates were characterised by SEM, EDS, TEM, particle size
      distribution and XRD analyses. In the first phase, the five substrates coated
      with various concentrations of AgNO(3) were tested against E. coli spiked in
      synthetic water to determine the best loading concentration that could remove
      pathogenic bacteria completely from test water. The results revealed that all
      filters were able to decrease the concentration of E. coli from synthetic water,
      with a higher removal efficiency achieved at 0.1 mM (21-100%) and a lower
      efficiency at 0.01 mM (7-50%) concentrations. The cation resin-silver
      nanoparticle filter was found to remove this pathogenic bacterium at the highest
      rate, namely 100%. In the second phase, only the best performing concentration of
      0.1 mM was considered and tested against presumptive E. coli, S. typhimurium, S.
      dysenteriae and V. cholerae from groundwater. The results revealed the highest
      bacteria removal efficiency by the Ag/cation resin filter with complete (100%)
      removal of all targeted bacteria and the lowest by the Ag/zeolite filter with an
      8% to 67% removal rate. This study therefore suggests that the filter system with
      Ag/cation resin substrate can be used as a potential alternative cost-effective
      filter for the disinfection of groundwater and production of safe drinking water.

PMID- 22470291
TI  - Temporal variation in air pollution concentrations and preterm birth-a population
      based epidemiological study.
AB  - There is growing evidence of adverse birth outcomes due to exposure to air
      pollution during gestation. However, recent negative studies are also reported.
      The aim of this study was to assess the effect of ozone and vehicle exhaust
      exposure (NO(2)) on the length of the gestational period and risk of preterm
      delivery. We used data from the Swedish Medical Birth Registry on all vaginally
      delivered singleton births in the Greater Stockholm area who were conceived
      during 1987-1995 (n = 115,588). Daily average levels of NO(2) (from three
      measuring stations) and ozone (two stations) were used to estimate trimester and
      last week of gestation average exposures. Linear regression models were used to
      assess the association between the two air pollutants and three exposure windows,
      while logistic regression models were used when analyzing associations with
      preterm delivery (<37 weeks gestation). Five percent were born preterm. The
      median gestational period was 40 weeks. Higher levels of ozone during the first
      trimester were associated with shorter gestation as well as with an elevated risk
      of preterm delivery, the odds ratio from the most complex model was 1.06 (95% CI:
      1.00-1.13) per 10 MUg/m(3) increase in the mean daily 8-h maximum concentration.
      Higher levels of ozone during the second trimester were associated with shorter
      gestation but the elevated risk of preterm delivery was not statistically
      significant. Higher levels of ozone and NO(2) during the last week of gestation
      were associated with a shorter duration of gestation and NO(2) also with preterm
      delivery. There were no significant associations between first and second
      trimester NO(2) exposure estimates and studied outcomes. The effect of first
      trimester ozone exposure, known to cause oxidative stress, was smallest among
      women who conceived during autumn when vitamin D status, important for fetal
      health, in Scandinavian women is the highest.

PMID- 22470292
TI  - The concept of equivalent radon concentration for practical consideration of
      indoor exposure to thoron.
AB  - To consider the total exposure to indoor radon and thoron, a concept of
      equivalent radon concentration for thoron is introduced, defined as the radon
      concentration that delivers the same annual effective dose as that resulting from
      the thoron concentration. The total indoor exposure to radon and thoron is then
      the sum of the radon concentration and the equivalent radon concentration for
      thoron. The total exposure should be compared to the radon guideline value, and
      if it exceeds the guideline value, appropriate remedial action is required. With
      this concept, a separate guideline for indoor thoron exposure is not necessary.
      For homes already tested for radon with radon detectors, Health Canada's
      recommendation of a 3-month radon test performed during the fall/winter heating
      season not only ensures a conservative estimate of the annual average radon
      concentration but also covers well any potentially missing contribution from
      thoron exposure. In addition, because the thoron concentration is much lower than
      the radon concentration in most homes in Canada, there is no real need to re-test
      homes for thoron.

PMID- 22470293
TI  - Sport fields as potential catalysts for physical activity in the neighbourhood.
AB  - Physical activity is associated with access to recreational facilities such as
      sports fields. Because it is not clear whether objectively- or subjectively
      assessed access to facilities exerts a stronger influence on physical activity,
      we investigated the association between the objective and perceived accessibility
      of sport fields and the levels of self-reported physical activity among adults in
      Edmonton, Canada. A sample of 2879 respondents was surveyed regarding their socio
      demographics, health status, self-efficacy, levels of physical activity, as well
      as their perceptions of built environment in relation to physical activity.
      Neighbourhood-level data were obtained for each respondent based on their
      residence. Accessibility to facilities was assessed using the enhanced Two-Step
      Floating Catchment Area method. Geographic Information Systems were employed. A
      logistic regression was performed to predict physical activity using individual-
      and neighbourhood-level variables. Women, older individuals, and individuals with
      higher educational attainment were less likely to be physically active. Also,
      individuals with higher self-efficacy and higher objectively-assessed access to
      facilities were more likely to be physically active. Interventions that integrate
      provision of relevant programs for various population groups and of improved
      recreational facilities may contribute to sport fields becoming catalysts for
      physical activity by generating movement both on the site and in the
      neighbourhood.

PMID- 22470294
TI  - Changes in physical fitness, bone mineral density and body composition during
      inpatient treatment of underweight and normal weight females with longstanding
      eating disorders.
AB  - The purpose of this study was to examine changes in aerobic fitness, muscular
      strength, bone mineral density (BMD) and body composition during inpatient
      treatment of underweight and normal weight patients with longstanding eating
      disorders (ED). Twenty-nine underweight (BMI < 18.5, n = 7) and normal weight
      (BMI >= 18.5, n = 22) inpatients (mean (SD) age: 31.0 (9.0) years, ED duration:
      14.9 (8.8) years, duration of treatment: 16.6 (5.5) weeks) completed this
      prospective naturalistic study. The treatment consisted of nutritional
      counseling, and 2 * 60 min weekly moderate intensive physical activity in
      addition to psychotherapy and milieu therapy. Underweight patients aimed to
      increase body weight with 0.5 kg/week until the weight gain goal was reached.
      Aerobic fitness, muscular strength, BMD and body composition were measured at
      admission and discharge. Results showed an increase in mean muscular strength,
      total body mass, fat mass, and body fat percentage, but not aerobic capacity,
      among both underweight and normal weight patients. Lumbar spine BMD increased
      among the underweight patients, no changes were observed in BMD among the normal
      weight patients. Three out of seven underweight patients were still underweight
      at discharge, and only three out of nine patients with excessive body fat (i.e.,
      >33%) managed to reduce body fat to normal values during treatment. These results
      calls for a more individualized treatment approach to achieve a more optimal body
      composition among both underweight and normal to overweight patients with
      longstanding ED.

PMID- 22470295
TI  - Tobacco use, exposure to secondhand smoke, and cessation counseling among health
      professions students: greek data from the global health professions student
      Survey (GHPSS).
AB  - We conducted the GHPSS (Global Health Professions Student Survey) to obtain
      information regarding health profession students' smoking habits and perceptions,
      exposure to secondhand smoke (SHS) as well as level of knowledge and training on
      tobacco use and smoking cessation counseling. GHPSS is a survey for third-year
      students in the following fields: health visitors, dentistry, medicine, nursing
      and/or pharmacy. The highest tobacco use prevalence rate and exposure to SHS were
      recorded among health visitor students with 46.4% and 33.3% respectively. The
      majority of the respondents believed that their profession serves as a role model
      for their patients. Formal training on cessation counseling ranged between 10.7%
      for health visitor students to 22.4% for nursing students. The relatively high
      percentage of health profession students who currently smoke and the alarmingly
      high percentage of those exposed to SHS indicate lack of concerted efforts for
      implementation and effective enforcement of the anti-tobacco policy measures.
      Despite its significance, formal training on cessation counseling for students is
      strikingly low. These results indicate the urgent need to train health
      professional students on tobacco cessation counseling and educate them on the
      dangers of tobacco use, SHS and the positively influential role they can play to
      affect their patients' smoking habits.

PMID- 22470296
TI  - Checklist model to improve work practices in small-scale demolition operations
      with silica dust exposures.
AB  - A systematic approach was developed to review, revise and adapt existing exposure
      control guidance used in developed countries for use in developing countries. One
      page employee and multiple-page supervisor guidance sheets were adapted from
      existing documents using a logic framework and workers were trained to use the
      information to improve work practices. Interactive, hands-on training was
      delivered to 26 workers at five small-scale demolition projects in Maputo City,
      Mozambique, and evaluated. A pre-and-post walkthrough survey used by trained
      observers documented work practice changes. Worker feedback indicated that the
      training was effective and useful. Workers acquired knowledge (84% increase, p <
      0.01) and applied the work practice guidance. The difference of proportions
      between use of work practice components before and after the intervention was
      statistically significant (p < 0.05). Changes in work practices following
      training included preplanning, use of wet methods and natural ventilation and end
      of-task review. Respirable dust measurements indicated a reduction in exposure
      following training. Consistency in observer ratings and observations support the
      reliability and validity of the instruments. This approach demonstrated the short
      term benefit of training in changing work practices; follow-up is required to
      determine the long-term impact on changes in work practices, and to evaluate the
      need for refresher training.

PMID- 22470297
TI  - The skin ivory spot. A possible indicator for skinfield photo-carcinogenesis in
      recreational sunbed addicts.
AB  - INTRODUCTION: For a decade or so, artificial sources of restricted light
      wavelengths, particularly sunbeds, have progressively gained popularity among
      adolescents and young adults. Warnings were raised focusing on the risk of
      accelerated photoaging and photocarcinogenesis. The ULEV (ultraviolet light
      enhanced visualization) method is a convenient noninvasive way identifying subtle
      pigmentary changes presenting as a mottled subclinical melanoderma (MSM). Of
      note, rare spotty amelanotic macules presenting as skin ivory spots (SIS) was
      reported on any part of the body. SUBJECTS AND METHOD: This work is the first
      attempt at evaluating the changes in the MSM and SIS spots developed on the skin
      of 33 phototype III young women designated as avid users involved in frequent
      exposures to sunshine and sunbeds for lifestyle purposes for a duration of at
      least 120 months. RESULTS: MSM was markedly heterogeneous and was distinctly
      obvious in the majority of adepts of frequent natural and artificial
      photoexposures. SIS was particularly developed in subjects presenting with severe
      MSM patterns. DISCUSSION: MSM and SIS are more severe in subjects frequently
      exposed to sunbeds and sun exposures. These signs possibly represent a risk
      marker for field photocarcinogenesis.

PMID- 22470298
TI  - Cumulative risk assessment: an overview of methodological approaches for
      evaluating combined health effects from exposure to multiple environmental
      stressors.
AB  - Systematic evaluation of cumulative health risks from the combined effects of
      multiple environmental stressors is becoming a vital component of risk-based
      decisions aimed at protecting human populations and communities. This article
      briefly examines the historical development of cumulative risk assessment as an
      analytical tool, and discusses current approaches for evaluating cumulative
      health effects from exposure to both chemical mixtures and combinations of
      chemical and nonchemical stressors. A comparison of stressor-based and effects
      based assessment methods is presented, and the potential value of focusing on
      viable risk management options to limit the scope of cumulative evaluations is
      discussed. The ultimate goal of cumulative risk assessment is to provide answers
      to decision-relevant questions based on organized scientific analysis; even if
      the answers, at least for the time being, are inexact and uncertain.

PMID- 22470299
TI  - Physical activity and risk of cardiovascular disease--a meta-analysis of
      prospective cohort studies.
AB  - In order to update and improve available evidence on associations of physical
      activity (PA) with cardiovascular disease (CVD) by applying meta-analytic random
      effects modeling to data from prospective cohort studies, using high quality
      criteria of study selection, we searched the PubMed database from January 1980 to
      December 2010 for prospective cohort studies of PA and incident CVD,
      distinguishing occupational PA and leisure time PA, coronary heart disease (CHD)
      and stroke, respectively. Inclusion criteria were peer-reviewed English papers
      with original data, studies with large sample size (n >= 1,000) and substantial
      follow-up (>= 5 years), available data on major confounders and on estimates of
      relative risk (RR) or hazard ratio (HR), with 95% confidence intervals (CI). We
      included 21 prospective studies in the overall analysis, with a sample size of
      more than 650,000 adults who were initially free from CVD, and with some 20,000
      incident cases documented during follow-up. Among men, RR of overall CVD in the
      group with the high level of leisure time PA was 0.76 (95% CI 0.70-0.82, p <
      0.001), compared to the reference group with low leisure time PA, with obvious
      dose-response relationship. A similar effect was observed among women (RR = 0.73,
      95% CI 0.68-0.78, p < 0.001). A strong protective effect of occupational PA was
      observed for moderate level in both men (RR = 0.89, 95% CI 0.82-0.97, p = 0.008)
      and women (RR = 0.83, 95% CI 0.67-1.03, p = 0.089). No publication bias was
      observed. Our findings suggest that high level of leisure time PA and moderate
      level of occupational PA have a beneficial effect on cardiovascular health by
      reducing the overall risk of incident coronary heart disease and stroke among men
      and women by 20 to 30 percent and 10 to 20 percent, respectively. This evidence
      from high quality studies supports efforts of primary and secondary prevention of
      CVD in economically advanced as well as in rapidly developing countries.

PMID- 22470300
TI  - The role of maternal smoking in effect of fetal growth restriction on poor
      scholastic achievement in elementary school.
AB  - Fetal growth restriction and maternal smoking during pregnancy are independently
      implicated in lowering intellectual attainment in children. We hypothesized that
      only reduction of fetal growth that is attributable to extrinsic causes (e.g.,
      maternal smoking) affects intellectual development of a child. Cross-sectional
      survey of 3,739 students in Nova Scotia (Canada) in 2003 was linked with the
      perinatal database, parental interviews on socio-demographic factors and the
      performance on standardized tests when primarily 11-12 years of age, thereby
      forming a retrospective cohort. Data was analyzed using hierarchical logistic
      regression with correction for clustering of children within schools. The risk of
      poor test result among children born small-for-gestational-age (SGA) to mothers
      who smoked was 29.4%, higher than in any other strata of maternal smoking and
      fetal growth. The adjusted odds ratio among SGA children born to mothers who
      smoked was the only one elevated compared to children who were not growth
      restricted and born to mothers who did not smoke (17.0%, OR = 1.46, 95% CI 1.02,
      2.09). Other perinatal, maternal and socio-demographic factors did not alter this
      pattern of effect modification. Heterogeneity of etiology of fetal growth
      restriction should be consider in studies that address examine its impact on
      health over life course.

PMID- 22470301
TI  - Nutritional rehabilitation of HIV-exposed infants in Malawi: results from the
      drug resources enhancement against AIDS and malnutrition program.
AB  - Infant malnutrition in sub-Saharan Africa is a public health priority and a
      challenge in high HIV prevalence areas. The Drug Resources Enhancement Against
      AIDS and Malnutrition program, with multiple medical centers in Sub-Saharan
      Africa, developed an innovative intervention for the surveillance and control of
      malnutrition. In a pilot initiative, 36 HIV-exposed children were evaluated at
      baseline upon presentation for malnutrition and at six months post- treatment.
      Parameters included HIV-free survival, nutritional status and change in diet.
      Food diary data was entered and processed using the Nutrisurvey (WHO) software.
      At 6 months post-intervention, a significant improvement in anthropometric
      parameters was noted. Slowing of linear growth was observed in patients with
      malaria with a mean gain in centimetres of 4.4 +/- 1.7 as compared to 5.6 +/- 1.7
      in children with no malaria, p < 0.048 (CL 95%: -2.32, -0.01). Dietary diversity
      scores increased from 5.3 +/- 1.9 to 6.5 +/- 1.3, p < 0.01 at 6 months. A
      significant increase (+25%, p < 0.02) in the number of children eating fish meals
      was noted. Our pilot data describes positive outcomes from a rehabilitative
      nutritional approach based on use of local foods, peer education, anthropometric
      and clinical monitoring in areas of high food insecurity. The relationship
      between malaria and linear growth retardation requires further investigation.

PMID- 22470302
TI  - Building climate resilience in the Blue Nile/Abay Highlands: a role for Earth
      system sciences.
AB  - The Blue Nile (Abay) Highlands of Ethiopia are characterized by significant
      interannual climate variability, complex topography and associated local climate
      contrasts, erosive rains and erodible soils, and intense land pressure due to an
      increasing population and an economy that is almost entirely dependent on
      smallholder, low-input agriculture. As a result, these highland zones are highly
      vulnerable to negative impacts of climate variability. As patterns of variability
      and precipitation intensity alter under anthropogenic climate change, there is
      concern that this vulnerability will increase, threatening economic development
      and food security in the region. In order to overcome these challenges and to
      enhance sustainable development in the context of climate change, it is necessary
      to establish climate resilient development strategies that are informed by best
      available Earth System Science (ESS) information. This requirement is complicated
      by the fact that climate projections for the Abay Highlands contain significant
      and perhaps irreducible uncertainties. A critical challenge for ESS, then, is to
      generate and to communicate meaningful information for climate resilient
      development in the context of a highly uncertain climate forecast. Here we report
      on a framework for applying ESS to climate resilient development in the Abay
      Highlands, with a focus on the challenge of reducing land degradation.

PMID- 22470303
TI  - Suicidal ideation and associated factors among school-going adolescents in
      Thailand.
AB  - The aim of this study was to estimate the prevalence and identify associations
      between suicidal ideation and indicators of psychosocial distress and social
      environmental factors in Thai adolescents. Using data from the Thailand Global
      School-Based Student Health Survey (GSHS) 2008, we assessed the prevalence of
      suicidal ideation and its associated factors among adolescents (N = 2,758).
      Overall the prevalence of suicidal ideation in the past 12 months was 8.8% (9.9%
      males and 7.7% females). Variables influenced the suicidal ideation in
      multivariable analysis were sadness (Odds Ratio = OR: 6.03; 95% Confidence
      Interval = CI (3.00-12.14), lack of parental attachment (OR = 2.26, CI = 1.09
      4.67), current alcohol use (OR = 2.32, 1.21-4.44), and ever having had sexual
      intercourse (OR = 4.16, CI = 3.40-7.68). Psychosocial, health-risk behaviours and
      lack of protective factors appear to effect suicidal ideation in this youth
      population.

PMID- 22470304
TI  - Microtubules as a critical target for arsenic toxicity in lung cells in vitro and
      in vivo.
AB  - To understand mechanisms for arsenic toxicity in the lung, we examined effects of
      sodium m-arsenite (As3+) on microtubule (MT) assembly in vitro (0-40 uM), in
      cultured rat lung fibroblasts (RFL6, 0-20 uM for 24 h) and in the rat animal
      model (intratracheal instillation of 2.02 mg As/kg body weight, once a week for 5
      weeks). As3+ induced a dose-dependent disassembly of cellular MTs and enhancement
      of the free tubulin pool, initiating an autoregulation of tubulin synthesis
      manifest as inhibition of steady-state mRNA levels of betaI-tubulin in dosed lung
      cells and tissues. Spindle MT injuries by As3+ were concomitant with chromosomal
      disorientations. As3+ reduced the binding to tubulin of [3H]N-ethylmaleimide
      (NEM), an -SH group reagent, resulting in inhibition of MT polymerization in
      vitro with bovine brain tubulins which was abolished by addition of
      dithiothreitol (DTT) suggesting As3+ action upon tubulin through -SH groups. In
      response to As3+, cells elevated cellular thiols such as metallothionein. Taxol,
      a tubulin polymerization agent, antagonized both As3+ and NEM induced MT
      depolymerization. MT-associated proteins (MAPs) essential for the MT stability
      were markedly suppressed in As3+-treated cells. Thus, tubulin sulfhydryls and
      MAPs are major molecular targets for As3+ damage to the lung triggering MT
      disassembly cascades.

PMID- 22470305
TI  - The effect of computer usage in internet cafe on cigarette smoking and alcohol
      use among chinese adolescents and youth: a longitudinal study.
AB  - We used longitudinal data to investigate the relationship between computer use in
      internet cafes and smoking/drinking behavior among Chinese adolescents and young
      adults. Data are from two waves of the China Health and Nutrition Survey (2004
      and 2006). Fixed effects models were used to examine if changes in internet cafe
      use were associated with changes in cigarette smoking and drinking of alcohol.
      Male cafe users spent on average 17.3 hours in front of the computer/week. This
      was associated with an increase in the probability of being a current smoker by
      13.3% and with smoking 1.7 more cigarettes. Female cafe users spent on average 11
      hours on the computer/week. This was associated with an increase in the
      probability of drinking wine and/or liquor by 14.74% and was not associated with
      smoking. Internet cafes are an important venue by which adolescent and young
      adults in China are exposed to smoking and drinking. Multi-component
      interventions are needed ranging from policies regulating cigarette and alcohol
      availability in these venues to anti-tobacco campaigns aimed at the general
      population but also at individuals who frequent these establishments.

PMID- 22470306
TI  - Mineral contamination from cemetery soils: case study of Zandfontein Cemetery,
      South Africa.
AB  - The burial of coffins may pose an environmental and health hazard since the
      metals that are used in coffin-making may corrode or degrade into harmful toxins.
      These may leach into the surrounding soils and groundwater. Very little research
      has been conducted world-wide on the mineral contamination potential of
      cemeteries, and virtually none in South Africa. The aim of the study is to
      determine whether burial practices affect the mineral content of soils in
      cemeteries. This was done by comparing the mineral concentrations of soils within
      the Zandfontein Cemetery in Tshwane (Gauteng, South Africa) to those off-site as
      well as those in zones with high burial loads with those zones with fewer
      burials. Twenty three soil samples were collected from various sites on- and off
      site and analyzed for 31 minerals using ICP-AES. It was found that mineral
      concentrations of soils within the Zandfontein Cemetery were considerably higher
      than those off-site. Soil samples in multiple burials blocks also have elevated
      metal concentrations. These excess metals are probably of anthropogenic origin
      associated with burial practices and could pose an environmental and human health
      hazard. Strict monitoring of water quality in boreholes in the vicinity of the
      cemetery is recommended.

PMID- 22470307
TI  - Age, gender and suicidal ideation following voluntary HIV counseling and testing.
AB  - The aim of this study was to determine the prevalence of suicidal ideation in
      patients who were tested for HIV-infection and whether along with their HIV
      status, age and gender influenced their risk for suicidal ideation. The sample
      consisted of 189 patients who attended a voluntary HIV counseling and testing
      clinic (VCT) at a general state hospital in Durban, South Africa. Their mean age
      at baseline was 34.2 years, with an age range of between 16-79 years.
      Seropositivity, age and gender were significantly associated with suicidal
      ideation. The majority of these patients were in the younger age group, and young
      males had a 1.8 times higher risk for suicidal ideation than females. Although
      risk factors for seropositive-related suicidal ideation can be complex and multi
      factorial, this study identified a young age and male gender as important high
      risk factors in the sample studied. It is recommended that all, but especially
      young male HIV-infected patients seen at a VCT clinic be screened for suicidal
      ideation and that early intervention to prevent subsequent suicides or suicidal
      attempts be included in pre- and post-test HIV counseling.

PMID- 22470309
TI  - Application of porous nickel-coated TiO2 for the photocatalytic degradation of
      aqueous quinoline in an internal airlift loop reactor.
AB  - P25 film, prepared by a facile dip-coating method without any binder, was further
      developed in a recirculating reactor for quinoline removal from synthetic
      wastewater. Macroporous foam Ni, which has an open three-dimensional network
      structure, was utilized as a substrate to make good use of UV rays. Field
      emission scanning electron microscopy and X-ray diffraction analysis showed that
      the coated/calcinated P25 films consisted of two crystal phases, and had a number
      of uniform microcracks on the surface. The effects of initial quinoline
      concentration, light intensity, reaction temperature, aeration, and initial pH
      were studied. Increased reaction time, light intensity, environmental
      temperature, and gas aeration were found to significantly improve the quinoline
      removal efficiency. The aeration effect of oxygen dependency on the quinoline
      degradation had the trend pure oxygen > air > no gas > pure nitrogen with free
      O2. The solution pH crucially affected quinoline photodegradation; the high
      electrostatic adsorption of quinoline molecules on the TiO2 surface was strongly
      pH dependent. 2-Pyridine-carboxaldehyde, 3-pyridinecarboxaldehyde, and 2(1H)
      quinolinone were identified as the major intermediates of quinoline degradation.
      Based on these intermediates, a primary degradation mechanism was proposed. This
      reusable P25 film benefits the photodegradation of water contaminants and has
      potential in other various applications.

PMID- 22470308
TI  - Seasonality of suicidal behavior.
AB  - A seasonal suicide peak in spring is highly replicated, but its specific cause is
      unknown. We reviewed the literature on suicide risk factors which can be
      associated with seasonal variation of suicide rates, assessing published articles
      from 1979 to 2011. Such risk factors include environmental determinants,
      including physical, chemical, and biological factors. We also summarized the
      influence of potential demographic and clinical characteristics such as age,
      gender, month of birth, socioeconomic status, methods of prior suicide attempt,
      and comorbid psychiatric and medical diseases. Comprehensive evaluation of risk
      factors which could be linked to the seasonal variation in suicide is important,
      not only to identify the major driving force for the seasonality of suicide, but
      also could lead to better suicide prevention in general.

PMID- 22470310
TI  - Knowledge of health effects and intentions to quit among smokers in India:
      findings from the Tobacco Control Policy (TCP) India pilot survey.
AB  - Awareness of the health risks of smoking is an important factor in predicting
      smoking-related behaviour; however, little is known about the knowledge of health
      risks in low-income countries such as India. The present study examined beliefs
      about the harms of smoking and the impact of health knowledge on intentions to
      quit among a sample of 249 current smokers in both urban and rural areas in two
      states (Maharashtra and Bihar) from the 2006 TCP India Pilot Survey, conducted by
      the ITC Project. The overall awareness among smokers in India of the specific
      health risks of smoking was very low compared to other ITC countries, and only
      10% of respondents reported that they had plans to quit in the next six months.
      In addition, smokers with higher knowledge were significantly more likely to have
      plans to quit smoking. For example, 26.2% of respondents who believed that
      smoking cause CHD and only 5.5% who did not believe that smoking causes CHD had
      intentions to quit (chi2 = 16.348, p < 0.001). Important differences were also
      found according to socioeconomic factors and state: higher levels of knowledge
      were found in Maharashtra than in Bihar, in urban compared to rural areas, among
      males, and among smokers with higher education. These findings highlight the need
      to increase awareness about the health risks of smoking in India, particularly in
      rural areas, where levels of education and health knowledge are lower.

PMID- 22470311
TI  - The association between community stressors and asthma prevalence of school
      children in Winnipeg, Canada.
AB  - It is generally surmised that community stressors have an incubating effect for a
      variety of diagnoses on maternal and child health. This is of public health
      significance, as children of mothers facing long-term distress were found to have
      a 60% higher risk for asthma diagnosis at age 7 in Manitoba, Canada. Our
      objective was to determine the association of community stressors with childhood
      asthma prevalence in Winnipeg, Canada from participants who completed the Study
      of Asthma, Genes and the Environment (SAGE) survey administered in 2002-2003 to a
      birth cohort from 1995. Measures of community socioeconomic makeup and community
      disorder with rank ordinalized by quintile at the census tract level were
      obtained from the 1996 Canada Census. Crime data (annual incidence per 10,000
      persons) by neighbourhood profile for 2001 was provided by the Winnipeg Police
      Service. Dichotomous caregiver report of child asthma along with other indicators
      from the geocoded SAGE survey allowed linkage to 23 neighbourhood profiles.
      Multilevel logistic regression analyses were performed to estimate the effect of
      community stressors on childhood asthma prevalence for birth and non-birth home
      children (N = 1472) and children resident of birth homes at age 7 or 8 (N = 698).
      After adjusting for individual risk factors, children resident of birth homes in
      a high thefts over $5,000 neighbourhood profile were twice as likely (Adjusted
      OR, 2.05; 95% CI, 1.11-3.81) to have report of asthma compared to children in a
      lower thefts over $5,000 profile, with community thefts over $5,000 explaining
      over half of the observed neighbourhood variation in asthma.

PMID- 22470312
TI  - Correlates of suicide ideation and attempt among youth living in the slums of
      Kampala.
AB  - While suicidal behavior is recognized as a growing public health problem world
      wide, little is known about the prevalence and risk factors for suicidal
      behaviors among street and slum youth in Africa, and in Uganda, specifically. The
      number of youth who live on the streets and in the slums of Kampala appears to be
      growing rapidly, but their mental health needs have not been documented, which
      has hampered resource allocation and service implementation. This study of youth,
      ages 14-24, was conducted in May and June of 2011, to assess the prevalence and
      correlates of suicidal behavior. Participants (N = 457) were recruited for a 30
      minute interviewer-administered survey through eight drop-in centers operated by
      the Uganda Youth Development Link for youth in need of services. Bivariate and
      multivariate logistic regression analyses were computed to determine associations
      between psychosocial correlates and suicide ideation and suicide attempt.
      Reporting both parents deceased Adj.OR = 2.36; 95% CI: 1.23-4.52), parental
      neglect due to alcohol use (Adj.OR = 2.09; 95% CI: 1.16-3.77), trading sex for
      food, shelter or money (Adj.OR = 1.95; 95% CI: 1.09-3.51), sadnesss (Adj.OR =
      2.42; 95% CI: 1.20-4.89), loneliness (Adj.OR = 2.67; 95% CI: 1.12-6.40) and
      expectations of dying prior to age 30 (Adj.OR = 2.54; 95% CI: 1.53-4.23) were
      significantly associated with suicide ideation in multivariate analyses. Parental
      neglect due to alcohol use (Adj.OR = 2.04; 95% CI: 1.11-3.76), sadness (Adj.OR =
      2.42; 95% CI: 1.30-7.87), and expectations of dying prior to age 30 (Adj.OR =
      2.18; 95% CI: 1.25-3.79) were significantly associated with suicide attempt in
      multivariate analyses. Given the dire circumstances of this vulnerable
      population, increased services and primary prevention efforts to address the risk
      factors for suicidal behavior are urgently needed.

PMID- 22470313
TI  - Building climate resilience in the Blue Nile/Abay Highlands: a framework for
      action.
AB  - Ethiopia has become warmer over the past century and human induced climate change
      will bring further warming over the next century at unprecedented rates. On the
      average, climate models show a tendency for higher mean annual rainfall and for
      wetter conditions, in particular during October, November and December, but there
      is much uncertainty about the future amount, distribution, timing and intensity
      of rainfall. Ethiopia's low level of economic development, combined with its
      heavy dependence on agriculture and high population growth rate make the country
      particularly susceptible to the adverse effects of climate change. Nearly 90% of
      Ethiopia's population lives in the Highlands, which include the critical Blue
      Nile (Abay) Highlands--a region that holds special importance due to its role in
      domestic agricultural production and international water resources. A five year
      study of climate vulnerability and adaptation strategies in communities of Choke
      Mountain, located in the center of the Abay Highlands, has informed a proposed
      framework for enhancing climate resilience in communities across the region. The
      framework is motivated by the critical need to enhance capacity to cope with
      climate change and, subsequently, to advance a carbon neutral and climate
      resilient economy in Ethiopia. The implicit hypothesis in applying a research
      framework for this effort is that science-based information, generated through
      improved understanding of impacts and vulnerabilities of local communities, can
      contribute to enhanced resilience strategies. We view adaptation to climate
      change in a wider context of changes, including, among others, market conditions,
      the political-institutional framework, and population dynamics. From a livelihood
      perspective, culture, historical settings, the diversity of income generation
      strategies, knowledge, and education are important factors that contribute to
      adaptive capacities. This paper reviews key findings of the Choke Mountain study,
      describes the principles of the climate resilience framework, and proposes an
      implementation strategy for climate resilient development to be applied in the
      Abay Highlands, with potential expansion to agricultural communities across the
      region and beyond.

PMID- 22470314
TI  - Comparison of BMI derived from parent-reported height and weight with measured
      values: results from the German KiGGS study.
AB  - The use of parent-reported height and weight is a cost-efficient instrument to
      assess the prevalence of children's weight status in large-scale surveys. This
      study aimed to examine the accuracy of BMI derived from parent-reported height
      and weight and to identify potential predictors of the validity of BMI derived
      from parent-reported data. A subsample of children aged 2-17 years (n = 9,187)
      was taken from the 2003-2006 cross-sectional German KiGGS study. Parent-reported
      and measured height and weight were collected and BMI was calculated. Besides
      descriptive analysis, linear regression models with BMI difference and logistic
      regression models with weight status misclassification as dependent variables
      were calculated. Height differences varied by gender and were generally small.
      Weight and BMI were under-reported in all age groups, the under-reporting getting
      stronger with increasing age. Overall, the proportion for overweight and obesity
      based on parental and measured reports differed slightly. In the youngest age
      group, the proportion of overweight children was overestimated, while it was
      underestimated for older children and adolescents. Main predictors of the
      difference between parent reported and measured values were age, gender, weight
      status and parents' perception of the child's weight. In summary, the exclusive
      use of uncorrected parental reports for assessment of prevalence rates of weight
      status is not recommended.

PMID- 22470315
TI  - A screening method for assessing cumulative impacts.
AB  - The California Environmental Protection Agency (Cal/EPA) Environmental Justice
      Action Plan calls for guidelines for evaluating "cumulative impacts." As a first
      step toward such guidelines, a screening methodology for assessing cumulative
      impacts in communities was developed. The method, presented here, is based on the
      working definition of cumulative impacts adopted by Cal/EPA: "Cumulative impacts
      means exposures, public health or environmental effects from the combined
      emissions and discharges in a geographic area, including environmental pollution
      from all sources, whether single or multi-media, routinely, accidentally, or
      otherwise released. Impacts will take into account sensitive populations and
      socio-economic factors, where applicable and to the extent data are available."
      The screening methodology is built on this definition as well as current
      scientific understanding of environmental pollution and its adverse impacts on
      health, including the influence of both intrinsic, biological factors and non
      intrinsic socioeconomic factors in mediating the effects of pollutant exposures.
      It addresses disparities in the distribution of pollution and health outcomes.
      The methodology provides a science-based tool to screen places for relative
      cumulative impacts, incorporating both the pollution burden on a community-
      including exposures to pollutants, their public health and environmental effects-
      and community characteristics, specifically sensitivity and socioeconomic
      factors. The screening methodology provides relative rankings to distinguish more
      highly impacted communities from less impacted ones. It may also help identify
      which factors are the greatest contributors to a community's cumulative impact.
      It is not designed to provide quantitative estimates of community-level health
      impacts. A pilot screening analysis is presented here to illustrate the
      application of this methodology. Once guidelines are adopted, the methodology can
      serve as a screening tool to help Cal/EPA programs prioritize their activities
      and target those communities with the greatest cumulative impacts.

PMID- 22470317
TI  - Does the mucosa activate or modulate the neural circuits controlling colonic
      motility?

PMID- 22470318
TI  - Circadian rhythms and memory formation: regulation by chromatin remodeling.
AB  - Epigenetic changes, such as DNA methylation or histone modification, can remodel
      the chromatin and regulate gene expression. Remodeling of chromatin provides an
      efficient mechanism of transducing signals, such as light or nutrient
      availability, to regulate gene expression. CLOCK:BMAL1 mediated activation of
      clock-controlled genes (CCGs) is coupled to circadian changes in histone
      modification at their promoters. Several chromatin modifiers, such as the
      deacetylases SIRT1 and HDAC3 or methyltransferase MLL1, have been shown to be
      recruited to the promoters of the CCGs in a circadian manner. Interestingly, the
      central element of the core clock machinery, the transcription factor CLOCK, also
      possesses histone acetyltransferase activity. Rhythmic expression of the CCGs is
      abolished in the absence of these chromatin modifiers. Recent research has
      demonstrated that chromatin remodeling is at the cross-roads of circadian rhythms
      and regulation of metabolism and aging. It would be of interest to identify if
      similar pathways exist in the epigenetic regulation of memory formation.

PMID- 22470316
TI  - The nervous system and metabolic dysregulation: emerging evidence converges on
      ketogenic diet therapy.
AB  - A link between metabolism and brain function is clear. Since ancient times,
      epileptic seizures were noted as treatable with fasting, and historical
      observations of the therapeutic benefits of fasting on epilepsy were confirmed
      nearly 100 years ago. Shortly thereafter a high fat, low-carbohydrate ketogenic
      diet (KD) debuted as a therapy to reduce seizures. This strict regimen could
      mimic the metabolic effects of fasting while allowing adequate caloric intake for
      ongoing energy demands. Today, KD therapy, which forces predominantly ketone
      based rather than glucose-based metabolism, is now well-established as highly
      successful in reducing seizures. Cellular metabolic dysfunction in the nervous
      system has been recognized as existing side-by-side with nervous system disorders
      - although often with much less obvious cause-and-effect as the relationship
      between fasting and seizures. Rekindled interest in metabolic and dietary
      therapies for brain disorders complements new insight into their mechanisms and
      broader implications. Here we describe the emerging relationship between a KD and
      adenosine as a way to reset brain metabolism and neuronal activity and disrupt a
      cycle of dysfunction. We also provide an overview of the effects of a KD on
      cognition and recent data on the effects of a KD on pain, and explore the
      relative time course quantified among hallmark metabolic changes, altered neuron
      function and altered animal behavior assessed after diet administration. We
      predict continued applications of metabolic therapies in treating dysfunction
      including and beyond the nervous system.

PMID- 22470319
TI  - Neurons derived from human embryonic stem cells extend long-distance axonal
      projections through growth along host white matter tracts after intra-cerebral
      transplantation.
AB  - Human pluripotent stem cells have the capacity for directed differentiation into
      a wide variety of neuronal subtypes that may be useful for brain repair. While a
      substantial body of research has lead to a detailed understanding of the ability
      of neurons in fetal tissue grafts to structurally and functionally integrate
      after intra-cerebral transplantation, we are only just beginning to understand
      the in vivo properties of neurons derived from human pluripotent stem cells. Here
      we have utilized the human embryonic stem (ES) cell line Envy, which
      constitutively expresses green fluorescent protein (GFP), in order to study the
      in vivo properties of neurons derived from human ES cells. Rapid and efficient
      neural induction, followed by differentiation as neurospheres resulted in a GFP+
      neural precursor population with traits of neuroepithelial and dorsal forebrain
      identity. Ten weeks after transplantation into neonatal rats, GFP+ fiber patterns
      revealed extensive axonal growth in the host brain, particularly along host white
      matter tracts, although innervation of adjacent nuclei was limited. The grafts
      were composed of a mix of neural cell types including differentiated neurons and
      glia, but also dividing neural progenitors and migrating neuroblasts, indicating
      an incomplete state of maturation at 10 weeks. This was reflected in patch-clamp
      recordings showing stereotypical properties appropriate for mature functional
      neurons, including the ability to generate action potentials, as well profiles
      consistent for more immature neurons. These findings illustrate the intrinsic
      capacity for neurons derived from human ES cells to integrate at a structural and
      functional level following transplantation.

PMID- 22470320
TI  - Connectivity concordance mapping: a new tool for model-free analysis of FMRI data
      of the human brain.
AB  - Functional magnetic resonance data acquired in a task-absent condition ("resting
      state") require new data analysis techniques that do not depend on an activation
      model. Here, we propose a new analysis method called Connectivity Concordance
      Mapping (CCM). The main idea is to assign a label to each voxel based on the
      reproducibility of its whole-brain pattern of connectivity. Specifically, we
      compute the correlations of time courses of each voxel with every other voxel for
      each measurement. Voxels whose correlation pattern is consistent across
      measurements receive high values. The result of a CCM analysis is thus a voxel
      wise map of concordance values. Regions of high inter-subject concordance can be
      assumed to be functionally consistent, and may thus be of specific interest for
      further analysis. Here we present two fMRI studies to demonstrate the possible
      applications of the algorithm. The first is a eyes-open/eyes-closed paradigm
      designed to highlight the potential of the method in a relatively simple domain.
      The second study is a longitudinal repeated measurement of a patient following
      stroke. Longitudinal clinical studies such as this may represent the most
      interesting domain of applications for this algorithm.

PMID- 22470321
TI  - Novel chalcone-based fluorescent human histamine h(3) receptor ligands as
      pharmacological tools.
AB  - Novel fluorescent chalcone-based ligands at human histamine H(3) receptors
      (hH(3)R) have been designed, synthesized, and characterized. Compounds described
      are non-imidazole analogs of ciproxifan with a tetralone motif. Tetralones as
      chemical precursors and related fluorescent chalcones exhibit affinities at
      hH(3)R in the same concentration range like the reference antagonist ciproxifan
      (hH(3)R pK(i) value of 7.2). Fluorescence characterization of our novel ligands
      shows emission maxima about 570 nm for yellow fluorescent chalcones and >=600 nm
      for the red fluorescent derivatives. Interferences to cellular autofluorescence
      could be excluded. All synthesized chalcone compounds could be used to visualize
      hH(3)R proteins in stably transfected HEK-293 cells using confocal laser scanning
      fluorescence microscopy. These novel fluorescent ligands possess high potential
      to be used as pharmacological tools for hH(3)R visualization in different
      tissues.

PMID- 22470322
TI  - Structural changes of the corpus callosum in tinnitus.
AB  - OBJECTIVES: In tinnitus, several brain regions seem to be structurally altered,
      including the medial partition of Heschl's gyrus (mHG), the site of the primary
      auditory cortex. The mHG is smaller in tinnitus patients than in healthy
      controls. The corpus callosum (CC) is the main interhemispheric commissure of the
      brain connecting the auditory areas of the left and the right hemisphere. Here,
      we investigate whether tinnitus status is associated with CC volume. METHODS: The
      midsagittal cross-sectional area of the CC was examined in tinnitus patients and
      healthy controls in which an examination of the mHG had been carried out earlier.
      The CC was extracted and segmented into subregions which were defined according
      to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer
      and Frahm (2006). RESULTS: For both CC segmentation schemes, the CC posterior
      midbody was smaller in male patients than in male healthy controls and the
      isthmus, the anterior midbody, and the genou were larger in female patients than
      in female controls. With CC size normalized relative to mHG volume, the
      normalized CC splenium was larger in male patients than male controls and the
      normalized CC splenium, the isthmus and the genou were larger in female patients
      than female controls. Normalized CC segment size expresses callosal
      interconnectivity relative to auditory cortex volume. CONCLUSION: It may be
      argued that the predominant function of the CC is excitatory. The stronger
      callosal interconnectivity in tinnitus patients, compared to healthy controls,
      may facilitate the emergence and maintenance of a positive feedback loop between
      tinnitus generators located in the two hemispheres.

PMID- 22470323
TI  - Perception of duration in the parvocellular system.
AB  - Both theoretical and experimental evidence suggests that duration perception is
      mediated preferentially by the color-blind but high temporally sensitive
      luminance pathway. In this experiment we tested whether color modulated stimuli
      and high spatial frequency luminance modulated stimuli, which are known to be
      relayed mostly by the slow parvocellular system, are able to elicit reliable
      sense of duration. We show that ramped color modulated stimuli seem to last less
      than luminance modulated stimuli matched for visibility. The effect is large,
      about 200 ms and is constant at all durations tested (range 500-1100 ms).
      However, high spatial frequency luminance stimuli obtain duration matches similar
      to those of low spatial frequency luminance modulated stimuli. The results at
      various levels of contrast and temporal smoothing indicate that equiluminant
      stimuli have higher contrast thresholds to activate the mechanisms which time
      visual stimuli. Overall the results imply that both the magnocellular and the
      parvocellular systems access reliably the timing mechanisms with a difference
      only in the way these are engaged.

PMID- 22470324
TI  - Emotional arousal and multiple memory systems in the mammalian brain.
AB  - Emotional arousal induced by stress and/or anxiety can exert complex effects on
      learning and memory processes in mammals. Recent studies have begun to link study
      of the influence of emotional arousal on memory with earlier research indicating
      that memory is organized in multiple systems in the brain that differ in terms of
      the "type" of memory they mediate. Specifically, these studies have examined
      whether emotional arousal may have a differential effect on the "cognitive" and
      stimulus-response "habit" memory processes sub-served by the hippocampus and
      dorsal striatum, respectively. Evidence indicates that stress or the peripheral
      injection of anxiogenic drugs can bias animals and humans toward the use of
      striatal-dependent habit memory in dual-solution tasks in which both hippocampal
      and striatal-based strategies can provide an adequate solution. A bias toward the
      use of habit memory can also be produced by intra-basolateral amygdala (BLA)
      administration of anxiogenic drugs, consistent with the well documented role of
      efferent projections of this brain region in mediating the modulatory influence
      of emotional arousal on memory. In some learning situations, the bias toward the
      use of habit memory produced by emotional arousal appears to result from an
      impairing effect on hippocampus-dependent cognitive memory. Further research
      examining the neural mechanisms linking emotion and the relative use of multiple
      memory systems should prove useful in view of the potential role for maladaptive
      habitual behaviors in various human psychopathologies.

PMID- 22470325
TI  - Plasticity of Executive Control through Task Switching Training in Adolescents.
AB  - Research has shown that cognitive training can enhance performance in executive
      control tasks. The current study was designed to explore if executive control,
      specifically task switching, can be trained in adolescents, what particular
      aspects of executive control may underlie training and transfer effects, and if
      acute bouts of exercise directly prior to cognitive training enhance training
      effects. For that purpose, a task switching training was employed that has been
      shown to be effective in other age groups. A group of adolescents (10-14 years, n
      = 20) that received a three-session task switching training was compared to a
      group (n = 20) that received the same task switching training but who exercised
      on a stationary bike before each training session. Additionally, a no-contact and
      an exercise only control group were included (both ns = 20). Analyses indicated
      that both training groups significantly reduced their switching costs over the
      course of the training sessions for reaction times and error rates, respectively.
      Analyses indicated transfer to mixing costs in a task switching task that was
      similar to the one used in training. Far transfer was limited to a choice
      reaction time task and a tendency for faster reaction times in an updating task.
      Analyses revealed no additional effects of the exercise intervention. Findings
      thus indicate that executive control can be enhanced in adolescents through
      training and that updating may be of particular relevance for the effects of task
      switching training.

PMID- 22470326
TI  - Pregabalin effects on neural response to emotional faces.
AB  - Pregabalin has shown promise in the treatment of anxiety disorders. Previous
      functional magnetic resonance imaging (fMRI) studies indicate agents used to
      treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and
      medial prefrontal cortex (mPFC) activation during emotional processing. Our prior
      study has shown that during anticipation of an emotional stimulus, pregabalin
      attenuates amygdala and insula activation but increases medial PFC activation. In
      this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin
      attenuates amygdala, insula, and medial PFC during emotional face processing.
      Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study
      investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural
      activation during an emotional face-matching task. Linear mixed model analysis
      revealed that pregabalin dose-dependently attenuated left amygdala activation
      during fearful face-matching and left anterior insula activation during angry
      face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose
      in the right anterior insula and ventral ACC. Thus, pregabalin shares some
      similarity to SSRIs and benzodiazepines in attenuating anger and fear-related
      insula and amygdala activation during emotional face processing. However, there
      is evidence that a subclinical 50 mg dose of pregabalin produced more robust and
      widespread effects on neural responses in this paradigm than the more clinically
      relevant 200 mg dose. Taken together, pregabalin has a slightly different effect
      on brain activation as it relates to anticipation and emotional face processing,
      which may account for its unique characteristic as an agent for the treatment of
      anxiety disorders.

PMID- 22470327
TI  - Time course of information processing in visual and haptic object classification.
AB  - Vision identifies objects rapidly and efficiently. In contrast, object
      recognition by touch is much slower. Furthermore, haptics usually serially
      accumulates information from different parts of objects, whereas vision typically
      processes object information in parallel. Is haptic object identification slower
      simply due to sequential information acquisition and the resulting memory load or
      due to more fundamental processing differences between the senses? To compare the
      time course of visual and haptic object recognition, we slowed visual processing
      using a novel, restricted viewing technique. In an electroencephalographic (EEG)
      experiment, participants discriminated familiar, nameable from unfamiliar,
      unnamable objects both visually and haptically. Analyses focused on the evoked
      and total fronto-central theta-band (5-7 Hz; a marker of working memory) and the
      occipital upper alpha-band (10-12 Hz; a marker of perceptual processing) locked
      to the onset of classification. Decreases in total upper alpha-band activity for
      haptic identification of objects indicate a likely processing role of
      multisensory extrastriate areas. Long-latency modulations of alpha-band activity
      differentiated between familiar and unfamiliar objects in haptics but not in
      vision. In contrast, theta-band activity showed a general increase over time for
      the slowed-down visual recognition task only. We conclude that haptic object
      recognition relies on common representations with vision but also that there are
      fundamental differences between the senses that do not merely arise from
      differences in their speed of processing.

PMID- 22470328
TI  - Do we care about the powerless third? An ERP study of the three-person ultimatum
      game.
AB  - Recent years have provided increasing insights into the factors affecting
      economic decision-making. Little is known about how these factors influence
      decisions that also bear consequences for other people. We examined whether
      decisions that also affected a third, passive player modulate the behavioral and
      neural responses to monetary offers in a modified version of the three-person
      ultimatum game. We aimed to elucidate to what extent social preferences affect
      early neuronal processing when subjects were evaluating offers that were fair or
      unfair to themselves, to the third player, or to both. As an event-related
      potential (ERP) index for early evaluation processes in economic decision-making,
      we recorded the medial frontal negativity (MFN) component in response to such
      offers. Unfair offers were rejected more often than equitable ones, in particular
      when negatively affecting the subject. While the MFN amplitude was higher
      following unfair as compared to fair offers to the subject, MFN amplitude was not
      modulated by the shares assigned to the third, passive player. Furthermore,
      rejection rates and MFN amplitudes following fair offers were positively
      correlated, as subjects showing lower MFN amplitudes following fair offers tended
      to reject unfair offers more often-but only if those offers negatively affected
      their own payoff. Altogether, the rejection behavior suggests that humans mainly
      care about a powerless third when they are confronted with inequality as well.
      The correlation between rejection rates and the MFN amplitude supports the notion
      that this ERP component is also modulated by positive events and highlights how
      our expectations concerning other humans' behavior guide our own decisions.
      However, social preferences like inequality aversion and concern for the well
      being of others are not reflected in this early neuronal response, but seem to
      result from later, deliberate and higher-order cognitive processes.

PMID- 22470329
TI  - Executive control over unconscious cognition: attentional sensitization of
      unconscious information processing.
AB  - Unconscious priming is a prototypical example of an automatic process, which is
      initiated without deliberate intention. Classical theories of automaticity assume
      that such unconscious automatic processes occur in a purely bottom-up driven
      fashion independent of executive control mechanisms. In contrast to these
      classical theories, our attentional sensitization model of unconscious
      information processing proposes that unconscious processing is susceptible to
      executive control and is only elicited if the cognitive system is configured
      accordingly. It is assumed that unconscious processing depends on attentional
      amplification of task-congruent processing pathways as a function of task sets.
      This article provides an overview of the latest research on executive control
      influences on unconscious information processing. I introduce refined theories of
      automaticity with a particular focus on the attentional sensitization model of
      unconscious cognition which is specifically developed to account for various
      attentional influences on different types of unconscious information processing.
      In support of the attentional sensitization model, empirical evidence is reviewed
      demonstrating executive control influences on unconscious cognition in the
      domains of visuo-motor and semantic processing: subliminal priming depends on
      attentional resources, is susceptible to stimulus expectations and is influenced
      by action intentions and task sets. This suggests that even unconscious
      processing is flexible and context-dependent as a function of higher-level
      executive control settings. I discuss that the assumption of attentional
      sensitization of unconscious information processing can accommodate conflicting
      findings regarding the automaticity of processes in many areas of cognition and
      emotion. This theoretical view has the potential to stimulate future research on
      executive control of unconscious processing in healthy and clinical populations.

PMID- 22470330
TI  - Working-memory training in younger and older adults: training gains, transfer,
      and maintenance.
AB  - Working memory (WM), a key determinant of many higher-order cognitive functions,
      declines in old age. Current research attempts to develop process-specific WM
      training procedures, which may lead to general cognitive improvement. Adaptivity
      of the training as well as the comparison of training gains to performance
      changes of an active control group are key factors in evaluating the
      effectiveness of a specific training program. In the present study, 55 younger
      adults (20-30 years of age) and 45 older adults (60-70 years of age) received 5
      weeks of computerized training on various spatial and verbal WM tasks. Half of
      the sample received adaptive training (i.e., individually adjusted task
      difficulty), whereas the other half-worked on the same task material but on a low
      task difficulty level (active controls). Performance was assessed using
      criterion, near-transfer, and far-transfer tasks before training, after 5 weeks
      of intervention, as well as after a 3-month follow-up interval. Results indicate
      that (a) adaptive training generally led to larger training gains than low-level
      practice, (b) training and transfer gains were somewhat greater for younger than
      for older adults in some tasks, but comparable across age groups in other tasks,
      (c) far-transfer was observed to a test on sustained attention and for a self
      rating scale on cognitive functioning in daily life for both young and old, and
      (d) training gains and transfer effects were maintained across the 3-month follow
      up interval across age.

PMID- 22470331
TI  - Age-related dissociation of sensory and decision-based auditory motion
      processing.
AB  - Studies on the maturation of auditory motion processing in children have yielded
      inconsistent reports. The present study combines subjective and objective
      measurements to investigate how the auditory perceptual abilities of children
      change during development and whether these changes are paralleled by changes in
      the event-related brain potential (ERP). We employed the mismatch negativity
      (MMN) to determine maturational changes in the discrimination of interaural time
      differences (ITDs) that generate lateralized moving auditory percepts. MMNs were
      elicited in children, teenagers, and adults, using a small and a large ITD at
      stimulus offset with respect to each subject's discrimination threshold. In
      adults and teenagers large deviants elicited prominent MMNs, whereas small
      deviants at the behavioral threshold elicited only a marginal or no MMN. In
      contrast, pronounced MMNs for both deviant sizes were found in children.
      Behaviorally, however, most of the children showed higher discrimination
      thresholds than teens and adults. Although automatic ITD detection is functional,
      active discrimination is still limited in children. The lack of MMN deviance
      dependency in children suggests that unlike in teenagers and adults, neural
      signatures of automatic auditory motion processing do not mirror discrimination
      abilities. The study critically accounts for advanced understanding of children's
      central auditory development.

PMID- 22470332
TI  - An electrophysiological signal that precisely tracks the emergence of error
      awareness.
AB  - Recent electrophysiological research has sought to elucidate the neural
      mechanisms necessary for the conscious awareness of action errors. Much of this
      work has focused on the error positivity (Pe), a neural signal that is
      specifically elicited by errors that have been consciously perceived. While
      awareness appears to be an essential prerequisite for eliciting the Pe, the
      precise functional role of this component has not been identified. Twenty-nine
      participants performed a novel variant of the Go/No-go Error Awareness Task (EAT)
      in which awareness of commission errors was indicated via a separate speeded
      manual response. Independent component analysis (ICA) was used to isolate the Pe
      from other stimulus- and response-evoked signals. Single-trial analysis revealed
      that Pe peak latency was highly correlated with the latency at which awareness
      was indicated. Furthermore, the Pe was more closely related to the timing of
      awareness than it was to the initial erroneous response. This finding was
      confirmed in a separate study which derived IC weights from a control condition
      in which no indication of awareness was required, thus ruling out motor
      confounds. A receiver-operating-characteristic (ROC) curve analysis showed that
      the Pe could reliably predict whether an error would be consciously perceived up
      to 400 ms before the average awareness response. Finally, Pe latency and
      amplitude were found to be significantly correlated with overall error awareness
      levels between subjects. Our data show for the first time that the temporal
      dynamics of the Pe trace the emergence of error awareness. These findings have
      important implications for interpreting the results of clinical EEG studies of
      error processing.

PMID- 22470333
TI  - The hippocampus and inferential reasoning: building memories to navigate future
      decisions.
AB  - A critical aspect of inferential reasoning is the ability to form relationships
      between items or events that were not experienced together. This review considers
      different perspectives on the role of the hippocampus in successful inferential
      reasoning during both memory encoding and retrieval. Intuitively, inference can
      be thought of as a logical process by which elements of individual existing
      memories are retrieved and recombined to answer novel questions. Such flexible
      retrieval is sub-served by the hippocampus and is thought to require specialized
      hippocampal encoding mechanisms that discretely code events such that event
      elements are individually accessible from memory. In addition to retrieval-based
      inference, recent research has also focused on hippocampal processes that support
      the combination of information acquired across multiple experiences during
      encoding. This mechanism suggests that by recalling past events during new
      experiences, connections can be created between newly formed and existing
      memories. Such hippocampally mediated memory integration would thus underlie the
      formation of networks of related memories that extend beyond direct experience to
      anticipate future judgments about the relationships between items and events. We
      also discuss integrative encoding in the context of emerging evidence linking the
      hippocampus to the formation of schemas as well as prospective theories of
      hippocampal function that suggest memories are actively constructed to anticipate
      future decisions and actions.

PMID- 22470334
TI  - Functional Differences between Global Pre- and Postsynaptic Inhibition in the
      Drosophila Olfactory Circuit.
AB  - The Drosophila antennal lobe is subdivided into multiple glomeruli, each of which
      represents a unique olfactory information processing channel. In each glomerulus,
      feedforward input from olfactory receptor neurons (ORNs) is transformed into
      activity of projection neurons (PNs), which represent the output. Recent
      investigations have indicated that lateral presynaptic inhibitory input from
      other glomeruli controls the gain of this transformation. Here, we address why
      this gain control acts "pre"-synaptically rather than "post"-synaptically.
      Postsynaptic inhibition could work similarly to presynaptic inhibition with
      regard to regulating the firing rates of PNs depending on the stimulus intensity.
      We investigate the differences between pre- and postsynaptic gain control in
      terms of odor discriminability by simulating a network model of the Drosophila
      antennal lobe with experimental data. We first demonstrate that only presynaptic
      inhibition can reproduce the type of gain control observed in experiments. We
      next show that presynaptic inhibition decorrelates PN responses whereas
      postsynaptic inhibition does not. Due to this effect, presynaptic gain control
      enhances the accuracy of odor discrimination by a linear decoder while its
      postsynaptic counterpart only diminishes it. Our results provide the reason gain
      control operates "pre"-synaptically but not "post"-synaptically in the Drosophila
      antennal lobe.

PMID- 22470335
TI  - Wanted dead or alive? The tradeoff between in-vivo versus ex-vivo MR brain
      imaging in the mouse.
AB  - High-resolution MRI of the mouse brain is gaining prominence in estimating
      changes in neuroanatomy over time to understand both normal developmental as well
      as disease processes and mechanisms. These types of experiments, where a change
      in time is to be captured as accurately as possible using imaging, face multiple
      experimental design choices. Chief amongst these choices is whether to image ex
      vivo, where superior resolution and contrast are available, or in-vivo, where
      resolution and contrast are lower but the animal can be followed longitudinally.
      Here we explore this tradeoff by first estimating the sources of variability in
      anatomical mouse MRI and then, using statistical simulations, provide power
      analyses of these experiment design choices.

PMID- 22470336
TI  - Practical management of heterogeneous neuroimaging metadata by global
      neuroimaging data repositories.
AB  - Rapidly evolving neuroimaging techniques are producing unprecedented quantities
      of digital data at the same time that many research studies are evolving into
      global, multi-disciplinary collaborations between geographically distributed
      scientists. While networked computers have made it almost trivial to transmit
      data across long distances, collecting and analyzing this data requires extensive
      metadata if the data is to be maximally shared. Though it is typically
      straightforward to encode text and numerical values into files and send content
      between different locations, it is often difficult to attach context and implicit
      assumptions to the content. As the number of and geographic separation between
      data contributors grows to national and global scales, the heterogeneity of the
      collected metadata increases and conformance to a single standardization becomes
      implausible. Neuroimaging data repositories must then not only accumulate data
      but must also consolidate disparate metadata into an integrated view. In this
      article, using specific examples from our experiences, we demonstrate how
      standardization alone cannot achieve full integration of neuroimaging data from
      multiple heterogeneous sources and why a fundamental change in the architecture
      of neuroimaging data repositories is needed instead.

PMID- 22470337
TI  - Correspondence between structure and function in the human brain at rest.
AB  - To further understanding of basic and complex cognitive functions, previous
      connectome research has identified functional and structural connections of the
      human brain. Functional connectivity is often measured by using resting-state
      functional magnetic resonance imaging (rs-fMRI) and is generally interpreted as
      an indirect measure of neuronal activity. Gray matter (GM) primarily consists of
      neuronal and glia cell bodies; therefore, it is surprising that the majority of
      connectome research has excluded GM measures. Therefore, we propose that by
      exploring where GM corresponds to function would aid in the understanding of both
      structural and functional connectivity and in turn the human connectome. A cohort
      of 603 healthy participants underwent structural and functional scanning on the
      same 3 T scanner at the Mind Research Network. To investigate the spatial
      correspondence between structure and function, spatial independent component
      analysis (ICA) was applied separately to both GM density (GMD) maps and to rs
      fMRI data. ICA of GM delineates structural components based on the covariation of
      GMD regions among subjects. For the rs-fMRI data, ICA identified spatial patterns
      with common temporal features. These decomposed structural and functional
      components were then compared by spatial correlation. Basal ganglia components
      exhibited the highest structural to resting-state functional spatial correlation
      (r = 0.59). Cortical components generally show correspondence between a single
      structural component and several resting-state functional components. We also
      studied relationships between the weights of different structural components and
      identified the precuneus as a hub in GMD structural network correlations. In
      addition, we analyzed relationships between component weights, age, and gender;
      concluding that age has a significant effect on structural components.

PMID- 22470338
TI  - The language-number interface in the brain: a complex parametric study of
      quantifiers and quantities.
AB  - The neural bases for numerosity and language are of perennial interest. In
      monkeys, neural separation of numerical Estimation and numerical Comparison has
      been demonstrated. As linguistic and numerical knowledge can only be compared in
      humans, we used a new fMRI paradigm in an attempt to dissociate Estimation from
      Comparison, and at the same time uncover the neural relation between numerosity
      and language. We used complex stimuli: images depicting a proportion between
      quantities of blue and yellow circles were coupled with sentences containing
      quantifiers that described them (e.g., "most/few of the circles are yellow").
      Participants verified sentences against images. Both Estimation and Comparison
      recruited adjacent, partially overlapping bi-hemispheric fronto-parietal regions.
      Additional semantic analysis of positive vs. negative quantifiers involving the
      interpretation of quantity and numerosity specifically recruited left area 45.
      The anatomical proximity between numerosity regions and those involved in
      semantic analysis points to subtle links between the number system and language.
      Results fortify the homology of Estimation and Comparison between humans and
      monkeys.

PMID- 22470339
TI  - Interactomic and pharmacological insights on human sirt-1.
AB  - Sirt-1 is defined as a nuclear protein involved in the molecular mechanisms of
      inflammation and neurodegeneration through the de-acetylation of many different
      substrates even if experimental data in mouse suggest both its cytoplasmatic
      presence and nucleo-cytoplasmic shuttling upon oxidative stress. Since the
      experimental structure of human Sirt-1 has not yet been reported, we have modeled
      its 3D structure, highlighted that it is composed by four different structural
      regions: N-terminal region, allosteric site, catalytic core and C-terminal
      region, and underlined that the two terminal regions have high intrinsic disorder
      propensity and numerous putative phosphorylation sites. Many different papers
      report experimental studies related to its functional activators because Sirt-1
      is implicated in various diseases and cancers. The aim of this article is (i) to
      present interactomic studies based human Sirt-1 to understand its most important
      functional relationships in the light of the gene-protein interactions that
      control major metabolic pathways and (ii) to show by docking studies how this
      protein binds some activator molecules in order to evidence structural
      determinants, physico-chemical features and those residues involved in the
      formation of complexes.

PMID- 22470341
TI  - Bilirubin inhibits neointima formation and vascular smooth muscle cell
      proliferation and migration.
AB  - Bilirubin is a heme metabolite generated by the concerted action of the enzymes
      heme oxygenase and biliverdin reductase. Although long considered a toxic
      byproduct of heme catabolism, recent preclinical, and clinical studies indicate
      the bilirubin exerts beneficial effects in the circulation. In the present study,
      we determined whether local administration of bilirubin attenuates neointima
      formation following injury of rat carotid arteries. In addition, the ability of
      bilirubin to regulate the proliferation and migration of human arterial smooth
      muscle cells (SMCs) was investigated. Local perivascular administration of
      bilirubin immediately following balloon injury of rat carotid arteries
      significantly attenuated neointima formation. Bilirubin-mediated inhibition of
      neointimal thickening was associated with a significant decrease in ERK activity
      and cyclin D1 and A protein expression, and an increase in p21 and p53 protein
      expression in injured blood vessels. Treatment of human aortic SMCs with
      bilirubin inhibited proliferation and migration in a concentration-dependent
      manner without affecting cell viability. In addition, bilirubin resulted in a
      concentration-dependent increase in the percentage of cells in the G(0)/G(1)
      phase of the cell cycle and this was paralleled by a decrease in the fraction of
      cells in the S and G(2)M phases of the cell cycle. Finally, bilirubin had no
      effect on mitochondrial function and ATP content of vascular SMCs. In conclusion,
      these studies demonstrate that bilirubin inhibits neointima formation after
      arterial injury and this is associated with alterations in the expression of cell
      cycle regulatory proteins. Furthermore, bilirubin blocks proliferation and
      migration of human arterial SMCs and arrests SMCs in the G(0)/G(1) phase of the
      cell cycle. Bilirubin represents an attractive therapeutic agent in treating
      occlusive vascular disease.

PMID- 22470340
TI  - Cellular Links between Neuronal Activity and Energy Homeostasis.
AB  - Neuronal activity, astrocytic responses to this activity, and energy homeostasis
      are linked together during baseline, conscious conditions, and short-term rapid
      activation (as occurs with sensory or motor function). Nervous system energy
      homeostasis also varies during long-term physiological conditions (i.e.,
      development and aging) and with adaptation to pathological conditions, such as
      ischemia or low glucose. Neuronal activation requires increased metabolism (i.e.,
      ATP generation) which leads initially to substrate depletion, induction of a
      variety of signals for enhanced astrocytic function, and increased local blood
      flow and substrate delivery. Energy generation (particularly in mitochondria) and
      use during ATP hydrolysis also lead to considerable heat generation. The local
      increases in blood flow noted following neuronal activation can both enhance
      local substrate delivery but also provides a heat sink to help cool the brain and
      removal of waste by-products. In this review we highlight the interactions
      between short-term neuronal activity and energy metabolism with an emphasis on
      signals and factors regulating astrocyte function and substrate supply.

PMID- 22470343
TI  - Ganoderma lucidum and Professor Zhi-Bin Lin.

PMID- 22470344
TI  - Restraint Stress Intensifies Interstitial K(+) Accumulation during Severe
      Hypoxia.
AB  - Chronic stress affects neuronal networks by inducing dendritic retraction,
      modifying neuronal excitability and plasticity, and modulating glial cells. To
      elucidate the functional consequences of chronic stress for the hippocampal
      network, we submitted adult rats to daily restraint stress for 3 weeks (6 h/day).
      In acute hippocampal tissue slices of stressed rats, basal synaptic function and
      short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged
      while long-term potentiation was markedly impaired. The spatiotemporal
      propagation pattern of hypoxia-induced spreading depression episodes was
      indistinguishable among control and stress slices. However, the duration of the
      extracellular direct current potential shift was shortened after stress.
      Moreover, K(+) fluxes early during hypoxia were more intense, and the
      postsynaptic recoveries of interstitial K(+) levels and synaptic function were
      slower. Morphometric analysis of immunohistochemically stained sections suggested
      hippocampal shrinkage in stressed rats, and the number of cells that are
      immunoreactive for glial fibrillary acidic protein was increased in the CA1
      subfield indicating activation of astrocytes. Western blots showed a marked
      downregulation of the inwardly rectifying K(+) channel Kir4.1 in stressed rats.
      Yet, resting membrane potentials, input resistance, and K(+)-induced inward
      currents in CA1 astrocytes were indistinguishable from controls. These data
      indicate an intensified interstitial K(+) accumulation during hypoxia in the
      hippocampus of chronically stressed rats which seems to arise from a reduced
      interstitial volume fraction rather than impaired glial K(+) buffering. One may
      speculate that chronic stress aggravates hypoxia-induced pathophysiological
      processes in the hippocampal network and that this has implications for the
      ischemic brain.

PMID- 22470345
TI  - The Splicing Factor SRSF1 as a Marker for Endothelial Senescence.
AB  - Aging is the major risk factor per se for the development of cardiovascular
      diseases. The senescence of the endothelial cells (ECs) that line the lumen of
      blood vessels is the cellular basis for these age-dependent vascular pathologies,
      including atherosclerosis and hypertension. During their lifespan, ECs may reach
      a stage of senescence by two different pathways; a replicative one derived from
      their preprogrammed finite number of cell divisions; and one induced by stress
      stimuli. Also, certain physiological stimuli, such as transforming growth factor
      beta, are able to modulate cellular senescence. Currently, the cellular aging
      process is being widely studied to identify novel molecular markers whose changes
      correlate with senescence. This review focuses on the regulation of alternative
      splicing mediated by the serine-arginine splicing factor 1 (SRSF1, or ASF/SF2)
      during endothelial senescence, a process that is associated with a differential
      subcellular localization of SRSF1, which typically exhibits a scattered
      distribution throughout the cytoplasm. Based on its senescence-dependent
      involvement in alternative splicing, we postulate that SRSF1 is a key marker of
      EC senescence, regulating the expression of alternative isoforms of target genes
      such as endoglin (ENG), vascular endothelial growth factor A (VEGFA), tissue
      factor (T3), or lamin A (LMNA) that integrate in a common molecular senescence
      program.

PMID- 22470342
TI  - Cytoplasmic domains and voltage-dependent potassium channel gating.
AB  - The basic architecture of the voltage-dependent K(+) channels (Kv channels)
      corresponds to a transmembrane protein core in which the permeation pore, the
      voltage-sensing components and the gating machinery (cytoplasmic facing gate and
      sensor-gate coupler) reside. Usually, large protein tails are attached to this
      core, hanging toward the inside of the cell. These cytoplasmic regions are
      essential for normal channel function and, due to their accessibility to the
      cytoplasmic environment, constitute obvious targets for cell-physiological
      control of channel behavior. Here we review the present knowledge about the
      molecular organization of these intracellular channel regions and their role in
      both setting and controlling Kv voltage-dependent gating properties. This
      includes the influence that they exert on Kv rapid/N-type inactivation and on
      activation/deactivation gating of Shaker-like and eag-type Kv channels. Some
      illustrative examples about the relevance of these cytoplasmic domains
      determining the possibilities for modulation of Kv channel gating by cellular
      components are also considered.

PMID- 22470346
TI  - Protein kinase d regulates cell death pathways in experimental pancreatitis.
AB  - Inflammation and acinar cell necrosis are two major pathological responses of
      acute pancreatitis, a serious disorder with no current therapies directed to its
      molecular pathogenesis. Serine/threonine protein kinase D family, which includes
      PKD/PKD1, PKD2, and PKD3, has been increasingly implicated in the regulation of
      multiple physiological and pathophysiological effects. We recently reported that
      PKD/PKD1, the predominant PKD isoform expressed in rat pancreatic acinar cells,
      mediates early events of pancreatitis including NF-kappaB activation and
      inappropriate intracellular digestive enzyme activation. In current studies, we
      investigated the role and mechanisms of PKD/PKD1 in the regulation of necrosis in
      pancreatic acinar cells by using two novel small molecule PKD inhibitors
      CID755673 and CRT0066101 and molecular approaches in in vitro and in vivo
      experimental models of acute pancreatitis. Our results demonstrated that both
      CID755673 and CRT0066101 are PKD-specific inhibitors and that PKD/PKD1 inhibition
      by either the chemical inhibitors or specific PKD/PKD1 siRNAs attenuated necrosis
      while promoting apoptosis induced by pathological doses of cholecystokinin
      octapeptide (CCK) in pancreatic acinar cells. Conversely, up-regulation of PKD
      expression in pancreatic acinar cells increased necrosis and decreased apoptosis.
      We further showed that PKD/PKD1 regulated several key cell death signals
      including inhibitors of apoptotic proteins, caspases, receptor-interacting
      protein kinase 1 to promote necrosis. PKD/PKD1 inhibition by CID755673
      significantly ameliorated necrosis and severity of pancreatitis in an in vivo
      experimental model of acute pancreatitis. Thus, our studies indicate that
      PKD/PKD1 is a key mediator of necrosis in acute pancreatitis and that PKD/PKD1
      may represent a potential therapeutic target in acute pancreatitis.

PMID- 22470347
TI  - Activity-dependent neuronal model on complex networks.
AB  - Neuronal avalanches are a novel mode of activity in neuronal networks,
      experimentally found in vitro and in vivo, and exhibit a robust critical
      behavior: these avalanches are characterized by a power law distribution for the
      size and duration, features found in other problems in the context of the physics
      of complex systems. We present a recent model inspired in self-organized
      criticality, which consists of an electrical network with threshold firing,
      refractory period, and activity-dependent synaptic plasticity. The model
      reproduces the critical behavior of the distribution of avalanche sizes and
      durations measured experimentally. Moreover, the power spectra of the electrical
      signal reproduce very robustly the power law behavior found in human
      electroencephalogram (EEG) spectra. We implement this model on a variety of
      complex networks, i.e., regular, small-world, and scale-free and verify the
      robustness of the critical behavior.

PMID- 22470349
TI  - Modulation of La Crosse Virus Infection in Aedes albopictus Mosquitoes Following
      Larval Exposure to Coffee Extracts.
AB  - The mosquito-borne La Crosse virus (LACV; Family Bunyaviridae) may cause
      encephalitis, primarily in children, and is distributed throughout much of the
      eastern United States. No antivirals or vaccines are available for LACV, or most
      other mosquito-borne viruses, and prevention generally relies on mosquito
      control. We sought to determine whether coffee extracts could interfere with LACV
      replication and vector mosquito development. Both regular and decaffeinated
      coffee demonstrated significant reductions in LACV replication in direct
      antiviral assays. This activity was not due to the presence of caffeine, which
      did not inhibit the virus life cycle. Aedes albopictus (Skuse; Diptera:
      Culicidae) mosquito larvae suffered near total mortality when reared in high
      concentrations of regular and decaffeinated coffee and in caffeine. Following
      larval exposure to sublethal coffee concentrations, adult A. albopictus
      mosquitoes had significantly reduced whole-body LACV titers 5 days post
      infection, compared to larvae reared in distilled water. These results suggest
      that it may be possible to both control mosquito populations and alter the vector
      competence of mosquitoes for arthropod-borne viruses by introducing antiviral
      compounds into the larval habitat.

PMID- 22470348
TI  - Impact of climate trends on tick-borne pathogen transmission.
AB  - Recent advances in climate research together with a better understanding of tick
      pathogen interactions, the distribution of ticks and the diagnosis of tick-borne
      pathogens raise questions about the impact of environmental factors on tick
      abundance and spread and the prevalence and transmission of tick-borne pathogens.
      While undoubtedly climate plays a role in the changes in distribution and
      seasonal abundance of ticks, it is always difficult to disentangle factors
      impacting on the abundance of tick hosts from those exerted by human habits. All
      together, climate, host abundance, and social factors may explain the upsurge of
      epidemics transmitted by ticks to humans. Herein we focused on tick-borne
      pathogens that affect humans with epidemic potential. Borrelia burgdorferi s.l.
      (Lyme disease), Anaplasma phagocytophilum (human granulocytic anaplasmosis), and
      tick-borne encephalitis virus (tick-borne encephalitis) are transmitted by Ixodes
      spp. Crimean-Congo hemorrhagic fever virus (Crimean-Congo hemorrhagic fever) is
      transmitted by Hyalomma spp. In this review, we discussed how vector tick species
      occupy the habitat as a function of different climatic factors, and how these
      factors impact on tick survival and seasonality. How molecular events at the tick
      pathogen interface impact on pathogen transmission is also discussed. Results
      from statistically and biologically derived models are compared to show that
      while statistical models are able to outline basic information about tick
      distributions, biologically derived models are necessary to evaluate pathogen
      transmission rates and understand the effect of climatic variables and host
      abundance patterns on pathogen transmission. The results of these studies could
      be used to build early alert systems able to identify the main factors driving
      the subtle changes in tick distribution and seasonality and the prevalence of
      tick-borne pathogens.

PMID- 22470350
TI  - New insights into phospholipase d and sphingosine kinase activation in
      Arabidopsis.

PMID- 22470351
TI  - Effect of dietary omega-3 polyunsaturated Fatty acids on heart rate and heart
      rate variability in animals susceptible or resistant to ventricular fibrillation.
AB  - The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been
      reported to reduce cardiac mortality following myocardial infarction as well as
      to decrease resting heart rate (HR) and increase HR variability (HRV). However,
      it has not been established whether n-3 PUFAs exhibit the same actions on HR and
      HRV in individuals known to be either susceptible or resistant to ventricular
      fibrillation (VF). Therefore, HR and HRV (high frequency and total R-R interval
      variability) were evaluated before and 3 months after n-3 PUFA treatment in dogs
      with healed myocardial infarction that were either susceptible (VF+, n = 31) or
      resistant (VF-, n = 31) to ventricular tachyarrhythmias induced by a 2-min
      coronary artery occlusion during the last minute of a submaximal exercise test.
      HR and HRV were evaluated at rest, during submaximal exercise and in response to
      acute myocardial ischemia at rest before and after either placebo (1 g/day, corn
      oil, VF+, n = 9; VF- n = 8) or n-3 PUFA (docosahexaenoic acid + eicosapentaenoic
      acid ethyl esters, 1-4 g/day, VF+, n = 22; VF-, n = 23) treatment for 3 months.
      The n-3 PUFA treatment elicited similar increases in red blood cell membrane,
      right atrial, and left ventricular n-3 PUFA levels in both the VF+ and VF- dogs.
      The n-3 PUFA treatment also provoked similar reductions in baseline HR and
      increases in baseline HRV in both groups that resulted in parallel shifts in the
      response to either exercise or acute myocardial ischemia (that is, the change in
      these variables induced by physiological challenges was not altered after n-3
      PUFA treatment). These data demonstrate that dietary n-3 PUFA decreased HR and
      increased HRV to a similar extent in animals known to be prone to or resistant to
      malignant cardiac tachyarrhythmias.

PMID- 22470352
TI  - Resting state functional connectivity correlates of inhibitory control in
      children with attention-deficit/hyperactivity disorder.
AB  - Motor inhibition is among the most commonly studied executive functions in
      attention-deficit/hyperactivity disorder (ADHD). Imaging studies using probes of
      motor inhibition such as the stop signal task (SST) consistently demonstrate ADHD
      related dysfunction within a right-hemisphere fronto-striatal network that
      includes inferior frontal gyrus and pre-supplementary motor area. Beyond findings
      of focal hypo- or hyper-function, emerging models of ADHD psychopathology
      highlight disease-related changes in functional interactions between network
      components. Resting state fMRI (R-fMRI) approaches have emerged as powerful tools
      for mapping such interactions (i.e., resting state functional connectivity,
      RSFC), and for relating behavioral and diagnostic variables to network
      properties. We used R-fMRI data collected from 17 typically developing controls
      (TDC) and 17 age-matched children with ADHD (aged 8-13 years) to identify neural
      correlates of SST performance measured outside the scanner. We examined two
      related inhibition indices: stop signal reaction time (SSRT), indexing inhibitory
      speed, and stop signal delay (SSD), indexing inhibitory success. Using 11 fronto
      striatal seed regions-of-interest, we queried the brain for relationships between
      RSFC and each performance index, as well as for interactions with diagnostic
      status. Both SSRT and SSD exhibited connectivity-behavior relationships
      independent of diagnosis. At the same time, we found differential connectivity
      behavior relationships in children with ADHD relative to TDC. Our results
      demonstrate the utility of RSFC approaches for assessing brain/behavior
      relationships, and for identifying pathology-related differences in the
      contributions of neural circuits to cognition and behavior.

PMID- 22470353
TI  - Dihydrocodeine/Agonists for alcohol dependents.
AB  - OBJECTIVE: Alcohol addiction too often remains insufficiently treated. It shows
      the same profile as severe chronic diseases, but no comparable, effective basic
      treatment has been established up to now. Especially patients with repeated
      relapses, despite all therapeutic approaches, and patients who are not able to
      attain an essential abstinence to alcohol, need a basic medication. It seems
      necessary to acknowledge that parts of them need any agonistic substance, for
      years, possibly lifelong. For >14 years, we have prescribed such substances with
      own addictive character for these patients. METHODS: We present a documented best
      possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine
      (DHC) to 102 heavily alcohol addicted patients, later, also Buprenorphine,
      Clomethiazole (>6 weeks), Baclofen, and in one case Amphetamine, each on
      individual indication. This paper focuses on the data with DHC, especially. The
      Clomethiazole-data has been submitted to a German journal. The number of
      treatments with the other substances is still low. RESULTS: The 102 patients with
      the DHC treatment had 1367 medically assisted detoxifications and specialized
      therapies before! The 4 years-retention rate was 26.4%, including 2.8%
      successfully terminated treatments. In our 12-steps scale on clinical impression,
      we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The
      demand for medically assisted detoxifications in the 2 years remaining patients
      was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l
      after 2 years. Experiences with the other substances are similar but different in
      details. CONCLUSION: Similar to the Italian studies with GHB and Baclofen, we
      present a new approach, not only with new substances, but also with a new setting
      and much more trusting attitude. We observe a huge improvement, reaching an
      almost optimal, stable, long term status in around 1/4 of the patients already.
      Many further optimizations are possible.

PMID- 22470354
TI  - Serotonin transporter genomic biomarker for quantitative assessment of
      ondansetron treatment response in alcoholics.
AB  - Paucity of sensitive biomarkers to quantify transient changes in alcohol
      consumption level remains a critical barrier for the development of efficacious
      therapeutic agents to treat alcoholism. Recently, in an 11-week, randomized,
      placebo-controlled, double-blind trial of 283 alcohol-dependent individuals, we
      demonstrated that ondansetron was efficacious at reducing the severity of
      drinking (measured as drinks per drinking day; DDD) in alcoholics carrying the LL
      compared with the LS/SS genotype of the serotonin transporter gene, 5'-HTTLPR.
      Using peripheral blood samples from a cohort of 41 of these subjects, we
      determined whether there was a relationship between mRNA expression level of the
      5'-HTTLPR genotypes (measured at weeks 0, 4, and 11) and self-reported alcohol
      consumption following treatment with either ondansetron (4 MUg/kg twice daily; N
      = 19) or placebo (N = 22). Using a mixed-effects linear regression model, we
      analyzed the effects of DDD and 5'-HTTLPR genotypes on mRNA expression levels
      within and between the ondansetron and placebo groups. We found a significant
      three-way interaction effect of DDD, 5'-HTTLPR genotypes, and treatment on mRNA
      expression levels (p = 0.0396). Among ondansetron but not placebo recipients,
      there was a significant interaction between DDD and 5'-HTTLPR genotype (p =
      0.0385 and p = 0.7938, respectively). In the ondansetron group, DDD was
      associated positively with mRNA levels at a greater rate of expression alteration
      per standard drink in those with the LL genotype (slope = +1.1698 in ln scale).
      We suggest that the combination of the LL genotype and 5'-HTTLPR mRNA expression
      levels might be a promising and novel biomarker to quantify drinking severity in
      alcoholics treated with ondansetron.

PMID- 22470356
TI  - By fault or by default.

PMID- 22470355
TI  - X-chromosome inactivation in rett syndrome human induced pluripotent stem cells.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder that affects girls due
      primarily to heterozygous mutations in the X-linked gene encoding methyl-CpG
      binding protein 2 (MECP2). Random X-chromosome inactivation (XCI) results in
      cellular mosaicism in which some cells express wild-type (WT) MECP2 while other
      cells express mutant MECP2. The generation of patient-specific human induced
      pluripotent stem cells (hiPSCs) facilitates the production of RTT-hiPSC-derived
      neurons in vitro to investigate disease mechanisms and identify novel drug
      treatments. The generation of RTT-hiPSCs has been reported by many laboratories,
      however, the XCI status of RTT-hiPSCs has been inconsistent. Some report RTT
      hiPSCs retain the inactive X-chromosome (post-XCI) of the founder somatic cell
      allowing isogenic RTT-hiPSCs that express only the WT or mutant MECP2 allele to
      be isolated from the same patient. Post-XCI RTT-hiPSCs-derived neurons retain
      this allele-specific expression pattern of WT or mutant MECP2. Conversely, others
      report RTT-hiPSCs in which the inactive X-chromosome of the founder somatic cell
      reactivates (pre-XCI) upon reprogramming into RTT-hiPSCs. Pre-XCI RTT-hiPSC
      derived neurons exhibit random XCI resulting in cellular mosaicism with respect
      to WT and mutant MECP2 expression. Here we review and attempt to interpret the
      inconsistencies in XCI status of RTT-hiPSCs generated to date by comparison to
      other pluripotent systems in vitro and in vivo and the methods used to analyze
      XCI. Finally, we discuss the relative strengths and weaknesses of post- and pre
      XCI hiPSCs in the context of RTT, and other X-linked and autosomal disorders for
      translational medicine.

PMID- 22470357
TI  - Are the products of statistical learning abstract or stimulus-specific?
AB  - Learners can segment potential lexical units from syllable streams when
      statistically variable transitional probabilities between adjacent syllables are
      the only cues to word boundaries. Here we examine the nature of the
      representations that result from statistical learning by assessing learners'
      ability to generalize across acoustically different stimuli. In three
      experiments, we compare two possibilities: that the products of statistical
      segmentation processes are abstract and generalizable representations, or,
      alternatively, that products of statistical learning are stimulus-bound and
      restricted to perceptually similar instances. In Experiment 1, learners segmented
      units from statistically predictable streams, and recognized these units when
      they were acoustically transformed by temporal reversals. In Experiment 2,
      learners were able to segment units from temporally reversed syllable streams,
      but were only able to generalize in conditions of mild acoustic transformation.
      In Experiment 3, learners were able to recognize statistically segmented units
      after a voice change but were unable to do so when the novel voice was mildly
      distorted. Together these results suggest that representations that result from
      statistical learning can be abstracted to some degree, but not in all listening
      conditions.

PMID- 22470358
TI  - Use of prosody and information structure in high functioning adults with autism
      in relation to language ability.
AB  - Abnormal prosody is a striking feature of the speech of those with Autism
      spectrum disorder (ASD), but previous reports suggest large variability among
      those with ASD. Here we show that part of this heterogeneity can be explained by
      level of language functioning. We recorded semi-spontaneous but controlled
      conversations in adults with and without ASD and measured features related to
      pitch and duration to determine (1) general use of prosodic features, (2)
      prosodic use in relation to marking information structure, specifically, the
      emphasis of new information in a sentence (focus) as opposed to information
      already given in the conversational context (topic), and (3) the relation between
      prosodic use and level of language functioning. We found that, compared to
      typical adults, those with ASD with high language functioning generally used a
      larger pitch range than controls but did not mark information structure, whereas
      those with moderate language functioning generally used a smaller pitch range
      than controls but marked information structure appropriately to a large extent.
      Both impaired general prosodic use and impaired marking of information structure
      would be expected to seriously impact social communication and thereby lead to
      increased difficulty in personal domains, such as making and keeping friendships,
      and in professional domains, such as competing for employment opportunities.

PMID- 22470359
TI  - Amplitude onsets and spectral energy in perceptual experience.

PMID- 22470360
TI  - A network model of observation and imitation of speech.
AB  - Much evidence has now accumulated demonstrating and quantifying the extent of
      shared regional brain activation for observation and execution of speech.
      However, the nature of the actual networks that implement these functions, i.e.,
      both the brain regions and the connections among them, and the similarities and
      differences across these networks has not been elucidated. The current study aims
      to characterize formally a network for observation and imitation of syllables in
      the healthy adult brain and to compare their structure and effective
      connectivity. Eleven healthy participants observed or imitated audiovisual
      syllables spoken by a human actor. We constructed four structural equation models
      to characterize the networks for observation and imitation in each of the two
      hemispheres. Our results show that the network models for observation and
      imitation comprise the same essential structure but differ in important ways from
      each other (in both hemispheres) based on connectivity. In particular, our
      results show that the connections from posterior superior temporal gyrus and
      sulcus to ventral premotor, ventral premotor to dorsal premotor, and dorsal
      premotor to primary motor cortex in the left hemisphere are stronger during
      imitation than during observation. The first two connections are implicated in a
      putative dorsal stream of speech perception, thought to involve translating
      auditory speech signals into motor representations. Thus, the current results
      suggest that flow of information during imitation, starting at the posterior
      superior temporal cortex and ending in the motor cortex, enhances input to the
      motor cortex in the service of speech execution.

PMID- 22470362
TI  - Holistic Representations of Internal and External Face Features are Used to
      Support Recognition.
AB  - Face recognition is impaired when changes are made to external face features
      (e.g., hairstyle), even when all internal features (i.e., eyes, nose, mouth)
      remain the same. Eye movement monitoring was used to determine the extent to
      which altered hairstyles affect processing of face features, thereby shedding
      light on how internal and external features are stored in memory. Participants
      studied a series of faces, followed by a recognition test in which novel,
      repeated, and manipulated (altered hairstyle) faces were presented. Recognition
      was higher for repeated than manipulated faces. Although eye movement patterns
      distinguished repeated from novel faces, viewing of manipulated faces was similar
      to that of novel faces. Internal and external features may be stored together as
      one unit in memory; consequently, changing even a single feature alters
      processing of the other features and disrupts recognition.

PMID- 22470361
TI  - The effects of aerobic activity on brain structure.
AB  - Aerobic activity is a powerful stimulus for improving mental health and for
      generating structural changes in the brain. We review the literature documenting
      these structural changes and explore exactly where in the brain these changes
      occur as well as the underlying substrates of the changes including neural,
      glial, and vasculature components. Aerobic activity has been shown to produce
      different types of changes in the brain. The presence of novel experiences or
      learning is an especially important component in how these changes are manifest.
      We also discuss the distinct time courses of structural brain changes with both
      aerobic activity and learning as well as how these effects might differ in
      diseased and elderly groups.

PMID- 22470363
TI  - The right thing at the right time: why ostensive naming facilitates word
      learning.
AB  - The current study examines how focusing children's attention immediately after
      fast mapping improves their ability to retain novel names. Previous research
      suggests that young children can only retain novel names presented via referent
      selection if ostensive naming is provided and that such explicit naming works by
      increasing children's attention to the target and decreasing their attention to
      the competitor objects (Horst and Samuelson, 2008). This explanation of the
      function of ostensive naming after referent selection trials was tested by
      drawing 24-month-old children's attention to the target either by illuminating
      the target, covering the competitors, or both. A control group was given a social
      pragmatic cue (pointing). Children given social pragmatic cue support did not
      demonstrate retention. However, children demonstrated retention if the target
      object was illuminated, and also when it was illuminated and the competitors
      simultaneously dampened. This suggests that drawing children's attention to the
      target object in a manner that helps focus children's attention is critical for
      word learning via referent selection. Directing attention away from competitors
      while also directing attention toward a target also aids in the retention of
      novel words.

PMID- 22470364
TI  - A Device for the Functional Evaluation of the VOR in Clinical Settings.
AB  - We developed the head impulse testing device (HITD) based on an inertial sensing
      system allowing to investigate the functional performance of the rotational
      vestibulo-ocular reflex (VOR) by testing its gaze stabilization ability,
      independently from the subject's visual acuity, in response to head impulses at
      different head angular accelerations ranging from 2000 to 7000 deg/s(2). HITD was
      initially tested on 22 normal subjects, and a method to compare the results from
      a single subject (patient) with those from controls was set up. As a pilot study,
      we tested the HITD in 39 dizzy patients suffering, non-acutely, from different
      kinds of vestibular disorders. The results obtained with the HITD were comparable
      with those from the clinical head impulse test (HIT), but an higher number of
      abnormalities was detectable by HITD in the central vestibular disorders group.
      The HITD appears to be a promising tool for detecting abnormal VOR performance
      while providing information on the functional performance of the rotational VOR,
      and can provide a valuable assistance to the clinical evaluation of patients with
      vestibular disorders.

PMID- 22470365
TI  - Challenging New Targets for CNS-HIV Infection.
AB  - THE CENTRAL NERVOUS SYSTEM (CNS) REPRESENTS AN IMPORTANT TARGET FOR HIV INFECTION
      DURING MULTIPLE STAGES OF THE DISEASE: early, after invasion of the host, acting
      as a viral reservoir; lately, subverting its function and causing peripheral
      neuropathies and neurocognitive disorders; and lastly, during the final stage of
      NeuroAIDS, triggering opportunistic infections, cancers, and dementia. Highly
      active antiretroviral therapy, a combination of drugs that inhibits enzymes
      essential for HIV replication, can reduce the viremia and the onset of
      opportunistic infections in most patients, and prolong the survival. Among the
      limits of the current treatments the most noticeable is the inability to
      eradicate HIV-infected cells, both, limiting the time frame in which
      antiretroviral therapies initiated after exposure to HIV can prevent infection,
      and allowing replication-competent virus that persists in infected cells to
      emerge rapidly after the cessation of treatments. Many strategies are currently
      under evaluation to improve HIV treatment, unfortunately more than 98% of drug
      candidates for CNS disorders never make it to the clinic; here in we report how
      nanoformulated strategies might be adapted and applied to the field of CNS-HIV
      infection.

PMID- 22470366
TI  - Rethinking Alzheimer's disease.

PMID- 22470367
TI  - A Multiscale Approach to Blast Neurotrauma Modeling: Part I - Development of
      Novel Test Devices for in vivo and in vitro Blast Injury Models.
AB  - The loading conditions used in some current in vivo and in vitro blast-induced
      neurotrauma models may not be representative of real-world blast conditions. To
      address these limitations, we developed a compressed-gas driven shock tube with
      different driven lengths that can generate Friedlander-type blasts. The shock
      tube can generate overpressures up to 650 kPa with durations between 0.3 and 1.1
      ms using compressed helium driver gas, and peak overpressures up to 450 kPa with
      durations between 0.6 and 3 ms using compressed nitrogen. This device is used for
      short-duration blast overpressure loading for small animal in vivo injury models,
      and contrasts the more frequently used long duration/high impulse blast
      overpressures in the literature. We also developed a new apparatus that is used
      with the shock tube to recreate the in vivo intracranial overpressure response
      for loading in vitro culture preparations. The receiver device surrounds the
      culture with materials of similar impedance to facilitate the propagation of a
      single overpressure pulse through the tissue. This method prevents pressure waves
      reflecting off the tissue that can cause unrealistic deformation and injury. The
      receiver performance was characterized using the longest helium-driven shock
      tube, and produced in-fluid overpressures up to 1500 kPa at the location where a
      culture would be placed. This response was well correlated with the overpressure
      conditions from the shock tube (R(2) = 0.97). Finite element models of the shock
      tube and receiver were developed and validated to better elucidate the mechanics
      of this methodology. A demonstration exposing a culture to the loading conditions
      created by this system suggest tissue strains less than 5% for all pressure
      levels simulated, which was well below functional deficit thresholds for strain
      rates less than 50 s(-1). This novel system is not limited to a specific type of
      culture model and can be modified to reproduce more complex pressure pulses.

PMID- 22470368
TI  - Carbon, metals, and grain size correlate with bacterial community structure in
      sediments of a high arsenic aquifer.
AB  - Bacterial communities can exert significant influence on the biogeochemical
      cycling of arsenic (As). This has globally important implications since As in
      drinking water affects the health of over 100 million people worldwide, including
      in the Ganges-Brahmaputra Delta region of Bangladesh where geogenic arsenic in
      groundwater can reach concentrations of more than 10 times the World Health
      Organization's limit. Thus, the goal of this research was to investigate patterns
      in bacterial community composition across gradients in sediment texture and
      chemistry in an aquifer with elevated groundwater As concentrations in Araihazar,
      Bangladesh. We characterized the bacterial community by pyrosequencing 16S rRNA
      genes from aquifer sediment samples collected at three locations along a
      groundwater flow path at a range of depths between 1.5 and 15 m. We identified
      significant differences in bacterial community composition between locations in
      the aquifer. In addition, we found that bacterial community structure was
      significantly related to sediment grain size, and sediment carbon (C), manganese
      (Mn), and iron (Fe) concentrations. Deltaproteobacteria and Chloroflexi were
      found in higher proportions in silty sediments with higher concentrations of C,
      Fe, and Mn. By contrast, Alphaproteobacteria and Betaproteobacteria were in
      higher proportions in sandy sediments with lower concentrations of C and metals.
      Based on the phylogenetic affiliations of these taxa, these results may indicate
      a shift to more Fe-, Mn-, and humic substance-reducers in the high C and metal
      sediments. It is well-documented that C, Mn, and Fe may influence the mobility of
      groundwater arsenic, and it is intriguing that these constituents may also
      structure the bacterial community.

PMID- 22470369
TI  - The effect of nitrogen enrichment on c(1)-cycling microorganisms and methane flux
      in salt marsh sediments.
AB  - Methane (CH(4)) flux from ecosystems is driven by C(1)-cycling microorganisms -
      the methanogens and the methylotrophs. Little is understood about what regulates
      these communities, complicating predictions about how global change drivers such
      as nitrogen enrichment will affect methane cycling. Using a nitrogen addition
      gradient experiment in three Southern California salt marshes, we show that
      sediment CH(4) flux increased linearly with increasing nitrogen addition (1.23
      MUg CH(4) m(-2) day(-1) for each g N m(-2) year(-1) applied) after 7 months of
      fertilization. To test the reason behind this increased CH(4) flux, we conducted
      a microcosm experiment altering both nitrogen and carbon availability under
      aerobic and anaerobic conditions. Methanogenesis appeared to be both nitrogen and
      carbon (acetate) limited. N and C each increased methanogenesis by 18%, and
      together by 44%. In contrast, methanotrophy was stimulated by carbon (methane)
      addition (830%), but was unchanged by nitrogen addition. Sequence analysis of the
      sediment methylotroph community with the methanol dehydrogenase gene (mxaF)
      revealed three distinct clades that fall outside of known lineages. However, in
      agreement with the microcosm results, methylotroph abundance (assayed by qPCR)
      and composition (assayed by terminal restriction fragment length polymorphism
      analysis) did not vary across the experimental nitrogen gradient in the field.
      Together, these results suggest that nitrogen enrichment to salt marsh sediments
      increases methane flux by stimulating the methanogen community.

PMID- 22470370
TI  - Population Dynamics of Borrelia burgdorferi in Lyme Disease.
AB  - Many chronic inflammatory diseases are known to be caused by persistent bacterial
      or viral infections. A well-studied example is the tick-borne infection by the
      gram-negative spirochaetes of the genus Borrelia in humans and other mammals,
      causing severe symptoms of chronic inflammation and subsequent tissue damage
      (Lyme Disease), particularly in large joints and the central nervous system, but
      also in the heart and other tissues of untreated patients. Although killed
      efficiently by human phagocytic cells in vitro, Borrelia exhibits a remarkably
      high infectivity in mice and men. In experimentally infected mice, the first
      immune response almost clears the infection. However, approximately 1 week post
      infection, the bacterial population recovers and reaches an even larger size
      before entering the chronic phase. We developed a mathematical model describing
      the bacterial growth and the immune response against Borrelia burgdorferi in the
      C3H mouse strain that has been established as an experimental model for Lyme
      disease. The peculiar dynamics of the infection exclude two possible mechanistic
      explanations for the regrowth of the almost cleared bacteria. Neither the
      hypothesis of bacterial dissemination to different tissues nor a limitation of
      phagocytic capacity were compatible with experiment. The mathematical model
      predicts that Borrelia recovers from the strong initial immune response by the
      regrowth of an immune-resistant sub-population of the bacteria. The chronic phase
      appears as an equilibration of bacterial growth and adaptive immunity. This
      result has major implications for the development of the chronic phase of
      Borrelia infections as well as on potential protective clinical interventions.

PMID- 22470371
TI  - Cellular receptors for human enterovirus species a.
AB  - Human enterovirus species A (HEV-A) is one of the four species of HEV in the
      genus Enterovirus in the family Picornaviridae. Among HEV-A, coxsackievirus A16
      (CVA16) and enterovirus 71 (EV71) are the major causative agents of hand, foot,
      and mouth disease (HFMD). Some other types of HEV-A are commonly associated with
      herpangina. Although HFMD and herpangina due to HEV-A are common febrile diseases
      among infants and children, EV71 can cause various neurological diseases, such as
      aseptic meningitis and fatal encephalitis. Recently, two human transmembrane
      proteins, P-selectin glycoprotein ligand-1 (PSGL-1) and scavenger receptor class
      B, member 2 (SCARB2), were identified as functional receptors for EV71 and CVA16.
      In in vitro infection experiments using the prototype HEV-A strains, PSGL-1 and
      SCARB2 could be responsible for the specific receptors for EV71 and CVA16.
      However, the involvement of both receptors in the in vitro and in vivo infections
      of clinical isolates of HEV-A has not been clarified yet. To elucidate a diverse
      array of the clinical outcome of HEV-A-associated diseases, the identification
      and characterization of HEV-A receptors may provide useful information in
      understanding the HEV-A pathogenesis at a molecular level.

PMID- 22470372
TI  - Microbial iron cycling in acidic geothermal springs of yellowstone national park:
      integrating molecular surveys, geochemical processes, and isolation of novel fe
      active microorganisms.
AB  - Geochemical, molecular, and physiological analyses of microbial isolates were
      combined to study the geomicrobiology of acidic iron oxide mats in Yellowstone
      National Park. Nineteen sampling locations from 11 geothermal springs were
      studied ranging in temperature from 53 to 88 degrees C and pH 2.4 to 3.6. All
      iron oxide mats exhibited high diversity of crenarchaeal sequences from the
      Sulfolobales, Thermoproteales, and Desulfurococcales. The predominant
      Sulfolobales sequences were highly similar to Metallosphaera yellowstonensis str.
      MK1, previously isolated from one of these sites. Other groups of archaea were
      consistently associated with different types of iron oxide mats, including
      undescribed members of the phyla Thaumarchaeota and Euryarchaeota. Bacterial
      sequences were dominated by relatives of Hydrogenobaculum spp. above 65-70
      degrees C, but increased in diversity below 60 degrees C. Cultivation of relevant
      iron-oxidizing and iron-reducing microbial isolates included Sulfolobus str. MK3,
      Sulfobacillus str. MK2, Acidicaldus str. MK6, and a new candidate genus in the
      Sulfolobales referred to as Sulfolobales str. MK5. Strains MK3 and MK5 are
      capable of oxidizing ferrous iron autotrophically, while strain MK2 oxidizes iron
      mixotrophically. Similar rates of iron oxidation were measured for M.
      yellowstonensis str. MK1 and Sulfolobales str. MK5. Biomineralized phases of
      ferric iron varied among cultures and field sites, and included ferric
      oxyhydroxides, K-jarosite, goethite, hematite, and scorodite depending on
      geochemical conditions. Strains MK5 and MK6 are capable of reducing ferric iron
      under anaerobic conditions with complex carbon sources. The combination of
      geochemical and molecular data as well as physiological observations of isolates
      suggests that the community structure of acidic Fe mats is linked with Fe cycling
      across temperatures ranging from 53 to 88 degrees C.

PMID- 22470373
TI  - Exploring the molecular basis of antifungal synergies using genome-wide
      approaches.
AB  - Drug resistance poses a significant challenge in antifungal therapy since
      resistance has been found for all known classes of antifungal drugs. The
      discovery of compounds that can act synergistically with antifungal drugs is an
      important strategy to overcome resistance. For such combination therapies to be
      effective, it is critical to understand the molecular basis for the synergism by
      examining the cellular effects exerted by the combined drugs. Genomic profiling
      technologies developed in the model yeast Saccharomyces cerevisiae have been
      successfully used to investigate antifungal combinations. This review discusses
      how these technologies have been used not only to identify synergistic mechanisms
      but also to predict drug synergies. It also discusses how genome-wide genetic
      interaction studies have been combined with drug-target information to
      differentiate between antifungal drug synergies that are target-specific versus
      those that are non-specific. The investigation of the mechanism of action of
      antifungal synergies will undoubtedly advance the development of optimal and safe
      combination therapies for the treatment of drug-resistant fungal infections.

PMID- 22470374
TI  - QT Interval and QT Dispersion in Patients Undergoing Hemodialysis: Revisiting the
      Old Theory.
AB  - AIMS: We sought to explore the response of the corrected QT (QTc) interval
      duration and QT dispersion (QTD) to hemodialysis. METHODS: We enrolled 50
      patients with end-stage renal disease undergoing regular hemodialysis. Blood
      samples were drawn for measurement of serum electrolytes, and a 12-lead ECG was
      performed to measure the QTc interval duration and QTD, immediately before and
      just after dialysis sessions. RESULTS: The mean age of the cohort was 42.8 +/-
      12.2 years (58% males). Both the QTc duration and QTD showed marked variability
      after hemodialysis. A significant correlation was found between the decrease of
      both serum potassium and magnesium levels after dialysis and the post-dialysis
      QTc interval duration, with Pearson's correlation coefficients r = -0.43 and r = 
      0.34, p = 0.002 and p = 0.01, respectively. Patients with a post-dialysis
      increase of QTc interval duration had a significantly higher percentage of
      reduction of serum potassium (p = 0.029), whereas patients with a post-dialysis
      increase of QTD had a significantly higher percentage of reduction of serum
      magnesium (p = 0.03). CONCLUSION: Our findings suggest a highly variable response
      of the QTc interval duration and QTD to hemodialysis. The post-dialysis QTc
      interval duration inversely correlated with the decrease of both serum potassium
      and magnesium levels after dialysis.

PMID- 22470375
TI  - Urinary Neutrophil Gelatinase-Associated Lipocalin Measured on Admission to the
      Intensive Care Unit Accurately Discriminates between Sustained and Transient
      Acute Kidney Injury in Adult Critically Ill Patients.
AB  - BACKGROUND: First we aimed to evaluate the ability of neutrophil gelatinase
      associated lipocalin (NGAL) and cystatin-C (CyC) in plasma and urine to
      discriminate between sustained, transient and absent acute kidney injury (AKI),
      and second to evaluate their predictive performance for sustained AKI in adult
      intensive care unit (ICU) patients. METHODS: A prospective cohort study of 700
      patients was studied. Sample collection was performed over 8 time points starting
      on admission. RESULTS: After exclusion 510 patients remained for the analysis.
      All biomarkers showed significant differentiation between sustained and no AKI at
      all time points (p <= 0.0002) except for urine CyC (uCyC) on admission (p =
      0.06). Urine NGAL (uNGAL) was the only biomarker significantly differentiating
      sustained from transient AKI on ICU admission (p = 0.02). Individually, uNGAL
      performed better than the other biomarkers (area under the curves, AUC = 0.80,
      95% confidence interval, CI = 0.72-0.88) for the prediction of sustained AKI. The
      combination with plasma NGAL (pNGAL) showed a nonsignificant improvement (AUC =
      0.83, 95% CI = 0.75-0.91). The combination of individual markers with a model of
      clinical characteristics (MDRD eGFR, HCO(3) (-) and sepsis) did not improve its
      performance significantly. However, the integrated discrimination improvement
      showed significant improvement when uNGAL was added (p = 0.04). CONCLUSIONS:
      uNGAL measured on ICU admission differentiates patients with sustained AKI from
      transient or no-AKI patients. Combining biomarkers such as pNGAL, uNGAL and
      plasma CyC with clinical characteristics adds some value to the predictive model.

PMID- 22470376
TI  - Low doses of cadmium chloride and methallothionein-1-bound cadmium display
      different accumulation kinetics and induce different genes in cells of the human
      nephron.
AB  - BACKGROUND/AIMS: The present study was conducted to investigate the renal tubular
      handling of inorganic cadmium (Cd(2+)) by exposing primary human tubular cell
      cultures to physiologically relevant doses of cadmium chloride (CdCl(2)).
      Furthermore, the cellular accumulation of Cd(2+) was compared to that of
      metallothionein-1-bound Cd (Cd7MT-1). Finally, this study aimed to investigate
      the effect of the accumulation of Cd (both Cd(2+) and Cd7MT-1) in renal cells on
      the expression of genes relevant to nephrotoxic processes. METHODS: Cd
      concentration was measured using atomic absorption spectrometry. mRNA expression
      was evaluated by quantitative real-time RT-PCR. RESULTS: Cd(2+) accumulated into
      human tubular cells in a concentration- and time-dependent way. Furthermore,
      cellular accumulation of Cd(2+) was different from the cellular accumulation of
      Cd7MT-1, indicative for different uptake routes. Finally, mRNA expression of the
      genes encoding the anti-oxidative proteins metallothionein-1 (MT-1) and heme
      oxygenase-1 (HO-1) as well as the pro-apoptotic Bcl-2-associated X protein (Bax)
      were upregulated by CdCl(2) and not by Cd7MT1. CONCLUSION: In the presence of
      physiologically relevant Cd concentrations, tubular accumulation of the element
      in its inorganic form is different from that of Cd7MT-1. Furthermore, the tubular
      accumulation of inorganic Cd induces mRNA expression of genes of which the
      protein products may play a role in Cd-associated renal toxicity.

PMID- 22470377
TI  - Reference renal artery diameter is a stronger predictor of contrast-induced
      nephropathy than chronic kidney disease in patients with high cardiovascular
      risk.
AB  - INTRODUCTION: The incidence of contrast-induced nephropathy (CIN) increases in
      high cardiovascular risk patients. Chronic kidney disease (CKD) is a known risk
      factor for CIN development. In a previous report, we demonstrated that the mean
      reference renal artery diameter (RVD) is an important determinant of CKD in
      patients undergoing coronary angiography for ischemic heart disease. However, RVD
      was never tested as a predictor of CIN. AIM: To look at the predictors of CIN.
      METHODS: A total of 218 consecutive patients undergoing coronary and renal
      angiography were enrolled from the cohort of the RAS-CAD study (NCT 01173666).
      CIN was defined as a relative increase in baseline serum creatinine >=25% within
      1 week of contrast administration. RESULTS: The incidence of CIN was 22%. In a
      fully adjusted model, contrast medium dose (20 ml increase, OR 1.12, 95% CI 1.06
      1.19, p < 0.001), iso-osmolar contrast media (OR 0.28, 95% CI 0.09-0.99, p <
      0.05), atherosclerotic renovascular disease (OR 2.69, 95% CI 1.32-5.48, p <
      0.05), and RVD (1 mm/1.73 m(2) increase, OR 0.59, 95% CI 0.41-0.86, p < 0.05) had
      the greatest effect on outcome and were identified as independent predictors of
      CIN. CKD was selected as a predictor of CIN only in a model without RVD.
      CONCLUSIONS: In patients undergoing coronary angiography for ischemic heart
      disease, RVD is a stronger predictor of CIN than CKD.

PMID- 22470378
TI  - Dosing of erythropoiesis-stimulating agents can be reduced by a new
      administration regimen.
AB  - BACKGROUND/AIMS: At our hemodialysis (HD) unit, we noted a drop in the treatment
      dose of erythropoietin-stimulating agents (ESAs) when the frequency of dose
      adjustment was reduced from weekly, where doses were withheld if hemoglobin was
      >130 g/l, to monthly, where doses were not withheld. The aim of this study was to
      find an explanation for this reduction in ESA requirement. METHODS: This is a
      retrospective study on 18 stable HD patients. Comparable follow-up periods of 6
      months with the two different ESA adjustment regimens were established and data
      on ESA dose, hemoglobin and known predictors of ESA response were collected.
      RESULTS: With the new ESA administration regimen, a 22.5% drop in the total ESA
      dose was noted. The corresponding fall in the erythropoietin resistance index was
      20.0%. Simultaneously, the dialysis dose and transferrin saturation increased
      significantly. However, in a multivariate linear regression model, changes in
      these factors did not significantly predict changes in ESA requirement. No
      relevant changes were noted in other erythropoiesis-modulating factors.
      CONCLUSION: Frequent dose adjustments and the current ESA administration practice
      of withholding ESA doses does not seem to reduce ESA demand. On the contrary,
      such practice is likely to increase ESA requirement over time.

PMID- 22470379
TI  - Quantitative estimation of urate transport in nephrons in relation to urinary
      excretion employing benzbromarone-loading urate clearance tests in cases of
      hyperuricemia.
AB  - BACKGROUND: A four-component system for urate transport in nephrons has been
      proposed and widely investigated by various investigators studying the mechanisms
      underlying urinary urate excretion. However, quantitative determinations of urate
      transport have not been clearly elucidated yet. METHODS: The equation C(ua) =
      {C(cr)(1 - R(1)) + TSR}(1 - R(2)) was designed to approximate mathematically
      urate transport in nephrons, where R(1) = urate reabsorption ratio; R(2) = urate
      postsecretory reabsorption ratio; TSR = tubular secretion rate; C(ua) = urate
      clearance, and C(cr) = creatinine clearance. To investigate relationships between
      the three unknown variables (R(1), R(2), and TSR), this equation was expressed as
      contour lines of one unknown on a graph of the other two unknowns. Points at
      regular intervals on each contour line for the equation were projected onto a
      coordinate axis and the high-density regions corresponding to high-density
      intervals of a coordinate were investigated for three graph types. For
      benzbromarone (BBR)-loading C(ua) tests, C(ua) was determined before and after
      oral administration of 100 mg of BBR and C(ua)BBR(infinity) was calculated from
      the ratio of C(ua)BBR(100)/C(ua). RESULTS: Before BBR administration, points
      satisfying the equation on the contour line for R(1) = 0.99 were highly dense in
      the region R(2) = 0.87-0.92 on all three graphs, corresponding to a TSR of 40-60
      ml/min in hyperuricemia cases (HU). After BBR administration, the dense region
      was shifted in the direction of reductions in both R(1) and R(2), but TSR was
      unchanged. Under the condition that R(1) = 1 and R(2) = 0, urate tubular
      secretion (UTS) was considered equivalent to calculated urinary urate excretion
      (U(ex)) in a model of intratubular urate flow with excess BBR; C(ua)BBR(infinity)
      = TSR was deduced from the equation at R(1) = 1 and R(2) = 0. In addition, TSR of
      the point under the condition that R(1) = 1 and R(2) = 0 on the graph agreed with
      TSR for the dense region at excess BBR. TSR was thus considered approximately
      equivalent to C(ua)BBR(infinity), which could be determined from a BBR-loading
      C(ua) test. Approximate values for urate glomerular filtration, urate
      reabsorption, UTS, urate postsecretory reabsorption (UR(2)), and U(ex) were
      calculated as 9,610; 9,510; 4,490; 4,150, and 440 MUg/min for HU and 6,890;
      6,820; 4,060; 3,610, and 520 MUg/min for normal controls (NC), respectively. The
      most marked change in HU was the decrease in TSR (32.0%) compared to that in NC,
      but UTS did not decrease. Calculated intratubular urate contents were reduced
      more by higher UR(2) in HU than in NC. This enhanced difference resulted in a
      15.4% decrease in U(ex) for HU. CONCLUSION: Increased UR(2) may represent the
      main cause of urate underexcretion in HU.

PMID- 22470380
TI  - Crescentic glomerulonephritis in IgA multiple myeloma: a case report.
AB  - BACKGROUND: There are few reports of glomerulonephritis (GN) with crescents and a
      rapidly progressive course that lead to a diagnosis of a previously unsuspected B
      cell dyscrasia. CASE PRESENTATION: We report a case of rapidly progressive GN:
      the patient showed no evidence of etiology at the time of biopsy and was
      diagnosed as IgA multiple myeloma (MM) during investigation based on a renal
      biopsy. He presented diffuse proliferative and exudative GN and marked plasma
      cell infiltration of the kidney. CONCLUSION: The present case raises the
      possibility that proliferative GN with crescents may be a rare mode of
      presentation of MM.

PMID- 22470381
TI  - Oxidative stress in cystinosis patients.
AB  - BACKGROUND/AIMS: Nephropathic cystinosis (NC) is a severe systemic disease and
      cysteamine improves its prognosis. Lysosomal cystine accumulation is the hallmark
      of cystinosis and is regarded as the primary defect due to mutations in the CTNS
      gene. However, there is great evidence that cystine accumulation itself is not
      responsible for all abnormalities observed in NC. Studies have demonstrated
      altered ATP metabolism, increased apoptosis, and cell oxidation. An increased
      number of autophagosomes and autophagic vacuoles have been observed in cystinotic
      fibroblasts and renal epithelial cells, suggesting that altered autophagy plays a
      role in NC, leading to increased production of reactive oxygen species.
      Therefore, cystinosis patients can be more susceptible to oxidative stress (OS)
      and it can contribute to the progression of the renal disease. Our goal was to
      evaluate a marker of OS (serum TBARS) in NC children, and to compare the results
      with those observed in healthy controls and correlated with renal function
      parameters. METHODS: The study included patients aged under 18 years, with good
      adherence to the treatment and out of renal replacement therapy. The following
      parameters were evaluated: serum creatinine, BUN, creatinine clearance estimated
      by stature and serum TBARS levels. RESULTS: We selected 20 patients aged 8.0 +/
      3.6 years and observed serum TBARS levels of 4.03 +/-1.02 nmol/ml. Serum TBARS
      levels in the 43 healthy controls, aged 7.4 +/-1.1 years, were 1.60 +/-0.04
      nmol/ml. There was a significant difference between the plasma TBARS levels among
      the 2 groups (p < 0.0001). We detected no significant correlation between plasma
      TBARS levels and renal function. CONCLUSION: An increased level of serum TBARS in
      patients with NC was observed and this abnormality was not correlated with the
      renal function status degree. This is the first report that shows increased
      oxidative stress in serum of NC patients.

PMID- 22470382
TI  - Attenuation of Immune-Mediated Renal Injury by Telmisartan, an Angiotensin
      Receptor Blocker and a Selective PPAR-gamma Activator.
AB  - BACKGROUND/AIMS: Anti-glomerular basement membrane (GBM) nephritis is
      characterized by activation of the renin-angiotensin system. This study aimed to
      determine the question of whether a temporary angiotensin II blockade at the
      initial stage of anti-GBM nephritis is able to attenuate the disease as well as
      differences in renoprotection among angiotensin II receptor blockers (ARBs) with
      distinct peroxisome proliferator-activated receptor (PPAR)-gamma-modulating
      activities. METHODS: C57BL/6J mice were immunized with rabbit IgG, followed by
      intravenous injection of rabbit anti-mouse antibodies. Mice were then treated
      with telmisartan, losartan, and telmisartan + GW9662 (a PPAR-gamma antagonist)
      for 5 days, or hydralazine for 9 days. On days 8 and 13, mice were sacrificed to
      obtain tissues for histological analysis. RESULTS: The temporary administration
      of telmisartan significantly suppressed glomerular damage compared to
      hydralazine. Losartan showed a similar effect but was less effective. Co
      administration of GW9662 attenuated the renoprotective effect of telmisartan,
      almost to levels observed with losartan. In particular, it limited the decreased
      infiltration of inflammatory cells and preservation of capillaries in the
      glomeruli induced by telmisartan. CONCLUSION: Temporary angiotensin II blockade
      at the initial stage of anti-GBM disease dramatically inhibited its progression.
      In addition to a class effect of ARBs, telmisartan modified inflammation and
      endothelial damage in the kidney through its PPAR-gamma-agonistic action.

PMID- 22470383
TI  - Determinants of outcome in non-septic critically ill patients with acute kidney
      injury on continuous venovenous hemofiltration.
AB  - BACKGROUND/AIMS: In view of ongoing controversy, we wished to study whether
      patient characteristics and/or continuous venovenous hemofiltration (CVVH)
      characteristics contribute to the outcome of non-septic critically ill patients
      with acute kidney injury (AKI). METHODS: We retrospectively studied 102
      consecutive patients in the intensive care unit (ICU) with non-septic AKI needing
      CVVH. Patient and CVVH characteristics were evaluated. Primary outcome was
      mortality up to day 28 after CVVH initiation. RESULTS: Forty-four patients (43%)
      died during the 28-day period after the start of CVVH. In univariate analyses,
      non-survivors had more often a cardiovascular reason for ICU admission, greater
      disease acuity/severity and organ failure, lower initial creatinine levels, less
      use of heparin and more use of bicarbonate-based substitution fluid. The latter
      two can be attributed to high lactate levels and bleeding tendency in non
      survivors necessitating withholding lactate-buffered fluid and heparin,
      respectively, according to our clinical protocol. In multivariate analyses,
      mortality was predicted by disease severity, use of bicarbonate-based fluids and
      lack of heparin, while initial creatinine and CVVH dose did not contribute.
      CONCLUSION: The outcome of non-septic AKI in need of CVVH is more likely to be
      determined by underlying or concurrent, acute and severe disease rather than by
      CVVH characteristics, including timing and dose.

PMID- 22470384
TI  - Early treatment with methylprednisolone pulse therapy combined with tonsillectomy
      for heavy proteinuric henoch-schonlein purpura nephritis in children.
AB  - BACKGROUND: There is no clear consensus as to which patients with Henoch
      Schonlein purpura nephritis (HSPN) at risk of a poor outcome should be treated
      and what therapeutic regimen should be used. METHODS: Nine children with heavy
      proteinuric HSPN received prompt initiation of methylprednisolone pulse therapy
      (MPT) combined with tonsillectomy in a prospective study. RESULTS: At
      presentation, the mean values for the patients' urine protein excretion (early
      morning urinary protein/creatinine ratio), serum IgA, activity index (AI), and
      chronicity index (CI) were 5.0 +/- 5.6 g/g Cr, 135.6 +/- 56.5 mg/dl, 4.0 +/- 0.7,
      and 1.7 +/- 1.3, respectively. At the second biopsy, conducted approximately 24
      months after initiation of therapy, the patients' serum albumin had significantly
      increased (4.4 +/- 0.2, p < 0.01), and the serum IgA and AI had significantly
      decreased (88.1 +/- 30.8 mg/dl, p < 0.05; 2.0 +/- 1.2, p < 0.01, respectively),
      whereas the CI remained unchanged. Proteinuria disappeared within 24 months in
      all but 1 patient, and hematuria disappeared within 38 months in all patients. No
      patient showed renal impairment or experienced a recurrence and/or exacerbation
      of HSP/HSPN. CONCLUSIONS: Early treatment with MPT combined with tonsillectomy is
      effective in ameliorating the histopathological progression and improving the
      clinical course of children with heavy proteinuric HSPN.

PMID- 22470385
TI  - CYBA Gene Polymorphisms and Adverse Outcomes in Acute Kidney Injury: A
      Prospective Cohort Study.
AB  - BACKGROUND: NADPH oxidase is an important enzyme involved in the generation of
      reactive oxygen species in acute kidney injury (AKI). Its key subunit, p22(phox),
      is encoded by the highly polymorphic CYBA gene. METHODS: We examined the
      associations of CYBA gene polymorphisms across the CYBA locus (rs8854, rs3794624,
      rs4673, rs4782390, and rs1049255) with dialysis requirement or in-hospital death
      in 256 hospitalized adults with AKI. Dominant and haplotype multivariable
      logistic regression analyses were performed, adjusted for sex, race, age, and
      severity of illness. RESULTS: The baseline characteristics of the patients were
      not different among genotype groups with the exception of a lower prevalence of
      sepsis and shock in the CYBA rs8854 A-allele group; a higher prevalence of shock
      in the CYBA rs4782390 T-allele group, and a higher APACHE II score in the CYBA
      rs1049255 G-allele group. The CYBA rs8854 A-allele had an adjusted odds ratio
      (OR) of 0.41 (95% confidence interval, CI, 0.18-0.96) for the outcome of dialysis
      requirement or in-hospital death. The CYBA rs4673 T-allele and rs1049255 G-allele
      had unadjusted ORs of 1.69 (95% CI 1.03-2.79) and 1.66 (95% CI 1.01-2.73) for the
      composite outcome, respectively, which became non-significant after multivariable
      adjustment. The remaining 2 polymorphisms were not associated with the outcomes
      of interest. Finally, the presence of the CYBA A-A-G-G haplotype (generated from
      rs4782390, rs4673, rs3794624, and rs8854, all in Hardy-Weinberg equilibrium) was
      associated with an elevated OR of 1.81 (95% CI 1.07-3.08) for dialysis
      requirement or in-hospital death, which was attenuated after multivariable
      adjustment (OR 1.80; 95% CI 0.99-3.29). CONCLUSION: This study identifies several
      polymorphisms spanning the entire CYBA gene locus and a common haplotype as risk
      markers for dialysis requirement or in-hospital death in patients with AKI.
      Additional studies are needed to validate these findings.

PMID- 22470386
TI  - Aquaporin-2 promoter is synergistically regulated by nitric oxide and nuclear
      factor of activated T cells.
AB  - BACKGROUND/AIMS: We have previously shown that aquaporin-2 (AQP2) is down
      regulated in the renal medulla of rats made hypertensive by chronic inhibition of
      nitric oxide synthase. It has been shown that AQP2 expression is regulated by the
      calcineurin/nuclear factor of activated T cells (NFATc). Nitric oxide (NO)
      regulates the activity of NFATc via c-Jun-N-terminal kinase 2 (JNK2). Therefore,
      we hypothesized that increases in NO enhance NFATc-mediated up-regulation of AQP2
      promoter activity. METHODS: AQP2 mRNA and protein expression were detected in
      mouse renal papilla. AQP2 promoter luciferase reporter- and NFAT luciferase
      reporter-transfected MDCK cells were used to determine AQP2 promoter activity and
      NFATc activity, respectively. Cells were incubated with classic activators and
      inhibitors of NFATc and the NO pathway. RESULTS: Our results demonstrate that
      both Ca(2+) and NO have a synergistic effect resulting in an increase in AQP2
      mRNA and protein in mouse papilla and activation of the AQP2 promoter in kidney
      derived cells. In addition, NO enhances Ca(2+)-induced NFATc activation. The
      underlying mechanism involves increased NFATc nuclear import and decreased export
      via protein kinase G-mediated inhibition of JNK1/2. CONCLUSIONS: This is the
      first study defining novel regulatory roles for NO and NFATc in the control of
      AQP2, which is an important renal protein.

PMID- 22470387
TI  - Effects of tridocosahexaenoyl-glycerol emulsion on proteinuria in rats with
      nephrotoxic serum nephritis.
AB  - BACKGROUND: Docosahexaenoic acid (DHA) is one of the n-3 polyunsaturated fatty
      acids and an important component of cell membrane phospholipids (PL). Nephrotoxic
      serum (NTS) nephritis was a worldwide model of the Goodpasture syndrome. We
      investigated the effects of tridocosahexaenoyl-glycerol (DHA-TG) emulsion on
      proteinuria in rats with NTS nephritis. METHODS: Sixteen male Wistar rats
      weighing approximately 200 g were used. Twelve rats were treated with NTS via the
      tail vein and divided into 3 groups (groups A, B, and C). Another 4 rats treated
      with saline served as controls (group D). DHA-TG and soybean oil emulsions were
      intraperitoneally administered to the rats in groups A and B, respectively, 24 h
      prior to NTS injection, and 0, 1, 2, 3, 4, and 5 days after the injection. Saline
      was administered to the rats in groups C and D in the same manner. All rats were
      sacrificed on day 6 to obtain plasma and kidney samples. Analyses of urinary
      protein levels and fatty acid composition of plasma and kidney as well as
      histological examination of the kidneys were performed. RESULTS: Urinary protein
      levels in group A were significantly lower than those in group C (35.0 +/- 13.3
      vs. 79.2 +/- 11.8 mg/day on day 5, means +/- SE, p < 0.05). DHA levels in the PL
      fraction of the kidneys in group A were significantly increased compared with
      those in groups B and C. CONCLUSIONS: These results suggest that the DHA-TG
      emulsion may have beneficial effects on NTS nephritis in the rat.

PMID- 22470388
TI  - Compensatory thrombopoietin production from the liver and bone marrow stimulates
      thrombopoiesis of living rat megakaryocytes in chronic renal failure.
AB  - BACKGROUND/AIMS: Decreased thrombopoiesis has been ascribed a role in the
      pathogenesis of uremic bleeding in chronic renal failure (CRF). However, serum
      thrombopoietin (TPO) levels are usually elevated in CRF patients, suggesting
      increased thrombopoiesis. The aim of this study was to determine the
      thrombopoietic activity in CRF. METHODS: Male Sprague-Dawley rats that underwent
      5/6 nephrectomy were used as the model of CRF. Age-matched sham-operated rats
      were used as controls. Single megakaryocytes were isolated from the rat bone
      marrow, and their size distribution was examined. Megakaryocyte membrane
      invaginations were monitored by confocal imaging of di-8-ANEPPS staining, and
      patch clamp whole-cell recordings of membrane capacitance. TPO gene expression
      was assessed in various tissues. RESULTS: Circulating platelet counts and the
      number of large megakaryocytes were increased in the bone marrow of CRF rats.
      Massive di-8-ANEPPS staining and increased membrane capacitance in large
      megakaryocytes demonstrated increased membrane invaginations. Unaffected Kv1.3
      channel currents per cell surface area demonstrated unaltered channel densities.
      TPO transcription was decreased in the renal cortex but increased in the liver
      and bone marrow of CRF rats. CONCLUSION: Increased thrombopoiesis in CRF was
      thought to be a reactive mechanism to platelet dysfunction. Increased TPO
      production from the liver and bone marrow compensated for decreased production
      from damaged kidneys.

PMID- 22470389
TI  - Prenatal programming of hypertension in the rat: effect of postnatal rearing.
AB  - BACKGROUND/AIMS: Dietary protein deprivation during pregnancy causes hypertension
      in offspring when they become adults. This study examined if postnatal rearing
      had an effect on blood pressure and glomerular number in male rats whose mothers
      were fed either a control diet or a low protein diet. METHODS: Neonates were
      cross fostered at 1 day of age to a different mother. After birth, all nursing
      and weaned rats were fed a control diet. Blood pressure and glomerular number
      were measured in adult offspring. RESULTS: Control rats cross fostered to another
      control mother had a lower blood pressure than low protein rats cross fostered to
      another low protein mother (133 +/- 4 vs. 151 +/- 4 mm Hg, p < 0.05) and a
      greater number of glomeruli (28,388 +/- 989 vs. 25,045 +/- 851, p < 0.05).
      Fostering pups from the 20% group to mothers that were fed a 6% diet during
      pregnancy did not cause hypertension or a reduction in the number of glomeruli.
      However, fostering the 6% group on to mothers that were fed a 20% protein diet
      during pregnancy resulted in normalization of the blood pressure and number of
      glomeruli. CONCLUSION: The hypertension and reduced glomerular number resulting
      from prenatal dietary protein deprivation can be normalized by improving the
      postnatal environment.

PMID- 22470390
TI  - Serum high-sensitivity cardiac troponin T is a significant biomarker of left
      ventricular diastolic dysfunction in subjects with non-diabetic chronic kidney
      disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with left-ventricular (LV)
      diastolic dysfunction (LVDD) which progresses to diastolic heart failure.
      However, biomarkers predicting LVDD in patients with CKD are largely unknown.
      METHODS: In 93 patients with non-diabetic CKD, the relationships among
      echocardiography, high-sensitivity cardiac troponin T (hs-cTnT), B-type
      natriuretic peptide (BNP), and renal function were evaluated. LV mass index, peak
      early diastolic mitral filling velocity (E), peak early diastolic mitral annular
      velocity (E'), and E/E' were recorded. RESULTS: The E' values were significantly
      decreased and E/E', BNP, and hs-cTnT increased with increasing CKD stage. The CKD
      patients with LVDD with E' <5 cm/s had a significantly higher hs-cTnT level as
      well as a significantly higher BNP level compared to those with E' >=5 cm/s. The
      area under the receiver-operating characteristic curve for hs-cTnT and BNP to
      detect E' <5 cm/s was 0.880 (p = 0.0101) and 0.741 (p = 0.0570), respectively. In
      multivariate analysis, hs-cTnT and albuminuria were significantly associated with
      E', and estimated glomerular filtration rate with the hs-cTnT level, after
      adjusting for age, cause of CKD, and other parameters. CONCLUSIONS: These data
      suggest that hs-cTnT may be a useful biomarker of LVDD in non- diabetic CKD
      patients.

PMID- 22470392
TI  - Exploring the Relationships between Hemoglobin, the Endothelium and Vascular
      Health in Patients with Chronic Kidney Disease.
AB  - BACKGROUND/AIMS: The ideal hemoglobin target in chronic kidney disease remains
      unknown. Ultimately, individualized targets may depend upon the properties of the
      patient's endothelial and vascular milieu, and thus the complex relationships
      between these factors need to be further explored. METHODS: Forty-six patients
      with a glomerular filtration rate (GFR) <30 ml/min/1.73 m(2) or on renal
      replacement therapy underwent measurement of hemoglobin, endothelial
      microparticles (EMPs) and aortic pulse wave velocity (PWV) at 0, 3 and 6 months.
      In addition, a number of inflammatory, cardiac and vascular biomarkers were
      measured at baseline. RESULTS: No correlation was observed between baseline
      values of PWV and EMPs, PWV and hemoglobin, or hemoglobin and EMPs in the overall
      cohort. When stratified by CKD status, a positive correlation was observed
      between PWV and EMP CD41-/CD144+ in patients with GFR <30 ml/min/1.73 m(2) only
      (r = 0.54, p = 0.01). Asymmetric dimethylarginine correlated with baseline PWV (r
      = 0.27, p = 0.07), and remained significantly correlated with the 3- and 6-month
      PWV measurement. CONCLUSIONS: In this small heterogeneous cohort of dialysis and
      non-dialysis patients, we were unable to describe a physiologic link between
      anemia, endothelial dysfunction and arterial stiffness.

PMID- 22470391
TI  - Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation
      of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury.
AB  - BACKGROUND/AIMS: It remains elusive whether there is a crosstalk between Smad and
      mitogen-activated protein kinases (MAPKs) and whether it regulates cyclosporine A
      (CyA)-induced apoptosis in renal proximal tubular cells (RPTCs). METHODS: The
      effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western
      blotting or immunofluorescence) and apoptosis (determined by Hoechst 33258
      staining) was examined in HK-2 cells. RESULTS: CyA induced apoptosis at 24 h and
      nuclear translocation of phosphorylated (p)-Smad2/3 at 3 h, which was continued
      till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till
      24 h, and of p-p38MAPK at 1-6 h, which returned to control level at 12 h. CyA did
      not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear
      translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190,
      deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth
      factor (EGF) activated ERK and p38MAPK but not JNK. EGF-induced activation of
      MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis.
      Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on
      CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. CONCLUSION:
      Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates
      apoptosis in CyA-induced RPTC injury.

PMID- 22470393
TI  - Mannitol Reduces the Hydrostatic Pressure in the Proximal Tubule of the Isolated
      Blood-Perfused Rabbit Kidney during Hypoxic Stress and Improves Its Function.
AB  - BACKGROUND/AIMS: Hypoxia may play a role in the development of renal failure in
      donated kidneys. In the present study, the effects of hypoxia on isolated blood
      perfused rabbit kidneys were investigated and the effects of mannitol were
      explored, giving special attention to intratubular pressure. METHODS: Kidneys
      were perfused with their autologous blood during four 30-min periods (P1-P4). P1
      was considered baseline function. In P2, hypoxia was induced either alone or with
      an infusion of mannitol (15 mg/min) during P2-P4. Reoxygenation was applied after
      P2. Proximal intratubular pressure was measured in all conditions. RESULTS:
      During hypoxia, renal blood flow doubled and restored immediately in P3. Urine
      flow stopped in P2, except in the series with mannitol, but gradually resumed in
      P3 and P4. Likewise, creatinine clearance recovered slightly (<25%) in P4, except
      for the series with mannitol, where it still could be measured in P2 and reached
      a value >50% of P1. Proximal intratubular pressure (mean +/- SD) increased from
      12 +/- 5 in P1 to 24 +/- 11 mm Hg during hypoxia and returned to 10 +/- 6 mm Hg
      in P3. This increase was not observed with mannitol. CONCLUSION: Cellular
      swelling might be responsible for the suppressed filtration during hypoxia and
      can be prevented by mannitol.

PMID- 22470394
TI  - Implications of a reduction in the hemoglobin target in erythropoiesis
      stimulating agent-treated hemodialysis patients.
AB  - BACKGROUND: Patients treated with erythropoiesis-stimulating agents (ESAs) to a
      hemoglobin (Hb) level >12.0 g/dl have increased risk of multiple complications,
      including death. The optimal Hb target for ESA use has not been established. We
      hypothesized that reducing the target Hb would prevent levels >12 g/dl and lead
      to significant cost savings. METHODS: Our target Hb range was reduced to 9-11
      g/dl from 10-12 g/dl. Thirty-five chronic hemodialysis (HD) patients received
      erythropoietin (EPO) and intravenous iron from January to December 2009. Data
      analysis included: Hb level, EPO dose, transferrin saturation and ferritin
      levels. EPO was administered via subcutaneous injection weekly or twice weekly.
      RESULTS: The mean monthly Hb level changed from 11.2 to 10.6 g/dl. The
      percentages of patients with mean Hb >10.0, 12.0 and 13.0 g/dl were 82 +/- 6.5,
      10 +/- 5.6 and 1.8 +/- 1.9%, respectively. Weekly EPO dose decreased from 9,500
      to 5,600 units, a 40% reduction per dose per patient and costs. The savings
      exceeded USD 60,000 per year for 35 patients. More than 80% of patients had
      transferrin saturation >20% and ferritin >200 ng/ml throughout the entire period.
      CONCLUSIONS: Lowering the target Hb range to 9-11 g/dl in HD patients achieved
      quality anemia management, avoided values >12.0 g/dl and resulted in cost
      savings. A minimal reduction in quality of life and no change in cardiovascular
      morbidity or mortality would be expected. The study has important implications in
      the new American bundled reimbursement model.

PMID- 22470395
TI  - Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a
      Retrograde Ureteral Approach.
AB  - BACKGROUND/AIMS: Gene therapy involves delivery of exogenous DNA to provide a
      therapeutic protein. Ideally, a gene therapy vector should be non-toxic, non
      immunogenic, easy to produce, and efficient in protecting and delivering DNA into
      target cells. METHODS: Adeno-associated virus (AAV) offers these advantages and
      few, if any, disadvantages, and over 100 isolates exist. We previously showed
      that AAV-mediated gene therapy can be used to restore vision to patients with
      Leber's congenital amaurosis, a disease of childhood blindness. RESULTS: Here we
      show that novel recombinant AAV2/8 and AAV2/9 transduce kidney tubule cells with
      high efficiency both in vitroin cell culture and in vivoin mice. In addition, we
      adapted and modified a retrograde approach to allow for optimal transgene
      delivery to renal tubular cells that further minimizes the risk of an immunogenic
      reaction. CONCLUSIONS: We believe that recombinant AAV2, especially AAV2/8, gene
      delivery to renal tubule cells via a retrograde approach represents a viable
      method for gene therapy for a multitude of renal disorders ranging from autosomal
      dominant polycystic kidney disease to acute kidney injury.

PMID- 22470396
TI  - Acceleration of the meckel syndrome by near-infrared light therapy.
AB  - BACKGROUND/AIMS: Phototherapy using a narrow-band, near-infrared (NIR) light
      (using a light-emitting diode, LED) is being used to treat certain medical
      conditions. This narrow-band red light has been shown to stimulate cytochrome c
      oxidase (CCO) in mitochondria that would stimulate ATP production and has the
      ability to stimulate wound healing. LED treatment also decreases chemical-induced
      oxidative stress in tested systems. As renal cystic diseases are known to have
      evidence of oxidative stress with reduced antioxidant protection, we hypothesized
      that NIR light therapy might ameliorate the renal pathology in renal cystic
      disease. METHODS: Wistar-Wpk/Wpk rats with Meckel syndrome (MKS) were treated
      with light therapy on days 10-18 at which time disease severity was evaluated.
      Wpk rats were either treated daily for 80 s with narrow-band red light (640-690
      nm wavelength) or sham treated. At termination, renal and cerebral pathology was
      evaluated, and renal expression and activity of enzymes were assessed to evaluate
      oxidative stress. Blood was collected for blood urea nitrogen (BUN)
      determination, the left kidney frozen for biochemical evaluation, and the right
      kidney and head fixed for morphological evaluation. RESULTS: There were no
      significant effects of LED treatment on body weight (BW) or total kidney weight
      in non-cystic rats. Total kidney weight was increased and anephric BW was
      decreased in cystic versus non-cystic controls. LED reduced BW and total kidney
      weight in cystic rats compared to non-light-treated cystic (control) rats. BUN
      was already increased almost 6-fold in cystic rats compared to control rats. BUN
      was further increased almost 2-fold with NIR treatment in both non-cystic and
      cystic rats compared to cystic and control rats. The hydrocephalus associated
      with Wpk/Wpk (ventricular volume expressed as total volume and as percent of
      anephric BW) was also more severe in NIR-treated cystic rats compared to the
      normal control rats. Renal glutathione peroxidase and catalase (CAT) were reduced
      in the cystic kidney while superoxide dismutase and CCO were increased. NIR
      increased CAT and CCO, marginally decreased glutathione S-transferase and
      slightly decreased glutathione reductase in cystic rats compared to the normal
      control rats. The detrimental effects of NIR may be related to reduced renal
      blood flow associated with progression of cystic pathology. Compression by cysts
      may not allow sufficient oxygen or nutrient supply necessary to support the
      increased oxidative phosphorylation-associated cellular activity, and the
      increased demand induced by NIR-increased CCO may have created further oxidative
      stress. CONCLUSION: LED phototherapy initiated after the onset of symptoms was
      detrimental to MKS-induced pathology. NIR stimulates CCO thereby increasing the
      kidney's need for oxygen. We hypothesize that cystic compression of the
      vasculature impairs oxygen availability and the enhanced CCO activity produces
      more radicals, which are not sufficiently detoxified by the increased CAT
      activity.

PMID- 22470397
TI  - Comparison of estimated protein output and urine protein: creatinine ratio in
      first and second voids with 24-hour urine protein.
AB  - BACKGROUND: Current UK guidelines for the identification, management and referral
      of chronic kidney disease advise an early-morning urine sample for the
      albumin:creatinine ratio or the protein:creatinine ratio (PCR) in order to
      quantify proteinuria. Estimated protein output (EPO) is an alternative and
      possibly better method of quantifying proteinuria which takes lean weight into
      consideration. METHODS: We carried out a single-centre study of 36 adult patients
      with proteinuric nephropathy over a period of 18 months. Urinary PCR and EPO
      estimates of 24-hour urine protein were compared with 24-hour urine collections
      by Bland-Altman analysis. RESULTS: Average 24-hour urine protein was 1.6 g (range
      0.2-5.1 g). Best agreement with 24-hour protein was for first-void EPO (limits of
      agreement 0.33-1.59) followed by a second-void EPO (0.40-1.76), then second-void
      PCR (0.40-2.08) and lastly first-void PCR (0.28-2.03). None of the differences
      between estimates of urine protein excretion and 24-hour urine protein were
      statistically significant. All estimates of protein output had wide confidence
      intervals confirming that spot urine samples, while simple and convenient to do,
      are imprecise measures of 24-hour urine protein excretion. CONCLUSION: When
      estimating 24-hour urine protein from a spot urine sample, EPO may be marginally
      more accurate than PCR, and first-void urine samples slightly better than second
      void urine samples, but a first- or second-void PCR will suffice in most
      instances.

PMID- 22470398
TI  - Plasma S100A12 levels and peripheral arterial disease in end-stage renal disease.
AB  - BACKGROUND: S100A12 is an endogenous ligand of the receptor for advanced
      glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal
      disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral
      arterial disease (PAD) is common in HD patients and is associated with increased
      cardiovascular morbidity and mortality rates in this population. To date,
      however, no study has specifically assessed the relationship between plasma
      S100A12 and PAD in HD patients. METHODS: We conducted a cross-sectional study of
      152 HD patients in our affiliated hospital. We investigated PAD history and
      patient characteristics and quantified plasma S100A12 levels in all participants.
      RESULTS: HD patients with PAD (n = 26; 21.9 [13.6-33.4] ng/ml) showed
      significantly higher plasma S100A12 levels than HD patients without PAD (n = 126;
      11.8 [7.5-17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis,
      the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29
      25.3; p = 0.022) was identified as an independent factor associated with PAD
      prevalence. Another factor associated with PAD prevalence was the ankle-brachial
      index (OR 0.54; 95% CI 0.40-0.74; p < 0.001). CONCLUSION: These results suggest
      that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD
      patients undergoing HD.

PMID- 22470399
TI  - Rituximab treatment for membranous nephropathy: a French clinical and serological
      retrospective study of 28 patients.
AB  - The development of well-tolerated and effective therapies that target the
      pathogenesis of membranous nephropathy (MN) would be useful. Our objective was to
      evaluate the efficacy of rituximab in MN. We analyzed the outcome of 28 patients
      treated with rituximab for idiopathic MN. Anti-PLA(2)R antibodies in serum and
      PLA(2)R antigen in kidney biopsy were assessed in 10 and 9 patients,
      respectively. Proteinuria was significantly decreased by 56, 62 and 87% at 3, 6
      and 12 months, respectively. At 6 months, 2 patients achieved complete remission
      (CR) and 12 partial remission (PR; overall renal response, 50%). At 12 months (n
      = 23), CR was achieved in 6 patients and PR in 13 patients (overall renal
      response, 82.6%). Three patients suffered a relapse of nephrotic proteinuria 27
      50 months after treatment. Univariate analysis suggested that the degree of renal
      failure (MDRD estimated glomerular filtration rate <45/ml/min/1.73 m(2)) is an
      independent factor that predicts lack of response to rituximab. Anti-PLA(2)R
      antibodies were detected in the serum of 10 patients, and PLA(2)R antigen in
      immune deposits in 8 of 9 patients. Antibodies became negative in all 5
      responsive patients with available follow-up sera. In this retrospective study, a
      high rate of remission was achieved 12 months after treatment.

PMID- 22470401
TI  - Noble gas (argon and xenon)-saturated cold storage solutions reduce ischemia
      reperfusion injury in a rat model of renal transplantation.
AB  - BACKGROUND: Following kidney transplantation, ischemia-reperfusion injury
      contributes to adverse outcomes. The purpose of this study was to determine
      whether a cold-storage solution saturated with noble gas (xenon or argon) could
      limit ischemia-reperfusion injury following cold ischemia. METHODS: Sixty Wistar
      rats were randomly allocated to 4 experimental groups. Kidneys were harvested and
      then stored for 6 h before transplantation in cold-storage solution (Celsior(r))
      saturated with either air, nitrogen, xenon or argon. A syngenic orthotopic
      transplantation was performed. Renal function was determined on days 7 and 14
      after transplantation. Transplanted kidneys were removed on day 14 for
      histological and immunohistochemical analyses. RESULTS: Creatinine clearance was
      significantly higher and urinary albumin significantly lower in the argon and
      xenon groups than in the other groups at days 7 and 14. These effects were
      considerably more pronounced for argon than for xenon. In addition, kidneys
      stored with argon, and to a lesser extent those stored with xenon, displayed
      preserved renal architecture as well as higher CD-10 and little active caspase-3
      expression compared to other groups. CONCLUSION: Argon- or xenon-satured cold
      storage solution preserved renal architecture and function following
      transplantation by reducing ischemia-reperfusion injury.

PMID- 22470400
TI  - Identifying depression in South asian patients with end-stage renal disease:
      considerations for practice.
AB  - Depression is a prevalent burden for patients with end-stage renal disease (ESRD)
      and one that is under-recognized and consequently under-treated. Although several
      studies have explored the association between depression symptoms, treatment
      adherence and outcomes in Euro-American patient groups, quantitative and
      qualitative exploration of these issues in patients from different cultural and
      ethnic backgrounds has been lacking. This review discusses the methodological
      issues associated with measuring depression in patients of South Asian origin who
      have a 3- to 5-fold greater risk of developing ESRD. There is a need to advance
      research into the development of accurate screening practices for this patient
      group, with an emphasis on studies utilizing rigorous approaches to evaluating
      the use of both emic (culture-specific) and etic (universal or culture-general)
      screening instruments.

PMID- 22470402
TI  - Serum alkaline phosphatase levels and left ventricular diastolic dysfunction in
      patients with advanced chronic kidney disease.
AB  - BACKGROUND: High levels of alkaline phosphatase (ALP) have been associated with
      increased mortality in patients with advanced chronic kidney disease (CKD). We
      hypothesize that elevated ALP could be partly explained by subclinical liver
      congestion related to left ventricular diastolic dysfunction. METHODS: Doppler
      echocardiography was performed in 68 patients with advanced CKD followed up for a
      median of 2.1 years. Time-averaged levels of ALP and gamma-glutamyl transferase
      (GGT) were compared between patients with and without diastolic dysfunction. We
      also evaluated the effect of intensifying diuretic treatment on ALP levels in a
      small group of 16 patients with high ALP and signs of volume overload. RESULTS:
      ALP correlated significantly (p < 0.001) with GGT but not with parathyroid
      hormone (p = 0.09). Patients with diastolic dysfunction showed higher ALP (p =
      0.01), higher GGT (p = 0.03) and lower albumin (p = 0.04). The highest values of
      ALP were observed in patients with diastolic dysfunction plus pulmonary
      hypertension (p = 0.01). Intensifying diuretic therapy in a subgroup of patients
      with signs of fluid overload induced a significant reduction in body weight, GGT
      (p < 0.001) and ALP levels (p < 0.001). CONCLUSIONS: Elevated ALP in patients
      with advanced CKD could be partly explained by subclinical liver congestion
      related to left ventricular diastolic dysfunction, hypervolemia or both. The
      worse prognosis of these patients could be explained by their myocardial damage.

PMID- 22470403
TI  - Effect of inflammation on the relationship of pulse pressure and mortality in
      haemodialysis.
AB  - BACKGROUND/AIM: The effect of hypertension on mortality in haemodialysis patients
      is controversial and can be confounded by non-traditional risk factors like
      systemic inflammation. This study examined the effect of systolic blood pressure
      (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) on mortality in
      haemodialysis patients, separately with and without markers of systemic
      inflammation. METHODS: Data from the United States Renal Data System were
      analysed for 9,862 patients receiving haemodialysis on December 31, 1993,
      followed through May 2005. RESULTS: In Cox regression analysis, increased age,
      diabetes, low albumin, high white blood count, low cholesterol, low haemoglobin,
      high phosphate, low DBP, and cardiovascular comorbidity were associated with high
      mortality, but SBP was not. Elevated PP adjusted for SBP, age, diabetes,
      haemoglobin, albumin, cholesterol, calcium, phosphate, parathyroid hormone, and
      white blood count was associated with higher mortality [adjusted hazard ratio, PP
      1.006 (95% confidence interval, CI, 1.002-1.010); SBP 0.993 (95% CI 0.990
      0.996)]. In dual models, PP adjusted for SBP then DBP was associated with higher
      mortality [PP 1.029 (95% CI 1.027-1.032); SBP 0.981 (95% CI 0.979-0.983); PP
      1.010 (95% CI 1.008-1.011); DBP 0.981 (95% CI 0.979-0.983)]. Increasing PP
      deciles >70 mm Hg were associated with increasing mortality in the absence of
      markers of systemic inflammation (white blood count >10 * 10(9)/l, albumin <3.5
      g/dl, diabetes), but not in their presence. CONCLUSION: PP was a better indicator
      of adverse outcome than DBP or SBP. Inflammation-associated injury may mask the
      effect of PP on mortality in haemodialysis patients.

PMID- 22470404
TI  - No Evidence for a Parent-of-Origin Specific Differentially Methylated Region
      Linked to RASGRF1.
AB  - Imprinted genes are expressed from one parental allele in a parent-of-origin
      manner. This monoallelic behavior is regulated by allele-specific DNA methylation
      that is confined to differentially methylated regions (DMRs). To date there are
      over 80 known human imprinted genes of which only three are known to have
      paternally methylated DMRs. In mice there exists an additional paternally
      methylated DMR associated with Rasgrf1. The Rasgrf1 gene forms part of the MAPK
      signaling pathway and plays a role in long-term memory formation and growth
      control. A RASGRF1-associated parent-of-origin specific DMR in humans and its
      methylation status in sperm DNA have not been explored. The primary aim of this
      study was to determine whether the human RASGRF1 gene contains a DMR and whether
      this DMR is paternally methylated and shows roughly 50% methylation in somatic
      tissue. Computational assessments were done to identify putative CTCF binding
      sites, CpG islands (CGIs) that could serve as potential RASGRF1 DMRs and tandem
      repeats within or adjacent to these CGIs. The methylation status of three
      putative CGIs was assessed using quantitative pyrosequencing technology. None of
      the putative CTCF binding sites was found to occur in the predicted CGIs. The
      three putative CGIs linked to RASGRF1 did not display allele-specific
      methylation. While one of the three CGIs was found to be hypomethylated in both
      blood DNA and sperm DNA, the other two were found to be hypermethylated. The CGIs
      evaluated in this study did not fit the criteria of being a allele-specific DMR.
      Unlike the mouse Rasgrf1 locus, the human RASGRF1-associated CpG rich regions do
      not exhibit differential methylation in a parent-of-origin manner.

PMID- 22470405
TI  - Regulation of miRNA 219 and miRNA Clusters 338 and 17-92 in Oligodendrocytes.
AB  - MicroRNAs (miRs) regulate diverse molecular and cellular processes including
      oligodendrocyte (OL) precursor cell (OPC) proliferation and differentiation in
      rodents. However, the role of miRs in human OPCs is poorly understood. To
      identify miRs that may regulate these processes in humans, we isolated OL lineage
      cells from human white matter and analyzed their miR profile. Using endpoint RT
      PCR assays and quantitative real-time PCR, we demonstrate that miR-219, miR-338,
      and miR-17-92 are enriched in human white matter and expressed in acutely
      isolated human OLs. In addition, we report the expression of closely related miRs
      (miR-219-1-3p, miR-219-2-3p, miR-1250, miR-657, miR-3065-5p, miR-3065-3p) in both
      rodent and human OLs. Our findings demonstrate that miRs implicated in rodent OPC
      proliferation and differentiation are regulated in human OLs and may regulate
      myelination program in humans. Thus, these miRs should be recognized as potential
      therapeutic targets in demyelinating disorders.

PMID- 22470406
TI  - Pathological gambling: prevalence, diagnosis, comorbidity, and intervention in
      Germany.
AB  - BACKGROUND: The number of pathological gamblers seeking treatment has risen
      continuously till the present, and the trend shows no sign of reversal. Estimates
      of the number of pathological gamblers in Germany range from 103,000 to 290,000,
      corresponding to 0.2% to 0.6% of the population. Pathological gambling often
      accompanies other mental disturbances. Doctors who learn that their patients
      suffer from such disturbances should ask targeted questions about gambling
      behavior to increase the chance that this problem will be detected early on.
      METHODS: This article is based on an analysis of secondary data obtained from the
      German Statutory Pension Insurance Scheme and the Federal Statistical Office and
      on a selective review of the literature on comorbidities and available
      interventions. RESULTS: The rate of inpatient treatment for pathological gambling
      tripled from 2000 to 2010. Most pathological gamblers are men (70%-80%). More
      than 90% of the patients suffer from more than one mental disturbance; 40% of
      them carry five different psychiatric diagnoses. Simple screening instruments for
      pathological gambling are easy to use in routine practice and facilitate the
      diagnosis. CONCLUSION: As with alcoholics, only a small fraction of pathological
      gamblers receives the appropriate support and treatment. Educational seminars to
      raise awareness among physicians and targeted measures for early detection might
      result in more of the affected persons getting suitable help.

PMID- 22470407
TI  - The diagnosis and treatment of minimal hepatic encephalopathy.
AB  - BACKGROUND: The subtype of hepatic encephalopathy (HE) called minimal hepatic
      encephalopathy (MHE) is highly prevalent (22-74%) among patients with liver
      dysfunction. MEH is defined as HE without grossly evident neurologic
      abnormalities, but with cognitive deficits that can be revealed by psychometric
      testing. METHODS: This article is based on relevant original publications and
      reviews in English and German (1970-2011) that were retrieved by a selective key
      word-based search in the Medline and PubMed databases. RESULTS: Despite its mild
      manifestations, MHE impairs patients' quality of life and their ability to work.
      It impairs driving ability and is associated with a higher rate of motor vehicle
      accidents. Furthermore, patients with MHE fall more often and are more likely to
      undergo progression to overt HE. The main pathophysiological mechanism of MHE is
      hyperammonemia leading to astrocyte dysfunction. Psychometric tests are the
      standard instruments for establishing the diagnosis; further, supportive
      diagnostic tools include neurophysiological tests and imaging studies. Recent
      randomized and controlled trials have revealed that treatment with lactulose or
      rifaximin therapy improves the quality of life of patients with MHE. Rifaximin
      was also found to improve driving performance in a simulator. A combination of
      these two drugs prevents the recurrence of episodic HE over a 6-months follow-up
      period. Moreover, small-scale trials have revealed that some dietary supplements
      can improve the cognitive deficits of MHE. CONCLUSION: Clinical trials have shown
      that patients with MHE and patients who have had an episode of overt HE in the
      past can benefit from drug treatment.

PMID- 22470408
TI  - Correspondence (letter to the editor): Laboratory tests to ascertain tumor
      resistance to drugs are available.

PMID- 22470410
TI  - Correspondence (letter to the editor): New recommendations.

PMID- 22470411
TI  - Simulation of anterior cruciate ligament deficiency in a musculoskeletal model
      with anatomical knees.
AB  - Abnormal knee kinematics and meniscus injury resulting from anterior cruciate
      ligament (ACL) deficiency are often implicated in joint degeneration even though
      changes in tibio-femoral contact location after injury are small, typically only
      a few millimeters. Ligament reconstruction surgery does not significantly reduce
      the incidence of early onset osteoarthritis. Increased knowledge of knee contact
      mechanics would increase our understanding of the effects of ACL injury and help
      guide ACL reconstruction methods. Presented here is a cadaver specific
      computational knee model combined with a body-level musculoskeletal model from a
      subject of similar height and weight as the cadaver donor. The knee model was
      developed in the multi-body framework and includes representation of the menisci.
      Experimental body-level measurements provided input to the musculoskeletal model.
      The location of tibio-menisco-femoral contact as well as contact pressures were
      compared for models with an intact ACL, partial ACL transection (posterolateral
      bundle transection), and full ACL transection during a muscle driven forward
      dynamics simulation of a dual limb squat. During the squat, small changes in
      femur motion relative to the tibia for both partial and full ACL transection push
      the lateral meniscus in the posterior direction at extension. The central
      anterior region of the lateral meniscus then becomes "wedged" between the tibia
      and femur during knee flexion. This "wedging" effect does not occur for the
      intact knee. Peak contact pressure and contact locations are similar for the
      partial tear and complete ACL transection during the deep flexion portion of the
      squat, particularly on the lateral side. The tibio-femoral contact location on
      the tibia plateau shifts slightly to the posterior and lateral direction with ACL
      transection.

PMID- 22470412
TI  - Carpal tunnel syndrome: a review of the recent literature.
AB  - Carpal Tunnel Syndrome (CTS) remains a puzzling and disabling condition present
      in 3.8% of the general population. CTS is the most well-known and frequent form
      of median nerve entrapment, and accounts for 90% of all entrapment neuropathies.
      This review aims to provide an overview of this common condition, with an
      emphasis on the pathophysiology involved in CTS. The clinical presentation and
      risk factors associated with CTS are discussed in this paper. Also, the various
      methods of diagnosis are explored; including nerve conduction studies,
      ultrasound, and magnetic resonance imaging.

PMID- 22470414
TI  - The monkey puzzle: a systematic review of studies of stress, social hierarchies,
      and heart disease in monkeys.
AB  - BACKGROUND: It is often suggested that psychosocial factors, such as stress, or
      one's social position, may play an important role in producing social gradients
      in human disease. Evidence in favour of this model of health inequalities has
      relied, in part, on studies of the health effects of the natural social
      hierarchies found among non-human primates. This study aimed to assess the
      strength of this evidence. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review
      was carried out to identify all studies of psychosocial factors and coronary
      artery disease (CAD) in non-human primates. We searched databases (MEDLINE,
      PsycInfo, EMBASE, and Primatelit from inception to November 2010) to identify
      experimental and observational studies of the impact of social reorganisation,
      social instability, and disruption of dominance hierarchies on primate CAD
      outcomes. We also handsearched bibliographies and examined the citations to those
      studies in public health articles. Fourteen studies were found which presented
      evidence on CAD and social status and/or psychosocial stress. These suggested
      that the association between social status and disease may be sex-specific: in
      female monkeys dominant status may be protective, with subordinate females having
      a greater extent of atherosclerosis. In male monkeys the reverse may be the case.
      CONCLUSIONS/SIGNIFICANCE: Overall, non-human primate studies present only limited
      evidence for an association between social status and CAD, Despite this, there is
      selective citation of individual non-human primate studies in reviews and
      commentaries relating to human disease aetiology. Such generalisation of data
      from monkey studies to human societies does not appear warranted.

PMID- 22470415
TI  - The SpikerBox: a low cost, open-source bioamplifier for increasing public
      participation in neuroscience inquiry.
AB  - Although people are generally interested in how the brain functions, neuroscience
      education for the public is hampered by a lack of low cost and engaging teaching
      materials. To address this, we developed an open-source tool, the SpikerBox,
      which is appropriate for use in middle/high school educational programs and by
      amateurs. This device can be used in easy experiments in which students insert
      sewing pins into the leg of a cockroach, or other invertebrate, to amplify and
      listen to the electrical activity of neurons. With the cockroach leg preparation,
      students can hear and see (using a smartphone oscilloscope app we have developed)
      the dramatic changes in activity caused by touching the mechanosensitive barbs.
      Students can also experiment with other manipulations such as temperature, drugs,
      and microstimulation that affect the neural activity. We include teaching guides
      and other resources in the supplemental materials. These hands-on lessons with
      the SpikerBox have proven to be effective in teaching basic neuroscience.

PMID- 22470416
TI  - Massive consumption of gelatinous plankton by Mediterranean apex predators.
AB  - Stable isotopes of carbon and nitrogen were used to test the hypothesis that
      stomach content analysis has systematically overlooked the consumption of
      gelatinous zooplankton by pelagic mesopredators and apex predators. The results
      strongly supported a major role of gelatinous plankton in the diet of bluefin
      tuna (Thunnus thynnus), little tunny (Euthynnus alletteratus), spearfish
      (Tetrapturus belone) and swordfish (Xiphias gladius). Loggerhead sea turtles
      (Caretta caretta) in the oceanic stage and ocean sunfish (Mola mola) also
      primarily relied on gelatinous zooplankton. In contrast, stable isotope ratios
      ruled out any relevant consumption of gelatinous plankton by bluefish (Pomatomus
      saltatrix), blue shark (Prionace glauca), leerfish (Lichia amia), bonito (Sarda
      sarda), striped dolphin (Stenella caerueloalba) and loggerhead sea turtles
      (Caretta caretta) in the neritic stage, all of which primarily relied on fish and
      squid. Fin whales (Balaenoptera physalus) were confirmed as crustacean consumers.
      The ratios of stable isotopes in albacore (Thunnus alalunga), amberjack (Seriola
      dumerili), blue butterfish (Stromaeus fiatola), bullet tuna (Auxis rochei),
      dolphinfish (Coryphaena hyppurus), horse mackerel (Trachurus trachurus), mackerel
      (Scomber scombrus) and pompano (Trachinotus ovatus) were consistent with mixed
      diets revealed by stomach content analysis, including nekton and crustaceans, but
      the consumption of gelatinous plankton could not be ruled out completely. In
      conclusion, the jellyvorous guild in the Mediterranean integrates two specialists
      (ocean sunfish and loggerhead sea turtles in the oceanic stage) and several
      opportunists (bluefin tuna, little tunny, spearfish, swordfish and, perhaps, blue
      butterfish), most of them with shrinking populations due to overfishing.

PMID- 22470417
TI  - Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.
AB  - Hepatitis B virus (HBV) produces high quantities of subviral surface antigen
      particles (HBsAg) which circulate in the blood outnumbering virions of about
      1?10(3-6) times. In individuals coinfected with the defective hepatitis Delta
      virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as
      ribonucleoprotein complexes within HBsAg subviral particles. We addressed the
      question whether subviral HBsAg particles may carry in the same way cellular
      microRNAs (miRNAs) which are released into the bloodstream within different
      subcellular forms such as exosomes and microvescicles. Circulating HBsAg
      particles were isolated from sera of 11 HBsAg carriers by selective
      immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and
      human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty
      nine human miRNAs were found to be significantly associated with the
      immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non
      parametric tests (Mann-Whitney, p<0.05) with respect to controls. Moreover
      immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed
      in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most
      frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145) as well as immune
      regulatory (most frequent = miR-106b and miR-223). Computationally predicted
      target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing
      with host-pathogen. The finding that HBsAg particles carry selective pools of
      hepatocellular miRNAs opens new avenues of research to disentangle the complex
      interactions between host and HBV and provides a non invasive tool to study the
      physiopathology of liver epigenetics.

PMID- 22470418
TI  - MicroRNA expression analysis in the cellulosic biofuel crop switchgrass (Panicum
      virgatum) under abiotic stress.
AB  - Switchgrass has increasingly been recognized as a dedicated biofuel crop for its
      broad adaptation to marginal lands and high biomass. However, little is known
      about the basic biology and the regulatory mechanisms of gene expression in
      switchgrass, particularly under stress conditions. In this study, we investigated
      the effect of salt and drought stress on switchgrass germination, growth and the
      expression of small regulatory RNAs. The results indicate that salt stress had a
      gradual but significant negative effect on switchgrass growth and development.
      The germination rate was significantly decreased from 82% for control to 36%
      under 1% NaCl treatment. However, drought stress had little effect on the
      germination rate but had a significant effect on the growth of switchgrass under
      the severest salinity stress. Both salt and drought stresses altered the
      expression pattern of miRNAs in a dose-dependent manner. However, each miRNA
      responded to drought stress in a different pattern. Salt and drought stress
      changed the expression level of miRNAs mainly from 0.9-fold up-regulation to 0.7
      fold down-regulation. miRNAs were less sensitive to drought treatment than
      salinity treatment, as evidenced by the narrow fold change in expression levels.
      Although the range of change in expression level of miRNAs was similar under salt
      and drought stress, no miRNAs displayed significant change in expression level
      under all tested salt conditions. Two miRNAs, miR156 and miR162, showed
      significantly change in expression level under high drought stress. This suggests
      that miR156 and miR162 may attribute to the adaption of switchgrass to drought
      stress and are good candidates for improving switchgrass as a biofuel crop by
      transgenic technology.

PMID- 22470419
TI  - Beneficial metabolic effects of 2',3',5'-tri-acetyl-N6- (3-hydroxylaniline)
      adenosine in the liver and plasma of hyperlipidemic hamsters.
AB  - BACKGROUND: Pharmaceutical research of hyperlipidemia has been commonly pursued
      using traditional approaches. However, unbiased metabonomics attempts to explore
      the metabolic signature of hyperlipidemia in a high-throughput manner to
      understand pathophysiology of the disease process. METHODOLOGY/PRINCIPAL
      FINDINGS: As a new way, we performed (1)H NMR-based metabonomics to evaluate the
      beneficial effects of 2',3',5'-tri-acetyl-N(6)- (3-hydroxylaniline) adenosine
      (WS070117) on plasma and liver from hyperlipidemic Syrian golden hamsters. Both
      plasma and liver profiles provided a clearer distinction between the control and
      hyperlipidemic hamsters. Compared to control animals, hyperlipidemic hamsters
      showed a higher content of lipids (triglyceride and cholesterol), lactate and
      alanine together with a lower content of choline-containing compounds (e.g.,
      phosphocholine, phosphatidylcholine, and glycerophosphocholine) and betaine. As a
      result, metabonomics-based findings such as the PCA and OPLS-DA plotting of
      metabolic state and analysis of potential biomarkers in plasma and liver
      correlated well to the assessment of biochemical assays, Oil Red O staining and
      in vivo ultrasonographic imaging suggesting that WS070117 was able to regulate
      lipid content and displayed more beneficial effects on plasma and liver than
      simvastatin. CONCLUSIONS/SIGNIFICANCE: This work demonstrates the promise of
      applying (1)H NMR metabonomics to evaluate the beneficial effects of WS070117
      which may be a good drug candidate for hyperlipidemia.

PMID- 22470420
TI  - Improved detection of bifidobacteria with optimised 16S rRNA-gene based
      pyrosequencing.
AB  - The 16S rRNA gene is conserved across all bacteria and as such is routinely
      targeted in PCR surveys of bacterial diversity. PCR primer design aims to amplify
      as many different 16S rRNA gene sequences from as wide a range of organisms as
      possible, though there are no suitable 100% conserved regions of the gene,
      leading to bias. In the gastrointestinal tract, bifidobacteria are a key genus,
      but are often under-represented in 16S rRNA surveys of diversity. We have
      designed modified, 'bifidobacteria-optimised' universal primers, which we have
      demonstrated detection of bifidobacterial sequence present in DNA mixtures at 2%
      abundance, the lowest proportion tested. Optimisation did not compromise the
      detection of other organisms in infant faecal samples. Separate validation using
      fluorescence in situ hybridisation (FISH) shows that the proportions of
      bifidobacteria detected in faecal samples were in agreement with those obtained
      using 16S rRNA based pyrosequencing. For future studies looking at faecal
      microbiota, careful selection of primers will be key in order to ensure effective
      detection of bifidobacteria.

PMID- 22470421
TI  - Characterization of an Nmr homolog that modulates GATA factor-mediated nitrogen
      metabolite repression in Cryptococcus neoformans.
AB  - Nitrogen source utilization plays a critical role in fungal development,
      secondary metabolite production and pathogenesis. In both the Ascomycota and
      Basidiomycota, GATA transcription factors globally activate the expression of
      catabolic enzyme-encoding genes required to degrade complex nitrogenous
      compounds. However, in the presence of preferred nitrogen sources such as
      ammonium, GATA factor activity is inhibited in some species through interaction
      with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite
      repression, enables preferential utilization of readily assimilated nitrogen
      sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor
      Gat1/Are1 has been co-opted into regulating multiple key virulence traits in
      addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function
      and investigate the regulatory role of the predicted Nmr homolog Tar1. While
      GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is
      unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate
      derepression of non-preferred nitrogen catabolic pathways in the simultaneous
      presence of favoured sources. In addition to exhibiting its evolutionary
      conserved role of inhibiting GATA factor activity under repressing conditions,
      Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing
      conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite
      repression, however, remains open to speculation. Interaction between Tar1 and
      Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and
      Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr
      proteins and GATA factors that are known to interact with each other.
      Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence,
      reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis.

PMID- 22470422
TI  - A genome-wide identification analysis of small regulatory RNAs in Mycobacterium
      tuberculosis by RNA-Seq and conservation analysis.
AB  - We propose a new method for smallRNAs (sRNAs) identification. First we build an
      effective target genome (ETG) by means of a strand-specific procedure. Then we
      propose a new bioinformatic pipeline based mainly on the combination of two types
      of information: the first provides an expression map based on RNA-seq data (Reads
      Map) and the second applies principles of comparative genomics leading to a
      Conservation Map. By superimposing these two maps, a robust method for the search
      of sRNAs is obtained. We apply this methodology to investigate sRNAs in
      Mycobacterium tuberculosis H37Rv. This bioinformatic procedure leads to a total
      list of 1948 candidate sRNAs. The size of the candidate list is strictly related
      to the aim of the study and to the technology used during the verification
      process. We provide performance measures of the algorithm in identifying
      annotated sRNAs reported in three recent published studies.

PMID- 22470423
TI  - Effects of trophic level and metamorphosis on discrimination of hydrogen isotopes
      in a plant-herbivore system.
AB  - The use of stable isotopes in ecological studies requires that we know the
      magnitude of discrimination factors between consumer and element sources. The
      causes of variation in discrimination factors for carbon and nitrogen have been
      relatively well studied. In contrast, the discrimination factors for hydrogen
      have rarely been measured. We grew cabbage looper caterpillars (Trichoplusia ni)
      on cabbage (Brassica oleracea) plants irrigated with four treatments of deuterium
      enriched water (deltaD = -131, -88, -48, and -20/00, respectively), allowing some
      of them to reach adulthood as moths. Tissue deltaD values of plants,
      caterpillars, and moths were linearly correlated with the isotopic composition of
      irrigation water. However, the slope of these relationships was less than 1, and
      hence, discrimination factors depended on the deltaD value of irrigation water.
      We hypothesize that this dependence is an artifact of growing plants in an
      environment with a common atmospheric deltaD value. Both caterpillars and moths
      were significantly enriched in deuterium relative to plants by ~450/00 and 230/00
      respectively, but the moths had lower tissue to plant discrimination factors than
      did the caterpillars. If the trophic enrichment documented here is universal,
      deltaD values must be accounted for in geographic assignment studies. The
      isotopic value of carbon was transferred more or less faithfully across trophic
      levels, but delta(15)N values increased from plants to insects and we observed
      significant non-trophic (15)N enrichment in the metamorphosis from larvae to
      adult.

PMID- 22470424
TI  - A high-density genome-wide association screen of sporadic ALS in US veterans.
AB  - Following reports of an increased incidence of amyotrophic lateral sclerosis
      (ALS) in U.S. veterans, we have conducted a high-density genome-wide association
      study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We
      tested ~1.3 million single nucleotide polymorphisms (SNPs) for association with
      ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or
      probable ALS and 348 Caucasian veteran controls. To increase power, we also
      included genotypes from 5909 publicly-available non-veteran controls in the
      analysis. In the survival analysis, we tested for association between SNPs and
      post-diagnosis survival time in 639 Caucasian veteran cases with definite or
      probable ALS. After this discovery phase, we performed follow-up genotyping of
      299 SNPs in an independent replication sample of Caucasian veterans and non
      veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although
      no SNPs reached genome-wide significance in the discovery phase for either
      phenotype, three SNPs were statistically significant in the replication analysis
      of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and
      rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were
      implicated by previous GWA studies of ALS were marginally significant in the
      pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p =
      4.4*10(-4)) and rs6985069 near ELP3 (p = 4.8*10(-4)). Our results underscore the
      difficulty of identifying and convincingly replicating genetic associations with
      a rare and genetically heterogeneous disorder such as ALS, and suggest that
      common SNPs are unlikely to account for a substantial proportion of patients
      affected by this devastating disorder.

PMID- 22470425
TI  - Enhanced visual temporal resolution in autism spectrum disorders.
AB  - Cognitive functions that rely on accurate sequencing of events, such as action
      planning and execution, verbal and nonverbal communication, and social
      interaction rely on well-tuned coding of temporal event-structure. Visual
      temporal event-structure coding was tested in 17 high-functioning adolescents and
      adults with autism spectrum disorder (ASD) and mental- and chronological-age
      matched typically-developing (TD) individuals using a perceptual simultaneity
      paradigm. Visual simultaneity thresholds were lower in individuals with ASD
      compared to TD individuals, suggesting that autism may be characterised by
      increased parsing of temporal event-structure, with a decreased capability for
      integration over time. Lower perceptual simultaneity thresholds in ASD were also
      related to increased developmental communication difficulties. These results are
      linked to detail-focussed and local processing bias.

PMID- 22470427
TI  - Molecular and antigenic characterization of reassortant H3N2 viruses from turkeys
      with a unique constellation of pandemic H1N1 internal genes.
AB  - Triple reassortant (TR) H3N2 influenza viruses cause varying degrees of loss in
      egg production in breeder turkeys. In this study we characterized TR H3N2 viruses
      isolated from three breeder turkey farms diagnosed with a drop in egg production.
      The eight gene segments of the virus isolated from the first case submission (FAV
      003) were all of TR H3N2 lineage. However, viruses from the two subsequent case
      submissions (FAV-009 and FAV-010) were unique reassortants with PB2, PA,
      nucleoprotein (NP) and matrix (M) gene segments from 2009 pandemic H1N1 and the
      remaining gene segments from TR H3N2. Phylogenetic analysis of the HA and NA
      genes placed the 3 virus isolates in 2 separate clades within cluster IV of TR
      H3N2 viruses. Birds from the latter two affected farms had been vaccinated with a
      H3N4 oil emulsion vaccine prior to the outbreak. The HAl subunit of the H3N4
      vaccine strain had only a predicted amino acid identity of 79% with the isolate
      from FAV-003 and 80% for the isolates from FAV-009 and FAV-0010. By comparison,
      the predicted amino acid sequence identity between a prototype TR H3N2 cluster IV
      virus A/Sw/ON/33853/2005 and the three turkey isolates from this study was 95%
      while the identity between FAV-003 and FAV-009/10 isolates was 91%. When the
      previously identified antigenic sites A, B, C, D and E of HA1 were examined,
      isolates from FAV-003 and FAV-009/10 had a total of 19 and 16 amino acid
      substitutions respectively when compared with the H3N4 vaccine strain. These
      changes corresponded with the failure of the sera collected from turkeys that
      received this vaccine to neutralize any of the above three isolates in vitro.

PMID- 22470426
TI  - Genetic variability of human respiratory syncytial virus A strains circulating in
      Ontario: a novel genotype with a 72 nucleotide G gene duplication.
AB  - Human respiratory syncytial virus (HRSV) is the main cause of acute lower
      respiratory infections in children under 2 years of age and causes repeated
      infections throughout life. We investigated the genetic variability of RSV-A
      circulating in Ontario during 2010-2011 winter season by sequencing and
      phylogenetic analysis of the G glycoprotein gene.Among the 201 consecutive RSV
      isolates studied, RSV-A (55.7%) was more commonly observed than RSV-B (42.3%).
      59.8% and 90.1% of RSV-A infections were among children <=12 months and <=5 years
      old, respectively. On phylogenetic analysis of the second hypervariable region of
      the 112 RSV-A strains, 110 (98.2%) clustered within or adjacent to the NA1
      genotype; two isolates were GA5 genotype. Eleven (10%) NA1-related isolates
      clustered together phylogenetically as a novel RSV-A genotype, named ON1,
      containing a 72 nucleotide duplication in the C-terminal region of the attachment
      (G) glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and
      includes a23 amino acid duplication. Using RNA secondary structural software, a
      possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G
      gene duplication results in a repeat of 7 potential O-glycosylation sites
      including three O-linked sugar acceptors at residues 270, 275, and 283. Using
      Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively
      selected sites were observed among Ontario NA1 isolates; six were found to be
      codons which reverted to the previous state observed in the prototype RSV-A2
      strain. The tendency of codon regression in the G-ectodomain may infer a
      decreased avidity of antibody to the current circulating strains. Further work is
      needed to document and further understand the emergence, virulence, pathogenicity
      and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene
      duplication.

PMID- 22470428
TI  - Function of the active site lysine autoacetylation in Tip60 catalysis.
AB  - The 60-kDa HIV-Tat interactive protein (Tip60) is a key member of the MYST family
      of histone acetyltransferases (HATs) that plays critical roles in multiple
      cellular processes. We report here that Tip60 undergoes autoacetylation at
      several lysine residues, including a key lysine residue (i.e. Lys-327) in the
      active site of the MYST domain. The mutation of K327 to arginine led to loss of
      both the autoacetylation activity and the cognate HAT activity. Interestingly,
      deacetylated Tip60 still kept a substantial degree of HAT activity. We also
      investigated the effect of cysteine 369 and glutamate 403 in Tip60
      autoacetylation in order to understand the molecular pathway of the
      autoacetylation at K327. Together, we conclude that the acetylation of K327 which
      is located in the active site of Tip60 regulates but is not obligatory for the
      catalytic activity of Tip60. Since acetylation at this key residue appears to be
      evolutionarily conserved amongst all MYST proteins, our findings provide an
      interesting insight into the regulatory mechanism of MYST activities.

PMID- 22470429
TI  - Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in
      diabetic patients without cardiovascular events: the RATIONAL trial.
AB  - BACKGROUND: The systematic use of aspirin and statins in patients with diabetes
      and no previous cardiovascular events is controversial. We sought to assess the
      effects of aspirin and statins on the thrombotic risk assessed by thrombin
      generation (TG) among patients with type II diabetes mellitus and no previous
      cardiovascular events. METHODOLOGY/PRINCIPAL FINDINGS: Prospective, randomized,
      open, blinded to events evaluation, controlled, 2*2 factorial clinical trial
      including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40
      mg/d, both or none. Outcome measurements included changes in TG levels after
      treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At
      baseline all groups had similar clinical and biochemical profiles, including TG
      levels. There was no interaction between aspirin and atorvastatin. Atorvastatin
      significantly reduced TG measured as peak TG with saline (85.09+/-55.34 nmol vs
      153.26+/-75.55 nmol for atorvastatin and control groups, respectively; p =
      0.018). On the other hand, aspirin had no effect on TG (121.51+/-81.83 nmol vs
      116.85+/-67.66 nmol, for aspirin and control groups, respectively; p = 0.716).
      The effects of treatments on measurements of TG using other agonists were
      consistent. CONCLUSIONS/SIGNIFICANCE: While waiting for data from ongoing large
      clinical randomized trials to definitively outline the role of aspirin in primary
      prevention, our study shows that among diabetic patients without previous
      vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00793754.

PMID- 22470430
TI  - Enhanced auditory brainstem response and parental bonding style in children with
      gastrointestinal symptoms.
AB  - BACKGROUND: The electrophysiological properties of the brain and influence of
      parental bonding in childhood irritable bowel syndrome (IBS) are unclear. We
      hypothesized that children with chronic gastrointestinal (GI) symptoms like IBS
      may show exaggerated brainstem auditory evoked potential (BAEP) responses and
      receive more inadequate parental bonding. METHODOLOGY/PRINCIPAL FINDINGS:
      Children aged seven and their mothers (141 pairs) participated. BAEP was measured
      by summation of 1,000 waves of the electroencephalogram triggered by 75 dB click
      sounds. The mothers completed their Children's Somatization Inventory (CSI) and
      Parental Bonding Instrument (PBI). CSI results revealed 66 (42%) children without
      GI symptoms (controls) and 75 (58%) children with one or more GI symptoms (GI
      group). The III wave in the GI group (median 4.10 interquartile range [3.95-4.24]
      ms right, 4.04 [3.90-4.18] ms left) had a significantly shorter peak latency than
      controls (4.18 [4.06-4.34] ms right, p = 0.032, 4.13 [4.02-4.24] ms left, p =
      0.018). The female GI group showed a significantly shorter peak latency of the
      III wave (4.00 [3.90-4.18] ms) than controls (4.18 [3.97-4.31] ms, p = 0.034) in
      the right side. BAEP in the male GI group did not significantly differ from that
      in controls. GI scores showed a significant correlation with the peak latency of
      the III wave in the left side (rho = -0.192, p = 0.025). The maternal care PBI
      scores in the GI group (29 [26]-[33]) were significantly lower than controls (31
      [28.5-33], p = 0.010), while the maternal over-protection PBI scores were
      significantly higher in the GI group (16 [12]-[17]) than controls (13 [10.5-16],
      p = 0.024). Multiple regression analysis in females also supported these
      findings. CONCLUSIONS: It is suggested that children with chronic GI symptoms
      have exaggerated brainstem responses to environmental stimuli and inadequate
      parental behaviors aggravate these symptoms.

PMID- 22470431
TI  - Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing
      therapeutic potential of nutlin-3a by reversing multidrug resistance.
AB  - Retinoblastoma is the most common intraocular tumor in children. Malfunctioning
      of many signaling pathways regulating cell survival or apoptosis, make the
      disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1,
      lung-resistance protein (LRP) is the most challenging aspect to treat this
      disease. Presently, much attention has been given to the recently developed
      anticancer drug nutlin-3a because of its non-genotoxic nature and potency to
      activate tumor suppressor protein p53. However, being a substrate of multidrug
      resistance protein MRP1 and Pgp its application has become limited. Currently,
      research has step towards reversing Multi drug resistance (MDR) by using
      curcumin, however its clinical relevance is restricted by plasma instability and
      poor bioavailability. In the present investigation we tried to encapsulate nutlin
      3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to
      enhance therapeutic potential of nutlin-3a by modulating MDR. We document that
      curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a
      concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell
      cycle analysis and apoptosis studies were done to compare the effectiveness of
      native drugs (single or combined) and single or dual drug loaded nanoparticles
      (unconjugated/folate conjugated). The result demonstrated an augmented
      therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over
      other formulation. Enhanced expression or down regulation of
      proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and
      NFkappaB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is
      the first investigation exploring the role of curcumin as MDR modulator to
      enhance the therapeutic potentiality of nutlin-3a, which may opens new direction
      for targeting cancer with multidrug resistance phenotype.

PMID- 22470432
TI  - Using paleogenomics to study the evolution of gene families: origin and
      duplication history of the relaxin family hormones and their receptors.
AB  - Recent progress in the analysis of whole genome sequencing data has resulted in
      the emergence of paleogenomics, a field devoted to the reconstruction of
      ancestral genomes. Ancestral karyotype reconstructions have been used primarily
      to illustrate the dynamic nature of genome evolution. In this paper, we
      demonstrate how they can also be used to study individual gene families by
      examining the evolutionary history of relaxin hormones (RLN/INSL) and relaxin
      family peptide receptors (RXFP). Relaxin family hormones are members of the
      insulin superfamily, and are implicated in the regulation of a variety of
      primarily reproductive and neuroendocrine processes. Their receptors are G
      protein coupled receptors (GPCR's) and include members of two distinct
      evolutionary groups, an unusual characteristic. Although several studies have
      tried to elucidate the origins of the relaxin peptide family, the evolutionary
      origin of their receptors and the mechanisms driving the diversification of the
      RLN/INSL-RXFP signaling systems in non-placental vertebrates has remained
      elusive. Here we show that the numerous vertebrate RLN/INSL and RXFP genes are
      products of an ancestral receptor-ligand system that originally consisted of
      three genes, two of which apparently trace their origins to invertebrates.
      Subsequently, diversification of the system was driven primarily by whole genome
      duplications (WGD, 2R and 3R) followed by almost complete retention of the ligand
      duplicates in most vertebrates but massive loss of receptor genes in tetrapods.
      Interestingly, the majority of 3R duplicates retained in teleosts are potentially
      involved in neuroendocrine regulation. Furthermore, we infer that the ancestral
      AncRxfp3/4 receptor may have been syntenically linked to the AncRln-like ligand
      in the pre-2R genome, and show that syntenic linkages among ligands and receptors
      have changed dynamically in different lineages. This study ultimately shows the
      broad utility, with some caveats, of incorporating paleogenomics data into
      understanding the evolution of gene families.

PMID- 22470433
TI  - The colocalization potential of HIV-specific CD8+ and CD4+ T-cells is mediated by
      integrin beta7 but not CCR6 and regulated by retinoic acid.
AB  - CD4(+) T-cells from gut-associated lymphoid tissues (GALT) are major targets for
      HIV-1 infection. Recruitment of excess effector CD8(+) T-cells in the proximity
      of target cells is critical for the control of viral replication. Here, we
      investigated the colocalization potential of HIV-specific CD8(+) and CD4(+) T
      cells into the GALT and explored the role of retinoic acid (RA) in regulating
      this process in a cohort of HIV-infected subjects with slow disease progression.
      The expression of the gut-homing molecules integrin beta7, CCR6, and CXCR3 was
      identified as a "signature" for HIV-specific but not CMV-specific CD4(+) T-cells
      thus providing a new explanation for their enhanced permissiveness to infection
      in vivo. HIV-specific CD8(+) T-cells also expressed high levels of integrin beta7
      and CXCR3; however CCR6 was detected at superior levels on HIV-specific CD4(+)
      versus CD8(+) T-cells. All trans RA (ATRA) upregulated the expression of integrin
      beta7 but not CCR6 on HIV-specific T-cells. Together, these results suggest that
      HIV-specific CD8(+) T-cells may colocalize in excess with CD4(+) T-cells into the
      GALT via integrin beta7 and CXCR3, but not via CCR6. Considering our previous
      findings that CCR6(+)CD4(+) T-cells are major cellular targets for HIV-DNA
      integration in vivo, a limited ability of CD8(+) T-cells to migrate in the
      vicinity of CCR6(+)CD4(+) T-cells may facilitate HIV replication and
      dissemination at mucosal sites.

PMID- 22470434
TI  - Second language processing shows increased native-like neural responses after
      months of no exposure.
AB  - Although learning a second language (L2) as an adult is notoriously difficult,
      research has shown that adults can indeed attain native language-like brain
      processing and high proficiency levels. However, it is important to then retain
      what has been attained, even in the absence of continued exposure to the L2-
      particularly since periods of minimal or no L2 exposure are common. This event
      related potential (ERP) study of an artificial language tested performance and
      neural processing following a substantial period of no exposure. Adults learned
      to speak and comprehend the artificial language to high proficiency with either
      explicit, classroom-like, or implicit, immersion-like training, and then
      underwent several months of no exposure to the language. Surprisingly,
      proficiency did not decrease during this delay. Instead, it remained unchanged,
      and there was an increase in native-like neural processing of syntax, as
      evidenced by several ERP changes--including earlier, more reliable, and more left
      lateralized anterior negativities, and more robust P600s, in response to word
      order violations. Moreover, both the explicitly and implicitly trained groups
      showed increased native-like ERP patterns over the delay, indicating that such
      changes can hold independently of L2 training type. The results demonstrate that
      substantial periods with no L2 exposure are not necessarily detrimental. Rather,
      benefits may ensue from such periods of time even when there is no L2 exposure.
      Interestingly, both before and after the delay the implicitly trained group
      showed more native-like processing than the explicitly trained group, indicating
      that type of training also affects the attainment of native-like processing in
      the brain. Overall, the findings may be largely explained by a combination of
      forgetting and consolidation in declarative and procedural memory, on which L2
      grammar learning appears to depend. The study has a range of implications, and
      suggests a research program with potentially important consequences for second
      language acquisition and related fields.

PMID- 22470436
TI  - Factors associated with physician agreement and coding choices of cause of death
      using verbal autopsies for 1130 maternal deaths in India.
AB  - BACKGROUND: The Indian Sample Registration System (SRS) with verbal autopsy
      methods provides estimations of cause specific mortality for maternal deaths,
      where the majority of deaths occur at home, unregistered. We aim to examine
      factors that influence physician agreement and coding choices in assigning causes
      of death from verbal autopsies. METHODOLOGY/PRINCIPAL FINDINGS: Among adult
      deaths identified in the SRS, pregnancy-related deaths recorded in 2001-2003 were
      assigned ICD-10 codes by two independent physicians. Inter-rater reliability was
      estimated using Landis Koch Kappa classification <=0.4--poor to fair agreement;
      >0.4 <=0.6--moderate agreement; >0.6 <=0.8--substantial agreement; >8--high
      agreement. We identified factors associated with physician agreement using
      multivariate logistic regression. A central consensus panel reviewed cases for
      errors and reclassified as needed based on 2011 ICD-10 coding guidelines. Of 1130
      pregnancy-related deaths, 1040 were assigned ICD-10 codes by two physicians. We
      found substantial agreement regardless of the woman's residence, whether the
      death was registered, religion, respondent's or deceased's education, age,
      hospital admission or gestational age. Physician agreement was not influenced by
      the above variables, with the exception of greater agreement in cases where the
      respondent did not live with the deceased, or early gestational age at the time
      of death. A central consensus panel reviewed all cases and recoded 10% of cases
      due to insufficient use of information in the verbal autopsy by the coding
      physicians and rationale for this reclassification are discussed. CONCLUSION: In
      the absence of complete vital registration and universal healthcare services,
      physician coded verbal autopsies continues to be heavily relied upon to ascertain
      pregnancy-related death. From this study, two independent physicians had good
      inter-rater reliability for assigning pregnancy-related causes of death in a
      nationally-represented sample, and physician coding does not appear to be heavily
      influenced by case characteristics or demographics.

PMID- 22470435
TI  - Isolation and characterization of cytotoxic, aggregative Citrobacter freundii.
AB  - Citrobacter freundii is an infrequent but established cause of diarrhea in
      humans. However, little is known of its genetic diversity and potential for
      virulence. We analyzed 26 isolates, including 12 from human diarrheal patients, 2
      from human fecal samples of unknown diarrheal status, and 12 from animals,
      insects, and other sources. Pulsed field gel electrophoresis using XbaI allowed
      us to divide the 26 isolates into 20 pulse types, while multi-locus sequence
      typing using 7 housekeeping genes allowed us to divide the 26 isolates into 6
      sequence types (STs) with the majority belonging to 4 STs. We analyzed adhesion
      and cytotoxicity to HEp-2 cells in these 26 strains. All were found to adhere to
      HEp-2 cells. One strain, CF74, which had been isolated from a goat, showed the
      strongest aggregative adhesion pattern. Lactate dehydrogenase (LDH) released from
      HEp-2 cells was evaluated as a measure of cytotoxicity, averaging 7.46%. Strain
      CF74 induced the highest level of LDH, 24.3%, and caused >50% cell rounding,
      detachment, and death. We named strain CF74 "cytotoxic and aggregative C.
      freundii." Genome sequencing of CF74 revealed that it had acquired 7 genomic
      islands, including 2 fimbriae islands and a type VI secretion system island, all
      of which are potential virulence factors. Our results show that aggregative
      adherence and cytotoxicity play an important role in the pathogenesis of C.
      freundii.

PMID- 22470437
TI  - Mechanical force alters morphogenetic movements and segmental gene expression
      patterns during Drosophila embryogenesis.
AB  - The development of an organism is accompanied by various cellular morphogenetic
      movements, changes in cellular as well as nuclear morphology and transcription
      programs. Recent evidence suggests that intra and inter-cellular connections
      mediated by various adhesion proteins contribute to defining nuclear morphology.
      In addition, three dimensional organization of the cell nucleus regulate the
      transcription programs. However the link between cellular morphogenetic movements
      and its coupling to nuclear function in a developmental context is poorly
      understood. In this paper we use a point perturbation by tissue level laser
      ablation and sheet perturbation by application of force using magnetic tweezers
      to alter cellular morphogenetic movements and probe its impact on nuclear
      morphology and segmental gene expression patterns. Mechanical perturbations
      during blastoderm stage in a developing Drosophila embryo resulted in localized
      alterations in nuclear morphology and cellular movement. In addition, global
      defects in germ-band (GB) extension and retraction are observed when external
      force is applied during morphogenetic movements, suggesting a long-range physical
      coupling within the GB layer of cells. Further local application of force
      resulted in redistribution of non muscle myosin-II in the GB layer. Finally these
      perturbations lead to altered segmental gene (engrailed) expression patterns
      later during the development. Our observations suggest that there exists a tight
      regulation between nuclear morphology and cellular adhesive connections during
      morphogenetic movement of cells in the embryo. The observed spatial changes in
      patterning genes, with perturbation, highlight the importance of nuclear
      integrity to cellular movement in establishing gene expression program in a
      developmental system.

PMID- 22470438
TI  - Limited Awareness and Low Immediate Uptake of Pre-Exposure Prophylaxis among Men
      Who Have Sex with Men Using an Internet Social Networking Site.
AB  - BACKGROUND: In 2010, the iPrEx trial demonstrated that oral antiretroviral pre
      exposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk
      men who have sex with men (MSM). The impact of iPrEx on PrEP knowledge and actual
      use among at-risk MSM is unknown. Online surveys were conducted to assess PrEP
      awareness, interest and experience among at-risk MSM before and after iPrEx, and
      to determine demographic and behavioral factors associated with these measures.
      METHODS AND FINDINGS: Cross-sectional, national, internet-based surveys were
      administered to U.S. based members of the most popular American MSM social
      networking site 2 months before (n = 398) and 1 month after (n = 4 558)
      publication of iPrEx results. Comparisons were made between these samples with
      regards to PrEP knowledge, interest, and experience. Data were collected on
      demographics, sexual risk, and experience with post-exposure prophylaxis (PEP).
      Regression analyses were performed to identify factors associated with PrEP
      awareness, interest, and experience post-iPrEx. Most participants were white,
      educated, and indicated high-risk sexual behaviors. Awareness of PrEP was limited
      pre- and post-iPrEx (13% vs. 19%), whereas interest levels after being provided
      with a description of PrEP remained high (76% vs. 79%). PrEP use remained
      uncommon (0.7% vs. 0.9%). PrEP use was associated with PEP awareness (OR 7.46; CI
      1.52-36.6) and PEP experience (OR 34.2; CI 13.3-88.4). PrEP interest was
      associated with older age (OR 1.01; CI 1.00-1.02), unprotected anal intercourse
      with >=1 male partner in the prior 3 months (OR 1.40; CI 1.10-1.77), and
      perceiving oneself at increased risk for HIV acquisition (OR 1.20; CI 1.13-1.27).
      CONCLUSIONS: Among MSM engaged in online networking, awareness of PrEP was
      limited 1 month after the iPrEx data were released. Utilization was low, although
      some MSM who reported high-risk behaviors were interested in using PrEP. Studies
      are needed to understand barriers to PrEP utilization by at-risk MSM.

PMID- 22470439
TI  - The lone inventor: low success rates and common errors associated with pro-se
      patent applications.
AB  - A pro-se patent applicant is an inventor who chooses to represent himself while
      pursuing ("prosecuting") a patent application. To the author's knowledge, this
      paper is the first empirical study addressing how applications filed by pro-se
      inventors fare compared to applications in which inventors were represented by
      patent attorneys or agents. The prosecution history of 500 patent applications
      filed at the United States Patent and Trademark Office were analyzed: inventors
      were represented by a patent professional for 250 of the applications
      ("represented applications") but not in the other 250 ("pro-se applications").
      76% of the pro-se applications became abandoned (not issuing as a patent), as
      compared to 35% of the represented applications. Further, among applications that
      issued as patents, pro-se patents' claims appear to be narrower and therefore of
      less value than claims in the represented patent set. Case-specific data suggests
      that a substantial portion of pro-se applicants unintentionally abandon their
      applications, terminate the examination process relatively early, and/or fail to
      take advantage of interview opportunities that may resolve issues stalling
      allowance of the application.

PMID- 22470440
TI  - Induction of protective CD4+ T cell-mediated immunity by a Leishmania peptide
      delivered in recombinant influenza viruses.
AB  - The available evidence suggests that protective immunity to Leishmania is
      achieved by priming the CD4(+) Th1 response. Therefore, we utilised a reverse
      genetics strategy to generate influenza A viruses to deliver an immunogenic
      Leishmania peptide. The single, immunodominant Leishmania-specific LACK(158-173)
      CD4(+) peptide was engineered into the neuraminidase stalk of H1N1 and H3N2
      influenza A viruses. These recombinant viruses were used to vaccinate susceptible
      BALB/c mice to determine whether the resultant LACK(158-173)-specific CD4(+) T
      cell responses protected against live L. major infection. We show that
      vaccination with influenza-LACK(158-173) triggers LACK(158-173)-specific Th1
      biased CD4(+) T cell responses within an appropriate cytokine milieu (IFN-gamma,
      IL-12), essential for the magnitude and quality of the Th1 response. A single
      intraperitoneal exposure (non-replicative route of immunisation) to recombinant
      influenza delivers immunogenic peptides, leading to a marked reduction (2-4 log)
      in parasite burden, albeit without reduction in lesion size. This correlated with
      increased numbers of IFN-gamma-producing CD4(+) T cells in vaccinated mice
      compared to controls. Importantly, the subsequent prime-boost approach with a
      serologically distinct strain of influenza (H1N1->H3N2) expressing LACK(158-173)
      led to a marked reduction in both lesion size and parasite burdens in vaccination
      trials. This protection correlated with high levels of IFN-gamma producing cells
      in the spleen, which were maintained for 6 weeks post-challenge indicating the
      longevity of this protective effector response. Thus, these experiments show that
      Leishmania-derived peptides delivered in the context of recombinant influenza
      viruses are immunogenic in vivo, and warrant investigation of similar vaccine
      strategies to generate parasite-specific immunity.

PMID- 22470441
TI  - Human embryonic stem cells differentiated to lung lineage-specific cells
      ameliorate pulmonary fibrosis in a xenograft transplant mouse model.
AB  - BACKGROUND: Our aim was to differentiate human (h) embryonic stem (ES) cells into
      lung epithelial lineage-specific cells [i.e., alveolar epithelial type I (AEI)
      and type II (AEII) cells and Clara cells] as the first step in the development of
      cell-based strategies to repair lung injury in the bleomycin mouse model of
      idiopathic pulmonary fibrosis (IPF). A heterogeneous population of non-ciliated
      lung lineage-specific cells was derived by a novel method of embryoid body (EB)
      differentiation. This differentiated human cell population was used to modulate
      the profibrotic phenotype in transplanted animals. METHODOLOGY AND PRINCIPAL
      FINDINGS: Omission or inclusion of one or more components in the differentiation
      medium skewed differentiation of H7 hES cells into varying proportions of AEI,
      AEII, and Clara cells. ICG-001, a small molecule inhibitor of Wnt/beta
      catenin/Creb-binding protein (CBP) transcription, changed marker expression of
      the differentiated ES cells from an AEII-like phenotype to a predominantly AEI
      like phenotype. The differentiated cells were used in xenograft transplantation
      studies in bleomycin-treated Rag2gammaC(-/-) mice. Human cells were detected in
      lungs of the transplanted groups receiving differentiated ES cells treated with
      or without ICG-001. The increased lung collagen content found in bleomycin
      treated mice receiving saline was significantly reduced by transplantation with
      the lung-lineage specific epithelial cells differentiated from ES cells. A
      significant increase in progenitor number was observed in the airways of
      bleomycin-treated mice after transplantation of differentiated hES cells.
      CONCLUSIONS: This study indicates that ES cell-based therapy may be a powerful
      novel approach to ameliorate lung fibrosis.

PMID- 22470442
TI  - New insights into the skull of Istiodactylus latidens (Ornithocheiroidea,
      Pterodactyloidea).
AB  - The skull of the Cretaceous pterosaur Istiodactylus latidens, a historically
      important species best known for its broad muzzle of interlocking, lancet-shaped
      teeth, is almost completely known from the broken remains of several individuals,
      but the length of its jaws remains elusive. Estimates of I. latidens jaw length
      have been exclusively based on the incomplete skull of NHMUK R3877 and, perhaps
      erroneously, reconstructed by assuming continuation of its broken skull pieces as
      preserved in situ. Here, an overlooked jaw fragment of NHMUK R3877 is redescribed
      and used to revise the skull reconstruction of I. latidens. The new
      reconstruction suggests a much shorter skull than previously supposed, along with
      a relatively tall orbital region and proportionally slender maxilla, a feature
      documented in the early 20(th) century but ignored by all skull reconstructions
      of this species. These features indicate that the skull of I. latidens is
      particularly distinctive amongst istiodactylids and suggests greater disparity
      between I. latidens and I. sinensis than previously appreciated. A cladistic
      analysis of istiodactylid pterosaurs incorporating new predicted I. latidens
      skull metrics suggests Istiodactylidae is constrained to five species
      (Liaoxipterus brachyognathus, Lonchengpterus zhoai, Nurhachius ignaciobritoi,
      Istiodactylus latidens and Istiodactylus sinensis) defined by their distinctive
      dentition, but excludes the putative istiodactylids Haopterus gracilis and
      Hongshanopterus lacustris. Istiodactylus latidens, I. sinensis and Li.
      brachyognathus form an unresolved clade of derived istiodactylids, and the
      similarity of comparable remains of I. sinensis and Li. brachyognathus suggest
      further work into their taxonomy and classification is required. The new skull
      model of I. latidens agrees with the scavenging habits proposed for these
      pterosaurs, with much of their cranial anatomy converging on that of habitually
      scavenging birds.

PMID- 22470443
TI  - Microfluidic synthesis of microfibers for magnetic-responsive controlled drug
      release and cell culture.
AB  - This study demonstrated the fabrication of alginate microfibers using a modular
      microfluidic system for magnetic-responsive controlled drug release and cell
      culture. A novel two-dimensional fluid-focusing technique with multi-inlets and
      junctions was used to spatiotemporally control the continuous laminar flow of
      alginate solutions. The diameter of the manufactured microfibers, which ranged
      from 211 um to 364 um, could be well controlled by changing the flow rate of the
      continuous phase. While the model drug, diclofenac, was encapsulated into
      microfibers, the drug release profile exhibited the characteristic of a proper
      and steady release. Furthermore, the diclofenac release kinetics from the
      magnetic iron oxide-loaded microfibers could be controlled externally, allowing
      for a rapid drug release by applying a magnetic force. In addition, the
      successful culture of glioblastoma multiforme cells in the microfibers
      demonstrated a good structural integrity and environment to grow cells that could
      be applied in drug screening for targeting cancer cells. The proposed
      microfluidic system has the advantages of ease of fabrication, simplicity, and a
      fast and low-cost process that is capable of generating functional microfibers
      with the potential for biomedical applications, such as drug controlled release
      and cell culture.

PMID- 22470444
TI  - Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani
      population.
AB  - BACKGROUND: Hyperhomocysteinemia (>15 umol/L) is highly prevalent in South Asian
      populations including Pakistan. In order to investigate the genetic determinants
      of this condition, we studied 6 polymorphisms in genes of 3 enzymes-
      methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase
      (MS; A2756G), cystathionine-beta-synthase (CBS; T833C/844ins68, G919A) involved
      in homocysteine metabolism and investigated their interactions with nutritional
      and environmental factors in a Pakistani population. METHODOLOGY/PRINCIPAL
      FINDINGS: In a cross-sectional survey, 872 healthy adults (355 males and 517
      females; age 18-60 years) were recruited from a low-income urban population in
      Karachi. Fasting venous blood was obtained and assessed for plasma/serum
      homocysteine; folate, vitamin B12, pyridoxal phosphate and blood lead. DNA was
      isolated and genotyping was performed by PCR-RFLP (restriction-fragment-length
      polymorphism) based assays. The average changes in homocysteine levels for MTHFR
      677CT and TT genotypes were positive [beta(SE beta), 2.01(0.63) and 16.19(1.8)
      umol/L, respectively]. Contrary to MTHFR C677T polymorphism, the average changes
      in plasma homocysteine levels for MS 2756AG and GG variants were negative
      [beta(SE beta), -0.56(0.58) and -0.83(0.99) umol/L, respectively]. The average
      change occurring for CBS 844ins68 heterozygous genotype (ancestral/insertion) was
      -1.88(0.81) umol/L. The combined effect of MTHFR C677T, MS A2756G and CBS
      844ins68 genotypes for plasma homocysteine levels was additive (p value <0.001).
      Odds of having hyperhomocysteinemia with MTHFR 677TT genotype was 10-fold
      compared to MTHFR 677CC genotype [OR (95%CI); 10.17(3.6-28.67)]. Protective
      effect towards hyperhomocysteinemia was observed with heterozygous
      (ancestral/insertion) genotype of CBS 844ins68 compared to homozygous ancestral
      type [OR (95% CI); 0.58 (0.34-0.99)]. Individuals with MTHFR 677CT or TT
      genotypes were at a greater risk of hyperhomocysteinemia in folate and vitamin
      B12 deficiencies and high blood lead (p value <0.05) level. CONCLUSIONS: Gene
      polymorphism (especially MTHFR C677T transition), folate and vitamin B12
      deficiencies, male gender and high blood lead level appear to be contributing
      towards the development of hyperhomocysteinemia in a Pakistani population.

PMID- 22470445
TI  - In vivo determination of organellar pH using a universal wavelength-based
      confocal microscopy approach.
AB  - Many essential cellular processes are affected by transmembrane H(+) gradients
      and intracellular pH (pHi). The research of such metabolic events calls for a non
      invasive method to monitor pHi within individual subcellular compartments. We
      present a novel confocal microscopy approach for the determination of organellar
      pHi in living cells expressing pH-dependent ratiometric fluorescent proteins.
      Unlike conventional intensity-based fluorometry, our method relies on emission
      wavelength scans at single-organelle resolution to produce wavelength-based pH
      estimates both accurate and robust to low-signal artifacts. Analyses of Ato1p
      pHluorin and Ato1p-mCherry yeast cells revealed previously unreported wavelength
      shifts in pHluorin emission which, together with ratiometric mCherry, allowed for
      high-precision quantification of actual physiological pH values and evidenced
      dynamic pHi changes throughout the different stages of yeast colony development.
      Additionally, comparative pH quantification of Ato1p-pHluorin and Met17p-pHluorin
      cells implied the existence of a significant pHi gradient between peripheral and
      internal cytoplasm of cells from colonies occurring in the ammonia-producing
      alkali developmental phase. Results represent a step forward in the study of pHi
      regulation and subcellular metabolic functions beyond the scope of this study.

PMID- 22470446
TI  - Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.
AB  - The effect of microgravity on skeletal muscles has so far been examined in rat
      and mice only after short-term (5-20 day) spaceflights. The mice drawer system
      (MDS) program, sponsored by Italian Space Agency, for the first time aimed to
      investigate the consequences of long-term (91 days) exposure to microgravity in
      mice within the International Space Station. Muscle atrophy was present
      indistinctly in all fiber types of the slow-twitch soleus muscle, but was only
      slightly greater than that observed after 20 days of spaceflight. Myosin heavy
      chain analysis indicated a concomitant slow-to-fast transition of soleus. In
      addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase
      1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum
      longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up
      regulated, more in soleus than EDL, whereas Ca(2+)-activated K(+) channels were
      down-regulated, consistent with the phenotype transition. Gene expression of the
      atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and
      EDL muscles, whereas autophagy genes were in the control range. Muscle-specific
      IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL.
      Also, various stress-related genes were up-regulated in spaceflown EDL, not in
      soleus. Altogether, these results suggest that EDL muscle may resist to
      microgravity-induced atrophy by activating compensatory and protective pathways.
      Our study shows the extended sensitivity of antigravity soleus muscle after
      prolonged exposition to microgravity, suggests possible mechanisms accounting for
      the resistance of EDL, and individuates some molecular targets for the
      development of countermeasures.

PMID- 22470447
TI  - Characterization of rhodamine-123 as a tracer dye for use in in vitro drug
      transport assays.
AB  - Fluorescent tracer dyes represent an important class of sub-cellular probes and
      allow the examination of cellular processes in real-time with minimal impact upon
      these processes. Such tracer dyes are becoming increasingly used for the
      examination of membrane transport processes, as they are easy-to-use, cost
      effective probe substrates for a number of membrane protein transporters.
      Rhodamine 123, a member of the rhodamine family of flurone dyes, has been used to
      examine membrane transport by the ABCB1 gene product, MDR1. MDR1 is viewed as the
      archetypal drug transport protein, and is able to efflux a large number of
      clinically relevant drugs. In addition, ectopic activity of MDR1 has been
      associated with the development of multiple drug resistance phenotype, which
      results in a poor patient response to therapeutic intervention. It is thus
      important to be able to examine the potential for novel compounds to be MDR1
      substrates. Given the increasing use rhodamine 123 as a tracer dye for MDR1, a
      full characterisation of its spectral properties in a range of in vitro assay
      relevant media is warranted. Herein, we determine lambdamax for excitation and
      emission or rhodamine 123 and its metabolite rhodamine 110 in commonly used
      solvents and extraction buffers, demonstrating that fluorescence is highly
      dependent on the chemical environment: Optimal parameters are 1% (v/v) methanol
      in HBSS, with lambdaex = 505 nm, lambdaem = 525 nm. We characterise the uptake of
      rhodamine 123 into cells, via both passive and active processes, and demonstrate
      that this occurs primarily through OATP1A2-mediated facilitated transport at
      concentrations below 2 uM, and via micelle-mediated passive diffusion above this.
      Finally, we quantify the intracellular sequestration and metabolism of rhodamine
      123, demonstrating that these are both cell line-dependent factors that may
      influence the interpretation of transport assays.

PMID- 22470448
TI  - Antiretroviral outcomes in South African prisoners: a retrospective cohort
      analysis.
AB  - BACKGROUND AND METHODS: Little is known about antiretroviral therapy (ART)
      outcomes in prisoners in Africa. We conducted a retrospective review of outcomes
      of a large cohort of prisoners referred to a public sector, urban HIV clinic. The
      review included baseline characteristics, sequential CD4 cell counts and viral
      load results, complications and co-morbidities, mortality and loss to follow-up
      up to 96 weeks on ART. FINDINGS: 148 inmates (133 male) initiated on ART were
      included in the study. By week 96 on ART, 73% of all inmates enrolled in the
      study and 92% of those still accessing care had an undetectable viral load (<400
      copies/ml). The median CD4 cell count increased from 122 cells/mm(3) at baseline
      to 356 cells/mm(3) by 96 weeks. By study end, 96 (65%) inmates had ever received
      tuberculosis (TB) therapy with 63 (43%) receiving therapy during the study: 28%
      had a history of TB prior to ART initiation, 33% were on TB therapy at ART
      initiation and 22% developed TB whilst on ART. Nine (6%) inmates died, 7 in the
      second year on ART. Loss to follow-up (LTF) was common: 14 (9%) patients were LTF
      whilst still incarcerated, 11 (7%) were LTF post-release and 9 (6%) whose
      movements could not be traced. 16 (11%) inmates had inter-correctional facility
      transfers and 34 (23%) were released of whom only 23 (68%) returned to the ART
      clinic for ongoing follow-up. CONCLUSIONS: Inmates responded well to ART, despite
      a high frequency of TB/HIV co-infection. Attention should be directed towards
      ensuring eligible prisoners access ART programs promptly and that inter-facility
      transfers and release procedures facilitate continuity of care. Institutional TB
      control measures should remain a priority.

PMID- 22470449
TI  - Toxoplasma gondii infection in the brain inhibits neuronal degeneration and
      learning and memory impairments in a murine model of Alzheimer's disease.
AB  - Immunosuppression is a characteristic feature of Toxoplasma gondii-infected
      murine hosts. The present study aimed to determine the effect of the
      immunosuppression induced by T. gondii infection on the pathogenesis and
      progression of Alzheimer's disease (AD) in Tg2576 AD mice. Mice were infected
      with a cyst-forming strain (ME49) of T. gondii, and levels of inflammatory
      mediators (IFN-gamma and nitric oxide), anti-inflammatory cytokines (IL-10 and
      TGF-beta), neuronal damage, and beta-amyloid plaque deposition were examined in
      brain tissues and/or in BV-2 microglial cells. In addition, behavioral tests,
      including the water maze and Y-maze tests, were performed on T. gondii-infected
      and uninfected Tg2576 mice. Results revealed that whereas the level of IFN-gamma
      was unchanged, the levels of anti-inflammatory cytokines were significantly
      higher in T. gondii-infected mice than in uninfected mice, and in BV-2 cells
      treated with T. gondii lysate antigen. Furthermore, nitrite production from
      primary cultured brain microglial cells and BV-2 cells was reduced by the
      addition of T. gondii lysate antigen (TLA), and beta-amyloid plaque deposition in
      the cortex and hippocampus of Tg2576 mouse brains was remarkably lower in T.
      gondii-infected AD mice than in uninfected controls. In addition, water maze and
      Y-maze test results revealed retarded cognitive capacities in uninfected mice as
      compared with infected mice. These findings demonstrate the favorable effects of
      the immunosuppression induced by T. gondii infection on the pathogenesis and
      progression of AD in Tg2576 mice.

PMID- 22470450
TI  - Effects of hepatitis B virus S protein exposure on sperm membrane integrity and
      functions.
AB  - BACKGROUND: Hepatitis B is a public health problem worldwide. Viral infection can
      affect a man's fertility, but only scant information about the influence of
      hepatitis B virus (HBV) infection on sperm quality is available. The purpose of
      this study was to investigate the effect of hepatitis B virus S protein (HBs) on
      human sperm membrane integrity and functions. METHODS/PRINCIPAL FINDINGS:
      Reactive oxygen species (ROS), lipid peroxidation (LP), total antioxidant
      capacity (TAC) and phosphatidylserine (PS) externalization were determined. The
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      assays and flow cytometric analyses were performed. (1) After 3 h incubation with
      25 ug/ml of HBs, the average rates of ROS positive cells, annexin V
      positive/propidium iodide (PI)-negative cells, Caspases-3,-8,-9 positive cells
      and TUNEL-positive cells were significantly increased in the test groups as
      compared to those in the control groups, while TAC level was decreased when
      compared with the control. The level of malondialdehyde (MDA) in the sperm cells
      exposed to 50 ug/ml of HBs for 3 h was significantly higher than that in the
      control (P<0.05-0.01). (2) HBs increased the MDA levels and the numbers of ROS
      positive cells, annexin V-positive/PI-negative cells, caspases-3, -8, -9 positive
      cells and TUNEL-positive cells in a dose-dependent manner. (3) HBs monoclonal
      antibody (MAb) and N-Acetylcysteine (NAC) reduced the number of ROS-positive
      sperm cells. (4) HBs decreased the TAC levels in sperm cells in a dose-dependent
      manner. CONCLUSION: HBs exposure could lead to ROS generation, lipid
      peroxidation, TAC reduction, PS externalization, activation of caspases, and DNA
      fragmentation, resulting in increased apoptosis of sperm cells and loss of sperm
      membrane integrity and causing sperm dysfunctions.

PMID- 22470451
TI  - Chemoinformatic identification of novel inhibitors against Mycobacterium
      tuberculosis L-aspartate alpha-decarboxylase.
AB  - L-aspartate alpha-decarboxylase (ADC) belongs to a class of pyruvoyl dependent
      enzymes and catalyzes the conversion of aspartate to beta-alanine in the
      pantothenate pathway, which is critical for the growth of several micro
      organisms, including Mycobacterium tuberculosis (Mtb). Its presence only in micro
      organisms, fungi and plants and its absence in animals, particularly human, make
      it a promising drug target. We have followed a chemoinformatics-based approach to
      identify potential drug-like inhibitors against Mycobacterium tuberculosis L
      aspartate alpha-decarboxylase (MtbADC). The structure-based high throughput
      virtual screening (HTVS) mode of the Glide program was used to screen 333,761
      molecules of the Maybridge, National Cancer Institute (NCI) and Food and Drug
      Administration (FDA) approved drugs databases. Ligands were rejected if they
      cross-reacted with S-adenosylmethionine (SAM) decarboxylase, a human pyruvoyl
      dependent enzyme. The lead molecules were further analyzed for physicochemical
      and pharmacokinetic parameters, based on Lipinski's rule of five, and ADMET
      (absorption, distribution, metabolism, excretion and toxicity) properties. This
      analysis resulted in eight small potential drug-like inhibitors that are in
      agreement with the binding poses of the crystallographic ADC:fumarate and
      ADC:isoasparagine complex structures and whose backbone scaffolds seem to be
      suitable for further experimental studies in therapeutic development against
      tuberculosis.

PMID- 22470453
TI  - AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence
      of childhood narcolepsy in Finland.
AB  - BACKGROUND: Narcolepsy is a chronic sleep disorder with strong genetic
      predisposition causing excessive daytime sleepiness and cataplexy. A sudden
      increase in childhood narcolepsy was observed in Finland soon after pandemic
      influenza epidemic and vaccination with ASO3-adjuvanted Pandemrix. No increase
      was observed in other age groups. METHODS: Retrospective cohort study. From
      January 1, 2009 to December 31, 2010 we retrospectively followed the cohort of
      all children living in Finland and born from January 1991 through December 2005.
      Vaccination data of the whole population was obtained from primary health care
      databases. All new cases with assigned ICD-10 code of narcolepsy were identified
      and the medical records reviewed by two experts to classify the diagnosis of
      narcolepsy according to the Brighton collaboration criteria. Onset of narcolepsy
      was defined as the first documented contact to health care because of excessive
      daytime sleepiness. The primary follow-up period was restricted to August 15,
      2010, the day before media attention on post-vaccination narcolepsy started.
      FINDINGS: Vaccination coverage in the cohort was 75%. Of the 67 confirmed cases
      of narcolepsy, 46 vaccinated and 7 unvaccinated were included in the primary
      analysis. The incidence of narcolepsy was 9.0 in the vaccinated as compared to
      0.7/100,000 person years in the unvaccinated individuals, the rate ratio being
      12.7 (95% confidence interval 6.1-30.8). The vaccine-attributable risk of
      developing narcolepsy was 1:16,000 vaccinated 4 to 19-year-olds (95% confidence
      interval 1:13,000-1:21,000). CONCLUSIONS: Pandemrix vaccine contributed to the
      onset of narcolepsy among those 4 to 19 years old during the pandemic influenza
      in 2009-2010 in Finland. Further studies are needed to determine whether this
      observation exists in other populations and to elucidate potential underlying
      immunological mechanism. The role of the adjuvant in particular warrants further
      research before drawing conclusions about the use of adjuvanted pandemic vaccines
      in the future.

PMID- 22470452
TI  - Tamoxifen-Induced Cre-loxP Recombination Is Prolonged in Pancreatic Islets of
      Adult Mice.
AB  - Tamoxifen (Tm)-inducible Cre recombinases are widely used to perform gene
      inactivation and lineage tracing studies in mice. Although the efficiency of
      inducible Cre-loxP recombination can be easily evaluated with reporter strains,
      the precise length of time that Tm induces nuclear translocation of CreER(Tm) and
      subsequent recombination of a target allele is not well defined, and difficult to
      assess. To better understand the timeline of Tm activity in vivo, we developed a
      bioassay in which pancreatic islets with a Tm-inducible reporter (from Pdx1(PB)
      CreER(Tm);R26R(lacZ) mice) were transplanted beneath the renal capsule of adult
      mice previously treated with three doses of 1 mg Tm, 8 mg Tm, or corn oil
      vehicle. Surprisingly, recombination in islet grafts, as assessed by expression
      of the beta-galactosidase (beta-gal) reporter, was observed days or weeks after
      Tm treatment, in a dose-dependent manner. Substantial recombination occurred in
      islet grafts long after administration of 3*8 mg Tm: in grafts transplanted 48
      hours after the last Tm injection, 77.9+/-0.4% of beta-cells were beta-gal+; in
      beta-cells placed after 1 week, 46.2+/-5.0% were beta-gal+; after 2 weeks, 26.3+/
      7.0% were beta-gal+; and after 4 weeks, 1.9+/-0.9% were beta-gal+. Islet grafts
      from mice given 3*1 mg Tm showed lower, but notable, recombination 48 hours
      (4.9+/-1.7%) and 1 week (4.5+/-1.9%) after Tm administration. These results show
      that Tm doses commonly used to induce Cre-loxP recombination may continue to
      label significant numbers of cells for weeks after Tm treatment, possibly
      confounding the interpretation of time-sensitive studies using Tm-dependent
      models. Therefore, investigators developing experimental approaches using Tm
      inducible systems should consider both maximal recombination efficiency and the
      length of time that Tm-induced Cre-loxP recombination occurs.

PMID- 22470454
TI  - The ontogenetic osteohistology of Tenontosaurus tilletti.
AB  - Tenontosaurus tilletti is an ornithopod dinosaur known from the Early Cretaceous
      (Aptian-Albian) Cloverly and Antlers formations of the Western United States. It
      is represented by a large number of specimens spanning a number of ontogenetic
      stages, and these specimens have been collected across a wide geographic range
      (from central Montana to southern Oklahoma). Here I describe the long bone
      histology of T. tilletti and discuss histological variation at the individual,
      ontogenetic and geographic levels. The ontogenetic pattern of bone histology in
      T. tilletti is similar to that of other dinosaurs, reflecting extremely rapid
      growth early in life, and sustained rapid growth through sub-adult ontogeny. But
      unlike other iguanodontians, this dinosaur shows an extended multi-year period of
      slow growth as skeletal maturity approached. Evidence of termination of growth
      (e.g., an external fundamental system) is observed in only the largest
      individuals, although other histological signals in only slightly smaller
      specimens suggest a substantial slowing of growth later in life. Histological
      differences in the amount of remodeling and the number of lines of arrested
      growth varied among elements within individuals, but bone histology was
      conservative across sampled individuals of the species, despite known
      paleoenvironmental differences between the Antlers and Cloverly formations. The
      bone histology of T. tilletti indicates a much slower growth trajectory than
      observed for other iguanodontians (e.g., hadrosaurids), suggesting that those
      taxa reached much larger sizes than Tenontosaurus in a shorter time.

PMID- 22470455
TI  - Fusion of the Mycobacterium tuberculosis antigen 85A to an oligomerization domain
      enhances its immunogenicity in both mice and non-human primates.
AB  - To prevent important infectious diseases such as tuberculosis, malaria and HIV,
      vaccines inducing greater T cell responses are required. In this study, we
      investigated whether fusion of the M. tuberculosis antigen 85A to recently
      described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could
      increase T cell responses in pre-clinical vaccine model species. In mice, the
      fused antigen 85A showed consistent increases in CD4(+) and CD8(+) T cell
      responses after DNA and MVA vaccination. In rhesus macaques, higher IFN-gamma
      responses were observed in animals vaccinated with MVA-Ag85A IMX313 after both
      primary and secondary immunizations. In both animal models, fusion to IMX313
      induced a quantitative enhancement in the response without altering its quality:
      multifunctional cytokines were uniformly increased and differentiation into
      effector and memory T cell subsets was augmented rather than skewed. An extensive
      in vivo characterization suggests that IMX313 improves the initiation of immune
      responses as an increase in antigen 85A specific cells was observed as early as
      day 3 after vaccination. This report demonstrates that antigen multimerization
      using IMX313 is a simple and effective cross-species method to improve vaccine
      immunogenicity with potentially broad applicability.

PMID- 22470456
TI  - The origin and evolutionary history of HIV-1 subtype C in Senegal.
AB  - BACKGROUND: The classification of HIV-1 strains in subtypes and Circulating
      Recombinant Forms (CRFs) has helped in tracking the course of the HIV pandemic.
      In Senegal, which is located at the tip of West Africa, CRF02_AG predominates in
      the general population and Female Sex Workers (FSWs). In contrast, 40% of Men
      having Sex with Men (MSM) in Senegal are infected with subtype C. In this study
      we analyzed the geographical origins and introduction dates of HIV-1 C in Senegal
      in order to better understand the evolutionary history of this subtype, which
      predominates today in the MSM population METHODOLOGY/PRINCIPAL FINDINGS: We used
      a combination of phylogenetic analyses and a Bayesian coalescent-based approach,
      to study the phylogenetic relationships in pol of 56 subtype C isolates from
      Senegal with 3,025 subtype C strains that were sampled worldwide. Our analysis
      shows a significantly well supported cluster which contains all subtype C strains
      that circulate among MSM in Senegal. The MSM cluster and other strains from
      Senegal are widely dispersed among the different subclusters of African HIV-1 C
      strains, suggesting multiple introductions of subtype C in Senegal from many
      different southern and east African countries. More detailed analyses show that
      HIV-1 C strains from MSM are more closely related to those from southern Africa.
      The estimated date of the MRCA of subtype C in the MSM population in Senegal is
      estimated to be in the early 80's. CONCLUSIONS/SIGNIFICANCE: Our evolutionary
      reconstructions suggest that multiple subtype C viruses with a common ancestor
      originating in the early 1970s entered Senegal. There was only one efficient
      spread in the MSM population, which most likely resulted from a single
      introduction, underlining the importance of high-risk behavior in spread of
      viruses.

PMID- 22470457
TI  - Analysis of expressed sequence tags and characterization of a novel gene, Slmg7,
      in the midgut of the common cutworm, Spodoptera litura.
AB  - BACKGROUND: Out of total 3,081 assembled expressed sequence tags (ESTs) sequences
      representing 6,815 high-quality ESTs identified in three cDNA libraries
      constructed with RNA isolated from the midgut of Spodoptera litura, 1,039 ESTs
      showed significant hits and 1,107 ESTs did not show significant hits in BLAST
      searches. It is of interest to clarify whether or not these ESTs that did not
      show hits function in S. Litura. RESULTS: Twenty "no-hit" ESTs containing at
      least one putative open reading frame were selected for further expression
      analysis. The results from northern blot analysis showed that six of the selected
      ESTs are expressed in the larval midgut of this insect at different levels,
      suggesting that these ESTs represent true mRNA products, whereas the other 14
      ESTs could not be detected. Homologues of the four larval midgut-predominant
      genes (Slmg2, Slmg7, Slmg9 and Slmg17) were detected in the genomes of other
      lepidopteran insects but not in Drosophila melanogaster. A novel gene, Slmg7, is
      expressed at a high level specifically in the midgut during each of the larval
      stages. Slmg7 is a single copy gene and encodes a 143-amino acids protein. The
      SLMG7 protein was localized to the cytoplasm of Spli-221 cells. CONCLUSIONS: Six
      ESTs from the no hit list are transcribed into mRNA and are mainly expressed in
      the midgut of S. litura. Slmg7 is a novel gene that is localized to the
      cytoplasm.

PMID- 22470458
TI  - Early developing pig embryos mediate their own environment in the maternal tract.
AB  - The maternal tract plays a critical role in the success of early embryonic
      development providing an optimal environment for establishment and maintenance of
      pregnancy. Preparation of this environment requires an intimate dialogue between
      the embryo and her mother. However, many intriguing aspects remain unknown in
      this unique communication system. To advance our understanding of the process by
      which a blastocyst is accepted by the endometrium and better address the clinical
      challenges of infertility and pregnancy failure, it is imperative to decipher
      this complex molecular dialogue. The objective of the present work is to define
      the local response of the maternal tract towards the embryo during the earliest
      stages of pregnancy. We used a novel in vivo experimental model that eliminated
      genetic variability and individual differences, followed by Affymetrix microarray
      to identify the signals involved in this embryo-maternal dialogue. Using
      laparoscopic insemination one oviduct of a sow was inseminated with spermatozoa
      and the contralateral oviduct was injected with diluent. This model allowed us to
      obtain samples from the oviduct and the tip of the uterine horn containing either
      embryos or oocytes from the same sow. Microarray analysis showed that most of the
      transcripts differentially expressed were down-regulated in the uterine horn in
      response to blastocysts when compared to oocytes. Many of the transcripts altered
      in response to the embryo in the uterine horn were related to the immune system.
      We used an in silico mathematical model to demonstrate the role of the embryo as
      a modulator of the immune system. This model revealed that relatively modest
      changes induced by the presence of the embryo could modulate the maternal immune
      response. These findings suggested that the presence of the embryo might regulate
      the immune system in the maternal tract to allow the refractory uterus to
      tolerate the embryo and support its development.

PMID- 22470459
TI  - Rapamycin ameliorates kidney fibrosis by inhibiting the activation of mTOR
      signaling in interstitial macrophages and myofibroblasts.
AB  - Interstitial fibrosis is an inevitable outcome of all kinds of progressive
      chronic kidney disease (CKD). Emerging data indicate that rapamycin can
      ameliorate kidney fibrosis by reducing the interstitial infiltrates and
      accumulation of extra cellular matrix (ECM). However, the cellular mechanism that
      regulates those changes has not been well understood yet. In this study, we
      revealed the persistent activation of mammalian target of rapamycin (mTOR)
      signaling in the interstitial macrophages and myofibroblasts, but rarely in
      injured proximal epithelial cells, CD4+ T cells, neutrophils, or endothelial
      cells, during the development of kidney fibrosis. Administration of rapamycin to
      unilateral ureteral obstruction (UUO) mice significantly suppressed the
      immunoreactivity of mTOR signaling, which decreased the inflammatory responses
      and ECM accumulation in the obstructed kidneys. Isolated macrophages from
      rapamycin-treated obstructed kidneys presented less inflammatory activity than
      vehicle groups. In vitro study confirmed that rapamycin significantly inhibited
      the fibrogenic activation of cultured fibroblasts (NIH3T3 cells), which was
      induced by the stimulation of TGF-beta(1). Further experiment revealed that
      rapamycin did not directly inhibit the fibrogenesis of HK2 cells with
      aristolochic acid treatment. Our findings clarified that rapamycin can ameliorate
      kidney fibrosis by blocking the mTOR signaling in interstitial macrophages and
      myofibroblasts.

PMID- 22470460
TI  - Methylphenidate exposure induces dopamine neuron loss and activation of microglia
      in the basal ganglia of mice.
AB  - BACKGROUND: Methylphenidate (MPH) is a psychostimulant that exerts its
      pharmacological effects via preferential blockade of the dopamine transporter
      (DAT) and the norepinephrine transporter (NET), resulting in increased monoamine
      levels in the synapse. Clinically, methylphenidate is prescribed for the
      symptomatic treatment of ADHD and narcolepsy; although lately, there has been an
      increased incidence of its use in individuals not meeting the criteria for these
      disorders. MPH has also been misused as a "cognitive enhancer" and as an
      alternative to other psychostimulants. Here, we investigate whether chronic or
      acute administration of MPH in mice at either 1 mg/kg or 10 mg/kg, affects cell
      number and gene expression in the basal ganglia. METHODOLOGY/PRINCIPAL FINDINGS:
      Through the use of stereological counting methods, we observed a significant
      reduction (~20%) in dopamine neuron numbers in the substantia nigra pars compacta
      (SNpc) following chronic administration of 10 mg/kg MPH. This dosage of MPH also
      induced a significant increase in the number of activated microglia in the SNpc.
      Additionally, exposure to either 1 mg/kg or 10 mg/kg MPH increased the
      sensitivity of SNpc dopaminergic neurons to the parkinsonian agent 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP). Unbiased gene screening employing
      Affymetrix GeneChip(r) HT MG-430 PM revealed changes in 115 and 54 genes in the
      substantia nigra (SN) of mice exposed to 1 mg/kg and 10 mg/kg MPH doses,
      respectively. Decreases in the mRNA levels of gdnf, dat1, vmat2, and th in the
      substantia nigra (SN) were observed with both acute and chronic dosing of 10
      mg/kg MPH. We also found an increase in mRNA levels of the pro-inflammatory genes
      il-6 and tnf-alpha in the striatum, although these were seen only at an acute
      dose of 10 mg/kg and not following chronic dosing. CONCLUSION: Collectively, our
      results suggest that chronic MPH usage in mice at doses spanning the therapeutic
      range in humans, especially at prolonged higher doses, has long-term
      neurodegenerative consequences.

PMID- 22470461
TI  - Identification and characterization of paramyosin from cyst wall of metacercariae
      implicated protective efficacy against Clonorchis sinensis infection.
AB  - Human clonorchiasis has been increasingly prevalent in recent years and results
      in a threat to the public health in epidemic regions, motivating current
      strategies of vaccines to combat Clonorchis sinensis (C. sinensis). In this
      study, we identified C. sinensis paramyosin (CsPmy) from the cyst wall proteins
      of metacercariae by proteomic approaches and characterized the expressed
      recombinant pET-26b-CsPmy protein (101 kDa). Bioinformatics analysis indicated
      that full-length sequences of paramyosin are conserved in helminthes and numerous
      B-cell/T-cell epitopes were predicted in amino acid sequence of CsPmy. Western
      blot analysis showed that CsPmy was expressed at four life stages of C. sinensis,
      both cyst wall proteins and soluble tegumental components could be probed by anti
      CsPmy serum. Moreover, immunolocalization results revealed that CsPmy was
      specifically localized at cyst wall and excretory bladder of metacercaria, as
      well as the tegument, oral sucker and vitellarium of adult worm. Both immunoblot
      and immunolocalization results demonstrated that CsPmy was highly expressed at
      the stage of adult worm, metacercariae and cercaria, which could be supported by
      real-time PCR analysis. Both recombinant protein and nucleic acid of CsPmy showed
      strong immunogenicity in rats and induced combined Th1/Th2 immune responses,
      which were reflected by continuous high level of antibody titers and increased
      level of IgG1/IgG2a subtypes in serum. In vaccine trials, comparing with control
      groups, both CsPmy protein and DNA vaccine exhibited protective effect with
      significant worm reduction rate of 54.3% (p<0.05) and 36.1% (p<0.05),
      respectively. In consistence with immune responses in sera, elevated level of
      cytokines IFN-gamma and IL-4 in splenocytes suggested that CsPmy could induce
      combined cellular immunity and humoral immunity in host. Taken together, CsPmy
      could be a promising vaccine candidate in the prevention of C. sinensis regarding
      its high immunogenicity and surface localization.

PMID- 22470462
TI  - Molybdenum and phosphorus interact to constrain asymbiotic nitrogen fixation in
      tropical forests.
AB  - Biological di-nitrogen fixation (N(2)) is the dominant natural source of new
      nitrogen to land ecosystems. Phosphorus (P) is thought to limit N(2) fixation in
      many tropical soils, yet both molybdenum (Mo) and P are crucial for the
      nitrogenase reaction (which catalyzes N(2) conversion to ammonia) and cell
      growth. We have limited understanding of how and when fixation is constrained by
      these nutrients in nature. Here we show in tropical forests of lowland Panama
      that the limiting element on asymbiotic N(2) fixation shifts along a broad
      landscape gradient in soil P, where Mo limits fixation in P-rich soils while Mo
      and P co-limit in P-poor soils. In no circumstance did P alone limit fixation. We
      provide and experimentally test a mechanism that explains how Mo and P can
      interact to constrain asymbiotic N(2) fixation. Fixation is uniformly favored in
      surface organic soil horizons--a niche characterized by exceedingly low levels of
      available Mo relative to P. We show that soil organic matter acts to reduce
      molybdate over phosphate bioavailability, which, in turn, promotes Mo limitation
      in sites where P is sufficient. Our findings show that asymbiotic N(2) fixation
      is constrained by the relative availability and dynamics of Mo and P in soils.
      This conceptual framework can explain shifts in limitation status across broad
      landscape gradients in soil fertility and implies that fixation depends on Mo and
      P in ways that are more complex than previously thought.

PMID- 22470464
TI  - Time-integrated position error accounts for sensorimotor behavior in time
      constrained tasks.
AB  - Several studies have shown that human motor behavior can be successfully
      described using optimal control theory, which describes behavior by optimizing
      the trade-off between the subject's effort and performance. This approach
      predicts that subjects reach the goal exactly at the final time. However, another
      strategy might be that subjects try to reach the target position well before the
      final time to avoid the risk of missing the target. To test this, we have
      investigated whether minimizing the control effort and maximizing the performance
      is sufficient to describe human motor behavior in time-constrained motor tasks.
      In addition to the standard model, we postulate a new model which includes an
      additional cost criterion which penalizes deviations between the position of the
      effector and the target throughout the trial, forcing arrival on target before
      the final time. To investigate which model gives the best fit to the data and to
      see whether that model is generic, we tested both models in two different tasks
      where subjects used a joystick to steer a ball on a screen to hit a target (first
      task) or one of two targets (second task) before a final time. Noise of different
      amplitudes was superimposed on the ball position to investigate the ability of
      the models to predict motor behavior for different levels of uncertainty. The
      results show that a cost function representing only a trade-off between effort
      and accuracy at the end time is insufficient to describe the observed behavior.
      The new model correctly predicts that subjects steer the ball to the target
      position well before the final time is reached, which is in agreement with the
      observed behavior. This result is consistent for all noise amplitudes and for
      both tasks.

PMID- 22470463
TI  - Increased incidence and clinical picture of childhood narcolepsy following the
      2009 H1N1 pandemic vaccination campaign in Finland.
AB  - BACKGROUND: Narcolepsy is a rare neurological sleep disorder especially in
      children who are younger than 10 years. In the beginning of 2010, an
      exceptionally large number of Finnish children suffered from an abrupt onset of
      excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a
      systematic analysis of the incidence of narcolepsy in Finland between the years
      2002-2010. METHODS: All Finnish hospitals and sleep clinics were contacted to
      find out the incidence of narcolepsy in 2010. The national hospital discharge
      register from 2002 to 2009 was used as a reference. FINDINGS: Altogether 335
      cases (all ages) of narcolepsy were diagnosed in Finland during 2002-2009 giving
      an annual incidence of 0.79 per 100,000 inhabitants (95% confidence interval 0.62
      0.96). The average annual incidence among subjects under 17 years of age was 0.31
      (0.12-0.51) per 100,000 inhabitants. In 2010, 54 children under age 17 were
      diagnosed with narcolepsy (5.3/100,000; 17-fold increase). Among adults >=20
      years of age the incidence rate in 2010 was 0.87/100,000, which equals that in
      2002-2009. Thirty-four of the 54 children were HLA-typed, and they were all
      positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had
      received Pandemrix vaccination 0 to 242 days (median 42) before onset. All 50 had
      EDS with abnormal multiple sleep latency test (sleep latency <8 min and >=2 sleep
      onset REM periods). The symptoms started abruptly. Forty-seven (94%) had
      cataplexy, which started at the same time or soon after the onset of EDS.
      Psychiatric symptoms were common. Otherwise the clinical picture was similar to
      that described in childhood narcolepsy. INTERPRETATION: A sudden increase in the
      incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We
      consider it likely that Pandemrix vaccination contributed, perhaps together with
      other environmental factors, to this increase in genetically susceptible
      children.

PMID- 22470465
TI  - Exploiting adaptive laboratory evolution of Streptomyces clavuligerus for
      antibiotic discovery and overproduction.
AB  - Adaptation is normally viewed as the enemy of the antibiotic discovery and
      development process because adaptation among pathogens to antibiotic exposure
      leads to resistance. We present a method here that, in contrast, exploits the
      power of adaptation among antibiotic producers to accelerate the discovery of
      antibiotics. A competition-based adaptive laboratory evolution scheme is
      presented whereby an antibiotic-producing microorganism is competed against a
      target pathogen and serially passed over time until the producer evolves the
      ability to synthesize a chemical entity that inhibits growth of the pathogen.
      When multiple Streptomyces clavuligerus replicates were adaptively evolved
      against methicillin-resistant Staphylococcus aureus N315 in this manner, a strain
      emerged that acquired the ability to constitutively produce holomycin. In
      contrast, no holomycin could be detected from the unevolved wild-type strain.
      Moreover, genome re-sequencing revealed that the evolved strain had lost pSCL4, a
      large 1.8 Mbp plasmid, and acquired several single nucleotide polymorphisms in
      genes that have been shown to affect secondary metabolite biosynthesis. These
      results demonstrate that competition-based adaptive laboratory evolution can
      constitute a platform to create mutants that overproduce known antibiotics and
      possibly to discover new compounds as well.

PMID- 22470466
TI  - In silico investigation of potential SRC kinase ligands from traditional Chinese
      medicine.
AB  - Src kinase is an attractive target for drug development based on its established
      relationship with cancer and possible link to hypertension. The suitability of
      traditional Chinese medicine (TCM) compounds as potential drug ligands for
      further biological evaluation was investigated using structure-based, ligand
      based, and molecular dynamics (MD) analysis. Isopraeroside IV, 9alpha
      hydroxyfraxinellone-9-O-beta-D-glucoside (9HFG) and aurantiamide were the top
      three TCM candidates identified from docking. Hydrogen bonds and hydrophobic
      interactions were the primary forces governing docking stability. Their stability
      with Src kinase under a dynamic state was further validated through MD and
      torsion angle analysis. Complexes formed by TCM candidates have lower total
      energy estimates than the control Sacaratinib. Four quantitative-structural
      activity relationship (QSAR) in silico verifications consistently suggested that
      the TCM candidates have bioactive properties. Docking conformations of 9HFG and
      aurantiamide in the Src kinase ATP binding site suggest potential inhibitor-like
      characteristics, including competitive binding at the ATP binding site (Lys295)
      and stabilization of the catalytic cleft integrity. The TCM candidates have
      significantly lower ligand internal energies and are estimated to form more
      stable complexes with Src kinase than Saracatinib. Structure-based and ligand
      based analysis support the drug-like potential of 9HFG and aurantiamide and
      binding mechanisms reveal the tendency of these two candidates to compete for the
      ATP binding site.

PMID- 22470467
TI  - Characterisation of a peripheral neuropathic component of the rat monoiodoacetate
      model of osteoarthritis.
AB  - Joint degeneration observed in the rat monoiodoacetate (MIA) model of
      osteoarthritis shares many histological features with the clinical condition. The
      accompanying pain phenotype has seen the model widely used to investigate the
      pathophysiology of osteoarthritis pain, and for preclinical screening of
      analgesic compounds. We have investigated the pathophysiological sequellae of MIA
      used at low (1 mg) or high (2 mg) dose. Intra-articular 2 mg MIA induced
      expression of ATF-3, a sensitive marker for peripheral neuron stress/injury, in
      small and large diameter DRG cell profiles principally at levels L4 and 5 (levels
      predominated by neurones innervating the hindpaw) rather than L3. At the 7 day
      timepoint, ATF-3 signal was significantly smaller in 1 mg MIA treated animals
      than in the 2 mg treated group. 2 mg, but not 1 mg, intra-articular MIA was also
      associated with a significant reduction in intra-epidermal nerve fibre density in
      plantar hindpaw skin, and produced spinal cord dorsal and ventral horn
      microgliosis. The 2 mg treatment evoked mechanical pain-related hypersensitivity
      of the hindpaw that was significantly greater than the 1 mg treatment. MIA
      treatment produced weight bearing asymmetry and cold hypersensitivity which was
      similar at both doses. Additionally, while pregabalin significantly reduced deep
      dorsal horn evoked neuronal responses in animals treated with 2 mg MIA, this
      effect was much reduced or absent in the 1 mg or sham treated groups. These data
      demonstrate that intra-articular 2 mg MIA not only produces joint degeneration,
      but also evokes significant axonal injury to DRG cells including those
      innervating targets outside of the knee joint such as hindpaw skin. This
      significant neuropathic component needs to be taken into account when
      interpreting studies using this model, particularly at doses greater than 1 mg
      MIA.

PMID- 22470468
TI  - Activation of type I and III interferon signalling pathways occurs in lung
      epithelial cells infected with low pathogenic avian influenza viruses.
AB  - The host response to the low pathogenic avian influenza (LPAI) H5N2, H5N3 and
      H9N2 viruses were examined in A549, MDCK, and CEF cells using a systems-based
      approach. The H5N2 and H5N3 viruses replicated efficiently in A549 and MDCK
      cells, while the H9N2 virus replicated least efficiently in these cell types.
      However, all LPAI viruses exhibited similar and higher replication efficiencies
      in CEF cells. A comparison of the host responses of these viruses and the
      H1N1/WSN virus and low passage pH1N1 clinical isolates was performed in A549
      cells. The H9N2 and H5N2 virus subtypes exhibited a robust induction of Type I
      and Type III interferon (IFN) expression, sustained STAT1 activation from between
      3 and 6 hpi, which correlated with large increases in IFN-stimulated gene (ISG)
      expression by 10 hpi. In contrast, cells infected with the pH1N1 or H1N1/WSN
      virus showed only small increases in Type III IFN signalling, low levels of ISG
      expression, and down-regulated expression of the IFN type I receptor. JNK
      activation and increased expression of the pro-apoptotic XAF1 protein was
      observed in A549 cells infected with all viruses except the H1N1/WSN virus, while
      MAPK p38 activation was only observed in cells infected with the pH1N1 and the H5
      virus subtypes. No IFN expression and low ISG expression levels were generally
      observed in CEF cells infected with either AIV, while increased IFN and ISG
      expression was observed in response to the H1N1/WSN infection. These data suggest
      differences in the replication characteristics and antivirus signalling responses
      both among the different LPAI viruses, and between these viruses and the H1N1
      viruses examined. These virus-specific differences in host cell signalling
      highlight the importance of examining the host response to avian influenza
      viruses that have not been extensively adapted to mammalian tissue culture.

PMID- 22470469
TI  - Induction of apoptosis coupled to endoplasmic reticulum stress in human prostate
      cancer cells by n-butylidenephthalide.
AB  - BACKGROUND: N-butylidenephthalide (BP) exhibits antitumor effect in a variety of
      cancer cell lines. The objective of this study was to obtain additional insights
      into the mechanisms involved in BP induced cell death in human prostate cancer
      cells. METHODS/PRINCIPAL FINDINGS: Two human prostate cancer cell lines, PC-3 and
      LNCaP, were treated with BP, and subsequently evaluated for their viability and
      cell cycle profiles. BP caused cell cycle arrest and cell death in both cell
      lines. The G0/G1 phase arrest was correlated with increase levels of CDK
      inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. To
      determine the mechanisms of BP-induced growth arrest and cell death in prostate
      cancer cell lines, we performed a microarray study to identify alterations in
      gene expression induced by BP in the LNCaP cells. Several BP-induced genes,
      including the GADD153/CHOP, an endoplasmic reticulum stress (ER stress)-regulated
      gene, were identified. BP-induced ER stress was evidenced by increased expression
      of the downstream molecules GRP78/BiP, IRE1-alpha and GADD153/CHOP in both cell
      lines. Blockage of IRE1-alpha or GADD153/CHOP expression by siRNA significantly
      reduced BP-induced cell death in LNCaP cells. Furthermore, blockage of JNK1/2
      signaling by JNK siRNA resulted in decreased expression of IRE1-alpha and
      GADD153/CHOP genes, implicating that BP-induced ER stress may be elicited via
      JNK1/2 signaling in prostate cancer cells. BP also suppressed LNCaP xenograft
      tumor growth in NOD-SCID mice. It caused 68% reduction in tumor volume after 18
      days of treatment. CONCLUSIONS: Our results suggest that BP can cause G0/G1 phase
      arrest in prostate cancer cells and its cytotoxicity is mediated by ER stress
      induction. Thus, BP may serve as an anticancer agent by inducing ER stress in
      prostate cancer.

PMID- 22470470
TI  - Changes in prefrontal-limbic function in major depression after 15 months of long
      term psychotherapy.
AB  - Neuroimaging studies of depression have demonstrated treatment-specific changes
      involving the limbic system and regulatory regions in the prefrontal cortex.
      While these studies have examined the effect of short-term, interpersonal or
      cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic
      intervention has never been assessed. Here, we investigated recurrently depressed
      (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for
      sex, age, and education (N = 17) before and after 15 months of psychodynamic
      psychotherapy. Participants were scanned at two time points, during which
      presentations of attachment-related scenes with neutral descriptions alternated
      with descriptions containing personal core sentences previously extracted from an
      attachment interview. Outcome measure was the interaction of the signal
      difference between personal and neutral presentations with group and time, and
      its association with symptom improvement during therapy. Signal associated with
      processing personalized attachment material varied in patients from baseline to
      endpoint, but not in healthy controls. Patients showed a higher activation in the
      left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal
      cortex before treatment and a reduction in these areas after 15 months. This
      reduction was associated with improvement in depressiveness specifically, and in
      the medial prefrontal cortex with symptom improvement more generally. This is the
      first study documenting neurobiological changes in circuits implicated in
      emotional reactivity and control after long-term psychodynamic psychotherapy.

PMID- 22470471
TI  - Geolocators reveal migration and pre-breeding behaviour of the critically
      endangered Balearic Shearwater Puffinus mauretanicus.
AB  - Using combined miniature archival light and salt-water immersion loggers, we
      characterise the year-round individual at-sea movements of Europe's only
      critically endangered seabird, the Balearic shearwater Puffinus mauretanicus, for
      the first time. Focusing on the non-breeding period, we show that all of the 26
      breeding birds tracked from their breeding site on Mallorca in the Mediterranean
      Sea successfully made a 2-4 month migration into the Atlantic Ocean, where they
      utilised well-defined core areas off Portuguese and French coasts. As well as
      identifying high-risk areas in the Atlantic, our results confirm that breeding
      birds spend most of the year concentrated around productive waters of the Iberian
      shelf in the western Mediterranean. Migration phenology appeared largely
      unrelated to the subsequent (distinctly synchronous) breeding attempt, suggesting
      that any carry-over effects were compensated for during a long pre-laying period
      spent over winter in the Mediterranean. Using the light and salt-water immersion
      data alone we were also able to characterise the pattern of pre-laying visits to
      the colony in considerable detail, demonstrating that breeding pairs appear to
      coordinate their over-day visits using a high frequency of night-time visits
      throughout the winter. Our study shows that geolocation technology is a valuable
      tool for assessing the spatial distribution of risks to this critically
      endangered species, and also provides a low-impact method for remotely observing
      the detailed behaviour of seabird species that may be sensitive to disturbance
      from traditional study methods.

PMID- 22470472
TI  - Comparison of muscle transcriptome between pigs with divergent meat quality
      phenotypes identifies genes related to muscle metabolism and structure.
AB  - BACKGROUND: Meat quality depends on physiological processes taking place in
      muscle tissue, which could involve a large pattern of genes associated with both
      muscle structural and metabolic features. Understanding the biological phenomena
      underlying muscle phenotype at slaughter is necessary to uncover meat quality
      development. Therefore, a muscle transcriptome analysis was undertaken to compare
      gene expression profiles between two highly contrasted pig breeds, Large White
      (LW) and Basque (B), reared in two different housing systems themselves
      influencing meat quality. LW is the most predominant breed used in pig industry,
      which exhibits standard meat quality attributes. B is an indigenous breed with
      low lean meat and high fat contents, high meat quality characteristics, and is
      genetically distant from other European pig breeds. METHODOLOGY/PRINCIPAL
      FINDINGS: Transcriptome analysis undertaken using a custom 15 K microarray,
      highlighted 1233 genes differentially expressed between breeds (multiple-test
      adjusted P-value<0.05), out of which 635 were highly expressed in the B and 598
      highly expressed in the LW pigs. No difference in gene expression was found
      between housing systems. Besides, expression level of 12 differentially expressed
      genes quantified by real-time RT-PCR validated microarray data. Functional
      annotation clustering emphasized four main clusters associated to transcriptome
      breed differences: metabolic processes, skeletal muscle structure and
      organization, extracellular matrix, lysosome, and proteolysis, thereby
      highlighting many genes involved in muscle physiology and meat quality
      development. CONCLUSIONS/SIGNIFICANCE: Altogether, these results will contribute
      to a better understanding of muscle physiology and of the biological and
      molecular processes underlying meat quality. Besides, this study is a first step
      towards the identification of molecular markers of pork quality and the
      subsequent development of control tools.

PMID- 22470473
TI  - FRET imaging of diatoms expressing a biosilica-localized ribose sensor.
AB  - Future materials are envisioned to include bio-assembled, hybrid, three
      dimensional nanosystems that incorporate functional proteins. Diatoms are
      amenable to genetic modification for localization of recombinant proteins in the
      biosilica cell wall. However, the full range of protein functionalities that can
      be accommodated by the modified porous biosilica has yet to be described. Our
      objective was to functionalize diatom biosilica with a reagent-less sensor
      dependent on ligand-binding and conformational change to drive FRET-based
      signaling capabilities. A fusion protein designed to confer such properties
      included a bacterial periplasmic ribose binding protein (R) flanked by CyPet (C)
      and YPet (Y), cyan and yellow fluorescent proteins that act as a FRET pair. The
      structure and function of the CRY recombinant chimeric protein was confirmed by
      expression in E. coli prior to transformation of the diatom Thalassiosira
      pseudonana. Mass spectrometry of the recombinant CRY showed 97% identity with the
      deduced amino acid sequence. CRY with and without an N-terminal Sil3 tag for
      biosilica localization exhibited characteristic ribose-dependent changes in FRET,
      with similar dissociation constants of 123.3 uM and 142.8 uM, respectively. The
      addition of the Sil3 tag did not alter the affinity of CRY for the ribose
      substrate. Subsequent transformation of T. pseudonana with a vector encoding Sil3
      CRY resulted in fluorescence localization in the biosilica and changes in FRET in
      both living cells and isolated frustules in response to ribose. This work
      demonstrated that the nano-architecture of the genetically modified biosilica
      cell wall was able to support the functionality of the relatively complex Sil3
      CyPet-RBP-YPet fusion protein with its requirement for ligand-binding and
      conformational change for FRET-signal generation.

PMID- 22470474
TI  - Finite element analysis of osteosynthesis screw fixation in the bone stock: an
      appropriate method for automatic screw modelling.
AB  - The use of finite element analysis (FEA) has grown to a more and more important
      method in the field of biomedical engineering and biomechanics. Although
      increased computational performance allows new ways to generate more complex
      biomechanical models, in the area of orthopaedic surgery, solid modelling of
      screws and drill holes represent a limitation of their use for individual cases
      and an increase of computational costs. To cope with these requirements,
      different methods for numerical screw modelling have therefore been investigated
      to improve its application diversity. Exemplarily, fixation was performed for
      stabilization of a large segmental femoral bone defect by an osteosynthesis
      plate. Three different numerical modelling techniques for implant fixation were
      used in this study, i.e. without screw modelling, screws as solid elements as
      well as screws as structural elements. The latter one offers the possibility to
      implement automatically generated screws with variable geometry on arbitrary FE
      models. Structural screws were parametrically generated by a Python script for
      the automatic generation in the FE-software Abaqus/CAE on both a tetrahedral and
      a hexahedral meshed femur. Accuracy of the FE models was confirmed by
      experimental testing using a composite femur with a segmental defect and an
      identical osteosynthesis plate for primary stabilisation with titanium screws.
      Both deflection of the femoral head and the gap alteration were measured with an
      optical measuring system with an accuracy of approximately 3 um. For both screw
      modelling techniques a sufficient correlation of approximately 95% between
      numerical and experimental analysis was found. Furthermore, using structural
      elements for screw modelling the computational time could be reduced by 85% using
      hexahedral elements instead of tetrahedral elements for femur meshing. The
      automatically generated screw modelling offers a realistic simulation of the
      osteosynthesis fixation with screws in the adjacent bone stock and can be used
      for further investigations.

PMID- 22470475
TI  - E-cadherin destabilization accounts for the pathogenicity of missense mutations
      in hereditary diffuse gastric cancer.
AB  - E-cadherin is critical for the maintenance of tissue architecture due to its role
      in cell-cell adhesion. E-cadherin mutations are the genetic cause of Hereditary
      Diffuse Gastric Cancer (HDGC) and missense mutations represent a clinical burden,
      due to the uncertainty of their pathogenic role. In vitro and in vivo, most
      mutations lead to loss-of-function, although the causal factor is unknown for the
      majority. We hypothesized that destabilization could account for the
      pathogenicity of E-cadherin missense mutations in HDGC, and tested our hypothesis
      using in silico and in vitro tools. FoldX algorithm was used to calculate the
      impact of each mutation in E-cadherin native-state stability, and the analysis
      was complemented with evolutionary conservation, by SIFT. Interestingly, HDGC
      patients harbouring germline E-cadherin destabilizing mutants present a younger
      age at diagnosis or death, suggesting that the loss of native-state stability of
      E-cadherin accounts for the disease phenotype. To elucidate the biological
      relevance of E-cadherin destabilization in HDGC, we investigated a group of newly
      identified HDGC-associated mutations (E185V, S232C and L583R), of which L583R is
      predicted to be destabilizing. We show that this mutation is not functional in
      vitro, exhibits shorter half-life and is unable to mature, due to premature
      proteasome-dependent degradation, a phenotype reverted by stabilization with the
      artificial mutation L583I (structurally tolerated). Herein we report E-cadherin
      structural models suitable to predict the impact of the majority of cancer
      associated missense mutations and we show that E-cadherin destabilization leads
      to loss-of-function in vitro and increased pathogenicity in vivo.

PMID- 22470476
TI  - Asymmetrical dimethylarginine--more sensitive than NT-proBNP to diagnose heart
      failure in adults with congenital heart disease.
AB  - BACKGROUND: Chronic heart failure is an important cause for morbidity and
      mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an
      established biomarker for heart failure of non-congenital origin, its value in
      ACHD has limitations. Asymmetrical dimethylarginine (ADMA) correlates with
      disease severity and independently predicts adverse clinical events in heart
      failure of non-congenital origin. Its role in ACHD has not been investigated.
      METHODS: In 102 patients ADMA and NT-proBNP were measured and related to NYHA
      class, systemic ventricular function and parameters of cardiopulmonary exercise
      testing. RESULTS: In contrast to NT-proBNP ADMA differentiated between NYHA
      classes I-III. Both, ADMA and NT-proBNP showed a good correlation with parameters
      of cardiopulmonary exercise testing with comparable receiver-operating
      characteristic curves for identifying patients with severely limited
      cardiopulmonary exercise capacity. CONCLUSION: ADMA seems to be a better
      biomarker than NT-proBNP for the assessment of NYHA class and as a good as NT
      proBNP for the estimation of maximum exercise capacity in adults with congenital
      heart disease. Its use in clinical routine should be evaluated.

PMID- 22470477
TI  - Hierarchy measure for complex networks.
AB  - Nature, technology and society are full of complexity arising from the intricate
      web of the interactions among the units of the related systems (e.g., proteins,
      computers, people). Consequently, one of the most successful recent approaches to
      capturing the fundamental features of the structure and dynamics of complex
      systems has been the investigation of the networks associated with the above
      units (nodes) together with their relations (edges). Most complex systems have an
      inherently hierarchical organization and, correspondingly, the networks behind
      them also exhibit hierarchical features. Indeed, several papers have been devoted
      to describing this essential aspect of networks, however, without resulting in a
      widely accepted, converging concept concerning the quantitative characterization
      of the level of their hierarchy. Here we develop an approach and propose a
      quantity (measure) which is simple enough to be widely applicable, reveals a
      number of universal features of the organization of real-world networks and, as
      we demonstrate, is capable of capturing the essential features of the structure
      and the degree of hierarchy in a complex network. The measure we introduce is
      based on a generalization of the m-reach centrality, which we first extend to
      directed/partially directed graphs. Then, we define the global reaching
      centrality (GRC), which is the difference between the maximum and the average
      value of the generalized reach centralities over the network. We investigate the
      behavior of the GRC considering both a synthetic model with an adjustable level
      of hierarchy and real networks. Results for real networks show that our hierarchy
      measure is related to the controllability of the given system. We also propose a
      visualization procedure for large complex networks that can be used to obtain an
      overall qualitative picture about the nature of their hierarchical structure.

PMID- 22470478
TI  - Quercetin is more effective than cromolyn in blocking human mast cell cytokine
      release and inhibits contact dermatitis and photosensitivity in humans.
AB  - Mast cells are immune cells critical in the pathogenesis of allergic, but also
      inflammatory and autoimmune diseases through release of many pro-inflammatory
      cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin
      conditions that involve non-immune triggers such as substance P (SP), and do not
      respond to conventional treatment. Inhibition of mast cell cytokine release could
      be effective therapy for such diseases. Unfortunately, disodium cromoglycate
      (cromolyn), the only compound marketed as a mast cell "stabilizer", is not
      particularly effective in blocking human mast cells. Instead, flavonoids are
      potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory
      actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on
      cultured human mast cells. Que and cromolyn (100 uM) can effectively inhibit
      secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine,
      leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells
      (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn
      in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP.
      Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que
      inhibits cytosolic calcium level increase and NF-kappa B activation.
      Interestingly, Que is effective prophylactically, while cromolyn must be added
      together with the trigger or it rapidly loses its effect. In two pilot, open
      label, clinical trials, Que significantly decreased contact dermatitis and
      photosensitivity, skin conditions that do not respond to conventional treatment.
      In summary, Que is a promising candidate as an effective mast cell inhibitor for
      allergic and inflammatory diseases, especially in formulations that permit more
      sufficient oral absorption.

PMID- 22470479
TI  - Psychology of fragrance use: perception of individual odor and perfume blends
      reveals a mechanism for idiosyncratic effects on fragrance choice.
AB  - Cross-culturally, fragrances are used to modulate body odor, but the psychology
      of fragrance choice has been largely overlooked. The prevalent view is that
      fragrances mask an individual's body odor and improve its pleasantness. In two
      experiments, we found positive effects of perfume on body odor perception.
      Importantly, however, this was modulated by significant interactions with
      individual odor donors. Fragrances thus appear to interact with body odor,
      creating an individually-specific odor mixture. In a third experiment, the odor
      mixture of an individual's body odor and their preferred perfume was perceived as
      more pleasant than a blend of the same body odor with a randomly-allocated
      perfume, even when there was no difference in pleasantness between the perfumes.
      This indicates that fragrance use extends beyond simple masking effects and that
      people choose perfumes that interact well with their own odor. Our results
      provide an explanation for the highly individual nature of perfume choice.

PMID- 22470480
TI  - Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult
      male mice.
AB  - Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals
      (EDC) used as the base compound in the manufacture of polycarbonate plastics.
      Although evidence points to consider exposure to BPA as a risk factor for insulin
      resistance, its actions on whole body metabolism and on insulin-sensitive tissues
      are still unclear. The aim of the present work was to study the effects of low
      doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in
      adult mice. Adult mice were treated with subcutaneous injection of 100 ug/kg BPA
      or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo
      indirect calorimetry. Insulin signaling assays were conducted by western blot
      analysis. Mice treated with BPA were insulin resistant and had increased glucose
      stimulated insulin release. BPA-treated mice had decreased food intake, lower
      body temperature and locomotor activity compared to control. In skeletal muscle,
      insulin-stimulated tyrosine phosphorylation of the insulin receptor beta subunit
      was impaired in BPA-treated mice. This impairment was associated with a reduced
      insulin-stimulated Akt phosphorylation in the Thr(308) residue. Both skeletal
      muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen
      activated protein kinase (MAPK) signaling pathway was also impaired in the
      skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser
      intensity with decreased insulin-stimulated tyrosine phosphorylation of the
      insulin receptor beta subunit.In conclusion, short-term treatment with low doses
      of BPA slows down whole body energy metabolism and disrupts insulin signaling in
      peripheral tissues. Thus, our findings support the notion that BPA can be
      considered a risk factor for the development of type 2 diabetes.

PMID- 22470481
TI  - The influence of intense chemical pollution on the community composition,
      diversity and abundance of anammox bacteria in the Jiaojiang Estuary (China).
AB  - Continuous chemical pollution is one of the most serious environmental problems
      in the Jiaojiang Estuary of the East Sea (China). This chemical pollution has
      significantly changed the estuarine environmental conditions and may have
      profoundly influenced the distribution of anammox bacterial communities in this
      estuary. Here, we investigated the influence of chemical pollution on the
      community composition, diversity and abundance of anammox bacteria in Jiaojiang
      estuarine sediments. Phylogenetic analysis of 16S rRNA genes showed that the
      majority of anammox bacterial sequences retrieved from the estuarine intertidal
      sediments were associated with Kuenenia. In contrast, different anammox
      communities composed of Brocadia, Kuenenia, Scalindua and Jettenia were found in
      the estuarine subtidal sediments. Redundancy analysis (RDA) indicated that the
      sediment nitrobenzene and organic content had significant impacts on the
      distribution of anammox communities in the intertidal sediments. Pearson
      correlation analysis showed that the diversity of anammox bacteria in the
      intertidal sediments was positively correlated with the organic content. In
      contrast, RDA results showed that the nitrobenzene content, NO(3)(-)
      concentration and salinity significantly influenced the distribution of anammox
      communities in the subtidal sediments. The diversity and relative abundance of
      anammox bacteria in the subtidal sediments were positively correlated with NO(3)(
      ) concentration.

PMID- 22470482
TI  - De-novo assembly and analysis of the heterozygous triploid genome of the wine
      spoilage yeast Dekkera bruxellensis AWRI1499.
AB  - Despite its industrial importance, the yeast species Dekkera (Brettanomyces)
      bruxellensis has remained poorly understood at the genetic level. In this study
      we describe whole genome sequencing and analysis for a prevalent wine spoilage
      strain, AWRI1499. The 12.7 Mb assembly, consisting of 324 contigs in 99 scaffolds
      (super-contigs) at 26-fold coverage, exhibits a relatively high density of single
      nucleotide polymorphisms (SNPs). Haplotype sampling for 1.2% of open reading
      frames suggested that the D. bruxellensis AWRI1499 genome is comprised of a
      moderately heterozygous diploid genome, in combination with a divergent haploid
      genome. Gene content analysis revealed enrichment in membrane proteins,
      particularly transporters, along with oxidoreductase enzymes. Availability of
      this assembly and annotation provides a resource for further investigation of
      genomic organization in this species, and functional characterization of genes
      that may confer important phenotypic traits.

PMID- 22470483
TI  - The feasibility and impact of delivering a mind-body intervention in a virtual
      world.
AB  - INTRODUCTION: Mind-body medical approaches may ameliorate chronic disease. Stress
      reduction is particularly helpful, but face-to-face delivery systems cannot reach
      all those who might benefit. An online, 3-dimensional virtual world may be able
      to support the rich interpersonal interactions required of this approach. In this
      pilot study, we explore the feasibility of translating a face-to-face stress
      reduction program into an online virtual setting and estimate the effect size of
      the intervention. METHODS AND FINDINGS: Domain experts in virtual world
      technology joined with mind body practitioners to translate an existing 8 week
      relaxation response-based resiliency program into an 8-week virtual world-based
      program in Second LifeTM (SL). Twenty-four healthy volunteers with at least one
      month's experience in SL completed the program. Each subject filled out the
      Perceived Stress Scale (PSS) and the Symptom Checklist 90- Revised (SCL-90-R)
      before and after taking part. Participants took part in one of 3 groups of about
      10 subjects. The participants found the program to be helpful and enjoyable. Many
      reported that the virtual environment was an excellent substitute for the
      preferred face-to-face approach. On quantitative measures, there was a general
      trend toward decreased perceived stress, (15.7 to 15.0), symptoms of depression,
      (57.6 to 57.0) and anxiety (56.8 to 54.8). There was a significant decrease of
      2.8 points on the SCL-90-R Global Severity Index (p<0.05). CONCLUSIONS: This
      pilot project showed that it is feasible to deliver a typical mind-body medical
      intervention through a virtual environment and that it is well received.
      Moreover, the small reduction in psychological distress suggests further research
      is warranted. Based on the data collected for this project, a randomized trial
      with less than 50 subjects would be appropriately powered if perceived stress is
      the primary outcome.

PMID- 22470484
TI  - Tetrahydro iso-alpha acids from hops improve glucose homeostasis and reduce body
      weight gain and metabolic endotoxemia in high-fat diet-fed mice.
AB  - Obesity and related metabolic disorders such as insulin resistance and type 2
      diabetes are associated with a low-grade inflammatory state possibly through
      changes in gut microbiota composition and the development of higher plasma
      lipopolysaccharide (LPS) levels, i.e. metabolic endotoxemia. Various
      phytochemical compounds have been investigated as potential tools to regulate
      these metabolic features. Humulus lupulus L. (hops) contains several classes of
      compounds with anti-inflammatory potential. Recent evidence suggests that hops
      derived compounds positively impact adipocyte metabolism and glucose tolerance in
      obese and diabetic rodents via undefined mechanisms. In this study, we found that
      administration of tetrahydro iso-alpha acids (termed META060) to high-fat diet
      (HFD)-fed obese and diabetic mice for 8 weeks reduced body weight gain, the
      development of fat mass, glucose intolerance, and fasted hyperinsulinemia, and
      normalized insulin sensitivity markers. This was associated with reduced portal
      plasma LPS levels, gut permeability, and higher intestinal tight junction
      proteins Zonula occludens-1 and occludin. Moreover, META060 treatment increased
      the plasma level of the anti-inflammatory cytokine interleukin-10 and decreased
      the plasma level of the pro-inflammatory cytokine granulocyte colony-stimulating
      factor. In conclusion, this research allows us to decipher a novel mechanism
      contributing to the positive effects of META060 treatment, and supports the need
      to investigate such compounds in obese and type 2 diabetic patients.

PMID- 22470486
TI  - Structure-forming corals and sponges and their use as fish habitat in Bering Sea
      submarine canyons.
AB  - Continental margins are dynamic, heterogeneous settings that can include canyons,
      seamounts, and banks. Two of the largest canyons in the world, Zhemchug and
      Pribilof, cut into the edge of the continental shelf in the southeastern Bering
      Sea. Here currents and upwelling interact to produce a highly productive area,
      termed the Green Belt, that supports an abundance of fishes and squids as well as
      birds and marine mammals. We show that in some areas the floor of these canyons
      harbors high densities of gorgonian and pennatulacean corals and sponges, likely
      due to enhanced surface productivity, benthic currents and seafloor topography.
      Rockfishes, including the commercially important Pacific ocean perch, Sebastes
      alutus, were associated with corals and sponges as well as with isolated
      boulders. Sculpins, poachers and pleuronectid flounders were also associated with
      corals in Pribilof Canyon, where corals were most abundant. Fishes likely use
      corals and sponges as sources of vertical relief, which may harbor prey as well
      as provide shelter from predators. Boulders may be equivalent habitat in this
      regard, but are sparse in the canyons, strongly suggesting that biogenic
      structure is important fish habitat. Evidence of disturbance to the benthos from
      fishing activities was observed in these remote canyons. Bottom trawling and
      other benthic fishing gear has been shown to damage corals and sponges that may
      be very slow to recover from such disturbance. Regulation of these destructive
      practices is key to conservation of benthic habitats in these canyons and the
      ecosystem services they provide.

PMID- 22470485
TI  - Ocular application of the kinin B1 receptor antagonist LF22-0542 inhibits retinal
      inflammation and oxidative stress in streptozotocin-diabetic rats.
AB  - PURPOSE: Kinin B(1) receptor (B(1)R) is upregulated in retina of Streptozotocin
      (STZ)-diabetic rats and contributes to vasodilation of retinal microvessels and
      breakdown of the blood-retinal barrier. Systemic treatment with B(1)R antagonists
      reversed the increased retinal plasma extravasation in STZ rats. The present
      study aims at determining whether ocular application of a water soluble B(1)R
      antagonist could reverse diabetes-induced retinal inflammation and oxidative
      stress. METHODS: Wistar rats were made diabetic with STZ (65 mg/kg, i.p.) and 7
      days later, they received one eye drop application of LF22-0542 (1% in saline)
      twice a day for a 7 day-period. The impact was determined on retinal vascular
      permeability (Evans blue exudation), leukostasis (leukocyte infiltration using
      Fluorescein-isothiocyanate (FITC)-coupled Concanavalin A lectin), retinal mRNA
      levels (by qRT-PCR) of inflammatory (B(1)R, iNOS, COX-2, ICAM-1, VEGF-A, VEGF
      receptor type 2, IL-1beta and HIF-1alpha) and anti-inflammatory (B(2)R, eNOS)
      markers and retinal level of superoxide anion (dihydroethidium staining).
      RESULTS: Retinal plasma extravasation, leukostasis and mRNA levels of B(1)R,
      iNOS, COX-2, VEGF receptor type 2, IL-1beta and HIF-1alpha were significantly
      increased in diabetic retinae compared to control rats. All these abnormalities
      were reversed to control values in diabetic rats treated with LF22-0542. B(1)R
      antagonist also significantly inhibited the increased production of superoxide
      anion in diabetic retinae. CONCLUSION: B(1)R displays a pathological role in the
      early stage of diabetes by increasing oxidative stress and pro-inflammatory
      mediators involved in retinal vascular alterations. Hence, topical application of
      kinin B(1)R antagonist appears a highly promising novel approach for the
      treatment of diabetic retinopathy.

PMID- 22470487
TI  - The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide gene
      expression.
AB  - Hosts have developed diverse mechanisms to counter the pathogens they face in
      their natural environment. Throughout the plant and animal kingdoms, the up
      regulation of antimicrobial peptides is a common response to infection. In C.
      elegans, infection with the natural pathogen Drechmeria coniospora leads to rapid
      induction of antimicrobial peptide gene expression in the epidermis. Through a
      large genetic screen we have isolated many new mutants that are incapable of
      upregulating the antimicrobial peptide nlp-29 in response to infection (i.e. with
      a Nipi or 'no induction of peptide after infection' phenotype). More than half of
      the newly isolated Nipi mutants do not correspond to genes previously associated
      with the regulation of antimicrobial peptides. One of these, nipi-4, encodes a
      member of a nematode-specific kinase family. NIPI-4 is predicted to be
      catalytically inactive, thus to be a pseudokinase. It acts in the epidermis
      downstream of the PKC? TPA-1, as a positive regulator of nlp antimicrobial
      peptide gene expression after infection. It also controls the constitutive
      expression of antimicrobial peptide genes of the cnc family that are targets of
      TGFbeta regulation. Our results open the way for a more detailed understanding of
      how host defense pathways can be molded by environmental pathogens.

PMID- 22470489
TI  - An ancient relation between units of length and volume based on a sphere.
AB  - The modern metric system defines units of volume based on the cube. We propose
      that the ancient Egyptian system of measuring capacity employed a similar
      concept, but used the sphere instead. When considered in ancient Egyptian units,
      the volume of a sphere, whose circumference is one royal cubit, equals half a
      hekat. Using the measurements of large sets of ancient containers as a database,
      the article demonstrates that this formula was characteristic of Egyptian and
      Egyptian-related pottery vessels but not of the ceramics of Mesopotamia, which
      had a different system of measuring length and volume units.

PMID- 22470488
TI  - Identification of a novel signaling pathway and its relevance for GluA1
      recycling.
AB  - We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3)
      increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane.
      The activation of AMPA receptors by NMDA-type glutamate receptors eventually
      leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is
      upregulated in the hippocampus of new-born wild type Wistar rats after NMDA
      receptor activation. We further demonstrate in the Xenopus oocyte expression
      system that delivery of GluA1 protein to the plasma membrane depends on the small
      GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and
      activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve) and the generation
      of PI(3,5)P(2). In line with this mechanism we could show PIKfyve mRNA expression
      in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by
      SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636
      revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary
      hippocampal neurons with YM201636 altered the GluA1 expression pattern towards
      reduced synaptic expression of GluA1. Our findings demonstrate for the first time
      an involvement of PIKfyve and PI(3,5)P(2) in NMDA receptor-triggered synaptic
      GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to
      synaptic plasticity and memory.

PMID- 22470490
TI  - Intrauterine growth restriction is a direct consequence of localized maternal
      uropathogenic Escherichia coli cystitis.
AB  - Despite the continually increasing rates of adverse perinatal outcomes across the
      globe, the molecular mechanisms that underlie adverse perinatal outcomes are not
      completely understood. Clinical studies report that 10% of pregnant women will
      experience a urinary tract infection (UTI) and there is an association of UTIs
      with adverse perinatal outcomes. We introduced bacterial cystitis into
      successfully outbred female mice at gestational day 14 to follow pregnancy
      outcomes and immunological responses to determine the mechanisms that underlie
      UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing
      localized cystitis displayed intrauterine growth restriction (20-80%) as early as
      48 hours post-infection and throughout the remainder of normal gestation. Robust
      infiltration of cellular innate immune effectors was observed in the
      uteroplacental tissue following introduction of UTI despite absence of viable
      bacteria. The magnitude of serum proinflammatory cytokines is elevated in the
      maternal serum during UTI. This study demonstrates that a localized infection can
      dramatically impact the immunological status as well as the function of non
      infected distal organs and tissues. This model can be used as a platform to
      determine the mechanism(s) by which proinflammatory changes occur between non
      contiguous genitourinary organs.

PMID- 22470491
TI  - Comparison of statistical population reconstruction using full and pooled adult
      age-class data.
AB  - BACKGROUND: Age-at-harvest data are among the most commonly collected, yet
      neglected, demographic data gathered by wildlife agencies. Statistical population
      construction techniques can use this information to estimate the abundance of
      wild populations over wide geographic areas and concurrently estimate
      recruitment, harvest, and natural survival rates. Although current reconstruction
      techniques use full age-class data (0.5, 1.5, 2.5, 3.5, ... years), it is not
      always possible to determine an animal's age due to inaccuracy of the methods,
      expense, and logistics of sample collection. The ability to inventory wild
      populations would be greatly expanded if pooled adult age-class data (e.g., 0.5,
      1.5, 2.5+ years) could be successfully used in statistical population
      reconstruction. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the performance
      of statistical population reconstruction models developed to analyze full age
      class and pooled adult age-class data. We performed Monte Carlo simulations using
      a stochastic version of a Leslie matrix model, which generated data over a wide
      range of abundance levels, harvest rates, and natural survival probabilities,
      representing medium-to-big game species. Results of full age-class and pooled
      adult age-class population reconstructions were compared for accuracy and
      precision. No discernible difference in accuracy was detected, but precision was
      slightly reduced when using the pooled adult age-class reconstruction. On
      average, the coefficient of variation (i.e., SE(theta)/theta) increased by 0.059
      when the adult age-class data were pooled prior to analyses. The analyses and
      maximum likelihood model for pooled adult age-class reconstruction are
      illustrated for a black-tailed deer (Odocoileus hemionus) population in
      Washington State. CONCLUSIONS/SIGNIFICANCE: Inventorying wild populations is one
      of the greatest challenges of wildlife agencies. These new statistical population
      reconstruction models should expand the demographic capabilities of wildlife
      agencies that have already collected pooled adult age-class data or are seeking a
      cost-effective method for monitoring the status and trends of our wild resources.

PMID- 22470492
TI  - Degradation of internalized alphavbeta5 integrin is controlled by uPAR bound uPA:
      effect on beta1 integrin activity and alpha-SMA stress fiber assembly.
AB  - Myofibroblasts (Mfs) that persist in a healing wound promote extracellular matrix
      (ECM) accumulation and excessive tissue contraction. Increased levels of integrin
      alphavbeta5 promote the Mf phenotype and other fibrotic markers. Previously we
      reported that maintaining uPA (urokinase plasminogen activator) bound to its cell
      surface receptor, uPAR prevented TGFbeta-induced Mf differentiation. We now
      demonstrate that uPA/uPAR controls integrin beta5 protein levels and in turn, the
      Mf phenotype. When cell-surface uPA was increased, integrin beta5 levels were
      reduced (61%). In contrast, when uPA/uPAR was silenced, integrin beta5 total and
      cell-surface levels were increased (2-4 fold). Integrin beta5 accumulation
      resulted from a significant decrease in beta5 ubiquitination leading to a
      decrease in the degradation rate of internalized beta5. uPA-silencing also
      induced alpha-SMA stress fiber organization in cells that were seeded on
      collagen, increased cell area (1.7 fold), and increased integrin beta1 binding to
      the collagen matrix, with reduced activation of beta1. Elevated cell-surface
      integrin beta5 was necessary for these changes after uPA-silencing since blocking
      alphavbeta5 function reversed these effects. Our data support a novel mechanism
      by which downregulation of uPA/uPAR results in increased integrin alphavbeta5
      cell-surface protein levels that regulate the activity of beta1 integrins,
      promoting characteristics of the persistent Mf.

PMID- 22470493
TI  - Stathmin1 plays oncogenic role and is a target of microRNA-223 in gastric cancer.
AB  - Stathmin1 (STMN1) is a candidate oncoprotein and prognosis marker in several
      kinds of cancers. This study was aimed to analyze its expression and biological
      functions in gastric cancer. The expression of STMN1 was evaluated by qRT-PCR,
      western blot and immunohistochemistry. The biological function of STMN1 was
      determined by MTT proliferation assays, monolayer colony formation and cell
      invasion assays using small interference RNA technique in gastric cancer cell
      lines. We also explored the regulation of STMN1 expression by microRNA-223. STMN1
      was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas.
      STMN1-positive tumors were more likely to be found in old age group and
      associated with p53 nuclear expression. In diffuse type gastric adenocarcinomas,
      STMN1 expression was correlated with age (p = 0.043), T stage (p = 0.004) and
      lymph node metastasis (p = 0.046). Expression of STMN1 in diffuse type gastric
      adenocarcinoma was associated with poor disease specific survival by univariate
      analysis (p = 0.01). STMN1 knockdown in AGS and MKN7 cell lines suppressed
      proliferation (p<0.001), reduced monolayer colony formation (p<0.001), inhibited
      cell invasion and migration ability (p<0.001) and induced G1 phase arrest.
      siSTMN1 could also suppress cell growth in vivo (p<0. 01). We finally confirmed
      that STMN1 is a putative downstream target of miR-223 in gastric cancer. Our
      findings supported an oncogenic role of STMN1 in gastric cancer. STMN1 might
      serve as a prognostic marker and a potential therapeutic target for gastric
      cancer.

PMID- 22470495
TI  - Source analysis of beta-synchronisation and cortico-muscular coherence after
      movement termination based on high resolution electroencephalography.
AB  - We hypothesized that post-movement beta synchronization (PMBS) and cortico
      muscular coherence (CMC) during movement termination relate to each other and
      have similar role in sensorimotor integration. We calculated the parameters and
      estimated the sources of these phenomena.We measured 64-channel EEG
      simultaneously with surface EMG of the right first dorsal interosseus muscle in
      11 healthy volunteers. In Task1, subjects kept a medium-strength contraction
      continuously; in Task2, superimposed on this movement, they performed repetitive
      self-paced short contractions. In Task3 short contractions were executed alone.
      Time-frequency analysis of the EEG and CMC was performed with respect to the
      offset of brisk movements and averaged in each subject. Sources of PMBS and CMC
      were also calculated.High beta power in Task1, PMBS in Task2-3, and CMC in Task1
      2 could be observed in the same individual frequency bands. While beta
      synchronization in Task1 and PMBS in Task2-3 appeared bilateral with
      contralateral predominance, CMC in Task1-2 was strictly a unilateral phenomenon;
      their main sources did not differ contralateral to the movement in the primary
      sensorimotor cortex in 7 of 11 subjects in Task1, and in 6 of 9 subjects in
      Task2. In Task2, CMC and PMBS had the same latency but their amplitudes did not
      correlate with each other. In Task2, weaker PMBS source was found bilaterally
      within the secondary sensory cortex, while the second source of CMC was detected
      in the premotor cortex, contralateral to the movement. In Task3, weaker sources
      of PMBS could be estimated in bilateral supplementary motor cortex and in the
      thalamus. PMBS and CMC appear simultaneously at the end of a phasic movement
      possibly suggesting similar antikinetic effects, but they may be separate
      processes with different active functions. Whereas PMBS seems to reset the
      supraspinal sensorimotor network, cortico-muscular coherence may represent the
      recalibration of cortico-motoneuronal and spinal systems.

PMID- 22470494
TI  - Chronic immune activation in HIV-1 infection contributes to reduced interferon
      alpha production via enhanced CD40:CD40 ligand interaction.
AB  - Although a signature of increased interferon (IFN-)alpha production is observed
      in HIV-1 infection, the response of circulating plasmacytoid dendritic cells
      (PDC) to Toll-like receptor ligand stimulation is substantially impaired. This
      functional PDC deficit, which we specifically observed in HIV-1 infected
      individuals with less than 500 CD4+ T cells/ul, is not well understood. We
      provide evidence that the peripheral IFN-alpha production in HIV-1 infection is
      actively suppressed by the enhanced interaction of CD40 ligand (CD40L), a member
      of the tumor necrosis factor family, and its receptor CD40, which are both
      upregulated upon immune activation. Plasma levels of soluble CD40L were
      significantly higher in untreated HIV-1 infected individuals (n = 52) than in
      subjects on long-term antiretroviral therapy (n = 62, p<0.03) and in uninfected
      control donors (n = 16, p<0.001). Concomitantly, cell-associated CD40L and the
      expression of the receptor CD40 on the PDC were significantly upregulated in HIV
      1 infection (p<0.05). Soluble and cell-associated CD40L inhibited the PDC-derived
      IFN-alpha production by CpG oligodeoxynucleotides dose-dependently. This
      suppressive effect was observed at much lower, physiological CD40L concentrations
      in peripheral blood mononuclear cells (PBMC) of HIV-1 infected individuals
      compared to controls (p<0.05). The CpG-induced IFN-alpha production in PBMC of
      HIV-1 infected donors was directly correlated with PDC and CD4+ T cell counts,
      and inversely correlated with the viral loads (p<0.001). In HIV-1 infected donors
      with less than 500 CD4+ T cells/ul, the CpG-induced IFN-alpha production was
      significantly correlated with the percentage of CD40-expressing PDC and the level
      of CD40 expression on these cells (p<0.05), whereas CD40L plasma levels played a
      minor role. In addition, low-dose CD40L contributed to the enhanced production of
      interleukin 6 and 8 in PBMC of HIV-1 infected donors compared to controls. Our
      data support the conclusion that the chronic immune activation in HIV-1 infection
      impairs peripheral PDC innate immune responses at least in part via enhanced
      CD40:CD40L interactions.

PMID- 22470496
TI  - Ecological determinants of highly pathogenic avian influenza (H5N1) outbreaks in
      Bangladesh.
AB  - BACKGROUND: The agro-ecology and poultry husbandry of the south Asian and south
      east Asian countries share common features, however, with noticeable differences.
      Hence, the ecological determinants associated with risk of highly pathogenic
      avian influenza (HPAI-H5N1) outbreaks are expected to differ between Bangladesh
      and e.g., Thailand and Vietnam. The primary aim of the current study was to
      establish ecological determinants associated with the risk of HPAI-H5N1 outbreaks
      at subdistrict level in Bangladesh. The secondary aim was to explore the
      performance of two different statistical modeling approaches for unmeasured
      spatially correlated variation. METHODOLOGY/PRINCIPAL FINDINGS: An ecological
      study at subdistrict level in Bangladesh was performed with 138 subdistricts with
      HPAI-H5N1 outbreaks during 2007-2008, and 326 subdistricts with no outbreaks. The
      association between ecological determinants and HPAI-H5N1 outbreaks was examined
      using a generalized linear mixed model. Spatial clustering of the ecological data
      was modeled using 1) an intrinsic conditional autoregressive (ICAR) model at
      subdistrict level considering their first order neighbors, and 2) a multilevel
      (ML) model with subdistricts nested within districts. Ecological determinants
      significantly associated with risk of HPAI-H5N1 outbreaks at subdistrict level
      were migratory birds' staging areas, river network, household density, literacy
      rate, poultry density, live bird markets, and highway network. Predictive risk
      maps were derived based on the resulting models. The resulting models indicate
      that the ML model absorbed some of the covariate effect of the ICAR model because
      of the neighbor structure implied in the two different models.
      CONCLUSIONS/SIGNIFICANCE: The study identified a new set of ecological
      determinants related to river networks, migratory birds' staging areas and
      literacy rate in addition to already known risk factors, and clarified that the
      generalized concept of free grazing duck and duck-rice cultivation interacted
      ecology are not significant determinants for Bangladesh. These findings will
      refine current understanding of the HPAI-H5N1 epidemiology in Bangladesh.

PMID- 22470497
TI  - Crystal structures of the tetratricopeptide repeat domains of kinesin light
      chains: insight into cargo recognition mechanisms.
AB  - Kinesin-1 transports various cargos along the axon by interacting with the cargos
      through its light chain subunit. Kinesin light chains (KLC) utilize its
      tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos.
      Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2
      isoforms exhibit differential binding properties towards some cargos. We
      determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR)
      domains using X-ray crystallography and investigated the different mechanisms by
      which KLCs interact with their cargos. Using isothermal titration calorimetry, we
      attributed the specific interaction between KLC1 and JNK-interacting protein 1
      (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343
      residue is adjacent to other asparagines and lysines, creating a positively
      charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the
      corresponding residue S328 did not interact with JIP1. Based on these finding, we
      propose that N343 of KLC1 can form "a carboxylate clamp" with its neighboring
      asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing
      protein-1's (HOP1) interaction with heat shock proteins. For the binding of
      cargos shared by KLC1 and KLC2, we propose a different site located within the
      groove but not involving N343. We further propose a third binding site on KLC1
      which involves a stretch of polar residues along the inter-TPR loops that may
      form a network of hydrogen bonds to JIP3 and JIP4. Together, these results
      provide structural insights into possible mechanisms of interaction between KLC
      TPR domains and various cargo proteins.

PMID- 22470499
TI  - Housing arrangement and location determine the likelihood of housing loss due to
      wildfire.
AB  - Surging wildfires across the globe are contributing to escalating residential
      losses and have major social, economic, and ecological consequences. The highest
      losses in the U.S. occur in southern California, where nearly 1000 homes per year
      have been destroyed by wildfires since 2000. Wildfire risk reduction efforts
      focus primarily on fuel reduction and, to a lesser degree, on house
      characteristics and homeowner responsibility. However, the extent to which land
      use planning could alleviate wildfire risk has been largely missing from the
      debate despite large numbers of homes being placed in the most hazardous parts of
      the landscape. Our goal was to examine how housing location and arrangement
      affects the likelihood that a home will be lost when a wildfire occurs. We
      developed an extensive geographic dataset of structure locations, including more
      than 5500 structures that were destroyed or damaged by wildfire since 2001, and
      identified the main contributors to property loss in two extensive, fire-prone
      regions in southern California. The arrangement and location of structures
      strongly affected their susceptibility to wildfire, with property loss most
      likely at low to intermediate structure densities and in areas with a history of
      frequent fire. Rates of structure loss were higher when structures were
      surrounded by wildland vegetation, but were generally higher in herbaceous fuel
      types than in higher fuel-volume woody types. Empirically based maps developed
      using housing pattern and location performed better in distinguishing hazardous
      from non-hazardous areas than maps based on fuel distribution. The strong
      importance of housing arrangement and location indicate that land use planning
      may be a critical tool for reducing fire risk, but it will require reliable
      delineations of the most hazardous locations.

PMID- 22470498
TI  - Treatment of mouse limb ischemia with an integrative hypoxia-responsive vector
      expressing the vascular endothelial growth factor gene.
AB  - Constitutive vascular endothelial growth factor (VEGF) gene expression systems
      have been extensively used to treat peripheral arterial diseases, but most of the
      results have not been satisfactory. In this study, we designed a plasmid vector
      with a hypoxia-responsive element sequence incorporated into it with the phiC31
      integrative system (pVHAVI) to allow long-term VEGF gene expression and to be
      activated under hypoxia. Repeated activations of VEGF gene expression under
      hypoxia were confirmed in HEK293 and C2C12 cells transfected with pVHAVI. In limb
      ischemic mice, the local administration of pVHAVI promoted gastrocnemius mass and
      force recovery and ameliorated limb necrosis much better than the group treated
      with hypoxia-insensitive vector, even this last group had produced more VEGF in
      muscle. Histological analyses carried out after four weeks of gene therapy showed
      increased capillary density and matured vessels, and reduced number of necrotic
      cells and fibrosis in pVHAVI treated group. By our study, we demonstrate that the
      presence of high concentration of VEGF in ischemic tissue is not beneficial or is
      less beneficial than maintaining a lower but sufficient and long-term
      concentration of VEGF locally.

PMID- 22470500
TI  - Human infants and baboons show the same pattern of handedness for a communicative
      gesture.
AB  - To test the role of gestures in the origin of language, we studied hand
      preferences for grasping or pointing to objects at several spatial positions in
      human infants and adult baboons. If the roots of language are indeed in gestural
      communication, we expect that human infants and baboons will present a comparable
      difference in their pattern of laterality according to task: both should be more
      right-hand/left-hemisphere specialized when communicating by pointing than when
      simply grasping objects. Our study is the first to test both human infants and
      baboons on the same communicative task. Our results show remarkable convergence
      in the distribution of the two species' hand biases on the two kinds of tasks: In
      both human infants and baboons, right-hand preference was significantly stronger
      for the communicative task than for grasping objects. Our findings support the
      hypothesis that left-lateralized language may be derived from a gestural
      communication system that was present in the common ancestor of baboons and
      humans.

PMID- 22470501
TI  - Saposin C coupled lipid nanovesicles specifically target arthritic mouse joints
      for optical imaging of disease severity.
AB  - Rheumatoid arthritis is a chronic inflammatory disease affecting approximately 1%
      of the population and is characterized by cartilage and bone destruction
      ultimately leading to loss of joint function. Early detection and intervention of
      disease provides the best hope for successful treatment and preservation of joint
      mobility and function. Reliable and non-invasive techniques that accurately
      measure arthritic disease onset and progression are lacking. We recently
      developed a novel agent, SapC-DOPS, which is composed of the membrane-associated
      lysosomal protein saposin C (SapC) incorporated into 1,2-dioleoyl-sn-glycero-3
      phospho-L-serine (DOPS) lipid nanovesicles. SapC-DOPS has a high fusogenic
      affinity for phosphatidylserine-enriched microdomains on surfaces of target cell
      membranes. Incorporation of a far-red fluorophore, CellVue Maroon (CVM), into the
      nanovesicles allows for in vivo non-invasive visualization of the agent in
      targeted tissue. Given that phosphatidylserine is present only on the inner
      leaflet of healthy plasma membranes but is "flipped" to the outer leaflet upon
      cell damage, we hypothesized that SapC-DOPS would target tissue damage associated
      with inflammatory arthritis due to local surface-exposure of phosphatidylserine.
      Optical imaging with SapC-DOPS-CVM in two distinct models of arthritis, serum
      transfer arthritis (e.g., K/BxN) and collagen-induced arthritis (CIA) revealed
      robust SapC-DOPS-CVM specific localization to arthritic paws and joints in live
      animals. Importantly, intensity of localized fluorescent signal correlated with
      macroscopic arthritic disease severity and increased with disease progression.
      Flow cytometry of cells extracted from arthritic joints demonstrated that SapC
      DOPS-CVM localized to an average of 7-8% of total joint cells and primarily to
      CD11b+Gr-1+ cells. Results from the current studies strongly support the
      application of SapC-DOPS-CVM for advanced clinical and research applications
      including: detecting early arthritis onset, assessing disease progression real
      time in live subjects, and providing novel information regarding cell types that
      may mediate arthritis progression within joints.

PMID- 22470502
TI  - Surveillance of airborne adenovirus and Mycoplasma pneumoniae in a hospital
      pediatric department.
AB  - This investigation evaluated the distributions of airborne adenovirus and
      Mycoplasma pneumoniae in public areas in the pediatric department of Children's
      Hospital in northern Taiwan. The airborne viral and bacterial concentrations were
      evaluated twice a week for a year using filter sampling with an airflow rate of
      12 liters per minute for eight hours in the pediatric outpatient department and
      24 hours in the pediatric emergency room. Real-time polymerase chain reaction
      assays were conducted for analysis. Approximately 18% of the air samples from the
      pediatric emergency room were found to contain adenovirus. Approximately forty
      six percent of the air samples from the pediatric outpatient department contained
      Mycoplasma pneumoniae DNA products. High detection rates of airborne adenovirus
      DNA were obtained in July and August in the pediatric public areas. Airborne
      Mycoplasma pneumoniae was detected only in July in the pediatric emergency room
      and the peak levels were found from August to January in the pediatric outpatient
      department. Airborne particles that contained adenovirus and Mycoplasma
      pneumoniae were the most prevalent in the pediatric public areas. The potential
      relationship between these airborne viral/bacterial particles and human infection
      should be examined further.

PMID- 22470503
TI  - Characterization of cholinesterases in plasma of three Portuguese native bird
      species: application to biomonitoring.
AB  - Over the last decades the inhibition of plasma cholinesterase (ChE) activity has
      been widely used as a biomarker to diagnose organophosphate and carbamate
      exposure. Plasma ChE activity is a useful and non-invasive method to monitor bird
      exposure to anticholinesterase compounds; nonetheless several studies had shown
      that the ChE form(s) present in avian plasma may vary greatly among species. In
      order to support further biomonitoring studies and provide reference data for
      wildlife risk-assessment, plasma cholinesterase of the northern gannet (Morus
      bassanus), the white stork (Ciconia ciconia) and the grey heron (Ardea cinerea)
      were characterized using three substrates (acetylthiocholine iodide,
      propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE
      inhibitors (eserine sulphate, BW284C51, and iso-OMPA). Additionally, the range of
      ChE activity that may be considered as basal levels for non-exposed individuals
      was determined. The results suggest that in the plasma of the three species
      studied the main cholinesterase form present is butyrylcholinesterase (BChE).
      Plasma BChE activity in non-exposed individuals was 0.48+/-0.11 SD U/ml, 0.39+/
      0.12 SD U/ml, 0.15+/-0.04 SD U/ml in the northern gannet, white stork and grey
      heron, respectively. These results are crucial for the further use of plasma BChE
      activity in these bird species as a contamination bioindicator of anti
      cholinesterase agents in both wetland and marine environments. Our findings also
      underscore the importance of plasma ChE characterization before its use as a
      biomarker in biomonitoring studies with birds.

PMID- 22470504
TI  - Small molecule antagonists of the Wnt/beta-catenin signaling pathway target
      breast tumor-initiating cells in a Her2/Neu mouse model of breast cancer.
AB  - BACKGROUND: Recent evidence suggests that human breast cancer is sustained by a
      minor subpopulation of breast tumor-initiating cells (BTIC), which confer
      resistance to anticancer therapies and consequently must be eradicated to achieve
      durable breast cancer cure. METHODS/FINDINGS: To identify signaling pathways that
      might be targeted to eliminate BTIC, while sparing their normal stem and
      progenitor cell counterparts, we performed global gene expression profiling of
      BTIC- and mammary epithelial stem/progenitor cell- enriched cultures derived from
      mouse mammary tumors and mammary glands, respectively. Such analyses suggested a
      role for the Wnt/Beta-catenin signaling pathway in maintaining the viability and
      or sustaining the self-renewal of BTICs in vitro. To determine whether the
      Wnt/Beta-catenin pathway played a role in BTIC processes we employed a chemical
      genomics approach. We found that pharmacological inhibitors of Wnt/beta-catenin
      signaling inhibited sphere- and colony-formation by primary breast tumor cells
      and primary mammary epithelial cells, as well as by tumorsphere- and mammosphere
      derived cells. Serial assays of self-renewal in vitro revealed that the Wnt/Beta
      catenin signaling inhibitor PKF118-310 irreversibly affected BTIC, whereas it
      functioned reversibly to suspend the self-renewal of mammary epithelial
      stem/progenitor cells. Incubation of primary tumor cells in vitro with PKF118-310
      eliminated their capacity to subsequently seed tumor growth after transplant into
      syngeneic mice. Administration of PKF118-310 to tumor-bearing mice halted tumor
      growth in vivo. Moreover, viable tumor cells harvested from PKF118-310 treated
      mice were unable to seed the growth of secondary tumors after transplant.
      CONCLUSIONS: These studies demonstrate that inhibitors of Wnt/beta-catenin
      signaling eradicated BTIC in vitro and in vivo and provide a compelling rationale
      for developing such antagonists for breast cancer therapy.

PMID- 22470505
TI  - Loss of genetic diversity means loss of geological information: the endangered
      Japanese crayfish exhibits remarkable historical footprints.
AB  - Intra-specific genetic diversity is important not only because it influences
      population persistence and evolutionary potential, but also because it contains
      past geological, climatic and environmental information. In this paper, we show
      unusually clear genetic structure of the endangered Japanese crayfish that, as a
      sedentary species, provides many insights into lesser-known past environments in
      northern Japan. Over the native range, most populations consisted of unique 16S
      mtDNA haplotypes, resulting in significant genetic divergence (overall F(ST) =
      0.96). Owing to the simple and clear structure, a new graphic approach unraveled
      a detailed evolutionary history; regional crayfish populations were comprised of
      two distinct lineages that had experienced contrasting demographic processes
      (i.e. rapid expansion vs. slow stepwise range expansion) following differential
      drainage topologies and past climate events. Nuclear DNA sequences also showed
      deep separation between the lineages. Current ocean barriers to dispersal did not
      significantly affect the genetic structure of the freshwater crayfish, indicating
      the formation of relatively recent land bridges. This study provides one of the
      best examples of how phylogeographic analysis can unravel a detailed evolutionary
      history of a species and how this history contributes to the understanding of the
      past environment in the region. Ongoing local extinctions of the crayfish lead
      not only to loss of biodiversity but also to the loss of a significant
      information regarding past geological and climatic events.

PMID- 22470506
TI  - Evaluating ecohydrological theories of woody root distribution in the Kalahari.
AB  - The contribution of savannas to global carbon storage is poorly understood, in
      part due to lack of knowledge of the amount of belowground biomass. In these
      ecosystems, the coexistence of woody and herbaceous life forms is often explained
      on the basis of belowground interactions among roots. However, the distribution
      of root biomass in savannas has seldom been investigated, and the dependence of
      root biomass on rainfall regime remains unclear, particularly for woody plants.
      Here we investigate patterns of belowground woody biomass along a rainfall
      gradient in the Kalahari of southern Africa, a region with consistent sandy
      soils. We test the hypotheses that (1) the root depth increases with mean annual
      precipitation (root optimality and plant hydrotropism hypothesis), and (2) the
      root-to-shoot ratio increases with decreasing mean annual rainfall (functional
      equilibrium hypothesis). Both hypotheses have been previously assessed for
      herbaceous vegetation using global root data sets. Our data do not support these
      hypotheses for the case of woody plants in savannas. We find that in the
      Kalahari, the root profiles of woody plants do not become deeper with increasing
      mean annual precipitation, whereas the root-to-shoot ratios decrease along a
      gradient of increasing aridity.

PMID- 22470507
TI  - Oncogenic function of DACT1 in colon cancer through the regulation of beta
      catenin.
AB  - The Wnt/beta-catenin signaling pathway plays important roles in the progression
      of colon cancer. DACT1 has been identified as a modulator of Wnt signaling
      through its interaction with Dishevelled (Dvl), a central mediator of both the
      canonical and noncanonical Wnt pathways. However, the functions of DACT1 in the
      WNT/beta-catenin signaling pathway remain unclear. Here, we present evidence that
      DACT1 is an important positive regulator in colon cancer through regulating the
      stability and sublocation of beta-catenin. We have shown that DACT1 promotes
      cancer cell proliferation in vitro and tumor growth in vivo and enhances the
      migratory and invasive potential of colon cancer cells. Furthermore, the higher
      expression of DACT1 not only increases the nuclear and cytoplasmic fractions of
      beta-catenin, but also increases its membrane-associated fraction. The
      overexpression of DACT1 leads to the increased accumulation of nonphosphorylated
      beta-catenin in the cytoplasm and particularly in the nuclei. We have
      demonstrated that DACT1 interacts with GSK-3beta and beta-catenin. DACT1
      stabilizes beta-catenin via DACT1-induced effects on GSK-3beta and directly
      interacts with beta-catenin proteins. The level of phosphorylated GSK-3beta at
      Ser9 is significantly increased following the elevated expression of DACT1. DACT1
      mediates the subcellular localization of beta-catenin via increasing the level of
      phosphorylated GSK-3beta at Ser9 to inhibit the activity of GSK-3beta. Taken
      together, our study identifies DACT1 as an important positive regulator in colon
      cancer and suggests a potential strategy for the therapeutic control of the beta
      catenin-dependent pathway.

PMID- 22470508
TI  - Differential allocation of constitutive and induced chemical defenses in pine
      tree juveniles: a test of the optimal defense theory.
AB  - Optimal defense theory (ODT) predicts that the within-plant quantitative
      allocation of defenses is not random, but driven by the potential relative
      contribution of particular plant tissues to overall fitness. These predictions
      have been poorly tested on long-lived woody plants. We explored the allocation of
      constitutive and methyl-jasmonate (MJ) inducible chemical defenses in six half
      sib families of Pinus radiata juveniles. Specifically, we studied the
      quantitative allocation of resin and polyphenolics (the two major secondary
      chemicals in pine trees) to tissues with contrasting fitness value (stem phloem,
      stem xylem and needles) across three parts of the plants (basal, middle and
      apical upper part), using nitrogen concentration as a proxy of tissue value.
      Concentration of nitrogen in the phloem, xylem and needles was found to be
      greater higher up the plant. As predicted by the ODT, the same pattern was found
      for the concentration of non-volatile resin in the stem. However, in leaf tissues
      the concentrations of both resin and total phenolics were greater towards the
      base of the plant. Two weeks after MJ application, the concentrations of nitrogen
      in the phloem, resin in the stem and total phenolics in the needles increased by
      roughly 25% compared with the control plants, inducibility was similar across all
      plant parts, and families differed in the inducibility of resin compounds in the
      stem. In contrast, no significant changes were observed either for phenolics in
      the stems, or for resin in the needles after MJ application. Concentration of
      resin in the phloem was double that in the xylem and MJ-inducible, with
      inducibility being greater towards the base of the stem. In contrast, resin in
      the xylem was not MJ-inducible and increased in concentration higher up the
      plant. The pattern of inducibility by MJ-signaling in juvenile P. radiata is
      tissue, chemical-defense and plant-part specific, and is genetically variable.

PMID- 22470509
TI  - Wright's shifting balance theory and the diversification of aposematic signals.
AB  - Despite accumulating evidence for selection within natural systems, the
      importance of random genetic drift opposing Wright's and Fisher's views of
      evolution continue to be a subject of controversy. The geographical
      diversification of aposematic signals appears to be a suitable system to assess
      the factors involved in the process of adaptation since both theories were
      independently proposed to explain this phenomenon. In the present study, the
      effects of drift and selection were assessed from population genetics and
      predation experiments on poison-dart frogs, Ranitomaya imitator, of Northern
      Peru. We specifically focus on the transient zone between two distinct aposematic
      signals. In contrast to regions where high predation maintains a monomorphic
      aposematic signal, the transient zones are characterized by lowered selection and
      a high phenotypic diversity. As a result, the diversification of phenotypes may
      occur via genetic drift without a significant loss of fitness. These new
      phenotypes may then colonize alternative habitats if successfully recognized and
      avoided by predators. This study highlights the interplay between drift and
      selection as determinant processes in the adaptive diversification of aposematic
      signals. Results are consistent with the expectations of the Wright's shifting
      balance theory and represent, to our knowledge, the first empirical demonstration
      of this highly contested theory in a natural system.

PMID- 22470510
TI  - DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual
      regulators of autophagy and transcription.
AB  - Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of
      autophagy and gene transcription. However, the domains or regions of DOR that
      participate in those functions have not been identified. Here we have performed
      structure/function analyses of DOR guided by identification of conserved regions
      in the DOR gene family by phylogenetic reconstructions. We show that DOR is
      present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2,
      and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene
      duplication. In keeping with these data, we show that human TP53INP1 regulates
      autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display
      transcriptional activity. The use of molecular evolutionary information has been
      instrumental to determine the regions that participate in DOR functions. DOR and
      TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28
      42; region 2, 66-112 in human DOR). Mutation of conserved hydrophobic residues in
      region 1 of DOR (that are part of a nuclear export signal, NES) reduces
      transcriptional activity, and blocks nuclear exit and autophagic activity under
      autophagy-activated conditions. We also identify a functional and conserved LC3
      interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of
      conserved acidic residues in region 2 of DOR reduces transcriptional activity,
      impairs nuclear exit in response to autophagy activation, and disrupts autophagy.
      Taken together, our data reveal DOR and TP53INP1 as dual regulators of
      transcription and autophagy, and identify two conserved regions in the DOR family
      that concentrate multiple functions crucial for autophagy and transcription.

PMID- 22470511
TI  - Mathematical modeling of malaria infection with innate and adaptive immunity in
      individuals and agent-based communities.
AB  - BACKGROUND: Agent-based modeling of Plasmodium falciparum infection offers an
      attractive alternative to the conventional Ross-Macdonald methodology, as it
      allows simulation of heterogeneous communities subjected to realistic
      transmission (inoculation patterns). METHODOLOGY/PRINCIPAL FINDINGS: We developed
      a new, agent based model that accounts for the essential in-host processes:
      parasite replication and its regulation by innate and adaptive immunity. The
      model also incorporates a simplified version of antigenic variation by Plasmodium
      falciparum. We calibrated the model using data from malaria-therapy (MT) studies,
      and developed a novel calibration procedure that accounts for a deterministic and
      a pseudo-random component in the observed parasite density patterns. Using the
      parasite density patterns of 122 MT patients, we generated a large number of
      calibrated parameters. The resulting data set served as a basis for constructing
      and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We
      conducted several numerical experiments subjecting AB communities to realistic
      inoculation patterns reported from previous field studies, and compared the model
      output to the observed malaria prevalence in the field. There was overall
      consistency, supporting the potential of this agent-based methodology to
      represent transmission in realistic communities. CONCLUSIONS/SIGNIFICANCE: Our
      approach represents a novel, convenient and versatile method to model Plasmodium
      falciparum infection.

PMID- 22470512
TI  - Mycobacteriophage endolysins: diverse and modular enzymes with multiple catalytic
      activities.
AB  - The mycobacterial cell wall presents significant challenges to mycobacteriophages
      -viruses that infect mycobacterial hosts--because of its unusual structure
      containing a mycolic acid-rich mycobacterial outer membrane attached to an
      arabinogalactan layer that is in turn linked to the peptidoglycan. Although
      little is known about how mycobacteriophages circumvent these barriers during the
      process of infection, destroying it for lysis at the end of their lytic cycles
      requires an unusual set of functions. These include Lysin B proteins that cleave
      the linkage of mycolic acids to the arabinogalactan layer, chaperones required
      for endolysin delivery to peptidoglycan, holins that regulate lysis timing, and
      the endolysins (Lysin As) that hydrolyze peptidoglycan. Because mycobacterial
      peptidoglycan contains atypical features including 3->3 interpeptide linkages, it
      is not surprising that the mycobacteriophage endolysins also have non-canonical
      features. We present here a bioinformatic dissection of these lysins and show
      that they are highly diverse and extensively modular, with an impressive number
      of domain organizations. Most contain three domains with a novel N-terminal
      predicted peptidase, a centrally located amidase, muramidase, or
      transglycosylase, and a C-terminal putative cell wall binding domain.

PMID- 22470513
TI  - Stable isotope composition of fatty acids in organisms of different trophic
      levels in the Yenisei River.
AB  - We studied four-link food chain, periphytic microalgae and water moss
      (producers), trichopteran larvae (consumers I), gammarids (omnivorous--consumers
      II) and Siberian grayling (consumers III) at a littoral site of the Yenisei River
      on the basis of three years monthly sampling. Analysis of bulk carbon stable
      isotopes and compound specific isotope analysis of fatty acids (FA) were done. As
      found, there was a gradual depletion in (13)C contents of fatty acids, including
      essential FA upward the food chain. In all the trophic levels a parabolic
      dependence of delta(13)C values of fatty acids on their degree of
      unsaturation/chain length occurred, with 18:2n-6 and 18:3n-3 in its lowest point.
      The pattern in the delta(13)C differences between individual fatty acids was
      quite similar to that reported in literature for marine pelagic food webs.
      Hypotheses on isotope fractionation were suggested to explain the findings.

PMID- 22470514
TI  - Systemic treatment with CpG-B after sublethal rickettsial infection induces mouse
      death through indoleamine 2,3-dioxygenase (IDO).
AB  - Due to its strong immune stimulatory effects through TLR9, CpG-containing
      oligodeoxynucleotides (CpG ODN) have been tested in multiple clinical trials as
      vaccine adjuvant for infectious diseases and cancer. However, immune suppression
      induced by systemic administration of CpGs has been reported recently. In this
      study, we evaluated the impact of CpGs in an acute rickettsiosis model. We found
      that systemic treatment with type B CpG (CpG-B), but not type A CpG (CpG-A), at 2
      days after sublethal R. australis infection induced mouse death. Although wild
      type (WT) B6 and IDO(-/-) mice showed similar survival rates with three different
      doses of R. australis infection, treatment with CpG-B after sublethal infection
      consistently induced higher mortality with greater tissue bacterial loads in WT
      but not IDO(-/-) mice. Also, CpG-B treatment promoted the development of higher
      serum concentrations of proinflammatory cytokines/chemokines through IDO.
      Furthermore, while T cell-mediated immune responses enhanced by CpG-B were
      independent of IDO, treatment with CpG-B promoted T cell activation, PD-1
      expression and cell apoptosis partially through IDO. A depletion study using anti
      mPDCA-1 mAb indicated that plasmacytoid dendritic cells (pDC) were not required
      for CpG-B-induced death of R. australis-infected mice. Additionally, the results
      in iNOS(-/-) mice suggested that nitric oxide (NO) was partially involved in CpG
      B-induced death of R. australis-infected mice. Surprisingly, pre-treatment with
      CpG-B before administration of a lethal dose of R. australis provided effective
      immunity in WT, IDO(-/-) and iNOS(-/-) mice. Taken together, our study provides
      evidence that CpGs exert complex immunological effects by both IDO-dependent and 
      independent mechanisms, and that systemic treatment with CpGs before or after
      infection has a significant and distinct impact on disease outcomes.

PMID- 22470515
TI  - Convergent, parallel and correlated evolution of trophic morphologies in the
      subfamily schizothoracinae from the Qinghai-Tibetan plateau.
AB  - Schizothoracine fishes distributed in the water system of the Qinghai-Tibetan
      plateau (QTP) and adjacent areas are characterized by being highly adaptive to
      the cold and hypoxic environment of the plateau, as well as by a high degree of
      diversity in trophic morphology due to resource polymorphisms. Although
      convergent and parallel evolution are prevalent in the organisms of the QTP, it
      remains unknown whether similar evolutionary patterns have occurred in the
      schizothoracine fishes. Here, we constructed for the first time a tentative
      molecular phylogeny of the schizothoracine fishes based on the complete sequences
      of the cytochrome b gene. We employed this molecular phylogenetic framework to
      examine the evolution of trophic morphologies. We used Pagel's maximum likelihood
      method to estimate the evolutionary associations of trophic morphologies and food
      resource use. Our results showed that the molecular and published morphological
      phylogenies of Schizothoracinae are partially incongruent with respect to some
      intergeneric relationships. The phylogenetic results revealed that four character
      states of five trophic morphologies and of food resource use evolved at least
      twice during the diversification of the subfamily. State transitions are the
      result of evolutionary patterns including either convergence or parallelism or
      both. Furthermore, our analyses indicate that some characters of trophic
      morphologies in the Schizothoracinae have undergone correlated evolution, which
      are somewhat correlated with different food resource uses. Collectively, our
      results reveal new examples of convergent and parallel evolution in the organisms
      of the QTP. The adaptation to different trophic niches through the modification
      of trophic morphologies and feeding behaviour as found in the schizothoracine
      fishes may account for the formation and maintenance of the high degree of
      diversity and radiations in fish communities endemic to QTP.

PMID- 22470516
TI  - Molecular surveillance of true nontypeable Haemophilus influenzae: an evaluation
      of PCR screening assays.
AB  - BACKGROUND: Unambiguous identification of nontypeable Haemophilus influenzae
      (NTHi) is not possible by conventional microbiology. Molecular characterisation
      of phenotypically defined NTHi isolates suggests that up to 40% are Haemophilus
      haemolyticus (Hh); however, the genetic similarity of NTHi and Hh limits the
      power of simple molecular techniques such as PCR for species discrimination.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we assess the ability of previously
      published and novel PCR-based assays to identify true NTHi. Sixty phenotypic NTHi
      isolates, classified by a dual 16S rRNA gene PCR algorithm as NTHi (n = 22), Hh
      (n = 27) or equivocal (n = 11), were further characterised by sequencing of the
      16S rRNA and recA genes then interrogated by PCR-based assays targeting the omp
      P2, omp P6, lgtC, hpd, 16S rRNA, fucK and iga genes. The sequencing data and PCR
      results were used to define NTHi for this study. Two hpd real time PCR assays
      (hpd#1 and hpd#3) and the conventional iga PCR assay were equally efficient at
      differentiating study-defined NTHi from Hh, each with a receiver operator
      characteristic curve area of 0.90 [0.83; 0.98]. The hpd#1 and hpd#3 assays were
      completely specific against a panel of common respiratory bacteria, unlike the
      iga PCR, and the hpd#3 assay was able to detect below 10 copies per reaction.
      CONCLUSIONS/SIGNIFICANCE: Our data suggest an evolutionary continuum between NTHi
      and Hh and therefore no single gene target could completely differentiate NTHi
      from Hh. The hpd#3 real time PCR assay proved to be the superior method for
      discrimination of NTHi from closely related Haemophilus species with the added
      potential for quantification of H. influenzae directly from specimens. We suggest
      the hpd#3 assay would be suitable for routine NTHi surveillance and to assess the
      impact of antibiotics and vaccines, on H. influenzae carriage rates, carriage
      density, and disease.

PMID- 22470517
TI  - Normalisation to blood activity is required for the accurate quantification of
      Na/I symporter ectopic expression by SPECT/CT in individual subjects.
AB  - The utilisation of the Na/I symporter (NIS) and associated radiotracers as a
      reporter system for imaging gene expression is now reaching the clinical setting
      in cancer gene therapy applications. However, a formal assessment of the
      methodology in terms of normalisation of the data still remains to be performed,
      particularly in the context of the assessment of activities in individual
      subjects in longitudinal studies. In this context, we administered to mice a
      recombinant, replication-incompetent adenovirus encoding rat NIS, or a human
      colorectal carcinoma cell line (HT29) encoding mouse NIS. We used (99m)Tc
      pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of
      ectopic NIS expression in longitudinal kinetic studies. Some animals of the
      cohort were culled and NIS expression was measured by quantitative RT-PCR and
      immunohistochemistry. The radioactive content of some liver biopsies was also
      measured ex vivo. Our results show that in longitudinal studies involving
      datasets taken from individual mice, the presentation of non-normalised data
      (activity expressed as %ID/g or %ID/cc) leads to 'noisy', and sometimes
      incoherent, results. This variability is due to the fact that the blood
      pertechnetate concentration can vary up to three-fold from day to day.
      Normalisation of these data with blood activities corrects for these
      inconsistencies. We advocate that, blood pertechnetate activity should be
      determined and used to normalise the activity measured in the organ/region of
      interest that expresses NIS ectopically. Considering that NIS imaging has already
      reached the clinical setting in the context of cancer gene therapy, this
      normalisation may be essential in order to obtain accurate and predictive
      information in future longitudinal clinical studies in biotherapy.

PMID- 22470518
TI  - The impact of weather on influenza and pneumonia mortality in New York City, 1975
      2002: a retrospective study.
AB  - The substantial winter influenza peak in temperate climates has lead to the
      hypothesis that cold and/or dry air is a causal factor in influenza variability.
      We examined the relationship between cold and/or dry air and daily influenza and
      pneumonia mortality in the cold season in the New York metropolitan area from
      1975-2002. We conducted a retrospective study relating daily pneumonia and
      influenza mortality for New York City and surroundings from 1975-2002 to daily
      air temperature, dew point temperature (a measure of atmospheric humidity), and
      daily air mass type. We identified high mortality days and periods and employed
      temporal smoothers and lags to account for the latency period and the time
      between infection and death. Unpaired t-tests were used to compare high mortality
      events to non-events and nonparametric bootstrapped regression analysis was used
      to examine the characteristics of longer mortality episodes. We found a
      statistically significant (p = 0.003) association between periods of low dew
      point temperature and above normal pneumonia and influenza mortality 17 days
      later. The duration (r = -0.61) and severity (r = -0.56) of high mortality
      episodes was inversely correlated with morning dew point temperature prior to and
      during the episodes. Weeks in which moist polar air masses were common (air
      masses characterized by low dew point temperatures) were likewise followed by
      above normal mortality 17 days later (p = 0.019). This research supports the
      contention that cold, dry air may be related to influenza mortality and suggests
      that warning systems could provide enough lead time to be effective in mitigating
      the effects.

PMID- 22470519
TI  - HLA-B27 modulates intracellular growth of Salmonella pathogenicity island 2
      mutants and production of cytokines in infected monocytic U937 cells.
AB  - BACKGROUND: Salmonella enterica serovar Enteritidis PT4 KS8822/88 replicates
      rapidly in HLA-B27-transfected human monocytic U937 cells. In this process,
      Salmonella pathogenicity island 2 (SPI-2) genes play a crucial role. Our previous
      study indicated that 118 Salmonella genes, including 8 SPI-2 genes were affected
      by HLA-B27 antigen during Salmonella infection of U937 cells. METHODS/PRINCIPAL
      FINDINGS: To further investigate Salmonella replication in HLA-B27-positive U937
      monocytic cells, two SPI-2 genes, ssaS and sscA up-regulated most during
      Salmonella infection of HLA-B27-transfected U937 cells, were mutated by using one
      step gene disruption method. Intracellular survival and replication of the
      mutants in the U937 cells was compared to that of the wild type strain.
      Surprisingly, the two mutated strains replicated significantly more than the wild
      type bacteria in HLA-B27-transfected cells. Secretion of tumor necrosis factor
      alpha (TNF-alpha) and interleukin 10 (IL-10) was significantly induced during the
      infection of HLA-B27-transfected U937 cells with the mutants. The results
      indicated that the certain SPI-2 genes in wild type bacteria suppress Salmonella
      intracellular growth and production of cytokines in infected HLA-B27-transfected
      cells. HLA-B27-associated modulation of Salmonella SPI-2 genes and cytokine
      production may have importance in the persistent infection of the bacteria and
      the pathogenesis of reactive arthritis. CONCLUSIONS: The study provides evidence
      that certain virulence factors of pathogens can reduce the intracellular growth
      in the host cells. We suggest that the limiting intracellular growth might be a
      strategy for persistence of bacteria in host cells, keeping a balance between
      pathogenic growth and pathogenesis.

PMID- 22470520
TI  - Reassessment of the evidence for postcranial skeletal pneumaticity in Triassic
      archosaurs, and the early evolution of the avian respiratory system.
AB  - Uniquely among extant vertebrates, birds possess complex respiratory systems
      characterised by the combination of small, rigid lungs, extensive pulmonary air
      sacs that possess diverticula that invade (pneumatise) the postcranial skeleton,
      unidirectional ventilation of the lungs, and efficient crosscurrent gas exchange.
      Crocodilians, the only other living archosaurs, also possess unidirectional lung
      ventilation, but lack true air sacs and postcranial skeletal pneumaticity (PSP).
      PSP can be used to infer the presence of avian-like pulmonary air sacs in several
      extinct archosaur clades (non-avian theropod dinosaurs, sauropod dinosaurs and
      pterosaurs). However, the evolution of respiratory systems in other archosaurs,
      especially in the lineage leading to crocodilians, is poorly documented. Here, we
      use uCT-scanning to investigate the vertebral anatomy of Triassic archosaur taxa,
      from both the avian and crocodilian lineages as well as non-archosaurian diapsid
      outgroups. Our results confirm previous suggestions that unambiguous evidence of
      PSP (presence of internal pneumatic cavities linked to the exterior by foramina)
      is found only in bird-line (ornithodiran) archosaurs. We propose that pulmonary
      air sacs were present in the common ancestor of Ornithodira and may have been
      subsequently lost or reduced in some members of the clade (notably in
      ornithischian dinosaurs). The development of these avian-like respiratory
      features might have been linked to inferred increases in activity levels among
      ornithodirans. By contrast, no crocodile-line archosaur (pseudosuchian) exhibits
      evidence for unambiguous PSP, but many of these taxa possess the complex array of
      vertebral laminae and fossae that always accompany the presence of air sacs in
      ornithodirans. These laminae and fossae are likely homologous with those in
      ornithodirans, which suggests the need for further investigation of the
      hypothesis that a reduced, or non-invasive, system of pulmonary air sacs may be
      have been present in these taxa (and secondarily lost in extant crocodilians) and
      was potentially primitive for Archosauria as a whole.

PMID- 22470522
TI  - Multifractal spatial patterns and diversity in an ecological succession.
AB  - We analyzed the relationship between biodiversity and spatial biomass
      heterogeneity along an ecological succession developed in the laboratory.
      Periphyton (attached microalgae) biomass spatial patterns at several successional
      stages were obtained using digital image analysis and at the same time we
      estimated the species composition and abundance. We show that the spatial pattern
      was self-similar and as the community developed in an homogeneous environment the
      pattern is self-organized. To characterize it we estimated the multifractal
      spectrum of generalized dimensions D(q). Using D(q) we analyze the existence of
      cycles of heterogeneity during succession and the use of the information
      dimension D(1) as an index of successional stage. We did not find cycles but the
      values of D(1) showed an increasing trend as the succession developed and the
      biomass was higher. D(1) was also negatively correlated with Shannon's diversity.
      Several studies have found this relationship in different ecosystems but here we
      prove that the community self-organizes and generates its own spatial
      heterogeneity influencing diversity. If this is confirmed with more experimental
      and theoretical evidence D(1) could be used as an index, easily calculated from
      remote sensing data, to detect high or low diversity areas.

PMID- 22470521
TI  - Amyloid precursor protein (APP) mediated regulation of ganglioside homeostasis
      linking Alzheimer's disease pathology with ganglioside metabolism.
AB  - Gangliosides are important players for controlling neuronal function and are
      directly involved in AD pathology. They are among the most potent stimulators of
      Abeta production, are enriched in amyloid plaques and bind amyloid beta (Abeta).
      However, the molecular mechanisms linking gangliosides with AD are unknown. Here
      we identified the previously unknown function of the amyloid precursor protein
      (APP), specifically its cleavage products Abeta and the APP intracellular domain
      (AICD), of regulating GD3-synthase (GD3S). Since GD3S is the key enzyme
      converting a- to b-series gangliosides, it therefore plays a major role in
      controlling the levels of major brain gangliosides. This regulation occurs by two
      separate and additive mechanisms. The first mechanism directly targets the
      enzymatic activity of GD3S: Upon binding of Abeta to the ganglioside GM3, the
      immediate substrate of the GD3S, enzymatic turnover of GM3 by GD3S was strongly
      reduced. The second mechanism targets GD3S expression. APP cleavage results, in
      addition to Abeta release, in the release of AICD, a known candidate for gene
      transcriptional regulation. AICD strongly down regulated GD3S transcription and
      knock-in of an AICD deletion mutant of APP in vivo, or knock-down of Fe65 in
      neuroblastoma cells, was sufficient to abrogate normal GD3S functionality.
      Equally, knock-out of the presenilin genes, presenilin 1 and presenilin 2,
      essential for Abeta and AICD production, or of APP itself, increased GD3S
      activity and expression and consequently resulted in a major shift of a- to b
      series gangliosides. In addition to GD3S regulation by APP processing,
      gangliosides in turn altered APP cleavage. GM3 decreased, whereas the ganglioside
      GD3, the GD3S product, increased Abeta production, resulting in a regulatory
      feedback cycle, directly linking ganglioside metabolism with APP processing and
      Abeta generation. A central aspect of this homeostatic control is the reduction
      of GD3S activity via an Abeta-GM3 complex and AICD-mediated repression of GD3S
      transcription.

PMID- 22470523
TI  - Peptides of the constant region of antibodies display fungicidal activity.
AB  - Synthetic peptides with sequences identical to fragments of the constant region
      of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a
      fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans,
      Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including
      caspofungin and triazole resistant strains. Alanine-substituted derivatives of
      fungicidal Fc-peptides, tested to evaluate the critical role of each residue,
      displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc
      peptide, included in all human IgGs, displayed a therapeutic effect against
      experimental mucosal and systemic candidiasis in mouse models. It is intriguing
      to hypothesize that some Fc-peptides may influence the antifungal immune response
      and constitute the basis for devising new antifungal agents.

PMID- 22470524
TI  - Increased sleep fragmentation leads to impaired off-line consolidation of motor
      memories in humans.
AB  - A growing literature supports a role for sleep after training in long-term memory
      consolidation and enhancement. Consequently, interrupted sleep should result in
      cognitive deficits. Recent evidence from an animal study indeed showed that
      optimal memory consolidation during sleep requires a certain amount of
      uninterrupted sleep. Sleep continuity is disrupted in various medical disorders.
      We compared performance on a motor sequence learning task (MST) in relatively
      young subjects with obstructive sleep apnea (n = 16; apnea-hypopnea index 17.1+/
      2.6/h [SEM]) to a carefully matched control group (n = 15, apnea-hypopnea index
      3.7+/-0.4/h, p<0.001. Apart from AHI, oxygen nadir and arousal index, there were
      no significant differences between groups in total sleep time, sleep efficiency
      and sleep architecture as well as subjective measures of sleepiness based on
      standard questionnaires. In addition performance on the psychomotor vigilance
      task (reaction time and lapses), which is highly sensitive to sleep deprivation
      showed no differences as well as initial learning performance during the training
      phase. However there was a significant difference in the primary outcome of
      immediate overnight improvement on the MST between the two groups (controls =
      14.7+/-4%, patients = 1.1+/-3.6%; P = 0.023) as well as plateau performance
      (controls = 24.0+/-5.3%, patients = 10.1+/-2.0%; P = 0.017) and this difference
      was predicted by the arousal index (p = 0.02) rather than oxygen saturation
      (nadir and time below 90% saturation. Taken together, this outcome provides
      evidence that there is a clear minimum requirement of sleep continuity in humans
      to ensure optimal sleep dependent memory processes. It also provides important
      new information about the cognitive impact of obstructive sleep apnea and
      challenges its current definitions.

PMID- 22470525
TI  - HDL proteome in hemodialysis patients: a quantitative nanoflow liquid
      chromatography-tandem mass spectrometry approach.
AB  - Aside from a decrease in the high-density lipoprotein (HDL) cholesterol levels,
      qualitative abnormalities of HDL can contribute to an increase in cardiovascular
      (CV) risk in end-stage renal disease (ESRD) patients undergoing chronic
      hemodialysis (HD). Dysfunctional HDL leads to an alteration of reverse
      cholesterol transport and the antioxidant and anti-inflammatory properties of
      HDL. In this study, a quantitative proteomics approach, based on iTRAQ labeling
      and nanoflow liquid chromatography mass spectrometry analysis, was used to
      generate detailed data on HDL-associated proteins. The HDL composition was
      compared between seven chronic HD patients and a pool of seven healthy controls.
      To confirm the proteomics results, specific biochemical assays were then
      performed in triplicate in the 14 samples as well as 46 sex-matched independent
      chronic HD patients and healthy volunteers. Of the 122 proteins identified in the
      HDL fraction, 40 were differentially expressed between the healthy volunteers and
      the HD patients. These proteins are involved in many HDL functions, including
      lipid metabolism, the acute inflammatory response, complement activation, the
      regulation of lipoprotein oxidation, and metal cation homeostasis. Among the
      identified proteins, apolipoprotein C-II and apolipoprotein C-III were
      significantly increased in the HDL fraction of HD patients whereas
      serotransferrin was decreased. In this study, we identified new markers of
      potential relevance to the pathways linked to HDL dysfunction in HD. Proteomic
      analysis of the HDL fraction provides an efficient method to identify new and
      uncharacterized candidate biomarkers of CV risk in HD patients.

PMID- 22470526
TI  - Chlamydia trachomatis test-of-cure cannot be based on a single highly sensitive
      laboratory test taken at least 3 weeks after treatment.
AB  - Current test-of-cure practice in patients with Chlamydia trachomatis (Ct)
      infection is to confirm cure with a single test taken at least 3 weeks after
      treatment. Effectiveness of single-time-point testing however lacks a scientific
      evidence basis and the high sensitivity of laboratory assays nowadays in use for
      this purpose may compromise the clinical significance of their results.
      Prospectively following 59 treated Ct infections, administering care as usual,
      the presence of Ct plasmid DNA and rRNA was systematically assessed by multiple
      time-sequential measurements, i.e. on 18 samples taken per patient during 8 weeks
      following treatment with a single dose of 1000 mg Azythromycin. A high proportion
      (42%) of Ct infections tested positive on at least one of the samples taken after
      3 weeks. Patients' test results showed substantial inter-individual and intra
      individual variation over time and by type of NAAT used. We demonstrated frequent
      intermittent positive patterns in Ct test results over time, and strongly argue
      against current test-of-cure practice.

PMID- 22470527
TI  - Biological properties of solid free form designed ceramic scaffolds with BMP-2:
      in vitro and in vivo evaluation.
AB  - Porous ceramic scaffolds are widely studied in the tissue engineering field due
      to their potential in medical applications as bone substitutes or as bone-filling
      materials. Solid free form (SFF) fabrication methods allow fabrication of ceramic
      scaffolds with fully controlled pore architecture, which opens new perspectives
      in bone tissue regeneration materials. However, little experimentation has been
      performed about real biological properties and possible applications of SFF
      designed 3D ceramic scaffolds. Thus, here the biological properties of a specific
      SFF scaffold are evaluated first, both in vitro and in vivo, and later scaffolds
      are also implanted in pig maxillary defect, which is a model for a possible
      application in maxillofacial surgery. In vitro results show good biocompatibility
      of the scaffolds, promoting cell ingrowth. In vivo results indicate that material
      on its own conducts surrounding tissue and allow cell ingrowth, thanks to the
      designed pore size. Additional osteoinductive properties were obtained with BMP
      2, which was loaded on scaffolds, and optimal bone formation was observed in pig
      implantation model. Collectively, data show that SFF scaffolds have real
      application possibilities for bone tissue engineering purposes, with the main
      advantage of being fully customizable 3D structures.

PMID- 22470528
TI  - Prediction of muscle energy states at low metabolic rates requires feedback
      control of mitochondrial respiratory chain activity by inorganic phosphate.
AB  - The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux
      in skeletal muscle was investigated. Hypotheses of key control mechanisms were
      included in a biophysical model of oxidative phosphorylation and tested against
      metabolite dynamics recorded by (31)P nuclear magnetic resonance spectroscopy
      ((31)P MRS). Simulations of the initial model featuring only ADP and Pi feedback
      control of flux failed in reproducing the experimentally sampled relation between
      myoplasmic free energy of ATP hydrolysis (DeltaG(p) = DeltaG(p)(o')+RT ln
      ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (<0.2
      mM/s). Model analyses including Monte Carlo simulation approaches and metabolic
      control analysis (MCA) showed that this problem could not be amended by model re
      parameterization, but instead required reformulation of ADP and Pi feedback
      control or introduction of additional control mechanisms (feed forward
      activation), specifically at respiratory Complex III. Both hypotheses were
      implemented and tested against time course data of phosphocreatine (PCr), Pi and
      ATP dynamics during post-exercise recovery and validation data obtained by (31)P
      MRS of sedentary subjects and track athletes. The results rejected the hypothesis
      of regulation by feed forward activation. Instead, it was concluded that feedback
      control of respiratory chain complexes by inorganic phosphate is essential to
      explain the regulation of mitochondrial ATP synthesis flux in skeletal muscle
      throughout its full dynamic range.

PMID- 22470529
TI  - beta-Cells with relative low HIMP1 overexpression levels in a transgenic mouse
      line enhance basal insulin production and hypoxia/hypoglycemia tolerance.
AB  - Rodent pancreatic beta-cells that naturally lack hypoglycemia/hypoxia inducible
      mitochondrial protein 1 (HIMP1) are susceptible to hypoglycemia and hypoxia
      influences. A linkage between the hypoglycemia/hypoxia susceptibility and the
      lack of HIMP1 is suggested in a recent study using transformed beta-cells lines.
      To further illuminate this linkage, we applied mouse insulin 1 gene promoter
      (MIP) to control HIMP1-a isoform cDNA and have generated three lines (L1 to L3)
      of heterozygous HIMP1 transgenic (Tg) mice by breeding of three founders with
      C57BL/6J mice. In HIMP1-Tg mice/islets, we performed quantitative polymerase
      chain reaction (PCR), immunoblot, histology, and physiology studies to
      investigate HIMP1 overexpression and its link to beta-cell function/survival and
      body glucose homeostasis. We found that the HIMP1 level increased steadily in
      beta-cells of L1 to L3 heterozygous HIMP1-Tg mice. HIMP1 overexpression at
      relatively lower levels in L1 heterozygotes results in a negligible decline in
      blood glucose concentrations and an insignificant elevation in blood insulin
      levels, while HIMP1 overexpression at higher levels are toxic, causing
      hyperglycemia in L2/3 heterozygotes. Follow-up studies in 5-30-week-old L1
      heterozygous mice/islets found that HIMP1 overexpression at relatively lower
      levels in beta-cells has enhanced basal insulin biosynthesis, basal insulin
      secretion, and tolerances to low oxygen/glucose influences. The findings enforced
      the linkage between the hypoglycemia/hypoxia susceptibility and the lack of HIMP1
      in beta-cells, and show a potential value of HIMP1 overexpression at relatively
      lower levels in modulating beta-cell function and survival.

PMID- 22470530
TI  - Design of a bovine low-density SNP array optimized for imputation.
AB  - The Illumina BovineLD BeadChip was designed to support imputation to higher
      density genotypes in dairy and beef breeds by including single-nucleotide
      polymorphisms (SNPs) that had a high minor allele frequency as well as uniform
      spacing across the genome except at the ends of the chromosome where densities
      were increased. The chip also includes SNPs on the Y chromosome and mitochondrial
      DNA loci that are useful for determining subspecies classification and certain
      paternal and maternal breed lineages. The total number of SNPs was 6,909.
      Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip
      was over 97% for most dairy and beef populations. The BovineLD imputations were
      about 3 percentage points more accurate than those from the Illumina GoldenGate
      Bovine3K BeadChip across multiple populations. The improvement was greatest when
      neither parent was genotyped. The minor allele frequencies were similar across
      taurine beef and dairy breeds as was the proportion of SNPs that were
      polymorphic. The new BovineLD chip should facilitate low-cost genomic selection
      in taurine beef and dairy cattle.

PMID- 22470531
TI  - Characterization of the proteostasis roles of glycerol accumulation, protein
      degradation and protein synthesis during osmotic stress in C. elegans.
AB  - Exposure of C. elegans to hypertonic stress-induced water loss causes rapid and
      widespread cellular protein damage. Survival in hypertonic environments depends
      critically on the ability of worm cells to detect and degrade misfolded and
      aggregated proteins. Acclimation of C. elegans to mild hypertonic stress
      suppresses protein damage and increases survival under more extreme hypertonic
      conditions. Suppression of protein damage in acclimated worms could be due to 1)
      accumulation of the chemical chaperone glycerol, 2) upregulation of protein
      degradation activity, and/or 3) increases in molecular chaperoning capacity of
      the cell. Glycerol and other chemical chaperones are widely thought to protect
      proteins from hypertonicity-induced damage. However, protein damage is unaffected
      by gene mutations that inhibit glycerol accumulation or that cause dramatic
      constitutive elevation of glycerol levels. Pharmacological or RNAi inhibition of
      proteasome and lyosome function and measurements of cellular protein degradation
      activity demonstrated that upregulation of protein degradation mechanisms plays
      no role in acclimation. Thus, changes in molecular chaperone capacity must be
      responsible for suppressing protein damage in acclimated worms. Transcriptional
      changes in chaperone expression have not been detected in C. elegans exposed to
      hypertonic stress. However, acclimation to mild hypertonicity inhibits protein
      synthesis 50-70%, which is expected to increase chaperone availability for coping
      with damage to existing proteins. Consistent with this idea, we found that RNAi
      silencing of essential translational components or acute exposure to
      cycloheximide results in a 50-80% suppression of hypertonicity-induced
      aggregation of polyglutamine-YFP (Q35::YFP). Dietary changes that increase
      protein production also increase Q35::YFP aggregation 70-180%. Our results
      demonstrate directly for the first time that inhibition of protein translation
      protects extant proteins from damage brought about by an environmental stressor,
      demonstrate important differences in aging- versus stress-induced protein damage,
      and challenge the widely held view that chemical chaperones are accumulated
      during hypertonic stress to protect protein structure/function.

PMID- 22470532
TI  - Neuronal profilin isoforms are addressed by different signalling pathways.
AB  - Profilins are prominent regulators of actin dynamics. While most mammalian cells
      express only one profilin, two isoforms, PFN1 and PFN2a are present in the CNS.
      To challenge the hypothesis that the expression of two profilin isoforms is
      linked to the complex shape of neurons and to the activity-dependent structural
      plasticity, we analysed how PFN1 and PFN2a respond to changes of neuronal
      activity. Simultaneous labelling of rodent embryonic neurons with isoform
      specific monoclonal antibodies revealed both isoforms in the same synapse.
      Immunoelectron microscopy on brain sections demonstrated both profilins in
      synapses of the mature rodent cortex, hippocampus and cerebellum. Both isoforms
      were significantly more abundant in postsynaptic than in presynaptic structures.
      Immunofluorescence showed PFN2a associated with gephyrin clusters of the
      postsynaptic active zone in inhibitory synapses of embryonic neurons. When
      cultures were stimulated in order to change their activity level, active synapses
      that were identified by the uptake of synaptotagmin antibodies, displayed
      significantly higher amounts of both isoforms than non-stimulated controls.
      Specific inhibition of NMDA receptors by the antagonist APV in cultured rat
      hippocampal neurons resulted in a decrease of PFN2a but left PFN1 unaffected.
      Stimulation by the brain derived neurotrophic factor (BDNF), on the other hand,
      led to a significant increase in both synaptic PFN1 and PFN2a. Analogous results
      were obtained for neuronal nuclei: both isoforms were localized in the same
      nucleus, and their levels rose significantly in response to KCl stimulation,
      whereas BDNF caused here a higher increase in PFN1 than in PFN2a. Our results
      strongly support the notion of an isoform specific role for profilins as
      regulators of actin dynamics in different signalling pathways, in excitatory as
      well as in inhibitory synapses. Furthermore, they suggest a functional role for
      both profilins in neuronal nuclei.

PMID- 22470533
TI  - Interbasin water transfer, riverine connectivity, and spatial controls on fish
      biodiversity.
AB  - BACKGROUND: Large-scale inter-basin water transfer (IBWT) projects are commonly
      proposed as solutions to water distribution and supply problems. These problems
      are likely to intensify under future population growth and climate change
      scenarios. Scarce data on the distribution of freshwater fishes frequently limits
      the ability to assess the potential implications of an IBWT project on freshwater
      fish communities. Because connectivity in habitat networks is expected to be
      critical to species' biogeography, consideration of changes in the relative
      isolation of riverine networks may provide a strategy for controlling impacts of
      IBWTs on freshwater fish communities. METHODS/PRINCIPAL FINDINGS: Using empirical
      data on the current patterns of freshwater fish biodiversity for rivers of
      peninsular India, we show here how the spatial changes alone under an archetypal
      IBWT project will (1) reduce freshwater fish biodiversity system-wide, (2) alter
      patterns of local species richness, (3) expand distributions of widespread
      species throughout peninsular rivers, and (4) decrease community richness by
      increasing inter-basin similarity (a mechanism for the observed decrease in
      biodiversity). Given the complexity of the IBWT, many paths to partial or full
      completion of the project are possible. We evaluate two strategies for step-wise
      implementation of the 11 canals, based on economic or ecological considerations.
      We find that for each step in the project, the impacts on freshwater fish
      communities are sensitive to which canal is added to the network.
      CONCLUSIONS/SIGNIFICANCE: Importantly, ecological impacts can be reduced by
      associating the sequence in which canals are added to characteristics of the
      links, except for the case when all 11 canals are implemented simultaneously (at
      which point the sequence of canal addition is inconsequential). By identifying
      the fundamental relationship between the geometry of riverine networks and
      freshwater fish biodiversity, our results will aid in assessing impacts of IBWT
      projects and balancing ecosystem and societal demands for freshwater, even in
      cases where biodiversity data are limited.

PMID- 22470534
TI  - Monitoring the size and lateral dynamics of ErbB1 enriched membrane domains
      through live cell plasmon coupling microscopy.
AB  - To illuminate the role of the spatial organization of the epidermal growth factor
      receptor (ErbB1) in signal transduction quantitative information about the
      receptor topography on the cell surface, ideally on living cells and in real
      time, are required. We demonstrate that plasmon coupling microscopy (PCM) enables
      to detect, size, and track individual membrane domains enriched in ErbB1 with
      high temporal resolution. We used a dendrimer enhanced labeling strategy to label
      ErbB1 receptors on epidermoid carcinoma cells (A431) with 60 nm Au nanoparticle
      (NP) immunolabels under physiological conditions at 37 degrees C. The statistical
      analysis of the spatial NP distribution on the cell surface in the scanning
      electron microscope (SEM) confirmed a clustering of the NP labels consistent with
      a heterogeneous distribution of ErbB1 in the plasma membrane. Spectral shifts in
      the scattering response of clustered NPs facilitated the detection and sizing of
      individual NP clusters on living cells in solution in an optical microscope. We
      tracked the lateral diffusion of individual clusters at a frame rate of 200
      frames/s while simultaneously monitoring the configurational dynamics of the
      clusters. Structural information about the NP clusters in their membrane
      confinements were obtained through analysis of the electromagnetic coupling of
      the co-confined NP labels through polarization resolved PCM. Our studies show
      that the ErbB1 receptor is enriched in membrane domains with typical diameters in
      the range between 60-250 nm. These membrane domains exhibit a slow lateral
      diffusion with a diffusion coefficient of D = |0.0054+/-0.0064| um(2)/s, which is
      almost an order of magnitude slower than the mean diffusion coefficient of
      individual NP tagged ErbB1 receptors under identical conditions.

PMID- 22470535
TI  - S100A9 interaction with TLR4 promotes tumor growth.
AB  - By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring
      the appearance of palpable tumors we observed a delayed tumor growth in animals
      devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed
      in normal prostate tissue from control C57BL/6 mice but were readily detected in
      TRAMP prostate tumors. Also, S100A9 expression was observed in association with
      CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of
      TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL
      4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/
      ), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When
      expression of immune-regulating genes was analyzed using RT-PCR the only common
      change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFbeta
      expression in splenic CD11b(+) cells. Lastly, treatment of mice with a small
      molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor
      growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in
      two different tumor models and pharmacological inhibition of S100A9-TLR4
      interactions is a novel and promising target for anti-tumor therapies.

PMID- 22470536
TI  - DR(high+)CD45RA(-)-Tregs potentially affect the suppressive activity of the total
      Treg pool in renal transplant patients.
AB  - Recent studies show that regulatory T cells (Tregs) play an essential role in
      tolerance induction after organ transplantation. In order to examine whether
      there are differences in the composition of the total CD4(+)CD127(low+/-)FoxP3(+)
      Treg cell pool between stable transplant patients and patients with biopsy
      proven rejection (BPR), we compared the percentages and the functional activity
      of the different Treg cell subsets (DR(high+)CD45RA(-)-Tregs, DR(low+)CD45RA(-)
      Tregs, DR(-)CD45RA(-)-Tregs, DR(-)CD45RA(+)-Tregs). All parameters were
      determined during the three different periods of time after transplantation (0-30
      days, 31-1,000 days, >1,000 days). Among 156 transplant patients, 37 patients
      suffered from BPR. The most prominent differences between rejecting and non
      rejecting patients were observed regarding the DR(high+)CD45RA(-)-Treg cell
      subset. Our data demonstrate that the suppressive activity of the total Treg pool
      strongly depends on the presence of these Treg cells. Their percentage within the
      total Treg pool strongly decreased after transplantation and remained relatively
      low during the first year after transplantation in all patients. Subsequently,
      the proportion of this Treg subset increased again in patients who accepted the
      transplant and reached a value of healthy non-transplanted subjects. By contrast,
      in patients with acute kidney rejection, the DR(high+)CD45RA(-)-Treg subset
      disappeared excessively, causing a reduction in the suppressive activity of the
      total Treg pool. Therefore, both the monitoring of its percentage within the
      total Treg pool and the monitoring of the HLA-DR MFI of the DR(+)CD45RA(-)-Treg
      subset may be useful tools for the prediction of graft rejection.

PMID- 22470537
TI  - Analysis of clonal type-specific antibody reactions in Toxoplasma gondii
      seropositive humans from Germany by peptide-microarray.
AB  - BACKGROUND: Different clonal types of Toxoplasma gondii are thought to be
      associated with distinct clinical manifestations of infections. Serotyping is a
      novel technique which may allow to determine the clonal type of T. gondii humans
      are infected with and to extend typing studies to larger populations which
      include infected but non-diseased individuals. METHODOLOGY: A peptide-microarray
      test for T. gondii serotyping was established with 54 previously published
      synthetic peptides, which mimic clonal type-specific epitopes. The test was
      applied to human sera (n = 174) collected from individuals with an acute T.
      gondii infection (n = 21), a latent T. gondii infection (n = 53) and from T.
      gondii-seropositive forest workers (n = 100). FINDINGS: The majority (n = 124;
      71%) of all T. gondii seropositive human sera showed reactions against synthetic
      peptides with sequences specific for clonal type II (type II peptides). Type I
      and type III peptides were recognized by 42% (n = 73) or 16% (n = 28) of the
      human sera, respectively, while type II-III, type I-III or type I-II peptides
      were recognized by 49% (n = 85), 36% (n = 62) or 14% (n = 25) of the sera,
      respectively. Highest reaction intensities were observed with synthetic peptides
      mimicking type II-specific epitopes. A proportion of the sera (n = 22; 13%)
      showed no reaction with type-specific peptides. Individuals with acute
      toxoplasmosis reacted with a statistically significantly higher number of
      peptides as compared to individuals with latent T. gondii infection or
      seropositive forest workers. CONCLUSIONS: Type II-specific reactions were
      overrepresented and higher in intensity in the study population, which was in
      accord with genotyping studies on T. gondii oocysts previously conducted in the
      same area. There were also individuals with type I- or type III-specific
      reactions. Well-characterized reference sera and further specific peptide markers
      are needed to establish and to perform future serotyping approaches with higher
      resolution.

PMID- 22470538
TI  - Harvesting electricity with Geobacter bremensis isolated from compost.
AB  - Electrochemically active (EA) biofilms were formed on metallic dimensionally
      stable anode-type electrode (DSA), embedded in garden compost and polarized at
      +0.50 V/SCE. Analysis of 16S rRNA gene libraries revealed that biofilms were
      heavily enriched in Deltaproteobacteria in comparison to control biofilms formed
      on non-polarized electrodes, which were preferentially composed of
      Gammaproteobacteria and Firmicutes. Among Deltaproteobacteria, sequences
      affiliated with Pelobacter and Geobacter genera were identified. A bacterial
      consortium was cultivated, in which 25 isolates were identified as Geobacter
      bremensis. Pure cultures of 4 different G. bremensis isolates gave higher current
      densities (1400 mA/m(2) on DSA, 2490 mA/m(2) on graphite) than the original multi
      species biofilms (in average 300 mA/m(2) on DSA) and the G. bremensis DSM type
      strain (100-300 A/m(2) on DSA; 2485 mA/m(2) on graphite). FISH analysis confirmed
      that G. bremensis represented a minor fraction in the original EA biofilm, in
      which species related to Pelobacter genus were predominant. The Pelobacter type
      strain did not show EA capacity, which can explain the lower performance of the
      multi-species biofilms. These results stressed the great interest of extracting
      and culturing pure EA strains from wild EA biofilms to improve the current
      density provided by microbial anodes.

PMID- 22470539
TI  - Pharmacogenetic association of NOS3 variants with cardiovascular disease in
      patients with hypertension: the GenHAT study.
AB  - Nitric oxide synthase 3 (NOS3) catalyzes production of NO in the endothelium and
      may play a role in cardiovascular disease (CVD). We assessed the pharmacogenetic
      associations of three NOS3 polymorphisms and three antihypertensive drugs with
      CVD outcomes. Hypertensive subjects (n = 30,280) from a multi-center, double
      blind clinical trial were randomized to chlorthalidone, amlodipine, or lisinopril
      treatment (mean follow up, 4.9 years). Outcomes included coronary heart disease
      (CHD: fatal CHD and nonfatal myocardial infarction); stroke; heart failure
      (fatal, requiring hospitalization, or outpatient treatment); all-cause mortality;
      and end-stage renal disease (ESRD). Main effects of NOS3 variants on outcome and
      genotype-treatment interactions were tested. For NOS3 -690 C>T (rs3918226), a
      higher hazard ratio (HR) was found in minor allele carriers for CHD (CC = 1.00,
      CT+TT = 1.12 (95% confidence interval (CI) = 1.00-1.26), P = 0.048). For NOS3 
      922 A>G (rs1800779), a higher HR was found in minor allele carriers for heart
      failure (AA = 1.00, AG+GG = 1.10 (CI = 1.00-1.21), P = 0.046). Significant
      pharmacogenetic findings were observed for stroke and all-cause mortality. For 
      690 C>T, a lower HR was observed for stroke in minor allele carriers when treated
      with amlodipine versus lisinopril (CC = 0.85 (CI = 0.73-0.99), CT+TT = 0.49 (CI =
      0.31-0.80), P = 0.04). For glu298asp G>T (rs1799983), a lower HR was observed for
      all-cause mortality in minor allele carriers when treated with amlodipine versus
      lisinopril (GG = 1.01 (CI = 0.91-1.13), GT+TT = 0.85 (CI = 0.75-0.97), P = 0.04).
      We observed significant associations with NOS3 variants and CHD and heart failure
      and significant pharmacogenetic effects for stroke and all cause mortality. This
      suggests that NOS3 variants may potentially provide useful clinical information
      with respect to treatment decisions in the future.

PMID- 22470540
TI  - No evidence for infection of UK prostate cancer patients with XMRV, BK virus,
      Trichomonas vaginalis or human papilloma viruses.
AB  - The prevalence of specific infections in UK prostate cancer patients was
      investigated. Serum from 84 patients and 62 controls was tested for
      neutralisation of xenotropic murine leukaemia virus-related virus (XMRV)
      Envelope. No reactivity was found in the patient samples. In addition, a further
      100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis
      and human papilloma viruses by nucleic acid detection techniques. Despite
      demonstrating DNA integrity and assay sensitivity, we failed to detect the
      presence of any of these agents in DNA samples, bar one sample that was weakly
      positive for HPV16. Therefore we conclude that these infections are absent in
      this typical cohort of men with prostate cancer.

PMID- 22470541
TI  - Methamphetamine causes differential alterations in gene expression and patterns
      of histone acetylation/hypoacetylation in the rat nucleus accumbens.
AB  - Methamphetamine (METH) addiction is associated with several neuropsychiatric
      symptoms. Little is known about the effects of METH on gene expression and
      epigenetic modifications in the rat nucleus accumbens (NAC). Our study
      investigated the effects of a non-toxic METH injection (20 mg/kg) on gene
      expression, histone acetylation, and the expression of the histone
      acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and
      HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after
      the METH injection identified METH-induced changes in the expression of genes
      previously implicated in the acute and longterm effects of psychostimulants,
      including immediate early genes and corticotropin-releasing factor (Crf). In
      contrast, the METH injection caused time-dependent decreases in the expression of
      other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed
      that genes with altered expression participated in behavioral performance, cell
      to-cell signaling, and regulation of gene expression. PCR analyses confirmed the
      changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To
      determine if the METH injection caused post-translational changes in histone
      markers, we used western blot analyses and identified METH-mediated decreases in
      histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub
      fractions. In contrast, the METH injection caused time-dependent increases in
      acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by
      decreased expression of HDAC1 but increased expression of HDAC2 protein levels.
      The histone acetyltransferase, ATF2, showed significant METH-induced increased in
      protein expression. These results suggest that METH-induced alterations in global
      gene expression seen in rat NAC might be related, in part, to METH-induced
      changes in histone acetylation secondary to changes in HAT and HDAC expression.
      The causal role that HATs and HDACs might play in METH-induced gene expression
      needs to be investigated further.

PMID- 22470542
TI  - Role of basal ganglia circuits in resisting interference by distracters: a
      swLORETA study.
AB  - BACKGROUND: The selection of task-relevant information requires both the
      focalization of attention on the task and resistance to interference from
      irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network,
      while focalization additionally involves a ventral frontoparietal network. The
      role of subcortical structures in attention is less clear, despite the fact that
      the striatum interacts significantly with the frontal cortex via frontostriatal
      loops. One means of investigating the basal ganglia's contributions to attention
      is to examine the features of P300 components (i.e. amplitude, latency, and
      generators) in patients with basal ganglia damage (such as in Parkinson's disease
      (PD), in which attention is often impaired). Three-stimulus oddball paradigms can
      be used to study distracter-elicited and target-elicited P300 subcomponents.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to compare distracter- and target
      elicited P300 components, high-density (128-channel) electroencephalograms were
      recorded during a three-stimulus visual oddball paradigm in 15 patients with
      early PD and 15 matched healthy controls. For each subject, the P300 sources were
      localized using standardized weighted low-resolution electromagnetic tomography
      (swLORETA). Comparative analyses (one-sample and two-sample t-tests) were
      performed using SPM5(r) software. The swLORETA analyses showed that PD patients
      displayed fewer dorsolateral prefrontal (DLPF) distracter-P300 generators but no
      significant differences in target-elicited P300 sources; this suggests
      dysfunction of the DLPF cortex when the executive frontostriatal loop is
      disrupted by basal ganglia damage. CONCLUSIONS/SIGNIFICANCE: Our results suggest
      that the cortical attention frontoparietal networks (mainly the dorsal one) are
      modulated by the basal ganglia. Disruption of this network in PD impairs
      resistance to distracters, which results in attention disorders.

PMID- 22470543
TI  - Next-generation phylogeography: a targeted approach for multilocus sequencing of
      non-model organisms.
AB  - The field of phylogeography has long since realized the need and utility of
      incorporating nuclear DNA (nDNA) sequences into analyses. However, the use of
      nDNA sequence data, at the population level, has been hindered by technical
      laboratory difficulty, sequencing costs, and problematic analytical methods
      dealing with genotypic sequence data, especially in non-model organisms. Here, we
      present a method utilizing the 454 GS-FLX Titanium pyrosequencing platform with
      the capacity to simultaneously sequence two species of sea star (Meridiastra
      calcar and Parvulastra exigua) at five different nDNA loci across 16 different
      populations of 20 individuals each per species. We compare results from 3
      populations with traditional Sanger sequencing based methods, and demonstrate
      that this next-generation sequencing platform is more time and cost effective and
      more sensitive to rare variants than Sanger based sequencing. A crucial advantage
      is that the high coverage of clonally amplified sequences simplifies haplotype
      determination, even in highly polymorphic species. This targeted next-generation
      approach can greatly increase the use of nDNA sequence loci in phylogeographic
      and population genetic studies by mitigating many of the time, cost, and
      analytical issues associated with highly polymorphic, diploid sequence markers.

PMID- 22470544
TI  - Local spatial and temporal processes of influenza in Pennsylvania, USA: 2003
      2009.
AB  - BACKGROUND: Influenza is a contagious respiratory disease responsible for annual
      seasonal epidemics in temperate climates. An understanding of how influenza
      spreads geographically and temporally within regions could result in improved
      public health prevention programs. The purpose of this study was to summarize the
      spatial and temporal spread of influenza using data obtained from the
      Pennsylvania Department of Health's influenza surveillance system. METHODOLOGY
      AND FINDINGS: We evaluated the spatial and temporal patterns of laboratory
      confirmed influenza cases in Pennsylvania, United States from six influenza
      seasons (2003-2009). Using a test of spatial autocorrelation, local clusters of
      elevated risk were identified in the South Central region of the state.
      Multivariable logistic regression indicated that lower monthly precipitation
      levels during the influenza season (OR = 0.52, 95% CI: 0.28, 0.94), fewer
      residents over age 64 (OR = 0.27, 95% CI: 0.10, 0.73) and fewer residents with
      more than a high school education (OR = 0.76, 95% CI: 0.61, 0.95) were
      significantly associated with membership in this cluster. In addition, time
      series analysis revealed a temporal lag in the peak timing of the influenza B
      epidemic compared to the influenza A epidemic. CONCLUSIONS: These findings
      illustrate a distinct spatial cluster of cases in the South Central region of
      Pennsylvania. Further examination of the regional transmission dynamics within
      these clusters may be useful in planning public health influenza prevention
      programs.

PMID- 22470545
TI  - Small cationic DDA:TDB liposomes as protein vaccine adjuvants obviate the need
      for TLR agonists in inducing cellular and humoral responses.
AB  - Most subunit vaccines require adjuvants in order to induce protective immune
      responses to the targeted pathogen. However, many of the potent immunogenic
      adjuvants display unacceptable local or systemic reactogenicity. Liposomes are
      spherical vesicles consisting of single (unilamellar) or multiple (multilamellar)
      phospholipid bi-layers. The lipid membranes are interleaved with an aqueous
      buffer, which can be utilised to deliver hydrophilic vaccine components, such as
      protein antigens or ligands for immune receptors. Liposomes, in particular
      cationic DDA:TDB vesicles, have been shown in animal models to induce strong
      humoral responses to the associated antigen without increased reactogenicity, and
      are currently being tested in Phase I human clinical trials. We explored several
      modifications of DDA:TDB liposomes--including size, antigen association and
      addition of TLR agonists--to assess their immunogenic capacity as vaccine
      adjuvants, using Ovalbumin (OVA) protein as a model protein vaccine. Following
      triple homologous immunisation, small unilamellar vesicles (SUVs) with no TLR
      agonists showed a significantly higher capacity for inducing spleen CD8 IFNgamma
      responses against OVA in comparison with the larger multilamellar vesicles
      (MLVs). Antigen-specific antibody reponses were also higher with SUVs. Addition
      of the TLR3 and TLR9 agonists significantly increased the adjuvanting capacity of
      MLVs and OVA-encapsulating dehydration-rehydration vesicles (DRVs), but not of
      SUVs. Our findings lend further support to the use of liposomes as protein
      vaccine adjuvants. Importantly, the ability of DDA:TDB SUVs to induce potent CD8
      T cell responses without the need for adding immunostimulators would avoid the
      potential safety risks associated with the clinical use of TLR agonists in
      vaccines adjuvanted with liposomes.

PMID- 22470546
TI  - Involvement of hypoxia-inducible factor-1 in the inflammatory responses of human
      LAD2 mast cells and basophils.
AB  - We recently showed that hypoxia-inducible factor 1 (HIF-1) plays a crucial role
      in the pro-allergic functions of human basophils by transcriptional control of
      energy metabolism via glycolysis as well as directly triggering expression of the
      angiogenic cytokine vascular endothelium growth factor (VEGF). Here, we
      investigated HIF-1 involvement in controlling the synthesis of angiogenic and
      inflammatory cytokines from various human effector cells stimulated by IgE
      dependent or innate immune triggers. Purified primary human basophils, LAD2 human
      mast cells and THP-1 human myeloid cells were used for investigations of
      FcepsilonRI and Toll-like receptor (TLR) ligand-induced responses. In contrast to
      basophils, LAD2 mast cells expressed background levels of HIF-1alpha, which was
      largely independent of the effects of stem cell factor (SCF). Both mast cells and
      basophils expressed TLR2 and 4, albeit weakly compared to THP-1 cells. Cytokine
      production in mast cells following TLR ligand stimulation was markedly reduced by
      HIF-1alpha knockdown in LAD2 mast cells. In contrast, although HIF-1 is involved
      in IgE-mediated IL-4 secretion from basophils, it is not clearly induced by
      peptidoglycan (PGN). HIF-1alpha accumulation is critical for sustaining human
      allergic effector cell survival and function. This transcription complex
      facilitates generation of both pro-angiogenic and inflammatory cytokines in mast
      cells but has a differential role in basophil stimulation comparing IgE-dependent
      triggering with innate immune stimuli.

PMID- 22470547
TI  - Characterization of apoptosis-related oxidoreductases from Neurospora crassa.
AB  - The genome from Neurospora crassa presented three open reading frames homologous
      to the genes coding for human AIF and AMID proteins, which are flavoproteins with
      oxidoreductase activities implicated in caspase-independent apoptosis. To
      investigate the role of these proteins, namely within the mitochondrial
      respiratory chain, we studied their cellular localization and characterized the
      respective null mutant strains. Efficiency of the respiratory chain was analyzed
      by oxygen consumption studies and supramolecular organization of the OXPHOS
      system was assessed through BN-PAGE analysis in the respective null mutant
      strains. The results demonstrate that, unlike in mammalian systems, disruption of
      AIF in Neurospora does not affect either complex I assembly or function.
      Furthermore, the mitochondrial respiratory chain complexes of the mutant strains
      display a similar supramolecular organization to that observed in the wild type
      strain. Further characterization revealed that N. crassa AIF appears localized to
      both the mitochondria and the cytoplasm, whereas AMID was found exclusively in
      the cytoplasm. AMID2 was detected in both mitochondria and cytoplasm of the amid
      mutant strain, but was barely discernible in wild type extracts, suggesting
      overlapping functions for the two proteins.

PMID- 22470548
TI  - Dissociation of motor task-induced cortical excitability and pain perception
      changes in healthy volunteers.
AB  - BACKGROUND: There is evidence that interventions aiming at modulation of the
      motor cortex activity lead to pain reduction. In order to understand further the
      role of the motor cortex on pain modulation, we aimed to compare the behavioral
      (pressure pain threshold) and neurophysiological effects (transcranial magnetic
      stimulation (TMS) induced cortical excitability) across three different motor
      tasks. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen healthy male subjects were
      enrolled in this randomized, controlled, blinded, cross-over designed study.
      Three different tasks were tested including motor learning with and without
      visual feedback, and simple hand movements. Cortical excitability was assessed
      using single and paired-pulse TMS measures such as resting motor threshold (RMT),
      motor-evoked potential (MEP), intracortical facilitation (ICF), short
      intracortical inhibition (SICI), and cortical silent period (CSP). All tasks
      showed significant reduction in pain perception represented by an increase in
      pressure pain threshold compared to the control condition (untrained hand). ANOVA
      indicated a difference among the three tasks regarding motor cortex excitability
      change. There was a significant increase in motor cortex excitability (as indexed
      by MEP increase and CSP shortening) for the simple hand movements.
      CONCLUSIONS/SIGNIFICANCE: Although different motor tasks involving motor learning
      with and without visual feedback and simple hand movements appear to change pain
      perception similarly, it is likely that the neural mechanisms might not be the
      same as evidenced by differential effects in motor cortex excitability induced by
      these tasks. In addition, TMS-indexed motor excitability measures are not likely
      good markers to index the effects of motor-based tasks on pain perception in
      healthy subjects as other neural networks besides primary motor cortex might be
      involved with pain modulation during motor training.

PMID- 22470549
TI  - Sequence variations of latent membrane protein 2A in Epstein-Barr virus
      associated gastric carcinomas from Guangzhou, southern China.
AB  - Latent membrane protein 2A (LMP2A), expressed in most Epstein-Barr virus (EBV)
      associated malignancies, has been demonstrated to be responsible for the
      maintenance of latent infection and epithelial cell transformation. Besides, it
      could also act as the target for a CTL-based therapy for EBV-associated
      malignancies. In the present study, sequence variations of LMP2A in EBV
      associated gastric carcinoma (EBVaGC) and healthy EBV carriers from Guangzhou,
      southern China, where nasopharyngeal carcinoma (NPC) is endemic, were
      investigated. Widespread sequence variations in the LMP2A gene were found, with
      no sequence identical to the B95.8 prototype. No consistent mutation was detected
      in all isolates. The immunoreceptor tyrosine-based activation motif (ITAM) and PY
      motifs in the amino terminus of LMP2A were strictly conserved, suggesting their
      important roles in virus infection; while 8 of the 17 identified CTL epitopes in
      the transmembrane region of LMP2A were affected by at least one point mutation,
      which may implicate that the effect of LMP2A polymorphisms should be considered
      when LMP2A-targeted immunotherapy is conducted. The polymorphisms of LMP2A in
      EBVaGC in gastric remnant carcinoma (GRC) were for the first time investigated in
      the world. The LMP2A sequence variations in EBVaGC in GRC were somewhat different
      from those in EBVaGC in conventional gastric carcinoma. The sequence variations
      of LMP2A in EBVaGC were similar to those in throat washing of healthy EBV
      carriers, indicating that these variations are due to geographic-associated
      polymorphisms rather than EBVaGC-associated mutations. This, to our best
      knowledge, is the first detailed investigation of LMP2A polymorphisms in EBVaGC
      in Guangzhou, southern China, where NPC is endemic.

PMID- 22470550
TI  - Exploring the caffeine-induced teratogenicity on neurodevelopment using early
      chick embryo.
AB  - Caffeine consumption is worldwide. It has been part of our diet for many
      centuries; indwelled in our foods, drinks, and medicines. It is often perceived
      as a "legal drug", and though it is known to have detrimental effects on our
      health, more specifically, disrupt the normal fetal development following
      excessive maternal intake, much ambiguity still surrounds the precise mechanisms
      and consequences of caffeine-induced toxicity. Here, we employed early chick
      embryos as a developmental model to assess the effects of caffeine on the
      development of the fetal nervous system. We found that administration of caffeine
      led to defective neural tube closures and expression of several abnormal
      morphological phenotypes, which included thickening of the cephalic mesenchymal
      tissues and scattering of somites. Immunocytochemistry of caffeine-treated
      embryos using neural crest cell markers also demonstrated uncharacteristic
      features; HNK1 labeled migratory crest cells exhibited an incontinuous dorsal
      ventral migration trajectory, though Pax7 positive cells of the caffeine-treated
      groups were comparatively similar to the control. Furthermore, the number of
      neurons expressing neurofilament and the degree of neuronal branching were both
      significantly reduced following caffeine administration. The extent of these
      effects was dose-dependent. In conclusion, caffeine exposure can result in
      malformations of the neural tube and induce other teratogenic effects on
      neurodevelopment, although the exact mechanism of these effects requires further
      investigation.

PMID- 22470551
TI  - Framingham risk score and alternatives for prediction of coronary heart disease
      in older adults.
AB  - BACKGROUND: Guidelines for the prevention of coronary heart disease (CHD)
      recommend use of Framingham-based risk scores that were developed in white middle
      aged populations. It remains unclear whether and how CHD risk prediction might be
      improved among older adults. We aimed to compare the prognostic performance of
      the Framingham risk score (FRS), directly and after recalibration, with refit
      functions derived from the present cohort, as well as to assess the utility of
      adding other routinely available risk parameters to FRS. METHODS: Among 2193
      black and white older adults (mean age, 73.5 years) without pre-existing
      cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD
      events, defined as incident myocardial infarction, CHD death, and hospitalization
      for angina or coronary revascularization. RESULTS: During 8-year follow-up, 351
      participants experienced CHD events. The FRS poorly discriminated between persons
      who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and
      underestimated absolute risk prediction by 51% in women and 8% in men.
      Recalibration of the FRS improved absolute risk prediction, particulary for
      women. For both genders, refitting these functions substantially improved
      absolute risk prediction, with similar discrimination to the FRS. Results did not
      differ between whites and blacks. The addition of lifestyle variables, waist
      circumference and creatinine did not improve risk prediction beyond risk factors
      of the FRS. CONCLUSIONS: The FRS underestimates CHD risk in older adults,
      particularly in women, although traditional risk factors remain the best
      predictors of CHD. Re-estimated risk functions using these factors improve
      accurate estimation of absolute risk.

PMID- 22470553
TI  - Unfakeable facial configurations affect strategic choices in trust games with or
      without information about past behavior.
AB  - BACKGROUND: Many human interactions are built on trust, so widespread confidence
      in first impressions generally favors individuals with trustworthy-looking
      appearances. However, few studies have explicitly examined: 1) the contribution
      of unfakeable facial features to trust-based decisions, and 2) how these cues are
      integrated with information about past behavior. METHODOLOGY/PRINCIPAL FINDINGS:
      Using highly controlled stimuli and an improved experimental procedure, we show
      that unfakeable facial features associated with the appearance of trustworthiness
      attract higher investments in trust games. The facial trustworthiness premium is
      large for decisions based solely on faces, with trustworthy identities attracting
      42% more money (Study 1), and remains significant though reduced to 6% when
      reputational information is also available (Study 2). The face trustworthiness
      premium persists with real (rather than virtual) currency and when higher payoffs
      are at stake (Study 3). CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that
      cooperation may be affected not only by controllable appearance cues (e.g.,
      clothing, facial expressions) as shown previously, but also by features that are
      impossible to mimic (e.g., individual facial structure). This unfakeable face
      trustworthiness effect is not limited to the rare situations where people lack
      any information about their partners, but survives in richer environments where
      relevant details about partner past behavior are available.

PMID- 22470552
TI  - Afghanistan's ethnic groups share a Y-chromosomal heritage structured by
      historical events.
AB  - Afghanistan has held a strategic position throughout history. It has been
      inhabited since the Paleolithic and later became a crossroad for expanding
      civilizations and empires. Afghanistan's location, history, and diverse ethnic
      groups present a unique opportunity to explore how nations and ethnic groups
      emerged, and how major cultural evolutions and technological developments in
      human history have influenced modern population structures. In this study we have
      analyzed, for the first time, the four major ethnic groups in present-day
      Afghanistan: Hazara, Pashtun, Tajik, and Uzbek, using 52 binary markers and 19
      short tandem repeats on the non-recombinant segment of the Y-chromosome. A total
      of 204 Afghan samples were investigated along with more than 8,500 samples from
      surrounding populations important to Afghanistan's history through migrations and
      conquests, including Iranians, Greeks, Indians, Middle Easterners, East
      Europeans, and East Asians. Our results suggest that all current Afghans largely
      share a heritage derived from a common unstructured ancestral population that
      could have emerged during the Neolithic revolution and the formation of the first
      farming communities. Our results also indicate that inter-Afghan differentiation
      started during the Bronze Age, probably driven by the formation of the first
      civilizations in the region. Later migrations and invasions into the region have
      been assimilated differentially among the ethnic groups, increasing inter
      population genetic differences, and giving the Afghans a unique genetic diversity
      in Central Asia.

PMID- 22470554
TI  - Contribution of case reports to brain metastases research: systematic review and
      analysis of pattern of citation.
AB  - Research activity related to different aspects of prevention, prediction,
      diagnosis and treatment of brain metastases has increased during recent years.
      One of the major databases (Scopus) contains 942 scientific articles that were
      published during the 5-year time period 2006-2010. Of these, 195 (21%) reported
      on single patient cases and 12 (1%) were reports of 2 cases. Little is known
      about their influence on advancement of the field or scientific merits. Do brain
      metastases case reports attract attention and provide stimuli for further
      research or do they go largely unrecognized? Different measures of impact,
      visibility and quality of published research are available, each with its own
      pros and cons. For the present evaluation, article citation rate was chosen. The
      median number of citations overall and stratified by year of publication was 0,
      except for the year 2006 when it was 2. As compared to other articles, case
      reports remained more often without citation (p<0.05 except for 2006 data). All
      case reports with 10 or more citations (n = 6) reported on newly introduced
      anticancer drugs, which commonly are prescribed to treat extracranial metastases,
      and the responses observed in single patients with brain metastases. Average
      annual numbers of citations were also calculated. The articles with most
      citations per year were the same six case reports mentioned above (the only ones
      that obtained more than 2.0 citations per year). Citations appeared to gradually
      increase during the first two years after publication but remained on a generally
      low or modest level. It cannot be excluded that case reports without citation
      provide interesting information to some clinicians or researchers. Apparently,
      case reports describing unexpected therapeutic success gain more attention, at
      least in terms of citation, than others.

PMID- 22470555
TI  - Validation of a Dutch risk score predicting poor outcome in adults with bacterial
      meningitis in Vietnam and Malawi.
AB  - We have previously developed and validated a prognostic model to predict the risk
      for unfavorable outcome in Dutch adults with bacterial meningitis. The aim of the
      current study was to validate this model in adults with bacterial meningitis from
      two developing countries, Vietnam and Malawi. Demographic and clinical
      characteristics of Vietnamese (n = 426), Malawian patients (n = 465) differed
      substantially from those of Dutch patients (n = 696). The Dutch model
      underestimated the risk of poor outcome in both Malawi and Vietnam. The
      discrimination of the original model (c-statistic [c] 0.84; 95% confidence
      interval 0.81 to 0.86) fell considerably when re-estimated in the Vietnam cohort
      (c = 0.70) or in the Malawian cohort (c = 0.68). Our validation study shows that
      new prognostic models have to be developed for these countries in a sufficiently
      large series of unselected patients.

PMID- 22470556
TI  - Acute pain and a motivational pathway in adult rats: influence of early life pain
      experience.
AB  - BACKGROUND: The importance of neonatal experience upon behaviour in later life is
      increasingly recognised. The overlap between pain and reward pathways led us to
      hypothesise that neonatal pain experience influences reward-related pathways and
      behaviours in adulthood. METHODOLOGY/PRINCIPAL FINDINGS: Rat pups received repeat
      plantar skin incisions (neonatal IN) or control procedures (neonatal anesthesia
      only, AN) at postnatal days (P)3, 10 and 17. When adult, rats with neonatal 'pain
      history' showed greater sensory sensitivity than control rats following acute
      plantar skin incision. Motivational behaviour in the two groups of rats was
      tested in a novelty-induced hypophagia (NIH) paradigm. The sensitivity of this
      paradigm to pain-induced changes in motivational behaviour was shown by
      significant increases in the time spent in the central zone of the arena (43.7+/
      5.9% vs. 22.5+/-6.7%, p<0.05), close to centrally placed food treats, and
      decreased number of rears (9.5+/-1.4 vs. 19.2+/-2.3, p<0.001) in rats with acute
      plantar skin incision compared to naive, uninjured animals. Rats with a neonatal
      'pain history' showed the same pain-induced behaviour in the novelty-induced
      hypophagia paradigm as controls. However, differences were observed in reward
      related neural activity between the two groups. Two hours after behavioural
      testing, brains were harvested and neuronal activity mapped using c-Fos
      expression in lateral hypothalamic orexin neurons, part of a specific reward
      seeking pathway. Pain-induced activity in orexin neurons of control rats (18.4+/
      2.8%) was the same as in uninjured naive animals (15.5+/-2.6%), but in those rats
      with a 'pain history', orexinergic activity was significantly increased (27.2+/
      4.1%, p<0.01). Furthermore the extent of orexin neuron activation in individual
      rats with a 'pain history' was highly correlated with their motivational
      behaviour (r = -0.86, p = 0.01). CONCLUSIONS/SIGNIFICANCE: These results show
      that acute pain alters motivational behaviour and that neonatal pain experience
      causes long-term changes in brain motivational orexinergic pathways, known to
      modulate mesolimbic dopaminergic reward circuitry.

PMID- 22470557
TI  - Overexpression of DNA polymerase zeta reduces the mitochondrial mutability caused
      by pathological mutations in DNA polymerase gamma in yeast.
AB  - In yeast, DNA polymerase zeta (Rev3 and Rev7) and Rev1, involved in the error
      prone translesion synthesis during replication of nuclear DNA, localize also in
      mitochondria. We show that overexpression of Rev3 reduced the mtDNA extended
      mutability caused by a subclass of pathological mutations in Mip1, the yeast
      mitochondrial DNA polymerase orthologous to human Pol gamma. This beneficial
      effect was synergistic with the effect achieved by increasing the dNTPs pools.
      Since overexpression of Rev3 is detrimental for nuclear DNA mutability, we
      constructed a mutant Rev3 isoform unable to migrate into the nucleus: its
      overexpression reduced mtDNA mutability without increasing the nuclear one.

PMID- 22470558
TI  - In search of the optimal surgical treatment for velopharyngeal dysfunction in
      22q11.2 deletion syndrome: a systematic review.
AB  - BACKGROUND: Patients with the 22q11.2 deletion syndrome (22qDS) and
      velopharyngeal dysfunction (VPD) tend to have residual VPD following surgery.
      This systematic review seeks to determine whether a particular surgical procedure
      results in superior speech outcome or less morbidity. METHODOLOGY/ PRINCIPAL
      FINDINGS: A combined computerized and hand-search yielded 70 studies, of which 27
      were deemed relevant for this review, reporting on a total of 525 patients with
      22qDS and VPD undergoing surgery for VPD. All studies were levels 2c or 4
      evidence. The methodological quality of these studies was assessed using criteria
      based on the Cochrane Collaboration's tool for assessing risk of bias.
      Heterogeneous groups of patients were reported on in the studies. The surgical
      procedure was often tailored to findings on preoperative imaging. Overall, 50% of
      patients attained normal resonance, 48% attained normal nasal emissions scores,
      and 83% had understandable speech postoperatively. However, 5% became hyponasal,
      1% had obstructive sleep apnea (OSA), and 17% required further surgery. There
      were no significant differences in speech outcome between patients who underwent
      a fat injection, Furlow or intravelar veloplasty, pharyngeal flap pharyngoplasty,
      Honig pharyngoplasty, or sphincter pharyngoplasty or Hynes procedures. There was
      a trend that a lower percentage of patients attained normal resonance after a fat
      injection or palatoplasty than after the more obstructive pharyngoplasties (11
      18% versus 44-62%, p = 0.08). Only patients who underwent pharyngeal flaps or
      sphincter pharyngoplasties incurred OSA, yet this was not statistically
      significantly more often than after other procedures (p = 0.25). More patients
      who underwent a palatoplasty needed further surgery than those who underwent a
      pharyngoplasty (50% versus 7-13%, p = 0.03). CONCLUSIONS/ SIGNIFICANCE: In the
      heterogeneous group of patients with 22qDS and VPD, a grade C recommendation can
      be made to minimize the morbidity of further surgery by choosing to perform a
      pharyngoplasty directly instead of only a palatoplasty.

PMID- 22470559
TI  - Epigenetic silencing of the circadian clock gene CRY1 is associated with an
      indolent clinical course in chronic lymphocytic leukemia.
AB  - Disruption of circadian rhythm is believed to play a critical role in cancer
      development. Cryptochrome 1 (CRY1) is a core component of the mammalian circadian
      clock and we have previously shown its deregulated expression in a subgroup of
      patients with chronic lymphocytic leukemia (CLL). Using real-time RT-PCR in a
      cohort of 76 CLL patients and 35 normal blood donors we now demonstrate that
      differential CRY1 mRNA expression in high-risk (HR) CD38+/immunoglobulin variable
      heavy chain gene (IgVH) unmutated patients as compared to low-risk (LR) CD38
      /IgVH mutated patients can be attributed to down-modulation of CRY1 in LR CLL
      cases. Analysis of the DNA methylation profile of the CRY1 promoter in a subgroup
      of 57 patients revealed that CRY1 expression in LR CLL cells is silenced by
      aberrant promoter CpG island hypermethylation. The methylation pattern of the
      CRY1 promoter proved to have high prognostic impact in CLL where aberrant
      promoter methylation predicted a favourable outcome. CRY1 mRNA transcript levels
      did not change over time in the majority of patients where sequential samples
      were available for analysis. We also compared the CRY1 expression in CLL with
      other lymphoid malignancies and observed epigenetic silencing of CRY1 in a
      patient with B cell acute lymphoblastic leukemia (B-ALL).

PMID- 22470560
TI  - The group delay and suppression pattern of the cochlear microphonic potential
      recorded at the round window.
AB  - BACKGROUND: It is commonly assumed that the cochlear microphonic potential (CM)
      recorded from the round window (RW) is generated at the cochlear base. Based on
      this assumption, the low-frequency RW CM has been measured for evaluating the
      integrity of mechanoelectrical transduction of outer hair cells at the cochlear
      base and for studying sound propagation inside the cochlea. However, the group
      delay and the origin of the low-frequency RW CM have not been demonstrated
      experimentally. METHODOLOGY/PRINCIPAL FINDINGS: This study quantified the intra
      cochlear group delay of the RW CM by measuring RW CM and vibrations at the stapes
      and basilar membrane in gerbils. At low sound levels, the RW CM showed a
      significant group delay and a nonlinear growth at frequencies below 2 kHz.
      However, at high sound levels or at frequencies above 2 kHz, the RW CM magnitude
      increased proportionally with sound pressure, and the CM phase in respect to the
      stapes showed no significant group delay. After the local application of
      tetrodotoxin the RW CM below 2 kHz became linear and showed a negligible group
      delay. In contrast to RW CM phase, the BM vibration measured at location ~2.5 mm
      from the base showed high sensitivity, sharp tuning, and nonlinearity with a
      frequency-dependent group delay. At low or intermediate sound levels, low
      frequency RW CMs were suppressed by an additional tone near the probe-tone
      frequency while, at high sound levels, they were partially suppressed only at
      high frequencies. CONCLUSIONS/SIGNIFICANCE: We conclude that the group delay of
      the RW CM provides no temporal information on the wave propagation inside the
      cochlea, and that significant group delay of low-frequency CMs results from the
      auditory nerve neurophonic potential. Suppression data demonstrate that the
      generation site of the low-frequency RW CM shifts from apex to base as the probe
      tone level increases.

PMID- 22470561
TI  - Risk factors for severe cases of 2009 influenza A (H1N1): a case control study in
      Zhejiang Province, China.
AB  - Few case control studies were conducted to explore risk factors for severe cases
      of 2009 influenza A (H1N1) with the mild cases as controls. Mild and severe cases
      of 2009 influenza A (H1N1), 230 cases each, were randomly selected from nine
      cities in Zhejiang Province, China, and unmatched case control study was
      conducted. This study found that it averagely took 5 days for the severe cases of
      2009 influenza A (H1N1) to start antiviral therapy away from onset, 2 days later
      than mild cases. Having chronic underlying diseases and bad psychological health
      combined with chronic underlying diseases were two important risk factors for
      severe cases, and their OR values were 2.39 and 5.85 respectively. Timely anti
      viral therapy was a protective factor for severe cases (OR = 0.35, 95% CI: [0.18
      0.67]). In conclusion, psychological health education and intervention, as well
      as timely anti-viral therapy, could not be ignored in the prevention, control and
      treatment of 2009 influenza A (H1N1).

PMID- 22470562
TI  - Oxidative stress in HPV-driven viral carcinogenesis: redox proteomics analysis of
      HPV-16 dysplastic and neoplastic tissues.
AB  - Genital infection by high risk Human Papillomavirus (HR-HPV), although recognized
      as the main etio-pathogenetic factor of cervical cancer, is not per se sufficient
      to induce tumour development. Oxidative stress (OS) represents an interesting and
      under-explored candidate as a promoting factor in HPV-initiated carcinogenesis.
      To gain insight into the role of OS in cervical cancer, HPV-16 positive tissues
      were collected from patients with invasive squamous cervical carcinoma, from
      patients with High Grade dysplastic HPV lesions and from patients with no
      clinical evidence of HPV lesions. After virological characterization, modulation
      of proteins involved in the redox status regulation was investigated. ERp57 and
      GST were sharply elevated in dysplastic and neoplastic tissues. TrxR2 peaked in
      dysplastic samples while iNOS was progressively reduced in dysplastic and
      neoplastic samples. By redox proteomic approach, five proteins were found to have
      increased levels of carbonyls in dysplastic samples respect to controls namely:
      cytokeratin 6, actin, cornulin, retinal dehydrogenase and GAPDH. In carcinoma
      samples the peptidyl-prolyl cis-trans isomerase A, ERp57, serpin B3, Annexin 2
      and GAPDH were found less oxidized than in dysplastic tissues. HPV16 neoplastic
      progression seems associated with increased oxidant environment. In dysplastic
      tissues the oxidative modification of DNA and proteins involved in cell
      morphogenesis and terminal differentiation may provide the conditions for the
      neoplastic progression. Conversely cancer tissues seem to attain an improved
      control on oxidative damage as shown by the selective reduction of carbonyl
      adducts on key detoxifying/pro-survival proteins.

PMID- 22470563
TI  - Asymmetric cortical adaptation effects during alternating auditory stimulation.
AB  - The present study investigates hemispheric asymmetries in the neural adaptation
      processes occurring during alternating auditory stimulation. Stimuli were two
      monaural pure tones having a frequency of 400 or 800 Hz and a duration of 500 ms.
      Electroencephalogram (EEG) was recorded from 14 volunteers during the
      presentation of the following stimulus sequences, lasting 12 s each: 1) evoked
      potentials (EP condition, control), 2) alternation of frequency and ear (FE
      condition), 3) alternation of frequency (F condition), and 4) alternation of ear
      (E condition). Main results showed that in the central area of the left
      hemisphere (around C3 site) the N100 response underwent adaptation in all
      patterns of alternation, whereas in the same area of the right hemisphere the
      tones presented at the right ear in the FE produced no adaptation. Moreover, the
      responses to right-ear stimuli showed a difference between hemispheres in the E
      condition, which produced less adaptation in the left hemisphere. These effects
      are discussed in terms of lateral symmetry as a product of hemispheric, pathway
      and ear asymmetries.

PMID- 22470564
TI  - The tandem CARDs of NOD2: intramolecular interactions and recognition of RIP2.
AB  - Caspase recruitment domains (CARDs) are homotypic protein interaction modules
      that link the stimulus-dependent assembly of large signaling platforms such as
      inflammasomes to the activation of downstream effectors that often include
      caspases and kinases and thereby play an important role in the regulation of
      inflammatory and apoptotic signaling pathways. NOD2 belongs to the NOD-like (NLR)
      family of intracellular pattern recognition receptors (PRR) and induces
      activation of the NF-kappaB pathway in response to the recognition of bacterial
      components. This process requires the specific recognition of the CARD of the
      protein kinase RIP2 by the tandem CARDs of NOD2. Here we demonstrate that the
      tandem CARDs of NOD2 are engaged in an intramolecular interaction that is
      important for the structural stability of this region. Using a combination of ITC
      and pull-down experiments we identify distinct surface areas that are involved in
      the intramolecular tandem CARD interaction and the interaction with the
      downstream effector RIP2. Our findings indicate that while CARDa of NOD2 might be
      the primary binding partner of RIP2 the two CARDs of NOD2 do not act
      independently of one another but may cooperate to from a binding surface that is
      distinct from that of single CARDs.

PMID- 22470565
TI  - Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation
      and lysosomal cholesterol storage in Kupffer cells.
AB  - BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by
      steatosis and inflammation, which can further progress into fibrosis and
      cirrhosis. Recently, we demonstrated that combined deletion of the two main
      scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1), which are
      important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The
      individual contributions of these receptors to NASH and the intracellular
      mechanisms by which they contribute to inflammation have not been established. We
      hypothesize that CD36 and MSR1 contribute independently to the onset of
      inflammation in NASH, by affecting intracellular cholesterol distribution inside
      Kupffer cells (KCs). METHODS & RESULTS: Ldlr(-/-) mice were transplanted with
      wild-type (Wt), Cd36(-/-) or Msr1(-/-) bone marrow and fed a Western diet for 3
      months. Cd36(-/-)- and Msr1(-/-)- transplanted (tp) mice showed a similar
      reduction in hepatic inflammation compared to Wt-tp mice. While the total amount
      of cholesterol inside KCs was similar in all groups, KCs of Cd36(-/-)- and Msr1(
      /-)-tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp
      mice showed increased lysosomal cholesterol accumulation. CONCLUSION: CD36 and
      MSR1 contribute similarly and independently to the progression of inflammation in
      NASH. One possible explanation for the inflammatory response related to
      expression of these receptors could be abnormal cholesterol trafficking in KCs.
      These data provide a new basis for prevention and treatment of NASH.

PMID- 22470566
TI  - The early postnatal nonhuman primate neocortex contains self-renewing multipotent
      neural progenitor cells.
AB  - The postnatal neocortex has traditionally been considered a non-neurogenic
      region, under non-pathological conditions. A few studies suggest, however, that a
      small subpopulation of neural cells born during postnatal life can differentiate
      into neurons that take up residence within the neocortex, implying that postnatal
      neurogenesis could occur in this region, albeit at a low level. Evidence to
      support this hypothesis remains controversial while the source of putative neural
      progenitors responsible for generating new neurons in the postnatal neocortex is
      unknown. Here we report the identification of self-renewing multipotent neural
      progenitor cells (NPCs) derived from the postnatal day 14 (PD14) marmoset monkey
      primary visual cortex (V1, striate cortex). While neuronal maturation within V1
      is well advanced by PD14, we observed cells throughout this region that co
      expressed Sox2 and Ki67, defining a population of resident proliferating
      progenitor cells. When cultured at low density in the presence of epidermal
      growth factor (EGF) and/or fibroblast growth factor 2 (FGF-2), dissociated V1
      tissue gave rise to multipotent neurospheres that exhibited the ability to
      differentiate into neurons, oligodendrocytes and astrocytes. While the capacity
      to generate neurones and oligodendrocytes was not observed beyond the third
      passage, astrocyte-restricted neurospheres could be maintained for up to 6
      passages. This study provides the first direct evidence for the existence of
      multipotent NPCs within the postnatal neocortex of the nonhuman primate. The
      potential contribution of neocortical NPCs to neural repair following injury
      raises exciting new possibilities for the field of regenerative medicine.

PMID- 22470567
TI  - Discovery of novel microRNAs in rat kidney using next generation sequencing and
      microarray validation.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of
      biological processes. The latest version of the miRBase database (Release 18)
      includes 1,157 mouse and 680 rat mature miRNAs. Only one new rat mature miRNA was
      added to the rat miRNA database from version 16 to version 18 of miRBase,
      suggesting that many rat miRNAs remain to be discovered. Given the importance of
      rat as a model organism, discovery of the completed set of rat miRNAs is
      necessary for understanding rat miRNA regulation. In this study, next generation
      sequencing (NGS), microarray analysis and bioinformatics technologies were
      applied to discover novel miRNAs in rat kidneys. MiRanalyzer was utilized to
      analyze the sequences of the small RNAs generated from NGS analysis of rat kidney
      samples. Hundreds of novel miRNA candidates were examined according to the
      mappings of their reads to the rat genome, presence of sequences that can form a
      miRNA hairpin structure around the mapped locations, Dicer cleavage patterns, and
      the levels of their expression determined by both NGS and microarray analyses.
      Nine novel rat hairpin precursor miRNAs (pre-miRNA) were discovered with high
      confidence. Five of the novel pre-miRNAs are also reported in other species while
      four of them are rat specific. In summary, 9 novel pre-miRNAs (14 novel mature
      miRNAs) were identified via combination of NGS, microarray and bioinformatics
      high-throughput technologies.

PMID- 22470568
TI  - Extract of Pleurotus pulmonarius suppresses liver cancer development and
      progression through inhibition of VEGF-induced PI3K/AKT signaling pathway.
AB  - Liver cancer or hepatocellular carcinoma is one of the leading causes of cancer
      related deaths. Conventional chemotherapies are limited by the development of
      drug resistance and various side effects. Because of its non-toxicity and potent
      biopharmacological activity, metabolites derived from mushrooms have received
      more attention in cancer therapy. Our previous studies have demonstrated the
      anticancer effects of polysaccharide-protein complexes derived from the Pleurotus
      mushrooms. The aim of this study was to investigate the underlying molecular
      mechanism of the anticancer activity of a hot water extract containing a
      polysaccharide-protein complex isolated from Pleurotus pulmonarius (PP) in liver
      cancer cells. Our results indicated that exposure of liver cancer cells to PP not
      only significantly reduced the in vitro cancer cell proliferation and invasion
      but also enhanced the drug-sensitivity to the chemotherapeutic drug Cisplatin.
      Both oral administration and intraperitoneal injection of PP significantly
      inhibited the tumor growth in xenograft BALB/c nude mice. PP triggered a marked
      suppression of the PI3K/AKT signaling pathway in liver cancer cells in vitro and
      in vivo, and overexpression of the constitutively active form of AKT, Myr-AKT,
      abrogated this effect and the inhibited proliferation and invasion by PP. Both
      western blot and ELISA results showed that PP-treated liver cancer cells had
      reduced expression and secretion of vascular endothelial growth factor (VEGF).
      Addition of recombinant human VEGF attenuated the inhibitory effects of PP on
      PI3K/AKT pathway and the cancer phenotypes. Our results demonstrated that PP
      suppressed the proliferation, invasion, and drug-resistance of liver cancer cells
      in vitro and in vivo, mediated by the inhibition of autocrine VEGF-induced
      PI3K/AKT signaling pathway. This study suggests the potential therapeutic
      implication of PP in the treatment of human liver cancer.

PMID- 22470569
TI  - Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis
      and cytokine production in mice.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is a post-infectious
      polyradiculoneuropathy, frequently associated with antecedent Campylobacter
      jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo
      oligosaccharide (LOS) is considered a risk factor for development of GBS as it
      crucially determines the structural homology between LOS and gangliosides,
      explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C.
      jejuni are recognised by TLR4 and sialoadhesin; however, the functional
      implications of these interactions in vivo are unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study we investigated the effects of bacterial sialylation on
      phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo.
      Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains
      and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show
      that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MPhi,
      but not by BM-DC. In addition, LOS sialylation increased the production of IL-10,
      IL-6 and IFN-beta by both BM-MPhi and BM-DC. Subsequent in vivo experiments
      revealed that sialylation augmented the deposition of fluorescent bacteria in
      splenic DC, but not macrophages. In addition, sialylation significantly amplified
      the production of type I interferons, which was independent of pDC.
      CONCLUSIONS/SIGNIFICANCE: These results identify novel immune stimulatory effects
      of C. jejuni sialylation, which may be important in inducing cross-reactive
      humoral responses that cause GBS.

PMID- 22470570
TI  - Flexible programming of cell-free protein synthesis using magnetic bead
      immobilized plasmids.
AB  - The use of magnetic bead-immobilized DNA as movable template for cell-free
      protein synthesis has been investigated. Magnetic microbeads containing
      chemically conjugated plasmids were used to direct cell-free protein synthesis,
      so that protein generation could be readily programmed, reset and reprogrammed.
      Protein synthesis by using this approach could be ON/OFF-controlled through
      repeated addition and removal of the microbead-conjugated DNA and employed in
      sequential expression of different genes in a same reaction mixture. Since the
      incubation periods of individual template plasmids are freely controllable,
      relative expression levels of multiple proteins can be tuned to desired levels.
      We expect that the presented results will find wide application to the flexible
      design and execution of synthetic pathways in cell-free chassis.

PMID- 22470571
TI  - Visual acuity measures do not reliably detect childhood refractive error--an
      epidemiological study.
AB  - PURPOSE: To investigate the utility of uncorrected visual acuity measures in
      screening for refractive error in white school children aged 6-7-years and 12-13
      years. METHODS: The Northern Ireland Childhood Errors of Refraction (NICER) study
      used a stratified random cluster design to recruit children from schools in
      Northern Ireland. Detailed eye examinations included assessment of logMAR visual
      acuity and cycloplegic autorefraction. Spherical equivalent refractive data from
      the right eye were used to classify significant refractive error as myopia of at
      least 1DS, hyperopia as greater than +3.50DS and astigmatism as greater than
      1.50DC, whether it occurred in isolation or in association with myopia or
      hyperopia. RESULTS: Results are presented from 661 white 12-13-year-old and 392
      white 6-7-year-old school-children. Using a cut-off of uncorrected visual acuity
      poorer than 0.20 logMAR to detect significant refractive error gave a sensitivity
      of 50% and specificity of 92% in 6-7-year-olds and 73% and 93% respectively in 12
      13-year-olds. In 12-13-year-old children a cut-off of poorer than 0.20 logMAR had
      a sensitivity of 92% and a specificity of 91% in detecting myopia and a
      sensitivity of 41% and a specificity of 84% in detecting hyperopia. CONCLUSIONS:
      Vision screening using logMAR acuity can reliably detect myopia, but not
      hyperopia or astigmatism in school-age children. Providers of vision screening
      programs should be cognisant that where detection of uncorrected hyperopic and/or
      astigmatic refractive error is an aspiration, current UK protocols will not
      effectively deliver.

PMID- 22470572
TI  - Multilocus sequence typing of genital Chlamydia trachomatis in Norway reveals
      multiple new sequence types and a large genetic diversity.
AB  - BACKGROUND: The Chlamydia trachomatis incidence rate in Finnmark, the most
      northern and sparsely populated county in Norway, has been twice the national
      average. This population based cross-sectional study among Finnmark high school
      students had the following aims: i) to examine distribution of multilocus
      sequence types (STs) of C. trachomatis in a previously unmapped area, ii) to
      compare chlamydia genetic diversity in Finnmark with that of two urban regions,
      and iii) to compare discriminatory capacity of multilocus sequence typing (MLST)
      with conventional ompA sequencing in a large number of chlamydia specimens.
      METHODOLOGY: ompA sequencing and a high-resolution MLST system based on PCR
      amplification and DNA sequencing of five highly variable genetic regions were
      used. Eighty chlamydia specimens from adolescents aged 15-20 years in Finnmark
      were collected in five high schools (n = 60) and from routine clinical samples in
      the laboratory (n = 20). These were compared to routine clinical samples from
      adolescents in Tromso (n = 80) and Trondheim (n = 88), capitals of North and
      Central Norway, respectively. PRINCIPAL FINDINGS: ompA sequencing detected 11
      genotypes in 248 specimens from all three areas. MLST displayed 50 STs providing
      a five-fold higher resolution. Two-thirds of all STs were novel. The common ompA
      E/Bour genotype comprised 46% and resolved into 24 different STs. MLST identified
      the Swedish new variant of C. trachomatis not discriminated by ompA sequencing.
      Simpson's discriminatory index (D) was 0.93 for MLST, while a corrected D(c) was
      0.97. There were no statistically significant differences in ST genetic diversity
      between geographic areas. Finnmark had an atypical genovar distribution with G
      being predominant. This was mainly due to expansion of specific STs of which the
      novel ST161 was unique for Finnmark. CONCLUSIONS/SIGNIFICANCE: MLST revealed
      multiple new STs and a larger genetic diversity in comparison to ompA sequencing
      and proved to be a useful tool in molecular epidemiology of chlamydia infections.

PMID- 22470573
TI  - Genome sequence and transcriptome analysis of the radioresistant bacterium
      Deinococcus gobiensis: insights into the extreme environmental adaptations.
AB  - The desert is an excellent model for studying evolution under extreme
      environments. We present here the complete genome and ultraviolet (UV) radiation
      induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the
      cold Gobi desert and shows higher tolerance to gamma radiation and UV light than
      all other known microorganisms. Nearly half of the genes in the genome encode
      proteins of unknown function, suggesting that the extreme resistance phenotype
      may be attributed to unknown genes and pathways. D. gobiensis also contains a
      surprisingly large number of horizontally acquired genes and predicted mobile
      elements of different classes, which is indicative of adaptation to extreme
      environments through genomic plasticity. High-resolution RNA-Seq transcriptome
      analyses indicated that 30 regulatory proteins, including several well-known
      regulators and uncharacterized protein kinases, and 13 noncoding RNAs were
      induced immediately after UV irradiation. Particularly interesting is the UV
      irradiation induction of the phrB and recB genes involved in photoreactivation
      and recombinational repair, respectively. These proteins likely include key
      players in the immediate global transcriptional response to UV irradiation. Our
      results help to explain the exceptional ability of D. gobiensis to withstand
      environmental extremes of the Gobi desert, and highlight the metabolic features
      of this organism that have biotechnological potential.

PMID- 22470574
TI  - Dissociable components of cognitive control: an event-related potential (ERP)
      study of response inhibition and interference suppression.
AB  - BACKGROUND: Cognitive control refers to the ability to selectively attend and
      respond to task-relevant events while resisting interference from distracting
      stimuli or prepotent automatic responses. The current study aimed to determine
      whether interference suppression and response inhibition are separable component
      processes of cognitive control. METHODOLOGY/PRINCIPAL FINDINGS: Fourteen young
      adults completed a hybrid Go/Nogo flanker task and continuous EEG data were
      recorded concurrently. The incongruous flanker condition (that required
      interference suppression) elicited a more centrally distributed topography with a
      later N2 peak than the Nogo condition (that required response inhibition).
      CONCLUSIONS/SIGNIFICANCE: These results provide evidence for the dissociability
      of interference suppression and response inhibition, indicating that taxonomy of
      inhibition is warranted with the integration of research evidence from
      neuroscience.

PMID- 22470575
TI  - When subterranean termites challenge the rules of fungal epizootics.
AB  - Over the past 50 years, repeated attempts have been made to develop biological
      control technologies for use against economically important species of
      subterranean termites, focusing primarily on the use of the entomopathogenic
      fungus Metarhizium anisopliae. However, no successful field implementation of
      biological control has been reported. Most previous work has been conducted under
      the assumption that environmental conditions within termite nests would favor the
      growth and dispersion of entomopathogenic agents, resulting in an epizootic.
      Epizootics rely on the ability of the pathogenic microorganism to self-replicate
      and disperse among the host population. However, our study shows that due to
      multilevel disease resistance mechanisms, the incidence of an epizootic within a
      group of termites is unlikely. By exposing groups of 50 termites in planar arenas
      containing sand particles treated with a range of densities of an
      entomopathogenic fungus, we were able to quantify behavioral patterns as a
      function of the death ratios resulting from the fungal exposure. The inability of
      the fungal pathogen M. anisopliae to complete its life cycle within a Coptotermes
      formosanus (Isoptera: Rhinotermitidae) group was mainly the result of cannibalism
      and the burial behavior of the nest mates, even when termite mortality reached up
      to 75%. Because a subterranean termite colony, as a superorganism, can prevent
      epizootics of M. anisopliae, the traditional concepts of epizootiology may not
      apply to this social insect when exposed to fungal pathogens, or other pathogen
      for which termites have evolved behavioral and physiological means of disrupting
      their life cycle.

PMID- 22470576
TI  - Insect neuropeptide bursicon homodimers induce innate immune and stress genes
      during molting by activating the NF-kappaB transcription factor Relish.
AB  - BACKGROUND: Bursicon is a heterodimer neuropeptide composed of two cystine knot
      proteins, bursicon alpha (burs alpha) and bursicon beta (burs beta), that elicits
      cuticle tanning (melanization and sclerotization) through the Drosophila leucine
      rich repeats-containing G protein-coupled receptor 2 (DLGR2). Recent studies show
      that both bursicon subunits also form homodimers. However, biological functions
      of the homodimers have remained unknown until now. METHODOLOGY/PRINCIPAL
      FINDINGS: In this report, we show in Drosophila melanogaster that both bursicon
      homodimers induced expression of genes encoding antimicrobial peptides (AMPs) in
      neck-ligated adults following recombinant homodimer injection and in larvae fat
      body after incubation with recombinant homodimers. These AMP genes were also up
      regulated in 24 h old unligated flies (when the endogenous bursicon level is low)
      after injection of recombinant homodimers. Up-regulation of AMP genes by the
      homodimers was accompanied by reduced bacterial populations in fly assay
      preparations. The induction of AMP expression is via activation of the NF-kappaB
      transcription factor Relish in the immune deficiency (Imd) pathway. The influence
      of bursicon homodimers on immune function does not appear to act through the
      heterodimer receptor DLGR2, i.e. novel receptors exist for the homodimers.
      CONCLUSIONS/SIGNIFICANCE: Our results reveal a mechanism of CNS-regulated
      prophylactic innate immunity during molting via induced expression of genes
      encoding AMPs and genes of the Turandot family. Turandot genes are also up
      regulated by a broader range of extreme insults. From these data we infer that
      CNS-generated bursicon homodimers mediate innate prophylactic immunity to both
      stress and infection during the vulnerable molting cycle.

PMID- 22470577
TI  - Bacterial diversity stabilizes community productivity.
AB  - BACKGROUND: Stability is a crucial ecosystem feature gaining particular
      importance in face of increasing anthropogenic stressors. Biodiversity is
      considered to be a driving biotic force maintaining stability, and in this study
      we investigate how different indices of biodiversity affect the stability of
      communities in varied abiotic (composition of available resources) and biotic
      (invasion) contexts. METHODOLOGY/PRINCIPAL FINDINGS: We set up microbial
      microcosms to study the effects of genotypic diversity on the reliability of
      community productivity, defined as the inverse of the coefficient of variation of
      across-treatment productivity, in different environmental contexts. We
      established a bacterial diversity gradient ranging from 1 to 8 Pseudomonas
      fluorescens genotypes and grew the communities in different resource environments
      or in the presence of model invasive species. Biodiversity significantly
      stabilized community productivity across treatments in both experiments. Path
      analyses revealed that different aspects of diversity determined stability:
      genotypic richness stabilized community productivity across resource
      environments, whereas functional diversity determined stability when subjected to
      invasion. CONCLUSIONS/SIGNIFICANCE: Biodiversity increases the stability of
      microbial communities against both biotic and abiotic environmental
      perturbations. Depending on stressor type, varying aspects of biodiversity
      contribute to the stability of ecosystem functions. The results suggest that both
      genetic and functional diversity need to be preserved to ensure buffering of
      communities against abiotic and biotic stresses.

PMID- 22470579
TI  - Journal of radiology case reports - policies.
AB  - This article describes aim and policies for authors and readers of the
      interactive Journal of Radiology Case Reports.

PMID- 22470578
TI  - A new interactive Radiology journal.
AB  - This first issue of the Journal of Radiology Case Reports is dedicated to the
      concept of this new kind of interactive Radiology journals.

PMID- 22470580
TI  - A new generation of journals is born.
AB  - The 21(st) century has provided new technical and educational opportunities as
      well as challenges which have not been approached and exploited sufficiently by
      traditional scientific journals. Furthermore, case reports are usually
      "neglected" by traditional journals for a variety of reasons, including limited
      space in the hardcopy version of the journal issue and priority over original
      research and review articles. The Journal of Radiology Case Reports is a new
      generation of journals, which is dedicated to provide open-access, high-quality,
      peer-reviewed and interactive Radiology case reports.

PMID- 22470581
TI  - An unusual manifestation of acute appendicitis with left flank pain.
AB  - The author presents a case with an unusual presentation of early appendicitis.
      The patient presented initially with left sided flank pain. Workup for
      nephrolithiasis, including non-contrast CT of the abdomen and pelvis was negative
      for renal stones or hydronephrosis. After discharge, the patient presented one
      week later in the ED with right lower quadrant pain. Contrast enhanced CT of the
      abdomen revealed perforated appendicitis.

PMID- 22470582
TI  - Aggressive adenoid cystic carcinoma with asymptomatic spinal cord compression
      revealed by a "curtain sign".
AB  - The authors present a case of unusually aggressive adenoid cystic carcinoma of
      the head and neck. The patient presented with sciatica one year after initial
      diagnosis. She was otherwise asymptomatic. Complete work-up for bone involvement,
      included bone scan and MRI. The patient had painful osteolytic sacral metastasis
      and asymptomatic thoracic (T5) vertebral metastasis revealed by a typical curtain
      sign on MRI. The curtain sign, originally described by Trolard, is due to the
      displacement of the Trolard's membrane with the median ligament attaching the
      dura to the bone while there is a dorsal displacement and loosening of the
      posterior longitudinal ligament. The patient benefited from radiotherapy and did
      not develop respiratory distress, paraplegia or pain but died of liver
      metastases.

PMID- 22470583
TI  - Solitary epidural brain metastasis of a peripheral neuroepithelioma (a primitive
      neuroectodermal tumor): a case report.
AB  - A 14 year old male was referred to a CT scan at our hospital for evaluation of
      headache. The patient was a known case of cervical soft tissue primitive
      neuroectodermal tumor (PNET) who has undergone surgery and radiotherapy 4 years
      ago. CT scan showed a large solitary extra axial, epidural lesion in the right
      parietal region, with mass effect and bony involvement. Subsequently, surgery was
      performed and the resultant biopsy was neuroepithelioma. After diagnosis the
      patient has undergone chemotherapy and radiotherapy. He remained symptom free,
      and also follow up CT scans of the brain, chest, and abdomen were normal after
      two years post surgery. This is the first reported case of epidural metastasis of
      a head and neck (peripheral) PNET.

PMID- 22470584
TI  - Radiology is Art.

PMID- 22470585
TI  - Acral osteolysis in bilateral carpal tunnel syndrome.
AB  - Carpal tunnel syndrome is a common neurological condition with rare yet
      potentially serious cutaneous and skeletal complications. We present a case of
      mutilating/ulcerating bilateral carpal tunnel syndrome in a 63 year old female.
      Radiographs showed symmetrical acral osteolysis in the index and middle fingers
      distal phalanges bilaterally. Carpal tunnel decompressions provided symptomatic
      relief.

PMID- 22470586
TI  - Visualization of Noncalcified Gallstones on CT Due to Vicarious Excretion of
      Intravenous Contrast.
AB  - We present a case where low attenuation gallstones are visible on CT only on
      delayed imaging secondary to gallbladder opacification from vicarious excretion
      of contrast. We discuss heterotopic accumulation of contrast in the gallbladder
      and its potential diagnostic utilization in the detection of occult pathology.

PMID- 22470587
TI  - Pulmonary Embolism following Endovenous Laser Ablation (EVLA) of the Great
      Saphenous Vein.
AB  - A 70yr old lady presented to accident and emergency with sudden onset pleuritic
      chest pain. A pulmonary embolus (PE) was diagnosed by CTPA. Ten days earlier she
      had bilateral EVLA for recurrent great saphenous vein disease. Confounding risk
      factors for pulmonary embolism included bilateral ligation and stripping of the
      great saphenous vein a year earlier, malignancy, EVLA and phlebitic tributary
      varices. EVLA has been shown to be an effective treatment for superficial venous
      insufficiency with low morbidity and high patient satisfaction. The investigation
      of confounding risk factors and possible causes should not compromise the initial
      treatment of PE.

PMID- 22470588
TI  - An unusual complication of an infiltrated intravenous catheter: heterotopic
      ossification in a newborn.
AB  - Heterotopic ossification refers to formation of lamellar bone in soft tissues.
      The etiology is diverse and includes genetic, post-traumatic, and metabolic
      causes. Elicitation of bone morphogenic proteins are thought to play a key role
      in the pathogenic process. Initially, heterotopic ossification presents a
      clinical and radiographic challenge in that it can be mistaken for other more
      worrisome entities which present with calcified soft tissue masses. However, a
      spontaneous clinical resolution, temporal relationship to an inciting agent, and
      radiographic evolution to a peripherally-calcified lesion are all clues to the
      diagnosis. Here we present the clinical and radiographic features of heterotopic
      ossification as a result of an infiltrated peripheral IV.

PMID- 22470589
TI  - Radiology from a "different" view.
AB  - This editorial is dedicated to a radiologist who makes diagnostic imaging more
      appealing to the viewer's eye with special post-processing techniques.

PMID- 22470590
TI  - Emperor's Newest Clothes.

PMID- 22470591
TI  - Moyamoya disease - a vasculopahty and an uncommon cause of recurrent
      cerebrovascular accidents.
AB  - Moyamoya disease is a very rare chronic cerebrovascular disease of unknown
      etiology characterized by recurrent ischemic or hemorrhagic strokes. Initially
      diagnosed in Japan and named after finding puff of smoke like collateral blood
      vessels around the occluded blood vessels of circle of Willis. With increase
      awareness this disease is now diagnosed more often. Medical and surgical
      treatment have been used to treat the disease, with surgical treatment been
      mostly experimental. Special attention should be given to the surgical treatment
      which has shown to have an edge over the medical treatment in some clinical
      trials especially in young patients with recurrent strokes to prevent progressive
      cognitive decline and to improve their quality of life. In our patient, who is a
      young man, the diagnosis was picked up late and when surgical evaluation was
      performed, it was considered to be fruitless with findings of nonviable brain
      tissue on MRI imaging.

PMID- 22470592
TI  - Cavitating lung lesions in chronic thromboembolic pulmonary hypertension.
AB  - PURPOSE: The aim of this study is to assess the incidence and natural history of
      cavitating lung lesions in chronic thromboembolic pulmonary hypertension (CTEPH),
      note thrombus position between patients with and without a cavity and determine
      whether their development is a predictor of mortality.  MATERIALS
      #ENTITYSTARTX00026; METHODS: All patients with confirmed CTEPH attending our
      Pulmonary Vascular Unit between February 1998 and January 2006 were identified,
      and a review of their notes and imaging was performed. Thrombus position, pre
      disposing factors, cavity progression and mortality were noted, and comparisons
      made between those with and without a cavity. RESULTS: 11 of 104 patients had a
      cavity (10.6%). Thrombus distribution was similar between those with and those
      without a cavity. Preceding infection was not proven in most cases. 27.3% of
      patients with a cavity died compared to 26.8% of those without. CONCLUSION:
      Cavity formation in CTEPH is 3 times more common than in acute pulmonary
      embolism. Thrombus position does not predict cavity development, and the presence
      of a cavity may serve as an indicator of disease severity but does not appear to
      predict mortality.

PMID- 22470593
TI  - Thoracic peri-aortic fibrosis in a patient of psoriasis - Cyclosporine as a
      putative etiologic agent.
AB  - The article describes an unusual occurrence of peri-aortic fibrosis with
      consequent luminal stenosis in descending thoracic aorta in an adult case of
      Psoriasis. The report also illustrates the role of Multi-detector CT in the
      diagnosis of thoracic peri-aortic fibrosis. The patient had received cyclosporine
      on multiple occasions during acute exacerbation of disease. In absence of any
      concomitant infective-inflammatory system disorder or atherosclerotic process,
      the cyclosporine is suggested as a putative etiologic agent for peri-aortic
      fibrosis.

PMID- 22470594
TI  - Extra-adrenal retroperitoneal paraganglioma associated with duplication of
      inferior vena cava.
AB  - Retroperitoneal paragangliomas arise from specialized neural crest cells
      symmetrically distributed along the aorta in association with the sympathetic
      chain. If this tissue aggregates in the adrenal medulla pheochromocytoma may
      arise. When it remains in the paraaortic sites it could develop into extra
      adrenal, retroperitoneal paraganglioma. We report a case of extra-adrenal
      paraganglioma in the renal hilum intimately related to the left side of a double
      inferior vena cava. To the best of our knowledge such an association has never
      been described before. The clinical significance of this venous anomaly is
      reviewed.

PMID- 22470595
TI  - Lithium therapy: an unusual cause of elevated and diffuse radioactive iodine
      uptake.
AB  - Lithium carbonate, a widely used treatment for bipolar disorders, is associated
      with goiter, hypothyroidism and thyrotoxicosis. However, the effect of lithium to
      increase radioactive iodine uptake has received little attention, thus, making
      Lithium a confounding factor in the interpretation of thyroid radionuclide
      studies. We herein report a case of misinterpreted high radioactive iodine uptake
      in a euthyroid, lithium-treated goitrous patient. We conclude that lithium
      therapy should be considered in the etiologic diagnoses of patients with goiter
      and homogenously elevated radioiodine uptake. It is pertinent to recognize this
      phenomenon in order to prevent unwarranted treatment with radioactive iodine or
      thionamides.

PMID- 22470596
TI  - Apneic oxygenation for elimination of respiratory motion artefact in an intubated
      patient undergoing helical computed tomography pulmonary angiography.
AB  - Respiratory motion artifact in intubated and mechanically ventilated patients
      often reduces the quality of helical computed tomography pulmonary angiography
      (CTPA). Apneic oxygenation is a well established intra-operative technique that
      allows adequate oxygenation for short periods (up to 10 min) in sedated and
      paralyzed patients. We describe the use of the apneic oxygenation for elimination
      of respiratory motion artefact in an intubated patient undergoing CTPA.

PMID- 22470597
TI  - Focal nodular hyperplasia of the liver with pseudo-angiomatous appearance of the
      central area: MRI findings and physiopathological insights.
AB  - We report an unusual case of focal nodular hyperplasia (FNH) with angioma-like
      vascularity in the central scar illustrated on MRI and proven by histopathology.
      The vascular theory of common causative factors in FNH and haemangioma is
      discussed.

PMID- 22470598
TI  - Journal of radiology case reports: policy updates.
AB  - This article describes policy updates for manuscripts submitted after November
      1(st) 2008 to the interactive Journal of Radiology Case Reports.

PMID- 22470599
TI  - Bouveret's Syndrome: a Case Report.
AB  - Bouveret's syndrome is a well known clinical entity; its incidence however, is
      uncommon. An unusual complication of cholelithiasis, Bouveret's syndrome should
      be considered in an elderly patient presenting with acute gastric outlet
      obstruction.We describe a case of an elderly female patient presenting with acute
      gastric outlet obstruction secondary to a massive gallstone and discuss the
      imaging appearances and therapeutic options for this rare condition.

PMID- 22470600
TI  - An unusual congenital hepatic cyst in an adolescent and review of differential
      diagnoses of complex liver cysts.
AB  - The diagnosis of a simple hepatic cyst is not difficult, but diagnostic confusion
      occurs when atypical features such as intracystic debris or extremely large size
      are present. In children, simple liver cysts are described as small,
      asymptomatic, and rarely hemorrhagic. We report an adolescent male presenting
      with an unusually large hepatic cyst that did not have typical imaging
      characteristics. The imaging findings and histology are displayed along with the
      differential diagnoses of complex liver cysts.

PMID- 22470601
TI  - Irinotecan drug eluting beads used as a treatment of advanced intra hepatic
      cholangiocarcinoma.
AB  - This report describes a 74-year-old male with unresectable intrahepatic
      cholangiocarcinoma (ICC). However surgical procedure is the only curative
      treatment, it often seems to be ineffective because of the aggressive behaviour
      of the disease. The role of systemic chemotherapy in the ICC is undefined with a
      median survival between 6.43 to 12.17 months obtained by using the combination
      chemotherapy of gemcitabine with cisplatin. In the present case, we performed a
      targeted treatment using drug eluting beads (DEB) with irinotecan (IRI)
      administered as transarterial-chemoembolization (TACE). After one session, the
      tumour vascularity decreased significantly at the one month evaluation on
      computed tomography (CT) scan of the liver. This case report suggested that
      minimally invasive transcatheter DEB embolization could be a promising, safe and
      effective treatment for selective patients with unresectable ICC.

PMID- 22470602
TI  - Radiology goes gothic.

PMID- 22470604
TI  - Primary Burkitt's Lymphoma Of The Appendix Presenting As Acute Abdomen: A Case
      Report.
AB  - Leukemic and lymphomatous involvement of the appendix is rare and even rarer is
      its presentation as appendicitis. Burkitt's lymphoma is a high grade B-cell
      neoplasm. Its non-endemic form typically presents as abdominal mass in children.
      This rapidly growing tumour may cause symptoms due to mass effect or direct
      involvement of the bowel. Clinical presentations like acute abdomen can be
      secondary to intestinal obstruction, intussusception or sometimes perforation.We
      describe here a case of an adult male with an unusual presentation of appendiceal
      Burkitt's lymphoma mimicking acute cholecystitis or appendicitis.

PMID- 22470603
TI  - Synchronous primary tumors of the kidney and the ovaries: Imaging findings.
AB  - The simultaneous presence of primary carcinomas in the same patient is uncommon
      and synchronous primary tumors involving the kidney and ovary are extremely rare.
      There are a few reports in the English literature of synchronous primary
      malignancies of the kidney and the ovaries, but no data regarding their imaging
      features. We present a case of an elderly woman, diagnosed with bilateral ovarian
      clear cell carcinomas and a simultaneous clear cell carcinoma of the right
      kidney, evaluated by multidetector CT and MR imaging.

PMID- 22470605
TI  - Jejunal diverticulitis: an unusual cause of an intra-abdominal abscess - coronal
      Computed Tomography reconstruction can aid the diagnosis.
AB  - Jejunal diverticulitis is a rare condition that can present with an acute abdomen
      and be referred for imaging. We present the case of an elderly patient who at CT
      was diagnosed with an intra-abdominal abscess involving both jejunum and
      transverse colon. However, the underlying eitiology was not initially clear until
      small bowel barium follow-through.Pertinent points regarding CT findings in
      jejunal diverticulitis are discussed, and practical recommendations in small
      bowel diverticulum recognition and diagnosis are made.

PMID- 22470606
TI  - Diagnosis of variants of single right coronary trunk using 64 multidetector
      computed tomography.
AB  - Single coronary anomalies are one of the rarest variants of coronary anatomy.
      Widespread use of coronary CT angiography has made it possible to diagnose these
      variants with increasing incidence. We report two cases of single right coronary
      trunk with different anatomic course of the left coronary artery; one anterior to
      the main pulmonary artery and the second between the main pulmonary artery and
      ascending aorta and then coursing within the interventricular septum.

PMID- 22470607
TI  - Bilateral carotid artery dissection after high impact road traffic accident.
AB  - A 58 year old man was involved in a high impact road traffic incident and was
      admitted for observation. Asymptomatic for the first 24 hours, he collapsed with
      symptoms and signs consistent with a cerebrovascular accident. Computed
      tomography angiogram (CTA) and Magnetic resonance angiogram (MRA) demonstrated
      bilateral internal carotid artery dissections and a left middle cerebral artery
      infarct. It was not considered appropriate to attempt stenting or other
      revascularistation. The patient was treated with heparin prior to starting
      warfarin. He made a partial recovery and was discharged to a rehabilitation
      facility. This case is a reminder of carotid dissection as an uncommon but
      serious complication of high speed motor vehicle accident, which may be silent
      initially. Literature Review suggests risk stratification before relevant
      radiological screening at risk patients. Significant advances in CTA have made it
      the diagnostic tool of choice, but ultrasound is an important screening tool.

PMID- 22470608
TI  - Ileocolic invagination as a complication of a cecal adenocarcinoma.
AB  - Ileocolic invagination in the adult may be caused by adenocarcinoma and lead to
      intestinal obstruction. We report a case of a cecal adenocarcinoma that was
      complicated by an ileocolic invagination in a 38 year old female, diagnosed on a
      contrast enhanced CT scan of the abdomen and highlights the importance of
      contrast enhanced CT for diagnosis of ileocolic invagination.

PMID- 22470609
TI  - Honoring our helpers.
AB  - This special issue of the Journal of Radiology Case Reports honors the reviewers
      who donated their time and expertise to the high quality and success of this
      journal.

PMID- 22470610
TI  - A quick look back - 2008 journal resume.
AB  - This is a quick retrospective view back to the year 2008, summarizing the
      journal's experience and demonstrating submission statistics of the Journal of
      Radiology Case Reports.

PMID- 22470611
TI  - Two Stage Complex Embolization of an Arteriovenous Fistula between the Right
      Common Iliac Artery and the Inferior Vena Cava.
AB  - We present an interesting case of a symptomatic high flow AV fistula between the
      right common iliac artery (CIA) and the inferior vena cava (IVC), successfully
      treated by endovascular coil embolization. The patient was found to have a right
      lower polar renal artery crossing the ipsilateral ureter arising from the CIA,
      causing pelvi-ureteric junction (PUJ) obstruction and recurrent pyelonephritis.
      It is hypothesized that this fistula arising from the lower polar renal artery
      and entering the IVC, may have occurred as a result of trauma during a previous
      pyeloplasty, or a pathologically induced process of angiogenesis stemming from
      recurrent pyelonephritis.

PMID- 22470612
TI  - Lateral abdominal wall hernia following blunt trauma - a rare case.
AB  - The presence of superficial bruising, no abnormal signs on abdominal examination
      and a negative FAST scan of the abdomen may not be enough to rule out intra
      abdominal pathology. We report on the usefulness of CT in diagnosing a post
      traumatic abdominal wall hernia.

PMID- 22470613
TI  - Mount Fuji sign with concavo-convex appearance of epidural haematoma in a patient
      with tension pneumocephalus.
AB  - Intracranial pneumatocele is a non-infected accumulation of air within the
      cranial cavity. We report a case of a 22-year-old male who sustained a fracture
      of anterior cranial fossa following a motor vehicle accident and the imaging
      findings showed a concave-convex epidural haematoma. Simple traumatic
      pneumocephalus usually does not require surgical treatment and non-operative
      management has been advocated for small, asymptomatic convexity extradural
      haematomas.

PMID- 22470614
TI  - Pseudotumoural gastric lesion caused by fish bone perforation.
AB  - We report the case of a 34-year-old previously fit and healthy male who presented
      to the accident & emergency department with non-specific abdominal pain. The
      patient proceeded to undergo laparotomy at which a large mass was found adjacent
      to the stomach. The impression at surgery was of a lymphoma or gastric carcinoma
      though CT had reported the likelihood of a fish bone or foreign body causing
      duodenal perforation. Histology later confirmed the presence of a fish bone
      surrounded by reactive tissue.

PMID- 22470615
TI  - Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known
      Beta Thalassemia Major.
AB  - We describe a 16 year-old male with beta thalassemia major and gait disturbances
      that had not been given blood transfusions due to a severe childhood transfusion
      reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the
      spine and epidural masses causing cord compression consistent with extramedullary
      hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored
      blood transfusions, the patient demonstrated significant improvement of his
      paraspinal lesions and near complete resolution of his neurological symptoms.
      While EMH causing cord compression in adolescents is rare in the current era of
      bone marrow transplantation or chronic transfusions, it should be considered when
      thalassemia major patients present with neurological deficits. The well defined
      imaging features of EMH can play a central role in its diagnosis and management,
      especially because surgical and / or radiotherapeutic intervention are often
      considered in cases of failed medical treatment.

PMID- 22470616
TI  - Sacral Ewing's Sarcoma and Challenges in it's Diagnosis on MRI.
AB  - A 15-yr old boy presented with low backache for 4 months associated with weakness
      of left lower limb. MRI of lumbosacral spine showed a sacral lesion with
      intraspinal and presacral soft tissue extension with neural compression. A
      diagnosis of tuberculosis was considered in the view of high prevalence in this
      part of the world, however biopsy revealed Ewing's sarcoma. Ewing's tumor of
      sacrum is rare, but should be suspected in low backache in children. Differential
      diagnosis for a sacral lesion includes tuberculosis, pyogenic osteomyelitis,
      lymphoma, chordoma, osteosarcoma and Ewing's sarcoma. MRI is sensitive in
      detecting these lesions but is nonspecific requiring histopathological
      examination for confirmation.

PMID- 22470617
TI  - Tuberculous osteomyelitis of the scapula masquerading as metastasis.
AB  - Tuberculosis (TB) of the scapula is an unusual presentation of musculoskeletal
      tuberculosis. In an endemic area, this rare presentation may become more
      frequent. The indolent nature of tuberculous bone and joint disease often leads
      to delayed or missed diagnosis. It is not uncommon for this disease to mimic
      malignancy. Therefore, the prompt recognition of distinguishing features is vital
      for correct diagnosis. In particular, imaging is a key tool in helping to make
      the diagnosis, through the recognition of certain key radiological patterns.
      However, as there are no pathognomonic imaging findings, the diagnosis rests on
      histopathological and microbiological confirmation. We report a case of
      tuberculous osteomyelitis of the scapula. This entity has not received much
      attention in literature. Pure tuberculous osteomyelitis involving flat membranous
      bone, as depicted in this report, is rare. Our patient also had an ovarian
      malignancy, which had decreased our index of suspicion. We therefore present this
      case as tuberculosis masquerading a cystic scapular metastases.

PMID- 22470618
TI  - Congenital hearing loss explained in adulthood. Computed tomography of the
      temporal bone in hemifacial microsomia. A case report.
AB  - We present a case of complex hemifacial microsomia (HFM) which was diagnosed at
      the age of 46 years. Imaging findings of a complex deformity of the temporal bone
      are presented and connected to a broad range of clinical symptoms. Computed
      tomography (CT) imaging indications are discussed briefly.

PMID- 22470619
TI  - Renal lymphangiectasia presented by pleural effusion and ascites.
AB  - A young male patient complaining of vague abdominal pain, dyspnea, generalized
      weakness and abdominal distension for 6 months was referred for abdominal
      ultrasound. Ultrasound showed enlarged echogenic kidneys, perinephric and renal
      sinus cystic fluid collections bilaterally with ascites and right pleural
      effusion. The ultrasound findings were confirmed by abdomen CT scan. Renal
      function test was within normal. Laboratory analysis of aspirated perinephric
      fluid revealed abundant lymphocytes. The radiological findings and perinephric
      fluid aspiration analysis are consistent with renal lymphangiectasia. Pleural
      effusion, in addition to ascites and perinephric fluid collections, is a new
      presentation of the disease. Ascites and pleural effusion were improved by
      diuretics.

PMID- 22470620
TI  - Gastrointestinal amyloidosis presenting as enterocolitis on abdominal CT scan.
AB  - The imaging findings of amyloidosis are nonspecific and diverse due to its
      association with various chronic diseases such as multiple myeloma. We report a
      case of gastrointestinal amyloidosis presenting as enterocolitis on a contrast
      enhanced CT scan of the abdomen.

PMID- 22470621
TI  - An atypical case of noninfected iliopsoas bursitis - MRI findings.
AB  - The authors present an unusual case of atypical iliopsoas bursitis in an 81 years
      old female patient. The patient asked for medical advice due to a chronic left
      hip and lower abdominal pain with no specific characteristics. Physical
      examination revealed a palpable left-sided pelvic mass. Ultrasound examination
      demonstrated a purely cystic mass that was presumed to be an ovarian cystic
      malignancy. The patient was referred for an MRI examination, which showed a
      cystic lesion extending from the left iliac crest to the anterior aspect of the
      ipsilateral hip joint (maximum diameter 18 cm), coursing below the iliopsoas
      tendon indicative of an extremely distended iliopsoas bursa.

PMID- 22470622
TI  - Asymmetric 18F-FDG Uptake in the Infradiaphragmatic Brown Adipose Tissue (BAT)
      Mimicking Adrenal Metastasis: A Relatively Rare Site of Brown Fat and a Potential
      Source for False Positive FDG-PET Study.
AB  - FDG uptake in the metabolically active brown adipose tissue (BAT) is a source of
      significant concern while interpreting FDG-PET studies. It is also of great
      interest due to its potential implications for obesity research. In this
      communication, we describe hitherto unreported asymmetric BAT uptake in the
      abdomen, persisting after diazepam intervention in the repeat PET study on a
      separate day. The patient did not have any evidence of disease even at 24 months'
      follow up. The present case is a useful addition to the current body of
      literature of false positive FDG-PET due to BAT uptake in unusual location and
      underscores the importance of high index of suspicion and careful correlation,
      whenever one comes across an unusual PET finding in a given clinical situation.
      This assumes important diagnostic value particularly when it coexists in the
      setting of malignancy where the disease can be falsely upstaged by
      misinterpretation. The literature relevant to the report is discussed and a
      schema is suggested for correct interpretation.

PMID- 22470623
TI  - A leiomyoma in a cachectic woman presenting as a giant abdominal mass.
AB  - Fibroids are the most common gynecologic tumors. Our case discusses the outcome
      of a 47-year-old woman who presented to our clinic with cachexia, and a giant
      abdominal mass. An initial diagnostic imaging workup consisted of X-Ray, CT, and
      ultrasound and indicated a possible diagnosis of leiomyosarcoma. However, after
      surgical evaluation, she was diagnosed pathologically with an atypical
      presentation of a uterine leiomyoma. Our case reviews the epidemiology and
      presentation of both pathologies, along with the imaging workup, and the
      operative correlation in our patient.

PMID- 22470624
TI  - Dural based mass: malignant or benign.
AB  - In March 2007, a 68 year old female was diagnosed with colonic adenocarcinoma
      metastatic to the lungs and a frontoparietal parafalcine lesion suspected to be a
      meningioma was also noted. She denied neurologic symptoms and resection of the
      parafalcine lesion did not occur. For 14 months, she received chemotherapy with
      poor response. In June 2008, she developed multiple focal neurologic deficits.
      Enlargement of the parafalcine brain lesion was noted on head computerized
      tomography and magnetic resonance imaging. Cerebral angiogram demonstrated a
      parafalcine mass supplied by the middle meningeal artery. All 3 modality findings
      confirmed a meningioma. Embolization of the middle meningeal artery with
      craniotomy for excision of the suspected meningioma was performed. Pathology
      indicated metastatic adenocarcinoma with colonic primary without evidence of
      meningioma. Meningiomas are the most common dural based lesions; however, a
      variety of dural lesions mimic meningiomas. Dural metastatic tumors mimicking
      meningiomas is an uncommon phenomenon, particularly when the primary location is
      the colon. This paper additionally discusses the differentiation of benign dural
      based tumors like meningiomas from malignant findings. Multiple adjunct studies
      can differentiate meningiomas from metastatic tumor. The definitive diagnosis is
      based on histopathology.

PMID- 22470625
TI  - Lipid infusion through malpositioned central venous catheter: head ultrasound
      features.
AB  - Properly placed central venous catheters have been effective in establishing
      prolonged access for total parenteral nutrition infusion in ill neonates.
      However, malposition of the catheter may lead to lethal complications.
      Malposition and infusion into the epidural venous plexus is most commonly
      diagnosed on the basis of radiographs and has been confirmed by lumbar puncture.
      Several studies describe catheter malposition and associated complications. None,
      however, demonstrate head ultrasound features. We present sonographic findings in
      a patient who received hyperalimentation for 15 days through a malpositioned
      lower extremity peripherally inserted central venous catheter.

PMID- 22470626
TI  - Multifocal extra-adrenal myelolipoma arising in the greater omentum.
AB  - Myelolipomas are rare benign tumors composed of mature fat and hematopoietic
      elements. They are most often discovered incidentally within the adrenal glands,
      with extra-adrenal myelolipomas being extremely rare tumors. We report a case of
      multifocal omental extra-adrenal myelolipoma in a patient who had undergone
      bilateral adrenalectomy. To our knowledge, this is the first reported case of an
      intraperitoneal extra-adrenal myelolipoma.

PMID- 22470627
TI  - Complete cloacal duplication imaged before and during pregnancy.
AB  - The authors describe a 31 year-old female who presented emergently with abdominal
      pain and was found at CT to have complete genitourinary duplication including
      separate urinary bladders, uteri, cervices, and vaginas, and also duplication of
      the rectum. No etiology for abdominal pain was identified. The patient was
      referred to urology for further evaluation, and an intravenous urographic study
      was obtained, which confirmed complete lower urinary tract duplication. The
      patient presented emergently 9 months later during a subsequent pregnancy for
      further evaluation of abdominal pain. A second CT scan was ordered to rule out
      appendicitis. Findings consistent with cloacal duplication were again noted.
      There was also dilatation of the urinary collecting systems, more prominently on
      the right side. A Cesarean section was performed and confirmed total
      genitourinary and rectal duplication.

PMID- 22470628
TI  - Supernumerary testis.
AB  - Polyorchidism is a rare congenital anomaly of the genital tract in which more
      than two testes are present, usually within the scrotum. Less than 100 cases of
      polyorchidism have been reported in medical literature till date. The most common
      form is the presence of three testis referred as triorchidism or tritestis. There
      are characteristic sonographic features of polyorchidism, and the diagnosis is
      often made on the basis of ultrasonography. Magnetic resonance imaging can be
      used for confirmation. We present a case of polyorchidism in a 13 yrs old
      adolescent.

PMID- 22470630
TI  - The "nature" of radiography.
AB  - This editorial is dedicated to an academic surgeon who has developed and
      sophisticated radiographic techniques to make art out of nature over the last 40
      years.

PMID- 22470629
TI  - Expansive Masses Arising From The Clivus: The Role Of FDG-PET/CT In The Metabolic
      Assessment Of Skeletal Lesions.
AB  - A patient with neurological symptoms underwent CT scan that showed a sellar and
      suprasellar mass with bone erosions, involving especially the clivus and the
      right petrous apex. The first diagnostic hypothesis was chordoma in relation to
      the mass position. The MRI showed a solid well-enhancing mass; moreover another
      circumscribed lesion, with similar signal pattern, was found in the left
      mandibular condyle. the signal and the presence of another lesion did not agree
      with diagnosis of chordoma. FDG-PET/CT study showed multiple pathological uptakes
      suggesting a metastatic disease. A trans-sphenoidal excisional biopsy was
      performed and the histopathological analysis showed a population of cells
      consistent with a plasmacell tumor, confirmed by the presence of a monoclonal
      gammopathy on blood analysis. Our case suggests that FDG-PET/CT can modify the
      diagnostic and therapeutic procedures in myeloma, by evaluating the bone marrow
      involvement.

PMID- 22470631
TI  - Pictorial review: Imaging features of unusual patterns and complications of
      hydatid disease.
AB  - Hydatid disease is a worldwide zoonosis produced by the larval stage of the
      Echinococcus tapeworm. We demonstrate rare locations and unusual complications of
      this entity during past 6 years. Rare locations during our observation included
      lumbar spine, sacral spine, spleen, ovary, abdominal wall, diaphragm, pelvis and
      right kidney. Unusual complications included formation of bronchopulmonary
      fistula, complete collapse of left lung secondary to hilar location of Hydatid
      cyst and hydatiduria.

PMID- 22470632
TI  - Orbital Roof "Blow-in" Fracture: A Case Report and Review.
AB  - We report a relatively rare case of an essentially isolated orbital roof "blow
      in" fracture in a pediatric patient. A 13-year-old male presented with headache
      and nausea following blunt facial trauma sustained during a skate boarding
      accident. CT head revealed soft tissue swelling and an abnormal bony density in
      the superior, posterior right orbital region. Follow-up CT orbits revealed a
      comminuted orbital roof "blow-in" fracture with involvement of the ethmoid air
      cells and two tiny foci of intracranial air. Expert consultation revealed normal
      ophthalmologic and neurologic examination; conservative management was
      recommended. The case report is followed by a brief overview of orbital fractures
      including pertinent radiographic considerations.

PMID- 22470633
TI  - A case report of a giant presacral cystic schwannoma with sigmoid megacolon.
AB  - Schwannomas are peripheral nerve sheath tumours with a slow growth rate. Giant
      sacral schwannoma with anterior cortex erosion and associated intrapelvic
      extension are uncommon. Though they tend to be large when initially found, most
      Giant schwannomas are clinically asymptomatic. The tumour appears heterogenous
      due to long standing degeneration. Herein, we present a case of a large purely
      cystic presacral schwannoma in a patient with poliomyelitis, which has displaced
      adjacent organs including urinary bladder and sigmoid colon, with an initial
      presentation of constipation. The tumour was partially excised and diagnosis was
      confirmed by histo-pathology and immunohistochemistry.

PMID- 22470634
TI  - Osteopoikilosis: a case report of a symptomatic patient.
AB  - Osteopoikilosis (OP) is a very rare benign sclerosing bony dysplasia with an
      autosomal dominant inheritance. We describe the morphology of an osteopoikilosis
      male patient, associated with severe pain on wrist and hand joints, report on the
      relative literature and focus on clinical significance, due to mimicking
      capability of other more severe conditions such as bone metastases.

PMID- 22470635
TI  - Esophageal actinomycosis: a case report and review of radiographic findings.
AB  - Esophageal Actinomycosis is a rare disease with only two previous reports in the
      Radiology literature. We present a 27 year-old African American male with a past
      medical history of a renal transplant for renal disease secondary to lupus who
      presented with odynophagia. The computed tomography and barium swallow findings
      are presented as well as a differential diagnosis of infectious esophageal
      diseases.

PMID- 22470636
TI  - Compensatory dilatation of the Azygos Venous system Secondary To Superior Vena
      Cava Occlusion.
AB  - Superior vena cava (SVC) occlusion can be clinically recognized in the acute
      setting when the stenosing process does not allow the development of collateral
      venous channels, which guarantee the venous drainage to the right heart. On the
      contrary, when the obstruction develops progressively, the diagnosis of SVC
      obstruction may remain undiagnosed. In the present case, the presence of SVC
      thrombosis was purely coincidental. In fact, the obstruction was first noticed on
      diagnostic tests performed because of the malfunction of a totally implantable
      Porth a Cath placed into the superior vena cava (through right subclavian
      access), five years before, in a patient suffering from non-Hodgkin disease.
      Venography is the most appropriate diagnostic methodology which reveals the
      presence of a dilated azygos vein as a compensatory mechanism. Comparison with
      computed tomography allows to confirm the diagnosis and to identify the possible
      causes. Dilatation of the azygos vein, secondary to superior vena cava
      thrombosis, although a rare event, should be taken into consideration in those
      patients with CVC and who present with frequent episodes of deep venous
      thrombosis.

PMID- 22470638
TI  - Metastatic deposit in the skull.

PMID- 22470637
TI  - Educational treasures in Radiology: Annotate - creating interactive teaching
      files.
AB  - This article focuses on Annotate (www.annotate.org) - an online program for image
      editing and creation of interactive teaching files. This program is free to use,
      does not need any installation or plugin and can be used from any workstation
      with internet access. Multiple tools and preferences allow a customization of the
      program to the user needs.

PMID- 22470639
TI  - Iodine 131 ablation of an obstructive lingual thyroid.
AB  - A 48-year-old woman undergoing surgery could not be intubated because of an
      oropharyngeal mass. CT and MRI revealed a 3 cm possible lingual thyroid mass,
      confirmed by Iodine-123 SPECT/CT. The patient underwent successful Iodine-131
      ablation and has done well on thyroid hormone-replacement therapy. This case also
      demonstrates how modern cross-sectional imaging like SPECT/CT can appropriately
      be used in the patient diagnosis and management, and is of additional interest
      for including pre- and post-therapy MRI documenting efficacy morphologically.

PMID- 22470640
TI  - Cystogram with dumbbell shaped urinary bladder in a sliding inguinal hernia.
AB  - Sliding inguinal hernias present with various symptoms and these are usually
      direct inguinal hernias containing various abdominal viscera. Case reports and
      series have been published with various organs and rare organs being part of the
      hernia. Urinary bladder is a known content of sliding hernias. This case report
      emphasizes this aspect in a picturesque manner and the importance of radiological
      investigations for pre-surgical evaluation.

PMID- 22470641
TI  - An unusual vesical calculus.
AB  - We report a 52 year old patient presenting with a bladder stone formed over a
      migrated intrauterine device (Copper-T). Her history was pertinent for
      intrauterine contraceptive (IUCD) device placement 10 years back. Investigations
      included plain ultrasound of abdomen, X-ray of abdomen, urinalysis, and urine
      culture. Ultrasound and plain X-ray of the pelvis confirmed a bladder stone
      formed over a migrated copper-T intrauterine device. The device was removed
      through suprapubic cystolithotomy. Of all the reported cases of vesical stone
      formation over a migrated IUCD, this case is unique as the patient was an elderly
      - 52 year old - female. All previously reported cases are of younger age.

PMID- 22470642
TI  - The malrotated baby - a diagnostic dilemma.
AB  - We present a case in which misinterpretation of radiological images resulted in
      an incorrect diagnosis of malrotation. This case highlights the importance of
      adequate radiological review of images and of ensuring that the clinical picture
      matches the findings. Had this not been questioned in this case the baby could
      have undergone an unnecessary operation with potential mortality and morbidity.

PMID- 22470643
TI  - Myocardial calcinosis in chronic renal failure.
AB  - The authors are presenting an 18 year old male with history of end stage renal
      disease and rejected renal transplant. In his workup echocardiogram and non
      contract CT of chest revealed diffuse endocardial and myocardial calcifications.
      Extensive cardiac calcification is a rare but important entity in relation to end
      stage renal disease as it may cause complications such as valvular dysfunction
      and fatal arrhythmia.

PMID- 22470644
TI  - Polymethylmethacrylate extrusion into the femoral nutrient vessel during
      arthroplasty: A phenomenon to be aware of.
AB  - Third generation cementing technique is now commonly used for total hip
      arthroplasty. The aim of this technique is to sufficiently pressurise the cement
      and allow maximal penetration of the cement into any remaining trabecular bone to
      provide a stable fixation of the prosthesis. We report a case where this
      pressurisation resulted in polymethylmethacrylate retrograde filling of the
      nutrient vessel and we discuss the controversial diagnosis and current literature
      surrounding this rare phenomenon.

PMID- 22470645
TI  - Intraosseus and extraosseus juxtaarticular calcification: Osteopoikilosis with
      synovial osteochondromatosis - an association.
AB  - Osteopoikilosis presents as round or ovoid sclerotic lesions with an appearance
      like enostosis on pathology. Synovial osteochondromatosis occurs due to
      cartilaginous metaplasia with synovial villous proliferation with calcified
      nodules in proximity to joints. A case of osteopoikilosis associated with
      synovial osteochondromatosis is described. Intraosseus and juxta osseus sclerotic
      bone lesions were identified on radiographs and computed tomography in a patient
      with knee pain. The association of osteopoikilosis with synovial
      osteochondromatosis is rare and to our knowledge has received little attention in
      the literature.

PMID- 22470646
TI  - Imaging features of renal hydatid cyst presenting with hydatiduria.
AB  - We report a case of renal hydatid cyst in a 25-year-old male who presented with
      hydatiduria. Intravenous pyelography revealed presence of a space-occupying
      lesion in the lower pole of right kidney with curvilinear calcifications.
      Ultrasound, computed tomography and MRI were suggestive of hydatid cyst in the
      right kidney. Patient underwent right-sided nephrectomy. Passage of hydatid cysts
      in urine is an exceedingly rare occurrence. Urinary tract involvement develops in
      2-4% of all cases of hydatid cyst. Hydatiduria is an extremely rare manifestation
      of renal hydatid cyst. We report such a case with emphasis on IVU, sonographic,
      CT and MRI findings.

PMID- 22470647
TI  - Geniculate arterial pseudoaneurysm formation following trauma and elective
      orthopaedic surgery to the knee: 2 case reports and a review of the literature.
AB  - Arterial pseudoaneurysm formation of the genicular vessels following orthopaedic
      surgery to the knee is an extremely rare occurrence. Here we report the
      successful management of two cases as a complication of total knee arthroplasty
      and a tibial interlocking nail, utilising coil embolisation by interventional
      radiological techniques and negating the need for further surgery. To our
      knowledge this is one of the few reported cases of pseudoaneurysms of the
      descending genicular artery secondary to drain placement and only the second
      following tibial interlocking nail placement.

PMID- 22470648
TI  - Percutaneous vertebroplasty and spinal cord compression: a case report.
AB  - This report describes a 60-year-old woman with intensive back pain due to
      metastatic vertebral body collapse, who underwent percutaneous vertebroplasty.
      Subsequently, the patient developed metastatic lesion extrusion into the spinal
      canal because of pressure of the cement, with compression of the left
      anterolateral spinal cord. During percutaneous vertebroplasty procedure in
      patient with malignant tumors, the complication rate increases owing to the risk
      of leakage of cement resulting from the vertebral body destruction, but as also
      seen in our case, for the extrusion of the neoplastic tissue and increase of the
      pressure in the vertebral body due to the introduction of the cement.

PMID- 22470649
TI  - Isolated cortical vein thrombosis - the cord sign.
AB  - Isolated cortical vein thrombosis is an uncommon condition and often difficult to
      diagnose, both clinically and radiologically. We report a case of a 38 years old
      man who presented with headache of new onset and clinical examination was
      unremarkable. The unenhanced brain CT did not reveal any abnormality. In view of
      unrelenting headache and partial seizures, we performed magnetic resonance
      imaging (with axial T1, T2 and gradient echo sequences, coronal FLAIR, diffusion
      weighted imaging as well as Gadolinium contrast-enhanced images) and magnetic
      resonance venography of the brain that revealed an isolated parietal cortical
      vein thrombosis with the rarely reported 'cord sign'. We report the clinical and
      radiological findings in our patient with isolated parietal cortical vein
      thrombosis.

PMID- 22470650
TI  - Spinal MRI findings of guillain-barre syndrome.
AB  - Guillain-Barre syndrome is a relatively common, acute, and rapidly progressive,
      inflammatory demyelinating polyneuropathy. The diagnosis is usually established
      on the basis of symptoms and signs, aided by cerebrospinal fluid findings and
      electrophysiologic criteria. Previously, radiologic examinations have been used
      only to rule out other spinal abnormalities. We report a case of systemic lupus
      erythematosus associated with Guillain-Barre syndrome with marked enhancement of
      nerve roots of the conus medullaris and cauda equina on MR imaging. These MR
      observations may help confirm the diagnosis of Guillain-Barre syndrome.

PMID- 22470651
TI  - Postpartum pneumoperitoneum and peritonitis after water birth.
AB  - Pneumoperitoneum (the presence of free gas in the peritoneal cavity) usually
      indicates gastrointestinal perforation with associated peritoneal contamination.
      We describe the unusual case of a 28-year-old female, who was 7 days postpartum
      and presented with features of peritonitis that were initially missed despite
      supporting radiological evidence. The causes of pneumoperitoneum are discussed.
      In the postpartum period the female genital tract provides an alternative route
      by which gas can enter the abdominal cavity and cause pneumoperitoneum. In the
      postpartum period it is important to remember that the clinical signs of
      peritonism, guarding and rebound tenderness may be diminished or subtle due to
      abdominal wall laxity.

PMID- 22470652
TI  - Osteoid osteoma of the femur: masquerading the tethered cord syndrome.
AB  - We present an illustrative case of osteoid osteoma of the femur, in an 11 year
      old male child where the clinical features were masquerading the diagnosis of
      tethered cord syndrome and lead to the delay in diagnosis.

PMID- 22470653
TI  - Detection of neoplastic meningitis in a patient with gastric cancer by thallium
      201 SPECT.
AB  - We describe the usefulness of thallium-201 SPECT in a patient with neoplastic
      meningitis (NM) from gastric carcinoma. Thallium-201 SPECT is of value for the
      diagnosis of cancer; retention of thallium-201 on delayed images strongly
      suggests malignancy. NM is a lethal, major neurologic complication of cancer. The
      standard for the diagnosis of NM is cytologic confirmation of malignant cells in
      CSF, but cytologic results are often negative (estimated false negative rate,
      50%), even when NM is strongly suspected clinically. In patients with equivocal
      findings, our findings suggest that thallium-201 SPECT is one helpful tool for
      the detection of NM, particularly when associated with signet-ring cell
      carcinoma.

PMID- 22470654
TI  - Metastatic pulmonary calcification in a patient with chronic renal failure.
AB  - Metastatic pulmonary calcification characterized by diffuse calcium deposition in
      the lungs is known to occur in patients with chronic renal failure. We present a
      case of a 47-year-old man with chronic renal failure presented with dyspnea, high
      resolution computed tomography of the chest revealed multiple, centrilobular,
      calcified nodules and patchy areas of ground-glass opacity throughout both lungs,
      consistent with metastatic pulmonary calcification. Calcification was also seen
      in the bronchi and trachea.

PMID- 22470655
TI  - Cemento-ossifying Fibroma Of Paranasal Sinus Presenting Acutely As Orbital
      Cellulitis.
AB  - Fibro-osseous lesions of the face and paranasal sinuses are relatively uncommon.
      These lesions have overlapping clinical, radiologic and pathologic features
      causing difficulty in diagnosis. Neoplastic fibro-osseous paranasal sinus lesions
      can be benign or malignant. The benign fibro-osseous lesions described are:
      ossifying fibroma (and its histologic variants) and fibrous dysplasia. The
      variants of ossifying fibroma differ in the nature of calcified material (i.e.
      cementum versus bone), in the location of the lesion (oral versus paranasal sinus
      or orbital), other morphologic variations (presence of psammomatoid concretions)
      and biologic behavior (aggressive versus stable). Presence of cementum or bone
      classifies the lesion as cementifying fibroma or ossifying fibroma respectively
      while lesions with mixture of both cementum and bone are called cemento-ossifying
      fibroma. We describe a case of a young adult male with cemento-ossifying fibroma
      of paranasal sinus presenting acutely as left orbital cellulitis with proptosis.

PMID- 22470656
TI  - McKusick-Kaufman Syndrome: Atretic Upper Vaginal Pouch; an Unusual Urogenital MR
      Finding.
AB  - McKusick-Kaufman syndrome is a rare autosomal recessive disease diagnosed by
      polydactyly, hydrometrocolpos, and congenital heart disease. We present an
      unusual laparotomy confirmed urogenital MRI finding (atretic vaginal pouch) in a
      3-month-old girl with McKusick-Kaufman syndrome. Up to our knowledge, this MR
      finding has not been reported in the literature yet.

PMID- 22470657
TI  - The role of CT imaging in the congenital absence of a cervical spine pedicle: a
      case report and review of the literature.
AB  - The congenital absence of a cervical spine pedicle is a rare clinical condition
      which is usually picked up as an incidental finding on imaging studies performed
      on patients complaining of neck pain following trauma. It is important to
      recognize that the finding is not traumatic in origin as this has implications
      regarding the treatment. We report a case of congenital absence of a cervical
      spine pedicle and present a review of the literature.

PMID- 22470658
TI  - Calcific constrictive pericarditis demonstrated on 99mTc-MDP bone scintigraphy.
AB  - The authors present a case of calcific constrictive pericarditis, imaged with
      bone scintigraphy. The patient presented with three months of shortness of
      breath, chest pain, and chest tightness during exercise, among other nonspecific
      symptoms. Although the diagnosis was made based on chest radiography and cardiac
      MRI, bone scintigraphy was used to corroborate the diagnosis of calcific
      constrictive pericarditis. Bone scintigraphy showed a pattern of tracer
      accumulation consistent with pericardial uptake. Calcific constrictive
      pericarditis was also confirmed at the time of surgery.

PMID- 22470659
TI  - Solitary fibrous tumor of pleura: a case report and review of clinical,
      radiographic and histologic findings.
AB  - We present a case of solitary fibrous tumor of pleura (SFTP) in a 63-year-old
      male. Clinical manifestations of this entity, including paraneoplastic syndromes,
      are discussed, albeit absent in our presented case. Furthermore radiographic
      findings and pathologic correlations are provided. SFTP remains a rare neoplasm
      for which radiographic features are suggestive yet nonspecific, and
      immunohistochemistry remains as the diagnostic method of choice.

PMID- 22470660
TI  - A Jejunal Gastrointestinal Stromal Tumour: an unusual cause of massive acute
      gastrointestinal haemorrhage with emphasis on pre intervention MDCT.
AB  - Gastrointestinal stromal tumors (GIST) most commonly arise from the stomach
      followed by the small intestine and are common cause for an occult
      gastrointestinal (GI) bleeding. We present an unusual case of a jejunal GIST,
      which presented as an acute gastrointestinal haemorrhage. This case highlights
      the importance of an intravenous contrast enhanced abdominal CT with neutral oral
      contrast for the assessment of gastrointestinal bleeding where non-obstructive
      enhancing tumour, active extravasations and arteriovenous malformations (AVM)
      could potentially be obscured by the use of positive oral contrast. This case
      also emphasizes on the use of multiplanar image reconstructions that are
      extremely useful in determining the exact location and size of the pathology.

PMID- 22470661
TI  - Hydatid cysts in abdominal wall and ovary in a case of diffuse abdominal
      hydatidosis: Imaging and pathological correlation.
AB  - We report a case of diffuse abdominal hydatidosis with correlation of imaging
      findings with gross pathology. The patient had involvement of liver, diaphragm,
      pelvic cavity, ovary and abdominal wall. Hydatid cysts were morphologically
      different from each other including calcified, uniloculated and multiloculated
      cystic lesions. Our case is rare as ovary and abdominal wall involvement is
      described in less than 1 % cases of hydatid disease.

PMID- 22470662
TI  - Lacuna skull.

PMID- 22470663
TI  - Banding and Step-Stair Artifacts on the Cardiac-CT Caused By Pseudo-Ectopic
      Beats.
AB  - Step-stair and banding artifacts may result from irregular ventricular rhythm
      caused by atrial fibrillation or premature ectopic ventricular contractions. In
      the case reported here, severe banding and misalignment artifacts occurred due to
      electrocardiographic noise mimicking ectopic beats. Severe EKG noise or pseudo
      ectopic beats may cause rare but serious artifacts during cardiac-CT acquisition.
      Vendor-provided software for correcting ectopic beats can be used to remove
      pseudo-ectopic beats and eliminate artifacts caused by the EKG noise. All efforts
      should be made to prevent this kind of problem from happening in the first place.

PMID- 22470664
TI  - Delayed presentation of a vertebral arterio-venous fistula secondary to
      penetrating cervical trauma: endovascular management using coil embolisation - a
      case report.
AB  - Vertebro-vertebral arteriovenous fistulae occur infrequently. We report on such a
      case with delayed presentation following penetrating neck injury. This was
      successfully treated via coil embolisation. A 40-year-old woman presented with a
      subjective tinnitus that was abolished by turning her head to the right. She had
      sustained penetrating neck trauma 6 months earlier. Doppler Ultrasound and
      magnetic resonance angiogram confirmed the presence of a vertebral arterio-venous
      fistula. Using a trans-femoral arterial approach, the left vertebral artery was
      embolised by deployment of multiple coils. The patient had no return of symptoms
      at 3 months follow up. Radiological diagnosis and endovascular management of this
      condition is discussed.

PMID- 22470665
TI  - A giant heterogeneous abdominoscrotal mass: haemorrhagic hydrocele.
AB  - A hydrocele is a collection of fluid in the space surrounding the testicle
      between the layers of the tunica vaginalis. Occasionally the scrotal hydrocele
      may extend through the inguinal canal, deep inguinal ring, and into the abdomen
      as an abdominoscrotal hydrocele. Traditionally, abdominoscrotal hydrocele have
      been evaluated and diagnosed with US. However if a relationship between the
      abdominal mass and the hydrocele is not clearly defined by sonography, the
      traditional modality for imaging the abdomen and the scrotum such as CT or MRI,
      should be considered because it can be difficult to clearly delineate the anatomy
      and the full extent of the abnormality. We present a rare case of a giant
      hemorrhagic abdominoscrotal hydrocele in a 24 year old man that required an
      elective operative laparotomy for complete excision of the abdominolscrotal mass.

PMID- 22470666
TI  - Significance of reversal of diastolic blood flow in the evolution of testicular
      infarction as a complication of epididymo-orchitis.
AB  - We report a case of a 50-year-old male who presented to the Emergency Department
      and was diagnosed with epididymo-orchitis. Sonographic evaluation of the testicle
      initially showed a normal, low resistance color Doppler waveform. The patient was
      admitted to the hospital. A follow up sonogram two days later demonstrated
      reversal of diastolic arterial flow on Pulse-Wave color Doppler imaging. Reversal
      of diastolic blood flow in testicular color Doppler sonography is a sign of
      impending infarction. On hospital day 6, the patient had a follow up ultrasound
      which demonstrated infarction of the testicle. Pathology confirmed the diagnosis
      and the tissue culture grew E. coli and Candida Albicans. This case documents the
      rapid progression of epididymo-orchitis with a normal spectral waveform to
      testicular infarction with reversal of diastolic blood flow on color Doppler
      imaging as a sign of impending infarction.

PMID- 22470667
TI  - Noncontrast and contrast enhanced computed tomography for diagnosing acute
      appendicitis: A retrospective study for the usefulness.
AB  - Abdominal computed tomography (CT) provides great benefits for the differential
      diagnosis in patients complaining of acute abdominal pain. However, the use of
      diagnostic X-rays is associated with the cumulative risk of cancer development.
      In order to determine the relative usefulness of noncontrast and enhanced CT with
      intravenous contrast material for diagnosing acute appendicitis, the
      retrospective analysis was performed using 247 patients (46 children and 201
      adults) with clinically suspected appendicitis, who were admitted to our hospital
      from 2002 to 2006 and underwent noncontrast or combined noncontrast and enhanced
      CT examination. Of 185 patients who were diagnosed to have acute appendicitis
      with appendiceal thickening (167 cases) or normal-sized appendix (18 cases), 73
      cases underwent noncontrast CT alone and these 73 cases could be retrospectively
      diagnosed to have appendicitis on noncontrast CT. On the other hand, 112 cases of
      these 185 patients underwent noncontrast CT followed by enhanced CT, and
      vermiform appendix was detected in 86 cases of them (86/112, 76.8%) on
      noncontrast CT. These 86 cases could be retrospectively diagnosed to have acute
      appendicitis on noncontrast CT, whereas enhanced CT was required to detect
      vermiform appendix and to obtain the final diagnosis of appendicitis in the
      remaining 26 cases (26/112, 23.2%). Enhanced CT was superior to noncontrast CT in
      diagnosing appendicitis in all age and any gender groups. We suggest that
      enhanced, but not noncontrast, CT should be primarily performed for diagnosing
      acute appendicitis in all patients to minimize the radiation exposure unless
      intravenous administration of contrast material is contraindicated.

PMID- 22470668
TI  - Importance of CT in Evaluating Internal Hernias after Roux-en-Y Gastric Bypass
      Surgery.
AB  - As the incidence of obesity increases, laparoscopic Roux-en-Y gastric bypass
      (REYGB) surgery has become a surgical option for many patients. Although the
      laparoscopic Roux-en Y procedure has been shown to reduce weight and improve
      diabetes, hyperlipidemia, hypertension and sleep apnea, it is not without
      significant risks, as more than 10% of patients who undergo this procedure have
      postoperative GI complications. This is a case of a 51 year old man who presented
      with diffuse abdominal pain one month status-post Roux-en-Y gastric bypass. CT
      imaging proved to be crucial in the diagnosis of this pathology with small bowel
      volvulus and ischemia. We review some key CT findings that can aid clinicians in
      diagnosing internal hernias since this complication is often misdiagnosed and
      have a mortality rate of more than 50%.

PMID- 22470669
TI  - Kikuchi-fujimoto disease with bilateral uveitis.
AB  - Kikuchi-Fujimoto disease (KFD), also called histiocytic necrotizing
      lymphadenitis, is rare condition that usually presents with lymphadenitis and
      fever. KFD has been associated with many infectious disease processes,
      predominantly viral. Association with systemic inflammatory processes has been
      described. Here we present a case of KFD with the rare ocular manifestation of
      bilateral anterior uveitis, and corresponding findings on magnetic resonance
      imaging (MRI).

PMID- 22470670
TI  - Median palatine cyst.
AB  - Median palatine cysts are rare, non-odontogenic fissural cysts of the hard
      palate. These cysts occur in the midline of the hard palate, behind the incisive
      canal. Only two case reports have documented these cysts on multi-detector
      computed tomography (MDCT), neither giving detailed descriptions of the cysts.
      Knowledge of their existence is important and should not be confused with
      malignant tumors. We present the first case describing the MDCT characteristics
      of the median palatine cyst.

PMID- 22470671
TI  - Tracheal agenesis - a report of two cases.
AB  - Tracheal agenesis is a rare and in most cases lethal anomaly. It may be suspected
      because of lack of audible crying, and is often diagnosed right after birth with
      water soluble contrast medium injected into the oesophagus. We report two cases
      which were identified at our institution in the last 10 years. Imaging studies
      and medical records were reviewed in both cases. Patient number one was studied
      with a single slice computed tomography, patient number two with multislice
      detector computed tomography (MDCT) with 64 rows. The advantage of MDCT in
      demonstrating the rare condition of tracheal agenesis and with the same
      examination showing other coexisting anomalies is discussed. CONCLUSION: MDCT
      with 64 rows is an excellent diagnostic tool in diagnosing tracheal agenesis and
      showing other coexisting anomalies at the same time.

PMID- 22470672
TI  - A radiological chronicle of the presentation and management of a long gap
      oesophageal atresia.
AB  - Long gap oesophageal atresia is a clinically and technically challenging
      condition to manage. Documentation of the gap between the upper and lower pouches
      is critical to deciding the timing and feasibility of a primary anastamosis.
      Integral to this process is the role of radiology. We present a case of long gap
      oesophageal atresia accompanied by chronological radiography demonstrating its'
      staged management and highlighting some common complications.

PMID- 22470673
TI  - Mesenchymal cystic hamartoma of the liver: MR imaging with pathologic
      correlation.
AB  - This report describes a case of mesenchymal cystic hamartoma of the liver with
      diagnostic imaging work-up using only ultrasound and MRI. We demonstrate an
      approach starting from the pediatrician's physical exam culminating in surgical
      resection and pathologic confirmation with an emphasis on MR imaging.

PMID- 22470674
TI  - Fetal acrania - prenatal sonographic diagnosis and imaging features of aborted
      fetal brain.
AB  - We report a 35 year old female patient referred to our ultrasound department to
      rule out congenital anomalies. The fetus was found to have a completely formed
      brain, base of the skull and facial structures but lacking a cranium. The fetus
      was therapeutically aborted. We correlated our antenatal sonographic findings
      with gross pathological features and CT Scan of the fetal head. Despite an
      extensive search, CT features of aborted fetal brain and base of skull were not
      found in the literature.

PMID- 22470675
TI  - CT and 111In-pentetreotide SPECT of hilar ACTH-producing neuroendocrine tumor
      associated with Cushing's syndrome and massive bilateral adrenal gland
      hyperplasia.
AB  - We present the clinical, laboratory, computed tomography (CT), single photon
      emission computed tomography (SPECT), and histopathological findings of a patient
      with adrenocorticotropic hormone (ACTH) dependent Cushing's syndrome with massive
      bilateral adrenal gland hyperplasia due to a hilar ACTH-producing well
      differentiated neuroendocrine carcinoma.

PMID- 22470676
TI  - Extraspinal findings on lumbar spine MR imaging.
AB  - Interpretation of radiologic studies requires vigilance on the part of the
      radiologist to identify findings and abnormalities outside the region of
      interest. In the case of routine lumbar spine MRI for low back pain, many
      extraspinal abnormalities can often be identified. Some of these findings may
      account for low back pain. Other findings are incidental, but may have
      significant clinical implications, and are important to recognize. We present
      twenty-four examples of incidental findings from lumbar spine MRI examinations.
      The findings involve various organ systems, covering a broad range of clinical
      urgency.

PMID- 22470677
TI  - Survival to the age of 87 years in a woman with unoperated tetralogy of Fallot.
AB  - Tetralogy of Fallot is the most common cyanotic congenital heart defect,
      affecting approximately 2700 infants per year born in the United States. The
      natural history of the tetralogy reflects the adverse physiologic consequences of
      the underlying structural abnormalities, with only approximately 3% of
      uncorrected patients surviving past age 40. In this case report, we report an 87
      year-old woman with unoperated tetralogy of Fallot, who we believe to be the
      oldest and only second octogenarian described in the literature.

PMID- 22470678
TI  - Testicular relapse of non-Hodgkin Lymphoma noted on FDG-PET.
AB  - Testicular relapse of leukemia and lymphoma is a well-recognized phenomenon, with
      testicular relapse of lymphoma being more common in the adult population and
      leukemia relapse being more common in the pediatric population. With the advent
      of F-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the
      evaluation of lymphoma it is possible to evaluate testicular uptake of FDG and to
      detect primary testicular lymphoma or testicular relapse on the FDG-PET
      examination. Testicular relapse of non-Hodgkin lymphoma (NHL) detected on FDG-PET
      has been reported previously. We report an additional case in which there was
      testicular activity at presentation, a response to therapy (orchiectomy not
      performed) and then testicular relapse followed by orchiectomy. We review the
      literature with regard to testicular recurrence and testicular uptake of FDG-PET.
      There have been studies that have examined normal standardized uptake value
      maximum (SUVmax) values in the testicle, with normal values ranging from 2.81 (30
      39 years) to 2.18 (80-89 years), depending upon age. However, it should be noted
      that there could be considerable variability in SUVmax values depending upon the
      units used (e.g. normalized to lean body mass vs. body weight) and depending upon
      examination variables such as dietary conditions, muscle uptake or extravasation
      of FDG. Elevated activity or lateralizing activity should be viewed with
      suspicion, with etiologies including primary testicular tumor, primary or
      secondary testicular lymphoma and metastatic disease with other etiologies less
      likely.

PMID- 22470679
TI  - Symptomatic calvarial cavernous hemangioma: presurgical confirmation by
      scintigraphy.
AB  - Hemangiomas are rare tumors in the calvarium and represent 2% of osseous
      calvarial lesions. Dynamic Tc-99m RBC blood pool scintigraphy has a high positive
      predictive value for cavernous hemangiomas of the liver. This scintigraphic
      technique can be used for identifying cavernous hemangiomas at other anatomic
      sites. We present a case in which a tagged RBC blood pool scan was used for
      further characterizing a symptomatic calvarial lesion as a cavernous hemangioma.
      This avoided an unnecessary workup for metastatic disease and was valuable in
      surgical planning for anticipated increased intra-operative blood loss.
      Histological confirmation of a cavernous hemangioma was made after surgical
      resection.

PMID- 22470680
TI  - Epiploic appendagitis in a female patient with situs ambiguous abnormality.
AB  - We report the case of a 23 year-old obese female, with previously diagnosed situs
      inversus below the diaphragm, who presented with severe left upper quadrant
      abdominal pain. The patient was believed to have a surgical indication, possibly
      appendicitis or diverticulitis, and had an emergent abdominal Computed Tomography
      (CT) scan. The CT was interpreted as epiploic appendagitis with no signs of
      appendicitis. Epiploic appendagitis is a rare cause of acute abdominal pain,
      which involves the torsion and eventual necrosis of one of the epiploic
      appendages. This case was complicated by the fact that the patient had situs
      inversus below the diaphragm, which made it difficult to relate her localized
      abdominal pain to the correct anatomic area. The diagnosis allowed the patient to
      avoid invasive surgery and instead opt for conservative medical management. The
      utilization of radiologic imaging is of utmost importance in diagnosing this
      condition, which has characteristic findings on CT, US, and MR, all of which is
      discussed in this article.

PMID- 22470681
TI  - The Coumadin Ridge: An Important Example of a Left Atrial Pseudotumour
      demonstrated by Cardiovascular Magnetic Resonance Imaging.
AB  - A coumadin ridge is an occasionally observed, but seldom described structure seen
      in the left atrium during cardiac magnetic resonance (CMR) imaging. In this case,
      the coumadin ridge was particularly prominent and could easily have been mistaken
      for a tumour or thrombus. Using the combined assessment from different CMR pulse
      sequences, we were able to correctly identify it as the coumadin ridge. We make
      the reader aware of the location and the CMR imaging features of this structure
      so that misdiagnosis may be avoided.

PMID- 22470682
TI  - Spontaneous isolated superior mesenteric artery dissection - Report of two cases.
AB  - Two cases of isolated superior mesenteric artery dissection diagnosed by contrast
      enhanced 64 slice CT are reported. In both, the dissection was seen extending
      along the entire length of the artery with one of them showing partially
      thrombosed false lumen. One case was associated with dissection of left renal
      artery with consequent renal infarcts. Although superior mesenteric artery
      dissection is a rare phenomenon, it should be considered in the differential
      diagnosis of abdominal angina.

PMID- 22470683
TI  - Unilateral tibia vara in a toddler caused by focal fibrocartilaginous dysplasia.
AB  - Focal fibrocartilaginous dysplasia (FFCD) of the tibia is a rare tumor like
      lesion probably caused by a failure of differentiation in the pes anserinus area.
      The children usually present with unilateral tibia vara and conspicuous walking
      features. The radiographic appearance of FFCD is pathognomic. In most cases this
      benign condition undergoes spontaneous resolution. Curettage or corrective
      osteotomy is only indicated when the deformity is persistent or progressive. We
      report the case of a 14 months old toddler diagnosed with FFCD. The
      characteristic radiographic and MRI features are presented. Further, we present
      for the first time the sonographic appearance of FFCD.

PMID- 22470684
TI  - SPECT/CT imaging of a retroperitoneal nodule in a patient with history of
      infiltrating renal urothelial carcinoma.
AB  - A 62 year old woman status post radical nephroureterectomy for high grade
      urothelial carcinoma was found on CT to have a 1 cm retroperitoneal nodule in the
      nephrectomy bed. The nodule's differential diagnosis included recurrent
      urothelial carcinoma versus relocation of the patient's splenule seen on earlier
      CT imaging. We report using SPECT/CT with Tc-99m labeled denatured red blood
      cells to definitively diagnose the nodule as a relocated splenule.

PMID- 22470685
TI  - Glioblastoma of the optic pathways: An Atypical case.
AB  - We present a case of glioblastoma multiforme of the optic pathways in a 68 year
      old lady. Glioblastomas of the optic pathways are rare tumors; the predominant
      non enhancing component and the vast extent of involvement makes this a unique
      case. This case report further increases the database of knowledge available on
      the MRI characteristics of malignant optic glioma of adulthood.

PMID- 22470686
TI  - Thoraco-abdominal Aorta Dissection: Look Again Before You Leap.
AB  - Aortic dissection is a life-threatening condition that might require immediate
      assessment and therapy. We present the case of a 71-year-old woman with essential
      hypertension complaining about low back pain; unenhanced thoracic-lumbar spine
      computed tomography examination (CT) revealed a hyperdense thin line across the
      aorta with an appearance of "double aortic lumen". Enhanced CT scan confirmed the
      diagnosis of type B aortic dissection. Radiologists should be familiar with this
      finding that could be considered a new radiological sign of aortic dissection on
      unenhanced CT examination.

PMID- 22470687
TI  - Educational treasures in Radiology: Radiolopolis - an international Radiology
      community.
AB  - THIS ARTICLE FOCUSES ON A RELATIVELY NEW CONCEPT IN THE INTERNET: "Social
      networking" and especially on one program that successfully found a unique way to
      provide a social network for Radiology: Radiolopolis. Radiolopolis
      (www.Radiolopolis.com) is an international Radiology network to promote
      education, research and clinical practice in Radiology. What makes this Radiology
      community unique and special is that the founders of Radiolopolis implemented
      multiple educational and clinical/practical programs which have been developed
      over the past years.

PMID- 22470688
TI  - Honoring our helpers.
AB  - This special issue of the Journal of Radiology Case Reports honors the reviewers
      who donated their time and expertise throughout the year 2009 to the high quality
      and success of this journal.

PMID- 22470689
TI  - A quick look back - 2009 journal resume.
AB  - This is a quick retrospective view back to the year 2009, summarizing the
      journal's experience and demonstrating submission statistics of the Journal of
      Radiology Case Reports.

PMID- 22470690
TI  - MRI findings in herniation of the spinal cord.
AB  - Herniation of the spinal cord is a rare condition that causes non specific
      neurological deficits that are often a diagnostic challenge to clinicians.
      Despite several reports in the neurosurgical literature, it is only recently that
      the imaging appearances of this condition have come to be recognised, due mainly
      to the widespread adoption of spinal MRI. It is important for radiologists to
      recognise the telltale MRI features of this condition, as several cases have
      undergone initial misdiagnosis, resulting in delayed treatment We present a case
      with typical imaging features to familiarise radiologists with this condition, as
      it is likely that more cases will come to the fore, with more spinal MRIs being
      performed.

PMID- 22470691
TI  - Pediatric gastric teratoma.
AB  - Neoplasms from germ cell origin are a heterogeneous group of tumors rarely seen
      in the pediatric population, teratoma is the most frequent among them. They can
      occur in either gonadal or extragonadal locations. Extragonadal teratoma arising
      from abdominal viscera is very unusual. There are less than a hundred reported
      cases of gastric teratoma in the worldwide literature. Since the occurrence of
      this pathology in the pediatric age group is quite rare, we describe a case of a
      teratoma located in the lesser curvature of the stomach in an infant with an
      emphasis in radiologic-pathologic correlation.

PMID- 22470692
TI  - Sinistral portal hypertension: presentation, radiological findings, and treatment
      options - a case report.
AB  - Sinistral portal hypertension occurs when a pathological process causes occlusion
      of the splenic vein. The resultant elevated splenic bed venous pressure causes
      formation of gastric varices which can lead to hematemesis as a common
      presentation for this disease process. We present a case of sinistral portal
      hypertension in a patient with acute hematemesis as the primary presentation.
      Despite the challenging diagnosis process, the patient underwent splenectomy and
      was managed appropriately according to previously published literature.

PMID- 22470693
TI  - Gossypiboma of the breast: imaging findings.
AB  - We report a case of retained surgical sponge in the breast with its sonographic
      and magnetic resonance (MR) imaging findings. Striped and spotted low signal
      intensity structures seen within the lesion on T2 weighted MR imaging was
      characteristic. Sonographic examination also was helpful with the appearance of
      strong posterior acoustic shadowing at the lesion. It is extremely rare, to see a
      gossypiboma in the breast. A high degree of suspicion and imaging findings are
      very important for the diagnosis.

PMID- 22470694
TI  - A Tender Pulsatile Epigastric Mass is NOT Always an Abdominal Aortic Aneurysm: A
      Case Report and Review of Literature.
AB  - Of greatest concern in the assessment of a patient with a tender pulsatile
      abdominal mass is the possibility of a leaking or ruptured Abdominal Aortic
      Aneurysm (AAA). Other serious abdominal pathologies may demonstrate the same
      clinical signs but require entirely different treatments. Even amongst patients
      with proven abdominal aortic aneurysms CT imaging findings may influence the
      timing and nature of surgery and provide useful prognostic information. We
      present a case in which a large abdominal tender pulsatile mass was not aortic in
      origin. The patient had a significantly large tender congested liver associated
      with right side heart failure due to progressive tricuspid valve regurgitation.
      We have also discussed the differential diagnoses which may mimic abdominal
      aneurysms and discussed the role of imaging in resolving these problems.

PMID- 22470695
TI  - Educational treasures in Radiology: The Radiology Olympics - striving for gold in
      Radiology education.
AB  - This article focuses on Radiology Olympics (www.RadiologyOlympics.com) - a
      collaboration with the international Radiology community for Radiology education,
      Radiolopolis (www.Radiolopolis.com). The Radiology Olympics honour the movers and
      shakers in Radiology education and offer an easy to use platform for educating
      medical professionals based on Radiology cases.

PMID- 22470696
TI  - CT and MR findings in extramedullary haematopoiesis with biliary system
      encasement: a case report.
AB  - Extramedullary haematopoiesis is the production of blood elements outside the
      bone marrow cavity. In our case computed tomography and magnetic resonance
      imaging revealed the presence of a rare localization of extramedullary
      haematopoiesis with encasement of the biliary system in a 59 years-old male
      Caucasian patient, with chronic myelofibrosis and hepatic failure's
      symptomatology. Computed tomography detected the presence of homogeneous
      hypodense tissue around intra-hepatic bile ducts with minimal contrast
      enhancement, strongly suggestive for extramedullary haematopoiesis. Magnetic
      resonance confirmed the presence of a solid tissue surrounding the biliary tree,
      showing late enhancement after gadolinium administration suggestive for non
      active lesion of extramedullary haematopoiesis. Final diagnosis was established
      by percutaneous biopsy.

PMID- 22470697
TI  - Groove pancreatitis: A Case Report and Review of the Literature.
AB  - Groove pancreatitis is a rare form of segmental chronic pancreatitis. It involves
      the anatomic space between the head of the pancreas, the duodenum and the common
      bile duct. It was first described in the early 1970s, but it remains largely
      unfamiliar to most physicians. Radiological diagnosis can be challenging, as it
      is often difficult to differentiate it from other entities. The differential
      diagnosis from pancreatic head carcinoma may be difficult and recognition of
      subtle differences between these two entities is extremely important as the
      management differs significantly. Groove pancreatitis can be managed by
      conservative medical treatment, and surgery is reserved only for patients with
      persistent and severe clinical symptoms. We present a case of a 27 year-old male
      with groove pancreatitis and discuss the Magnetic Resonance Imaging (MRI)
      appearance of this entity as well as the differential diagnosis.

PMID- 22470698
TI  - Hyperostosis - an unusual radiographic presentation of Myelodysplastic Syndrome
      transformed to Acute Myeloid Leukemia.
AB  - Acute myeloid leukemia (AML) is also referred to non-lymphocytic leukemia in the
      literature. It comprises about 15% of the childhood leukemia. There are multiple
      subtypes of AML from M0-M7 with approximately 45% of the cases being M0-M2 and
      the remaining subtypes being rare. The definitive diagnosis relies on bone marrow
      biopsy showing bone marrow infiltration with leukemic cells. We describe a rare
      radiographic presentation of myelodysplastic syndrome (MDS) transformed to AML in
      an 8 month old boy who presented with a orbital wall fracture, periosteal
      reaction, and mixed lytic and sclerotic lesions.

PMID- 22470699
TI  - Hepatic endometriosis mimicking metastatic disease: a case report and review of
      the literature.
AB  - Endometriosis of the liver is an uncommon disease characterized by the presence
      of endometrial tissue in the liver. There are no pathognomonic radiological
      features for hepatic endometriosis and preoperative diagnosis is difficult by
      imaging. Most cases are diagnosed after surgery. We report atypical imaging
      features of hepatic endometriosis in a 61 year-old female that mimic metastatic
      disease to the liver. She was referred to our institution with a presumed
      diagnosis of metastatic neuroendocrine tumors to the liver. After imaging guided
      core biopsy and histologic and immunohistochemical analysis, the diagnosis of
      hepatic endometrial stromal proliferation was made. We review the literature and
      provide imaging features that may help in reaching the correct diagnosis of
      hepatic endometriosis.

PMID- 22470700
TI  - Incidentally detected unilateral pulmonary artery agenesis with pulmonary
      hypoplasia in a 67 year old woman.
AB  - Unilateral pulmonary artery agenesis is commonly seen associated with other
      congenital cardiovascular defects, when it is detected early in life, but
      isolated absence of the pulmonary artery is a rare entity, usually detected in
      adulthood. The latter patients are usually asymptomatic or might present with
      varied non-specific manifestations such as respiratory tract infections and
      hemoptysis. This report describes the imaging findings of a 67 year old female
      with absence of the right pulmonary artery. The embryology and clinical
      manifestations of the condition are reviewed.

PMID- 22470701
TI  - Spontaneous pneumomediastinum due to achalasia: an unusual but benign cause.
AB  - Pneumomediastinum is usually first identified radiographically in the emergency
      department. Distinguishing benign from more ominous causes, such as esophageal
      rupture, is imperative, particularly in the setting of associated esophageal
      disease. We describe a case, with correlative imaging, of spontaneous
      pneumomediastinum as the initial presentation of achalasia. A general discussion
      of spontaneous pneumomediastinum is also provided, including the pathophysiology,
      precipitating and predisposing factors, clinical manifestations, role of
      radiology in the diagnosis as well as the radiographic signs.

PMID- 22470702
TI  - Honoring our helpers.
AB  - This special issue of the Journal of Radiology Case Reports honors the reviewers
      who donated their time and expertise throughout the year 2010 to the high quality
      and success of this journal.

PMID- 22470703
TI  - A quick look back - 2010 journal resume.
AB  - This is a quick retrospective view back to the year 2010, summarizing the
      journal's experience and demonstrating submission statistics of the Journal of
      Radiology Case Reports.

PMID- 22470704
TI  - Giant urethral stone presenting as a scrotal mass: Case report.
AB  - Primary urethral stones are a rare form of urolithiasis accounting for less than
      0.3% of urinary stones. We are reporting a case of a giant primary urethral stone
      that developed in the penile urethra resulting from a post-surgical complication
      of urethral stricture. The patient presented with difficulty urinating,
      ejaculatory dysfunction, and a hard palpable scrotal mass.

PMID- 22470705
TI  - Vicarious urinary excretion of iodinated contrast in a Crohn's patient.
AB  - Vicarious renal excretion of iodinated contrast introduced into the bowel is a
      known phenomenon that has rarely been reported. In clinical settings like Crohn's
      disease in which evaluation for recto-vesical fistula is frequently requested,
      vicarious excretion can cause misapprehension and error in diagnosis. We present
      a case of Crohn's disease in which gastrografin enema was performed to evaluate
      for fistula and initial interpretation was mistakenly positive, however, simple
      methods of elucidation were utilized to prevent error in diagnosis.

PMID- 22470706
TI  - Sonographic features of tubo-ovarian abscess mimicking an endometrioma and review
      of cystic adnexal masses.
AB  - A 36-year-old female presented with constant, worsening left lower quadrant pain
      without associated fever or vaginal discharge. Pelvic and transvaginal ultrasound
      examinations were performed which demonstrated a large complex cystic structure
      in the left adnexa with peripheral flow on color Doppler imaging. Given the
      sonographic appearance and patient symptoms, possibilities included endometrioma
      or hemorrhagic cyst. Tubo-ovarian abscess (TOA) and other cystic ovarian masses
      were considered less likely. Two days later, the patient returned with severe
      pelvic pain as well as fever and leukocytosis. Follow-up ultrasound showed
      enlargement of the mass and a tubo-ovarian abscess (TOA) was suspected.
      Ultrasound-guided transvaginal abscess drainage was performed with removal of
      purulent fluid. The case demonstrates that the radiological features of TOA may
      mimic those of adnexal cystic masses such as an endometrioma or hemorrhagic cyst.
      A complementary case is also included which demonstrates similar sonographic
      findings in a patient with endometrioma. In addition to sonographic imaging, a
      thorough clinical and laboratory evaluation is important in differentiating these
      entities. Furthermore, we provide a comprehensive discussion about imaging
      features of cystic ovarian mass on different imaging modalities.

PMID- 22470707
TI  - Successful transcatheter arterial embolisation of a cystic artery pseudoaneurysm
      secondary to calculus cholecystitis: a case report.
AB  - Pseudoaneurysms of the cystic artery secondary to calculus cholecystitis are
      rare. In this report we describe a case of an elderly female who presented with
      abdominal pain, pyrexia, anaemia and jaundice. She had known chronic
      cholecystitis, but was not considered a suitable surgical candidate. Contrast
      enhanced computed tomography (CECT) demonstrated a probable aneurysm within the
      gallbladder fossa. The patient proceeded to digital subtraction angiography
      (DSA), which confirmed an aneurysm arising from the cystic artery and was
      subsequently managed with transcatheter arterial embolisation using coils. This
      case report reviews the diagnosis and management of this rare complication.

PMID- 22470708
TI  - Chronic pulmonary aspergillosis - longterm follow-up over 20 years, a case
      report.
AB  - We describe a case of chronic pulmonary aspergillosis complicated with a slowly
      growing aspergilloma followed for two decades without specific intervention. It
      developed with no background of local or systemic immune dysfunction in a middle
      aged female. The case illustrates many features of this disease as well as
      uniquely documenting the natural radiological evolution from a small non-specific
      cystic lesion to a massive aspergilloma. The aspergilloma subsequently autolysed
      and the patient's condition changed to an allergic phenotype with development of
      widespread bronchiectasis and pulmonary fibrosis. We briefly discuss the range of
      disease aspergillus can cause in humans, its differential diagnosis and
      treatments.

PMID- 22470710
TI  - Inside the musician's brain.

PMID- 22470709
TI  - Calcified Lymph Nodes Causing Clinically Relevant Attenuation Correction
      Artifacts on PET/CT Imaging.
AB  - There are several artifacts unique to PET/CT imaging, with CT-based attenuation
      correction (AC) artifacts being among the most commonly reported. AC artifacts
      from calcified lymph nodes represent clinically significant and easily
      misinterpreted PET/CT artifacts that have received little attention in the
      literature. In this case series, we report three cases of calcified lymph nodes
      causing an AC artifact and one case of a highly calcified lymph node without an
      AC artifact. All three cases of calcified lymph nodes causing an AC artifact
      would have resulted in a change in patient staging, and likely management, if the
      nodes had been misinterpreted as malignant nodes. In PET/CT imaging, this
      artifact needs to be considered as a potential cause of apparent FDG activity
      when calcified lymph nodes are present on the CT portion of a PET/CT study in
      order to avoid misinterpretation and potential patient mismanagement.

PMID- 22470711
TI  - JRCR - updated author guidelines.
AB  - This article describes updates on author guidelines for manuscripts submitted
      after February 1(st) 2010 to the interactive Journal of Radiology Case Reports.

PMID- 22470712
TI  - Utility of aortic cuffs in converting initially ineligible patients due to
      unfavorable neck anatomy into successful candidates for endovascular aortic
      aneurysm repair: A Case Series.
AB  - Endovascular repair of the abdominal aortic aneurysm has been established as a
      successful alternative to open surgical repair, provided that the criteria
      necessary for such an approach are fulfilled. Anatomic criteria include suitable
      diameter, length, and angle of the aneurysm proximal neck. We present three cases
      in which patients were initially ineligible for endovascular repair because of
      unfavorable neck anatomy but in whom the use of aortic cuffs allowed for
      successful endograft placement and aneurysm exclusion.

PMID- 22470713
TI  - Opposite cerebral dominance for reading and sign language.
AB  - We present a case of right hemispheric dominance for sign language but left
      hemispheric dominance for reading, in a left-handed deaf patient with epilepsy
      and left mesial temporal sclerosis. Atypical language laterality for ASL was
      determined by preoperative fMRI, and congruent with ASL modified WADA testing. We
      conclude that reading and sign language can have crossed dominance and
      preoperative fMRI evaluation of deaf patients should include both reading and
      sign language evaluations.

PMID- 22470714
TI  - Ileal atresia with meconium peritonitis: fetal MRI evaluation.
AB  - We report a case of ileal atresia with meconium peritonitis evaluated by fetal
      MRI. Prenatal ultrasounds in the third trimester initially demonstrated a cystic
      abdominal mass that resolved with development of dilated bowel loops. Fetal MRI
      at 32 weeks gestation identified a perihepatic collection with several dilated
      small bowel loops and normal sized meconium filled rectosigmoid consistent with
      distal bowel perforation and loculated meconium peritonitis. Following delivery,
      the infant presented with bowel obstruction. Contrast enema revealed a normal
      sized rectosigmoid with small ascending and transverse colon. A distal ileal
      atresia type IIIa was documented at surgery.

PMID- 22470715
TI  - Gardner syndrome complicated with hydronephrosis. A case report.
AB  - Gardner syndrome is an autosomal dominant disease characterized by the presence
      of colonic polyposis, osteomas and soft tissue tumors. We present a case of a man
      who was admitted for a relapse of adenocarcinoma of the rectum. CT-staging showed
      multiple locations of desmoid tumors and osteomas, with final diagnosis of
      Gardner syndrome. The follow-up CT, after surgery and chemotherapy, showed a
      relapse of the lesions with hydronephrosis due to ureteral compression.

PMID- 22470716
TI  - CT Utilization in the Prospective Diagnosis of a Case of Swine-Origin Influenza A
      (H1N1) Viral Infection.
AB  - The purpose of this paper is to demonstrate the potential role of CT in the early
      diagnosis of swine-origin influenza A (H1N1) virus (S-OIV) pneumonia. We present
      a case of acute influenza-like illness in which the CT findings of
      peribronchovascular and subpleural ground-glass opacities and consolidation
      resembled organizing pneumonia, and lead the radiologist to prospectively and
      correctly suggest the diagnosis of S-OIV infection.

PMID- 22470717
TI  - FDG uptake in sternoclavicular joint synovitis: mimic of internal mammary
      adenopathy.
AB  - False-positive FDG uptake has been noted in a wide range of benign processes. In
      this report, we describe a case of FDG uptake in unilateral sternoclavicular
      synovitis which mimicked an internal mammary node in appearance. Knowledge of
      this potential false-positive is particularly important in breast cancer patients
      with a propensity of internal mammary nodal metastases.

PMID- 22470718
TI  - Case report: gastric adenocarcinoma metastatic to the prostate gland.
AB  - Metastasis to the prostate gland from gastric cancer is exceedingly rare. We have
      presented a rare case of gastric malignancy metastasizing to the prostate
      diagnosed by transrectal ultrasound guided prostate biopsy.

PMID- 22470720
TI  - Cleidocranial dysplasia (CCD) causing respiratory distress syndrome in a newborn
      infant. A case report.
AB  - Cleidocranial dysplasia (CCD), also known as Scheuthauer Marie-Sainton Syndrome,
      is a rare autosomal dominant inherited disorder, characterized by general
      retardation in bone ossification, hypoplastic clavicles and various craniofacial
      and dental abnormalities. Early diagnosis of CCD can be difficult, because the
      majority of craniofacial abnormalities become obvious only during adolescence. We
      present a rare case of CCD with neonatal manifestation and would like to promote
      the awareness of this rare disorder and the importance of early diagnosis.

PMID- 22470719
TI  - Coronary arteriovenous malformation, as imaged with cardiac computed tomography
      angiography: A case series.
AB  - INTRODUCTION: Coronary Arteriovenous Malformations (AVM) can lead to various
      cardiovascular events. The severity of clinical manifestation depends on the
      degree of the malformation. The significance of major arterial shunt is that they
      can deprive the myocardium of the necessary amount of blood, leading to
      myocardial ischemia, and potentially tachycardia, left ventricular dilatation and
      heart failure secondary to increased stroke volume and cardiac output. Cardiac
      computed tomography (CCT) has proven to be a good non-invasive diagnostic tool in
      the detection of coronary Arteriovenous Malformations. CASE PRESENTATION: We
      include 4 patients, who presented with various symptoms in relation to the
      coronary Arteriovenous Malformations. Diagnostic confirmation was made non
      invasively using multi-row detector cardiac computed tomography (MDCT).
      CONCLUSION: Coronary Arteriovenous Malformation is a rare congenital disease
      which can produce symptoms of varying severity depending on the size of the
      malformation. CCT angiography can help in non-invasively diagnosing the
      malformation along with revealing the anatomic details, which can be used for
      surgical planning, or for better medical management of the patients.

PMID- 22470721
TI  - Fasciola hepatica infection in a 65-year-old woman.
AB  - Fascioliasis is an infectious disease caused by fasciola or liver fluke. Humans
      are accidental hosts to these flatworms. The World Health Organisation considers
      fascioliasis an important human parasitic disease. In Europe, Australia and
      Northern America, the disease is rare, but should have a high index of suspicion
      in patients who have lived in or travelled to endemic areas. Although it can be
      self-limiting, fascioliasis is associated with an increased risk of bile duct
      cancer. Before a clear-cut diagnosis is made using ELISA-based arrays, radiologic
      studies can provide the clinician with a number of suggestive features, thereby
      avoiding the need for liver biopsy or even surgery, which have nowadays become
      obsolete for the diagnosis of fascioliasis. We provide an overview of the major
      radiologic hallmarks and we demonstrate the role of iron-oxide enhanced MRI.

PMID- 22470722
TI  - Stent-assisted coil embolization of a wide-necked renal artery aneurysm.
AB  - We present a case of stent-assisted coil embolization of a wide-necked renal
      artery aneurysm performed at our institution. The technique involved a stent
      being delivered over the neck of the aneurysm. Subsequently a catheter was placed
      into the aneurysm through the stent mesh and the aneurysm was then filled with
      detachable coils. Complete aneurysm occlusion was obtained and there was no
      evidence to suggest renal infarction on a follow-up contrast CT scan 6 months
      later. Our preliminary experience suggests that stent-assisted coil embolization
      of wide-necked renal artery aneurysms is a technically challenging but
      potentially effective renal-sparing endovascular approach.

PMID- 22470723
TI  - Spontaneous pneumomediastinum associated with sex.
AB  - We present a case of spontaneous pneumomediastinum (SPM) associated with sex. A
      22-year-old lesbian with a history of asthma, cigarette and illicit drug smoking
      was diagnosed with a SPM after developing chest pain and dyspnoea in the context
      of performing oral sex. The main finding was subcutaneous emphysema involving the
      neck. SPM is an important differential diagnosis for chest pain in young people.
      It is a benign condition and diagnosis mainly limited to chest X-ray with
      increased incidence in asthmatics, smokers and drug addicts.

PMID- 22470724
TI  - Spontaneous celiac artery dissection and its management.
AB  - Spontaneous visceral artery dissection is an uncommon event with an unpredictable
      natural history with superior mesenteric artery being the most common affected
      artery. It is most often asymptomatic and usually diagnosed at autopsy. Pre
      disposing factors are not specific but have been suggested to be pre-existing
      vascular disease, hypertension and pregnancy. Spontaneous resolution, definitive
      occlusion of the artery, and formation of an aneurysm with associated
      complications are some other possible outcomes. Isolated dissection of the celiac
      artery (CA) is rare and there are only a few cases reported in the literature. We
      present a case of a 65 year old male with spontaneous celiac artery dissection
      and provide a review of the current literature about imaging findings and
      management of this entity.

PMID- 22470725
TI  - FDG PET/CT diagnosis of hepatic lymphoma mimicking focal fatty infiltration on
      CT.
AB  - Areas of hypoattenuation in the liver which do not have mass effect are typically
      thought to represent focal fatty infiltration. Rarely, tumors can present without
      mass effect in the liver. We present a case in which areas of liver
      hypoattenuation which were initially thought to represent focal fatty
      infiltration on CT due to lack of mass effect had abnormal uptake on a FDG PET/CT
      exam; these areas were due to secondary hepatic involvement from non-Hodgkin's
      lymphoma.

PMID- 22470726
TI  - Educational treasures in Radiology: A highly customizable Radiology specific
      literature search engine.
AB  - This article focuses on PubRad (www.pubrad.org) - a custom defined and Radiology
      targeted medical literature search software which can be used in multiple ways to
      adjust to the individual user's needs. PubRad can be used from its website, from
      the user's desktop, it can be implemented into the user's own website or can be
      even integrated into third party programs.

PMID- 22470727
TI  - Vascular anomaly at the craniocervical junction presenting with sub arachnoid
      hemorrhage: Dilemma in Imaging Diagnosis, Endovascular Management and
      Complications.
AB  - We present a case of a ruptured vertebral artery dissecting aneurysm that
      mimicked a presumed vascular anomaly by CTA (Computerized Tomographic
      Angiography). A parenchymal arteriovenous malformation (AVM) or a dural
      arteriovenous fistula (DAVF) at the craniocervical junction can present with a
      subarachnoid hemorrhage and cannot be differentiated from a vertebral artery
      dissection by non invasive imaging. Catheter based cerebral angiography revealed
      a dissecting pseudoaneurysm of a diminutive right vertebral artery terminating in
      the posterior inferior cerebellar artery (PICA) that to our knowledge has not
      been previously reported. NBCA (N-Butyl Cyanoacrylate) embolization of the
      pseudoaneurysm lumen and sacrifice of the parent vessel resulted in cerebellar
      infarction, requiring an emergent decompressive craniectomy. The patient
      recovered to a functional neurologic status.

PMID- 22470728
TI  - A novel plain abdominal radiograph sign to diagnose malrotation with volvulus.
AB  - Malrotation with associated volvulus is a potentially lethal event for a neonate.
      The gold standard for diagnosis is an upper gastrointestinal contrast study.
      However this can delay the diagnosis and the timing of surgical intervention. We
      present a novel abdominal radiographic sign; duodenal and gastric dilatation
      occurring in association with limited small bowel gas confined to the right lower
      quadrant of abdomen and the total absence of colonic air that is indicative of
      malrotation with associated volvulus. This allows for an earlier diagnosis and
      expeditious surgery.

PMID- 22470729
TI  - Spondyloarthritis: a gouty display.
AB  - Gout is a systemic, metabolic disease that typically affects the peripheral
      joints. We describe an unusual presentation of gout affecting the facet joints
      and costovertebral joints in the thoracic and lumbar spine. A 54-year old man
      presents to the emergency department with increasing swelling and pain at the
      left elbow for one week and difficulty ambulating. The imaging work-up included
      plain radiographs of the left elbow, left wrist, and chest with subsequent
      admission for possible septic arthritis. MRI of the elbow showed olecranon
      bursitis and an erosion of the lateral epicondyle. CT scan demonstrated lytic
      cloud-like lesions localized to the facet joints and costovertebral joints of the
      thoracic and lumbar spine as well as bilateral medullary nephrocalcinosis.
      Possible hyperparathyroidism manifestations (including Brown tumors and medullary
      nephrocalcinosis) were evaluated with plains films of the hands; x-rays instead
      showed classic gouty arthritis. Our report reviews the disease, epidemiology,
      classic radiologic findings, and treatment of gout.

PMID- 22470730
TI  - Metastatic Breast Cancer to the Bladder case report and review of literature.
AB  - The main cause of mortality among patients with breast cancer is the metastatic
      spread of the primary tumour. The urinary bladder is considered as an unusual
      site for breast cancer metastasis. A patient has presented with right breast
      tumour and qualified for surgical treatment. After removal of the mass, an intra
      operative and final pathology evaluation indicated breast invasive lobular
      carcinoma. Adjuvant chemotherapy was given. Years later, an increase of serum
      CA15-3 tumour marker level was noted and physical examination revealed a lump at
      the mastectomy scar. A follow-up abdominal ultrasound scan demonstrated
      thickening of the urinary bladder wall segment, confirmed later by CT scan. A
      transurethral resection of bladder was performed, reaffirming a neoplastic mass,
      with histological assessment revealing invasive breast carcinoma. Palliative
      chemotherapy was given and another follow-up ultrasound scans were unremarkable.
      The patient is alive today.

PMID- 22470731
TI  - Blunt abdominal trauma - An important cause of portal venous pseuodoaneurysm.
AB  - Aneurysms and pseudoaneurysms of the portal venous system are rarely seen
      following abdominal trauma but clinicians need to be aware of them as possible
      vascular complications following blunt trauma. This case report of a 10 year old
      boy following a handlebar injury demonstrates a clear causal relationship between
      trauma and portal venous pseudoaneurysm. Portal venous aneurysms have a
      prevalence of less than 0.4% and most are found in patients with underlying
      hepatocellular disease. Many are asymptomatic in which case surveillance is an
      accepted management strategy, with Doppler ultrasound proving useful.
      Complications including thrombosis, distal embolism, compression of the biliary
      tree and haemorrhage are usually indications for surgical management. Portal
      venous pseudoaneurysms may be managed conservatively but transcatheter
      embolisation can be used if there are ongoing complications or haemorrhage.

PMID- 22470733
TI  - Percutaneous transrenal retrieval of fractured nephrostomy tube under
      fluoroscopic guidance.
AB  - Percutaneous nephrostomy is a safe procedure, performed routinely by
      interventional radiologists, and has a low complication rate. We report an
      unusual case of a fractured nephrostomy tube, retained within the kidney, having
      its fractured end trapped within the healed retroperitoneal tract. The catheter
      was retrieved by snaring it, using a percutaneous access to the collecting
      system. We describe the technique used and the alternative management options.

PMID- 22470732
TI  - Expectant and medical management of placenta increta in a primiparous woman
      presenting with postpartum haemorrhage: The role of Imaging.
AB  - We report a case of postpartum hemorrhage due to adherent placenta. A 28 year old
      primiparous woman who underwent manual removal of placenta for primary postpartum
      haemorrhage soon after delivery was referred to our Institute on her third
      postnatal day because of persistent tachycardia and low grade fever. Placenta
      accreta was suspected on initial ultrasonographic examination. MRI examination
      confirmed the diagnosis of placenta accreta in few areas and revealed increta in
      other areas. On expectant management she developed genital tract sepsis and hence
      she was treated with intravenous Methotrexate after controlling infection with
      appropriate antibiotics. Doppler Imaging showed decreased blood flow to the
      placental mass and increased echogenecity on gray scale USG after Methotrexate
      administration. She expelled the whole placental mass on 35th postnatal day and
      MRI performed the next day showed empty uterine cavity. Morbid adhesion of
      placenta should be suspected even in primiparous women without any risk factors
      when there is history of post-partum hemorrhage. MRI is the best modality for
      evaluation of adherent placenta.

PMID- 22470734
TI  - Osteoblastoma of the frontal sinuses presenting with headache and blurred vision:
      case report and review of the literature.
AB  - Osteoblastoma is a rare benign bone tumor that usually arises in the vertebral
      column and long bones of young adults. Craniofacial involvement is extremely
      rare. To date, osteoblastoma of the frontal sinus has not been reported in the
      English literature. We report an osteoblastoma of both frontal sinuses in a 23
      year-old male who presented with headache and blurry vision in the left eye.
      Computed tomography (CT) demonstrated an expansile lesion involving both frontal
      sinuses with sclerotic and fibrous components, eroding into the roof of the left
      orbit. On magnetic resonance imaging (MRI) the dense portion of the lesion showed
      signal void on all sequences, while the fibrous matrix was isointense to grey
      matter on T1-weighted and T2-weighted images and showed avid enhancement
      following intravenous contrast administration. Surgical resection was performed
      and histology was consistent with osteoblastoma.

PMID- 22470735
TI  - Congenital esophageal stenosis: a rare case of dysphagia.
AB  - Congenital esophageal stenosis (CES) is a rare anomaly, resulting from incomplete
      separation of the respiratory tract from the primitive foregut at the 25th day of
      life. First clinical signs are abnormalities of the swallowing mechanism caused
      by the intrinsic narrowing of the esophagus. Diagnosis is usually delayed,
      requiring an accurate history and high level of suspicion, alongside with an
      esophagogram. Definite diagnosis is only confirmed by histological examination.
      Treatment usually involves surgery, depending on the severity, location and type
      of stenosis. We report the case of an 18 months old toddler diagnosed with CES.
      The characteristic radiographic and CT features are presented as well as the
      histology.

PMID- 22470736
TI  - Spinal gout mimicking paraspinal abscess: A case report.
AB  - Gout is usually thought of as a peripheral joint disease. However, case reports
      are available describing gouty lesions in the spine. We report a case of a 51
      year old African American woman with no previous history of gout who presented
      with lower back pain and fever and was found to have multiple small fluid
      collections in the paraspinal muscles at the L3 to L5 levels on the MRI. She was
      empirically treated with antibiotics, since the fluid was not accessible for
      drainage initially. Unsuccessful antibiotic therapy and an episode of peripheral
      gout during this hospitalization prompted the diagnosis of axial gout as the
      cause for the paraspinal lesions in this patient. CT guided aspiration of the
      paraspinal lesions confirmed monosodium urate (gout) crystals under polarized
      microscopy.

PMID- 22470737
TI  - Giant aneurysm formation in sporadic renal angiomyolipoma.
AB  - Angiomyolipomas are the most common mesenchymal renal neoplasms. Two types have
      been described: (i) sporadic angiomyolipoma and (ii) angiomyolipoma associated
      with tuberous sclerosis. Giant aneurysm formation is usually noted in
      angiomyolipomas associated with tuberous sclerosis and is rare in sporadic
      variety. Tumor diameter and aneurysm diameter have been used as predictors of
      rupture. We report a rare case of aneurysm formation in a sporadic
      angiomyolipoma.

PMID- 22470739
TI  - Monro unveiled.

PMID- 22470738
TI  - Portal vein aneurysms: a case series with literature review.
AB  - Portal vein aneurysms are a relatively uncommon entity and often an incidental,
      asymptomatic finding. Recognition of this finding can help to avoid potential
      confusion with abdominal masses of other etiologies. We would like to present
      four cases of portal vein aneurysms, and discuss the natural history, imaging
      findings, and treatment of this condition. One of the cases of portal vein
      aneurysm presented occurred after liver transplantation, which, to the best of
      our knowledge, has only been described once in the English-language literature.

PMID- 22470740
TI  - Combined percutaneous and endoscopic approach in management of dropped gallstones
      following laparoscopic cholecystectomy.
AB  - Dropped gallstones due to accidental perforation of gallbladder wall during
      laparoscopic cholecystectomy are often encountered. However, dropped gallstones
      as nidus of infection with subsequent abscess formation is a rare complication of
      laparoscopic cholecystectomy (0.3%). Most of the reported cases of complicated
      dropped stones required open surgical drainage. Minimally invasive measures were
      less frequently employed. We report a case of dropped gallstones that were
      removed endoscopically through a percutaneous drainage tract.

PMID- 22470741
TI  - Imaging Keratitis-Icthyosis-Deafness (KID) syndrome with FDG-PET (F18
      fluorodeoxiglucose-Positron Emission Tomography).
AB  - Keratitis-Icthyosis-Deafness (KID) syndrome is a rare dysplasia characterized by
      vascularizing keratitis, congenital sensorineural hearing-loss, and progressive
      erythrokeratoderma. To our knowledge, this is the first KID syndrome imaged with
      FDG-PET in the literature. This paper is intended to help familiarize with the
      FDG abnormalities related to this rare entity.

PMID- 22470742
TI  - Renal neuroectodermal tumour presenting with hematuria.
AB  - Peripheral primary neuroectodermal tumors (PNET) are uncommon tumors, with an
      overall incidence of 1% of all sarcomas. Renal PNET is extremely rare. It is an
      aggressive tumor, with a high incidence of local recurrence and early metastases.
      Radiological diagnosis can be challenging as it is often difficult to
      differentiate it from other primary renal neoplasms. Imaging features include a
      large heterogeneous mass with central low density areas due to necrosis. Intra
      tumor hemorrhage and calcification are rare. We present a rare case of a large
      PNET mimicking renal cell carcinoma in a 51 year old female that required
      arterial embolization and nephrectomy.

PMID- 22470743
TI  - Solitary fibrous tumor originating in the pelvis: a case report.
AB  - A 52 year old male presented with changes in bowel movements, and a mass was
      detected on digital rectal exam. Both CT and MRI revealed a large pelvic and
      gluteal mass filling the pelvic cavity displacing the adjacent pelvic structures.
      After surgical removal, pathology revealed solitary fibrous tumor; a rare
      neoplasm uncommonly discovered in the thorax, and even less commonly in
      extrapleural locations. We discuss in this article imaging findings and
      histological features of extrapleural solitary fibrous tumor.

PMID- 22470744
TI  - Pseudocoarctation with saccular aneurysms, left sided SVC and aberrant right
      subclavian artery - A case report.
AB  - Pseudocoarctaion is a rare congenital anomaly due to elongation of aortic arch.
      The exact etiology is still uncertain. It may be associated with other congenital
      cardiac and vascular anomalies. We report an unusual case of pseudocarctation
      associated with aberrant right subclavian artery, left SVC and multiple saccular
      aneurysms in the kinked arch and we feel that this is the first documented case
      in literature.

PMID- 22470745
TI  - Gynaecomastia associated with highly active antiretroviral therapy (HAART).
AB  - There is a global Acquired Immune Deficiency Syndrome (AIDS) epidemic. It is
      estimated that the total number of people living with Human Immune deficiency
      Virus (HIV) is 33.2 million in the year 2007. An estimated 2.1 million people
      died from AIDS in 2007. As highly active antiretroviral therapy (HAART) becomes
      more widely used, the side effects of this regime are becoming more evident in
      clinical practice. We present 2 cases that demonstrate the association of HAART
      and gynaecomastia. Imaging features of gynaecomastia and the differential for
      these changes will be reviewed. Proposed mechanisms for the pathogenesis of
      gynaecomastia will be discussed. Possible therapeutic options will also be
      briefly considered.

PMID- 22470746
TI  - Coexisting MS and Lhermitte-Duclos Disease.
AB  - We report the case of a patient with pre-existing multiple sclerosis, who
      presented with horizontal diplopia, and a prior episode of progressive ataxia and
      dizziness lasting one week. While initially attributed to multiple sclerosis,
      subsequent imaging demonstrated a concurrent left cerebellar gangliocytoma, also
      known as Lhermitte-Duclos disease.

PMID- 22470747
TI  - Primary synovial osteochondromatosis of the surapatellar pouch of knee.
      Correlation of imaging features with surgical findings.
AB  - A 31 years old female presented with swelling and pain above the right knee for
      three years. On examination, there was a tender swelling over the right knee more
      pronounced over the suprapatellar region. Plain X-ray, US, CT scan and MRI of the
      knee were suggestive of Primary synovial osteochondromatosis (PSC) of the
      suprapatellar pouch. Patient underwent total synovectomy and the diagnosis of
      synovial osteochondromatosis was confirmed histopathologically. Recognizing the
      imaging appearances of PSC is important to improve patient management.

PMID- 22470748
TI  - MRI findings in chronic lithium nephropathy: a case report.
AB  - Patients on long term lithium therapy for affective disorders may develop renal
      toxicity. It may manifest as nephrogenic diabetes insipidus with renal biopsy
      showing interstitial fibrosis, sclerotic glomeruli and cyst formation. Magnetic
      resonance imaging demonstrates the presence of microcysts in patients on long
      term lithium therapy, suggesting a possible cause for their nephrotoxicity. We
      describe the typical magnetic resonance imaging appearance of renal microcysts in
      a 53 year old woman on chronic lithium therapy.

PMID- 22470749
TI  - Extramedullary duodenal plasmacytoma presenting with gastric outlet obstruction
      and painless jaundice.
AB  - Malignant plasma cells in multiple myeloma are predominantly confined to the
      medullary space of the skeletal system, therefore the disease course will be
      dominated by signs and symptoms related to bone marrow infiltration and
      destructive bone lesions with their consequences as well as abnormal protein
      production. Visceral extramedullary plasmacytoma involving the gastrointestinal
      system and particularly the duodenum is a rare manifestation of the disease. We
      report a case of duodenal extramedullary plasmacytoma presenting with gastric
      outlet obstruction and painless jaundice, in a patient treated for multiple
      myeloma. Diagnosis was first suggested on imaging, and proved by endoscopic
      biopsy. The duodenal mass resolved following chemotherapy.

PMID- 22470750
TI  - Endobronchial granular cell tumor: a case report.
AB  - Granular cell tumors (GCTs) are benign neoplasms that are most commonly found in
      the head and neck region. We present a case of endobronchial granular cell tumor
      presenting as hemoptysis in a 22-year-old African American female. Patient
      subsequently underwent a right upper and middle lobectomy, and upon histologic
      analysis was found to have GCT with borders impinging upon cartilage and adjacent
      peribronchial lymph nodes.

PMID- 22470751
TI  - Mammary duct ectasia in a man with liver disease, end stage renal failure, and
      adjacent arteriovenous fistula.
AB  - Mammary duct ectasia is a rare finding in males. We report a case of mammary duct
      ectasia in a 58 year old male with liver failure and end stage renal failure. We
      discuss radiology findings of mammary duct ectasia as well as potential risk
      factors and management options for symptomatic male mammary duct ectasia.

PMID- 22470752
TI  - A case of craniofacial polyostotic fibrous dysplasia.
AB  - We present the case of a patient with craniofacial polyostotic fibrous dysplasia.
      Polyostotic fibrous dysplasia is relatively rare and usually presents in late
      childhood/early adulthood. It is occasionally associated with endocrine disorders
      such as McCune-Albright syndrome. The benign pathology of this bone tumor belies
      its implications in the region of the skull base. Craniofacial polyostotic
      fibrous dysplasia can have devastating complications depending on which ostia are
      involved, including vision loss. Our patient was already beginning to experience
      visual field deficits from ischemic neuropathy. He was treated surgically with
      optic nerve decompression; however, the efficacy of this approach is currently
      being debated.

PMID- 22470753
TI  - Metallosis and Metal-Induced Synovitis Following Total Knee Arthroplasty: Review
      of Radiographic and CT Findings.
AB  - Metallosis and metal-induced synovitis are well-recognized complications of metal
      backed polyethylene joint prostheses and have been frequently described in the
      orthopedic surgery literature; however, relatively fewer articles discussing the
      radiologic aspects of this complication have been published. To illustrate the
      importance of radiologic findings in the diagnosis and management of these
      patients, we present a case of metallosis and metal-induced synovitis
      complicating two revisions of a total knee arthroplasty, caused by polyethylene
      liner wear and dissociation of the polyethylene liner from the metal-backed
      patellar prosthesis. Specific attention is given to reviewing signs that aid in
      diagnosis, such as the "bubble sign," "cloud sign," and "metal-line signs."

PMID- 22470754
TI  - Case report of a testicular epidermoid cyst and review of its typical sonographic
      features.
AB  - A case of testicular epidermoid cyst, demonstrating multiple characteristic
      sonographic patterns in a single lesion, is presented with a brief review of the
      distinctive ultrasound features. It is important to remember that the sonographic
      patterns describing testicular epidermoids represent the varied amounts and
      arrangements of keratin of a particular lesion. A given lesion may demonstrate
      subtle variability or more than one characteristic pattern at any given time.
      With this in mind, preoperative characterization of testicular epidermoids should
      allow for increasing utilization of testicular sparring surgery in the management
      of this benign lesion.

PMID- 22470755
TI  - Acute mesenteric ischaemia on unenhanced computer-tomography.
AB  - We present a 39-year old man with mesenteric ischaemia. The initial unenhanced
      images of the, non-oral contrast CT abdomen clearly demonstrated increased
      density in a significant length of the small bowel and in the veins of the
      adjacent mesentery. Mesenteric ischaemia is a difficult diagnosis both clinically
      and radiologically and we demonstrate the potential benefits of an unenhanced
      abdominal scan (often left out if a contrast enhanced scan is to be performed)
      and the omission of oral bowel contrast in emergency scans.

PMID- 22470756
TI  - Transmural coil extrusion after embolization for colonic hemorrhage.
AB  - Transcatheter embolization is increasingly accepted as a safe and effective
      therapy for acute lower gastrointestinal hemorrhage, but the fate of the coils
      used for treatment is not entirely known. We report a patient with massive
      descending colonic bleeding, successfully treated with microcoil occlusion, in
      whom partially extruded coils were later visualized colonoscopically, but
      initially misidentified as ingested jewelry. The incidence of this endoscopically
      enigmatic (but in this case clinically inconsequential) finding is unknown.

PMID- 22470757
TI  - Pulmonary schistosomiasis - imaging features.
AB  - Schistosomiasis is a helminthic infection that is endemic in tropical and
      subtropical regions. Pulmonary involvement can be divided into two categories:
      acute or chronic compromise. Chronic and recurrent infection develops in persons
      living or travelling in endemic areas. In the lungs, granuloma formation and
      fibrosis around the schistosome eggs retained in the pulmonary vasculature may
      result in obliterative arteriolitis and pulmonary hypertension leading to cor
      pulmonale. Acute schistosomiasis is associated with primary exposure and is
      commonly seen in nonimmune travelers. The common CT findings in acute pulmonary
      schistosomiasis are small pulmonary nodules ranging from 2 to 15 mm and larger
      nodules with ground glass-opacity halo. Katayama fever is a severe clinical
      manifestation of acute involvement. We present a case of pulmonary involvement in
      schistosomiasis and provide a discussion about typical imaging findings in the
      acute and chronic form.

PMID- 22470758
TI  - Uterus didelphys with unilateral distal vaginal agenesis and ipsilateral renal
      agenesis: common presentation of an unusual variation.
AB  - Mullerian duct abnormalities are congenital malformations that are easily missed
      and can lead to incorrect diagnosis and unnecessary operative procedures. In this
      case, a young female presented with cyclic pelvic pain that continued after
      previous surgical resection of an ovarian cyst. Further investigation with
      clinical examinations and multimodality imaging demonstrated ipsilateral renal
      agenesis and a Class III Mullerian duct anomaly (MDA) requiring a second
      operative procedure. It is believed that this case is a variant of the described
      obstructed hemi-vagina with ipsilateral renal agenesis (OVIRA) anomaly as
      pathologically there was ipsilateral renal agenesis and complete vaginal agenesis
      in our case. It is imperative to have a high clinical suspicion of mullerian duct
      abnormalities when encountering a patient with other urogenital anomalies. This
      will decrease the amount of misdiagnoses, guide appropriate surgical
      intervention, and decrease the risk of future reproductive complications.

PMID- 22470759
TI  - Malignant transformation of an endometriotic cyst: MDCT and MR findings.
AB  - Malignant transformation is a rare complication of endometriosis. MR criteria for
      diagnosis include the presence of soft-tissue components, enhancement after
      contrast material administration in an endometriotic cyst. We present the
      multidetector CT and MR imaging findings in a case of an incidentally found
      endometrioid adenocarcinoma in a left-sided ovarian endometrioma, occurring in a
      30-year old woman. MR imaging enabled the correct preoperative characterization
      of the lesion, by depicting a soft-tissue element, with strong and early
      enhancement after gadolinium administration. The same area had high signal
      intensity on diffusion-weighted images and low apparent diffusion coefficient
      values due to restricted diffusion, findings also strongly suggestive of
      malignancy.

PMID- 22470760
TI  - Co-existing sarcoidosis confounds the staging of bilateral renal cell carcinoma.
AB  - We present a case in which the undiagnosed condition of sarcoidosis complicated
      the staging of bilateral, subtype-discordant renal cell carcinoma. Initially
      thought to have metastatic renal cell carcinoma based on computed tomography
      imaging and referred for immunotherapy, a positron emission tomography/computed
      tomography scan demonstrated different levels of radiotracer activity in the
      primary site and the presumed pulmonary metastatic sites. The patient underwent
      bilateral partial nephrectomies and was ultimately diagnosed with stage T1
      bilateral renal cell carcinoma and sarcoidosis. This case highlights the need to
      consider concurrent medical conditions that can lead to false positive results
      when evaluating for metastatic disease with imaging studies as well as the
      importance of evaluating the levels of radiotracer activity between different
      sites.

PMID- 22470761
TI  - Party under the sea.

PMID- 22470763
TI  - An unusual cause of external snapping hip.
AB  - The external snapping hip syndrome is a condition characterized by palpable or
      audible snap on the lateral region of the hip occurring during movements and
      sometimes associated with pain. It is typical of young adults and athletes and
      can be favored by the abnormal sliding of the iliotibial band or of the gluteus
      maximus muscle over the greater trochanter. We present a case of external
      snapping hip syndrome occurring in a young woman secondary to a dysmorphic sickle
      shaped myotendinous junction of the gluteus maximus muscle. Diagnosis was allowed
      by an integrated clinical and radiological approach, based on dynamic ultrasound
      and magnetic resonance imaging (MRI).

PMID- 22470764
TI  - Aggressive hemangioma of the thoracic spine.
AB  - Vertebral hemangiomas are common lesions and usually considered benign. A rare
      subset of them, however, are characterized by extra-osseous extension, bone
      expansion, disturbance of blood flow, and occasionally compression fractures and
      thereby referred to as aggressive hemangiomas. We present a case of a 67-year-old
      woman with progressive paraplegia and an infiltrative mass of T4 vertebra causing
      mass effect on the spinal cord. Multiple conventional imaging modalities were
      utilized to suggest the diagnosis of aggressive hemangioma. Final pathologic
      diagnosis after decompressive surgery confirmed the diagnosis of an osseous
      hemangioma.

PMID- 22470765
TI  - Investigation of polymethylmethacrylate pulmonary embolus in a patient ten years
      following vertebroplasty.
AB  - Percutaneous vertebroplasty (PV) is a procedure commonly used for the treatment
      of vertebral compression fractures, and the number of procedures has been
      steadily increasing over the past decade. We report a case of an 81 year old
      female with a history of breast cancer that developed two vertebral body
      compression fractures and was subsequently treated with PV. The patient developed
      a subsegmental pulmonary polymethylmethacrylate (PMMA) embolus as a complication
      of the procedure. Ten years following the procedure, she remained asymptomatic
      with the PMMA embolus being discovered incidentally during workup for a suspected
      chronic obstructive pulmonary disease (COPD) exacerbation. In reviewing the case,
      we describe the typical presentation of a pulmonary PMMA embolus and consider
      methods to decrease the incidence of this complication.

PMID- 22470766
TI  - A case of type A aortic dissection with underlying fibromuscular dysplasia.
AB  - Fibromuscular dysplasia is a rare, non-atherosclerotic non-inflammatory vascular
      disease that most commonly involves the renal arteries and carotid arteries, but
      has been described in nearly every vascular bed in the body. Complications of
      fibromuscular dysplasia include aneurysms and vascular dissection. We present a
      rare case of fibromuscular dysplasia involving the aorta, complicated by type A
      aortic dissection.

PMID- 22470767
TI  - Diagnostic dilemma in a neglected case of fetus-in-fetu solved with Magnetic
      Resonance Imaging and MDCT--a case report and review of literature.
AB  - Fetus-in-fetu (FIF) is a rare anomaly in which a vertebrate fetus is enclosed
      within the body of its twin in diamniotic monochorionic pregnancy. To the best of
      our knowledge, fewer than 100 cases have been reported in literature. Although a
      wide variety of presentations have been described in clinical reports, the
      characteristic features on MRI which distinguish FIF from teratoma have not been
      well delineated. Here we present a case of fetus-in-fetu in which characteristic
      MDCT and MR findings were used to diagnose FIF preoperatively and successfully
      differentiate it from teratoma. Although both CT and MRI can be used for
      definitive preoperative diagnosis of FIF, MRI is an ideal imaging modality due to
      inherent high tissue contrast and spatial resolution. Furthermore, MRI obviates
      the need for iodine contrast and eliminates the risk of ionizing radiation. We
      emphasize that MRI is an ideal valuable diagnostic tool for definite preoperative
      diagnosis of FIF and surgical planning.

PMID- 22470768
TI  - Rare combination of frontonasal and bilateral naso-orbital encephaloceles.
AB  - Encephaloceles, while a common entity affecting 1:4000 live births, typically
      occur in the occipital region. Encephaloceles involving the frontal region
      comprise only 15% of all cases. Naso-orbital encephaloceles are rarely seen. Our
      case profiles a child born at term with an atrial septal defect (ASD),
      micrognathia, cleft lip, and frontonasal as well as bilateral naso-orbital
      encephaloceles. At birth the encephaloceles were undetected. During the cleft
      palate pre-operative preparation, the bilateral naso-orbital encephaloceles were
      diagnosed as dacrocystoceles for which the child underwent surgical repair.
      Misdiagnosis and loss to follow up lead to delayed surgical treatment until the
      child was almost two years of age; the right eye was near complete closure due to
      the increasing size of the encephalocele. This case highlights the importance of
      meticulous radiologic interpretation of midline nasal masses, as a correct
      diagnosis impacts clinical management and directs surgical repair.

PMID- 22470769
TI  - Intraosseous schwannoma of the petrous apex.
AB  - Primary neoplasms of the petrous apex are rare and include eosinophilic
      granuloma, chondroma, chondrosarcoma, chordoma, and schwannoma. We report just
      the second published case of an intraosseous schwannoma of the petrous apex and
      are the first to describe the entity using magnetic resonance imaging. By
      studying the computed tomography and magnetic resonance imaging features of this
      rare tumor, it is possible to suggest the diagnosis preoperatively.

PMID- 22470770
TI  - Lipoma arborescens of knee joint: role of imaging.
AB  - A 23 year old Asian female presented with swelling of right knee joint for 5
      years with history of exacerbations and remissions of symptoms. She was initially
      diagnosed as a case of suprapatellar bursitis based on clinical and X-ray
      findings. Further evaluation with higher imaging modalities was pathognomonic of
      lipoma arborescens. Patient underwent synovectomy and the diagnosis was confirmed
      histologically. We describe a histologically proven case of lipoma arborescens to
      highlight the imaging findings on X-ray, Ultrasound and Magnetic resonance
      imaging with arthroscopic correlation. The unique feature of this case report is
      multimodality imaging correlation with arthroscopy and histopathology findings.
      We have highlighted the pathognomonic imaging findings of this rare but benign
      intra-articular lesion and also discussed the differential diagnosis in detail.

PMID- 22470771
TI  - Endovascular stent graft for post-traumatic superficial femoral artery
      pseudoaneurysms with arteriovenous fistula: 6 months follow-up of 2 cases.
AB  - Pseudoaneurysms are common vascular abnormalities due to disruption of the vessel
      wall. Pseudoaneurysm with arteriovenous fistula is a rare presentation.
      Complications associated with them develop unpredictably and carry a high
      mortality rate. Traditionally pseudoaneurysms have been treated surgically.
      However, with the advent of new interventional techniques, management using
      endovascular approach have gained popularity in treating pseudoaneurysms. Here,
      we present two cases of large pseudoaneurysms with arteriovenous fistula treated
      by percutaneous stent graft. Present studies on pseudoaneurysms are all either
      iatrogenic or secondary to nephrologic dialysis treatment and only few present
      studies exist describing such large post-traumatic femoral pseudoaneurysms with
      arteriovenous fistulas were treated successfully by stent grafting through
      femoral approach, with good patency at 6 months follow up.

PMID- 22470772
TI  - Benign breast cyst without associated gynecomastia in a male patient: a case
      report.
AB  - Benign simple breast cysts are commonly seen in female breasts and can present as
      palpable masses. They are distinctly uncommon, however, in the male breast. We
      report a case of simple benign cyst of the breast in a 58-year-old man newly
      diagnosed with mantel cell lymphoma. The cyst was first identified incidentally
      on a staging contrast-enhanced chest computed tomography. Further evaluation with
      mammography and ultrasound revealed a mass that would be typically characterized
      as a benign simple cyst, but was biopsied since cysts are not known to occur in
      male breasts. Pathology results from ultrasound-guided core needle biopsy
      revealed benign cyst and focal fibrosis which was concordant with the imaging
      findings. In this case report, we will briefly discuss breast cysts in men and
      their imaging features including mammography and ultrasound.

PMID- 22470774
TI  - A quick look back--2011 journal resume.
AB  - This is a quick retrospective view back to the year 2011, summarizing the
      journal's experience, demonstrating submission statistics of the Journal of
      Radiology Case Reports and journal updates planned for the year 2012.

PMID- 22470775
TI  - Orbital plasmablastic lymphoma with remission following chemotherapy.
AB  - We report the case of a middle-aged HIV-positive man who presented with proptosis
      and retro-ocular pain. On CT and MR imaging, a retro-orbital enhancing mass was
      seen, and PET/CT revealed this lesion as well as a similarly characterized mass
      in the nasopharynx to be hypermetabolic. Biopsy and subsequent pathological
      characterization revealed this mass to be plasmablastic lymphoma (PBL), a rare
      form of non-Hodgkin's lymphoma associated with HIV-infection. PBL is a diffuse B
      cell lymphoma with characteristic cell marker patterns. The most common site of
      this malignancy is within the oral cavity. This case constitutes an unusual
      orbital manifestation of plasmablastic lymphoma as well as an unusual case in its
      response to chemotherapy. This case illustrates the importance of functional
      imaging with PET/CT in the diagnosis, management, and follow-up of plasmablastic
      lymphoma.

PMID- 22470776
TI  - A case of clear cell sarcoma of the kidney.
AB  - Clear cell renal sarcoma is a rare tumor and comprises 4% of primary pediatric
      malignant renal tumors. It is known as an aggressive tumor with poor prognosis.
      Clinically and radiographically, it resembles Wilms tumor. We present a case of a
      child with an abdominal mass that was diagnosed as clear cell sarcoma of her
      right kidney.

PMID- 22470777
TI  - Value of T2-mapping and DWI in the diagnosis of early knee cartilage injury.
AB  - OBJECTIVE: To study the value of T2-mapping and diffusion weighted imaging (DWI)
      in the diagnosis of early injury of knee cartilage. METHODS: Seventy-two
      subjects, including healthy group (n=30) and early cartilage injury group (n=42),
      were tested on MR scans with T2-mapping and DWI. T2 and apparent diffusion
      coefficient (ADC) values of cartilage were measured after being processed at the
      workstation, and the differences were statistically analyzed between the two
      groups. RESULTS: The mean T2 and ADC values of cartilage in early injury group
      and health group were respectively 51.58+/-4.15 ms and 1.78+/-0.35 *10(-3)
      mm(2)/s, 39.54+/-4.02 ms and 1.44+/-0.17 *10(-3) mm(2)/s. There was significant
      difference between the values of T2 and ADC. CONCLUSION: T2 and ADC values in
      early cartilage injury have obviously increased. T2-mapping and DWI have high
      clinical value in the diagnosis of early articular cartilage injury.

PMID- 22470778
TI  - Alcohol sclerosis of a giant liver cyst following failed deroofings.
AB  - Percutaneous alcohol sclerotherapy for simple liver cysts is an established and
      safe procedure. We report alcohol ablation of a very large (5.5 liters) liver
      cyst that had failed laparoscopic deroofing procedures twice. The cyst responded
      to multisession alcohol sclerotherapy.

PMID- 22470779
TI  - Educational treasures in radiology: a free online program for Radiology Boards
      preparation.
AB  - PURPOSE: An objective tool is desired, which optimally prepares for Radiology
      boards examination. Such program should prepare examinees with pertinent
      radiological contents and simulations as expected in the real examination.
      BACKGROUND: Many countries require written boards examinations for Radiology
      certification eligibility. No objective measure exists to tell if the examinee is
      ready to pass the exam or not. Time pressure and computer environment might be
      unfamiliar to examinees. Traditional preparation lectures don't simulate the
      "real" Radiology exam because they don't provide the special environment with
      multiple choice questions and timing. MATERIALS AND METHODS: This online program
      consists of 4 parts. The entry section allows to create questions with additional
      fields for comprehensive information. Sections include
      Pediatrics/Mammography/GI/IR/Nucs/Thoracic/Musculoskeletal/GU/Neuro/Ultrasound/Ca
      diac/OB/GYN and Miscellaneous. Experienced radiologists and educators evaluate
      and release/delete these entries in the administrator section. In the exam
      section users can create (un)timed customized exams for individual needs and
      learning pace. Exams can either include all sections or only specific sections to
      gear learning towards areas with weaker performance. Comprehensive statistics
      unveil the user's strengths and weaknesses to help focussing on "weak" areas. In
      the search section a comprehensive search and review can be performed by
      searching the entire database for keywords/topics or only searching within
      specific sections. CONCLUSION: www.RadiologyBoards.org is a new working concept
      of Radiology boards preparation to detect and improve the examinee's weaknesses
      and finally to increase the examinee's confidence level for the final exam. It is
      beneficial for Radiology residents and also board certified radiologists to
      refresh/maintain radiological knowledge.

PMID- 22470780
TI  - Thyroid abscess as a complication of bacterial throat infection.
AB  - Thyroid abscesses are rare complications of neck infections. We report the case
      of a teenager who developed increasing neck pain and swelling following treatment
      for a Streptococcus throat infection. Imaging demonstrated a complex fluid
      collection in the left thyroid lobe. Ultrasound guided aspiration was performed
      for diagnostic purposes, yielding purulent fluid that grew multiple bacterial
      species. Following initial antibiotic treatment, the patient underwent definitive
      surgical management. Underlying risk factors and imaging techniques will be
      reviewed.

PMID- 22470781
TI  - Diffusion restriction in thrombosed superior ophthalmic veins: two cases of
      diverse etiology and literature review.
AB  - Thrombosis of superior ophthalmic veins (SOV) is a well known entity occurring
      secondary to varied etiologies. We describe diffusion restriction in thrombosed
      SOV in two cases of different etiologies- bilateral involvement in a patient with
      septic cavernous sinus thrombosis (CST) and another where embolisation of an
      indirect carotico-cavernous fistula (CCF) resulted in complete SOV thrombosis
      accompanied by clinical worsening. Our cases add to the limited literature on
      diffusion findings in SOV thrombosis.

PMID- 22470782
TI  - Magnetic resonance imaging in Hirayama disease.
AB  - Hirayama disease (HD) is a rare type of cervical myelopathy related to flexion of
      the neck characterized by progressive muscular weakness and atrophy of the distal
      upper limbs most frequently seen in young males. HD is thought to be secondary to
      an abnormal anterior displacement of the posterior dura with secondary
      compression of the lower cervical spinal cord and chronic injury to the anterior
      gray matter horns. We present two patients with HD and discuss its
      pathophysiology and imaging characteristics.

PMID- 22470783
TI  - Hypertrophic olivary degeneration after resection of a pontine cavernous
      malformation: a case report.
AB  - We report the case of a 35 year old African American female who developed
      hypertrophic olivary degeneration secondary to resection of a pontine cavernous
      malformation. The patient initially complained of headaches and diplopia.
      Unenhanced computed tomography (CT) and magnetic resonance images (MRI) of the
      brain revealed a left pontine cavernous malformation with scattered foci of
      recent and remote hemorrhage. The patient subsequently underwent surgical
      resection of the lesion. Follow up MRI 7 months post surgery demonstrated
      hypertrophy and T2 signal hyperintensity in the ipsilateral inferior olivary
      nucleus secondary to hypertrophic olivary degeneration. Familiarity with this
      diagnosis and its imaging characteristics is required of the radiologist to
      prevent erroneous diagnoses of other pathology.

PMID- 22470784
TI  - An impressive ceiling.

PMID- 22470785
TI  - Right isomerism with complex cardiac anomalies presenting with dysphagia--a case
      report.
AB  - Isomerism or Heterotaxy syndromes are rare multifaceted congenital anomalies with
      multi-system involvement. Grouped under the broad category of Situs Ambiguous
      defects, these often pose diagnostic difficulties due to their varied and
      confusing anatomy. Since patients rarely survive into adulthood due to
      cardiovascular complications, the etiology and natural history of such conditions
      are not fully understood. Imaging provides the most accurate non invasive method
      for diagnosis and thereby, prognosis in such cases. We present a case of right
      sided Isomerism with complex cardiac anomalies in a 17 year old adolescent, who
      presented with dysphagia as one of the main complaints. Multi modality imaging
      demonstrated the intricate abnormalities in vital systems.

PMID- 22470787
TI  - Case report of xanthogranulomatous cholecystitis, review of its sonographic and
      magnetic resonance findings, and distinction from other gallbladder pathology.
AB  - A case of xanthogranulomatous cholecystitis is presented with a brief review of
      its sonographic and magnetic resonance features. These imaging features are also
      compared to those seen in gallbladder adenomyomatosis and gallbladder carcinoma.
      While there are many overlapping imaging findings in these entities, it is
      important to recognize distinguishing characteristics so a correct surgical
      approach is chosen. Laparoscopic cholecystectomy attempted with existing
      xanthogranulomatous cholecystitis has an increased surgical complication rate
      compared to open cholecystectomy and often necessitates intraoperative conversion
      to open cholecystectomy.

PMID- 22470786
TI  - Ruptured intracranial dermoid cyst manifesting as new onset seizure: a case
      report.
AB  - Intracranial dermoid cysts are rare tumors derived from ectopic epithelial cells.
      They are slow-growing benign entities, but can cause significant morbidity
      through compression of neurovascular structures and, rarely, rupture into the
      subarachnoid space. We present a rare case of a spontaneously ruptured
      intracranial dermoid cyst presenting as new onset seizures due to chemical
      meningitis caused by dissemination of fat droplets.

PMID- 22470788
TI  - Umbilical concretion.
AB  - Umbilical concretion is a rarely encountered benign entity. Concretions typically
      form within an umbilical cleft which is unusually deep and consist of
      keratinaceous and sebaceous material. Lack of attention to umbilical hygiene
      usually plays a role in their formation. Concretions are generally asymptomatic
      and may only present clinically when complicated by inflammation or infection.
      Their appearance on imaging studies may be problematic for the radiologist given
      their rarity, particularly in the setting of a known or suspected intra-abdominal
      malignancy.

PMID- 22470789
TI  - Extraperitoneal urinary bladder perforation detected by FDG PET/CT.
AB  - Accurate localization of areas of increased metabolic activity on PET only
      imaging can be challenging. Fusion of PET with CT imaging provides anatomic
      detail which aids in localization of functional information. As a result, the
      overall sensitivity and specificity of information provided by PET or CT alone is
      improved with combined PET/CT resulting in improved diagnosis and patient
      management. We report a case of an unexpected emergent finding of urinary bladder
      perforation on PET/CT to stress the importance of accurately interpreting the
      anatomic and functional data. To our knowledge, diagnosis of bladder perforation
      on PET/CT has not been previously reported in the literature. Failure to
      recognize such complications may lead to adverse outcomes.

PMID- 22470790
TI  - Primary breast lymphoma: a rare entity.
AB  - In the past two decades there has been an increase in the incidence of non
      Hodgkin lymphoma and Hodgkin disease. This has been accompanied by an increase in
      the numbers of extranodal lymphoma. Despite this primary breast lymphoma is a
      rare disease. We present a case of a 74 year old female with primary breast
      lymphoma. Methods of imaging including PET/CT are discussed. Criteria for
      diagnosing primary breast lymphoma are presented. In addition diagnostic methods
      and therapeutic options are considered.

PMID- 22470791
TI  - Pediatric holohemispheric developmental venous anomaly: definitive
      characterization by 3D susceptibility weighted magnetic resonance angiography.
AB  - We present a case of an incidentally discovered holohemispheric developmental
      venous anomaly (DVA) in a 12 year old, conclusively characterized by 3D T2* multi
      echo sequence susceptibility weighted angiographic imaging (SWAN). For the
      evaluation of head trauma, abnormal right intraparenchymal and periventricular
      vascularity was identified by a non contrast head CT scan. Conventional MRI
      sequences revealed prominent veins with findings suspicious of a DVA. A
      definitive diagnosis was made by identifying angiographic features typical for
      DVA by augmented susceptibility weighted angiographic imaging. Using this
      sequence the entire hemispheric extent of the anomaly without complicating
      features was definitively characterized, negating the need for a catheter based
      angiographic study. A holohemispheric DVA in a child to our knowledge has not
      been previously described.

PMID- 22470792
TI  - Rescue from hemodialysis by late recanalization of renal artery occlusion.
AB  - We report on a patient with terminal renal insufficiency undergoing hemodialysis
      since four months. Imaging studies showed complete renal artery occlusion of a
      single kidney with collateral perfusion. Interventional recanalization of the
      renal artery was successful with a drop of serum creatinine from 1138 to 163
      mol/l sparing the patient from further hemodialysis.

PMID- 22470793
TI  - Particle disease on fluoride-18 (NaF) PET/CT imaging.
AB  - Particle disease is a loss of bone that commonly occurs about five years after
      arthroplasty. The cause is secondary to microabrasive wear and shedding of any
      portion of the prosthesis, and the microscopic foreign bodies activate
      inflammation which can lead to pain. This report describes the imaging findings
      of an 80-year-old female with particle disease detected with 18F-fluoride PET/CT.

PMID- 22470794
TI  - Cystic lymphangioma of the lesser curvature of the stomach--case report.
AB  - We report a case of a cystic lymphangioma arising from the lesser curvature of
      the stomach in a 16-year-old female who initially presented with abdominal pain,
      nausea, and emesis. Contrast enhanced computed tomography and magnetic resonance
      imaging revealed a large, thin-walled multicystic mass located anteromedial to
      the stomach, which was predominately supplied by the left gastric artery. Given
      the imaging appearance and location, a mesenteric cyst, specifically a cystic
      lymphangioma, was considered. Lymphangioma was the final pathological diagnosis
      after laparotomy with complete resection of the cystic abdominal mass.

PMID- 22470795
TI  - Local recurrence and multi-organ metastasis of primary retroperitoneal
      leiomyosarcoma in unusual locations after surgical resection.
AB  - We report a case of retroperitoneal leiomyosarcoma in a 52-year-old woman, who
      developed local recurrence, pulmonary, hepatic, peritoneal, pancreatic,
      subcutaneous and intramuscular metastases two years after surgical resection of
      the primary tumor. Metastasis to the pancreas, subcutaneous or muscular tissue is
      very rare; however, presence of a lesion in these locations in a known case of
      leiomyosarcoma might indicate a metastatic tumor deposit.

PMID- 22470796
TI  - Impact of geometric mean imaging in the accurate determination of partial
      function in MAG3 renal scanning in a patient with retroperitoneal mass.
AB  - Liposarcoma frequently occurs in the retroperitoneum and lower extremities,
      accounting for 20% of all mesenchymal malignancies. Liposarcomas vary by
      histology and can be classified into four types. Those four types are well
      differentiated, myxoid/round cell, pleomorphic and dedifferentiated. Due to
      retroperitoneal location of this tumor, it is expected to affect the kidney
      position. Renography has provided a unique tool for noninvasive evaluation of
      various functional parameters e.g. relative renal function. Most renography
      studies are carried out using the posterior view, under the assumption that the
      depths of both kidneys are similar so that the radiotracer counts in the region
      of interest will be attenuated to the same extent. Errors in estimation of the
      relative renal function may arise if the kidneys are at different depths e.g.
      secondary to a pushing tumor. Geometric mean imaging from combined anterior and
      posterior views helps to overcome this issue. This case shows the impact of
      geometric mean imaging in the truthful determination of partial function in
      patients with retroperitoneal liposarcoma.

PMID- 22470797
TI  - Plunging ranula.
AB  - Plunging ranulas are rare cystic masses in the neck that are mucous retention
      pseudocysts from an obstructed sublingual gland. They "plunge" by extending
      inferiorly beyond the free edge of the mylohyoid muscle, or through a dehiscence
      of the muscle itself, to enter the submandibular space. Imaging demonstrates a
      simple cystic lesion in the characteristic location and can be used to delineate
      relevant surgical anatomy. Surgical excision of the collection and the involved
      sublingual gland is performed for definitive treatment. We present a case of
      plunging ranula in a 44 year old female who presented with a painless, slowly
      enlarged neck mass. Plunging ranulas should be considered in the differential
      diagnosis of cystic neck masses, specifically when seen extending over, or
      through, the mylohyoid muscle.

PMID- 22470798
TI  - Calcific tendonitis of the tibialis posterior tendon at the navicular attachment.
AB  - Calcific tendinosis (tendonosis/tendonitis) is a condition which results from the
      deposition of calcium hydroxyapatite crystals in any tendon of the body. Calcific
      tendonitis usually presents with pain, which can be exacerbated by prolonged use
      of the affected tendon. We report a case of calcific tendinosis in the posterior
      tibialis tendon at the navicular insertion. The pathology is rare in the foot,
      and extremely rare in the tibialis posterior tendon, indeed there are only 2
      reported in the published literature. This case report highlights the need to
      consider calcific tendinosis in the foot despite its rarity. If this diagnosis is
      considered early, appropriate investigations can then be requested and
      unnecessary biopsies, use of antibiotics and surgery can be avoided. We also
      discuss possible causes of calcific tendinosis in the tibialis posterior tendon,
      the role of imaging modalities and review treatment methods.

PMID- 22470799
TI  - Avascular necrosis of the capitate.
AB  - Avascular necrosis of the capitate is a rare entity. The most common reported
      etiology is trauma. We report a case of avascular necrosis of the capitate in a
      patient with chronic wrist pain that began after a single episode of remote
      trauma.

PMID- 22470801
TI  - Acrokeratosis paraneoplastica (Bazex syndrome): report of a case associated with
      small cell lung carcinoma and review of the literature.
AB  - Acrokeratosis paraneoplastic (Bazex syndrome) is a rare, but distinctive
      paraneoplastic dermatosis characterized by erythematosquamous lesions located at
      the acral sites and is most commonly associated with carcinomas of the upper
      aerodigestive tract. We report a 58-year-old female with a history of a pigmented
      rash on her extremities, thick keratotic plaques on her hands, and brittle nails.
      Chest imaging revealed a right upper lobe mass that was proven to be small cell
      lung carcinoma. While Bazex syndrome has been described in the dermatology
      literature, it is also important for the radiologist to be aware of this entity
      and its common presentations.

PMID- 22470802
TI  - Accessory parotid gland with ectopic fistulous duct--diagnosis by
      ultrasonography, digital fistulography, digital sialography and CT fistulography.
      A case report and review of current literature.
AB  - Accessory parotid glands are a common clinical occurrence and usually drain into
      the main Stenson's duct by small ductules and thereby, into the buccal cavity.
      Presence of an accessory parotid gland with an ectopic fistulous duct is a rare
      occurrence. We present the imaging findings in a case of right accessory parotid
      gland with ectopic fistulous duct associated with bilateral pre-aural appendages.
      Diagnostic workup was done by ultrasonography, sono-fistulography, contrast
      digital fistulography, contrast digital sialography and computed tomography
      fistulography. Imaging showed a right accessory parotid gland lying anterior to
      and separate from the main parotid gland draining via an ectopic fistulous duct
      opening over the right cheek. The child was managed surgically by internalisation
      of the duct to open into the buccal mucosa and excision of pre-aural appendages.

PMID- 22470803
TI  - Spontaneous talar and calcaneal fracture in rheumatoid arthritis: a case report.
AB  - Rheumatoid arthritis (RA) leads to a progressive weakening of the skeleton which
      may result in bone fractures. However, spontaneous fractures (exclusive of stress
      fractures, vertebral collapse, and superficial articular fragmentation) in
      patients with rheumatoid arthritis have been only occasionally reported in the
      medical literature. A case of spontaneous talar and calcaneal fracture in
      rheumatoid arthritis is described. Bone lesions were identified on radiographs,
      MR images and scintigraphy in a patient with right ankle pain. The absence of
      episodes of acute trauma, and the presence of acute clinical manifestations
      should guide the clinical suspicion.

PMID- 22470804
TI  - Solid pseudopapillary tumor of the pancreas: a rare and probably misdiagnosed
      neoplasm.
AB  - Solid Pseudopapillary Tumor of the pancreas is a rare nonfunctioning tumor. It is
      considered a low-grade malignancy that is apparently curable with surgical
      complete excision in most instances. We present a case of solid pseudopapillary
      pancreatic tumor that represented a challenge to the radiologists. This case
      highlights its possible various appearances and the need to the radiologist to be
      familiar with them.

PMID- 22470805
TI  - Retroperitoneal fibrosis as a cause of positive FDG PET/CT.
AB  - This article educates the reader on idiopathic retroperitoneal fibrosis and
      emphasizes the importance of considering conditions that mimic this disease on
      PET/CT through an illustrative case of a 58 year-old man presenting with
      intermittent abdominal, back, and scrotal pain undergoing successive PET/CT
      scans, both for diagnosis and following treatment.

PMID- 22470806
TI  - White matter microsusceptibility changes in patients with hepatic encephalopathy.
AB  - We report a new radiological finding in two patients with hepatic encephalopathy.
      A new susceptibility-weighted (SWI) magnetic resonance imaging sequence revealed
      multiple bilateral microsusceptibility changes in the corpus callosum and white
      matter, while the conventional T1 and T2 weighted images were unremarkable. We
      postulate that the etiology of the microsusceptibility changes may be related to
      hepatic coagulopathy and other factors, such as impaired cerebral blood flow and
      brain edema.

PMID- 22470807
TI  - Pancreatic arteriovenous malformation: a case report and literature review.
AB  - Most pancreatic arteriovenous malformations (PAVM) present due to
      gastrointestinal bleeding or abdominal pain, but these patients may be
      asymptomatic. Increased portal vein flow from these malformations can lead to
      portal hypertension and gastrointestinal bleeding. Diagnosis is often made by
      imaging, and early diagnosis has led to successful surgical resection or
      percutaneous embolization. We report a patient with PAVM, diagnosed by CT and
      angiography, who has remained asymptomatic for 2 years without treatment.

PMID- 22470808
TI  - Multislice CT imaging of ruptured left sinus of Valsalva aneurysm with fistulous
      track between left sinus and right atrium.
AB  - Sinus of valsalva aneurysm is a rare condition arising from any of the three
      aortic sinuses. Among them, an aneurysm arising from the left coronary sinus is
      the rarest. Most of these cases were earlier diagnosed using echocardiography and
      conventional angiography. But with the availability of advanced imaging
      modalities like 64 slice cardiac CT and MR modalities, this condition can be
      accurately assessed noninvasively. We report a case of ruptured aneurysm
      originating from the left coronary sinus with a long windsock type of fistulous
      track between the aneurysm and right atrium evaluated by 64 slice cardiac CT
      imaging. This was later confirmed perioperatively.

PMID- 22470809
TI  - Sesamoid ossicles within the nuchal ligament: a report of two cases and review of
      the literature.
AB  - Sesamoid ossicles are ovoid or round nodular small bones found usually within a
      joint or tendon of the upper and lower limb and rarely at other regions. They are
      usually asymptomatic, resulting in an increased propensity to injuries. We report
      on two cases where sesamoid ossicles were detected within the nuchal ligament.
      The first one was a 55-years-old Caucasian male office employee, complaining of
      chronic pain in the cervical spine region accompanied by numbness of the left
      upper limb. During the routine lateral X-ray imaging two sesamoid ossicles were
      found within the nuchal ligament at the C4 and C5 spinous processes level. The
      second case was a 64-years-old Caucasian female store employee, complaining of
      chronic cervical spine pain. The routine lateral X-ray exhibited two sesamoid
      ossicles within the nuchal ligament at the C5 and C6 spinous processes level.
      Sesamoid ossicles found in the nuchal ligament in rare cases may become
      symptomatic and the pathogenesis mechanism should be differentially diagnosed by
      the physician. We discuss the precise morphology of the trait, the possible
      etiological mechanisms for their appearance, the histological features, as well
      as differential diagnosis.

PMID- 22470810
TI  - CPPD crowned dens syndrome with clivus destruction: a case report.
AB  - We report a case of CPPD crowned dens syndrome in an 87 year white old male with
      a known history of pseudogout, with clinical and radiological features
      characteristic of this syndrome. Interestingly, there was significant mass effect
      on the clivus, with clivus erosion and destruction, a finding that has not
      previously been described with this syndrome. The clinical and radiological
      characteristics of Crowned Dens syndrome, as well as CPPD are reviewed. We
      suggest that CPPD crowned dens syndrome may be included in the differential
      diagnosis when clivus destruction or erosion, in association with a soft tissue
      mass with calcification, is seen.

PMID- 22470811
TI  - An unusual cause of widespread lytic bone lesions caused by sarcoidosis.
AB  - We present a case of a 59 year old asymptomatic lady who was found to have
      incidental findings of pulmonary, osseous and hepatic involvement with
      sarcoidosis. The osseous lesions were lytic and involved unusual sites such as
      the vertebrae and skull base. The initial clinical concern had been of multiple
      myeloma or disseminated metastases. Biopsy of material obtained following
      mediastinoscopy revealed chronic, non-necrotising granulomatous lymphadenopathy
      indicative of sarcoidosis. Cases such as this could greatly benefit from
      multidisciplinary team discussion particularly when the clinical picture is not
      typical of malignancy.

PMID- 22470812
TI  - Giant keloid of left buttock treated with post-excisional radiotherapy.
AB  - Keloids are defined as excessive scar tissue formation extending beyond the area
      of the original skin injury and occurring in predisposed individuals. While no
      single treatment has proven widely effective, several series report excellent
      outcomes for keloids with post-surgery radiation therapy as described in the
      literature. We present a patient with recurrent giant keloid of left buttock
      after several surgical removals, that at physical examination shows the size of
      40*22*10 cm in the largest dimension. Patient underwent a surgical excision of
      gluteal lesion and postoperative radiotherapy using photons at 8 MV of linear
      accelerator: the total dose delivered was 22 Gy in 11 days, with a daily fraction
      of 2 Gy. No relapse was showed at 36 months post-therapy. Several methods seem
      unsatisfactory for preventing keloid recurrence. The combination of surgery and
      adjuvant radiotherapy seems an excellent strategy to prevent recurrent disease.

PMID- 22470813
TI  - Inflammatory pseudotumor of the spleen: review of clinical presentation and
      diagnostic methods.
AB  - We describe a 91-year-old woman with a clinical history of invasive ductal
      carcinoma of the breast diagnosed in 1991 who was admitted because of dizziness,
      poor appetite, and some swelling and tenderness over her cheeks. The patient's
      initial work up revealed a 5-cm well-demarcated hypodense solid lesion in her
      spleen with abnormally intense uptake on PET/CT scan raising suspicion for
      malignancy i.e. breast metastasis versus lymphoma. Further review demonstrated
      the presence of this splenic lesion, though slightly smaller, on a CT scan from
      ten years earlier (2000). An ultrasonographic guided core needle splenic biopsy
      was performed and the pathology result revealed histological findings compatible
      with inflammatory pseudotumor of the spleen. As a result, unnecessary splenectomy
      was avoided.

PMID- 22470814
TI  - Critical pitfall: varices in cancer patients mimicking lymphadenopathy;
      differentiation of varicose veins and enlarged lymph nodes in routine staging.
AB  - Two patients, each with a history of multiple cancers, were referred to our
      institution for routine cancer staging. Contrast enhanced multislice-CT showed
      round and oval shaped inguinal and retroperitoneal masses in one patient and
      inguinal mass lesions in the other patient. The mass lesions were suspicious of
      lymphadenopathy related to cancer recurrence. Additional MR-Imaging, however,
      showed tortuous varicose veins as well as suspicious lymph nodes in one patient
      and solely venous convolutes in the other patient. Regarding the routine contrast
      enhanced CT-scan in the portovenous phase, varices showed no significant
      difference in radiodensity compared to enlarged lymph nodes.

PMID- 22470816
TI  - Editorial.

PMID- 22470815
TI  - Case report of idiopathic pulmonary haemosiderosis in a child with recurrent
      chest infections.
AB  - Idiopathic pulmonary haemosiderosis (IPH) is a rare condition that usually
      presents as a triad of haemoptysis, iron deficiency anaemia and pulmonary
      infiltrates. We report a case of IPH diagnosed in a 7 year old boy who had
      recurrent hospital admissions with severe chest infections and haemoptysis from
      his first few months of life. He was found to have microcytic hypochromic
      anaemia, diffuse infiltrate shadowing on his chest X-ray (CXR) and ground-glass
      opacification on his computed tomogram (CT). Perl's Prussian blue staining of his
      bronchoalveolar lavage fluid revealed haemosiderin-laden macrophage infiltration.
      After exclusion of infective, cardiac, immunological and glomerular causes, he
      was diagnosed with idiopathic pulmonary haemosiderosis. He has since been treated
      intermittently with steroids, which have failed to control his symptoms fully.

PMID- 22470818
TI  - Mentoring the "best and brightest" in maternal fetal medicine.

PMID- 22470817
TI  - Vasa previa.

PMID- 22470819
TI  - Prenatal diagnosis of genomic disorders and chromosome abnormalities using array
      based comparative genomic hybridization.
AB  - Cytogenetic analysis is a crucial tool of prenatal diagnosis. The ability to
      rapidly detect aneuploidy and identify small structural abnormalities of foetal
      chromosomes has been greatly improved by the use of molecular cytogenetic
      technologies. Microarray-based Comparative Genomic Hybridization (aCGH) has been
      recently employed in postnatal diagnosis of cryptic chromosomal aberrations, but
      use in prenatal diagnosis is still limited.We set-up a diagnostic protocol which
      uses aCGH technology on genomic DNA isolated from uncultured chorionic villus
      sampled at 11-12 week's gestation. We used a commercially targeted microarray
      (MDTelArray, Technogenetics Srl - Bouty Group, Sesto S. Giovanni, Milan, Italy)
      constituted by 167 genomic clones corresponding to 34 critical regions frequently
      involved in microdeletions and microduplications and 126 subtelomeric clones.
      Array validation has been carried-out via retrospective analysis of DNA isolated
      from a series of cytogenetically normal chorionic villus samples (CVS) and of DNA
      isolated from cytogenetically abnormal cultured amniocytes, CVS or peripheral
      blood. A pilot prospective study was undertaken analyzing 25 CVS obtained from
      foetuses at risk for chromosomal aberrations. aCGH results both for retrospective
      and prospective studies were in agreement with data obtained using "classical"
      cytogenetic analysis, and/or FISH analysis or DNA testing. Although these
      preliminary data support the usefulness of aCGH in prenatal diagnosis, further
      prospective studies are required to verify the feasibility of introducing this
      technique as part of the diagnostic armamentarium for identify affected foetuses.

PMID- 22470820
TI  - The use of pulsed-wave Doppler in prenatal diagnosis. An update.
AB  - Pulsed wave Doppler ultrasound of fetal vessels confirms the similarity of human
      fetal circulation to the experimental animal physiology, The result of a
      multitude of research articles in this field is the clinical use of various
      components of fetal circulation in perinatal medicine. Umbilical, uterine and
      fetal cerebral arteries as well as the fetal venous circulation show the
      potential of Doppler ultrasonography.

PMID- 22470821
TI  - Non-immune fetal hydrops: Are we doing the appropriate tests each time?
AB  - Non-immune fetal hydrops is diagnosed when there is fluid accumulation in more
      than one extravascular space. A long list of etiologies has been found in
      association with non-immune hydrops. Thorough investigations are needed to be
      able to identify an underlying cause. There are many recent reports indicating
      that non-immune hydrops can be an extreme presentation of a number of metabolic
      disorders, mostly lysosomal storage diseases. The fetal hydrops associated with
      metabolic disorders is usually severe with very thick skin, massive ascitis,
      other feature could be seen such as contracture deformities, skeletal
      abnormalities, hepatosplenomegaly, renal abnormalities, and enlarged nuchal
      translucency. The diagnosis of a metabolic disorder can be done by a variety of
      different tests: measuring the level of the specific enzyme or metabolite,
      histological examination of different organs, or mutation identification. An
      index case is usually needed to confirm the diagnosis. In-utero diagnosis of a
      metabolic disorder in the absence of an index case is difficult and only
      available in selected laboratories around the world. In populations with high
      consanguinity, these diseases are much more commonly present than what we might
      think. Routine screening for metabolic diseases especially lysosomal storage
      diseases should be considered in these populations, and definitely in cases of
      recurrent hydrops in the same family. More efforts should be spent on identifying
      causative mutations in different ethnic groups. Every effort should be made to
      identify the etiology in an index case in the family, as this might be the best
      opportunity for improving future care.

PMID- 22470822
TI  - The importance of early diagnosis in cesarean scar pregnancy.

PMID- 22470823
TI  - Hypoplastic left heart syndrome with intact atrial septum: case report.
AB  - OBJECTIVES: Hypoplastic left heart syndrome (HLHS) with an intact atrial septum
      (IAS) is a rare finding, reported in only 1% of pathologic specimens with
      hypoplasia of the aortic tract complex. In newborns with left heart obstruction,
      the existence of an interatrial communication is very important for oxygenated
      blood to be distributed to the body and to prevent pulmonary congestion. The
      ability to predict prenatally restriction of the atrial defect may allow earlier
      surgery to be planned. METHODS: We report a case of prenatal diagnosis of HLHS
      with a complete premature closure of the foramen ovale that was not detected by
      prenatal echocardiography. RESULTS AND CONCLUSION: The management of neonates
      with HLHS in the first days of life is crucial to the results of the first stage
      of the Norwood procedure. We suggest that delivery of the mother close to
      surgical centre and avoiding neonatal transfer improve the results, but
      stabilisation with prostaglandins and balancing of the systemic and pulmonary
      resistances are also important. A restrictive or closed atrial septal defect may
      contribute to haemodynamic instability in the first days of life. The ability to
      predict this complication prenatally may help in the immediate postnatal
      management of the affected infant.

PMID- 22470824
TI  - Atypical presentation of fetal inguino-scrotal hernia at 21 weeks of gestation: a
      case report.

PMID- 22470825
TI  - Transabdominal intralesional injection of Methotrexate in two angular live
      ectopic pregnancies.
AB  - The transvaginal injection of Methotrexate in the treatment of live ectopic
      pregnancy has been reported. The Authors report two cases of angular live ectopic
      pregnancies treated successfully with transabdominal injection of Methotrexate.

PMID- 22470826
TI  - Isolation of amniotic fluid-derived mesenchymal stem cells.

PMID- 22470827
TI  - A case report of a meiotic segregation study on a small supernumerary marker
      chromosome.
AB  - Small supernumerary marker chromosomes (sSMCs) have been described from all human
      chromosomes with different sizes and shapes. However, it is difficult to know the
      clinical manifestations associated with them, because such knowledge depends on
      the size, presence of euchromatic material, degree of mosaicism and/or
      uniparental disomy (UPD).A case report of a familial small supernumerary marker
      chromosome (sSMC) through a structural and a segregation study is reported.

PMID- 22470828
TI  - Fetal hepatic mesenchymal hamartoma: a case report.

PMID- 22470829
TI  - Prenatal Aneuploidies Computerized Screening (SCA TEST): a pilot study on 1000
      women.
AB  - The SCA-TEST, Prenatal Aneuploidies Screening, is an innovating program with very
      articulated and differentiated calculation potentials. It is a software which
      allows executing a sequence-like rational screening involving the ultrasound
      study of the first and second trimester. The program enables to execute a
      complete and different- levels combined screening, through very sophisticated
      mathematic analysis methods. In particular, it enables to make: a first trimester
      screening combining it with nuchal translucency, and biochemical parameters of
      free beta-hCG and PAPP-A; a second trimester screening by the evaluation of up to
      6 biometric parameters (biparietal diameter, cranial circumferentia, femur,
      humerus, pyelectasis and plica nucalis), and up to 7 associated morphologic
      parameters (hyperechogenic bowel, cardiac foci, interventricular defect,
      pericardial effusion, tricuspid valve regurgitation, right/left heart
      disproportion, and structural abnormalities). The purpose of the study was to
      present the performance of the SCA TEST in the second trimester of pregnancy
      through the evaluation of a prospective study performed in the period between
      April 2007 and December 2007 on 1000 women who underwent the SCA TEST followed by
      amniocentesis. Studying all the cardiovascular and non-cardiovascular markers,
      SCA TEST made it possible to identify 62.5% fetuses affected by Trisomy 21 with a
      specificity of 94.6%, and a 5.4% of false positive. Considering only women older
      than 35 years the detection rate reaches 80% with a 7.8% of false positive. The
      statistical analysis confirmed that the second trimester screening gives
      essential information regarding the aneuploidia risks in particular in high risk
      women, and in those who did not perform first trimester screening.

PMID- 22470830
TI  - Nuchal cord entanglement and outcome of labour induction.
AB  - AIM OF THE STUDY: To assess whether nuchal cord entanglement would affect the
      outcome of elective labour induction. METHOD: In a group of pregnant women, the
      outcome of elective labour induction was evaluated in relation to a list of
      possibly related variables, including the presence of nuchal cord at delivery.
      RESULTS: Overall 184 women submitted to induction of labour were prospectively
      examined. Vaginal delivery was observed in 141 women (76.6%), with 105 of them
      (or 57%) having been delivered within 24 h from induction. At delivery, nuchal
      cord was detected in 59 out of 184 neonates (32%). Among the pre-induction and
      post-induction variables, only parity >= 1 (OR 3.44; 95% CI: 1.67-7.06) and a
      Bishop score >= 5 (OR 3.59; 95% CI: 1.93-6.70) appeared statistically associated
      with the success of induction. The chance of vaginal delivery within 24 hours
      from labour induction (31/59 or 53% vs 74/125 or 59%; OR: 0.92; 95% CI: 0.75
      1.12) were comparable among the neonates with and without nuchal cord at birth.
      CONCLUSIONS: In women undergoing cervical ripening, multiparity and a favourable
      cervical score seem the only factors that predict a successful induction. An
      entangled cord around the fetal neck does not seem to increase the risk of
      induction failure.

PMID- 22470831
TI  - Fetal malformations and fetal death in a case of parental thrombophilia.

PMID- 22470832
TI  - Clinical characteristics and genetic variability of human rhinovirus in Mexico.
AB  - Human rhinovirus (HRV) is a leading cause of acute respiratory infection (ARI) in
      young children and infants worldwide and has a high impact on morbidity and
      mortality in this population. Initially, HRV was classified into two species: HRV
      A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV
      D, were identified. In Mexico, there is little information about the role of HRV
      as a cause of ARI, and the presence and importance of species such as HRV-C are
      not known. The aim of this study was to determine the clinical characteristics
      and genetic variability of HRV in Mexican children. Genetic characterization was
      carried out by phylogenetic analysis of the 5'-nontranslated region (5'-NTR) of
      the HRV genome. The results show that the newly identified HRV-C is circulating
      in Mexican children more frequently than HRV-B but not as frequently as HRV-A,
      which was the most frequent species. Most of the cases of the three species of
      HRV were in children under 2 years of age, and all species were associated with
      very mild and moderate ARI.

PMID- 22470833
TI  - Back to BAC: the use of infectious clone technologies for viral mutagenesis.
AB  - Bacterial artificial chromosome (BAC) vectors were first developed to facilitate
      the propagation and manipulation of large DNA fragments in molecular biology
      studies for uses such as genome sequencing projects and genetic disease models.
      To facilitate these studies, methodologies have been developed to introduce
      specific mutations that can be directly applied to the mutagenesis of infectious
      clones (icBAC) using BAC technologies. This has resulted in rapid identification
      of gene function and expression at unprecedented rates. Here we review the major
      developments in BAC mutagenesis in vitro. This review summarises the technologies
      used to construct and introduce mutations into herpesvirus icBAC. It also
      explores developing technologies likely to provide the next leap in understanding
      these important viruses.

PMID- 22470834
TI  - Emerging viruses in the Felidae: shifting paradigms.
AB  - The domestic cat is afflicted with multiple viruses that serve as powerful models
      for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause
      these diseases have been studied for decades revealing detailed insight
      concerning transmission, virulence, origins and pathogenesis. Here we review
      recent genetic advances that have questioned traditional wisdom regarding the
      origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic
      potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae
      species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune
      impairment to domestic cats rather than other Felidae species. The most recent
      interpretations indicate important new evolutionary conclusions implicating these
      deadly infectious agents in domestic and non-domestic felids.

PMID- 22470835
TI  - Filovirus entry: a novelty in the viral fusion world.
AB  - Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of
      negative strand RNA viruses infect a broad range of mammalian cells. Recent
      studies indicate that cellular entry of this family of viruses requires a series
      of cellular protein interactions and molecular mechanisms, some of which are
      unique to filoviruses and others are commonly used by all viral glycoproteins.
      Details of this entry pathway are highlighted here. Virus entry into cells is
      initiated by the interaction of the viral glycoprotein(1) subunit (GP(1)) with
      both adherence factors and one or more receptors on the surface of host cells. On
      epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for
      this family of viruses, but the cell surface receptors in other cell types remain
      unidentified. Upon receptor binding, the virus is internalized into endosomes
      primarily via macropinocytosis, but perhaps by other mechanisms as well. Within
      the acidified endosome, the heavily glycosylated GP(1) is cleaved to a smaller
      form by the low pH-dependent cellular proteases Cathepsin L and B, exposing
      residues in the receptor binding site (RBS). Details of the molecular events
      following cathepsin-dependent trimming of GP(1) are currently incomplete;
      however, the processed GP(1) specifically interacts with endosomal/lysosomal
      membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1
      is required for productive infection, suggesting that GP/NPC1 interactions may be
      an important late step in the entry process. Additional events such as further
      GP(1) processing and/or reducing events may also be required to generate a fusion
      ready form of the glycoprotein. Once this has been achieved, sequences in the
      filovirus GP(2) subunit mediate viral/cellular membrane fusion via mechanisms
      similar to those previously described for other enveloped viruses. This multi
      step entry pathway highlights the complex and highly orchestrated path of
      internalization and fusion that appears unique for filoviruses.

PMID- 22470836
TI  - A plea for caution: huge risks associated with lab-bred flu.
AB  - I wish to express concern about the maintenance of laboratory strains of H5N1
      influenza viruses that might be adapted for transmission among humans.

PMID- 22470839
TI  - Studies on strains of Streptococcus mutans isolated from caries-active and caries
      free individuals in Iceland.
AB  - BACKGROUND: Dental caries has been strongly associated with mutans streptococci,
      particularly Streptococcus mutans and S. sobrinus. Many studies have linked these
      organisms to the carious process and counts of mutans streptococci have been used
      to monitor caries risk. The high levels of caries generally found in Iceland have
      enabled several studies to be performed on the variation within strains of S.
      mutans. METHODS: This paper reports some studies showing phenotypic differences
      between strains of S. mutans that were related to whether the strain was isolated
      from an individual with active caries or from a caries-free subject. RESULTS:
      Strains from individuals with active caries generally adhered better to apatite,
      were more vigorous in decalcifying apatite and had bacteriocin-like activity that
      was likely to help the strain compete successfully with other strains, for
      example in the dental plaque biofilm. CONCLUSIONS: Phenotypic differences exist
      between strains of S. mutans depending on the caries activity of the individual
      from whom the strain was isolated.

PMID- 22470838
TI  - Novel approaches to inhibit HIV entry.
AB  - Human Immunodeficiency Virus (HIV) entry into target cells is a multi-step
      process involving binding of the viral glycoprotein, Env, to its receptor CD4 and
      a coreceptor-either CCR5 or CXCR4. Understanding the means by which HIV enters
      cells has led to the identification of genetic polymorphisms, such as the 32 base
      pair deletion in the ccr5 gene (ccr5?32) that confers resistance to infection in
      homozygous individuals, and has also resulted in the development of entry
      inhibitors-small molecule antagonists that block infection at the entry step. The
      recent demonstration of long-term control of HIV infection in a leukemic patient
      following a hematopoietic stem cell transplant using cells from a ccr5?32
      homozygous donor highlights the important role of the HIV entry in maintaining an
      established infection and has led to a number of attempts to treat HIV infection
      by genetically modifying the ccr5 gene. In this review, we describe the HIV entry
      process and provide an overview of the different classes of approved HIV entry
      inhibitors while highlighting novel genetic strategies aimed at blocking HIV
      infection at the level of entry.

PMID- 22470837
TI  - Henipavirus mediated membrane fusion, virus entry and targeted therapeutics.
AB  - The Paramyxoviridae genus Henipavirus is presently represented by the type
      species Hendra and Nipah viruses which are both recently emerged zoonotic viral
      pathogens responsible for repeated outbreaks associated with high morbidity and
      mortality in Australia, Southeast Asia, India and Bangladesh. These enveloped
      viruses bind and enter host target cells through the coordinated activities of
      their attachment (G) and class I fusion (F) envelope glycoproteins. The
      henipavirus G glycoprotein interacts with host cellular B class ephrins,
      triggering conformational alterations in G that lead to the activation of the F
      glycoprotein, which facilitates the membrane fusion process. Using the recently
      published structures of HeV-G and NiV-G and other paramyxovirus glycoproteins, we
      review the features of the henipavirus envelope glycoproteins that appear
      essential for mediating the viral fusion process, including receptor binding, G-F
      interaction, F activation, with an emphasis on G and the mutations that disrupt
      viral infectivity. Finally, recent candidate therapeutics for henipavirus
      mediated disease are summarized in light of their ability to inhibit HeV and NiV
      entry by targeting their G and F glycoproteins.

PMID- 22470840
TI  - STING mediates neuronal innate immune response following Japanese encephalitis
      virus infection.
AB  - Flavivirus-mediated inflammation causes neuronal death, but whether the infected
      neurons can evoke an innate immune response to elicit their own protection, is
      unknown. In an earlier study we have shown that neuronal RIG-I, play a
      significant role in inducing production and release of molecules that are related
      to inflammation. In this study, using a neuronal cell line, we show that RIG-I
      acts with STING in a concerted manner following its interaction with Japanese
      encephalitis viral RNA to induce a type 1 interferon response. Knock-down of
      STING showed that the expressions of various inflammatory signaling molecules
      were down-regulated along with increased intracellular viral load. Alternatively,
      over-expressing STING decreased intracellular viral load. Our results indicate
      that at the sub-cellular level, interaction between the pattern recognition
      receptor RIG-I and the adapter molecule STING, is a major contributor to elicit
      immunological responses involving the type 1 interferons in neurons following JEV
      infections.

PMID- 22470842
TI  - III-V/Si hybrid photonic devices by direct fusion bonding.
AB  - Monolithic integration of III-V compound semiconductors on silicon is highly
      sought after for high-speed, low-power-consumption silicon photonics and low
      cost, light-weight photovoltaics. Here we present a GaAs/Si direct fusion bonding
      technique to provide highly conductive and transparent heterojunctions by
      heterointerfacial band engineering in relation to doping concentrations. Metal-
      and oxide-free GaAs/Si ohmic heterojunctions have been formed at 300 degrees C;
      sufficiently low to inhibit active material degradation. We have demonstrated 1.3
      MUm InAs/GaAs quantum dot lasers on Si substrates with the lowest threshold
      current density of any laser on Si to date, and AlGaAs/Si dual-junction solar
      cells, by p-GaAs/p-Si and p-GaAs/n-Si bonding, respectively. Our direct
      semiconductor bonding technique opens up a new pathway for realizing ultrahigh
      efficiency multijunction solar cells with ideal bandgap combinations that are
      free from lattice-match restrictions required in conventional heteroepitaxy, as
      well as enabling the creation of novel high performance and practical
      optoelectronic devices by III-V/Si hybrid integration.

PMID- 22470841
TI  - Fracturing ranked surfaces.
AB  - Discretized landscapes can be mapped onto ranked surfaces, where every element
      (site or bond) has a unique rank associated with its corresponding relative
      height. By sequentially allocating these elements according to their ranks and
      systematically preventing the occupation of bridges, namely elements that, if
      occupied, would provide global connectivity, we disclose that bridges hide a new
      tricritical point at an occupation fraction p = p(c), where p(c) is the
      percolation threshold of random percolation. For any value of p in the interval
      p(c) < p <= 1, our results show that the set of bridges has a fractal dimension
      d(BB) ~ 1.22 in two dimensions. In the limit p -> 1, a self-similar fracture is
      revealed as a singly connected line that divides the system in two domains. We
      then unveil how several seemingly unrelated physical models tumble into the same
      universality class and also present results for higher dimensions.

PMID- 22470843
TI  - Factors affecting response rates to mailed preoperative surveys among
      arthroplasty patients.
AB  - AIM: To identify factors that affect patient response rates to preoperative
      functional surveys in hip and knee arthroplasty patients. METHODS: From May 2008
      to March 2009, 247 patients were scheduled more than 4 wk in advance for hip or
      knee arthroplasty by one of two participating surgeons at our center. A
      personalized questionnaire comprised of the Short Form 12 (SF-12) and Western
      Ontario and McMaster Universities (WOMAC) Index was mailed to patients at random
      time points ranging from 7 to 101 d prior to surgery. Nine independent factors
      were documented prospectively, including age, gender, ethnicity, marital status,
      type of surgery, surgeon, days prior to surgery (DPS) of survey mailing, WOMAC
      score and SF-12 score. The date of the completed survey receipt was also
      documented. For non-responders, the surveys were completed with the research team
      at the hospital upon admission. Multivariate regression and chi(2) analysis were
      performed with Statistical Analysis Software software. RESULTS: DPS was the only
      factor that affected patient response. Mailing surveys 26 d to 31 d prior to
      surgery dates led to a peak response rate of 80% that was significantly higher (P
      < 0.023) than response rates for patients who were mailed their surveys <= 16 d
      (62.5%), 17 d to 25 d (70%) or >= 32 d prior to surgery (55%). No other factors,
      including preoperative WOMAC and SF-12 scores, significantly influenced response
      behavior. CONCLUSION: The DPS was independently the most significant predictor of
      response rates for pre-operative functional data among patients scheduled for hip
      and knee arthroplasty.

PMID- 22470844
TI  - Analyses of possible risk factors for subacromial impingement syndrome.
AB  - AIM: To evaluate the association between various risk factors, including sleeping
      position, and impingement syndrome. Impingement syndrome is the most common cause
      of shoulder problems. The pathogenesis of this problem is still debated these
      days. METHODS: This was a case control study conducted at the outpatient clinic
      of Songklanakarind hospital. Data regarding history, physical examination and
      radiographic evaluations using supraspinatous outlet views were obtained from all
      patients with clinically suspected impingement syndrome. The diagnoses of
      impingement syndrome were confirmed by a xylocaine subacromial injection test.
      All patients were interviewed concerning their usual sleeping position, which was
      categorized into supine, decubitus, prone and undetermined. Radiographs were
      evaluated to determine the shape of the acromion, which was divided into 3 types:
      flat, curved and hook. We used logistic regression analysis to determine the
      association between risk factors and outcome. RESULTS: The study group included
      111 patients with impingement syndrome and 191 healthy volunteers as a control
      group. The mean age was about 50 years with a body mass index (BMI) of 24 kg/m(2)
      in both groups. The most common shape of the acromion was flat (84.5%), followed
      by curved (10.7%) and hook (4.8%). We found the 4 independent risk factors
      affecting impingement syndrome were smoking status, occupation, acromion shape
      and sleeping position. Patients who currently smoked had a 6.8 times greater risk
      of impingement syndrome compared to non-smokers (OR 6.8, 95% CI: 1.2-39) and
      government officers had a 6.3 times increased risk compared to rubber tappers (OR
      6.3, 95% CI: 1.3-30.3). Patients with a hook type acromion had 6.2 times the risk
      of flat type (OR 6.2, 95% CI: 1.1-35) and patients who slept in the decubitus
      position had 3.7 times the risk of those who slept in the supine position (OR
      3.7, 95% CI: 1.2-11.6). No significant associations were found between age, sex,
      BMI, sports activity and impingement syndrome. CONCLUSION: Independent risk
      factors affecting impingement syndrome are current smoker, government officer, a
      hook-type acromion and the decubitus sleeping position.

PMID- 22470846
TI  - Measurement of forces generated during distraction of growing-rods in early onset
      scoliosis.
AB  - AIM: To measure the forces applied during distraction of growing-rods in early
      onset scoliosis (EOS), aimed at developing a motorized elongation device.
      METHODS: A consecutive series of measurements were carried out to analyze the
      forces applied by the surgeon during distraction of single growing-rods in 10
      patients affected by EOS (mean age 8.3 years; range 6 to 10 years) undergoing the
      first distraction 6 months following implantation of the rods. For each
      measurement, output from the transducer of a dedicated pair of distraction
      calipers was recorded at zero load status and at every 1 mm of distraction, up to
      a maximum of 12 mm for each of the two connected rods. RESULTS: Twenty
      measurements were obtained showing a linear increase of the load with increasing
      distraction, with a mean peak force of 485 N at 12 mm distraction and a single
      reading over 500 N. We did not observe bone fractures or ligament disruptions
      during or after rod elongations. There was one case of superficial wound
      infection in the cohort. CONCLUSION: The safe peak force carrying capacity of a
      motorized device for distraction of growing-rods is 500N.

PMID- 22470845
TI  - Innervation of cervical ventral facet joint capsule: Histological evidence.
AB  - AIM: To assess the presence of nerves in ventral facet joint capsules as facet
      capsules are generally implicated in neck pain. METHODS: Twenty-four ventral
      cervical facet joint capsules were harvested from 3 unembalmed cadavers. Paraffin
      sections from these capsules were processed to identify neurofilament and
      substance P immunoreactive fibers. Nerve fiber presence was also verified by a
      silver impregnation method. RESULTS: Neurofilament reactive fibers were observed
      in sections from 9 capsules. They were observed in areas with collagen fibers and
      areas with irregular connective tissue. Substance P reactive nerve fibers were
      found in sections from 7 capsules in similar areas. Silver impregnation also
      revealed the presence of nerve fibers. The nerve fibers were also found as
      bundles in the lateral margins of the capsule. A Pacinian corpuscle-like ending
      was also observed in one specimen. CONCLUSION: Nerve fibers revealed by
      neurofilament immunoreactivity and silver staining support innervation of the
      ventral aspect of the facet joint capsule. The presence of substance P reactive
      fibers supports the potential role of these elements in mediating pain. The
      presence of a Pacinian-like ending implicates a potential role in joint movement.

PMID- 22470847
TI  - Metabolic syndrome leading to chronic kidney disease: An emerging threat.

PMID- 22470848
TI  - Renal endocrinology: The new frontier.

PMID- 22470849
TI  - The sun, the moon, and renal endocrinology.

PMID- 22470850
TI  - Reno-endocrinal disorders: A basic understanding of the molecular genetics.
AB  - The successful management of endocrine diseases is greatly helped by the complete
      understanding of the underlying pathology. The knowledge about the molecular
      genetics contributes immensely in the appropriate identification of the causative
      factors of the diseases and their subsequent management. The fields of nephrology
      and endocrinology are also interrelated to a large extent. Besides performing the
      secretory functions, the renal tissue also acts as target organ for many hormones
      such as antidiuretic hormone (ADH), atrial natriuretic peptides (ANP), and
      aldosterone. Understanding the molecular genetics of these hormones is important
      because the therapeutic interventions in many of these conditions is related to
      shared renal and endocrine functions, including the anemia of renal disease,
      chronic kidney disease, mineral bone disorders, and hypertension related to
      chronic kidney disease. Their understanding and in-depth knowledge is very
      essential in designing and formulating the therapeutic plans and innovating new
      management strategies. However, we still have to go a long way in order to
      completely understand the various confounding causative relationships between the
      pathology and disease of these reno-endocrinal manifestations.

PMID- 22470851
TI  - Rickets-vitamin D deficiency and dependency.
AB  - Rickets is an important problem even in countries with adequate sun exposure. The
      causes of rickets/osteomalacia are varied and include nutritional deficiency,
      especially poor dietary intake of vitamin D and calcium. Non-nutritional causes
      include hypophosphatemic rickets primarily due to renal phosphate losses and
      rickets due to renal tubular acidosis. In addition, some varieties are due to
      inherited defects in vitamin D metabolism and are called vitamin D dependent
      rickets. This chapter highlights rickets/osteomalacia related to vitamin D
      deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic
      rickets and rickets due to renal tubular acidosis are discussed in other sections
      of the journal.

PMID- 22470852
TI  - Hypophosphatemic rickets.
AB  - Hypophosphatemic rickets is a disorder of bone mineralization caused due to
      defects (inherited/acquired) in the renal handling of phosphorus. This group
      includes varied conditions, X-linked hypophosphatemic rickets being the most
      common inheritable form of rickets. The other common forms are autosomal dominant
      hypophosphatemic rickets and tumor-induced osteomalacia. Although these
      conditions exhibit different etiologies, increased phosphatonins form a common
      link among them. Fibroblast growth factor 23 (FGF23) is the most widely studied
      phosphatonin. Genetic studies tend to show that the phosphorus homeostasis
      depends on a complex osteo-renal axis, whose mechanisms have been poorly
      understood so far. Newer disorders are being added as the mechanisms in this axis
      get discovered. This review focuses on the clinical, biochemical, genetic
      features and management of hypophosphatemic disorders leading to defective
      mineralization.

PMID- 22470853
TI  - Vasopressin receptor antagonists and their role in clinical medicine.
AB  - Hyponatremia is the most common electrolyte abnormality in hospitalized patients.
      Its treatment is based not only on extracellular fluid volume status of patients
      but also on its pathogenetic mechanisms. Conventional treatment of hyponatremia
      like fluid restriction, which is useful in euvolemic and hypervolemic
      hyponatremia, has very poor patient compliance over long term. Vasopressin
      receptor antagonists (Vaptans) are a new group of nonpeptide drugs which have
      been used in various clinical conditions with limited success. Whereas conivaptan
      is to be administered intravenously, the other vaptans like tolvaptan,
      lixivaptan, and satavaptan are effective as oral medication. They produce
      aquaresis by their action on vasopressin type 2 (V2R) receptors in the collecting
      duct and thus increase solute free water excretion. Vaptans are being used as an
      alternative to fluid restriction in euvolemic and hypervolemic hyponatremic
      patients. Efficacy of vaptans is now well accepted for management of correction
      of hyponatremia over a short period. However, its efficacy in improving the long
      term morbidity and mortality in patients with chronic hyponatremia due to
      cirrhosis and heart failure is yet to be established. Vaptans have not become the
      mainstay treatment of hyponatremia yet.

PMID- 22470854
TI  - The reno-pineal axis: A novel role for melatonin.
AB  - The pineal gland is a tiny endocrine gland whose physiologic role has been the
      focus of much research and much more speculation over the past century. This mini
      review discusses recent findings which correlate melatonin and renal physiology,
      and postulates the presence of a "reno-pineal axis." Drawing lessons from
      comparative endocrinology, while quoting human data, it advocates the need to
      study the "reno-pineal axis" in greater detail.

PMID- 22470855
TI  - Growth hormone in chronic renal disease.
AB  - Severe growth retardation (below the third percentile for height) is seen in up
      to one-third children with chronic kidney disease. It is thought to be
      multifactorial and despite optimal medical therapy most children are unable to
      reach their normal height. Under-nutrition, anemia, vitamin D deficiency with
      secondary hyperparathyroidism, metabolic acidosis, hyperphosphatemia, renal
      osteodystrophy; abnormalities in the growth hormone/insulin like growth factor
      system and sex steroids, all have been implicated in the pathogenesis of growth
      failure. Therapy includes optimization of nutritional and metabolic
      abnormalities. Failure to achieve adequate height despite 3-6 months of optimal
      medical measures mandates the use of recombinant GH (rGH) therapy, which has
      shown to result in catch-up growth, anywhere from 2 cm to 10 cm with satisfactory
      liner, somatic and psychological development.

PMID- 22470857
TI  - Sexual and gonadal dysfunction in chronic kidney disease: Pathophysiology.
AB  - Sexual and gonadal dysfunction/infertility are quite common in patients with
      chronic kidney disease. Forty percent of male and 55% of female dialysis patients
      do not achieve orgasm. The pathophysiology of gonadal dysfunction is
      multifactorial. It is usually a combination of psychological, physiological, and
      other comorbid factors. Erectile dysfunction in males is mainly due to arterial
      factors, venous leakage, psychological factors, neurogenic factors, endocrine
      factors, and drugs. Sexual dysfunction in females is mainly due to hormonal
      factors and manifests mainly as menstrual irregularities, amenorrhea, lack of
      vaginal lubrication, and failure to conceive. Treatment of gonadal dysfunction in
      chronic kidney disease is multipronged and an exact understanding of underlying
      pathology is essential in proper management of these patients.

PMID- 22470856
TI  - Interactions between thyroid disorders and kidney disease.
AB  - There are several interactions between thyroid and kidney functions in each other
      organ's disease states. Thyroid hormones affect renal development and physiology.
      Thyroid hormones have pre-renal and intrinsic renal effects by which they
      increase the renal blood flow and the glomerular filtration rate (GFR).
      Hypothyroidism is associated with reduced GFR and hyperthyroidism results in
      increased GFR as well as increased renin - angiotensin - aldosterone activation.
      Chronic kidney disease (CKD) is characterized by a low T3 syndrome which is now
      considered a part of an atypical nonthyroidal illness. CKD patients also have
      increased incidence of primary hypothyroidism and subclinical hypothyroidism. The
      physiological benefits of a hypothyroid state in CKD, and the risk of CKD
      progression with hyperthyroidism emphasize on a conservative approach in the
      treatment of thyroid hormone abnormalities in CKD. Thyroid dysfunction is also
      associated with glomerulonephritis often by a common autoimmune etiology. Several
      drugs could affect both thyroid and kidney functions. There are few described
      interactions between thyroid and renal malignancies. A detailed knowledge of all
      these interactions is important for both the nephrologists and endocrinologists
      for optimal management of the patient.

PMID- 22470858
TI  - Erythropoietin use and abuse.
AB  - Recombinant human erythropoietin (rhEPO) is arguably the most successful
      therapeutic application of recombinant DNA technology till date. It was isolated
      in 1977 and the gene decoded in 1985. Since then, it has found varied
      applications, especially in stimulating erythropoiesis in anemia due to chronic
      conditions like renal failure, myelodysplasia, infections like HIV, in
      prematurity, and in reducing peri-operative blood transfusions. The discovery of
      erythropoietin receptor (EPO-R) and its presence in non-erythroid cells has led
      to several areas of research. Various types of rhEPO are commercially available
      today with different dosage schedules and modes of delivery. Their efficacy in
      stimulating erythropoiesis is dose dependent and differs according to the
      patient's disease and nutritional status. EPO should be used carefully according
      to guidelines as unsolicited use can result in serious adverse effects. Because
      of its capacity to improve oxygenation, it has been abused by athletes
      participating in endurance sports and detecting this has proved to be a
      challenge.

PMID- 22470860
TI  - Medical management of renal stone.
AB  - Kidney stone is a common clinical problem faced by clinicians. The prevalence of
      the disease is increasing worldwide. As the affected population is getting
      younger and recurrence rates are high, dietary modifications, lifestyle changes,
      and medical management are essential. Patients with recurrent stone disease need
      careful evaluation for underlying metabolic disorder. Medical management should
      be used judiciously in all patients with kidney stones, with appropriate
      individualization. This chapter focuses on medical management of kidney stones.

PMID- 22470859
TI  - Nephrolithiasis: Endocrine evaluation.
AB  - Nephrolithias is a common problem in populations around the world, and contribute
      significantly to the development of end stage renal disease. It is a matter of
      debate whether the metabolic factors responsible for renal stone formation are
      similar or variable in different populations around the globe. This review
      discusses the influence of different metabolic and dietary factor, and some other
      co-morbid conditions on the etiopathogenesis Nephrolithiasis. Evaluation and
      medical management of Nephrolithiasis is summarized in the later part of the
      article.

PMID- 22470861
TI  - LIPITENSION: Interplay between dyslipidemia and hypertension.
AB  - The burden of cardiovascular disease (CVD) is increasing worldwide. The increase
      in the burden is a major concern in developing countries like India. It is well
      established that hypertension and dyslipidemia are the two major contributing
      risk factors for CVD. Various epidemiological studies have shown the prevalence
      of the co-existence of hypertension and dyslipidemia, in the range of 15 to 31%.
      The co-existence of the two risk factors has more than an additive adverse impact
      on the vascular endothelium, which results in enhanced atherosclerosis, leading
      to CVD. This review emphasizes on the 'co-existence and interplay of dyslipidemia
      and hypertension'. The authors have termed the co-existence as, 'LIPITENSION'.
      The term LIPITENSION may help clinicians in easy identification and aggressive
      management of the two conditions together, ultimately preventing future
      cardiovascular events.

PMID- 22470862
TI  - Protein energy wasting in chronic kidney disease: An update with focus on
      nutritional interventions to improve outcomes.
AB  - Protein-energy wasting (PEW) is common in patients with chronic kidney disease
      (CKD). PEW is one of the strongest predictors of mortality in patients with CKD.
      The International Society of Renal Nutrition and Metabolism (ISRNM) expert panel
      has defined PEW as a, "state of decreased body stores of protein and energy fuels
      (body protein and fat masses)". The ISRNM panel has also proposed diagnostic
      criteria of PEW with four categories. Cachexia is a severe form of PEW. The
      proposed causes of PEW are multi-factorial and include nutritional and non
      nutritional mechanisms. The literature indicates that PEW can be mitigated or
      corrected with an appropriate diet and enteral nutritional support that targets
      dietary protein intake. Dietary requirements and enteral nutritional support must
      also be considered in patients with CKD and diabetes mellitus and in children
      with CKD, in addition to dialysis patients. Features of ideal dietary supplement
      have also been discussed. Dietary interventions such as enteral feeding with high
      protein meals or supplements might improve the nutritional status and outcomes in
      dialysis patients.

PMID- 22470863
TI  - Renal endocrine manifestations during polytrauma: A cause of concern for the
      anesthesiologist.
AB  - Nowadays, an increasing number of patients get admitted with polytrauma, mainly
      due to road traffic accidents. These polytrauma victims may exhibit associated
      renal injuries, in addition to bone injuries and injuries to other visceral
      organs. Nevertheless, even in cases of polytrauma, renal tissue is
      hyperfunctional as part of the normal protective responses of the body to
      external insults. Both polytrauma and renal injuries exhibit widespread renal,
      endocrine, and metabolic responses. The situation is very challenging for the
      attending anesthesiologist, as he is expected to contribute immensely, not only
      in the resuscitation of such patients, but if required, to allow the operative
      procedures in case of life-threatening injuries. During administration of
      anesthesia, care has to be taken, not only to maintain hemodynamic stability, but
      equal attention has to be paid to various renal protection strategies. At the
      same time, various renoendocrine manifestations have to be taken into account, so
      that a judicious use of anesthesia drugs can be made, to minimize the renal
      insults.

PMID- 22470864
TI  - Renal manifestations of primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHPT) is associated with nephrolithiasis and
      nephrocalcinosis. Hypercalciuria is one of the multiple factors that is
      implicated in the complex pathophysiology of stone formation. The presence of a
      renal stone (symptomatic or asymptomatic) categorizes PHPT as symptomatic and is
      an indication for parathyroid adenomectomy. Progression of nephrocalcinosis is
      largely reversible after successful surgery, but the residual risk persists. PHPT
      is also associated with declining renal function. In case of asymptomatic mild
      PHPT, annual renal functional assessment is advised. Guidelines suggest that an
      estimated glomerular filtration rate (eGFR) < 60 ml / minute / 1.73 m(2) is an
      indication for parathyroid adenomectomy. This article discusses how to monitor
      and manage renal stones and other related renal parameters in case of PHPT.

PMID- 22470865
TI  - Vitamin D deficiency in children living in Jeddah, Saudi Arabia.
AB  - OBJECTIVE: Vitamin D deficiency is an unrecognized epidemic and a common health
      problem worldwide. This study was conducted to evaluate the vitamin D status in
      children living in Jeddah, Saudi Arabia and to study its relation to various
      variables. MATERIALS AND METHODS: A cross-sectional study was conducted in the
      pediatric clinic in Jeddah Clinic Hospital-Kandarah, Jeddah, KSA, from October
      through December 2010, in which 510 healthy children aged 4-15 years were
      enrolled. Serum calcium, phosphorus, alkaline phosphatase and 25-hydroxyvitamin D
      [25(OH)D] were measured. Dietary vitamin D intake and duration of daily sunlight
      exposure were determined. 25(OH)D levels <20 ng/mL and <7 ng/mL were defined as
      relative and severe vitamin D deficiency, respectively. RESULTS: The mean
      concentration of 25(OH)D was 13.07 +/- 7.81 ng/mL. Seventy subjects (13.72%) had
      normal 25(OH)D level ranging 20-70 ng/mL. Three hundred (58.82%) had relative
      25(OH)D deficiency and 140 (27.45%) had severe deficiency (P=0.000). 220 (43.14%)
      subjects were males and 290 (56.86%) were females having a statistically
      significant higher incidence of 25(OH)D deficiency (P=0.019). 54.9% were Saudis,
      27.45% were Yemenis and 11.76% were Egyptians. Saudis and Yemenis were more
      subjected to 25(OH)D deficiency in comparison to Egyptians and other
      nationalities (P=0.01). There were significant inverse correlations between
      25(OH)D levels and bony aches (P=0.000). 56.25% of asymptomatic children had
      vitamin D deficiency (P=0.000). Duration of sunlight exposure and daily intake of
      vitamin D had significant effects on serum level of vitamin D (P=0.000).
      CONCLUSIONS: A high prevalence of vitamin D deficiency in children living in
      Jeddah was observed in this study. Vitamin D supplementation of food products can
      prevent vitamin D deficiency in these children.

PMID- 22470866
TI  - Vitamin D deficiency in hemodialysis patients.
AB  - BACKGROUND: Vitamin D [(25(OH)D] deficiency and insufficiency is common in
      patients with chronic kidney disease (CKD). 25(OH)D has been found to have
      beneficial effects on bone, cardiovascular and immune functions. There are little
      data about vitamin D levels in Indian patients on dialysis. This study was
      undertaken to determine the vitamin D status of Indian CKD patients on
      hemodialysis. MATERIALS AND METHODS: We included 45 patients on maintenance
      hemodialysis coming to Medanta, Medicity, Gurgaon. 25(OH)D levels were measured
      with radioimmunoassay (Diasorin) method and parathyroid hormone (PTH) was
      measured using electrochemiluminiscence immunoassay (ECLIA). RESULTS: The mean
      age of patients was 55 +/- 13 years. 32/45 (71%) were males. 23/45 (51%) were
      diabetics. The median duration of hemodialysis was 5.5 months (range 1-74
      months). 33/45 (74%) patients were on thrice weekly hemodialysis. The mean level
      of vitamin D was 10.14 +/- 8.7 ng/ml. Majority of the patients [43/45 (95.5%)]
      were either vitamin D deficient or had insufficient levels. 40/45 (88.9%) were
      vitamin D deficient (levels <20 ng/ml); of these, 29/40 (64.4%) had severe
      vitamin D deficiency (levels <10 ng/ml) and 3/45 (6.7%) had insufficient levels
      (20-30 ng/ml) of vitamin D. Only 2/45 (4.4%) patients had normal levels of
      vitamin D. 23/45 (51%) of patients were receiving calcitriol. The mean levels of
      serum calcium, phosphorus, alkaline phosphatase, and albumin were 8.8 +/- 0.64
      mg/dl, 5.0 +/- 0.7 mg/dl, 126 +/- 10.3 IU/l and 3.6 +/- 0.62 g/dl, respectively.
      PTH levels ranged from 37 to 1066 pg/ml, and the median was 195.8 pg/ml. There
      was a weak correlation between 25(OH)D levels and weight, sex, hemoglobin,
      albumin, alkaline phosphatase, and presence of diabetes. There was, however, no
      correlation with duration of dialysis or PTH levels. CONCLUSION: Vitamin D
      deficiency and insufficiency are universal in our hemodialysis patients, with
      severe vitamin D deficiency in two-third of patients.

PMID- 22470867
TI  - Prevalence of vitamin D deficiency in post renal transplant patients.
AB  - AIM: Deficiency of Vitamin D is prevalent in the general population, especially
      in Chronic Kidney Disease (CKD) patients. The exact prevalence of Vitamin D
      deficiency is unknown in post renal transplant recipients. The classical and non
      classical effects of vitamin D deficiency are complicated by the use of steroids
      and calcineurin inhibitors (CNIs) in the renal transplant population. The aim of
      this study is to document the prevalence of Vitamin D deficiency in the post
      renal transplant population. MATERIALS AND METHODS: A total of 51 renal
      transplant recipients under follow-up at Indraprastha Apollo Hospital, between
      June 2009 and March 2011, were enrolled in this study. Parathormone (PTH), 25(OH)
      vitaminD3, calcium, and phosphate levels were determined in all the patients. The
      patients were then classified into different groups based on the severity of the
      Vitamin D deficiency, time since transplantation, and level of graft function.
      RESULTS: Overall, four patients (8%) were vitamin D sufficient, 17 patients (33%)
      insufficient, 26 patients (51%) mildly deficient, and four (8%) severely
      deficient. The degree of deficiency did not differ with reference to the time
      since transplant or level of graft function. Sixty-nine percent had high PTH
      level, 22% were normal, and 9% had a low parathyroid hormone level. There was an
      inverse correlation between Vitamin D deficiency and serum PTH level. CONCLUSION:
      In this study, there was a high prevalence of vitamin D deficiency in renal
      transplant recipients. This did not get corrected, despite nutritional
      improvement or normalization of the glomerular filtration rate (GFR) post
      transplantation. Therefore, the study emphasizes routine evaluation and proper
      supplementation of Vitamin D in all post renal transplant patients.

PMID- 22470868
TI  - Pattern of urinary albumin excretion in normotensive young and adolescent Indian
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a clinically heterogeneous
      endocrine disorder affecting up to 4-8% of women of reproductive age. The aim of
      this study was to evaluate the presence of microalbuminuria in women with PCOS
      and study its correlation with the various metabolic, clinical, and hormonal
      parameters. MATERIALS AND METHODS: A cross-sectional study involving 69 PCOS
      women was carried out in a tertiary care center hospital. The diagnosis of PCOS
      was made according to the Rotterdam criteria. Blood samples were collected in the
      follicular phase of the menstrual cycle and analyzed for fasting luteinizing
      hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17
      hydroxyprogesterone (17-OHP), total testosterone (T), glucose, insulin, and lipid
      profile. Urinary albumin was measured in the first void spot urine sample.
      RESULTS: The mean age of the subjects was 22.0 +/- 4.1 years and 21.8 +/- 4.7
      years in normoalbuminuric and microalbuminuric groups, respectively. Urinary
      albumin excretion (UAE) varied from 5 mg/l to 100 mg/ml, with a median of 5 mg/l.
      Microalbuminuria was observed in 17/69 (24.6%) of subjects. The mean UAE was 3.65
      +/- 4.44 mg/l in the normoalbuminuria group versus 45.29 +/- 22.74 mg/l in the
      microalbuminuria group. Upon univariate analysis, hip circumference, diastolic
      blood pressure, and fasting blood glucose showed significant correlations with
      urinary albumin concentration (r = 0.264, 0.264, and 0.551, respectively; P =
      0.028, 0.029, and 0.000, respectively). No association between UAE and the usual
      cardiovascular risk factors could be found upon regression analysis. CONCLUSION:
      About 24.6% of women with PCOS showed presence of microalbuminuria in the first
      void spot urine sample. Screening for the presence of microalbuminuria can help
      in early identification of a subset of PCOS women with a high risk for future
      CVD, who can be subjected to preventive strategies at the earliest. However,
      further studies are needed before recommending routine use of UAE in PCOS cases
      for the detection of CVD risk.

PMID- 22470869
TI  - Protocol-based metabolic evaluation in high-risk patients with renal stones in
      North India.
AB  - CONTEXT: Renal calculus disease has a lifetime recurrence rate of 80%. Protocol
      based metabolic evaluation in high-risk subjects for recurrent renal stones
      reveals abnormalities in a large subset of subjects. However, such information is
      not available in Indian subjects. AIMS: To evaluate the abnormalities by a
      protocol-based metabolic evaluation in patients at a high risk for recurrent
      renal stones. SETTINGS AND DESIGN: Prospective, academic tertiary care center.
      MATERIALS AND METHODS: Fifty North Indian patients (38 males and 12 females; mean
      age 38 +/- 10.2 years) with recurrent or bilateral renal stones were evaluated.
      All subjects underwent a protocol-based evaluation involving estimation of serum
      total calcium, phosphorus, creatinine, albumin, iPTH, 25(OH)D(3),
      1,25(OH)(2)D(3), and a calcium load test. Estimation of daily urinary excretion
      of volume, oxalate, calcium, uric acid, and citrate, and urinary acidification
      studies were performed. STATISTICAL ANALYSIS USED: Descriptive statistics and t
      test. RESULTS: An underlying disorder was detected in 48 (96%) patients. Almost
      half had two or more metabolic abnormalities. The metabolic abnormalities
      detected were: Hypercalciuria 26 (52%) patients, renal hypercalciuria 16 (32%),
      absorptive hypercalciuria 6 (12%), unclassified hypercalciuria 4 (8%),
      hyperoxaluria 27 (54%), hyperuricosuria 9 (18%), distal renal tubular acidosis 4
      (8%; 2 complete and 2 partial), primary hyperparathyroidism 3 (6%), and
      hypocitraturia 14 (n=18, 77%). In two patients, the etiology could not be
      detected. CONCLUSIONS: Protocol-based metabolic evaluation reveals metabolic
      abnormalities in majority of patients with nephrolithiasis. The spectrums of
      metabolic abnormalities are different in Indian subjects as compared to the
      western population.

PMID- 22470870
TI  - A descriptive study of hyponatremia in a tertiary care hospital of Eastern India.
AB  - BACKGROUND: Hyponatremia is one of the commonest electrolyte disturbances
      encountered in medical wards and contributes to substantial morbidity and
      mortality. However, early recognition and management drastically alters
      prognosis. Therefore, this observational study was taken up to explore the
      clinical profile of hyponatremia. AIM: To assess the incidence and clinical
      profile of hyponatremia in medically ill patients. MATERIALS AND METHODS: This
      observational study was conducted in the medical ward of a tertiary care hospital
      from March 2010 to April 2011. All patients underwent routine hemogram, blood
      biochemistry, serum electrolytes, thyroid function tests, and morning serum
      cortisol estimation. This was followed by a plasma and urinary osmolality
      determination (osmometer 800 CL) as well as urinary sodium estimation. Patients
      were diagnosed to have syndrome of inappropriate antidiuretic hormone secretion
      (SIADH) if they satisfied the Bartter and Schwartz criteria. RESULTS: 201
      patients (16.4%) had a serum Na < 135 meq/l. There were 126 (62.69%) male
      patients and 75 (37.31%) female patients. Severe hyponatremia (Na < 120 meq/l)
      was detected in 30 patients (2.4%). The largest group of hyponatremic patients
      were euvolemic [102 (50.74%)], followed by hypervolemic [54 (26.86%)] and
      hypovolemic [45 (22.4%)]. Sixty-six patients fulfilled the criteria for SIADH.
      The most common underlying predisposing factor for hyponatremia in our case
      series was fluid loss by vomiting/diarrhea. During the hospital stay, 13.5%
      (15/201) hyponatremic patients died, while the corresponding figure in
      normonatremic patients was 8.5% (87/1020). CONCLUSION: The incidence of
      hyponatremia in our series was higher than values mostly reported in western
      literature. Euvolemic hyponatremia was the most common type, a significant
      fraction of which is SIADH.

PMID- 22470871
TI  - Hunches on hunchbacks.
AB  - The hunchback has long been a symbol of revilement in art and literature. This
      write up tries to find the cause of the deformity into two iconic hunchbacks in
      literature, Manthara and Quasimodo.

PMID- 22470872
TI  - Vitamin D toxicity.
AB  - A 67-year-old female was admitted to the hospital with a history of lethargy,
      memory impairment, confusion, anorexia and gait imbalance for 2 weeks duration.
      She did not have any history of fall or head injury. She had total hip
      replacement 1 year back and was on orthopedic follow-up. Magnetic resonance
      imaging (MRI) on admission revealed no focal abnormalities. Routine biochemistry
      detected hypercalcemia, and she was treated with I/V fluid, diuretics and
      glucocorticoids. She was screened thoroughly to exclude occult malignancy. After
      7 days of admission, a follow-up orthopedic prescription revealed that she was
      getting inj. Arachitol 6 lac units every week for last 3 months. On the 9(th) day
      of admission, she was detected to have very high serum 25(OH) vitamin D level
      (254.70 ng/ml). Patient was discharged after 2 weeks after her serum calcium came
      down to normal range with the advice of no dietary calcium and vitamin D intake.
      Her 25(OH) vitamin D level remained high for the next 6 months. Now she is
      completely asymptomatic and her serum 25(OH) D is normal.

PMID- 22470873
TI  - Gitelman's syndrome with panhypopituitarism: Reno-endocrine interplay.
AB  - Gitelman's syndrome is an inherited tubulopathy affecting thiazide-sensitive
      sodium chloride cotransporter, which manifests with hypokalemic alkalosis,
      hypomagnesemia, and hypocalciuria. Recently few cases have been described having
      an association of Gitelman's syndrome with pituitary abnormalities on imaging,
      though with normal hormonal status. We describe the first case of an adult
      patient having Gitelman's syndrome and hypopituitarism with abnormal pituitary
      imaging. She presented to us with hypotension, hypokalemia, hypomagnesemia with
      alkalosis, hypothyroidism, hypocortisolism, and hypogonadism. She was treated
      with replacement of electrolytes and hormones, to which she showed an excellent
      response.

PMID- 22470874
TI  - Status epilepticus as the only presentation of the neonatal Bartter syndrome.
AB  - Bartter syndrome is a rare hereditary (autosomal recessive) salt-losing
      tubulopathy characterized by hypokalemia, hypochloremia, metabolic alkalosis, and
      normal blood pressure with hyperreninemia, The underlying renal abnormality
      results in excessive urinary losses of sodium, chloride, and potassium. We report
      a case of a four-month-old infant with neonatal Bartter syndrome, who presented
      only with status epilepticus. To the best of our present knowledge, there is no
      reported case of Bartter syndrome who presented with status epilepticus.

PMID- 22470875
TI  - Conservative management of emphysematous pyelonephritis.
AB  - Emphysematous pyelonephritis, though uncommon, is a severe necrotizing kidney
      infection common in patients with diabetes. Surgical treatment has been advocated
      as the treatment of choice in most of the patients. We present the clinical
      course of an elderly lady who presented with emphysematous pyelonephritis and was
      successfully managed with medical treatment despite the presence of adverse
      prognostic factors like acute renal failure and thrombocytopenia.

PMID- 22470876
TI  - Acute renal failure: A rare presentation of Sheehan's syndrome.
AB  - Sheehan's syndrome occurs as a result of ischemic pituitary necrosis secondary to
      severe postpartum bleeding. It is one of the most common causes of
      hypopituitarism, characterized by variable clinical presentation. Acute kidney
      injury occurs rarely in Sheehan's syndrome and most of the cases have been found
      to be precipitated by rhabdomyolysis. We here present a case of Sheehan's
      syndrome with acute kidney injury where theprecipitating cause was chronic
      hypocortisolemia. We believe this is the first reported case of Sheehan's
      syndrome in which acute kidney injury was precipitated by adrenal insufficiency.

PMID- 22470877
TI  - Brown tumor in mandible as a first sign of vitamin D deficiency: A rare case
      report and review.
AB  - Central giant cell granulomas (CGCGs) are uncommon but the most aggressive benign
      intraosseous tumors of jaws, with an unpredictable outcome. They account for less
      than 7% of all benign jaw lesions, with a female to male ratio of about 2:1. The
      classical "brown tumor" is commonly seen in the long bones, pelvis, and ribs.
      Facial bone involvement is rare and usually appears as solitary or multilocular
      soap bubble like radiolucencies. CGCGs are traditionally treated by both surgical
      and intralesional injection, with a variable recurrence rate. Here, we report a
      12-year-old female patient with mandibular brown tumor as a first sign of
      secondary hyperthyroidism induced due to vitamin D deficiency and hypocalcemia.

PMID- 22470878
TI  - Endocrinology in the hills of Himachal Pradesh, India.

PMID- 22470879
TI  - Posterior encephalopathy: An uncommon manifestation of calcium toxicity.

PMID- 22470880
TI  - Acute stridor and wheeze as an initial manifestation of hypocalcemia in an
      infant.

PMID- 22470881
TI  - Coexistence of pituitary macroadenoma with systemic lupus erythematosus and
      antiphospholipid syndrome.

PMID- 22470882
TI  - Sheehan's syndrome: Presented with hyponatremia and hypoglycemia after 14 years
      from delivery.

PMID- 22470883
TI  - Ramadan fasting in patients with type 2 diabetes mellitus: Experience from a
      teaching hospital.

PMID- 22470884
TI  - Prescribing gliptins: Enthusiasm should be coupled with caution.

PMID- 22470885
TI  - Journal of advanced pharmaceutical technology and research.

PMID- 22470886
TI  - Drug discovery: Past and present.

PMID- 22470887
TI  - Electronic tongue: An analytical gustatory tool.
AB  - Taste is an important organoleptic property governing acceptance of products for
      administration through mouth. But majority of drugs available are bitter in
      taste. For patient acceptability and compliance, bitter taste drugs are masked by
      adding several flavoring agents. Thus, taste assessment is one important quality
      control parameter for evaluating taste-masked formulations. The primary method
      for the taste measurement of drug substances and formulations is by human
      panelists. The use of sensory panelists is very difficult and problematic in
      industry and this is due to the potential toxicity of drugs and subjectivity of
      taste panelists, problems in recruiting taste panelists, motivation and panel
      maintenance are significantly difficult when working with unpleasant products.
      Furthermore, Food and Drug Administration (FDA)-unapproved molecules cannot be
      tested. Therefore, analytical taste-sensing multichannel sensory system called as
      electronic tongue (e-tongue or artificial tongue) which can assess taste have
      been replacing the sensory panelists. Thus, e-tongue includes benefits like
      reducing reliance on human panel. The present review focuses on the
      electrochemical concepts in instrumentation, performance qualification of E
      tongue, and applications in various fields.

PMID- 22470888
TI  - Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery.
AB  - Periodontal pockets act as a natural reservoir filled with gingival crevicular
      fluid for the controlled release delivery of antimicrobials directly. This
      article reflects the present status of nonsurgical controlled local intrapocket
      delivery of antimicrobials in the treatment of periodontitis. These sites have
      specialty in terms of anatomy, permeability, and their ability to retain a
      delivery system for a desired length of time. A number of antimicrobial products
      and the composition of the delivery systems, its use, clinical results, and their
      release are summarized. The goal in using an intrapocket device for the delivery
      of an antimicrobial agent is the achievement and maintenance of therapeutic drug
      concentration for the desired period of time. Novel controlled drug delivery
      system are capable of improving patient compliance as well as therapeutic
      efficacy with precise control of the rate by which a particular drug dosage is
      released from a delivery system without the need for frequent administration.
      These are considered superior drug delivery system because of low cost, greater
      stability, non-toxicity, biocompatibility, non-immunogenicity, and are
      biodegradable in nature. This review also focus on the importance and ideal
      features of periodontal pockets as a drug delivery platform for designing a
      suitable dosage form along with its potential advantage and limitations. The
      microbes in the periodontal pocket could destroy periodontal tissues, and a
      complete knowledge of these as well as an ideal treatment strategy could be
      helpful in treating this disease.

PMID- 22470890
TI  - Technological study of preparing gel from semi-solid extract of Cacalia hastata
      L.
AB  - Most of the drugs which are used for wound healing are imported in Mongolia. It
      is required to develop drug formulation and increase local productions used for
      the treatment of wound healing. For the purpose of solving the above problems, we
      aimed to prepare new drug formulation from Cacalia hastata L. for the treatment
      of wound healing. Cacalia hastata L. is a medicinal plant, member of the family
      Asteraceae. Cacalia hastata L. is widely used for the Mongolian traditional
      medicine to treat wound healing, gastric ulcer, poisoning fever, liver fever,
      bile fever, oral cavity, and gynecological diseases. We prepared Cacalia gel from
      semi-solid extract of Cacalia hastata L. using various excipients such as gel
      former, solvent, neutralizer, antimicrobial preservative, and humectant. Gel
      formulation was standardized by such criteria, as the amount of biologically
      active compound, appearance (color, smell), pH, viscosity, and bacterial
      contamination. Stability testing of gel formulation was studied by long-term
      method. The quality of the Cacalia gel which was stored in room temperature, its
      appearance, viscosity, and amount of biological active compound were stable. The
      stability testing of the gel formulation from Cacalia hastata L. is continued.

PMID- 22470889
TI  - Dietary-induced cancer prevention: An expanding research arena of emerging diet
      related to healthcare system.
AB  - Diet plays a vital role in the management of cancer because they are the source
      of important physiologically functional components. Scientific observations
      support the idea that dietary supplement can prevent breast cancer recurrences.
      Strong correlations are established between the high intake of saturated fat and
      the incidence of different types of cancer. It is found that chronic alcohol
      consumption is associated with increased risk of cancers of oral cavity, pharynx,
      esophagus, and larynx. Again, some evidences are also found regarding
      phosphorous, glutamate level in the body, and incidence of cancer. Different
      physiologically functional components are found in the dietary materials. Fibers,
      the major dietary components, have long been recognized for the unique properties
      in the treatment of cancer, which are related to its antineoplastic functions.
      Antioxidant rich diet has been added to the list of cancer-preventing dietary
      components. Also, recently published research has shown that natural carotenoids
      in the diet leads to a normalization of body epithelial cells and protects
      against the risk of stomach and esophagus cancer, and improves the immune
      system's response. Again, fruit juices, processed vegetable juices, orange peel,
      green tea, vitamins, flavonoids, and trace materials have cancer inhibitory
      properties. Clearly, there has been increasing recognition of chemoprotective
      functions. Now, it can be recognized for another kind of functionality for the
      improvement of the health of mankind.

PMID- 22470891
TI  - Response surface methodology and process optimization of sustained release
      pellets using Taguchi orthogonal array design and central composite design.
AB  - Furosemide is a powerful diuretic and antihypertensive drug which has low
      bioavailability due to hepatic first pass metabolism and has a short half-life of
      2 hours. To overcome the above drawback, the present study was carried out to
      formulate and evaluate sustained release (SR) pellets of furosemide for oral
      administration prepared by extrusion/spheronization. Drug Coat L-100 was used
      within the pellet core along with microcrystalline cellulose as the diluent and
      concentration of selected binder was optimized to be 1.2%. The formulation was
      prepared with drug to polymer ratio 1:3. It was optimized using Design of
      Experiments by employing a 3(2) central composite design that was used to
      systematically optimize the process parameters combined with response surface
      methodology. Dissolution studies were carried out with USP apparatus Type I
      (basket type) in both simulated gastric and intestinal pH. The statistical
      technique, i.e., the two-tailed paired t test and one-way ANOVA of in vitro data
      has proposed that there was very significant (P<=0.05) difference in dissolution
      profile of furosemide SR pellets when compared with pure drug and commercial
      product. Validation of the process optimization study indicated an extremely high
      degree of prognostic ability. The study effectively undertook the development of
      optimized process parameters of pelletization of furosemide pellets with
      tremendous SR characteristics.

PMID- 22470892
TI  - Effect of different solvent extracts of Benincasa hispida T. on experimental
      hypochlorhydria in rat.
AB  - Hypochlorhydria is a common problem in any age of people like other gastric
      disorders. It has so many etiologies such as sympathetic dominance, antiseretory
      drug use, excess sugar and refined foods, etc. In the present study, our
      objective was to search out the effective solvent extract of fruit of Benincasa
      hispida T. for the management of hypochlorhydria in model male albino rats.
      Hypochlorhydria was induced in rat as per standard method by oral administration
      of ranitidine. Different solvent extracts (Hydro-methanol, ethyl acetate, and
      aqueous) of ripe fruit of B. hispida were prepared following the standard
      protocol. Various parameters in this concern like free acidity, total acidity,
      pH, pepsin concentration, chloride and vitamin C levels in gastric juice were
      measured by standard biochemical and titrimetric methods. It was found that pre
      administration followed by co-administration of aqueous extract of B. hispida
      (ABH) resulted significant correction of ranitidine-induced hypochlorhydria in
      rat. This aqueous extract-treated group showed increased levels of vitamin C,
      pepsin, and chloride concentration in gastric juice as well as the antioxidant
      status significantly (P<0.05) in respect to other extract-treated groups. From
      the results, it can be concluded that the ABH has most effective anti
      hypochlorhydric and antioxidative efficacy than other solvent extracts of said
      plant fruit.

PMID- 22470893
TI  - Hypoglycemic activity of Cassia javanica Linn. in normal and streptozotocin
      induced diabetic rats.
AB  - In present work, one of the ornamentals and medicinally less known plant Cassia
      javanica has been explored for hypoglycemic potential. It aimed to check the
      hypoglycemic effect of C. javanica leaves on normal and streptozotocin (STZ)
      induced diabetic rats by acute and sub-acute studies. Prior to the hypoglycemic
      study, acute oral toxicity testing of drug was performed. Later, the effects of
      single and multiple doses of test drug were studied using various parameters.
      Dried powdered leaf material was used as an oral drug. The preliminary
      phytochemistry of drug was done by standard qualitative tests. Diabetes was
      induced in rats by single intraperitoneal injection of STZ. Single and multiple
      doses of test drug (0.5 g/kg body weight/day) were given to normal and diabetic
      rats. The parameters studied were blood glucose, serum cholesterol, serum
      triglycerides, and serum proteins. The results of test drug were compared with
      standard hypoglycemic drug-glibenclamide (0.01 g/kg/day). Statistical analysis
      was done by 'Student's 't' test' and one way ANOVA test. In preliminary
      phytochemistry, antidiabetic compounds were detected. Unlike acute, subacute
      treatment of test drug showed highly significant reduction (37.62%) in blood
      glucose level of diabetic rats in ten days. This effect was considerably good in
      comparison with standard drug (63.51%). The test drug and standard drug exhibited
      insignificant change in the abnormal levels of serum metabolites of diabetic
      rats. Preclinically, C. javanica was proved to be effective hypoglycemic agent.

PMID- 22470894
TI  - Antidiabetic effect of a black mangrove species Aegiceras corniculatum in alloxan
      induced diabetic rats.
AB  - Earlier ethnopharmacological records divulged the traditional usages of mangrove
      Aegiceras corniculatum (Linn.) Blanco distributed in coastal and estuarine areas
      of Southeast India. Excluding scientific knowledge of A. corniculatum against
      diabetes an upgrowing endocrinal disorder, our present study evaluated the effect
      on alloxan-induced diabetic rats. Diabetes was induced in adult rats of the
      Wistar strain by intraperitoneal injection of alloxan monohydrate. The
      experimental rats were administered with leaf suspension of A. corniculatum post
      orally using an intragastric tube. On completion of the 60-day treatment, a range
      of biochemical parameters were tested including liver hexokinase, glucose
      6phosphatase and fructose 1, 6 bisphosphatase in the liver of control and allaxon
      diabetic rats. As a result, A. corniculatum leaf suspension showed moderate
      reduction in blood glucose (from 382 +/- 34 to 105 +/- 35), glycosylated
      hemoglobin, a decrease in the activities of glucose-6 phosphatase and fructose 1,
      6-bisphosphatase, and an increase activity of liver hexokinase achieved through
      the oral administration of extract on 100 mg/kg. The present findings support
      promising results in terms of antidiabetic activities establishing its candidacy
      for further purification of individual compound in order to understand their
      mechanism of action.

PMID- 22470895
TI  - Design, synthesis, and antimicrobial screening of novel pyridyl-2-amidrazone
      incorporated isatin mannich bases.
AB  - Isatin is an endogenous compound and reported to possess a wide range of
      biological activities. Numerous papers have shown that the pyridyl-2-amidrazone
      nucleus possesses a potent antimicrobial activity. Based on these prior
      observations, we postulated that a compound containing both isatin and pyridyl-2
      amidrazone pharmacophores could be very effective for antimicrobial activity.
      Unfavorable adsorption, distribution, metabolism, and excretion (ADME) properties
      can in many cases lead to the clinical trials failure of potentially successful
      drug candidates. Their evaluation, therefore, at an earlier stage is desired.
      Here, we also present the predicted ADME properties of our ligands through
      computation. All the compounds (2a(1-5)) exhibited a better solubility,
      diffusion, Log P, molecular weight, etc., with no violations making the ligands
      pharmacodynamically active and better oral absorptive series. Based on the
      results of computational design, a series of novel pyridyl-2-amidrazone
      incorporated isatin Mannich bases were synthesized and screened for their
      antimicrobial activities. IR, (1)H-NMR, and Mass Spectroscopy data were
      consistent with the assigned structures. The results exhibited that all of the
      lead compounds showed good antimicrobial activities; noticeably, the compound
      2a(2) showed the best activity against Candida albicans (16 MUg/ml) and compound
      2a(3) was found to be the most active derivative against Staphylococcus aureus
      and Escherichia coli at minimal inhibitory concentration values of 4 and 32
      MUg/ml, respectively.

PMID- 22470896
TI  - Incidence of adverse drug reactions in human immune deficiency virus-positive
      patients using highly active antiretroviral therapy.
AB  - To estimate the incidence of adverse drug reactions (ADRs) in Human immune
      deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART).
      To identify the risk factors associated with ADRs in HIV patients. To analyze
      reported ADRs based on various parameters like causality, severity,
      predictability, and preventability. Retrospective case-control study. An 18-month
      retrospective case-control study of 208 patients newly registered in ART center,
      RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART.
      Predictability was calculated based on the history of previous exposure to drug.
      Multivariate logistic regressions were used to identify the risk factors for
      ADRs. Data were analyzed using the chi-square test for estimating the correlation
      between ADRs and different variables. All statistical calculations were performed
      using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active
      Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin
      rash and anemia were the most commonly observed ADRs. The organ system commonly
      affected by ADR was skin and appendages (31.57%). The ADRs that were moderate
      were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine +
      Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/MUl were
      80.28%, male gender were observed to be the risk factors for ADRs. Our study
      finding showed that there is a need of active pharmaceutical care with intensive
      monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male
      and female gender, with CD4 count <=250 cells/mm(3) with comorbid conditions.

PMID- 22470897
TI  - Chitosan-alginate microcapsules of amoxicillin for gastric stability and
      mucoadhesion.
AB  - Amoxicillin-loaded microcapsules were prepared by ionotropic gelation of sodium
      alginate (ALG) with chitosan (CS) in presence of calcium chloride as
      gastroretentive delivery system. The effect of pH, concentration of ALG, CS and
      calcium chloride, and drug : ALG ratio were optimized in this study for
      minimizing the degradation of drug in acidic environment and increasing the
      loading efficacy and mucoadhesive efficiency of microcapsules. The optimum
      condition for prepared CS-ALG microcapsules was 2%w/v ALG, 0.75%w/v CS (pH5.0),
      and 1.0% w/v calcium chloride. The resulting microcapsules had drug entrapment
      efficiency of 84% and average size of 840 mm. CS concentration significantly
      influenced particle size and encapsulation efficiency of CS-ALG microcapsules
      (P<0.05). Decrease in the drug: ALG ratio resulted in an increased release of
      amoxicillin in acidic media. The relative decomposition of drug after
      encapsulation in CS-ALG microcapsules was decreased to 20.7%, 41.9%, and 83.3% in
      2, 4, and 8 hours, respectively.

PMID- 22470898
TI  - Use of minocycline as systemic antimicrobial therapy in refractory periodontitis
      with chronic gingival enlargement.
AB  - Periodontal disease is a multifactorial disease having various risk factors, but
      a dynamic interaction between bacterial products and host response in association
      with genetic and environmental factors is considered as the primary cause for
      periodontal tissue destruction in periodontitis. This bacterial-host interaction
      which is ever-so-present in periodontitis directs us toward utilizing
      antimicrobial agents along with the routine mechanical debridement. This case
      report present a case of a female patient with recurrent periodontal infections
      with gingival enlargement treated with systemic Minocycline in conjunction with
      the conventional non-surgical approach.

PMID- 22470899
TI  - The impact of policy and screening on cervical cancer in England.
AB  - There has been a significant statistical decrease in the incidence of cervical
      cancer since screening programmes have been introduced. This article will explore
      and evaluate the impact of the Cancer Reform Strategy on cervical screening in
      England, which preceded the Government's policy for cancer care announced in
      January 2011. The Strategy raised the initial age of screening from 20 to 25
      years of age. This left a group of the population who could not access screening
      while also not being eligible for vaccines against cervical cancer. Although this
      caused concern for many people, the media coverage and reaction to the human
      papilloma virus (HPV) vaccine and the death of Jade Goody, for example,
      encouraged women to consider cervical screening. The barriers to screening have
      been identified but overall the Cancer Reform Strategy was found have a positive
      impact both economically and socially. The Strategy has led the way for the
      Government's policy for cancer care, which needs to continue achieving the same
      positive outcomes.

PMID- 22470900
TI  - National chemotherapy skills passport: a step closer.

PMID- 22470901
TI  - A snapshot of innovation: chemotherapy delivery in the UK.
AB  - Chemotherapy is a major part of NHS care. Aroud 200 hospitals deliver
      chemotherapy services within their facilities, in community clinics and in the
      patients' homes. The safety of such services has attracted attention resulting in
      the production of a service template for the future by the National Chemotherapy
      Advisory Board in 2009. Its report recognized opportunities for redesigning
      services and recommended optimising the development of non-medical staff. The UK
      chemotherapy partnership was established to help professionals involved in
      chemotherapy share their experiences of improving and developing services and
      roles. This short article places the need for the UK Chemotherapy Partnership
      website in context and describes the origins of the Partnership as well as future
      plans.

PMID- 22470902
TI  - Treating chronic myeloid leukaemia: NICE guidance.
AB  - Chronic myeloid leukaemia (CML) affects approximately 560 people annually in the
      UK. Although median age at diagnosis is 60 years (National Institute for Health
      and Clinical Excellence (NICE), 2012), CML occurs in all age groups (National
      Comprehensive Cancer Network (NCCN), 2012). It is a clonal myeloproliferative
      disorder which is characterized by a reciprocal translocation between chromosomes
      9 and 22, resulting in the formation of the Philadelphia chromosome (Ph
      Chromosome) and the development of an unregulated tyrosine kinase (BCR-ABL) which
      is responsible for the pathogenesis of CML (NCCN, 2012).

PMID- 22470903
TI  - An overview of drug development for metastatic breast cancer.
AB  - The prevalence of breast cancer is increasing as more women are living with the
      disease. Outcomes have improved as a result of progress in all major aspects of
      multidisciplinary care. These include surgery, radiotherapy, hormonal therapy,
      chemotherapy and newer targeted drugs. Two aspects merit particular attention
      here. First, there is an understanding now that cancer is a heterogenous disease
      and a 'one-size-fits-all' approach is becoming redundant, albeit slowly. Second,
      basic science and an appreciation of cellular molecular targets in those
      different types of breast cancer is being translated into the clinic and has led
      to the development of exciting new drugs for both triple negative and HER2
      positive relapsed disease. An improved understanding of endocrine resistance
      remains an unmet need in drug development and here, it appears worthwhile to
      adopt less conventional approaches. Better trial design with a focus on
      biomarkers should lower barriers to regulatory approval as well as increase cost
      effectiveness.

PMID- 22470904
TI  - Advanced prostate cancer: treatment and patient-centred care.
AB  - There have been many significant advances in the treatment of prostate cancer,
      yet it remains a growing problem for men's health. Many men die from prostate
      cancer each year and many more live with non-cancerous, but debilitating,
      prostate disorders. This article discusses advanced (metastatic) prostate cancer,
      provides nurses with an overview of treatment options available to men with this
      condition, and offers a starting point from which to examine further evidence. It
      aims to encourage nurses to ensure that the patient is involved in making any
      decisions that could potentially impact on his health and wellbeing. In line with
      current thinking, the patient must be at the heart of every decision and be
      provided with greater choice and control (Department of Health, 2010).

PMID- 22470905
TI  - NAPNAP position statement on continuing education.

PMID- 22470906
TI  - NAPNAP position statement on access to care.

PMID- 22470907
TI  - Bloom where you are planted.

PMID- 22470908
TI  - The importance of transcultural nursing in cancer care.
AB  - All patients around the time of cancer diagnosis are emotionally vulnerable. This
      sense of anxiety is further heightened for patients who are not fully integrated
      into the society in which they are receiving care because of the cultural shock
      and language barriers they may face. This article explores the author's
      experience of caring for a patient from China who was studying in the UK and was
      admitted with acute promyelocytic leukaemia. The patient had a limited grasp of
      English and was used to very different cultural norms. Bridging the cultural gap
      as outlined by Narayanasamy in the ACCESS model (2002) enabled the author to
      provide the important holistic nursing care that could be easily overlooked in
      these situations. There is a need for nurses to actively seek to understand
      cultural differences and take the opportunity to experience transcultural
      nursing.

PMID- 22470909
TI  - Guest editors' introduction: Special section on ACM VRST 2010.

PMID- 22470910
TI  - Though times call for unified cancer services and care.

PMID- 22470911
TI  - [FRET (Fluorescence Resonance Energy Transfer) for the determination of minimal
      inhibitory concentration of antibiotics].

PMID- 22470913
TI  - [Tuberculosis glossary].

PMID- 22470912
TI  - [Experimental vaccination against tuberculosis].

PMID- 22470914
TI  - [Not just a success story. On the history of tuberculosis treatment].

PMID- 22470915
TI  - [A resistant organism fight with modern weapons. Biology of mycobacteria and new
      molecular targets].

PMID- 22470916
TI  - [Appearance varied, complex diagnostics. Clinical aspects of tuberculosis].

PMID- 22470917
TI  - [Accidental discoveries, different mechanisms of action. Active agents against
      Mycobacterium tuberculosis in clinical application].

PMID- 22470918
TI  - [Better search strategies, hopeful candidates. The search for new
      antimycobacterial drugs].

PMID- 22470919
TI  - [Coinfection as a challenge of the health system. TB / HIV / AIDS - prevention
      and treatment in Ghana].

PMID- 22470920
TI  - [Old and new anti-mycobacterial drugs. Fatty acid synthesis as a target].

PMID- 22470922
TI  - [Are there any treatment options? Resistance imported from Russia].

PMID- 22470921
TI  - Recombinant factor VIIa analog (vatreptacog alfa [activated])  for treatment of
      joint bleeds in hemophilia patients with  inhibitors: a randomized controlled
      trial.
AB  - BACKGROUND: A recombinant factor VIIa analog (NN1731; vatreptacog alfa
      [activated]) was developed to provide safe, rapid and sustained resolution of
      bleeds in patients with hemophilia and inhibitors. PATIENTS/METHODS: This global,
      prospective, randomized, double-blinded, active-controlled, dose-escalation trial
      evaluated and compared one to three doses of vatreptacog alfa at 5, 10, 20, 40,
      and 80 lg kg(-1) with one to three doses of recombinant FVIIa (rFVIIa) at 90 lg
      kg(-1) in the treatment of acute joint bleeds in hemophilia patients with
      inhibitors. The primary endpoint comprised adverse events; secondary endpoints
      were evaluations of immunogenicity, pharmacokinetics, and efficacy. RESULTS AND
      CONCLUSIONS: Overall, 96 joint bleeds in 51 patients (> 12 years of age) were
      dosed. Vatreptacog alfa was well tolerated, with a low frequency of adverse
      events. No immunogenic or thrombotic events related to vatreptacog alfa were
      reported. A high efficacy rate of vatreptacog alfa in controlling acute joint
      bleeds was observed; 98% of bleeds were controlled within 9 h of the initial dose
      in a combined evaluation of 20-80 lg kg(-1) vatreptacog alfa. The efficacy rate
      observed for rFVIIa (90%) is consistent with data from published clinical trials.
      The trial was not powered to compare efficacy, and further trials are needed to
      investigate the efficacy of vatreptacog alfa as compared with that of rFVIIa. The
      trial was registered at ClinicalTrials.gov ( REGISTRATION NUMBER: NCT00486278).

PMID- 22470923
TI  - [A reasonable and cost-effective strategy? Routine TB screening of immigrants].

PMID- 22470924
TI  - [A new clinical disease entity. Tuberculosis in users of TNF-alpha inhibitors].

PMID- 22470925
TI  - Recommendations for developing uniform laboratory  monitoring of heparinoid
      anticoagulants in children.

PMID- 22470926
TI  - UK announces strategy for regenerative medicine.

PMID- 22470927
TI  - Central American leaders debate drug decriminalisation.

PMID- 22470928
TI  - South Africa rolls out pilot health insurance scheme.

PMID- 22470929
TI  - Controversy continues over safety of bisphenol A.

PMID- 22470930
TI  - Where all the ladders start.

PMID- 22470931
TI  - 20th-Century "medical Marco Polos" in the origins of preventive cardiology and
      cardiovascular disease epidemiology.
AB  - In mid-20th century, several streams of knowledge converged to create the new
      academic discipline of cardiovascular disease epidemiology and the new practice
      of preventive cardiology. One stream was modern cardiology, with the ability to
      diagnose myocardial infarction, to characterize and count its victims, and to
      report vital statistics on cardiovascular causes of death. Another stream came
      from burgeoning clinical and laboratory research and greater understanding of the
      underlying processes of atherosclerosis and hypertension. A third stream came
      from the observations of intellectually curious "medical Marco Polos," who
      brought back from travels their tales of unusual population frequencies of heart
      attacks, along with ideas about sociocultural causes. This led to more formal
      research about cardiovascular disease risk and causes among populations and about
      mechanisms in the clinic and laboratory. The broad river of investigation thus
      formed produced a risk paradigm of the multiple biologic, behavioral, and
      societal factors in causal pathways to the common cardiovascular diseases. An
      evidence base was built for sound clinical and public health approaches to
      prevention. Here, the author tells brief stories about 5 early and particularly
      observant world travelers and their influence on knowledge and thinking about
      prevention.

PMID- 22470932
TI  - Long-term follow-up and course of life in children with constipation.

PMID- 22470933
TI  - Sports for disabled people: a general outlook.

PMID- 22470934
TI  - Detection of >=1Mb microdeletions and microduplications in a single cell using
      custom oligonucleotide arrays.
AB  - OBJECTIVE: High resolution detection of genomic copy number abnormalities in a
      single cell is relevant to preimplantation genetic diagnosis and potentially to
      noninvasive prenatal diagnosis. Our objective is to develop a reliable array
      comparative genomic hybridization (CGH) platform to detect genomic imbalances as
      small as ~1Mb ina single cell. METHODS: We empirically optimized the conditions
      for oligonucleotide-based array CGH using single cells from multiple
      lymphoblastoid cell lines with known copy number abnormalities. To improve
      resolution, we designed custom arrays with high density probes covering
      clinically relevant genomic regions. RESULTS: The detection of megabase-sized
      copy number variations (CNVs) in a single cell was influenced by the number of
      probes clustered in the interrogated region. Using our custom array, we
      reproducibly detected multiple chromosome abnormalities including trisomy 21, a
      1.2Mb Williams syndrome deletion, and a 1.3Mb CMT1A duplication. Replicate
      analyses yielded consistent results. CONCLUSION: Aneuploidy and genomic
      imbalances with CNVs as small as 1.2Mb in a single cell are detectable by array
      CGH using arrays with high-density coverage in the targeted regions. This
      approach has the potential to be applied for preimplantation genetic diagnosis to
      detect aneuploidy and common microdeletion/duplication syndromes and for
      noninvasive prenatal diagnosis if single fetal cells can be isolated.

PMID- 22470935
TI  - Douala prenatal diagnosis staff (Cameroon): four years of activity.

PMID- 22470936
TI  - [Guidelines of the French Society of Hypertension: blood pressure measurements in
      the diagnosis and monitoring of hypertensive patients].

PMID- 22470937
TI  - Cell lineage and cis-regulation for a unique GABAergic/glycinergic neuron type in
      the larval nerve cord of the ascidian Ciona intestinalis.
AB  - The tunicate Ciona intestinalis larva has a simple central nervous system (CNS),
      consisting of fewer than 400 cells, which is homologous to the vertebrate CNS.
      Recent studies have revealed neuronal types and networks in the larval CNS of C.
      intestinalis, yet their cell lineage and the molecular mechanism by which
      particular types of neurons are specified and differentiate remain poorly
      understood. Here, we report cell lineage origin and a cis-regulatory module for
      the anterior caudal inhibitory neurons (ACINs), a putative component of the
      central pattern generator regulating swimming locomotion. The vesicular GABA/
      glycine transporter gene Ci-VGAT, a specific marker for GABAergic / glycinergic
      neurons, is expressed in distinct sets of neurons, including ACINs of the tail
      nerve cord and others in the brain vesicle and motor ganglion. Comparative
      genomics analysis between C. intestinalis and Ciona savignyi and functional
      analysis in vivo identified the cis-regulatory module responsible for Ci-VGAT
      expression in ACINs. Our cell lineage analyses inferred that ACINs derive from
      A11.116 cells, which have been thought to solely give rise to glial ependymal
      cells of the lateral wall of the nerve cord. The present findings will provide a
      solid basis for future studies addressing the molecular mechanism underlying
      specification of ACINs, which play a critical role in controlling larval
      locomotion

PMID- 22470938
TI  - Distinct mechanisms control the timing of differentiation of two myeloid
      populations in Xenopus ventral blood islands.
AB  - Previous study has suggested that distinct populations of myeloid cells exist in
      the anterior ventral blood islands (aVBI) and posterior ventral blood islands
      (pVBI) in Xenopus neurula embryo. However, details for differentiation programs
      of these two populations have not been elucidated. In the present study, we
      examined the role of Wnt, vascular endothelial growth factor (VEGF) and
      fibroblast growth factor signals in the regulation of myeloid cell
      differentiation in the dorsal marginal zone and ventral marginal zone explants
      that are the sources of myeloid cells in the aVBI and pVBI. We found that
      regulation of Wnt activity is essential for the differentiation of myeloid cells
      in the aVBI but is not required for the differentiation of myeloid cells in the
      pVBI. Endogenous activity of the VEGF signal is necessary for differentiation of
      myeloid cells in the pVBI but is not involved in the differentiation of myeloid
      cells in the aVBI. Overall results reveal that distinct mechanisms are involved
      in the myeloid, erythroid and endothelial cell differentiation in the aVBI and
      pVBI.

PMID- 22470939
TI  - Do quality indicators lead to over-intervention?

PMID- 22470940
TI  - Surgical checklists come to ambulatory centers.

PMID- 22470941
TI  - CMS tests hospital infection survey.

PMID- 22470942
TI  - Spreading the gospel of QI one person at a time.

PMID- 22470943
TI  - Prenatal initiative yields safety improvements.

PMID- 22470944
TI  - Med rec initiative achieves 95% compliance.

PMID- 22470945
TI  - Three pharmacy safety problems solved.

PMID- 22470946
TI  - [To meet challenges and focus on main problems to promote the study of
      occupational stress].

PMID- 22470947
TI  - [Study on mental workload of teachers in primary schools].
AB  - OBJECTIVE: To investigate the distribution characteristics and influencing
      factors of mental workload of teachers in primary schools. METHODS: National
      Aeronautics and Space Administration-Task Load Index (NASA-TLX) was used to
      assess the mental workload levels for 397 teachers of primary schools in a city.
      RESULTS: The mental workload (64.34+10.56) of female teachers was significantly
      higher than that (61.73+ 9.77) of male teachers (P<0.05). The mental workload
      (65.66+10.42) of "-35" years old group was the highest. When age of teachers was
      younger than 35 years old, there was a positive correlation between the mental
      workload and age (r=0.146, P<0.05). When age of teachers was older than 35 years
      old, there was a negative correlation between the mental workload and age (r=
      0.190, P<0.05). The teachers with higher education level felt higher mental
      workload (unstandardized coefficients B=1.524, standardized coefficients /=0.111,
      P<0.05). There was a positive correlation between the mental workload and working
      hours per day (unstandardized coefficients B =4.659, standardized coefficients/3
      =0.223, P<0.001). CONCLUSION: Mental workload of the teachers in primary schools
      is closely related to age, educational level and work hours per day. Work hours
      per day is an important risk factor for mental workload. Reducing work hours per
      day (8 hours) is an effective measure of alleviating the mental workload of
      teachers in primary schools.

PMID- 22470948
TI  - [Occupational health surveillance for the workers at high temperature in a
      industrial zone].

PMID- 22470949
TI  - [Effects of the workplace violence on the sub-health status of nurses].
AB  - OBJECTIVE: To explore the effects of workplace violence on sub-health status of
      nurses and to provide the theoretical basis for preventing the workplace violence
      in the hospitals and improving the health status of nurses. METHODS: A total of
      679 nurses were selected by using stratified cluster sampling method. The Chinese
      version of workplace violence scale (WVS) and sub-health scale were used to
      measure workplace violence and sub-health status, respectively. RESULTS: The
      subjects with middle age (30-45 years) were found to have the highest incidence
      of physical assault (24.5%) and emotional assault (52.2%) as compared with other
      subjects (P<0.05). The prevalence (23.6%) of emotional assault of subjects with
      lowest education levels was significantly lower than that of others (P<0.05). The
      nurses with work shift were more vulnerable to emotional assault (45.1%) than
      those without work shift (36.8%)(P<0.05). The prevalence of the workplace
      violence of nurses in the psychiatric department and emergency department was
      significantly higher than that of nurses in other departments (P<0.05). The
      results of multivariate analysis showed that workplace violence was an important
      risk factor for sub-health status of nurses when other potential confounding
      factors were taken into account. CONCLUSION: The results of present study showed
      that workplace violence plays an important role in sub-health status of nurses
      after adjusting other potential confounding factors. It is important to develop
      the prevention strategies for reducing the incidence of workplace violence and
      improving the sub-health status of nurses.

PMID- 22470950
TI  - [Investigation of health status of workers exposed to low concentration cadmium
      in a zinc powder factory].
AB  - OBJECTIVE: To explore the health status of workers exposed to Cd at low
      concentration. METHODS: One hundred eighteen workers of zinc powder finishing and
      34 staffs were served as the exposure group and control group, respectively. The
      physical examination, blood cadmium, urinary cadmium, blood lead, urinary 32
      microglobin, urine creatine, chest film, pulmonary function , pure tone teat and
      were detected for all subjects. RESULTS: Twelve air samples from 6 monitoring
      points in workshop were detected, the air Cd concentrations were 0.002-0.015
      mg/m3, which were under the national limit of occupational exposure. In exposure
      group, the rates of exceeding standards of blood Cd and urinary Cd were 65.25%
      and 38.16%, respectively, the rate of exceeding standards of urinary Cd for two
      times was 27.12%, the rate of exceeding standard of urine Cd for two times plus
      the positive urinary 32-microglobin was 2.54 %. In control group, the rates of
      exceeding national standard of blood Cd was 26.47 %, but the values of urinary Cd
      were normal. In exposure group, the rate of exceeding standards of urinary Cd
      increased with the service length. Smoking could enhance the rates of exceeding
      standards of blood Cd and urinary Cd. CONCLUSION: In zinc powder finishing, the
      low-concentration cadmium exposure could cause the occupational cadmium
      poisoning, the comprehensive protection measures can reduce the occupational
      cadmium poisoning. It is suggested that the limits of occupational exposure to
      cadmium should be declined.

PMID- 22470951
TI  - [Study on status of needle-stick and other sharps injuries among healthcare
      workers in a general hospital ].
AB  - OBJECTIVE: To understand the prevalence of hospital healthcare workers (HCWs)
      with needle-stick and other sharps injuries, and to provide the basic data for
      intervention study. METHODS: A retrospective investigation was conducted with
      questionnaires for needle-stick and other sharps injuries from January 1- to
      December 31 of 2009 among 1201 healthcare workers in a general hospital. RESULTS:
      The total number of needle-stick and other sharps injuries among 1201 healthcare
      workers in 2009 was 4320, the number of needle-stick and other sharps injuries
      for each person was 3.58 and the incidence of needle-stick and other sharps
      injuries was 78.85 %. The subjects with the high risk of needle-stick and other
      sharps injuries were from the department of gynecology and obstetrics, surgical
      department, intensive care unit and emergency room, the incidences and the
      average numbers of episodes were 94.67% and 4.51 per person, 93.09% and 4.46 per
      person, 85.44% and 3.08 per person, 76.62 % and 4.55 per person in 2009,
      respectively. The operations resulting in the needle-stick and other sharps
      injuries were the breaking glass preparation (ampoule or vial), withdrawing
      needles, preparing sharp devices and performing an operation, the incidences were
      46.96%, 30.97%, 25.73% and 14.49%, respectively. Needle-stick and other sharps
      injuries were mainly caused by ampoules, winged steel needle, disposable
      syringes, suture needles and scalpels, the incidences were 47.04%, 37.22%,
      31.31%, 17.65% and 7.08%, respectively. CONCLUSION: Healthcare worker are still
      at risk of needle- stick and other sharps injuries, which was related to the
      profession, department, medical manipulation and medical apparatus and
      instruments. Special and comprehensive measurements for preventing the needle
      stick and other sharps injuries should be taken actively.

PMID- 22470953
TI  - [An observation on control and prevention of occupational disease].

PMID- 22470954
TI  - [Effects of 0.2 MPa-hyperbaric air exposure on blood pressure and heart rate in
      healthy adults].

PMID- 22470952
TI  - [Effects of immunosuppressant therapy on cellular immunity function in patients
      with aplastic anemia induced by benzene poisoning].

PMID- 22470955
TI  - [Analysis on occupational health examination of the workers at some enterprises
      in a city from 2008 to 2010].

PMID- 22470956
TI  - [Comparison of the levels of T lymphocyte subsets and immune globulins in the
      peripheral blood of road-menders at the different working times at high altitudes
      of 4300 m].

PMID- 22470957
TI  - Bridging between basic medical science and clinical practice.

PMID- 22470958
TI  - [The role of PKC family in biological effects induced by non-ionizing radiation].

PMID- 22470959
TI  - [Panel study: application in research of air pollution epidemiology].

PMID- 22470960
TI  - Selectivity in phagocytosis and persistence of symbiotic algae in the scyphistoma
      stage of the jellyfish Cassiopeia xamachana.
AB  - We have investigated whether interactions between cell-surface macromolecules
      play a role in cellular recognition leading to specificity in the establishment
      of intracellular symbiosis between dinoflagellates and the polyp (scyphistoma)
      stage of the jellyfish Cassiopeia xamachana. All strains of the symbiotic
      dinoflagellate Symbiodinium microadriaticum were phagocytosed by the endodermal
      cells of the scyphistomae when presented to them as cells freshly isolated from
      their respective hosts. The rates of phagocytosis of such cells were high, and
      were directly correlated with the presence of a membrane, thought to be the host
      cell vacuolar membrane that surrounds the freshly isolated algae. Cultured algae
      lack this membrane. All cultured algae, even those that proliferate in host
      tissues, were phagocytosed at very low or undetectable rates. Freshly isolated
      algae treated with reagents that removed the host membrane were phagocytosed at
      low rates. The endodermal cells of the scyphistomae of the non-symbiotic medusa
      Aurelia aurita also phagocytosed freshly isolated algae, but did not phagocytose
      cultured algae. Phagocytosis of algae and carmine particles was found to be a
      competitive process in scyphistomae of C. xamachana. No correlation was observed
      between the surface electrical charge on algae and their phagocytosis by host
      endodermal cells. Neither was there any correlation between phagocytosis and
      persistence. We conclude that the specificity in symbioses between marine
      invertebrates and dinoflagellates appears to be regulated by processes that occur
      after potential algal symbionts are phagocytosed.

PMID- 22470961
TI  - Cellular events in the reestablishment of a symbiosis between a marine
      dinoflagellate and a coelenterate.
AB  - Summary. Within 24 h after the initial phagocytotic uptake of freshly isolated
      (from host tissue) symbiotic algae (Symbiodinium mieroadriaticum) by the
      endodermal cells of the polyp (scyphistoma) stage of the jellyfish Cassiopeia
      xamachana,the algal population was observed to decline despite evidence of algal
      cell division. Analyses of the frequency of phago-lysosome fusion as an indicator
      of possible attempts of the host to digest the algae indicated that,
      althoughphago-lysosome fusion did occur, the low frequency of occurrence is
      inconsistent with the interpretation that the animals digested the algae. Animal
      cell lysosomes were located predominantly at the apices of the endodermal
      cells,and the symbiotic algae were transported toward the bases of the endodermal
      cells.Within 3 days after initial infection, most endodermal cells with algae
      ceased to be phagocytotically active (with respect to the uptake of carmine
      particles). Many of these endodermal cells soon migrated into the mesoglea to
      become what are traditionally referred to as "amoebocytes".Within amoebocytes the
      algae proliferated. The onset of strobilation by the scyphistomae was directly
      correlated with the increase in the algal population within these amoebocytes.

PMID- 22470962
TI  - [Osteoporosis -- a global challenge?].

PMID- 22470963
TI  - The complications of median sternotomy.

PMID- 22470964
TI  - Realizing artificial photosynthesis.
AB  - Artificial photosynthesis comprises the design of systems for converting solar
      energy into useful forms based on the fundamental science underlying natural
      photosynthesis. There are many approaches to this problem. In this report, the
      emphasis is on molecule-based systems for photochemical production of fuels using
      sunlight. A few examples of typical components of artificial photosynthetic
      systems including antennas, reaction centres, catalysts for fuel production and
      water oxidation, and units for photoprotection and photoregulation are presented
      in order to illustrate the current state of the field and point out challenges
      yet to be fully addressed.

PMID- 22470965
TI  - Design principles of photosynthetic light-harvesting.
AB  - Photosynthetic organisms are capable of harvesting solar energy with near unity
      quantum efficiency. Even more impressively, this efficiency can be regulated in
      response to the demands of photosynthetic reactions and the fluctuating light
      levels of natural environments. We discuss the distinctive design principles
      through which photosynthetic light-harvesting functions. These emergent
      properties of photosynthesis appear both within individual pigment-protein
      complexes and in how these complexes integrate to produce a functional, regulated
      apparatus that drives downstream photochemistry. One important property is how
      the strong interactions and resultant quantum coherence, produced by the dense
      packing of photosynthetic pigments, provide a tool to optimize for ultrafast,
      directed energy transfer. We also describe how excess energy is quenched to
      prevent photodamage under high-light conditions, which we investigate through
      theory and experiment. We conclude with comments on the potential of using these
      features to improve solar energy devices.

PMID- 22470966
TI  - Physical constraints on charge transport through bacterial nanowires.
AB  - Extracellular appendages of the dissimilatory metal-reducing bacterium Shewanella
      oneidensis MR-1 were recently shown to sustain currents of 10(10) electrons per
      second over distances of 0.5 microns [El-Naggar et al., Proc. Natl. Acad. Sci. U.
      S. A., 2010, 107, 18127]. However, the identity of the charge localizing sites
      and their organization along the "nanowire" remain unknown. We use theory to
      predict redox cofactor separation distances that would permit charge flow at
      rates of 10(10) electrons per second over 0.5 microns for voltage biases of < or
      = IV, using a steady-state analysis governed by a non-adiabatic electron
      transport mechanism. We find the observed currents necessitate a multi-step
      hopping transport mechanism, with charge localizing sites separated by less than
      1 nm and reorganization energies that rival the lowest known in biology.

PMID- 22470967
TI  - Engineering antiparallel charge-transfer cascades into supramolecular n/p
      heterojunction photosystems: toward directional self-sorting on surfaces.
AB  - This contribution describes recent progress made with the design, synthesis and
      evaluation of supramolecular architectures for artificial photosynthesis.
      Emphasis is on the possible introduction of antiparallel redox gradients into the
      co-axial hole- and electron-transporting channels of supramolecular n/p
      heterojunctions, and on directional, uniform axial and alternate lateral self
      sorting to get there. Recent results suggest that two-component gradients in both
      channels are sufficient for photoinduced charge separation over very long
      distances. Removal of one gradient leads to charge recombination at the usual
      critical distances, inversion of both gradients causes photocurrent inhibition.
      These promising results call for user-friendly, cheap and fast approaches to
      oriented multicomponent architectures on solid surfaces. However, the reduction
      of efforts devoted to covalent organic synthesis will have to be compensated by
      the development of strategic concepts on the supramolecular level to tackle basic
      questions such as self-sorting on surfaces.

PMID- 22470968
TI  - Synthetic polymers for solar harvesting.
AB  - Synthetic polymers incorporating appropriate chromophores can act as light
      harvesting antennae for artificial photosynthetic systems. The photophysical
      processes occurring in a polymer based on phenylene vinylene have been
      investigated at the single chain level and in bulk solution to study energy
      transfer processes. Most single chains of an alternating copolymer of 2-methoxy-5
      (2'-ethylhexyloxy)-1,4-phenylene vinylene and 1,4-phenylene vinylene (alt-co-MEH
      PPV) dispersed in a transparent polymer matrix act as single chromophore emitters
      demonstrating that energy transfer is an efficient process in these polymers.
      However for individual polymer chains there are fluctuations in emission
      intensity ('blinking') and shifts in emission spectra, decay lifetimes and
      emission dipole orientation occurring on a time-scale of tens of seconds.
      Fluorescence blinking also occurs on a sub-millisecond time-scale and follows
      exponential kinetics, whereas the longer blinking is better described by a power
      law. These observations can be interpreted as arising from environmental
      relaxation processes and/or changes in the emitter and demonstrate the wide
      distribution of photophysical behaviours that can be observed among the
      individual molecules of a polymer sample. The relevance of these studies to the
      application of polymer materials for solar harvesting is highlighted.

PMID- 22470969
TI  - Formation of a long-lived electron-transfer state of a naphthalene-quinolinium
      ion dyad and the pi-dimer radical cation.
AB  - An electron donor-quinolinium ion dyad, 2-phenyl-4-(1-naphthyl)quinolinium ion
      (QuPh+-NA), has been synthesized based on a rational design. The X-ray crystal
      structure of QuPh+-NA indicates that the dihedral angle between the NA and QuPh+
      moieties of QuPh+-NA is nearly perpendicular. The one-electron reduction
      potential (E(red)) was observed as a well-defined reversible wave at -0.90 V
      versus SCE. The one-electron reduced species (QuPh*-NA) was detected by ESR. The
      electron self-exchange rate constant (k(ex)) between QuPh+-NA and QuPh*-NA has
      been determined from the ESR linewidth alternation. The reorganization energy
      (lambda) of the electron self-exchange was determined to be 0.42 eV from the
      k(ex) value. Femtosecond laser irradiation of QuPh+-NA at 355 nm results in
      formation of the ET state (QuPh*-NA*+) within 0.5 ps via photoinduced ET from NA
      to the singlet-excited state of QuPh+. The transient absorption bands at 420 nm
      and 700 nm are assigned to the QuPh and NA*+ moieties, respectively. The
      nanosecond laser excitation of QuPh+-NA affords the broad absorption band at 1000
      nm and is due to the pi-dimer radical cation formed between QuPh*-NA*+ and QuPh+
      NA. The intramolecular back electron-transfer process was too slow to compete
      with the intermolecular back electron-transfer reaction judging from the decay
      time profile of QuPh*-NA*+, which obeyed second-order kinetics.

PMID- 22470970
TI  - Development of highly efficient supramolecular CO2 reduction photocatalysts with
      high turnover frequency and durability.
AB  - New Ru(II)-Re(I) supramolecular photocatalysts with a rhenium(I) biscarbonyl
      complex as a catalyst unit were synthesized. They photocatalyzed CO2 reduction to
      CO using a wide-range of visible light, and their photocatalytic abilities were
      strongly affected by the phosphorus ligands on the Re site. Especially, Ru
      Re(FPh), with two P(p-FPh)3 ligands, exhibited tremendous photocatalytic
      properties, i.e. TN(CO) = 207 and phi(CO) = 0.15, and, in addition, this is one
      of the fastest-operating photocatalysts for CO2 reduction to CO, with TF(CO) =
      281 h(-1). We also clarified a balance of transferred electrons in this
      photocatalytic reaction and found that the two electrons necessary for CO
      formation were provided by two sequential reductive quenching processes of the
      excited Ru photosensitizer unit by the reductant BNAH.

PMID- 22470971
TI  - Steric effect for proton, hydrogen-atom, and hydride transfer reactions with
      geometric isomers of NADH-model ruthenium complexes.
AB  - Two isomers, [Ru(1)]2+ (Ru = Ru(bpy)2, bpy = 2,2'-bipyridine, 1 = 2-(pyrid-2'-yl)
      1-azaacridine) and [Ru(2)]2+ (2 = 3-(pyrid-2'-yl)-4-azaacridine), are bioinspired
      model compounds containing the nicotinamide functionality and can serve as
      precursors for the photogeneration of C-H hydrides for studying reactions
      pertinent to the photochemical reduction of metal-C1 complexes and/or carbon
      dioxide. While it has been shown that the structural differences between the
      azaacridine ligands of [Ru(1)]2+ and [Ru(2)]2+ have a significant effect on the
      mechanism of formation of the hydride donors, [Ru(1HH)]2+ and [Ru(2HH)]2+, in
      aqueous solution, we describe the steric implications for proton, net-hydrogen
      atom and net-hydride transfer reactions in this work. Protonation of [Ru(2*-)] in
      aprotic and even protic media is slow compared to that of [Ru(1*-)]+. The net
      hydrogen-atom transfer between *[Ru(1)]2+ and hydroquinone (H2Q) proceeds by one
      step EPT, rather than stepwise electron-proton transfer. Such a reaction was not
      observed for *[Ru(2)]2+ because the non-coordinated N atom is not easily
      available for an interaction with H2Q. Finally, the rate of the net hydride ion
      transfer from [Ru(1HH)]2+ to [Ph3C]+ is significantly slower than that of [Ru
      (2HH)]2+ owing to steric congestion at the donor site.

PMID- 22470972
TI  - How is the water molecule activated on metalloporphyrins? Oxygenation of
      substrates induced through one-photon/two-electron conversion in artificial
      photosynthesis by visible light.
AB  - The reaction mechanism of the highly efficient (phi = 0.60), selective
      photochemical epoxidation of alkenes sensitized by CO-coordinated tetra(2,4,6
      trimethyl)phenylporphyrinatoruthenium(II) (Ru(II)TMP(CO)), with water acting both
      as an electron and oxygen atom donor, was investigated. The steady-state light
      irradiation of the reaction mixture indicated the formation of the Ru(II)TMP (CO)
      cation radical under neutral conditions, which was effectively trapped by an
      hydroxide ion to regenerate the starting sensitizer. By means of a laser flash
      photolysis experiment, the formation of the cation radical as the primary process
      from the triplet excited state of Ru(II)TMP(CO) was clearly observed. Four kinds
      of transients were detected in completely different ranges of the delay time: the
      excited triplet state of Ru(II)TMP(CO) [delay time region <20 micros], the cation
      radical of Ru(II)TMP(CO)(CH3CN) [20-50 micros], the hydroxyl-coordinated
      Intermediate [I] [50-200 micros], and the cyclohexane-attached Intermediate [II]
      [200 micros-8 ms]. A reaction mechanism was revealed that involves RuTMP(CO)
      cation radical formation from the triplet excited state of the sensitizer,
      followed by attack of an hydroxide ion to form an hydroxyl-coordinated Ru
      porphyrin (Intermediate [I]) and subsequent reaction with cyclohexene to form
      Intermediate [II]. The kinetics for each step of the successive processes was
      carefully analyzed and their rate constants were determined. The two-electron
      oxidation of water by one-photon irradiation, as revealed in the photochemical
      epoxidation, is proposed to be one of the more promising candidates to get
      through the bottleneck of water oxidation in artificial photosynthesis.

PMID- 22470973
TI  - Electron transfer kinetics in water splitting dye-sensitized solar cells based on
      core-shell oxide electrodes.
AB  - Photoelectrochemical water splitting occurs in a dye-sensitized solar cell when a
      [Ru(bpy)3]2+-based dye covalently links a porous TiO2 anode film to IrO2 x nH2O
      nanoparticles. The quantum yield for oxygen evolution is low because of rapid
      back electron transfer between TiO2 and the oxidized dye, which occurs on a
      timescale of hundreds of microseconds, When iodide is added as an electron donor,
      the photocurrent increases, confirming that the initial charge injection
      efficiency is high. When the porous TiO2 film is coated with a 1-2 nm thick layer
      of ZrO2 or Nb2O5, both the charge injection rate and back electron transfer rate
      decrease. The efficiency of the cell increases and then decreases with increasing
      film thickness, consistent with the trends in charge injection and recombination
      rates. The current efficiency for oxygen evolution, measured electrochemically in
      a generator-collector geometry, is close to 100%. The factors that lead to
      polarization of the photoanode and possible ways to re-design the system for
      higher efficiency are discussed.

PMID- 22470974
TI  - Light-driven water oxidation with a molecular tetra-cobalt(III) cubane cluster.
AB  - Photoinduced water oxidation to molecular oxygen takes place in systems made of
      [Ru(bpy)3]2+ (bpy = 2,2'-bipyridine) as the photosensitizer, [Co4O4(O2CMe)4(py)4]
      (py = pyridine) as the molecular catalyst and Na2S2O8 as the sacrificial electron
      acceptor. The photochemical quantum yield of the process reaches the outstanding
      value of 30% and depends on pH and catalyst concentration. Transient absorption
      spectroscopy experiments aimed to clarify the first events of the photocatalytic
      process are also reported.

PMID- 22470975
TI  - Colloidal metal oxide particles loaded with synthetic catalysts for solar H2
      production.
AB  - This discussion describes a study of a particulate semiconductor assembly
      consisting of a photoactive ruthenium dye-sensitised metal oxide nanoparticle
      loaded with a synthetic cobaloxime proton reduction catalyst (CoP). The colloidal
      system evolves H2 during visible light illumination in pH neutral aqueous
      solution in the presence of a sacrificial electron donor. The ruthenium
      photosensitiser (RuP) to cobaloxime loading ratio is simple to vary and optimise
      and a range of metal oxide nanoparticles were tested. A maximum photoactivity was
      identified with TiO2 nanoparticles modified with CoP and RuP in a 2: 1 ratio in
      the colloidal reaction mixture: visible light irradiation yielded 600 +/- 32
      micromol H2 h(-1) (g TiO2)(-1). A total turnover number of 108 +/- 9 mol H2 (mol
      CoP)(-1), the evolution of 4340 +/- 240 micromol H2 (g TiO2)(-1) and
      approximately 87 micromol H2 (m2 TiO2)(-1) were observed after 10 h irradiation.
      Linkage of the catalysts to TiO2 is critical for the system to work efficiently,
      and CoP and RuP contain one and two phosphonic acid linker moieties,
      respectively. The novel phosphonate ester analogue of CoP,
      [CoCl(dimethylglyoximato)2(diethyl pyridyl-4-phosphonate)] (1) was also
      synthesised and studied. Complex 1 adsorbs only to a small extent to TiO2 and a
      reduced H2 production rate (182 +/- 8 micromol H2 h(-1) (g TiO2)(-1)) was
      observed when 1 was irradiated with RuP-modified TiO2. Thus, the lower TiO2
      affinity of 1 results in a reduced photoactivity of the dispersion. The described
      semiconductor particles are also presented in the light of being advantageous
      over more established homogenous multi-component systems and supramolecular dyad
      complexes: the reported semi-heterogeneous system is straightforward to assemble
      and it works in a purely aqueous environment.

PMID- 22470976
TI  - A Ga2O3 underlayer as an isomorphic template for ultrathin hematite films toward
      efficient photoelectrochemical water splitting.
AB  - Hematite photoanodes for photoelectrochemical (PEC) water splitting are often
      fabricated as extremely-thin films to minimize charge recombination because of
      the short diffusion lengths of photoexcited carriers. However, poor crystallinity
      caused by structural interaction with a substrate negates the potential of
      ultrathin hematite photoanodes. This study demonstrates that ultrathin Ga2O3
      underlayers, which were deposited on conducting substrates prior to hematite
      layers by atomic layer deposition, served as an isomorphic (corundum-type)
      structural template for ultrathin hematite and improved the photocurrent onset of
      PEC water splitting by 0.2 V. The benefit from Ga2O3 underlayers was most
      pronounced when the thickness of the underlayer was approximately 2 nm. Thinner
      underlayers did not work effectively as a template presumably because of
      insufficient crystallinity of the underlayer, while thicker ones diminished the
      PEC performance of hematite because the underlayer prevented electron injection
      from hematite to a conductive substrate due to the large conduction band offset.
      The enhancement of PEC performance by a Ga2O3 underlayer was more significant for
      thinner hematite layers owing to greater margins for improving the crystallinity
      of ultrathin hematite. It was confirmed that a Ga2O3 underlayer was applicable to
      a rough conducting substrate loaded with Sb-doped SnO2 nanoparticles, improving
      the photocurrent by a factor of 1.4. Accordingly, a Ga2O3 underlayer could push
      forward the development of host-guest-type nanocomposites consisting of highly
      rough substrates and extremely-thin hematite absorbers.

PMID- 22470977
TI  - Accumulative electron transfer: multiple charge separation in artificial
      photosynthesis.
AB  - To achieve artificial photosynthesis it is necessary to couple the single
      electron event of photoinduced charge separation with the multi-electron
      reactions of fuel formation and water splitting. Therefore, several rounds of
      light-induced charge separation are required to accumulate enough redox
      equivalents at the catalytic sites for the target chemistry to occur, without any
      sacrificial donors or acceptors other than the catalytic substrates. Herein, we
      discuss the challenges of such accumulative electron transfer in molecular
      systems. We present a series of closely related systems base on a Ru(II)
      polypyridine photosensitizer with appended triaryl-amine or oligo-triaryl-amine
      donors, linked to nanoporous TiO2 as the acceptor. One of the systems, based on
      dye 4, shows efficient accumulative electron transfer in high overall yield
      resulting in the formation of a two-electron charge-separated state upon
      successive excitation by two photons. In contrast, the other systems do not show
      accumulative electron transfer because of different competing reactions. This
      illustrates the difficulties in designing successful systems for this still
      largely unexplored type of reaction scheme.

PMID- 22470978
TI  - Decorating polyelectrolyte wrapped SWNTs with CdTe quantum dots for solar energy
      conversion.
AB  - We report herein on the development of a synthetic route towards
      SWNT/polyelectrolyte/QD nanohybrids. On one hand, negatively charged thioglycolic
      acid capped CdTe QDs were prepared via an aqueous solution based synthesis. On
      the other hand, SWNTs were coated with a positively charged polyelectrolyte. By
      virtue of electrostatic interactions between QDs and SWNTs, SWNT/
      polyelectrolyte/QD nanohybrids were realized, whose formation was corroborated by
      thorough spectroscopic and microscopic investigations. Of particular relevance
      are changes of the QD related emission - quantum yields and lifetimes - upon
      their integration into the nanohybrids. The latter is indicative for electronic
      communication between both the photo- and redoxactive constituents, namely QDs
      and SWNTs, whose nature is electron transfer.

PMID- 22470979
TI  - Ru complexes containing pyridine dicarboxylate ligands: electronic effects on
      their catalytic activity toward water oxidation.
AB  - Two series of mononuclear ruthenium complexes [Ru(pdc)L3] (H2pdc = 2,6
      pyridinedicarboxylic acid; L = 4-methoxypyridine, 1; pyridine, 2; pyrazine, 3)
      and [Ru(pdc)L2(dmso)] (dmso = dimethyl sulfoxide; L = 4-methoxypyridine, 4;
      pyridine, 5) were synthesized and spectroscopically characterized. Their
      catalytic activity toward water oxidation has been examined using Ce(IV)
      (Ce(NH4)2(NO3)6) as the chemical oxidant under acidic conditions. Complexes 1, 2
      and 3 are capable of catalyzing Ce(IV)-driven water oxidation while 4 and 5 are
      not active. Electronic effects on their catalytic activity were illustrated:
      electron donating groups increase the catalytic activity.

PMID- 22470980
TI  - Single-molecule fluorescence dynamics of a butadiyne-linked porphyrin dimer: the
      effect of conformational flexibility in host polymers.
AB  - We have investigated the single-molecule fluorescence dynamics of a butadiyne
      linked porphyrin dimer (Z2B) depending on the density of the poly(methyl
      methacrylate) (PMMA) matrix (5, 10, 25, and 50 mg ml(-1)). By recording single
      molecule fluorescence intensity trajectories and fluorescence lifetimes, we
      observed more frequent one-step photobleaching behavior, less frequent on-off
      behavior, and narrower fluorescence lifetime distributions in lower densities of
      PMMA polymer. In contrast, more enhanced photostability was observed in higher
      densities of PMMA polymer. These results are explained by a difference in the
      molecular surroundings depending on the change in PMMA polymer density,
      suggesting that the individual photophysical properties of Z2B are strongly
      associated with their conformations and molecular surroundings in the solid
      state. Our studies will provide further information on the structure/surroundings
      relationship of single molecules in the solid state.

PMID- 22470982
TI  - Kinetics of light-driven oxygen evolution at alpha-Fe2O3 electrodes.
AB  - The kinetics of light-driven oxygen evolution at polycrystalline alpha-Fe2O3
      layers prepared by aerosol-assisted chemical vapour deposition has been studied
      using intensity modulated photocurrent spectroscopy (IMPS). Analysis of the
      frequency-dependent IMPS response gives information about the competition between
      the 4-electron oxidation of water by photogenerated holes and losses due to
      electron-hole recombination via surface states. The very slow kinetics of oxygen
      evolution indicates the presence of a kinetic bottleneck in the overall process.
      Surface treatment of the alpha-Fe2O3 with dilute cobalt nitrate solution leads to
      a remarkable improvement in the photocurrent response, but contrary to
      expectation, the results of this study show that this is not due to catalysis of
      hole transfer but is instead the consequence of almost complete suppression of
      surface recombination.

PMID- 22470981
TI  - Artificial leaf device for solar fuel production.
AB  - Solar fuels, such as hydrogen gas produced from water and methanol produced from
      carbon dioxide reduction by artificial photosynthesis, have received considerable
      attention. In natural leaves the photosynthetic proteins are well-organized in
      the thylakoid membrane. To develop an artificial leaf device for solar low-carbon
      fuel production from CO2, a chlorophyll derivative chlorin-e6 (Chl-e6;
      photosensitizer), 1-carboxylundecanoyl-1'-methyl-4,4'-bipyrizinium bromide,
      iodide (CH3V(CH2)9COOH; the electron carrier) and formate dehydrogenase (FDH)
      (the catalyst) immobilised onto a silica-gel-based thin layer chromatography
      plate (the Chl-V-FDH device) was investigated. From luminescence spectroscopy
      measurements, the photoexcited triplet state of Chl-e6 was quenched by the
      CH3V(CH2)9COOH moiety on the device, indicating the photoinduced electron
      transfer from the photoexcited triplet state of Chl-e6 to the CH3V(CH2)9COOH
      moiety. When the CO2-saturated sample solution containing NADPH (the electron
      donor) was flowed onto the Chl-V-FDH device under visible light irradiation, the
      formic acid concentration increased with increasing irradiation time.

PMID- 22470983
TI  - Photoinduced electron transfer in composites of conjugated polymers and
      dendrimers with branched colloidal nanoparticles.
AB  - Charge generation and separation dynamics in donor:acceptor systems based on
      composites of branched CdSe nanoparticles with a phenyl-cored thiophene
      containing dendrimer (4G1-3S), or a low-bandgap conjugated polymer (PCPDTBT) are
      reported upon exclusive excitation of the donor or the acceptor. Time-resolved
      microwave conductivity is used to study the dynamics of either transfer of holes
      from the nanoparticle to dendrimer, or conversely the transfer of electrons from
      the polymer to the nanoparticle. Higher photoconductance signals and longer decay
      times are correlated with device efficiencies, where composites with higher
      nanoparticle concentration exhibit higher solar photovoltaic power conversion
      efficiencies and an increase in external quantum efficiencies. This work
      evaluates the contribution of both components to device performance, but
      specifically the role of photoexcited nanoparticles.

PMID- 22470984
TI  - Excitons and charges at organic semiconductor heterojunctions.
AB  - All-organic heterojunction solar cells now provide very high quantum efficiencies
      for charge generation and rapidly-improving power conversion efficiencies. Charge
      generation and separation however, must overcome the strong Coulomb interactions
      between electrons and holes in these materials that is manifest also through the
      large exchange energies usually observed. We show for a polymer-polymer system
      with low charge generation efficiency that this arises through intersystem
      crossing from the photogenerated charge-transfer state to a lower lying triplet
      state, mediated by the proton hyperfine interaction, and that the activation
      barrier for full separation of electrons and holes is of the order of 250 meV. We
      observe, using transient optical spectroscopy, the processes of charge
      separation, recombination and sweep-out in efficient polymer-fullerene devices.
      We report also on the process of singlet exciton fission to form a pair of
      triplet excitons in pentacene that can later be dissociated against a
      heterojunction formed with C60.

PMID- 22470985
TI  - Artificial photosynthesis for solar fuels.
AB  - This contribution was presented as the closing lecture at the Faraday Discussion
      155 on artificial photosynthesis, held in Edinburgh Scotland, September 5-7 2011.
      The world needs new, environmentally friendly and renewable fuels to exchange for
      fossil fuels. The fuel must be made from cheap and "endless" resources that are
      available everywhere. The new research area of solar fuels aims to meet this
      demand. This paper discusses why we need a solar fuel and why electricity is not
      enough; it proposes solar energy as the major renewable energy source to feed
      from. The scientific field concerning artificial photosynthesis expands rapidly
      and most of the different scientific visions for solar fuels are briefly
      overviewed. Research strategies and the development of artificial photosynthesis
      research to produce solar fuels are overviewed. Some conceptual aspects of
      research for artificial photosynthesis are discussed in closer detail.

PMID- 22470986
TI  - [Diagnosis of dementia in non-western elderly migrants in memory clinics:
      obstacles and solutions].
AB  - In the next decade the number of non-western elderly immigrants will double in
      the Netherlands. Because of specific risk factors (hypertension, diabetes), the
      number of elderly immigrants with dementia will probably increase. Memory clinics
      are not well prepared for these patients, because health professionals lack
      knowledge about important obstacles in intercultural dementia diagnostics. They
      should consider language barriers, cultural differences, low level of education
      and illiteracy, as well as ignorance about dementia, shame and special care
      expectations of patients and their families. We give recommendations to improve
      communication, (neuropsychological) testing and counseling in clinical practice.

PMID- 22470987
TI  - [Evaluation of a family booklet on comfort care in dementia by professional and
      family caregivers].
AB  - Families of nursing home residents with dementia are usually involved in care and
      treatment decisions. To this end, family needs to be informed on the course of
      the dementia and possible palliative care. Based on a Canadian booklet, we
      developed an adapted version for use in the Netherlands. Elderly care physicians
      (n = 30), nurses (n = 38), and bereaved families (n = 59) evaluated the booklet
      and possible implementation strategies. All respondents confirmed that in
      general, there is a need of an information brochure on comfort care and end-of
      life issues for families. Most (93%) families believed they would have found the
      booklet useful when received earlier. Compared to the physicians, nurses more
      frequently found the booklet useful to most or all families (p = 0.04).
      Acceptance, as measured on an 8-item scale, was highest among families and lowest
      among physicians. Overall usefulness was often perceived as high (means 7.9 to
      8.3; scale range 0-10; SD 0.9 to 1.4) and did not differ across groups of
      respondents (p = 0.29). All respondents agreed that professional caregivers
      should have a role in providing the booklet. Additionally, half (53%; no
      difference across groups) favoured availability of the booklet through families'
      own initiative; some already before admission. In conclusion, there is a high
      need for written information on palliative care. The booklet is highly
      appreciated. A further improved version may support professional and family
      caregivers in practice.

PMID- 22470988
TI  - [Liver disease in the elderly].
AB  - A non-negligible percentage of the morbidity and mortality in older persons is
      due to liver disease. A discussion of the clinical presentation and proposed
      treatment of selected liver diseases in the elderly is therefore appropriate.
      Based on literature we will discuss the clinical course and treatment modalities
      of viral and autoimmune hepatitis, hepatocellular carcinoma and drug induced
      liver injury in the elderly.

PMID- 22470989
TI  - [Not Available].

PMID- 22470990
TI  - [Esophageal cancer. Introduction].

PMID- 22470991
TI  - [Recent advances in clinical approach to squamous cell cancer of the esophagus in
      Japan].

PMID- 22470992
TI  - [Anatomical features of the esophagus].

PMID- 22470993
TI  - [Epidemiology of esophageal cancer in Japan and other countries].

PMID- 22470994
TI  - [Population-based cancer registries of esophageal cancer].

PMID- 22470995
TI  - [Risk factors of esophageal squamous cell carcinoma].

PMID- 22470996
TI  - [Molecular biology for esophageal squamous cell carcinoma].

PMID- 22470997
TI  - [Subclassification of mucosal carcinoma of the esophagus].

PMID- 22470998
TI  - [Molecular mechanisms of generation and progression of esophageal cancer].

PMID- 22470999
TI  - [Pathogenesis of Barrett's adenocarcinoma].

PMID- 22471000
TI  - [Progress of pathologic research in esophageal cancer].

PMID- 22471001
TI  - [Histological classification of epithelial tumors and histological appearance of
      intraepithelial neoplasias of the esophagus].

PMID- 22471002
TI  - [Benign or malignant non-epithelial tumor].

PMID- 22471003
TI  - [Current staging systems for carcinoma of the esophagus and esophagogastric
      junction: their usage and problems].

PMID- 22471004
TI  - [Japanese classification of esophageal cancer, the 10th edition--Pathological
      part].

PMID- 22471005
TI  - ['Guidelines for diagnosis and treatment of carcinoma of the esophagus' revised
      version--the comparison to western countries].

PMID- 22471006
TI  - [Pre-treatment tumor staging of esophageal cancer: difficulty for accurate
      diagnosis].

PMID- 22471007
TI  - [General condition and performance status of esophageal cancer patients].

PMID- 22471008
TI  - [Diagnosis of superficial esophageal cancer by barium esophagography using flat
      panel x-ray detector].

PMID- 22471009
TI  - [Endoscopic evaluation of squamous cell carcinoma by conventional endoscopy].

PMID- 22471010
TI  - [Magnifying endoscopic observation of esophageal squamous cell carcinoma].

PMID- 22471011
TI  - [Endoscopic diagnosis of Barrett's esophageal adenocarcinoma].

PMID- 22471012
TI  - [Endocytoscopic observation of esophageal epithelial atypia in the esophagus].

PMID- 22471013
TI  - [Diagnosis of depth of invasion and lymph node metastasis of esophageal cancer
      using endoscopic ultrasonography].

PMID- 22471014
TI  - [Diagnosis of esophageal cancer and metastatic lymph node using CT and MRI].

PMID- 22471015
TI  - [Positron emission tomography].

PMID- 22471016
TI  - [Tumor marker, genetic diagnosis].

PMID- 22471017
TI  - [Diagnosis of superficial oro-hypopharyngeal carcinoma in Japanese high risk
      populations].

PMID- 22471018
TI  - [The outline of therapeutic strategy for esophageal cancer].

PMID- 22471019
TI  - [Treatment strategy for carcinoma of the cervical esophagus].

PMID- 22471020
TI  - [Treatment strategy for thoracic esophageal cancer].

PMID- 22471021
TI  - [Strategy for abdominal esophageal cancer treatment].

PMID- 22471022
TI  - [Indication of endoscopic treatment for superficial esophageal cancer].

PMID- 22471023
TI  - [EEMR-tube method].

PMID- 22471024
TI  - [Endoscopic mucosal resection--two channel technique].

PMID- 22471025
TI  - [EMR-C: endoscopic mucosal resection using cap-fitted endoscope].

PMID- 22471026
TI  - [Hook knife method of ESD for early esophageal cancer].

PMID- 22471027
TI  - [Endoscopic submucosal dissection (ESD) using triangle-tip knife (TT knife)].

PMID- 22471028
TI  - [Surgery for cancer of the cervical esophagus].

PMID- 22471029
TI  - [Standard procedure for cancer of the thoracic esophagus by right thoracotomy].

PMID- 22471030
TI  - [Esophageal reconstruction using the stomach].

PMID- 22471031
TI  - [Esophageal reconstruction with large or small intestine].

PMID- 22471032
TI  - [Thoracoscopic radical esophagectomy--left lateral position].

PMID- 22471033
TI  - [Thoracoscopic esophagectomy in the prone position for thoracic esophageal
      carcinoma].

PMID- 22471034
TI  - [Prone esophagectomy with ropeway technique intending complete lymph node
      dissection of the mediastinum with thoracic duct excision for esophageal squamous
      cell carcinoma].

PMID- 22471035
TI  - [Robotic esophagectomy in prone position for esophageal cancer].

PMID- 22471036
TI  - [Surgical treatment for abdominal esophageal cancer].

PMID- 22471037
TI  - [Mediastinoscope-assisted transhiatal esophagectomy for esophageal cancer].

PMID- 22471038
TI  - [Surgery for cancers at the esophagogastric junction and Barrett's esophageal
      cancers].

PMID- 22471039
TI  - [Sentinel node navigation surgery].

PMID- 22471040
TI  - [Neoadjuvant and adjuvant therapy].

PMID- 22471041
TI  - [Chemotherapy for esophageal cancer].

PMID- 22471042
TI  - [Radical radiotherapy for esophageal cancer].

PMID- 22471043
TI  - [Palliative radiation therapy for esophageal cancer].

PMID- 22471044
TI  - [Heavy ion radiotherapy for esophageal cancer].

PMID- 22471045
TI  - [Chemoradiotherapy].

PMID- 22471046
TI  - [Salvage surgery after chemoradiotherapy for esophageal cancer].

PMID- 22471047
TI  - [LASER treatment].

PMID- 22471048
TI  - [Palliation for advanced esophageal cancer (stenting and bypass operation)].

PMID- 22471049
TI  - [Recent advancement of esophageal cancer gene therapy].

PMID- 22471050
TI  - [Immunotherapy, vaccination].

PMID- 22471051
TI  - [Follow-up method after treatment for esophageal cancer].

PMID- 22471052
TI  - [Recurrence after endoscopic mucosal resection].

PMID- 22471053
TI  - [Recurrence after curative esophagectomy].

PMID- 22471054
TI  - [Recurrence after definitive chemoradiotherapy].

PMID- 22471055
TI  - [Palliative care for patients with esophageal cancer].

PMID- 22471056
TI  - [Clinical pathway for esophagectomy for esophageal cancer].

PMID- 22471057
TI  - [Nutritional management for esophageal cancer].

PMID- 22471058
TI  - [Voice restoration after laryngectomy].

PMID- 22471059
TI  - [Multi-institutional cooperative clinical trial for esophageal cancer in Japan
      (JCOG trial)].

PMID- 22471060
TI  - [Multicenter clinical trials for superficial esophageal carcinoma].

PMID- 22471061
TI  - [Multicenter clinical trial for esophageal cancer in foreign countries].

PMID- 22471062
TI  - [Informed consent for esophageal cancer].

PMID- 22471063
TI  - [Present status and problems of screening for esophageal cancers].

PMID- 22471064
TI  - [Esophageal cancer treatment in DPC system].

PMID- 22471065
TI  - [Effect of endoscopic treatment for esophageal cancer on medical economy].

PMID- 22471066
TI  - Facilities tap fresh ideas, new technology.

PMID- 22471067
TI  - New quality initiative sets high bar.

PMID- 22471068
TI  - Palazzo favors competition to help cure health care woes.

PMID- 22471069
TI  - Activities: what is appropriate?

PMID- 22471070
TI  - A new look at online staff training.

PMID- 22471071
TI  - Gene flow matters in switchgrass (Panicum virgatum L.), a potential widespread
      biofuel feedstock.
AB  - There currently exists a large push for the use, improvement, and expansion via
      landscape modification of dedicated biofuel crops (feedstocks) in the United
      States and in many parts of the world. Ecological concerns have been voiced
      because many biofuel feedstocks exhibit characteristics associated with
      invasiveness, and due to potential negative consequences of agronomic genes in
      native wild populations. Seed purity concerns for biofuel feedstock cultivars
      whose seeds would be harvested in agronomic fields also exist from the
      agribusiness sector. The common thread underlying these concerns, which have
      regulatory implications, is gene flow; thus detailed knowledge of gene flow in
      biofuel crop plants is important in the formulation of environmental risk
      management plans. Here, we synthesize the current state of knowledge of gene flow
      in an exemplary biofuel crop, switchgrass (Panicum virgatum L.), which is native
      to eastern North America and is currently experiencing conventional and
      technological advances in biomass yields and ethanol production. Surprisingly
      little is known regarding aspects of switchgrass pollen flow and seed dispersal,
      and whether native populations of conspecific or congeneric relatives will
      readily cross with current agronomic switchgrass cultivars. We pose that filling
      these important gaps will be required to confront the sustainability challenges
      of widespread planting of biofuel feedstocks.

PMID- 22471072
TI  - Midwest U.S. landscape change to 2020 driven by biofuel mandates.
AB  - Meeting future biofuel targets set by the 2007 Energy Independence and Security
      Act (EISA) will require a substantial increase in production of corn. The
      Midwest, which has the highest overall crop production capacity, is likely to
      bear the brunt of the biofuel-driven changes. In this paper, we set forth a
      method for developing a possible future landscape and evaluate changes in
      practices and production between base year (BY) 2001 and biofuel target (BT)
      2020. In our BT 2020 Midwest landscape, a total of 25 million acres (1 acre =
      0.40 ha) of farmland was converted from rotational cropping to continuous corn.
      Several states across the Midwest had watersheds where continuous corn planting
      increased by more than 50%. The output from the Center for Agriculture and Rural
      Development (CARD) econometric model predicted that corn grain production would
      double. In our study we were able to get within 2% of this expected corn
      production. The greatest increases in corn production were in the Corn Belt as a
      result of conversion to continuous corn planting. In addition to changes to
      cropping practices as a result of biofuel initiatives we also found that urban
      growth would result in a loss of over 7 million acres of productive farmland by
      2020. We demonstrate a method which successfully combines economic model output
      with gridded land cover data to create a spatially explicit detailed
      classification of the landscape across the Midwest. Understanding where changes
      are likely to take place on the landscape will enable the evaluation of trade
      offs between economic benefits and ecosystem services allowing proactive
      conservation and sustainable production for human well-being into the future.

PMID- 22471073
TI  - Variable effects of a generalist parasitoid on a biocontrol seed predator and its
      target weed.
AB  - Biological control (the importation of enemies from an invader's native range) is
      often considered our best chance of controlling the most widespread invaders.
      Ideally, the agent reduces invader abundance to some acceptably low level, and
      the two coexist at low density with the agent providing continuous control over
      the long-term. But the outcome may be complicated when the agent is attacked by
      native predators and parasites. We used a spatially explicit, discrete-time,
      individual-based, coupled plant-seed predator-parasitoid model to estimate the
      impact of the biocontrol agent Eustenopus villosus (a seed predator) on the
      invasive, annual weed Centaurea solstitialis, both with and without the
      generalist parasitoid Pyemotes tritici. We estimated the agent's ability to
      reduce plant density, spread rate, and population growth rate over 50 years. We
      used long-term demographic data from two sites in central California, USA, to
      parameterize the model and assess how populations in different climatic zones
      might respond differently to the agent and the parasitoid. We found that the
      biocontrol agent reduced plant density (relative to predictions for an
      uncontrolled invasion), but its impact on the invader's spread rate was modest
      and inconsistent. The agent had no long-term impact on population growth rate
      (lambda). Parasitism caused a trophic cascade, the strength of which varied
      between sites. At our coastal site, the parasitoid entirely eliminated the impact
      of the agent on the plant. At our Central Valley site, even when parasitized, the
      agent significantly reduced plant density and spread rate over several decades
      (although to a lesser degree than when it was not parasitized), but not invader
      lambda. Surprisingly, we also found that the length of time the invader was
      allowed to spread across the landscape prior to introducing the agent (5, 25, or
      50 years) had little influence over its ability to control the weed in the long
      term. This is encouraging news for land managers attempting to control invasive
      plants that have already established widespread, high-density populations.
      Unfortunately, our results also show that attack by the native generalist
      parasitoid had a larger influence over how effectively the agent reduced invader
      performance.

PMID- 22471074
TI  - Co-infection patterns and geographic distribution of a complex pathosystem
      targeted by pathogen-resistant plants.
AB  - Increasingly, pathogen-resistant (PR) plants are being developed to reduce the
      agricultural impacts of disease. However PR plants also have the potential to
      result in increased invasiveness of nontarget host populations and so pose a
      potential threat to nontarget ecosystems. In this paper we use a new framework to
      investigate geographical variation in the potential risk associated with
      unintended release of genetically modified alfalfa mosaic virus (AMV)-resistant
      Trifolium repens (white clover) into nontarget host populations containing AMV,
      clover yellow vein virus (ClYVV), and white clover mosaic virus (WCIMV) in
      southeastern Australia. Surveys of 213 sites in 37 habitat types over a 300 000
      km2 study region showed that T. repens is a significant weed of many high
      conservation-value habitats in southeastern Australia and that AMV, ClYVV, and
      WClMV occur in 15-97% of nontarget host populations. However, T. repens abundance
      varied with site disturbance, habitat conservation value, and proximity to
      cropping, and all viral pathogens had distinct geographic distributions and
      infection patterns. Virus species frequently co-infected host plants and
      displayed nonindependent distributions within host populations, although co
      infection patterns varied across the study region. Our results clearly illustrate
      the complexity of conducting environmental risk assessments that involve
      geographically widespread, invasive pasture species and demonstrate the general
      need for targeted, habitat- and pathosystem-specific studies prior to the process
      of tiered risk assessment.

PMID- 22471075
TI  - Effect of nitrogen deposition on China's terrestrial carbon uptake in the context
      of multifactor environmental changes.
AB  - The amount of atmospheric nitrogen (N) deposited on the land surface has
      increased globally and by nearly five times in China from 1901 to 2005. Little is
      known about how elevated reactive N input has affected the carbon (C)
      sequestration capability of China's terrestrial ecosystems, largely due to the
      lack of reliable data on N deposition. Here we have used a newly developed data
      set of historical N deposition at a spatial resolution of 10 km x 10 km in
      combination with other gridded historical information on climate, atmospheric
      composition, land use, and land management practices to drive a process-based
      ecosystem model, the dynamic land ecosystem model (DLEM) for examining how
      increasing N deposition and its interactions with other environmental changes
      have affected C fluxes and storage in China's terrestrial ecosystems during 1901
      2005. Our model simulations indicate that increased N deposition has resulted in
      a net C sink of 62 Tg C/yr (1 Tg = 1012 g) in China's terrestrial ecosystems,
      totaling up to 6.51 Pg C (1 Pg = 10(15) g) in the past 105 years. During the
      study period, the N-induced C sequestration can compensate for more than 25% of
      fossil-fuel CO2 emission from China. The largest C sink was found in southeast
      China, a region that experienced the most significant increase of N deposition in
      the period 1901-2005. However, the net primary productivity induced by per-unit N
      deposition (referred to as ecosystem N use efficiency, ENUE, in this paper) has
      leveled off or declined since the 1980s. This indicates that part of the
      deposited N may not be invested to stimulate plant growth, but instead leave the
      ecosystem by various pathways. Except shrubland and northwest/southwest China,
      signs of N saturation are apparent in the rest major biome types and regions,
      with ENUE peaking in the 1980s and leveling off or declining thereafter.
      Therefore, to minimize the excessive N pollution while keeping the N-stimulated C
      uptake in China's terrestrial ecosystems, optimized management practices should
      be taken to increase N use efficiency rather than to keep raising N input level
      in the near future.

PMID- 22471076
TI  - Soil C and N changes with afforestation of grasslands across gradients of
      precipitation and plantation age.
AB  - Afforestation, the conversion of unforested lands to forests, is a tool for
      sequestering anthropogenic carbon dioxide into plant biomass. However, in
      addition to altering biomass, afforestation can have substantial effects on soil
      organic carbon (SOC) pools, some of which have much longer turnover times than
      plant biomass. An increasing body of evidence suggests that the effect of
      afforestation on SOC may depend on mean annual precipitation (MAP). The goal of
      this study was to test how labile and bulk pools of SOC and total soil nitrogen
      (TN) change with afforestation across a rainfall gradient of 600-1500 mm in the
      Rio de la Plata grasslands of Argentina and Uruguay. The sites were all former
      grasslands planted with Eucalyptus spp. Overall, we found that afforestation
      increased (up to 1012 kg C x ha(-1) x yr(-1)) or decreased (as much as 1294 kg C
      x ha(-1) x yr(-1)) SOC pools in this region and that these changes were
      significantly related to MAP. Drier sites gained, and wetter sites lost, SOC and
      TN (r2 = 0.59, P = 0.003; and r2 = 0.57, P = 0.004, respectively). Labile C and N
      in microbial biomass and extractable soil pools followed similar patterns to bulk
      SOC and TN. Interestingly, drier sites gained more SOC and TN as plantations
      aged, while losses reversed as plantations aged in wet sites, suggesting that
      plantation age in addition to precipitation is a critical driver of changes in
      soil organic matter with afforestation. This new evidence implies that longer
      intervals between harvests for plantations could improve SOC storage,
      ameliorating the negative trends found in humid sites. Our results suggest that
      the value of afforestation as a carbon sequestration tool should be considered in
      the context of precipitation and age of the forest stand.

PMID- 22471077
TI  - Use of land facets to design linkages for climate change.
AB  - Least-cost modeling for focal species is the most widely used method for
      designing conservation corridors and linkages. However, these linkages have been
      based on current species' distributions and land cover, both of which will change
      with large-scale climate change. One method to develop corridors that facilitate
      species' shifting distributions is to incorporate climate models into their
      design. But this approach is enormously complex and prone to error propagation.
      It also produces outputs at a grain size (km2) coarser than the grain at which
      conservation decisions are made. One way to avoid these problems is to design
      linkages for the continuity and interspersion of land facets, or recurring
      landscape units of relatively uniform topography and soils. This coarse-filter
      approach aims to conserve the arenas of biological activity rather than the
      temporary occupants of those arenas. In this paper, we demonstrate how land
      facets can be defined in a rule-based and adaptable way, and how they can be used
      for linkage design in the face of climate change. We used fuzzy c-means cluster
      analysis to define land facets with respect to four topographic variables
      (elevation, slope angle, solar insolation, and topographic position), and least
      cost analysis to design linkages that include one corridor per land facet. To
      demonstrate the flexibility of our procedures, we designed linkages using land
      facets in three topographically diverse landscapes in Arizona, USA. Our
      procedures can use other variables, including soil variables, to define land
      facets. We advocate using land facets to complement, rather than replace,
      existing focal species approaches to linkage design. This approach can be used
      even in regions lacking land cover maps and is not affected by the bias and
      patchiness common in species occurrence data.

PMID- 22471078
TI  - Environmental filtering and land-use history drive patterns in biomass
      accumulation in a mediterranean-type landscape.
AB  - Aboveground biomass (AGB) reflects multiple and often undetermined ecological and
      land-use processes, yet detailed landscape-level studies of AGB are uncommon due
      to the difficulty in making consistent measurements at ecologically relevant
      scales. Working in a protected mediterranean-type landscape (Jasper Ridge
      Biological Preserve, California, USA), we combined field measurements with
      remotely sensed data from the Carnegie Airborne Observatory's light detection and
      ranging (lidar) system to create a detailed AGB map. We then developed a
      predictive model using a maximum of 56 explanatory variables derived from
      geologic and historic-ownership maps, a digital elevation model, and geographic
      coordinates to evaluate possible controls over currently observed AGB patterns.
      We tested both ordinary least-squares regression (OLS) and autoregressive
      approaches. OLS explained 44% of the variation in AGB, and simultaneous
      autoregression with a 100-m neighborhood improved the fit to an r2 = 0.72, while
      reducing the number of significant predictor variables from 27 variables in the
      OLS model to 11 variables in the autoregressive model. We also compared the
      results from these approaches to a more typical field-derived data set; we
      randomly sampled 5% of the data 1000 times and used the same OLS approach each
      time. Environmental filters including incident solar radiation, substrate type,
      and topographic position were significant predictors of AGB in all models. Past
      ownership was a minor but significant predictor, despite the long history of
      conservation at the site. The weak predictive power of these environmental
      variables, and the significant improvement when spatial autocorrelation was
      incorporated, highlight the importance of land-use history, disturbance regime,
      and population dynamics as controllers of AGB.

PMID- 22471079
TI  - North American vegetation model for land-use planning in a changing climate: a
      solution to large classification problems.
AB  - Data points intensively sampling 46 North American biomes were used to predict
      the geographic distribution of biomes from climate variables using the Random
      Forests classification tree. Techniques were incorporated to accommodate a large
      number of classes and to predict the future occurrence of climates beyond the
      contemporary climatic range of the biomes. Errors of prediction from the
      statistical model averaged 3.7%, but for individual biomes, ranged from 0% to
      21.5%. In validating the ability of the model to identify climates without
      analogs, 78% of 1528 locations outside North America and 81% of land area of the
      Caribbean Islands were predicted to have no analogs among the 46 biomes. Biome
      climates were projected into the future according to low and high greenhouse gas
      emission scenarios of three General Circulation Models for three periods, the
      decades surrounding 2030, 2060, and 2090. Prominent in the projections were (1)
      expansion of climates suitable for the tropical dry deciduous forests of Mexico,
      (2) expansion of climates typifying desertscrub biomes of western USA and
      northern Mexico, (3) stability of climates typifying the evergreen-deciduous
      forests of eastern USA, and (4) northward expansion of climates suited to
      temperate forests, Great Plains grasslands, and montane forests to the detriment
      of taiga and tundra climates. Maps indicating either poor agreement among
      projections or climates without contemporary analogs identify geographic areas
      where land management programs would be most equivocal. Concentrating efforts and
      resources where projections are more certain can assure land managers a greater
      likelihood of success.

PMID- 22471080
TI  - Whitebark pine (Pinus albicaulis) assisted migration potential: testing
      establishment north of the species range.
AB  - The translocation of species into habitable locations outside of their current
      ranges, termed assisted migration, has been proposed as a means of saving
      vulnerable species from extinction as a result of climate change. We explore the
      use of this controversial technique using a threatened keystone species in
      western North America, whitebark pine (Pinus albicaulis), as a case study.
      Species distribution models predict that whitebark pine will be extirpated from
      most of its current range as temperatures rise over the next 70 years. However,
      the same models indicate that a large area within northwestern British Columbia,
      Canada, is climatically suitable for the species under current conditions and
      will remain so throughout the 21st century. To test the capacity of whitebark
      pine to establish relative to climatic and habitat features within its predicted
      climatic range, we planted seeds from seven populations in eight locations
      spanning from 600 km southeast to 800 km northwest of the northern boundary of
      the current species range. During the first three growing seasons, germination
      occurred in all locations. Nearly three times as many treated (induced maturation
      and broken dormancy) than untreated seeds germinated, and most treated seeds
      germinated a year earlier than the untreated seeds. Germination, survival, and
      growth were primarily influenced by seed mass, site climate conditions related to
      the duration of snow cover, and provenance temperature. Our experiment provides a
      preliminary test of models predicting the existence of climatically suitable
      whitebark pine habitat north of the current species ranges. More broadly, our
      techniques and results inform the development of scientific guidelines for
      assisting the migration of other species that are highly threatened by climate
      change. Applied case studies of this kind are critical for assessing the utility
      of species distribution models as conservation planning tools.

PMID- 22471081
TI  - Height-growth response to climatic changes differs among populations of Douglas
      fir: a novel analysis of historic data.
AB  - Projected climate change will affect existing forests, as substantial changes are
      predicted to occur during their life spans. Species that have ample intraspecific
      genetic differentiation, such as Douglas-fir (Pseudotsuga menziesii (Mirb.)
      Franco), are expected to display population-specific growth responses to climate
      change. Using a mixed-effects modeling approach, we describe three-year height
      (HT) growth response to changes in climate of interior Douglas-fir populations.
      We incorporate climate information at the population level, yielding a model that
      is specific to both species and population. We use data from provenance tests
      from previous studies that comprised 236 populations from Idaho, Montana, and
      eastern Washington, USA. The most sensitive indicator of climate was the mean
      temperature of the coldest month. Population maximum HT and HT growth response to
      changes in climate were dependent on seed source climate. All populations had
      optimum HT growth when transferred to climates with warmer winters; those
      originating in sites with the warmest winters were taller across sites and had
      highest HT growth at transfer distances closest to zero; those from colder
      climates were shortest and had optimum HT growth when transferred the farthest.
      Although this differential response damped the height growth differences among
      populations, cold-climate populations still achieved their maximum growth at
      lower temperatures than warm-climate populations. The results highlight the
      relevance of understanding climate change impacts at the population level,
      particularly in a species with ample genetic variation among populations.

PMID- 22471082
TI  - Demographic projection of high-elevation white pines infected with white pine
      blister rust: a nonlinear disease model.
AB  - Matrix population models have long been used to examine and predict the fate of
      threatened populations. However, the majority of these efforts concentrate on
      long-term equilibrium dynamics of linear systems and their underlying assumptions
      and, therefore, omit the analysis of transience. Since management decisions are
      typically concerned with the short-term (< 100 years), asymptotic analyses could
      lead to inaccurate conclusions or, worse yet, critical parameters or processes of
      ecological concern may go undetected altogether. We present a stage-structured,
      deterministic, nonlinear, disease model which is parameterized for the population
      dynamics of high-elevation white pines in the face of infection with white pine
      blister rust (WPBR). We evaluate the model using newly developed software to
      calculate sensitivity and elasticity for nonlinear population models at any
      projected time step. We concentrate on two points in time, during transience and
      at equilibrium, and under two scenarios: a regenerating pine stand following
      environmental disturbance and a stand perturbed by the introduction of WPBR. The
      model includes strong density-dependent effects on population dynamics,
      particularly on seedling recruitment, and results in a structure favoring large
      trees. However, the introduction of WPBR and its associated disease-induced
      mortality alters stand structure in favor of smaller stages. Populations with
      infection probability (beta) > or = 0.1 do not reach a stable coexisting
      equilibrium and deterministically approach extinction. The model enables field
      observations of low infection prevalence among pine seedlings to be reinterpreted
      as resulting from disease-induced mortality and short residence time in the
      seedling stage. Sensitivities and elasticities, combined with model output,
      suggest that future efforts should focus on improving estimates of within-stand
      competition, infection probability, and infection cost to survivorship.
      Mitigating these effects where intervention is possible is expected to produce
      the greatest effect on population dynamics over a typical management timeframe.

PMID- 22471083
TI  - Trends and causes of severity, size, and number of fires in northwestern
      California, USA.
AB  - Research in the last several years has indicated that fire size and frequency are
      on the rise in western U.S. forests. Although fire size and frequency are
      important, they do not necessarily scale with ecosystem effects of fire, as
      different ecosystems have different ecological and evolutionary relationships
      with fire. Our study assessed trends and patterns in fire size and frequency from
      1910 to 2008 (all fires > 40 ha), and the percentage of high-severity in fires
      from 1987 to 2008 (all fires > 400 ha) on the four national forests of
      northwestern California. During 1910-2008, mean and maximum fire size and total
      annual area burned increased, but we found no temporal trend in the percentage of
      high-severity fire during 1987-2008. The time series of severity data was
      strongly influenced by four years with region-wide lightning events that burned
      huge areas at primarily low-moderate severity. Regional fire rotation reached a
      high of 974 years in 1984 and fell to 95 years by 2008. The percentage of high
      severity fire in conifer-dominated forests was generally higher in areas
      dominated by smaller-diameter trees than in areas with larger-diameter trees. For
      Douglas-fir forests, the percentage of high-severity fire did not differ
      significantly between areas that re-burned and areas that only burned once (10%
      vs. 9%) when re-burned within 30 years. Percentage of high-severity fire
      decreased to 5% when intervals between first and second fires were > 30 years. In
      contrast, in both mixed-conifer and fir/high-elevation conifer forests, the
      percentage of high-severity fire was less when re-burned within 30 years compared
      to first-time burned (12% vs. 16% for mixed conifer; 11% vs. 19% for fir/high
      elevation conifer). Additionally, the percentage of high-severity fire did not
      differ whether the re-burn interval was less than or greater than 30 years. Years
      with larger fires and greatest area burned were produced by region-wide lightning
      events, and characterized by less winter and spring precipitation than years
      dominated by smaller human-ignited fires. Overall percentage of high-severity
      fire was generally less in years characterized by these region-wide lightning
      events. Our results suggest that, under certain conditions, wildfires could be
      more extensively used to achieve ecological and management objectives in
      northwestern California.

PMID- 22471084
TI  - Community occupancy responses of small mammals to restoration treatments in
      ponderosa pine forests, northern Arizona, USA.
AB  - In western North American conifer forests, wildfires are increasing in frequency
      and severity due to heavy fuel loads that have accumulated after a century of
      fire suppression. Forest restoration treatments (e.g., thinning and/or burning)
      are being designed and implemented at large spatial and temporal scales in an
      effort to reduce fire risk and restore forest structure and function. In
      ponderosa pine (Pinus ponderosa) forests, predominantly open forest structure and
      a frequent, low-severity fire regime constituted the evolutionary environment for
      wildlife that persisted for thousands of years. Small mammals are important in
      forest ecosystems as prey and in affecting primary production and decomposition.
      During 2006-2009, we trapped eight species of small mammals at 294 sites in
      northern Arizona and used occupancy modeling to determine community responses to
      thinning and habitat features. The most important covariates in predicting small
      mammal occupancy were understory vegetation cover, large snags, and treatment.
      Our analysis identified two generalist species found at relatively high occupancy
      rates across all sites, four open-forest species that responded positively to
      treatment, and two dense-forest species that responded negatively to treatment
      unless specific habitat features were retained. Our results indicate that all
      eight small mammal species can benefit from restoration treatments, particularly
      if aspects of their evolutionary environment (e.g., large trees, snags, woody
      debris) are restored. The occupancy modeling approach we used resulted in precise
      species-level estimates of occupancy in response to habitat attributes for a
      greater number of small mammal species than in other comparable studies. We
      recommend our approach for other studies faced with high variability and broad
      spatial and temporal scales in assessing impacts of treatments or habitat
      alteration on wildlife species. Moreover, since forest planning efforts are
      increasingly focusing on progressively larger treatment implementation, better
      and more efficiently obtained ecological information is needed to inform these
      efforts.

PMID- 22471085
TI  - Traits, not origin, explain impacts of plants on larval amphibians.
AB  - Managing habitats for the benefit of native fauna is a priority for many
      government and private agencies. Often, these agencies view nonnative plants as a
      threat to wildlife habitat, and they seek to control or eradicate nonnative plant
      populations. However, little is known about how nonnative plant invasions impact
      native fauna, and it is unclear whether managing these plants actually improves
      habitat quality for resident animals. Here, we compared the impacts of native and
      nonnative wetland plants on three species of native larval amphibians; we also
      examined whether plant traits explain the observed impacts. Specifically, we
      measured plant litter quality (carbon : nitrogen : phosphorus ratios, and
      percentages of lignin and soluble phenolics) and biomass, along with a suite of
      environmental conditions known to affect larval amphibians (hydroperiod,
      temperature, dissolved oxygen, and pH). Hydroperiod and plant traits, notably
      soluble phenolics, litter C:N ratio, and litter N:P ratio, impacted the
      likelihood that animals metamorphosed, the number of animals that metamorphosed,
      and the length of larval period. As hydroperiod decreased, the likelihood that
      amphibians achieved metamorphosis and the percentage of tadpoles that
      successfully metamorphosed also decreased. Increases in soluble phenolics, litter
      N:P ratio, and litter C:N ratio decreased the likelihood that tadpoles achieved
      metamorphosis, decreased the percentage of tadpoles metamorphosing, decreased
      metamorph production (total metamorph biomass), and increased the length of
      larval period. Interestingly, we found no difference in metamorphosis rates and
      length of larval period between habitats dominated by native and nonnative
      plants. Our findings have important implications for habitat management. We
      suggest that to improve habitats for native fauna, managers should focus on
      assembling a plant community with desirable traits rather than focusing only on
      plant origin.

PMID- 22471086
TI  - Collapse and reorganization of a food web of Mwanza Gulf, Lake Victoria.
AB  - Lake Victoria in East Africa is the world's second largest freshwater system.
      Over the past century the ecosystem has undergone drastic changes. Some 30 years
      after the introduction of Nile perch (Lates niloticus) and Nile tilapia
      (Oreochromis niloticus) in the 1950s, the highly diverse community of native
      haplochromines collapsed, leaving a system dominated by only four species: the
      native cyprinid dagaa (Rastrineobola argentea) and shrimp (Caridina nilotica), as
      well as the introduced Nile perch and Nile tilapia. More recently, an unexpected
      resurgence of haplochromines has been reported. To understand these changes in
      terms of ecosystem functioning and of changes in growth of trophic groups, we
      created mass balances of the food web near Mwanza, Tanzania, before, during, and
      after the Nile perch boom (1977, 1987, and 2005), using the application ECOPATH.
      We connected these mass balances with a dynamic model assuming linear trends in
      net growth rates of the trophic groups. Our analysis suggests that the Nile perch
      boom initially altered the biomass distribution over trophic levels. Also,
      results indicate that not only fishing but also changes at the detritivores'
      trophic level might have played an important role in driving changes in the
      system. Both the mass balances and the dynamic model connecting them reveal that,
      after a major distortion during the Nile perch boom, the biomass distribution
      over the main trophic levels had largely recovered its original (1977) state by
      2005. However, no such return appeared in terms of community structure.
      Biodiversity in the new state is dramatically lower, consisting of introduced
      species and a few native surviving species. We conclude that at an aggregate
      level Lake Victoria's ecosystem has proved to be resilient in the sense that its
      overall trophic structure has apparently recovered after a major perturbation. By
      contrast, its intricate functional structure and associated biodiversity have
      proved to be fragile and seem unlikely to recover.

PMID- 22471087
TI  - Managing floodplain-forest restoration in European river landscapes combining
      ecological and flood-protection issues.
AB  - Throughout Europe the demands for improved flood protection on the one hand and
      the requirements to maintain and enhance floodplain forests on the other are
      perceived as conflicting goals in river-basin management, revealing the urgent
      need for strategies to combine both issues. We developed an interdisciplinary
      approach for floodplain-forest restoration identifying sites suitable for
      reforestations from both an ecological and hydraulic point of view. In the
      ecological module, habitat-distribution models are developed providing
      information on ecologically suitable sites. In the hydraulic module, a two
      dimensional hydrodynamic-numerical model (2D-HN model) delivers the requested
      hydraulic information. The output of the two models is intersected. Subsequently,
      in an iterative procedure, the potential of plantings without exceeding critical
      water levels can be identified by hydraulic evaluation using the 2D-HN-model. The
      approach is exemplified using two reforestation scenarios at the Elbe River,
      Germany, showing considerable potential for softwood forest establishment without
      negative hydraulic effects. The approach reported here provides a solution for a
      severe conflict in river-basin management that hampers the reestablishment of the
      strongly threatened floodplain forests in Europe. Alternative measures to enhance
      floodplain-forest regeneration feasible under certain preconditions are discussed
      in the context of the current state of European large rivers.

PMID- 22471088
TI  - Understanding multiple ecological responses to anthropogenic disturbance: rivers
      and potential flow regime change.
AB  - Human-induced alteration of the natural flow regime is a major threat to
      freshwater ecosystems and biodiversity. The effects of hydrological alteration on
      the structural and functional attributes of riverine communities are expected to
      be multiple and complex, and they may not be described easily by a single model.
      Based on existing knowledge of key hydrological and ecological attributes, we
      explored potential effects of a flow-regulation scenario on macroinvertebrate
      assemblage composition and diversity in two river systems in Australia's
      relatively undeveloped wet-dry tropics. We used a single Bayesian belief network
      (BBN) to model potential changes in multiple assemblage attributes within each
      river type during dry and wet seasons given two flow scenarios: the current, near
      natural flow condition, and flow regulation. We then used multidimensional
      scaling (MDS) ordination to visually summarize and compare the most probable
      attributes of assemblages and their environment under the different scenarios.
      The flow-regulation scenario provided less certainty in the ecological responses
      of one river type during the dry season, which reduced the ability to make
      predictions from the BBN outputs directly. However, visualizing the BBN results
      in an ordination highlighted similarities and differences between the scenarios
      that may have been otherwise difficult to ascertain. In particular, the MDS
      showed that flow regulation would reduce the seasonal differentiation in
      hydrology and assemblage characteristics that is expected under the current low
      level of development. Our approach may have wider application in understanding
      ecosystem responses to different river management practices and should be
      transferred easily to other ecosystems or biotic assemblages to provide
      researchers, managers, and decision makers an enhanced understanding of
      ecological responses to potential anthropogenic disturbance.

PMID- 22471089
TI  - Greenhouse gas fluxes in southeastern U.S. coastal plain wetlands under
      contrasting land uses.
AB  - Whether through sea level rise or wetland restoration, agricultural soils in
      coastal areas will be inundated at increasing rates, renewing connections to
      sensitive surface waters and raising critical questions about environmental trade
      offs. Wetland restoration is often implemented in agricultural catchments to
      improve water quality through nutrient removal. Yet flooding of soils can also
      increase production of the greenhouse gases nitrous oxide and methane,
      representing a potential environmental trade-off. Our study aimed to quantify and
      compare greenhouse gas emissions from unmanaged and restored forested wetlands,
      as well as actively managed agricultural fields within the North Carolina coastal
      plain, USA. In sampling conducted once every two months over a two-year
      comparative study, we found that soil carbon dioxide flux (range: 8000-64 800 kg
      CO2 x ha(-1) x yr(-1)) comprised 66-100% of total greenhouse gas emissions from
      all sites and that methane emissions (range: -6.87 to 197 kg CH4 x ha(-1) x yr(
      1)) were highest from permanently inundated sites, while nitrous oxide fluxes
      (range: -1.07 to 139 kg N2O x ha(-1) x yr(-1)) were highest in sites with lower
      water tables. Contrary to predictions, greenhouse gas fluxes (as CO2 equivalents)
      from the restored wetland were lower than from either agricultural fields or
      unmanaged forested wetlands. In these acidic coastal freshwater ecosystems, the
      conversion of agricultural fields to flooded young forested wetlands did not
      result in increases in greenhouse gas emissions.

PMID- 22471090
TI  - Floodplain restoration enhances denitrification and reach-scale nitrogen removal
      in an agricultural stream.
AB  - Streams of the agricultural Midwest, USA, export large quantities of nitrogen,
      which impairs downstream water quality, most notably in the Gulf of Mexico. The
      two-stage ditch is a novel restoration practice, in which floodplains are
      constructed alongside channelized ditches. During high flows, water flows across
      the floodplains, increasing benthic surface area and stream water residence time,
      as well as the potential for nitrogen removal via denitrification. To determine
      two-stage ditch nitrogen removal efficacy, we measured denitrification rates in
      the channel and on the floodplains of a two-stage ditch in north-central Indiana
      for one year before and two years after restoration. We found that instream rates
      were similar before and after the restoration, and they were influenced by
      surface water NO3- concentration and sediment organic matter content.
      Denitrification rates were lower on the constructed floodplains and were
      predicted by soil exchangeable NO3- concentration. Using storm flow simulations,
      we found that two-stage ditch restoration contributed significantly to NO3-
      removal during storm events, but because of the high NO3- loads at our study
      site, < 10% of the NO3- load was removed under all storm flow scenarios. The
      highest percentage of NO3- removal occurred at the lowest loads; therefore, the
      two-stage ditch's effectiveness at reducing downstream N loading will be
      maximized when the practice is coupled with efforts to reduce N inputs from
      adjacent fields.

PMID- 22471091
TI  - How long can fisheries management delay action in response to ecosystem and
      climate change?
AB  - Sustainable management of fisheries is often compromised by management delaying
      implementation of regulations that reduce harvest, in order to maintain higher
      catches in the short-term. Decreases or increases in fish population growth rate
      driven by environmental change, including ecosystem and climate change, affect
      the harvest that can be taken sustainably. If not acted on rapidly, environmental
      change could result in unsustainable fishing or missed opportunity for higher
      catches. Using simulation models of harvested fish populations influenced by
      environmental change, we explore how long fisheries managers can afford to wait
      before changing harvest regulations in response to changes in population growth.
      If environmental change causes population declines, delays greater than five
      years increase the probability of population collapse. Species with fast and
      highly variable population growth rates are more susceptible to collapse under
      delays and should be a priority for revised management where delays occur.
      Generally, the long-term cost of delay, in terms of lost fishing opportunity,
      exceeds the short-term benefits of overfishing. Lowering harvest limits and
      monitoring for environmental change can alleviate the impact of delays; however,
      these measures may be more costly than reducing delays. We recommend that
      management systems that allow rapid responses to population growth changes be
      enacted for fisheries management to adapt to ecosystem and climate change.

PMID- 22471092
TI  - Risk spreading, connectivity, and optimal reserve spacing.
AB  - Two important processes determining the dynamics of spatially structured
      populations are dispersal and the spatial covariance of demographic fluctuations.
      Spatially explicit approaches to conservation, such as reserve networks, must
      consider the tension between these two processes and reach a balance between
      distances near enough to maintain connectivity, but far enough to benefit from
      risk spreading. Here, we model this trade-off. We show how two measures of
      metapopulation persistence depend on the shape of the dispersal kernel and the
      shape of the distance decay in demographic covariance, and we consider the
      implications of this trade-off for reserve spacing. The relative rates of
      distance decay in dispersal and demographic covariance determine whether the long
      run metapopulation growth rate, and quasi-extinction risk, peak for adjacent
      patches or intermediately spaced patches; two local maxima in metapopulation
      persistence are also possible. When dispersal itself fluctuates over time, the
      trade-off changes. Temporal variation in mean distance that propagules are
      dispersed (i.e., propagule advection) decreases metapopulation persistence and
      decreases the likelihood that persistence will peak for adjacent patches.
      Conversely, variation in diffusion (the extent of random spread around mean
      dispersal) increases metapopulation persistence overall and causes it to peak at
      shorter inter-patch distances. Thus, failure to consider temporal variation in
      dispersal processes increases the risk that reserve spacings will fail to meet
      the objective of ensuring metapopulation persistence. This study identifies two
      phenomena that receive relatively little attention in empirical work on reserve
      spacing, but that can qualitatively change the effectiveness of reserve spacing
      strategies: (1) the functional form of the distance decay in covariance among
      patch-specific demographic rates and (2) temporal variation in the shape of the
      dispersal kernel. The sensitivity of metapopulation recovery and persistence to
      how covariance of vital rates decreases with distance suggests that estimating
      the shape of this function is likely to be as important for effective reserve
      design as estimating connectivity. Similarly, because temporal variation in
      dispersal dynamics influences the effect of reserve spacing, approaches to
      reserve design that ignore such variation, and rely instead on long-term average
      dispersal patterns, are likely to lead to lower metapopulation viability than is
      actually achievable.

PMID- 22471093
TI  - Collaborative assessment of California spiny lobster population and fishery
      responses to a marine reserve network.
AB  - Assessments of the conservation and fisheries effects of marine reserves
      typically focus on single reserves where sampling occurs over narrow
      spatiotemporal scales. A strategy for broadening the collection and
      interpretation of data is collaborative fisheries research (CFR). Here we report
      results of a CFR program formed in part to test whether reserves at the Santa
      Barbara Channel Islands, USA, influenced lobster size and trap yield, and whether
      abundance changes in reserves led to spillover that influenced trap yield and
      effort distribution near reserve borders. Industry training of scientists allowed
      us to sample reserves with fishery relevant metrics that we compared with pre
      reserve fishing records, a concurrent port sampling program, fishery effort
      patterns, the local ecological knowledge (LEK) of fishermen, and fishery
      independent visual surveys of lobster abundance. After six years of reserve
      protection, there was a four- to eightfold increase in trap yield, a 5-10%
      increase in the mean size (carapace length) of legal sized lobsters, and larger
      size structure of lobsters trapped inside vs. outside of three replicate
      reserves. Patterns in trap data were corroborated by visual scuba surveys that
      indicated a four- to sixfold increase in lobster density inside reserves.
      Population increases within reserves did not lead to increased trap yields or
      effort concentrations (fishing the line) immediately outside reserve borders. The
      absence of these catch and effort trends, which are indicative of spillover, may
      be due to moderate total mortality (Z = 0.59 for legal sized lobsters outside
      reserves), which was estimated from analysis of growth and length frequency data
      collected as part of our CFR program. Spillover at the Channel Islands reserves
      may be occurring but at levels that are insufficient to influence the fishery
      dynamics that we measured. Future increases in fishing effort (outside reserves)
      and lobster biomass (inside reserves) are likely and may lead to increased
      spillover, and CFR provides an ideal platform for continued assessment of fishery
      reserve interactions.

PMID- 22471094
TI  - Spatial scale of similarity as an indicator of metacommunity stability in
      exploited marine systems.
AB  - The spatial scale of similarity among fish communities is characteristically
      large in temperate marine systems: connectivity is enhanced by high rates of
      dispersal during the larval/juvenile stages and the increased mobility of large
      bodied fish. A larger spatial scale of similarity (low beta diversity) is
      advantageous in heavily exploited systems because locally depleted populations
      are more likely to be "rescued" by neighboring areas. We explored whether the
      spatial scale of similarity changed from 1970 to 2006 due to overfishing of
      dominant, large-bodied groundfish across a 300 000-km2 region of the Northwest
      Atlantic. Annually, similarities among communities decayed slowly with increasing
      geographic distance in this open system, but through time the decorrelation
      distance declined by 33%, concomitant with widespread reductions in biomass, body
      size, and community evenness. The decline in connectivity stemmed from an erosion
      of community similarity among local subregions separated by distances as small as
      100 km. Larger fish, of the same species, contribute proportionally more viable
      offspring, so observed body size reductions will have affected maternal output.
      The cumulative effect of nonlinear maternal influences on egg/larval quality may
      have compromised the spatial scale of effective larval dispersal, which may
      account for the delayed recovery of certain member species. Our study adds strong
      support for using the spatial scale of similarity as an indicator of
      metacommunity stability both to understand the spatial impacts of exploitation
      and to refine how spatial structure is used in management plans.

PMID- 22471095
TI  - Urban ecosystem services: tree diversity and stability of tropospheric ozone
      removal.
AB  - Urban forests provide important ecosystem services, such as urban air quality
      improvement by removing pollutants. While robust evidence exists that plant
      physiology, abundance, and distribution within cities are basic parameters
      affecting the magnitude and efficiency of air pollution removal, little is known
      about effects of plant diversity on the stability of this ecosystem service.
      Here, by means of a spatial analysis integrating system dynamic modeling and
      geostatistics, we assessed the effects of tree diversity on the removal of
      tropospheric ozone (O3) in Rome, Italy, in two years (2003 and 2004) that were
      very different for climatic conditions and ozone levels. Different tree
      functional groups showed complementary uptake patterns, related to tree
      physiology and phenology, maintaining a stable community function across
      different climatic conditions. Our results, although depending on the city
      specific conditions of the studied area, suggest a higher function stability at
      increasing diversity levels in urban ecosystems. In Rome, such ecosystem
      services, based on published unitary costs of externalities and of mortality
      associated with O3, can be prudently valued to roughly US$2 and $3 million/year,
      respectively.

PMID- 22471096
TI  - Linking noninvasive genetic sampling and traditional monitoring to aid management
      of a trans-border carnivore population.
AB  - Noninvasive genetic sampling has been embraced by wildlife managers and
      ecologists, especially those charged with monitoring rare and elusive species
      over large areas. Challenges arise when desired population measures are not
      directly attainable from genetic data and when monitoring targets trans-border
      populations. Norwegian management authorities count individual brown bears (Ursus
      arctos) using noninvasive genetic sampling but express management goals in the
      annual number of bear reproductions (females that produce cubs), a measure that
      is not directly available from genetic data. We combine noninvasive genetic
      sampling data with information obtained from a long-term intensive monitoring
      study in neighboring Sweden to estimate the number of annual reproductions by
      females detected within Norway. Most female brown bears in Norway occur near the
      border with neighboring countries (Sweden, Finland, and Russia) and their
      potential reproduction can therefore only partially be credited to Norway. Our
      model includes a simulation-based method that corrects census data to account for
      this. We estimated that 4.3 and 5.7 reproductions can be credited to females
      detected with noninvasive genetic sampling in Norway in 2008 and 2009,
      respectively. These numbers fall substantially short of the national target (15
      annual reproductions). Ignoring the potential for home ranges to extend beyond
      Norway's borders leads to an increase in the estimate of the number of
      reproductions by -30%. Our study shows that combining noninvasive genetic
      sampling with information obtained from traditional intensive/invasive monitoring
      can help answer contemporary management questions in the currency desired by
      managers and policy makers. Furthermore, combining methodologies and thereby
      accounting for space use increases the accuracy of the information on which
      decisions are based. It is important that the information derived from multiple
      approaches is applicable to the same focal population and that predictions are
      cross-validated. When monitoring and management are constrained to administrative
      units, census data should be adjusted by discounting portions of individual space
      utilization that extend beyond the focal jurisdiction. Our simulation-based
      approach for making such an adjustment may be useful in other situations where
      management authorities target portions of trans-border populations.

PMID- 22471097
TI  - Assessment of monitoring power for highly mobile vertebrates.
AB  - Monitoring of population trends is a critical component of conservation
      management, and development of practical methods remains a priority, particularly
      for species that challenge more standard approaches. We used field-parameterized
      simulation models to examine the effects of different errors on monitoring power
      and compared alternative methods used with two species of threatened pteropodids
      (flying-foxes), Pteropus conspicillatus and P. poliocephalus, whose mobility
      violates assumptions of closure on short and long timescales. The influence of
      three errors on time to 80% statistical power was assessed using a Monte Carlo
      approach. The errors were: (1) failure to count all animals at a roost, (2)
      errors associated with enumeration, and (3) variability in the proportion of the
      population counted due to the movement of individuals between roosts. Even with
      perfect accuracy and precision for these errors only marginal improvements in
      power accrued (-1%), with one exception. Improving certainty in the proportion of
      the population being counted reduced time to detection of a decline by over 6 yr
      (43%) for fly-out counts and almost 10 yr (71%) for walk-through counts. This
      error derives from the movement of animals between known and unknown roost sites,
      violating assumptions of population closure, and because it applies to the entire
      population, it dominates all other sources of error. Similar errors will accrue
      in monitoring of a wide variety of highly mobile species and will also result
      from population redistribution under climate change. The greatest improvements in
      monitoring performance of highly mobile species accrue through an improved
      understanding of the proportion of the population being counted, and consequently
      monitoring of such species must be done at the scale of the species or population
      range, not at the local level.

PMID- 22471098
TI  - Diabetic nephropathy and multiorgan protection. Part I.
AB  - Diabetic nephropathy, one of the most important complications of diabetes
      mellitus, requires during its evolution protective measures defined as
      renoprotective. Since the complications of diabetes mellitus are not limited to
      diabetic nephropathy and as this is frequently associated with heart
      complications that require protective measures defined as cardioprotective,
      neurologic measures that require neuroprotection of the retina, of the large
      vessels etc., much more complex protective measures are necessary. The metabolic
      complications that are usually at the basis of the other complications at the
      level of the cell also impose measures of protection. Such an approach can have
      important practical consequences. It is a well-known fact that most patients with
      chronic kidney disease--CKD--do not reach final stages as in the meantime they
      decease because of cardiovascular diseases. Consequently, cardioprotective
      measures have to be associated with renoprotective ones, as well as protective
      measures that address other organs, in close connection with protective measures
      at metabolic level. The protective measures must also address to
      microcirculation, diabetic nephropathy being a disease that primarily affects
      microcirculation. Diabetes mellitus also frequently affects the large vessels,
      the circulatory system being usually affected in its complexity. The paper
      represents a synthesis of multiorganprotective measures in diabetic nephropathy,
      in diabetes mellitus, respectively, the concept of multiorgan protection finding
      in this disease an ideal domain of expression. The first part gives the main
      multiorgan measures: monitoring of blood pressure and, mainly, protection by
      means of the renine aldosterone (RAAS) system, multiorgan by intensive monitoring
      of glycaemia and by treatment of proteinuria. The second part presents the other
      protective measures used in diabetic nephropathy.

PMID- 22471099
TI  - The influence of left bundle branch-block and cardiac dyssynchrony on 2D-strain
      parameters in patients with heart failure complicating ischemic cardiomyopathy.
AB  - Coronary artery disease is the underlying cause in approximately two-thirds of
      patients with heart failure. Torsional and longitudinal deformations are
      essential components of left ventricular (LV) performance. Electric conduction
      defects can reduce LV ejection fraction (LVEF) and decrease cardiac output. AIM:
      To investigate the influence of left bundle branch-block (LBBB) and cardiac
      dyssynchrony on 2D-strain parameters in patients with HF complicating ischemic
      cardiomyopathy. METHODS: We analyzed 106 consecutive patients with HF
      complicating ischemic cardiomyopathy, in sinusal rhythm. LV strain, LV twist and
      LV torsion were measured by echocardiographic 2D-strain imaging. LV dyssynchrony
      was assessed using validated tissue Doppler parameters. Patients were divided
      into three groups: HF with normal LVEF (group 1), HF with reduced LVEF without
      LBBB (group 2) and with LBBB (group 3). RESULTS: LVEF, LV strain, LV torsion and
      LV twist were significantly better in group 1 (each p < 0.01). In group 3, LV
      torsion and LV twist were significantly lower compared to group 2 (0.80 +/- 0.4
      vs. 1.21 +/- 0.23 degrees/cm, p = 0.007, and 5.18 +/- 2.4 vs. 8.31 +/- 1.5
      degrees, p = 0.004, respectively), but LV strain and LVEF were not different
      between group 3 and 2 (-4.91 +/- 2.3 vs. -6.28 +/- 1.8%, p = 0.056, and 30.6 +/-
      8.8 vs. 34.4 = 8.3%, p = 0.11, respectively). Cardiac dyssynchrony induces a
      reduction of all 2D-strain analyzed parameters (each p < 0.05). CONCLUSION: In HF
      complicating ischemic cardiomyopathy, LBBB and cardiac dyssynchrony induce a
      reduction of LV strain, torsion and twist. In patients with reduced LVEF, LBBB
      induces predominantly a significant reduction ofLV torsion and LV twist, while LV
      strain was apparently not influenced.

PMID- 22471100
TI  - Stem-like cells in colorectal oncology.
AB  - Although the treatment for colorectal cancer has seen considerable progress
      during the past few years, the mortality associated with this type of tumor
      remains high. This article presents the existing methods of treatment, focusing
      on the new treatments made possible by the advances in the field of normal and
      tumor stem cells. Starting from the normal architecture of the colon and the
      properties of the cells identified in it, we sought to present a few notions
      concerning these cells which have a direct relevance for both pathology and
      treatment. The manner in which they divide (symmetrically or asymmetrically) as
      well as the molecules which control their circulation through the body are just a
      few examples which are likely to influence the treatment of colorectal cancer in
      the future.

PMID- 22471101
TI  - Glutathione reductase levels in patients with unstable angina.
AB  - Experimental evidence suggests that free-radical damage and antioxidant defense
      may play an important role in the pathogenesis of coronary heart disease. We have
      examined the association between plasmatic glutathione reductase (GR) levels and
      the prognosis of patients with unstable angina. We have evaluated 37 patients,
      under the age of 75, diagnosed with unstable angina and 19 healthy volunteers.
      The patients were divided into two groups: the first group--10 patients with
      unstable angina with readmission in the following 6 months--and the second group-
      27 patients with unstable angina and favourable evolution. GR was measured in
      dynamics during hospitalization period. After discharge, the patients were
      monitored and the following data were recorded: months of follow-up, death due to
      cardiovascular cause and onset of major cardiovascular events. In patients with
      unstable angina there was a statistically significant higher increase of GR on
      admission to the values of the control group (p < 0.0001). Subsequently,
      plasmatic levels begin to decline, so that at discharge, the GR is similar to the
      control group. Plasmatic levels of GR were statistically significantly lower in
      patients with unstable angina without cardiovascular event than in patients with
      readmission in the following months (p < 0.05). In conclusion, patients who
      experienced unstable angina and without cardiovascular events during follow-up
      had lower GR plasmatic levels and that GR activity was an independent predictor
      of cardiovascular events during follow-up.

PMID- 22471102
TI  - Elements of renal injury in patients with varicose ulcer. Preliminary study.
AB  - The kidney may be affected in the processes of microbial, viral, parasitic
      infections. Knowledge of renal disease during chronic infection, with a different
      location than the throat, is of particular importance for the practicing
      physician for the detection and prevention of impaired renal function. Chronic
      kidney disease recovered in the early stages can prevent the progression of renal
      function decline. We studied a total of 85 patients with varicose ulcers with a
      mean age of 66.78 +/- 12.09 years, hospitalized in the Clinic of Dermatology and
      a control group consisting of 110 apparently healthy individuals. Urinary
      abnormalities have been detected in 26 (30%) of patients studied. GFR < 60 ml/min
      have been detected in 14 (17%) of patients studied. CRF stage II have been
      detected in 36 (42%) of patients studied. We detected recurrent varicose ulcer in
      2 (2%) of patients studied. In two (2%) of patients during hospitalization we
      found a decrease in GFR by 15 and 12 ml/min, accompanied by an increase in serum
      creatinine from 0.7 mg % to 1 mg % in one patient and in another patient from 1.5
      mg % to 2 mg %. Urinary abnormalities detected in patients with both acute and
      recurrent erysipelas warn about renal impairment and the need for monitoring of
      the renal patients with varicose ulcers.

PMID- 22471103
TI  - Investigating the use of specific cognitive emotion regulation strategies in
      response to the experience of gingival bleeding.
AB  - The present study focuses on the extent to which undergraduates use specific
      cognitive emotion regulation strategies in response to the experience of the
      gingival bleeding. MATERIAL AND METHODS: The present study sample consisted of
      190 first year dental students. The questionnaire included information about
      socio-demographic factors, behavioral variables and self-reported oral health
      status. To measure the specific emotional cognitive strategies, the Cognitive
      Emotion Regulation Questionnaire (CERQ) was used. RESULTS: Self-reported gingival
      bleeding was associated with statistical significant higher values of self-blame
      and rumination. Participants who evaluated their self-reported gingival condition
      as poor/very poor scored higher values on rumination, catastrophising and lower
      on positive reappraisal, when compared with students with excellent gingival
      condition. Multiple linear regression analyses revealed that presence of gingival
      bleeding was an independent determinant of self-blame, rumination and putting
      into perspective. Among participants with positive self-reported gingival
      bleeding, reason for dental visits was significantly correlated with positive
      refocusing, planning, positive reappraisal, putting into perspective and
      catrastrophizing. Positive reappraisal was found to be a mediating variable in
      the relationship between gingival status and reason for dental visits. Thus,
      positive reappraisal helps to explain the association between gingival status and
      reason for dental visits. CONCLUSIONS: Helping patients to challenge these
      maladaptive cognitive emotion regulation strategies may therefore play an
      important role on the focus and content of (preventive) oral health behaviour
      interventions to be developed for patients with gingival and periodontal disease.

PMID- 22471104
TI  - Dermatomyositis and polyradiculoneuritis, a rare association.
AB  - The association between dermatomyositis and polyradiculoneuritis is rarely
      citated in the speciality literature. Our patient had at first a disorder that
      looked like dermatomyositis, then she associated polyradiculoneuritis. At the
      presentation to our hospital the two diseases were combined, being very difficult
      to differentiate. The discrimination between these two had been made by
      performing a muscular biopsy and EMG studies. This emphasizes once again their
      importance in defining the muscular impairment from the neurogenic one.

PMID- 22471105
TI  - EDs struggle with increased demand from patients with behavioral health concerns.
AB  - Busy EDs across the country are being challenged by spikes in patients presenting
      for care with behavioral health problems. Some hospitals have dealt with this
      issue by building separate units or areas within the ED designed to meet the
      needs of this patient population; however, experts suggest there is ample room
      for improvement in the way most EDs care for patients with behavioral health
      needs. Clinicians and staff need to accept responsibility for caring for patients
      with behavioral health issues, and they need to be appropriately educated and
      prepared for this task. Noting that one in every 10 suicides involves someone who
      has been seen in the ED within two months of dying, experts stress that suicide
      prevention training should be a top priority for EDs. Create a room or area
      within the ED that is away from the noise and lights so that it will have a
      soothing impact on patients who are highly distressed or agitated. Also, consider
      getting feedback from patients on steps that would make the ED more welcoming to
      clients with behavioral health issues. Look for model programs to learn from and
      consult with regarding strategies for improving behavioral health care in the ED.

PMID- 22471106
TI  - Create a welcoming, soothing environment for patients with behavioral health
      needs.

PMID- 22471107
TI  - Use routine chart reviews, training, and careful staffing decisions to root out
      under-triage in the ED.
AB  - Experts say under-triage is a serious problem in EDs across the country, and the
      issue has serious implications for patient outcomes. For example, patients who
      are deemed urgent but stable can deteriorate quickly if they are more ill than
      the triage nurse initially determined.This can lead to delays in needed care and
      worse outcomes or even death. One small study found that patients who were
      designated as Emergency Severity Index (ESI) level 3 were often under-triaged.
      Routine chart reviews can help ED nursing leaders determine whether under-triage
      is a problem, and which nurses may need added training in triage to improve their
      skills. Rather than rotating all emergency nurses through the triage role, ED
      leaders should carefully evaluate which nurses have the high-level skills needed
      to make accurate triage decisions.

PMID- 22471108
TI  - Study: reconsider the use of CT scans for patients who present with dizziness.
AB  - Researchers at Henry Ford Hospital in Detroit have found that CT scans rarely
      show evidence of serious underlying conditions in patients who present with
      dizziness, yet they are frequently ordered by ED providers. In a study conducted
      over three years, researchers found that less than 1% of CT scans performed in
      patients with dizziness yielded significant results. Instead, in most cases,
      experts say a thorough history and evaluation can help providers narrow in on a
      differential diagnosis without the expense or radiation exposure associated with
      CT. The cost of the CTs over the three-year study period was $988,200. In the
      study, the patients who had some abnormal findings on CT scans had severe
      headaches or some neurological deficits along with the dizziness. For patients
      presenting with isolated dizziness, lightheadedness or positional vertigo without
      any other symptoms, the likelihood of finding an acute, life-threatening
      abnormality on a CT scan is quite low

PMID- 22471109
TI  - [Let's not allow general internal medicine to disappear].

PMID- 22471110
TI  - [How to deal with familial dyslipidemia in clinical practice?].
AB  - Familial dyslipidemias are common in the population and correlated with increased
      risk of cardiovascular disease at young age. The early detection of individuals
      at high-risk may delay the vascular events and offer an increased quality of life
      and life expectancy. Screening is recommended in infancy in case of positive
      family history of premature cardiovascular disease. Lifestyle modifications and
      eviction of any additive cardiovascular risk are the first step before
      considering treatment. Statins may be introduced between age 10 to 50 depending
      on the severity of the familial history, the elevation of the lipid values and
      the presence of vascular dysfunction.

PMID- 22471111
TI  - [Should we screen and treat subclinical hypothyroidism?].
AB  - Subclinical hypothyroidism, defined as an elevated thyroid stimulating hormone
      and normal thyroxine level, is common with aging, particularly after 65 years
      old. This condition is potentially associated with important consequences, such
      as cardiovascular diseases and cognitive disorders. So far, indications for
      screening and thyroxine replacement therapy are still controversial. In this
      review, we examine the data on those risks and the potential benefits of the
      treatment. We also present a large European randomized clinical trial that should
      clarify this controversy, in order to improve clinical care of patients with
      subclinical hypothyroidism and to give reliable data on maintaining good health
      among the elderly.

PMID- 22471112
TI  - [Lipid-lowering treatment and liver dysfunction].
AB  - Statins are a cornerstone of cardiovascular prevention. Their utilization is
      mostly well tolerated and safe: the commonly reported hepatic adverse effect is
      an asymptomatic, reversible and dose-related increase in liver enzyme levels
      occurring in case of risks factors. Statins do not worsen liver function in most
      patients with chronic liver diseases, including nonalcoholic fatty liver disease
      and hepatitis C, and might be used cautionsly. However, decompensated cirrhosis
      and acute liver failure are contraindications for statins. Routine hepatic
      biochemical test monitoring is questioned and might be performed in following
      situations: chronic liver diseases, alcohol consumption, drug interactions. Other
      causes should be screened and treatment be temporarily withheld in case of an ALT
      elevation > 3 times the upper limit of the norm.

PMID- 22471113
TI  - [Sucrose, glucose, fructose consumption: what are the impacts on metabolic
      health?].
AB  - There is growing evidence that consumption of added sugars play a role in the
      recent increase of metabolic diseases: 1) The intake of derived caloric
      sweeteners has increased in conjunction with rising prevalence of obesity; 2)
      Epidemiologic data and experimental studies show a positive correlation between
      sugar, fructose or sweetened beverages consumption and component of the metabolic
      syndrome. Several questions regarding effect of natural sugars on health are not
      answered yet, particularly the interactions between sugar intake and environment
      factors including ethnicity background and physical activity. Only Interventional
      studies will elucidate if there is a causal relation between sugar intake and
      metabolic diseases in humans.

PMID- 22471114
TI  - [Are genetic tests useful for cardiovascular prevention?].
AB  - Recent progresses in genetics have opened new avenues to further our
      understanding of the pathophysiological mechanisms underlying cardiovascular
      disease, raising, new expectations in the field of personalized medicine. Genetic
      tests may have a high predictive value for rare monogenic diseases. The situation
      is very different for common polygenic diseases, such as myocardial infarction,
      type 2 diabetes or stroke. The results from recent genome-wide association
      studies have provided useful information for research, but have not yet been
      proven to be clinically useful. It is therefore currently not recommended to
      conducted genetic testing to guide cardiovascular prevention neither in clinical
      nor in public health settings.

PMID- 22471115
TI  - [New european guidelines for dyslipidemia].
AB  - Lifestyle changes should be considered before anything else in patients with
      dyslipidemia according to the new guidelines on dyslipidemias of the European
      Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). The
      guidelines recommend the SCORE system (Systematic Coronary Risk Estimation) to
      classify cardiovascular risk into four categories (very high, high, medium or low
      risk) as the basis for treatment decisions. HDL cholesterol, which is inversely
      proportional to cardiovascular risk, is included to the total risk estimation. In
      addition to calculating absolute risk, the guidelines contain a table with the
      relative risk, which could be useful in young patients with a low absolute risk,
      but high risk compared to individuals of the same age group.

PMID- 22471116
TI  - [Short and medium-term effectiveness of the emergency-crisis treatments for
      couples and families: results and perspectives].
AB  - From 2007 to 2010, the emergency-crisis unit of the Couple and Family
      Consultation Unit -UCCF (West Psychiatric Service, Prangins Psychiatric Hospital,
      Psychiatric Department of CHUV) has carried out a research about the relevance
      and usefulness of emergency-crisis, systemic-oriented treatments, for deeply
      distressed couples and families. Besides epidemiologic data, we present results
      demonstrating the efficiency of those treatments, both at short-term and at a one
      year's range. The global impact of such treatments in terms of public health, but
      also economical issues, make us believe that they should be fully included in the
      new trend of psychiatric ambulatory care, into the social net.

PMID- 22471117
TI  - [Lower limb luxations: knowing them and treating them].

PMID- 22471118
TI  - [Free movement of physicians: the postgraduate education should be clearly
      displayed].

PMID- 22471119
TI  - [Syria: medicine as a war weapon].

PMID- 22471120
TI  - [Preventing the dementia epidemic (1)].

PMID- 22471122
TI  - [Human embryo, republican president].

PMID- 22471123
TI  - [When physicians waged war against ovaries (3)].

PMID- 22471124
TI  - [Towards an oneiric civilization?].

PMID- 22471125
TI  - [Observation of clinical efficacy of acupuncture for cerebral vasospasm after
      embolization of ruptured aneurysms].
AB  - OBJECTIVE: To observe the improvement of acupuncture in cerebral vasospasm (CVS)
      after embolization of ruptured aneurysms. METHODS: Sixty cases were randomly
      divided into two groups, an acupuncture-medication group and a conventional
      treatment group, 30 cases in each one. The cases of CVS in conventional treatment
      group were treated with Nimodipine. In acupuncture-medication group, on the basis
      of the treatment as conventional treatment group, Baihui (GV 20) and Fengchi (GB
      20) were selected as the main acupoints in the treatment of CVS. The treatment
      lasted for 3 weeks. Hunt-Hess scale for the standard assessment was adopted to
      determine the severity of disease before and after treatment and compare the
      efficacy between two groups. The transcranial Doppler (TCD) was conducted on the
      1st, 4th, 7th, 10th, 14th and 21st days successively after operation, and the
      average flow velocity of 3 pairs of vessels (ACA, MCA, and PCA) was recorded. CT
      perfusion (CTP) was taken to test cerebral blood flow (CBF), cerebral blood
      volume (CBV) and mean transit time (MTT) on the 1st, 7th, 14th and 21st days
      successively. RESULTS: The improvement of Hunt-Hess scale in acupuncture
      medication group was superior to that in conventional treatment group (P < 0.05).
      The analysis of variance (ANOVA) was adopted in the comparison of ACA, MCA, PCA,
      CBF, CBV and MTT between two groups. The results showed that the therapy in
      either group achieved the effect on CVS (all P < 0.05). But, the improvements in
      the above mentioned indices in acupuncture-medication group were superior to
      those in conventional treatment group (all P < 0.05). CONCLUSION: Acupuncture at
      Baihui (GV 20) and Fengchi (GB 20) down-regulates the peak values or upregulates
      the valley values. It releases the peak of CVS effectively, improves the clinical
      prognosis significantly and is the effective therapy for CVS after subarachnoid
      hemorrhage.

PMID- 22471126
TI  - [Effects of stimulating in the cavum concha on glucometabolism in patients with
      diabetes].
AB  - OBJECTIVE: To explore the intervention effect of the auricular stimulator in the
      cavum concha for diabetes. METHODS: Forty-five cases were treated with auricular
      simulator in the cavum concha for 30 min, once daily for consecutive 3 months.
      The changes of the fasting plasma glucose (FBG), blood glucose load after 2-hour
      75 g oral glucose tolerance test (P2 BG)and glycosylated hemoglobin (HbA1c) were
      compared before and after treatment. RESULTS: The level of the HbA1c was
      obviously decreased (P < 0.05, P < 0.01), and there were also statistically
      significant differences in FBG and P2 BG after the treatment (P < 0.05, P <
      0.01). CONCLUSION: With the auricular stimulator, the stimulation in the cavum
      concha is benefit for the improvement of HbA1c of the diabetes.

PMID- 22471127
TI  - [Clinical observation of acupoint sticking therapy with Xiongbai Qianlie powder
      in the treatment of type III prostatitis syndrome].
AB  - OBJECTIVE: To compare the efficacy difference between acupoint sticking therapy
      and the combined therapy of retention-enema and millimeter-wave radiation in the
      treatment of type III prostatitis syndrome. METHODS: Seventy-two cases were
      randomized into an acupoint sticking therapy group (group A, 36 cases) and an
      enema group (group B, 36 cases). The acupoint sticking therapy with Xiongbai
      Qianlie powder was applied to Ciliao (BL 32), Zhongji (CV 3), Guanyuan (CV 4),
      Huiyin (CV 1) and Changqiang (GV 1) in group A. The retention-enema with Ruyi
      Jinhuang powder plus millimeter-wave radiation at the prostatic region was used
      in group B. Eight treatments made one session. Totally, 2 sessions of treatment
      were required. The score of the symptoms of chronic prostatitis (NIH-CPSI) and
      the efficacy were observed. RESULTS: Of 36 cases in group A, 5 cases were dropped
      off, 13 cases remarkably effective, 17 cases effective and 1 case failed; the
      total effective rate was 96.8% (30/31). Of 36 cases in group B, 7 cases were
      dropped off, 7 cases remarkably effective, 17 cases effective and 5 cases failed;
      the total effective rate was 82.7% (24/29). The efficacy in group A was much
      better (P < 0.05). After the treatment, the score of NIH-CPSI was reduced
      obviously in either group (both P < 0.01). The result in group A was much better
      than group B (P < 0.05). CONCLUSION: The acupoint sticking therapy with Xiongbai
      Qianlie San achieves a good efficacy on type III prostatitis syndrome and its
      efficacy is superior to the retention-enema plus millimeter-wave radiation
      therapy.

PMID- 22471128
TI  - [Observation on therapeutic effect of chronic fatigue syndrome treated with
      coiling dragon needling and moving cupping on back].
AB  - OBJECTIVE: To compare the differences of therapeutic effect of chronic fatigue
      syndrome treated with the combined therapy of coiling dragon needling and cupping
      on back and the western medicine therapy with Prednisone. METHODS: Seventy-two
      cases were randomly divided into an acupuncture and cupping group (37 cases) and
      a Prednisone group (35 cases). In acupuncture and cupping group, Jiaji (EX-B 2)
      points of T1--L5 were applied with coiling dragon needling (once a day), combined
      with moving cupping on back (once every two days); in Prednisone group,
      Prednisone tablets were orally taken for 10 mg at 8:00 am. Seven days made one
      course, and 2 courses were carried on totally. FS-14 scale and BELL's chronic
      fatigue syndrome integral table were applied to evaluate the fatigue degree of
      patients before and after treatment, and the therapeutic effects of both groups
      were compared. RESULTS: After one course of treatment, the BELL's scores of both
      groups were obviously improved (both P < 0.01), but there was no significant
      difference between groups (P > 0.05); after two courses of treatment, the BELL's
      score in acupuncture and cupping group improved more obviously than that in
      Prednisone group, and the total effective rate of 91.9% (34/37) in acupuncture
      and cupping group was superior to that of 71.4% (25/35) in Prednisone group (P <
      0.05). CONCLUSION: The therapeutic effect of chronic fatigue syndrome treated
      with coiling dragon needling and moving cupping on back is positive, superior to
      that of Prednisone with oral administration.

PMID- 22471129
TI  - [Case of mongolism].

PMID- 22471130
TI  - [Twenty-two cases of short bowel syndrome treated with acupuncture].

PMID- 22471131
TI  - [Clinical observation on cervical spondylosis of neck type treated with
      acupuncture at original and terminal points of trapezius].
AB  - OBJECTIVE: To compare the differences of therapeutic effect of cervical
      spondylosis of neck type treated with acupuncture at starting and ending points
      of trapezius and the Jiaji (EX-B 2) points. METHODS: Sixty cases of cervical
      spondylosis of neck type were randomly divided into an observation group and a
      control group, 30 cases in each group. In observation group, the acupoints
      related with starting and ending points of trapezius, such as Tianzhu (BL 10),
      Fengchi (GB 20), Quyuan (SI 13), Jugu (LI 16) and Ashi were punctured; in control
      group, Jiaji (EX-B 2) points of neck were punctured. The treatments were applied
      5 times a week and 2 weeks made one course. The international simplified McGill
      scale was adoped to assess the scores of Pain Rating Index (PRI), Visual Analogue
      Scale (VAS) and Present Pain Intensity (PPI) before treatment and after one
      course treatment, and the therapeutic effects were measured. RESULTS: After
      treatment, all the scores were obviously reduced in both groups: (all P < 0.01),
      and the PRI-sensory subscore, PRI-affective subscore and total score in
      observation group reduced more obviously than those in control group, and there
      were statistically significant differences between groups (all P < 0.01). There
      were no statistically significant differences between groups in VAS and PPI score
      (both P > 0.05). The total effective rate of 96.7% (29/30) in observation group
      was superior to that of 70.0% (21/30) in control group (P < 0.01). CONCLUSION:
      The therapeutic effect of cervical spondylosis of neck type treated with
      acupuncture at the starting and ending points of trapezius is positive, which is
      better than that of acupuncture at the Jiaji (EX-B 2) points.

PMID- 22471132
TI  - [Parkinson's disease combined with overactive bladder syndrome treated with
      acupuncture and medication].
AB  - OBJECTIVE: To evaluate the therapeutic effect of Parkinson's disease combined
      with overactive bladder syndrome (GAB) treated with combined therapy of oral
      administration of Tolterodine with low dose and electroacuponcture. METHODS:
      Sixty cases of Parkinson's disease combined with GAB were randomly divided into a
      combined acupuncture and medication group (group A) and a medication group (group
      B), 30 cases in each group. In both groups, Madopar basic doses were same, and
      anticholinergic agents such as Artane were stopped. In group A, Tolterodine was
      orally taken for 1 mg, twice a day; Baihui (GV 20), Sishengcong (EX-HN 1) and
      Yintang (EX-HN 3) were punctured with electroacupuncture, once a day. In group B,
      Tolterodine was orally taken for 2 mg, twice a day. After 6 weeks, the changes of
      urination and UPDRS III scores were observed, and the adverse reactions were
      recorded in both groups. RESULTS: After treatment, the frequency of average
      urination of 24 hours, frequency of incontinence of 24 hours and average urine
      volume at a time were obviously improved (all P < 0. 01), of which, the above
      items in group A were superior to those in group B (all P < 0. 05) the UPDRSIII
      score in group A was superior to that in group B (P < 0.05). The adverse
      reactions in group A were less than those in group B. CONCLUSION: The therapeutic
      effect of Parkinson' s disease combined with GAB treated with combined therapy of
      Tolterodine with low dose and electroacupuncture is superior to that of complete
      dose of Tolterodine with oral administration, with less adverse reactions. And it
      also can improve the motor symptom of Parkinson's disease patients.

PMID- 22471133
TI  - [Anti-depression effect of acupunctrue and moxibustion based on SSRIs
      medication].
AB  - OBJECTIVE: To verify the anti-depression effect of acupuncture and moxibustion
      based on the medication with selective serotonin reuptake inhibitors (SSRIs).
      METHODS: Eighty cases of depression were randomly divided into an acupuncture
      moxibustion-medication group (25 cases), an acupuncture-medication group (25
      cases) and a medication group (30 cases). SSRIs medication was administered in
      all of the three groups. Complementarily, in acupuncture-moxibustion-medication
      group, the needling technique of qi conduction in the Governor Vessel was applied
      to Baihui (GV 20), Fengfu (GV 16), Dazhui (GV 14), etc. Additionally, mild
      moxibustion was added at Dazhui (GV 14) and Baihui (GV 20). In acupuncture
      medication group, acupuncture for qi conduction in the Governor Vessel was only
      adopted. Hamilton Depression Scale (HAMD) was used for the evaluation of the
      total score, the score of each factor before and after treatment separately, and
      the therapeutic effects were observed among 3 groups. RESULTS: Compared with
      medication group, the scores of the factors as retardation, sleep, and
      anxiety/somatization, as well as the total score were all apparently improved in
      the other two groups (P < 0.05, P < 0.01). Compared with acupuncture-medication
      group, the scores of sleep and cognition factors as well as the total score in
      HAMD were much improved in acupuncture-moxibustion-medication group (P < 0.05, P
      < 0.01). The remarkable effective rates were 100.0% (25/25), 84.0% (21/25) and
      56.7% (17/30) in the three groups separately, in which, the result in acupuncture
      moxibustion-medication group was superior to acupuncture-medication group (P <
      0.05), and the results of these two groups were superior to medication group
      (both P < 0.01). CONCLUSION: Either acupunctrure or moxibustion has a definite
      anti-depression effect based on SSRIs medication, but the coordination of
      acupuncture and moxibustion achieves a superior efficacy as compared with simple
      acupuncture therapy.

PMID- 22471134
TI  - [Case of abdominal distension and foul breath].

PMID- 22471135
TI  - [Observation on therapeutic effect of migraine treated with medicated threads
      moxibustion of Zhuang nationality].
AB  - OBJECTIVE: To observe the therapeutic effect and adverse reaction of migraine
      treated with medicated threads moxibustion of Zhuang nationality. METHODS: One
      hundred and twenty cases of migraine were randomly divided into a medicated
      threads group and a medication group. Sixty cases were treated with medicated
      threads moxibustion of Zhuang nationality in medicated threads group, and 60
      cases were treated by Ergotamine and Caffeine tablets with oral administration in
      medication group. All the cases in both groups were continuously treated for 30
      days. The score changes of headache and the adverse reactions of patients were
      observed, and the therapeutic effects were evaluated. RESULTS: The scores of
      headache after treatment were lower than those before treatment in both groups,
      indicating the statistically significant differences (both P < 0.05); compared
      with the scores of headache between both groups after treatment, there was no
      significant difference (P > 0.05). The total effective rate in medicated threads
      group was 93.3% (56/60) and 90.0% (54/60) in medication group, and there was no
      significant difference in comparison of therapeutic effects of both groups (P >
      0.05). There was no any adverse reaction in medicated threads group; the symptoms
      such as flushing and discomfort of upper abdomen, etc. appeared in 20 cases in
      medication group. CONCLUSION: The therapeutic effect of migraine treated with
      medicated threads moxibustion of Zhuang nationality is significantly effective,
      and there is no any adverse reaction.

PMID- 22471136
TI  - [Comprehensive therapy for 53 cases of qi-stagnation constitution].

PMID- 22471137
TI  - [Comparative study of heat-sensitive moxibustion in the treatment of knee
      osteoarthritis].
AB  - OBJECTIVE: To verify the clinical efficacy of heat-sensitive moxibustion in
      treatment of knee osteoarthritis (KOA). METHODS: Sixty cases of KOA were randomly
      divided into a heat-sensitive moxibustion group and a conventional moxibustion
      group, 30 cases in each one. Dubi (ST 35), Yanglingquan (GB 34), Zusanli (ST 36)
      and Heding (EX-LE 2) on the affected side were selected in two groups. In heat
      sensitive moxibustion group, the techniques of circling moxibustion, sparrow
      pecking moxibustion, moving moxibustion and mild moxibustion were applied. In
      conventional moxibustion group, the mild moxibustion was used, 2 to 3 cm far from
      the skin of the acupoints selected. Lysholm scale for the assessment of knee
      joint function was adopted to evaluate the efficacy. The scores of joint pain,
      morning stiffness, joint swelling and walking ability were compared before and
      after treatment in two groups. RESULTS: The scores of joint pain, morning
      stiffness, joint swelling and walking ability after treatment were all apparently
      improved as compared with those before treatment in either group (all P < 0.05).
      The improvement in the above-mentioned indices in heat-sensitive moxibustion
      group was much more apparent as compared with that in conventional moxibustion
      group (all P < 0.01). The effective rate was 90.0% (27/30) in heat-sensitive
      moxibustion group and was 73.3% (22/30) in conventional moxibustion group. The
      effective rate in heat-sensitive moxibustion group was obviously superior to that
      in conventional moxibustion group (P < 0.01). CONCLUSION: The efficacy of heat
      sensitive moxibustion is superior to that of conventional moxibustion in the
      treatment of KOA. This therapy can more significantly improve the symptoms and
      physical signs of the patients with KOA.

PMID- 22471138
TI  - [Efficacy observation of xerophthalmia treated with acupuncture of warming
      promotion needling technique].
AB  - OBJECTIVE: To observe the differences in the efficacy on xerophthalmia treated
      with the needling technique for warming-promotion at Fengchi (GB 20) as the main
      acupoint in comparison with the conventional needling technique. METHODS: Thirty
      cases were randomly divided into a warming-promotion needling group (n = 15) and
      a routine needling group (n = 15). In warming-promotion needling group, the
      needling technique for warming-promotion was applied to Fengchi (GB 20).
      Additionally, the local and distal acupoints [such as the point beneath Cuanzu
      (BL 2), Neiguan (PC 6), Guangming (GB 37), Taichong (LR 3), Fulio (KI 7) and
      Sanyinjiao (SP 6)], as well as the scalp acupuncture (bilateral supraoccipital
      lateral line and supraoccipital midline) were selected and stimulated with even
      needling technique by rotating the needle. In routine needling group, the
      acupoints were same as warming-promotion needling group and were stimulated with
      even-needling technique by rotating the needle. After 2 sessions of treatment,
      the efficacy, tear secretion volume and the total score of symptoms were compared
      between two groups. RESULTS: The total effective rate was 86.7% (13/15) in
      warming-promotion needling group, which was superior to 66.7% (10/15) in routine
      needling group (P < 0.05). After treatment, the tear secretion volume and the
      total score of symptoms were all apparently improved in two groups (all P <
      0.05), in which, the improvement in warming-promotion needling group was much
      obvious (all P < 0.05). CONCLUSION: The therapeutic effect of warming-promotion
      needling technique is apparently superior to that of conventional one.

PMID- 22471139
TI  - [Clinical application on innovated burning rush moxibustion].
AB  - On the basis of traditional burning rush moxibustion, Dr. DIAO Ben-shu innovated
      moxibustion device and technique. Many different herbal medicines are selected to
      prepare moxa stick, a matchstick in size. After ignited, this stick burns swiftly
      and directly at acupoint in human body so that the meridian qi circulation is
      invigorated and the disease is prevented and treated. Diao's moxa stick technique
      is characterized as scientific preparation, safe and simple operation and quick
      efficacy. A better efficacy is achieved in clinical practice. The operation and
      clinical application of Diao's moxa stick technique as well as the theory of
      moxibustion are discussed and analyzed in this paper.

PMID- 22471140
TI  - [Acupotomy-relaxing for 18 cases of heart disease due to cervical spondylosis].

PMID- 22471141
TI  - [Effect of electroacupuncture at "Fenglong" (ST 40) on rats with hyperlipidemia
      and its mechanism].
AB  - OBJECTIVE: To explore the mechanism of electroacupuncture(EA) at "Fenglong" (ST
      40) in hyperlipidemia (HLP) rats. METHODS: Forty health SD rats were randomly
      divided into a normal control group (group A), a high fat forage feed group
      (group B) and a high fat forage feed treatment group (group C), a high fat forage
      + normal forage feed group (group D) and a high fat forage + normal forage feed
      treatment group (group E), eight rats in each group. EA was applied at "Fenglong"
      (ST 40) for the rats in group C and group E, once daily. After treatment of 30
      days, blood lipid levels of rats, including total cholesterol (TC), triglyceride
      (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
      cholesterol (HDL-C) in plasma were tested. Real time polymerase chain reaction
      (RT-PCR) and Western Blotting were applied to detect the gene expression changes
      of the contents of ATP-binding cassette transporter A1 (ABCA1), peroxisome
      proliferator-activated receptor alpha (PPARalpha), liver X receptor alpha (LXR
      alpha) and retinoid X receptor alpha (RXR-alpha) in liver tissue of rats.
      RESULTS: Compared with group A, the contents of TC, LDL-C were significantly
      elevated in group B and group D (all P < 0.01); compared with group B, above
      indices were significantly decreased in group D (all P < 0.01). After the
      treatment of EA at "Fenglong"(ST 40), the contents of TC, LDL-C were
      significantly decreased (all P < 0.01), and the contents of TG, HDL-C did not
      change obviously (all P > 0.05). Compared with group A, the mRNA and protein
      contents of ABCA1, PPARalpha, LXR-alpha and RXR-alpha were decreased obviously in
      group B and group D (all P < 0.01). But compared with group B, the above indices
      were decreased in the group D. There were signficantly increasing in the protein
      content of ABCA1, PPARalpha, RXR-alpha and LXR-alpha mRNA after the treatment of
      EA (all P < 0.05). CONCLUSION: EA at "Fenglong" (ST 40) has some therapeutic
      effect on decrease the content of TC, LDL-C in rats of hyperlipemia and improve
      the gene expression of ABCA1, PPARalpha, LXR-alpha and RXR-alpha mRNA so as to
      promote reverse cholesterol transport.

PMID- 22471142
TI  - [Effect of moxibustion on motility, absorption and content of ATP in small
      intestine of spleen-deficiency rats].
AB  - OBJECTIVE: To explore the mechanism of reinforcing function of moxibustion to
      spleen-stomach. METHODS: Forty healthy Sprague Dawley rats were randomly divided
      into 4 groups: group A (blank group), group B (model group), group C (moxibustion
      group) and group D (herbs group). The rat model of spleen-deficiency was
      established by intragastric administration with 200% Dahuang (Rhubarb) infusion.
      The rats in group A and B, and D served as the blank control, model, and Sijunzi
      decoction group respectively, while those in group C received moxibustion at
      "Zusanli" (ST 36), "Zhongwan" (CV 12), "Guanyuan" (CV 4), "Pishu" (BL 20) and
      "Weishu" (BL 21), etc. The common symptoms and intestinal propulsive rate were
      observed. The content of I-xylose in serum was detected by phloroglucinol method.
      Colorimetry method was used to detected content of ATP in jejunum tissues.
      RESULTS: Compared with group A, the symptom score in group B was increased
      significantly (both P < 0.01), while the intestinal propulsive rates, the content
      of D-xylose in serum and ATP in jejunum tissues were decreased significantly (P <
      0.05, P < 0.01). Compared with group B, the symptom score in group C and D was
      decreased significantly (both P < 0.01), while the intestinal propulsive rates,
      the content of D-xylose in serum and ATP in jejunum tissues were increased
      significantly (P < 0.05, P < 0.01). There were no significant difference between
      group C and D (P > 0.05). CONCLUSION: Moxibustion at "Zusanli" (ST 36) etc. could
      relieve symptoms of spleen-deficiency, enhance motility and absorption functions
      of small intestine and improve metabolism of small intestine. The efficacy is
      equal to administration of Sijunzi decoction.

PMID- 22471143
TI  - [MA Shao-qun's clinical experience of warm moxibustion for the liver diseases].
AB  - To summarize MA Shao-qun's clinical experience of warm moxibustion for the liver
      diseases. The warm moxibustion was put to use by MA Shao-qun to treat many
      diseases, including hepatitis, cirrhosis and liver functional disorder. Under the
      human-oriented theory, he focuses on regulating the whole function of the body
      and tonifying the original qi to increase physical fitness and avoid illness.
      Besides, he is good at the combination of multi-acupoints for long-term and
      circulating moxibustion treatment, and also pays attention to nourishing the
      spleen-stomach, adjusting the fu-qi and resolving the dampness in the body.

PMID- 22471144
TI  - [Professor XIAO Ji-fang's idea on acupuncture-moxibustion ].
AB  - Professor XIAO Ji-fang, an experienced practitioner of Chinese medicine of
      Guangxi, is famous for his medical ethics, wide range of studies, comprehensive
      understanding of the classics, innovation, as well as u nique academic ideas. He
      focuses on mind-regulating in acupuncture and pulse diagnosis. At the same time,
      differentiation of syndromes, diseases and meridians are emphasized. The
      combination of acupuncture and moxibustion and integration of acupuncture and
      medicine are promoted. He is especially skilled at slow twisting needle
      insertion, Taiji needling therapy, scalp acupuncture and moxibustion with a herb
      prepared thread of Zhuang nationality, which all achieve remarkable effects.

PMID- 22471145
TI  - [Differences of clinical trails on domestic and international treatment of knee
      osteoarthritis with acupuncture].
AB  - Literatures on knee osteoarthritis treated by acupuncture both in China and
      abroad published in the mainstay periodicals in recent 10 years were selected,
      and analyses were done in the following aspects: (1) Randomization, (2) Control
      group, (3) Sample size, (4) Intervention measurements, (5) Intervention periods,
      (6) Evaluation on therapeutic effects, (7) Follow-up assessment, (8) Adverse
      effects, (9) Ratio of the lost case. The result indicates that differences can
      still be found on the trial designation in China and abroad. The domestic
      research design should be more comprehensively and strictly.

PMID- 22471146
TI  - [Research on needle-acupointomics].
AB  - The concept of needle-acupointomics should be clarified initially in order to
      discuss the relative researches. The comprehension can be deepened through the
      aspects of researching methods, content and goals. Proper researching model and
      analysis method should be selected so as to bring the advantages of the ancient
      acupuncture literatures, case records and clinical experiences of famous
      physicians into full play. Only in this way can the domestic needle acupointomics
      studies achieve a breakthrough.

PMID- 22471147
TI  - [Clinical application of the penetrating needling technique from Yemen (TE 2) to
      Zhongzhu (TE 3)].
AB  - The penetrating technique of acupuncture from Yemen (TE 2) to Zhongzhu (TE 3)
      acts on the extraordinary effect of promoting Shaoyang meridian qi. The technique
      is specially good for heat pattern/syndrome of the triple energizer and it is
      commonly used in the treatment of common cold, high fever, anhidrosis in heat
      pattern/syndrome, migraine, redness, swelling and pain of the eye, tinnitus, ear
      pain, swelling and pain of the teeth, ulcers in the mouth and tongue, sore
      throat, neck rigidity, etc. In the manipulation, the needle is inserted from
      Yemen (TE 2), going obliquely upward along the metacarpal interspace to Zhongzhu
      (TE 3). With this technique, the Ying-spring and Shu-stream acupoints can be
      stimulated simultaneously with one needle. This method is characterized as less
      acupoints, exquisite needling, strong sensation, easy and safe manipulation,
      remarkable immediate effect and high curative rate of single treatment. Hence, it
      is worthy of application in clinical practice.

PMID- 22471148
TI  - [Analysis of palpation laws of muscle meridian focus on knee osteoarthritis].
AB  - OBJECTIVE: To explore the distribution regulars of proximal and distal focus of
      muscle meridian regions in knee osteoarthritis patients. METHODS: Seven hundred
      and sixty-five knees were selected in 516 cases of knee osteoarthritis. Under the
      guidance of muscle meridian theory, with the anatomical features of muscle
      meridian focus, the frequency and the location where the proximal and distal
      focus of muscle meridian regions appeared were calculated by palpation. RESULTS:
      Of all the points, 11 835 points of proximal focus of muscle meridian regions
      were found out by palpation, and 9455 points of distal focus of muscle meridian
      regions were found out. The percentages of the frequency that the focus of muscle
      meridian of Foot-Yangming, Foot-Taiyang, Foot-Shaoyang and three foot Yin
      meridians appeared at proximal points of knee were 37.1% (4388/11 835), 34.9%
      (4127/11 835), 9.5% (1129/11 835) and 18.5% (2191/11 835) respectively; and the
      percentage of the frequency that the focus of muscle meridian appeared at distal
      points of knee were 24.7% (2333/9455), 25.2% (2380/9455), 28.5% (2700/9455) and
      21.6% (2042/9455). CONCLUSION: The proximal and distal focus of muscle meridian
      in knee osteoarthritis patients are closely related with anatomy structure and
      biomechanical characteristics; the distribution regulars of focus of muscle
      meridians study provides evidence for the selection of effective treatment points
      from different clinical acupuncture therapies.

PMID- 22471149
TI  - [Background and process of the formation of Chengjiang acupuncture school].
AB  - The times background and the forming process of Chengjiang Acupuncture School
      which composed mainly of Mr. CHENG Dan-an and his followers are studied in this
      paper. It is concluded that the forming of Chengjiang Acupuncture School is based
      on the kindness of its founder and his followers to the poor and patients, as
      well as their devotion to acupuncture-moxibustion which are characterized by
      cheap, convenient and effective features. The development and growth of the
      school profited from new China's health policy which attached equal importance to
      both Chinese and western medicines. The school's formation and development
      process highlighte its features of firm convictions, courage when facing
      difficulties and keeping pace with the times.

PMID- 22471150
TI  - [Study on medical records of acupuncture-moxibustion in The Twenty-four
      Histories].
AB  - Through the combination of manual retrieval and computerized retrieval, medical
      records of acupuncture-moxibustion in The Twenty-Four Histories were collected.
      Acupuncture cases from the Spring and Autumn Period (770-476 B.C.) to the end of
      the Ming Dynasty (1368-1644)were retrieved. From the medical records of
      acupuncture-moxibustion in Chinese official history books, it can be found that
      systematic diseases or emergent and severe diseases were already treated by
      physicians with the combination of acupuncture and medicine as early as in the
      Spring and Autumn Period as well as the Warring States Period(475-221 B.C.). CANG
      Gong, a famous physician of the Western Han Dynasty (206 B. C.-A. D. 24), cured
      diseases by selecting points along the running courses of meridians where the
      illness inhabited, which indicates that the theory of meridians and collaterals
      was served as a guide for clinical practice as early as in the Western Han
      Dynasty. Blood letting therapy, which has surprising effect, was often adopted by
      physicians of various historical periods to treat diseases. And treatment of
      diseases with single point was approved to be easy and effective.

PMID- 22471151
TI  - [Case of childhood dermatomyositis].

PMID- 22471152
TI  - [Acupuncture-moxibustion and mitogen-activated protein kinase signal transduction
      pathways].
AB  - The Literatures on mechanism of acupuncture from the aspect of mitogen-activated
      protein kinase (MAPK) signal transduction pathways are analyzed in this paper.
      And the result shows that many acupuncture effects are closely related with the
      regulation of MAPK signal transduction pathway. However, the current studies only
      cover limited aspects, and there problems still existed in the experiment
      designation. Acupuncture and electroacupuncture are often adopted for the
      treatment group, while moxibustion is not applied for most of them. There are not
      unified wave model, frequency and stimulation period for electroacupuncture. And
      the studies still remain in simple confirmation and proper inference. In the
      future, the domain of researches should be further wid ened and the experiment
      designation further perfected. Therefore, the therapeutic effect of acupuncture
      in clinic will be greatly improved through researches on MAPK signal transduction
      pathway and the production mechanism of acupuncture effect.

PMID- 22471153
TI  - [Oral cancer awareness of physicians and dentists in the Israeli army].
AB  - Oral cavity squamous cell carcinoma (OSCC) accounts for 2-3% of all body
      malignancies. The aim of this study was to asses the knowledge and awareness of
      general practitioners and the dental practitioners in the Israeli army to OSCC.
      Israeli's defense force's medical corps's dentists and physicians took part in
      this study. A questionnaire was constructed to obtain information about:
      Demographics, Knowledge concerning signs, symptoms and risk factors of oral
      cancer, Attitude on referral and knowledge transfer to patients, Satisfaction and
      need for farther guidance on the subject. The questionnaire was sent via E mail
      to all army physicians and dentists. 80% of the dentists and 35% of the
      physicians replayed. According to our study there is a knowledge gap between
      physicians and dentists in several areas: Physicians showed less awareness to the
      disease therefore, are less likely to do regular oral examinations. Physicians
      had less information about risk factors (especially alcohol) and are less likely
      to pass information about the risk factors to their patients. Suspicious lesions
      in the oral cavity were less recognized as such by physicians. This study shows
      the need to strengthen physicians' knowledge and awareness concerning oral
      cancer.

PMID- 22471155
TI  - [Cytomegalovirus (CMV)--a frequently encountered virus].

PMID- 22471154
TI  - [Materials and technologies for fabricating denture bases].
AB  - The materials and technologies for fabrication of denture bases have developed
      during the last 150 years. The requirements of the ideal material are versatile
      and include functional, physical and esthetical demands. The current manuscript
      classifies denture base materials according to their chemical characteristics
      into polymers, reinforced polymers and light cured polymers. Poly Methyl
      Metacrylate (PMMA) was developed 70 years ago, and is still the major material
      for fabrication of denture bases due to its esthetic characteristics, high
      processing and polishing abilities, relining and rebasing possibility and low
      cost. The main disadvantages of PMMA are its dimensional changes during
      polymerization, porosity and allergic/cytotoxic effects. PMMA may be reinforced
      by metal, polyethylene or glass fibers. Other materials used for fabrication of
      denture bases are Nylon and Urethane dimethacrylate. Their advantages are better
      esthetics, low modulus of elasticity and reduced cytotoxicity. This review
      presents the advances in materials and techniques used for denture bases, the
      different materials, their advantages and disadvantages, the chemical reactions
      associated with their production, and their allergic and cytotoxic side effects.

PMID- 22471156
TI  - [Cytogenetics of oral solid tumors].
AB  - The tumorigenesiss of oral solid tumors is still uncertain. The underlying
      mechanisms of epithelial or connective tissue proliferation are not yet fully
      understood. Also, the transformation of a benign tumor into malignant is obscure.
      Cytogenetics is the study of chromosome number and structure using a light
      microscope. Human chromosome nomenclature is based on An International System for
      Human Cytogenetic Nomenclature (ISCN). The normal human somatic cells have 46
      chromosomes, including 22 pairs of autosomes and two sex chromosomes, XX in
      female and XY in male. The chromosome abnormalities can be numerical and
      structural. Both types can occur concurrently. Numerical abnormalities involve
      the loss and/or gain of a whole chromosome and can include both autosomes and sex
      chromosomes. Cells which have lost a chromosome are categorized as a monosomy,
      while those with an extra chromosome are trisomy. Structural abnormalities
      include translocations, deletions, inversions and insertions. Cancer, in its
      various forms is a result of genetic changes. This concept comes from the finding
      of chromosomal abnormalities. These abnormalities may arise as a consequence of
      random replication errors; exposure to carcinogens; or damaged DNA repair
      process. In clinical oncology, the study of chromosome abnormalities in solid
      tumors provides valuable information for the diagnosis, evaluating treatment
      response of metastatic cancer, marker for prognosis and targeted therapy. In
      tumors which histologic features overlap, cytogenetics plays an important role
      for diagnosis. Cytogenetics has also been used to monitor the surgical margins of
      the resection in head and neck carcinoma, where the histology was not definitive.
      The present report will focus on the role of cytogenetics in the diagnosis and
      prognosis of benign and malignant oral solid tumors.

PMID- 22471157
TI  - [The relationship between celiac disease (CD) and dental problems].
AB  - With a prevalence of 1% in western populations, Celiac disease (CD) is one of the
      most common inflammatory disorders of the small intestine. CD is often assumed to
      have its onset in childhood, but it has recently been suggested that adults can
      also develop CD. Clinical manifestations vary according to age group: infants and
      young children present with diarrhea, abdominal distention, and failure to
      thrive, whereas adults that develop CD not only present with diarrhea, but also
      with silent manifestations such as anemia, osteoporosis, or neurological
      symptoms. In the small intestine of celiac disease patients, dietary wheat gluten
      and similar proteins in barley and rye trigger an inflammatory response. While
      strict adherence to a gluten-free diet induces full recovery in most patients, a
      small percentage of patients fail to recover. In a subset of these refractory
      celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte
      population develops into overt lymphoma. Celiac disease is strongly associated
      with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease
      development. mmunohistochemistry of the small intestine of patients shows villous
      atrophy, crypt hyperplasia, and elevated levels of intraepithelial lymphocytes
      (IELs). The only therapy until now is a gluten-free diet, which will normalize
      the clinical and histological manifestations and allows the patients to live an
      otherwise normal life. part of the symptoms are oral manifestations as dental
      enamel defects, aphthous ulcers and Atrophic Glossitis. The prevalence of caries
      in CD patiens is law as compared to the healthy population and in some cases the
      normal eruption sequence of the teeth was damaged. Part of the undiagnosed CD
      patients are among our patients and the enamel defects they present are
      misdiagnosed as tetracycline pigmentation or white spot lesions it is the
      practitioners responsibility to add CD as a possible cause to the findings and
      refer the patient to further examination. The case report in this paper presents
      a 47 years old female patient who was a patient in my practice for 25 years. When
      she became 40 she was diagnosed as CD and treated accordingly over the years
      enamel defects were treated conservatively. As the lesions became more frequent
      and unpredictable the patient demanded a full mouth solution that would restore
      both the functional and esthetical problems she had with her dentition. A full
      Porcelane Fused to Metal (PFZ) crowns were fabricated and the patient got a
      solution to both here demands. The crowns used were 3M Lava zirconia crowns and
      the case is presented as step by step sequence.

PMID- 22471158
TI  - [Immediate implant placement in endodontically infected sites: an alternative
      treatment for compromised teeth].
AB  - In certain clinical conditions when endodontic treatment is either impractical or
      unlikely to improve the previous results, tooth extraction and replacement with a
      dental implant becomes a viable alternative. Although the presence of active
      infection has long been considered a major contraindication to the insertion of
      implants immediately following tooth extraction, several articles assessing this
      treatment modality reported excellent and promising results. The aim of this
      literature review is to evaluate and discuss the clinical outcome of implants
      placed immediately following extraction in endodontically infected sockets. A
      Medline and EMBASE search was performed to identify articles published from 1966
      to 2010 using the keywords "dental implants", "immediate implant", "extraction
      socket", "infected teeth", "infected site", "infected socket". No restrictions
      were placed regarding the study design. Only clinical articles with at least 6
      months of follow-up were included. The available relevant literature concerning
      this topic was limited, and based on relatively low level of evidence study
      designs with limited follow-up periods. However, the data analysis of the
      selected articles showed that an immediate implant insertion in endodontically
      infected sites following tooth extraction and careful debridement of the socket,
      could be a predictable viable technique. Additional large scaled, well-designed
      studies are required in order to further assess the clinical applications of this
      treatment alternative.

PMID- 22471159
TI  - Who's afraid of whom?

PMID- 22471160
TI  - Tackling psychosis & depression with pharmacologic biomarkers.

PMID- 22471161
TI  - Incentives are good (except when they're bad).

PMID- 22471162
TI  - North Carolina PCMH's data offer promise, spur debate.

PMID- 22471163
TI  - Employers mostly in the dark when it comes to biologics.

PMID- 22471164
TI  - Less pain, lower costs: can integrative medicine do both?

PMID- 22471165
TI  - Clinical and economic outcomes of the Cincinnati Pharmacy Coaching Program for
      diabetes and hypertension.
AB  - PURPOSE: Value-based insurance designs (VBID) have been developed by health
      insurance companies and used by employers to allocate health care resources
      appropriately and to lower patients' out-of-pocket costs for services related to
      chronic conditions. The purpose of this study was to evaluate the effect of the
      Cincinnati Pharmacy Coaching Program (CPCP) on clinical and economic outcomes.
      The CPCP is a VBID implemented by Anthem Blue Cross & Blue Shield in Ohio. It
      provided tailored pharmacist-based educational services and financial incentives
      to participants. METHODS: This was a quasi-experimental pre/post longitudinal
      study in which patients were identified as they enrolled in the CPCP between Jan.
      1, 2008, and Dec. 31, 2009. Patients could participate in a Diabetes Coaching
      Program (DCP) or a Heart Healthy Coaching Program (HHCP). Control subjects were
      selected from patients who were invited but did not choose to participate.
      Control subjects were matched to intervention cohorts using propensity score
      matching. Clinical (blood pressure, lipid levels, and hemoglobin A1c) and
      economic (all-cause and disease-attributable) outcomes were evaluated using
      within-subject (pre-post) and between-subject comparison (intervention-control)
      design. RESULTS: A total of 607 patients were enrolled in intervention groups,
      and 557 control subjects were selected after matching. Significant reductions
      were found in blood pressure, lipid levels, and hemoglobin A1c after enrollment,
      and a significantly greater proportion of patients, compared with controls,
      achieved their clinical goals according to national guidelines in both programs.
      Hypertension-related cost trends were favorable for HHCP relative to the control
      cohort. Diabetes-related costs increased for all groups from pre- to post-index,
      largely driven by office visits and medication costs in the DCP and inpatient/ER
      visits in the control cohort. CONCLUSION: Results showed significant improvements
      in all diabetes- and hypertension-related clinical measures. This study shows the
      effect of a comprehensive VBID on the health of patients with chronic disease.

PMID- 22471166
TI  - Rules for evaluating biosimilars put applicants through hoops.

PMID- 22471167
TI  - An overview of National AIDS Control Program (NACP) with special reference to
      targeted intervention: issues & challenges.
AB  - Human Immune Deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS)
      has posed different set of challenges towards the country's growth and has also
      changed the strategic approach of Public Health for containing the further growth
      of the disease. HIV/AIDS is considered as more of a social problem than a medical
      problem alone. National AIDS Control Program (NACP) though its three phases have
      tried to design & implement evidence based strategies including Targeted
      Interventions (TI) based on the lessons learnt in the past. It has been a long
      journey for more than a decade which has brought innovations & effectiveness into
      the program and is showing some preliminary results in positive direction in
      limiting the HIV infection among HRGs. In the present communication few of the
      salient features of the entire approach and possible impacts in the future have
      been discussed.

PMID- 22471168
TI  - Genotype profiles of Mycobacterium avium subspecies paratuberculosis recovered
      from suspected and Crohn's disease patients in India.
AB  - Present study aimed to genotype Mycobacterium avium subspecies paratuberculosis
      (MAP) recovered from suspected and Crohn' s disease patients. A total of 32 MAP
      and DNA (directly from clinical samples) recovered from human origin were
      genotyped using IS 1311 PCR-REA. Isolates were cultured from stool, biopsies and
      blood clots of Crohn's disease patients, and stool samples of suspected (animal
      attendants, lab workers etc). Of the 32 MAP isolates belonging to 28 human
      beings, majority (84.3%) were genotyped as 'Bison type', while 21.7% were of
      'cattle' and none was 'sheep' genotype. Study first time reports distribution of
      'Cattle' and 'Bison type' 'genotypes in suspected and Crohn's patients on pilot
      scale in India. 'Bison type' genotype was predominant in the surveyed human
      population.

PMID- 22471169
TI  - Role of information technology (IT) in public health, India (problems &
      prospects): Role of information communication technology (ICT) in disease
      surveillance under Integrated Disease Surveillance Project (IDSP).
AB  - Information Communication Technology (ICT) has proven to be a strong public
      health tool. Keeping the future need of country and building National Disease
      Surveillance System, Integrated Disease Surveillance Project (IDSP) was launched
      by Hon'ble Union Minister of Health & Family Welfare in November 2004. It is a
      decentralized, State based surveillance program in the country. It is intended to
      detect early warning signals of impending outbreaks and help initiate an
      effective response in a timely manner. One of the major components of the project
      is the - use of Information Technology for collection, collation, compilation,
      analysis and dissemination of data besides distance education and video
      conferencing. A network of 800 sites across India has been established through
      Satellite, Broadband and High end Video conferencing equipments. The network is
      managed by a team of data managers and data entry operators at all state
      surveillance units and district surveillance units respectively. The network was
      proven to be extremely useful to respond to the current influenza A H1N1
      pandemic. It is proposed to extend the network to cover private sector and
      provide convergence with other National Health Programs.

PMID- 22471170
TI  - Study of different methods of susceptibility testing of M. tuberculosis.
AB  - This communication is on a multi-centre collaborative study carried out by New
      Delhi Tuberculosis (NDTB) Centre, Delhi, to compare the different methods of drug
      susceptibility testing (DST) of Mycobacterium tuberculosis for Streptomycin,
      Rifampicin, Isoniazid and Ethambutol in various accredited laboratories 40
      samples (selected by simple random sampling technique) from sputum positive out
      patients presenting between December 2004 and January 2005 were collected at New
      Delhi Tuberculosis Centre from 24 males and 16 females (age ranging from 18 to 55
      years) were taken up for culture and susceptibility testing. The proportion
      method of DST done at NDTB Centre was taken as standard for comparing the other
      methods after it was found to have a good agreement with the proportion method
      performed at Tuberculosis Research Centre, Chennai (Kappa coefficient 0.75 to 1).
      All 40 sub-cultures were processed for DST by the resistance ratio and proportion
      methods at NDTB Centre. Also, the 40 sub-cultures were sent to Central JALMA
      Institute for Leprosy (JALMA), Agra that used the resistance ratio method and 25
      sub-cultures were transported to National Institute of Communicable Diseases
      (NICD), Delhi for performing the Bactec 460TB method. The resistance ratio and
      proportion methods were compared both intra-laboratory (NDTB Centre) and inter
      laboratory (NDTB Centre and JALMA). The sensitivity and specificity of the
      resistance ratio method compared to the proportion method both inter and intra
      laboratory, were very high for all the drugs (except Ethambutol inter
      laboratory). This was corroborated by the good agreement between the resistance
      ratio performed at the two centres. Bactec 460TB method, on the other hand, did
      not have acceptable measures of validity (sensitivity and specificity) compared
      to the proportion method for Streptomycin and Ethambutol. Both resistance ratio
      method & proportion method are comparable and either can be used for making
      clinical decisions. But Bactec 460 method, despite yielding early results loses
      out on validity.

PMID- 22471171
TI  - HIV knowledge, attitudes and practices among 12th-grade students in southern
      India, before and after an HIV-education session.
AB  - Education about sex and sexually transmitted disease is uncommon in southern
      India, and it is unclear whether classroom instruction in HIV can change student
      knowledge or attitudes. OBJECTIVES: To assess students' knowledge, attitudes, and
      practices about HIV before and after an educational session. 1,168 12th-grade
      students from four schools in the Tamil Nadu state of India participated in a one
      to two hour session on HIV. Students completed anonymous, Tamil-language
      questionnaires about HIV topics immediately before and after the session. Many
      students endorsed erroneous facts about HIV before the session, but correct
      survey scores increased by 24% afterwards. Thirty-five percent of students knew
      someone with HIV, and familiarity with an HIV-infected person was associated with
      greater pre-session HIV knowledge. HIV knowledge was equivalent in students who
      held stigmatizing and non-stigmatizing attitudes, but the session significantly
      reduced stigmatizing attitudes from 38% of students to 29%. One percent of
      students admitted to having had sex. The proportion of students who think
      classroom HIV education is important rose significantly from 80% before the
      session to 90% after. Indian 12th-graders lack some basic knowledge about HIV,
      but only a couple hours of education was necessary to significantly and
      substantially increase short-term knowledge. Education-but not factual knowledge
      per-se was associated with a decrease in stigmatizing attitudes. Because most
      12th-graders reported not having had sex, high school may be an appropriate age
      for intervention. Most students desired HIV education in the classroom, and
      exposure to this education increased its acceptance.

PMID- 22471172
TI  - Invasion of toxic marine cyanobacteria in to the tsunami affected coastal
      villages of southern India.
AB  - This documentation explores the facts about the invasion of marine cyanobacteria
      in to the tsunami affected coastal villages of Nagapattinam district of Tamilnadu
      and Karaikkal district of Pondicherry Union Territory (UT) in southern India.
      Water samples were collected from eight tsunami-hit coastal villages in different
      open water sources. The collected samples were processed for detecting marine
      cyanobacterial growth. Totally 110 water samples were processed, three samples
      were positive for the toxic cyanobacteria, Lyngbya sp., and nine for nontoxic
      species such as Epithemia sp.,, Johannesbaptistia pellucida, Oscillatoria
      princeps, Phormidium fragile, Synechocystis sp. Besides posing a public health
      risk because of the toxic cyanobacteria, the bloom formation by the
      cyanobacterial species such as Anabaena, Microcystis, Lyngbya, Plectonema,
      Phormidium contaminated the water bodies and deteriorated the water quality in
      the tsunami affected villages. The study revealed that another kind of public
      health risk from the invasion of toxic cyanobacteria to the costal ecosystem
      during the tsunami. It is necessary, in this context, that the surveillance
      mechanism, which is geared up during or after natural disasters, should have a
      provision to monitor the transportation of toxic elements/organisms from marine
      system to coastal/inland ecosystems and to control such organisms.

PMID- 22471173
TI  - A study of frequency distribution and some epidemiological features of reported
      cases and deaths of dengue in Ludhiana district during the year 2008.
AB  - There were 7337 cases and 50 deaths reported in the state of Punjab from 1997 to
      2008 of which Ludhiana district of Punjab contributed 4973 cases and 32 deaths.
      Number of cases (2506) and deaths (13) reported were highest in Ludhiana in the
      year 2008. City/Area wise reporting of dengue cases in hospitals of Ludhiana in
      2008 show that the disease is mostly prevalent in the urban areas but now has
      been reported from rural areas also as 2 cases have been reported from village
      Kumkalan, block Mangat, Ludhiana. Age wise distribution of the cases shows
      maximum incidence per lakh population in 31-50 years (52.06) followed by 16-30
      years (49.00) and lowest in infants (0.36). The difference of incidence in
      various age groups has been found highly significant. Out of the 2988 cases
      reported from Ludhiana district, there were 1993 males, 989 females and no
      mention of the sex in 6 cases. The difference of incidence in males and females
      has been found highly significant. Month wise distribution of the cases shows
      maximum incidence per lakh population to be the highest in October (90.27)
      followed by November (33.39) and December (23.18). The difference of incidence in
      various months has been found highly significant. As the dengue is increasingly
      becoming an escalating problem it needs necessary control measures especially
      regarding BCC activities and appointment of Biologists at the district level in
      Punjab needs to be done.

PMID- 22471174
TI  - Level of knowledge regarding hepatitis-B immunization amongst health personnel in
      Delhi, India.
AB  - Hepatitis B infection is endemic throughout the world. Government of India
      started Hepatitis B immunization project for children less than one year of age
      in 15 cities and 32 selected districts in the country in the year 2002. This
      study was carried out to ascertain the level of knowledge regarding Hepatitis B
      immunization amongst primary care provider working in urban government
      dispensaries. Out of 12 municipal zones in Delhi [India], one was selected
      randomly i.e. South Municipal zone and all the 32 government dispensaries
      operational in this zone were covered. The study subjects were medical officer
      and health worker female. A single investigator carried out the survey during the
      period Oct-Dec' 05 using interview schedule bearing 15-item question based on WHO
      & GOI guidelines & broadly divided into three sub-groups and analysis carried
      through software statistical package [SPSS ver. 7]. Out of 172, a total of 141
      [82%] primary care provider i.e. 73 medical officers and 68 health worker female
      were contacted. The overall mean score amongst medical officer for Hepatitis B
      infection, Hepatitis B immunization & Cold chain component for Hepatitis B
      vaccine was found to be 89.33 [SD 1.21], 87.25 [SD 1.56] and 40.80 [SD 3.07].
      Similarly for health worker female, mean score was found to be 59.75 [SD 2.08],
      97.37 [SD 0.85] & 70.0 [SD 2.77] respectively. A clear difference was found
      between theoretical and practical knowledge aspect on the subject area with cold
      chain being identified as a weak link. It needs to be emphasized that Hepatitis B
      is "freeze-sensitive" vaccine and should be strictly preserved between 2-8
      degrees C temperatures as freezing has a detrimental effect on its potency.

PMID- 22471175
TI  - Evaluation of Diagnos Malaria Stix test (antigen detection assay) for diagnosis
      of malaria.
AB  - Malaria is one of the most common parasitic infection in India. The diagnosis
      largely depends on peripheral blood smear examination. Newer diagnostic methods
      like various antigen detection assays are now in use for prompt diagnosis and
      treatment. This study was done to determine the effectiveness of Diagnos Malaria
      Stix (antigen detection) assay in diagnosis of malaria. This involves detection
      of PfHRP-2 antigen and P.V. specific pLDH antigen. 162 patients with signs and
      symptoms of malaria included in the study. Leishman stained blood smear
      examination was done for all patients. Commercially available Diagnos Malaria
      Stix assay was used. Diagnos Malaria Stix showed sensitivity, specificity
      positive and negative predictive values of 100% each while Sensitivity,
      specificity, positive and negative predictive values of Leishman stained blood
      smear examination were 45.45%, 100%, 100% and 92% respectively.

PMID- 22471176
TI  - Prevalence of Ascogregarina spp. in the container breeding Aedes albopictus from
      Chikungunya fever affected areas of Kerala State, India.
AB  - The prevalence of protozoan, Ascogregarina sp. had been determined in the
      container breeding mosquitoes, Aedes albopictus. Since, the cyst of Ascogregarina
      might play role in the maintenance of the Chik virus during silent period, the
      presence of Ascogregarina has gained importance in recent days. The prevalence
      was found to be 71.62.

PMID- 22471177
TI  - Adherence to universal work precautions: a study among nurses and laboratory
      technicians in a teaching hospital of north India.

PMID- 22471178
TI  - An outbreak of cholera in and around Aurangabad.

PMID- 22471179
TI  - Utility of bone marrow culture in the definitive diagnosis of human brucellosis.

PMID- 22471180
TI  - Identification, characterization and antibiotic susceptibility pattern of non
      fermenters from clinical specimens in Lucknow, Uttar Pradesh.
AB  - Present study was an attempt to study the prevalence of nonfermenter and its
      antibiotic susceptibility pattern at CSM Medical University, Lucknow. All the
      isolates and samples were selected from clinical specimens received in
      Bacteriology section, P.G. Depart of Microbiology, for culture. The observation
      were made on the nonfermenter isolates that can be isolated from clinical
      specimen using simple Laboratory media e.g. Blood Agar & Mac Conkey agar. All
      relevant history & information were recorded from the subjects. A total of 8340
      specimen were screened for a period of one year. The prevalence of nonfermenters
      came to be 19.09% among all isolates. Most of spp. belongs to oxidase+ve group
      (77%). P. aeruginosa was found to be most common isolate (53%). Overall
      sensitivity profile for ciprofloxacin was 60%, P/T 58% & Amikacin 56%.
      Sensitivity of imepenem was 60% for multi-resistant isolates. The most resistant
      isolate was Sachrolytic Acinetobacter spp. The knowledge of synergism between
      drugs in context to different isolates may aid in effective therapy for these
      isolates.

PMID- 22471181
TI  - A coverage evaluation survey of JE vaccination in two districts of Karnataka.
AB  - A coverage evaluation survey was conducted in Mandya and Koppal districts of
      Karnataka state following the Japanese Encephalitis (JE) vaccination campaign.
      The purposes of the survey were to assess coverage of children in target age
      group by JE vaccination and to assess adverse events following immunisation
      against JE, the knowledge of health care providers and community about JE & mass
      vaccination for JE. The study design consisted of both quantitative and
      qualitative methods. The quantitative data was used to know the coverage levels
      for children. The qualitative data collected through interviews of head of the
      family in the sample households, selected health care workers using a structured
      pretested questionnaire. The standard cluster sampling method was used for
      selecting the sample of children to be evaluated. In Mandya district the
      evaluation showed 92% coverage in the selected sample of 313 children against the
      reported 83.85%. In Koppal district the evaluation showed 70% coverage, among the
      selected sample of 251 children, against the reported coverage of 69.8%. The
      incidence of adverse events was 4% in Mandya sample and 6.37% in Koppal sample.
      In Mandya district, about 42% of households had knowledge of JE. About 68% of
      households had prior knowledge of the immunization day. In Koppal district, the
      survey has revealed that only 19.85% of the heads of household had the knowledge
      of JE and 48.53% had the knowledge of JE vaccination before the day of
      vaccination campaign.

PMID- 22471182
TI  - Factors influencing blood donations and the rational use of blood.
AB  - A multicentric quasi-experimental study was conducted in Delhi, from March 2007
      to September 2007, on i) the factors which stimulate the donors to donate blood,
      ii) major barriers and myths associated with blood donation and iii) clinicians
      perception of the rational use of blood. The study design included a face-to-face
      survey, with a pre-tested questionnaire paper in two leading blood banks of Delhi
      and by relevant interviewers from the community and medical fraternity. The
      sample size was 240-blood donors from two different blood banks and the control
      group included 100 potential donors from community and 50 clinicians from various
      hospitals. The data generated was analyzed using excel sheet and Epi-Info
      software. The study revealed the factors which influence the blood donation
      included replacement credit and family/peer pressure. Regarding myths and
      barriers, among potential donors, about a quarter of them felt that it is time
      consuming, and 20% felt it could lead to sexual impairment or is not rewarding. A
      total of 10% were not aware about the blood donation while 15% said that donation
      time was inconvenient. Of the 50 clinicians, a quarter of them were not aware of
      the rational use of blood.

PMID- 22471183
TI  - Assessment of X-ray readers in TB prevalence surveys.
AB  - A prevalence study was carried out a rural community in Tiruvallur district in
      Tami Nadu to standardize the method of assessing an X-ray reader in tuberculosis
      (TB) prevalence surveys by means of different measures of agreement between the
      reader and a Standard Reader (SR). The exercise on assessing the X-ray readers
      was carried out on two occasions; one involving three trainee readers (R1, R2,
      and R3), and the other involving one trainee reader (R4). The extent of agreement
      was estimated using Kappa statistics (K), over-diagnosis, under-diagnosis, crude
      agreement and prevalence adjusted bias adjusted kappa (PABAK). The overall
      performance of readers R1, R2, and R3 was not satisfactory in terms of K (21, 34
      and 14%) in the first assessment. The K, over-diagnosis and under-diagnosis were
      estimated to be 61, 28 and 4% for R1, 63, 18 and 4% for R2 and 58, 31 and 5% for
      R3 in the final assessment. This suggested that R2 performed well compared to the
      other two readers. The K was 68% for R4 in the first assessment. As the over
      diagnosis was to the extent of 40%, the trainee reader underwent one more
      assessment. The K was 64% which was as good as before, but there was no
      improvement in the over-diagnosis (43.5%) in the second assessment. Based on the
      performance, only one reader (R2) was certified as qualified for X-ray reading in
      the first occasion while the reader (R4) assessed in the second occasion was not
      qualified. These findings were subject to the inherent variation in the SR's
      readings against which the readers were assessed.

PMID- 22471184
TI  - Laboratory selection of carbofuran tolerant line of Culex quinquefasciatus Say,
      the filarial vector at Mysore.
AB  - Carbofuran is a systemic insecticide/nematicide extensively employed in modern
      agriculture and public health to combat various insect pests and vectors. The
      development of insecticide resistance due to natural selection pressure by
      Anopheline and Culicine mosquitoes has created serious repercussions in mosquito
      control and disease eradication campaigns. In this regard Culex quinquefasciatus,
      a widely dispersed domestic mosquito and the only vector of lymphatic filariasis
      in India, was selected for the present experiment. In order to assess the
      resistance development in this species, it was subjected to carbofuran bioassay
      by employing WHO method for 10 generations. The results of larval selection test
      up to F10 revealed a significant increase in tolerance development in every
      generation compared to the susceptible F1. The results revealed up to 16.225
      times tolerance after 10 generations. The LC50 observed in F10 is 1.298 ppm
      compared to 0.08 ppm in the F1. The implications of the observations will be
      discussed.

PMID- 22471185
TI  - Serological study of rickettsial diseases in human and rodent population in
      Chittoor dist. (A.P.).
AB  - In India the presence of Rickettsial disease in human is documented in many
      states however, the data on presence of Rickettsial infection in Andhra Pradesh
      is very scare. Therefore, a study was undertaken in Chittoor district (A.P.) to
      see the prevalence of Rickettsial infection in human and rodent population. 3-5
      ml of human blood samples were collected from the patients attending the nearest
      hospitals of Tirumala, Tirupathi, Palmner and Chittoor areas. Live rodents were
      trapped and blood samples were collected from them during January and February
      2008. Sera was separated and tested by Weil Felix test. Two hundred human sera
      samples were tested. Of these 39 samples were found reactive with Weil Felix
      antigen. Of the 39 reactive, 31 were male and 8 female. All the human samples
      were showing reactivity at 1:20 dilution. Out of the 343 rodents samples tested,
      only 24 samples were showing reactivity. These were reactive at 1:20, 1:40 and
      1:80 dilutions with different types of Weil Felix antigens. Eight rodent sera
      samples were having titer 1:80 with Proteus OXK which is suggestive of presence
      of Scrub typhus in this region.

PMID- 22471186
TI  - Pattern and burden of animal bite cases in a tertiary care hospital in Haryana.
AB  - Rabies is an endemic disease in both developed and developing world and is
      responsible for a large number of morbidities and mortalities in humans. Limited
      supply of vaccine hampers the accessibility of life saving treatment. In our
      study carried out in a tertiary care hospital in Haryana showed that there were
      3617 animal bite cases reported in a year with an average of 9.91 new cases per
      day. The average economic burden related to management of these bite cases is 3.5
      lacs per month. This cost along with vaccine demand can be substantially reduced
      if intradermal schedule is introduced.

PMID- 22471187
TI  - Knowledge of swine flu among nursing staff of RIMS, Adilabad (AP).

PMID- 22471188
TI  - Snails as bio-indicators for dreaded trematodiasis diseases.

PMID- 22471189
TI  - Rapidly emerging novel metallo beta lactamase--New Delhi metallo beta lactamase-1
      (NDM-1)--is it a misnomer.

PMID- 22471190
TI  - Strongyloides stercoralis infection in an HIV positive patient--a case report
      from RIMS, Imphal, Manipur.
AB  - Strongyloides stercoralis, a nematode parasite in human with free living and
      autoinfective cycles, is often an asymptomatic infection of the upper small
      intestine. If the host becomes immunocompromised, autoinfection may increase the
      intestinal worm burden and lead to disseminated strongyloidiasis. We report a
      case of a 33 year old male HIV positive patient admitted on 2/6/08 in male
      medical ward, Regional Institute of Medical Sciences, Imphal, Manipur with
      complaints of loose stools, pain abdomen, nausea, vomiting, generalized weakness,
      loss of appetite and loss of weight for past one month with fever off and on.
      Stool examination reveals larvae of Strongyloides stercoralis. The patient was
      successfully treated with Ivermectin 200 microgm/kg daily for 2 days.

PMID- 22471191
TI  - Indian public health service: a need of the hour.

PMID- 22471192
TI  - High initial bacillary load in patients with pulmonary tuberculosis: an indicator
      of drug resistant tuberculosis.
AB  - This study conducted to evaluate the role of pretreatment bacillary load in
      predicting multi drug resistance tuberculosis (MDR-TB). Sputum smear positive
      cases of all pulmonary tuberculosis, who received standard short course
      chemotherapy under direct observation, were studied with pretreatment absolute
      acid fast bacilli (AFB) counts per 100 oil immersion fields and culture
      sensitivity assay for Mycobacterium tuberculosis. Pretreatment count of > or =
      850 bacilli per oil immersion field in category II cases and > or = 1200 bacilli
      per oil immersion field in category I cases was found to be a predictor of MDR-TB
      with sensitivity and specificity of 88.89% and 87.04% in category II; and 100%
      and 84.13% in category I subjects respectively. In conclusion, high bacillary
      count (3+) can be taken as a marker of MDR-TB, specially in treated cases of
      tuberculosis and requiring further investigation as well management of these
      cases on lines of multi drug resistance tuberculosis.

PMID- 22471193
TI  - Prevalence of community acquired MRSA in a tertiary care facility.
AB  - Traditionally, methicillin resistant Staphylococcus aureus (MRSA) is considered
      as a nosocomial pathogen, but an increasing prevalence of community acquired MRSA
      is being reported worldwide including India, which implies a strategic change in
      the antibiotic of choice for treatment of community acquired Staphylococcal
      infections, which till now is cloxacillin. This study is aimed at identifying the
      prevalence and susceptibility characteristics of community acquired MRSA in our
      hospital. The study group consisted of 208 consecutive MRSA identified on the
      basis of their resistance to cefoxitin disk (30 microg) by the disc diffusion
      method and mecA gene detection by polymerase chain reaction (PCR). Isolates were
      categorized as community acquired MRSA based on criteria for inclusion and their
      antibiotic susceptibility was compared with that of the hospital acquired MRSA
      isolates. Among the 208 MRSA analyzed, 18% (n = 37) were community acquired and
      were from infections such as cellulitis and superficial injuries. The isolates
      were significantly more sensitive to ciprofloxacin than the hospital acquired
      MRSA isolates. The prevalence of community acquired MRSA in this study (18%) is
      comparable to its prevalence in other studies across India. Susceptibility to
      antibiotics other than glycopeptides was an important characteristic of community
      acquired MRSA. In the absence of other reliable phenotypic test for its
      identification, susceptibility to ciprofloxacin is suggested as an alternative. A
      prudent clinician should be aware that, cloxacillin, the drug of choice for skin
      infections such as carbuncle and cellulitis, will not be effective in these cases
      and that community acquired MRSA has a range of antibiotics to choose from, other
      than the glycopeptides, when compared with that of hospital acquired MRSA.

PMID- 22471194
TI  - Unusual manifestations in dengue outbreak 2009, Delhi, India.
AB  - Epidemics of Dengue fever (DF) and Dengue hemorrhagic fever (DHF) are common in
      Southeast Asia. DF is defined & classified according to WHO criteria. Variable
      clinical manifestations of DF & DHF have been described in earlier studies. But
      some patients present with unusual clinical features and clinical profile not
      classifiable according to the present WHO criteria. Some of these complications
      if not recognized early and treated properly can even prove fatal. So this study
      was done to describe various clinical features in Dengue fever with special
      emphasis on unusual manifestations. This study was conducted at University
      College of Medical Sciences and associated Guru Teg Bahadur hospital; a tertiary
      care hospital, located in East Delhi in India. It was a retrospective study of 76
      patients of probable DF; including 4 cases of DHF (according to WHO
      classification); 60 males & 16 females above 12 years of age admitted in medical
      wards of Guru Teg Bahadur hospital in an outbreak of DF which occurred during
      September-December 2009. The data obtained was analyzed to see clinical and
      laboratory profile of DF/DHF with special emphasis on unusual manifestations. The
      mean age of the patients was 28 +/- 9.6 years. Fever was present in all the cases
      with an average duration of fever being 5.47 +/- 2.2 days with body ache,
      (84.2%), vomiting (61.8%), abdominal pain (51.3%) and headache (19.7%) being the
      other presenting complaints. Hemorrhagic manifestations in the form of gum
      bleeding and epistaxis (35.5%), positive tourniquet test (27.6%); skin rashes
      (15.8%), melena (15.8%) and hematemesis (5.26%) were also present. In our study a
      fair no of patients presented with unusual symptoms like pain in abdomen 39
      (51.3%), nausea 32 (42.1%), & vomiting 47 (61.8%), which is higher than that
      reported previous outbreak. Of the 39 patients who presented with abdominal pain;
      ultrasonography of abdomen was done in 25 patients. Fifteen (38%) of these were
      found to have acalculous cholecystitis. Amongst the known manifestations of DF,
      abdominal pain has been well described, but acalculous cholecystitis as a cause
      of abdominal pain is scantly reported. Another unusual manifestation was the
      presentation of patients (7.89%) in circulatory failure without the evidence of
      plasma leakage and not fulfilling all the criterion proposed by WHO for DHF/DSS.
      All of the above patients had very low platelet counts & tourniquet test was
      positive in all these six patients. Hepatomegaly and splenomegaly were observed
      in 34.2% and 7.89% of cases, respectively. Renal dysfunction was observed in
      13.1% of cases. Laboratory investigations revealed thrombocytopenia (with a
      platelet count of < 100,000/microl) in all cases. Leucopenia (WBC < 4,000/mm2)
      and Hemoconcentration (Hct > 20% of expected for age and sex) were found in 38%
      and 5.26% of the cases, respectively. Results of our study indicate that apart
      from usual manifestations, sometimes unusual but clinically extremely important
      manifestations can occur which if not detected early can prove fatal. So a
      vigilant and timely approach is warranted.

PMID- 22471195
TI  - "Inducible clindamycin resistance in Staphylococcus aureus isolated from clinical
      samples".
AB  - Increasing frequency of methicillin resistant Staphylococcus aureus (MRSA)
      infections and changing patterns in antimicrobial resistance have led to renewed
      interest in the use of macrolide-lincosamide-streptogramin (MLS) antibiotics to
      treat such infections. Inducible macrolides, lincosamides, type B streptogramins
      (MLS(Bi)) resistance has to be identified to avoid clinical failure of
      clindamycin therapy. Hence we wanted to study the incidence of inducible
      clindamycin resistance in MRSA and methicillin susceptible Staphylococcus aureus
      (MSSA). Staphylococcus aureus was isolated in 1049 patients over a period of two
      years from various clinical materials. All the isolates were tested for inducible
      clindamycin resistance by disc diffusion induction test (D-zone test). A total of
      726 MSSA and 323 MRSA were tested for the inducible clindamycin resistance
      (MLS(Bi)) by D-zone test. Inducible resistance to clindamycin (MLS(Bi)) where D
      test was positive was observed in 42.1% of MRSA and 3.4% of MSSA. Inducible
      resistance to clindamycin (MLS(Bi)) was found to be higher in MRSA than MSSA
      isolates. Clindamycin is one of the important alternative antibiotics to treat
      MRSA infections in resource poor countries. To avoid treatment failure with
      clindamycin, prior D testing is necessary.

PMID- 22471196
TI  - Ovipositional site selection and oviposition behaviour of spp. Forcipomyia
      (Diptera: Ceratopogonidae) from Uttar pradesh, India.
AB  - The biting midges, Forcipomyia is a vector of numerous disease of vertebrate.
      Forcipomyia is widly distributed in middle Gangetic Region of Uttar Pradesh.
      Ovipositional site selection is probably the single most important aspect of
      insect behaviour from an applied point of view. Vector selection behaviour is
      mainly influenced by the action of temperature. After Copulation, the female of
      Forcipomyia dibiyapurensis remain inactive for about 5-6 hrs and Forcipomyia
      barkhai become inactive for about 3 hrs. After that female become activated and
      goes for blood meal, which is helpful to development of batch of egg. Female
      activity starts for the oviposition at the commencement of down, both lay the
      eggs in humid soil around the water bodies.

PMID- 22471197
TI  - A study on dengue outbreak during 2009 in Bhopal and Indore districts of Madhya
      Pradesh, India.
AB  - An outbreak of mysterious virus disease reported from Bhopal, Indore and
      adjoining districts of Madhya Pradesh (MP) state during 2009. The outbreak
      started in Bhopal in early September and then from Indore in last week of
      September. Subsequently cases were also reported from adjoining districts. On
      basis of Epidemiological, Clinical, Entomological and Laboratory findings dengue
      outbreak was declared in the area. A total of 620 IgM Elisa positive cases were
      reported from Bhopal and Indore district and adjoining areas. The outbreak
      involved 8 districts in the state. The control measures were undertaken in the
      area and the outbreak of dengue subsided in December 2009.

PMID- 22471198
TI  - Intestinal parasites prevalence and related factors among school children in the
      rural area of central India.
AB  - A cross sectional study was conducted to determine the prevalence of intestinal
      parasitic infections and its epidemiological correlates among rural Indian school
      going children and to find out the effect of hygiene education on personal
      hygiene of school children at village Karanji (Kaji) in Wardha district of
      central India. Out of 172, 87 (50.6%) boys and 85 (49.4%) girls were examined.
      The mean age of the school children was 10.37 +/- 2.71. The prevalence of
      intestinal parasite infection was 7.56%. The prevalence was significantly high
      among barefoot children (OR = 8.99; 95% CI: 2.14 - 43.49) followed by those
      having poor hand washing practices (OR = 4.90; 95% CI: 1.30 - 20.01), not using
      sanitary latrine (OR = 2.49; 95% CI: 0.6 - 11.91)) and dirty untrimmed nails (OR
      = 1.98; 95% CI: 0.56 - 7.04). One month after hygiene education, there was
      significant improvement in the key personal hygiene behavior (p < 0.05). The
      proportion of children having practice of hand washing with soap after defecation
      significantly improved. Health education on personal hygiene to the school
      children was effective for behavior change. A multisectoral control approach and
      hygiene education will help health authorities in strategy of control programs
      for intestinal parasites among school going children.

PMID- 22471199
TI  - Gaps in the knowledge about advancements in rabies vaccines among the
      undergraduate medical students.
AB  - Enormous developments have taken place during the past few years in the field of
      Rabies prevention and control particularly rabies vaccines. Intra-dermal Rabies
      Vaccination (IDRV) has already emerged as a safe, ethical and cost-effective
      replacement. However appropriate dissemination of knowledge and implementation by
      medical fraternity is imperative for effective prevention and control of this
      fatal disease. Gaps were found in the knowledge of medical students regarding the
      newer rabies vaccines. This can be resolved to great extent by updating the
      undergraduate curriculum with the current control strategies used in this field.

PMID- 22471200
TI  - Impact of training workshop on knowledge, attitude and practices about HIV/AIDS
      among class IV employees at tertiary care teaching hospital, Loni in rural
      Maharashtra.

PMID- 22471201
TI  - Dengue hemorrhagic fever complicated with encephalopathy and mycocarditis.

PMID- 22471202
TI  - Benzene-induced histopathological changes and germ cell population dynamics in
      testes of Sprague Dawley rats.
AB  - Benzene has been considered as an occupational hematotoxin and leukemogen. The
      present study was conducted to determine the effects of oral administration of
      benzene on reproductive organs and testicular spermatogenesis in rats. Adult rats
      were divided into three weight matched groups (Gr. I-III) containing 6 each. Gr.
      I rats received vehicle only and served as control. Rats in Gr. II and III were
      fed orally with 0.5 and 1 ml kg(-1) dose of benzene for 14 and 9 days,
      respectively and autopsy was done on 15th and 10th day. Food and water intake and
      gross behavioral changes were recorded daily during the entire treatment. Results
      showed no significant change in reproductive organ weights viz. testis,
      epididymis and ventral prostate in benzene-treated (0.5 or 1 ml kg(-1)) rats than
      that in controls. But, caused a significant decrease (p < 0.005) in weights of
      seminal vesicles in rats treated with both 0.5 and 1 ml kg(-1) doses compared to
      control. In contrast, at higher dose (1 ml kg(-1)) of benzene, significant (p <
      0.001) decline in body weight and 100% mortality was observed on day 10 of
      autopsy. In treated rats, testicular cytotoxicity was marked by multinucleated
      giant cells formation, cytoplasmic vacuolization, pyknosis of nuclei,
      chromatolysis, desquamation and dissolution of germ cells in tubular lumen. The
      quantitative analysis of spermatogenesis showed a significant (p < 0.001)
      decrease in number ofA-spermatogonia (in 1 ml kg(-1) dose only), primary
      spermatocytes (non-pachytene and pachytene) and spermatids (round and elongated)
      in treated as compared to control rats. The diameters of testicular tubules and
      Leydig cells nuclei were also significantly (p < 0.001) reduced in treated rats.
      A steady loss in food and water intake recorded and signs of ill health were
      observed in treated (0.5 or 1 ml kg(-1)) rats. Results of the study indicated
      antitesticular lantispermatogenic effects of benzene at 0.5 and 1 ml kg(-1) dose
      in rats.

PMID- 22471203
TI  - Studies on influence of natural biowastes on cellulase production by Aspergillus
      niger.
AB  - The objective of this study was to determine the influence of natural biowaste
      substrates such as banana peel powder and coir powder at varying environmental
      parameters of pH (4-9) and temperature (20-50 degrees C) on the cellulase enzyme
      production by Aspergillus niger. The cellulase enzyme production was analyzed by
      measuring the amount of glucose liberated in IU ml(-1) by using the
      dinitrosalicylic acid assay method. The substrates were pretreated with 1% NaOH
      (alkaline treatment) and autoclaved. The maximum activity of the enzyme was
      assayed at varying pH with temperatures being constant and varying temperatures
      with pH being constant. The highest activity of the enzyme at varying pH was
      recorded at pH 6 for banana peel powder (0.068 +/- 0.002 IU ml) and coir powder
      (0.049 +/- 0.002 IU ml(-1)) and the maximum activity of the enzyme at varying
      temperature was recorded at 35 degrees C for both banana peel powder (0.072 +/-
      0.001 IU ml(-1)) and coir powder (0.046 +/- 0.003 IU ml(-1)). At varying
      temperatures and pH the high level of enzyme production was obtained at 35
      degrees C and pH 6 by using both the substrates, respectively. However among the
      two substrates used for the production of cellulases by Aspergillus niger banana
      peel powder showed maximum enzymatic activity than coir powder as substrate.

PMID- 22471204
TI  - Transferability of STS markers in studying genetic relationships of marvel grass
      (Dichanthium annulatum).
AB  - Transferability of sequence-tagged-sites (STS) markers was assessed for genetic
      relationships study among accessions of marvel grass (Dichanthium annulatum
      Forsk.). In total, 17 STS primers of Stylosanthes origin were tested for their
      reactivity with thirty accessions of Dichanthium annulatum. Of these, 14 (82.4%)
      reacted and a total 106 (84 polymorphic) bands were scored. The number of bands
      generated by individual primer pairs ranged from 4 to 11 with an average of 7.57
      bands, whereas polymorphic bands ranged from 4 to 9 with an average of 6.0 bands
      accounts to an average polymorphism of 80.1%. Polymorphic information content
      (PIC) ranged from 0.222 to 0.499 and marker index (MI) from 1.33 to 4.49.
      Utilizing Dice coefficient of genetic similarity dendrogram was generated through
      un-weighted pairgroup method with arithmetic mean (UPGMA) algorithm. Further,
      clustering through sequential agglomerative hierarchical and nested (SAHN) method
      resulted three main clusters constituted all accessions except IGBANG-D-2. Though
      there was intermixing of few accessions of one agro-climatic region to another,
      largely groupings of accessions were with their regions of collections. Bootstrap
      analysis at 1000 scale also showed large number of nodes (11 to 17) having strong
      clustering (> 50). Thus, results demonstrate the utility of STS markers of
      Stylosanthes in studying the genetic relationships among accessions of
      Dichanthium.

PMID- 22471205
TI  - Manganese induced changes in growth, chlorophyll content and antioxidants
      activity in seedlings of broad bean (Vicia faba L.).
AB  - The effect of manganese (Mn) on broad bean (Vicia faba L.) was studied with
      regard to growth, Mn accumulation in root and shoot, chlorophyll, proline content
      and peroxidase activity. Seeds were treated with Mn (10, 20, 40, 80,120,160
      microM) and grown hydroponically up to 15 days. Manganese level in both root and
      shoot increased progressively in response to increasing concentration and it was
      high in roots (13 fold) overthe shoots (8 fold). The reductions in root (52%) and
      shoot (62.92%) development were evident for the maximum Mn concentration (160
      microM). The chlorophyll amount gradually declined with increasing Mn
      concentrations and attained its maximum (42%) at 160 microM. By contrast, the
      guaiacol peroxidase activity was high (71%) along with the accompanying rise in
      proline content (75%) in shoots of the highest Mn concentration (160 microM).
      However, there was about 2 fold increase in total glutathione content at 40
      microM than the basal level and further declined to 21.65 microg g(-1) fresh wt.
      at 160 microM Mn. The alterations in overall reflected Mn concentration-dependent
      changes in the parameters studied. The results suggest thatthe plant Vicia faba
      L. copes with Mn exposure through enhanced production of antioxidants.

PMID- 22471206
TI  - Size exclusion chromatography for the removal of pigments from extracellular
      ligninolytic enzyme extracts from decayed wheat straw.
AB  - Solid-state fermentation of wheat straw was carried out by a native white rot
      basidiomycete Daedaleopsis flavida strain 5A. Extract prepared from the 12-day
      decayed wheat straw contained extracellular ligninolytic enzymes like manganese
      peroxidase (MnP), manganese-independent peroxidase (MIP), lignin peroxidase (LiP)
      and laccase along with straw-degraded products and pigments. Sephacryl S-200 size
      exclusion chromatography in 16/100 column was used for the separation of these
      ligninolytic enzymes and straw-degraded products and pigments. Recovery of
      pigment-free ligninolytic enzyme activities as protein was 40% of the total
      proteins loaded and specific LiP activity increased 34 fold after size exclusion
      chromatography. Thus accurate estimation of LiP by veratryl alcohol oxidation
      assay was possible only after the removal of interfering pigments. The
      reproducibility of size exclusion chromatography is adjudged satisfactory from
      the consistent results obtained after seven repetitive uses of matrices.

PMID- 22471207
TI  - Benthic polychaetes in the Ratnagiri bay, India: influence of anthropogenic
      factors.
AB  - Study of changes in macrobenthic community structure is an intrinsic part of many
      environmental monitoring programmes. Hence, it is pivotal to distinguish the
      effects of natural and anthropogenic factors on these sensitive organisms for
      accurate assessment and management of coastal environment. Polychaete species
      diversity of five stations in the Ratnagiri bay was investigated during
      premonsoon and postmonsoon months in 2007. Though no spatial trends in polychaete
      diversity vis-a-vis the pollution was visible, the polychaete univariate indices
      were uniformily better in premonsoon indicating clear seasonal trends. Shannon
      diversity values ranged from 1.4-2.4 during premonsoon and 0.6-1.6 during
      postmonsoon. Station 5, which was most impacted by anthropogenic wastes as
      demonstrated by the anoxic conditions coupled with higher nutrient load, had
      comparatively higher H' values (1.9 and 1.6) and better evenness values (0.9 and
      0.7) during both seasons indicating that the polychaetes were not influenced by
      anthropogenic contamination. The study indicates that the polychaete distribution
      and diversity in the bay were governed primarily by variations in sediment
      texture rather than the anthropogenic disturbances.

PMID- 22471208
TI  - Predictive distribution modeling for rare Himalayan medicinal plant Berberis
      aristata DC.
AB  - Predictive distribution modelling of Berberis aristata DC, a rare threatened
      plant with high medicinal values has been done with an aim to understand its
      potential distribution zones in Indian Himalayan region. Bioclimatic and
      topographic variables were used to develop the distribution model with the help
      of three different algorithms viz. Genetic Algorithm for Rule-set Production
      (GARP), Bioclim and Maximum entropy (MaxEnt). Maximum entropy has predicted wider
      potential distribution (10.36%) compared to GARP (4.63%) and Bioclim (2.44%).
      Validation confirms that these outputs are comparable to the present distribution
      pattern of the B. aristata. This exercise highlights that this species favours
      Western Himalaya. However, GARP and MaxEnt's prediction of Eastern Himalayan
      states (i. e. Arunachal Pradesh, Nagaland and Manipur) are also identified as
      potential occurrence places require further exploration.

PMID- 22471209
TI  - Cardioprotective effects of Commiphora mukul against isoprenaline-induced
      cardiotoxicity: a biochemical and histopathological evaluation.
AB  - Commiphora mukul commonly known as Guggul is one of the oldest and commonly
      consumed herb for promoting heart and vascular health. Present study was
      undertaken to evaluate cardioprotective potential of Commiphora mukul against
      isoprenaline-induced myocardial necrosis in rats. Wistar albino rats were divided
      into three main groups: sham (saline only), isoprenaline control (saline and
      isoprenaline) and Commiphora mukul treated (Commiphora mukul and isoprenaline)
      groups. Commiphora mukul was administered in three doses 100, 200 and 400 mg kg(
      1) p.o. for 30 days. On 29th and 30th day, the animals of isoprenaline control
      and Commiphora mukulpretreatment groups were administered isoprenaline (85 mg kg(
      1); s.c.), consecutively at an interval of 24 hr. Isoprenaline administration
      produced a significant (p < 0.05) decrease in myocardial antioxidants; superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), reduced
      glutathione (GSH), and myocyte injury marker enzymes creatine-phosphokinase-MB
      (CK-MB) and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation;
      malondialdehyde (MDA) in heart. Commiphora mukul pretreatment reversed the
      isoprenaline-induced oxidative changes in rat myocardium by significant (p <
      0.05) increase in SOD, CAT, GSHPx, GSH and reduction of MDA. In addition to
      improving myocardial antioxidant status, Commiphora mukul also prevented the
      leakage of LDH and CK-MB from heart. Further, histopathological examination
      showed the reduction of necrosis, edema and inflammation following Commiphora
      mukul pretreatment. Based on present findings, it is concluded that Commiphora
      mukul may be a potential preventive and therapeutic agent against the oxidative
      stress associated ischemic heart disease owing to antioxidant and
      antiperoxidative activity.

PMID- 22471210
TI  - Influence of lignin, pentachlorophenol and heavy metal on antibiotic resistance
      of pathogenic bacteria isolated from pulp paper mill effluent contaminated river
      water.
AB  - Pulp paper mill pollutants are the major source of aquatic contamination having
      metals, lignin and chlorophenols. Study was conducted to see the effect of these
      contaminants on antibiotic resistance pattern of isolated bacteria. Pulp paper
      effluents were evaluated for its physico-chemical properties i.e, BOD 72143 +/-
      164.81 to 22.32 +/- 2.48, COD 213136 +/- 583.59 to 60.40 +/- 6.34, total phenol
      386 +/- 71.24 to 0.43 +/- 0.0, lignin 26312 +/- 258.59 to 73.67 +/- 31.81and
      microbial quality i.e. K. pneumonae, S. typhi, S. faecalis, P. aeruginosa, E.
      coli, Ent. faecalis, A. hydrophila, B. subtilis, S. aureus, Y enterolitica and V
      vulrificus. Antibiotic sensitivity (10-30 microg), heavy metal resistance (100
      1000 microg ml(-1)), lignin (1000-10,000 ppm) and pentachlorophenol (100-1000
      ppm) tolerance of bacterial strains were assessed by seven classes of
      antibiotics. Eleven bacterial isolates were found multidrug resistant towards
      antibiotics, heavy metal, lignin and PCP. Out of 11 isolates, 90.9% were found
      resistant against eleven antibiotics which acquired 100% resistant in presence of
      heavy metal, lignin and chlorophenols. Results also revealed that concentration
      of lignin (50-350 ppm) and PCP (5-30 ppm) induced maximum growth (273-8050 cfu
      ml(-1)) of pathogenic bacteria in river water.

PMID- 22471211
TI  - Zinc and copper induced changes in physiological characteristics of Vigna mungo
      (L.).
AB  - The effect of deleterious concentration of zinc and copper provided either
      individually or in combination in the nutrient media was investigated in order to
      assess the effect of metal interaction in Vigna mungo (L.). Both metals showed
      negative effect and led to a marked decrease in seed germination (20%), seedling
      growth (91.7%) and nitrate reductase activity (85.7%) with the increase in metal
      concentrations. The present study also emphasizes on the response of catalase and
      peroxidase enzyme under zinc and copper stress. Both antioxidant enzymes
      exhibited an increasing trend under different treatment conditions but it was
      reverse at highly toxic metal concentration. The results showed active
      involvement of peroxidase enzyme in regulating oxidative stress rather than
      catalase enzyme, as the specific activity of peroxidase enzyme got increased by
      8.94% under the combined metals stress whereas catalase activity got declined by
      60.97% in comparison to control due to excessive stress. The combined effect of
      copper and zinc metal was more pronounced in comparison to their individual
      effects.

PMID- 22471212
TI  - Salt stress induced alteration in growth characteristics of a grass Pennisetum
      alopecuroides.
AB  - Salinity is one of the major abiotic stresses that adversely affect crop
      productivity and quality. The present investigation was carried out to study the
      alterations in the growth characteristics of a grass species, Pennisetum
      alopecuroides under the influence of sodium chloride (NaCl) salinity. From the
      results it is clear that shoot length of Pennisetum alopecuroides was increased
      by 13.17% at 100 mM NaCl concentration while the root length was observed to be
      increased at 50 mM NaCI concentration by 26.93%.Maximum height of the plant was
      observed by 18.23% at 50 mM while shoot to root ratio was higher at 300 mM
      concentrations by 29.17% increase over the control. Moreover, the maximum percent
      increase in leaf area was recorded as 11.17% (100 mM). Fresh weight was increased
      by 50.92% at 100 mM while dry weight of the experimental grass was increased by
      33.64% at the same concentration of salt to the rooting medium while moisture
      percentage was increased to a maximum by 24.61% at 50 mM. It appears that the
      grass species studied exhibit a moderate salinity tolerance as far as linear
      growth of plant is concerned.

PMID- 22471213
TI  - In-situ monitoring of chromium cytotoxicity in sugarcane.
AB  - The potential of in-situ monitoring of cytotoxic effects of chromium through root
      tip assay was studied in a sugarcane cultivar CoLk 8102 (Saccharum spp. hybrid).
      Sugarcane setts supplied with graded concentrations of chromium (VI), exhibited a
      reduction of 85.92 and 95.10 % in mean root length at 40 and 80 ppm Cr dosages
      along with 61.25 and 82.50% reduction in mean root number/node respectively.
      Mitotic index of root tip cells of treated setts declined and the frequency of
      aberrant mitotic phases increased pari passu to the increasing chromium
      concentration. To compare and quantify the effect of graded chromium dosages on
      frequency of chromosome aberrations vis-a-vis inhibition of mitotic activity, a
      'Decretion factor' (D.F.) has been used for the first time. The value of DF
      increased with the increase in the chromium dosages. The increase in chromosome
      aberration frequency was low at low chromium dosages (1 or 2 ppm), but the high
      Cr dosages (40 and 80 ppm), induced sharp reduction in mitotic efficiency of root
      system along with anomalies in the process of cell division and induced
      chromosome aberrations in sugarcane root meristem, which in turn affected the
      over all plant growth.

PMID- 22471214
TI  - Characterization and optimization of conditions for biodegradation of sella-rice
      mill effluent.
AB  - The sella-rice mill effluent is a major environmental pollutant requiring proper
      treatment before disposal. The present study has been conducted to isolate and
      characterize micro-organisms capable of growing on sella-rice effluent and to
      optimize conditions for its rapid bioremediation. Using three different types of
      media (LB, YEPDA and PDA), a total of 139 isolates were isolated from effluent
      samples collected from three different locations. Out of these, 45 isolates were
      found to utilize starch on starch medium, eight isolates showing high efficiency.
      For the optimization of conditions for maximum utilization of starch by selected
      isolates, parameters such as effect of addition of carbon and nitrogen sources,
      effect of growth factors, temperature and pH were studied. Maximum growth
      (absorbance of 2.10) and starch-utilization (varying in the range of 2.33 to
      3.62) was observed on starch medium supplemented with peptone and yeast extract
      at 30 degrees C with a pH of 6.0. These bacterial isolates also reduced the
      amount of starch (80.10%), BOD (64.24%) and COD (75.0%) of sella-rice mill
      effluent after 15 days of incubation. On the basis of morphological and
      biochemical characteristics, the selected isolates were found to belong to the
      genera Lactobacillus and Micrococcus.

PMID- 22471215
TI  - Characterization of two metal resistant Bacillus strains isolated from slag
      disposal site at Burnpur, India.
AB  - Two strains of Bacillus sp. resistant to arsenate and lead designated as AsSP9
      and PbSP6, respectively were isolated from the slag disposal site. They were
      identified to be related to Bacillus cereus cluster on the basis of 16S rDNA
      based sequence analysis and phenotypic characteristics. Both were rod-shaped
      (AsSP9, 2-5 microm and PbSP6, 2-4 microm), aerobic, salt tolerant (2-8% NaCI),
      endospore forming bacteria with minor differences like the AsSP9 showed
      sporangial bulging and PbSP6 had positive lipase activity. The temperature range
      for their growth was 20-40 degrees C and pH range 6.0-9.0 with an optimum
      temperature of 37 degrees C and pH of 7 for both strains. The principal nitrogen
      sources forAsSP9 and PbSP6 were DL-Tryptophan and L-Phenylalanine, respectively.
      The suitable carbon source forAsSP9 was lactose and for PbSP6 sucrose. The heavy
      metal accumulation efficiency was found to be 0.0047 mg g(-1) of dry mass
      forAsSP9 and 0.686 mg g(-1) of dry mass for PbSP6.

PMID- 22471216
TI  - Characterization of protease from Alcaligens faecalis and its antibacterial
      activity on fish pathogens.
AB  - Alcaligens faecalis AU01 isolated from seafood industry effluent produced an
      alkaline protease. The optimum culture conditions for growth as well as enzyme
      production were 37 degrees C and pH 8. The partially purified protease had
      specific activity of 9.66 with 17.77% recovery with the molecular weight of 33
      kDa and it was active between 30-70 degrees C and optimum being at 55 degrees C
      and pH 9. The enzyme retains more than 85% activity at 70 degrees C and 78% even
      at pH 10. The enzyme inhibited the growth of fish pathogens such as
      Flavobacterium sp., Pseudomonas fluorescens, Vibrio harveyi, Proteus sp. and
      Vibrio parahaemolyticus. From the present study it can be concluded that
      Alcaligens faecalis AU01 has the potential for aquaculture as probiotic agent and
      other several applications.

PMID- 22471217
TI  - Live algae as a vector candidate for hydrophobic polychlorinated biphenyls
      translocation to bivalve filter feeders for laboratory toxicity test.
AB  - Live algae carrying hydrophobic xenobiotics can be an effective vector candidate
      for the chemical translocation to filter feeders in the laboratory toxicity test,
      but information on their application is lacking. Time-course uptake and
      elimination of polychlorinated biphenyls (PCBs) (0, 50, 100, and 500 ng g(-1) by
      two key algal foods, Isochrysis galbana and Tetraselmis suecica, were measured.
      Both of the algae achieved maximum concentration in an hourafter PCBs exposure
      regardless the chemical concentrations in our time-course measurements (0, 1, 5,
      10, 24, 48 and 72 hrs). Once achieved the maximum concentration, the algae
      shortly exhibited elimination or eliminating tendency depending on the chemical
      concentrations. Algae exposed to the chemical for 1 and 24 hrs (hereafter 1 and
      24 hr vectors, respectively) were then evaluated as a chemical translocation
      vector by feeding test to larval and spat Crassostrea gigas. In the feeding test
      the 24 hr vector, which contained lower chemicals than the 1-hr vector, appeared
      to be more damaging the early lives of the oyster. This was particularly
      significant for vectors of higher PCBs (p<0.05), probably due to algal reduction
      in food value by the prolonged chemical stress. These findings imply that 1 hr
      exposure is long enough for a generation of algal vector for laboratory toxicity
      test, minimizing data error resulted from reduction in food value by longer
      chemical stress.

PMID- 22471218
TI  - Effects of granulated baits on meso and macrofauna in soybean soil system.
AB  - Studies were done to see the effects of five toxic baits based on metaldehyde
      and/or carbaryl on the taxonomic composition of soil meso and macrofauna, and
      determined the density of beneficial organisms in soybean under no tillage. Six
      treatments were tested and soil monoliths were taken before application and at 45
      and 75 days after application (DAA). Before application, 1601 individuals were
      recorded, belonging 1086 to mesofauna and 515 to macrofauna. In soil mesofauna
      such as Annelida: Enchytraeidae (44%), Nematoda (33%) and Arthropoda (23%) were
      found. In the macrofauna Arthropoda 93% and Annelida: Oligochaeta, Megadrilli 7%
      were observed. No differences were observed among the treatments (p>0.05) in the
      total mesofauna density, at 45 and 75 DAA. The density of enchytraeids, mites,
      collembolans and symphylids showed no differences at45 and 75 DAA (p > 0.05). The
      total macrofauna density showed differences (p < 0.05) at 45 and 75 DAA. The
      highest density was obtained with 4 kg ha(-1) MataBibos Acay at 45 and 75 DAA.
      Earthworm and diplopod densities at45 and 75 DAA showed no differences (p>0.05).
      The diversity of meso and macrofauna was not affected at 45 and 75 DAA. Bait
      application did not affect either the abundance or the diversity of soil
      beneficial invertebrates.

PMID- 22471219
TI  - The behaviour of Ailanthus altissima weed and its effects on natural ecosystems.
AB  - Ailanthus altissima is an invasive species for the native flora of Greece and it
      could pose a serious threat to the biodiversity and the functioning of
      ecosystems. The purpose of this study was to investigate the spreading of
      Ailanthus altissima in urban and non urban areas of North and Central Greece and
      also to evaluate the effects of its spreading on species composition and
      floristic diversity in natural ecosystems. The spreading of Ailanthus altissima
      in urban areas is very intense, mainly in abandoned places (35.29%). It is
      commonly found in non urban areas of Greece, especially in hedgerows of arable
      lands (36%) and adjacent wetlands (17%). It is less common in forests (4%),
      shrublands (11%) and grasslands (9%). The spread of Ailanthus altissima in urban
      and natural ecosystems is relatively recent. Although it has been recorded at
      altitudes of up to 640 m, it usually appears at low altitudes of up to 200 m.
      Floristic diversity was found to be higher in the stands that it dominated (H' =
      1.574, H' = 1.890) in comparison to stands that were dominated by
      Quercuspubescens (H' = 1.468) or Q. coccifera (H' = 1.716). This may be
      contributed to the fact that in those stands synanthropic species, which are
      usually found in regions of intense human activity, were present together with
      typical forest vegetation species.

PMID- 22471220
TI  - Alterations of biochemical parameters in malformed Indian rice frogs, Rana
      limnocharis from Southern Taiwan.
AB  - The purpose of this study is to investigate the factors that cause malformed
      frogs in upstream Kaoping river (KP site) and Tungkang river (T site) of Southern
      Taiwan. In this experiment, the activities of monooxygenase (MO), glutathione-S
      transferase (GST), acetylcholinesterase (AchE) as well as the concentration of
      vitellogenin (Vg) in the liver were measured. Results show that activities of MO,
      GST and AchE, and Vg levels in normal frogs (male/female) were 0.09 +/-
      0.02/0.09+/-0.01 deltaA min(-1) mg(-1) protein, 0.12 +/- 0.04/0.13 +/- 0.04
      deltaA min(-1) mg(-1) protein, 6.13 +/- 2.69/6.01 +/- 2.09 U mg(-1) protein and
      0.87 +/- 0.42/2.18 +/- 0.50 microg mg(-1) protein, respectively. Activities of
      MO, GST and AchE, and Vg levels in malformed frogs (male/female) were 0.15 +/-
      0.04/0.21 +/- 0.07 deltaA min(-1) mg(-1) protein, 0.27 +/- 0.08/0.30 +/- 0.12
      deltaA min(-1) mg(-1) protein, 4.59 +/- 2.71/5.19 +/- 3.74 U mg(-1) protein and
      1.46 +/- 0.61/3.15 +/- 0.88 microg mg(-1) protein, respectively in KP site, and
      were 0.16 +/- 0.69/0.1 +/- 80.07 deltaA min(-1) mg(-1) protein, 0.21 +/-
      0.07/0.24 +/- 0.08 deltaA min(-1) mg(-1) protein, 5.13 +/- 4.58/3.94 +/- 1.33 U
      mg(-1) protein and 2.23 +/- 1.47/4.11 +/- 1.63 microg mg(-1) protein,
      respectively in T site. These results indicate that male and female malformed
      frogs in both rivers upstream are found with higher activities. No significant
      difference in AchE activity was found between normal and malformed frogs in this
      investigation. It is therefore reasonable to speculate that the organic chemicals
      released from agricultural activities are presumable the main factors that lead
      to the malformation of frogs.

PMID- 22471221
TI  - Risk assessment of heavy metal contamination in soil and wild Libyan jird
      Meriones libycus in Riyadh, Saudi Arabia.
AB  - This study was undertaken to document the impact of heavy metal pollution on the
      Libyan jird, Meriones libycus and to contribute to an environmental impact
      statement for the rapidly growing City of Riyadh. All metal concentrations in
      surface soil of a polluted site (within Riyadh City) were higherthan those from a
      reference site (outside the city).Although Pb declined versus earlier reports on
      Riyadh soil, Cd (0.97 microg g(-1)) and Hg (0.28 microg g(-1)) were above some of
      the most stringent quality guidelines (0.07-0.62 microg g(-1) for Cd and 0.14
      0.18 microg g(-1) for Hg). Metal distribution in M. libycus proved site-related
      and organ-specific, recognizing a higher affinity of most tested metals towards
      the kidneys, liver and brain than the lung and heart. The comparatively lower
      site-specific accumulation of Pb in soft tissues was attributed primarily to its
      major hypothetical accumulation in bones, whereas, the transition rate of Hg from
      the liver was suggested to be lower to the brain than to the kidneys. Although a
      non hazardous status was assumed for Cu (11.27-13.16 microg g(-1)) and Hg (up to
      0.207 microg g(-1)) in tissues of M. libycus, a potential risk was imposed by
      mean tissue concentrations of Cd (up to 3.29 microg g(01)), Ni (up to 1.48 microg
      g(-1)) and Pb (up to 1.94 microg g(-1)). On the grounds of the significantly
      higher metal levels in polluted soft tissues versus reference subjects, Libyan
      jirds possess high exposure potential and can be useful biomonitors of
      environmental metal contamination.

PMID- 22471222
TI  - Plant stature of aromatic rice genotypes in the environment of Bangladesh.
AB  - Plant stature of a rice crop is an important selection criterion. As plant height
      is a quantitative trait it is influenced by environmental conditions. A field
      experiment was conducted with 40 rice genotypes to assess the fluctuation and
      stability of plant height in a series of 16 environmental situations. The effects
      of genotype (G), environment (E) and all the components of GxE interaction were
      highly significant. Among the genotypes, Jamai sohagi was extremely sensitive (bi
      = 1.37) to environmental changes, and indicating lowest adaptability over the
      environments. Plant height of seven genotypes viz. Basmati PNR346, Benaful,
      BRRIdhan28, BRRIdhan38, BRRIdhan39, Gandho kasturi and Neimat, having the bi
      values between 0.59 and 0.72, showed high stability against environmental
      changes. The otherseven genotypes viz. Badshabhog, Basmati Tapl-90, Kamini soru,
      Khazar, Laljira, Sarwati and Ukni madhu expressed only nonlinear sensitivity
      (S2di = 90-181)) and thus unpredictable fluctuation. Twenty one genotypes
      indicated their average stability (bi = 0.91-1.15) over the environments.

PMID- 22471223
TI  - Uptake and accumulation of potentially toxic metals (Zn, Cu and Pb) in soils and
      plants of Durgapur industrial belt.
AB  - Uptake and accumulation of metals in crops may cause possible health risks
      through food chain. A field survey was conducted to investigate the accumulation
      of potentially toxic metals contamination in soil and plants irrigated with
      complexed industrial effluents. Concentration of Zn, Cu and Pb was 205-255,101
      130,118-177 microg g(-1) in rhizosphere soils and 116-223, 57-102 and 63-95
      microg g(-1) d. wt. in root and 95-186, 44-75 and 27-58 microg g(-1) d. wt. in
      shoot, respectively. The trend in Cu and Pb was in the order: soil > root > shoot
      > seed while in Zn it was soil > root > seed > shoot. Roots accumulated a larger
      fraction of soil Cu (70%) > Zn (67%) > Pb (54%). Bioaccumulation coefficient of
      soil to root ranged from 51-98 for Zn, 54-85 for Cu and 43-63 for Pb.Analysis of
      variance showed marginal change in bioaccumulation coefficient, noticed between
      plants (p > 0.05) while it varied significantly (p < 0.01) between tissues and
      metals. It increased from root to seed/fruit (root > shoot > seed/fruit) while
      decreased between metals from Zn to Pb (Zn > Cu > Pb). Out of the three, two Cu
      and Pb accumulated to phyotoxic levels while Zn was within threshold limit of
      phytotoxicity.

PMID- 22471224
TI  - Study on accumulation ability of two lichen species Hypogymnia physodes and Usnea
      hirta at iron-steel factory site, Turkey.
AB  - The use of biological responses to contaminant exposure by lichen species has
      become a useful tool in environmental quality evaluation and risk assesment.
      Lichen Hypogymnia physodes and Usnea hirta samples were collected in 2006 from 10
      sites around iron-steel factory in Karabuk, Turkey. H. physodes and U. hirta
      samples from Yenice forest were used as a control. The aim of present study was
      to evaluate the bioaccumulation ability and to determine the environmental impact
      of an iron-steel factory in Karabuk. Seven elements (Zn, Cu, Mn, Fe, Pb, Ni, Cr
      and Cd) were analysed by atomic absorption spectrometry (AAS). The analytical
      results were compared statistically by using SPSS. As expected, the study area
      (Yenice forest, Karabuk) chosen as control site (site no 11) showed significantly
      lower impact in comparison to other site (site no 1-10). Compared with the two
      lichen species, H. physodes showed highest metal accumulating capacity while U.
      hirta showed lowest. These criteria attested the best suitability for H.
      physodes, followed by U. hirta.

PMID- 22471225
TI  - Recent advances in human brown fat physiology.
AB  - Of the two variants of adipose tissue, white fat is traditionally known as a
      lipid rich tissue which undergoes pathological expansion in obese conditions. To
      counter the excess accumulation of white fat in states of energy imbalance, the
      second and unique type of brown fat plays a key role by burning extra energy into
      heat through a special metabolic pathway. In addition brown fat also plays a
      vital role in thermoregulation in animals and newborn humans and infants. Recent
      progress in research areas of these two types of fat tissue has provided
      compelling evidence to show that they secrete a large number of chemicals that
      play an important role in body weight control that involves several mechanisms.
      Brown fat was considered absent in the adult humans until recently. But new
      techniques have provided ample support for its active existence. Based on the
      very recent data it has been suggested that brown fat can be a target organ in
      the treatment of obesity which can lead to exciting and informative outcomes in
      the future.

PMID- 22471226
TI  - Effect of curcumin on glucose absorption: an experimental study on albino rats.
AB  - Curcumin derived from the rhizome Curcuma longa is one of the primary ingredient
      in turmeric. Turmeric is used frequently as food additive in Asia, specially the
      Indian subcontinent. The daily intake of turmeric in the diet may therefore
      expose the gut to curcumin and affect its physiological functions, including the
      absorption of nutrients from small intestine. However, no published reports are
      available on the effect curcumin on absorption of nutrients from small intestine.
      To explore this possibility, transport of glucose from small intestine was
      studied in adult albino rats following feeding the animals curcumin
      intragastrically for five consecutive days. The controls were fed simultaneously,
      the vehicular fluid intragastrically in the identical volume. Transport of
      glucose from small intestine was studied using everted sac technique of Wilson
      and Wiseman (1954) on animals fasted for 16-20 hrs. Everted sacs were prepared
      from both jejunal and ileal portion of small intestine. Observations showed a
      significant increase in glucose transport from jejunal and upper ileal portion of
      small intestine suggesting that curcumin does influence the transport of
      nutrients from the gut.

PMID- 22471227
TI  - Protective effect of alpha-tocopheral on biochemical and histological alterations
      induced by cadmium in rat testes.
AB  - Cadmium (Cd) is a potential environmental pollutant and causes severe damage to
      reproductive organs in adults including ovary and testes. Of all antioxidants
      alpha-tocopheral is considered to be most potent chain breaking antioxidant. Our
      aim was to study the effect of alpha-tocopheral on biochemical and histological
      alterations induced by Cd in testes of rats. Group 1 served as control, while
      groups 2 and 3 received subcutaneous injections of CdCl2 (3 mg/kg b.wt) once a
      week for four weeks. Group 3 in addition received alpha-tocopheral (75 mg/kg
      b.wt.) orally, daily for six weeks. Cadmium caused testicular tissue biochemical
      alterations such as significant increase in MDA, a peroxidation marker, decrease
      in antioxidant markers viz SOD, CAT and GSH and functional markers viz ALP and
      LDH. Histological alteration induced by Cd consisted of desquamation of basal
      lamina, shrunken tubules, generalized germ cell depletion with multinucleated
      gaint cells, degenerating Leydig cells, vascular congestion, interstitial edema
      and significant reduction in spermatodynamic count. Alpha-tocopheral
      significantly reversed all the Cd induced alterations. These results indicate
      that alpha-tocopheral has a protective effect against Cd indeed biochemical and
      histological alterations in rat testes.

PMID- 22471228
TI  - Validity of 20 meter multi-stage shuttle run test for estimation of maximum
      oxygen uptake in male university students.
AB  - Direct estimation of cardiorespiratory fitness in terms of VO2max is restricted
      within well equipped laboratory. Eighty four (84) sedentary male university
      students (Age 22.77 +/- 1.73 years, Body height 167.73 +/- 4.07 cm and Body mass
      58.25 +/- 4.02 kg) of same socio-economic background were recruited from students
      of University of Calcutta, Kolkata, India to validate the applicability of 20
      meter shuttle run test (SRT) for indirect estimation of VO2max in young male
      sedentary university students of Kolkata, India. They were further asigned to
      "study group" (N = 54) on which the existing experimental protocol of SRT was
      tested and "confirmatory group" (N = 30) on which the modified equations were
      validated. VO2max of each participant was determined by direct procedure and
      indirect SRT method with a gap of four days in between the tests. The difference
      between the mean values of directly measured VO2max and indirectly predicted
      VO2max (PVO2max) in the "study group" was statistically significant (P < 0.001).
      Limit of agreement analysis revealed poor confidence level for application of
      current method of SRT in the studied population. VO2max was significantly
      correlated with age (r = 0.70, P < 0.001), body mass (r = 0.64, P < 0.001), body
      height (r = 0.58, P < 0.001), speed (r = 0.94, P < 0.001) and PVO2max (r = 0.89,
      P < 0.001). Modified norms in the form of simple and multiple regression
      equations have been computed. Our results suggest that SRT in its original form
      cannot be applied in the young males of Kolkata, India, due to its poor agreement
      with the direct method but is applicable with the modified equations. The SEE of
      these currently proposed norms arc substantially small enough to recommend the
      modified equations in the studied population to evaluate VO2max.

PMID- 22471229
TI  - Effects of obesity on balance and gait alterations in young adults.
AB  - The effects of obesity on the balance and gait parameters like step width and
      foot angle (degree of toe out) in young adults were studied. 60 subjects of both
      the genders were taken. 30 were taken as a control group (non-obese, BMI < 25)
      and 30 were taken as experimental group (obese, BMI 30 >). Functional Reach Test
      (FRT) was used for Balance Testing and the Footprint method was used for Gait
      parameters measurements. The value of functional reach test in females was 11.90
      +/- 0.12 inches in control group and 7.01 +/- 1.80 inches in experimental group
      (t = 5.31, P < 0.001) and in males, it was 16.45 +/- 0.72 inches in control and
      11.66 +/- 0.53 inches in experimental group (t = 6.47, P < 0.001). The degree of
      toe out in females was 6.66 +/- 0.08 degrees for control and 8.13 +/- 0.21
      degrees for experimental group (t = 4.08, P < 0.01) and in males, it was 6.59 +/-
      0.04 for control and 9.79 +/- 0.51 for experimental group (t = 6.53, P < 0.001).
      The step width was found to be 4.41 +/- 0.15 inches (control group) and 6.27 +/-
      0.35 inches (experimental) in males (t = 4.53, P < 0.01) and it was 3.95 +/- 0.03
      inches (control) and 3.42 +/- 1.05 inches (experimental) in females (t = 0.77, P
      > 0.05). We concluded that obesity has a negative impact on balance of an
      individual. The degree of toe out was more in obese group as compared to normal
      BMI group in both genders. The Step Width measurement was more in males of obese
      group than that in males of normal BMI group but it showed statistically
      insignificant when compared in females of both groups.

PMID- 22471230
TI  - Event related potentials in anemic school--going girls of age group 8 to 10
      years.
AB  - In the present study the effects of anemia on cognitive functions were studied in
      school going girls aged 8-10 years. The cognitive functions were assessed by
      Event Related Potentials (P300) and by the psychometric tests, i.e., Raven's
      progressive matrices test and Digit span attention test. The girls with Hb < 12
      g/dl were classified into anemic and Hb > 12 g/dl into control group.
      Hematological values of the control group were significantly better than anemic
      group. P300 latency in the anemic girls was delayed as compared to control group
      but, no statistically significant difference was observed for P300 latency and
      P300 amplitude between the control group and the anemic group. The psychometric
      test scores for intelligence quotient and transformed quotient were also better
      but not statistically significant in control group of girls as compared to anemic
      girls. However, the hematocrit values showed a significant correlation with the
      P300 wave latency showing that the hematological status is associated with some
      effects on cognition.

PMID- 22471231
TI  - Normative data of upper limb nerve conduction in Central India.
AB  - Nerve conduction study is an important tool to evaluate peripheral nerve
      abnormality. The primary purpose of this study was to provide normative
      electrophysiological data for commonly tested upper limb nerves in normal healthy
      adults. Nerve conduction studies were performed prospectively in upper limbs of
      175 carefully screened healthy volunteers between the ages of 18 and 66 years
      using standardized techniques. There was no statistically significant difference
      found in conduction velocity and amplitude of motor median and ulnar nerves as
      well as sensory conduction velocity of median nerve. However, distal and F
      minimum latencies of motor nerves, sensory amplitudes and conduction velocity of
      ulnar nerve was found to be significantly influenced by gender (P < 0.05). This
      study established normative conduction parameters of the commonly tested nerves
      of upper limb for our clinical neurophysiology laboratory in Central India. This
      can be of use to evaluate the patients with peripheral nerve abnormalities who
      reside in this particular geographic set-up. Gender was shown to have an
      influence on sensory amplitude, distal motor and F-minimum latencies of median
      and ulnar nerves.

PMID- 22471232
TI  - Autonomic reactivity to cold pressor test in prehypertensive and hypertensive
      medical students.
AB  - Autonomic reactivity to stress has been hypothesized to be a marker for
      subsequent neurogenic hypertension. Medical training is highly stressful
      particularly for those who are beginning their medical education. The present
      study was undertaken to study the autonomic reactivity to cold pressor test in
      prehypertensive and hypertensive undergraduate medical students. One hundred and
      seventeen undergraduate medical students between 17-21 years of age got examined
      for blood pressure and stress level. Twelve Hypertensives and eight
      prehypertensives selected from the above subjects and twenty normotensives
      underwent cold pressure test (CPT) to assess autonomic reactivity to laboratory
      induced stress. 10.25% of the subjects were found to be hypertensive and 6.83%
      pre hypertensive. On the stress scale 53% had mild stress, 7% showed moderate
      stress while none had stress as a major problem. There was no correlation between
      BP and stress score. On CPT, BP increased significantly in all the three groups
      (hypertensive, prehypertensive and normotensive) but came back to basal levels
      within 5 minutes indicating normal autonomic response. Rise of BP was higher in
      hypertensive group as compared to normotensive group. The rise of diastolic and
      mean BP during CPT was significantly higher in subjects having family history of
      hypertension. Forty percent of normotensive subjects had more than 20 mm Hg rise
      in systolic BP on CPT. Adolescents must be routinely screened to detect
      asymptomatic hypertension. The CPT may identify individuals with an occult
      physiological abnormality that predisposes them to hypertension in their later
      life.

PMID- 22471233
TI  - Heart rate variability in normotensive subjects with family history of
      hypertension.
AB  - Hypertension (HT) is a major silent disease affecting young people because of
      their hereditary and modern lifestyles. Target organ damages occur before overt
      hypertension is diagnosed. Many offspring of HT parents show early changes in
      their cardiovascular autonomic functions. Heart rate variability (HRV) provides a
      window to understand the cardiac autonomic balance. This study was designed to
      quantify and to compare the HRV among the normotensive young male offspring
      without history of parenteral hypertension & diabetic (control group, n = 25, age
      20.8 +/- 2.4, BMI 24.4 +/- 3.1) with parenteral history of hypertension & non
      diabetic (study group n = 25, age 19.7 +/- 1.9, 24.05 +/- 3.5). Blood pressure,
      heart rate (HR), indices of short term HRV during supine rest and quiet standing,
      HR variation during timed controlled deep breathing was compared between the two
      groups. There were significant difference in low frequency (LF) power, HF power,
      total power. LF and HF expressed also in normalized units at rest and standing.
      In time domain standard deviation of normal to normal RR interval (SDNN) at
      supine rest and standing were significant. Respiratory sinus arrthymia (RSA), HF
      in normalized units, deep breathing difference (BDD) and the ratio of maximum RR
      to minimum RR were also significant in the control group than study group. In the
      present study there was an increased sympathetic and decreased parasympathetic
      activity in the study group. These findings are an early marker of cardiovascular
      autonomic impairment in subjects with parenteral history of hypertension.

PMID- 22471234
TI  - Warm sensitive neurons of the preoptic area regulate ambient temperature related
      changes in sleep in the rat.
AB  - Warm sensitive neurons (WSN) play a major role not only in body temperature
      regulation, but also in sleep regulation. The present study was undertaken to
      investigate the role of WSN of the preoptic area (POA) in mediating the ambient
      temperature (T(amb)) related changes in sleep. The effect of T(amb) changes on
      sleep and body temperature was studied in rats before and after destruction of
      WSN of the POA by local intracerebral injection of capsaicin. Though the rats
      preferred 27 degrees C T(amb), they slept maximum at 30 degrees C. After
      destruction of WSN of the POA, slow wave sleep (SWS) peak was brought down to 27
      degrees C, which was the preferred T(amb) of the rats. This indicates that WSN of
      the POA mediate the increase in SWS, at temperatures higher than preferred
      T(amb). On the other hand, in WSN destroyed rats, rapid eye movement (REM) sleep
      was maximum at 33 degrees C. It suggests that the REM sleep generation is under
      inhibitory control of the WSN of the POA. The study supports several earlier
      reports that the neurons of the POA play a key role in coordinating sleep and
      body temperature regulation.

PMID- 22471235
TI  - Drug utilization pattern and effectiveness analysis in diabetes mellitus at a
      tertiary care centre in eastern Nepal.
AB  - An observational follow up study conducted for one year at a tertiary care centre
      in 154 newly diagnosed diabetes mellitus patients is presented. The aims of the
      study were to determine the demographics, prescribing patterns, drug cost and
      analyze effectiveness of different therapies. Effectiveness of therapies were
      analyzed in patients achieving glycemic control by Wilcoxon signed- rank test.
      Majority of patients (n = 114) fell into the middle age strata of 35-64 years and
      97% were type 2 diabetics. A total of 282 prescriptions were screened that
      included antidiabetics and other drug categories. Mean number of drugs per
      prescription sheet was 1.83 +/- 1.31. Oral hypoglycemic agents were advised to
      64% of the patients. The prescribing frequency of biguanides (24.5%) was more
      than sulphonylureas (19.9%). Only 67 patients followed up for 3 months +/- 15
      days, of which 46 achieved glycemic control. The biguanides only group (p =
      0.002) and combination therapy of biguanides and sulphonylureas group (p = 0.005)
      were the highly effective therapies, as their p values of fasting blood glucose
      levels on follow up were the lowest. Nearly 90% of patients on combination
      therapy achieved glycemic control. In conclusion, this study reflects the
      therapeutic approach followed in diabetes mellitus as optimal. Future research on
      a larger patient population is warranted to evaluate existing patterns of therapy
      for sound practice and quality of care.

PMID- 22471236
TI  - Plasma oxidant-antioxidants status in asthma and its correlation with pulmonary
      function tests.
AB  - The present study was planned to asses the levels of oxidant and antioxidant in
      asthmatic patients and to evaluate the existence of correlation between oxidant
      antioxidant levels and pulmonary function test. Asthma is a well know chronic
      inflammatory disorder where disturbances in the oxidative system have been
      observed. To investigate the oxidative stress plasma malondialdehyde and ascorbic
      acid (Vitamin C) were measured. FEV1, FEV1% and PEFR values were taken with
      computerized spirometry. Results revealed statistically significantly reduced PFT
      values (***P < 0.001) in asthmatics. Increase serum MDA (***P < 0.001) and
      decrease vitamin C (***P < 0.001) in patients suggestive of oxidative imbalance
      in asthma was revealed. However no correlation was found between PFT and
      oxidative stress indicators. The study thus supported the emerging concept of
      free radical injury in asthma and therefore a thought can be given to whether
      antioxidant supply could have a beneficial impact on the free radical induced
      injury and improvement of respiratory reserve in Asthmatics.

PMID- 22471237
TI  - A study of relation between body mass index and simple reaction time in healthy
      young females.
AB  - Reaction time is an indirect index of processing capabilities of the central
      nervous system. The present study was carried out to determine if there is any
      influence of body mass index on "simple reaction time in healthy young females.
      In this study, 60 young female participants were allotted to one of the three
      anthropometric groups based on their body mass index (BMI). Their reaction time
      to auditory as well as visual stimuli was recorded. Results were expressed as
      mean, standard deviation and data was analyzed using one - way ANOVA with post
      hoc Tukey's HSD test. Visual as well as auditory reaction time was longer in
      subjects having higher and lower BMI than normal. Visual reaction time was
      significantly longer in subjects with lower BMI as compared to that of subjects
      with normal BMI (P < 0.05). Thus body mass index of an individual affects sensory
      motor association.

PMID- 22471238
TI  - The biocompatibility of metal-organic framework coatings: an investigation on the
      stability of SURMOFs with regard to water and selected cell culture media.
AB  - Highly porous thin films based on a [Cu(bdc)(2)](n) (bdc = benzene-1,4
      dicarboxylic acid) metal-organic framework, MOF, grown using liquid-phase epitaxy
      (LPE) show remarkable stability in pure water as well as in artificial seawater.
      This opens the possibility to use these highly porous coatings for environmental
      and life science applications. Here we characterize in detail the stability of
      these SURMOF 2 thin films under aqueous and cell culture conditions. We find that
      the material degrades only very slowly in water and artificial seawater (ASW)
      whereas in typical cell culture media (PBS and DMEM) a rapid dissolution is
      observed. The release of Cu(2+) ions resulting from the dissolution of the SURMOF
      2 in the liquids exhibits no adverse effect on the adhesion of fibroblasts,
      prototype eukaryotic cells, to the substrate and their subsequent proliferation,
      thus demonstrating the biocompatibility of SURMOF 2 surface coatings. Thus, the
      results are an important step toward application of these porous materials as a
      slow release matrix, for example, for pharmaceuticals and growth factors.

PMID- 22471240
TI  - Impact of thermal processing on sulforaphane yield from broccoli ( Brassica
      oleracea L. ssp. italica).
AB  - In broccoli, sulforaphane forms when the glucosinolate glucoraphanin is
      hydrolyzed by the endogenous plant thiohydrolase myrosinase. A myrosinase
      cofactor directs hydrolysis away from the formation of bioactive sulforaphane and
      toward an inactive product, sulforaphane nitrile. The cofactor is more heat
      sensitive than myrosinase, presenting an opportunity to preferentially direct
      hydrolysis toward sulforaphane formation through regulation of thermal
      processing. Four broccoli cultivars were microwave heated, boiled, or steamed for
      various lengths of time. Production of nitrile during hydrolysis of unheated
      broccoli varied among cultivars from 91 to 52% of hydrolysis products (Pinnacle >
      Marathon > Patriot > Brigadier). Boiling and microwave heating caused an initial
      loss of nitrile, with a concomitant increase in sulforaphane, followed by loss of
      sulforaphane, all within 1 min. In contrast, steaming enhanced sulforaphane yield
      between 1.0 and 3.0 min in all but Brigadier. These data are proof of concept
      that steaming for 1.0-3.0 min provides less nitrile and more sulforaphane yield
      from a broccoli meal. 

PMID- 22471239
TI  - Nanoclusters of iron oxide: effect of core composition on structure,
      biocompatibility, and cell labeling efficacy.
AB  - Inorganic nanocrystals have a variety of applications in medicine. They may serve
      as contrast agents, therapeutics, and for in vitro diagnostics. Frequently, the
      synthesis route yields hydrophobically capped nanocrystals, which necessitates
      their subsequent coating to render a water-soluble and biocompatible probe.
      Biocompatibility is crucial for cellular imaging applications, which require
      large quantities of diagnostically active nanoparticles to be loaded into cells.
      We have previously reported the design and synthesis of a fluorescent and
      magnetic resonance imaging-detectable core-shell nanoparticle that encapsulates
      hydrophobically coated iron oxide nanocrystals. The core of soybean oil and iron
      oxide is covered by a shell mixture of phospholipids, some of which contained
      polyethylene glycol. Despite the biocompatibility of these components, we
      hypothesize that we can improve this formulation with respect to in vitro
      toxicity. To this aim, we measured the effect of six different core compositions
      on nanoparticle structure, cell labeling efficacy, and cell viability, as well as
      cell tracking potential. We methodically investigated the causes of toxicity and
      conclude that, even when combining biocompatible materials, the resulting
      formulation is not guaranteed to be biocompatible. 

PMID- 22471241
TI  - Mutational patterns and novel mutations of the BRAF gene in a large cohort of
      Korean patients with papillary thyroid carcinoma.
AB  - BACKGROUND: BRAF mutation is the most common genetic event in papillary thyroid
      carcinoma (PTC); however, the prevalence and patterns of the mutation vary
      worldwide. We investigated the frequency and type of BRAF mutations based on the
      histologic subtypes in a large cohort of Korean patients with PTC. METHODS: A
      total of 1041 consecutive PTCs were classified according to histologic subtypes.
      BRAF mutations were examined by denaturing high-performance liquid chromatography
      and direct sequencing. Rare complex mutations were confirmed by molecular cloning
      of polymerase chain reaction amplicons and sequencing of the products. RESULTS:
      BRAF mutations were found in 839 (80.6%) of 1041 patients with PTC. The
      histologic subtype-specific prevalence of BRAF mutation was as follows: 85.3%
      (249/292) were classic, 45.8% (11/24) were follicular, 79.9% (576/721) were
      microcarcinoma, and 75.0% (3/4) were other variants. In addition to the usual
      c.1799T>A mutation, we identified other four mutation types:
      c.[1795_1796insA;1770_1795dup26], c.[1742-10T>C;1799T>A] and c.[1796C>G;1799T>A],
      and c.1799_1800TG>AA, respectively. The former three were novel mutations in
      thyroid tumors. Within the series of microcarcinoma variants, the BRAF mutation
      rate was lower in tumors with follicular morphology than those with nonfollicular
      types (66.7% vs. 80.9%, p=0.0145). CONCLUSION: Out of 1041 Korean patients with
      PTC, 0.4% had rare types of BRAF mutation and three new somatic mutations were
      identified. The BRAF mutation rate was quite low in PTC with follicular
      morphology regardless of tumor size. However, the prevalence of BRAF mutation in
      microcarcinoma and follicular variants of PTC is relatively high in Korea and its
      analysis may be clinically useful for managing the patients.

PMID- 22471242
TI  - Papillary thyroid carcinomas with cervical lymph node metastases can be
      stratified into clinically relevant prognostic categories using oncogenic BRAF,
      the number of nodal metastases, and extra-nodal extension.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) patients presenting with cervical
      lymph nodes (LN) metastases (M) have a variable outcome. The objective of this
      study is to assess the value of meticulous histopathologic examination and
      genotyping in stratifying these patients into clinically relevant prognostic
      subgroups. METHODS: This was a retrospective clinical and histopathological
      review of PTC patients with lymph node metastases at presentation identified
      between 1980 and 2002 in a single institution. Primary tumors from patients who
      later recurred were matched to a group of patients who did not recur and
      subjected to mass spectrometry genotyping encompassing the most significant
      oncogenes in thyroid carcinomas. RESULTS: There were 246 patients who satisfied
      the inclusion criteria. The median follow-up was 10.8 years. The presence of >3
      metastatic nodes was an independent predictor of decreased recurrence free
      survival (p=0.03). In patients <45 years, none of 45 with 1-2 metastatic LN
      recurred, including 26 patients followed for a median of 13 years without
      radioactive iodine (RAI) therapy. BRAF mutations were found in 28 (78%) of 36
      genotyped tumors. Combined positivity for BRAF and extra-nodal extension was much
      stronger in predicting disease specific survival (DSS) (p=0.004) than the single
      analysis of BRAF (p=0.12) or extra-nodal extension (p=0.02). CONCLUSIONS: (i) The
      number of metastatic LN is an independent predictor of recurrence in all age
      groups and identifies a subset of young patients with excellent prognosis who may
      not benefit from RAI therapy. (ii) Combined positivity for BRAF and extra-nodal
      extension has additive prognostic value in predicting DSS. (iii) Classification
      systems that assign the same magnitude of risk for recurrence or death to all
      patients with N1 disease should be revisited.

PMID- 22471243
TI  - The expanding role of endoscopic skull base surgery.
AB  - The endoscopic endonasal approach (EEA) is a surgical technique where a small
      aperture, the nostrils, can give access to the whole ventral skull base. Its
      principles differ from the ones of traditional skull base approaches where a wide
      external opening is often accompanied by a relatively small working area. Most of
      the results of EEAs published in the literature come from retrospective case
      series and the follow-up is still limited, however the consensus is that this
      technique is safe and effective in selected cases and when performed within
      dedicated skull base centres. This article sets to give an overview of the
      current state of endoscopic skull base surgery, based on the recent evidence and
      our centre's experience with nearly 2000 EEAs. The team's experience with
      endoscopic as well as open approaches plays a critical role in achieving
      satisfactory results when treating pathologies of the skull base. Guided by the
      principle of least neural and vascular manipulation, the team should be able to
      select the least traumatic route (open or endoscopic) and be able to approach the
      skull base from all angles.

PMID- 22471244
TI  - Melanoma tumor seeding after punch biopsy.

PMID- 22471245
TI  - Single molecule kinetics of ENTH binding to lipid membranes.
AB  - Transient recruitment of proteins to membranes is a fundamental mechanism by
      which the cell exerts spatial and temporal control over proteins' localization
      and interactions. Thus, the specificity and the kinetics of peripheral proteins'
      membrane residence are an attribute of their function. Here, we describe the
      membrane interactions of the interfacial epsin N-terminal homology (ENTH) domain
      with its target lipid phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P(2)).
      The direct visualization and quantification of interactions of single ENTH
      molecules with supported lipid bilayers is achieved using total internal
      reflection fluorescence microscopy (TIRFM) with a time resolution of 13 ms. This
      enables the recording of the kinetic behavior of ENTH interacting with membranes
      with physiologically relevant concentrations of PtdIns(4,5)P(2) despite the low
      effective binding affinity. Subsequent single fluorophore tracking permits us to
      build up distributions of residence times and to measure ENTH dissociation rates
      as a function of membrane composition. Furthermore, due to the high time
      resolution, we are able to resolve details of the motion of ENTH associated with
      a simple, homogeneous membrane. In this case ENTH's diffusive transport appears
      to be the result of at least three different diffusion processes.

PMID- 22471246
TI  - Effects of herpes simplex virus type 1 infection on immune functions of human
      neutrophils.
AB  - BACKGROUND AND OBJECTIVE: Herpesviruses may play roles in the development of
      periodontal diseases. This study analyzed the effects of herpes simplex virus
      type 1 (HSV-1) infection on neutrophil function. The effects of
      lipopolysaccharide (LPS) from the periodontal pathogen, Porphyromonas gingivalis,
      during HSV-1 infection were also determined. MATERIAL AND METHODS: Purified HSV-1
      was pretreated with buffer containing no serum, with HSV-1 immunoglobulin G (IgG)
      positive serum (HSV-1 antiserum) or with control serum. Neutrophils were mock
      infected or infected with the pretreated HSV-1. Viral binding and phagosome
      formation were detected using immunostaining. Intracellular reactive oxygen
      species (ROS) were determined using 2',7'-dichlorofluorescin diacetate and
      fluorometry. Leukotriene B(4) (LTB(4)) and interleukin-8 (IL-8) were detected
      using enzyme immunoassays. Release of matrix metalloproteinase-9 (MMP-9) was
      examined using gelatin zymography. Phosphorylation of Akt/glycogen synthase
      kinase-3 (GSK-3) was determined using western blotting. RESULTS: HSV-1 bound
      directly to neutrophils and enhanced the release of MMP-9. HSV-1 immune
      complexes, formed in the HSV-1 antiserum, bound neutrophils and induced the
      formation of early phagosome more effectively than did HSV-1 alone. The relative
      levels of ROS and phosphorylation of Akt/GSK-3 were increased significantly in
      neutrophils after infection with HSV-1 immune complexes. Infection with HSV-1 and
      HSV-1 immune complexes also stimulated the production of inflammatory mediators,
      LTB(4) and IL-8. Moreover, LPS enhanced the HSV-1-stimulatory production of IL-8.
      CONCLUSION: This study demonstrated differences in neutrophils infected with HSV
      1 alone or with HSV-1 immune complexes, suggesting that opsonization of HSV-1
      might enhance its effects on neutrophils. The in vitro findings suggest that HSV
      1 infection may induce the inflammatory response and affect periodontal health.

PMID- 22471247
TI  - Biosimilar recombinant human erythropoietins ("epoetins") and future
      erythropoiesis-stimulating treatments.
AB  - INTRODUCTION: Recombinant human erythropoietin (rhEPO, epoetin) has prospered in
      the treatment of renal and chemotherapy-associated anemias. Since the patents of
      the original epoetins expired, biosimilars have been launched. Because these are
      not fully identical to the original products, non-clinical and clinical studies
      are necessary to show similarity with respect to quality, safety, and efficacy.
      AREAS COVERED: The article summarizes experiences with EU-approved biosimilar
      epoetins. In particular, the issue of immunogenicity is considered. Neutralizing
      anti-EPO antibodies can cause pure red cell aplasia (PRCA). Further, a first view
      is offered on future erythropoiesis-stimulating therapies. EXPERT OPINION: The
      term "biosimilar" should only be used for follow-on biopharmaceuticals approved
      under a defined regulatory pathway. The primary rationale for the therapy with
      biosimilars is cost saving. Two biosimilar epoetins are available in the EU that
      are used at the same dose(s) and dosing regimen(s) for indications of the
      reference product. Their advent has stimulated innovator companies to develop
      second-generation products with improved pharmacokinetic properties. EPO
      mimicking peptides are a new therapeutic option. Other strategies focus on orally
      active chemical drugs that induce endogenous EPO production ("HIF stabilizers").
      Epo gene transfer is also possible, but needs to be further explored with respect
      to efficacy and safety.

PMID- 22471248
TI  - Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl
      peptidase-4 inhibitors as add-on therapy to metformin in subjects with type 2
      diabetes-a review and meta analysis.
AB  - AIMS: During recent years, two strategies of incretin-based therapy [glucagon
      like peptide-1 (GLP-1) receptor agonism and dipeptidyl peptidase-4 (DPP-4)
      inhibition] have entered the market for pharmacological management of type 2
      diabetes. A main indication for this therapy is as add-on to on-going metformin
      therapy in subjects with type 2 diabetes who have insufficient glycaemic control
      with metformin alone. The aim of this study was to compare improvements in
      glycaemic control and changes in body weight, as well as adverse events, in
      comparable studies with incretin-based therapy as add-on to metformin. METHODS:
      Studies having a duration of 16-30 weeks were identified from PubMed. RESULTS: A
      total of 27 study groups in 21 studies fulfilled the criteria of examining
      incretin-based therapy as add-on to metformin at clinically recommended doses in
      patients with type 2 diabetes for 16-30 weeks; 7 of these used a short-acting GLP
      1 receptor agonist (exenatide BID), 7 used longer acting GLP-1 receptor agonists
      (liraglutide or exenatide LAR), whereas 14 studies examined DPP-4 inhibitors. In
      all studies, incretin-based therapy reduced HbA1c concentrations. The reduction
      in HbA1c was significantly greater in study groups with long-acting GLP-1
      receptor agonists than with the other two groups (both p < 0.001), whereas there
      were no differences between exenatide BID and DPP-4 inhibitors. Across all study
      groups, there was a negative linear correlation between baseline HbA1c and change
      in HbA1c (r = -0.70; p < 0.001). Fasting glucose also fell significantly more in
      study groups given liraglutide or exenatide LAR than in those given exenatide BID
      or DPP-4 inhibitors (both p < 0.001). Furthermore, body weight was reduced by a
      similar extent in the two groups with GLP-1 receptor agonists and was not
      significantly altered in the groups with DPP-4 inhibitors. Lipids, blood pressure
      and heart rate were not reported consistently, which did not allow general
      conclusions. Adverse events were rare, apart from increased incidence of nausea
      and vomiting with GLP-1 receptor agonists. CONCLUSION: Incretin-based therapy
      efficiently improves glycaemia when added to metformin in patients with type 2
      diabetes, and within 16-30 weeks there is a more pronounced reduction in HbA1c
      with long-acting GLP-1 receptor agonists (liraglutide and exenatide LAR) than
      with exenatide BID and DPP-4 inhibitors, although the magnitude of the effect is
      dependent on the baseline values. Both strategies appear to be associated with a
      very low risk of adverse events, including hypoglycaemia. Finally, the injectable
      GLP-1 receptor agonists also reduce body weight (whereas the DPP-4 inhibitors are
      weight neutral) but are also associated with a greater incidence of
      gastrointestinal side effects and a tendency to increase heart rate.

PMID- 22471249
TI  - Significant evidence for a heritable contribution to cancer predisposition: a
      review of cancer familiality by site.
AB  - BACKGROUND/AIMS: Sound and rigorous well-established, and newly extended, methods
      for genetic epidemiological analysis were used to analyze population evidence for
      genetic contributions to risk for numerous common cancer sites in Utah. The Utah
      Population Database (UPDB) has provided important illumination of the familial
      contribution to cancer risk by cancer site. METHODS: With over 15 years of new
      cancer data since the previous comprehensive familial cancer analysis, we tested
      for excess familial clustering using an expanded Genealogical Index of
      Familiality (dGIF) methodology that provides for a more informative, but
      conservative test for the existence of a genetic contribution to familial
      relatedness in cancer. RESULTS: Some new cancer sites have been analyzed for the
      first time, having achieved sufficiently large sample size with additions to the
      UPDB. This new analysis has identified 6 cancer sites with significant evidence
      for a heritable contribution to risk, including lip, chronic lymphocytic
      leukemia, thyroid, lung, prostate, and melanoma. CONCLUSIONS: Both
      environmentally and genetically-based familial clustering have clinical
      significance, and these results support increased surveillance for cancer of the
      same sites among close relatives of affected individuals for many more cancers
      than are typically considered.

PMID- 22471250
TI  - Importance of mesenchymal stem cells in autologous fat grafting: a systematic
      review of existing studies.
AB  - Autologous fat grafting (lipofilling) enables repair and augmentation of soft
      tissues and is increasingly used both in aesthetic and reconstructive surgery.
      Autologous fat has several advantages, including biocompatibility, versatility,
      natural appearance, and low donor site morbidity. The main limitation is
      unpredictable graft resorption, which ranges from 25%-80%, probably as a result
      of ischaemia and lack of neoangiogenesis. To obviate these disadvantages, several
      studies have searched for new ways of increasing the viability of the
      transplanted tissue. One promising approach has been to enrich the fat graft with
      adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We
      have reviewed original studies published on fat transplantation enriched with
      ASC. We found four murine and three human studies that investigated the subject
      after a sensitive search of publications. In the human studies, so-called cell
      assisted lipotransfer (CAL) increased the ASC concentration 2-5 times compared
      with non-manipulated fat grafts, which caused a questionable improvement in
      survival of fat grafts, compared with that of traditional lipofilling. In
      contrast, in two of the murine studies ASC-concentrations were increased 1250 and
      6250 times, respectively, by ASC ex vivo expansion, which resulted in
      considerably improved fat transplant survival as well as quality. This effect of
      high-level enrichment with ASC is thought to have been caused by paracrine
      signalling, cellular differentiation, or both. The surgical and tissue handling
      techniques used in lipofilling are well proved, but the added effect of high
      level enrichment with ex vivo expanded ASC still needs to be investigated
      properly in human lipofilling studies, combined with a thorough follow up and
      matched control groups. In conclusion, ASC-enriched lipofilling theoretically has
      the potential for transforming lipofilling from a relatively unpredictable
      intervention into one in which the resorption rate, quality of tissue, and safety
      can be predicted, and possibly superior to prosthetic implantation.

PMID- 22471252
TI  - Prenatal ultrasound detection of cleft lip, or cleft palate, or both, in southern
      Sweden, 2006-2010.
AB  - It has been possible to detect cleft lip (CL), with or without cleft palate
      (CLP), using ultrasound (US) since the beginning of the 1980s. The aim of this
      study was to assess the accuracy of prenatal diagnosis of cleft lip with or
      without cleft palate, and isolated cleft palate (ICP), in our catchment area.
      Screening protocols in the different US clinics in southern Sweden were also
      compared, as regards evaluation of the fetal face and prenatal diagnosis of CLP.
      Forty-four (31%) of the patients were diagnosed by prenatal US and 97/144 (67%)
      were diagnosed at birth. The detection rate was 44/102 (43%) if the ICP are
      excluded. The specificity was 100%. Among the prenatally diagnosed clefts, 25/44
      (57%) were diagnosed before the gestational age of 20 weeks. In 19/44 (43%) of
      the cases the US diagnosis of cleft was accurate in the light of the postnatal
      outcome. All US departments in our catchment area follow the Swedish guidelines
      and offer one routine US examination during the second trimester between 18 and
      20 weeks of pregnancy. In addition, many of the clinics offer an additional US
      examination during the third trimester. Our detection rate is similar to previous
      findings. The detection rates and the accuracy of the prenatal diagnosis can be
      improved. To achieve this, an increased focus on detecting clefts, standardising
      scanning plans, and rescans in case of incomplete facial views, are essential.

PMID- 22471253
TI  - Adopted children with cleft lip or palate, or both, require special needs cleft
      surgery.
AB  - In recent years adoption of children with cleft lip, with or without cleft palate
      (CLP), and other birth defects has become more common. The aim of the present
      study was to describe the characteristics and initial care and treatment of
      adopted children with CLP. A total of 25 children were referred to our department
      between 2008 and 2010, 7 (28%) of whom had bilateral CLP and 16 (64%) had
      unilateral CLP. Two children had atypical clefts. Twenty of the patients (80%)
      had been operated on with a lip plasty in China before adoption. Most patients (n
      = 14) was seen by the cleft team within two months of arrival, and 13 were
      operated on within a month of the first visit at our department. In total, 22
      primary palatoplasties, 6 lip plasties, and 1 lip adhesion were done. There were
      5 fistulas (14%) three months after the palatoplasty. On arrival, 11 (44%) of the
      children were carriers of methicillin-resistant Staphylococcus aureus (MRSA).
      Adoption of children with CLP creates new challenges for the cleft teams, as we
      no longer have control over the overall treatment plan as regards preoperative
      and surgical treatment and timing of the operations. The patients are also often
      carriers of resistant bacteria, which create nursing challenges. In cases where
      the child is older than a year and has not been operated on, we advocate that the
      palatoplasty, or combined lip plasty and palatoplasty, is always given priority
      so that speech development is not compromised.

PMID- 22471254
TI  - Aesthetic reconstruction of a defect in the skin of the upper lip using a hatchet
      flap.
AB  - Reconstruction of the upper lip requires symmetrical reconstruction of the free
      border according to the aesthetic principle. We have reconstructed this area with
      a hatchet flap, so that the scars match the subunit line as far as possible by
      rotation and advancement of the flap. We operated on six patients. The lower
      pedicled flap was used in 4 cases and the upper pedicled flap in 2, who also
      needed reconstruction of the vermillion. In one patient the scar did not match
      the nasolabial fold. For the upper pedicled cases, scars made on the vermillion
      were not conspicuous. However, trap door deformity occurred in half, which was a
      disadvantage. We think that our flap is useful, because it leaves a minimal scar
      in an inconspicuous area.

PMID- 22471255
TI  - Improved shape and consistency after lipofilling of the breast: patients'
      evaluation of the outcome.
AB  - Autologous transplantation of fat, or lipofilling, of the breast can correct
      deformities after reconstruction and after conservation surgery for cancer. We
      have made a retrospective evaluation of morbidity and patients' experiences of
      the method. Forty-four patients have had lipofilling once, twice, or three times
      (mean transplanted volume 40 ml, range 6-200 ml). One minor complication, a local
      infection, was treated with antibiotics given orally, and recorded at follow up.
      A questionnaire was sent to all 44 patients and answered by 43. Twenty-nine of
      the 43 patients reported improvement of irregularities after lipofilling, 26
      reported that the shape of the breast had improved, 26 that the consistency had
      improved, and 20 that the size had increased postoperatively. Five of the
      patients reported some adverse effects; one case of liponecrosis that did not
      need any treatment was found one year postoperatively. No problems were reported
      at the donor site at follow-up.

PMID- 22471256
TI  - Anterior rectus fascia back cut: a new modification to relieve the pressure in
      fascial closure of the superior pedicle of a transverse rectus abdominis
      myocutaneous flap.
AB  - The maintenance of vascular patency is one of the key points to be considered
      after a pedicled transverse rectus abdominis myocutaneous (TRAM) flap has been
      raised and when closing the anterior rectus fascia to avoid a hernia. In this
      study we describe a new approach to closing the most superior part of the fascia
      to help insure vascular patency. Forty patients who had their breasts
      reconstructed with TRAM flaps made up the study group. The new back cut technique
      was used in 25 patients. Of the remaining 15 patients, four required early
      revision on the day of operation for severe venous congestion or ischaemia. None
      of the patients who had the back cut technique required early revision. We found
      the back cut technique to be safe and easy, and we think that it can reduce the
      incidence of flap ischaemia and still achieve tight fascial closure.

PMID- 22471257
TI  - Formation of hypertrophic scars: evolution and susceptibility.
AB  - Formation of hypertrophic scars is a common complication of wound healing, and at
      present little is known about the incidence and risk factors. Our aim was to
      analyse the incidence, progression, and regression of postoperative hypertrophic
      scars over time and to identify risk factors of hypertrophic scars. Patients who
      had had bilateral reduction mammoplasty or median sternotomy incision were
      included in the study. All patients were examined at 3 and 12 months
      postoperatively. We recorded: height, weight, allergy status, smoking status,
      skin type, tanning, and shape of the scar 3 and 12 months postoperatively. Of the
      204 patients who were included, 122 (60%) developed a hypertrophic scar within 12
      months of operation. Of these patients, 117 (96%) developed a hypertrophic scar
      within 3 months of operation. Twelve months postoperatively, 66/204 patients
      (32%) had a hypertrophic scar. In 31 of the 66 of the patients with a
      hypertrophic scar 3 months postoperatively (47%), the hypertrophic scar(s)
      regressed after 3 and 12 months. Smoking and age were associated with formation
      of hypertrophic scars. In conclusion, 60% of patients developed hypertrophic
      scars postoperatively, typically during the first three months. Most hypertrophic
      scars that are present after three months are still hypertrophic after 12 months.
      Young, non-smoking patients are more susceptible to formation of hypertrophic
      scars.

PMID- 22471258
TI  - Validation of Biodex system 4 for measuring the strength of muscles in patients
      with rectus diastasis.
AB  - To investigate the validity and reliability of the Biodex system 4 in the
      assessment of abdominal strength in patients with rectus diastasis, we studied 10
      healthy volunteers and 10 patients with rectus diastasis of more than 3 cm. We
      assessed test-retest reliability at 30(o) and 60(o) of extension/flexion spinal
      angles, respectively, and isometric muscle strength with and without the
      abdominal girdle. Reliability was calculated using the interclass correlation
      coefficient (ICC). Validity was evaluated by correlation with the International
      Physical Activity Questionnaire (IPAQ) and a visual analogue scale (VAS) for self
      assessment of abdominal muscular strength. The Kendall-Tau and Spearman tests
      were used. Reliability was excellent with ICC values ranging between 0.77 and
      0.97. There was no significant difference in muscular strength for tests with or
      without a girdle except with 60(o) extension. The internal validity assessed as
      the correlation between VAS and isometric strength (p = 0.008) was excellent,
      whereas there was no correlation with IPAQ. The Biodex system 4 is a valuable and
      reliable instrument to measure abdominal wall strength in patients with rectus
      diastasis. The internal validity is excellent. The incongruence between abdominal
      muscle strength, as measured using the Biodex system 4, and IPAQ indicates that
      there is no relation between general physical activity (IPAQ) and muscular
      strength in patients with rectus diastasis.

PMID- 22471259
TI  - Cerebral changes after injury to the median nerve: a long-term follow up.
AB  - Injury to the peripheral nerves in the upper extremity results in changes in the
      nerve, and at multiple sites throughout the central nervous system (CNS). We
      studied the long-term effects of an injury to the median nerve in the forearm
      with a focus on changes in the CNS. Four patients with isolated injuries of the
      median nerve in their 20s were examined a mean of 14 years after the injury.
      Cortical activation was monitored during tactile stimulation of the fingers of
      the injured and healthy hand using functional magnetic resonance imaging at 3
      Tesla. The neurophysiological state and clinical outcome were also examined.
      Activation in the primary somatosensory cortex was substantially larger during
      tactile stimulation of the injured hand than with stimulation of the uninjured
      hand. We also saw a redistribution of hemispheric dominance. Stimulation of the
      injured median nerve resulted in a substantially increased dominance of the
      contralateral hemisphere. However, stimulation of the healthy ulnar nerve
      resulted in a decreased dominance of the contralateral hemisphere.
      Neurophysiology showed low sensory amplitudes, velocity, and increased motor
      latency in the injured nerve. Clinically there were abnormalities predominately
      in the sensory domain. However, there was an overall improved mean result
      compared with a five year follow-up in the same subjects. The cortical changes
      could be the result of cortical reorganisation after a changed afferent signal
      pattern from the injured nerve. Even though the clinical function improved over
      time it did not return to normal, and neither did the cortical response.

PMID- 22471260
TI  - Reconstruction of the trapeziometacarpal joint in inflammatory joint disease
      using interposition of autologous tendon or poly-L-D-lactic acid implants: a
      prospective clinical trial.
AB  - Interposition arthroplasty with bioreplaceable poly-L-D-lactic acid (PLDLA)
      implants has yielded promising results in reconstruction of rheumatoid hands. In
      this prospective clinical study we compared the PLDLA implant arthroplasty (n =
      17) with that of tendon interposition (n = 12) for destruction of the
      trapeziometacarpal joint in arthritic patients. There was no significant
      difference between the two groups preoperatively. At one-year follow-up, the mean
      pain and function scores were 5 and 13 in the PLDLA group, and 19 and 43 in the
      tendon interposition group, respectively. At one-year follow-up the visual
      analogue scale (VAS) for function of the PLDLA group differed significantly from
      that of the tendon interposition group (p = 0.03). This difference was not found
      at three months postoperatively, and disappeared again at two-year follow-up.
      Otherwise, no significant difference was found between the groups in the pain or
      function scores, functional tests, or range of movement. Bioreplaceable
      interposition arthroplasty works at least as well as tendon interposition. The
      operation is easier.

PMID- 22471261
TI  - Dendritic fibromyxolipoma adherent to the median nerve in the forearm.
AB  - We describe a 65-year-old woman with a tumour adherent to the median nerve in the
      left forearm that was found to be a dendritic fibromyxolipoma, a distinctive
      benign soft tissue lesion possibly related to a myxoid spindle cell lipoma; it is
      a solitary fibrous tumour that may be mistaken for a sarcoma. The tumour was
      successfully excised with no complications.

PMID- 22471262
TI  - Carpal tunnel syndrome caused by a fibrolipomatous hamartoma of the median nerve
      treated by endoscopic release of the carpal tunnel.
AB  - Fibrolipomatous hamartoma has up to now been considered a rare anomaly that most
      commonly affects the median nerve. Its pathogenesis is controversial. The
      magnetic resonance (MR) appearance is pathognomonic and precludes the necessity
      for a diagnostic biopsy. Its reported incidence is likely to increase as a result
      of the increased use of MRI. There is no definitive treatment, although carpal
      tunnel syndrome caused by fibrolipomatous hamartoma has been noted to respond to
      open release of the carpal tunnel. We describe a case of carpal tunnel syndrome
      caused by fibrolipomatous hamartoma of the median nerve that responded to a two
      port endoscopic technique of release. Provided that a safe, distinct surgical
      plane can be established between the median nerve and the flexor retinaculum, the
      two-port technique of endoscopic release of the carpal tunnel is both safe and
      effective.

PMID- 22471263
TI  - Regional first web flap used to cover the amputated stump of the thumb.
AB  - The regional first web flap is a distally-based flap that is raised from the
      radiodorsal aspect of the metacarpophalangeal joint of the index finger towards
      the dorsal first web, and used to cover a thumb amputation. The advantage of this
      flap over the conventional cross-finger flap is that is gives a thicker and
      hairless flap with no skin graft to the donor site. Mobilisation of the joints,
      including the metacarpophalangeal joint of the index finger, can also be
      maintained during the immobilisation period between two stages.

PMID- 22471264
TI  - Treatment of a large aneurysmal bone cyst in a 15-year-old boy using a
      corticospongial bone graft and a 12-year follow-up after operation.
AB  - We report the case of a 15-year-old boy with a large aneurysmal bone cyst in the
      third metacarpal, which was operated on radically with excision of the bone and
      grafting from the distal radius. At 12-year follow-up the patient had good
      cosmetic results and a perfectly functioning hand.

PMID- 22471265
TI  - A phase I study of daily treatment with a ceramide-dominant triple lipid mixture
      commencing in neonates.
AB  - BACKGROUND: Defects in skin barrier function are associated with an increase risk
      of eczema and atopic sensitisation. Ceramide-dominant triple lipid mixture may
      improve and maintain the infant skin barrier function, and if shown to be safe
      and feasible, may therefore offer an effective approach to reduce the incidence
      of eczema and subsequent atopic sensitisation. We sort to assess the safety and
      compliance with daily application of a ceramide-dominant triple lipid formula
      (EpiCeramTM) commencing in the neonatal period for the prevention of eczema.
      METHODS: Ten infants (0-4 weeks of age) with a family history of allergic disease
      were recruited into an open-label, phase one trial of daily application of
      EpiCeramTM for six weeks. The primary outcomes were rate of compliance and
      adverse events. Data on development of eczema, and physiological properties of
      the skin (transepidermal water loss, hydration, and surface pH) were also
      measured. RESULTS: Eighty percent (8/10) of mothers applied the study cream on
      80% or more of days during the six week intervention period. Though a number of
      adverse events unrelated to study product were reported, there were no adverse
      skin reactions to the study cream. CONCLUSIONS: These preliminary results support
      the safety and parental compliance with daily applications of a ceramide-dominant
      formula for the prevention of eczema, providing the necessary ground work for a
      randomised clinical trial to evaluate EpiCeramTM for the prevention of eczema.
      TRIAL REGISTRATION: The study was listed at the Australian/New Zealand Clinical
      Trial Registry (ANZCTR): reg. no. ACTRN12609000727246.

PMID- 22471275
TI  - Strict stereocontrol by 2,4-O-di-tert-butylsilylene group on beta
      glucuronylations.
AB  - Strict beta-controlled glucuronylations without classical neighboring-group
      participation were achieved by the assistance of a 2,4-O-di-tert-butylsilylene
      group. Comparison of activation conditions and conformational analysis indicated
      that the strict beta-selectivity was achieved by steric hindrance of the 2,4-O-di
      tert-butylsilylene group and not by complex glycosyl intermediates.

PMID- 22471276
TI  - Acute inpatient presentation of kwashiorkor: not just a diagnosis of the
      developing world.
AB  - We present the case of an infant with presumed Stevens-Johnson syndrome. Through
      a history, physical, and histopathology, we were able to diagnose the patient
      with kwashiorkor. Physicians should be aware of this disorder, which is commonly
      thought of as a developing world problem, because it is increasing in incidence
      in industrialized nations because of changing dietary habits. 

PMID- 22471277
TI  - Tumour necrosis factor-mediated macrophage activation in the target organ is
      critical for clinical manifestation of uveitis.
AB  - Clinically available anti-tumour necrosis factor (TNF) biologics, which inhibit
      both soluble (sTNF) and transmembrane forms (tmTNF) of TNF, eliminating all TNF
      signalling, have successfully treated autoimmune diseases including uveitis.
      These have potentially serious side effects such as reactivation of latent
      Mycobacterium tuberculosis and, therefore, more specific inhibition of TNF
      signalling pathways may maintain clinical efficacy while reducing adverse
      effects. To determine the effects of specific pharmacological inhibition of sTNF
      on macrophage activation and migration, we used a mouse model of uveitis
      (experimental autoimmune uveoretinitis; EAU). We show that selective inhibition
      of sTNF is sufficient to suppress EAU by limiting inflammatory CD11b(+)
      macrophages and CD4(+) T cell migration into the eye. However, inhibition of both
      sTNF and tmTNF is required to inhibit interferon-gamma-induced chemokine receptor
      2, CD40, major histocompatibility complex class II and nitric oxide (NO) up
      regulation, and signalling via tmTNF is sufficient to mediate tissue damage. In
      confirmation, intravitreal inhibition of sTNF alone did not suppress disease, and
      inflammatory cells that migrated into the eye were activated, generating NO, thus
      causing structural damage to the retina. In contrast, intravitreal inhibition of
      both sTNF and tmTNF suppressed macrophage activation and therefore disease. We
      conclude that sTNF is required for inflammatory cell infiltration into target
      tissue, but at the tissue site inhibition of both sTNF and tmTNF is required to
      inhibit macrophage activation and to protect from tissue damage.

PMID- 22471278
TI  - Murine lupus strains differentially model unique facets of human lupus serology.
AB  - Systemic lupus erythematosus (SLE) is a polygenic autoimmune disease
      characterized by the production of anti-nuclear autoantibodies that lead to
      subsequent end organ damage. Previous array-based studies in patients with SLE
      have shown that high immunoglobulin (Ig)G anti-nuclear autoantibody reactivity
      was associated with severe renal lupus, whereas IgM polyreactivity was associated
      with less severe disease. To ascertain how different murine lupus strains
      recapitulate these different autoantibody profiles seen in patients, serum from
      New Zealand black (NZB)/NZ white (W) F(1), Murphy Roths large (MRL)/lpr, NZ mixed
      (M)2410 and BXSB strains were compared using a comprehensive array-based screen.
      The array results were verified using enzyme-linked immunosorbent assays
      (ELISAs). Serum from MRL/lpr mice exhibited high levels of IgG anti-nuclear
      antibodies as well as anti-glomerular antibodies and variable levels of
      antibodies to myosin, Matrigel and thyroglobulin. Elevated anti-nuclear IgG
      antibodies were associated with severe nephritis in this strain. In contrast,
      NZM2410 mice exhibited lower IgG autoantibody levels with less severe nephritis
      but a significantly higher polyreactive IgM autoantibody profile. ELISA analysis
      confirmed these results. The NZB/NZW F(1) and BXSB strains exhibited an
      intermediate serological profile. Hence, just as in patients with SLE, whereas
      strong IgG reactivity to nuclear antigens is associated with severe renal
      disease, a polyreactive IgM seroprofile is also less ominous in murine lupus.

PMID- 22471279
TI  - Prognostic importance of tumour-infiltrating memory T cells in oesophageal
      squamous cell carcinoma.
AB  - Memory T cells survive for many months and years and are critically important for
      host defence in humans. In tumour immunity, they have been also suggested to play
      a significant role in tumour progression and metastasis. However, the role of
      memory T cells in actual human cancer remains largely unknown. In this study, the
      clinical importance of tumour-infiltrating CD45RO(+) memory T cells was
      investigated in human oesophageal squamous cell carcinoma (OSCC). CD45RO(+) T
      cells were evaluated by immunohistochemistry in primary OSCC tumours from 105
      patients. Patients were classified into two groups as CD45RO(+hi) or CD45RO(+lo)
      based on the number of cells stained positively for CD45RO. No significant
      difference was observed between CD45RO status and several clinicopathological
      prognostic factors. However, the postoperative overall and disease-free survival
      for CD45RO(+hi) patients was significantly better than for CD45RO(+lo) patients.
      Furthermore, there were significant correlations of CD45RO status in the primary
      tumour with postoperative lymph node and pulmonary recurrence, suggesting that
      memory T cells may control postoperative metastatic recurrence. Most importantly,
      CD45RO(+) memory T cell status has a significant prognostic value for OSCC
      independently of conventional tumour-node-metastasis (TNM) classification. Our
      study may provide a rationale for developing a novel immunotherapy in intentional
      induction of memory T cells for the treatment of oesophageal cancer.

PMID- 22471280
TI  - Pro-tumour activity of interleukin-22 in HPAFII human pancreatic cancer cells.
AB  - Interleukin (IL)-22 is a cytokine involved in inflammatory and wound healing
      processes that is secreted primarily by T helper type 17 (Th17) cells. IL-22
      receptor (IL-22R) expression is limited to epithelial cells of the digestive
      organs, respiratory tract and skin. Most tumours originating in these sites over
      express IL-22R. Interestingly, there is an increase in Th17 frequency within the
      peripheral blood and tumour microenvironment of advanced cancer patients.
      Subsequently, IL-17 has been shown to display both pro-tumour and anti-tumour
      functions. Because many tumours lack expression of the IL-17 receptor, the
      effects of IL-17 on tumour growth are generated by cells that surround the tumour
      cells. Like IL-17, high levels of IL-22 have been detected in tumour tissues and
      the peripheral blood of cancer patients; however, the direct effect of IL-22 on
      tumour cells has remained largely unknown. In this report, we show that IL-22
      stimulated production of vascular endothelial growth factor (VEGF) and the anti
      apoptotic factor Bcl-X(L) in IL-22R-positive HPAFII human pancreatic cancer
      cells. Additionally, IL-22 augmented HPAFII cell production of immunosuppressive
      cytokines. We show further that IL-22 activation of HPAFII cells diminished T
      cell production of interferon (IFN)-gamma through the action of IL-10.
      Strikingly, we show for the first time that IL-22 can fully protect cancer cells
      from natural killer (NK) cell-mediated cytotoxicity by stimulating tumour
      production of IL-10 and transforming growth factor (TGF)-beta1. Our data support
      the idea that IL-22 may act to promote the pathogenesis of cancers rather than
      function in anti-tumour immunity.

PMID- 22471281
TI  - Functionality of CD4+ and CD8+ T cells from tonsillar tissue.
AB  - For many years, tonsillectomy has been used routinely in children to treat
      chronic or recurrent acute tonsillitis. Palatine tonsils are secondary lymphoid
      organs and the major barrier protecting the digestive and respiratory tracts from
      potential invasive microorganisms. They have been used as sources of lymphoid
      tissue; however, despite the hundreds of papers published on tonsillectomy, no
      studies addressing the functionality of the CD4(+)  and CD8(+)  T cells from
      chronically infected tonsils have yet been published. The aim of this study was
      to analyse the functionality of the CD4(+)  and CD8(+)  T cells with respect to
      tonsillar tissue. We used an affordable approach to measure the frequency of
      antigen-specific CD4(+)  T cells, the direct ex-vivo cytotoxicity of CD8(+)  T
      cells, memory T cell phenotype, cytokine profile and DC phenotype. Our results
      demonstrate that CD4(+)  and CD8(+)  T cells from tonsillar tissue are totally
      functional, as shown by their ability to produce cytokines, to degranulate and to
      differentiate into effector-memory T cells.

PMID- 22471282
TI  - Increased peripheral blood CD4+ T cell responses to deamidated but not to native
      gliadin in children with coeliac disease.
AB  - T cell recognition of gliadin from dietary gluten is essential for the
      pathogenesis of coeliac disease (CD). The aim of the present study was to analyse
      whether gliadin-specific T cells are detectable in the circulation of children
      with newly diagnosed coeliac disease by using a sensitive carboxfluorescein
      diacetate succinimidyl ester (CFSE) dilution method. Peripheral blood CD4(+) T
      cell responses were analysed in 20 children at diagnosis of CD and compared to
      those in 64 healthy control children carrying the CD-associated human leucocyte
      antigen (HLA)-DQ2 or -DQ8 alleles. Deamidated gliadin (gTG)-specific T cells were
      detectable in the peripheral blood of more than half the children with CD (11 of
      20, 55%) compared to 15 of 64 (23.4%) of the control children (P = 0.008).
      Proliferative responses to gTG were also significantly stronger in children with
      CD than in controls (P = 0.01). In contrast, T cells specific to native gliadin
      were detectable at comparable frequencies in children with CD (two of 19, 10.5%)
      and controls (13 of 64, 20.3%). gTG-specific T cells had a memory phenotype more
      often than those specific to native gliadin in children with CD (P = 0.02),
      whereas controls had similar percentages of memory cells in both stimulations.
      Finally, gTG-specific CD4(+) T cells had a higher expression of the gut-homing
      molecule beta7 integrin than those specific to the control antigen tetanus
      toxoid. Collectively, our current results demonstrate that the frequency of
      circulating memory CD4(+) T cells specific to gTG but not native gliadin is
      increased in children with newly diagnosed CD.

PMID- 22471283
TI  - Identification of serotype-specific T cell responses to highly conserved regions
      of the dengue viruses.
AB  - Determining previous infecting dengue virus (DENV) serotypes has been difficult
      due to highly cross-reactive immune responses from previous DENV infections.
      Determining the correlates of serotype-specific immune responses would be crucial
      in understanding dengue transmission in the community and would also help to
      determine the correlates of protective immune responses. Therefore, we set out to
      define highly conserved, serotype-specific regions of the DENVs. Serotype
      specific and highly conserved regions of the four DENV serotypes were identified
      using Basic Local Alignment Search Tool (BLAST) searches and custom perl scripts.
      Using ex-vivo and cultured enzyme-linked immunospot (ELISPOT) assays, we
      identified serotype-specific T cell epitopes within the four DENV serotypes in
      healthy adult donors from Sri Lanka. We identified T cell responses to 19 regions
      of the four DENV serotypes. Six peptides were from the NS2A region and four
      peptides were from the NS4A region. All immune donors responded to peptides of at
      least two DENV serotypes, suggesting that heterologous infection is common in Sri
      Lanka. Eight of 20 individuals responded to at least two peptides of DENV-4,
      despite this serotype not being implicated previously in any of the epidemics in
      Sri Lanka. The use of these regions to determine past and current infecting DENV
      serotypes will be of value to characterize further the dynamics of silent dengue
      transmission in the community. In addition, these T cell responses to these
      regions could be used to characterize DENV serotype-specific immune responses and
      thus possibly help us to understand the immune correlates of a protective immune
      response.

PMID- 22471284
TI  - Altered frequency and phenotype of CD4+ forkhead box protein 3+ T cells and its
      association with autoantibody production in human immunodeficiency virus-infected
      paediatric patients.
AB  - The association between immune dysfunction and the development of autoimmune
      pathology in patients with human immunodeficiency virus/acquired immune
      deficiency syndrome (HIV/AIDS) is not clear. The frequency and phenotype of
      regulatory T cells, as well as the presence of autoantibodies, were evaluated in
      a paediatric cohort of HIV-infected patients without clinical evidence of
      autoimmune disease. Lower absolute counts but higher percentages of total CD4(+)
      forkhead box protein 3 (FoxP3)(+) T cells were recorded in children with severe
      immunosuppression than in those without evidence of immunosuppression. The
      frequencies of classical CD4(+) CD25(+) FoxP3(+) regulatory T cells were not
      altered, whereas CD4(+) FoxP3(+) CD25(-) T cells were found increased
      significantly in patients with severe immunosuppression. Like classical
      regulatory T cells, CD4(+) FoxP3(+) CD25(-) T cells display higher cytotoxic T
      lymphocyte antigen 4 (CTLA-4) but lower CD127 expression compared with CD4(+)
      FoxP3(-) CD25(+) T cells. An improvement in CD4(+) T cell counts, along with a
      decrease in viral load, was associated with a decrease in CD4(+) FoxP3(+) CD25(-)
      T cells. The majority of the patients with severe immunosuppression were positive
      for at least one out of seven autoantibodies tested and displayed
      hypergammaglobulinaemia. Conversely, HIV-infected children without evidence of
      immunosuppression had lower levels of autoantibodies and total immunoglobulins. A
      decline in CD4(+) FoxP3(+) T cell numbers or a variation in their phenotype may
      induce a raise in antigen exposure with polyclonal B cell activation, probably
      contributing to the generation of autoantibodies in the absence of clinical
      autoimmune disease.

PMID- 22471285
TI  - Inhibitory effect of statins on inflammatory cytokine production from human
      bronchial epithelial cells.
AB  - Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of
      cholesterol biosynthesis, and have been reported to exert pleiotropic effects on
      cellular signalling and cellular functions involved in inflammation. Recent
      reports have demonstrated that previous statin therapy reduced the risk of
      pneumonia or increased survival in patients with community-acquired pneumonia.
      However, the precise mechanisms responsible for these effects are unclear. In the
      present study, we examined the effects of statins on cytokine production from
      lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B).
      Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS
      stimulated cells were inhibited significantly by the lipophilic statin
      pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects
      of statin were negated by adding mevalonate, the anti-inflammatory effects of
      statins appear to be exerted via the mevalonic cascade. In addition, the
      activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured
      with pitavastatin were significantly lower than those without the statin. These
      results suggest that statins have anti-inflammatory effects by reducing cytokine
      production through inhibition of the mevalonic cascade followed by RhoA
      activation in the lung.

PMID- 22471286
TI  - Characteristics of alloreactive T cells measured before renal transplantation.
AB  - Several assays to measure pre-existing allospecific T cell immunity in renal
      transplant candidates have been developed in the past years. In 46 patients, we
      used flow cytometry-based mixed lymphocyte culture to measure the precursor
      frequency and phenotype of alloreactive T cells before renal transplantation,
      using donor-specific or third-party cells for allostimulation. Allostimulation
      induced up-regulation of co-stimulatory molecules, chemokine receptors relevant
      for migration of T cells into the graft and effector proteins. Recipients prone
      for acute rejection had a higher precursor frequency of alloreactive CD8(+)  T
      cells and a lower percentage of interleukin (IL)-7Ralpha expressing alloreactive
      CD8(+)  T cells than non-rejectors. These data point to quantitative and
      qualitative differences between T cells of patients who will experience acute
      cellular rejection episodes from those who will not.

PMID- 22471288
TI  - Question-behaviour effect: a randomised controlled trial of asking intention in
      the interrogative or declarative form.
AB  - OBJECTIVE: This study investigated the question-behaviour effect of measuring
      intention in the interrogative or declarative form combined or not with a measure
      of moral norm. DESIGN: A sample of 762 participants was randomised according to a
      2 * 2 factorial design. MAIN OUTCOME MEASURES: Cognitions were assessed at the
      baseline, and physical activity behaviour was self-reported three weeks later.
      RESULTS: At baseline, there were no significant differences on the studied
      variables. An ANOVA showed a significant interaction effect between the two
      experimental conditions (p = 0.04). Post-hoc contrast analyses showed that the
      interrogative intention-only condition significantly differed from the
      declarative intention-only (d = 0.21, p = 0.03) and interrogative intention +
      moral norm (d = 0.22, p = 0.03) conditions. CONCLUSION: Results suggest that self
      posed questions about a future action increases the likelihood of doing it when
      these questions are not accompanied by measures of moral norm. This provides
      support for using introspective self-talk to favour the adoption of behaviour.

PMID- 22471287
TI  - Cyclosporin but not everolimus inhibits chemokine receptor expression on CD4+ T
      cell subsets circulating in the peripheral blood of renal transplant recipients.
AB  - The peripheral chemokine receptors chemokine receptor 3 (CXCR3) and CC chemokine
      receptor 5 (CCR5) have been reported to be associated with allograft rejection.
      The impact of the expression of immunosuppressive drugs on peripherally
      circulating CD4(+) T cell subsets after renal transplantation is unknown.
      Expression of CXCR3 and CCR5 was investigated by flow cytometry in 20 renal
      allograft recipients participating in a prospective, randomized trial
      (NCT00514514). Initial immunosuppression consisted of basiliximab, cyclosporin A
      (CsA), mycophenolate sodium and corticosteroids. After 3 months, patients were
      treated either with CsA, mycophenolate sodium (MPA) plus corticosteroids (n = 6),
      CsA and everolimus plus corticosteroids (n =8) or CsA-free (CsA(free)) receiving
      everolimus, MPA and corticosteroids (n = 6). After initial reduction of CD4(+)
      forkhead box protein 3 (FoxP3)(+) and CD4(+) CD25(hi) FoxP3(+) regulatory T cells
      (T(regs)) (P < 0.05; P < 0.01), 3-month post-transplant percentages of T(regs)
      were reconstituted in CsA(free) and CsA(lo) arms compared to CsA(reg) 12 months
      post transplant. Expression of CCR5 and CXCR3 on CD4(+) FoxP3(+) and CD4(+)
      FoxP3(-) T cells 12 months post transplant was increased in CsA(free) versus
      CsA(reg). Increase in CCR5(+) CXCR3(+) co-expressing CD4(+) FoxP3(-) cells
      between 3 and 12 months correlated negatively with the glomerular filtration rate
      (GFR) slope/year [modification of diet in renal disease (MDRD); r = -0.59, P <
      0.01]. CsA, but not everolimus, inhibits both T(reg) development and expression
      of CXCR3 and CCR5 on CD4(+) T cell subsets. Increase in CCR5(+) CXCR3(+) co
      expressing CD4(+) FoxP3(-) T cells is associated with early loss in allograft
      function.

PMID- 22471289
TI  - Phenotypic plasticity, QTL mapping and genomic characterization of bud set in
      black poplar.
AB  - BACKGROUND: The genetic control of important adaptive traits, such as bud set, is
      still poorly understood in most forest trees species. Poplar is an ideal model
      tree to study bud set because of its indeterminate shoot growth. Thus, a full-sib
      family derived from an intraspecific cross of P. nigra with 162 clonally
      replicated progeny was used to assess the phenotypic plasticity and genetic
      variation of bud set in two sites of contrasting environmental conditions.
      RESULTS: Six crucial phenological stages of bud set were scored. Night length
      appeared to be the most important signal triggering the onset of growth
      cessation. Nevertheless, the effect of other environmental factors, such as
      temperature, increased during the process. Moreover, a considerable role of
      genotype * environment (G * E) interaction was found in all phenological stages
      with the lowest temperature appearing to influence the sensitivity of the most
      plastic genotypes.Descriptors of growth cessation and bud onset explained the
      largest part of phenotypic variation of the entire process. Quantitative trait
      loci (QTL) for these traits were detected. For the four selected traits (the
      onset of growth cessation (date2.5), the transition from shoot to bud (date1.5),
      the duration of bud formation (subproc1) and bud maturation (subproc2)) eight and
      sixteen QTL were mapped on the maternal and paternal map, respectively. The
      identified QTL, each one characterized by small or modest effect, highlighted the
      complex nature of traits involved in bud set process. Comparison between map
      location of QTL and P. trichocarpa genome sequence allowed the identification of
      13 gene models, 67 bud set-related expressional and six functional candidate
      genes (CGs). These CGs are functionally related to relevant biological processes,
      environmental sensing, signaling, and cell growth and development. Some strong
      QTL had no obvious CGs, and hold great promise to identify unknown genes that
      affect bud set. CONCLUSIONS: This study provides a better understanding of the
      physiological and genetic dissection of bud set in poplar. The putative QTL
      identified will be tested for associations in P. nigra natural populations. The
      identified QTL and CGs will also serve as useful targets for poplar breeding.

PMID- 22471291
TI  - Update on the keratoconus genetics.
AB  - Keratoconus (KC) is one of the leading causes for keratoplasty. While the genetic
      aetiology of more and more corneal dystrophies is revealed, KC falls behind. And
      it is not because of lack of effort. The diversity in the many published results
      from over two decades is discussed in relation to the present knowledge in
      molecular biology. Results that at first appear to be in conflict with each other
      make sense when placed in the right context. Ophthalmologists often refer to KC
      as a heterogeneous disease. This review demonstrates that it truly is a
      multifactorial disease. Despite the many attempts to reveal the aetiology of KC,
      the pathological mechanism(s) still remain to be solved.

PMID- 22471290
TI  - The recovery of platelet cyclooxygenase activity explains interindividual
      variability in responsiveness to low-dose aspirin in patients with and without
      diabetes.
AB  - BACKGROUND: Interindividual variability in response to aspirin has been
      popularized as 'resistance'. We hypothesized that faster recovery of platelet
      cyclooxygenase-1 activity may explain incomplete thromboxane (TX) inhibition
      during the 24-h dosing interval. OBJECTIVE: To characterize the kinetics and
      determinants of platelet cyclooxygenase-1 recovery in aspirin-treated diabetic
      and non-diabetic patients. PATIENTS/METHODS: One hundred type 2 diabetic and 73
      non-diabetic patients on chronic aspirin 100 mg daily were studied. Serum TXB(2)
      was measured every 3 h, between 12 and 24 h after a witnessed aspirin intake, to
      characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with
      the fastest TXB(2) recovery were randomized to aspirin 100 mg once daily, 200 mg
      once daily or 100 mg twice daily, for 28 days and TXB(2) recovery was reassessed.
      RESULTS AND CONCLUSIONS: Platelet TXB(2) production was profoundly suppressed at
      12 h in both groups. Serum TXB(2) recovered linearly, with a large
      interindividual variability in slope. Diabetic patients in the third tertile of
      recovery slopes (>= 0.10 ng mL(-1) h(-1) ) showed significantly higher mean
      platelet volume and body mass index, and younger age. Higher body weight was the
      only independent predictor of a faster recovery in non-diabetics. Aspirin 100 mg
      twice daily completely reversed the abnormal TXB(2) recovery in both groups.
      Interindividual variability in the recovery of platelet cyclooxygenase activity
      during the dosing interval may limit the duration of the antiplatelet effect of
      low-dose aspirin in patients with and without diabetes. Inadequate thromboxane
      inhibition can be easily measured and corrected by a twice daily regimen.

PMID- 22471292
TI  - New avenues of research on multiple sclerosis from the perspective of chronic
      cerebrospinal venous insufficiency paradigm.

PMID- 22471293
TI  - Toward an equation of state for water inside carbon nanotubes.
AB  - Water inside carbon nanotubes as an example of nanoconfined water has gained
      noticeable attention, in both theoretical and applied aspects. Molecular
      simulation has played a major role in the studies in this field. Yet, there is a
      need for systematic study of simulation results and compilation of scientifically
      reliable predictive relations. Here we present Monte Carlo simulations of water
      inside carbon nanotubes with different radii. An equation of state which was
      derived on the basis of the extended Lennard-Jones (12,6,3) as the effective pair
      potential is chosen for the system of water inside the carbon nanotubes. The
      equation of state is modified to take the effects of anisotropic pressure tensor
      into account. Using the simulation results, the applicability of this equation of
      state for water inside the carbon nanotubes is studied and the parameters of the
      equation of state for this system are obtained. 

PMID- 22471294
TI  - Lysosomal delivery of a lipophilic gemcitabine prodrug using novel acid-sensitive
      micelles improved its antitumor activity.
AB  - Stimulus-sensitive micelles are attractive anticancer drug delivery systems.
      Herein, we reported a novel strategy to engineer acid-sensitive micelles using a
      amphiphilic material synthesized by directly conjugating the hydrophilic
      poly(ethylene glycol) (PEG) with a hydrophobic stearic acid derivative (C18)
      using an acid-sensitive hydrazone bond (PHC). An acid-insensitive PEG-amide-C18
      (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine
      (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the
      micelles, and they were found to be significantly more cytotoxic to tumor cells
      than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles.
      Moreover, GemC18 in the acid-sensitive PHC micelles was more cytotoxic than in
      the acid-insensitive PAC micelles, which may be attributed to the acid-sensitive
      release of GemC18 from the PHC micelles in lysosomes. In B16-F10 melanoma-bearing
      mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activity than
      GemC18 or gemcitabine solution, likely because of the prolonged circulation time
      and increased tumor accumulation of the GemC18 by the micelles. Importantly, the
      in vivo antitumor activity of GemC18-loaded PHC micelles was significantly
      stronger than that of the PAC micelles, demonstrating the potential of the novel
      acid-sensitive micelles as an anticancer drug delivery system. 

PMID- 22471295
TI  - Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard
      gelatin capsules: results of two phase I trials.
AB  - BACKGROUND: Vinflunine is a new-generation microtubule inhibitor, which is
      currently registered in Europe and in some countries elsewhere as an intravenous
      formulation for the second-line treatment of transitional urothelial cell
      carcinoma. On the basis of favourable non-clinical results, the clinical
      development of an oral formulation was initiated. OBJECTIVE: The absolute oral
      bioavailability was investigated in patients through two consecutive trials: the
      first trial used soft gelatin capsules filled with solubilized vinflunine
      (SLCaps), while the second study investigated hard gelatin capsules containing
      vinflunine as a formulated powder (HPCaps). STUDY DESIGN: Each pharmacokinetic
      trial was conducted according to a randomized cross-over design. Patients
      received 120 mg/m2 of either oral (SLCaps or HPCaps) or intravenous vinflunine on
      day 1, followed by the alternate dosing route after a 2-week washout period.
      Blood samples were collected over 168 hours. A pharmacokinetic analysis was
      conducted for each patient and route of dosing to derive the absolute oral
      bioavailability of SLCaps and HPCaps. RESULTS: A total of 12 and 22 patients were
      enrolled, for SLCaps and HPCaps, respectively. Vinflunine absorption was rapid
      for both oral formulations. Blood concentrations peaked at 2.5 hours following
      oral intake with food, and then decreased similarly to the intravenous profile.
      The mean absolute bioavailability was high, at 58.3 +/- 14.4% (SLCaps) and 57.3
      +/- 11% (HPCaps), with limited inter-individual variability (coefficient of
      variation = 25% and 19% for SLCaps and HPCaps, respectively). Neither sequence
      nor period effects were detected. The gastro-intestinal tolerance was
      satisfactory. The main drug-related adverse events were asthenia, fatigue,
      constipation and neutropenia, mostly of grade 1 or 2. No grade 4 and no drug
      related serious adverse events were reported. CONCLUSION: The high
      bioavailability and low inter-individual variability are favourable
      pharmacokinetic properties, which could be valuable for further clinical
      development of oral vinflunine.

PMID- 22471296
TI  - Inhibitory effects of chloroform extracts derived from Corbicula fluminea on the
      release of pro-inflammatory cytokines.
AB  - Corbicula fluminea, the primary freshwater bivalve cultivated in Taiwan, was
      formerly used as a remedy for hepatitis. Recent reports indicate that C. fluminea
      has many bioactivities, but it remains unknown whether C. fluminea affects
      inflammation. This study explored the anti-inflammatory activity of C. fluminea.
      C. fluminea was first treated with chloroform to obtain clam chloroform extracts
      (CCEs). On the basis of the assay for the release of pro-inflammatory cytokines
      in vitro and in vivo, the results show that the CCEs significantly lowered the
      release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines.
      Additionally, the CCEs reduced LPS-induced organ damage. Real-time polymerase
      chain reaction analysis suggested that CCEs inhibit the LPS-induced mRNA
      expression of interleukin-1beta and tumor necrosis factor-alpha. Western blot
      analysis indicated that the CCEs increased expression of IkappaB and attenuated
      the phosphorylation of IkappaB. Gas chromatography-mass spectrometry suggests
      that phytosterols and fatty acids are responsible for the anti-inflammatory
      properties of CCEs. Taken together, CCEs have the potential to be developed as an
      anti-inflammatory functional food.

PMID- 22471299
TI  - Characterization of periostin expression in human endometrium and endometriotic
      lesions.
AB  - OBJECTIVE(S): To investigate the expression of periostin in the eutopic and
      ectopic endometrium of women diagnosed as endometriosis and evaluate the role of
      periostin in the pathogenesis of endometriosis. STUDY DESIGN: In this study, the
      expression of periostin was evaluated in the endometrial specimens from 35 women
      diagnosed as endometriosis and from 30 healthy women. To assess the presence and
      localization of periostin throughout the menstrual cycle in both eutopic and
      ectopic endometrium of women with endometriosis, microscopic evaluation was
      conducted. It was also subsequently compared with normal endometrium. RESULTS: In
      the eutopic and ectopic endometrium of women with endometriosis,
      immunoreactivities of periostin increased compared with those of normal
      endometrium. We also observed a cyclic variation in the eutopic stromal periostin
      immunoreactivity throughout their menstrual cycle because higher H score values
      were observed in the proliferative phase than those in the secretory phase.
      CONCLUSION(S): These findings indicated that periostin may be involved in the
      pathophysiology of endometriosis.

PMID- 22471300
TI  - Ethanol self-administration in free-flying honeybees (Apis mellifera L.) in an
      operant conditioning protocol.
AB  - BACKGROUND: This study examines the effect of ethanol (EtOH) on continuous
      reinforcement schedules in the free-flying honeybee (Apis mellifera L.). As
      fermented nectars may be encountered naturally in the environment, we designed an
      experiment combining the tools of laboratory research with minimal disturbance to
      the natural life of honeybees. METHODS: Twenty-five honeybees were trained to fly
      from their colonies to a fully automated operant chamber with head poking as the
      operant response. Load size, intervisit interval, and interresponse times (IRTs)
      served as the dependent variables and were monitored over the course of a daily
      training session consisting of many visits. Experimental bees were tested using
      an ABA design in which sucrose only was administered during condition A and a 5%
      EtOH sucrose solution was administered during condition B. Control bees received
      sucrose solution only. RESULTS: Most bees continued to forage after EtOH
      introduction. EtOH significantly reduced the load size and the intervisit
      interval with no significant effect on IRTs. However, a look on individual data
      shows large individual differences suggesting the existence of different kinds of
      behavioral phenotypes linked to EtOH consumption and effects. CONCLUSIONS: Our
      results contribute to the study of EtOH consumption as a normal phenomenon in an
      ecological context and open the door to schedule-controlled drug self
      administration studies in honeybees.

PMID- 22471301
TI  - A comparison of the clinical determinants of health-related quality of life and
      subjective well-being in long-term breast cancer survivors.
AB  - Research concerning long-term breast cancer survivors (BCS) has primarily
      analysed their health-related quality of life (HRQoL). However, other dimensions
      of life considered important by patients might be affected by cancer treatments
      as well. The aim of this paper is thus to compare the clinical determinants of
      HRQoL and of overall quality of life as described by measures of subjective well
      being (SWB) in long-term BCS. SWB represents a person's own evaluation of their
      overall situation. A total of 321 French BCS diagnosed 5 to 15 years ago
      participated in a cross-sectional mailed survey. Outcome measures were the
      physical and mental health scores of the 36-item Short-Form survey and measures
      of SWB (happiness, life satisfaction and the positive and negative affect
      scales). Multivariate regression analyses suggest that HRQoL and SWB measures
      provide different pictures of the experience of breast cancer. Treatment type has
      no impact on HRQoL but is correlated with all our SWB measures while time since
      diagnosis positively affects physical health but not SWB. We conclude that it
      could be fruitful to analyse SWB, alongside the traditional study of HRQoL, in
      order to enhance our understanding of the various long-lasting consequences of
      breast cancer.

PMID- 22471302
TI  - Dose- and time-dependent effects of recombinant human bone morphogenetic protein
      2 on the osteogenic and adipogenic potentials of alveolar bone-derived stromal
      cells.
AB  - BACKGROUND AND OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP
      2) is a well-known growth factor that can induce robust bone formation, and
      recent studies have shown that rhBMP-2-induced osteogenesis is closely related to
      adipogenesis. The aim of the present study was to determine the dose- and time
      dependent effects of rhBMP-2 on the osteogenic and adipogenic differentiation of
      human alveolar bone-derived stromal cells (hABCs) in vivo and in vitro. MATERIAL
      AND METHODS: hABCs were isolated and cultured, and then transplanted using a
      carrier treated either with or without rhBMP-2 (100 MUg/mL) into an ectopic
      subcutaneous mouse model. Comprehensive histologic and histometric analyses were
      performed after an 8-wk healing period. To further understand the dose-dependent
      (0, 10, 50, 200, 500 and 1000 ng/mL) and time-dependent (0, 3, 5, 7 and 14 d)
      effects of rhBMP-2 on osteogenic and adipogenic differentiation, in vitro
      osteogenic and adipogenic differentiation of hABCs were evaluated, and the
      expression of related mRNAs, including those for alkaline phosphatase,
      osteocalcin, bone sialoprotein, peroxisome-proliferator-activated receptor gamma
      2 and lipoprotein lipase, were assessed using quantitative RT-PCR. RESULTS: rhBMP
      2 significantly promoted the osteogenic and adipogenic differentiation of hABCs
      in vivo, and gradually increased both the osteogenic and adipogenic potential in
      a dose- and time-dependent manner with minimal deviation in vitro. The expression
      of osteogenesis- and adipogenesis-associated mRNAs were concomitantly up
      regulated by rhBMP-2. CONCLUSION: The findings of the present study showed that
      rhBMP-2 significantly enhanced the adipogenic as well as the osteogenic potential
      of hABCs in dose- and time-dependent manner. The control of adipogenic
      differentiation of hABCs should be considered when regenerating the alveolar bone
      using rhBMP-2.

PMID- 22471303
TI  - Prospective memory, emotional valence, and multiple sclerosis.
AB  - Cognitive impairments in multiple sclerosis (MS) extend to tasks demanding
      prospective memory (PM): remembering to perform an intended act during ongoing
      activity. This study investigated whether emotional content influenced the
      effects of MS on PM, following evidence that emotional valence can influence
      other aspects of memory. Thirty participants with MS were compared to 30 controls
      on a PM task, Virtual Week, in which emotion was manipulated. People with MS
      showed a consistent deficit in PM performance across manipulations of task and
      valence. Results indicated that emotionally positive tasks improved the PM
      performance of MS participants, with implications for rehabilitation.

PMID- 22471304
TI  - Chondro-osteolipoma of the hand.

PMID- 22471305
TI  - Obesity-associated insulin resistance is correlated to adipose tissue vascular
      endothelial growth factors and metalloproteinase levels.
AB  - BACKGROUND: The expansion of adipose tissue is linked to the development of its
      vasculature, which appears to have the potential to regulate the onset of
      obesity. However, at present, there are no studies highlighting the relationship
      between human adipose tissue angiogenesis and obesity-associated insulin
      resistance (IR). RESULTS: Our aim was to analyze and compare angiogenic factor
      expression levels in both subcutaneous (SC) and omentum (OM) adipose tissues from
      morbidly obese patients (n = 26) with low (OB/L-IR) (healthy obese) and high
      (OB/H-IR) degrees of IR, and lean controls (n = 17). Another objective was to
      examine angiogenic factor correlations with obesity and IR.Here we found that
      VEGF-A was the isoform with higher expression in both OM and SC adipose tissues,
      and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans.
      This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the
      contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in
      both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated
      positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in
      both SC and OM. CONCLUSION: We hereby propose that the alteration in MMP15, VEGF
      B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose
      tissue processes related to the development of IR, and the up-regulation of VEGF
      A in adipose tissue could have a relationship with the prevention of this
      pathology.

PMID- 22471306
TI  - Neutrophilic dermatosis caused by azathioprine hypersensitivity.

PMID- 22471307
TI  - Heme binds to factor VIII and inhibits its interaction with activated factor IX.
AB  - BACKGROUND: Heme is a redox active macrocyclic compound that is released upon
      tissue damage or hemorrhages. The extracellular release of large amounts of heme
      saturates scavenging heme-binding proteins. Free heme has been proposed to affect
      coagulation and has been co-purified with the factor VIII (FVIII)-von Willebrand
      factor (VWF) complex. The sites from which heme is released upon injury overlap
      with the sites to which FVIII is targeted for performing its hemostatic
      functions. OBJECTIVES: To investigate the interaction of heme with FVIII and the
      consequence for the procoagulant activity of FVIII in vitro. METHODS AND RESULTS:
      Heme bound to several sites on FVIII with high apparent affinity. Heme-binding
      inhibited FVIII procoagulant activity in a dose-dependent manner. FVIII
      inactivation in the presence of saturating amounts of heme implicated a reduced
      interaction of FVIII with activated FIX, as shown by ELISA, surface plasmon
      resonance and fluorescence quenching. Heme-mediated inactivation of FVIII was
      prevented by VWF, but not by human serum albumin, a heme-binding protein known
      for its protective activity in hemolytic conditions. CONCLUSIONS: Our data
      identify FVIII as a novel heme-binding protein. Occupation of high affinity heme
      binding sites on FVIII at low concentrations of free heme did not inactivate
      FVIII. Conversely, large molar excesses of heme over FVIII, which correspond to
      conditions of extensive heme release, inhibited FVIII activity in vitro. It
      remains to be demonstrated whether, under such conditions, heme-mediated
      modulation of the activity of FVIII plays some role in the regulation of
      coagulation.

PMID- 22471308
TI  - Nanomedicine for intracellular therapy.
AB  - Intracellular pathogens like Salmonella evade host phagocytic killing by various
      mechanisms. Classical antimicrobial therapy requires multiple dosages and
      frequent administration of drugs for a long duration. Intracellular delivery of
      antimicrobials using nanoparticle may effectively devise therapies for bacterial
      infections. This review will address the mechanisms used by Salmonella to avoid
      host pathogenic killing, reasons for therapeutic failure and advances in
      nanoparticle drug delivery technology for efficient intracellular bacterial
      clearance.

PMID- 22471309
TI  - Conserved functional surface of antimammalian scorpion beta-toxins.
AB  - Scorpion beta-toxins bind to the voltage-sensing domain of voltage-gated sodium
      (NaV) channels and trap the voltage-sensing domain in the activated state. Two
      structurally similar beta-toxins from scorpions, Css4 and Cn2, selectively target
      different subtypes of mammalian NaV channels. While the receptor site on the
      channels is known, the functional surface of the toxins remains to be understood.
      Here, we predict the binding modes of Css4 and Cn2 to the voltage-sensing domains
      of NaV1.2 and NaV1.6, respectively, with a molecular docking method and molecular
      dynamics simulations. The dissociation constants for the predicted toxin-channel
      complexes derived with umbrella sampling simulations are in accord with
      experiment. Our calculations suggest that the functional surface of Cn2 and Css4
      is primarily formed by the loop between positions 8 and 18, centered on the two
      charged residues Lys13 and Glu15. 

PMID- 22471310
TI  - Treatment cost of invasive fungal disease (Ifd) in patients with acute
      myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German
      hospitals.
AB  - Invasive fungal disease (IFD) causes increasing morbidity and mortality in
      haematological cancer patients. Reliable cost data for treating IFD in German
      hospitals is not available. Objective of the study was to determine the
      institutional cost of treating the IFD. Data were obtained by retrospective chart
      review in German hospitals. Patients had either newly diagnosed or relapsed acute
      myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost
      was calculated from hospital provider's perspective. A total of 108 patients were
      enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast
      majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On
      average, the hospital stay for IFD patients was 12 days longer than in control
      patients. All patients in the IFD group and 89% of patients in the control group
      received antifungal drugs. Mean direct costs per patient were ?51,517 in the IFD
      group and ?30,454 in the control group. Incremental costs of ?21,063 were
      dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood
      products (23%). From the perspective of hospitals in Germany the economic burden
      of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD
      is necessary with respect to both clinical and economic reasons.

PMID- 22471311
TI  - Eyelid skin disinfecting and conjunctival bacteria in cataract surgery.
AB  - PURPOSE: To evaluate the effect on conjunctival micro-organisms of chlorhexidine
      alcohol 0.5% eyelid wash in cataract patients. METHODS: In this single-centre
      experimental study, 120 patients scheduled to undergo cataract operation were
      cultured in the conjunctiva before the operation and after the insertion of the
      intraocular lens. Bacterial samples for aerobic and anaerobic cultures were taken
      with a polyvinyl alcohol pad and transported in peptone water to the
      microbiological laboratory where they were analysed in a blinded fashion. Half of
      the patients received a standardized eyelid scrub with chlorhexidine alcohol
      0.5%, while the rest did not. The conjunctiva of all patients was rinsed
      preoperatively with chlorhexidine solution 0.05%. RESULTS: In all the between
      group comparisons, the treated eyelid group had slightly lower bacterial counts
      than the control group on the postoperative samples, but differences were far
      from statistically significant. Within-group comparisons revealed statistically
      significant reduction in colonies and species between the preoperative and
      postoperative sampling. CONCLUSION: In this experimental culture study, no
      evidence was found to suggest that preoperative eyelid chlorhexidine alcohol wash
      is effective in further reducing bacterial counts in the conjunctiva when the
      conjunctiva itself is rinsed preoperatively with chlorhexidine solution. The
      present results, however, do not contradict that the wash may be of some marginal
      help in reducing bacterial contamination of the operation field. Consequently,
      this part of the prophylactic protocol is still in practice in our institution.

PMID- 22471312
TI  - CT evaluation for 'quiescent' herniation following closure of diverting loop
      ileostomy.
AB  - AIM: The prevalence of abdominal wall herniation at the site of a previous
      temporary stoma is uncertain. This cohort study investigated the frequency of
      radiological abnormalities at the site of a closed diverting loop ileostomy.
      METHOD: All patients in whom an ileostomy was raised and later closed during a 5
      year period formed the study group. When colorectal cancer surveillance computed
      tomography (CT) was undertaken the images were scrutinized and graded as to
      defined anatomical abnormalities. RESULTS: One hundred and seventy-nine patients
      had an ileostomy, of which 92 were diverting. Fifty-nine (64%) were closed at
      various intervals (median time to closure 6 (2-22) months and 43 underwent a
      surveillance CT at 1-3 (median 2) years. At 1 year an abnormality (atrophy or
      defect) at the site of closure was seen in 16 (37%) CT scans. These were more
      frequent with increasing duration of follow-up. One asymptomatic hernia was
      detected at 2 years but there was no deterioration in the abdominal wall at 3
      years when compared with that at 2 years. CONCLUSION: Abnormalities in the
      abdominal wall at the site of a closed diverting ileostomy are common but true
      herniation is unusual. The routine use of prophylactic mesh at ileostomy closure
      may be unnecessary.

PMID- 22471313
TI  - Intrinsically photosensitive retinal ganglion cell function in relation to age: a
      pupillometric study in humans with special reference to the age-related optic
      properties of the lens.
AB  - BACKGROUND: The activity of melanopsin containing intrinsically photosensitive
      ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to
      bright blue (appr.480 nm) light. Due to age related factors in the eye,
      particularly, structural changes of the lens, less light reaches retina. The aim
      of this study was to examine how age and in vivo measured lens transmission of
      blue light might affect pupil light responses, in particular, mediated by the
      ipRGC. METHODS: Consensual pupil responses were explored in 44 healthy subjects
      aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s
      light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9
      and 14.8 log photons/cm2/s, respectively). Additional recordings were performed
      using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline
      pupil size was measured in darkness and results were adjusted for the baseline
      pupil and gender. The main outcome parameters were maximal and sustained pupil
      contraction amplitudes and the postillumination response assessed as area under
      the curve (AUC) over two time-windows: early (0-10 s after light termination) and
      late (10-30 s after light termination). Lens transmission was measured with an
      ocular fluorometer. RESULTS: The sustained pupil contraction and the early
      poststimulus AUC correlated positively with age (p=0.02, p=0.0014, respectively)
      for the blue light stimulus condition only.The maximal pupil contraction
      amplitude did not correlate to age either for bright blue or red light stimulus
      conditions.Lens transmission decreased linearly with age (p<0.0001). The pupil
      response was stable or increased with decreasing transmission, though only
      significantly for the early poststimulus AUC to 300 cd/m2 light (p=0.02).
      CONCLUSIONS: Age did not reduce, but rather enhance pupil responses mediated by
      ipRGC. The age related decrease of blue light transmission led to similar
      results, however, the effect of age was greater on these pupil responses than
      that of the lens transmission. Thus there must be other age related factors such
      as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil
      response enhancement observed with advancing age.

PMID- 22471314
TI  - The aging Canadian population and hospitalizations for acute myocardial
      infarction: projection to 2020.
AB  - BACKGROUND: The risk of experiencing an acute myocardial infarction (AMI)
      increases with age and Canada's population is aging. The objective of this
      analysis was to examine trends in the AMI hospitalization rate in Canada between
      2002 and 2009 and to estimate the potential increase in the number of AMI
      hospitalizations over the next decade. METHODS: Aggregated data on annual AMI
      hospitalizations were obtained from the Canadian Institute for Health Information
      for all provinces and territories, except Quebec, for 2002/03 and 2009/10. Using
      these data in a Poisson regression model to control for age, gender and year, the
      rate of AMI hospitalizations was extrapolated between 2010 and 2020. The
      extrapolated rate and Statistics Canada population projections were used to
      estimate the number of AMI hospitalizations in 2020. RESULTS: The rates of AMI
      hospitalizations by gender and age group showed a decrease between 2002 and 2009
      in patients aged >= 65 years and relatively stable rates in those aged < 64 years
      in both males and females. However, the total number of AMI hospitalizations in
      Canada (excluding Quebec) is projected to increase by 4667 from 51847 in 2009 to
      56514 in 2020, a 9.0% increase. Inflating this number to account for the
      unavailable Quebec data results in an increase of approximately 6200 for the
      whole of Canada. This would amount to an additional cost of between $46 and $54
      million and sensitivity analyses indicate that it could be between $36 and $65
      million. CONCLUSIONS: Despite projected decreasing or stable rates of AMI
      hospitalization, the number of hospitalizations is expected to increase
      substantially as a result of the aging of the Canadian population. The cost of
      these hospitalizations will be substantial. An increase of this extent in the
      number of AMI hospitalizations and the ensuing costs would significantly impact
      the already over-stretched Canadian healthcare system.

PMID- 22471315
TI  - Structure of a peptide adsorbed on graphene and graphite.
AB  - Noncovalent functionalization of graphene using peptides is a promising method
      for producing novel sensors with high sensitivity and selectivity. Here we
      perform atomic force microscopy, Raman spectroscopy, infrared spectroscopy, and
      molecular dynamics simulations to investigate peptide-binding behavior to
      graphene and graphite. We studied a dodecamer peptide identified with phage
      display to possess affinity for graphite. Optical spectroscopy reveals that the
      peptide forms secondary structures both in powder form and in an aqueous medium.
      The dominant structure in the powder form is alpha-helix, which undergoes a
      transition to a distorted helical structure in aqueous solution. The peptide
      forms a complex reticular structure upon adsorption on graphene and graphite,
      having a helical conformation different from alpha-helix due to its interaction
      with the surface. Our observation is consistent with our molecular dynamics
      calculations, and our study paves the way for rational functionalization of
      graphene using biomolecules with defined structures and, therefore,
      functionalities.

PMID- 22471316
TI  - Can functionalized cucurbituril bind actinyl cations efficiently? A density
      functional theory based investigation.
AB  - The feasibility of using cucurbituril host molecule as a probable actinyl cation
      binders candidate is investigated through density functional theory based
      calculations. Various possible binding sites of the cucurbit[5]uril host molecule
      to uranyl are analyzed and based on the binding energy evaluations, MU(5)-binding
      is predicted to be favored. For this coordination, the structure, vibrational
      spectra, and binding energies are evaluated for the binding of three actinyls in
      hexa-valent and penta-valent oxidation states with functionalized cucurbiturils.
      Functionalizing cucurbituril with methyl and cyclohexyl groups increases the
      binding affinities of actinyls, whereas fluorination decreases the binding
      affinities as compared to the native host molecule. Surprisingly hydroxylation of
      the host molecule does not distinguish the oxidation state of the three actinyls.

PMID- 22471318
TI  - Sheep laterality.
AB  - Turning preferences among 309 white-faced ewes were individually evaluated in an
      enclosed, artificially lit T-maze, followed by each ewe choosing either a right
      or left return alley to return to peers. Data recorded included time in the start
      box, time in the T-maze, exit arm chosen to leave the T-maze, and return alley.
      Right and left arms of the T-maze were chosen 65.7% and 34.3% of the time,
      respectively, while right and left return alleys were chosen 32.4% and 67.6%,
      respectively. Exit arm and return alley were not independently chosen (p <.0001),
      with observed counts being higher than expected under independence when ewes made
      the same choice for exit and alley (RR or LL turn patterns) and being lower than
      expected for alternating choices (RL or LR). Out of the 309 ewes, 28.2% and 30.1%
      chose RR and LL turn patterns, respectively, while 37.5% chose the RL turn
      pattern, but only 13 (4.2%) chose the LR turning pattern. Overall, ewes that
      initially turned right when presented a second turning opportunity had a slight
      preference to alternate their turning direction, while ewes that initially turned
      left tended to continue turning left when given another chance to turn. Exit arm
      and return alley laterality was not related (alpha =.05) to time of day the test
      was administered, ewe's age or genetics, most recent liveweight, or most recent
      shorn fleece weight. The mean time spent in the start box (21 s) was not related
      to exit arm (p =.947) or return alley (p =.779). Mean time (15 s) spent in the T
      maze was not related to exit arm (p =.086) or return alley (p =.952). More
      research will be required to understand sheep turning laterality and how it can
      impact working facilities and research equipment.

PMID- 22471317
TI  - Comparison of (64)Cu-complexing bifunctional chelators for
      radioimmunoconjugation: labeling efficiency, specific activity, and in vitro/in
      vivo stability.
AB  - High radiolabeling efficiency, preferably to high specific activity, and good
      stability of the radioimmunoconjugate are essential features for a successful
      immunoconjugate for imaging or therapy. In this study, the radiolabeling
      efficiency, in vitro stability, and biodistribution of immunoconjugates with
      eight different bifunctional chelators labeled with (64)Cu were compared. The
      anti-CD20 antibody, rituximab, was conjugated to four macrocyclic bifunctional
      chelators (p-SCN-Bn-DOTA, p-SCN-Bn-Oxo-DO3A, p-SCN-NOTA, and p-SCN-PCTA), three
      DTPA derivatives (p-SCN-Bn-DTPA, p-SCN-CHX-A"-DTPA, and ITC-2B3M-DTPA), and a
      macrobicyclic hexamine (sarcophagine) chelator (sar-CO2H) = (1-NH2-8
      NHCO(CH2)3CO2H)sar where sar = sarcophagine = 3,6,10,13,16,19
      hexaazabicyclo[6.6.6]icosane). Radiolabeling efficiency under various conditions,
      in vitro stability in serum at 37  degrees C, and in vivo biodistribution and
      imaging in normal mice over 48 h were studied. All chelators except sar-CO2H were
      conjugated to rituximab by thiourea bond formation with an average of 4.9 +/- 0.9
      chelators per antibody molecule. Sar-CO2H was conjugated to rituximab by amide
      bond formation with 0.5 chelators per antibody molecule. Efficiencies of (64)Cu
      radiolabeling were dependent on the concentration of immunoconjugate. Notably,
      the (64)Cu-NOTA-rituximab conjugate demonstrated the highest radiochemical yield
      (95%) under very dilute conditions (31 nM NOTA-rituximab conjugate). Similarly,
      sar-CO-rituximab, containing 1/10th the number of chelators per antibody compared
      to that of other conjugates, retained high labeling efficiency (98%) at an
      antibody concentration of 250 nM. In contrast to the radioimmunoconjugates
      containing DTPA derivatives, which demonstrated poor serum stability, all
      macrocyclic radioimmunoconjugates were very stable in serum with <6% dissociation
      of (64)Cu over 48 h. In vivo biodistribution profiles in normal female Balb/C
      mice were similar for all the macrocyclic radioimmunoconjugates with most of the
      activity remaining in the blood pool up to 48 h. While all the macrocyclic
      bifunctional chelators are suitable for molecular imaging using (64)Cu-labeled
      antibody conjugates, NOTA and sar-CO2H show significant advantages over the
      others in that they can be radiolabeled rapidly at room temperature, under dilute
      conditions, resulting in high specific activity. 

PMID- 22471319
TI  - Social skills as a mediator between anxiety symptoms and peer interactions among
      children and adolescents.
AB  - The present study used a cross-sectional design to examine the relations among
      youth anxiety symptoms, positive and negative peer interactions, and social
      skills. Also examined was the mediating role of social skills in the relations
      between youth anxiety symptoms and positive and negative peer interactions. Youth
      sex and age were examined as moderators. The sample consisted of 397 children and
      adolescents (M = 10.11 years; 53.4% boys; 74.8% Hispanic Latino) referred to an
      anxiety disorders clinic. Anxiety symptoms, positive and negative peer
      interactions, and social skills were assessed using youth and parent ratings.
      Structural equation modeling results indicated that for youth ratings only, youth
      anxiety symptoms were negatively related to positive peer interactions
      controlling for primary social phobia and comorbid depressive disorders. For both
      youth and parent ratings, youth anxiety symptoms were positively related to
      negative peer interactions and negatively related to social skills. Also for both
      youth and parent ratings, social skills mediated the relations between youth
      anxiety symptoms and positive and negative peer interactions. For parent ratings
      only, the effects of youth anxiety symptoms and social skills on peer
      interactions were significantly moderated by youth age. Youth sex was not a
      significant moderator using youth and parent ratings. Findings suggest that
      difficulties with social skills and peer interactions are problematic features of
      youth referred for anxiety problems. Findings highlight the need to improve
      understanding of anxiety symptoms, social skills, and peer interactions in this
      population.

PMID- 22471322
TI  - Challenges of biomarkers in drug discovery and development.
AB  - Biomarker data are essential in the discovery and development of new drugs.
      However, pathways needed to make sure that biomarker data are accepted by
      regulatory agencies may be considered an unnecessary burden on the critical path
      for drug development. There is the need to consider early in discovery and
      development that these pathways for biomarker acceptance or qualification not
      only are necessary, but may also enhance the success of novel therapies through
      regulatory review and clinical use. There also needs to be a focus on the
      challenge in the application of biomarkers as these approach regulatory
      evaluation. Regulatory guidance is needed on how a patient population may be
      defined by the molecular phenotype classification associated with specific
      mutations in patient genomes. Enzyme replacement therapies have been implicitly
      approved in the past assuming a molecular phenotype of a defective enzyme, but
      these and other precedents have not yet been translated into regulatory guidance.
      A second regulatory pathway for biomarkers is a biomarker qualification process.
      Biomarker data may be submitted, in the context of a specific NDA, but the
      biomarker qualification process has added a path through which efficacy and
      safety biomarkers useful in product development across multiple companies may be
      qualified through pre-competitive collaboration between these companies.

PMID- 22471323
TI  - Ligand aligning method for molecular docking: alignment of property-weighted
      vectors.
AB  - To reduce searching effort in conformational space of ligand docking positions,
      we propose an algorithm that generates initial binding positions of the ligand in
      a target protein, based on the property-weighted vector (P-weiV), the three
      dimensional orthogonal vector determined by the molecular property of hydration
      free energy density. The alignment of individual P-weiVs calculated separately
      for the ligand and the protein gives the initial orientation of a given ligand
      conformation relative to an active site; these initial orientations are then
      ranked by simple energy functions, including solvation. Because we are using
      three-dimensional orthogonal vectors to be aligned, only four orientations of
      ligand positions are possible for each ligand conformation, which reduces the
      search space dramatically. We found that the performance of P-weiV compared
      favorably to the use of principle moment of inertia (PMI) as implemented in
      LigandFit when we tested the abilities of the two approaches to correctly predict
      205 protein-ligand complex data sets from the PDBBind database. P-weiV correctly
      predicted the alignment of ligands (within rmsd of 2.5 A) with 57.6% reliability
      (118/205) for the top 10 ranked conformations and with 74.1% reliability
      (152/205) for the top 50 ranked conformations of Catalyst-generated conformers,
      as compared to 22.9% (47/205) and 31.2% (64/205), respectively, in the case of
      PMI with the same conformer set.

PMID- 22471324
TI  - Elevated levels of salivary lactoferrin, a marker for chronic periodontitis?
AB  - BACKGROUND AND OBJECTIVE: Whole saliva is a complex mixture of fluids essential
      for the well-being of the oral hard and soft tissues. Saliva contains numerous
      antimicrobial proteins that help protect the oral ecosystem from infectious
      agents. Chronic periodontitis is an infectious chronic inflammatory condition
      that affects the tooth-supporting structures and leads to their destruction. The
      aim of the present study was to investigate differences in concentrations of
      salivary lactoferrin in subjects with and without periodontal disease and
      correlate these values with clinical variables associated with periodontal
      disease. MATERIAL AND METHODS: Stimulated whole saliva was collected from 17
      subjects with chronic periodontitis and 17 periodontally healthy control
      subjects. Data relating to bleeding on probing, probing pocket depth and
      horizontal bone loss were registered. Concentrations of lactoferrin, lysozyme and
      IgA in stimulated whole saliva were quantified using ELISA. RESULTS: Subjects
      with chronic periodontits showed higher concentrations of lactoferrin in
      stimulated whole saliva compared with periodontally healthy control subjects (p <
      0.05). Salivary concentrations of lactoferrin were positively correlated with
      bleeding on probing (p < 0.001) and the number of sites with probing pocket depth
      >= 6 mm (p < 0.001). CONCLUSION: Lactoferrin is raised in stimulated whole saliva
      in subjects with chronic periodontitis and is correlated with probing pocket
      depth >= 6 mm.

PMID- 22471325
TI  - 'We just stick together': how disabled teens negotiate stigma to create lasting
      friendship.
AB  - BACKGROUND: Friendship is a crucial relationship offering practical support,
      enjoyment and improved health. When disability is added into the mix, the
      permutations of friendship shift. Despite the presence of inclusive social
      policies many disabled teens continue to experience stigma and social isolation,
      yet some teens are able to establish long-term friendships. METHODS: A nuanced
      understanding about how disabled teens navigate stigma to create lasting
      friendships was constructed through this qualitative study. Seven boys and seven
      girls between the ages 15 to 20 years who experienced disability engaged in
      research interviews and participant observation sessions. Nine adults were also
      interviewed. A critical approach to data analysis was complimented by coding in
      Atlas.ti. RESULTS: This article describes the strategies used by these disabled
      teens to make and keep friends: disrupting norms about friendship, coming out as
      disabled, connecting through stigma and choosing self-exclusion. CONCLUSION:
      Disabled teens in this study felt a greater sense of belonging when with peers
      who shared the disability experience, thus self-exclusion was a viable strategy
      for creating sustainable friendships in the context of oppression. Social policy
      informed by the experiences of disabled youth in the current study will more
      effectively promote social inclusion by first acknowledging and then disrupting
      ableism.

PMID- 22471326
TI  - Spectrum of pediatric dermatological emergencies at a tertiary care hospital in
      India: a descriptive study.
AB  - BACKGROUND: Dermatological emergencies in children are not uncommon. Worldwide,
      limited studies have been done to study the spectrum of such emergencies. The aim
      of our study was to analyze the spectrum of dermatological emergencies in the
      pediatric age group. MATERIALS AND METHODS: Over a period of 18 months, ninety
      consecutive patients under 18 years of age presenting with cutaneous in addition
      to emergency disorders as assessed by the Nelson's severity scoring system were
      recruited. RESULTS: The most common emergency was primary cutaneous infections
      (40%), followed by adverse cutaneous drug reactions (13.33%). Staphylococcal
      scalded skin syndrome was the most frequent infection, and the most common
      adverse cutaneous drug reaction was Stevens-Johnson syndrome and toxic epidermal
      necrolysis. Other emergencies included purpura fulminans (12.22%), congenital
      dermatoses (11.11%), vasculitis (8.90%), angioedema (6.67%), collagen vascular
      diseases (2.22%), serum sickness (2.22%), post-varicella cerebellitis (1.11%),
      post-infected scabies glomerulonephritis (1.11%), and Langerhans cell
      histiocytosis (1.11%). These emergencies presented in equal numbers to the
      outpatient department of dermatology or pediatrics and to the emergency
      department. CONCLUSION: Our study recommends the use of standard scoring systems
      such as the Nelson's score to assess sick children. The appropriateness of this
      scale or other scales for the assessment of dermatological emergencies needs to
      be established. Over half of our cases were initially assessed by pediatricians
      and emergency personnel, highlighting the importance of spreading awareness about
      cutaneous emergencies and providing them with access to a dermatologist's
      services.

PMID- 22471327
TI  - Developing and testing a strategy to enhance a palliative approach and care
      continuity for people who have dementia: study overview and protocol.
AB  - BACKGROUND: Typically, dementia involves progressive cognitive and functional
      deterioration, leading to death. A palliative approach recognizes the inevitable
      health decline, focusing on quality of life. The approach is holistic, proactive,
      supports the client and the family, and can be provided by the client's usual
      care team.In the last months of life, distressing symptoms, support needs, and
      care transitions may escalate. This project trialed a strategy intended to
      support a consistent, high quality, palliative approach for people with dementia
      drawing close to death. The strategy was to implement two communities of
      practice, drawn primarily from service provider organizations across care
      sectors, supporting them to address practice change. Communities comprised
      practitioners and other health professionals with a passionate commitment to
      dementia palliative care and the capacity to drive practice enhancement within
      partnering organizations.Project aims were to document: (i) changes driven by the
      communities of practice; (ii) changes in staff/practitioner characteristics
      during the study (knowledge of a palliative approach and dementia; confidence
      delivering palliative care; views on death and dying, palliative care, and a
      palliative approach for dementia); (iii) outcomes from perspectives of family
      carers, care providers, and community of practice members; (iv) the extent to
      which changes enhanced practice and care continuity; and (v) barriers to and
      facilitators of successful community of practice implementation. METHODS/DESIGN:
      This action research project was implemented over 14 months in 2010/11 in
      metropolitan Perth, Western Australia and regional Launceston, Tasmania. Each
      state based community of practice worked with the researchers to scope existing
      practice and its outcomes. The research team compiled a report of existing
      practice recommendations and resources. Findings of these two steps informed
      community of practice action plans and development of additional resources.
      Change implementation was recorded and explored in interviews, comparisons being
      made with practice recommendations. Changes in staff/practitioner characteristics
      were evaluated using survey data. Findings from semi structured interviews and
      survey administration established outcomes from perspectives of family carers,
      care providers, and community of practice members. Consideration of processes and
      outcomes, across the two state based settings, informed identification of
      barriers and facilitators. Community of practice reflections also informed study
      recommendations.

PMID- 22471328
TI  - Prepubertal follow-up after hypospadias repair with autologous in vitro cultured
      urothelial cells.
AB  - AIM: To evaluate the long-term effects on hypospadias repair with cultured
      autologous urothelial cells. METHODS: From 2000 to 2002, six patients with
      scrotal or perineal hypospadias and pronounced chordee were treated surgically
      with cultured autologous urothelial cell transplants. All patients were evaluated
      at 6-8 years postoperatively, that is, in the prepubertal period. The outcome was
      assessed with respect to cosmetic appearance, voiding function, urinary flow,
      artificial erection, urethroscopy and biopsies. RESULTS: Median follow-up time
      was 7.25 years. Up to date, all patients present with a good cosmetic appearance.
      One of the boys prefers a sitting voiding position. Urinary flow curves are bell
      shaped in all but one. All have straight erections, urethroscopy reveals an even,
      non-hair-bearing surface on the transplanted side and 2/6 present with urothelial
      cells in biopsies. Limitations of this follow-up study include a small group of
      patients and lack of controls. However, patients with severe hypospadias have
      high complication rates, and our results are equal or better than expected for
      the phenotype. CONCLUSION: Tissue engineering for severe hypospadias repair can
      be performed in a safe manner. The method is feasible for treatment of a selected
      group of hypospadias, where pronounced chordee and shortage of preputial and
      penile skin complicates the creation of a neourethra.

PMID- 22471329
TI  - Hermeneutic single-case efficacy design.
AB  - In this article, I outline hermeneutic single-case efficacy design (HSCED), an
      interpretive approach to evaluating treatment causality in single therapy cases.
      This approach uses a mixture of quantitative and qualitative methods to create a
      network of evidence that first identifies direct demonstrations of causal links
      between therapy process and outcome and then evaluates plausible nontherapy
      explanations for apparent change in therapy. I illustrate the method with data
      from a depressed client who presented with unresolved loss and anger issues.

PMID- 22471330
TI  - Relationships among Therapist Presession Mood, Therapist Empathy, and Session
      Evaluation.
AB  - Intellectual empathy, operationalized as the counselor's accuracy in perceiving a
      client's emotions, and empathic emotion, or the similarity between the
      therapist's and the client's emotions, were examined in relation to therapist
      presession mood and clients' session evaluations. Fifty-eight client-therapist
      dyads completed the Multiple Affect Adjective Check List (Zuckerman, Lubin, &
      Rinck, 1983) before and after a midtreatment counseling session. Clients also
      completed the Session Evaluation Questionnaire (Stiles & Snow, 1984). Results
      showed that both intellectual empathy and empathic emotion contributed
      significantly to client-rated session depth but not session smoothness. Counselor
      presession positive affect was negatively related to empathic emotion, whereas
      counselor presession anxiety was positively related to intellectual empathy.

PMID- 22471331
TI  - TIME MATTERS: On Temporal Interactions in Long-term follow-up of Long-term
      Psychotherapies.
AB  - The roles of treatment duration, session frequency, and their interaction ~ere
      studied in a. sample of 156 patients who had terminated psychotherapy. or
      psychoanalysis. The outcome parameters were treatment end-state and posttreatment
      change with respect to symptom distress, measured by the General Symptom Index
      from the Symptom Checklist-90 (SCL-90); morale, as indicated by the Sense of
      Coherence Scale (SOCS) overall mean; and the quality of social functioning,
      according to the Social Adjustment Scale overall mean1 all of them taken for 3
      consecutive years after termination of treatment. Growth curve modeling on the
      basis of covariance and mean structures yielded 5 principal results. First,
      outcome changed significantly after treatment termination. Second, end-state and
      posttreatment changes were influenced by duration and frequency but primarily in
      interaction. Thus, the effects of duration and frequency were conditional on each
      other. Third, the joint effects on end-state were ,small and on posttreatment
      change, small to moderate. Fourth, on the. SCL-90 and the SOCS, there were
      outcome reversals during the posttreatment period such that good end-states
      deteriorated in the long run, whereas modest end-states improved considerably.
      Fifth, generally, the findings seemed to favor lowduration/ low-frequency and
      high-duration/high-frequency treatments in this sample.

PMID- 22471332
TI  - FRAMES: The Method in Action and the Assessment of Its Reliability.
AB  - This article reintroduces an alternative method of thematic structure and content
      analysis called FRAMES (Fundamental, Repetitive, and Maladaptive Emotion
      Structures). Although this measure has been generally received as clinically
      sensitive and compelling, it has not been widely used by psychotherapy
      researchers, presumably because of methodological concerns and logistical
      complexity. First, we present a brief overview of FRAMES for the unfamiliar
      reader, including the methodological refinements that have been made. This new
      method for finding FRAMES is demonstrated for the first time with segments of
      verbatim psychotherapy transcripts. A set of methods for assessing the interrater
      reliability of this method is then introduced. The results of the first study of
      the reliability of FRAMES in a psychotherapy case are then presented. This study
      is a precursor to future articles that present the results of the first
      longitudinal study of FRAMES in this same case.

PMID- 22471333
TI  - BERN INVENTORY OF TREATMENT GOALS: PART 1. Development and First Application of a
      Taxonomy of Treatment Goal Themes.
AB  - The taxonomy of treatment goal themes of the Bern Inventory of Treatment Goals
      (BIT-T) is presented. The taxonomy was developed using 1,031 treatment goals of
      298 outpatients at a university clinic. A first version of the taxonomy was
      constructed by cluster-analyzing eo-occurrence values computed from
      categorizations made by 22 therapists. Iterative revisions after several rating
      trials resulted in BIT-T Version 3.1. Categories at the highest of three levels
      of abstraction are coping with specific problems and symptoms (P), interpersonal
      goals (I), well-being and functioning (W), existential issues (E), and personal
      growth (G). In (re-)coding an extended sample of outpatient treatment goals, the
      BIT-T proved to have a good interrater reliability, identified differences
      between diagnostic groups, and showed meaningful relations to standardized intake
      measures. Applications of the taxonomy for research and practice purposes as well
      as possible consequences of the obtained first results are discussed.

PMID- 22471335
TI  - Epithelial tumours of the lacrimal gland: a clinical, histopathological, surgical
      and oncological survey.
AB  - Epithelial tumours of the lacrimal gland represent a large spectrum of lesions
      with similarities in clinical signs and symptoms but with different biological
      behaviour and prognosis. They are rare, but with aggressive malignant potential.
      Tumours of the lacrimal gland may present with swelling of the lacrimal gland,
      displacement of the eyeball, reduced eye motility and diplopia. Pain and symptoms
      of short duration before the first ophthalmic consultation are characteristic of
      malignant tumours. The histological diagnosis determines the subsequent treatment
      regimen and provides important clues regarding the prognosis. The purpose of this
      paper is to describe the various primary epithelial tumours of the lacrimal
      gland. In the first part of the review, the frequency, demographics, clinical
      presentation and diagnostic features are described. In the second part, primarily
      tumour-specific histological characteristics are given. Finally, treatment
      modalities including surgical procedures and medical oncology as well as
      prognosis are discussed.

PMID- 22471337
TI  - Diffusion of contrast medium after four different techniques for analgesia of the
      proximal metacarpal region: an in vivo and in vitro study.
AB  - REASONS FOR PERFORMING STUDY: There is limited information on potential diffusion
      of local anaesthetic solution after various diagnostic analgesic techniques of
      the proximal metacarpal region. OBJECTIVE: To document potential distribution of
      local anaesthetic solution following 4 techniques used for diagnostic analgesia
      of the proximal metacarpal region. METHODS: Radiodense contrast medium was
      injected around the lateral palmar or medial and lateral palmar metacarpal nerves
      in 8 mature horses, using 4 different techniques. Radiographs were obtained 0, 10
      and 20 min after injection and were analysed subjectively. A mixture of
      radiodense contrast medium and methylene blue was injected into 4 cadaver limbs;
      the location of the contrast medium and dye was determined by radiography and
      dissection. RESULTS: Following perineural injection of the palmar metacarpal
      nerves, most of the contrast medium was distributed in an elongated pattern axial
      to the second and fourth metacarpal bones. The carpometacarpal joint was
      inadvertently penetrated in 4/8 limbs after injections of the palmar metacarpal
      nerves from medial and lateral approaches, and in 1/8 limbs when both injections
      were performed from the lateral approach. Following perineural injection of the
      lateral palmar nerve using a lateral approach, the contrast medium was diffusely
      distributed in all but one limb, in which the carpal sheath was inadvertently
      penetrated. In 5/8 limbs, following perineural injection of the lateral palmar
      nerve using a medial approach, the contrast medium diffused proximally to the
      distal third of the antebrachium. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Inadvertent penetration of the carpometacarpal joint is common after perineural
      injection of the palmar metacarpal nerves, but less so if both palmar metacarpal
      nerves are injected using a lateral approach. Following injection of the lateral
      palmar nerve using a medial approach, the entire palmar aspect of the carpus may
      be desensitised.

PMID- 22471336
TI  - Detection of KCNJ11 gene mutations in a family with neonatal diabetes mellitus:
      implications for therapeutic management of family members with long-standing
      disease.
AB  - BACKGROUND: Activating mutations of potassium inwardly-rectifying channel,
      subfamily J, member 11 (KCNJ11), which encodes Kir6.2 (beta-cell adenosine
      triphosphate-sensitive potassium [K(ATP)] channel subunit), have been associated
      with neonatal diabetes mellitus (NDM) in different studies. Treatment with oral
      sulfonylureas in place of exogenous insulin injections results in improved
      glycemic control in most patients carrying these mutations. Exploration of
      genetic causes of NDM occurring before the age of 6 months has been proposed as
      an important issue in identification of monogenic forms of diabetes, which might
      be critical in their therapeutic management, as a consequence. METHODS: Mutation
      screening of the KCNJ11 gene was carried out using PCR amplification followed by
      direct sequencing in three family members: the proband, ND1, diagnosed at 40 days
      of age (current age 7 years); his sibling, ND2, diagnosed at 2 years of age
      (current age 14 years); and their father, ND3, diagnosed at 15 years of age
      (current age 35 years), who had been exclusively treated with insulin. The effect
      of the E227K mutation was also examined in a homology model of Kir6.2. RESULTS:
      Our results revealed the presence of the heterozygous missense mutation c. 679
      G/A (E227K) in all three patients, who were all able to successfully transfer
      from insulin injections to an oral sulfonylurea, with improved glycemic control.
      CONCLUSION: We found that three members of a family with highly variable age of
      onset of insulin-treated diabetes, diagnosed at 40 days, 2 years, and 15 years of
      age, all carried the E227K mutation in KCNJ11 and could switch to an oral
      sulfonylurea. This mutation has been previously reported in patients with
      permanent and transient NDM, as well as later-onset diabetes; this report adds to
      the variability in phenotypic presentation and further supports genetic testing
      in all diabetic members of any family affected by NDM.

PMID- 22471338
TI  - Environmental enrichment improves behavioral outcome in the AY-9944 model of
      childhood atypical absence epilepsy.
AB  - Atypical absence seizures are drug resistant in the majority of children with
      Lennox-Gastaut syndrome and herald a poor neurodevelopmental outcome. Here we
      studied the effects of environmental enrichment, enriched housing conditions
      designed to stimulate sensory and motor systems in the brain, on behavioral
      outcome in mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY),
      a clinically relevant model of atypical absence epilepsy. Beginning at postnatal
      day (P) 2, C3H mice were treated with AY (7.5 mg/kg) every 6 days until P20 and
      then weaned into enriched or standard cages. After 30 days (~P50), AY mice from
      the enriched housing condition exhibited less behavioral hyperactivity and
      anxiety, improved olfactory recognition, and spatial learning, but no significant
      reduction in the number of ictal discharges in comparison with their non-enriched
      cohorts. The beneficial effects of environmental enrichment in AY model were in
      some behavioral tests gender-specific in favor of males suggesting that other,
      possibly hormonally mediated mechanisms, may interact with the therapeutic
      effects of enrichment. Taken together, these data provide a starting point to
      derive clinical occupational therapies for improving behavioral outcome in cases
      of intractable childhood seizures.

PMID- 22471340
TI  - Split myomucosal advancement flap for reconstruction of a lower lip defect.

PMID- 22471339
TI  - Prevalence and correlates of insomnia in a polish sample of alcohol-dependent
      patients.
AB  - BACKGROUND: Insomnia is an important symptom in alcohol-dependent patients
      because it may persist despite abstinence and predispose to relapse to drinking.
      The goal of the present study was to evaluate the prevalence and clinical
      correlates of insomnia in a sample of 302 alcohol-dependent patients admitted to
      treatment programs in Poland. METHODS: Participants were mostly men (73.8%) with
      a mean (SD) age of 43.5 (9.7) years. Insomnia in the past 1 month was assessed
      using a total score of 6 or higher on the Athens Insomnia Scale. RESULTS:
      Insomnia affected 62.9% of patients, and delayed sleep induction was the most
      common subtype. Insomnia was associated in bivariate analyses with less
      education, inadequate finances, problem drinking at an earlier age of onset,
      drinking frequency and quantity, drinking-related consequences, severity of
      alcohol and nicotine dependence, psychiatric and physical severity, and a
      childhood history of sexual or physical abuse (p < 0.05). Logistic regression
      analysis showed that mental and physical health status, severity of alcohol
      dependence, number of drinking days in the past 3 months, and childhood abuse
      were independent predictors of insomnia, explaining approximately 30 to 40% of
      the variance. CONCLUSIONS: More than 60% of alcohol-dependent patients in a
      Polish sample screened positive for insomnia using a validated scale, a rate
      similar to those assessed with other scales in other countries. The study also
      showed that insomnia in alcohol-dependent patients is associated with poor
      physical health and childhood abuse, similar to the general population. The
      multifactorial nature of insomnia in alcohol-dependent patients has treatment
      implications.

PMID- 22471342
TI  - Ultrafast dynamics of metal complexes of tetrasulphonated phthalocyanines.
AB  - A promising material in medicine, electronics, optoelectronics, electrochemistry,
      catalysis, and photophysics, tetrasulphonated aluminum phthalocyanine (AlPcS(4)),
      is investigated by means of steady-state and time-resolved pump-probe
      spectroscopies. Absorption and steady-state fluorescence spectroscopy indicate
      that AlPcS(4) is essentially monomeric. Spectrally resolved pump-probe data are
      recorded on time scales ranging from femtoseconds to nanoseconds. The nature of
      these fast processes and pathways of the competing relaxation processes from the
      initially excited electronic states in aqueous and organic (dimethyl sulfoxide)
      solutions are discussed. The decays and bleaching recovery have been fitted in
      the ultrafast window (0-10 ps) and later time window extending to nanoseconds (0
      1 ns). While the excited-state dynamics have been found to be sensitive to the
      solvent environment, we were able to show that the fast dynamics is described by
      three time constants in the ranges of 115-500 fs, 2-25 ps, and 150-500 ps. We
      were able to ascribe these three time constants to different processes. The
      shortest time constants have been assigned to vibrational wavepacket dynamics.
      The few picosecond components have been assigned to vibrational relaxation in the
      excited electronic states. Finally, the 150-500 ps components represent the decay
      from S(1) to the ground state. The experimental and theoretical treatment
      proposed in this paper provides a basis for a substantial revision of the
      commonly accepted interpretation of the Soret transition (B transition) that
      exists in the literature.

PMID- 22471344
TI  - Current perspectives to overcome a positive crossmatch in living donor renal
      transplantation.

PMID- 22471341
TI  - Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and
      multicenter cohort study.
AB  - Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant
      recipients were included in a prospective multicenter study. Thirty-six (43%)
      HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival
      rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008),
      respectively. When both groups were considered together, HIV infection was an
      independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]).
      Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV
      genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI,
      2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be
      associated with mortality. When this analysis was restricted to pretransplant
      variables, we identified three independent factors (HCV genotype 1, pretransplant
      MELD score and centers with <1 liver transplantation/year in HIV-infected
      patients) that allowed us to identify a subset of 60 (71%) patients with a
      similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected
      recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients
      was lower than in HCV-monoinfected recipients, although an important subset with
      a favorable prognosis was identified in the former.

PMID- 22471343
TI  - Validation of activity questionnaires in patients with cystic fibrosis by
      accelerometry and cycle ergometry.
AB  - BACKGROUND: The objective of this study was to validate physical activity
      questionnaires for cystic fibrosis (CF) against accelerometry and cycle
      ergometry. METHODS: 41 patients with CF (12-42 years) completed the Habitual
      Activity Estimation Scale (HAES), the 7-Day Physical Activity Recall
      questionnaire (7D-PAR) and the Lipid Research Clinics questionnaire (LRC) and
      performed an incremental exercise test according to the Godfrey protocol up to
      volitional fatigue. Time spent in moderate and vigorous physical activity (MVPA)
      assessed objectively by accelerometry was related to the time spent in the
      respective activity categories by correlation analyses and calculating intraclass
      correlation coefficients (ICC). Furthermore, the results of the exercise test
      were correlated with the results of the questionnaires. RESULTS: Time spent in
      the categories 'hard','very hard' and 'hard & very hard' of the 7D-PAR (0.41 < r
      < 0.56) and 'active' (r = 0.33) of the HAES correlated significantly with MVPA.
      The activity levels of the LRC were not related to objectively determined
      physical activity. Significant ICCs were only observed between the 7D-PAR
      activitiy categories and MVPA (ICC = 0.40-0.44). Only the LRC showed moderate
      correlations with the exercise test (Wmax: r = 0.46, p = 0.002; VO2peak: r =
      0.32, p = 0.041). CONCLUSIONS: In conclusion, the activity categories 'hard' and
      'very hard' of the 7D-PAR best reflected objectively measured MVPA. Since the
      association was at most moderate, the 7D-PAR may be selected to describe physical
      activity within a population. None of the evaluated questionnaires was able to
      generate valid physical activity data exercise performance data at the individual
      level. Neither did any of the questionnaires provide a valid assessment of
      aerobic fitness on an invidual level.

PMID- 22471345
TI  - Everolimus plus early tacrolimus minimization: a phase III, randomized, open
      label, multicentre trial in renal transplantation.
AB  - There is increasing interest in tacrolimus-minimization regimens. ASSET was an
      open-label, randomized, 12-month study of everolimus plus tacrolimus in de-novo
      renal-transplant recipients. Everolimus trough targets were 3-8 ng/ml throughout
      the study. Tacrolimus trough targets were 4-7 ng/ml during the first 3 months and
      1.5-3 ng/ml (n = 107) or 4-7 ng/ml (n = 117) from Month 4. All patients received
      basiliximab induction and corticosteroids. The primary objective was to
      demonstrate superior estimated glomerular filtration rate (eGFR; MDRD-4) at Month
      12 in the tacrolimus 1.5-3 ng/ml versus the 4-7 ng/ml group. Secondary endpoints
      included incidence of biopsy-proven acute rejection (BPAR; Months 4-12) and
      serious adverse events (SAEs; Months 0-12). Statistical significance was not
      achieved for the primary endpoint (mean eGFR: 57.1 vs. 51.7 ml/min/1.73 m(2)),
      potentially due to overlapping of achieved tacrolimus exposure levels (Month 12
      mean +/- SD, tacrolimus 1.5-3 ng/ml: 3.4 +/- 1.4; tacrolimus 4-7 ng/ml: 5.5 +/-
      2.0 ng/ml). BPAR (months 4-12) and SAE rates were comparable between groups (2.7%
      vs. 1.1% and 58.7% vs. 51.3%; respectively). Everolimus-facilitated tacrolimus
      minimization, to levels lower than previously investigated, achieved good renal
      function, low BPAR and graft-loss rates, and an acceptable safety profile in
      renal transplantation over 12 months although statistically superior renal
      function of the 1.5-3 ng/ml tacrolimus group was not achieved.

PMID- 22471346
TI  - Light-controlled plasmon switching using hybrid metal-semiconductor
      nanostructures.
AB  - We present a proof of concept for the dynamic control over the plasmon resonance
      frequencies in a hybrid metal-semiconductor nanoshell structure with Ag core and
      TiO(2) coating. Our method relies on the temporary change of the dielectric
      function epsilon of TiO(2) achieved through temporarily generated electron-hole
      pairs by means of a pump laser pulse. This change in epsilon leads to a blue
      shift of the Ag surface plasmon frequency. We choose TiO(2) as the environment of
      the Ag core because the band gap energy of TiO(2) is larger than the Ag surface
      plasmon energy of our nanoparticles, which allows the surface plasmon being
      excited without generating electron-hole pairs in the environment at the same
      time. We calculate the magnitude of the plasmon resonance shift as a function of
      electron-hole pair density and obtain shifts up to 126 nm at wavelengths around
      460 nm. Using our results, we develop the model of a light-controlled surface
      plasmon polariton switch.

PMID- 22471347
TI  - Early events in helix unfolding under external forces: a milestoning analysis.
AB  - Initial events of helix breakage as a function of load are considered using
      molecular dynamics simulations and milestoning analysis. A helix length of ~100
      amino acids is considered as a model for typical helices found in molecular
      machines and as a model that minimizes end effects for early events of unfolding.
      Transitions of individual amino acids (averaged over the helix's interior
      residues) are examined and its surrounding hydrogen bonds are considered. Dense
      kinetic networks are constructed that, with milestoning analysis, provide the
      overall kinetics of early breakage events. Network analysis and selection of
      MaxFlux pathways illustrate that load impacts unfolding mechanisms in addition to
      time scales. At relatively high (100 pN) load levels, the principal intermediate
      is the 3(10)-helix, while at relatively low (10 pN) levels the pi-helix is
      significantly populated, albeit not as an unfolding intermediate. Coarse
      variables are examined at different levels of resolution; the rate of unfolding
      illustrates remarkable stability under changes in the coarsening. Consistent
      prediction of about ~5 ns for the time of a single amino-acid unfolding event are
      obtained. Hydrogen bonds are much faster coarse variables (by about 2 orders of
      magnitude) compared to backbone torsional transition, which gates unfolding and
      thereby provides the appropriate coarse variable for the initiation of unfolding.
      Results provide an atomic description of "catch-bond" behavior, based on
      alternative pathways, in which unfolding of a simple protein structural element
      occurs over longer timescales for intermediate (10 pN) loads than for zero (0 pN)
      or large (100 pN) loads.

PMID- 22471348
TI  - Effectiveness of medical and surgical therapies for lower urinary tract symptoms
      in the community setting.
AB  - Study Type - Therapy (outcomes research) Level of Evidence 2c. What's known on
      the subject? and What does the study add? It is known that benign prostatic
      hyperplasia is a common condition affecting most men by the age of 80 years.
      There are multiple treatment options available, including both medical and
      surgical interventions. However, what is not known is how affective the different
      types of interventions are in the general population. Previous studies have
      focused on centre-specific data. What is unique about our study is that it is a
      prospective cross-section analysis of a community cohort of men. Through this
      study we were able to assess the outcomes in the general population as opposed to
      in a high-volume surgical centre. Our findings show that in this community
      medical management was poor at symptomatic improvement, whereas surgical
      intervention produced the best improvement. OBJECTIVE: * To describe the use and
      symptomatic outcomes of different therapies for lower urinary tract symptoms
      (LUTS) in a community-based population of men followed for 17 years. PATIENTS AND
      METHODS: * Data from a randomly selected cohort of 2184 men, aged 40-79 years in
      1990, from Olmsted County, Minnesota, USA were included in the study.
      Participants completed a questionnaire similar to the American Urological
      Association Symptom Index (AUASI) and reported on incontinence. * Men were
      followed biennially through 2007 (median follow-up: 13.7 years; Q1, Q3: 8.8,
      15.7). Medical and surgical treatments for LUTS were reported on biennial
      questionnaires and abstracted from community medical records. RESULTS: * Overall,
      610 (28%) men received medical or surgical therapy for treatment of LUTS.
      Patients undergoing vaporization and transurethral resection of the prostate
      (TURP) had the highest pre-intervention AUASI scores (P < 0.001) and the most
      rapid increase in scores over time (P= 0.002) compared with those treated with
      medications or no therapy. After intervention, symptom progression slowed in all
      treatment groups. * However, the greatest improvement in AUASI score (median %
      change) was observed in the TURP group: -27.45%. The TURP group also reported a
      significant decrease in incontinence after surgery (% change): TURP: -22.58%.
      CONCLUSION: * All therapies were effective at slowing the progression of LUTS,
      but only TURP patients reported a significant decrease in both LUTS and
      incontinence after therapy.

PMID- 22471349
TI  - Quantitative assessment of shockwave lithotripsy accuracy and the effect of
      respiratory motion.
AB  - BACKGROUND AND PURPOSE: Effective stone comminution during shockwave lithotripsy
      (SWL) is dependent on precise three-dimensional targeting of the shockwave.
      Respiratory motion, imprecise targeting or shockwave alignment, and stone
      movement may compromise treatment efficacy. The purpose of this study was to
      evaluate the accuracy of shockwave targeting during SWL treatment and the effect
      of motion from respiration. PATIENTS AND METHODS: Ten patients underwent SWL for
      the treatment of 13 renal stones. Stones were targeted fluoroscopically using a
      Healthtronics Lithotron (five cases) or Dornier Compact Delta II (five cases)
      shockwave lithotripter. Shocks were delivered at a rate of 1 to 2 Hz with ramping
      shockwave energy settings of 14 to 26 kV or level 1 to 5. After the low energy
      pretreatment and protective pause, a commercial diagnostic ultrasound (US)
      imaging system was used to record images of the stone during active SWL
      treatment. Shockwave accuracy, defined as the proportion of shockwaves that
      resulted in stone motion with shockwave delivery, and respiratory stone motion
      were determined by two independent observers who reviewed the ultrasonographic
      videos. RESULTS: Mean age was 51 +/- 15 years with 60% men, and mean stone size
      was 10.5 +/- 3.7 mm (range 5-18 mm). A mean of 2675 +/- 303 shocks was delivered.
      Shockwave-induced stone motion was observed with every stone. Accurate targeting
      of the stone occurred in 60% +/- 15% of shockwaves. CONCLUSIONS: US imaging
      during SWL revealed that 40% of shockwaves miss the stone and contribute solely
      to tissue injury, primarily from movement with respiration. These data support
      the need for a device to deliver shockwaves only when the stone is in target. US
      imaging provides real-time assessment of stone targeting and accuracy of
      shockwave delivery.

PMID- 22471350
TI  - Emotional communication in families of conduct problem children with high versus
      low callous-unemotional traits.
AB  - This study examined relationships between parent-child emotional communication
      and callous-unemotional (CU) traits and conduct problems. References to negative
      and positive emotions made by clinic-referred boys (3-9 years) and their parents
      were coded from direct observations of family interactions involving the
      discussion of shared emotional experiences. Although frequencies of parents'
      emotion expression did not generally relate to levels of CU traits, boys higher
      on CU traits were observed to be more expressive of negative emotions in
      conversation with their caregivers-specifically for sadness and fear. Independent
      coders did not judge these children to be less genuine in their emotion
      expression compared to their low-CU counterparts. We also examined whether CU
      traits moderated the relationship between parents' focus on emotions and conduct
      problem severity. Higher levels of maternal focus on negative emotions were found
      to be associated with lower conduct problems in high-CU boys but related to
      higher conduct problems in low-CU boys. Frequencies of fathers' emotional
      communication were unrelated to either child CU traits or conduct problems. We
      discuss the implications of these findings for the conceptualization of CU traits
      in preadolescent children, and interventions for conduct problems in children
      elevated on these traits.

PMID- 22471351
TI  - Eye care utilization by older adults in low, middle, and high income countries.
AB  - BACKGROUND: The risk of visual impairment increases dramatically with age and
      therefore older adults should have their eyes examined at least every 1 to 2
      years. Using a world-wide, population-based dataset, we sought to determine the
      frequency that older people had their eyes examined. We also examined factors
      associated with having a recent eye exam. METHODS: The World Health Surveys were
      conducted in 70 countries throughout the world in 2002-2003 using a random, multi
      stage, stratified, cluster sampling design. Participants 60 years and older from
      52 countries (n = 35,839) were asked "When was the last time you had your eyes
      examined by a medical professional?". The income status of countries was
      estimated using gross national income per capita data from 2003 from the World
      Bank website. Prevalence estimates were adjusted to account for the complex
      sample design. RESULTS: Overall, only 18% (95% CI 17, 19) of older adults had an
      eye exam in the last year. The rate of an eye exam in the last year in low, lower
      middle, upper middle, and high income countries was 10%, 24%, 22%, and 37%
      respectively. Factors associated with having an eye exam in the last year
      included older age, female gender, more education, urban residence, greater
      wealth, worse self-reported health, having diabetes, and wearing glasses or
      contact lenses (p < 0.05). CONCLUSIONS: Given that older adults often suffer from
      age-related but treatable conditions, they should be seen on a regular basis to
      prevent visual impairment and its disabling consequences.

PMID- 22471352
TI  - A common genetic variant of FCN3/CD164L2 is associated with essential
      hypertension in a Chinese population.
AB  - Ficolin-3, encoded by FCN3, is the predominant recognition molecule of lectin
      pathway for the activation of complement component 3 (C3), which is an important
      risk factor for the development of hypertension. In our previous study, we found
      the complement system including ficolin-3 was overrepresented in the serum of
      type 2 diabetic patients. Since type 2 diabetes shares some pathogenic
      components, including excessive serum C3, with hypertension, this study aims to
      test the hypothesis that common variants at FCN3 might be associated with
      essential hypertension in our Chinese population. A total of 1797 subjects were
      recruited. Of them, 573 were with essential hypertension. Based on HapMap data,
      three tagging single nucleotide polymorphisms (rs2504778, rs10794501, and
      rs3813800) in FCN3/CD164L2 region were selected for genotyping by using
      MassARRAY. Logistic regression analysis was performed to evaluate the genetic
      effects on the prevalence of hypertension after adjusting for covariates.
      rs2504778, which locates in the upstream of FCN3 and in the intron of CD164L2,
      was found to be significantly associated with hypertension after adjusting for
      covariates (OR = 1.28, 95% CI: 1.05, 1.55, P = .015). Correction for multiple
      testing did not remarkably attenuate the significance (empirical P = .042 with 10
      000 permutations). rs2504778 also showed a nominal association with systolic
      blood pressure (P = .044) in the quantitative trait analysis. No evidence of
      correlation with hypertension and blood pressure was observed for rs10794501 and
      rs3813800. We found that a common variant of FCN3/CD164L2 is associated with
      hypertension in our Chinese population. More studies with larger sample size are
      needed to confirm this finding.

PMID- 22471353
TI  - Brain structure and aging in chronic temporal lobe epilepsy.
AB  - PURPOSE: To characterize differences in brain structure and their patterns of age
      related change in individuals with chronic childhood/adolescent onset temporal
      lobe epilepsy compared with healthy controls. METHODS: Subjects included
      participants with chronic temporal lobe epilepsy (n = 55) of mean
      childhood/adolescent onset and healthy controls (n = 53), age 14-60 years. Brain
      magnetic resonance imaging (MRI) studies (1.5 T) were processed using FreeSurfer
      to obtain measures of lobar thickness, area, and volume as well as volumes of
      diverse subcortical structures and cerebellum. Group differences were explored
      followed by cross-sectional lifespan modeling as a function of age. KEY FINDINGS:
      Anatomic abnormalities were extensive in participants with chronic temporal lobe
      epilepsy including distributed subcortical structures (hippocampus, thalamus,
      caudate, and pallidum), cerebellar gray and white matter, total cerebral gray and
      white matter; and measures of cortical gray matter thickness, area, or volume in
      temporal (medial, lateral) and extratemporal lobes (frontal, parietal).
      Increasing chronologic age was associated with progressive changes in diverse
      cortical, subcortical, and cerebellar regions for both participants with epilepsy
      and controls. Age-accelerated changes in epilepsy participants were seen in
      selected areas (third and lateral ventricles), with largely comparable patterns
      of age-related change across other regions of interest. SIGNIFICANCE: Extensive
      cortical, subcortical, and cerebellar abnormalities are present in participants
      with mean chronic childhood/adolescent onset temporal lobe epilepsy implicating a
      significant neurodevelopmental impact on brain structure. With increasing
      chronologic age, the brain changes occurring in epilepsy appear to proceed in a
      largely age-appropriate fashion compared to healthy controls, the primary
      exception being age-accelerated ventricular expansion (lateral and third
      ventricles). These cumulative structural abnormalities appear to represent a
      significant anatomic burden for persons with epilepsy, the consequences of which
      remain to be determined as they progress into elder years.

PMID- 22471355
TI  - Electrochemical and spectroscopic effects of mixed substituents in bis(phenolate)
      copper(II) galactose oxidase model complexes.
AB  - Nonsymmetric substitution of salen (1(R(1),R(2))) and reduced salen
      (2(R(1),R(2))) Cu(II)-phenoxyl complexes with a combination of -(t)Bu, -S(i)Pr,
      and -OMe substituents leads to dramatic differences in their redox and
      spectroscopic properties, providing insight into the influence of the cysteine
      modified tyrosine cofactor in the enzyme galactose oxidase (GO). Using a modified
      Marcus-Hush analysis, the oxidized copper complexes are characterized as Class II
      mixed-valent due to the electronic differentiation between the two substituted
      phenolates. Sulfur K-edge X-ray absorption spectroscopy (XAS) assesses the degree
      of radical delocalization onto the single sulfur atom of nonsymmetric
      [1((t)Bu,SMe)](+) at 7%, consistent with other spectroscopic and electrochemical
      results that suggest preferential oxidation of the -SMe bearing phenolate.
      Estimates of the thermodynamic free-energy difference between the two localized
      states (DeltaG(o)) and reorganizational energies (lambda(R(1)R(2))) of
      [1(R(1),R(2))](+) and [2(R(1),R(2))](+) lead to accurate predictions of the
      spectroscopically observed IVCT transition energies. Application of the modified
      Marcus-Hush analysis to GO using parameters determined for [2(R(1),R(2))](+)
      predicts a nu(max) of ~13600 cm(-1), well within the energy range of the broad
      Vis-NIR band displayed by the enzyme.

PMID- 22471356
TI  - Behavioural phenotypes and special educational needs: is aetiology important in
      the classroom?
AB  - BACKGROUND: A number of genetic conditions with associated intellectual
      disability and/or special educational needs have increasingly well-defined
      behavioural phenotypes. Thus, the concept of 'behavioural phenotype' and
      aetiology of intellectual disability may be important with regard to school-based
      interventions. METHOD: The evidence for distinctive cognitive and behavioural
      aspects of five of the most common genetic syndromes (Down syndrome, fragile X
      syndrome, Williams syndrome, Prader-Willi syndrome and velo-cardio-facial
      syndrome) associated with special educational needs is reviewed with respect to
      key studies and findings. The possible utility of aetiology-related interventions
      in education is discussed with reference to arguments for and against such
      approaches with respect to published guidelines and published research. RESULTS:
      Behavioural phenotypes are probabilistic and many children with a specific
      genetic syndrome will share commonalities with other children with other genetic
      syndromes and within syndrome variability is not uncommon. There is evidence that
      teachers and parents have limited knowledge of aspects of the proposed cognitive
      and behaviour profiles associated with the reviewed syndromes. While there are
      published guidelines in the area of learning and behaviour for each of the five
      reviewed syndromes there is a limited amount of evidence of the efficacy of such
      approaches in school settings. CONCLUSION: It is likely that knowing the
      aetiology of a child's special educational needs will be helpful for staff who
      work in school settings in relation to cognitive and behavioural implications.
      However, how such knowledge might inform teaching practice or behavioural
      interventions has not been studied. A model is proposed that might help inform
      educators about the possible role of aetiology in the classroom.

PMID- 22471357
TI  - Osteoarthritis of the knee and hip. Part I: aetiology and pathogenesis as a basis
      for pharmacotherapy.
AB  - OBJECTIVES: Osteoarthritis (OA) of the knee and hip is among the most frequent
      and debilitating arthritic conditions. Aside from surgical intervention in severe
      cases, conventional treatment involves relieving painful symptoms with non
      steroidal anti-inflammatory drugs (NSAIDs), narcotic and non-narcotic (weak)
      analgesics and physical therapy. To obtain insight into the extent of
      pathological changes in hip and knee OA we reviewed current literature on the
      pathogenesis of this state as a basis for current pharmacotherapy options. KEY
      FINDINGS: Key features of the pathological joint changes in OA include: cartilage
      destruction by pro-inflammatory cytokines, matrix metalloproteinases and
      prostaglandins, which promote a catabolic environment; subchondral bone
      remodelling and resorption; hypertrophic differentiation of chondrocytes;
      neovascularisation of synovial tissue; and focal calcification of joint
      cartilage. Despite the central involvement of hyaline cartilage in OA
      pathogenesis, the source of pain likely stems from the richly innervated
      synovium, subchondral bone and periosteum components of the joint. Tissue damage
      during joint degeneration generates nociceptive stimuli. The presence of
      inflammatory mediators, including bradykinin, prostaglandins and leukotrienes,
      lowers the threshold of the Adelta and C pain fibres, resulting in a heightened
      response to painful stimuli. SUMMARY: It is our opinion that it is important to
      base and centre the management of OA patients on the severity of patient
      important outcomes, rather than purely an assessment of damage to the joint. The
      joint damage, as interpreted from radiographs, is not necessarily representative
      of the symptoms experienced. The management of OA primarily comprises
      pharmacological therapy, surgical interventions and various non-pharmacological
      interventions.

PMID- 22471358
TI  - Osteoarthritis of the knee and hip. Part II: therapy with ibuprofen and a review
      of clinical trials.
AB  - OBJECTIVES: We review the pharmacological properties and clinical evidence
      pertaining to the efficacy of ibuprofen as a first-line treatment in hip and knee
      osteoarthritis (OA). In the context of our previous paper's exploration of the
      aetiology and pathogenesis of OA as a basis for pharmacotherapy, we discuss the
      pharmacokinetics (PK) and clinical pharmacodynamics (PD) of ibuprofen relevant to
      OA. KEY FINDINGS: Although widely used, the benefits and risks of ibuprofen,
      especially compared with other non-steroidal anti-inflammatory drugs (NSAIDs) and
      placebo, have only recently been evaluated in OA of the hip and knee in
      randomized-controlled clinical trials (RCT). The efficacy and occurrence of
      adverse reactions from ibuprofen was compared with placebo in a structural review
      of the literature and systematic review of RCTs in large-scale clinical trials.
      Ibuprofen has been found to result in approximately 50-60% improvement over
      placebo in WOMAC scores, including those reflecting inflammatory joint pain in
      knee and hip OA or other indices of pain, disability and impaired function. Mega
      trials performed in comparison with the newer NSAIDs, the coxibs, have shown that
      ibuprofen has comparable therapeutic benefits and although serious
      gastrointestinal conditions are sometimes more frequent after short-term
      treatment, longer-term (several months) therapy in OA reduces the advantages of
      the coxibs over other NSAIDs including ibuprofen. Cardiovascular risk, though
      present with coxibs and some NSAIDs in OA, is lower or slightly so with ibuprofen
      compared with coxibs. SUMMARY: Ibuprofen is effective and relatively safe
      (especially at low over-the-counter doses and in the short term) for mild-to
      moderate OA of the knee and hip. The PK properties of ibuprofen in OA (short
      plasma t1/2) confer advantages of this drug for OA, while evidence for clinically
      relevant PD benefits in joints of patients with OA, though limited, is suggestive
      of local anti-inflammatory activity.

PMID- 22471359
TI  - Exendin-4 treatment enhances L-DOPA evoked release of striatal dopamine and
      decreases dyskinetic movements in the 6-hydoxydopamine lesioned rat.
AB  - OBJECTIVES: To determine whether the glucagon-like 1 peptide analogue exendin-4
      (EX-4) augments the neurochemical effects of a single L-DOPA treatment and
      whether EX-4 can decrease L-DOPA induced dyskinesias (LIDS). METHODS: Rats were
      lesioned with 6-hydroxydopamine (6-OHDA) and 7 days later given EX-4 for 7 days.
      The following day, rats were given L-DOPA and extracellular dopamine was
      measured. The animals were then killed to determine tissue dopamine. To study
      LIDS, EX-4 and/or L-DOPA were co-administered daily, 7 days after 6-OHDA. LIDS
      were determined on Days 2, 4, 8, 12 and 16 prior to neurochemical assessment. KEY
      FINDINGS: EX-4 reduced 6-OHDA induced damage. Acute effects of L-DOPA were
      potentiated by EX-4 in lesioned rats. Treatments with EX-4 caused a progressive
      reduction in LIDS. CONCLUSIONS: EX-4 treatment potentiates the effects of a
      single dose of L-DOPA. This augmentation indicates that lower L-DOPA doses might
      be used to the same effect in patients. The reduction in LIDS suggests that co
      treatment with EX-4 could allow the use of L-DOPA with fewer side-effects and
      possibly therefore allow earlier introduction of L-DOPA in the clinic.

PMID- 22471360
TI  - Mechanisms of action of zinc on rat intestinal epithelial electrogenic ion
      secretion: insights into its antidiarrhoeal actions.
AB  - OBJECTIVES: Zinc is a useful addition to oral rehydration therapy for acute
      diarrhoea. We have assessed the mechanism of its epithelial antisecretory action
      when intestinal epithelial tight junctions were pharmacologically opened.
      METHODS: Rat isolated ileal and colonic mucosae were mounted in Ussing chambers
      and exposed to ZnSO(4) (Zn(2+) ) in the presence of secretagogues and inhibition
      of short circuit current (I(sc) ) was measured. KEY FINDINGS: Pre-incubation with
      basolateral but not apical Zn(2+) reduced I(sc) stimulated by forskolin,
      carbachol and A23187. In the presence of the tight junction-opener, cytochalasin
      D, antisecretory effects of apically-applied Zn(2+) were enabled in colon and
      ileum. The apparent permeability coefficient (P(app) ) of Zn(2+) was increased
      1.4- and 2.4-fold across rat ileum and colon, respectively, by cytochalasin D.
      Basolateral addition of Zn(2+) also reduced the I(sc) stimulated by nystatin in
      rat colon, confirming K channel inhibition. In comparison with other inhibitors,
      Zn(2+) was a relatively weak blocker of basolateral K(ATP) and K (Ca2+) channels.
      Exposure of ileum and colon to Zn(2+) for 60 min had minimal effects on
      epithelial histology. CONCLUSIONS: Antisecretory effects of Zn(2+) on intestinal
      epithelia arose in part through nonselective blockade of basolateral K channels,
      which was enabled when tight junctions were open.

PMID- 22471361
TI  - Formulation development of gastroretentive tablets of lamivudine using the
      floating-bioadhesive potential of optimized polymer blends.
AB  - OBJECTIVES: The current studies entail successful formulation of optimized
      gastroretentive tablets of lamivudine using the floating-bioadhesive potential of
      carbomers and cellulosic polymers, and their subsequent in-vitro and in-vivo
      evaluation in animals and humans. METHODS: Effervescent floating-bioadhesive
      hydrophilic matrices were prepared and evaluated for in-vitro drug release,
      floatation and ex-vivo bioadhesive strength. The optimal composition of polymer
      blends was systematically chosen using central composite design and overlay
      plots. Pharmacokinetic studies were carried out in rabbits, and various levels of
      in-vitro/in-vivo correlation (IVIVC) were established. In-vivo gamma
      scintigraphic studies were performed in human volunteers using (99m) Tc to
      evaluate formulation retention in the gastric milieu. KEY FINDINGS: The optimized
      formulation exhibited excellent bioadhesive and floatational characteristics
      besides possessing adequate drug-release control and pharmacokinetic extension of
      plasma levels. The successful establishment of various levels of IVIVC
      substantiated the judicious choice of in-vitro dissolution media for simulating
      the in-vivo conditions. In-vivo gamma scintigraphic studies ratified the
      gastroretentive characteristics of the optimized formulation with a retention
      time of 5 h or more. CONCLUSIONS: Besides unravelling the polymer synergism, the
      study helped in developing an optimal once-a-day gastroretentive drug delivery
      system with improved bioavailability potential exhibiting excellent swelling,
      floating and bioadhesive characteristics.

PMID- 22471362
TI  - A herbal-drug interaction study of keishi-bukuryo-gan, a traditional herbal
      preparation used for menopausal symptoms, in healthy female volunteers.
AB  - OBJECTIVES: Many patients use herbal medicines to relieve menopausal symptoms.
      Keishi-bukuryo-gan contains five herbal components, and has been used for
      treating hypermenorrhoea, dysmenorrhoea and menopausal symptoms in Asian
      countries. In this study, we investigated the potential herb-drug interactions of
      keishi-bukuryo-gan in healthy female subjects. METHODS:   Thirty-one healthy
      females (20-27 years) were studied to evaluate their baseline activity of
      cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N
      acetyltransferase 2 (NAT2) based on the urinary metabolic indices of an 8-h urine
      sample collected after a 150-mg dose of caffeine and a 30-mg dose of
      dextromethorphan, and also the urinary excretion ratio of 6beta-hydroxycortisol
      to cortisol. Thereafter, the subjects received 3.75g of keishi-bukuryo-gan twice
      daily for seven days, and underwent the same tests on post-dose day 7. KEY
      FINDINGS: The geometric mean phenotypic index for CYP1A2 significantly decreased
      by 16% on day 7 compared with the baseline (P=0.026). Keishi-bukuryo-gan did not
      alter the indices for CYP2D6, CYP3A, XO and NAT2. CONCLUSIONS: Keishi-bukuryo-gan
      may inhibit the activity of CYP1A2, which is predominantly involved in oestrogen
      metabolism. However, TJ-25 is unlikely to participate in herb-drug interactions
      involving medications predominantly metabolized by CYP2D6, CYP3A, XO and NAT2. K

PMID- 22471363
TI  - The effect of poloxamer 407 on the functional properties of HDL in mice.
AB  - OBJECTIVES: There is an inverse relationship between high-density lipoprotein
      (HDL) and heart disease. HDL possesses not only both antioxidant and anti
      inflammatory properties, but also anti-thrombotic and endothelial function
      promoting qualities. However, it is not only the serum concentration of HDL that
      is important, but also the 'functional' quality of the HDL. The objective was to
      determine the functional status of HDL in a well-established mouse model of
      dyslipidaemia and atherosclerosis induced by the administration of a block
      copolymer (poloxamer 407; P-407). METHODS: C57BL/6 mice were administered a
      single intraperitoneal dose of P-407 (0.5g/kg) and blood was collected at 24h
      post-dosing. HDL was isolated from controls (control HDL) and P-407-treated (P
      407 HDL) mice and used to test its anti-inflammatory properties in vitro.
      Additionally, antioxidant enzymes associated with HDL, namely, platelet
      activating factor-acetylhydrolase (PAF-AH) and paraoxonase (PON), were evaluated
      for any potential reduction in their biological activity. KEY FINDINGS: A single
      injection of P-407 in C57BL/6 mice resulted in a marked decrease in the levels of
      HDL-cholesterol and phospholipids. HDL particle size significantly increased,
      primarily due to remodelling of HDL with triglyceride. It was demonstrated that
      (i) long-chain saturated fatty acids were higher and the n-3/n-6 fatty acid ratio
      was significantly lower for P-407 HDL compared with control HDL, and (ii) P-407
      HDL lost its capacity to inhibit tumour necrosis factor-alpha (TNF-alpha)-induced
      vascular cell adhesion molecule-1 (VCAM-1) expression compared with control HDL.
      Additionally, P-407 HDL was not able to neutralize lipopolysaccharide and inhibit
      subsequent TNF-alpha production compared with control HDL. The biological
      activity of platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase
      (PON) decreased in direct proportion to the circulating levels of both HDL
      cholesterol and apolipoprotein (apoA-1). CONCLUSIONS: Combination of previously
      reported findings in P-407-treated mice, such as (i) production of both oxidized
      LDL and malondialdehyde, and (ii) profound elevations in the soluble forms of
      intercellular adhesion molecule-1 (ICAM-1), VCAM-1, and E-selectin, with the
      present results, would strongly suggest that HDL in P-407-treated mice is
      rendered dysfunctional. Thus, these findings help to explain why P-407-treated
      mice begin to form aortic atherosclerotic lesions about one month after
      initiating P-407 treatment.

PMID- 22471364
TI  - Spectroscopic investigations of the molecular interaction of anticancer drug
      mitoxantrone with non-ionic surfactant micelles.
AB  - OBJECTIVES: The aim of this study was to investigate the interaction of the
      anticancer drug mitoxantrone with non-ionic micelles, as simple model systems of
      biological membranes. METHODS: UV-VIS absorption spectroscopy was used to
      quantify the drug-surfactant micelle interactions in terms of the binding
      constant and the micelle-water partition coefficient of the drug. KEY FINDINGS:
      Interaction of mitoxantrone with non-ionic micelles reduces the dimerization
      process of mitoxantrone, the drug molecules being encapsulated into micelles as
      monomer. The strength of the interaction between mitoxantrone and non-ionic
      micelles is higher at pH10 than at pH7.4, and depends on the surfactant in the
      order Tween 80>Tween 20>Triton X-100. The higher partition coefficient at pH10
      compared to pH7.4 suggests that at basic pH the deprotonated mitoxantrone is
      incorporated more efficiently into the hydrophobic medium of non-ionic micelles
      compared to physiological pH, when the protonated drug is predominant.
      CONCLUSIONS: These results on simple model systems miming the drug-membrane
      interactions contribute to the elucidation of the behaviour of the drug in vivo,
      as well as the possible utilization of surfactant micelles as drug carriers.

PMID- 22471365
TI  - Platycodon grandiflorum modifies adipokines and the glucose uptake in high-fat
      diet in mice and L6 muscle cells.
AB  - OBJECTIVES: Obesity and diabetes have become the most common human health
      problems worldwide. Obesity's contribution to type 2 diabetes might be due to
      dysregulation of adipokines and glucose uptake. METHODS: In this study, we
      performed in-vivo and in-vitro studies to evaluate the effects of Platycodon
      grandiflorum extract (PGE) on adipokines and glucose uptake. Before study,
      platycodin D concentrations were analysed by HPLC in PGE prepared in water, in
      50% ethanol and in 80% ethanol, and we selected the 80% ethanol extract as the
      PGE for this study based on the HPLC results. KEY FINDINGS: We found that
      inclusion of PGE in the high-fat diet (HFD) markedly attenuated food intake, body
      weight, epididymal fat weight, adipocyte size and blood glucose levels by the
      oral glucose tolerance test in mice, and maintained serum levels of adiponectin,
      resistin, leptin, fructosamine and triglycerides. Gene expression analysis
      revealed that PGE up-regulated adiponectin, and down-regulated TNF-alpha and
      leptin in fat tissue. In L6 muscle cells in vitro, PGE increased insulin
      stimulated glucose uptake. CONCLUSIONS:   We conclude that PGE may improve
      obesity in mice fed an HFD and glucose uptake in L6 muscle cells by modifying
      adipokines, and could offer clinical benefits as a supplement to treat obesity
      and diabetes.

PMID- 22471366
TI  - Investigating paracetamol pharmacokinetics using venous and capillary blood and
      saliva sampling.
AB  - OBJECTIVE: The aim of this study was to develop, validate and apply a high
      performance liquid chromatography (HPLC) assay for analysis of paracetamol,
      paracetamol glucuronide and paracetamol sulfate in plasma (venous and capillary)
      and saliva to study paracetamol pharmacokinetics in healthy volunteers. METHODS:
      Samples were prepared using protein precipitation and analysed using reverse
      phase HPLC with UV detection. This assay was applied to venous and capillary
      plasma and saliva samples from 20 healthy volunteers after paracetamol 1g four
      times daily for three days. KEY FINDINGS: The HPLC assay for paracetamol and its
      metabolites was found to be sensitive and selective in plasma and saliva samples
      over the range 0.05-50 mg/l with an inter- and intraday precision and accuracy
      within 11.2% and 11.1%, respectively. Mean recoveries for all analytes were >
      88%. A study of paracetamol pharmacokinetics in healthy volunteers found close
      agreement between the sampling matrices for paracetamol and metabolites
      (metabolites were not detected in saliva). The value for area under the
      concentration-time curve over the 6h dosing interval of venous plasma (45.3+/
      12.9mg/l.h) was significantly higher than that observed for capillary plasma
      (33.8+/-12.9mg/l.h) or saliva (35.1+/-9.4mg/l.h; P>0.01). CONCLUSIONS: Capillary
      blood and saliva collection were found to be reliable sampling matrices for the
      evaluation of paracetamol pharmacokinetics, although paracetamol metabolites were
      not detected in saliva.

PMID- 22471367
TI  - Synthesis, characterization and in-vitro antitubercular activity of isoniazid
      gelatin conjugate.
AB  - OBJECTIVES: A novel and simple method to synthesize antitubercular-protein
      conjugate by solid phase synthesis was developed employing a carboxypolystyrene
      resin. The aim was to covalently bind a drug with antitubercular activity,
      isoniazid, to a biomacromolecule, gelatin, widely used in the pharmaceutical,
      cosmetic and food industry. METHODS: Calorimetric and (1) H NMR analyses were
      performed to verify the bond formation between the antitubercular drug and
      gelatin. After absorption isoniazid delivers toxic metabolites and so an
      oxidation test with tert-butyl hydroperoxide was performed to assess the amount
      of toxic metabolites released from the prodrug (gelatin linked to isoniazid),
      compared with isoniazid itself. KEY FINDINGS:   Spectrophotometric analysis
      revealed that the protein derivative was an excellent isoniazid prodrug since
      there was a 40% reduction in release of toxic metabolites (isonicotinic acid) by
      the prodrug. The results clearly showed that antitubercular moieties, covalently
      linked to a natural polymer, allowed the introduction of peculiar features for
      specific pharmaceutical applications into the macromolecule. In addition,
      antitubercular activity of the new polymer was determined by Middlebrook 7H11
      medium against Mycobacterium tuberculosis complex. CONCLUSIONS: The new isoniazid
      gelatin conjugate showed significant antitubercular activity and for this reason
      should be useful as an efficacious tool in the treatment of tuberculosis.

PMID- 22471368
TI  - Establishment of a cell-based drug screening model for identifying agonists of
      human peroxisome proliferator-activated receptor gamma (PPARgamma).
AB  - OBJECTIVES: Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a
      critical role in regulation of diverse biological processes, including lipid
      metabolism and adipogenesis, cell division and apoptosis, and is involved in
      variety of disease conditions, such as obesity, atherosclerosis, inflammation and
      tumour. Developing a cell-based reporter gene model targeting PPARgamma would be
      useful to screen human PPARgamma agonists that could be beneficial to patients
      with these diseases. METHODS: We stably co-transfected human embryonic kidney
      (HEK) cell line 293T cells with phPPARgamma-IRES2-EGFP vector to express human
      PPARgamma (hPPARgamma), a reporter vector pPPRE*3-TK-LUC, and control vector pRL
      CMV. The efficiency of the co-transfection was evaluated with flow cytometry of
      hPPARgamma expressing cells. Specificity of hPPARgamma activity was determined by
      dual luciferase reporter assay of co-transfected cells exposed to PPARgamma
      agonist rosiglitazone, PPARalpha agonist WY14643 and retinoic acid receptor alpha
      (RARalpha) agonist all-trans-retinoic acid (ATRA). KEY FINDINGS: The phPPARgamma
      IRES2-EGFP co-transfected HEK293T cells showed concentration- and time-dependent
      luciferase induction upon exposure to the rosiglitazone, while WY14643 and ATRA
      were unable to activate the co-transfected HEK293T cells. CONCLUSIONS: These data
      indicated that the HEK293T cells could be stably transfected with hPPARgamma.
      This cell-based drug screening platform could be used targeting specific nuclear
      receptor of hPPARgamma with effectiveness and specificity for hPPARgamma agonists
      discovery.

PMID- 22471369
TI  - Caspase-mediated pro-apoptotic interaction of panaxadiol and irinotecan in human
      colorectal cancer cells.
AB  - OBJECTIVES: Panaxadiol is a purified sapogenin of ginseng saponins that exhibits
      anticancer activity. Irinotecan is a second-line anticancer drug, but clinical
      treatment with irinotecan is limited due to its side effects. In this study, we
      have investigated the possible synergistic anticancer effects of panaxadiol and
      irinotecan on human colorectal cancer cells and explored the potential role of
      apoptosis in their synergistic activity. KEY FINDINGS: The combination of
      panaxadiol and irinotecan significantly enhanced antiproliferative effects in HCT
      116 cells (P< 0.05). Cell cycle analysis demonstrated that combining irinotecan
      treatment with panaxadiol significantly increased the G1-phase fractions of
      cells, compared with irinotecan treatment alone. In apoptotic assays, the
      combination of panaxadiol and irinotecan significantly increased the percentage
      of apoptotic cells compared with irinotecan alone (P<0.01). Increased activity of
      caspase-3 and caspase-9 was observed after treating with panaxadiol and
      irinotecan. The synergistic apoptotic effects were supported by docking analysis,
      which demonstrated that panaxadiol and irinotecan bound two different chains of
      the caspase-3 protein. CONCLUSIONS: Data from this study suggested that caspase-3
      and caspase-9-mediated apoptosis may play an important role in the panaxadiol
      enhanced antiproliferative effects of irinotecan on human colorectal cancer
      cells.

PMID- 22471370
TI  - Selective inhibitory action of Biginelli-type dihydropyrimidines on
      depolarization-induced arterial smooth muscle contraction.
AB  - OBJECTIVES: Dihydropyridine calcium channel blockers have some disadvantages such
      as light sensitivity and relatively short plasma half-lives. Stability of
      dihydropyrimidines analogues could be of advantage, yet they remain less well
      characterized. We aimed to test four newly synthesized Biginelli-type
      dihydropyrimidines for their calcium channel blocking activity on rat isolated
      aorta. METHODS: Dihydropyrimidines (compounds A-D) were prepared by the Biginelli
      like three-component condensation of benzaldehydes with urea/thiourea and
      dimethyl or diethyl acetone-1,3-dicarboxylate, and their physicochemical
      properties and effects on depolarization-induced and noradrenaline-induced
      contractions of rat isolated aorta were evaluated. KEY FINDINGS:
      Dihydropyrimidines A and C blocked KCl-induced contraction only weakly (
      log(IC50)=5.03 and 3.73, respectively), while dihydropyrimidine D (
      log(IC50)=7.03) was almost as potent as nifedipine (-log(IC50)=8.14). Washout
      experiments revealed that dihydropyrimidine D may bind strongly to the L-type
      calcium channel or remains bound to membrane. All tested dihydropyrimidines only
      marginally inhibited noradrenaline-induced contractions of rat isolated aorta
      (20% reduction of noradrenaline E(max) ), indicating a more selective action on L
      type calcium channel than nifedipine with 75% inhibition of noradrenaline E(max)
      at 10(-4) m nifedipine). CONCLUSIONS: Compounds A and, particularly, D are potent
      calcium channel blockers in vitro, with a better selectivity in inhibiting
      depolarization-induced arterial smooth muscle contraction than nifedipine.

PMID- 22471371
TI  - Tyrosine-like condensed derivatives as tyrosinase inhibitors.
AB  - OBJECTIVES: We report the pharmacological evaluation of a new series of 3
      aminocoumarins differently substituted with hydroxyl groups, which have been
      synthesized because they include in their structures the tyrosine fragment
      (tyrosine-like compounds), with the aim of discovering structural features
      necessary for tyrosinase inhibitory activity. METHODS: The synthesized compounds
      4 and 7-9 were evaluated in vitro as mushroom tyrosinase inhibitors. KEY
      FINDINGS: Two of the described compounds showed lower IC50 (concentration giving
      50% inhibition of tyrosinase activity) than umbelliferone, used as a reference
      compound. CONCLUSIONS: Compound 7 (IC50=53um) was the best tyrosinase inhibitor
      of this small series, having an IC50 value 10-fold lower than umbelliferone.
      Compound 7 (3-amino-7-hydroxycoumarin) had amino and hydroxyl groups precisely
      mimicking the same positions that both groups occupy on the tyrosine molecule.

PMID- 22471372
TI  - Involvement of inflammation in severe post-operative pain demonstrated by pre
      surgical and post-surgical treatment with piroxicam and ketorolac.
AB  - OBJECTIVES: Post-operative pain is considered to involve inflammation caused by
      tissue injury. However, the mechanism and timing of the involvement of
      inflammation in the post-operative pain remain complicated because they can vary
      among different types of surgery. In this study a rat incision model was used to
      investigate how inflammation induced by cyclooxygenases (COXs) is involved in
      severe post-operative pain. METHODS: Longitudinal incision with a length of 1cm
      was made through skin and fascia on the right hind paw of rats, starting 0.5cm
      from the edge of the heel and extending towards the toes. Allodynia was evaluated
      using the von Frey hair test and its degree was recorded as the paw withdrawal
      threshold (PWT). Two non-steroidal anti-inflammatory drugs (NSAIDs), piroxicam
      and ketorolac, were given to rats after or before surgery, and the effects of the
      drugs on allodynia induced by the hind paw incision were examined. KEY FINDINGS:
      The PWT reduction reached a sub-maximal level at 3h, a maximal level at one day
      after the surgery and lasted for more than 8 days, with the parallel development
      of inflammation (characterized by cell infiltration and oedema). Treatment with
      morphine (1mg/kg, s.c.) at one day after the surgery showed a significant anti
      allodynic effect. Treatment with either piroxicam (10mg/kg, p.o.) or ketorolac
      (10mg/kg, p.o.) at one day after the surgery did not exhibit significant anti
      allodynic effect, whereas pre-surgical treatment with each drug showed
      significant anti-allodynic effects at 3h after surgery. CONCLUSIONS: These
      findings suggest the involvement of cyclooxygenases in evoking pain that occurs
      in the immediate post-operative period, and that an initial suppression of rapid
      inflammation by treatment with NSAIDs before major surgery plays an important
      role in the management of severe post-operative pain.

PMID- 22471373
TI  - Enhancement of anti-inflammatory and antinociceptive actions of red ginseng
      extract by fermentation.
AB  - OBJECTIVES: This work aimed to compare some pharmacological properties of red
      ginseng extract (RG) and fermented red ginseng extract (FRG). METHODS:
      Antinociceptive activity was analysed using the acetic acid-induced abdominal
      constriction response. Anti-inflammatory activity was evaluated using acetic acid
      induced vascular permeability and carrageenan-induced inflammation in the air
      pouch, and analysed through the measurement of nitrite content in the
      lipopolysaccharide (LPS)-stimulated macrophage cells. Anti-angiogenic activity
      was determined using the chick chorioallantoic membrane assay. KEY FINDINGS: In
      vivo anti-inflammatory activity of FRG was stronger than that of RG in two animal
      models, vascular permeability and air-pouch models. In the vascular permeability
      model, the doses of RG and FRG required for half-maximal inhibition (IC50) were
      181 and 59mg/kg, respectively. FRG exhibited significantly stronger
      antinociceptive activity than RG. In the acetic acid-induced abdominal
      constriction response, the IC50 values of RG and FRG were 153 and 27mg/kg,
      respectively. Although both RG and FRG were able to suppress production of nitric
      oxide in the LPS-stimulated RAW264.7 macrophage cells, the suppressive activity
      of FRG appeared to be stronger than that of RG. However, RG and FRG showed
      similar anti-angiogenic activity. CONCLUSIONS: FRG possesses enhanced anti
      inflammatory and antinociceptive activity but similar anti-angiogenic activity
      than RG.

PMID- 22471374
TI  - The effect of photodynamic therapy on contiguous untreated tumor.

PMID- 22471375
TI  - Lacrimal gland lesions in Denmark between 1974 and 2007.
AB  - PURPOSE: To evaluate the incidence rate, distribution, patient characteristics
      and indications for surgical intervention of lacrimal gland lesions in Denmark
      between 1974 and 2007. MATERIAL AND METHODS: All biopsied/surgically removed
      lacrimal gland lesions in Denmark during the period 1974-2007 were identified by
      searching two population-based registries. Specimens were collected and re
      evaluated. The following data were collected: age, gender, indications for
      surgical intervention and local recurrence. RESULTS: A total of 232 lesions from
      210 patients with a histologically verified lesion of the lacrimal gland were
      included. The incidence rate of lacrimal gland lesions was 1.3/1 000 000/year.
      The overall annual age- and gender-adjusted incidence rate more than doubled
      during the study period, owing to an increase in non-malignant lesions.
      Approximately half of the lesions were neoplasms (119) and 55% (66) of these were
      malignant. Dacryops constituted 10% (24), inflammatory lesions 27% (62), normal
      tissue 12% (27), benign tumours 23% (53) and malignant tumours 29% (66). Patients
      with malignant neoplasms were significantly older than patients with benign
      neoplasms (63 versus 48 years, p < 0.001). The indication for surgical
      intervention was suspicion of a tumour in more than 90% of the neoplastic lesions
      and in 30% of the non-neoplastic lesions. CONCLUSION: Lacrimal gland lesions that
      require surgical evaluation are rare in the Danish population and represent a
      wide spectrum of diagnoses, mostly benign. The overall incidence rate of biopsied
      lacrimal gland lesions is increasing.

PMID- 22471376
TI  - Discovery of novel urea-based hepatitis C protease inhibitors with high potency
      against protease-inhibitor-resistant mutants.
AB  - The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was
      identified to be a novel and potent HCV protease inhibitor. We further explored
      this motif by synthesizing additional urea-based inhibitors and by characterizing
      them in replicase HCV protease-resistant mutants assay. Several compounds,
      exemplified by 12, were found to be more potent in HCV replicon assays than
      leading second generation inhibitors such as danoprevir and TMC-435350.
      Additionally, following oral administration, inhibitor 12 was found in rat liver
      in significantly higher concentrations than those reported for both danoprevir
      and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and
      pharmacokinetic properties that warrants further development of this series.

PMID- 22471377
TI  - CD28-specific immunomodulating antibodies: what can be learned from experimental
      models?
AB  - Tolerance induction to alloantigens remains a major challenge in transplant
      immunology. Progress in the last decade of our understanding of T-cell activation
      has led to the development of new immunotherapeutic strategies to replace
      conventional immunosuppression which inhibits the immune system in a nonspecific
      way. In particular, positive and negative costimulatory molecules of the CD28
      family have been consistently demonstrated to be critical for the development of
      productive immune responses as well as the establishment and maintenance of
      peripheral tolerance. However, recent discoveries of novel costimulatory
      interactions confer a novel dimension to the immunoregulatory interactions within
      the B7:CD28 family and compels a revised view within a "quintet" of costimulatory
      molecules: CD28/B7/CTLA-4/PD-L1/ICOSL. Complexity introduced in this more
      detailed costimulatory pathway has important implications in therapeutic
      interventions against human immunological diseases and, especially, highlight the
      fundamental differences in selectively targeting CD28 molecules instead of B7
      counterparts. In this review, we discuss these differences and emphasize
      different CD28-specific immunomodulating strategies evaluated in experimental
      models of transplantation and autoimmune diseases.

PMID- 22471378
TI  - Monitoring physical functioning as the sixth vital sign: evaluating patient and
      practice engagement in chronic illness care in a primary care setting--a quasi
      experimental design.
AB  - BACKGROUND: In Canada, one in three adults or almost 9 million people report
      having a chronic condition. Over two thirds of total deaths result from
      cardiovascular disease, diabetes, cancer and respiratory illness and 77% of
      persons >=65 years have at least one chronic condition. Persons with chronic
      disease are at risk for functional decline; as a result, there is an increased
      awareness of the significance of functional status as an important health
      outcome. The purpose of this study was to determine whether patients who receive
      a multi-component rehabilitation intervention, including online monitoring of
      function with feedback and self-management workshops, showed less functional
      decline than case matched controls who did not receive this intervention. In
      addition, we wanted to determine whether capacity building initiatives within the
      Family Health Team promote a collaborative approach to Chronic Disease
      Management. METHODS: A population-based multi-component rehabilitation
      intervention delivered to persons with chronic illnesses (>= 44 yrs) (n = 60) was
      compared to a group of age and sex matched controls (n = 60) with chronic
      illnesses receiving usual care within a primary healthcare setting. The
      population-based intervention consisted of four main components: (1) function
      based individual assessment and action planning, (2) rehabilitation self
      management workshops, (3) on-line self-assessment of function and (4)
      organizational capacity building. T-tests and chi-square tests were used for
      continuous and categorical variables respectively in baseline comparison between
      groups. RESULTS: Two MANOVA showed significant between group differences in
      patient reported physical functioning (Lambda = 0.88, F = (2.86) = 5.97. p =
      0.004) and for the physical performance measures collectively as the dependent
      variable (Lambda = 0.80, F = (6.93) = 3.68. p = 0.0025). There were no within
      group differences for the capacity measures. CONCLUSION: It is feasible to
      monitor physical functioning as a health outcome for persons with chronic illness
      in primary care. The timeline for this study was not sufficient to show an
      increase in the capacity within the team; however there were some differences in
      patient outcomes. The short timeline was likely not sufficient to build the
      capacity required to support this approach. TRIAL REGISTRATION: NCT00859638.

PMID- 22471379
TI  - Effect of different disinfectants on the microhardness and roughness of acrylic
      resins for ocular prosthesis.
AB  - BACKGROUND: Ocular prosthesis materials should have specific properties for their
      indication and durability; therefore, it is important to investigate their
      physical behaviour when affected by several disinfectants. OBJECTIVES: This study
      evaluated the influence of different disinfecting solutions on the microhardness
      and surface roughness of acrylic resins for ocular prosthesis. MATERIALS AND
      METHODS: Fifty samples simulating ocular prostheses were fabricated with N1 resin
      and colourless resin and divided (n = 10) according to the disinfectant used:
      neutral soap, Opti-free, Efferdent, 1% hypochlorite (HYC) and 4% chlorhexidine
      (CHX). Samples were stored in saline solution at 37 degrees C and disinfected
      during 120 days. Both microhardness and roughness were investigated before, after
      60 days and 120 days of disinfection and storage. Microhardness was measured
      using a microhardner and the roughness with a roughness device. RESULTS: N1 resin
      showed lower microhardness when compared with colourless resin (p < 0.05). HYC
      and CHX groups exhibited the highest change of microhardness and roughness values
      (p < 0.05). An increase in roughness and reduction in microhardness of ocular
      acrylic resins were observed after both periods of disinfection and storage (p <
      0.05). CONCLUSION: Both disinfection/storage periods affected the microhardness
      and roughness values of the samples.

PMID- 22471380
TI  - Stopping the revolving door: a meta-analysis on the effectiveness of
      interventions for criminally involved individuals with major mental disorders.
AB  - Faced with high and increasing rates of mental disorder within the criminal
      justice system (CJS), a range of interventions have been implemented in an effort
      to prevent continued involvement in criminal activities among this population. A
      meta-analytic review was undertaken to consider the effectiveness of
      interventions for criminally involved adults with a mental disorder targeting
      either improved criminal justice or mental health outcomes. Furthermore,
      characteristics that were hypothesized to predict better outcomes were examined.
      Studies that considered sex offender interventions, or focused solely on
      antisocial personality, intellectual and cognitive, or substance use disorders
      were excluded. Results assuming a fixed-effects model combining 37 effect sizes
      from 25 studies (N = 15,678) support the effectiveness of these interventions in
      terms of reductions in any CJS involvement (d = 0.19 excluding one outlier).
      Interventions had no significant effect on an aggregate mental health outcome (d
      = 0.00). However, when considering distinct mental health outcomes, intervention
      participants had significantly better functioning (d = 0.20) and fewer symptoms
      (d = 0.12). There were no significant effects of the interventions on mental
      health service or medication use. Moderator analyses identified seven sample,
      intervention, and design characteristics that were related to the magnitude of
      the effect sizes for criminal justice outcomes, and suggest implications for
      service provision, policy, and research. Results suggested some relationship
      between intervention effects on mental health and criminal justice reinvolvement,
      although future research is needed in this area, especially given the absence of
      mental health outcome data in many studies.

PMID- 22471381
TI  - Temporal discounting: the differential effect of proximal and distal consequences
      on confession decisions.
AB  - Drawing on the psychological principle that proximal consequences influence
      behavior more strongly than distal consequences, the authors tested the
      hypothesis that criminal suspects exhibit a short-sightedness during police
      interrogation that increases their risk for confession. Consistent with this
      hypothesis, Experiment 1 showed that participants (N = 81) altered how frequently
      they admitted to criminal and unethical behaviors during an interview to avoid a
      proximal consequence even though doing so increased their risk of incurring a
      distal consequence. Experiment 2 (N = 143) yielded the same pattern, but with a
      procedure that reversed the order of the proximal and distal consequences,
      thereby ruling out the possibility that it was the unique characteristics of the
      consequences rather than their proximity that influenced the admission rate. The
      authors discuss the supported psychological process as a potential explanation
      for several well-established findings reported in the literature on confessions.

PMID- 22471382
TI  - The impact of juveniles' ages and levels of psychosocial maturity on judges'
      opinions about adjudicative competence.
AB  - This study investigated whether defendants' ages and levels of psychosocial
      maturity would affect judges' ratings of juveniles' adjudicative competence in
      juvenile and criminal court. Three hundred forty two judges reviewed a forensic
      psychological report about a hypothetical defendant; only the defendant's age (12
      17) and maturity level (mature, immature) varied across reports. Results revealed
      a main effect of age, with older juveniles generally deemed more competent, and a
      main effect of maturity, with mature juveniles generally deemed more competent.
      No interaction was found. Results suggest that age and maturity play major roles
      in judicial determinations of juvenile competency.

PMID- 22471383
TI  - Improving eyewitness identification accuracy by screening out those who say they
      don't know.
AB  - Improving eyewitness identification evidence remains a key priority for research.
      Basic laboratory research has consistently demonstrated that allowing
      participants to withhold answers about which they are unsure leads to improved
      accuracy. Surprisingly, this approach has not been the subject of comprehensive
      investigation in the eyewitness identification literature. In this article, we
      explored the utility of allowing uncertain witnesses to opt out of an
      identification decision, by providing an explicit don't know option. Further, we
      contrasted the rate of use of this explicit option with the frequency that
      participants spontaneously withheld a decision when asked to respond in their own
      words. Four hundred and twenty participants witnessed a mock crime video before
      being presented with a showup of the perpetrator or an innocent suspect.
      Participants were tested either immediately or after a 3-week delay, with one of
      the three report options: Participants either made their choice in their own
      words (spontaneous report), chose between identifying and rejecting the showup
      (forced-report), or chose between identification, rejection and don't know (free
      report). Only 2.2% of witnesses spontaneously used a don't know response,
      compared to 19.3% who used it when the option was explicit. Compared with the
      forced-report decisions, free-report decisions were more accurate, more
      diagnostic of the suspect's guilt or innocence, and came at no cost to the number
      of correct decisions rendered. These data suggest that utilisation of an explicit
      don't know option may be of practical value.

PMID- 22471384
TI  - Treating offenders with mental illness: a research synthesis.
AB  - The purpose of this research synthesis was to examine treatment effects across
      studies of the service providers to offenders with mental illness. Meta-analytic
      techniques were applied to 26 empirical studies obtained from a review of 12,154
      research documents. Outcomes of interest in this review included measures of both
      psychiatric and criminal functioning. Although meta-analytic results are based on
      a small sample of available studies, results suggest interventions with offenders
      with mental illness effectively reduced symptoms of distress, improving
      offender's ability to cope with their problems, and resulted in improved
      behavioral markers including institutional adjustment and behavioral functioning.
      Furthermore, interventions specifically designed to meet the psychiatric and
      criminal justice needs of offenders with mental illness have shown to produce
      significant reductions in psychiatric and criminal recidivism. Finally, this
      review highlighted admission policies and treatment strategies (e.g., use of
      homework), which produced the most positive benefits. Results of this research
      synthesis are directly relevant for service providers in both criminal justice
      and mental health systems (e.g., psychiatric hospitals) as well as community
      settings by informing treatment strategies for the first time, which are based on
      empirical evidence. In addition, the implications of these results to policy
      makers tasked with the responsibility of designating services for this special
      needs population are highlighted.

PMID- 22471385
TI  - Crocodile tears: facial, verbal and body language behaviours associated with
      genuine and fabricated remorse.
AB  - Emotional deception is a common behaviour that can have major consequences if
      undetected. For example, the sincerity of an offender's expressed remorse is an
      important factor in sentencing and parole hearings. The present study was the
      first to investigate the nature of true and false remorse. We examined facial,
      verbal and body language behaviours associated with emotional deception in
      videotaped accounts of true personal transgressions accompanied by either genuine
      or falsified remorse. Analyses of nearly 300,000 frames indicated that
      descriptions of falsified remorse were associated with a greater range of
      emotional expressions. Further, sequential analyses revealed that negative
      emotions were more commonly followed by other emotions-rather than a return to
      neutral emotion-in falsified versus sincere remorse. Participants also exhibited
      more speech hesitations while expressing deceptive relative to genuine remorse.
      In general, the results suggest that falsified remorse may be conceived as an
      emotionally turbulent display of deliberate, falsified expressions and
      involuntary, genuine, emotional leakage. These findings are relevant to judges
      and parole board members who consider genuine remorse to be an important factor
      in sentencing and release decisions.

PMID- 22471386
TI  - Assessment and management of risk for intimate partner violence by police
      officers using the Spousal Assault Risk Assessment Guide.
AB  - Intimate partner violence (IPV) is a crime that is present in all countries,
      seriously impacts victims, and demands a great deal of time and resources from
      the criminal justice system. The current study examined the use of the Spousal
      Assault Risk Assessment Guide, 2nd ed. (SARA; Kropp, Hart, Webster, & Eaves,
      1995), a structured professional judgment risk assessment and management tool for
      IPV, by police officers in Sweden over a follow-up of 18 months. SARA risk
      assessments had significant predictive validity with respect to risk management
      recommendations made by police, as well as with recidivism as indexed by
      subsequent contacts with police. Risk management mediated the association between
      risk assessment and recidivism: High levels of intervention were associated with
      decreased recidivism in high risk cases, but with increased recidivism in low
      risk cases. The findings support the potential utility of police-based risk
      assessment and management of IPV, and in particular the belief that appropriately
      structured risk assessment and management decisions can prevent violence.

PMID- 22471387
TI  - Does the truth come out in the writing? Scan as a lie detection tool.
AB  - We tested the accuracy of Scientific Content Analysis (SCAN), a verbal lie
      detection tool that is used world-wide by federal law enforcement and military
      agencies. Sixty-one participants were requested to write down the truth, an
      outright lie or a concealment lie about activities they had just completed. The
      statements were coded with SCAN and with another verbal lie detection tool,
      Reality Monitoring (RM). RM discriminated significantly between truth tellers and
      outright liars and between truth tellers and concealment liars, whereas SCAN did
      not discriminate between truth tellers and either kind of liar. Implications of
      the findings for the suitability of SCAN as a lie detection tool are discussed.

PMID- 22471388
TI  - Altered expression of cytokine signaling pathway genes in peripheral blood cells
      of alcohol dependent subjects: preliminary findings.
AB  - BACKGROUND: Preclinical and clinical studies have implicated changes in cytokine
      and innate immune gene-expression in both the development of and end-organ damage
      resulting from alcohol dependence. However, these changes have not been
      systematically assessed on the basis of alcohol consumption in human subjects.
      METHODS: Illumina Sentrix Beadchip (Human-6v2) microarrays were used to measure
      levels of gene-expression in peripheral blood in 3 groups of subjects: those with
      alcohol dependence (AD, n = 12), heavy drinkers (HD; defined as regular alcohol
      use over the past year of at least 8 standard drinks/wk for women and at least 15
      standard drinks/wk for men, n = 13), and moderate drinkers (MD; defined as up to
      7 standard drinks/wk for women and 14 standard drinks/wk for men, n = 17).
      RESULTS: Four hundred and thirty-six genes were differentially expressed among
      the 3 groups of subjects (false discovery rate corrected p-value < 0.05). Two
      hundred and ninety-one genes differed between AD and MD subjects, 240 differed
      between AD and HD subjects, but only 6 differed between HD and MD subjects.
      Pathway analysis using DAVID and GeneGO Metacore((r)) software showed that the
      most affected pathways were those related to T-cell receptor and Janus kinase
      Signal transducer and activator of transcription (JAK-Stat) signaling.
      CONCLUSIONS: These results suggest the transition from heavy alcohol use to
      dependence is accompanied by changes in the expression of genes involved in
      regulation of the innate immune response. Such changes may underlie some of the
      previously described changes in immune function associated with chronic alcohol
      abuse. Early detection of these changes may allow individuals at high risk for
      dependence to be identified.

PMID- 22471390
TI  - Coinheritance of Hb S [beta6(A3)Glu->Val, GAG>GTG] with beta0-thalassemia codon
      17 (A>T) in a Thai patient.
AB  - Hb S [beta6(A3)Glu->Val, GAG>GTG] is a beta-globin gene variant that has a very
      low incidence in the Thai population. Coinheritance of Hb S and beta(0)
      thalassemia (beta-thal) can result in severe clinical conditions. This study
      reports the case of a Thai patient with a compound heterozygosity for Hb S and
      beta(0)-thal codon 17 (A>T). His hemoglobin (Hb), hematocrit (packed cell volume,
      PCV), mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) levels were all
      less than the lower limits, while red cell distribution width (RDW) was higher
      than the upper limit. Levels of Hbs S, F and A(2) detected by high performance
      liquid chromatography (HPLC) were comparable to those from capillary
      electrophoresis (CE). As Hb S has a similar electrophoretic mobility and the HPLC
      profile is also similar to those of Hb Tak [beta147, Term->Thr (+AC)] and Hb D
      Punjab [beta121(GH4)Glu->Gln, GAA>CAA], DNA sequencing was then performed. This
      was to detect beta(0)-thal, and to differentiate Hb S from the Hb Tak and Hb D
      Punjab mutations. The beta(0)-thal codon 17 and Hb S mutations were detected
      indicating that coinheritance of these two mutations can be found in the Thai
      population. Therefore, to provide proper clinical management and genetic
      counseling of this rare case, DNA analysis should be performed in all cases when
      a peak at the S-window is detected by HPLC or CE.

PMID- 22471389
TI  - Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling
      pathway in 3T3-L1 cells.
AB  - BACKGROUND: Obesity is a health hazard that is associated with a number of
      diseases and metabolic abnormalities, such as type-2 diabetes, hypertension,
      dyslipidemia, and coronary heart disease. In the current study, we investigated
      the effects of Citrus aurantium flavonoids (CAF) on the inhibition of
      adipogenesis and adipocyte differentiation in 3T3-L1 cells. METHODS: During
      adipocyte differentiation, 3T3-L1 cells were treated with 0, 10, and 50 MUg/ml
      CAF, and then the mRNA and protein expression of adipogenesis-related genes was
      assayed. We examined the effect of CAF on level of phosphorylated Akt in 3T3-L1
      cells treated with CAF at various concentrations during adipocyte
      differentiation. RESULTS: The insulin-induced expression of C/EBPbeta and
      PPARgamma mRNA and protein were significantly down-regulated in a dose-dependent
      manner following CAF treatment. CAF also dramatically decreased the expression of
      C/EBPalpha, which is essential for the acquisition of insulin sensitivity by
      adipocytes. Moreover, the expression of the aP2 and FAS genes, which are involved
      in lipid metabolism, decreased dramatically upon treatment with CAF.
      Interestingly, CAF diminished the insulin-stimulated serine phosphorylation of
      Akt (Ser473) and GSK3beta (Ser9), which may reduce glucose uptake in response to
      insulin and lipid accumulation. Furthermore, CAF not only inhibited triglyceride
      accumulation during adipogenesis but also contributed to the lipolysis of
      adipocytes. CONCLUSIONS: In the present study, we demonstrate that CAF suppressed
      adipogenesis in 3T3-L1 adipocytes. Our results indicated that CAF down-regulates
      the expression of C/EBPbeta and subsequently inhibits the activation of PPARgamma
      and C/EBPalpha. The anti-adipogenic activity of CAF was mediated by the
      inhibition of Akt activation and GSK3beta phosphorylation, which induced the down
      regulation of lipid accumulation and lipid metabolizing genes, ultimately
      inhibiting adipocyte differentiation.

PMID- 22471391
TI  - Successful transplantation of rat hearts subjected to extended cold preservation
      with a novel preservation solution.
AB  - Since prolonged cold preservation of the heart deteriorates the outcome of heart
      transplantation, a more protective preservation solution is required. We
      therefore developed a new solution, named Dsol, and examined whether Dsol, in
      comparison to UW, could better inhibit myocardial injury resulting from prolonged
      cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was
      performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to
      graft survival, myocardial injury, ATP content, and Ca(2+) -dependent proteases
      activity were assessed in the 24-h preservation group. The cytosolic Ca(2+)
      concentration of H9c2 cardiomyocytes after 24-h cold preservation was assessed.
      Dsol significantly improved 7-day graft survival after 36-h preservation. After
      24-h preservation, Dsol was associated with significantly faster recovery of ATP
      content and less activation of calpain and caspase-3 after reperfusion. Dsol
      diminished graft injury significantly, as revealed by the lower levels of
      infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day.
      Dsol significantly inhibited Ca(2+) overload during cold preservation. Dsol
      inhibited myocardial injury and improved graft survival by suppressing Ca(2+)
      overload during the preservation and the activation of Ca(2+) -dependent
      proteases. Dsol is therefore considered a better alternative to UW to ameliorate
      the outcome of heart transplantation.

PMID- 22471392
TI  - Effects of atenolol, perindopril and verapamil on haemodynamic and vascular
      function in Marfan syndrome - a randomised, double-blind, crossover trial.
AB  - BACKGROUND: Aortic dilatation is the main therapeutic target in patients with
      Marfan syndrome. Standard treatment with a beta-blocker may not lower central
      pulse pressure - the major objective - because it does not do so in hypertension,
      unlike angiotensin-converting enzyme inhibitors and calcium-channel blockers. We
      therefore performed a prospective, randomised, double-blind, crossover trial to
      compare the effects of these three agents on large artery function and central
      aortic pressure in patients with Marfan syndrome. METHODS AND RESULTS: Eighteen
      patients had applanation tonometry, pulse wave analysis and echocardiography,
      before and after atenolol 75 mg, perindopril 4 mg and verapamil 240 mg, each
      given for 4 weeks, in a random order, with 2 weeks between medications. Fourteen
      patients completed the study. Within-drug comparisons demonstrated that
      perindopril (-10.3 mmHg, P = 0.002), verapamil (-9.2 mmHg, P = 0.003) and
      atenolol (-7.1 mmHg, P = 0.01) all reduced central systolic pressure and brachial
      pressure; central changes were least, and peripheral changes greatest with
      atenolol but between-drug comparisons (analysis of covariance) were not
      significant. There was a trend for augmentation to be reduced by perindopril (
      6.3%, P = 0.05), verapamil (-5.5%, P = 0.07) and atenolol (-3.2%, P = 0.09). Only
      atenolol reduced heart rate (by 16%) and delayed expansion in the arch and
      abdominal aorta (by 8% and 11%) (P < 0.001, P < 0.01 and P < 0.05, respectively,
      for between-drug comparisons). CONCLUSIONS: Perindopril, verapamil and atenolol
      all reduced peripheral and central systolic pressure. As atenolol slowed heart
      rate and delayed aortic wave travel, beta-blockade may have a continuing role in
      the treatment of patients with Marfan syndrome.

PMID- 22471394
TI  - Identification of functionally relevant populations in enhanced biological
      phosphorus removal processes based on intracellular polymers profiles and
      insights into the metabolic diversity and heterogeneity.
AB  - This study proposed and demonstrated the application of a new Raman microscopy
      based method for metabolic state-based identification and quantification of
      functionally relevant populations, namely polyphosphate accumulating organisms
      (PAOs) and glycogen accumulating organisms (GAOs), in enhanced biological
      phosphorus removal (EBPR) system via simultaneous detection of multiple
      intracellular polymers including polyphosphate (polyP), glycogen, and
      polyhydroxybutyrate (PHB). The unique Raman spectrum of different combinations of
      intracellular polymers within a cell at a given stage of the EBPR cycle allowed
      for its identification as PAO, GAO, or neither. The abundance of total PAOs and
      GAOs determined by Raman method were consistent with those obtained with polyP
      staining and fluorescence in situ hybridization (FISH). Different combinations
      and quantities of intracellular polymer inclusions observed in single cells
      revealed the distribution of different sub-PAOs groups among the total PAO
      populations, which exhibit phenotypic and metabolic heterogeneity and diversity.
      These results also provided evidence for the hypothesis that different PAOs may
      employ different extents of combination of glycolysis and TCA cycle pathways for
      anaerobic reducing power and energy generation and it is possible that some PAOs
      may rely on TCA cycle solely without glycolysis. Sum of cellular level
      quantification of the internal polymers associated with different population
      groups showed differentiated and distributed trends of glycogen and PHB level
      between PAOs and GAOs, which could not be elucidated before with conventional
      bulk measurements of EBPR mixed cultures.

PMID- 22471393
TI  - Functional neuroimaging of treatment effects in psychiatry: methodological
      challenges and recommendations.
AB  - Functional magnetic resonance imaging (fMRI) has helped to elucidate the
      neurobiological bases of psychiatric and neurodevelopmental disorders by
      localizing etiologically-relevant aberrations in brain function. Functional MRI
      also has shown great promise to help understand potential mechanisms of action of
      effective treatments for a range of psychiatric and neurodevelopmental disorders,
      including mood and anxiety disorders, schizophrenia, and autism. However, the use
      of fMRI to probe intervention effects in psychiatry is associated with unique
      methodological considerations, including the psychometric properties of repeated
      fMRI scans, how to assess potential relations between the effects of an
      intervention on symptoms and on specific brain activation patterns, and how to
      best make causal inferences about intervention effects on brain function.
      Additionally, the study of treatment effects in neurodevelopmental disorders
      presents additional unique challenges related to brain maturation, analysis
      methods, and the potential for motion artifacts. We review these methodological
      considerations and provide recommendations for best practices for each of these
      topics.

PMID- 22471395
TI  - Altered monocyte activation markers in Tourette's syndrome: a case-control study.
AB  - BACKGROUND: Infections and immunological processes are likely to be involved in
      the pathogenesis of Tourette's syndrome (TS). To determine possible common
      underlying immunological mechanisms, we focused on innate immunity and studied
      markers of inflammation, monocytes, and monocyte-derived cytokines. METHODS: In a
      cross-sectional study, we used current methods to determine the number of
      monocytes and levels of C-reactive protein (CRP) in 46 children, adolescents, and
      adult patients suffering from TS and in 43 healthy controls matched for age and
      sex. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble CD14
      (sCD14), IL1-receptor antagonist (IL1-ra), and serum neopterin were detected by
      immunoassays. RESULTS: We found that CRP and neopterin levels and the number of
      monocytes were significantly higher in TS patients than in healthy controls.
      Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in
      TS patients. All measured values were within normal ranges and often close to
      detection limits. CONCLUSIONS: The present results point to a monocyte
      dysregulation in TS. This possible dysbalance in innate immunity could predispose
      to infections or autoimmune reactions.

PMID- 22471396
TI  - Derivation of mean-square displacements for protein dynamics from elastic
      incoherent neutron scattering.
AB  - The derivation of mean-square displacements from elastic incoherent neutron
      scattering (EINS) of proteins is examined, with the aid of experiments on camphor
      bound cytochrome P450cam and complementary molecular dynamics simulations. It is
      shown that a q(4) correction to the elastic incoherent structure factor (where q
      is the scattering vector) can be simply used to reliably estimate from the
      experiment both the average mean-square atomic displacement, <Deltar(2)> of the
      nonexchanged hydrogen atoms in the protein and its variance, sigma(2). The
      molecular dynamics simulation results are in broad agreement with the
      experimentally derived <Deltar(2)> and sigma(2) derived from EINS on instruments
      at two different energy resolutions, corresponding to dynamics on the ~100 ps and
      ~1 ns time scales. Significant dynamical heterogeneity is found to arise from
      methyl-group rotations. The easy-to-apply q(4) correction extends the information
      extracted from elastic incoherent neutron scattering experiments and should be of
      wide applicability.

PMID- 22471399
TI  - Romiplostim therapy in children with unresponsive chronic immune
      thrombocytopenia.
AB  - Romiplostim, a thrombopoiesis-stimulating peptibody, represents a new therapeutic
      option in adult refractory chronic immune thrombocytopenia (ITP). This study
      aimed to assess the short-term efficacy and safety of romiplostim in children
      with chronic ITP. Eight non-splenectomized patients with chronic ITP refractory
      to standard lines of medical therapy were recruited from the Pediatric Hematology
      Unit, Children's Hospital, Ain Shams University, Cairo, Egypt. One patient was
      initially excluded because of increased bone marrow reticulin (grade 3). Therapy
      was initiated in seven patients, aged 3.4-15.2 years (median 5.5 years), and the
      disease duration ranged from 13 months to 7.3 years (median 2.4 years); none were
      splenectomized. Romiplostim dose was started as 1 ugm/kg/week and the dose
      escalated by 1 ugm/kg/week according to platelet count. The duration of therapy
      varied between 1 and 22 weeks (median 12 weeks). Results revealed that four out
      of the seven patients achieved variable response. Four patients demonstrated
      rapid increase in platelet count when pulse steroid therapy was added. Most
      reported adverse events were mild and transient. This case series study reveals
      variable response rate in children with chronic ITP to romiplostim therapy;
      addition of steroids especially in emergency bleeding situations could potentiate
      romiplostim thrombopoietic effect even in patients initially refractory to
      steroids. Romiplostim safety and efficacy in pediatric ITP needs further long
      term studies.

PMID- 22471400
TI  - Nanomolar concentrations of adrenaline induce platelet adhesion in vitro.
AB  - Adrenaline is a platelet activator having a resting plasma concentration of <1
      nmol/l that increases to a few nmol/l during stress. However, most in vitro
      assays only detect effects of adrenaline in micromolar concentrations. This makes
      it difficult to estimate the relevance of in vitro data for the in vivo
      situation. The aim of this study was to investigate experimental conditions in
      vitro that could detect platelet effects of adrenaline in nanomolar
      concentrations. Platelet adhesion to albumin and collagen was evaluated with a
      static platelet adhesion assay. Our results show that 10 nmol/l adrenaline
      induced platelet adhesion to albumin in platelet-rich plasma (PRP) prepared at
      140 * g, while 100 nmol/l was necessary in order to increase adhesion of
      platelets prepared at 220 * g. The mean platelet volume was increased after
      preparation at 140 * g, suggesting that large reactive platelets contributed to
      the increased adrenaline sensitivity. At optimal Mg(2+)-concentration, adhesion
      to collagen was increased by 10 nmol/l adrenaline irrespective of centrifugal
      force applied during PRP preparation. More specifically, we defined two
      populations where adhesion to collagen was increased by 10 nmol/l adrenaline
      either upon centrifugation at 140 * g but not 220 * g or vice versa. In some
      experiments, platelet adhesion to collagen was induced by 3 nmol/l adrenaline,
      which corresponds to concentrations achieved during stress in vivo. In summary,
      the static adhesion assay is able to detect platelet activating effects of
      adrenaline very close to physiological concentrations. This is rare for in vitro
      assays and motivates further research about adrenergic signalling in platelets.

PMID- 22471401
TI  - Ureteroscopic and percutaneous management of upper tract urothelial carcinoma
      (UTUC): systematic review.
AB  - What's known on the subject? and What does the study add? Endoscopic management
      of upper tract urothelial carcinoma (UTUC) using either ureteroscopy and laser
      ablation, or percutaneous resection, is a management option for treating selected
      low-grade tumours with favourable characteristics. However, the evidence base for
      such practice is relatively weak, as the reported experience is mainly limited to
      small case series (level of evidence 4), or non-randomised comparative studies
      that are unmatched for tumour stage (level of evidence 3b), with variability of
      follow-up duration and reported outcome measures. The present systematic review
      comprehensively reviews the outcomes of all studies of endoscopic management of
      UTUC, including the role of topical adjuvant therapy. It establishes for the
      first time a structured reference for endoscopic management of UTUC, and is a
      foundation for further clinical studies. OBJECTIVE: To systematically review the
      oncological outcomes of upper tract urothelial carcinoma (UTUC) treated with
      ureteroscopic and percutaneous management. The standard treatment of UTUC is
      radical nephroureterectomy (RNU). However, over the last two decades several
      institutions have treated UTUC endoscopically, either via ureteroscopic ablation
      or percutaneous nephroscopic resection of tumour (PNRT), for both imperative and
      elective indications. METHODS: For evidence acquisition the Pubmed database was
      searched for English language publications in December 2011 using the following
      terms: upper tract (UT) transitional cell carcinoma (TCC), upper tract TCC,
      UTTCC, upper tract urothelial cell carcinoma, upper tract urothelial carcinoma,
      UTUC, endoscopic management, ureteroscopic management, laser ablation,
      percutaneous management, PNRT, conservative management, ureteroscopic biopsy,
      biopsy, BCG, mitomycin C, topical therapy. RESULTS: There are no randomised
      trials comparing endoscopic management with RNU. Most published studies were
      retrospective case series (and database reviews), or unmatched comparative
      studies. There was strong selection bias for favourable tumour characteristics in
      many endoscopically treated groups. There was variation in medical comorbidity
      and indication for treatment across different study groups. The biopsy
      verification of underlying UTUC pathology was inconsistent. The follow-up in most
      studies was limited, typically to a mean 3 years. CONCLUSIONS: There is a high
      rate of UT recurrence with endoscopically managed UTUC, and a grade-related risk
      of tumour progression and disease-specific mortality. Overall, renal preservation
      may be high with ~20% of patients proceeding eventually to RNU. For highly
      selected Grade 1 (or low-grade) disease managed in experienced centres, 5-year
      disease-specific survival (DSS) may be equivalent to RNU, although the small
      study groups and short follow-ups preclude comments on less favourable Grade 1
      (or low-grade) tumour characteristics, or DSS, in the longer-term. For Grade 3
      (or high-grade) disease, DSS outcomes are poor and endoscopic management should
      only be considered for compelling imperative indications in the context of the
      patient's overall life expectancy and competing comorbidity.

PMID- 22471402
TI  - Interaction of cisplatin with human superoxide dismutase.
AB  - cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human
      superoxide dismutase (hSOD1) in the disulfide oxidized apo form with a
      dissociation constant of 37 +/- 3 MUM through binding cysteine 111 (Cys111)
      located at the edge of the subunit interface. It also binds to Cu(2)-Zn(2) and
      Zn(2)-Zn(2) forms of hSOD1. Cisplatin inhibits aggregation of demetalated
      oxidized hSOD1, and it is further able to dissolve and monomerize oxidized hSOD1
      oligomers in vitro and in cell, thus indicating its potential as a leading
      compound for amyotrophic lateral sclerosis.

PMID- 22471403
TI  - Preparation of Super-Stable Gold Nanorods via Encapsulation into Block Copolymer
      Micelles.
AB  - Gold nanorods (GNRs) have the potential to be used as imaging and hyperthermia
      agents for cancer theranostics. Clinical applications of as-synthesized GNRs
      (i.e., cetyl trimethylammonium bromide (CTAB)-coated GNRs) are currently limited
      by their cytotoxicity and insufficient colloidal stability. With an aim to
      address these problems, we developed a self-assembly processing technique for
      encapsulating GNRs in poly(ethylene oxide)-poly(n-butyl acrylate) (PEO-PnBA)
      block copolymer (BCP) micelles. This technique uses simple steps of solvent
      exchange processes, based on the known principles of block copolymer self
      assembly. The resultant BCP-encapsulated GNRs were found to be stable against
      aggregation under physiological salt conditions for indefinite periods of time,
      which has rarely previously been achieved by other means of encapsulation.

PMID- 22471404
TI  - Survival rates after diabetic vitrectomy compared with standard diabetes and
      general populations.

PMID- 22471405
TI  - Diversity and evolution of ectomycorrhizal host associations in the
      Sclerodermatineae (Boletales, Basidiomycota).
AB  - This study uses phylogenetic analysis of the Sclerodermatineae to reconstruct the
      evolution of ectomycorrhizal host associations in the group using divergence
      dating, ancestral range and ancestral state reconstructions. Supermatrix and
      supertree analysis were used to create the most inclusive phylogeny for the
      Sclerodermatineae. Divergence dates were estimated in BEAST. Lagrange was used to
      reconstruct ancestral ranges. BayesTraits was used to reconstruct ectomycorrhizal
      host associations using extant host associations with data derived from
      literature sources. The supermatrix data set was combined with internal
      transcribed spacer (ITS) data sets for Astraeus, Calostoma, and Pisolithus to
      produce a 168 operational taxonomic unit (OTU) supertree. The ensuing analysis
      estimated that basal Sclerodermatineae originated in the late Cretaceous while
      major genera diversified near the mid Cenozoic. Asia and North America are the
      most probable ancestral areas for all Sclerodermatineae, and angiosperms,
      primarily rosids, are the most probable ancestral hosts. Evolution in the
      Sclerodermatineae follows the biogeographic history of disjunct plant communities
      associated with early Cenozoic mesophytic forests and a boreotropical history.
      Broad geographic distributions are observed in the most promiscuous
      Sclerodermatineae (those with broad host ranges), while those with relatively
      limited distribution have fewer documented ectomycorrhizal associations. This
      suggests that ectomycorrhizal generalists have greater dispersal capabilities
      than specialists.

PMID- 22471406
TI  - Diminished pheromone-induced sexual behavior in neurokinin-1 receptor deficient
      (TACR1(-/-)) mice.
AB  - Studies in mice with targeted deletions of tachykinin genes suggest that
      tachykinins and their receptors influence emotional behaviors such as aggression,
      depression and anxiety. Here, we investigated whether TAC1- and TAC4-encoded
      peptides (substance P and hemokinin-1, respectively) and the neurokinin-1
      receptor (NK-1R) are involved in the modulation of sexual behaviors. Male mice
      deficient for the NK-1R (TACR1 (-/-)) exhibited decreased exploration of female
      urine in contrast to C57BL/6 control mice and mice deficient for NK-1R ligands
      such as TAC1 (-/-), TAC4 (-/-) and the newly generated TAC1 (-/-) /TAC4 (-/-)
      mice. In comparison to C57BL/6 mice, mounting frequency and duration were
      decreased in male TACR1 (-/-) mice, while mounting latency was increased.
      Decreased preference for sexual pheromones was also seen in female TACR1 (-/-)
      mice. Furthermore, administration of the NK-1R-antagonist L-703,606 decreased
      investigation of female urine by male C57BL/6 mice, suggesting an involvement of
      NK-1R in urine sniffing behavior. Our results provide evidence for the NK-1R in
      facilitating sexual approach behavior, as male TACR1 (-/-) mice exhibited blunted
      approach behavior toward females following the initial interaction compared with
      C57BL/6 mice. NK-1R signaling may therefore play an important role in pheromone
      induced sexual behavior.

PMID- 22471407
TI  - Modified flap design for symmetric reconstruction of the apical triangle of the
      upper lip.
AB  - BACKGROUND: The apical triangle is the superior portion of the cutaneous upper
      lip lying between the medial cheek and alar margin. Defects involving this
      subunit are often repaired without taking into consideration the aesthetic
      implications of its potential loss or reduction. We present a simple option for
      repair of apical triangle defects to address this concern. METHODS: We collected
      a series of 69 patients with apical triangle defects treated from 2002 to 2008
      with Mohs micrographic surgery. Their defects were reconstructed using various
      flaps (advancement, rotation, island pedicle, or M-plasty). A subset of 27
      patients was identified who had undergone a standard cheek advancement flap or a
      modified flap. The modified design introduces an incision extending from the alar
      crease onto the nasal sill along the cutaneous upper lip, creating a second
      sliding flap to assist in recreating the apical triangle. RESULTS: A modified
      flap design introduced the ability to transfer adjacent tissue of the cutaneous
      upper lip to reconstruct the apical triangle subunit. CONCLUSION: This flap
      modification is a simple and efficient method of repairing peri-alar defects that
      restores the apical subunit, preserving facial symmetry.

PMID- 22471408
TI  - Quality of services and quality of life from service providers' perspectives:
      analysis with focus groups.
AB  - BACKGROUND: Concepts such as support, quality of life and quality of services are
      customary in services for people with intellectual disabilities. The
      identification of the different ways of conceiving, prioritising and implementing
      these concepts by service providers can help to drive changes to achieve better
      personal outcomes for this population. The current study aims to identify service
      providers' perceptions regarding the quality of life of their clients and the
      quality of services they provide. It also aims to identify similarities and
      differences of appraisals among professionals, and to identify associations
      between supports, quality of life and quality of services. METHOD: Data were
      collected from 22 service providers who attended three focus groups
      (professionals, direct support staff, and managers) from whom 424 comments were
      analysed. Service providers were asked about the required support for users, the
      meaning of quality of life for those users, and about features that should
      characterise quality services. Thematic analysis was employed and transcripts of
      the sessions were coded according to the dimensions of models on supports,
      quality of life and quality of services. Chi-squared tests were utilised to test
      for potential differences among groups. RESULTS: Each professional group has its
      own priorities concerning required supports. Among the organisation different and
      potentially conflicting perceptions regarding the meaning of experiencing quality
      of life coexist. Concerning quality of services, only managers mentioned personal
      outcomes. Finally, institutionalisation has a negative impact on supports,
      quality of life and quality of services. CONCLUSIONS: It is necessary to move
      beyond a shared awareness of the negative impact of institutionalisation towards
      the transformation of services in search of personal quality outcomes.

PMID- 22471409
TI  - Validity and reliability of a visual scoring method for masticatory ability using
      test gummy jelly.
AB  - BACKGROUND: For quantitative evaluation of masticatory ability of the elderly
      patients, there should be a simple and reliable method without special techniques
      and instruments. OBJECTIVE: The purpose of this study was to examine the validity
      and reliability of a visual scoring method for assessing masticatory performance.
      MATERIALS AND METHODS: A 10-stage scale for visually scoring was rated based on
      the range of the glucose concentration dissolved from comminuted jelly.
      Photographic images of comminuted jellies were produced as a standard material
      for each score. Fifty subjects were recruited as raters who graded the visual
      score for 50 photographic images of comminuted jellies on the screen of a lap-top
      three times in random order. RESULTS: There were strong correlations (rs = 0.911-
      0.981, Spearman's rank coefficient) between the actual scores determined from the
      glucose concentration and the visual scores graded by subjects in all three
      measurements. The intraclass correlation coefficients (ICCs) of the inter-rater
      reliability and the ICCs of the intra-rater reliability of the visual scoring
      ranged from 0.946 to 0.947 and from 0.860 to 0.987 in three measurements,
      respectively. CONCLUSIONS: These results indicated that the visual scoring method
      was valid and reliable for evaluation of masticatory performance.

PMID- 22471410
TI  - Epidemiological and clinical features of human rabies cases in Bali 2008-2010.
AB  - BACKGROUND: Previously thought to be rabies free, Bali experienced an outbreak of
      animal and human rabies cases in November 2008. We describe the epidemiological
      and clinical data of human rabies cases occurring in the first two years of the
      outbreak. METHODS: We analysed the patient records of all rabies cases from the
      Sanglah General Hospital in Denpasar, and district hospitals in Buleleng and
      Tabanan. A conventional reverse transcriptase polymerase chain reaction was
      developed to detect the rabies virus genome in saliva, corneal swabs, and ante-
      and post-mortem cerebrospinal fluid (CSF). RESULTS: There were 104 human rabies
      cases in Bali during November 2008-November 2010. Patients' mean age was 36.6
      years (range 3-84 years; SD 20.7), most were male (56.7%), and originated from
      rural districts. Almost all (92%) cases had a history of dog bite. Only 5.8% had
      their wounds treated and received an anti-rabies vaccine (ARV) after the bite
      incident. No patients received rabies immunoglobulin (RIG). The estimated time
      from dog bite to the onset of signs and symptoms was 110.4 days (range 12-720
      days; SD 118.2). The mean length of medical care until death was 21.8 hours
      (range 1-220 hours; SD 32.6). Less than 50% of patients had prodromal symptoms.
      The most frequent prodromal symptom was pain or paraesthesia at the bite site
      (37.6%). The two most common central nervous system infection signs were
      agitation (89.2%) and confusion (83.3%). Signs of autonomic nervous system
      dysfunction included hydrophobia (93.1%), hypersalivation (88.2%), and dyspnea
      (74.4%). On admission, 22 of 102 patients (21.6%) showed paralytic
      manifestations, while the rest (78.4%) showed furious rabies manifestations. The
      case-fatality rate was 100%. The rabies virus genome was detected in 50 of 101
      patients (49.5%) with the highest detection rate from post-mortem CSF samples.
      CONCLUSIONS: Rabies is a major public health problem in Bali. Human fatalities
      occur because of a lack of knowledge regarding rabies risk, the poor management
      of dog bites, and the limited availability of RIG. Increasing public awareness of
      dog bite management, increasing the availability of ARV and RIG, and implementing
      an island-wide dog vaccination campaign will help prevent human rabies cases.

PMID- 22471411
TI  - Mycobacterium avium complex--the role of potable water in disease transmission.
AB  - Mycobacterium avium complex (MAC) is a group of opportunistic pathogens of major
      public health concern. It is responsible for a wide spectrum of disease dependent
      on subspecies, route of infection and patients pre-existing conditions.
      Presently, there is limited research on the incidence of MAC infection that
      considers both pulmonary and other clinical manifestations. MAC has been isolated
      from various terrestrial and aquatic environments including natural waters,
      engineered water systems and soils. Identifying the specific environmental
      sources responsible for human infection is essential in minimizing disease
      prevalence. This paper reviews current literature and case studies regarding the
      wide spectrum of disease caused by MAC and the role of potable water in disease
      transmission. Potable water was recognized as a putative pathway for MAC
      infection. Contaminated potable water sources associated with human infection
      included warm water distribution systems, showers, faucets, household drinking
      water, swimming pools and hot tub spas. MAC can maintain long-term contamination
      of potable water sources through its high resistance to disinfectants,
      association with biofilms and intracellular parasitism of free-living protozoa.
      Further research is required to investigate the efficiency of water treatment
      processes against MAC and into construction and maintenance of warm water
      distribution systems and the role they play in MAC proliferation.

PMID- 22471412
TI  - Intoxicated eyewitnesses: Better than their reputation?
AB  - According to law enforcement, many witnesses are intoxicated either at the time
      of the crime, the interview, or both (Evans et al., Public Policy Law 15(3):194
      221, 2009). However, no study to date has examined whether intoxicated witnesses'
      recall is different from sober witnesses' and whether they are more vulnerable to
      misinformation using an ecologically valid experimental design. Intoxicated,
      placebo, and sober witnesses observed a live, staged theft, overheard subsequent
      misinformation about the theft, and took part in an investigative interview.
      Participants generally believed they witnessed a real crime and experienced a
      real interview. Intoxicated witnesses were not different from placebo or sober
      witnesses in the number of accurate details, inaccurate details, or "don't know"
      answers reported. All the participants demonstrated a misinformation effect, but
      there were no differences between intoxication levels: Intoxicated participants
      were not more susceptible to misinformation than sober or placebo participants.
      Results are discussed in the light of their theoretical and applied relevance.

PMID- 22471413
TI  - Mental health in violent crime victims: Does sexual orientation matter?
AB  - The present study investigates victim sexual orientation in a sample of 641
      violent crime victims seeking emergency medical treatment at a public-sector
      hospital. Victim sexual orientation was examined as it: (a) varies by type of
      violent crime and demographic characteristics, (b) directly relates to
      psychological symptoms, and (c) moderates the relationship between victim and
      crime characteristics (i.e., victim gender, victim trauma history, and type of
      crime) and psychological symptoms (i.e., symptoms of acute stress, depression,
      panic, and general anxiety). Results showed that lesbian, gay, bisexual, and
      transgender (LGBT) victims were more likely to be victims of sexual assault.
      Heterosexual victims were more likely to be victims of general assault and
      shootings. LGBT victims demonstrated significantly higher levels of acute stress
      and general anxiety. Moreover, victim sexual orientation moderated the
      association of type of crime with experience of panic symptoms. Also, victim
      sexual orientation moderated the relation of victim trauma history and general
      anxiety symptoms. Results are discussed in relation to victimization prevalence
      rates, sexual prejudice theory, and assessment and treatment of violent crime
      victims.

PMID- 22471414
TI  - Abstract principles and concrete cases in intuitive lawmaking.
AB  - Citizens awaiting jury service were asked a series of items, in Likert format, to
      determine their endorsement of various statements about principles to use in
      setting child support amounts. These twenty items were derived from extant child
      support systems, from past literature and from Ellman and Ellman's (2008) Theory
      of Child Support. The twenty items were found to coalesce into four factors
      (principles). There were pervasive gender differences in respondent's endorsement
      of the principles. More importantly, three of these four principles were
      systematically reflected, in very rational (if complex) ways, in the respondents'
      resolution of the individual child support cases they were asked to decide.
      Differences among respondents in their endorsement of these three principles
      accounted for differences in their patterns of child support judgments. It is
      suggested that the pattern of coherent arbitrariness (Ariely et al., Q J Econ
      118(1):73-105, 2003) in those support judgments, noted in an earlier study
      (Ellman, Braver, & MacCoun, 2009) is thus partially explained, in that the
      seeming arbitrariness of respondents' initial support judgments reflect in part
      their differing views about the basic principles that should decide the cases.

PMID- 22471415
TI  - Supervision practices in specialty mental health probation: What happens in
      officer-probationer meetings?
AB  - As the correctional population continues to increase, probation agencies struggle
      to adequately supervise offenders with unique needs, including those with mental
      disorder. Although more than 100 U.S. probation agencies have implemented
      specialty mental health case-loads, little is known about their practices. Based
      on detailed observations of 83 audio-taped meetings, we examined interactions
      between probationers and officers in a prototypic specialty agency, focusing on
      the extent to which practices comport with evidence-based risk reduction
      principles. We found that specialty officers (a) more frequently discussed
      probationers' general mental health than any individual criminogenic need, (b)
      chiefly questioned, directed, affirmed, and supported (rather than confronted)
      probationers, and (c) relied more heavily on neutral strategies and positive
      pressures (e.g., inducements) rather than negative pressures (e.g., threats of
      incarceration) to monitor and enforce compliance. Implications for "what works"
      to promote community integration for probationers with mental disorder are
      discussed.

PMID- 22471416
TI  - Family violence risk assessment: A predictive cross-validation study of the
      Domestic Violence Screening Instrument-Revised (DVSI-R).
AB  - This research was a cross-validation study of the Domestic Violence Screening
      Instrument-Revised (DVSI-R), using a diverse, statewide sample of 3,569 family
      violence perpetrators in Connecticut, assessed in February and March of 2007. It
      analyzed re-arrest data collected during an 18-month period post assessment.
      Three issues were central, which have been ignored in previous research on family
      violence risk assessment: (1) analyzing five refined measures of behavioral
      recidivism, (2) determining whether perpetrator characteristics and types of
      family and household relationships (beyond just heterosexual intimate partners)
      moderate the empirical relations between the DVSI-R and the behavioral recidivism
      measures, and (3) determining whether structured clinical judgment about the
      imminent risk of future violence to the victim or to others corresponds with
      recidivism predicted by the DVSI-R total numeric risk scores. The empirical
      findings showed that the DVSI-R had significant predictive accuracy across all
      five measures of recidivism. With one exception, these relations did not vary by
      gender, age, or ethnicity; and again with one exception, no significant evidence
      was found that types of family or household relationships moderated those
      empirical relations. In short, the evidence suggested that the DVSI-R was a
      robust risk assessment instrument, having applicability across different types of
      perpetrators and different types of family and household relationships. Finally,
      the empirical findings showed that structured clinical judgment about imminent
      risk-to-victim and risk-to-others corresponded with the prediction of recidivism
      by the DVSI-R total numeric risk scores, but the effects of those scores were
      significantly stronger than the perceived risk-to-victim or the perceived risk-to
      others.

PMID- 22471417
TI  - Field reliability of competence to stand trial opinions: How often do evaluators
      agree, and what do judges decide when evaluators disagree?
AB  - Despite many studies that examine the reliability of competence to stand trial
      (CST) evaluations, few shed light on "field reliability," or agreement among
      forensic evaluators in routine practice. We reviewed 216 cases from Hawaii, which
      requires three separate evaluations from independent clinicians for each felony
      defendant referred for CST evaluation. Results revealed moderate agreement. In
      71% of initial CST evaluations, all evaluators agreed about a defendant's
      competence or incompetence (kappa = .65). Agreement was somewhat lower (61%,
      kappa = .57) in re-evaluations of defendants who were originally found
      incompetent and sent for restoration services. We also examined the decisions
      judges made about a defendant's CST. When evaluators disagreed, judges tended to
      make decisions consistent with the majority opinion. But when judges disagreed
      with the majority opinion, they more often did so to find a defendant incompetent
      than competent, suggesting a generally conservative approach. Overall, results
      reveal moderate agreement among independent evaluators in routine practice. But
      we discuss the potential for standardized training and methodology to further
      improve the field reliability of CST evaluations.

PMID- 22471418
TI  - A perpetrator's accent impairs witnesses' memory for physical appearance.
AB  - Sometimes witnesses to crimes must remember both a perpetrator's appearance and
      voice. Drawing upon multiple resource theory as well as previous findings that
      processing foreign-accented speech is more demanding than processing unaccented
      speech, we hypothesized that a perpetrator's accent can impair memory for his or
      her appearance. In Experiment 1, we used a secondary visual search task to
      demonstrate that processing an accented versus unaccented message demands more
      cognitive resources. In two additional experiments, we extended that result by
      showing that witnesses trying to encode information spoken by a perpetrator with
      an accent rather than no accent provided poorer physical descriptions of him and
      identified his voice less accurately. We also found that witnesses who heard a
      more versus less detailed message reported fewer correct details about the
      perpetrator's appearance (Experiment 2), and a more rather than less threatening
      message led to less accurate descriptions (Experiment 3).

PMID- 22471419
TI  - Harmless error analysis: How do judges respond to confession errors?
AB  - In Arizona v. Fulminante (1991), the U.S. Supreme Court opened the door for
      appellate judges to conduct a harmless error analysis of erroneously admitted,
      coerced confessions. In this study, 132 judges from three states read a murder
      case summary, evaluated the defendant's guilt, assessed the voluntariness of his
      confession, and responded to implicit and explicit measures of harmless error.
      Results indicated that judges found a high-pressure confession to be coerced and
      hence improperly admitted into evidence. As in studies with mock jurors, however,
      the improper confession significantly increased their conviction rate in the
      absence of other evidence. On the harmless error measures, judges successfully
      overruled the confession when required to do so, indicating that they are capable
      of this analysis.

PMID- 22471420
TI  - Femtogram doubly clamped nanomechanical resonators embedded in a high-Q two
      dimensional photonic crystal nanocavity.
AB  - We demonstrate a new optomechanical device system which allows highly efficient
      transduction of femtogram nanobeam resonators. Doubly clamped nanomechanical
      resonators with mass as small as 25 fg are embedded in a high-finesse two
      dimensional photonic crystal nanocavity. Optical transduction of the fundamental
      flexural mode around 1 GHz was performed at room temperature and ambient
      conditions, with an observed displacement sensitivity of 0.94 fm/Hz(1/2).
      Comparison of measurements from symmetric and asymmetric double-beam devices
      reveals hybridization of the mechanical modes where the structural symmetry is
      shown to be the key to obtain a high mechanical quality factor. Our novel
      configuration opens the way for a new category of "NEMS-in-cavity" devices based
      on optomechanical interaction at the nanoscale.

PMID- 22471421
TI  - Follicular dynamics, interval to ovulation and fertility after AI in short-term
      progesterone and PGF2alpha oestrous synchronization protocol in sheep.
AB  - The study was aimed to assess the influence that short-term progesterone
      treatments have on follicular dynamics, oestrus and ovulation in sheep. The
      treatment was tested thereafter in a field trial to assess its fertility after AI
      with fresh semen. In a first experiment, 12 ewes without CL were grouped to
      receive a new (n = 6) or used CIDR (n = 6) for 7 days and blood samples were
      obtained to follow plasma progesterone profiles. In a second experiment, 39
      cycling ewes were synchronized by a 7-day P4+PGF2alpha protocol using a new (n =
      20) or a 7-day used CIDR (n = 19). Half of both groups received 400 IU eCG and
      half remained untreated as controls. Ultrasound ovarian examination and oestrous
      detection were used to compare follicular dynamics, oestrus and ovulation in both
      groups. In a third experiment, 288 ewes in 3 farms were synchronized by the short
      term P4+PGF2alpha+eCG protocol and ewes were AI with fresh semen 24 h after
      oestrous detection. Lambing performance was used to test the fertility of the
      treatment. In Experiment 1, ewes with new inserts presented higher P4
      concentration than ewes with used inserts throughout the sampling period (p <
      0.05) and exhibited a P4 peak at days 1-2 of the treatment that was not observed
      in ewes with used inserts. In Experiment 2, ewes treated with new and used
      inserts show similar ovarian and behavioral traits (p > 0.10). However, ewes
      treated with eCG show shorter interval to oestrus (p = 0.004) and tend to have
      larger mature CL (p = 0.06). In Experiment 3, oestrous presentation and lambing
      performance after AI with fresh semen was considered normal compared to published
      results. Results suggest that the oestrous synchronization protocol based on
      P4+PGF2alpha allows little control of follicular dynamics without compromising
      fertility after AI with fresh semen provided that eCG is added at the end of the
      treatment.

PMID- 22471422
TI  - Acupuncture with manual and low frequency electrical stimulation as experienced
      by women with polycystic ovary syndrome: a qualitative study.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) affects 5-10 percent of all fertile
      women and is associated with anovulation/oligoovulation, hyperandrogenism, and
      polycystic ovaries. Pharmacological treatment is often effective but associated
      with unwanted side effects. Acupuncture treatments have been shown to improve
      menstrual bleeding patterns and ovulation as well as hyperandrogenism, without
      side effects. The purpose of the present study was to describe the experience of
      acupuncture for women diagnosed with PCOS. METHODS: Eight women with PCOS living
      in western Sweden, were interviewed following repeated acupuncture treatments.
      Data was analyzed using systematic text condensation as described by Malterud.
      RESULTS: The experience of acupuncture for women diagnosed with PCOS can be
      described in five categories; the experience of hope, getting results, feelings
      of responsibility, skepticism and proof of effect, and feeling normal.
      CONCLUSION: Since acupuncture is a promising treatment for the symptoms of the
      common syndrome PCOS, the present study adds to the knowledge base by providing
      the important experiences of patients receiving the treatment. Acupuncture
      provides a possibility for patients to gain hope as the treatment shows results.
      The results show that acupuncture empowers the patients to take responsibility
      for their future well-being, although they may have been initially skeptical to
      the treatment. Because the syndrome had affected them for some time, even small
      changes offered a chance for them to feel that their bodies were capable of
      normal function.

PMID- 22471423
TI  - Rapid transgene expression in multiple precursor cell types of adult rat
      subventricular zone mediated by adeno-associated type 1 vectors.
AB  - The adult rat brain subventricular zone (SVZ) contains proliferative precursors
      that migrate to the olfactory bulb (OB) and differentiate into mature neurons.
      Recruitment of precursors constitutes a potential avenue for brain repair. We
      have investigated the kinetics and cellular specificity of transgene expression
      mediated by AAV2/1 vectors (i.e., adeno-associated virus type 2 pseudotyped with
      AAV1 capsid) in the SVZ. Self-complementary (sc) and single-stranded (ss) AAV2/1
      vectors mediated efficient GFP expression, respectively, at 17 and 24 hr
      postinjection. Transgene expression was efficient in all the rapidly
      proliferating cells types, that is, Mash1(+) precursors (30% of the GFP(+)
      cells), Dlx2(+) neuronal progenitors (55%), Olig2(+) oligodendrocyte progenitors
      (35%), and doublecortin-positive (Dcx(+)) migrating cells (40%), but not in the
      slowly proliferating glial fibrillary acidic protein-positive (GFAP(+)) neural
      stem cell pool (5%). Because cell cycle arrest by wild-type and recombinant AAV
      has been described in primary cultures, we examined SVZ proliferative activity
      after vector injection. Indeed, cell proliferation was reduced immediately after
      vector injection but was normal after 1 month. In contrast, migration and
      differentiation of GFP(+) precursors were unaltered. Indeed, the proportion of
      Dcx(+) cells was similar in the injected and contralateral hemispheres.
      Furthermore, 1 month after vector injection into the SVZ, GFP(+) cells, found, as
      expected, in the OB granular cell layer, were mature GABAergic neurons. In
      conclusion, the rapid and efficient transgene expression in SVZ neural precursors
      mediated by scAAV2/1 vectors underlines their potential usefulness for brain
      repair via recruitment of immature cells. The observed transient precursor
      proliferation inhibition, not affecting their migration and differentiation, will
      likely not compromise this strategy.

PMID- 22471424
TI  - Individual-based primary prevention of cardiovascular disease in Cambodia and
      Mongolia: early identification and management of hypertension and diabetes
      mellitus.
AB  - BACKGROUND: To assess the coverage of individual-based primary prevention
      strategies for cardiovascular disease (CVD) in Cambodia and Mongolia:
      specifically the early identification of hypertension and diabetes mellitus,
      major proximate physiological CVD risk factors, and management with
      pharmaceutical and lifestyle advice interventions. METHODS: Analysis of data
      collected in national cross-sectional STEPS surveys in 2009 (Mongolia) and 2010
      (Cambodia) involving participants aged 25-64 years: 5433 in Cambodia and 4539 in
      Mongolia. RESULTS: Mongolia has higher prevalence of CVD risk factors than
      Cambodia--hypertension (36.5% versus 12.3%), diabetes (6.3% versus 3.1%),
      hypercholesterolemia (8.5% versus 3.2%), and overweight (52.5% versus 15.5%). The
      difference in tobacco smoking was less notable (32.1% versus 29.4%).Coverage with
      prior testing for blood glucose in the priority age group 35-64 years remains
      limited (16.5% in Cambodia and 21.7% in Mongolia). Coverage is higher for
      hypertension. A large burden of both hypertension and diabetes remains
      unidentified at current strategies for early identification: only 45.4%
      (Cambodia) to 65.8% (Mongolia) of all hypertensives and 22.8% (Mongolia) to 50.3%
      (Cambodia) of all diabetics in the age group 35-64 years had been previously
      diagnosed. Approximately half of all hypertensives and of all diabetics in both
      countries were untreated. 7.2% and 12.2% of total hypertensive population and
      5.9% and 16.1% of total diabetic population in Cambodia and Mongolia,
      respectively, were untreated despite being previously diagnosed.Only 24.1% and
      28.6% of all hypertensives and 15.9% and 23.9% of all diabetics in Mongolia and
      Cambodia, respectively were adequately controlled. Estimates suggest deficits in
      delivery of important advice for lifestyle interventions. CONCLUSIONS:
      Multifaceted strategies are required to improve early identification, initiation
      of treatment and improving quality of treatment for common CVD risk factors.
      Periodic population-based surveys including questions on medical and treatment
      history and the context of testing and treatment can facilitate monitoring of
      individual-based prevention strategies.

PMID- 22471425
TI  - Identification of foreign bodies on the ocular surface after uneventful
      intravitreal injections.

PMID- 22471426
TI  - The percutaneous suspension suture.

PMID- 22471427
TI  - Inpatient safety trends in laparoscopic and open nephrectomy for renal tumours.
AB  - Study Type--Cohort study Level of Evidence 2b. What's known on the subject? and
      What does the study add? Laparoscopic radical nephrectomy for renal cancer
      provides equivalent long-term cancer control with shorter hospital stays, less
      postoperative pain, and faster resumption of normal activities, but it has
      diffused slowly into clinical practice, perhaps as a result of perceptions about
      safety. Patient safety outcomes for laparoscopic and open radical nephrectomy
      using validated measures remain incompletely characterized. This is the first
      study to investigate peri-operative outcomes of radical nephrectomy using
      validated patient safety measures. We found a 32% decreased probability of
      adverse patient safety events occurring in laparoscopic compared with open
      radical nephrectomy. The safety benefits of laparoscopy were attained only after
      10% of cases were completed laparoscopically--a proportion some have proposed as
      the 'tipping point' for the adoption of surgical innovations. This observation
      could have implications for patient safety in the setting of diffusion of new
      surgical techniques. OBJECTIVE: * To compare peri-operative adverse patient
      safety events occurring in laparoscopic radical nephrectomy (LRN) with those
      occurring in open radical nephrectomy (ORN). METHODS: * We used the US Nationwide
      Inpatient Sample to identify patients undergoing kidney surgery for renal tumours
      from 1998 to 2008. * We used patient safety indicators (PSIs), which are
      validated measures of preventable adverse outcomes, and multivariate regression
      to analyse associations of surgery type with patient safety. RESULTS: * Open
      radical nephrectomy accounted for 235,098 (89%) cases while 28,609 (11%) cases
      were LRN. * Compared with ORN, LRN patients were more likely to be male (P=
      0.048), have lower Charlson comorbidity scores (P < 0.001), and to undergo
      surgery at urban (P < 0.001) and teaching (P < 0.001) hospitals. * PSIs occurred
      in 18,714 (8%) of ORN and 1434 (5%) of LRN cases (P < 0.001). * On multivariate
      analysis, LRN was associated with a 32% decreased probability of any PSI
      (adjusted odds ratio 0.68, 95% confidence interval: 0.6 to 0.77, P < 0.001).
      Stratification by year showed that this difference was initially manifested in
      2003, when the proportion of LRN cases first exceeded 10%. CONCLUSIONS: *  We
      found that LRN was associated with substantially superior peri-operative patient
      safety outcomes compared with ORN, but only after the national prevalence of LRN
      exceeded 10%. * Further study is needed to explain these patterns and promote the
      safe diffusion of novel surgical therapies into broad practice.

PMID- 22471428
TI  - Isopentenyl diphosphate isomerase catalyzed reactions in D2O: product release
      limits the rate of this sluggish enzyme-catalyzed reaction.
AB  - The E. coli isopentenyl diphosphate isomerase (IDI) catalyzed reaction of
      isopentenyl diphosphate (IPP) in D(2)O gives a 66% yield of dimethylallyl
      diphosphate labeled with deuterium at the (E)-methyl group (d-DMAPP) and a 34%
      yield of IPP labeled with 1 mol of deuterium at C-2 (d-IPP). This shows that the
      release to D(2)O of the initial product of the IDI-catalyzed reaction (d-DMAPP)
      is slower than its conversion to d-IPP. Product dissociation is therefore rate
      determining for isomerization of IPP with a rate constant k(dis) ~ k(cat) = 0.08
      s(-1). The data provide an estimated rate constant of k(as) = 6 * 10(3) M(-1) s(
      1) for binding of DMAPP to E. coli IDI that is similar to rate constants
      determined for the binding of N-protonated 2-amino ethyl diphosphate intermediate
      analogs to IDI from yeast [Reardon, J. E.; Abeles, R. H. Biochemistry1986, 25,
      5609-5616]. We propose that ligand binding to IDI is relatively slow because
      there is a significant kinetic barrier to reorganization of the initial encounter
      complex between enzyme, substrate, and an essential Mg(2+) to form the Michaelis
      complex where the metal cation bridges the protein and the substrate diphosphate
      group.

PMID- 22471429
TI  - Interaction of fibrin with red blood cells: the role of iron.
AB  - Activation of coagulation pathways results in the formation of hemostatic fibrin
      plugs. Under normal physiologic conditions fibrin clots are gradually, albeit
      completely, degraded by a fibrinolytic enzyme system to ensure proper wound
      healing and/or blood vessel patency. Yet in pathological situations, thrombi are
      not effectively removed, leading to chronic thrombosis. The susceptibility of
      blood clots to enzymatic degradation depends on the structure and properties of
      fibrin fibers. Many factors have been suspected as culprits, including red blood
      cells (RBCs) that become transiently trapped within fibrin mesh. Here, the
      authors show that there is indeed a specific interaction between RBCs and fibrin
      like fibers identified here as dense matted deposits (DMDs) by means of scanning
      electron microscopy (SEM). It is emphasized that such interactions can be
      observed in ischemic stroke patients, but not from healthy subjects. However,
      DMD/RBC aggregates can be induced in normal blood by the additions of trivalent
      iron ions. The plausible mechanism of the enhanced fibrin-red blood cell
      interaction is based on the previously described iron-induced generation of
      hydroxyl radicals. These radicals cause, in turn, non-enzymatic formation of
      fibrinogen aggregates remarkably resistant to fibrinolysis that are also similar
      to DMDs described in this paper. In conclusion, this relatively simple SEM
      analysis may become a convenient tool for diagnosing prothrombotic conditions
      associated with iron overload. It is suggested that future research on prevention
      and treatment of ischemic stroke and other thrombosis associated diseases should
      include testing of iron-chelating and hydroxyl radical-scavenging agents.

PMID- 22471430
TI  - A clone of elusive parents: gonadotroph adenoma-female type.
AB  - A 69-year-old woman presented with visual disturbance. Perimetry testing revealed
      a bitemporal hemianopia. Brain MRI demonstrated a 2.2-cm gadolinium-enhancing
      pituitary mass. Previously she had been treated for hypothyroidism, hypertension,
      and dyslipidemia. She had hyperprolactinemia. Endoscopic transsphenoidal
      debulking improved her visual field defects. Histology showed a chromophobic
      adenoma. Electron microscopy showed elongated, polar cells with long, slender
      processes. The small uniform secretory granules were peripherally disposed,
      collecting heavily within cell processes. Based on electron microscopical
      characteristics the tumor is consistent with an ACTH-negative female gonadotroph
      adenoma. The parent cell of this rare variant of a pituitary adenoma is yet
      unknown.

PMID- 22471431
TI  - Iron-induced damage in corpus striatal cells of neonatal rats: attenuation by
      folic acid.
AB  - BACKGROUND: Iron supplementation is recommended during pregnancy to meet the
      needs of the rapidly growing fetus. However, its intake is associated with the
      generation of destructive free radicals, i.e., oxidative damage to the fetal
      brain. Folic acid supplementation is needed during pregnancy to reduce the risk
      of neural tube defects. HYPOTHESIS: Intake of folic acid can ameliorate the
      morphological features of cell damage in the striatal tissue (brain of neonatal
      rats) associated with the intake of iron. OBJECTIVES AND METHODS: To test this
      hypothesis, an animal model (pregnant Albino rats) was established. The animals
      were divided into three groups: group A, control animals treated with saline
      only; group B, animals treated with iron gluconate; and group C, animals treated
      concomitantly with iron gluconate and folic acid. The striatal brain tissues of
      the neonates were examined for features of cellular damage, using
      immunohistological and ultrastructural methods. RESULTS: The authors found
      significant variations among the three groups. The intake of iron (group B) and
      its deposition in the striatal tissue (neurons and glial cells) was associated
      with changes indicative of both cellular injury and regeneration. The former
      includes neuronal apoptosis and necrosis, and destruction of the organelles,
      including the mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes
      of the neurons and glial cells. The latter includes microgliosis, astrogliosis,
      upregulation of glial fibrillary acidic protein, and inducible nitric oxide
      synthase. These changes were absent in the striatal tissue of the control group
      (group A) and in animals treated concomitantly with both iron gluconate and folic
      acid (group C). CONCLUSION: Intake of folic acid can protect the neonatal
      striatal tissue against iron-induced oxidative stress damage.

PMID- 22471432
TI  - Trabecular meshwork in normal and pathological eyes.
AB  - PURPOSE: The impact of glycosaminoglycans on intraocular pressure in glaucoma
      patients and in healthy young or aging subjects is explored. MATERIALS AND
      METHODS: Thirty small autoptic samples were harvested from the tissue localized
      around the iridocorneal angle of the eye, taking care not to cause aesthetic
      damage. The samples came from three groups (young, old, and subjects with
      glaucoma). All samples were divided in two fragments and both were used for
      morphological and biochemical analyses. Quantitative data were obtained from
      image analysis to correlate with biochemical values. All results were
      statistically analyzed. RESULTS: The findings show the following changes of
      iridocorneal angle are caused by glycosaminoglycans both in aging and in
      glacoumatous patients: (1) deposition of fibrous granular material and increased
      electron density of the structures close to the iridocorneal angle; and (2)
      strong decrease of hyaluronic acid content and increase of sulfated
      glycosaminoglycans. CONCLUSIONS: Similar to what happens in other tissues in the
      body, glycosaminoglycans of the human iridocorneal angle undergo physiological
      and pathological changes. The trabecular meshwork is the structure responsible
      for the regulation of the aqueous humor outflow that is often altered in primary
      open-angle glaucoma patients.

PMID- 22471433
TI  - Gelatinases A and B expression in human colorectal cancer in upper Egypt: a
      clinicopathological study.
AB  - AIM: Prognosis of colorectal carcinoma depends on many factors, such as age and
      sex of patient; location; multiplicity; local extent and size of tumor, bowel
      obstruction, or perforation; as well as tumor microscopic type and grade;
      vascular and perineural invasion; and nodal and distant metastasis. The matrix
      metalloproteinases (MMPs) are a family of proteolytic enzymes strongly implicated
      in tumor invasion and metastasis, hence in tumor prognosis. The purpose of this
      study was to assess the role of MMP-2 and MMP-9 expression in colorectal
      tumorigenesis, invasion, and metastasis, hence their prognostic values. METHOD:
      Immunohistochemical analysis of MMP-2 and MMP-9 in colorectal cancer cells, an
      immunohistochemical score based on the intensity of immunoreactivity and
      proportion of immunoreactive cells that established for each MMP, and correlation
      of this expression with the established prognostic factors. RESULTS: MMP-2 was
      expressed in 81.8% (strong expression in 40%) of cases, and MMP-9 was expressed
      in 72% (strong expression in 35%) of cases. CONCLUSIONS: MMP-2 and MMP-9 are
      widely expressed in colorectal carcinoma, suggesting significant diagnostic and
      prognostic values in these tumors. Increased levels of MMP-2 and MMP-9 protein
      expression in colorectal carcinoma tissues as compared to normal tissues suggest
      their association with colorectal tumor invasion and metastasis and that they
      could be targets for intervention and therapy in colorectal carcinoma.

PMID- 22471434
TI  - The emerging issue of human resident arterial progenitors: the contribution of
      organ culture.
AB  - Human femoral arteries were cultured up to 56 days. Samples were processed for
      light, immunohistochemical, and transmission electron microscopy. Arteries became
      rapidly depopulated; at day 42, an endothelial lining (CD31(+), Weibel-Palade
      bodies) developed on the intima; endothelium was in continuity with mesenchymal
      stromal cells (CD44(+), CD90(low), CD105(low)) placed on adventitia. The media
      adventitia area showed heterogeneous cell populations. In long-term organ
      culture, femoral artery develops a continuous cell coverage that differentiates
      to endothelium on the intima exclusively. This suggests that distinct
      topographical factors, such as resident progenitors and/or matrix signals, are
      able to regulate vascular homeostasis in adult life.

PMID- 22471435
TI  - Pancreatic PEComa: a case report with ultrastructural localization of HMB-45
      within melanosomes.
AB  - PEComas (perivascular epithelioid cell tumors) represent a group of mesenchymal
      neoplasms showing characteristic morphologic, immunohistochemical,
      ultrastructural, and genetic features. These neoplasms are usually considered
      benign, being often well circumscribed by a thin capsule and showing scarce
      atypia. However, in some cases, they show local invasion and multiple metastases
      and cause the patient's death. PEComas have been found in many locations, but
      only 7 cases have been described in the pancreas to date. Here, the authors
      report an additional case of this rare neoplasm and demonstrate the HMB-45
      immunoreactivity of melanosomes or premelanosomes at the ultrastructural level.

PMID- 22471436
TI  - Cardiac neuroendocrine tumor with absence of sustentacular cells:
      immunohistochemical and ultrastructural findings.
AB  - A 68-year-old male presented with increased shortness of breath and intermittent
      chest pain. Cardiac catheterization along with echocardiogram imaging
      demonstrated 3-vessel coronary artery disease with severe left ventricular
      dysfunction and critical aortic stenosis. During coronary artery bypass surgery,
      a tumor was identified at the sulcus between the aorta and the right atrial
      appendage. This highly vascular tumor extended over the right coronary artery,
      prompting biopsy and further resection. Light microscopic evaluation showed
      packets of uniform round neoplastic cells without evidence of necrosis or
      increased mitotic figures. Immunohistochemical studies were positive for
      synaptophysin and weakly positive for chromogranin. Pankeratin, S-100, and GFAP
      stains were all negative. Ultrastructural examination of the neoplasm
      demonstrated numerous electron-dense secretory granules within the cytoplasm of
      the tumor cells. These secretory granules varied in size from 60 to 210  nm, with
      halos encircling many of them, suggesting the likelihood of epinephrine or
      norepinephrine granules. Within the specimen, abundant vascular spaces were
      identified, but no sustentactular cells were present. The patient agreed to
      undergo genetic testing, and a mutation in the succinate dehydrogenase complex
      subunit B (SDHB) was identified. This confirmed the molecular diagnosis of
      hereditary paraganglioma/pheochromocytoma syndrome. Now two years out from
      surgery, this patient continues to be asymptomatic in spite of the fact that his
      tumor was only partially resected.

PMID- 22471437
TI  - Light-chain deposition disease of the kidney: a case report.
AB  - A 41-year-old man was admitted for evaluation of nephrotic syndrome associated
      with microhematuria, hypertension, and moderate renal failure. In serum and urine
      samples, monoclonal IgG-lambda was detected. Bone marrow examination showed
      normal representation of all cell lines with normal range of plasma cells. Renal
      biopsy demonstrated diabetes-like nodular glomerulosclerosis. Immunofluorescence
      failed to demonstrate the presence of kappa or lambda light chains in the kidney.
      Electron microcopy showed granular electron-dense deposits along the glomerular
      basement membranes and in the mesangial nodules. The patient was diagnosed as
      having light-chain deposition disease (LCDD) without evidence of plasma cell
      dyscrasia. This report was designed to stress the significant challenges that
      remain in the diagnosis of LCDD-related glomerulopathy. The salient morphological
      features that help in making an accurate diagnosis are discussed.

PMID- 22471439
TI  - Plant stoichiometry at different scales: element concentration patterns reflect
      environment more than genotype.
AB  - All plant species require at least 16 elements for their growth and survival but
      the relative requirements and the variability at different organizational scales
      is not well understood. We use a fertiliser experiment with six willow (Salix
      spp.) genotypes to evaluate a methodology based on Euclidian distances for
      stoichiometric analysis of the variability in leaf nutrient relations of twelve
      of those (C, N, P, K, Ca, Mg, Mn, S, Fe, Zn, B, Cu) plus Na and Al. Differences
      in availability of the elements in the environment was the major driver of
      variation. Variability between leaves within a plant or between individuals of
      the same genotype growing in close proximity was as large as variability between
      genotypes. Elements could be grouped by influence on growth: N, P, S and Mn
      concentrations follow each other and increase with growth rate; K, Ca and Mg
      uptake follow the increase in biomass; but uptake of Fe, B, Zn and Al seems to be
      limited. The position of Cu lies between the first two groups. Only for Na is
      there a difference in element concentrations between genotypes. The three groups
      of elements can be associated with different biochemical functions.

PMID- 22471438
TI  - Running-induced anxiety is dependent on increases in hippocampal neurogenesis.
AB  - Exercise, specifically voluntary wheel running, is a potent stimulator of
      hippocampal neurogenesis in adult mice. In addition, exercise induces behavioral
      changes in numerous measures of anxiety in rodents. However, the physiological
      underpinnings of these changes are poorly understood. To investigate the role of
      neurogenesis in exercise-mediated anxiety, we examined the cellular and
      behavioral effects of voluntary wheel running in mice with a reduction in
      hippocampal neurogenesis, achieved through conditional deletion of ataxia
      telangiectasia-mutated and rad-3-related protein (ATR), a cell cycle checkpoint
      kinase necessary for normal levels of neurogenesis. Following hippocampal
      microinjection of an adeno-associated virus expressing Cre recombinase to delete
      ATR, mice were exposed to 4 weeks of voluntary wheel running and subsequently
      evaluated for anxiety-like behavior. Wheel running resulted in increased cell
      proliferation and neurogenesis, as measured by bromodeoxyuridine and
      doublecortin, respectively. Wheel running also resulted in heightened anxiety in
      the novelty-induced hypophagia, open field and light-dark box tests. However,
      both the neurogenic and anxiogenic effects of wheel running were attenuated
      following hippocampal ATR deletion, suggesting that increased neurogenesis is an
      important mediator of exercise-induced anxiety.

PMID- 22471440
TI  - The controllability beliefs scale used with carers of people with intellectual
      disabilities: psychometric properties.
AB  - BACKGROUND: Beliefs about the controllability of behaviour have been consistently
      shown to be important in understanding the responses of carers to the challenging
      behaviour of people with intellectual disabilities (IDs). This paper reports the
      reliability and validity of the controllability beliefs scale (CBS), a 15-item
      measure of beliefs regarding the controllability of challenging behaviour when
      used with carers of people with IDs. METHODS: Two hundred and sixty-four carers
      of people with IDs completed the CBS, 74 people also completed the modified
      attributional style questionnaire and the self-injury behavioural understanding
      questionnaire scale to determine concurrent and convergent validity and 34 people
      completed the scale twice within a 2- to 4-week period to determine test-retest
      reliability. RESULTS: The scale has a two-factor structure and has adequate
      internal reliable. The scale is significantly correlated with the
      controllability, internality and stability items from the Modified Attributional
      Style Questionnaire, showed expected associations with behavioural and internal
      emotional understanding items from the self-injury behavioural understanding
      questionnaire. The scale has good test-retest reliability. CONCLUSIONS: The data
      support use of the CBS in clinical practice and research to assess carers'
      beliefs regarding challenging behaviour of people with IDs.

PMID- 22471441
TI  - PhosphoSiteAnalyzer: a bioinformatic platform for deciphering phospho proteomes
      using kinase predictions retrieved from NetworKIN.
AB  - Phosphoproteomic experiments are routinely conducted in laboratories worldwide,
      and because of the fast development of mass spectrometric techniques and
      efficient phosphopeptide enrichment methods, researchers frequently end up having
      lists with tens of thousands of phosphorylation sites for further interrogation.
      To answer biologically relevant questions from these complex data sets, it
      becomes essential to apply computational, statistical, and predictive analytical
      methods. Here we provide an advanced bioinformatic platform termed
      "PhosphoSiteAnalyzer" to explore large phosphoproteomic data sets that have been
      subjected to kinase prediction using the previously published NetworKIN
      algorithm. NetworKIN applies sophisticated linear motif analysis and contextual
      network modeling to obtain kinase-substrate associations with high accuracy and
      sensitivity. PhosphoSiteAnalyzer provides an algorithm to retrieve kinase
      predictions from the public NetworKIN webpage in a semiautomated way and applies
      hereafter advanced statistics to facilitate a user-tailored in-depth analysis of
      the phosphoproteomic data sets. The interface of the software provides a high
      degree of analytical flexibility and is designed to be intuitive for most users.
      PhosphoSiteAnalyzer is a freeware program available at
      http://phosphosite.sourceforge.net . 

PMID- 22471442
TI  - Computational toxicological investigation on the mechanism and pathways of
      xenobiotics metabolized by cytochrome P450: a case of BDE-47.
AB  - Understanding the transformation mechanism and products of xenobiotics catalyzed
      by cytochrome P450 enzymes (CYPs) is vital to risk assessment. By density
      functional theory computation with the B3LYP functional, we simulated the
      reaction of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) catalyzed by the active
      species of CYPs (Compound I). The enzymatic and aqueous environments were
      simulated by the polarizable continuum model. The results reveal that the
      addition of Compound I to BDE-47 is the rate-determining step. The addition of
      Compound I to the ipso and nonsubstituted C atoms forms tetrahedral sigma-adducts
      that further transform into epoxides. Hydroxylation of the epoxides leads to
      hydroxylated polybrominated diphenyl ethers and 2,4-dibromophenol. The addition
      to the Br-substituted C2 and C4 atoms has a higher barrier than addition to the
      nonsubstituted C atoms, forming phenoxide and cyclohexadienone which subsequently
      undergo debromination/hydroxylation. A novel mechanism was identified in which
      the approach of Compound I to C2 led to formation of a phenoxide and an expelled
      Br(-) ion. The predicted products were consistent with the metabolites identified
      by others. As a first attempt to simulate the enzymatic transformation of a
      polycyclic compound, this study may enlighten a computational method to predict
      the biotransformation of xenobiotics catalyzed by CYPs.

PMID- 22471443
TI  - Mechanistic studies on the application of DNA aptamers as inhibitors of 2
      oxoglutarate-dependent oxygenases.
AB  - The Escherichia coli (E. coli) AlkB protein and its functional human homologues
      belong to a subfamily of 2-oxoglutarate (2OG) dependent oxygenases (2OG
      oxygenases for simplicity) that enable the repair of cytotoxic methylation damage
      in nucleic acids and that catalyze t-RNA oxidations. DNA alkylation is a major
      mechanism of action for cytotoxic anticancer drugs. Thus, the inhibition of
      oxidative demethylation, catalyzed by these enzymes, has the potential to improve
      the efficacy of chemotherapies. Here we report that oligonucleotide aptamers
      constitute a new class of potent inhibitors of 2OG oxygenases. DNA aptamers can
      selectively bind to AlkB, with nanomolar affinity, and efficiently inhibit
      catalysis. The mechanism of inhibition was studied by capillary electrophoresis
      (CE) with laser-induced fluorescence (LIF) detection. Inhibition constants of the
      aptamers were determined and shown to correlate well with K(d) values. The
      results of kinetic analyses imply that the aptamers bind AlkB away from the
      active site. Our findings should stimulate the development of oligonucleotide
      aptamers for human homologues of AlkB and further their study as potential
      enhancers of chemotherapy efficiency.

PMID- 22471444
TI  - Expression of survivin, Bcl-2 and Bax proteins in the domestic cat (Felis catus)
      endometrium during the oestrus cycle.
AB  - Apoptosis has been shown to be an important regulator of endometrium function. To
      clarify the regulation of apoptosis in the cat endometrium during the normal
      oestrus cycle, the expressions of the apoptosis-related proteins (Bcl-2 and Bax)
      and their correlation to the inhibitor of apoptosis protein Survivin were
      analysed using immunohistochemistry. The TUNEL technique (TdT-mediated dUTP nick
      end labelling) was also used to detect DNA fragmentation characteristic of
      apoptotic cells. The results demonstrated that TUNEL labelling is not effective
      for the detection of apoptosis in cat endometrium. Survivin was expressed in the
      luminal and glandular epithelial cells of cat endometrium during all phases of
      the oestrus cycle. Survivin was localized in both the cytoplasm and nuclei of
      superficial and deep uterine gland cells during the luteal phase, while only
      cytoplasmic staining was observed during the follicular and anoestrus phases. Bax
      immunoreactivity in the cytoplasm of luminal and glandular epithelial cells as
      well as the smooth muscle cells of blood vessels was weak in the anoestrus phase.
      Compared with anoestrus, the intensity of Bax immunostaining was moderate in the
      follicular phase and increased dramatically in the luteal phase. Bcl-2
      immunostaining in the cytoplasm of luminal and glandular epithelial cells was
      moderate in the anoestrus phase. During the early follicular phase, cytoplasmic
      Bcl-2 immunostaining was detected mostly in glandular epithelial cells. In the
      mid-follicular phase, in glands, the amount of Bcl-2 protein increased
      progressively from the superficial to the deep layer. In contrast, the expression
      of Bcl-2 decreased in the secretory phase, being very low or absent in the mid-
      and late luteal phases. The overall results suggest that Survivin, Bax and Bcl-2
      proteins may cooperatively contribute to cell apoptosis and cell proliferation in
      the cat uterus during the oestrus cycle.

PMID- 22471446
TI  - Re: Assessment of macular pigment optical density (MPOD) in patients with
      unilateral wet age-related macular degeneration (AMD).

PMID- 22471447
TI  - Non-steroidal anti-inflammatory drugs and cancer, with an especial focus on
      esophageal cancer.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have been extensively used for
      relief of pain and fever, and prevention of cardiovascular and cerebrovascular
      diseases for several decades. Recently, the use of these compounds has been
      reported to be associated with reduction in occurrence of a variety of cancers.
      In this paper, we reviewed anti-cancer mechanisms of NSAIDs and their potential
      preventive and even therapeutic effects on cancer, focusing on esophageal cancer
      in particular.

PMID- 22471445
TI  - Complexity of the microglial activation pathways that drive innate host responses
      during lethal alphavirus encephalitis in mice.
AB  - Microglia express multiple TLRs (Toll-like receptors) and provide important host
      defence against viruses that invade the CNS (central nervous system). Although
      prior studies show these cells become activated during experimental alphavirus
      encephalitis in mice to generate cytokines and chemokines that influence virus
      replication, tissue inflammation and neuronal survival, the specific PRRs
      (pattern recognition receptors) and signalling intermediates controlling
      microglial activation in this setting remain unknown. To investigate these
      questions directly in vivo, mice ablated of specific TLR signalling molecules
      were challenged with NSV (neuroadapted Sindbis virus) and CNS viral titres,
      inflammatory responses and clinical outcomes followed over time. To approach this
      problem specifically in microglia, the effects of NSV on primary cells derived
      from the brains of wild-type and mutant animals were characterized in vitro. From
      the standpoint of the virus, microglial activation required viral uncoating and
      an intact viral genome; inactivated virus particles did not elicit measurable
      microglial responses. At the level of the target cell, NSV triggered multiple
      PRRs in microglia to produce a broad range of inflammatory mediators via non
      overlapping signalling pathways. In vivo, disease survival was surprisingly
      independent of TLR-driven responses, but still required production of type-I IFN
      (interferon) to control CNS virus replication. Interestingly, the ER (endoplasmic
      reticulum) protein UNC93b1 facilitated host survival independent of its known
      effects on endosomal TLR signalling. Taken together, these data show that
      alphaviruses activate microglia via multiple PRRs, highlighting the complexity of
      the signalling networks by which CNS host responses are elicited by these
      infections.

PMID- 22471448
TI  - Dietary turmeric potentially reduces the risk of cancer.
AB  - Turmeric, a plant rhizome that is often dried, ground and used as a cooking
      spice, has also been used medicinally for several thousand years. Curcumin, the
      phytochemical that gives turmeric its golden color, is responsible for most of
      the therapeutic effects of turmeric. In recent years curcumin has been studied
      for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer.
      Though many researchers are investigating turmeric/curcumin in cancer therapy,
      there is little epidemiologic information on the effects of turmeric consumption.
      With limited availability of pharmacologic interventions in many areas of the
      world, use of turmeric in the diet may help to alleviate some of the disease
      burden through prevention. Here we provide a brief overview of turmeric
      consumption in different parts of the world, cancer rates in those regions,
      possible biochemical mechanisms by which turmeric acts and practical
      recommendations based on the information available.

PMID- 22471449
TI  - Role of miRNAs in breast cancer.
AB  - miRNAs belong to an important class of endogenous molecules which are present in
      a wide range of organisms including animals, plants and viruses. They are
      involved in regulating expression of several genes inside a cell due to presence
      of complementary region against specific mRNA molecules. Altered expression
      patterns cause progression of multiple diseases inside an organism. They have
      also been confirmed to be involved in different cancers including breast cancer.
      In this review, we discuss role of miRNAs with respect to uncontrolled division
      of cells, promotion, progression and metastasis in breast cancer.

PMID- 22471450
TI  - Evaluation of the efficacy of modified De Gramont and modified FOLFOX4 regimens
      for adjuvant therapy of locally advanced rectal cancer.
AB  - OBJECTIVE: To evaluate the efficacy of modified De Gramont (mDG) and FOLFOX4
      (mFOLFOX4) regimens in patients with locally advanced rectal cancer (LARC).
      METHODS: Patients that received adjuvant chemotherapy (CT) for the treatment of
      LARC (stage II and III) were retrospectively evaluated. RESULTS: A total of 231
      patients were examined. Median age was 58 (range, 18-83) and, of these patients,
      36 (15.6%) had stage II and 195 (84.4%) had stage III disease. While the patients
      with stage II disease received only mDG regimen (36, 100.0%), of the patients
      with stage III disease, 71 (36.5%) received mDG and 124 (63.5%) received mFOLFOX4
      regimen. Patients with stage III disease showed recurrences more often, but this
      difference was not statistically significant. Similarly, for the patients with
      stage III disease, there was no statistically significant relation between the
      adjuvant CT regimen received and the rate of recurrence. In patients with stage
      II disease, who received mDG, median DFS was 101 months and median OS was 106
      months. For the patients with stage III disease, the patients that received mDG
      showed a median DFS of 78 months and a median OS of 96 months, while the patients
      that received mFOLFOX4 had a median DFS of 51 months and a median OS of 78
      months. Although, for the patients with stage III disease, there are major
      differences between the two different regimens of CT in terms of DFS and OS, this
      difference was not statistically significant.When the results were evaluated from
      the perspective of toxicity, the patients that received mFOLFOX4 showed more
      toxicity. Neurotoxicity, which was seen in the patients that were given mFOLFOX4,
      was the most prominent toxicity. CONCLUSIONS: mDG and mFOLFOX4 regimens are
      applicable regimens as adjuvant CT for the treatment of LARC.

PMID- 22471451
TI  - Lack of diagnostic potential of Dickkopf-1 in colon and rectum cancers.
AB  - The Wnt/b-catenin signalling pathway plays crucial roles in development and its
      aberrant activation is an initial and crucial event in the majority of colon
      cancers. The Dickkopf-1 (Dkk-1) gene encodes an extracellular Wnt inhibitor that
      blocks the formation of signalling receptor complexes at the plasma membrane.
      Here, we report the serum levels of Dkk1 in colorectal cancer patients without
      any therapy. The levels were determined by enzyme-linked immunosorbent assay
      (ELISA) in 135 colon and 160 rectum cancer patients, as well as 90 healthy
      subjects. Data analyses were performed using SPSS software (SPSS 16, Chicago,
      IL). There were no significant differences among the groups for Dkk-1 (p=0.363).
      In conclusion, the present study did not confirm that serum Dkk-1 levels could
      have any diagnostic potential in colon and rectum cancers.

PMID- 22471452
TI  - A community based smoking cessation intervention trial for rural Kerala, India.
AB  - OBJECTIVES: An attempt was made to compare tobacco prevalence and socioeconomic
      factors of two groups (intervention and control) from a selected rural community
      in Thiruvananthapuram, Kerala, India. METHODS: Data were collected from resident
      males in the age group of 18.0 to 60.0 years from 4 randomly allocated Community
      Development Blocks of rural Thiruvananthapuram district (2 intervention and
      control groups). Trained Accredited Social Health Activists workers were utilised
      to collect data from both the groups through a face to face interview. RESULTS:
      Among 3304 subjects were interviewed, the overall prevalence of smokers was 28%
      (n=928) (mean age=44.4 years, SD=9.2 years). Socio-economic status (SES) score
      points indicated that majority of smokers belonged to the upper lower SES
      category (61%) (mean SES score =10, SD= 3) and among non-smokers, the
      participants mainly belonged to the lower middle SES score (45%) (mean SES score
      =12, SD= 3) (p-value=0.0001). Among the 928 smokers, 474 subjects were in the
      intervention area (mean age =44.56 years, SD =9.66 years) and 454 in the control
      area (mean age= 44.47 years, SD =10.30 years). No significant difference was
      found between the intervention and control groups according to age (p=0.89) and
      SES (p=0.11). Majority of smokers in the intervention and control areas were from
      the upper lower SES group (64.14% and 57.17%). CONCLUSION: Smoking continues to
      be a predominant public health problem among males in rural Kerala particularly
      among lower socio-economic population. Apart from strengthening legislation,
      multiple cost effective intervention approaches are required to reduce tobacco
      consumption in the community.

PMID- 22471453
TI  - Retrospective analysis of results of treatment for nasopharyngeal carcinoma in
      Penang General Hospital from 2001-2005.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the commonest cancers
      encountered in Malaysia. This study aimed to evaluate the treatment outcomes for
      patients with NPC treated in Penang General Hospital with specific analysis of
      prognostic clinicopathological features and treatment modalities. MATERIALS AND
      METHODS: This retrospective study examined NPC patients between 1st January 2001
      and 31st December 2005 in Penang General Hospital. Survival analyses were
      performed using the Kaplan-Meier method and comparisons between groups were made
      using the log-rank test. Important prognostic factors including patient
      demographics, tumour and treatment factors were analysed using the Cox
      proportional hazard model. RESULTS: A total of 285 patients were identified with
      a median age of 51 years, 72.6% being males. The majority were Chinese (66%)
      followed by Malays (31.9%). Primary tumour stages (T stages) 3 and 4 were present
      in 18.6% and 34% of patients respectively, and nodal disease was present in
      80.4%. On overall AJCC staging, 29.1% had stage III and 50.2% had stage IV
      disease. Some 39.6% of patients had WHO type 3 histology and 7.4% had WHO type 1
      2 histology with the remainder having NPC with no subtype reported. Concurrent
      chemo-irradiation was the commonest treatment received by patients (51.9%)
      followed by radiotherapy alone (41.8%). The 5 year overall survival and cause
      specific survival were 33.3% and 42.7% respectively. Age group, T stage, N stage
      and WHO histological subtype were independent prognostic factors for overall
      survival on multivariate analysis. For cause specific survival they were T stage
      and N stage. CONCLUSION: The 5 years overall survival rate was 33.3%. This low
      figure is primarily due to late presentation. Efforts to detect NPC at earlier
      stages in Malaysia are urgently needed. These should include public education to
      increase awareness of the prevalence of this highly treatable disease.

PMID- 22471454
TI  - Effects of ABO and FUT2 genetic transcription absence on ABH histo-blood group
      antigen expression in lung cancer patients.
AB  - PURPOSE: To investigate the effect of alterations in mRNAs of ABO and FUT2 genes
      on the expression of ABH histo-blood group antigens in lung cancer patients.
      METHODS: Totals of 18 patients with blood group A, 14 with group B, 8 with group
      AB and 9 with group O, were assessed for blood group A/B/H antigens by
      immunohistochemical staining. Expression of A/B enzyme and FUT2 mRNA was detected
      in tumor tissues and corresponding lung tissues adjacent to tumors from lung
      cancer patients using RT-PCR. RESULTS: Expression of FUT2 and A/B enzyme mRNA in
      lung tissue adjacent to tumors was statistically greater than that in tumor
      tissues (chi2=14.118, P<0.001). Expression of FUT2 mRNA was statistically lower
      than that of A/B enzyme in tumor tissues from lung cancer patients whose blood
      group was A/B/AB (chi2=7.813, P=0.005). Only tumor tissues from 9 patients with
      mRNA expression of A/B enzyme and FUT2 gene lacked blood group antigens. In
      particular, expression of A/B antigens was not detected in five cases with A/B
      mRNA expression, a significant association being observed between the expression
      of enzyme and antigens (Pearson's R=0.867;kappa's coefficient =0.858, P<0.001).
      CONCLUSION: Expression of A/B/H blood group antigens was not detected in lung
      cancer tissues, which may have resulted from down-regulation of ABO/FUT2 gene
      transcription. Furthermore, the FUT2 gene may indirectly regulate expression of
      A/B blood group antigens by influencing H antigen expression.

PMID- 22471455
TI  - Functional SNPs in human C20orf54 gene influence susceptibility to esophageal
      squamous cell carcinoma.
AB  - OBJECTIVES: C20orf54, also known as a human riboflavin transporter 2 (RFT2),
      encodes an open reading frame protein RFT2 newly identified to play an important
      role in esophageal carcinogenesis by modulating riboflavin uptake. Missense cSNPs
      on exon 3,1172 C>A (T391M) and 1246A>G (I416V) have been suggested to modulate
      protein expression. The aim of present study was to explore the association of
      C20orf54 functional SNPs with susceptibility to esophageal squamous cell
      carcinoma (ESCC) in a northern Chinese population. METHODS: 240 patients with
      ESCC and 198 healthy individuals without overt cancer were chosen as our
      experimental subjects. Information about family address, sex, age, BMI, smoking
      and drinking habits and family history of cancer were collected. Blood samples
      were taken from all subjects and tumor tissues were freshly sampled from resected
      specimens. After DNA was extracted and amplified, the C20orf54 SNPs were
      sequenced by ABI 3730XL in BGI China. Frequencies were then calculated and
      associated with the collected suspicous risk factors. RESULTS: Drinking status, a
      family history of ESCC, blood type and BMI were found to have great influence on
      the risk of developing ESCC. Overall genotype frequencies of the RFT2 SNP 1172
      C>A (rs3746803) and 1246A>G (rs3746802) in ESCC patients are significantly
      different from that in healthy controls (x2=13.10, P=0.001 and x2=7.97, P=0.019,
      respectively). For RFT2 rs3746803, C/T+T/T genotype did not show a relationship
      with the risk of ESCC (the age and gender adjusted OR=0.66, 95% CI=0.41-1.05)
      when using C/C genotype as the reference. For RFT2 rs3746802, the A/G +G/G
      genotype demonstrated a significantly decreased risk to the development of ESCC
      (the age and sex adjusted OR=0.53, 95% CI=0.34-0.84) with A/A as the reference.
      CONCLUSIONS: The present study suggests that the C20orf54 functional SNPs might
      be associated with a risk of ESCC development.

PMID- 22471456
TI  - Human papillomavirus vaccination intention among young women in Thailand.
AB  - AIMS: The aims of this study were to examine knowledge and beliefs regarding HPV
      and cervical cancer and to predict HPV vaccination intention among young women in
      Thailand using a cross-sectional descriptive study design. METHODS: An online
      survey was carried out to obtain young women's demographic, HPV and cervical
      cancer-related health characteristics, knowledge, and beliefs toward HPV and
      cervical cancer of a sample of young women aged 18-24 years (n = 391) recruited
      from universities/colleges located in Chiang Mai, Thailand. Multivariate logistic
      regression analysis was used to determine significant independent predictors of
      HPV vaccination intention. FINDINGS: Five participants (1.2%) had received at
      least one shot of the HPV vaccine. Of 386 participants, 218 (56.5%) reported high
      intention to obtain the HPV vaccine. Young women's knowledge about HPV and
      cervical cancer was moderate, with a mean knowledge score of 7.89 (SD, 3.99;
      range, 0-15). Knowledge was significantly and positively related to perceived
      susceptibility, perceived seriousness, and perceived benefits of HPV vaccination,
      but negatively related to perceived barriers to HPV vaccination. Participants
      with a higher level of knowledge were significantly more likely to obtain the
      vaccine. A multivariate logistic regression model identified predictors of HPV
      vaccination intention: recommendations from significant others, perceived
      susceptibility, perceived benefits, and feeling embarrassed about getting the HPV
      vaccine. CONCLUSIONS: Health education efforts are needed to promote further
      understanding of HPV and cervical cancer, particularly with more attention to HPV
      vaccination.

PMID- 22471457
TI  - Suppressive effects of Moringa oleifera Lam pod against mouse colon
      carcinogenesis induced by azoxymethane and dextran sodium sulfate.
AB  - Moringa oleifera Lam (horseradish tree; tender pod or fruits) is a major
      ingredient in Thai cuisine and has some medicinal properties. Previous studies
      have shown potentially antioxidant, antitumor promoter, anticlastogen and
      anticarcinogen activities both in vitro and in vivo. The present study was
      conducted to investigate chemopreventive effects on azoxymethane (AOM)-initiated
      and dextran sodium sulfate (DSS)-promoted colon carcinogenesis in mice. Male ICR
      mice were divided into 8 groups: Group 1 served as a negative control; Group 2
      received AOM/DSS as a positive control; Groups 3-5 were fed boiled freeze-dried
      M. oleifera (bMO) at 1.5%, 3.0% and 6.0%, respectively supplemented in basal
      diets for 5 weeks; Groups 6-8 were fed with bMO diets at the designed doses above
      for 2 weeks prior to AOM, during and 1 week after DSS administration. At the end
      of the study, colon samples were processed for histopathological examination.
      PCNA indices, and iNOS and COX-2 expression were assessed by
      immunohistochemistry. The results demonstrated the incidences and multiplicities
      of tumors in Groups 6-8 to be decreased when compared to Group 2 in a dose
      dependent manner, but this was significant only in Group 8. The PCNA index was
      also significantly decreased in Group 8 whereas iNOS and COX-2 protein expression
      were significantly decreased in Groups 7 and 8. The findings suggest that M.
      oleifera Lam pod exerts suppressive effects in a colitis-related colon
      carcinogenesis model induced by AOM/DSS and could serve as a chemopreventive
      agent.

PMID- 22471458
TI  - KISS1 expression in osteosarcoma: high in chinese clinical cases, but lower in
      cell lines.
AB  - PURPOSE: Osteosarcoma is the most common primary bone malignancy with a notorious
      feature of high metastasis. KISS1 has been identified as a putative human
      metastasis suppressor gene in numerous types of cancer. This study was aimed to
      evaluate the relationship between expression of KISS1 and invasion ability in
      osteosarcoma cell lines, and the relationships between KISS1 expression levels
      and prognosis of clinical cases. METHODS: Expression levels of KISS1 in 3 types
      of osteosarcoma cell lines (MG-63, Saos-2 and U-2 OS) and a normal osteoblast
      cell line (hF-OB 1.19) were examined using semi-quantitative RT-PCR and
      immunochemistry staining. Transwell assays were used to detect the cell invasion
      ability. The osteosarcoma cell lines and specimen sections of osteosarcoma
      together with control were immuno-stained with KISS1 antibody. The relationship
      between the clinical data and the expression of KISS1 was evaluated. RESULTS:
      KISS1 mRNA expression was moderate in U-2 OS, weak in Saos-2 and lost in MG-63.
      Transwell assays displayed a gradually increased aggressive phenomenon in
      osteosarcoma cell lines U-2 OS, Saos-2 and MG-63. However, a contrary conclusion
      was obtained with clinical specimen, a higher positive rate of KISS1 expression
      being displayed in osteosarcoma patients, especially in metastastic cases,
      compared to the benign osteochondroma patients. Furthermore, significant earlier
      distant metastasis was observed in KISS1 positive than negative cases.
      CONCLUSION: KISS1 expression levels were found to be decreased with the
      increasing aggressive ability in osteosarcoma cell lines. However, expression of
      KISS1 positively correlated with metastasis in osteosarcoma patients.

PMID- 22471459
TI  - Jaceosidin induces p53-dependent G2/M phase arrest in U87 glioblastoma cells.
AB  - Flavonoid compounds have been shown to trigger cell cycle arrest at G0/G1, S and
      G2/M checkpoints, allowing cells to repair DNA damage before entry into mitosis.
      Jaceosidin, a flavonoid compound, has been reported to induce apoptosis in
      various cancer cell lines. In our previous study, we established that jaceosidin
      induces apoptosis in U87 glioblastoma cells through G2/M phase arrest. However
      the molecular mechanisms oremained unclear. In the present study, mRNA and
      protein expression levels of major cell cycle regulatory genes were analyzed by
      semi-quantitative RT-PCR and Western blot studies respectively. The results
      demonstrated that jaceosidin-induced G2/M phase arrest in U87 cells is associated
      with DNA fragmentation, up-regulation of p53 and p21 and subsequent down
      regulation of cyclin B1 and CDK1 expression at mRNA as well as at protein level.
      These findings provide insights into jaceosidin-induced G2/M phase arrest in U87
      glioblastoma cells.

PMID- 22471460
TI  - Lack of associations of polymorphisms of IL-7R, IL-13 and IL-15 with NSCLCs in
      non-smoking Chinese.
AB  - Studies have shown that immune cells play a key role in lung cancer development.
      Five SNPs (rs1494555, rs7737000, rs20541, rs1057972 and rs2857261) are associated
      with lung cancer risk among Caucasians and/or African-Americans, but the
      polymorphisms may be implicated in different susceptibilities for lung cancer
      across different populations because of underlying genetic heterogeneity. We
      therefore conducted a study to examine this relationship in non-smoking Chinese.
      As a result , no significant associations were observed between SNPs and NSCLCs,
      whetehr of squamous cell or adenocarcinoma type. Results indicated polymorphisms
      of IL-7R, IL-13 and IL-15 are not major contributors to NSCLC susceptibility,
      although we can not rule out synergistic effects with cigarette smoke in NSCLC
      development in smoking Chinese.

PMID- 22471461
TI  - Expression of type IV collagen, metalloproteinase-2, metalloproteinase-9 and
      tissue inhibitor of metalloproteinase-1 in laryngeal squamous cell carcinomas.
AB  - OBJECTIVE: To investigate the significance of type IV collagen, metalloproteinase
      2 (MMP-2), metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase
      1 (TIMP-1) expression in laryngeal squamous cell carcinomas (LSCCs). METHODS:
      Expression was quantified in 44 LSCC and 22 adjacent non-cancer normal tissues
      using a streptavidin-peroxidase conjugated immunohistochemistry and associations
      between the levels of the four proteins and clinicopathological characteristics
      in LSCC were analyzed. RESULTS: Significantly different expression of all four
      proteins was observed in LSCC and adjacent non-cancer normal tissues (P<0.05).
      Expression of type IV collagen correlated with primary cancer status (P = 0.04),
      clinical stage (P = 0.04) and histological grade (P = 0.01). Expression of MMP-9
      correlated with the location of the tumor (P = 0.04), cervical node metastasis (P
      = 0.02) and prognosis (P = 0.02). The (MMP-2+MMP-9)/TIMP-1 score was associated
      with the prognosis of LSCC (P < 0.01). CONCLUSIONS: This study suggests that
      expression of type IV collagen and its regulators is strongly associated with the
      development of LSCC. Type IV collagen and MMP-9 may be more valuable than MMP-2
      and TIMP-1 for the evaluation of clinical characteristics. Regulation of type IV
      collagen may contribute to the balance of MMPs and TIMPs in LSCC.

PMID- 22471462
TI  - Evaluating knowledge about human papillomavirus infection among Brazilian health
      professionals.
AB  - Human papillomavirus (HPV) infection is one of the most common sexually
      transmitted diseases worldwide. Although two safe and clinically effective
      vaccines against HPV have been developed, they are not available to the public
      health network in Brazil. This study was performed to assess knowledge about HPV
      among seventy-nine professionals who completed a questionnaire about diagnosis,
      transmission, symptoms, prevention and general information. General knowledge
      about HPV was high, as most of them recognized that HPV is transmitted sexually
      (98.7%), the disease can be asymptomatic (82.3%) or warts can be present on the
      genitals (84.8 ) and the Pap smear is the screening method to identify cellular
      changes on the cervix (88.6%). However, many professionals did not know that
      there are now vaccines available for many HPV variants (38.0%) and that not all
      of them are oncogenic (44.3%). These data show that further educational programs,
      especially about HPV prevention, are needed in Brazil.

PMID- 22471463
TI  - Genetic analysis of liver metastatic cell lines with different metastatic
      potential.
AB  - Metastasis is the major feature of malignant tumors that causes 90% of cancer
      deaths. Our laboratory has already established liver metastatic clones with YCC
      16, isolated from the blood of a gastric cancer patient and expanded in vitro
      culture using a repeated orthotopic implantation method, and had reported
      biologic behaviour of the parental YCC-16, the orthotopic primary S1L0, and S1L1,
      S2L2 and S3L3 liver metastatic clones. Here, using these cell lines, we screened
      from chromosomal abnormalities using karyotype analysis and micro-CGH matching.
      There were 31 genes screened using PCA method which were functionally related to
      cell adhesion. Also, there were 23 genes selected which were related to the liver
      specific metastasis but excluded genes related to adhesion. There were 4 genes
      which demonstrated reduced or increased expression stepwise with passage. In
      conclusion, our results should contribute to exploring the mechanisms of liver
      metastasis by gastric cancer.

PMID- 22471464
TI  - Talin1, a valuable marker for diagnosis and prognostic assessment of human
      hepatocelluar carcinomas.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most lethal and
      prevalent cancers in the human population. Despite its significance, there is
      only limited understanding of pathological mechanisms and therapeutic options.
      Talin1, a focal adhesion complex protein that is required for cell adhesion and
      motility, regulates integrin interactions with extracellular matrix (ECM). In the
      present study, we aimed to study the possible role of Talin1 in diagnosis and
      prognosis of HCC. METHODS: Expression of Talin1 protein was detected in normal
      liver tissues (n=10), HCC tissues (n=32) and adjacent non-cancerous tissues
      (n=32) by immunohistochemistry and real time PCR. RESULTS: While Talin1 was
      observed in all tissues, the protein and mRNA expression of Talin1 in HCC tissues
      was significantly lower than that in the adjacent non-cancerous tissues and
      normal liver tissues(P<0.05). In addition, the expression of Talin1 in HCCs was
      significantly correlated with pathological differentiation, integrity of the
      tumor capsule, portal vein tumor thrombus and tumor size (P<0.05). CONCLUSIONS:
      Talin1 is possibly involved in the process of the carcinogenesis, infiltration
      and metastasis of HCC and has potential as a marker for diagnosis and prognostic
      assessment.

PMID- 22471465
TI  - Evaluation of genotoxic and anti-mutagenic properties of cleistanthin A and
      cleistanthoside A tetraacetate.
AB  - Cleistanthin A (CleinA) and cleistanthoside A (CleisA) isolated from plant
      Phyllanthus taxodiifolius Beille have previously shown potent anticancer effects.
      To promote their medicinal benefits, CleisA was modified to cleistanthoside A
      tetraacetate (CleisTA) and evaluated for genotoxic and anti-mutagenic properties
      in comparison with CleinA. Both compounds showed no significant mutagenic
      activity to S. typhimulium bacteria and no cytotoxic effect to normal mammalian
      cells. The non genotoxic effect of CleinA was further confirmed by un-alteration
      of cytokinesis-block proliferation index (CBPI) and micronucleus (MN) frequency
      assays in Chinese hamster lung fibroblast (V79) cells, and of CleisTA was
      confirmed by un-changes of human peripheral blood lymphocytes (HPBL) chromosomal
      structure assay. Moreover, the metabolic form of CleinA efficiently demonstrated
      cytostasis effect to V79 cell and prevented mutagen induced Salmonella TA98 and
      TA100 reversion, whereas both metabolic and non-metabolic forms of CleisTA
      reduced HPBL mitotic index (%M.I) in a concentration-dependent relationship. The
      results support CleinA and CleisTA as the new lead compounds for anti-cancer drug
      development.

PMID- 22471466
TI  - Clinico-pathological pattern of extranodal non-Hodgkin's lymphoma in Saudi
      Arabia.
AB  - OBJECTIVES: The incidence of primary extranodal non-Hodgkin's lymphoma (NHL) is
      variable in different regions of world but there is a paucity of literature on
      various demographic aspects of extranodal NHL as a group. This study was
      conducted to evaluate the clinico-pathological pattern of extranodal NHL in Saudi
      patients. METHODS: We retrospectively studied a cohort of 855 NHL patients in
      four tertiary care centres in Riyadh, Saudi Arabia over a period of 5 years.
      RESULTS: Extranodal NHL constituted 41.4% of the total. The mean age of affected
      patients was 55?18 years and a male to female ratio of 1.5:1.0. Most presented in
      the age range of 41-60 years. NHL of gastro-intestinal (GI) tract was the most
      common extranodal variety, followed by head and neck NHL (18%), primary cutaneous
      lymphoma (14.4%), primary CNS lymphoma (5.6%), and primary bone, thyroid and soft
      tissue lymphoma (4.5% each). In the GI tract, stomach was the most common site
      involved, accounting for more than 81% of GI NHL. Diffuse large B-cell lymphoma
      was the most common histologic type, comprising around 72% of all extranodal
      lymphomas. CONCLUSIONS: Extranodal NHL is common in Saudi Arabia and diffuse
      large B cell lymphoma is the most common histologic subtype. We found significant
      differences in the pattern of extranodal NHL in Saudi patients compared to those
      reported from other parts of the world. Further studies focused on the risk
      factors and treatment outcome are needed to better understand the biology of a
      disease common in this population.

PMID- 22471467
TI  - Appropriateness of the standard mortality/incidence ratio in evaluation of
      completeness of population-based cancer registry data.
AB  - BACKGROUND: The magnitude of differences in mortality incidence (M:I) ratios
      derived from the national mortality source and those derived from cancer registry
      (CR) databases may be used to determine associated factors. METHODS: All
      information on cancer incidence cases and mortality cases from January 1, 2003 to
      December 31, 2007 were retrieved from 5 population-based cancer registries in
      four regions of Thailand. Two sources of mortality were used: death cases within
      the cancer registries and mortality statistics obtained from the Ministry of
      Public Health (MOPH). Plots of percentage M:I ratios from cancer registry
      databases and from national mortality sources against 1 minus 5 years relative
      survival (1-5yrRS) were used to visualize the correlation between the two
      mortality sources. A Poisson regression model was used to determine the influence
      of cancer sites and registries on the M:I ratio/[1-5yrRS]. RESULTS: There was
      high variability between the standard M:I ratio derived from national mortality
      compared with 1-5 year RS. The factors affecting M:I ratios are sources of
      mortality data and misclassification of topographic site as the cause of death.
      CONCLUSIONS: Use of the M:I ratio is not recommended to evaluate completeness of
      cancer registry data when the quality of mortality data is poor.

PMID- 22471468
TI  - Prognostic significance of the metastatic lymph node ratio in T3 gastric cancer
      patients undergoing total gastrectomy.
AB  - AIMS AND BACKGROUND: The International Union Against Cancer tumor node metastasis
      classification is routinely applied for evaluating the prognosis of patients with
      gastric cancer. However, results are still heterogeneous. This study was
      therefore carried out to evaluate the prognostic significance of the metastatic
      lymph node (LN) ratio in T3 gastric cancer patients undergoing gastrectomy.
      METHODS: Clinical data of 109 LN- positive cases were retrospectively analyzed.
      Spearman correlation analysis was used to determine the correlation coefficiency.
      Survival time was determined by Kaplan-Meier and Log-rank test. Multivariate
      analysis was performed using the Cox model. ROC curves were used to compare the
      accuracy of the number of metastatic LN and metastatic LN ratio. RESULTS: The
      metastatic LN ratio did not correlate with the number of LN when at least 15
      nodes were dissected, whereas the number of metastatic LN did. Univariate
      analysis showed that the metastatic LN ratio influenced significantly the
      survival time, while multivariate analysis revealed it to be a major independent
      prognostic factor. CONCLUSIONS: The metastatic LN ratio can be used as a major
      independent prognostic factor for the patients with T3 gastric cancer.

PMID- 22471469
TI  - Combination of IL-24 and cisplatin inhibits cervical cancer growth in a xenograft
      nude mice model.
AB  - IL-24/mda-7 delivery augments the sensitivity of several tumor types to cisplatin
      but the underlying mechanism(s) are unclear. Here, we used a cervical cancer
      xenograft model in nude mice to further elucidate the interaction between IL-24
      and cisplatin. Nude mice were inoculated subcutaneously in the left axilla with
      Hela cells and randomly grouped into 5 treatment schedules: PBS (I); pDC316
      vector (II); pDC316-hIL-24 (III); cisplatin (IV); and pDC316-hIL-24 combined with
      cisplatin (V). Groups III, IV and V showed significant reduction at mean tumor
      weight by 43%, 50% and 72%, respectively, after 4 weeks in comparison to thePBS
      and vector control groups. Mitotic counts in groups III, IV and V were also
      significantly reduced and expression of tumor suppressor gene nm23-H1 protein was
      significantly higher in groups III and V than in the cisplatin (IV), PBS (1), and
      vector (II) cases. The cisplatin group exhibited significantly greater weight
      loss than the other four groups. The mean weight loss of the combined group,
      while significantly more than in the controls and the IL-24 group, was
      significantly less than that of the cisplatin group. The IL-24 group and the
      combined therapy group exhibited enhancing effects on the tumor suppressor gene
      nm23H1expression.

PMID- 22471470
TI  - Fenugreek, a naturally occurring edible spice, kills MCF-7 human breast cancer
      cells via an apoptotic pathway.
AB  - There is growing use of anticancer complementary and alternative medicines
      worldwide. Trigonella foenum graecum (Fenugreek) is traditionally applied to
      treat disorders such as diabetes, high cholesterol, wounds, inflammation, and
      gastrointestinal ailments. Fenugreek is also reported to have anticancer
      properties due to its active beneficial chemical constituents. The mechanism of
      action of several anticancer drugs is based on their ability to induce apoptosis.
      The objective of the study was to characterize the downstream apoptotic genes
      targeted by FCE in MCF-7 human immortalized breast cells. FCE effectively killed
      MCF-7 cells through induction of apoptosis,confirmed by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) and RT-PCR assays. When cells
      were exposed to 50 MUg/mL FCE for 24 hours, 23.2% apoptotic cells resulted, while
      a 48-hour exposure to 50 MUg/mL caused 73.8% apoptosis. This was associated with
      increased expression of Caspase 3, 8, 9, p53, Fas, FADD, Bax and Bak in a time
      and dose-dependent manner, as determined by real- time quantitative PCR. In
      summary, the induction of apoptosis by FCE is effected by its ability to increase
      the expression of pro-apoptotic genes and the spice holds promise for
      consideration in complementary therapy for breast cancer patients.

PMID- 22471471
TI  - Chemopreventive potential and safety profile of a Curcuma longa extract in women
      with cervical low-grade squamous intraepithelial neoplasia.
AB  - OBJECTIVE: To determine whether Curcuma longa Linn extract, NBFR-03, can arrest
      low-grade squamous intraepithelial neoplasia (LSIL) a 12 week intervention study
      was performed. METHODS: Of a total of 1473 women undergoing Pap smear screening,
      88 cases had LSIL. Only those with persistent LSIL subsequent to antimicrobial
      therapy, and willing to follow the protocol (N=21), were included for clinical
      examination, Pap smears, colposcopy, clinical biochemistry, urinalysis and
      assessment of serum IL-6, being conducted before and after treatment.
      Standardised NBFR-03 (0.2gm) capsules were administered, twice daily, for 12
      weeks. RESULTS: None progressed to higher grade lesion as assessed by Pap smears
      and colposcopy. Sixteen cases regressed to atypia, ASCUS or inflammatory pattern;
      3 persisted as LSIL, 1 discontinued early because of itching, and 1 did not
      start. None developed any significant abnormality clinically or biochemically.
      Micrometry showed a significant reduction in nuclear diameter and
      nucleocytoplasmic ratio after treatment (p<0.02, and <0.05 respectively). Serum
      IL-6 levels showed a significant decline (mean 248? 156 (SEM) vs 27.7? 10.5 (SEM)
      pg/ ml; p<0.05). CONCLUSION: Use of NBFR-03 for 12 weeks was associated with an
      arrest or regression of LSIL in Pap smears and colposcopy, with reduction in the
      circulating IL-6 levels.

PMID- 22471472
TI  - CXCR4 expression in patients with high-risk locally advanced renal cell carcinoma
      can independently predict increased risk of disease progression and poor overall
      survival.
AB  - AIMS AND BACKGROUND: CXC receptor 4 (CXCR4), one of chemokine receptor family,
      plays important roles in metastasis of solid malignancies. In the present study,
      we aimed to investigate the potential predictive value of CXCR4 in the metastasis
      of patients with high-risk locally advanced renal cell carcinoma (LARCC).
      MATERIALS AND METHODS: From 2001 to 2005, the expression of CXCR4 in 117 high
      risk LARCCs was evaluated with immunohistochemical staining and assessed for
      correlations with clinical characteristics, progression-free survival (PFS) and
      overall survival (OS) of the patients. RESULTS: Mean duration of follow-up was 51
      months. 4-year PFS and OS of patients was 55.6% and 69.2%, respectively. High
      expression of CXCR4 was associated with not only increased risk for disease
      progression (p=0.001), but also worse OS of high-risk LARCC patients (p=0.001).
      Further analysis also suggested that CXCR4 expression had a significant negative
      predictive value for the effect of interferon alpha (IFN-alpha) on PFS (p=0.003).
      CONCLUSIONS: CXCR4 is a novel biomarker for prognosis in high-risk LARCC, which
      might furthermore have promise to predict clinical response to adjuvant therapy.

PMID- 22471473
TI  - Increasing incidence of brain and nervous tumours in urban Shanghai, China, 1983
      2007.
AB  - BACKGROUND: Wide use of cellular telephones has given rise to concerns about
      adverse health effects, especially in the brain, which might caused by the low
      power microwave-frequency signal transmitted by the antennas on handsets.
      Subscribers to cellular telephone services increased from mid-1990s in Shanghai;
      time trends in brain and nervous tumour after 2000 may supply information about
      possible associations between tumour risk and cellular telephones use. METHODS:
      We investigated time trends in the incidence of brain and nervous tumour in urban
      Shanghai, from 1983 to 2007, applying joinpoint regression models to analyze the
      annual incidence rates and to predict future trends. RESULTS: from 1983 to 2007,
      the age-adjusted incidence rate of brain and nervous tumours increased gradually
      by 1.2% per year (95% confidence interval [CI] = 0.4% to 1.9%) among men and 2.8%
      per year (95% CI =2.1 to 3.4) among women. Age-adjusted incidences of brain and
      nervous tumours in urban Shanghai for 2020 were estimated to 7.4 and 10.9 per
      100,000 person-years. CONCLUSION: The study did not support an association
      between cellular telephone use and increased risk of brain and nervous tumours.
      However, considering the increasing incidence rate of brain and nervous tumours
      now and in the future, in addition to the high prevalence of mobile phone
      exposure in the population and worldwide, assessment of longer follow-up time
      trends in brain tumour incidence rates is warranted.

PMID- 22471474
TI  - Differences in behavioral outcomes between first-year and second-year
      participants in a community-based colorectal cancer education intervention.
AB  - INTRODUCTION: Colorectal cancer (CRC) is the third most prevalent cancer in
      China, and the fifth most lethal among all cancers. Community-based health
      education is helpful for health planners to promote cancer screening, yet
      relatively few studies tapped the temporal pattern of intervention effectiveness
      in a multiyear CRC education program. Using data from a two-year CRC community
      education, this study was aimed at exploring whether the health education
      intervention effectiveness differs between first-year and the second-year
      participants. METHOD: A two-year health education intervention was carried out in
      four communities in Shanghai, China. The health education focused on raising
      awareness about CRC, the principles of fecal occult blood test (FOBT) screening,
      and instruction about use of the FOBT kit. Local community health service centers
      conducted the lectures once a month. All adult residents were invited to attend
      these lectures. At the end of the first year and the second year, structured in
      person interviews were conducted for the residents who attended the lectures.
      There were 205 enrollees who completed the first-year interviews and 836
      enrollees who completed the second- year interviews. Logistic regression was used
      to compare the attitudinal and behavioral outcomes of enrollees in years 1 and 2.
      RESULT: Of the 1041 respondents, 24.5% had received FOBT during the program
      period, while 12% had received colonoscopy check, both substantially higher than
      the background screening rate in Shanghai. Respondents in year 2 were less
      willing to take FOBT than those in year 1 (O.R.=0.618, p<0.01), but there was no
      significant difference in terms of willingness to take colonoscopy after
      adjustment for covariates in logistic regression. Multiple logistic regression
      also showed that respondents in year 2 were significantly less likely to take
      FOBT than those in year 1 (O.R. = 0.263, p<0.01) and a similar tendency was noted
      for colonoscopy (O.R.=0.600, p=0.074). CONCLUSION: The CRC screening rate after
      the health education compared favorably with the background screening rate, yet
      the decline in screening rate in year 2 indicates that further study is needed to
      understand the determinants of intervention effectiveness.

PMID- 22471475
TI  - Pharmacodynamics of fish oil: protective effects against prostate cancer in TRAMP
      mice fed with a high fat western diet.
AB  - Numerous epidemiological studies suggest that frequent consumption of fish would
      decrease certain major inflammatory-related chronic diseases including cancer.
      AIMS: To investigate the cancer chemoprotective effect of fish oil (FO) in
      Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice fed a FO diet (10%
      Menhaden fish oil; FO group) versus a 20% high fat diet (HF group; typical of a
      Western diet), both with a total content of 20% fat and equal calories. METHODS:
      For each diet, two experimental arms were performed. The mice were put on diet at
      8th or 12th week of age for periods of 14 and 10 weeks, the experiments being
      terminated when the mice reached 22 weeks of age. The animals were monitored
      weekly for health, and upon necropsy were examined for whole body metastasis, and
      prostate tissues were confirmed with histopathology. RESULTS: At the end of the
      study, the FO group had significantly reduced prostate tumor weight (p<0.05)
      compared to the HF group. The incidence of palpable tumors and carcinomas was
      also lowered. Finally, there was no metastasis found in the FO group, whereas in
      the HF group, 16.7% of the mice were found to have metastases. CONCLUSIONS: This
      is the first study showing the beneficial effects of FO against prostate cancer
      having a HF diet, suggesting potential beneficial effects of FO in humans
      consuming HF in their diet.

PMID- 22471476
TI  - Clinicopathologic evaluation of subgroups of diffuse large B cell lymphoma by
      immunohistochemistry.
AB  - Diffuse large B cell lymphoma (DLBCL) has become an emerging epidemic in recent
      years. Striking heterogeneity in its clinical, biological and treatment responses
      prompted us to identify variation in our study group. The aim was to classify the
      DLBCL into prognosis-based subgroups according to the WHO classification and to
      evaluate their relation to clinical parameters (age, gender, anatomic location
      and B symptoms), as well as bcl 2 and Ki 67 status. PATIENTS AND METHODS: A cross
      sectional study was carried out on 42 DLBCL patients, classified histologically
      and immunophenotypically into germinal center B cell like (GCB) or non-GCB type.
      Immunohistochemistry (IHC) was performed using antibodies against CD 10, MUM-1
      and bcl 6; additionally anti-apoptotic protein bcl 2 and proliferative marker Ki
      67 (using cutoff value of 70%) were also assayed by IHC. RESULTS: Of the total
      27/42 (64%) were males and 15/42 (36%) females, with a mean age of 44.1?15 years.
      15/42 (36%) cases were of GCB type as compared to 27/42 (64%) of non GCB type.
      Extranodal involvement and B symptoms were seen in 18/27 (66.6%) and 20/27(74%)
      of the non GCB type, whereas bcl 2 protein expression and Ki 67 proliferative
      index (PI) <70% were each noted in 22/27 (81.4%). CONCLUSION: We document an
      astonishingly high number of non-GCB type DLBCL in our population. It is alarming
      to see such an aggressive tumor proliferating in our region. Significant
      association of non-GCB type with extranodal origin, B symptoms and low Ki 67 PI
      (<70%) is another concern.

PMID- 22471477
TI  - Multivariate survival and outcome analysis of 154 patients with gastric cancer at
      a single Chinese institution.
AB  - This study was conducted to analyze and elucidate key prognostic factors for
      gastric cancer (GC), and to understand the current status of GC diagnosis and
      treatment in Hubei Province, China. Major clinical and pathological information
      on 154 GC patients was retrospectively collected, including gender, age, tumor
      site, surgical approach, histological type, TNM stage and chemotherapy cycles.
      Overall survival (OS) was analyzed in relation to these factors. The median OS
      was 12.0 months (0.5-69.0 months), and 1-, 2-, 3- and 5-year survival rates were
      53.0%, 23.0%, 8.0% and 1.0%, respectively. The median OS by TNM stage was 21.0
      months for stages I+II and 11.5 months in stages III+IV (P=0.043), and 1-, 2-, 3-
      and 5-year survival rates were 72.0% vs 50.0%, 40.0% vs 19.0%, 16.0% vs 6.0% and
      0% vs 1.0 %, respectively. The median OS by chemotherapy cycles was 18.0 months
      in chemotherapy >=6 cycles group and 11.0 months in chemotherapy <6 cycles group
      (P=0.009), and 1-, 2-, 3- and 5-year survival rates were 68.0% vs 49.0%, 41.0% vs
      18.0%, 12.0% vs 7.0% and 0% vs 1.0%, respectively. Multivariate analysis
      identified tumor site, surgical approach and chemotherapy cycles as independent
      predictors for improved survival. Implementation of standardized radical surgery
      and reasonable adjuvant therapy could improve survival and prognosis of GC
      patients.

PMID- 22471478
TI  - Special malignancy pattern in Chinese renal transplantation recipients: a single
      center experience and literature review.
AB  - Malignancy is one of the main complications after renal transplantation but the
      situation in Chinese renal allograft recipients remains an enigma. We therefore
      reviewed 1,000 (8,531 person-years follow-up) renal allograft recipients from
      Jinling Hospital, Nanjing University, revealing an incidence rate of 2.4% of post
      transplant malignancies, with a standardized incidence ratio (SIR) of 17.8 (95%
      C.I.: 16.7-18.8); the standardized rate is 1.67%, compared with 0.29% in the
      general population. However, our group demonstrated an extremely low incidence of
      skin cancer, which dominates in western countries. To confirm the findings, we
      reviewed the literature on post-transplant malignancies in Chinese renal
      allograft recipients, covering 296 malignancies in 18,548 renal transplant
      recipients in 21 reports. The top three most common sites of malignancies were
      the digestive tract, bladder and liver. The incidence of skin cancer was very low
      in most centers. These data show that Chinese renal allograft recipients have a
      unique spectrum of post-transplant malignancies, with an extremely very low
      incidence of skin cancer as compared to populations from western countries.

PMID- 22471479
TI  - Transfer of clinical breast examination skills to female community health
      volunteers in Nepal.
AB  - OBJECTIVE: To observe skill transfer for detection of clinical abnormalities in
      the breast by determining kappa agreement, sensitivity, specificity, positive
      predictive value and negative predictive value of clinical breast examination by
      female community health workers (FCHVs) considering surgeon findings as the gold
      standard. METHOD: This cross-sectional study was conducted in Dharan
      Municipality, Eastern Nepal for period of one year from June 2008 to May 2009. A
      total of 1,238 women were examined by both a FCHV and the surgeon. RESULT: The
      interobserver kappa agreement for the detection of clinical abnormalities in
      breast was 67% indicating a good agreement. Sensitivity, specificity, positive
      predictive value and negative predictive values of "FCHVs' clinical breast
      examination" to detect clinical abnormalities in breast in comparison to the
      surgeon's were 70%, 95%, 74% and 94% respectively. CONCLUSION: In view of good
      clinical breast examination skill transfer to FCHVs for detection of clinical
      abnormalities in breast, we conclude effective training of FCHVs may be a feasble
      approach for diagnosis of breast abnormalities in rural Nepal.

PMID- 22471480
TI  - Glutathione S-transferase polymorphisms and bone tumor risk in China.
AB  - AIM: We aimed to study the potential role of GSTM1 and GSTT1 in the risk of
      osteosarcoma in Chinese population. METHODS: We collected 110 osteosarcomas by
      pathologic examination and 226 controls from the First Affiliated Hospital of
      Harbin Medical University during December 2008 to December 2010. Genotyping was
      based upon duplex polymerase-chain-reaction with the PCR-CTPP method. RESULTS:
      Individuals carrying null GSTM1 and GSTT1 had 1.50 and 2.07 fold risks of
      osteosarcoma when compared with non-null genotypes, respectively. The increased
      risk associated with the GSTT1 polymorphism seemed more evident among males (Null
      GSTT1 genotype vs. non-null genotype, adjusted OR= 2.43, 95% CI: 1.29-3.30) than
      females (adjusted OR =1.66, 95% CI: 1.02-2.78). The increased risk was also more
      evident among individuals aged 15 years or less (adjusted OR for null GSTT1
      genotype vs. non-null genotype = 2.24, 95% CI: 1.20-3.24) than those aged more
      than 15 years (adjusted OR = 1.82, 95% CI: 1.07-2.95). CONCLUSION: Our study of
      the association between polymorphisms in GSTM1 and GSTTI and the risk of
      osteosarcoma in a Chinese population provided evidence that null GSTTI might be a
      useful marker of susceptibility to osteosarcoma development, especially for male
      sand young age individuals.

PMID- 22471481
TI  - Increased expression of IL-6 mRNA in hepatocellular carcinoma cell lines
      correlates with biological characteristics.
AB  - BACKGROUND AND AIMS: IL-6 has been implicated in both virus-associated and
      diethylnitrosamine-induced hepatocellular carcinomas (HCCs). Generally it is
      produced by immune cells such as Kupffer cells in the liver. To understand
      mechanisms by which IL-6 might participate in the genesis of HCCs, the production
      of IL-6 by cell lines under different conditions was examined to determine
      inducing factors. METHODS: Expression of IL-6 mRNA in both hepatoma cell lines
      and a normal liver cell line L-02 was measured by quantitative RT-PCR. Biological
      molecules including liposome, dsRNA and cell debris were used to stimulate IL-6
      mRNA expression in HepG2 cells and inhibition was effected by RNAi. Proliferation
      was assessed by MTT and clone formation and migration was determined by scratch
      assay. RESULTS: All of the HCC cell lines observed expressed IL-6 mRNA, including
      HepG2, Bel-7402(7402), MHCC-97H and SMMC-7721.Normal liver cell line L-02 also
      expressed IL-6 mRNA. SiRNA to IL-6 specifically knockdowned IL-6 mRNA expression
      in HepG2, and liposome, dsRNA and cell debris increased it. Both proliferation
      and migration of HepG2 cells were related to the level of IL-6 HepG2 expressed.
      CONCLUSION: Both normal liver cell line and HCC cell lines can produce IL-6 so
      that Kupffer cells are noit the only source of the cytokine in the liver well as
      other immune cells. That the fact that HCC cells reacted to stimulation of
      biological molecules such as liposome, dsRNA or cell debris with increasing
      production of IL-6 indicates that the cytokine might play an important role not
      only in the period of tumor initiation but progression and recurrence as well.

PMID- 22471482
TI  - Platelet-derived growth factor-D promotes ovarian cancer invasion by regulating
      matrix metalloproteinases 2 and 9.
AB  - OBJECTIVE: Platelet-derived growth factor-D (PDGF-D) can enhance invasion and
      metastasis in several human malignancies, though little is known about its
      functions in ovarian cancer. METHODS: In this study, we detected expression of
      PDGF-D in ovarian cancer tissues and cell lines by qRT-PCR, immunohistochemistry
      and western blotting, investigating the influences on cellular proliferation,
      invasion and apoptosis by upregulating its expression. RESULTS: 79.5% (62/78) of
      ovarian cancer samples proved to be PDGF-D positive, in contrast to just
      38.5%(30/78) in their adjacent non-cancer tissues (p<0.001). Moreover, we found
      high levels of PDGF-D were correlated with lymph node metastasis (p=0.025) and
      positive cancer cells in abdominal washings/ascites (p=0.042). In vitro,
      upregulation of PDGF-D enhanced the invasiveness of SKOV3 cells (p<0.01), but had
      no impact on cellular proliferation or apoptosis. Furthermore, expression of
      matrix metalloproteinases 2/9 (MMP2 and MMP9) was positively related with PDGF-D,
      indicating their involvement in the invasion and metastasis of ovarian cancer.
      CONCLUSIONS: Our findings proved that PDGF-D could promote ovarian cancer
      invasion by upregulating MMPs, which might be a potential target for ovarian
      cancer treatment.

PMID- 22471483
TI  - Heparanase antisense suppression of A-549 lung carcinoma invasion.
AB  - OBJECTIVE: Heparanase (HPSE), as the only enzyme which can degrade the
      extracellular matrix and heparin sulfate in basement membrane, plays an important
      role in invasion and metastasis of tumor cells. In this study, we evaluated the
      inhibitory effect of HPSE antisense oligoxydeonucleotide (ASODN) on lung
      carcinoma cell line A-549 invasion. METHODS: Liposome-mediated ASODN was
      transfected into A-549 cells and expression of HPSE protein and mRNA were
      detected by flow cytometry and RT-PCR techniques. Matrigel invasion assays were
      employed to assess effects on invasiveness. RESULTS: Lower expression of HPSE
      protein and mRNA and lower invasive ability to recombinate basal membrane were
      apparent after ASOND treatment (P<0.01). The inhibition rates of cell
      invasiveness were 55.6%, 82.3% and 91.2% treated by ASODN at final concentrations
      of 100, 200 and 400nmol/L, respectively. CONCLUSIONS: HPSE ASODN can downregulate
      the expression of HPSE protein and mRNA in the A-549 cell line and can obviously
      inhibit its invasive ability in a dose-dependent manner in vitro.

PMID- 22471484
TI  - Relationships between epidemiological features and tumor characteristics of
      breast cancer.
AB  - OBJECTIVES: Breast cancer is a histological, morphological and molecular
      heterogenous disease. Like clinical outcomes and prognoses of different subtypes,
      etiologies might also be different. Therefore, epidemiologic risk factors like
      sociologic, demographic, antropometric, reproductive, and menstrual factors can
      be considered as an entity reflected in tumor features. This study was planned to
      explore the relation between well known risk factors of breast cancer and
      histological and molecular features of the tumor. MATERIALS AND METHODS:
      Epidemiologic data for 250 breast cancer patients followed-up by our clinic and
      250 healthy individuals without any diagnosis of malignancy were obtained. The
      data displaying a relation to breast cancer are age, height, weight, body mass
      index (BMI), place of birth and province, educational level, menstrual status,
      age of menarche and menopause, number of births, age at first childbirth, family
      history of breast cancer, history of smoking and hormone treatment, mammographic
      screening, and presence of benign lesions. The tumor characteristics of patients
      in the breast cancer group were recorded. RESULTS: Advanced age, nulliparity, low
      educational level, irregular mammographic screening, early menarche and late
      menopause, and high BMI in postmenopausal period were found to be related to
      increased breast cancer risk. Striking results in terms of the relation between
      epidemiological factors and tumor features were the early diagnosis of breast
      cancer in patients with regular mammographic screening. Tumor size was decreased
      with increased age and increased with increased BMI. Advanced age, prolonged
      lactation, increased number of births, and high education level were found to
      decrease axillary involvement. CONCLUSIONS: Multiparity still continues to be the
      strongest protective factor against breast cancer in our society. The decrease in
      menarche age may be an early sign of the increased breast cancer incidence. Women
      should be informed about the relation between postmenopausal obesity and breast
      cancer and encouraged to attend physical activity and exercise programmes.
      Regular physical examination and mammographic screening are protective against
      breast cancer.

PMID- 22471485
TI  - Immunophenotypic patterns of childhood acute leukemias in Indonesia.
AB  - BACKGROUND: Immunophenotyping, as suggested by WHO, may improve diagnosis of
      childhood leukemia since it offers a better classification of the hematopoietic
      lineage of malignant cells as compared to morphology. Therefore, we aimed to
      determine the proportion of the immunophenotypic subtypes of acute leukemia in
      Indonesian children. METHODS: Samples were obtained from patients (0-14 years of
      age) in 4 hospitals in Indonesia. We analyzed 541 suspected leukemia samples
      presented over a 4-year period (March 2006 - July 2010) by flow cytometry.
      Immunophenotyping allowed classification into acute myeloid leukemia (AML) and
      ALL (B-lineage and T-lineage ALL). RESULTS: Of 541 samples, 136 were tested using
      a single color method and 405 with a three-color method. Concordance with
      morphology was very good (?=0.82) using the three-color method with a panel of 15
      monoclonal antibodies (n=387). A relatively high percentage of acute leukemia was
      classified as AML (23%). Of the ALL samples 83% were B-lineage ALL and 17% T-
      lineage ALL. Nine out of 239 morphological ALL were labeled AML, and 12/79
      morphological AML were in fact ALL. CONCLUSION: Immunophenotyping in a multi
      center study proved feasible and appears particularly important for prognostic
      assessment of childhood leukemia in low income countries such as Indonesia.

PMID- 22471486
TI  - Reliability and validity of the Turkish version of the Memorial Symptom
      Assessment Scale in cancer patients.
AB  - AIM: The Memorial Symptom Assessment Scale (MSAS) is a multidimensional tool
      developed to evaluate measure the prevalence, characteristics and distress of
      common symptoms related to cancer. A validated Turkish version has now become
      available. The aim of this study was to evaluate its reliability and validity.
      METHODS: One hundred-twenty patients were included into this study. The MSAS, The
      Rotterdam Symptom Checklist (RSCL), and Karnofsky Performance Status Scale (KPSS)
      were used for data collection. Content and criterion validities were examined.
      Reliability analyses of the MSAS were performed using internal consistency
      reliability and test-retest reliability. RESULTS: The most frequently reported
      symptom (90%) was problems with sexual interest or activity. Item-total
      correlations ranged between 0.03 and 0.64. There was a high correlation between
      total MSAS and the RSCL (r=0.875, p<0.01). The internal consistency reliabilities
      of subscales of the MSAS and total MSAS were moderately high, with Cronbach alpha
      coefficients ranging from 0.71 to 0.84. The MSAS's test - re-test reliability was
      0.78. CONCLUSION: The MSAS for cancer patients was determined to be a valid and
      reliable instrument for the use in the Turkish population. It is recommended that
      the MSAS-Turkish version can be used as a tool for comprehensive symptom
      assessment in planning nursing care for cancer patients.

PMID- 22471487
TI  - Breast cancer coverage in the media in malaysia: a qualitative content analysis
      of star newspaper articles.
AB  - BACKGROUND: The media play big roles in the public understanding of many health
      issues, and the information relayed to the public through the media clearly
      influences behavior. OBJECTIVES: The objectives of this study were to determine
      whether the content of articles on breast cancer in women published in the Star
      newspaper in 1997 differed from that of those published in 2007 and also to
      determine what factors may have caused any differences. METHODOLOGY: About 45
      articles were identified for the year 1997 and 97 from the year 2007. Copies of
      the articles were obtained through the Star newspaper library. All the articles
      were read an initial time. The final sample for analysis consisted of 18
      newspaper articles published in 1997 and 79 in 2007. Once data collection sheets
      were completed for all articles, the data were transferred to two spreadsheets
      and analyzed manually. RESULTS: Living with breast cancer was the main theme of
      many articles in both years. Family history was emphasized as a risk factor in
      articles from 2007, while an inappropriate bra, electrical power lines, stress,
      smoking and alcohol were emphasized in 1997 as risk factors. In general, articles
      in 2007 focused on overall health practices, especially exercise, while in 1997,
      mammography was considered as the dominant prevention method. CONCLUSION: The
      content of the articles on breast cancer that were published in the Star
      newspaper in Malaysia in 1997 totally differed from that of those published in
      2007. The differences seem to reflect social, political, and scientific
      occurrences over the period studied.

PMID- 22471488
TI  - CA916798 regulates multidrug resistance of lung cancer cells.
AB  - OBJECTIVES: Multidrug resistance (MDR) significantly reduces the efficacy of
      chemotherapy for lung cancer. In this study, we characterized the significance of
      CA916798, a gene up-regulated in cis-dichlorodiamine platinum (CDDP)-resistant
      lung adenocarcinoma cells, in mediating MDR in lung cancer cells. METHODS:
      CA916798 was stably transfected into H446 cells with low endogenous expression of
      CA916798, and knocked down in A549/CDDP cells with high endogenous level of
      CA916798. Expression was confirmed by real-time PCR, Western immunoblotting and
      immunocytochemistry. Subsequent effects were examined on cellular growth,
      apoptosis and cell cycle progression. RESULTS: Ectopic expression of CA916798 in
      H446 cells confered enhanced resistance to multiple chemotherapeutic agents,
      while its reduction rendered A549/CDDP cells less resistant to chemotherapeutic
      agents tested. Further analysis revealed that CA916798 regulates CDDP-induced
      cell growth, apoptosis and cell cycle progression. CONCLUSION: CA916798 may be a
      novel MDR-related target for lung cancer therapy.

PMID- 22471489
TI  - Serum trace element levels in patients with bladder cancer.
AB  - Trace elements are essential components of biological structures, but they can be
      toxic at concentrations beyond those necessary for their biological functions. In
      the present study, groups of 35 patients with bladder cancer and 34 healthy
      volunteer controls were measured for trace elements using a furnace atomic
      absorption spectrophotometer. Serum levels of Cd, Ni and Co were increased
      (p<0.05) and Mn and Zn were decreased (p<0.05) in patients with bladder cancer.
      In the present study, a relationship was seen between the level of trace elements
      and the occurrence of bladder cancer, suggesting that an increase in the serum
      level of Cd, Ni, Co and a decrease in the levels of Zn and Mn might be important
      causes of bladder cancer occurrence; however, defining such a cause-and-effect
      relationship needs several prospective studies to be done, which seems necessary
      with regard to the high prevalence of this cancer.

PMID- 22471490
TI  - Sevoflurane inhibits proliferation, induces apoptosis, and blocks cell cycle
      progression of lung carcinoma cells.
AB  - PURPOSE: Sevoflurane, an inhalational anesthetic, is used extensively during lung
      cancer surgery. However, the effect of sevoflurane on growth of lung carcinoma
      cells remains unclear. The purpose of this study is to investigate effects on
      proliferation, apoptosis, and cell cycling in the A549 human lung adenocarcinoma
      cell line. METHODS: A549 cells were treated with 1.7%, 3.4%, and 5.1 %
      sevoflurane for 2, 4, and 6 hours. Cell proliferation was evaluated by the MTT
      assay and colony formation assay. Apoptosis and cell cycle was analyzed by flow
      cytometry. Expression of X-linked inhibitor of apoptosis protein (XIAP),
      survivin, Bcl-2, Bax, caspase-3, cyclin A, cyclin B1, and cdc2 was measured by
      Western blotting. RESULTS: Significant inhibition of cell proliferation and
      induction of apoptosis were found in A549 cells after sevoflurane treatment.
      Simultaneously, expression of XIAP and survivin was supressed, while that of
      caspase-3 increased significantly, but Bcl-2 and Bax were not altered.
      Sevoflurane caused cell cycle arrest at the G2/M phase. At the same time, data
      revealed that cyclin A, cyclin B1, and cdc2 expression was down-regulated after
      sevoflurane treatment. CONCLUSION: This study demonstrated that sevoflurane
      inhibited proliferation, and induced apoptosis in human lung adenocarcinoma A549
      cells, associated with down-regulated expression of XIAP and suvivin, and
      activating caspase-3.

PMID- 22471491
TI  - Glutathione S-transferase gene polymorphisms and risk of gastric cancer in a
      Chinese population.
AB  - AIM: The potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in risk of
      gastric cancer in Chinese was studied. METHODS: We collected 194 gastric cancers
      by pathologic examination and 412 controls from southern China during January
      2007 to January 2011. Genotyping was based upon duplex polymerase-chain-reaction
      with the PCR-CTPP method. RESULTS: Individuals carrying null GSTM1 and GSTT1 had
      1.49 and 1.96 fold risk sof gastric cancer when compared with respective non-null
      genotypes. We also found a non-significant 37% excess risk of gastric cancer
      among carriers of GSTP1 1b/1b genotype when compared with 1a/1a genotype
      (OR=1.37, 95% CI=0.81-2.25). The combination of null/null GSTM1 and GSTT1
      genotypes showed higher increased risk of gastric cancer (OR=3.17, 95% CI=1.68
      4.21). Moreover, cancers in ever smokers and ever drinkers were observed to be
      strongly associated with null GSTM1 and GSTT1, and a significant cancer risk was
      observed in positive H.pylori infection individuals with null GSTT1. CONCLUSION:
      Our study provided evidence that genetic deletion of GSTM1 and GSTT1 may
      contribute to increased susceptibility to gastric cancer in our Chinese
      population, while the GSTP1a/b polymorphism may not.

PMID- 22471492
TI  - Lack of association between the 8-oxoguanine DNA glycosylase gene Ser326Cys
      polymorphism and gastric cancer: evidence from a meta-analysis.
AB  - OBJECTIVE: To evaluate the association of 8-oxoguanine DNA glycosylase gene
      (OGG1) Ser326Cys polymorphism with gastric cancer via a comprehensive meta
      analysis. METHODS: A total of 12 publications were identified before January 20,
      2011 including 1,390 cases and 3,299 controls. A random-effects model was applied
      irrespective of between-study heterogeneity. Data and study quality were assessed
      in duplicate. RESULTS: No significant association was found for either allele or
      genotype with gastric cancer (odds ratio [OR]=0.96; 95% confidence interval [95%
      CI]: 0.82-1.13; P=0.66), and this was also the case after combining 326Ser/Cys
      and 326Ser/Ser genotypes together (OR=0.87; 95% CI: 0.63-1.20; P=0.40), or
      326Cys/Cys and 326Ser/Cys together (OR=1.03; 95% CI: 0.87-1.22; P=0.72). Subgroup
      analysis by ethnicity indicated that comparison of allele 326Ser versus 326Cys
      generated a weakly and non-significant protective effect on gastric cancer in
      Asians (OR=0.90; 95% CI: 0.75-1.09; P=0.29) and Turks (OR=0.65; 95% CI: 0.37
      1.14; P=0.13), but a non-significant risk effect in Europeans (OR=1.10; 95% CI:
      0.78-1.54; P=0.60) and Brazilians (OR=1.13; 95% CI: 0.81-1.58; P=0.48). No
      publication bias was observed. CONCLUSIONS: Our results collectively suggest that
      the OGG1 Ser326Cys polymorphism might not be a potential candidate risk factor
      for the development of gastric cancer.

PMID- 22471493
TI  - Inhibition of invasion and metastasis of gastric cancer cells through snail
      targeting artificial microRNA interference.
AB  - The zinc-finger factor Snai1 plays an important role in the down-regulation of E
      cadherin expression and in the induction of epithelial-mesenchymal transition
      (EMT) during cancer progression. In gastric cancer tissues, we noted that Snail
      is abnormally high expressed and is remarkably associated with the lymph node
      metastasis. Using a plasmid containing newly synthesized artificial microRNA
      (amiRNA), we transfected gastric cancer cells to block Snail expression. Both
      Snail protein and mRNA levels were significantly decreased in stably transfected
      cells, while protein and mRNA expression of E-cadherin was up-regulated. In
      addition, migration and invasion potential were significantly decreased after
      knockdown of Snail.

PMID- 22471494
TI  - Value of colposcopy in the early diagnosis of cervical cancer in patients with
      abnormal pap smears at Shahid Sadoughi hospital, Yazd.
AB  - BACKGROUND AND OBJECTIVES: Cervical cancer is preventable, although it is common
      in developing countries and Iran, where there is no defined approach to "atypical
      squamous cells of undetermined significance" (ASCUS) on Pap smears. This study
      determined the value of colposcopy in the early diagnosis of cervix cancer in
      females with ASCUS. MATERIALS AND METHODS: This accuracy study examined 213 ASCUS
      cases referred from different cities from 2007 to 2009. All patients underwent a
      repeated conventional Pap smear, colposcopy, endocervical curettage, and a
      cervical biopsy, considered the gold-standard diagnostic test. RESULTS: There was
      no significant relationship between age, age of first intercourse, smoking, or
      number of children and a positive cervical biopsy. The sensitivity and
      specificity of a repeat Pap smear for ASCUS were 15 and 93%, respectively, while
      the respective values for diagnosing cervical cancer with colposcopy were 80 and
      80%. Endocervical curettage had 64% sensitivity and 100% specificity for
      diagnosing cervical cancer, and 11 positive neoplastic or malignant lesions
      reported on endocervical curettage were confirmed by biopsy. DISCUSSION: Based on
      the low accuracy of the Pap smear in Iran as a developing country and the need
      for an early diagnosis of cervical cancer, a cervical biopsy and colposcopy are
      recommended for these patients. Colposcopy and endocervical curettage alone are
      better diagnostic tools than a repeat Pap smear for unsatisfactory Pap smears.

PMID- 22471495
TI  - Cancer morbidity among methyl isocyanate exposed long- term survivors and their
      offspring: a hospital-based five year descriptive study (2006 - 2011) and future
      directions to predict cancer risk in the affected population.
AB  - The purpose of this study was to update both researchers and clinicians about the
      cancer incidence in methyl isocyanate (MIC) exposed long-term survivors and in
      their offspring, focusing on the etiological plausibility. In the time period
      2006-2011, cancer morbidity was evaluated in the population surviving after
      exposure to (MIC) on December 3rd, 1984, in Bhopal. This descriptive study is
      based on hospital registration of 1261 cancer patients those are MIC gas victims
      and their subsequently born offspring. Morbidity status was studied on the basis
      of gender, age, organ and site with relative percentages. Cancers on specific
      sites, with special reference to breast (n=231) (18.31%), lung (n=103) (8.16%),
      tongue (n=103) (8.16%), buccal mucosa (n=94) (7.45%), cervix (n=72) (5.70%), and
      esophagus (n=68) (5.39%) were found in high proportions. Ovary (n=43) (3.40%),
      brain (n=42) (3.33%), larynx (n=40) (3.17%), non-Hodgkin's (n=31) (2.45%),
      gallbladder (n=29) (2.29%), stomach (n=28) (2.22%), head and neck (n=28) (2.22%),
      liver (n=27) (2.14%), acute lymphoid leukemia (n=24) (1.90%), rectum (n=20)
      (1.58%), colon (n=20) (1.58%), chronic myeloid leukemia (n=17) (1.34%), alveolus
      (n=17) (1.34%), Hodgkin's (n=14) (1.11%), uterus (n=14) (1.11%), multiple myeloma
      (n=14) (1.11%), and prostate (n=11) (0.87%) lesions were observed less
      frequently. Remarkably, gradual increase of cancers on different organs and sites
      were observed in the long- term survivors and their offspring. The present study
      observed some cancers which were not previously reported in this population. In
      addition, we also present the future research directions with systematic
      approaches to predict cancer risk in long-term survivors and their future
      generations. On the basis of this morbidity report, we suggest the need of
      biological surveillance through immune system biomonitoring and cytogenetic
      screening to predict the cancer risk in the MIC exposed population and their
      offspring.

PMID- 22471496
TI  - Frequent incidence of double minute chromosomes in cancers, with special up-to
      date reference to leukemia.
AB  - Double minute chromosomes (DMs) are small chromatin bodies consisting of gene
      amplification in an extrachromosomal location. Although found in an variety of
      human tumor cells, their presence in hematologic malignancies is rare and their
      role in leukemogenesis is controversial. However, they are thought to be involved
      in tumorigenesis and in drug resistance, representing a mechanism for upregulated
      oncogene expression generally associated with a poor prognosis. The presence of
      DMs has been associated with a rapid disease course, low response rate, and short
      survival. Little knowledge is, however, available on DMs in leukemias. To
      elucidate this issue, a web-based search for all types of articles published was
      initiated using MEDLINE/PubMed, the Mitelman database and other pertinent
      references on websites. We found that DMs have the highest frequency in adrenal
      carcinoma (28.6%), and lowest rate noted as 2.6% for large intestine. The large
      Mitelman database and other web based pertinent reports provide novel knowledge
      of DMs and their association in the wide field of cancers.

PMID- 22471497
TI  - HADHA is a potential predictor of response to platinum-based chemotherapy for
      lung cancer.
AB  - To identify a cisplatin resistance predictor to reduce or prevent unnecessary
      side effects, we firstly established four cisplatin-resistant sub-lines and
      compared their protein profiles with cisplatin-sensitive parent lung cancer cell
      lines using two-dimensional gel electrophoresis. Between the cisplatin-resistant
      and -sensitive cells, a total of 359 protein spots were differently expressed
      (>1.5 fold), and 217 proteins (83.0%) were identified. We focused on a
      mitochondrial protein, hydroxyl-coenzyme A dehydrogenase/3-ketoacyl-coenzyme A
      thiolase/enoyl-coenzyme A hydratase alpha subunit (HADHA), which was increased in
      all cisplatin-resistant cells. Furthermore, pre- treated biopsy specimens taken
      from patients who showed resistance to platinum-based treatment showed a
      significantly higher positive rate for HADHA in all cases (p=0.00367), including
      non-small cell lung carcinomas (p=0.002), small-cell lung carcinomas (p=0.038),
      and adenocarcinomas (p=0.008). These results suggest that the expression of HADHA
      may be a useful marker to predict resistance to platinum-based chemotherapy in
      patients with lung cancer.

PMID- 22471498
TI  - Cisplatin induces apoptosis via upregulating Wrap53 in U-2OS osteosarcoma cells.
AB  - Wrap531alpha, a newly identified natural antisense transcript of p53, can
      regulate p53 expression upon DNA damage. We sought to investigate changes in
      Wrap53 and p53 levels in an osteosarcoma cell line (U-2OS) exposed to cisplatin
      and to study apoptosis before and after knockdown of Wrap53. Our RT-PCR analysis
      showed a dose- dependent 3 to 40-fold increase in Wrap53 mRNA transcript levels
      in U-2OS exposed to 5 to 20 MUM cisplatin. An approximate 2-fold increase was
      also observed in transcript levels of p53 mRNA. Furthermore, transient knockdown
      of Wrap53 by siRNAs in U-2OS cells treated with 10 MUM cisplatin reduced p53 mRNA
      transcript levels by up to 50% of those of controls. Immunoblotting analysis
      showed that in U-2OS cells treated with siRNA against exon 4 of the Wrap53 gene,
      the protein level of p53 was also markedly reduced. Our findings suggest that
      cisplatin upregulates the expression of p53 in osteosarcoma cells by upregulating
      the transcript levels of Wrap53. Finally, measurement of apoptotic cell death by
      flow cytometry showed that knockdown of Wrap53 reduced apotosis in U-2OS cells
      induced by cisplatin.

PMID- 22471499
TI  - Altered serum levels of elements in acute leukemia cases in Turkey.
AB  - OBJECTIVE: The purpose of the study was to compare serum concentrations of some
      elements [zinc (Zn), copper (Cu), manganese (Mn), magnesium (Mg), lead (Pb), iron
      (Fe), cadmium (Cd) and cobalt (Co)] in acute leukemia patients with those of
      healthy subjects. METHODS: The study group consisted of newly diagnosed acute
      leukemia patients and the controls were matched for socioeconomic stauts and
      eating habits. The elements levels in the patient group were measured before
      treatment with an atomic absorption spectrophotometer. The selection criteria for
      the patients and controls were the lack of recent blood transfusion history and
      taking any medication with mineral supplement. RESULTS: The acute leukemia group
      composed of 42 patients and there were 40 persons in the control group. There was
      no difference between the age of the two groups (p=0.239). Serum levels of Zn, Mg
      and Mn were significantly lower with acute leukemia than in controls (p<0.001,
      p=0.011, p<0.001, respectively), while Cu, Pb and Cd were significantly elevated
      (p=0.003, p<0.001, p<0.001, respectively). There were no significant differences
      regarding Co and Fe (p=0.323 and p=0.508, respectively) CONCLUSION: In this
      study, we found levels of Zn, Mg and Mn to be lowered and of Cu, Pb and Cd to be
      elevated in patients with leukemia. Further studies are needed to clarify the
      role of these elements in pathogenesis of acute leukemia.

PMID- 22471500
TI  - Diagnostic significance of alpha fetoprotein in carcinomas of liver and biliary
      tract - a comparative study from the western region of Nepal.
AB  - OBJECTIVE: To assess the diagnostic significance of alpha-fetoprotein in
      carcinomas of liver and biliary tract with the overall goal of reducing morbidity
      and mortality in Pokhara valley. MATERIALS AND METHODS: It was a hospital based
      comparative study carried out in the Department of Biochemistry of Manipal
      Teaching Hospital, Pokhara, Nepal between 1st January 2009 and 31st December
      2010. The variables collected were age, gender, serum alpha feto protein.
      Approval for the study was obtained from the institutional research ethical
      committee. Estimation of AFP was performed by ELISA reader for all cases. The
      standard procedure was followed as per manufacturer's instructions for ELISA. All
      these laboratory parameters were analyzed using Human reagent kits and with the
      help of ELISA and semi autoanalyser (Humalyser 3500, Germany). RESULTS: Out of
      1200 patients, there were 348(29%) cases of HCC. Out of that, 285 cases were
      found to be AFP positive with significant elevation. Furthermore, diagnosed cases
      were of cholangiocarcinomas (96, 8%) and secondary carcinomas of liver (216,
      18%). In both of these clinical conditions, there was insignificant elevation of
      AFP. Another commonly diagnosed condition was cirrhosis (480, 40%) and in 90
      cases, AFP values were moderately raised from the upper limit of normal reference
      range. The last diagnosed cases were of either Hepatitis A/E(60, 5%) and did not
      show any rise in levels of AFP. CONCLUSION: Serological markers for
      hepatocellular carcinoma (HCC) are imperative for early identification, as well
      as scrutinizing of tumour aggressiveness, treatment responsiveness, reappearance
      and endurance. It is consequently justifiable to carry out the test for serum AFP
      to detect and differentiate at early stage of liver cell carcinomas.

PMID- 22471501
TI  - Overexpression of triosephosphate isomerase inhibits proliferation of chicken
      embryonal fibroblast cells.
AB  - Triosephosphate isomerase (TPI), a glycolytic enzyme, functions in catalyzing the
      interconversion of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate and
      is generally upregulated in tumours. However, there are data suggesting loss in
      lymphomas. To determine its effects in chicken embryonal fibroblasts (CEF) a
      plasmid was constructed to allow transfection. Upon culture in a suitable medium,
      cells transfected with the TPI demonstrated upregulation and were significantly
      more susceptible to apoptosis compared to controls with decreased proliferation.
      These finding therefore render a novel mechanism by which CEF can be triggered to
      undergo death by upregulation of TPI.

PMID- 22471502
TI  - Cochinchina momordica seed extract induces G2/M arrest and apoptosis in human
      breast cancer MDA-MB-231 cells by modulating the PI3K/Akt pathway.
AB  - Cochinchina momordica seeds are a kind of traditional Chinese herb. In this
      study, anticancer activity and underlying mechanisms were investigated with an
      extract using human breast cancer MDA-MB-231 cells. The survival rate was reduced
      in a concentration- and time-dependent manner as assessed by MTT assay. After
      incubation for 48 h, typical apoptotic morphological changes were observed by
      Hoechst 33258 dye assay. Flow cytometry revealed that the treatment obviously
      induced G2/M arrest and apoptosis in MDA-MB-231 cells. Furthermore, western
      blotting demonstrated downregulation of protein expression of PI3K, Akt, NF-kB,
      Bcl-2, Cdk1 and cyclin B1, whereas Bax and caspase-3 were upregulated. Our
      results suggest that the extract induced cell cycle G2/M arrest and apoptosis in
      MDA-MB-231 cells by decreasing PI3K/Akt pathway. Therefore, we propose that ECMS
      has potential as a breast cancer chemotherapeutic agent.

PMID- 22471503
TI  - Trends in the National Cancer Screening Program for colorectal cancer in the
      Republic of Korea, 2004-2009.
AB  - Since 2004, the National Cancer Screening Program (NCSP) for colorectal cancer
      has provided annual screening by fecal immunochemical test (FIT) for individuals
      aged 50 years or older in the Republic of Korea. This study was conducted to
      investigate trends in the participation rate of the NCSP for colorectal cancer
      overall and according to gender, age and health insurance type. Therefore, we
      analyzed participation, positivity, and follow-up rates according to these
      factors. Overall participation rates for the NCSP for colorectal cancer increased
      from 10.5% in 2004 to 26.2% in 2009. FIT positivity rates decreased from 7.9% in
      2004 to 7.1% in 2009. Follow-up rates among FIT-positive participants decreased
      from 64.5% in 2004 to 39.4% in 2009. Although the participation rate increased
      each year during the study period, it remained low compared with that of other
      countries. The FIT positivity rate decreased, however it was relatively high
      compared with that of other countries. Intervention is essential to raise
      participation rates, maximize adherence to screening recommendations, and to make
      certain that all population subgroups reap the benefits of screening. Also, these
      data suggest that structured and standardized quality improvement activity is
      essential to high quality for FIT in the NCSP for colorectal cancer screening in
      Korea.

PMID- 22471504
TI  - The current status of gastric cancer screening in Korea: report on the National
      Cancer Screening Programme, 2009.
AB  - OBJECTIVE: The objective of this study was to evaluate the results of the
      National Cancer Screening Programme (NCSP) for gastric cancer in 2009 and provide
      the rates of participation in organized gastric cancer screening in Korea.
      METHODS: The data were obtained from the National Cancer Screening Information
      System, and the participation rates in gastric cancer screening were calculated.
      Recall rates, defined as the proportion of abnormal cases among participants,
      were estimated with 95% confidence intervals (CIs). RESULTS: The target
      population of the 2009 NCSP included 6,842,209 Korean men and women aged 40 and
      older. Of those adults, 2,328,715 were screened with upper endoscopy or upper
      gastrointestinal (UGI) series (34.0%). For the first time, the number of adults
      (56.3%) screened with upper endoscopy exceeded the number screened with UGI
      series. Participation rates varied by gender and health insurance type. Overall,
      the recall rates of upper endoscopy and UGI series were 0.3% (95% CI, 0.34 to
      0.36) and 1.6% (95% CI, 1.62 to 1.67), respectively. CONCLUSIONS: According to
      our research, efforts to facilitate participation and to reduce disparities in
      gastric cancer screening among Korean men and women are needed.

PMID- 22471505
TI  - Q fever and spontaneous abortion.
AB  - Q fever, caused by Coxiella burnetii, may result in abortions in infected animals
      and pregnant women. However, the role that Q fever plays in spontaneous abortions
      is still unknown. This study examined the association between Q fever serology
      and abortion in a region where Q fever is endemic. A case-control population
      based study was conducted in General Yague Hospital (Burgos area, Spain) between
      June 2009 and July 2010. A total of 801 samples from 500 pregnant women were
      tested, of whom 273 had a spontaneous abortion and 227 gave birth. IgG and IgM
      antibody titres against Q fever were determined in their two phases (I and II) by
      immunofluorescence assay. Seropositivity (phase I IgG >=1:16 or phase II IgG
      >=1:80) was detected in 88/273 (32.2%) cases and 53/227 (23.3%) controls; p
      <0.01, OR 1.5, 95% CI 1.0-2.3. Seropositivity for both phases of IgG, compatible
      with recent or persistent infection, was detected in 55 (20.1%) vs 22 (9.7%); p
      <0.001, OR 2.3, 95% CI 1.3-3.9. High phase II IgG antibodies compatible with
      active or recent infection (titres >=1:160) were detected in 27 (9.6%) vs 7
      (3.1%); p <0.002, OR 3.4, 95% CI 1.4-8.0, respectively. Q fever was diagnosed in
      14 (5.1%) cases. The risk of abortion associated with serological markers of
      active or recent Q fever in pregnant women was measurable and noticeable in this
      population, and accounted for 12% (95% CI 4-21%).

PMID- 22471506
TI  - Safety and efficacy of ureteroscopic lithotripsy for stone disease in obese
      patients: a systematic review of the literature.
AB  - OBJECTIVE: To look at the role and safety of ureteroscopy for stone management in
      obese patients. METHODS: We searched MEDLINE, PubMed and the Cochrane Library
      from January 1990 to June 2011 for results of ureteroscopy and stone treatment in
      obese patients. Inclusion criteria were all English language articles reporting
      on ureteroscopy in patients with morbid obesity. Data on the outcomes and
      complications was extracted and a meta-analysis of the results conducted.
      RESULTS: Seven studies with 131 patients (136 renal units) were included. All the
      studies included obese patients (mean BMI 42.2) treated with flexible URS for
      urinary calculi. The mode of fragmentation was pulse dye laser, holmium laser,
      and combined modality including electrohydraulic lithotripsy and basket retrieval
      in others. The average stone size was (1.37). The stone free rate was 87.5% after
      completion of treatment with a ranged follow up between 3 months and 3.5 years.
      The mean operative time was 97.1 minutes (30-275). There was an overall 11.4%
      complication rate, however, none of the patients needed further monitoring and
      were treated conservatively. A sub-group analysis of the stones depending on size
      found the URS has a higher stone free rate in stones <2 cm in size (P = 0.0003).
      Furthermore, URS has a higher stone free rate when treating ureteric stones
      compared to renal stones (P = 0.04). CONCLUSION: Retrograde stone treatment using
      ureteroscopy is a safe and efficient modality for treating obese patients with
      urinary tract calculi with an increased efficiency with smaller stones less than
      2 cm in size.

PMID- 22471507
TI  - Superconductivity in potassium-doped few-layer graphene.
AB  - Here we report the successful synthesis of superconducting potassium-doped few
      layer graphene (K-doped FLG) with a transition temperature of 4.5 K, which is 1
      order of magnitude higher than that observed in the bulk potassium graphite
      intercalation compound (GIC) KC(8) (T(c) = 0.39 K). The realization of
      superconductivity in K-doped FLG shows the potential for the development of new
      superconducting electronic devices using two-dimensional (2D) graphene as a basis
      material.

PMID- 22471508
TI  - SseF, a type III effector protein from the mammalian pathogen Salmonella
      enterica, requires resistance-gene-mediated signalling to activate cell death in
      the model plant Nicotiana benthamiana.
AB  - Type III effector proteins (T3Es) of many Gram-negative pathogenic bacteria
      manipulate highly conserved cellular processes, indicating conservation in
      virulence mechanisms during the infection of hosts of divergent evolutionary
      origin. In order to identify conserved effector functions, we used a cross
      kingdom approach in which we expressed selected T3Es from the mammalian pathogen
      Salmonella enterica in leaves of Nicotiana benthamiana and searched for possible
      virulence or avirulence phenotypes. We show that the T3E SseF of S. enterica
      triggers hypersensitive response (HR)-like symptoms, a hallmark of effector
      triggered immunity in plants, either when transiently expressed in leaves of N.
      benthamiana by Agrobacterium tumefaciens infiltration or when delivered by
      Xanthomonas campestris pv vesicatoria (Xcv) through the type III secretion
      system. The ability of SseF to elicit HR-like symptoms was lost upon silencing of
      suppressor of G2 allele of skp1 (SGT1), indicating that the S. enterica T3E is
      probably recognized by an R protein in N. benthamiana. Xcv translocating an
      AvrRpt2-SseF fusion protein was restricted in multiplication within leaves of N.
      benthamiana. Bacterial growth was not impaired but symptom development was rather
      accelerated in a compatible interaction with susceptible pepper (Capsicum annuum)
      plants. We conclude that the S. enterica T3E SseF is probably recognized by the
      plant immune system in N. benthamiana, resulting in effector-triggered immunity.

PMID- 22471509
TI  - Elder abuse in Canada--reports from a national roundtable discussion.
      Introduction.

PMID- 22471510
TI  - Understanding "elder abuse and neglect": a critique of assumptions underpinning
      responses to the mistreatment and neglect of older people.
AB  - This article provides an overview of the ways in which the mistreatment and
      neglect of older people have come to be understood as a social problem, one which
      is underpinned by a variety of substantive and theoretical assumptions. It
      connects the process of conceptualizing elder abuse and neglect to political
      economic and social evolution. The authors draw on a review of the literature,
      government sources, interest group websites, and their own research to provide a
      critical commentary illustrating how these understandings have become manifest in
      legislation, policies, and programs pertaining to "elder abuse and neglect" in
      Canada. Suggestions are provided for changes in direction for policies, programs,
      and research.

PMID- 22471511
TI  - Developing an empirical profile for elder abuse research in Canada.
AB  - The aging population of Canada and the associated caregiving demands highlight
      the need for elder abuse research. The objectives of this article are to provide
      a review of literature while identifying recommendations and directions for
      future research. Significant gaps in the knowledge base are identified that
      preclude the development of effective programming and policies. Future research
      directions include prevalence studies in community and institutional settings;
      studies on correlates, risk, and protective factors; research to clarify
      definitional issues and to develop psychometrically sound measurements;
      qualitative studies; and the need to support elder abuse research through
      capacity building and appropriate resource strategies.

PMID- 22471512
TI  - Intimate partner victimization among adults aged 60 and older: an analysis of the
      1999 and 2004 General Social Survey.
AB  - Accounts in both the scientific literature and popular media have brought about
      increased recognition of the reality of elder abuse. However, relatively little
      work has examined intimate partner victimization with respect to older adults. In
      this study, weighted data from cycles 13 (1999) and 18 (2004) of the General
      Social Survey are pooled to examine how factors uniquely influence the prevalence
      and risk of emotional, financial, and physical abuse among adults aged 60 and
      over. Considerations regarding elder abuse committed by spouses, versus abuse of
      older adults more broadly (by their children and other adults), are also
      discussed.

PMID- 22471513
TI  - Institutional abuse of older adults: what we know, what we need to know.
AB  - Although Canadian policies support "aging in place," there still will be a number
      of older adults who will require institutional care in the future. Most research
      on elder abuse, however, has focused on domestic abuse and has paid less
      attention to institutional abuse. The purpose of this article is to
      comprehensively review current research to identify gaps in knowledge and
      methodological issues in the study of institutional abuse. Overall, 49 studies in
      English and 20 studies in French were reviewed, and 11 key-informant interviews
      were conducted with methodological experts. Methodological challenges are
      addressed in light of the review and interviews.

PMID- 22471514
TI  - Feasibility study for a survey measuring abuse and neglect of older adults.
AB  - This feasibility study was prepared by Statistics Canada, under arrangement with
      the Strategic Policy Research Directorate, Human Resources and Skills Development
      Canada (HRSDC). It investigates issues associated with conducting surveys of
      abuse and neglect of older adults in community and institutional settings in
      Canada. A roadmap is provided for the work ahead, including options for a
      sampling frame, collection approaches, estimated costs, and an activity schedule.

PMID- 22471515
TI  - "Flying by the seat of our pants": current processes to share best practices to
      deal with elder abuse.
AB  - We examined current processes used to identify, communicate, and adopt "best
      practices" in the field of elder abuse using an iterative process involving
      literature and Internet reviews, surveys completed by stakeholders, and key
      informant interviews. Results indicate minimal research evidence exists to
      support current assessment and intervention strategies; there is an immediate
      need for more evaluation and research in this area and for improved knowledge
      exchange and translation. Two strategic directions are recommended: to (a) build
      capacity for research and program evaluation to advance knowledge of effective
      practices, and (b) build capacity for knowledge exchange to enhance
      professionals' efforts.

PMID- 22471516
TI  - A multivariate twin study of hippocampal volume, self-esteem and well-being in
      middle-aged men.
AB  - Self-esteem and well-being are important for successful aging, and some evidence
      suggests that self-esteem and well-being are associated with hippocampal volume,
      cognition and stress responsivity. Whereas most of this evidence is based on
      studies on older adults, we investigated self-esteem, well-being and hippocampal
      volume in 474 male middle-aged twins. Self-esteem was significantly positively
      correlated with hippocampal volume (0.09, P = 0.03 for left hippocampus, 0.10, P
      = 0.04 for right). Correlations for well-being were not significant (Ps > 0.05).
      There were strong phenotypic correlations between self-esteem and well-being
      (0.72, P < 0.001) and between left and right hippocampal volume (0.72, P <
      0.001). In multivariate genetic analyses, a two-factor additive genetic and
      unique environmental (AE) model with well-being and self-esteem on one factor and
      left and right hippocampal volumes on the other factor fits the data better than
      Cholesky, independent pathway or common pathway models. The correlation between
      the two genetic factors was 0.12 (P = 0.03); the correlation between the
      environmental factors was 0.09 (P > 0.05). Our results indicate that largely
      different genetic and environmental factors underlie self-esteem and well-being
      on one hand and hippocampal volume on the other.

PMID- 22471517
TI  - Adults with intellectual disabilities and challenging behaviour: the costs and
      outcomes of in- and out-of-area placements.
AB  - BACKGROUND: People with severe challenging behaviour are vulnerable to exclusion
      from local services and removal to out-of-area placements if locally available
      supported accommodation is insufficient to meet their needs. There are concerns
      about the high costs and potentially poorer outcomes of out-of-area placements
      but relatively little is known about how costs and outcomes compare with
      provision for a similar population placed locally. METHODS: Costs, quality of
      care and a wide range of quality of life outcomes for 38 people with intellectual
      disabilities and challenging behaviour living in-area and 38 similar people
      living out-of-area were compared. The two groups were matched as far as possible
      on risk factors for out-of-area placement. The out-of-area group represented two
      thirds of the total number of people who originated from the territory served by
      the largest specialist health service in Wales and were placed in residential
      settings at least 10 miles beyond its boundaries. RESULTS: There was a mixed
      pattern of quality of care and quality of outcome advantages between the two
      types of setting, although in-area placements had a greater number of advantages
      than out-of-area placements. Unexpectedly, out-of-area placements had lower total
      costs, accommodation costs and daytime activity costs. CONCLUSIONS: No overall
      conclusion could be reached about cost-effectiveness. A number of potential
      reasons for the differences in cost were identified. Although additional
      resources may be needed to provide in-area services for those currently placed
      out-of-area, government policy to provide comprehensively for those who want to
      live locally, irrespective of their needs, appears to be attainable.

PMID- 22471519
TI  - Control of membrane biofouling in MBR for wastewater treatment by quorum
      quenching bacteria encapsulated in microporous membrane.
AB  - Recently, enzymatic quorum quenching has proven its potential as an innovative
      approach for biofouling control in the membrane bioreactor (MBR) for advanced
      wastewater treatment. However, practical issues on the cost and stability of
      enzymes are yet to be solved, which requires more effective quorum quenching
      methods. In this study, a novel quorum quenching strategy, interspecies quorum
      quenching by bacterial cell, was elaborated and proved to be efficient and
      economically feasible biofouling control in MBR. A recombinant Escherichia coli
      which producing N-acyl homoserine lactonase or quorum quenching Rhodococcus sp.
      isolated from a real MBR plant was encapsulated inside the lumen of microporous
      hollow fiber membrane, respectively. The porous membrane containing these
      functional bacteria (i.e., "microbial-vessel") was put into the submerged MBR to
      alleviate biofouling on the surface of filtration membrane. The effect of
      biofouling inhibition by the microbial-vessel was evaluated over 80 days of MBR
      operation. Successful control of biofouling in a laboratory scale MBR suggests
      that the biofouling control through the interspecies quorum quenching could be
      expanded to the plant scale of MBR and various environmental engineering systems
      with economic feasibility.

PMID- 22471518
TI  - Frequency of Chlamydia trachomatis in Ureaplasma-positive healthy women attending
      their first prenatal visit in a community hospital in Sapporo, Japan.
AB  - BACKGROUND: Although Chlamydia trachomatis is the most commonly reported pathogen
      that causes urogenital infection such as urethritis or cervicitis, Ureaplasma
      parvum and Ureaplasma urealyticum, which are commensals in the genital tract,
      have also now been recognized as contributors to urogenital infection. However,
      whether the presence of either U. parvum or U. urealyticum is related to that of
      C. trachomatis in the urogenital tract remains unknown. We therefore attempted to
      estimate by PCR the prevalence of C. trachomatis, U. parvum and U. urealyticum in
      endocervical samples obtained from healthy women attending their first prenatal
      visit in Sapporo, Japan. METHODS: The samples were taken from 303 apparently
      healthy women, and the extracted DNAs (n = 280) were used for PCR detection
      targeting C. trachomatis, U. parvum and U. urealyticum. Statistical analysis of
      the data was performed by Fisher's exact test. RESULTS: PCR detection revealed
      that the prevalence of C. trachomatis, U. parvum and U. urealyticum was 14.3%
      (40/280), 41.7% (117/280) and 8.9% (25/280), respectively. C. trachomatis ompA
      genotype D was most frequently identified. Surprisingly, either C. trachomatis or
      Ureaplasma spp. was detected in almost half of the healthy women. Mixed infection
      of C. trachomatis with either U. parvum or U. urealyticum was also observed in
      9.2% (26/280) of the women. There was a significant association between C.
      trachomatis and either U. parvum (p = 0.023) or Ureaplasma total (p = 0.013), but
      not U. urealyticum (p = 0.275). CONCLUSION: This study demonstrated that the
      presence of Ureaplasma had a significant effect on the presence of C. trachomatis
      in the genital tract of healthy women, suggesting that mixed infection is an
      important factor in bacterial pathogenesis in the genital tract.

PMID- 22471520
TI  - Protein expression changes in ovarian cancer during the transition from benign to
      malignant.
AB  - Epithelial ovarian carcinoma has in general a poor prognosis since the vast
      majority of tumors are genomically unstable and clinically highly aggressive.
      This results in rapid progression of malignancy potential while still
      asymptomatic and thus in late diagnosis. It is therefore of critical importance
      to develop methods to diagnose epithelial ovarian carcinoma at its earliest
      developmental stage, that is, to differentiate between benign tissue and its
      early malignant transformed counterparts. Here we present a shotgun quantitative
      proteomic screen of benign and malignant epithelial ovarian tumors using iTRAQ
      technology with LC-MALDI-TOF/TOF and LC-ESI-QTOF MS/MS. Pathway analysis of the
      shotgun data pointed to the PI3K/Akt signaling pathway as a significant
      discriminatory pathway. Selected candidate proteins from the shotgun screen were
      further confirmed in 51 individual tissue samples of normal, benign, borderline
      or malignant origin using LC-MRM analysis. The MRM profile demonstrated
      significant differences between the four groups separating the normal tissue
      samples from all tumor groups as well as perfectly separating the benign and
      malignant tumors with a ROC-area of 1. This work demonstrates the utility of
      using a shotgun approach to filter out a signature of a few proteins only that
      discriminates between the different sample groups.

PMID- 22471521
TI  - Kinetic basis for the differing response to an oxidative lesion by a replicative
      and a lesion bypass DNA polymerase from Sulfolobus solfataricus.
AB  - 8-Oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), a major oxidative DNA lesion,
      exhibits ambiguous coding potential and can lead to genomic mutations. Tight
      control of 8-oxoG bypass during DNA replication is therefore extremely important
      in hyperthermophiles as the rate of oxidative damage to DNA is significantly
      increased at high temperatures. Here we employed pre-steady state kinetics to
      compare the kinetic responses to an 8-oxoG lesion of the main replicative and
      lesion bypass DNA polymerases of Sulfolobus solfataricus, a hyperthermophilic
      crenarchaeon. Upon encountering 8-oxoG, PolB1, the replicative DNA polymerase,
      was completely stalled by the lesion, as its 3' -> 5' exonuclease activity
      increased significantly and outcompeted its slowed polymerase activity at and
      near the lesion site. In contrast, our results show that Dpo4, the lone Y-family
      DNA polymerase in S. solfataricus, can faithfully and efficiently incorporate
      nucleotides opposite 8-oxoG and extend from an 8-oxoG:C base pair with a
      mechanism similar to that observed for the replication of undamaged DNA.
      Furthermore, we show that the stalling of PolB1 at the lesion site can be
      relieved by Dpo4. Finally, the 3' -> 5' exonuclease activity of PolB1 was the
      highest when 8-oxoG was mispaired with an incorrect nucleotide and could
      therefore correct rare mistakes made by Dpo4 during 8-oxoG bypass. These results
      provide a kinetic basis for a potential polymerase switching mechanism during 8
      oxoG bypass whereby Dpo4 can switch with the stalled PolB1 at the replication
      fork to bypass and extend the damaged DNA and then switch off of the DNA
      substrate to allow continued replication of undamaged DNA by the more faithful
      PolB1.

PMID- 22471522
TI  - Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple
      myeloma by up-regulating manganese superoxide dismutase.
AB  - IL (interleukin)-6, an established growth factor for multiple myeloma cells,
      induces myeloma therapy resistance, but the resistance mechanisms remain unclear.
      The present study determines the role of IL-6 in re-establishing intracellular
      redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased
      myeloma cell resistance to agents that induce oxidative stress, including IR
      (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells
      treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining,
      caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and
      mitochondrial membrane depolarization with increased clonogenic survival. IL-6
      combined with IR or Dex increased early intracellular pro-oxidant levels that
      were causally related to activation of NF-kappaB (nuclear factor kappaB) as
      determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels
      and NF-kappaB activation. In myeloma cells, upon combination with hydrogen
      peroxide treatment, relative to TNF (tumour necrosis factor)-alpha, IL-6 induced
      an early perturbation in reduced glutathione level and increased NF-kappaB
      dependent MnSOD (manganese superoxide dismutase) expression. Furthermore,
      knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to
      radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late
      mitochondrial oxidant production in irradiated myeloma cells. The present study
      provides evidence that increases in MnSOD expression mediate IL-6-induced
      resistance to Dex and radiation in myeloma cells. The results of the present
      study indicate that inhibition of antioxidant pathways could enhance myeloma cell
      responses to radiotherapy and/or chemotherapy.

PMID- 22471524
TI  - Use and cost of psychotropic drugs among recipients with autism in a state
      Medicaid fee-for-service programme.
AB  - BACKGROUND: There has been a significant increase in the prevalence of autism in
      the USA in the past few decades. The purpose of this study was to provide recent
      estimates of psychotropic drug use and costs among individuals with autism
      enrolled in Medicaid programme. METHOD: A cross-sectional analysis of 2007
      Mississippi (MS) Medicaid fee-for-service (FFS) programme administrative-claims
      data was performed. Study sample included recipients (<65 years) who had a
      medical services claim with a diagnosis of autism in 2007. Psychotropic drug
      patterns of use and costs were studied. Factors predicting the use of
      psychotropic drugs were identified using logistic regression analyses. Average
      number and cost of psychotropic drug claims per recipient were reported. Costs
      were reported from the perspective of MS Medicaid. RESULTS: In 2007, there were
      1330 recipients with a diagnosis of autism in MS Medicaid FFS programme. Among
      these recipients, 66.32% had a claim for psychotropic drug during the year.
      Roughly 39% of recipients with autism had a claim for antipsychotics, 31.58% for
      stimulants, 19.55% for antidepressants, 19.40% for other psychotropics and 14.81%
      for anxiolytics/hypnotics/sedatives. Results from regression analyses highlighted
      variation in psychotropic drug use by demographic and co-morbid factors. There
      were a total of 12,618 claims for psychotropic drugs filled by recipients with
      autism in 2007, at an average of 14 (+/-12) claims per recipient. The total cost
      of these claims paid for by MS Medicaid FFS programme was ~$2 million.
      Antipsychotics accounted for more than half (~58%) of the total costs, and had
      the highest average cost per claim ($291 +/- 205). CONCLUSIONS: The results of
      this study indicate a high use of psychotropic drugs among individuals with
      autism enrolled in a state Medicaid programme. There is an urgent need to study
      the risk-benefit profile of these drugs in this growing population. Psychotropic
      drug use was found to vary by demographic and co-morbid factors. Among the
      different classes of psychotropic drugs, antipsychotics were the most commonly
      used and had the highest cost per claim.

PMID- 22471523
TI  - Role of carotenoid beta-cryptoxanthin in bone homeostasis.
AB  - Bone homeostasis is maintained through a balance between osteoblastic bone
      formation and osteoclastic bone resorption. Aging induces bone loss due to
      decreased osteoblastic bone formation and increased osteoclastic bone resorption.
      Osteoporosis with its accompanying decrease in bone mass is widely recognized as
      a major public health problem. Nutritional factors may play a role in the
      prevention of bone loss with aging. Among various carotenoids (carotene and
      xanthophylls including beta (beta)-cryptoxanthin, lutein, lycopene, beta
      carotene, astaxanthin, and rutin), beta-cryptoxanthin, which is abundant in
      Satsuma mandarin orange (Citrus unshiu MARC.), has been found to have a
      stimulatory effect on bone calcification in vitro. beta-cryptoxanthin has
      stimulatory effects on osteoblastic bone formation and inhibitory effects on
      osteoclastic bone resorption in vitro, thereby increasing bone mass. beta
      cryptoxanthin has an effect on the gene expression of various proteins that are
      related osteoblastic bone formation and osteoclastic bone resororption in vitro.
      The intake of beta-cryptoxanthin may have a preventive effect on bone loss in
      animal models for osteoporosis and in healthy human or postmenopausal women.
      Epidemiological studies suggest a potential role of beta-cryptoxanthin as a
      sustainable nutritional approach to improving bone health of human subjects. beta
      Cryptoxanthin may be an osteogenic factor in preventing osteoporosis in human
      subjects.

PMID- 22471525
TI  - Use of traditional environmental knowledge to assess the impact of climate change
      on subsistence fishing in the James Bay Region of Northern Ontario, Canada.
AB  - INTRODUCTION: In Canada, unique food security challenges are being faced by
      Aboriginal people living in remote-northern communities due to the impacts of
      climate change on subsistence harvesting. This study used traditional
      environmental knowledge (TEK) to investigate whether there was a temporal
      relationship between extreme climatic events in the summer of 2005, and fish die
      offs in the Albany River, northern Ontario, Canada. Also, TEK was utilized to
      examine a potential shift in subsistence fish species distribution due to climate
      change. METHODS: To investigate whether there was a temporal relationship between
      the fish die-offs of July 2005 (as identified by TEK) and an extreme climatic
      event, temperature and daily precipitation data for Moosonee weather station were
      utilized. To determine if there was an increasing trend in mean maximal summer
      temperatures with year, temperature data were examined, using regression
      analysis. Present-day fish distributions were determined using unpublished TEK
      data collated from previous studies and purposive, semi-directive interviews with
      elders and experienced bushman. RESULTS: Fish die-offs in 2005 occurred during
      the time period 11-18 July, as reported by participants. Recorded air-temperature
      maxima of the two July 2005 heat waves delineate exactly the time period of fish
      die-offs. Two heat waves occurring during the same summer season and so close
      together has never before been recorded for this region. A highly significant (p
      < 0.0009) positive relationship between mean maximal summer temperatures and year
      was evident. Regionally novel fish species were not apparent, utilizing TEK.
      CONCLUSIONS: Traditional environmental knowledge coupled with climate data
      revealed temporal relationships between extreme climatic events in 2005, and fish
      die-offs in the Albany River. Thus, climate change can directly impact food
      security by decreasing the number of fish through mortality - and indirectly
      through population dynamics - by impacting the yield of fish subsistence harvests
      in the future. By contrast, TEK did not reveal northward expansion of novel fish
      species in the Albany River or fish distributional contraction in the western
      James Bay region.

PMID- 22471528
TI  - Waiting in pain.

PMID- 22471529
TI  - Unrelieved pain: a major health care priority.

PMID- 22471526
TI  - Confirmation of an epilepsy modifier locus on mouse chromosome 11 and candidate
      gene analysis by RNA-Seq.
AB  - Epilepsy is a neurological disorder affecting approximately 1% of the worldwide
      population. Mutations in voltage-gated sodium channels have been identified in
      several monogenic epilepsy syndromes. Over 800 mutations have been identified in
      the voltage-gated sodium channel genes SCN1A and SCN2A in human epilepsies,
      including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet
      syndrome. In GEFS+ families, affected members with the same mutation often
      display variability in clinical severity of the disease. This suggests that
      additional genes modify the effect of the primary mutation, resulting in the
      variable clinical presentation. The Scn2a(Q54)  transgenic mouse model has an
      epilepsy phenotype that varies depending on the genetic strain background.
      Scn2a(Q54)  mice congenic on the C57BL/6J strain exhibit delayed seizure onset
      and improved survival compared to (C57BL/6J * SJL/J)F1.Q54 mice. Two modifier
      loci of Scn2a(Q54)  seizure susceptibility were mapped and designated Moe1
      (modifier of epilepsy) on chromosome (chr) 11 and Moe2 on chr 19. To confirm Moe1
      and refine its position, we generated interval-specific congenic lines carrying
      C57BL/6J-derived chr 11 alleles on the SJL/J strain and refined the map position
      to 89-104 Mb. We then used RNA-Seq for candidate analysis in the modifier region.
      C57BL/6J and SJL/J male and female brain RNAs were sequenced, revealing numerous
      significant transcriptome differences and coding single-nucleotide polymorphisms.
      Additional consideration of gene function and expression suggested several strong
      candidate modifier genes, including two voltage-gated calcium channel subunits,
      Cacna1g and Cacnb1, and the proline and acidic amino acid-rich basic leucine
      zipper transcription factor, Hlf.

PMID- 22471530
TI  - Time for the Pharmaceutical Benefits Advisory Committee to set its own agenda.

PMID- 22471531
TI  - What's the score in pain assessment?

PMID- 22471532
TI  - Opioid prescribing in Australian general practice.

PMID- 22471533
TI  - Racial and ethnic identification and quality of care: an Australian perspective.

PMID- 22471534
TI  - Nicotine replacement therapy: evidence from observational studies versus clinical
      trials.

PMID- 22471536
TI  - No more excuses: fracture liaison services work and are cost-effective.

PMID- 22471537
TI  - Exploring melatonin prescribing among customers of compounding pharmacies in
      Australia.

PMID- 22471538
TI  - Neurocysticercosis in Australia: still free of autochthonous cases?

PMID- 22471539
TI  - Waiting in pain: a systematic investigation into the provision of persistent pain
      services in Australia.
AB  - OBJECTIVES: To document and describe outpatient persistent pain management
      services in Australia. DESIGN, PARTICIPANTS AND SETTING: Systematic survey
      conducted between 1 December 2008 and 31 January 2010 of 57 services providing
      outpatient care to adult clients with persistent pain, plus five specialised
      paediatric services throughout Australia. MAIN OUTCOME MEASURES: Service
      structure, including funding processes; activity, including client numbers,
      access to specialised services (inpatient care, pain relief interventions);
      waiting times; and use of allied-health-professional-based pain management
      programs. RESULTS: Of 68 services identified, 57 participated in the study. The
      median waiting time from referral receipt to initial clinical assessment for a
      publicly funded outpatient adult pain management service was 150 days, compared
      with 38.5 days for a privately funded service (P<0.05). There was substantial
      variability among providers in range of services offered, including provision and
      duration of allied-health pain management programs. The level of service
      provision for children and rural patients is notably lower than that reported for
      urban adult constituents. CONCLUSIONS: Persistent pain management services are
      currently unable to meet service requirements adequately, and waiting times are
      more prolonged for publicly funded than privately funded services. Greater
      service provision is required in rural areas and for children.

PMID- 22471540
TI  - Waiting room ambience and provision of opioid substitution therapy in general
      practice.
AB  - OBJECTIVE: To assess whether patients receiving opioid substitution therapy (OST)
      in general practice cause other patients sufficient distress to change practices-
      a perceived barrier that prevents general practitioners from prescribing OST.
      DESIGN, SETTING AND PARTICIPANTS: A cross-sectional questionnaire-based survey of
      consecutive adult patients in the waiting rooms of a network of research general
      practices in New South Wales during August-December 2009. MAIN OUTCOME MEASURES:
      Prevalence of disturbing waiting room experiences where drug intoxication was
      considered a factor, discomfort about sharing the waiting room with patients
      being treated for drug addiction, and likelihood of changing practices if the
      practice provided specialised care for patients with opiate addiction. RESULTS:
      From 15 practices (eight OST-prescribing), 1138 of 1449 invited patients
      completed questionnaires (response rate, 78.5%). A disturbing experience in any
      waiting room at any time was reported by 18.0% of respondents (203/1130), with
      only 3.1% (35/1128) reporting that drug intoxication was a contributing factor.
      However, 39.3% of respondents (424/1080) would feel uncomfortable sharing the
      waiting room with someone being treated for drug addiction. Respondents were
      largely unaware of the OST-prescribing status of the practice (12.1% of patients
      attending OST-prescribing practices [70/579] correctly reported this). Only 15.9%
      of respondents (165/1037) reported being likely to change practices if theirs
      provided specialised care for opiate-addicted patients. In contrast, 28.7%
      (302/1053) were likely to change practices if consistently kept waiting more than
      30 minutes, and 26.6% (275/1033) would likely do so if consultation fees
      increased by $10. CONCLUSIONS: Despite the frequency of stigmatising attitudes
      towards patients requiring treatment for drug addiction, GPs' concerns that
      prescribing OST in their practices would have a negative impact on other
      patients' waiting room experiences or on retention of patients seem to be
      unfounded.

PMID- 22471541
TI  - Prostate-specific antigen levels in men aged 70 years and over: findings from the
      CHAMP study.
AB  - OBJECTIVE: To describe values of serum prostate-specific antigen (PSA) in older
      men without diagnosed prostate cancer, categorised by age and country of birth,
      and to describe self-reported prostate cancer screening. DESIGN, PARTICIPANTS AND
      SETTING: A cohort study (the Concord Health and Ageing in Men Project) involving
      a representative sample of 1434 eligible community-dwelling men with no diagnosis
      of prostate cancer who were aged 70 years and over and living in a defined
      geographic area in Sydney, with baseline data collected between 28 January 2005
      and 4 June 2007. MAIN OUTCOME MEASURES: Serum PSA levels and self-reported
      prostate cancer screening. RESULTS: 11% of men (155) had a PSA level of >=6.5
      ng/mL, increasing from 7.5% of men aged 70-74 years to 31.4% of men aged>=90
      years. PSA levels varied with ethnicity, with Australian-born men (695) having
      the highest levels (median, 2.3 ng/mL; 5th-95th percentile, 0.4-10.1 ng/mL),
      followed by men born in China (n=42; 2.1 ng/mL; 0.4-12.4 ng/mL), United Kingdom
      and Ireland (n=70; 1.9 ng/mL; 0.3-8.9 ng/mL), Greece (n=59; 1.5 ng/mL; 0.2-6.1
      ng/mL), and Italy (n=293; 1.4 ng/mL; 0.3-7.2 ng/mL). A PSA test in the previous 2
      years was reported by 48% of participants, and a digital rectal examination (DRE)
      in the previous 2 years by 37%. CONCLUSIONS: A significant number of men aged
      over 70 years reported recent prostate cancer tests. The PSA level ranges
      reported in this cohort will help with interpreting serum PSA level findings in
      men aged over 70 years.

PMID- 22471542
TI  - A systematic approach to workplace-based assessment for international medical
      graduates.
AB  - OBJECTIVES: To test whether a summative workplace-based assessment (WBA) is
      feasible and acceptable for international medical graduates (IMGs). DESIGN,
      SETTING AND PARTICIPANTS: A 6-month trial with 27 IMGs from teaching hospitals in
      Newcastle, Australia. IMGs were assessed by 65 trained assessors from different
      disciplines, using blueprinted, preset criteria. MAIN OUTCOME MEASURES: Mini
      clinical evaluation exercises, case-based discussions, in-training assessments
      and multisource feedback. At the end of the trial, assessors and candidates gave
      feedback. RESULTS: All IMGs were successful at the end of the assessment. The
      format was well received and acceptable to the candidates and assessors.
      CONCLUSIONS: WBA is feasible and acceptable to assessors and candidates for
      assessment of IMGs, but it is intensive in use of resources and time.

PMID- 22471543
TI  - Autonomy versus futility? Barriers to good clinical practice in end-of-life care:
      a Queensland case.
AB  - Findings from a Queensland coronial inquest highlight the complex clinical,
      ethical and legal issues that arise in end-of-life care when clinicians and
      family members disagree about a diagnosis of clinical futility. The tension
      between the law and best medical practice is highlighted in this case, as doctors
      are compelled to seek family consent to not commence a futile intervention. Good
      communication between doctors and families, as well as community and professional
      education, is essential to resolve tensions that can arise when there is
      disagreement about treatment at the end of life.

PMID- 22471544
TI  - A defence of the requirement to seek consent to withhold and withdraw futile
      treatments.
AB  - Futility assessments, which are unavoidable in end-of-life settings, need to be
      procedurally fair. This necessitates communication between health professionals
      and substitute decisionmakers regarding the decision to define treatments as
      futile. The common law test for whether treatment should be withheld or withdrawn
      is the best interests test. A futile treatment is not in any patient's best
      interests. While it is rare for the law to disagree with a futility determination
      made by health professionals, if a determination has been made without
      consultation and fails to reflect the patient's best interests, the courts will
      overturn it. The best regulatory regimes provide for a balance between the powers
      of health professionals and substitute decisionmakers to make decisions for
      incompetent patients, and for clear and efficient dispute resolution. The
      Queensland law and its requirement for consent to withhold or withdraw futile
      treatment represents a good model of futility determination, with clear powers
      given to substitute decisionmakers and health professionals. Disputes concerning
      the treatment of incompetent patients automatically trigger the appointment of
      the adult guardian as the decisionmaker, and there are avenues for appeal.

PMID- 22471545
TI  - The requirement for bioscience knowledge in medical education.
AB  - The recent 100-year anniversary of the Flexner review and the release of the
      Australian Medical Education Study have stimulated vigorous debate about the role
      of bioscience knowledge in medical education. Two critical questions define
      debate in this area: does bioscience learning assist in educating medical
      students to become competent doctors, and, if so, what are the most effective
      teaching and learning methods to facilitate this outcome? There is tacit
      acceptance that specific bioscience knowledge is critical for the development of
      clinical expertise; however, there are few empirical data to support this notion.
      Two differing theories have been proposed to describe the role of bioscience
      learning in the development of clinical reasoning skills - the "two-worlds" model
      and the "encapsulation" model. A series of studies provides support for the
      encapsulation model. Some medical programs are now integrating bioscience
      teaching into the clinical years of the course. Evidence of the effectiveness of
      this on outcomes, such as improved clinical reasoning, is inconclusive.

PMID- 22471546
TI  - First-person neuroscience and the understanding of pain.

PMID- 22471547
TI  - Splendid isolation: the winners of our creative writing competition.

PMID- 22471548
TI  - Hands off the breech.

PMID- 22471549
TI  - In my darkness.

PMID- 22471551
TI  - Role of the N-terminus in determining metal-specific responses in the E. coli Ni-
      and Co-responsive metalloregulator, RcnR.
AB  - RcnR (resistance to cobalt and nickel regulator) is a 40-kDa homotetrameric
      protein and metalloregulator that controls the transcription of the Co(II) and
      Ni(II) exporter, RcnAB, by binding to DNA as an apoprotein and releasing DNA in
      response to specifically binding Co(II) and Ni(II) ions. Using X-ray absorption
      spectroscopy (XAS) to examine the structure of metals bound and lacZ reporter
      assays of the transcription of RcnA in response to metal binding, in WT and
      mutant proteins, the roles of coordination number, ligand selection, and residues
      in the N-terminus of the protein were examined as determinants in metal ion
      recognition. The studies show that the cognate metal ions, Co(II) and Ni(II),
      which bind in (N/O)(5)S six-coordinate sites, are distinguished from non-cognate
      metal ions (Cu(I) and Zn(II)), which bind only three protein ligands and one
      anion from the buffer, by coordination number and ligand selection. Using
      mutations of residues near the N-terminus, the N-terminal amine is shown to be a
      ligand of the cognate metal ions that is missing in the complexes with non
      cognate metal ions. The side chain of His3 is also shown to play an important
      role in distinguishing metal ions. The imidazole group is shown to be a ligand in
      the Co(II) RcnR complex, but not in the Zn(II) complex. Further, His3 does not
      appear to bind to Ni(II), providing a structural basis for the differential
      regulation of RcnAB by the two cognate ions. The Zn(II) complexes change
      coordination number in response to the residue in position three. In H3C-RcnR,
      the Zn(II) complex is five-coordinate, and in H3E-RcnR the Zn(II) ion is bound to
      six protein ligands. The metric parameters of this unusual Zn(II) structure
      resemble those of the WT-Ni(II) complex, and the mutant protein is able to
      regulate expression of RcnAB in response to binding the non-cognate ion. The
      results are discussed within a protein allosteric model for gene regulation by
      metalloregulators.

PMID- 22471552
TI  - Bioavailability, toxicity, and bioaccumulation of quantum dot nanoparticles to
      the amphipod Leptocheirus plumulosus.
AB  - Understanding the relative toxicities of different modes of nanoparticle exposure
      as compared with their dissolved metal ions are emerging areas in ecotoxicology.
      Here, we report on bioavailability, toxicity, and bioaccumulation of carboxyl
      functionalized CdSe/ZnS quantum dots (QDs) to the amphipod Leptocheirus
      plumulosus exposed to equivalent Cd concentrations via dissolved Cd, QDs in
      water, or QDs in algal food. Both modes of QD exposure were accumulated to
      greater extent than dissolved Cd. Exposure to QDs via algae resulted in high
      amphipod mortality. Cadmium and Se in amphipods exposed to QDs in water were
      highly correlated and spatially localized within the amphipod. In contrast, when
      exposed to QDs via algae the metals were more disperse and not highly correlated
      suggesting QD dissolution and resultant metal ion toxicity. This study suggests
      QDs are accumulated to a greater extent than the dissolved ion and could lead to
      trophic transfer. QDs ingested with algae are bioavailable and result in
      toxicity, which is not observed in the absence of algae.

PMID- 22471553
TI  - Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the
      prevention of invasive fungal infections among high-risk neutropenic patients in
      Spain.
AB  - BACKGROUND: We evaluated the cost-effectiveness of posaconazole compared with
      standard azole therapy (SAT; fluconazole or itraconazole) for the prevention of
      invasive fungal infections (IFI) and the reduction of overall mortality in high
      risk neutropenic patients with acute myelogenous leukaemia (AML) or
      myelodysplastic syndromes (MDS). The perspective was that of the Spanish National
      Health Service (NHS). METHODS: A decision-analytic model, based on a randomised
      phase III trial, was used to predict IFI avoided, life-years saved (LYS), total
      costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS)
      over patients' lifetime horizon. Data for the analyses included life expectancy,
      procedures, and costs associated with IFI and the drugs (in euros at November
      2009 values) which were obtained from the published literature and opinions of an
      expert committee. A probabilistic sensitivity analysis (PAS) was performed.
      RESULTS: Posaconazole was associated with fewer IFI (0.05 versus 0.11), increased
      LYS (2.52 versus 2.43), and significantly lower costs excluding costs of the
      underlying condition (?6,121 versus ?7,928) per patient relative to SAT. There is
      an 85% probability that posaconazole is a cost-saving strategy compared to SAT
      and a 97% probability that the ICER for posaconazole relative to SAT is below the
      cost per LYS threshold of ?30,000 currently accepted in Spain. CONCLUSIONS:
      Posaconazole is a cost-saving prophylactic strategy (lower costs and greater
      efficacy) compared with fluconazole or itraconazole in high-risk neutropenic
      patients.

PMID- 22471554
TI  - Multimodel pathway enrichment methods for functional evaluation of expression
      regulation.
AB  - Functional analysis of quantitative expression data is becoming common practice
      within the proteomics and transcriptomics fields; however, a gold standard for
      this type of analysis has yet not emerged. To grasp the systemic changes in
      biological systems, efficient and robust methods are needed for data analysis
      following expression regulation experiments. We discuss several conceptual and
      practical challenges potentially hindering the emergence of such methods and
      present a novel method, called FEvER, that utilizes two enrichment models in
      parallel. We also present analysis of three disparate differential expression
      data sets using our method and compare our results to other established methods.
      With many useful features such as pathway hierarchy overview, we believe the
      FEvER method and its software implementation will provide a useful tool for peers
      in the field of proteomics. Furthermore, we show that the method is also
      applicable to other types of expression data.

PMID- 22471555
TI  - Structural and functional interactions between extraradical mycelia of
      ectomycorrhizal Pisolithus isolates.
AB  - Extraradical mycelia from different ectomycorrhizal (ECM) roots coexist and
      interact under the forest floor. We investigated structural connections of
      conspecific mycelia and translocation of carbon and phosphorus between the same
      or different genets. Paired ECM Pinus thunbergii seedlings colonized by the same
      or different Pisolithus isolates were grown side by side in a rhizobox as their
      mycelia contacted each other. (14)CO(2) or (33)P-phosphoric acid was fed to
      leaves or a spot on the mycelium in one of the paired seedlings. Time-course
      distributions of (14)C and (33)P were visualized using a digital autoradiographic
      technique with imaging plates. Hyphal connections were observed between mycelia
      of the same Pisolithus isolate near the contact site, but hyphae did not connect
      between different isolates. (14)C and (33)P were translocated between mycelia of
      the same isolate. In (33)P-fed mycelia, accumulation of (33)P from the feeding
      spot toward the host ECM roots was observed. No (14)C and (33)P translocation
      occurred between mycelia of different isolates. These results provide direct
      evidence that contact and hyphal connection between mycelia of the same ECM
      isolate can cause nutrient translocation. The ecological significance of contact
      between extraradical mycelia is discussed.

PMID- 22471556
TI  - Pathologic ultrasound findings and risk for congenital anomalies in teenage
      pregnancies.
AB  - OBJECTIVE: To detect the number and diagnosis of fetal malformations in teenage
      pregnancies and to evaluate whether low maternal age or epigenetic factors have
      an influence on this issue. MATERIALS AND METHODS: We performed a retrospective
      analysis in a single center for prenatal diagnostics in Northern Germany. We
      searched our electronic databank for all pregnancies with maternal age under 20
      years. Pregnancy outcome and fetal malformations are described. RESULTS: The
      incidence of teenage pregnancies in our study was 638 patients (4.4%). The total
      of fetal malformations in teenage pregnancies was 51(8.3%). Chromosomal
      aberrations were found in 5 cases (0.9%). 9 cases of fetal gastroschisis as one
      of the most frequent malformations were followed up and neonatal outcome was
      uneventful. Furthermore we found 16 cases with different heart defects and 30
      cases with other malformations. Patients' body mass indices showed an increase
      over the years and nicotine consumption was testified in more than 50% of the
      patients. CONCLUSIONS: Teenage pregnancies are at risk for fetal non-chromosomal
      and chromosomal abnormalities. As these might be detected by first-trimester
      screening prenatal care in teenage pregnancies should include at least early
      ultrasound examination. Epigenetic factors may play a key role in certain fetal
      malformations.

PMID- 22471558
TI  - Prospective evaluation of interobserver variability of the hydronephrosis index
      and the renal resistive index as sonographic examination methods for the
      evaluation of acute hydronephrosis.
AB  - OBJECTIVE: To confirm the reliability of assessements of the renal resistive
      index (RRI) and the hydronephrosis index (HI) comprising two sonographic
      techniques providing additional information in patients with acute renal colic.
      PATIENTS AND METHODS: Sonographic measurement of hydronephrosis and assessment of
      common clinical criteria was performed in 22 consecutive patients presenting with
      unilateral stone-related renal colic. RRI and HI were separately recorded by two
      investigators within a prospective study. Interobserver agreement and comparison
      of sonographic with computed tomography (CT) findings were assessed with the
      Cohen's kappa statistic (kappa) for attributive ordinal characteristics and
      Spearman's rank correlation/rho (rho) for attributive metric characteristics.
      RESULTS: There was a significant correlation between HI and the sonographically
      evaluated grade of hydronephrosis, although not between RRI and the grade of
      hydronephrosis. For all procedures (RRI, HI, sonography and CT), significant
      differences between the symptomatic and the asymptomatic kidney were assessed.
      Interobserver agreement was excellent for the grade assessment of hydronephrosis
      by conventional sonography (kappa = 0.82; P < 0.001), good to very good for HI
      (rho = 0.60; P = 0.003) and acceptable to good for RRI (rho = 0.49; P = 0.021).
      CONCLUSIONS: The RRI and HI methods are both easily practicable as stageless
      examination methods in patients presenting with stone-related renal colic, and
      both also reliably distinguish between obstruction and non-obstruction. Exact
      thresholds for both methods must still be defined based on further successive
      studies. Additionally, changes of values under medical expulsive therapy and
      correlation with the functional status of the obstructed kidney remain to be
      examined.

PMID- 22471557
TI  - Energetic and structural basis for activation of the epithelial sodium channel by
      matriptase.
AB  - Limited proteolysis, accomplished by endopeptidases, is a ubiquitous phenomenon
      underlying the regulation and activation of many enzymes, receptors, and other
      proteins synthesized as inactive precursors. Serine proteases make up one of the
      largest and most conserved families of endopeptidases involved in diverse
      cellular activities, including wound healing, blood coagulation, and immune
      responses. Heteromeric alpha,beta,gamma-epithelial sodium channels (ENaC)
      associated with diseases like cystic fibrosis and Liddle's syndrome are
      irreversibly stimulated by membrane-anchored proteases (MAPs) and furin-like
      convertases. Matriptase/channel activating protease-3 (CAP3) is one of the
      several MAPs that potently activate ENaC. Despite identification of protease
      cleavage sites, the basis for the enhanced susceptibility of alpha- and gamma
      ENaC to proteases remains elusive. Here, we elucidate the energetic and
      structural bases for activation of ENaC by CAP3. We find a region near the gamma
      ENaC furin site that has previously not been identified as a critical cleavage
      site for CAP3-mediated stimulation. We also report that CAP3 mediates cleavage of
      ENaC at basic residues downstream of the furin site. Our results indicate that
      surface proteases alone are sufficient to fully activate uncleaved ENaC and
      explain how ENaC in epithelia expressing surface-active proteases can appear
      refractory to soluble proteases. Our results support a model in which proteases
      prime ENaC for activation by cleaving at the furin site, and cleavage at
      downstream sites is accomplished by membrane surface proteases or extracellular
      soluble proteases. On the basis of our results, we propose a dynamics-driven
      "anglerfish" mechanism that explains less stringent sequence requirements for
      substrate recognition and cleavage by matriptase than by furin.

PMID- 22471559
TI  - Effect of gastric acid suppression with pantoprazole on the efficacy of calcium
      carbonate as a phosphate binder in haemodialysis patients.
AB  - AIM:   Metallic phosphate binders require acidity to dissociate to the free
      metallic ion and bind phosphorus. Altered gastric acidity may, therefore,
      influence phosphate-binding efficacy. We evaluated the clinical effect of
      pantoprazole on the efficacy of calcium carbonate phosphate binders in
      haemodialysis patients. METHODS:   The study had two parts: a cross-sectional
      study (n = 67), and an interventional, crossover, double-blind, randomized,
      placebo-controlled trial in 26 patients given pantoprazole 40 mg daily or placebo
      for two consecutive 6-week periods. RESULTS:   The cross-sectional study showed
      no difference between those on and off acid suppressants in phosphate (1.43 +/-
      0.45 vs 1.46 +/- 0.31 mmol/L, P = 0.782) or other parameters except age (72.2 +/-
      9.8 vs 63.8 +/- 14.8 years, P = 0.01). In the interventional study, phosphate was
      higher during pantoprazole than placebo (1.59 +/- 0.3 vs 1.42 +/- 0.3 mmol/L, P =
      0.005). Serum calcium (2.37 +/- 0.2 vs 2.46 +/- 0.2 mmol/L, P = 0.012) and
      ionized calcium (1.17 +/- 0.1 vs 1.22 +/- 0.1 mmol/L, P = 0.013) were lower
      during pantoprazole treatment. CaxPO(4) (3.76 +/- 0.7 vs 3.48 +/- 0.7 mmol(2)
      /L(2) , P = 0.032) and intact parathyroid hormone (31.9 +/- 21.4 vs 23.6 +/- 17.7
      pmol/L, P = 0.004) were higher on pantoprazole. CONCLUSION:   These results
      demonstrate clinical evidence for an adverse effect of gastric acid suppression
      on the effectiveness of calcium carbonate phosphate binders. Given their frequent
      co-prescription, this interaction may be a minor but common reason why some
      patients fail to control hyperphosphataemia. Clinicians should regularly assess
      the need for acid suppressants. Further studies are needed to investigate
      interactions with other phosphate binders.

PMID- 22471560
TI  - Bivalent and co-operative binding of complement factor H to heparan sulfate and
      heparin.
AB  - FH (Factor H) with 20 SCR (short complement regulator) domains is a major serum
      regulator of complement, and genetic defects in this are associated with
      inflammatory diseases. Heparan sulfate is a cell-surface glycosaminoglycan
      composed of sulfated S-domains and unsulfated NA-domains. To elucidate the
      molecular mechanism of binding of FH to glycosaminoglycans, we performed
      ultracentrifugation, X-ray scattering and surface plasmon resonance with FH and
      glycosaminoglycan fragments. Ultracentrifugation showed that FH formed up to 63%
      of well-defined oligomers with purified heparin fragments (equivalent to S
      domains), and indicated a dissociation constant K(d) of approximately 0.5 MUM.
      Unchanged FH structures that are bivalently cross-linked at SCR-7 and SCR-20 with
      heparin explained the sedimentation coefficients of the FH-heparin oligomers. The
      X-ray radius of gyration, R(G), of FH in the presence of heparin fragments 18-36
      monosaccharide units long increased significantly from 10.4 to 11.7 nm, and the
      maximum lengths of FH increased from 35 to 40 nm, confirming that large compact
      oligomers had formed. Surface plasmon resonance of immobilized heparin with full
      length FH gave K(d) values of 1-3 MUM, and similar but weaker K(d) values of 4-20
      MUM for the SCR-6/8 and SCR-16/20 fragments, confirming co-operativity between
      the two binding sites. The use of minimally-sulfated heparan sulfate fragments
      that correspond largely to NA-domains showed much weaker binding, proving the
      importance of S-domains for this interaction. This bivalent and co-operative
      model of FH binding to heparan sulfate provides novel insights on the immune
      function of FH at host cell surfaces.

PMID- 22471561
TI  - Rigid, perdeuterated lanthanoid cryptates: extraordinarily bright near-IR
      luminophores.
AB  - Near-IR emissive lanthanoid cryptates have been developed with the lanthanoids
      Yb, Nd, Er, and Pr by designing a fully deuterated ligand environment that
      greatly suppresses multiphonon nonradiative deactivation pathways through
      avoidance of high-energy oscillators and rigidification of the ligand backbone.
      Strong luminescence is observed in CD(3)CN for all four lanthanoids. Luminescence
      lifetimes in CD(3)CN are among the highest values for molecular complexes in
      solution reported so far (Yb, tau(obs) = 79 MUs; Nd, tau(obs) = 3.3 MUs). For the
      ytterbium cryptate, the highest luminescence lifetime can be obtained using
      CD(3)OD (tau(obs) = 91 MUs) and even in nondeuterated CH(3)CN the lifetime is
      still unusually high (tau(obs) = 53 MUs). X-ray crystallography and (1)H NMR
      analysis of the corresponding nondeuterated lutetium cryptate suggest that the
      inner coordination sphere in solution is completely saturated by the octadentate
      cryptand and one chloride counterion. All lanthanoid cryptates remarkably show
      complete stability during reversed-phase HPLC measurements under strongly acidic
      conditions.

PMID- 22471562
TI  - Monoclonal antibodies targeting the synthetic peptide corresponding to the
      polybasic cleavage site on H5N1 influenza hemagglutinin.
AB  - BACKGROUND: Avian influenza H5N1 virus is highly pathogenic partially because its
      H5 hemagglutinin contains a polybasic cleavage site that can be processed by
      proteases in multiple organs. METHODS: Monoclonal antibodies (mAb) specific to
      the synthetic peptide of hemagglutinin polybasic cleavage site of H5N1 virus were
      raised and tested for their neutralizing potential. RESULTS: Purified mAb showed
      suppression of H5N1 pseudovirus infection on Madin-Darby Canine Kidney (MDCK)
      cells but the efficacy was less than 50%. Since those mAb are specific to the
      intact uncut polybasic cleavage site of hemagglutinin, their efficacy depends on
      the extent of hemagglutinin cleavage on the viral surface. CONCLUSIONS:
      Proteolytic analysis suggests the low efficacy associated with those mAb may be
      due to proteolytic cleavage already present on the majority of hemagglutinin
      prior to the infection of virus.

PMID- 22471563
TI  - The unavailability of opioid medicine and other legal painkillers.

PMID- 22471564
TI  - The barriers separating low- and middle-income countries from legal painkillers.

PMID- 22471565
TI  - The long and winding road to cannabis legalization.

PMID- 22471566
TI  - Additional considerations.

PMID- 22471567
TI  - Practical experience with legalized cannabis.

PMID- 22471568
TI  - Response to commentaries.

PMID- 22471569
TI  - Adolescent estimation of peer substance use: why it matters.

PMID- 22471570
TI  - Overestimation of peer substance use: additional perspectives.

PMID- 22471571
TI  - Misperceptions of peer substance use among youth are real.

PMID- 22471572
TI  - Faithful friends: teen reporters of peer substance use.

PMID- 22471573
TI  - Standing still or moving forward? A response to the commentaries.

PMID- 22471574
TI  - Conversation with Derek Rutherford.

PMID- 22471575
TI  - Dependence and withdrawal: comparison of the benzodiazepines and selective
      serotonin re-uptake inhibitors.

PMID- 22471576
TI  - Withdrawal or dependence: a matter of context.

PMID- 22471577
TI  - Pricing and tax options to reduce alcohol-related harms.

PMID- 22471578
TI  - Minimum unit price comes of age.

PMID- 22471579
TI  - Methadone treatment as palliation or an individualized process of recovery
      management?

PMID- 22471580
TI  - Counselling during substitution treatment: not enough is too much?

PMID- 22471582
TI  - Protein transport across the cell wall of monoderm Gram-positive bacteria.
AB  - In monoderm (single-membrane) Gram-positive bacteria, the majority of secreted
      proteins are first translocated across the cytoplasmic membrane into the inner
      wall zone. For a subset of these proteins, final destination is within the cell
      envelope as either membrane-anchored or cell wall-anchored proteins, whereas
      another subset of proteins is destined to be transported across the cell wall
      into the extracellular milieu. Although the cell wall is a porous structure,
      there is evidence that, for some proteins, transport is a regulated process. This
      review aims at describing what is known about the mechanisms that regulate the
      transport of proteins across the cell wall of monoderm Gram-positive bacteria.

PMID- 22471583
TI  - Clinical utility of noninvasive fetal trisomy (NIFTY) test--early experience.
AB  - OBJECTIVE: To report the initial experience of noninvasive prenatal diagnosis of
      fetal Down syndrome (The NIFTY test) in a clinical setting. METHODS: The NIFTY
      test was offered as a screening test for fetal Down syndrome to pregnant women
      with a singleton pregnancy at 12 weeks of gestation or beyond. A satisfaction
      questionnaire was sent to the first 400 patients. RESULTS: During a 6-month
      period, 567 NIFTY tests were performed. Over 90% of those studied were ethnic
      Chinese, and the mean age of the women studied was 36 years. The test was
      performed at 12-13 weeks of gestation in 49.21%. The median reporting time was 9
      days. The test was positive for trisomy 21 in eight cases, and for trisomy 18 in
      1 case; all were confirmed by fetal karyotyping. There was no false-positive
      result. Of the questionnaires, 182 completed responses were received. Over 95%
      had complete or almost complete resolution of anxiety. Except for one, all were
      satisfied with the NIFTY test, and all indicated that they would recommend the
      test to their friends. CONCLUSION: The NIFTY test was a highly specific test.
      Unnecessary invasive tests and associated fetal losses could be avoided in almost
      all women who have a normal fetus.

PMID- 22471584
TI  - Early induced protein 1 (PrELIP1) and other photosynthetic, stress and epigenetic
      regulation genes are involved in Pinus radiata D. don UV-B radiation response.
AB  - The continuous atmospheric and environmental deterioration is likely to increase,
      among others, the influx of ultraviolet B (UV-B) radiation. The plants have
      photoprotective responses, which are complex mechanisms involving different
      physiological responses, to avoid the damages caused by this radiation that may
      lead to plant death. We have studied the adaptive responses to UV-B in Pinus
      radiata, given the importance of this species in conifer forests and
      reforestation programs. We analyzed the photosynthetic activity, pigments
      content, and gene expression of candidate genes related to photosynthesis, stress
      and gene regulation in needles exposed to UV-B during a 96 h time course. The
      results reveal a clear increase of pigments under UV-B stress while
      photosynthetic activity decreased. The expression levels of the studied genes
      drastically changed after UV-B exposure, were stress related genes were
      upregulated while photosynthesis (RBCA and RBCS) and epigenetic regulation were
      downregulated (MSI1, CSDP2, SHM4). The novel gene PrELIP1, fully sequenced for
      this work, was upregulated and expressed mainly in the palisade parenchyma of
      needles. This gene has conserved domains related to the dissipation of the UV-B
      radiation that give to this protein a key role during photoprotection response of
      the needles in Pinus radiata.

PMID- 22471585
TI  - Mutation of Ser-50 and Cys-66 in Snapin modulates protein structure and
      stability.
AB  - Snapin is a 15 kDa protein present in neuronal and non-neuronal cells that has
      been implicated in the regulation of exocytosis and endocytosis. Protein kinase A
      (PKA) phosphorylates Snapin at Ser-50, modulating its function. Likewise,
      mutation of Cys-66, which mediates protein dimerization, impairs its cellular
      activity. Here, we have investigated the impact of mutating these two positions
      on protein oligomerization, structure, and thermal stability, along with the
      interaction with SNARE proteins. We found that recombinant purified Snapin in
      solution appears mainly as dimers in equilibrium with tetramers. The protein
      exhibits modest secondary structure elements and notable thermal stability.
      Mutation of Cys-66 to Ser abolished subunit dimerization, but not higher-order
      oligomers. This mutant augmented the presence of alpha-helical structure and
      slightly increased the protein thermal stability. Similarly, the S50A mutant,
      mimicking the unphosphorylated protein, also exhibited a higher helical secondary
      structure content than the wild type, along with greater thermal stability. In
      contrast, replacement of Ser-50 with Asp (S50D), emulating the protein
      phosphorylated state, produced a loss of alpha-helical structure, concomitant
      with a decrease in protein thermal stability. In vitro, the wild type and mutants
      weakly interacted with SNAP-25 and the reconstituted SNARE complex, although S50D
      exhibited the strongest binding to the SNARE complex, consistent with the
      observed higher cellular activity of PKA-phosphorylated Snapin. Our observations
      suggest that the stronger binding of S50D to SNAREs might be due to a
      destabilization of tetrameric assemblies of Snapin that favor the interaction of
      protein dimers with the SNARE proteins. Therefore, phosphorylation of Ser-50 has
      an important impact on the protein structure and stability that appears to
      underlie its functional modulation.

PMID- 22471586
TI  - Associations between six classical HLA loci and rheumatoid arthritis: a
      comprehensive analysis.
AB  - Although the HLA region contributes to one-third of the genetic factors affecting
      rheumatoid arthritis (RA), there are few reports on the association of the
      disease with any of the HLA loci other than the DRB1. In this study we examined
      the association between RA and the alleles of the six classical HLA loci
      including DRB1. Six HLA loci (HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) of 1659
      Japanese subjects (622 cases; 488 anti-cyclic citrullinated peptides (CCP)
      antibody (Ab) positive (82.6%); 103 anti-CCP Ab negative (17.4%); 31 not known
      and 1037 controls) were genotyped. Disease types and positivity/negativity for
      CCP autoantibodies were used to stratify the cases. Statistical and genetic
      assessments were performed by Fisher's exact tests, odds ratio, trend tests and
      haplotype estimation. None of the HLA loci were significantly associated with CCP
      sero-negative cases after Bonferroni correction and we therefore limited further
      analyses to using only the anti CCP-positive RA cases and both anti-CCP positive
      and anti-CCP negative controls. Some alleles of the non-DRB1 HLA loci showed
      significant association with RA, which could be explained by linkage
      disequilibrium with DRB1 alleles. However, DPB1*02:01, DPB1*04:01 and DPB1*09:01
      conferred RA risk/protection independently from DRB1. DPB1*02:01 was
      significantly associated with the highly erosive disease type. The odds ratio of
      the four HLA-loci haplotypes with DRB1*04:05 and DQB1*04:01, which were the high
      risk HLA alleles in Japanese, varied from 1.01 to 5.58. C*07:04, and B*15:18
      showed similar P-values and odds ratios to DRB1*04:01, which was located on the
      same haplotype. This haplotype analysis showed that the DRB1 gene as well as five
      other HLA loci is required for a more comprehensive understanding of the genetic
      association between HLA and RA than analyzing DRB1 alone.

PMID- 22471587
TI  - Relationship between serum levels of tumour necrosis factor-related apoptosis
      inducing ligand and the survival of Chinese peritoneal dialysis patients.
AB  - AIM:   Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can
      counteract inflammation and atherosclerosis, both common causes of morbidity in
      peritoneal dialysis (PD) patients. We examined the relation between serum soluble
      TRAIL (sTRAIL) levels and the outcome of Chinese PD patients. METHODS:   We
      studied 116 new PD patients (67 males, age 56.7 +/- 13.4 years). Baseline serum
      sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest).
      All patients were followed for 20.9 +/- 7.0 months. RESULTS:   Patient survival
      was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months (P =
      0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was
      an independent predictor of patient survival after adjusting for confounding
      factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935-0.991, P
      = 0.010). CONCLUSION:   A higher baseline serum sTRAIL level was associated with
      a better survival of PD patients. The detailed mechanism deserves further
      investigation.

PMID- 22471588
TI  - Barriers to hospital delivery in a rural setting in Coast Province, Kenya:
      community attitude and behaviours.
AB  - INTRODUCTION: A minority of births in sub-Saharan African regions are conducted
      with the supervision of skilled birth attendants. With among the highest world
      wide maternal mortality ratios and the majority of the deaths being associated
      with a lack of trained supervision at delivery, changing delivery practices is a
      major priority in this world region. This study identified attitudes to and
      beliefs about the uptake of hospital services for birthing. METHODS: Data were
      gathered using a combination of individual interviews and group discussions.
      Twelve discussion groups were held with participants who included hospital staff
      and general community members (36 males and 54 females). In addition, individual
      interviews were carried out with 26 mothers who chose not to deliver their babies
      in hospital. RESULTS: Qualitative analysis identified a number of barriers to
      seeking skilled attendants at birth including: lack of resources (monetary,
      transport and access), customer care (lack of partnership between mother and
      health professional), and knowledge and beliefs (lack of knowledge about
      pregnancy and maternal health). CONCLUSIONS: The community must be better
      informed about the costs and benefits of hospital deliveries, while medical
      services must be more sensitive to community needs and preferences. These
      findings prompted the initiation of consultation groups on health and maternal
      issues between health service providers and community organisations.

PMID- 22471589
TI  - Depletion of OLFM4 gene inhibits cell growth and increases sensitization to
      hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric
      cancer cells.
AB  - BACKGROUND: Human olfactomedin 4 (OLFM4) gene is a secreted glycoprotein more
      commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be
      frequently up-regulated in many types of human tumors including gastric cancer
      and it was believed to play significant role in the progression of gastric
      cancer. Although the function of OLFM4 has been indicated in many studies, recent
      evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell
      growth and apoptosis. The aim of this study is to examine the role of gastric
      cancer-specific expression of OLFM4 in cell growth and apoptosis resistance.
      METHODS: OLFM4 expression was eliminated by RNA interference in SGC-7901 and
      MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and
      apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The
      apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2) or
      tumor necrosis factor-alpha (TNF alpha) were assessed in the presence or absence
      of caspase inhibitor Z-VAD-fmk. RESULTS: The elimination of OLFM4 protein by RNA
      interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity
      both in vitro and in vivo by induction of cell G1 arrest (all P < 0.01). OLFM4
      knockdown did not trigger obvious cell apoptosis but increased H2O2 or TNF alpha
      induced apoptosis and caspase-3 activity (all P < 0.01). Treatment of Z-VAD-fmk
      attenuated caspase-3 activity and significantly reversed the H(2)O(2) or TNF
      alpha-induced apoptosis in OLFM4 knockdown cells (all P < 0.01). CONCLUSION: Our
      study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of
      the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can
      sensitize gastric cancer cells to H2O2 or TNF alpha treatment by increasing
      caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition
      and anticancer drugs treatment may provide therapeutic potential in gastric
      cancer intervention.

PMID- 22471590
TI  - The RING-type ubiquitin ligases Pex2p, Pex10p and Pex12p form a heteromeric
      complex that displays enhanced activity in an ubiquitin conjugating enzyme
      selective manner.
AB  - The RING finger peroxins Pex2p, Pex10p and Pex12p are central components of the
      peroxisomal matrix protein import machinery. The RING domain enables each of
      these proteins to exhibit ubiquitin-protein ligase activity, which has been
      linked to ubiquitin-dependent regulation of the peroxisomal import receptor
      Pex5p. The RING peroxins are considered to form a heteromeric complex in vivo,
      although the elucidation of the structural assembly, as well as the functional
      interplay of the RING domains, has remained elusive. Using in vitro approaches,
      we show that the RING domains form a heteromeric complex with Pex10p(RING) as a
      central component that directly binds the Pex2p(RING) and Pex12p(RING). The RING
      domains proved to function as heteromeric pairs that display an Pex10p-dependent
      enhanced ligase activity in an ubiquitin conjugating enzyme-selective manner.

PMID- 22471591
TI  - alpha-blockers, antibiotics and anti-inflammatories have a role in the management
      of chronic prostatitis/chronic pelvic pain syndrome.
AB  - Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on
      the subject? and What does the study add? Individual clinical trials evaluating
      antibiotics, anti-inflammatories and alpha-blockers for the treatment of chronic
      prostatitis/chronic pelvic pain syndrome have shown only modest or even no
      benefits for patients compared with placebo, yet we continue to use these agents
      in selected patients with some success in clinical practice. This network meta
      analysis of current evidence from all available randomized placebo-controlled
      trials with similar inclusion criteria and outcome measures shows that these '3
      As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics,
      anti-inflammatories and alpha-blockers) do offer benefits to some patients,
      particularly if we use them strategically in selected individuals. OBJECTIVES: To
      provide an updated network meta-analysis mapping alpha-blockers, antibiotics and
      anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain
      syndrome (CP/CPPS). * To use the results of this meta-analysis to comment on the
      role of the 3-As in clinical practice. PATIENTS AND METHODS: We updated a
      previous review including only randomized controlled studies employing the
      National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one
      of the outcomes to compare treatment effects in CP/CPPS patients. * A
      longitudinal mixed regression model (network meta-analysis) was applied to
      indirectly assess multiple treatment comparisons (i.e. alpha-blockers,
      antibiotics, anti-inflammatory/immune modulation therapies, alpha-blockers plus
      antibiotics, and placebo). RESULTS: Nineteen studies (1669 subjects) were
      eligible for analysis. * alpha-blockers, antibiotics and anti-inflammatory/immune
      modulation therapies were associated with significant improvement in symptoms
      when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI 
      13.2 to -8.3; P < 0.001), -9.7 (95% CI -14.2 to -5.3; P < 0.001) and -1.7 (95% CI
      -3.2 to -0.2; P= 0.032) respectively, while alpha-blockers plus antibiotics
      resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P <
      0.001). * With respect to responder analysis compared with placebo, anti
      inflammatories showed the greatest response rates (risk ratio 1.7, 95% CI 1.4
      2.1; P < 0.001) followed by alpha-blockers (risk ratio 1.4, 95% CI 1.1-1.8; P=
      0.013) and antibiotics (risk ratio 1.2, 95% CI 0.7-1.9; P= 0.527). CONCLUSIONS:
      alpha-blockers, antibiotics and/or anti-inflammatory/immune modulation therapy
      appear to be beneficial for some patients with CP/CPPS. * The magnitude of effect
      and the disconnect between mean CPSI decrease and response rates compared with
      placebo suggest that directed multimodal therapy, rather than mono-therapy, with
      these agents should be considered for optimal management of CP/CPPS.

PMID- 22471592
TI  - Initiation of the synthesis of 'stress' ABA by (+)-[2 H6 ]ABA infiltrated into
      leaves of Commelina communis.
AB  - The 'fettered' fraction of abscisic acid (ABA) that is held within the
      chloroplasts of unwilted bean and Commelina communis leaves is released when the
      leaves wilt and it is this 'free' ABA that is now proposed to cause the stomata
      to close within 2 or 3 min, well before the rise in total ABA can be detected.
      The large increase in 'stress' ABA begins 2-3 h later. The fettered ABA in a
      centrifuged homogenate is released by hyperosmotic solutions of mannitol (0.8 M)
      and NaCl (0.4 M). Dilute solution of halothane (10 mM) and colchicine (1 mM), the
      detergent sodium dodecyl sulphate (1 mM) the herbicide 2,4-d (0.1 mM) and
      dithiothreitol (0.01 mM) also caused ABA to be released. Zeatin (0.01 mM), cumene
      hydroperoxide (0.01 mM) and CaCl(2) (1 mM) had negligible effects. It was
      postulated that the ABA released from the chloroplasts by wilting could be the
      signal that initiates the synthesis of the dioxygenase and other enzymes
      necessary to produce the rise (up to 40-fold) in the amount of stress ABA that is
      seen 2-3 h later. To test this hypothesis, a solution of (+)-[(2) H(6) ]ABA was
      vacuum infiltrated into unwilted Commelina leaves to mimic the rise in ABA caused
      by wilting and gas chromatography/mass spectrometry of the ABA in the extract
      after 3 h showed that concentrations of (+)-[(2) H(6) ]ABA of up to 0.3 uM
      stimulated synthesis of endogenous [(1) H]ABA by 15-fold in the unwilted leaves.
      A 0.5 uM solution blocked the increase in the amount of ABA formed and also
      reduced the amount of ABA formed in response to a 0.8 M mannitol solution.

PMID- 22471593
TI  - Architecture of the spliceosome.
AB  - Precursor-mRNA splicing is catalyzed by an extraordinarily large and highly
      dynamic macromolecular assemblage termed the spliceosome. Detailed biochemical
      and structural study of the spliceosome presents a formidable challenge, but
      there has recently been significant progress made on this front highlighted by
      the crystal structure of a 10-subunit human U1 snRNP. This review provides an
      overview of our current understanding of the architecture of the spliceosome and
      the RNA-protein complexes integral to its function, the U snRNPs.

PMID- 22471594
TI  - Effect of lipopolysaccharide, cytokines, and catecholamines on brain natriuretic
      peptide release from human myocardium.
AB  - BACKGROUND: During sepsis and septic shock, elevated plasma concentrations of
      brain natriuretic peptide (BNP) have been reported but may be related to several
      underlying mechanisms. The aim of the present experimental study was to
      investigate the effect of lipopolysaccharide (LPS), tumor necrosis factor alpha
      (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), dobutamine
      (Dobu), epinephrine (Epi), and norepinephrine (Nor) on BNP synthesis by atrial
      human myocardium in vitro. METHODS: After the approval of local ethics committee,
      right atrial appendages were obtained during cannulation for cardiac surgery and
      pinned in a isolated organ bath containing 15 ml of Tyrode's modified solution.
      Preparations were oxygenated, maintained at 36 +/- 0.5 degrees C and stimulated
      at a frequency of 1 Hz. A 60-min equilibration period was followed by 180-min
      exposure to 1 MUM endothelin 1 (ET-1; n = 9), 20,000 pg/ml TNF-alpha (n = 10),
      1000 pg/ml IL-1beta (n = 10), 5000 pg/ml IL-6 (n = 10), 10,000 pg/ml LPS (n =
      10), 100 MUM Epi (n = 9), 100 MUM Nor (n = 10), and 100 MUM Dobu (n = 8). No
      product was added in Control group (n = 10). Two BNP dosages were performed: the
      first after 60 min of stabilization and the second after 180 min of stimulation.
      Absolute and relative changes in BNP concentration were compared between groups.
      RESULTS: Exposure to ET-1 significantly increased BNP release as compared with
      Control group. Dobu, Epi, Nor, and LPS significantly increased BNP concentration
      but not TNF-alpha, IL-1beta, or IL-6. CONCLUSIONS: In vitro, LPS, Dobu, Epi, and
      Nor induced BNP synthesis by human atrial myocardium.

PMID- 22471595
TI  - An amperometric biosensor for choline determination prepared from choline oxidase
      immobilized in polypyrrole-polyvinylsulfonate film.
AB  - In this paper, a novel amperometric choline biosensor with immobilization of
      choline oxidase on electrochemically polymerized polypyrrole-polyvinylsulphonate
      (PPy-PVS) film has been accomplished via the entrapment technique. The effects of
      pH and temperature were investigated and optimum parameters were found to be 9.0
      and 60  degrees C, respectively. There are two linear parts in the region between
      1.0 * 10 (-7) - 1.0 * 10 (-6)M (R(2) = 0.997) and 1.0 * 10 (-5) - 1.0 * 10 (-3) M
      (R(2) = 0.986). The storage stability and operation stability of the enzyme
      electrode were also studied.

PMID- 22471596
TI  - Investigation of the simultaneous production of superoxide dismutase and catalase
      enzymes from Rhodotorula glutinis under different culture conditions.
AB  - The simultaneous production production of superoxide (SOD) and catalase (CAT)
      from Rhodotorula glutinis was studied. The effects of temperature, initial medium
      pH, and carbon source on the enzyme activities were investigated. Temperature and
      carbon sources were found to have significant effects on the enzyme activities.
      10 degrees C provided the highest specific CAT and SOD activities as 22.6 U/mg
      protein and 170 U/mg protein, respectively. Glycerol was found to be the best
      carbon source for enzyme activities, providing 113 U/mg protein for CAT and 125
      U/mg protein for SOD, which were also the highest activities obtained in the
      present study.

PMID- 22471597
TI  - Garlicin attenuates reperfusion no-reflow in a catheter-based porcine model of
      acute myocardial infarction.
AB  - OBJECTIVE: To evaluate whether garlicin can attenuate reperfusion no-reflow in a
      catheter-based porcine model of acute myocardial infarction (AMI). METHODS:
      Twenty-two swine were used: six in a sham-operation group, and eight each in the
      control and garlicin groups. The distal part of the left anterior descending
      coronary artery (LAD) in the latter two groups was occluded by a dilated balloon
      for 2 hr, then reperfused for 3 hr. Garlicin (1.88mg/kg) was injected just before
      reperfusion until reperfusion for 1 hr in the garlicin group. Hemodynamic data
      were examined before AMI, 2 hr after occlusion, and 3 hr after reperfusion.
      Myocardial contrast echocardiography (MCE) and pathological staining were
      performed to evaluate the myocardial no-reflow area (NRA). Serum proinflammatory
      cytokines and endothelin (ET)-1 were examined by radioimmunoassay. RESULTS: Left
      ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure
      (LVEDP) significantly improved in the garlicin group after reperfusion compared
      with the control group and also 2hr after AMI (p<0.05 for both). MCE and
      pathological staining both showed garlicin attenuated reperfusion NRA after AMI
      (p<0.05, p<0.01). Garlicin not only decreased serum interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha after reperfusion (p<0.05 for both), but also ET-1
      level (p<0.01). CONCLUSION: Garlicin attenuated reperfusion no-reflow in our
      catheter-based porcrine model of AMI, possibly through decreasing serum
      proinflammatory cytokines and ET-1.

PMID- 22471598
TI  - Determination of normal value of glomerular size in Chinese adults by different
      measurement methods.
AB  - AIM:   Identification of glomerulomegaly is a prerequisite for diagnosis of
      obesity-related glomerulopathy, so measurement of glomerular size is of critical
      importance. METHODS:   A total 100 cases pathologically diagnosed as minor
      glomerular abnormalities or thin basement membrane nephropathy with normal body
      mass index and blood glucose level were selected as the normal value measurement
      group of glomerular size. The mean value of diameters of capillary tuft on the
      glomerular maximum profile was determined using the direct method and indirect
      method with the Motic Med 6.0 digital medical image analysis system. Meanwhile,
      80 cases of different glomerular disease with normal body mass index and blood
      glucose level were also collected. Their glomerular diameters were measured and
      compared with those in the normal value measurement group. RESULTS:   The
      measurement results showed that gender and age had no effects on glomerular
      diameter. The normal value ranges of the diameter on glomerular maximum profile
      were as follows. (i) Pole-containing glomerulus (the glomerulus with vascular
      pole or/and urinary pole): direct method, 101.3-184.9 um; indirect method, 100.3
      183.5 um. (ii) Pole-containing glomerulus plus non-pole glomerulus (the
      glomerulus without poles, the maximum profile of which was larger than that in
      the smallest pole-containing glomerulus): direct method, 108.3-185.9 um; indirect
      method, 107.4-185.4 um. The glomerular diameters of the 80 cases with different
      glomerular disease were all within the aforementioned normal value ranges.
      CONCLUSIONS:   Both methods used in the present study are feasible to measure the
      glomerular diameter and the normal value range of glomerular diameter in Chinese
      adults is established.

PMID- 22471599
TI  - Mouse obesity network reconstruction with a variational Bayes algorithm to employ
      aggressive false positive control.
AB  - BACKGROUND: We propose a novel variational Bayes network reconstruction algorithm
      to extract the most relevant disease factors from high-throughput genomic data
      sets. Our algorithm is the only scalable method for regularized network recovery
      that employs Bayesian model averaging and that can internally estimate an
      appropriate level of sparsity to ensure few false positives enter the model
      without the need for cross-validation or a model selection criterion. We use our
      algorithm to characterize the effect of genetic markers and liver gene expression
      traits on mouse obesity related phenotypes, including weight, cholesterol,
      glucose, and free fatty acid levels, in an experiment previously used for
      discovery and validation of network connections: an F2 intercross between the
      C57BL/6 J and C3H/HeJ mouse strains, where apolipoprotein E is null on the
      background. RESULTS: We identified eleven genes, Gch1, Zfp69, Dlgap1, Gna14, Yy1,
      Gabarapl1, Folr2, Fdft1, Cnr2, Slc24a3, and Ccl19, and a quantitative trait locus
      directly connected to weight, glucose, cholesterol, or free fatty acid levels in
      our network. None of these genes were identified by other network analyses of
      this mouse intercross data-set, but all have been previously associated with
      obesity or related pathologies in independent studies. In addition, through both
      simulations and data analysis we demonstrate that our algorithm achieves superior
      performance in terms of power and type I error control than other network
      recovery algorithms that use the lasso and have bounds on type I error control.
      CONCLUSIONS: Our final network contains 118 previously associated and novel genes
      affecting weight, cholesterol, glucose, and free fatty acid levels that are
      excellent obesity risk candidates.

PMID- 22471600
TI  - Presence of the functional CASPASE-12 allele in Indian subpopulations.
AB  - Most humans lack a functional CASP12 gene, with the nonfunctional variant
      (CASP12p1), found in 100% of the Caucasian and east Asian population, and in
      approximately 80% of people of African descent. However, 20% of Africans carry an
      intact allele of CASP12, which produces a full-length pro-enzyme and increases
      the risk of sepsis. We examined CASP12 allele distribution in persons from
      central and southern Asia and found that CASP12 was significantly present in
      members of the Dravidian language group, particularly in persons from the Indian
      state of Tamil Nadu.

PMID- 22471601
TI  - Synchronization of PER1 protein in parabrachial nucleus in a natural model of
      food anticipatory activity.
AB  - Rabbit pups represent a natural model of food anticipatory activity (FAA). FAA is
      the behavioral output of a putative food entrainable oscillator (FEO). It had
      been suggested that the FEO is comprised of a distributed system of clocks that
      work in concert in response to gastrointestinal input by food. Scheduled food
      intake synchronizes several nuclei in the brain, and the hypothalamus has
      received particular attention. On the contrary, brainstem nuclei, despite being
      among the brain structures to first receive food cues, have been scarcely
      studied. Here we analysed by immunohistochemistry possible oscillation of FOS and
      PER1 proteins through a complete 24-h cycle in the dorsal vagal complex (DVC) and
      parabrachial nucleus (PBN) of 7-8-day-old rabbit pups scheduled to nurse during
      the night (02:00 h) or day (10:00 h), and also in fasted subjects to explore the
      possible persistence of oscillations. We found a clear induction of FOS that
      peaks 1.5 h after nursing in all nuclei studied. PER1 was only synchronized in
      the PBN, reaching highest values 12 h after nursing. Only PER1 oscillations
      persisted, with a shift, in fasted subjects. We conclude that the DVC nuclei are
      probably more related to the transmission of food cues to other brain regions,
      but that the PBN participates in the integration of information essential for
      FAA. Our results support previous findings suggesting that the DVC nuclei, but
      not PBN, are not essential for FAA. We suggest that PBN is a key component of the
      proposed distributed system of clocks involved in FAA.

PMID- 22471602
TI  - Preparation of miniantibodies to Azospirillum brasilense Sp245 surface antigens
      and their use for bacterial detection.
AB  - This article reports the first preparation of miniantibodies to Azospirillum
      brasilense Sp245 surface antigens by using a combinatorial phage library of sheep
      antibodies. The prepared phage antibodies were used for the first time for
      lipopolysaccharide and flagellin detection by dot assay, electro-optical analysis
      of cell suspensions, and transmission electron microscopy. Interaction of A.
      brasilense Sp245 with antilipopolysaccharide and antiflagellin phage-displayed
      miniantibodies caused the magnitude of the electro-optical signal to change
      considerably. The electro-optical results were in good agreement with the
      electron microscopic data. This is the first reported possibility of employing
      phage-displayed miniantibodies in bacterial detection aided by electro-optical
      analysis of cell suspensions.

PMID- 22471603
TI  - Flow cytometric lymphocyte subset analysis using material from frozen whole
      blood.
AB  - Multicenter immune monitoring programs commonly rely on storing and shipping
      cryopreserved peripheral blood mononuclear cells (PBMC), isolated from whole
      blood before freezing. However, under many conditions in the field, facilities to
      separate PBMC are absent. Here, we investigate the feasibility of using whole
      blood (WB) frozen at -80 degrees C as a source of viable lymphocytes for use in
      immunological studies. We compare the percentage of CD4 and CD8 T lymphocytes and
      their subsets from frozen WB with results from cryopreserved PBMC in five random
      healthy blood donors (three female, two male). We report that CD4 and CD8 values
      in lymphocytes from WB frozen up to 120 days were very similar to those of PBMC
      frozen up to 10 days. These data suggest that within the limits of parameters
      investigated in this study, contrary to our original assumptions, whole blood
      frozen at -80 degrees C may in fact be an appropriate source of viable
      lymphocytes for T cell enumeration assays in immunological and epidemiological
      studies.

PMID- 22471604
TI  - Significance of antibody detection in the diagnosis of cryptococcal meningitis.
AB  - Cryptococcus neoformans is the causative agent of Cryptococcosis, a chronic and
      life-threatening infection common in AIDS patients. Sonicated proteins of
      cryptococci were reported to contain antigenic properties. In the present study
      antigens are prepared from cryptococcal culture filtrate and by sonication.
      Secretory antigens are prepared by precipitation of culture filtrate using
      saturated ammonium sulfate followed by dialysis. Prepared antigens are tested for
      the presence of antibodies in the CSF samples of cryptococcal meningitis cases by
      ELISA. Comparison is made between India ink staining, latex antigen test, and the
      antibodies to the sonicated and secretory antigens. The results indicate that
      although antigen could be detected in the majority of samples, antibody could
      also be detected to the extent of 80-85%. It is interesting to note that some
      samples that were negative for India ink staining also showed high antibody
      responses. Hence, antibody detection could be a valuable marker in association
      with India ink staining for the early diagnosis of the cryptococcal infection.
      This test may also counter false positivity encountered in latex antigen test.
      Antibody detection assay would be a viable alternative, which has 83% sensitivity
      and 100% specificity. Thus the presently described test aids in immunodiagnosis
      of cryptococcal infection.

PMID- 22471605
TI  - Analysis of CD8+CD28- T-suppressor cells in gastric cancer patients.
AB  - Host anti-tumor immune responses can be attenuated by suppressor T cells of the
      phenotype CD8(+)CD28(-) (T(s) cells). In the present study, we investigated the
      presence of CD8(+)CD28(-) (T(s) cells) in the peripheral blood compartment of
      gastric cancer (GC) patients. Flow cytometry was used to detect the population of
      CD8(+)CD28(-) T(s) cells present in peripheral blood in therapy naive patients
      with gastric cancer (n = 26), postoperative chemotherapy naive gastric cancer
      patients (n = 23), and healthy controls (n = 27). Meanwhile, the clinical data of
      gastric cancer patients were analyzed. A significant difference in the percentage
      of T(s) cells was observed when comparing peripheral blood samples from cancer
      patients to healthy volunteers (27.08 +/- 1.60% versus 10.86 +/- 0.75%). In the
      patient group, the percentage of CD8(+)CD28(-) cells among lymphocytes was higher
      in patients with LN metastasis than those without LN metastasis. The percentage
      of CD8(+)CD28(-) cells was also related to tumor infiltration and size, but not
      with the degree of differentiation of cancer cells. Moreover, the percentage of
      CD8(+)CD28(-) cells was higher in preoperative gastric cancer patients (26.24 +/-
      1.78%) than in those of postoperation patients (15.79 +/- 1.11%). These findings
      may reflect the possibility of tumor-induced immunosuppression, and they should
      be complemented with further studies.

PMID- 22471606
TI  - Detection of hepatitis B virus PreS1 antigen using a time-resolved
      fluoroimmunoassay.
AB  - The hepatitis B virus (HBV) PreS1 antigen is expressed at the distal most region
      of the envelope protein and contains the hepatocyte receptor-binding site. The
      presence of the HBV PreS1 antigen in serum and liver of HBsAg-positive patients
      is a new marker used for diagnosing HBV infection, and is indicative of viral
      replication. Our objective is to establish a method of time-resolved
      fluoroimmunoassay (TRFIA) with higher sensitivity and broader detection range for
      detecting serum HBV PreS1 antigen. Eu(3+) labeling of antibodies was performed
      with respective labeling kits, and Eu(3+) fluorescence intensity was measured
      with an auto DELFIA1235 TRFIA analyzer. The established method was evaluated for
      its performance. Serum specimens (574 in total) from Wuxi People's Hospital were
      analyzed for PreS1 antigen using the TRFIA and ELISA. The precision, specificity,
      and sensitivity of the TRFIA were clearly better than ELISA. The detection limit
      was 0.01 ng/mL. The average recovery rate for PreS1 antigens was 103.3%. There
      was significant correlation between the PreS1 antigen results obtained by TRFIA
      and ELISA in 374 serum samples with HBV >10(3) IU/mL (chi(2) = 25.04, p < 0.01)
      and 183 HbeAg-positive serum samples (chi(2) = 12.07, p < 0.01). Normal reference
      ranges were established at 0-0.32 ng/mL based on the values obtained from 100
      healthy controls. TRFIA is a significantly effective method for clinical
      detection of serum HBV PreS1 antigens.

PMID- 22471607
TI  - Detection of adiponectin and monocyte chemoattractant protein-1 using a
      calixcrown derivatives-coated protein chip.
AB  - We used a ProteoChip coated with a calixcrown derivative protein linker to
      measure adiponectin and monocyte chemoattractant protein-1 (MCP-1) levels and
      compared the results with commercial enzyme-linked immunosorbent assay (ELISA)
      kits. Adiponectin and MCP-1 levels in normal human serum and RAW264 cell
      supernatants, respectively, were measured. The ProteoChip quantification results
      correlated with those from the ELISA kits; however, the ProteoChip required less
      sample volume, exhibited higher sensitivity, and had a wider detection range. The
      ProteoChip was capable of detecting and quantifying small amounts of protein,
      possibly replacing ELISA kits in evaluating the levels of adiponectin and MCP-1.

PMID- 22471608
TI  - Numerical analysis of an immunochromatographic test strip reader in abused drugs
      screening.
AB  - A point-of-care immunoassay strip reader, UniscanTM, was applied to detect
      methamphetamine, opiate, and marijuana in human urine by providing numerical
      apparent drug concentrations. Calibration curves were determined by a nonlinear
      regression. The cutoff was verified using spiked controls. Clinical samples were
      analyzed and compared with enzyme multiplied immunoassay technique (EMIT). The
      discrepant results were confirmed by gas chromatography-mass spectrometry (GC
      MS). The impacts of interference and cross-reactivity were determined for
      numerous compounds. The coefficients of the calibration curves had a high
      correlation coefficient. The sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and total recovery all had high values
      for spiked controls. For the 19 discrepant results of clinical samples, GC-MS
      confirmed that Uniscan and EMIT were correct for 11 and eight samples,
      respectively. For both methamphetamine and opiate, Uniscan had a lower false
      positive rate, a higher true negative rate, and a higher total recovery rate than
      EMIT. For marijuana, Uniscan had a higher true positive rate and a lower false
      negative rate than EMIT. The Uniscan performed excellently when compared to EMIT.
      It is advantageous for Uniscan to interpret the test result based on digital read
      out, rather than subjective visual judgment.

PMID- 22471609
TI  - Study on the expression of co-stimulatory marker CD134 on CD4+ T cells in HIV-1
      infected individuals.
AB  - CD4+CD25+CD134+ T cells play an important role in suppressing T cell responses to
      foreign pathogens, including human immunodeficiency virus (HIV). Thus, we aimed
      to investigate an increase in these populations in HIV-1-infected individuals. In
      this study, we used a panel of monoclonal antibodies staining of
      CD3/CD4/CD25/CD134. Without antigen stimulation, the expression of
      CD4+CD25+CD134+ T cells in 14 HIV-1-infected and 24 healthy individuals were
      4.01% and 3.21%, respectively. However, there was an increase in the expression
      of CD4 + CD25+CD134+ T cells in HIV-1-infected individuals (6.85%) when
      stimulated with gag peptide. The upregulation of CD4+CD25+CD134+ T cells in HIV-1
      infected individuals may result from activation of naturally occurring or by
      disease-associated antigen stimulation.

PMID- 22471610
TI  - New trends in fluorescence immunochromatography.
AB  - During the last decade, immunochromatographic techniques, in particular
      fluorescence labeled immunochromatography, have become more popular for the
      determination of low concentrations of analytes. It offers several potential
      advantages including highly sensitive detection and wide applications in clinical
      chemistry, bioanalysis, and environmental analysis. Currently, fluorescence
      labeled immunochromatography is not the exclusive preserve for a few specialists
      who are well experienced with antigen-antibody analysis, since the recent
      developments in fluorescence labeled immunochromatography have become widespread,
      from simple screening application to quantitative analysis of analytes. In this
      review, we assembled recent advances in the development and applications of
      fluorescence labeled immunochromatography techniques, considering their potential
      benefits in the future.

PMID- 22471611
TI  - Influence of multicomponent apheresis on donors' haematological and coagulation
      parameters, iron storage and platelet function.
AB  - BACKGROUND AND OBJECTIVES: Multicomponent collection (MCC) enables production and
      processing of various blood components during one apheresis session. In this
      prospective crossover study, the effects of donating platelets (PLTs) and packed
      red blood cells (PRBCs) on donor's blood cell count, coagulation, PLT function
      and iron state were analysed. MATERIALS AND METHODS: Forty-eight MCCs were
      performed using two different cell separators (Fenwal Amicus((r)), CaridianBCT
      Trima Accel((r))). Two units of platelet concentrates and one unit of PRBCs were
      collected during each session. Full blood cell count and iron status were
      obtained on day 0 before and after apheresis, day 2, day 14 and day 42. PLT
      function was analysed by aggregometry and rotation thromboelastometry in parallel
      with coagulation tests before and after MCC and at day 2. RESULTS: Multicomponent
      collection was well tolerated without adverse side effects. Blood cell count and
      iron parameters declined and most of them (haemoglobin, haematocrit, transferrin,
      transferrin saturation and ferritin) were significantly below baseline values
      until at least day 42 after donation. Absent iron stores were seen in 31.3% of
      the donors. In contrast, PLTs significantly exceeded pre-donation values after 14
      days and remained significantly increased for 42 days. After 2 days, coagulation
      parameters were only slightly (P > 0.05) altered, whereas PLT function was
      significantly reduced. CONCLUSION: Multicomponent collection is an obviously safe
      procedure; however, the significant long-term impact on the donor's blood count
      and iron store, as well as impaired PLT function, has to be considered in regard
      to donor safety.

PMID- 22471612
TI  - Universal quantification of structurally diverse natural products using an
      evaporative light scattering detector.
AB  - A lack of good methods for absolute quantification of natural products has
      limited the accuracy of high-throughput screening. Many currently used methods
      for quantification are either too slow or not amenable to the structural
      diversity of natural products. Recent developments in low-temperature evaporative
      light scattering detectors (ELSD-LT) have overcome several historical limitations
      of ELSDs, including analyte decomposition and low sensitivity. Primarily, ELSDs
      have been used for relative quantification and detection of compounds that lack a
      UV chromophore. In this study, we employ an ELSD-LT for absolute quantification
      of natural products. Calibration curves were constructed using a weighted least
      squares analysis for a diverse set of natural products and other compounds. An
      average calibration curve was evaluated for the "universal" quantification of
      natural products. Optimization of ELSD-LT hardware and parameters improved
      sensitivity and throughput and established the utility of ELSD-LT for
      quantification of large natural product libraries.

PMID- 22471613
TI  - Correlation between molecular conformation, packing, and dynamics in
      oligofluorenes: a theoretical/experimental study.
AB  - Fluorene-based systems have shown great potential as components in organic
      electronics and optoelectronics (organic photovoltaics, OPVs, organic light
      emitting diodes, OLEDs, and organic transistors, OTFTs). These systems have drawn
      attention primarily because they exhibit strong blue emission associated with
      relatively good thermal stability. It is well-known that the electronic
      properties of polymers are directly related to the molecular conformations and
      chain packing of polymers. Here, we used three oligofluorenes (trimer, pentamer,
      and heptamer) as model systems to theoretically investigate the conformational
      properties of fluorene molecules, starting with the identification of preferred
      conformations. The hybrid exchange-correlation functional, OPBE, and ZINDO/S-CI
      showed that each oligomer exhibits a tendency to adopt a specific chain
      arrangement, which could be distinguished by comparing their UV/vis electronic
      absorption and (13)C NMR spectra. This feature was used to identify the preferred
      conformation of the oligomer chains in chloroform-cast films by comparing
      experimental and theoretical UV/vis and (13)C NMR spectra. Moreover, the oligomer
      chain packing and dynamics in the films were studied by DSC and several solid
      state NMR techniques, which indicated that the phase behavior of the films may be
      influenced by the tendency that each oligomeric chain has to adopt a given
      conformation.

PMID- 22471614
TI  - Laparoscopic partial nephrectomy in obese patients: a systematic review and meta
      analysis.
AB  - What's known on the subject? and What does the study add? The literature yielded
      only four studies on the subject; however, no clear outcome can be taken from
      individual studies. This review adds a meta-analysis of these four studies to
      make the patient cohort larger and to allow for a greater understanding of the
      procedure in this select group of patients. * To compare the safety and efficacy
      of laparoscopic partial nephrectomy (LPN) in obese and non-obese patients. * We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
      (1966 to November 2011), EMBASE (1980 to November 2011), CINAHL,
      Clinicaltrials.gov, Google Scholar, reference lists of articles and abstracts
      from conference proceedings without language restriction for studies comparing
      LPN in obese and non-obese patients. * Four observational cohort studies were
      included for 256 obese patients compared with 403 non-obese patients who
      underwent LPN. * There was no difference in operative duration (mean difference
      [MD] 5.64, 95% confidence interval [CI]-3.80 to 15.09), warm ischaemic time (MD 
      1.04, 95% CI -2.68 to 0.59), estimated blood loss (MD 53.73, 95% CI 0.72-106.74)
      or hospital stay (MD -0.04, 95% CI -0.30 to 0.22). * There was no difference in
      complications in total (odds ratio [OR] 1.02, 95% CI 0.70-1.49), intraoperative
      complications (OR 0.68, 95% CI 0.30-1.53), or postoperative complications (OR
      1.15, 95% CI 0.75-1.77). * The obese group had significantly more Clavien grade
      III complications (OR 3.95, 95% CI 1.36-11.42), despite the low absolute
      incidence, with 4.3% (11/256) in the obese group vs 1.5% (6/403) in the non-obese
      group. * Experienced laparoscopic surgeons can safely and efficiently perform PN
      for obese patients with comparable results to those of non-obese patients. * The
      likelihood of major (Clavien Classification >= III) complications is higher for
      the obese patient.

PMID- 22471615
TI  - Roles of amino acids in the Escherichia coli octaprenyl diphosphate synthase
      active site probed by structure-guided site-directed mutagenesis.
AB  - Octaprenyl diphosphate synthase (OPPS) catalyzes consecutive condensation
      reactions of farnesyl diphosphate (FPP) with five molecules of isopentenyl
      diphosphates (IPP) to generate C(40) octaprenyl diphosphate, which constitutes
      the side chain of ubiquinone or menaquinone. To understand the roles of active
      site amino acids in substrate binding and catalysis, we conducted site-directed
      mutagenesis studies with Escherichia coli OPPS. In conclusion, D85 is the most
      important residue in the first DDXXD motif for both FPP and IPP binding through
      an H-bond network involving R93 and R94, respectively, whereas R94, K45, R48, and
      H77 are responsible for IPP binding by providing H-bonds and ionic interactions.
      K170 and T171 may stabilize the farnesyl carbocation intermediate to facilitate
      the reaction, whereas R93 and K225 may stabilize the catalytic base (MgPP(i)) for
      H(R) proton abstraction after IPP condensation. K225 and K235 in a flexible loop
      may interact with FPP when the enzyme becomes a closed conformation, which is
      therefore crucial for catalysis. Q208 is near the hydrophobic part of IPP and is
      important for IPP binding and catalysis.

PMID- 22471616
TI  - HLA class I polymorphisms in Tunisian patients with otosclerosis.
AB  - BACKGROUND: Otosclerosis is a common form of hearing impairment among Western
      Eurasian adults. The cause of otosclerosis remains unknown. Autoimmune reaction
      against the otic capsule has been suggested as a possible aetiologic factor in
      otosclerosis. AIM: The present study is the first report to evaluate the
      relationship between class I major histocompatibility complex (MHC) genes (HLA-A,
      HLA-B and HLA-Cw) and genetic susceptibility to otosclerosis in Tunisian
      patients. SUBJECTS AND METHODS: Fifty unrelated Tunisian patients exhibiting
      clinical otosclerosis were typed for HLA-A, HLA-B and HLA-Cw antigens and
      compared with 100 ethnically-matched healthy controls. RESULTS: Increased
      frequencies of HLA-A*03 (OR = 4.16, Pc < 0.043), HLA-B*35 (OR = 2.76, Pc < 0.043)
      and HLA-Cw*03 (OR = 4.57, Pc < 0.043) antigens were found in the patients with
      otosclerosis compared with healthy controls. Individuals with HLA-A*30 (OR=0.25,
      Pc < 0.043), HLA-B*51 (OR = 0.11, Pc < 0.043), HLA-Cw*16 (OR = 0.08, Pc < 0.043)
      and Cw*06 (OR=0.32, Pc < 0.043) antigens have a protective effect against
      otosclerosis. CONCLUSIONS: In conclusion, the data suggest that a variation in
      class I HLA antigens could be a genetic factor involved in susceptibility to
      otosclerosis in the Tunisian population.

PMID- 22471617
TI  - Outcome of ICU survivors: a comprehensive review. The role of patient-reported
      outcome studies.
AB  - Problems survivors face after intensive care unit (ICU) discharge begin while
      they are still in the ward, where many of their specific problems may run
      unrecognized, but they assume a heavy weight when they arrive at their homes and
      face several kind of limitations, from being unable to climb stairs because of
      weight loss, asthenia, dyspnea or joint stiffness to anxiety, depression or post
      traumatic stress disorder. Follow-up consultations have given us a better
      understanding of these specific problems, and the information gained has been
      used to improve intensive care itself and promote a quality service for patients
      and relatives. The aim of this article is to provide an overview on adult ICU
      outcome studies and discuss how they have influenced and improved the delivery of
      intensive care. We will explain how we went from real patients to outcome studies
      and what we have learned concerning the consequences of critical illness and
      critical care. Development of outcome studies, what we have learned through them
      and our own experience will be outlined focusing mainly in four topics:
      mortality, physical disability, neuropsychological disability and health-related
      quality of life. Interventions to improve outcome on these main topics will be
      presented, and we will explain how we went from outcome studies to clinical
      interventions, focusing on the most recent proposals of intervention to improve
      outcome.

PMID- 22471619
TI  - Sleepiness that cannot be overcome: narcolepsy and cataplexy.
AB  - Narcolepsy-cataplexy syndrome is characterized by excessive daytime sleepiness,
      cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal
      sleep. It is strongly associated with the genetic marker, human leucocyte antigen
      (HLA) DQB1*06:02. A deficit in the endogenous hypocretin/orexin system due to
      neuronal degeneration in the lateral hypothalamus, induced by an autoimmune
      mediated process, is the primary pathophysiology associated with the human
      disease. The important finding of an association with hypocretin genes in animal
      models of narcolepsy has led to the establishment of cerebrospinal fluid
      hypocretin measurements as a new diagnostic test for human narcolepsy. This is a
      fascinating story of translation of basic science research into clinical practice
      in sleep medicine during the past decade. Recent advances have shed light on the
      associations between respiratory medicine and narcolepsy-cataplexy research. The
      first is that upper airway infections, including H1N1 and/or streptococcal
      infections, may initiate or reactivate an immune response that leads to loss of
      hypocretin-secreting cells and narcolepsy in genetically susceptible individuals.
      The second is that an increased incidence of sleep disordered breathing among
      narcoleptic subjects may relate to the impairment of central control of
      breathing, linked to hypocretin deficiency or carriage of HLADQB1*06:02, in
      animals and human subjects with narcolepsy, respectively, indicating neural
      dysfunction in an area where respiratory and sleep-wake systems are closely
      interrelated.

PMID- 22471618
TI  - Different selective pressures lead to different genomic outcomes as newly-formed
      hybrid yeasts evolve.
AB  - BACKGROUND: Interspecific hybridization occurs in every eukaryotic kingdom. While
      hybrid progeny are frequently at a selective disadvantage, in some instances
      their increased genome size and complexity may result in greater stress
      resistance than their ancestors, which can be adaptively advantageous at the
      edges of their ancestors' ranges. While this phenomenon has been repeatedly
      documented in the field, the response of hybrid populations to long-term
      selection has not often been explored in the lab. To fill this knowledge gap we
      crossed the two most distantly related members of the Saccharomyces sensu stricto
      group, S. cerevisiae and S. uvarum, and established a mixed population of
      homoploid and aneuploid hybrids to study how different types of selection impact
      hybrid genome structure. RESULTS: As temperature was raised incrementally from 31
      degrees C to 46.5 degrees C over 500 generations of continuous culture, selection
      favored loss of the S. uvarum genome, although the kinetics of genome loss
      differed among independent replicates. Temperature-selected isolates exhibited
      greater inherent and induced thermal tolerance than parental species and founding
      hybrids, and also exhibited ethanol resistance. In contrast, as exogenous ethanol
      was increased from 0% to 14% over 500 generations of continuous culture,
      selection favored euploid S. cerevisiae x S. uvarum hybrids. Ethanol-selected
      isolates were more ethanol tolerant than S. uvarum and one of the founding
      hybrids, but did not exhibit resistance to temperature stress. Relative to
      parental and founding hybrids, temperature-selected strains showed heritable
      differences in cell wall structure in the forms of increased resistance to
      zymolyase digestion and Micafungin, which targets cell wall biosynthesis.
      CONCLUSIONS: This is the first study to show experimentally that the genomic fate
      of newly-formed interspecific hybrids depends on the type of selection they
      encounter during the course of evolution, underscoring the importance of the
      ecological theatre in determining the outcome of the evolutionary play.

PMID- 22471620
TI  - Undecaprenyl diphosphate synthase, a cis-prenyltransferase synthesizing lipid
      carrier for bacterial cell wall biosynthesis.
AB  - A group of prenyltransferases produce linear lipids by catalyzing consecutive
      condensation reactions of farnesyl diphosphate (FPP) with specific numbers of
      isopentenyl diphosphate (IPP), a common building block of isoprenoid compounds.
      Depending on the stereochemistry of the double bonds formed during IPP
      condensation, these prenyltransferases are categorized as cis- and trans-types.
      Undecaprenyl diphosphate synthase (UPPS) that catalyzes chain elongation of FPP
      by consecutive condensation reactions with eight IPP, to form C55 lipid carrier
      for bacterial cell wall biosynthesis, serves as a model for understanding cis
      prenyltransferases. In this review, the current knowledge in UPPS kinetics,
      mechanisms, structures, and inhibitors is summarized.

PMID- 22471622
TI  - Serum gamma-glutamyl transferase level is an independent predictor of incident
      hypertension in Korean adults.
AB  - The aim of our study was to assess the relationship between serum gamma-glutamyl
      transferase (GGT) level within the normal range and incident hypertension
      according to drinking and obesity status in nonhypertensive individuals. We
      followed up 4783 normotensive adults (mean age = 44 years) who had serum GGT
      levels within the normal range at baseline for 3 years. Subjects were divided
      into four GGT quartile groups according to their serum GGT level at baseline. The
      overall incidence of hypertension was 8.1%, and the incidence increased with
      increasing GGT quartile (3.8%, 6.9%, 9.0%, and 12.4% in the lowest, second,
      third, and highest GGT quartiles, respectively; P < .001). In the logistic
      regression analysis adjusted for age, sex, body mass index, lifestyle factors,
      glucose, uric acid, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, triglyceride, high-sensitivity C-reactive protein, and baseline
      systolic blood pressure, the odds ratio (ORs) for incident hypertension increased
      with increasing GGT quartile (P for trend = .030). In the above model, the
      highest quartile group showed increased ORs compared with those in the lowest
      quartile group (ORs [95% confidence interval], 2.638 [1.259-5.528]). Subgroup
      analyses revealed a significant association between GGT quartile and the
      incidence of hypertension in the drinker and non-overweight groups. Our results
      indicate that elevated serum GGT levels within the normal range are associated
      with a higher risk of incident hypertension in Korean adults, particularly, in
      drinkers and non-overweight individuals, suggesting possible different
      pathophysiologic mechanisms in the incidence of alcohol- and obesity-related
      hypertension.

PMID- 22471624
TI  - Characterization of sulfurous acid, sulfite, and bisulfite aerosol systems.
AB  - Acidic tropospheric aerosols contain inorganic species such as sulfurous acid
      (H(2)SO(3)). As the main alkaline species, ammonia (NH(3)) plays an important
      role in the heterogeneous neutralization of these acidic aerosols. An aerosol
      flow-tube apparatus was used to obtain simultaneous optical and size distribution
      measurements using FTIR and SMPS measurements, respectively, as a function of
      relative humidity and aerosol chemical composition. A novel chemiluminescence
      apparatus was also used to measure ammonium ion concentration [NH(4)(+)]. The
      interactions between ammonia and hydrated sulfur dioxide (SO(2).H(2)O) were
      studied at different humidities and concentrations. SO(2).H(2)O is an important
      species as it represents the first intermediate in the overall atmospheric
      oxidation process of sulfur dioxide to sulfuric acid (H(2)SO(4)). This complex
      was produced within gaseous, aqueous, and aerosol SO(2) systems. The addition of
      ammonia gave mainly hydrogen sulfite (SHO(3)(-)) tautomers and disulfite ions
      (S(2)O(5)(2-)). These species were prevalent at high humidities enhancing the
      aqueous nature of sulfur(IV) species. Their weak acidity is evident due to the
      low [NH(4)(+)] produced. Size distributions obtained correlated well with the
      various stages of particulate compositional development.

PMID- 22471623
TI  - The powerful impact of double-layered posterior rhabdosphincter reconstruction on
      early recovery of urinary continence after robot-assisted radical prostatectomy.
AB  - BACKGROUND AND PURPOSE: The usefulness of posterior rhabdosphincter
      reconstruction (PR) during robot-assisted radical prostatectomy (RARP) has still
      been controversial. We investigated the association of several factors, including
      the Rocco original double-layered PR, with early recovery of urinary continence
      after RARP. PATIENTS AND METHODS: Between August 2006 and April 2011, a single
      surgeon at Tokyo Medical University Hospital performed 206 RARPs. Of these 206
      patients, 199 eligible patients were enrolled in this study. We retrospectively
      analyzed the correlation of several perioperative factors, including surgical
      techniques, with early recovery of urinary continence 1 month after catheter
      removal. Continence was defined as no use or the use of only one safety pad.
      RESULTS: Univariate analysis showed that surgeon experience, lateral approach of
      bladder neck preservation, bladder neck reconstruction, anterior reconstruction,
      and the Rocco double-layered PR were significantly associated with early recovery
      of urinary continence 1 month after catheter removal. Preoperative prostate
      specific antigen level, body mass index, and attempted nerve-sparing (NS)
      procedures, however, were not significantly associated with early recovery of
      urinary continence. Multivariate logistic regression analysis showed that the
      Rocco PR and attempted NS were the only independent predictive factors of urinary
      continence recovery 1 month after catheter removal (odds ratio [OR], 15.01; 95%
      confidence interval [CI], 3.413-66.67; P=0.0003 and OR, 2.248; 95% CI, 1.048
      4.975; P=0.0402, respectively). When we applied NS as well as the Rocco PR, the
      recovery rates of continence at 1 month after catheter removal was 85.3%.
      CONCLUSIONS: The Rocco double-layered PR and attempted NS and not surgeon
      experience were the significant independent predictive factors of early recovery
      of urinary continence after RARP. NS procedures positively influenced early
      recovery of urinary continence only when they were applied with the PR technique.

PMID- 22471626
TI  - Plasmon-induced transparency in asymmetric T-shape single slit.
AB  - By utilizing a dielectric-film-coated asymmetric T-shape single slit, comprising
      two grooves of slightly detuned widths immediately contacting with a single
      nanoslit, the plasmon-induced transparency was experimentally demonstrated.
      Because of the symmetry breaking in the unit-cell structure, the scattered lights
      from the two grooves with slightly detuned widths interfere destructively,
      leading to the plasmon-induced transparency. As a result, a response spectrum
      with nearly the same interference contrast but a much narrower bandwidth emerges
      in the unit-cell structure with the footprint of only about 0.9 MUm(2), compared
      with that in the symmetric T-shape single slit. These pronounced features in the
      structure, such as the increased quality factor, ultracompact size, easy
      fabrication, and experimental observation, have significant applications in
      ultracompact plasmonic devices.

PMID- 22471627
TI  - Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting
      the activation of the transforming growth factor-beta signaling pathway.
AB  - BACKGROUND: Huangqi decoction was first described in Prescriptions of the Bureau
      of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an
      effective recipe that is usually used to treat consumptive disease, anorexia, and
      chronic liver diseases. Transforming growth factor beta 1 (TGFbeta1) plays a key
      role in the progression of liver fibrosis, and Huangqi decoction and its
      ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by
      ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic
      fibrotic lesions is not yet clear. The purpose of the present study is to
      elucidate the roles of TGFbeta1 activation, Smad-signaling pathway, and
      extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary
      fibrosis progression and the antifibrotic mechanism of IHQD. METHODS: A liver
      fibrosis model was induced by ligation of the common bile duct (BDL) in rats.
      Sham-operation was performed in control rats. The BDL rats were randomly divided
      into two groups: the BDL group and the IHQD group. IHQD was administrated
      intragastrically for 4 weeks. At the end of the fifth week after BDL, animals
      were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD
      on the TGFbeta1 signaling pathway was evaluated by western blotting and laser
      confocal microscopy. RESULTS: Decreased content of hepatic hydroxyproline and
      improved liver function and histopathology were observed in IHQD rats.
      Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury
      released TGFbeta1, and activated TGFbeta1 receptors can accelerate liver
      fibrosis. IHQD markedly inhibited the protein expression of TGFbeta1, TGFbeta1
      receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression.
      CONCLUSION: IHQD exert significant therapeutic effects on BDL-induced fibrosis in
      rats through inhibition of the activation of TGFbeta1-Smad3 and TGFbeta1-ERK1/2
      signaling pathways.

PMID- 22471628
TI  - High prevalence of aquagenic wrinkling of the palms in patients with cystic
      fibrosis and association with measurable increases in transepidermal water loss.
AB  - Aquagenic wrinkling of the palms (AWP) is a cutaneous phenomenon marked by the
      transient formation of edematous, translucent papules and plaques on the palms
      and fingertips within minutes of water exposure. AWP is anecdotally reported in
      patients with cystic fibrosis (CF) and several studies have recently confirmed
      this association. The primary aim of this study was to determine the prevalence
      of aquagenic wrinkling of the palms in subjects with cystic fibrosis (CF)
      compared to controls, and secondarily to evaluate for genotype-phenotype
      correlations among CF subjects found to have AWP. Fifty-one children with CF and
      25 control children who were being treated for asthma underwent a 5-minute hand
      immersion in lukewarm water. The test for AWP was positive if subjects
      demonstrated >30% wrinkling over the palm. Secondary analyses explored
      associations with genotype, pancreatic and pulmonary function, body mass index
      (BMI), and sweat chloride levels. Palmar transepidermal water loss (TEWL) was
      also measured for all subjects with and without AWP. Forty-three of the subjects
      (84%) with CF demonstrated aquagenic wrinkling, in contrast to none (0%) of the
      controls. These results remained statistically significant when stratified for by
      age and race. TEWL was significantly higher in CF subjects with AWP compared to
      CF subjects without AWP and controls. No genotype-phenotype correlations were
      detected in patients with AWP, nor were there associations of AWP with other
      phenotypic features of CF, although these analyses were likely underpowered.
      Aquagenic wrinkling of the palms is prevalent in children with CF and is
      associated with increased TEWL.

PMID- 22471630
TI  - Reversibly stretchable transparent conductive coatings of spray-deposited silver
      nanowires.
AB  - Here, we report the creation of highly adhesive transparent and stretchable
      coatings via spray-deposition of solution-based silver nanowires (AgNWs). The
      AgNW dispersion was spray-deposited on a polydopamine-modified stretchable
      elastomeric substrate to prepare thin, stretchable, transparent, highly
      conductive films. The polydopamine layer on the elastomeric substrate created a
      highly hydrophilic surface, which facilitated the subsequent spraying of the AgNW
      solution. Additionally, the spray-deposited AgNWs demonstrated excellent adhesion
      to the substrate, which allowed the fabrication of stretchable electrodes with
      high conductivity. The AgNW-coated elastomeric substrate exhibited ~80%
      transmittance with an average sheet resistance of ~35 Omega/?, making it suitable
      for transparent electrode applications. The conductivity of the transparent
      electrode was maintained up to ~20% mechanical elongation, which demonstrated the
      stretchable characteristics of the AgNW-coated elastomeric substrate.

PMID- 22471629
TI  - What do spring migrants reveal about sex and host selection in the melon aphid?
AB  - BACKGROUND: Host plants exert considerable selective pressure on aphids because
      the plants constitute their feeding, mating and oviposition sites. Therefore,
      host specialisation in aphids evolves through selection of the behavioural and
      chemical mechanisms of host-plant location and recognition, and through metabolic
      adaptation to the phloem content of the host plant. How these adaptive traits
      evolve in an aphid species depends on the complexity of the annual life cycle of
      that species. The purpose of this field study was to determine how winged spring
      migrant populations contribute to the evolution and maintenance of host
      specialisation in Aphis gossypii through host-plant choice and acceptance. We
      also assessed whether host-specialised genotypes corresponded exclusively to
      anholocyclic lineages regardless of the environmental conditions. RESULTS: The
      spring populations of cotton-melon aphids visiting newly planted melon crops
      exhibited an unexpectedly high level of genetic diversity that contrasted with
      the very low diversity characterising the host-specialised populations of this
      aphid species. This study illustrated in natura host-plant-selection pressure by
      showing the great differences in genetic diversity between the spring-migrant
      populations (alate aphids) and the melon-infesting populations (the apterous
      offspring of the alate aphids). Moreover, an analysis of the genetic composition
      of these alate and apterous populations in four geographic regions suggested
      differences in life-history strategies, such as host choice and reproductive
      mode, and questioned the common assertion that A. gossypii is an anholocyclic
      species throughout its distribution area, including Europe. CONCLUSIONS: Our
      results clearly demonstrate that the melon plant acts as a selective filter
      against the reproduction of non-specialised individuals. We showed that olfactory
      cues are unlikely to be decisive in natura for host recognition by spring-migrant
      aphid populations that are not specialised on Cucurbitaceae. The agroecosystem
      structure and history of the four studied regions may have partially shaped the
      genetic structure of the spring-migrant populations of A. gossypii. Cucurbitaceae
      specialised genotypes corresponded exclusively to anholocyclic lineages,
      regardless of the environmental conditions. However, some genotypes that were
      genetically close to the host-specialised genotypes and some genotypes that
      probably originated from wild plants had never been previously sampled; both were
      holocylic.

PMID- 22471631
TI  - Molecular structure of thiourea.
AB  - The molecular structure of thiourea has been investigated under C(s), C(2), and
      C(2v) symmetry constraints. At the coupled-cluster level in conjunction with a
      triple-zeta basis set, only the C(2) conformer has been found to be a real
      minimum on the potential energy surface. Its equilibrium structure has therefore
      been accurately evaluated using both theoretical and experimental data. With
      respect to the former, high-level quantum-chemical calculations at the coupled
      cluster level in conjunction with correlation-consistent basis sets ranging in
      size from triple- to quintuple-zeta have been carried out. Extrapolation to the
      complete basis-set limit as well as core-correlation effects and inclusion of
      full treatment of triple excitations in the cluster operator have been
      considered. On the basis of the vibrational ground-state rotational constants
      available for five isotopic species and the corresponding computed vibrational
      corrections, the semiexperimental equilibrium geometry of thiourea has also been
      determined for the first time.

PMID- 22471632
TI  - Female exhibitionism: identification, competition and camaraderie.
AB  - The ancient figure of Baubo plays a pivotal role in the Greek myth of Demeter and
      Persephone with an exhibitionistic act that brings Demeter out of her depression.
      The Baubo episode raises questions about the meaning of female exhibitionism,
      suggesting divergences from earlier psychoanalytic conceptualizations as either a
      perversion or a compensation for the lack of a penis. In line with contemporary
      thinking about primary femininity, such as that of Balsam or Elise, the authors
      propose a more inclusive understanding of female exhibitionism, which would
      encompass pleasure in the female body and its sexual and reproductive functions.
      They argue that female exhibitionism can reflect triangular or "oedipal"
      scenarios and the need to attract the male, identification with the mother,
      competition or camaraderie with other women, a sense of power in the female body
      and its capacities, as well as homoerotic impulses. The authors posit a dual
      early desire and identification with the mother that underlie and characterize
      female sexual development. The authors present clinical data from adolescent and
      adult cases of female exhibitionism which illustrate these Baubo-like aspects and
      discuss the technical issues that are involved in such cases.

PMID- 22471633
TI  - "Without being in psychoanalysis I would never have dared to become pregnant":
      psychoanalytical observations in a multidisciplinary study concerning a woman
      undergoing prenatal diagnostics.
AB  - As is well known, Freud described the clinical practice of psychoanalysis as the
      'loam' of his cultural-theoretical work, an assessment which is shared by many
      psychoanalysts up to the present, including the authors of this paper. The
      complex interplay between unconscious phantasies on the one hand, and the real
      experiences arising from the new possibilities opened up by prenatal diagnostics
      on the other, is described with reference to a report of an intensive, long
      psychoanalysis with an analysand from a family burdened with a genetically
      transmitted illness (haemophilia). The holding and containing function of the
      analyst enabled this analysand, despite traumatic experiences with the
      miscarriage of a healthy child triggered by a prenatal diagnosis and the later
      abortion of a haemophiliac baby, nevertheless to have the courage to go through
      another pregnancy and give birth to a healthy girl. The intensive clinical
      investigation of the unconscious phantasies, conflicts and traumas around the
      prenatal diagnostics proved to be not only therapeutically fruitful for the
      analysand, Ms F. It also facilitated insights into those individual chances and
      risks which appear to be an integral part of the opportunities presented by
      todays prenatal diagnostics and, through them, it lead to a cultural-critical
      look at the ambivalence of medical-technical progress. These insights, which are
      only attainable through psychoanalysis, can represent a distinctive contribution
      of psychoanalysis to a multi-disciplinary dialogue with medical practitioners,
      geneticists, ethicists and health policy-makers. By referring to a large EU study
      on 'Ethical Dilemmas due to Prenatal and Genetic Diagnostics', this paper gives a
      practical example of such a discussion. Ms F. was psychoanalytically interviewed
      as part of this study, 16 years after the conclusion of her analysis. The summary
      of these interviews, which is set against the account of the treatment, offers an
      impressive insight not only into the long-term effects of a psychoanalysis under
      very particular personal circumstances, but also into the lasting consequences of
      decisions made in the context of prenatal diagnostics. Finally, the results of
      the individual case study are brought together with the clinical outcomes of the
      EU study, and some considerations are formulated concerning the protective and
      risk factors facing women during and after prenatal diagnostics. The paper is an
      appeal to psychoanalysts, with their specific competence in dealing with
      unconscious phantasies and conflicts and their high level of professionalism in
      dealing with traumatised patients, to get involved in fresh dialogue with
      prenatal diagnosticians and their patients.

PMID- 22471634
TI  - Some reflections on the unique time of Nachtraglichkeit in theory and clinical
      practice.
AB  - Of the various forms that the matter of time assumes in analysis,
      Nachtraglichkeit represents Freud's first intuition on the subject. The focus of
      this article is directed toward the specific temporal dimension that the concept
      of Nachtraglichkeit expresses, and how that dimension, which overturns linear
      time, is expressed in clinical work. The concept of Nachtraglichkeit is
      approached from a theoretical point of view, tracing back the role and
      development that this notion has had in psychoanalytic Freudian and post-Freudian
      thinking. The goal of this article is to demonstrate how Nachtraglichkeit
      represents the unique temporal movement of the analytic session and the
      characteristic positioning of the mind of the analyst at work. Three clinical
      examples are presented. The analytic scene is formulated as occurring in two
      times, and through the working through that takes place, patients can recover the
      enigmatic 'remainder', which is consequently traumatic and which has compulsively
      accompanied them through the various times of their existence. Nachtraglichkeit,
      as a non-linear temporality, introduces a unique dimension into the clinical work
      that influences listening to and interpretation of the material. The recognition
      of that (trauma, infantile sexuality, non-linear temporality) has consequences
      for the analyst's way of working in session and on the interpretation of clinical
      material, as I will try to show through my theoretical exposition and clinical
      examples.

PMID- 22471635
TI  - An event in medical life, or the advent of a belief?
AB  - Freud's ambivalent relations with medicine are well known. Based on his
      relatively unknown text, A religious experience, published in 1928, the authors
      present an analysis of the internal reasons for this conflict. Responding to a
      letter from an American doctor, who tells him about his reactions to an autopsy
      and the influence it had on his religious faith, Freud suggests an analysis that
      leads him to make a surprising slip. This slip reveals the conflicts inherent in
      the practice of autopsy, considered as a peculiar event in medical training that
      puts a strain on the future medical practitioner's subjectivity. Based on the
      analysis of unconscious impulses and fantasmatic activity, the authors
      demonstrate that Freud's theory is still surprisingly relevant today in the light
      of testimonies from contemporary doctors confronted with autopsy during their
      training or daily practice.

PMID- 22471636
TI  - Whose memories are they and where do they go? Problems surrounding
      internalization in children on the autistic spectrum.
AB  - Recent work in neuroscience has highlighted the contrast between 'procedural'
      memory for bodily experiences and skills, which is unconscious though
      unrepressed, and verbalizable, 'declarative' memory, which includes
      autobiographical memory. Autobiographical memory is weak in people with autistic
      spectrum disorder, who frequently turn to self-generated sensations for
      reassurance that they continue to exist. The author suggests that, instead of
      internalizing shared experiences leading to growth, children with autism can feel
      that they add to themselves by taking over the qualities of others through the
      'annexation' of physical properties that leads to a damaged object and can
      trigger a particular sort of negative therapeutic reaction. Clinical
      illustrations drawn from the treatment of two children on the autistic spectrum
      illustrate some ramifications of these processes in relation to the sense of a
      separate identity and the capacity to access memories.

PMID- 22471638
TI  - Intersubjectivity and dialecticism.

PMID- 22471637
TI  - Will psychoanalysis fulfill its promise?
AB  - Although Freud had aspirations of a university structure for psychoanalytic
      education the sociopolitical structure of the Austro-Hungarian empire precluded
      this, and psychoanalysis developed by default in the central European heartland
      within a part-time, private-practice educational structure. With its rapid spread
      in the post-World-War-II United States, and its ready penetration of American
      academic psychiatry, a counter educational structure arose in some quarters: the
      department-of-psychiatry-affiliated institute within the medical school. This
      article outlines beyond these other, more ambitious, academic vistas (the David
      Shakow model, the Anna Freud model, the Menninger Foundation, Emory University
      (USA), AP de BA (Argentina)); conceptions even closer to the ideal (idealized)
      goal of full-time placement within the university, with strong links to medicine,
      to the behavioral sciences and to the humanities. The putative advantages of such
      a structure are presented.

PMID- 22471639
TI  - The therapeutic action of psychoanalysis.
AB  - Psychoanalysis does not seek to get rid of symptoms but to question them as
      witnesses of psychic functioning and as formations of the unconscious. Whatever
      their nature may be, it is a question of analysing their causes and their
      functions as they appear and develop during the course of the analytic process.
      The latter is activated by the transference relationship induced by the method
      within a specific setting. The aim is to bring about liberating psychic
      transformations. The extension of the indications and modifications in the
      expression of psychic suffering have led to the development of psychotherapies.
      Their relations with psychoanalysis proper have been evolving constantly since
      the first advances by Ferenczi. This long historical evolution has resulted in
      their redefinition. Psychoanalytic practices are currently considered to require,
      depending on the case, different settings and different modes of psychic
      involvement from the analyst. Contemporary psychoanalysis places emphasis on the
      internal setting of the analyst (thus his training), analysis of the
      countertransference, and the risk of anti-analytic aberrations.

PMID- 22471640
TI  - On: response to Moran Shoham.

PMID- 22471641
TI  - Parenting imperfection: unlocking meaning in the developing relationship between
      a father and his disabled son, in Gianni Amelio's The Keys to the House.

PMID- 22471642
TI  - Leo Rangell 1913-2011.

PMID- 22471643
TI  - Hanna Segal 1918-2011.

PMID- 22471644
TI  - Functional capacity following univentricular repair--midterm outcome.
AB  - OBJECTIVE: Previous studies have seldom compared functional capacity in children
      following Fontan procedure alongside those with Glenn operation as destination
      therapy. We hypothesized that Fontan circulation enables better midterm
      submaximal exercise capacity as compared to Glenn physiology and evaluated this
      using the 6-minute walk test. DESIGN AND PATIENTS: Fifty-seven children aged 5-18
      years with Glenn (44) or Fontan (13) operations were evaluated with standard 6
      minute walk protocols. RESULTS: Baseline SpO(2) was significantly lower in Glenn
      patients younger than 10 years compared to Fontan counterparts and similar in the
      two groups in older children. Postexercise SpO(2) fell significantly in Glenn
      patients compared to the Fontan group. There was no statistically significant
      difference in baseline, postexercise, or postrecovery heart rates (HRs), or 6
      minute walk distances in the two groups. Multiple regression analysis revealed
      lower resting HR, higher resting SpO(2) , and younger age at latest operation to
      be significant determinants of longer 6-minute walk distance. Multiple regression
      analysis also established that younger age at operation, higher resting SpO(2) ,
      Fontan operation, lower resting HR, and lower postexercise HR were significant
      determinants of higher postexercise SpO(2) . Younger age at operation and
      exercise, lower resting HR and postexercise HR, higher resting SpO(2) and
      postexercise SpO(2) , and dominant ventricular morphology being left ventricular
      or indeterminate/mixed had significant association with better 6-minute work on
      multiple regression analysis. Lower resting HR had linear association with longer
      6-minute walk distances in the Glenn patients. CONCLUSIONS: Compared to Glenn
      physiology, Fontan operation did not have better submaximal exercise capacity
      assessed by walk distance or work on multiple regression analysis. Lower resting
      HR, higher resting SpO(2) , and younger age at operation were factors uniformly
      associated with better submaximal exercise capacity.

PMID- 22471645
TI  - Is mitochondrial tRNA Leu(UUR) 3291T>C mutation pathogenic?
AB  - According to a recent report by Sunami et al., a maternally inherited Japanese
      family with variable phenotypes including mitochondrial myopathy, recurrent
      headache, and myoclonus and epilepsy had been described to be associated with
      mitochondrial tRNA(Leu(UUR)) 3291T>C mutation. In order to verify this
      association, we reanalyzed the clinical and molecular datasets obtained from
      Sunami's work; in addition, a phylogenetic approach was employed to evaluate the
      conservation index of this mutation among different species. We further utilized
      RNA Fold Web Server to predict the minimum free energy (MFE) of tRNA(Leu(UUR))
      gene with and without this mutation. Most strikingly, a low level of conservation
      was found regarding 3291T>C mutation and a slight change in MFE had been observed
      between the wild type and the mutant. Our negative results gave no support for an
      active role for this mutation on the clinical expression of mitochondrial
      disorders.

PMID- 22471646
TI  - Complete mitochondrial genome of the Walking goby Scartelaos histophorus
      (Perceformes, Gobiidae).
AB  - The Walking goby Scartelaos histophorus (Perciformes, Gobiidae) is an amphibious
      gobioid fish. In this paper, the complete mitochondrial genome of S. histophorus
      was first determined. The genome is 16,496 bp in length and consists of 13
      protein-coding genes, 22 tRNA genes, 2 ribosomal RNA genes, and 1 control region.
      The overall base composition of S. histophorus is 27.5% for T, 28.0% for C, 28.3%
      for A, and 16.1% for G, with a slight A+T bias of 55.8%. It has the typical
      vertebrate mitochondrial gene arrangement.

PMID- 22471647
TI  - The complete mitochondrial genome of grouse locust Tetrix japonica (Insecta:
      Orthoptera: Tetrigoidea).
AB  - We have determined the complete mitochondrial genome of a species of grouse
      locust, Tetrix japonica. The total length of the T. japonica mitogenome is 15,128
      bp with 75.57% A+T content. It consists of 13 protein-coding, 22 transfer RNA
      (tRNA), and 2 ribosomal RNA (rRNA) genes, and an A+T-rich region. The A+T-rich
      region was located between the small rRNA and tRNA-Ile genes and is 531 bp in
      length.

PMID- 22471648
TI  - Oxygen and anesthesia: what lung do we deliver to the post-operative ward?
AB  - Anesthesia is safe in most patients. However, anesthetics reduce functional
      residual capacity (FRC) and promote airway closure. Oxygen is breathed during the
      induction of anesthesia, and increased concentration of oxygen (O(2) ) is given
      during the surgery to reduce the risk of hypoxemia. However, oxygen is rapidly
      adsorbed behind closed airways, causing lung collapse (atelectasis) and shunt.
      Atelectasis may be a locus for infection and may cause pneumonia. Measures to
      prevent atelectasis and possibly reduce post-operative pulmonary complications
      are based on moderate use of oxygen and preservation or restoration of FRC. Pre
      oxygenation with 100% O(2) causes atelectasis and should be followed by a
      recruitment maneuver (inflation to an airway pressure of 40 cm H(2) O for 10 s
      and to higher airway pressures in patients with reduced abdominal compliance
      (obese and patients with abdominal disorders). Pre-oxygenation with 80% O(2) may
      be sufficient in most patients with no anticipated difficulty in managing the
      airway, but time to hypoxemia during apnea decreases from mean 7 to 5 min. An
      alternative, possibly challenging, procedure is induction of anesthesia with
      continuous positive airway pressure/positive end-expiratory pressure to prevent
      fall in FRC enabling use of 100% O(2) . A continuous PEEP of 7-10 cm H(2) O may
      not necessarily improve oxygenation but should keep the lung open until the end
      of anesthesia. Inspired oxygen concentration of 30-40%, or even less, should
      suffice if the lung is kept open. The goal of the anesthetic regime should be to
      deliver a patient with no atelectasis to the post-operative ward and to keep the
      lung open.

PMID- 22471649
TI  - Validation of bimanual-coordinated training supported by a new upper-limb
      rehabilitation robot: a near-infrared spectroscopy study.
AB  - PURPOSE: Our previous work proposed a rehabilitation robot to support bimanual
      coordinated training not only in active-assisted and passive-driven modes but
      also in active-resisted mode. However, assessment of training effect was only
      focused on the improvements of subjects' motion-tracking precisions. This paper
      presents an evaluation strategy based on variations in both cerebral activation
      level (CAL) and motion-tracking precision. METHOD: Fourteen healthy subjects
      participated in motion-tracking training in bimanual active-assisted and active
      resisted modes, and in single right-limb and left-limb modes, with haemoglobin
      concentration and motion-tracking errors being measured simultaneously. Analyses
      of variance (ANOVA) of the CAL and motion-tracking errors were performed to
      investigate bimanual training effect and the difference between bimanual and
      single-limb trainings in activating the brain. RESULTS: In the bimanual modes,
      both the CAL and motion-tracking precision significantly increased after
      training. And the CAL induced in the bimanual trainings were significantly
      greater than in the single-limb trainings. CONCLUSIONS: Significant enhancement
      of the CAL and motion-tracking precision confirmed a positive training effect on
      enhancing the bimanual-coordination capability of healthy subjects. Compared to
      the single-limb modes, the higher CAL in the bimanual modes demonstrated the
      potential of the proposed bimanual training for improving the functional
      integrity of the two hemispheres.

PMID- 22471651
TI  - The effect of involved-field radiotherapy on survival in patients with early
      stage Hodgkin's lymphoma after autologous stem cell transplantation.

PMID- 22471650
TI  - Childhood obesity prevention in rural settings: background, rationale, and study
      design of '4-Health,' a parent-only intervention.
AB  - BACKGROUND: Childhood obesity in rural communities is a serious but understudied
      problem. The current experiment aims to assess a wide range of obesity risk
      factors among rural youth and to offer an 8-month intervention program for
      parents to reduce obesity risk in their preteen child. METHODS/DESIGN: A two
      group, repeated measures design is used to assess the effectiveness of the 4
      Health intervention program. Assessments include anthropometric measures, child
      self-evaluations, parent self-evaluations, and parent evaluations of child.
      County Extension agents from 21 rural Montana counties recruit approximately 150
      parent-child dyads and counties are semi-randomly assigned to the active
      intervention group (4-Health Educational Program) or a "best-practices" (Healthy
      Living Information) control group. DISCUSSION: This study will shed light on the
      effectiveness of this parent-only intervention strategy in reducing obesity risk
      factors among rural preteens. The 4-Health program is designed to provide
      information and skills development for busy rural parents that will increase
      healthy lifestyles of their preteen children and improve the parents' ability to
      intervene effectively in the lives of their families during this critical
      developmental period. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01510587.

PMID- 22471652
TI  - Genotypic and phenotypic characterization of Bordetella pertussis strains used in
      different vaccine formulations in Latin America.
AB  - AIM: To characterize Bordetella pertussis vaccine strains in comparison with
      current circulating bacteria. METHODS AND RESULTS: Genomic and proteomic analyses
      of Bp137 were performed in comparison with other vaccine strains used in Latin
      America (Bp509 and Bp10536) and with the clinical Argentinean isolate Bp106.
      Tohama I strain was used as reference strain. Pulse-field gel electrophoresis
      (PFGE) and pertussis toxin promoter (ptxP) sequence analysis revealed that Bp137
      groups with Bp509 in PFGE group III and contains ptxP2 sequence. Tohama I (group
      II) and Bp10536 (group I) contain ptxP1 sequence, while Bp106 belongs to a
      different PFGE cluster and contains ptxP3. Surface protein profiles diverged in
      at least 24 peptide subunits among the studied strains. From these 24
      differential proteins, Bp10536 shared the expression of ten proteins with Tohama
      I and Bp509, but only three with Bp137. In contrast, seven proteins were detected
      exclusively in Bp137 and Bp106. CONCLUSIONS: Bp137 showed more features in common
      with the clinical isolate Bp106 than the other vaccine strains here included.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results presented show that the old
      strains included in vaccines are not all equal among them. These findings
      together with the data of circulating bacteria should be taken into account to
      select the best vaccine to be included in a national immunization programme.

PMID- 22471653
TI  - Evaluation of a combined treatment paradigm consisting of environmental
      enrichment and the 5-HT1A receptor agonist buspirone after experimental traumatic
      brain injury.
AB  - Environmental enrichment (EE) and serotonin(1A) (5-HT(1A))-receptor agonists
      provide significant benefit after experimental traumatic brain injury (TBI). The
      aim of this study was to test the hypothesis that combining these therapies would
      produce an effect that is more robust than either therapy alone. Anesthetized
      adult male rats received a cortical impact or sham injury and then were randomly
      assigned to EE or standard (STD) housing where they received either buspirone
      (0.3 mg/kg) or vehicle (1.0 mL/kg) once daily for 3 weeks. Motor and cognitive
      assessments were conducted on post-injury days 1-5 and 14-19, respectively. CA1/3
      neurons were quantified at 3 weeks. No differences were observed among buspirone
      and vehicle sham groups in any task regardless of housing condition and thus the
      data were pooled. CA3 cell loss was reduced in the TBI+EE+buspirone and
      TBI+EE+vehicle groups. Motor recovery, spatial learning, and memory retention
      were enhanced in the TBI+EE+buspirone, TBI+EE+vehicle, and TBI+STD+buspirone
      groups versus the TBI+STD+vehicle group (p <= 0.005). Moreover, spatial learning
      was significantly better in the TBI+EE+buspirone group versus the
      TBI+STD+buspirone group (p<0.0001). No differences were revealed between the
      buspirone and vehicle EE groups. These data show that EE and buspirone benefit
      functional outcome after TBI, but their combination is not more robust than
      either alone, which does not support the hypothesis. The lack of an additive
      effect may be due to the early-and-continuous EE paradigm on its own producing
      marked benefits, resulting in a ceiling effect. The evaluation of buspirone in a
      delayed-and-abbreviated EE paradigm is ongoing in our laboratory.

PMID- 22471654
TI  - Retroperitoneal laparoscopic reconstruction for retrocaval ureter: experience and
      literature review.
AB  - PURPOSE: We describe surgical techniques and experience with retroperitoneal
      laparoscopic pyeloureterostomy in five cases of retrocaval ureter (RU). We also
      report the laparoscopic approach reconstruction for RU from peer-reviewed
      publications. PATIENTS AND METHODS: Five patients with RU underwent
      retroperitoneal laparoscopic pyeloureterostomy. Nuclear renography, intravenous
      urography (IVU), and ultrasonography follow-up was performed postoperatively.
      Science Citation Index searches were conducted to identify laparoscopic
      reconstruction for RU outcomes. Studies published after 1994 were included in the
      analysis. RESULTS: Operations were completed successfully and without
      complications in five patients. The mean operative time was 90.2 +/- 34.4
      minutes. The mean time needed to insert the Double-J stent and reanastomosis was
      51.2 +/- 11.4 minutes. Blood loss was minimal. Over a follow-up of 12 to 37
      months, hydronephrosis was found to decrease substantially. There were 24 peer
      reviewed studies covering a total of 62 patients suitable for inclusion in our
      final analysis. The most common method for reconstruction of the ureter was
      ureteroureterostomy, followed by pyeloureterostomy and pyelopyelotomy.
      CONCLUSION: Retroperitoneal laparoscopy for RU is a safe and effective procedure
      that should be considered as a first-line treatment for patients with this
      anatomic anomaly.

PMID- 22471655
TI  - Successful treatment of pediatric nail psoriasis with periodic pustular eruption
      using topical indigo naturalis oil extract.
AB  - Psoriasis of the nail greatly affects quality of life because of the difficulty
      in achieving long-lasting remission. Pustular psoriasis of the nail apparatus is
      characterized by the formation of sterile pustules, starting on one or two
      fingers or less often on the toes, and spontaneous improvement has rarely been
      observed. This case presents a girl with refractory nail psoriasis accompanied by
      periodic pustular eruption that responded well to topical treatment with indigo
      naturalis oil extract drops, achieving a remission of longer than 1 year.

PMID- 22471657
TI  - Hybrid metal/organo relay catalysis enables enynes to be latent dienes for
      asymmetric Diels-Alder reaction.
AB  - The hybrid Au(I)/Bronsted acid binary catalyst system enables enynes to serve as
      latent 1,3-silyloxydienes capable of participating in the first cascade
      hydrosiloxylation of an enynyl silanol/asymmetric Diels-Alder reaction. A variety
      of polycyclic compounds bearing multistereogenic centers were obtained in high
      yields and excellent enantioselectivities from the relay catalytic cascade
      reaction between (2-(but-3-en-1-ynyl)phenyl) silanols and quinones catalyzed by
      the combined achiral gold complex and chiral N-triflyl phosphoramide.

PMID- 22471658
TI  - Editorial comment: Inpatient safety trends in laparoscopic and open nephrectomy
      for renal tumours.

PMID- 22471659
TI  - Half-integer spin heptanuclear single-molecule magnet with an unusual
      Mn(III)6Mn(II) exchange-coupled core.
AB  - The synthesis, X-ray crystallography, magnetic properties, and high-field
      electron paramagnetic resonance (HFEPR) of a new heptanuclear manganese complex
      [Mn(7)(heamp)(6)](ClO(4))(2).4CH(2)Cl(2).H(2)O (complex 2), in which heampH(3) is
      2-[N,N-di(2-hydroxyethyl)aminomethyl]phenol (compound 1), is reported. Complex 2
      has a hexagonal, disk-shaped topology and contains six Mn(III) ions and a central
      Mn(II) ion. It crystallizes in the monoclinic space group P2(1)/c with two
      molecular orientations. Consideration of the cluster topology, together with
      variable-temperature and variable-field DC magnetic susceptibility data, suggest
      that complex 2 exists in a half-integer, S = (19)/(2) +/- 1 spin ground state,
      with appreciable uniaxial zero-field splitting (D = -0.16 cm(-1)). AC magnetic
      susceptibility measurements clearly show out-of-phase signals, which are
      frequency- and temperature-dependent, indicating slow magnetization relaxation
      behavior. An analysis of the relaxation data employing the Arrhenius formula
      yielded an effective relaxation barrier of 12.9 cm(-1). Simulations of HFEPR
      studies agree with the assignment of an S ~ (19)/(2) spin ground state, with g =
      1.96, D = -4.71 GHz (-0.16 cm(-1)), and a longitudinal fourth-order zero-field
      splitting parameter B(4)(0) = -2.7 * 10(-4) GHz (-9.0 * 10(-6) cm(-1)).

PMID- 22471660
TI  - Enhancing the usability and performance of structured association mapping
      algorithms using automation, parallelization, and visualization in the GenAMap
      software system.
AB  - BACKGROUND: Structured association mapping is proving to be a powerful strategy
      to find genetic polymorphisms associated with disease. However, these algorithms
      are often distributed as command line implementations that require expertise and
      effort to customize and put into practice. Because of the difficulty required to
      use these cutting-edge techniques, geneticists often revert to simpler, less
      powerful methods. RESULTS: To make structured association mapping more accessible
      to geneticists, we have developed an automatic processing system called Auto-SAM.
      Auto-SAM enables geneticists to run structured association mapping algorithms
      automatically, using parallelization. Auto-SAM includes algorithms to discover
      gene-networks and find population structure. Auto-SAM can also run popular
      association mapping algorithms, in addition to five structured association
      mapping algorithms. CONCLUSIONS: Auto-SAM is available through GenAMap, a front
      end desktop visualization tool. GenAMap and Auto-SAM are implemented in JAVA;
      binaries for GenAMap can be downloaded from http://sailing.cs.cmu.edu/genamap.

PMID- 22471662
TI  - Therapeutic targeting of BCR-ABL: prognostic markers of response and resistance
      mechanism in chronic myeloid leukaemia.
AB  - Chronic myeloid leukemia (CML) is caused by the formation of the BCR-ABL fusion
      protein as a result of the t(9;22) chromosomal translocation. The elucidation of
      its molecular pathogenesis led to the identification of a therapeutic target and
      the subsequent synthesis and introduction of a small-molecule inhibitor for this
      target, imatinib. Because CML is the first disease successfully treated by
      targeted kinase inhibition, it served as a paradigm for discovery of disease
      mechanism and drug development in other diseases in which constitutive kinase
      expression plays a central role in pathogenesis. Despite the spectacular success
      of imatinib, not all CML patients derive great benefit from it. This review will
      cover some of the currently known prognostic markers of disease response and
      potential resistance mechanisms.

PMID- 22471663
TI  - Therapeutic targeting of the epidermal growth factor receptor in human cancer.
AB  - The epidermal growth factor receptor (EGFR; also referred to as HER1 or ERBB1),
      is a member of the type 1 receptor tyrosine kinase family known as the ERBB
      family. Comprising 4 members-ERBB1, ERBB2 (also known as HER2), ERBB3 (HER3), and
      ERBB4 (HER4)-these receptors play a principal role in allowing cells to integrate
      and respond correctly to diverse external stimuli, ranging from soluble endocrine
      and paracrine factors to signaling molecules on neighboring cells. The cell must
      interpret these extracellular signals to produce an appropriate developmental or
      proliferative response, and aberrant activation of the kinase activity of these
      receptors, particularly EGFR and ERBB2, is important in the development and
      progression of human cancer. Given its roles in signal transduction and
      development of the malignant phenotype, EGFR has emerged as a critical target for
      therapeutic development against various forms of cancer. This review focuses on
      the current therapeutic approaches directed against EGFR, the emerging challenges
      of EGFR therapy resistance, and how our increasing knowledge of EGFR biology is
      driving more targeted or alternative approaches to cancer therapies.

PMID- 22471661
TI  - Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene
      amplified breast cancer: mechanisms and clinical implications.
AB  - Approximately 25% of human breast cancers overexpress the HER2 (ErbB2) proto
      oncogene, which confers a more aggressive tumor phenotype and associates with a
      poor prognosis in patients with this disease. Two approved therapies targeting
      HER2, the monoclonal antibody trastuzumab and the tyrosine kinase inhibitor
      lapatinib, are clinically active against this type of breast cancer. However, a
      significant fraction of patients with HER2+ breast cancer treated with these
      agents eventually relapse or develop progressive disease. This suggests that
      tumors acquire or possess intrinsic mechanisms of resistance that allow escape
      from HER2 inhibition. This review focuses on mechanisms of intrinsic and/or
      acquired resistance to HER2-targeted therapies that have been identified in
      preclinical and clinical studies. These mechanisms involve alterations to HER2
      itself, coexpression or acquisition of bypass signaling through other receptor or
      intracellular signaling pathways, defects in mechanisms of cell cycle regulation
      or apoptosis, and host factors that may modulate drug response. Emerging clinical
      evidence already suggests that combinations of therapies targeting HER2 as well
      as these resistance pathways will be effective in overcoming or preventing
      resistance.

PMID- 22471664
TI  - Antiangiogenic therapies targeting the vascular endothelia growth factor
      signaling system.
AB  - Angiogenesis is critical to the growth of human tumors and the development of
      metastasis. Amongst the many proangiogenic mechanisms identified, the vascular
      endothelial growth factor (VEGF) signaling pathway has been implicated as the key
      regulator of tumor neovascularisation. Various therapeutic agents targeting the
      VEGF pathway have been successfully developed, with many now approved and in
      routine clinical use. In general, VEGF-mediated angiogenesis can be inhibited by
      2 approaches: antibodies directed against VEGF ligands or VEGF receptors (VEGFRs)
      and tyrosine kinase inhibitors targeting the VEGFRs. Thus far, clinical benefits
      achieved with VEGF-targeted agents are limited by their modest efficacy and the
      development of resistance. With no shortage of drugs in development, the lack of
      well-validated biomarkers to predict for response or resistance to VEGF-directed
      therapies is now becoming a key factor limiting the further rational development
      of this class of anticancer agent. This review discusses the biology of VEGF
      signaling, the clinical efficacy of VEGF-targeting therapies, potential
      mechanisms of resistance, and emerging predictive biomarkers.

PMID- 22471665
TI  - Targeting PI3 kinase/AKT/mTOR signaling in cancer.
AB  - The phosphatidylinositol 3 kinase (PI3K) pathway is one of the major pathways
      modulating cell growth, proliferation, metabolism, survival, and angiogenesis.
      Hyperactivation of this pathway is one of the most frequent occurrences in human
      cancer and is thus an obvious target for treatment of this disease. Currently
      there are 26 novel compounds targeting the PI3K pathway being assessed in more
      than 150 cancer-related clinical trials. Although this pathway is involved in
      many vital biologic functions, data emanating from these clinical trials indicate
      that these drugs are well tolerated. This review outlines the interaction of the
      PI3K pathway with other signaling cascades, highlights mechanisms involved in
      hyperactivation, discusses current therapeutics in cancer-related clinical trials
      that target this pathway, and, based on preclinical data, discusses possible
      leads on patient selection and combinational therapy, including targeting
      multiple components of the associated signaling network.

PMID- 22471666
TI  - Aberrant B-Raf signaling in human cancer -- 10 years from bench to bedside.
AB  - The Ras/Raf/MEK/ERK signaling pathway plays a key role in physiological processes
      and is often dysregulated in cancer as well as developmental disorders such as
      the neuro-cardio-facio-cutaneous syndromes. Raf proteins, and in particular B
      Raf, represent an important regulatory node, which is reflected by the fact that
      B-Raf represents the most frequently mutated protein kinase gene in human tumors.
      Many genetic aberrations of the BRAF proto-oncogene, such as different point
      mutations and chromosomal rearrangements, have been reported since 2002. As B-Raf
      displays aberrant activity in tumor entities for which no or only limited
      effective therapies are available, e.g., melanoma, ovarian, and colorectal
      carcinoma, a lot of hope and effort has been placed on strategies inhibiting its
      activity. Indeed, recent clinical trials involving B-Raf selective inhibitors
      exhibited unprecedented response rates in metastatic melanoma patients. However,
      this therapeutic response is short-lived due to the emergence of several
      resistance mechanisms. Here we provide a review of our current knowledge on the
      regulation of this kinase under physiological circumstances and how this control
      is lost by mutations. We give an update on malignancies displaying high
      frequencies of BRAF mutations and discuss the mechanisms underlying the side
      effects and drug resistance phenomena associated with Raf inhibitors.

PMID- 22471667
TI  - Targeting the human kinome for cancer therapy.

PMID- 22471668
TI  - Naltrexone in the treatment of opioid-dependent pregnant women: the case for a
      considered and measured approach to research.
AB  - The present paper considers naltrexone to treat opioid dependence during
      pregnancy. The public health problem of opioid dependence and its treatment
      during pregnancy is reviewed first. Next, the naltrexone and opioid dependence
      treatment literature is summarized, with overviews of the pre-clinical and
      clinical research on prenatal naltrexone exposure. Finally, considerations and
      recommendations for future medication research for the treatment of opioid
      dependence in pregnant women are provided. The efficacy of long-acting injectable
      naltrexone relative to placebo, its blockade of opioid agonist euphoric effects,
      its lack of abuse and tolerance development and its modest adverse effect profile
      make it a potential medication for opioid-dependent pregnant women. However, it
      is not without seriously concerning potential drawbacks, including the difficulty
      surrounding medication induction that may lead to vulnerability with regard to
      relapse, physical dependence re-establishment, increased risk behaviors,
      treatment dropout and resulting opioid overdose. Before embarking on future
      research with this medication, the benefits and risks for the mother
      embryo/fetus/child dyad should be weighed carefully. Should future research be
      conducted, a multi-level commitment to proactive ethical research is needed to
      reach the ultimate goal of improving the lives of women and children affected by
      opioid dependence.

PMID- 22471669
TI  - Acute dyspnea in a young man with an old sternotomy.
AB  - Described is a 42-year-old man with complex congenital heart disease with single
      ventricle physiology who underwent a Fontan operation at 27 years of age. He
      presented with sudden-onset chest pain and dyspnea and was initially misdiagnosed
      with a pulmonary embolism. This case is described in order to highlight the
      challenges in the evaluation of common presentations in adults with congenital
      heart disease.

PMID- 22471670
TI  - Inner vane fringes of barn owl feathers reconsidered: morphometric data and
      functional aspects.
AB  - It is a challenge to understand how barn owls (Tyto alba) reduce noise during
      flight to be able to hunt small mammals by audition. Several specializations of
      the wing and the wing feathers have been implicated in noise reduction. What has
      been overlooked so far are the fringes at the inner vanes of remiges. We
      demonstrated, by using precise imaging techniques combined with morphometric
      measurements and air-flow studies, that these fringes merge into neighboring
      feather vanes by gliding into the grooves at the lower wing surface that are
      formed by parallel-oriented barb shafts. The connection of adjacent feathers
      results in a smooth lower wing surface and thus reduces sharp and noisy edges.
      This finding sheds new light on the mechanisms underlying noise reduction of
      flying owls.

PMID- 22471671
TI  - Preventing oropharyngeal injury during videolaryngoscopy and intubation.

PMID- 22471672
TI  - Injury survey of a non-traditional 'soft-edged' trampoline designed to lower
      equipment hazards.
AB  - In Australia trampolines contribute one quarter of all childhood play equipment
      injuries. The objective of this study was to gather and evaluate injury data from
      a non-traditional, 'soft-edged', consumer trampoline, where the design aimed to
      minimise injuries from the equipment and from falling off. The manufacturer of
      the non-traditional trampoline provided the University of Technology Sydney with
      their Australian customer database. The study involved surveys in Queensland and
      New South Wales, between May 2007 and March 2010. Initially injury data was
      gathered by a phone interview pilot study, then in the full study, through an
      email survey. The 3817 respondents were the carers of child users of the 'soft
      edge' trampolines. Responses were compared with Australian and US emergency
      department data. In both countries the proportion of injuries caused by the
      equipment and falling off was compared with the proportion caused by the jumpers
      to themselves or each other. The comparisons showed a significantly lower
      proportion resulted from falling-off or hitting the equipment for this design
      when compared to traditional trampolines, both in Australia and the US. This
      research concludes that equipment-induced and falling-off injuries, the more
      severe injuries on traditional trampolines, can be significantly reduced with
      appropriate trampoline design.

PMID- 22471673
TI  - Growth dynamics of barium titanate thin films on polycrystalline Ni foils using
      polymer-assisted deposition technique.
AB  - Polymer-assisted deposition (PAD) technique was developed to fabricate
      ferroelectric BaTiO(3) (BTO) thin films directly on polycrystalline nickel foils.
      The growth dynamics was systematically studied to optimize the single-phase BTO
      films with good dielectric properties. It is critical to pretreat nickel foils
      with hydrogen peroxide (H(2)O(2)) solution to form thin nickel oxide layers on
      the surfaces for the growth of BTO films. Both the concentration of H(2)O(2)
      solution and the pretreated time were found to strongly affect the dielectric
      constant of BTO films, which may be associated with the oxygen diffusion from
      nickel oxide buffer layers to BTO layers during annealing. The BTO thin films
      with optimized growth conditions have good crystal structure and electrical
      properties, suggesting that the as-grown BTO films by PAD technique can be
      utilized for new devices development and energy storage applications.

PMID- 22471674
TI  - Isolated bronchiolitis obliterans: high incidence and diagnosis following
      terrorist attacks.

PMID- 22471675
TI  - In praise of paper journals.

PMID- 22471676
TI  - On the invention of disease.

PMID- 22471677
TI  - The relevance of the epidemiology of human sex ratios at birth to some medical
      problems.
AB  - The human sex ratio (proportion male at birth) shows considerable variation which
      is central to reproductive epidemiology. For example, it has reportedly shown
      significant secular trends and wartime variation, and it has shown replicated
      variation with parental exposure to several deleterious chemicals. However,
      scientific progress in identifying the causes of these forms of variation has
      been very slow and, as described here, this has elicited some scepticism.
      Benefits may be expected from identifying these causes. Two (non-competing)
      hypotheses have emerged, the first relating to the hormonal regulation of sex
      ratio at conception, and the second to the sex-selective effects of stressors
      during pregnancy. It is shown here that if the first of these hypotheses was
      substantially correct, it would illuminate a number of scientific and medical
      problems, for example, the causes of autism and of selected sex-related
      congenital malformations and obstetric pathologies.

PMID- 22471678
TI  - Secular trends in the epidemiology of pre-eclampsia throughout 40 years in
      Norway: prevalence, risk factors and perinatal survival.
AB  - Pre-eclampsia is a leading complication of pregnancy, associated with maternal
      and neonatal morbidity. The present study describes the epidemiology of pre
      eclampsia in Norway, with data from the Medical Birth Registry of Norway,
      covering 40 years. We aimed at describing time trends in prevalence, selected
      risk factors and perinatal mortality. We also analysed time trends in recurrence
      risk of total pre-eclampsia and pre-eclampsia with preterm delivery. A total of
      2,416,501 women giving birth during 1967-2008 were included. Prevalence of pre
      eclampsia increased from 1967 to 1999 and decreased thereafter, with an overall
      prevalence of 3%. Rates increased more over time among younger than older women,
      resulting in a significantly lower excess risk of pre-eclampsia associated with
      high maternal age in later years. For example, relative risk (RR) of pre
      eclampsia among primiparae aged >=35 relative to <25 years changed from 2.4 [95%
      confidence interval (CI) 2.1, 2.7] in 1967-1976 to 1.2 [95% CI 1.1, 1.3] in 1999
      2008. For recurrence risk, subsequent pregnancies to a mother were linked, with
      the mother being the unit of analysis. Recurrence risk of pre-eclampsia was high,
      particularly recurrence of preterm pre-eclampsia, with overall RR close to 50 of
      a second pregnancy with pre-eclampsia and preterm birth compared with women
      without pre-eclampsia in first pregnancies. Finally, stillbirth associated with
      pre-eclampsia decreased more than neonatal mortality over time, and in the last 5
      years only a moderate excess risk of stillbirth and neonatal death was observed.

PMID- 22471679
TI  - Predicting large fetuses at birth: do multiple ultrasound examinations and
      longitudinal statistical modelling improve prediction?
AB  - Predicting large fetuses at birth has long been a challenge in obstetric
      practice. We examined whether ultrasound examinations at multiple times during
      pregnancy improve the accuracy of prediction using repeated, longitudinal
      statistical modelling, and whether adding maternal characteristics improves the
      accuracy of prediction. We used data from a previous study conducted in Norway
      and Sweden from 1986 to 1989 in which each pregnant woman had four ultrasound
      examinations at around 17, 25, 33 and 37 weeks of gestation. At birth, infant
      size was classified as large-for-gestational age (LGA, >90th centile) and
      macrosomia (>4000 g) or not. We used a longitudinal random effects model with
      quadratic fixed and random effects to predict term LGA and macrosomia at birth.
      Receiver-operator curves and mean-squared error were used to measure accuracy of
      the prediction. Ultrasound examination around 37 weeks had the best accuracy in
      predicting LGA and macrosomia at birth. Adding multiple ultrasound examinations
      at earlier gestations did not improve the accuracy. Adjusting for maternal
      characteristics had limited impact on the accuracy of prediction. Thus, a single
      ultrasound examination at late gestation close to birth is the simplest method
      currently available to predict LGA and macrosomia.

PMID- 22471680
TI  - Antenatal haemoglobin A1c and risk of large-for-gestational-age infants in a
      multi-ethnic cohort of women with gestational diabetes.
AB  - Gestational diabetes mellitus (GDM) is a risk factor for delivering a large-for
      gestational-age (LGA) infant. Haemoglobin A1c (A1C) is an indicator of glycaemic
      control. The objective of this study was to test whether higher A1C quartile at
      the time of diagnosis of GDM is associated with increased risk of delivering a
      LGA or macrosomic infant. Women with singleton pregnancies treated for GDM at a
      large diabetes and pregnancy programme located in Charlotte, North Carolina, were
      eligible for inclusion in this retrospective cohort study. Clinical information,
      including A1C at diagnosis, treatment, prior medical and obstetric history, and
      birth data were abstracted from medical records. LGA was defined as birthweight
      >90th percentile for gestational age and sex and macrosomia as birthweight >4000
      g. Logistic regression was used to analyse the association of A1C at GDM
      diagnosis with risk of delivering LGA or macrosomic infants. This study included
      502 women. Prevalences of LGA and macrosomia were 4% and 6% respectively. After
      adjustment there was no detectable trend of increased risk for LGA (P for trend =
      0.12) or macrosomia (P for trend = 0.20) across increasing quartiles of A1C at
      GDM diagnosis. A1C at GDM diagnosis may not be linearly associated with LGA or
      macrosomia, possibly because of the mediating effect of strict glycaemic control
      in this clinical setting.

PMID- 22471681
TI  - Perinatal characteristics and risk of polio among Swedish twins.
AB  - Prenatal exposure to adverse environmental conditions is related to increased
      adult mortality in regions where infections are highly prevalent, yet there is
      little evidence of the impact of perinatal conditions on the risk of severe
      infections throughout life. Using prospectively collected data from 21 604 like
      sexed Swedish twins of known zygosity born in 1926-1958, we examined the risk of
      polio in relation to perinatal characteristics using cohort and nested co-twin
      case-control analyses. Polio incidence was determined through an interview in
      1998, and linkage with the Swedish national inpatient and death registries. There
      were 133 cases of polio. In the cohort analysis, birth length, birthweight and
      head circumference were positively associated with polio risk. After adjustment
      for sex, birth year, gestational age at birth and within-twin pair correlations,
      twins of shortest length (<44 cm) had a 67% ([95% CI: 6%, 88%]; P=0.04) lower
      risk of polio compared with the reference group (47-49 cm). After additional
      adjustment for birth length, every 100-g increase in birthweight was related to a
      34% increased risk of polio ([95% CI: -1%, 82%]; P=0.06), and every 10-mm
      increase in head circumference was related to a 17% greater risk of polio ([95%
      CI: 5%, 31%]; P=0.004). In co-twin control analyses among 226 disease-discordant
      twins, birth length, birthweight and head circumference were 0.3 cm (P=0.19), 84
      g (P=0.07) and 3 mm (P=0.08) higher in cases than controls, respectively. Similar
      associations were observed among monozygotic (n=84) and dizygotic (n=142) twins.
      These findings suggest that early intrauterine growth restriction may be
      inversely related to the incidence of polio.

PMID- 22471682
TI  - Time trends in socio-economic factors and risk of hospitalisation with infectious
      diseases in pre-school children 1985-2004: a Danish register-based study.
AB  - The purpose of this study was to examine socio-economic differences in the risk
      of hospitalisation among children aged 0-5 years in Denmark from 1985 to 2004.
      All children born between 1985 and 2004 (n=1,278,286) were followed for hospital
      admissions for infectious diseases from the 29th day of life until the children
      reached the age of 6 years or the end of 2004, whichever came first. Information
      on parental socio-economic position (education, labour market attachment and
      household income) was gathered through record linkage with administrative
      registries. Infections were grouped into upper respiratory, lower respiratory,
      gastrointestinal, ear and fever infections. The data were analysed using Cox
      regression. Children of parents on sick leave or early retirement had an
      increased risk of being hospitalised with an infection compared with children of
      employed parents. A clear inverse educational gradient in risk of offspring
      hospitalisation was also found. From 1985 to 2004 the inverse associations
      between parental education and risk of hospitalisation grew stronger, whereas the
      comparatively weaker association between household income and risk of offspring
      hospitalisation decreased in magnitude. The association between socio-economic
      status and hospitalisation was strongest for lower respiratory, gastrointestinal
      and ear infections. This study documented a socially patterned hospitalisation of
      pre-school children in Denmark. Future studies should investigate possible
      explanations for the increased risk among children from families with low socio
      economic status.

PMID- 22471683
TI  - Maternal education inequalities in height growth rates in early childhood: 2004
      Pelotas birth cohort study.
AB  - Socio-economic inequalities in attained height have been reported in many
      countries. The aim of this study was to explore the age at which maternal
      education inequalities in child height emerge among children from a middle-income
      country. Using data from the 2004 Pelotas cohort study from Brazil we modelled
      individual height growth trajectories in 2106 boys and 1947 girls from birth to 4
      years using a linear spline mixed-effects model. We examined the associations of
      maternal education with birth length and trajectories of growth in length/height,
      and explored the effect of adjusting for a number of potential confounder or
      mediator factors. We showed linear and positive associations of maternal
      education with birth length and length/height growth rates at 0-3 months and 12
      29/32 months with very little association at 3-12 months, particularly in boys.
      By age 4 years the mean height of boys was 101.06 cm (SE = 0.28) in the lowest
      and 104.20 cm (SE = 0.15) in the highest education category (mean difference 3.14
      cm, SE = 0.32, P < 0.001). Among girls the mean height was 100.02 cm (SE = 0.27)
      and 103.03 cm (SE = 0.15) in the lowest and highest education categories,
      respectively (mean difference 3.01 cm, SE = 0.31, P < 0.001). For both boys and
      girls there was on average a 3-cm difference between the extreme education
      categories. Adjusting for maternal height reduced the observed birth length
      differences across maternal education categories, but differences in postnatal
      growth rates persisted. Our data demonstrate an increase in the absolute and
      relative inequality in height after birth; inequality increases from
      approximately 0.2 standard deviations of birth length to approximately 0.7
      standard deviations of height at age 4, indicating that height inequality, which
      was already present at birth, widened through differential growth rates to age 2
      years.

PMID- 22471685
TI  - A biobank of primary teeth within the Norwegian Mother and Child Cohort Study
      (MoBa): a resource for the future.
AB  - The Norwegian Mother and Child Cohort Study (MoBa) is a prospective population
      based cohort study including >100 000 pregnancies and following the children
      through childhood, using questionnaires and collecting biological samples. The
      aim of MoBa is to test specific aetiological hypotheses by estimating the
      association between exposure and disease, aiming at prevention. A biobank for
      exfoliated primary teeth collected from the children participating in MoBa has
      been established (MoBaTooth Biobank). Samples of tooth tissues from the primary
      dentition can give information about exposure to toxic and essential elements
      during fetal life and early infancy. Prenatally and postnatally formed tooth
      tissues permanently document early exposures unlike other biomarkers, as teeth
      form incrementally at a known rate. Results from tooth analyses will be coupled
      with corresponding information in the multiple questionnaires and data from
      analysis of other biological samples collected by MoBa. Invitations to donate one
      or more teeth are sent to all mothers/children in the period 2008-2016, when the
      child is 6.75 years old. By August 2011, 7400 participants had been recorded into
      the MoBaTooth database donating altogether 9798 teeth (1.3 teeth per child). The
      response rate was 24%, but there is a lag of >1 year in the response. Data from
      the tooth biobank can supply MoBa with important additional information on the
      uptake of trace elements during fetal life and early infancy. This information
      can illuminate possible causal factors of health and disease in the future.

PMID- 22471684
TI  - California Very Preterm Birth Study: design and characteristics of the population
      and biospecimen bank-based nested case-control study.
AB  - Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and
      racial disparity in the US. The underlying causes of VPTB are multiple and poorly
      understood. The California Very Preterm Birth Study was conducted to discover
      maternal and infant genetic and environmental factors associated with VPTB. This
      paper describes the study design, population, data and specimen collection,
      laboratory methods and characteristics of the study population. Using a large,
      population-based cohort created through record linkage of livebirths delivered
      from 2000 to 2007 in five counties of southern California, and existing data and
      banked specimens from statewide prenatal and newborn screening, 1100 VPTB cases
      and 796 control mother-infant pairs were selected for study (385/200 White,
      385/253 Hispanic and 330/343 Black cases/controls, respectively). Medical record
      abstraction of cases was conducted at over 50 hospitals to identify spontaneous
      VPTB, improve accuracy of gestational age, obtain relevant clinical data and
      exclude cases that did not meet eligibility criteria. VPTB was defined as birth
      at <32 weeks in Whites and Hispanics and <34 weeks in Blacks. Approximately 55%
      of all VPTBs were spontaneous and 45% had medical indications or other
      exclusions. Of the spontaneous VPTBs, approximately 41% were reported to have
      chorioamnionitis. While the current focus of the California Very Preterm Birth
      Study is to assess the role of candidate genetic markers on spontaneous VPTB, its
      design enables the pursuit of other research opportunities to identify social,
      clinical and biological determinants of different types of VPTB with the ultimate
      aim of reducing infant mortality, morbidity and racial disparities in these
      health outcomes in the US and elsewhere.

PMID- 22471686
TI  - Attitudes of pregnant women towards collection of biological specimens during
      pregnancy and at birth.
AB  - Epidemiological investigations of maternal and child health may involve the
      collection of biological specimens, including cord blood and the placenta;
      however, the attitudes of pregnant women towards participation in the collection
      of biological specimens have been studied rarely. We evaluated attitudes towards
      collection and storage of biological specimens, and determined whether attitudes
      differed by maternal characteristics, in a cross-sectional study of pregnant
      women residing in Kent County, Michigan. Women were interviewed at their first
      visit for prenatal care between April and October 2006 (n = 311). Willingness to
      participate was highest for maternal blood collection (72%), followed by storage
      of biological specimens (68%), placenta collection (64%), and cord blood
      collection (63%). About one-quarter of women (25-28% by procedure) would not
      participate even if compensated. Hispanic ethnicity was associated with
      unwillingness to participate in maternal blood collection (OR = 2.16 [95% CI
      1.15, 4.04]). Primiparity was associated with unwillingness to participate in
      cord blood collection (OR = 1.72 [95% CI 1.23, 2.42]). Among women willing to
      participate, Hispanic women were less likely to require compensation; while
      higher educated, married and primiparous women were more likely to require
      compensation. In conclusion, while many pregnant women were willing to
      participate in biological specimen collection, some women were more resistant, in
      particular Hispanic and primiparous women. Targeting these groups of women for
      enhanced recruitment efforts may improve overall participation rates and the
      representativeness of participants in future studies of maternal and child
      health.

PMID- 22471687
TI  - Participation in population-based case-control studies: does the observed decline
      vary by socio-economic status?
AB  - An Australian study of childhood leukaemia (Aus-ALL) previously reported that
      control participation was positively associated with socio-economic status (SES).
      A similar study of childhood brain tumours (Aus-CBT) was carried out 4 years
      later, and this paper compares control participation and its relationship with
      SES in the two studies. To assess the representativeness of controls in terms of
      SES, the addresses of controls were linked to Australian Bureau of Statistics
      Census 2006 Collection Districts (CDs), and hence to area-based indices of SES.
      Independent sample t-tests and chi-squared tests were used to compare the SES
      indices of CDs where Aus-CBT controls lived with those where Aus-ALL controls
      lived and with those of all CDs where Australian families lived. The overall
      percentage of eligible families who agreed to participate was lower in Aus-CBT
      (53.9%) than in Aus-ALL (70.3%). Control families in both studies were of higher
      SES than the general population, while the distribution of SES among recruited
      controls was similar in both studies. These findings provide some reassurance
      that the observed decline in research participation over time may not be
      associated with an increasingly unrepresentative participant population.

PMID- 22471688
TI  - Epidemiological approaches to measure childhood stress.
AB  - The prevalence of childhood stress has repeatedly been shown to be high, with
      'parental separation' and 'being bullied at school' as the most frequently
      reported stressors in the child's everyday life. This is quite alarming as
      children are most vulnerable to the adverse psychological and physiological
      health consequences of chronic stress exposure. Despite growing research interest
      in this field over the last years, literature falls short in providing an
      overview of methods to adequately assess stress in elementary school children (6
      12 years old). This review describes questionnaires and interviews, as well as
      laboratory measurements of cortisol in biological samples (serum, urine, saliva
      and hair) as stress assessment methods in children, with the emphasis on
      epidemiological research settings. Major characteristics, strengths and
      limitations of these methods are established, examples of child-specific stressor
      questionnaires and interviews are provided and specific recommendations with
      respect to epidemiological research are formulated. In addition, hair cortisol as
      a potential biomarker for chronic stress (in children) is discussed more
      thoroughly. This review is meant to serve as a preliminary guide for health
      researchers new to this research area by reflecting on theoretical and
      methodological aspects in childhood stress assessment.

PMID- 22471689
TI  - Semi-automatic analysis of standard uptake values in serial PET/CT studies in
      patients with lung cancer and lymphoma.
AB  - BACKGROUND: Changes in maximum standardised uptake values (SUVmax) between serial
      PET/CT studies are used to determine disease progression or regression in
      oncologic patients. To measure these changes manually can be time consuming in a
      clinical routine. A semi-automatic method for calculation of SUVmax in serial
      PET/CT studies was developed and compared to a conventional manual method. The
      semi-automatic method first aligns the serial PET/CT studies based on the CT
      images. Thereafter, the reader selects an abnormal lesion in one of the PET
      studies. After this manual step, the program automatically detects the
      corresponding lesion in the other PET study, segments the two lesions and
      calculates the SUVmax in both studies as well as the difference between the
      SUVmax values. The results of the semi-automatic analysis were compared to that
      of a manual SUVmax analysis using a Philips PET/CT workstation. Three readers did
      the SUVmax readings in both methods. Sixteen patients with lung cancer or
      lymphoma who had undergone two PET/CT studies were included. There were a total
      of 26 lesions. RESULTS: Linear regression analysis of changes in SUVmax show that
      intercepts and slopes are close to the line of identity for all readers (reader
      1: intercept = 1.02, R2 = 0.96; reader 2: intercept = 0.97, R2 = 0.98; reader 3:
      intercept = 0.99, R2 = 0.98). Manual and semi-automatic method agreed in all
      cases whether SUVmax had increased or decreased between the serial studies. The
      average time to measure SUVmax changes in two serial PET/CT examinations was four
      to five times longer for the manual method compared to the semi-automatic method
      for all readers (reader 1: 53.7 vs. 10.5 s; reader 2: 27.3 vs. 6.9 s; reader 3:
      47.5 vs. 9.5 s; p < 0.001 for all). CONCLUSIONS: Good agreement was shown in
      assessment of SUVmax changes between manual and semi-automatic method. The semi
      automatic analysis was four to five times faster to perform than the manual
      analysis. These findings show the feasibility of using semi-automatic methods for
      calculation of SUVmax in clinical routine and encourage further development of
      programs using this type of methods.

PMID- 22471690
TI  - Impact of pulmonary hypertension on transplant outcomes in pediatric
      cardiomyopathy patients.
AB  - Controversy exists over whether PHTN in heart transplant candidates increases
      post-transplant mortality. We performed analysis of data reported to UNOS for
      children who underwent primary heart transplantation for cardiomyopathy from
      January 1994 to June 2010. Patients were divided into two groups depending on
      their pre-transplant TPG: no-PHTN (TPG <= 12 mmHg) and PHTN (TPG >12 mm Hg). A
      total of 6139 children underwent transplantation of whom 2456 (40%) were for
      cardiomyopathies; 1322 (54%) of these had catheterization data available. The
      PHTN group (mean TPG 19.5 +/- 8.6) had 312 patients and no-PHTN (TPG 6.7 +/- 4.0)
      had 1010. Mortality at one month (4.5% vs. 2.3%) and three months (6.1% vs. 3.1%)
      post-transplant was significantly higher in the PHTN than the no-PHTN group with
      an odds ratio of 2 (p < 0.05). There was no significant effect of PHTN on early
      mortality in children <1 yr age. There was no significant improvement in early
      survival for transplants performed after compared to before 2003 in patients with
      PHTN despite availability of pulmonary dilators. Pre-transplant PHTN increases
      early post-transplant mortality in pediatric cardiomyopathy patients above one yr
      of age. There has been no significant improvement in the outcome of this group
      over the last seven yr.

PMID- 22471691
TI  - Staphylococcal control in the veterinary hospital.
AB  - Staphylococcal infections are common in veterinary dermatology patients, as are
      patients whose health status places them at increased risk of staphylococcal
      infection. The rapid emergence and dissemination of meticillin-resistant
      staphylococci has had significant impacts on management of infections and also
      increased concerns about transmission of staphylococci between animals, from
      animals to humans and from humans to animals. The increasing incidence and
      implications of staphylococcal infections, particularly meticillin-resistant
      staphylococcal infections, is leading to more interest in infection control in
      veterinary hospitals as a means to help reduce the impact of these significant
      pathogens. Infection control is a series of principles and practices that can and
      should be implemented by every veterinary hospital to improve patient care,
      protect personnel and meet the increasing expectations. Fortunately, general
      concepts of infection control are both simple and practical, and application of a
      basic infection control programme requires limited time, effort or training. With
      an understanding of some basic concepts and use of available resources,
      development of an effective infection control programme is within the reach of
      any facility.

PMID- 22471692
TI  - Drastic Au(111) surface reconstruction upon insulin growth factor tripeptide
      adsorption.
AB  - Adsorption of biomolecules at metal surfaces often creates two-dimensional
      ordering of the adlayers. However, metal substrate reconstruction is less
      commonly observed, unless upon annealing of the molecule-surface system. Here, we
      report on the drastic room-temperature reconstruction of the Au(111) surface,
      driven by the adsorption of insulin growth factor tripeptide molecules. Scanning
      tunneling microscopy images show that the surface reconstruction, which takes
      place without annealing the system, is dynamic and evolves over time. It is
      initiated at kinks and steps edges, but the reconstruction also takes place
      within defect-free terraces. Theoretical calculations are performed to explain
      the reconstruction at the molecular level.

PMID- 22471693
TI  - Putative resistance gene markers associated with quantitative trait loci for fire
      blight resistance in Malus 'Robusta 5' accessions.
AB  - BACKGROUND: Breeding of fire blight resistant scions and rootstocks is a goal of
      several international apple breeding programs, as options are limited for
      management of this destructive disease caused by the bacterial pathogen Erwinia
      amylovora. A broad, large-effect quantitative trait locus (QTL) for fire blight
      resistance has been reported on linkage group 3 of Malus 'Robusta 5'. In this
      study we identified markers derived from putative fire blight resistance genes
      associated with the QTL by integrating further genetic mapping studies with
      bioinformatics analysis of transcript profiling data and genome sequence
      databases. RESULTS: When several defined E.amylovora strains were used to
      inoculate three progenies from international breeding programs, all with 'Robusta
      5' as a common parent, two distinct QTLs were detected on linkage group 3, where
      only one had previously been mapped. In the New Zealand 'Malling 9' X 'Robusta 5'
      population inoculated with E. amylovora ICMP11176, the proximal QTL co-located
      with SNP markers derived from a leucine-rich repeat, receptor-like protein
      (MxdRLP1) and a closely linked class 3 peroxidase gene. While the QTL detected in
      the German 'Idared' X 'Robusta 5' population inoculated with E. amylovora strains
      Ea222_JKI or ICMP11176 was approximately 6 cM distal to this, directly below a
      SNP marker derived from a heat shock 90 family protein gene (HSP90). In the US
      'Otawa3' X 'Robusta5' population inoculated with E. amylovora strains Ea273 or
      E2002a, the position of the LOD score peak on linkage group 3 was dependent upon
      the pathogen strains used for inoculation. One of the five MxdRLP1 alleles
      identified in fire blight resistant and susceptible cultivars was genetically
      associated with resistance and used to develop a high resolution melting PCR
      marker. A resistance QTL detected on linkage group 7 of the US population co
      located with another HSP90 gene-family member and a WRKY transcription factor
      previously associated with fire blight resistance. However, this QTL was not
      observed in the New Zealand or German populations. CONCLUSIONS: The results
      suggest that the upper region of 'Robusta 5' linkage group 3 contains multiple
      genes contributing to fire blight resistance and that their contributions to
      resistance can vary depending upon pathogen virulence and other factors. Mapping
      markers derived from putative fire blight resistance genes has proved a useful
      aid in defining these QTLs and developing markers for marker-assisted breeding of
      fire blight resistance.

PMID- 22471694
TI  - Topical timolol for small hemangiomas of infancy.
AB  - Propranolol has become the treatment of choice of large and complicated infantile
      hemangiomas. There is a controversy concerning the safety of systemic
      propranolol. Here we show that topical use of the beta-blocker timolol can also
      inhibit the growth and promote regression of infantile hemangiomas. In this case
      series we treated 11 infantile hemangiomas in nine children including six preterm
      babies with the nonselective betablocker timolol. A timolol containing gel was
      manufactured from an ophthalmic formulation of timolol 0.5% eyedrops. This gel
      was applied using a standardized occlusive dressing (Finn-Chambers) containing
      approximately 0.25 mg of timolol. In all infants topical timolol was associated
      with growth arrest, a reduction in redness and thickness within the first 2
      weeks. Seven hemangiomas showed almost complete resolution, and four became much
      paler and thinner. No data are available on the transdermal absorption of
      timolol. Even supposing complete absorption of timolol from the occlusive
      dressing, a maximum dose of 0.25 mg of timolol would result per day and
      hemangioma. Regression of infantile hemangiomas treated using 0.5% timolol gel in
      this case series occurred earlier than spontaneous regression which is generally
      not observed before the age of 9-12 months. The promising results need to be
      verified in prospective randomized trials on topical beta blocker administration
      for infantile hemangiomas which should address dose, duration, and mode of
      application.

PMID- 22471695
TI  - Association between binge drinking, type of friends and gender: a cross-sectional
      study among Brazilian adolescents.
AB  - BACKGROUND: Hazardous drinking among adolescents is a major public health
      concern. The purpose of this study was to examine the prevalence of binge
      drinking/alcohol consumption and its association with different types of
      friendship networks, gender and socioeconomic status among students in Belo
      Horizonte, Minas Gerais, Brazil. METHODS: We conducted a cross-sectional study on
      a representative random sample of 891 adolescents (41% male, aged 15-19 years)
      from public and private schools in 2009-2010. Information on friendship networks
      and binge drinking was collected using two validated self-administered
      questionnaires: the Integrated Questionnaire for the Measurement of Social
      Capital and the first 3 items in the Alcohol Use Disorders Identification Test
      (AUDIT C). We used the area-based Social Vulnerability Index (SVI), mother and
      father's educational background, and the type of school to assess socioeconomic
      status. The chi-squared test was used to examine the associations between sample
      characteristics or the type of friends and binge drinking (p-values <0.05 were
      considered statistically significant). Ordinal logistic regression was used to
      estimate the association between binge drinking and the independent variables.
      RESULTS: A total of 321 (36%) adolescents reported binge drinking (5 or more
      drinks in one occasion), and among them, 233 (26.2%) adolescents reported binge
      drinking less than monthly to monthly, and 88 (9.9%) weekly to daily. Binge
      drinking was associated with being male (OR = 1.52, 95% CI 1.01-2.28) and with
      living in a low vulnerability area (having the best housing conditions,
      schooling, income, jobs, legal assistance and health) (OR = 1.66, 95% CI 1.05
      2.62). Students who reported that their closest friends were from school (as
      opposed to friends from church) had an increased risk of binge drinking (OR =
      3.55, 95% CI 1.91-5.87). In analyses stratified by gender, the association was
      significant only among the female students. CONCLUSIONS: The prevalence of binge
      drinking was high in this sample of Brazilian adolescents, and gender, low social
      vulnerability and friendship network were associated with binge drinking.

PMID- 22471696
TI  - Snail is an independent prognostic predictor for progression and patient survival
      of gastric cancer.
AB  - The present study investigated the clinical significance of Snail, a zinc-finger
      transcription factor, in the development and progression of gastric cancer. To
      elucidate the relationship between Snail expression and dedifferentiation status
      with cancer stem cell phenotype in gastric cancer cells, we used western blot
      analysis, RT-PCR, quantitative real-time PCR and flow cytometry.
      Immunohistochemistry staining and evaluation of Snail expression in 10 human
      normal gastric samples versus 103 clinicopathologically characterized gastric
      cancer tissues followed by statistical analyses were applied to evaluate the
      prognostic value of Snail expression for progression and patient survival of
      gastric carcinomas. The results showed that functional Snail expression
      interlinks dedifferentiation status with cancer stem cell phenotype in gastric
      cancer cells. In addition, expression levels of Snail in gastric cancer tissues
      were significantly associated with tumor cell differentiation, local tumor
      growth, lymph node status, distant metastasis and tumor stage. The overall
      survival rate of gastric cancer patients with high Snail expression was
      significantly lower than for those patients with low Snail expression.
      Multivariate Cox regression analyses showed that Snail expression is an
      independent prognostic predictor for patient survival of gastric carcinomas.
      Thus, our data suggest that Snail expression could be a reliable independent
      prognostic factor to predict gastric carcinoma progression, which might open a
      new avenue for potential clinical intervention with functional Snail expression
      in gastric cancer patients.

PMID- 22471697
TI  - Enhanced formation of aerenchyma and induction of a barrier to radial oxygen loss
      in adventitious roots of Zea nicaraguensis contribute to its waterlogging
      tolerance as compared with maize (Zea mays ssp. mays).
AB  - Enhancement of oxygen transport from shoot to root tip by the formation of
      aerenchyma and also a barrier to radial oxygen loss (ROL) in roots is common in
      waterlogging-tolerant plants. Zea nicaraguensis (teosinte), a wild relative of
      maize (Zea mays ssp. mays), grows in waterlogged soils. We investigated the
      formation of aerenchyma and ROL barrier induction in roots of Z. nicaraguensis,
      in comparison with roots of maize (inbred line Mi29), in a pot soil system and in
      hydroponics. Furthermore, depositions of suberin in the exodermis/hypodermis and
      lignin in the epidermis of adventitious roots of Z. nicaraguensis and maize grown
      in aerated or stagnant deoxygenated nutrient solution were studied. Growth of
      maize was more adversely affected by low oxygen in the root zone (waterlogged
      soil or stagnant deoxygenated nutrient solution) compared with Z. nicaraguensis.
      In stagnant deoxygenated solution, Z. nicaraguensis was superior to maize in
      transporting oxygen from shoot base to root tip due to formation of larger
      aerenchyma and a stronger barrier to ROL in adventitious roots. The relationships
      between the ROL barrier formation and suberin and lignin depositions in roots are
      discussed. The ROL barrier, in addition to aerenchyma, would contribute to the
      waterlogging tolerance of Z. nicaraguensis.

PMID- 22471698
TI  - The Top 10 fungal pathogens in molecular plant pathology.
AB  - The aim of this review was to survey all fungal pathologists with an association
      with the journal Molecular Plant Pathology and ask them to nominate which fungal
      pathogens they would place in a 'Top 10' based on scientific/economic importance.
      The survey generated 495 votes from the international community, and resulted in
      the generation of a Top 10 fungal plant pathogen list for Molecular Plant
      Pathology. The Top 10 list includes, in rank order, (1) Magnaporthe oryzae; (2)
      Botrytis cinerea; (3) Puccinia spp.; (4) Fusarium graminearum; (5) Fusarium
      oxysporum; (6) Blumeria graminis; (7) Mycosphaerella graminicola; (8)
      Colletotrichum spp.; (9) Ustilago maydis; (10) Melampsora lini, with honourable
      mentions for fungi just missing out on the Top 10, including Phakopsora
      pachyrhizi and Rhizoctonia solani. This article presents a short resume of each
      fungus in the Top 10 list and its importance, with the intent of initiating
      discussion and debate amongst the plant mycology community, as well as laying
      down a bench-mark. It will be interesting to see in future years how perceptions
      change and what fungi will comprise any future Top 10.

PMID- 22471699
TI  - Systemic immunologic and inflammatory response after laparoscopic versus open
      nephrectomy: a prospective cohort trial.
AB  - PURPOSE: To compare the dynamics of systemic inflammatory indices during
      laparoscopic nephrectomy (LN) and standard open donor nephrectomy. PATIENTS AND
      METHODS: Participants in this cohort study were 54 adults without a history of
      renal surgery and no evidence of urinary tract infection who underwent
      transperitoneal LN (n=29) and open donor nephrectomy (n=25, control group). We
      recorded demographic characteristics, intraoperative parameters, and changes 24
      hours postoperatively in systemic inflammatory and immunologic values (body
      temperature, concentrations of white blood cell count [WBC], C-reactive protein
      [CRP], interleukin [IL]-6, and tumor necrosis factor [TNF]-alpha), and compared
      the mean changes between groups. RESULTS: Mean age was older in the LN group
      (45.6 vs 30.9 years; P<0.0001), and mean operative time was significantly shorter
      (83.1 min vs 101.6 min; P=0.004). Mean postoperative increase in IL-6 and body
      temperature in LN was significantly less than in control: For IL-6, 15.87 vs
      29.09 pg/mL, P=0.03; for body temperature, +0.22 degrees C vs +0.71 degrees C,
      P=0.001). Mean postoperative increases in levels of other inflammatory markers
      (CRP, TNF-alpha, WBC) did not differ significantly. No statistical correlation
      was found between operative time and changes in IL-6, CRP, TNF-alpha, WBC, or
      body temperature. CONCLUSION: Based on the smaller increase in serum IL-6 as the
      most important indicator of surgical stress, the surgical trauma-induced immune
      dysfunction may be less intense after LN than open surgery. This may explain the
      smooth convalescence after LN.

PMID- 22471700
TI  - Theoretical study of bond distances and dissociation energies of actinide oxides
      AnO and AnO2.
AB  - In the present study we evaluated trends in the bond distances and dissociation
      enthalpies of actinide oxides AnO and AnO(2) (An = Th-Lr) on the basis of
      consistent computed data obtained by using density functional theory in
      conjunction with relativistic small-core pseudopotentials. Computations were
      carried out on AnO (An = Th-Lr) and AnO(2) (An = Np, Pu, Bk-Lr) species, while
      for the remaining AnO(2) species recent literature data (Theor. Chem. Acc. 2011,
      129, 657) were utilized. The most important computed properties include the
      geometries, vibrational frequencies, dissociation enthalpies, and several excited
      electronic states. These molecular properties of the late actinide oxides (An =
      Bk-No) are reported here for the first time. We present detailed analyses of the
      bond distances, covalent bonding properties, and dissociation enthalpies.

PMID- 22471701
TI  - Timing of breeding carries over to influence migratory departure in a songbird:
      an automated radiotracking study.
AB  - 1. Determining how events interact across stages of the annual cycle is critical
      for understanding the factors that affect individual fitness. However, there is
      currently little information detailing how breeding events influence migratory
      behaviour. 2. Using an automated digital telemetry array and an isolated island
      breeding population of Savannah sparrows Passerculus sandwichensis, we provide
      the first direct evidence that the timing of breeding events carries over to
      influence the timing of migration in a songbird and assess for the first time how
      weather conditions on the breeding grounds also affect departure dates. 3. Date
      of migratory departure between September and October was strongly influenced by
      date of breeding completion in adults and fledging date in juveniles from June to
      July. 4. With respect to weather, adults departed during the first half of high
      pressure systems, while juveniles departed throughout the entirety of high
      pressure systems (including rainy evenings on the western edge of systems). 5. By
      combining both ecological and weather data, we could explain almost all variation
      in departure date for adults (95%), but weather conditions were not a good
      predictor of departure date for juveniles. 6. Our results provide strong evidence
      that the timing of breeding events is an important driver of migration timing and
      that exact departure dates are fine-tuned according to local weather conditions
      in adults, but not in juveniles.

PMID- 22471702
TI  - Deficiency of interleukin-1 receptor antagonist responsive to anakinra.
AB  - We describe a 3-month-old infant who presented to our institution with
      interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of
      neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis,
      and persistently high acute-phase reactants. Skin findings promptly improved upon
      initiation of treatment with anakinra (recombinant human IL-1 receptor
      antagonist), and the bony lesions and systemic inflammation resolved with
      continued therapy. 

PMID- 22471704
TI  - Anaplastic lymphoma kinase in human cancer.
AB  - The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is now implicated
      in a wide range of human cancers. Results from recent clinical trials with ALK
      inhibitors provide promise for patients harboring oncogenic ALK lesions. This
      review will discuss our current understanding of ALK in human cancer and the
      implication of recent results for treatment.

PMID- 22471703
TI  - The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus
      replication through interferon gamma-inducible protein-10.
AB  - BACKGROUND: Co-infection with human immunodeficiency virus-1 (HIV-1) and
      hepatitis C virus (HCV) is associated with faster progression of liver disease
      and an increase in HCV persistence. However, the mechanism by which HIV-1
      accelerates the progression of HCV liver disease remains unknown. RESULTS: HIV
      1/HCV co-infection is associated with increased expression of interferon gamma
      induced protein-10 (IP-10) mRNA in peripheral blood mononuclear cells (PBMCs).
      HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than
      in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV
      replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production.
      In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10
      monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV
      replication depends on IP-10. Taken together, these results suggest that HIV-1
      Tat protein activates HCV replication by upregulating IP-10 production.
      CONCLUSIONS: HIV-1/HCV co-infection is associated with increased expression of IP
      10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10
      activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP
      10 production. These results expand our understanding of HIV-1 in HCV replication
      and the mechanism involved in the regulation of HCV replication mediated by HIV-1
      during co-infection.

PMID- 22471705
TI  - Src kinase inhibitors: promising cancer therapeutics?
AB  - Src is the cellular counterpart of the first identified viral oncogene v-Src. It
      forms part of a large family of nonreceptor tyrosine kinases that have been
      extensively studied over the last few decades. This has led to the realization
      that Src can regulate a number of signaling pathways that impact on the behavior
      of tumor cells, including proliferation, survival, migration, invasion, and
      angiogenesis. There are currently four Src inhibitors (dasatinib, saracatinib,
      bosutinib, and KX01) in clinical development, and although there is a plethora of
      information on their activity in preclinical models their clinical efficacy has
      been disappointing. Here we review the current status of the Src inhibitors and
      highlight the difficulties involved in assessing these therapeutics in the
      clinical setting. In the future it will be important to combine our knowledge of
      basic Src biology with the use of appropriate preclinical models to aid the
      design of clinical trials. Taking this integrated approach will hopefully help to
      realize the true potential of Src kinase inhibitors.

PMID- 22471707
TI  - Inhibitors of cell cycle kinases: recent advances and future prospects as cancer
      therapeutics.
AB  - The cell cycle is a tightly regulated series of events that governs cell
      replication and division. Deregulation of cell cycle kinases, e.g., cyclin
      dependent kinases (CDKs), can initiate a hyper-proliferative cell phenotype and
      cause genomic instability, thus facilitating malignant transformation.
      Pharmacological agents targeting CDKs have been developed as potential anti
      cancer agents for over 20 years, evolving from early pan-CDK inhibitors to second
      generation inhibitors with much greater specificity and selectivity. Despite
      these advances in drug design and highly successful preclinical investigations,
      CDK inhibitors have yet to achieve their expected efficacy in clinical trials. In
      addition, inhibitors of other cell cycle kinases are currently progressing
      through clinical trials. Recent biochemical and genetic studies might be used to
      improve the effectiveness of cell cycle kinase inhibitors as anti-cancer agents
      through better drug design, therapeutic combinations, and patient selection.

PMID- 22471708
TI  - FLT3 signaling and the development of inhibitors that target FLT3 kinase
      activity.
AB  - The FMS-like receptor tyrosine kinase-3 (FLT3) plays a key role in hematopoietic
      development and is frequently mutated in patients with acute myeloid leukemia
      (AML). These mutations render FLT3 constitutively active, and patients harboring
      these mutations have a poor prognosis. Targeting the kinase activity of FLT3 with
      inhibitory compounds is therefore an attractive therapeutic option. Over the last
      few years, numerous FLT3 inhibitors have undergone clinical trials. Although some
      have been disappointing, some newer agents have shown promise. This review
      provides an overview of FLT3 signaling, recent progress with next-generation
      inhibitors, and unexpected hurdles encountered when combining FLT3 inhibitors
      with chemotherapy.

PMID- 22471706
TI  - Targeting the insulin-like growth factor receptor: developing biomarkers from
      gene expression profiling.
AB  - Overwhelming evidence implicates insulin-like growth factor (IGF) signaling in
      the growth and survival of many types of human cancer cells. Numerous inhibitors
      of the IGF1 receptor (IGF1R) have been developed, and they displayed remarkable
      antineoplastic activity in preclinical models and promising success in early
      phase clinical trials. However, while responses have been observed in numerous
      cancer types, they have occurred in a minority of patients, and serious
      toxicities have been observed. Identifying patients likely to benefit from anti
      IGF1R therapy requires further characterizing the role of IGF1 signaling in
      various stages of tumorigenesis in order to identify critical downstream factors
      that may be used as predictors of response, or to serve as novel therapeutic
      targets. Recent microarray analyses have begun to unravel expression "signatures"
      specific for IGF1 that correlate with poor breast cancer prognosis and with
      response to anti-IGFIR inhibitors. In this review we briefly discuss the history
      of the IGF1 family in neoplasia, how it is targeted, results from clinical
      trials, and the quest for biomarkers that will predict response to IGF1R-targeted
      therapy.

PMID- 22471709
TI  - Targeting of EPH receptor tyrosine kinases for anticancer therapy.
AB  - Intense research over the past 15 years has demonstrated Eph receptors and their
      cell surface ephrin ligands to be one of the most prevalent and complex cell-cell
      communication systems; this system guides cell positioning and orchestrates
      tissue patterning in multicellular organisms by coordinating synchronised cell
      cell adhesion or segregation of interacting cells. The expression of many Eph and
      ephrin family members together with their embryonic patterning functions often re
      emerge during oncogenesis and have generated considerable interest as targets for
      anticancer therapies. The first generation of monoclonal antibodies, kinase
      inhibitors, and vaccines suggests considerable promise in preclinical and early
      clinical development, but there is little doubt that successful clinical use will
      rely on a comprehensive understanding of the complex and sometimes puzzling
      activities of Eph receptors during tumor progression.

PMID- 22471710
TI  - Targeting the human kinome for cancer therapy: current perspectives.
AB  - As highlighted by other articles in this review issue, great progress has been
      made in the development of targeted treatment modalities directed against
      particular oncogenic kinases, and the translation of these therapies into the
      clinic. However, recent data from cancer genome sequencing projects indicate that
      the spectrum of kinases that contribute to cancer progression is wider than
      previously imagined, and as international projects in this area gather momentum,
      it appears likely that further kinase oncogenes will be identified, and the roles
      of previously characterized ones will be extended to subsets of additional
      cancers. In addition, complementary approaches such as functional genomics and
      mass spectrometry (MS)-based proteomics are providing important insights into the
      functional roles played by specific kinases in particular cancers, the dependency
      of these roles on genetic background, how altered kinase regulation perturbs
      intracellular signaling networks, and how the latter respond to targeted agents
      that target the kinase in question. While other articles in this issue focus on
      individual cancer-associated kinases and their therapeutic targeting, the aim of
      this review is to take a broader perspective regarding our current knowledge of
      the cancer kinome and how this can be expanded and exploited for clinical
      utility.

PMID- 22471711
TI  - Association between physical activity and academic performance in Korean
      adolescent students.
AB  - BACKGROUND: Recently, physical activity (PA) was found to improve cognitive and
      memory functions in the brain; however, no epidemiological studies have
      specifically investigated this phenomenon in the Korean adolescent student
      population. The purpose of this study was to investigate the effects of various
      types of PA undertaken at various frequencies, on the academic performance of
      Korean adolescent students. METHODS: A total of 75,066 adolescent students
      (39,612 males and 35,454 females) from the 7th to the 12th grades took part in
      the 5th Korea Youth Risk Behavior Web-based Survey (KYRBWS-V) project, conducted
      in 2009. Using data acquired by that survey, potential relations between PA and
      academic performance were explored in this current study through multivariate
      logistic regression analysis incorporating adjustment for covariate variables
      including age, body mass index, the parents' education level, and the income
      status of the family. RESULTS: Compared with boys who did not regularly
      participate in any vigorous PA, those who did so 2, 3, or 4 times a week had
      greater odds of reporting an average or above-average academic performance.
      Compared with boys who did not participate in any moderate PA, those who did so
      1, 2, 3, 4, or >=5 times a week also had greater odds of reporting an average or
      above-average academic performance. Interestingly, when compared with boys who
      did not participate in any strengthening exercises, those undertaking
      strengthening exercises >=5 times a week had lesser odds of reporting a below
      average academic performance. Compared with girls who did not regularly
      participate in any vigorous PA, those who did so >=5 times a week had greater
      odds of reporting an average or above-average academic performance. Compared with
      girls who did not participate in any moderate PA, those that did so 2 or 3 times
      a week had greater odds of reporting an average or above-average academic
      performance. Interestingly, when compared with girls who did not regularly
      participate in any strengthening exercises, those undertaking strengthening
      exercises >=5 times a week had lesser odds of reporting a below-average academic
      performance. CONCLUSIONS: Our analyses of the relevant data from the KYRBWS-V
      suggested that vigorous PA was positively correlated with academic performance in
      the case of boys, and moderate PA was positively correlated with academic
      performance in both boys and girls. However, strengthening exercises were not
      positively correlated with academic performance in boys or girls. Furthermore,
      when undertaken 5 or more times a week, vigorous PA in boys and strengthening
      exercises in both boys and girls were negatively correlated with academic
      performance. The results from this study are potentially relevant to the
      development of future education policies in Korean schools, particularly with
      regard to early intervention strategies designed to identify and counteract
      potential factors contributing to academic underachievement.

PMID- 22471712
TI  - Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal
      axis in women with irritable bowel syndrome.
AB  - BACKGROUND: Evidence suggests that subgroups of patients with irritable bowel
      syndrome (IBS) are hyper-responsive to a variety of laboratory stress conditions.
      METHODS: This study compared sleep quality and night time plasma
      adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to
      anticipation of public speaking between 43 women with IBS and 24 healthy control
      women. In addition, comparisons were made between subgroups within the IBS sample
      based on predominant stool patterns, 22 IBS-constipation and 21 IBS-diarrhea.
      Subjects slept three nights in a sleep laboratory, and on the third night serial
      blood samples were drawn every 20 min from 08:00 PM until awakening. As the
      subjects had different sleep onsets, each subject's results were synchronized to
      the first onset of stage 2 sleep. KEY RESULTS: Compared the healthy control
      group, women with IBS had significantly worse sleep efficiency, and higher
      cortisol but not ACTH levels over the night. However, there were no IBS bowel
      pattern subgroup differences. Among IBS subjects, cortisol levels early in the
      night were higher than found in our previous study with a similar protocol but
      without the threat of public speaking. These results suggest that a social
      stressor, such as public speaking prior to bedtime, increases cortisol but not
      ACTH levels suggesting HPA dysregulation in women with IBS. CONCLUSIONS &
      INFERENCES: This response to a social stressor contributes to our understanding
      of the relationship of stress to symptom expression in IBS.

PMID- 22471713
TI  - Isoflurane causes neocortical but not hippocampal-dependent memory impairment in
      mice.
AB  - BACKGROUND: The aim of this study is to investigate the effect of general
      anaesthesia induced by isoflurane with buprenorphine on hippocampus-dependent and
      neocortex-dependent memory, respectively, in mice, and in addition, to compare
      the effects of such anaesthesia on these memory processes with the effects
      induced by lipopolysaccharide (LPS) administration on the same memory processes.
      METHODS: To assess hippocampus-dependent memory, isoflurane (for 15 min) after
      buprenorphine injection, or LPS 100 MUg/kg (intraperitoneally) was administered
      24 h before or after fear conditioning. The effect of these treatments on
      hippocampus-dependent memory was assessed using contextual fear-conditioning
      tasks at day 4. To assess neocortex-dependent memory, isoflurane anaesthesia or
      LPS was given 72 h after contextual fear conditioning. Neocortex-dependent memory
      assessment was performed at day 32. RESULTS: Unlike LPS injection, isoflurane
      with buprenorphine-induced anaesthesia does not impair freezing responses in
      hippocampus-dependent fear-conditioning memory tasks. On anterograde amnesia
      assessment: 49.67 +/- 6.87% for the anaesthesia group and 54.5 +/- 4.12% for the
      control group. On retrograde amnesia assessment: 47.16 +/- 8.71% for the
      anaesthesia group and 54.5 +/- 4.12% for control group; P > 0.05. Thus, neither
      isoflurane nor buprenorphine impair hippocampus-dependent memory. However, on the
      neocortex-dependent memory task, both isoflurane-induced anaesthesia and LPS
      induced inflammation result in reduced freezing responses: 62.13 +/- 5.80% for
      the anaesthesia group, 74.63 +/- 5.69% for the LPS group, and 81.75 +/- 3.26% for
      the control group; P < 0.05 compared with control group. CONCLUSION: General
      anaesthesia induced by isoflurane with buprenorphine may result in impairment of
      neocortex-dependent memory in mouse. However, general anaesthesia so induced does
      not impair hippocampus-dependent memory in mouse in our experimental conditions.

PMID- 22471714
TI  - Learning about oneself through others: experiences of a group-based patient
      education programme about irritable bowel syndrome.
AB  - BACKGROUND: People with irritable bowel syndrome (IBS) often experience severe
      illness-related troubles in their everyday lives. Many persons also perceive
      their disease-related knowledge to be insufficient, and they feel dissatisfied
      with their inability to improve well-being. Previous research about patient
      education and IBS has emphasized biomedical outcomes of symptoms, health
      promoting behaviours, coping and health-related quality of life, rather than
      people's experiences. AIM: To explore people's experiences of participating in a
      multidisciplinary group-based patient education programme about IBS and of the
      influence of this programme on everyday life with illness. METHODS: Focus group
      interviews were performed with 31 persons after their participation in the
      patient education programme. Interpretive description guided the inductive
      analysis of data. The study was approved by the local research ethics committee.
      FINDINGS: The analysis revealed four patterns; being part of a safe community,
      learning about oneself through others, understanding and controlling the body and
      illness as a whole, and being outside of the community. The pattern of learning
      about oneself through others can be described as a reciprocal activity of
      learning by listening to, telling and observing others. Being among similar
      others had created feelings among most of the focus group participants of being
      part of a safe community where taboo subjects related to IBS-symptoms could be
      outspoken. Understanding the body and illness as a whole had enhanced their
      ability to interpret bodily signals and to handle trouble some situations with
      greater self-confidence, and this regained their access to the social everyday
      world. CONCLUSION: The combination of reciprocal sharing of experiences and the
      provision of professional scientific knowledge during the patient education
      programme together contributed to a growing readiness to improve well-being in
      everyday life, for most of the participating individuals. This was based on new
      understandings of the body and illness as a whole and of new abilities to make
      knowledge-based decisions about what strategies to use in overcoming illness
      related troubles.

PMID- 22471715
TI  - Dermal toxicity of ZnO nanoparticles: a worrying feature of sunscreen?

PMID- 22471716
TI  - Nanomedicine against multidrug resistance in cancer treatment.

PMID- 22471719
TI  - In vitro targeted imaging and delivery of camptothecin using cetuximab-conjugated
      multifunctional PLGA-ZnS nanoparticles.
AB  - BACKGROUND: Targeted cancer therapy has been extensively developed to improve the
      quality of treatment by reducing the systemic exposure of cytotoxic drug.
      Polymeric nanoparticles with conjugated targeting agents are widely investigated
      because they offer tunability in particle size, drug release profile and
      biocompatibility. MATERIALS & METHODS: Here, we have prepared targeted
      multifunctional nanoparticles composed of a poly(lactic-co-glycolic acid) matrix,
      ZnS:Mn(2+) quantum dots and camptothecin, and targeted them to EGF receptor
      overexpressing cells with a cetuximab antibody. RESULTS: Physicochemical
      characterization of multifunctional nanoparticles showed stable particles with
      sizes of <200 nm. In vitro drug release and blood contact studies showed a
      sustained release profile, with limited hemolysis. In vitro cytotoxicity and cell
      uptake studies were carried out in A549, KB and MFC-7 cell lines using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, FACS, fluorescent
      microscopic images and spectroflourimetry. CONCLUSION: Our studies revealed
      higher camptothecin activity and uptake in cell lines that overexpress the EGF
      receptor. All these results suggest that anti-EGF receptor cetuximab-conjugated
      poly(lactic-co-glycolic acid) multifunctional nanoparticles can be used as a
      potential nanomedicine against cancer.

PMID- 22471720
TI  - Understanding nonviral nucleic acid delivery with quantum dot-FRET nanosensors.
AB  - Nonviral delivery of nucleic acids is a potentially safe and viable therapeutic
      modality for inherited and acquired diseases. However, current systems have
      proven too inefficient for widespread clinical translation. The rational design
      of improved carriers depends on a quantitative, mechanistic understanding of the
      rate-limiting barriers to efficient intracellular delivery. Separation of the
      nucleic acid from the carrier is one of the barriers, which may be analyzed by
      Forster resonance energy transfer (FRET), a mechanism used to detect interactions
      between fluorescently labeled molecules. When applied to the molecular components
      of polymer or lipid-based nanocomplexes, FRET provides information on their
      complexation status, uptake, release and degradation. Recently, the design of
      FRET systems incorporating quantum dots as energy donors has led to improved
      signal stability, allowing prolonged measurements, as well as increased
      sensitivity, enabling direct detection and the potential for multiplexing. The
      union of quantum dots and FRET is providing new insights into the mechanisms of
      nonviral nucleic acid delivery through convergent characterization of delivery
      barriers, and has the potential to accelerate the design of improved carriers to
      realize the potential of nucleic acid therapeutics and gene medicine.

PMID- 22471721
TI  - Nanoparticles and spermatogenesis: how do nanoparticles affect spermatogenesis
      and penetrate the blood-testis barrier.
AB  - Due to the widespread use of nanomaterials in medical, industrial and military
      applications, the question as to whether nanoparticles (NPs) cause harmful
      disturbances in human health, especially on the reproductive system, remains a
      matter of concern. In this review, we focus mainly on the in vivo and in vitro
      effects of NPs on spermatogenesis at the clinical, cellular and molecular levels.
      In general, most NPs display adverse effects on spermatogenesis at these various
      levels; but, some NPs show no adverse effects. However, the mechanism underlying
      NP disruption of spermatogenesis and penetration of the blood-testis barrier
      remains unclear. In this review, we raise many hypotheses for experimental
      testing in order to elucidate the mechanism.

PMID- 22471722
TI  - Cancer stem cells and drug resistance: the potential of nanomedicine.
AB  - Properties of the small group of cancer cells called tumor-initiating or cancer
      stem cells (CSCs) involved in drug resistance, metastasis and relapse of cancers
      can significantly affect tumor therapy. Importantly, tumor drug resistance seems
      to be closely related to many intrinsic or acquired properties of CSCs, such as
      quiescence, specific morphology, DNA repair ability and overexpression of
      antiapoptotic proteins, drug efflux transporters and detoxifying enzymes. The
      specific microenvironment (niche) and hypoxic stability provide additional
      protection against anticancer therapy for CSCs. Thus, CSC-focused therapy is
      destined to form the core of any effective anticancer strategy. Nanomedicine has
      great potential in the development of CSC-targeting drugs, controlled drug
      delivery and release, and the design of novel gene-specific drugs and diagnostic
      modalities. This review is focused on tumor drug resistance-related properties of
      CSCs and describes current nanomedicine approaches, which could form the basis of
      novel combination therapies for eliminating metastatic and CSCs.

PMID- 22471725
TI  - Addressing smoking and other health risk behaviours using a novel telephone
      delivered intervention for homeless people: a proof-of-concept study.
AB  - INTRODUCTION AND AIMS: Despite substantial health disadvantage, few intervention
      studies have examined ways to deliver smoking cessation support to homeless
      people. This proof-of-concept study explored the feasibility and acceptability of
      a novel, low-cost, telephone-delivered program. DESIGN AND METHODS: Clients aged
      over 18 years, English-speaking and currently receiving accommodation support
      from a homelessness outreach centre were invited to participate in a 'Phone for
      Health' program. Six sessions conducted once per week provided participants with
      personalised counselling about smoking cessation or reduction, as well as fruit
      and vegetable consumption, alcohol use, physical activity and sun protection.
      Both clients and staff completed follow-up quantitative surveys, and clients
      completed qualitative interviews. RESULTS: Of 14 eligible participants, 12
      consented to taking part and completed baseline measures, 10 commenced the
      telephone intervention and six completed the intervention program. Average length
      of telephone sessions was 17.8 min and participants completed an average of 3.8
      sessions. Findings suggested high acceptability with most participants reporting
      that the Phone for Health program helped them meet their smoking reduction goals,
      and was convenient, useful and practical. Most participants reported making
      changes to their health risk behaviours as a result of taking part in the
      program. DISCUSSION AND CONCLUSIONS: Telephone delivery of the smoking cessation
      and other health behaviours intervention was acceptable and feasible. The results
      provide pragmatic lessons for the development of future health research and
      practice with an underserved population markedly difficult to reach and engage.

PMID- 22471726
TI  - Reliability and validity of the ultrasound technique to measure the rectus
      femoris muscle diameter in older CAD-patients.
AB  - BACKGROUND: The increasing age of coronary artery disease (CAD) patients and the
      occurrence of sarcopenia in the elderly population accompanied by 'fear of
      moving' and hospitalization in these patients often results in a substantial loss
      of skeletal muscle mass and muscle strength. Cardiac rehabilitation can improve
      exercise tolerance and muscle strength in CAD patients but less data describe
      eventual morphological muscular changes possibly by more difficult access to
      imaging techniques. Therefore the aim of this study is to assess and quantify the
      reliability and validity of an easy applicable method, the ultrasound (US)
      technique, to measure the diameter of rectus femoris muscle in comparison to the
      muscle dimensions measured with CT scans. METHODS: 45 older CAD patients without
      cardiac event during the last 9 months were included in this study. 25 patients
      were tested twice with ultrasound with a two day interval to assess test-retest
      reliability and 20 patients were tested twice (once with US and once with CT) on
      the same day to assess the validity of the US technique compared to CT as the
      gold standard. Isometric and isokinetic muscle testing was performed to test
      potential zero-order correlations between muscle diameter, muscle volume and
      muscle force. RESULTS: An intraclass correlation coefficient (ICC) of 0.97
      ((95%CL: 0.92 - 0.99) was found for the test-retest reliability of US and the ICC
      computed between US and CT was 0.92 (95%CL: 0.81 - 0.97). The absolute difference
      between both techniques was 0.01 +/- 0.12 cm (p = 0.66) resulting in a typical
      percentage error of 4.4%. Significant zero-order correlations were found between
      local muscle volume and muscle diameter assessed with CT (r = 0.67, p = 0.001)
      and assessed with US (r = 0.49, p < 0.05). Muscle strength parameters were also
      significantly correlated with muscle diameter assessed with both techniques
      (range r = 0.45-r = 0.61, p < 0.05). CONCLUSIONS: Ultrasound imaging can be used
      as a valid and reliable measurement tool to assess the rectus femoris muscle
      diameter in older CAD patients.

PMID- 22471727
TI  - Unrepaired tetralogy of fallot in an 85-year-old man.
AB  - Tetralogy of Fallot is the most common cyanotic congenital heart defect and
      accounts for about 5% of all congenital cardiopathies. The definitive treatment
      modality for tetralogy of Fallot is reparative surgery, which is recommended to
      be performed by the time of diagnosis. Without surgical repair, most patients
      would die during their childhood. In the past, survival data indicated that 66%
      of persons with tetralogy of Fallot not surgically treated lived until the age of
      1, 49% lived until the age of 3, and 24% lived until the age of 10. We now
      present a rare case of a man with unrepaired tetralogy of Fallot who survived
      until the age of 85. He presented to our emergency room for dyspnea and
      palpitations due to a new-onset high-frequency atrial fibrillation and acute
      heart failure; transthoracic echocardiography showed the presence of tetralogy of
      Fallot. By consulting the scientific literature, we can say that this is the
      second patient who survived more than 80 years without surgical intervention.

PMID- 22471728
TI  - The impact of sirolimus on sex hormones in male adolescent kidney recipients.

PMID- 22471729
TI  - Crystal structural, magnetic, and transport properties of layered cobalt
      oxyfluorides, Sr2CoO(3+x)F(1-x) (0 <= x <= 0.15).
AB  - The crystal structure of the layered cobalt oxyfluoride Sr(2)CoO(3)F synthesized
      under high-pressure and high-temperature conditions has been determined from
      neutron powder diffraction and synchrotron powder diffraction data collected at
      temperatures ranging from 320 to 3 K. This material adopts the tetragonal space
      group I4/mmm over the measured temperature range and the crystal structure is
      analogous to n = 1 Ruddlesden-Popper type layered perovskite. In contrast to
      related oxyhalide compounds, the present material exhibits the unique
      coordination environment around the Co metal center: coexistence of square
      pyramidal coordination around Co and anion disorder between O and F at the apical
      sites. Magnetic susceptibility and electrical resistivity measurements reveal
      that Sr(2)CoO(3)F is an antiferromagnetic insulator with the Neel temperature
      T(N) = 323(2) K. The magnetic structure that has been determined by neutron
      diffraction adopts a G-type antiferromagnetic order with the propagation vector k
      = (1/2 1/2 0) with an ordered cobalt moment MU = 3.18(5) MU(B) at 3 K, consistent
      with the high spin electron configuration for the Co(3+) ions. The
      antiferromagnetic and electrically insulating states remain robust even against
      15%-O substation for F at the apical sites. However, applying pressure exhibits
      the onset of the metallic state, probably coming from change in the electronic
      state of square-pyramidal coordinated cobalt.

PMID- 22471730
TI  - Relevance of xenobiotic enzymes in human skin in vitro models to activate pro
      sensitizers.
AB  - Skin exposure to sensitizing chemicals can induce allergic reactions. Certain
      chemicals, so called pro-sensitizers, need metabolic activation to become
      allergenic. Their metabolic activation occurs in skin cells such as keratinocytes
      or dendritic cells. These cell types are also incorporated into dermal in vitro
      test systems used to assess the sensitizing potential of chemicals for humans. In
      vitrosystems range from single cell cultures to organotypic multi-cellular
      reconstructed skin models. Until now, their metabolic competence to unmask
      sensitizing potential of pro-sensitizers was rarely investigated. This review
      aims to summarize current information on available skin in vitro models and the
      relevance of xenobiotic metabolizing enzymes for the activation of pro
      sensitizers such as eugenol, 4-allylanisole, and ethylendiamine. Among others,
      these chemicals are discussed as performance standards to validate new coming in
      vitro systems for their potential to identify pro-sensitizers.

PMID- 22471731
TI  - Ordered array of gold semishells on TiO2 spheres: an ultrasensitive and
      recyclable SERS substrate.
AB  - Ordered array of Au semishells on TiO(2) spheres with controlled size are
      prepared by combining the nanosphere self-assembly and atomic layer deposition
      (ALD). This ordered 2-D structure with designed array of metal nanogaps can be
      used as an ultrasensitive surface-enhanced Raman scattering (SERS) substrate with
      high reproducibility and stability. More importantly, the SERS substrates are
      recyclable, as enabled by their self-cleaning function due to the TiO(2)
      photocatalytic degradation of the target molecules. The high SERS sensitivity and
      recyclability are demonstrated by the detection of Rhodamine 6G (R6G) and
      brilliant cresyl blue (BCB) molecules. As both the nanosphere lithography and ALD
      are scalable processes, such 2-D ordered substrates may find applications in
      chemical sensing.

PMID- 22471732
TI  - Structural assessment of the impact of environmental constraints on Arabidopsis
      thaliana leaf growth: a 3D approach.
AB  - Light and soil water content affect leaf surface area expansion through
      modifications in epidermal cell numbers and area, while effects on leaf thickness
      and mesophyll cell volumes are far less documented. Here, three-dimensional
      imaging was applied in a study of Arabidopsis thaliana leaf growth to determine
      leaf thickness and the cellular organization of mesophyll tissues under moderate
      soil water deficit and two cumulative light conditions. In contrast to surface
      area, thickness was highly conserved in response to water deficit under both low
      and high cumulative light regimes. Unlike epidermal and palisade mesophyll
      tissues, no reductions in cell number were observed in the spongy mesophyll;
      cells had rather changed in volume and shape. Furthermore, leaf features of a
      selection of genotypes affected in leaf functioning were analysed. The low-starch
      mutant pgm had very thick leaves because of unusually large palisade mesophyll
      cells, together with high levels of photosynthesis and stomatal conductance. By
      means of an open stomata mutant and a 9-cis-epoxycarotenoid dioxygenase
      overexpressor, it was shown that stomatal conductance does not necessarily have a
      major impact on leaf dimensions and cellular organization, pointing to additional
      mechanisms for the control of CO(2) diffusion under high and low stomatal
      conductance, respectively.

PMID- 22471733
TI  - Direct antiproliferative effect of nonsteroidal 17beta-hydroxysteroid
      dehydrogenase type 1 inhibitors in vitro.
AB  - Inhibition of the local formation of estrogens seems to be an attractive strategy
      for pharmacological intervention in hormone-dependent disorders. The direct
      antiproliferative properties of ten nonsteroidal 17beta-hydroxysteroid
      dehydrogenase type 1 (17beta-HSD1) inhibitors were investigated on human cancer
      cell lines of gynecological origin. The mechanism of the antiproliferative action
      was approximated by cell cycle analysis, fluorescent microscopy, BrdU assay,
      determination of caspase-3 activity and quantification of the expression of cell
      cycle regulators at mRNA level. Treatment of HeLa cells with some of the
      compounds resulted in a concentration-dependent inhibition of the G1-S transition
      and an increase in the apoptotic population. The most effective agents increased
      the expression of tumor suppressors p21 and p53, while CDK2 and Rb were down
      regulated. The reported anticancer actions of the tested compounds are
      independent of the 17beta-HSD1-inhibiting capacity. These results indicate that
      it is possible to combine direct antiproliferative activity and 17beta-HSD1
      inhibition resulting in novel agents with dual mode of action. 

PMID- 22471734
TI  - Rapid environmental degradation in a subarctic ecosystem influences resource use
      of a keystone avian herbivore.
AB  - 1. Environmental degradation can change resource use strategies of animals and
      thereby affect survival and fitness. Arctic herbivores may be especially
      susceptible to the effects of such environmental change because their rapid
      growth rates demand high-quality forage, which may be limited as environmental
      conditions deteriorate. We studied the consequences of a trophic cascade, driven
      by Lesser Snow Goose (Chen caerulescens caerulescens) overgrazing on the south
      west coast of Hudson Bay, Canada, which has caused tidal marsh (TM) degradation
      and the reduction in high-quality forage plants, on gosling growth and resource
      use. 2. We compared resource use and body size of goslings that inhabited tidal
      and freshwater marsh (FM) to determine how current foraging strategies influence
      growth and to test the hypothesis that during early growth goslings require and
      so consume high-quality TM plants, but that during later growth they may switch
      to foraging in lower-quality FM. 3. To investigate gosling resource use
      throughout growth, we measured once a week for 28 days the body size of goslings
      as well as stable isotope ratios (delta(34) S, delta(15) N and delta(13) C) in
      multiple tissues of goslings that were collected from both TM and nearby FM. We
      also measured the stable isotope ratios in forage plants sampled along transects
      and from gosling foreguts. We used an isotope-mixing model to determine the
      contribution of FM plants to gosling tissues. 4. Contrary to the proposed
      hypothesis, goslings inhabiting FM or TM primarily consumed FM plants during
      early growth. Furthermore, goslings that foraged extensively in FM had similar
      growth rates and grew to a similar size and body mass, as goslings that foraged
      in the degraded TM. However, goslings that currently inhabit freshwater or TM
      were significantly smaller than goslings that inhabited TM in the 1980s prior to
      habitat degradation. 5. Consequences of smaller overall body size include
      decreased survival and fecundity for arctic-nesting geese. The ability of
      phenotypically plastic responses to sustain persistence is limited by reaction
      norms and the extent of environmental change. Current research is assessing
      whether those limits have been reached in this system.

PMID- 22471735
TI  - What would menthol smokers do if menthol in cigarettes were banned? Behavioral
      intentions and simulated demand.
AB  - AIMS:   The US Food and Drug Administration must consider whether to ban the use
      of menthol in cigarettes. This study examines how current smokers might respond
      to such a ban on menthol cigarettes. DESIGN:   Convenience sample of adolescent
      and adult smokers recruited from an online survey panel. SETTING:   United
      States, 2010. PARTICIPANTS:   A total of 471 adolescent and adult current
      cigarette smokers. MEASUREMENTS:   Respondents were asked a series of questions
      about how they might react if menthol cigarettes were banned. In addition,
      participants completed a simulation purchase task to estimate the demand for
      menthol and non-menthol cigarettes across a range of prices. FINDINGS:   Overall,
      36.1% of respondents said they always (18.9%) or usually (17.2%) smoked menthol
      cigarettes. When asked how they might respond to a ban on menthol cigarettes, 35%
      of current menthol smokers said they would stop smoking, and 25% said they would
      'find a way to buy a menthol brand'. Those who reported they might quit tended to
      have greater current intentions to quit [odds ratio (OR) = 4.47], while those who
      reported that they might seek illicit menthol cigarettes were far less likely to
      report current intentions to quit (OR = 0.06). Estimates for demand elasticity
      for preferred cigarette type were similar for menthol (alpha = 0.0051) and non
      menthol (alpha = 0.0049) smokers. Demand elasticity and peak consumption were
      related to usual cigarette type and cigarettes smoked per day, but did not appear
      to differ by race, gender or age. CONCLUSIONS:   Preliminary evidence suggests
      that a significant minority of smokers of menthol cigarettes in the United States
      would try to stop smoking altogether if such cigarettes were banned.

PMID- 22471737
TI  - Ecthyma gangrenosum and neutropenia in a previously healthy child.
AB  - Ecthyma gangrenosum is the cutaneous manifestation of pseudomonas infection in
      patients with sepsis. A previously healthy 7-month-old girl who developed ecthyma
      gangrenosum without apparent inciting factors became neutropenic secondary to
      autoimmune neutropenia 2 months after initial presentation. She was treated with
      appropriate surgical and medical intervention and was discharged in stable
      condition only to die suddenly 2 days after discharge.

PMID- 22471736
TI  - Prevalence of collagen VII-specific autoantibodies in patients with autoimmune
      and inflammatory diseases.
AB  - BACKGROUND: Autoimmunity to collagen VII is typically associated with the skin
      blistering disease epidermolysis bullosa acquisita (EBA), but also occurs
      occasionally in patients with systemic lupus erythematosus or inflammatory bowel
      disease. The aim of our present study was to develop an accurate immunoassay for
      assessing the presence of autoantibodies against collagen VII in large cohorts of
      patients and healthy donors. METHODS: Based on in silico antigenic analysis and
      previous wetlab epitope mapping data, we designed a chimeric collagen VII
      construct containing all collagen VII epitopes with higher antigenicity. ELISA
      was performed with sera from patients with EBA (n = 50), Crohn's disease (CD, n =
      50), ulcerative colitis (UC, n = 50), bullous pemphigoid (BP, n = 76), and
      pemphigus vulgaris (PV, n = 42) and healthy donors (n = 245). RESULTS: By ELISA,
      the receiver operating characteristics analysis yielded an area under the curve
      of 0.98 (95% CI: 0.9638-1.005), allowing to set the cut-off at 0.32 OD at a
      calculated specificity of 98% and a sensitivity of 94%. Running the optimized
      test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%),
      2 CD (4%; 95% CI: 0%-9.43%), 8 UC (16%; 95% CI: 5.8%-26%), 2 BP (2.63%; 95% CI:
      0%-6.23%), and 4 PV (9.52%; 95% CI: 0%-18.4%) patients as well as from 4 (1.63%;
      95% CI: 0%-3.21%) healthy donors reacted with the chimeric protein. Further
      analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1,
      IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant
      autoantigen. CONCLUSIONS: Using a chimeric protein, we developed a new sensitive
      and specific ELISA to detect collagen specific antibodies. Our results show a low
      prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease,
      pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune
      response against collagen VII is dominated by IgG4 autoantibodies. The new
      immunoassay should prove a useful tool for clinical and translational research
      and should improve the routine diagnosis and disease monitoring in diseases
      associated with collagen VII-specific autoimmunity.

PMID- 22471738
TI  - Genetic aspects of adrenocortical tumours and hyperplasias.
AB  - Adrenocortical tumours (ACT), which include adenomas, carcinomas and adrenal
      hyperplasia, may be associated with genetic syndromes, such as Li-Fraumeni
      syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1,
      familial adenomatous polyposis and Carney complex. Genetic defects have been
      found to be responsible for the disease in most of these syndromes, allowing
      genetic counselling to affected patients and family members. Here, we summarize
      the clinical criteria of these hereditary syndromes and briefly describe the
      genetic alterations related to them. In addition, we discuss the involvement of
      various genetic defects in the development of sporadic adrenocortical tumours.

PMID- 22471739
TI  - Healing outcomes at implants installed in sites augmented with particulate
      autologous bone and xenografts. An experimental study in dogs.
AB  - AIM: To evaluate the integration of implants installed at the interface of
      pristine and grafted tissue augmented with particulate autologous bone or
      deproteinized bovine bone mineral (DBBM), concomitantly with a collagen membrane.
      MATERIAL AND METHODS: In 6 Labrador dogs, the distal root of (3)P(3) and (4)P(4)
      was endodontically treated and hemi-sected, and the mesial roots extracted
      concomitantly with the extraction of (2)P(2). The buccal bony walls were removed,
      and two box-shaped defects, one larger and one smaller, were created. After 3
      months, flaps were elevated, and the defects were filled with particulate
      autologous bone or DBBM in the right and left side of the mandible, respectively.
      Collagen membranes were used to cover the grafted areas. Three months later,
      flaps were elevated, and a customized device was used as surgical guide to
      prepare the recipient sites at the interface between grafts and pristine bone.
      One implant was installed in each of the four defects. After 3 months, biopsies
      were harvested and ground sections prepared for histological evaluation. RESULTS:
      The augmentation technique was effective at all sites and all the foreseen
      implants were installed. In the histological analysis, all implants were
      integrated in mature bone, at both the buccal and lingual aspects. The most
      coronal bone-to-implant contact and the top of the buccal bony crest were located
      at a similar distance between test and control implants. However, these distances
      were higher at the larger compared with the smaller defects. Especially in the
      large defect, residual particles of DBBM were found embedded into connective
      tissue and located outside the bony crest. CONCLUSIONS: Particulate autologous
      bone as well as DBBM particles used to augment horizontally the alveolar bony
      process allowed for the osseointegration of implants installed after 3 months of
      healing.

PMID- 22471740
TI  - The outcome of critical illness in decompensated alcoholic liver cirrhosis.
AB  - BACKGROUND: The mortality of patients suffering from acute decompensated liver
      disease treated in the intensive care unit (ICU) varies between 50% and 100%.
      Previously published data suggest that liver-specific score systems are less
      accurate compared with the ICU-specific scoring systems acute physiology and
      chronic health evaluation II (APACHE II) and simplified organ failure assessment
      (SOFA) in predicting outcome. We hypothesized that in a Scandinavian cohort of
      ICU patients, APACHE II, SOFA, and simplified acute physiology score (SAPS II)
      were superior to predict outcome compared with the Child-Pugh score. METHODS: A
      single-centre retrospective cohort analysis was conducted in a university
      affiliated ICU. Eighty-seven adult patients with decompensated liver alcoholic
      cirrhosis were admitted from January 2007 to January 2010. RESULTS: The patients
      were severely ill with median scores: SAPS II 60, SOFA (day 1) 11, APACHE II 31,
      and Child-Pugh 12. Receiver operating characteristic curves area under curve was
      0.79 for APACHE II, 0.83 for SAPS II, and 0.79 for SOFA (day 1) compared with
      0.59 for Child-Pugh. In patients only in need of mechanical ventilation, the 90
      day mortality was 76%. If respiratory failure was further complicated by shock
      treated with vasopressor agents, the 90-day mortality increased to 89%. Ninety
      day mortality for patients in need of mechanical ventilation, vasoactive
      medication, and renal replacement therapy because of acute kidney injury was 93%.
      CONCLUSION: APACHE II, SAPS II, and SOFA were better at predicting mortality than
      the Child-Pugh score. With three or more organ failures, the ICU mortality was >
      90%. APACHE II > 30, SAPS II > 60, and SOFA at day 1 > 12 were all associated
      with a mortality of > 90%. Referral criteria of patients suffering from
      decompensated alcoholic liver disease should be revised.

PMID- 22471741
TI  - Minimal residual disease detection defined as the malignant fraction of the total
      primitive stem cell compartment offers additional prognostic information in acute
      myeloid leukaemia.
AB  - INTRODUCTION: Immunophenotypic detection of minimal residual disease (MRD) in
      bone marrow (BM) of acute myeloid leukaemia (AML) patients is of high prognostic
      relevance. Standard MRD percentage is assessed as a percentage of total white
      blood cells (WBCs) and is therefore highly dependent on WBC count. Peripheral
      blood (PB) contains more than five times lower MRD percentages. Therefore, PB in
      BM aspirates cause dilution of the MRD cells, possibly leading to false-negative
      results for BM MRD. The latter is avoided when relating the fraction of malignant
      primitive cells, identified by aberrant marker expression [aberrant primitive
      cells (aPC)], to the total population of primitive cells. Such a fraction may in
      addition reflect an important biological parameter. METHODS: As this approach is
      thus independent of WBC count and the total size of the primitive compartment, we
      investigated the role of aPC fractions on overall and relapse-free survival (RFS)
      in 98 patients with AML under the age of 60. RESULTS: We show that this approach
      identifies MRD-negative (as defined by % of WBC) but aPC-positive (as defined by
      % of primitive cells) patients with poor outcome after both first and second
      induction cycle of chemotherapy. CONCLUSION: As a result, in cases with a
      primitive marker present, RFS is best predicted when combining standard MRD
      percentage with aPC fractions.

PMID- 22471742
TI  - Mutations in the potassium channel subunit KCNE1 are associated with early-onset
      familial atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia. The potassium
      current IKs is essential for cardiac repolarization. Gain-of-function mutations
      in KV7.1, the pore-forming alpha-subunit of the IKs channel, have been associated
      with AF. We hypothesized that early-onset lone AF is associated with mutations in
      the IKs channel regulatory subunit KCNE1. METHODS: In 209 unrelated early-onset
      lone AF patients (< 40 years) the entire coding sequence of KCNE1 was
      bidirectionally sequenced. We analyzed the identified KCNE1 mutants
      electrophysiologically in heterologous expression systems. RESULTS: Two non
      synonymous mutations G25V and G60D were found in KCNE1 that were not present in
      the control group (n = 432 alleles) and that have not previously been reported in
      any publicly available databases or in the exom variant server holding exom data
      from more than 10.000 alleles. Proband 1 (female, age 45, G25V) had onset of
      paroxysmal AF at the age of 39 years. Proband 2 (G60D) was diagnosed with lone AF
      at the age of 33 years. The patient has inherited the mutation from his mother,
      who also has AF. Both probands had no mutations in genes previously associated
      with AF. In heterologous expression systems, both mutants showed significant gain
      of-function for IKs both with respect to steady-state current levels, kinetic
      parameters, and heart rate-dependent modulation. CONCLUSIONS: Mutations in KV7.1
      leading to gain-of-function of IKs current have previously been described in lone
      AF, yet this is the first time a mutation in the beta-subunit KCNE1 is associated
      with the disease. This finding further supports the hypothesis that increased
      potassium current enhances AF susceptibility.

PMID- 22471744
TI  - Steric effects on uranyl complexation: synthetic, structural, and theoretical
      studies of carbamoyl pyrazole compounds of the uranyl(VI) ion.
AB  - New bifunctional pyrazole based ligands of the type [C(3)HR(2)N(2)CONR'] (where R
      = H or CH(3); R' = CH(3), C(2)H(5), or (i)C(3)H(7)) were prepared and
      characterized. The coordination chemistry of these ligands with uranyl nitrate
      and uranyl bis(dibenzoyl methanate) was studied with infrared (IR), (1)H NMR,
      electrospray-mass spectrometry (ES-MS), elemental analysis, and single crystal X
      ray diffraction methods. The structure of compound
      [UO(2)(NO(3))(2)(C(3)H(3)N(2)CON{C(2)H(5)}(2))] (2) shows that the uranium(VI)
      ion is surrounded by one nitrogen atom and seven oxygen atoms in a hexagonal
      bipyramidal geometry with the ligand acting as a bidentate chelating ligand and
      bonds through both the carbamoyl oxygen and pyrazolyl nitrogen atoms. In the
      structure of [UO(2)(NO(3))(2)(H(2)O)(2)(C(5)H(7)N(2)CON {C(2)H(5)}(2))(2)], (5)
      the pyrazole ligand acts as a second sphere ligand and hydrogen bonds to the
      water molecules through carbamoyl oxygen and pyrazolyl nitrogen atoms. The
      structure of [UO(2)(DBM)(2)C(3)H(3)N(2)CON{C(2)H(5)}(2)] (8) (where DBM =
      C(6)H(5)COCHCOC(6)H(5)) shows that the pyrazole ligand acts as a monodentate
      ligand and bonds through the carbamoyl oxygen to the uranyl group. The ES-MS
      spectra of 2 and 8 show that the ligand is similarly bonded to the metal ion in
      solution. Ab initio quantum chemical studies show that the steric effect plays
      the key role in complexation behavior.

PMID- 22471743
TI  - An investigation of factors associated with the health and well-being of HIV
      infected or HIV-affected older people in rural South Africa.
AB  - BACKGROUND: Despite the severe impact of HIV in sub-Saharan Africa, the health of
      older people aged 50+ is often overlooked owing to the dearth of data on the
      direct and indirect effects of HIV on older people's health status and well
      being. The aim of this study was to examine correlates of health and well-being
      of HIV-infected older people relative to HIV-affected people in rural South
      Africa, defined as participants with an HIV-infected or death of an adult child
      due to HIV-related cause. METHODS: Data were collected within the Africa Centre
      surveillance area using instruments adapted from the World Health Organization
      (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample
      of 422 people aged 50+ participated. We compared the health correlates of HIV
      infected to HIV-affected participants using ordered logistic regressions. Health
      status was measured using three instruments: disability index, quality of life
      and composite health score. RESULTS: Median age of the sample was 60 years (range
      50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and
      HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than
      men to be in good functional ability. Women's adjusted odds of being in good
      overall health state were similarly lower than men's; while income and household
      wealth status were stronger correlates of quality of life. HIV-infected
      participants reported better functional ability, quality of life and overall
      health state than HIV-affected participants. DISCUSSION AND CONCLUSIONS: The
      enhanced healthcare received as part of anti-retroviral treatment as well as the
      considerable resources devoted to HIV care appear to benefit the overall well
      being of HIV-infected older people; whereas similar resources have not been
      devoted to the general health needs of HIV uninfected older people. Given
      increasing numbers of older people, policy and programme interventions are
      urgently needed to holistically meet the health and well-being needs of older
      people beyond the HIV-related care system.

PMID- 22471745
TI  - Concentration levels of IL-10 and TNFalpha cytokines in patients with human
      papilloma virus (HPV) DNA+ and DNA- cervical lesions.
AB  - The present study was performed to assess the immune response in women with human
      papilloma virus (HPV) DNA+ and DNA- cervical lesions. Eighty women with cervical
      lesions (age range = 25-70 years) and 20 healthy individuals (control group) were
      enrolled in the study. Lesions were cytologically classified into four groups:
      ASC-US (20), CINI (30), CINII-III (16), and cervical carcinoma (14) prior to HPV
      DNA detection. Estimation of interleukin (IL)-10 and tumor necrosis factor (TNF)
      alpha levels in cervical secretions and serum of the studied patients was
      performed utilizing ELISA. PCR screening kits were used to detect HPV DNA in
      cervical smears obtained from the studied cases with the different lesions. IL-10
      levels in cervical secretions of HPV DNA+ were significantly greater than those
      from DNA- patients (i.e., 88.73 vs 24.00 pg/ml) and from controls (i.e., 88.73 vs
      8.27 pg/ml) and the levels were higher in DNA- patients than in controls (i.e.,
      24.00 vs 8.27 pg/ml). In comparison, serum IL-10 levels in these patients did not
      significantly differ from control values (i.e., 13.69 vs 12.16 vs 9.99 pg/ml,
      respectively). TNFalpha levels in cervical secretions of the HPV DNA+ and DNA-
      cases did not significantly differ from values for the controls (i.e., 12.18 vs
      9.90 vs 7.90 pg/ml, respectively). Serum TNFalpha of these patients also did not
      differ significantly from controls (i.e., 11.59 vs 11.90 vs 10.83 pg/ml,
      respectively). The detected levels of IL-10 in cervical secretions of patients
      with HPV DNA+ lesions was significantly higher than in their sera, while
      secretion TNFalpha levels were nominally greater than sera values. Lastly, higher
      levels of IL-10 were observed in secretions of 10-14 (71.4%) patients who had
      progressive cervical lesions (HSIL and cervical cancer stages) who were HPV DNA+
      than observed in 20 of 66 (30.0%) of DNA- patients with similar progressive
      lesions. In general, the higher levels of IL-10 than of TNFalpha suggested a
      potential down-modulation of tumor-specific immune responses to HPV-infected
      lesions. This phenomenon appears to provide a tumor 'progressive'
      microenvironment in these particular patients.

PMID- 22471746
TI  - Epidermal growth factor receptor mutations in synchronous recurrent lung cancer
      in an 82-year-old woman. A case story.

PMID- 22471747
TI  - Induction cisplatin-based chemotherapy and following radiotherapy in locally
      advanced basal cell carcinoma of the skin.

PMID- 22471749
TI  - Influence of periosteal coverage on the osteointegration and stability of dental
      implant distractors.
AB  - OBJECTIVES: Dental implant distractors (DID) are an efficacious means of
      simultaneously augmenting the vertical bony height together with the installation
      of dental implants. Little is known about their biomechanical properties and
      osteointegration ability in the free fibula flap, where the periosteum is
      invariably damaged during the multiple osteotomies required for contouring
      purposes. MATERIALS AND METHODS: Twenty-four DID devices inserted into the tibias
      of 12 goats were evenly divided into three groups - whole periosteum (WP), half
      periosteum (HP), no periosteum (NP). Following 10 days of distraction and a 12
      week consolidation period, the animals were euthanized to retrieve all 12 tibias.
      The bone-implant bonded percentage (BIBP) and removal torques (RTQ) of each
      fixture were determined and statistically compared across the various groups.
      RESULTS: A slight decrease in both BIBP and RTQ values was observed across the
      WP, HP, and NP groups, respectively, with statistically significant differences
      in the BIBP for the WP and NP groups only. CONCLUSION: We conclude that although
      an intact periosteum is ideal for the osteointegration of the DID fixture,
      adequate stability can still be achieved due to the sufficient anchorage accorded
      by the base screws in the apical cortex.

PMID- 22471748
TI  - Aryl hydrocarbon receptor ligand effects in RBL2H3 cells.
AB  - The aryl hydrocarbon receptor (AHR) mediates toxic effects of dioxin and
      xenobiotic metabolism. AHR has an emerging role in the immune system, but its
      physiological ligands and functional role in immunocytes remain poorly
      understood. Mast cells are immunocytes that are central to inflammatory responses
      and release a spectrum of pro-inflammatory mediators including histamine, mast
      cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. The
      aim was to investigate the AHR in model mast cells and examine how both putative
      and known AHR ligands, e.g., kynurenine, kynurenic acid (KA), Resveratrol,
      indolmycin, and violacein, affect mast cell activation and signaling. These
      ligands were tested on calcium signaling, degranulation, and gene expression. The
      data show that AHR is present in three model mast cell lines, and that various
      known and putative AHR ligands regulate gene expression of Cyp1a1, a gene down
      stream of AHR. Furthermore, it was found that calcium influxes and mast cell
      secretory responses were enhanced or suppressed after chronic treatment with AHR
      agonists or antagonists, and that AHR ligands modified RBL2H3 cell degranulation.
      AHR ligands can chronically change cytokine gene expression in activated mast
      cells, as exemplified by IL-6. The antagonist Resveratrol repressed expression of
      induced IL-6 gene expression. Although KA and kynurenine are both AHR agonists,
      these ligands behaved differently in regards to degranulation and IL-6
      expression, indicating that they may function outside of AHR pathways. These data
      suggest considerable complexity in RBL2H3 responses to AHR ligands, with
      implications for understanding of both dioxin pathology and the immunological
      effects of endogenous AHR ligands.

PMID- 22471750
TI  - Indacaterol: a new long-acting beta2-agonist in the management of chronic
      obstructive pulmonary disease.
AB  - INTRODUCTION: Bronchodilators represent the mainstay of symptomatic treatment for
      chronic obstructive pulmonary disease (COPD). The principal bronchodilator agents
      are beta(2)-agonists, anticholinergics and methylxanthines, used singly or in
      combination. Indacaterol is a novel long-acting beta(2)-agonist for maintenance
      bronchodilator treatment of airflow obstruction in patients with COPD, approved
      in December 2009 by the European Medicines Association, and recently by the US
      Food and Drug Administration. It is administered once daily and is delivered by
      means of a single-dose dry powder inhaler (SDDPI). In Europe, the recommended
      dose is 150 MUg and the maximum dose is 300 MUg, while in the US the recommended
      dose is 75 MUg. Indacaterol shows evidence of a rapid onset of bronchodilation,
      and its bronchodilatory duration is sustained. AREAS COVERED: Numerous clinical
      studies have assessed the therapeutic effects of indacaterol in various
      physiologic parameters, as well as symptoms, disease progression, exacerbation
      rates, quality of life, safety and tolerability. This review summarises published
      evidence regarding the efficacy, tolerability and safety of indacaterol in regard
      to lung function and symptoms of COPD patients. EXPERT OPINION: Indacaterol, the
      novel once-daily beta(2)-agonist, has rapid and sustained bronchodilatory effect,
      showing excellent efficacy, tolerability and safety, as shown by all clinical
      trials so far.

PMID- 22471751
TI  - Chronic kidney disease and use of dental services in a United States public
      healthcare system: a retrospective cohort study.
AB  - BACKGROUND: As several studies have shown an association between periodontal
      disease and chronic kidney disease (CKD), regular dental care may be an important
      strategy for reducing the burden of CKD. Access to dental care may be limited in
      the US public health system. METHODS: In this retrospective cohort study of 6,498
      adult patients with (n = 2,235) and without (n = 4,263) CKD and at least 12
      months of follow-up within the San Francisco Department of Public Health
      Community Health Network clinical databases, we examined the likelihood of having
      a dental visit within the observation period (2005-2010) using Cox proportional
      hazards models. To determine whether dental visits reflected a uniform approach
      to preventive service use in this setting, we similarly examined the likelihood
      of having an eye visit among those with diabetes, for whom regular retinopathy
      screening is recommended. We defined CKD status by average estimated glomerular
      filtration rate based on two or more creatinine measurements >= 3 months apart
      (no CKD, >= 60 ml/min/1.73 m2; CKD, < 60 ml/min/1.73 m2). RESULTS: Only 11.0% and
      17.4% of patients with and without CKD, respectively, had at least one dental
      visit. Those with CKD had a 25% lower likelihood of having a dental visit [HR =
      0.75, 95% CI (0.64-0.88)] than those without CKD after adjustment for
      confounders. Among the subgroup of patients with diabetes, 11.8% vs. 17.2% of
      those with and without CKD had a dental visit, while 58.8% vs. 57.8% had an eye
      visit. CONCLUSIONS: Dental visits, but not eye visits, in a US public healthcare
      setting are extremely low, particularly among patients with CKD. Given the
      emerging association between oral health and CKD, addressing factors that impede
      dental access may be important for reducing the disparate burden of CKD in this
      population.

PMID- 22471752
TI  - Serum testosterone levels in diabetic men with and without erectile dysfunction.
AB  - Diabetes mellitus is a common chronic disease, affecting 0.5-2% worldwide. The
      Massachusetts Male Aging Study reported that up to 75% of men with diabetes have
      a lifetime risk of developing ED. Type 2 diabetes is associated with low total
      serum testosterone (TT) identified in several cross-sectional studies and
      systemic analyses. There is a lack of consensus regarding what constitutes the
      lowest level of testosterone within the boundaries of normality. In this
      retrospective study, we sought to evaluate the effect of associated co
      morbidities on serum total testosterone (TT) level in men with type 2 diabetes
      DM, either with or without erectile dysfunction (ED). Three hundred and ninety
      one patients were evaluated for erectile function using an abridged, five-item
      version of the International Index of Erectile Function-5. Measurements of TT,
      fasting lipid profile, blood sugar and glycated haemoglobin (HbA1c) were
      conducted. Penile hemodynamics was assessed using intracavernosal injection and
      penile duplex study. Hypogonadism was found in 126 cases (33.2%), and normal TT
      was observed in 254 (66.8%). ED was detected in 119 cases in the hypogonadal
      group (94.4%) as compared to 155/254 (61.0%) in eugonadal group, P = 0.0001. TT
      was lower in diabetic men with ED as compared to those with normal erectile
      function (EF), 392.4 +/- 314.9 versus 524.3 +/- 140.2 ng dl(-1) , respectively, P
      < 0.0001. After exclusion of patients with hypertension and dyslipidaemia, 185
      men were evaluated, and there was no difference in the mean TT level among men
      with ED 490.6 +/- 498.2 ng dl(-1)  versus normal EF 540.6 +/- 133.4 ng dl(-1) 
      although, HbA1c remained lower in men with normal erectile function. Receiver
      operating characteristic (ROC) curve of TT in men without associated co
      morbidities showed that EF was compromised at TT = 403.5 ng dl(-1)  or less.
      Sensitivity of 63.3% and a specificity of 94.0% were detected. At this level, ED
      was found in 33/38 (86.8%) men with TT 403.5 ng dl(-1) , whereas ED was observed
      in 57/147 (38.8%) men with TT >= 403.5 ng dl(-1)  (P < 0.0001). We propose a cut
      off value of 403.5 ng dl(-1)  of TT blood levels as an indicator for initiation
      of testosterone replacement therapy in diabetic men with ED. Further prospective
      controlled trials are recommended.

PMID- 22471753
TI  - Allergic contact dermatitis to gamma-irradiated WEBCOL alcohol prep pads.
AB  - We report a case of allergic contact dermatitis to WEBCOL((r)) alcohol prep pads
      in a healthy 17-year-old girl who showed no reaction to the individual components
      of the prep pads upon provocative use testing. Although several case reports have
      described allergic contact dermatitis to isopropyl alcohol, there have been no
      reports of allergic contact dermatitis to alcohol prep pads sterilized with gamma
      irradiation, a common sterilization technique capable of producing volatile
      products in this type of alcohol prep pad. 

PMID- 22471754
TI  - Effect of pendant group structure on the hydrolytic stability of polyaspartamide
      polymers under physiological conditions.
AB  - We describe the synthesis of metal chelating polymers based on polyaspartamide
      and polyglutamide backbones as carriers for (111)In in radioimmunoconjugates.
      These polymers [PAsp(DTPA), PGlu(DTPA)] have a biotin end group and
      diethylenetriaminepentaacetic acid (DTPA) chelators attached to the primary
      amines of the diethylenetriamine (DET) pendant groups of biotin-poly{N'-[N-(2
      aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)] and of biotin-poly{N'-[N-(2
      aminoethyl)-2-aminoethyl]glutamide} [PGlu(DET)]. Like Asn-containing proteins and
      polypeptides, polyaspartamides undergo uncatalyzed degradation under model
      physiological conditions (10 mM phosphate buffer, pH 7.4, 150 mM NaCl). We
      studied the uncatalyzed degradation of the polyaspartamide polymers by size
      exclusion chromatography and found that the degradation rate was sensitive to the
      nature of the pendant groups. The metal-free polymer underwent somewhat slower
      degradation than the corresponding polymers in which the DTPA groups were
      saturated with Eu(3+) or In(3+), but even after 14 days, substantial fractions of
      the polymers survived. We conclude that these polymers undergo negligible
      degradation on the time scale (24-48 h) of radioimmunotherapy treatment of tumors
      with (111)In. From a mechanistic perspective, we note that these degradation
      rates are on the order of the deamidation rates reported [J. Peptide Res. 2004,
      63, 426] for Asn-containing pentapeptides, with half-times on the order of 10
      days, but much slower than the rapid decay (hours) reported recently
      [Biomaterials 2010, 31, 3707] for poly{N'-[N-(2-aminoethyl)-2
      aminoethyl]aspartamide} itself. This variation in degradation rate can be
      explained in terms of the influence of positive charges on the pendant group
      enhancing the acidity of the side-chain amide nitrogen of the aspartamide repeat
      unit. The DET pendant group is positively charged at pH 7, but in indium-loaded
      PAsp(DTPA) this charge is offset by the net negative charge of the DTPA-In
      complex.

PMID- 22471755
TI  - The relationship between aortic stiffness and left ventricular dyssynchrony in
      hypertensive patients with preserved left ventricular systolic function.
AB  - Left ventricular (LV) dyssynchrony is often seen in patients with hypertension,
      even without heart failure. Arterial stiffness is well accepted as an important
      factor of increasing blood pressure and influencing ventricular function. The
      purpose of this study was to determine the relationship between aortic stiffness
      and LV dyssynchrony in hypertensive patients with preserved LV systolic function.
      Eighty hypertensive patients with preserved LV systolic function (LV ejection
      fraction > 50%) and 30 controls were studied. The LV systolic and diastolic
      dyssynchrony indices were determined as the standard deviation of the time
      interval from onset of the QRS complex to peak myocardial systolic velocity (Ts
      SD) and to early diastolic velocity (Te-SD) and the maximal differences in Ts (Ts
      Max) and Te (Te-Max) in 12 LV segments. Aortic stiffness index was calculated
      from aortic diameters in the systolic and diastolic phases, as measured by
      echocardiography and blood pressure. No relationship was observed between LV
      systolic and diastolic dyssynchrony indices (r = 0.057, P = .61). In simple
      regression, aortic stiffness parameter was related to left ventricular mass index
      (LVMI), E/A ratio, and LV diastolic dyssynchrony index. But using multiple linear
      regression, Te-Max remained as a single variable related to aortic strain and
      aortic stiffness index (r = -0.271, P = .008 and r = 0.269, P = .008). LVMI was
      related to aortic distensibility using multiple linear regression (r = -0.239, P
      = .02). Aortic stiffness index was related to LV diastolic dyssynchrony index and
      LVMI. These findings suggest that LV diastolic dyssynchronous changes may be
      caused by increased LV mass and arterial stiffness.

PMID- 22471756
TI  - Diastereo- and enantioselective [3 + 2] cycloaddition reaction of Morita-Baylis
      Hillman carbonates of isatins with N-phenylmaleimide catalyzed by Me-DuPhos.
AB  - A Me-DuPhos-catalyzed efficient asymmetric [3 + 2] cycloaddition reaction between
      Morita-Baylis-Hillman carbonates of isatins and N-phenylmaleimide has been
      developed. This reaction constructs three chiral centers in one step to afford
      spirocyclopentaneoxindoles in good yields (up to 84%) with excellent diastereo-
      and enantioselectivies (up to 99% ee).

PMID- 22471757
TI  - Electronic cigarettes: achieving a balanced perspective.
AB  - Concerns have been raised that the advent of electronic cigarettes (e-cigarettes)
      may be harmful to public health, and smokers have been advised by important
      agencies such as the US Food and Drug Administration not to use them. This paper
      argues that, while more research is needed on the cost-benefit equation of these
      products and the appropriate level and type of regulation for them, the harms
      have tended thus far to be overstated relative to the potential benefits. In
      particular: concern over repeated inhalation of propylene glycol is not borne out
      by toxicity studies with this compound; risk of accidental poisoning is no
      different from many household devices and chemicals available in supermarkets;
      concern that e-cigarettes may promote continued smoking by allowing smokers to
      cope with no-smoking environments is countered by the observation that most
      smokers use these products to try to quit and their use appears to enhance
      quitting motivation; concerns over low nicotine delivery are countered by
      evidence that the products provide significant craving reduction despite this in
      some cases; and e-cigarettes may help reduce toxin exposure to non-smokers.

PMID- 22471758
TI  - Complementary and alternative medicine use among older Australian women--a
      qualitative analysis.
AB  - BACKGROUND: The use of complementary and alternative medicines (CAM) among older
      adults is an emerging health issue, however little is known about older people's
      experiences of using CAM and the cultural, geographical and other determinants of
      CAM use in this population. This study used qualitative methods to explore older
      women's views of CAM and reasons for their use of CAM. Participants for the
      project were drawn from the Australian Longitudinal Study on Women's Health
      (ALSWH) 1921-1926 birth cohort. Women who responded positively to a question
      about CAM use in Survey 5 (2008) of the ALSWH were invited to participate in the
      study. A total of 13 rural and 12 urban women aged between 83 and 88 years agreed
      to be interviewed. RESULTS: The women expressed a range of views on CAM which
      fell into three broad themes: "push" factors such as dissatisfaction with
      conventional health services, "pull" factors which emphasised the positive
      aspects of choice and self-care in health matters, and barriers to CAM use.
      Overall, the "push' factors did not play a major role in the decision to use CAM,
      rather this was driven by "pull" factors related to health care self
      responsibility and being able to source positive information about types of CAM.
      A number of barriers were identified such as access difficulties associated with
      increased age, limited mobility and restricted transport options, as well as
      financial constraints. CONCLUSIONS: CAM use among older women was unlikely to be
      influenced by aspects of conventional health care ("push factors"), but rather
      was reflective of the personal beliefs of the women and members of their close
      social networks ("pull factors"). While it was also apparent that there were
      differences between the rural and urban women in their use of CAM, the reasons
      for this were mainly due to the difficulties inherent in accessing certain types
      of CAM in rural areas.

PMID- 22471759
TI  - The impact of pesticide suicide on the geographic distribution of suicide in
      Taiwan: a spatial analysis.
AB  - BACKGROUND: Pesticide self-poisoning is the most commonly used suicide method
      worldwide, but few studies have investigated the national epidemiology of
      pesticide suicide in countries where it is a major public health problem. This
      study aims to investigate geographic variations in pesticide suicide and their
      impact on the spatial distribution of suicide in Taiwan. METHODS: Smoothed
      standardized mortality ratios for pesticide suicide (2002-2009) were mapped
      across Taiwan's 358 districts (median population aged 15 or above = 27 000), and
      their associations with the size of agricultural workforce were investigated
      using Bayesian hierarchical models. RESULTS: In 2002-2009 pesticide poisoning was
      the third most common suicide method in Taiwan, accounting for 13.6% (4913/36
      110) of all suicides. Rates were higher in agricultural East and Central Taiwan
      and lower in major cities. Almost half (47%) of all pesticide suicides occurred
      in areas where only 13% of Taiwan's population lived. The geographic distribution
      of overall suicides was more similar to that of pesticide suicides than non
      pesticide suicides. Rural-urban differences in suicide were mostly due to
      pesticide suicide. Areas where a higher proportion of people worked in
      agriculture showed higher pesticide suicide rates (adjusted rate ratio [ARR] per
      standard deviation increase in the proportion of agricultural workers = 1.58, 95%
      Credible Interval [CrI] 1.44-1.74) and overall suicide rates (ARR = 1.06, 95% CrI
      1.03-1.10) but lower non-pesticide suicide rates (ARR = 0.91, 95% CrI 0.87-0.95).
      CONCLUSION: Easy access to pesticides appears to influence the geographic
      distribution of suicide in Taiwan, highlighting the potential benefits of
      targeted prevention strategies such as restricting access to highly toxic
      pesticides.

PMID- 22471760
TI  - In situ TEM near-field optical probing of nanoscale silicon crystallization.
AB  - Laser-based processing enables a wide variety of device configurations comprising
      thin films and nanostructures on sensitive, flexible substrates that are not
      possible with more traditional thermal annealing schemes. In near-field optical
      probing, only small regions of a sample are illuminated by the laser beam at any
      given time. Here we report a new technique that couples the optical near-field of
      the laser illumination into a transmission electron microscope (TEM) for real
      time observations of the laser-materials interactions. We apply this technique to
      observe the transformation of an amorphous confined Si volume to a single crystal
      of Si using laser melting. By confinement of the material volume to nanometric
      dimensions, the entire amorphous precursor is within the laser spot size and
      transformed into a single crystal. This observation provides a path for laser
      processing of single-crystal seeds from amorphous precursors, a potentially
      transformative technique for the fabrication of solar cells and other
      nanoelectronic devices.

PMID- 22471761
TI  - Complete mitochondrial genome of the dotted gizzard shad Konosirus punctatus
      (Teleostei, Clupeidae).
AB  - The complete mitochondrial genome of the dotted gizzard shad Konosirus punctatus
      (Teleostei, Clupeidae) has been determined. The entire sequence is 16,706 bp in
      length, with a gene content (13 protein-coding genes, 2 ribosomal RNAs, 22
      transfer RNAs and 1 control region) and organization similar to that observed in
      most other vertebrates. Overall base composition of the light strand was
      represented as 25.8% of A, 29.0% of C, 25.1% of T and 20.1% of G. With the
      exception of ND6 and eight tRNA genes, all other mitochondrial genes are encoded
      on the heavy strand. Tandem repeat sequences were observed in the control region,
      indicating a useful marker for population genetic studies.

PMID- 22471762
TI  - High intensity and prevalence of two species of trematode metacercariae in the
      fathead minnow (Pimephales promelas) with no compromise of minnow anti-predator
      competence.
AB  - Opportunity for parasites to manipulate host behavioral phenotype may be
      influenced by several factors, including the host ecology and the presence of
      cohabiting parasites in the same host. Metacercariae of Ornithodiplostomum
      ptychocheilus and "black spot" Crassiphiala bulboglossa have similar life cycles.
      Each parasite uses a littoral snail as a first intermediate host, fathead minnows
      as a second intermediate host, and a piscivorous bird as a final host.
      Metacercariae of black spot encyst in the dermal and epidermal tissues, while
      metacercariae of O. ptychocheilus encyst on the brain over a region that
      coordinates optomotor responses. Because of site differences within the host, we
      predicted that O. ptychocheilus metacercariae might manipulate the behavioral
      phenotype of minnows to facilitate transmission to the final host, but
      metacercariae of black spot would not. In our study population, prevalence was
      100% for O. ptychocheilus , with an overall median intensity of 105 metacercariae
      per minnow. Prevalence of black spot was 60%, with a median abundance and
      intensity of 12 and 20 metacercariae per minnow for the overall sample and for
      infected fish, respectively. Minnows accumulated both parasites over time,
      producing significant correlations between intensity and minnow body length and
      between intensities of the 2 parasites. Minnows infected with black spot had on
      average twice as many O. ptychocheilus metacercariae as similar-sized minnows
      without any black spot cercariae. We found no correlation between body condition
      of minnows and intensity for either parasite. We measured 2 aspects of anti
      predator competence to test for effects linked to parasite intensity. We found no
      correlation between intensity of either species of parasite and latency to
      behavioral response to attack from a mechanical model heron, nor was there any
      effect of parasite intensity on a measure of shoaling affinity. The absence of
      any detectable effect of metacercariae on anti-predator competence in minnows may
      reflect selection against parasite pathology from predation by non-hosts of the
      parasites and overwinter mortality due to low dissolved oxygen.

PMID- 22471763
TI  - 'Chaos, restitution and quest': one woman's journey through menopause.
AB  - Menopause, a natural stage in a woman's reproductive life, is not an illness; yet
      some women experience severe enough symptoms to cause a breakdown in the body
      similar to illness or other major health disruptions. As part of a larger
      narrative analysis investigation of distress during menopause, this case study
      presents one woman's transformational journey through menopause, analysed through
      Frank's health and illness narratives - chaos, restitution and quest. The
      narratives were retranscribed using Labov's elements of a true story and Gee's
      poetic restructuring. This report of one woman's experience of distress during
      the menopause transition describes a poetic chaos narrative of incessant night
      sweats resulting in a loss of physicality and a deep-rooted belief in self
      healing; a restitution narrative of restored health that mandated the surrender
      to a new healing discourse, experienced simultaneously as a victory and a defeat;
      and a quest narrative of seeking meaning, insight and new-found values and
      identities.

PMID- 22471764
TI  - tkt1, located on a novel pathogenicity island, is prevalent in avian and human
      extraintestinal pathogenic Escherichia coli.
AB  - BACKGROUND: Extraintestinal pathogenic Escherichia coli are important pathogens
      of human and animal hosts. Some human and avian extraintestinal pathogenic E.
      coli are indistinguishable on the basis of diseases caused, multilocus sequence
      and phylogenetic typing, carriage of large virulence plasmids and traits known to
      be associated with extraintestinal pathogenic E. coli virulence. RESULTS: The
      gene tkt1 identified by a previous signature-tagged transposon mutagenesis study,
      was found on a 16-kb genomic island of avian pathogenic Escherichia coli (APEC)
      O1, the first pathogenic Escherichia coli strain whose genome has been completely
      sequenced. tkt1 was present in 39.6% (38/96) of pathogenic Escherichia coli
      strains, while only 6.25% (3/48) of E. coli from the feces of apparently healthy
      chickens was positive. Further, tkt1 was predominantly present in extraintestinal
      pathogenic E. coli belonging to the B2 phylogenetic group, as compared to
      extraintestinal pathogenic E. coli of other phylogenetic groups. The tkt1
      containing genomic island is inserted between the metE and ysgA genes of the E.
      coli K12 genome. Among different extraintestinal pathogenic E. coli of the B2
      phylogenetic group, 61.7% of pathogenic Escherichia coli, 80.6% of human
      uropathogenic E.coli and 94.1% of human neonatal meningitis-causing E. coli,
      respectively, harbor a complete copy of this island; whereas, only a few avian
      fecal E. coli strains contained the complete island. Functional analysis showed
      that Tkt1 confers very little transketolase activity but is involved in peptide
      nitrogen metabolism. CONCLUSION: These results suggest tkt1 and its corresponding
      genomic island are frequently associated with avian and human ExPEC and are
      involved in bipeptide metabolism.

PMID- 22471765
TI  - EMMPRIN levels in amyotrophic lateral sclerosis.

PMID- 22471766
TI  - Relationship between vitamin D and depression in multiple sclerosis.

PMID- 22471768
TI  - A novel beta-globin gene mutation HBB.c.22 G>C produces a hemoglobin variant (Hb
      Vellore) mimicking HbS in HPLC.
AB  - Hemoglobinopathies are highly prevalent in Indian population. DNA analysis to
      detect causative mutations is required for identifying rare hemoglobin variants
      or when hematological results are discordant with the clinical phenotype. In this
      report, we describe a novel hemoglobin variant caused by a mutation in beta
      globin gene, Codon 7 GAG->CAG (Glu->Gln) that elutes in the position of sickle
      haemoglobin (HbS) in cation exchange high performance liquid chromatography. This
      report highlights possible diagnostic pitfalls in interpreting data solely based
      on haemoglobin analysis and usefulness of mutation screening in definitive
      diagnosis of hemoglobinopathies.

PMID- 22471769
TI  - Inbreeding avoidance mechanisms: dispersal dynamics in cooperatively breeding
      southern pied babblers.
AB  - 1. Breeding with kin can reduce individual fitness through the deleterious
      effects of inbreeding depression. Inbreeding avoidance mechanisms are expected to
      have developed in most species, and especially in cooperatively breeding species
      where individuals may delay dispersal until long after sexual maturity. Such
      potential mechanisms include sex-biased dispersal and avoidance of kin known
      through associative learning. 2. The investigation of inbreeding avoidance
      through dispersal dynamics can be enhanced by combining fine-scale population
      genetic structure data with detailed behavioural observations of wild
      populations. 3. We investigate possible inbreeding avoidance in a wild population
      of cooperatively breeding southern pied babblers (Turdoides bicolor). A
      combination of genetic, geographic and observational data is used to examine fine
      scale genetic structure, dispersal (including sex-biased dispersal) and
      inheritance of dominance in cooperatively breeding groups. 4. Unusually, sex-bias
      in dispersal distance does not occur. Rather, individuals appear to avoid
      inbreeding through two routes. First, through dispersal itself: although both
      males and females disperse locally, they move outside the range within which
      genetically similar individuals are usually found, going twice as far from natal
      groups as from non-natal groups. Second, through avoidance of familiar group
      members as mates: individuals inherit a dominant position in the natal group only
      when an unrelated breeding partner is present. 5. This study uses spatial genetic
      analyses to investigate inbreeding avoidance mechanisms in a cooperative breeder
      and shows that individuals of both sexes can avoid inbreeding through a dispersal
      distance mechanism. While it appears that dispersal allows most individuals to
      move beyond the range of closely related kin, matings may still occur between
      distant kin. Nevertheless, any costs of breeding with a distant relative may be
      outweighed by the benefits of local dispersal and the immense fitness gains
      available from attaining a breeding position.

PMID- 22471770
TI  - Temperature-dependent, effective structures of the 14NH3 and 14ND3 molecules.
AB  - Measurements result in effective, usually temperature-dependent structural
      parameters of molecules, and never directly in equilibrium structures, which are
      theoretical constructs. A recent high-accuracy semiglobal potential energy
      surface of the electronic ground state of the ammonia molecule, called NH3-Y2010
      (J. Mol. Spectrosc. 2011, 268, 123), which exhibits mass-independent equilibrium
      NH bond length and a HNH bond angle of 1.0109 A and 106.75 degrees ,
      respectively, is employed together with the variational nuclear motion code
      GENIUSH (J. Chem. Phys. 2009, 130, 134112; 2011, 134, 074105) to determine
      directly measurable, effective structural parameters of the (14)NH(3) and
      (14)ND(3) molecules. The effective r(g)- and r(a)-type NH(ND) distances
      determined at 300 K are 1.0307(1.0254) and 1.0256(1.0217) A, respectively, with
      an estimated accuracy of 2 * 10(-4) A. The effective theta(g) HNH and DND bond
      angles at 300 K are 106.91 degrees  and 106.85 degrees , respectively. The root
      mean-square amplitudes of vibration, l(g), for the NH(ND) distances at 300 K are
      0.073(0.062) A. These structural parameters confirm the less accurate results of
      a room-temperature gas-electron-diffraction study (J. Chem. Phys. 1968, 49, 2488,
      all data in A): r(g)(NH) = 1.030(2), l(g)(NH) = 0.073(2), r(g)(ND) = 1.027(3),
      and l(g)(ND) = 0.061(2). The computed difference in the r(g,T)(NH) bond lengths
      of the two spin isomers (ortho and para forms) of (14)NH(3) is 3 * 10(-5) A at 0
      K, the difference diminishes at temperatures of about 30-50 K.

PMID- 22471772
TI  - Roads towards a new tailored therapy for hepatocellular carcinoma: diagnostic,
      therapeutic and prognostic implications of microRNAs.

PMID- 22471773
TI  - Brushing of bile duct stenoses for the true dignity.

PMID- 22471771
TI  - Understanding aggressive behaviour across the lifespan.
AB  - Aggressive behaviour is the observable manifestation of aggression and is often
      associated with developmental transitions and a range of medical and psychiatric
      diagnoses across the lifespan. As healthcare professionals involved in the
      medical and psychosocial care of patients from birth through death, nurses
      frequently encounter - and may serve as - both victims and perpetrators of
      aggressive behaviour in the workplace. While the nursing literature has
      continually reported research on prevention and treatment approaches, less
      emphasis has been given to understanding the aetiology, including contextual
      precipitants of aggressive behaviour. This paper provides a brief review of the
      biological, social and environmental risk factors that purportedly give rise to
      aggressive behaviour. Further, many researchers have focused specifically on
      aggressive behaviour in adolescence and adulthood. Less attention has been given
      to understanding the aetiology of such behaviour in young children and older
      adults. This paper emphasizes the unique risk factors for aggressive behaviour
      across the developmental spectrum, including childhood, adolescence, adulthood
      and late life. Appreciation of the risk factors of aggressive behaviour, and, in
      particular, how they relate to age-specific manifestations, can aid nurses in
      better design and implementation of prevention and treatment programmes.

PMID- 22471775
TI  - Polymer composites reinforced by locking-in a liquid-crystalline assembly of
      cellulose nanocrystallites.
AB  - An attempt was made to synthesize novel composites comprising poly(2-hydroxyethyl
      methacrylate) (PHEMA) and cellulose nanocrystallites (CNC) (acid-treated cotton
      microfibrils) from suspensions of CNC in an aqueous 2-hydroxyethyl methacrylate
      (HEMA) monomer solution. The starting suspensions (~5 wt % CNC) separated into an
      isotropic upper phase and an anisotropic bottom one in the course of quiescent
      standing. By way of polymerization of HEMA in different phase situations of the
      suspensions, we obtained films of three polymer composites, PHEMA-CNC(iso), PHEMA
      CNC(aniso), and PHEMA-CNC(mix), coming from the isotropic phase, anisotropic
      phase, and embryonic nonseparating mixture, respectively. All the composites were
      transparent and, more or less, birefringent under a polarized optical microscope.
      A fingerprint texture typical of cholesteric liquid crystals of longer pitch
      spread widely in PHEMA-CNC(aniso) but rather locally appeared in PHEMA-CNC(iso).
      Any of the CNC incorporations into the PHEMA matrix improved the original thermal
      and mechanical properties of this amorphous polymer material. In dynamic
      mechanical measurements, the locking-in of the respective CNC assemblies gave
      rise to an increase in the glass-state modulus E' of PHEMA as well as a marked
      suppression of the E'-falling at temperatures higher than T(g) (~ 110  degrees C)
      of the vinyl polymer. It was also observed for the composites that their modulus
      E' rerose in a range of about 150-190  degrees C, which was attributable to a
      secondary cross-linking formation between PHEMA chains mediated by the acidic CNC
      filler. The mechanical reinforcement effect of the CNC dispersions was ensured in
      a tensile test, whereby PHEMA-CNC(aniso) was found to surpass the other two
      composites in stiffness and strength.

PMID- 22471777
TI  - Smokeless tobacco use among operating engineers.
AB  - Workers in blue collar occupations have been shown to have higher rates of
      smokeless tobacco (ST) use compared to other occupational groups. Guided by the
      Health Promotion Model, the purpose of this study was to understand various
      factors that predict ST use in Operating Engineers. A cross-sectional design was
      used to determine variables related to ST use among Operating Engineers.
      Engineers (N = 498) were recruited during their 3-day apprentice certification
      course to participate in the study. Logistic regression was used to assess the
      associations between personal, psychological and behavioral characteristics
      associated with ST use. Past month ST use was reported among 13% of operating
      engineers surveyed. Multivariate analysis showed that younger age and lower rates
      of past month cigarette use were significantly associated with ST use, while
      higher rates of problem drinking were marginally associated with ST use.
      Operating Engineers are at high risk for using ST products with rates in this
      sample well over the national average. Work site interventions, which have shown
      promise in other studies, may be useful in decreasing ST use among this
      population.

PMID- 22471778
TI  - Beliefs and norms associated with smoking tobacco using a waterpipe among college
      students.
AB  - This web-based, cross-sectional survey guided by the Theory of Reasoned Action
      (TRA), examined behavioral beliefs and normative beliefs associated with smoking
      tobacco using a waterpipe in a sample of 223 undergraduate college students.
      Beliefs and norms associated with waterpipe smoking intention were captured using
      the investigator-developed TRA Waterpipe Questionnaire. Significant behavioral
      beliefs that contributed to the prediction of smoking intentions included smoking
      tobacco with a waterpipe "will taste pleasant" and "will allow me to have a good
      time with my friends." Significant norms that emerged were perceived approval of
      waterpipe smoking from friends and significant others. Current smoking status,
      both waterpipe and cigarette, also contributed to the prediction of smoking
      intention. The variables of the TRA represent prime targets for intervention and
      provide useful information that can be used to tailor waterpipe prevention
      messages.

PMID- 22471779
TI  - Baseline characteristics of college freshmen enrolled in an alcohol intervention
      program.
AB  - This study is a baseline analysis of the demographic and behavioral
      characteristics of freshmen students recruited to enter a longitudinal multi
      component intervention program based on the Brief Alcohol Screening, and
      Intervention for College Students (BASICS) program. The aim of the study was to
      determine the associations among the participants' gender, ethnicity, age,
      drinking, psychological problems, sexual contacts, and illegal substance use.
      Freshmen participants (n = 186) were between the ages of 18 and 20 with a mean
      age of 18.51 +/- 0.62, and 37.6% of the participants were males. Three surveys
      were administered at baseline: the Daily Drinking Questionnaire (DDQ;  Collins,
      Parks, & Marlatt, 1985 ); Rutgers Alcohol Problem Index (RAPI;  White & Labouvie,
      1989 ), Government Performance and Results Act (GPRA;  Office of Management and
      Budget [OMB], 1993 ), Client Outcome Measures for Discretionary Programs and Best
      Practices grantees. Descriptive statistics were used to determine the behavioral
      characteristics. During past 30 days participants on average consumed alcohol on
      7.3 +/- 5.2 days, used illegal substances 3.0 +/- 7.2 days and had 5.3 +/- 7.0
      sexual contacts and less 2.1 +/- 4.6 unprotected sexual contacts (USC). Results
      of this baseline analysis demonstrate the diversity of the program participant
      demographic characteristics and behavioral patterns. This study contributes
      valuable implications for the design of interventions programs to address high
      risk behaviors among freshmen college students.

PMID- 22471780
TI  - Hookah use: going down in smoke.
AB  - This article provides a review of tobacco smoking using a hookah, an emerging
      threat to public health, especially among young adults. Knowledge deficits
      persist in regards to this form of smoking, because many perceive it as less
      harmful than cigarette smoking and little research is available. Knowledge about
      hookah smoking can be instrumental in guiding health professionals to address
      this practice with their clients and in their communities. A failure to address
      all tobacco products as unique, individual entities undermines any success in
      public policy efforts to control tobacco use.

PMID- 22471781
TI  - Adolescents and inhalant abuse: how huffing affects the myelin sheath.
AB  - As concern grows over the impact that accidental chemical exposures may have on
      the long term health of individuals, our young people are deliberately exposing
      themselves to the effect of neurotoxic chemicals with the intent of feeling high.
      Over time the result of inhaling these chemicals is often the development of
      symptoms and behavior that may suggest serious physiological damage. Research is
      being conducted to examine what the exact nature of the damage might be,
      especially the impact of inhaled lipophilic chemicals on structures in the brain
      and other parts of the nervous system. Healthcare professionals responsible for
      assessing adolescents in all settings need to be aware of the prevalence of
      inhalant abuse, as well as the chemicals, terminology, and potential
      symptomatology in order to intervene in the behavior and provide diagnosis and
      treatment as indicated. Some implications for nursing are included.

PMID- 22471782
TI  - Association between nondipper behavior and serum calcium in hypertensive patients
      with mild-to-moderate chronic renal dysfunction.
AB  - A nondipping BP pattern has been shown to be predictive of end-organ damage,
      cardiovascular events, and mortality. The mechanisms of blunted nocturnal BP fall
      are multifactorial. We assessed whether total corrected serum calcium and ionic
      calcium (iCa) are associated with a blunted nocturnal BP fall in both treated and
      untreated hypertensive patients with stages 1-3 of the National Kidney Foundation
      Kidney Disease Outcomes Quality Initiative (NKF KDOQI). Clinical data and 24-hour
      ambulatory blood pressure monitoring were obtained in a cohort of 231 essential
      hypertensive patients. Among the entire cohort, 107 were nondippers and 124 were
      dippers. Only in nondippers, we found significant correlations between iCa and 24
      hour systolic blood pressure (SBP; r = 0.21, P < .03), diurnal SBP (r = 0.21, P <
      .03), and 24-hour pulse pressure (PP; r = 0.23, P < .02). The ambulatory arterial
      stiffness index (AASI) was significantly related with 24-hour PP in both dippers
      and nondippers after adjusting for age. Both AASI and 24-hour PP were higher in
      nondippers than in dippers. In addition, in nondippers, the prevalence of
      estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m2 was higher
      than in dippers (50% vs. 33.7%, P < .02). Logistic regression showed that
      patients with eGFR >= 60 mL/minute/1.73 m2 had lower risk of nondipper status
      than patients with eGFR < 60 mL/minute/1.73 m2 (odds ratio = 2.445; 95%
      confidence interval = 1.398-4.277, P < .002). In conclusion, serum iCa could
      participate in the pathogenesis of nondipping pattern. Increased large artery
      stiffness may be a mechanism of the deleterious influence of nondipping on
      cardiovascular outcome. Hypertensive subjects with stage 3 of NKF KDOQI had a
      greater loss of circadian BP rhythm than those in stages 1 and 2.

PMID- 22471783
TI  - FlexTouch(r) for the delivery of insulin: technical attributes and perception
      among patients and healthcare professionals.
AB  - Insulin injection pens have improved the ease and convenience of administering
      insulin for people with diabetes. This article reviews the data on a new
      prefilled insulin pen, FlexTouch(r). FlexTouch has a novel injection mechanism
      with no push-button extension and a lower injection force than other prefilled
      pens, and other features including an end-of-dose click; a large dose display;
      color-coded pens to distinguish different insulin types; an ergonomic design; and
      compatibility with both NovoTwist(r) needles and most screw-thread needles.
      FlexTouch has been demonstrated to deliver insulin consistently and accurately at
      minimum, half-maximum and maximum doses. In usability studies recruiting patients
      and healthcare professionals, FlexTouch was easier to use and instilled more
      confidence than other prefilled pens, and was preferred to other prefilled pens.
      FlexTouch was also found to be easier to use and was preferred for learning and
      teaching to use.

PMID- 22471784
TI  - Minimalist probes for studying protein dynamics: thioamide quenching of
      selectively excitable fluorescent amino acids.
AB  - Fluorescent probe pairs that can be selectively excited in the presence of Trp
      and Tyr are of great utility in studying conformational changes in proteins.
      However, the size of these probe pairs can restrict their incorporation to small
      portions of a protein sequence where their effects on secondary and tertiary
      structure can be tolerated. Our findings show that a thioamide bond-a single atom
      substitution of the peptide backbone-can quench fluorophores that are red-shifted
      from intrinsic protein fluorescence, such as acridone. Using steady-state and
      fluorescence lifetime measurements, we further demonstrate that this quenching
      occurs through a dynamic electron-transfer mechanism. In a proof-of-principle
      experiment, we apply this technique to monitor unfolding in a model peptide
      system, the villin headpiece HP35 fragment. Thioamide analogues of the natural
      amino acids can be placed in a variety of locations in a protein sequence,
      allowing one to make a large number of measurements to model protein folding.

PMID- 22471785
TI  - In vitro cytotoxicity of Strobilanthes crispus ethanol extract on hormone
      dependent human breast adenocarcinoma MCF-7 cell.
AB  - BACKGROUND: Strobilanthes crispus has been traditionally used as antidiabetic,
      anticancer, diuretic, antilytic and laxative agent. However, cytotoxicity and
      antiproliferative effect of S. crispus is still unclear. RESULTS: Strobilanthes
      cripus was able to reduce cell viability and proliferation in MTT and BrdU
      assays. Both cell cycle progression and Tunel assay suggested that IC50 of S.
      crispus ethanol extract induced sub-G1 cell cycle phase, and DNA fragmentation.
      On the other hand, translocation of mitochondria cytochrome c release, induction
      of caspase 3/7 and p53 while suppress XIAP on treated MCF-7 cell were also
      observed in this study. CONCLUSION: Our findings suggest that S. crispus ethanol
      extract induced apoptosis and DNA fragmentation on hormone dependent breast
      cancer cell line MCF-7 via mitochondria dependent p53 apoptosis pathway.

PMID- 22471786
TI  - Metastatic cutaneous involvement of granulomatous colitis in Hermansky-Pudlak
      syndrome.
AB  - Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disorder
      characterized by oculocutaneous albinism, a hemorrhagic diathesis due to platelet
      dysfunction, and lysosomal ceroid accumulation that can cause a Crohn's-like
      granulomatous colitis and pulmonary fibrosis. We report peristomal and vulvar
      cutaneous involvement of the granulomatous colitis in HPS. 

PMID- 22471787
TI  - The effectiveness of financial incentives for smoking cessation during pregnancy:
      is it from being paid or from the extra aid?
AB  - BACKGROUND: Financial incentives appear to be effective in promoting smoking
      cessation in pregnancy. The mechanisms by which they might operate however, are
      poorly understood. The present study examines how financial incentives for
      smoking cessation during pregnancy may work, by exploring pregnant women's
      experiences of trying to stop smoking, within and outside of a financial
      incentives scheme. METHODS: Thirty-six (n = 36) UK-based pregnant smokers (n =
      36), offered standard NHS Stop-Smoking Services, of whom twenty (n = 20) were
      enrolled in a financial incentives scheme for smoking cessation (n = 20) and
      sixteen (n = 16) were not, were interviewed about (i) their motivation to stop
      smoking, and (ii) the factors they perceived as influencing their quitting
      efforts. Framework Analysis was used to analyse the data. RESULTS: Women in the
      two groups reported similar reasons for wanting to stop smoking during pregnancy.
      However, they described dissimilar experiences of the Stop-Smoking Services,
      which they perceived to have differentially influenced their quit attempts. Women
      who were incentivised reported using the services more than women who were not
      incentivised. In addition, they described the motivating experience of being
      monitored and receiving feedback on their progress. Non-incentivised women
      reported problems receiving the appropriate Nicotine Replacement Therapy, which
      they described as having a detrimental effect on their quitting efforts.
      CONCLUSION: Women participating in a financial incentives scheme to stop smoking
      reported greater engagement with the Stop-Smoking Services, from which they
      described receiving more help in quitting than women who were not part of the
      scheme. These results highlight the complexity of financial incentives schemes
      and the intricacies surrounding the ways in which they operate to affect smoking
      cessation. These might involve influencing individuals' motivation and self
      regulation, changing engagement with and provision of support services, or a
      combination of these.

PMID- 22471788
TI  - Aggregatibacter actinomycetemcomitans serotypes, the JP2 clone and cytolethal
      distending toxin genes in a Thai population.
AB  - AIM: To examine the genetic diversity of Aggregatibacter actinomycetemcomitans in
      Thai adults. MATERIALS AND METHODS: Subgingival plaque samples from 453 subjects
      were analysed for A. actinomycetemcomitans serotypes, the presence of the high
      leukotoxin-producing JP2 clone and cytolethal distending toxin genes (cdtABC)
      using the polymerase chain reaction technique. In subjects who were positive for
      cdtABC, restriction fragment length polymorphism analysis was used to identify a
      single nucleotide polymorphism (SNP) in the cdtB gene at amino acid position 281.
      The extent and severity of periodontal disease were compared between subjects
      harbouring different A. actinomycetemcomitans genotypes. RESULTS: Eighty six
      subjects (19%) were positive for A. actinomycetemcomitans. The JP2 clone was not
      detected. Serotype c was the most prevalent (57%), followed by serotypes a (33%)
      and b (7%). Among A. actinomycetemcomitans-positive subjects, 27% were positive
      for cdtABC. All cdtABC-positive subjects possessed the SNP in the cdtB, which is
      involved with increased toxin activity. The presence of A. actinomycetemcomitans,
      but not a specific genotype, was significantly related to increased probing depth
      and periodontal attachment loss. CONCLUSIONS: Our results confirm the previous
      findings that genotype distribution of A. actinomycetemcomitans varies between
      ethnic groups. However, no clear relationship between a specific genotype and
      periodontal conditions was observed.

PMID- 22471789
TI  - Palladium-catalyzed cascade process to construct 1,2,5-trisubstituted pyrroles.
AB  - A novel palladium-catalyzed cascade allylic amination/intramolecular
      hydroamination/isomerization process of protected enynol 1 and primary amine 2
      has been explored, which constructs the important 1,2,5-trisubstituted pyrroles.
      This transformation offers an alternative synthetic methodology capable of
      generating substituted pyrroles in a straightforward way.

PMID- 22471790
TI  - Peri-implant bone formation and surface characteristics of rough surface zirconia
      implants manufactured by powder injection molding technique in rabbit tibiae.
AB  - OBJECTIVE: To evaluate osseointegration in rabbit tibiae and to investigate
      surface characteristics of novel zirconia implants made by powder injection
      molding (PIM) technique, using molds with and without roughened inner surfaces.
      MATERIAL AND METHODS: A total of 20 rabbits received three types of external hex
      implants with identical geometry on the tibiae: machined titanium implants, PIM
      zirconia implants without mold etching, and PIM zirconia implants with mold
      etching. Surface characteristics of the three types of implant were evaluated.
      Removal torque tests and histomorphometric analyses were performed. RESULTS: The
      roughness of PIM zirconia implants was higher than that of machined titanium
      implants. The PIM zirconia implants exhibited significantly higher bone-implant
      contact and removal torque values than the machined titanium implants (P <
      0.001). The PIM zirconia implants using roughened mold showed significantly
      higher removal torque values than PIM zirconia implants without using roughened
      mold (P < 0.001). CONCLUSIONS: It is concluded that the osseointegration of PIM
      zirconia implant is promising and PIM using roughened mold etching technique can
      produce substantially rough surfaces on zirconia implants.

PMID- 22471791
TI  - Should young people be paid for getting tested? A national comparative study to
      evaluate patient financial incentives for chlamydia screening.
AB  - BACKGROUND: Patient financial incentives ("incentives") have been widely used to
      promote chlamydia screening uptake amongst 15-24 year olds in England, but there
      is scarce evidence of their effectiveness. The objectives of the study were to
      describe incentives used to promote chlamydia screening in Primary Care Trusts
      (PCTs) in England and to evaluate their impact on coverage and positivity rate.
      METHODS: PCTs that had used incentives between 1/1/2007 and 30/6/2009 (exposed)
      were matched by socio-demographic profile and initial screening coverage with
      PCTs that had not (unexposed). For each PCT, percentage point change in chlamydia
      screening coverage and positivity for the period before and during the incentive
      was calculated. Differences in average change of coverage and positivity rate
      between exposed and unexposed PCTs were compared using linear regression to
      adjust for matching and potential confounders. RESULTS: Incentives had a
      significant effect in increasing average coverage in exposed PCTs (0.43%, CI
      0.04%-0.82%). The effect for voucher schemes (2.35%) was larger than for prize
      draws (0.16%). The difference was greater in females (0.73%) than males (0.14%).
      The effect on positivity rates was not significant (0.07%, CI -1.53% to 1.67%).
      CONCLUSIONS: Vouchers, but not prize draws, led to a small absolute but large
      relative increase in chlamydia screening coverage. Incentives increased coverage
      more in females than males but had no impact on reported positivity rates. These
      findings support recommendations not to use prize draws to promote chlamydia
      screening and contribute to the evidence base of the operational effectiveness of
      using patient incentives in encouraging public health action.

PMID- 22471792
TI  - Integrated all-optical infrared switchable plasmonic quantum cascade laser.
AB  - We report a type of infrared switchable plasmonic quantum cascade laser, in which
      far field light in the midwave infrared (MWIR, 6.1 MUm) is modulated by a near
      field interaction of light in the telecommunications wavelength (1.55 MUm). To
      achieve this all-optical switch, we used cross-polarized bowtie antennas and a
      centrally located germanium nanoslab. The bowtie antenna squeezes the short
      wavelength light into the gap region, where the germanium is placed. The
      perturbation of refractive index of the germanium due to the free carrier
      absorption produced by short wavelength light changes the optical response of the
      antenna and the entire laser intensity at 6.1 MUm significantly. This device
      shows a viable method to modulate the far field of a laser through a near field
      interaction.

PMID- 22471793
TI  - Prevalence and intensity of fish-borne zoonotic trematodes in cultured freshwater
      fish from rural and urban areas of northern Vietnam.
AB  - Consumption of raw freshwater fish produced in both rural farm and urban
      wastewater ponds is a common practice in Vietnam. The present study assessed the
      risk of fish-borne zoonotic trematode (FZT) infection from fish raised in both
      these aquaculture systems in northern Vietnam. The diversity, prevalence, and
      infection intensity of FZT metacercariae in 1,500 freshwater fish collected from
      6 sites located in rural and urban areas in northern Vietnam were investigated.
      The specific diagnosis of species was made by morphologic methods. The overall
      FZT prevalence in fish from both urban wastewater ponds and rural farm ponds was
      11.2%. In wastewater ponds, the overall prevalence was 5.1%, ranging from 2.0% in
      tilapia to 7.3% in common and grass carp. In fish from farm ponds, the prevalence
      was 17.3%, and ranged from 6.7% in mud carp to 26.7% in common carp. The mean
      intensity of FZT infection was also higher in fish from farm ponds than that in
      fish from wastewater ponds (6.0% and 8.4%, respectively). The FZT species
      recovered from infected fish included both liver (Clonorchis sinensis) and
      intestinal flukes (Haplorchis taichui, Haplorchis pumilio, and Centrocestus
      formosanus). The prevalence of FZT in fish raised in these common farm systems
      represents a significant public health risk for a population with a strong
      cultural preference for consuming raw or inadequately prepared fish. These
      research results should encourage the public health and agriculture sectors to
      conduct the risk factor research required to develop control programs for FZT.

PMID- 22471794
TI  - Understanding older peoples' decisions about the use of sleeping medication:
      issues of control and autonomy.
AB  - Poor sleep is known to impact on health and wellbeing in later life and has
      implications for the ability of older people to remain active during the day.
      Medical treatments for chronic poor sleep have primarily included the regular,
      long-term prescribing of hypnotics, which are known to impact on older people's
      health, cognitive function and quality of life. Therefore, recent policy and
      practice has focused on reducing such prescribing, on encouraging older people to
      stop taking long-term hypnotics and on finding alternative, non-pharmacological
      ways to manage poor sleep. However, little research has been undertaken to
      understand the perspectives of older people who choose not to seek professional
      help for their poor sleep, despite the potential impact of poor sleep on their
      health and ability to remain active. Through in-depth interviews with 62 older
      men and women living in their own homes in England, this article explores the
      factors that deter older people from seeking professional help for their poor
      sleep. We argue that these are located in their perceptions of the normativity of
      poor sleep in later life, their beliefs about prescription sleeping medications
      and their desire to maintain control and autonomy over their everyday and night
      lives.

PMID- 22471795
TI  - Connecting recent studies on fish vertical navigation.

PMID- 22471796
TI  - Characteristics of ovarian follicle steroidogenesis during vitellogenesis in an
      asynchronously ovulating stock of rainbow trout Oncorhynchus mykiss.
AB  - This study explored several physiological criteria that could be used to assess
      the steroidogenic condition of the ovarian follicles of individual fish of an
      asynchronously ovulating captive rainbow trout Oncorhynchus mykiss stock. In
      these fish, the date of sampling, morphological variables such as gonado-somatic
      index or ovarian follicle mass and visual assessment of the ovary provided
      accurate indications of the maturational condition of an individual. The
      physiological variables measured included the in vitro basal and cyclic adenosine
      monophosphate (cAMP)-stimulated synthesis by ovarian follicles of 17beta
      oestradiol (E(2)) and testosterone (T); in addition, quantitative reverse
      transcription (RT)-PCR was used to measure the relative expression of star and
      p450scc genes by ovarian follicles. The ratios of cAMP-stimulated E(2) and T
      synthesis to basal E(2) and T synthesis provided a reliable indication of
      differences in the steroidogenic status of the follicles of individual animals.
      On the basis of these criteria, together with the use of gene expression
      profiles, it was possible to classify individual fish as being at an early, mid
      or late-vitellogenic stage.

PMID- 22471797
TI  - Sounds produced by the cichlid fish Metriaclima zebra allow reliable estimation
      of size and provide information on individual identity.
AB  - Sounds produced by male cichlids Metriaclima zebra during aggressive interactions
      were recorded to conduct a detailed analysis and to search for potential
      individual acoustic signatures. Fish from two different size groups (small and
      large individuals) were analysed. The two groups were significantly different for
      all acoustic variables considered; six of seven features demonstrated a
      significant interindividual variability and most of them were correlated with the
      size of the emitter. A cross-validated and permuted discriminant function
      analysis (pDFA) separated the two groups and correctly classified around 50% of
      the sounds to the correct individuals. Acoustic features that best distinguished
      among males were the instantaneous frequency of sounds and the modulation of
      pulse amplitude. These results suggest that acoustic signals could bear
      information about individual identity. The long-term stability of this signature
      is likely to be weak since the signature of a growing individual may change over
      time.

PMID- 22471798
TI  - Habitat use and spatial segregation of adult spottail sharks Carcharhinus sorrah
      in tropical nearshore waters.
AB  - An array of acoustic receivers deployed in Cleveland Bay, north Queensland,
      Australia, passively tracked 20 adult spottail sharks Carcharhinus sorrah over 2
      years (2009-2010) to define patterns in movement and habitat use. Individuals
      were present in the study site for long periods, ranging from 8 to 408 days (mean
      = 185). Size and location of home ranges did not vary over time. A high level of
      segregation occurred among C. sorrah, with individuals using different types of
      habitat and showing strong attachment to specific regions. The depth of habitat
      individuals used varied between sexes. Males tended to use a narrow range of
      habitat depths within the study site (2.8-6.0 m), whereas females used shallower
      habitats (1.4-6.2 m) and displayed a seasonal shift in the depth of habitat used.
      Mean monthly habitat depth used varied by as much as 2 m for females, with
      individuals using shallower habitats during the winter months. Long-term presence
      and consistent home ranges suggest that Cleveland Bay provides important habitat
      for C. sorrah. By defining patterns in the use of nearshore habitats for C.
      sorrah, this study improves the understanding of the movement and habitat use of
      smaller-bodied coastal sharks and may help provide guidance for the management of
      their populations.

PMID- 22471799
TI  - Variation in gene expression along a salinity gradient in wild populations of the
      euryhaline black-chinned tilapia Sarotherodon melanotheron.
AB  - This study evaluated variation in expression of 11 genes within and among six
      wild populations of the black-chinned tilapia Sarotherodon melanotheron
      distributed along a salinity gradient from 0 to 100. Previous laboratory studies
      had shown that expression of these genes was sensitive to water salinity; the
      current study confirmed that a number of them also varied in expression in wild
      populations along the salinity gradient. Principal component analysis (PCA) first
      distinguished two, not mutually exclusive, sets of genes: trade-off genes that
      were highly expressed at one or other extreme of the salinity gradient and stress
      genes that were up-regulated at the two salinity extremes (i.e. a U-shaped
      expression pattern). The PCA clearly partitioned the populations into three
      groups based on their gene expression patterns and their position along the
      salinity gradient: a freshwater (GL; 0) population, four brackish and seawater
      (GB, HB, SM, SF; ranging from 20 to 50) populations and a hypersaline (SK, 100)
      population. Individual variation in gene expression was significantly greater
      within the populations at the extreme compared to intermediate salinities. These
      results reveal phenotypically plastic regulation of gene expression in S.
      melanotheron, and greater osmoregulatory and plasticity costs at extreme
      salinities, where fitness-related traits are known to be altered.

PMID- 22471800
TI  - Gymnotus capanema, a new species of electric knife fish (Gymnotiformes,
      Gymnotidae) from eastern Amazonia, with comments on an unusual karyotype.
AB  - Gymnotus capanema n. sp. is described on the basis of cytogenetic, morphometric,
      meristic and osteological data from nine specimens (one male and eight females)
      from the municipality of Capanema, Para, in the eastern Amazon of Brazil. Later,
      three additional specimens were found in museums and regarded as nontypes (not
      cytogenetically analysed). Gymnotus capanema, which occurs in sympatry with
      Gymnotus cf. carapo cytotype 2n = 42 (30m/sm + 12st/a) exhibits a novel karyotype
      for the genus, with 2n = 34 (20m/sm + 14st/a). Gymnotus capanema can be
      unambiguously diagnosed from all congeners on the basis of a combination of
      characters from external anatomy, pigmentation and osteology. The constitutive
      heterochromatin, rich in adenine-thymine (A-T) base pairs [4',6 diamidino-2
      phenylindole dihydrochloride (DAPI) positive], occurs in the centromeric region
      of all of the chromosomes, and in the pericentromeric and the entire short arm of
      some chromosomes. The nucleolar organizing region (NOR), stained by silver
      nitrate, chromomycin A(3) (CMA(3)) and 18S ribosomal (r)DNA fluorescence in situ
      hybridization (FISH), occurs in the short arm of pair 15. FISH, with telomeric
      probes did not show interstitial telomeric sequences (ITS), despite the reduced
      2n in comparison to the karyotypes of other species of Gymnotus. The karyotype of
      G. capanema, with a reduced 2n, is strikingly different from all other previously
      studied congeners.

PMID- 22471801
TI  - The missing host hypothesis: do chemical cues from predators induce life cycle
      truncation of trematodes within their fish host?
AB  - Using controlled experiments, the ability of the trematode parasite Stegodexamene
      anguillae, encysted within its intermediate fish host, the common bully
      Gobiomorphus cotidianus, was tested to indirectly detect the presence of its
      definitive host by exposing infected G. cotidianus to chemical cues from the
      definitive host, the short-finned eel Anguilla australis. The trematode can
      abbreviate its normal life cycle and achieve precocious maturity in G.
      cotidianus, or adopt the usual strategy consisting in delaying maturity until it
      reaches an A. australis. The results suggest that chemical cues from the
      definitive A. australis host do not affect the frequency of life cycle
      abbreviation in S. anguillae. Other life-history traits, such as parasite body
      size or the egg output of early-maturing parasites, were also unaffected by
      chemical cues from A. australis or from an alternative predator of G. cotidianus,
      the perch Perca fluviatilis, that is not a suitable host for the trematode.
      Therefore, factors other than A. australis host presence or abundance may be the
      important selective forces for life cycle abbreviation in this fish parasite.

PMID- 22471802
TI  - A new species of Triplophysa (Nemacheilidae: Cypriniformes), from Guangxi,
      southern China.
AB  - A new species, Triplophysa huapingensis, is described from the Hongshuihe River,
      Guangxi, China. The new species is distinguished from other species of
      Triplophysa by the following combination of characters: body covered with scales,
      lateral line complete, eyes not degenerate, dorsal fin truncate, caudal fin
      forked, tip of pelvic fin not reaching anus, eight branched rays of dorsal fin,
      six branched rays of pelvic fin, 16 branched rays of caudal fin, grey and black
      diffused blotches on dorsal and lateral head and body. A key to all recorded
      species of Triplophysa in the Xijiang River system is provided.

PMID- 22471803
TI  - Effects of body mass and temperature on routine metabolic rate of juvenile
      largemouth bronze gudgeon Coreius guichenoti.
AB  - The effects of body mass (M) and temperature (T) on routine metabolic rate (m(R)
      ) were assessed in the largemouth bronze gudgeon Coreius guichenoti, from Three
      Gorges Reservoir, Yangtze River, China. The m(R) increased with increasing M by
      factors (b-value in the equation m(R) = aM(b) ) of 0.843, 0.800, 0.767, 0.788 and
      0.822 at 10, 15, 20, 25 and 30 degrees  C, respectively. A significant
      interaction between M and T on m(R) was observed. The variation in the b-value at
      different T suggests that the b-values were not consistent with the universal
      allometric exponent 0.75. After controlling for M, the relationship between the
      normalized standard metabolic rate (m(S), mg O(2) kg(-1) h(-1)) and T was
      described by an exponential equation: m(S) = 9.89e((0.093T)) . The results
      indicate that the effects of M on m(R) depend on T. The increased water
      temperature induced by dam construction on the Yangtze River may cause a marked
      increase in energy demand by this species, with potential ecological
      consequences.

PMID- 22471804
TI  - Cryptobenthic reef fishes: depth distribution and correlations with habitat
      complexity and sea urchins.
AB  - In this study, cryptobenthic fish depth patterns and their correlations with
      habitat complexity and sea urchin densities were investigated. In general, total
      density, species richness and diversity were higher in the shallower zones (3 m),
      while evenness was higher at the 10 m depth zone. Among sites, species density
      was similar at the 10 m zone, but at the 3 m zone it varied greatly. Species
      specific depth preferences were found. Correlation between species density and
      habitat complexity was usually positive. The influence of sea urchin densities on
      the cryptobenthic fish assemblage was site and species dependent.

PMID- 22471805
TI  - Characterization of yellow grouper Epinephelus awoara (Serranidae) karyotype by
      chromosome bandings and fluorescence in situ hybridization.
AB  - The cytogenetics of yellow grouper Epinephelus awoara was studied using multiple
      cytogenetic markers [Giemsa staining, C-banding, Ag-NORs and fluorescence in situ
      hybridization (FISH)]. Giemsa staining results showed that the karyotypic formula
      of E. awoara was 2n = 48a, FN (fundamental number) = 48. Faint C-bandings were
      only detected at the centromeric regions of chromosome pair number 24, being
      almost indiscernible on the other chromosome pairs. After Ag-NOR staining, one
      pair of nucleolar organizer regions (NOR) was observed in the subcentromeric
      region of pair number 24. FISH results showed that 5S rDNA was located at a pair
      of medium-sized chromosomes, while 18S rDNA appeared at the same location in the
      subcentromeric region of pair number 24 where Ag-NORs were detected. The
      telomeric sequence (TTAGGG)(n)  detected by FISH was located at both ends of each
      chromosome. The results suggested that E. awoara has retained general karyotypic
      structure stability during the evolutionary diversification process.

PMID- 22471806
TI  - The effect of adrenaline on the temperature dependency of cardiac action
      potentials in pink salmon Oncorhynchus gorbuscha.
AB  - Using sharp electrode impalement, action potentials recorded from atrial and
      ventricular tissue of pink salmon Oncorhynchus gorbuscha generally decreased in
      duration with increasing test temperature (6, 10, 16 and 20 degrees  C).
      Stimulation of the tissue using 500 nM adrenaline had no significant effect on
      the duration of the atrial action potential at any test temperature but
      lengthened the ventricular action potential by ~17%.

PMID- 22471807
TI  - Early life migration patterns of Baltic Sea pike Esox lucius.
AB  - This study investigated the movement patterns of Baltic Sea pike Esox lucius in
      Matsalu Bay, Estonia, using otolith microchemistry. Migration patterns of E.
      lucius were remarkably diverse, but distinct groups were evident. Of the E.
      lucius analysed (n = 28), 82% hatched in fresh water and 74% of them left this
      biotope during the first growth season.

PMID- 22471810
TI  - Maternal and neonatal outcomes of large for gestational age pregnancies.
AB  - OBJECTIVE: To compare maternal and neonatal outcomes of term large for
      gestational age (LGA) pregnancies and adequate for gestational age (AGA)
      pregnancies. DESIGN: Retrospective analysis. SETTING: Large university research
      medical center. POPULATION: All term singleton LGA (birthweight >= 90th
      percentile) and AGA pregnancies (birthweight 10.1-89.9th percentile) delivering
      between 2004 and 2008. METHODS: Data collected included maternal age, gestational
      age at delivery, mode of delivery, birthweight, fetal sex, and maternal and
      neonatal complications. Birthweight percentiles were determined according to
      locally derived gender-specific birthweight tables. MAIN OUTCOME MEASURES:
      Comparisons between LGA and AGA pregnancies and between LGA 90-94.9th, 95-98.9th
      and >= 99th percentile. RESULTS: The study population comprised 34 685
      pregnancies; 3900 neonates matched the definition of term LGA. Maternal age and
      gestational age at delivery were significantly higher for LGA neonates.
      Significantly more LGA neonates were born by cesarean section, and significantly
      more LGA pregnancies were complicated by postpartum hemorrhage (PPH), shoulder
      dystocia or neonatal hypoglycemia, and had a longer hospitalization period.
      Maternal and neonatal risks increased as birthweight increased from the 90-94.9th
      to 95-98.9th to >= 99th percentile. Specifically, the risks of shoulder dystocia
      (odds ratio 2.61, 3.35 and 5.11, respectively), PPH (odds ratio 1.81, 2.12 and
      3.92, respectively) and neonatal hypoglycemia (odds ratio 2.53, 3.8 and 5.19,
      respectively) all increased linearly with birthweight percentile. CONCLUSIONS:
      Large for gestational age pregnancies are associated with an increased rate of
      cesarean section, PPH, shoulder dystocia and neonatal hypoglycemia, as well as
      longer hospitalization. These risks increase as the birth percentile rises. These
      risks need to be emphasized in pre-delivery counseling.

PMID- 22471811
TI  - Light chain deposition disease: novel biological insights and treatment advances.
AB  - Light chain deposition disease (LCDD) is a monoclonal gammopathy characterized by
      nonamyloid deposition of immunoglobulin light chains in various organs. Most
      cases present with renal dysfunction, a ubiquitous feature of this disease, and
      in some instances, it may progress to end-stage renal disease. Unfortunately,
      until now, no standard treatment has been established. The use of alkylating
      agents and steroids has been extensively reported. However, conventional
      chemotherapy response is generally limited with minor effects on kidney function.
      The use of novel agents such as bortezomib has shown a more rapid response with a
      dramatically important reduction of light chains in serum and/or urine in small
      series of cases. Furthermore, autologous stem cell transplantation has been
      reported as a feasible strategy in LCDD, able to prolong the dialysis-free
      survival. Nonetheless, toxicity from these therapies should be considered
      carefully because most of patients might present with kidney dysfunction that
      could limit the use of some agents.

PMID- 22471812
TI  - Gene structure and expression of serotonin receptor HTR2C in hypothalamic samples
      from infanticidal and control sows.
AB  - BACKGROUND: The serotonin pathways have been implicated in behavioural phenotypes
      in a number of species, including human, rat, mouse, dog and chicken. Components
      of the pathways, including the receptors, are major targets for drugs used to
      treat a variety of physiological and psychiatric conditions in humans. In our
      previous studies we have identified genetic loci potentially contributing to
      maternal infanticide in pigs, which includes a locus on the porcine X chromosome
      long arm. The serotonin receptor HTR2C maps to this region, and is therefore an
      attractive candidate for further study based on its function and its position in
      the genome. RESULTS: In this paper we describe the structure of the major
      transcripts produced from the porcine HTR2C locus using cDNA prepared from
      porcine hypothalamic and pooled total brain samples. We have confirmed
      conservation of sites altered by RNA editing in other mammalian species, and
      identified polymorphisms in the gene sequence. Finally, we have analysed
      expression and editing of HTR2C in hypothalamus samples from infanticidal and
      control animals. CONCLUSIONS: The results confirm that although the expression of
      the long transcriptional variant of HTR2C is raised in infanticidal animals, the
      overall patterns of editing in the hypothalamus are similar between the two
      states.Sequences associated with the cDNA and genomic structures of HTR2C
      reported in this paper are deposited in GenBank under accession numbers FR720593,
      FR720594 and FR744452.

PMID- 22471813
TI  - Sources of emotional maltreatment and the differential development of
      unconditional and conditional schemas.
AB  - Schema theory posits that experiences of maltreatment result in the early
      development of maladaptive schemas (EMS; Young, Klosko, & Weishaar, 2003, Schema
      therapy: A practitioner's guide, The Guilford Press: New York, NY). EMS are
      organized by conditionality; unconditional schemas are theorized to develop early
      in childhood predominantly in response to experiences of parenting and
      conditional schemas are theorized to develop later in life in response to other
      relationships. Despite this distinction, minimal previous research has
      investigated their differential development. The current study examined the
      relative contributions of parental and other (peer and intimate partner)
      emotional maltreatment (EMT) in the differential development of unconditional and
      conditional schemas. Ninety-seven undergraduate students retrospectively reported
      their maltreatment experiences using the Lifetime Experiences Questionnaire and
      completed the Young Schema Questionnaire to measure EMS. Consistent with
      hypotheses, parental EMT was the strongest predictor of unconditional schemas.
      Unexpectedly, parental EMT also emerged as the strongest predictor of conditional
      schemas. Theoretical and clinical implications of these findings are discussed.

PMID- 22471814
TI  - Peripheral blood cytopaenia limiting initiation of treatment in chronic hepatitis
      C patients otherwise eligible for antiviral therapy.
AB  - BACKGROUND: In patients with chronic hepatitis C virus (HCV) infection, the
      presence of peripheral blood cytopaenia may represent an obstacle to pegylated
      interferon and ribavirin treatment. AIMS: To evaluate the prevalence of anaemia,
      neutropaenia and thrombocytopaenia potentially limiting initiation of pegylated
      interferon and ribavirin treatment in patients with chronic HCV infection who
      were otherwise eligible for antiviral therapy. METHODS: We studied 3059
      consecutive anti-HCV and HCV-RNA positive patients referred to our centre to be
      evaluated for antiviral therapy from June 2002 to May 2011. The European
      Association for the Study of Liver HCV guidelines were applied to assess
      eligibility for antiviral therapy. RESULTS: In the study cohort, 1,521 patients
      (49.7%) were not eligible for treatment because of reasons different from
      haematological abnormalities. In the remaining 1,538 patients the overall
      prevalence of any peripheral blood cytopaenia potentially preventing patients
      from being treated with antiviral therapy was 15.1%. In particular, anaemia
      (haemoglobin level < 12 g/dL for women, <13 g/dL for men) was a relative
      contraindication to treatment in 8.9% (137/1,538) of the patients, while
      thrombocytopaenia (platelet count cut-off, 90 * 10(9) /L) and neutropaenia
      (absolute neutrophil count < 1.5 * 10(9) /L) limited treatment in 6.5% (100/1358)
      and 3.2% (48/1358) of patients respectively. These haematological abnormalities
      were more prevalent in patients with older age (P < 0.004) and cirrhosis (P <
      0.001). CONCLUSIONS: The presence of peripheral blood cytopaenia may potentially
      limit initiation of antiviral therapy in one in every seven patients with chronic
      HCV infection who are otherwise eligible for treatment.

PMID- 22471815
TI  - Porphyromonas gingivalis infection at different gestation periods on fetus
      development and cytokines profile.
AB  - AIM: Infective agents may affect pregnancy outcomes by deregulating homeostasis.
      OBJECTIVES: The effects of Porphyromonas gingivalis infection before and at
      different gestation periods were evaluated. MATERIALS AND METHODS: Wistar rats
      infected via subcutaneous with P. gingivalis W83, one week before mating (BM),
      days 1 (PR1) and 11 of gestation (PR11), and controls were evaluated, and samples
      were obtained at the end of gestation. P. gingivalis was detected by PCR.
      Cytokine was determined by ELISA. RESULTS: Infected rats had lower maternal gain
      of weight. Implantation was not observed in 2/12 BM rats. PR11 presented more
      fetal-placental resorptions and lower placenta/fetus weight than controls. P.
      gingivalis was detected in placenta and fetus. IL-6 and TNF-alpha levels were
      higher in placenta and serum of infected groups, except for TNF-alpha in placenta
      of PR1. IL-1beta levels were higher in placenta of PR11, but lower in serum and
      placenta of PR1. There were no differences in IL-10 and PGE2 concentrations among
      the groups (P < 0.05). CONCLUSIONS: The experimental infection by P. gingivalis
      resulted in alterations in the gestational pattern and in fetal development. The
      consequences of infection at mid-gestation were more severe than at the
      beginning, possibly due to the induction of pro-inflammatory cytokines in the
      fetal compartment.

PMID- 22471816
TI  - Biocompatible and biodegradable dual-drug release system based on silk hydrogel
      containing silk nanoparticles.
AB  - We developed a facile and quick ethanol-based method for preparing silk
      nanoparticles and then fabricated a biodegradable and biocompatible dual-drug
      release system based on silk nanoparticles and the molecular networks of silk
      hydrogels. Model drugs incorporated in the silk nanoparticles and silk hydrogels
      showed fast and constant release, respectively, indicating successful dual-drug
      release from silk hydrogel containing silk nanoparticles. The release behaviors
      achieved by this dual-drug release system suggest to be regulated by physical
      properties (e.g., beta-sheet contents and size of the silk nanoparticles and
      network size of the silk hydrogels), which is an important advantage for
      biomedical applications. The present silk-based system for dual-drug release also
      demonstrated no significant cytotoxicity against human mesenchymal stem cells
      (hMSCs), and thus, this silk-based dual-drug release system has potential as a
      versatile and useful new platform of polymeric materials for various types of
      dual delivery of bioactive molecules.

PMID- 22471820
TI  - A call for internship quality control.

PMID- 22471821
TI  - What is your diagnosis? Infection with dimorphic Blastomyces dermatitidis.

PMID- 22471822
TI  - Diagnostic imaging in veterinary dental practice. Incomplete formation of the
      apical infundibula of the permanent right maxillary second premolar tooth.

PMID- 22471823
TI  - Pathology in practice. Microsporum gypseum infection.

PMID- 22471824
TI  - Pathology in practice. Leptospirosis.

PMID- 22471825
TI  - Comparison of arterial blood pressure measurements and hypertension scores
      obtained by use of three indirect measurement devices in hospitalized dogs.
AB  - OBJECTIVE: To evaluate the agreement of blood pressure measurements and
      hypertension scores obtained by use of 3 indirect arterial blood pressure
      measurement devices in hospitalized dogs. Design-Diagnostic test evaluation.
      ANIMALS: 29 client-owned dogs. PROCEDURES: 5 to 7 consecutive blood pressure
      readings were obtained from each dog on each of 3 occasions with a Doppler
      ultrasonic flow detector, a standard oscillometric device (STO), and a high
      definition oscillometric device (HDO). RESULTS: When the individual sets of 5 to
      7 readings were evaluated, the coefficient of variation for systolic arterial
      blood pressure (SAP) exceeded 20% for 0% (Doppler), 11 % (STO), and 28% (HDO) of
      the sets of readings. After readings that exceeded a 20% coefficient of variation
      were discarded, repeatability was within 25 (Doppler), 37 (STO), and 39 (HDO) mm
      Hg for SAP. Correlation of mean values among the devices was between 0.47 and
      0.63. Compared with Doppler readings, STO underestimated and HDO overestimated
      SAP. Limits of agreement between mean readings of any 2 devices were wide. With
      the hypertension scale used to score SAP, the intraclass correlation of scores
      was 0.48. Linear-weighted inter-rater reliability between scores was 0.40
      (Doppler vs STO), 0.38 (Doppler vs HDO), and 0.29 (STO vs HDO). CONCLUSIONS AND
      CLINICAL RELEVANCE: Results of this study suggested that no meaningful clinical
      comparison can be made between blood pressure readings obtained from the same dog
      with different indirect blood pressure measurement devices.

PMID- 22471826
TI  - Accuracy, intermethod agreement, and inter-reviewer agreement for use of magnetic
      resonance imaging and myelography in small-breed dogs with naturally occurring
      first-time intervertebral disk extrusion.
AB  - OBJECTIVE: To determine accuracy, intermethod agreement, and inter-reviewer
      agreement for multisequence magnetic resonance imaging (MRI) and 2-view
      orthogonal myelography in small-breed dogs with first-time intervertebral disk
      (IVD) extrusion. DESIGN: Prospective evaluation study. ANIMALS: 24 dogs with
      thoracolumbar IVD extrusion. PROCEDURES: Each dog underwent MRI and myelography.
      Images obtained with each modality were independently evaluated and assigned
      standardized scores in a blinded manner by 3 reviewers. Results were compared
      with surgical findings. Inter-reviewer and intermethod agreements were assessed
      via kappa statistics. Accuracy was assessed as the percentage of dogs for which
      >= 2 of 3 reviewers recorded findings identical to those determined surgically.
      RESULTS: Inter-reviewer agreement was substantial for site (kappa = 0.70) and
      side of IVD extrusion (kappa = 0.62) in T2-weighted magnetic resonance images and
      was substantial for site (kappa = 0.72) and fair for side of extrusion (kappa =
      0.37) in myelographic images. Agreement for site between each modality and
      surgical findings was near perfect (kappa = 0.94 and 0.88 for MRI and
      myelography, respectively). Intermethod agreement was substantial for site (kappa
      = 0.71) and moderate for side of extrusion (kappa = 0.40). Accuracy of MRI for
      site and side was 100% when results for T1-weighted, T2-weighted, and contrast
      enhanced T1-weighted sequences were combined. Accuracy of myelography was 90.9%
      and 54.5% for site and side, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      Agreement between imaging results and surgical findings for identification of IVD
      extrusion sites in small-breed dogs was similar for MRI and myelography. However,
      MRI appeared to be more accurate than myelography and allowed evaluation of
      extradural compressive mass composition.

PMID- 22471827
TI  - Transdiaphragmatic extension of a retroperitoneal lipoma into the intrathoracic
      extrapleural space via the lumbocostal trigone in a dog.
AB  - CASE DESCRIPTION: An 8-year-old 12.2-kg (26.9-lb) spayed female American Cocker
      Spaniel was referred for evaluation of abdominal discomfort and a suspected intra
      abdominal lipoma with possible invasion into the thorax. CLINICAL FINDINGS:
      Physical examination revealed a tense abdomen, and the margins of a large
      abdominal mass could be appreciated. Abdominal imaging revealed a mass of fat
      opacity in the abdominal and thoracic cavities. Computed tomography with
      precontrast and postcontrast peritoneograms was used to determine whether the
      masses connected via a diaphragmatic defect. TREATMENT AND OUTCOME: Exploratory
      laparotomy revealed a retroperitoneal lipomatous mass that had focally invaded
      the hypaxial musculature and had extended across the dorsolateral aspect of the
      diaphragm via the lumbocostal trigone into the intrathoracic extrapleural space.
      Surgical resection required transdiaphragmatic thoracotomy. Histologic
      examination of excised tissue confirmed the preoperative diagnosis of a lipoma.
      The dog recovered from surgery with no complications and had no disease
      recurrence for at least 32 months after surgical resection. CLINICAL RELEVANCE:
      The defect of the lumbocostal trigone is also called the foramen of Bochdalek in
      humans, and it is recognized as a common location for congenital diaphragmatic
      hernia. A lumbocostal trigone hernia may be considered as a differential
      diagnosis for bicavitary masses in dogs, particularly in the absence of a history
      of trauma.

PMID- 22471828
TI  - Endoscopic placement of ureteral stents for treatment of congenital bilateral
      ureteral stenosis in a dog.
AB  - CASE DESCRIPTION: A 5-year-old 8.6-kg (18.9-lb) spayed female Pug was evaluated
      because of chronic hematuria and recurrent urinary tract infections. CLINICAL
      FINDINGS: Excretory urography, ultrasonography, and excretory CT urography were
      performed. Results indicated that the dog had bilateral hydronephrosis and
      hydroureter and suspected proximal ureteral stenosis. Retrograde
      ureteropyelography confirmed the presence of stenosis at the ureteropelvic
      junction of each ureter, along with a large amount of endoluminal ureteral
      debris. Clinical findings suggested that the dog had a congenital bilateral
      anomaly of the upper urinary tract. TREATMENT AND OUTCOME: The dog was
      anesthetized, and 2 double-pigtail ureteral stents were placed cystoscopically
      with fluoroscopic guidance for immediate relief of the ureteropelvic junction
      obstructions. Each stent extended from the left or right renal pelvis to the
      urinary bladder. The procedures and the patient's recovery from anesthesia were
      uncomplicated. Continuing improvements in severity of hydronephrosis,
      hydroureter, and dysuria were evident during routine follow-up examinations at 2,
      4, 12, 16, and 45 weeks after stent placement. Over the subsequent 12 months, all
      clinical signs remained resolved other than a urinary tract infection that was
      successfully treated with antimicrobials. CLINICAL RELEVANCE: Ureteral stenosis
      should be considered as a differential diagnosis for hydronephrosis in dogs,
      particularly when urinary tract calculi or neoplasia is not present. Chronic
      hematuria and recurrent urinary tract infections can be associated with this
      condition. Placement of ureteral stents may be a successful treatment option for
      ameliorization of congenital ureteral obstructions.

PMID- 22471829
TI  - Comparison of the effects of xylazine bolus versus medetomidine constant rate
      infusion on cardiopulmonary function and depth of anesthesia in horses
      anesthetized with isoflurane.
AB  - OBJECTIVE: To compare the effects of xylazine bolus versus medetomidine constant
      rate infusion (MCRI) on cardiopulmonary function and depth of anesthesia in
      dorsally recumbent, spontaneously breathing, isoflurane-anesthetized horses.
      DESIGN: Prospective, randomized crossover study. ANIMALS: 10 healthy adult
      Standardbreds. PROCEDURES: Horses were premedicated with xylazine or medetomidine
      IV. Anesthesia was induced with diazepam and ketamine and maintained with
      isoflurane for 150 minutes. For the xylazine treatment, end-tidal isoflurane
      concentration was maintained at 1.7%, and xylazine (0.2 mg/kg [0.09 mg/lb], IV)
      was administered as a bolus at the end of anesthesia. For the MCRI treatment, end
      tidal isoflurane concentration was maintained at 1.4%, and medetomidine (0.005
      mg/kg/h [0.0023 mg/lb/h], IV) was infused throughout anesthesia. Physiologic data
      (ie, heart rate, respiratory rate, rectal temperature, bispectral index, and
      electromyographic values) were compared between treatments with xylazine bolus
      versus MCRI. RESULTS: Heart rate was lower, but mean arterial blood pressure was
      higher from 20 to 40 minutes with MCRI treatment, compared with conventional
      treatment with xylazine. Respiratory rate and rectal temperature were greater
      with MCRI treatment. Bispectral index was lower with MCRI treatment from 80 to
      150 minutes, and electromyographic values were lower with MCRI treatment from 30
      to 150 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized
      horses, premedication with medetomidine followed by administration of
      medetomidine as a constant rate infusion resulted in decreased heart rate, higher
      arterial blood pressure from 20 through 40 minutes after induction of anesthesia,
      and better preserved body temperature, compared with conventional treatment with
      xylazine. Greater depth of anesthesia and muscle relaxation were seen with MCRI
      treatment, despite the lower isoflurane concentration.

PMID- 22471830
TI  - Comparison of the effects of xylazine bolus versus medetomidine constant rate
      infusion on the stress response, urine production, and anesthetic recovery
      characteristics in horses anesthetized with isoflurane.
AB  - OBJECTIVE: To compare the effect of xylazine bolus versus medetomidine constant
      rate infusion (MCRI) on serum cortisol and glucose concentrations, urine
      production, and anesthetic recovery characteristics in dorsally recumbent,
      spontaneously breathing, isoflurane-anesthetized horses. DESIGN: Prospective,
      randomized crossover study. ANIMALS: 10 healthy Standardbreds. PROCEDURES: Horses
      were premedicated with xylazine or medetomidine IV. Anesthesia was induced with
      diazepam and ketamine and maintained with isoflurane for 150 minutes. For the
      xylazine treatment, end-tidal isoflurane concentration was maintained at 1.7% and
      xylazine (0.2 mg/kg [0.09 mg/lb]), IV) was administered as a bolus at the end of
      anesthesia. For the MCRI treatment, end-tidal isoflurane concentration was
      maintained at 1.4% and medetomidine (0.005 mg/kg/h [0.0023 mg/lb/h], IV) was
      infused throughout anesthesia. Serum cortisol and glucose concentrations were
      measured before, during, and after anesthesia. Urine specific gravity and volume
      were measured during anesthesia. Unassisted anesthetic recoveries were recorded
      by a digital video camera for later evaluation by 2 observers who were blinded to
      treatment. RESULTS: Serum cortisol concentration was lower and serum glucose
      concentration was higher with MCRI treatment, compared with xylazine treatment.
      Time to sternal recumbency was longer with MCRI treatment, but no difference was
      seen between treatments for times to extubation, first movement, or standing.
      Objective (mean attempt interval) and subjective (visual analog score) recovery
      scores were significantly better with MCRI treatment, compared with xylazine
      treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized horses,
      premedication and administration of medetomidine as a constant rate infusion
      resulted in decreased serum cortisol concentration, increased serum glucose
      concentration, and superior anesthetic recovery characteristics, compared with
      conventional treatment with xylazine.

PMID- 22471831
TI  - Evaluation of the use of nonesterified fatty acids and beta-hydroxybutyrate
      concentrations in pooled serum samples for herd-based detection of subclinical
      ketosis in dairy cows during the first week after parturition.
AB  - OBJECTIVE: To evaluate the use of nonesterified fatty acids (NEFA) and beta
      hydroxybutyrate (BHBA) concentrations in pooled serum samples for herd-based
      detection of subclinical ketosis (SCK) in dairy cows after calving. DESIGN: Cross
      sectional study. ANIMALS: 1,100 dairy cows from 110 herds. PROCEDURES: Blood
      samples were collected from 10 healthy cows/herd in the first week after
      parturition. Aliquots of serum were mixed to create a pooled sample.
      Concentrations of NEFA and BHBA were measured to estimate prevalence of SCK.
      Pooled sample test results were compared with those obtained for individual
      samples. Linear regression and receiver-operating characteristic curve analysis
      were performed; Bland-Altman plots were used to evaluate agreement between
      methods. RESULTS: Overall prevalence of SCK was 30.7%, 19.3%, and 13.6%, as
      determined by use of BHBA threshold concentrations of 1,000, 1,200, and 1,400
      MUmol/L, respectively. Pooled sample concentrations of NEFA and BHBA were
      significantly correlated (r = 0.98 and 0.97, respectively) with individual sample
      means and with the number of cows that had NEFA (R(2) range, 0.81 to 0.84) or
      BHBA (R(2) range, 0.65 to 0.76) concentrations above predefined thresholds.
      Pooled sample concentrations of NEFA and BHBA were very accurate to highly
      accurate for herd-based detection of SCK. CONCLUSIONS AND CLINICAL RELEVANCE:
      Analysis of NEFA and BHBA concentrations in pooled serum samples was useful for
      herd-based detection of SCK. A sample size of 10 cows/herd was deemed adequate
      for monitoring dairy herds for SCK. Reference criteria specific to pooled samples
      should be used for this type of herd-based testing.

PMID- 22471832
TI  - A novel X-chromosomal microdeletion encompassing congenital hemidysplasia with
      ichthyosiform erythroderma and limb defects.
AB  - We report an unusual phenotype of congenital hemidysplasia with ichthyosiform
      erythroderma and limb defects syndrome most likely resulting from a novel X
      chromosomal microdeletion encompassing the promoter region and exon 1 of the
      nicotinamide adenine dinucleotide phosphate steroid dehydrogenase-like protein
      gene, the neighboring gene CETN2, and more than 10 kb of noncoding
      deoxyribonucleic acid.

PMID- 22471834
TI  - Computed tomographic assessment of maxillary sinus wall thickness in edentulous
      patients.
AB  - Posterior maxillary region is considered to be the most challenging area for
      dental implant placement. Lateral window opening is the gold standard procedure
      for maxillary sinus augmentation in this area. The purpose of this study is to
      evaluate lateral wall thickness of the maxillary sinus for sinus augmentation
      using computed tomography (CT) in edentulous patients. Computed tomography images
      of 302 patients were analysed. Using the maxillary sinus floor as the reference
      point in edentulous regions, lateral wall thickness was measured on CT scans.
      After drawing a tangent line at the lowest point of the sinus floor, another
      perpendicular line to the tangent line was drawn at the same point of the sinus
      floor. Thickness of the lateral wall of the maxillary sinus was measured using
      10DR implant software at 3 (R1), 10 (R2) and 15 mm (R3) from the sinus floor. The
      mean thickness of the lateral wall of the maxillary sinus from the first premolar
      to second molar was 1.69 +/- 0.71, 1.50 +/- 0.72, 1.77 +/- 0.78 and 1.89 +/- 0.85
      mm, respectively. The thickness differed significantly at the R2 and R3 points.
      Women had thinner lateral walls at the R1 and R2 points at the premolars than did
      men. At the R2 and R3 points at the second premolar, the mean thickness of
      smokers was larger than that of non-smokers. There were no significant
      differences on age or reasons for tooth loss. The changes in the thickness of the
      lateral wall at different reference points were observed, and CT examinations may
      help make lateral window without membrane perforation.

PMID- 22471833
TI  - Experimental and theoretical studies on the Nazarov cyclization/Wagner-Meerwein
      rearrangement sequence.
AB  - Highly functionalized cyclopentenones can be generated by a chemoselective
      copper(II)-mediated Nazarov/Wagner-Meerwein rearrangement sequence of divinyl
      ketones. A detailed investigation of this sequence is described including a study
      of substrate scope and limitations. After the initial 4pi electrocyclization,
      this reaction proceeds via two different sequential [1,2]-shifts, with
      selectivity that depends upon either migratory ability or the steric bulkiness of
      the substituents at C1 and C5. This methodology allows the creation of vicinal
      stereogenic centers, including adjacent quaternary centers. This sequence can
      also be achieved by using a catalytic amount of copper(II) in combination with
      NaBAr(4)(f), a weak Lewis acid. During the study of the scope of the reaction, a
      partial or complete E/Z isomerization of the enone moiety was observed in some
      cases prior to the cyclization, which resulted in a mixture of diastereomeric
      products. Use of a Cu(II)-bisoxazoline complex prevented the isomerization,
      allowing high diastereoselectivity to be obtained in all substrate types. In
      addition, the reaction sequence was studied by DFT computations at the UB3LYP/6
      31G(d,p) level, which are consistent with the proposed sequences observed,
      including E/Z isomerizations and chemoselective Wagner-Meerwein shifts.

PMID- 22471835
TI  - Role of propolis on tyrosine hydroxylase activity and blood pressure in nitric
      oxide synthase-inhibited hypertensive rats.
AB  - Reduction in the synthesis or bioavailability of nitric oxide plays a significant
      role in the development of hypertension. Propolis is a resinous product collected
      by honeybees from various plant sources. Tyrosine hydroxylase (TH) is the rate
      limiting enzyme in the biosynthesis of catecholamines. The aim of this study was
      to examine the effect of propolis on blood pressure (BP), TH, and total RNA
      levels in the adrenal medulla, heart, and hypothalamus tissues in chronic nitric
      oxide synthase (NOS)-inhibited rats by N(w)-nitro-l-arginine methyl ester (L
      NAME). Rats received NOS inhibitor (L-NAME) for 15 days to produce hypertension
      and propolis for the last 5 days. TH activity and total RNA levels significantly
      increased in adrenal medulla, heart, and hypothalamus tissues in L-NAME-treated
      groups (P < .05). TH activity and total RNA levels of L-NAME+propolis-treated
      rats reduced (P < .05) compared with L-NAME-treated groups. TH activity in
      propolis-treated rats was reduced to the control values. L-NAME led to a
      significant increase in BP compared with the control group. Propolis
      administration to L-NAME-treated rats reduced BP but this was not statistically
      significant compared to L-NAME-treated groups. These results suggest that
      propolis decreases TH activity in NOS-inhibited hypertensive rats and thereby may
      modulate the synthesis of catecholamine and BP.

PMID- 22471836
TI  - Errors in medication history at hospital admission: prevalence and predicting
      factors.
AB  - BACKGROUND: An accurate medication list at hospital admission is essential for
      the evaluation and further treatment of patients. The objective of this study was
      to describe the frequency, type and predictors of errors in medication history,
      and to evaluate the extent to which standard care corrects these errors. METHODS:
      A descriptive study was carried out in two medical wards in a Swedish hospital
      using Lund Integrated Medicines Management (LIMM)-based medication
      reconciliation. A clinical pharmacist identified each patient's most accurate pre
      admission medication list by conducting a medication reconciliation process
      shortly after admission. This list was then compared with the patient's
      medication list in the hospital medical records. Addition or withdrawal of a drug
      or changes to the dose or dosage form in the hospital medication list were
      considered medication discrepancies. Medication discrepancies for which no
      clinical reason could be identified (unintentional changes) were considered
      medication history errors. RESULTS: The final study population comprised 670 of
      818 eligible patients. At least one medication history error was identified by
      pharmacists conducting medication reconciliations for 313 of these patients (47%;
      95% CI 43-51%). The most common medication error was an omitted drug, followed by
      a wrong dose. Multivariate logistic regression analysis showed that a higher
      number of drugs at admission (odds ratio [OR] per 1 drug increase = 1.10; 95% CI
      1.06-1.14; p < 0.0001) and the patient living in their own home without any care
      services (OR = 1.58; 95% CI 1.02-2.45; p = 0.042) were predictors for medication
      history errors at admission. The results further indicated that standard care by
      non-pharmacist ward staff had partly corrected the errors in affected patients by
      four days after admission, but a considerable proportion of the errors made in
      the initial medication history at admission remained undetected by standard care
      (OR for medication errors detected by pharmacists' medication reconciliation
      carried out on days 4-11 compared to days 0-1 = 0.52; 95% CI 0.30-0.91; p=0.021).
      CONCLUSIONS: Clinical pharmacists conducting LIMM-based medication
      reconciliations have a high potential for correcting errors in medication history
      for all patients. In an older Swedish population, those prescribed many drugs
      seem to benefit most from admission medication reconciliation.

PMID- 22471838
TI  - Chiroptical effects in planar achiral plasmonic oriented nanohole arrays.
AB  - Chiroptical effects are routinely observed in three dimensional objects lacking
      mirror symmetry or quasi-two-dimensional thin films lacking in-plane mirror
      symmetry. Here we show that symmetric plasmonic planar arrays of circular
      nanoholes produced strong chiroptical responses at visible wavelengths on tilting
      them with respect to the incident light beam due to the collective asymmetric
      nature of their surface plasmon excitations. This extrinsic chiroptical effect
      can be stronger than the local chiroptical response in arrays of intrinsically
      chiral nanoholes and may be useful for chiral sensing and negative refraction.

PMID- 22471839
TI  - Theoretical investigation of interaction of dicarboxylic acids with common
      aerosol nucleation precursors.
AB  - Dicarboxylic acids are important products from photooxidation of volatile organic
      compounds and are believed to play an important role in the formation and growth
      of atmospheric secondary organic aerosols. In this paper, the interaction of five
      dicarboxylic acids, i.e., oxalic acid (C(2)H(2)O(4)), malonic acid
      (C(3)H(4)O(4)), maleic acid (C(4)H(4)O(4)), phthalic acid (C(8)H(6)O(4)), and
      succinic acid (C(4)H(6)O(4)), with sulfuric acid and ammonia has been studied,
      employing quantum chemical calculations, quantum theory of atoms in molecules
      (QTAIM), and the natural bond orbital (NBO) analysis methods. Several levels of
      quantum chemical calculations are considered, including coupled-cluster theory
      with single and double excitations with perturbative corrections for the triple
      excitations (CCSD(T)) and two density functionals, B3LYP and PW91PW91. The free
      energies of formation of the heterodimer and heterotrimer clusters suggest that
      dicarboxylic acids can contribute to the aerosol nucleation process by binding to
      sulfuric acid and ammonia. In particular, the formation energies and structures
      of the heterotrimer clusters show that dicarboxylic acids enhance nucleation in
      two directions, in contrast to monocarboxylic acids.

PMID- 22471837
TI  - Impact of Perinatal Different Intrauterine Environments on Child Growth and
      Development in the First Six Months of Life--IVAPSA Birth Cohort: rationale,
      design, and methods.
AB  - BACKGROUND: In the last twenty years, retrospective studies have shown that
      perinatal events may impact the individual health in the medium and long term.
      However, only a few prospective studies were designed to address this phenomenon.
      This study aims to describe the design and methods of the Impact of Perinatal
      Environmental Variations in the First Six Months of Life - the IVAPSA Birth
      Cohort. METHOD/DESIGN: This is a clinical study and involves the recruitment of a
      birth cohort from hospitals in Porto Alegre, Rio Grande do Sul, Brazil. Mothers
      from different clinical backgrounds (hypertensive, diabetics, smokers, having an
      intrauterine growth restricted child for idiopathic reasons, and controls) will
      be invited to join the study twenty-four hours after the birth of their child.
      Data on economic, social, and maternal health care, feeding practices,
      anthropometric measures, physical activity, and neuropsychological evaluation
      will be obtained in interviews at postpartum, 7 and 15 days, 1, 3 and 6 months of
      life. DISCUSSION: To our knowledge, this is the first thematic cohort focused on
      the effects of intrauterine growth restriction to prospectively enroll mothers
      from different clinical backgrounds. The IVAPSA Birth Cohort is a promising
      research platform that can contribute to the knowledge on the relationship
      between perinatal events and their consequences on the children's early life.

PMID- 22471840
TI  - Cosmetic efficacy evaluation of an anti-acne cream using the 3D image analysis
      system.
AB  - BACKGROUND/PURPOSE: Acne is a skin disease which accompanies pathological and
      morphological changes. Although acne severity is scored by clinicians based on
      pathological status, aesthetic aspect of acne symptom is also concerned by
      patients. This study was conducted to examine the usefulness of a 3D image
      analysis method for the cosmetic efficacy evaluation of an anti-acne cream.
      METHODS: Twenty-one healthy volunteers with acne lesions were recruited for the
      study and treated with an 'anti-acne cream' for 4 weeks. Acne symptoms on the
      facial skin were graded by the visual evaluation of photographs taken before and
      after the treatment. Skin color of acne lesions was and measured by a
      spectrophotometer. In addition, a 3D image analysis system was used to quantify
      skin surface roughness and acne volumes. RESULTS: Both visual and
      spectrophotometric assessments of acne lesions provided similar results
      indicating that the cream treatment improved acne symptoms significantly. The 3D
      image analysis of acne lesions confirmed that the cream treatment decreased skin
      surface roughness and acne volumes. CONCLUSION: The current study demonstrated
      that the 3D image-based analysis of the skin may be useful for the quantification
      of acne symptoms of cosmetic relevance.

PMID- 22471842
TI  - Apolipoproteins a-I and B as components of metabolic syndrome with respect to
      diabetes status: a factor analysis.
AB  - BACKGROUND: The aim of the current study was to elucidate the clustering pattern
      of metabolic syndrome components along with apolipoproteins (Apo) A-I and B in
      diabetic and nondiabetic subjects. METHODS: Factor analysis of conventional
      variables of metabolic syndrome [i.e., waist circumference, homeostasis model
      assessment of insulin resistance (HOMA-IR), triglycerides (TG), high-density
      lipoprotein-cholesterol (HDL-C), and systolic blood pressure (SBP)] with or
      without addition of Apo A-I and B was performed on 567 and 327 diabetic and
      nondiabetic subjects, respectively. Thereafter, analyses were repeated after
      substitution of TG and HDL-C by the TG-to-HDL-C ratio (TG/HDL-C). RESULTS:
      Regarding conventional variables of metabolic syndrome, one or two underlying
      factors were identified, depending on whether lipid measures were entered as two
      distinct variables or as a composite measure. Apolipoproteins were consistent
      with a one-factor structure model of metabolic syndrome and did not change the
      loading pattern remarkably in nondiabetics. TG and HDL-C tended to cluster with
      Apo B and A-I, respectively, in different models. CONCLUSION: The current study
      confirms that addition of Apo A-I and B is consistent with the one-factor model
      of metabolic syndrome and does not modify the loading pattern remarkably in
      nondiabetic subjects.

PMID- 22471841
TI  - Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted
      delivery of antibiotics.
AB  - Bacteria have shown a remarkable ability to overcome drug therapy if there is a
      failure to achieve sustained bactericidal concentration or if there is a
      reduction in activity in situ. The latter can be caused by localized acidity, a
      phenomenon that can occur as a result of the combined actions of bacterial
      metabolism and the host immune response. Nanoparticles (NP) have shown promise in
      treating bacterial infections, but a significant challenge has been to develop
      antibacterial NPs that may be suitable for systemic administration. Herein we
      develop drug-encapsulated, pH-responsive, surface charge-switching poly(D,L
      lactic-co-glycolic acid)-b-poly(L-histidine)-b-poly(ethylene glycol) (PLGA-PLH
      PEG) nanoparticles for treating bacterial infections. These NP drug carriers are
      designed to shield nontarget interactions at pH 7.4 but bind avidly to bacteria
      in acidity, delivering drugs and mitigating in part the loss of drug activity
      with declining pH. The mechanism involves pH-sensitive NP surface charge
      switching, which is achieved by selective protonation of the imidazole groups of
      PLH at low pH. NP binding studies demonstrate pH-sensitive NP binding to bacteria
      with a 3.5 +/- 0.2- to 5.8 +/- 0.1-fold increase in binding to bacteria at pH 6.0
      compared to 7.4. Further, PLGA-PLH-PEG-encapsulated vancomycin demonstrates
      reduced loss of efficacy at low pH, with an increase in minimum inhibitory
      concentration of 1.3-fold as compared to 2.0-fold and 2.3-fold for free and PLGA
      PEG-encapsulated vancomycin, respectively. The PLGA-PLH-PEG NPs described herein
      are a first step toward developing systemically administered drug carriers that
      can target and potentially treat Gram-positive, Gram-negative, or polymicrobial
      infections associated with acidity.

PMID- 22471843
TI  - Masculinities, 'guy talk' and 'manning up': a discourse analysis of how young men
      talk about sexual health.
AB  - Sexually transmitted infection testing rates among young men remain low, and
      their disengagement from sexual health services has been linked to enactments of
      masculinity that prohibit or truncate discussions of sexual health. Understanding
      how men align with multiple masculinities is therefore important for tailoring
      interventions that appropriately respond to their needs. We draw on 32 in-depth
      interviews with 15-24-year-old men to explore the discourses that facilitate or
      shut down sexual health communication with peers and sex partners. We employ a
      critical discourse analysis to explore how men's conversations about sexual
      health are constituted by masculine hierarchies (such as the ways in which
      masculinities influence men's ability to construct or challenge and contest
      dominant discourses about sexual health). Men's conversations about sexual health
      focused primarily around their sexual encounters - something frequently referred
      to as 'guy talk'. Also described were situations whereby participants employed a
      discourse of 'manning up' to (i) exert power over others with disregard for
      potential repercussions and (ii) deploy power to affirm and reify their own hyper
      masculine identities, while using their personal (masculine) power to help others
      (who are subordinate in the social ordering of men). By better understanding how
      masculine discourses are employed by men, their sexual health needs can be
      advanced.

PMID- 22471845
TI  - Addressing the National Academy of Sciences' challenge: a method for statistical
      pattern comparison of striated tool marks.
AB  - In February 2009, the National Academy of Sciences published a report entitled
      "Strengthening Forensic Science in the United States: A Path Forward." The report
      notes research studies must be performed to "...understand the reliability and
      repeatability..." of comparison methods commonly used in forensic science.
      Numerical classification methods have the ability to assign objective
      quantitative measures to these words. In this study, reproducible sets of ideal
      striation patterns were made with nine slotted screwdrivers, encoded into high
      dimensional feature vectors, and subjected to multiple statistical pattern
      recognition methods. The specific methods employed were chosen because of their
      long peer-reviewed track records, widespread successful use for both industry and
      academic applications, rely on few assumptions on the data's underlying
      distribution, can be accompanied by standard confidence levels, and are
      falsifiable. For PLS-DA, correct classification rates of 97% or higher were
      achieved by retaining only eight dimensions (8D) of data. PCA-SVM required even
      fewer dimensions, 4D, for the same level of performance. Finally, for the first
      time in forensic science, it is shown how to use conformal prediction theory to
      compute identifications of striation patterns at a given level of confidence.

PMID- 22471846
TI  - Coinage metals-catalyzed cascade reactions of aryl alkynylaziridines: silver(I)
      single vs gold(I)-double cyclizations.
AB  - Alkynylaziridines carrying an aryl group could be efficiently converted into
      aminoallenylidene isochromans, isoquinolines, or tetrahydronaphtalenes with
      silver(I) salts and into 1-azaspiro[4.5]decane derivatives with gold(I)
      complexes. Mechanistic investigations revealed that both Ag- and Au-catalyzed
      reactions involved a Friedel-Crafts type intramolecular reaction leading to an
      allene and that Au also rapidly promoted a second intramolecular cyclization of
      the aminoallene intermediate to the corresponding spiro derivative.
      Stereochemical investigations suggested an anti-SN(2)'-type pathway for the first
      cyclization leading to a stereodefined allene, which could then be cyclized to
      the corresponding stereodefined spiro product. These results highlight the
      duality between oxo- or azaphilicity and alkynophilicity of Ag and Au as well as
      their complementarity in terms of reactivity.

PMID- 22471847
TI  - The social signal value of emotions.
AB  - Human interactions are replete with emotional exchanges. In these exchanges
      information about the emotional state of the interaction partners is only one
      type of information conveyed. In addition, emotion displays provide information
      about the interaction partners' disposition and the situation as such. That is,
      emotions serve as social signals. Acknowledging this role of emotions, this
      special section brings together research that illustrates how both person
      perception and situational understanding can be derived from emotional displays
      and the modulation of this process through context. Three contributions focus on
      information about expressers and their intentions. An additional article focuses
      on the informative value of emotional expressions for an observer's construal of
      social situations and another article exemplifies the way context determines the
      social impact of emotions. Finally, the last article presents the dynamic nature
      of mutual influence of emotions. In an attempt to integrate these contributions
      and offer lenses for future research, this editorial offers a contextualised
      model of social perception which attempts to systematise not only the types of
      information that emotion expressions can convey, but also to elaborate the notion
      of context.

PMID- 22471848
TI  - Status signals: adaptive benefits of displaying and observing the nonverbal
      expressions of pride and shame.
AB  - A growing body of research suggests that pride and shame are associated with
      distinct, cross-culturally recognised nonverbal expressions, which are
      spontaneously displayed in situations of success and failure, respectively. Here,
      we review these findings, then offer a theoretical account of the adaptive
      benefits of these displays. We argue that both pride and shame expressions
      function as social signals that benefit both observers and expressers.
      Specifically, pride displays function to signal high status, which benefits
      displayers by according them deference from others, and benefits observers by
      affording them valuable information about social-learning opportunities. Shame
      displays function to appease others after a social transgression, which benefits
      displayers by allowing them to avoid punishment and negative appraisals, and
      observers by easing their identification of committed group members and
      followers.

PMID- 22471849
TI  - When feeling bad makes you look good: guilt, shame, and person perception.
AB  - In two studies, we examined how expressions of guilt and shame affected person
      perception. In the first study, participants read an autobiographical vignette in
      which the writer did something wrong and reported feeling either guilt, shame, or
      no emotion. The participants then rated the writer's motivations, beliefs, and
      traits, as well as their own feelings toward the writer. The person expressing
      feelings of guilt or shame was perceived more positively on a number of
      attributes, including moral motivation and social attunement, than the person who
      reported feeling no emotion. In the second study, the writer of the vignette
      reported experiencing (or not experiencing) cognitive and motivational aspects of
      guilt or shame. Expressing a desire to apologise (guilt) or feelings of
      worthlessness (private shame) resulted in more positive impressions than did
      reputational concerns (public shame) or a lack of any of these feelings. Our
      results indicate that verbal expressions of moral emotions such as guilt and
      shame influence perception of moral character as well as likeability.

PMID- 22471850
TI  - Emotion in the neutral face: a mechanism for impression formation?
AB  - The current work examined contributions of emotion-resembling facial cues to
      impression formation. There exist common facial cues that make people look
      emotional, male or female, and from which we derive personality inferences. We
      first conducted a Pilot Study to assess these effects. We found that neutral
      female versus neutral male faces were rated as more submissive, affiliative,
      naive, honest, cooperative, babyish, fearful, happy, and less angry than neutral
      male faces. In our Primary Study, we then "warped" these same neutral faces over
      their corresponding anger and fear displays so the resultant facial appearance
      cues now structurally resembled emotion while retaining a neutral visage (e.g.,
      no wrinkles, furrows, creases, etc.). The gender effects found in the Pilot Study
      were replicated in the Primary Study, suggesting clear stereotype-driven
      impressions. Critically, ratings of the neutral-over-fear warps versus neutral
      over-anger warps also revealed a profile similar to the gender-based ratings,
      revealing perceptually driven impressions directly attributable to emotion
      overgeneralisation.

PMID- 22471851
TI  - Emotion and the construal of social situations: inferences of cooperation versus
      competition from expressions of anger, happiness, and disappointment.
AB  - The notion that emotional expressions regulate social life by providing
      information is gaining popularity. Prior research on the effects of emotional
      expressions on observers' inferential processes has focused mostly on inferences
      regarding the personality traits of the expresser, such as dominance and
      affiliation. We extend this line of research by exploring the possibility that
      emotional expressions shape observers' construal of social situations. Across
      three vignette studies, an interaction partner's expressions of anger, compared
      to expressions of happiness or disappointment, led observers to construe
      hypothetical situations as less cooperative, both in dyads and groups. These
      effects occurred even when factual information regarding the cooperativeness or
      competitiveness of the situation was provided, attesting to the power of
      emotional expressions in shaping the construal of social situations. Results are
      discussed in relation to appraisal theory, reverse appraisals, emotions as social
      information theory, and the emergence of cooperation in groups and cultures.

PMID- 22471852
TI  - Worry spreads: interpersonal transfer of problem-related anxiety.
AB  - This paper distinguishes processes potentially contributing to interpersonal
      anxiety transfer, including object-directed social appraisal, empathic worry, and
      anxiety contagion, and reviews evidence for their operation. We argue that these
      anxiety-transfer processes may be exploited strategically when attempting to
      regulate relationship partners' emotion. More generally, anxiety may serve as
      either a warning signal to other people about threat (alerting function) or an
      appeal for emotional support or practical help (comfort-seeking function).
      Tensions between these two interpersonal functions may account for mutually
      incongruent interpersonal responses to expressed anxiety, including mistargeted
      interpersonal regulation attempts. Because worry waxes and wanes over time as a
      function of other people's ongoing reactions, interpersonal interventions may
      help to alleviate some of its maladaptive consequences.

PMID- 22471853
TI  - Emotional signals in nonverbal interaction: dyadic facilitation and convergence
      in expressions, appraisals, and feelings.
AB  - We examined social facilitation and emotional convergence in amusement, sadness,
      and fear in dynamic interactions. Dyads of friends or strangers jointly watched
      emotion-eliciting films while they either could or could not communicate
      nonverbally. We assessed three components of each emotion (expressions,
      appraisals, and feelings), as well as attention to and social motives toward the
      co-participant. In Study 1, participants interacted through a mute
      videoconference. In Study 2, they sat next to each other and either were or were
      not separated by a partition. Results revealed that facilitation and convergence
      are not uniform across different emotions and emotion components. Particularly
      strong supporting patterns emerged for the facilitation of and convergence in
      smiling. When direct interaction was possible (Study 2), friends showed a general
      tendency for strong convergence, with the exception of fear-related appraisals.
      This suggests that underlying processes of emotional contagion and social
      appraisal are differentially relevant for different emotions.

PMID- 22471854
TI  - Podoplanin expression in oral leukoplakia: prognostic value and
      clinicopathological implications.
AB  - OBJECTIVES: Current clinicopathological parameters cannot predict the risk of
      malignant transformation in oral leukoplakia sufficiently. Recent studies have
      shown that podoplanin is expressed in oral cancer and precancerous lesions. The
      aim of our study was to assess whether podoplanin expression in pretreatment
      biopsies could serve as a biomarker to predict the risk of malignant
      transformation in patients with oral leukoplakia. MATERIALS AND METHODS: In this
      retrospective study, podoplanin expression was analysed in 60 patients with
      previously untreated oral leukoplakia by immunohistochemistry. We investigated
      the associations between podoplanin expression and various clinicopathological
      variables including oral cancer-free survival (OCFS) and the SIN-classification.
      RESULTS: The chi-square-test revealed that high expression of podoplanin in
      pretreatment biopsies was associated with malignant transformation (P = 0.003)
      and increasing SIN-classification (P = 0.009). In univariate analysis, podoplanin
      expression in oral leukoplakia had a significant impact on OCFS (P = 0.009). The
      5-year OCFS rate decreased from 100% for patients with no podoplanin expression
      to 41.7% for patients with the highest level of podoplanin expression.
      CONCLUSION: Although podoplanin expression and the SIN-classification served as
      factors to predict malignant transformation in patients with oral leukoplakia in
      univariate analysis, no significant impact was found for both factors in
      multivariate analysis.

PMID- 22471856
TI  - Telomere length in circulating serum DNA as a novel non-invasive biomarker for
      cirrhosis: a nested case-control analysis.
AB  - BACKGROUND & AIMS: Previous studies have indicated that telomere length is
      associated with altered risk of various tumours including hepatitis B virus (HBV)
      related hepatocellular carcinoma. However, the association between telomere
      length and the risk of cirrhosis has not been reported. METHODS: In this nested
      case-control study, we used real-time quantitative PCR to determine the relative
      telomere length (RTL) in serum DNA samples from 100 HBV-related cirrhosis cases
      and 100 frequency-matched HBV controls, and evaluated the associations between
      RTL and cirrhosis risk by logistic regression analyses. RESULTS: We found that
      cirrhotic cases had a significantly longer RTL (median, 0.36; range, 0.08-1.87)
      than non-cirrhotic controls (median, 0.20; range, 0.05-1.11) (P < 0.0001).
      Compared with subjects with short RTL, those with long RTL had a significantly
      increased cirrhosis risk [odds ratio, 2.76, 95% confidence interval, 1.50-5.10; P
      = 0.001]. Quartile analysis further indicated a dose-response effect for this
      association. Compared with patients with the lowest quartile of RTL, the
      cirrhosis risk for those with the second, third and highest quartile of RTL was
      2.68 (0.91-7.87, P = 0.073), 3.37 (1.32-10.54, P = 0.013) and 6.64 (2.41-18.32, P
      < 0.0001) respectively (P(trend) <0.0001). Moreover, the area under the receiver
      operating characteristic curve increased from 0.60 (epidemiological variables) to
      0.72 (epidemiological variables plus RTL), with statistically significant
      difference assessed by bootstrap analysis. CONCLUSIONS: Our study presents the
      first epidemiological evidence that RTL in serum DNA could potentially be used as
      a simple, inexpensive and non-invasive marker of cirrhosis risk, a finding that
      warrants further investigations in independent retrospective and prospective
      populations.

PMID- 22471857
TI  - A prospective cohort study to evaluate peridomestic infection as a determinant of
      dengue transmission: protocol.
AB  - BACKGROUND: Vector control programs, which have focused mainly on the patient
      house and peridomestic areas around dengue cases, have not produced the expected
      impact on transmission. This project will evaluate the assumption that the
      endemic/epidemic transmission of dengue begins around peridomestic vicinities of
      the primary cases. Its objective is to assess the relationship between
      symptomatic dengue case exposure and peridomestic infection incidence.
      METHODS/DESIGN: A prospective cohort study will be conducted (in Tepalcingo and
      Axochiapan, in the state of Morelos, Mexico), using the state surveillance system
      for the detection of incident cases. Paired blood specimens will be collected
      from both the individuals who live with the incident cases and a sample of
      subjects residing within a 25-meter radius of such cases (exposed cohort), in
      order to measure dengue-specific antibodies. Other subjects will be selected from
      areas which have not presented any incident cases within 200 meters, during the
      two months preceding the sampling (non-exposed cohort). Symptomatic/asymptomatic
      incident infection will be considered as the dependent variable, exposure to
      confirmed dengue cases, as the principal variable, and the socio-demographic,
      environmental and socio-cultural conditions of the subjects, as additional
      explanatory variables. DISCUSSION: Results indicating a high infection rate among
      the exposed subjects would justify the application of peridomestic control
      measures and call for an evaluation of alternate causes for insufficient program
      impact. On the other hand, a low incidence of peridomestic-infected subjects
      would support the hypothesis that infection occurs outside the domicile, and
      would thus explain why the vector control measures applied in the past have
      exerted such a limited impact on cases incidence rates. The results of the
      present study may therefore serve to reassess site selection for interventions of
      this type.

PMID- 22471858
TI  - Steroid-free immunosuppression in teenagers: living without a safety net.

PMID- 22471859
TI  - Generation and analysis of blueberry transcriptome sequences from leaves,
      developing fruit, and flower buds from cold acclimation through deacclimation.
AB  - BACKGROUND: There has been increased consumption of blueberries in recent years
      fueled in part because of their many recognized health benefits. Blueberry fruit
      is very high in anthocyanins, which have been linked to improved night vision,
      prevention of macular degeneration, anti-cancer activity, and reduced risk of
      heart disease. Very few genomic resources have been available for blueberry,
      however. Further development of genomic resources like expressed sequence tags
      (ESTs), molecular markers, and genetic linkage maps could lead to more rapid
      genetic improvement. Marker-assisted selection could be used to combine traits
      for climatic adaptation with fruit and nutritional quality traits. RESULTS:
      Efforts to sequence the transcriptome of the commercial highbush blueberry
      (Vaccinium corymbosum) cultivar Bluecrop and use the sequences to identify genes
      associated with cold acclimation and fruit development and develop SSR markers
      for mapping studies are presented here. Transcriptome sequences were generated
      from blueberry fruit at different stages of development, flower buds at different
      stages of cold acclimation, and leaves by next-generation Roche 454 sequencing.
      Over 600,000 reads were assembled into approximately 15,000 contigs and 124,000
      singletons. The assembled sequences were annotated and functionally mapped to
      Gene Ontology (GO) terms. Frequency of the most abundant sequences in each of the
      libraries was compared across all libraries to identify genes that are
      potentially differentially expressed during cold acclimation and fruit
      development. Real-time PCR was performed to confirm their differential expression
      patterns. Overall, 14 out of 17 of the genes examined had differential expression
      patterns similar to what was predicted from their reads alone. The assembled
      sequences were also mined for SSRs. From these sequences, 15,886 blueberry EST
      SSR loci were identified. Primers were designed from 7,705 of the SSR-containing
      sequences with adequate flanking sequence. One hundred primer pairs were tested
      for amplification and polymorphism among parents of two blueberry populations
      currently being used for genetic linkage map construction. The tetraploid mapping
      population was based on a cross between the highbush cultivars Draper and Jewel
      (V. darrowii is also in the background of 'Jewel'). The diploid mapping
      population was based on a cross between an F1 hybrid of V. darrowii and diploid
      V. corymbosum and another diploid V. corymbosum. The overall amplification rate
      of the SSR primers was 68% and the polymorphism rate was 43%. CONCLUSIONS: These
      results indicate that this large collection of 454 ESTs will be a valuable
      resource for identifying genes that are potentially differentially expressed and
      play important roles in flower bud development, cold acclimation, chilling unit
      accumulation, and fruit development in blueberry and related species. In
      addition, the ESTs have already proved useful for the development of SSR and EST
      PCR markers, and are currently being used for construction of genetic linkage
      maps in blueberry.

PMID- 22471861
TI  - Adult Changes in Thought study: dementia is an individually varying convergent
      syndrome with prevalent clinically silent diseases that may be modified by some
      commonly used therapeutics.
AB  - The Adult Changes in Thought (ACT) study is a longitudinal population-based
      prospective cohort study of brain aging and incident dementia in the Seattle
      metropolitan area. Observational studies using autopsies from ACT indicate that
      dementia is a convergent syndrome that commonly derives from Alzheimer's disease
      (AD), microvascular brain injury (mVBI), and Lewy body disease (LBD), and that
      these diseases have prevalent subclinical forms that also are commonly co-morbid.
      The existence of subclinical diseases highlights potential opportunities to
      intervene before the development of clinically apparent impairments. Our
      observations suggest that some such interventions already may exist to suppress
      processes of AD (statin therapy) or mVBI (treatment of hypertension). Reduced
      burden of LBD is associated with cigarette smoking; although smoking is not
      recommended as an intervention, these exposure data may provide clues to
      alternative neuroprotective mechanisms. Self reported anti-oxidant
      supplementation was without apparent effect in this cohort on indices of AD,
      mVBI, or LBD. Continued observational studies of brain aging will provide further
      insight into the convergent complexity of the dementia syndrome and its
      subclinical forms as well as highlight potential interventions that will require
      validation in clinical trials.

PMID- 22471860
TI  - Overview and findings from the religious orders study.
AB  - The Religious Orders Study is a longitudinal clinical-pathologic cohort study of
      aging and Alzheimer's disease (AD). In this manuscript, we summarize the study
      methods including the study design and describe the clinical evaluation,
      assessment of risk factors, collection of ante-mortem biological specimens, brain
      autopsy and collection of selected postmortem data. THE RESULTS: (1) review the
      relation of neuropathologic indices to clinical diagnoses and cognition proximate
      to death; (2) examine the relation of risk factors to clinical outcomes; (3)
      examine the relation of risk factors to measures of neuropathology; and (4)
      summarize additional study findings. We then discuss and contextualize the study
      findings.

PMID- 22471863
TI  - A population-based clinicopathological study in the oldest-old: the 90+ study.
AB  - Population-based longitudinal clinicopathological studies provide an ideal
      opportunity to study a variety of risk and protective factors in relation to
      pathology associated with dementia in individuals who are representative of the
      general population. The 90+ Study is a population-based study designed
      specifically to study aging and dementia as well as its neuropathological
      correlates in participants 90 years of age and older. We present demographic and
      pathological data on the first 104 participants to come to autopsy from the brain
      donation component of the study, The 90+ Autopsy Study. Cognitive diagnosis was
      assigned according to diagnostic and statistical manual 4th edition criteria for
      dementia and neuropathological diagnoses were made according to the Consortium to
      Establish a Registry for Alzheimer's Disease protocol. Dementia was present in
      61% of autopsied participants, the majority of whom were diagnosed with
      Alzheimer's disease (85%). Many different types of pathology typically associated
      with dementia were common in the oldest-old, and included neurofibrillary
      tangles, neuritic plaques, diffuse plaques, Lewy bodies, hippocampal sclerosis,
      and cerebral infarctions. Most types of pathology were more frequently found in
      participants suffering from dementia but there was extensive overlap in pathology
      among those with and without dementia. In addition, 22% of demented participants
      did not have sufficient pathology to account for their cognitive loss. Our
      results highlight the poor associations between these common pathological lesions
      and dementia in the oldest-old and the importance of considering many different
      types of pathology, possibly including some yet to be identified, in order to
      account for all dementias in the oldest-old.

PMID- 22471862
TI  - University of Kentucky Sanders-Brown healthy brain aging volunteers: donor
      characteristics, procedures and neuropathology.
AB  - Cognitively intact elderly research volunteers at the University of Kentucky have
      been recruited, followed longitudinally, and autopsied with extensive
      neuropathological evaluations since 1989. To date, the cohort has recruited 1,030
      individuals with 552 participants being actively followed, 363 deceased, and 273
      autopsied. An extensive database has been constructed with continuous updates
      that include textured clinical, neuropsychological, neuroimaging, and
      pathological information. The history, demographics, clinical observations, and
      pathological features of this research cohort are described. We also explain some
      of the evolving methodologies and the academic contributions that have been made
      due to this motivated group of older Kentuckians.

PMID- 22471864
TI  - Neuropathological correlates of falling in the CC75C population-based sample of
      the older old.
AB  - BACKGROUND: Previous imaging studies have suggested links between brain
      pathologies and factors that are associated with falls such as gait, balance and
      daily function. Possible neuropathological correlates of older people's falls
      have been suggested based on brain imaging studies, but to date none have been
      examined in brain tissue. METHODS: Falls data collected from repeated surveys of
      a population-based cohort of individuals aged at least 75 years old at baseline
      were related to neuropathological data collected from post-mortem examination of
      the study's associated brain donor collection (n=212). RESULTS: Amongst people
      without dementia, most cerebrovascular neuropathological features examined,
      particularly white matter pallor, microinfarcts and microscopic atherosclerosis,
      were increasingly common across the subgroups categorised by no reports of
      falling, only one or at least two reports of falling. The overall burden of
      pathology was greater in those with dementia, but only microinfarcts showed a
      similar increase with respect to reported falling status. CONCLUSIONS:
      Subclinical pathologies sharing a common vascular origin are associated with
      increased falling amongst people with no dementia, as are microinfarcts in those
      with dementia. Although further research is needed to address the mechanisms of
      falls and their neuropathological correlates, the findings from the current study
      would suggest that if cerebrovascular disease prevention reduces vascular
      neuropathology changes this may have direct benefits in reducing falls amongst
      older people with or without dementia.

PMID- 22471865
TI  - The Framingham Brain Donation Program: neuropathology along the cognitive
      continuum.
AB  - The Framingham Heart Study has enrolled 3 generations of participants, the
      original cohort (gen 1) enrolled in 1948, the offspring cohort (gen 2) enrolled
      in 1971 and the third generation enrolled in 2002. Participants have been
      undergoing prospective surveillance for incident stroke and dementia and embedded
      within this cohort is the voluntary Framingham Brain Donation Program that was
      begun in 1997. Participants who register to become brain donors have had one or
      more brain MR and cognitive test batteries administered. In addition, they
      undergo neurological evaluation as indicated, record review and post-mortem next
      of-kin interview to determine the presence, type and extent of antemortem,
      clinical neurological diagnoses and to assign a retrospective clinical dementia
      rating (CDR) Scale score. Between 1997 and 2009 there were 1806 deaths, 186 of
      which were among registered brain donors and of these 139 brains could be
      examined. 58% were deemed cognitively normal at death. We present results for 3
      projects; the first was to examine the sensitivity and specificity of our
      clinical diagnosis against the gold standard of pathological AD in 59 persons who
      underwent detailed cognitive assessment in the two years prior to death; we
      observed a 77.3% sensitivity (2 persons with AD were diagnosed clinically as Lewy
      body dementia) and a 91.9% specificity. The second examined the correlation of
      regional Alzheimer-type pathology to cognitive status at death among 34 persons
      who were over the age of 75 and without any significant vascular or alternative
      neurodegenerative pathology and found that neurofibrillary tangle counts
      distinguished between persons who were controls, had mild cognitive impairment,
      mild or moderate dementia; tangles in dorsolateral frontal cortex best
      distinguished MCI and controls. The third project examined the extent and
      severity of vascular pathology, again in a larger sample of varying cognitive
      abilities and in a subsample of persons with either amnestic or nonamnestic MCI.
      We observed that an aggregate ischemic injury score was significantly higher in
      persons with a CDR score of 0.5 than in normal controls.

PMID- 22471866
TI  - The Honolulu-Asia Aging Study: epidemiologic and neuropathologic research on
      cognitive impairment.
AB  - The Honolulu-Asia Aging Study (HAAS) is a longitudinal epidemiologic
      investigation of rates, risk factors, and neuropathologic abnormalities
      associated with cognitive decline and dementia in aged Japanese-American men. The
      project was established in 1991 and will be brought to closure in 2012. Age
      specific rates of total dementia and the major specific types of dementia in HAAS
      participants are generally similar to those reported from other geographic,
      cultural, and ethnic populations. Risk factors for dementia in the HAAS include
      midlife hypertension and other factors previously shown to influence
      cardiovascular disease. The autopsy component of the project has yielded novel
      findings, the most illuminating of which is the demonstration of 5 important
      lesion types linked independently to cognitive impairment. While one of these-
      generalized atrophy--is strongly associated with both Alzheimer lesions and
      microinfarcts, it also occurs in the absence of these lesions and is
      independently correlated with dementia. Each lesion type is viewed as
      representing a distinct underlying pathogenic process. Their summed influences is
      an especially robust correlate of dementia in the months and years prior to
      death.

PMID- 22471868
TI  - The Minority Aging Research Study: ongoing efforts to obtain brain donation in
      African Americans without dementia.
AB  - The Minority Aging Research Study (MARS) is a longitudinal, epidemiologic cohort
      study of decline in cognitive function and risk of Alzheimer's disease (AD) in
      older African Americans, with brain donation after death added as an optional
      component for those willing to consider organ donation. In this manuscript, we
      first summarize the study design and methods of MARS. We then provide details of
      ongoing efforts to achieve neuropathologic data on over 100 African Americans
      participating in MARS and in three other clinical-pathologic cohort studies at
      Rush University Medical Center. The results examine strategies for recruiting and
      consenting African Americans without dementia; (2) efforts to maintain high rates
      of follow-up participation; (3) strategies for achieving high rates of agreement
      to brain donation; and (4) the methodology of obtaining rapid brain autopsy at
      death. The implications of these efforts are discussed.

PMID- 22471869
TI  - The Nun Study: risk factors for pathology and clinical-pathologic correlations.
AB  - The Nun Study was the first cohort study to enroll and follow a large, well
      defined population that included demented and non-demented participants, all of
      whom agreed to donate their brains for research. The inclusion of systematic
      neuropathologic analysis in this study has resulted in a greater understanding of
      the role of Alzheimer and vascular pathology in the expression of memory deficits
      and dementia and has provided data showing that biomarkers for the pathology may
      be evident many decades earlier in adult life. Findings related to neuropathology
      in this study have included the following: (1) Although clinical outcomes were
      strongly correlated with Alzheimer neuropathology, about one-third of the
      participants fulfilling criteria for neuropathologic Alzheimer's disease (AD)
      were not demented at the time of death. (2) Brain infarcts by themselves had
      little effect on cognitive status, but played an important role in increasing the
      risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was
      strongly correlated with Braak neurofibrillary stage even in participants with
      normal cognitive function. (4) A linguistic characteristic of essays written in
      early adult life, idea density, had a strong association with not only clinical
      outcomes in late life, but the severity of Alzheimer neuropathology as well. (5)
      The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but
      not vascular pathology.

PMID- 22471870
TI  - The neuropathology of vascular disease in the Medical Research Council Cognitive
      Function and Ageing Study (MRC CFAS).
AB  - BACKGROUND: Vascular disease is associated with increased risk of dementia.
      Vascular health worsens with age. We investigated the relationship between self
      reported vascular disease and brain pathology. METHODS: Brain donations to the
      population-based MRC Cognitive Function and Ageing Study (n=456, age range 66-103
      years) were assessed using a standard protocol for Alzheimer's disease (AD) and
      cerebrovascular pathology. History of stroke, angina, diabetes, medicated
      hypertension and heart attack were identified from self- and proxy-report
      interviews, retrospective informant interviews and death certificates. Logistic
      regression was used to estimate associations between each health condition and
      dichotomised neuropathological variables adjusted for age and sex. RESULTS:
      Stroke (36%), angina (23%), diabetes (12%), medicated hypertension (35%) and
      heart attack (22%) were frequently reported. Self-reported stroke was strongly
      associated with vascular, but not AD pathology. Medicated hypertension was
      associated with increased microinfarcts (OR=2.1, 95% CI=1.3-3.7) and less severe
      neocortical tangles (OR=0.5, 95% CI=0.3-0.8) and cerebral amyloid angiopathy
      (OR=0.5, 95% CI=0.3-0.8). Heart attack was associated with increased
      microinfarcts (OR=2.1, 95% CI=1.2-3.9). CONCLUSIONS: Vascular risk factors were
      not associated with an increased burden of AD pathology at death in old age. A
      positive association between indices of systemic cardiovascular health (treated
      hypertension and ischaemic heart disease) and cerebral microinfarcts emerged. The
      findings support the view that cerebral small vessel disease and cardiovascular
      disease are interrelated. Microinfarcts are emerging as an important correlate of
      age-related vascular cognitive impairment and the findings add weight to the
      argument for strategies to improve general cardiovascular health as a potential
      preventative strategy against cognitive decline in later life.

PMID- 22471867
TI  - Overview and findings from the rush Memory and Aging Project.
AB  - The Memory and Aging Project is a longitudinal, epidemiologic clinical-pathologic
      cohort study of common chronic conditions of aging with an emphasis on decline in
      cognitive and motor function and risk of Alzheimer's disease (AD). In this
      manuscript, we first summarize the study design and methods. Then, we present
      data on: (1) the relation of motor function to cognition, disability, and death;
      (2) the relation of risk factors to cognitive and motor outcomes, disability and
      death; (3) the relation of neuropathologic indices to cognitive outcomes; (4) the
      relation of risk factors to neuropathologic indices; and (5) additional study
      findings. The findings are discussed and contextualized.

PMID- 22471871
TI  - Preparation and characterization of amphiphilic triblock terpolymer-based
      nanofibers as antifouling biomaterials.
AB  - Antifouling surfaces are critical for the good performance of functional
      materials in various applications including water filtration, medical implants,
      and biosensors. In this study, we synthesized amphiphilic triblock terpolymers
      (tri-BCPs, coded as KB) and fabricated amphiphilic nanofibers by electrospinning
      of solutions prepared by mixing the KB with poly(lactic acid) (PLA) polymer. The
      resulting fibers with amphiphilic polymer groups exhibited superior antifouling
      performance to the fibers without such groups. The adsorption of bovine serum
      albumin (BSA) on the amphiphilic fibers was about 10-fold less than that on the
      control surfaces from PLA and PET fibers. With the increase of the KB content in
      the amphiphilic fibers, the resistance to adsorption of BSA was increased. BSA
      was released more easily from the surface of the amphiphilic fibers than from the
      surface of hydrophobic PLA or PET fibers. We have also investigated the
      structural conformation of KB in fibers before and after annealing by contact
      angle measurements, transmission electron microscopy (TEM), energy-dispersive X
      ray spectroscopy (EDX), and coarse-grained molecular dynamics (CGMD) simulation
      to probe the effect of amphiphilic chain conformation on antifouling. The results
      reveal that the amphiphilic KB was evenly distributed within as-spun hybrid
      fibers, while migrated toward the core from the fiber surface during thermal
      treatment, leading to the reduction in antifouling. This suggests that the
      antifouling effect of the amphiphilic fibers is greatly influenced by the
      arrangement of amphiphilic groups in the fibers.

PMID- 22471872
TI  - Erbium: yttrium-aluminium-garnet (Er:YAG) laser treatment of penile pearly
      papules.
AB  - BACKGROUND: Penile pearly papules (PPP) are benign angiofibromas of the penis,
      frequently misdiagnosed as genital warts (condylomata acuminata). The lesions are
      often the reason for significant distress of the patient and his sexual partner,
      thus requiring occasional treatment, removing the lesions in a non-aggressive
      manner. METHODS: Forty-five patients with PPP were treated with 2940 nm Er:YAG
      laser (Skinlight, FOTONA, Slovenia) in ablation mode. The treatment parameters
      were: energy 400-500 mJ, spot diameter 1.5-3 mm, repetition rate 8-10 Hz and
      energy density 5.8-28.9 J/cm(2). RESULTS: PPP were successfully removed in all 45
      patients in 1-6 (mean +/- SD = 2.0 +/- 1.3) sessions without complications.
      CONCLUSION: Er:YAG laser ablation represents an efficient method of removal of
      PPP. The procedure can be performed in outpatient clinics.

PMID- 22471873
TI  - Paediatrics and the doctor-soldier.
AB  - Sick and injured children, like combatants wounded by shot and shell in war, are
      disproportionately represented in the tallies of both man-made and national
      disasters. Paediatricians have a particularly proud heritage of military service,
      a nexus dating in Australia from the early 19th century. This paper traces this
      link between service to children in peacetime and the care of servicemen, women
      and children in times of war and disaster. The extraordinary record of Australian
      'paediatric' doctors who also served in the Gallipoli Campaign (1915) is
      documented as an illustration of this duality. Paediatricians who serve in the
      Defence Reserves and in civilian non-government organisations which respond to
      disasters and civil wars have special credentials in their advocacy for the
      protection of children enmeshed in conflict or disaster. Such applies
      particularly to the banning of the recruitment and use of child soldiers; support
      for children caught up in refugee and illegal immigrant confrontations; and
      continued advocacy for greater international compliance with the Ottawa
      Convention to ban the use of anti-personnel landmines. Volunteering for such
      service must occur in cold 'down time', ensuring that paediatricians are trained
      in disaster and conflict response, when such challenges inevitably confront the
      paediatricians of the future.

PMID- 22471874
TI  - Long-term antihypertensive efficacy of losartan/hydrochlorothiazide combination
      therapy on home blood pressure control.
AB  - Angiotensin receptor blocker (ARB)/hydrochlorothiazide (HCTZ) combination therapy
      has been shown to produce a prompt reduction in clinic blood pressure (BP)
      without serious adverse effects; however, long-term antihypertensive efficacy on
      home BP has not been fully investigated. In this open-label multicenter
      observational study, a total of 151 hypertensive patients uncontrolled with
      antihypertensive regimens including standard dose of ARBs were switched to the
      fixed-dose combination of losartan (50 mg)/HCTZ (12.5 mg) (mean age 66.9 +/- 9.5
      years, 51% male, 19% with diabetes mellitus, and 57% with dyslipidemia). After 3
      months, losartan/HCTZ treatment significantly reduced mean home systolic
      BP/diastolic BP from a baseline level of 153 +/- 11/85 +/- 9 mm Hg to 136 +/-
      12/77 +/- 10 mm Hg (P < .001) and mean clinic BP from 158 +/- 9/87 +/- 9 to 136
      +/- 12/77 +/- 10 (P < .001), which were maintained through the study period of 12
      months (132 +/- 11/75 +/- 9 and 136 +/- 12/77 +/- 10; home and clinic BP at 12
      months, respectively, P < .001). Furthermore, younger patients (< 65 years)
      receiving ARB monotherapy at the start of the study showed a significantly
      greater reduction in home BP, but not in clinic BP, compared with elderly
      patients (>= 65 years). In conclusion, losartan/HCTZ combination therapy exerted
      a 1-year long-term efficacy on home BP as well as clinic BP. In patients
      uncontrolled with ARB monotherapy, the antihypertensive efficacy on home BP is
      more pronounced in younger patients compared with that in elderly patients.

PMID- 22471875
TI  - Do you think it's a disease? a survey of medical students.
AB  - BACKGROUND: The management of medical conditions is influenced by whether
      clinicians regard them as "disease" or "not a disease". The aim of the survey was
      to determine how medical students classify a range of conditions they might
      encounter in their professional lives and whether a different name for a
      condition would influence their decision in the categorisation of the condition
      as a 'disease' or 'not a disease'. METHODS: We surveyed 3 concurrent years of
      medical students to classify 36 candidate conditions into "disease" and "non
      disease". The conditions were given a 'medical' label and a (lay) label and
      positioned where possible in alternate columns of the survey. RESULTS: The
      response rate was 96% (183 of 190 students attending a lecture): 80% of students
      concurred on 16 conditions as "disease" (eg diabetes, tuberculosis), and 4 as
      "non-disease" (eg baldness, menopause, fractured skull and heat stroke). The
      remaining 16 conditions (with 21-79% agreement) were more contentious (especially
      obesity, infertility, hay fever, alcoholism, and restless leg syndrome). Three
      pairs of conditions had both a more, and a less, medical label: the more medical
      labels (myalgic encephalomyelitis, hypertension, and erectile dysfunction) were
      more frequently classified as 'disease' than the less medical (chronic fatigue
      syndrome, high blood pressure, and impotence), respectively, significantly
      different for the first two pairs. CONCLUSIONS: Some conditions excluded from the
      classification of "disease" were unexpected (eg fractured skull and heat stroke).
      Students were mostly concordant on what conditions should be classified as
      "disease". They were more likely to classify synonyms as 'disease' if the label
      was medical. The findings indicate there is still a problem 30 years on in the
      concept of 'what is a disease'. Our findings suggest that we should be addressing
      such concepts to medical students.

PMID- 22471876
TI  - Double-robust semiparametric estimator for differences in restricted mean
      lifetimes in observational studies.
AB  - Restricted mean lifetime is often of direct interest in epidemiologic studies
      involving censored survival times. Differences in this quantity can be used as a
      basis for comparing several groups. For example, transplant surgeons,
      nephrologists, and of course patients are interested in comparing posttransplant
      lifetimes among various types of kidney transplants to assist in clinical
      decision making. As the factor of interest is not randomized, covariate
      adjustment is needed to account for imbalances in confounding factors. In this
      report, we use semiparametric theory to develop an estimator for differences in
      restricted mean lifetimes although accounting for confounding factors. The
      proposed method involves building working models for the time-to-event and
      coarsening mechanism (i.e., group assignment and censoring). We show that the
      proposed estimator possesses the double robust property; i.e., when either the
      time-to-event or coarsening process is modeled correctly, the estimator is
      consistent and asymptotically normal. Simulation studies are conducted to assess
      its finite-sample performance and the method is applied to national kidney
      transplant data.

PMID- 22471878
TI  - High-performance sodium-ion pseudocapacitors based on hierarchically porous
      nanowire composites.
AB  - Electrical energy storage plays an increasingly important role in modern society.
      Current energy storage methods are highly dependent on lithium-ion energy storage
      devices, and the expanded use of these technologies is likely to affect existing
      lithium reserves. The abundance of sodium makes Na-ion-based devices very
      attractive as an alternative, sustainable energy storage system. However,
      electrodes based on transition-metal oxides often show slow kinetics and poor
      cycling stability, limiting their use as Na-ion-based energy storage devices. The
      present paper details a new direction for electrode architectures for Na-ion
      storage. Using a simple hydrothermal process, we synthesized interpenetrating
      porous networks consisting of layer-structured V(2)O(5) nanowires and carbon
      nanotubes (CNTs). This type of architecture provides facile sodium
      insertion/extraction and fast electron transfer, enabling the fabrication of high
      performance Na-ion pseudocapacitors with an organic electrolyte. Hybrid
      asymmetric capacitors incorporating the V(2)O(5)/CNT nanowire composites as the
      anode operated at a maximum voltage of 2.8 V and delivered a maximum energy of
      ~40 Wh kg(-1), which is comparable to Li-ion-based asymmetric capacitors. The
      availability of capacitive storage based on Na-ion systems is an attractive, cost
      effective alternative to Li-ion systems.

PMID- 22471877
TI  - Fracture risk by HIV infection status in perinatally HIV-exposed children.
AB  - The objective of this study was to examine the incidence of fractures in HIV
      infected children and comparable HIV-exposed, uninfected (HEU) children in a
      multicenter, prospective cohort study (PACTG 219/219C) in the United States. The
      main outcome was first fracture during the risk period. Nine fractures occurred
      in 7 of 1326 HIV-infected and 2 of 649 HEU children, corresponding to incidence
      rates of 1.2 per 1000 person-years and 1.1 per 1000 person-years, respectively.
      The incidence rate ratio was 1.1 (95% CI 0.2, 5.5). There was no evidence of a
      substantially increased risk of fracture in HIV-infected compared to HEU
      children.

PMID- 22471879
TI  - Purification and characterization of polyphenol oxidase from cauliflower
      (Brassica oleracea L.).
AB  - Polyphenol oxidase (PPO) of cauliflower was purified to 282-fold with a recovery
      rate of 8.1%, using phloroglucinol as a substrate. The enzyme appeared as a
      single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). The estimated molecular weight of the enzyme was 60 and 54 kDa by SDS-PAGE
      and gel filtration, respectively. The purified enzyme, called phloroglucinol
      oxidase (PhO), oxidized phloroglucinol (K(m) = 3.3 mM) and
      phloroglucinolcarboxylic acid. The enzyme also had peroxidase (POD) activity. At
      the final step, the activity of purified cauliflower POD was 110-fold with a
      recovery rate of 3.2%. The PhO and POD showed the highest activity at pH 8.0 and
      4.0 and were stable in the pH range of 3.0-11.0 and 5.0-8.0 at 5  degrees C for
      20 h, respectively. The optimum temperature was 55  degrees C for PhO and 20 
      degrees C for POD. The most effective inhibitor for PhO was sodium
      diethyldithiocarbamate at 10 mM (IC(50) = 0.64 and K(i) = 0.15 mM), and the most
      effective inhibitor for POD was potassium cyanide at 1.0 mM (IC(50) = 0.03 and
      K(i) = 29 MUM).

PMID- 22471880
TI  - Nanoparticle assemblies in thin films of supramolecular nanocomposites.
AB  - We demonstrated a versatile approach to obtain layered nanoparticle sheets with
      in-plane hexagonal order and 3-D ordered arrays of single nanoparticle chains in
      thin films upon blending nanoparticles with block copolymer (BCP)-based
      supramolecules. Basic understanding on the thermodynamic and kinetic aspects of
      the assembly process paved a path to manipulate these assemblies to meet demands
      in nanoparticle-based device fabrication and understand structure-property
      correlations.

PMID- 22471881
TI  - Guanine bases in DNA G-quadruplex adopt nonplanar geometries owing to solvation
      and base pairing.
AB  - The effect of base pairing and solvation on pyramidalization of the glycosidic
      nitrogen found in the residues of parallel G-quadruplex with NDB ID UDF062 is
      analyzed and explained with theoretical calculations. The extent of the
      pyramidalization depends on the local geometry of the 2'-deoxyguanosine residues,
      namely on their glycosidic torsion and sugar pucker, which are predetermined by
      the 3D-architecture of G-quadruplex. Pyramidal inversion of the glycosidic
      nitrogen found in 2'-deoxyguanosines of G-quadruplex is induced owing to site
      specifically coordinated solvent. Different adiabatic structural constraints used
      for fixing the base-to-sugar orientation of 2'-deoxyguanosine in geometry
      optimizations result in different extents of pyramidalization and induce
      pyramidal inversion of the glycosidic nitrogen. These model geometry constraints
      helped us analyze the effect of real constraints represented by explicit
      molecular environment of selected residues of the G-quadruplex. The maximal
      extent of the glycosidic nitrogen pyramidalization found in the high-resolution
      crystal structure corresponds to the calculation to deformation energy of only 1
      kcal mol(-1). The out-of-plane deformations of nucleobases thus provide a way for
      compensating the site-specific external environmental stress on the G-quadruplex.

PMID- 22471882
TI  - Biologics in oral medicine: ulcerative disorders.
AB  - Inflammatory ulcerative diseases of the oral mucosa are wide ranging but include
      especially aphthous and aphthous-like ulceration, vesiculobullous disorders and
      erosive lichen planus (LP). While most patients with these conditions respond to
      conventional topical and/or systemic immunosuppressive agents, treatment
      resistant cases remain challenging. In these, the use of biologics such as tumour
      necrosis factor alpha (TNF-alpha) inhibitors or rituximab may be of benefit. This
      article reviews the use of biologics in ulcerative oral conditions, highlighting
      potential benefits, adverse effects and principles of use and future
      developments. TNF-alpha inhibitors such as infliximab can be effective in
      inducing resolution in oral aphthous and aphthous-like ulcers and may be an
      appropriate therapy in those patients in which disease is severe and refractory
      to, or patients are intolerant of, traditional immunomodulatory regimens. There
      would also seem support and rationale for use of biologics (mainly rituximab) in
      pemphigus but not in oral LP or other oral ulcerative conditions.

PMID- 22471883
TI  - Neuropathology of the hippocampus in FTLD-Tau with Pick bodies: a study of the
      BrainNet Europe Consortium.
AB  - AIMS: Frontotemporal lobar degeneration with Pick bodies (Pick's disease) is
      characterized by the presence of tau immunoreactive spherical structures in the
      cytoplasm of neurones. In view of confusion about the molecular pathology of
      Pick's disease, we aimed to evaluate the spectrum of tau pathology and
      concomitant neurodegeneration-associated protein depositions in the
      characteristically affected hippocampus. METHODS: We evaluated immunoreactivity
      (IR) for tau (AT8, 3R, 4R), alpha-synuclein, TDP43, p62, and ubiquitin in the
      hippocampus, entorhinal and temporal cortex in 66 archival cases diagnosed
      neuropathologically as Pick's disease. RESULTS: Mean age at death was 68.2 years
      (range 49-96). Fifty-two (79%) brains showed 3R immunoreactive spherical
      inclusions in the granule cells of the dentate gyrus. These typical cases
      presented mainly with the behavioural variant of frontotemporal dementia,
      followed by progressive aphasia, mixed syndromes or early memory disturbance.
      alpha-Synuclein IR was seen only in occasional spherical tau-positive inclusions,
      TDP-43 IR was absent, and 4R IR was present only as neurofibrillary tangles in
      pyramidal neurones. Abeta IR was observed in 16 cases; however, the overall level
      of Alzheimer's disease-related alterations was mainly low or intermediate (n =
      3). Furthermore, we identified six cases with unclassifiable tauopathy.
      CONCLUSIONS: (i) Pick's disease may occur also in elderly patients and is
      characterized by a relatively uniform pathology with 3R tau inclusions
      particularly in the granule cells of dentate gyrus; (ii) even minor deviation
      from these morphological criteria suggests a different disorder; and (iii)
      immunohistological revision of archival cases expands the spectrum of tauopathies
      that require further classification.

PMID- 22471885
TI  - Psoriasis prevalence among the 2009 AAD National Melanoma/Skin Cancer Screening
      Program participants.
AB  - BACKGROUND: Validated epidemiological estimates of the prevalence of skin
      diseases remain an unmet challenge. Most patients in many health care systems do
      not see dermatologists for skin problems. Assessments based on claims data or
      self-report are likely to contain substantial misclassification. Population-based
      in-person dermatological exams have proven impractical because of the number of
      patients required. However, in the US, there is a large skin cancer screening
      program where volunteer dermatologists assess almost 100,000 people annually.
      OBJECTIVE: To evaluate the utility of this program for the assessment of other
      diseases. METHODS: Information concerning prior diagnosis of psoriasis, type of
      insurance and physician's current assessment of psoriasis was captured as part of
      the American Academy of Dermatology National Melanoma/Skin Cancer Screening
      Program. A modified form was provided to a subset of participant sites. Overall
      and subgroup prevalence of psoriasis was analysed. Crude and adjusted results are
      presented for comparison to the US population. RESULTS: Among the 2991
      participants, 86% answered the self-report psoriasis question. A previous
      diagnosis of psoriasis was reported by 5.1% of them. This proportion was greater
      than the prevalence of physician documented diagnosis of psoriasis (2.8%).
      Analyses with different assumptions to account for missing values and weighting
      based on US population estimates yielded prevalence values ranging from 1.2% to
      3.4%. CONCLUSION: This project, although limited by missing data, is consistent
      with previous findings that psoriasis prevalence is between 2.2% and 4.6% in the
      US. It demonstrates the potential to evaluate prevalence of other skin conditions
      through existing national activities.

PMID- 22471884
TI  - Illness meanings and experiences for pre-ulcer and ulcer conditions of Buruli
      ulcer in the Ga-West and Ga-South Municipalities of Ghana.
AB  - BACKGROUND: Ghana is a Buruli ulcer (BU) endemic country yet there is paucity of
      socio-cultural research on BU. Examining distinctive experiences and meanings for
      pre-ulcers and ulcers of BU may clarify the disease burden, illness experience
      and local perceptions of causes and spread, and environmental features of BU,
      which are useful to guide public health programmes and future research. This
      study aimed to explain local meanings and experiences of BU for persons with pre
      ulcers and ulcers in the Ga-West and Ga-South municipalities in Accra. METHODS:
      Semi-structured interviews based on the Explanatory Model Interview Catalogue
      framework were administered to 181 respondents comprising 15 respondents with pre
      ulcers and 166 respondents with ulcers. The Wilcoxon rank-sum test was used to
      compare categories of illness experiences (PD) and perceived causes (PC) among
      respondents with pre-ulcer and ulcer conditions. The Fisher's exact test was used
      to compare the most troubling PD and the most important PC variables. Qualitative
      phenomenological analysis of respondents' narratives clarified illness
      experiences and meanings with reference to PC and PD variables. RESULTS: Families
      of respondents with pre-ulcers and the respondents themselves were often anxious
      about disease progression, while families of respondents with ulcers, who had to
      give care, worried about income loss and disruption of school attendance.
      Respondents with pre-ulcers frequently reported swimming in ponds and rivers as a
      perceived cause and considered it as the most important PC (53.3%). Respondents
      with ulcers frequently attributed their BU illness to witchcraft (64.5%) and
      respondents who claimed they had no water contact, questioned the credibility of
      health messages CONCLUSIONS: Affected persons with pre-ulcers are likely to delay
      treatment because of social and financial constraints and the absence of pain.
      Scepticism on the role of water in disease contagion and prolonged healing is
      perceived to make ideas of witchcraft as a PC more credible, among respondents
      with ulcers. Health messages should address issues of locally perceived risk and
      vulnerability. Guided by study findings, further research on the role of
      environmental, socio-cultural and genetic factors in BU contagion, is also needed
      to clarify and formulate health messages and strengthen public health
      initiatives.

PMID- 22471886
TI  - In vitro evaluation of Malassezia pachydermatis susceptibility to azole compounds
      using E-test and CLSI microdilution methods.
AB  - Dermatitis caused by Malassezia spp., one of most common skin disease in dogs,
      requires prolonged therapy and/or high doses of antifungal agents. In the present
      study, the antifungal susceptibility of M. pachydermatis to ketoconazole (KTZ),
      fluconazole (FLZ), itraconazole (ITZ), posaconazole (POS) and voriconazole (VOR)
      was evaluated in vitro using both CLSI reference broth microdilution (CLSI BMD)
      and E-test. A total of 62 M. pachydermatis strains from dogs with and without
      skin lesions were tested. M. pachydermatis strains were susceptible to ITZ, KTZ
      and POS using both test methods, with the highest MIC found in tests of FLZ.
      Essential agreement between the two methods ranged from 87.1% (VOR) to 91.9%
      (ITZ), and categorical agreement from 74.2% (FLZ) to 96.8% (ITZ). Minor error
      discrepancies were observed between the two methods, with major discrepancies
      observed for KTZ. A higher MIC(50) value for FLZ was noted with M. pachydermatis
      genotype B. The MICs(50) of M. pachydermatis genotype B for KTZ, VOR and POS were
      higher in isolates from dogs with skin lesions than those in isolates from
      animals without skin lesions. The results suggest a link between genotypes of M.
      pachydermatis and in vitro drug susceptibility. The categorical agreement for
      both E-test and CLSI BMD methods found in this investigation confirms the E-test
      as a reliable diagnostic method for routine use in clinical mycology
      laboratories.

PMID- 22471887
TI  - Good sex/bad sex: the individualised focus of US HIV prevention policy in sub
      Saharan Africa, 1995-2005.
AB  - The expanding reliance on the health sciences to address social problems is well
      documented, as are the effects of the social construction of public (health)
      problems on 'target' populations, intervention design and broader social systems.
      Less attention has been given in the literature to the cultural meanings that
      configure public health efforts themselves. This study demonstrates how the
      cultural understandings of sex and sexuality that inform US human
      immunodeficiency virus (HIV) prevention policy in sub-Saharan Africa shape policy
      recommendations. Based on an analysis of 119 US policy documents, a relatively
      stable and highly gendered narrative of sexual risk was found across the Clinton
      and (G.W.) Bush administrations. This narrative locates HIV risk in (what is
      constructed to be) the inevitable clash between women's sexuality and men's
      sexuality, and delineates HIV risk by the form of relationship in which sex
      occurs. The two narratives diverge at this point, offering different definitions
      of 'bad' sex and 'good' sex. This divergence helps to explain the different
      prevention foci of the administrations - condoms during the Clinton era and
      abstinence-outside-of-marriage during the Bush administration. In both cases, the
      sexual risk narrative points to individual targeted prevention strategies, even
      as the policy identifies structural factors as driving global HIV epidemics.

PMID- 22471888
TI  - Role of saponins for the anticonvulsant effect of adventitious roots of Ficus
      religiosa.
AB  - CONTEXT: The adventitious roots of Ficus religiosa L. (Moraceae) have been
      extensively used in traditional medicine for treatment of several disorders,
      including epilepsy. OBJECTIVE: To investigate the possible anticonvulsant effect
      of the adventitious roots of Ficus religiosa, and to find the biologically active
      fraction, to substantiate its traditional use in epilepsy. METHODS: The
      hydroethanolic extract of adventitious roots (5, 10, and 20 mg/kg; i.p.) of Ficus
      religiosa and its different fractions (hexane, chloroform, ethyl acetate,
      butanol, aqueous, saponins-rich, and saponins-lacking) at a dose equivalent to 20
      mg/kg of the extract were administered 30 min prior to the induction of maximal
      electroshock (MES) and pentylenetetrazol (PTZ) convulsions. Duration of tonic
      hind-limb extension (THLE) and latency to clonic convulsions were noted in MES
      and PTZ tests, respectively. Neurotoxicity was assessed using rotarod test.
      RESULTS: Treatment with the root extract (5, 10, and 20 mg/kg; i.p.), butanolic
      (6 mg/kg; i.p.) and saponins-rich fractions (3.4 mg/kg; i.p.) significantly (p <
      0.05) decreased the duration of THLE in MES test, as compared to control. The
      same treatment also significantly (p < 0.05) increased the latency to PTZ-induced
      clonic convulsions in comparison to control. The other fractions were found to be
      ineffective. The root extract and its active fractions at their effective doses
      showed no neurotoxic effects. CONCLUSION: The present study concluded that the
      hydroethanolic extract of adventitious roots of Ficus religiosa has
      anticonvulsant activity. Retention of anticonvulsant effect in the saponins-rich
      fraction-treated animals indicated the role of saponins for the activity.

PMID- 22471889
TI  - Clinical characteristics of Becker's nevus in children: report of 118 cases from
      Italy.
AB  - We performed a retrospective study covering a 10-year period (January 1997
      January 2007) on children referred to our unit or followed up for Becker's nevus
      (BN). The aim of this study was to better define the characteristics of BN in
      childhood, when this hypermelanosis is more frequent than the limited number of
      studies might suggest. Our data show that BN in children has predilection sites
      similar to those in adults, but hypertrichosis is rarer. Sun exposure does not
      appear to play an etiopathogenetic role. The higher incidence in men reported in
      adult case studies was not found in children. During and after puberty,
      androgenic stimulation is known to play a pathogenetic role in BN, especially in
      men, but our cases were mostly younger than 6 years old.

PMID- 22471890
TI  - Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue
      sarcoma patients.
AB  - BACKGROUND: It is well known that osteopontin (OPN) plays an important role in
      tumor progression and that a high OPN expression level in several tumor entities
      correlates with poor prognosis in cancer patients. However, little is known about
      the prognostic relevance of the OPN mRNA splice variants. METHODS: We analyzed
      the mRNA expression levels of different OPN splice variants in tumor tissue of
      124 soft tissue sarcoma (STS) patients. Quantitative real-time PCR (qRT-PCR) was
      used to analyze the mRNA expression level of three OPN splice variants (OPN-a, -b
      and -c). RESULTS: The multivariate Cox's proportional hazard regression model
      revealed that high mRNA expression levels of OPN splice variants are
      significantly associated with poor prognosis in STS patients (n = 124). Women (n
      = 68) with high mRNA expression levels of OPN-a and OPN-b have an especially
      elevated risk of tumor-related death (OPN-a: RR = 3.0, P = 0.01, CI = 1.3-6.8;
      OPN-b: RR = 3.4, P = 0.01, CI = 1.4-8.2). In particular, we found that high mRNA
      expression levels of OPN-b and OPN-c correlated with a high risk of tumor-related
      death in STS patients that received radiotherapy (n = 52; OPN-b: RR = 10.3, P <
      0.01, CI = 2.0-53.7; OPN-c: RR = 11.4, P < 0.01, CI = 2.2-59.3). CONCLUSION: Our
      study shows that elevated mRNA expression levels of OPN splice variants are
      negative prognostic and predictive markers for STS patients. Further studies are
      needed to clarify the impact of the OPN splice variants on prognosis.

PMID- 22471891
TI  - Effect of betaine supplementation on cycling sprint performance.
AB  - PURPOSE: To examine the effect of betaine supplementation on cycling sprint
      performance. METHODS: Sixteen recreationally active subjects (7 females and 9
      males) completed three sprint tests, each consisting of four 12 sec efforts
      against a resistance equal to 5.5% of body weight; efforts were separated by 2.5
      min of cycling at zero resistance. Test one established baseline; test two and
      three were preceded by seven days of daily consumption of 591 ml of a
      carbohydrate-electrolyte beverage as a placebo or a carbohydrate-electrolyte
      beverage containing 0.42% betaine (approximately 2.5 grams of betaine a day);
      half the beverage was consumed in the morning and the other half in the
      afternoon. We used a double blind random order cross-over design; there was a 3
      wk washout between trials two and three. Average and maximum peak and mean power
      were analyzed with one-way repeated measures ANOVA and, where indicated, a
      Student Newman-Keuls. RESULTS: Compared to baseline, betaine ingestion increased
      average peak power (6.4%; p < 0.001), maximum peak power (5.7%; p < 0.001),
      average mean power (5.4%; p = 0.004), and maximum mean power (4.4%; p = 0.004)
      for all subjects combined. Compared to placebo, betaine ingestion significantly
      increased average peak power (3.4%; p = 0.026), maximum peak power max (3.8%; p =
      0.007), average mean power (3.3%; p = 0.034), and maximum mean power (3.5%; p =
      0.011) for all subjects combined. There were no differences between the placebo
      and baseline trials. CONCLUSIONS: One week of betaine ingestion improved cycling
      sprint power in recreationally active males and females.

PMID- 22471892
TI  - Identifying the last supper: utility of the DNA barcode library for bloodmeal
      identification in ticks.
AB  - Ticks are among the most important vectors of disease in the Northern Hemisphere,
      and a better understanding of their feeding behaviour and life cycle is critical
      to the management and control of tick-borne zoonoses. DNA-based tools for the
      identification of residual bloodmeals in hematophagous arthropods have proven
      useful in the investigation of patterns of host use in nature. Using a blind test
      approach, we challenged the utility of the DNA barcode library for the
      identification of vertebrate bloodmeals in engorged, field-collected Ixodes
      scapularis. Universal vertebrate primers for the COI barcode region successfully
      amplified DNA from the host bloodmeal and only rarely amplified tick DNA. Of the
      61 field-collected ticks, conclusive genus- and species-level identification was
      possible for 72% of the specimens. In all but two cases, barcode-based
      identification of the bloodmeal was consistent with the morphological
      identification of the vertebrate host the ticks were collected from. Possible
      explanations for mismatches or ambiguities are presented. This study validates
      the utility of the DNA barcode library as a valuable and reliable resource for
      the identification of unknown bloodmeals in arthropod vectors of disease. Future
      directions aimed at the refinement of these techniques to gain additional
      information and to improve the amplification success of digested vertebrate DNA
      in tick bloodmeals are discussed.

PMID- 22471893
TI  - Determining optimal neighborhood size for ecological studies using leave-one-out
      cross validation.
AB  - We employed a leave-one-out cross validation to determine optimally sized
      neighborhood. Variations between a single point and the other points within each
      filter size for all the points in the study area were evaluated, and the mean
      squared error (MSE) for each filter was calculated. The filter with the lowest
      MSE was considered as the optimal neighborhood. The method is useful in
      determining the optimal neighborhood for both geographic and population filters.

PMID- 22471895
TI  - Gunshot residues on dry bone after decomposition--a pilot study.
AB  - Very little literature exists concerning radiochemical and microscopic analyses
      of gunshot wounds in decomposed material, and even less concerning skeletonized
      samples; the most advanced technologies may provide useful indications for the
      diagnosis of suspect lesions, especially if gunshot wounds are no longer
      recognizable. However, we know very little of the survival of gunshot residues
      (GSR) in skeletonized samples. This study examined nine gunshot wounds produced
      on pig heads which then underwent skeletonization for 4 years, and four gunshot
      entries on human heads from judicial cases which were then macerated to the bone
      in water; the samples underwent scanning electron microscopy coupled with energy
      dispersive X-ray (SEM-EDX) analysis. Positive results for GSR were observed only
      in four of the nine animal samples and in all four human samples. Among the human
      samples, two lesions showed Pb and Sb, one lesion only Pb, and one Pb, Sb, and
      Ba. This pilot study showed the survival of GSR in skeletal material and
      therefore the crucial importance of SEM-EDX analyses on skeletonized material.
      Further studies are needed in order to ascertain the role of environmental
      modifications of GSR.

PMID- 22471896
TI  - Risk factors for cardiovascular disease are increased in young adults treated
      with stem cell transplantation during childhood.
AB  - We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT
      and in sex and age-matched controls. Three patients (17%), but none of the
      controls, met the criteria for the MetS (p = 0.25). In the patients, we found
      higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol
      (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B
      (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p =
      0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the
      controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was
      significantly correlated inversely with triglycerides (r = -0.64, p = 0.008),
      total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p =
      0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a
      significantly thicker carotid intima layer among the patients than among matched
      controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated
      inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in
      childhood, long-term survivors may be at risk of developing premature CVD.

PMID- 22471897
TI  - Response to Timoney critique of Royal Society of Canada expert panel on oil
      sands.

PMID- 22471898
TI  - The delayed appearance of neurological signs in intrathecal granuloma warrants
      imaging surveillance: a case series and review of the literature.
AB  - Intrathecal pump therapy (ITP) has become a mainstay of treatment for the
      chronic, refractory nonmalignant pain patient. Increasingly, ITP therapy is being
      instituted for the failed back pain population. Inflammatory mass or granuloma is
      a complication that is considered "rare" or "uncommon." In this patient
      population, the symptoms of granuloma can often mimic the symptoms for which the
      patient is being treated. The case series reported here illustrates 4 cases of
      inflammatory mass. One patient presented with paralysis before she was diagnosed,
      and the remainder of the patients were asymptomatic at the time of diagnosis. The
      cases presented illustrate the need for broader education of inflammatory mass
      among nonpain specialists. Etiology, diagnosis and treatment guidelines of
      inflammatory mass are reviewed. The literature reviewed highlights the number of
      patients who present with paralysis as well as the need for regular screening of
      ITP patients.

PMID- 22471899
TI  - A randomized control study of the prevention of hyperpigmentation post Q-switched
      Nd:YAG laser treatment of Hori nevus using topical fucidic acid plus
      betamethasone valerate cream versus fucidic acid cream.
AB  - BACKGROUND: Post-inflammatory hyperpigmentation (PIH) after laser treatment of
      Hori nevus remains problematic. Prevention and treatment of PIH have limited
      success. OBJECTIVE: To study the effects on hyperpigmentation using topical
      antibiotic alone versus combined antibiotic and betamethasone/valerate after 1064
      nm Q-switched Nd:YAG laser treatment of Hori nevus. METHOD: Twenty-five cases of
      Hori nevus treated with Q-switched Nd:YAG laser randomly applied topical fucidic
      acid (control group) or fucidic acid plus betamethasone/valerate (study group) on
      assigned cheek immediately post laser for 2 weeks. Pigmentation was measured
      using the mexameter as melanin index (MI) and erythema index (EI), at baseline,
      2nd and 4th weeks. Photographic evaluation and patient global assessment were
      done at the 4th week. RESULTS: Twenty-three cases completed the study. No patient
      developed side effect from either creams. The comparison of M and E-indexes of
      the control versus the study group revealed no significant difference. However,
      there was a uniform increase of M index of the control group compared to the
      study group. CONCLUSION: Applying topical corticosteroid immediately after laser
      treatment decreased pigmentation. Although not statistically significant, there
      was a tendency for lightening. Future studies are needed with more patients,
      duration of follow-ups and histological studies to assess pigmentary changes.

PMID- 22471900
TI  - Frequent additional tachyarrhythmias in patients with inappropriate sinus
      tachycardia undergoing sinus node modification: an important cause of symptom
      recurrence.
AB  - BACKGROUND: Symptom recurrence following sinus node modification (SNM) for
      inappropriate sinus tachycardia (IST) remains significant despite achieving acute
      procedural success. The impact of non-IST tachyarrhythmias on symptom recurrence
      remains poorly characterized. OBJECTIVES: The objective was to determine the
      prevalence and nature of additional tachyarrhythmias preceding and following SNM
      for IST. METHODS: Consecutive patients with IST undergoing SNM at the University
      of Pennsylvania were studied. SNM was initially performed using an anatomic
      approach targeting the superolateral crista terminalis under intracardiac
      echocardiographic guidance and later using an electrophysiologic approach,
      targeting the site of the earliest right atrial activation during maximum heart
      rate (HR) with isoproterenol infusion. An effort was made to shift the site more
      caudally until a decrease of >25% in resting HR was achieved, with a blunted
      response to isoproterenol and flattening of the P-wave axis in leads III and aVF.
      Patients were followed for arrhythmia recurrence. Tachyarrhythmias were
      documented with electrocardiographic monitoring and then characterized during EP
      study. RESULTS: Thirty-three patients underwent SNM and were followed for a mean
      of 2.0 +/- 1.5 years. During follow-up, 27% developed a non-IST tachyarrhythmia
      and 18% developed recurrent IST. Additionally, 42% of patients had a non-IST
      tachyarrhythmia prior to SNM. CONCLUSIONS: Non-IST tachyarrhythmias are common in
      patients with IST before and after SNM. A major reason for symptom recurrence
      following SNM is development of a non-IST tachyarrhythmia. These tachyarrhythmias
      should be detected and treated to optimize patient outcomes.

PMID- 22471901
TI  - Combination therapy of olmesartan and azelnidipine inhibits sympathetic activity
      associated with reducing oxidative stress in the brain of hypertensive rats.
AB  - It has been demonstrated that the antihypertensive drugs with the antioxidant
      action on the brainstem inhibit the sympathetic activity and consequently
      decrease blood pressure and heart rate (HR) in hypertensive rats. Combination
      drugs of the angiotensin receptor blocker and calcium channel blocker, such as
      olmesartan (OLM)/azelnidipine (AZ) and candesartan (CAN)/amlodipine (AM), are
      widely used for treating hypertension in Japan. In this study, it was
      investigated whether there are differences in the antioxidant effect in the brain
      and the sympathoinhibitory effect between OLM/AZ and CAN/AM combination therapies
      in stroke-prone spontaneously hypertensive rats (SHRSP). OLM/AZ (10/8 mg kg(-1)
      day(-1)), CAN/AM (4/2.5 mg kg(-1) day(-1)), or vehicle was orally administered
      for 30 days to SHRSP. OLM/AZ and CAN/AM markedly decreased systolic blood
      pressure to the same extent. OLM/AZ decreased HR to a greater extent than CAN/AM.
      Urinary norepinephrine excretion as a marker of sympathetic activity was
      unchanged in the CAN/AM group, but reduced in the OLM/AZ group. Oxidative stress
      in the whole brain assessed using the in vivo electron spin resonance method was
      similarly decreased in both OLM/AZ and CAN/AM groups. Importantly, thiobarbituric
      acid reactive substance levels in the brainstem were significantly lower in the
      OLM/AZ group, but not in the CAN/AM group, than in the vehicle group. These
      results suggest that combination therapy of either OLM/AZ or CAN/AM does not
      induce reflex-mediated sympathetic activation despite the marked blood pressure
      reduction, which is associated with an antioxidant effect in the brain regions
      affecting the sympathetic activity. Furthermore, the antioxidant effect in the
      brainstem and the sympathoinhibitory effect of OLM/AZ combination may be greater
      than those of CAN/AM combination treatment.

PMID- 22471902
TI  - The use of regional platforms for managing electronic health records for the
      production of regional public health indicators in France.
AB  - BACKGROUND: In France, recent developments in healthcare system organization have
      aimed at strengthening decision-making and action in public health at the
      regional level. Firstly, the 2004 Public Health Act, by setting 100 national and
      regional public health targets, introduced an evaluative approach to public
      health programs at the national and regional levels. Meanwhile, the
      implementation of regional platforms for managing electronic health records
      (EHRs) has also been under assessment to coordinate the deployment of this
      important instrument of care within each geographic area. In this context, the
      development and implementation of a regional approach to epidemiological data
      extracted from EHRs are an opportunity that must be seized as soon as possible.
      Our article addresses certain design and organizational aspects so that the
      technical requirements for such use are integrated into regional platforms in
      France. The article will base itself on organization of the Rhone-Alpes regional
      health platform. DISCUSSION: Different tools being deployed in France allow us to
      consider the potential of these regional platforms for epidemiology and public
      health (implementation of a national health identification number and a national
      information system interoperability framework). The deployment of the Rhone-Alpes
      regional health platform began in the 2000s in France. By August 2011, 2.6
      million patients were identified in this platform. A new development step is
      emerging because regional decision-makers need to measure healthcare efficiency.
      To pool heterogeneous information contained in various independent databases, the
      format, norm and content of the metadata have been defined. Two types of
      databases will be created according to the nature of the data processed, one for
      extracting structured data, and the second for extracting non-structured and de
      identified free-text documents. SUMMARY: Regional platforms for managing EHRs
      could constitute an important data source for epidemiological surveillance in the
      context of epidemic alerts, but also in monitoring a number of indicators of
      infectious and chronic diseases for which no data are yet available in France.

PMID- 22471903
TI  - Misfolded SOD1 and ALS: zeroing in on mitochondria.
AB  - Mutations in SOD1, causative for a subset of familial ALS cases, are associated
      with the formation of non-normal SOD1 conformers. Recent studies have defined
      this pool of SOD1 as misfolded and new antibodies have been developed to
      selectively detect misfolded SOD1 in vivo and in vitro. We will review these new
      tools and expand on the evidence demonstrating mitochondria as a common
      intersecting point for misfolded SOD1.

PMID- 22471904
TI  - ALSUntangled 15: coconut Oil.

PMID- 22471905
TI  - Transport and pharmacodynamics of albitiazolium, an antimalarial drug candidate.
AB  - BACKGROUND AND PURPOSE: Choline analogues, a new type of antimalarials, exert
      potent in vitro and in vivo antimalarial activity. This has given rise to
      albitiazolium, which is currently in phase II clinical trials to cure severe
      malaria. Here we dissected its mechanism of action step by step from choline
      entry into the infected erythrocyte to its effect on phosphatidylcholine (PC)
      biosynthesis. EXPERIMENTAL APPROACH: We biochemically unravelled the transport
      and enzymatic steps that mediate de novo synthesis of PC and elucidated how
      albitiazolium enters the intracellular parasites and affects the PC biosynthesis.
      KEY RESULTS: Choline entry into Plasmodium falciparum-infected erythrocytes is
      achieved both by the remnant erythrocyte choline carrier and by parasite-induced
      new permeability pathways (NPP), while parasite entry involves a poly-specific
      cation transporter. Albitiazolium specifically prevented choline incorporation
      into its end-product PC, and its antimalarial activity was strongly antagonized
      by choline. Albitiazolium entered the infected erythrocyte mainly via a
      furosemide-sensitive NPP and was transported into the parasite by a poly-specific
      cation carrier. Albitiazolium competitively inhibited choline entry via the
      parasite-derived cation transporter and also, at a much higher concentration,
      affected each of the three enzymes conducting de novo synthesis of PC.
      CONCLUSIONS AND IMPLICATIONS: Inhibition of choline entry into the parasite
      appears to be the primary mechanism by which albitiazolium exerts its potent
      antimalarial effect. However, the pharmacological response to albitiazolium
      involves molecular interactions with different steps of the de novo PC
      biosynthesis pathway, which would help to delay the development of resistance to
      this drug.

PMID- 22471907
TI  - Tunable spin-orbit interaction in trilayer graphene exemplified in electric
      double-layer transistors.
AB  - Taking advantage of ultrahigh electric field generated in electric-double-layer
      transistors (EDLTs), we investigated spin-orbit interaction (SOI) and its
      modulation in epitaxial trilayer graphene. It was found in magnetotransport that
      the dephasing length L(phi) and spin relaxation length L(so) of carriers can be
      effectively modulated with gate bias. As a direct result, SOI-induced weak
      antilocalization (WAL), together with a crossover from WAL to weak localization
      (WL), was observed at near-zero magnetic field. Interestingly, among existing
      localization models, only the Iordanskii-Lyanda-Geller-Pikus theory can
      successfully reproduce the obtained magnetoconductance well, serving as evidence
      for gate tuning of the weak but distinct SOI in graphene. Realization of SOI and
      its large tunability in the trilayer graphene EDLTs provides us with a
      possibility to electrically manipulate spin precession in graphene systems
      without ferromagnetics.

PMID- 22471906
TI  - Pharmacogenetic markers of CYP2B6 associated with efavirenz plasma concentrations
      in HIV-1 infected Thai adults.
AB  - AIMS: To investigate the frequency of CYP2B6 polymorphisms and the influence of
      haplotype structure on plasma efavirenz concentrations in Thai adults with HIV-1
      infection. METHODS: Genotyping of nine single nucleotide polymorphisms (SNPs,
      c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T, g.3003T>C,
      g.18492C>T and g.21563C>T) of CYP2B6 were performed using real-time PCR-based
      allelic discrimination on blood samples from 52 HIV-infected adults who had
      received an efavirenz-based regimen. Plasma efavirenz concentrations were
      measured by high performance liquid chromatography. RESULTS: The minor allele
      frequencies for c.64C>T, c.516G>T, c.785A>G, g.3003C>T, g.18492T>C and g.21563C>T
      were 0.087, 0.365, 0.413, 0.308 and 0.356, respectively. However, no variant
      alleles were identified for three SNPs (c.499 C>G, c.1375 A>G and c.1459 C>T).
      Efavirenz plasma concentrations were significantly associated with c.516G>T (P=
      0.0095), c.785A>G (P= 0.0017), g.21563C>T (P= 0.0036) and g.18492C>T (P= 0.0011).
      The composite CYP2B6 of three SNPs (c.516G >= T, c.785A >= G and g.21563C >= T)
      genotypes were significantly associated with higher efavirenz concentrations.
      CONCLUSIONS: Our data indicate that the GAC-CYP2B6 haplotype is associated with
      higher plasma efavirenz concentrations in HIV-infected Thai adults.

PMID- 22471908
TI  - Screening of cannabis-related problems among youth: the CPQ-A-S and CAST
      questionnaires.
AB  - BACKGROUND: Cannabis use among young people is a significant problem, making
      particularly necessary validated screening instruments that permit secondary
      prevention. The purpose of this study was to analyze and compare the psychometric
      properties of the CAST and CPQ-A-S questionnaires, two screening instruments
      specifically addressing the youth population. METHODS: Information was obtained
      on sociodemographics, frequency of substance use, psychopathological symptoms and
      cannabis-use problems, and the CPQ-A-S and CAST were applied, as well as an
      infrequency scale for discarding responses made randomly. The sample was made up
      of 144 young people aged 16 to 20 that had used cannabis in the last month, of
      which 71.5% were boys. Mean age of the sample was 17.38 years (SD = 1.16).
      RESULTS: The results show that from the psychometric point of view both the CAST
      and the CPQ-A-S are good screening instruments. CONCLUSIONS: The CAST is shorter
      and presents slightly better internal consistency than the CPQ-A-S. Both
      instruments show high sensitivity and specificity in the detection of young
      people dependent on cannabis according to the DSM IV-TR criteria. The CPQ-A-S
      appears to show greater capacity for detecting psychopathological distress
      associated with use. Both questionnaires yield significant odds ratios as
      predictors of frequent cannabis use and of the DSM IV-TR abuse and dependence
      criteria. In general, the CPQ-A-S emerges as a better predictor than the CAST.

PMID- 22471909
TI  - Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous
      neoplasms in Muir-Torre syndrome.
AB  - BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal-dominant disorder
      characterized by the association of sebaceous tumors or keratoacanthomas with an
      early onset visceral cancer in the spectrum of Lynch syndrome. OBSERVATIONS: A
      total of 20 sebaceous tumors including 18 sebaceous adenoma and two sebaceomas of
      six patients with MTS were analysed. Two main clinico-dermoscopic features were
      observed: (1) clinically pink to white papules/nodules with a central crater,
      dermoscopically characterized by radially arranged, elongated crown vessels
      surrounding opaque structureless yellow areas at times covered by blood crusts (n
      = 13) and (2), clinically pink to yellow papules/nodules without a central
      crater, dermoscopically exhibiting a few, loosely arranged yellow comedo-like
      globules and branching arborizing vessels (n = 7). Confocal microscopy was
      available in three sebaceous adenomas and revealed a good histopathologic
      correlation; sebaceous lobules were composed by clusters of ovoid cells with dark
      nuclei and bright, highly refractile glistening cytoplasm. They were delimited by
      a rim of epithelial cells, corresponding to basaloid cells. CONCLUSIONS: A better
      characterization of clinical, dermoscopic and confocal microscopy features of
      sebaceous tumors may improve their recognition and consequently, aid to rise the
      suspect for MTS.

PMID- 22471910
TI  - Bone formation rather than inflammation reflects ankylosing spondylitis activity
      on PET-CT: a pilot study.
AB  - INTRODUCTION: Positron Emission Tomography - Computer Tomography (PET-CT) is an
      interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity
      using specific PET tracers. Previous studies have shown that the PET tracers
      [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid
      arthritis (RA) and may therefore be useful in AS. Another interesting tracer for
      AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the
      potential of PET-CT in imaging AS activity was tested using different tracers,
      with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference.
      METHODS: In a stepwise approach different PET tracers were investigated. First,
      whole body [18F]FDG and [11C](R)PK11195 PET-CT scans were obtained of ten AS
      patients fulfilling the modified New York criteria. According to the BASDAI five
      of these patients had low and five had high disease activity. Secondly, an extra
      PET-CT scan using [18F]Fluoride was made of two additional AS patients with high
      disease activity. MRI scans of the total spine and sacroiliac joints were
      performed, and conventional radiographs of the total spine and sacroiliac joints
      were available for all patients. Scans and radiographs were visually scored by
      two observers blinded for clinical data. RESULTS: No increased [18F]FDG and
      [11C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In
      contrast, MRI demonstrated a total of five bone edema lesions in three out of 10
      patients. In the two additional AS patients scanned with [18F]Fluoride PET-CT,
      [18F]Fluoride depicted 17 regions with increased uptake in both vertebral column
      and sacroiliac joints. In contrast, [18F]FDG depicted only three lesions, with an
      uptake of five times lower compared to [18F]Fluoride, and again no
      [11C](R)PK11195 positive lesions were found. In these two patients, MRI detected
      nine lesions and six out of nine matched with the anatomical position of
      [18F]Fluoride uptake. Conventional radiographs showed structural bony changes in
      11 out of 17 [18F]Fluoride PET positive lesions. CONCLUSIONS: Our PET-CT data
      suggest that AS activity is reflected by bone activity (formation) rather than
      inflammation. The results also show the potential value of PET-CT for imaging AS
      activity using the bone tracer [18F]Fluoride. In contrast to active RA,
      inflammation tracers [18F]FDG and [11C](R)PK11195 appeared to be less useful for
      AS imaging.

PMID- 22471911
TI  - Familial reactive perforating collagenosis in a child: response to narrow-band
      UVB.
AB  - A favorable response to narrow-band ultraviolet B light treatment, a novel
      option, is illustrated in familial reactive perforating collagenosis, and its use
      is recommended. Its probable mode of action is outlined. 

PMID- 22471912
TI  - Peer-assisted learning in teaching clinical examination to junior medical
      students.
AB  - BACKGROUND: In medical education, peer-assisted learning (PAL) refers to teaching
      occurring between fellow students. Few descriptions of its use to teach clinical
      examination have been published. Student Grand Rounds (SGR) is a student-led
      initiative whereby senior students volunteer to teach clinical examination to pre
      clinical peers. Student tutors attend a modified Teaching on the Run (TOTR)
      course originally designed to train clinicians to teach students and junior
      doctors. AIM: We investigated the value of SGR in teaching pre-clinical students,
      and evaluated the effectiveness of TOTR. METHODS: Over 9 months, tutors and
      participants in each SGR tutorial completed an online survey. At the conclusion
      of annual TOTR workshops (2004-2010), participants evaluated their impressions of
      the course. RESULTS: A total of 64 SGR tutorials were attended by a total of 321
      students. All agreed that tutorials were beneficial and enjoyable, with a
      threefold increase in the number of students self-identifying as able to perform
      the skills required. TOTR participants classified the course as both relevant and
      beneficial, and all course outcomes were achieved. SGR tutors reported improved
      knowledge and confidence in teaching following SGR and TOTR. CONCLUSION: PAL is
      effective in supplementing teaching of clinical examination. Senior students
      learn valuable skills and gain experience in teaching.

PMID- 22471913
TI  - Twelve tips for incorporating educational theory into teaching practices.
AB  - BACKGROUND: Although there is no single overarching theory of learning, there is
      a group of learning theories that shares some common elements which can provide
      useful guidance on a range of teaching and learning practices. AIM: This article
      aims to describe Constructivist, Experiential and Humanistic learning theories,
      to explain how these three theories are fundamentally related and to demonstrate
      how each of them suggests teaching and learning practices. CONCLUSION: Common
      educational theories can be combined to provide 12 practical tips for teachers
      and facilitators. This demonstrates how theoretical ideas lead to practical
      consequences.

PMID- 22471914
TI  - Improving postgraduate clinical assessment tools: the introduction of video
      recordings to assess decision making.
AB  - BACKGROUND: Competency in the management of acutely unwell patients has not
      previously been formally assessed as part of an objective structured clinical
      examination (OSCE). AIM: The reliability of the paediatric postgraduate OSCE was
      calculated. An objective structured video examination was designed to assess
      candidates' clinical decision making ability when managing acutely unwell
      children. METHODS: The performance of 3522 postgraduate paediatric trainees was
      assessed (2006-2008). OSCE reliability was determined using Cronbach's alpha and
      mean inter-item correlation. Performance in the video station was compared with
      overall performance (not including video station; Mann-Whitney U) and video
      station scores correlated with individual station scores (Spearman's Rho
      correlation coefficient). RESULTS: Clinical examination pass rates for the 684 UK
      graduates, 1608 overseas candidates training in the UK and 1104 overseas
      candidates training overseas were 69.7%, 28% and 22.3%, respectively (graduation
      information not available for 126 candidates). Cronbach's alpha was 0.62. Mean
      inter-item correlation was 0.15. Candidates who passed the OSCE overall had
      significantly higher scores on the video station (t(3520) = 14.48); p < 0.001).
      There was significant positive correlation between scores on the video station,
      individual stations and overall total score (r's = 0.300; p = 0.001).
      CONCLUSIONS: The postgraduate paediatric OSCE provides a sound and valid means of
      assessing clinical skills at the postgraduate level. The video station provides
      an important new method of assessment. Its use in other postgraduate clinical
      examinations should be explored.

PMID- 22471915
TI  - Learning how to break bad news--more than following the rules.

PMID- 22471916
TI  - The Dundee Ready Education Environment Measure (DREEM): a review of its adoption
      and use.
AB  - BACKGROUND: The Dundee Ready Education Environment Measure (DREEM) was published
      in 1997 as a tool to evaluate educational environments of medical schools and
      other health training settings and a recent review concluded that it was the most
      suitable such instrument. AIMS: This study aimed to review the settings and
      purposes to which the DREEM has been applied and the approaches used to analyse
      and report it, with a view to guiding future users towards appropriate
      methodology. METHOD: A systematic literature review was conducted using the Web
      of Knowledge databases of all articles reporting DREEM data between 1997 and 4
      January 2011. RESULTS: The review found 40 publications, using data from 20
      countries. DREEM is used in evaluation for diagnostic purposes, comparison
      between different groups and comparison with ideal/expected scores. A variety of
      non-parametric and parametric statistical methods have been applied, but their
      use is inconsistent. CONCLUSIONS: DREEM has been used internationally for
      different purposes and is regarded as a useful tool by users. However, reporting
      and analysis differs between publications. This lack of uniformity makes
      comparison between institutions difficult. Most users of DREEM are not
      statisticians and there is a need for informed guidelines on its reporting and
      statistical analysis.

PMID- 22471917
TI  - Simple truths from medical students: perspectives on the quality of clinical
      learning environments.
AB  - BACKGROUND: The opportunity for students to learn whilst in a clinical placement
      is a central component of undergraduate medical education and an educationally
      conducive clinical environment is essential if the student is to optimise
      learning opportunities. AIM: This study, which was conducted by medical students,
      and amongst medical students aims to investigate the key conditions that students
      most value when placed in clinical settings. METHODS: A qualitative approach was
      adopted in which a series of focus group discussions were conducted by senior
      medical students trained in the facilitation of focus group moderation. In total,
      30 students contributed to four separate focus groups. RESULTS: Whilst students
      identified some factors which were similar to previous studies, other factors
      considered important to learning in the clinical setting surfaced. Namely, the
      need for students to be self-motivated and the valuable contribution that other
      medical students can make to the learning of their peers. CONCLUSIONS: Our
      findings concur with other similar studies. However, our findings were generated
      by medical students and not subject to influence by university teachers during
      the data collection and analysis. This not only serves to reinforce previous
      studies but also supports the use of peer data collection from medical students.

PMID- 22471918
TI  - Team-based learning: a relevant strategy in health professionals' education.
AB  - For about a decade, team-based learning (TBL), as an educational strategy, has
      been growing in use in the US and in several other international medical schools.
      It is a learner-centered, small group instructional strategy with good academic
      outcomes and considerable potential to address many of the professional
      competencies that are critical for the practice of medicine. For it to be
      successful in a course or curriculum, its essential components must be used
      properly. This article explains the importance and relevance of TBL in healthcare
      education, supports its inclusion as an effective learning strategy, and
      encourages the reader to explore additional resources, including the recently
      published AMEE Guide in Medical Education related to the topic (Parmelee et al,
      2012).

PMID- 22471919
TI  - Extracurricular participation in research and audit by medical students:
      opportunities, obstacles, motivation and outcomes.
AB  - BACKGROUND: Medical students should learn to critically evaluate research to
      inform future evidence-based practice. Participation in research and audit at
      medical school can help develop these skills whilst prompting interest in
      academic pursuits. AIMS: We investigate medical student attitudes and
      participation in extracurricular research and audit focusing on their
      opportunities, obstacles, motivation and outcomes. METHOD: A 60-item
      questionnaire was distributed to final-year medical students graduating from the
      University of Nottingham Medical School in the United Kingdom. RESULTS: A total
      of 238 questionnaires were returned (response rate 75%). Of these, 86% felt
      research or audit experience was useful for medical students. The main driver for
      involvement was curriculum vitae (CV) improvement (51%). Male students and those
      involved in extracurricular research were more likely to agree that this
      experience should influence selection into training programmes (p = 0.017, p =
      0.0036). Overall, 91 respondents (38%) had been involved in such activity with a
      mean number of projects undertaken of two (range one to four). Those interested
      in a surgical career were most likely to have undertaken projects (58%).
      Frequently cited obstacles to involvement were time constraints (74%) and a
      perceived lack of interest from potential supervisors (63%). CONCLUSIONS: Despite
      significant CV motivation, many are enthusiastic regarding extracurricular
      research opportunities but frustrated by obstacles faced. Our study suggests
      there is scope for providing further opportunities to participate in such
      activities at medical school.

PMID- 22471920
TI  - Ethnopharmacological use of plants by Sisala traditional healers in northwest
      Ghana.
AB  - CONTEXT AND OBJECTIVE: The Sisala traditional healers of northwest Ghana have a
      rich ethnomedical tradition. The purpose of this study was to collect and analyse
      data on medicinal plants commonly used by Sisala traditional healers. METHODS: A
      total of 30 traditional healers were interviewed using a mixture of open- and
      closed-ended questionnaires after obtaining prior-informed consent. Plant
      materials of each species of medicinal plant mentioned being used were collected
      and processed as voucher specimens following standard ethnobotanical methods.
      RESULTS: The majority (65%) of traditional healers were males, age >= 38, and
      their knowledge about medicinal plants was acquired orally largely from their
      parents (81.3%). A total of 35 species of plants were reported used to treat 24
      diseases. Most (55%) of the plant materials were harvested from the bush and
      about half (54.8%) of the healers collected plant materials in the morning. Leaf
      (20%) and root (17.5%) plant materials were most commonly used in the preparation
      of 27 herbal remedies for treatments. The modes of administration of the herbal
      remedies were both through internal and external routes. CONCLUSION: The results
      of this study show that Sisala traditional healers possess rich traditional
      knowledge about medicinal plants and new therapeutic use claims for 34 medicinal
      plants used in Ghana and widely within Africa are documented for the first time.

PMID- 22471921
TI  - Description of a multicenter safety checklist for intraoperative hemorrhage
      control while clamped during robotic partial nephrectomy.
AB  - BACKGROUND: The adoption of robotic assistance has contributed to the increased
      utilization of partial nephrectomy for the management of renal tumors. However,
      partial nephrectomy can be technically challenging because of intraoperative
      hemorrhage, which limits the ability to identify the tumor margin and may
      necessitate the conversion to open surgery or radical nephrectomy. To our
      knowledge, a comprehensive safety checklist does not exist to guide surgeons on
      the management of hemorrhage during robotic partial nephrectomy. We developed
      such an safety checklist based on the cumulative experiences of high volume
      robotic surgeons. METHODS: A treatment safety checklist for the management of
      hemorrhage during robotic partial nephrectomy was collaboratively developed based
      on prior experiences with intraoperative hemorrhage during robotic partial
      nephrectomy. RESULTS: Reducing the risk of hemorrhage during robotic partial
      nephrectomy begins with reviewing the preoperative imaging for renal vasculature
      and tumor anatomy, with a focus on accessory vessels and renal tumor proximity to
      the renal hilum. During hilar exposure, an attempt is made to identify additional
      accessory renal arteries. The decision is then made on whether to clamp the hilum
      (artery +/- vein). If bleeding is encountered during resection, management is
      based on whether the bleeding is suspected to be arterial or from venous
      backbleeding. Operative maneuvers that may increase the chance of success are
      highlighted in safety checklists for arterial and venous bleeding. CONCLUSIONS:
      Safely performing robotic partial nephrectomy is dependent on attention to
      prevention of hemorrhage and rapid response to the challenge of intraoperative
      bleeding. Preparation is essential for maximizing the chance of success during
      robotic partial nephrectomy.

PMID- 22471922
TI  - Androgen receptor expression predicts breast cancer survival: the role of genetic
      and epigenetic events.
AB  - BACKGROUND: Breast cancer outcome, including response to therapy, risk of
      metastasis and survival, is difficult to predict using currently available
      methods, highlighting the urgent need for more informative biomarkers. Androgen
      receptor (AR) has been implicated in breast carcinogenesis however its potential
      to be an informative biomarker has yet to be fully explored. In this study, AR
      protein levels were determined in a cohort of 73 Grade III invasive breast ductal
      adenocarcinomas. METHODS: The levels of Androgen receptor protein in a cohort of
      breast tumour samples was determined by immunohistochemistry and the results were
      compared with clinical characteristics, including survival. The role of defects
      in the regulation of Androgen receptor gene expression were examined by mutation
      and methylation screening of the 5' end of the gene, reporter assays of the 5'
      and 3' end of the AR gene, and searching for miRNAs that may regulate AR gene
      expression. RESULTS: AR was expressed in 56% of tumours and expression was
      significantly inversely associated with 10-year survival (P = 0.004). An
      investigation into the mechanisms responsible for the loss of AR expression
      revealed that hypermethylation of the AR promoter is associated with loss of AR
      expression in breast cancer cells but not in primary breast tumours. In AR
      negative breast tumours, mutation screening identified the same mutation (T105A)
      in the 5'UTR of two AR negative breast cancer patients but not reported in the
      normal human population. Reporter assay analysis of this mutation however found
      no evidence for a negative impact on AR 5'UTR activity. The role of miR-124 in
      regulating AR expression was also investigated, however no evidence for this was
      found. CONCLUSION: This study highlights the potential for AR expression to be an
      informative biomarker for breast cancer survival and sets the scene for a more
      comprehensive investigation of the molecular basis of this phenomenon.

PMID- 22471923
TI  - Mildly reduced graphene oxide-Ag nanoparticle hybrid films for surface-enhanced
      Raman scattering.
AB  - Large-area mildly reduced graphene oxide (MR-GO) monolayer films were self
      assembled on SiO2/Si surfaces via an amidation reaction strategy. With the MR-GO
      as templates, MR-GO-Ag nanoparticle (MR-GO-Ag NP) hybrid films were synthesized
      by immersing the MR-GO monolayer into a silver salt solution with sodium citrate
      as a reducing agent under UV illumination. SEM image indicated that Ag NPs with
      small interparticle gap are uniformly distributed on the MR-GO monolayer. Raman
      spectra demonstrated that the MR-GO monolayer beneath the Ag NPs can effectively
      quench the fluorescence signal emitted from the Ag films and dye molecules under
      laser excitation, resulting in a chemical enhancement (CM). The Ag NPs with
      narrow gap provided numerous hot spots, which are closely related with
      electromagnetic mechanism (EM), and were believed to remarkably enhance the Raman
      signal of the molecules. Due to the co-contribution of the CM and EM effects as
      well as the coordination mechanism between the MR-GO and Ag NPs, the MR-GO-Ag NP
      hybrid films showed more excellent Raman signal enhancement performance than that
      of either Ag films or MR-GO monolayer alone. This will further enrich the
      application of surface-enhanced Raman scattering in molecule detection.

PMID- 22471924
TI  - Determinants of linear growth from infancy to school-aged years: a population
      based follow-up study in urban Amazonian children.
AB  - BACKGROUND: Although linear growth during childhood may be affected by early-life
      exposures, few studies have examined whether the effects of these exposures
      linger on during school age, particularly in low- and middle-income countries.
      METHODS: We conducted a population-based longitudinal study of 256 children
      living in the Brazilian Amazon, aged 0.1 y to 5.5 y in 2003. Data regarding
      socioeconomic and maternal characteristics, infant feeding practices,
      morbidities, and birth weight and length were collected at baseline of the study
      (2003). Child body length/height was measured at baseline and at follow-up visits
      (in 2007 and 2009). Restricted cubic splines were used to construct average
      height-for-age Z score (HAZ) growth curves, yielding estimated HAZ differences
      among exposure categories at ages 0.5 y, 1 y, 2 y, 5 y, 7 y, and 10 y. RESULTS:
      At baseline, median age was 2.6 y (interquartile range, 1.4 y-3.8 y), and mean
      HAZ was -0.53 (standard deviation, 1.15); 10.2% of children were stunted. In
      multivariable analysis, children in households above the household wealth index
      median were 0.30 Z taller at age 5 y (P = 0.017), and children whose families
      owned land were 0.34 Z taller by age 10 y (P = 0.023), when compared with poorer
      children. Mothers in the highest tertile for height had children whose HAZ were
      significantly higher compared with those of children from mothers in the lowest
      height tertile at all ages. Birth weight and length were positively related to
      linear growth throughout childhood; by age 10 y, children weighing >3500 g at
      birth were 0.31 Z taller than those weighing 2501 g to 3500 g (P = 0.022) at
      birth, and children measuring >=51 cm at birth were 0.51 Z taller than those
      measuring <=48 cm (P = 0.005). CONCLUSIONS: Results suggest socioeconomic
      background is a potentially modifiable predictor of linear growth during the
      school-aged years. Maternal height and child's anthropometric characteristics at
      birth are positively associated with HAZ up until child age 10 y.

PMID- 22471925
TI  - Fournier gangrene and unexpected death.
AB  - Fournier gangrene represents a rare but progressive perineal infection that may
      result in rapid death. A 70-year-old man with poorly controlled diabetes mellitus
      and alcohol abuse is reported who was found unexpectedly dead. He had last been
      contacted the night before his death. At autopsy, the most striking finding was
      deep necrotic ulceration of the scrotum with exposure of underlying deep muscles
      and testicles, with blood cultures positive for Escherichia coli. Death was,
      therefore, attributed to necrotic ulceration/gangrene of the perineum (Fournier
      gangrene) that was due to E. coli sepsis with underlying contributing factors of
      diabetes mellitus and alcoholism. In addition there was morbid obesity (body mass
      index 46.9), cirrhosis of the liver, and marked focal coronary artery
      atherosclerosis with significant cardiomegaly. Fournier gangrene may be an
      extremely aggressive condition that can result in rapid death, as was
      demonstrated by the rapid progression in the reported case.

PMID- 22471926
TI  - Permitted water pollution discharges and population cancer and non-cancer
      mortality: toxicity weights and upstream discharge effects in US rural-urban
      areas.
AB  - BACKGROUND: The study conducts statistical and spatial analyses to investigate
      amounts and types of permitted surface water pollution discharges in relation to
      population mortality rates for cancer and non-cancer causes nationwide and by
      urban-rural setting. Data from the Environmental Protection Agency's (EPA)
      Discharge Monitoring Report (DMR) were used to measure the location, type, and
      quantity of a selected set of 38 discharge chemicals for 10,395 facilities across
      the contiguous US. Exposures were refined by weighting amounts of chemical
      discharges by their estimated toxicity to human health, and by estimating the
      discharges that occur not only in a local county, but area-weighted discharges
      occurring upstream in the same watershed. Centers for Disease Control and
      Prevention (CDC) mortality files were used to measure age-adjusted population
      mortality rates for cancer, kidney disease, and total non-cancer causes. Analysis
      included multiple linear regressions to adjust for population health risk
      covariates. Spatial analyses were conducted by applying geographically weighted
      regression to examine the geographic relationships between releases and
      mortality. RESULTS: Greater non-carcinogenic chemical discharge quantities were
      associated with significantly higher non-cancer mortality rates, regardless of
      toxicity weighting or upstream discharge weighting. Cancer mortality was higher
      in association with carcinogenic discharges only after applying toxicity weights.
      Kidney disease mortality was related to higher non-carcinogenic discharges only
      when both applying toxicity weights and including upstream discharges. Effects
      for kidney mortality and total non-cancer mortality were stronger in rural areas
      than urban areas. Spatial results show correlations between non-carcinogenic
      discharges and cancer mortality for much of the contiguous United States,
      suggesting that chemicals not currently recognized as carcinogens may contribute
      to cancer mortality risk. The geographically weighted regression results suggest
      spatial variability in effects, and also indicate that some rural communities may
      be impacted by upstream urban discharges. CONCLUSIONS: There is evidence that
      permitted surface water chemical discharges are related to population mortality.
      Toxicity weights and upstream discharges are important for understanding some
      mortality effects. Chemicals not currently recognized as carcinogens may
      nevertheless play a role in contributing to cancer mortality risk. Spatial models
      allow for the examination of geographic variability not captured through the
      regression models.

PMID- 22471927
TI  - Differential epidural block predicts the success of visceral block in patients
      with chronic visceral abdominal pain.
AB  - BACKGROUND AND AIMS: Differential thoracic epidural regional block, also known as
      a differential neural block (DNB), involves the placement of an epidural catheter
      placed in the thoracic epidural space to achieve appropriate anesthesia in a
      dermatomal distribution. This is a retrospective case series evaluating how well
      a DNB may predict success of subsequent visceral blockade in patients with
      chronic abdominal pain of visceral origin. METHODS: Of 402 patients who had a DNB
      performed for unexplained abdominal pain from January 2000 to January 2009, 81
      patients were found to have results consistent with visceral pain and thus
      underwent subsequent visceral blockade. Basic demographic data, years of chronic
      pain, history of psychosocial issues, initial visual analog scale (VAS) pain
      score, pain location, and medication usage were documented in our electronic
      medical record database. Parameters regarding DNB and visceral blocks also were
      documented. Descriptive statistics were computed for all variables. The positive
      predictive value (PPV) for DNB for whom visceral block was successful (at least a
      50% reduction in VAS) was calculated. Additionally, subjects with successful
      visceral blocks were compared to those with unsuccessful visceral blocks.
      PARTICIPANTS: All patients with chronic abdominal pain with normal
      gastrointestinal studies who underwent DNB. SETTING: Tertiary Outpatient Pain
      Management Clinic. DESIGN:   Retrospective Cohort Study. RESULTS: Mean age of
      patients was 46 (+/- 15) years, 73% were female, and median duration of pain was
      5 years. 67% of subjects were taking opioid analgesics. PPV of DNB was 70.4%.
      Only factor found to be statistically significant with visceral block success was
      baseline VAS with higher scores associated with DNB predictive success (6.8 +/-
      1.7 vs. 5.5, 1.8; P = 0.004). Use of membrane stabilizing medications was
      significantly more common in subjects for whom visceral block was not successful
      (46% vs. 25%; P = 0.058). Area underneath curve (AUC) for VAS was found to be
      0.70 (95% CI: 0.57, 0.82), which signifies fair discrimination. CONCLUSION:
      Differential neural block is fairly predictive of subsequent visceral block
      success in patients with chronic abdominal pain of visceral origin. An initial
      VAS >= 5 provides a sensitivity of 93%, which implies that VAS < 5 may predict
      unsuccessful visceral block. Contrarily, a value of >= 8 would provide a
      specificity of 92% and may be used to predict success of subsequent visceral
      block.

PMID- 22471928
TI  - A longitudinal study of the establishment and proliferation of Enterococcus on a
      dairy farm.
AB  - Enterococci are Gram-positive, facultative anaerobic cocci. They are found in
      many environments (including milk and dairy products, vegetables, plants,
      cereals, and meats). Enterococci are considered commensal organisms, but can also
      be opportunistic pathogens associated with morbidity and mortality of humans and
      animals. A longitudinal study of antibiotic resistance of Enterococcus to
      ampicillin, erythromycin, and tetracycline was conducted on an academic teaching
      farm. Environmental samples were collected by drag swabs at select locations
      prior to and after the introduction of livestock. All samples were initially
      processed and screened with specialized media, and then replica plated on tryptic
      soy agar containing a predetermined amount of antibiotic. There was some
      variation in the quantity of bacterial and antibiotic-resistant colonies;
      however, resistance to tetracycline was extremely high. The increases of too
      numerous to count populations were not time-dependent and appeared consistently
      after the placement of cows. There is little information on the prevalence and
      epidemiology of antibiotic resistance of Enterococci outside of the hospital
      setting, including on dairy farms. Longitudinal studies are important in
      providing insight into the dynamics of establishment and proliferation of
      bacteria and of antibiotic resistance.

PMID- 22471929
TI  - Microbiological surveillance of a bovine raw milk farm through multiplex real
      time PCR.
AB  - Raw milk is increasingly appreciated by consumers but can be contaminated by a
      variety of zoonotic pathogens. Therefore, preventive measures, such as on-farm
      hazard analysis critical control point (HACCP) programs, must be applied to
      protect consumers. The aim of the present study was the comparison of a multiplex
      real-time polymerase chain reaction (PCR) assay with a culture-based approach in
      an on-farm quality assurance program for the detection of Escherichia coli O157,
      Salmonella spp., and Listeria monocytogenes in bulk tank milk, in-line milk
      filters, manure, and feces. Results revealed that the real-time PCR was more
      sensitive in detecting E. coli O157 than the culture method in filters (48% vs.
      4% positive), manure (93% vs. 7% positive) and feces (60% vs. 4% positive). The
      two methods were equally efficient in detecting L. monocytogenes (8% of filters),
      while Salmonella spp. was not detected in any sample. In conclusion, the real
      time PCR, by reducing analysis time to two working days, can be proposed as a
      useful tool in the raw milk primary production setting as a rapid and user
      friendly screening method.

PMID- 22471930
TI  - Relation between gelation conditions and the physical properties of whey protein
      particles.
AB  - Whey protein particles have several applications in modulating food structure and
      for encapsulation, but there is a lack of methods to prepare particles with a
      very high internal protein content. In this study whey protein particles with
      high internal protein content were prepared through emulsification and heat
      gelation of 25% (w/w) whey protein isolate solution at different pH (6.8 or 5.5)
      and NaCl concentrations (50, 200, or 400 mM). Particles formed at pH 6.8 were
      spherical, whereas those formed at pH 5.5 were irregular and had a cauliflower
      like appearance. Both particles had an average size of few micrometers, and the
      particles formed at pH 5.5 had higher protein content (~39% w/v) than the
      particles formed at pH 6.8 (~18% w/v). Similarly, particle morphology and protein
      density were also affected by initial NaCl concentration: particles formed at 50
      mM NaCl (pH 6.8) were spherical, whereas particles formed at either 200 mM NaCl
      (pH 6.7) or 400 mM NaCl (pH 6.6) were irregular and protein density of the
      particles increased with increasing initial NaCl concentration. Whey protein
      particles formed at pH 5.5 showed an excellent heat stability: viscosity of the
      suspensions containing approximately 30% of protein particles formed at pH 5.5
      did not show any change after heating at 90  degrees C for 30 min while the
      viscosity of suspensions containing protein particles prepared at other
      conditions increased after heating. In summary, whey protein particles with
      varying microstructure, shape, internal protein density, and heat stability can
      be formed by using heat-induced gelation of whey protein isolate at different
      gelling conditions. 

PMID- 22471931
TI  - Two barriers for sodium in vascular endothelium?
AB  - Vascular endothelium plays a key role in blood pressure regulation. Recently, it
      has been shown that a 5% increase of plasma sodium concentration (sodium excess)
      stiffens endothelial cells by about 25%, leading to cellular dysfunction. Surface
      measurements demonstrated that the endothelial glycocalyx (eGC), an anionic
      biopolymer, deteriorates when sodium is elevated. In view of these results, a two
      barrier model for sodium exiting the circulation across the endothelium is
      suggested. The first sodium barrier is the eGC which selectively buffers sodium
      ions with its negatively charged proteoglycans. The second sodium barrier is the
      endothelial plasma membrane which contains sodium channels. Sodium excess, in the
      presence of aldosterone, leads to eGC break-down and, in parallel, to an up
      regulation of plasma membrane sodium channels. The following hypothesis is
      postulated: Sodium excess increases vascular sodium permeability. Under such
      conditions (e.g. high-sodium diet), day-by-day ingested sodium, instead of being
      readily buffered by the eGC and then rapidly excreted by the kidneys, is
      distributed in the whole body before being finally excreted. Gradually, the
      sodium overload damages the organism.

PMID- 22471933
TI  - Weekend admission to hospital has a higher risk of death in the elective setting
      than in the emergency setting: a retrospective database study of national health
      service hospitals in England.
AB  - BACKGROUND: Although acute hospitals offer a twenty-four hour seven day a week
      service levels of staffing are lower over the weekends and some health care
      processes may be less readily available over the weekend. Whilst it is thought
      that emergency admission to hospital on the weekend is associated with an
      increased risk of death, the extent to which this applies to elective admissions
      is less well known. We investigated the risk of death in elective and elective
      patients admitted over the weekend versus the weekdays. METHODS: Retrospective
      statistical analysis of routinely collected acute hospital admissions in England,
      involving all patient discharges from all acute hospitals in England over a year
      (April 2008-March 2009), using a logistic regression model which adjusted for a
      range of patient case-mix variables, seasonality and admission over a weekend
      separately for elective and emergency (but excluding zero day stay emergency
      admissions discharged alive) admissions. RESULTS: Of the 1,535,267 elective
      admissions, 91.7% (1,407,705) were admitted on the weekday and 8.3% (127,562)
      were admitted on the weekend. The mortality following weekday admission was 0.52%
      (7,276/1,407,705) compared with 0.77% (986/127,562) following weekend admission.
      Of the 3,105,249 emergency admissions, 76.3% (2,369,316) were admitted on the
      weekday and 23.7% (735,933) were admitted on the weekend. The mortality following
      emergency weekday admission was 6.53% (154,761/2,369,316) compared to 7.06%
      (51,922/735,933) following weekend admission. After case-mix adjustment, weekend
      admissions were associated with an increased risk of death, especially in the
      elective setting (elective Odds Ratio: 1.32, 95% Confidence Interval 1.23 to
      1.41); vs emergency Odds Ratio: 1.09, 95% Confidence Interval 1.05 to 1.13).
      CONCLUSIONS: Weekend admission appears to be an independent risk factor for dying
      in hospital and this risk is more pronounced in the elective setting. Given the
      planned nature of elective admissions, as opposed to the unplanned nature of
      emergency admissions, it would seem less likely that this increased risk in the
      elective setting is attributable to unobserved patient risk factors. Further work
      to understand the relationship between weekend processes of care and mortality,
      especially in the elective setting, is required.

PMID- 22471932
TI  - Ginsenoside-Rp1 inhibits platelet activation and thrombus formation via impaired
      glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation.
AB  - BACKGROUND AND PURPOSE: Ginsenosides are the main constituents for the
      pharmacological effects of Panax ginseng. Such effects of ginsenosides including
      cardioprotective and anti-platelet activities have shown stability and
      bioavailability limitations. However, information on the anti-platelet activity
      of ginsenoside-Rp1 (G-Rp1), a stable derivative of ginsenoside-Rg3, is scarce. We
      examined the ability of G-Rp1 to modulate agonist-induced platelet activation.
      EXPERIMENTAL APPROACH: G-Rp1 in vitro and ex vivo effects on agonist-induced
      platelet-aggregation, granule-secretion, [Ca(2+) ](i)  mobilization, integrin
      alpha(IIb) beta(3)  activation were examined. Vasodilator-stimulated
      phosphoprotein (VASP) and MAPK expressions and levels of tyrosine phosphorylation
      of the glycoprotein VI (GPVI) signalling pathway components were also studied. G
      Rp1 effects on arteriovenous shunt thrombus formation in rats or tail bleeding
      time and ex vivo coagulation time in mice were determined. KEY RESULT: G-Rp1
      markedly inhibited platelet aggregation induced by collagen, thrombin or ADP.
      While G-Rp1 elevated cAMP levels, it dose-dependently suppressed collagen-induced
      ATP-release, thromboxane secretion, p-selectin expression, [Ca(2+) ](i) 
      mobilization and alpha(IIb) beta(3)  activation and attenuated p38(MAPK)  and
      ERK2 activation. Furthermore, G-Rp1 inhibited tyrosine phosphorylation of
      multiple components (Fyn, Lyn, Syk, LAT, PI3K and PLCgamma2) of the GPVI
      signalling pathway. G-Rp1 inhibited in vivo thrombus formation and ex vivo
      platelet aggregation and ATP secretion without affecting tail bleeding time and
      coagulation time, respectively. CONCLUSION AND IMPLICATIONS: G-Rp1 inhibits
      collagen-induced platelet activation and thrombus formation through modulation of
      early GPVI signalling events, and this effect involves VASP stimulation, and ERK2
      and p38(-MAPK)  inhibition. These data suggest that G-Rp1 may have therapeutic
      potential for the treatment of cardiovascular diseases involving aberrant
      platelet activation.

PMID- 22471934
TI  - Transplanted bone marrow cells do not provide new oocytes but rescue fertility in
      female mice following treatment with chemotherapeutic agents.
AB  - It is generally accepted that mammalian females are born with a finite pool of
      oocytes and that this is the sole source of ovules throughout the reproductive
      life of the adult. This dogma was shaken in 2003 when researchers showed that the
      oocyte stock might be renewable in adult mammals. It has been proposed that
      hematopoietic stem cells might be a source of new oocytes. These discoveries have
      puzzled many researchers and remain controversial. In our study, we attempted to
      determine if transplanted bone marrow cells could provide new oocytes in PU.1
      mice and in severe combined immunodeficiency (SCID) mice after treatment with
      chemotherapeutic agents. We also examined the possibility that grafted bovine
      embryonic ovarian cortex might provide an environment favoring such a response.
      We found no evidence that transplanted bone marrow cells provide new fertilizable
      oocytes in PU.1 mice, in SCID mice treated with chemotherapeutic agents, or with
      bovine embryonic ovarian tissue grafts. However, transplanted bone marrow cells
      have improved the fertility of SCID mice previously treated with chemotherapeutic
      agents. These data suggest that bone marrow cells cannot provide new oocytes but
      can positively influence ovarian physiology to improve the fertility of mice
      previously treated with chemotherapeutic agents.

PMID- 22471935
TI  - Regioselective enzymatic carboxylation of phenols and hydroxystyrene derivatives.
AB  - The enzymatic carboxylation of phenol and styrene derivatives using
      (de)carboxylases in carbonate buffer proceeded in a highly regioselective
      fashion: Benzoic acid (de)carboxylases selectively formed o-hydroxybenzoic acid
      derivatives, phenolic acid (de)carboxylases selectively acted at the beta-carbon
      atom of styrenes forming (E)-cinnamic acids.

PMID- 22471936
TI  - Biopharmaceutical potential of lichens.
AB  - CONTEXT: Lichens are composite organisms consisting of a symbiotic association of
      a fungus (the mycobiont) with a photosynthetic partner (the phytobiont), usually
      either a green alga or cyanobacterium. The morphology, physiology and
      biochemistry of lichens are very different from those of the isolated fungus and
      alga in culture. Lichens occur in some of the most extreme environments on the
      Earth and may be useful to scientists in many commercial applications. OBJECTIVE:
      Over the past 2 decades, there has been a renewed and growing interest in lichens
      as a source of novel, pharmacologically active biomolecules. This review
      summarizes the past and current research and development trends in the
      characterization and use of lichens and their bioactive compounds in traditional
      medicine and other biopharmaceutical applications of commercial interest.
      METHODS: The present review contains 10 illustrations and 188 references compiled
      from major databases including Science Direct, Chemical Abstracts, PubMed and
      Directory of Open Access Journals. RESULTS: Lichen morphology, symbiosis,
      diversity and bioactivities including enzyme inhibitory, antimicrobial,
      antifungal, antiviral, anticancer, anti-insecticidal and antioxidant actions were
      reviewed and summarized. Recent progress in lichens and lichen-forming fungi was
      discussed with emphasis on their potential to accelerate commercialization of
      lichen-based products. CONCLUSIONS: Lichens are an untapped source of biological
      activities of industrial importance and their potential is yet to be fully
      explored and utilized. Lichen-derived bioactive compounds hold great promise for
      biopharmaceutical applications as antimicrobial, antioxidant and cytotoxic agents
      and in the development of new formulations or technologies for the benefit of
      human life.

PMID- 22471937
TI  - The guideline implementability research and application network (GIRAnet): an
      international collaborative to support knowledge exchange: study protocol.
AB  - BACKGROUND: Modifying the format and content of guidelines may facilitate their
      use and lead to improved quality of care. We reviewed the medical literature to
      identify features desired by different users and associated with guideline use to
      develop a framework of implementability and found that most guidelines do not
      contain these elements. Further research is needed to develop and evaluate
      implementability tools. METHODS: We are launching the Guideline Implementability
      Research and Application Network (GIRAnet) to enable the development and testing
      of implementability tools in three domains: Resource Implications,
      Implementation, and Evaluation. Partners include the Guidelines International
      Network (G-I-N) and its member guideline developers, implementers, and
      researchers. In phase one, international guidelines will be examined to identify
      and describe exemplar tools. Indication-specific and generic tools will populate
      a searchable repository. In phase two, qualitative analysis of cognitive
      interviews will be used to understand how developers can best integrate
      implementability tools in guidelines and how health professionals use them for
      interpreting and applying guidelines. In phase three, a small-scale pilot test
      will assess the impact of implementability tools based on quantitative analysis
      of chart-based behavioural outcomes and qualitative analysis of interviews with
      participants. The findings will be used to plan a more comprehensive future
      evaluation of implementability tools. DISCUSSION: Infrastructure funding to
      establish GIRAnet will be leveraged with the in-kind contributions of
      collaborating national and international guideline developers to advance our
      knowledge of implementation practice and science. Needs assessment and evaluation
      of GIRAnet will provide a greater understanding of how to develop and sustain
      such knowledge-exchange networks. Ultimately, by facilitating use of guidelines,
      this research may lead to improved delivery and outcomes of patient care.

PMID- 22471938
TI  - The effect of obesity on skin disease and epidermal permeability barrier status
      in children.
AB  - Obese adult patients have many dermatoses, such as skin tags, candida infection,
      cellulite, and intertrigo, but only limited data have been published on obese
      children and the barrier function of their skin. Sixty-five overweight and obese
      children (n = 40, BMI 85th-95th percentile; n = 25, BMI > 95th percentile) (aged
      8-15; mean age 11.6) and 30 normal-weight controls (aged 7-15; mean age 11.1)
      underwent a clinical evaluation and calculation of transepidermal water loss
      (TEWL). Higher weight percentile was associated with a higher incidence of some
      dermatoses. Skin tags were found in 40% of subjects in the 95th percentile and
      2.5% of those in the 85th percentile. Striae distensae were observed in 32% of
      patients in the 95th percentile and 22.5% of those in the 85th percentile.
      Plantar hyperkeratosis was observed only in 20% of the 95th percentile subjects
      and was not observed in the other groups. TEWL values at the forearm site were
      significantly higher (p < 0.05) in obese children than in the control group, but
      no significant differences in TEWL values according to BMI level were found
      between the two groups of obese children. Degree of obesity influences the
      incidence of some associated dermatoses; skin tags, striae distensae, and plantar
      hyperkeratosis were more frequent in children in the 95th percentile of BMI.
      Obesity increases the TEWL rate, suggesting that obese children might become more
      easily overheated as weight increases, with more profuse sweating because of the
      thick layers of subcutaneous fat.

PMID- 22471939
TI  - Human olfactory mucosa multipotent mesenchymal stromal cells promote survival,
      proliferation, and differentiation of human hematopoietic cells.
AB  - Multipotent mesenchymal stromal cells (MSCs) from the human olfactory mucosa (OM)
      are cells that have been proposed as a niche for neural progenitors. OM-MSCs
      share phenotypic and functional properties with bone marrow (BM) MSCs, which
      constitute fundamental components of the hematopoietic niche. In this work, we
      investigated whether human OM-MSCs may promote the survival, proliferation, and
      differentiation of human hematopoietic stem cells (HSCs). For this purpose, human
      bone marrow cells (BMCs) were co-cultured with OM-MSCs in the absence of
      exogenous cytokines. At different intervals, nonadherent cells (NACs) were
      harvested from BMC/OM-MSC co-cultures, and examined for the expression of blood
      cell markers by flow cytometry. OM-MSCs supported the survival (cell viability
      >90%) and proliferation of BMCs, after 54 days of co-culture. At 20 days of co
      culture, flow cytometric and microscopic analyses showed a high percentage (73%)
      of cells expressing the pan-leukocyte marker CD45, and the presence of cells of
      myeloid origin, including polymorphonuclear leukocytes, monocytes, basophils,
      eosinophils, erythroid cells, and megakaryocytes. Likewise, T (CD3), B (CD19),
      and NK (CD56/CD16) cells were detected in the NAC fraction. Colony-forming unit
      granulocyte/macrophage (CFU-GM) progenitors and CD34(+) cells were found, at 43
      days of co-culture. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      studies showed that OM-MSCs constitutively express early and late-acting
      hematopoietic cytokines (i.e., stem cell factor [SCF] and granulocyte- macrophage
      colony-stimulating factor [GM-CSF]). These results constitute the first evidence
      that OM-MSCs may provide an in vitro microenvironment for HSCs. The capacity of
      OM-MSCs to support the survival and differentiation of HSCs may be related with
      the capacity of OM-MSCs to produce hematopoietic cytokines.

PMID- 22471941
TI  - Team-based learning: a practical guide: AMEE guide no. 65.
AB  - Team-based learningTM (TBL) is an instructional strategy developed in the
      business school environment in the early 1990s by Dr Michaelsen who wanted the
      benefits of small group learning within large classes. In 2001, a US federal
      granting agency awarded funds for educators in the health sciences to learn about
      and implement the strategy in their educational programs; TBL was put forward as
      one such strategy and as a result it is used in over 60 US and international
      health science professional schools. TBL is very different from problem-based
      learning (PBL) and other small group approaches in that there is no need for
      multiple faculty or rooms, students must come prepared to sessions, and
      individual and small groups of students (teams) are highly accountable for their
      contributions to team productivity. The instructor must be a content-expert, but
      need not have any experience or expertise in group process to conduct a
      successful TBL session. Students do not need any specific instruction in teamwork
      since they learn how to be collaborative and productive in the process. TBL can
      replace or complement a lecture-based course or curriculum.

PMID- 22471940
TI  - Adipose tissue gene expression analysis reveals changes in inflammatory,
      mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant
      subjects.
AB  - BACKGROUND: To get insight into molecular mechanisms underlying insulin
      resistance, we compared acute in vivo effects of insulin on adipose tissue
      transcriptional profiles between obese insulin-resistant and lean insulin
      sensitive women. METHODS: Subcutaneous adipose tissue biopsies were obtained
      before and after 3 and 6 hours of intravenously maintained euglycemic
      hyperinsulinemia from 9 insulin-resistant and 11 insulin-sensitive females. Gene
      expression was measured using Affymetrix HG U133 Plus 2 microarrays and qRT-PCR.
      Microarray data and pathway analyses were performed with Chipster v1.4.2 and by
      using in-house developed nonparametric pathway analysis software. RESULTS: The
      most prominent difference in gene expression of the insulin-resistant group
      during hyperinsulinemia was reduced transcription of nuclear genes involved in
      mitochondrial respiration (mitochondrial respiratory chain, GO:0001934).
      Inflammatory pathways with complement components (inflammatory response,
      GO:0006954) and cytokines (chemotaxis, GO:0042330) were strongly up-regulated in
      insulin-resistant as compared to insulin-sensitive subjects both before and
      during hyperinsulinemia. Furthermore, differences were observed in genes
      contributing to fatty acid, cholesterol and triglyceride metabolism (FATP2,
      ELOVL6, PNPLA3, SREBF1) and in genes involved in regulating lipolysis (ANGPTL4)
      between the insulin-resistant and -sensitive subjects especially during
      hyperinsulinemia. CONCLUSIONS: The major finding of this study was lower
      expression of mitochondrial respiratory pathway and defective induction of lipid
      metabolism pathways by insulin in insulin-resistant subjects. Moreover, the study
      reveals several novel genes whose aberrant regulation is associated with the
      obese insulin-resistant phenotype.

PMID- 22471942
TI  - Exciplex electroluminescence and photoluminescence spectra of the new organic
      materials based on zinc complexes of sulphanylamino-substituted ligands.
AB  - We have investigated the electroluminescence spectra of the electroluminescent
      devices based on the new zinc complexes of amino-substituted benzothiazoles and
      quinolines containing the C-N-M-N chains in their chelate cycles. The spectra
      exhibit strong exciplex bands in the green to yellow region 540 to 590 nm due to
      interaction of the excited states of zinc complexes and triaryl molecules of the
      hole-transporting layer. For some devices, the intrinsic luminescence band of 460
      nm in the blue region is also observed along with the exciplex band giving rise
      to an almost white color of the device emission. The exciplex band can be
      eliminated if the material of the hole-transporting layer is not a triarylamine
      derivative. We have also found the exciplex emission in the photoluminescence
      spectra of the films containing blends of zinc complex and triphenylamine
      material.

PMID- 22471944
TI  - The association between body mass index and pulmonary thromboembolism in an
      autopsy population.
AB  - To evaluate the association between obesity and pulmonary thromboembolism (PTE)
      in a forensic context, 160 autopsy cases of fatal PTE were compared with age- and
      gender-matched controls. The mean age of cases was 66 years (range 26-98 years;
      M/F 74:86). The mean body mass index (BMI) of cases with PTE was 30.88 (range
      14.95-79.51), which was significantly higher than in the controls (mean BMI =
      25.33; range 12.49-61.84) (p < 0.0001). Comparing the group with PTE with
      controls showed that five (3.1%) compared to 20 (12.5%) were underweight, 39
      (24.4%) compared to 67 (41.88%) were of normal weight, 49 (30.63%) compared to 43
      (26.88%) were overweight, 43 (26.88%) compared to 24 (15%) were obese, and 24
      (15.0%) compared to six (3.75%) were morbidly obese. In each category of above
      normal BMIs, there were significantly greater numbers in the groups with PTE:
      overweight (p < 0.01), obese (p < 0.001), and morbidly obese (p < 0.0001).

PMID- 22471943
TI  - Hemoglobin levels and transfusions in neurocritically ill patients: a systematic
      review of comparative studies.
AB  - INTRODUCTION: Accumulating evidence suggests that, in critically ill patients, a
      lower hemoglobin transfusion threshold is safe. However, the optimal hemoglobin
      level and associated transfusion threshold remain unknown in neurocritically ill
      patients. METHODS: We conducted a systematic review of comparative studies
      (randomized and nonrandomized) to evaluate the effect of hemoglobin levels on
      mortality, neurologic function, intensive care unit (ICU) and hospital length of
      stay, duration of mechanical ventilation, and multiple organ failure in adult and
      pediatric neurocritically ill patients. We searched MEDLINE, The Cochrane Central
      Register of Controlled Trials, Embase, Web of Knowledge, and Google Scholar.
      Studies focusing on any neurocritical care conditions were included. Data are
      presented by using odds ratios for dichotomous outcomes and mean differences for
      continuous outcomes. RESULTS: Among 4,310 retrieved records, six studies met
      inclusion criteria (n = 537). Four studies were conducted in traumatic brain
      injury (TBI), one in subarachnoid hemorrhage (SAH), and one in a mixed population
      of neurocritically ill patients. The minimal hemoglobin levels or transfusion
      thresholds ranged from 7 to 10 g/dl in the lower-Hb groups and from 9.3 to 11.5
      g/dl in the higher-Hb groups. Three studies had a low risk of bias, and three had
      a high risk of bias. No effect was observed on mortality, duration of mechanical
      ventilation, or multiple organ failure. In studies reporting on length of stay (n
      = 4), one reported a significant shorter ICU stay (mean, -11.4 days (95%
      confidence interval, -16.1 to -6.7)), and one, a shorter hospital stay (mean, 
      5.7 days (-10.3 to -1.1)) in the lower-Hb groups, whereas the other two found no
      significant association. CONCLUSIONS: We found insufficient evidence to confirm
      or refute a difference in effect between lower- and higher-Hb groups in
      neurocritically ill patients. Considering the lack of evidence regarding long
      term neurologic functional outcomes and the high risk of bias of half the
      studies, no recommendation can be made regarding which hemoglobin level to target
      and which associated transfusion strategy (restrictive or liberal) to favor in
      neurocritically ill patients.

PMID- 22471945
TI  - Trends in absolute and relative educational inequalities in four modifiable
      ischaemic heart disease risk factors: repeated cross-sectional surveys from the
      Nord-Trondelag Health Study (HUNT) 1984-2008.
AB  - BACKGROUND: There has been an overall decrease in incident ischaemic heart
      disease (IHD), but the reduction in IHD risk factors has been greater among those
      with higher social position. Increased social inequalities in IHD mortality in
      Scandinavian countries is often referred to as the Scandinavian "public health
      puzzle". The objective of this study was to examine trends in absolute and
      relative educational inequalities in four modifiable ischaemic heart disease risk
      factors (smoking, diabetes, hypertension and high total cholesterol) over the
      last three decades among Norwegian middle-aged women and men. METHODS: Population
      based, cross-sectional data from The Nord-Trondelag Health Study (HUNT): HUNT 1
      (1984-1986), HUNT 2 (1995-1997) and HUNT 3 (2006-2008), women and men 40-59 years
      old. Educational inequalities were assessed using the Slope Index of Inequality
      (SII) and The Relative Index of Inequality (RII). RESULTS: Smoking prevalence
      increased for all education groups among women and decreased in men. Relative and
      absolute educational inequalities in smoking widened in both genders, with
      significantly higher absolute inequalities among women than men in the two last
      surveys. Diabetes prevalence increased in all groups. Relative inequalities in
      diabetes were stable, while absolute inequalities increased both among women (p =
      0.05) and among men (p = 0.01). Hypertension prevalence decreased in all groups.
      Relative inequalities in hypertension widened over time in both genders. However,
      absolute inequalities in hypertension decreased among women (p = 0.05) and were
      stable among men (p = 0.33). For high total cholesterol relative and absolute
      inequalities remained stable in both genders. CONCLUSION: Widening absolute
      educational inequalities in smoking and diabetes over the last three decades
      gives rise to concern. The mechanisms behind these results are less clear, and
      future studies are needed to assess if educational inequalities in secondary
      prevention of IHD are larger compared to educational inequalities in primary
      prevention of IHD. Continued monitoring of IHD risk factors at the population
      level is therefore warranted. The results emphasise the need for public health
      efforts to prevent future burdens of life-style-related diseases and to avoid
      further widening in socioeconomic inequalities in IHD mortality in Norway,
      especially among women.

PMID- 22471946
TI  - Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an
      invasive pancreatic cancer cell phenotype.
AB  - BACKGROUND: We have identified syndecan-2 as a protein potentially involved in
      perineural invasion of pancreatic adenocarcinoma (PDAC) cells. METHODS: Syndecan
      2 (SDC-2) expression was analyzed in human normal pancreas, chronic pancreatitis
      and PDAC tissues. Functional in vitro assays were carried out to determine its
      role in invasion, migration and signaling. RESULTS: SDC-2 was expressed in the
      majority of the tested pancreatic cancer cell lines while it was upregulated in
      nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC
      2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a
      peritumoral expression. Though SDC-2 silencing (using specific siRNA
      oligonucleotides) did not affect anchorage-dependent growth, it significantly
      reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4
      and Su8686. On the transcriptional level, migration-and invasion-associated genes
      were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K
      ras activity, phosphorylation of Src and--further downstream--phosphorylation of
      ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained
      unaltered. CONCLUSION: SDC-2 is a novel (perineural) invasion-associated gene in
      PDAC which cooperates with K-ras to induce a more invasive phenotype.

PMID- 22471947
TI  - Monitoring of patients treated with particle therapy using positron-emission
      tomography (PET): the MIRANDA study.
AB  - BACKGROUND: The purpose of this clinical study is to investigate the clinical
      feasibility and effectiveness of offline Positron-Emission-Tomography (PET)
      quality assurance for promoting the accuracy of proton and carbon ion beam
      therapy. METHODS/DESIGN: A total of 240 patients will be recruited, evenly
      sampled among different analysis groups including tumors of the brain, skull
      base, head and neck region, upper gastrointestinal tract including the liver,
      lower gastrointestinal tract, prostate and pelvic region. From the comparison of
      the measured activity with the planned dose and its corresponding simulated
      activity distribution, conclusions on the delivered treatment will be inferred
      and, in case of significant deviations, correction strategies will be elaborated.
      DISCUSSION: The investigated patients are expected to benefit from this study,
      since in case of detected deviations between planned and actual treatment
      delivery a proper intervention (e.g., correction) could be performed in a
      subsequent irradiation fraction. In this way, an overall better treatment could
      be achieved than without any in-vivo verification. Moreover, site-specific
      patient-population information on the precision of the ion range at HIT might
      enable improvement of the CT-range calibration curve as well as safe reduction of
      the treatment margins to promote enhanced treatment plan conformality and dose
      escalation for full clinical exploitation of the promises of ion beam therapy.
      TRIAL REGISTRATION: NCT01528670.

PMID- 22471948
TI  - Meta-analysis on the association between non-steroidal anti-inflammatory drug use
      and ovarian cancer.
AB  - AIM: Animal and in vitro studies suggest that the use of non-steroidal anti
      inflammatory drugs (NSAIDs) may be associated with reduced risk for ovarian
      cancer. However, results from these studies have been inconsistent. The aim of
      our study was to review and summarize the evidence provided by longitudinal
      studies on the association between NSAID use and ovarian cancer risk. METHODS: A
      comprehensive literature search for articles published up to December 2011 was
      performed. Prior to performing a meta-analysis, the studies were evaluated for
      publication bias and heterogeneity. Relative risk (RR) or odds ratios (OR) were
      calculated. RESULTS: Seventeen reports (13 case-control studies, one clinical
      trial and three cohort studies), published between 1998 and 2011 were identified.
      There was no evidence of an association between aspirin use and ovarian cancer
      risk based on a random-effects model (RR = 0.91, 95% confidence interval (CI)
      0.82, 1.01) or a fixed-effects model (RR = 0.94, 95% CI 0.87, 1.01). Similarly,
      we did not find strong evidence of an association between non-aspirin NSAID use
      and ovarian cancer using a random-effects model (RR = 0.89, 95% CI 0.74, 1.08) or
      a fixed-effects model (RR = 0.86, 95% CI 0.76, 0.98). Furthermore, our analysis
      did not show a strong association between frequency or duration of non-aspirin
      NSAID use and ovarian cancer. CONCLUSIONS: Our findings indicate that there is no
      strong evidence of an association between aspirin/NA-NSAID use and ovarian
      cancer. However, this subject deserves further investigation.

PMID- 22471949
TI  - Effects of topical tacrolimus 0.03% on long-term suberythemal ultraviolet B
      irradiated epidermal Langerhans cells in mice.

PMID- 22471950
TI  - Adsorption and solution properties of bottle-brush polyelectrolyte complexes:
      effect of molecular weight and stoichiometry.
AB  - Polyelectrolyte complexes (PECs) self-assembled from bottle-brush
      polyelectrolytes, having a cationic main chain and uncharged side chains, and
      linear anionic sodium polystyrenesulfonate (NaPSS) have been investigated with
      emphasis on (i) the charge density and side chain density of the bottle-brush
      polyelectrolyte, (ii) the molecular weight of NaPSS, and (iii) the charge
      stoichiometry of the mixture. Light scattering and electrophoretic mobility data
      demonstrate that small molecular complexes are formed when the PEO45 side chain
      density is sufficiently high to provide steric stabilization and prevent PEC
      aggregation. The adsorption of PECs on negatively charged silicon oxynitride was
      investigated using dual polarization interferometry, and the time evolution of
      the adsorbed amount and thickness was determined. Cationic, uncharged, and
      negatively charged complexes all adsorb to negatively charged silicon oxynitride,
      and maximum adsorption is achieved for positively charged complexes containing
      small amounts of PSS. The adsorbed amount and the kinetics of adsorption are
      reduced with increasing PSS content, and for any given stoichiometry with
      increasing PSS molecular weight. These findings are discussed in terms of the PEC
      structure and the ability of anionic polyelectrolytes to leave the PECs during
      adsorption. 

PMID- 22471951
TI  - Queensland Lung Cancer Screening Study: rationale, design and methods.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in
      Australia. Screening using low-dose computed tomography (LDCT) can reduce lung
      cancer mortality. The feasibility of screening in Australia is unknown. This
      paper describes the rationale, design and methods of the Queensland Lung Cancer
      Screening Study. AIMS: The aim of the study is to describe the methodology for a
      feasibility study of lung cancer screening by LDCT in Australia. METHODS: The
      Queensland Lung Cancer Screening Study is an ongoing, prospective observational
      study of screening by LDCT at a single tertiary institution. Healthy volunteers
      at high risk of lung cancer (age 60-74 years; smoking history >=30 pack years,
      current or quit within 15 years; forced expiratory volume in 1s >=50% predicted)
      are recruited from the general public through newspaper advertisement and press
      release. Participants receive a LDCT scan of the chest at baseline, year 1 and
      year 2 using a multidetector helical computed tomography scanner and are followed
      up for a total of 5 years. Feasibility of screening will be assessed by cancer
      detection rates, lung nodule prevalence, optimal management strategies for lung
      nodules, economic costs, healthcare utilisation and participant quality of life.
      CONCLUSIONS: Studying LDCT screening in the Australian setting will help us
      understand how differences in populations, background diseases and healthcare
      structures modulate screening effectiveness. This information, together with
      results from overseas randomised studies, will inform and facilitate local
      policymaking.

PMID- 22471952
TI  - The influence of age, gender and socio-economic status on multimorbidity patterns
      in primary care. First results from the multicare cohort study.
AB  - BACKGROUND: Multimorbidity is a phenomenon with high burden and high prevalence
      in the elderly. Our previous research has shown that multimorbidity can be
      divided into the multimorbidity patterns of 1) anxiety, depression, somatoform
      disorders (ADS) and pain, and 2) cardiovascular and metabolic disorders. However,
      it is not yet known, how these patterns are influenced by patient
      characteristics. The objective of this paper is to analyze the association of
      socio-demographic variables, and especially socio-economic status with
      multimorbidity in general and with each multimorbidity pattern. METHODS: The
      MultiCare Cohort Study is a multicentre, prospective, observational cohort study
      of 3.189 multimorbid patients aged 65+ randomly selected from 158 GP practices.
      Data were collected in GP interviews and comprehensive patient interviews.
      Missing values have been imputed by hot deck imputation based on Gower distance
      in morbidity and other variables. The association of patient characteristics with
      the number of chronic conditions is analysed by multilevel mixed-effects linear
      regression analyses. RESULTS: Multimorbidity in general is associated with age
      (+0.07 chronic conditions per year), gender (-0.27 conditions for female),
      education (-0.26 conditions for medium and -0.29 conditions for high level vs.
      low level) and income (-0.27 conditions per logarithmic unit). The pattern of
      cardiovascular and metabolic disorders shows comparable associations with a
      higher coefficient for gender (-1.29 conditions for female), while multimorbidity
      within the pattern of ADS and pain correlates with gender (+0.79 conditions for
      female), but not with age or socioeconomic status. CONCLUSIONS: Our study
      confirms that the morbidity load of multimorbid patients is associated with age,
      gender and the socioeconomic status of the patients, but there were no effects of
      living arrangements and marital status. We could also show that the influence of
      patient characteristics is dependent on the multimorbidity pattern concerned,
      i.e. there seem to be at least two types of elderly multimorbid patients. First,
      there are patients with mainly cardiovascular and metabolic disorders, who are
      more often male, have an older age and a lower socio-economic status. Second,
      there are patients mainly with ADS and pain-related morbidity, who are more often
      female and equally distributed across age and socio-economic groups. TRIAL
      REGISTRATION: ISRCTN89818205.

PMID- 22471953
TI  - Chondroprotective and anti-inflammatory role of melanocortin peptides in TNF
      alpha activated human C-20/A4 chondrocytes.
AB  - BACKGROUND AND PURPOSE: Melanocortin MC(1)  and MC(3 ) receptors, mediate the
      anti-inflammatory effects of melanocortin peptides. Targeting these receptors
      could therefore lead to development of novel anti-inflammatory therapeutic
      agents. We investigated the expression of MC(1)  and MC(3)  receptors on
      chondrocytes and the role of alpha-melanocyte-stimulating hormone (alpha-MSH) and
      the selective MC(3)  receptor agonist, [DTRP(8) ]-gamma-MSH, in modulating
      production of inflammatory cytokines, tissue-destructive proteins and induction
      of apoptotic pathway(s) in the human chondrocytic C-20/A4 cells. EXPERIMENTAL
      APPROACH: Effects of alpha-MSH, [DTRP(8) ]-gamma-MSH alone or in the presence of
      the MC(3/4)  receptor antagonist, SHU9119, on TNF-alpha induced release of pro
      inflammatory cytokines, MMPs, apoptotic pathway(s) and cell death in C-20/A4
      chondrocytes were investigated, along with their effect on the release of the
      anti-inflammatory cytokine IL-10. KEY RESULTS: C-20/A4 chondrocytes expressed
      functionally active MC(1,3)  receptors. alpha-MSH and [DTRP(8) ]-gamma-MSH
      treatment, for 30 min before TNF-alpha stimulation, provided a time-and-bell
      shaped concentration-dependent decrease in pro-inflammatory cytokines (IL-1beta,
      IL-6 and IL-8) release and increased release of the chondroprotective and anti
      inflammatory cytokine, IL-10, whilst decreasing expression of MMP1, MMP3, MMP13
      genes.alpha-MSH and [DTRP(8) ]-gamma-MSH treatment also inhibited TNF-alpha
      induced caspase-3/7 activation and chondrocyte death. The effects of [DTRP(8) ]
      gamma-MSH, but not alpha-MSH, were abolished by the MC(3/4)  receptor antagonist,
      SHU9119. CONCLUSION AND IMPLICATIONS: Activation of MC(1) /MC(3)  receptors in C
      20/A4 chondrocytes down-regulated production of pro-inflammatory cytokines and
      cartilage-destroying proteinases, inhibited initiation of apoptotic pathways and
      promoted release of chondroprotective and anti-inflammatory cytokines. Developing
      small molecule agonists to MC(1) /MC(3)  receptors could be a viable approach for
      developing chondroprotective and anti-inflammatory therapies in rheumatoid and
      osteoarthritis.

PMID- 22471954
TI  - Study protocol: using the Q-STEPS to assess and improve the quality of physical
      activity programmes for the elderly.
AB  - BACKGROUND: Aging is one of the most important and obvious phenomenon observed in
      our society. In the past years, there has been a growing concern in designing
      physical activity (PA) programmes for elderly people, because evidence suggests
      that such health promotion interventions may reduce the deleterious effects of
      the ageing process. Accordingly, a growing body of literature points to the
      importance of a sound approach to planning and evaluation in order to improve the
      quality of PA programmes. However, while numerous PA programmes have been
      designed for the elderly in recent years, their evaluation has been scarce.
      Quality management processes and tools provide a practical way for organisations
      to assess, identify and shed light on the areas requiring improvement. The
      Quality Self-assessment Tool for Exercise Programmes for Seniors (Q-STEPS) seems
      to provide a framework tailored to evaluate PA programmes for the elderly.
      FINDINGS: The primary purpose of this study is 1) to determine feasibility,
      acceptability and usability of the Q-STEPS. Secondary purposes of the study are:
      2) to examine the quality of the PA programmes for elderly people developed by
      the Portuguese Local Administration over a three-year period of self-assessments
      in terms of: a) Enabler domains (Leadership, Policy and Strategy, People,
      Partnership and Resources, Processes); b) Result domains (Customer Results,
      People Results, Society Results and Key Performance Results); 3) to estimate the
      association between the use of Q-STEPS and some indicators relating to the
      elderly participants, during the three self-assessments, such as: attendance
      rates, physical fitness, health-related quality of life and the elderly's
      perceived quality of the programme. The study will be conducted in PA programmes
      for elderly adults from mainland Portuguese municipalities over a three-year
      period. The project will adopt a participative quality improvement approach that
      features annual learning cycles of: 1) self-assessment with the Q-STEPS; 2)
      feedback to and interpretation of results involving programme's staff; 3) action
      planning to achieve system changes; 4) implementation of strategies for change;
      and 5) review process through further self-assessment. The study will collect a
      range of process and outcome data that will be used to achieve the research aims.
      DISCUSSION: It is our understanding that the results of the Q-STEPS study will
      contribute directly to the evidence based on effectiveness of continuous quality
      improvement approaches, in order to improve customer satisfaction and adherence
      to PA programmes targeting the ageing population. This comprehensive evaluation
      will also add significant new knowledge regarding the characteristics associated
      with a sustainable public service.

PMID- 22471955
TI  - Atopic dermatitis in African American children: addressing unmet needs of a
      common disease.
AB  - Recent published data suggest that the prevalence of atopic dermatitis (AD) in
      African American children is significantly higher than in Caucasians. There are
      certain characteristics in the presentation of AD in African Americans that seem
      to differ from those in other racial groups, but there is a paucity of
      information on this topic. In this review, we highlight the differences in
      pathophysiology, clinical presentation, and treatment of AD between African
      Americans and Caucasians. It is important for dermatologists to understand these
      differences in order to provide better care for African American children with
      AD.

PMID- 22471957
TI  - PPAR- gamma agonist in treatment of diabetes: cardiovascular safety
      considerations.
AB  - The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid
      receptors, which contain a type II zinc finger DNA binding motif and a
      hydrophobic ligand binding pocket. These receptors are thought to play an
      important role in metabolic diseases such as obesity, insulin resistance, and
      coronary artery disease. Three subtypes of PPAR receptors have been described:
      PPARalpha, PPARdelta/beta, and PPARgamma. PPARalpha is found in the liver,
      muscle, kidney, and heart. In the liver, its role is to up-regulate genes
      involved in fatty acid uptake, binding, beta-oxidation and electron transport,
      and oxidative phosphorylation in subcutaneous fat but not in skeletal muscle.
      PPARdelta/beta is expressed in many tissues but markedly in brain, adipose
      tissue, and skin. PPARgamma has high expression in fat, low expression in the
      liver, and very low expression in the muscle. The thiazolidinediones (TZD) are
      synthetic ligands of PPARgamma. By activating a number of genes in tissues,
      PPARgamma increases glucose and lipid uptake, increases glucose oxidation,
      decreases free fatty acid concentration, and decreases insulin resistance.
      Although, there is a rationale for the use of TZDs in patients with type 2
      diabetes mellitus, clinical studies have produced conflicting data. While
      currently used TZDs are clearly associated with heart failure (HF) worsening;
      with regards to cardiovascular outcomes, pioglitazone seems to be related to a
      trend toward reduction in cardiovascular morbidity and mortality, whereas
      rosiglitazone may actually increase risk of cardiovascular events. We review the
      existing literature on TZDs and discuss role and cardiovascular safety of these
      agents for the contemporary treatment of diabetes. Other side effects of these
      agents i.e. increase in osteoporosis and possible risk of bladder cancer is also
      discussed.

PMID- 22471956
TI  - Treating depression in coronary artery disease and chronic heart failure: what's
      new in using selective serotonin re-uptake inhibitors?
AB  - Depression is a common co-morbidity in patients with cardiovascular diseases such
      as chronic coronary artery disease, acute coronary syndromes, post by-pass
      surgery and chronic heart failure. The presence of depression is independently
      associated with a decline in health status and an increase in the risk of
      hospitalization and death for patients with coronary artery disease or congestive
      heart failure. Novel treatment modalities such as selective serotonin re-uptake
      inhibitors (SSRIs) may improve depressive symptoms and prognosis of post
      myocardial infarction and heart failure patients interacting with the common
      pathophysiological mechanisms of depression and cardiovascular disease. This
      review summarizes current experimental and clinical evidence regarding the
      effects of SSRIs on platelet functions, immune and neurohormonal activation, and
      cardiac rhythm disturbances in patients with cardiovascular disease.

PMID- 22471958
TI  - Complications after percutaneous endoscopic gastrostomy in a prospective study.
AB  - BACKGROUND: Insertion of a percutaneous endoscopic gastrostomy (PEG) is an
      increasingly common procedure in patients with nutritional needs and dysphagia.
      Better knowledge of rates and patterns of complications after PEG might influence
      decision-making. MATERIAL AND METHODS: The objective was to prospectively
      evaluate the rate of six pre-defined complications (leakage, diarrhea,
      constipation, abdominal pain, fever and peristomal infection) and mortality
      occurring within 2 months after PEG in an unselected sample of patients. All
      patients (n = 484) who had a PEG inserted at the hospital during the study period
      were included. Kaplan-Meier curves were used to estimate mortality over the first
      60 days following PEG and Fisher's exact test was used to test equality of
      proportions. RESULTS: Of the 484 patients included, 85 (18%) died within 2 months
      after PEG insertion. The risk of early mortality was higher in the group with
      neurological disease than in the group with a tumor as indication (p < 0.001).
      After excluding mortality, the overall complication rates at 2 weeks and 2 months
      were 39% and 27%, respectively. The most common complications within 2 weeks were
      abdominal pain (13%), peristomal infection (11%), diarrhea (11%) and leakage
      (10%). At 2 months the most frequent complications were diarrhea (10%), leakage
      (8%) and peristomal infection (6%). CONCLUSIONS: In the short-term perspective,
      there is a substantial risk of complications, including mortality, after PEG
      insertion. This should be considered during clinical decision-making and when
      informing the patients and caregivers.

PMID- 22471959
TI  - Effect of standardized extract of Marsilea minuta on learning and memory
      performance in rat amnesic models.
AB  - CONTEXT: Marsilea minuta Linn (Marsileaceae) is a common Indian hydrophytic
      plant. Traditionally, the plant has been used as a sedative for the treatment of
      insomnia and other mental disorders. Background information of this plant has
      encouraged us to investigate its antiamnesic activity in rat. OBJECTIVE:
      Standardized ethanol extract of M. minuta was investigated for their putative
      role in learning and memory performance in normal and amnesic rats. MATERIALS AND
      METHODS: Ethanol extract of M. minuta (EMM) was standardized for marsiline using
      HPLC. The effect of standardized extract of M. minuta (1.15% w/w marsiline) was
      tested in amnesic rat using elevated plus maze (EPM) and passive avoidance (PA)
      test. Amnesia was induced after scopolamine (1 mg/kg, s.c.) and electroconvulsive
      shock (150 mA, 0.2 s) treatment. Behavioral studies were further substantiated
      with acetylcholinesterase (AChE) activity and radioligand muscarinic receptor
      binding studies in rat brain regions. RESULTS: Oral administration of EMM at 200
      and 400 mg/kg/day for 3 days significantly reversed the amnesia whereas, no per
      se effect was observed. In comparison to control, AChE activity in frontal cortex
      and hippocampus was found to be significantly (P < 0.05) inhibited by EMM. EMM at
      doses 200 and 400 mg/kg has significantly (P < 0.05) increased (+34 % and +40 %
      change in affinity, respectively) the binding of 3H-QNB in frontal cortex
      indicating the up regulation of the muscarinic receptors. DISCUSSION AND
      CONCLUSION: These findings suggest that standardized extract of M. minuta have
      excellent antiamnesic activity, probably mediating through central cholinergic
      system.

PMID- 22471960
TI  - Association of smoking or tobacco use with ear diseases among men: a
      retrospective study.
AB  - BACKGROUND: Health related behaviour specially smoking and tobacco in any form
      are major determinants of health and lead to health inequities. Tobacco leads to
      various health problems including ear, nose and throat diseases. OBJECTIVE: To
      determine the influence of smoking or tobacco use on ear diseases we performed a
      retrospective study among men. METHOD: Of 11454 subjects of different age-groups
      there were 4143 men aged 20-60 years who were evaluated for demographic
      variables, smoking/tobacco use and middle and internal ear diseases. Descriptive
      statistics and age adjusted logistic regression analyses were performed. RESULTS:
      Among the 4143 men, 1739 (42.0%) were smokers or used tobacco. In smokers/tobacco
      users compared to non-users the age adjusted odds ratios and 95% confidence
      intervals (CI) for chronic suppurative otitis media were 1.13 (CI 0.96-1.34),
      acute otitis media 1.16 (CI 0.82-1.64), suppurative otitis media 1.21 (CI 0.79
      1.84), otosclerosis 0.97 (CI 0.52-1.33) (p > 0.05) and for overall middle ear
      diseases was 1.15 (CI 0.99-1.33, p = 0.05). For internal ear diseases the age
      adjusted odds ratios were for sensorineural hearing loss 1.12 (CI 0.92-1.58),
      0.12 (CI 0.42-0.93) for vertigo and tinnitus and overall internal ear diseases
      were 0.97 (CI 0.77-1.22, p = 0.81). Among men 40-60 years there was a
      significantly greater risk for both middle ear (OR 1.73, CI 1.29-2.30) and
      internal ear diseases (OR 1.94, CI 1.24-3.04) (p < 0.001). CONCLUSION:
      Smoking/tobacco use is significantly associated with greater prevalence of middle
      and internal ear diseases among middle-aged men in India.

PMID- 22471962
TI  - Growth and shrinkage of pluronic micelles by uptake and release of flurbiprofen:
      variation of pH.
AB  - The micellization of Pluronic triblock copolymers (P103, P123, and L43) in the
      presence of flurbiprofen at different pH was studied by small-angle neutron
      scattering (SANS), pulsed-field gradient stimulated-echo nuclear magnetic
      resonance (PFGSE-NMR), and surface tension measurements. Addition of flurbiprofen
      to the Pluronic at low pH leads to an increase in the fraction of micellization,
      aggregation number, and the core radius of the micelles. However, changing the pH
      to above the pKa of flurbiprofen in an ethanol/water mixture (~6.5) reduces the
      fraction of micellization and results in a weaker interaction between the drug
      and micelles due to the increased drug solubility in aqueous solution. 

PMID- 22471961
TI  - Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+ tumor
      infiltrating lymphocytes in ductal and lobular breast cancers.
AB  - BACKGROUND: Clinical relevance of tumor infiltrating lymphocytes (TILs) in breast
      cancer is controversial. Here, we used a tumor microarray including a large
      series of ductal and lobular breast cancers with long term follow up data, to
      analyze clinical impact of TIL expressing specific phenotypes and distribution of
      TILs within different tumor compartments and in different histological subtypes.
      METHODS: A tissue microarray (TMA) including 894 ductal and 164 lobular breast
      cancers was stained with antibodies recognizing CD4, FOXP3, and IL-17 by standard
      immunohistochemical techniques. Lymphocyte counts were correlated with clinico
      pathological parameters and survival. RESULTS: CD4(+) lymphocytes were more
      prevalent than FOXP3(+) TILs whereas IL-17(+) TILs were rare. Increased numbers
      of total CD4(+) and FOXP3(+) TIL were observed in ductal, as compared with
      lobular carcinomas. High grade (G3) and estrogen receptor (ER) negative ductal
      carcinomas displayed significantly (p < 0.001) higher CD4(+) and FOXP3(+)
      lymphocyte infiltration while her2/neu over-expression in ductal carcinomas was
      significantly (p < 0.001) associated with higher FOXP3(+) TIL counts. In
      contrast, lymphocyte infiltration was not linked to any clinico-pathological
      parameters in lobular cancers. In univariate but not in multivariate analysis
      CD4(+) infiltration was associated with significantly shorter survival in
      patients bearing ductal, but not lobular cancers. However, a FOXP3(+)/CD4(+)
      ratio > 1 was associated with improved overall survival even in multivariate
      analysis (p = 0.033). CONCLUSIONS: Ductal and lobular breast cancers appear to be
      infiltrated by different lymphocyte subpopulations. In ductal cancers increased
      CD4(+) and FOXP3(+) TIL numbers are associated with more aggressive tumor
      features. In survival analysis, absolute numbers of TILs do not represent major
      prognostic indicators in ductal and lobular breast cancer. Remarkably however, a
      ratio > 1 of total FOXP3(+)/CD4(+) TILs in ductal carcinoma appears to represent
      an independent favorable prognostic factor.

PMID- 22471963
TI  - An elaborate regulation of Mammalian target of rapamycin activity is required for
      somatic cell reprogramming induced by defined transcription factors.
AB  - The mammalian target of the rapamycin (mTOR) signaling pathway functions in many
      cellular processes, including cell growth, proliferation, differentiation, and
      survival. Recent advances have demonstrated that differentiated somatic cells can
      be directly reprogrammed into the pluripotent state by overexpression of several
      pluripotency transcription factors. However, whether the mTOR signaling pathway
      is involved in this somatic cell-reprogramming process remains unknown. Here, we
      provide evidence that an elaborate regulation of the mTOR activity is required
      for the successful reprogramming of somatic cells to pluripotency. The
      reprogramming of somatic cells collected from the Tsc2(-/-) embryo, in which the
      mTOR activity is hyperactivated, is entirely inhibited. By taking advantage of
      the secondary inducible pluripotent stem (iPS) system, we demonstrate that either
      elevating the mTOR activity by Tsc2 shRNA knockdown or using high concentrations
      of rapamycin to completely block the mTOR activity in cells derived from iPS mice
      greatly impairs somatic cell reprogramming. Secondary iPS induction efficiency
      can only be elevated by elaborately regulating the mTOR activity. Taken together,
      our data demonstrate that the precise regulation of the mTOR activity plays a
      critical role in the successful reprogramming of somatic cells to form iPS cells.

PMID- 22471964
TI  - Recent firing range suicides in South Australia.
AB  - Two cases are reported from South Australia, where deaths occurred that were due
      to single self-inflicted gunshot wounds to the head in individuals who were
      visiting indoor firearm ranges. Case 1: A 54-year-old man visiting an indoor
      firing range placed a .357 magnum handgun to his head and fired one shot. Case 2:
      A 23-year-old woman who was being instructed in firearm usage at an indoor firing
      range placed a 9 mm handgun to her head and fired one shot. In both cases, deaths
      were due to cerebral laceration with skull fracture. Firing ranges may be
      utilized by individuals who are seeking weapons for suicide attempts, and suicide
      may be successfully undertaken at such locations even while a victim is under
      direct supervision. In jurisdictions, where firearm ownership is strictly
      legislated, it may be that clubs can inadvertently provide access to firearms for
      this type of activity.

PMID- 22471965
TI  - An exploratory study to examine intentions to adopt an evidence-based HIV linkage
      to-care intervention among state health department AIDS directors in the United
      States.
AB  - BACKGROUND: Widespread dissemination and implementation of evidence-based human
      immunodeficiency virus (HIV) linkage-to-care (LTC) interventions is essential for
      improving HIV-positive patients' health outcomes and reducing transmission to
      uninfected others. To date, however, little work has focused on identifying
      factors associated with intentions to adopt LTC interventions among policy
      makers, including city, state, and territory health department AIDS directors who
      play a critical role in deciding whether an intervention is endorsed,
      distributed, and/or funded throughout their region. METHODS: Between December
      2010 and February 2011, we administered an online questionnaire with state,
      territory, and city health department AIDS directors throughout the United States
      to identify factors associated with intentions to adopt an LTC intervention.
      Guided by pertinent theoretical frameworks, including the Diffusion of
      Innovations and the "push-pull" capacity model, we assessed participants'
      attitudes towards the intervention, perceived organizational and contextual
      demand and support for the intervention, likelihood of adoption given endorsement
      from stakeholder groups (e.g., academic researchers, federal agencies, activist
      organizations), and likelihood of enabling future dissemination efforts by
      recommending the intervention to other health departments and community-based
      organizations. RESULTS: Forty-four participants (67% of the eligible sample)
      completed the online questionnaire. Approximately one-third (34.9%) reported that
      they intended to adopt the LTC intervention for use in their city, state, or
      territory in the future. Consistent with prior, related work, these participants
      were classified as LTC intervention "adopters" and were compared to "nonadopters"
      for data analysis. Overall, adopters reported more positive attitudes and greater
      perceived demand and support for the intervention than did nonadopters. Further,
      participants varied with their intention to adopt the LTC intervention in the
      future depending on endorsement from different key stakeholder groups. Most
      participants indicated that they would support the dissemination of the
      intervention by recommending it to other health departments and community-based
      organizations. CONCLUSIONS: Findings from this exploratory study provide initial
      insight into factors associated with public health policy makers' intentions to
      adopt an LTC intervention. Implications for future research in this area, as well
      as potential policy-related strategies for enhancing the adoption of LTC
      interventions, are discussed.

PMID- 22471966
TI  - Value of segmental myocardial strain by 2-dimensional strain echocardiography for
      assessment of scar area induced in a rat model of myocardial infarction.
AB  - OBJECTIVES: Two-dimensional strain echocardiography (2DSE) technique has enabled
      accurate quantification of regional myocardial function. This experimental study
      was aimed to investigate the value of 2DSE in detection of segmental regional
      myocardial dysfunction induced by fibrosis following myocardial infarction in a
      small animal (rat) model. METHODS: A rat model of myocardial infarction was
      established by ligation of the proximal left anterior descending coronary artery
      in 17 SD rats. Regional myocardial function was detected by 2DSE at baseline and
      4-weeks post-infarction, including end-systolic radial strain and strain rate (SR
      and SrR) and end-systolic circumferential strain and strain rate (SC and SrC) of
      each of six segments at papillary level. According to the size of scar found by
      histologic Masson staining, the optimal cutoff points of parameters for detecting
      scar area were analyzed and the sensitivity and specificity of every parameter to
      detect myocardial scar were obtained using ROC. RESULTS: (1) Comparing with
      parameters measured at baseline, there were significant decreases in SR, SrR, SC
      and SrC of each segment at 4 weeks post-infarction, with the worst in the infarct
      area (32.90 +/- 8.79 vs 11.18 +/- 3.89, 6.28 +/- 1.35 vs 3.18 +/- 0.47, -14.46 +/
      2.21 vs -6.30 +/- 2.17 and 4.93 +/- 0.95 vs 2.59 +/- 1.16, respectively) (all P
      < 0.05). (2)By 4 weeks, the myocardium of infarct area (anteroseptum, anterior
      and anterolateral) had fibrosis (31.33 +/- 9.89, 73.42 +/- 13.21 and 13.99 +/-
      3.24%, respectively) with minimal fibrosis in inferoseptal segment (0.32 +/-
      0.19%), no fibrosis was found in the inferior and inferolateral segments.
      (3)Significant negative correlations were found between the size of segmental
      scar and 2DSE parameters (r-value -0.61 ~ -0.80, all P < 0.01) with the strongest
      correlation in SR. SR less than 10% has 84% sensitivity and 98% specificity for
      detecting segments of scar area greater than 30% with AUC = 0.97. CONCLUSIONS:
      2DSE is able to assess regional myocardial dysfunction in a rat model of
      myocardial infarction and has high accuracy in detecting infarct segments with
      scar area greater than 30%.

PMID- 22471967
TI  - Antimicrobial characterization and safety aspects of the bacteriocinogenic
      Enterococcus hirae F420 isolated from Moroccan raw goat milk.
AB  - The F420 strain, isolated from raw goat milk and identified as Enterococcus
      hirae, was selected because of its strong activity against gram-positive
      bacteria, including Listeria monocytogenes. Interestingly, the F420 strain lacks
      the virulence genes and decarboxylase activity of histidine, lysine, and
      ornithine, and it is susceptible to 11 of 14 tested antibiotics, including
      vancomycin. The antimicrobial compounds produced by E. hirae F420 strain showed
      high resistance to heat treatment and to acidic and basic pHs. The MALDI-TOF mass
      spectrometry analysis coupled with the sequence of peptide and structural gene
      analysis of one of the purified enterocins showed 100% identity with enterocin P
      (EntP), previously described in E. faecium strains. The structural gene for EntP
      is located on a plasmid of 65 kb. Other enterocins with molecular mass higher
      than 7 kDa were also detected. This is the first report of the production of EntP
      by E. hirae species naturally occurring in foods. The biotechnological
      characteristics of the F420 strain and its enterocins indicate their potential
      for application in the control of L. monocytogenes and other undesirable bacteria
      in food systems.

PMID- 22471968
TI  - Proteomic analysis of Terminalia chebula extract-dependent changes in human
      lymphoblastic T cell protein expression.
AB  - Terminalia chebula is a native plant from southern Asia to southwestern China
      that is used in traditional medicine for the treatment of malignant tumors and
      diabetes. This plant also has antibacterial and immunomodulatory properties. The
      present study assessed T. chebula extract-dependent protein expression changes in
      Jurkat cells. Matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry and Ingenuity Pathways Analysis (IPA) were performed to assess
      protein expression and networks, respectively. A comparative proteomic profile
      was determined in T. chebula extract (50 MUg/mL)-treated and control cells; the
      expressions of beta-tubulin, ring finger and CHY zinc finger domain containing 1,
      and insulin-like growth factor 1 receptor kinase were significantly down
      regulated in T. chebula extract-treated Jurkat cells. Moreover, the molecular
      basis for the T. chebula extract-dependent protein expression changes in Jurkat
      cells was determined by IPA. Treatment with the T. chebula extract significantly
      inhibited nuclear factor-kappaB activity and affected the proteomic profile of
      Jurkat cells. The molecular network signatures and functional proteomics obtained
      in this study may facilitate the evaluation of potential antitumor therapeutic
      targets and elucidate the molecular mechanism of T. chebula extract-dependent
      effects in Jurkat cells.

PMID- 22471969
TI  - Auraptene attenuates gastritis via reduction of Helicobacter pylori colonization
      and pro-inflammatory mediator production in C57BL/6 mice.
AB  - Helicobacter pylori is a major human pathogen that plays central roles in chronic
      gastritis and gastric cancer. Recently, we reported that auraptene suppressed H.
      pylori adhesion via expression of CD74, which has been identified as a new
      receptor for H. pylori urease. In this study, we attempted to clarify the effects
      of oral feeding of auraptene on H. pylori infection and resultant inflammatory
      responses in C57BL/6 mice and found that it remarkably attenuated H. pylori
      colonization and gastritis. Biochemical analyses revealed that auraptene
      inhibited H. pylori-induced expression and/or production of CD74, macrophage
      migration inhibitory factor, interleukin-1beta, and tumor necrosis factor-alpha
      in gastric mucosa, together with serum macrophage inhibitory protein-2. It is
      notable that treatment with this coumarin during the pretreatment period was more
      effective than that during posttreatment. Our results suggest that auraptene is a
      promising phytochemical for reducing the risk of H. pylori-induced gastritis and
      carcinogenesis.

PMID- 22471970
TI  - Role of human papillomaviruses in persistent and glucocorticoid-resistant
      juvenile phimosis.
AB  - BACKGROUND: In adults, human papillomaviruses (HPV), lichen sclerosus et
      atrophicus (LSA) and phimosis are considered to be major risk factors for penile
      cancer. In boys, a possible association between phimosis, LSA and HPV has been
      suggested. OBJECTIVE: To investigate the role of HPV in the persistence of
      phimosis in children. PATIENTS AND METHODS: Out of a cohort of 420 boys
      presenting with foreskin problems, we prospectively sampled the preputial tissue
      of 82 patients during circumcision: 46 with steroid-naive and 36 with steroid
      resistant phimosis. All foreskins were assessed clinically and
      histopathologically with regard to appearance, inflammation, oedema, epithelial
      degeneration and fibrosis. The viral status of the foreskins was determined by
      immunohistochemistry and highly sensitive PCR, with subsequent subtyping by DNA
      hybridization (HPV types 6, 11, 16, 18, 31, 33, 35, 39, 42, 44, 45, 51-54, 56,
      58, 59, 61, 62, 66-68, 70, 72, 73, 81-84, 90, 91). RESULTS: The foreskins
      appeared normal in 62 boys and suggestive of LSA in one single case. Small cracks
      or white scars were present in seven steroid-naive and 12 steroid-resistant
      foreskins. LSA was diagnosed microscopically in two of the steroid-naive and six
      of the steroid-pretreated group. No evidence of HPV was found in any of the
      juvenile foreskins. CONCLUSIONS: Our prospective study has provided evidence that
      HPV is not usually present in the foreskin of boys with persistent phimosis after
      their first year of life and that topical glucocorticoid treatment failure is not
      associated with HPV or any specific histopathological changes.

PMID- 22471971
TI  - Lifestyle Triple P: a parenting intervention for childhood obesity.
AB  - BACKGROUND: Reversing the obesity epidemic requires the development and
      evaluation of childhood obesity intervention programs. Lifestyle Triple P is a
      parent-focused group program that addresses three topics: nutrition, physical
      activity, and positive parenting. Australian research has established the
      efficacy of Lifestyle Triple P, which aims to prevent excessive weight gain in
      overweight and obese children. The aim of the current randomized controlled trial
      is to assess the effectiveness of the Lifestyle Triple P intervention when
      applied to Dutch parents of overweight and obese children aged 4-8 years. This
      effectiveness study is called GO4fit. METHODS/DESIGN: Parents of overweight and
      obese children are being randomized to either the intervention or the control
      group. Those assigned to the intervention condition receive the 14-week Lifestyle
      Triple P intervention, in which they learn a range of nutritional, physical
      activity and positive parenting strategies. Parents in the control group receive
      two brochures, web-based tailored advice, and suggestions for exercises to
      increase active playing at home. Measurements are taken at baseline, directly
      after the intervention, and at one year follow-up. Primary outcome measure is the
      children's body composition, operationalized as BMI z-score, waist circumference,
      and fat mass (biceps and triceps skinfolds). Secondary outcome measures are
      children's dietary behavior and physical activity level, parenting practices,
      parental feeding style, parenting style, parental self-efficacy, and body
      composition of family members (parents and siblings). DISCUSSION: Our
      intervention is characterized by a focus on changing general parenting styles, in
      addition to focusing on changing specific parenting practices, as obesity
      interventions typically do. Strengths of the current study are the randomized
      design, the long-term follow-up, and the broad range of both self-reported and
      objectively measured outcomes. TRIAL REGISTRATION: Current Controlled Trials NTR
      2555 MEC AZM/UM: NL 31988.068.10 / MEC 10-3-052.

PMID- 22471972
TI  - Unmet needs of people with end-stage chronic obstructive pulmonary disease:
      recommendations for change in Australia.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an increasing cause
      of mortality. However, people with COPD are unlikely to receive care that meets
      the needs of themselves or their carers at the end of life. AIMS: To explore the
      needs of people with end-stage COPD in South Australia and develop
      recommendations for a model of care. METHODS: Three related studies were
      undertaken: in Study 1, 15 people with advanced COPD and their carers were
      interviewed twice, 6 months apart; Study 2 investigated views of an Expert Panel
      and Study 3 conducted focus groups and interviews with service providers and
      community groups to examine service availability and accessibility. RESULTS: This
      project demonstrated that the needs of people with COPD are not being met. There
      was an absence of a coordinated pathway for support. Care was fragmented,
      episodic and reactive. The role of carers was poorly recognised. Health
      professionals identified the lack of a clear transition to an end-stage and
      significant barriers to obtaining support for activities of daily living.
      Communication issues were identified in all studies, including the absence of
      advance care planning conversations. CONCLUSIONS: A flexible model of care is
      needed that assists people with COPD to navigate the health system. This should
      be patient centred and coordinated across primary, acute and community sectors.
      Neither respiratory nor palliative care services alone can adequately support
      people with COPD. The integration of a multidisciplinary palliative approach
      within a chronic disease management strategy will be central for the best care
      for people living with advanced COPD.

PMID- 22471973
TI  - Production of extracellular fatty acid using engineered Escherichia coli.
AB  - BACKGROUND: As an alternative for economic biodiesel production, the microbial
      production of extracellular fatty acid from renewable resources is receiving more
      concerns recently, since the separation of fatty acid from microorganism cells is
      normally involved in a series of energy-intensive steps. Many attempts have been
      made to construct fatty acid producing strains by targeting genes in the fatty
      acid biosynthetic pathway, while few studies focused on the cultivation process
      and the mass transfer kinetics. RESULTS: In this study, both strain improvements
      and cultivation process strategies were applied to increase extracellular fatty
      acid production by engineered Escherichia coli. Our results showed overexpressing
      'TesA and the deletion of fadL in E. coli BL21 (DE3) improved extracellular fatty
      acid production, while deletion of fadD didn't strengthen the extracellular fatty
      acid production for an undetermined mechanism. Moreover, the cultivation process
      controls contributed greatly to extracellular fatty acid production with respect
      to titer, cell growth and productivity by adjusting the temperature, adding
      ampicillin and employing on-line extraction. Under optimal conditions, the E.
      coli strain (pACY-'tesA-DeltafadL) produced 4.8 g L-1 extracellular fatty acid,
      with the specific productivity of 0.02 g h-1 g-1 dry cell mass, and the yield of
      4.4% on glucose, while the ratios of cell-associated fatty acid versus
      extracellular fatty acid were kept below 0.5 after 15 h of cultivation. The fatty
      acids included C12:1, C12:0, C14:1, C14:0, C16:1, C16:0, C18:1, C18:0. The
      composition was dominated by C14 and C16 saturated and unsaturated fatty acids.
      Using the strain pACY-'tesA, similar results appeared under the same culture
      conditions and the titer was also much higher than that ever reported previously,
      which suggested that the supposedly superior strain did not necessarily perform
      best for the efficient production of desired product. The strain pACY-'tesA could
      also be chosen as the original strain for the next genetic manipulations.
      CONCLUSIONS: The general strategy of metabolic engineering for the extracellular
      fatty acid production should be the cyclic optimization between cultivation
      performance and strain improvements. On the basis of our cultivation process
      optimization, strain improvements should be further carried out for the effective
      and cost-effective production process.

PMID- 22471975
TI  - From spirolactam mixtures to regioisomerically pure 5- and 6-rhodamines: a
      chemodosimeter-inspired strategy.
AB  - Inspired by the ring-open reaction of rhodamine spriolactams as typical
      chemodosimeters, a general strategy is proposed to conveniently and efficiently
      synthesize isomerically pure 5- and 6-R-tetramethylrhodamine on a larger scale.

PMID- 22471974
TI  - Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on
      benign prostatic hyperplasia.
AB  - BACKGROUND AND PURPOSE: Inflammation plays a key role in the development of
      benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5
      lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid
      is a novel flavonoid-based 'dual inhibitor' of the COX and 5-LOX enzymes. This
      study evaluated the effects of flavocoxid in experimental BPH. EXPERIMENTAL
      APPROACH: Rats were treated daily with testosterone propionate (3 mg.kg(-1) 
      s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone
      were randomized to receive vehicle (1 mL.kg(-1) , i.p.) or flavocoxid (20 mg.kg(
      1) , i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and
      protein levels for apoptosis-related proteins and growth factors were assayed in
      prostate tissue. The effects of flavocoxid were also tested on human prostate
      carcinoma PC3 cells. KEY RESULTS: Flavocoxid reduced prostate weight and
      hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the
      increased production of PGE(2)  and leukotriene B(4)  (LTB(4) ), enhanced pro
      apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA.
      Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid
      stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated
      induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in
      PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated
      apoptosis during prostatic growth. CONCLUSION AND IMPLICATIONS: Our results show
      that a 'dual inhibitor' of the COX and 5-LOX enzymes, such as flavocoxid, might
      represent a rational approach to reduce BPH through modulation of eicosanoid
      production and a caspase-induced apoptotic mechanism.

PMID- 22471977
TI  - Adsorption properties and degradation dynamics of endocrine-disrupting chemical
      levonorgestrel in soils.
AB  - Levonorgestrel, a synthetic progesterone used as an oral contraceptive or
      emergency contraceptive pill, has been shown to be an endocrine-disrupting
      chemical. To assess the environmental risk of levonorgestrel, batch experiments
      and laboratory microcosm studies were conducted to investigate the adsorption and
      degradation of levonorgestrel in five contrasting soils of China. Freundlich and
      Langmuir models were applied to sorption data to examine the affinity of
      levonorgestrel for soils with varying physical and chemical properties. The K(f)
      of levonorgestrel in the tested soils ranged from 10.79 to 60.92 mg(1-n) L(n) kg(
      1) with N between 0.69 and 1.23, and the Q(m) ranged from 18.18 to 196.08 mg/kg.
      The multiple regression analysis was conducted between K(f) and soil properties.
      Results indicate that total organic carbon plays a dominant role in the
      adsorption process. Gibbs free energy values less than 40 kJ/mol demonstrate that
      levonorgestrel sorption on soils could be considered as a physical adsorption.
      The degradation of levonorgestrel in five soils was fitted by the first-order
      reaction kinetics model. The half-lives of levonorgestrel were between 4.32 and
      11.55 days. The initial concentration and sterilization experiments illustrated
      that the degradation rate of levonorgestrel in soil was concentration-dependent
      and microbially mediated. The low mobility potential of levonorgestrel in soils
      was predicted by the groundwater ubiquity score (GUS) and retardation factor
      (R(f)).

PMID- 22471976
TI  - Establishment of a PCR analysis method for canine BRCA2.
AB  - BACKGROUND: Mammary tumors are the most common tumor type in both human and
      canine females. In women, carriers of mutations in BRCA2, a tumor suppressor gene
      product, have a higher risk of breast cancer. Canine BRCA2 has also been
      suggested to have a relationship with mammary tumors. However, clearly
      deleterious BRCA2 mutations have not been identified in any canine mammary
      tumors, as appropriate methods to detect mutations or a consensus BRCA2 sequence
      have not been reported. FINDINGS: For amplification and sequencing of BRCA2, we
      designed 14 and 20 PCR primer sets corresponding to the BRCA2 open reading frame
      (ORF) and all 27 exons, respectively, including exon-intron boundaries of the
      canine BRCA2 regions, respectively. To define the consensus canine BRCA2 ORF
      sequence, we used established methods to sequence the full-length canine BRCA2
      ORF sequence from two ovaries and a testis obtained from individual healthy
      mongrel dogs and partially sequence BRCA2 genomic sequences in 20-56 tumor-free
      dogs, each aged over 6 years. Subsequently, we compared these sequences and seven
      previously reported sequences, and defined the most common base sequences as the
      consensus canine BRCA2 ORF sequence. Moreover, we established a detection method
      for identifying splicing variants. Unexpectedly, we also identified novel
      splicing variants in normal testes during establishment of these methods.
      CONCLUSIONS: The present analysis methods for determining the BRCA2 base sequence
      and for detecting BRCA2 splicing variants and the BRCA2 ORF consensus sequence
      are useful for better understanding the relationship between canine BRCA2
      mutation status and cancer risk.

PMID- 22471978
TI  - Cadmium and its epigenetic effects.
AB  - Cadmium (Cd) is a toxic, nonessential transition metal and contributes a health
      risk to humans, including various cancers and cardiovascular diseases; however,
      underlying molecular mechanisms remain largely unknown. Cells transmit
      information to the next generation via two distinct ways: genetic and epigenetic.
      Chemical modifications to DNA or histone that alters the structure of chromatin
      without change of DNA nucleotide sequence are known as epigenetics. These
      heritable epigenetic changes include DNA methylation, post-translational
      modifications of histone tails (acetylation, methylation, phosphorylation, etc),
      and higher order packaging of DNA around nucleosomes. Apart from DNA
      methyltransferases, histone modification enzymes such as histone
      acetyltransferase, histone deacetylase, and methyltransferase, and microRNAs
      (miRNAs) all involve in these epigenetic changes. Recent studies indicate that Cd
      is able to induce various epigenetic changes in plant and mammalian cells in
      vitro and in vivo. Since aberrant epigenetics plays a critical role in the
      development of various cancers and chronic diseases, Cd may cause the above
      mentioned pathogenic risks via epigenetic mechanisms. Here we review the in vitro
      and in vivo evidence of epigenetic effects of Cd. The available findings indicate
      that epigenetics occurred in association with Cd induction of malignant
      transformation of cells and pathological proliferation of tissues, suggesting
      that epigenetic effects may play a role in Cd toxic, particularly carcinogenic
      effects. The future of environmental epigenomic research on Cd should include the
      role of epigenetics in determining long-term and late-onset health effects
      following Cd exposure.

PMID- 22471979
TI  - Editorial: Transthyretin: a small protein in the big world of amyloidoses.

PMID- 22471980
TI  - Diagnosis and therapeutic approaches to transthyretin amyloidosis.
AB  - Hereditary amyloidogenic transthyretin (TTR) (ATTR) amyloidosis is an autosomal
      dominant form of fatal hereditary amyloidosis. Owing to progress in biochemical
      and molecular genetic analyses, this disease is now believed to occur worldwide.
      As of today, reports of about 120 different points of single or double mutations,
      or a deletion in the TTR gene have been reported, and several different
      phenotypes of ATTR amyloidosis have been documented. In addition, since liver
      transplantation has been established to halt the progression of hereditary ATTR
      amyloidosis in the early stage, rapid and reliable diagnostic system for ATTR
      amyloidosis is needed. On the other hand, senile systemic amyloidosis (SSA)
      derived from wild-type (WT) TTR affects primarily in the heart and lungs and
      occasionally in carpal ligaments in the elderly. To perform accurate diagnosis
      and effective treatments, we should distinguish between hereditary ATTR
      amyloidosis and SSA by means of genetic and proteomic analyses. The liver
      transplantation for hereditary ATTR amyloidosis has become a well-established
      treatment, because the main source of serum variant TTR is shut out. However,
      this treatment has several problems, such as expensive medical costs, lifelong
      administration of immunosuppressants, non-indication for the mutated-TTR gene
      carriers without clinical symptoms, shortage of liver donors, and further
      development of cardiac and ocular disorders. Therefore, we and other ATTR
      amyloidosis research groups have been investigating the possibility of
      stabilization of variant TTR, gene therapy, and immunotherapy for ATTR
      amyloidosis on the basis of TTR amyloid formation mechanism. We present here the
      current diagnostic procedure and therapeutic approaches for the disease.

PMID- 22471981
TI  - Nearly 200 X-ray crystal structures of transthyretin: what do they tell us about
      this protein and the design of drugs for TTR amyloidoses?
AB  - Transthyretin (TTR), a beta-strand rich tetrameric protein present in human serum
      and cerebrospinal fluid is involved in the transport of thyroxine and retinol
      binding protein:retinol complex (holo-RBP). TTR forms two T4 binding sites at the
      center of the dimer-dimer interface and contains holo-RBP binding sites on both
      faces of the tetramer. Dissociation of TTR tetramers followed by misfolding and
      misassembly results in amyloid fibril formation, the causative agent of four
      neurodegenerative diseases. Misfolding of wild type TTR in humans over 60 years
      of age is linked to a sporadic amyloid disease called senile systemic
      amyloidosis. Single point mutations enhance the amyloidogenicity of TTR, causing
      familial amyloid cardiomyopathy, familial amyloid polyneuropathy, and central
      nervous system selective amyloidosis. To date, nearly 200 X-ray crystal
      structures of TTR and their complexes have been solved. They have provided
      potential insights into its structure-function relationships with molecular
      partners, and its interactions with small molecule ligands that inhibit tetramer
      destabilization and amyloid formation. This review will focus on the key findings
      of the structural studies of TTR that provided atomic level description of its
      architecture, the mechanistic role of structural components involved in its
      function and misfolding, and the progress and limitations towards the design of
      selective inhibitors for TTR amyloidoses.

PMID- 22471982
TI  - Transthyretin deposition in familial amyloidotic polyneuropathy.
AB  - The subject of the review is on hereditary transthyretin (TTR) amyloidosis which
      is a genetically transmitted disease that results from a mutation in the gene
      encoding the plasma TTR protein. TTR is a transport protein for thyroid hormones
      and vitamin A and is predominantly synthesised in the liver. Although originally
      regarded as a rare disease, it is now becoming clear that many kindreds exist
      worldwide. Current knowledge and hypotheses on the biology of TTR, mechanisms of
      TTR amyloid fibril formation, phenotypic consequences TTR amyloid deposition and
      pre-clinical models of the disease will be discussed.

PMID- 22471983
TI  - Methods to evaluate the inhibition of TTR fibrillogenesis induced by small
      ligands.
AB  - Transthyretin is an amyloidogenic protein associated with several amyloidosis,
      namely familial amyloidotic polyneuropathy, familial amyloidotic cardiomyopathy,
      and central nervous system selective amyloidosis, familial rare diseases caused
      by single point mutants, and senile systemic amyloidosis associated with wild
      type TTR. The current model for amyloid fibril formation involves initial
      dissociation of the native TTR tetramer into non-native monomers which associate
      into soluble oligomers and protofibrils that evolve to mature amyloid deposits. A
      number of efforts are addressed to identify small molecules targeting the
      formation, clearance, or assembly of toxic aggregates as a promising therapeutic
      strategy to treat amyloidosis. This review classifies and summarizes the
      different strategies and assays that have been developed in vitro, ex vivo, and
      in vivo as tools to screen libraries of compounds or to test compounds from
      rational design in the search of drug candidates for the treatment of TTR
      associated amyloidosis. Depending on the property they measure, the assays are
      classified as: a) in vitro assays that monitor protein aggregation and/or fibril
      formation, b) in vitro assays that monitor binding to native protein, c) ex vivo
      TTR plasma selectivity assays, d) in vitro assays for tetrameric TTR
      stabilization, e) cellular assays, and f) animal models to evaluate amyloidosis
      inhibitors.

PMID- 22471984
TI  - TTR fibril formation inhibitors: is there a SAR?
AB  - Transthyretin is a homotetrameric protein that carries thyroxine and retinol
      binding protein in plasma and is associated with a variety of amyloid diseases.
      One approach to the potential treatment of TTR amyloidosis is the stabilization
      of the native tetramer, over the dissociative transition state, through the
      binding of small molecules; this increases the kinetic barrier for tetramer
      dissociation and prevents protein misfolding. Several molecules discovered
      through focused screening, or created utilizing the structure-based design, were
      studied to identify the structural features that could make up for a good
      candidate drug. In this review, we examine several different chemical classes of
      TTR fibril formation inhibitors, highlighting the structural modifications that
      have led to an improvement or to a decrease of their potency and/or selectivity.

PMID- 22471985
TI  - Computational studies on transthyretin.
AB  - Among the 23 different fibril proteins described in human amyloidosis,
      transthyretin is associated with the most common hereditary form of the disease
      and its knowledge is corroborated through about 150 crystal structures in
      addition to thousands of small ligands tested as fibril formation inhibitors. In
      spite of the large amount of available data, the mechanism of transthyretin
      aggregation and its inhibition through binding with small ligands is not clear.
      In the last decade, many groups of researchers have attempted to apply
      computational procedures to simulate these phenomena, with the aim of
      understanding them in depth and in order to rationalize the design of new
      promising inhibitors. A summary of the main molecular dynamics, docking, and
      structure-activity relationship studies carried out on transthyretin are reviewed
      here, and the most successful results and new trends are described in detail.

PMID- 22471986
TI  - Investigation of the pH-dependent electron transfer mechanism of ascomycetous
      class II cellobiose dehydrogenases on electrodes.
AB  - Cellobiose dehydrogenase (CDH) is capable of direct electron transfer (DET) on
      various carbon and thiol-modified gold electrodes. As a result, these systems
      have been utilized as biocatalyst in biosensors and biofuel cell anodes. Class I
      CDHs, from basidiomycetous fungi, are highly specific to cellulose or lactose,
      and DET is only observed at pH values below 5.5. To extend the applicability of
      CDH-based electrodes, the catalytic properties and the behavior on electrode
      surfaces of ascomycetous class II CDHs from Chaetomium attrobrunneum, Corynascus
      thermophilus, Dichomera saubinetii, Hypoxylon haematostroma, Neurospora crassa,
      and Stachybotrys bisbyi were investigated. We found that class II CDHs have
      diverse properties but generally show a lower substrate specificity than class I
      CDHs by converting also glucose and maltose. Intramolecular electron transfer
      (IET) and DET at neutral and alkaline pH were observed and elucidated by steady
      state kinetics, pre-steady-state kinetics, and electrochemical measurements. The
      CDHs ability to interact with the electron acceptor cytochrome c and to
      communicate with electrode surfaces through DET at various pH conditions was used
      to classify the investigated enzymes. In combination with stopped-flow
      measurements, a model for the kinetics of the pH-dependent IET is developed. The
      efficient glucose turnover at neutral/alkaline pH makes some of these new CDHs
      potential candidates for glucose biosensors and biofuel cell anodes. 

PMID- 22471987
TI  - Sticker charts: a method for improving adherence to treatment of chronic diseases
      in children.
AB  - Poor adherence is a common problem and may be an underlying cause of poor
      clinical outcomes. In pediatric populations, positive reinforcement techniques
      such as sticker charts may increase motivation to adhere to treatment regimens.
      To review the use of sticker charts to improve adherence in children with chronic
      disease, Medline and PsycINFO searches were conducted using the key words
      "positive reinforcement OR behavior therapy" and "adherence OR patient
      compliance" and "child." Randomized controlled retrospective cohort or single
      subject-design studies were selected. Studies reporting adherence to the medical
      treatment of chronic disease in children using positive reinforcement techniques
      were included in the analysis. The systematic search was supplemented by
      identifying additional studies identified through the reference lists and authors
      of the initial articles found. Positive reinforcement techniques such as sticker
      charts increase adherence to medical treatment regimens. In several studies, this
      effect was maintained for months after the initial intervention. Better adherence
      correlated with better clinical outcomes in some, but not all, studies. Few
      studies examining the use of sticker charts were identified. Although single
      subject-design studies are useful in establishing the effect of a behavioral
      intervention, larger randomized controlled trials would help determine the
      precise efficacy of sticker chart interventions. Adherence to medical treatments
      in children can be increased using sticker charts or other positive reinforcement
      techniques. This may be an effective means to encourage children with atopic
      dermatitis to apply their medications and improve clinical outcomes.

PMID- 22471988
TI  - Differentiating between genuine damage and falsified damage to a garment
      following an alleged sexual assault.
AB  - An allegation of sexual assault was made in which a bra was torn off by the
      assailant causing extensive damage; however, it was observed that the hook and
      eye fastening was still intact. It was felt that it was not possible for a
      garment to receive such damage without damage to the hook and eye fastening, thus
      indicating that the complainant caused the damage to the bra herself to support a
      false allegation. Reconstruction experiments were conducted in which the
      conditions of the allegation were simulated utilizing a range of similar bras.
      Following the infliction of damage, the hook and eye fastenings were examined. In
      eight of nine experiments, the hook and eye fastening were intact, despite the
      application of enough force to cause separation of the bra cups in five of the
      experiments. This shows that bras may suffer extensive damage without damage to
      the hook and eye fastening.

PMID- 22471989
TI  - Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with
      chronic kidney disease.
AB  - BACKGROUND: The prevalence of cardiovascular disease (CVD) and inflammation is
      high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an
      adipocytokine that may have significant anti-inflammatory and anti
      atherosclerotic effects. Low adiponectin levels have previously been found in
      patients with high risk for CVD. METHODS: On seventy eight advanced CKD (stages 4
      and 5) pediatric patients undergoing maintenance hemodialysis( MHD) or
      conservative treatment (CT) the following parameters were studied: body mass
      index, left ventricular mass index(LVMI), serum adiponectin , cholesterol, HDL
      cholesterol, high sensitivity C-reactive protein (hs CRP),interleukin 6(IL6) and
      single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene at positions 45, and
      276. Seventy age-and gender-matched healthy subjects served as control subjects.
      RESULTS: Markedly (P = 0.01) elevated plasma adiponectin levels were observed in
      CKD patients, especially CT patients, compared to control subjects. The wild type
      of ADIPOQ 45T > G (T) allele is the main gene for patients and controls. MHD and
      CT patients had significantly higher frequency of the TT genotypes of +276G > T
      gene (P = 0.04) compared with control subjects. A significant positive
      correlation was observed between plasma adiponectin and IL6 level, whereas
      negative correlations were found between adiponectin level, cholesterol, HDL
      cholesterol and hs CRP. In a stepwise backward multiple regression model only IL6
      (P = 0.001) was independently associated with plasma adiponectin levels. The
      adiponectin gene the 276 GT+TT genotypes were associated with a higher level of
      adiponectin . CONCLUSIONS: The present study demonstrated that ADPN is related to
      several metabolic and inflammatory CV risk factors in a manner consistent with
      the hypothesis that this protein might have a protective role against these
      factors. We observed an association between the +276G>T SNP in the adiponectin
      gene and CKD in children. Genetic variation of +276 gene seemed to have a
      positive impact on circulating adiponectin levels in CKD patients.

PMID- 22471990
TI  - Effects of swimming training on tissue glycogen content in experimental
      thyrotoxic rats.
AB  - Thyrotoxicosis, a condition in which there is an excessive amount of circulating
      thyroid hormones, leads to reduced glycogen content in different tissues. In this
      study we analyzed the effects of aerobic swimming training on liver, heart, and
      skeletal muscle glycogen content in experimentally induced thyrotoxicosis. Wistar
      male rats were divided into euthyroid sedentary (ES, n = 12), euthyroid trained
      (ET, n = 11), thyrotoxic sedentary (TS, n = 12), and thyrotoxic trained (TT, n =
      10) groups. Thyrotoxic groups received daily i.p. doses of T4 (sodium
      levothyroxine, 25 ug/100 g body mass) through the experimental period, and
      trained groups swam for 1 h at 80% of the aerobic-anaerobic transition intensity,
      5 days/week for 4 weeks. Heart and liver glycogen stores were ~30% lower in T4
      treated compared with nontreated groups, but were not changed by training status.
      On the other hand, glycogen content in mixed fiber type gastrocnemius of TT was
      1.5- to 2.3-fold greater than those in other groups, whereas no significant
      differences were found for the slow soleus muscle. Increased gastrocnemius but
      not soleus, liver, or heart glycogen indicates that in mild long-term
      thyrotoxicosis chronic swimming affects glycogen stores in a tissue-specific
      manner.

PMID- 22471991
TI  - Can increases in capillarization explain the early adaptations in metabolic
      regulation in human muscle to short-term training?
AB  - To investigate the hypothesis that increases in fibre capillary density would
      precede increases in oxidative potential following training onset, tissue was
      extracted from the vastus lateralis prior to (0 days) and following 3 and 6
      consecutive days of submaximal cycle exercise (2 h.day(-1)). Participants were
      untrained males (age = 21.4 +/- 0.58 years; peak oxygen consumption = 46.2 +/-
      1.6 mL.kg(-1).min(-1); mean +/- standard error (SE)). Tissue was assessed for
      succinic dehydrogenase activity (SDH) by microphotometry and indices of
      capillarization based on histochemically assessed area and capillary counts (CC)
      in specific fibre types. Three days of training (n = 13) resulted in a
      generalized decrease (p < 0.05) in fibre area (-14.2% +/- 3.0%; mean +/- SE) and
      increase (p < 0.05) in CC/Area (20.4% +/- 2.7%) and no change in either CC or SDH
      activity. Following 6 days of treatment (n = 6), increases (p < 0.05) in CC
      (18.2% +/- 4.2%), CC/Area (28.9% +/- 3.2%), and SDH activity (22.9% +/- 6.0%)
      occurred that was not specific to major fibre type. No changes in either fibre
      area or fibre-type distribution were observed with additional training. We
      conclude that increases in angiogenic-based capillary density and oxidative
      potential occur coincidentally following training onset, while increases in
      capillary density, mediated by reductions in fibre area, represent an initial
      isolated response, the significance of which may be linked to the metabolic
      alterations that also result.

PMID- 22471992
TI  - Classical electrical and hydraulic Windkessel models validate physiological
      calculations of Windkessel (reservoir) pressure.
AB  - Our "reservoir-wave approach" to arterial hemodynamics holds that measured
      arterial pressure should be considered to be the sum of a volume-related pressure
      (i.e., reservoir pressure, P(reservoir)) and a wave-related pressure (P(excess)).
      Because some have questioned whether P(reservoir) (and, by extension, P(excess))
      is a real component of measured physiological pressure, it was important to
      demonstrate that P(reservoir) is implicit in Westerhof's classical electrical and
      hydraulic models of the 3-element Windkessel. To test the validity of our
      P(reservoir) determinations, we studied a freeware simulation of the electrical
      model and a benchtop recreation of the hydraulic model, respectively, measuring
      the voltage and the pressure distal to the proximal resistance. These
      measurements were then compared with P(reservoir), as calculated from
      physiological data. Thus, the first objective of this study was to demonstrate
      that respective voltage and pressure changes could be measured that were similar
      to calculated physiological values of P(reservoir). The second objective was to
      confirm previous predictions with respect to the specific effects of
      systematically altering proximal resistance, distal resistance, and capacitance.
      The results of this study validate P(reservoir) and, thus, the reservoir-wave
      approach.

PMID- 22471993
TI  - Muscle cellular properties in the ice hockey player: a model for investigating
      overtraining?
AB  - In this study, we hypothesized that athletes involved in 5-6 months of sprint
      type training would display higher levels of proteins and processes involved in
      muscle energy supply and utilization. Tissue was sampled from the vastus
      lateralis of 13 elite ice hockey players (peak oxygen consumption = 51.8 +/- 1.3
      mL.kg(-1).min(-1); mean +/- standard error) at the end of a season (POST) and
      compared with samples from 8 controls (peak oxygen consumption = 45.5 +/- 1.4
      mL.kg(-1).min(-1)) (CON). Compared with CON, higher activities were observed in
      POST (p < 0.05) only for succinic dehydrogenase (3.32 +/- 0.16 mol.(mg protein)(
      1).min(-1) vs. 4.10 +/- 0.11 mol.(mg protein)(-1).min(-1)) and hexokinase (0.73
      +/- 0.05 mol.(mg protein)(-1).min(-1) vs. 0.90 +/- 0.05mol.(mg protein)(-1).min(
      1)) but not for phosphorylase, phosphofructokinase, and creatine phosphokinase.
      No differences were found in Na(+),K(+)-ATPase concentration (beta(max): 262 +/-
      36 pmol.(g wet weight)(-1) vs. 275 +/- 27 pmol.(g wet weight)(-1)) and the
      maximal activity of the sarcoplasmic reticulum Ca(2+)-ATPase (98.1 +/- 6.1
      umol.(g protein)(-1).min(-1) vs. 102 +/- 3.3 umol.(g protein)(-1).min(-1)). Cross
      sectional area was lower (p < 0.05) in POST but only for the type IIA fibres
      (6312 +/- 684 MUm(2) vs. 5512 +/- 335 MUm(2)), while the number of capillary
      counts per fibre and the capillary to fibre area ratio were generally higher (p <
      0.05). These findings suggest that elite trained ice hockey players display
      elevations only in support of glucose-based aerobic metabolism that occur in the
      absence of alterations in excitation-contraction processes.

PMID- 22471994
TI  - The clinical significance of tumor infiltrating lymphoctyes in breast cancer:
      does subtype matter?
AB  - Tumor infiltrating lymphocytes (TILs) are commonly detected in breast tumors but
      their bearing on disease outcome is uncertain. The importance of TILs appears to
      be subtype-specific and varies depending on the histologic characteristics of the
      tumor. As our understanding of tumorigenesis is increasing the relevance of
      immunobiology will become apparent.

PMID- 22471995
TI  - Explaining failure through success: a critical analysis of reduction in road and
      stroke deaths as an explanation for Australia's low deceased organ donation
      rates.
AB  - BACKGROUND/AIM: During the past two decades, Australian federal and state
      governments have funded many initiatives to bolster organ donation. Despite large
      investments of time, effort and money, Australia's deceased donation rate is in
      the bottom half of the Organisation for Economic Co-operation and Development
      countries and has only marginally increased from 11.9 donors per million people
      (pmp) in 1990 to 14.9 donors pmp in 2011. An often-cited explanation for this
      situation is that Australia's success in increasing levels of public health and
      safety through reduced traffic and stroke fatalities has reduced its number of
      potential deceased organ donors. We refer to this as the 'Failure Because of
      Success' hypothesis. Although commonly accepted, this hypothesis is largely
      untested. METHODS: By analysing data from international donation and
      transplantation organisations and international public health and safety
      organisations, we compared historical deceased organ donation rates with traffic
      and stroke fatality rates in Australia and the seven countries with the world's
      highest deceased organ donation rates (Spain, Portugal, France, USA, Belgium,
      Austria and Italy). RESULTS: Traffic fatality rates across all countries in the
      study have fallen dramatically during the time period, with Spain having the
      lowest traffic fatality rates. Stroke fatality rates demonstrate similar
      reductions, with France showing the lowest cerebral vascular accident mortality
      rates. CONCLUSION: When compared with countries with the world's highest deceased
      donation rates, Australia's improvements to public health and safety through
      reductions in traffic and stroke fatalities were neither unique nor exemplary and
      do not provide an adequate explanation for its low organ donor rates.

PMID- 22471996
TI  - The impact of the G-quadruplex conformation in the development of novel
      therapeutic and diagnostic agents.

PMID- 22471997
TI  - Selection of mosquito life-histories: a hidden weapon against malaria?
AB  - BACKGROUND: There has recently been a substantial decline in malaria incidence in
      much of Africa. While the decline can clearly be linked to increasing coverage of
      mosquito vector control interventions and effective drug treatment in most
      settings, the ubiquity of reduction raises the possibility that additional
      ecological and associated evolutionary changes may be reinforcing the
      effectiveness of current vector control strategies in previously unanticipated
      ways. PRESENTATION OF HYPOTHESIS: Here it is hypothesized that the increasing
      coverage of insecticide-treated bed nets and other vector control methods may be
      driving selection for a shift in mosquito life history that reduces their ability
      to transmit malaria parasites. Specifically it is hypothesized that by
      substantially increasing the extrinsic rate of mortality experienced in vector
      populations, these interventions are creating a fitness incentive for mosquitoes
      to re-allocate their resources towards greater short-term reproduction at the
      expense of longer-term survival. As malaria transmission is fundamentally
      dependent on mosquito survival, a life history shift in this direction would
      greatly benefit control. TESTING THE HYPOTHESIS: At present, direct evaluation of
      this hypothesis within natural vector populations presents several logistical and
      methodological challenges. In the meantime, many insights can be gained from
      research previously conducted on wild Drosophila populations. Long-term selection
      experiments on these organisms suggest that increasing extrinsic mortality by a
      magnitude similar to that anticipated from the up-scaling of vector control
      measures generated an increase in their intrinsic mortality rate. Although this
      increase was small, a change of similar magnitude in Anopheles vector populations
      would be predicted to reduce malaria transmission by 80%. IMPLICATIONS OF
      HYPOTHESIS: The hypothesis presented here provides a reminder that evolutionary
      processes induced by interventions against disease vectors may not always act to
      neutralize intervention effectiveness. In the search for new intervention
      strategies, consideration should be given to both the potential disadvantages and
      advantages of evolutionary processes resulting from their implementation, and
      attempts made to exploit those with greatest potential to enhance control.

PMID- 22471998
TI  - Microglia differentiation using a culture system for the expansion of mice non
      adherent bone marrow stem cells.
AB  - INTRODUCTION: Studying primary adult microglia is hampered because of the
      difficult isolation procedure and the low cell yield. We therefore established a
      differentiation protocol using a culture system developed for the expansion of
      non-adherent bone marrow cells. METHODS: Non-adherent bone marrow derived stem
      cells (NA-BMC) are derived by selective adhesion ('preplating') and are non
      adhesive adult stem cells. We investigated the changes in bone marrow cell
      populations by this repeated selective adhesion and compared the potential of the
      derived cells to differentiate towards microglia. Cells were differentiated with
      astrocyte conditioned medium (ACM) and granulocyte-monocyte colony stimulating
      factor (GM-CSF). RESULTS: NA-BMC cultures show a steep raise in the fraction of
      stem cells during the cultivation time and the differentiation potential is of
      the same quality as established protocols. Around 70% of the cells are microglia
      defined as being positive for CD11b/CD45 and show phagocytosis activity and
      oxidative bursts. CONCLUSION: The non-adherent cell system has the advantage that
      is produces stem cell progenitors during expansion and provides good microglial
      differentiation.

PMID- 22471999
TI  - Relaxant effect induced by wogonin from Scutellaria baicalensis on rat isolated
      uterine smooth muscle.
AB  - CONTEXT: Wogonin is a flavone derivative isolated from Scutellaria baicalensis
      Georgi (Labiatae) root, which is a traditional Chinese drug used as an anti
      inflammatory and for management of dysmenorrhea. OBJECTIVE: The effect of wogonin
      on the uterus has not yet been examined. We investigated the relaxant effects of
      wogonin on contractile activity of isolated uterine strips of rats. MATERIALS AND
      METHODS: The effect of wogonin on spontaneous uterine contraction, and uterine
      contraction induced by agonists, K+-depolarization and oxytocin in Ca2+-free
      solution was observed. To clarify the type of potassium channel, we tested the
      effects of 4-aminopyridine, tetraethylammonium and glibenclamide. RESULTS:
      Wogonin reduced the contractile amplitude of uterine strip smooth muscle of rats
      in a dose-dependent manner. The concentration of wogonin for reducing the
      contraction amplitude by 50% (IC50) on spontaneous contractions was 60.5 MUM.
      Wogonin also inhibited the contraction induced by three agonists (oxytocin,
      prostaglandin F(2alpha) and acetylcholine). For the uterine strips pretreated
      with oxytocin in Ca2+-free solution or K+-depolarization, wogonin showed relaxant
      effect on the induced uterine contractions. In addition, whereas the inhibitive
      effect of wogonin on the contraction of uterine smooth muscle in rats could be
      partly blocked by 4-aminopyridine and tetraethylammonium, it was not influenced
      by glibenclamide. DISCUSSION AND CONCLUSION: Wogonin significantly inhibited the
      contraction of rat uterine smooth muscle probably through the inhibition of the
      inflow of extracellular calcium into cells via cell membrane, and intracellular
      release of calcium ions. In addition, the relaxant effect induced by wogonin
      might be due in part to the opening of voltage-dependent and large conductance
      Ca2+-activated K+ channels.

PMID- 22472000
TI  - Age-dependent morphology of NADPH diaphorase-positive amacrine cells in the mouse
      retina.
AB  - NADPH diaphorase-positive amacrine cells (NAC) were studied in retinal whole
      mount preparation of mice, ranging from 1 day to 30 months of age. Following a
      peak in number and size during early development at postnatal day 14, their
      number and distribution remained well preserved up to senescence. Functional
      considerations include immunological, vascular and neuro-modulating aspects.

PMID- 22472001
TI  - Uncovering middle managers' role in healthcare innovation implementation.
AB  - BACKGROUND: Middle managers have received little attention in extant health
      services research, yet they may have a key role in healthcare innovation
      implementation. The gap between evidence of effective care and practice may be
      attributed in part to poor healthcare innovation implementation. Investigating
      middle managers' role in healthcare innovation implementation may reveal an
      opportunity for improvement. In this paper, we present a theory of middle
      managers' role in healthcare innovation implementation to fill the gap in the
      literature and to stimulate research that empirically examines middle managers'
      influence on innovation implementation in healthcare organizations. DISCUSSION:
      Extant healthcare innovation implementation research has primarily focused on the
      roles of physicians and top managers. Largely overlooked is the role of middle
      managers. We suggest that middle managers influence healthcare innovation
      implementation by diffusing information, synthesizing information, mediating
      between strategy and day-to-day activities, and selling innovation
      implementation. SUMMARY: Teamwork designs have become popular in healthcare
      organizations. Because middle managers oversee these team initiatives, their
      potential to influence innovation implementation has grown. Future research
      should investigate middle managers' role in healthcare innovation implementation.
      Findings may aid top managers in leveraging middle managers' influence to improve
      the effectiveness of healthcare innovation implementation.

PMID- 22472002
TI  - Quarantine, isolation, and cohorting: from cholera to Klebsiella.
AB  - BACKGROUND: Isolation is defined as the separation of persons with communicable
      diseases from those who are healthy. This public health practice, along with
      quarantine, is used to limit the transmission of infectious diseases and provides
      the foundation of current-day cohorting. METHODS: Review of the pertinent English
      language literature. RESULTS: Mass isolation developed during the medieval Black
      Death outbreaks in order to protect ports from the transmission of epidemics. In
      the mid-1800s, infectious disease hospitals were opened. It now is clear that
      isolation and cohorting of patients and staff interrupts the transmission of
      disease. Over the next century, with the discovery of penicillin and vaccines
      against many infectious agents, the contagious disease hospitals began to close.
      Today, we find smaller outbreaks of microorganisms that have acquired substantial
      resistance to antimicrobial agents. In the resource-limited hospital, a dedicated
      area or region of a unit may suffice to separate affected from unaffected
      patients. CONCLUSION: Quarantine, or cohorting when patients are infected with
      the same pathogen, interrupts the spread of infections, just as the contagious
      disease hospitals did during the epidemics of the 18th and 19th centuries.

PMID- 22472003
TI  - Successful liver transplantation from donor with Plesiomonas shigelloides sepsis
      after freshwater drowning: case report and review of literature on gram-negative
      bacterial aspiration during drowning and utilization of organs from bacteremic
      donors.
AB  - BACKGROUND: Plesiomonas shigelloides is a freshwater, non-fermentative gram
      negative bacillus associated with diarrheal disease. Rare cases of invasive
      infection in human beings usually involve immunosuppressed individuals. METHODS:
      We report a patient who underwent successful liver transplantation (LT) using a
      graft from a 14-year-old boy who had drowned in a freshwater lake. PUBMED was
      searched for both reported drowning victims with sepsis and outcomes of LT using
      organs from infected donors. RESULTS: Our patient received prophylactic
      piperacillin-tazobactam, which was switched to cefepime one day after
      transplantation when gram-negative bacteria grew in blood cultures of the donor.
      The next day, the organism was identified as P. shigelloides resistant to third-
      and fourth-generation cephalosporins; ciprofloxacin was given for seven days, and
      surveillance cultures remained negative. After an uneventful course the patient
      was discharged on day 10 after LT without signs of infection and is alive with a
      well-functioning graft. Literature review revealed one case of P. shigelloides in
      a potential allograft, in which the organism was isolated from heart valves of a
      drowning victim; the organs were discarded. Reports of freshwater drowning show
      that bacteremia is universally found post-mortem. Isolated pathogens correspond
      to specimens from the drowning site, with Aeromonas spp. being the most common
      and many other microorganisms described anecdotally. Livers from infected donors
      have been used, in most cases with good results if the recipient and, when
      possible, donor were treated appropriately; however, cases of fatal pathogen
      transmission have been reported. CONCLUSION: This is the first reported case of a
      LT using a graft from a donor with P. shigelloides sepsis. Drowning victims
      should be considered potentially infected with rare pathogens and therefore
      represent extended-criteria donors.

PMID- 22472004
TI  - Redox regulation of SERCA2 is required for vascular endothelial growth factor
      induced signaling and endothelial cell migration.
AB  - AIMS: Vascular endothelial growth factor (VEGF) increases angiogenesis by
      stimulating endothelial cell (EC) migration. VEGF-induced nitric oxide ((*)NO)
      release from (*)NO synthase plays a critical role, but the proteins and signaling
      pathways that may be redox-regulated are poorly understood. The aim of this work
      was to define the role of (*)NO-mediated redox regulation of the
      sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) in VEGF-induced signaling and
      EC migration. RESULTS: VEGF-induced EC migration was prevented by the (*)NO
      synthase inhibitor, N (G)-nitro-L-arginine methyl ester (LNAME). Either VEGF or
      (*)NO stimulated endoplasmic reticulum (ER) (45)Ca(2+) uptake, a measure of SERCA
      activity, and knockdown of SERCA2 prevented VEGF-induced EC migration and
      (45)Ca(2+) uptake. S-glutathione adducts on SERCA2b, identified immunochemically,
      were increased by VEGF, and were prevented by LNAME or overexpression of
      glutaredoxin-1 (Glrx-1). Furthermore, VEGF failed to stimulate migration of ECs
      overexpressing Glrx-1. VEGF or (*)NO increased SERCA S-glutathiolation and
      stimulated migration of ECs in which wild-type (WT) SERCA2b was overexpressed
      with an adenovirus, but did neither in those overexpressing a C674S SERCA2b
      mutant, in which the reactive cysteine-674 was mutated to a serine. Increased EC
      Ca(2+) influx caused by VEGF or (*)NO was abrogated by overexpression of Glrx-1
      or the C674S SERCA2b mutant. ER store-emptying through the ryanodine receptor
      (RyR) and Ca(2+) entry through Orai1 were also required for VEGF- and (*)NO
      induced EC Ca(2+) influx. INNOVATION AND CONCLUSIONS: These results demonstrate
      that (*)NO-mediated activation of SERCA2b via S-glutathiolation of cysteine-674
      is required for VEGF-induced EC Ca(2+) influx and migration, and establish redox
      regulation of SERCA2b as a key component in angiogenic signaling.

PMID- 22472005
TI  - Type V aplasia cutis congenita: case report, review of the literature, and
      proposed treatment algorithm.
AB  - Aplasia cutis congenita (ACC) is the congenital absence of skin. There are a
      number of different classifications based on distribution and associated
      findings. Type V ACC is unique in that the lesions are typically symmetric and
      found primarily on the trunk but can also include the upper and lower
      extremities. Type V is associated with the loss of a monozygotic co-twin during
      the late first or early second trimester. Here we present an extensive case of
      type V ACC and a review of the literature, including a summary of treatment and
      outcomes. From the available literature, it appears that there is no benefit from
      early surgical intervention, and therefore we propose a treatment algorithm that
      starts with conservative management. 

PMID- 22472007
TI  - British adolescents' and young adults' understanding and reasoning about the
      religious and nonreligious rights of asylum-seeker youth.
AB  - This study examined British young people's understanding of the rights of asylum
      seeking young people. Two hundred sixty participants (11-24 years) were read
      vignettes involving asylum-seeking young people's religious and nonreligious self
      determination and nurturance rights. Religious rights were more likely to be
      endorsed than nonreligious rights. In general, younger participants were more
      likely than older participants to endorse the rights of asylum-seeking young
      people. Supporting a social cognitive domain approach, patterns of reasoning
      varied with the type of right and whether scenarios involved religious or
      nonreligious issues. Few developmental differences were found regarding
      participants' reasoning about asylum-seeking young people's religious or
      nonreligious rights. The findings are discussed with reference to available
      theory and research on young people's conceptions of rights.

PMID- 22472009
TI  - Socioeconomic factors and phthalate metabolite concentrations among United States
      women of reproductive age.
AB  - INTRODUCTION: Relatively little is known about the socioeconomic correlates of
      phthalate metabolite urine concentrations among the general population, exposures
      of increasing public health concern, particularly for women of reproductive age.
      METHODS: We pooled data from the 2001-2008 cycles of the National Health and
      Nutrition Examination Survey to examine the associations between phthalate
      metabolite concentrations (including the molar sum of four di-2-ethylhexyl
      phthalate (DEHP) metabolites, the molar sum of two dibutyl phthalate (DBP)
      metabolites, and metabolites of benzylbutyl phthalate (BzBP) and diethyl
      phthalate (DEP)) with socioeconomic indicators (including ethnicity, education,
      income, and food security status) among women 20 to 39 years age. We also derived
      a socioeconomic status summary measure using factor analysis and investigated its
      associations with metabolite concentrations. RESULTS: In fully adjusted models,
      the lowest quartile of overall socioeconomic status was associated with 1.83 (95%
      CI=1.54-2.17) times the concentrations of mono-benzyl phthalate (MBzP), and 0.72
      (95% CI=0.54-0.98) times the concentrations of (molar sum) DEHP metabolites
      compared with the highest quartile of overall socioeconomic status. This latter
      association was driven primarily by educational attainment. All Non-White
      ethnicities combined had 1.24 (95% CI=1.09-1.40) times the concentrations of
      (molar sum) DBP metabolites, 1.32 (95% CI=1.12-1.56) times the mono-ethyl
      phthalate (MEP) concentrations, and 0.82 (95% CI=0.71-0.96) the concentrations of
      MBzP of Non-Hispanic Whites. CONCLUSIONS: Biomarkers of phthalate exposure vary
      with socioeconomic factors in women of reproductive age in the United States.
      Given the public health concern surrounding phthalate exposure, more research is
      needed to elucidate the reasons for these differences.

PMID- 22472010
TI  - Interferometer-based structured-illumination microscopy utilizing complementary
      phase relationship through constructive and destructive image detection by two
      cameras.
AB  - In an interferometer-based fluorescence microscope, a beam splitter is often used
      to combine two emission wavefronts interferometrically. There are two
      perpendicular paths along which the interference fringes can propagate and
      normally only one is used for imaging. However, the other path also contains
      useful information. Here we introduced a second camera to our interferometer
      based three-dimensional structured-illumination microscope (I(5)S) to capture the
      fringes along the normally unused path, which are out of phase by pi relative to
      the fringes along the other path. Based on this complementary phase relationship
      and the well-defined phase interrelationships among the I(5)S data components, we
      can deduce and then computationally eliminate the path length errors within the
      interferometer loop using the simultaneously recorded fringes along the two
      imaging paths. This self-correction capability can greatly relax the requirement
      for eliminating the path length differences before and maintaining that status
      during each imaging session, which are practically challenging tasks.
      Experimental data is shown to support the theory.

PMID- 22472011
TI  - Improving quality of breast cancer surgery through development of a national
      breast cancer surgical outcomes (BRCASO) research database.
AB  - BACKGROUND: Common measures of surgical quality are 30-day morbidity and
      mortality, which poorly describe breast cancer surgical quality with extremely
      low morbidity and mortality rates. Several national quality programs have
      collected additional surgical quality measures; however, program participation is
      voluntary and results may not be generalizable to all surgeons. We developed the
      Breast Cancer Surgical Outcomes (BRCASO) database to capture meaningful breast
      cancer surgical quality measures among a non-voluntary sample, and study
      variation in these measures across providers, facilities, and health plans. This
      paper describes our study protocol, data collection methods, and summarizes the
      strengths and limitations of these data. METHODS: We included 4524 women >=18
      years diagnosed with breast cancer between 2003-2008. All women with initial
      breast cancer surgery performed by a surgeon employed at the University of
      Vermont or three Cancer Research Network (CRN) health plans were eligible for
      inclusion. From the CRN institutions, we collected electronic administrative data
      including tumor registry information, Current Procedure Terminology codes for
      breast cancer surgeries, surgeons, surgical facilities, and patient demographics.
      We supplemented electronic data with medical record abstraction to collect
      additional pathology and surgery detail. All data were manually abstracted at the
      University of Vermont. RESULTS: The CRN institutions pre-filled 30% (22 out of
      72) of elements using electronic data. The remaining elements, including detailed
      pathology margin status and breast and lymph node surgeries, required chart
      abstraction. The mean age was 61 years (range 20-98 years); 70% of women were
      diagnosed with invasive ductal carcinoma, 20% with ductal carcinoma in situ, and
      10% with invasive lobular carcinoma. CONCLUSIONS: The BRCASO database is one of
      the largest, multi-site research resources of meaningful breast cancer surgical
      quality data in the United States. Assembling data from electronic administrative
      databases and manual chart review balanced efficiency with high-quality, unbiased
      data collection. Using the BRCASO database, we will evaluate surgical quality
      measures including mastectomy rates, positive margin rates, and partial
      mastectomy re-excision rates among a diverse, non-voluntary population of
      patients, providers, and facilities.

PMID- 22472012
TI  - A community-based participatory approach and engagement process creates
      culturally appropriate and community informed pandemic plans after the 2009 H1N1
      influenza pandemic: remote and isolated First Nations communities of sub-arctic
      Ontario, Canada.
AB  - BACKGROUND: Public health emergencies have the potential to disproportionately
      impact disadvantaged populations due to pre-established social and economic
      inequalities. Internationally, prior to the 2009 H1N1 influenza pandemic,
      existing pandemic plans were created with limited public consultation; therefore,
      the unique needs and characteristics of some First Nations communities may not be
      ethically and adequately addressed. Engaging the public in pandemic planning can
      provide vital information regarding local values and beliefs that may ultimately
      lead to increased acceptability, feasibility, and implementation of pandemic
      plans. Thus, the objective of the present study was to elicit and address First
      Nations community members' suggested modifications to their community-level
      pandemic plans after the 2009 H1N1 influenza pandemic. METHODS: The study area
      included three remote and isolated First Nations communities located in sub
      arctic Ontario, Canada. A community-based participatory approach and community
      engagement process (i.e., semi-directed interviews (n = 13), unstructured
      interviews (n = 4), and meetings (n = 27)) were employed. Participants were
      purposively sampled and represented various community stakeholders (e.g., local
      government, health care, clergy, education, etc.) involved in the community's
      pandemic response. Collected data were manually transcribed and coded using
      deductive and inductive thematic analysis. The data subsequently informed the
      modification of the community-level pandemic plans. RESULTS: The primary
      modifications incorporated in the community-level pandemic plans involved adding
      community-specific detail. For example, 'supplies' emerged as an additional
      category of pandemic preparedness and response, since including details about
      supplies and resources was important due to the geographical remoteness of the
      study communities. Furthermore, it was important to add details of how, when,
      where, and who was responsible for implementing recommendations outlined in the
      pandemic plans. Additionally, the roles and responsibilities of the involved
      organizations were further clarified. CONCLUSIONS: Our results illustrate the
      importance of engaging the public, especially First Nations, in pandemic planning
      to address local perspectives. The community engagement process used was
      successful in incorporating community-based input to create up-to-date and
      culturally-appropriate community-level pandemic plans. Since these pandemic plans
      are dynamic in nature, we recommend that the plans are continuously updated to
      address the communities' evolving needs. It is hoped that these modified plans
      will lead to an improved pandemic response capacity and health outcomes, during
      the next public health emergency, for these remote and isolated First Nations
      communities. Furthermore, the suggested modifications presented in this paper may
      help inform updates to the community-level pandemic plans of other similar
      communities.

PMID- 22472013
TI  - A histopathologic study of fatal paediatric cerebral malaria caused by mixed
      Plasmodium falciparum/Plasmodium vivax infections.
AB  - Microvascular sequestration of Plasmodium falciparum underlies cerebral malaria.
      Despite suggestive ex vivo evidence, this phenomenon has not been convincingly
      demonstrated in coma complicating Plasmodium vivax malaria. Severely-ill Papua
      New Guinean children with mixed P. falciparum/P. vivax infections are more likely
      to develop cerebral malaria and die than those with P. falciparum alone, possibly
      reflecting P. vivax sequestration. Nested PCR was performed on post mortem brain
      tissue from three such children dying from cerebral malaria due to mixed-species
      infections. No P. vivax DNA was detected. These findings do not support the
      hypothesis that P. vivax sequestration occurs in human brain.

PMID- 22472014
TI  - Lamb waves in phononic crystal slabs: truncated plane parallels to the axis of
      periodicity.
AB  - A theoretical study is presented on the propagation properties of Lamb wave modes
      in phononic crystal slabs consisting of a row or more of parallel square
      cylinders placed periodically in the host material. The surfaces of the slabs are
      parallel to the axis of periodicity. The dispersion curves of Lamb wave modes are
      calculated based on the supercell method. The finite element method is employed
      to calculate the band structures and the transmission power spectra, which are in
      good agreement with the results by the supercell method. We also have found that
      the dispersion curves of Lamb waves are strongly dependent on the crystal
      termination, which is the position of the cut plane through the square cylinders.
      There exist complete or incomplete (truncated) layers of square cylinders with
      the change of the crystal termination. The influence of the crystal termination
      on the band gaps of Lamb wave modes is analyzed by numerical simulations. The
      variation of the crystal termination leads to obvious changes in the dispersion
      curves of the Lamb waves and the widths of the band gaps.

PMID- 22472015
TI  - Using ultrasound CBE imaging without echo shift compensation for temperature
      estimation.
AB  - Clinical trials have demonstrated that hyperthermia improves cancer treatments.
      Previous studies developed ultrasound temperature imaging methods, based on the
      changes in backscattered energy (CBE), to monitor temperature variations during
      hyperthermia. Echo shift, induced by increasing temperature, contaminates the CBE
      image, and its tracking and compensation should normally ensure that estimations
      of CBE at each pixel are correct. To obtain a simplified algorithm that would
      allow real-time computation of CBE images, this study evaluated the usefulness of
      CBE imaging without echo shift compensation in detecting distributions in
      temperature. Experiments on phantoms, using different scatterer concentrations,
      and porcine livers were conducted to acquire raw backscattered data at
      temperatures ranging from 37 degrees C to 45 degrees C. Tissue samples of pork
      tenderloin were ablated in vitro by microwave irradiation to evaluate the
      feasibility of using the CBE image without compensation to monitor tissue
      ablation. CBE image construction was based on a ratio map obtained from the
      envelope image divided by the reference envelope image at 37 degrees C. The
      experimental results demonstrated that the CBE image obtained without echo shift
      compensation has the ability to estimate temperature variations induced during
      uniform heating or tissue ablation. The magnitude of the CBE as a function of
      temperature obtained without compensation is stronger than that with
      compensation, implying that the CBE image without compensation has a better
      sensitivity to detect temperature. These findings suggest that echo shift
      tracking and compensation may be unnecessary in practice, thus simplifying the
      algorithm required to implement real-time CBE imaging.

PMID- 22472016
TI  - Allele discovery of ten candidate drought-response genes in Austrian oak using a
      systematically informatics approach based on 454 amplicon sequencing.
AB  - BACKGROUND: Rise of temperatures and shortening of available water as result of
      predicted climate change will impose significant pressure on long-lived forest
      tree species. Discovering allelic variation present in drought related genes of
      two Austrian oak species can be the key to understand mechanisms of natural
      selection and provide forestry with key tools to cope with future challenges.
      RESULTS: In the present study we have used Roche 454 sequencing and developed a
      bioinformatic pipeline to process multiplexed tagged amplicons in order to
      identify single nucleotide polymorphisms and allelic sequences of ten candidate
      genes related to drought/osmotic stress from sessile oak (Quercus robur) and
      sessile oak (Q. petraea) individuals. Out of these, eight genes of 336 oak
      individuals growing in Austria have been detected with a total number of 158
      polymorphic sites. Allele numbers ranged from ten to 52 with observed
      heterozygosity ranging from 0.115 to 0.640. All loci deviated from Hardy-Weinberg
      equilibrium and linkage disequilibrium was found among six combinations of loci.
      CONCLUSIONS: We have characterized 183 alleles of drought related genes from oak
      species and detected first evidences of natural selection. Beside the potential
      for marker development, we have created an expandable bioinformatic pipeline for
      the analysis of next generation sequencing data.

PMID- 22472017
TI  - Pretreatment with Bacopa monnieri extract offsets 3-nitropropionic acid induced
      mitochondrial oxidative stress and dysfunctions in the striatum of prepubertal
      mouse brain.
AB  - The present investigation was designed to determine the efficacy of Bacopa
      monnieri (Brahmi; BM) to offset 3-nitropropionic acid (3-NPA) induced oxidative
      stress and mitochondrial dysfunction in dopaminergic (N27) cells and prepubertal
      mouse brain. Pretreatment of N27 cells with BM ethanolic extract (BME)
      significantly attenuated 3-NPA-induced cytotoxicity. Further, we determined the
      degree of oxidative stress induction, redox status, enzymic antioxidants, and
      protein oxidation in the striatal mitochondria of mice given BME prophylaxis
      followed by 3-NPA challenge. While 3-NPA-induced marked oxidative stress in the
      mitochondria of the striatum, BME prophylaxis markedly prevented 3-NPA-induced
      oxidative dysfunctions and depletion of reduced glutathione and thiol levels. The
      activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase,
      glutathione reductase, thioredoxin reductase), Na(+),K(+)-ATPase, and citric acid
      cycle enzymes in the striatum discernible among 3-NPA mice were significantly
      restored with BME prophylaxis. Interestingly, BME offered protection against 3
      NPA-induced mitochondrial dysfunctions as evidenced by the restoration of the
      activities of ETC enzymes (NADH:ubiquinone oxidoreductase, NADH:cytochrome c
      reductase, succinate-ubiquinone oxidoreductase, and cytochrome c oxidase) and
      mitochondrial viability. We hypothesize that the neuroprotective effects of BME
      may be wholly or in part related to its propensity to scavenge free radicals,
      maintain redox status, and upregulate antioxidant machinery in striatal
      mitochondria.

PMID- 22472019
TI  - Traditional gender roles, forced sex and HIV in Zimbabwean marriages.
AB  - Little is known on how forced sex contributes to the sexual transmission of HIV
      in marriage. This paper describes traditional gender norms surrounding forced sex
      in Zimbabwean marriage. Data were collected from 4 focus group discussions and 36
      in-depth interviews with married women and men in Harare. Results indicate that
      hegemonic masculinity characterised by a perceived entitlement to sex, male
      dominance and being a provider contributed to forced sex in marriage. A
      femininity characterised by a tolerance of marital rape, the desire to please the
      husband and submission contributed to women experiencing forced sex. An
      alternative femininity characterised by sexual pleasure-seeking contributed to
      women forcing their spouses to have sex. Future HIV interventions must go beyond
      narrowly advocating for safer sex within marriage and instead address practices
      that increase risk as well as promote positive marital relationship needs such as
      mutual respect, love and friendship.

PMID- 22472020
TI  - School screening for scoliosis: can surface topography replace examination with
      scoliometer?
AB  - BACKGROUND: Clinical examination with the use of scoliometer is a basic method
      for scoliosis detection in school screening programs. Surface topography (ST)
      enables three-dimensional back assessment, however it has not been adopted for
      the purpose of scoliosis screening yet. The purpose of this study was to assess
      the usefulness of ST for scoliosis screening. METHODS: 996 girls aged 9 to 13
      years were examined, with both scoliometer and surface topography. The Surface
      Trunk Rotation (STR) was introduced and defined as a parameter allowing
      comparison with scoliometer Angle of Trunk Rotation taken as reference. RESULTS:
      Intra-observer error for STR parameter was 1.9 degrees , inter-observer error was
      0.8 degrees . Sensitivity and specificity of ST were not satisfactory, the
      screening cut-off value of the surface topography parameter could not be
      established. CONCLUSIONS: The study did not reveal advantage of ST as a scoliosis
      screening method in comparison to clinical examination with the use of the
      scoliometer.

PMID- 22472021
TI  - Factors influencing career decisions in internal medicine.
AB  - BACKGROUND: Numerous factors influence career decisions for internal medicine
      trainees and Fellows. There is a perception that a greater emphasis is placed on
      work-family balance by younger physicians. AIMS: To determine the characteristics
      of the modern internal medicine workforce and ascertain whether job flexibility
      is important to career decision-making. We hypothesised that factors which
      reflect flexibility would be highly influential in decision-making, especially
      for women and those with young children. METHODS: A questionnaire was mailed to
      250 New Zealand internal medicine trainees and Fellows. It focused on factors,
      including job flexibility, interest and collegial support, and included
      demographic details which were primarily aimed at ascertaining family
      responsibilities. RESULTS: Response rate was 54%. The majority of female
      physicians are the main person responsible for their children (62%), and the
      majority of their partners work full-time (80%). This contrasts with male
      physicians, of whom only 4% are the main person responsible for their children.
      Flexibility was found to be more influential in women, those with young children,
      trainees and those working in outpatient-based subspecialties. However, contrary
      to our original hypothesis, flexibility was not reported to be highly influential
      in any group, with career choice being most influenced by interest and enjoyment,
      intellectual challenge and variety within the job. CONCLUSION: It is hoped that
      results will inform employers and those involved with training to enable them to
      better cater for the needs of the workforce and also encourage trainees to
      consider future family commitments when making career decisions.

PMID- 22472022
TI  - A panel of oxidative stress assays does not provide supplementary diagnostic
      information in Behcet's disease patients.
AB  - BACKGROUND: Recent findings suggest a role of oxidative stress in the
      pathogenesis of Behcet's disease (BD), but the utility of oxidative stress
      associated assays in offering diagnostic information or in the monitoring of
      disease activity is largely unassessed. OBJECTIVE AND METHODS: We aimed to
      measure oxidative and inflammatory markers, along with the markers of reactive
      nitrogen species, S-nitrosothiols and 3-nitrotyrosine, in BD patients (n = 100)
      and healthy volunteers (n = 50). These markers were evaluated in regard to their
      role in the pathogenesis of BD as well as their relation to clinical
      presentation, disease activity and duration. RESULTS: Median values for
      erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, and IL
      18 levels, as well as myeloperoxidase (MPO) activity, were statistically higher
      in the patient group compared to controls. Some inflammation markers (ESR,
      neutrophil and leukocyte counts) were statistically higher (p < 0.05) in the
      active period. In contrast, oxidative stress-associated measures (erythrocyte
      lipid peroxidation, antioxidant enzymes and measures of serum antioxidant
      capacity), revealed no statistically significant differences between the median
      values in BD patients versus healthy control subjects (p > 0.05 in all
      statistical comparisons), nor was there any difference in median levels of these
      oxidative stress markers in active disease versus disease remission. S
      nitrosothiols and 3-nitrotyrosine were undetectable in BD plasma. CONCLUSIONS:
      The application of oxidative stress-associated measures to BD blood samples
      offered no supplemental diagnostic or disease activity information to that
      provided by standard laboratory measures of inflammation. S-nitrosothiols and 3
      nitrotyrosine appeared not to be markers for active BD; thus the search for
      biochemical markers that will indicate the active period should be continued with
      larger studies.

PMID- 22472023
TI  - In vitro antileishmanial, antiplasmodial and cytotoxic activities of a new
      ventiloquinone and five known triterpenes from Parinari excelsa.
AB  - CONTEXT: Parinari excelsa Sabine (Chrysobalanaceae) is an indigenous tree from
      West and Eastern Africa. This tree is used in Ivory Coast as an antimalaria
      remedy. OBJECTIVE: The in vitro antiplasmodial and antileishmanial activities of
      the stem bark, the leaf and the major compounds from the stem bark were
      investigated. MATERIALS AND METHODS: The leaves and stem bark from P. excelsa
      were separately collected, air-dried and powdered. Two extracts (methylene
      chloride and methanol) were realized for both powders. Every extract was tested
      for its antiplasmodial and antileishmanial activities. Only the stem bark crude
      extracts were fractionated by column chromatography and their major components
      were analyzed by NMR, HRESIMS and IR methods. The compounds were tested for their
      antiplasmodial and antileishmanial activities. RESULTS: The comparison of the
      IC(50) values of the crude extracts were in this order: 3.41 (IC(50) of PeBMc)
      <4.10 (IC(50) of PeBMc) <4.42 (IC(50) of PeLMe) against P. falciparum and 5.19
      (IC(50) of PeBMc) <12.32 (IC(50) of PeBMe) <19.33 (IC(50) of PeLMc) <32.37
      (IC(50) of PeLMe) against L. donovani. The stem bark crude extracts were the most
      active against both parasites. Their fractionation leaded to a new
      ventiloquinone, five triterpenes and one chlorogenic acid. All these compounds
      were isolated for the first time from P. excelsa. High activities were observed
      with (3beta)-3-hydroxyolean-12-en-28-oic acid (IC(50) = 8.2 uM) and 3beta
      hydroxyolean-5,12-dien-28-oic acid (IC(50) = 7.7 uM) against L. donovani. With
      the antiplasmodial activity, the best activity was observed with 16beta
      hydroxylupane-1,20(29)-dien-3-one (IC(50) = 28.3 uM). DISCUSSION AND CONCLUSION:
      These findings demonstrated that the constituents of P. excelsa stem bark have in
      vitro antiplasmodial and antileishmanial activities.

PMID- 22472024
TI  - The tachykinergic system as avenues for drug intervention.
AB  - This review discusses a family of receptors that interact with a family of small
      peptides that belong to the tachykinin family. The three subtypes of tachykinin
      receptors follow the following suggested nomenclature: NK1, NK2 and NK3. These
      receptors belong to the 7-transmembrane, G-protein coupled family. The NK
      receptor family has been implicated in a wide range of disorders, cancers,
      inflammation and neural-related diseases. The tachykinin NK receptors and their
      ligands have been implicated in solid and hematological tumors. Antagonists to NK
      receptors have been synthesized and some have been tested in preclinical and
      Phase II clinical studies. However, in order to be effective for treatment, it is
      imperative to understand the biology of NK receptor family as well as related
      molecules. One such molecule is HGFIN, also referred as nmb and osteoactivin.
      HGFIN is particularly relevant since it has been shown to interact with the high
      affinity ligand of NK1, substance P. This report discusses promising applications
      for targeting the NK receptors. The discussion proposes potential mechanisms that
      could occur when substance P interacts with HGFIN as well as the role of HGFIN
      when antagonists are used to block the NK receptors. This review is relevant for
      central and peripheral nervous system drug development and cancer targets and
      also discusses the indications for current patents.

PMID- 22472025
TI  - Nutraceuticals in psychiatric practice.
AB  - Nutraceuticals can be defined as food components or active principles present in
      aliments which have positive effects for health and quality of life, including
      preventing or treating disorders. Herbal and "natural" food supplements are
      increasingly used to treat different psychiatric disorders, often as "self
      prescribed" therapies. With factors such as chronic illness, poor health,
      emotional distress, and quality of life influencing the desire for complementary
      medicine, patients with comorbid medical and psychiatric problems seem likely to
      turn to this approach. We reviewed the most commonly used herbal and dietary
      supplements for which a certain efficacy on psychiatric symptoms or disorders has
      been claimed, checking current Pubmed-indexed literature (the most important
      being St. John's wort, Omega-3 fatty acids, valerian, Kava, Ginkgo, folate, B
      vitamins, S-Adenosylmethionine, inositol, alfa-lactoalbumin and passionflower).
      There is evidence of efficacy for some of these herbs an supplements, proved also
      by Cochrane's meta-analysis. However many different areas (including efficacy,
      tolerability, optimal dosing, adequate shelf life, drug and non-pharmacological
      interactions) need to be thoroughly studied; moreover political decisions need to
      be scientifically guided in order to best serve psychiatric patients' interests
      and to prevent using of expensive and sometimes un-useful therapies. This implies
      that a scientific strategy is needed to rule out any third-part economical
      interest which could in any way influence therapeutic choices. The article
      presents some promising patents on nutraceuticals in psychiatric practice.

PMID- 22472026
TI  - Clinical experience with infliximab and adalimumab in a single-center cohort of
      patients with Crohn's disease.
AB  - BACKGROUND AND AIMS: Patients with Crohn's disease (CD) may need anti
      inflammatory drugs for decades. Anti-TNF-alpha agents have good efficacy and
      adverse events similar to placebo in randomized controlled trials (RCTs), but
      there are still questions about long-term safety and efficacy. In this respect,
      reports from clinical practice may be useful. We currently report on the clinical
      experience with infliximab and adalimumab in a single-center cohort of patients
      with CD. MATERIAL AND METHODS: Patients with CD treated with infliximab or
      adalimumab from 2000 to 2010 were reviewed. Patient and disease characteristics
      at start, reason for discontinuation, and adverse events were recorded
      retrospectively. Corticosteroid use, the need for hospitalization, and surgeries
      before and during anti-TNF-alpha therapy were recorded. RESULTS: Eighty-three
      patients had received anti-TNF-alpha treatment against CD, median treatment
      duration was 11.4 months (0.2-99.5), and follow-up time 59 months (8-135).
      Eighteen of 43 patients using corticosteroids at treatment start discontinued
      corticosteroids during TNF-alpha therapy. Need for hospitalizations (6.13 vs.
      3.28 days/year, p < 0.001) and surgeries (0.56 vs. 0.16 operations/year, p <
      0.001) were lower during anti-TNF-alpha therapy than before treatment. Twenty-six
      percent discontinued therapy due to adverse events and 26% due to lack or loss of
      response. Two of four deaths observed during follow-up were believed to be
      related to anti-TNF-alpha treatment. CONCLUSIONS: Anti-TNF-alpha therapy was
      beneficial in many patients with CD, but the majority of patients discontinued
      treatment during follow-up. Reports from clinical experience with anti-TNF-alpha
      treatment may be valuable for clinicians treating patients with CD.

PMID- 22472027
TI  - Total synthesis of the proposed structure of aldingenin B.
AB  - The first enantioselective total synthesis of the proposed structure of
      aldingenin B is reported in 16 steps from known compounds. The stereochemistry at
      C5 and C6 were established by an asymmetric acetal aldol. Following a ring
      closing metathesis, a selective, substrate-controlled hydrogen bond-mediated
      dihydroxylation provided control of the C2 and C3 stereocenters. Discrepancies in
      the spectroscopic data of the synthetic and natural material led to the
      conclusion that the structure of the natural sample was misassigned.

PMID- 22472028
TI  - Impaired endothelial function in pediatric patients with turner syndrome and
      healthy controls: a case-control study.
AB  - BACKGROUND: Turner Syndrome women are at high risk of vascular disease and the
      assessment of early risk factors in Turner Syndrome girls is an emerging focus of
      research. Our objective was to evaluate endothelial function (EF), a preclinical
      measure of atherosclerosis, in Turner Syndrome girls compared with controls.
      METHODS: A cross-sectional case-control study of Turner Syndrome girls and
      healthy controls. Subjects underwent fasting insulin and glucose with calculation
      of HOMA-IR, fasting lipid profile, anthropometrics, and EF testing using
      peripheral arterial tonometry (PAT). Subjects, aged 10-18 years, had karyotype
      confirmed Turner Syndrome; growth hormone (GH), thyroxine and estrogen use were
      not exclusion criteria. Controls were age- and BMI-matched healthy girls. Fifteen
      Turner Syndrome and 15 controls were recruited. RESULTS: Turner Syndrome girls
      had lower height, higher HDL and higher waist:height ratio than controls. PAT
      hyperemia ratio (RH-PAT) scores were lower in Turner Syndrome (1.64 +/- 0.34 vs.
      2.08 +/- 0.32, p = 0.002) indicating impaired EF. Among Turner Syndrome, RH-PAT
      did not vary with estrogen therapy or with karyotype 45,XO compared with other
      karyotypes. However, endothelial function was better in GH-treated compared with
      GH-untreated Turner Syndrome (1.80 +/- 0.36 vs. 1.4 + 0.22, p = 0.02) although
      there were no differences in HOMA-IR, adiponectin or IGF-1. CONCLUSION: Girls
      with Turner Syndrome exhibit impaired endothelial function compared with
      controls, which may explain higher risk for vascular disease. GH may protect
      endothelial function in Turner Syndrome.

PMID- 22472029
TI  - Wrapper feature selection for small sample size data driven by complete error
      estimates.
AB  - This paper focuses on wrapper-based feature selection for a 1-nearest neighbor
      classifier. We consider in particular the case of a small sample size with a few
      hundred instances, which is common in biomedical applications. We propose a
      technique for calculating the complete bootstrap for a 1-nearest-neighbor
      classifier (i.e., averaging over all desired test/train partitions of the data).
      The complete bootstrap and the complete cross-validation error estimate with
      lower variance are applied as novel selection criteria and are compared with the
      standard bootstrap and cross-validation in combination with three optimization
      techniques - sequential forward selection (SFS), binary particle swarm
      optimization (BPSO) and simplified social impact theory based optimization
      (SSITO). The experimental comparison based on ten datasets draws the following
      conclusions: for all three search methods examined here, the complete criteria
      are a significantly better choice than standard 2-fold cross-validation, 10-fold
      cross-validation and bootstrap with 50 trials irrespective of the selected output
      number of iterations. All the complete criterion-based 1NN wrappers with SFS
      search performed better than the widely-used FILTER and SIMBA methods. We also
      demonstrate the benefits and properties of our approaches on an important and
      novel real-world application of automatic detection of the subthalamic nucleus.

PMID- 22472030
TI  - Simultaneous occurrence of papulonecrotic tuberculid and erythema induratum in a
      patient with pulmonary tuberculosis.
AB  - Although papulonecrotic tuberculid is an uncommon cutaneous manifestation of
      tuberculosis (TB) associated with Mycobacterium tuberculosis infection, the
      simultaneous occurrence of papulonecrotic tuberculid and erythema induratum is
      even rarer. Papulonecrotic tuberculid occurs predominantly in young adults and is
      characterized by eruptions of necrotizing papules that heal with varioliform
      scars. Histopathologic findings include wedge-shaped necrosis of the dermis,
      poorly formed granulomatous infiltration, and vasculitis. Stainings and culture
      for acid-fast bacilli from skin biopsies are usually negative for M.
      tuberculosis, although the eruptions resolve with antitubercular therapy. Few
      patients with papulonecrotic tuberculid, especially with concurrent occurrence of
      erythema induratum, have been reported in the English literature. Here we report
      a case of a 12-year-old girl with simultaneous occurrence of papulonecrotic
      tuberculid and erythema induratum accompanying pulmonary TB.

PMID- 22472031
TI  - Speech-language pathologists' assessment and intervention practices with
      multilingual children.
AB  - Within predominantly English-speaking countries such as the US, UK, Canada, New
      Zealand, and Australia, there are a significant number of people who speak
      languages other than English. This study aimed to examine Australian speech
      language pathologists' (SLPs) perspectives and experiences of multilingualism,
      including their assessment and intervention practices, and service delivery
      methods when working with children who speak languages other than English. A
      questionnaire was completed by 128 SLPs who attended an SLP seminar about
      cultural and linguistic diversity. Approximately one half of the SLPs (48.4%)
      reported that they had at least minimal competence in a language(s) other than
      English; but only 12 (9.4%) reported that they were proficient in another
      language. The SLPs spoke a total of 28 languages other than English, the most
      common being French, Italian, German, Spanish, Mandarin, and Auslan (Australian
      sign language). Participants reported that they had, in the past 12 months,
      worked with a mean of 59.2 (range 1-100) children from multilingual backgrounds.
      These children were reported to speak between two and five languages each; the
      most common being: Vietnamese, Arabic, Cantonese, Mandarin, Australian Indigenous
      languages, Tagalog, Greek, and other Chinese languages. There was limited overlap
      between the languages spoken by the SLPs and the children on the SLPs' caseloads.
      Many of the SLPs assessed children's speech (50.5%) and/or language (34.2%)
      without assistance from others (including interpreters). English was the primary
      language used during assessments and intervention. The majority of SLPs always
      used informal speech (76.7%) and language (78.2%) assessments and, if
      standardized tests were used, typically they were in English. The SLPs sought
      additional information about the children's languages and cultural backgrounds,
      but indicated that they had limited resources to discriminate between speech and
      language difference vs disorder.

PMID- 22472032
TI  - Does mode of administration affect health-related quality-of-life outcomes after
      stroke?
AB  - Telephone interviews and postal surveys may be a resource-efficient way of
      assessing health-related quality-of-life post-stroke, if they produce data
      equivalent to face-to-face interviews. This study explored whether telephone
      interviews and postal surveys of the Stroke and Aphasia Quality of Life Scale
      (SAQOL-39g) yielded similar results to face-to-face interviews. Participants
      included people with aphasia and comprised two groups: group one (n =22) were 3-6
      months post-stroke; group two (n =26) were >=1 year post-stroke. They completed
      either a face-to-face and a telephone interview or a face-to-face interview and a
      postal survey of the SAQOL-39g. Response rates were higher for group two (87%)
      than for group one (72-77%). There were no significant differences between
      respondents and non-respondents on demographics, co-morbidities, stroke severity,
      or communication impairment. Concordance between face-to-face and telephone
      administrations (.90-.98) was excellent; and very good-excellent between face-to
      face and postal administrations (.84-.96), although scores in postal
      administrations were lower (significant for psychosocial domain and overall SAQOL
      39g in group two). These findings suggest that the SAQOL-39g yields similar
      results in different modes of administration. Researchers and clinicians may
      employ alternative modes, particularly in the longer term post-stroke, in order
      to reduce costs or facilitate clients with access difficulties.

PMID- 22472033
TI  - Living with aphasia: three Indigenous Australian stories.
AB  - The incidence of cardiovascular disorders and stroke in Australian Aboriginal
      communities is more than twice as high as non-Indigenous Australians.
      Approximately 30% of people who survive stroke are left with some level of
      aphasia, and yet Indigenous Australians appear to be infrequent users of speech
      language pathology services, and there is virtually no research literature about
      the experiences of aphasia for this group of people. This paper presents the
      stories of living with aphasia for three Indigenous Australian men living in
      Perth, Western Australia. Their narratives were collected by an Indigenous
      researcher through in-depth, supported interviews, and were explored using both
      within-case and cross-case analyses for common and recurring themes. It is argued
      that there is value for speech-language pathologists, and other health
      professionals, to be aware of the broad experiences of living with aphasia for
      Indigenous Australians because their stories are rarely heard and because, as
      with people with aphasia generally, they are at risk of social isolation and tend
      to lack visibility in the community. This study explores the key issues which
      emerge for these three men and highlights the need for further research in this
      area.

PMID- 22472034
TI  - Expression of MMPs and TIMP-1 in smoker and nonsmoker chronic periodontitis
      patients before and after periodontal treatment.
AB  - BACKGROUND AND OBJECTIVE: Nonsurgical periodontal treatment controls periodontal
      inflammation. Matrix metalloproteinases (MMPs) and their tissue inhibitors
      (TIMPs) are implicated both in the destruction and in the healing of periodontal
      tissues. The aim of the present study was to compare the mRNA expression of MMP
      1, -3, -8, -9 and -13 and TIMP-1 in chronic periodontitis before and after
      initial periodontal treatment. MATERIAL AND METHODS: Ninety gingival samples were
      harvested from 30 patients with chronic periodontitis (15 nonsmokers and 15
      smokers) before and after nonsurgical treatment and from 30 periodontally healthy
      control subjects (15 nonsmokers and 15 smokers). Clinical parameters were
      assessed before and after treatment. Total RNA was isolated, and mRNA expression
      of MMPs and TIMP-1 was assessed by RT-PCR. RESULTS: Periodontal treatment
      significantly increased TIMP-1 expression and decreased the ratios of MMPs/TIMP
      1. Post-treatment, nonsmokers with periodontitis had significantly higher MMP-8
      and TIMP-1 expression than healthy nonsmokers, and smokers with periodontitis had
      significantly higher MMP-13 and TIMP-1 expressions than healthy smokers. Post
      treatment, smokers had significantly higher TIMP-1 expression and lower MMP
      8/TIMP-1 ratio than nonsmokers. Post-treatment, there was no correlation among
      MMPs, and the expression of MMPs and TIMP-1 was not correlated with clinical
      measurements. CONCLUSION: Periodontal treatment increased TIMP-1 expression and
      decreased the ratios of MMPs/TIMP-1 in chronic periodontitis. The post-treatment
      increase in TIMP-1 expression was higher for smokers. The TIMP-1 expression was
      higher post-treatment than in health. Post-treatment, MMP-8 expression was higher
      in nonsmokers with periodontitis than in healthy nonsmokers, whereas MMP-13
      expression was higher in smokers with periodontitis than in healthy smokers.

PMID- 22472035
TI  - Phase I/II trial evaluating carbon ion radiotherapy for the treatment of
      recurrent rectal cancer: the PANDORA-01 trial.
AB  - BACKGROUND: Treatment standard for patients with rectal cancer depends on the
      initial staging and includes surgical resection, radiotherapy as well as
      chemotherapy. For stage II and III tumors, radiochemotherapy should be performed
      in addition to surgery, preferentially as preoperative radiochemotherapy or as
      short-course hypofractionated radiation. Advances in surgical approaches,
      especially the establishment of the total mesorectal excision (TME) in
      combination with sophisticated radiation and chemotherapy have reduced local
      recurrence rates to only few percent. However, due to the high incidence of
      rectal cancer, still a high absolute number of patients present with recurrent
      rectal carcinomas, and effective treatment is therefore needed.Carbon ions offer
      physical and biological advantages. Due to their inverted dose profile and the
      high local dose deposition within the Bragg peak precise dose application and
      sparing of normal tissue is possible. Moreover, in comparison to photons, carbon
      ions offer an increase relative biological effectiveness (RBE), which can be
      calculated between 2 and 5 depending on the cell line as well as the endpoint
      analyzed.Japanese data on the treatment of patients with recurrent rectal cancer
      previously not treated with radiation therapy have shown local control rates of
      carbon ion treatment superior to those of surgery. Therefore, this treatment
      concept should also be evaluated for recurrences after radiotherapy, when dose
      application using conventional photons is limited. Moreover, these patients are
      likely to benefit from the enhanced biological efficacy of carbon ions. METHODS
      AND DESIGN: In the current Phase I/II-PANDORA-01-Study the recommended dose of
      carbon ion radiotherapy for recurrent rectal cancer will be determined in the
      Phase I part, and feasibilty and progression-free survival will be assessed in
      the Phase II part of the study.Within the Phase I part, increasing doses from 12
      * 3 Gy E to 18 * 3 Gy E will be applied.The primary endpoint in the Phase I part
      is toxicity, the primary endpoint in the Phase II part is progression-free
      survival. DISCUSSION: With conventional photon irradiation treatment of recurrent
      rectal cancer is limited, and the clinical effect is only moderate. With carbon
      ions, an improved outcome can be expected due to the physical and biological
      characteristics of the carbon ion beam. However, the optimal dose applicable in
      this clincial situation as re-irradiation still has to be determined. This, as
      well as efficacy, is to be evaluated in the present Phase I/II trial. TRIAL
      REGISTRATION: NCT01528683.

PMID- 22472036
TI  - Life-course origins of social inequalities in adult immune cell markers of
      inflammation in a developing southern Chinese population: the Guangzhou Biobank
      Cohort Study.
AB  - BACKGROUND: Socioeconomic position (SEP) throughout life is associated with
      cardiovascular disease, though the mechanisms linking these two are unclear. It
      is also unclear whether there are critical periods in the life course when
      exposure to better socioeconomic conditions confers advantages or whether SEP
      exposures accumulate across the whole life course. Inflammation may be a
      mechanism linking socioeconomic position (SEP) with cardiovascular disease. In a
      large sample of older residents of Guangzhou, in southern China, we examined the
      association of life course SEP with inflammation. METHODS: In baseline data on
      9,981 adults (>= 50 years old) from the Guangzhou Biobank Cohort Study (2006-08),
      we used multivariable linear regression and model fit to assess the associations
      of life course SEP at four stages (childhood, early adult, late adult and
      current) with white blood, granulocyte and lymphocyte cell counts. RESULTS: A
      model including SEP at all four life stages best explained the association of
      life course SEP with white blood and granulocyte cell count for men and women,
      with early adult SEP (education) making the largest contribution. A critical
      period model best explained the association of life course SEP with lymphocyte
      count, with sex-specific associations. Early adult SEP was negatively associated
      with lymphocytes for women. CONCLUSIONS: Low SEP throughout life may negatively
      impact late adult immune-inflammatory status. However, some aspects of immune
      inflammatory status may be sensitive to earlier exposures, with sex-specific
      associations. The findings were compatible with the hypothesis that in a
      developing population, upregulation of the gonadotropic axis with economic
      development may obscure the normally protective effects of social advantage for
      men.

PMID- 22472037
TI  - Effects of pistachios on body weight in Chinese subjects with metabolic syndrome.
AB  - BACKGROUND: Studies have shown that pistachios can improve blood lipid profiles
      in subjects with moderate hypercholesterolemia which could reduce the risk of
      cardiovascular disease. However, there is also a widely perceived view that
      eating nuts can lead to body weight gain due to their high fat content. PURPOSE:
      To investigate the impact of different dosages of pistachios on body weight,
      blood pressure, blood lipids, blood glucose and insulin in subjects with
      metabolic syndrome. METHODS: Ninety subjects with metabolic syndrome (consistent
      with 2005 International Diabetes Federation metabolic syndrome standard without
      diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All
      subjects received dietary counseling according to the guidelines of the American
      Heart Association Step I diet. After a 4 week run-in, subjects were randomized to
      consume either the recommended daily serving of 42 g pistachios (RSG), a higher
      daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks.
      RESULTS: Subjects in all three groups were matched at baseline for BMI: DCG 28.03
      +/- 4.3; RSG 28.12 +/- 3.22; and HSG 28.01 +/- 4.51 kg/m2. There were no
      significant changes in body weight or BMI in any groups during the study nor any
      change from baseline at any time point in any group. During the entire study,
      there were no significant differences in waist-to-hip ratio among the groups or
      any change from baseline in any group (DCG -0.00 +/- 0.03, RSG -0.01 +/- 0.02 and
      HSG 0.01 +/- 0.04). There were no significant differences detected among groups
      in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75
      gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h
      after a 75 gm glucose challenge were significantly lower at week 12 compared with
      baseline values in the HSG group (-1.13 +/- 2.58 mmol/L, p = 0.02), and a similar
      trend was noted in the RSG group (-0.77 +/- 2.07 mmol/L, p = 0.06), while no
      significant change was seen in the DCG group (-0.15 +/- 2.27 mmol/L, p = 0.530).
      At the end of study, serum triglyceride levels were significantly lower compared
      with baseline in the RSG group (-0.38 +/- 0.79 mmol/L, p = 0.018), but no
      significant changes were observed in the HSG or DCG groups. CONCLUSION: Despite
      concerns that pistachio nut consumption may promote weight gain, the daily
      ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to
      weight gain or an increase in waist-to-hip ratio in Chinese subjects with
      metabolic syndrome. In addition, pistachio consumption may improve the risk
      factor associated with the metabolic syndrome.

PMID- 22472038
TI  - Intraperitoneal implant of recombinant encapsulated cells overexpressing alpha-L
      iduronidase partially corrects visceral pathology in mucopolysaccharidosis type I
      mice.
AB  - BACKGROUND AIMS: Mucopolysaccharidosis type I (MPS I) is characterized by
      deficiency of the enzyme alpha-L-iduronidase (IDUA) and storage of
      glycosaminoglycans (GAG) in several tissues. Current available treatments present
      limitations, thus the search for new therapies. Encapsulation of recombinant
      cells within polymeric structures combines gene and cell therapy and is a
      promising approach for treating MPS I. METHODS: We produced alginate
      microcapsules containing baby hamster kidney (BHK) cells overexpressing IDUA and
      implanted these capsules in the peritoneum of MPS I mice. RESULTS: An increase in
      serum and tissue IDUA activity was observed at early time-points, as well as a
      reduction in GAG storage; however, correction in the long term was only partially
      achieved, with a drop in the IDUA activity being observed a few weeks after the
      implant. Analysis of the capsules obtained from the peritoneum revealed
      inflammation and a pericapsular fibrotic process, which could be responsible for
      the reduction in IDUA levels observed in the long term. In addition, treated mice
      developed antibodies against the enzyme. CONCLUSIONS: The results suggest that
      the encapsulation process is effective in the short term but improvements must be
      achieved in order to reduce the immune response and reach a stable correction.

PMID- 22472039
TI  - The effect of hormone therapy on women's quality of life in the first year of the
      Estonian Postmenopausal Hormone Therapy trial.
AB  - BACKGROUND: For postmenopausal women, the main reason to start hormone therapy
      (HT) is to reduce menopausal symptoms and to improve quality of life (QOL). The
      aim of this study was to analyse the impact of HT on different aspects of symptom
      experience and QOL during a randomised trial. A total of 1823 postmenopausal
      women were recruited into the Estonian Postmenopausal Hormone Therapy (EPHT)
      trial in 1999-2001. Women were randomised to blind HT, open-label HT, placebo or
      non-treatment arm. After one year in the trial, a questionnaire was mailed and
      1359 women (75%) responded, 686 in the HT arms and 673 in the non-HT arms. Mean
      age at filling in the questionnaire was 59.8 years. The questionnaire included
      Women's Health Questionnaire (WHQ) to assess menopause specific QOL of middle
      aged women together with a 17-item questionnaire on symptoms related to
      menopause, a question about painful intercourse, and a question about women's
      self-rated health. RESULTS: After one year in the trial, fewer women in the HT
      arms reported hot flashes, trouble sleeping, and sweating on the symptom
      questionnaire. According to WHQ, women in the HT arms had fewer vasomotor
      symptoms, sleep problems, and problems with sexual behaviour, but more menstrual
      symptoms; HT had no effect on depression, somatic symptoms, memory,
      attractiveness, or anxiety. A smaller proportion of women reported painful
      intercourse in the HT arms. There were no significant differences between the
      trial arms in women's self-rated subjective health. CONCLUSIONS: The results from
      the EPHT trial confirm that HT is not justified for treating symptoms, other than
      vasomotor symptoms, among postmenopausal women. WHQ proved to be a useful and
      sensitive tool to assess QOL in this age group of women.

PMID- 22472040
TI  - Analysis of inter-fraction setup errors and organ motion by daily kilovoltage
      cone beam computed tomography in intensity modulated radiotherapy of prostate
      cancer.
AB  - BACKGROUND: Intensity-modulated radiotherapy (IMRT) enables a better conformality
      to the target while sparing the surrounding normal tissues and potentially allows
      to increase the dose to the target, if this is precisely and accurately
      determined. The goal of this work is to determine inter-fraction setup errors and
      prostate motion in IMRT for localized prostate cancer, guided by daily
      kilovoltage cone beam computed tomography (kVCBCT). METHODS: Systematic and
      random components of the shifts were retrospectively evaluated by comparing two
      matching modalities (automatic bone and manual soft-tissue) between each of the
      641 daily kVCBCTs (18 patients) and the planning kVCT. A simulated Adaptive
      Radiation Therapy (ART) protocol using the average of the first 5 kVCBCTs was
      tested by non-parametric bootstrapping procedure. RESULTS: Shifts were < 1 mm in
      left-right (LR) and in supero-inferior (SI) direction. In antero-posterior (AP)
      direction systematic prostate motion (2.7 +/- 0.7 mm) gave the major contribution
      to the variability of results; the averages of the absolute total shifts were
      significantly larger in anterior (6.3 +/- 0.2 mm) than in posterior (3.9 mm +/-
      0.2 mm) direction. The ART protocol would reduce margins in LR, SI and anterior
      but not in posterior direction. CONCLUSIONS: The online soft-tissue correction
      based on daily kVCBCT during IMRT of prostate cancer is fast and efficient. The
      large random movements of prostate respect to bony anatomy, especially in the AP
      direction, where anisotropic margins are needed, suggest that daily kVCBCT is at
      the present time preferable for high dose and high gradients IMRT prostate
      treatments.

PMID- 22472041
TI  - Oxovanadium complexes with quinoline and pyridinone ligands: syntheses of the
      complexes and effect of alkyl chains on their apoptosis-inducing activity in
      leukemia cells.
AB  - Vanadium complexes with quinoline ligands (1b-g) and pyridinone ligands (2b-d)
      were synthesized, and the effect of the length and shape of alkyl chains on the
      antiproliferative activity toward U937 cells was studied. For the synthesis of
      the vanadium complexes, quinoline and pyridinone ligands were prepared and then
      treated with VOSO(4) or VO(acac)(2). The vanadyl(IV) complexes were characterized
      by IR, ESR, and UV-vis spectroscopy and elemental analyses. The antiproliferative
      activity of 1a-g toward U937 cells showed little dependence on the length and
      shape of the alkyl chain. In contrast, a good correlation was found between the
      IC(50) values and partition coefficients (logP) values of 2a-c. Among them, 2c
      showed the highest inhibitory activity, and its IC(50) value was smaller than
      that of cisplatin. The apoptosis-inducing ability of 2b and 2c was supported by
      annexin V-propidium iodide staining experiments and agarose gel electrophoresis
      analysis. Inhibitors of caspase-3, -8, and -9 did not affect the
      antiproliferative activity of 2c, indicating that the apoptosis induced by 2c was
      via a caspase-independent pathway.

PMID- 22472042
TI  - Redox-changes associated with the glutathione-dependent ability of the Cu(II)
      GSSG complex to generate superoxide.
AB  - The intracellularly-occurring Cu(I)-glutathione complex (Cu(I)-[GSH](2)) has the
      ability to reduce molecular oxygen into superoxide. Removal of such radicals
      leads to the irreversible conversion of Cu(I)-[GSH](2) into the redox-inactive
      Cu(II)-GSSG complex. The present study addressed the potential of reduced
      glutathione, ascorbate and superoxide to reductively regenerate Cu(I)-[GSH](2)
      from Cu(II)-GSSG, and investigated the redox changes involved in such process.
      Results show that: (i) among the three tested reductants, only GSH is able to
      reduce the Cu(II) bound to GSSG; (ii) during the reduction of Cu(II)-GSSG, a
      Cu(I)-GSSG intermediate would be formed (supported here by Cu(I) and GSSG
      recovery data and by NMR studies); (iii) when GSH is present in a molar excess
      equal or greater than 1:3, the reduction of Cu(II)-GSSG into Cu(I)-[GSH](2) is
      quantitative and complete. Under such conditions, the Cu(II)-GSSG complex
      acquires a superoxide-generating capacity which is identical to that seen with
      the Cu(I)-[GSH](2) complex. Within cells, the concentrations of GSH are at least
      2- to 3-fold order of magnitude higher than those expected for the Cu(II)-GSSG
      complex. Thus, we postulate that the interaction between GSH and Cu(II)-GSSG
      could be seen as a potential mechanism to regenerate continuously the Cu(I)
      [GSH](2) complex and thereby affect the ability of the latter to generate
      superoxide.

PMID- 22472043
TI  - Synthesis and cytotoxic activity evaluation of dihydrocucurbitacin B and
      cucurbitacin B derivatives.
AB  - Two cucurbitacins, dihydrocucurbitacin B (1) and cucurbitacin B (2), which can be
      obtained in large amounts from the roots of Wilbrandia ebracteata and from the
      fruits of Luffa operculata, respectively, were used as starting materials for the
      preparation of a library of 29 semi-synthetic derivatives. The structural changes
      that were performed include the removal, modification or permutation of
      functional groups in rings A and B as well as in the side chain. All new
      semisynthetic compounds, as well as 1 and 2, were tested in vitro for their
      cytotoxic effects on non-small-cell lung cancer cells (A549 cells). Some of these
      compound displayed potent to moderate activity against A549 tumor cells,
      especially those cucurbitacin B derivatives which were modified at ring A.

PMID- 22472044
TI  - Synthesis, structure-activity relationships and biological evaluation of caudatin
      derivatives as novel anti-hepatitis B virus agents.
AB  - A series of caudatin derivatives were synthesized, and their anti-hepatitis B
      virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the 3-O
      substituted caudatin derivatives showed effective anti-HBV activity. Among the
      tested compounds, six compounds (2e-2h, 2l, 2r) exhibited significantly
      inhibitory activity against HBV DNA replication with IC(50) values in the range
      of 2.82-7.48 MUM. Interestingly, two compounds (2e, 2f) had potent activity
      inhibiting not only the secretion of HBsAg (IC(50)=18.68 MUM, 21.71 MUM), HBeAg
      (IC(50)=13.16 MUM, 33.73 MUM), but also HBV DNA replication (IC(50)=7.48 MUM,
      3.63 MUM). The structure-activity relationships (SARs) of caudatin derivatives
      had been discussed, which were useful for caudatin derivatives to be explored and
      developed as novel anti-HBV agents.

PMID- 22472045
TI  - Synthesis and anticancer activity of 2-benzylidene indanones through inhibiting
      tubulin polymerization.
AB  - In an attempt to discover a potent and selective anticancer agent, gallic acid
      has been modified to benzylidene indanones as tubulin polymerization inhibitors.
      These compounds were evaluated against several human cancer cell lines and also
      evaluated for inhibition of tubulin polymerase in in vitro assays. Three of the
      analogues exhibited strong cytotoxicity against human cancer cell lines IC(50)=10
      880 nM and also showed tubulin polymerization inhibition (IC(50)=0.62-2.04 MUM).
      Compound 9j, the best candidate of the series was found to be non-toxic in acute
      oral toxicity in Swiss-albino mice up to 1000 mg/kg dose.

PMID- 22472046
TI  - Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl
      benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids.
AB  - A series of berberine-phenyl-benzoheterocyclic (26-29) and tacrine-phenyl
      benzoheterocyclic hybrids (44-46) were synthesised and evaluated as
      multifunctional anti-Alzheimer's disease agents. Compound 44b, tacrine linked
      with phenyl-benzothiazole by 3-carbon spacers, was the most potent AChE inhibitor
      with an IC(50) value of 0.017 MUM. This compound demonstrated similar Abeta
      aggregation inhibitory activity with cucurmin (51.8% vs 52.1% at 20 MUM,
      respectively), indicating that this hybrid is an excellent multifunctional drug
      candidate for AD.

PMID- 22472047
TI  - Comparative study of transplantation of hepatocytes at various differentiation
      stages into mice with lethal liver damage.
AB  - Hepatocyte transplantation utilizing induced pluripotent stem cells (iPSCs) or
      embryonic stem cells (ESCs) has been expected to provide an alternative to liver
      transplantation. However, it remains uncertain precisely which cell type is the
      best suited for cell transplantation. In particular, it is unclear whether mature
      hepatocytes, which have sufficient liver function, or immature hepatic progenitor
      cells, which have a higher proliferative capacity, will provide a better outcome.
      The main objective of this study was to investigate the therapeutic efficacy of
      the transplantation of hepatocytes at various differentiation stages. We utilized
      transgenic mice that expressed diphtheria toxin (DT) receptors under the control
      of an albumin enhancer/promoter. ESC-derived endodermal cells, fetal hepatocytes,
      and adult hepatocytes were transplanted into these mice with experimentally
      induced lethal acute liver injury caused by DT administration. The transplanted
      cells were marked by enhanced green fluorescent protein. We evaluated their
      effects on survival. At 35 days after transplantation, the survival rate of the
      adult hepatocyte-transplanted group (8/20, 40%) was significantly improved in
      comparison to that of the sham-operated group (2/25, 8%), the fetal hepatocyte
      transplanted group (1/20, 5%), and the ESC-derived endodermal cell-transplanted
      group (0/21, 0%). The adult hepatocytes proliferated in the recipient livers and
      replaced a large part of their parenchyma. The transplantation of adult
      hepatocytes for acute liver failure significantly improved the survival rate in
      comparison to that of transplantation of immature cells, thus suggesting that
      ESCs and iPSCs should be differentiated into mature hepatocytes before cell
      transplantation for acute liver failure.

PMID- 22472049
TI  - Synthesis of the bridging framework of phragmalin-type limonoids.
AB  - An efficient synthesis of the octahydro-1H-2,4-methanoindene core of phragmalin
      type limonoids, such as xyloccensins O and P, is reported. The success of the
      synthetic route is predicated on the use of network analysis in the
      retrosynthetic analysis and a Diels-Alder reaction for the synthesis of a key
      hydrindanone derivative.

PMID- 22472050
TI  - Sarcoid flexor tenosynovitis as a single early manifestation of the disease.
AB  - Sarcoid flexor tenosynovitis is rare. Isolated sarcoid tenosynovitis of the index
      finger in a young woman as an early manifestation of the disease is reported.
      Tenosynovectomy was performed as a therapeutic and diagnostic tool, followed by
      systemic corticosteroids. The patient had no signs of relapse 3 years after
      surgery.

PMID- 22472051
TI  - Value of the implantable doppler system in free flap monitoring.

PMID- 22472052
TI  - Positive impact of delayed breast reconstruction on breast-cancer treatment
      related arm lymphoedema.
AB  - BACKGROUND: The study aims to determine the impact of delayed breast
      reconstruction on women with breast-cancer treatment-related lymphoedema after
      mastectomy. METHODS: Twenty women with breast-cancer treatment-related arm
      lymphoedema prospectively requesting breast reconstruction were included between
      January 2002 and June 2009. Lymphoedema volume was calculated for each 5-cm
      segment using the formula for a truncated cone. RESULTS: Three patients underwent
      transverse rectus abdominis myocutaneous flap reconstruction, five received
      pedicled latissimus dorsi myocutaneous flaps associated with a breast implant and
      12 a breast implant (silicone) alone. Median lymphoedema duration at the time of
      breast reconstruction was 21 (interquartile range (IQR): 17-34) months. Breast
      reconstruction was done a median of 30 (IQR: 23-56) months after mastectomy. The
      median lymphoedema volume at medians of 5 (244 ml, IQR: 159-435) and 22 months
      (235 ml, IQR: 146-361) of follow-up after reconstruction compared to that
      measured 6 months before breast reconstruction of 378 ml (IQR: 261-459) were
      significantly lower (p<0.02 for both). Specific lymphoedema treatment, unchanged
      during the study, included manual lymph drainage for all women, elastic sleeves
      for 19 and low-stretch bandages for 14. CONCLUSION: Delayed breast reconstruction
      is feasible for women who have developed lymphoedema after mastectomy for breast
      cancer. Further studies are needed to compare the different breast-reconstruction
      techniques and to determine their ideal timing (immediate or delayed).

PMID- 22472053
TI  - The dual tendon palmaris longus variant causing dynamic median nerve compression
      in the forearm.
AB  - This article describes a variant of palmaris longus muscle resulting in median
      nerve compression in the mid forearm. Although the palmaris longus has several
      well-documented anomalies, these seldom lead to nerve compression. The dual
      tendon, central muscle belly variant observed in this case is the first of its
      kind to be reported causing compressive neuropathy at this level. This is of both
      anatomical and clinical interest as it reminds surgeons of the anatomical
      variations of this unique muscle and presents a new mechanism of nerve
      compression in the forearm.

PMID- 22472054
TI  - Visuohaptic discrimination of 3D gross shape.
AB  - Human sensitivity to 3D gross shape changes was measured for the visual and
      haptic sensory channels. Three volume-invariant affine transformations were
      defined: compressing, shearing and stretching. Participants discriminated a
      reference 3D object (cube or sphere) from its deformed  shape under three
      experimental conditions: visual only (on a computer monitor), haptic only
      (through a point-contact force-feedback device) and visuohaptic simulations. The
      results indicate that vision is more sensitive to gross shape changes than point
      based touch, and that vision dominated  in the visuohaptic condition. In the
      haptic alone condition, thresholds were higher for shearing and stretching than
      for compressing. Thresholds were otherwise similar for the three transformations
      in the vision only or visuohaptic conditions. These trends were similar for the
      two shapes tested.  A second experiment, conducted under similar conditions but
      preventing participants from manipulating object orientations, verified that the
      main conclusion of our research still holds when visual inspection can rely only
      on a single perspective view of the object. Our earlier studies on 3D 
      visuohaptic watermarking showed that the haptic channel is more sensitive to
      surface texture and roughness changes than vision. The thresholds from the
      present and our earlier studies can potentially be used as the upper limits for
      selecting watermark strengths in order to ensure watermark  imperceptibility in a
      3D visuohaptic watermarking system.

PMID- 22472055
TI  - Emergency anticoagulation treatment for cirrhosis patients with portal vein
      thrombosis and acute variceal bleeding.
AB  - OBJECTIVE: To determine the safety and efficacy of anticoagulation treatment for
      portal vein thrombosis in cirrhosis patients with acute variceal bleeding, with
      patient eligibility determined by contrast ultrasonography findings. MATERIALS
      AND METHODS: This prospective study included 23 consecutive cirrhosis patients
      (63.8 +/- 11.8 years old, 12 males and 11 females) with emergency admission for
      acute variceal bleeding with or without portal vein thrombus. Eligibility for
      anticoagulation treatment was determined by positive intra-thrombus enhancement
      on contrast ultrasonography (perflubutane microbubble agent, 0.0075 mL/kg)
      performed before endoscopy. Low-molecular-weight heparin was administered after
      hemostasis was achieved by band ligation. Repeated band ligation or injection
      sclerotherapy combined with argon plasma coagulation was performed for variceal
      disappearance. RESULTS: Hemostasis was achieved in all 10 patients with active
      bleeding. Five of these patients had portal vein thrombus, and all showed
      positive intra-thrombus enhancement on contrast ultrasonography. Anticoagulation
      treatment of these five patients resulted in complete recanalization of the
      portal vein within 2-11 days. There were no significant differences in the number
      of endoscopic treatment sessions or the length of hospital stay between the
      groups with and without thrombosis, and no complications including rebleeding
      were reported. Long term, none of the patients who continued oral anticoagulation
      treatment had recurrence of thrombosis (4/5). Variceal recurrence occurred only
      in the non-thrombosis group (2/18) during the follow-up period (median: 351
      days). CONCLUSIONS: Early anticoagulation treatment in cirrhosis patients with
      portal vein thrombosis and acute variceal bleeding may be safe, tolerated, and
      effective in cases with positive intra-thrombus enhancement on contrast
      ultrasonography.

PMID- 22472056
TI  - Toxicity of various silver nanoparticles compared to silver ions in Daphnia
      magna.
AB  - BACKGROUND: To better understand the potential ecotoxicological impacts of silver
      nanoparticles released into freshwater environments, the Daphnia magna 48-hour
      immobilization test was used. METHODS: The toxicities of silver nitrate, two
      types of colloidal silver nanoparticles, and a suspension of silver nanoparticles
      were assessed and compared using standard OECD guidelines. Also, the swimming
      behavior and visible uptake of the nanoparticles by Daphnia were investigated and
      compared. The particle suspension and colloids used in the toxicity tests were
      well-characterized. RESULTS: The results obtained from the exposure studies
      showed that the toxicity of all the silver species tested was dose and
      composition dependent. Plus, the silver nanoparticle powders subsequently
      suspended in the exposure water were much less toxic than the previously prepared
      silver nanoparticle colloids, whereas the colloidal silver nanoparticles and
      AgNO(3) were almost similar in terms of mortality. The silver nanoparticles were
      ingested by the Daphnia and accumulated under the carapace, on the external body
      surface, and connected to the appendages. All the silver species in this study
      caused abnormal swimming by the D. magna. CONCLUSION: According to the present
      results, silver nanoparticles should be classified according to GHS (Globally
      Harmonized System of classification and labeling of chemicals) as "category acute
      1" to Daphnia neonates, suggesting that the release of nanosilver into the
      environment should be carefully considered.

PMID- 22472057
TI  - The effect of citalopram on chronic stress-induced depressive-like behavior in
      rats through GSK3beta/beta-catenin activation in the medial prefrontal cortex.
AB  - Antidepressant treatments enhance synaptic connectivity in stress-sensitive brain
      regions such as the medial prefrontal cortex (mPFC). The mPFC plays a key role in
      controlling cognition and emotion. While several signaling pathways are involved
      in this enhancement process, the exact mechanisms are not fully established. In
      the present study, we evaluated the role of the glycogen synthase kinase 3beta
      (GSK3beta)/beta-catenin signaling pathway in the antidepressant effect of
      citalopram in rats exposed to forced swim stress. The acute stress group received
      the classic, two-day variant of the forced swimming test (FST), whereas the
      chronic stress group received swim stress for 14 consecutive days. We found that
      rats exposed to acute swim stress showed depressive-like behaviors and expressed
      normal GSK3beta and beta-catenin levels in the mPFC. Chronic swim stress, also
      induced a significant behavior changes but was associated with decreased levels
      of phosphorylated GSK3beta and beta-catenin in the rat's mPFC. Chronic citalopram
      treatment alleviated these behavioral changes in chronically stressed rats and
      normalized the downregulation of GSK3beta/beta-catenin signaling. Our results
      suggest that GSK3beta/beta-catenin signaling plays an important role in chronic
      but not acute stress-related depression and contributes, at least in part, to the
      antidepressant effects of citalopram in distinct brain regions associated with
      mood regulation.

PMID- 22472058
TI  - Localization and characterization of kal 1.a and kal 1.b in the brain of adult
      zebrafish (Danio rerio).
AB  - The gene underlying the X-chromosome-linked Kallmann syndrome KAL-1 has been
      identified for several years, yet its role is still poorly understood. During
      previous research, the KAL.1 orthologs, kal 1.a and kal 1.b, were isolated in
      zebrafish. In the present study, in situ hybridization was used to localize and
      compare the expression of kal 1.a and kal 1.b in the adult zebrafish brain (Danio
      rerio). The kal 1.a and kal 1.b transcription products have a similar
      distribution, both being localized in the olfactory bulb, in the ventral and
      posterior zones of the telencephalic area, hypothalamus, thalamus nuclei, corpus
      cerebelli, and many other nuclei, such as the posterior tuberal, the
      periventricular gray zone of the optic tectum, the periglomerular nucleus, the
      entopeduncular nucleus, parvocellular preoptic nucleus, habenular nucleus
      suprachiasmatic nucleus, magnocellular preoptic nucleus, griseum centrale,
      periventricular nucleus of the posterior tuberculum and the lobus caudallis
      cerebelli. In addition, by double approach of in situ hybridization and
      immunolabeling, it was found that, in telencephalon, the two genes are expressed
      in neurons and oligodendrocytes but they are not astrocytes. Finally, by using a
      proliferation marker, BrdU, kal 1.a and kal 1.b transcripts were shown to be
      clearly detected in a region previously described as an area of adult
      neurogenesis, suggesting that they may be involved in the process. Overall, our
      data provide a consolidated map of expression of kal 1.a and kal 1.b and suggest
      a distinct function of these genes, especially neurogenesis, in an adult context.

PMID- 22472059
TI  - Epithelial immune cell-like transition (EIT): a proposed transdifferentiation
      process underlying immune-suppressive activity of epithelial cancers.
AB  - The immune system plays a key role in eliminating cancer cells in the body.
      However, even in fully immune-competent bodies cancers can evade anti-tumor
      immune action. There is increasing evidence that epithelial cancers can actively
      suppress anti-tumor immune responses by creating an immune-suppressive micro
      environment. It has been reported that epithelial cancers can express immune
      genes/proteins not normally expressed by their parental tissues, including a
      variety of cytokines/receptors, immune transcription factors and Ig motifs in
      cell surface molecules. Recently we observed increased expression of immune
      genes, including immune-suppressive genes, by prostate epithelial cancers. In
      view of the above, we propose that immune-suppressive activity of epithelial
      cancers may stem from their acquisition of immune properties via a
      transdifferentiation process, we term "Epithelial Immune Cell-like Transition"
      (EIT), similar to neuroendocrine-like transdifferentiation of prostate
      adenocarcinoma cells. We propose that the acquired immune properties enable the
      cancer cells to "communicate" with immune cells, leading to suppression of anti
      cancer immune activity in their micro-environment and facilitation of the
      expansion and malignant progression of the disease. Acquired immune properties of
      epithelial cancers, which might be quite common, could provide novel targets for
      reducing cancer-generated immune-suppressive activity and enhancing anti-tumor
      immune activity. This proposed paradigm shift could lead to novel therapeutic
      approaches with improved efficacy and broad application.

PMID- 22472060
TI  - Successful staged hip replacement in septic hip osteoarthritis in osteopetrosis:
      a case report.
AB  - BACKGROUND: Osteopetrosis is a rare, inherited, bone disorder, characterized by
      osteosclerosis, obliteration of the medullary cavity and calcified cartilage. The
      autosomal dominant form is compatible with a normal life span, although fractures
      often result from minimal trauma, due to the pathologic nature of bone.
      Osteomyelitis is common in patients with osteopetrosis because of a reduced
      resistance to infection, attributed to the lack of marrow vascularity and
      impairment of white cell function. Only one case of osteomyelitis of the proximal
      third of the femur has been previously reported, treated with several repeated
      debridements and finally with femoral head resection. Here we present for the
      first time a case of a staged implant of a cementless total hip prosthesis for
      the treatment of a septic hip in femoral neck nonunion in osteopetrosis. CASE
      PRESENTATION: A 36-years-old woman, affected by autosomal dominant osteopetrosis
      was referred to our department because of a septic hip arthritis associated with
      femoral neck septic non-union, with draining fistulas. The infection occurred
      early after a plate osteosynthesis for a closed perthrocanteric fracture of the
      femur and persisted in spite of osteosynthesis removal, surgical debridement and
      external fixation. In our hospital the patient underwent accurate debridement,
      femoral head and greater trochanter resection, preparation of the diaphyseal
      intramedullary canal and implant of an antibiotic-loaded cement spacer. The
      spacer was exchanged after one month, due to infection recurrence and four months
      later, a cementless total hip arthroplasty was implanted, with no clinical and
      laboratory signs of infection recurrence at two years follow-up. CONCLUSIONS: In
      case of hip septic arthritis and proximal femur septic non-union, femoral head
      resection may not be the only option available and staged total hip arthroplasty
      can be considered.

PMID- 22472061
TI  - Crosstalk between HIV and hepatitis C virus during co-infection.
AB  - An estimated one-third of individuals positive for HIV are also infected with
      hepatitis C virus (HCV). Chronic infection with HCV can lead to serious liver
      disease including cirrhosis and hepatocellular carcinoma. Liver-related disease
      is among the leading causes of death in patients with HIV, and individuals with
      HIV and HCV co-infection are found to progress more rapidly to serious liver
      disease than mono-infected individuals. The mechanism by which HIV affects HCV
      infection in the absence of immunosuppression by HIV is currently unknown. In a
      recent article published in BMC Immunology, Qu et al. demonstrated that HIV tat
      is capable of inducing IP-10 expression. Further, they were able to show that HIV
      tat, when added to cells, was able to enhance the replication of HCV.
      Importantly, the increase in HCV replication by tat was found to be dependent on
      IP-10. This work has important implications for understanding the effect HIV has
      on the outcome of HCV infection in co-infected individuals. The findings of Qu et
      al. may inform the design of intervention and treatment strategies for co
      infected individuals.Please see related article:
      http://www.biomedcentral.com/1471-2172/13/15.

PMID- 22472062
TI  - Cardiovascular disease (CVD) limbo: how soon and low should we go to prevent CVD
      in diabetes?

PMID- 22472063
TI  - Metabonomic study of host-phage interaction by nuclear magnetic resonance- and
      statistical total correlation spectroscopy-based analysis.
AB  - We present a method for the qualitative and quantitative study of transient
      metabolic flux of phage infection at the molecular level. The method is based on
      statistical total correlation spectroscopy (STOCSY) and partial least squares
      discriminant analysis (PLS-DA) applied to nuclear magnetic resonance (NMR)
      metabonomic data sets. An algorithm for this type of study is developed and
      demonstrated. The method has been implemented on (1)H NMR data sets of growth
      media in planktonic cultures of  Pseudomonas aeruginosa  infected with
      bacteriophage pf1. Transient metabolic flux of various important metabolites,
      identified by STOCSY and PLS-DA analysis applied to the NMR data set, are
      estimated at various stages of growth. The opportunistic and nosocomial pathogen 
      P. aeruginosa  is one of the best-studied model organism for bacterial biofilms.
      Complete information regarding metabolic connectivity of this system is not
      possible by conventional spectroscopic approach. Our study presents temporal
      comparative (1)H NMR metabonomic analyses of  filamentous phage pf1 infection in
      planktonic cultures of  P. aeruginosa  K strain (PAK). We exemplify here the
      potential of STOCSY and PLS-DA tools to gain mechanistic insight into subtle
      changes and to determine the transient flux associated with metabolites following
      metabolic perturbations resulting from phage infection. Our study has given new
      avenues in correlating existing postgenomic data with current metabonomic results
      in  P. aeruginosa  biofilms research.

PMID- 22472064
TI  - Radiochemoimmunotherapy with intensity-modulated concomitant boost: interim
      analysis of the REACH trial.
AB  - PURPOSE: To evaluate efficacy and toxicity clinical in the intensified treatment
      of locally advanced squamous cell carcinoma of the head and neck (SCCHN) with the
      combination of chemotherapy, the EGFR antibody cetuximab, and intensity-modulated
      radiation therapy (IMRT) in a concomitant boost concept. METHODS: REACH is a
      prospective, bi-centric phase II trial of carboplatin/5-FU and cetuximab weekly
      combined with IMRT. Primary endpoint is locoregional control, secondary endpoints
      include acute radiation effects and adverse events. Evaluation of disease
      response is carried out according to the Response Evaluation Criteria in Solid
      Tumors (RECIST); toxicity is assessed using NCI CTC v 3.0. RESULTS: Treatment was
      tolerated moderately well, acneiforme erythema occurred in 74.1% (grade II/III),
      mucositis grade III in 28.6%, and radiation dermatitis grade III in 14.3%. Higher
      grade side-effects resolved quickly until the first follow-up post treatment.
      Objective response rates were promising with 28.6% CR at first follow-up and
      92.9% thereafter. CONCLUSION: The combination of standard carboplatin/5-FU and
      cetuximab is feasible and results in promising objective response rates. The use
      of an IMRT concomitant boost is practicable in a routine clinical setting
      resulting in only moderate overall toxicity of the regimen. TRIAL REGISTRATION
      NUMBER: ISRCTN87356938.

PMID- 22472065
TI  - Improved frequency resolution for characterization of complex fractionated atrial
      electrograms.
AB  - BACKGROUND: The dominant frequency of the Fourier power spectrum is useful to
      analyze complex fractionated atrial electrograms (CFAE), but spectral resolution
      is limited and uniform from DC to the Nyquist frequency. Herein the spectral
      resolution of a recently described and relatively new spectral estimation
      technique is compared to the Fourier radix-2 implementation. METHODS: In 10
      paroxysmal and 10 persistent atrial fibrillation patients, 216 CFAE were acquired
      from the pulmonary vein ostia and left atrial free wall (977 Hz sampling rate,
      8192 sample points, 8.4 s duration). With these parameter values, in the
      physiologic range of 3-10 Hz, two frequency components can theoretically be
      resolved at 0.24 Hz using Fourier analysis and at 0.10 Hz on average using the
      new technique. For testing, two closely-spaced periodic components were
      synthesized from two different CFAE recordings, and combined with two other CFAE
      recordings magnified 2*, that served as interference signals. The ability to
      resolve synthesized frequency components in the range 3-4 Hz, 4-5 Hz, ..., 9-10
      Hz was determined for 15 trials each (105 total). RESULTS: With the added
      interference, frequency resolution averaged 0.29 +/- 0.22 Hz for Fourier versus
      0.16 +/- 0.10 Hz for the new method (p < 0.001). The misalignment error of
      spectral peaks versus actual values was +/-0.023 Hz for Fourier and +/-0.009 Hz
      for the new method (p < 0.001). One or both synthesized peaks were lost in the
      noise floor 13/105 times using Fourier versus 4/105 times using the new method.
      CONCLUSIONS: Within the physiologically relevant frequency range for
      characterization of CFAE, the new method has approximately twice the spectral
      resolution of Fourier analysis, there is less error in estimating frequencies,
      and peaks appear more readily above the noise floor. Theoretically, when
      interference is not present, to resolve frequency components separated by 0.10 Hz
      using Fourier analysis would require an 18.2 s sequence duration, versus 8.4 s
      with the new method.

PMID- 22472066
TI  - Synergistic chiral ion pair catalysts for asymmetric catalytic synthesis of
      quaternary alpha,beta-diamino acids.
AB  - The combination of a chiral phosphate anion with a silver ion has been
      demonstrated as a powerful and synergistic ion pair catalyst for the aza-Mannich
      reaction. A series of valuable quaternary alpha,beta-diamino acid derivatives was
      obtained in high yield, and with excellent diastereo- (up to 25:1 dr) and
      enantioselectivity (up to 99% ee). The adducts can be smoothly transformed into
      the corresponding protected chiral quaternary alpha,beta-diamino acids by a one
      pot hydrolysis reaction.

PMID- 22472067
TI  - Congenital malformations among newborns admitted in the neonatal unit of a
      tertiary hospital in Enugu, South-East Nigeria--a retrospective study.
AB  - BACKGROUND: Congenital abnormalities are not uncommon among newborns and
      contribute to neonatal and infant morbidity and mortality. The prevalence and
      pattern of presentation vary from place to place. Many a time the exact etiology
      is unknown but genetic and environmental factors tend to be implicated. METHODS:
      The objective of this study was to determine the prevalence of congenital
      malformations among newborns admitted in a tertiary hospital in Enugu, the nature
      of these abnormalities and the outcome/prognosis. For purposes of this study,
      congenital abnormalities are defined as obvious abnormality of structure or form
      which is present at birth or noticed within a few days after birth. A cross
      sectional retrospective study in which a review of the records of all babies
      admitted in the Newborn Special Care Unit (NBSCU) of the University of Nigeria
      Teaching Hospital (UNTH), Ituku/Ozalla, Enugu over a four year period (January
      2007-April 2011) was undertaken.All babies admitted in the unit with the
      diagnosis of congenital abnormality were included in the study. Information
      extracted from the records included characteristics of the baby, maternal
      characteristics, nature/type of abnormalities and outcome.Data obtained was
      analyzed using SPSS 13. Rates and proportions were calculated with 95% confidence
      interval. The proportions were compared using students T-test. Level of
      significance was set at P < 0.05 RESULTS: Seventeen (17) out of a total of six
      hundred and seven newborn babies admitted in the newborn unit of UNTH over the
      study period (Jan 2007-March 2011) were found to have congenital abnormalities of
      various types, giving a prevalence of 2.8%. Common abnormalities seen in these
      babies were mainly surgical birth defects and included cleft lip/cleft palate,
      neural tube defects (occurring either singly or in combination with other
      abnormalities), limb abnormalities (often in combination with neural tube defects
      of various types), omphalocoele, umbilical herniae, ano-rectal malformations and
      dysmorphism associated with multiple congenital abnormalities. CONCLUSIONS: The
      results of this study show that 2.8% of babies admitted to a Newborn Special Care
      Unit in a teaching hospital in Enugu had congenital abnormalities and that the
      commonest forms seen were mainly surgical birth defects and includes cleft
      lip/cleft palate and neural tube defects.

PMID- 22472068
TI  - Dialysis in public and private hospitals in Queensland.
AB  - BACKGROUND: Clinical outcomes for patients treated in public and private
      hospitals may be different. AIM: The aim of the study was to compare the
      characteristics and outcomes of patients receiving dialysis at public and private
      hospitals in Queensland. METHODS: Incident adult dialysis patients in Queensland
      registered with the Australia and New Zealand Dialysis and Transplant Registry
      between 1999 and 2009 were classified by dialysis modality at either a public or
      private hospital. Outcomes were dialysis patient characteristics and survival.
      RESULTS: Three thousand, three hundred and ten patients commenced dialysis in
      public hospitals, 1939 haemodialysis (HD) and 1371 peritoneal dialysis (PD).
      Seven hundred and ninety-three patients commenced dialysis in private hospitals,
      757 HD and 36 PD. Compared with public HD, private HD patients were older, had
      more coronary artery disease and less diabetes, and were more likely to live in
      an urban area. Public HD patients were more likely to be obese and referred late
      to a nephrologist. Nearly all indigenous patients were managed in public
      hospitals. Private patients were more likely to have an arteriovenous fistula or
      graft at first HD (P < 0.001) but not after excluding late referrals (P = 0.09).
      Public hospitals provided longer HD sessions and more HD hours per week for all
      age groups except 75+ years. Compared with public hospital HD, patient survival
      adjusted for multiple variables was comparable for private hospital HD (hazard
      ratio 1.20 (95% confidence interval 0.98-1.46, P = 0.07)) but worse for public PD
      (hazard ratio 1.14 (95% confidence interval 1.05-1.24, P = 0.002)). CONCLUSION:
      Private HD patients are older and less likely to be diabetic than public
      patients. Patient survival is worse for public PD than public HD.

PMID- 22472069
TI  - Transurethral bipolar plasmakinetic resection combined with 2 MUm continuous wave
      laser vaporization: a new method for the treatment of large volume benign
      prostatic hyperplasia.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficiency of
      transurethral bipolar plasmakinetic resection of the prostate (PKRP) combined
      with 2 MUm laser vaporization in the management of large prostates (>80 mL).
      BACKGROUND DATA: The safety and efficiency of transurethral vaporesection of the
      prostate with benign prostatic hyperplasia (BPH), using a 2 MUm laser system,
      have been verified. However, this method does still not manage large volume
      prostates efficiently. METHODS: From October 2009 to June 2010, 120 BPH patients
      with a median prostatic volume of 106.7 (+/-16.7) mL (range, 82.5-156.8 mL) were
      randomized for surgical treatment with PKRP combined with 2 MUm laser
      vaporization (n=58) or PKRP only (n=62). All patients were preoperatively
      assessed with subjective symptoms score. Preoperative and perioperative
      parameters at 3-, 6-, and 9-month follow-up were also evaluated. All
      complications were recorded. RESULTS: PKRP combined with 2 MUm laser vaporization
      was significantly superior to PKRP alone in terms of operative time, irrigation
      time, catheterization time, hospital stay, and hemoglobin decrease. The blood
      transfusion and urinary tract infection observed in the PKRP combined with 2 MUm
      laser vaporization group was significantly less than that of the groups that
      received PKRP only. Both groups were similar with respect to resected tissue
      weight, transient incontinence, urethral stricture and retrograde ejaculation in
      the postoperative period. Both groups showed a significant improvement from
      baseline in terms of International Prostate Symptom Score (IPSS), quality of life
      (QOL), maximum urinary flow rate (Qmax), and pulmonary vascular resistance unit
      (PVRU) values. However, no significant difference was found between them.
      CONCLUSIONS: PKRP combined with 2 MUm laser vaporization, which combines the
      advantages of both PKRP and 2 MUm laser, is superior for its shorter operation
      time, less bleeding, and better efficiency. It may be a safer and more effective
      method for the treatment of BPH in large prostates.

PMID- 22472070
TI  - Prognostic factors and outcomes of patients with hepatocellular carcinoma in non
      cirrhotic liver.
AB  - OBJECTIVES: To report the outcome of patients with hepatocellular carcinoma (HCC)
      in non-cirrhotic liver depending on the mode of primary treatment and to define
      clinicopathological factors influencing patients' prognosis. METHODS: A
      retrospective analysis of an unselected cohort of 105 patients was performed.
      Overall survival (OS) was estimated by the Kaplan-Meier method and potentially
      prognostic factors were analyzed in Cox regression models. RESULTS: OS of the
      whole cohort at 1, 3, and 5 years was 66%, 47%, and 29%, respectively. Tobacco
      consumption, ECOG >0, macroscopic vascular invasion, continuous tumor diameter,
      and treatment other than resection were predictors of decreased OS in the whole
      cohort. Resection was performed in 64% of patients with 1-, 3-, and 5-year OS
      rates of 84%, 69%, and 42%, respectively. Siderosis and BCLC stage were
      associated with decreased OS after resection. Recurrence occurred in 57% of
      patients with 1-, 3-, and 5-year disease-free survival (DFS) rates of 63%, 39%,
      and 31%, respectively. Viral hepatitis and macroscopic vascular invasion were
      associated with decreased DFS. One-, 3-, and 5-year OS rates in patients with non
      surgical approaches (transarterial chemoembolization, systemic therapy, best
      supportive care) were 38%, 11%, and 7%, respectively. Tobacco consumption and
      Okuda stage were associated with decreased OS in these patients. CONCLUSIONS: OS
      and DFS of patients with HCC in non-cirrhotic liver depend most notably on tumor
      related, demographic, and etiological factors. Features of the non-neoplastic
      liver tissue play only a minor role. Liver resection leads to a significantly
      better prognosis than non-surgical treatment approaches.

PMID- 22472072
TI  - Modified mattress suturing technique for correcting the septal high dorsal
      deviation around the keystone area.
AB  - BACKGROUND: High dorsal deflection of the nasal septum around the bony
      cartilaginous junction ("keystone area") is often missed and difficult to treat
      because of the importance of septal support. This study introduces a new
      technique of septoplasty to correct this dorsal deviation. METHODS: Forty-two
      patients with severe dorsal septal deviation around the bony-cartilaginous
      junction were included in the study. The surgical process was as follows: after
      elevation of mucoperichondrial flap, deflected bony septum and surplus cartilage
      were removed. Then, partial thickness scorings were performed on the concave side
      of the deviated cartilaginous septum. For correcting the dorsal deviation around
      bony-cartilaginous junction, greenstick fracture and two suture holes were made
      at higher bony septum. Modified mattress suture was performed across the
      deflected bony-cartilaginous junction while pushing the deviated septum to the
      midline gently. Subjective and objective improvements were evaluated with
      questionnaires and acoustic rhinometry at least 3 months after the surgery.
      RESULTS: Significant improvements in nasal obstruction (4.61-2.42) and discomfort
      (1.82-1.39) were achieved. On acoustic rhinometry, cross-sectional area (CSA(1);
      0.41 +/- 0.18 to 0.64 +/- 0.22 cm(2)) and CSA(2) (0.83 +/- 0.37 to 1.39 +/- 0.36
      cm(2)) at the narrower sides showed significant improvements and the ratio of the
      wider to narrower sides in CSA(1) (2.61 +/- 1.91 to 1.47 +/- 0.61) and CSA(2)
      (2.07 +/- 1.51 to 1.33 +/- 0.40) showed significant improvements. CONCLUSION: The
      proposed "modified mattress suture technique" provides positive initial results
      for correction of the high dorsal deviation of septum around the bony
      cartilaginous junction.

PMID- 22472071
TI  - Human telomerase reverse transcriptase and glucose-regulated protein 78 increase
      the life span of articular chondrocytes and their repair potential.
AB  - BACKGROUND: Like all mammalian cells, normal adult chondrocytes have a limited
      replicative life span, which decreases with age. To facilitate the therapeutic
      use of chondrocytes from older donors, a method is needed to prolong their life
      span. METHODS: We transfected chondrocytes with hTERT or GRP78 and cultured them
      in a 3-dimensional atelocollagen honeycomb-shaped scaffold with a membrane seal.
      Then, we measured the amount of nuclear DNA and glycosaminoglycans (GAGs) and the
      expression level of type II collagen as markers of cell proliferation and
      extracellular matrix formation, respectively, in these cultures. In addition, we
      allografted this tissue-engineered cartilage into osteochondral defects in old
      rabbits to assess their repair activity in vivo. RESULTS: Our results showed
      different degrees of differentiation in terms of GAG content between chondrocytes
      from old and young rabbits. Chondrocytes that were cotransfected with hTERT and
      GRP78 showed higher cellular proliferation and expression of type II collagen
      than those of nontransfected chondrocytes, regardless of the age of the cartilage
      donor. In addition, the in vitro growth rates of hTERT- or GRP78-transfected
      chondrocytes were higher than those of nontransfected chondrocytes, regardless of
      donor age. In vivo, the tissue-engineered cartilage implants exhibited strong
      repairing activity, maintained a chondrocyte-specific phenotype, and produced
      extracellular matrix components. CONCLUSIONS: Focal gene delivery to aged
      articular chondrocytes exhibited strong repairing activity and may be
      therapeutically useful for articular cartilage regeneration.

PMID- 22472073
TI  - Multi-scale strategies for the monitoring of freshwater cyanobacteria: reducing
      the sources of uncertainty.
AB  - Cyanobacterial blooms are a frequent phenomenon in eutrophic freshwaters
      worldwide and are considered potential hazards to ecosystems and human health.
      Monitoring strategies based on conventional sampling often fail to cover the
      marked spatial and temporal variations in cyanobacterial distribution and
      fluctuating toxin concentrations inherent to cyanobacterial blooms. To deal with
      these problems, we employed a multi-scale approach for the study of a massive
      Microcystis bloom in Tajo River (Spain) utilizing 1) remote sensing techniques,
      2) conventional water sampling and 3) analysis of chemotypical subpopulations.
      Tajo River at the study area is influenced by high temperatures waters diverted
      upstream from a nuclear power plant, the presence of a dam downstream and a high
      nutrient load, which provide optimal conditions for massive cyanobacterial
      proliferation. MERIS imagery revealed high Chl-a concentrations that rarely fell
      below 20 MUg L(-1) and moderate spatiotemporal variations throughout the study
      period (March-November 2009). Although the phytoplanktonic community was
      generally dominated by Microcystis, sampling points highly differed in
      cyanobacterial abundance and community composition. Microcystin (MC)
      concentrations were highly heterogeneous, varying up to 3 orders of magnitude
      among sampling points, exceeding in some cases WHO guideline values for drinking
      and also for recreational waters. The analysis of single colonies by MALDI-TOF MS
      revealed differences in the proportion of MC-producing colonies among points. The
      proportion of toxic colonies showed a highly significant linear correlation with
      total MC: biovolume ratio (r(2) = 0.9; p < 0.001), evidencing that the
      variability in toxin concentrations can be efficiently addressed by simple
      analysis of subpopulations. We propose implementing a multi-scale monitoring
      strategy that allows covering the spatiotemporal heterogeneities in both
      cyanobacterial distribution (remote sensing) and MC concentrations (subpopulation
      analysis) and thereby reduce the main sources of uncertainty in the assessment of
      the risks associated to bloom events.

PMID- 22472074
TI  - Comparisons of plastic responses to irradiance and physiological traits by
      invasive Eupatorium adenophorum and its native congeners.
AB  - To explore the traits contributing to invasiveness of Eupatorium adenophorum and
      to test the relationship between plasticity of these traits and invasiveness, we
      compared E. adenophorum with its two native congeners at four irradiances (10%,
      23%, 40%, and 100%). The invader showed constantly higher performance (relative
      growth rate and total biomass) across irradiances than its native congeners.
      Higher light-saturated photosynthetic rate (P(max)), respiration efficiency (RE),
      and nitrogen (PNUE) and water (WUE, at 40% and 100% irradiances only) use
      efficiencies contributed directly to the higher performance of the invader.
      Higher nitrogen allocation to, stomatal conductance, and the higher contents of
      leaf nitrogen and pigments contributed to the higher performance of the invader
      indirectly through increasing P(max), RE, PNUE and WUE. The invader had
      consistently higher plasticity only in carotenoid content than its native
      congeners in ranges of low (10-40%), high (40-100%) and total (10-100%)
      irradiances, contributing to invasion success in high irradiance by photo
      protection. In the range of low irradiances, the invader had higher plasticity in
      some physiological traits (leaf nitrogen content, nitrogen contents in
      bioenergetics, carboxylation and in light-harvesting components, and contents of
      leaf chlorophylls and carotenoids) but not in performance, while in the ranges of
      high or total irradiances, the invader did not show higher plasticity in any
      variable (except Car). The results indicated that the relationship between
      invasiveness and plasticity of a specific trait was complex, and that a universal
      generalization about the relationship might be too simplistic.

PMID- 22472075
TI  - Abiotic stresses activate a MAPkinase in the model grass species Lolium
      temulentum.
AB  - Forage and turf grasses are utilized in diverse environments that expose them to
      a variety of abiotic stresses, however very little is known concerning the
      perception or molecular responses to these various stresses. In the model grass
      species Lolium temulentum, a 46kDa mitogen-activated protein kinase (MAPK) was
      activated in the leaf within 10min of exposing the roots to salt stress. When
      plants were subjected cold stress, no significant activation of the MAPK was
      observed. However, the 46kDa MAPK was rapidly activated in the leaves of plants
      within 3min of exposure to heat stress. Previously, mechanical wounding has been
      shown to rapidly activate a 46kDa and a 44kDa MAPK in L. temulentum. The wound
      activation of the MAPKs was delayed and diminished in plants undergoing cold
      treatment. In plants subjected simultaneously to 40 degrees C and wounding, the
      activation of the 46kDa MAPK was enhanced. However if plants were subjected to
      heat and cold stress for more than 2h or exposed to 300mM NaCl for 24h prior to
      wounding, the wound activation of the 46kDa and a 44kDa MAPKs were significantly
      inhibited. These results suggest that the 46kDa MAPK plays a role in the response
      to various environmental stimuli.

PMID- 22472076
TI  - Ultrastructural comparison of the compound eyes of Sinopanorpa and Panorpa
      (Mecoptera: Panorpidae).
AB  - The ultrastructure of the compound eyes of scorpionflies Sinopanorpa tincta
      (Navas, 1931), Panorpa liui Hua, 1997 and Panorpa sexspinosa Cheng, 1949 in
      Panorpidae were comparatively investigated using transmission electron
      microscopy. Their compound eyes share the following characters: each ommatidium
      possesses a corneal lens, a eucone tetrapartite crystalline cone surrounded by a
      pair of primary pigment cells, and eight retinula cells. Seven retinula cells (R1
      R7) are in contact with the crystalline cone and extend to the basal lamina, but
      the eighth retinula cell (R8) is only restricted to the basal level of the
      ommatidium. The rhabdomeres of cells R1-R7 form a centrally fused rhabdom that
      almost spans the full length of the ommatidium, and that of R8 only contributes
      to the basal part of the rhabdom. The distal part of the rhabdom projects upward
      into the region between the cone cell tips and force the cone cells to split
      apart into four thin cone cell roots that run along a narrow intercellular gap
      between adjacent retinula cells. The number of secondary pigment cells varies
      from 12 in P. liui to 16 in P. sexspinosa and S. tincta. Based on the
      dissimilarity of the imaginal and larval ommatidial structure, the imaginal
      compound eyes are very unlikely to be directly developed from the larval compound
      eyes in the Panorpidae.

PMID- 22472077
TI  - Profiling of illicit fentanyl using UHPLC-MS/MS.
AB  - Methodology is presented for the profiling of fentanyl in seized drugs using
      ultra high performance liquid chromatography in combination with tandem mass
      spectrometry (UHPLC-MS/MS). Target analysis was performed for 40 fentanyl
      processing impurities, several of which are markers for a specific synthetic
      route (Siegfried or Janssen). For the separation of these solutes, an Acquity BEH
      C18 1.7 MUm particle column (150 mm * 2.1 mm) with a binary 1% formic acid (pH
      2.0)/acetonitrile gradient was used. For MS/MS detection, an atmospheric pressure
      positive electrospray source was employed with selected reaction monitoring
      (SRM). The coupling of the high separation power of UHPLC with the highly
      selective and sensitive detection of MS/MS is amenable to the determination of
      synthetic route and linking of drug seizures. The technology is also applicable
      to exhibits containing trace levels of fentanyl in the presence of significantly
      excess amounts of heroin and/or adulterants.

PMID- 22472078
TI  - Ignitable liquid identification using gas chromatography/mass spectrometry data
      by projected difference resolution mapping and fuzzy rule-building expert system
      classification.
AB  - The gasoline and kerosene collected from different locations in the United States
      were identified by gas chromatography/mass spectrometry (GC/MS) followed by
      chemometric analysis. Classifications based on two-way profiles and target
      component ratios were compared. The projected difference resolution (PDR) mapping
      was applied to measure the differences among the ignitable liquid (IL) samples by
      their GC/MS profiles quantitatively. Fuzzy rule-building expert systems (FuRESs)
      were applied to classify individual ILs. The FuRES models yielded correct
      classification rates greater than 90% for discriminating between samples. PDR
      mapping, a new method for characterizing complex data sets was consistent with
      the FuRES classification result.

PMID- 22472079
TI  - Different matrix attachment regions flanking a transgene effectively enhance gene
      expression in stably transfected Chinese hamster ovary cells.
AB  - Numerous matrix attachment regions (MARs) have been used to improve transgene
      expression in genetic engineering, but an efficient and stable expression vector
      is lacking. In the present study, a vector named pCCF containing chloramphenicol
      acetyltransferase (CAT) reporter gene cassettes was constructed. The cassettes
      were flanked by a beta-interferon MAR at the 5' upstream of the reporter gene
      cassettes, and a beta-globin MAR at the 3' site. After transfecting pCCF into
      Chinese hamster ovary cells, the expression level of the CAT gene with a MAR was
      effectively increased to about 4.5-fold higher than that transfected with pCAM
      (containing two beta-globin MARs flanking the expression cassette), and to 46.4
      fold higher than that transfected with the control plasmid pCAG (without MARs).
      Quantitative reverse transcription polymerase chain reaction and the 2(
      DeltaDeltaCt) method were used to analyze the CAT gene relative copy numbers. The
      expression levels were found to be not directly proportional to the gene copy
      numbers when MAR elements from different sources were used. However, the presence
      of MARs improved the transgene copy numbers.

PMID- 22472080
TI  - Interleukin 2 gene polymorphisms are associated with non-Hodgkin lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy worldwide.
      Interleukin-2 (IL-2) plays a key role in the proliferation of T cells and natural
      killer cells. It has been reported that polymorphisms in the IL-2 gene are
      associated with various cancers. The aim of this study was to examine the effect
      of polymorphisms in the IL-2 gene on the development of NHL in the Chinese
      population. IL-2-330T/G and +114T/G polymorphisms were detected by polymerase
      chain reaction-restriction fragment length polymorphism in 438 NHL cases and 482
      age-matched healthy controls. Data were analyzed using the Chi-square test.
      Results showed that individuals with -330TG genotype or -330GG genotype had
      significantly increased susceptibility to NHL (Odds ratio [OR] = 1.40, 95%
      confidence interval [CI]: 1.05-1.85, p = 0.020 and OR = 2.04, 95%CI: 1.28-3.24, p
      = 0.002). Meanwhile, the +114T/G polymorphism did not show any correlation with
      NHL. When analyzing the haplotypes of these two polymorphisms, the prevalence of 
      330G/+114T haplotype was significantly higher in NHL cases than in controls (OR =
      1.45, 95%CI: 1.12-1.88, p = 0.005). These data indicate that IL-2 gene
      polymorphisms may be new risk factors for NHL.

PMID- 22472081
TI  - T-cell immunoglobulin- and mucin-domain-containing molecule 3 gene polymorphisms
      and renal cell carcinoma.
AB  - T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel
      transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell
      mediated immunity. This study was undertaken to investigate the association of
      TIM-3 polymorphisms with susceptibility to renal cell carcinoma (RCC) in the
      Chinese population. Blood was collected from 322 RCC patients and 402 healthy
      controls. Three polymorphisms in the TIM-3 gene (-1516G/T, -574G/T, and +4259T/G)
      were genotyped by polymerase chain reaction-restriction fragment length
      polymorphism. Results showed that the -574G/T and +4259T/G polymorphisms were
      significantly increased in the RCC cases (odds ratio [OR] = 2.77, 95% confidence
      interval [CI], 1.42-5.39, p = 0.002 and OR = 3.22, 95% CI, 1.64-6.35, p<0.001).
      When analyzing the haplotypes of TIM-3 polymorphisms, TTG (-1516, -574, and
      +4259) revealed a significant correlation with RCC (OR = 3.55, 95% CI, 1.13-11.2,
      p = 0.033). In addition, the prevalence of +4259T/G polymorphism was higher in
      RCC cases with metastasis than in those without metastasis (7.4% vs. 3.5%, p =
      0.041). These results suggest that polymorphisms in the TIM-3 gene are new risk
      factors for RCC and that TIM-3 may play important roles in regulating the
      prognosis of this disease.

PMID- 22472082
TI  - Chlamydia psittaci in ocular adnexa MALT lymphoma: a possible role in
      lymphomagenesis and a different geographical distribution.
AB  - Ocular adnexa MALT-lymphomas represent approximatively 5-15% of all extranodal
      lymphomas. Almost 75% of OAMLs are localized in orbital fat, while 25% of cases
      involves conjunctive. MALT-lymphomas often recognize specific environmental
      factors responsible of lymphoma development and progression. In particular as
      Helicobacter pylori in gastric MALT lymphomas, other bacterial infections have
      been recognized related to MALT lymphomas in specific site. Recently Chlamydia
      psittaci has been identified in Ocular Adnexa MALT lymphomas, with variable
      frequence dependently from geographic areas. Thus bacterial infection is
      responsible of clonal selection on induced MALT with subsequent lymphoma
      development. Moreover Chlamydia psittaci could promote chromosomal aberration
      either through genetic instability as a consequence of induced proliferation and
      probably through DNA oxidative damage. The most common translocation described in
      MALT lymphomas affects NF-kB pathway with a substantial antiapoptotic effect.
      Several therapeutic approaches are now available, but the use of antibiotic
      therapy in specific cases, although with conflicting results, could improve the
      treatment of ocular adnexa MALT lymphomas. In this review we analyse the most
      relevant features of Ocular adnexa MALT lymphomas, underlining specific
      biological characteristics mainly related to the potential role of Chlamydia
      psittaci in lymphomagenesis.

PMID- 22472083
TI  - Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot
      study.
AB  - BACKGROUND: Exposure to endocrine active compounds, including bisphenol A (BPA),
      remains poorly characterized in developing countries despite the fact that
      behavioral practices related to westernization have the potential to influence
      exposure. BPA is a high production volume chemical that has been associated with
      metabolic dysfunction as well as behavioral and developmental effects in people,
      including children. In this pilot study, we evaluate BPA exposure and assess
      likely pathways of exposure among girls from urban and rural Egypt. METHODS: We
      measured urinary concentrations of total (free plus conjugated) species of BPA in
      spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared
      these concentrations to preexisting data from age-matched American girls (N = 47)
      from the U.S. National Health and Nutrition Examination Survey (NHANES). We also
      collected anthropometric and questionnaire data regarding food storage behaviors
      to assess potential routes of exposure. RESULTS: Urban and rural Egyptian girls
      exhibited similar concentrations of urinary total BPA, with median unadjusted
      values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in
      this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly
      lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL)
      according to NHANES 2009-2010 data. Reported storage of food in plastic
      containers was a significant predictor of increasing concentrations of urinary
      BPA. CONCLUSIONS: Despite the relatively low urinary BPA concentrations within
      this Egyptian cohort, the significant association between food storage behaviors
      and increasing urinary BPA concentration highlights the need to understand food
      and consumer product patterns that may be closing the gap between urban and rural
      lifestyles.

PMID- 22472084
TI  - Three-dimensional in vitro tri-culture platform to investigate effects of
      crosstalk between mesenchymal stem cells, osteoblasts, and adipocytes.
AB  - The bone marrow niche for mesenchymal stem cells (MSCs) contains different
      amounts of bone and fat that vary with age and certain pathologies. How this
      dynamic niche environment may affect their differentiation potential and/or
      healing properties for clinical applications remains unknown, largely due to the
      lack of physiologically relevant in vitro models. We developed an enabling
      platform to isolate and study effects of signaling interactions between tissue
      scale, laminated hydrogel modules of multiple cell types in tandem. We applied
      this platform to co- and tri-culture of primary human MSCs, osteoblasts, and
      adipocytes over 18 days in vitro. Each cell type was analyzed separately with
      quantitative polymerase chain reaction (qPCR) and histochemistry for several
      mesenchymal lineage markers. Distinct expression dynamics for osteogenic,
      adipogenic, chondrogenic, and myogenic transcriptional regulators resulted within
      each cell type depending on its culture setting. Incorporating this data into
      multivariate models produced latent identifiers of each emergent cell type
      dependent on its co- or tri-culture setting. Histological staining showed
      sustained triglyceride storage in adipocytes regardless of culture condition, but
      transient alkaline phosphatase activity in both osteoblasts and MSCs. Taken
      together, our results suggest novel emergent phenotypes for MSCs, osteoblasts,
      and adipocytes in bone marrow that are dependent on and result in part from
      paracrine interactions with their neighboring cell types.

PMID- 22472086
TI  - Direct intramyocardial mesenchymal stromal cell injections in patients with
      severe refractory angina: one-year follow-up.
AB  - In patients with stable coronary artery disease (CAD) and refractory angina, we
      performed direct intramyocardial injections of autologous mesenchymal stromal
      cells (MSC) and followed the safety and efficacy of the treatment for 12 months.
      A total of 31 patients with stable CAD, moderate to severe angina, normal left
      ventricular ejection fraction, and no further revascularization options were
      included. Bone marrow MSCs were isolated and culture expanded for 6-8 weeks and
      then stimulated with vascular endothelial growth factor (VEGF) for 1 week. The 12
      month follow-up demonstrated that it was safe to culture expand MSCs and use the
      cells for clinical treatment. The patients' maximal metabolic equivalent (MET)
      during exercise increased from 4.23 MET at baseline to 4.72 MET at 12-month
      follow-up (p < 0.001), Canadian Cardiovascular Society Class (CCS) was reduced
      from 3.0 to 0.8 (p < 0.001), angina attacks per week from 13.8 to 3.2 (p <
      0.001), and nitroglycerin consumption from 10.7 to 3.4 per week (p < 0.001). In
      addition, Seattle Angina Questionnaire (SAQ) evaluations demonstrated highly
      significant improvements in physical limitation, angina stability, angina
      frequency, and quality of life (p < 0.001 for all). It is safe in the
      intermediate/long term to treat patients with stable CAD using autologous culture
      expanded MSCs. Previously reported, early and highly significant improvements in
      exercise capacity and clinical symptoms persist after 12 months. The results are
      encouraging, and a larger controlled study is warranted.

PMID- 22472087
TI  - Antibiotic use and misuse in residential aged care facilities.
AB  - BACKGROUND: The prevention and control of transmission of antimicrobial-resistant
      pathogens in residential aged care facilities (RACF) is an area that has been
      neglected yet has significant implications for health services. AIMS: The aims of
      this study were to describe the prevalence and appropriateness of antibiotic use
      within five RACF associated with our health service. METHODS: Demographic data on
      each RACF and all residents were obtained, and antibiotics prescribed (the type,
      indication and duration) at the time of the survey were recorded. The
      appropriateness of antibiotic prescribing was assessed using well-established
      criteria. RESULTS: Of the 257 residents, 28% were greater than 85 years of age,
      almost 50% were male and 71% had been in their RACF for more than a year. Sixty
      seven per cent were incontinent of urine or faeces, and 80% had some degree of
      cognitive impairment. Among the residents, 23 (9%) were receiving antibiotics at
      the time of the survey. Seventeen (74%) were for treatment, while six (26%) were
      given for prophylactic reasons. Data on the appropriateness of antibiotic use
      were available for the preceding 26-month period. During this time, there were
      988 antibiotic courses administered; of these, 392 (39.7%) did not fulfil the
      criteria for bacterial infection. CONCLUSION: This Australian study is one of the
      first to report on the use of antibiotics within RACF, shows a high rate of
      antimicrobial prescribing and inappropriate antibiotic use. Antibiotic
      stewardship is of paramount importance in RACF. Programmes to promote the
      rational use of antibiotics and minimise the emergence of resistant pathogens are
      urgently required in Australian RACF.

PMID- 22472085
TI  - Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a
      transgenic model of Alzheimer's disease-like amyloid pathology.
AB  - BACKGROUND: A growing body of evidence indicates that inflammation is one of the
      earliest neuropathological events in Alzheimer's disease. Accordingly, we have
      recently shown the occurrence of an early, pro-inflammatory reaction in the
      hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the
      absence of amyloid plaques but associated with intracellular accumulation of
      amyloid beta petide oligomers. The role of such a pro-inflammatory process in the
      progression of the pathology remained to be elucidated. METHODS AND RESULTS: To
      clarify this we administered minocycline, a tetracyclic derivative with anti
      inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP
      mice for one month. The treatment ended at the age of three months, when the mice
      were still devoid of plaques. Minocycline treatment corrected the up-regulation
      of inducible nitric oxide synthase and cyclooxygenase-2 observed in young
      transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers
      correlated with a reduction in amyloid precursor protein levels and amyloid
      precursor protein-related products. Beta-site amyloid precursor protein cleaving
      enzyme 1 activity and levels were found to be up-regulated in transgenic placebo
      mice, while minocycline treatment restored these levels to normality. The anti
      inflammatory and beta-secretase 1 effects could be partly explained by the
      inhibition of the nuclear factor kappa B pathway. CONCLUSIONS: Our study suggests
      that the pharmacological modulation of neuroinflammation might represent a
      promising approach for preventing or delaying the development of Alzheimer's
      disease neuropathology at its initial, pre-clinical stages. The results open new
      vistas to the interplay between inflammation and amyloid pathology.

PMID- 22472088
TI  - Update on resistance status of Anopheles gambiae s.s. to conventional
      insecticides at a previous WHOPES field site, "Yaokoffikro", 6 years after the
      political crisis in Cote d'Ivoire.
AB  - BACKGROUND: At Yaokoffikro field site near Bouake, in central Cote d'Ivoire, a
      group of experimental huts built in 1996 served over many years for the
      evaluation of insecticides against highly resistant mosquitoes. Breeding sites of
      mosquitoes and selection pressure in the area were maintained by local farming
      practices until a war broke out in September 2002. Six years after the crisis, we
      conducted bioassays and biochemical analysis to update the resistance status of
      Anopheles gambiae s.s. populations and detect other potential mechanisms of
      resistance that might have evolved. METHODS: An. gambiae s.s. larvae from
      Yaokoffikro were collected in breeding sites and reared to adults. Resistance
      status of this population to insecticides was assessed using WHO bioassay test
      kits for adult mosquitoes with seven insecticides: two pyrethroids, a pseudo
      pyrethroid, an organochloride, two carbamates and an organophosphate.Molecular
      and biochemical assays were carried out to identify the L1014F kdr and ace-1R
      alleles in individual mosquitoes and to detect potential increase in mixed
      function oxidases (MFO), non-specific esterases (NSE) and glutathione S
      transferases (GST) activity. RESULTS: High pyrethroids, DDT and carbamate
      resistance was confirmed in An. gambiae s.s. populations from Yaokoffikro.
      Mortality rates were less than 70% with pyrethroids and etofenprox, 12% with DDT,
      and less than 22% with the carbamates. Tolerance to fenitrothion was observed,
      with 95% mortality after 24 h.PCR analysis of samples from the site showed high
      allelic frequency of the L1014F kdr (0.94) and the ace-1R (0.50) as before the
      crisis. In addition, increased activity of NSE, GST and to a lesser extent MFO
      was found relative to the reference strain Kisumu. This was the first report
      detecting enhanced activity of these enzymes in An. gambiae s.s from Yaokoffikro,
      which could have serious implications in detoxification of insecticides. Their
      specific roles in resistance should be investigated using additional tools.
      CONCLUSION: The insecticide resistance profile at Yaokoffikro appears
      multifactorial. The site presents a unique opportunity to evaluate its impact on
      the protective efficacy of insecticidal products as well as new tools to manage
      these complex mechanisms. It calls for innovative research on the behaviour of
      the local vector, its biology and genetics that drive resistance.

PMID- 22472089
TI  - Serum anti-Mullerian hormone levels are lower in reproductive-age women with
      Crohn's disease compared to healthy control women.
AB  - BACKGROUND AND AIM: Crohn's disease (CD) decreases fertility both directly, by
      inducing inflammation in the fallopian tubes and ovaries, and indirectly, through
      the surgical interventions and tubal adhesions associated with disease treatment.
      Anti-mullerian hormone (AMH) is a reliable indicator of ovarian reserve in women.
      We aimed to compare serum AMH levels between reproductive-age women with CD and
      healthy controls. METHODS: Serum AMH levels were measured by ELISA in 35 women
      with CD and 35 age-matched healthy women controls. RESULTS: CD patients and
      controls were similar in terms of age, height, weight and BMI. Mean CD duration
      was 60 months. CRP, ESR and leukocyte counts were significantly higher in CD
      patients compared to the controls (p<0.001, p=0.004 and p=0.04, respectively).
      AMH levels in CD patients (1.02 +/- 0.72) were significantly lower compared to
      the controls (1.89 +/- 1.80) (p = 0.009). Serum AMH levels in CD patients with
      active disease (0.33 +/- 0.25) were significantly lower compared to CD patients
      who were in remission (1.53 +/- 0.49) (p = 0.001). Serum AMH levels were similar
      in CD patients with a disease duration of less than 5 years (17 patients) and CD
      patients with a disease duration of greater than 5 years (18 patients) (p = 0.8).
      In CD patients, a negative correlation between CDAI and serum AMH levels was
      found (r = -0.718, p < 0.001). Serum AMH levels were similar in CD patients who
      had (6 patients) and had not undergone (29 patients) surgical treatment (p =
      0.2). CONCLUSION: Serum AMH levels of reproductive-age women with CD were
      significantly lower compared to the controls. CDAI and AMH are inversely
      correlated.

PMID- 22472090
TI  - Tolerability of one hour 10 mg/kg infliximab infusions in patients with
      inflammatory bowel disease.
AB  - BACKGROUND AND AIM: In patients with inflammatory bowel disease (IBD) tolerating
      2-h infusions of 5mg/kg infliximab scheduled maintenance therapy, the infusion
      time can be shortened to 1-h with good tolerability. The tolerability of one 1
      hour 10 mg/kg infliximab infusion in patients with IBD is unknown. METHODS:
      Between August and September 2011, 8 patients received one 1-hour 10mg/kg
      infliximab infusion. All patients were treated in our infusion unit under
      standard operating procedures. Intravenous steroid premedication was given to all
      patients. These 8 patients were compared to 26 IBD patients who received one 1
      hour 5mg/kg infliximab infusion during the same study period at Nancy University
      Hospital. The charts of these 34 patients were reviewed to assess tolerability of
      1-hour infliximab infusions. RESULTS: A total of 34 patients with IBD on
      infliximab maintenance therapy (82.4% Crohn's disease, 17.6% ulcerative colitis;
      22 females) received one 1-hour 5 or 10mg/kg infusion. Four patients were
      receiving concomitant immunomodulators. No severe infusions reactions were
      reported in the 34 IBD patients. Two mild acute reactions (7.7%) and two delayed
      reactions (7.7%) occurred in the 5mg/kg infliximab group. We did not observe any
      acute or delayed infliximab reactions in the 10mg/kg patients group. CONCLUSIONS:
      In patients with inflammatory bowel disease receiving infliximab scheduled
      maintenance therapy, 1-hour infusion time for 10mg/kg infliximab appears to be
      well tolerated. Large prospective studies are needed to confirm our findings.

PMID- 22472091
TI  - Language acquisition for deaf children: Reducing the harms of zero tolerance to
      the use of alternative approaches.
AB  - Children acquire language without instruction as long as they are regularly and
      meaningfully engaged with an accessible human language. Today, 80% of children
      born deaf in the developed world are implanted with cochlear devices that allow
      some of them access to sound in their early years, which helps them to develop
      speech. However, because of brain plasticity changes during early childhood,
      children who have not acquired a first language in the early years might never be
      completely fluent in any language. If they miss this critical period for exposure
      to a natural language, their subsequent development of the cognitive activities
      that rely on a solid first language might be underdeveloped, such as literacy,
      memory organization, and number manipulation. An alternative to speech-exclusive
      approaches to language acquisition exists in the use of sign languages such as
      American Sign Language (ASL), where acquiring a sign language is subject to the
      same time constraints of spoken language development. Unfortunately, so far,
      these alternatives are caught up in an "either - or" dilemma, leading to a highly
      polarized conflict about which system families should choose for their children,
      with little tolerance for alternatives by either side of the debate and
      widespread misinformation about the evidence and implications for or against
      either approach. The success rate with cochlear implants is highly variable. This
      issue is still debated, and as far as we know, there are no reliable predictors
      for success with implants. Yet families are often advised not to expose their
      child to sign language. Here absolute positions based on ideology create
      pressures for parents that might jeopardize the real developmental needs of deaf
      children. What we do know is that cochlear implants do not offer accessible
      language to many deaf children. By the time it is clear that the deaf child is
      not acquiring spoken language with cochlear devices, it might already be past the
      critical period, and the child runs the risk of becoming linguistically deprived.
      Linguistic deprivation constitutes multiple personal harms as well as harms to
      society (in terms of costs to our medical systems and in loss of potential
      productive societal participation).

PMID- 22472093
TI  - Suberitine A-D, four new cytotoxic dimeric aaptamine alkaloids from the marine
      sponge Aaptos suberitoides.
AB  - Suberitine A-D (1-4), four new bis-aaptamine alkaloids with two aaptamine
      skeleton units, 8,9,9-trimethoxy-9H-benzo[de][1,6]-naphthyridine and
      demethyl(oxy)-aaptamine, linked through a rare C-3-C-3' or C-3-C-6' sigma-bond
      between the 1,6-naphthyridine rings, together with two known monomers 5 and 6,
      were isolated from the marine sponge Aaptos suberitoides. Their structures were
      elucidated using NMR spectroscopy. Compounds 2 and 4 showed potent cytotoxicity
      against P388 cell lines, with IC(50) values of 1.8 and 3.5 MUM, respectively.

PMID- 22472092
TI  - Production and validation of a good manufacturing practice grade human fibroblast
      line for supporting human embryonic stem cell derivation and culture.
AB  - INTRODUCTION: The development of reproducible methods for deriving human
      embryonic stem cell (hESC) lines in compliance with good manufacturing practice
      (GMP) is essential for the development of hESC-based therapies. Although
      significant progress has been made toward the development of chemically defined
      conditions for the maintenance and differentiation of hESCs, efficient derivation
      of new hESCs requires the use of fibroblast feeder cells. However, GMP-grade
      feeder cell lines validated for hESC derivation are not readily available.
      METHODS: We derived a fibroblast cell line (NclFed1A) from human foreskin in
      compliance with GMP standards. Consent was obtained to use the cells for the
      production of hESCs and to generate induced pluripotent stem cells (iPSCs). We
      compared the line with a variety of other cell lines for its ability to support
      derivation and self-renewal of hESCs. RESULTS: NclFed1A supports efficient rates
      (33%) of hESC colony formation after explantation of the inner cell mass (ICM) of
      human blastocysts. This compared favorably with two mouse embryonic fibroblast
      (MEF) cell lines. NclFed1A also compared favorably with commercially available
      foreskin fibroblasts and MEFs in promoting proliferation and pluripotency of a
      number of existing and widely used hESCs. The ability of NclFed1A to maintain
      self-renewal remained undiminished for up to 28 population doublings from the
      master cell bank. CONCLUSIONS: The human fibroblast line Ncl1Fed1A, produced in
      compliance with GMP standards and qualified for derivation and maintenance of
      hESCs, is a useful resource for the advancement of progress toward hESC-based
      therapies in regenerative medicine.

PMID- 22472094
TI  - Partitioning of atmospheric carbon dioxide over Central Europe: insights from
      combined measurements of CO2 mixing ratios and their carbon isotope composition.
AB  - Regular measurements of atmospheric CO (2) mixing ratios and their carbon isotope
      composition ((13)C/(12)C and (14)C/(12)C ratios) performed between 2005 and 2009
      at two sites of contrasting characteristics (Krakow and the remote mountain site
      Kasprowy Wierch) located in southern Poland were used to derive fossil fuel
      related and biogenic contributions to the total CO (2) load measured at both
      sites. Carbon dioxide present in the atmosphere, not coming from fossil fuel and
      biogenic sources, was considered 'background' CO (2). In Krakow, the average
      contribution of fossil fuel CO (2) was approximately 3.4%. The biogenic component
      was of the same magnitude. Both components revealed a distinct seasonality, with
      the fossil fuel component reaching maximum values during winter months and the
      biogenic component shifted in phase by approximately 6 months. The partitioning
      of the local CO (2) budget for the Kasprowy Wierch site revealed large
      differences in the derived components: the fossil fuel component was
      approximately five times lower than that derived for Krakow, whereas the biogenic
      component was negative in summer, pointing to the importance of photosynthetic
      sink associated with extensive forests in the neighbourhood of the station. While
      the presented study has demonstrated the strength of combined measurements of CO
      (2) mixing ratios and their carbon isotope signature as efficient tools for
      elucidating the partitioning of local atmospheric CO (2) loads, it also showed
      the important role of the land cover and the presence of the soil in the
      footprint of the measurement location, which control the net biogenic surface CO
      (2) fluxes.

PMID- 22472095
TI  - Interpretation of the peak areas in gamma-ray spectra that have a large relative
      uncertainty.
AB  - Empirical evidence is provided that the areas of peaks having a relative
      uncertainty in excess of 30% are overestimated. This systematic influence is of a
      statistical nature and originates in way the peak-analyzing routine recognizes
      the small peaks. It is not easy to detect this influence since it is smaller than
      the peak-area uncertainty. However, the systematic influence can be revealed in
      repeated measurements under the same experimental conditions, e.g., in background
      measurements. To evaluate the systematic influence, background measurements were
      analyzed with the peak-analyzing procedure described by Korun et al. (2008). The
      magnitude of the influence depends on the relative uncertainty of the peak area
      and may amount, in the conditions used in the peak analysis, to a factor of 5 at
      relative uncertainties exceeding 60%. From the measurements, the probability for
      type-II errors, as a function of the relative uncertainty of the peak area, was
      extracted. This probability is near zero below an uncertainty of 30% and rises to
      90% at uncertainties exceeding 50%.

PMID- 22472096
TI  - Bioindication of volatile elements emission by the Puyehue-Cordon Caulle (North
      Patagonia) volcanic event in 2011.
AB  - The emission of volatile pollutants from the volcanic eruption of the Puyehue
      Cordon Caulle complex (North Patagonia Andean Range) that started in June 4th,
      2011, was investigated by bioindication means with the epyphytic fruticose lichen
      Usnea sp. The elemental composition of pooled samples made up with 10 lichen
      thalli were analysed by Instrumental Neutron Activation Analysis. Eleven sampling
      sites were selected within the impacted region at different distance from the
      volcanic source. Five sites were selected as they were already sampled in a
      previous study prior to the eruption. Two other new sampling sites were selected
      from outside the impacted zone to provide non-impacted baseline sites. The
      elements associated with the lichen incorporation of particulate matter (PM) of
      geological origin were identified by linear correlation with a geochemical tracer
      (Sm concentrations). The elements associated with PM uptake were Ce, Eu, Fe, Hf,
      La, Lu, Na, Nd, Sb, Sc, Se, Ta, Tb, Th, U, and Yb. Arsenic and Cs concentrations
      showed contributions exceeding the PM fraction in sites near the volcanic centre,
      also higher than the baseline concentrations, which could be associated with
      permanent emissions from the geothermal system of the Puyehue-Cordon Caulle
      complex. The lichen concentrations of Ba, Ca, Co, Hg, K, Rb, Sr, and Zn were not
      associated with the PM, not showing higher concentrations in the sites nearby the
      volcanic source or respect to the baseline values either. Therefore, there is no
      indication of the emission of volatile forms of these elements in the lichen
      records. The lichen records only identified Br volatile emissions associated with
      the Puyehue-Cordon Caulle complex eruption in 2011.

PMID- 22472097
TI  - Polychlorobiphenyls and organochlorine pesticides in conventional and organic
      brands of milk: occurrence and dietary intake in the population of the Canary
      Islands (Spain).
AB  - The population of the Spanish archipelago of the Canary Islands has been studied
      in depth regarding its levels of contamination by organochlorine pesticides (OCs)
      and polychlorinated biphenyls (PCBs). Foodstuffs of animal origin, such as milk,
      are prominent contributors to the body burden of these contaminants. As this
      population presents one of the highest milk-intake in Spain and Europe, we
      evaluated the level of OCs and PCBs in 26 commercially available brands of milk
      (16 conventional and 10 organic brands) present in the market of these Islands,
      in order to estimate the relevance of milk as a source of these chemicals for the
      Canary population. Our findings showed that hexachlorobenzene, trans-chlordane,
      and PCB153 were present in almost all the samples with independence of the type
      of milk. For both types of milks, the concentration of OCs was very low, showing
      organic milks lower levels than conventional ones. As a consequence, the
      estimated daily intake for OCs was lower than the tolerable daily intake (TDI)
      established by International Agencies. The levels of PCBs in milk were also found
      to be very low, but, in this case, the situation was the opposite: there were
      higher levels of PCBs in organic than in conventional brands of milk.
      Unexpectedly, levels of dioxin-like PCBs (DL-PCBs) reached values higher than 25
      pg WHO-TEQ g(-1) fat in percentile 75 for both types of milk indicating the
      existence of a number of brands of milk highly contaminated by these toxicants.
      Consequently, the population who consume the most contaminated milk brands could
      have estimated daily intakes well above the recommended TDI (2 pg WHO-TEQ kg(
      1)b.w.d(-1)) established by European Union Authorities. These results are of
      concern if we consider the well known adverse health effects exerted by dioxin
      like compounds.

PMID- 22472098
TI  - Evidence for in situ production of chlorinated polycyclic aromatic hydrocarbons
      on tidal flats: environmental monitoring and laboratory scale experiment.
AB  - This study investigated environmental distributions and production mechanisms of
      chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) in the sediments from some
      tidal flats located in Asia. Cl-PAHs were found in sediments taken from Arao
      tidal flat, Kikuchigawa River and Shirakawa River. The range of ?Cl-PAHs was from
      25.5 to 483 pg g(-1) for Kikuchigawa River and Arao tidal flat, respectively.
      Concentrations of PAHs and Cl-PAHs showed no significant correlations (r=0.134).
      This result suggests that the origins of these compounds differ. In the
      identified Cl-PAH isomers, the most abundant Cl-PAH isomer was 9,10
      dichloroanthracene (9,10-di-Cl-ANT) in the three sites. In general,
      concentrations of Cl-ANTs in the coastal environment are about 3-5 orders of
      magnitude lower than those of anthracene (ANT). However, concentration ratios
      between Cl-ANTs and ANT (Cl-ANTs/ANT) in the sediments ranged from 4.1% to 24.6%.
      This result indicated that Cl-PAHs were not generated under industrial processes
      but the high concentration ratios have resulted from the contribution of
      photochemical production of Cl-ANTs in the sediments because ANT is known to have
      high photochemical reactivity. For examining this phenomenon, ANT adsorbed onto
      glass beads was irradiated with UV under the mimicked field conditions of tidal
      flats. As a result, it was noticed that, while chlorinated derivatives were
      negligible in a light-controlled group, production of 2-Cl-ANT, 9-Cl-ANT and 9,10
      diCl-ANT on the irradiated surface were found in this study. These results
      suggest that photochemical reaction of PAHs can be a potential source of the
      occurrence of Cl-PAHs in the coastal environment.

PMID- 22472099
TI  - Application of phosphate-solubilizing bacteria for enhancing bioavailability and
      phytoextraction of cadmium (Cd) from polluted soil.
AB  - In this study, phosphate-solubilizing bacteria (PSB), Bacillus megaterium, were
      used to enhance Cd bioavailability and phytoextractability of Cd from
      contaminated soils. This strain showed a potential for directly solubilizing
      phosphorous from soils more than 10 folds greater than the control without
      inoculation. The results of pot experiments revealed that inoculation with B.
      megaterium significantly increased the extent of Cd accumulation in Brassica
      juncea and Abutilon theophrasti by two folds relative to the uninoculated
      control. The maximum Cd concentrations due to inoculation were 1.6 and 1.8 mg Cd
      g(-1) plant for B. juncea and A. theophrasti after 10 wk, respectively. The total
      biomass of A. theophrasti was not significantly promoted by the inoculation
      treatment, yet the total biomass of B. juncea increased from 0.087 to 0.448 g. It
      is also worth to mention that B. juncea predominantly accumulates Cd in its stems
      (39%) whereas A. theophrasti accumulates it in its leaves (68%) after 10 wk. The
      change of the Cd speciation indicated that inoculation of B. megaterium as PSB
      increased the bioavailabilty of Cd and consequently enhanced its uptake by
      plants. The present study may provide a new insight for improving
      phytoremediation using PSB in the Cd-contaminated soils.

PMID- 22472100
TI  - Mechanochemistry of ibuprofen pharmaceutical.
AB  - In this paper mechanochemistry has been studied in view of possible application
      to detoxification of expired pharmaceuticals. The experiments have been carried
      out with a commercial medication containing ibuprofen ((RS)-2-(4-(2
      methylpropyl)phenyl)propanoic acid) which has been submitted to prolonged milling
      up to 40h. When Al(OH)(3) is used as co-reagent, the first degradation step
      induced by the mechanochemical treatment is an acid-base reaction with the
      ibuprofen carboxylic acid group. The subsequent degradation follows a complex
      pathway leading to 1-(4-isobutylphenyl)ethanone, 1-isobutyl-4-vinylbenzene and 2
      (4-(3-methylbutan-2-yl)phenyl)propan-1-ol after 10h milling and, in addition, 1
      (4-acetylphenyl)-2-methylpropan-1-one, 1-(4-(1-hydroxy-2
      methylpropyl)phenyl)ethanone and 1-(4-(2-hydroxy-2-methylpropyl)phenyl)ethanone
      after 40h milling. The degradation reaction path and products have been
      identified by means of FT-IR spectroscopy, thin layer chromatography, NMR
      spectroscopy, mass spectroscopy and elemental analysis. The observed ibuprofen
      decarboxylation makes the drug simultaneously lose both its pharmaceutical
      activity and toxicity.

PMID- 22472101
TI  - Temporal trends (2005-2009) of PCDD/Fs, PCBs, PBDEs in rice hulls from an e-waste
      dismantling area after stricter environmental regulations.
AB  - Primitive e-waste dismantling activities have been of increasing concern due to
      serious environmental and human health problems, and therefore authorities in
      China have strengthened the regulations on illegal e-waste recycling activities.
      In this work, we used rice hull as a passive sampler and investigated temporal
      trends of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs),
      polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) in areas
      near e-waste recycling sites after the stricter regulations. Furthermore, the
      distribution patterns and composition profiles of these contaminants were also
      discussed. The average concentrations of the three groups of persistent organic
      pollutants (POPs) in rice hulls have markedly decreased during the period of 2005
      2009. Specifically, from 12.9 (average value in 2005) to 0.37 pg WHO-TEQ/g (dry
      weight, dw) (in 2009) for PCDD/Fs, 47.6 (2005) to 7.10 ng g(-1)dw (2009) for
      PCBs, and 2.51 (2005) to 0.89 ng g(-1), dw (2009) for PBDEs. The significant
      decrease of combustion markers 2,3,4,7,8-PeCDF, 1,2,3,6,7,8HxCDF and PCB126, and
      the PCDD/PCDF ratio from 1:9 (2005) to 7:3 (2009) is likely a result of stricter
      regulations on open combustion activities. This study suggests that stricter
      control measures, strengthened laws and regulations and more environmental
      friendly techniques could be effective measures in reducing the release and
      formation of related POPs in typical e-waste dismantling sites, and these
      measures could further improve the quality of the environment and health of the
      local inhabitants.

PMID- 22472102
TI  - Interference with xenobiotic metabolic activity by the commonly used vehicle
      solvents dimethylsulfoxide and methanol in zebrafish (Danio rerio) larvae but not
      Daphnia magna.
AB  - Organic solvents, such as dimethylsulfoxide (DMSO) and methanol are widely used
      as vehicles to solubilise lipophilic test compounds in toxicity testing. However,
      the effects of such solvents upon innate detoxification processes in aquatic
      organisms are poorly understood. This study assessed the effect of solvent
      exposure upon cytochrome P450 (CYP)-mediated xenobiotic metabolism in Daphnia
      magna and zebrafish larvae (4d post fertilisation). Adult D. magna were
      demonstrated to have a low, but detectable, metabolism of ethoxyresorufin in vivo
      and this activity was not modulated by pre-exposure to DMSO or methanol (24 h, up
      to 0.1% and 0.05% v/v, respectively). In contrast, the metabolism of
      ethoxyresorufin in zebrafish larvae was significantly reduced by both solvents
      (0.1% and 0.05% v/v, respectively) after 24 h of exposure. In zebrafish, these
      observed decreases in activity towards ethoxyresorufin were accompanied by
      decreased expression of a variety of genes coding for drug metabolising enzymes
      (corresponding to CYP1, CYP2, CYP3 and UDP-glucuronyl transferase [UGT] family
      enzymes), measured by quantitative PCR. Reduction of gene expression and CYP1
      enzyme activities by methanol (0.05% v/v) in zebrafish larvae was partially
      reversed by co-exposure with Aroclor 1254 (100 MUg L(-1)). Overall this study
      suggests that relatively low concentrations of organic solvents can impact upon
      the biotransformation of certain xenobiotics in zebrafish larvae, and that this
      warrants consideration when assessing compounds for metabolism and toxicity in
      this species.

PMID- 22472104
TI  - [Sickle-cell retinopathy: Retrospective study of 730 patients followed in a
      referral center].
AB  - INTRODUCTION: Sickle-cell disease is the most common genetic disease in the
      world, frequently complicated by potentially blinding retinal complications. The
      prevalence of sickle-cell retinopathy in patients followed in a referral center
      is presented in this study. PATIENTS AND METHODS: The prevalence of proliferative
      sickle-cell retinopathy by Goldberg classification was determined via a
      retrospective study of primarily adult SS and SC sickle-cell disease patients and
      AS sickle trait patients followed in a single referral center for a mean period
      of 13 years. All patients underwent slit lamp examination and complete fundus
      examination. RESULTS: Seven hundred and thirty patients (mean age 32.5+/-10
      years), consisting of 492 SS patients (67.4%), 229 SC patients (31.4%) and nine
      AS patients (1.2%), were included in the study. 54.6% of SC patients and 18.1% of
      SS patients had grade 3 to 5 proliferative sickle-cell retinopathy. The
      prevalence of severe forms of sickle-cell retinopathy was higher among SS men
      than among SS women (21.7% versus 15.5% ; P<0.05). CONCLUSION: The high
      prevalence of sickle-cell retinopathy and the potentially severe complications
      associated with this disease justify screening and therapeutic management by a
      multidisciplinary team in the setting of a referral center.

PMID- 22472103
TI  - Deep sequencing the circadian and diurnal transcriptome of Drosophila brain.
AB  - Eukaryotic circadian clocks include transcriptional/translational feedback loops
      that drive 24-h rhythms of transcription. These transcriptional rhythms underlie
      oscillations of protein abundance, thereby mediating circadian rhythms of
      behavior, physiology, and metabolism. Numerous studies over the last decade have
      used microarrays to profile circadian transcriptional rhythms in various
      organisms and tissues. Here we use RNA sequencing (RNA-seq) to profile the
      circadian transcriptome of Drosophila melanogaster brain from wild-type and
      period-null clock-defective animals. We identify several hundred transcripts
      whose abundance oscillates with 24-h periods in either constant darkness or 12 h
      light/dark diurnal cycles, including several noncoding RNAs (ncRNAs) that were
      not identified in previous microarray studies. Of particular interest are U
      snoRNA host genes (Uhgs), a family of diurnal cycling noncoding RNAs that encode
      the precursors of more than 50 box-C/D small nucleolar RNAs, key regulators of
      ribosomal biogenesis. Transcriptional profiling at the level of individual exons
      reveals alternative splice isoforms for many genes whose relative abundances are
      regulated by either period or circadian time, although the effect of circadian
      time is muted in comparison to that of period. Interestingly, period loss of
      function significantly alters the frequency of RNA editing at several editing
      sites, suggesting an unexpected link between a key circadian gene and RNA
      editing. We also identify tens of thousands of novel splicing events beyond those
      previously annotated by the modENCODE Consortium, including several that affect
      key circadian genes. These studies demonstrate extensive circadian control of
      ncRNA expression, reveal the extent of clock control of alternative splicing and
      RNA editing, and provide a novel, genome-wide map of splicing in Drosophila
      brain.

PMID- 22472105
TI  - Anti-diabetic activity of extract from Persea americana Mill. leaf via the
      activation of protein kinase B (PKB/Akt) in streptozotocin-induced diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Persea americana Mill. (Lauraceae)
      have been popularly used in the treatment of diabetes in countries in Latin
      America and Africa. AIM OF THE STUDY: To investigate the hypoglycaemic properties
      and to determine the molecular mechanism by which the hydroalcoholic extract of
      the leaves of Persea americana reduce blood glucose levels in streptozotocin
      (STZ)-induced diabetes in rats via the enzymatic pathway of protein kinase B
      (PKB/Akt). METHODS: The hydroalcoholic extract of the leaves of Persea americana
      (0.15 and 0.3g/kg/day), vehicle and metformin (0.5g/kg/day) were administered
      orally to STZ-diabetic rats (n=7/group) for 4 weeks. Changes in body weight, food
      and water intake, fasting glucose levels and oral glucose tolerance were
      evaluated. Phosphorylation and the expression of PKB in the liver and soleus
      muscle were determined by Western blot. RESULTS: The hydroalcoholic extract of
      the leaves of Persea americana reduced blood glucose levels and improved the
      metabolic state of the animals. Additionally, PKB activation was observed in the
      liver and skeletal muscle of treated rats when compared with untreated rats.
      CONCLUSION: The results indicate that the hydroalcoholic extract of the leaves of
      Persea americana has anti-diabetic properties and possibly acts to regulate
      glucose uptake in liver and muscles by way of PKB/Akt activation, restoring the
      intracellular energy balance.

PMID- 22472106
TI  - Involvement of 5-HT1A in the anxiolytic-like effect of dichloromethane fraction
      of Pimenta pseudocaryophyllus.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal applications of Pimenta
      pseudocaryophyllus infusion as a diuretic and aphrodisiac agent as well as
      tranquilizer in the form of tea for the treatment of emotional tension in
      Brazilian folk medicine has been in practice since time immemorial. Despite its
      popular therapeutic acceptance and claims, there are scanty scientific reports to
      corroborate its central biological activities. AIM: To characterize anxiolytic
      like effect of the dichloromethane fraction (DF) obtained from ethanolic leaf
      extract of the Pimenta pseudocaryophyllus and identify mechanisms of action
      involved while seeking to support its popular use as a soothing agent. MATERIAL
      AND METHODS: Mice (25-35 g) were treated orally with DF obtained from ethanolic
      leaf extract of Pimenta pseudocaryophyllus and were submitted to light-dark box
      (LDB) and elevated plus maze (EPM) tests. Different groups of mice were treated
      with flumazenil and NAN-190 to identify mechanisms of action involved in the
      anxiolytic-like effect of DF. RESULTS: Treatment with DF increased number of
      transitions and time spent in the light compartment of the LDB while the time
      spent and numbers of entries in the open arm of the LCE were significantly
      increased. Pre-treatment of the animal with flumazenil (2 mg/kg, i.p.-
      competitive antagonist of benzodiazepine site of GABA(A) receptor) did not block
      this effect, thereby excluding participation of benzodiazepine site of the
      GABA(A) receptor. However, anxiolytic-like effect of DF was reversed by pre
      treatment with NAN-190 (0.5 mg/kg, i.p.--an antagonist of the 5-HT(1A) receptor)
      thereby suggesting involvement of 5-HT(1A) receptor. The thin layer
      chromatography and high-performance liquid chromatography analysis indicated the
      predominance of (E)-methyl isoeugenol and oleanolic acid in DF. CONCLUSION: These
      results support the popular use of Pimenta pseudocaryophyllus as a calming agent
      and suggest the involvement of 5-HT(1A) receptor.

PMID- 22472107
TI  - Ginger (Zingiber officinale Roscoe) prevents the development of morphine
      analgesic tolerance and physical dependence in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginger (Zingiber officinale Roscoe), a well-known
      spice plant, has been used traditionally in the treatment of a wide variety of
      ailments such as opiates withdrawal-induced disorders. However, its influences on
      opioid tolerance and dependence have not yet been clarified. MATERIALS AND
      METHODS: Adult male Wistar rats were rendered tolerant to analgesic effect of
      morphine by injection of morphine (10 mg/kg, i.p.) twice daily for 8 days. To
      develop morphine dependence, rats given escalating doses of chronic morphine. To
      determine the effect of ginger on the development of morphine tolerance and
      dependence, different doses of ginger were administrated before morphine. The
      tail-flick and naloxone precipitation tests were used to assess the degree of
      tolerance and dependence, respectively. RESULTS: Our results showed that chronic
      morphine-injected rats displayed tolerance to the analgesic effect of morphine as
      well as morphine dependence. Ginger (50 and 100 mg/kg) completely prevented the
      development of morphine tolerance. In addition, concomitant treatment of morphine
      with 100 and 150 mg/kg attenuated almost all of the naloxone-induced withdrawal
      sings which include weight lose, abdominal contraction, diarrhea, petosis, teeth
      chattering, and jumping. In addition, morphine-induced L-type calcium channel
      over-expression in spinal cord was reversed by 100 mg/kg ginger. CONCLUSION: The
      data indicate that ginger extract has a potential anti-tolerant/anti-dependence
      property against chronic usage of morphine.

PMID- 22472108
TI  - Vasorelaxant action of the total alkaloid fraction obtained from Solanum
      paludosum Moric. (Solanaceae) involves NO/cGMP/PKG pathway and potassium
      channels.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Solanum paludosum Moric. (jurubeba-roxa) is
      commonly used to treat hypertension as a substitute for Solanum paniculatum L.
      (jurubeba verdadeira). The total ethanolic extract from the root bark of Solanum
      paludosum have been found to cause hypotension in rats. AIM OF THE STUDY: To
      investigate the mechanism by which the total alkaloid fraction obtained from the
      root bark of Solanum paludosum (FAT-SP) acts as a vasorelaxant agent on rat
      thoracic aorta. MATERIALS AND METHODS: Rings of rat aorta were suspended in organ
      bath containing Krebs solution at 37 degrees C, bubbled with carbogen mixture
      (95% O(2) and 5% CO(2)) under a resting tension of 1 g. Isometric contractions
      were measured using a force transducer coupled to an amplifier and a
      microcomputer. RESULTS: FAT-SP has been found cause relaxation of the aortic
      rings pre-contracted with phenylephrine (Phe) in a concentration-dependent
      manner, in the presence and absence of endothelium. This effect was more potent
      on the endothelium-intact aorta. In the presence of endothelium, neither
      indomethacin (non-selective cyclooxygenase inhibitor) nor atropine (non-selective
      muscarinic receptor antagonist), produced significant changes on the relaxation
      response. On the other hand, in the presence of calmidazolium (a calmodulin
      inhibitor), N-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase
      inhibitor), hydroxocobalamin (HDX) (scavenger of free-radical nitric oxide), 1-H
      [1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, selective blocker of soluble
      guanylate cyclase), Rp-8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3':5'-cyclic
      monophosphorothioate sodium salt hydrate (Rp-8-Br-PET-cGMPS, competitive
      inhibitor of cGMP-dependent protein kinase G) or TEA(+) (tetraethylammonium,
      nonselective potassium channel blocker), the vasorelaxant effect was
      significantly reduced, suggesting the involvement of NO/sCG/PKG pathway and
      potassium channel opening in vasorelaxant action of the FAT-SP. CONCLUSION: The
      mechanism of vasorelaxant activity of the FAT-SP on rat aorta involves both
      NO/sCG/PKG pathway and potassium channels.

PMID- 22472109
TI  - Immunomodulatory active compounds from Tinospora cordifolia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia mentioned as "Rasayana" is
      extensively used in various herbal preparations for the treatment of different
      ailments for its general tonic, antiperiodic, antispasmodic, antiinflammatory,
      antiarthritic, antiallergic and antidiabetic properties. It is extensively used
      in Ayurveda due to its potential in improving the immune system and the body
      resistance against infections. AIM OF THE STUDY: The aim of the study was to
      isolate and characterise the immunomodulatory active compounds of Tinospora
      cordifolia. MATERIALS AND METHODS: The immunomodulatory activity of different
      extracts, fractions and isolated compounds in relation to phagocytosis and
      reactive oxygen species production in human neutrophil cells have been
      investigated using the PMN phagocytic function studies, NBT, NO and
      chemiluminescence assay. RESULTS: The results obtained indicate that ethyl
      acetate, water fractions and hot water extract exhibited significant
      immunomodulatory activity with an increase in percentage phagocyctosis.
      Chromatographic purification of these fraction led to the isolation of a mixture
      of two compounds 2, 3 isolated for the first time from natural source and five
      known compounds 1, 4-7 which were characterized as 11-hydroxymustakone (2), N
      methyl-2-pyrrolidone (3), N-formylannonain (1), cordifolioside A (4),
      magnoflorine (5), tinocordiside (6), syringin (7) by nuclear magnetic resonance
      (NMR) and mass spectrometry (MS) and comparing the spectral data with reported
      one. Cordifolioside A and syringin have been reported to possess immunomodulatory
      activity. Other five compounds showed significant enhancement in phagocytic
      activity and increase in nitric oxide and reactive oxygen species generation at
      concentration 0.1-2.5 MUg/ml. CONCLUSIONS: Seven immunomodulatory active
      compounds belonging to different classes have been isolated and characterised
      indicating that the immunomodulatory activity of Tinospora cordifolia may be
      attributed to the synergistic effect of group of compounds.

PMID- 22472110
TI  - Anticancer potential of aqueous extract of alocasia macrorrhiza against hepatic
      cancer in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Alocasia macrorrhiza has been used as a folk
      medicine for cancer treatment in the Southwest of China. AIM OF THE STUDY: The
      purpose of this study is to confirm the anticancer activity of aqueous extract of
      alocasia macrorrhiza against hepatic cancer and to elucidate its mechanism of
      action. MATERIALS AND METHODS: Human normal liver cells and hepatocellular
      carcinoma cells were tested in vitro for cytotoxicity, colony formation
      inhibition, EdU incorporation, AO/EB staining apoptotic cells, apoptotic DNA
      fragmentation, and cell cycle distribution in response to alocasia macrorrhiza
      extract. The mRNA and protein expressions of PPARgamma, Cyclin D1, Rb, P21, Bax,
      Bcl-2 and caspase-3 were detected through RT-PCR and Western blotting; the tumor
      growth inhibition in vivo was tested by oral administration of the extract.
      RESULTS: Alocasia macrorrhiza aqueous extract exhibited proliferation inhibition
      and apoptosis effects on human hepatocellular carcinoma cells in vitro, inhibited
      hepatoma growth in vivo. CONCLUSION: Alocasia macrorrhiza extract has potential
      cytotoxic and apoptotic effect on human hepatocellular carcinoma cells and
      inhibits hepatoma growth in vivo, its mechanism of action might be associated
      with the inhibition of DNA synthesis, cell cycle (G(0)/G(1)) arrest, apoptosis
      induction through up-regulation the mRNA and protein expressions of PPARgamma,
      Rb, Bax and capase-3genes and down-regulation of the expressions of Cyclin D1 and
      Bcl-2 genes.

PMID- 22472111
TI  - Korean red ginseng and its primary ginsenosides inhibit ethanol-induced oxidative
      injury by suppression of the MAPK pathway in TIB-73 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (P. ginseng) is one of the most
      widely used medicinal plants due to its wide spectrum of medicinal effects. Among
      the currently available Panax ginseng products, Korea red ginseng (KRG) has been
      shown to exhibit a variety of antioxidative and hepatoprotective action. AIM OF
      THE STUDY: Our aim was to investigate the effects of KRG and its primary
      ginsenosides (Rg3 and Rh2) on EtOH-induced injury to mouse hepatocytes (TIB-73).
      MATERIALS AND METHODS: We investigated the effects of KRG and its primary
      ginsenoside on EtOH-induced injury to TIB-73 cells and evaluated MAPKs signals as
      a possible mechanism of action. Hepatocytic injury was evaluated by biochemical
      assays as cell viability, lactate dehydrogenase (LDH), aspartate aminotransferase
      (AST), ROS and mitochondria membrane potential (MMP) level in TIB-73 cells. The
      levels of MAPK activation were analyzed by Western blots. RESULTS: The results
      showed that exposure of EtOH to TIB-73 cells led to cell death and membrane
      damage, accompanied by a decrease in cell viability, MMP, and Mg(2+)
      concentrations, but an increase in LDH, AST, ROS and MAPK activation. KRG and its
      primary ginsenosides reduced EtOH-induced generation of ROS and the activation of
      ERK and JNK, and increased Mg(2+) concentrations. CONCLUSION: These results
      suggest that KRG and its primary ginsenosides inhibit EtOH-induced oxidative
      injury by suppression of the MAPK pathway in TIB-73 cells.

PMID- 22472112
TI  - Neuroprotective effects of tongluojiunao in neurons exposed to oxygen and glucose
      deprivation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tongluojiunao (TLJN) is an herb extract that
      mainly contains ginsenoside Rg1 and geniposide, which are clinically used for
      treating ischemic damages in the brain. AIM OF THE STUDY: In the stroke, cerebral
      ischemia followed by oxygen reperfusion induced apoptosis in hippocampal neurons,
      while extension of axons and dendrites in neurons may compensate for and repair
      damages of neuronal network in the hypoxia brain. In this study, we investigated
      whether TLJN can protect neurons against damages by ischemia in brain
      vasculature. MATERIALS AND METHODS: We measured cell viability and lactate
      dehydrogenase (LDH) release from primary culture of rat hippocampal neurons
      before and after the neurons were deprived of oxygen and glucose (OGD). In
      addition, the effects were evaluated with cell viability and neurite outgrowth
      before or after OGD. RESULTS: We found that TLJN could play a neuroprotective
      role to cultured primary rat hippocampal neurons under both normal and
      oxygen/glucose-deprivation (OGD) conditions. TLJN could protect both cultured
      primary rat hippocampal neurons and brain microvascular endothelial cells (BMECs)
      from cell death under both normal and oxygen/glucose-deprivation (OGD)
      conditions. Moreover, under the same conditions, BMECs-conditioned media
      pretreated by TNJN could also promote neuron viability and neurite outgrowth,
      indicating that TLJN stimulated BMECs to secret some neuroprotective/neurotrophic
      factors. CONCLUSION: These findings suggest that TLJN has a marked
      neuroprotective and neurotrophic roles by either direct or indirect operation,
      and provide insight into the mechanism of clinical efficacy of this drug against
      stroke.

PMID- 22472113
TI  - A comparison on the metabolic profiling of the Mexican anxiolytic and sedative
      plant Galphimia glauca four years later.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Galphimia glauca has a long traditional use, and
      continues to be used in Mexico as a natural tranquilizer for the treatment of
      Central Nervous System disorders as well as for other illnesses. AIM OF THE
      STUDY: In 2005 the initial use of metabolic profiling to populations of Galphimia
      glauca resulted in two of the six collected populations being producers for
      galphimines, the markers for sedative and anxiolytic activities. The aim of this
      investigation was to confirm the previously established metabolic profile, as
      well as the previous in vivo results on mice. Additionally in this study we
      wanted to investigate potential anti-inflammatory properties. MATERIALS AND
      METHODS: Four years later, we collected samples in the five localities designated
      for the first-stage investigation in 2005, and in two new locations. Metabolic
      profiling was carried out by means of (1)H NMR spectroscopy and multivariate data
      analysis applied to crude extracts from wild plant specimens. HPLC analysis was
      performed to confirm and quantify the presence of galphimines. Two
      neuropharmacological in vivo assays on mice were employed to study anxiolytic
      (elevated plus maze test) and sedative (sodium pentobarbital-induced hypnosis
      model) activities in the extracts. Anti-inflammatory activity was determined by
      using the tetradecanoylphorbol acetate-induced mouse ear inflammation model
      (TPA). RESULTS AND CONCLUSIONS: The results for the 2009 collected species were
      similar to the 2005 collection, confirming the metabolic profiles and that
      galphimines are consistent good markers for CNS activity. Galloylquinic acid
      levels varied between the years without, as of yet, known effects. In vivo anti
      inflammatory activity was similar for all plants and thus not linked with
      galphimines, requiring further studies to identify the active compound(s). Areas
      of collection affect neuropharmacological activities but not anti-inflammatory
      action.

PMID- 22472114
TI  - Is cognitive aging predicted by educational level?
AB  - A higher educational level has consistently been associated with a lower
      incidence of dementia. However, in the current issue of the Journal, Glymour et
      al. (Am J Epidemiol. 2012;175(8):750-759.) present findings that are in agreement
      with other research in showing a lack of association between educational level
      and cognitive decline in the elderly. These findings are not inconsistent with
      the hope, yet unproven, that persons might reduce their risk of dementia by
      engaging in cognitively stimulating activities.

PMID- 22472116
TI  - Is cognitive aging predicted by one's own or one's parents' educational level?
      results from the three-city study.
AB  - The authors examined the associations of participants' and their parents'
      educational levels with cognitive decline while addressing methodological
      limitations that might explain inconsistent results in prior work. Residents of
      Dijon, France (n = 4,480) 65 years of age or older who were enrolled between 1999
      and 2001 were assessed using the Isaacs' verbal fluency test, Benton Visual
      Retention Test, Trail Making Test B, and Mini-Mental State Examination up to 5
      times over 9 years. The authors used random-intercepts mixed models with inverse
      probability weighting to account for differential survival (conditional on past
      performance) and quantile regressions to assess bias from measurement floors or
      ceilings. Higher parental educational levels predicted better average baseline
      performances for all tests but a faster average decline in score on the Isaacs'
      test. Higher participant educational attainment predicted better baseline
      performances on all tests and slower average declines in Benton Visual Retention
      Test, Trail Making Test B, and Mini-Mental State Examination scores. Slope
      differences were generally small, and most were not robust to alternative model
      specifications. Quantile regressions suggested that ceiling effects might have
      modestly biased effect estimates, although the direction of this bias might
      depend on the test instrument. These findings suggest that the possible impacts
      of educational experiences on cognitive change are small, domain-specific, and
      potentially incorrectly estimated in conventional analyses because of measurement
      ceilings.

PMID- 22472117
TI  - Reducing violence by transforming neighborhoods: a natural experiment in
      Medellin, Colombia.
AB  - Neighborhood-level interventions provide an opportunity to better understand the
      impact that neighborhoods have on health. In 2004, municipal authorities in
      Medellin, Colombia, built a public transit system to connect isolated low-income
      neighborhoods to the city's urban center. Transit-oriented development was
      accompanied by municipal investment in neighborhood infrastructure. In this
      study, the authors examined the effects of this exogenous change in the built
      environment on violence. Neighborhood conditions and violence were assessed in
      intervention neighborhoods (n = 25) and comparable control neighborhoods (n = 23)
      before (2003) and after (2008) completion of the transit project, using a
      longitudinal sample of 466 residents and homicide records from the Office of the
      Public Prosecutor. Baseline differences between these groups were of the same
      magnitude as random assignment of neighborhoods would have generated, and
      differences that remained after propensity score matching closely resembled
      imbalances produced by paired randomization. Permutation tests were used to
      estimate differential change in the outcomes of interest in intervention
      neighborhoods versus control neighborhoods. The decline in the homicide rate was
      66% greater in intervention neighborhoods than in control neighborhoods (rate
      ratio = 0.33, 95% confidence interval: 0.18, 0.61), and resident reports of
      violence decreased 75% more in intervention neighborhoods (odds ratio = 0.25, 95%
      confidence interval 0.11, 0.67). These results show that interventions in
      neighborhood physical infrastructure can reduce violence.

PMID- 22472118
TI  - Children's perceptions of their cerebral palsy and their impact on life
      satisfaction.
AB  - PURPOSE: To assess an individual child's cognitive and emotional perceptions of
      their cerebral palsy (CP) and how these are associated with their reported life
      satisfaction and their functional walking ability. METHOD: Convenience sample of
      48 children with cerebral palsy, GMFCS (Gross Motor Function Classification
      System) I-IV, mean age of 12.2 +/- 2.5 years was recruited from tertiary level
      out-patient clinics. All children completed the Brief Illness Perception
      Questionnaire-Cerebral Palsy version (BIPQ-CP), Students' Life Satisfaction Scale
      (SLSS) and 1- and 6-min walk tests. RESULTS: Children with CP reported levels of
      global life satisfaction (mean score 31.4/42) equivalent to previous studies of
      typically developing children. Higher total SLSS scores were associated with
      lower concern about CP (rho = -0.61, p < 0.001), lower emotional impact (rho = 
      0.58, p < 0.001), fewer perceived consequences (rho = -0.53, p < 0.001) and
      perceptions of higher levels of personal control (rho = 0.40, p = 0.01). Multiple
      regression models using BIPQ-CP constructs found that a combination of lower
      level of concern and fewer perceived consequences predicted 46% of the variance
      in SLSS score (p < 0.001). GMFCS levels, walk distance and age were not
      significant predictors of life satisfaction. CONCLUSIONS: Life satisfaction in
      this group of children was strongly associated with a child's perceptions of
      their CP but was not associated with functional walking ability. Although the
      cross-sectional nature of the study precludes assumptions of causality,
      understanding children's cognitive and emotional beliefs about their cerebral
      palsy would seem to be an important adjunct to clinical management.

PMID- 22472119
TI  - CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that
      regulates breast cancer stem cells.
AB  - Cancer stem cells (CSC) play critical roles in cancer initiation, progression,
      and therapeutic refractoriness. Although many studies have focused on the genes
      and pathways involved in stemness, characterization of the factors in the tumor
      microenvironment that regulate CSCs is lacking. In this study, we investigated
      the effects of stromal fibroblasts on breast cancer stem cells. We found that
      compared with normal fibroblasts, primary cancer-associated fibroblasts (CAF) and
      fibroblasts activated by cocultured breast cancer cells produce higher levels of
      chemokine (C-C motif) ligand 2 (CCL2), which stimulates the stem cell-specific,
      sphere-forming phenotype in breast cancer cells and CSC self-renewal. Increased
      CCL2 expression in activated fibroblasts required STAT3 activation by diverse
      breast cancer-secreted cytokines, and in turn, induced NOTCH1 expression and the
      CSC features in breast cancer cells, constituting a cancer-stroma-cancer
      signaling circuit. In a xenograft model of paired fibroblasts and breast cancer
      tumor cells, loss of CCL2 significantly inhibited tumorigenesis and NOTCH1
      expression. In addition, upregulation of both NOTCH1 and CCL2 was associated with
      poor differentiation in primary breast cancers, further supporting the
      observation that NOTCH1 is regulated by CCL2. Our findings therefore suggest that
      CCL2 represents a potential therapeutic target that can block the cancer-host
      communication that prompts CSC-mediated disease progression.

PMID- 22472120
TI  - Loss of the ceramide transfer protein augments EGF receptor signaling in breast
      cancer.
AB  - Triple-negative breast cancers (TNBC) are especially refractory to treatment due
      to their negative hormone receptor and ErbB2/HER2 status. Therefore, the
      identification of cancer-associated deregulated signaling pathways is necessary
      to develop improved targeted therapies. Here, we show that expression of the
      ceramide transfer protein CERT is reduced in TNBCs. CERT transfers ceramide from
      the endoplasmic reticulum to the Golgi complex for conversion into sphingomyelin
      (SM). We provide evidence that by regulating cellular SM levels, CERT determines
      the signaling output of the EGF receptor (EGFR/ErbB1), which is upregulated in
      approximately 70% of TNBCs. CERT downregulation in breast cancer cells enhanced
      ErbB1 lateral mobility, ligand-induced autophosphorylation, internalization, and
      chemotaxis. Together, our findings provide a link between lipid metabolism at the
      Golgi with signaling at the plasma membrane, thereby implicating CERT loss in the
      progression of TNBCs.

PMID- 22472121
TI  - Histone deacetylase inhibitors influence chemotherapy transport by modulating
      expression and trafficking of a common polymorphic variant of the ABCG2 efflux
      transporter.
AB  - Histone deacetylase inhibitors (HDI) have exhibited some efficacy in clinical
      trials, but it is clear that their most effective applications have yet to be
      fully determined. In this study, we show that HDIs influence the expression of a
      common polymorphic variant of the chemotherapy drug efflux transporter ABCG2,
      which contributes to normal tissue protection. As one of the most frequent
      variants in human ABCG2, the polymorphism Q141K impairs expression, localization,
      and function, thereby reducing drug clearance and increasing chemotherapy
      toxicity. Mechanistic investigations revealed that the ABCG2 Q141K variant was
      fully processed but retained in the aggresome, a perinuclear structure, where
      misfolded proteins aggregate. In screening for compounds that could correct its
      expression, localization, and function, we found that the microtubule-disrupting
      agent colchicine could induce relocalization of the variant from the aggresome to
      the cell surface. More strikingly, we found that HDIs could produce a similar
      effect but also restore protein expression to wild-type levels, yielding a
      restoration of ABCG2-mediated specific drug efflux activity. Notably, HDIs did
      not modify aggresome structures but instead rescued newly synthesized protein and
      prevented aggresome targeting, suggesting that HDIs disturbed trafficking along
      microtubules by eliciting changes in motor protein expression. Together, these
      results showed how HDIs are able to restore wild-type functions of the common
      Q141K polymorphic isoform of ABCG2. More broadly, our findings expand the
      potential uses of HDIs in the clinic.

PMID- 22472123
TI  - Pedigree analysis of Czech Holstein calves with schistosoma reflexum.
AB  - BACKGROUND: Schistosoma reflexum (SR) is congenital syndrome briefly
      characterized by visceral eventration, severe dorsoflexion and ankylosis of the
      spine and arthrogryposis. A genetic etiology has been proposed, but conclusive
      evidence has not yet been provided. METHODS: Pedigree analysis was carried out in
      29 cases of SR in Czech Holsteins and Holstein crosses. Genetic relationship was
      evaluated and inbreeding coefficients calculated. Pedigrees of 15 Czech Holsteins
      fathering non-SR affected calves were used for comparison. RESULTS: Twenty-one
      cases occurred in one pedigree founded by three sires while three SR calves
      occurred in another pedigree with a common grandfather. The sex ratio between
      affected males and females was 11:6. Affected calves shared common ancestors
      different from those shared by the unaffected calves. The inbreeding coefficient
      in the SR affected calves was not increased compared to unaffected calves.
      CONCLUSIONS: The findings are consistent with SR being inherited autosomal
      recessively. Further studies are however needed to confirm this and therefore a
      breeding trial is recommended where a suspected heterozygous sire is mated to
      closely related females.

PMID- 22472122
TI  - Inhibiting systemic autophagy during interleukin 2 immunotherapy promotes long
      term tumor regression.
AB  - Administration of high-dose interleukin-2 (HDIL-2) has durable antitumor effects
      in 5% to 10% of patients with melanoma and renal cell carcinoma. However,
      treatment is often limited by side effects, including reversible, multiorgan
      dysfunction characterized by a cytokine-induced systemic autophagic syndrome.
      Here, we hypothesized that the autophagy inhibitor chloroquine would enhance IL-2
      immunotherapeutic efficacy and limit toxicity. In an advanced murine metastatic
      liver tumor model, IL-2 inhibited tumor growth in a dose-dependent fashion. These
      antitumor effects were significantly enhanced upon addition of chloroquine. The
      combination of IL-2 with chloroquine increased long-term survival, decreased
      toxicity associated with vascular leakage, and enhanced immune cell proliferation
      and infiltration in the liver and spleen. HDIL-2 alone increased serum levels of
      HMGB1, IFN-gamma, IL-6, and IL-18 and also induced autophagy within the liver and
      translocation of HMGB1 from the nucleus to the cytosol in hepatocytes, effects
      that were inhibited by combined administration with chloroquine. In tumor cells,
      chloroquine increased autophagic vacuoles and LC3-II levels inhibited oxidative
      phosphorylation and ATP production and promoted apoptosis, which was associated
      with increased Annexin-V(+)/propidium iodide (PI)(-) cells, cleaved PARP, cleaved
      caspase-3, and cytochrome c release from mitochondria. Taken together, our
      findings provide a novel clinical strategy to enhance the efficacy of HDIL-2
      immunotherapy for patients with cancer.

PMID- 22472124
TI  - Serum concentrations of phthalate metabolites are related to abdominal fat
      distribution two years later in elderly women.
AB  - BACKGROUND: Phthalates, commonly used to soften plastic goods, are known PPAR
      agonists affecting lipid metabolism and adipocytes in the experimental setting.
      We evaluated if circulating concentrations of phthalates were related to
      different indices of obesity using data from the Prospective Investigation of the
      Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray
      absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used.
      METHODS: 1,016 subjects aged 70 years were investigated in the PIVUS study. Four
      phthalate metabolites were detected in the serum of almost all subjects (> 96%)
      by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was
      performed in a representative subsample of 287 subjects (28%), and a dual-energy
      X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two
      year following the phthalate measurements. RESULTS: In women, circulating
      concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist
      circumference, total fat mass and trunk fat mass by DXA, as well as to
      subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and
      triglycerides, education, smoking and exercise habits (all p < 0.008). Mono
      methyl phthalate (MMP) concentrations were related to trunk fat mass and the
      trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such
      statistically significant relationships were seen in men. CONCLUSIONS: The
      present evaluation shows that especially the phthalate metabolite MiBP was
      related to increased fat amount in the subcutaneous abdominal region in women
      measured by DXA and MRI two years later.

PMID- 22472125
TI  - Extending the sufficient component cause model to describe the Stable Unit
      Treatment Value Assumption (SUTVA).
AB  - Causal inference requires an understanding of the conditions under which
      association equals causation. The exchangeability or no confounding assumption is
      well known and well understood as central to this task. More recently the
      epidemiologic literature has described additional assumptions related to the
      stability of causal effects. In this paper we extend the Sufficient Component
      Cause Model to represent one expression of this stability assumption--the Stable
      Unit Treatment Value Assumption. Approaching SUTVA from an SCC model helps
      clarify what SUTVA is and reinforces the connections between interaction and
      SUTVA.

PMID- 22472126
TI  - Single centre experience with pegylated interferon and ribavirin for hepatitis C:
      looking back before moving forward.
AB  - BACKGROUND: Hepatitis C treatment is successful in 40-80% of patients in drug
      sponsored registration trials. However, few studies have examined treatment
      outcomes in non-trial, routine clinical practice settings. AIM: The aim of this
      study was to investigate the treatment outcomes and predictors of a sustained
      virological response in a routine clinical setting. METHODS: Data were collected
      retrospectively on patients treated for hepatitis C between January 2004 and
      March 2010 in a tertiary hospital setting. Demographics, treatment outcomes and
      potential predictors of outcome (viral genotype, viral load, virological
      response, platelet count, alanine transaminase level, glucose, ferritin, weight,
      fibrosis and cirrhosis, compliance, dose reductions, adverse events, psychiatric
      and alcohol history) were recorded. Univariate and multiple logistic regressions
      were performed. RESULTS: A total of 405 patients was treated during the study
      period. On an intention to treat basis, sustained virological response rates were
      55%, 82% and 72% in genotypes 1, 2 and 3 respectively. Predictors of response
      were gender, age, genotype, weight, fibrosis, cirrhosis, platelet count and
      alanine transaminase on univariate analysis. Age, genotype, cirrhosis and
      platelet count were independently associated with sustained virological response
      on multiple logistic regression. CONCLUSION: In our cohort, treatment outcomes
      for genotype 1 and 2 were similar to results from clinical trials but results for
      genotype 3 were inferior. Clinicians should not assume that results from
      registration trials are transferable to their own clinical practice. This has
      particular relevance for the new era of triple therapy regimens containing direct
      antivirals.

PMID- 22472127
TI  - Health-related quality of life advantage of long-acting injectable antipsychotic
      treatment for schizophrenia: a time trade-off study.
AB  - BACKGROUND: This study was undertaken to estimate utility values for alternative
      treatment intervals for long acting antipsychotic intramuscular injections for
      the treatment of schizophrenia. METHODS: Vignettes were developed using the
      published literature and an iterative consultation process with expert clinicians
      and patient representative groups. Four vignettes were developed. The first was a
      vignette of relapsed/untreated schizophrenia. The other three vignettes presented
      a standardised picture of well-managed schizophrenia with variations in the
      intervals between injections: once every 2-weeks, 4-weeks and 3-months. A
      standardised time trade off (TTO) approach was used to obtain utility values for
      the vignettes. As a societal perspective was sought, a representative sample of
      individuals from across the community (Sydney, Australia) was recruited. Ninety
      eight people completed the TTO interview. The vignettes were presented in random
      order to prevent possible ordering effects. RESULTS: A clear pattern of
      increasing utility was observed with increasing time between injections.
      Untreated schizophrenia was rated as very poor health-related quality of life
      with a mean (median) utility of 0.27 (0.20). The treated health states were rated
      at much higher utilities and were statistically significantly different (p <
      0.001) from each other: (1) 2-weekly: mean (median) utility = 0.61 (0.65); (2) 4
      weekly: mean (median) utility = 0.65 (0.70); (3) 3-monthly: mean (median) utility
      = 0.70 (0.75). CONCLUSIONS: This study has provided robust data indicating that
      approximately a 0.05 utility difference exists between treatment options, with
      the highest utility assigned to 3-monthly injections.

PMID- 22472128
TI  - A comparative study of defibrillation and cardiopulmonary resuscitation
      performance during simulated cardiac arrest in nursing student teams.
AB  - BACKGROUND: Although nurses must be able to respond quickly and effectively to
      cardiac arrest, numerous studies have demonstrated poor performance. Simulation
      is a promising learning tool for resuscitation team training but there are few
      studies that examine simulation for training defibrillation and cardiopulmonary
      resuscitation (D-CPR) in teams from the nursing education perspective. The aim of
      this study was to investigate the extent to which nursing student teams follow
      the D-CPR-algorithm in a simulated cardiac arrest, and if observing a simulated
      cardiac arrest scenario and participating in the post simulation debriefing would
      improve team performance. METHODS: We studied video-recorded simulations of D-CPR
      performance in 28 nursing student teams. Besides describing the overall
      performance of D-CPR, we compared D-CPR performance in two groups. Group A (n =
      14) performed D-CPR in a simulated cardiac arrest scenario, while Group B (n =
      14) performed D-CPR after first observing performance of Group A and
      participating in the debriefing. We developed a D-CPR checklist to assess team
      performance. RESULTS: Overall there were large variations in how accurately the
      nursing student teams performed the specific parts of the D-CPR algorithm. While
      few teams performed opening the airways and examination of breathing correctly,
      all teams used a 30:2 compression: ventilation ratio.We found no difference
      between Group A and Group B in D-CPR performance, either in regard to total
      points on the check list or to time variables. CONCLUSION: We found that none of
      the nursing student teams achieved top scores on the D-CPR-checklist. Observing
      the training of other teams did not increase subsequent performance. We think all
      this indicates that more time must be assigned for repetitive practice and
      reflection. Moreover, the most important aspects of D-CPR, such as early
      defibrillation and hands-off time in relation to shock, must be highlighted in
      team-training of nursing students.

PMID- 22472129
TI  - Synthesis of hydroxyapatite nanoparticles by a novel ultrasonic assisted with
      mixed hollow sphere template method.
AB  - Hydroxyapatite (HAP) is the main inorganic component of bone material and is
      widely used in various biomedical applications due to its excellent bioactivity
      and biocompatibility. In this paper, we have reported the synthesis of
      hydroxyapatite nanoparticles by a novel ultrasonic assisted mixed template
      directed method. In this method glycine-acrylic acid (GLY-AA) hollow spheres were
      used as an organic template which could be prepared by mixing of glycine with
      acrylic acid. The as-synthesized HAP nanoparticles were characterized by X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning
      electron microscope (SEM) and tunnelling electron microscope (TEM) to investigate
      the nature of bonding, crystallinity, size and shape. The thermal stability of as
      synthesized nanoparticles was also investigated by the thermo gravimetric
      analysis (TGA). The effect of ultrasonic irradiation time on the crystallinity
      and size of the HAP nanoparticles in presence of glycine-acrylic acid hollow
      spheres template were investigated. From the inspection of the above results it
      is confirmed that the crystallinity and size of the HAP nanoparticles decrease
      with increasing ultrasonic irradiation time. Hence the proposed synthesis
      strategy provides a facile pathway to obtain nano sized HAP with high quality,
      suitable size and morphology.

PMID- 22472130
TI  - Phonon dispersion and heat capacity in polyfuran.
AB  - A study of the normal modes of vibration and their dispersion in polyfuran (Pfu)
      based on the Urey-Bradley force field is reported. It provides a detailed
      interpretation of IR and Raman spectra. Characteristic features of dispersion
      curves such as regions of high density-of-states, repulsion and character mixing
      of dispersive modes are discussed. Predictive values of heat capacity as a
      function of temperature are calculated.

PMID- 22472131
TI  - A vibrational spectroscopic study of the phosphate mineral Wardite
      NaAl3(PO4)2(OH)4.2(H2O).
AB  - Three wardite mineral samples from different origins have been analysed by
      vibrational spectroscopy. The mineral is unusual in that it belongs to a unique
      symmetry class, namely the tetragonal-trapezohedral group. The structure of
      wardite contains layers of corner-linked OH bridged MO(6) octahedra stacked along
      the tetragonal C-axis in a four-layer sequence and linked by PO(4) groups.
      Consequentially not all phosphate units are identical. Thus, two intense Raman
      bands observed at 995 and 1051 cm(-1) are assigned to the nu(1) PO(4)(3-)
      symmetric stretching mode. Intense Raman bands are observed at 605 and 618 cm(-1)
      with shoulders at 578 and 589 cm(-1) are assigned to the nu(4) out of plane
      bending modes of the PO(4)(3-). The observation of multiple bands supports the
      concept of non-equivalent phosphate units in the structure. Sharp infrared bands
      are observed at 3544 and 3611 cm(-1) are attributed to the OH stretching
      vibrations of the hydroxyl units. Vibrational spectroscopy enables subtle details
      of the molecular structure of wardite to be determined.

PMID- 22472132
TI  - A competitive chemiluminescence enzyme immunoassay for rapid and sensitive
      determination of enrofloxacin.
AB  - With alkaline phosphatase (ALP)-adamantane (AMPPD) system as the
      chemiluminescence (CL) detection system, a highly sensitive, specific and simple
      competitive chemiluminescence enzyme immunoassay (CLEIA) was developed for the
      measurement of enrofloxacin (ENR). The physicochemical parameters, such as the
      chemiluminescent assay mediums, the dilution buffer of ENR-McAb, the volume of
      dilution buffer, the monoclonal antibody concentration, the incubation time, and
      other relevant variables of the immunoassay have been optimized. Under the
      optimal conditions, the detection linear range of 350-1000 pg/mL and the
      detection limit of 0.24 ng/mL were provided by the proposed method. The relative
      standard deviations were less than 15% for both intra and inter-assay precision.
      This method has been successfully applied to determine ENR in spiked samples with
      the recovery of 103%-96%. It showed that CLEIA was a good potential method in the
      analysis of residues of veterinary drugs after treatment of related diseases.

PMID- 22472133
TI  - Effect of alpha- and beta-cyclodextrins on the intramolecular charge transfer and
      intramolecular proton transfer fluorescence of methyl o-hydroxy p
      dimethylaminobenzoate.
AB  - The influence of alpha- and beta-cyclodextrins on the spectral characteristics of
      methyl o-hydroxy p-dimethylaminobenzoate has been studied using steady-state and
      time-resolved spectroscopic technique. The stoichiometries and equilibrium
      constants of the solute molecule-cyclodextrin inclusion complexes have been
      determined by the steady-state fluorescence measurements. Nonlinear least-squares
      regression analysis indicates that both 1:1 and 1:2 inclusion complexes were
      formed between studied compound and alpha- and beta-cyclodextrins. The
      contribution of the fluorophore in free, 1:1, and 1:2 complexes was calculated
      for a particular concentration of alpha- and beta-CD. Additionally, the location
      of the fluorophore inside the cavity was reported, with regard to the intra- and
      intermolecular proton transfer and intramolecular charge transfer processes.

PMID- 22472134
TI  - Eight stereoisomers of homonojirimycin from D-mannose.
AB  - Although there are 32 6-azidoheptitols, there are only 16 homonojirimycin (HNJ)
      stereoisomers. Two epimeric azidoalditols derived from d-mannose allow the
      synthesis in water of eight stereoisomers of HNJ.

PMID- 22472135
TI  - SUITO index for evaluation of clinical islet transplantation.
AB  - The major endpoints for clinical islet transplantation for type 1 diabetes are
      insulin independence and reduction of hypoglycemic episodes. Both endpoints are
      influenced by patients' and physicians' preferences regarding the use of
      exogenous insulin. Therefore, development of an objective endpoint for assessing
      clinical islet transplantation is desirable. HOMA-beta score is useful in
      assessing functional beta-cell mass. However, this score uses blood insulin
      levels that are influenced by exogenous insulin injection and therefore is not
      suitable for patients who receive exogenous insulin. For assessing functional
      beta-cell mass for type 1 diabetic patients after islet transplantation, we
      created the Secretory Unit of Islet Transplant Objects (SUITO) index using
      fasting C-peptide and fasting glucose. The formula of the SUITO index is fasting
      C-peptide (ng/ml)/[fasting blood glucose - 63 (mg/dl)] * 1500. We demonstrated
      that, within 1 month of islet transplantation, an average SUITO index of >26 was
      an excellent predictor of achieving insulin independence. In addition, daily
      SUITO index scores correlated with a reduction of insulin dose and adversely
      correlated with blood glucose levels during an intravenous glucose tolerance
      test. Other important endpoints, reduction of hypoglycemic episodes and quality
      of life, also correlated with the SUITO index. Thus, the SUITO index is excellent
      for assessing important endpoints (insulin independence, reduction of
      hypoglycemia, improved quality of life) after allogeneic islet transplantation.

PMID- 22472136
TI  - Heavy metals content by ICP-OES in Sarda sarda, Sardinella aurita and Lepidopus
      caudatus from the Strait of Messina (Sicily, Italy).
AB  - In this study copper, nickel, lead, cadmium, arsenic, chromium and vanadium
      content was measured in the muscles and gills of 24 fishes (Sarda sarda,
      Sardinella aurita and Lepidopus caudatus) caught in the Strait of Messina, by
      inductively coupled plasma-optical emission spectroscopy with microwave digestion
      techniques. In general, it was found that arsenic was higher than other analytes
      in all fish species, particularly its content was much higher in S. aurita than
      in the other two exemplary species. Lead and cadmium were always detected with
      values below the legal limits (CE no. 1881/2006 and subsequent modification CE
      no. 629/2008).

PMID- 22472137
TI  - Vis Medicatrix naturae: does nature "minister to the mind"?
AB  - The healing power of nature, vis medicatrix naturae, has traditionally been
      defined as an internal healing response designed to restore health. Almost a
      century ago, famed biologist Sir John Arthur Thomson provided an additional
      interpretation of the word nature within the context of vis medicatrix, defining
      it instead as the natural, non-built external environment. He maintained that the
      healing power of nature is also that associated with mindful contact with the
      animate and inanimate natural portions of the outdoor environment. A century on,
      excessive screen-based media consumption, so-called screen time, may be a driving
      force in masking awareness of the potential benefits of nature. With global
      environmental concerns, rapid urban expansion, and mental health disorders at
      crisis levels, diminished nature contact may not be without consequence to the
      health of the individual and the planet itself. In the context of emerging
      research, we will re-examine Sir J. Arthur Thomson's contention that the healing
      power of the nature-based environment - green space, forests and parks in
      particular - extends into the realm of mental health and vitality.

PMID- 22472138
TI  - Uptake of conjugated linolenic acids and conversion to cis-9, trans-11-or trans
      9, trans-11-conjugated linoleic acids in Caco-2 cells.
AB  - Dietary oils containing large amounts of conjugated linolenic acids (CLnA) may be
      regarded as a source of conjugated linoleic acids (CLA), which have been
      suspected to bear health-promoting properties. Indeed, CLnA can be converted into
      CLA in mammals. The objective of the present study was to investigate the uptake
      of CLnA and their metabolism into CLA in Caco-2 cells, as a validated in vitro
      model of the intestinal barrier. Caco-2 cells were incubated for 24 h in the
      presence of either alpha-eleostearic, beta-eleostearic, catalpic or punicic acid.
      We first observed that Caco-2 cells take these CLnA up at different rates and
      then convert them but with varying efficiency depending on the structure of the
      Delta13 double bond. Finally, the distribution of CLnA between neutral lipids
      (NL) and phospholipids appeared to be linked to their number of trans double
      bonds: the higher the number, the higher the accumulation in the NL fraction.

PMID- 22472139
TI  - Disruption of redox homeostasis in cerebral cortex of developing rats by
      acylcarnitines accumulating in medium-chain acyl-CoA dehydrogenase deficiency.
AB  - Medium-chain fatty acids and acylcarnitines accumulate in medium-chain acyl-CoA
      dehydrogenase deficiency (MCADD), the most frequent fatty acid oxidation defect
      clinically characterized by episodic crises with vomiting, seizures and coma.
      Considering that the pathophysiology of the neurological symptoms observed in
      MCADD is poorly known and, to our knowledge, there is no report on the
      involvement of acylcarnitines in the brain damage presented by the affected
      patients, the objective of the present study was to investigate the in vitro
      effects of hexanoylcarnitine (HC), octanoylcarnitine, decanoylcarnitine (DC) and
      cis-4-decenoylcarnitine (cDC) at concentrations varying from 0.01 to 1.0mM on
      important oxidative stress parameters in cerebral cortex of young rats. HC, DC
      and cDC significantly induced lipid peroxidation, as determined by increased
      thiobarbituric acid-reactive substances (TBA-RS) values. In addition, carbonyl
      formation was significantly augmented and sulfhydryl content diminished by DC,
      reflecting induction of protein oxidative damage. HC, DC and cDC also decreased
      glutathione (GSH) levels, the most important brain antioxidant defense.
      Furthermore, DC-induced elevation of TBA-RS values and decrease of GSH levels
      were prevented by the free radical scavengers melatonin and alpha-tocopherol,
      indicating the involvement of reactive oxygen species in these effects. We also
      found that l-carnitine itself did not induce lipid and protein oxidative damage,
      neither reduced the antioxidant defenses. Our present data show that the major
      medium-chain acylcarnitines accumulating in MCADD elicit oxidative stress in rat
      brain. It is therefore presumed that these compounds may be involved to a certain
      extent in the pathogenesis of the neurologic dysfunction of MCADD.

PMID- 22472140
TI  - Comparisons of personal exposure to PM2.5 and CO by different commuting modes in
      Beijing, China.
AB  - BACKGROUND: Epidemiological studies have shown that commuting in traffic is
      associated with adverse health effects. It is vital to investigate commuters'
      exposure to traffic-related air pollutants before considering potential health
      risks. However, there are relatively few publications considering commuters'
      personal exposure in China. METHOD: We carried out a field investigation
      measuring commuters' personal exposure to particulate matter <=2.5 MUm in
      aerodynamic diameter (PM(2.5)) and carbon monoxide (CO) by three commuting modes
      in Beijing. Both PM(2.5) and CO personal concentrations and whole trip exposures
      were compared among the three commuting modes. RESULTS: After controlling
      confounding factors, we found that taxi commuters were exposed to lower
      concentrations of PM(2.5) (31.64+/-20.77 MUg/m(3)) compared with bus commuters
      (42.40+/-23.36 MUg/m(3)) and cyclists (49.10+/-26.60 MUg/m(3)). By contrast, CO
      personal concentrations were significantly higher when commuting by taxi (5.21+/
      1.52 ppm) than by bus (2.41+/-0.99 ppm) and bicycle (1.90+/-0.55 ppm). However,
      when inhalation rates and trip duration were taken into consideration, cyclists
      experienced the highest whole trip exposures to both PM(2.5) and CO (p<0.05). We
      also found fixed site monitoring data were not appropriate surrogates for
      personal exposure while commuting, especially during traffic heavy times.
      CONCLUSION: PM(2.5) and CO personal concentrations were greatly influenced by the
      commuting mode. Furthermore, the highest whole trip exposures to PM(2.5) and CO
      which cyclists experienced indicates it is not preferable to commute by bicycle
      in a relatively high air polluted environment. Cyclists are possibly subject to
      greater health risks than other commuters. Thus further research needs to be
      conducted to investigate the health risks associated with cycling.

PMID- 22472141
TI  - Knowledge mobilization in the context of health technology assessment: an
      exploratory case study.
AB  - BACKGROUND: Finding measures to enhance the dissemination and implementation of
      their recommendations has become part of most health technology assessment (HTA)
      bodies' preoccupations. The Quebec government HTA organization in Canada observed
      that some of its projects relied on innovative practices in knowledge production
      and dissemination. A research was commissioned in order to identify what
      characterized these practices and to establish whether they could be
      systematized. METHODS: An exploratory case study was conducted during summer and
      fall 2010 in the HTA agency in order to determine what made the specificity of
      its context, and to conceptualize an approach to knowledge production and
      dissemination that was adapted to the mandate and nature of this form of HTA
      organization. Six projects were selected. For each, the HTA report and
      complementary documents were analyzed, and semi-structured interviews were
      carried out. A narrative literature review of the most recent literature reviews
      of the principal knowledge into practice frameworks (2005-2010) and of articles
      describing such frameworks (2000-2010) was undertaken. RESULTS AND DISCUSSION:
      Our observations highlighted an inherent difficulty as regards applying the
      dominant knowledge translation models to HTA and clinical guidance practices. For
      the latter, the whole process starts with an evaluation question asked in a
      problematic situation for which an actionable answer is expected. The objective
      is to produce the evidence necessary to respond to the decision-maker's request.
      The practices we have analyzed revealed an approach to knowledge production and
      dissemination, which was multidimensional, organic, multidirectional, dynamic,
      and dependent on interactions with stakeholders. Thus, HTA could be considered as
      a knowledge mobilization process per se. CONCLUSIONS: HTA's purpose is to solve a
      problem by mobilizing the types of evidence required and the concerned actors, in
      order to support political, organizational or clinical decision-making. HTA
      relies on the mediation between contextual, colloquial and scientific evidence,
      as well as on interactions with stakeholders for recommendation making. Defining
      HTA as a knowledge mobilization process might contribute to consider the
      different orders of knowledge, the social, political and ethical dimensions, and
      the interactions with stakeholders, among the essential components required to
      respond to the preoccupations, needs and contexts of all actors concerned with
      the evaluation question's issues.

PMID- 22472142
TI  - Study of the photoinduced supramolecular chirality in columnar liquid crystals by
      infrared and VCD spectroscopies.
AB  - IR and VCD spectroscopies are employed to clarify the molecular origins of
      supramolecular chirality in azobenzene-containing columnar liquid crystals. The
      different columnar mesomorphic assemblies, Colr and Colh, of an achiral and a
      chiral propeller-like hydrogen-bonded complex, respectively, are used for this
      study. The mesomorphic behavior of the achiral complex is studied here for the
      first time, and the structural parameters of its Colr mesophase are determined by
      X-ray diffraction. Both complexes bear azobenzene units and this makes it
      possible to implement photoresponsive columnar architectures, the chirality of
      which can be induced and modulated by irradiation with 488 nm circularly
      polarized light (CPL). Thin films of the respective rectangular and hexagonal
      columnar phases of these complexes have been processed in order to study the IR
      absorption spectra and the vibrational circular dichroism responses upon
      irradiation with CPL. These studies allow confirming that the outer part of the
      columns, consisting on azobenzene groups, is mainly involved in the photoinduced
      supramolecular chirality, rather than the inner part of the columns where a
      melamine core is located. This supports a structural model based on the helical
      disposition of the azobenzene groups along the stacked propeller-like complexes. 

PMID- 22472143
TI  - Evaluation of an Australian chest pain assessment unit.
AB  - BACKGROUND: In order to mitigate the risk of missing atypical or low probability
      presentations of acute coronary syndromes (ACS), many hospitals have designated
      resources specifically for the assessment of chest pain. AIM: This study aims to
      evaluate the introduction of a chest pain assessment unit (CPAU) in a North
      Queensland hospital. METHODS: Information on admission status, diagnosis,
      procedures, length of stay and chest pain representation rates was obtained for
      patients presenting with chest pain to the emergency department (ED) at The
      Townsville Hospital in the 2.5 years prior to the introduction of a CPAU in March
      2007 (n = 6665). This was compared with information on chest pain patients (n =
      7885) presenting to the ED in the 2.5 years after it opened. RESULTS: The CPAU
      resulted in a reduction in the percentage of 'missed' cases of ACS. The rate of
      people who represented with chest pain at 3 months and who ultimately received an
      ACS diagnosis reduced from 1.9% to 1.4%. There was an increased rate of
      apparently appropriate angiograms from 6.7% to 9.4% of chest pain admissions. The
      admission rate of ED chest pain presentations was stable as was the median length
      of stay (1.14-1.16 days). A relative decrease in the proportion of admitted
      patients diagnosed with ACS compared with those with unspecified chest pain was
      observed. CONCLUSION: The implementation of a CPAU at The Townsville Hospital
      resulted in improved care of those presenting to the ED with chest pain. Further
      Australian CPAU evaluations are recommended.

PMID- 22472144
TI  - Discrepant findings of computed tomography quantification of minimal lumen area
      of coronary artery stenosis: correlation with intravascular ultrasound.
AB  - OBJECTIVES: To study the diagnostic performance of computed tomography (CT)
      quantification of minimal lumen area (MLA) based on multiple factors (image
      quality, calcification and lesion locations), with reference to intravascular
      ultrasound (IVUS). METHODS: Consecutive clinically ordered patients were
      prospectively enrolled in our study. CT quantification of MLA was manually
      measured on cross-sectional view and further compared with IVUS findings. A
      significant lesion was defined as <=6 mm2 MLA for the left main (LM) coronary
      artery and a <=4 mm2 MLA for other epicardial vessels. RESULTS: Non-calcified
      lesions had good correlation between CT and IVUS (r=0.96) and the sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      were 85% (51/60), 93.94% (31/33), 96.23% (51/53) and 77.5% (31/40) respectively.
      Decreased correlation (r=0.814) lower specificity (23.81% (5/21)) and positive
      predictive value (60.98% (25/41)) were observed in calcified subgroup. Artifact
      absent lesions demonstrated excellent correlation (r=0.967) and the sensitivity,
      specificity, PPV and NPV were 96% (48/50), 93.94% (31/33), 96% (48/50) and 93.94%
      (31/33) respectively. Impaired correlation (r=0.584) was noted in artifact
      present lesions and the sensitivity, specificity, PPV and NPV were 80% (28/35),
      23.81% (5/21), 63.64% (28/44) and 41.67% (5/12) respectively. Excellent
      correlation between CT and IVUS was noted in proximal epicardial vessels
      (r=0.908) and the sensitivity, specificity, PPV and NPV were 92.31% (36/39),
      78.13% (25/32), 83.72% (36/43) and 89.29% (25/28) respectively. Middle right
      coronary artery lesions showed non-significant correlation (r=0.54, p=0.055).
      CONCLUSIONS: CT quantification of MLA can only be accurately achieved in non
      calcified lesions with absence of artifact. Diagnostic performance is impaired in
      calcified lesions.

PMID- 22472145
TI  - Minimally invasive colorectal surgery.

PMID- 22472146
TI  - Spectrographic cry analysis in newborns with profound hearing loss and perinatal
      high-risk newborns.
AB  - BACKGROUND: Crying is the first neurophysiological demonstration of the newborn.
      The acoustic analysis of crying episodes can provide useful information in the
      early diagnosis of several pathologies. METHODS: We carried out a spectrographic
      cry analysis of 40 infants with several diseases such as neonatal asphyxia,
      breathing disorders, deafness and neurological disorders. Statistical t-test was
      used in order to compare means of fundamental frequencies (F0) of cries among
      pathologies, as well as contingency tables for qualitative variables and melodic
      form. RESULTS: No significant differences of F0 were found by applying the t-test
      among pathologies. Time of inspiration in breathing disorders is higher compared
      with other groups. Infants with deafness and neurological disorders present poor
      melodic forms. Qualitative analysis revealed more often glottal roll and vibrato.
      CONCLUSIONS: Cry analysis is clinically useful for early detection of diseases in
      newborns as a result of alterations in the central nervous system that are
      reflected in phonoarticulatory and respiratory functions for sound emission.

PMID- 22472147
TI  - Evaluation of a respiratory rehabilitation program in children with scoliosis.
AB  - BACKGROUND: Thoracic scoliosis is a lateral curvature of the spine associated
      with restrictive lung defects, manifested by a decrease in respiratory function
      tests. We undertook this study to evaluate the effect of a respiratory
      rehabilitation program over lung function in children with scoliosis. METHODS: We
      carried out a prospective and deliberate intervention study including 25
      consecutive patients, aged 6 to 18 years, diagnosed with thoracic scoliosis. The
      respiratory rehabilitation program was structured into two phases: institutional
      and private residence. Statistical analysis was carried out using descriptive
      parameters and paired t-test and Wilcoxon signed-ranks test. Spearman correlation
      was used to measure intensity of association among variables. Statistical
      significance was considered when p <0.05. RESULTS: Idiopathic scoliosis was
      present in 52% of patients, with right dorsal curvature in 72%. Cobb angle
      average was 50.6 degrees  +/- 29.7 degrees . Most importantly, we found a
      negative correlation between this angle on left curvature and lung function.
      Initially, the main respiratory symptoms were dyspnea with poor effort tolerance
      in 52%. After treatment, 88% of patients were asymptomatic and only 4% presented
      poor effort tolerance. Oxygen saturation and forced vital capacity percentage had
      a significant increment after the program. CONCLUSION: Respiratory rehabilitation
      has a positive effect on increasing pulmonary function of children with
      scoliosis.

PMID- 22472148
TI  - Diabetic retinopathy and complexity of retinal surgery in a general hospital.
AB  - BACKGROUND: Usual retinal surgery (vitrectomy or surgery for retinal detachment)
      may require additional procedures to deal with complex cases, which increase time
      and resource use and delay access to treatment. We undertook this study to
      identify the proportion of primary retinal surgeries that required complex
      procedures and the associated causes. METHODS: We carried out an observational,
      descriptive, cross-sectional, retrospective study. Patients with primary retinal
      surgery were evaluated (January 2007-December 2010). The proportion and 95%
      confidence intervals (CI) of preoperative diagnosis and cause of the disease
      requiring retinal surgery as well as the causes for complex retinal surgery were
      identified. Complex retinal surgery was defined as that requiring lens
      extraction, intraocular lens implantation, heavy perfluorocarbon liquids,
      silicone oil tamponade or intravitreal drugs, in addition to the usual surgical
      retinal procedure. The proportion of complex retinal surgeries was compared among
      preoperative diagnoses and among causes (chi(2), odds ratio [OR]). RESULTS: We
      studied 338 eyes. Mean age of subjects was 53.7 years, and there were 49%
      females. The most common diagnoses were vitreous hemorrhage (27.2%) and
      rhegmatogenous retinal detachment (24.6%). The most common cause was diabetes
      (50.6%); 273 eyes required complex surgery (80.8%, 95% CI: 76.6-85). The
      proportion did not differ among diagnoses but was higher in diabetic retinopathy
      (89%, p <0.001, OR 3.04, 95% CI: 1.63-5.7). CONCLUSIONS: Of the total sample,
      80.8% of eyes required complex surgical procedures; diabetic retinopathy
      increased by 3-fold the probability of requiring these complex procedures. Early
      treatment of diabetic retinopathy may reduce the proportion of complex retinal
      surgery by 56%.

PMID- 22472149
TI  - Disparity between foveal thickness and macular volume in diabetic macular edema.
AB  - BACKGROUND: Optical coherence tomography (OCT) quantifies changes of foveal
      thickness and macular volume after photocoagulation in diabetic macular edema.
      Macular volume evaluates the whole macula, but it may underestimate changes in
      foveal thickness induced by photocoagulation. We undertook this study to evaluate
      the concordance between macular volume and foveal thickness for identifying
      clinically significant changes of retinal thickness after photocoagulation for
      diabetic macular edema. METHODS: We carried out an observational, retrospective,
      longitudinal, analytical study. Center point thickness (CPT), central subfield
      mean thickness (CSMT) and macular volume were measured with OCT before
      photocoagulation and 3 weeks after in diabetic patients with focal macular edema
      (January 2006--January 2010). Concordance among variables to detect clinically
      significant changes (CPT >17%, CSMT >11%, macular volume >3%) was identified
      using the kappa test. RESULTS: Sixty eight eyes were included; 47 eyes had
      nonproliferative retinopathy (69.1%). CPT increased significantly in 14.7% of the
      sample; CSMT in 8.8%, and macular volume in 11.8%. CPT decreased significantly in
      4.4%, CSMT in 8.8%, and macular volume in 42.6%. Concordance was regular for CPT
      and CSMT increased (57%). Concordance was good for CPT and CSMT decreased (64%).
      Concordance was regular for CSMT and macular volume decreased in eyes with center
      involvement (43%). The remaining concordances were poor. DISCUSSION: Two
      independent events happen after focal photocoagulation: involution of the
      original thickening and increase in CPT. In order to detect both events,
      evaluation of either foveal thickness alone or macular volume alone is
      insufficient. CONCLUSION: Identifying the efficacy and safety of treatments for
      diabetic macular edema requires simultaneous measurement of CPT and macular
      volume.

PMID- 22472150
TI  - Analysis of oropharyngeal dysphagia through fibroendoscopy evaluation of
      swallowing in patients with Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) has a high incidence in Mexico and is
      estimated at approximately 500,000 patients. One of the main clinical
      manifestations of PD is dysphagia, which is the difficult passage of food from
      the mouth to the stomach. The aim of this study was to assess oropharyngeal
      dysphagia through fibroendoscopy evaluation of swallowing in patients with PD.
      METHODS: We conducted a census sample of patients with PD: 17 males and 10
      females, aged >49 years. Clinical history, physical examination and neurological
      evaluation of swallowing fibroendoscopy were carried out. RESULTS: Of the
      symptomatic patients, 16 patients (59.25%) reported dysphagia. Fibroendoscopic
      evaluation demonstrated swallowing disorders in 25 patients (92.59%). The main
      findings were poor bolus control in 19 patients (70.37%), deficits in bolus
      propulsion in 25 patients (92.59%), impaired swallowing in 14 patients (51.85%),
      fractional swallowing in 11 patients (40.74%), reduced epiglottic tilting in 11
      patients (48.14%), food residue in vallecula in 24 patients (88.88%) and piriform
      sinus in 19 patients (70.37%). There was no correlation between duration of PD
      and degree of involvement of oropharyngeal dysphagia. CONCLUSIONS: Oropharyngeal
      dysphagia in patients with PD is a common symptom and can range from the oral
      cavity to the upper esophageal sphincter. Early onset of severe dysphagia is
      exceptional in this disease and should alert the clinician to the diagnostic
      possibility of parkinsonism.

PMID- 22472151
TI  - Heller myotomy and laparoscopic fundoplication in achalasia. A retrospective
      experience.
AB  - BACKGROUND: Laparoscopic myotomy associated with fundoplication is a useful
      therapeutic resource for the treatment of achalasia. The aim of the study was to
      analyze the outcomes of the surgical treatment of achalasia in a group of
      patients treated at the Hospital Naval de la Secretaria de Marina and at the
      Hospital Espanol in Veracruz during a 6-year period. METHODS: Eleven patients
      were submitted to myotomy and fundoplication. Variables analyzed were age,
      gender, symptom duration, surgical complications, surgical time, day/stay, and
      postoperative morbidity. RESULTS: Mean age was 41.7 years +/- 7.69 years; 63.64%
      of the patients were male and 36.36% were female. Average time from symptom onset
      was 2.5 +/- 1.38 years. All patients had received previous unsuccessful medical
      and endoscopic treatment. Diagnosis was confirmed by esophagogram, endoscopy and
      manometry. All patients underwent Heller myotomy and fundoplication. Operative
      time was 140.4 +/- 26.2 min. Average days/stay was 3.7 +/- 1.4 days.
      Postoperative course was satisfactory in all patients and there was no
      perioperative mortality. Average follow-up was 3.8 +/- 2.3 years. CONCLUSIONS: In
      our group, laparoscopic myotomy with fundoplication was a safe procedure offering
      excellent results comparable with those published in the literature. There is
      controversy about the type of fundoplication; therefore, the choice is at the
      discretion of the surgeon.

PMID- 22472152
TI  - Gastrointestinal stromal tumors: diagnosis and treatment.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common
      mesenchymal neoplasms of the digestive tract. They originate from the
      interstitial cells of Cajal and are characterized by the overexpression of KIT
      protein (tyrosine kinase). Their prognosis has improved significantly with the
      discovery of imatinib mesylate for advanced GIST treatment. METHODS: We carried
      out a retrospective, descriptive study of GISTs diagnosed in our center during
      the past 5 years. We excluded patients with incidental diagnoses in the context
      of other pathologies because GIST did not affect outcome or prognosis. The
      variables studied were clinical characteristics, location, size, imaging
      techniques, resectability, neoadjuvant imatinib, surgical technique, histology,
      immunohistochemistry, prognostic classification of Fletcher, morbidity,
      monitoring, and disease-free and overall survival. RESULTS: Nineteen patients
      were diagnosed (14 males/5 females) with a mean age of 63 years (range: 30-84
      years). Diagnosis was incidental in eight patients (42%). Tumor location of the
      remaining 11 patients (58%) was six tumors of the small intestine (55%), four
      gastric (36%) and one rectal (9%). Predominant gastrointestinal bleeding and
      anemia were diagnosed mainly by abdominal computed tomography (CT). At diagnosis,
      nine patients were considered resectable with radical intent (82%) and the other
      two patients (18%) received neoadjuvant treatment with a favorable response after
      6 months. Three patients were treated with imatinib after surgery (33%). Median
      survival was 34 months (range: 5-58 months). CONCLUSIONS: Diagnosis of GIST is
      often incidental. The predominant clinical symptom is usually gastrointestinal
      bleeding and anemia and the most widely used imaging test is CT. Treatment is
      surgical unless advanced GIST is diagnosed, which will be treated with imatinib
      mesylate neoadjuvant therapy. A multidisciplinary approach to this pathology is
      essential, a fact that affects prognosis and patient survival.

PMID- 22472153
TI  - Surgical management of simple liver cysts.
AB  - BACKGROUND: To date there is no consensus about the treatment of choice for
      symptomatic or complicated simple liver cysts. METHODS: A retrospective study of
      all patients diagnosed with simple liver cyst surgically managed at Ramon y Cajal
      Hospital during the period between 1998 and 2008 was performed. RESULTS: We
      analyzed 21 patients, 18 females (85.7%) and three males (14.3%) with a mean age
      of 64.2 years. Ten patients (47.6%) were asymptomatic. During follow-up, cyst
      growth was determined. Three patients (14.3%) presented an infected simple liver
      cyst. Seven patients (33.3%) presented abdominal pain and one patient (4.8%)
      reported an abdominal mass during self-examination. Treatment consisted of
      unroofing and cyst drainage in 18 patients (85.7%) and cyst enucleation in three
      patients (14.3%). Postoperative complications appeared in two patients (9.6%).
      There was no mortality. Pathology revealed simple liver cyst in 17 patients
      (80.9%) and liver cystadenoma in four (19.1%). The latter were reoperated for
      complete cyst resection. Recurrence rate was 23.5% (four cases) for the simple
      liver cysts. In all cases, unroofing was performed. CONCLUSION: In some cases,
      cystadenomas show ultrasonographic and radiological features similar to simple
      liver cysts, implying an incorrect surgical approach. We recommend performing an
      intraoperative biopsy of all resected liver cysts to confirm its nature.
      Unroofing is associated with a high recurrence rate (>20%). Therefore, we propose
      cyst enucleation as the best surgical treatment.

PMID- 22472154
TI  - Effect of endovenous morphine vs. ketorolac on proinflammatory cytokines during
      postoperative analgesia in laparoscopic cholecystectomy.
AB  - BACKGROUND: Postoperative pain is the main symptom following a surgical event and
      is related to an inflammatory process involving cytokine secretion. This type of
      pain is usually treated with opioids such as morphine, whose analgesic efficacy
      is well known. However, it is unknown when compared with ketorolac in measuring
      proinflammatory cytokine levels. The aim of this study was to determine the
      postoperative analgesic effect with endovenous morphine on proinflammatory
      cytokine levels in patients who underwent laparoscopic choleystectomy. METHODS:
      We studied 40 patients who underwent laparoscopic cholecystectomy. Patients were
      randomized to receive morphine (0.05 mg/kg) or ketorolac (0.2 mg/kg) IV during
      gallbladder extraction and after the surgical event at the following dose:
      morphine (0.15 mg/kg) or ketorolac (0.7 mg/kg) for 40 min. Clinical evaluations
      included were hemodynamic, analgesic with visual analogue scale, and sedation
      (Ramsay scale). IL-1beta and TNF-a were measured pre- and postoperatively and
      after 12 h. Safety profile was evaluated with hemodynamic constants. Statistical
      analysis was carried out using Mann-Whitney U test and Fisher exact test.
      RESULTS: TNF-a was increased significantly in the immediate postoperative period
      and after 12 h in the morphine group. IL-1beta was not detected preoperatively,
      in the immediate postoperative period and 12 h after surgery the levels were
      similar in both groups. The main adverse event was respiratory depression, which
      occurred in the morphine group. CONCLUSIONS: Proinflammatory cytokines were
      increased after surgery, particularly TNF-a in the group receiving morphine. The
      use of morphine is safe postoperatively.

PMID- 22472155
TI  - Merkel cell carcinoma: case report and literature review.
AB  - BACKGROUND: Merkel cell carcinoma is an aggressive neuroendocrine cell carcinoma
      arising in the epidermis of patients aged >60 years. This lesion is found in sun
      exposed areas and presents as a small violet raised nodule. It is usually
      painless and rapidly growing. Although its clinical presentation and
      characteristic histology are usually sufficient, immunohistochemical features are
      helpful in making an accurate diagnosis. CLINICAL CASE: We present the case of a
      62-year-old male with epidermoid carcinoma of the lung who was treated with
      surgery and local radiation for 2 months. He presented a painless 8-cm
      subcutaneous mass of some weeks of evolution, without inflammatory signs.
      Computerized tomography demonstrated a mass of probable lymph node origin. Fine
      needle aspiration biopsy (FNAB) reported malignant cells and excisional surgery
      of the mass was performed, revealing a subcutaneous Merkel cell carcinoma.
      CONCLUSIONS: Merkel cell carcinoma is a rare entity that develops in mature
      patients, often in sun-exposed areas, and presents cutaneous injury in intact
      skin. Definitive diagnosis is done using immunohistochemistry.

PMID- 22472156
TI  - Primary pulmonary biphasic synovial sarcoma: a case report and literature review.
AB  - BACKGROUND: Primary synovial sarcomas of the lung are extremely rare,
      constituting 0.1% to 0.5% of lung cancers. The first case was reported by
      Gaertner in 1996. CLINICAL CASE: We present the case of a 15-year-old female who
      presented with cough, white-colored secretions, right-sided chest pain and
      progressive dyspnea. Physical examination revealed increased exertion during
      breathing with no cyanosis. The presence of right scapular pulmonary condensation
      syndrome was observed. Chest x-ray demonstrated homogeneous opacity occupying the
      lower two thirds of the right hemithorax. Posterolateral thoracotomy with right
      lower and medium lobectomy was performed. Because there was evidence of upper
      lobe tumor, it was decided to carry out a right pneumonectomy. Histopathological
      diagnosis was biphasic synovial sarcoma. CONCLUSIONS: The presentation of
      pulmonary synovial sarcoma generally shows a peripheral location with a
      nonencapsulated and well-circumscribed tumor. Size ranges from 0.6 to 17 cm
      (mean: 5 cm). Histology is often characterized by a monophasic pattern. Diagnosis
      is difficult except for a uniform spindle cell pattern. Most synovial sarcomas
      show immunoreactivity for cytokeratin and/or epithelial membrane antigen.
      Cytogenetic characteristic of synovial sarcoma are t(X; 18)(p11, q11). Patient
      prognosis for pulmonary synovial sarcoma is poor with an overall 5-year survival
      rate of 50%.

PMID- 22472157
TI  - Delayed intestinal obstruction due to posttraumatic diaphragmatic hernia.
AB  - BACKGROUND: Diaphragmatic rupture can be missed during trauma diagnosis.
      Different pressures between the thorax and the abdomen allow the abdominal
      viscera to herniate into the chest cavity. Cardiorespiratory and abdominal
      symptoms may appear later due to passive compression and incarceration,
      respectively. CLINICAL CASE: We report the case of a 52-year-old female with
      abdominal pain and vomiting. Chest x-ray demonstrated an elevation of the right
      hemidiaphragm, and computed tomography showed herniation of small bowel and colon
      into the chest cavity with dilated small bowel due to a diaphragmatic hernia.
      CONCLUSIONS: History of traumatic events should be considered with high suspicion
      in the diagnostic process to avoid delayed diagnosis of this condition. The
      nonspecific symptoms of this condition often lead the patient to consult
      different specialists. A multidisciplinary approach is required and aimed at
      preventing an unnecessary increase of morbidity and mortality.

PMID- 22472158
TI  - Incarcerated umbilical hernia as the debut of abdominal actinomycosis.
AB  - BACKGROUND: Abdominal actinomycosis is a rare infection with a difficult
      diagnosis that can simulate multiple surgical scenarios such as neoplasms or
      complications of inflammatory bowel disease. CLINICAL CASE: We present the case
      of a 69-year-old female who underwent emergency surgery due to a difficult and
      painful tumor, suggesting an incarcerated umbilical hernia. Whitish lesions were
      discovered in the abdominal wall and a stenotic colonic mass was managed similar
      to a neoplasm. Anatomopathological study showed abdominal actinomycosis,
      requiring a lengthy course with penicillin. CONCLUSION: Actinomycosis infection
      is a chronic disease with granulomatous lesions and areas of fibrosis. Its
      incidence is increasing and the location usually is cervicofacial. The great
      challenge of this pathology lies in the diagnosis because it simulates different
      diseases of diverse natures. This type of infection can be treated successfully
      with drugs if the etiology is identified in a timely manner. However, in the case
      of our patient, the manner of presentation made diagnosis more difficult prior to
      surgical trauma.

PMID- 22472159
TI  - Spontaneous uterine rupture: report of two cases.
AB  - BACKGROUND: Uterine rupture is a rare entity with an incidence of 0.07% and is a
      cause of perinatal mortality. Dehiscence of previous uterine scar is the most
      important cause, but other causes have been reported such as placenta percreta.
      Almost 80% of uterine ruptures are spontaneous and its complications lead to an
      elevated mortality rate for the mother and the fetus. CLINICAL CASES: Case 1. We
      present the case of a 28-year-old female with no previous relevant medical
      history. The patient was 20 weeks pregnant with a diagnosis of uterus didelphys
      (double uterus) with lower placental implantation with normal pregnancy evolution
      at the time. Evolution of her illness was with intense abdominal pain and
      transvaginal bleeding. Case 2. We present the case of a 20-year-old female with a
      history of spontaneous abortion 1 year prior. The patient denied pregnancy and
      even reported her last menstruation date on 3/23/09. She began with sudden
      abdominal pain associated with two episodes of diarrhea, dizziness and fainting.
      CONCLUSION: Uterine rupture is a rare clinical entity with an elevated perinatal
      mortality. Clinical suspicion is of vital important for early diagnosis and
      timely treatment.

PMID- 22472160
TI  - Lung transplantation with uncontrolled non-heart-beating donor. Review.
AB  - The discrepancy between organ availability and the increasing amount of patients
      on the waiting list has prompted the development of medical strategies to
      increase the usable organs, including the search for alternative sources of
      donation, organ optimization and extension of the criteria for donation. The
      recovery of lungs from non-heart-beating donors (NHBD) is a concept in which
      death is declared based on cardiopulmonary criteria rather than the currently
      used definition of "brain death." Obtaining NHBD lungs is currently practiced in
      many centers. In this review we discuss the current state of lung transplantation
      from uncontrolled NHBD.

PMID- 22472161
TI  - Practice guidelines for the implementation of a quality program in
      thromboprophylaxis and treatment management in patients with venous
      thromboembolic disease.
AB  - BACKGROUND: Venous thromboembolic disease is a major cause of morbidity and
      hospital mortality worldwide. Although exact figures are unknown in Mexico,
      achieving uniformity of criteria among the specialties involved in the
      prophylaxis and treatment will offer a clearer picture and contribute to a more
      rational and interdisciplinary approach in order to improve the quality of care
      for patients and increase the level of awareness of this entity. DISCUSSION: For
      the preparation of this document, a total of 11 medical specialists from Mexico
      City and the interior of the country met along with a highly experienced
      professional from Chicago, IL, USA with wide experience in the field and
      knowledge of methodology for the development of a management algorithm for
      prophylaxis in at-risk patients of venous thromboembolic disease. The expert
      group met in plenary working sessions, managed uniform criteria and reached
      consensus agreement by issuing a series of useful recommendations for the care of
      patients with venous thromboembolism in Mexican hospitals. CONCLUSIONS: In Mexico
      there is the need to develop and disseminate guidelines on thromboprophylaxis and
      treatment of venous thromboembolic disease because of the wide disparity of views
      or simple misinformation, leading to diagnostic and treatment behaviors unique to
      each institution.

PMID- 22472162
TI  - Oxidized regenerated cellulose granuloma mimicking recurrent mass lesion after
      laparoscopic nephron sparing surgery.
AB  - INTRODUCTION: Achieving hemostasis in laparoscopic nephron sparing surgery
      (LNSS), a technically demanding procedure, is challenging. Absorbable hemostatic
      agents, such as oxidized regenerated cellulose (ORC) are frequently used for
      hemostasis in laparoscopic nephron sparing surgery. Retention of this material is
      a very rare situation. PRESENTATION OF THE CASE: We are presenting a case of ORC
      granuloma after nephron sparing surgery for renal cell carcinoma (RCC) mimicking
      recurrent renal mass. A 50-year-old woman diagnosed with upper pole renal mass
      underwent laparoscopic nephron sparing surgery. Oxidized regenerated cellulose
      was used to achieve hemostasis for an oozing from the perirenal tissue. Resection
      confirmed RCC. Imaging at 6th month follow-up revealed a lesion with contrast
      enhancement at the location of the adrenal gland. Positron emission tomography
      suggested inflammation or metastasis. Histopathological evaluation of the mass
      revealed foreign body granuloma. DISCUSSION: Laparoscopic nephron sparing surgery
      is becoming a standardized treatment of select renal tumors. Hemostatic agents,
      such as ORC, are frequently used to minimize complications in LNSS. In case of
      ORC application, which is completely absorbed in 8 weeks, to or to a location
      with close proximity to the primary resection site, surgical granuloma formation
      should be considered. However its use should not be discouraged and biopsy may be
      considered for definitive diagnosis. CONCLUSION: Oxidized regenerated cellulose
      granuloma may mimic different entities such as including invasive carcinoma. Thus
      it is of utmost importance, if ORC was used during LNSS, the location and use of
      this material should be noted precisely.

PMID- 22472163
TI  - Spontaneous virologic suppression in HIV controllers is independent of delayed
      type hypersensitivity test responsiveness.
AB  - BACKGROUND: Delayed-type hypersensitivity (DTH) testing, an in vivo assessment of
      cell-mediated immunity, is a predictor of HIV disease progression beyond CD4 cell
      count. We investigated whether preserved DTH responsiveness was characteristic of
      HIV controllers compared to non-controllers and individuals on suppressive HAART.
      FINDINGS: DTH testing consisted of >= 3 recall antigens applied approximately
      every 6 months. DTH responses were classified by the number of positive skin
      tests: anergic (0), partial anergic (1), or non-anergic (>= 2). HIV controllers
      were compared to treatment naive non-controllers (n = 3822) and a subgroup of non
      controllers with VL < 400 copies/mL on their initial HAART regimen (n = 491). The
      proportion of non-anergic results at first DTH testing was similar for HIV
      controllers compared to non-controllers (81.9% vs. 77.6%; P = 0.22), but tended
      to be greater in HIV controllers compared to the HAART subgroup (81.9% vs. 74.5%;
      P = 0.07). Complete anergy was observed in 14 (10.1%) HIV controllers with CD4
      counts >= 400 cells/uL. For longitudinal testing, the average percentage of non
      anergic DTH determinations per participant was higher in HIV controllers compared
      to non-controllers (81.2 +/- 31.9% vs. 70.7 +/- 36.8%; P = 0.0002), however this
      difference was eliminated with stratification by CD4 count: 200-399 (83.4 +/-
      35.6% vs. 71.9 +/- 40.9%; P = 0.15) and > 400 cells/uL (81.2 +/- 31.5% vs. 80.4
      +/- 32.7%; P = 0.76). CONCLUSIONS: Spontaneous virologic control was not
      associated with DTH responsiveness, and several HIV controllers were anergic
      despite having elevated CD4 counts. These findings suggest that cellular immunity
      assessed by DTH is not a principal factor contributing to spontaneous virologic
      suppression in HIV controllers.

PMID- 22472165
TI  - "This is my way": reimagining disability, in/dependence and interconnectedness of
      persons and assistive technologies.
AB  - PURPOSE: Postmodernism provides a radical alternative to the dominant discourses
      of Western societies that emphasize autonomy and independence. It suggests a
      reimagining of the relationship between the self and the body and the
      increasingly blurred boundaries between biology and machine. The purpose of this
      article is to explore in/dependence through a discussion of interconnectedness of
      persons and assistive technologies. KEY MESSAGES: Drawing on postmodern theories,
      we discuss the interconnections inherent in disability experiences through the
      case example of Mimi, an adolescent girl with severe physical disabilities. We
      consider how Mimi, her assistive technologies and her parents can be viewed as
      assemblages of bodies/technologies/subjectivities that together achieve a set of
      practices. An examination of these various couplings suggests different
      understandings of disability that open up possibilities for multiple connections
      and reimagines dependencies as connectivities. CONCLUSIONS: Connectivity can be
      embraced to explore multiple ways of being-in-the-world for all persons and
      problematizes the goals of independence inherent in rehabilitation practices.

PMID- 22472164
TI  - Strategies for modulating the inflammatory response after decompression from
      abdominal compartment syndrome.
AB  - BACKGROUND: Management of the open abdomen is an increasingly common part of
      surgical practice. The purpose of this review is to examine the scientific
      background for the use of temporary abdominal closure (TAC) in the open abdomen
      as a way to modulate the local and systemic inflammatory response, with an
      emphasis on decompression after abdominal compartment syndrome (ACS). METHODS: A
      review of the relevant English language literature was conducted. Priority was
      placed on articles published within the last 5 years. RESULTS/CONCLUSION: Recent
      data from our group and others have begun to lay the foundation for the concept
      of TAC as a method to modulate the local and/or systemic inflammatory response in
      patients with an open abdomen resulting from ACS.

PMID- 22472166
TI  - Synthesis and antikinetoplastid activities of 3-substituted quinolinones
      derivatives.
AB  - A new family of quinolinone derivatives has been synthesized and evaluated for
      their antikinetoplastid activities against Leishmania donovani and Trypanosoma
      brucei brucei. Results from these structure-activity relationship studies enabled
      identification of compounds 3a and 4g as the most active compounds against L.
      donovani promastigotes and amastigotes parasites (IC(50) values in a range of 2
      11 MUM). Additionally, compound 3b has emerged from this study as the most active
      compound in the series against T. b. brucei with a MEC value of 12 MUM. These
      three compounds are worth of further in vivo evaluation.

PMID- 22472167
TI  - Studies on gambogic acid (IV): Exploring structure-activity relationship with
      IkappaB kinase-beta (IKKbeta).
AB  - Previously we have reported a series of gambogic acid's analogs and have
      identified a compound that possessed comparable in vitro growth inhibitory effect
      as gambogic acid. However, their target protein as well as the key pharmacophoric
      motifs on the target have not been identified yet. Herein we report that gambogic
      acid and its analogs inhibit the activity of IkappaB Kinase-beta (IKKbeta)
      through suppressing the activation of TNFalpha/NF-kappaB pathway, which in turn
      induces A549 and U251 cell apoptosis. IKKbeta can serve as one of gambogic acid's
      targets. The preparation of the compounds was carefully discussed in the article.
      Caged 4-oxa-tricyclo[4.3.1.0(3,7)]dec-2-one xanthone, which was identified as the
      pharmacophoric scaffold, represents a promising therapeutic agent for cancer and
      useful probe against NF-kappaB pathway.

PMID- 22472169
TI  - Diastereoselective addition of allyltitanocenes to cyclic enones.
AB  - The reaction of allyltitanocenes with five- to seven-membered cyclic enones
      proceeded with good to high diastereoselectivity depending on the ring size of
      enones. The stereochemistry of the major isomers produced by the reaction of
      cinnamyltitanocene was opposite to that of crotyltitanocene.

PMID- 22472168
TI  - Nicotinic ACh receptors in the hippocampus: role in excitability and plasticity.
AB  - INTRODUCTION: The nicotinic ACh receptors (nAChRs) are in the cys-loop family of
      ligand-gated ion channels. They are widely expressed throughout the brain,
      including in the hippocampus where they are thought to be involved in regulating
      excitability, plasticity, and cognitive function. In addition, dysfunction in
      hippocampal nAChRs has been linked to a variety of neurological disorders and
      diseases, including Alzheimer's disease, schizophrenia, and epilepsy. In order to
      understand how to treat nAChR-related disorders and diseases, it is critical to
      understand how these receptors participate in normal brain function; this entails
      not only understanding the biophysical properties of ion channel function and
      their pattern of expression but also how these receptors are regulating
      excitability and circuit behavior. DISCUSSION: The primary cholinergic input to
      the hippocampus comes from the medial septum and diagonal band of Broca; however,
      the mechanistic details are unknown of how activation of cholinergic receptors,
      either through exogenous nAChR ligands or the activation of endogenous
      acetylcholine release, regulates hippocampal network activity. This entails
      direct study of the excitatory and inhibitory neuronal networks, as well as the
      role of nonneuronal cells, in regulating hippocampal function. CONCLUSIONS: Here,
      I will review the latest work from my laboratory in which we have attempted to do
      just that, with the overall goal of learning more about the role of the
      hippocampal nAChR in synaptic plasticity.

PMID- 22472170
TI  - A novel approach for studying the temporal modulation of embryonic skeletal
      development using organotypic bone cultures and microcomputed tomography.
AB  - Understanding the structural development of embryonic bone in a three dimensional
      framework is fundamental to developing new strategies for the recapitulation of
      bone tissue in latter life. We present an innovative combined approach of an
      organotypic embryonic femur culture model, microcomputed tomography (MUCT) and
      immunohistochemistry to examine the development and modulation of the three
      dimensional structures of the developing embryonic femur. Isolated embryonic
      chick femurs were organotypic (air/liquid interface) cultured for 10 days in
      either basal, chondrogenic, or osteogenic supplemented culture conditions. The
      growth development and modulating effects of basal, chondrogenic, or osteogenic
      culture media of the embryonic chick femurs was investigated using MUCT,
      immunohistochemistry, and histology. The growth and development of noncultured
      embryonic chick femur stages E10, E11, E12, E13, E15, and E17 were very closely
      correlated with increased morphometric indices of bone formation as determined by
      MUCT. After 10 days in the organotpyic culture set up, the early aged femurs (E10
      and E11) demonstrated a dramatic response to the chondrogenic or osteogenic
      culture conditions compared to the basal cultured femurs as determined by a
      change in MUCT morphometric indices and modified expression of chondrogenic and
      osteogenic markers. Although the later aged femurs (E12 and E13) increased in
      size and structure after 10 days organotpypic culture, the effects of the
      osteogenic and chondrogenic organotypic cultures on these femurs were not
      significantly altered compared to basal conditions. We have demonstrated that the
      embryonic chick femur organotpyic culture model combined with the MUCT and
      immunohistochemical analysis can provide an integral methodology for
      investigating the modulation of bone development in an ex vivo culture setting.
      Hence, these interdisciplinary techniques of MUCT and whole organ bone cultures
      will enable us to delineate some of the temporal, structural developmental
      paradigms and modulation of bone tissue formation to underpin innovative skeletal
      regenerative technology for clinical therapeutic strategies in musculoskeletal
      trauma and diseases.

PMID- 22472171
TI  - Do hospital treatments represent a 'teachable moment' for quitting smoking? A
      study from a stage-theoretical perspective.
AB  - Hospital treatments are assumed to be a 'teachable moment'. This phenomenon,
      however, is only poorly conceptualised and untested. A stage-theoretical
      perspective implies that a cueing event such as hospital treatments is a
      teachable moment if a stage progression, change of cognitions, or both occur.
      This concept is examined in a cross-sectional study by comparing smokers in two
      treatment settings, an emergency department (ED) and inpatient treatment after
      elective surgery, with smokers in a control setting. Setting differences were
      hypothesised in stage distribution, and levels of and stage differences in social
      cognitive factors under control for possible confounders. Stage, social-cognitive
      factors and possible confounders were assessed in 185 ED smokers, 193 inpatient
      smokers and 290 control smokers. Compared to control smokers, ED and inpatient
      smokers were in higher stages; they perceived fewer risks and cons; inpatient
      smokers reported more concrete plans. Stage differences in self-efficacy among ED
      and inpatient smokers differed from those among control smokers, but the former
      corresponded more strongly to the theoretical stage assumptions. The results
      suggest that hospital treatments lead to a stage progression and change of
      corresponding cognitions, and thus represent a 'teachable moment'. Stage-matched
      interventions should be provided but consider differences in cognitions to be
      effective.

PMID- 22472172
TI  - Genome-scale metabolic reconstructions of Pichia stipitis and Pichia pastoris and
      in silico evaluation of their potentials.
AB  - BACKGROUND: Pichia stipitis and Pichia pastoris have long been investigated due
      to their native abilities to metabolize every sugar from lignocellulose and to
      modulate methanol consumption, respectively. The latter has been driving the
      production of several recombinant proteins. As a result, significant advances in
      their biochemical knowledge, as well as in genetic engineering and fermentation
      methods have been generated. The release of their genome sequences has allowed
      systems level research. RESULTS: In this work, genome-scale metabolic models
      (GEMs) of P. stipitis (iSS884) and P. pastoris (iLC915) were reconstructed.
      iSS884 includes 1332 reactions, 922 metabolites, and 4 compartments. iLC915
      contains 1423 reactions, 899 metabolites, and 7 compartments. Compared with the
      previous GEMs of P. pastoris, PpaMBEL1254 and iPP668, iLC915 contains more genes
      and metabolic functions, as well as improved predictive capabilities. Simulations
      of physiological responses for the growth of both yeasts on selected carbon
      sources using iSS884 and iLC915 closely reproduced the experimental data.
      Additionally, the iSS884 model was used to predict ethanol production from xylose
      at different oxygen uptake rates. Simulations with iLC915 closely reproduced the
      effect of oxygen uptake rate on physiological states of P. pastoris expressing a
      recombinant protein. The potential of P. stipitis for the conversion of xylose
      and glucose into ethanol using reactors in series, and of P. pastoris to produce
      recombinant proteins using mixtures of methanol and glycerol or sorbitol are also
      discussed. CONCLUSIONS: In conclusion the first GEM of P. stipitis (iSS884) was
      reconstructed and validated. The expanded version of the P. pastoris GEM, iLC915,
      is more complete and has improved capabilities over the existing models. Both
      GEMs are useful frameworks to explore the versatility of these yeasts and to
      capitalize on their biotechnological potentials.

PMID- 22472173
TI  - No difference in intra-arterial and intramuscular delivery of autologous bone
      marrow cells in patients with advanced critical limb ischemia.
AB  - Stem cell therapy has been proposed to be an alternative therapy in patients with
      critical limb ischemia (CLI), not eligible for endovascular or surgical
      revascularization. We compared the therapeutic effects of intramuscular (IM) and
      intra-arterial (IA) delivery of bone marrow cells  (BMCs) and investigated the
      factors associated with therapeutic benefits. Forty-one patients (mean age, 66 +/
      10 years; 35 males) with advanced CLI (Rutherford category, 5 and 6) not
      eligible for revascularization were randomized to treatment with 40 ml BMCs using
      local IM (n  = 21) or selective IA infusion (n = 20). Primary endpoints were limb
      salvage and wound healing. Secondary endpoints were changes in transcutaneous
      oxygen pressure (tcpO(2)), quality-of-life questionnaire (EQ5D), ankle-brachial
      index (ABI), and pain scale (0-10). Patients  with limb salvage and wound healing
      were considered to be responders to BMC therapy. At 6-month follow-up, overall
      limb salvage was 73% (27/37) and 10 subjects underwent major amputation. Four
      patients died unrelated to stem cell therapy. There was significant improvement
      in tcpO(2)  (15 +/- 10 to 29 +/- 13 mmHg, p < 0.001), pain scale (4.4 +/- 2.6 to
      0.9 +/- 1.4, p < 0.001), and EQ5D (51 +/- 15 to 70 +/- 13, p < 0.001) and a
      significant decrease in the Rutherford category of CLI (5.0 +/- 0.2 to 4.3 +/- 
      1.6, p < 0.01). There were no differences among functional parameters in patients
      undergoing IM versus IA delivery. Responders (n = 27) were characterized by
      higher CD34(+) cell counts in the bone marrow concentrate (CD34(+) 29 +/-
      15*10(6)  vs. 17 +/- 12*10(6), p < 0.05) despite a similar number of total
      nucleated cells (4.3 +/- 1.4*10(9) vs. 4.1 +/- 1.2*10(9), p = 0.66) and by a
      lower level of C-reactive protein (18 +/- 28 vs. 100 +/-  96 mg/L, p < 0.05) as
      well as serum leukocytes (8.3 +/- 2.1*10(9)/L vs. 12.3 +/- 4.5*10(9)/L, p < 0.05)
      as compared with nonresponders (10 patients). Both IM and IA delivery of
      autologous stem cells are effective therapeutic strategies  in patients with CLI.
      A higher concentration of CD34(+) cells and a lower degree of inflammation are
      associated with better clinical therapeutic responses.

PMID- 22472174
TI  - SSBP2 variants are associated with survival in glioblastoma patients.
AB  - PURPOSE: Glioblastoma is a devastating, incurable disease with few known
      prognostic factors. Here, we present the first genome-wide survival and
      validation study for glioblastoma. EXPERIMENTAL DESIGN: Cox regressions for
      survival with 314,635 inherited autosomal single-nucleotide polymorphisms (SNP)
      among 315 San Francisco Adult Glioma Study patients for discovery and three
      independent validation data sets [87 Mayo Clinic, 232 glioma patients recruited
      from several medical centers in Southeastern United States (GliomaSE), and 115
      The Cancer Genome Atlas patients] were used to identify SNPs associated with
      overall survival for Caucasian glioblastoma patients treated with the current
      standard of care, resection, radiation, and temozolomide (total n = 749). Tumor
      expression of the gene that contained the identified prognostic SNP was examined
      in three separate data sets (total n = 619). Genotype imputation was used to
      estimate hazard ratios (HR) for SNPs that had not been directly genotyped.
      RESULTS: From the discovery and validation analyses, we identified a variant in
      single-stranded DNA-binding protein 2 (SSBP2) on 5q14.1 associated with overall
      survival in combined analyses (HR, 1.64; P = 1.3 * 10(-6)). Expression of SSBP2
      in tumors from three independent data sets also was significantly related to
      patient survival (P = 5.3 * 10(-4)). Using genotype imputation, the SSBP2 SNP
      rs17296479 had the strongest statistically significant genome-wide association
      with poorer overall patient survival (HR, 1.79; 95% CI, 1.45-2.22; P = 1.0 * 10(
      7)). CONCLUSION: The minor allele of SSBP2 SNP rs17296479 and the increased tumor
      expression of SSBP2 were statistically significantly associated with poorer
      overall survival among glioblastoma patients. With further confirmation,
      previously unrecognized inherited variations influencing survival may warrant
      inclusion in clinical trials to improve randomization. Unaccounted for genetic
      influence on survival could produce unwanted bias in such studies.

PMID- 22472175
TI  - Aberrant l1 cell adhesion molecule affects tumor behavior and chemosensitivity in
      anaplastic thyroid carcinoma.
AB  - PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most invasive human
      cancers and has a poor prognosis. Molecular targets of ATC that determine its
      highly aggressive nature remain unidentified. This study investigated L1 cell
      adhesion molecule (L1CAM) expression and its role in tumorigenesis of ATCs.
      EXPERIMENTAL DESIGN: Expression of L1CAM in thyroid cancer was evaluated by
      immunohistochemical analyses of tumor samples from patients with thyroid cancer.
      We investigated the role of L1CAM in proliferation, migration, invasion, and
      chemoresistance using short hairpin RNA (shRNA) knockdown experiments in human
      ATC cell lines. Finally, we evaluated the role of L1CAM on tumorigenesis with ATC
      xenograft assay in a nude mouse model. RESULTS: L1CAM expression was not
      detectable in normal follicular epithelial cells of the thyroid or in
      differentiated thyroid carcinoma. In contrast, analysis of ATC samples showed
      specifically higher expression of L1CAM in the invasive area of the tumor.
      Specific knockdown of L1CAM in the ATC cell lines, FRO and 8505C, caused a
      significant decrease in the proliferative, migratory, and invasive capabilities
      of the cells. Suppression of L1CAM expression in ATC cell lines increased
      chemosensitivity to gemcitabine or paclitaxel. Finally, in an ATC xenograft
      model, depletion of L1CAM markedly reduced tumor growth and increased the
      survival of tumor-bearing mice. CONCLUSIONS: We report that L1CAM is highly
      expressed in the samples taken from patients with ATCs. L1CAM plays an important
      role in determining tumor behavior and chemosensitivity in cell lines derived
      from ATCs. Therefore, we suggest that L1CAM may be an important therapeutic
      target in patients with ATCs.

PMID- 22472176
TI  - Increase in cholesterol predicts survival advantage in renal cell carcinoma
      patients treated with temsirolimus.
AB  - PURPOSE: Temsirolimus is an effective treatment for renal cell carcinoma. It is
      associated with increases in serum cholesterol, triglyceride, and glucose. We
      investigated whether changes of these biomarkers could predict its efficacy.
      EXPERIMENTAL DESIGN: We examined serial measurements of cholesterol,
      triglycerides, and glucose from patients randomized to IFN or temsirolimus in the
      Global Advanced Renal Cell Carcinoma Trial. Using time-dependent proportional
      hazards models, we quantified the association between changes in these biomarkers
      from baseline with overall survival (OS) and progression-free survival (PFS). We
      also assess the extent to which changes of these biomarkers predict the effects
      of temsirolimus on survival. RESULTS: Temsirolimus was associated with larger
      mean increases in cholesterol (1.02 mmol/L; P < 0.0001), triglycerides (0.32
      mmol/L; P = 0.0008), and glucose (1.28 mmol/L; P < 0.0001) compared with IFN and
      improved survival rate (OS: HR = 0.76, P = 0.02; PFS: HR = 0.70, P = 0.001).
      Cholesterol increase during study was associated with longer survival (OS: HR =
      0.77 per mmol/L, P < 0.0001; PFS: HR = 0.81 per mmol/L; P < 0.0001). Temsirolimus
      effect on cholesterol predicted its effect on survival with no additional
      survival advantage observed after adjusting for cholesterol change during study
      (OS: HR = 1.14, P = 0.37; PFS: HR = 0.88, P = 0.35). Temsirolimus effect on
      triglycerides or glucose did not predict its effect on survival, with survival
      advantage in favor of temsirolimus still observed after adjusting for these
      factors (P = 0.003 and P = 0.002). CONCLUSION: Cholesterol increase is a
      potential predictor for temsirolimus efficacy. Longer survival in patients
      treated with temsirolimus was observed in those with larger increases in
      cholesterol. Prospectively designed biomarker studies of temsirolimus or other
      mTOR inhibitors are recommended.

PMID- 22472177
TI  - Microarray analysis verifies two distinct phenotypes of glioblastomas resistant
      to antiangiogenic therapy.
AB  - PURPOSE: To identify mechanisms and mediators of resistance to antiangiogenic
      therapy in human glioblastoma. EXPERIMENTAL DESIGN: We carried out microarray
      gene expression analysis and immunohistochemistry comparing 21 recurrent
      glioblastomas progressing during antiangiogenic treatment with VEGF neutralizing
      antibody bevacizumab to paired pretreatment tumors from the same patients.
      RESULTS: Microarray analysis revealed that bevacizumab-resistant glioblastomas
      (BRG) had two clustering patterns defining subtypes that reflect radiographic
      growth patterns. Enhancing BRGs (EBRG) exhibited MRI enhancement, a long
      established criterion for glioblastoma progression, and expressed mitogen
      activated protein kinases, neural cell adhesion molecule-1 (NCAM-1), and
      aquaporin 4. Compared with their paired pretreatment tumors, EBRGs had unchanged
      vascularity and hypoxia, with increased proliferation. Nonenhancing BRGs (NBRG)
      exhibited minimal MRI enhancement but had FLAIR-bright expansion, a newer
      criterion for glioblastoma recurrence since the advent of antiangiogenic therapy,
      and expressed integrin alpha5, laminin, fibronectin1, and PDGFRbeta. NBRGs had
      less vascularity, more hypoxia, and unchanged proliferation than their paired
      pretreatment tumors. Primary NBRG cells exhibited more stellate morphology with a
      3-fold increased shape factor and were nearly 4-fold more invasive in Matrigel
      chambers than primary cells from EBRGs or bevacizumab-naive glioblastomas (P <
      0.05). CONCLUSION: Using microarray analysis, we found two resistance patterns
      during antiangiogenic therapy with distinct molecular profiles and radiographic
      growth patterns. These studies provide valuable biologic insight into the
      resistance that has limited antiangiogenic therapy to date.

PMID- 22472178
TI  - Cortical representation of animate and inanimate objects in complex natural
      scenes.
AB  - The representations of animate and inanimate objects appear to be anatomically
      and functionally dissociated in the primate brain. How much of the variation in
      object-category tuning across cortical locations can be explained in terms of the
      animate/inanimate distinction? How is the distinction between animate and
      inanimate reflected in the arrangement of object representations along the
      cortical surface? To investigate these issues we recorded BOLD activity in visual
      cortex while subjects viewed streams of natural scenes. We then constructed an
      explicit model of object-category tuning for each voxel along the cortical
      surface. We verified that these models accurately predict responses to novel
      scenes for voxels located in anterior visual areas, and that they can be used to
      accurately decode multiple objects simultaneously from novel scenes. Finally, we
      used principal components analysis to characterize the variation in object
      category tuning across voxels. Remarkably, we found that the first principal
      component reflects the distinction between animate and inanimate objects. This
      dimension accounts for between 50 and 60% of the total variation in object
      category tuning across voxels in anterior visual areas. The importance of the
      animate-inanimate distinction is further reflected in the arrangement of voxels
      on the cortical surface: voxels that prefer animate objects tend to be located
      anterior to retinotopic visual areas and are flanked by voxels that prefer
      inanimate objects. Our explicit model of object-category tuning thus explains the
      anatomical and functional dissociation of animate and inanimate objects.

PMID- 22472179
TI  - 1H dynamic nuclear polarization based on an endogenous radical.
AB  - We demonstrate a 15-fold enhancement of solid-state NMR signals via dynamic
      nuclear polarization (DNP) based on a stable, naturally occurring radical in a
      protein: the flavin mononucleotide (FMN) semiquinone of flavodoxin. The line
      width of flavodoxin's EPR signal suggests that the dominant DNP mechanism is the
      solid effect, consistent with the field-dependent DNP enhancement profile. The
      magnitude of the enhancement as well as the bulk-polarization build-up time
      constant (tau(B)) with which it develops are dependent on the isotopic
      composition of the protein. Deuteration of the protein to 85% increased the
      nuclear longitudinal relaxation time T(1n) and tau(B) by factors of five and
      seven, respectively. Slowed dissipation of polarization can explain the 2-fold
      higher maximal enhancement than that obtained in proteated protein, based on the
      endogenous semiquinone. In contrast, the long tau(B) of TOTAPOL-based DNP in
      nonglassy samples was not accompanied by a similarly important long T(1n), and in
      this case the enhancement was greatly reduced. The low concentrations of radicals
      occurring naturally in biological systems limit the magnitude of DNP enhancement
      that is attainable by this means. However, our enhancement factors of up to 15
      can nonetheless make an important difference to the feasibility of applying solid
      state NMR to biochemical systems. We speculate that DNP based on endogenous
      radicals may facilitate MAS NMR characterization of biochemical complexes and
      even organelles, and could also serve as a source of additional structural and
      physiological information.

PMID- 22472180
TI  - Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic
      ultrasound relative to surgical staging in potentially resectable lung cancer:
      results from the ASTER randomised controlled trial.
AB  - OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of
      endosonography (followed by surgical staging if endosonography was negative),
      compared with standard surgical staging alone, in patients with non-small cell
      lung cancer (NSCLC) who are otherwise candidates for surgery with curative
      intent. DESIGN: A prospective, international, open-label, randomised controlled
      study, with a trial-based economic analysis. SETTING: Four centres: Ghent
      University Hospital, Belgium; Leuven University Hospitals, Belgium; Leiden
      University Medical Centre, the Netherlands; and Papworth Hospital, UK.
      PARTICIPANTS:  INCLUSION CRITERIA: known/suspected NSCLC, with suspected
      mediastinal lymph node involvement; otherwise eligible for surgery with curative
      intent; clinically fit for endosonography and surgery; and no evidence of
      metastatic disease. EXCLUSION CRITERIA: previous lung cancer treatment;
      concurrent malignancy; uncorrected coagulopathy; and not suitable for surgical
      staging. INTERVENTIONS: Study patients were randomised to either surgical staging
      alone (n = 118) or endosonography followed by surgical staging if endosonography
      was negative (n = 123). Endosonography diagnostic strategy used endoscopic
      ultrasound-guided fine-needle aspiration combined with endobronchial ultrasound
      guided transbronchial needle aspiration, followed by surgical staging if these
      tests were negative. Patients with no evidence of mediastinal metastases or
      tumour invasion were referred for surgery with curative intent. If evidence of
      malignancy was found, patients were referred for chemoradiotherapy. MAIN OUTCOME
      MEASURES: The main clinical outcomes were sensitivity (positive diagnostic
      test/nodal involvement during any diagnostic test or thoracotomy) and negative
      predictive value (NPV) of each diagnostic strategy for the detection of N2/N3
      metastases, unnecessary thoracotomy and complication rates. The primary economic
      outcome was cost-utility of the endosonography strategy compared with surgical
      staging alone, up to 6 months after randomisation, from a UK NHS perspective.
      RESULTS: Clinical and resource-use data were available for all 241 patients, and
      complete utilities were available for 144. Sensitivity for detecting N2/N3
      metastases was 79% [41/52; 95% confidence interval (CI) 66% to 88%] for the
      surgical arm compared with 94% (62/66; 95% CI 85% to 98%) for the endosonography
      strategy (p = 0.02). Corresponding NPVs were 86% (66/77; 95% CI 76% to 92%) and
      93% (57/61; 95% CI 84% to 97%; p = 0.26). There were 21/118 (18%) unnecessary
      thoracotomies in the surgical arm compared with 9/123 (7%) in the endosonography
      arm (p = 0.02). Complications occurred in 7/118 (6%) in the surgical arm and
      6/123 (5%) in the endosonography arm (p = 0.78): one pneumothorax related to
      endosonography and 12 complications related to surgical staging. Patients in the
      endosonography arm had greater EQ-5D (European Quality of Life-5 Dimensions)
      utility at the end of staging (0.117; 95% CI 0.042 to 0.192; p = 0.003). There
      were no other significant differences in utility. The main difference in resource
      use was the number of thoracotomies: 66% patients in the surgical arm compared
      with 53% in the endosonography arm. Resource use was similar between the groups
      in all other items. The 6-month cost of the endosonography strategy was L9713
      (95% CI L7209 to L13,307) per patient versus L10,459 (L7732 to L13,890) for the
      surgical arm, mean difference L746 (95% CI -L756 to L2494). The mean difference
      in quality-adjusted life-year was 0.015 (95% CI -0.023 to 0.052) in favour of
      endosonography, so this strategy was cheaper and more effective. CONCLUSIONS:
      Endosonography (followed by surgical staging if negative) had higher sensitivity
      and NPVs, resulted in fewer unnecessary thoracotomies and better quality of life
      during staging, and was slightly more effective and less expensive than surgical
      staging alone. Future work could investigate the need for confirmatory
      mediastinoscopy following negative endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA), the diagnostic accuracy of EUS-FNA or EBUS-TBNA
      separately and the delivery of both EUS-FNA or EBUS-TBNA by suitably trained
      chest physicians. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 97311620.
      FUNDING: This project was funded by the NIHR Health Technology Assessment
      programme and will be published in full in Health Technology Assessment; Vol. 16,
      No. 18. See the HTA programme website for further project information.

PMID- 22472181
TI  - Epstein-Barr virus LMP2A signaling in statu nascendi mimics a B cell antigen
      receptor-like activation signal.
AB  - BACKGROUND: The latent membrane protein (LMP) 2A of Epstein-Barr virus (EBV) is
      expressed during different latency stages of EBV-infected B cells in which it
      triggers activation of cytoplasmic protein tyrosine kinases. Early studies
      revealed that an immunoreceptor tyrosine-based activation motif (ITAM) in the
      cytoplasmic N-terminus of LMP2A can trigger a transient increase of the cytosolic
      Ca2+ concentration similar to that observed in antigen-activated B cells when
      expressed as a chimeric transmembrane receptor. Even so, LMP2A was subsequently
      ascribed an inhibitory rather than an activating function because its expression
      seemed to partially inhibit B cell antigen receptor (BCR) signaling in EBV
      transformed B cell lines. However, the analysis of LMP2A signaling has been
      hampered by the lack of cellular model systems in which LMP2A can be studied
      without the influence of other EBV-encoded factors. RESULTS: We have reanalyzed
      LMP2A signaling using B cells in which LMP2A is expressed in an inducible manner
      in the absence of any other EBV signaling protein. This allowed us for the first
      time to monitor LMP2A signaling in statu nascendi as it occurs during the EBV
      life cycle in vivo. We show that mere expression of LMP2A not only stimulated
      protein tyrosine kinases but also induced phospholipase C-gamma2-mediated Ca2+
      oscillations followed by activation of the extracellular signal-regulated kinase
      (Erk) mitogen-activated protein kinase pathway and induction of the lytic EBV
      gene bzlf1. Furthermore, expression of the constitutively phosphorylated LMP2A
      ITAM modulated rather than inhibited BCR-induced Ca2+ mobilization. CONCLUSION:
      Our data establish that LMP2A expression has a function beyond the putative
      inhibition of the BCR by generating a ligand-independent cellular activation
      signal that may provide a molecular switch for different EBV life cycle stages
      and most probably contributes to EBV-associated lymphoproliferative disorders.

PMID- 22472182
TI  - The prognostic value of a normal oral glucose tolerance test in pregnant women
      who tested positive at screening: a validation study.
AB  - BACKGROUND: Controversies surround a diagnosis of gestational diabetes mellitus
      (GDM). The objective of this study was to evaluate the oral glucose tolerance
      test (OGTT) for the prediction of adverse gestational and perinatal outcomes in
      pregnant women with a positive screening test for diabetes mellitus and a
      negative diagnosis, i.e. a normal 3-hour OGTT. METHODS: This validation study
      evaluated 409 pregnant women who tested positive for diabetes mellitus at
      screening. Perinatal and maternal outcomes were considered. Sensitivity and
      specificity were calculated for each of the values of the OGTT as a diagnostic
      test, with the gold standard being perinatal outcome. RESULTS: The most frequent
      risk factors were obesity, arterial hypertension and advanced maternal age. The
      most common neonatal outcomes were large-for-gestational-age infants, Cesarean
      delivery and preterm birth. A fasting blood glucose level of 87 mg/dL was the
      most powerful predictor of adverse perinatal outcome. CONCLUSIONS: At the cut-off
      level adopted by the American Diabetes Association, gestational OGTT was able to
      successfully identify in which pregnant women outcome would be unfavorable.

PMID- 22472183
TI  - A diet based on multiple functional concepts improves cardiometabolic risk
      parameters in healthy subjects.
AB  - BACKGROUND: Different foods can modulate cardiometabolic risk factors in persons
      already affected by metabolic alterations. The objective of this study was to
      assess, in healthy overweight individuals, the impact of a diet combining
      multiple functional concepts on risk markers associated with cardiometabolic
      diseases (CMD). METHODS: Fourty-four healthy women and men (50-73 y.o, BMI 25-33,
      fasting glycemia <= 6.1 mmol/L) participated in a randomized crossover
      intervention comparing a multifunctional (active) diet (AD) with a control diet
      (CD) devoid of the "active" components. Each diet was consumed during 4 wk with a
      4 wk washout period. AD included the following functional concepts: low glycemic
      impact meals, antioxidant-rich foods, oily fish as source of long-chain omega-3
      fatty acids, viscous dietary fibers, soybean and whole barley kernel products,
      almonds, stanols and a probiotic strain (Lactobacillus plantarum
      Heal19/DSM15313). RESULTS: Although the aim was to improve metabolic markers
      without promoting body weight loss, minor weight reductions were observed with
      both diets (0.9-1.8 +/- 0.2%; P < 0.05). CD did not modify the metabolic
      variables measured. AD promoted significant changes in total serum cholesterol (
      26 +/- 1% vs baseline; P < 0.0001), LDL-cholesterol (-34 +/- 1%; P < 0.0001),
      triglycerides (-19 +/- 3%; P = 0.0056), LDL/HDL (-27 +/- 2%; P < 0.0001),
      apoB/apoA1 (-10 +/- 2%; P < 0.0001), HbA1c (-2 +/- 0.4%; P = 0.0013), hs-CRP (-29
      +/- 9%; P = 0.0497) and systolic blood pressure (-8 +/- 1%  P = 0.0123). The
      differences remained significant after adjustment for weight change. After AD,
      the Framingham cardiovascular risk estimate was 30 +/- 4% (P < 0.0001) lower and
      the Reynolds cardiovascular risk score, which considers CRP values, decreased by
      35 +/- 3% (P < 0.0001). CONCLUSION: The improved biomarker levels recorded in
      healthy individuals following the multifunctional regime suggest preventive
      potential of this dietary approach against CMD.

PMID- 22472184
TI  - Effect of dairy powder rehydration state on gel formation during yogurt process.
AB  - Protein fortification and solubilisation into the milk base are important
      parameters enhancing yogurt texture. In this study, the milk base prepared from
      reconstituted skim milk powder was fortified with 2% of 'aged' (1 year old) or
      'fresh' micellar casein (MC) powder. Micellar casein powders were left to
      rehydrate at 20 degrees C for different times (5 or 180, 300, 480, 900 or 1440
      min) before acidification with glucono-delta-lactone. The rehydration of the MC
      powders into milk was monitored with a granulo-morphometer equipment, thus, for
      the first time, allowing the elucidation of MC rehydration process into an opaque
      environment such as milk. Whereas the gel point was delayed proportionally to the
      powder rehydration length, the storage modulus appears unaffected. Besides, the
      gelation onset was not altered by the powder age.

PMID- 22472185
TI  - Cadmium exposure and all-cause and cardiovascular mortality in the U.S. general
      population.
AB  - BACKGROUND: Urine cadmium concentrations were associated with all-cause and
      cardiovascular mortality in men in the 1988-1994 U.S. National Health and
      Nutrition Examination Survey (NHANES) population. Since 1988, cadmium exposure
      has decreased substantially in the United States. The associations between blood
      and urine cadmium and cardiovascular disease (CVD) mortality at more recent
      levels of exposure are unknown. OBJECTIVES: We evaluated the prospective
      association of blood and urine cadmium concentrations with all-cause and CVD
      mortality in the 1999-2004 U.S. population. METHODS: We followed 8,989
      participants who were >= 20 years of age for an average of 4.8 years. Hazard
      ratios for mortality end points comparing the 80th to the 20th percentiles of
      cadmium distributions were estimated using Cox regression. RESULTS: The
      multivariable adjusted hazard ratios [95% confidence intervals (CIs)] for blood
      and urine cadmium were 1.50 (95% CI: 1.07, 2.10) and 1.52 (95% CI: 1.00, 2.29),
      respectively, for all-cause mortality, 1.69 (95% CI: 1.03, 2.77) and 1.74 (95%
      CI: 1.07, 2.83) for CVD mortality, 1.98 (95% CI: 1.11, 3.54) and 2.53 (95% CI:
      1.54, 4.16) for heart disease mortality, and 1.73 (95% CI: 0.88, 3.40) and 2.09
      (95% CI: 1.06, 4.13) for coronary heart disease mortality. The population
      attributable risks associated with the 80th percentile of the blood (0.80 MUg/L)
      and urine (0.57 MUg/g) cadmium distributions were 7.0 and 8.8%, respectively, for
      all-cause mortality and 7.5 and 9.2%, respectively, for CVD mortality.
      CONCLUSIONS: We found strongly suggestive evidence that cadmium, at substantially
      low levels of exposure, remains an important determinant of all-cause and CVD
      mortality in a representative sample of U.S. adults. Efforts to further reduce
      cadmium exposure in the population could contribute to a substantial decrease in
      CVD disease burden.

PMID- 22472186
TI  - Quantitative determination and pharmacokinetic study of the novel anti
      Parkinson's disease candidate drug FLZ in rat brain by high performance liquid
      chromatography-tandem mass spectrometry.
AB  - FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4
      hydroxyphenyl)-acrylamide) is a novel anti-Parkinson's disease candidate drug. A
      sensitive and specific high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) method was developed and validated for the
      quantification of FLZ in rat brain. Carbamazepine was selected as the internal
      standard. Sample preparation involved double liquid-liquid extraction by n-hexane
      and ethyl acetate with high extraction efficiency. The chromatographic separation
      was achieved on a Zorbax SB-C(18) column (100 mm * 2.1 mm, 3.5 MUm) with an
      isocratic elution system comprised of acetonitrile and 0.3% aqueous acetic acid
      at a flow rate of 0.3 ml/min. The elutes were detected under positive
      electrospray ionization (ESI) and the target analytes were quantified by multiple
      reaction monitoring (MRM) mode. The method was sensitive with the lowest limit of
      quantification (LLOQ) at 1.0 ng/g brain tissue. Good linearity (r>0.99) was
      obtained over the range of 1.0-400 ng/g. The intra- and inter-day precision
      ranged from 0.68% to 12%, while the accuracy between 92.7% and 111%. In addition,
      the stability, recovery and matrix effect involved in this method were also
      validated. The method was used to investigate the pharmacokinetics of FLZ in rat
      brain successfully after intravenous administration. The brain distribution
      studies showed that the brain distribution of FLZ was limited with the
      penetration ratio less than 0.1 in rats, with no target effect in the seven
      collected regions. Inhibition of P-glycoprotein (P-gp) by zosuquidar.3HCl ((2R)-1
      {4-[(1aR,10bS)-1,1-difluoro-1,1a,6,10b
      tetrahydrodibenzo[a,e]cyclopropa[c][7]annulen-6-yl]-1-piperazinyl}-3-(5
      quinolinyloxy)-2-propanol trihydrochloride) resulted in a significant increase in
      brain-to-plasma ratio, while no significant increase by inhibition of breast
      cancer resistance protein (BCRP) by ko143 (2-methyl-2-propanyl 3-[(3S,6S,12aS)-6
      isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a
      octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-3-yl]propanoate). The results
      indicated that FLZ had poor penetration to the brain due to the P-gp transport
      system.

PMID- 22472188
TI  - Electrical, molecular and behavioral effects of interictal spiking in the rat.
AB  - OBJECTIVE: Epilepsy is a disease characterized by chronic seizures, but is
      associated with significant comorbidities between seizures including cognitive
      impairments, hyperactivity, and depression. To study this interictal state, we
      characterized the electrical, molecular, and behavior effects of chronic,
      neocortical interictal spiking in rats. METHODS: A single injection of tetanus
      toxin into somatosensory cortex generated chronic interictal spiking measured by
      long-term video EEG monitoring and was correlated with motor activity. The
      cortical pattern of biomarker activation and the effects of blocking MAPK
      signaling on interictal spiking and behavior were determined. RESULTS: Interictal
      spiking in this model increases in frequency, size, and becomes repetitive over
      time, but is rarely associated with seizures. Interictal spiking was sufficient
      to produce the same molecular and cellular pattern of layer 2/3-specific CREB
      activation and plasticity gene induction as is seen in the human interictal
      state. Increasing spike frequency was associated with hyperactivity, demonstrated
      by increased ambulatory activity and preferential circling toward the spiking
      hemisphere. Loud noises induced epileptic discharges, identical to spontaneous
      discharges. Treatment with a selective MAPK inhibitor prevented layer 2/3 CREB
      activation, reduced the frequency of epileptic discharges, and normalized
      behavioral abnormalities, but had no effect on seizures induced by electrical
      kindling. INTERPRETATION: These results provide insights into the development of
      interictal epileptic spiking, their relationship to behavior, and suggest that
      interictal and ictal activities utilize distinct molecular pathways. This model,
      that parallels recent observations in humans, will be useful to develop
      therapeutics against interictal spiking and its behavioral comorbidities.

PMID- 22472189
TI  - Generation of a novel rodent model for DYT1 dystonia.
AB  - A mutation in the coding region of the Tor1A gene, resulting in a deletion of a
      glutamic acid residue in the torsinA protein (?ETorA), is the major cause of the
      inherited autosomal-dominant early onset torsion dystonia (DYT1). The
      pathophysiological consequences of this amino acid loss are still not understood.
      Currently available animal models for DYT1 dystonia provided important insights
      into the disease; however, they differ with respect to key features of torsinA
      associated pathology. We developed transgenic rat models harboring the full
      length human mutant and wildtype Tor1A gene. A complex phenotyping approach
      including classical behavioral tests, electrophysiology and neuropathology
      revealed a progressive neurological phenotype in ?ETorA expressing rats.
      Furthermore, we were able to replicate key pathological features of torsinA
      associated pathology in a second species, such as nuclear envelope pathology,
      behavioral abnormalities and plasticity changes. We therefore suggest that this
      rat model represents an appropriate new model suitable to further investigate the
      pathophysiology of ?ETorA and to test for therapeutic approaches.

PMID- 22472187
TI  - The group 2 metabotropic glutamate receptor agonist LY379268 rescues neuronal,
      neurochemical and motor abnormalities in R6/2 Huntington's disease mice.
AB  - Excitotoxic injury to striatum by dysfunctional cortical input or aberrant
      glutamate uptake may contribute to Huntington's disease (HD) pathogenesis. Since
      corticostriatal terminals possess mGluR2/3 autoreceptors, whose activation
      dampens glutamate release, we tested the ability of the mGluR2/3 agonist LY379268
      to improve the phenotype in R6/2 HD mice with 120-125 CAG repeats. Daily
      subcutaneous injection of a maximum tolerated dose (MTD) of LY379268 (20mg/kg)
      had no evident adverse effects in WT mice, and diverse benefits in R6/2 mice,
      both in a cohort of mice tested behaviorally until the end of R6/2 lifespan and
      in a cohort sacrificed at 10weeks of age for blinded histological analysis. MTD
      LY379268 yielded a significant 11% increase in R6/2 survival, an improvement on
      rotarod, normalization and/or improvement in locomotor parameters measured in
      open field (activity, speed, acceleration, endurance, and gait), a rescue of a 15
      20% cortical and striatal neuron loss, normalization of SP striatal neuron
      neurochemistry, and to a lesser extent enkephalinergic striatal neuron
      neurochemistry. Deficits were greater in male than female R6/2 mice, and drug
      benefit tended to be greater in males. The improvements in SP striatal neurons,
      which facilitate movement, are consistent with the improved movement in LY379268
      treated R6/2 mice. Our data indicate that mGluR2/3 agonists may be particularly
      useful for ameliorating the morphological, neurochemical and motor defects
      observed in HD.

PMID- 22472190
TI  - Validated spectrophotometric methods for determination of Alendronate sodium in
      tablets through nucleophilic aromatic substitution reactions.
AB  - BACKGROUND: Alendronate (ALD) is a member of the bisphosphonate family which is
      used for the treatment of osteoporosis, bone metastasis, Paget's disease,
      hypocalcaemia associated with malignancy and other conditions that feature bone
      fragility. ALD is a non-chromophoric compound so its determination by
      conventional spectrophotometric methods is not possible. So two derivatization
      reactions were proposed for determination of ALD through the reaction with 4
      chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene
      (DNFB) as chromogenic derivatizing reagents. RESULTS: Three simple and sensitive
      spectrophotometric methods are described for the determination of ALD. Method I
      is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed
      derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed
      reaction of the studied drug with DNFB at room temperature. The reactions
      products were measured at 472, 378 and 374 nm, for methods I, II and III,
      respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0,
      4.0-40.0 and 1.5-30.0 MUg/mL with lower limits of detection of 0.09, 1.06 and
      0.06 MUg/mL for Methods I, II and III, respectively. The proposed methods were
      applied for quantitation of the studied drug in its pure form with mean
      percentage recoveries of 100.47 +/- 1.12, 100.17 +/- 1.21 and 99.23 +/- 1.26 for
      Methods I, II and III, respectively. Moreover the proposed methods were
      successfully applied for determination of ALD in different tablets. Proposals of
      the reactions pathways have been postulated. CONCLUSION: The proposed
      spectrophotometric methods provided sensitive, specific and inexpensive
      analytical procedures for determination of the non-chromophoric drug alendronate
      either per se or in its tablet dosage forms without interference from common
      excipients. GRAPHICAL

PMID- 22472191
TI  - Development and evaluation of social cognitive measures related to adolescent
      dietary behaviors.
AB  - BACKGROUND: This study aimed to develop and evaluate the reliability and
      factorial validity, of social-cognitive measures related to adolescent healthy
      eating behaviors. METHODS: A questionnaire was developed based on constructs from
      Bandura's Social Cognitive Theory and included the following scales: self
      efficacy, intentions (proximal goals), situation (perceived environment), social
      support, behavioral strategies, outcome expectations and expectancies. The
      questionnaire was administered with a two week test-retest among secondary school
      students (n = 173, age = 13.72 +/- 1.24). Confirmatory factor analysis was
      employed to examine model-fit for each scale using multiple indices including:
      chi-square index, comparative-fit index (CFI), goodness-of-fit index (GFI), and
      the root mean square error of approximation (RMSEA). Reliability properties were
      also examined (ICC and Cronbach's alpha). RESULTS: The reliability and factorial
      validity of each scale is supported: fit indices suggest each model to be an
      adequate-to-exact fit to the data; internal consistency was acceptable-to-good
      (alpha = 0.65-0.79); rank order repeatability was strong (ICC = 0.81-0.89).
      CONCLUSIONS AND IMPLICATIONS: Results support the reliability and factorial
      validity of social cognitive scales relating to healthy eating behaviors among
      adolescents. As such, the developed scales have utility for identifying potential
      social cognitive correlates of adolescent dietary behavior, mediators of dietary
      behavior change and validity testing of theoretical models based on Social
      Cognitive Theory.

PMID- 22472192
TI  - Analysis of leukemia-specific aneuploidies in cultured myeloid progenitor cells
      in the absence and presence of formaldehyde exposure.
AB  - A recently published human study suggested that exposure to formaldehyde (FA) at
      the workplace might induce leukemia-specific aneuploidies (monosomy 7 and trisomy
      8) in cultured myeloid progenitor cells. Despite its preliminary character, this
      study was considered by the International Agency for Research on Cancer to be a
      potential mechanistic explanation for the induction of leukemia by FA. To further
      evaluate the reliability of these findings, chromosome preparations from cultured
      myeloid progenitor cells (obtained from blood samples of five healthy subjects)
      were analyzed by fluorescence in situ hybridization (FISH) for spontaneously
      occurring numerical aberrations after cultivation for 9 days. FISH analysis with
      probes for chromosomes 6, 7, and 8 revealed that the baseline frequency of
      aneuploid metaphases is similar and rather low for all three chromosomes tested.
      More monosomies than trisomies were measured. We also exposed myeloid progenitor
      cells during the whole cultivation period to FA and determined the frequency of
      aneuploidies after 9 days of cultivation. The results clearly indicate that FA
      did not induce aneuploidy under these experimental conditions. In contrast,
      aneuploidy was induced under these conditions by the known aneugen vincristine.
      Myeloid progenitor cells from healthy subjects were not particularly sensitive
      toward the cytotoxic action of FA. Colony forming ability in the presence of FA
      was not reduced to a higher degree than in cultured cell lines (A549; V79). Our
      results do not support the assumption of a specific effect of FA on myeloid
      progenitor cells as a potential mechanism for the induction of leukemia.

PMID- 22472193
TI  - Prognosis and prognostic factors of papillary thyroid carcinoma in patients under
      20 years.
AB  - Age is an important prognostic factor of papillary thyroid carcinoma (PTC).  In
      this study, we investigated the prognosis and prognostic factors of PTC in
      patients younger than 20 years.  We enrolled 110 patients who underwent initial
      surgery at Kuma Hospital between 1987 and 2008. Tumor size > 4 cm, metastatic
      node >= 3 cm, and significant extrathyroid extension were more frequently
      detected in 8 patients with distant metastasis at diagnosis than in 102 patients
      without distant metastasis.  Ten- and 20-year lymph node recurrence-free survival
      (LN-RFS) and distant recurrence-free survival (DRFS) rates were 84 and 80%, and
      95 and 89%, respectively.  Metastatic node >= 3 cm, age <= 16 years, tumor size >
      4 cm, and male gender affected LN-RFS, and the former two had an independent
      prognostic value in multivariate analysis.  Metastastic node >= 3 cm, significant
      extrathyroid extension, age <= 16 years, tumor size > 4 cm, and a male gender
      predicted a poor DRFS, and the former two were independent prognostic factors. 
      To date, only 2 patients have died of PTC.  These findings suggest that, in the
      subset of PTC patients younger than 20 years, metastatic node >= 3 cm,
      significant extension, and age <= 16 were important signs of aggressiveness of
      carcinoma, and careful treatment is necessary for patients with these
      characteristics, although the cause-specific survival was excellent.

PMID- 22472194
TI  - The mechanism of pleural inflammation by long carbon nanotubes: interaction of
      long fibres with macrophages stimulates them to amplify pro-inflammatory
      responses in mesothelial cells.
AB  - Carbon nanotubes (CNT) are high aspect ratio nanoparticles with diameters in the
      nanometre range but lengths extending up to hundreds of microns. The structural
      similarities between CNT and asbestos have raised concern that they may pose a
      similar inhalation hazard. Recently CNT have been shown to elicit a length
      dependent, asbestos-like inflammatory response in the pleural cavity of mice,
      where long fibres caused inflammation but short fibres did not. However the
      cellular mechanisms governing this response have yet to be elucidated. This study
      examined the in vitro effects of a range of CNT for their ability to stimulate
      the release of the acute phase cytokines; IL-1beta, TNFalpha, IL-6 and the
      chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results
      showed that direct exposure to CNT resulted in significant cytokine release from
      the macrophages but not mesothelial cells. This pro-inflammatory response was
      length dependent but modest and was shown to be a result of frustrated
      phagocytosis. Furthermore the indirect actions of the CNT were examined by
      treating the mesothelial cells with conditioned media from CNT-treated
      macrophages. This resulted in a dramatic amplification of the cytokine release
      from the mesothelial cells, a response which could be attenuated by inhibition of
      phagocytosis during the initial macrophage CNT treatments. We therefore
      hypothesise that long fibres elicit an inflammatory response in the pleural
      cavity via frustrated phagocytosis in pleural macrophages. The activated
      macrophages then stimulate an amplified pro-inflammatory cytokine response from
      the adjacent pleural mesothelial cells. This mechanism for producing a pro
      inflammatory environment in the pleural space exposed to long CNT has
      implications for the general understanding of fibre-related pleural disease and
      design of safe nanofibres.

PMID- 22472195
TI  - Evidence of novel fine-scale structural variation at autism spectrum disorder
      candidate loci.
AB  - BACKGROUND: Autism spectrum disorders (ASD) represent a group of
      neurodevelopmental disorders characterized by a core set of social-communicative
      and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major
      inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors
      (GABR). Multiple lines of evidence, including altered GABA and GABA receptor
      expression in autistic patients, indicate that the GABAergic system may be
      involved in the etiology of autism. METHODS: As copy number variations (CNVs),
      particularly rare and de novo CNVs, have now been implicated in ASD risk, we
      examined the GABA receptors and genes in related pathways for structural
      variation that may be associated with autism. We further extended our candidate
      gene set to include 19 genes and regions that had either been directly implicated
      in the autism literature or were directly related (via function or ancestry) to
      these primary candidates. For the high resolution CNV screen we employed custom
      designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our
      probes spanned a total of 11 Mb of GABA-related and additional candidate regions
      with a density of approximately one probe every 200 nucleotides, allowing a
      theoretical resolution for detection of CNVs of approximately 1 kb or greater on
      average. One hundred and sixty-eight autism cases and 149 control individuals
      were screened for structural variants. Prioritized CNV events were confirmed
      using quantitative PCR, and confirmed loci were evaluated on an additional set of
      170 cases and 170 control individuals that were not included in the original
      discovery set. Loci that remained interesting were subsequently screened via
      quantitative PCR on an additional set of 755 cases and 1,809 unaffected family
      members. RESULTS: Results include rare deletions in autistic individuals at
      JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion
      polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall,
      statistically significant enrichment in affected vs. unaffected individuals was
      observed for NRXN1 deletions. CONCLUSIONS: These results provide additional
      support for the role of rare structural variation in ASD.

PMID- 22472197
TI  - Survival and metabolic activity of lux-marked Escherichia coli O157:H7 in
      different types of milk.
AB  - Escherichia coli O157:H7 is a potentially lethal pathogen which has been
      responsible for several outbreaks of milk-borne illness in recent years. The
      objective of this study was to evaluate the survival and metabolic activity
      (indexed by bioluminescence) of a chromosomally lux-marked strain of Esch. coli
      O157:H7 in raw, pasteurized and microfiltered pasteurized milk at 4 and 20
      degrees C for up to 14 d. Results showed that the population of Esch. coli
      O157:H7 and its metabolic activity decreased in all samples during storage at 4
      degrees C, with no significant differences in numbers observed between the
      different milk types; but metabolic activity was significantly higher (P<0.05) in
      the microfiltered pasteurized milk than that in raw milk. At 20 degrees C, Esch.
      coli O157:H7 counts and cell activity peaked at day 2, and then declined
      progressively. At 20 degrees C, survival and metabolic activity were
      significantly lower in raw milk compared with pasteurized milk. We conclude that
      storage temperature is more important in regulating the survival of Esch. coli
      O157 in contaminated milk than its origin/pre-treatment conditions.

PMID- 22472196
TI  - Arsenic-transformed malignant prostate epithelia can convert noncontiguous normal
      stem cells into an oncogenic phenotype.
AB  - BACKGROUND: Cancer stem cells (CSCs) are likely critical to carcinogenesis, and,
      like normal stem cells (NSCs), are affected by microenvironmental factors.
      Malignant cells release extracellular factors, modifying tumor behavior.
      Inorganic arsenic, a human carcinogen, is associated with an overproduction of
      CSCs in various model systems of carcinogenesis. OBJECTIVE: We aimed to determine
      if NSCs are influenced by nearby arsenic-transformed malignant epithelial cells
      (MECs) as a possible factor in arsenic-associated CSC overabundance. METHODS:
      Transwell noncontact co-culture allowed the study of the effects of non
      contiguous, arsenic-transformed prostate MECs on the isogenic human prostate NSC
      line, WPE-stem. Cancer phenotype was assessed by evaluating secreted matrix
      metalloproteinases (MMPs), invasiveness, colony formation, and spheroid
      formation. Gene expression was assessed at the protein (Western blot) or mRNA
      (real-time reverse transcription-polymerase chain reaction) levels. RESULTS:
      Noncontact co-culture of MECs and NSCs rapidly (<= 3 weeks) caused hypersecretion
      of MMPs and marked suppression of the tumor suppressor gene PTEN in NSCs. NSCs co
      cultured with MECs also showed increased invasiveness and clonogenicity and
      formed more free-floating spheroids and highly branched ductal-like structures in
      Matrigel, all typical for CSCs. MEC co-culture caused dysregulated self-renewal
      and differentiation-related gene expression patterns and epithelial-to
      mesenchymal transition in NSCs consistent with an acquired cancer phenotype.
      Interleukin-6 (IL-6), a cytokine involved in tumor microenvironment control, was
      hypersecreted by MECs, and IL-6 exposure of NSCs resulted in the duplication of
      several responses in NSCs of conversion to CSCs via MEC co-culture (e.g., MMP
      hypersecretion, decreased PTEN). CONCLUSIONS: Arsenic-transformed MECs recruit
      nearby NSCs into a cancer phenotype, thereby potentially increasing CSC number.
      This may be a factor in arsenic-induced CSC overabundance seen in multiple model
      systems.

PMID- 22472198
TI  - Trailblazing healthcare: institutionalizing and integrating complementary
      medicine.
AB  - OBJECTIVES: This study examines three integrative health centers to understand
      their (1) historical development, organizational goals, and modalities, (2) the
      processes and challenges of integrating complementary and allopathic medicine,
      while encouraging staff collaboration, and (3) how each center becomes
      institutionalized within their community. METHODS: We focus on three
      organizational case studies that reflect varying forms of integrative health care
      practices in three U.S. cities. Participant-observation and in-depth interviews
      with center directors were analyzed qualitatively. RESULTS: Important patterns
      found within the three cases are (1) the critical role of visionary biomedical
      practitioners who bridge complementary and allopathic practices, (2)
      communicating integration internally through team interaction, and (3)
      communicating integration externally through spatial location, naming, and
      community outreach. CONCLUSION: IM centers continue to blaze new trails toward
      mainstream access and acceptance by gathering evidence for IM, encouraging team
      collaboration within organizational contexts, constructing organizational
      identity, and negotiating insurance reimbursements. PRACTICE IMPLICATIONS: IM is
      not the enactment of specific modalities, but rather a philosophy of healing.
      Though scheduling conflicts, skepticism, and insurance coverage may be obstacles
      toward IM, collaboration among specialists and with patients should be the
      ultimate goal.

PMID- 22472199
TI  - Digital clubbing following upper limb neurovascular injury.

PMID- 22472200
TI  - Treatment of neglected divergent dislocation of hamatometacarpal complex with a
      circular spider plate.

PMID- 22472201
TI  - Significant improvement in islet yield and survival with modified ET-Kyoto
      solution: ET-Kyoto/Neutrophil elastase inhibitor.
AB  - Although islet transplantation can achieve insulin independence in patients with
      type 1 diabetes, sufficient number of islets derived from two or more donors is
      usually required to achieve normoglycemia. Activated neutrophils and neutrophil
      elastase (NE), which is released from these neutrophils, can directly cause
      injury in islet grafts. We hypothesized that inhibition of NE improves islet
      isolation and islet allograft survival. We tested our hypothesis by examining the
      effects of modified ET-Kyoto solution supplemented with sivelestat, a NE
      inhibitor (S-Kyoto solution), on islet yield and viability in islet isolation and
      the effect of intraperitoneally injected sivelestat on islet graft survival in a
      mouse allotransplant model. NE and proinflammatory cytokines such as tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-6 increased markedly at the end
      of warm digestion during islet isolation and exhibited direct cytotoxic activity
      against the islets causing their apoptosis. The use of S-Kyoto solution
      significantly improved islet yield and viability. Furthermore, treatment with
      sivelestat resulted in significant prolongation of islet allograft survival in
      recipient mice. Furthermore, serum levels of IL-6 and TNF-alpha at 1 and 2 weeks
      posttransplantation were significantly higher in islet recipients than before
      transplantation. Our results indicated that NE released from activated
      neutrophils negatively affects islet survival and that its suppression both in
      vitro and in vivo improved islet yield and prolonged islet graft survival. The
      results suggest that inhibition of NE activity could be potentially useful in
      islet transplantation for patients with type 1 diabetes mellitus.

PMID- 22472202
TI  - Conscious and unconscious thought in artificial grammar learning.
AB  - Unconscious Thought Theory posits that a period of distraction after information
      acquisition leads to unconscious processing which enhances decision making
      relative to conscious deliberation or immediate choice (Dijksterhuis, 2004).
      Support thus far has been mixed. In the present study, artificial grammar
      learning was used in order to produce measurable amounts of conscious and
      unconscious knowledge. Intermediate phases were introduced between training and
      testing. Participants engaged in conscious deliberation of grammar rules, were
      distracted for the same period of time, or progressed immediately from training
      to testing. No differences in accuracy were found between intermediate phase
      groups acting on decisions made with meta-cognitive awareness (either feeling
      based intuitive responding or conscious rule- or recollection-based responding).
      However, the accuracy of guess responses was significantly higher after
      distraction relative to immediate progression or conscious deliberation. The
      results suggest any beneficial effects of 'unconscious thought' may not always
      transfer to conscious awareness.

PMID- 22472203
TI  - On capturing the essence of self-generated action: a reply to Obhi (2012).

PMID- 22472204
TI  - The T3-induced gene KLF9 regulates oligodendrocyte differentiation and myelin
      regeneration.
AB  - Hypothyroidism is a well-described cause of hypomyelination. In addition, thyroid
      hormone (T3) has recently been shown to enhance remyelination in various animal
      models of CNS demyelination. What are the ways in which T3 promotes the
      development and regeneration of healthy myelin? To begin to understand the
      mechanisms by which T3 drives myelination, we have identified genes regulated
      specifically by T3 in purified oligodendrocyte precursor cells (OPCs). Among the
      genes identified by genomic expression analyses were four transcription factors,
      Kruppel-like factor 9 (KLF9), basic helix-loop-helix family member e22 (BHLHe22),
      Hairless (Hr), and Albumin D box-binding protein (DBP), all of which were induced
      in OPCs by both brief and long term exposure to T3. To begin to investigate the
      role of these genes in myelination, we focused on the most rapidly and robustly
      induced of these, KLF9, and found it is both necessary and sufficient to promote
      oligodendrocyte differentiation in vitro. Surprisingly, we found that loss of
      KLF9 in vivo negligibly affects the formation of CNS myelin during development,
      but does significantly delay remyelination in cuprizone-induced demyelinated
      lesions. These experiments indicate that KLF9 is likely a novel integral
      component of the T3-driven signaling cascade that promotes the regeneration of
      lost myelin. Future analyses of the roles of KLF9 and other identified T3-induced
      genes in myelination may lead to novel insights into how to enhance the
      regeneration of myelin in demyelinating diseases such as multiple sclerosis.

PMID- 22472205
TI  - Sorption of phosphate onto mesoporous gamma-alumina studied with in-situ ATR-FTIR
      spectroscopy.
AB  - BACKGROUND: Due to the extensive use of phosphates in industry, agriculture and
      households, the phosphate - gamma-alumina interactions are important for
      understanding its detrimental contribution to eutrophication in lakes and rivers.
      In situ Fourier transform infrared (FTIR) spectroscopy can provide more detailed
      information on the adsorbate-adsorbent interaction and the formation of hydrogen
      bonds. RESULTS: In situ ATR-FTIR spectroscopy was used to identify phosphate
      complexes adsorbed within the three-dimensional network of mesoporous gamma
      alumina at pH 4.1 and 9.0. The integrated intensity between 850 cm-1 and 1250 cm
      1 was used as a relative measure of the amount of adsorbed phosphate. The
      integrated intensity proved to be about 3 times higher at pH 4.1 as compared with
      the corresponding intensity at pH 9.0. The adsorption of phosphate at the two pH
      conditions could be well described by the Langmuir adsorption isotherm at low
      concentrations and the empirical Freundlich adsorption isotherm for the whole
      concentration range, viz. 5 - 2000 MUM. CONCLUSIONS: From the band shape of
      infrared spectra at pH 4.1 and pH 9.0, it was proposed that the symmetry of the
      inner-sphere surface complex formed between phosphate and gamma-alumina was C1 at
      the lower pH value, whilst the higher value (9.0) implied a surface complex with
      C2v or C1 symmetry. The difference in adsorbed amount of phosphate at the two pH
      values was ascribed to the reduced fraction of = AlOH2+ surface sites and the
      increased fraction of = AlO- sites upon increasing pH from 4 to 9.

PMID- 22472206
TI  - The foodscape: classification and field validation of secondary data sources
      across urban/rural and socio-economic classifications in England.
AB  - BACKGROUND: In recent years, alongside the exponential increase in the prevalence
      of overweight and obesity, there has been a change in the food environment
      (foodscape). This research focuses on methods used to measure and classify the
      foodscape. This paper describes the foodscape across urban/rural and socio
      economic divides. It examines the validity of a database of food outlets obtained
      from Local Authority sources (secondary level & desk based), across urban/rural
      and socio-economic divides by conducting fieldwork (ground-truthing).
      Additionally this paper tests the efficacy of using a desk based classification
      system to describe food outlets, compared with ground-truthing. METHODS: Six
      geographically defined study areas were purposively selected within North East
      England consisting of two Lower Super Output Areas (LSOAs; a small administrative
      geography) each. Lists of food outlets were obtained from relevant Local
      Authorities (secondary level & desk based) and fieldwork (ground-truthing) was
      conducted. Food outlets were classified using an existing tool. Positive
      predictive values (PPVs) and sensitivity analysis was conducted to explore
      validation of secondary data sources. Agreement between 'desk' and 'field' based
      classifications of food outlets were assessed. RESULTS: There were 438 food
      outlets within all study areas; the urban low socio-economic status (SES) area
      had the highest number of total outlets (n = 210) and the rural high SES area had
      the least (n = 19). Differences in the types of outlets across areas were
      observed. Comparing the Local Authority list to fieldwork across the geographical
      areas resulted in a range of PPV values obtained; with the highest in urban low
      SES areas (87%) and the lowest in Rural mixed SES (79%). While sensitivity ranged
      from 95% in the rural mixed SES area to 60% in the rural low SES area. There were
      no significant associations between field/desk percentage agreements across any
      of the divides. CONCLUSION: Despite the relatively small number of areas, this
      work furthers our understanding of the validity of using secondary data sources
      to identify and classify the foodscape in a variety of geographical settings.
      While classification of the foodscape using secondary Local Authority food outlet
      data with information obtained from the internet, is not without its
      difficulties, desk based classification would be an acceptable alternative to
      fieldwork, although it should be used with caution.

PMID- 22472207
TI  - Fertile forests produce biomass more efficiently.
AB  - Trees with sufficient nutrition are known to allocate carbon preferentially to
      aboveground plant parts. Our global study of 49 forests revealed an even more
      fundamental carbon allocation response to nutrient availability: forests with
      high-nutrient availability use 58 +/- 3% (mean +/- SE; 17 forests) of their
      photosynthates for plant biomass production (BP), while forests with low-nutrient
      availability only convert 42 +/- 2% (mean +/- SE; 19 forests) of annual
      photosynthates to biomass. This nutrient effect largely overshadows previously
      observed differences in carbon allocation patterns among climate zones, forest
      types and age classes. If forests with low-nutrient availability use 16 +/- 4%
      less of their photosynthates for plant growth, what are these used for? Current
      knowledge suggests that lower BP per unit photosynthesis in forests with low-
      versus forests with high-nutrient availability reflects not merely an increase in
      plant respiration, but likely results from reduced carbon allocation to
      unaccounted components of net primary production, particularly root symbionts.

PMID- 22472208
TI  - Enhanced excitability of small dorsal root ganglion neurons in rats with bone
      cancer pain.
AB  - BACKGROUND: Primary and metastatic cancers that affect bone are frequently
      associated with severe and intractable pain. The mechanisms underlying the
      development of bone cancer pain are largely unknown. The aim of this study was to
      determine whether enhanced excitability of primary sensory neurons contributed to
      peripheral sensitization and tumor-induced hyperalgesia during cancer condition.
      In this study, using techniques of whole-cell patch-clamp recording associated
      with immunofluorescent staining, single-cell reverse-transcriptase PCR and
      behavioral test, we investigated whether the intrinsic membrane properties and
      the excitability of small-sized dorsal root ganglion (DRG) neurons altered in a
      rat model of bone cancer pain, and whether suppression of DRG neurons activity
      inhibited the bone cancer-induced pain. RESULTS: Our present study showed that
      implantation of MRMT-1 tumor cells into the tibial canal in rats produced
      significant mechanical and thermal hyperalgesia in the ipsilateral hind paw.
      Moreover, implantation of tumor cells provoked spontaneous discharges and tonic
      excitatory discharges evoked by a depolarizing current pulse in small-sized DRG
      neurons. In line with these findings, alterations in intrinsic membrane
      properties that reflect the enhanced neuronal excitability were observed in small
      DRG neurons in bone cancer rats, of which including: 1) depolarized resting
      membrane potential (RMP); 2) decreased input resistance (Rin); 3) a marked
      reduction in current threshold (CT) and voltage threshold (TP) of action
      potential (AP); 4) a dramatic decrease in amplitude, overshot, and duration of
      evoked action potentials as well as in amplitude and duration of
      afterhyperpolarization (AHP); and 5) a significant increase in the firing
      frequency of evoked action potentials. Here, the decreased AP threshold and
      increased firing frequency of evoked action potentials implicate the occurrence
      of hyperexcitability in small-sized DRG neurons in bone cancer rats. In
      addiotion, immunofluorescent staining and single-cell reverse-transcriptase PCR
      revealed that in isolated small DRG neurons, most neurons were IB4-positive, or
      expressed TRPV1 or CGRP, indicating that most recorded small DRG neurons were
      nociceptive neurons. Finally, using in vivo behavioral test, we found that
      blockade of DRG neurons activity by TTX inhibited the tumor-evoked mechanical
      allodynia and thermal hyperalgesia in bone cancer rats, implicating that the
      enhanced excitability of primary sensory neurons underlied the development of
      bone cancer pain. CONCLUSIONS: Our present results suggest that implantation of
      tumor cells into the tibial canal in rats induces an enhanced excitability of
      small-sized DRG neurons that is probably as results of alterations in intrinsic
      electrogenic properties of these neurons. Therefore, alterations in intrinsic
      membrane properties associated with the hyperexcitability of primary sensory
      neurons likely contribute to the peripheral sensitization and tumor-induced
      hyperalgesia under cancer condition.

PMID- 22472209
TI  - Fracture risk in living kidney donors: a matched cohort study.
AB  - BACKGROUND: Chronic kidney disease increases the risk of bone fragility fractures
      (osteoporotic fractures). Living kidney donors lose 50% of their renal mass and
      show changes in calcium homeostasis. We studied whether living kidney donation
      increases the risk of fragility fracture. DESIGN: Retrospective matched-cohort
      study. SETTING & PARTICIPANTS: We reviewed the medical charts of all 2,015 adults
      in Ontario, Canada, who donated a kidney between 1992 and 2009 (surgeries
      performed across 5 transplant programs). We linked this information to health
      care databases and randomly selected 20,150 matched nondonors from the healthiest
      portion of the general population. Median age was 43 (95% CI, 24-50) years at
      study enrollment. Donors and nondonors were then followed up for a median of 6.6
      years and a maximum of 17.7 years. PREDICTOR: Living donor nephrectomy. OUTCOMES:
      The primary outcome was lower- and upper-extremity fragility fractures.
      Individuals who reached 66 years or older in follow-up had bisphosphonate
      prescriptions recorded. RESULTS: The rate of fragility fracture was no higher in
      donors compared with nondonors (16.4 vs 18.7 events/10,000 person-years; rate
      ratio, 0.88; 95% CI, 0.58-1.32). Results were similar in multiple additional
      analyses. There was little difference in the proportion of older adults in follow
      up who received a bisphosphonate prescription (17.1% vs 15.2%; P = 0.4).
      LIMITATIONS: These are interim results. Ongoing surveillance of this and other
      donor cohorts is warranted to be sure an association does not manifest with
      longer follow-up. CONCLUSIONS: To date, there is no evidence of increased
      fragility fracture risk in living kidney donors. Our results meet an information
      need and are reassuring for the safety of the practice.

PMID- 22472210
TI  - Effects of decabrominated diphenyl ether (PBDE-209) in regulation of growth and
      apoptosis of breast, ovarian, and cervical cancer cells.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs), commonly used in building
      materials, electronics, plastics, polyurethane foams, and textiles, are health
      hazards found in the environment. OBJECTIVE: In this study we investigated the
      effects of PBDE-209, a deca-PBDE, on the regulation of growth and apoptosis of
      breast, ovarian, and cervical cancer cells as well as the underlying protein
      alterations. METHODS: We used MCF-7 and MCF-7/ADR (multidrug-resistant MCF-7)
      breast cancer cell lines, the HeLa cervical cancer cell line, the OVCAR-3 ovarian
      cancer cell line, and the normal CHO (Chinese hamster ovary) cell line to assess
      the effects of PBDE-209 using cell viability, immunofluorescence, and flow
      cytometric assays. Western blot assays were used to detect changes in protein
      expression. To assess the effects of PBDE-209 on apoptosis, we used the protein
      kinase Calpha (PKCalpha) inhibitor Go 6976, the extracellular signal-regulated
      kinase (ERK) inhibitor PD98059, and tamoxifen. RESULTS: Our data indicate that
      PBDE-209 increased viability and proliferation of the tumor cell lines and in CHO
      cells in a dose- and time-dependent manner. PBDE-209 also altered cell cycle
      distribution by inducing the S phase or G2/M phase. Furthermore, PBDE-209
      partially suppressed tamoxifen-induced cell apoptosis in the breast cancer cell
      lines (MCF-7 and MCF-7/ADR) but suppressed Go 6976- and PD98059-induced apoptosis
      in all cell lines. At the molecular level, PBDE-209 enhanced PKCalpha and ERK1/2
      phosphorylation in the cell lines. CONCLUSIONS: Our data demonstrate that PBDE
      209 is able to promote proliferation of various cancer cells from the female
      reproductive system and normal ovarian CHO cells. Furthermore, it reduced
      tamoxifen, PKCalpha, and ERK inhibition-induced apoptosis. Finally, PBDE-209 up
      regulated phosphorylation of PKCalpha and ERK1/2 proteins in tumor cells and in
      CHO cells.

PMID- 22472211
TI  - Morusinol extracted from Morus alba inhibits arterial thrombosis and modulates
      platelet activation for the treatment of cardiovascular disease.
AB  - Morus alba (white mulberry) has been used in traditional Chinese medicine as an
      anti-headache, diuretic, expectorant, and anti-diabetic agent. In previous
      studies, extracts of Morus alba demonstrated favorable biological properties,
      such as antioxidant activity, suppression of lipoxygenase (LOX)-1, cytotoxicity
      against cancer cells, and inhibition of the invasion and migration of cancer
      cells. AIM: This study further evaluated the effects of morusinol, a flavonoid
      derived from Morus alba root bark, on platelet aggregation and thromboxane B(2)
      (TXB(2) formation in vitro and thrombus formation in vivo. METHODS: The
      antiplatelet potential of morusinol was measured using in vitro rabbit platelet
      aggregation and TXB(2) formation assays. Arterial thrombus formation was
      investigated using an in vivo ferric chloride (FeCl(3)-induced thrombosis model.
      RESULTS: Morusinol significantly inhibited collagen- and arachidonic acid-induced
      platelet aggregation and TXB(2) formation in cultured platelets in a
      concentration-dependent manner. Thrombus formation was reduced by 32.1, 42.0, and
      99.0% for collagen-induced TXB(2) formation, and 8.0, 24.1, and 29.2% for
      arachadonic acid-induced TXB(2) formation, with 5, 10, and 30 ug/mL morusinol,
      respectively. Moreover, oral morusinol (20 mg/kg) or aspirin (20 mg/kg) for three
      days significantly increased the time to occlusion in vivo by 20.3+/-5.0 or 6.8+/
      2.9 min, respectively, compared with the control (1% CMC, carboxymethyl
      cellulose). CONCLUSION: Taken together, these results indicate that morusinol may
      significantly inhibit arterial thrombosis in vivo due to antiplatelet activity.
      Thus, morusinol may exert beneficial effects on transient ischemic attacks or
      stroke via the modulation of platelet activation.

PMID- 22472212
TI  - Mannose-binding lectin in obesity with different degrees of metabolic syndrome
      abnormalities: association with atherogenic and metabolic traits.
AB  - AIM: In subjects with metabolic syndrome (MetS) endothelial dysfunction is a very
      consistent finding. Processes leading to endothelial dysfunction and
      atherosclerosis involve the altered control of subclinical inflammation by innate
      immune defenses that possibly include mannose-binding lectin (MBL). We
      investigated the associations of MBL with traits of MetS and early
      atherosclerosis in obese subjects before and after marked weight reduction.
      METHODS: In a prospective longitudinal study, MBL concentrations of 96 severely
      obese subjects with and without MetS (O BMI with MetS 41.0+/-7.9 kg/m(2), O BMI
      without MetS 39.4+/-7.7 kg/m(2) were examined in association with markers of
      insulin resistance, dyslipidemia, adipokines, and subclinical atherosclerosis
      before and after marked weight loss (O weight loss 20+/-8 kg after 3 months of
      participation in a standardized weight reduction program), in addition to the
      study of 25 seemingly healthy lean subjects (BMI 20-25 kg/m(2). RESULTS: MBL
      concentrations did not differ between healthy lean and severely obese subjects
      independently of the presence of metabolic abnormalities. In severely obese
      subjects there was no significant difference concerning the cardiovascular risk
      profile, apolipoproteins, inflammatory and metabolic parameters, and markers of
      endothelial dysfunction and atherosclerosis between subjects with functional MBL
      deficienct (MBL<778 ng/mL) and MBL sufficient (MBL>=778 ng/mL) obesity. Marked
      weight loss did not influence MBL levels. CONCLUSIONS: Our findings suggest that
      plasma levels of MBL did not differ between healthy lean and severely obese
      subjects. MBL did not affect cardiovascular risk factors, or markers of
      endothelial dysfunction and early atherosclerosis in severely obese patients
      before and after marked weight loss.

PMID- 22472213
TI  - Effects of PPIs and an H2 blocker on the antiplatelet function of clopidogrel in
      Japanese patients under dual antiplatelet therapy.
AB  - AIM: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is essential
      after percutaneous coronary intervention (PCI). Clopidogrel is a prodrug and
      changed into active metabolite by cytochrome p450 enzymes (CYPs), especially
      CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin
      induced gastrointestinal bleeding. PPIs are also metabolized by CYP2C19, although
      the degree of its contribution is dependent on the kind of PPI. Omeprazole, a
      PPI, has been reported to weaken the antiplatelet effects of clopidogrel.
      Famotidine, a histamine receptor type 2 (H2) blocker, could also be an
      alternative to PPIs. The aim of this study was to evaluate the effects of PPIs
      and an H2 blocker on the antiplatelet function of clopidogrel. METHODS: Patients
      receiving DAPT due to prior PCI, who took either omeprazole or rabeprazole, were
      enrolled (n=25). The initial PPI was changed to the other PPI as a crossover
      study. In another study, patients undergoing DAPT without taking PPIs or H2
      blockers were enrolled (n=30) and famotidine was added. RESULTS: Platelet
      aggregability when taking omeprazole was higher than when taking rabeprazole,
      evaluated by an optical aggregometer using collagen as a stimulus (p=0.0051) and
      by the VerifyNow P2Y12 assay (p=0.0060). Platelet aggregability when taking
      rabeprazole was comparable to that in control patients (n=15). Concomitant use of
      famotidine had no effect. CONCLUSION: Omeprazole significantly reduced the
      antiplatelet effect of clopidogrel and this effect on clopidogrel was stronger
      than that of rabeprazole. Concomitant use of famotidine had no effect on the
      antiplatelet effect of clopidogrel.

PMID- 22472214
TI  - Epicardial fat reflects arterial stiffness: assessment using 256-slice
      multidetector coronary computed tomography and cardio-ankle vascular index.
AB  - AIM: The cardio-ankle vascular index (CAVI) reflects overall arterial stiffness
      from the aorta to the ankle, independent of blood pressure. We aimed to
      investigate the association of fat burden assessed by visceral adipose tissue
      (VAT), subcutaneous adipose tissue (SAT) and epicardial adipose tissue (EAT) with
      CAVI in an asymptomatic population. METHODS: A total of 260 asymptomatic Korean
      individuals who had CAVI, abdominal computed tomography (CT) and coronary CT were
      evaluated retrospectively. The VAT, SAT, EAT and SAT to VAT ratio (SVR) were
      measured and assessed for correlation with CAVI. RESULTS: Different fat
      compartments showed different correlations with arterial stiffness as assessed by
      CAVI. The amount of fat measured by VAT (r= 0.129, p= 0.037), EAT (r=0.193, p=
      0.002) and SVR (r=-0.168, p= 0.007) showed a significant correlation with CAVI,
      whereas the amount of total abdominal fat and SAT did not (p= 0.261 and p= 0.434
      respectively). From step-wise multivariate regression analysis including age,
      pulse pressure, fasting blood sugar level, VAT, SVR and EAT, EAT (p= 0.036) and
      age (p<0.001) showed significant associations with CAVI. When quartiles of CAVI
      were assessed, EAT showed serial increment, whereas SVR showed a stepwise
      decrease from the first quartile to fourth quartile of CAVI (p=0.041).
      CONCLUSION: VAT, EAT and SVR, which reflect metabolic risk, have shown
      significant correlations with arterial stiffness measured by CAVI. EAT showed an
      independent association with arterial stiffness after adjusting for covariables
      by multivariable correlation analysis. Among the different parameters reflecting
      fat burden, EAT showed the strongest correlation with CAVI.

PMID- 22472215
TI  - Coexistence of visceral fat and multiple risk factor accumulations is strongly
      associated with coronary artery disease in Japanese (the VACATION-J study).
AB  - AIM: Multiple risk factor syndrome is a target for the prevention of coronary
      artery disease (CAD). A cluster of multiple risk factors, such as hypertension,
      glucose intolerance, and/or dyslipidemia, is encountered in Japanese without and
      with excess visceral fat. The present study investigated the relationship between
      multiple risk factor accumulation and CAD in Japanese without and with visceral
      fat accumulation. METHODS: The study subjects comprised 257 Japanese with
      suspected CAD (males/females= 153/ 104), who underwent 64-row multislice computed
      tomography (CT) coronary angiography and visceral fat area (VFA) measurement by
      CT. Based on the Japanese criteria for visceral fat accumulation, they were
      divided into those with VFA <100 and >=10 cm(2). RESULTS: In subjects with VFA
      <100 cm(2), the age- and sex-adjusted odds ratios (ORs) for 2 and 3 risk factors
      were 5.33 (95% confidence intervals; 1.04-27.38, p=0.0449) and 4.07 (0.72-23.15,
      p=0.1138), respectively, compared with VFA <100 cm(2) and 0 risk factor set at
      1.0 (p=0.0569 for trend). In contrast, the respective ORs for subjects with VFA
      >=100 cm(2) were much higher [6.46 (1.25-33.44, p=0.0261) and 20.42 (3.60-115.73,
      p=0.0007)] (p<0.0001 for trend). The multivariate adjusted model demonstrated a
      significant relative excess CAD risk of 1.08 (p=0.0484) and 5.01 (p<0.0001) for
      the interactions of 2 risk factors and VFA >=100 cm(2), and 3 risk factors and
      VFA >=100 cm(2), whereas multiple risk factor accumulation was not related with
      the increase of CAD risk in subjects with VFA <100 cm(2). CONCLUSIONS:
      Coexistence of visceral fat and risk factor accumulations is strongly associated
      with CAD in Japanese.

PMID- 22472216
TI  - Hydrogen peroxide-inducible clone 5 (Hic-5) as a potential therapeutic target for
      vascular and other disorders.
AB  - Hydrogen peroxide-inducible clone-5 (Hic-5) is a focal adhesion scaffold protein
      primarily expressed in vascular and visceral smooth muscle cells. We recently
      generated mice lacking Hic-5, which grew with no apparent abnormality (Kim
      Kaneyama J, et al. J Mol Cell Cardiol. 2011;50(1):77-86). However, we discovered
      that recovery of arterial media following vascular injury is delayed
      significantly in Hic-5 knockout mice consequent to enhanced apoptosis of cultured
      vascular smooth muscle cells after mechanical stress; thus, Hic-5 is regarded as
      a novel factor in vascular remodeling. The Hic-5 gene is also induced by
      transforming growth factor-beta, a well-known accelerator in fibrosis. Hic-5
      involvement in various fibrotic disorders, e.g., scar formation, keloid formation
      and glomerulosclerosis, has been proposed. siRNA silencing of Hic-5 in a breast
      cancer cell line reduces its invasiveness; moreover, Hic-5 serves as a steroid
      hormone co-activator and likely participates in endometriosis and prostate
      cancer. Thus, functional characterization of Hic-5 in various pathophysiological
      conditions may afford novel mechanistic insights into a wide variety of diseases.

PMID- 22472219
TI  - Antipsychotic medications: linking receptor antagonism to neuropsychological
      functioning in first episode psychosis.
AB  - Antipsychotic medications can contribute to neurocognitive and motor impairments,
      but specific links to individualized pharmacological treatment regimens are
      unclear. In 68 participants with stabilized first-episode psychosis (FEP), we
      investigated the links between neuropsychological functions and an established
      anticholinergic potency index and a new D(2) antagonist potency index developed
      in our lab. Each participant's psychiatric medication regimen was converted into
      estimated receptor antagonist loads based upon specific medication dosage(s) and
      reported in vitro brain muscarinic cholinergic and D(2) receptor antagonism. In
      addition to the global neuropsychological impairments of FEP participants, the
      findings supported the hypothesized links between receptor antagonist loads and
      specific deficits. Higher anticholinergic load was associated with poorer delayed
      verbal memory but was not related to motor functioning. In contrast, higher D(2)
      load was associated with poorer motor functioning but not verbal memory. These
      selective antagonist load associations explained 19% of the variance in motor
      functioning and 17% of the variance in delayed verbal memory. Evidently, some of
      the neuropsychological impairments found in persons with FEP are selectively
      related to the specific pharmacodynamics and the dosing of their medication
      regimens. Moreover, these effects can be readily estimated from practical and
      inexpensive indices.

PMID- 22472218
TI  - Functional repertoire, molecular pathways and diseases associated with 3D domain
      swapping in the human proteome.
AB  - BACKGROUND: 3D domain swapping is a novel structural phenomenon observed in
      diverse set of protein structures in oligomeric conformations. A distinct
      structural feature, where structural segments in a protein dimer or higher
      oligomer were shared between two or more chains of a protein structure,
      characterizes 3D domain swapping. 3D domain swapping was observed as a key
      mediator of numerous functional mechanisms and play pathogenic role in various
      diseases including conformational diseases like amyloidosis, Alzheimer's disease,
      Parkinson's disease and prion diseases. We report the first study with a focus on
      identifying functional classes, pathways and diseases mediated by 3D domain
      swapping in the human proteome. METHODS: We used a panel of four enrichment tools
      with two different ontologies and two annotations database to derive biological
      and clinical relevant information associated with 3D domain swapping. Protein
      domain enrichment analysis followed by Gene Ontology (GO) term enrichment
      analysis revealed the functional repertoire of proteins involved in swapping.
      Pathway analysis using KEGG annotations revealed diverse pathway associations of
      human proteins involved in 3D domain swapping. Disease Ontology was used to find
      statistically significant associations with proteins in swapped conformation and
      various disease categories (P-value < 0.05). RESULTS: We report meta-analysis
      results of a literature-curated dataset of human gene products involved in 3D
      domain swapping and discuss new insights about the functional repertoire, pathway
      associations and disease implications of proteins involved in 3D domain swapping.
      CONCLUSIONS: Our integrated bioinformatics pipeline comprising of four different
      enrichment tools, two ontologies and two annotations revealed new insights into
      the functional and disease correlations with 3D domain swapping. GO term
      enrichment were used to infer terms associated with three different GO
      categories. Protein domain enrichment was used to identify conserved domains
      enriched in swapped proteins. Pathway enrichment analysis using KEGG annotations
      revealed that proteins with swapped conformations are present in all six classes
      of KEGG BRITE hierarchy and significantly enriched KEGG pathways were observed in
      five classes. Five major classes of disease were found to be associated with 3D
      domain swapping using functional disease ontology based enrichment analysis. Five
      classes of human diseases: cancer, diseases of the respiratory or pulmonary
      system, degenerative diseases of the central nervous system, vascular disease and
      encephalitis were found to be significant. In conclusion, our study shows that
      bioinformatics based analytical approaches using curated data can enhance the
      understanding of functional and disease implications of 3D domain swapping.

PMID- 22472220
TI  - Segregating the comprehension and elaboration processing of verbal jokes: an fMRI
      study.
AB  - The comprehension-elaboration theory of humor claims that the elicitation of
      humor can be segregated into two stages, comprehension and elaboration.
      Comprehension includes detection and resolution of incongruity, and elaboration
      involves inducement of the experience of amusement. Previous imaging research has
      sought to identify the neural substrates of humor processing by comparing funny
      and unfunny conditions. However, such studies have not been able to segregate the
      comprehension and elaboration stages. The present study was designed to
      differentiate the respective brain areas corresponding to comprehension and
      elaboration with an additional condition, garden path sentences. The results
      suggest that the bilateral inferior frontal gyri and left superior frontal gyrus
      may be associated with humor comprehension, whereas the cortical region in left
      ventromedial prefrontal cortex and the subcortical regions in bilateral amygdalae
      and bilateral parahippocampal gyri may be responsible for the feeling of
      amusement during the elaboration process.

PMID- 22472221
TI  - Laryngeal development and anatomy.
AB  - Knowledge of laryngeal and tracheobronchial development and anatomy is essential
      to the pediatric airway endoscopist. Normal and pathologic airway anatomy is
      discussed in this chapter.

PMID- 22472222
TI  - Flexible bronchoscopy.
AB  - Flexible bronchoscopy is an important procedure for evaluating the pediatric
      airway, allowing a dynamic view from the trachea through the lower bronchi. The
      flexible bronchoscope offers greater maneuverability than the rigid bronchoscope
      and may be done in conjunction with other procedures, such as bronchoalveolar
      lavage, transbronchial biopsy, endobronchial ultrasound, electrocautery or laser
      treatments. Common indications for flexible bronchoscopy include recurrent croup
      or pneumonia, aspiration, foreign body and chronic cough. Although bronchospasm,
      transient fever, infection and pneumothorax are rare complications of flexible
      bronchoscopy, these risks are minimized with careful technique and an ongoing
      dialogue with the anesthesiologist. Flexible bronchoscopy is an important tool in
      the diagnosis, monitoring and therapy of certain pulmonary diseases and should be
      considered in the management of carefully selected pediatric patients.

PMID- 22472223
TI  - Direct laryngoscopy and rigid bronchoscopy.
AB  - Laryngoscopy and rigid bronchoscopy represent a necessary tool in the
      otolaryngologist's arsenal. The advancement in designing smaller and more
      versatile laryngeal equipment and fiber-optic telescopes as well as the
      increasingly higher resolution of still and video imagery have allowed
      otolaryngologists to better diagnose and treat many airway lesions. This chapter
      describes the basic equipment necessary as well step-by-step description of the
      technique to perform rigid airway endoscopy.

PMID- 22472224
TI  - Pediatric tracheotomy.
AB  - The procedure of tracheotomy dates back to ancient times. Its use has been
      adapted in the neonatal and pediatric population over the past half-century.
      Despite being a life-saving measure, tracheotomy-related mortality rates range
      from 0.5 to 3.6%, and this procedure is not without significant and sometimes
      frequent complications. Techniques regarding pediatric tracheotomy vary from
      surgeon to surgeon and include orientation of skin incision, removal of
      subcutaneous tissue, orientation of tracheotomy, maturation and stay sutures, as
      well postoperative care and surveillance. In this chapter, the authors detail
      their technique for tracheotomy. Surgical pearls for success are highlighted.

PMID- 22472225
TI  - Laryngotracheal reconstruction.
AB  - Laryngotracheal reconstruction (LTR) along with cricotracheal resection and
      thyrotracheal anastomosis has become the standard of care for symptomatic
      subglottic stenosis in the pediatric age group. Success rates in achieving
      decannulation or avoiding tracheotomy approach 90%. Fearon and Cotton introduced
      pediatric LTR in 1972 using cartilage interposition grafting. The procedure has
      evolved to include a variety of techniques for expanding the laryngotracheal
      complex to obtain a stable airway of sufficient size for respiration. In this
      chapter, the authors will describe their single and double-stage technique for
      LTR highlighting surgical pearls necessary for success.

PMID- 22472226
TI  - Costal cartilage harvest.
AB  - Cartilage interposition grafting for treatment of subglottic stenosis was
      pioneered by Fearon and Cotton in 1972. Costal cartilage is the preferred source
      for graft material in most cases. In this section, the authors highlight the
      surgical technique for cartilage graft harvest with discussion of surgical pearls
      necessary for success.

PMID- 22472227
TI  - Cricotracheal resection and thryotracheal anastomosis.
AB  - Cricotracheal resection and thryotracheal anastomosis along with laryngotracheal
      reconstruction have become the standard of care for symptomatic subglottic
      stenosis in the pediatric age group with decannulation rates approaching 90%. The
      procedure is ideal for children with subglottic stenosis several millimeters
      distal to the true vocal cords and can be extended to include costal
      interposition grafting if necessary. In this chapter, the authors describe the
      surgical techniques necessary for successful resection and reanastomosis.

PMID- 22472228
TI  - Tracheal resection and reanastomosis.
AB  - Isolated short segment tracheal stenosis occurs in a relatively rare
      subpopulation of patients with laryngotracheal stenosis. Etiologies include both
      acquired and congenital, the most common being the acquired type. Management
      options include observation, endoscopic balloon dilation with or without CO(2)
      laser, stent placement and open airway surgery. In this chapter, we will discuss
      tracheal resection and reanastomosis with emphasis on surgical pearls for
      success.

PMID- 22472229
TI  - Slide tracheoplasty.
AB  - Slide tracheoplasty, first described in 1989, has become the procedure of choice
      for long segment tracheal stenosis and complete tracheal rings. Although a
      challenging surgery with higher mortality than other open airway procedures, this
      technique offers a successful alternative for parents who just a couple decades
      ago had no reasonable surgical option. We describe the management of long segment
      tracheal stenosis using the slide tracheoplasty highlighting the surgical pearls
      necessary for success.

PMID- 22472230
TI  - Suprastomal granuloma.
AB  - Suprastomal granuloma is one of the most common sequelae of pediatric
      tracheotomy. Numerous different techniques have been described for their removal
      including endoscopic and open procedures. The following chapter discusses the
      intraoperative techniques for open removal of suprastomal granuloma in infants.

PMID- 22472231
TI  - Thyroglossal duct cyst excision.
AB  - Thyroglossal duct cysts (TGDCs) are the most common congenital anomaly of the
      neck. The most common presentation of TGDCs is a firm, midline mass. The Sistrunk
      procedure is the recommended treatment for TGDCs. Based on anatomic and
      embryologic study, Dr. Sistrunk recommended removal of not only the cyst and
      central portion of the hyoid bone, but also a central core of deep tongue
      musculature. By doing so, the rate of recurrence is decreased from approximately
      50 to 3-5%. In this chapter, the authors will describe the Sistrunk procedure
      step by step including surgical pearls for success.

PMID- 22472232
TI  - Bilateral submandibular gland excision and parotid duct ligation.
AB  - Sialorrhea affects a significant number of children with cerebral palsy and other
      neuromuscular disorders. It can lead not only to social embarrassment but also to
      severe medical issues including chronic aspiration. There are numerous medical
      and surgical options, which include oral medications and transdermal patches,
      botulinum injection, and various forms of surgical ligation or excision of the
      major salivary glands. In this chapter, the authors describe the surgical
      management of sialorrhea, highlighting surgical pearls necessary for success.

PMID- 22472233
TI  - Tracheocutaneous fistula closure.
AB  - Tracheocutaneous fistula (TCF) is one of the recognized sequelae of tracheotomy
      in the pediatric age group. Persistent TCF can cause considerable morbidity due
      to recurrent aspiration, and subsequent respiratory infection, difficulty in
      phonation, ineffective cough, skin irritation, cosmesis, social acceptance, and
      intolerance to submersion. Methods of TCF closure remain controversial and vary
      based on the otolaryngologist's preference. The authors' choice is fistulectomy
      with primary closure in layers as this definitively removes the fistula and
      provides the patient with a good cosmetic result without the need for any
      significant postoperative wound care. The following chapter describes our
      techniques as well as surgical pearls for success.

PMID- 22472235
TI  - Pediatric laryngeal electromyography.
AB  - Vocal fold immobility (VFI) is a challenging management issue in pediatric
      otolaryngology. VFI is most commonly distinguished between unilateral (UVFI) and
      bilateral (BVFI) dysfunction. UVFI and BVFI are different pathophysiologic and
      clinical entities with distinct symptoms and etiologies. It has been generally
      accepted in the adult literature to wait at least 1 year prior to carrying out
      more permanent type procedures for VFI. This period has been extended out even
      further in children as the literature has suggested that vocal fold function may
      return many years later. Unfortunately, there is no simple test or procedure to
      help predict return of vocal fold function. In adult patients LEMG has been used
      to help guide management decisions, but it has not been widely investigated in
      children. In this chapter the authors describe a LEMG technique that has been a
      useful adjunct in managing children with VFI.

PMID- 22472234
TI  - Pediatric ansa cervicalis to recurrent laryngeal nerve anastomosis.
AB  - This chapter reviews laryngeal reinnervation with ansa cervicalis for treatment
      of unilateral vocal fold paralysis and glottal incompetence in children. The
      relevant anatomy is discussed; the indications and contraindications are
      detailed. This is followed by a stepwise description of the surgical details of
      this operation.

PMID- 22472236
TI  - Vocal fold injection medialization laryngoplasty.
AB  - Unilateral vocal fold paralysis (UVFP) can cause glottic insufficiency that can
      result in hoarseness, chronic cough, dysphagia, and/or aspiration. In rare
      circumstances, UVFP can cause airway obstruction necessitating a tracheostomy.
      The treatment options for UVFP include observation, speech therapy, vocal fold
      injection medialization laryngoplasty, thyroplasty, and laryngeal reinnervation.
      In this chapter, the author will discuss the technique of vocal fold injection
      for medialization of a UVFP.

PMID- 22472237
TI  - Laryngeal cleft.
AB  - Laryngeal cleft, first described by Richter in 1792, is a rarecongenital
      malformation. Diagnosis can be challenging and is contingent upon a high index of
      suspicion based on clinical presentation, interpretation of preoperative studies
      and a thorough endoscopic evaluation under general anesthesia whereby the
      posterior glottis is carefully palpated for any evidence of a cleft. Management
      involves feeding and medical therapy. When this fails, endoscopic repair is
      possible in type 1, 2 and selective type 3 laryngeal clefts. We describe the
      diagnosis and endoscopic management of type 1 laryngeal clefts, highlighting
      surgical pearls necessary for success.

PMID- 22472238
TI  - Pediatric supraglottoplasty.
AB  - Laryngomalacia is the most common congenital laryngeal abnormality, as well as
      the most common cause of stridor in infants. Laryngomalacia presents as a wide
      spectrum of disease from mild noisy breathing with feeding to life-threatening
      airway obstruction and failure to thrive. The stridor associated with
      laryngomalacia is generally inspiratory in nature from supraglottic airway
      collapse. Supraglottoplasty refers to a group of procedures used for the surgical
      management of laryngomalacia. In this chapter, the authors review laryngomalacia
      and describe the surgical techniques of supraglottoplasty.

PMID- 22472239
TI  - Juvenile-onset recurrent respiratory papillomatosis.
AB  - Juvenile-onset recurrent respiratory papillomatosis, caused by the human
      papilloma virus, is the most common benign neoplasm of the larynx in children.
      Recurrent respiratory papillomatosis is relatively rare, but it can have a
      significant impact on afflicted children and their family's quality of life as
      dysphonia and multiple surgical procedures are hallmarks of this disease. The
      current standard of care is surgical therapy with a goal of complete papilloma
      removal and preservation of normal structures. The technique in this atlas
      combines both the microdebrider and the pulse KTP laser. The microdebrider allows
      for rapid removal of bulky lesions without the risk of thermal injury, yet it
      cannot provide precise removal in areas such as the anterior commissure and
      ventricle. The pulse KTP laser allows for removal of sessile lesions and in
      sensitive areas such as the vocal folds. The authors describe this technique as
      well as discuss adjuvant therapies and pearls for success.

PMID- 22472240
TI  - Pediatric lingual tonsillectomy.
AB  - Tonsillectomy and adenoidectomy are an effective surgical treatment of pediatric
      obstructive sleep apnea; however, up to 20% of these patients can have persistent
      disease. In this select patient population, the lingual tonsil may be an occult
      source of obstruction. Lingual tonsillectomy can be a challenging procedure due
      to poor access and visualization, airway edema, postoperative pain and hemostasis
      during tissue removal. In this chapter, we describe our preferred technique for
      lingual tonsillectomy including surgical pearls for success.

PMID- 22472241
TI  - Pediatric airway balloon dilation.
AB  - Over the past decade, there has also been renewed interest in serial dilatation
      for the management of subglottic and tracheal stenosis with the advent of new
      technologies such as airway balloons designed for the pediatric airway. In this
      chapter, the authors describe the technique of application of airway balloons as
      a useful adjunct for management of airway lesions.

PMID- 22472242
TI  - Endoscopic posterior cricoid split with rib grafting.
AB  - Bilateral vocal fold immobility (BVFI) can be divided into bilateral vocal fold
      paralysis and cricoarytenoid joint fixation, which can be accompanied with
      laryngeal stenosis. In children with BVFI, requiring a tracheostomy, the authors
      preference, to achieve decannulation, is to perform an endoscopic posterior
      cricoid split with rib grafting after the age of 1.

PMID- 22472243
TI  - Vocal cordotomy.
AB  - Congenital bilateral vocal fold paralysis (BVFP) is the second most common cause
      of stridor in neonates. Etiologies of BVFP include neurologic, cardiopulmonary
      malformations, iatrogenic, traumatic, and idiopathic. One half of children with
      BVFP will require a tracheostomy for upper airway obstruction. Because more than
      50% of BVFP will resolve spontaneously, many advocate surgical intervention to
      achieve decannulation after the age of one. The goal of surgery is to provide an
      adequate airway to allow decannulation with minimal impact on speech and
      swallowing. There is no one procedure accepted as the gold standard or first-line
      treatment to achieve decannulation in children with BVFP. The author's preference
      is to perform a vocal cordotomy as a first line for an endoscopic approach.

PMID- 22472244
TI  - Endoscopic choanal atresia repair.
AB  - Congenital choanal atresia (CA) is relatively rare, with an incidence of 1 in
      7,000 births with a majority being the mixed bony-membranous type. There are 5
      described methods of CA repair: transpalatal, transnasal, sublabialtransnasal,
      transantral, and transseptal approaches. Transpalatal and transnasal have been
      the most popular in the last several decades with transnasal becoming the
      preferred technique with the advent of endoscopic instruments and techniques. In
      this chapter, the authors seek to describe their techniques for endoscopic
      transnasal repair of CA including surgical pearls for success.

PMID- 22472245
TI  - Endoscopic resection of juvenile nasopharyngeal angiofibroma.
AB  - Juvenile nasopharyngeal angiofibromas remain rare tumors representing
      approximately 0.05% of head and neck tumors. The typical presentation is a male
      teenager with recurrent epistaxis and nasal obstruction. These tumors were
      traditionally approached via external and/or intraoral incisions, but many are
      amenable to endoscopic removal. Preoperative embolization of major feeding
      vessels to these tumors by interventional radiology has resulted in significantly
      less blood loss and facilitated endoscopic resection. The following chapter
      discusses endoscopic resection of juvenile nasopharyngeal angiofibromas and
      outlines pertinent anatomy while covering important surgical techniques.
      Appropriate patient selection, anesthesia considerations, surgical preparation
      and techniques, and postoperative care are discussed. A case presentation is
      included with preoperative imaging and an accompanying video to demonstrate these
      surgical techniques.

PMID- 22472247
TI  - Double-reversing z-plasty (Furlow palatoplasty).
AB  - Dr. Leonard Furlow first described the double-reversing z-plasty technique for
      cleft soft palate repair in 1978. This approach allows for repair of an overt or
      submucous cleft palate, but just as an importantly, provides additional length to
      the palate and also realigns the palatal musculature. The Furlow palatoplasty
      (the name by which the procedure is commonly referred) has therefore been
      instrumental in the treatment of velopharyngeal insufficiency. The primary aims
      of this chapter are to provide the clinician with the indications for when to
      consider utilizing the Furlow palatoplasty and to give a stepwise description of
      how to perform the procedure.

PMID- 22472246
TI  - Surgery for velopharyngeal insufficiency.
AB  - Velopharyngeal inadequacy may be learned, neurologic, or anatomic in origin.
      Velopharyngeal insufficiency specifically refers to an anatomic deficiency, which
      subsequently impairs resonant control of speech and intraoral pressure for orally
      directed speech sounds. Preoperative speech therapy is useful, and in some
      children may provide definitive treatment. However, surgery is the foundation of
      effective treatment in most patients with anatomic defects and, when used
      appropriately, has been shown to result in resolution of velopharyngeal
      insufficiency in 62-98% of cases. In this chapter, the authors review
      velopharyngeal inadequacy and discuss the techniques necessary for successful
      surgical treatment.

PMID- 22472248
TI  - Pediatric sialendoscopy.
AB  - Sialendoscopy was introduced in the early 1990s as a minimally invasive
      alternative to standard methods for diagnosis and treatment of inflammatory and
      obstructive salivary gland disease. The technique was pioneered in adults;
      however, advances in instrumentation have allowed this to be adapted to the
      smaller salivary ductal anatomy found in the pediatric population. In this
      chapter, the technique of sialendoscopy for parotid and submandibular glands is
      described.

PMID- 22472249
TI  - Lessons from the amblyopia treatment studies.

PMID- 22472250
TI  - Crosslinking for recurrent keratoconus.

PMID- 22472251
TI  - Intravitreal methotrexate in uveitis.

PMID- 22472252
TI  - Anterior ischemic optic neuropathy.

PMID- 22472253
TI  - ORBIS telemedicine users.

PMID- 22472254
TI  - Collaboration in Chinese ophthalmology.

PMID- 22472256
TI  - Pupil size and LASIK.

PMID- 22472257
TI  - Repeat penetrating keratoplasty.

PMID- 22472258
TI  - Pupil size and LASIK.

PMID- 22472260
TI  - Myopic optic disc changes in adolescents.

PMID- 22472261
TI  - Geographic atrophy and visual function.

PMID- 22472263
TI  - Acupuncture therapy for amblyopia.

PMID- 22472265
TI  - Uveitis is a subspeciality.

PMID- 22472267
TI  - Acute effects of aerobic exercise on mood and hunger feelings in male obese
      adolescents: a crossover study.
AB  - BACKGROUND: The aim of this study was to determine the acute effects of exercise
      intensity on anxiety, mood states and hunger in obese adolescents. METHODS:
      Subjects were eight male obese adolescents (age 15.44 +/- 2.06 y; BMI 33.06 +/-
      4.78 kg/m2). Each subject underwent three experimental trials: (1) Control,
      seated for 30 min; (2) Low intensity exercise (LIE)--exercise at 10% below
      ventilatory threshold (VT); (3) High intensity exercise (HIE)--exercise at 10%
      above VT. Anxiety (STAI Trait/State), mood (POMS) and hunger (VAS) were assessed
      before and immediately after the experimental sessions. Comparisons between
      trials and times were assessed using Kruskal-Wallis and Wilcoxon tests,
      respectively. Associations between variables were described using a Spearman
      test. RESULTS: The largest increase in hunger was observed after LEI (914.22%).
      Both exercise sessions increased anxiety, fatigue and decreased vigor (p < 0.05).
      CONCLUSIONS: Acute exercise bouts are associated with negative changes in anxiety
      and mood, and with increases in hunger in obese adolescents.

PMID- 22472268
TI  - Evaluation of clinical aspects and quality of life as risk factors for depression
      in patients with epilepsy.
AB  - The purpose of this study was to investigate clinical aspects and quality of life
      (QOL) as risk factors for depression in patients with epilepsy. One hundred and
      forty outpatients with a diagnosis of epilepsy who were attending our epilepsy
      center participated. Patients anonymously filled out a questionnaire with
      clinical data related to epilepsy. Depression level was evaluated by the Hamilton
      Depression Rating Scale-17 (HAMD-17), and quality of life was evaluated by the
      Quality of Life in Epilepsy-31 (QOLIE-31). Thirty-six patients with epilepsy
      suffered from depression (25.7%). Complex partial seizures (OR=0.112) and number
      of seizure types (OR=3.773) were found to be clinical risk factors for
      depression. Low scores for seizure worry (OR=0.947) and social function
      (OR=0.947) on the QOLIE-31 increased the probability of depression in patients
      with epilepsy.

PMID- 22472269
TI  - Sequential occurrence of thrombotic thrombocytopenic purpura, essential
      thrombocythemia, and idiopathic thrombocytopenic purpura in a 42-year-old African
      American woman: a case report and review of the literature.
AB  - INTRODUCTION: Thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic
      purpura are two well recognized syndromes that are characterized by low platelet
      counts. In contrast, essential thrombocythemia is a myeloproliferative disease
      characterized by abnormally high platelet numbers.The coexistence of thrombotic
      thrombocytopenic purpura and idiopathic thrombocytopenic purpura in a single
      patient has been reported in the literature on a few occasions. However, having
      essential thrombocythemia complicating the picture has never been reported
      before. CASE PRESENTATION: We present a case where thrombotic thrombocytopenic
      purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura were
      diagnosed in a 42-year-old African-American woman in the space of a few years; we
      are reporting this case with the aim of drawing attention to this undocumented
      occurrence, which remains under investigation. CONCLUSIONS: As the three
      conditions have different natural histories and require different treatment
      modalities, it is important to recognize that these diseases may be seen
      sequentially. This case emphasizes the importance of reviewing peripheral blood
      smears for evaluation of thrombocytopenia and bone marrow aspirations for
      diagnosis of thrombocythemia in order to reach an accurate diagnosis and tailor
      therapy accordingly. Moreover, this case demonstrates the variability and
      complexity of platelet disorders. This occurrence of three different types of
      platelet disorders in one patient remains a pure observation on our part;
      regardless, this does raise the possibility of a common underlying, as yet
      undiscovered, pathophysiology that could explain the phenomenon.

PMID- 22472270
TI  - Double-bundle anterior cruciate ligament reconstruction using bone-patellar
      tendon-bone allograft: technique and 2- to 5-year follow-up.
AB  - BACKGROUND: Nonanatomic transtibial single-bundle anterior cruciate ligament
      reconstruction (SB-ACLR) with a bone-patellar tendon-bone (BPTB) allograft has
      been used for a long time and has shown the same satisfactory clinical results as
      an autograft; however, it has not been reported if a double-bundle ACLR (DB-ACLR)
      could be performed with a BPTB allograft and achieve even better results.
      HYPOTHESIS: The DB-ACLR with a BPTB allograft is technically feasible and will be
      superior to the SB technique in restoring better anterior and rotating stability.
      STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The study was
      performed with 56 patients, and 52 (25 in the DB group and 27 in the SB group) of
      them were followed up at 2 to 5 years. With an irradiated deep-frozen BPTB
      allograft, a standard single-incision arthroscopic technique was used, and the
      graft was fixed with bioabsorbable interference screws on both the femoral and
      tibial sides. Outcome assessment at final follow-up included International Knee
      Documentation Committee (IKDC), Tegner, and Lysholm scores; side-to-side
      difference by conventional KT-2000 arthrometer; total anteroposterior (AP) laxity
      by the back-pushing KT-2000 arthrometer; pivot shift (0, +, ++); range of motion
      (ROM); and isokinetic muscle strength evaluation. RESULTS: Mean follow-up was
      47.3 +/- 11.5 and 58.2 +/- 6.6 months for the DB group and SB group,
      respectively. A statistically significant difference in favor of the DB group was
      found with the total AP laxity at 30 degrees  (P < .05). The overall incidence of
      pivot shift in the DB group (4% ++) was significantly lower than that in the SB
      group (26%: 19% + and 7% ++; P = .029). No significant differences were found
      between the 2 groups in terms of IKDC score, Lysholm score, Tegner score,
      conventional KT-2000 arthrometer anterior laxity, ROM, and muscle strength.
      CONCLUSION: A DB-ACLR with a BPTB allograft is feasible and achieved more
      satisfactory results than the transtibial SB technique in terms of total AP
      stability and rotational stability in spite of no significant differences among
      other clinical parameters.

PMID- 22472271
TI  - Hip morphological characteristics and range of internal rotation in
      femoroacetabular impingement.
AB  - BACKGROUND: Radiographic features specifically related to the occurrence of
      femoroacetabular impingement (FAI) appear to be highly prevalent in the
      asymptomatic population. It remains unclear, however, how these incidental
      findings should be interpreted clinically and which other variables might
      differentiate between true incidental findings and preclinical patients. PURPOSE:
      To study the association between cam and overall hip morphological
      characteristics and range of motion in impingement patients, asymptomatic
      patients (healthy patients with radiographic features specific to FAI), and
      healthy controls. STUDY DESIGN: Cross-sectional study; Level of evidence, 3.
      METHODS: Morphological parameters describing cam and overall hip anatomy were
      obtained from 30 patients (10 per subgroup) with use of 3-dimensional
      computational methods. In addition, the range of internal rotation in high
      flexion activities was evaluated, and its relation to hip morphological variables
      was analyzed in a multivariate regression model. RESULTS: Size of the cam lesion
      and range of motion significantly differed between groups (P < .05). The range of
      internal rotation on impingement testing was found to average 27.9 degrees  in
      the healthy control group compared with 21.1 degrees  in the asymptomatic control
      group with radiographic features specific to FAI (P < .001) and 12.3 degrees  in
      the patient group (P < .001). Cam size, acetabular coverage, and femoral version
      appeared to be predictive variables for the range of internal rotation. Seventy
      five percent of variance between patients could be attributed to the combined
      effect of these 3 variables (R = .86). The range of motion was decreased in cam
      patients and asymptomatic patients, and early femoroacetabular conflict was not
      restricted to the area of the cam lesion but involved the entire anterior femoral
      head-neck junction. CONCLUSION: Decreased range of motion, as found in FAI, is
      not solely dependent on the size or even the occurrence of a cam lesion but
      should be interpreted by taking into account the overall hip anatomy,
      specifically femoral version and acetabular coverage. Decreased femoral
      anteversion and increased acetabular coverage add to the risk of early
      femoroacetabular collision during sports and activities of daily living and
      therefore appear to be additional predictive variables, besides the finding of a
      cam lesion, for the risk of clinical hip impingement development. In addition,
      the findings suggest that surgical osteochondroplasty to restore a normal range
      of motion may necessitate more excessive bone resection than what simply appears
      to be a bump on imaging.

PMID- 22472272
TI  - Patellar tendon healing with platelet-rich plasma: a prospective randomized
      controlled trial.
AB  - BACKGROUND: The patellar tendon has limited ability to heal after harvesting its
      central third. Platelet-rich plasma (PRP) could improve patellar tendon healing.
      HYPOTHESIS: Adding PRP to the patellar tendon harvest site would improve donor
      site healing and improve clinical outcome at 6 months after anterior cruciate
      ligament (ACL) reconstruction with a patellar tendon graft. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: Twenty-seven patients
      were randomly divided to receive (n = 12) or not receive (n = 15) PRP in the
      patellar tendon harvest site during ACL reconstruction. The primary outcome was
      magnetic resonance imaging (MRI) assessment of patellar tendon healing (gap area)
      after 6 months. Secondary outcomes were questionnaires and isokinetic testing of
      ACL reconstruction with a patellar tendon graft comparing both groups. RESULTS:
      Patellar tendon gap area was significantly smaller in the PRP group (4.9 +/- 5.3
      mm(2); 95% confidence interval [CI], 1.1-8.8) than in the control group (9.4 +/-
      4.4 mm(2); 95% CI, 6.6-12.2; P = .046). Visual analog scale score for pain was
      lower in the PRP group immediately postoperatively (3.8 +/- 1.0; 95% CI, 3.18
      4.49) than in the control group (5.1 +/- 1.4; 95% CI, 4.24-5.90; P = .02). There
      were no differences after 6 months in questionnaire and isokinetic testing
      results comparing both groups. CONCLUSION: We showed that PRP had a positive
      effect on patellar tendon harvest site healing on MRI after 6 months and also
      reduced pain in the immediate postoperative period. Questionnaire and isokinetic
      testing results were not different between the groups at 6 months.

PMID- 22472273
TI  - Alzheimer's disease 2012: the great amyloid gamble.
AB  - Alzheimer's disease threatens to become the scourge of the 21st century. Hundreds
      of millions of aging people throughout the world are at risk, but it is clear
      that the disease encompasses more than just the natural aging process. Deposits
      of amyloid beta peptides in the brains of demented individuals are a defining
      feature of the disease, yet two decades of intensive investigation, focusing on
      reducing or removing amyloid deposits, have failed to produce any meaningful
      therapeutic interventions. Some researchers question whether amyloid is the
      appropriate target. Others maintain that early, presymptomatic intervention would
      be a more informative test, and propose large-scale clinical trials in patients
      who are believed to be in the earliest, and potentially reversible, stages of the
      disease. This review explores the wisdom of that approach.

PMID- 22472274
TI  - Beyond normality in the study of bereavement: heterogeneity in depression
      outcomes following loss in older adults.
AB  - Studies of individual differences in bereavement have revealed prototypical
      patterns of outcome. However, many of these studies were conducted prior to the
      advent of sophisticated contemporary data analytic techniques. For example,
      Bonanno et al. (2002) used rudimentary categorization procedures to identify
      unique trajectories of depression symptomatology from approximately 3 years prior
      to 4 years following conjugal loss in a representative sample of older American
      adults. In the current study, we revisited these same data using Latent Class
      Growth Analysis (LCGA) to derive trajectories and test predictors. LCGA is a
      technique well-suited for modeling empirically- and conceptually-derived
      heterogeneous longitudinal patterns while simultaneously modeling predictors of
      those longitudinal patterns. We uncovered four discrete trajectories similar in
      shape and proportion to the previous analyses: Resilience (characterized by
      little or no depression; 66.3%), Chronic Grief (characterized by depression
      following loss, alleviated by 4 years post-loss; 9.1%), _Pre-existing Chronic
      Depression (ongoing high pre- through post-loss depression; 14.5%), and Depressed
      Improved (characterized by high pre-loss depression that decreases following
      loss; 10.1%). Using this analytic strategy, we were able to examine multiple
      hypotheses about bereavement simultaneously. Health, financial stress, and
      emotional stability emerged as strong predictors of variability in depression
      only for some trajectories, indicating that depression levels do not have a
      common etiology across all the bereaved. As such, we find that identifying
      distinct patterns informs both the course and etiology of depression in response
      to bereavement.

PMID- 22472275
TI  - Pathways to care: narratives of American Indian adolescents entering substance
      abuse treatment.
AB  - Using data from 89 American Indian adolescents and guided by the Network Episode
      Model, this paper analyses pathways to residential substance abuse treatment and
      their correlates. These adolescents were recruited at admission to a tribally
      operated substance abuse treatment program in the southern United States from
      October 1998 to May 2001. Results from the qualitative analyses of these
      adolescent's pathways to care narratives indicated that 35% ultimately agreed
      with the decision for their entry into treatment; 41% were Compelled to enter
      treatment by others, usually by their parents, parole officers, and judges; and
      24% did not describe a clear pathway to care. In the multinomial logistic
      regression model examining correlates of these pathways to care classifications,
      adolescents who described pathways indicative of agreement also reported greater
      readiness for treatment than the adolescents who described compelled or no clear
      pathways to care. Adolescents who described a Compelled pathway were less likely
      to meet diagnostic criteria for Conduct Disorder and described fewer social
      network ties. We were unable to find a relationship between pathways
      classifications and referral source, suggesting these narratives were subjective
      constructions of pathways to care rather than a factual representation of this
      process. In the final logistic regression model examining correlates of treatment
      completion, articulating a pathway to care, whether it was one of agreement or of
      being compelled into treatment, predicted a greater likelihood of completing
      treatment. Overall, these narratives and their correlates are highly consistent
      with the Network-Episode Model's emphasis on the interaction of self, situation,
      and social network in shaping the treatment seeking process, demonstrating the
      applicability of this model to understanding the treatment seeking process in
      this special population and suggests important considerations for understanding
      the dynamics of service utilization across diverse communities.

PMID- 22472276
TI  - Maternal religious attendance and low birth weight.
AB  - We use data from the U.S. Fragile Families and Child Wellbeing study to test
      whether maternal religious attendance is protective against low birth weight.
      Building on previous research, we also consider the mediating influence of mental
      health, cigarette use, alcohol use, illicit drug use, poor nutrition, and
      prenatal care. Our results indicate that maternal religious attendance is
      protective against low birth weight. In fact, each unit increase in the frequency
      of religious attendance reduces the odds of low birth weight by 15%. Religious
      attendance is also associated with lower odds of cigarette use and poor
      nutrition, but is unrelated to mental health, alcohol use, illicit drug use, and
      prenatal care. Although lower rates of cigarette use help to mediate or explain
      11% of the association between maternal religious attendance and low birth
      weight, we find no evidence to substantiate the mediating influence of mental
      health, alcohol use, illicit drug use, poor nutrition, or prenatal care. Our
      results suggest that the health benefits of religious involvement may extend
      across generations (from mother to child); however, additional research is needed
      to fully explain the association between maternal religious attendance and low
      birth weight. It is also important for future research to consider the extent to
      which the apparent health advantages of religious adults might be attributed to
      health advantages in early life, especially those related to healthy birth
      weight.

PMID- 22472277
TI  - Socioeconomic status and cell aging in children.
AB  - Theory suggests that chronic stress associated with disadvantaged social status
      may lead to acceleration in the rate of decline in physiological functioning. The
      purpose of this study is to examine the association between parental
      socioeconomic status (SES) and leukocyte telomere length (LTL), a marker of cell
      aging, in children. We examined SES and LTL in 70 white and black US children
      aged 7-13 who participated in the community-based AMERICO (Admixture Mapping for
      Ethnic and Racial Insulin Complex Outcomes) study. LTL was assessed using the
      polymerase chain reaction (PCR) method. Parental education was positively
      associated with child LTL, net of controls for sex, age, race/ethnicity, and
      family income. Compared to children with at least one college-educated parent,
      children whose parents never attended college had telomeres shorter by 1,178 base
      pairs, which is roughly equivalent to 6 years of additional aging. Socioeconomic
      disparities in cell aging are evident in early life, long before the onset of age
      related diseases.

PMID- 22472278
TI  - Cell type-associated differences in migration, survival, and immunogenicity
      following grafting in CNS tissue.
AB  - Cell transplantation has been suggested to display several neuroprotective and/or
      neuroregenerative effects in animal models of central nervous system (CNS)
      trauma. However, while most studies report on clinical observations, currently
      little is known regarding the actual fate of the  cell populations grafted and
      whether or how the brain's innate immune system, mainly directed by activated
      microglia and astrocytes, interacts with autologous cellular implants. In this
      study, we grafted well-characterized neural stem cell, mouse embryonic
      fibroblast, dendritic cell, bone  marrow mononuclear cell, and splenocyte
      populations, all isolated or cultured from C57BL/6-eGFP transgenic mice, below
      the capsula externa (CE) of healthy C57BL/6 mice and below the
      inflamed/demyelinated CE of cuprizone-treated C57BL/6 mice. Two weeks
      postgrafting, an extensive quantitative  multicolor histological analysis was
      performed in order (i) to quantify cell graft localization, migration, survival,
      and toxicity and (ii) to characterize endogenous CNS immune responses against the
      different cell grafts. Obtained results indicate dependence on the cell type
      grafted: (i)  a different degree of cell graft migration, survival, and toxicity
      and (ii) a different organization of the endogenous immune response. Based on
      these observations, we warrant that further research should be undertaken to
      understand-and eventually control-cell graft-induced tissue  damage and
      activation of the brain's innate immune system. The latter will be inevitable
      before cell grafting in the CNS can be performed safely and successfully in
      clinical settings.

PMID- 22472279
TI  - Onwards and upwards: European Journal of Medical Research continues as an open
      access publication.
AB  - The well-established European Journal of Medical Research has joined BioMed
      Central's portfolio of journals in January 2012, converting to the open access
      publishing model. Since its launch in 1995 the journal has been a print-only
      publication; from now on, it continues as an open access, online-only journal.
      The conversion to open access opens up the potential for the journal to become a
      leading, globally visible title in the field of general medicine over the coming
      years.

PMID- 22472280
TI  - The optimal dietary fat to carbohydrate ratio to prevent obesity in the Japanese
      population: a review of the epidemiological, physiological and molecular
      evidence.
AB  - The prevention of obesity, which leads to diabetes and other diseases, is a major
      concern for public health. There might be an optimal dietary fat to carbohydrate
      ratio for prevention and treatment of obesity. According to the Japanese Dietary
      Reference Intakes (RDA) for 2010, the optimal fat intake is 20-30% of energy for
      ages 1-29 y and 20-25% for ages 30 y and over. Upper boundary values of this
      recommendation were the median of the percentage of energy from dietary fat in
      Japanese. In a systematic review to estimate the optimal dietary fat to
      carbohydrate ratio, it was found that obese subjects with hyperinsulinemia (or
      insulin resistance) lost more weight on a mild low-carbohydrate (LC) (or low
      glycemic load diet; 40% carbohydrate, 30-35% fat) than on a low-fat (LF) diet (55
      60% carbohydrate, 20% fat), whereas those without hyperinsulinemia showed the
      opposite. In non-obese primarily insulin-sensitive subjects, decreasing fat
      rather than carbohydrate intake is generally more effective to prevent obesity.
      Physiological and molecular evidence supports this conclusion. Increased
      carbohydrate intake, especially in high-glycemic food, leads to postprandial
      hyperglycemia and hyperinsulinemia, which are exaggerated in obese insulin
      resistant subjects. Even in an insulin-resistant state, insulin is able to
      stimulate fatty acid synthesis in liver, activate lipoprotein lipase, and prevent
      lipolysis in adipose tissues, which all facilitate adipose tissue enlargement.
      Optimal dietary fat to carbohydrate ratio may differ in populations depending on
      their prevalence for obesity. Because the prevalence of overweight/obesity in
      Japanese is low, a LF diet is recommended in the general population.

PMID- 22472281
TI  - Fat-free mass can be utilized to assess resting energy expenditure for male
      athletes of different body size.
AB  - The fat-free mass (FFM) of athletes is typically large, and thus the FFM is often
      utilized to estimate their resting energy expenditure (REE). While the
      proportional contribution of organ-tissues to the total influence of FFM on REE
      is known for untrained individuals and female athletes, the extent to which this
      is valid for male athletes is unclear. The purpose of this study was to clarify
      the contribution of the components of FFM to REE in male athletes. Fifty-seven
      male athletes participated in this study. REE was assessed by indirect
      calorimetry and body composition by dual X-ray absorptiometry. The athletes were
      equally divided into three groups based on FFM: Small (S), Medium (M), and Large
      (L). When measured REE (REEm) was compared with REE estimated (REEe) based on the
      four organ-tissue compartments with set metabolic rates, REEm and REEe had a
      strong association (r=0.76, p<0.001). In addition, the absolute value of total
      REE became larger in accordance with body size (S: 1,643+/-144, M: 1,865+/-140,
      and L: 2,060+/-156 kcal/d) accompanied by increases in mass of all four organ
      tissue compartments as body size increased. The consistency of REE/FFM in male
      athletes in spite of the difference in body size can be explained by the
      steadiness among the three groups of the relative contribution of each organ
      tissue compartment to the FFM. Based on these results, the FFM is the major
      determinant of REE regardless of body size in male athletes.

PMID- 22472282
TI  - Muscle protein metabolism during compensatory growth with changing dietary lysine
      levels from deficient to sufficient in growing rats.
AB  - Livestock and laboratory animals show compensatory growth when they are fed ad
      libitum following a period of restriction feeding. Lysine is a major limiting
      essential amino acid in the diets both for humans and animals. We hypothesized
      that changing dietary lysine levels from deficient to sufficient induced
      compensatory growth in young rats. We elucidated the effect of lysine sufficiency
      on the dynamics of hormones, relevant to muscle protein synthesis and
      degradation, insulin-like growth factor-I (IGF-I) and corticosterone, and on the
      expression of proteolytic-related genes in skeletal muscle during compensatory
      growth. Lysine sufficiency where the dietary lysine level was increased from
      0.46% to 1.30% after 2 wk of subjecting the rats to the lower lysine level
      induced 80% enhancement of growth rate of rats. During compensatory growth with
      the lysine sufficiency, fractional muscle protein synthesis rates were higher
      whereas fractional muscle protein degradation rates were lower than those of the
      control group (p<0.05). After lysine sufficiency, the expression of atrogin
      1/MAFbx mRNA was decreased in gastrocnemius muscle (p<0.05). With the lysine
      sufficiency, serum IGF-I concentration increased (p<0.05) whereas serum
      corticosterone decreased (p<0.05). These findings suggest that compensatory
      growth with lysine sufficiency is due to a change of hormone levels before and
      after changing diets, resulting in incrementation of protein synthesis and
      suppression of protein degradation of skeletal muscle.

PMID- 22472283
TI  - Associations between markers of liver injury and cytokine markers for insulin
      sensitivity and inflammation in middle-aged Japanese men not being treated for
      metabolic diseases.
AB  - Elevated circulating alanine aminotransferase (ALT) and gamma
      glutamyltranspeptidase (gamma-GTP) activities in healthy and preclinical subjects
      are associated with increased risk for obesity, diabetes and related
      complications. In the present study, we examined the associations between these
      hepatic enzymes and circulating cytokines as markers for insulin sensitivity
      (adiponectin) and inflammation [interleukin-6 (IL-6)] in middle-aged Japanese men
      not being treated for metabolic diseases. We conducted a cross-sectional study of
      310 Japanese men aged 40-69 y (mean +/- SD, 58.8 +/- 7.6 y) who were not being
      treated for metabolic diseases and who participated in health checkups in Japan.
      We analyzed their lifestyle factors, clinical factors, and plasma adiponectin and
      IL-6 concentrations. We determined associations between the concentrations of
      these cytokines and the clinical and lifestyle factors using Spearman's
      correlation analysis, Jonckheere-Terpstra's test and multiple linear regression.
      ALT activity was negatively associated with adiponectin (r=-0.302, p<0.001) but
      not with IL-6. gamma-GTP activity was positively associated with IL-6 (r=0.335,
      p<0.001) and negatively associated with adiponectin (r=-0.129, p<0.05). Aspartate
      aminotransferase (AST) activity was positively associated with IL-6 (r=0.131,
      p<0.05) and negatively associated with adiponectin (r=-0.125, p<0.05). Multiple
      linear regression analyses showed that adiponectin was independently and
      negatively associated with ALT activity, while IL-6 was independently and
      positively associated with gamma-GTP activity. Adiponectin and IL-6 were not
      independently associated with AST activity. The results of this study indicate
      that circulating ALT activity is negatively associated with adiponectin
      concentration, gamma-GTP is positively associated with increased IL-6
      concentration, and AST is not associated with these cytokines in middle-aged
      Japanese men not being treated for metabolic diseases.

PMID- 22472284
TI  - An evaluation of protein intake for metabolic demands and the quality of dietary
      protein in rats using an indicator amino acid oxidation method.
AB  - Currently, protein requirements are generally determined based on nitrogen
      balance studies, but there are a variety of limitations associated with this
      method. The indicator amino acid oxidation (IAAO) method, with a theoretical base
      that differs widely from the nitrogen balance method, was developed as an
      alternative method for humans. The objective of the present study was to evaluate
      protein intakes for metabolic demands and protein quality, using protein itself,
      in rats employing the IAAO technique with L-[1-(13)C]phenylalanine. Male
      Wistar/ST rats (5-6 wk old) received a graded casein (4.3, 8.6, 12.9, 17.2, 21.5,
      25.8%), or a wheat gluten (7.2, 10.8, 14.4, 18.0, 21.6, 25.2%) diet, along with L
      [1-(13)C]phenylalanine. An isotopic plateau in breath was achieved 210 min after
      the start of the (13)C ingestion. The protein intakes for metabolic demands were
      calculated by applying a mixed-effect change-point regression model to breath
      (13)CO(2) data, which identified a breakpoint at minimal breath (13)CO(2) in
      response to graded protein intake. The protein intakes for metabolic demands
      determined by the IAAO method were 13.1 g/kg BW/d for casein and 18.1 g/kg BW/d
      for wheat gluten, showing a tendency similar to that determined by the nitrogen
      balance method. These results demonstrated that the IAAO method could be employed
      to evaluate not only the protein intakes for metabolic demands, but the dietary
      protein quality in freely living rats, suggesting that this method might be
      viable in a clinical setting.

PMID- 22472286
TI  - Loss of vitamin B(12) in fish (round herring) meats during various cooking
      treatments.
AB  - The loss of vitamin B(12) in round herring meats during various cooking
      treatments was evaluated. Although amounts of vitamin B(12) were three times
      greater in the viscera (37.5 +/- 10.6 ug/100 g fresh weight) than in the meats,
      about 73% of total vitamin B(12) found in the whole fish body (except for head
      and bones) were recovered in the meats (5.1 +/- 1.0 ug of vitamin B(12)). The
      vitamin B(12) contents of the round herring's meats were significantly decreased
      up to ~62% during cooking by grilling, boiling, frying, steaming, and
      microwaving. There was, however, no loss of vitamin B(12) during vacuum-packed
      pouch cooking. Model experiment using hydroxocobalamin suggest that loss of
      vitamin B(12) is dependent on the degree of temperature and time used in
      conventional cooking, and is further affected by the concomitant ingredients of
      food. Retention of vitamin B(12) was not dependent on vacuum or temperature (or
      both) used in the vacuum-packed pouch cooking.

PMID- 22472285
TI  - beta-cryptoxanthin suppresses the adipogenesis of 3T3-L1 cells via RAR
      activation.
AB  - We recently reported that the oral intake of beta-cryptoxanthin exerted anti
      obesity effects by lowering visceral fat levels. In the present study, we
      characterized the molecular mechanisms underlying the lipid-lowering effects of
      beta-cryptoxanthin on 3T3-L1 cells. Consistent with our previous findings, beta
      cryptoxanthin rapidly reduced the level of intracellular lipids in 3T3-L1 cells
      as assessed by Oil red O staining. Using an in vitro nuclear receptor binding
      assay, we demonstrated the ability of beta-cryptoxanthin to bind to and activate
      members of the retinoic acid receptor (RAR) family. Accordingly, treatment of
      cells with LE540, an RAR antagonist, abolished the beta-cryptoxanthin-dependent
      suppression of 3T3-L1 adipogenesis, suggesting that beta-cryptoxanthin mediates
      its effects on 3T3-L1 cells via RAR activation. In addition, real-time RT-PCR
      analysis revealed that beta-cryptoxanthin down-regulates mRNA expression of
      PPARgamma, a key regulator of adipocyte differentiation, and that this inhibition
      was blocked by LE540 treatment. Taken together, these data indicate that RAR
      activation contributes to the molecular mechanism by which beta-cryptoxanthin
      prevents obesity.

PMID- 22472287
TI  - Biotin, niacin, and pantothenic acid assay using lyophilized lactobacillus
      plantarum ATCC 8014.
AB  - The purpose of this study was to improve the efficiency of the microbiological
      assays for biotin, niacin, and pantothenic acid by using lyophilized cells from
      Lactobacillus plantarum ATCC 8014. The use of lyophilized cells as an inoculum
      was assessed to avoid time-consuming processes like cell precultivation and
      washing. The authors also examined the effects of various protectants such as
      skim milk, sucrose, sorbitol, and trehalose on the assay. The viable cell counts
      of the lyophilized cells were found to be approximately equal for different
      protectants. The standard curves for biotin, niacin, and pantothenic acid
      concentrations obtained using lyophilized cells with sucrose and intact cells
      gave similar linear ranges. Furthermore, the measured vitamin concentrations of
      the standard reference material 3280 were in the range of the established values.
      Therefore, lyophilized cells with sucrose are potential alternative inocula for
      the turbidimetric method. This will increase the overall convenience associated
      with microbiological assays.

PMID- 22472288
TI  - Extracts of common buckwheat bran prevent sucrose digestion.
AB  - Buckwheat has been shown to have various health benefits such as reduction of
      hypertension and improvement of hypercholesterolemia; however, its effect on
      diabetes has not been fully elucidated. In this study, buckwheat bran extracts
      (BBE) inhibited sucrase activity in vitro more effectively than buckwheat. Balb/c
      mice pretreated with BBE showed dose-dependent reductions of blood glucose,
      greater than those observed with control mice, within 60 min following oral
      sucrose administration. Blood glucose levels in mice pretreated with buckwheat
      extracts were also significantly lower compared to those in control mice within
      30 min following oral administration of sucrose. However, rutin, one of the
      abundant polyphenols of BBE, did not lower blood glucose level. Our data indicate
      that components of BBE other than rutin have inhibitory activity against sucrase
      in vivo. These results suggest that BBE could have beneficial effects on
      diabetes.

PMID- 22472289
TI  - Longitudinal, cross-cohort comparison of physical activity patterns in Chinese
      mothers and children.
AB  - BACKGROUND: There is limited evidence comparing adult and child physical activity
      (PA) trends and examining parent-child PA associations within a newly
      industrialized country setting. PA research within a newly industrialized country
      setting is particularly important given the negative effects of rapid
      urbanization, socioeconomic growth, and technological advances on PA behaviors.
      The purpose of our study was to examine trends and associations in PA behaviors
      in Chinese mother-child pairs and to investigate relationships between PA
      behaviors and socioeconomic variables in this dyad. METHODS: We studied PA
      behaviors in 2 separate cohorts of mother-child pairs (n = 353) followed over a 2
      4 year time period using longitudinal data from the China Health and Nutrition
      Survey (2000 COHORT: 2000-2004; 2004 COHORT: 2004-2006). Comparable mother-child
      PA behaviors included total metabolic equivalent hours per week (MET-hrs/wk) from
      active commuting, leisure-time sports, and sedentary behaviors. Logistic
      regression models were used to examine associations between mother and child PA
      and relationships between PA behaviors and socioeconomic variables. RESULTS:
      Children experienced increases in active commuting and leisure-time sports
      activities with increasing child age, whereas mothers experienced temporal
      declines in active commuting and minimal change in leisure-time sports activity.
      Sedentary behavior was high for children and mothers over time. Mother-child
      associations were positive for active commuting and leisure-time sports
      activities and negative for sedentary behavior (P < 0.05). Maternal education was
      associated with a greater likelihood of high leisure-time sports activity and
      high sedentary behavior in mothers but not in children (P < 0.05). CONCLUSION:
      Efforts to reduce sedentary behavior in Chinese mothers and children are
      imperative. While increased leisure-time and active commuting activities in
      children is encouraging, continued PA promotion in children and more intensive
      efforts to promote leisure-time sports and active commuting in mothers is needed.

PMID- 22472291
TI  - The politics behind the implementation of the WTO Paragraph 6 Decision in Canada
      to increase global drug access.
AB  - BACKGROUND: The reform of pharmaceutical policy can often involve trade-offs
      between competing social and commercial goals. Canada's Access to Medicines
      Regime (CAMR), a legislative amendment that permits compulsory licensing for the
      production and export of medicines to developing countries, aimed to reconcile
      these goals. Since it was passed in 2004, only two orders of antiretroviral
      drugs, enough for 21,000 HIV/AIDS patients in Rwanda have been exported. Future
      use of the regime appears unlikely. This research aimed to examine the politics
      of CAMR. METHODS: Parliamentary Committee hearing transcripts from CAMR's
      legislative development (2004) and legislative review (2007) were analysed using
      a content analysis technique to identify how stakeholders who participated in the
      debates framed the issues. These findings were subsequently analysed using a
      framework of framing, institutions and interests to determine how these three
      dimensions shaped CAMR. RESULTS: In 2004, policy debates in Canada were dominated
      by two themes: intellectual property rights and the TRIPS Agreement. The right to
      medicines as a basic human right and CAMR's potential impact on innovation were
      hardly discussed. With the Departments of Industry Canada and International Trade
      as the lead institutions, the goals of protecting intellectual property and
      ensuring good trade relations with the United States appear to have taken
      priority over encouraging generic competition to achieve drug affordability. The
      result was a more limited interpretation of patent flexibilities under the WTO
      Paragraph 6 Decision. The most striking finding is the minimal discussion over
      the potential barriers developing country beneficiaries might face when
      attempting to use compulsory licensing, including their reluctance to use TRIPS
      flexibilities, their desire to pursue technological development and the
      constraints inherent in the WTO Paragraph 6 Decision. Instead, these issues were
      raised in 2007, which can be partly accounted for by experience in implementing
      the legislation and hence a greater representation of the interests of potential
      beneficiary country governments. CONCLUSIONS: The Canadian Government designed
      CAMR as a last resort measure. Increased input from the developing country
      beneficiaries and shifting to institutions where the right to health gets
      prioritized may lead to policies that better achieves affordable drug access.

PMID- 22472290
TI  - Hexavalent chromium Cr(VI) up-regulates COX-2 expression through an NFkappaB/c
      Jun/AP-1-dependent pathway.
AB  - BACKGROUND: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via
      inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are
      not well understood. OBJECTIVES: We evaluated cyclooxygenase-2 (COX-2) expression
      and the signaling pathway leading to this induction due to Cr(VI) exposure in
      cultured cells. METHODS: We used the luciferase reporter assay and Western
      blotting to determine COX-2 induction by Cr(VI). We used dominant negative
      mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation
      approaches to elucidate the signaling pathway leading to COX-2 induction.
      RESULTS: We found that Cr(VI) exposure induced COX-2 expression in both normal
      human bronchial epithelial cells and mouse embryonic fibroblasts in a
      concentration- and time-dependent manner. Deletion of IKKbeta [inhibitor of
      transcription factor NFkappaB (IkappaB) kinase beta; an upstream kinase
      responsible for nuclear factor kappaB (NFkappaB) activation] or overexpression of
      TAM67 (a dominant-negative mutant of c-Jun) dramatically inhibited the COX-2
      induction due to Cr(VI), suggesting that both NFkappaB and c-Jun/AP-1 pathways
      were required for Cr(VI)-induced COX-2 expression. Our results show that p65 and
      c-Jun are two major components involved in NFkappaB and AP-1 activation,
      respectively. Moreover, our studies suggest crosstalk between NFkappaB and c
      Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction.
      CONCLUSION: We demonstrate for the first time that Cr(VI) is able to induce COX-2
      expression via an NFkappaB/c-Jun/AP-1-dependent pathway. Our results provide
      novel insight into the molecular mechanisms linking Cr(VI) exposure to lung
      inflammation and carcinogenesis.

PMID- 22472292
TI  - Effects of cobalt chloride on nitric oxide and cytokines/chemokines production in
      microglia.
AB  - The involvement of microglial activation in metal neurotoxicity is becoming
      increasingly recognized. Some metal ions, such as zinc (II) and manganese (II),
      have been recently reported as microglial activators to induce the release of
      inflammatory mediators including cytokines, chemokines and nitric oxide (NO)
      which are involved in the pathogenesis of neurological diseases. Cobalt is
      essential for human life. However, excessive cobalt is cytotoxic and neurotoxic.
      In the present study, we determined cobalt-induced production of NO and
      cytokines/chemokines in N9 cells, a murine microglial cell line. High levels of
      cobalt significantly up-regulated iNOS mRNA and protein expression, which
      resulted in the release of NO. Cobalt induced the production of tumor necrosis
      factor alpha (TNF-alpha) and interleukin-6 (IL-6) in a concentration- and time
      dependent manner in both N9 cells and primary mouse microglia and increased
      lipopolysaccharides (LPS)-induced cytokine production. Further study showed that
      cobalt induced cytokine production by a mechanism involving both nuclear factor
      kappa B (NF-kappaB) and p38 mitogen-activated protein kinase (MAPK) signaling
      pathways. The involvement of reactive oxygen species (ROS) in microglial
      activation was also confirmed. These findings suggested that cobalt neurotoxicity
      should be attributed not only directly to neuronal damage but also indirectly to
      microglial activation which might potentiate neuronal injury via elevation of
      proinflammatory mediator levels.

PMID- 22472293
TI  - Recurrent urethrovesical anastomotic strictures following artificial urinary
      sphincter implantation: a case report.
AB  - INTRODUCTION: The management of an anastomotic stricture after a radical
      prostatectomy can become a complex and difficult situation when an artificial
      urinary sphincter precedes the formation of the stricture. The urethral narrowing
      does not allow the passage of the routinely used urological instruments and no
      previous reports have suggested alternate approaches. CASE PRESENTATION: We
      present the case of a 68-year-old Greek man diagnosed as having a recurrent
      anastomotic stricture approximately two years after a radical prostatectomy and
      three years after the implantation of an artificial urinary sphincter, and
      propose novel alternate methods of treatment. Our patient was first subjected to
      stricture incision with the use of a rigid ureteroscope with a holmium:yttrium
      aluminium-garnet laser fiber, which was followed by a second successful attempt
      with the use of a pediatric resectoscope. After a one-year follow-up, our patient
      is doing well, with no evidence of recurrence. CONCLUSIONS: To the best of our
      knowledge, this is the first report of the management of recurrent urethral
      strictures following an artificial urinary sphincter implantation. Minimal
      invasive techniques with the use of small caliber instruments may offer efficient
      treatment options, diminishing the danger of urethral corrosion.

PMID- 22472294
TI  - The Anticoagulation of Calf Thrombosis (ACT) project: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Half of all lower limb deep vein thrombi (DVT) in symptomatic
      ambulatory patients are located in the distal (calf) veins. While proximal
      disease warrants therapeutic anticoagulation to reduce the associated risks,
      distal DVT often goes untreated. However, a proportion of untreated distal
      disease will undoubtedly propagate or embolize. Concern also exists that
      untreated disease could lead to long-term post thrombotic changes. Currently, it
      is not possible to predict which distal thrombi will develop such complications.
      Whether these potential risks outweigh those associated with unrestricted
      anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT)
      trial aims to compare therapeutic anticoagulation against conservative management
      for patients with acute symptomatic distal deep vein thrombosis. METHODS: ACT is
      a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed
      with acute distal DVT will be allocated to either therapeutic anticoagulation or
      conservative management. All patients will undergo 3 months of clinical and
      assessor blinded sonographic follow-up, followed by 2-year final review. The
      project will commence initially as an external pilot study, recruiting over a 16
      month period at a single center to assess feasibility measures and clinical event
      rates. Primary outcome measures will assess feasibility endpoints. Secondary
      clinical outcomes will be collected to gather accurate data for the design of a
      definitive clinical trial and will include: (1) a composite endpoint combining
      thrombus propagation to the popliteal vein or above, development of symptomatic
      pulmonary embolism or sudden death attributable to venous thromboembolic disease;
      (2) the incidence of major and minor bleeding episodes; (3) the incidence of post
      thrombotic leg syndrome at 2 years using a validated screening tool; and (4) the
      incidence of venous thromboembolism (VTE) recurrence at 2 years. DISCUSSION: The
      ACT trial will explore the feasibility of comparing therapeutic anticoagulation
      to conservative management in acute distal DVT, within a modern cohort. We also
      aim to provide contemporary data on clot propagation, bleeding rates and long
      term outcomes within both groups. These results will inform the conduct of a
      definitive study if feasibility is established.

PMID- 22472295
TI  - Measured and perceived environmental characteristics are related to accelerometer
      defined physical activity in older adults.
AB  - BACKGROUND: Few studies have investigated both the self-perceived and measured
      environment with objectively determined physical activity in older adults.
      Accordingly, the aim of this study was to examine measured and perceived
      environmental associations with physical activity of older adults residing across
      different neighborhood types. METHODS: One-hundred and forty-eight older
      individuals, mean age 64.3 +/- 8.4, were randomly recruited from one of four
      neighborhoods that were pre-determined as either having high- or low walkable
      characteristics. Individual residences were geocoded and 200 m network buffers
      established. Both objective environment audit, and self-perceived environmental
      measures were collected, in conjunction with accelerometer derived physical
      activity behavior. Using both perceived and objective environment data, analysis
      consisted of a macro-level comparison of physical activity levels across
      neighborhood, and a micro-level analysis of individual environmental predictors
      of physical activity levels. RESULTS: Individuals residing in high-walkable
      neighborhoods on average engaged in 11 min of moderate to vigorous physical
      activity per day more than individuals residing in low-walkable neighborhoods.
      Both measured access to non-residential destinations (b = .11, p < .001) and self
      perceived access to non-residential uses (b = 2.89, p = .031) were significant
      predictors of time spent in moderate to vigorous physical activity. Other
      environmental variables significantly predicting components of physical activity
      behavior included presence of measured neighborhood crime signage (b = .4785, p =
      .031), measured street safety (b = 26.8, p = .006), and perceived neighborhood
      satisfaction (b = .5.8, p = .003). CONCLUSIONS: Older adult residents who live in
      high-walkable neighborhoods, who have easy and close access to nonresidential
      destinations, have lower social dysfunction pertinent to crime, and generally
      perceive the neighborhood to a higher overall satisfaction are likely to engage
      in higher levels of physical activity behavior. Efforts aimed at promoting more
      walkable neighborhoods could influence activity levels in older adults.

PMID- 22472296
TI  - Periodontal status of HIV-infected patients undergoing antiretroviral therapy
      compared to HIV-therapy naive patients: a case control study.
AB  - BACKGROUND: Although severe oral opportunistic infections decreased with the
      implementation of highly active antiretroviral therapy, periodontitis is still a
      commonly described problem in patients infected with human immunodeficiency virus
      (HIV). The objective of the present investigation was to determine possible
      differences in periodontal parameters between antiretroviral treated and
      untreated patients. METHODS: The study population comprised 80 patients infected
      with HIV divided into two groups. The first group was receiving antiretroviral
      therapy while the second group was therapy naive. The following parameters were
      examined: probing pocket depth, gingival recession, clinical attachment level,
      papilla bleeding score, periodontal screening index and the index for decayed,
      missed and filled teeth. A questionnaire concerning oral hygiene, dental care and
      smoking habits was filled out by the patients. RESULTS: There were no significant
      differences regarding the periodontal parameters between the groups except in the
      clinical marker for inflammation, the papilla bleeding score, which was twice as
      high (P < 0.0001) in the antiretroviral untreated group (0.58 +/- 0.40 versus
      1.02 +/- 0.59). The participants of this investigation generally showed a
      prevalence of periodontitis comparable to that in healthy subjects. The results
      of the questionnaire were comparable between the two groups. CONCLUSION: There is
      no indication for advanced periodontal damage in HIV-infected versus non-infected
      patients in comparable age groups. Due to their immunodeficiency, HIV-infected
      patients should be monitored closely to prevent irreversible periodontal damage.
      Periodontal monitoring and early therapy is recommended independent of an
      indication for highly active antiretroviral therapy.

PMID- 22472297
TI  - Immature platelet fraction as marker for platelet recovery after stem cell
      transplantation in children.
AB  - OBJECTIVES: Thrombocytopenia occurs in pediatric patients after SCT and has to be
      treated with platelet transfusions which bear certain risks and represent a
      significant cost factor. Monitoring immature platelet (IPF) fraction has been
      proposed to predict platelet recovery thereby reducing the need for transfusions.
      DESIGN AND METHODS: Hematological parameters including IPF were systematically
      studied in 17 pediatric patients after either peripheral blood or bone marrow
      stem cell transplantation. RESULTS: Time to platelet recovery depended on the
      source of stem cells while no differences were detected between percentaged IPF
      peak concentration and time between IPF peak concentration and platelet recovery
      between the groups. Correlation between the timepoints of percentaged IPF peak
      and platelet recovery was high but large interindividual differences were
      observed concerning the duration of this period. In addition, in some patients
      high IPF concentrations were not followed by platelet recovery. CONCLUSIONS:
      Although in general high IPF concentrations are followed by platelet recovery
      wide interindividual variations exist and even no recovery was recorded in four
      patients. As the latter children are not readily identifiable beforehand IPF
      should not be used to omit platelet transfusions.

PMID- 22472298
TI  - Aeromonas hydrophila subsp. dhakensis isolated from feces, water and fish in
      Mediterranean Spain.
AB  - Eight Aeromonas hydrophila-like arabinose-negative isolates from diverse sources
      (i.e., river freshwater, cooling-system water pond, diseased wild European eels,
      and human stools) sampled in Valencia (Spain) during 2004-2005, were
      characterized by 16S rRNA gene sequencing and extensive biochemical testing along
      with reference strains of most Aeromonas species. These isolates and all
      reference strains of A. hydrophila subsp. dhakensis and A. aquariorum showed a
      16S rRNA sequence similarity of 99.8-100%, and they all shared an identical
      phenotype. This matched exactly with that of A. hydrophila subsp. dhakensis since
      all strains displayed positive responses to the Voges-Prokauer test and to the
      use of dl-lactate. This is the first report of A. hydrophila subsp. dhakensis
      recovered from environmental samples, and further, from its original isolation in
      India during 1993-1994. This was accurately identified and segregated from other
      clinical aeromonads (A. hydrophila subsp. hydrophila, A. caviae, A. veronii
      biovars veronii and sobria, A. trota, A. schubertii and A. jandaei) by using
      biochemical key tests. The API 20 E profile for all strains included in A.
      hydrophila subsp. dhakensis was 7047125. The prevalence of this species in
      Spanish sources was higher for water (9.4%) than for feces (6%) or eels (1.3%).
      Isolates recovered as pure cultures from diseased eels were moderately virulent
      (LD(50) of 3.3*10(6) CFU fish(-1)) to challenged eels in experimental trials.
      They were all resistant to ticarcillin, amoxicillin-clavuranic acid, cefoxitin,
      and imipenem, regardless of its source. Our data point to A. hydrophila subsp.
      dhakensis as an emerging pathogen for humans and fish in temperate countries.

PMID- 22472299
TI  - Tuning characteristics of ocular and cervical vestibular evoked myogenic
      potentials in intact and dehiscent ears.
AB  - Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) to
      air-conducted tone bursts (250-2000 Hz) were recorded in 14 patients with
      superior canal dehiscence (SCD) and 32 healthy controls. For cVEMPs, the most
      common 'optimal frequency' in control ears (48.2%) was 500 Hz; for oVEMPs, it was
      1000 Hz (51.8%). We found a significant interaction between age and frequency,
      with a shift towards higher-frequency tuning in older subjects. cVEMP and oVEMP
      tuning in SCD was characterised by a broadening of amplitude and threshold tuning
      curves. The tendency of cVEMPs to tune to lower frequencies compared to oVEMP was
      enhanced in SCD. Differences in cVEMP and oVEMP 'optimal frequencies',
      demonstrated in 57.1% intact ears and 81.3% dehiscent ears, imply differences in
      the recruitment of hair cells generating these two reflexes. Age-matched oVEMP
      amplitudes provided excellent separation between SCD and control ears. Although
      cVEMP amplitudes overlapped between SCD and control ears, better separation was
      achieved by using a 2-kHz stimulus.

PMID- 22472300
TI  - Food labels for consumers, motivated or otherwise.

PMID- 22472301
TI  - Food labelling and dietary behaviour: bridging the gap.

PMID- 22472302
TI  - Understanding differences in the body burden-age relationships of bioaccumulating
      contaminants based on population cross sections versus individuals.
AB  - BACKGROUND: Body burdens of persistent bioaccumulative contaminants estimated
      from the cross-sectional biomonitoring of human populations are often plotted
      against age. Such relationships have previously been assumed to reflect the role
      of age in bioaccumulation. OBJECTIVES: We used a mechanistic modeling approach to
      reproduce concentration-versus-age relationships and investigate factors that
      influence them. METHOD: CoZMoMAN is an environmental fate and human food chain
      bioaccumulation model that estimates time trends in human body burdens in
      response to time-variant environmental emissions. Trends of polychlorinated
      biphenyl (PCB) congener 153 concentrations versus age for population cross
      sections were estimated using simulated longitudinal data for individual women
      born at different times. The model was also used to probe the influence of
      partitioning and degradation properties, length of emissions, and model
      assumptions regarding lipid content and liver metabolism on concentration-age
      trends of bioaccumulative and persistent contaminants. RESULTS: Body burden-age
      relationships for population cross sections and individuals over time are not
      equivalent. The time lapse between the peak in emissions and sample collection
      for biomonitoring is the most influential factor controlling the shape of
      concentration-age trends for chemicals with human metabolic half-lives longer
      than 1 year. Differences in observed concentration-age trends for PCBs and
      polybrominated diphenyl ethers are consistent with differences in emission time
      trends and human metabolic half-lives. CONCLUSIONS: Bioaccumulation does not
      monotonically increase with age. Our model suggests that the main predictors of
      cross-sectional body burden trends with age are the amount of time elapsed after
      peak emissions and the human metabolic and environmental degradation rates.

PMID- 22472303
TI  - Adipose-derived stromal cell therapy improves cardiac function after coronary
      occlusion in rats.
AB  - Recent studies have identified adipose tissue as a new source of mesenchymal stem
      cells for therapy. The purpose of this study was to investigate the therapy with
      adipose-derived stromal cells (ASCs) in a rat model of healed myocardial
      infarction (MI). ASCs from inguinal subcutaneous  adipose tissue of male Wistar
      rats were isolated by enzymatic digestion and filtration. Cells were then
      cultured until passage 3. Four weeks after ligation of the left coronary artery
      of female rats, a suspension of either 100 ul with phosphate-buffered saline
      (PBS) + Matrigel + 2 *  10(6) ASCs labeled with Hoechst (n = 11) or 100 ul of PBS
      + Matrigel (n = 10) was injected along the borders of the ventricular wall scar
      tissue. A sham-operated group (n = 5) was submitted to the same surgical
      procedure except permanent ligation of left  coronary artery. Cardiac performance
      was assessed by electro- and echocardiogram. Echo was performed prior to
      injections (baseline, BL) and 6 weeks after injections (follow-up, FU), and
      values after treatment were normalized by values obtained before treatment.
      Hemodynamic measurements were  performed 6 weeks after injections. All infarcted
      animals exhibited cardiac function impairment. Ejection fraction (EF), shortening
      fractional area (SFA), and left ventricular akinesia (LVA) were similar between
      infarcted groups before treatment. Six weeks after therapy, ASC group showed
      significant  improvement in all three ECHO indices in comparison to vehicle
      group. In anesthetized animals dp/dt(+) was also significantly higher in ASCs
      when compared to vehicle. In agreement with functional improvement, scar area was
      diminished in the ASC group. We conclude that ASCs improve  cardiac function in
      infarcted rats when administered directly to the myocardium.

PMID- 22472304
TI  - Synthesis of silica particles and their application as supports for alcohol
      dehydrogenases and cofactor immobilizations: conformational changes that lead to
      switch in enzyme stereoselectivity.
AB  - FTIR, circular dichroism (CD) and fluorescence spectroscopies were used to
      characterize conformational changes in horse liver alcohol dehydrogenase (HLADH)
      and ketoreductase (KRED 117) upon physical and covalent immobilizations on silica
      particles (functionalized with amino, epoxy and thiol groups) of different sizes.
      Conformational changes for immobilized enzymes were associated with high and low
      frequency shifts of the amide I and II bands. CD spectra of native HLADH and KRED
      117 characterized with a negative peak at 222nm indicating a alpha-helical
      structure. The disappearance of the negative peak in the CD spectra of
      immobilized enzymes and appearance of a positive peak at 222nm supported these
      observations. These findings demonstrated unfolding of folded enzymes and
      exposure of the amino acid residues during denaturation with a red shift in
      tryptophan fluorescence. The decrease in specific activities (by 60-70% in all
      cases) for both immobilized enzymes was correlated to those of conformational
      changes. Silica-attached enzyme-NADH systems were evaluated for enantioselective
      reduction of 1-(p-methoxyphenyl)-propan-2-one. Conformational changes enhanced
      the enantioselectivity of immobilized HLADH with a switch in its
      stereoselectivity. In the case of immobilized KRED 117, kinetic values (V(max)
      and K(m)) were lower than that of the free enzyme, without enhancing enzyme
      enantio- and stereoselectivity.

PMID- 22472305
TI  - A proposal to standardize reporting units for fecal immunochemical tests for
      hemoglobin.
AB  - Fecal immunochemical tests for hemoglobin are replacing traditional guaiac fecal
      occult blood tests in population screening programs for many reasons. However,
      the many available fecal immunochemical test devices use a range of sampling
      methods, differ with regard to hemoglobin stability, and report hemoglobin
      concentrations in different ways. The methods for sampling, the mass of feces
      collected, and the volume and characteristics of the buffer used in the sampling
      device also vary among fecal immunochemical tests, making comparisons of test
      performance characteristics difficult. Fecal immunochemical test results may be
      expressed as the hemoglobin concentration in the sampling device buffer and,
      sometimes, albeit rarely, as the hemoglobin concentration per mass of feces. The
      current lack of consistency in units for reporting hemoglobin concentration is
      particularly problematic because apparently similar hemoglobin concentrations
      obtained with different devices can lead to very different clinical
      interpretations. Consistent adoption of an internationally accepted method for
      reporting results would facilitate comparisons of outcomes from these tests. We
      propose a simple strategy for reporting fecal hemoglobin concentration that will
      facilitate the comparison of results between fecal immunochemical test devices
      and across clinical studies. Such reporting is readily achieved by defining the
      mass of feces sampled and the volume of sample buffer (with confidence intervals)
      and expressing results as micrograms of hemoglobin per gram of feces. We propose
      that manufacturers of fecal immunochemical tests provide this information and
      that the authors of research articles, guidelines, and policy articles, as well
      as pathology services and regulatory bodies, adopt this metric when reporting
      fecal immunochemical test results.

PMID- 22472306
TI  - Re: potential pitfalls of crossover and thoughts on iniparib in triple-negative
      breast cancer.

PMID- 22472307
TI  - Is 15-LOX-1 a tumor suppressor?

PMID- 22472308
TI  - Effects of gut-targeted 15-LOX-1 transgene expression on colonic tumorigenesis in
      mice.
AB  - Expression of 15-lipoxygenase-1 (15-LOX-1) is decreased in many human cancers;
      however, the mechanistic significance of its decreased expression has been
      difficult to determine because its mouse homolog 12/15-LOX has opposing
      functions. We generated a mouse model in which expression of a human 15-LOX-1
      transgene was targeted to the intestinal epithelium via the villin promoter.
      Targeted expression was confirmed by real-time reverse transcription-polymerase
      chain reaction and immunoblotting. When the 15-LOX-1 transgene was expressed in
      colonic epithelial cells of two independent mouse lines (B6 and FVB),
      azoxymethane-inducible colonic tumorigenesis was suppressed (mean number of
      tumors: wild type [WT] = 8.2, 15-LOX-1(+/-) = 4.91, 15-LOX-1(+/+) = 3.57; WT vs
      15-LOX-1(+/-) two-sided P = .003, WT vs 15-LOX-1(+/+) two-sided P < .001; n = 10
      14 mice per group). 15-LOX-1 transgene expression was always decreased in the
      tumors that did develop. In the presence of expression of the 15-LOX-1 transgene,
      expression of tumor necrosis factor alpha and its target inducible nitric oxide
      synthase were decreased and activation of nuclear factor-kappa B in colonic
      epithelial cells was inhibited.

PMID- 22472309
TI  - Twin pregnancy with complete hydatidiform mole and coexisting fetus following
      ovulation induction with a non-prescribed clomiphene citrate regimen: a case
      report.
AB  - INTRODUCTION: Twin pregnancy with complete hydatidiform mole represents a very
      rare obstetric problem. Management of such cases is always problematic because
      the possibility of fetal survival should always be weighed against the risk of
      complications of molar pregnancy. CASE PRESENTATION: A 34-year-old Caucasian
      woman presented to our center with mild vaginal bleeding. Our patient was 16
      weeks pregnant after a seven-year period of primary infertility. She became
      pregnant following a non-prescribed regimen of clomiphene citrate extending from
      the second day to the 13th day of her last cycle. A transabdominal ultrasound
      examination revealed a twin pregnancy with complete hydatidiform mole and a
      coexisting fetus. Serum beta human chorionic gonadotropin was falsely low as
      identified by serial dilution of the sample (the 'hook effect'). Our patient
      refused termination of pregnancy and she was hospitalized for strict observation
      and follow-up. Unfortunately, she developed an attack of severe vaginal bleeding
      and a hysterotomy was performed. The fetus died shortly after birth. CONCLUSIONS:
      Twin pregnancy with complete hydatidiform mole represents a matter of
      controversy. We suggest that conservation should always be considered whenever
      tertiary care services and strict observation are available.

PMID- 22472310
TI  - Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons
      for treatment of early psychosis.
AB  - Hyperprolactinaemia is a common side effect of antipsychotics; markedly raised
      levels are less common. Higher levels of prolactin result from longer exposure to
      higher doses, especially with older antipsychotics or with risperidone, sulpiride
      or amisulpride. Galactorrhoea, gynaecomastia, menstrual abnormalities and sexual
      dysfunction including hypogonadism and fertility problems are consequences of
      raised prolactin, and in the longer-term bone demineralisation. Younger patients
      may be more susceptible to hyperprolactinaemia. Trial reports often fail to state
      the frequency of raised levels.

PMID- 22472311
TI  - The metabolic syndrome in schizophrenia: is inflammation a contributing cause?
AB  - This non-systematic review of the literature summarizes the evidence that
      inflammation plays a major role in the psychopathology of schizophrenia and in
      the mechanisms that contribute to physical ill health that is commonly associated
      with schizophrenia. The impact of prenatal infections on the developing brain,
      the possible genetic link between the human lymphocyte antigen gene,
      inflammation, heart disease and diabetes, together with the increase in pro
      inflammatory cytokines in the blood and cerebrospinal fluid provide convincing
      evidence that inflammation is a major factor in the pathology of this disorder.
      The changes in immune-related markers and specific neurotransmitters associated
      with the positive symptoms of schizophrenia are described. In addition, the
      possible mechanism whereby structural changes occur in the brain is associated
      with the neurotoxic effects of pro-inflammatory cytokines, together with the
      neurotoxic metabolites from the tryptophan-kynurenine pathway that is activated
      by pro-inflammatory cytokines, is also discussed. The role of effective
      antipsychotic drug treatment in attenuating the inflammatory response is
      described. However, evidence is limited regarding the causal connection between
      atypical antipsychotic drugs and the changes in glucose and lipid metabolism that
      could trigger the onset of physical ill health, including diabetes and heart
      disease. Indeed, there is evidence that there is a metabolic predisposition to
      diabetes in patients with schizophrenia that is exacerbated by obesity and
      thereby contributes to cardiovascular disease and other co-morbid illnesses. It
      is concluded that the effects of inflammatory mediators on the brain causally
      contribute to the pathology of schizophrenia and the ill health that accompanies
      the disorder.

PMID- 22472312
TI  - A case of acute suicidality following excessive caffeine intake.
AB  - Energy and stimulant drinks which contain caffeine provide enlivening effects,
      reduce fatigue and improve concentration and endurance. However, consumers may
      also experience physical and psychological side effects as a result of excessive
      consumption of caffeine within these drinks. Caffeine is known to exacerbate or
      induce some psychiatric conditions such as anxiety, panic attacks, psychosis and
      mania. Here we discuss a case of acute suicidality following sleep deprivation
      after the excessive consumption of a popular energy drink. We are concerned that
      such widely available stimulant drinks should contain health warnings or advice
      regarding moderating consumption.

PMID- 22472314
TI  - Human-animal anthrax outbreak in the Luangwa valley of Zambia in 2011.
AB  - There has been a reduction of incidences of anthrax in the developed countries
      but it is still a public health problem in the developing countries where
      communities live in interface areas with wildlife. An outbreak of anthrax in
      Hippopotamus amphibious was observed in Zambia. Following the death of
      hippopotamuses, suspected human cases were reported. The objective of this study
      was to isolate and confirm Bacillus anthracis and to determine the antimicrobial
      susceptibility for the management of the disease. Of the specimens collected,
      29.4% (95% confidence interval [CI], 11.4-56.0) were from humans, 42.1% (95% CI,
      21.1-66.0) were from hippopotamuses and 20.0% (95% CI, 6.61-44.3) from the soil
      were found to be positive were for B. anthracis. An antimicrobial susceptibility
      test revealed that all the isolates were found to be sensitive to the recommended
      antibiotics. The disease control was achieved by case management and by
      explaining to the communities that they should avoid contact with animals that
      die from unknown causes.

PMID- 22472315
TI  - Acute coronary syndrome following snake bite: a report of three cases from a
      tertiary care hospital in rural southern India.
AB  - Snake bite is a common cause of preventable death in rural India which is often
      due to neurological complications and coagulopathy. We report on three patients
      who presented with bites and later developed acute coronary syndrome during the
      course of their stay in hospital. Such patients have to be managed conservatively
      because of their coexistent coagulopathy.

PMID- 22472316
TI  - Fetal outcome of antepartum and intrapartum eclampsia in Aba, southeastern
      Nigeria.
AB  - The objective of this study was to evaluate the fetal outcome of antepartum and
      intrapartum eclampsia. All cases of antepartum and intrapartum eclampsia managed
      at the Abia State University Teaching Hospital, Aba, Nigeria, between 1 January
      2002 and 31 December 2007 were retrospectively analysed. Of the women who were
      delivered in our hospital over the period studied, 0.80% had ante- or intrapartum
      eclampsia which started mostly outside the hospital: 85.4% were unbooked; 62.5%
      nulliparous; and 62.5% aged less than 30 years. Forty-eight babies were delivered
      by the eclamptic mothers. All of the fetuses were delivered in the last
      trimester: 68.8% of the fetuses were preterm; and 58.7% had a low birthweight.
      Stillbirths occurred in 60.4%; 8.3% suffered severe birth asphyxia; and 70.9%
      were delivered vaginally. Sustained education of pregnant women on the need for
      early booking and regular antenatal visits is recommended.

PMID- 22472317
TI  - Acute kidney injury in dengue fever using Acute Kidney Injury Network criteria:
      incidence and risk factors.
AB  - The aim of this study was to assess incidence and risk factors for acute kidney
      injury (AKI) in patients with dengue fever (DF). A total of 223 patients (males,
      130; females, 93; mean age, 26.2 +/- 18.2 years) from a tertiary care centre in
      southern India were retrospectively analysed. Acute renal failure (ARF) developed
      in 24 (10.8%) patients. Based on the Acute Kidney Injury Network (AKIN) criteria,
      the results revealed that: 12 (5.4%) had mild AKI; seven (3.1%) had moderate AKI;
      and five (2.2%) had severe AKI. A further 54 (24%) were diagnosed with dengue
      haemorrhagic fever (DHF); 11 (5%) were co-infected with leptospirosis;
      thrombocytopenia was present in 157 (70%); and 64 (29%) were hypotensive.
      Patients were divided into either group A (with AKI) or group B (without AKI),
      and group A was divided into mild (A1), moderate (A2) and severe (A3) subgroups.
      We recorded: a higher total white count (A = 9824; B = 6706; P = 0.01); serum
      glutamic pyruvic transaminase (SGPT; A = 450; B = 144; P = 0.001); alkaline
      phosphatase (ALP) levels (A = 207; B = 42; P = 0.001); lower albumin (A = 2.65; B
      = 3.09; P < 0.001); and serum bicarbonate (A = 20.57; B = 23.21; P = 0.009).
      Hypotension (P = 0.01), coexisting viral hepatitis (P < 0.001), sepsis (P <
      0.001), multiple organ dysfunction syndrome (MODS; P < 0.001) and the need for
      inotropes (P < 0.001) were associated with DF. Total white count (P = 0.038),
      glomerular filtration rate (GFR) on discharge (P = 0.034), specific gravity of
      urine (P = 0.006), ALP (P = 0.013), SGPT (P = 0.042), MODS (P = 0.05) and use of
      platelet fresh frozen plasma (FFP; P = 0.007) were significantly different
      between mild, moderate and severe AKI subgroups. Twenty-two (9%) died. AKI is
      associated with an increased mortality in DF (P = 0.005).

PMID- 22472318
TI  - Scrub typhus and leptospirosis co-infection in Himalayan region.
AB  - Scrub typhus and leptospirosis are both zoonosis and systemic febrile illnesses
      with diverse clinical manifestations and they may present with similar signs and
      symptoms. We present a case of co-infection of scrub typhus and leptospirosis
      from Himachal Pradesh in the Himalayan region of India.

PMID- 22472319
TI  - Ca2+-regulatory proteins in cardiomyocytes from the right ventricle in children
      with congenital heart disease.
AB  - BACKGROUND: Hypoxia and hypertrophy are the most frequent pathophysiological
      consequence of congenital heart disease (CHD) which can induce the alteration of
      Ca2+-regulatory proteins and inhibit cardiac contractility. Few studies have been
      performed to examine Ca2+-regulatory proteins in human cardiomyocytes from the
      hypertrophic right ventricle with or without hypoxia. METHODS: Right ventricle
      tissues were collected from children with tetralogy of Fallot [n = 25, hypoxia
      and hypertrophy group (HH group)], pulmonary stenosis [n = 25, hypertrophy group
      (H group)], or small isolated ventricular septal defect [n = 25, control group (C
      group)] during open-heart surgery. Paraffin sections of tissues were stained with
      3,3'-dioctadecyloxacarbocyanine perchlorate to measure cardiomyocyte size.
      Expression levels of Ca2+-regulatory proteins [sarcoplasmic reticulum Ca2+-ATPase
      (SERCA2a), ryanodine receptor (RyR2), sodiumcalcium exchanger (NCX), sarcolipin
      (SLN) and phospholamban (PLN)] were analysed by means of real-time PCR, western
      blot, or immunofluorescence. Additionally, phosphorylation level of RyR and PLN
      and activity of protein phosphatase (PP1) were evaluated using western blot.
      RESULTS: Mild cardiomyocyte hypertrophy of the right ventricle in H and HH groups
      was confirmed by comparing cardiomyocyte size. A significant reduction of SERCA2a
      in mRNA (P<0.01) was observed in the HH group compared with the C group. The
      level of Ser16-phosphorylated PLN was down-regulated (P<0.01) and PP1 was
      increased (P<0.01) in the HH group compared to that in the C group. CONCLUSIONS:
      The decreased SERCA2a mRNA may be a biomarker of the pathological process in the
      early stage of cyanotic CHD with the hypertrophic right ventricle. A combination
      of hypoxia and hypertrophy can induce the adverse effect of PLN-Ser16
      dephosphorylation. Increased PP1 could result in the decreased PLN-Ser16 and
      inhibition of PP1 is a potential therapeutic target for heart dysfunction in
      pediatrics.

PMID- 22472320
TI  - An immunocompetent migrant presenting with neurosyphilis with an unusual
      unilateral papillitis: a case report.
AB  - Unilateral papillitis caused by Treponema pallidum was found in an
      immunocompetent homosexual patient with severe vision loss who had received
      previous antibiotics treatment. Syphilis-related ocular manifestation is more
      common in the early stages of the disease and it can be associated with a central
      nervous system localization. In this patient, neurosyphilis was diagnosed on the
      basis of clinical and laboratory findings. Optical examination revealed
      unilateral papillitis in the left eye and no relative afferent pupillary defects.
      The patient underwent visual field examinations with conventional perimetry using
      the 30-2 program of the Humphrey Visual Field Analyzer, which indicated a blind
      spot enlargement in the left eye. Optical coherence tomography, visual evoked
      potentials (VEP), and fluorescein angiograms revealed inflammation of the optic
      nerve head with edematous and blurred margins. A reactive T. pallidum
      hemagglutination assay with low rapid plasma reagin (RPR) serum titer was
      performed; an HIV antibody test and MRI of the orbits and head with contrast gave
      negative results. Resolution of the ocular inflammation after intravenous
      penicillin treatment was obtained. The reported case illustrates the importance
      of early recognition of this treatable disease. The rise of syphilis, especially
      in urban areas, necessitates a high level of suspicion when dealing with patients
      with intraocular inflammation of unknown origin. Lues serology should be
      incorporated into routine laboratory diagnostics to aid in the detection of such
      cases. Considering the re-emergence of syphilis, screening of migrants from
      countries with high syphilis seroprevalences should be recommended.

PMID- 22472321
TI  - Predictive model for refractoriness in temporal lobe epilepsy based on clinical
      and diagnostic test data.
AB  - INTRODUCTION: Temporal Lobe Epilepsy (TLE) is frequently resistant to drug
      treatment, but a high percentage of these patients can be free of seizures after
      epilepsy surgery. Delay in the surgical decision has been related to quality of
      life impairment, social and work limitations, and increased mortality risk. A
      predictive model for refractoriness based on clinical and diagnostic factors may
      allow its earlier detection and a shorter delay before surgery. MATERIAL AND
      METHODS: A case-control study was conducted in TLE patients over 16 years old.
      The dependent variable was resistance to medical treatment according to ILAE 2010
      criteria. Independent variables were clinical, semiological, therapeutic,
      neurophysiological, radiological, and neuropsychological variables. A
      multivariate study was conducted to identify the variables associated with
      refractoriness, calculating the positive and negative predictive values and
      positive likelihood ratios of these variables individually and in combination.
      These data were used to construct a refractoriness predictive model. RESULTS:
      ILAE refractoriness criteria were met by 83 patients (50.9%). In the multivariate
      analysis, refractoriness was significantly associated with one semiological
      variable, one neuroradiological variable, one neurophysiological variable, and
      two therapeutic variables but not with neuropsychological test outcomes. These
      significant variables were used to construct a predictive model. CONCLUSION:
      Assessment of semiological, neurophysiological, and neuroradiological data can
      serve to stratify the risk of refractory epilepsy in TLE patients.

PMID- 22472322
TI  - Reversal of pulmonary vascular remodeling in pulmonary hypertensive rats.
AB  - Pulmonary hypertension is responsible for significant mortality and morbidity
      among newborns and infants. The pathology is characterized by pulmonary vascular
      remodeling with medial hypertrophy and adventitial thickening, leading to
      decreased gas exchange. Since it is unknown if these abnormalities are
      reversible, we analyzed these vascular changes in pulmonary hypertensive rats.
      Exposure of rats to hypobaric hypoxia for 4 weeks induced clinical signs of
      pulmonary hypertension, such as increased right ventricular systolic pressure,
      increased right ventricular weight and considerable pulmonary vascular
      remodeling. The vascular changes were associated with the expression of Non 
      Muscle Myosin Heavy Chain B in the pre-acinar vessels and an increased expression
      of alpha Smooth Muscle Actin, Smooth Muscle Myosin Heavy Chain 2 and Calponin in
      the intra-acinar vessels. The right ventricular systolic pressure and right
      ventricular weight gradually decreased after specific periods of recovery in
      normoxia, although this reversal did not reach baseline levels after six weeks at
      normoxia. However, the cellular changes in the pulmonary vasculature were
      completely reversed. Development of pulmonary hypertension is associated with an
      increase of synthetic perivascular cells in the pre-acinar arteries and an
      aberrant differentiation of perivascular cells in the smallest intra-acinar
      arteries. These cellular and structural changes in the pulmonary vasculature are
      completely reversible after recovery in normoxia.

PMID- 22472323
TI  - Epigenetic regulation of GATA4 expression by histone modification in AFP
      producing gastric adenocarcinoma.
AB  - AFP-producing adenocarcinoma is a variant of adenocarcinoma with high malignancy.
      Production of AFP suggests enteroblastic or hepatoid differentiation of cancer
      cells. GATA4 is a key molecule involved in the prenatal development of the
      stomach and liver. GATA4 is epigenetically silenced by hypermethylation of primer
      region in many types of cancers including gastric cancer. The aim of this study
      is to investigate the expression and epigenetic regulation of GATA4 in AFP
      producing adenocarcinoma. Immunohistochemical analysis revealed that GATA4 was
      positive in 3/8 cases of AFP-producing gastric adenocarcinomas and in 28/30 cases
      of common type adenocarcinomas. Epigenetic modification of GATA4 promoter region
      was investigated with 3 AFP-producing and 4 common-type gastric cancer cell
      lines. GATA4 mRNA was detected in 1/3 of AFP-producing and 2/4 of common-type
      gastric cancer cell lines by RT-PCR. Methylation-specific PCR revealed no GATA4
      methylation in any of the AFP-producing gastric cancers, whereas methylation was
      consistent with GATA4 expression in the common-type gastric cancers. Chromatin
      immunoprecipitation assay for AFP-producing gastric cancers revealed that
      histones H3 and H4 were hypoacetylated in the GATA4-negative cells, while they
      were hyperacetylated in the GATA4-positive cells. Treatment with trichostain A,
      an inhibitor for histone deacetylase, induced acetylation of histones H3 and H4,
      and tri-methylation of lysine 4 of histone H3, which was associated with the
      active transcription of GATA4 in GATA4-negative AFP-producing cells. These
      results indicated that histone deacetylation is a silencing mechanism for GATA4
      expression in AFP-producing gastric cancer cells. Differences between AFP
      producing gastric cancer and common-type gastric cancer in terms of the mechanism
      of GATA4 regulation may be reflected in the phenotypic deviation of AFP-producing
      gastric cancer from common-type gastric cancer.

PMID- 22472324
TI  - Time to initiation of treatment with polymyxin B cartridge hemoperfusion in
      septic shock patients.
AB  - BACKGROUND: We investigated whether early initiation of hemoperfusion with a
      polymyxin B cartridge (PMX) after the diagnosis of septic shock could improve the
      clinical outcome. METHODS: A prospective, open-labeled, multicenter cohort study
      was performed at intensive care units in Japan. 41 patients received PMX within 6
      h after the diagnosis of septic shock (early group) and 51 patients were treated
      after 6 h (late group). RESULTS: The early group had a significantly shorter
      duration of ventilator support and also had a lower catecholamine requirement.
      PMX was effective for improvement of hypotension, hypoperfusion, the sequential
      organ failure assessment score, and pulmonary oxygenation regardless of the
      timing of its initiation. The 28-day mortality rate did not differ between the
      two groups. CONCLUSIONS: Early initiation of PMX shortened the duration of
      ventilator support and also reduced the catecholamine requirement, so early
      treatment of septic shock should achieve a better outcome.

PMID- 22472325
TI  - The greening of pesticide-environment interactions: some personal observations.
AB  - BACKGROUND: Pesticide-environment interactions are bidirectional. The environment
      alters pesticides by metabolism and photodegradation, and pesticides in turn
      change the environment through nontarget or secondary effects. OBJECTIVES:
      Approximately 900 currently used commercial pesticides of widely diverse
      structures act by nearly a hundred mechanisms to control insects, weeds, and
      fungi, usually with minimal disruption of nature's equilibrium. Here I consider
      some aspects of the discovery, development, and use of ecofriendly or green
      pesticides (i.e., pesticides that are safe, effective, and biodegradable with
      minimal adverse secondary effects on the environment). Emphasis is given to
      research in my laboratory. DISCUSSION: The need for understanding and improving
      pesticide-environment interactions began with production of the first major
      insecticide approximately 150 years ago: The arsenical poison Paris Green was
      green in color but definitely not ecofriendly. Development and use of other
      pesticides has led to a variety of problems. Topics considered here include the
      need for high purity [e.g., hexachlorocyclohexane and polychloroborane isomers
      and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)], environmental degradation and
      the bioactivity of resulting photoproducts and metabolites, pesticide
      photochemistry (including the use of structural optimization, photostabilizers,
      and photosensitizers to achieve suitable persistence), the presence of multiple
      active ingredients in botanical insecticides, the need to consider compounds with
      common mechanisms of action, issues related to primary and secondary targets, and
      chemically induced or genetically modified changes in plant biochemistry. Many
      insecticides are bird, fish, and honeybee toxicants, whereas herbicides and
      fungicides pose fewer environmental problems. CONCLUSION: Six factors have
      contributed to the greening of pesticide-environment interactions: advances in
      pesticide chemistry and toxicology, banning of many chlorinated hydrocarbons, the
      development of new biochemical targets, increased reliance on genetically
      modified crops that reduce the amount and variety of pesticides applied, emphasis
      on biodegradability and environmental protection, and integrated pest- and
      pesticide-management systems.

PMID- 22472326
TI  - Meigs' syndrome.

PMID- 22472327
TI  - A climate of safety.

PMID- 22472328
TI  - Planned caesarean hysterectomy versus "conserving" caesarean section in patients
      with placenta accreta.

PMID- 22472329
TI  - Why vaginal breech delivery is an acceptable option.

PMID- 22472330
TI  - A multidisciplinary checklist for management of suspected placenta accreta.
AB  - Rates of abnormally invasive placentation have been escalating. The condition
      requires meticulous planning to ensure safety at delivery. Although placenta
      accreta remains the most common reason for Caesarean hysterectomy in developed
      nations, medical and surgical therapies have allowed fertility preservation. Most
      planning strategies start with risk factor assessment and diagnostic imaging.
      Early planning of arrangements for antepartum and intrapartum management is
      preferable to late planning, when emergency situations are more likely to occur.
      Based on maternal and fetal morbidities, and published evidence of factors that
      may diminish these risks, we have developed a checklist to aid the antepartum and
      intrapartum management of potentially challenging cases of invasive placentation
      or to aid in considering tertiary care consultation and transfer. The proposed
      checklist may best benefit physicians working in primary and secondary levels of
      care in Canada. Ideally, this checklist would be available in electronic form,
      with alerts as needed; a copy of the checklist should be kept in the patient's
      medical chart, with periodic updates.

PMID- 22472331
TI  - Placental location and newborn weight.
AB  - OBJECTIVE: Previous studies suggest that placental location may affect fetal
      growth and the risks of preterm birth and preeclampsia. We studied the
      association between placental location and newborn weight. METHODS: We conducted
      a retrospective cohort study of 796 consecutive singleton births in women who
      delivered at >= 37 weeks' gestation between July and October 2009. We evaluated
      placental location at the time of the second trimester prenatal ultrasound at 16
      to 24 weeks' gestation. Placental location was classified as lateral or
      central/fundal. We assessed the difference in newborn weight according to
      placental location and the incidence of small for gestational age birth weight <
      10th percentile and pregnancy-induced hypertension. Using logistic regression
      analysis, odds ratios were adjusted for maternal age, world region of birth,
      gravidity, parity, maternal weight, history of hypertension or diabetes, current
      smoking or illicit drug use, and infant sex. RESULTS: Among women with lateral
      versus central/fundal placentas, the respective mean (SD) birth weights were 3298
      (550) g and 3352 (579) g (mean difference 54 g, 95% CI 53 to 161; P = 0.32).
      Relative to central/fundal location, laterally located placentas had an adjusted
      OR of 0.81 (95% CI 0.42 to 1.54) for SGA and 0.62 (95% CI 0.18 to 2.10) for
      preeclampsia/gestational hypertension. CONCLUSION: Placental location was not
      associated with differences in newborn weight or other perinatal outcomes.

PMID- 22472332
TI  - The influence of changing post-term induction of labour patterns on severe
      neonatal morbidity.
AB  - OBJECTIVE: To estimate the influence of changing practice patterns of post-term
      induction of labour on severe neonatal morbidity. METHODS: This population-based
      cohort study used data from the Nova Scotia Atlee Perinatal Database to evaluate
      the effect of post-term induction of labour on stillbirth and neonatal mortality
      and severe neonatal morbidity in low-risk pregnancies. The study population
      included all pregnant women >= 40 weeks' gestation delivering in Nova Scotia from
      1988 to 2008 who underwent induction of labour with a single fetus in cephalic
      presentation. Major congenital anomalies and pre-existing or severe gestational
      hypertension and diabetes were excluded. Women delivering post-term from 1994 to
      2008 (after the Post-term Pregnancy Trial) were compared with women delivering
      from 1988 to 1992 to evaluate outcomes with changing maternal characteristics and
      obstetric practice patterns. RESULTS: Evaluation and comparison of time epochs
      (1988 to 1992, 1994 to 1998, 1999 to 2003, and 2004 to 2008) demonstrated an
      increased risk for perinatal mortality or severe neonatal morbidity, especially
      low five-minute Apgar score, among both nulliparous and multiparous women. There
      were no significant differences in the risks for stillbirth or perinatal
      mortality over time. Comparable relationships were demonstrated in a subgroup of
      lower risk women. CONCLUSION: The increase in post-term induction of labour with
      time is associated with a significant increase in severe neonatal morbidity,
      especially among infants born to multiparous women. Evaluation of the antepartum
      and intrapartum management of these low-risk pregnancies may provide additional
      information to reduce morbidity.

PMID- 22472333
TI  - Acute disseminated intravascular coagulation in obstetrics: a tertiary centre
      population review (1980 to 2009).
AB  - OBJECTIVE: To determine the antecedent factors, morbidity, and mortality
      associated with disseminated intravascular coagulation (DIC) in a Nova Scotia
      tertiary maternity hospital over a 30-year period. METHODS: Cases of DIC were
      identified from the Nova Scotia Atlee Perinatal Database for the years 1980 to
      2009 and the hospital charts reviewed. The clinical diagnosis of DIC was
      confirmed or refuted using a combination of the International Society of
      Thrombosis and Haemostasis scoring system and an obstetrical DIC-severity staging
      system. The cause of DIC was determined from chart review. Maternal outcomes
      included massive transfusion (>= 5 units), hysterectomy, admission to ICU, acute
      tubular necrosis (ATN) requiring dialysis, and death. Neonatal outcomes included
      Apgar scores, birth weight, NICU admission, and death. Treatment of DIC was
      assessed by blood products administered, postpartum hemorrhage management, and
      laboratory measurements. RESULTS: There were 49 cases of DIC in 151 678
      deliveries (3 per 10,000) over the 30 years. Antecedent causes included placental
      abruption (37%), postpartum hemorrhage or hypovolemia (29%), preeclampsia/HELLP
      (14%), acute fatty liver (8%), sepsis (6%), and amniotic fluid embolism (6%). The
      associated maternal morbidity included transfusion >= 5 units (59%), hysterectomy
      (18%), ICU admission (41%), and ATN requiring dialysis (6%). There were three
      maternal deaths, giving a case fatality rate of 1 in 16. The perinatal outcomes
      included stillbirth (25%), neonatal death (5%), and NICU admission (72.5%).
      CONCLUSION: Obstetrical DIC is an uncommon condition associated with high
      maternal and perinatal morbidity and mortality. Prompt recognition and treatment
      with timely administration of blood products is crucial in the management of this
      life-threatening disorder.

PMID- 22472334
TI  - Serious preeclampsia among different immigrant groups.
AB  - OBJECTIVE: Research conducted outside Canada suggests that preeclampsia (PET) may
      be more common among certain ethnic groups. A limitation to prior studies is that
      they did not distinguish between immigrant and non-immigrant women; they also
      included women with mild PET arising near term, the clinical importance of which
      is debatable. We created the term "serious PET" to describe a diagnosis of severe
      PET, eclampsia, or any degree of PET with concomitant preterm delivery, fetal
      death, or maternal hospitalization of seven days or more, and evaluated its risk
      in association with world region of origin among recent immigrants to Ontario.
      METHODS: Using the federal Landed Immigrant Data System database (LIDS), we
      completed a population-based study of 118 849 women who immigrated to Ontario
      between 1985 and 2000. The LIDS was linked to the Canadian Institute for Health
      Information's Discharge Abstracts Database, thereby capturing all
      hospitalizations with subsequent delivery in Ontario between April 1, 2002, and
      March 31, 2009. Rates for serious PET were determined according to maternal world
      region of birth, and odds ratios were adjusted for maternal age, number of live
      births, multifetal pregnancy, diabetes mellitus status, level of formal
      education, place of residence, neighbourhood income quintile, duration of
      residence in Canada, and fiscal year of delivery. RESULTS: Immigrant women from
      the Caribbean (6.8 per 1000; OR 3.34; 95% CI 2.25 to 4.96), Sub-Saharan Africa
      (6.8 per 1000; OR 3.14; 95% CI 2.04 to 4.83) and Hispanic America (5.9 per 1000;
      OR 3.11; 95% CI 1.97 to 4.88) were at highest risk of serious PET relative to
      immigrant women from industrialized nations. The ORs were either unchanged or
      higher when restricted to women without a prior live birth. CONCLUSION: We
      identified immigrant groups at higher risk of serious PET, whose consequences
      would presumably include greater financial costs for hospital care and a negative
      impact on maternal and newborn well-being.

PMID- 22472335
TI  - Robotically assisted laparoscopic myomectomy: a Canadian experience.
AB  - OBJECTIVE: To compare operative and immediate postoperative outcomes of
      robotically assisted laparoscopic myomectomy (RALM) and open myomectomy. METHODS:
      We conducted a retrospective review of 38 cases of RALM performed in women of
      reproductive age with symptomatic uterine fibroids between October 2008 and
      February 2011. Twenty-one cases of open myomectomy were used as historical
      controls. Operative and immediate postoperative outcomes were compared. Data
      analysis was performed using Student t test, chi-square test, and analysis of
      covariance where appropriate. RESULTS: The two groups were comparable in age,
      body mass index, parity, and symptoms. Up to 12 fibroids were resected
      robotically with a mean diameter of 9.1 +/- 2.0 cm and a mean weight of 389 +/-
      170 g (range 73 to 900 g). RALM was associated with less blood loss (decrease in
      hemoglobin concentration 25.6 +/- 12.0g/L) than open myomectomy (37.7 +/- 20.1
      g/L) (P = 0.018). Adjusting for baseline levels, postoperative hemoglobin levels
      were 99 g/L and 88 g/L in the robotic and open groups, respectively (P = 0.005).
      RALM was associated with shorter hospitalization (1.2 +/- 0.5 vs. 2.5 +/- 0.6
      days, P < 0.001) and longer operating times (189.7 +/- 71.5 vs. 92.5 +/- 33.0
      minutes, P < 0.001). Three patients in the open myomectomy group and one in the
      robotic group required blood transfusion. One patient in the robotic group
      developed lumbar plexopathy postoperatively. CONCLUSION: Robotically assisted
      laparoscopic myomectomy is associated with less blood loss and shorter hospital
      stay than myomectomy by laparotomy. Accumulating evidence of the risks and
      benefits of RALM will contribute to enhancing access to this technology on the
      part of women and their surgeons.

PMID- 22472336
TI  - Multidose methotrexate treatment of cervical pregnancy.
AB  - BACKGROUND: Cervical pregnancy is a rare form of ectopic pregnancy. The treatment
      ranges from medical treatment with methotrexate to hysterectomy. CASES: We report
      two cases of cervical pregnancy with fetal cardiac activity that were
      successfully treated with multidose methotrexate. CONCLUSION: Due to the possible
      severe complications of cervical pregnancy and its surgical management, multidose
      methotrexate treatment in hemodynamically stable women is an appropriate option.

PMID- 22472337
TI  - Laparoscopically assisted vaginal hysterectomy in a patient with micro-invasive
      cervical cancer after two liver transplantations.
AB  - BACKGROUND: Advances in surgical techniques and immunosuppressive therapy have
      improved graft survival in transplant recipients. However, intense long-term
      immunosuppression increases the incidence of cancer in these patients compared
      with the general population, not least because of viral infections. Cervical
      cancer is the third most common malignancy worldwide. In early invasive cervical
      cancer, surgery is the treatment of choice. CASE: In 2010, we performed a
      laparoscopically assisted vaginal hysterectomy (LAVH) in a 42-year-old patient
      with micro-invasive cervical adenocarcinoma (FIGO stage IA1) who had undergone
      two liver transplantations in 2006 and 2008. The patient was followed up for 18
      months after surgery. Despite upper abdominal adhesions and minor difficulties in
      inserting the Veress needle, the pneumoperitoneum was created safely. The
      procedure was completed within 157 minutes without any intraoperative
      complications. Blood loss was less than 100 mL. Postoperative course was
      uncomplicated with minimal fluctuations in liver function markers.
      Immunosuppressive therapy was continued without modification. The patient was
      discharged on postoperative day 9. No complications or recurrence were reported
      during the 18-month follow-up. CONCLUSIONS: The laparoscopic approach is a
      justifiable form of surgical management in the treatment of a liver transplant
      recipient with early-stage cervical cancer.

PMID- 22472338
TI  - Assessing residents' disclosure of adverse events: traditional objective
      structured clinical examinations versus mixed reality.
AB  - OBJECTIVE: The skill of disclosing adverse events is difficult to assess.
      Assessment of this competency in medical trainees is commonly achieved via the
      objective structured clinical examination (OSCE) using a standardized patient
      (SP). We hypothesized that the addition of a simulated clinical adverse event
      prior to the SP encounter could increase trainees' engagement and empathy,
      thereby improving performance. The objective of this study was to explore whether
      experiencing a simulated adverse event prior to an SP encounter alters resident
      performance on a disclosure OSCE. METHODS: Sixteen obstetrics and gynaecology
      residents participated in this mixed methods study. Prior to disclosing the
      complication in an SP encounter, residents were randomized either to receive a
      written description of an adverse event, or to experience a mannequin simulation
      of an adverse event. Mean OSCE scores from blinded examiners were compared in
      each group. Focus group discussions elicited residents' reflections on the
      experience of disclosing the adverse event. RESULTS: The mean score was 16.6/23
      +/- 2.9 (range 10 to 20) for the traditional OSCE group and 16.9/23 +/- 1.7
      (range 15 to 20) for the simulation group. Analysis of the focus group data
      revealed several themes, such as the type of context the residents desired, the
      emotional involvement they felt, and their insights about their experience of the
      simulation scenario or with the SP. CONCLUSION: The assessment of adverse event
      disclosure was not enhanced by the addition of a simulated experience. Study
      participants reported that the simulation did not provide the contextual
      information required to elicit empathy and a sense of being emotionally invested
      in the adverse event.

PMID- 22472339
TI  - Dosage requirements for periconceptional folic acid supplementation: accounting
      for BMI and lean body weight.
AB  - OBJECTIVE: To determine folic acid dosage requirements for individuals across a
      broad range of BMI values, using dose per kilogram lean body weight (LBW) as a
      primary predictor of systemic exposure. Steady-state folate concentrations of >=
      15.9 nmol/L were assumed to be sufficient for reducing the risk for neural tube
      defects in the general population. METHODS: Data from a recent study of single
      dose folic acid pharmacokinetics among 12 obese and 12 non-obese women of
      childbearing age were analyzed to determine expected steady-state concentrations.
      The mean folic acid dose per kilogram LBW that achieved serum folate
      concentrations of >= 15.9 nmol/L was applied to a broad range of BMI values to
      evaluate daily dose requirements. RESULTS: Modest differences in folic acid
      requirements were noted for individuals among the non-obese, overweight, and
      obese categories. The current supplementation guidelines suggesting a daily dose
      of 0.4 mg appear to satisfy the needs of women at even the upper extremes of
      obesity. However, because even with appropriate folate supplementation obese
      women have an increased risk of neural tube defects, and they may benefit from
      higher intake and higher serum concentrations of folic acid. CONCLUSION: Current
      guidelines recommend an adequate folic acid dose for obese women of childbearing
      age. Thus, it is unlikely that folate deficiency is associated with the elevated
      risk for neural tube defects in this population.

PMID- 22472340
TI  - The PIERS experience: research or quality improvement?

PMID- 22472341
TI  - Antibiotic prophylaxis in gynaecologic procedures.
AB  - OBJECTIVE: To review the evidence and provide recommendations on antibiotic
      prophylaxis for gynaecologic procedures. OUTCOMES: Outcomes evaluated include
      need and effectiveness of antibiotics to prevent infections in gynaecologic
      procedures. EVIDENCE: Medline and The Cochrane Library were searched for articles
      published between January 1978 and January 2011 on the topic of antibiotic
      prophylaxis in gynaecologic procedures. Results were restricted to systematic
      reviews, randomized control trials/controlled clinical trials, and observational
      studies. Searches were updated on a regular basis and incorporated in the
      guideline to June 2011. Grey (unpublished) literature was identified through
      searching the websites of health technology assessment and health technology
      assessment-related agencies, clinical practice guideline collections, clinical
      trial registries, and national and international medical specialty societies.
      VALUES: The quality of evidence obtained was rated using the criteria described
      in the Report of the Canadian Task Force on Preventative Health Care (Table 1).
      BENEFITS, HARMS, AND COSTS: Guideline implementation should result in a reduction
      of cost and related harm of administering antibiotics when not required and a
      reduction of infection and related morbidities when antibiotics have demonstrated
      a proven benefit. RECOMMENDATIONS: (1) All women undergoing an abdominal or
      vaginal hysterectomy should receive antibiotic prophylaxis. (I-A) (2) All women
      undergoing laparoscopic hysterectomy or laparoscopically assisted vaginal
      hysterectomy should receive prophylactic antibiotics. (III-B) (3) The choice of
      antibiotic for hysterectomy should be a single dose of a first-generation
      cephalosporin. If patients are allergic to cephalosporin, then clindamycin,
      erythromycin, or metronidazole should be used. (I-A) (4) Prophylactic antibiotics
      should be administered 15 to 60 minutes prior to skin incision. No additional
      doses are recommended. (I-A) (5) If an open abdominal procedure is lengthy (e.g.,
      > 3 hours), or if the estimated blood loss is > 1500 mL, an additional dose of
      the prophylactic antibiotic may be given 3 to 4 hours after the initial dose.
      (III-C) (6) Antibiotic prophylaxis is not recommended for laparoscopic procedures
      that involve no direct access from the abdominal cavity to the uterine cavity or
      vagina. (l-E) (7) All women undergoing surgery for pelvic organ prolapse and/or
      stress urinary incontinence should receive a single dose of first-generation
      cephalosporin. (III-B) (8) Antibiotic prophylaxis is not recommended for
      hysteroscopic surgery. (II-2D) (9) All women undergoing an induced (therapeutic)
      surgical abortion should receive prophylactic antibiotics to reduce the risk of
      post-abortal infection. (I-A) (10) Prophylactic antibiotics are not suggested to
      reduce infectious morbidity following surgery for a missed or incomplete
      abortion. (I-E) (11) Antibiotic prophylaxis is not recommended for insertion of
      an intrauterine device. (I-E) However, health care professionals could consider
      screening for sexually transmitted infections in high-risk populations. (III-C)
      (12) There is insufficient evidence to support the use of antibiotic prophylaxis
      for an endometrial biopsy. (III-L) (13) The best method to prevent infection
      after hysterosalpingography is unknown. Women with dilated tubes found at the
      time of hysterosalpingography are at highest risk, and prophylactic antibiotics
      (e.g., doxycycline) should be given. (II-3B) (14) Antibiotic prophylaxis is not
      recommended for urodynamic studies in women at low risk, unless the incidence of
      urinary tract infection post-urodynamics is > 10%. (1-E) (15) In patients with
      morbid obesity (BMI > 35 kg/m2), doubling the antibiotic dose may be considered.
      (III-B) (16) Administration of antibiotics solely to prevent endocarditis is not
      recommended for patients who undergo a genitourinary procedure. (III-E).

PMID- 22472342
TI  - An integrative analysis of transcriptome and proteome provides new insights into
      carotenoid biosynthesis and regulation in sweet orange fruits.
AB  - An integrative analysis of transcriptome and proteome was performed to identify
      differential genes/proteins of a red-flesh sweet orange Cara Cara in comparison
      with a common cultivar Newhall at ripening stages. At the transcript level, gene
      expression was measured with Massively Parallel Signature Sequencing (MPSS), and
      629 genes of these two sweet orange cultivars differed by two fold or more
      (FDR<0.001). At the protein level, a combination of 2DE and MALDI-TOF-TOF MS
      identified 48 protein spots differed in relative abundance (P<0.05). The data
      obtained from comparing transcriptome with proteome showed a poor correlation,
      suggesting the necessity to integrate both transcriptomic and proteomic
      approaches in order to get a comprehensive molecular characterization. Function
      analysis of the differential genes/proteins revealed that a set of candidates was
      associated with carotenoid biosynthesis and the regulation. Overall, some
      intriguing genes/proteins were previously unrecognized related with the formation
      of red-flesh trait, which provided new insights into molecular processes
      regulating lycopene accumulation in a red-flesh sweet orange. In addition, some
      genes/proteins were found to be different in expression patterns between the Cara
      Cara and another red-flesh sweet orange Hong Anliu, and their potential roles
      were further discussed in the present study.

PMID- 22472343
TI  - Endolymphatic sac tumor: case report and review of the literature.
AB  - Endolymphatic sac tumor (ELST) is a rare neoplasm which can be encountered
      sporadically or in Von Hippel-Lindau (VHL) disease. Here we report a sporadic
      case of ELST in 31-year-old man. Neither the symptoms nor a family history of VHL
      disease were found in the patient. CT imaging demonstrated an expansile lytic
      lesion of the mastoid process of the left petrous bone. MR scanning revealed a
      5.2 cm * 4.7 cm * 4.2 cm mass which showed hyperintensity on T1- and T2-weighted
      images. Histologic sections showed a papillary, cystic or glandular architecture.
      The papillary and glandular structures were lined by a single layer of flattened
      cuboidal-to-columnar cells. The stroma of the papillary fronds was richly
      vascularized and chronically inflamed. The tumor showed diffusely positive
      reactivity with cytokeratin (Pan), cytokeratin 19, cytokeratin 5/6, cytokeratin
      7, EMA, vimentin, CD56, and NSE and also showed variable reactivity with glial
      fibrillary acidic protein (GFAP) and VEGF. The Ki-67 immunostain showed a
      proliferation index of < 1%. Because the mass was large, it was difficult to
      extirpate surgically. After surgery, the patient underwent gamma-knife
      radiosurgery for residual tumor. The findings indicate that ELST is a rare
      neoplasm with benign histopathological appearance and clinically destructive
      behavior. Because of the rarity of this tumor, it can easily be confused with
      other tumors such as paraganglioma, middle ear adenoma, adenocarcinoma, papillary
      carcinoma of thyroid or choroid plexus papilloma. Owing to its locally aggressive
      nature, it is difficult to extirpate surgically when it is large. VIRTUAL SLIDES:
      The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7973320646763012.

PMID- 22472344
TI  - Effectiveness of leg movement in reducing leg swelling and discomfort in lower
      extremities.
AB  - Various occupations required that workers stand for long periods, causing
      discomfort and pain. This study considered the effectiveness of three leg
      movements in relieving discomfort of the lower extremities during long periods of
      standing at work. Ten paid male subjects with no history of problems of the lower
      extremities were enrolled in this study. They performed three leg movements on a
      hard floor while standing for 4 h in a laboratory setting. Each 1 h experimental
      test had two phases - 50 min of standing, followed by 10 min of rest. During the
      period of standing, one the following leg movements was made. No movement (no
      change in posture), ankle movement (twice, for 2 min each time), and hip movement
      (twice, for 2 min each time). Observations revealed that the three leg movements
      yielded different degrees of lower limb swelling. The percentage changes in thigh
      (1.22%) and shank (1.32%) circumferences were largest during prolonged standing
      without any movement and lowest during prolonged standing with ankle movement
      (0.61%) and hip movement (0.80%). The relationship between perceived discomfort
      and standing time was determined. The subjects perceived the most shank
      discomfort (5.8) during the 4 h test without any movement. Leg movement greatly
      influenced perceived discomfort of the shank. The results of this study suggested
      that workers should move their ankles and hips for a short period following
      prolonged standing for 30 min to reduce lower extremity discomfort.

PMID- 22472345
TI  - Cell division control by the Chromosomal Passenger Complex.
AB  - The Chromosomal Passenger Complex (CPC) consisting of Aurora B kinase, INCENP,
      Survivin and Borealin, is essential for genomic stability by controlling multiple
      processes during both nuclear and cytoplasmic division. In mitosis it ensures
      accurate segregation of the duplicated chromosomes by regulating the mitotic
      checkpoint, destabilizing incorrectly attached spindle microtubules and by
      promoting the axial shortening of chromosomal arms in anaphase. During
      cytokinesis the CPC most likely prevents chromosome damage by imposing an
      abscission delay when a chromosome bridge connects the two daughter cells.
      Moreover, by controlling proper cytoplasmic division, the CPC averts
      tetraploidization. This review describes recent insights on how the CPC is
      capable of conducting its various functions in the dividing cell to ensure
      chromosomal stability.

PMID- 22472346
TI  - Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling
      pathway in cultured podocytes.
AB  - The glomerular capillary wall, composed of endothelial cells, the glomerular
      basement membrane and the podocytes, is continually subjected to hemodynamic
      force arising from tractional stress due to blood pressure and shear stress due
      to blood flow. Exposure of glomeruli to abnormal hemodynamic force such as
      hyperfiltration is associated with glomerular injury and progressive renal
      disease, and the conversion of mechanical stimuli to chemical signals in the
      regulation of the process is poorly understood in podocytes. By examining DNA
      fragmentation, apoptotic nuclear changes and cytochrome c release, we found that
      shear stress induced cell apoptosis in cultured podocytes. Meanwhile, podocytes
      exposed to shear stress also stimulated c-Src phosphorylation, phospholipase D
      (PLD) activation and mammalian target of rapamycin (mTOR) signaling. Using the
      antibodies against c-Src, PLD(1), and PLD(2) to perform reciprocal co
      immunoprecipitations and in vitro PLD activity assay, our data indicated that c
      Src interacted with and activated PLD(1) but not PLD(2). The inhibition of shear
      stress-induced c-Src phosphorylation by PP(2) (a specific inhibitor of c-Src
      kinase) resulted in reduced PLD activity. Phosphatidic acid, produced by shear
      stress-induced PLD activation, stimulated mTOR signaling, and caused podocyte
      hypertrophy and apoptosis.

PMID- 22472347
TI  - Cohesin in determining chromosome architecture.
AB  - Cells use ring-like structured protein complexes for various tasks in DNA
      dynamics. The tripartite cohesin ring is particularly suited to determine
      chromosome architecture, for it is large and dynamic, may acquire different
      forms, and is involved in several distinct nuclear processes. This review focuses
      on cohesin's role in structuring chromosomes during mitotic and meiotic cell
      divisions and during interphase.

PMID- 22472348
TI  - The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer;
      possible mechanism through inhibiting VEGF and hypoxia inducible factor-1alpha
      targeted gene expression.
AB  - Tumor hypoxia has been considered to be a potential therapeutic target, because
      hypoxia is a common feature of solid tumors and is associated with their
      malignant phenotype. In the present study, we investigated the antitumor effect
      of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2
      quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of
      hypoxia inducible factor-1alpha (HIF-1alpha), and consequently vascular
      endothelial cell growth factor (VEGF) expression in pancreatic cancer. The
      antitumor effects of TX-2098 under hypoxia were tested against various human
      pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic
      cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice
      bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were
      treated with TX-2098. Tumor volume, survival and expression of HIF-1 and
      associated molecules were evaluated in treatment versus control groups. In vitro,
      TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In
      s.c model, tumors from nude mice injected with pancreatic cancer cells and
      treated with TX-2098 showed significant reductions in volume (P<0.01 versus
      control). Quantitative real-time reverse transcription-PCR analysis revealed that
      TX-2098 significantly inhibited mRNA expression of the HIF-1 associated
      molecules, VEGF, glucose transporter 1 and Aldolase A (P<0.01 versus control).
      These treatments also prolong the survival in orthotopic models. These results
      suggest that the effect of TX-2098 in pancreatic cancer might be correlated with
      the expression of VEGF and HIF-1 targeted molecules.

PMID- 22472350
TI  - A systematic review of growth hormone for hip fractures.
AB  - OBJECTIVE: To evaluate the clinical effectiveness of growth hormone (GH) for hip
      fractures. DESIGN: Based on the principles and methods of Cochrane systematic
      reviews, we searched the Cochrane Library (2011, 3 issue), PubMed (1966 to
      October 2011), EMBASE (1974 to October 2011), OVID database (1963 to October
      2011), Chinese Bio-medicine database (1978 to October 2011), China Journal Full
      text Database (1979 to October 2011), and VIP database (1989 to October 2011).
      Randomized controlled trials (RCTs) of GH treatment for hip fractures were
      included. We assessed the quality of included trials according to the Cochrane
      Handbook for Systematic Reviews of Interventions Version. The Cochrane
      Collaboration's software RevMan 5.0 was used for meta-analysis. RESULTS: 3 RCTs
      with a total of 162 hip fractures patients were included. Results of GH compared
      to placebo treatment showed that IGF-I levels significantly increased in the
      short term, but no significant differences in the long term. Additionally, there
      was no statistical difference in adverse events. Only one trial reported the
      measurement of bone mineral content (BMC), which showed that GH group was
      unchanged while the placebo group lost BMC at both 4 weeks and 8 weeks. Only one
      study measuring BMC showed no significant differences in the change of the MBI
      scores between GH group and placebo group; however, the changes from baseline in
      the hGH group were less than that in the placebo group among the older than 75
      years group. Owing to the difference of measurement indexes in those studies, we
      could not perform a meta-analysis. CONCLUSIONS: With the low quality of current
      evidence, GH may be effective in hip fractures. More carefully designed, double
      blinded and placebo-controlled randomized trials with large numbers of
      participants about GH in the treatment of hip fractures are required.

PMID- 22472349
TI  - Chemokine CXCL12 activates dual CXCR4 and CXCR7-mediated signaling pathways in
      pancreatic cancer cells.
AB  - BACKGROUND: Previously assumed to be a select ligand for chemokine receptor
      CXCR4, chemokine CXCL12 is now known to activate both CXCR4 and CXCR7. However,
      very little is known about the co-expression of these receptors in cancer cells.
      METHODS: We used immunohistochemistry to determine the extent of co-expression in
      pancreatic cancer tissue samples and immunoblotting to verify expression in
      pancreatic cancer cell lines. In cell culture studies, siRNA was used to knock
      down expression of CXCR4, CXCR7, K-Ras and beta-arrestin -2 prior to stimulating
      the cells with CXCL12. Activation of the mitogen-activated protein kinase pathway
      (MAPK) was assessed using both a Raf-pull down assay and western blotting. The
      involvement of the receptors in CXCL12-mediated increases in cell proliferation
      was examined via an ATP-based proliferation assay. RESULTS: First, we discovered
      frequent CXCR4/CXCR7 co-expression in human pancreatic cancer tissues and cell
      lines. Next, we observed consistent increases in ERK1/2 phosphorylation after
      exposure to CXCL12 or CXCL11, a CXCR7 agonist, in pancreatic cancer cell lines co
      expressing CXCR4/CXCR7. To better characterize the receptor-mediated pathway(s),
      we knocked down CXCR4 or CXCR7, exposed the cells to CXCL12 and examined
      subsequent effects on ERK1/2. We observed that CXCR7 mediates the CXCL12-driven
      increase in ERK1/2 phosphorylation. Knockdown of CXCR4 expression however,
      decreased levels of K-Ras activity. Conversely, KRAS knockdown greatly reduced
      CXCL12-mediated increases in ERK1/2 phosphorylation. We then evaluated the role
      of beta-arrestin-2, a protein directly recruited by chemokine receptors. We
      observed that beta-arrestin-2 knockdown also inhibited increases in ERK1/2
      phosphorylation mediated by both CXCR4 and CXCR7. Finally, we investigated the
      mechanism for CXCL12-enhanced cell proliferation and found that either receptor
      can modulate cell proliferation. CONCLUSIONS: In summary, our data demonstrate
      that CXCR4 and CXCR7 are frequently co-expressed in human pancreatic cancer
      tissues and cell lines. We show that beta-arrestin-2 and K-Ras dependent pathways
      coordinate the transduction of CXCL12 signals. Our results suggest that the
      development of therapies based on inhibiting CXCL12 signaling to halt the growth
      of pancreatic cancer should be focused at the ligand level in order to account
      for the contributions of both receptors to this signaling pathway.

PMID- 22472351
TI  - Brentuximab associated progressive multifocal leukoencephalopathy.

PMID- 22472352
TI  - Ventriculoperitoneal shunt surgery and the incidence of shunt revision in adult
      patients with hemorrhage-related hydrocephalus.
AB  - OBJECTIVE: Ventriculoperitoneal shunt surgery remains the most widely accepted
      neurosurgical procedure for the management of hydrocephalus. However, shunt
      failure and complications are common and may require multiple surgical procedures
      during a patient's lifetime. The purpose of this study is to evaluate the
      ventriculoperitoneal shunt surgery and the incidence of shunt revision in adult
      patients with hemorrhage-related hydrocephalus. METHODS: Adult patients who
      underwent ventriculoperitoneal shunt placement for hemorrhage-related
      hydrocephalus from October 1990 to October 2009 were included in this study.
      Medical charts, operative reports, imaging studies, and clinical follow-up
      evaluations were reviewed and analyzed retrospectively. RESULTS: A total of 133
      adult patients with the median age of 54.5 years were included. Among patients,
      41% were males, and 62% Caucasians. The overall shunt revision rate was 51.9%.
      The shunt revision rate within the first 6 months after the initial placement of
      ventriculoperitoneal shunts was 45.1%. The median time to first shunt revision
      was 0.50 (95% CI, 0.24-9.2) months. No significant association was observed
      between perioperative variables (gender, ethnicity, hydrocephalus type, or
      hemorrhage type) and the shunt revision rate in these patients. Major causes of
      shunt revision include infection (3.6%), overdrainage (7.6%), obstruction (4.8%),
      proximal shunt complication (7.6%), distal shunt complication (3.6%), old shunt
      dysfunction (6.8%), valve malfunction (10.0%), externalization (3.6%), shunt
      complication (12.0%), shunt adjustment/replacement (24.0%) and other (16.4%).
      CONCLUSION: Although ventriculoperitoneal shunting remains to be the treatment of
      choice for adult patients with post hemorrhage-related hydrocephalus, a thorough
      understanding of predisposing factors related to the shunt failure is necessary
      to improve treatment outcomes.

PMID- 22472353
TI  - Terson haemorrhage in patients suffering aneurysmal subarachnoid haemorrhage: a
      prospective analysis of 60 consecutive patients.
AB  - OBJECTIVE: The concomitance of vitreous/subhyaloid haemorrhage (Terson syndrome;
      TS) and aneurysmal subarachnoid haemorrhage (aSAH) is commonly underestimated.
      The aim of this study was to determine the incidence of TS and to identify
      parameters that predispose its development, indicate the severity of the
      underlying disease, and predict outcome. METHODS: Sixty consecutive patients
      suffering from aSAH were included in this study. The admitting Glasgow Coma Scale
      scores (GCS), Hunt & Hess (H&H) and Fisher grades were documented. All
      participants were ophthalmologically examined. The outcome at discharge was
      estimated using the Glasgow Outcome Scale (GOS). RESULTS: Of the 60 patients
      admitted for aSAH, eleven (18.3%) displayed TS within 24h after aneurysm rupture.
      Statistical analysis revealed a significant relation between TS and either high
      Fisher- (3.0 vs. 2.32; p=0.008) or H&H- (4.09 vs. 2.69; p=0.001) and low GCS-
      (5.55 vs. 12.87; p<0.001) scores. Compared with the non-TS group, patients with
      TS displayed generally worse outcomes (mean GOS 2.09 vs. 3.53; p=0.007),
      including a significantly higher mortality (36.4 vs. 10.2%; p=0.028). CONCLUSION:
      Terson syndrome is likely to occur in severe aSAH with poor admission scores and
      indicates a worse functional outcome. An ophthalmological examination is strongly
      recommended in aSAH patients with poor admission scores.

PMID- 22472354
TI  - Management of EGFR-inhibitor associated rash: a retrospective study in 49
      patients.
AB  - BACKGROUND: In recent years inhibitors directed against the epidermal growth
      factor receptor (EGFR) have evolved as effective targeting cancer drugs.
      Characteristic papulopustular exanthemas, often described as acneiform rashes,
      are the most frequent adverse effect associated with this class of novel cancer
      drugs and develop in > 90% of patients. Notably, the rash may significantly
      compromise the patients' quality of life, thereby potentially leading to
      incompliance as well as dose reduction or even termination of the anti-EGFR
      therapy. Yet, an effective dermatologic management of cutaneous adverse effects
      can be achieved. Whereas various case reports, case series or expert opinions on
      the management of EGFR-inhibitor (EGFRI) induced rashes have been published, data
      on systematic management studies are sparse. METHODS: Here, we present a
      retrospective, uncontrolled, comparative study in 49 patients on three
      established regimens for the management of EGFRI-associated rashes. RESULTS:
      Strikingly, patients' rash severity improved significantly over three weeks of
      treatment with topical mometason furoate cream, topical prednicarbate cream plus
      nadifloxacin cream, as well as topical prednicarbate cream plus nadifloxacin
      cream plus systemic isotretinoin. CONCLUSIONS: In summary our results demonstrate
      that EGFRI-associated rashes can be effectively managed by specific dermatologic
      interventions. Whereas mild to moderate rashes should be treated with basic
      measures in combination with topical glucocorticosteroids or combined regiments
      using glucocorticosteroids and antiseptics/antibiotics, more severe or therapy
      resistant rashes are likely to respond with the addition of systemic retinoids.

PMID- 22472355
TI  - Hyaluronan-supplemented buffers preserve adhesion mechanisms facilitating
      cryopreservation of human hepatic stem/progenitor cells.
AB  - The supply of human hepatic stem cells (hHpSCs) and other hepatic progenitors has
      been constrained by the limited availability of liver tissues from surgical
      resections, the rejected organs from organ donation programs, and the need to use
      cells immediately. To facilitate accessibility  to these precious tissue
      resources, we have established an effective method for serum-free
      cryopreservation of the cells, allowing them to be stockpiled and stored for use
      as an off-the-shelf product for experimental or clinical programs. The method
      involves use of buffers, some serum-free,  designed for cryopreservation and
      further supplemented with hyaluronans (HA) that preserve adhesion mechanisms
      facilitating postthaw culturing of the cells and preservation of functions.
      Multiple cryopreservation buffers were found to yield high viabilities (80-90%)
      of cells on thawing  of the progenitor cells. Serum-free CS10 supplemented with
      0.05% hyaluronan proved the most effective, both in terms of viabilities of cells
      on thawing and in yielding cell attachment and formation of expanding colonies of
      cells that stably maintain the stem/progenitor cell phenotype. Buffers  to which
      0.05 or 0.1% HAs were added showed cells postthaw to be phenotypically stable as
      stem/progenitors, as well as having a high efficiency of attachment and expansion
      in culture. Success correlated with improved expression of adhesion molecules,
      particularly CD44, the hyaluronan receptor,  E-cadherin, beta4 integrin in
      hHpSCs, and beta1 integrins in hepatoblasts. The improved methods in
      cryopreservation offer more efficient strategies for stem cell banking in both
      research and potential therapy applications.

PMID- 22472356
TI  - Genetic modification of human adipose-derived stem cells for promoting wound
      healing.
AB  - BACKGROUND: Diverse growth factors secreted from human adipocyte-derived stem
      cells (hASCs) that support or manage adjacent cells have been studied for
      therapeutic potentials to a variety of pathological models. However, senescent
      growth arrest in hASCs during in vitro culture and subsequent defective
      differentiation potential, have been technical barriers to further genetic
      modification of hASCs for functional improvement. OBJECTIVE: We investigated the
      feasibility of long-term hASC culture to enhance their therapeutic use. METHODS:
      We used a MYC variant to generate hASCs expressing v-myc and determined their
      growth potential and growth factor secretion profile. We further introduced an
      AKT variant to generate constitutively active (CA)-Akt/v-myc hASCs. Finally, we
      tested the ability of promoting wound healing of medium conditioned with CA-Akt/v
      myc hASCs. RESULTS: The v-myc hASCs actively proliferated longer than control
      hASCs. Increased secretion of vascular endothelial growth factor (VEGF) by v-myc
      hASCs promoted the migration potential of hASCs and vasculogenesis in co-cultured
      endothelial cells. Additional genetic modification of v-myc hASCs using CA-Akt
      further increased VEGF secretion. In addition, injection of CA-Akt/v-myc hASCs-CM
      into wound-mice model promoted wound healing compared to normal hASCs-CM.
      CONCLUSION: Genetic modification of hASCs to stimulate secretion of growth
      factors is a novel strategy to maximize their paracrine effect and improve their
      therapeutic potential.

PMID- 22472357
TI  - [AL amyloidosis].
AB  - AL amyloidosis is a systemic disease characterised by pathogenetic proteins
      produced by malignant plasma cells and the deposition of them in different organs
      of the body. Amyloidogenic protein is the light chain of the monoclonal
      immunoglobulin, which becomes water insoluble, precipitates and deposites in the
      extracellular space resulting damage of organ function. AL amyloidosis belongs to
      plasma cell dyscrasias or it can associate to other monoclonal B-cell diseases.
      Diagnosis - such as in case of other types of amyloidosis - is based on
      histology. Identification of the amyloidogenic protein often needs special
      examinations. The goal of the therapy is the eradication of the malignant cell
      clone. Therapeutical armamentarium has been largely flared in the past few
      decades, several drugs with new mechanisms of action are available (thalidomide,
      lenalidomide, bortezomib). The standard treatment is high dose chemotherapy
      followed by autologous stem cell transplantation in case of eligible patients.
      Transplantation uneligible patients can be treated with a low dose alkylating
      agent with or without dexamethasone, or with the new agents. The therapeutical
      decision must be preceded by very thorough risk assessment. Early diagnosis and
      the prompt beginning of the treatment has great significance because the evolving
      functional abnormalities of parenchymal organs (mainly cardiac failure) prevents
      the effectivity of the treatment. Amyloidosis is an orphan disease, special
      centers play a significant role in the field of clinical trials.

PMID- 22472358
TI  - [The role of methylglyoxal metabolism in type-2 diabetes and its complications].
AB  - Transient or chronic hyperglycaemia increases the formation of intracellular
      reactive oxygen species and aldehydes. The accumulation of reactive aldehydes is
      implicated in the development of diabetic complications. Methylglyoxal, a glucose
      dependent alpha-dicarbonyl might be the most important reactive aldehyde in
      diabetes and its complications. Diabetes was the first disease in which evidence
      emerged for the increased formation of methylglyoxal in the cells and in the
      serum. Methylglyoxal has a toxic effect on insulin secretion from pancreatic beta
      cells, and on modifications of proteins and nucleic acids. Moreover,
      methylglyoxal is one of the major precursors of advanced glycation end-products.
      The glyoxalase enzyme system that exists in all mammalian cells is catalyzing the
      detoxification of methylglyoxal. This review summarizes the methylglyoxal
      metabolism in normoglycaemic and hyperglycamic conditions and the role of
      methylglyoxal in the development of late diabetic microvascular complications.

PMID- 22472359
TI  - [Allopurinol-induced hypersensitivity syndrome].
AB  - Allopurinol is an effective urate lowering drug, which is usually well-tolerated
      with no adverse effects in most cases, but about 2% of the treated patients
      develop a skin rash, and patients may experience severe allopurinol-induced
      hypersensitivity syndrome. AIMS: The aim of the authors was to summarize and
      present the clinical manifestations of allopurinol-induced hypersensitivity in
      patients treated at the Department of Dermatology and Allergology, University of
      Szeged in order to identify potential associations with this syndrome. METHODS:
      Retrospective review of all patients who were referred to the department with
      allopurinol-induced hypersensitivity syndrome in the last four years. RESULTS:
      During four years, 11 patients were treated with allopurinol-induced
      hypersensitivity syndrome. The average age was 70.3 years. Before the initiation
      of allopurinol therapy, 36% of patients had already suffered from various degrees
      of renal impairment, and 72% of them had been taking thiazide diuretics.
      Cutaneous manifestations were mainly generalized, erythematous, maculopapular
      exanthemas (9 patients, 82%), and two patients showed signs of erythema
      multiforme (18%). Asymptomatic hyperuricemia was the indication for allopurinol
      therapy in all patients. CONCLUSIONS: Allopurinol-induced hypersensitivity
      syndrome is a severe, life-threatening disease. Administration of allopurinol
      should be initiated with clear indications in appropriate dose. Old age,
      underlying renal impairment and concomitant thiazide diuretic intake should be
      considered as potential risk factors for developing hypersensitivity syndrome.

PMID- 22472360
TI  - [Psychological factors of successful kidney transplantations. The effects of
      anxiety and intrapsychic integration of the organ on recovery].
AB  - Transplant patients' attitudes and representations related to their illness,
      their body, and the healing process have a significant impact on their recovery.
      AIMS: The study involved 51 patients from the Department of Surgery, University
      of Szeged, Hungary. The primary aim was to examine the possible connections
      between emotional and mood factors, illness and body representations, and the
      successful onset of renal functions after surgery. METHODS: Patients were tested
      with a combination of 4 instruments: Spielberger's anxiety scale and Beck
      depression scale, self and organ drawings, and a questionnaire designed by the
      authors. RESULTS: Our data suggest that high distress correlates with kidney
      disfunction after transplantation. Patients with higher anxiety drew the kidney
      larger in their projective drawing test. It was a remarkable result that post
      transplant blood test on Day 10 showed significantly lower creatinine and urea
      levels in those patients who had drawn the kidney smaller in their projective
      drawing test. This might indicate that the organ's normal intrapsychic
      integration and the related kidney functions are disturbed. CONCLUSIONS: The
      results of this study provide useful information about the psychological
      background, which has received relatively little attention so far. It can also
      give important clues for further research on clinical health psychology in
      supporting the healing process.

PMID- 22472362
TI  - [The establishment of the Marfan syndrome biobank in Hungary - Erratum].

PMID- 22472363
TI  - Single-port cholecystectomy in a patient with situs inversus totalis presenting
      with cholelithiasis: a case report.
AB  - INTRODUCTION: Situs inversus totalis (mirror image organs) is a rare condition
      and may affect the intra-abdominal viscera as well as the intrathoracic organs.
      Cholelithiasis is not more common in these conditions, but the diagnosis may be
      more difficult. CASE PRESENTATION: We present the case of a 59-year-old African
      woman with gallstones and situs inversus totalis. A single-port cholecystectomy
      was performed using a single trocar access device (SITRACC). CONCLUSIONS: The
      procedure was uneventful, showing that this approach may be an option for this
      kind of surgery even in patients with situs inversus totalis.

PMID- 22472364
TI  - Hospital-diagnosed late sequelae after female Chlamydia trachomatis infections in
      1990-2006 in Turku, Finland.
AB  - BACKGROUND: Rather little is known about the late sequelae of previously detected
      female Chlamydia infections. METHODS: The late sequelae of previous female
      Chlamydia infections detected during a 15-year period in a south-western Finnish
      university hospital were surveyed. Hospital records of women with positive
      laboratory diagnoses of Chlamydia trachomatis as a sign of genital infection were
      collected from the years 1990-2006 and subsequently linked to known or suspected
      in-hospital-treated late Chlamydia complications. RESULTS: The annual number of
      late complications has increased in proportion to the increasing trend of
      detected Chlamydia cases. 239 late complications of the total of 4,920 previously
      detected Chlamydia-positive infections were observed. The most frequent in
      hospital-treated complications were disturbances in early pregnancy (n = 72) and
      low abdominal pain (n = 67). The others were 45 genital tract or pelvic
      infections, 34 cases of tubal or unknown infertility and 21 complications of late
      pregnancy and delivery. CONCLUSION: The late sequelae of Chlamydia infections
      need increasing attention in hospitals.

PMID- 22472365
TI  - Congenital cystic adenomatoid malformation of lung in adults: 2 rare cases report
      and review of the literature.
AB  - Congenital cystic adenomatoid malformation (CCAM), also named congenital
      pulmonary airway malformation (CPAM), is a congenital abnormality of lung which
      is uncommon in adults. Here we present 2 adult cases of CCAM with unusual
      clinical and pathologic findings. One case was complicated with aspergillosis
      which was seldom reported. The other case was suffered bilateral lesions and the
      patient's mother had been previously radiographically discovered bilateral cystic
      lesions that CCAM could not be ruled out. A review of currently published related
      literatures has also been provided. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/6406766736634578.

PMID- 22472366
TI  - Endovascular treatment of isolated spontaneous celiac artery dissection.
AB  - This report presents the case of a patient with isolated spontaneous celiac
      artery dissection. The patient developed acute abdominal pain that was induced by
      eating. Computed tomography and selective angiography revealed an intimal flap
      that separated the true and false lumens located 3 cm from the origin of the
      celiac artery. We treated the patient with a stent that was deployed
      endovascularly into the celiac artery to seal the entry site. Postoperative
      angiography revealed that the graft was patent and the follow-up period was
      uneventful. The etiology, clinical features, diagnostic modalities and treatment
      options of isolated spontaneous celiac artery dissection are reported.

PMID- 22472367
TI  - Emergency endovascular treatment of acute symptomatic or ruptured abdominal
      aortic aneurysm: a single-center experience.
AB  - The purpose of this study is to report our early experience with endovascular
      treatment of patients with symptomatic non-ruptured (sAAA) or ruptured (rAAA)
      abdominal aortic aneurysms. Between September 2005 and September 2008, all
      patients with a diagnosis of sAAA or rAAA were evaluated for endovascular
      suitability. We did not consider hemodynamic instability to be a contraindication
      for endovascular aneurysm repair (EVAR). Patients whose aneurysm anatomy was not
      suitable for EVAR received open repair (OR). A total of 46 patients with sAAA or
      rAAA underwent emergency EVAR: in particular, 18/46 patients were treated for
      sAAA and 28/46 for rAAA. Successful stent-graft deployment was achieved in 44
      patients (96%); we had two open surgical conversions. The 30-day mortality rate
      was 19.5%. Nine patients died during the first 30 postoperative days: four
      patients died within 24 hours because of severe hypovolemic shock, two died of
      respiratory failure, one died as a result of bowel ischemia and two because of
      myocardial infarction after hospital discharge. Complete follow-up data were
      available for 35 patients (median 185 days; range 30-730 days). In conclusion,
      endovascular treatment is feasible and the early experience is promising. The
      capability of offering EVAR and OR for sAAA and rAAA according to our experience
      suggests that EVAR and OR should be regarded as complementary techniques to
      improve outcome of patients with acute AAA.

PMID- 22472368
TI  - Daily temperature predicts assault and may allow more efficient policing.

PMID- 22472369
TI  - Unhealed metastatic cutaneous manifestation masquerading as bilateral forearm
      eczema.

PMID- 22472370
TI  - Blastocystis hominis and recurrent megacolon: a causative or fortuitous
      association?

PMID- 22472371
TI  - Hernia formation and persistent fistula after percutaneous endoscopy gastrostomy:
      unusual complications of a common procedure.

PMID- 22472372
TI  - Jejunal diverticulitis: a rare cause of abdominal pain.

PMID- 22472373
TI  - Four extremity necrotizing fasciitis without involvement of the trunk or head.

PMID- 22472374
TI  - Whipple's disease: the great pretender.

PMID- 22472375
TI  - Improvement of the quality of life of a patient with colon ulceration of systemic
      lupus erythematosus by successful surgical treatment: report of a case.

PMID- 22472376
TI  - Primary rectal squamous cell carcinoma.

PMID- 22472377
TI  - Pheochromocytoma and renal artery aneurysm in neurofibromatosis type 1.

PMID- 22472378
TI  - Adrenal cyst: huge retroperitoneal mass associated with a left hypochondralgia in
      a young female.

PMID- 22472379
TI  - Obturator hernia.

PMID- 22472380
TI  - Changing trend in distribution of gastric carcinoids: a first instance of typical
      sporadic gastric cardia carcinoid.

PMID- 22472381
TI  - Remnant large retrosternal thyroid goiter after thyroidectomy.

PMID- 22472382
TI  - Incidental finding of bulky retroperitoneal lymphadenopathy in a patient with a
      primary occult small gastric carcinoid tumor.

PMID- 22472383
TI  - Delayed tracheal rupture after thyroidectomy.

PMID- 22472384
TI  - Increased mortality from delayed diagnosis and treatment of obturator hernia in
      elderly patients.

PMID- 22472385
TI  - Laparoscopic excision of a gastric lymphatic malformation.

PMID- 22472386
TI  - Malignant insulinoma presenting as upper gastrointestinal bleeding.

PMID- 22472387
TI  - Rib hemangioma presenting as an asymptomatic mass.

PMID- 22472388
TI  - Primary primitive neuroectodermal tumor of the small bowel: not just for kids.

PMID- 22472389
TI  - Pilonidal sinus disease of the scalp.

PMID- 22472390
TI  - Nonfunctional retroperitoneal paraganglioma simulating pancreatic tumor: report
      of a case.

PMID- 22472391
TI  - Peritoneal bands: a review of anatomical distribution and clinical implications.
AB  - The complexity of embryological development of the gastrointestinal tract and
      mesentery provides a platform for the formation of a wide variety of variant
      veils, folds, and membranes, collectively termed peritoneal bands. These
      structures, which represent anatomically unabsorbed portions  of the omentum and
      mesentery, although often benign, have the potential to cause clinically
      significant manifestations in both the neonate and adult. Although these deviant
      structures may be identified over a broad range of the abdominal cavity, they are
      most commonly identified in the regions  of the duodenum, duodenojejunal flexure,
      ileocecal junction, and ascending colon. As a result of the diverse location of
      these variant structures, clinical manifestations are highly variable, ranging
      from acute presentations of intestinal necrosis as a result of strangulated
      midgut volvulus  to chronic, vague abdominal pain. This article seeks to
      highlight the importance of a thorough anatomical understanding of the
      distribution of the various abnormal peritoneal folds, bands, and ligaments,
      which may result from aberrations in embryonic gastrointestinal development and
      their  respective clinical implications. Moreover, to advance the knowledge of
      peritoneal bands, this article discusses the appropriate diagnostic studies and
      treatment interventions required for these variant structures.

PMID- 22472392
TI  - Sir William Osler, M.D., C.M.

PMID- 22472393
TI  - Survey on ventral hernias: surgeon indications, contraindications, and management
      of large ventral hernias.
AB  - Repair of ventral hernias constitutes one of the most common surgical procedures.
      Although an abundance of data exists on objective outcome measures, very little
      information exists on subjective measures of surgeon preference and patient
      satisfaction in surgical management of ventral  hernias. Moreover, there are
      minimal data on indications for elective repair of ventral hernias. Two
      questionnaires were sent to a population of general and plastic surgeons active
      in hernia surgery. The first of these aimed at gathering information from
      surgeons about their indications and  contraindications for repair of ventral
      hernias. The second survey was aimed at determining surgeons' perception of
      patient satisfaction with repair of large ventral hernias (greater than 15 cm
      width). Five hundred sixty-eight surgeons responded to the first survey and 336
      responded to the  second survey. The most common indications for elective repair
      of abdominal wall hernias were generalized pain (68.7%) and cosmesis (54.6%),
      whereas the most common contraindications were morbid obesity (43.3%), American
      Society of Anesthesiologists Class III or IV (35.4%), and enterocutaneous 
      fistula (33.1%). The majority of surgeons do not routinely repair large abdominal
      wall hernias in asymptomatic patients, but 31.6 per cent do repair asymptomatic
      large hernias. Most surgeons reported that the majority of patients had
      resolution of pain and subjective impression of improved  cosmesis after surgery.
      This study demonstrates uniform indications and contraindications for surgical
      repair of ventral hernias among surgeons as well as surgeons' perception of
      improvements in satisfaction of most patients after surgery. Future studies will
      focus on comparing surgeon and  patient satisfaction.

PMID- 22472394
TI  - Flail chest injury: are we making any progress?
AB  - Flail chest represents a severe injury with mortality historically reported at up
      to 30 per cent. Although management has changed dramatically over the past
      several decades, there is a paucity of large recent series. With Institutional
      Review Board approval, a retrospective review of  all patients with flail chest
      admitted from January 2001 through May 2010 was undertaken. Patient demographics,
      outcomes, and cause of death were specifically analyzed with univariate and
      multivariate analysis. There were 164 patients at a median age of 51.4 years.
      Head injury and pulmonary  contusion were present in 67 (40.8%) and 125 (77%),
      respectively. Pneumonia developed in 72 (43.9%). There were 41 deaths (25%), for
      which flail chest contributed to 15 (9.1%). Of the patients with flail chest
      related death, the majority (n = 10 [66.7%]) died within 48 hours of
      presentation.  There were only five deaths (3.0%) related to flail chest after 48
      hours. Multivariate analysis of ventilator dependency revealed requirement for
      laparotomy (P = 0.019) or tracheostomy (P < 0.0001) and pneumonia (P = 0.0002) as
      significant. Pneumonia was the most significant  independent predictor of overall
      (P < 0.0001) and intensive care unit length of stay (P < 0.0001). The mortality
      associated with flail chest has greatly improved; however, the rate of pneumonia
      remains high. Further efforts at pneumonia prevention are thus warranted.

PMID- 22472395
TI  - Factors predicting need for and delay in surgery in small bowel obstruction.
AB  - Safe management of small bowel obstruction (SBO) depends on rapid diagnosis. The
      objective of this study was to determine factors predictive for operation and
      resulting in operative delay. A retrospective review was done of 1613 patients
      over 4 years (2003 to 2007) with International  Classification of Diseases, 9th
      Revision codes for SBO. After excluding patients with incomplete clinical data,
      incorrectly coded, and age younger than 5 years, 872 patients were reviewed.
      Analysis was done for factors predictive for operation and factors associated
      with operative delay. Statistics  was done using t test, Wilcoxon-rank-sum, and
      chi(2). Four hundred ninety-four patients (56.6%) underwent surgery for SBO.
      Three hundred seventy-eight patients (43.4%) were managed nonoperatively. Of
      factors examined, younger patients (P = 0.001), no previous operation  (P <
      0.001), and absence of adhesive disease (P < 0.001) were more likely to go to
      operation. Acquiring a computed tomographic scan (P = 0.029) or radiograph (P <
      0.001) were the only factors that increased time to the operating room (OR).
      Increased time  to the OR was associated with a higher incidence of bowel
      resection. With those with time to OR less than 24 hours, 39 of 325 patients(12%)
      had bowel resection versus time to OR greater than 24 hours, 23 of 80 patients
      (29%) required bowel resection. Identifying patients who may safely  undergo
      nonoperative management remains difficult. Delay in operation for SBO places
      patients at higher risk for bowel resection.

PMID- 22472396
TI  - Prevalence of clostridium difficile in excluded colons.
AB  - Clostridium difficile infection is associated with substantial morbidity and
      mortality, increased duration of hospitalization, and a marked economic impact.
      Several case reports and case series have described C. difficile infection in
      excluded bowels or immediately after  reversal of defunctioning ileostomy. The
      aim of this prospective study is to detect whether the excluded colon is
      associated with a higher rate of C. difficile colonization than the normal
      population, which may increase the risk of C. difficile infection. Patients with
      defunctioning  loop ileostomy, undergoing closure of ileostomy to restore bowel
      continuity, were prospectively recruited. Two stool samples were collected from
      the ileostomy effluent before closure of ileostomy and two after the procedure
      including the first bowel movement. All samples were cultured for  C. difficile
      and analyzed for toxins A and B by a Premier EIA test. Demographic data and
      possible confounding factors were observed and recorded. Twenty-fine adult
      patients were recruited to this study; five patients were subsequently excluded.
      Two patients had positive stool cultures  for C. difficile in the postoperative
      samples and another patient developed clinical pseudomembranous colitis with
      positive toxin. This indicates a possible colonization rate of 3 to 38 per cent
      (95% confidence interval). Four observed cases out of the 20 subjects taking part
      in this  study would confidently conclude that C. difficile colonization in the
      excluded colon is 6 to 44 per cent, i.e., higher than the incidence in the
      healthy adult population, which is 3 per cent. However, the findings of this
      study prompt larger and well-powered studies to confirm these  findings.

PMID- 22472397
TI  - Clinical analysis of 221 cases of adult choledochal cysts.
AB  - Choledochal cyst, usually recognized as a problem in infants, is increasingly
      reported in adult patients. The aim of this study was to share our experience in
      treating adult patients with choledochal cysts. Two hundred twenty-one adult
      patients with choledochal cysts who were treated  in our hospital from January
      2002 to December 2010 were enrolled. The clinical data were retrospectively
      collected and analyzed. There were 168 Type I, three Type II, three Type III, 26
      Type IV, and 21 Type V cysts. The presentations were nonspecific with 177
      patients having abdominal pain  and a few patients having other rare symptoms
      including back pain, cirrhosis, occupying lesions, or spontaneous rupture. The
      cysts were completely removed in 169 patients, and 36 patients required liver
      resection. There was one death resulting from abdominal bleeding. Morbidity was
      limited  to 27 patients, 11 of whom underwent invasive interventions. Choledochal
      cysts remain an interesting clinical problem. In some adult cases, the diagnosis
      is very difficult. Treatment is type-dependent, complete removal of the cysts is
      widely accepted, and lifelong follow-up for these patients  is recommended.

PMID- 22472398
TI  - Poor prognostic factors after repeat hepatectomy for recurrent hepatocellular
      carcinoma in the modern era.
AB  - The purpose of this study was to determine the poor prognostic factors after
      repeat hepatectomy (Hx) in patients with recurrent hepatocellular carcinoma
      (HCC). Overall survival rates and clinicopathological variables in 112 patients
      with repeat Hx from 1992 to 2010 were compared with  those in 531 patients who
      underwent a primary Hx. To clarify the poor prognosis factors after repeat Hx,
      survival data among 112 patients were univariately and multivariately analyzed.
      Overall survival after repeat Hx was similar for that of the patients who
      underwent a primary Hx. The mean  age of repeat Hx group was significantly
      higher, and a well-preserved liver function was recognized than the primary Hx
      group. Multivariate analysis revealed that: 1) indocyanine green retention rate
      at 15 minutes; 2) disease-free interval; 3) tumor size; 4) portal vein invasion
      at primary  Hx; 5) gender; and 6) estimated blood loss to be an independent and
      significant poor prognostic factors. The overall 3-year postrecurrence overall
      survival rates were 100, 91.3, 59.6, and 0 per cent at risk number (R) R0, R1/2,
      R3, R4, respectively (P < 0.05). Repeat Hx provided  a good compatible prognosis
      with primary Hx. In our findings, five risk factors to predict poor outcomes
      after repeat Hx were useful. Patients with recurrent HCC do not have universally
      poor outcomes, and our simple scoring system using five poor prognostic factors
      could serve to advise the  prognosis and the potential benefit for patient
      selection about repeat Hx.

PMID- 22472399
TI  - Profiling the ethnic characteristics of domestic injuries in children younger
      than age 5 years.
AB  - The home remains a very common location for deadly injuries among children
      younger than 5 years. The aim of this study is to describe the demographic and
      injury characteristics of domestic injuries in children younger than 5 years. The
      National Trauma Data Bank's National Sample Program  data set was queried for
      children younger than 5 years with the injury site classified as home. Bivariate
      analysis was performed to determine unadjusted differences by ethnicity.
      Appropriate weight was applied to the sample to determine accurate national
      estimates. A total of 7,364 children,  representing 32,033 children, were
      analyzed. Overall mortality was 1.6 per cent. Among whites, blacks, Hispanics,
      Asians, and Native Americans, intentional injuries accounted for 6.5, 12.8, 10.2,
      5.2, and 19.0 per cent of all injuries by intent, respectively (P < 0.003). Burn
      injury  was disproportionately higher in blacks (24.1%) followed by Native
      Americans and Asians (15.3 and 11.5%, P = 0.008). On multivariate analysis, black
      ethnicity was associated with increased length of stay. Intentional injuries were
      significantly higher in blacks and Native Americans  with black patients
      sustaining a disproportionately higher proportion of burn injury. Therefore,
      greater attention is needed to provide more effective home safety interventions
      to children among high-risk ethnic groups.

PMID- 22472400
TI  - Laparoscopic repair of giant paraesophageal hernia with synthetic mesh: 45
      consecutive cases.
AB  - Giant paraesophageal hernias (PEHs) are associated with progression of symptoms
      in up to 45 per cent of patients. Recently, many series have reported that
      laparoscopic repair of PEH is technically feasible, effective, and safe. A
      retrospective review of the University of Athens tertiary  care hospitals patient
      database and the patient medical records identified 45 patients who underwent
      elective repair of a giant PEH between 2002 and 2009. Elective laparoscopic
      repair of a giant PEH was attempted in 45 patients who were treated with Gore-Tex
      dual mesh with or without Nissen  fundoplication. They all had a mesh repair.
      Intraoperative complications included one pulmonary embolism and one recurrent
      hernia. The use of a mesh seems to be effective in the treatment of large
      hernias. It appears to offer the benefit of a shorter hospital stay and a quicker
      recovery.

PMID- 22472401
TI  - Single-incision laparoscopic cholecystectomy for day surgery procedure: are we
      prepared?
AB  - Single-incision laparoscopic surgery (SILS) for cholecystectomy is a well
      established procedure and represents the next step in developing the concept of
      fast track surgery. This report describes our experience with SILS
      cholecystectomy in patients that stay overnight. Between February  2009 and July
      2010, patients referred for cholecystectomy to the day surgery unit who agreed to
      undergo SILS were included in a prospective study. All operations were performed
      by the same surgical team specially trained in this type of surgery and the same
      operative technique was used in  all cases. Postoperative pain and nausea were
      assessed using a 10-cm visual analogue scale on a self-completion questionnaire
      on the night of operation and the morning of discharge. A total of 107 patients
      (58% women, mean age 56 years) with symptomatic gallstones were included in the
      study.  SILS was successfully performed in all patients and no patient required
      conversion to an open procedure. There were no significant differences in the
      median visual analogue scale for postoperative pain and nausea between the night
      of surgery and the next morning. The mean length of hospital  stay was 23 hours,
      and 98 per cent of patients were satisfied with the results of surgery and would
      be willing to undergo the same procedure again. SILS cholecystectomy is a valid
      alternative to standard laparoscopic cholecystectomy as an outpatient surgery or
      overnight stay procedure. According  to these promising results, SILS
      cholecystectomy could be included in a major ambulatory surgery program.

PMID- 22472402
TI  - Breast cancer tumor size assessment with mammography, ultrasonography, and
      magnetic resonance imaging at a community based multidisciplinary breast center.
AB  - Paramount to staging and patient management is accurately measuring the size of
      invasive breast cancers. We assessed the accuracy of mammography (MG),
      ultrasonography (US), and magnetic resonance imaging (MRI) at our community-based
      hospital in which multiple radiologists and imaging  machines are used in the
      care of our patients. We performed a retrospective analysis of a prospectively
      maintained database of 277 patients seen at our breast center from 2009 to 2010.
      We tabulated MG, US, and MRI-reported tumor sizes in 161 women with pathology
      proven invasive breast cancer  and compared the preoperative size measurements
      with final pathologic tumor size. In the 161 patients, 169 lesions were
      identified. Imaging using all three modalities was available in 47 patients. When
      compared with final pathology, MRI had a correlation of r = 0.75 to mean tumor
      size as compared  with US (r = 0.67) and MG (r = 0.76). Mean tumor size was 1.90
      cm by MG, 1.87 cm by US, 2.40 cm by MRI, and 2.19 cm by pathology. We were able
      to achieve an excellent correlation of pathologic tumor size to preoperative
      imaging. The absolute differences in size between the modalities were  small.
      MRI, in select patients, added to the assessment of tumor size based on US and
      MG.

PMID- 22472403
TI  - Single-incision laparoscopic surgery for partial gastrectomy in patients with a
      gastric submucosal tumor.
AB  - Since 2010, we have used single-incision laparoscopic surgery (SILS) for patients
      with a gastric submucosal tumor, as a less invasive alternative to conventional
      laparoscopy. From September 2010 to January 2011, five patients underwent a local
      resection for a gastric submucosal tumor  using a SILSTM port at Keio University
      Hospital. We performed partial gastrectomy via the SILSTM port using a 5 mm
      flexible endoscope, a vessel sealing system, and a stapling device. There were no
      major intraoperative complications, conversion to laparotomy, or cases of tumor
      rapture.  The average operative time was 89 (range, 72-129) minutes with minimal
      blood loss. Pathological examination revealed four cases of gastrointestinal
      stromal tumor and one case of inflammatory fibrosis caused by nonspecific
      inflammation. Although we examined only a small number of cases  in this study,
      the results suggested that SILS gastrectomy can be performed safely and
      effectively for gastrointestinal stromal tumor.

PMID- 22472404
TI  - Yield of selective magnetic resonance imaging in preoperative workup of newly
      diagnosed breast cancer patients planned for breast conserving surgery.
AB  - The role of routine preoperative magnetic resonance imaging (MRI) in newly
      diagnosed breast cancer patients planned for breast conserving surgery is
      presently being debated. In our medical center we practice selective use of
      preoperative MRI; we sought to examine the yield of MRI in  this highly selected
      group of patients. A retrospective study of all newly diagnosed breast cancer
      patients presenting between January 2007 and July 2010 to the Tel Aviv Sourasky
      Medical Center (Tel Aviv, Israel) was completed. Patients planned for breast
      conserving surgery who underwent preoperative  MRI were included in this study.
      Patients and tumor characteristics, indication for MRI, findings on MRI,
      consequent workup, and impact on surgical treatment were recorded. Association
      between preoperative characteristics and yield of MRI was examined. During the
      study period, 105 patients  that were candidates for breast conserving surgery
      underwent preoperative evaluation with MRI. Use of breast MRI increased over
      time. Rates of mastectomy were stable throughout the study years. Dense mammogram
      was the most frequent (51, 68%) indication for MRI. Additional suspicious
      findings  were found in 41 (39%) patients, prompting further workup including 36
      biopsies in 25 patients, of which 22 (61%) were with cancer. These additional
      findings prompted a change in the surgical plan in a third of the patients. In
      most patients (92; 88%) clear margins were achieved. Limiting  the use of MRI in
      the preoperative workup of breast cancer patients to a selected group of patients
      can increase the yield of MRI.

PMID- 22472405
TI  - Hepatocellular carcinomas and primary liver tumors as predictive factors for
      postoperative mortality after liver resection: a meta-analysis of more than
      35,000 hepatic resections.
AB  - Liver resection is considered the therapeutic gold standard for primary and
      metastatic liver neoplasms. The reduction of postoperative complications and
      mortality has resulted in a more aggressive approach to hepatic malignancies. For
      the most part, results of liver surgery have been  published by highly
      experienced institutions, but the observations of highly specialized units
      results may not reflect the current status of hepatic surgery, underestimating
      mortality and complications. The objective of this study is to evaluate morbidity
      and mortality as a result of liver  resection for primary and metastatic lesions,
      analyzing a large number of studies with a meta-analytic process taking into
      account the overdispersion of data. An extensive literature search has been
      conducted, and 148 papers published between January 2000 and April 2008,
      including a total  of 36,629 patients from both high-volume and low volume
      institutions, were included in the meta-analysis. A beta binomial model was used
      to provide a robust estimate of the summary event rate by pooling overdispersion
      binomial data from different studies. Overall morbidity and mortality after 
      liver surgery were 29.32 per cent and 3.15 per cent, respectively. Significantly
      higher postoperative mortality was observed after liver resection for
      hepatocellular carcinomas and primary hepatic tumors. The application of a beta
      binomial model to correct for overdispersion of liver surgery  data showed
      significantly higher postoperative mortality rates in patients with
      hepatocellular carcinomas or primary hepatic tumors after liver resection.

PMID- 22472406
TI  - Qualitative assessment of the inferior vena cava: useful tool for the evaluation
      of fluid status in critically ill patients.
AB  - Inferior vena cava (IVC) diameter change on limited transthoracic echocardiogram
      (LTTE) can provide a useful guide of fluid status evaluation in critically ill
      patients. Institutional review board approval was obtained. Prospective
      evaluation of hemodynamic status was performed in hypotensive  patients via LTTE.
      Images were obtained using an ultrasound machine without M-mode capability.
      Qualitative assessment of the IVC was obtained via subxyphoid window. FLAT IVC
      was defined as diameter less than 2 cm and FAT IVC when the vein was equal or
      larger than 2 cm. Collapsibility was assessed  by observing respiratory variation
      of the vessel. Lactate was measured before and after therapy was initiated. A
      follow-up LTTE was obtained after fluid challenge. A total of 108 LTTE were
      performed. Patients' age ranged from 18 to 89 years with an average of 53.
      Admission diagnosis was blunt  trauma in 66 patients, penetrating trauma in 17,
      whereas 25 had nontraumatic intra-abdominal emergency. Sixty-nine patients were
      receiving mechanical ventilation at time of LTTE. Seventy-three patients had a
      FLAT IVC, and received fluid challenge as therapy. All patients had a change in
      IVC  volume from "FLAT" to "FAT" after the fluid challenge. Seventy-one patients
      (97%) had resolution of hypotension after the first fluid challenge. Two patients
      had persistent hypotension and received a second fluid challenge. Follow-up LTTE
      demonstrated a FAT IVC and  lack of collapsibility. Lactate decreased in all 73
      patients after therapy guided by LTTE (P < 0.00001) Evaluation of the IVC
      diameter via LTTE offers a rapid, non invasive way to evaluate fluid status in
      critically ill patients.

PMID- 22472407
TI  - The proximal margin of resected hilar cholangiocarcinoma: the effect of
      microscopic positive margin on long-term survival.
AB  - Achieving an R0 resection can be difficult for hilar cholangiocarcinoma (HC)
      because of the anatomic structures of the hepatic hilum and frequent tumor
      infiltration. The aim of this study was to evaluate the margin status of bile
      duct resected in HC and prognostic impact of R1 resection.  Between 2000 and
      2009, 245 patients underwent operation for HC at Asan Medical Center. We
      retrospectively analyzed the clinicopathologic features and surgical outcomes,
      focusing on the proximal margin status, of 162 cases of patients with curative
      intention. Curative resections were achieved  in 125 (52.1%) patients, and R1
      resections were performed in 43 (26.5%). Proximal ductal margin states were
      classified as free margin (73.5%), carcinoma in situ (3.7%), and invasive
      carcinoma (22.8%). The 3- and 5-year survival rates of the R1 group (39.5% and
      34.9%) were not significantly  different from the rates of the R0 group (55.5%
      and 44.5%, respectively). Multivariate analysis showed lymph node metastasis (P =
      0.001) and histologic differentiation (P = 0.001) were independent predictors of
      patient survival. The aggressive surgical approach based on liver  resection
      including caudate lobe may increase the number of patients eligible for a
      curative chance and improve long-term survival even if the microscopically
      positive margin is still achieved.

PMID- 22472408
TI  - Thin chest wall is an independent risk factor for the development of pneumothorax
      after chest tube removal.
AB  - The factors contributing to the development of pneumothorax after removal of
      chest tube thoracostomy are not fully understood. We hypothesized that
      development of post pull pneumothorax (PPP) after chest tube removal would be
      significantly lower in those patients with thicker chest  walls, due to the
      "protective" layer of adipose tissue. All patients on our trauma service who
      underwent chest tube thoracostomy from July 2010 to February 2011 were
      retrospectively reviewed. Patient age, mechanism of trauma, and chest Abbreviated
      Injury Scale score were analyzed.  Thoracic CTs were reviewed to ascertain chest
      wall thickness (CW). Thickness was measured at the level of the nipple at the
      midaxillary line, as perpendicular distance between skin and pleural cavity.
      Chest X-ray reports from immediately prior and after chest tube removal were
      reviewed for  interval development of PPP. Data are presented as average +/-
      standard deviation. Ninety-one chest tubes were inserted into 81 patients.
      Patients who died before chest tube removal (n = 11), or those without thoracic
      CT scans (n = 13) were excluded. PPP occurred in 29.9 per cent of chest  tube
      removals (20/67). When PPP was encountered, repeat chest tube was necessary in 20
      per cent of cases (4/20). After univariate analysis, younger age, penetrating
      mechanism, and thin chest wall were found to be significant risk factors for
      development of PPP. Chest Abbreviated Injury Scale  score was similar in both
      groups. Logistic regression showed only chest wall thickness to be an independent
      risk factor for development of PPP.

PMID- 22472409
TI  - Identifying factors predictive of surgical-site infections after colectomy for
      fulminant ulcerative colitis.
AB  - Surgical-site infections (SSIs) remain a major source of morbidity after
      colectomy for fulminant ulcerative colitis (UC). Identifying UC patients at
      elevated risk of developing SSIs might improve postoperative outcomes. Our goal
      was to identify preoperative factors, which could predict  SSI development in the
      postoperative UC population. The records of 59 patients treated by colectomy for
      fulminant UC from 2004 to 2009 were retrospectively reviewed and statistically
      analyzed. Few differences were observed between patients who developed
      postoperative complications and those  who did not. Twenty patients sustained a
      total of 27 complications, with superficial SSIs being the single most common
      event. Multivariate analysis identified diabetes, white blood cell count > 15
      cells/mm(3), intraoperative blood loss > 200 cc, and intraoperative blood
      transfusion  to all be independent predictors for the development of
      postoperative SSIs. These four factors were all able to independently predict
      SSIs. Postoperative UC patients with these risk factors might benefit from
      heightened wound surveillance or closer follow-up.

PMID- 22472410
TI  - Surgical stress response and clinical outcomes of single port laparoscopic
      cholecystectomy: prospective nonrandomized study.
AB  - The levels of interleukin-6 (IL-6) are proportionate to injury; it is the most
      commonly used quantitative marker in surgical studies. Cytokines and the acute
      phase response play an important role in controlling the human immune system. The
      objective of this study was to compare the  systemic acute cytokine response and
      clinical outcomes of conventional laparoscopic and single port laparoscopic
      cholecystectomy. We compared patients who underwent single port laparoscopic
      cholecystectomy (the single port group) with patients who underwent conventional
      laparoscopic cholecystectomy  (the conventional group) according to the clinical
      variables, IL-6, leukocyte subpopulations, and visual analog scale (VAS) pain
      score. The mean age in the single port group was significantly younger (P =
      0.010) and the mean operation time in the conventional group was significantly 
      shorter (P = 0.002). Postoperative 4-hour VAS pain score was slightly worse in
      the single port laparoscopic cholecystectomy group, but was not significantly
      different. We found no difference in clinical outcomes, the level of serum IL-6,
      C-reactive protein, leukocyte subpopulations,  and complications between the two
      groups. Stress response in single port laparoscopic cholecystectomy is equal to
      conventional surgery. Postoperative 4-hour VAS pain score was slightly worse and
      the operation time is significantly longer in the single port laparoscopic
      cholecystectomy group.

PMID- 22472411
TI  - Incidental left-sided gallbladder during laparoscopic cholecystectomy for
      cholelithiasis.

PMID- 22472412
TI  - The role of a complete blood count with differential for the surgeon.

PMID- 22472413
TI  - A prospective, randomized, single-blind comparison of laparoscopic versus open
      colectomy for slow-transit constipation.

PMID- 22472414
TI  - Sacral osteomyelitis: an unusual complication from foreign body ingestion.

PMID- 22472415
TI  - Old age is a risk factor for recurrence after laparoscopic inguinal hernia repair
      with porcine small intestine submucosa mesh.

PMID- 22472416
TI  - When is vagus nerve-preserving gastrectomy for gastric cancer safe?

PMID- 22472417
TI  - Hepatocellular adenoma: a rare benign tumor of the liver.

PMID- 22472418
TI  - Creating illicit laparoscopic appendectomy ORs using online sourcing.

PMID- 22472419
TI  - Literature survey on epidemiology and pathology of cardiac fibroma.
AB  - BACKGROUND: Although cardiac fibroma has been regarded as benign tumor, it
      presents various symptoms and may lead to death. Unfortunately, only a few
      studies have reported the epidemiology, embryology, and histopathology of the
      tumor, and the factors predicting poorer outcome are still obscured. METHODS: In
      July 2011 we searched for English and Japanese cases of cardiac fibroma using the
      PubMed and IgakuChuoZasshi databases. We then extracted and sampled raw data from
      the selected publications in accordance with the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) style as much as was possible.
      RESULTS: Details of a total of 178 patients with cardiac fibroma were retrieved.
      The mean age was 11.4 years (median: 2.8 years). Tumor sizes ranged from 8.0 to
      150.0 mm (mean 53.1 mm). The left ventricle was found to be the most common site
      associated with the tumor at a rate of 57.3%, followed by the right ventricle,
      and interventricular septum. The highest mortality was found in patients with
      septal involvement (58.6%). In all, 111 patients survived among the 160 patients
      with a recorded outcome. A younger age of the patient at the time of diagnosis
      was associated with a decreased survival rate. In addition, a significant
      positive association was found between ages for patients younger than 17 years of
      age and the diameter of the tumor at the time of diagnosis (r = 0.341, P =
      0.006). CONCLUSIONS: Both the younger age of patients at the time of diagnosis
      and septal involvement can be regarded as factors significantly indicating a poor
      prognosis. Furthermore, our statistical analyses support the following
      hypotheses. First, the high ratio of tumor-to-heart size may generate low cardiac
      output and therefore lead to poor outcome. Second, the ratio of the sites where
      cardiac fibroma occurred corresponds with the ratio of the muscular weight of the
      cardiac chamber. Third, cardiac fibroma involving the interventricular septum
      more frequently induces conduction system disease.

PMID- 22472421
TI  - Structure-based identification of new high-affinity nucleosome binding sequences.
AB  - The substrate for the proteins that express genetic information in the cell is
      not naked DNA but an assembly of nucleosomes, where the DNA is wrapped around
      histone proteins. The organization of these nucleosomes on genomic DNA is
      influenced by the DNA sequence. Here, we present a structure-based computational
      approach that translates sequence information into the energy required to bend
      DNA into a nucleosome-bound conformation. The calculations establish the
      relationship between DNA sequence and histone octamer binding affinity. In silico
      selection using this model identified several new DNA sequences, which were
      experimentally found to have histone octamer affinities comparable to the highest
      affinity sequences known. The results provide insights into the molecular
      mechanism through which DNA sequence information encodes its organization. A
      quantitative appreciation of the thermodynamics of nucleosome positioning and
      rearrangement will be one of the key factors in understanding the regulation of
      transcription and in the design of new promoter architectures for the purposes of
      tuning gene expression dynamics.

PMID- 22472420
TI  - An examination of the electrostatic interactions between the N-terminal tail of
      the Brome Mosaic Virus coat protein and encapsidated RNAs.
AB  - The coat protein of positive-stranded RNA viruses often contains a positively
      charged tail that extends toward the center of the capsid and interacts with the
      viral genome. Electrostatic interaction between the tail and the RNA has been
      postulated as a major force in virus assembly and stabilization. The goal of this
      work is to examine the correlation between electrostatic interaction and amount
      of RNA packaged in the tripartite Brome Mosaic Virus (BMV). Nanoindentation
      experiment using atomic force microscopy showed that the stiffness of BMV virions
      with different RNAs varied by a range that is 10-fold higher than that would be
      predicted by electrostatics. BMV mutants with decreased positive charges
      encapsidated lower amounts of RNA while mutants with increased positive charges
      packaged additional RNAs up to ~900 nt. However, the extra RNAs included
      truncated BMV RNAs, an additional copy of RNA4, potential cellular RNAs, or a
      combination of the three, indicating that change in the charge of the capsid
      could result in several different outcomes in RNA encapsidation. In addition,
      mutant with specific arginines changed to lysines in the capsid also exhibited
      defects in the specific encapsidation of BMV RNA4. The experimental results
      indicate that electrostatics is a major component in RNA encapsidation but was
      unable to account for all of the observed effects on RNA encapsidation.
      Thermodynamic modeling incorporating the electrostatics was able to predict the
      approximate length of the RNA to be encapsidated for the majority of mutant
      virions, but not for a mutant with extreme clustered positive charges. Cryo
      electron microscopy of virions that encapsidated an additional copy of RNA4
      revealed that, despite the increase in RNA encapsidated, the capsid structure was
      minimally changed. These results experimentally demonstrated the impact of
      electrostatics and additional restraints in the encapsidation of BMV RNAs, which
      could be applicable to other viruses.

PMID- 22472422
TI  - Evolvability of yeast protein-protein interaction interfaces.
AB  - The functional importance of protein-protein interactions indicates that there
      should be strong evolutionary constraint on their interaction interfaces.
      However, binding interfaces are frequently affected by amino acid replacements.
      Change due to coevolution within interfaces can contribute to variability but is
      not ubiquitous. An alternative explanation for the ability of surfaces to accept
      replacements may be that many residues can be changed without affecting the
      interaction. Candidates for these types of residues are those that make
      interchain interaction only through the protein main chain, beta-carbon, or
      associated hydrogen atoms. Since almost all residues have these atoms, we
      hypothesize that this subset of interface residues may be more easily substituted
      than those that make interactions through other atoms. We term such interactions
      "residue type independent." Investigating this hypothesis, we find that nearly a
      quarter of residues in protein interaction interfaces make exclusively interchain
      residue-type-independent contacts. These residues are less structurally
      constrained and less conserved than residues making residue-type-specific
      interactions. We propose that residue-type-independent interactions allow
      substitutions in binding interfaces while the specificity of binding is
      maintained.

PMID- 22472423
TI  - Crystal structure of Bacillus subtilis signal peptide peptidase A.
AB  - Signal peptide peptidase A (SppA) is a membrane-bound self-compartmentalized
      serine protease that functions to cleave the remnant signal peptides left behind
      after protein secretion and cleavage by signal peptidases. SppA is found in
      plants, archaea and bacteria. Here, we report the first crystal structure of a
      Gram-positive bacterial SppA. The 2.4-A-resolution structure of Bacillus subtilis
      SppA (SppA(BS)) catalytic domain reveals eight SppA(BS) molecules in the
      asymmetric unit, forming a dome-shaped octameric complex. The octameric state of
      SppA(BS) is supported by analytical size-exclusion chromatography and multi-angle
      light scattering analysis. Our sequence analysis, mutagenesis and activity assays
      are consistent with Ser147 serving as the nucleophile and Lys199 serving as the
      general base; however, they are located in different region of the protein, more
      than 29 A apart. Only upon assembling the octamer do the serine and lysine come
      within close proximity, with neighboring protomers each providing one-half of the
      catalytic dyad, thus producing eight separate active sites within the complex,
      twice the number seen within Escherichia coli SppA (SppA(EC)). The SppA(BS) S1
      substrate specificity pocket is deep, narrow and hydrophobic, but with a polar
      bottom. The S3 pocket, which is constructed from two neighboring proteins, is
      shallower, wider and more polar than the S1 pocket. A comparison of these pockets
      to those seen in SppA(EC) reveals a significant difference in the size and shape
      of the S1 pocket, which we show is reflected in the repertoire of peptides the
      enzymes are capable of cleaving.

PMID- 22472424
TI  - Contiguous deletion of SLC6A8 and BAP31 in a patient with severe dystonia and
      sensorineural deafness.
AB  - We report here a 6-year-old boy exhibiting severe dystonia, profound intellectual
      and developmental disability with liver disease, and sensorineural deafness. A
      deficient creatine peak in brain (1)H-MR spectroscopy and high ratio of
      creatine/creatinine concentration in his urine lead us to suspect a creatine
      transporter (solute carrier family 6, member 8; SLC6A8) deficiency, which was
      confirmed by the inability to take up creatine into fibroblasts. We found a large
      ~19 kb deletion encompassing exons 5-13 of SLC6A8 and exons 5-8 of the B-cell
      receptor-associated protein (BAP31) gene. This case is the first report in which
      the SLC6A8 and BAP31 genes are both deleted. The phenotype of BAP31 mutations has
      been reported only as a part of Xq28 deletion syndrome or contiguous ATP-binding
      cassette, sub-family D, member 1 (ABCD1)/DXS1375E (BAP31) deletion syndrome [MIM
      ID #300475], where liver dysfunction and sensorineural deafness have been
      suggested to be attributed to the loss of function of BAP31. Our case supports
      the idea that the loss of BAP31 is related to liver dysfunction and hearing loss.

PMID- 22472425
TI  - Intracellular glutathione protects human monocyte-derived macrophages from
      hypochlorite damage.
AB  - AIMS: Macrophages must function in an inflammatory environment of high oxidative
      stress due to the production of various oxidants. Hypochlorous acid (HOCl) is a
      potent cytotoxic agent generated by neutrophils and macrophages within
      inflammatory sites. This study determines whether glutathione is the key factors
      governing macrophage resistance to HOCl. MAIN METHODS: Human monocyte derived
      macrophages (HMDM) were differentiated from human monocytes prepared from human
      blood. The HMDM cells were exposed to micromolar concentrations of HOCl and the
      timing of the cell viability loss was measured. Cellular oxidative damage was
      measured by loss of glutathione, cellular ATP, tyrosine oxidation, and
      inactivation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). KEY FINDINGS:
      HOCl causes a rapid loss in HMDM cell viability above threshold concentrations.
      The cell death occurred within 10 min of treatment with the morphological
      characteristics of necrosis. The HOCl caused the extensive cellular protein
      oxidation with the loss of tyrosine residue and inactivation of GAPDH, which was
      accompanied with the loss of cellular ATP. This cellular damage was only observed
      after the loss of intracellular GSH from the cell. Removal of intracellular GSH
      with diethyl maleate (DEM) increased the cells' sensitivity to HOCl damage while
      protecting the intracellular GSH pool with the antioxidant 7,8-dihydroneopterin
      prevented the HOCl mediated viability loss. Variations in the HOCl LD(50) for
      inducing cell death were strongly correlated with initial intracellular GSH
      levels. SIGNIFICANCE: In HMDM cells scavenging of HOCl by intracellular
      glutathione is sufficient to protect against oxidative loss of key metabolic
      functions within the cells.

PMID- 22472426
TI  - Optimization of the preparation process of biological sludge adsorbents for
      application in water treatment.
AB  - The objective of this study was to optimize the preparation of treatment plant
      wastewater sludge adsorbents for application in water treatment. The optimal
      adsorption capacity was obtained with adsorbents prepared by pyrolysis at 700
      degrees C for 3h. We studied the effect of binder type on the adsorbents, finding
      that their textural properties were not substantially affected by the addition of
      phenolic resins but their surface area was reduced by the presence of clayey
      soil. Analysis of the composition of surface groups in these materials revealed:
      (i) a high concentration of basic surface groups in non-activated pyrolyzed
      sludge, (ii) an increase in the concentration of basic surface groups after
      chemical activation, (iii) no modification in the concentration of carboxyl or
      basic groups with the addition of binding agent before the activation, and (iv)
      total disappearance of carbonyl groups from sample surfaces with the addition of
      humic acid or clayey soil as binder. All these adsorbents had a low C content.
      The capacity of these sludge-derived materials to adsorb methylene blue, 2,4
      dichlorophenol, tetracycline, and (Cd(II)) was studied. Their adsorption capacity
      was considerably increased by the chemical activation but reduced by the pre
      activation addition of a binding agent (humic acid, phenolic resin, and clayey
      soil).

PMID- 22472427
TI  - Chemically modified polymer beads for sorption of gold from waste gold solution.
AB  - A simple method to convert gold from waste gold solutions used in chemical
      laboratories and chemical industries into metallic gold nano particles using
      styrene maleic acid copolymer beads has been approached. The styrene maleic acid
      copolymer beads with an average bead diameter 400-600 microns, exhibiting
      exceptionally high rough surface was used as a polymer matrix for the reducing
      gold from aqueous solution to metallic nano gold. Uptake of gold ions from
      aqueous waste gold solution was attempted in a batch process. Conversion of gold
      to metallic nano gold was achieved without the use of any external reducing
      agents. The metallic nano gold particles could be embedded into polymer matrix
      within 2h. The beads exhibited high temperature resistance and could sustain upto
      400 degrees C.

PMID- 22472428
TI  - Synthesis of crescent aromatic oligoamides with preorganized chelating groups and
      their extraction towards transition metal ions.
AB  - Three crescent aromatic oligoamides 1-3 with their backbones rigidified by
      intramolecular hydrogen bonds were designed and synthesized. The liquid-liquid
      extraction by these compounds has been investigated using UV-vis spectrometry
      towards Pb(2+) picrate and some transition metal picrates including Ag(+),
      Hg(2+), Cd(2+), Zn(2+), Cu(2+), Co(2+), Ni(2+) salts. The results revealed higher
      selectivity and efficiency towards Hg(2+) over other metal cations; pentameric
      ligand 1 with six oxygen donor atoms provided the highest extractability of
      83.3%, while dimeric ligand 3 extracted almost exclusively Hg(2+). The
      stoichiometry of the extracted complex between ligand 1 and Hg(2+), and the
      extraction constant (logK(ex)) were determined in solvent extraction.

PMID- 22472429
TI  - Phenol removal efficiencies of sewage treatment processes and ecological risks
      associated with phenols in effluents.
AB  - Phenols pose a risk to the environment and to human health. Phenols found in
      rivers mainly originate from sewage treatment plants (STPs). In this paper,
      analytical procedures, based on deconvolution technology and retention time
      locking technology, were investigated to simultaneously identify and determine
      the concentrations of fifty different phenols in sewage water and effluents.
      Seventeen different phenols were found in sewage and five - including two
      regulated phenols (phenol and 2,4,6-trichlorophenol) and three un-regulated
      phenols (2-chlorophenol, 2,5-dichlorophenol and 2,4-dichloro-3-ethyl-6
      nitrophenol) - were identified in effluents of five STPs. A number of processes
      undertaken in five STPs were also investigated. These processes can be used to
      remove phenols at efficiency levels of between 88.95% and 99.97%. Among the
      processes tested, a combination of anaerobic/anoxic/oxic (A(2)/O), continuous
      microfiltration (CMF), ozone oxidation (O(3)), and chlorination, appeared to be
      the best option for the removal of key phenols. Among the five phenols identified
      in effluents, 2,5-dichlorophenol (1.89 MUg/L) and 2,4-dichloro-3-ethyl-6
      nitrophenol (22.6 MUg/L) pose the greatest ecological risk to receiving waters.

PMID- 22472430
TI  - An ectopic stromal implant model for hematopoietic reconstitution and in vivo
      evaluation of bone marrow niches.
AB  - In adults, hematopoiesis takes places in the bone marrow, where specialized
      niches containing mesenchymal nonhematopoietic cells (stroma) harbor the
      hematopoietic stem cell (HSC). These niches are responsible and essential for the
      maintenance of HSCs. Attempts to expand HSCs fail to  keep the general properties
      of stem cells, which depend on several niche components difficult to reproduce in
      in vitro culture systems. Here, we describe a methodology for in vivo study of
      hematopoietic stroma. We use stroma-loaded macroporous microcarriers implanted in
      the subcutaneous tissue  of experimental animals and show that the ectopic stroma
      implant (ESI) is able to support hematopoiesis. Moreover, lethally irradiated
      mice can be rescued by ESI preloaded with HSCs, showing that they function as an
      ectopic bone marrow. ESI is also shown as a good system to study the role  of
      different niche components. As an example, we used stromas lacking connexin 43
      (Cx43) and confirm the importance of this molecule in the maintenance of the HSC
      niche in vivo. We believe ESI can work as an ectopic bone marrow allowing in vivo
      testing of different niches components and opening  new avenues for the treatment
      of a variety of hematologic conditions particularly when stromal cell defects are
      the main cause of disease.

PMID- 22472431
TI  - Pericardial involvement in diseases of the heart and other contiguous structures:
      part I: pericardial involvement in infarct pericarditis and pericardial
      involvement following myocardial infarction.
AB  - Active contiguous abnormalities can frequently involve the pericardium. Prominent
      among these are cardiac conditions which encroach on the pericardium,
      particularly transmural myocardial infarction (newly always with Q-waves).
      Complications of infarctions, notably myocardial pseudoaneurysm, have one wall
      which is pericardium. Furthermore, dissecting aneurysm of the aorta and the
      intramural aortic hemorrhage may rupture into the pericardium with tamponade, or,
      if limited, mimic acute pericarditis. Diseases of the lungs and pleura, including
      the diaphragmatic pleura, also result in pulmonary embolism which can produce
      several syndromes. Many mediastinal diseases, notably inflammation and
      malignancy, especially involving the lymph nodes, induce mediastinal inflammation
      and fibrosis. Many esophageal disorders can penetrate or produce a fistula
      usually with pneumopericardium. Rarely, primarily pericardial disorders like
      purulent pericarditis, malignancies, and rough pericardial calcifications affect
      the contiguous tissues. We discuss the many syndromes and disorders under each of
      these topics.

PMID- 22472432
TI  - A microplate technique to simultaneously assay calcium accumulation in
      endoplasmic reticulum and SERCA release of inorganic phosphate.
AB  - Traditional analyses of calcium homeostasis have separately quantified either
      calcium accumulation or release mechanisms. To define the system as a whole,
      however, requires multiple experimental techniques to examine both accumulation
      and release. Here we describe a technique that couples the simultaneous
      quantification of radio-labeled calcium accumulation in endoplasmic reticulum
      (ER) microsomes with the release of inorganic phosphate (Pi) by the hydrolytic
      activity of sarco-endoplasmic reticulum calcium ATPase (SERCA) all in the
      convenience of a 96-well format.

PMID- 22472433
TI  - Therapeutic effect of orally administered microencapsulated oxaliplatin for
      colorectal cancer.
AB  - Colorectal cancer is a significant source of morbidity and mortality in the
      United States and other Western countries. Oral delivery of therapeutics remains
      the most patient accepted form of medication. The development of an oral delivery
      formulation for local delivery of chemotherapeutics in the gastrointestinal tract
      can potentially alleviate the adverse side effects including systemic
      cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral
      formulation of the chemotherapeutic drug oxaliplatin for the treatment of
      colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive
      chitosan-coated alginate microspheres. The microparticles were formulated to
      release the chemotherapeutics after passing through the acidic gastric
      environment thus targeting the intestinal tract. In vivo, these particles
      substantially reduced the tumor burden in an orthotopic mouse model of colorectal
      cancer, and reduced mortality.

PMID- 22472434
TI  - Bilateral multifocal Warthin's tumors in upper neck lymph nodes. Report of a case
      and brief review of the literature.
AB  - Cystadenolymphomas (Warthin's tumors) are the second most frequent lesions of the
      parotid gland. Due to their benign clinical behavior, the low rates of recurrence
      and malignant transformation they were classified as tumor-like lesions. In
      addition, a polyclonal growth of the epithelial components of the tumor could be
      detected. Warthin's tumors occur bilateral in 7-10%, whereas a multifocal
      appearance is extremely rare. Even if the pathogenesis is still unclear a
      heterotopia of salivary tissue during embryogenesis is the most likely
      explanation for the origin of these tumors in the upper neck and periparotideal
      region. Here we present a rare case of bilateral, multifocal, extraglandular
      Warthin's tumors in lymph nodes of the upper neck and give a brief review of the
      literature. If a primary malignancy can be excluded by a careful staging
      procedure prior to the operation an isolated excision of the lesions of the neck
      is the adequate treatment.

PMID- 22472435
TI  - Ewald Weibel: an organelle of his very own, and more. Interview by Caitlin
      Sedwick.

PMID- 22472436
TI  - The enduring enigma of nuclear translation.
AB  - Although the physical separation of transcription in the nucleus and translation
      in the cytoplasm has presided as a fundamental tenet of cell biology for decades,
      it has not done so without recurring challenges and contentious debate. In this
      issue, David et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201112145)
      rekindle the controversy by providing convincing experimental evidence for
      nuclear translation.

PMID- 22472437
TI  - Breaking the ties that bind: new advances in centrosome biology.
AB  - The centrosome, which consists of two centrioles and the surrounding
      pericentriolar material, is the primary microtubule-organizing center (MTOC) in
      animal cells. Like chromosomes, centrosomes duplicate once per cell cycle and
      defects that lead to abnormalities in the number of centrosomes result in genomic
      instability, a hallmark of most cancer cells. Increasing evidence suggests that
      the separation of the two centrioles (disengagement) is required for centrosome
      duplication. After centriole disengagement, a proteinaceous linker is established
      that still connects the two centrioles. In G2, this linker is resolved
      (centrosome separation), thereby allowing the centrosomes to separate and form
      the poles of the bipolar spindle. Recent work has identified new players that
      regulate these two processes and revealed unexpected mechanisms controlling the
      centrosome cycle.

PMID- 22472438
TI  - Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to
      prevent polyspermy.
AB  - The mouse zona pellucida is composed of three glycoproteins (ZP1, ZP2, and ZP3),
      of which ZP2 is proteolytically cleaved after gamete fusion to prevent
      polyspermy. This cleavage is associated with exocytosis of cortical granules that
      are peripherally located subcellular organelles unique to ovulated eggs. Based on
      the cleavage site of ZP2, ovastacin was selected as a candidate protease. Encoded
      by the single-copy Astl gene, ovastacin is an oocyte-specific member of the
      astacin family of metalloendoproteases. Using specific antiserum, ovastacin was
      detected in cortical granules before, but not after, fertilization. Recombinant
      ovastacin cleaved ZP2 in native zonae pellucidae, documenting that ZP2 was a
      direct substrate of this metalloendoprotease. Female mice lacking ovastacin did
      not cleave ZP2 after fertilization, and mouse sperm bound as well to Astl-null
      two-cell embryos as they did to normal eggs. Ovastacin is a pioneer component of
      mouse cortical granules and plays a definitive role in the postfertilization
      block to sperm binding that ensures monospermic fertilization and successful
      development.

PMID- 22472439
TI  - Nuclear translation visualized by ribosome-bound nascent chain puromycylation.
AB  - Whether protein translation occurs in the nucleus is contentious. To address this
      question, we developed the ribopuromycylation method (RPM), which visualizes
      translation in cells via standard immunofluorescence microscopy. The RPM is based
      on ribosome-catalyzed puromycylation of nascent chains immobilized on ribosomes
      by antibiotic chain elongation inhibitors followed by detection of puromycylated
      ribosome-bound nascent chains with a puromycin (PMY)-specific monoclonal antibody
      in fixed and permeabilized cells. The RPM correlates localized translation with
      myriad processes in cells and can be applied to any cell whose translation is
      sensitive to PMY. In this paper, we use the RPM to provide evidence for
      translation in the nucleoplasm and nucleolus, which is regulated by infectious
      and chemical stress.

PMID- 22472440
TI  - An extended gamma-tubulin ring functions as a stable platform in microtubule
      nucleation.
AB  - gamma-Tubulin complexes are essential for microtubule (MT) nucleation. The gamma
      tubulin small complex (gamma-TuSC) consists of two molecules of gamma-tubulin and
      one molecule each of Spc97 and Spc98. In vitro, gamma-TuSCs oligomerize into
      spirals of 13 gamma-tubulin molecules per turn. However, the properties and
      numbers of gamma-TuSCs at MT nucleation sites in vivo are unclear. In this paper,
      we show by fluorescence recovery after photobleaching analysis that gamma-tubulin
      was stably integrated into MT nucleation sites and was further stabilized by
      tubulin binding. Importantly, tubulin showed a stronger interaction with the
      nucleation site than with the MT plus end, which probably provides the basis for
      MT nucleation. Quantitative analysis of gamma-TuSCs on single MT minus ends
      argued for nucleation sites consisting of approximately seven gamma-TuSCs with
      approximately three additional gamma-tubulin molecules. Nucleation and anchoring
      of MTs required the same number of gamma-tubulin molecules. We suggest that a
      spiral of seven gamma-TuSCs with a slight surplus of gamma-tubulin nucleates MTs
      in vivo.

PMID- 22472441
TI  - Migrating fibroblasts reorient directionality by a metastable, PI3K-dependent
      mechanism.
AB  - Mesenchymal cell migration as exhibited by fibroblasts is distinct from amoeboid
      cell migration and is characterized by dynamic competition among multiple
      protrusions, which determines directional persistence and responses to spatial
      cues. Localization of phosphoinositide 3-kinase (PI3K) signaling is thought to
      play a broadly important role in cell motility, yet the context-dependent
      functions of this pathway have not been adequately elucidated. By mapping the
      spatiotemporal dynamics of cell protrusion/retraction and PI3K signaling
      monitored by total internal reflection fluorescence microscopy, we show that
      randomly migrating fibroblasts reorient polarity through PI3K-dependent branching
      and pivoting of protrusions. PI3K inhibition did not affect the initiation of
      newly branched protrusions, nor did it prevent protrusion induced by
      photoactivation of Rac. Rather, PI3K signaling increased after, not before, the
      onset of local protrusion and was required for the lateral spreading and
      stabilization of nascent branches. During chemotaxis, the branch experiencing the
      higher chemoattractant concentration was favored, and, thus, the cell reoriented
      so as to align with the external gradient.

PMID- 22472442
TI  - Actin polymerization stabilizes alpha4beta1 integrin anchors that mediate
      monocyte adhesion.
AB  - Leukocytes arrested on inflamed endothelium via integrins are subjected to force
      imparted by flowing blood. How leukocytes respond to this force and resist
      detachment is poorly understood. Live-cell imaging with Lifeact-transfected U937
      cells revealed that force triggers actin polymerization at upstream alpha4beta1
      integrin adhesion sites and the adjacent cortical cytoskeleton. Scanning electron
      microscopy revealed that this culminates in the formation of structures that
      anchor monocyte adhesion. Inhibition of actin polymerization resulted in cell
      deformation, displacement, and detachment. Transfection of dominant-negative
      constructs and inhibition of function or expression revealed key signaling steps
      required for upstream actin polymerization and adhesion stabilization. These
      included activation of Rap1, phosphoinositide 3-kinase gamma isoform, and Rac but
      not Cdc42. Thus, rapid signaling and structural adaptations enable leukocytes to
      stabilize adhesion and resist detachment forces.

PMID- 22472443
TI  - Multivariate proteomic profiling identifies novel accessory proteins of coated
      vesicles.
AB  - Despite recent advances in mass spectrometry, proteomic characterization of
      transport vesicles remains challenging. Here, we describe a multivariate
      proteomics approach to analyzing clathrin-coated vesicles (CCVs) from HeLa cells.
      siRNA knockdown of coat components and different fractionation protocols were
      used to obtain modified coated vesicle-enriched fractions, which were compared by
      stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative
      mass spectrometry. 10 datasets were combined through principal component analysis
      into a "profiling" cluster analysis. Overall, 136 CCV-associated proteins were
      predicted, including 36 new proteins. The method identified >93% of established
      CCV coat proteins and assigned >91% correctly to intracellular or endocytic CCVs.
      Furthermore, the profiling analysis extends to less well characterized types of
      coated vesicles, and we identify and characterize the first AP-4 accessory
      protein, which we have named tepsin. Finally, our data explain how sequestration
      of TACC3 in cytosolic clathrin cages causes the severe mitotic defects observed
      in auxilin-depleted cells. The profiling approach can be adapted to address
      related cell and systems biological questions.

PMID- 22472444
TI  - First biological images with high-energy proton microscopy.
AB  - High-energy proton microscopy provides unique capabilities in penetrating
      radiography including the combination of high spatial resolution and field-of
      view, dynamic range of density for measurements, and reconstructing density
      variations to less than 1% inside volumes and in situ environments. We have
      recently proposed to exploit this novel proton radiography technique for image
      guided stereotactic particle radiosurgery. Results of a first test for imaging
      biological and tissue-equivalent targets with high-energy (800 MeV) proton
      microscopy are presented here. Although we used a proton microscope setup at ITEP
      (Moscow, Russia) optimized for fast dynamic experiments in material research, we
      could reach a spatial resolution of 150 MUm with approximately 10(10) protons per
      image. The potential of obtaining high-resolution online imaging of the target
      using a therapeutic proton beam in the GeV energy region suggests that high
      energy proton microscopy may be used for image-guided proton radiosurgery.

PMID- 22472445
TI  - Spherical crystallization of drugs.
AB  - Spherical crystallization of drugs is the process of obtaining larger particles
      by agglomeration during crystallization. The most common techniques used to
      obtain such particles are spherical agglomeration and quasi-emulsion solvent
      diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are
      extensions of these techniques. By controlling process parameters during
      crystallization, such as temperature, stirring rate, type and amount of solvents,
      or excipient selection, it is possible to control the formation of agglomerates
      and obtain spherical particles of the desired size, porosity, or hardness.
      Researchers have reported that the particles produced have improved micromeritic,
      physical, and mechanical properties, which make them suitable for direct
      compression. In some cases, when additional excipients are incorporated during
      spherical crystallization, biopharmaceutical parameters including the
      bioavailability of drugs can also be tailored.

PMID- 22472446
TI  - Synthesis and potential biological activity of some novel 3-[(N-substituted indol
      3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles and 3,6
      diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles.
AB  - Starting from N-substituted indole-3-carboxaldehydes (1a-g) a series of new 3-[(N
      substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5
      carbonitriles (3a-g and 4a-g) have been synthesized via the acid catalyzed
      condensation reaction of 1a-g with 3-amino-5-pyrazolone, followed by the reaction
      with arylidene malononitriles. A series of new 3,6-diamino-4-(N-substituted indol
      3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles (7a-g) have been prepared either via
      the base catalyzed condensation reaction of 1a-g with 3-amino-5-pyrazolone to
      give 6a-g, followed by the reaction with malononitrile or by the reaction of N
      substituted-3-indolylidene malononitriles (5a-g) with 3-amino-5-pyrazolone.
      According to the obtained results, the newly synthesized compounds possess
      significant anti-inflammatory, analgesic and anticonvulsant activities. The
      anticonvulsant potency of certain tested compounds was more pronounced than both
      anti-inflammatory and analgesic activities. Moreover, most of the newly
      synthesized compounds possess potential antimicrobial activity against
      Escherichia coli and Pseudomonas aeruginosa.

PMID- 22472447
TI  - Optimization of self-assembling properties of fatty acids grafted to methoxy
      poly(ethylene glycol) as nanocarriers for etoposide.
AB  - The objective of this work was to study the effect of fatty acid chain length
      grafted to methoxy poly(ethylene glycol) (mPEG) on self assembling properties of
      micelles for etoposide delivery. Three amphiphilic copolymers were synthesized
      using mPEG, myristic acid, stearic acid and behenic acid through an esteric
      linkage. The particle size and zeta potential of the micelles were determined by
      the dynamic light scattering method. Etoposide was loaded into micelles by film
      casting using various drug/polymer ratios. Drug release was studied by the
      dialysis method. The structure of copolymers was confirmed by (1)H NMR and FTIR.
      Central micellar concentration (CMC) measurements showed that the longer
      hydrophobic chains formed more thermodynamically stable micelles. Among the
      prepared copolymers, etoposide showed the highest solubility in the mPEG-behenic
      copolymer. Drug loading efficiency depended on the hydrophobic chain length and
      drug/polymer ratio. The highest drug loading efficiency was found in mPEG
      myristic micelles with 1:20 drug/polymer ratio. Micelles released 80 % of loaded
      drug within about 5 h.

PMID- 22472448
TI  - Simple RP-HPLC method for determination of triple drug combination of valsartan,
      amlodipine and hydrochlorothiazide in human plasma.
AB  - A simple RP-HPLC method for the quantification of valsartan (VAL), amlodipine
      (AML) and hydrochlorothiazide (HCT) in human plasma was developed and validated.
      VAL, AML and HCT were resolved using a Gemini C18 column and mobile phase
      gradient starting from 20 % acetonitrile and 80 % 10 mmol L(-1) ammonium formate
      (V/V, pH 3.5 +/- 0.2, by formic acid) to 70 % acetonitrile and 30 % 10 mmol L(-1)
      ammonium formate, over 20 minutes, with a flow rate of 1 mL min(-1). The samples
      were purified by protein precipitation and extraction. Telmisartan was used as
      internal standard. The method was validated according to USFDA and EMEA
      guidelines with good reproducibility and linear responses R = 0.9985 (VAL),
      0.9964 (AML), and 0.9971 (HCT). RSDs of intra- and inter-day precision ranged 2.2
      8.1 and 4.6-11.7 %, respectively, for all three drugs. Mean extraction recoveries
      of three QCs for the triple drug combination were 76.5 (VAL), 72.0 (AML) and 73.0
      (HCT) % for human plasma. Although the LC-MS/MS method is more sensitive than
      HPLC, HPLC is still suitable for preliminary pharmacokinetic study. The
      experiments performed demostrated that simultaneous determination of all
      components of the triple drug combination in human plasma can be done by this
      method. Proposed method can be also used for guidance to the LC-MS/MS method.

PMID- 22472449
TI  - Development and characterization of thermosensitive pluronic-based metronidazole
      in situ gelling formulations for vaginal application.
AB  - The purpose of this study was to develop pluronic-based in situ gelling
      formulations of metronidazole (MTZ) for treatment of bacterial vaginosis, aimed
      at prolonging the residence time, controlling drug release, enhancing efficacy,
      decreasing recurrence, and increasing patient compliance. The in situ gel
      formulations were prepared using different concentrations of pluronic F-127 (PF
      127) alone and in combination with pluronic F-68 (PF-68). The prepared
      formulations were evaluated for their gelation temperature (T(gel)), in vitro
      drug release, rheological properties, mucoadhesion properties and tolerability by
      vaginal mucosa in tissue levels. The T(gel) decreased with increasing PF-127
      concentration. The T(gel) was modulated by addition of PF-68 to be within the
      acceptable range of 25-37  degrees C. With increasing pluronic concentration, the
      in vitro drug release decreased, viscosity and mucoadhesive force increased.
      Histopathological examination of rabbit vaginas from the control and treated
      groups revealed normal histology of the vagina and cervix. Based on the in vitro
      evaluation of prepared formulations, the in situ gelling liquid formulated with
      PF-127/PF-68 (20/10 %, m/m) was selected for further clinical evaluation.

PMID- 22472450
TI  - Eudraginated polymer blends: a potential oral controlled drug delivery system for
      theophylline.
AB  - Sustained release (SR) dosage forms enable prolonged and continuous deposition of
      the drug in the gastrointestinal (GI) tract and improve the bioavailability of
      medications characterized by a narrow absorption window. In this study, a new
      strategy is proposed for the development of SR dosage forms for theophylline
      (TPH). Design of the delivery system was based on a sustained release
      formulation, with a modified coating technique and swelling features aimed to
      extend the release time of the drug. Different polymers, such as Carbopol 71G
      (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their
      combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m)
      dispersion of Eudragit (EUD) in order to get the desired sustained release
      profile over a period of 24 h. Various formulations were evaluated for
      micromeritic properties, drug concentration and in vitro drug release. It was
      found that the in vitro drug release rate decreased with increasing the amount of
      polymer. Coating with EUD resulted in a significant lag phase in the first two
      hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to
      decreased water uptake, and hence decreased driving force for drug release.
      Release became faster in the alkaline pH of simulated intestinal fluid (SIF)
      owing to increased solubility of both the coating and matrixing agents. The
      optimized formulation was subjected to in vivo studies in rabbits and the
      pharmacokinetic parameters of developed formulations were compared with the
      commercial (Asmanyl((r))) formulation. Asmanyl((r)) tablets showed faster
      absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value
      of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p <
      0.05) higher than those for Asmanyl((r)), revealing relative bioavailability of
      about 136.93 %. Our study demonstrated the potential usefulness of eudraginated
      polymers for the oral delivery of the sparingly soluble drug theophylline.

PMID- 22472451
TI  - Stability studies of chitosan-DNA-FAP-B nanoparticles for gene delivery to lung
      epithelial cells.
AB  - A successful gene delivery system requires efficiency and stability during
      storage. Stability studies are imperative for nanomedicines containing
      biotechnological products such as plasmids and targeting peptides. Chitosan-DNA
      FAP-B nanoparticles are novel non-viral vectors for specific gene delivery to the
      lung epithelial cells. In this study, the storage stability of chitosan-DNA-FAP-B
      nanoparticles at -20, 5 and 24  degrees C was examined. Size, zeta potential and
      transfection efficiency of these nano-particles in storage were also evaluated.
      Stability studies showed that chitosan-DNA-FAP-B nanoparticles were stable after
      1 month when stored at -20  degrees C and retained their initial size, zeta
      potential and transfection efficiency. However, their stability was not desirable
      at 5 and 24  degrees C. Based on these results, it can be concluded that chitosan
      DNA-FAP-B nanoparticles can be a promising candidate for gene delivery to lung
      epithelial cells with good storage stability at -20  degrees C during 1 month.

PMID- 22472452
TI  - Design and evaluation of moxifloxacin hydrochloride ocular inserts.
AB  - The objective of the present investigation was to prepare and evaluate ocular
      inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of
      moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the
      film casting method. The ocular insert (5.5 mm diameter) was cross-linked by
      CaCl2 and was coated with Eudragit S-100, RL-100, RS-100, E-100 or L-100. The in
      vitro drug drainage/permeation studies were carried out using an all-glass
      modified Franz diffusion cell. The drug concentration and mucoadhesion time of
      the ocular insert were found satisfactory. Cross-linking and coating with
      polymers extended the drainage from inserts. The cross-linked ocular insert
      coated with Eudragit RL-100 showed maximum drug permeation compared to other
      formulations.

PMID- 22472453
TI  - Formulation and evaluation of delayed-onset extended-release tablets of
      metoprolol tartrate using hydrophilic-swellable polymers.
AB  - In view of the circadian rhythm of cardiovascular diseases, a delayed-onset
      extended-release (DOER) formulation of metoprolol tartrate (MT) was prepared.
      This was achieved through dissolution-guided optimization of the proportion of
      Methocel K4M and Methocel K15M. Core erosion ratio was greater than 50 %, thereby
      showing steady release of the drug after the lag time until complete dissolution.
      Optimized formulation produced a lag phase of 6 h followed by complete release of
      98.7 +/- 2.1 % in 24 h. Water uptake study revealed that Methocel K15M has lower
      water uptake (30 +/- 1 %) than Methocel K4M (40 +/- 2 %) after 24 h. Axial
      swelling of polymers was higher than swelling in the radial direction. Drug
      polymer interaction study precludes any interaction between drug and polymer.
      Such a drug delivery system may provide a viable alternative for effective
      management of hypertension and other related disorders. This work also proposes
      an approach to attain DOER for a hydrophilic drug by using a hydrophilic
      swellable polymer in press coat.

PMID- 22472454
TI  - Antioxidant supplementation and serum lipids in patients with Graves' disease:
      effect on LDL-cholesterol.
AB  - The effect of supplementation with a fixed combination of antioxidants (beta
      carotene, selenium, vitamins C and E) on serum lipids was monitored in patients
      with newly detected Graves' disease. Measurements were made prior to the
      commencement of therapy and after 30 and 60 days. Patients were randomized into
      two groups. Test group comprised patients who received antioxidant
      supplementation in addition to methimazole, while patients treated with
      methimazole only were in the control group. The concentration of total and HDL
      cholesterol increased significantly in test and control groups (p < 0.05) but
      these groups did not differ significantly. Concentration of LDL-cholesterol
      increased significantly in the test group only (p < 0.005) and was significantly
      different from the control group 60 days after the commencement of therapy (p <
      0.005). Significant increase in the LDL-cholesterol concentration in the test
      group requires further investigations.

PMID- 22472455
TI  - Reconsidering metabolic diseases: the impacts of persistent organic pollutants.

PMID- 22472457
TI  - Dose-modified XELIRI chemotherapy for metastatic colorectal cancer--a
      retrospective study of 78 patients.

PMID- 22472456
TI  - Herpes simplex virus type 2 (HSV-2) as a coronary atherosclerosis risk factor in
      HIV-infected men: multicenter AIDS cohort study.
AB  - We assessed associations of herpes simplex virus types 1 and 2 (HSV-1 and -2),
      cytomegalovirus (CMV), and human herpesvirus 8 (HHV-8) infection with subclinical
      coronary atherosclerosis in 291 HIV-infected men in the Multicenter AIDS Cohort
      Study. Coronary artery calcium (CAC) was measured by non-contrast coronary CT
      imaging. Markers for herpesviruses infection were measured in frozen specimens
      collected 10-12 years prior to case identification. Multivariable logistic
      regression models and ordinal logistic regression models were performed. HSV-2
      seropositivity was associated with coronary atherosclerosis (adjusted odds ratio
      [AOR]=4.12, 95% confidence interval [CI]=1.58-10.85) after adjustment for age,
      race/ethnicity, cardiovascular risk factors, and HIV infection related factors.
      Infection with a greater number of herpesviruses was associated with elevated CAC
      levels (AOR=1.58, 95% CI=1.06-2.36). Our findings suggest HSV-2 may be a risk
      factor for subclinical coronary atherosclerosis in HIV-infected men. Infection
      with multiple herpesviruses may contribute to the increased burden of
      atherosclerosis.

PMID- 22472458
TI  - Lemierre's syndrome due to Klebsiella pneumoniae in a 63-year-old man with
      diabetes: a case report.
AB  - INTRODUCTION: Lemierre's syndrome was originally documented to be caused by
      Fusobacterium necrophorum. It is a very rare condition with a prevalence of one
      to 14.4 instances per million. Its presentation is varied, not only in
      composition but also in the infecting organism. Treatment with anticoagulants has
      been controversial and applied only on a case-by-case basis. CASE PRESENTATION: A
      63-year-old Saudi man who had had uncontrolled diabetes mellitus for 47 years
      presented to our facility with a five-day history of swelling on the right side
      of his neck and fever. The swelling progressively increased in size and was
      associated with pain, dysphagia, odynophagia, change of voice ('hot potato
      voice'), and reduced appetite. Abscess content culture and sensitivity testing
      revealed Klebsiella pneumoniae. However, blood culture results were repeatedly
      negative. The abscess was incised and drained without any complication. Our
      patient was treated with clindamycin and cefuroxime. Warfarin was also
      administered concurrently for six weeks, for an isolated internal jugular vein
      thrombosis (IJV), with complete resolution of the thrombus. Normoglycemia was
      achieved and our patient was discharged after complete wound healing and the
      return of his biochemical parameters to normal. CONCLUSIONS: Only two cases of
      Lemierre's syndrome in patients with diabetes due to K. pneumoniae have been
      reported previously. A review of the literature suggested that an association
      exists between deep neck infections due to K. pneumoniae and diabetes mellitus.
      The reasons for this association are still not clear. This poses a question as to
      whether diabetes mellitus specifically predisposes these patients to infection
      with this organism. It is suggested that clinicians should consider infectious
      agents other than F. necrophorum in the causation of Lemierre's syndrome,
      especially in patients with diabetes.

PMID- 22472460
TI  - Atlanto-axial instability in achondroplastic dwarfs: a report of two cases and
      literature review.
AB  - BACKGROUND: Achondroplasia is the commonest form of human dwarfism. The authors
      report atlanto-axial instability, in consequence to os odontoideum in this
      subgroup of patients. METHODS: Two achondroplastic dwarfs harboring atlanto-axial
      dislocation are described along with radiological findings. RESULTS: Both
      children underwent successful internal rigid immobilization, using sublaminar
      atlanto-axial wiring. CONCLUSIONS: Craniovertebral junction instability should be
      evaluated among these children, whenever foramen magnum insufficiency is being
      considered.

PMID- 22472461
TI  - Pericardial involvement in diseases of the heart and other contiguous structures:
      part II: pericardial involvement in noncardiac contiguous disorders.
AB  - Active contiguous abnormalities can frequently involve the pericardium. Prominent
      among these are cardiac conditions which encroach on the pericardium,
      particularly transmural myocardial infarction (newly always with Q-waves).
      Complications of infarctions, notably myocardial pseudoaneurysm, have one wall
      which is pericardium. Furthermore, dissecting aneurysm of the aorta and the
      intramural aortic hemorrhage may rupture into the pericardium with tamponade, or,
      if limited, mimic acute pericarditis. Diseases of the lungs and pleura, including
      the diaphragmatic pleura, also result in pulmonary embolism which can produce
      several syndromes. Mediastinal diseases, notably inflammation and malignancy,
      especially involving the lymph nodes, induce mediastinal inflammation and
      fibrosis. Many esophageal disorders can penetrate or produce a fistula usually
      with pneumopericardium. Rarely, primarily pericardial disorders like purulent
      pericarditis, malignancies, and rough pericardial calcifications affect the
      contiguous tissues. We discuss the many syndromes and disorders under each of
      these topics.

PMID- 22472459
TI  - Male risk taking, female odors, and the role of estrogen receptors.
AB  - Male risk-taking and decision making are affected by sex-related cues, with men
      making riskier choices and decisions after exposure to either women or stimuli
      associated with women. In non-human species females and, or their cues can also
      increase male risk taking. Under the ecologically relevant condition of predation
      threat, brief exposure of male mice to the odors of a sexually receptive novel
      female reduces the avoidance of, and aversive responses to, a predator. We
      briefly review evidence showing that estrogen receptors (ERs), ERalpha and
      ERbeta, are associated with the mediation of these risk taking responses. We show
      that ERs influence the production of the female odors that affect male risk
      taking, with the odors of wild type (ERalphaWT, ERbetaWT), oxytocin (OT) wildtype
      (OTWT), gene-deleted 'knock-out' ERbeta (ERbetaKO), but not ERalphaKO or oxytocin
      (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of
      male mice to cat odor. We further show that administration of specific ERalpha
      and ERbeta agonists to OVX females results in their odors increasing male risk
      taking and boldness towards a predator. We also review evidence that ERs are
      involved in the mediation of the responses of males to female cues, with ERalpha
      being associated with the sexual and both ERbeta and ERalpha with the sexual and
      social mechanisms underlying the effects of female cues on male risk taking. The
      implications and relations of these findings with rodents to ERs and the
      regulation of human risk taking are briefly considered.

PMID- 22472462
TI  - Outcome of immediate re-operation or interval debulking after chemotherapy at a
      gynecologic oncology center after initially incomplete cytoreduction of advanced
      ovarian cancer.
AB  - BACKGROUND: Prognosis in advanced ovarian cancer is largely determined by
      completeness of tumor resection achieved during primary surgery. Incomplete
      initial debulking occurs frequently in non-specialized centers and there is an
      ongoing discussion about the best time for re-surgery after referral to tertiary
      centers. METHODS: Patients with advanced epithelial ovarian cancer (FIGO IIIB-IV)
      admitted between 1999 and 2007 who had primary incomplete surgery including those
      with initiated chemotherapy at an outside institution were included. Surgical
      results, morbidity and prognosis were evaluated in patients with immediate re
      operation before chemotherapy and those with interval debulking. RESULTS: 48
      eligible patients were identified in our tumor registry. Self-referral by patient
      was the most frequent mode of admission (n=21, 43.8%). 22 patients (45.8%)
      underwent immediate re-surgery and 26 patients (54.2%) had an interval debulking
      after chemotherapy. In 12 patients (54.5%), macroscopically complete tumor
      removal could be achieved by immediate re-operation and in 17 patients (65.4%)
      after chemotherapy. Major complications were observed more frequently in patients
      with interval debulking (26.9 vs. 9.1%, p=0.324). Median overall survival time
      was 53 and 34 months (p=0.110) after immediate and delayed re-operation,
      respectively. CONCLUSIONS: Upfront re-operation before start of chemotherapy is
      feasible and successful in an expertise referral center in more than half of
      patients with incomplete primary surgery elsewhere. Complete resection even after
      initial incomplete debulking could improve outcome. Therefore, referral to
      expertise centers in those patients should be considered. Progression-free
      survival and overall survival showed a non-significant trend and complication
      rate is a remarkable advantage in favor of upfront re-operation.

PMID- 22472463
TI  - Effect of a pelvic floor muscle training program on gynecologic cancer survivors
      with pelvic floor dysfunction: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects of a pelvic floor rehabilitation program
      (PFRP) on pelvic floor function and quality of life (QoL) in gynecological cancer
      survivors in a prospective, randomized, controlled trial. METHODS: Thirty-four
      patients with gynecological cancers recruited between July 2009 and December 2009
      were randomly allocated into two groups: a PFRP group (n=17), who participated in
      a 4-week PFRP exercise program, and a non-PFRP group (n=17), who received the
      usual health care. The pelvic floor strength, the motor evoked potentials (MEPs)
      elicited by sacral and transcranial magnetic stimulation, the pelvic floor
      questionnaire, and the scores on two QoL questionnaires, (QLQ)-C30 and QLQ-CX 24,
      from the European Organization for Research and Treatment of Cancer (EORTC) were
      evaluated to assess changes in pelvic floor function and QoL before and after the
      exercise program. RESULTS: Twenty four patients (12 from each group) completed
      the exercise program. The PFRP group improved in pelvic floor strength (mean
      difference (MD)=14.22, t(9)=2.389, P=0.036) and sexual functioning. The PFRP
      group also improved in physical and sexual function compared with the non-PFRP
      group. CONCLUSIONS: The results suggest that the PFRP improved pelvic floor
      dysfunction and QoL of gynecological cancer patients. A larger randomized
      controlled trial is planned.

PMID- 22472464
TI  - Synergistic antileukemic action of a combination of inhibitors of DNA methylation
      and histone methylation.
AB  - DNA methylation and histone methylation are both involved in epigenetic
      regulation of gene expression and their dysregulation can play an important role
      in leukemogenesis. Aberrant DNA methylation has been reported to silence the
      expression of tumor suppressor genes in leukemia. Overexpression of the histone
      methyltransferase, EZH2, a subunit of the polycomb group repressive complex 2
      (PRC2), was observed to promote oncogenesis. This is due to aberrant gene
      silencing by the trimethylation of histone H3 lysine 27 (H3K27me3) by EZH2. Since
      both these epigenetic silencing events are reversible, they are interesting
      targets for chemotherapeutic intervention by using an inhibitor of DNA
      methylation, such as 5-aza-2'-deoxcytidine (5-AZA-CdR), and 3-deazaneplanocin-A
      (DZNep), an inhibitor of the EZH2. Human HL-60 and murine L1210 leukemic cells
      exposed in vitro to 5-AZA-CdR and DZNep in combination showed a synergistic loss
      of clonogenicity in a colony assay as compared to each agent alone. This positive
      chemotherapeutic interaction was also observed in mice with L1210 leukemia.
      Quantitative PCR showed that the combination also produced a remarkable
      synergistic activation of the tumor suppressor genes, CDKN1A and FBXO32.
      Microarray analysis showed that 5-AZA-CdR plus DZNep produced a synergistic
      activation of >150 genes. Our results indicate that 5-AZA-CdR plus DZNep can
      reactivate target genes that are silenced by two distinct epigenetic mechanisms
      leading to a loss of the proliferative potential of leukemic cells.

PMID- 22472465
TI  - Tiny cystine stones in the gallbladder of a patient with cholecystolithiasis
      complicating acute cholecystitis: a case report.
AB  - Cystine stones, the main component of which is cystine, are very common urinary
      calculi, but are rare in the gall bladder. In animals, there has been only one
      report of cystine gallstones in tree shrews, and to our knowledge, this is the
      first report of cystine gallstones in humans.

PMID- 22472467
TI  - Comparison of reference points in different methods of temporomandibular joint
      imaging.
AB  - PURPOSE: Conventional radiography is a well-established method for imaging of the
      temporomandibular joint (TMJ) structures. However, the dental computer tomography
      becomes more important for the visualization of teeth in the jaw-bone. The
      applicability of dental computer tomography for the visualization of the TMJ it
      not yet been proven. The aim of the study was to identify TMJ structures using
      reference points with the magnetic resonance imaging (MRI) and the computed
      tomography (CT). METHODS: In order to compare the visualization and measurement
      of the TMJ a total of eight human cadaver heads was examined with CT and MRI and
      analysed using reference points. RESULTS: In both imaging techniques the selected
      reference points and distances are well definable and allow objective evaluation
      of anatomical structures. The CT images display a clearly better contrast to
      noise ratio than the MR images. The distance measurement of different width and
      length showed significant correlation of both images techniques. CONCLUSIONS: In
      TMJ diagnostics, maximum information could be obtained using both imaging
      techniques together due to synergistic effects.

PMID- 22472466
TI  - An increased fluid intake leads to feet swelling in 100-km ultra-marathoners - an
      observational field study.
AB  - BACKGROUND: An association between fluid intake and changes in volumes of the
      upper and lower limb has been described in 100-km ultra-marathoners. The purpose
      of the present study was (i) to investigate the association between fluid intake
      and a potential development of peripheral oedemas leading to an increase of the
      feet volume in 100-km ultra-marathoners and (ii) to evaluate a possible
      association between the changes in plasma sodium concentration ([Na+]) and
      changes in feet volume. METHODS: In seventy-six 100-km ultra-marathoners, body
      mass, plasma [Na+], haematocrit and urine specific gravity were determined pre-
      and post-race. Fluid intake and the changes of volume of the feet were measured
      where the changes of volume of the feet were estimated using plethysmography.
      RESULTS: Body mass decreased by 1.8 kg (2.4%) (p < 0.0001); plasma [Na+]
      increased by 1.2% (p < 0.0001). Haematocrit decreased (p = 0.0005). The volume of
      the feet remained unchanged (p > 0.05). Plasma volume and urine specific gravity
      increased (p < 0.0001). Fluid intake was positively related to the change in the
      volume of the feet (r = 0.54, p < 0.0001) and negatively to post-race plasma
      [Na+] (r = -0.28, p = 0.0142). Running speed was negatively related to both fluid
      intake (r = -0.33, p = 0.0036) and the change in feet volume (r = -0.23, p =
      0.0236). The change in the volume of the feet was negatively related to the
      change in plasma [Na+] (r = -0.26, p = 0.0227). The change in body mass was
      negatively related to both post-race plasma [Na+] (r = -0.28, p = 0.0129) and
      running speed (r = -0.34, p = 0.0028). CONCLUSIONS: An increase in feet volume
      after a 100-km ultra-marathon was due to an increased fluid intake.

PMID- 22472468
TI  - The diagnostic value of cytokine and nitric oxide concentrations in cerebrospinal
      fluid for the differential diagnosis of meningitis.
AB  - PURPOSE: In several cases of meningitis routinely used diagnostic procedures are
      unable to identify the cause of this disease. The objective of the present study
      was to determine whether proinflammatory cytokine (tumour necrosis factor (TNF
      alpha), interleukin-1beta (IL-1beta), interleukin-8 (IL-8)) and nitric oxide (NO)
      concentrations in the CSF are useful markers for the differential diagnosis of
      meningitis. MATERIAL AND METHODS: Sixty-seven patients (42 patients with
      bacterial meningitis and 25 patients with viral meningitis) were included in the
      present study. In the investigated group, the TNF-alpha, IL-1beta and IL-8
      concentrations in the CSF samples collected on the day of admission were
      assessed. Furthermore, the NO concentrations were assessed in 23 patients.
      RESULTS: The results revealed that the measurement of proinflammatory cytokines
      in CSF can aid in a differential diagnosis. In particular, a high concentration
      of TNF-alpha may be a sensitive and specific marker of a bacterial aetiology of
      the neuroinfection. In the present study, TNF-alpha concentrations greater than
      75.8 pg/ml differentiated between bacterial and viral meningitis with 100%
      sensitivity and specificity. The NO concentration in the CSF was also
      significantly greater in patients with bacterial meningitis than in those with
      viral meningitis. CONCLUSIONS: The assessment of TNF-alpha, IL-1beta and IL-8
      concentrations in the CSF is useful in the differential diagnosis of
      neuroinfection. Because many factors may influence NO production in the central
      nervous system (CNS), it is not clear whether NO values can be used for the
      differential diagnosis of meningitis, and further studies are required.

PMID- 22472469
TI  - Metabolite alterations in autistic children: a 1H MR spectroscopy study.
AB  - PURPOSE: The purpose of this study was to assess the role of proton magnetic
      resonance spectroscopy (1H MRS) in the detection of changes in cerebral
      metabolite levels in autistic children. MATERIAL AND METHODS: Study group
      consisted of 12 children, aged 8-15 years, who were under the care of Pediatric
      Neurology Department and Pediatric Rehabilitation Department of Medical
      University of Bialystok. The diagnosis of autism was established by neurologist,
      psychiatrist and psychologist in every case. All patients matched the clinical
      criteria of the disease according to International Statistical Classification of
      Diseases and Related Health Problems (ICD-10). The control group included 16
      healthy children aged 7-17. 1H MRS was performed with a single-voxel method (TE
      36, TR-1500, NEX-192). The volume of interest (VOI) was located in the frontal
      lobe regions, separately on each side. RESULTS: We showed lower N
      acetylaspartate/creatine (NAA/Cr), gamma-aminobutyric acid /creatine (GABA/Cr)
      and glutamate/creatine (Glx/Cr) in the frontal lobes in the study group comparing
      with healthy controls. The ratio of myoinositol/creatine (mI/Cr) was increased in
      autistic children. No differences in choline/creatine (Cho/Cr) ratio in study
      group and controls were found. There was a correlation between age and NAA/Cr in
      autistic children (R=0.593 p=0.041). No significant differences in metabolite
      ratios between right and left hemisphere in ASD and controls were found.
      CONCLUSIONS: (1)H MRS can provide important information regarding abnormal brain
      metabolism. Differences in NAA/Cr, GABA/Cr, Glx/Cr and mI/Cr may contribute to
      the pathogenesis of autism.

PMID- 22472470
TI  - Dental caries and total antioxidant status of unstimulated mixed whole saliva in
      patients aged 16-23 years.
AB  - PURPOSE: The purpose of the studies performed was an attempt to establish a
      potential relationship between total antioxidant status of unstimulated whole
      saliva, patients' ages, oral hygiene status and dental caries. MATERIAL AND
      METHODS: The study involved 120 non-smokers. Mean age of the study subjects was
      18.40 +/- 1.74 years. Clinical examination was performed to evaluate the state of
      hard and soft oral tissues, and oral hygiene status. Additionally, biochemical
      tests and statistical studies were carried out. Laboratory examinations involved
      measuring the total antioxidant status level in supernatant using the Total
      Antioxidant Status (TAS) test from Randox. In statistical analysis, Spearman Rang
      correlation coefficient, Kruskal-Wallis test, Mann - Whitney test, logistic
      regression and ROC curve were used. The analysis was conducted using Statistica 9
      software. RESULTS: Mean D, M, F and DMFT values were 4.04 +/- 3.96; 0.09 +/-
      0.34; 5.00 +/- 3.90; 9.05 +/- 5.30, respectively. Mean OHI - S was 0.95 +/- 0.76.
      Mean TAS value in the studied population was 0.82 +/- 0.26 mmol/l. In the group
      of subjects without active dental caries, the level of the total antioxidant
      potential was higher, with a value of 0.89 +/- 0.16 mmol/l, and in the study
      group subjects who had tooth decay it was 0.80 +/- 0.28 mmol/l. It was found that
      TAS was higher in younger subjects. CONCLUSIONS: The conducted studies seem to
      allow for the following conclusions:TAS level in the supernatant of unstimulated
      whole saliva decreases with age; TAS level in the supernatant of unstimulated
      whole saliva is the highest in patients without caries, and the oral hygiene
      status does not have significant influence on TAS.

PMID- 22472471
TI  - Vitamin D status and bone density in steroid-treated children with
      glomerulopathies: effect of cholecalciferol and calcium supplementation.
AB  - PURPOSE: The aim of this study was to assess vitamin D status and bone density in
      steroid-treated children with glomerulopathies and to evaluate the effect of
      prophylactic vitamin D and calcium supplementation. MATERIAL AND METHODS:
      Retrospective analysis was performed on 55 children aged 4-18 yrs with
      glomerulopathies. The following data were analyzed: antropometrical parameters,
      bone densitometries, parathormone, 25-hydroxyvitamin D (25-OHD), urinary calcium
      excretion and medications received for prevention of low bone mass. RESULTS: A
      significant number of children (38%) had decreased spinal bone mineral density
      (BMD z-score < -2.0) and the majority of them (89%) had hypovitaminosis D (25-OHD
      < 30 ng/ml), 75% were vitamin D insufficient (25-OHD < 20 ng/ml) and 16% were
      vitamin D deficient (25-OHD < 10 ng/ml). The mean serum 25-OHD concentration was
      comparable to that of controls (19.32 +/- 12.87 vs. 15.05 +/- 8.52 ng/ml). Nearly
      all patients (82%) were receiving preparations of calcium and/or vitamin D to
      improve bone health. Patients on cholecalciferol had higher mean concentration of
      25-OHD compared to those who were not receiving it (p=0.027) and to the controls
      (p=0.047). In 23 children on vitamin D and calcium supplementation for an average
      6-month time, we observed an increase in the mean BMD values (p=0.004), however,
      mean BMD z-score and 25-OHD concentrations did not significantly change over
      time. CONCLUSIONS: Vitamin D and bone density deficits are remarkably common in
      steroid-treated children with glomerulopathies, despite vitamin D and calcium
      repletion. In order to enhance the effectiveness of vitamin D supplementation for
      improvement of bone density, we suggest regular assessment of serum concentration
      of 25-OHD that can guide subsequent dose adjustment of vitamin D.

PMID- 22472472
TI  - Mesenchymal stem cells and islet cotransplantation in diabetic rats: improved
      islet graft revascularization and function by human adipose tissue-derived stem
      cells preconditioned with natural molecules.
AB  - Hypoxia plays an important role in limiting the engraftment, survival, and
      function of intrahepatically transplanted islets. Mesenchymal stem cells (MSCs)
      were recently used in animal models of islet transplantation not only to reduce
      allograft rejection but also to promote revascularization.  Among different
      possible origins, adipose tissue represents a novel and good source of MSCs.
      Moreover, the capability of adipose tissue-derived stem cells (ASCs) to improve
      islet graft revascularization was recently reported after hybrid transplantation
      in mice. Within this context, we have  previously shown that hyaluronan esters of
      butyric and retinoic acids can significantly enhance the rescuing potential of
      human MSCs (hMSCs). Here we evaluated whether ex vivo preconditioning of human
      ASCs (hASCs) with a mixture of hyaluronic (HA), butyric (BU), and retinoic (RA)
      acids may  result in optimization of graft revascularization after islet/stem
      cell intrahepatic cotransplantation in syngeneic diabetic rats. We demonstrated
      that hASCs exposed to the mixture of molecules are able to increase the secretion
      of vascular endothelial growth factor (VEGF) as well as the transcription  of
      angiogenic genes, including VEGF, KDR (kinase insert domain receptor), and
      hepatocyte growth factor (HGF). Rats transplanted with islets cocultured with
      preconditioned hASCs exhibited a better glycemic control than rats transplanted
      with an equal volume of islets and control hASCs. Cotransplantation  with
      preconditioned hASCs was also associated with enhanced islet revascularization in
      vivo, as highlighted by graft morphological analysis. The observed increase in
      islet graft revascularization and function suggests that our method of stem cell
      preconditioning may represent a novel strategy  to remarkably improve the
      efficacy of islets-hMSCs cotransplantation.

PMID- 22472473
TI  - Ethnomedicine of the Kagera Region, north western Tanzania. Part 3: plants used
      in traditional medicine in Kikuku village, Muleba District.
AB  - BACKGROUND: The Kagera region of north western Tanzania has a rich culture of
      traditional medicine use and practice. Traditional medicines are the mainstay of
      healthcare in this region and are known to support the management of many
      illnesses such as malaria, bacterial infections, epilepsy, gynecological problems
      and others. However, most of the plants being used have either not been
      documented or evaluated for safety and efficacy or both. This study, the sixth of
      an ongoing series, reports on the medicinal plants that are used at Kikuku
      village, Muleba District. METHODOLOGY: A semi-structured questionnaire was used
      to collect information on the common/local names of the plants, parts of the
      plants used, diseases treated, methods of preparing the herbal remedies, dosage
      of the remedies administered, frequency and duration of treatment and toxicity of
      the medicines. A literature review was carried out for information on the
      ethnomedical uses of the reported plants. RESULTS: A total of 49 plant species
      belonging to 47 genera and 24 plant families were documented. The family
      Euphorbiaceae and Asteraceae had the highest representation. The plants are used
      for the treatment of skin conditions (10 plants; 20%), bacterial infections and
      wounds (14 plants; 28.6%), malaria (14 plants; 28.6%), gastrointestinal disorders
      (11 plants; 22.4%), gynecological problems including infertility (8 plants;
      16.3%), hypertension (5 plants; 10.2%), viral infections (7 plants; 14.3%), chest
      problems (5 plants; 10.2%), diabetes (3 plants; 6.1%), cancer (2 plants; 4.1%),
      inflammatory conditions (arthritis, rheumatism), HIV and AIDS, and hernia each
      treated by 1 plant (3 plants in total; 6.1%). Information obtained from the
      literature indicate that 25 (51.0%) of the therapeutic claims are supported by
      laboratory results or have similar claims of ethnomedical use from other
      countries. CONCLUSION: Herbal remedies comprise an important and effective
      component of the healthcare system in Kikuku village with plants in the families
      Euphorbiaceae and Asteraceae comprising an important part of plants used in the
      indigenous healthcare management in the village. Malaria and bacterial infections
      dominate the list of diseases that are managed using traditional medicines.

PMID- 22472474
TI  - Alterations in white matter evident before the onset of psychosis.
AB  - BACKGROUND: Psychotic disorders are associated with widespread reductions in
      white matter (WM) integrity. However, the stage at which these abnormalities
      first appear and whether they are correlates of psychotic illness, as opposed to
      an increased vulnerability to psychosis, is unclear. We addressed these issues by
      using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR)
      of psychosis before and after the onset of illness. METHODS: Thirty-two
      individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode
      schizophrenia were studied using DTI. The UHR subjects and controls were re
      scanned after 28 months. During this period, 8 UHR subjects had developed
      schizophrenia. Between-group differences in fractional anisotropy (FA) and
      diffusivity were evaluated cross sectionally and longitudinally using a
      nonparametric voxel-based analysis. RESULTS: At baseline, WM DTI properties were
      significantly different between the 3 groups (P < .001). Relative to controls,
      first-episode patients showed widespread reductions in FA and increases in
      diffusivity. DTI indices in the UHR group were intermediate relative to those in
      the other 2 groups. Longitudinal analysis revealed a significant group by time
      interaction in the left frontal WM (P < .001). In this region, there was a
      progressive reduction in FA in UHR subjects who developed psychosis that was not
      evident in UHR subjects who did not make a transition. CONCLUSIONS: People at UHR
      for psychosis show alterations in WM qualitatively similar to, but less severe
      than, those in patients with schizophrenia. The onset of schizophrenia may be
      associated with a progressive reduction in the integrity of the frontal WM.

PMID- 22472475
TI  - Curious cases--The curious case of a man with schizophrenia and excessive
      aggression.

PMID- 22472476
TI  - Improved capillary electrophoresis frontal analysis by dynamically coating the
      capillary with polyelectrolyte multilayers.
AB  - An improved CE-FA method using a polyelectrolyte multilayer (PEML) coated
      capillary is described. The coating was simply created by alternatively flushing
      the capillary with positively charged polyelectrolyte polybrene (HDB) and
      negatively charged polyelectrolyte dextran sulfate (DS). Human serum albumin
      (HSA) and 6 drugs were selected as an experimental model to evaluate such an
      improvement. The PEML coating was demonstrated to effectively reduce the protein
      adsorption on the capillary wall. Compared with the uncoated capillary, the
      repeatability (RSD%) of the EOF mobility and the plateau height of free drug were
      improved significantly from 3.7% to 0.51% and from 0.61% to 0.34%, respectively.
      No interference of the coating on the measurement of protein-drug binding
      parameters was observed.

PMID- 22472477
TI  - Penetration of experimental infiltrants with different penetration coefficients
      and ethanol addition into natural caries lesions in primary molars.
AB  - This study evaluated the influence of the penetration coefficient (PC) and
      ethanol addition on the penetration depth (PD) of experimental infiltrants into
      proximal caries lesions in primary molars. Caries lesions (n = 45) were randomly
      treated with 1 of 4 experimental infiltrants (PC63; PC185; PC204; PC391) for 5
      min. Lesion depths and PDs were analysed using dual fluorescence confocal
      microscopy. Lesions were almost completely infiltrated in all groups. Median PDs
      and percentage penetrations were not significantly different between groups (p >
      0.05). When applied for 5 min, all tested infiltrants were able to infiltrate
      proximal caries in primary molars nearly completely.

PMID- 22472478
TI  - Salivary alpha-amylase and cortisol in infancy and toddlerhood: direct and
      indirect relations with executive functioning and academic ability in childhood.
AB  - Using data from a predominantly low-income, population-based prospective
      longitudinal sample of 1292 children followed from birth, indicators of
      children's autonomic (salivary alpha-amylase; sAA) and hypothalamic-pituitary
      adrenal (HPA) axis (salivary cortisol) activity at 7, 15, and 24 months of age
      were found to predict executive functioning at 36-months and academic achievement
      in pre-kindergarten. The findings suggested that the respective cortisol and sAA
      effects on executive functioning and academic achievement were interactive.
      Optimal developmental outcomes were associated with asymmetrical cortisol/sAA
      profiles. Higher cortisol levels were predictive of lower executive functioning
      and academic abilities, but only for those with concurrently moderate to high
      levels of sAA. In contrast, higher sAA concentrations were predictive of better
      executive functioning and academic abilities, but only for those with
      concurrently moderate to low levels of cortisol. These relations were
      statistically identical across infancy and toddlerhood. The conditional effects
      of cortisol and sAA on pre-kindergarten academic achievement were mediated fully
      by links between these early physiological indicators and executive functioning.

PMID- 22472479
TI  - Physiological and behavioural consequences of long-term moderate treadmill
      exercise.
AB  - The benefits of long-term moderate exercise for health are widely accepted in
      humans, but few animal studies have been undertaken to characterize the effects
      of such activity on emotionality and responsiveness to stress. The present study
      describes the effects of long-term moderate forced treadmill training (36 weeks)
      on exploratory activity, anxiety-like behaviour, and the resting or stress levels
      of some physiological variables, including pituitary-adrenal (PA) hormones. Five
      week-old male Sprague-Dawley rats were trained on the treadmill (TM) for 36
      weeks, using a more moderate training (12m/min, 30min/day, 4-5 days/week) than
      that currently used in the literature. Two groups were used as controls: a non
      handled sedentary (SED) group, receiving no manipulation, and a control (CON)
      group exposed to a stationary treadmill for the same amount of time as the TM
      group. In accordance with literature data, TM rats showed lower resting levels of
      glucose, triglycerides and cholesterol than the other two groups. The TM and CON
      groups both showed higher ambulation than the SED group in some behavioural
      tests, without evidence for altered anxiety. Resting levels of
      adrenocorticotropin (ACTH) and corticosterone did not differ among the groups,
      but a reduced ACTH response to both a novel environment (mild stressor) and an
      active escape-avoidance task (severe stressor) was observed in TM rats, whereas
      changes in corticosterone were modest. The results support the view that the
      physiological consequences of long-term moderate training are beneficial,
      including reduced PA responsiveness to stress, even though exercise training did
      not affect anxiety-like behaviour.

PMID- 22472480
TI  - Allogeneic hematopoietic stem cell transplant for adults over 40 years old with
      acquired aplastic anemia.
AB  - Although younger age is associated with favorable prognosis in adults undergoing
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aplastic
      anemia (AA), other pretransplantation factors may be more important than age. We
      retrospectively analyzed the impact of older age on transplantation outcomes and
      survival in a total of 225 adult patients with AA who underwent allo-HSCT: 57
      patients >40 years old (older patient group [OPG]) and 168 patients <=40 years
      old (younger patient group [YPG]). Age at allo-HSCT <=40 years, time from
      diagnosis to allo-HSCT <=6 months, and matched related donor (MRD) were favorable
      prognostic factors in all study patients. Risk analysis of survival in the OPG
      showed that age >50 years was the only poor prognostic factor. Survival did not
      differ significantly between the YPG and patients <50 years old in the OPG. In
      conclusion, patients between the ages of 41 and 50 years with severe AA and MRDs
      should undergo allo-HSCT as early as possible to optimize survival.

PMID- 22472481
TI  - Paroxysmal hypothermia in two patients with multiple sclerosis.
AB  - BACKGROUND: Hypothermia is a rare condition in patients with multiple sclerosis
      (MS). Only 17 patients have been reported so far. CASE REPORT: We report 2
      patients with a long history of MS who presented with severe acute hypothermia
      associated with thrombocytopenia and hepatic cytolysis. Both patients presented
      with an aggravation of their neurological status, psychomotor slowing and
      confusion. There was no clinical or biological sign of infection. Magnetic
      resonance imaging (1.5 T) revealed bilateral preoptic T(2)-weighted lesions for 1
      patient. The neurological status of one patient was worse after the episode of
      hypothermia than before, which suggests that hypothermia could be a factor of
      poor prognosis concerning disease progression.

PMID- 22472482
TI  - Cancer survivor identity shared in a social media intervention.
AB  - This study investigates how cancer survivors construct their identities and the
      impact on their psychological health, as measured by depression and survivor self
      efficacy. Fourteen young adult survivors of pediatric cancer participated in a
      customized social networking and video blog intervention program, the
      LIFECommunity, over a 6-month period. Survivors were asked to share their stories
      on various topics by posting video messages. Those video blog postings, along
      with survey data collected from participants, were analyzed to see how cancer
      survivors expressed their identities, and how these identities are associated
      with survivors' psychosocial outcomes. In survivors who held negative stereotypes
      about cancer survivors, there was a positive relationship with depression while
      positive stereotypes had a marginal association with cancer survivor efficacy.
      Findings indicate that although pediatric cancer survivors often do not publicly
      discuss a "cancer survivor identity," they do internalize both positive and
      negative stereotypes about cancer survivorship. It is important for practitioners
      to be aware of the long-term implications of cancer survivor identity and
      stereotypes.

PMID- 22472483
TI  - Speech pathology services to children with cancer and nonmalignant hematological
      disorders.
AB  - Children with cancer and nonmalignant hematological disorders may require speech
      pathology (SP) support; however, limited evidence is available describing
      prevalence and severity of swallowing/feeding and communication impairments in
      this population. A retrospective chart review of 70 children referred to SP at
      the newly formed Queensland Children's Cancer Centre was conducted to describe
      the prevalence and severity of swallowing/feeding and communication dysfunction,
      and the association between impairment, oncology and hematology diagnosis, and
      service utilization (time and occasions of service). Swallowing/feeding disorders
      were the most commonly observed impairments at initial assessment (58.6%).
      Children with central nervous system tumors (P = .03) and nonmalignant
      hematological disorder (P = .03) had significantly higher rates of feeding
      impairment than other oncology and hematology diagnostic groups. Children with
      central nervous system tumors had the highest rates of oral phase (P = .01) and
      pharyngeal phase (P = .01) dysphagia (swallowing disorder). No significant
      difference was found between diagnostic groups for intensity of SP service
      delivery. Prospective research is required to examine prevalence and severity of
      disorders, and service utilization in a more established clinic, and to
      investigate interactions between cancer treatment and swallowing/feeding and
      communication dysfunction.

PMID- 22472484
TI  - Exploring boundaries in pediatric oncology nursing.
AB  - Professional patient boundaries are an issue that is relevant across all realms
      of nursing practice. By nature, nurses are caring individuals. Therapeutic
      relationships are integral to the care of patients. When caring for patients on a
      daily basis for extended periods of time, it can be difficult for nurses to know
      when their care goes beyond professional boundaries. Providing care to patients
      in a pediatric oncology situation substantially increases this ethical dilemma.
      Length of stay, degree of crisis, embedded relationships, and emotional turmoil,
      along with the nurturing connection between adult and child, are among the
      reasons that boundaries are often blurred within the context of this sensitive
      patient population. This article explores the differences between nursing care,
      boundary crossings, and boundary violations. Strategies to evaluate nursing
      actions for appropriateness, along with reflection and development of individual
      boundaries, are offered. The information presented is relevant not only to
      nursing care of pediatric patients who are facing chronic or life-threatening
      conditions but also to each nurse-client relationship established in nursing
      practice.

PMID- 22472485
TI  - Knowledge of stroke among an urban population in Cotonou (Benin).
AB  - BACKGROUND: Studies on the knowledge of stroke, its related risk factors and
      warning symptoms in the populations of Sub-Saharan Africa are scarce. No study
      has been performed in Benin until now. METHODS: A door-to-door survey was
      performed in two districts of Cotonou with a broad socioeconomic range. 15,155
      individuals aged >=15 years were interviewed using a semi-structured
      questionnaire adapted from previous reports. RESULTS: 15,155 individuals
      consented to participate in the survey. 14.1% correctly identified the brain as
      the affected organ in stroke. The most commonly identified risk factor was
      hypertension (34.5%). The most often cited warning signs of stroke were paralysis
      and hemiplegia (34.4%). Relatives were the major source of information about
      stroke (25.1%). In multivariate analysis, age, education level, occupation, self
      reported risk factors of stroke, overweight and obesity were associated with at
      least one correct response to the questionnaire about stroke risk factors or
      symptoms. CONCLUSION: The awareness of stroke, and its risk factors and symptoms
      is low in Cotonou. The results suggest that specific education programs may
      improve people's knowledge of stroke and their awareness of related risk factors
      in Sub-Saharan African countries.

PMID- 22472486
TI  - Associations between omega-3 poly-unsaturated fatty acids from fish consumption
      and severity of depressive symptoms: an analysis of the 2005-2008 National Health
      and Nutrition Examination Survey.
AB  - Fish is the primary source of dietary omega-3 poly-unsaturated fatty acids EPA
      and DHA, which have been reported to reduce depressive symptoms in clinical
      trials. We assessed the association between fish consumption and depressive
      symptoms in a nationally representative sample of 10,480 adults from the 2005
      2008 National Health and Nutrition Examination Survey. Depressive symptoms were
      classified by severity using the Patient Health Questionnaire. Fish meal
      consumption reported in 30-day food frequency questionnaires, and EPA+DHA intake
      computed from 24-h dietary recalls were evaluated in relation to depressive
      symptoms using multivariable ordinal logistic regression. Consumption of breaded
      fish showed an increased risk of greater depressive symptom severity, while all
      fish, non-breaded fish, and shell fish were not associated. Any EPA+DHA intake
      was significantly associated with fewer depressive symptoms. Exposure-response
      analyses revealed no clear patterns for any intake measures. Inconsistent
      patterns of associations in our study may be partially explained by exposure
      misclassification.

PMID- 22472487
TI  - Computational identification of adaptive mutants using the VERT system.
AB  - : BACKGROUND: Evolutionary dynamics of microbial organisms can now be visualized
      using the Visualizing Evolution in Real Time (VERT) system, in which several
      isogenic strains expressing different fluorescent proteins compete during
      adaptive evolution and are tracked using fluorescent cell sorting to construct a
      population history over time. Mutations conferring enhanced growth rates can be
      detected by observing changes in the fluorescent population proportions. RESULTS:
      Using data obtained from several VERT experiments, we construct a hidden Markov
      derived model to detect these adaptive events in VERT experiments without
      external intervention beyond initial training. Analysis of annotated data
      revealed that the model achieves consensus with human annotation for 85-93% of
      the data points when detecting adaptive events. A method to determine the optimal
      time point to isolate adaptive mutants is also introduced. CONCLUSIONS: The
      developed model offers a new way to monitor adaptive evolution experiments
      without the need for external intervention, thereby simplifying adaptive
      evolution efforts relying on population tracking. Future efforts to construct a
      fully automated system to isolate adaptive mutants may find the algorithm a
      useful tool.

PMID- 22472488
TI  - Comparison of early results of surgical treatment in patients with pancreatic
      cancer.
AB  - Pancreatic tumours are a serious medical and social issue. Patients come to the
      doctor too late, when the disease is well advanced. The most frequently applied
      method of surgical treatment is pancreatoduodenectomy (Whipple procedure). The
      most frequently used technique of pancreatoduodenectomy is the Child-Waugh
      method. The procedure can be performed in a classic way or as modified by
      Traverso (with preservation of the pylorus). MATERIAL AND METHODS: Between August
      2008 and June 2011, in the Department of Thoracic, General and Oncologic Surgery
      of Medical University in Lodz, a total of 79 patients with pancreatic tumours
      were hospitalized. In 61, pancreatoduodenectomy was performed. The patients were
      divided into two groups, depending on the diagnosis and the procedures performed:
      group 1 comprised patients in whom the pylorus was resected (n = 43); group 2
      comprised patients in whom the pylorus was preserved (Traverso-Longmire
      procedure; n = 18). RESULTS: Mean duration of surgery was about 3 hours and 50
      minutes in both groups. Mean duration of hospitalization after the procedure was
      15.6 days in group 1 and 12.2 days in group 2 (p < 0.05). Early complications
      (within 30 days of the procedure) were observed in 33.2% of patients in both
      groups. Blood transfusion was necessary in 21% of patients in group 1 and 28% of
      patients in group 2 (p>0.05). CONCLUSIONS: There are specific indications for
      each method of surgical treatment, however, it seems that both techniques of
      pancreatic resection can be recommended as standard surgical treatment, and the
      number of complications after both procedures is similar.

PMID- 22472489
TI  - The impact of the types of microorganisms isolated from blood and wounds on the
      results of treatment in burn patients with sepsis.
AB  - Despite development of combustiology, infections continue to be the most
      important cause of death among patients with burns. Sepsis is the most severe
      clinical presentation of infection in patients after thermal injuries who require
      immediate treatment. Early diagnosis and proper treatment of sepsis are important
      in the clinical management that is often hampered for multiple reasons, e.g.
      impaired patient immunity, problems with microorganisms with multi-antibacterial
      drug resistance. The aim of the study was to assess effect of type of a
      microorganism isolated from blood and wound on results of treatment of sepsis in
      patients with burns. MATERIAL AND METHODS: Effect of type of microorganisms
      isolated from blood and wound on the result of treatment of sepsis was studied in
      338 patients hospitalized immediately after an injury in Centre for Burn
      Treatment in Siemianowice Slaskie in years 2003 - 2004 (at the age of 18 - 96
      years, 66 women and 272 men). Clinical symptoms of generalized infection were
      found in all study subjects. The study group was divided into two subgroups:
      cured patients and patients who died of sepsis. The following parameters were
      assessed in both subgroups: type of microorganism isolated from blood, type of
      microorganism isolated from wound as well as occurrence of the same and different
      infections of blood and burn wound. RESULTS: positive blood cultures were found
      in 165 patients (48.8%), 106 (64.2%) were cured, 59 (35.8%) died. The most
      commonly isolated microorganisms in cured patients were Gram(+) Staphylococcus
      epidermidis MRSE (19.81%) and Staphylococcus aureus MRSA (18.87%). Gram(-)
      intestinal rods were least commonly isolated from this group. The most commonly
      isolated microorganisms from blood of patients who were to die, included non
      fermenting Gram(-) rods Acinetobacter baumannii (35.59%) and Pseudomonas
      aeruginosa (22.03%). Mixed bacterial flora was found in the blood of 22.03%
      patients. Among patients who were to die, the same microorganisms were found in
      the blood and in the wound in 32.2% of patients, while this rate was 17.92 in
      cured patients. The most commonly found bacteria in the blood and burn wound in
      the cured patients included Staphylococcus aureus MRSA (31.58%) and
      Staphylococcus aureus (21.05%). In the group of patients who were to die, the
      most common bacteria isolated simultaneously from the blood and burn wound
      included Acinetobacter baumannii (47.37%) and Pseudomonas aeruginosa (36.84%).
      CONCLUSIONS: 1. The patients with thermal injuries are at higher risk of death in
      the event of sepsis caused by Gram(-) bacteria versus Gram(+) bacteria. 2.
      Infection of blood and burn wound caused by the same bacteria Pseudomonas
      aeruginosa and Acinetobacter baumanni increases the risk of death due to sepsis
      in patients with burns following thermal injuries.

PMID- 22472490
TI  - Influence of internal carotid endarterectomy on patients' life quality.
AB  - Appropriate treatment of symptomatic carotid artery stenosis can reduce ischemic
      cerebral strokes' risk and in some cases eliminate neurological symptoms.
      Endarterectomy is the most common surgical treatment. The aim of the study was to
      examine the influence of carotid endarterectomy on neurological symptoms and
      patients' life quality. MATERIAL AND METHODS: The material comprised of 102
      patients who underwent endarterectomy. All of the patients were given a
      questionnaire with a list of neurological symptoms (vertigos, headaches, left
      hemiparesis, right hemiparesis, numbness, acroparaesthesia, single syncope,
      recurrent syncopies, diplopia, tinnitus, concentration disturbances and aphasia)
      and with a numerical life quality scale to fill in before and a year after the
      surgery. RESULTS: Vertigo, headache, single and recurrent syncopies and aphasia
      as well as cerebral stroke and amaurosis fugax were significantly more rarely
      observed after endarterectomy. The mean value of patients' life quality evaluated
      on a 10-point Likert scale after the surgery increased (3.9 vs 6.3). CONCLUSIONS:
      A year after carotid endarterectomy patients' life quality improves which is
      connected with neurological symptoms' regression and no further symptoms'
      occurrence due to a preventive role of the surgery.

PMID- 22472491
TI  - Own clinical observations of treatment outcome in acute type B aortic dissection.
AB  - The aim of the study was to analyse early results of treatment of acute type B
      aortic dissection. MATERIAL AND METHODS: 59 patients, treated between 1998 and
      2011, were divided into four groups. Group I comprised ten patients in whom
      hybrid procedures were performed: extra-anatomical by-pass graft from the brachio
      cephalic trunk to the left carotid artery in six patients, transposition of the
      left carotid artery to the right one in two patients, and reversed Y prosthesis
      from the brachio-cephalic trunk to both carotids in the remaining 2 patients, to
      facilitate stent-grafting. Group II comprised 13 patients in whom endovascular
      procedures were performed (stent-grafting). Group III comprised 21 patients in
      whom conventional surgery was done. Group IV comprised 15 patients who were
      treated conservatively. RESULTS: In group I, a very good clinical outcome,
      without complications, was achieved in six patients (60% of cases). The total
      mortality rate was 40%. One patient died on the operation table, following stent
      grafting, due to the rupture of the aortic arch. Two patients died as a result of
      brain damage (cerebral aneurysm rupture in one, and ischemic stroke in the
      other). In one patient, an aorto-oesophageal fistula developed. In group II, one
      patient died during endovascular procedure. Another patient suffered from type 1
      endoleak, requiring repeated endovascular surgery. In group III, 15 patients
      (72%) died. Moreover, four patients required acorrective cardiac surgery (Bentall
      procedure)which in three patients resulted in death. Thus, the total mortality
      rate in this group was as high as 85%. In group IV, the mortality rate was 13%.
      CONCLUSIONS: We noticed a clear superiority of endovascular procedures over
      conventional surgeries-for acute type B aortic dissection. Hybrid procedures for
      acute, complicated type B aortic dissection evidently reduce mortality and
      postoperative morbidity. Uncomplicated acute type B aortic dissections should be
      treated conservatively at intensivecare units.

PMID- 22472492
TI  - Surgical treatment of hyperinsulinism during the course of pancreatic cancer
      (insulinoma) - one center experience.
AB  - Endogenic hyperinsulinism is mainly caused by neuroendocrine tumors (insulinomas)
      which autonomously secrete insulin. Because the symptoms are often aspecific, a
      considerably delay in diagnosis occurs. The treatment consists of operative
      removal of the tumor from the pancreas, preceded by pre-operative localization.
      In this article we describe our experience with surgical removal of insulinomas.
      MATERIAL AND METHODS: We retrospectively analyzed all patients with insulinoma
      which were treated in our center. Definitive diagnosis was made using a 72-hours
      glucoses fasting test. We describe the symptoms, localization techniques and the
      outcomes after surgery. RESULTS: Between January 2002 and May 2011, 45 patients
      (35.6% men and 64.4% female) were treated in our center. The most prevalent
      symptoms were altered consciousness and general malaise. The combination of CT
      scan and endoscopic ultrasound had the highest (90%) sensitivity to localize
      tumors pre-operatively. During surgery, in 40 patients (89%) the tumor could be
      removed by enucleation. In the other five patients partial pancreas resection was
      required. In 22 patients (49%) we used intra-operative insulin level measurements
      to confirm complete tumor resection. Within the first month after surgery, two
      patients (4.4%) developed acute pancreatitis, four patients (8.8%) developed a
      pancreatic fistula. One patient died of multi-organ-failure. All patients were
      free from symptoms of hyperinsulinism after the surgery and after a median follow
      up of 4.5 years. CONCLUSIONS: Based on the experience with 45 patients, surgical
      removal, aided by pre-operative localization with CT and endoscopic
      ultrasonography, is an effective and safe treatment for insulinomas.

PMID- 22472493
TI  - True and pseudocysts of the spleen - a diagnostic and therapeutic problem.
AB  - Splenic cysts are rarely diagnosed lesions. This also includes splenic
      pseudocysts, which usually develop as a result of a blunt abdominal cavity
      injury. Splenic cysts are usually diagnosed on the basis of imaging examinations,
      performed in case of symptomatic patients or those subject to a blunt abdominal
      cavity injury. MATERIAL AND METHODS: The study group comprised six patients with
      a positive history of blunt abdominal cavity trauma, verified by means of
      histopathological examinations, which were subject to surgical intervention at
      the Department of General and Endocrinological Surgery, Medical University in
      Lodz, during the period between 01.01.2006 and 31.12.2010. Before or during the
      surgical procedure cystic lesions were diagnosed. The efficacy of the surgical
      intervention was determined. RESULTS: Splenic pseudocysts were diagnosed in only
      two of the patients, although in all there was a reasonable suspicion of the
      above-mentioned lesion. One patient required three operations, due to recurrence
      of the lesion, which proved to be a primary epithelial cyst. Two of the patients
      required early explorative relaparotomy. Apart from the above-mentioned,
      treatment proved uneventful. CONCLUSIONS: The diagnosis of a splenic pseudocyst
      is established in case of suspicion of the above-mentioned lesion. This is
      evidence that in some patients focal lesions of a different nature are present,
      being detected by means of diagnostic imaging examinations performed after
      abdominal cavity injuries.

PMID- 22472494
TI  - Reconstruction in case of full thickness abdominal wall defects due to
      necrotizing fascitis - case report.
AB  - Emergency full thickness abdominal wall defects constitute a challenging problem
      for surgeons. The aim of reconstruction is prevention of evisceration and hernia
      formation. Staged surgery is recommended in such cases. The first stage consists
      of wound healing with skin grafts and creation of "planned hernia". Ultimate
      reconstruction is delayed until good general health state of the patient. In
      presented case final skin and subcutaneous tissue reconstruction was achieved
      with island fasciocutaneous antero-lateral thigh flap. Reconstruction of musculo
      aponeurotic layer was completed with compartment separation technique and
      synthetic mesh. During follow-up no recurrence of deformity was observed.

PMID- 22472495
TI  - Maxillary reconstruction using a multi-element free fibula flap based on a three
      dimensional polyacrylic resin model.
AB  - Preoperative preparation of working models of the skull and free bone flaps using
      the digital print technology and photocured polyacrylic resins may be of a great
      benefit to the patient, for whom a virtual resection and reconstruction procedure
      may be planned in detail and performed. The purpose of mid-facial reconstruction
      using 3D models is to plan a functional mid-facial reconstruction procedure in
      order to restore supportive function of intraorbital structures and to make
      placement of dental implants and further prosthetic rehabilitation
      possible.Maxillary and mid-facial reconstruction using a free fibula flap based
      on a three-dimensional working model was performed in a patient diagnosed with a
      squamous cell carcinoma of the left maxillary sinus penetrating to the orbit, the
      ethmoid complex, and the pterygopalatine fossa. The use of three-dimensional
      polyacrylic models allowed for detailed preoperative planning and a virtual
      resection and reconstruction procedure with a highly satisfying functional and
      cosmetic effect.A procedure based on methods discussed here may be significantly
      shorter and more precise.

PMID- 22472496
TI  - "Sportsman's hernia". Part one: Pathophysiology, nomenclature and treatment.

PMID- 22472497
TI  - Optimization of two methods based on ultrasound energy as alternative to European
      standards for soluble salts extraction from building materials.
AB  - The Italian recommendation NORMAL 13/83, later replaced by the UNI 11087/2003
      norm, were used as standard for soluble salts extraction from construction
      materials. These standards are based on long-time stirring (72 and 2h,
      respectively) of the sample in deionized water. In this work two ultrasound based
      methods were optimized in order to reduce the extraction time while efficiency is
      improved. The instrumental variables involved in the extraction assisted by
      ultrasound bath and focused ultrasounds were optimized by experimental design. As
      long as it was possible, the same non-instrumental parameters values as those of
      standard methods were used in order to compare the results obtained on a mortar
      sample showing a black crust by the standards and the optimized methods. The
      optimal extraction time for the ultrasounds bath was found to be of two hours.
      Although the extraction time was equal to the standard UNI 11087/2003, the
      obtained extraction recovery was improved up to 119%. The focused ultrasound
      system achieved also better recoveries (up to 106%) depending on the analyte in
      1h treatment time. The repeatabilities of the proposed ultrasound based methods
      were comparables to those of the standards. Therefore, the selection of one or
      the other of the ultrasound based methods will depend on topics such as
      laboratory facilities or number of samples, and not in aspects related with their
      quality parameters.

PMID- 22472498
TI  - Phase-transfer catalytic dichlorocyclopropanation of styrene under the influence
      of ultrasound conditions - A kinetic study.
AB  - The kinetics for dichlorocyclopropanation of styrene with an excess of chloroform
      were studied under phase-transfer catalysis and ultrasound irradiation conditions
      using aqueous sodium hydroxide as the base and benzyltriethylammonium bromide as
      a catalyst. The reaction was carried out at 35 degrees C under pseudo-first order
      conditions by keeping aqueous sodium hydroxide and chloroform in excess and was
      monitored by gas chromatography (GC). The effects of agitation speed, quaternary
      ammonium salts, amount of catalyst, amount of sodium hydroxide and temperature on
      the kinetics of the conversion were investigated.

PMID- 22472499
TI  - Respiratory care year in review 2011: long-term oxygen therapy, pulmonary
      rehabilitation, airway management, acute lung injury, education, and management.
AB  - For the busy clinician, educator, or manager, it is becoming an increasing
      challenge to filter the literature to what is relevant to one's practice and then
      update one's practice based on the current evidence. The purpose of this paper is
      to review the recent literature related to long-term  oxygen therapy, pulmonary
      rehabilitation, airway management, acute lung injury and acute respiratory
      distress syndrome, respiratory care education, and respiratory care management.
      These topics were chosen and reviewed in a manner that is most likely to have
      interest to the readers of Respiratory  Care.

PMID- 22472500
TI  - Imaging of acute respiratory distress syndrome.
AB  - Chest radiography and computed tomography (CT) have a crucial role to play in the
      diagnosis and management of acute respiratory distress syndrome (ARDS). The
      identification of pulmonary opacification is a requirement for the definition of
      ARDS on the chest radiograph, while CT has a  role to play, not only in the
      diagnosis of ARDS, but also in the identification of complications. This paper
      reviews the radiological appearances of ARDS that have been documented for some
      time, and also more recent research that has identified a role for CT in
      directing ventilation and in  prognostication.

PMID- 22472501
TI  - Aerosol delivery device selection for spontaneously breathing patients: 2012.
AB  - Using an electronic literature search for published articles indexed in PubMed
      between January 1990 and August 2011, the update of this clinical practice
      guideline is the result of reviewing 84 clinical trials, 54 reviews, 25 in vitro
      studies, and 7 evidence-based guidelines. The recommendations  below are made
      following the Grading of Recommendations Assessment, Development, and Evaluation
      (GRADE) criteria: 1: It is recommended that selection of the appropriate aerosol
      generator and interface be made based on the patient's age, physical and
      cognitive ability, cost, and the availability  of the prescribed drug for use
      with a specific device. 2: Nebulizers and pressurized metered-dose inhalers
      (pMDIs) with valved holding chambers are suggested for use with children <= 4
      years of age and adults who cannot coordinate the use of pMDI or dry-powder
      inhaler (DPI). 3: It is suggested  that administration of aerosols with DPIs be
      restricted to patients >= 4 years of age who can demonstrate sufficient flow for
      the specific inhaler. 4: For patients who cannot correctly use a mouthpiece,
      aerosol masks are suggested as the interface of choice. 5: It is suggested that
      blow-by  not be used for aerosol administration. 6: It is suggested that aerosol
      therapy be administered with a relaxed and nondistressed breathing pattern. 7:
      Unit dose medications are suggested to reduce the risk of infection. 8: It is
      suggested that nebulizer/drug combinations should be used as  approved by the
      FDA. 9: It is recommended that healthcare providers know the correct use of
      aerosol generators; they should teach and periodically re-teach patients about
      how to use aerosol devices correctly. 10: It is suggested that intermittent
      positive-pressure breathing should not be used  for aerosol therapy. 11: It is
      recommended that either nebulizer or pMDI can be used for aerosol delivery during
      noninvasive ventilation.

PMID- 22472502
TI  - Emergency bedside extracorporeal membrane oxygenation for rescue of acute
      tracheal obstruction.
AB  - A 39-year-old man experienced total obstruction of a distal tracheal plastic
      stent by a tumor mass, preventing effective ventilation and resulting in cardiac
      arrest. Resuscitation by emergency bedside venoarterial extracorporeal membrane
      oxygenation (ECMO) permitted time to physically  remove the obstructing tumor and
      reestablish successful ventilation and liberation from ventilatory support. We
      review several other reported cases of emergency ECMO to resuscitate patients
      with acute airway obstruction.

PMID- 22472503
TI  - Too many ventilator modes!

PMID- 22472504
TI  - Manual ventilation during resuscitation: does device matter?

PMID- 22472505
TI  - An ounce of prevention is worth a pound of cure.

PMID- 22472506
TI  - Head of bed elevation and ventilator-associated pneumonia.

PMID- 22472507
TI  - Infant feeding practices at routine PMTCT sites, South Africa: results of a
      prospective observational study amongst HIV exposed and unexposed infants - birth
      to 9 months.
AB  - BACKGROUND: We sought to investigate infant feeding practices amongst HIV
      positive and -negative mothers (0-9 months postpartum) and describe the
      association between infant feeding practices and HIV-free survival. METHODS:
      Infant feeding data from a prospective observational cohort study conducted at
      three (of 18) purposively-selected routine South African PMTCT sites, 2002-2003,
      were analysed. Infant feeding data (previous 4 days) were gathered during home
      visits at 3, 5, 7, 9, 12, 16, 20, 24, 28, 32 and 36 weeks postpartum. Four
      feeding groups were of interest, namely exclusive breastfeeding, mixed
      breastfeeding, exclusive formula feeding and mixed formula feeding. Cox
      proportional hazards models were fitted to investigate associations between
      feeding practices (0-12 weeks) and infant HIV-free survival. RESULTS: Six hundred
      and sixty five HIV-positive and 218 HIV-negative women were recruited antenatally
      and followed-up until 36 weeks postpartum. Amongst mothers who breastfed between
      3 weeks and 6 months postpartum, significantly more HIV-positive mothers
      practiced exclusive breastfeeding compared with HIV-negative: at 3 weeks 130
      (42%) versus 33 (17%) (p < 0.01); this dropped to 17 (11%) versus 1 (0.7%) by
      four months postpartum. Amongst mothers practicing mixed breastfeeding between 3
      weeks and 6 months postpartum, significantly more HIV-negative mothers used
      commercially available breast milk substitutes (p < 0.02) and use of these peaked
      between 9 and 12 weeks. The probability of postnatal HIV or death was lowest
      amongst infants living in the best resourced site who avoided breastfeeding, and
      highest amongst infants living in the rural site who stopped breastfeeding early
      (mean and standard deviations: 10.7% +/- 3% versus 46% +/- 11%). CONCLUSIONS:
      Although feeding practices were poor amongst HIV-positive and -negative mothers,
      HIV-positive mothers undertake safer infant feeding practices, possibly due to
      counseling provided through the routine PMTCT programme. The data on differences
      in infant outcome by feeding practice and site validate the WHO 2009
      recommendations that site differences should guide feeding practices amongst HIV
      positive mothers. Strong interventions are needed to promote exclusive
      breastfeeding (to 6 months) with continued breastfeeding thereafter amongst HIV
      negative motherswho are still the majority of mothers even in high HIV prevalence
      setting like South Africa.

PMID- 22472508
TI  - Overcoming castration resistance in prostate cancer.
AB  - PURPOSE OF REVIEW: Recent advances in our understanding of the androgen axis
      signaling pathway have led to the development of therapeutic strategies to
      overcome the state of 'castration resistance' in prostate cancer. In this review,
      we examine the mechanisms of castration resistance, as well as recently reported
      and ongoing clinical studies, which will further identify therapeutic
      opportunities for novel therapeutics targeting the androgen-signaling axis in
      advanced prostate cancer. RECENT FINDINGS: As evidenced by recently reported
      positive phase III clinical trials, secondary hormonal agents such as abiraterone
      and MDV3100 may still be very effective in the treatment of castration-resistant
      prostate cancer, even after the use of docetaxel chemotherapy. SUMMARY: Novel
      agents targeting this pathway have demonstrated a proof of principle that
      overcoming castration resistance is possible, leading to significant changes in
      the landscape of treatment in this disease. The optimal combination, sequence,
      and pattern of use in these novel therapies will be the focus of clinical
      research in the near future.

PMID- 22472509
TI  - Novel agents for the management of castration-resistant prostate cancer.
AB  - PURPOSE OF REVIEW: Over the past 2 years, four new treatments have entered the
      treatment armamentarium for patients with castration-resistant prostate cancer
      (CRPC). Although these novel agents differ in their mechanism of action, they all
      face the same challenges: patient selection, timing of therapy and the
      cost/benefit of their use. In this review, we will discuss their development and
      implications when selecting treatment options for CRPC patients. RECENT FINDINGS:
      Over the past few years, a better understanding of the biology of CRPC has
      allowed us to develop rational therapies that have resulted in an improvement in
      the outcome of prostate cancer patients. Immunotherapy has entered the field and
      despite its limitations and challenges is here to stay. A better understanding of
      the long-term complications of androgen deprivation has changed the initial
      approach to most patients with advanced disease, and bone health has become a
      major focus in their management. Understanding the importance of the androgen
      receptor and other ligands has led to a dramatic paradigm shift in the treatment
      of patients with metastatic disease in which the androgen receptor becomes a
      central therapeutic target in the disease. Specific adrenal inhibitors and
      engineered super androgen receptor inhibitors have become the most promising
      agents in the disease. Similarly, chemotherapy has demonstrated clinical benefit
      and is now a standard of care in docetaxel-refractory patients. SUMMARY: The
      management of CRPC patients continues to evolve. Novel treatments recently
      approved by the US Food and Drug Administration have significantly impacted the
      outcome of CRPC. With the economic impact of their use, selecting the right
      patient, defining the appropriate timing and sequence of therapy have become
      critical facts that need to be followed when defining the contemporary treatment
      options for men with CRPC.

PMID- 22472510
TI  - Cancer overdiagnosis and overtreatment.
AB  - PURPOSE OF REVIEW: Overdiagnosis has become a major problem in medicine in
      general and cancer in particular. This is a summary of this problem. RECENT
      FINDINGS: Because of earlier detection, the nature of cancer has changed, from a
      disease usually diagnosed at a late and incurable stage to a heterogeneous
      condition that varies from clinically insignificant to rapidly aggressive.
      Screening programs for cancer have resulted in a dramatic increase in the
      diagnosis of clinically insignificant disease, balanced by improved survival and
      mortality because of significant cancers being diagnosed at a more curable stage.
      Overdiagnosis requires the presence of microfocal disease and a screening test to
      identify this. This exists for breast, prostate, and thyroid cancers, and to a
      lesser degree for renal and lung cancer. The problem of cancer overdiagnosis and
      overtreatment is complex, with numerous causes and many trade-offs. It is
      particularly important in prostate cancer, but is a major issue in many other
      cancer sites. Screening for prostate cancer appears, based on the best data from
      randomized trials, to significantly reduce cancer mortality. SUMMARY: Reducing
      overtreatment in patients diagnosed with indolent disease is critical to the
      success of screening.

PMID- 22472511
TI  - The role of 5-alpha-reductase inhibitors in active surveillance.
AB  - PURPOSE OF REVIEW: Active surveillance is now considered one of the preferred
      treatments for men with favorable risk prostate cancer (PCa). Unfortunately, 30
      50% of men choosing active surveillance will progress and require therapy. In
      this context, we will present recent data on the efficacy of 5-alpha-reductase
      inhibitors (5-ARIs) in secondary prevention among men with low-risk PCa choosing
      active surveillance. RECENT FINDINGS: Two recent studies including a multicenter
      randomized controlled study demonstrate that 5-ARI may reduce the rate of
      clinical progression in low-risk PCa. SUMMARY: 5-ARIs may play an important role
      in secondary prevention in low-risk PCa. These results should be interpreted with
      caution in view of the recent US Food and Drug Administration recommendation
      against PCa chemoprevention labeling for 5-ARIs.

PMID- 22472512
TI  - Adhesion forces between AFM tips and superficial dentin surfaces.
AB  - In this work, we study the adhesion forces between atomic force microscopy (AFM)
      tips and superficial dentin etched with phosphoric acid. Initially, we
      quantitatively analyze the effect of acid etching on the surface heterogeneity
      and the surface roughness, two parameters that play a key role in the adhesion
      phenomenon. From a statistical study of the force-distance curves, we determine
      the average adhesion forces on the processed substrates. Our results show that
      the average adhesion forces, measured in water, increase linearly with the acid
      exposure time. The highest values of such forces are ascribed to the high density
      of collagen fibers on the etched surfaces. The individual contribution of exposed
      collagen fibrils to the adhesion force is highlighted. We also discuss in this
      paper the influence of the environmental medium (water/air) in the adhesion
      measurements. We show that the weak forces involved require working in the
      aqueous medium.

PMID- 22472513
TI  - Cationic ester-containing gemini surfactants: determination of aggregation
      numbers by time-resolved fluorescence quenching.
AB  - The micellar aggregation number of a series of ester-containing gemini
      surfactants has been determined with steady state and with time-resolved
      fluorescence quenching. The latter method gave values of aggregation number about
      twice those obtained with the former method. It was found that the length of the
      spacer was the most important factor affecting the aggregation number. The length
      and the nature of the surfactant alkyl chains were of less importance in spite of
      the fact that the length of the alkyl chains strongly affects the solution
      properties of the unimers.

PMID- 22472514
TI  - Developmental nephrotoxicity of aristolochic acid in a zebrafish model.
AB  - Aristolochic acid (AA) is a component of Aristolochia plant extracts which is
      used as a treatment for different pathologies and their toxicological effects
      have not been sufficiently studied. The aim of this study was to evaluate AA
      induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in
      AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic
      pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The
      percentages of embryos with malformed kidney phenotypes increased as the exposure
      dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly
      reduced glomerular filtration rates (GFRs) in comparison with mock-control
      littermates (mock-control: 100+/-2.24% vs. 10 ppm AA treatment for 3-5h: 71.48+/
      18.84%~39.41+/-15.88%), indicating that AA treatment not only caused
      morphological kidney changes but also induced renal failure. In addition to
      kidney malformations, AA-treated zebrafish embryos also exhibited deformed
      hearts, swollen pericardiums, impaired blood circulation and the accumulation(s)
      of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and
      wt1b as riboprobes indicated that the kidney is more sensitive than the heart to
      AA damage. Real-time PCR showed that AA can up-regulate the expression of
      proinflammatory genes like TNFalpha, cox2 and mpo. These results support the
      following conclusions: (1) AA-induced renal failure is mediated by inflammation,
      which causes circulation dysfunction followed by serious heart malformation; and
      (2) the kidney is more sensitive than the heart to AA injury.

PMID- 22472515
TI  - A randomized clinical trial of anticaries therapies targeted according to risk
      assessment (caries management by risk assessment).
AB  - This randomized parallel group clinical trial assessed whether combined
      antibacterial and fluoride therapy benefits the balance between caries
      pathological and protective factors. Eligible, enrolled adults (n = 231), with 1
      7 baseline cavitated teeth, attending a dental school clinic were randomly
      assigned to a control or intervention group. Salivary mutans streptococci (MS),
      lactobacilli (LB), fluoride (F) level, and resulting caries risk status (low or
      high) assays were determined at baseline and every 6 months. After baseline, all
      cavitated teeth were restored. An examiner masked to group conducted caries exams
      at baseline and 2 years after completing restorations. The intervention group
      used fluoride dentifrice (1,100 ppm F as NaF), 0.12% chlorhexidine gluconate
      rinse based upon bacterial challenge (MS and LB), and 0.05% NaF rinse based upon
      salivary F. For the primary outcome, mean caries increment, no statistically
      significant difference was observed (24% difference between control and
      intervention groups, p = 0.101). However, the supplemental adjusted zero-inflated
      Poisson caries increment (change in DMFS) model showed the intervention group had
      a statistically significantly 24% lower mean than the control group (p = 0.020).
      Overall, caries risk reduced significantly in intervention versus control over 2
      years (baseline adjusted generalized linear mixed models odds ratio, aOR = 3.45;
      95% CI: 1.67, 7.13). Change in MS bacterial challenge differed significantly
      between groups (aOR = 6.70; 95% CI: 2.96, 15.13) but not for LB or F. Targeted
      antibacterial and fluoride therapy based on salivary microbial and fluoride
      levels favorably altered the balance between pathological and protective caries
      risk factors.

PMID- 22472516
TI  - Over-expression of AtPAP2 in Camelina sativa leads to faster plant growth and
      higher seed yield.
AB  - BACKGROUND: Lipids extracted from seeds of Camelina sativa have been successfully
      used as a reliable source of aviation biofuels. This biofuel is environmentally
      friendly because the drought resistance, frost tolerance and low fertilizer
      requirement of Camelina sativa allow it to grow on marginal lands. Improving the
      species growth and seed yield by genetic engineering is therefore a target for
      the biofuels industry. In Arabidopsis, overexpression of purple acid phosphatase
      2 encoded by Arabidopsis (AtPAP2) promotes plant growth by modulating carbon
      metabolism. Overexpression lines bolt earlier and produce 50% more seeds per
      plant than wild type. In this study, we explored the effects of overexpressing
      AtPAP2 in Camelina sativa. RESULTS: Under controlled environmental conditions,
      overexpression of AtPAP2 in Camelina sativa resulted in longer hypocotyls,
      earlier flowering, faster growth rate, higher photosynthetic rate and stomatal
      conductance, increased seed yield and seed size in comparison with the wild-type
      line and null-lines. Similar to transgenic Arabidopsis, activity of sucrose
      phosphate synthase in leaves of transgenic Camelina was also significantly up
      regulated. Sucrose produced in photosynthetic tissues supplies the building
      blocks for cellulose, starch and lipids for growth and fuel for anabolic
      metabolism. Changes in carbon flow and sink/source activities in transgenic lines
      may affect floral, architectural, and reproductive traits of plants. CONCLUSIONS:
      Lipids extracted from the seeds of Camelina sativa have been used as a major
      constituent of aviation biofuels. The improved growth rate and seed yield of
      transgenic Camelina under controlled environmental conditions have the potential
      to boost oil yield on an area basis in field conditions and thus make Camelina
      based biofuels more environmentally friendly and economically attractive.

PMID- 22472517
TI  - Hospitalised and fatal head injuries in Viti Levu, Fiji: findings from an island
      wide trauma registry (TRIP 4).
AB  - BACKGROUND: Globally, head injury is a substantial cause of mortality and
      morbidity. A disproportionately greater burden is borne by low- and middle-income
      countries. The incidence and characteristics of fatal and hospitalised head
      injuries in Fiji are unknown. METHODS: Using prospective data from the Fiji
      Injury Surveillance in Hospital system, the epidemiology of fatal and
      hospitalised head injuries was investigated (2004-2005). RESULTS: In total, 226
      hospital admissions and 50 fatalities (66% died prior to admission) with a
      principal diagnosis of head injury were identified (crude annual rates of 34.7
      and 7.7/100,000, respectively). Males were more likely to die and be hospitalised
      as a result of head injury than females. The highest fatality rate was among
      those in the 30-44-year age group. Road traffic crashes were the leading causes
      of injuries resulting in death (70%), followed by 'hit by person or object' and
      falls (14% each). Among people admitted to hospital, road traffic crashes (34.5%)
      and falls (33.2%) were the leading causes of injury. The leading cause of head
      injuries in children was falls, in 15-29-year-olds road traffic crashes, and in
      adults aged 30-44 years or 45 years and older 'hit by person or object'. Among
      the two major ethnic groups, Fijians had higher rates of falls and 'hit by person
      or object' and Indians higher rates for road traffic crashes. There were no
      statistically significant differences between the overall rates of head injuries
      or the fatal and non-fatal rates among Fijians or Indians by gender following age
      standardisation to the total Fijian national population. CONCLUSION: Despite
      underestimating the overall burden, this study identified head injury to be a
      major cause of death and hospitalisation in Fiji. The predominance of males and
      road traffic-related injuries is consistent with studies on head injuries
      conducted in other low- and middle-income countries. The high fatality rate among
      those aged 30-44 years in this study has not been noted previously. The high case
      fatality rate prior to admission to the hospital requires urgent attention.

PMID- 22472518
TI  - An unusual wide QRS complex tachycardia: what is the mechanism?

PMID- 22472519
TI  - Obstructive sleep apnea, obesity, and atrial fibrillation--what is the
      mechanistic link?

PMID- 22472520
TI  - The influence of varying energy settings on efficacy and safety of endoscopic
      pulmonary vein isolation.
AB  - BACKGROUND: The optimal energy setting for endoscopic pulmonary vein (PV)
      isolation (PVI) has not yet been determined. OBJECTIVE: To assess the influence
      of varying energy settings on the efficacy and safety of endoscopic PVI. METHODS:
      In the current prospective study, 30 patients with paroxysmal atrial fibrillation
      were consented for PVI using the endoscopic ablation system. Ablation was
      performed by using 5.5 and 7.0 W (group A), 7.0 and 8.5 W (group B), and 8.5 and
      10.0 W (group C) along the posterior and anterior portion of each PV,
      respectively. Intraluminal esophageal temperature was measured via a temperature
      probe with a cutoff of 38.5 degrees C. Endoscopy was performed 2 days
      postablation. RESULTS: After the completion of the initial circular lesion set,
      acute PVI was achieved in 25 of the 36 (69%) PVs in group A, in 29 of the 40
      (73%) PVs in group B, and in 36 of the 40 (90%) PVs in group C, respectively. The
      rate of acute PVI was significantly higher in group C than in group A (P = .025)
      and group B (P = .045); there was no difference when comparing group A and group
      B (P = .77). Esophageal thermal lesions were detected in 0 of the 10 patients in
      group A, in 1 of the 10 (10%) patients in group B, and in 1 of the 10 (10%)
      patients in group C. Mean procedure and fluoroscopy times were 219 +/-42 and 30
      +/- 10, 239 +/- 61 and 38 +/- 14, and 207 +/- 31 and 28 +/- 8 minutes for group
      A, B, and C, respectively. CONCLUSIONS: The use of higher energy settings
      increases the efficacy of acute endoscopic ablation system-based PVI without
      comprising safety. Further investigation is mandatory before final conclusions
      can be drawn.

PMID- 22472521
TI  - The predictive capacity of personal genome sequencing.
AB  - New DNA sequencing methods will soon make it possible to identify all germline
      variants in any individual at a reasonable cost. However, the ability of whole
      genome sequencing to predict predisposition to common diseases in the general
      population is unknown. To estimate this predictive capacity, we use the concept
      of a "genometype." A specific genometype represents the genomes in the population
      conferring a specific level of genetic risk for a specified disease. Using this
      concept, we estimated the maximum capacity of whole-genome sequencing to identify
      individuals at clinically significant risk for 24 different diseases. Our
      estimates were derived from the analysis of large numbers of monozygotic twin
      pairs; twins of a pair share the same genometype and therefore identical genetic
      risk factors. Our analyses indicate that (i) for 23 of the 24 diseases, most of
      the individuals will receive negative test results; (ii) these negative test
      results will, in general, not be very informative, because the risk of developing
      19 of the 24 diseases in those who test negative will still be, at minimum, 50 to
      80% of that in the general population; and (iii) on the positive side, in the
      best-case scenario, more than 90% of tested individuals might be alerted to a
      clinically significant predisposition to at least one disease. These results have
      important implications for the valuation of genetic testing by industry, health
      insurance companies, public policy-makers, and consumers.

PMID- 22472522
TI  - A comparison of the autonomy over tobacco scale and the Fagerstrom test for
      nicotine dependence.
AB  - The autonomy over tobacco scale (AUTOS) is a 12-item theory-based instrument used
      to measure tobacco dependence in smokers. It provides separate measures of three
      factors that make smoking cessation more difficult: withdrawal symptoms,
      psychological dependence, and cue-induced urges to use tobacco. We compared the
      internal reliability and concurrent validity of the AUTOS to those of the
      Fagerstrom test for nicotine dependence (FTND). Adult current smokers (n=422; 62%
      female; 86.8% white; mean age 33.3 years, SD=13.7; 57% daily smokers) completed
      an anonymous web-based survey that included the AUTOS, the FTND and 11 smoking
      related behavioral measures. Cronbach's alpha was .94 for the AUTOS and alpha>.75
      for each of the 3 subscales; alpha=.73 for the FTND. The AUTOS and its subscales
      correlated with all measures of concurrent validity (r=.70 between AUTOS & FTND).
      The AUTOS correlated better than the FTND with the Hooked on Nicotine Checklist,
      the longest period of abstinence, latency to wanting, percentage of time a person
      smokes because of momentary need, pleasure from smoking, days smoked per month,
      and concern about deprivation. The measures showed similar correlations with the
      latencies to craving and needing. The FTND correlated better with the duration of
      smoking and cigarettes smoked per day. Based on these results and those from
      prior studies, we conclude that the AUTOS offers researchers a valid and highly
      reliable, theory-based measure that is more versatile in its applications than
      the FTND.

PMID- 22472523
TI  - Enhanced motivational interviewing versus brief advice for adolescent smoking
      cessation: results from a randomized clinical trial.
AB  - BACKGROUND: Motivational interviewing (MI) is widely used for adolescent smoking
      cessation but empirical support for this approach is mixed. METHODS: Adolescent
      cigarette smokers 14-18 years old (N=162) were recruited from medical, school,
      and community settings and randomly assigned to enhanced MI or brief advice (BA)
      for smoking cessation. MI comprised an in-person individual session, a telephone
      booster session one week later, and a brief telephone-based parent intervention.
      BA consisted of standardized brief advice to quit smoking. Assessments occurred
      at baseline, post-treatment and at 1-, 3-, and 6-month follow ups. RESULTS:
      Biochemically-confirmed 7-day point prevalence abstinence rates were low (e.g.,
      4.5% for MI; 1.4% for BA at 1 month) and did not differ significantly by group at
      any follow up. Only those in MI reported significant decreases in cigarettes
      smoked per day (CPD) from baseline to 1 month. At 3 and 6 months, smokers in both
      groups reported significantly reduced CPD with no differences between groups. MI
      reduced perceived norms regarding peer and adult smoking rates, while BA had no
      effect on normative perceptions. No group differences emerged for self-reported
      motivation or self-efficacy to quit smoking. CONCLUSIONS: Findings support the
      efficacy of MI for addressing normative misperceptions regarding peer and adult
      smoking and for modestly reducing CPD in the short-term; however, these effects
      did not translate to greater smoking abstinence. MI may have more promise as a
      prelude to more intensive smoking intervention with adolescents than as a stand
      alone intervention.

PMID- 22472524
TI  - Drinking motives as mediators of the impulsivity-substance use relation: pathways
      for negative urgency, lack of premeditation, and sensation seeking.
AB  - Trait impulsivity is a reliable, robust predictor of risky, problematic alcohol
      use. Mounting evidence supports a multidimensional model of impulsivity, whereby
      several distinct traits serve as personality pathways to rash action. Different
      impulsivity-related traits may predispose individuals to drink for different
      reasons (e.g., to enhance pleasure, to cope with distress) and these different
      motives may, in turn, influence drinking behavior. Previous findings support such
      a mediational model for two well-studied traits: sensation seeking and lack of
      premeditation. This study addresses other impulsivity-related traits, including
      negative urgency. College students (N=432) completed questionnaires assessing
      personality, drinking motives, and multiple indicators of problematic drinking.
      Negative urgency, sensation seeking, and lack of premeditation were all
      significantly related to problematic drinking. When drinking motives were
      included in the model, direct effects for sensation seeking and lack of
      premeditation remained significant, and indirect effects of sensation seeking and
      lack of premeditation on problematic drinking were observed through enhancement
      motives. A distinct pathway was observed for negative urgency. Negative urgency
      bore a significant total effect on problematic drinking through both coping and
      enhancement motives. This study highlights unique motivational pathways through
      which different impulsive traits may operate, suggesting that interventions aimed
      at preventing or reducing problematic drinking should be tailored to individuals'
      personalities. For instance, individuals high in negative urgency may benefit
      from learning healthier strategies for coping with distress.

PMID- 22472525
TI  - Model-oriented review and multi-body simulation of the ossicular chain of the
      human middle ear.
AB  - The ossicular chain of the human middle ear has a key role in sound conduction
      since it transfers vibrations from the tympanic membrane to the cochlea,
      connecting the outer and the inner part of the hearing organ. This study reports
      firstly a description of the main anatomical features of the middle ear to
      introduce a detailed survey of its biomechanics, focused on model development,
      with a collection of geometric, inertial and mechanical/material parameters. The
      joint issues are particularly discussed from the perspective of developing a
      model of the middle ear both explanatory and predictive. Such a survey underlines
      the remarkable dispersion of data, due also to the lack of a standardization of
      the experimental techniques and conditions. Subsequently, a 3D multi-body model
      of the ossicular chain and other structures of the middle ear is described. Such
      an approach is justified as the ossicles were proven to behave as rigid bodies in
      the human hearing range and was preferred to the more widely used finite element
      one as it simplifies the model development and improves joint modeling. The
      displacement of the umbo (a reference point of the tympanic membrane) in the 0.3
      6kHz frequency range was defined as input of the model, while the stapes
      footplate displacement as output. A parameter identification procedure was used
      to find parameter values for reproducing experimental and numerical reference
      curves taken from the literature. This simple model might represent a valid
      alternative to more complex models and might provide a useful tool to simulate
      pathological/post-surgical/post-traumatic conditions and evaluate ossicular
      replacement prostheses.

PMID- 22472526
TI  - A mechanical jig for measuring ankle supination and pronation torque in vitro and
      in vivo.
AB  - This study presents the design of a mechanical jig for evaluating the ankle joint
      torque on both cadaver and human ankles. Previous study showed that ankle sprain
      motion was a combination of plantarflexion and inversion. The device allows
      measurement of ankle supination and pronation torque with one simple axis in a
      single step motion. More importantly, the ankle orientation allows rotation
      starting from an anatomical position. Six cadaveric specimens and six human
      subjects were tested with simulated and voluntary rotation respectively. The
      presented mechanical jig makes possible the determination of supination torque
      for studying ankle sprain injury and the estimation of pronation torque for
      examining peroneal muscle response.

PMID- 22472527
TI  - Amperometric sulfide detection using Coprinus cinereus peroxidase immobilized on
      screen printed electrode in an enzyme inhibition based biosensor.
AB  - In the present work, an amperometric inhibition biosensor for the determination
      of sulfide has been fabricated by immobilizing Coprinus cinereus peroxidase (CIP)
      on the surface of screen printed electrode (SPE). Chitosan/acrylamide was applied
      for immobilization of peroxidase on the working electrode. The amperometric
      measurement was performed at an applied potential of -150 mV versus Ag/AgCl with
      a scan rate of 100 mV in the presence of hydroquinone as electron mediator and
      0.1M phosphate buffer solution of pH 6.5. The variables influencing the
      performance of sensor including the amount of substrate, mediator concentration
      and electrolyte pH were optimized. The determination of sulfide can be achieved
      in a linear range of 1.09-16.3 MUM with a detection limit of 0.3 MUM. Developed
      sensor showed quicker response to sulfide compared to the previous developed
      sulfide biosensors. Common anions and cations in environmental water did not
      interfere with sulfide detection by the developed biosensor. Cyanide interference
      on the enzyme inhibition caused 43.25% error in the calibration assay which is
      less than the amounts reported by previous studies. Because of high sensitivity
      and the low-cost of SPE, this inhibition biosensor can be successfully used for
      analysis of environmental water samples.

PMID- 22472528
TI  - The application of Au nanoclusters in the fluorescence imaging of human serum
      proteins after native PAGE: enhancing detection by low-temperature plasma
      treatment.
AB  - Proteins in human serum are increasingly being studied for their roles in a wide
      variety of biochemical interactions. To improve the sensitivity of the detection
      of human serum proteins after native polyacrylamide gel electrophoresis (PAGE),
      we have developed a fluorescence imaging detection technique for the detection.
      BSA (bovine serum albumin)-stabilized Au nanoclusters (NCs) were applied as
      fluorescent probes for imaging, and low-temperature plasma (LTP) treatment of the
      Au NCs was introduced to enhance the fluorescence imaging. Here, a series of
      optimization experiments (e.g. those to optimize for pH) were conducted for
      protein detection after 1-DE and 2-DE, and several types of discharge gases (He,
      O(2), and N(2)) were selected for the LTP treatment. The possible mechanism of
      interaction between the proteins and the Au NCs was demonstrated by an isothermal
      titration calorimetry experiment. Using the present method, a sensitivity of 7-14
      times higher than that of traditional staining detection methods was observed in
      the oxygen LTP-treated Au NCs fluorescence images, and some relatively low
      abundance proteins (identified by the MS/MS technique) were easily detected. In
      addition, this fluorescence imaging method was applied to distinguish between the
      serum samples of patients with liver diseases and those of healthy people. Thus,
      this fluorescence imaging method is suitable for the highly sensitive detection
      of various serum proteins, and it shows potential capabilities for clinical
      diagnosis.

PMID- 22472529
TI  - A strategy for high-throughput screening of ligands suitable for molecular
      imprinting of proteins.
AB  - For facilitating the identification of appropriate functionalities that may serve
      as a binding motif of functional monomers, a selection strategy based on high
      throughput screening of the binding properties of readily available sorbent
      materials has been developed. Thereby, the affinity of such ligands to the
      protein of interest may be rapidly determined. From these studies, it is
      anticipated that ligand functionalities will be derived, which may lead to
      advanced selection and design of dedicated functional monomers suitable for
      decorating the surface of a scavenger material. Thus, specific binding of the
      target protein of interest should be enabled even in complex solutions such as
      e.g., biotechnologically relevant cell lysates. In the present contribution, an
      automated screening method for studying ligand interactions of selected sorbent
      materials with pepsin - a protein of the protease family - was developed. Aqueous
      buffer solutions containing pepsin at known constant concentration were pipetted
      through an array of miniaturized chromatographic solid phase extraction (SPE)
      columns containing a variety of sorbent materials, and the eluted solutions were
      analyzed by UV/vis spectroscopy. The established screening protocol was validated
      against resin materials of known interaction with pepsin. Finally, the developed
      screening strategy was adapted for a robot system enabling high-throughput
      screening for a wide variety of sorbent materials and ligand functionalities in a
      fully automated approach. The obtained results clearly indicate that the
      established screening routine provides valuable data for characterizing resin
      immobilized ligands, and their affinity toward pepsin.

PMID- 22472530
TI  - Determination of glucose and uric acid with bienzyme colorimetry on microfluidic
      paper-based analysis devices.
AB  - In this work, we first employ a drying method combining with the bienzyme
      colorimetric detection of glucose and uric acid on microfluidic paper-based
      analysis devices (MUPADs). The channels of 3D MUPADs are also designed by us to
      get better results. The color results are recorded by both Gel Documentation
      systems and a common camera. By using Gel Documentation systems, the limits of
      detection (LOD) of glucose and uric acid are 3.81 * 10(-5)M and 4.31 * 10(-5)M,
      respectively one order of magnitude lower than that of the reported methods on
      MUPADs. By using a common camera, the limits of detection (LOD) of glucose and
      uric acid are 2.13 * 10(-4)M and 2.87 * 10(-4)M, respectively. Furthermore, the
      effects of detection conditions have been investigated and discussed
      comprehensively. Human serum samples are detected with satisfactory results,
      which are comparable with the clinical testing results. A low-cost, simple and
      rapid colorimetric method for the simultaneous detection of glucose and uric acid
      on the MUPADs has been developed with enhanced sensitivity.

PMID- 22472531
TI  - An acoustic glucose sensor.
AB  - In vivo glucose monitoring is required for tighter glycaemic control. This report
      describes a new approach to construct a miniature implantable device based on a
      magnetic acoustic resonance sensor (MARS). A ~ 600-800 nm thick glucose
      responsive poly(acrylamide-co-3-acrylamidophenylboronic acid) (poly(acrylamide-co
      3-APB)) film was polymerised on the quartz disc (12 mm in diameter and 0.25 mm
      thick) of the MARS. The swelling/shrinking of the polymer film induced by the
      glucose binding to the phenylboronate caused changes in the resonance amplitude
      of the quartz disc in the MARS. A linear relationship between the response of the
      MARS and the glucose concentration in the range ~ 0-15 mM was observed, with the
      optimum response of the MARS sensor being obtained when the polymer films
      contained ~ 20 mol% 3-APB. The MARS glucose sensor also functioned under flow
      conditions (9 MUl/min) with a response almost identical to the sensor under
      static or non-flow conditions. The results suggest that the MARS could offer a
      promising strategy for developing a small subcutaneously implanted continuous
      glucose monitor.

PMID- 22472532
TI  - Brain disease leading to mental illness: a concept initiated by the discovery of
      general paralysis of the insane.
AB  - In the early 19th century the prevailing alienist (psychiatrists') view was that
      organic lesions did not cause madness. The history of general paralysis of the
      insane (GPI) rests on four early publications which changed this concept:
      Haslam's Observations on insanity, Bayle's Recherches sur l'arachnitis chronique,
      Calmeil's De la paralysie consideree chez les alienes, and Esmarch and Jessen's
      Syphilis und Geistesstorung. Haslam's account is unconvincing, but Bayle's report
      linking mental alienation with organic brain disease was a polemic that opposed
      established teachings. Calmeil and Delaye emphasised clinicopathological
      correlation and stressed the importance of white matter disease in causing
      dementia. GPI was to prove a crucial starting point in which the causes of mental
      illness were slowly transformed from psychogenic disturbances of mind and spirits
      to organically determined diseases.

PMID- 22472533
TI  - Enzyme activities in the oral fluids of patients suffering from bulimia: a
      controlled clinical trial.
AB  - Patients with bulimia nervosa are at high risk for dental erosion. However, not
      all bulimic patients suffer from erosion, irrespective of the severity of their
      eating disorder. It is often speculated that differences in the saliva are
      important, however, little is known about salivary parameters in bulimic
      patients, particularly directly after vomiting. The aim of the clinical trial was
      to compare different salivary parameters of subjects suffering from bulimia with
      those of healthy controls. Twenty-eight subjects participated (14 patients with
      bulimia nervosa, 7 of them with erosion; 14 matched healthy controls). Resting
      and stimulated saliva of all participants was analysed as well as saliva
      collected from bulimic patients directly and 30 min after vomiting. Parameters
      under investigation were flow rate, pH, buffering capacity and the enzyme
      activities of proteases in general, collagenase, pepsin, trypsin, amylase,
      peroxidase, and lysozyme. Regarding flow rate, pH and buffering capacity only
      small differences were found between groups; buffering capacity directly after
      vomiting was significantly lower in bulimic subjects with erosion than in
      subjects without erosion. Differences in enzymatic activities were more
      pronounced. Activities of proteases, collagenase and pepsin in resting and
      proteases in stimulated saliva were significantly higher in bulimic participants
      with erosion than in controls. Peroxidase activity was significantly decreased by
      regular vomiting. Proteolytic enzymes seem to be relevant for the initiation and
      progression of dental erosion directly after vomiting, maybe by both hydrolysis
      of demineralized dentine structures as well as modulation of the pellicle layer.

PMID- 22472534
TI  - Treatment of nephroblastoma with polycythaemia by nephrectomy in a rabbit.

PMID- 22472535
TI  - Panic in free-range laying hens.

PMID- 22472536
TI  - Medium term endoscopic assessment of the surgical outcome following laryngeal
      saccule resection in brachycephalic dogs.
AB  - Laryngeal saccule eversion has been widely reported as an important component of
      brachycephalic airway obstructive syndrome (BAOS). The authors hypothesised that
      saccules affected by acute histological changes in patients showing marked
      improvement following palate and nares surgery might spontaneously return to
      normal; moreover, spontaneous resolution of the eversion in patients with
      fibrotic saccules and/or without clinical improvement following BAOS surgery
      might be impossible and, on the contrary, the persistence of turbulent airflow
      and associated ongoing inflammation might lead to aberrant tissue proliferation
      after resection. In order to demonstrate our hypotheses, the authors decided to
      perform a unilateral sacculectomy and to postpone and assess the need for the
      execution of the contralateral saccule resection according to the findings of a
      second-look laryngoscopy. Ten dogs were enrolled. None of the saccules left in
      situ underwent spontaneous resolution of the eversion. In one dog, after
      sacculectomy, proliferation of a soft tissue lesion endoscopically similar to a
      newly formed saccule occurred. The results of the present study suggest that
      spontaneous resolution of saccule eversion is uncommon, even after the correction
      of the primary abnormalities (palate, nares). Resection of the saccules can
      relieve ventral rima glottidis obstruction; however, secondary intention healing
      might occasionally result in the recurrence of the obstruction.

PMID- 22472537
TI  - Haptoglobin concentration in galgos and greyhounds.

PMID- 22472538
TI  - Retrospective study of 155 cases of prolapse of the nictitating membrane gland in
      dogs.
AB  - A retrospective study of 155 cases (114 dogs). The breed, sex and age at the time
      of the first and opposite onset of nictitans gland prolapse were recorded. Long
      term follow-up with a minimum of one-year duration was performed by telephone
      conversations. One hundred and fourteen dogs representing 155 nictitans gland
      prolapses were included. 75.4 per cent of the first prolapse occur before one
      year of age. Unilateral nictitans gland prolapse was observed in 64 per cent of
      cases. When the condition was bilateral, it occurred simultaneously in 41.4 per
      cent. When it was bilateral but not simultaneous (24/41), the opposite gland
      prolapse occurred within three months in 70.8 per cent of the cases. Five breeds
      were most commonly affected by the bilateral condition: French bulldog, shar pei,
      great dane, English bulldog and cane corso.

PMID- 22472539
TI  - Fluoroquinolone susceptibility of Staphylococcus aureus strains isolated from
      commercial rabbit farms in Spain.

PMID- 22472540
TI  - Investigation of the role of mules as silent shedders of EHV-1 during an outbreak
      of EHV-1 myeloencephalopathy in California.

PMID- 22472541
TI  - Tying fallopian tubes to ovarian cancer risk.

PMID- 22472542
TI  - Unraveling genes, hormones, and breast cancer.

PMID- 22472544
TI  - Chemotherapy culture differences persist, but molecular insights foster change.

PMID- 22472545
TI  - Studies on how lifestyle factors may affect breast cancer risk and recurrence.

PMID- 22472546
TI  - CYP3A variation, premenopausal estrone levels, and breast cancer risk.
AB  - BACKGROUND: Epidemiological studies have provided strong evidence for a role of
      endogenous sex steroids in the etiology of breast cancer. Our aim was to identify
      common variants in genes involved in sex steroid synthesis or metabolism that are
      associated with hormone levels and the risk of breast cancer in premenopausal
      women. METHODS: We measured urinary levels of estrone glucuronide (E1G) using a
      protocol specifically developed to account for cyclic variation in hormone levels
      during the menstrual cycle in 729 healthy premenopausal women. We genotyped 642
      single-nucleotide polymorphisms (SNPs) in these women; a single SNP, rs10273424,
      was further tested for association with the risk of breast cancer using data from
      10 551 breast cancer case patients and 17 535 control subjects. All statistical
      tests were two-sided. RESULTS: rs10273424, which maps approximately 50 kb
      centromeric to the cytochrome P450 3A (CYP3A) gene cluster at chromosome 7q22.1,
      was associated with a 21.8% reduction in E1G levels (95% confidence interval [CI]
      = 27.8% to 15.3% reduction; P = 2.7 * 10(-9)) and a modest reduction in the risk
      of breast cancer in case patients who were diagnosed at or before age 50 years
      (odds ratio [OR] = 0.91, 95% CI = 0.83 to 0.99; P = .03) but not in those
      diagnosed after age 50 years (OR = 1.01, 95% CI = 0.93 to 1.10; P = .82).
      CONCLUSIONS: Genetic variation in noncoding sequences flanking the CYP3A locus
      contributes to variance in premenopausal E1G levels and is associated with the
      risk of breast cancer in younger patients. This association may have wider
      implications given that the most predominantly expressed CYP3A gene, CYP3A4, is
      responsible for metabolism of endogenous and exogenous hormones and hormonal
      agents used in the treatment of breast cancer.

PMID- 22472547
TI  - Increasing efforts to regulate computed tomography scans.

PMID- 22472549
TI  - Predicting outcomes of patients with intracranial meningiomas using molecular
      markers of hypoxia, vascularity, and proliferation.
AB  - BACKGROUND: The natural history of surgically treated intracranial meningiomas
      can be quite variable. Recurrence and patient outcome cannot currently be
      predicted with accuracy. OBJECTIVE: To explore the potential roles of tumor
      hypoxia-regulated biological markers, preoperative imaging, measures of
      proliferation, and angiogenesis in predicting patient outcome. METHODS: Tissue
      from 263 patients (average follow-up, 75 months) was examined for molecular
      markers hypoxia-inducible factor-1alpha (HIF-1alpha), carbonic anhydrase-IX (CA
      IX), and glucose transporter-1 (Glut-1); vascular endothelial growth factor
      (VEGF); proliferation (MIB-1); and microvascular density (MVD) (Factor VIII).
      Preoperative magnetic resonance images were also examined for tumor size and
      peritumoral brain edema (PTBE). RESULTS: VEGF, HIF-1alpha, CA-IX, and Glut-1 are
      positively correlated (P < .001-.005). PTBE was associated with higher grade (P =
      .03), larger tumors (P = .02), and log of MVD (P = .004). Progression-free
      survival (PFS) was associated with higher grade (P < .001), subtotal resection (P
      = .004), VEGF expression (P = .004), and log of MIB-labeling index (P < .001) on
      pairwise comparisons. Using multivariate analysis, PFS was associated with
      subtotal resection (HR 2.71, P = .027), higher grade (HR 6.29, P < .001), higher
      VEGF expression (HR 1.52, P = .038), and log of MIB-labeling index (HR 1.68, P =
      .005). Shorter overall survival was associated with subtotal resection (HR 3.23,
      P = .002), higher grade (HR 4.47, P < .001), higher expression of HIF-1alpha (HR
      1.56, P < .001) and Glut-1 (HR 1.39, P = .02), and log of MIB-labeling index (HR
      1.87, P < .001) when controlled for age. CONCLUSION: HIF, VEGF, and MIB-1 are
      significantly correlated with tumor recurrence. With further study, these
      molecular markers may be used to predict outcome for patients with intracranial
      meningiomas.

PMID- 22472550
TI  - Stereotactic radiotherapy for trigeminal schwannomas.
AB  - BACKGROUND: Data on radiotherapy for trigeminal schwannomas (TSs) and comparison
      of stereotactic radiosurgery (SRS) with fractionated stereotactic radiotherapy
      (FSRT) are limited. OBJECTIVE: We present a large retrospective review of our
      institutional experience treating TSs with SRS and FSRT. We also describe a flare
      phenomenon experienced by some patients. METHODS: The records of 23 consecutive
      TSs patients treated with radiotherapy between 1996 and 2011 were reviewed. We
      investigated radiographic response, tumor control, and toxicity. RESULTS: Ten
      patients underwent SRS and 13 underwent FSRT, with median clinical follow-up of
      32 months (range, 3-120 months). Tumor control at 5 and 10 years was 94% overall.
      Symptom control at 5 years was achieved in 48% of all patients, with
      nonsignificant improvement in more patients in the FSRT group than those in the
      SRS group (56% vs 40%, P = .37). Acute toxicity was higher in the FSRT group
      (38.5 vs 0%, P < .01), although lesions treated with FSRT were larger (mean, 9.5
      mL vs 4.8 mL, P < .01). A symptomatic flare phenomenon occurred in 2 patients
      (8.7% overall) during FSRT, involving transient cystic formation and dramatic
      size increase. One lesion regressed in size and 1 remained stable on follow-up.
      CONCLUSION: Tumor control rates for TSs are excellent with SRS and FSRT with
      minimal toxicity. This represents the first documented report of a flare
      phenomenon after FSRT for TS treatment. Flare risk after FSRT in previously
      resected large lesions should be discussed with patients before treatment, and
      prophylactic oral steroids may be considered.

PMID- 22472551
TI  - Multimodality treatment of conus medullaris arteriovenous malformations:  2
      decades of experience with combined endovascular and microsurgical treatments.
AB  - BACKGROUND: Conus medullaris arteriovenous malformations (AVMs) are rare,
      challenging spinal vascular lesions that cause progressive debilitating
      myeloradiculopathy. Only sporadic reports of conus AVMs have been published.
      OBJECTIVE: To better define the presentation, prognosis, and optimal treatment of
      these lesions, we present the first case series of conus AVMs, reflecting over 2
      decades of experience with a multimodality endovascular and surgical approach.
      METHODS: We retrospectively reviewed the charts of 16 patients with a conus AVM
      evaluated at our institution from 1989 to 2010. For each patient, the following
      clinical data were collected: age, sex, symptoms, angiographic findings, type of
      treatment, complications, degree of angiographic obliteration, recurrence at
      follow-up, and need for re-treatment. Ambulatory status, Frankel Grade, motor
      function, and bladder/bowel function were assessed before treatment, at
      discharge, and at last follow-up. RESULTS: All 16 patients were treated. Eight
      (50%) patients underwent embolization followed by microsurgical resection, and 8
      (50%) underwent microsurgical resection only. The rate of complete angiographic
      obliteration was 88%. At last follow-up (mean, 70 months), 43% of patients
      neurologically improved, 43% were stable, and 14% worsened in comparison with
      before treatment. During follow-up, 3 recurrences were detected, including the
      only 2 instances of long-term neurological decline. In the absence of recurrence,
      all patients ambulatory before treatment remained ambulatory at follow-up,
      whereas 75% of the initially nonambulatory patients regained the ability to walk.
      CONCLUSION: Although conus AVMs are challenging to treat, excellent long-term
      outcomes are possible with a multimodality approach. Recurrence is associated
      with long-term neurological decline and calls for close follow-up.

PMID- 22472552
TI  - The frontotemporal (pterional) approach:  an historical perspective.
AB  - The frontotemporal, so-called pterional, approach has evolved with the
      contribution of many neurosurgeons over the past century. It has stood the test
      of time and has been the most commonly used transcranial approach in
      neurosurgery. In its current form, drilling the sphenoid wing as far down as the
      superior orbital fissure with or without the removal of the anterior clinoid,
      thinning the orbital roof, and opening the Sylvian fissure and basal cisterns are
      the hallmarks of this approach. Tumoral and vascular lesions involving the
      sellar/parasellar area, anterior and anterolateral circle of Willis, middle
      cerebral artery, anterior brainstem, upper basilar artery, insula, basal ganglia,
      mesial temporal region, anterior cranial fossa, orbit, and optic nerve are within
      the reach of the frontotemporal approach. In this article, we review the origins,
      evolution, and modifications of the frontotemporal approach and update the
      discussion of some of the related derivative procedures.

PMID- 22472553
TI  - Risk factors for acute subdural hematoma from intracranial aneurysm rupture.
AB  - BACKGROUND: An acute subdural hematoma (aSDH) is a rare complication of
      aneurysmal subarachnoid hemorrhage (SAH) and is associated with poor clinical
      condition on admission and poor outcome. Risk factors for the development of an
      aSDH from aneurysmal rupture are unknown and may help our understanding of how an
      aSDH develops. OBJECTIVE: To identify risk factors for the development of an aSDH
      from intracranial aneurysm rupture. METHODS: Patients were selected from our
      prospectively collected single-center SAH database. From all 1757 patients
      fulfilling prespecified inclusion criteria, 63 had an aSDH. We assessed sex, age,
      smoking, hypertension, history of SAH, sentinel headache, location of the
      ruptured aneurysm, and intracerebral hemorrhage (ICH) as risk factors for an
      aSDH. Univariable and multivariable risk ratios with corresponding 95% confidence
      intervals (CIs) were calculated for characteristics with Poisson regression.
      RESULTS: Multivariable risk ratios were 1.021 (95% CI: 1.001-1.042) for each year
      increase in age, 2.3 (95% CI: 1.3-3.8) for posterior communicating artery
      aneurysms, 3.0 (95% CI: 1.5-6.0) for sentinel headache, and 5.2 (95% CI: 3.1-8.9)
      for ICH. None of the 95 patients (0%; 95% CI: 0%-3.8%) with a ruptured
      vertebrobasilar aneurysm had an aSDH, which was statistically significantly lower
      than at other sites (P = .02 for basilar aneurysm; P = .04 for vertebral
      aneurysm). None of the other studied characteristics had a statistically
      significant association with an aSDH. CONCLUSION: Increasing age, sentinel
      headache, ICH, and aneurysms at the posterior communicating artery are
      independent risk factors for an aSDH. Patients with a basilar or vertebral
      aneurysm have a low risk of an aSDH.

PMID- 22472554
TI  - Hemorrhage from arteriovenous malformations during pregnancy.
AB  - BACKGROUND: Previous hemorrhage, deep venous drainage, and deep location are
      established risk factors for arteriovenous malformation (AVM) hemorrhage.
      Although pregnancy is an assumed risk factor, there is a relative paucity of data
      to support this neurosurgical tenet. OBJECTIVE: To elucidate the hemorrhage rate
      of AVMs during pregnancy. METHODS: We reviewed the records of 54 women with an
      angiographic diagnosis of an AVM at our institution. Annual hemorrhage rates were
      calculated as the ratio of the number of bleeds to total number of patient-years
      of follow-up. Patient-years of follow-up were tallied assuming lesion presence
      from birth until AVM obliteration. The Cox proportional hazards model for
      hemorrhage with pregnancy as the time-dependent variable was used to calculate
      the hazard ratio. RESULTS: Five hemorrhages in 4 patients occurred over 62
      pregnancies, yielding a hemorrhage rate of 8.1% per pregnancy or 10.8% per year.
      Over the remaining 2461.3 patient-years of follow-up, only 28 hemorrhages
      occurred, yielding an annual hemorrhage rate of 1.1%. The hazard ratio for
      hemorrhage during pregnancy was 7.91 (P = 2.23 * 10(-4)), increasing to 18.12 (P
      = 7.31 * 10(-5)) when limiting the analysis to patient follow-up up to age 40.
      CONCLUSION: Because of the increased risk of hemorrhage from AVMs during
      pregnancy, we recommend intervention in women who desire to bear children,
      particularly if the AVM has bled. If the AVM is discovered during pregnancy, we
      recommend early intervention if it has ruptured; if it is unruptured, we
      recommend comprehensive counseling, weighing risks of intervention against
      continuation of pregnancy without intervention.

PMID- 22472555
TI  - Advanced technical skills are required for microsurgical clipping of posterior
      communicating artery aneurysms in the endovascular era.
AB  - BACKGROUND: Many neurosurgeons feel competent clipping posterior communicating
      artery (PCoA) aneurysms and include this lesion in their practice. However,
      endovascular therapy removes simple aneurysms that would have been easiest to
      clip with the best results. What remains are aneurysms with complex anatomy and
      technical challenges that are not well described. OBJECTIVE: A contemporary
      surgical series with PCoA aneurysms is reviewed to define the patients,
      microsurgical techniques, and outcomes in current practice. METHODS: A total of
      218 patients had 218 PCoA aneurysms that were treated microsurgically during an
      11-year period. Complexities influencing aneurysm management included (1)
      large/giant size; (2) fetal posterior cerebral artery; (3) previous coiling; (4)
      anterior clinoidectomy; (5) adherence of the anterior choroidal artery (AChA);
      (6) intraoperative aneurysm rupture; (7) complex clipping; and (8)
      atherosclerotic calcification. RESULTS: Simple PCoA aneurysms were encountered in
      113 patients (51.8%) and complex aneurysms in 105 (48.2%). Adherent AChA (13.8%)
      and intraoperative rupture (11.5%) were the most common complexities. Simple
      aneurysms had favorable outcomes in 86.6% of patients, whereas aneurysms with 1
      or multiple complexities had favorable outcomes in 78.2% and 75.0%, respectively.
      Intraoperative rupture (P < .01), large/giant size (P = .04), and complex
      clipping (P = .05) were associated with increased neurological worsening.
      CONCLUSION: Because endovascular therapy alters the surgical population,
      neurosurgeons should recalibrate their expectations with this once
      straightforward aneurysm. The current mix of PCoA aneurysms requires advanced
      techniques including clinoidectomy, AChA microdissection, complex clipping, and
      facility with intraoperative rupture. Microsurgery is recommended for recurrent
      aneurysms after coiling, complex branches, aneurysms causing oculomotor nerve
      palsy, multiple aneurysms, and patients with hematomas.

PMID- 22472556
TI  - Long-term results of enterprise stent-assisted coiling of cerebral aneurysms.
AB  - BACKGROUND: The Enterprise Vascular Reconstruction Device and Delivery System
      (Cordis; the Enterprise stent) was approved for use in conjunction with coiling
      of wide-necked aneurysms in 2007. No published long-term aneurysm occlusion or
      complication data exist for the Enterprise system. OBJECTIVE: We compiled data on
      consecutive patients treated with Enterprise stent-assisted coiling of aneurysms
      from 9 high-volume neurointerventional centers. METHODS: A 9 center registry was
      created to evaluate large volume data on the delayed safety and efficacy of the
      Enterprise stent system. Pooled data were compiled for consecutive patients
      undergoing Enterprise stent-assisted coiling at each institution prior to May
      2009. RESULTS: Two-hundred twenty-nine patients with 229 aneurysms, 32 of which
      were ruptured aneurysms, were included in the study. Mean clinical and
      angiographic follow-up was 619.6 +/- 26.4 days and 655.7 +/- 25.2 days,
      respectively. Mean aneurysm size was 9.2 +/- 0.4 mm. Fifty-nine percent of
      patients demonstrated 100% coil obliteration and 81% had 90% or higher occlusion
      at last follow-up angiography. A total of 19 patients (8.3%) underwent
      retreatment of their aneurysms during the follow-up period. Angiographic in-stent
      stenosis was seen in 3.4% and thromboembolic events occurred in 4.4%. Overall,
      90% of patients who underwent Enterprise-assisted coiling had a modified Rankin
      Scale score of 2 or less at last follow-up. A poor modified Rankin Scale score
      was strongly associated with rupture status (P < .001). CONCLUSION: Although this
      study is limited by its retrospective nature, the Enterprise stent system appears
      to be an effective, safe, and durable treatment for intracranial aneurysms when
      used in conjunction with coiling.

PMID- 22472557
TI  - Grafting the C5 root to the musculocutaneous nerve partially restores hand
      sensation in complete palsies of the brachial plexus.
AB  - BACKGROUND: In complete brachial plexus palsy, we have hypothesized that grafting
      to the musculocutaneous nerve should restore some hand sensation because the
      musculocutaneous nerve can drive hand sensation directly or via communication
      with the radial and median nerves. OBJECTIVE: To investigate sensory recovery in
      the hand and forearm after C5 root grafting to the musculocutaneous nerve in
      patients with a total brachial plexus injury. METHODS: Eleven patients who had
      recovered elbow flexion after musculocutaneous nerve grafting from a preserved C5
      root and who had been followed for a minimum of 3 years were screened for sensory
      recovery in the hand and forearm. Six matched patients who had not undergone
      surgery served as controls. Methods of assessment included testing for pain
      sensation using Adson forceps, cutaneous pressure threshold measurements using
      Semmes-Weinstein monofilaments, and the static 2-point discrimination test. Deep
      sensation was evaluated by squeezing the first web space, and thermal sensation
      was assessed using warm and cold water. RESULTS: All grafted patients recovered
      sensation in a variable territory extending from just over the thenar eminence to
      the entire lateral forearm and hand. Seven patients were capable of perceiving 2
      0 monofilament pressure on the thenar eminence, palm, and dorsoradial aspect of
      the hand. All could differentiate warm and cold water. None recovered 2-point
      discrimination. None of the patients in the control group recovered any kind of
      sensation in the affected limb. CONCLUSION: Grafting the musculocutaneous nerve
      can restore nociceptive sensation on the radial side of the hand.

PMID- 22472558
TI  - Isolation of myogenic stem cells from cultures of cryopreserved human skeletal
      muscle.
AB  - We demonstrate that subpopulations of adult human skeletal muscle-derived stem
      cells, myogenic endothelial cells (MECs), and perivascular stem cells (PSCs) can
      be simultaneously purified by fluorescence-activated cell sorting (FACS) from
      cryopreserved human primary skeletal muscle cell  cultures (cryo-hPSMCs). For
      FACS isolation, we utilized a combination of cell lineage markers: the myogenic
      cell marker CD56, the endothelial cell marker UEA-1 receptor (UEA-1R), and the
      perivascular cell marker CD146. MECs expressing all three cell lineage markers
      (CD56(+)UEA-1R(+)CD146(+)/CD45(-))  and PSCs expressing only CD146
      (CD146(+)/CD45(-)CD56(-)UEA-1R(-)) were isolated by FACS. To evaluate their
      myogenic capacities, the sorted cells, with and without expansion in culture,
      were transplanted into the cardiotoxin-injured skeletal  muscles of
      immunodeficient mice. The purified MECs exhibited the highest regenerative
      capacity in the injured mouse muscles among all cell fractions tested, while PSCs
      remained superior to myoblasts and the unpurified primary skeletal muscle cells.
      Our findings show that both MECs and PSCs  retain their high myogenic potentials
      after in vitro expansion, cryopreservation, and FACS sorting. The current study
      demonstrates that myogenic stem cells are prospectively isolatable from long-term
      cryopreserved primary skeletal muscle cell cultures. We emphasize the potential
      application  of this new approach to extract therapeutic stem cells from human
      muscle cells cryogenically banked for clinical purposes.

PMID- 22472559
TI  - Profiling thiol redox proteome using isotope tagging mass spectrometry.
AB  - Pseudomonas syringae pv. tomato strain DC3000 not only causes bacterial speck
      disease in Solanum lycopersicum but also on Brassica species, as well as on
      Arabidopsis thaliana, a genetically tractable host plant(1,2). The accumulation
      of reactive oxygen species (ROS) in cotyledons inoculated with DC3000 indicates a
      role of ROS in modulating necrotic cell death during bacterial speck disease of
      tomato(3). Hydrogen peroxide, a component of ROS, is produced after inoculation
      of tomato plants with Pseudomonas(3). Hydrogen peroxide can be detected using a
      histochemical stain 3'-3' diaminobenzidine (DAB)(4). DAB staining reacts with
      hydrogen peroxide to produce a brown stain on the leaf tissue(4). ROS has a
      regulatory role of the cellular redox environment, which can change the redox
      status of certain proteins(5). Cysteine is an important amino acid sensitive to
      redox changes. Under mild oxidation, reversible oxidation of cysteine sulfhydryl
      groups serves as redox sensors and signal transducers that regulate a variety of
      physiological processes(6,7). Tandem mass tag (TMT) reagents enable concurrent
      identification and multiplexed quantitation of proteins in different samples
      using tandem mass spectrometry(8,9). The cysteine-reactive TMT (cysTMT) reagents
      enable selective labeling and relative quantitation of cysteine-containing
      peptides from up to six biological samples. Each isobaric cysTMT tag has the same
      nominal parent mass and is composed of a sulfhydryl-reactive group, a MS-neutral
      spacer arm and an MS/MS reporter(10). After labeling, the samples were subject to
      protease digestion. The cysteine-labeled peptides were enriched using a resin
      containing anti-TMT antibody. During MS/MS analysis, a series of reporter ions
      (i.e., 126-131 Da) emerge in the low mass region, providing information on
      relative quantitation. The workflow is effective for reducing sample complexity,
      improving dynamic range and studying cysteine modifications. Here we present
      redox proteomic analysis of the Pst DC3000 treated tomato (Rio Grande) leaves
      using cysTMT technology. This high-throughput method has the potential to be
      applied to studying other redox-regulated physiological processes.

PMID- 22472560
TI  - Transmissibility of caprine scrapie in ovine transgenic mice.
AB  - BACKGROUND: The United States control program for classical ovine scrapie is
      based in part on the finding that infection is typically spread through exposure
      to shed placentas from infected ewes. Transmission from goats to sheep is less
      well described. A suitable rodent model for examining the effect of caprine
      scrapie isolates in the ovine host will be useful in the ovine scrapie
      eradication effort. In this study, we describe the incubation time, brain lesion
      profile, glycoform pattern and PrPSc distribution patterns in a well
      characterized transgenic mouse line (Tg338) expressing the ovine VRQ prion
      allele, following inoculation with brain from scrapie infected goats. RESULTS:
      First passage incubation times of caprine tissue in Tg338 ovinized mice varied
      widely but second passage intervals were shorter and consistent. Vacuolation
      profiles, glycoform patterns and paraffin-embedded tissue blots from terminally
      ill second passage mice derived from sheep or goat inocula were similar.
      Proteinase K digestion products of murine tissue were slightly smaller than the
      original ruminant inocula, a finding consistent with passage of several ovine
      strains in previous reports. CONCLUSIONS: These findings demonstrate that Tg338
      mice propagate prions of caprine origin and provide a suitable baseline for
      examination of samples identified in the expanded US caprine scrapie surveillance
      program.

PMID- 22472561
TI  - Collagenase does not persist in human islets following isolation.
AB  - Optimal human islet isolation requires the delivery of bacterial collagenase to
      the pancreatic islet-exocrine interface. However, we have previously demonstrated
      the presence of collagenase within human islets immediately following intraductal
      collagenase administration. This potentially has significant implications for
      patient safety. The present study aimed to determine if collagenase becomes
      internalized into islets during the isolation procedure and if it remains within
      the islet postisolation. Islet samples were taken at various stages throughout 14
      clinical human islet isolations: during digest collection, following University
      of Wisconsin solution incubation, immediately postisolation, and after 24 h of
      culture. Samples were embedded in agar, cryosectioned, and then assessed by
      immunolabeling for collagenase and insulin. Immunoreactivity for collagenase was
      not observed in isolated islets in any preparation. Collagenase labeling was
      detected in one sample taken at the digest collection phase in one islet
      preparation only. No collagenase-specific labeling was seen in islets sampled at
      any of the other time points in any of the 14 islet preparations. Collagenase
      that enters islets during intraductal administration is washed out of the islets
      during the collection phase of the isolation process and thus does not remain in
      islets after isolation. This observation alleviates some of the important safety
      concerns that collagenase remains within islet grafts.

PMID- 22472562
TI  - Distinct metabolic surrogates predict basal and rebound GH secretion after
      glucose ingestion in men.
AB  - CONTEXT: GH secretion declines rapidly after glucose ingestion and then recovers
      to higher-than-baseline levels (rebound GH release). HYPOTHESIS: Selective
      metabolic markers predict the magnitude of glucose-suppressed GH release and
      postglucose rebound-like GH secretion. DESIGN: Prospectively randomized crossover
      study of GH secretion after glucose vs. water ingestion. SETTING: The study was
      conducted at a clinical translational research center. PARTICIPANTS: Sixty-nine
      healthy men aged 19-78 yr with a body mass index of 18-39 kg/m(2) participated in
      the study. OUTCOMES: OUTCOMES included nadir vs. peak GH concentrations and basal
      vs. pulsatile GH secretion. RESULTS: Mean nadir GH concentrations were determined
      positively by sex hormone binding globulin (SHBG) after glucose administration
      (R(2) = 0.088, P = 0.0077). Peak rebound GH concentrations were related
      positively to adiponectin and negatively to computed tomography-estimated
      abdominal visceral fat (AVF) (R(2) = 0.182, P = 0.00049) after glucose ingestion.
      Deconvolution analysis showed that SHBG specifically predicted basal
      (nonpulsatile) GH secretion after glucose exposure (R(2) = 0.153, P = 0.00052).
      In contrast, together exercise history and adiponectin (both positively) and AVF
      (negatively) predicted pulsatile GH escape after glucose suppression (R(2) =
      0.206, P = 0.00043). Moreover, adiponectin uniquely determined the size (mass),
      and AVF the mode (duration), of GH secretory bursts after glucose exposure (both
      P < 0.006). CONCLUSION: Glucose ingestion provides a clinical model for
      investigating complementary metabolic surrogates that determine suppression and
      recovery of basal and pulsatile GH secretion in healthy men.

PMID- 22472563
TI  - Anti-Mullerian hormone is a marker of gonadotoxicity in pre- and postpubertal
      girls treated for cancer: a prospective study.
AB  - CONTEXT: Cytotoxic treatment may accelerate depletion of the primordial follicle
      pool, leading to impaired fertility and premature menopause. Assessment of
      ovarian damage in prepubertal girls is not currently possible, but Anti-Mullerian
      Hormone (AMH) is a useful marker of ovarian reserve in adults. OBJECTIVE: The
      objective of the study was to prospectively evaluate AMH measurement in children
      as a marker of ovarian toxicity during cancer treatment. DESIGN AND SETTING: This
      was a prospective, longitudinal study at a University Hospital. PATIENTS: Twenty
      two females (17 prepubertal), median age 4.4 yr (range 0.3-15 yr), were recruited
      before treatment for cancer. MAIN OUTCOME MEASURES: AMH, inhibin B, and FSH at
      diagnosis, after each chemotherapy course and during follow-up, were measured.
      Risk of gonadotoxicity was classified as low/medium (n = 13) or high (n = 9)
      based on chemotherapy agent, cumulative dose, and radiotherapy involving the
      ovaries. RESULTS: Pretreatment AMH was detectable across the age range studied.
      AMH decreased progressively during chemotherapy (P < 0.0001) in both prepubertal
      and pubertal girls, becoming undetectable in 50% of patients, with recovery in
      the low/medium risk groups after completion of treatment. In the high-risk group,
      AMH became undetectable in all patients and showed no recovery. Inhibin B was
      undetectable in most patients before treatment and, with FSH, showed no clear
      relationship to treatment. CONCLUSION: AMH is detectable in girls of all ages and
      falls rapidly during cancer treatment in both prepubertal and pubertal girls.
      Both the fall during treatment and recovery thereafter varied with risk of
      gonadotoxicity. AMH is therefore a clinically useful marker of damage to the
      ovarian reserve in girls receiving treatment for cancer.

PMID- 22472564
TI  - Circulating microRNA profiles as potential biomarkers for diagnosis of papillary
      thyroid carcinoma.
AB  - CONTEXT: There are no known effective and reliable biomarkers to distinguish
      benign thyroid nodules from papillary thyroid carcinomas (PTC). Previous studies
      have indicated that serum microRNA (miRNA) profiles may be diagnostic and/or
      prognostic markers for numerous other cancers. OBJECTIVE: We studied circulating
      miRNA profiles in patients with PTC or benign nodules and healthy controls to
      identify serum miRNA that may be useful as markers for PTC. DESIGN, SETTING, AND
      PARTICIPANTS: Genome-wide serum miRNA expression profiles were determined using
      Solexa sequencing followed by extensive quantitative RT-PCR validation in 245
      subjects (106 patients with PTC, 95 patients with benign nodules, and 44 healthy
      controls). A panel of miRNA was used to assess the expression of specific miRNA
      in the sera and thyroid tissues of patients with PTC or benign nodules. RESULTS:
      The expression of serum let-7e, miR-151-5p, and miR-222 was significantly
      increased in PTC cases relative to benign cases and healthy controls. Receiver
      operating characteristic curve analyses indicated that use of these three miRNA
      had a high diagnostic sensitivity and specificity for PTC. Serum let-7e, miR-151
      5p, and miR-222 levels were found to be well correlated with certain
      clinicopathological variables, such as nodal status, tumor size, multifocal
      lesion status, and Tumor-Node-Metastasis stage. Expression of serum miR-151-5p
      and miR-222 in a subset of PTC patients decreased significantly after tumor
      excision. Increased expression of miR-151-5p and miR-222 was also found in the
      tissue of PTC patients. CONCLUSIONS: Our study demonstrates that serum miRNA
      profiles may be used as novel and minimally invasive diagnostic markers for PTC.

PMID- 22472565
TI  - Clinical review: Turner syndrome: updating the paradigm of clinical care.
AB  - CONTEXT: Turner syndrome (TS), in which there is loss of all or part of one sex
      chromosome, occurs in one in 2500 live-born females and is associated with
      characteristic findings. Detailed healthcare checklists and screening guidelines
      are commonly used to detect known complications affecting individuals with TS.
      Even with the use of these guidelines, there remains an increased morbidity and
      mortality seen in TS as compared to the general population, leading to
      significant controversy on optimal management of several aspects of TS. EVIDENCE
      ACQUISITION AND SYNTHESIS: A PubMed search of articles from the past 15 yr
      identified available studies related to the diagnosis and management of common
      issues related to TS as well as important historical articles. This review
      summarizes studies through January 2012 and highlights recent developments.
      CONCLUSIONS: There remain many areas of uncertainty in the diagnosis and
      management of TS. Generalizations from experience in the care of other conditions
      in isolation (such as poor growth, follow-up of cardiac disease, or the treatment
      of ovarian failure) cannot be broadly applied when caring for individuals with
      TS. Specific differences include treatment of growth failure as early as
      possible; acquisition of adequate baseline cardiac studies, followed by serial
      magnetic resonance imaging, targeted to identify findings unique to TS that
      address the increased risk of aortic dissection; initiation of hormone
      replacement at the normal age of puberty, preferentially with transdermal
      estradiol; and detailed patient counseling to explain the long-term health risks
      commonly associated with this disorder. A revised paradigm of care using a
      standardized multidisciplinary evaluation, supplementing screening tests as
      advocated by expert opinion guidelines, can aid clinicians in interpreting the
      results of diagnostic testing in the context of TS. This approach optimizes
      medical care for women with TS and may reduce the increased morbidity and
      mortality currently seen in this population.

PMID- 22472566
TI  - Peak expiratory flow rate shows a gender-specific association with vitamin D
      deficiency.
AB  - CONTEXT: To our knowledge, no previous studies examined the longitudinal
      relationship between vitamin D status and pulmonary function in a population
      based sample of older persons. OBJECTIVE: Our objective was to examine the cross
      sectional as well as the longitudinal relationship between vitamin D status and
      peak expiratory flow rate (PEFR) in a representative sample of the Dutch older
      population. DESIGN, SETTING, AND PARTICIPANTS: Participants included men and
      women in the Longitudinal Aging Study Amsterdam, an ongoing cohort study in older
      people. MAIN OUTCOME MEASURE: PEFR was measured using the mini-Wright peak flow
      meter. RESULTS: Men with serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml
      (25 nmol/liter) had a significantly lower PEFR in the cross-sectional analyses,
      and men with serum 25-OHD levels below 20 ng/ml (50 nmol/liter) had a
      significantly lower PEFR in the longitudinal analyses as compared with men with
      serum 25-OHD levels above 30 ng/ml (75 nmol/liter) (cross-sectional: beta = 
      47.0, P = 0.01 for serum 25-OHD <10 ng/ml; longitudinal: beta = -45.0, P < 0.01
      for serum 25-OHD <10 ng/ml; and beta = -20.2, P = 0.03 for serum 25-OHD = 10-20
      ng/ml in the fully adjusted models). Physical performance (beta = -32.5, P = 0.08
      for serum 25-OHD <10 ng/ml) and grip strength (beta = -40.0, P = 0.03 for serum
      25-OHD <10 ng/ml) partly mediated the cross-sectional associations but not the
      longitudinal associations. In women, statistically significant associations
      between 25-OHD and PEFR were observed in the cross-sectional analyses after
      adjustment for age and season of blood collection but not in the fully adjusted
      models or in the longitudinal analyses. CONCLUSIONS: A strong relationship
      between serum 25-OHD and PEFR was observed in older men, both in the cross
      sectional as well as longitudinal analyses, but not in older women. The
      association in men could partly be explained by physical performance and muscle
      strength.

PMID- 22472567
TI  - DNA methylation profiling identifies global methylation differences and markers
      of adrenocortical tumors.
AB  - CONTEXT: It is not known whether there are any DNA methylation alterations in
      adrenocortical tumors. OBJECTIVE: The objective of the study was to determine the
      methylation profile of normal adrenal cortex and benign and malignant
      adrenocortical tumors. METHODS: Genome-wide methylation status of CpG regions
      were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8),
      and metastatic malignant (n = 12) adrenocortical tissue samples. An integrated
      analysis of genome-wide methylation and mRNA expression in benign vs. malignant
      adrenocortical tissue samples was also performed. RESULTS: Methylation profiling
      revealed the following: 1) that methylation patterns were distinctly different
      and could distinguish normal, benign, primary malignant, and metastatic tissue
      samples; 2) that malignant samples have global hypomethylation; and 3) that the
      methylation of CpG regions are different in benign adrenocortical tumors by
      functional status. Normal compared with benign samples had the least amount of
      methylation differences, whereas normal compared with primary and metastatic
      adrenocortical carcinoma samples had the greatest variability in methylation
      (adjusted P <= 0.01). Of 215 down-regulated genes (>=2-fold, adjusted P <= 0.05)
      in malignant primary adrenocortical tumor samples, 52 of these genes were also
      hypermethylated. CONCLUSIONS: Malignant adrenocortical tumors are globally
      hypomethylated as compared with normal and benign tumors. Methylation profile
      differences may accurately distinguish between primary benign and malignant
      adrenocortical tumors. Several differentially methylated sites are associated
      with genes known to be dysregulated in malignant adrenocortical tumors.

PMID- 22472568
TI  - Accuracy and sensitivity of Parkinsonian disorder diagnoses in two Swedish
      national health registers.
AB  - BACKGROUND: Swedish population-based national health registers are widely used
      data sources in epidemiological research. Register-based diagnoses of Parkinson's
      disease have not been validated against clinical information. METHODS:
      Parkinson's disease (PD) and other parkinsonian disorder diagnoses were
      ascertained in two registers, i.e. the National Patient Register (NPR) and the
      Cause of Death Register (CDR). Diagnoses were validated in terms of accuracy
      (positive predictive value) and sensitivity against data from a population-based
      study of PD in 1998-2004 that screened more than 35,000 persons and identified
      194 cases of parkinsonian disorders including 132 PD cases (the gold standard for
      the purposes of this study). RESULTS: Accuracy for any parkinsonian disorder
      diagnoses was 88.0% in the NPR and 94.4% in the CDR. Accuracy of PD diagnoses was
      70.8% in the NPR and 66.7% in the CDR. Misclassification between differential
      parkinsonian diagnoses was common. The accuracy of PD diagnoses in the NPR
      improved to 83.0% by restricting the definition to primary diagnoses only. The
      sensitivity of PD diagnoses in the NPR and CDR combined was 83.1%, with a mean
      time to detection of 6.9 years. CONCLUSIONS: Population-based national health
      registers are valid data sources in epidemiological studies of PD or parkinsonian
      disorder etiology but are less suitable in studies of incidence or prevalence.

PMID- 22472569
TI  - MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and
      metastasis of osteosarcoma cells.
AB  - MicroRNAs are important gene regulators that play a profound role in
      tumorigenesis. MicroRNA-145 (miR-145), an important member in the family of
      microRNAs, is under-expressed in several types of tumors and acts as a tumor
      suppressor. The role and probable pathways of miR-145 in osteosarcoma
      carcinogenesis are still unknown. In this study, we found that miR-145 was
      significantly under-expressed in osteosarcoma tissues, and the over-expression of
      miR-145 could inhibit invasion and angiopoiesis of osteosarcoma cells.
      Furthermore, the results showed that vascular endothelial growth factor (VEGF)
      expression was down-regulated in osteosarcoma cells after miR-145 transfection.
      On the basis of these results, we performed the luciferase assay and verified
      that miR-145 could down-regulate VEGF at the translational level by partially
      binding to VEGF 3' untranslated region (3'UTR). Therefore, it can be concluded
      that miR-145 can inhibit invasion and metastasis of osteosarcoma cells. One of
      the mechanisms is the down-regulation of VEGF expression by miR-145 by binding to
      the 3'UTR of VEGF mRNA specifically. These novel findings may have extensive
      implications for an effective gene therapy of osteosarcoma.

PMID- 22472570
TI  - Neuronal conditional knockout of NRSF decreases vulnerability to seizures induced
      by pentylenetetrazol in mice.
AB  - Neuron restrictive silencer factor (NRSF), also known as repressor element-1
      silencing transcription factor, has been reported to modulate neuronal
      excitability and acts as endogenous anticonvulsant in kainic acid-induced or
      kindling-evoked seizure activity. However, whether NRSF functions in
      pentylenetetrazol (PTZ)-induced seizure activity has never been studied. To
      investigate the role of endogenous NRSF in the epileptogenesis induced by PTZ, in
      our experiment, NRSF neuronal conditional knockout mice (NRSF cKO) were adopted,
      in which NRSF was specifically deleted in neurons by the Cre-loxP system. Seizure
      threshold for PTZ, including the dose-response convulsions and the threshold
      dose, was compared between NRSF cKO and control mice. The threshold dose of PTZ
      that induced clonic and tonic seizures was significantly higher in NRSF cKO mice
      compared with the control. Similarly, the median lethal dose (LD(50)) of PTZ in
      NRSF cKO mice was also considerably higher than that of the control mice. These
      results revealed that NRSF cKO mice are of higher resistance to convulsions
      induced by PTZ. Our work first demonstrated the function of NRSF in PTZ-induced
      seizure and provided new evidence for differential pathways in diverse types of
      seizure.

PMID- 22472571
TI  - Vibrio inhibens sp. nov., a novel bacterium with inhibitory activity against
      Vibrio species.
AB  - Strain BFLP-10(T), isolated from faeces of wild long-snouted seahorses
      (Hippocampus guttulatus), is a Gram-negative, motile and facultatively anaerobic
      rod. This bacterium produces inhibitory activity against Vibrio species.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain BFLP
      10(T) was a member of the genus Vibrio and was most closely related to Vibrio
      owensii (99%), Vibrio communis (98.9%), Vibrio sagamiensis (98.9%) and Vibrio
      rotiferianus (98.4%). However, multilocus sequence analysis using gyrB, pyrH,
      recA and topA genes revealed low levels of sequence similarity (<91.2%) with
      these closely related species. In addition, strain BFLP-10(T) could be readily
      differentiated from other closely related species by several phenotypic
      properties and fatty acid profiles. The G+C content of the DNA was 45.6 mol%. On
      the basis of phenotypic, chemotaxonomic and phylogenetic data, strain BFLP-10(T)
      represents a novel species within the genus Vibrio, for which the name Vibrio
      inhibens sp. nov. is proposed. The type strain is BFLP-10(T) (=CECT 7692(T)=DSM
      23440(T)).

PMID- 22472572
TI  - Inostamycin enhanced TRAIL-induced apoptosis through DR5 upregulation on the cell
      surface.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been
      considered as a possible therapeutic agent for cancer treatment. This is because
      of its selective cytotoxicity against various cancer cells without a detrimental
      effect on normal cells. However, recent studies have reported that the potential
      application of TRAIL in cancer therapy is limited, as many cancer cells have been
      found to be resistant to TRAIL. Therefore, small molecule compounds that
      potentiate the cytotoxicity of TRAIL would be strategic candidates for
      therapeutic applications in combination with TRAIL. Here we found that a combined
      treatment of inostamycin and TRAIL synergistically induced caspase-dependent
      apoptosis in HCT116 cells. Inostamycin upregulated DR5, and a knockdown of DR5
      suppressed the apoptosis that was synergistically induced by co-treatment with
      inostamycin and TRAIL. Moreover, inostamycin increased the expression of DR5 on
      the cell surface. Therefore, inostamycin-increased cell surface expression of DR5
      may have contributed to the enhancement of TRAIL-induced apoptosis. Our study
      suggests that combined treatment with inostamycin and TRAIL may offer a strategy
      to overcome TRAIL resistance in tumor cells.

PMID- 22472573
TI  - Functional investigation of bilateral posterior cingulate gyri using multivoxel
      MR spectroscopy.
AB  - The exact functional correlation of each hemisphere's posterior cingulate gyrus
      with the symptoms of Alzheimer's disease (AD) remains unknown. We attempted to
      evaluate the relationship between metabolite ratios in each hemisphere's
      posterior cingulate gyrus and cognitive deficits, using multivoxel magnetic
      resonance spectroscopy (MRS). We recruited 23 patients with AD, 16 patients with
      amnestic mild cognitive impairment and 22 cognitively normal subjects. All
      patients underwent multivoxel MRS in the bilateral posterior cingulate gyri. We
      statistically analyzed correlations between the N-acetylaspartate/creatine ratio
      (NAA/Cr) in each posterior cingulate gyrus and patients' raw scores on
      neuropsychological tests. The NAA/Cr of each posterior cingulate gyrus correlated
      well with the verbal learning test scores on immediate recall and delayed recall
      tasks. We found that the only cognitive domain to correlate with the NAA/Cr of
      each posterior cingulate gyrus was verbal memory. Our results did not show any
      significant functional difference between right and left posterior cingulate
      gyri.

PMID- 22472574
TI  - The influence of anticipation of word misrecognition on the likelihood of
      stuttering.
AB  - This study investigates whether the experience of stuttering can result from the
      speaker's anticipation of his words being misrecognized. Twelve adults who
      stutter (AWS) repeated single words into what appeared to be an automatic speech
      recognition system. Following each iteration of each word, participants provided
      a self-rating of whether they stuttered on it and the computer then provided
      feedback implying its correct or incorrect recognition of it. Each word was
      repeated four times. Unbeknown to participants, 'Correct' and 'Incorrect'
      recognition of words by the system was pre-determined and bore no relation to the
      actual quality of participants' iterations of those words. For words uttered in
      the 'Correct recognition' condition, the likelihood of AWS self-reporting
      stuttering on a word diminished across iterations, whereas for words in the
      'Incorrect recognition' condition it remained static. On the basis of the
      findings it is argued that: (a) in AWS, the anticipation that a word will be
      misrecognized increases the relative likelihood of stuttering on that word in the
      future; and (b) this effect is independent of the degree of difficulty inherent
      in the formulation and motor execution of the word itself, although it may
      interact with it. Mechanisms that can account for these findings and yet are also
      congruent with the wider range of evidence from psycholinguistic and speech motor
      control domains are discussed. It is concluded that stuttered disfluencies may
      best be explained as resulting from the inappropriate functioning of covert
      repair and/or variable release threshold mechanisms in response to the
      anticipation of communication failure. LEARNING OUTCOMES: This article informs
      readers about two different theoretical approaches to explaining developmental
      stuttering: (1) stuttering as an adaptation response to an underlying impairment;
      and (2) stuttering as an anticipatory struggle response. It describes how these
      approaches account for different symptoms of the disorder, and proposes that both
      theoretical approaches are needed in order to fully account for the range of
      symptoms and experimental findings associated with stuttering.

PMID- 22472575
TI  - A novel hypothesis for the etiology of Graves' disease: TSAb may be thyroid
      stimulating animal IgG-like hormone and TBAb may be the precursor of TSAb.
AB  - There are doubtful points about the theory that autoimmunity with auto-antibody
      (Ab) to TSH receptor (R) causes hyperthyroidism in Graves' disease (GD). A main
      doubtful point is no curative effect of corticosteroid on Graves' hyperthyroidism
      in spite of curative effect of corticosteroid for all autoimmune diseases.
      Recently we demonstrated the immunological similarity of TSAb and TBAb-IgG to
      animal IgGs, except for human (h)IgG, by neutralization and purification of TSAb
      and TBAb-IgG using (1) heterophilic Ab to animal IgG in GD sera and (2)
      experimentally generated anti-animal IgG Abs [such as dog (d), bovine (b),
      porcine (p), and rabbit (rb)]. Furthermore, greater immunological similarity of
      Fab- and F(ab')(2)-portion of TSAb- and TBAb-IgG to bovine Fab, compared to hFab,
      was demonstrated using goat anti-bovine F(ab')(2) Ab. Existence of b and p TSH
      like portions in the LATS-IgG molecule (probably Fab portion) was suggested by a
      previous report of neutralization of LATS activity by anti-b- or anti-p-TSH Ab.
      We suggested the existence of a mammalian animal-TSH-like structure, excepting
      hTSH, in the TSAb-IgG molecule (probably Fab portion), by discovery of anti
      mammalian TSH Ab (such as d, b, p, guinea-pig, rat, whale, except h) in sera of
      GD. Lately, similar TSHR binding of H- and L-chain of human stimulating
      monoclonal TSHR Ab (M22)-Fab with TSH-alpha and-beta subunit was reported. This
      evidence suggests that Fab portion of TSAb has a structure like mammalian TSH,
      but not hTSH. IgG-lambda type of d, horse, b, p, goat, ovine is 95% and IgG-kappa
      type is 5%, while human kappa and lambda chain is 60:40. Previous report that
      LATS (TSAb)-IgG composed of predominant lambda type is supporting evidence that
      TRAb-IgG has immunological similarity with these animal IgGs compared to hIgG. We
      speculate that TSAb-IgG may be referred as a mermaid consisted in face (Fab) and
      trunk-leg (Fc). Face may be a kind of hormone with animal TSH-like structure and
      trunk-leg has animal IgG-like structure (in spite of no antibody function). There
      are many reports for co-existence of TSAb and TBAb-IgG in sera of GD. We reported
      conversion from TBAb (non-thyroid stimulating type IgG) to TSAb by co-incubation
      of anti-hIgG Ab (containing anti-animal IgG Ab as a cross-reaction) with TBAb
      bound porcine thyroid cells. Thus, we suggest that TBAb may be the precursor form
      of TSAb.

PMID- 22472577
TI  - Determinants of neighborhood activity of adults age 70 and over: a mixed-methods
      study.
AB  - BACKGROUND: This mixed-methods study investigated personal, interpersonal, and
      environmental factors salient to decisions about being active in neighborhoods of
      different levels of deprivation. METHODS: Twenty-five participants age 70 years
      and older (10 women) with diverse physical activity levels provided data on their
      weekly activity patterns (using accelerometry) and their perceived barriers to
      exercise (questionnaire). They also participated in semistructured individual
      interviews exploring the barriers and facilitators influencing neighborhood
      activity. RESULTS: Functional limitations, lack of intrinsic motivation, and not
      having an activity companion were the highest impact barriers. Walkable access to
      amenities, positive physical activity perceptions, and existing habit of being
      active were the highest impact facilitators. CONCLUSIONS: The perceived quality
      and accessibility of the built and natural environments influence neighborhood
      activity in older adults. However, this relationship might be altered through the
      influence of personal and interpersonal determinants such as maintenance of good
      health and functional ability and supportive social networks.

PMID- 22472578
TI  - Effects of strength and power training on neuromuscular variables in older
      adults.
AB  - The purpose of this study was to compare the neuromuscular adaptations produced
      by strength-training (ST) and power-training (PT) regimens in older individuals.
      Participants were balanced by quadriceps cross-sectional area (CSA) and leg-press
      1-repetition maximum and randomly assigned to an ST group (n = 14; 63.6 +/- 4.0
      yr, 79.7 +/- 17.2 kg, and 163.9 +/- 9.8 cm), a PT group (n = 16; 64.9 +/- 3.9 yr,
      63.9 +/- 11.9 kg, and 157.4 +/- 7.7 cm), or a control group (n = 13; 63.0 +/- 4.0
      yr, 67.2 +/- 10.8 kg, and 159.8 +/- 6.8 cm). ST and PT were equally effective in
      increasing (a) maximum dynamic and isometric strength (p < .05), (b) increasing
      quadriceps muscle CSA (p < .05), and (c) decreasing electrical mechanical delay
      of the vastus lateralis muscle (p < .05). There were no significant changes in
      neuromuscular activation after training. The novel finding of the current study
      is that PT seems to be an attractive alternative to regular ST to maintain and
      improve muscle mass.

PMID- 22472580
TI  - Effects of exercise on health-related quality of life and fear of falling in home
      dwelling older women.
AB  - This randomized, controlled trial evaluated the effects of exercise on health
      related quality of life (HRQoL) and fear of falling (FoF) among 149 home-dwelling
      older women. The 12-mo exercise program was intended to reduce the risk of falls
      and fractures. HRQoL was assessed by the RAND-36 Survey, and FoF, with a visual
      analog scale, at baseline, 12 mo, and 24 mo. On all RAND-36 scales, the scores
      indicated better health and well-being. The exercise had hardly any effect on
      HRQoL; only the general health score improved slightly compared with controls at
      12 mo (p = .019), but this gain was lost at 24 mo. FoF decreased in both groups
      during the intervention with no between-groups difference at 12 or 24 mo. In
      conclusion, despite beneficial physiological changes, the exercise intervention
      showed rather limited effects on HRQoL and FoF among relatively high-functioning
      older women. This modest result may be partly because of insufficient
      responsiveness of the assessment instruments used.

PMID- 22472581
TI  - Aging and well-being in French older adults regularly practicing physical
      activity: a self-determination perspective.
AB  - The purpose of this study was to identify the motivational profiles of physically
      active older adults and to achieve a better understanding of their perceived
      motives to explain their regular physical activity behavior in relation to self
      determination theory (SDT). To address these aims, this study used quantitative
      and qualitative approaches. Older adults (n = 92; M = 74.95, SD = 4.6) completed
      the French version of the Sport Motivational Scale. A cluster analysis showed two
      motivational profiles with differential motivational patterns. The first was
      named the high combined profile, with high scores on intrinsic motivation and
      introjected regulation and low levels of external regulation. The second profile
      was the low to moderate motivational profile, with low scores on intrinsic
      motivation and moderate scores on introjected regulation. The qualitative study's
      results demonstrate the usefulness of SDT in explaining the relationship between
      these motivational profiles and the intertwining of the three basic psychological
      needs.

PMID- 22472582
TI  - Evidence for the construct validity of self-motivation as a correlate of exercise
      adherence in French older adults.
AB  - OBJECTIVES: Exercise adherence involves a number of sociocognitive factors that
      influence the adoption and maintenance of regular physical activity. Among trait
      like factors, self-motivation is believed to be a unique predictor of persistence
      during behavior change. The aim of this study was to validate the factor
      structure of a French version of the Self-Motivation Inventory (SMI) and to
      provide initial convergent and discriminant evidence for its construct validity
      as a correlate of exercise adherence. METHOD: Four hundred seventy-one elderly
      were recruited and administered the SMI-10. Structural equation modeling tested
      the relation of SMI-10 scores with exercise adherence in a correlated network
      that included decisional balance and perceived quality of life. RESULTS:
      Acceptable evidence was found to support the factor validity and measurement
      equivalence of the French version of the SMI-10. Moreover, self-motivation was
      related to exercise adherence independently of decisional balance and perceived
      quality of life, providing initial evidence for construct validity.

PMID- 22472584
TI  - Building better hospital transfusion committees for Ontario.
AB  - Hospital transfusion committees can be instrumental in ensuring appropriate blood
      utilization and that best practice standards are followed. In Ontario, Canada,
      the provincial Ministry of Health and Long-Term Care Blood Programs Coordinating
      Office has implemented several initiatives to support these multi-disciplinary
      hospital committees to fulfill their mandate. The primary goal is to improve
      patient safety and the secondary goal is to reinforce the importance of
      appropriate use of blood components and blood products. Recognizing the
      challenges in developing a fully functional hospital transfusion committee,
      several initiatives have been launched to provide educational resources and tools
      to achieve a successful outcome. The number of hospital transfusion committees in
      Ontario has increased over the past 5 years. Attendance at the annual educational
      forum for transfusion committees continues to be high. The majority of hospitals
      are using the resources and tools being provided. More work is needed to achieve
      the success of this strategy.

PMID- 22472585
TI  - Probiotic supplements (Lactobacillus reuteri DSM 17938 and ATCC PTA 5289) do not
      affect regrowth of mutans streptococci after full-mouth disinfection with
      chlorhexidine: a randomized controlled multicenter trial.
AB  - The aim of this study was to investigate the effectiveness of tablets containing
      two probiotic Lactobacillus reuteri strains in inhibiting regrowth of salivary
      mutans streptococci (MS) after full-mouth disinfection (FMD) with chlorhexidine.
      The null hypothesis was that the levels of MS would not differ in comparison with
      a placebo protocol. The study population was comprised of 62 young adults (mean
      age 23 years) with moderate or high counts of salivary MS who volunteered after
      informed consent. The study was a double-blinded randomized controlled trial with
      two parallel groups. After a 3-day chlorhexidine regimen, the subjects were
      randomly assigned to a test group (n = 32) with probiotic lozenges (2/day) or a
      placebo group (n = 30). The intervention period was 6 weeks, and stimulated whole
      saliva was collected at baseline and after 1, 6, and 12 weeks. The samples were
      processed for MS by a chair-side test and DNA-DNA hybridization as an estimate of
      19 bacterial strains associated with oral health and disease. There was no
      significant difference between the groups at inclusion, and FMD reduced the
      salivary MS levels significantly in both groups. The MS suppression lasted less
      than 6 weeks and there were no statistical differences in salivary MS regrowth
      between the test and control groups at any of the follow-ups. Likewise, there
      were no major differences in the regrowth patterns of the checkerboard panel
      between the two groups. We conclude that daily oral administration of L. reuteri
      did not seem to affect or delay the regrowth of salivary MS after FMD with
      chlorhexidine.

PMID- 22472586
TI  - Reflecting on evidence-based practice: International Nurses Day.

PMID- 22472587
TI  - Gallbladder perforation: Mystery continues to unravel.

PMID- 22472588
TI  - Urologic oncology: Poor trial accrual hinders germ cell tumor therapy advances.

PMID- 22472589
TI  - Prostate cancer: 11 years follow-up for ERSPC.

PMID- 22472593
TI  - Urothelial carcinoma: Endoscopy to predict outcomes in upper tract urothelial
      cancer.

PMID- 22472595
TI  - Intracerebroventricular transplantation of human bone marrow-derived multipotent
      progenitor cells in an immunodeficient mouse model of mucopolysaccharidosis type
      I (MPS-I).
AB  - Mucopolysaccharidosis type I (MPS-I; Hurler syndrome) is an inborn error of
      metabolism caused by lack of the functional lysosomal glycosaminoglycan (GAG)
      degrading enzyme alpha-L-iduronidase (IDUA). Without treatment, the resulting GAG
      accumulation causes multisystem dysfunction and death within the first decade.
      Current treatments include allogeneic hematopoietic stem cell transplantation
      (HSCT) and enzyme replacement therapy. HSCT ameliorates clinical features and
      extends life but is not available to all patients, and inadequately corrects the
      most devastating features of the disease including mental retardation and
      skeletal deformities. Recent developments suggest that stem cells can be used to
      deliver needed enzymes to the central nervous system. To test this concept, we
      transplanted bone marrow-derived normal adult human MultiStem(r) cells into the
      cerebral lateral ventricles of immunodeficient MPS-I neonatal mice. Transplanted
      cells and human-specific DNA were detected in the hippocampal formation,
      striatum, and other areas of the central nervous system. Brain tissue assays
      revealed significant long-term decrease in GAG levels in the hippocampus and
      striatum. Sensorimotor testing 6 months after transplantation demonstrated
      significantly improved rotarod performance of transplanted mice in comparison to
      nontransplanted and sham-transplanted control animals. These results suggest that
      a single injection of MultiStem cells into the cerebral ventricles of neonatal
      MPS-I mice induces sustained reduction in GAG accumulation within the brain, and
      modest long-term improvement in sensorimotor function.

PMID- 22472596
TI  - Impaired axoplasmic transport is the dominant injury induced by an impact
      acceleration injury device: an analysis of traumatic axonal injury in pyramidal
      tract and corpus callosum of rats.
AB  - Traumatic axonal injury (TAI) involves neurofilament compaction (NFC) and
      impaired axoplasmic transport (IAT) in distinct populations of axons. Previous
      quantification studies of TAI focused on limited areas of pyramidal tract (Py)
      but not its entire length. Quantification of TAI in corpus callosum (CC) and its
      comparison to that in Py is also lacking. This study assessed and compared the
      extent of TAI in the entire Py and CC of rats following TBI. TBI was induced by a
      modified Marmarou impact acceleration device in 31 adult male Sprague Dawley rats
      by dropping a 450 gram impactor from either 1.25 m or 2.25 m. Twenty-four hours
      after TBI, TAI was assessed by beta amyloid precursor protein (beta-APP-IAT) and
      RMO14 (NFC) immunocytochemistry. TAI density (beta-APP and RMO14 axonal
      swellings, retraction balls and axonal profiles) was counted from panoramic
      images of CC and Py. Significantly high TAI was observed in 2.25 m impacted rats.
      beta-APP immunoreactive axons were significantly higher in number than RMO14
      immunoreactive axons in both the structures. TAI density in Py was significantly
      higher than in CC. Based on our parallel biomechanical studies, it is inferred
      that TAI in CC may be related to compressive strains and that in Py may be
      related to tensile strains. Overall, IAT appears to be the dominant injury type
      induced by this model and injury in Py predominates that in CC.

PMID- 22472597
TI  - Interactions between NMDA and dopamine receptors: a potential therapeutic target.
AB  - Many pathological processes are associated with a malfunction of one or multiple
      post-synaptic neurotransmitter receptors. It would seem that simple agonists or
      antagonists at these receptors should be able to correct the pathological
      condition. However, these drugs often fail due to serious side effects that are
      caused by suppressing post-synaptic responses necessary for normal brain
      function. Thus, there is a need for new drugs that can selectively target
      specific post-synaptic pathways. The dopamine and glutamate receptor systems have
      been implicated in many neuropsychiatric disorders. Dopamine, the predominant
      catecholamine in the mammalian brain, influences a variety of functions including
      locomotor activity, cognition, emotion and endocrine regulation. Glutamate is the
      principal excitatory neurotransmitter, involved in regulating neuronal circuit
      development, learning and memory. The overlap and convergence of both
      dopaminergic and glutamatergic projections in the brain provides a framework for
      complex neuronal interactions between these receptor systems. In this review, we
      will focus on interactions between the NMDA glutamate receptor and dopamine D1
      and D2 receptors, and address the potential value of receptor heteromers in
      seeking novel therapeutic targets. This article is part of a Special Issue
      entitled: Brain Integration.

PMID- 22472598
TI  - Dominant optic atrophy, neuropathy, ataxia, white matter FLAIR hypersignals,
      middle cerebellar peduncule atrophy and asthenia in OPA1 mutation.

PMID- 22472599
TI  - Interaction between adipose tissue-derived mesenchymal stem cells and regulatory
      T-cells.
AB  - Mesenchymal stem cells (MSCs) exhibit immunosuppressive capabilities, which have
      evoked interest in their application as cell therapy in transplant patients. So
      far it has been unclear whether allogeneic MSCs and host regulatory T-cells
      (Tregs) functionally influence each other. We investigated the interaction
      between both cell types using perirenal adipose tissue-derived MSCs (ASCs) from
      kidney donors and Tregs from blood bank donors or kidney recipients 6 months
      after transplantation. The immunomodulatory capacity of ASCs was not prejudiced
      by both Tregs from healthy donors and Tregs from graft recipients, indicating
      that ASCs were not targeted by the inhibitory effects of Tregs and vice versa. In
      addition, Tregs supported ASC function, as they did not alter the secretion of
      IFN-gamma by immune cells and hence contributed to ASC activation and efficiency.
      ASCs exerted their suppressive role by expressing IDO, reducing levels of TNF
      alpha, and by inducing the production of IL-10 in effector cells and Tregs. In
      conclusion, this study presents evidence that donor ASCs and acceptor Tregs do
      not impair each other's function and therefore encourages the use of MSC therapy
      for the prevention of graft rejection in solid organ transplantation.

PMID- 22472600
TI  - Central nervous system drug consumption depending on the time between symptom
      onset and the diagnosis of Alzheimer's disease: an analysis by the Registry of
      Dementias of Girona.
AB  - AIMS: To describe central nervous system (CNS) drug consumption patterns
      depending on the time to diagnosis of Alzheimer's disease (AD), and to check
      whether the cases diagnosed later are associated with greater severity and
      consuming more CNS drugs. METHODS: Cross-sectional study using 952 cases of the
      Registry of Dementias of Girona. A binary logistic regression was used to detect
      variables associated with the use of CNS drugs depending on the time to
      diagnosis. RESULTS: CNS drugs were consumed by 95.8% of the AD patients. Only
      antipsychotics presented a statistically significant increase in the frequency of
      prescription to patients with longer time elapsed from symptom onset to AD
      diagnosis. CONCLUSION: Longer time elapsed from the onset of symptoms to the
      diagnosis resulted in increased probability of antipsychotic consumption.

PMID- 22472601
TI  - Endurance training protocol and longitudinal performance assays for Drosophila
      melanogaster.
AB  - One of the most pressing problems facing modern medical researchers is the
      surging levels of obesity, with the consequent increase in associated disorders
      such as diabetes and cardiovascular disease (1-3).  An important topic of
      research into these associated health problems involves the role of endurance
      exercise as a beneficial intervention.    Exercise training is an inexpensive,
      non-invasive intervention with several beneficial results, including reduction in
      excess body fat (4), increased insulin sensitivity in skeletal muscle (5),
      increased anti-inflammatory and antioxidative responses (6), and improved
      contractile capacity in cardiomyocytes (7). Low intensity exercise is known to
      increase mitochondrial activity and biogenesis in humans (8) and mice, with the
      transcriptional coactivator PGC1-alpha as an important intermediate (9,10).    
      Despite  the importance of exercise as a tool for combating several important 
      age-related diseases, extensive longitudinal genetic studies have been impeded 
      by the lack of an endurance training protocol for a short-lived genetic model 
      species. The  variety of genetic tools available for use with Drosophila,
      together with its short lifespan and inexpensive  maintenance, make it an
      appealing model for further study of these genetic  mechanisms. With this in mind
      we have developed a novel apparatus, known as the  Power Tower, for large scale
      exercise-training in Drosophila melanogaster (11). The Power Tower utilizes the
      flies'  instinctive negative geotaxis behavior to repetitively induce rapid
      climbing. Each time the machine lifts, then drops, the  platform of flies, the
      flies are induced to climb. Flies continue to respond as  long as the machine is
      in operation or until they become too fatigued to  respond. Thus, the researcher
      can use this machine to provide simultaneous  training to large numbers of age
      matched and genetically identical flies.  Additionally, we describe associated
      assays useful to track longitudinal  progress of fly cohorts during training.

PMID- 22472602
TI  - Highlights from recently determined structures of membrane proteins: a focus on
      channels and transporters.
AB  - After decades of absent or lackluster growth, recent years have at long last
      witnessed an exponential growth in the number of novel membrane protein
      structures determined. Every single achievement has had a tremendous impact on
      the scientific community, providing an unprecedented wealth of information that
      typically only an atomic resolution structure can contribute to our molecular
      understanding of how a protein functions. Presented here is a review of some of
      the most exciting novel structures of channels and transporters determined by X
      ray crystallography in the last two years, and a discussion of their analogies,
      differences and mechanistic implications.

PMID- 22472603
TI  - AIMP1 deficiency enhances airway hyperreactivity in mice via increased TH2 immune
      responses.
AB  - Aminoacyl tRNA synthetase complex-interacting multicomplex protein 1 (AIMP1) is
      known as a novel cytokine carrying out a variety of biological activities,
      including angiogenesis and wound repair. In our previous reports AIMP1 was
      demonstrated to induce TH1 polarization. However, the effects of AIMP1 deficiency
      in TH1 or TH2 immune disorders remain unclear. In this study, we characterized
      phenotypes of AIMP1-deficient mice and investigated the role of AIMP1 in TH2
      biased airway hyperreactivity. Clinical signs of allergic airway inflammation
      were assessed in AIMP1-deficient mice and the effects of AIMP1 deficiency on
      production of TH2 cytokines were evaluated in T cells using AIMP1-specific siRNA.
      Additionally, the enhanced pause values and histologic analysis were assessed in
      mice receiving AIMP1-deficient CD4+ T cells with OVA challenge. Clinical signs of
      spontaneous airway inflammation were noted in AIMP1-deficienct mice. AIMP1
      deficient mice showed strongly increased Penh values in response to methacholine
      without any allergen exposure. Adoptive transfer of AIMP1-deficient CD4+ T cells
      to OVA-sensitized C57BL/6 mice exacerbated OVA-induced airway inflammation and
      increased infiltration of inflammatory cells into the lung. Furthermore, lung DCs
      in AIMP1-deficient mice showed increased expression of surface molecules, and IL
      12p40 level in sera significantly decreased in AIMP1-deficient mice compared to
      that of wild type mice. These results strongly indicate that AIMP1 plays a role
      in negatively regulating TH2 responses in vivo, and AIMP1 can be employed as a
      novel therapeutic agent against TH2-biased diseases, particularly asthma.

PMID- 22472604
TI  - Noninvasive MRI measurement of CBF: evaluating an arterial spin labelling
      sequence with 99mTc-HMPAO CBF autoradiography in a rat stroke model.
AB  - Arterial spin labelling (ASL) is increasingly available for noninvasive cerebral
      blood flow (CBF) measurement in stroke research. Here, a pseudo-continuous ASL
      technique (pCASL) was evaluated against (99m)Tc-D, L-hexamethylpropyleneamine
      oxime ((99m)Tc-HMPAO) autoradiography in a rat stroke model. The (99m)Tc-HMPAO
      was injected (intravenously, 225 MBq) during pCASL acquisition. The pCASL and
      (99m)Tc-HMPAO autoradiography CBF measures, relative to the contralateral
      hemisphere, were in good agreement across the spectrum of flow values in normal
      and ischemic tissues. The pCASL-derived quantitative regional CBF values
      (contralateral: 157 to 177 mL/100 g per minute; ipsilateral: 9 to 104 mL/100 g
      per minute) were consistent with the literature values. The data show the
      potential utility of pCASL for CBF assessment in a rat stroke model.

PMID- 22472605
TI  - Menage a trois: the role of neurotransmitters in the energy metabolism of
      astrocytes, glutamatergic, and GABAergic neurons.
AB  - This work is a computational study based on a new detailed metabolic network
      model comprising well-mixed compartments representing separate cytosol and
      mitochondria of astrocytes, glutamatergic and gamma aminobutyric acid (GABA)ergic
      neurons, communicating through an extracellular space compartment and fed by
      arterial blood flow. Our steady-state analysis assumes statistical mass balance
      of both carbons and amino groups. The study is based on Bayesian flux balance
      analysis, which uses Markov chain Monte Carlo sampling techniques and provides a
      quantitative description of steady states when the two exchangers aspartate
      glutamate carrier (AGC1) and oxoglutarate carrier (OGC) in the malate-aspartate
      shuttle in astrocyte are not in equilibrium, as recent studies suggest. It also
      highlights the importance of anaplerotic reactions, pyruvate carboxylase in
      astrocyte and malic enzyme in neurons, for neurotransmitter synthesis and
      recycling. The model is unbiased with respect to the glucose partitioning between
      cell types, and shows that determining the partitioning cannot be done by
      stoichiometric constraints alone. Furthermore, the intercellular lactate
      trafficking is found to depend directly on glucose partitioning, suggesting that
      a steady state may support different scenarios. At inhibitory steady state,
      characterized by high rate of GABA release, there is elevated oxidative activity
      in astrocyte, not in response to specific energetic needs.

PMID- 22472606
TI  - ABC transporter function and regulation at the blood-spinal cord barrier.
AB  - We present here an initial characterization of ATP binding cassette (ABC)
      transporter function and regulation at the blood-spinal cord barrier. We isolated
      capillaries from rat spinal cords and studied transport function using a confocal
      microscopy-based assay and protein expression using western blots. These
      capillaries exhibited transport function and protein expression of P-glycoprotein
      (Abcb1), multidrug resistance protein 2 (Mrp2, Abcc2), and breast cancer-related
      protein (Bcrp, Abcg2). Exposing isolated capillaries to dioxin (activates aryl
      hydrocarbon receptor) increased transport mediated by all three transporters.
      Brain and spinal cord capillaries from dioxin-dosed rats exhibited increased P
      glycoprotein-mediated transport and increased protein expression for all three
      ABC transporters. These findings indicate similar ABC transporter expression,
      function, and regulation at the blood-spinal cord and blood-brain barriers.

PMID- 22472607
TI  - Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain
      binding affinity of the PET radioligand [(18)F]-FEPPA.
AB  - [(18)F]-FEPPA binds to the 18-kDa translocator protein (TSPO) and is used in
      positron emission tomography (PET) to detect microglial activation. However,
      quantitative interpretations of the PET signal with new generation TSPO PET
      radioligands are confounded by large interindividual variability in binding
      affinity. This presents as a trimodal distribution, reflecting high-affinity
      binders (HABs), low-affinity binder (LAB), and mixed-affinity binders (MABs).
      Here, we show that one polymorphism (rs6971) located in exon 4 of the TSPO gene,
      which results in a nonconservative amino-acid substitution from alanine to
      threonine (Ala147Thr) in the TSPO protein, predicts [(18)F]-FEPPA total
      distribution volume in human brains. In addition, [(18)F]-FEPPA exhibits clearly
      different features in the shape of the time activity curves between genetic
      groups. Testing for the rs6971 polymorphism may allow quantitative interpretation
      of TSPO PET studies with new generation of TSPO PET radioligands.

PMID- 22472608
TI  - Neuroglobin regulates hypoxic response of neuronal cells through Hif-1alpha- and
      Nrf2-mediated mechanism.
AB  - Oxygen sensing in hypoxic neurons has been classically attributed to cytochrome c
      oxidase and prolyl-4-hydroxylases and involves stabilization of transcription
      factors, hypoxia-inducible factor-1alpha (Hif-1alpha) and nuclear factor
      erythroid 2-related factor 2 (Nrf2) that mediate survival responses. On the
      contrary, release of cytochrome c into the cytosol during hypoxic stress triggers
      apoptosis in neuronal cells. We, here advocate that the redox state of
      neuroglobin (Ngb) could regulate both Hif-1alpha and Nrf2 stabilization and
      cytochrome c release during hypoxia. The hippocampal regions showing higher
      expression of Ngb were less susceptible to global hypoxia-mediated
      neurodegeneration. During normoxia, Ngb maintained cytochrome c in the reduced
      state and prevented its release from mitochondria by using cellular antioxidants.
      Greater turnover of oxidized cytochrome c and increased utilization of cellular
      antioxidants during acute hypoxia altered cellular redox status and stabilized
      Hif-1alpha and Nrf2 through Ngb-mediated mechanism. Chronic hypoxia, however,
      resulted in oxidation and degradation of Ngb, accumulation of ferric ions and
      release of cytochrome c that triggered apoptosis. Administration of N-acetyl
      cysteine during hypoxic conditions improved neuronal survival by preventing Ngb
      oxidation and degradation. Taken together, these results establish a role for Ngb
      in regulating both the survival and apoptotic mechanisms associated with hypoxia.

PMID- 22472610
TI  - Highlights: Transcranial imaging of functional cerebral hemodynamic changes in
      single blood vessels.

PMID- 22472609
TI  - Deletion of astroglial connexins weakens the blood-brain barrier.
AB  - Astrocytes, the most prominent glial cell type in the brain, send specialized
      processes named endfeet, which enwrap blood vessels and express a large molecular
      repertoire dedicated to the physiology of the vascular system. One of the most
      striking properties of astrocyte endfeet is their enrichment in gap junction
      protein connexins 43 and 30 (Cx43 and Cx30) allowing for direct intercellular
      trafficking of ions and small signaling molecules through perivascular astroglial
      networks. The contribution of astroglial connexins to the physiology of the brain
      vascular system has never been addressed. Here, we show that Cx43 and Cx30
      expression at the level of perivascular endfeet starts from postnatal days 2 and
      12 and is fully mature at postnatal days 15 and 20, respectively, indicating that
      astroglial perivascular connectivity occurs and develops during postnatal blood
      brain barrier (BBB) maturation. We demonstrate that mice lacking Cx30 and Cx43 in
      GFAP (glial fibrillary acidic protein)-positive cells display astrocyte endfeet
      edema and a partial loss of the astroglial water channel aquaporin-4 and beta
      dystroglycan, a transmembrane receptor anchoring astrocyte endfeet to the
      perivascular basal lamina. Furthermore, the absence of astroglial connexins
      weakens the BBB, which opens upon increased hydrostatic vascular pressure and
      shear stress. These results demonstrate that astroglial connexins are necessary
      to maintain BBB integrity.

PMID- 22472611
TI  - Measurement of 5-HT(1A) receptor density and in-vivo binding parameters of
      [(18)F]mefway in the nonhuman primate.
AB  - The goal of this work was to characterize the in-vivo behavior of [(18)F]mefway
      as a suitable positron emission tomography (PET) radiotracer for the assay of 5
      hydroxytryptamine(1A) (5-HT(1A)) receptor density (B(max)). Six rhesus monkeys
      were studied using a multiple-injection (M-I) protocol consisting of three
      sequential bolus injections of [(18)F]mefway. Injection times and amounts of
      unlabeled mefway were optimized for the precise measurement of B(max) and
      specific binding parameters k(off) and k(on) for estimation of apparent K(D). The
      PET time series were acquired for 180 minutes with arterial sampling performed
      throughout. Compartmental analysis using the arterial input function was
      performed to obtain estimates for K(1), k(2), k(off), B(max), and K(Dapp) in the
      cerebral cortex and raphe nuclei (RN) using a model that accounted for nontracer
      doses of mefway. Averaged over subjects, highest binding was seen in the mesial
      temporal and dorsal anterior cingulate cortices with B(max) values of 42+/-8 and
      36+/-8 pmol/mL, respectively, and lower values in the superior temporal cortex,
      RN, and parietal cortex of 24+/-4, 19+/-4, and 13+/-2 pmol/mL, respectively. The
      K(Dapp) of mefway for the 5-HT(1A) receptor sites was 4.3+/-1.3 nmol/L. In
      conclusion, these results show that M-I [(18)F]mefway PET experiments can be used
      for the in-vivo measurement of 5-HT(1A) receptor density.

PMID- 22472612
TI  - Transcranial imaging of functional cerebral hemodynamic changes in single blood
      vessels using in vivo photoacoustic microscopy.
AB  - Optical imaging of changes in total hemoglobin concentration (HbT), cerebral
      blood volume (CBV), and hemoglobin oxygen saturation (SO(2)) provides a means to
      investigate brain hemodynamic regulation. However, high-resolution transcranial
      imaging remains challenging. In this study, we applied a novel functional
      photoacoustic microscopy technique to probe the responses of single cortical
      vessels to left forepaw electrical stimulation in mice with intact skulls.
      Functional changes in HbT, CBV, and SO(2) in the superior sagittal sinus and
      different-sized arterioles from the anterior cerebral artery system were
      bilaterally imaged with unambiguous 36 * 65-MUm(2) spatial resolution. In
      addition, an early decrease of SO(2) in single blood vessels during activation
      (i.e., 'the initial dip') was observed. Our results indicate that the initial dip
      occurred specifically in small arterioles of activated regions but not in large
      veins. This technique complements other existing imaging approaches for the
      investigation of the hemodynamic responses in single cerebral blood vessels.

PMID- 22472614
TI  - Making connexons in the neurovascular unit.

PMID- 22472613
TI  - Topology and hemodynamics of the cortical cerebrovascular system.
AB  - The cerebrovascular system continuously delivers oxygen and energy substrates to
      the brain, which is one of the organs with the highest basal energy requirement
      in mammals. Discontinuities in the delivery lead to fatal consequences for the
      brain tissue. A detailed understanding of the structure of the cerebrovascular
      system is important for a multitude of (patho-)physiological cerebral processes
      and many noninvasive functional imaging methods rely on a signal that originates
      from the vasculature. Furthermore, neurodegenerative diseases often involve the
      cerebrovascular system and could contribute to neuronal loss. In this review, we
      focus on the cortical vascular system. In the first part, we present the current
      knowledge of the vascular anatomy. This is followed by a theory of topology and
      its application to vascular biology. We then discuss possible interactions
      between cerebral blood flow and vascular topology, before summarizing the
      existing body of the literature on quantitative cerebrovascular topology.

PMID- 22472615
TI  - Audiological and subjective benefit results in bone-anchored hearing device
      users.
AB  - OBJECTIVE: Audiological and subjective benefits in adult bone-anchored hearing
      device users. STUDY DESIGN: Retrospective evaluation. SETTING: Tertiary referral
      center. PATIENTS: Thirty-eight adult subjects fitted with unilateral bone
      anchored hearing device. INTERVENTIONS: Audiometric measurements included sound
      field pure-tone and speech audiometries (speech reception threshold, maximum
      speech discrimination). Subjective benefit was assessed by the Abbreviated
      Profile of Hearing Aid Benefit (APHAB) questionnaire. Ipsilateral and
      contralateral hearing loss was considered. Comparison was drawn between Compact,
      Divino, and Intenso processors. MAIN OUTCOME: To compare sound-field pure-tone
      and speech audiometries and APHAB results with and without the device adjusted
      for the unaided results. RESULTS: With the device, sound-field pure-tone
      audiometry results revealed an increase gain in all frequencies. Sound-field
      speech audiometry showed that the mean threshold of speech recognition was 20 dB
      lower, maximum discrimination was attained at 5 dB less, and percentage of
      maximum discrimination increased by 5%. Scores in the APHAB questionnaire
      decreased except for the aversiveness subscale. Auditory-adjusted gain showed
      greater benefit in subjects with ipsilateral conductive hearing loss.Subjects
      with contralateral normal hearing or conductive hearing loss showed greater
      improvement that those with contralateral mixed or sensorineural hearing loss.
      There were no differences between Compact, Divino and Intenso processors.
      CONCLUSION: When comparisons are adjusted for unaided condition, the bone
      anchored hearing device provided auditory and subjective benefit in subjects with
      ipsilateral conductive hearing loss and contralateral normal hearing or
      conductive hearing loss. It gave marginal benefit in ipsilateral mixed and
      contralateral mixed or sensorineural hearing loss. No differences were found
      between the Compact, Intenso, and Divino processors.

PMID- 22472616
TI  - Turning Dicer on its head.
AB  - Recent structural analysis of full-length human Dicer supports a new model of the
      enzyme's domain arrangement and provides a structural basis for many of Dicer's
      biochemical attributes.

PMID- 22472617
TI  - A 3D framework for understanding enterovirus 71.
AB  - Two papers report the structure of the virion of emerging pathogen EV71,
      providing a three-dimensional context for understanding many of its biological
      functions.

PMID- 22472623
TI  - Proteinuria and glomerular damage in Rab3A knockout mice chronically fed a high
      glucose diet.
AB  - BACKGROUND/AIMS: The relative contribution of genetic factors and dietary
      patterns to glomerular damage in healthy individuals and prediabetic conditions
      is currently unclear. All Rab3A knockout (KO) mice spontaneously develop
      macroalbuminuria, but only male mice exhibit a glucose-intolerant phenotype, thus
      making the model suitable to examine the impact of a diet on preexisting podocyte
      damage. METHODS: Male and female Rab3A KO and wild-type (WT) mice were
      chronically fed a high-glucose diet (HGD). Biochemical tests, histology and
      immunohistochemistry were periodically performed whilst primary podocytes served
      for in vitro analyses. RESULTS: Chronic administration of an HGD did not induce
      de novo alterations in WT kidneys but caused progressive worsening of podocyte
      and glomerular damage in both male and female Rab3A KO. Though glomerular
      lesions, reminiscent of human diabetic nephropathy, were more severe in male
      mice, overt proteinuria and renal damage were also evident in female mice. The in
      vitro analysis of Rab3A WT and KO podocytes revealed diminished actin plasticity
      in the cell processes of KO podocytes. Furthermore, a modest increase in glucose
      concentration induced profound cytoskeletal changes only in Rab3A KO cells.
      CONCLUSIONS: Our data show that chronic administration of an HGD to Rab3A KO mice
      that have a genetic defect that impairs podocyte actin plasticity results in
      increased podocyte damage and leads to overt proteinuria. If the same diet is
      given to male Rab3A KO animals, with additionally altered glucose homeostasis,
      this results in renal lesions similar to those of human diabetic nephropathy.

PMID- 22472622
TI  - High-resolution structure of infectious prion protein: the final frontier.
AB  - Prions are the proteinaceous infectious agents responsible for the transmission
      of prion diseases. The main or sole component of prions is the misfolded prion
      protein (PrP(Sc)), which is able to template the conversion of the host's
      natively folded form of the protein (PrP(C)). The detailed mechanism of prion
      replication and the high-resolution structure of PrP(Sc) are unknown. The
      currently available information on PrP(Sc) structure comes mostly from low
      resolution biophysical techniques, which have resulted in quite divergent models.
      Recent advances in the production of infectious prions, using very pure
      recombinant protein, offer new hope for PrP(Sc) structural studies. This review
      highlights the importance of, challenges for and recent progress toward
      elucidating the elusive structure of PrP(Sc), arguably the major pending
      milestone to reach in understanding prions.

PMID- 22472624
TI  - Anaesthesia and orphan disease: phocomelia--a lesson from the past.

PMID- 22472625
TI  - Bilateral lingual nerve injury associated with classic laryngeal mask airway:  a
      case report.

PMID- 22472627
TI  - Job satisfaction, stress and burnout in anaesthesia:  relevant topics for
      anaesthesiologists and healthcare managers?
AB  - Job satisfaction is defined as an employee's positive reaction towards his/her
      work. Changes in health policies, which are seen as a threat to the autonomy of
      health workers, are associated with a decrease in satisfaction levels, increase
      burnout among physicians, and may impair the quality and safety of care. The work
      environment of anaesthesiologists include stressful areas such as the operating
      theatre, the ICU, and the emergency setting, and this has been linked to higher
      levels of stress and lower satisfaction. We frequently lack feedback from
      patients and even our colleagues despite usually working within a team.
      Nevertheless, job satisfaction and burnout rates in anaesthesia are similar to
      other specialties. The most relevant factors in job satisfaction are worker
      autonomy, control of the working environment, recognition of our value,
      professional relationships, leadership and organisational justice. Although these
      can be manipulated for good or otherwise, there are additional, less malleable
      factors such as personality, expectations and motivation of the employee, that
      play a part. Within organisations there needs to be the will to evaluate
      employees' satisfaction, to improve their work environment and to develop
      strategies and coping mechanisms for professional stress. Personal wellness
      should also be nurtured, as a satisfactory work-life balance and an adequate
      social support network might act as a buffer for dissatisfaction and burnout.
      Improvement in satisfaction might create a positive work climate that would
      benefit both the safety of our patients and our profession.

PMID- 22472628
TI  - Management of spinal anaesthesia-induced hypotension for caesarean delivery:  a
      European survey.

PMID- 22472629
TI  - Diet and dietary-niche breadth of diurnal rain forest primates in the Central
      Western Ghats, India.
AB  - We studied the feeding ecology of 3 sympatric primate species, the lion-tailed
      macaque (Macaca silenus), bonnet macaque (Macaca radiata) and Hanuman langur
      (Semnopithecus entellus), in a tropical rain forest of the Central Western Ghats,
      India. Since the availability of leaves is much higher than that of fruits, we
      expected that the primarily folivorous langurs would use a larger number of
      resources than the primarily frugivorous macaques. Since fruits are a relatively
      total resource, unlike leaves, of which only selected parts are consumed, we
      expected that the primarily frugivorous macaques would use resources more
      proportionately than the folivorous langurs, resulting in a wider food niche
      breadth in macaques. We collected data on these primate species over a period of
      2 years using scan sampling in a contiguous rain forest. We calculated Levin's
      standardised food niche breadth for each species. Langurs used a larger number of
      tree species than macaques, but their niche breadth was narrower than that of
      macaques. The majority of their diet (over 50%) came from only a few trees in the
      case of all three primate species. Long-term data are provided herein for the
      first time on the feeding ecology of bonnet macaques and Hanuman langurs in a
      tropical rain forest.

PMID- 22472630
TI  - Investigation of genome instability in exfoliated colonic epithelial cells and in
      mitogen-stimulated lymphocytes of patients with ulcerative colitis.
AB  - OBJECTIVE: The present study aimed to evaluate the micronucleus (MN),
      nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated
      lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN
      frequency in exfoliated colonic epithelial cells obtained from both the diseased
      and healthy colonic mucosa of patients. DESIGN: The study was conducted in 22
      newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD
      values scored in binucleated (BN) cells were obtained from the mitogen-stimulated
      lymphocytes of patients and control subjects. In addition, the MN values in
      exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa
      of patients were evaluated. RESULTS: We found significantly higher MN, NPB and
      NBUD frequencies in the BN cells of patients with UC than in those of the control
      subjects (1.61 +/- 0.75 vs. 0.89 +/- 0.29, 3.93 +/- 1.91 vs. 1.39 +/- 1.10, and
      1.55 +/- 0.89 vs. 0.64 +/- 0.48, p = 0.001). Also, a statistically significant
      difference was found between MN frequencies obtained from the diseased and
      healthy colonic mucosa of patients (1.07 +/- 0.46 vs. 0.59 +/- 0.21, p = 0.001).
      No significant relationship was found between age and MN frequency in patients
      with UC (r = 0.076, p = 0.735). CONCLUSION: Increased MN, NPB and NBUD
      frequencies observed in both the lymphocytes and exfoliated colonic epithelial
      cells obtained from patients with UC may reflect genomic instability.

PMID- 22472631
TI  - Neural induction with neurogenin 1 enhances the therapeutic potential of
      mesenchymal stem cells in an amyotrophic lateral sclerosis mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by progressive dysfunction
      and degeneration of motor neurons in the central nervous system (CNS). In the
      absence of effective drug treatments for ALS, stem cell treatment has emerged as
      a candidate therapy for this disease. To date, however, there is no consensus
      protocol that stipulates stem cell types, transplantation timing, or frequency.
      Using an ALS mouse model carrying a high copy number of a mutant human superoxide
      dismutase-1 (SOD1)(G93A) transgene, we investigated the effect of neural
      induction on the innate therapeutic potential of mesenchymal stem cells (MSCs) in
      relation to preclinical transplantation parameters. In our study, the expression
      of monocyte chemoattractant protein-1 (MCP-1) was elevated in the ALS mouse
      spinal cord. Neural induction of MSCs with neurogenin 1 (Ngn1) upregulated the
      expression level of the MCP-1 receptor, CCR2, and enhanced the migration activity
      toward MCP-1 in vitro. Ngn1-expressing MSCs (MSCs-Ngn1) showed a corresponding
      increase in tropism to the CNS after systemic transplantation in ALS mice.
      Notably, MSCs-Ngn1 delayed disease onset if transplanted during preonset
      ages,whereas unprocessed MSCs failed to do so. If transplanted near the onset
      ages, a single treatment with MSCs-Ngn1 was sufficient to enhance motor functions
      during the symptomatic period (15-17 weeks), whereas unprocessed MSCs required
      repeated transplantation to achieve similar levels of motor function improvement.
      Our data indicate that systemically transplanted MSCs-Ngn1 can migrate to the CNS
      and exert beneficial effects on host neural cells for an extended period of time
      through paracrine functions, suggesting a potential benefit of neural induction
      of transplanted MSCs in long-term treatment of ALS.

PMID- 22472633
TI  - Sleep and television and computer habits of Swedish school-age children.
AB  - The aim of this study was to investigate sleep, television and computer habits
      and enjoyment and feelings of tiredness in school of school-age children and
      adolescents in Sweden. An instrument found to be valid and reliable here was
      distributed to 3,011 children aged 6, 7, 10, 14, and 16 years. Those sleeping
      less than the median length of time reported a significantly lower degree of
      enjoyment of school. Short sleep was found to be associated with having a bedroom
      TV, spending more than 2 hr a day at the TV or the computer, being tired in
      school, and having difficulties both in waking up and in sleeping. Discussing
      sleep and media habits with schoolchildren and their parents regarding matters of
      optimal sleep and of how media habits affect sleep and learning is seen to be an
      important task of the school health service.

PMID- 22472632
TI  - Pilot intervention to increase physical activity among sedentary urban middle
      school girls: a two-group pretest-posttest quasi-experimental design.
AB  - The primary purpose of the study was to determine whether girls in one school
      receiving nurse counseling plus an after-school physical activity club showed
      greater improvement in physical activity, cardiovascular fitness, and body
      composition than girls assigned to an attention control condition in another
      school (N = 69). Linear regressions controlling for baseline measures showed no
      statistically significant group differences, but the directionality of
      differences was consistent with greater intervention group improvement for
      minutes of moderate to vigorous physical activity/hour (t = 0.95, p = .35),
      cardiovascular fitness (t = 1.26, p = .22), body mass index (BMI; t = -1.47, p =
      .15), BMI z score (t = -1.19, p = .24), BMI percentile (t = -0.59, p = .56),
      percentage body fat (t = -0.86, p = .39), and waist circumference (t = -0.19, p =
      .85). Findings support testing with a larger sample.

PMID- 22472634
TI  - Family influences on adolescents' birth control and condom use, likelihood of
      sexually transmitted infections.
AB  - This study explored the relationships among personal factors, family structure
      and family function, adolescents' self-efficacy for safe sex, and sexual
      behaviors among sexually active adolescents. A subset sample from the first three
      waves of the National Longitudinal Study of Adolescent Health (Add Health) was
      selected for this exploratory secondary data analysis. Hierarchal and logistic
      regressions were conducted to explore the relationships among personal factors,
      family factors, and adolescents' self-reported sexually transmitted infections
      (STI) over time. Findings suggest that adolescents' racial/ethnic background,
      parents' disapproving attitudes, and family connectedness are significant
      predictors for birth control and condom use among adolescents. Although
      adolescents' personal factor and family structure play a role in their sexual
      behavior, positive family function significantly protects adolescents from STIs
      over time. School nurses can provide a vital point of care for at-risk
      adolescents by finding ways to encourage and incorporate parental and familial
      influences.

PMID- 22472635
TI  - Overweight and obesity in youth.

PMID- 22472636
TI  - Practices and procedures to prevent the transmission of skin and soft tissue
      infections in high school athletes.
AB  - Skin and soft tissue infections (SSTIs) are frequent in student athletes and are
      often caused by community-associated methicillin-resistant Staphylococcus aureus
      (CA-MRSA). We evaluated the awareness of CA-MRSA among high school coaches and
      athletic directors in Missouri (n = 4,408) and evaluated hygiene practices
      affecting SSTI transmission. Of 1,642 (37%) respondents, 61% received MRSA
      educational information during the past year and 32% indicated their school had
      written guidelines for managing SSTIs in athletes. Coaches and athletic directors
      aware of written guidelines reported a lower incidence of SSTIs in student
      athletes (26%) compared to those without written policies (34%, p = .03). When
      confronted with SSTIs, 49% of respondents referred student athletes to the school
      nurse or a physician. A relationship exists between school policies for SSTI
      management and lower incidence of SSTIs. Educational initiatives by school nurses
      in conjunction with athletic staff may lead to practices that limit SSTIs in this
      at-risk population.

PMID- 22472637
TI  - Effect of pressure and temperature on alcoholic fermentation by Saccharomyces
      cerevisiae immobilized on gamma-alumina pellets.
AB  - Saccharomyces cerevisiae was immobilized on gamma-alumina pellets and used for
      repeated batch fermentations in glucose medium (16.5 g/100 mL) at various
      temperatures and pressures. An increase in pressure from 3 to 7 atm and a
      decrease in temperature from 30 to 20  degrees C reduced the ethanol productivity
      by about 50% and 70%, respectively. Increasing concentrations of volatile by
      products were observed at lower fermentation temperatures, while the pressure
      influence on the concentrations of these by-products was proved to be more
      complex. Mathematical expressions were established to allow the calculation of
      the fermentation rate at various pressures and sugar concentrations when the
      corresponding rate at atmospheric pressure is known. The study showed that the
      height of bioreactors has to be limited to 19.5 m due to hydrostatic pressure
      shock at higher fill levels.

PMID- 22472638
TI  - Performance and robustness of an ANAMMOX anaerobic baffled reactor subjected to
      transient shock loads.
AB  - The impacts of transient overloads on the performance of a laboratory-scale
      anaerobic ammonium oxidation (ANAMMOX) anaerobic baffled reactor was studied by
      increasing the substrate concentration or inflow rate to 1.5-3.0 times above
      normal values. These shocks, with the exception of the highest substrate shock,
      weakened the nitrogen removal efficiency (NRE) but improved the nitrogen removal
      rate by 0.01-0.18 g l(-1) h(-1). The communities and the location of the sludge
      may be altered by distinct types of shocks. The substrate vibration data showed
      that the reactor was unresponsive to hydraulic shocks but sensitive to substrate
      shocks and the former compartments were more susceptible to the shocks. In the
      inhibition period, the pH and NRE of the reactor were related to the residual
      ammonium and free ammonia (FA) and FA was a factor in the reactor fluctuations.
      The Gaussian model proposed to describe the shocks response fits the experimental
      data well.

PMID- 22472639
TI  - Co-digestion of source segregated domestic food waste to improve process
      stability.
AB  - Cattle slurry and card packaging were used to improve the operational stability
      of food waste digestion, with the aim of reducing digestate total ammoniacal
      nitrogen concentrations compared to food waste only. Use of cattle slurry could
      have major environmental benefits through reducing greenhouse gas emissions
      associated with current management practices; whilst card packaging is closely
      linked to food waste and could be co-collected as a source segregated material.
      Both options increase the renewable energy potential whilst retaining organic
      matter and nutrients for soil replenishment. Co-digestion allowed higher organic
      loadings and gave a more stable process. A high ammonia inoculum acclimated more
      readily to cattle slurry than card packaging, probably through supplementation by
      trace elements and micro-organisms. Long-term operation at a 75-litre scale
      showed a characteristic pattern of volatile fatty acid accumulation in mono
      digestion of food waste, and allowed performance parameters to be determined for
      the co-digestion substrates.

PMID- 22472640
TI  - Preparation, structure and anticoagulant activity of a low molecular weight
      fraction produced by mild acid hydrolysis of sulfated rhamnan from Monostroma
      latissimum.
AB  - A low molecular weight fraction, designated LMWP, was prepared by mild acid
      hydrolysis of sulfated rhamnan from Monostroma latissimum and purified by anion
      exchange and gel-permeation chromatography. Chemical and spectroscopic analyses
      showed that LMWP was mainly composed of rhamnose, and its molecular weight was
      about 33.6 kDa. The backbone of LMWP consists of 1,3-linked alpha-L-rhamnose
      units with partially sulfate groups at the C-2 position. Approximately 25% of 1,3
      linked alpha-L-rhamnose units is substituted at C-2 by sulfated or non-sulfated
      1,3-linked alpha-L-rhamnose and 1,2-linked alpha-L-rhamnose units. LMWP
      effectively prolonged clotting time as evaluated by the activated partial
      thromboplastin time assay and was a potent thrombin inhibitor mediated by heparin
      cofactor II. The investigation demonstrated that LMWP is a novel sulfated
      polysaccharide with anticoagulant activity.

PMID- 22472641
TI  - Simultaneous determination of flumatinib and its two major metabolites in plasma
      of chronic myelogenous leukemia patients by liquid chromatography-tandem mass
      spectrometry.
AB  - Flumatinib is an antineoplastic tyrosine kinase inhibitor used for the treatment
      of chronic myelogenous leukemia (CML). Its major metabolites in the circulation
      are N-desmethyl flumatinib (M1) and amide hydrolysis product (M3). To investigate
      the pharmacokinetics of flumatinib in CML patients, a simple, specific and rapid
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      and validated for the simultaneous determination of flumatinib and its two major
      metabolites in patient plasma. After a simple, one-step protein precipitation
      with methanol, flumatinib, its two metabolites, and internal standard (HHGV-E)
      were separated on a C(18) column using an isocratic mobile phase of methanol:5mM
      ammonium acetate:formic acid (60:40:0.4, v/v/v). A total chromatographic run time
      of 4.2 min was achieved. The detection was performed in multiple reaction
      monitoring mode, using the transitions of m/z 563->m/z 463 for flumatinib, m/z
      549->m/z 463 for M1, m/z 303->m/z 175 for M3, and m/z 529->m/z 429 for HHGV-E.
      The method was linear over the concentration ranges of 0.400-400 ng/mL for
      flumatinib, 0.100-100 ng/mL for M1, and 0.200-200 ng/mL for M3, using only 50 MUL
      of plasma. The intra- and inter-day precisions were less than 8.5% for
      flumatinib, 9.8% for M1, and 10.6% for M3 in terms of the relative standard
      deviation. The accuracy was within +/- 2.2% for flumatinib, +/- 6.0% for M1, and
      +/- 9.9% for M3 in terms of relative error. The validated method was successfully
      applied to clinical pharmacokinetic studies of flumatinib mesylate in CML
      patients following oral administration at all dosage regimens.

PMID- 22472642
TI  - Is puberty a trigger for 5HTTLPR polymorphism association with depressive
      symptoms?

PMID- 22472643
TI  - Downregulation of TOMM40 expression in the blood of Alzheimer disease subjects
      compared with matched controls.
AB  - Translocase of outer mitochondrial membrane 40 homolog (TOMM40) gene has been
      reported in several GWAS to be associated with Alzheimer disease (AD). Gene
      expression studies thus far only showed TOMM40 differential expression in one
      study on brain cortex and not in peripheral blood. We studied the gene expression
      profiles of AD blood versus controls in an Asian population in Singapore. In this
      first analysis we focused on genes that have been previously reported on GWAS. We
      found TOMM40 to be significantly down-regulated in blood samples of AD in one
      discovery and two validation sets, totalling 45 subjects (mean age 76.90, SD
      6.46) and 45 controls (mean age 76.23, SD 5.09), matched for ethnicity and
      gender. The function of TOMM40 is not yet fully characterized but is believed to
      be involved in import and trafficking of protein into mitochondria. Therefore
      TOMM40 downregulation, found in the brain in severe AD and in our blood profile,
      may be a potential marker for AD, disease severity or progression and merit
      further investigation.

PMID- 22472644
TI  - Transition to parenthood and substance use disorders: findings from a 30-year
      longitudinal study.
AB  - BACKGROUND: This study examined the associations between the transition to
      parenthood and substance use disorders from ages 18 to 30 in a New Zealand birth
      cohort. METHODS: Outcomes included: DSM-IV criteria for: (a) alcohol
      abuse/dependence (AAD) and (b) illicit substance abuse/dependence. The study also
      used measures transition to parenthood during the period 18-30 years; and
      observed covariate factors including: family socio-economic status; family
      functioning; childhood abuse exposure; childhood personal and behavioural
      characteristics; and psychosocial adjustment in adolescence. Data were analysed
      using repeated measures generalised estimating equation models, and conditional
      fixed effects regression modelling to control for confounding. Gender
      interactions were examined using moderated regression analyses. RESULTS: Those
      who became parents had unadjusted odds of substance use disorder outcomes that
      were approximately 50% lower than those who had not become parents. Adjustment of
      the associations for both: (a) observed confounding factors and (b) non-observed
      fixed effects; strengthened the associations between parenthood status and
      substance use disorders. Custodial parents had odds of substance use disorders
      that were 57-78% lower than those who did not become parents after adjusting for
      non-observed fixed effects. Additional analyses suggested these effects were
      confined to custodial parents only. There was also evidence for gender*parenthood
      status interactions for AAD, with the effects of parenthood on AAD being stronger
      for females. CONCLUSIONS: The results suggest that the transition to custodial
      parenthood may result in reduced risks of substance use disorder, particularly
      amongst female cohort members.

PMID- 22472645
TI  - Effects of donor characteristics and ex vivo expansion on canine mesenchymal stem
      cell properties: implications for MSC-based therapies.
AB  - Clinical trials utilizing bone marrow-derived mesenchymal stem cell (BM-MSC)
      therapies show promise for treating a variety of pathologic conditions. Paramount
      to optimization of such cell-based therapies is a thorough understanding of MSC
      biology. Despite the tremendous potential that  exists for the clinical use of
      canine BM-MSCs in veterinary medicine, as well as in preclinical studies for
      human medicine, relatively little information exists regarding basic biological
      properties of the cells. In this study, we compared the importance of donor
      characteristics (age and harvest  site) and ex vivo expansion on canine BM-MSC
      frequency (CFU-f) and differentiation potential. Advancing age was found to have
      a negative effect on CFU-f as well as osteogenic potential. Site of harvest was
      also found to have significant effects on MSC properties. MSCs obtained from the
      humerus  were found at the lowest frequency and were least osteogenic compared to
      those harvested from the tibia, femur, and ilium. Osteogenic potential diminished
      significantly by the third passage. These results suggest important donor
      parameters and culture effects to consider in translational studies  examining
      MSC-based regenerative medical strategies.

PMID- 22472646
TI  - A TIRF microscopy technique for real-time, simultaneous imaging of the TCR and
      its associated signaling proteins.
AB  - Signaling is initiated through the T Cell Receptor (TCR) when it is engaged by
      antigenic peptide fragments bound by Major Histocompatibility Complex (pMHC)
      proteins expressed on the surface of antigen presenting cells (APCs). The TCR
      complex is composed of the ligand binding TCRalphabeta heterodimer that
      associates non-covalently with CD3 dimers (the epsilondelta and epsilongamma
      heterodimers and the zetazeta homodimer)(1). Upon engagement of the receptor, the
      CD3 zeta chains are phosphorylated by the Src family kinase, Lck. This leads to
      the recruitment of the Syk family kinase, Zap70, which is then phosphorylated and
      activated by Lck. After that, Zap70 phosphorylates the adapter proteins LAT and
      SLP76, initiating the formation of the proximal signaling complex containing a
      large number of different signaling molecules(2).     The formation of this
      complex eventually results in calcium and Ras-dependent transcription factor
      activation and the consequent initiation of a complex series of gene expression
      programs that give rise to T cell differentiation(2). TCR signals (and the
      resulting state of differentiation) are modulated by many other factors,
      including antigen potency and crosstalk with co-stimulatory/co-inhibitory,
      chemokine, and cytokine receptors (3-4). Studying the spatial and temporal
      organization of the proximal signaling complex under various stimulation
      conditions is, therefore, key to understanding the TCR signaling pathway as well
      as its regulation by other signaling pathways.    One very useful model system to
      study signaling initiated by the TCR at the plasma membrane in T cells is glass
      supported lipid bilayers, as described previously(5-6). They can be utilized to
      present antigenic pMHC complexes, adhesion, and co-stimulatory molecules to T
      cells-serving as artificial APCs. By imaging the T cells interacting with the
      lipid bilayer using total internal reflection fluorescence microscopy (TIRFM), we
      can restrict the excitation to within 100 nm of the space between the glass and
      the cell surface (7-8). This allows us to image primarily the signaling events
      occurring at the plasma membrane. As we are interested in imaging the recruitment
      of signaling proteins to the TCR complex, we describe a two-camera TIRF imaging
      system wherein the TCR, labeled with fluorescent Fab (fragment antigen binding)
      fragments of the H57 antibody (purified from hybridoma H57-597, ATCC, ATCC
      Number:HB-218) which is specific for TCRbeta, and signaling proteins, tagged with
      GFP, may be imaged simultaneously and in real time. This strategy is necessary
      due to the highly dynamic nature of both the T cells and of the signaling events
      that are occurring at the TCR. This imaging modality has allowed researchers to
      image single ligands (9-11) as well as recruitment of signaling molecules to
      activated receptors and is an excellent system to study biochemistry in-situ(12
      16).

PMID- 22472647
TI  - You're going to need a bigger (glass bottom) boat.
AB  - Signaling molecules of the transforming growth factor (TGF)-beta family are
      generated from proprotein precursors containing prodomain sequences that are
      typically removed to allow signaling by the mature ligands. A form of a TGF-beta
      family ligand that remains covalently attached to its prodomain but retains
      signaling activity has been identified. Glass bottom boat (Gbb), a Drosophila
      homolog of the bone morphogenetic protein 5/6/7/8 subfamily, is active as a
      carboxyl-terminal fragment of the proprotein (Gbb15) that is generated by a
      conventional processing event common to TGF-beta ligands. Unexpectedly, a larger
      form (Gbb38) produced by processing at a newly identified furin site in the
      prodomain is also secreted and active. Contrary to the present paradigm in which
      TGF-beta ligands require dissociation of the entire prodomain for activity, Gbb38
      is active in cell culture and in vivo without additional processing at
      conventional sites. The large form can restore the viability of gbb mutant
      animals but has distinct signaling properties compared with the conventional
      form. Production of multiple functional ligands from one proprotein is a
      potential mechanism to fine-tune TGF-beta signaling outputs. Mutations in TGF
      beta family members have been linked to human diseases, several of which affect
      potential furin cleavage sites in prodomains. However, given the diversity of
      potential furin processing sites and prodomain functions, direct experimentation
      will be required to determine whether production of active jumbo ligands is a
      general feature of TGF-beta superfamily members.

PMID- 22472649
TI  - Receptor-selective diffusion barrier enhances sensitivity of astrocytic processes
      to metabotropic glutamate receptor stimulation.
AB  - Metabotropic glutamate receptor (mGluR)-dependent calcium ion (Ca2+) signaling in
      astrocytic processes regulates synaptic transmission and local blood flow
      essential for brain function. However, because of difficulties in imaging
      astrocytic processes, the subcellular spatial organization of mGluR-dependent
      Ca2+ signaling is not well characterized and its regulatory mechanism remains
      unclear. Using genetically encoded Ca2+ indicators, we showed that despite global
      stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a
      marked enrichment of Ca2+ responses. Immunocytochemistry indicated that these
      polarized Ca2+ responses could be attributed to increased density of surface
      mGluR5 on processes relative to the soma. Single-particle tracking of surface
      mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5
      between the processes and the soma. Overexpression of mGluR or expression of its
      carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes,
      disrupting the polarization of mGluR5 and of mGluR-dependent Ca2+ signaling.
      Together, our results demonstrate an mGluR5-selective diffusion barrier between
      processes and soma that compartmentalized mGluR Ca2+ signaling in astrocytes and
      may allow control of synaptic and vascular activity in specific subcellular
      domains.

PMID- 22472648
TI  - Astrocytes modulate neural network activity by Ca2+-dependent uptake of
      extracellular K+.
AB  - Astrocytes are electrically nonexcitable cells that display increases in
      cytosolic calcium ion (Ca2+) in response to various neurotransmitters and
      neuromodulators. However, the physiological role of astrocytic Ca2+ signaling
      remains controversial. We show here that astrocytic Ca2+ signaling ex vivo and in
      vivo stimulated the Na+,K+-ATPase (Na+- and K+-dependent adenosine
      triphosphatase), leading to a transient decrease in the extracellular potassium
      ion (K+) concentration. This in turn led to neuronal hyperpolarization and
      suppressed baseline excitatory synaptic activity, detected as a reduced frequency
      of excitatory postsynaptic currents. Synaptic failures decreased in parallel,
      leading to an increase in synaptic fidelity. The net result was that astrocytes,
      through active uptake of K+, improved the signal-to-noise ratio of synaptic
      transmission. Active control of the extracellular K+ concentration thus provides
      astrocytes with a simple yet powerful mechanism to rapidly modulate network
      activity.

PMID- 22472651
TI  - Should children be SCUBA diving?: Cerebral arterial gas embolism in a swimming
      pool.
AB  - Cerebral arterial gas embolism (CAGE) is a well-known serious complication of
      self-contained breathing apparatus (SCUBA) diving. Most serious complications of
      SCUBA diving occur in adults because most of SCUBA divers are adults. However,
      young age is an independent risk factor for injury in SCUBA diving and shallow
      water SCUBA diving is the riskiest environment for CAGE. We present a case of a
      10-year-old boy who developed CAGE while taking SCUBA diving lessons in a
      university swimming pool. This case illustrates the potential danger of SCUBA
      diving for children who lack understanding of the physics of diving as well as
      the often unappreciated risk of shallow-water SCUBA diving. Our intent is to
      educate providers of primary care to children, so that they may appropriately
      advise parents about SCUBA diving, and to educate providers of emergency care to
      children, so that they will recognize this uncommon but serious emergency
      condition.

PMID- 22472652
TI  - No such thing as "just" a nail bed injury.
AB  - Nail bed injuries are the commonest pediatric hand injuries presenting to the
      emergency department. If managed correctly, the patient recovers quickly and
      complications are rare. However, failure to appreciate the complex anatomy of the
      perionychium and the importance of exploration, washout, and repair can result in
      devastating complications. These injuries are often underestimated and,
      consequently, delegated to the most junior and inexperienced staff. The case of a
      6-year-old boy with a flexor sheath infection and devitalized fingertip 1 week
      after injury is presented. Emphasis is placed on the soft tissue and underlying
      bony injury that was overlooked at initial presentation, and how this led to
      serious infection requiring amputation. Thorough assessment of these common
      injuries and a high index of suspicion are essential.

PMID- 22472650
TI  - A large bioactive BMP ligand with distinct signaling properties is produced by
      alternative proconvertase processing.
AB  - Dimers of conventional transforming growth factor-beta (TGF-beta) and bone
      morphogenetic protein (BMP) ligands are composed of two 100- to 140-amino acid
      peptides that are produced through the proteolytic processing of a proprotein
      precursor by proconvertases, such as furin. We report the identification of an
      evolutionarily conserved furin processing site in the amino terminus (NS) of the
      Glass bottom boat (Gbb; the Drosophila ortholog of vertebrate BMP5, 6, and 7)
      proprotein that generates a 328-amino acid, active BMP ligand distinct from the
      conventional 130-amino acid ligand. Gbb38, the large ligand form of Gbb,
      exhibited greater signaling activity and a longer range than the shorter form
      Gbb15. The abundance of Gbb15 and Gbb38 varied among different tissues, raising
      the possibility that differential processing could account for tissue-specific
      behaviors of BMPs. In human populations, mutations that abolished the NS cleavage
      site in BMP4, BMP15, or anti-Mullerian hormone were associated with cleft lip
      with or without cleft palate (BMP4), premature ovarian failure (BMP15), and
      persistent Mullerian duct syndrome (anti-Mullerian hormone), suggesting the
      importance of NS processing during development. The identification of this large
      BMP ligand form and the functional differences between large and small ligands
      exemplifies the potential for differential proprotein processing to substantially
      affect BMP and TGF-beta signaling output in different tissue and cellular
      contexts.

PMID- 22472653
TI  - The effect of magnesium sulfate on uncontrollable contractions in a tetanus case.
AB  - Tetanus is a rare disease caused by the exotoxins of Clostridium tetani. Higher
      mortality rates have been reported among the elderly and in the newborn. In this
      report of a tetanus case, the treatment and prognosis of contractions resistant
      to diazepam, midazolam, and atracurium infusion has been evaluated.

PMID- 22472654
TI  - Influenza A(H1N1)-associated ischemic stroke in a 9-month-old child.
AB  - AIM: This study aimed to report a rare clinical course of pandemic influenza
      A(H1N1) infection, ischemic stroke, in a 9 month-old child. CASE: A 9-month-old
      girl with no previous medical problem presented to our pediatric emergency
      department with high fever (39 degrees C/102 degrees F) lasting for 48 hours.
      Soon after admission, she started generalized tonic-clonic seizures that ceased
      after 2 injections of diazepam. Six hours later, she presented 2 short episodes
      of partial clonic seizures of the right arm followed by monoplegia. Lumbar
      puncture was normal. Noncontrast computed tomographic imaging of the brain was
      performed and revealed an acute infarct in the left middle cerebral artery
      territory with no mass effect. Electroencephalogram revealed important slowing in
      the left hemisphere. A magnetic resonance imaging was performed the next day and
      confirmed an ischemic stroke in the left posterior middle cerebral artery region.
      Nasal swab polymerase chain reaction was positive for influenza A(H1N1) and
      polymerase chain reaction detection negative in cerebrospinal fluid. She fully
      recovered her right-arm function on day 3 and was discharged on day 10 without
      sequelae. COMMENTS: Seasonal influenza is known to cause neurological
      complications in children. Influenza increases the stroke risk especially in
      adults at high risk. This is a rare event in childhood, and we believe this is
      the first report associated with H1N1 new variant. CONCLUSIONS: Acute viral
      infection, notably influenza, is associated with increased susceptibility to
      stroke, and vaccination against influenza may reduce the risk of stroke.

PMID- 22472655
TI  - Management of nonprogressive sharp foreign body in a two year old.
AB  - Foreign body (FB) ingestion is a common and potentially serious problem in the
      pediatric age group. We describe a case of a 2-year-old boy who presented 15 days
      after ingesting a metallic nail. He was asymptomatic since then, and the FB had
      not passed spontaneously. Emergency laparotomy was done, and the FB was removed.
      Spontaneous passage had been inadvertently allowed for 15 days in this case,
      instead of the recommended 3 days. To our knowledge, this is the first case
      report of ingested metallic nail not having passed spontaneously after a period
      of 15 days. Our emphasis on presenting this case report has been on the timely
      surgical intervention.

PMID- 22472656
TI  - Venezuelan equine encephalitis in a teenager visiting Central America.
AB  - BACKGROUND: Stupor, coma, and other alterations of consciousness are among the
      most serious life-threatening emergencies faced by the emergency department
      physician. When a patient arrives with altered mentation from Central or South
      America, the usual causes that occur in the United States must be considered;
      however, other unusual tropical disease must be excluded, such as Venezuelan
      equine encephalitis (VEE). OBJECTIVE: This study aimed to review the clinical
      features of VEE. CASE: A 17-year-old female traveled to Belize and developed
      vomiting, diarrhea, fever, headaches, and myalgias. Over the next few hours, she
      became disoriented and had a generalized seizure. She was given diazepam, 50%
      dextrose, phenytoin, mannitol, and vitamin K. A computed tomographic scan of the
      head was unremarkable. Her parents arranged for a medical air transport. After
      eliminating other possibilities, she was diagnosed with VEE, which was confirmed
      in the laboratory. Over the next week, her mental status improved back to her
      normal neurologic baseline. CONCLUSIONS: Venezuelan equine encephalitis is an
      acute viral disease that causes acute illness in equines and humans, with
      symptoms ranging from a mild, flu-like syndrome to encephalitis or death.
      Laboratory abnormalities are common and include elevated hepatic transaminases,
      lymphocytosis, eosinophilia, and thrombocytopenia. Treatment is supportive, and
      complete recovery is expected within several weeks in most patients.

PMID- 22472657
TI  - Acute onset altered mental status in a previously healthy teenager.
AB  - Evans syndrome is a rare disease characterized by autoimmune hemolytic anemia and
      thrombocytopenia. Its initial presentation with intracranial hemorrhage is rare.
      We report a case of a 12-year-old girl who presented to the emergency department
      with altered mental status secondary to an intracranial hemorrhage and later
      diagnosed to have Evans syndrome.

PMID- 22472658
TI  - Transcutaneous bilirubin measurement methods in neonates and its utility for
      emergency department use.
AB  - Transcutaneous bilirubin measurements correlate with serum bilirubin measurements
      in neonates. They permit rapid measurements but do not provide fractionation
      information. Background information of bilirubin measurements is reviewed. The
      role of transcutaneous bilirubin measurements in the emergency department is
      reviewed.

PMID- 22472660
TI  - Pediatric emergency medicine: legal briefs.

PMID- 22472661
TI  - Subungual wooden splinter visualized with bedside sonography.
AB  - Bedside ultrasound has become increasingly important as an adjunct to clinical
      diagnosis and procedures in the emergency department. It is only recently that
      this modality, which involves no ionizing radiation, has become incorporated into
      the pediatric emergency department. We report a case of a 10-year-old boy with a
      suspected subungual wooden foreign body. Bedside ultrasound was used to identify
      and characterize the foreign body before removal and then to evaluate for any
      residual foreign body after removal. A brief review of the technique is
      presented, including the use of a water bath to enhance visualization of the
      object and decrease the patient's discomfort. This case highlights the utility of
      ultrasound in detecting radiolucent soft tissue foreign bodies.

PMID- 22472662
TI  - Pediatric emergency medicine fellowship programs.

PMID- 22472663
TI  - ECGs in the ED.

PMID- 22472664
TI  - New copyright transfer and conflict-of-interest process for all authors.

PMID- 22472666
TI  - Remembering scope of practice.

PMID- 22472665
TI  - IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II
      after bacterial re-stimulation of tolerized dendritic cells.
AB  - BACKGROUND: As essential components of the innate immune system, dendritic cells
      (DCs) can interact directly with pathogens as well as participate in the adaptive
      immune response. In cells closely related to DCs such as macrophages and
      monocytes, prior exposure to minute amounts of endotoxin can lead to a refractory
      period where subsequent exposure to higher doses fails to induce an inflammatory
      response; little research has investigated this effect on DCs. This study tested
      if murine bone marrow-derived dendritic cells (BM-DCs) respond to endotoxin- and
      bacterial sonicate-induced tolerance by decreased inflammatory and increased anti
      inflammatory response, and the role of IRAK-M, an intracellular negative
      regulator of TLR signaling, in this tolerance. RESULTS: Tolerized BM-DCs
      exhibited a significant drop in TNF-alpha and IL-12p70 production and increased
      IL-10 expression compared to untolerized cells. BM-DCs also showed the ability to
      develop heterotolerance, in which the LPS exposure alone was able to induce
      tolerance to Helicobacter pylori sonicate and TLR2 agonist Pam3Cys. Furthermore,
      the expression of IRAK-M was increased after restimulation of tolerized BM-DCs as
      determined qPCR and Western blot. IRAK-M exhibited a suppressive effect on
      surface expression of major histocompatibilty complex class II (MHC II) and CD80
      in LPS-tolerized BM-DCs. IL-10 expression in bacterial sonicate-tolerized IRAK-M
      /- BM-DCs was altered as compared to wild type BM-DCs, with tolerance-induced
      expression of IL-10 mitigated in tolerized IRAK-M-/- BM-DCs. CONCLUSION: Along
      with endotoxin, bacterial sonicate is able to induce refractory tolerance in BM
      DCs, and IRAK-M plays a role in modulating cell surface expression of MHC class
      II and CD80 and release of IL-10 during this tolerance.

PMID- 22472667
TI  - The effect of biofeedback training on patients with functional constipation.
AB  - The aim of this prospective quasi-experimental study was to explore the influence
      of biofeedback training on patients with functional constipation (FC). Changes in
      clinical symptoms, psychological status, quality of life, and autonomic nervous
      function in 21 FC patients before and after biofeedback training were
      investigated. The psychological status and quality of life were evaluated with
      the Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale
      (SDS), and a Chinese version of the MOS 36-Item Short-Form Health Survey.
      Autonomic nervous function was assessed on the basis of heart rate variability
      recorded with a HANS-1000 autonomic nervous biofeedback apparatus. After a
      complete course of training (10 sessions), clinical symptoms were greatly
      improved (p < .01), and the SAS and SDS scores were markedly decreased. There was
      a significant difference in the SAS and SDS scores before and after biofeedback
      (p < .01). The scores of general health perceptions, physical functioning,
      emotional role functioning, bodily pain, and vitality were increased
      significantly (p < .05), especially the scores of general health perceptions and
      emotional role functioning (p < .01), which indicated that quality of life in FC
      patients was significantly improved. No marked improvement of autonomic nervous
      function was found. Although a slight improvement in autonomic nervous activity
      was found, there was no significant statistical findings (p > .05). We conclude
      that biofeedback training can improve clinical symptoms, psychological status,
      and quality of life in FC patients, but further research is needed to determine
      whether biofeedback training can improve the autonomic nervous function in FC
      patients.

PMID- 22472668
TI  - Disparities in colorectal cancer screening behaviors: implications for African
      American men.
AB  - Guidelines published by the American College of Gastroenterologists suggest that
      African Americans (AA) begin preventive screening at the age of 45 years due to
      increased risk of colorectal cancer. This study examines characteristics
      associated with having fecal occult blood tests (FOBT), sigmoidoscopy, and
      colonoscopy among adults aged 45-75 years. Using cross-sectional data from the
      2007 Health Information National Trends Survey, the sample included 3,725
      participants (mean age = 59.01 +/- 8.41), with 59.8% female, 88.8% Caucasian, and
      11.2% AA. Binary logistic regression with interactions between race, gender, and
      age entered in block 2 revealed that odds of having FOBT, colonoscopy, or
      sigmoidoscopy were increased among older individuals with higher education. Fecal
      occult blood test was higher among women and those with insurance. Colonoscopy
      was higher among those with insurance and higher income. Having a sigmoidoscopy
      was more likely among those with higher income but was lower among AA men.
      Understanding the characteristics of individuals who participate in colorectal
      cancer screenings may contribute to the development of interventions geared
      toward those who do not, particularly AA men who are at greatest risk for
      colorectal morbidity and mortality.

PMID- 22472669
TI  - An observational study of family caregivers' quality of life caring for patients
      with a stoma.
AB  - The management of stomas following surgical resection often falls to family
      caregivers. The purpose of this observational survey was to investigate the
      family caregivers' quality of life caring for a patient with ostomy. Between
      August 2008 and July 2009, 144 eligible Italian family members caring for a
      patient with ostomy were evaluated using two questionnaires: the Caregiver
      Quality of Life Cancer survey and the Caregiver Burden Inventory. Both
      questionnaires have similar capabilities to explore the burden of caregiving. The
      Caregiver Quality of Life Cancer reported a total Quality of Life score of 97.11
      (SD = 14.36), whereas the Caregiver Burden Inventory score for the sample was
      51.95 (SD = 10.72). Variables of interest included health, self-perception,
      nationality, society and territory in which the person lives, education, job,
      standard of living, house, family, relations with partner, and friendship. Only
      those who provided complete data (n = 123) were included in the analyses. Data
      show that generally the family caregiver is married (92%), female (97%), and aged
      55.15 years (SD = 16.5). The burden of assistance is higher in younger single
      caregivers, whereas those with children or who are aged have economic concerns.
      Loss of spirituality is reported in people aged 30-49 and 71-90 years. Family
      Caregivers' Quality of Life is poor. Further research is needed to determine the
      effectiveness of social and economic interventions to help family caregivers in
      the management of long-term assistance.

PMID- 22472670
TI  - Postoperative constipation risk assessment in Turkish orthopedic patients.
AB  - This descriptive, correlational study was conducted to describe constipation risk
      assessment and the affecting factors of constipation risk of patients who have
      undergone major orthopedic surgery. Data were collected using a patient
      information form and the Constipation Risk Assessment Scale (CRAS) on the second
      postoperative day. Data were analyzed using the SPSS version 11.5 for Windows.
      The mean age of the 83 patients studied was 53.75 +/- 21.29 years. Subjects were
      hospitalized in the orthopedic wards for 14.39 +/- 15.17 days, and their current
      bowel habit was 2.18 +/- 1.80 stools per week. Of the sample, 63.9% were female,
      69.9% of the patients had a history of previous surgery, 45.8% had hip/knee
      arthroplasty surgery, and 55.4% had bowel problems during the hospitalization
      period. Patients had a medium risk for constipation according to the CRAS
      subscale (gender, mobility, and pharmacological agents). Total CRAS score was
      12.73 +/- 4.75 (medium risk) on the second postoperative day. In addition, age,
      marital status, educational level, having a history of surgery, and bowel
      elimination problems did have a significant effect on constipation risk. On the
      basis of the findings from this study, nurses must learn the postoperative
      constipation risk of orthopedic patients to implement safe and effective
      interventions.

PMID- 22472671
TI  - The effect of abdominal massage on gastric residual volume: a randomized
      controlled trial.
AB  - This study is a randomized controlled trial aimed at determining the effects of
      abdominal massage on high gastric residual volume seen in patients intermittently
      fed with enteral nutrition through a nasogastric tube. The study also
      investigated consequent abdominal distension and vomiting complications. The
      study was carried out in a university hospital between January and December 2009.
      The sample included 40 intervention (abdominal massage) and 40 control subjects.
      Findings demonstrated that 2.5% of the subjects in the massage group and 30.0% of
      the subjects in the control group developed high gastric residual volume from
      enteral nutrition through a nasogastric tube. Abdominal circumference
      measurements of subjects on the first and last days demonstrated that 20% of the
      subjects in the control group and only 2.5% of the subjects in the massage group
      developed abdominal distension (p = .044). Vomiting was observed in 10% of the
      control subjects; no vomiting was observed in the intervention group. Findings
      suggest that nurses should apply abdominal massage to subjects receiving enteral
      feedings intermittently to prevent high gastric residual volume and abdominal
      distension.

PMID- 22472672
TI  - Taenia saginata: failure treatment in a child with 5-year long-lasting infection.
AB  - The management of these infections requires protocols that allow the clinic and
      laboratory to reach a timely and accurate diagnosis through the differential
      identification of Taenia species and consequently determine appropriate
      treatment. On the other hand, the inadequate implementation of treatments and the
      lack of follow-up coupled with biological phenomena such as resistance to drugs
      contribute important risks of infection for the population. This case could be
      caused by a strain of T. saginata with a low sensitivity to albendazole. This
      case emphasizes the need of developing and implementing techniques that will help
      us differentiate the species of Taenia in laboratories as well as establish
      treatments with alternative drugs. It is important to report this kind of
      infection with the aim of giving laboratory personnel as well as healthcare
      providers a broader knowledge of these parasites in order to improve treatment
      with alternative drugs. In addition, improvements in the habits among individuals
      must be addressed to avoid the increased risk of infection.

PMID- 22472673
TI  - Famous endoscopy quotes.
AB  - These quotations, whether humorous or serious, provide insight into how
      gastroenterology nurses, gastroenterologists, and endoscopists feel about
      themselves as professionals, how other healthcare professionals perceive them,
      and their image in popular culture. Recognition of these aspects of
      gastroenterology nursing, gastroenterology, and endoscopy are important for self
      improvement, correcting public misperceptions, and appreciating how patient
      misperceptions about gastroenterology nurses and gastroenterologists and patient
      attitudes toward endoscopy may present barriers that gastroenterology
      professionals must overcome to improve patient care. These quotations also
      fulfill a need for witticisms during dry endoscopy lectures!

PMID- 22472674
TI  - Laughter: the best medicine or best measure?

PMID- 22472675
TI  - The Society of Gastroenterology Nurses and Associates has a new nurse fellowship
      program for evidence-based practice.

PMID- 22472676
TI  - A hazardous life - our role in injury prevention.
AB  - Having an active toddler has certainly made me far more aware of injuries, or
      more accurately, hazards with the potential for injury. Everyday situations and
      household objects suddenly become deathtraps and I find myself muddling along a
      line between being overly protective and overly relaxed. My approach varies
      according to some quasi-scientific factors such as 'probability of injury' and
      'severity of possible injury'. However, it also varies with 'convenience' factors
      such as 'in a hurry so bad timing for a fall right now' or 'she keeps climbing
      that so should let her fall while I'm here so she understands the danger'. The
      most injury prone times are when I'm multitasking, she's tired or other
      caregivers are present with no clear delineation of responsibility.

PMID- 22472677
TI  - Maxillofacial trauma.
AB  - BACKGROUND: Maxillofacial injuries are a common presentation to general practice
      and hospital emergency departments in Australia; surprisingly they can be easily
      overlooked at initial assessment. OBJECTIVE: This article describes the common
      typical clinical and radiographic findings in maxillofacial injuries that require
      further specialist treatment. Signs and symptoms requiring immediate treatment
      are highlighted and discussed individually. DISCUSSION: The full extent of
      functional disturbances might not be detectable in the first instance. Overlooked
      injuries may result in severe and enduring impairment of the patient and can have
      medicolegal ramifications.

PMID- 22472678
TI  - Meniscal tear - presentation, diagnosis and management.
AB  - BACKGROUND: Medial and lateral knee joint menisci serve to transfer load and
      absorb shock, aid joint stability and provide lubrication. The meniscus is the
      most commonly injured structure in the knee joint. Imaging techniques such as
      magnetic resonance imaging may be warranted but are no substitute for thorough
      clinical history and examination. OBJECTIVE: This article outlines the aetiology,
      presentation, diagnosis (both clinical and radiographic) and management of these
      important injuries. DISCUSSION: Magnetic resonance imaging can confirm clinical
      concern for meniscal tear, review intra- and extra-articular anatomical
      structures and exclude alternative diagnoses. Meniscal tears can be assessed
      arthroscopically for stability and vascularity. Even partial meniscectomy may
      lead to osteoarthritis. On the basis of the findings, treatment can be considered
      in terms of four Rs: Rest and Rehabilitate the patient (with physiotherapy), and
      if the patient is not improving on Review, Refer to an orthopaedic surgeon. New
      experimental surgical techniques seek to replace damaged tissue. These include
      meniscal allograft transplantation, biosynthetic scaffolds, growth factor and
      gene therapy, or a combination of these.

PMID- 22472679
TI  - Cervical spine - assessment following trauma.
AB  - BACKGROUND: Although cervical spine trauma is more common following high velocity
      mechanisms of injury resulting in multiple injuries, falls and low velocity
      mechanisms may also result in serious cervical spine injury. OBJECTIVE: This
      article describes the assessment and management of potential cervical spine
      injury in the primary care setting. DISCUSSION: Patients presenting following
      trauma should be assessed for risk of cervical spine injury according to one of
      two evidence based decision rules. If the nominated decision rule indicates high
      risk of injury, cervical spine imaging is indicated. An accurate history,
      physical examination and radiographic screening are required, preferably with
      computed tomography imaging, or five-view plain X-ray if computed tomography is
      unavailable. Magnetic resonance imaging should be considered in patients with
      neurologic symptoms or advanced cervical degenerative disease, as these patients
      are at particular risk of acute disc and ligamentous injury following trauma.

PMID- 22472680
TI  - Hands, fingers, thumbs - assessment and management of common hand injuries in
      general practice.
AB  - BACKGROUND: Hand injuries are a common presentation to general practice and
      optimal hand function is essential for good quality of life. OBJECTIVE: This
      article outlines an approach to the initial assessment of hand injuries, explains
      the principles of management and provides an overview of common hand injuries.
      DISCUSSION: While many injuries will heal remarkably well with minimal
      intervention, some injuries can result in permanent disability if not treated
      appropriately. The resulting negative impact on quality of life can be
      significant. An understanding of the principles that are unique to the management
      of hand injuries, such as reduced periods of immobilisation and the invaluable
      role of hand therapists, will help ensure that optimal healing and function is
      achieved.

PMID- 22472681
TI  - Hepatitis B serology.
AB  - This article forms part of our 'Tests and results' series for 2012, which aims to
      provide information about common tests that general practitioners order
      regularly. It considers areas such as indications, what to tell the patient, what
      the test can and cannot tell you, and interpretation of results.

PMID- 22472682
TI  - Shoulder injuries - management in general practice.
AB  - BACKGROUND: Shoulder injuries are common in the primary care setting, yet general
      practitioners may feel unequipped to confidently assess the patient presenting
      with shoulder pain. OBJECTIVE: This article provides a framework for the initial
      assessment of a patient presenting with an injured shoulder. DISCUSSION: A solid
      understanding of the anatomy and unique features of the shoulder is important to
      adequately assess any injury. A focused history needs to particularly explore the
      mechanism of injury, the type of dysfunction and the nature of the pain. On
      examination, particular attention should be paid to loss of symmetry,
      localisation of tenderness and the range of movement.

PMID- 22472683
TI  - Initial assessment of the injured shoulder.
AB  - BACKGROUND: Shoulder injuries are common in the primary care setting, yet general
      practitioners may feel unequipped to confidently assess the patient presenting
      with shoulder pain. OBJECTIVE: This article provides a framework for the initial
      assessment of a patient presenting with an injured shoulder. DISCUSSION: A solid
      understanding of the anatomy and unique features of the shoulder is important to
      adequately assess any injury. A focused history needs to particularly explore the
      mechanism of injury, the type of dysfunction and the nature of the pain. On
      examination, particular attention should be paid to loss of symmetry,
      localisation of tenderness and the range of movement.

PMID- 22472684
TI  - The Ottawa knee rules - a useful clinical decision tool.
AB  - BACKGROUND: Acute knee injuries are a common presentation in the primary care
      setting. The Ottawa knee rules provide guidance on how to identify which cases of
      knee injury require radiographic investigation. OBJECTIVE: This article describes
      the Ottawa knee rules and outlines their sensitivity, reproducibility and
      application in the clinical setting. DISCUSSION: The Ottawa knee rules are a
      valuable tool for clinicians in the routine management of acute knee injuries.
      Studies show that they are highly sensitive at identifying patients with
      fractures of the knee and have a high degree of interobserver agreement and
      reproducible results. Application of the Ottawa knee rules in appropriate
      clinical scenarios may reduce the number of unnecessary radiographs ordered,
      streamlining patient throughput and allowing for significant cost savings.
      Although designed for use in adults, some studies have suggested that the Ottawa
      knee rules may also be applicable to the paediatric population.

PMID- 22472685
TI  - Feeding in the first year of life - emerging benefits of introducing
      complementary solids from 4 months.
AB  - BACKGROUND: Current World Health Organization guidelines recommend exclusive
      breastfeeding for the first 6 months of life. Breastfeeding conveys clear
      benefits to both mother and child. These benefits are likely to be amplified by
      prolonged feeding. OBJECTIVE: This article outlines the emerging evidence that
      suggests possible benefits from introducing complementary solids from 4 months of
      age in developed countries. DISCUSSION: The human gut may have a critical early
      window during which it has an opportunity to develop immunological tolerance.
      Introducing complementary solids from 4 months of age may decrease the risk of
      food allergy and coeliac disease - immunological illnesses that have become a
      public health priority. The new draft National Health and Medical Research
      Council guidelines recommend introducing solids at around 6 months (22-26 weeks).
      However, given recent evidence, it may be appropriate to recommend the
      introduction of solids from 4 months of age in the Australian context.

PMID- 22472686
TI  - Dementia and driving - an approach for general practice.
AB  - BACKGROUND: As our population ages, the proportion of drivers with dementia will
      continue to rise. Increasingly, health professionals are faced with the clinical
      dilemma of determining fitness to drive. Unfortunately, the management of drivers
      with dementia is fraught with hazards. OBJECTIVE: This article attempts to
      provide an overview of the complex issue of driving and dementia as it relates to
      general practitioners in Australia. In addition, an evidence based management
      strategy is proposed. DISCUSSION: When determining an individual's fitness to
      drive, a clinician's input may have legal, ethical, emotional and social
      ramifications. At present, a clear consistent national protocol detailing how one
      should establish fitness to drive is lacking. There is a need for research
      addressing how to facilitate early retirement from driving without jeopardising
      patient-doctor relationships.

PMID- 22472687
TI  - Fitness to drive - GP perspectives of assessing older and functionally impaired
      patients.
AB  - BACKGROUND: General practitioners have expressed concern about their ability to
      assess patients' driving fitness. This study explores GP perspectives regarding
      assessing fitness to drive in older and functionally impaired patients. METHODS:
      We held face-to-face interviews with seven metropolitan GPs and a focus group
      with nine rural GPs. Data were analysed using thematic analysis. RESULTS: General
      practitioners were unsure whether they or driving authorities should have
      responsibility for assessing patients' fitness to drive; recognised that driving
      is important for maintaining independence; described referral to an occupational
      therapist as useful, and expressed concern about the lack of access to
      alternative forms of transport and also about privacy issues. Opinion was divided
      about the merits of the VicRoads Medical Report Form and the usefulness of the
      Austroads guide. DISCUSSION: This qualitative study suggests that some GPs may
      find assessing fitness to drive to be challenging and problematic in general
      practice. Further resources and education could assist these GPs to increase
      their confidence and competence in assessing a patient's fitness to drive.

PMID- 22472688
TI  - The Kirketon Road Centre - improving access to primary care for marginalised
      populations.
AB  - Marginalised populations, including at risk young people, injecting drug users
      and sex workers, are vulnerable to a range of preventable health related
      problems, yet they often have difficulty accessing mainstream primary healthcare
      services. The Kirketon Road Centre in Kings Cross, Sydney, has been providing
      accessible and acceptable primary healthcare to these populations for the past 25
      years. However, limited scientific evidence for the effectiveness of targeted
      primary healthcare services for this group of patients makes competing for scarce
      public health resources difficult. This article outlines some of the issues faced
      by these populations when accessing traditional health services and describes the
      work of the Kirketon Road Centre.

PMID- 22472689
TI  - Insights gained from symptom evaluation of esophageal motility disorders: a
      review of 4,215 patients.
AB  - BACKGROUND/AIMS: Achalasia (Ach), diffuse esophageal spasm (DES), nutcracker
      esophagus (NE), and nonspecific motility disorder (NSMD) are described primary
      esophageal body motility disorders; however, their clinical symptom correlation
      is poorly understood. The aim of this study is to examine the association between
      a patient's presenting symptoms and their manometric diagnosis. METHODS:
      Manometric findings and reported symptoms of all patients undergoing esophageal
      manometry at the Creighton University Medical Center were prospectively entered
      in a database. Twenty-four-year data from 1984 through 2008 were accessed and
      analyzed. RESULTS: Of the 4,215 patients, 130 (3.1%) had Ach, 192 (4.6%) had DES,
      290 (6.9%) had NE, 508 (12.1%) had NSMD, and 3,095 (73.4%) had normal esophageal
      body motility. There was significant symptom overlap between the groups. Ach and
      DES had a similar symptom distribution, with dysphagia being the predominant
      symptom. Patients with NE, normal body motility, and NSMD presented predominantly
      with reflux symptoms. There was an increasing prevalence of esophageal
      dysmotility (DES and NSMD) with age, and women were found to be more likely to
      have NE than men. CONCLUSION: In an individual, reported symptoms do not
      correlate with their manometric diagnosis in a predictable fashion, and a
      thorough physiological assessment should be obtained to understand and diagnose
      the disease process. Esophageal motility deteriorates with age.

PMID- 22472690
TI  - Alternative methods for H1 simulations in genome-wide association studies.
AB  - OBJECTIVE: Assessing the statistical power to detect susceptibility variants
      plays a critical role in genome-wide association (GWA) studies both from the
      prospective and retrospective point of view. Power is empirically estimated by
      simulating phenotypes under a disease model H1. For this purpose, the gold
      standard consists in simulating genotypes given the phenotypes (e.g. Hapgen). We
      introduce here an alternative approach for simulating phenotypes under H1 that
      does not require generating new genotypes for each simulation. METHODS: In order
      to simulate phenotypes with a fixed total number of cases and under a given
      disease model, we suggest 3 algorithms: (1) a simple rejection algorithm; (2) a
      numerical Markov chain Monte-Carlo (MCMC) approach, and (3) an exact and
      efficient backward sampling algorithm. In our study, we validated the 3
      algorithms both on a simulated dataset and by comparing them with Hapgen on a
      more realistic dataset. For an application, we then conducted a simulation study
      on a 1000 Genomes Project dataset consisting of 629 individuals (314 cases) and
      8,048 SNPs from chromosome X. We arbitrarily defined an additive disease model
      with two susceptibility SNPs and an epistatic effect. RESULTS: The 3 algorithms
      are consistent, but backward sampling is dramatically faster than the other two.
      Our approach also gives consistent results with Hapgen. Using our application
      data, we showed that our limited design requires a biological a priori to limit
      the investigated region. We also proved that epistatic effects can play a
      significant role even when simple marker statistics (e.g. trend) are used. We
      finally showed that the overall performance of a GWA study strongly depends on
      the prevalence of the disease: the larger the prevalence, the better the power.
      CONCLUSIONS: Our approach is a valid alternative to Hapgen-type methods; it is
      not only dramatically faster but has 2 main advantages: (1) there is no need for
      sophisticated genotype models (e.g. haplotype frequencies, or recombination
      rates), and (2) the choice of the disease model is completely unconstrained
      (number of SNPs involved, gene-environment interactions, hybrid genetic models,
      etc.). Our 3 algorithms are available in an R package called 'waffect' ('double-u
      affect', for weighted affectations).

PMID- 22472691
TI  - Nelumal A, the active principle from Ligularia nelumbifolia, is a novel farnesoid
      X receptor agonist.
AB  - A series of 29 oxyprenylated and azoprenylated phenylpropanoids were chemically
      synthesized and tested in transfected cultured HepG2 cells by means of the dual
      luciferase assay as farnesoid X receptor (FXR) agonists, using the endogenous
      ligand chenodeoxycholic acid (CDCA) as reference drug. Among the tested
      molecules, three compounds, namely auraptene, nelumol A, and nelumal A showed a
      potency comparable to the endogenous ligand, with the latter natural product
      having a level of activity slightly superior to CDCA. Nelumal A is thus of
      interest as a valuable potential novel lead compound in the search for FXR
      agonists.

PMID- 22472692
TI  - 5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase)
      inhibitors.
AB  - Based on a previously identified HCV replication (replicase) inhibitor 1, SAR
      efforts were conducted around the pyrimidine core to improve the potency and
      pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be
      the optimal substituent at the pyrimidine 5-position. Due to potential reactivity
      concern, the 4-chloro residue was replaced by a methyl group with some loss in
      potency and enhanced rat in vivo profile. Extensive investigations at the C-2
      position resulted in identification of compound 16 that demonstrated very good
      replicon potency, selectivity and rodent plasma/target organ concentration.
      Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in
      dogs, while monkey exposure was rather low. Chemistry optimization towards a
      practical route to install the benzothiazole moiety resulted in an efficient
      direct C-H arylation protocol.

PMID- 22472693
TI  - Discovery of a novel acetylcholinesterase inhibitor by structure-based virtual
      screening techniques.
AB  - Acetylcholinesterase (AChE) is considered to be one of the most important targets
      for the treatment of Alzheimer's disease (AD). Previously our group has reported
      a series of tacrine-based hybrids as potent AChE inhibitors (AChEI). To discover
      more novel scaffolds, molecular docking and dynamics stimulation were applied to
      acquire the binding models of AChE with the most prominent compounds from our
      work. A structure-based pharmacophore model plus shape constraints was generated
      from the binding models and it was then employed to virtually screen commercial
      databases, giving a focused hit list of candidates. Subsequently, we scored the
      hit compounds by their molecular binding energies, which were calculated by
      MM/PBSA method. Fifteen compounds were selected and purchased for testing their
      anti-AChE effects, while seven of them showed inhibitory effects with IC(50)
      values ranging from 1.5 to 9.8 MUM. The drug-like properties of these compounds,
      including LogD, AlogP, molecular volume and Lipinski rule of five, were also
      calculated. Compounds 12 and 16 (IC(50)=2.5 and 1.5 MUM, respectively) exhibited
      potent activity and acceptable drug-like properties, thus might serve as leads
      for further modification. The data suggest that the presented model might be a
      valid approach for identification and development of new AChEIs.

PMID- 22472694
TI  - Discovery of 4'-azido-2'-deoxy-2'-C-methyl cytidine and prodrugs thereof: a
      potent inhibitor of Hepatitis C virus replication.
AB  - 4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the
      HCV NS5B RNA-dependent RNA polymerase, displaying an EC(50) value of 1.2 MUM and
      showing moderate in vivo bioavailability in rat (F=14%). Here we describe the
      synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and
      prodrug derivatives thereof.

PMID- 22472695
TI  - Pancreatic remnant reconstruction following pancreaticoduodenectomy and the
      pancreatic stump-closed pancreaticojejunostomy.

PMID- 22472696
TI  - An in vitro model of warm hypoxia-reoxygenation injury in human liver endothelial
      cells.
AB  - BACKGROUND: Ischemia-reperfusion or hypoxia-reoxygenation (H-R) injury adversely
      affects hepatic function following transplantation and major resection; the death
      of human sinusoidal endothelial cells (SECs) by apoptosis may play a central role
      in this process. Caspase-3 is an important intracellular protease in the
      intrinsic and extrinsic pathways of apoptosis. MATERIALS AND METHODS: SECs and
      EAhy926 cells were exposed to warm hypoxia at 37 degrees C, followed by
      reoxygenation at 37 degrees C. Activity of caspase-3 was quantified using Western
      blotting and colorimetric kinase assays. RESULTS: H-R caused a significant
      increase in caspase-3 activity compared with controls in both cell types.
      CONCLUSIONS: Warm H-R injury causes apoptotic cell death of SECs and immortalized
      cells, but with differing patterns of caspase activity.

PMID- 22472697
TI  - Comparison of open live donor nephrectomy, laparoscopic live donor nephrectomy,
      and hand-assisted live donor nephrectomy: a cost-minimization analysis.
AB  - BACKGROUND: Live donor kidney transplantation is the treatment of choice for end
      stage renal disease. Open donor nephrectomy (ODN) was the standard until the
      introduction of the laparoscopic donor nephrectomy (LDN) in 1995. Hand-assisted
      laparoscopic donor nephrectomy (HALDN) was added shortly thereafter. The
      laparoscopic techniques are associated with increased operating room times and
      equipment costs; however, these techniques speed patient return to normal
      activity. The aim of this study is to evaluate the cost of these techniques.
      MATERIALS AND METHODS: A decision analysis model was developed to simulate
      outcomes for donors undergoing ODN, LDN, and HALDN. Outcomes were simulated from
      both the institutional perspective (IP) and the societal perspective (SP).
      Baseline values and ranges were determined from a systematic review of the
      literature. Sensitivity analyses were conducted to test model strength. RESULTS:
      From the IP, ODN is the least costly strategy with a cost of $11,000, while the
      cost is $15,200 for HALDN and $15,800 for LDN. From the SP, HALDN is the least
      costly strategy costing $27,800, while the cost for LDN is $29,000 and for ODN is
      $41,000. In sensitivity analysis, ODN only became the dominant strategy if the
      days till return to work exceeded 58 in the HALDN strategy. LDN and HALDN were
      nearly equivalent as the rate of open conversion of LDN approached zero.
      CONCLUSIONS: HALDN is the least costly donor nephrectomy strategy, especially
      from the SP. The primary determinants of cost in this model are conversion to
      open and days till return to work.

PMID- 22472698
TI  - Limb ischemia-reperfusion differentially affects the periosteal and synovial
      microcirculation.
AB  - BACKGROUND: Joints are privileged compartments that enjoy increased protection
      against the inflammatory reactions affecting the extremities. We hypothesized
      that the functional characteristics of the microvasculature would contribute to
      the differential defensive potential of the synovial membrane. METHODS: We
      investigated the synovial microcirculatory reactions and compared them with those
      of the tibial periosteum in response to 60 min of total limb ischemia, followed
      by 180 min of ischemia-reperfusion (IR) in rats. Carrageenan/kaolin-induced knee
      monoarthritis, a neutrophil-driven synovial inflammation model, served as the
      positive control. RESULTS: IR brought about a significant reduction in red blood
      cell velocity in the capillaries and increases in rolling and adherence of the
      neutrophil leukocytes in the postcapillary venules (intravital microscopy), in
      adhesion molecule expression (intercellular adhesion molecule-1
      immunohistochemistry) and in xanthine oxidoreductase activity in the periosteum.
      These changes were also pronounced in carrageenan/kaolin-induced monoarthritis
      but were almost completely absent in the synovium after the IR challenge. Most
      importantly, even after IR and in carrageenan/kaolin monoarthritis, the synovial
      microcirculation was characterized by significantly greater red blood cell
      velocities than that in the periosteum under resting conditions. CONCLUSIONS: The
      ischemic duration, which significantly affected the functional integrity of the
      periosteal microcirculation, did not bring about a marked deterioration in that
      of the synovial membrane, suggesting that the synovial microcirculation is less
      endangered to the consequences of short-term tourniquet exposure than the
      periosteum. The greater microcirculatory red blood cell velocities and lower IR
      induced endothelial expression of intercellular adhesion molecule-1 in the
      synovial membrane might explain the greater resistance of this compartment to the
      inflammatory consequences of IR.

PMID- 22472699
TI  - [Anhydrotic ectodermal dysplasia associated to mannose-binding lectin
      deficiency].
AB  - Mannose-binding lectin (MBL) is a serum protein of the innate immune system. MBL
      enhances opsonophagocytosis by binding to carbohydrates expressed by multiple
      pathogens. MBL deficiency is due to polymorphisms in the structural and promoter
      sequences of the MBL2 gene and is associated with variety of recurrent
      infections, including respiratory tract infections. We present a case of
      anhidrotic ectodermal dysplasia associated with severe mannose-binding lectin
      deficiency, never described in patients with anhidrotic ectodermal dysplasia.

PMID- 22472700
TI  - Transplantation of human embryonic stem cell-derived pancreatic endoderm reveals
      a site-specific survival, growth, and differentiation.
AB  - Development of beta-cells from human embryonic stem cells (hESCs) could
      compensate for the shortage of islet donors required for diabetes therapy.
      Although pancreatic progenitors have been derived from hESCs using various
      protocols, no fully functional b-cells could be generated in vitro. We evaluated
      the in vivo growth and differentiation of PDX1+ pancreatic endoderm cells
      obtained from hESCs. Here we show site-specific survival and differentiation when
      comparing cells grafted in the epididymal fat pad or the subcutaneous space of
      NOD/SCID mice after 12 weeks follow-up. Subcutaneous grafts persisted and
      expressed PDX1 at all time points analyzed, showed PDX1 and NKX6.1 coexpression
      after 6 weeks, and contained NGN3+ cells after 12 weeks.These findings suggest
      that further specification along the pancreatic lineage occured at the
      subcutaneous site.In sharp contrast, in the fat pad grafts only a minority of
      PDX1+ cells remained after 2 weeks, and no further pancreatic differentiation was
      observed later on. In addition, contaminating mesenchymal cells present in the
      implants further developed into cartilage tissue after 6 weeks implantation in
      the fat pad, but not in the subcutaneous space. These findings indicate that the
      in vivo microenvironment plays a critical role in the further differentiation of
      transplanted pancreatic endoderm cells.

PMID- 22472701
TI  - Is cellular C4d a good biomarker for SLE nephritis?

PMID- 22472702
TI  - A 16 kb naturally occurring genomic deletion including mce and PPE genes in
      Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne's
      disease.
AB  - In this study we characterise the genomic and transcriptomic variability of a
      natural deletion strain of Mycobacterium avium subspecies paratuberculosis (MAP)
      prevalent in Spanish Guadarrama goats. Using a pan-genome microarray including
      MAP and M. avium subspecies hominissuis 104 genomes (MAPAC) we demonstrate the
      genotype to be MAP Type II with a single deletion of 19 contiguous ORFs (16 kb)
      including a complete mammalian cell entry (mce7_1) operon and adjacent proline
      glutamic acid (PE)/proline-proline-glutamic acid (PPE) genes. A deletion specific
      PCR test was developed and a subsequent screening identified four goat herds
      infected with the variant strain. Each was located in central Spain and showed
      epidemiological links suggestive of transmission between herds. A majority of
      animals infected with the variant manifested a paucibacillary form of the
      disease. Comparisons between virulent complete genome compliment strains isolated
      from multibacillary diseased goats and the MAP variant strain during entry into
      activated macrophages demonstrated an increased sensitivity in the variant to
      intracellular killing in human and ovine macrophages. As PPE and mce genes are
      associated with mycobacterial virulence and pathogenesis we investigated the
      interplay of these gene sets during cell entry using the MAPAC array. This showed
      significant differential transcriptome profiles compared to full genome
      complement MAP controls that included changes in other undeleted mce operons and
      PE/PPE genes, esx-like signalling operons and stress response/fatty acid
      metabolism pathways. This strain represents the first report of a MAP Type II
      genotype with significant natural genomic deletions which remains able to cause
      disease and is transmissible in goats.

PMID- 22472703
TI  - Evolutionary trend of foot-and-mouth disease virus in Hong Kong.
AB  - Foot-and-mouth disease is an endemic animal disease in Hong Kong. In this study,
      a total of 70 clinical specimens were collected from locally infected pigs from
      2001 to 2010. Phylogenetic analysis of VP1 sequences reveal that all Hong Kong
      FMDV serotype O isolates are classified into three lineages: HK-A and HK-B in
      Cathay topotype, and HK-C in SEA topotype. Regression analysis projects that the
      time of divergence from the most recent common ancestor of HK-A and HK-B are 1964
      +/- 12 and 1987 +/- 9 years respectively. Although HK-B shares a common ancestor
      with strains that caused outbreak in Taiwan and Philippines, there is no
      consolidated evidence demonstrating the order of introduction events among these
      regions. HK-C lineage is the latest FMDV isolated in Hong Kong. This virus is
      likely adopted from bovine into porcine. As local pigs confer immunity mainly
      against Cathay topotype viruses, introduction of HK-C viruses have led into an
      unexpectedly high severity and rapid spreading rate of the disease. A systematic
      surveillance and communication network is essential to provide accurate
      information in controlling the pandemics.

PMID- 22472704
TI  - Porcine reproductive and respiratory syndrome virus: antigenic and molecular
      diversity of British isolates and implications for diagnosis.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is an endemic disease of
      pigs, caused by PRRS virus, a member of the Arteriviridae family. First seen in
      Britain in 1991, the disease continues to be a significant economic and welfare
      problem for pig producers. To date, only PRRSV genotype 1 has been found in
      Britain. At the genetic level, a considerable increase has been reported in the
      diversity of PRRS viruses isolated in Britain between 2003 and 2007, versus the
      early 1990 s. In this study, the diversity has been shown to extend to the
      antigenic level too, with potential consequences for diagnostic methods.
      Antigenic diversity was assessed using a panel of twelve monoclonal antibodies,
      only one of which reacted with all isolates tested. Nine diverse viruses were
      compared as potential antigens in immunoperoxidase monolayer assays, where each
      one produced quite different results for a common panel of sera. As a single
      virus is used in each diagnostic assay, results must therefore be interpreted
      cautiously. For a real-time RT-PCR assay, published oligonucleotide primer and
      probe sequences were evaluated against available genetic sequences of British and
      European viruses, and were re-designed where considerable mismatches were found.
      The multiplex assay incorporating these modified primers to detect genotype 1 and
      2 PRRS viruses was then validated for use with diagnostic sera and tissues. As
      the increasing degree of diversity exhibited by British strains is mirrored in
      other countries, PRRSV will continue to provide an ongoing challenge to diagnosis
      at a global, as well as national level.

PMID- 22472705
TI  - Chromatin isolation by RNA purification (ChIRP).
AB  - Long noncoding RNAs are key regulators of chromatin states for important
      biological processes such as dosage compensation, imprinting, and developmental
      gene expression (1,2,3,4,5,6,7). The recent discovery of thousands of lncRNAs in
      association with specific chromatin modification complexes, such as Polycomb
      Repressive Complex 2 (PRC2) that mediates histone H3 lysine 27 trimethylation
      (H3K27me3), suggests broad roles for numerous lncRNAs in managing chromatin
      states in a gene-specific fashion (8,9). While some lncRNAs are thought to work
      in cis on neighboring genes, other lncRNAs work in trans to regulate distantly
      located genes. For instance, Drosophila lncRNAs roX1 and roX2 bind numerous
      regions on the X chromosome of male cells, and are critical for dosage
      compensation (10,11). However, the exact locations of their binding sites are not
      known at high resolution. Similarly, human lncRNA HOTAIR can affect PRC2
      occupancy on hundreds of genes genome-wide( 3,12,13), but how specificity is
      achieved is unclear. LncRNAs can also serve as modular scaffolds to recruit the
      assembly of multiple protein complexes. The classic trans-acting RNA scaffold is
      the TERC RNA that serves as the template and scaffold for the telomerase complex
      (14); HOTAIR can also serve as a scaffold for PRC2 and a H3K4 demethylase complex
      (13).    Prior studies mapping RNA occupancy at chromatin have revealed
      substantial insights (15,16), but only at a single gene locus at a time. The
      occupancy sites of most lncRNAs are not known, and the roles of lncRNAs in
      chromatin regulation have been mostly inferred from the indirect effects of
      lncRNA perturbation. Just as chromatin immunoprecipitation followed by microarray
      or deep sequencing (ChIP-chip or ChIP-seq, respectively) has greatly improved our
      understanding of protein-DNA interactions on a genomic scale, here we illustrate
      a recently published strategy to map long RNA occupancy genome-wide at high
      resolution (17). This method, Chromatin Isolation by RNA Purification (ChIRP)
      (Figure 1), is based on affinity capture of target lncRNA:chromatin complex by
      tiling antisense-oligos, which then generates a map of genomic binding sites at a
      resolution of several hundred bases with high sensitivity and low background.
      ChIRP is applicable to many lncRNAs because the design of affinity-probes is
      straightforward given the RNA sequence and requires no knowledge of the RNA's
      structure or functional domains.

PMID- 22472706
TI  - Fahr's disease with oral manifestations: report of a rare case.
AB  - OBJECTIVE: The purpose of this article is to discuss the general and oral
      findings in a patient with Fahr's disease, an uncommon disorder. CLINICAL
      PRESENTATION AND INTERVENTION: A patient presented with the complaint of partial
      anodontia, but further clinical and radiographic investigations showed a myriad
      of findings including stunted growth, osteoporosis and pathological
      calcifications. Oral findings included oligodontia and advanced periodontitis in
      relation to the present teeth. Full-mouth rehabilitation was eventually planned
      for the patient. CONCLUSION: This case shows the necessity for dentists to be
      aware of symptoms associated with Fahr's syndrome in order to make appropriate
      referrals and to enable diagnosis and treatment.

PMID- 22472707
TI  - Voluntary changes in step width and step length during human walking affect
      dynamic margins of stability.
AB  - "Cautious" gait is generally characterized by wider and shorter steps. However,
      we do not clearly understand the relationship between step characteristics and
      individuals' stability. Here, we examined the effects of voluntarily altering
      step width (SW) and step length (SL) on individuals' margins of stability.
      Fourteen participants completed three 3-min treadmill walking trials during three
      SL (short, normal with metronome, and long) and three SW (narrow, normal and
      wide) manipulation conditions. SL manipulations yielded significant changes in
      mean anterior-posterior (AP) margins of stability (MOS(ap)) (p<0.0005) but not
      mediolateral (ML) margins of stability (MOS(ml)) (p>=0.0579). Taking wider steps
      increased mean MOS(ml) while decreasing MOS(ap) (p<0.0005). Walking with either
      wider or long steps, each of which increases the base of support, yielded
      increased AP and ML MOS variability (p<=0.0468). Step-to-step analysis of MOS(ml)
      indicated that subjects took stable steps followed immediately by stable steps.
      Overall, short-term, voluntary adoption of wider steps may help increase
      instantaneous lateral stability but shorter steps did not change lateral
      stability during unperturbed walking. We suggest that the observed changes in
      stability margins be considered in gait training programs which recommend short
      term changes in step characteristics to improve stability.

PMID- 22472708
TI  - Investment in primary care--is it worthwhile?

PMID- 22472709
TI  - New Zealand evidence for the impact of primary healthcare investment in Capital
      and Coast District Health Board.
AB  - AIMS: This paper provides New Zealand evidence on the effectiveness of primary
      care investment, measured through the Capital and Coast District Health Board's
      (DHB) Primary Health Care Framework. The Framework was developed in 2002/2003 to
      guide funding decisions at a DHB level, and to provide a transparent basis for
      evaluation of the implementation of the Primary Health Care Strategy in this
      district. METHODS: The Framework used a mixed method approach; analysis was based
      on quantitative and qualitative data. RESULTS AND CONCLUSIONS: This article
      demonstrates the link between investment in primary health care, increased access
      to primary care for high-need populations, workforce redistribution, and improved
      health outcomes. Over the study period, ambulatory sensitive hospitalisations and
      emergency department use reduced for enrolled populations and the District's
      immunisation coverage improved markedly. Funding and contracting which enhanced
      both 'mainstream' and 'niche' providers combined with community-based health
      initiatives resulted in a measurable impact on a range of health indicators and
      inequalities.  Maori primary care providers improved access for Maori but also
      for their enrolled populations of Pacific and Other ethnicity. Growth and
      redistribution of primary care workforce was observed, improving the availability
      of general practitioners, nurses, and community workers in poorer communities.

PMID- 22472710
TI  - Investigating factors that influence success of Pacific students in first-year
      health sciences at university in New Zealand.
AB  - AIMS: Pacific peoples in New Zealand are a migrant population and suffer
      disproportionately from poor education outcomes compared to the total population.
      The purpose of this study was to understand factors that influence academic
      achievement of Pacific students studying health sciences at the University of
      Otago. METHODS: Pacific students enrolled in health sciences first year (HSFY) in
      2010 were invited to complete a questionnaire on their experiences and adjustment
      to university. It sought information on university preparedness and "engagement
      factors". Academic results were obtained. RESULTS: 90% of eligible Pacific
      students completed the questionnaire. Most students scored their experiences at
      university highly. Following first semester exams, 60% passed all papers and 40%
      failed one or more papers. Of those who failed a paper, 50% felt they had
      developed good study skills. One-third would memorise facts without fully
      understanding them. Fourteen (23%) HSFY students were successful in getting into
      a health professional course after end-of-year exams. CONCLUSIONS: Factors
      influencing academic outcomes of Pacific students at first year of study at
      University are complex. Further research focussing on effective roles
      universities can play in the provision of support, and the influence of
      preparedness prior to entering university is required.

PMID- 22472711
TI  - Final-year medical students' perceptions of maternity care in general practice.
AB  - AIMS: To investigate the perceptions of final year medical students' (known as
      trainee interns or TIs) at the University of Otago about maternity care in
      general practice, their possible future roles in general practice maternity care,
      and factors influencing this. METHODS: An anonymous questionnaire using the
      online programme SurveyMonkey was emailed to the 227 Otago University TIs.
      Results were analysed using SurveyMonkey statistical analysis. RESULTS: The
      response rate was 50.7%. About 90% of the TIs thought GPs should provide
      antenatal and postnatal care, 80.7% supported shared care and 55.7% thought GPs
      should provide full maternity care if interested and trained to do so. Almost 80%
      thought women should have access to full maternity care in general practice.  If
      practicing as a GP 90% or more of respondents would consider providing prenatal,
      early pregnancy, antenatal, postnatal care, or shared care and 64.0% full
      maternity care. Of the 29 TIs (25.2%) who had seen a GP practicing full maternity
      care 82.8% would consider offering this level of care if practicing as a GP. And
      68.3% of the 65 TIs interested in a rural general practice career would consider
      providing full maternity care. Issues of training, professional support, funding
      and continuity of care for patients were important factors in contemplating
      providing full maternity care. CONCLUSIONS: TIs are interested in providing a
      wide range of maternity services if practicing as a GP. Many professional and
      lifestyle issues could influence our future doctors when deciding whether to
      practice maternity care in general practice.

PMID- 22472712
TI  - A survey of personal digital assistant use in a sample of New Zealand doctors.
AB  - AIM: To gather information about handheld computing hardware and software usage
      by hospital based doctors in New Zealand (NZ). METHOD: An online tool
      (SurveyMonkey) was used to conduct the survey from 27 June to 10 September 2010.
      Distribution of the survey was via an email to all NZ District Health Boards
      (DHBs). RESULTS: There were 850 responses. About half of respondents (52%) used a
      personal digital assistant (PDA), 90% using it at least once daily. Usage varied
      greatly between DHBs (27-100%), perhaps related to institutional support. Among
      PDA users, the most common applications were the non-clinical; Scheduler (95%),
      Contacts (97%), and Tasks (83%). Users felt PDAs helped considerably with
      organisation and time saving. For non-users there were a range of barriers to
      usage, cost being a large factor. Another major barrier identified by both users
      and non-users was lack of organisational integration and support. CONCLUSIONS:
      Half of survey respondents used a PDA. PDA usage of responders from different
      DHBs varied considerably. Perceived barriers to PDA use included cost and lack of
      institutional support. A collaborative approach between clinical leadership and
      Information Technology teams to address barriers may result in increased utility
      and usage of PDAs in the NZ health system.

PMID- 22472713
TI  - Binge drinking and alcohol-related behaviours amongst Pacific youth: a national
      survey of secondary school students.
AB  - AIM: Previous studies show Pacific youth polarised as either non/occasional
      drinkers or heavy binge drinkers. The aim of this study is to describe the
      demographic, cultural, home and neighbourhood environments of the two types of
      Pacific drinkers (non-binge drinkers and binge drinkers) to develop risk and
      protective profiles for alcohol related behaviours. METHODS: Data were collected
      as part of Youth'07, a nationally representative survey of the health and well
      being of New Zealand youth. 1,190 Pacific students who identified any of their
      ethnicities as Samoan, Cook Islands, Tongan, Niue, Tokelauan, Fijian, or Other
      Pacific Peoples were included. RESULTS: Data was available on 974 students of
      whom 31.6% were binge drinkers. Students who were younger and had parental
      Pacific language use at home were less likely to binge drink than other students.
      Parents' knowledge of young people's activities after school and at night time
      was also protective of binge drinking, while participating in sports teams or a
      sports club was associated with increased risk of binge drinking. CONCLUSION:
      This study indicates the transnational nature of Pacific communities in New
      Zealand who bring and maintain traditional cultural practices which seem health
      protective. While participation in sports activities may have health benefits,
      our findings indicate the need for a more proactive approach on the part of
      policymakers and the sporting sector to address the associated risk of binge
      drinking. Alcohol interventions that de-normalise alcohol overconsumption are
      warranted for young Pacific New Zealanders.

PMID- 22472714
TI  - Every child to thrive, belong and achieve? Time to reflect and act in New
      Zealand.
AB  - New Zealand continues to grapple with poor and inequitable child health and
      wellbeing outcomes. The associated high economic costs, the long-term impact on
      adult health and New Zealand's international children's rights obligations
      provide further grounds for action. Although there have been many different
      reports offering solutions and some key areas of progress, gains have been
      limited and there has not been sufficient clarity and agreement on wider actions.
      The environment is complex and solutions cross agency and disciplinary
      boundaries. This paper reviews the current situation and proposes a set of
      actions to improve child health and equity. These include a group of
      recommendations on high-level leadership and coordination, actions to address
      social conditions, and a range of specific health and wellbeing actions. Progress
      will require the will, commitment and courage of many to acknowledge the issues
      and find a way forward.  Preventing suffering and ensuring the wellbeing of our
      youngest citizens during their formative years is an ethical issue for our
      nation, an issue of what we value as a society, and the best investment for a
      highly productive, innovative and resilient nation for the future.

PMID- 22472715
TI  - Options for postgraduate anatomy education in Australia and New Zealand.
AB  - AIMS: Medical education in Australia has changed considerably in recent times. As
      a result, hours dedicated to subjects such as anatomy have been reduced. Young
      doctors preparing for a career in anatomy-focussed specialties such as surgery
      and radiology require an indepth knowledge of this subject matter. Many
      Australian and New Zealand universities now offer postgraduate anatomy courses to
      address this potential gap in a budding surgeon's education. This article
      summarises the current options for postgraduate surgical anatomy education in
      Australia and New Zealand. METHODS: All universities in Australia and New Zealand
      were contacted between September 2010 and December 2010 regarding the nature and
      content of course offerings. An Internet-based search was also conducted.
      RESULTS: There are currently nine universities in Australia and New Zealand
      offering postgraduate anatomy courses. Courses vary in contact hours, dissection
      time, lecture content, and examination methods. There are currently two
      universities offering a Postgraduate Diploma of Surgical Anatomy - the University
      of Melbourne, and the University of Otago. University of Western Australia and
      the University of New England offer a graduate diploma and a graduate
      certificate, respectively. Several other universities offer courses that deliver
      quality anatomical education but do not award students a university-recognised
      qualification. The Australian Orthopaedic Association now offers courses in
      Perth, Sydney and Brisbane, which delivers anatomy education specific to
      orthopaedics. CONCLUSIONS: There are a number of courses available to budding
      surgeons and radiologists to help fill the anatomy education void. With the
      development of such courses questions of accessibility, affordability and equity
      remain.

PMID- 22472716
TI  - Medical students performing lumbar punctures: are we doing enough?
AB  - It is safe to suggest that every medical student in their clinical years (and
      certainly every doctor) should be able to act alone in emergency situations and
      with limited resources. This includes supporting life functions, performing
      diagnostic procedures, establishing a clinical diagnosis, and/or initiating
      treatment. However, medical school curricula do not always cater for such
      demands. Lumbar puncture is a basic procedure performed routinely in emergency
      departments, neurology wards and elsewhere in hospitals. Medical students,
      however, do not usually get the chance to perform lumbar punctures during their
      basic training. In fact, Australian and New Zealand medical students seem to get
      the least exposure when compared to other students in other developed countries.
      This article examines the current status of medical students performing lumbar
      punctures around the world, and the ethical considerations around this issue.

PMID- 22472717
TI  - Modelling empathy in medical and nursing education.
AB  - Medical and nursing student numbers are expected to increase significantly in NZ
      over the next few years. The ethical, and professional and clinical skills'
      training of trainee health practitioners is a central and crucial component in
      medical and nursing education and is underpinned by a strong commitment to
      improve patient health and well being. In this discussion we reflect on the
      virtue of empathy and the importance of role modelling in the education of nurses
      and doctors. We endorse the claim that as medical educators, how and what we
      teach matters.

PMID- 22472718
TI  - Sildenafil: a novel therapy in the management of cardiac syndrome X.

PMID- 22472719
TI  - Medical image. Macrodystrophia lipomatosa: multidetector CT and MRI findings.

PMID- 22472720
TI  - Medical image. A rare but fatal complication of end stage renal disease: calcific
      uremic arteriolopathy.

PMID- 22472721
TI  - Medical image. Coughing: think about long-standing bronchial foreign body:
      foreign body aspiration (FBA).

PMID- 22472723
TI  - T cell epitopes of the timothy grass pollen allergen Phl p 5 of mice and men and
      the detection of allergen-specific T cells using Class II Ultimers.
AB  - BACKGROUND: Knowledge of allergen-specific T cell epitopes is a prerequisite not
      only for therapeutic approaches but also for elucidating immunological mechanisms
      of type I allergy. Ex vivo detection of allergen-specific T cells using class II
      tetramer technology has become an important tool for investigating immune
      responses in atopic and healthy individuals. METHODS: Using (3)H-thymidine
      incorporation assays, T cell epitopes specific for the major timothy grass pollen
      allergen Phl p 5.0101 were mapped in 11 allergic donors and two different mouse
      strains. Different protocols for expansion/restimulation of T cells from the
      blood of allergic donors and detection of allergen-specific T cells by Class II
      Ultimer staining were evaluated. RESULTS: We identified several new Phl p 5.0101
      class II T cell epitopes in allergic patients and confirmed previously published
      ones. Additionally, we discovered the major T cell epitopes in BALB/c and C57BL/6
      mice. Using a novel Class II Ultimer, we detected epitope-specific T cells
      expanded from the blood of an allergic donor. CONCLUSIONS: Epitope mapping of Phl
      p 5.0101 revealed an immunodominant epitope in BALB/c and C57BL/6 mice and an
      immunodominant region in humans (amino acids 259-282), which was recognized by 8
      out of 11 allergic donors. Detection of Phl p 5-specific T cells was demonstrated
      using a Class II Ultimer specific for epitope 196-210. Successful detection of
      ultimer-positive T cells was strongly dependent on a resting phase after in vitro
      expansion.

PMID- 22472724
TI  - Asthma and bronchodilator responsiveness are associated with polymorphic markers
      of ARG1, CRHR2 and chromosome 17q21.
AB  - OBJECTIVE: Asthma is caused by complex interactions between multiple genes. beta2
      Agonist is the standard rescue treatment to relieve asthma symptoms and
      bronchoconstriction. A genetic study for spirometric parameters helps to predict
      the responses to this antiasthma treatment. This study investigated the
      relationship between asthma and bronchodilator responsiveness (BDR) and eight
      asthma genes. METHODS: Fifteen single-nucleotide polymorphisms in these genes
      were genotyped in 345 Chinese asthmatics and 464 controls. Gene-gene interactions
      were analysed by generalized multifactor dimensionality reduction (GMDR).
      RESULTS: The diagnosis of asthma was associated with rs7216389 in ORMDL3 [odds
      ratio (OR) 0.74 and 95% confidence interval (95% CI) 0.56-0.99] and rs3756780 in
      ARG1 (OR 0.67, 95% CI 0.51-0.89) and BDR with rs2749935 in ARG1. However, none of
      these associations remained significant at 5% when adjusted for multiple testing
      by the Bonferroni correction or a false discovery rate. GMDR analyses revealed
      that rs7216389 in ORMDL3 and rs3756780 in ARG1 might interact for a risk of
      asthma. Individuals with high-risk genotypes had OR 1.66 (95% CI 1.24-2.23) for
      asthma when compared with those with low-risk genotypes. GMDR suggested a two
      locus model with rs2749935 in ARG1 and rs2190242 in CRHR2 to be associated with
      BDR. Specifically, reversibility of forced expiratory volume in 1 s was higher in
      high-risk than that in low-risk patients [mean (95% CI): 10.7 (8.6-12.9) vs. 6.8
      (5.9-7.6)%]; with the latter group showing higher forced expiratory volume in 1 s
      reversibility compared with high-risk controls [2.8 (1.4-4.3)%]. CONCLUSION: ARG1
      and ORMDL3 may interact to determine the risk of asthma and ARG1 and CRHR2 to
      alter BDR in asthmatics. Nonetheless, this study is only hypothesis-generating as
      none of the single marker comparisons is significant when adjusted for multiple
      testing. These findings need to be confirmed in independent populations.

PMID- 22472725
TI  - Effect of 710-nm visible light irradiation on neuroprotection and immune function
      after stroke.
AB  - OBJECTIVE: The phototherapeutic effects of low level infrared laser irradiation
      (808 nm) on brain neuronal cell protection after stroke have been presented
      recently. We previously reported that 710-nm wavelength visible light (VIS)
      increases total lymphocyte counts in vivo, especially CD4(+) T lymphocytes. In
      this study, we investigated the effects of 710-nm VIS irradiation on neuronal
      protection and recovery correlating with cellular immunity in stroke rats.
      METHODS: Rats were subjected to 90-min middle cerebral artery occlusion (MCAO)
      followed by reperfusion and were divided into two groups: irradiation and no
      irradiation. The irradiation group had been exposed to 710-nm VIS for 3 weeks
      after MCAO establishment or sham operation. The helper T cell (CD4(+)) count in
      the whole blood and infarct volume were measured. Messenger RNA expression levels
      of IL-4 and IL-10 in peripheral blood mononuclear cells were measured, a
      histologic study including microglia activation and regulatory T (Treg) cell
      markers, neurological severity scoring and a parallel bar walking test were all
      performed. RESULTS: CD4(+) cell count was reduced after MCAO but was
      significantly increased by 710-nm VIS irradiation. The infarct sizes were
      decreased in the MCAO + irradiation group compared with the MCAO control group.
      IL-10 mRNA expression and the immunoreactivity of Treg cells were increased in
      the MCAO + irradiation group compared with the MCAO control group. Increased
      microglia activation after MCAO was reduced by 710-nm VIS irradiation. The
      irradiation group also showed improved neurological severity score levels and
      step fault scores after MCAO. CONCLUSIONS: Our data suggest that 710-nm VIS
      irradiation may activate cellular immunity, reduce brain infarction and
      ultimately induce functional recovery in a stroke animal model.

PMID- 22472726
TI  - Neuroprotection in vascular dementia: a future path.
AB  - The burden of cognitive disorders is likely to increase over the coming years due
      to both increased longevity and altered risk factor patterns, arising from
      changes in lifestyle, healthcare and society. Vascular dementia with its
      underlying heterogeneous pathology, is a challenge for clinicians, and is
      frequently further aggravated by overlap with other neurodegenerative processes.
      Current Alzheimer's disease drugs have had limited clinical efficacy in treating
      vascular dementia and none have been approved by major regulatory authorities
      specifically for this disease. Moving forward, a valid choice may be a multimodal
      therapy, as has already been successfully proven in Alzheimer's disease.
      Actovegin, a hemodialysate derived from calf blood, has been shown to have
      effects on a variety of cellular processes and a recent experimental study has
      revealed its neuroprotective mechanisms of action. These data, coupled with
      positive results from clinical trials in mixed dementia populations, have served
      as a foundation for the design of a new trial investigating the efficacy and
      disease-modifying effects of Actovegin in post-stroke cognitive impairment.

PMID- 22472727
TI  - Environmental biomechanics substantiated by defined pillar micropatterns govern
      behavior of human mesenchymal stem cells.
AB  - While evidence on the impact of the biomechanical environment elasticity on human
      mesenchymal stem cell (hMSC) behavior is growing, the aspect of micropatterning
      is still poorly understood. Thus, the present study aimed at investigating the
      influence of defined environmental micropatterning on hMSC behavior. Following
      characterization, hMSCs were grown on defined pillar micropatterns of 5, 7, 9,
      and 11 um. With respect to cell behavior, primary hMSC adhesion was detected by
      indirect immunofluorescence (iIF) for paxillin, vinculin, integrin alphaV, and
      actin, while proliferation was visualized by histone H3. Morphogenesis was
      monitored by scanning electron microscopy and the expression of stem cell
      specific biomarkers by real-time PCR. Favoritism of primary adhesion of hMSCs on
      pillar tops occurred at smaller pillar micropatterns, concomitant with cell
      flattening. While vinculin, integrin alphaV, and paxillin appeared initially more
      cytoplasmic, high pillar micropatterns favored a progressive redistribution with
      polarization to cell tension sites and at cell borders. Accomplishment of
      morphogenesis at day 3 revealed establishment of fully rotund cell somata at 5
      um, while hMSCs appeared progressively elongated at rising micropatterns. The
      hMSC proliferation capacity was influenced by pillar micropatterns and gene
      expression analysis of stem cell- and differentiation-associated biomarkers
      disclosed clear modulation by distinct pillar micropatterns. In response to
      environmental biomechanics, our results show that hMSC behavior is governed by
      pillar micropatterning. In turn, these findings may form the basis to
      prospectively direct lineage specificity of hMSCs in a customized fashion.

PMID- 22472728
TI  - Improving physician clinical documentation quality: evaluating two self-efficacy
      based training programs.
AB  - BACKGROUND: Clinical documentation is critical to health care quality and cost.
      The generally poor quality of such documentation has been well recognized, yet
      medical students, residents, and physicians receive little or no training in it.
      When clinical documentation quality (CDQ) training for residents and/or
      physicians is provided, it excludes key constructs of self-efficacy: vicarious
      learning (e.g., peer demonstration) and mastery (i.e., practice). CDQ training
      that incorporates these key self-efficacy constructs is more resource intensive.
      If such training could be shown to be more effective at enhancing clinician
      performance, it would support the investment of the additional resources required
      by health care systems and residency training programs. PURPOSES: The aim of this
      study was to test the impact of CDQ training on clinician self-efficacy and
      performance and the relative efficacy of intervention designs employing two
      versus all four self-efficacy constructs. METHODOLOGY/APPROACH: Ninety-one
      internal medicine residents at a major academic medical center in the
      northeastern United States were assigned to one of two self-efficacy-based
      training groups or a control group, with CDQ and clinical documentation self
      efficacy measured before and after the interventions. A structural equation model
      (AMOS) allowed for testing the six hypotheses in the context of the whole study,
      and findings were cross-validated using traditional regression. FINDINGS:
      Although both interventions increased CDQ, the training designed to include all
      four self-efficacy constructs had a significantly greater impact on improving
      CDQ. It also increased self-efficacy. PRACTICE IMPLICATIONS: CDQ may be
      significantly improved and sustained by (a) training physicians in clinical
      documentation and (b) employing all four self-efficacy constructs in such
      training designs.

PMID- 22472729
TI  - Bipolar Disorder is a two-edged sword: a qualitative study to understand the
      positive edge.
AB  - BACKGROUND: Bipolar Disorder (BD) can have highly detrimental effects on the
      lives of people with the diagnosis and those who care about them. However,
      growing evidence suggests that aspects of bipolar experiences are also highly
      valued by some people. METHOD: We aimed to understand how participants with a
      diagnosis of BD made sense of what they took to be positive about their bipolar
      experiences. Interpretative Phenomenological Analysis was used in the collection
      and analysis of data from 10 individuals in the UK. RESULTS: Positive aspects
      were numerous, highly valued and participants welcomed the opportunity to discuss
      them. Three important themes emerged: 1) Direct positive impact of bipolar
      experiences on everyday life including amplification of internal states, enhanced
      abilities and more intense human connectedness; 2) Lucky to be bipolar - the
      sense of having been given a special gift; 3) Relationship between the self and
      bipolar experiences. Limitations Given the small size, further research is needed
      to explore how widely positive aspects of BD are experienced. CONCLUSIONS: These
      themes highlight the need to invite people to talk about the positive aspects of
      their bipolar experiences as well as the difficulties they face. This may help us
      to understand ambivalence to current treatment and to develop interventions that
      minimise the negative impacts, whilst recognising and potentially retaining some
      of the positives.

PMID- 22472730
TI  - Comparison of lactulose and glucose breath test for diagnosis of small intestinal
      bacterial overgrowth in patients with irritable bowel syndrome.
AB  - BACKGROUND AND AIMS: Validity of the lactulose breath test (LBT) to diagnose
      small intestinal bacterial overgrowth (SIBO) has been questioned. Therefore, a
      study was planned to compare LBT with glucose breath test (GBT) to diagnose SIBO
      in irritable bowel syndrome (IBS) patients and controls. METHODS: 175 diarrhea
      predominant IBS patients and 150 apparently healthy controls were enrolled. IBS
      was diagnosed according to Rome II criteria. Breath samples were collected every
      10 min up to 180 min. Breath H2 and CH4 were measured using an SC MicroLyzer.
      SIBO was positive with a sustained increase in breath H2 or CH4 or both >=10 ppm
      over a baseline value within <90 min in case of LBT and within <120 min in GBT.
      RESULTS: SIBO was positive in 60/175 (34.3%) patients by lactulose and in 11/175
      (6.2%) patients by GBT. In controls, LBT was positive for SIBO in 45/150 (30%)
      patients and in 1/150 (0.66%) patients by GBT. Positive LBT for SIBO was not
      significantly different in patients and controls; while using GBT, SIBO was
      significantly higher (p < 0.01) in patients as compared to controls. By using GBT
      as gold standard for SIBO, sensitivity, specificity, positive predictive value
      and negative predictive value of LBT in IBS patients was 63.6, 67.7, 11.7 and
      96.6% respectively. CONCLUSION: LBT is not a good test to discriminate SIBO in
      IBS patients from controls.

PMID- 22472731
TI  - Activation of c-Jun NH(2)-terminal kinase is required for porcine reproductive
      and respiratory syndrome virus-induced apoptosis but not for virus replication.
AB  - Apoptosis of host cells plays a critical role in pathogenesis of virus infection.
      MAPK kinases especially stress-activated protein kinases c-Jun NH(2)-terminal
      kinase (SAPK/JNK) and p38 are often involved in virus-mediated apoptosis. It has
      been shown that porcine reproductive and respiratory syndrome virus (PRRSV)
      infection resulted in apoptosis of the host cells both in vitro and in vivo. The
      current investigation was initiated to determine whether stress-activated protein
      kinases JNK and p38 play a role in apoptosis induction by PRRSV infection. We
      examined phosphorylation of JNK and p38, and found that JNK but not p38 was
      activated in response to PRRSV infection. We then examined effects of this kinase
      on apoptosis induction and virus replication by using specific inhibitor. We
      found that JNK inhibition by its inhibitor SP600125 led to the abolishment of
      PRRSV-mediated apoptosis, but did not suppress virus replication. Further studies
      demonstrated that ROS generation was involved in JNK activation, and Bcl-2 family
      anti-apoptotic proteins Mcl-1 and Bcl-xl were downstream targets of JNK to
      mediate apoptosis. We conclude that activation of JNK signaling pathway is
      essential for PRRSV-mediated apoptosis but not for virus replication.

PMID- 22472733
TI  - What clinical records should we retain and for how long?

PMID- 22472735
TI  - The RMS Titanic.

PMID- 22472739
TI  - Response to Dr Gibson's article; mining remains a hazardous occupation.

PMID- 22472740
TI  - How I use it: search engines.

PMID- 22472741
TI  - Assessment of maternal heart-rate variability during labor using wavelet-based
      power spectral analysis.
AB  - OBJECTIVE: Changes in the maternal cardiac autonomic nervous system were assessed
      in the presence and absence of uterine contractions by analyzing maternal heart
      rate variability during labor using wavelet-based power spectral analysis.
      METHODS: We assessed the heart-rate variability in 20 pregnant women during labor
      and in 15 pregnant women with threatened premature labor with the use of wavelet
      based power spectral analysis. RESULTS: There was no significant difference in
      high-frequency components between the uterine contraction and non-contraction
      periods. The intensities of the low-frequency and very-low-frequency components
      during uterine contractions were significantly stronger than the corresponding
      intensities between uterine contractions. CONCLUSION: Maternal sympathetic
      activity was upregulated during uterine contractions, and influenced the very-low
      frequency components. This method of analysis may represent a novel means of
      identifying uterine contractions.

PMID- 22472742
TI  - In vivo evidence of cross-reactivity between cow's milk and soybean proteins in a
      mouse model of food allergy.
AB  - BACKGROUND: Cow's milk allergy (CMA) is an important problem worldwide and the
      development of an in vivo system to study new immunotherapeutic strategies is of
      interest. Intolerance to soybean formula has been described in CMA patients, but
      it is not fully understood. In this work, we used a food allergy model in BALB/c
      mice to study the cross-reactivity between cow's milk protein (CMP) and soy
      proteins (SP). METHODS: Mice were orally sensitized with cholera toxin and CMP,
      and then challenged with CMP or SP to induce allergy. Elicited symptoms, plasma
      histamine, humoral and cellular immune response were analyzed. Th1- and Th2
      associated cytokines and transcription factors were assessed at mucosal sites and
      in splenocytes. Cutaneous tests were also performed. RESULTS: We found that the
      immediate symptoms elicited in CMP-sensitized mice orally challenged with SP were
      consistent with a plasma histamine increase. The serum levels of CMP-specific IgE
      and IgG1 antibodies were increased. These antibodies also recognized soy
      proteins. Splenocytes and mesenteric lymph node cells incubated with CMP or SP
      secreted IL-5 and IL-13. mRNA expression of Th2-associated genes (IL-5, IL-13,
      and GATA-3) was upregulated in mucosal samples. In addition, sensitized animals
      exhibited positive cutaneous tests after the injection of CMP or SP. CONCLUSIONS:
      We demonstrate that CMP-sensitized mice, without previous exposure to soy
      proteins, elicited hypersensitivity signs immediately after the oral
      administration of SP, suggesting that the immunochemical cross-reactivity might
      be clinically relevant. This model may provide an approach to further
      characterize cross-allergenicity phenomena and develop new immunotherapeutic
      treatments for allergic patients.

PMID- 22472743
TI  - Characterization of adult stem/progenitor cell populations from bone marrow in a
      three-dimensional collagen gel culture system.
AB  - Stem cell transplantation therapy using mesenchymal stem cells (MSCs) is
      considered a useful strategy. Although MSCs are commonly isolated by exploiting
      their plastic adherence, several studies have suggested that there are other
      populations of stem and/or osteoprogenitor cells that  are removed from primary
      culture during media replacement. Therefore, we developed a three-dimensional
      (3D) culture system in which adherent and nonadherent stem cells are selected and
      expanded. Here, we described the characterization of 3D culture-derived cell
      populations in vitro and the  capacity of these cells to differentiate into bone
      and/or cartilage tissue when placed inside of demineralized bone matrix (DBM)
      cylinders, implanted subcutaneously into the backs of rat for 2, 4, and 8 weeks.
      Our results demonstrates that 3D culture cells were a heterogeneous population of
      uncommitted cells that express pluripotent-, hematopoietic-, mesenchymal-, and
      endothelial-specific markers in vitro and can undergo osteogenic differentiation
      in vivo.

PMID- 22472744
TI  - Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in
      adult hospitalized patients: a single-center, randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVES: Antibiotic-associated diarrhea (AAD) and Clostridium difficile
      associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics
      were effective in preventing AAD and CDAD in several randomized controlled
      trials. This study was aimed at testing the effect of Saccharomyces boulardii on
      the occurrence of AAD and CDAD in hospitalized patients. METHODS: A single
      center, randomized, double-blind, placebo-controlled, parallel-group trial was
      performed. Patients being prescribed antibiotics or on antibiotic therapy for <48
      h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of
      probiotics, lack of informed consent, inability to ingest capsules, and severe
      pancreatitis. Patients received a capsule containing S. boulardii or an
      indistinguishable placebo twice daily within 48 h of beginning antibiotic
      therapy, continued treatment for 7 days after antibiotic withdrawal, and were
      followed for 12 weeks after ending antibiotic treatment. RESULTS: Of 562
      consecutive eligible patients, 275 patients aged 79.2 +/- 9.8 years (134 on
      placebo) were randomized and 204 aged 78.4 +/- 10.0 years (98 on placebo)
      completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving
      placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S.
      boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases
      of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group
      (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There
      was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). CONCLUSIONS: In
      elderly hospitalized patients, S. boulardii was not effective in preventing the
      development of AAD.

PMID- 22472745
TI  - Effect of dyspepsia on survival: a longitudinal 10-year follow-up study.
AB  - OBJECTIVES: Most chronic and recurrent gastrointestinal (GI) symptoms in the
      community are caused by functional GI disorders, such as functional dyspepsia and
      irritable bowel syndrome (IBS). It is not known, however, whether these
      conditions affect mortality. We present the results of a large community-based
      prospective study that examines this issue. METHODS: This was a 10-year follow
      up, conducted in 2004, of individuals recruited into a community-based screening
      program for Helicobacter pylori. Data on mortality and cause of death at 10 years
      were obtained from the Office for National Statistics. Baseline demographic data,
      lifestyle factors, GI symptoms, and quality of life were recorded at study entry.
      The effect of all these factors on 10-year mortality was examined using
      univariate analysis and multivariate Cox regression analysis. All results were
      expressed as hazard ratios (HRs) with 99% confidence intervals (CIs). RESULTS:
      Symptom data were available for 8,323 (99.0%) of 8,407 individuals originally
      enrolled, comprising over 84,000 years of follow-up: 3,169 (38.1%) subjects had
      dyspepsia, and 264 (3.2%) IBS. There were 137 (1.65%) individuals who had died at
      10 years. After multivariate analysis, there was no significant difference in
      likelihood of death at 10 years in those with dyspepsia (HR: 0.94; 99% CI: 0.58
      1.54) or IBS (HR: 1.35; 99% CI: 0.36-5.10), compared with those not meeting the
      criteria for either condition. CONCLUSIONS: Dyspepsia was not associated with an
      increased mortality in the community. Data for any effect of IBS on survival were
      less clear. Further studies are required to assess the impact of functional GI
      disorders on life expectancy.

PMID- 22472746
TI  - Advanced vibration suppression algorithms in adaptive optics systems.
AB  - Vibration suppression in astronomical adaptive optics (AO) systems has gathered
      great attention in the context of next-generation instrumentation for current
      telescopes and future Extremely Large Telescopes. Laser tomographic AO systems
      require natural guide stars to measure the low-order modes such as tip-tilt (TT)
      and TT-anisoplanatism. To increase the sky coverage, the guide stars are often
      faint, thus requiring lower temporal sampling frequencies to work on a more
      favorable signal-to-noise regime. Such sampling frequencies can be of the order
      of, or even lower than, the range of frequencies where vibrations are likely to
      appear. Ideally, vibrations affecting the low-order modes could be corrected at
      the higher laser loop frame rate using an upsampling procedure. This paper
      compares the most relevant solutions proposed hitherto to a novel multirate
      algorithm using the linear-quadratic-Gaussian (LQG) approach capable of
      upsampling the correction to further reduce the impact of vibrations. Results
      from numerical Monte Carlo simulations span a large range of parameters from pure
      sinusoids to relatively broad peak vibrations, covering the likely-to-be signals
      in a realistic AO system. The improvement is shown at sampling frequencies from
      20 to 800 Hz, including below the vibration itself, in the example of 29.5 Hz on
      a Thirty Meter Telescope-like scenario. The multirate LQG ensures the least
      residual for both faint and bright stars for all the peak widths considered based
      on telemetry from the Keck Observatory.

PMID- 22472747
TI  - Effect of surface plasmons on spectral switching of polychromatic light with Au
      double-slit.
AB  - It is shown that the generation of surface plasmons on a metal-dielectric
      interface, i.e., a Au-double-slit and air interface, appreciably affects the
      intensity of the diffracted light. With a specific example of Au-double-slit and
      electro-optic devices before the slits, the spectral switching in the diffracted
      field with the polychromatic light is shown for the first time, to our knowledge.
      It is found that at the observation point due to the surface plasmon effect the
      intensity of the diffracted light periodically increases and decreases with the
      separation of the double-slit.

PMID- 22472748
TI  - Designation of lenses with a single freeform surface for multiple point sources.
AB  - Optical lenses with a freeform surface can be designed for diverse illumination
      profiles with uniformity. However, most of the previous studies formulate the
      problem for a single point source, and the lens topology has freeform top and
      spherical bottom surfaces. In this study, the formulation is extended for
      multiple point sources, and a flat surface is included in the lens bottom
      topology for ease of prototyping and manufacturing. The extended formulation for
      multiple point sources requires only a freeform surface to design. The
      formulation of overdetermined coupling equations is solved by applying the
      weighted least-square method. The weightings are correlated with the emitting
      intensities of sources in terms of an inverse gamma function. The weighting
      scheme gives a parameter space for designation of illumination profile fit and
      uniformity. The adequacy of the extended formulation is demonstrated by
      simulation. Examples of circular and rectangular illumination for single and
      multiple point sources are studied. The simulation results show that unbalanced
      luminance distribution can be induced by an offset source and collimated by a
      lens, which is designated by taking the offset into account. For multiple point
      sources, illumination profile fit and uniformity are designated in trade off
      based on the parameter design.

PMID- 22472749
TI  - Study of incident angle dependence for dual-band double negative-index material
      using elliptical nanohole arrays.
AB  - This work demonstrates the angular dependence of dual-band negative-index
      materials implemented by elliptical nanohole arrays (ENAs) consisting of an Al2O3
      dielectric layer between two Au films. This article, it is believed for the first
      time, analyzes the scattering coefficients and displacement current of the ENA at
      different angles of plane-wave incidence to show that the ENA is double negative
      (showing both a negative effective permeability MU(eff) and a negative effective
      permittivity epsilon(eff) at multiple wavelengths (1095 and 1680 nm) for p
      polarization over a broad range of incident angles.

PMID- 22472750
TI  - High-efficiency x-ray gratings with asymmetric-cut multilayers.
AB  - We present the fabrication and analysis of efficient and highly dispersive
      gratings for the x-ray and extreme ultraviolet (EUV) regime. We show that an
      asymmetric-cut multilayer structure can act as a near-perfect blazed grating. The
      precision and high line density are achieved by layer deposition of materials,
      which can be controlled to the angstrom level. We demonstrate this in the EUV
      regime with two structures made by cutting and polishing magnetron-sputtered
      multilayer mirrors of over 2000 bilayers thick, each with a period of 6.88 nm.
      These were cut at angles of 2.9 degrees  and 7.8 degrees  to the surface. Within
      the 3% bandwidth rocking curve of the multilayer, the angular dispersion of the
      diffracted wave was in agreement with the grating equation for elements with 7250
      and 19,700 line pairs/mm, respectively. The dependence of the measured efficiency
      was in excellent agreement with a formulation of dynamical diffraction theory for
      multilayered structures. At a wavelength of 13.2 nm, the efficiency of the first
      order diffraction was over 95% of the reflectivity of the uncut multilayer. We
      predict that such structures should also be effective at shorter x-ray
      wavelengths. Both the Laue (transmitting) and Bragg (reflecting) geometries are
      incorporated in our formalism, which is applied to the analysis of multilayer
      Laue lenses and focusing and dispersing Bragg optics.

PMID- 22472751
TI  - Modeling the diffuse reflectance due to a narrow beam incident on a turbid
      medium.
AB  - We present a model for the diffuse reflectance when a continuous beam is incident
      normally on a half space composed of a uniform scattering and absorbing medium.
      This model is the result of an asymptotic analysis of the radiative transport
      equation for strong scattering, weak absorption, and a narrow beam width. Through
      comparison with the diffuse reflectance computed using the numerical solution of
      the radiative transport equation, we show that this diffuse reflectance model
      gives results that are accurate for small source--detector separation distances.

PMID- 22472752
TI  - Toward a cylindrical cloak via inverse homogenization.
AB  - An effective cylindrical cloak may be conceptualized as an assembly of adjacent
      local neighborhoods, each of which is made from a homogenized composite material
      (HCM). The HCM is required to be a certain uniaxial dielectric-magnetic material,
      characterized by positive-definite constitutive dyadics. It can arise from the
      homogenization of component materials that are remarkably simple in terms of
      their structure and constitutive relations. For example, the components can be
      two isotropic dielectric-magnetic materials, randomly distributed as oriented
      spheroidal particles. By carefully controlling the spheroidal shape of the
      component particles, a high degree of HCM anisotropy may be achieved which is
      necessary for the cloaking effect to be realized. The inverse Bruggeman formalism
      can provide estimates of the shape and constitutive parameters for the component
      materials, as well as their volume fractions.

PMID- 22472753
TI  - Reconstruction in interferometric synthetic aperture microscopy: comparison with
      optical coherence tomography and digital holographic microscopy.
AB  - It is shown that the spatial frequencies recorded in interferometric synthetic
      aperture microscopy do not correspond to exact backscattering [as they do in
      unistatic synthetic aperture radar (SAR)] and that the reconstruction process
      based on SAR is therefore based on an approximation. The spatial frequency
      response is developed based on the three-dimensional coherent transfer function
      approach and compared with that in optical coherence tomography and digital
      holographic microscopy.

PMID- 22472754
TI  - Study on the propagation parameters of Bessel-Gaussian beams carrying optical
      vortices through atmospheric turbulence.
AB  - Based on the integral representation of Bessel function and the extended Huygens
      Fresnel principle, an integral expression of the Wigner distribution function
      (WDF) for partially coherent Bessel-Gaussian beams (PBGBs) propagating through
      turbulent atmosphere has been obtained. Also, the analytical formulas of the M2
      factor for PBGB propagation in such a medium have been derived, which can be
      applied to cases of different spatial power spectra of the refractive index
      fluctuations. The performed numerical results reveal that the M2-factor of a PBGB
      in turbulent atmosphere depends on the beam parameters of the initial input beam,
      the structure constants of the turbulent atmosphere, and the propagation
      distance. These results may be useful in long-distance optical communications in
      free space or in turbulent atmosphere.

PMID- 22472755
TI  - Comparison of two scanning instruments to measure peripheral refraction in the
      human eye.
AB  - To better understand how peripheral refraction affects development of myopia in
      humans, specialized instruments are fundamental for precise and rapid
      measurements of refraction over the visual field. We compare here two prototype
      instruments that measure in a few seconds the peripheral refraction in the eye
      with high angular resolution over a range of about +/-45 deg. One instrument is
      based on the continuous recording of Hartmann-Shack (HS) images (HS scanner) and
      the other is based on the photorefraction (PR) principle (PR scanner). On
      average, good correlations were found between the refraction results provided by
      the two devices, although it varied across subjects. A detailed statistical
      analysis of the differences between both instruments was performed based on
      measurements in 35 young subjects. Both instruments have advantages and
      disadvantages. The HS scanner also provides the high-order aberration data, while
      the PR scanner is more compact and has a lower cost. Both instruments are current
      prototypes, and further optimization is possible to make them even more suitable
      tools for future visual optics and myopia research and also for different
      ophthalmic applications.

PMID- 22472756
TI  - Highly efficient broadband conversion of light polarization by composite
      retarders.
AB  - Driving on an analogy with the technique of composite pulses in quantum physics,
      we propose highly efficient broadband polarization converters composed of
      sequences of ordinary retarders rotated at specific angles with respect to their
      fast-polarization axes.

PMID- 22472757
TI  - Monte Carlo simulation of the field back-scattered from rough surfaces.
AB  - A novel approach for the simulation of the field back-scattered from a rough
      surface is presented. It takes into account polarization and multiple scattering
      events on the surface, as well as diffraction effects. The validity and
      usefulness of this simulation is demonstrated in the case of surface topology
      measurement.

PMID- 22472758
TI  - Polarization changes at Lyot depolarizer output for different types of input
      beams.
AB  - Lyot depolarizers are optical devices made of birefringent materials used for
      producing unpolarized beams from totally polarized incident light. The
      depolarization is produced for polychromatic input beams due to the different
      phase introduced by the Lyot depolarizer for each wavelength. The effect of this
      device on other types of incident fields is investigated. In particular two cases
      are analyzed: (i) monochromatic and nonuniformly polarized incident beams and
      (ii) incident light synthesized by superposition of two monochromatic
      orthogonally polarized beams with different wavelengths. In the last case, it is
      theoretically and experimentally shown that the Lyot depolarizer increases the
      degree of polarization instead of depolarizes.

PMID- 22472759
TI  - Two-dimensional relativistic longitudinal Green's function in the presence of a
      moving planar dielectric-magnetic discontinuity.
AB  - The current contribution is concerned with obtaining the relativistic two
      dimensional (three-dimensional in relativity jargon) Green's function of a time
      harmonic line current that is embedded in a moving dielectric-magnetic medium
      with a planar discontinuity. By applying a plane-wave (PW) spectral
      representation for the relativistic electromagnetic Green's function of a
      dielectric-magnetic medium that is moving in a uniform velocity, the exact
      reflected and transmitted (refracted) fields are obtained in the form of a
      spectral integral over PWs in the so-called laboratory and comoving frames. We
      investigate these spectral representations, as well as their asymptotic
      evaluations, and discuss the associated relativistic wave phenomena of direct
      reflected/transmitted rays and relativistic head waves (lateral waves).

PMID- 22472760
TI  - Optical aperture synthesis imaging with fractional Fourier-domain filtering.
AB  - The fractional Fourier transform, which is a generalization of the classical
      Fourier transform, is introduced into an optical aperture synthesis (OAS) system
      by which imaging of an astronomical object can be achieved. We introduce
      fractional Fourier optical imaging and fractional Fourier-domain filtering
      (FFDF), and then present the schematic diagram of an OAS imaging system with
      FFDF. The modulation transfer function of an OAS system with FFDF is compared
      with that of an OAS system in the same condition. The result indicates that the
      OAS system with FFDF has larger practical cutoff frequency when the fill factor
      is smaller. Furthermore, the quality of imaging and restoration also demonstrates
      this conclusion.

PMID- 22472761
TI  - Photoluminescence from a homogeneous volume source within an optical multilayer:
      analytical formulas.
AB  - A theoretical model for light emission from a homogeneous volume source, such as
      an optically active layer, within a multilayer is demonstrated. The role of an
      external linearly polarized optical pump is taken into account. The resulting
      formulas for the radiated powers are fully analytical. They are applied to
      investigate the effect of a plane-wave pump in a basic lambda/2 cavity and to
      calculate the photoluminescence polar diagrams of color centers from three
      resonating thin-film lithium-fluoride-based microstructures.

PMID- 22472762
TI  - Worldwide prevalence of red-green color deficiency.
AB  - Literature that describes the prevalence of inherited red-green color deficiency
      in different populations is reviewed. Large random population surveys show that
      the prevalence of deficiency in European Caucasians is about 8% in men and about
      0.4% in women and between 4% and 6.5% in men of Chinese and Japanese ethnicity.
      However, the male: female prevalence ratio is markedly different in Europeans and
      Asians. Recent surveys suggest that the prevalence is rising in men of African
      ethnicity and in geographic areas that have been settled by incoming migrants. It
      is proposed that founder events and genetic drift, rather than natural selection,
      are the cause of these differences.

PMID- 22472764
TI  - Experimental results for improving the matrix condition using a hybrid optical
      system.
AB  - We present preliminary experimental results for implementing the "blurred
      trajectories" method on three parallel optics (PO) systems. The "main" system and
      "auxiliary" optics were simple laboratory graded lenses attached to an iris
      diaphragm. When applying the blurred trajectories method we first show an
      improvement in the matrix condition, as the matrix condition number decreased in
      a range of factors of 3 to 418 relative to the main system. Following that, image
      restoration by weak regularization was performed so that the system matrix
      condition dominated the restoration process. It was shown that the restoration
      results of the PO are better than those of the main system and the auxiliary
      optics separately. In addition, the quality of the restoration follows the
      system's matrix condition. The improvement in the matrix condition achieved by
      the PO system improved the immunity to detection noise. Finally, a comparison to
      Wiener filtering restoration shows that it is also generally inferior to the
      proposed method.

PMID- 22472763
TI  - Information loss and reconstruction in diffuse fluorescence tomography.
AB  - This paper is a theoretical exploration of spatial resolution in diffuse
      fluorescence tomography. It is demonstrated that, given a fixed imaging geometry,
      one cannot-relative to standard techniques such as Tikhonov regularization and
      truncated singular value decomposition-improve the spatial resolution of the
      optical reconstructions via increasing the node density of the mesh considered
      for modeling light transport. Using techniques from linear algebra, it is shown
      that, as one increases the number of nodes beyond the number of measurements,
      information is lost by the forward model. It is demonstrated that this
      information cannot be recovered using various common reconstruction techniques.
      Evidence is provided showing that this phenomenon is related to the smoothing
      properties of the elliptic forward model that is used in the diffusion
      approximation to light transport in tissue. This argues for reconstruction
      techniques that are sensitive to boundaries, such as L1-reconstruction and the
      use of priors, as well as the natural approach of building a measurement geometry
      that reflects the desired image resolution.

PMID- 22472765
TI  - Super-resolved spatial light interference microscopy.
AB  - We report a scheme to achieve resolution beyond the diffraction limit in spatial
      light interference microscopy (SLIM). By adding a grating to the optical path,
      the structured illumination technique can be used to improve the resolution by a
      factor of 2. We show that a direct application of the structured illumination
      technique, however, has proved to be unsuccessful. Through two crucial
      modifications, namely, one to the pupil plane of the objective and the other to
      the demodulation procedure, faithful phase information of the object is recovered
      and the resolution is improved by a factor of 2.

PMID- 22472766
TI  - Scattering from cylinders using the two-dimensional vector plane wave spectrum:
      addendum.
AB  - The solution for the vector plane wave spectrum scattering from multiple
      cylinders by Pawliuk and Yedlin [J. Opt. Soc. A28, 1177 (2011)] only provided the
      single scattering coefficients for the TM polarization case. The TE solution is
      similar except for the form of the single scattering coefficients. Here we
      describe the single scattering coefficients for both polarizations and three
      types of cylinders: dielectrics, perfect electric conductors, and perfect
      magnetic conductors.

PMID- 22472767
TI  - New error bounds for M-testing and estimation of source location with
      subdiffractive error.
AB  - I present new lower and upper bounds on the minimum probability of error (MPE) in
      Bayesian multihypothesis testing that follow from an exact integral of a version
      of the statistical entropy of the posterior distribution, or equivocation. I also
      show that these bounds are exponentially tight and thus achievable in the
      asymptotic limit of many conditionally independent and identically distributed
      measurements. I then relate the minimum mean-squared error (MMSE) and the MPE by
      means of certain elementary error probability integrals. In the second half of
      the paper, I compare the MPE and MMSE for the problem of locating a single point
      source with subdiffractive uncertainty. The source-strength threshold needed to
      achieve a desired degree of source localization seems to be far more modest than
      the well established threshold for the different optical super-resolution problem
      of disambiguating two point sources with subdiffractive separation.

PMID- 22472768
TI  - Application of the three-dimensional aperiodic Fourier modal method using arc
      elements in curvilinear coordinates.
AB  - This paper deals with a full vectorial generalization of the aperiodic Fourier
      modal method (AFMM) in cylindrical coordinates. The goal is to predict some key
      characteristics such as the bending losses of waveguides having an arbitrary
      distribution of the transverse refractive index. After a description of the
      method, we compare the results of the cylindrical coordinates AFMM with
      simulations by the finite-difference time-domain (FDTD) method performed on an S
      bend structure made by a 500 nm * 200 nm silicon core (n=3.48) in silica (n=1.44)
      at a wavelength lambda=1550 nm, the bending radius varying from 0.5 up to 2 MUm.
      The FDTD and AFMM results show differences comparable to the variations obtained
      by changing the parameters of the FDTD simulations.

PMID- 22472769
TI  - Color space transformations for digital photography exploiting information about
      the illuminant estimation process.
AB  - The color reproduction accuracy is a key factor to the overall perceived image
      quality in digital photography. In this framework, both the illuminant estimation
      process and the color correction matrix concur in the formation of the overall
      perceived image quality. To the best of our knowledge, the two processes have
      always been studied separately, thus ignoring the interactions between them. We
      investigate here these interactions, showing how the color correction transform
      amplifies the illuminant estimation errors. We demonstrate that incorporating
      knowledge about the illuminant estimation behavior in the optimization of the
      color correction matrix makes it possible to alleviate the error amplification.
      Different strategies to improve color accuracy under both perfect and imperfect
      white point estimations are investigated, and the experimental results obtained
      with a digital camera simulator are reported.

PMID- 22472770
TI  - Independent multifunctional detection by wettability controlled inverse opal
      hydrogels.
AB  - Utilizing the wettability of inverse opal hydrogels, we report a new strategy to
      construct photonic hydrogels with multiple types of reliable signals, such as non
      wetting (transparent), image contrast (weak color) with shifts of diffraction
      maximum (bright color), developing optical sensors for multifunctional detection.

PMID- 22472771
TI  - Response to Anandarajan et al.: Manic exacerbation induced by nicotine patch.

PMID- 22472772
TI  - The impact of alcohol and illicit drugs on people with psychosis: the second
      Australian National Survey of Psychosis.
AB  - OBJECTIVE: To provide the most up-to-date prevalence estimates of alcohol and
      illicit drug use among individuals with psychosis in Australia, and explore
      correlates associated with a lifetime diagnosis of both alcohol abuse/dependence
      and cannabis abuse/dependence. METHOD: This paper uses data from the Survey of
      High Impact Psychosis (SHIP), conducted as a follow-up to the first Australian
      National Low Prevalence (Psychotic) Disorders Study (1997-1998). The SHIP was a
      national study, carried out across five states, in which a sample of 1825
      individuals was recruited through a two-phase sampling framework. RESULTS:
      Alcohol and illicit drug use was highly prevalent for the entire sample. There
      were few significant differences in the prevalence or frequency of use across the
      diagnostic categories examined. Substantial increases in substance
      abuse/dependence were noted since the 1997-1998 survey (51% diagnosed with
      alcohol abuse/dependence, 51% with cannabis abuse/dependence and 32% with other
      illicit drug abuse/dependence, compared to 28%, 23% and 12% respectively, in the
      1997-1998 survey by Kavanagh et al., 2004). Factors significantly associated with
      both lifetime alcohol and cannabis dependence included male gender, younger age,
      single marital status, lower educational attainment, shorter duration of illness,
      lifetime presence of hallucinations, higher negative syndrome score and lower
      body mass index (BMI). A number of other factors were found to be differentially
      associated with either lifetime alcohol or cannabis dependence. CONCLUSIONS: The
      use of alcohol and illicit substances is common among people with a psychotic
      illness, with a concerning upward trend in rates of substance abuse/dependence
      since the 1997-1998 survey. Clinicians should be aware of the potential impact of
      concurrent substance use and provide integrated treatment for individuals
      presenting with psychotic illnesses. More research and investment in new
      intervention programs is required.

PMID- 22472773
TI  - Lung B cells promote early pathogen dissemination and hasten death from
      inhalation anthrax.
AB  - Sampling of mucosal antigens regulates immune responses but may also promote
      dissemination of mucosal pathogens. Lung dendritic cells (LDCs) capture antigens
      and traffic them to lung-draining lymph nodes (LDLNs) dependent on the chemokine
      receptor CCR7 (chemokine (C-C motif) receptor 7). LDCs also capture lung
      pathogens such as Bacillus anthracis (BA). However, we show here that the initial
      traffic of BA spores from lungs to LDLNs is largely independent of LDCs and CCR7,
      occurring instead in association with B cells. BA spores rapidly bound B cells in
      lungs and cultured mouse and human B cells. Binding was independent of the B-cell
      receptor (BCR). B cells instilled in the lungs trafficked to LDLNs and BA spore
      traffic to LDLNs was impaired by B-cell deficiency. Depletion of B cells also
      delayed death of mice receiving a lethal BA infection. These results suggest that
      mucosal B cells traffic BA, and possibly other antigens, from lungs to LDLNs.

PMID- 22472774
TI  - Neuroimmune semaphorin 4A downregulates the severity of allergic response.
AB  - To define the role of semaphorin 4A (Sema4A) in allergic response, we employed
      Sema4A-/- and wild-type (WT) mice in the experimental model of ovalbumin (OVA)
      induced allergic airway inflammation. We observed a selective increase in
      eosinophilic airway infiltration accompanied by bronchial epithelial cell
      hyperplasia in allergen-treated Sema4A-/- mice relative to WT mice. This enhanced
      inflammatory response was associated with a selective increase in bronchoalveolar
      lavage (BAL) interleukin 13 (IL-13) content, augmented airway hyperreactivity,
      and lower regulatory T cell (Treg) numbers. In vivo allergen-primed Sema4A-/-
      CD4+ T cells were more effective in transferring T helper type 2 (Th2) response
      to naive mice as compared with WT CD4+ T cells. T-cell proliferation and IL-13
      productions in OVA323-339-restimulated Sema4A-/- cell cultures were upregulated.
      Generated bone marrow chimeras showed an equal importance of both lung-resident
      cell and inflammatory cell Sema4A expression in optimal disease regulation. These
      data provide a new insight into Sema4A biology and define Sema4A as an important
      regulator of Th2-driven lung pathophysiology.

PMID- 22472775
TI  - CD8alpha+beta- and CD8alpha+beta+ plasmacytoid dendritic cells induce Foxp3+
      regulatory T cells and prevent the induction of airway hyper-reactivity.
AB  - Dendritic cells (DCs) control the balance between protection against pathogens
      and tolerance to innocuous or self-antigens. Here, we demonstrate for the first
      time that mouse plasmacytoid DCs (pDCs) can be segregated into three distinct
      populations, exhibiting phenotypic and functional differences, according to their
      surface expression of CD8alpha or CD8beta as CD8alpha-beta-, CD8alpha+beta-, or
      CD8alpha+beta+. In a mouse model of lung inflammation, adoptive transfer of
      CD8alpha+beta- or CD8alpha+beta+ pDCs prevents the development of airway hyper
      reactivity. The tolerogenic features of these subsets are associated with
      increased production of retinoic acid, which leads to the enhanced induction of
      Foxp3+ regulatory T cells compared with CD8alpha-beta- pDCs. Our data thus
      identify subsets of pDCs with potent tolerogenic functions that may contribute to
      the maintenance of tolerance in mucosal sites such as the lungs.

PMID- 22472776
TI  - Identification of novel coding mutation in C1qA gene in an African-American
      pedigree with lupus and C1q deficiency.
AB  - OBJECTIVES: Homozygous C1q deficiency is an extremely rare condition and strongly
      associated with systemic lupus erythematosus. To assess and characterize C1q
      deficiency in an African-American lupus pedigree, C1q genomic region was
      evaluated in the lupus cases and family members. METHODS: Genomic DNA from
      patient was obtained and C1q A, B and C gene cluster was sequenced using next
      generation sequencing method. The identified mutation was further confirmed by
      direct Sanger sequencing method in the patient and all blood relatives. C1q
      levels in serum were measured using sandwich ELISA method. RESULTS: In an African
      American patient with lupus and C1q deficiency, we identified and confirmed a
      novel homozygote start codon mutation in C1qA gene that changes amino acid
      methionine to arginine at position 1. The Met1Arg mutation prevents protein
      translation (Met1Arg). Mutation analyses of the patient's family members also
      revealed the Met1Arg homozygote mutation in her deceased brother who also had
      lupus with absence of total complement activity consistent with a recessive
      pattern of inheritance. CONCLUSION: The identification of new mutation in C1qA
      gene that disrupts the start codon (ATG to AGG (Met1Arg)) has not been reported
      previously and it expands the knowledge and importance of the C1q gene in the
      pathogenesis of lupus especially in the high-risk African-American population.

PMID- 22472777
TI  - Rheumatologic rehabilitation: the great expectation for rheumatic patients.

PMID- 22472778
TI  - MicroRNAs in autoimmune rheumatic diseases.
AB  - The etiology of autoimmune diseases remains largely unknown. In recent years,
      besides genetic factors, several studies proposed that the epigenome may hold the
      key to a better understanding of autoimmunity initiation and perpetuation. More
      specifically epigenetic regulatory mechanisms comprise DNA methylation, a variety
      of histone modifications, and microRNA (miRNA) activity, all of which act upon
      gene and protein expression levels. In particular it is well known that
      epigenetic mechanisms are important for controlling the pattern of gene
      expression during development, the cell cycle, and the response to biological or
      environmental changes. In the present review a description of the most frequent
      epigenetic deregulations, in particular the role of miRNAs, in rheumatic
      autoimmune disorders will be investigated.

PMID- 22472779
TI  - Adherence to therapeutic and diagnostic recommendations in patients with femur
      fracture and at risk of re-fracture or death: results of an analysis of
      administrative databases.
AB  - The aim of the present study was to evaluate the application into clinical
      practice of therapeutic and diagnostic recommendations for the prevention of bone
      re-fracture in postmenopausal women after an hospitalization for hip fracture in
      clinical practice and to assess the relationship between the application of
      diagnostic recommendations and re-fracture or death risk. A retrospective cohort
      analysis was conducted.  All female patients, at least 65 years old, and with an
      hospitalization with main or secondary diagnosis of hip fracture during the
      period 1 January 2006 - 31 December 2008, were included. Besides demographic
      characteristics and comorbidities, drug treatment prescriptions related to bone
      fracture or supplementary with calcium or vitamin D and prescriptions of
      recommended laboratory and instrumental diagnostic tests (e.g. spine
      radiography), were analysed. A total of 5,636 patients were included in the
      study. The prescription of a drug treatment aimed to reduce the risk of re
      fracture was found in 16.3% of patients, among them 76.3% (699 patients) used
      bisphosphonates only, 17.1% (157 patients) strontium ranelate only and 4.9% (45
      patients) used more than one treatment during the observation period. Among the
      patients who did not receive drug treatment, 17.5% made use of only supplemental
      calcium and vitamin D. The remaining part of patients (69.1%) received no
      treatment. The prescription of at least one laboratory test of first and second
      level was performed, respectively, on 53.7% and 43.1% of included patients,
      whereas the prescription of at least one instrumental test of first and second
      level was performed, respectively, on 5.9% and 0.8%. Although it is established
      that the prescription of the recommended tests and appropriate drug treatment are
      significantly associated with reduced risk of re-fracture and death, today the
      application of these recommendations is reduced.

PMID- 22472780
TI  - Preliminary identification of key clinical domains for outcome evaluation in
      fibromyalgia using the Delphi method: the Italian experience.
AB  - OBJECTIVE: Fibromyalgia (FM) is a complex syndrome that, in Italy, affects at
      least 2% of the adult population. It is characterized by chronic widespread
      musculoskeletal pain often accompanied by multiple other symptoms. The aim of
      this study was to identify a set of clinical domains for FM considered relevant
      by both clinicians and patients using a consensus process. METHODS: Consensus was
      achieved using the Delphi method based on questionnaires and systematic,
      controlled opinion feedback. The Delphi exercise involved a panel of 252
      rheumatologists and 86 patients with FM as defined by the American College of
      Rheumatology criteria. All of the patients and clinicians were asked to rank the
      relative different domains of FM in order of priority. The content validity index
      (CVI) was used to establish the percentage agreement. The importance of each item
      was ranked on a 0-3 Likert scale. The frequency, mean relevance scores, and
      frequency importance product were also calculated. RESULTS: The Delphi exercise
      showed that the domains ranked highest by patients were similar to those of the
      clinicians, with the exception of tender point intensity (considered relevant by
      the clinicians but not by the patients) and environmental sensitivity (considered
      important by the patients but not by the clinicians). A final 8-item model was
      developed which was considered to demonstrate adequate validity. CONCLUSIONS: The
      Delphi exercises identified and ranked relevant key clinical domains that need to
      be assessed in FM research. On the basis of these results, a new patient-reported
      composite outcome index can be developed and used in clinical trials.

PMID- 22472781
TI  - In vitro effect of anti-beta2 glycoprotein I antibodies on P-selectin expression,
      a marker of platelet activation.
AB  - OBJECTIVE: Antiphospholipid antibodies (aPL) associated with thrombembolic events
      and/or pregnancy morbidity characterize the so-called antiphospholipid syndrome
      (APS). Beta2glycoprotein I (beta2GPI) represents the major target antigen for
      aPL, but the pathogenic role of anti-beta2GPI antibodies (abeta2GPI) is still
      unclear. Some authors assume they play a role in activating platelets. The
      effects of abeta2GPI antibodies on platelet P-selectin expression were evaluated
      in this study. METHODS: Abeta2GPI antibodies in the plasma of a pregnant APS
      patient were isolated by affinity chromatography during two different stages
      (catastrophic and quiescent) of the disease. Gel filtered platelets (100,000/MUl)
      from healthy volunteers were incubated with beta2-GPI (20 MUg/ml) and with
      different concentrations (5, 25 e 50 MUg/ml) of abeta2GPI antibodies. P-selectin
      surface expression on platelets was assessed by flow cytometry using a specific
      fluorescent antibody directed against P-selectin. RESULTS: Abeta2GPI antibodies
      induced platelet activation only in the presence of thrombin receptor activator
      for peptide 6 (TRAP-6), a platelet agonist, at a subthreshold concentration.
      Abeta2GPI antibody enhancement on platelet surface P-selectin expression was
      stronger in the catastrophic than in the quiescent phase of the disease (47%
      versus 15%). CONCLUSIONS: TRAP-6 dependent platelet activation by abeta2GPI
      antibodies is consistent with the "two hit" pathogenetic hypothesis for
      thrombosis. Abeta2GPI antibodies induce higher platelet P-selectin expression
      during the active rather than in the acute phases.

PMID- 22472782
TI  - Clinical manifestation of selective IgA deficiency evidence after anti-TNF-alpha
      treatment in a psoriatic arthritis patient: case report.
AB  - It is known that the use of anti-TNF-alpha drugs is related to an increased
      incidence of infective diseases. This therapy can not be administered to patients
      having active infections and it has to be considered with caution in case of
      acquired or congenital immunodeficiency diseases. We report the case of a 28
      years-old man affected by psoriatic arthritis; he developed some infections
      during treatment with TNF-alpha blockers. The infections were caused by a
      selective IgA deficiency, that was not evident before the anti-TNF-alpha blockers
      administration and disappeared after withdrawing the biological therapy. This
      case-report draws our attention to the possibility of cases of subclinical
      immunodeficiency, unknown by the patients, but important in the prognosis and in
      the therapeutic approach to these diseases. Therefore, it is important to
      evaluate carefully the immunologic status of patients during the pre-therapeutic
      screening for TNF-alpha blocking therapy.

PMID- 22472783
TI  - A short story of anti-rheumatic therapy. VIII. The immunodepressants.
AB  - The use of immunosuppressive drugs in rheumatology is fairly recent, starting
      just after the Second World War with the introduction of the first alkylating
      agents in oncohematology. When it became clear that some rheumatic diseases,
      particularly rheumatoid arthritis and systemic lupus erythematosus, showed an
      immune-mediated pathogenesis, including proliferation of immunocompetent cells,
      an application was soon found for immunosuppressive drugs in their treatment.
      This review outlines the historical milestones that led to the current use of
      drugs belonging to the major groups of immunosuppressants, i.e. alkylating agents
      (cyclophosphamide), folic acid (methotrexate) and purine (azathioprine)
      antagonists. We will also talk about the history of cyclosporin A, the first
      "selective" immunosuppressive agent, and that of some immunoactive drugs used
      more recently in rheumatology, such as mycophenolate mofetil, dapson and
      thalidomide, is briefly described.

PMID- 22472784
TI  - Association study of the beta-arrestin 2 gene (ARRB2) with opioid and cocaine
      dependence in a European-American population.
AB  - The rewarding properties of drugs of abuse are mediated by the mu-opioid receptor
      (MOR). Genetic variations in MOR and MOR interacting proteins (MORIPs) involved
      in MOR signaling may increase the risk for drug dependence. The MORIP beta
      arrestin plays an important role in the regulation of MOR trafficking, thereby
      highlighting it as a candidate gene for addiction phenotypes. In this case
      control association study, DNA samples from cocaine-dependent (n=336) and opioid
      dependent (n=335) patients and controls (n=656) were genotyped for seven single
      nucleotide polymorphisms (rs11868227, rs3786047, rs4522461, rs1045280, rs2271167,
      rs2036657, and rs4790694) across ARRB2, the gene encoding the beta-arrestin 2
      protein. No significant differences were observed in genotype or allele frequency
      between drug-dependent and control individuals for any of the single nucleotide
      polymorphisms analyzed. Haplotype analysis was similarly negative. Further
      studies are needed to determine whether variations in ARRB2 (or other MORIPs) are
      relevant to cocaine or opioid dependence in different ethnic populations or
      whether they confer a risk that is specific to dependence on other drugs of
      abuse.

PMID- 22472785
TI  - Intracerebral hemorrhage following intravenous thrombolysis in Thai patients with
      acute ischemic stroke.
AB  - In Asia, there is limited information regarding symptomatic intracerebral
      hemorrhage (ICH) in patients treated with intravenous (iv) recombinant tissue
      plasminogen activator (rtPA). The aim of this study was to identify independent
      factors associated with symptomatic ICH following iv rtPA. The study included 192
      patients with acute ischemic stroke who were treated with iv rtPA. Baseline
      characteristics were compared between patients with or without ICH. Symptomatic
      ICH occurred in 5.7% of patients and asymptomatic ICH in 13.0% of patients. An
      international normalized ratio (INR) >=1.0 (odds ratio [OR]=4.89, p=0.036),
      atrial fibrillation (OR=7.21, p=0.009) and blood glucose concentration >8.325
      mmol/L (OR=9.00, p=0.004), were independent risk factors for symptomatic ICH.
      Atrial fibrillation (OR=3.56, p=0.012) and severe stroke (National Institutes of
      Health Stroke Scale >=15; OR=8.94, p<0.001) were independent risk factors for
      asymptomatic ICH. The prevalence of symptomatic ICH following iv rtPA in Thai
      patients was comparable to previous studies.

PMID- 22472786
TI  - Sorption of perfluorooctane sulfonate (PFOS) on marine sediments.
AB  - Sorption of anionic perfluorooctane sulfonate (PFOS) on marine sediment was
      investigated in detail. It was found that solution ionic composition and sediment
      specific parameters played important roles in affecting the sorption of PFOS. The
      results indicated that sorption of PFOS in seawater to marine sediments was
      strong (~ 10 times higher than that in freshwater) and nonlinear (Freundlich n(F)
      values of 0.77-0.96). The sorption affinity was well correlated with sediment
      organic carbon content, indicating the importance of hydrophobic interactions. At
      a PFOS aqueous concentration of 10 MUg/L, PFOS distribution coefficients
      increased with the increasing salinity in solution, with an average rate of 0.48
      +/- 0.03 log units per a log unit of salinity. Further studies demonstrated that
      among common ions contributing to the salinity in seawater, dissolved calcium and
      magnesium are dominantly responsible for the sorption-enhancing effect of
      salinity for PFOS. This work will aid in better understanding of PFOS sorption
      mechanisms, and be useful for fate modeling of this class of contaminants in the
      marine environment.

PMID- 22472787
TI  - Comparison of recreational health risks associated with surfing and swimming in
      dry weather and post-storm conditions at Southern California beaches using
      quantitative microbial risk assessment (QMRA).
AB  - Southern California is an increasingly urbanized hotspot for surfing, thus it is
      of great interest to assess the human illness risks associated with this popular
      ocean recreational water sport from exposure to fecal bacteria contaminated
      coastal waters. Quantitative microbial risk assessments were applied to eight
      popular Southern California beaches using readily available enterococcus and
      fecal coliform data and dose-response models to compare health risks associated
      with surfing during dry weather and storm conditions. The results showed that the
      level of gastrointestinal illness risks from surfing post-storm events was
      elevated, with the probability of exceeding the US EPA health risk guideline up
      to 28% of the time. The surfing risk was also elevated in comparison with
      swimming at the same beach due to ingestion of greater volume of water. The study
      suggests that refinement of dose-response model, improving monitoring practice
      and better surfer behavior surveillance will improve the risk estimation.

PMID- 22472788
TI  - Distribution and controlling factors of phytoplankton assemblages in a semi
      enclosed bay during spring and summer.
AB  - The phytoplankton assemblages' patterns and their correlation to environmental
      factors were studied in Bohai Bay during spring and summer. Two zones, the
      northern (NWA) and southern (SWA) water area, were identified by cluster analysis
      based on their physical and chemical properties. Principal component analysis
      (PCA) showed that more phytoplankton species was found in the SWA with low
      nutrient concentration, while high phytoplankton abundance occurred in the NWA
      with high nutrient concentration. The seasonal variability in phytoplankton can
      be explained by water temperature, nutrient, and hydrodynamic conditions
      (includes mixing during spring and stratification during summer). Results of
      redundancy analysis (RDA) showed that silicate (SiO(4)) and soluble reactive
      phosphorus (SRP) were the most important environmental factors influencing the
      phytoplankton distribution during spring and summer, respectively. Hydrodynamics
      condition plays a key role in controlling variation of the environmental factors,
      which determined phytoplankton distribution in Bohai Bay.

PMID- 22472789
TI  - Ontogeny of the interferon system in chickens.
AB  - Newborn vertebrates may be susceptible to infection because the immature status
      of their immune system results in an inability to make an effective immune
      response. Consequently, newly hatched chicks appear to be more susceptible to
      infections than mature chickens. In particular, poultry susceptibility to virus
      infection may be related to poor expression of innate immune elements involved in
      antiviral responses. Therefore, in this study we assessed the relative
      development of the interferon (IFN) system: a protective system against virus
      infection. We investigated the age-related expression of the elements involved in
      the IFN response including IFN gene expression, their associated receptors and
      the pattern recognition receptors (PRR) involved in the regulation of IFNs. We
      observed that the IFN system is somewhat inadequately expressed in embryos and
      develops over time, just prior to and after hatching, and therefore chicks may be
      more susceptible to virus than mature birds because of an immature IFN network.

PMID- 22472790
TI  - Dr. Jekyll or Mr. Hyde? (How) the Internet influences vaccination decisions:
      recent evidence and tentative guidelines for online vaccine communication.

PMID- 22472791
TI  - Assessment of the immunogenicity and safety of varying doses of an MF59(r)
      adjuvanted cell culture-derived A/H1N1 pandemic influenza vaccine in Japanese
      paediatric, adult and elderly subjects.
AB  - INTRODUCTION: Effective vaccination strategies are required to combat future
      influenza pandemics. Here we report the results of three independent clinical
      trials performed in Japan to assess the immunogenicity, tolerability and safety
      of varying doses of a cell culture-derived MF59((r))-adjuvanted A/H1N1 pandemic
      vaccine in healthy Japanese paediatric, adult and elderly subjects. METHODS: One
      hundred and twenty-three children (6 months-18 years), and 200 adults (19-60
      years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine
      containing either 7.5 MUg antigen with a full (9.75 mg) adjuvant dose, or 3.75
      MUg antigen with a half (4.875 mg) adjuvant dose. One hundred elderly (>= 61
      years) subjects received only the low antigen/adjuvant vaccine formulation.
      Immunogenicity was assessed by haemagglutination inhibition assay at baseline and
      three weeks after the first and second vaccine doses on Days 22 and 43,
      respectively. Solicited and unsolicited adverse reactions were recorded for seven
      and 21 days post-immunization, respectively. RESULTS: In adult and elderly
      subjects, a single low antigen/adjuvant dose vaccination was sufficient to meet
      all of the three European licensure criteria established for influenza vaccines.
      One high, or two low antigen/adjuvant dose vaccinations were required to meet the
      licensure criteria in paediatric subjects. Both vaccine formulations were well
      tolerated, with the majority of adverse reactions mild to moderate in severity.
      None of the five serious adverse events reported throughout the three trials were
      considered to be vaccine-related by the investigators. CONCLUSION: The use of
      MF59 adjuvant allows for much reduced vaccine antigen content, and a single dose
      administration schedule in adults and the elderly. The production of pandemic
      vaccine using modern cell culture techniques is highly advantageous in terms of
      the quantity, quality, and rapidity of antigen production; these benefits, in
      combination with the use of MF59, maximize manufacturing capacity and global
      vaccine supply. These data support the suitability of the investigational vaccine
      for use in the Japanese paediatric, adult, and elderly populations.

PMID- 22472792
TI  - Effectiveness of the 2010-11 seasonal trivalent influenza vaccine in Spain:
      cycEVA study.
AB  - BACKGROUND: In Spain, the influenza vaccine effectiveness (VE) was estimated in
      the last three seasons using an observational study (cycEVA) conducted in the
      frame of the Spanish Influenza Sentinel Surveillance System. We aimed to measure
      the effectiveness of the seasonal trivalent vaccine in preventing influenza like
      illness (ILI) laboratory-confirmed influenza infection at the end of the season
      2010-11. METHODS: We conducted a test-negative case-control study between weeks
      50/2010 and 12/2011. Cases were ILI laboratory-confirmed influenza infection and
      controls were those testing negative. Sentinel physicians collected data on
      demographic and clinical characteristics, vaccination status, and on covariates
      related to confounding factors associating with influenza VE. We calculated
      adjusted odds ratios (OR), using logistic regression and computed influenza VE as
      (1-OR) * 100. RESULTS: The adjusted influenza VE against A(H1N1)pdm09 infection
      was 46% (95% confidence interval (95%CI): 0; 72). In A(H1N1)pdm09 infected
      patients who had received both 2010-11 trivalent influenza seasonal and 2009
      monovalent pandemic vaccines, influenza VE was 74% (95%CI: 13; 93). The adjusted
      influenza VE against B infection was 23% (95%CI: -180; 79). CONCLUSION: The
      trivalent influenza vaccine 2010-11 showed a moderate VE for preventing ILI
      laboratory confirmed influenza infections. Influenza VE estimates were higher in
      patients who had received both 2010-11 seasonal trivalent and 2009 monovalent
      pandemic vaccines.

PMID- 22472793
TI  - Baseline hepatitis B vaccination coverage among persons with diabetes before
      implementing a U.S. recommendation for vaccination.
AB  - BACKGROUND: Recent data suggest that adults with diabetes are at increased risk
      of incident hepatitis B infection and may suffer increased morbidity or mortality
      from chronic hepatitis B infection. In October 2011, the Advisory Committee on
      Immunization Practices (ACIP) recommended hepatitis B vaccination (HepB) for
      persons with diabetes aged 19-59 years and stated that persons with diabetes aged
      60 years and older should be considered for vaccination. OBJECTIVE: To determine
      HepB coverage among persons with diabetes aged >=19 years prior to implementation
      of the new ACIP recommendation and to determine predictors for vaccination.
      METHODS: We used the 2009 National Health Interview Survey to determine weighted
      proportions of self-reported HepB coverage (>=1 and >=3 doses) among persons with
      diabetes aged >=19 years. A multivariable logistic regression analysis was
      performed to determine factors independently associated with vaccination.
      RESULTS: Overall, 19.5% (95% CI: 17.4-21.6%) and 16.6% (14.7-18.6%) of persons
      with diabetes, aged >=19 years, reported receiving >=1 and >=3 doses of HepB,
      respectively, compared with 30.3% (29.4-31.3%) and 26.5% (25.5-27.4%) among
      persons without diabetes. While unadjusted HepB coverage was higher among persons
      without diabetes, diabetes status was not associated with >=1 or >=3 dose
      vaccination. Among persons with diabetes, being a healthcare provider (OR 4.2,
      2.5-7.0), ever tested for HIV (OR 2.6, 1.8-3.6), high-risk behaviors (OR 1.8, 1.0
      3.4, P-value=0.053) and having some college education (OR 1.7, 1.2-2.4) were all
      independently associated with vaccination. CONCLUSION: HepB coverage among
      persons with diabetes is low. These data can be used to provide a baseline for
      measuring future progress toward vaccination of persons with diabetes.

PMID- 22472794
TI  - Ginsenosides Rg1 and Re act as adjuvant via TLR4 signaling pathway.
AB  - Previous studies have demonstrated that ginsenosides Rg1 and Re extracted from
      the root of Panax ginseng C.A. Meyer have adjuvant properties. However, the
      molecular mechanisms behind their adjuvant activities remain unclear. In the
      present study, we first investigated the adjuvant effect of Rg1 and Re on the
      immune responses to a model antigen ovalbumin (OVA) in C3H/HeB mice as well as in
      C3H/HeJ mice carrying a defective toll-like receptor-4 (TLR4) gene, and then
      evaluated Rg1 and Re for their stimulation of phosphorylation of nuclear factor
      kappa B (NF-kappaB) p65 in the macrophages from above two different strains of
      mice. In addition, Rg1 and Re were also evaluated for their induction of NF
      kappaB in RAW-BlueTM cells. The results showed that Rg1 and Re had adjuvant
      activities in stimulating IgG, splenocyte proliferation, and mRNA expression of
      cytokines IL-4, IL-10, IL-12 and IFN-gamma as well as transcription factors GATA
      3 and T-bet by splenocytes in C3H/HeB mice but not in C3H/HeJ mice. Rg1 and Re
      induced phosphorylation of NF-kappaB p65 at Ser536 in macrophages from C3H/HeB
      mice but not from C3H/HeJ mice. Both Rg1 and Re induced expression of NF-kappaB
      in RAW-BlueTM cells. These results suggested that TLR4 signaling pathway is
      involved in the adjuvant activities of Rg1 and Re. Nevertheless, pretreatment
      with anti-TLR4 antibody suppressed the Re- but not Rg1-induced expression of NF
      kappaB, indicating that Rg1 may trigger both extracellular and intracellular TLR4
      by passing through the cell membrane while Re only activate extracellular TLR4 as
      it fails to enter inside of the cells to stimulate intracellular TLR4.

PMID- 22472796
TI  - Determination of infarct size in ex vivo swine hearts by multidetector computed
      tomography using gadolinium as contrast medium.
AB  - OBJECTIVE: To demonstrate the feasibility of using multidetector computed
      tomography with gadolinium contrast (Gd-MDCT) for the quantification of
      myocardial infarct (MI). MATERIALS AND METHODS: MI was induced in male swine (n =
      6). One week later, the animals received 0.2-mmol/kg gadopentetate dimeglumine
      and were sacrificed. On the excised hearts, Gd-MDCT with several tube voltages
      (80, 120, and 140 kV), late gadolinium enhancement MRI (LGE-MRI), and triphenyl
      tetrazolium-chloride staining were then conducted. We used a 2-SD threshold for
      the CT images and several threshold limits (2, 3, 4, 5, 6 SD, and full width at
      half-maximum [FWHM]) for the LGE-MRI images to delineate the infarct area. Total
      infarct volume and infarct fraction of each heart were calculated. RESULTS: MI
      size measured by MDCT at 140 kV showed good correlation with the reference
      triphenyl-tetrazolium-chloride value. Applying an 80-kV tube voltage, however,
      significantly underestimated MI size. In our study, the LGE-MRI method, using the
      6-SD threshold, provided the most accurate determination of MI size. LGE-MRI,
      using the 2- and 3-SD threshold limits, significantly overestimated infarct size.
      CONCLUSIONS: The Gd-MDCT technique has been found suitable for the evaluation of
      MI in an ex vivo experimental setting. Gd-MDCT has the ability to detect MI even
      at low kV settings, but accuracy is limited by a high image noise because of
      reduced photon flux.

PMID- 22472797
TI  - Virtual monochromatic spectral imaging for the evaluation of hypovascular hepatic
      metastases: the optimal monochromatic level with fast kilovoltage switching dual
      energy computed tomography.
AB  - OBJECTIVES: The purpose of this study was to select the optimal monochromatic
      level for virtual monochromatic spectral (VMS) imaging to minimize the image
      noise of the liver parenchyma and to acquire a high contrast-to-noise ratio (CNR)
      of hypovascular hepatic metastases in the portal-dominant phase. MATERIALS AND
      METHODS: This study was conducted with the approval of our institutional review
      board, and written informed consent was obtained from all the participating
      patients. Ninety patients with hepatic metastases were scanned by fast
      kilovoltage switching dual-energy computed tomography in the portal-dominant
      phase. One hundred one sets of VMS images in the range of 40 to 140 keV at 1-keV
      intervals were reconstructed. The image noise of the liver parenchyma in each
      patient and the CNR of each metastasis (n = 303) were measured on all the 101 VMS
      image sets. Data were analyzed by the paired t test and mixed-effects model.
      Bonferroni's method was used for multiple comparisons. RESULTS: The lowest noise
      of the liver parenchyma was obtained in 6, 15, 31, 29, 7, 1, and 1 patient at 67,
      68, 69, 70, 71, 72, and 73 keV, respectively. The mean noise of the liver
      parenchyma on the 69-keV VMS images in all 90 patients was significantly lower
      than that on the 67-, 68-, 71-, 72-, and 73-keV VMS images (P < 0.001); however,
      there was no significant difference in the mean noise of the liver parenchyma
      between the 69-keV and 70-keV VMS images (P = 0.279). For 95% of the hepatic
      metastases (288/303 metastases), the highest metastasis-to-liver CNR was obtained
      in the 66- to 71- keV VMS images. The mean metastasis-to-liver CNR for the 303
      metastases was numerically highest at 68 keV; however, there was no significant
      difference in the mean metastasis-to-liver CNR between the 68-keV and 69-keV
      images (P = 0.737) or between the 68-keV and 70-keV images (P = 0.103).
      CONCLUSIONS: VMS imaging at approximately 70 keV (69-70 keV) yielded the lowest
      image noise of the liver parenchyma and a high CNR for hypovascular hepatic
      metastases in the portal-dominant phase.

PMID- 22472798
TI  - Parametric diffusion tensor imaging of the breast.
AB  - OBJECTIVES: To investigate the ability of parametric diffusion tensor imaging
      (DTI), applied at 3 Tesla, to dissect breast tissue architecture and evaluate
      breast lesions. MATERIALS AND METHODS: All protocols were approved and a signed
      informed consent was obtained from all subjects. The study included 21 healthy
      women, 26 women with 33 malignant lesions, and 14 women with 20 benign lesions.
      Images were recorded at 3 Tesla with a protocol optimized for breast DTI at a
      spatial resolution of 1.9 * 1.9 * (2-2.5) mm3. Image processing algorithms and
      software, applied at pixel resolution, yielded vector maps of prime diffusion
      direction and parametric maps of the 3 orthogonal diffusion coefficients and of
      the fractional anisotropy and maximal anisotropy. RESULTS: The DTI-derived vector
      maps and parametric maps revealed the architecture of the entire mammary
      fibroglandular tissue and allowed a reliable detection of malignant lesions.
      Cancer lesions exhibited significantly lower values of the orthogonal diffusion
      coefficients, lambda1, lambda2, lambda3, and of the maximal anisotropy index
      lambda1-lambda3 as compared with normal breast tissue (P < 0.0001) and to benign
      breast lesions (P < 0.0009 and 0.004, respectively). Maps of lambda1 exhibited
      the highest contrast-to-noise ratio enabling delineation of the cancer lesions.
      These maps also provided high sensitivity/specificity of 95.6%/97.7% for
      differentiating cancers from benign lesions, which were similar to the
      sensitivity/specificity of dynamic contrast-enhanced magnetic resonance imaging
      of 94.8%/92.9%. Maps of lambda1-lambda3 provided a secondary independent
      diagnostic parameter with high sensitivity of 92.3%, but low specificity of 69.5%
      for differentiating cancers from benign lesions. CONCLUSION: Mapping the
      diffusion tensor parameters at high spatial resolution provides a potential novel
      means for dissecting breast architecture. Parametric maps of lambda1 and lambda1
      lambda3 facilitate the detection and diagnosis of breast cancer.

PMID- 22472799
TI  - Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2
      expression predicts the lack of biochemical response of somatotropinomas to
      treatment with somatostatin analogs.
AB  - OBJECTIVES: To evaluate somatostatin receptor 2A (SSTR2A) and dopamine receptor 2
      (DR2) protein expression in somatotropinomas and to relate it to response to
      somatostatin analogues (SA). DESIGN AND PATIENTS: SSTR2A and DR2 expression was
      analyzed by immunohistochemistry in 88 somatotropinomas from patients submitted
      to either pre-surgical or adjuvant SA treatment. Tumors were scored according to
      percentage of immunostained cells: 0 (< 25%), 1 (25-50%), and 2 (> 50%). Relation
      between protein expression and response to SA was performed in 66 patients.
      Response to SA was assessed by percent IGF-I reduction, being considered as an
      IGF-I per cent reduction higher than 50%. Disease control was also assessed (GH <
      1.0 ng/ml and normal IGF-I). RESULTS: SSTR2A and DR2 were expressed in 100% and
      98% of tumors, respectively. Biochemical response and disease control rates were
      48% and 32%, respectively. Median IGF-I percent reduction after 3 months of SA
      treatment was lower in the SSTR2A score 0 than in the scores 1 and 2 (p < 0.001,
      both), and after 6 months in the score 0 than in the score 1 (p = 0.001) and 2 (p
      < 0.001). Biochemical response and disease control were associated with SSTR2
      expression (p < 0.001 and p = 0.004, respectively). A negative predictive value
      for biochemical response of 100% was found when a SSTR2A expression < 25%of
      immunostained cells cut-off point was considered. No relation was found between
      DR2 expression and biochemical response and disease control. CONCLUSION: SSTR2A
      and DR2 are highly expressed in somatotropinomas. Low SSTR2A, but not DR2,
      expression is a negative predictive factor to response to SA.

PMID- 22472800
TI  - Frontostriatal connectivity in children during working memory and the effects of
      prenatal methamphetamine, alcohol, and polydrug exposure.
AB  - Various abnormalities in frontal and striatal regions have been reported in
      children with prenatal alcohol and/or methamphetamine exposure. In a recent fMRI
      study, we observed a correlation between accuracy on a working-memory task and
      functional activation in the putamen in children with prenatal methamphetamine
      and polydrug exposure. Because the putamen is part of the corticostriatal motor
      loop whereas the caudate is involved in the executive loop, we hypothesized that
      a loss of segregation between distinct corticostriatal networks may occur in
      these participants. The current study was designed to test this hypothesis using
      functional connectivity MRI. We examined 50 children ranging in age from 7 to 15,
      including 19 with prenatal methamphetamine exposure (15 of whom had concomitant
      prenatal alcohol exposure), 13 with prenatal exposure to alcohol but not
      methamphetamine, and 18 unexposed controls. We measured the coupling between
      blood oxygenation level dependent (BOLD) fluctuations during a working-memory
      task in four striatal seed regions and those in the rest of the brain. We found
      that the putamen seeds showed increased connectivity with frontal brain regions
      involved in executive functions while the caudate seeds showed decreased
      connectivity with some of these regions in both groups of exposed subjects
      compared to controls. These findings suggest that localized brain abnormalities
      resulting from prenatal exposure to alcohol and/or methamphetamine lead to a
      partial rewiring of corticostriatal networks. These results represent important
      progress in the field, and could have substantial clinical significance in
      helping devise more targeted treatments and remediation strategies designed to
      better serve the needs of this population.

PMID- 22472801
TI  - Sensitizing and Th2 adjuvant activity of cysteine protease allergens.
AB  - BACKGROUND: Innate properties that enhance immune responses might increase the
      propensity of certain allergens to induce allergic sensitization. Either a direct
      adjuvant effect or the increased immune response to the allergen could then
      increase allergic responses to bystander antigens. Here, we report on a model
      that does not use Th2-skewing adjuvants and yet achieves sensitization solely via
      the nasal mucosa. METHODS: Animals were sensitized with either enzymatically
      active, inactive or non-activated cysteine proteases via the nasal mucosa.
      Following two sensitization phases, mice were challenged with a higher dose of
      allergen. For bystander sensitization, mice received recombinant Der p 2 at
      sensitization in conjunction with the cysteine protease and were challenged with
      rDer p 2 alone. Sensitization was determined by measuring allergen-specific
      antibody responses and cytokine and cellular infiltrates into the lungs following
      challenge. RESULTS: Sensitization for Th2-type lung hypersensitivity for both the
      cysteine protease and bystander antigens was readily achieved and both were
      dependent on the proteolytic activity of the allergen. Bystander adjuvant
      activity was demonstrated for mice that were low IgE responders to the cysteine
      protease, showing a response independent from the immune response to the
      enhancing cysteine protease. Airway hyperreactivity was induced in the
      susceptible NOD strain of mouse, and mice subjected to prolonged administration
      of papain maintained the ability to produce lung hypersensitivity and Th2-type
      responses. CONCLUSIONS: These experiments demonstrate that cysteine protease
      activity at low doses can be an adjuvant for respiratory Th2 responses for
      themselves and bystander antigens in the absence of another adjuvant.

PMID- 22472802
TI  - Cardiovascular disease mortality among British asbestos workers (1971-2005).
AB  - OBJECTIVES: Asbestos is an inflammatory agent, and there is evidence that
      inflammatory processes are involved in the development of cardiovascular disease.
      Whether asbestos is a risk factor for cardiovascular disease has not been
      established. The objective of this study was to investigate cardiovascular
      disease mortality in a large cohort of workers occupationally exposed to
      asbestos. METHODS: Cardiovascular disease mortality in a cohort of 98,912
      asbestos workers, with median follow-up of 19 years, was analysed. Unadjusted and
      smoking-adjusted standardised mortality ratios (SMRs) were calculated. The
      association between indicators of asbestos exposure and mortality was analysed
      with Poisson regression models, for deaths occurring during the period 1971-2005.
      RESULTS: Altogether 15,557 deaths from all causes, 1053 deaths from
      cerebrovascular disease and 4185 deaths from ischaemic heart disease (IHD)
      occurred during follow-up. There was statistically significant excess mortality
      from cerebrovascular disease (SMR: men 1.63, women 2.04) and IHD (SMR: men 1.39,
      women 1.89). Job and birth cohort were associated with the risk of
      cerebrovascular and IHD mortality in the Poisson regression model including sex,
      age, smoking status, job, cohort and duration of exposure. For IHD only, duration
      of exposure was also statistically significant in this model. CONCLUSIONS:
      Cerebrovascular and IHD mortality was significantly higher among these asbestos
      workers than in the general population and within the cohort mortality was
      associated with indicators of asbestos exposure. These findings provide some
      evidence that occupational exposure to asbestos was associated with
      cardiovascular disease mortality in this group of workers.

PMID- 22472803
TI  - Quantitative MRI and cerebrospinal fluid inflammatory mediators in Brazilian
      patients with relapsing-remitting multiple sclerosis before and after treatment
      with immunomodulators: a longitudinal study.
AB  - OBJECTIVE: The pathological hallmarks of multiple sclerosis (MS) lesions are
      inflammation, demyelination, axon loss and gliosis. The aim of this study was to
      verify the relation of brain lesion load and volume of the cerebral hemisphere
      determined by brain MRI with intrathecal antibody synthesis. METHODS: A
      longitudinal study of 54 Brazilian patients with the relapsing-remitting form of
      MS was undertaken after an average of 6.3 +/- 2.7 years of treatment. MRI scans
      were performed, and cerebrospinal fluid samples were collected both during the
      diagnostic process and after treatment with beta-interferon or glatiramer
      acetate. RESULTS: A positive correlation between the IgG index and total lesion
      volume was identified. Intrathecal IgG against Epstein-Barr virus (EBV) was
      observed in 21 patients. The number of contrast-enhanced lesions observed in
      these patients was correlated with intrathecal IgM synthesis. Brain atrophy was
      observed early in the disease, with the number of relapses inversely correlated
      with brain volume. CONCLUSION: The high intrathecal IgG synthesis observed in
      these relapsing-remitting MS patients is associated with the brain lesion burden
      and the presence of antibodies to EBV, whereas intrathecal IgM synthesis is
      associated with the activity of the disease, as revealed by MRI.

PMID- 22472804
TI  - The relationship between concave angle of vertebral endplate and lumbar
      intervertebral disc degeneration.
AB  - STUDY DESIGN: A retrospective study of magnetic resonance imaging of the lower
      lumbar spine. OBJECTIVE: To describe the characteristics of the concave angle of
      vertebral endplate (CAVE) and study the association between CAVE and lumbar
      intervertebral disc degeneration (IVDD). SUMMARY OF BACKGROUND DATA: The
      vertebral endplate is responsible for transferring stress between disc and
      vertebral body, and its concavity is important in dispersing compression stress.
      However, the characteristics of CAVE and the relationship between CAVE and IVDD
      have not been investigated. METHODS: Magnetic resonance images of the lower
      lumbar spine in 511 patients with low back pain were examined by 2 experienced
      spine surgeons. The grades of IVDD and lumbar disc herniation (LDH) were
      evaluated, several parameters including CAVE, height, and the sagittal diameter
      of vertebral body were measured, and the association between IVDD or LDH and CAVE
      was analyzed. RESULTS: At L3-L4, L4-L5, and L5-S1, CAVE was smaller in the upper
      endplate (i.e., the inferior endplate of the superior vertebra) than in the lower
      endplate (i.e., the superior endplate of the inferior vertebra). There was no
      male/female difference in the size of CAVE in any of the segments. According to
      partial correlation analysis, CAVE was moderately related to IVDD, but no
      association between CAVE and LDH was found. CONCLUSION: When lumbar IVDD occurs,
      the CAVE increases and the endplate tends to flatten. The degree of flattening is
      related to the severity of the degeneration.

PMID- 22472805
TI  - Effect of biological agents on cervical spine lesions in rheumatoid arthritis.
AB  - STUDY DESIGN: A retrospective cohort analysis. OBJECTIVE: To determine the effect
      of biological agents (BAs) on the development and progression of cervical spine
      lesions and identify predictors of lesion progression. SUMMARY OF BACKGROUND
      DATA: The introduction of BAs has facilitated advances in the treatment of
      rheumatoid arthritis (RA). BAs reduce disease activity and limit structural joint
      damage. However, the effect of BAs on cervical spine lesions remains unclear.
      METHODS: Thirty-eight subjects who received more than 2 years of continuous BA
      treatment were enrolled. The mean x-ray interval was 4.4 years. RA activity was
      evaluated by disease activity score (DAS)-C reactive protein (CRP) and matrix
      metalloproteinase (MMP)-3. Radiographical definitions of cervical lesions were
      atlanto-dental interval (ADI) more than 3 mm for atlanto-axial subluxation (AAS),
      Ranawat value less than 13 mm for vertical subluxation (VS), and anterior or
      posterior listhesis more than 2 mm for subaxial subluxation (SS). Definitions of
      radiographical progression were an increase of ADI more than 2 mm for AAS, a
      decrease of both Ranawat and Redlund-Johnell values more than 2 mm for VS, and an
      increase of listhesis more than 2 mm for SS. RESULTS: RA activity responded
      dramatically to BA therapy (DAS-CRP from 4.3 to 2.3, P < 0.01; MMP-3 from 207.9
      ng/mL to 105.6 ng/mL, P < 0.01). Baseline radiographical evaluation showed no pre
      existing cervical spine lesions in 12 cases, AAS in 15 cases, and VS in 11 cases.
      Radiological progression was found in 1 (8%) patient in the no lesion group, 12
      patients (80%) in the AAS group, and 9 patients (80%) in the VS group. The
      incidence of progression was significantly lower in the no lesion group compared
      with the other groups. Multivariate regression analysis showed that the presence
      of pre-existing cervical lesions was the single greatest predictor of
      progression. CONCLUSION: BAs prevented the development of de novo cervical spine
      lesions in patients with RA, but failed to inhibit progression of pre-existing RA
      lesions.

PMID- 22472806
TI  - Spondylodiscitis as a spinal complication of transrectal ultrasound-guided needle
      biopsy of the prostate.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To describe the presentation of pyogenic
      spondylodiscitis as an iatrogenic spinal complication of a transrectal ultrasound
      guided needle biopsy of the prostate (TUGNBP), despite prophylactic use of
      antibiotics, and discuss possible route of infection. SUMMARY OF BACKGROUND DATA:
      Pyogenic spondylodiscitis is a rare complication of TUGNBP. Several similar case
      reports, have been previously published, including 1 by the authors of this case
      report; however, in the present case, spondylodiscitis occurred despite
      prophylactic antibiotic use. METHODS: A 59-year-old man was admitted to the
      neurosurgery department, experiencing severe back and bilateral leg pain for 6
      weeks. His neurological examination was normal. His medical and surgical
      histories were unremarkable, except for a TUGNBP performed 2 months ago because
      of the high serum levels of prostate-specific antigen levels. At the time of the
      biopsy, he had been given prophylactic oral antibiotic (ciprofloxacin, 500 mg
      twice a day) for 2 weeks. The day after biopsy, the patient experienced
      intermittent high fever and fatigue, and a week after biopsy, he complained of
      progressive back pain. RESULTS: After 2 weeks, whole-body bone scan with Tc99m
      MDP revealed hyperactivity at the level of L4 and L5 vertebral bodies. His
      contrast-enhanced magnetic resonance image of the lumbar spine showed diffuse
      contrast enhancement vertebral bodies and intervertebral disc of L4 and L5 along
      with contrast-enhanced circumferential epidural mass extending from S2 to L3
      levels. L4 hemilaminectomy and epidural and intradiscal abscess drainage at the
      L4-L5 levels were performed. The diagnosis was consistent with acute discitis
      with Gram (-) bacilli, and microbiological culture was positive for Escherichia
      coli. He received intravenous and oral antibiotics for 6 weeks. CONCLUSION: Acute
      pyogenic spondylodiscitis should be considered among the major complications of
      TUGNBP and may occur despite prophylactic antibiotic use.

PMID- 22472807
TI  - The impact of posture and prolonged cyclic compressive loading on vertebral joint
      mechanics.
AB  - STUDY DESIGN: An in vitro biomechanics investigation exposing porcine functional
      spinal units (FSUs) to submaximal cyclic or static compressive forces while in a
      flexed, neutral, or extended posture. OBJECTIVE: To investigate the combined
      effect of cyclically applied compressive force (e.g., vibration) and postural
      deviation on intervertebral joint mechanics. SUMMARY OF BACKGROUND DATA:
      Independently, prolonged vibration exposure and non-neutral postures are known
      risk factors for development of low back pain and injury. However, there is
      limited basic scientific evidence to explain how the risk of low back injury from
      vibration exposure is modified by other mechanical factors. This work examined
      the influence of static postural deviation on vertebral joint height loss and
      compressive stiffness under cyclically applied compressive force. METHODS: Forty
      eight FSUs, consisting of 2 adjacent vertebrae, ligaments, and the intervening
      intervertebral disc were included in the study. Each specimen was randomized to 1
      of 3 experimental posture conditions (neutral, flexed, or extended) and assigned
      to 1 of 2 loading protocols, consisting of (1) cyclic (1500 +/- 1200 N applied at
      5 Hz using a sinusoidal waveform, resulting in 0.2 g rms acceleration) or (2)
      1500 N of static compressive force. RESULTS.: As expected, FSU height loss
      followed a typical first-order response in both the static and cyclic loading
      protocols, with the majority (~50%) of the loss occurring in the first 20 minutes
      of testing. A significant interaction between posture and loading protocol (P <
      0.001) was noted in the magnitude of FSU height loss. Subsequent analysis of
      simple effects revealed significant differences between cyclic and static loading
      protocols in both a neutral (P = 0.016) and a flexed posture (P < 0.0001). No
      significant differences (P = 0.320) were noted between pre/postmeasurements of
      FSU compressive stiffness. CONCLUSION: Posture is an important mechanical factor
      to consider when assessing the risk of injury from cyclic loading to the lumbar
      spine.

PMID- 22472808
TI  - Retrograde ejaculation after anterior lumbar spine surgery.
AB  - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To compare the incidence
      of retrograde ejaculation (RE) after anterior lumbar spine surgery with disc
      replacement versus fusion with the use of recombinant human bone morphogenetic
      protein-2 (BMP). SUMMARY OF BACKGROUND DATA: Anterior lumbar interbody fusion
      (ALIF) has become a popular choice for treating a number of pathologies, largely
      because it preserves the posterior paravertebral muscles and ligaments. Despite
      these advantages, the anterior approach is also associated with various
      complications, one of which is RE. A recent study has questioned whether the risk
      of RE is increased by the use of BMP in ALIF procedures rather than by the
      approach alone. METHODS: We conducted a retrospective review of all male patients
      who received ALIF using BMP or artificial disc replacement (ADR) on at least the
      L5-S1 level between 2004 and 2011. Medical records were evaluated for the
      occurrence of RE, and patients were contacted via the phone to obtain current
      information. The incidence of RE was then compared between the 2 anterior lumbar
      surgery procedures. RESULTS: Of the 95 cases of anterior surgery including L5-S1,
      54 patients underwent ALIF with BMP (56.8%) and 41 patients were treated with ADR
      (43.2%). Postoperative RE occurred in 4 of the 54 ALIF patients (7.4%) and in 4
      of the 41 ADR patients (9.8%). The incidence of RE was not significantly
      different between groups (P = 0.7226). At latest follow-up, 1 ALIF and 1 ADR
      patient reported resolution of the RE. CONCLUSION: This study found that RE
      occurred at a similar rate in patients treated with ADR and ALIF with BMP. The
      overall rate of RE after retroperitoneal anterior lumbar surgery was higher than
      expected, which underscores the importance of counseling patients about this risk
      and specifically questioning patients about the symptoms of RE at postoperative
      visits.

PMID- 22472809
TI  - Multilevel analysis of trunk surface measurements for noninvasive assessment of
      scoliosis deformities.
AB  - STUDY DESIGN: Reliability study. OBJECTIVES: To assess between-acquisition
      reliability of new multilevel trunk cross sections measurements, in order to
      define what is a real change when comparing 2 trunk surface acquisitions of a
      same patient, before and after surgery or throughout the clinical monitoring.
      SUMMARY OF BACKGROUND DATA: Several cross-sectional surface measurements have
      been proposed in the literature for noninvasive assessment of trunk deformity in
      patients with adolescent idiopathic scoliosis (AIS). However, only the maximum
      values along the trunk are evaluated and used for monitoring progression and
      assessing treatment outcome. METHODS: Back surface rotation (BSR), trunk rotation
      (TR), and coronal and sagittal trunk deviation are computed on 300 cross sections
      of the trunk. Each set of 300 measures is represented as a single functional
      data, using a set of basis functions. To evaluate between-acquisition variability
      at all trunk levels, a test-retest reliability study is conducted on 35 patients
      with AIS. A functional correlation analysis is also carried out to evaluate any
      redundancy between the measurements. RESULTS: Each set of 300 measures was
      successfully described using only 10 basis functions. The test-retest reliability
      of the functional measurements is good to very good all over the trunk, except
      above the shoulders level. The typical errors of measurement are between 1.20
      degrees  and 2.2 degrees  for the rotational measures and between 2 and 6 mm for
      deviation measures. There is a very strong correlation between BSR and TR all
      over the trunk, a moderate correlation between coronal trunk deviation and both
      BSR and TR, and no correlation between sagittal trunk deviation and any other
      measurement. CONCLUSION: This novel representation of trunk surface measurements
      allows for a global assessment of trunk surface deformity. Multilevel trunk
      measurements provide a broader perspective of the trunk deformity and allow a
      reliable multilevel monitoring during clinical follow-up of patients with AIS and
      a reliable assessment of the esthetic outcome after surgery.

PMID- 22472810
TI  - Radiation exposure to the spine surgeon in lumbar and thoracolumbar fusions with
      the use of an intraoperative computed tomographic 3-dimensional imaging system.
AB  - STUDY DESIGN: A prospective clinical research article. OBJECTIVE: The primary
      goals were to determine (1) radiation exposure to the spine surgeon with the use
      of an intraoperative 3-dimensional imaging system and (2) to define the safe
      distance from the computed tomographic scanner. SUMMARY OF BACKGROUND:
      Intraoperative radiation exposure to the spinal surgeon has been assessed during
      2-dimensional fluoroscopy but has not been investigated during intraoperative 3
      dimensional imaging. METHODS: Ten patients undergoing lumbar or thoracolumbar
      fusion were enrolled in a prospective trial to determine the radiation exposure
      to a spine surgeon standing in the substerile room, with the use of the O-ARM
      Imaging System (Medtronic, Memphis, TN). A thermolucent digital dosimeter was
      worn at chest level without a lead apron. Dosimeter readings and distance from
      the spine surgeon were recorded. RESULTS.: Average surgeon exposure was 44.22 +/-
      17.4 MUrem (range: 17.71-70.76 MUrem). The mean distance from the O-ARM was 4.56
      +/- .32 m, and the surgeon was exposed for an average of 19.6 +/- 5.7 seconds
      (range: 8.05-28.7 s). The annual number of necessary procedures required to
      surpass the exposure limit, according to the data presented here, would be
      113,071 operations using O-ARM. Hence, the number of necessary procedures for O
      ARM use is predicted to be 1,130,710 annual procedures to reach the occupational
      exposure limits for extremity, skin, and all other organs and 339,213 procedures
      to reach the limits for the lens of eye. CONCLUSION: Radiation exposure is
      minimal to the surgical team during routine use of the O-ARM imaging system. The
      number of procedures required to surpass occupational exposure limits is high if
      using appropriate distance from the O-ARM.

PMID- 22472812
TI  - Exact analytical approach for six-degree-of-freedom measurement using image
      orientation-change method.
AB  - An exact analytical approach is proposed for measuring the six-degree-of-freedom
      (6-DOF) motion of an object using the image-orientation-change (IOC) method. The
      proposed measurement system comprises two reflector systems, where each system
      consists of two reflectors and one position sensing detector (PSD). The IOCs of
      the object in the two reflector systems are described using merit functions
      determined from the respective PSD readings before and after motion occurs,
      respectively. The three rotation variables are then determined analytically from
      the eigenvectors of the corresponding merit functions. After determining the
      three rotation variables, the order of the translation equations is downgraded to
      a linear form. Consequently, the solution for the three translation variables can
      also be analytically determined. As a result, the motion transformation matrix
      describing the 6-DOF motion of the object is fully determined. The validity of
      the proposed approach is demonstrated by means of an illustrative example.

PMID- 22472811
TI  - Rabbit notochordal cells modulate the expression of inflammatory mediators by
      human annulus fibrosus cells cocultured with activated macrophage-like THP-1
      cells.
AB  - STUDY DESIGN: We evaluated the influence of rabbit notochordal cells on the
      expression of inflammatory mediators by human annulus fibrosus (AF) cells
      cocultured with macrophage-like cells. OBJECTIVE: To identify the protective
      effect of rabbit notochordal cells on AF during in vitro inflammation. SUMMARY OF
      BACKGROUND DATA: Discogenic pain, which is an important cause of intractable
      lower back pain, is associated with macrophage-mediated inflammation in the AF.
      Although rabbit notochordal cells prevent intervertebral disc degeneration, their
      effects on human AF inflammation remain unknown. METHODS: Human AF pellets were
      cocultured for 48 hours with notochordal cell clusters from adult New Zealand
      White rabbits and phorbol myristate acetate (PMA)-stimulated human macrophage
      like THP-1 cells. Conditioned media (CM) from the cocultures were assayed by
      enzyme-linked immunosorbent assay. The expression of inflammatory mediators in
      the AF pellets was evaluated by real-time reverse-transcription polymerase chain
      reaction. RESULTS: The levels of mRNA for interleukin (IL)-6, IL-8, and inducible
      nitric oxide synthase (iNOS) in the AF pellets cocultured with notochordal cells
      and macrophages (hAF[rNC-M]) were significantly lower than those in the AF
      pellets cultured with macrophages alone (hAF[M]) (P < 0.05). The levels of IL-6
      and IL-8 proteins in the CM of hAF(rNC-M) were significantly lower than those in
      the CM of hAF(M) (P < 0.05). Coculturing with notochordal cells significantly
      decreased the levels of mRNA for IL-6, IL-8, and iNOS in the macrophage-exposed
      AF pellets (P < 0.05). After 1 ng/mL IL-1beta stimulation, the levels of IL-6 and
      IL-8 mRNA and the level of IL-8 protein production were significantly decreased
      in the AF pellets with notochordal cells compared with naive AF pellets (P <
      0.05). CONCLUSION: In an in vitro coculture system, rabbit notochordal cells
      reduced the levels of main inflammatory mediators and gene expression in the
      human AF during inflammation. Therefore, rabbit notochordal cells may constitute
      an important protective tool against symptomatic disc development.

PMID- 22472813
TI  - A computational inverse diffraction grating problem.
AB  - Consider the diffraction of a time-harmonic plane wave incident on a perfectly
      reflecting periodic surface. A continuation method on the wavenumber is developed
      for the inverse diffraction grating problem, which reconstructs the grating
      profile from measured reflected waves a constant distance away from the
      structure. Numerical examples are presented to show the validity and efficiency
      of the proposed method.

PMID- 22472814
TI  - General description of polarization in lidar using Stokes vectors and polar
      decomposition of Mueller matrices.
AB  - Polarization measurements have become nearly indispensible in lidar cloud and
      aerosol studies. Despite polarization's widespread use in lidar, its theoretical
      description has been widely varying in accuracy and completeness. Incomplete
      polarization lidar descriptions invariably result in poor accountability for
      scatterer properties and instrument effects, reducing data accuracy and
      disallowing the intercomparison of polarization lidar data between different
      systems. We introduce here the Stokes vector lidar equation, which is a full
      description of polarization in lidar from laser output to detector. We then
      interpret this theoretical description in the context of forward polar
      decomposition of Mueller matrices where distinct polarization attributes of
      diattenuation, retardance, and depolarization are elucidated. This decomposition
      can be applied to scattering matrices, where volumes consisting of randomly
      oriented particles are strictly depolarizing, while oriented ice crystals can be
      diattenuating, retarding, and depolarizing. For instrument effects we provide a
      description of how different polarization attributes will impact lidar
      measurements. This includes coupling effects due to retarding and depolarization
      attributes of the receiver, which have no description in scalar representations
      of polarization lidar. We also describe how the effects of polarizance in the
      receiver can result in nonorthogonal polarization detection channels. This
      violates one of the most common assumptions in polarization lidar operation.

PMID- 22472815
TI  - Phase singularities, correlation singularities, and conditions for complete
      destructive interference.
AB  - A previously derived condition for the complete destructive interference of
      partially coherent light emerging from a trio of pinholes in an opaque screen is
      generalized to the case when the coherence properties of the field are
      asymmetric. It is shown by example that the interference condition is necessary,
      but not sufficient, and that the existence of complete destructive interference
      also depends on the intensity of light emerging from the pinholes and the system
      geometry; more general conditions for such interference are derived. The phase of
      the wave field exhibits both phase singularities and correlation singularities,
      and a number of nonintuitive situations in which complete destructive
      interference occurs are described and explained.

PMID- 22472816
TI  - Influences of twist phenomenon of partially coherent field with uniform-intensity
      diffractive axicons.
AB  - The effects of twist phenomenon (beam rotation) of a partially coherent field are
      studied on the operation of two classes of uniform-intensity diffractive axicons.
      A general theory of axicon image formation is developed, discussed, and examined.
      We show that the intensity of the diffracted field is a multiple Bessel field,
      and only the energy of the zero-order Bessel field diffracts along the
      propagation axes. We also show that, at any twist strength in all correlation
      levels, the images can be evaluated by using the stationary-phase method. The
      three-dimensional stationary-phase formula of axicon images is derived. Such
      formula may be used in fast image evaluation, for designing diffractive axicons
      that perform a uniform axial intensity in a twisted partially coherent field.

PMID- 22472817
TI  - Broadband microwave Luneburg lens made of gradient index metamaterials.
AB  - Luneburg lenses are able to form perfect focus that is free of aberration.
      Because of the varying refractive index throughout the lens, incoming
      electromagnetic waves can travel in a curved path and be guided to focus at the
      back of the lens. The implementation of Luneburg lenses is often difficult due to
      the challenges in creating a medium with varying refractive index using normal
      materials. This problem can be overcome with the use of gradient index
      metamaterials. We report a two dimensional Luneburg lens made of gradient index
      metamaterials. It consists of 17 concentric shells with etched patterns on a
      printed circuit board working in microwave X band frequency. The broad properties
      of the Luneburg lens are then discussed.

PMID- 22472818
TI  - Phase-shifting algorithms for a finite number of harmonics: first-order analysis
      by solving linear systems.
AB  - From generalized phase-shifting equations, we propose a simple linear system
      analysis for algorithms with equally and nonequally spaced phase shifts. The
      presence of a finite number of harmonic components in the fringes of the
      intensity patterns is taken into account to obtain algorithms insensitive to
      these harmonics. The insensitivity to detuning for the fundamental frequency is
      also considered as part of the description of this study. Linear systems are
      employed to recover the desired insensitivity properties that can compensate
      linear phase shift errors. The analysis of the wrapped phase equation is carried
      out in the Fourier frequency domain.

PMID- 22472819
TI  - Pupil aberrations in Offner spectrometers.
AB  - The light path function (LPF) of an Offner spectrometer is presented. The
      evaluation of the LPF of this spectrometer enables its imaging properties to be
      studied for arbitrary object and image positions, while avoiding the more
      complicated analysis of intermediate images generated by the diffraction grating,
      which is often involved. A power series expansion of the LPF on the grating
      coordinates directly determines pupil aberrations of the generated spectrum and
      facilitates the search for configurations with small low-order aberrations. This
      analysis not only confirms the possibility of reducing low-order aberrations in
      Rowland-type mounts, namely astigmatism and coma, as predicted in previous
      studies, but also proves that all third-order terms in the series expansion of
      the aberration function can be canceled at the image of the design point and for
      the corresponding design wavelength, when the design point is located on a plane
      orthogonal to the optical axis. Furthermore, fourth-order terms are computed and
      shown to represent the most relevant contribution to image blurring. Third- and
      fourth-order aberrations are also evaluated for Rowland mounts with the design
      point located outside the aforementioned plane. The study described in this
      manuscript is not restricted to small angles of incidence, and, therefore, it
      goes beyond Seidel and Buchdahl aberrations.

PMID- 22472820
TI  - Combining diffuse optical tomography and spectroscopy to detect and characterize
      lesions in two-layered tissues.
AB  - We combine diffuse optical tomography for detecting and localizing an
      inhomogeneity in a two-layered tissue and diffuse optical spectroscopy (DOS) for
      characterizing the spectrum of that inhomogeneity. For detecting and localizing
      an inhomogeneity, we reduce the number of unknowns substantially by seeking only
      the location and size of the inhomogeneity. Then, we seek to recover an unknown
      specific tumor component of that inhomogeneity from spectral data. In doing so,
      we develop a method for distinguishing between healthy and tumorous lesions. We
      demonstrate the utility of this theory with numerical simulations.

PMID- 22472821
TI  - Droplet-shaped waves: causal finite-support analogs of X-shaped waves.
AB  - A model of steady-state X-shaped wave generation by a superluminal (supersonic)
      pointlike source infinitely moving along a straight line is extended to a more
      realistic causal scenario of a source pulse launched at time zero and propagating
      rectilinearly at a constant superluminal speed. In the case of an infinitely
      short (delta) pulse, the new model yields an analytical solution, corresponding
      to the propagation-invariant X-shaped wave clipped by a droplet-shaped support,
      which perpetually expands along the propagation and transversal directions, thus
      tending the droplet-shaped wave to the X-shaped one.

PMID- 22472822
TI  - Analogies between classical scalar wave fields in any state of spatial coherence
      and some quantum states of light.
AB  - The border between the descriptions of the classical optical fields in any state
      of spatial coherence and the quantum coherence state of light is revisited in the
      framework of the phase-space representation. Although it is established that such
      descriptions are not completely equivalent, the exact calculation of the marginal
      power spectrum leads to new analogies that suggest that some features exclusively
      attributed to quantum states of light can be also shared by classical optical
      fields due to their spatial coherence state.

PMID- 22472823
TI  - Electromagnetic field attractor made of gradient index metamaterials.
AB  - We present a device that is designed with varying permittivity epsilon(r) such
      that an electromagnetic wave in the K-band of the microwave regime entering it
      will bend inward towards the core. The core is made of silicon composites. We
      follow the distribution formula of the permittivity for the device derived by
      Narimanov and Kildishev using the optical-mechanical analogy. The diameter of the
      device is 14 cm, and it is constructed out of 21 rings of two different types of
      etched printed circuit boards, as well as dielectric powders as adding filling
      materials. The experimental wave intensity profile, based on parallel plate
      measurements for the cases where the incident plane wave is slightly displaced to
      the top of the center of the device and the case of on center incidence, are
      presented and discussed. In spite of some mismatch of the core and metamaterial
      structures of the device found, approximately 80% of the wave still manages to
      reach the core of the device and gets trapped and absorbed. Broadband properties
      of the device are also investigated.

PMID- 22472824
TI  - Sensitivity of synthetic aperture laser optical feedback imaging.
AB  - In this paper, we compare the sensitivity of two imaging configurations, both
      based on laser optical feedback imaging (LOFI). The first one is direct imaging,
      which uses conventional optical focalization on target, and the second one is
      made by a synthetic aperture (SA) laser, which uses numerical focalization. We
      show that SA configuration allows us to obtain good resolutions with high working
      distance and that the drawback of SA imagery is that it has a worse photometric
      balance in comparison to a conventional microscope. This drawback is partially
      compensated by the important sensitivity of LOFI. Another interest of SA relies
      on the capacity of getting three-dimensional information in a single x-y scan.

PMID- 22472825
TI  - Double refraction of a Gaussian beam into a uniaxial crystal.
AB  - For a linearly polarized three-dimensional Gaussian beam in air that is normally
      incident upon a plane interface with a uniaxial crystal with optic axis in an
      arbitrary direction, we present integral representations for the transmitted
      field suitable for asymptotic analysis and efficient numerical evaluation and
      derive analytical expressions for transmitted nontruncated Gaussian beams for the
      cases in which the incident beam is polarized parallel to the plane containing
      the optic axis and the interface normal and transverse to it. The general
      solution for an arbitrary polarization state of an incident Gaussian beam follows
      by superposition of these two solutions.

PMID- 22472826
TI  - High topographical accuracy by optical shot noise reduction in digital
      holographic microscopy.
AB  - In this work, we present a new method to reduce the shot noise in phase imaging
      of digital holograms. A spatial averaging process of phase images reconstructed
      at different reconstruction distances is performed, with the reconstruction
      distance range being specified by the numerical focus depth of the optical
      system. An improved phase image is attained with a 50% shot noise reduction. We
      use the integral of the angular spectrum as a reconstruction method to obtain a
      single-object complex amplitude that is needed to perform our proposal. We also
      show the corresponding simulations and experimental results. The topography of a
      homemade TiO2 stepwise of 100 nm high was measured and compared with the atomic
      force microscope results.

PMID- 22472827
TI  - Analysis of an optical resonator formed by a pair of specially shaped axicons.
AB  - We propose a design for an optical resonator suited to using large-bore active
      media. The resonator consists of a pair of waxicons, so we call it a "wwaxicon
      optical resonator." The resonator is considered a conventional (solid) resonator
      surrounded by coaxial annular resonators. A numerical simulation of the resonator
      designed for use in a commercial CO2 laser is performed. It is found that
      parasitic oscillation modes can be suppressed by the use of an spatial-frequency
      filter. The resonator exhibits oscillation in the TEM*01 transverse mode and
      produces twice as much output power as a sevenfold multipass stable optical
      resonator.

PMID- 22472828
TI  - Phase retrieval on annular and annular sector pupils by using the eigenfunction
      method to solve the transport of intensity equation.
AB  - Phase retrieval on an annular pupil and an annular sector pupil by using the
      eigenfunction method to solve the transport of intensity equation is proposed.
      The analytic expressions of Laplacian eigenfunctions with the Neumann boundary
      condition on an annular pupil and an annular sector pupil are given. The phase
      can be expanded as a set of eigenfunctions on the corresponding pupil, and the
      coefficients of the eigenfunctions can be obtained by the integral of the
      eigenfunction and the intensity derivative along the optical axis. Phase
      retrieval by the eigenfunction method on an annular pupil and an annular sector
      pupil is simulated, and accurate retrieved results are obtained.

PMID- 22472829
TI  - Mechanism and symmetry properties of depolarization in weak scattering of light.
AB  - The mechanism and some symmetry properties of depolarization upon weak scattering
      of light from a class of random media were studied theoretically. Departing from
      the angular distribution of the degree of polarization, our derivations showed
      the mechanism that induces the change of polarization can be split into two parts
      of different nature. One is the vectorial effect that redistributes the original
      light components, and the other is the interaction effect of the medium that
      modulates the correlation properties of the incident field. We also showed that
      there is dependence of the angular distribution on the incident polarization
      state; i.e., the angular pattern and its symmetry depend on both the orientation
      and ellipticity of the incident polarization. Random light was analyzed in the
      space-frequency domain.

PMID- 22472830
TI  - Three-dimensional resolvability in an integral imaging system.
AB  - The concept of three-dimensional (3D) resolvability of an integral imaging system
      is thoroughly investigated in this research. The general concept of 3D resolution
      fails to describe the 3D discrimination completely. Then the concepts of the
      depth-resolution plane and lateral-resolution plane are introduced to show the
      difference between the conventional 3D spatial resolution and the newly
      introduced 3D resolvability. Therefore, the different properties of these planes
      for differentiating lateral spatial variations and axial variations are analyzed
      in this paper. The theoretical statements are demonstrated experimentally.

PMID- 22472831
TI  - Rapid analysis of scattering from periodic dielectric structures using
      accelerated Cartesian expansions.
AB  - The analysis of fields in periodic dielectric structures arise in numerous
      applications of recent interest, ranging from photonic bandgap structures and
      plasmonically active nanostructures to metamaterials. To achieve an accurate
      representation of the fields in these structures using numerical methods, dense
      spatial discretization is required. This, in turn, affects the cost of analysis,
      particularly for integral-equation-based methods, for which traditional iterative
      methods require O(N2) operations, N being the number of spatial degrees of
      freedom. In this paper, we introduce a method for the rapid solution of
      volumetric electric field integral equations used in the analysis of doubly
      periodic dielectric structures. The crux of our method is the accelerated
      Cartesian expansion algorithm, which is used to evaluate the requisite potentials
      in O(N) cost. Results are provided that corroborate our claims of acceleration
      without compromising accuracy, as well as the application of our method to a
      number of compelling photonics applications.

PMID- 22472832
TI  - Modal dynamics in multimode fibers.
AB  - The dynamics of modes and their states of polarizations in multimode fibers as a
      function of time, space, and wavelength are experimentally and theoretically
      investigated. The results reveal that the states of polarizations are displaced
      in Poincare sphere representation when varying the angular orientations of the
      polarization at the incident light. Such displacements, which complicate the
      interpretation of the results, are overcome by resorting to modified Poincare
      sphere representation. With such modification it should be possible to predict
      the output modes and their state of polarization when the input mode and state of
      polarization are known.

PMID- 22472833
TI  - Photon diffusion in a homogeneous medium bounded externally or internally by an
      infinitely long circular cylindrical applicator. III. Synthetic study of
      continuous-wave photon fluence rate along unique spiral paths.
AB  - This is Part III of the work that examines photon diffusion in a scattering
      dominant medium enclosed by a "concave" circular cylindrical applicator or
      enclosing a "convex" circular cylindrical applicator. In Part II of this work
      Zhang et al. [J. Opt. Soc. Am. A, 66 (2011)] predicted that, on the tissue
      applicator interface of either "concave" or "convex" geometry, there exists a
      unique set of spiral paths, along which the steady-state photon fluence rate
      decays at a rate equal to that along a straight line on a planar semi-infinite
      interface, for the same line-of-sight source-detector distance. This phenomenon
      of steady-state photon diffusion is referred to as "straight-line-resembling
      spiral paths" (abbreviated as "spiral paths"). This Part III study develops
      analytic approaches to the spiral paths associated with geometry of a large
      radial dimension and presents spiral paths found numerically for geometry of a
      small radial dimension. This Part III study also examines whether the spiral
      paths associated with a homogeneous medium are a good approximation for the
      medium containing heterogeneity. The heterogeneity is limited to an anomaly that
      is aligned azimuthally with the spiral paths and has either positive or negative
      contrast of the absorption or scattering coefficient over the background medium.
      For a weak-contrast anomaly the perturbation by it to the photon fluence rate
      along the spiral paths is found by applying a well-established perturbation
      analysis in cylindrical coordinates. For a strong-contrast anomaly the change by
      it to the photon fluence rate along the spiral paths is computed using the finite
      element method. For the investigated heterogeneous-medium cases the photon
      fluence rate along the homogeneous-medium associated spiral paths is
      macroscopically indistinguishable from, and microscopically close to, that along
      a straight line on a planar semi-infinite interface.

PMID- 22472834
TI  - Veiling glare and perceived black in high dynamic range displays.
AB  - A perceptual experiment was conducted to measure the visibility of black-level
      differences in the proximity of a bright glare source. In a controlled viewing
      environment, visual difference thresholds were adaptively measured using dark,
      shadow-detail images shown on a high dynamic range liquid crystal display while
      an external LED lamp was used to induce intra-ocular glare over a small range of
      eccentricities. This high-contrast situation is relevant to high dynamic range
      displays that may have bright regions in displayed images, as well as to viewing
      environments that include lamps or other light sources. The resulting difference
      thresholds are modeled with a combination of the CIE total glare equation, the
      DICOM contrast visibility model, and a new estimate of adaptation luminance.

PMID- 22472835
TI  - From stationary annular rings to rotating Bessel beams.
AB  - In this work we use a phase-only spatial light modulator (SLM) to mimic a ring
      slit aperture, containing multiple azimuthally varying phases at different radial
      positions. The optical Fourier transform of such an aperture is currently known
      and its intensity profile has been shown to rotate along its propagation axis.
      Here we investigate the near-field of the ring-slit aperture and show, both
      experimentally and theoretically, that although the near-field possesses similar
      attributes to its Fourier transform, its intensity profile exhibits no rotation
      as it propagates.

PMID- 22472836
TI  - Extension of the Stokes equation for layered constructions to fluorescent turbid
      media.
AB  - Expressions relating the bispectral reflectance of a stack of n fluorescing
      layers to each individual layer's reflectance and transmittance are derived. This
      theoretical framework is used together with recently proposed extensions of the
      Kubelka-Munk model to study the fluorescence from layered turbid media. For one
      layer over a reflecting background, the model is shown to give the same results
      as a previous model. The extension to n layers with different optical properties
      allows simulating the bispectral reflectance from a pad of layered turbid media.
      The applicability of the model is exemplified with an optimization of fluorophore
      distribution in layered turbid media.

PMID- 22472837
TI  - Cross-polarization of linearly polarized Hermite-Gauss laser beams.
AB  - Evolution of transverse intensity profiles for the dominant and cross
      polarization components of linearly polarized Hermite-Gauss laser beams is
      studied experimentally as the beams propagate away from their waist. Measured
      intensity profiles and their evolution with propagation are in good agreement
      with the theoretical predictions.

PMID- 22472838
TI  - Focal-plane detection and object reconstruction in the noninterferometric phase
      imaging.
AB  - In this paper, we propose effective methods to detect focal planes and recover
      objects in the noninterferometric phase imaging. A strategy using different
      aberration coefficients is developed, and a series of diffraction intensity maps
      is sequentially recorded by a charge-coupled device. During numerical
      reconstruction, a phase retrieval algorithm is applied to extract object
      wavefront from diffraction intensity maps. Subsequently, numerical methods are
      proposed to detect focal planes, and high-quality phase maps are recovered by
      using the detected focal distances. Theoretical results are presented to
      demonstrate feasibility and effectiveness of the proposed methods.

PMID- 22472839
TI  - Field singularities at lossless metal-dielectric arbitrary-angle edges and their
      ramifications to the numerical modeling of gratings.
AB  - I extend a previous work [J. Opt. Soc. Am. A, 738 (2011)] on field singularities
      at lossless metal-dielectric right-angle edges and their ramifications to the
      numerical modeling of gratings to the case of arbitrary metallic wedge angles.
      Simple criteria are given that allow one knowing the lossless permittivities and
      the arbitrary wedge angles to determine if the electric field at the edges is
      nonsingular, can be regularly singular, or can be irregularly singular without
      calculating the singularity exponent. Furthermore, the knowledge of the
      singularity type enables one to predict immediately if a numerical method that
      uses Fourier expansions of the transverse electric field components at the edges
      will converge or not without making any numerical tests. All conclusions of the
      previous work about the general relationships between field singularities,
      Fourier representation of singular fields, and convergence of numerical methods
      for modeling lossless metal-dielectric gratings have been reconfirmed.

PMID- 22472840
TI  - Scattering of a pulsed wave by a sphere with an eccentric spherical inclusion.
AB  - A dielectric sphere with an eccentric spherical dielectric inclusion and an
      incident amplitude-modulated plane electromagnetic wave constitute an exterior
      radiation problem, which is solved in this paper. A solution is obtained by
      combined use of the Fourier transform and the indirect-mode-matching method. The
      analysis yields a set of linear equations for the wave amplitudes of the
      frequency-domain expansion of the electric-field intensity within and outside the
      externally spherical inhomogeneous body; that set is solved by truncation and
      matrix inversion. The shape of the backscattered pulse in the time domain is
      determined by application of the inverse fast Fourier transform. Numerical
      results are shown for a pulse backscattered by an acrylic sphere that contains an
      eccentric spherical cavity. The effects of cavity position and size on pulse
      spreading and delay are discussed.

PMID- 22472841
TI  - Compressive imaging of subwavelength structures: periodic rough surfaces.
AB  - A compressed sensing scheme for near-field imaging of corrugations of relative
      sparse Fourier components is proposed. The scheme employs random sparse
      measurement of near field to recover the angular spectrum of the scattered field.
      Surprisingly, it can be shown heuristically and numerically that under the
      Rayleigh hypothesis the angular spectrum is compressible and amenable to
      compressed sensing techniques. Iteration schemes are developed for recovering the
      surface profile from the angular spectrum. The proposed nonlinear least squares
      in the Fourier basis produces accurate reconstructions even when the Rayleigh
      hypothesis is known to be false.

PMID- 22472842
TI  - Photometric stereo applied to diffuse surfaces that violate Lambert's law.
AB  - This paper investigates the use of photometric stereo (PS) with reflectance
      functions that are diffuse but not Lambertian. We show that, for the special case
      where light sources are arranged at 90 degrees  intervals around the optical
      axis, standard PS is not limited to Lambertian surfaces, and we define criteria
      for its use. A series of rough test surfaces are used as models for surface
      microstructure-we found that the Oren Nayar (ON) reflectance model accurately
      predicted the surfaces' reflectance functions. The ON model does not meet our
      theoretical criteria for using PS, but PS performs well in simulations if the
      microroughness is moderate (rms slope <0.3). When PS was applied to real
      surfaces, the estimated and actual slopes were highly correlated, but there were
      significant errors in the slope estimates for the rougher samples.

PMID- 22472843
TI  - Graphics processing unit (GPU)-accelerated particle filter framework for positron
      emission tomography image reconstruction.
AB  - As a consequence of the random nature of photon emissions and detections, the
      data collected by a positron emission tomography (PET) imaging system can be
      shown to be Poisson distributed. Meanwhile, there have been considerable efforts
      within the tracer kinetic modeling communities aimed at establishing the
      relationship between the PET data and physiological parameters that affect the
      uptake and metabolism of the tracer. Both statistical and physiological models
      are important to PET reconstruction. The majority of previous efforts are based
      on simplified, nonphysical mathematical expression, such as Poisson modeling of
      the measured data, which is, on the whole, completed without consideration of the
      underlying physiology. In this paper, we proposed a graphics processing unit
      (GPU)-accelerated reconstruction strategy that can take both statistical model
      and physiological model into consideration with the aid of state-space evolution
      equations. The proposed strategy formulates the organ activity distribution
      through tracer kinetics models and the photon-counting measurements through
      observation equations, thus making it possible to unify these two constraints
      into a general framework. In order to accelerate reconstruction, GPU-based
      parallel computing is introduced. Experiments of Zubal-thorax-phantom data, Monte
      Carlo simulated phantom data, and real phantom data show the power of the method.
      Furthermore, thanks to the computing power of the GPU, the reconstruction time is
      practical for clinical application.

PMID- 22472844
TI  - Far-infrared properties of hybrid plasmonic geometries.
AB  - Plasmonic structures made of periodically arranged metallic rings integrated into
      subwavelength holes are investigated at the far-infrared terahertz frequencies.
      The emergence and the interplay of various resonances sustained by such plasmonic
      samples are elucidated. To reveal a coherent physical picture, relevant
      dimensions of the samples are modified and their impact on the resonance
      properties is analyzed. The experimental work is fully supported by numerical
      simulations. The understanding of the interplay of various resonances will foster
      applications which require plasmonic substrates to exhibit simultaneously
      resonances at well-defined frequencies and line widths.

PMID- 22472845
TI  - Is cognitive impairment following early life stress in severe mental disorders
      based on specific or general cognitive functioning?
AB  - Schizophrenia spectrum and bipolar disorder are characterized by high levels of
      childhood trauma as well as of cognitive dysfunction. Our aim is to investigate
      the association between these two factors in the largest study in the literature
      so far. A total of 406 patients with schizophrenia spectrum- or bipolar disorders
      were recruited from a catchment area based organization in Oslo, Norway.
      Information about early life stress was obtained using the Childhood Trauma
      Questionnaire (CTQ). Cognitive function was assessed through a comprehensive and
      standardized neuropsychological test battery. Physical abuse, sexual abuse and
      physical neglect were significantly associated with reduced scores on working
      memory and executive function scales (p=0.04 to p<0.001), and verbal and
      performance tasks from the Wechsler Abbreviated Scale of Intelligence (WASI)
      (p=0.059 to p<0.001). When verbal and performance tasks from the WASI were added
      into a multivariate regression model, the association between CTQ and the
      specific cognitive domains decreased, and only WASI scores remained statistically
      significant. Our results indicate that childhood trauma is associated with a
      reduction in cognitive function across cognitive domains in patients with
      schizophrenia spectrum- and bipolar disorders, in particular working memory and
      executive function as well as general cognition. Moreover, these dysfunctions
      seem to be driven by underlying deficits in general cognitive tasks as measured
      by the WASI.

PMID- 22472846
TI  - Single right coronary artery giving off anomalous origin of left anterior
      descending artery with diffuse myocardial bridge:  the role of computed
      tomography scan.
AB  - A 58-year-old woman who presented with resting chest pain underwent coronary
      angiography and multidetector computed tomography (MDCT), with detection of a
      single right coronary artery giving off an anomalous origin of the left anterior
      descending artery, subpulmonic type with diffuse myocardial bridge. The
      myocardial bridge was detected by MDCT, not by coronary angiography. Our findings
      suggest that MDCT has an important role in the more precise evaluation of
      clinical and anatomical information in patients with a single coronary artery.

PMID- 22472847
TI  - Percutaneous implantation of Edwards SAPIEN valve into pulmonary bioprosthesis
      (valve-in-valve).
AB  - We report the case of a 14-year-old boy affected by Tetralogy of Fallot and
      pulmonary atresia, who had already undergone multiple surgical procedures. He had
      later developed a steno-insufficiency of the pulmonary bioprosthesis. We
      performed a percutaneous pulmonary valve implantation (PPVI), which is a
      minimally invasive treatment, as effective as conventional valve surgery and
      associated with less morbidity and mortality. Up to now PPVI has been carried out
      in patients with chronic pulmonary vascular resistance (PVR) in the presence of a
      right ventricular outflow tract (RVOT) patch by prior deployment of an
      intravascular stent as an artificial conduit that makes subsequent valve
      implantation possible. The peculiarity of our procedure was that we implanted the
      valve directly on to the annulus of the bioprosthesis (valve-in-valve), without
      performing a prestenting of the prosthetic valve.

PMID- 22472848
TI  - Chronic total occlusion treatment as a health insurance: collateral
      recruitability and bidirectionality.

PMID- 22472849
TI  - A 'clover' coronary artery:  role of coronary computed tomography to indicate
      optimal treatment in aneurysmal coronary artery disease.
AB  - We report the case of a 61-year-old man referred to our department for exertional
      angina with a history of tri-vessel aneurysmal coronary artery disease. Exercise
      stress echocardiography was positive for inferior wall hypokinesia. Coronary
      computed tomography (CT) provided a more accurate characterization of the
      coronary aneurysms. It detected a laminated thrombus of the proximal left
      anterior descending and a clover-like aneurysmal dissection of the proximal right
      coronary artery, which questioned the feasibility of coronary angioplasty. So,
      the patient was treated with medical therapy only. This case confirmed the
      importance of coronary CT as diagnostic tool for procedural risk assessment and
      definition of the most appropriate treatment in patients with coronary aneurysms.

PMID- 22472850
TI  - B-type natriuretic peptide assessment in ambulatory heart failure patients: 
      insights from IMPROVE HF.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) levels provide diagnostic and
      prognostic information in heart failure. This study determined the frequency of
      BNP assessment and analyzed demographic characteristics, clinical variables and
      the utilization of guideline-recommended heart failure therapies by BNP level in
      outpatients with reduced left ventricular ejection fraction (LVEF). METHODS AND
      RESULTS: The IMPROVE HF registry (The Registry to Improve the Use of Evidence
      Based Heart Failure Therapies in the Outpatient Setting) is a prospective cohort
      study of patients at least 18 years of age with a LVEF 35% or less and chronic
      heart failure or previous myocardial infarction (MI) presenting to cardiology and
      multispecialty practices. The medical records of 15,381 patients were reviewed.
      BNP was measured in 4213 (27.4%) patients and the median plasma BNP level was 384
      pg/ml (interquartile range 158-877 pg/ml). Patients were stratified by plasma BNP
      measurements into the following tertiles: 219 pg/ml or less, more than 219 to 649
      pg/ml, and more than 649 pg/ml. Jugular venous distension, pedal edema, rales and
      systolic murmur on physical examination and elevated renal function parameters
      were associated with higher BNP levels. BNP assessment and elevated BNP levels
      were not associated with greater use of any of the quality of care measures.
      However, patients with a BNP in the top tertile were less likely to be treated
      with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or
      aldosterone antagonists compared with patients with a BNP in the bottom tertile.
      CONCLUSION: Among practices participating in IMPROVE HF, BNP was not measured in
      most outpatients with reduced LVEF and chronic heart failure or previous MI. BNP
      assessment or the BNP level in patients with recorded measurements, with few
      exceptions, did not impact the utilization of guideline-recommended therapies.

PMID- 22472851
TI  - Relationship between gastroesophageal junction adenocarcinoma and Helicobacter
      pylori infection in Japan.
AB  - BACKGROUND/AIMS: The relationship between gastroesophageal junction
      adenocarcinoma (GEJA) and Helicobacter pylori infection is not well defined;
      thus, we retrospectively investigated this relationship. METHODS: We examined 852
      cases (646 men) of gastric cancer. GEJA was defined as type II according to the
      classification system of Siewert and Stein. We compared the prevalence of H.
      pylori infection and corporal gastritis in GEJA patients with distal gastric
      cancer. RESULTS: GEJA was observed in 80 (including 6 cases of Barrett's
      esophageal cancer) of the 852 cases of gastric cancer examined (9.4%). The rate
      of H. pylori infection was significantly lower in patients with GEJA than in
      patients with distal gastric cancer (73.8 vs. 94.1%, p < 0.05). The prevalence of
      corporal gastritis was also significantly lower in patients with GEJA than in
      patients with distal gastric cancer (80.7 vs. 94.6%, p < 0.05). Concurrent H.
      pylori infection and corporal gastritis were not observed in patients with
      Barrett's esophageal cancer. CONCLUSION: Our study demonstrated that GEJA has 2
      etiologic types; one of these types is associated with H. pylori infection and
      resembles distal gastric cancer, and the other one is not associated with H.
      pylori infection or Barrett's esophageal cancer.

PMID- 22472852
TI  - Patterned recognition of amines and ammonium ions by a pyridine-based helical
      oligoamide host.
AB  - In response to binding to amine and ammonium guests of varying types, a pyridine
      based folding oligomer displays fingerprint regions in its (1)H NMR spectra that
      allow for the easy identification and classification of the bound guests.

PMID- 22472853
TI  - Candida and candidiasis in HIV-infected patients:  where commensalism,
      opportunistic behavior and frank pathogenicity lose their borders.
AB  - In this era of efficacious antiretroviral therapy and consequent immune
      reconstitution, oropharyngeal and esophageal candidiasis (OPC and OEC) still
      remain two clinically relevant presentations in the global HIV setting. Both
      diseases are predominantly caused by Candida albicans, a polymorphic fungus which
      is a commensal microbe in the healthy individual but can become an aggressive
      pathogen in a debilitated host. Actually, C. albicans commensalism is not the
      result of a benign behavior of one of the many components of human microbiota,
      but rather the result of host's potent innate and adaptive immune responses that
      restrict the growth of a potentially dangerous microrganism on the epithelia. An
      important asset guarding against the fungus is the Th17 functional subset of T
      helper cells. The selective loss of these cells with the progression of HIV
      infection causes the decay of fungal containment on the oral epithelium and
      allows C. albicans to express its pathogenic potential. An important part of this
      potential is represented by mechanisms to evade host immunity and enhance
      inflammation and immunoactivation. In C. albicans, these mechanisms are mostly
      incorporated into and expressed by characteristic morphogenic transitions such as
      the yeast-to-hyphal growth and the white-to-opaque switch. In addition, HIV
      infection generates an 'environment' selecting for overexpression of the
      virulence potential by the fungus, particularly concerning the secreted aspartyl
      proteinases (Saps). These enzymes can degrade critical host defense components
      such as complement and epithelial defensive proteins such as histatin-5 and E
      cadherin. It appears that part of this enhanced Candida virulence could be
      induced by the binding of the fungus to HIV and/or induced by HIV proteins such
      as GP160 and tat. Both OPC and OEC can be controlled by old and new antimycotics,
      but in the absence of host collaboration, anticandidal therapy may become
      ineffective in the long run. For these reasons, new therapeutics targeting
      virulence factors and specific immune interventions are being addressed. Among
      these new approaches, vaccination is a promising one. Two subunit vaccines based
      on antigens dominantly expressed by C. albicans in vivo, that is the Als3 adhesin
      and Sap2, have recently undergone phase 1 clinical trials. Overall, studies of
      Candida and candidiasis in the HIV-positive patient while certainly contributing
      to a more effective control of the microorganism may also provide useful
      information on HIV-host relationship itself that can assist the fight against the
      virus.

PMID- 22472854
TI  - An overview of intracellular interactions between immunodeficiency viruses and
      their hosts.
AB  - Many studies have documented how extensively HIV-1 and related viruses interact
      with host cells. Virus-host interactions are of two conceptual types. First,
      viruses have evolved to make use of numerous host-cell functions to facilitate
      their own replication. Second, hosts have evolved a number of activities to
      inhibit virus replication. Understanding the scope and details of HIV-host
      interactions has been an extraordinary rich scientific endeavor, and in addition
      to their biomedical importance, studies in this area have established HIV as a
      model system in virology. Here, I present an overview of how HIV-1 interacts with
      some key host cell factors during its replication cycle.

PMID- 22472855
TI  - Innate immunity in the control of HIV/AIDS:  recent advances and open questions.
AB  - From the publication of the first AIDS issue onwards, major advances have been
      made in the field of innate immunity during HIV infection. Innate immunity can be
      defined as the first and unspecific lines of defense constitutively present and
      ready to be mobilized upon infection. Although a large body of literature
      adamantly highlights that innate immunity is a critical weapon of defense against
      HIV and its simian parents (simian immunodeficiency virus, SIV), innate immunity
      is still underexplored. Focusing on innate immunity may open new paths for the
      development of innovative therapeutics and vaccine strategies against HIV.
      Understanding innate immunity may shed light on the natural protection occurring
      in rare HIV-1-infected individuals who control their infection. This review
      focuses on innate mechanisms sensing HIV-1 entry and controlling HIV-1 infection,
      as well as promoting inflammation and shaping adaptive immunity.

PMID- 22472856
TI  - Impact of malnutrition and social determinants on survival of HIV-infected adults
      starting antiretroviral therapy in resource-limited settings.
AB  - OBJECTIVES: Determining the impact of malnutrition, anaemia and social
      determinants on survival once starting antiretroviral therapy (ART) in a cohort
      of HIV-infected adults in a rural HIV care centre in Sihanoukville, Cambodia.
      METHODS: Retrospective and descriptive cohort study of adults starting ART
      between December 2004 and July 2009. We used the Kaplan-Meier and Cox regression
      survival analyses to identify predictors of death. RESULTS: Out of 1002 patients,
      49.7% were men; median age was 40; median time of follow-up was 2.4 years and
      10.4% died during the follow-up. At baseline, median CD4 cell count was 83
      cells/MUl, 79.9% were at WHO stage III or IV. In multivariate analysis,
      malnutrition appeared to be a strong and independent risk factor of death; 11.2%
      had a BMI less than 16 kg/m and hazard ratio was 6.97 [95% confidence interval
      (CI), 3.51-13.89], 21.5% had a BMI between 16 and 18 kg/m and hazard ratio was
      2.88 (95% CI, 1.42-5.82), 30.8% had a BMI between 18 and 20 kg/m and hazard ratio
      was 2.18 (95% CI, 1.09-4.36). Severe anaemia (haemoglobin<=8.4 g/dl) and CD4 cell
      count below 100 cells/MUl also predicted mortality, hazard ratio were 2.25 (95%
      CI, 1.02-4.34) and 2.29 (95% CI, 1.01-2.97), respectively. Social determinants
      were not significantly associated with death in univariate analysis. CONCLUSION:
      Malnutrition and anaemia are strong and independent prognostic factors at the
      time of starting ART. Nutritional cares are essential for the clinical success of
      HIV programs started in developing countries.

PMID- 22472857
TI  - Mortality due to cancer among people with AIDS:  a novel approach using registry
      linkage data and population attributable risk methods.
AB  - OBJECTIVE: Deaths related to HIV/AIDS have declined due to improved HIV
      therapies. However, people with AIDS remain at elevated risk for cancer and
      cancer deaths. Prior studies evaluated cancer deaths using death certificates,
      which may be inaccurate. We utilized population attributable risk methods (which
      do not rely on death certificates) to assess cancer mortality. DESIGN: Data from
      a US population-based record linkage study were used to identify incident cancers
      and deaths in 372 364 people with AIDS (1980-2006) followed for up to 5 years
      after AIDS onset. We utilized Cox regression to compare mortality in individuals
      with and without cancer and to calculate cancer-attributable mortality across
      calendar periods (AIDS onset in 1980-1989, 1990-1995, and 1996-2006). RESULTS:
      Mortality declined across calendar periods for all people with AIDS but remained
      higher among those with cancer relative to those without. During 1996-2006, among
      individuals with an AIDS-defining cancer (ADC) who died, 88.3% of deaths were
      attributable to their ADC; likewise, among individuals with a non-AIDS-defining
      cancer (NADC), 87.1% of deaths were attributable to their NADC. The fraction of
      all deaths in people with AIDS attributable to ADC (i.e. population-attributable
      risk) decreased significantly from 6.3% (1980-1990) to 3.9% (1996-2006), but NADC
      population attributable mortality increased significantly over time from 0.5%
      (1980-1989) to 2.3% (1996-2006). CONCLUSION: Among individuals with AIDS and
      cancer who subsequently die, most deaths are attributable to cancer. With a
      decline in overall mortality, the proportion of all deaths attributable to NADCs
      has increased. These results highlight the need for improved cancer prevention
      and treatment.

PMID- 22472858
TI  - HIV reservoirs:  pathogenesis and obstacles to viral eradication and cure.
AB  - Plasma HIV viremia can be suppressed and maintained below the limits of detection
      for prolonged periods of time in the vast majority of HIV-infected individuals
      who receive antiretroviral therapy (ART). Thus, the clinical outcome for HIV
      infected individuals who have access to these drugs is dramatically improved.
      However, ART alone cannot eradicate HIV in infected individuals and this
      impediment is likely in part due to the persistence of viral reservoirs in the
      peripheral blood and lymphoid tissues of infected individuals despite the
      suppression of plasma viremia. In recent years, major research efforts have been
      dedicated to a better understanding of the pathogenesis of persistent HIV
      infection and to the development of therapeutic strategies aimed at eradicating
      virus in infected individuals receiving ART. In this review, we discuss the
      pathophysiology of CD4 T-cell HIV reservoirs, including recent advances in our
      understanding of the mechanisms of persistent viral infection and perspectives
      for eradication of HIV in infected individuals.

PMID- 22472859
TI  - The potential role of prostaglandin D2 in nasal congestion observed in a guinea
      pig model of allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is the most common allergic disease, displaying the
      typical nasal symptom of congestion. Prostaglandin D(2) (PGD(2)), a chemical
      mediator released in large amounts by mast cells upon allergic stimulation in
      humans, is known to be involved in nasal congestion. However, the mechanism by
      which this congestion occurs remains unclear. METHODS: The effect of PGD(2) on
      the nasal airflow in guinea pigs was measured using a noninvasive approach that
      avoided any anesthetic effect. Isometric tension of isolated nasal mucosa and the
      nasal vascular corrosion resin cast technique were used to clarify the area of
      nasal mucosal vessels affected by PGD(2), and to examine the mechanism of PGD(2)
      induced nasal congestion. Moreover, the involvement of second messengers in
      PGD(2)-induced mucosal relaxation was investigated. RESULTS: PGD(2) induced an
      increase in intranasal pressure in a guinea pig model of rhinitis. Additionally,
      sinusoidal microvessel dilatation appeared around the septum using the vascular
      corrosion resin cast technique in the nasal mucosa. Moreover, relaxation of the
      nasal mucosa following stimulation of the prostanoid DP-1 receptor was associated
      with cAMP levels in the tissue. CONCLUSIONS: PGD(2)-induced nasal congestion is
      caused by direct dilatation of the sinusoid vessels through the increase of cAMP
      levels in the nasal mucosa, demonstrating that the mechanism of PGD(2)-induced
      nasal congestion is different from other chemical mediators. Consequently,
      antagonists for the prostanoid DP-1 receptor would be an alternative approach for
      the relief of nasal congestion. Alternatively, the combined administration with
      antagonists for other mediators involved in nasal congestion may also be a
      valuable therapy for allergic rhinitis.

PMID- 22472860
TI  - Lucinactant approved for respiratory distress syndrome.

PMID- 22472861
TI  - Data silos impede progress against prescription drug abuse.

PMID- 22472862
TI  - Pharmacists see positives in nontraditional residency programs.

PMID- 22472863
TI  - Criminal charges not necessarily criminalization of medication error.

PMID- 22472864
TI  - Pharmacist involvement in medical missions: planning, execution, and assessment.

PMID- 22472865
TI  - Tips for the first trainee in a new pharmacy residency program.

PMID- 22472866
TI  - Ecallantide for treatment of acute attacks of hereditary angioedema.
AB  - PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, dosage,
      administration, adverse effects, and place in therapy of ecallantide, a
      kallikrein inhibitor for the treatment of hereditary angioedema (HAE), are
      reviewed. SUMMARY: Ecallantide is the first member of the kallikrein inhibitor
      class approved for the treatment of acute attacks of HAE. Ecallantide works by
      binding to kallikrein, preventing the conversion of kininogen to bradykinin,
      which reduces vascular permeability, thus reducing the swelling associated with
      acute attacks of HAE. Ecallantide has been studied for the treatment of HAE in
      three Phase II studies and two Phase III studies. These studies were collectively
      known as the EDEMA (Evaluation of DX-88's Effect in Mitigating Angioedema)
      studies. Phase III clinical trials found that ecallantide is superior to placebo
      in ameliorating patient symptoms associated with acute attacks of HAE at any
      anatomical site. Ecallantide has a favorable safety profile, with the most common
      adverse effects being gastrointestinal effects, headache, and injection site
      reactions. The most severe adverse effects of ecallantide are the risk of
      anaphylaxis and the possible development of antiecallantide antibodies. A risk
      evaluation and mitigation strategy program has been approved by the Food and Drug
      Administration to help ensure the safety and efficacy of ecallantide use. The
      recommended dose is 30 mg given as three separate subcutaneous injections.
      CONCLUSION: Ecallantide is a novel agent approved for the treatment of acute
      attacks of HAE at any anatomical site. It is one of only three medications
      approved for this indication in the United States, presents a unique mechanism of
      action, and appears to be safe and effective when used for its labeled
      indication.

PMID- 22472867
TI  - Pharmacologic prophylaxis against venous thromboembolism in hospitalized patients
      with cirrhosis and associated coagulopathies.
AB  - PURPOSE: Published evidence on the incidence and predictors of venous
      thromboembolism (VTE) in patients with cirrhosis of the liver is reviewed.
      SUMMARY: The frequently observed phenomenon of elevated International Normalized
      Ratio (INR) values in patients with cirrhosis has led to a theory of
      "autoanticoagulation" and the assertion that such patients may not benefit from
      the VTE risk-reduction therapies routinely used in other groups of hospitalized
      patients. A literature search identified six reports specifically addressing the
      issue of VTE risk in patients with cirrhosis. Reported rates of VTE development
      in such patients vary widely (0.5-8.2%) as a result of investigators' use of
      varying study methods and endpoints. The results of three studies (including two
      studies of longitudinal data on about 100,000 and nearly 450,000 patients) found
      no significant correlation of INR values and VTE risk. With regard to potential
      clinical markers of VTE risk in the context of cirrhosis, data from two studies
      suggested that serum albumin might serve as a reliable marker of coagulation
      status and, therefore, VTE risk. The results of other studies indicated that
      independent predictors of VTE in patients with cirrhosis include malnutrition and
      significant comorbidities such as chronic kidney disease and congestive heart
      failure. In aggregate, the available evidence does not support the
      autoanticoagulation theory. CONCLUSION: In hospitalized patients with cirrhosis
      who have elevated INR values, pharmacologic VTE prophylaxis should be strongly
      considered if there is no active or recent bleeding and if more than one risk
      factor for VTE is present.

PMID- 22472870
TI  - ASHP professional policy recommendations--invitation to comment.

PMID- 22472868
TI  - Implementation of a hypertension clinic using a streamlined treatment algorithm.
AB  - PURPOSE: The implementation of a pharmacist-managed clinic based on the
      Simplified Treatment Intervention to Control Hypertension (STITCH) algorithm is
      described, with insights on physician acceptance and implementation challenges.
      SUMMARY: After a medical records review indicating gaps in the follow-up care of
      emergency department (ED) patients found to have elevated blood pressures (BPs),
      the ED of a large public hospital sought to create a "bridge" to ongoing primary
      care by applying a modified version of the STITCH algorithm, which aims to
      address compliance barriers to adequate BP control through a streamlined stepped
      care approach derived from national consensus guidelines. Following the
      guidelines of the STITCH algorithm, the goals of the clinic implemented in this
      project were to (1) coordinate initial pharmacotherapy, (2) monitor patients
      pending their first primary care clinic appointment, (3) assess for potential
      antihypertensive-related complications, and (4) provide comprehensive and ongoing
      patient education. Physician support for the clinic (staffed by one pharmacist
      one day weekly) was cultivated through both broad and individually targeted
      education to allay concerns about initiating BP-lowering therapy in the ED
      setting, especially given patients' typical one- to six-month wait time for a
      primary care clinic appointment. Early experience at the clinic indicated
      increased physician willingness to initiate hypertension treatment in the ED due
      to the availability of appropriate follow-up services within a shorter time frame
      (about two weeks). CONCLUSION: One hospital's experience suggests that a
      hypertension-focused clinic using a streamlined treatment algorithm can serve as
      a bridge from urgent care to ongoing primary care, facilitating adequate BP
      control in a transient, low-income patient population.

PMID- 22472871
TI  - Prognostic value of synaptophysin and chromogranin a expression in patients
      receiving palliative chemotherapy for advanced non-small-cell lung cancer.
AB  - BACKGROUND: Chemotherapy is the principal treatment method for patients with
      advanced non-small-cell lung cancer (NSCLC). Treatment with platinum-based and
      novel chemotherapeutic regimens, compared to monotherapy, slightly increases the
      response rates to 20-40%. The predictive and prognostic values of molecular
      factors are highly variable; however, data on clinical-demographic factors are
      still burdened by significant limitations. OBJECTIVES: The aim of this study was
      to assess the prognostic value of synaptophysin and chromogranin A protein
      expression in patients receiving palliative chemotherapy for advanced NSCLC.
      METHODS: The study population consisted of 23 women and 116 men. The median age
      was 57.3 years. Expression of synaptophysin and chromogranin was assessed using a
      two-step model of immunohistochemical staining. Level 0 represented lack of
      activity, while level 1 represented its expression. RESULTS: Expression of
      synaptophysin and chromogranin A was observed in 12 (8.6%) and 5 (3.6%) patients,
      respectively. The risk of death was significantly lower in patients with
      expression of synaptophysin (p = 0.008) and chromogranin A (p = 0.014). The 12-
      and 24-month survival rate of patients with synaptophysin expression was 64% (95%
      CI 0.35-0.93), while for patients without expression it was 46% (95% CI 0.36
      0.56) and 16% (95% CI 0.07-0.25), respectively. The 12- and 24-month survival
      rate of patients with chromogranin expression was 80% (95% CI 0.44-1.00), while
      for chromogranin A-negative patients it was 47% (95% CI 0.37-0.57) and 19% (95%
      CI 0.10-0.28), respectively. We did not observe associations between expression
      of synaptophysin and chromogranin A and the other typical prognostic factors.
      CONCLUSIONS: Expression of synaptophysin and chromogranin A was associated with a
      longer median overall survival and might have prognostic value. These results
      should be confirmed in a prospective study.

PMID- 22472872
TI  - Dopaminergic modulation of CD4+CD25(high) regulatory T lymphocytes in multiple
      sclerosis patients during interferon-beta therapy.
AB  - OBJECTIVE: We investigated dopaminergic inhibition of CD4+CD25(high) regulatory T
      lymphocytes (Treg) in relapsing-remitting multiple sclerosis (MS) patients
      treated with interferon (IFN)-beta. METHODS: MS patients were prospectively
      studied at baseline and during 1 year of IFN-beta, and compared with healthy
      controls (HCs). Treg were separated by immunomagnetic sorting and the effect of
      dopamine (DA) on Treg was assessed in coculture experiments with homologous
      effector T lymphocytes (Teff). Tyrosine hydroxylase (TH), dopaminergic receptors
      (DR) D3 and D5, and forkhead box protein P3 (FoxP3) mRNA were assessed by real
      time PCR. Circulating CD4+ T cell subsets were assessed by flow cytometry.
      RESULTS: In coculture experiments, Treg inhibition of Teff proliferation was
      reduced by DA in HCs and completely abolished in MS patients at baseline.
      However, in patients after 12 months of IFN-beta, Teff proliferation was impaired
      and DA had no more effect on Treg. In comparison to cells from HCs, Treg from MS
      patients at baseline had increased mRNA for DR D5 and TH (but not for DR D3).
      During treatment with IFN-beta, both DR D5 and TH mRNA decreased down to values
      lower than those of cells from HCs. In comparison to HCs, MS patients had a
      higher frequency of circulating Treg, both at baseline and after IFN-beta, while
      FoxP3 mRNA levels in Treg were similar in patients and HCs and did not show major
      changes during IFN-beta. CONCLUSIONS: Dopaminergic inhibition of Treg in MS
      patients is suppressed during IFN-beta treatment. Treg play a key role in the
      suppression of autoimmunity, thus the effect may have a therapeutic repercussion.

PMID- 22472873
TI  - High frequency of potentially pathogenic SORL1 mutations in autosomal dominant
      early-onset Alzheimer disease.
AB  - Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer
      disease (ADEOAD) index cases without mutation on known genes (amyloid precursor
      protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in
      five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4)
      mutations. These mutations were not retrieved in 1500 controls of same ethnic
      origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non
      synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a
      total of 7/29 unknown mutations in the combined sample. Using in silico
      predictions, we conclude that these seven private mutations are likely to have a
      pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a
      protein involved in the control of amyloid beta peptide production. Our results
      suggest that besides the involvement of the APP and PSEN genes, further genetic
      heterogeneity, involving another gene of the same pathway is present in ADEOAD.

PMID- 22472874
TI  - Modeling psychiatric disorders at the cellular and network levels.
AB  - Although psychiatric disorders such as autism spectrum disorders, schizophrenia
      and bipolar disorder affect a number of brain regions and produce a complex array
      of clinical symptoms, basic phenotypes likely exist at the level of single
      neurons and simple networks. Being highly heritable, it is hypothesized that
      these disorders are amenable to cell-based studies in vitro. Using induced
      pluripotent stem cell-derived neurons and/or induced neurons from fibroblasts,
      limitless numbers of live human neurons can now be generated from patients with a
      genetic background permissive to the disease state. We predict that cell-based
      studies will ultimately contribute to our understanding of the initiation,
      progression and treatment of these psychiatric disorders.

PMID- 22472875
TI  - Deep resequencing and association analysis of schizophrenia candidate genes.

PMID- 22472878
TI  - Biomimetic catalytic enantioselective decarboxylative aldol reaction of beta
      ketoacids with trifluoromethyl ketones.
AB  - We disclose an organocatalyzed enantioselective decarboxylative ketone aldol
      reaction of beta-ketoacids with trifluoromethyl ketones in the presence of
      biscinchona alkaloid (DHQD)(2)AQN, affording chiral tertiary alcohols in up to
      98% yield and 90% ee.

PMID- 22472877
TI  - Is bipolar disorder more common in highly intelligent people? A cohort study of a
      million men.
AB  - Anecdotal and biographical reports have long suggested that bipolar disorder is
      more common in people with exceptional cognitive or creative ability.
      Epidemiological evidence for such a link is sparse. We investigated the
      relationship between intelligence and subsequent risk of hospitalisation for
      bipolar disorder in a prospective cohort study of 1,049,607 Swedish men.
      Intelligence was measured on conscription for military service at a mean age of
      18.3 years and data on psychiatric hospital admissions over a mean follow-up
      period of 22.6 years was obtained from national records. Risk of hospitalisation
      with any form of bipolar disorder fell in a stepwise manner as intelligence
      increased (P for linear trend <0.0001). However, when we restricted analyses to
      men with no psychiatric comorbidity, there was a 'reversed-J' shaped association:
      men with the lowest intelligence had the greatest risk of being admitted with
      pure bipolar disorder, but risk was also elevated among men with the highest
      intelligence (P for quadratic trend=0.03), primarily in those with the highest
      verbal (P for quadratic trend=0.009) or technical ability (P for quadratic trend
      <0.0001). At least in men, high intelligence may indeed be a risk factor for
      bipolar disorder, but only in the minority of cases who have the disorder in a
      pure form with no psychiatric comorbidity.

PMID- 22472879
TI  - Dynamic equilibrium between cancer stem cells and non-stem cancer cells in human
      SW620 and MCF-7 cancer cell populations.
AB  - BACKGROUND: Cancer stem cells (CSCs) paradigm suggests that CSCs might have
      important clinical implications in cancer therapy. Previously, we reported that
      accumulation efficiency of CSCs is different post low- and high-LET irradiation
      in 48 h. METHODS: Cancer stem cells and non-stem cancer cells (NSCCs) were sorted
      and functionally identified through a variety of assays such as antigen profiles
      and sphere formation. Inter-conversion between CSCs and NSCCs were in situ
      visualised. Cancer stem cells proportions were assayed over multiple generations
      under normal and irradiation surroundings. Supplement and inhibition of TGF
      beta1, as well as immunofluorescence assay of E-cadherin and Vimentin, were
      performed. RESULTS: Surface antigen markers of CSCs and NSCCs exist in an
      intrinsic homoeostasis state with spontaneous and in situ visualisable inter
      conversions, irrespective of prior radiations. Supplement with TGF-beta1
      accelerates the equilibrium, whereas inhibition of TGF-beta signalling disturbs
      the equilibrium and significantly decreases CSC proportion. Epithelial
      mesenchymal transition (EMT) might be activated during the process. CONCLUSION:
      Our results indicate that the intrinsic inter-conversion and dynamic equilibrium
      between CSCs and NSCCs exist under normal and irradiation surroundings, and TGF
      beta might have important roles in the equilibrium through activating EMT.

PMID- 22472880
TI  - MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of
      colorectal cancer patients.
AB  - BACKGROUND: Upregulation of the matrix metalloproteinases MMP-2 and MMP-9 in
      various cancers has been associated with worse survival of the patients. METHODS:
      We assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal
      cancer patients in relation to the course of the disease. RESULTS: A high protein
      expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated
      with worse 5-year survival. The combination of both parameters was an even
      stronger prognostic factor. These protein levels were found not to be related to
      the corresponding single nucleotide polymorphisms of MMP-2 (-1306C>T) and MMP-9 (
      1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in
      normal mucosa are prognostic for survival, independent of TNM classification.
      CONCLUSION: MMP-2 and MMP-9 levels in normal mucosa are indicative of the course
      of disease in colorectal cancer patients.

PMID- 22472876
TI  - A mega-analysis of genome-wide association studies for major depressive disorder.
AB  - Prior genome-wide association studies (GWAS) of major depressive disorder (MDD)
      have met with limited success. We sought to increase statistical power to detect
      disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery
      phase, we analyzed more than 1.2 million autosomal and X chromosome single
      nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of
      recent European ancestry (9240 MDD cases and 9519 controls). In the MDD
      replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases
      and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819
      autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium
      bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP
      cases/7775 controls). No SNPs achieved genome-wide significance in the MDD
      discovery phase, the MDD replication phase or in pre-planned secondary analyses
      (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal
      onset MDD or typical-like MDD from a latent class analyses of the MDD criteria).
      In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide
      significance (P<5 * 10(-8)), and all were in a 248 kb interval of high LD on
      3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 * 10(-9) at rs2535629).
      Although this is the largest genome-wide analysis of MDD yet conducted, its high
      prevalence means that the sample is still underpowered to detect genetic effects
      typical for complex traits. Therefore, we were unable to identify robust and
      replicable findings. We discuss what this means for genetic research for MDD. The
      3p21.1 MDD-BIP finding should be interpreted with caution as the most significant
      SNP did not replicate in MDD samples, and genotyping in independent samples will
      be needed to resolve its status.

PMID- 22472881
TI  - Mitochondrial D310 mutations in the early development of breast cancer.
AB  - BACKGROUND: The role of mitochondrial DNA (mtDNA) mutations in the development of
      breast cancer is largely unknown. In this study, we investigated the frequency
      and pattern of mutations in the D310 region, the most commonly mutated region in
      mtDNA, in a series of breast lesions. METHODS: Using capillary electrophoresis,
      we genotyped the D310 sequence of neoplastic epithelial cells from 23 patients
      with synchronous ductal carcinoma in situ (DCIS) and invasive ductal carcinoma
      (IDC), 26 patients with IDC only and 29 patients with DCIS only. RESULTS: A
      majority of DCIS (68.4%) and IDC (71.4%) lesions harbour different D310 sequences
      compared with their matched normal control. Specific D310 sequences were more
      frequently identified in tumour samples (77.1% of DCIS and 75.5% of IDC) compared
      with normal tissues (35.3% of normal; P<0.0001). No difference was identified
      between DCIS lesions with synchronous IDC and those from pure DCIS cases. In five
      cases, histologically normal tissue adjacent to tumour was found to share D310
      sequences with the tumour, while normal tissue taken further away did not.
      CONCLUSION: Although D310 alterations do not seem to be related to DCIS
      progression, they were found in histologically normal cells adjacent to tumour.
      This suggests a field of genetically altered cells, thus D310 mutations could
      represent a potential marker for the clonal expansion of premalignant breast
      cancer cells.

PMID- 22472882
TI  - PPARgamma inhibits hepatocellular carcinoma metastases in vitro and in mice.
AB  - BACKGROUND: We have previously demonstrated that peroxisome proliferator
      activated receptor (PPARgamma) activation inhibits hepatocarcinogenesis. We aim
      to investigate the effect of PPARgamma on hepatocellular carcinoma (HCC)
      metastatic potential and explore its underlying mechanisms. METHODS: Human HCC
      cells (MHCC97L, BEL-7404) were infected with adenovirus-expressing PPARgamma (Ad
      PPARgamma) or Ad-lacZ and treated with or without PPARgamma agonist
      (rosiglitazone). The effects of PPARgamma on cell migration and invasive activity
      were determined by wound healing assay and Matrigel invasive model in vitro, and
      in an orthotopic liver tumour metastatic model in mice. RESULTS: Pronounced
      expression of PPARgamma was demonstrated in HCC cells (MHCC97L, BEL-7404) treated
      with Ad-PPARgamma, rosiglitazone or Ad-PPARgamma plus rosiglitazone, compared
      with control (Ad-LacZ). Such induction markedly suppressed HCC cell migration.
      Moreover, the invasiveness of MHCC97L and BEL-7404 cells infected with Ad
      PPARgamma, or treated with rosiglitazone was significantly diminished up to 60%.
      Combination of Ad-PPARgamma and rosiglitazone showed an additive effect.
      Activation of PPARgamma by rosiglitazone significantly reduced the incidence and
      severity of lung metastasis in an orthotopic HCC mouse model. Key mechanisms
      underlying the effect of PPARgamma in HCC include upregulation of cell adhesion
      genes, E-cadherin and SYK (spleen tyrosine kinase), extracellular matrix
      regulator tissue inhibitors of metalloproteinase (TIMP) 3, tumour suppressor gene
      retinoblastoma 1, and downregulation of pro-metastatic genes MMP9 (matrix
      metallopeptidase 9), MMP13, HPSE (heparanase), and Hepatocyte growth factor
      (HGF). Direct transcriptional regulation of TIMP3, MMP9, MMP13, and HPSE by
      PPARgamma was shown by ChIP-PCR. CONCLUSION: Peroxisome proliferator-activated
      receptor-gamma exerts an inhibitory effect on the invasive and metastatic
      potential of HCC in vitro and in vivo, and is thus, a target for the prevention
      and treatment of HCC metastases.

PMID- 22472883
TI  - Evidence for under-diagnosis of childhood acute lymphoblastic leukaemia in poorer
      communities within Great Britain.
AB  - BACKGROUND: Recorded incidence of childhood acute lymphoblastic leukaemia tends
      to be lower in poorer communities. A 'preemptive infection hypothesis' proposes
      that some children with leukaemia die from infection without diagnosis of
      leukaemia. Various different blood abnormalities can occur in untreated
      leukaemia. METHODS: Logistic regression was used to compare pre-treatment blood
      counts among children aged 1-13 years at recruitment to national clinical trials
      for acute lymphoblastic leukaemia during 1980-2002 (N=5601), grouped by address
      at diagnosis within Great Britain into quintiles of the 1991 Carstairs
      deprivation index. Children combining severe neutropenia (risk of serious
      infection) with relatively normal haemoglobin and platelet counts (lack of pallor
      and bleeding) were postulated to be at risk of dying from infection without
      leukaemia being suspected. A deficit of these children among diagnosed patients
      from poorer communities was predicted. RESULTS: As predicted, there was a deficit
      of children at risk of non-diagnosis (two-sided P(trend)=0.004; N=2009), and an
      excess of children with pallor (P(trend)=0.045; N=5535) and bleeding
      (P(trend)=0.036; N=5541), among cases from poorer communities. CONCLUSION: Under
      diagnosis in poorer communities may have contributed to socioeconomic variation
      in recorded childhood acute lymphoblastic leukaemia incidence within Great
      Britain, and elsewhere. Implications for clinical practice and epidemiological
      studies should be considered.

PMID- 22472884
TI  - Negative argininosuccinate synthetase expression in melanoma tumours may predict
      clinical benefit from arginine-depleting therapy with pegylated arginine
      deiminase.
AB  - BACKGROUND: Arginine-depleting therapy with pegylated arginine deiminase (ADI
      PEG20) was reported to have activity in advanced melanoma in early phase I-II
      trial, and clinical trials are currently underway in other cancers. However, the
      optimal patient population who benefit from this treatment is unknown. METHODS:
      Advanced melanoma patients with accessible tumours had biopsy performed before
      the start of treatment with ADI-PEG20 and at the time of progression or relapse
      when amenable to determine whether argininosuccinate synthetase (ASS) expression
      in tumour was predictive of response to ADI-PEG20. RESULTS: Twenty-seven of
      thirty-eight patients treated had melanoma tumours assessable for ASS staining
      before treatment. Clinical benefit rate (CBR) and longer time to progression were
      associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS
      positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial
      response and 5 had stable disease, when ASS expression was negative (ASS-),
      giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative
      ASS expression before therapy had rebiopsy after tumour progression and the ASS
      expression became positive. The survival of ASS- patients receiving at least four
      doses at 320 IU m(-2) was significantly better than the ASS+ group at 26.5 vs 8.5
      months, P=0.024. CONCLUSION: ADI-PEG20 is safe and the drug is only efficacious
      in melanoma patients whose tumour has negative ASS expression. Argininosuccinate
      synthetase tumour positivity is associated with drug resistance and tumour
      progression.

PMID- 22472885
TI  - Personalised cancer follow-up: risk stratification, needs assessment or both?

PMID- 22472886
TI  - The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging
      between HPV-related head and neck cancer and cervical cancer.
AB  - BACKGROUND: Although the role of human papilloma virus (HPV) in cervical squamous
      cell carcinoma (CSCC) is well established, the role in head and neck SCC (HNSCC)
      is less clear. MicroRNAs (miRNAs) have a role in the cancer development, and HPV
      status may affect the miRNA expression pattern in HNSCC. To explore the influence
      of HPV in HNSCC, we made a comparative miRNA profile of HPV-positive (HPV+) and
      HPV-negative (HPV-) HNSCC against CSCC. METHODS: Fresh frozen and laser
      microdissected-paraffin-embedded samples obtained from patients with HPV+/HPV-
      HNSCC, CSCC and controls were used for microarray analysis. Differentially
      expressed miRNAs in the HPV+ and HPV- HNSCC samples were compared with the
      differentially expressed miRNAs in the CSCC samples. RESULTS: Human papilloma
      virus positive (+) HNSCC had a distinct miRNA profile compared with HPV- HNSCC.
      Significantly more similarity was seen between HPV+ HNSCC and CSCC than HPV- and
      CSCC. A set of HPV core miRNAs were identified. Of these especially the miR
      15a/miR-16/miR195/miR-497 family, miR-143/miR-145 and the miR-106-363 cluster
      appear to be important within the known HPV pathogenesis. CONCLUSION: This study
      adds new knowledge to the known pathogenic pathways of HPV and substantiates the
      oncogenic role of HPV in subsets of HNSCCs.

PMID- 22472887
TI  - Cadmium influences  the 5-Fluorouracil cytotoxic effects on breast cancer cells.
AB  - The aim of the research was to evaluate a heavy metal, Cadmium (Cd), which was
      used to produce alterations in human breast cancer cell line MCF-7. Moreover, we
      analyzed both immunohistochemical and ultrastructural alterations induced by the
      antineoplastic drug, 5-Fluorouracil (5-FU), after exposure to different
      concentrations of Cadmium. Also, we compared the effects of these compounds on
      actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation,
      control cells looked polymorphous with filopodia. In cells already treated with
      small concentrations of Cd, after brief times of incubation, we observed an
      intense metabolic activity with larger, clearer, and elongated mitochondria
      characterized by thin and numerous dilated cristae. 5-FU-treated cells showed
      cytotoxicity signs with presence of pore-like alterations in the cell membrane
      and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5
      MUM) to the cells treated with Cd (5 MUM-20 MUM) did not induce significant
      ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU
      treated cells mitochondria with globular aspect and regular cristae indicated the
      active metabolic state. In cells treated only with Cd we observed alterations in
      actin distribution, while tubulin branched out throughout the cytoplasm. With the
      association of Cd+5FU, we observed less morphological alterations in both tubulin
      and actin cytoskeleton proteins. Although the mechanism remains unknown at
      present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on
      breast cancer cells. These preliminary results could have an important clinical
      application in patients with breast cancer.

PMID- 22472888
TI  - Dynamics of calcitonin gene-related peptide-like cells changes in the lungs of
      two-kidney, one-clip rats.
AB  - Taking into consideration renal hypertension-induced homeostatic disorders and
      the key role of calcitonin gene-related peptide (CGRP) in many, systemic
      functions regulating systems, a question arises as to what an extent arterial
      hypertension affects the morphology and dynamics of pulmonary CGRP-immunopositive
      cell changes. The aim of the present study was to examine the distribution,
      morphology and dynamics of changes of CGRP-containing cells in the lungs of rats
      in the two-kidney, one-clip (2K1C) renovascular hypertension model. The studies
      were carried out on the lungs of rats after 3, 14, 28, 42, and 91 days long
      period from the renal artery clipping procedure. In order to identify
      neuroendocrine cells, immunohistochemical reaction was performed with the use of
      a specific antibody against CGRP. It was revealed that renovascular hypertension
      caused changes in the neuroendocrine, CGRP-containing cells in the lungs of rats.
      The changes, observed in the neuroendocrine cells, depended on time periods from
      experimentally induced hypertension. The highest intensity of changes in the
      neuroendocrine cells was observed in the lungs of rats after 14 days from the
      surgery.

PMID- 22472889
TI  - Histochemistry for studying structure and function of the articular disc of the
      human temporomandibular joint.
AB  - The articular disc of the temporomandibular joint (TMJ) is composed of
      fibrocartilage, and the extracellular matrix of this disc is composed mainly of
      collagen, glycosaminoglycan and proteoglycans. Research on the changes that occur
      in the composition of the articular disc of the TMJ is necessary for
      understanding the basis of the pathological process of internal derangement (ID),
      and a number of reports have been published in recent years on the application of
      refined histochemical techniques to investigate the structure and function of the
      TMJ.  The direction of future TMJ disc studies should be towards obtaining more
      evidence to support previous results, and should hopefully be of practical use in
      terms of prevention and cure of ID.

PMID- 22472890
TI  - pPKCalpha mediated-HIF-1alpha activation related to the morphological
      modifications occurring in neonatal myocardial tissue in response to severe and
      mild hyperoxia.
AB  - In premature babies birth an high oxygen level exposure can occur and newborn 
      hyperoxia exposure can be associated with free radical oxygen release with
      impairment of myocardial function, while in adult animal models short exposure to
      hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms
      and consequences which take place after hyperoxia exposure are different and
      related to animals age.  The aim of our work  has been to analyze the role played
      by HIF-1alpha in the occurrence of the morphological modifications upon hyperoxia
      exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment
      increase which seems to allow enhanced blood vessels growth. An increased hypoxia
      inducible factor-1alpha (HIF-1alpha) translocation and vascular endothelial
      growth factor (VEGF) expression has been found upon 95% oxygen exposure to induce
      morphological modifications. Upstream pPKC-alpha expression increase in newborn
      rats exposed to 95% oxygen can suggest PKC involvement in HIF-1alpha activation.
      Since nitric oxide synthase (NOS)  are involved in heart vascular regulation,
      endothelial NOS (e-NOS) and inducible NOS (i-NOS) expression has been
      investigated: a lower eNOS and an higher iNOS expression has been found in
      newborn rats exposed to 95% oxygen related to the evidence that hyperoxia
      provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action,
      respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax
      expression analyses, seems more evident in sample exposed to severe hyperoxia. 
      All in all such results suggest that in newborn rats hyperoxia can trigger oxygen
      free radical mediated membrane injury through a pPKCalpha mediated HIF-1alpha
      signalling system, even though specificity of such response could be obtained by
      in vivo administration to the rats of specific inhibitors of PKCalpha. This
      intracellular signalling can switch molecular events leading to blood vessels
      development in parallel to pro-apoptotic events due to an immature anti-oxidant
      defensive system in newborn rat hearts.

PMID- 22472891
TI  - Fluorescence properties of the Na+/H+exchanger inhibitor HMA (5-(N,N
      hexamethylene)amiloride) are modulated by intracellular pH.
AB  - HMA (5-(N,N-hexamethylene)amiloride), which belongs to a family of novel
      amiloride derivatives, is one of the most effective inhibitors of Na+/H+
      exchangers, while uneffective against Na+ channels and Na+/Ca2+ exchangers. In
      this study, we provided evidence that HMA can act as a fluorescent probe. In
      fact, human retinal ARPE19 cells incubated with HMA show an intense bluish
      fluorescence in the cytoplasm when observed at microscope under conventional UV
      excitation conditions. Interestingly, a prolonged observation under continuous
      exposure to excitation lightdoes not induce great changes in cells incubated with
      HMA for times up to about 5 min, while an unexpected rapid increase in
      fluorescence signal is observed in cells incubated for longer times. The latter
      phenomenon is particularly evident in the perinuclear region and in discrete
      spots in the cytoplasm. Since HMA modulates intracellular acidity, the dependence
      of its fluorescence properties on medium pH and response upon irradiation have
      been investigated in solution, at pH 5.0 and pH 7.2. The changes in both spectral
      shape and amplitude emission indicate a marked pH influence on HMA fluorescence
      properties, making HMA exploitable as a self biomarker of pH alterations in cell
      studies, in the absence of perturbations induced by the administration of other
      exogenous dyes.

PMID- 22472892
TI  - Intracellular distribution of Tankyrases as detected by multicolor
      immunofluorescence techniques.
AB  - Poly(ADP-ribose) polymerases are a family of enzymes that catalyze the conversion
      of NAD+ into ADP-ribose. Among them, Tankyrases have been found to bind to
      centrosome, mitotic spindle and microsome proteins, in the cytoplasm, and to
      telomeres in the nucleus, where they play a relevant role in telomere metabolism.
      However, their precise intracellular localization during interphase has not been
      so far fully elucidated. We investigated this aspect in situ by double
      immunofluorescence experiments using antibodies recognizing Tankyrases 1-2 or
      other proteins residing in specific organelles (Golgi apparatus, mitochondria,
      lysosomes, endoplasmic reticulum). We used HeLa cells as a model system in vitro,
      before and after treatment with either actinomycin D or etoposide, to also
      investigate the possible relocation of Tankyrases during apoptosis. We observed
      that Tankyrases are distributed both in the nucleus and in the cytoplasm; in this
      latter compartment, they were found to colocate with the Golgi apparatus but
      never with the mitochondria; a pool of Tankyrases also colocates with the
      endoplasmic reticulum and lysosomes. Interestingly, in cells with clear signs of
      apoptosis, Tankyrases were detectable in the cytoplasmic blebs: this suggests
      that they are not massively cleaved during apoptosis and persist in the largely
      heterogeneous apoptotic remnants which are known to contain components of
      cytoplasmic and nuclear origin.

PMID- 22472893
TI  - An immunohistochemical study of the pancreatic endocrine cells of the Korean
      golden frog, Rana plancyi chosenica.
AB  - The regional distribution and quantitative frequency of pancreatic endocrine
      cells were demonstrated in the Korean golden frog (Rana plancyi chosenica Okada),
      which is known as a Korean endemic species, for the first time, by
      immunohistochemical methods using specific mammalian antisera to insulin,
      glucagon, somatostatin and human pancreatic polypeptide (PP). In the pancreas of
      the Korean golden frog, all four endocrine cell types were demonstrated. Insulin-
      and glucagon-positive cells were located in the pancreas as single cells or islet
      like clusters with frequencies of 85.90+/-18.28 and 54.30+/-8.77/1,000/1,000
      cells, respectively. Somatostatin-containing cells were also dispersed in the
      pancreas as single cells or clusters but in the case of clusters, they are
      exclusively situated in the marginal regions of insulin- or glucagon-positive
      cell clusters. Cells stained for somatostatin cell frequency was 15.50+/
      3.10/1000 cells. PP-containing cells were also distributed as single cells or
      clusters with frequency of 53.40+/-11.96/1,000 cells. Clusters consisted of PP
      positive cells are distributed as a core type and a marginally distributed type.
      Overall, there were 40.84+/-3.81% insulin-, 26.02+/-1.71% glucagon-, 7.63+/-2.09%
      somatostatin- and 25.51+/-3.26% PP-IR cells.

PMID- 22472894
TI  - Histochemical localization of sialic acids and antimicrobial substances in
      eccrine glands of porcine snout skin.
AB  - The distribution of sialic acids and antimicrobial products (lysozyme, IgA,
      lactoferrin, beta-defensin 2) as well as Rab3D in the eccrine glands of porcine
      snout skin was studied by sialoglycoconjugate histochemistry and
      immunohistochemistry. The secretory epithelium consisted of two types of
      secretory cells: dark and clear cells. The dark cells exhibited considerable
      amounts of sialoglycoconjugates, which included O-acetylated sialic acids,
      whereas sialic acids in the sequence Siaalpha2-3Gal1-4GlcNAc were confined to
      some of the dark cells. All antimicrobial substances and Rab3D were demonstrated
      to be also mainly present in some of the dark cells. Additionally, in the
      cytological and cytochemical features, the different characteristics were
      observed among the dark cells. The results obtained are discussed with regard to
      the functional significance of the eccrine glands. The secretory products
      elaborated by this gland type may function as protective agents in order to
      preserve the skin integrity of the snout region, considering that sialic acids
      and antimicrobial substances are important in general defense mechanisms.

PMID- 22472895
TI  - NADPH-d activity in rat thymus after the application of retinoid acid.
AB  - The aim of this work was to determine the localization of nicotinamide-adenine
      dinucleotide phosphate-diaphorase (NADPH-d) activity as the marker for synthesis
      of nitric oxide synthase (NOS) in the rat thymus after the application of
      retinoid acid (RA) on 1st, 7th, 14th and 21st days of gestation. The given
      results can build the basis for understanding of the role of NOS in rat thymus.
      NADPH-d positive cells were represented with dark-blue color and were localized
      on corticomedullar junction of the thymus. These cells were of different
      intensity of coloring and were shaped in oval, circle or irregular forms. NADPH-d
      positive nerve fibers were observed in perivascular topography. They were marked
      more strongly in the case of control group. The result of application of RA to
      gravid rats was that the birth weights of newborn rats and their thymuses were
      smaller, but without statistically significance.

PMID- 22472896
TI  - Mena, a new available marker in tumors of salivary glands?
AB  - Mena (mammalian Ena) is an actin regulatory protein involved in cell motility and
      adhesion. Based on its potential role in malignant transformation revealed in
      other organs, we analyzed the Mena expression in normal salivary glands (SG) and
      salivary tumors. Mena expression was determined in normal SG (n=10) and also
      benign (n=20) and malignant (n=35) lesions of SG. For the immunohistochemical
      staining we used the anti-Mena antibody. All normal SG and the benign lesions (10
      pleomorphic adenomas, 10 Warthin's tumors) were Mena negative. Salivary duct
      carcinomas (n=5), carcinomas in pleomorphic adenoma (n=5), acinic cell carcinomas
      (n=5), squamous cell carcinomas (n=10) and high-grade mucoepidermoid carcinomas
      (n=2) were positive. The lymphomas (n=5) and low-grade mucoepidermoid carcinomas
      (n=1) were Mena negative. In one case the lymphoblastic cells stained positive
      for Mena. Some of the endothelial cells, in the peritumoral vessels, were Mena
      positive. To the best of our knowledge, this is the first study in the literature
      about Mena expression in salivary tumors. Our study suggests that Mena protein
      seems to play a role in malignant transformation and its intensity is correlated
      with the type and grade of tumor and also with vascular invasion. Its positivity
      in endothelial cells may suggest its potential role in tumor angiogenesis.

PMID- 22472897
TI  - PARP-1 protein  expression in glioblastoma multiforme.
AB  - One of the most common type of primary brain tumors in adults is the glioblastoma
      multiforme (GBM) (World Health Organization grade IV astrocytoma). It is the most
      common malignant and aggressive form of glioma and it is among the most lethal
      ones. Poly (ADP-ribose) polymerase 1 (PARP-1) gene, located to 1q42, plays an
      important role for the efficient maintenance of genome integrity. PARP-1 protein
      is required for the apoptosis-inducing factor (AIF) translocation from the
      mitochondria to the nucleus. PARP-1 is proteolytically cleaved at the onset of
      apoptosis by caspase-3. Microarray analysis of PARP-1 gene expression in more
      than 8,000 samples revealed that PARP-1 is more highly expressed in several types
      of cancer compared with the equivalent normal tissues. Overall, the most
      differences in PARP-1 gene expression have been observed in breast, ovarian,
      endometrial, lung, and skin cancers, and non-Hodgkin's lymphoma. We evaluated the
      expression of PARP-1 protein in normal brain tissues and primary GBM by
      immunohistochemistry. Positive nuclear PARP-1 staining was found in all samples
      with GBM, but not in normal neurons from controls (n=4) and GBM patients (n=27).
      No cytoplasmic staining was observed in any sample. In conclusion, PARP-1 gene is
      expressed in GBM. This finding may be envisioned as an attempt to trigger
      apoptosis in this tumor, as well as in many other malignancies. The presence of
      the protein exclusively at the nucleus further support the function played by
      this gene in genome integrity maintenance and apoptosis. Finally, PARP-1 staining
      may be used as GBM cell marker.

PMID- 22472903
TI  - Stress, cortisol, and nighttime blood pressure dipping in nonhypertensive Black
      American women.
AB  - Black American women have among the highest hypertension (HTN) rates in the
      world. Research suggests that nighttime might be a critical period of
      vulnerability for the development of HTN in Blacks. In the present study,
      personal factors (age, body fat, income, family history), psychological factors
      (stress, emotions, and John Henryism), and physiological factors (salivary
      cortisol and blood pressure [BP]) were explored in 30 Black women, ages 26-51
      years. Data were collected in participants' homes. BP was monitored while
      participants were awake and asleep. Cortisol samples were obtained within the
      first hour after awakening. The usual pattern for BP is a drop or dipping of 10
      20% during sleep; however, the BP for about a third of the subjects did not dip
      adequately during sleep. Though not statistically significant, this nondipping
      was clinically relevant and was associated with positive family history of HTN,
      more stress, lower positive and higher negative affect scores, and higher early
      morning cortisol levels. These findings add to the HTN risk profile and support
      the need to further explore the relationship between nondipping nighttime BP and
      cardiovascular disease in Black women.

PMID- 22472904
TI  - Sleep quality in nurses: a randomized clinical trial of day and night shift
      workers.
AB  - The study investigated the number of days off nurses working night shifts need to
      recover their sleep quality to the level of daytime workers during their days
      off. This study included 30 day-shift nurses and 32 night-shift nurses. It was
      conducted as a randomized clinical trial in the medical and surgical wards of a
      medical center in northern Taiwan in May and June 2010 using sleep diaries and
      sleep parameters collected by actigraphy on different workdays and days off. On
      workdays, the night-shift group had significantly less total sleep time (TST) on
      Day 5 and significantly lower sleep efficiency (SE) on Day 3 than the day-shift
      group. TSTs of the two groups on days off were higher than those on workdays. On
      the 4th consecutive day off, higher TST, a decrease in WASO, and an increase in
      SE suggests that the night-shift group had recovered their sleep quality to the
      level of the day-shift group on their days off. The SE of the night-shift group
      exceeded that of the day-shift group after the 4th consecutive day off, though
      the difference was not statistically significant in the present study. Based on
      these data, it is recommended that night-shift workers arrange a period of at
      least 4 days off after 5 consecutive night shifts and at least 5 days off if the
      staff who have previously worked night shifts are being assigned a set of
      different shifts.

PMID- 22472905
TI  - Effects on postoperative salivary cortisol of relaxation/music and patient
      teaching about pain management.
AB  - The physiological and psychological stress of surgery and postoperative pain can
      leave patients more susceptible to infection and complications. The present study
      was designed to determine whether two interventions, patient teaching (PT) for
      pain management and relaxation/music (RM), reduced cortisol levels, an indicator
      of stress, following abdominal surgery. Patients (18-75 years) were randomly
      assigned to receive PT, RM, a combination of the two, or usual care; the 205
      patients with both pre- and posttest cortisol values were analyzed. A 2 * 2
      factorial design was used to compare groups for PT effects and RM effects. Stress
      was measured by salivary cortisol before and after 20-min tests of the
      interventions in the morning and afternoon of postoperative Day 2. Saliva was
      stimulated with lemon juice and analyzed with high-sensitivity salivary cortisol
      enzyme immunoassay. Comparisons using analysis of covariance (ANCOVA),
      controlling for baseline levels, showed no PT effect or RM effect on cortisol in
      the morning or afternoon. Post hoc ANCOVA showed no significant effects when
      intervention groups were compared to the control group. Although in previous
      studies, RM reduced pain and music reduced cortisol on Day 1, in the present
      study the cortisol response to surgery was not attenuated by PT or RM on Day 2.
      The RM intervention can be used for pain but needs to be further tested for
      effects on plasma cortisol in abdominal surgery patients on their first
      postoperative day.

PMID- 22472906
TI  - Endogenous glucocorticoids inhibit myocardial inflammation induced by
      lipopolysaccharide:  involvement of regulation of histone deacetylation.
AB  - Emerging evidence indicates that myocardial inflammation plays a key role in the
      pathogenesis of cardiac diseases. But the exact mechanisms for this chronic
      inflammatory disorder have not been elucidated. Glucocorticoids (GCs) are the
      most effective anti-inflammatory treatments available for many inflammatory
      diseases. However, it is unknown whether endogenous GCs are able to exert anti
      inflammatory effect on myocardial inflammation. In this study, the potential role
      of endogenous GCs in the regulation of myocardial inflammation was investigated.
      We showed that the reduction of endogenous GC level by adrenalectomy promoted the
      production of basal and lipopolysaccharide (LPS)-induced proinflammatory
      cytokines, which could be partly reversed by supplementing with exogenous
      physiological level of hydrocortisone. Inhibition of GC receptor (GR) signaling
      pathway with GR antagonist mifepristone (RU486) or histone deacetylase inhibitor
      trichostatin A (TSA) also increased the levels of basal and LPS-induced
      proinflammatory cytokines. Moreover, blockade of GC-GR signaling pathway by
      adrenalectomy, RU486 or TSA enhanced LPS-induced myocardial nuclear factor-kappaB
      activation and histone acetylation but inhibited myocardial histone deacetylase
      expression and activity. Cardiac function studies demonstrated that blockade of
      the GC-GR signaling pathway aggravated inflammation-induced cardiac dysfunction.
      These findings indicate that endogenous GCs are able to inhibit myocardial
      inflammation induced by LPS. Endogenous GCs represent an important endogenous
      anti-inflammatory mechanism for myocardium in rats and such mechanism injury may
      be an important factor for pathogenesis of cardiac diseases.

PMID- 22472907
TI  - Regulation of autophagy by metabolic and stress signaling pathways in the heart.
AB  - Autophagy is an essential process for the maintenance of cellular homeostasis in
      the heart under both normal and stress conditions. Autophagy is a key degradation
      pathway and acts as a quality control sensor. It protects myocytes from cytotoxic
      protein aggregates and dysfunctional organelles by quickly clearing them from the
      cell. It also responds to changes in energy demand and mechanical stressors to
      maintain contractile function. The autophagic-lysosomal pathway responds to serum
      starvation to ensure that the cell maintains its metabolism and energy levels
      when nutrients run low. In contrast, excessive activation of autophagy is
      detrimental to cells and contributes to the development of pathological
      conditions. A number of signaling pathways and proteins regulate autophagy. These
      include the 5'-AMP-activated protein kinase/mammalian target of rapamycin
      pathway, FoxO transcription factors, Sirtuin 1, oxidative stress, Bcl-2 family
      proteins, and the E3 ubiquitin ligase Parkin. In this review, we will discuss how
      this diverse cast of characters regulates the important autophagic process in the
      myocardium.

PMID- 22472908
TI  - Comparison of the safety, tolerability, and pharmacokinetic profile of a single
      oral dose of pitavastatin 4 mg in adult subjects with severe renal impairment not
      on hemodialysis versus healthy adult subjects.
AB  - Pitavastatin is a novel statin recently approved in the United States as an
      adjunctive therapy with diet to reduce elevated total cholesterol, low-density
      lipoprotein cholesterol, apolipoprotein B, and triglycerides and to increase high
      density lipoprotein cholesterol. This open-label study enrolled 16 subjects as
      follows: group A: 8 adult subjects with severe renal impairment who were not on
      hemodialysis (estimated glomerular filtration rate of 15-29 mL/min/1.73 m2) and
      group B: 8 healthy adult subjects (estimated glomerular filtration rate >=80
      mL/min/1.73 m2). On day 1, the subjects received a single oral dose of
      pitavastatin 4 mg and remained in the clinic on days 1-3 for safety and
      pharmacokinetic assessments. Comparing group A with group B, the geometric mean
      ratio of AUC(0-inf) for pitavastatin was 1.36 (90% confidence interval, 0.88
      2.11). For Cmax, the corresponding ratio was 1.18 (90% confidence interval, 0.68
      2.02). There were no severe treatment-emergent adverse events (AEs), serious AEs,
      deaths, or treatment-emergent AEs leading to study drug discontinuation. A single
      dose of pitavastatin 4 mg was safe and well tolerated by the subjects in this
      study with severe renal impairment, who were not on hemodialysis.

PMID- 22472910
TI  - Chaperonin GroEL a Brucella immunodominant antigen identified using Nanobody and
      MALDI-TOF-MS technologies.
AB  - The deployment of today's antibodies that are able to distinguish Brucella from
      the closely similar pathogens, such as Yersinia, is still considered a great
      challenge since both pathogens share identical LPS (lipopolysaccharide) O-ring
      epitopes. In addition, because of the great impact of Brucella on health and
      economy in many countries including Syria, much effort is going to the
      development of next generation vaccines, mainly on the identification of new
      immunogenic proteins of this pathogen. In this context, Brucella-specific
      nanobodies (Nbs), camel genetic engineered heavy-chain antibody fragments, could
      be of great value. Previously, a large Nb library was constructed from a camel
      immunized with heat-killed Brucella. Phage display panning of this 'immune'
      library with Brucella total lysate resulted in a remarkable fast enrichment for a
      Nb referred to as NbBruc02. In the present work, we investigated the main
      characteristics of this Nb that can efficiently distinguish under well-defined
      conditions the Brucella from other bacteria including Yersinia. NbBruc02 showed a
      strong and specific interaction with its antigen within the crude lysate as
      tested by a surface plasmon resonance (SPR) biosensor and it was also able to
      pull down its cognate antigen from such lysate by immuno-capturing. Using matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS), NbBruc02 specific antigen was identified as chaperonin GroEL, also known as
      heat shock protein of 60 kDa (HSP-60), which represents a Brucella immunodominant
      antigen responsible of maintaining proteins folding during stress conditions.
      Interestingly, the antigen recognition by NbBruc02 was found to be affected by
      the state of GroEL folding. Thus, the Nb technology applied in the field of
      infectious diseases, e.g. brucellosis, yields two outcomes: (1) it generates
      specific binders that can be used for diagnosis, and perhaps treatment, and (2)
      it identifies the immunogenic candidate antigens for developing vaccines.

PMID- 22472909
TI  - Autophagy, myocardial protection, and the metabolic syndrome.
AB  - Autophagy is a housekeeping process that helps to maintain cellular energy
      homeostasis and remove damaged organelles. In the heart, autophagy is an adaptive
      process that is activated in response to stress including acute and chronic
      ischemia. Given the evidence that autophagy is suppressed in energy-rich
      conditions, the objective of this review is to examine autophagy and
      cardioprotection in the setting of the metabolic syndrome. Clinical approaches
      that involve the induction of cardiac autophagy pharmacologically to enhance the
      heart's tolerance to ischemia are also discussed.

PMID- 22472911
TI  - Lanthanide-assisted NMR evaluation of a dynamic ensemble of oligosaccharide
      conformations.
AB  - A novel methodology is presented for evaluating a dynamic ensemble of
      oligosaccharide conformations by lanthanide-assisted NMR spectroscopy combined
      with molecular dynamics (MD) simulations. The results obtained using the GM3
      trisaccharide demonstrated that pseudocontact shift measurements offer a valuable
      experimental tool for the validation of MD simulations of highly flexible
      biomolecules.

PMID- 22472912
TI  - Free volume and phase transitions of 1-butyl-3-methylimidazolium based ionic
      liquids from positron lifetime spectroscopy.
AB  - Positron annihilation lifetime spectroscopy (PALS) was used to study a series of
      ionic liquids (ILs) with the 1-butyl-3-methylimidazolium cation ([C4MIM](+)) but
      different anions [Cl](-), [BF4](-), [PF6](-), [OTf](-), [NTf2](-), and
      [B(hfip)4](-) with increasing anion volumes. Changes of the ortho-positronium (o
      Ps) lifetime parameters with temperature were observed for crystalline and
      amorphous (glass, supercooled, and normal liquid) states. Evidence for distinct
      phase transitions, e.g. melting, crystallization and solid-solid transitions, was
      observed in several PALS experiments. The o-Ps mean lifetime tau3 showed smaller
      values in the crystalline phase due to dense packing of the material compared to
      the amorphous phase. The o-Ps lifetime intensity I3 in the liquid state is
      clearly smaller than in the crystallized state. This behaviour can be attributed
      to a solvation of e(+) by the anions, which reduces the Ps formation probability
      in the normal and supercooled liquid. These phenomena were observed for the first
      time when applying the PALS technique to ionic liquids by us in one preliminary
      and in this work. Four of the ionic liquids investigated in this work ([BF4](-),
      [NTf2](-), [PF6](-) and [Cl](-) ILs) exhibit supercooled phases. The specific
      hole densities and occupied volumes of those ILs were obtained by comparing the
      local free volume with the specific volume from pressure-volume-temperature (PVT)
      experiments. From the o-Ps lifetime, the mean size vh of free volume holes of the
      four samples was calculated and compared with that calculated according to
      Furth's hole theory. The hole volumes from both methods agree well. From the
      Cohen-Turnbull fitting of viscosity and conductivity against PALS/PVT results,
      the influence of the free volume on molecular transport properties was
      investigated. 

PMID- 22472914
TI  - Tables or bar graphs? Presenting test results in electronic medical records.
AB  - BACKGROUND: Electronic personal health records offer a promising way to
      communicate medical test results to patients. We compared the usability of tables
      and horizontal bar graphs for presenting medical test results electronically.
      METHODS: We conducted experiments with a convenience sample of 106 community
      dwelling adults. In the first experiment, participants viewed either table or bar
      graph formats (between subjects) that presented medical test results with normal
      and abnormal findings. In a second experiment, participants viewed table and bar
      graph formats (within subjects) that presented test results with normal,
      borderline, and abnormal findings. RESULTS: Participants required less viewing
      time when using bar graphs rather than tables. This overall difference was due to
      superior performance of bar graphs in vignettes with many test results. Bar
      graphs and tables performed equally well with regard to recall accuracy and
      understanding. In terms of ease of use, participants did not prefer bar graphs to
      tables when they viewed only one format. When participants viewed both formats,
      those with experience with bar graphs preferred bar graphs, and those with
      experience with tables found bar graphs equally easy to use. Preference for bar
      graphs was strongest when viewing tests with borderline results. CONCLUSIONS:
      Compared to horizontal bar graphs, tables required more time and experience to
      achieve the same results, suggesting that tables can be a more burdensome format
      to use. The current practice of presenting medical test results in a tabular
      format merits reconsideration.

PMID- 22472915
TI  - Do different methods of modeling statin treatment effectiveness influence the
      optimal decision?
AB  - PURPOSE: Modeling studies that evaluate statin treatment for the prevention of
      cardiovascular disease (CVD) use different methods to model the effect of
      statins. The aim of this study was to evaluate the impact of using different
      modeling methods on the optimal decision found in such studies. METHODS: We used
      a previously developed and validated Monte Carlo-Markov model based on the
      Rotterdam study (RISC model). The RISC model simulates coronary heart disease
      (CHD), stroke, cardiovascular death, and death due to other causes. Transition
      probabilities were based on 5-year risks predicted by Cox regression equations,
      including (among others) total and high-density lipoprotein (HDL) cholesterol as
      covariates. In a cost-effectiveness analysis of implementing the ATP-III
      guidelines, we evaluated the impact of using 3 different modeling methods of
      statin effectiveness: 1) through lipid level modification: statins lower total
      cholesterol and increase HDL cholesterol, which through the covariates in the Cox
      regression equations leads to a lower incidence of CHD and stroke events; 2)
      fixed risk reduction of CVD events: statins decrease the odds of CHD and stroke
      with an associated odds ratio that is assumed to be the same for each individual;
      3) risk reduction of CVD events proportional to individual change in low-density
      lipoprotein (LDL) cholesterol: the relative risk reduction with statin therapy on
      the incidence of CHD and stroke was assumed to be proportional to the absolute
      reduction in LDL cholesterol levels for each individual. The probability that the
      ATP-III strategy was cost-effective, compared to usual care as observed in the
      Rotterdam study, was calculated for each of the 3 modeling methods for varying
      willingness-to-pay thresholds. RESULTS: Incremental cost-effectiveness ratios for
      the ATP-III strategy compared with the reference strategy were ?56,642/quality
      adjusted life year (QALY), ?21,369/QALY, and ?22,131/QALY for modeling methods 1,
      2, and 3, respectively. At a willingness-to-pay threshold of ?50,000/QALY, the
      probability that the ATP-III strategy was cost-effective was about 40% for
      modeling method 1 and more than 90% for both methods 2 and 3. Differences in
      results between the modeling methods were sensitive to both the time horizon
      modeled and age distribution of the target POPULATION:  CONCLUSIONS: Modeling the
      effect of statins on CVD through the modification of lipid levels produced
      different results and associated uncertainty than modeling it directly through a
      risk reduction of events. This was partly attributable to the modeled effect of
      cholesterol on the incidence of stroke.

PMID- 22472916
TI  - Impact of program scale and indirect effects on the cost-effectiveness of
      vaccination programs.

PMID- 22472917
TI  - Risk factors for colonic diverticular hemorrhage: Japanese multicenter study.
AB  - BACKGROUND AND AIM: Diverticular hemorrhage is the common cause of lower
      gastrointestinal bleeding, and its incidence has been increasing in Japan.
      However, the exact cause of diverticular hemorrhage is not well understood. We
      investigated the risk factors for diverticular hemorrhage. METHODS: We selected
      103 patients with diverticular hemorrhage as cases and patients with colonic
      diverticulosis without a history of bleeding were selected as control subjects,
      exactly matched for age and gender. We collected the data from the medical
      records of each of the patients, such as those related to the comorbidities,
      medications and findings of colonoscopy, and conducted a matched case-control
      study to analyze the risk factors for diverticular hemorrhage. RESULTS: Both
      groups were composed of 75 men and 28 women. The median age of the patients in
      both groups was 72.0 years (47.0-87.0). The body weight (p = 0.0065), body mass
      index (p = 0.006), prevalence of hypertension (p = 0.0242), prevalence of
      ischemic heart disease (p = 0.0015), and frequency of use of low-dose aspirin (p
      = 0.042) were significantly different between the two groups. The percentage of
      patients with bilateral diverticula, that is, diverticula on both the right and
      left hemicolon, was significantly higher in the diverticular hemorrhage group (p
      = 0.0011). Multiple regression analysis identified only the diverticular location
      as being significantly associated with the risk of diverticular hemorrhage (p =
      0.0021). CONCLUSIONS: Only the diverticular location (bilateral) was found to be
      an independent risk factor for diverticular hemorrhage.

PMID- 22472924
TI  - Review of comparative studies between bone densitometry and quantitative
      ultrasound of the calcaneus in osteoporosis.
AB  - OBJECTIVE: To assess the utility of quantitative ultrasound (QUS) of the
      calcaneus for diagnosing osteoporosis compared to the gold standard, bone
      densitometry using dual-emission X-ray absorptiometry (DXA), according to
      published reports. DESIGN: In this systematic review, the Medline/PUBMED, Medline
      Ovid and Journals@Ovid, and Wilson General Sciences Full Text database were used.
      The search strategy involved use of the following MeSH descriptors: [osteoporosis
      AND (densitometry OR ultrasonography)], and 39 articles published between 2001
      and April 2010 were assessed. However, only six articles met the inclusion
      criteria: sensitivity and specificity of QUS, sample (women or men with no
      treatment or other disease likely to change bone mass index), devices used,
      comparative T-score between QUS of the calcaneus and DXA. The GE-Lunar Achilles
      and Hologic Sahara devices were used in most of the tests reported and were
      effective. RESULTS: All studies assessed compared QUS of the calcaneus to DXA of
      the lumbar spine or femoral neck, as the gold standard. QUS sensitivity ranged
      from 79% to 93% and specificity ranged from 28% to 90% when at the lower
      threshold. It is a controversial parameter, because the gold-standard threshold
      (T-score < -2.5, DXA) could not be used for QUS without errors in osteoporosis
      diagnosis. All studies had a threshold determined by the authors' criteria, with
      a variability of -1.7 (pDXA T--score) and -2.4 for QUS, leading to the same
      prevalence of osteoporosis, and a T-score of < -3.65 for QUS was equivalent to a
      T-score < -2.5 for DXA. CONCLUSIONS: Based on the analysis of seven studies, we
      conclude that QUS of the calcaneus still cannot be used to confirm diagnosis of
      osteoporosis by comparing the results to those of patients who had already
      received such a diagnosis based on DXA. However, further research should be
      conducted in this area, because it is possible to improve the number diagnoses by
      varying the cutoff T-score. Furthermore, using QUS of the calcaneus was a helpful
      tool for assessing pathological fractures, whether or not they were associated
      with osteoporosis.

PMID- 22472925
TI  - Frequency of rheumatic diseases in Portugal: a systematic review.
AB  - OBJECTIVES: To describe the frequency of rheuma-tic diseases in Portugal through
      a systematic review of published literature, critically appraising available
      information and identifying data collection gaps. METHODS: We systematically
      reviewed the literature to retrieve data on the occurrence of rheumatic diseases
      in Portugal through MEDLINE and Index das Revistas Medicas Portuguesas searches,
      PhD theses, and national health surveys reports. Original articles in English or
      Portuguese published between 1 January 2000 and 31 December 2010 were included.
      RESULTS: We retrieved information for the prevalence of rheumatic diseases,
      osteoarthritis, back pain, work-related musculoskeletal disorders (WRMDs),
      osteoporosis, fibromyalgia, rheumatoid arthritis, spondyloarthritis and other
      systemic rheumatic diseases and for the incidence of back pain, osteoporotic
      fracture and other systemic rheumatic diseases. The prevalence of rheumatic
      diseases ranged from 16.0% to 24.0% and the prevalence of osteoarthritis was
      11.1% (95% confidence intervals (95%CI): 9.4-13.1) in the knee and 5.5% (95%CI:
      4.3-7.0) in the hip. Regarding back pain, period prevalence ranged from 8.0%
      (95%CI: 6.1-10.1) to 29.5% (95%CI: 23.4-36.2) in children and from 12.3% (95%CI:
      10.5-14.3) to 51.3% (95%CI: 48.6-53.9) in adults. The prevalence of WRMDs ranged
      from 5.9% to 84.2% (95%CI: 80.8-87.3). The yearly incidence of osteoporotic
      fracture (per 100 000) ranged from 93.3 to 481 (95%CI: 407-564) in women and from
      31.9 to 154 (95%CI: 106-218) in men. The prevalence of osteoporosis in women
      ranged from 11.0% to 15.4% (95%CI: 13.4-17.6) and in men from 1.1% to 16.8%
      (95%CI: 12.2-22.3). The prevalence of fibromyalgia ranged from 3.6% (95%CI: 2.0
      5.2) to 3.7% (95%CI: 2.0-5.4). The prevalence estimates of ankylosing spondylitis
      and of spondyloarthritis were 0.6% and 1.6% (95%CI: 0.8-2.7), respectively. The
      prevalence of systemic lupus erythematosus was estimated in 0.2% (95%CI: 0.1
      0.8). CONCLUSIONS: There is a broad spectrum of information available that
      indicates an important burden of rheumatic diseases in the general Portuguese
      population. Gaps were identified particularly regarding inflammatory
      arthropathies and other systemic rheumatic diseases.

PMID- 22472926
TI  - Fatigue in rheumatoid arthritis: association with severity of pain, disease
      activity and functional status.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease characterized by
      chronic symmetric polyarthritis causing progressive joint destruction and
      disability. Major patient complaints are pain, disability and fatigue. The aim of
      this study is to assess fatigue and its association with disease-specific
      variables (severity of pain, disease activity, and functional status) in patients
      with RA. PATIENTS AND METHODS: A total of 160 RA patients were included in the
      study. Fatigue was measured by using Fatigue Symptom Inventory (FSI). The
      quadrivariate Disease Activity Score-28 (DAS28) was used for evaluating disease
      activity and Health Assessment Questionnaire (HAQ) for determining functional
      status. Severity of pain was measured by using 10 cm Visual Analog Scale-Pain
      (VAS-pain). RESULTS: Intensity items of FSI (most fatigue, least fatigue, average
      fatigue, current fatigue) were strongly correlated with DAS28, HAQ, and VAS pain
      (p=0.000). When the correlation coefficients were analyzed, current fatigue
      showed the highest correlation with VAS-pain (r: 0.96). This was followed by
      DAS28 and HAQ, respectively (r: 0.77 and 0.70) (p=0.000). Duration items of FSI
      (number of days fatigued, amount of time fatigued) were significantly correlated
      with DAS28, HAQ, and VAS pain (p=0.000). Also there were significant positive
      correlations between interference scale of FSI and DAS28, HAQ, and VAS-pain (r:
      0.68, 0.61 and 0.67, respectively) (p=0.000). None of FSI subgroups showed
      statistically significant correlation with di-sease duration. CONCLUSIONS:
      Fatigue is strongly associated with severity of pain, disease activity and
      functional status. Fatigue should be included in clinical practice and clinical
      trials as a RA outcome measure.

PMID- 22472927
TI  - Markers of progression to rheumatoid arthritis: discriminative value of the new
      ACR/EULAR rheumatoid arthritis criteria in a Portuguese population with early
      polyarthritis.
AB  - OBJECTIVES: Our goal was to test the performance of the new American College of
      Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for the
      classification of rheumatoid arthritis (RA) in a cohort of patients with very
      recent onset polyarthritis. PATIENTS: Untreated polyarthritis patients with less
      than 6 weeks of duration were enrolled. All patients were followed-up in order to
      establish a definitive diagnosis. RESULTS: Thirty-seven patients were included.
      During the follow up 57% of the patients evolved to RA. The median age of the RA
      group patients was simi-lar to the median age of the non-RA group [median (IQR)
      47 (31-58.5) vs 43 (34-69) years, p=0.74]. At the initial visit the DAS 28 in the
      RA group was significantly higher than in the non-RA group, as well as the visual
      analogue scale (VAS), the HAQ and the number of swollen joints. Among the 21 RA
      patients, 43% presented RF and 28.6% presented anti-citrullinated protein
      antibody (ACPA) in the first visit. RF and ACPA were not detectable in any of the
      patients who did not evolve to RA. According to the new ACR/EULAR criteria, the
      mean total score of the RA group at baseline was significantly higher than the
      non-RA group [median (IQR) 6 (4.5-8) vs 4.5 (2.2-6), p=0.007]. CONCLUSION: In our
      cohort high DAS28, swollen joint count, VAS and HAQ and the presence of RF or
      ACPA were eventually associated with the evolution into RA. The new ACR/EULAR
      criteria for the classification of RA seem to perform well in very early RA.

PMID- 22472928
TI  - Patients' satisfaction with the rheumatology day care unit.
AB  - BACKGROUND: Patients receiving biological therapies are regularly evaluated and
      monitored at rheumatology day care units (RDCU). Despite patients' satisfaction
      with the delivered care and the relationship between the patient and the
      multidisciplinary team being acknowledged as important aspects to ensure
      adherence to therapy, factors associated with them have not been investigated so
      far. OBJECTIVES: To evaluate patients' satisfaction with the functioning of the
      RDCU and to identify the factors associated with the level of satisfaction.
      METHODS: An anonymous questionnaire was administered to all patients with
      rheumatoid arthritis (RA) or spondyloarthritis treated with biological drugs and
      followed at the RDCU at Hospital Garcia de Orta, Almada, Portugal. Satisfaction
      was measured using a visual analogue scale (0-100, 0 meaning completely
      unsatisfied, 100 meaning completely satisfied). Further information was collected
      on socio-demographic variables, physical conditions of the RDCU, waiting time,
      satisfaction with the role of medical, nursing and administrative staff
      (satisfaction level with their friendliness, question answering, care delivery,
      privacy during consultation, clarity in the information given, which was then
      transformed into a composite score, 0-20). Factors associated with satisfaction
      were studied by univariable followed by multiple linear regression to adjust for
      potential confounders. RESULTS: In total, 150 patients were included in the study
      (mean age 50.6 +/- 13.7 years, 64% female, 62% RA, mean disease duration 10.6 +/-
      6.1 years). The majority of patients attended the RDCU for more than three years
      and 57% received subcutaneous therapy. The mean level of satisfaction with the
      RDCU was 81.9 +/- 17.9. Multivariable analysis showed that intravenous therapy
      (beta 6.13, 95% confidence interval - CI 0.71-11.55), physician score (beta 2.28,
      95%CI 1.20-3.35) and increasing levels of satisfaction with the room temperature
      (beta 5.64, 95%CI 3.06-8.21) and waiting time (beta 25.53, 95%CI 8.17-42.89, for
      a very good vs non-acceptable waiting time) were positively associated with the
      level of satisfaction, while the nursing score was inversely associated.
      CONCLUSIONS: Patients were overall very satisfied with the functioning of the
      RDCU. Waiting time, satisfaction with the physician role, room temperature and
      intravenous therapy were the main factors positively associated with the level of
      satisfaction.

PMID- 22472930
TI  - [Practical guide for the use of biological agents in rheumatoid arthritis -
      December 2011 update].
AB  - The authors review the practical aspects of biological therapy use for rheumatoid
      arthritis patients, commenting safety issues before and after treatment
      initiation and the best treatment strategies to optimize efficacy.

PMID- 22472931
TI  - [Spontaneous regression of symptomatic lumbar disc herniation].
AB  - Lumbar disc herniation is very common, sometimes leading to disability of the
      patient, and in a significant number of cases can only be solved with surgery.
      This paper reports a case with a large symptomatic disc herniation, which
      suffered spontaneous regression, and no surgery was necessary. The case is
      documented on serial MRI, consistent with the clinical improvement of the
      patient.

PMID- 22472929
TI  - Portuguese guidelines for the use of biological agents in rheumatoid arthritis -
      October 2011 update.
AB  - The authors present the revised version of the Portuguese Society of Rheumatology
      (SPR) guidelines for the treatment of Rheumatoid Arthritis (RA) with biological
      therapies. In these guidelines the criteria for introduction and maintenance of
      biological agents are discussed as well as the contraindications and procedures
      in the case of nonresponders. Biological treatment (with a tumour necrosis factor
      antagonist, abatacept or tocilizumab) should be considered in RA patients with a
      disease activity score 28 (DAS 28) equal to or greater than 3.2 despite treatment
      with at least 20mg-weekly-dose of methotrexate (MTX) for at least 3 months or, if
      such treatment is not possible, after 3 months of other conventional disease
      modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a
      significant functional or radiological deterioration under treatment with
      conventional regimens could also constitute an indication for biological
      treatment. The treatment goal should be remission or, if that is not achievable,
      at least a low disease activity, defined by a DAS28 lower than 3.2, without
      significative functional or radiological worsening. The response criteria, at the
      end of the first 3 months of treatment, are a decrease of at least 0.6 in the
      DAS28 score. After 6 months of treatment res-ponse criteria is defined as a
      decrease greater than 1.2 in the DAS28 score. Non-responders, in accordance to
      the Rheumatologist's clinical opinion, should try a switch to another biological
      agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

PMID- 22472932
TI  - [A case of acroparesthesias, asthenia and fever. A new mutation in Fabry's
      disease].
AB  - Fabry disease is an X-linked hereditary metabolic storage disorder, due to the
      deficiency in lysosomal alpha-galactosidase A, with the consequent
      glycosphingolipids accumulation, primarily globotriaosylceramide, at cellular
      level. Multiorganic involvement occurs progressively, leading to severe
      manifestations and even premature mortality. We describe a case of a 20 year-old
      man who was sent to Rheumatology because of inespecific symptoms that lasted for
      years, namely acroparesthesias and diffuse hand pain and autolimited flares of
      high fever and general muscular weakness. Despite denying cutaneous findings, a
      remarkable purplish-red rash of slightly raised angiectases in the lower trunk
      was present. This rash was diagnosed as angiokeratomas, and blood measurement of
      alpha-galactosidase A confirmed the suspicion of Fabry disease. He was referred
      to a rare disease consultation, where the evaluation revealed the presence of
      other characteristic findings, such as cornea verticilata and cerebral lacunar
      infarction sequelae. The authors want to remark the importance of physical
      examination in these cases of inespecific long-lasting symptoms, with no
      diagnosis and with functional impairment, and the importance of multidisciplinary
      evaluation and collaboration. We also highlight that this mutation was not as yet
      described.

PMID- 22472933
TI  - Association of systemic-onset juvenile idiopathic arthritis and celiac disease -
      a case report.
AB  - INTRODUCTION: In a 28-year period, 5508 patients were followed at our Paediatric
      Rheumatology Division and 712 (13%) patients had juvenile idiopathic arthritis
      (JIA) (ILAR criteria). One (0.14%) of them had association with celiac disease
      (CD), with predominance of gastrointestinal manifestations and this case was
      described herein. CASE REPORT: A 10-years-old female patient was hospitalized
      with persistent fever, weight loss, asthenia, anorexia and an evanescent pink
      macular rash. After one week, she presented arthritis of left knee and ankle with
      duration of 75 days. The initial laboratory exams revealed anemia and elevation
      of inflammatory markers. Immunological tests were positive for anti-endomysial
      antibodies IgA and anti-thyroglobulin antibody. The diagnosis of systemic JIA was
      established and indomethacin (2.0 mg/kg/day) was started with improvement of
      arthritis. The patient evolved with vomiting, diarrhea and abdominal pain and
      upper gastrointestinal barium study showed areas of small bowel dilatation and
      thickening of folds, suggestive of malabsorption syndrome. Colonoscopy was normal
      and small intestinal biopsy was compatible with CD. DISCUSSION: We reported a
      case of a rare association of early diagnosis of systemic JIA occurring
      simultaneously with CD. This study reinforces the importance of taking into
      account the possible association of organ-specific autoimmune diseases during JIA
      course.

PMID- 22472934
TI  - Systemic sclerosis, a rare case.
AB  - Systemic sclerosis (SS) is a rare severe autoimmune disease involving the
      connective tissue. The pathophysiology is not clearly understood. It is
      characterized by a remarkable clinical heterogeneity, and virtually all organs
      can be affected. Concerning diagnosis, the presence of antinuclear antibodies
      (ANA) can be found in more than 90% of patients, but the diagnosis is made
      gathering clinical manifestations, autoimmune panel, nailfold capillaroscopy and
      in some cases biopsy of the organ involved. The disease course is also weakly
      understood, although some serological patterns can be distinguished. Current
      therapeutic options target few aspects of pathologic mechanism and clinical
      management remains a challenge.The authors presented a rare case of a SS ANA
      negative, which demonstrates the diagnostic challenge of this disease.

PMID- 22472935
TI  - Adult-onset Still's disease misdiagnosed as pneumonia: two case reports.
AB  - Adult-onset Still disease (AOSD) is an uncommon inflammatory condition of unknown
      origin and pathogenesis. Pulmonary involvement is rare and includes pleuritis and
      transient radiological infiltrations. We report two cases of AOSD characterized
      by lung involvement at presentation. Both were misdiagnosed as pneumonia with
      para-pneumo-nic effusion. We also discuss the difficulties in diag-nosis of AOSD
      with pulmonary infiltration.

PMID- 22472936
TI  - Recurrent symphysitis pubis.

PMID- 22472937
TI  - The generation of spermatogonial stem cells and spermatogonia in mammals.
AB  - Spermatogenesis is a complex series of cellular changes leading to the formation
      of haploid male gametes (spermatozoa) and includes mitotic, meiotic and post
      meiotic phases. Spermatogonial stem cells (SSCs) are essential for the continuous
      lifelong production of spermatozoa. Spermatogenesis is initiated when SSC is
      triggered to undergo mitosis that gives rise to progenitors, which further
      differentiate into spermatogonia. In this review, we describe the origin of SSCs
      and other spermatogonia populations and summarize the knowledge concerning their
      markers.

PMID- 22472938
TI  - The effect of horse serum on in vitro development of porcine parthenogenetic
      embryos.
AB  - The objective of this study was to examine the effect of different sera and serum
      like substances on the preimplantation development of porcine parthenogenetic
      embryos. Chemically activated (calcium ionophore A23187+cytochalasin B) pig
      oocytes were pre-cultured for five days. On day 5, the parthenogenetic embryos
      were treated with porcine follicular fluid (PFF), fetal bovine serum (FBS), horse
      serum (HS) or porcine serum albumin (PSA), and were cultured two more days. Horse
      serum was found to be the most effective protein source in enhancing parthenote
      development judging by blastocyst formation and hatching. Next, three different
      concentrations of HS (10, 20 and 30%) were used to determine the optima HS
      concentration needed to improve the development of porcine parthenogenetic
      embryos. All HS concentrations increased the blastocyst cell number and decreased
      the incidence of blastocyst apoptotic cells with 20% being the most effective. In
      conclusion, horse serum enhanced parthenogenetic embryo development and the
      quality of porcine parthenogenetic embryos.

PMID- 22472939
TI  - Follicular populations, recruitment and atresia in the ovaries of different
      strains of mice.
AB  - Follicular atresia is a key event in the selection of the ovulatory follicles and
      occurs during all developmental stages. The aims of the study were to evaluate
      the follicular population as well as the rates of follicular recruitment and
      atresia in different strains of mice. Ovaries were obtained from four strains of
      mice: G1/ Swiss, G2/ F1 Swiss*C57BL/6, G3/ inbred strain C57BL/6, and G4/ F1
      C57BL/6*Swiss. All mice used in the study were 60 days old. Ovaries collected
      from the mice were fixed and processed for histological analysis. The G2 ovaries
      were also used to examine immunolocalization of active caspase-3. The pimordial
      follicle population was smaller in G3 mice than in G1, G2 and G4 groups (7 565+/
      1 845 vs. 17 180+/-3 159, 14 785+/-3 319 and 13 325+/-2 685, respectively;
      p<0.05). The rate of follicular recruitment in G3, however, was higher than in
      the other groups (29.2% vs. 18.2%, 17.3% and 13.0% in G1, G2 and G4,
      respectively; p<0.05), resulting in a similar (p>0.05) number of antral follicles
      among groups. The small follicular pool in G3 mice was also associated with a
      lower rate of follicular atresia (11.4% vs. 17.2%, 16.7% and 13.6% for G3, G1, G2
      and G4, respectively; p<0.05). The number of follicles stained with active
      caspase-3 was higher (p<0.05) during the final stage of preantral
      folliculogenesis than in other stages of follicular development suggesting that
      apoptosis in mice occurs earlier in comparison to large animals. Thus, it was
      concluded that differences in follicle reservoir among mice strains are
      compensated by an increased rate of follicular recruitment and a decreased rate
      of follicular atresia; and atresia occurs in mice mainly at the end of the
      preantral stage of folliculogenesis.

PMID- 22472940
TI  - Impact of protamine transcripts and their proteins on the quality and
      fertilization ability of sperm and the development of preimplantation embryos.
AB  - Protamine 1 (PRM1) and 2 (PRM2) are major nuclear proteins in spermatozoa known
      to bind to chromatin during early spermatogenesis. The aim of this study was to
      evaluate the impact of protamine transcripts and proteins on human spermatozoa
      and their fertilization ability as well as the development of preimplantation
      embryos. Oocytes selected from 92 patients were fertilized in vitro (IVF) using
      their partners' sperm after evaluating its concentration, motility and
      morphology. Reverse transcription and real-time quantitative PCR (RQ-PCR) were
      applied to determine protamine mRNA level, while sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were used to
      quantify the protamine protein concentration. Next, protamine mRNA and protein
      levels were correlated with sperm concentration, motility and morphology as well
      as with the fertilization ability of mature spermatozoa and embryos of different
      quality obtained from the IVF program. A significant correlation has been found
      between protamine transcripts/proteins and: sperm concentration, progressive
      sperm motility, sperm fertilization ability as well as embryo quality. Protamine
      transcripts and proteins contribute to the quality of spermatozoa, successful
      fertilization and may have a significant influence on the development of
      preimplantation embryos.

PMID- 22472941
TI  - Reproduction and fecundity of the golden loach, Sabanejewia baltica Witkowski,
      1994 from Bug River in Poland.
AB  - In this paper we report for the first time the results of histology of the golden
      loach (S. baltica) gonads (25 females and 8 males) and absolute fecundity of
      females from the Bug River during the reproductive season. The golden loach has
      an asynchronous ovary and spawns in batches. The absolute fecundity of the golden
      loach ranged from 1507 to 7220 eggs (3050+/-1377). We hypothesize that the golden
      loach spawns twice a year.

PMID- 22472942
TI  - The expression of aquaporin 1 and 5 in uterine leiomyomata in premenopausal
      women: a preliminary study.
AB  - The aim of this study was to investigate the expression of aquaporins (AQPs) in
      uterine tissues of premenopausal women. We demonstrated for the first time the
      expression of AQP1, AQP5 and AQP9 in uterine leiomyomata and in the adjacent
      normal endometrium and myometrium. The expression of AQP1 and 5 was higher in
      leiomyomata than in unaffected uteri. AQP9 was expressed only in the unaffected
      endometrium. It is possible that AQP1 and AQP5 contribute to the formation of
      leiomyomata in premenopausal women.

PMID- 22472943
TI  - Microarray screening for novel preeclampsia biomarker candidates.
AB  - INTRODUCTION: Our aim was to identify novel biomarker candidates for the near
      term prediction of preeclampsia in a homogenous collective. In this study, we
      screened at the genome-wide level for gene expression in placental villous tissue
      from patients with severe preeclampsia in comparison to normal healthy
      pregnancies. MATERIAL AND METHODS: Total RNA was extracted from placental villous
      tissue from 9 preeclamptic patients and 7 normotensive controls after scheduled
      cesarean sections. After sample pooling, gene expression analysis was performed
      using six Affymetrix Human Gene 1.0 ST arrays, followed by quantitative RT-PCR
      and validation of selected markers in the serum of patients at the protein level.
      RESULTS: In total, 896 significantly differentially expressed genes were
      identified (p <= 0.05). After restricting these to molecules present in the
      circulation, 9 upregulated and 5 downregulated genes were selected. Four of them
      (beta-hCG, HTRA4, LHB1, all upregulated; and NOX4, downregulated) were validated
      by quantitative real-time RT-PCR. Finally, the maternal plasma protein levels of
      2 of these genes (LHB and beta-hCG) were confirmed to be significantly different
      between preeclampsia cases and controls. DISCUSSION: We identified 14 potential
      new biomarker candidates for preeclampsia and validated 4 of them by quantitative
      RT-PCR and 2 of them with subsequent serum protein analyses. Further studies will
      assess the optimal marker combination for the imminent prediction of impending
      preeclampsia.

PMID- 22472945
TI  - Teasing out specific language impairment from an autism spectrum disorder.
AB  - CASE: Marcus is a handsome, sweet, 71/2-year-old boy with a significant history
      of delayed development, specifically in speech and language skills, as well as
      difficulties with social interactions that have led other specialists to be
      concerned about a diagnosis of an autism spectrum disorder.He has been seen in
      our primary care practice since birth. He was born full-term after vaginal
      delivery weighing 6 pounds, 6 ounces. There were no pregnancy or delivery
      complications noted. Genetic testing revealed normal chromosomes, fragile X, and
      microarray testing. Marcus was a picky eater and good sleeper and had delays in
      toilet training.There is no family history of attention-deficit hyperactivity
      disorder (ADHD), autism, or substance abuse. Maternal grandmother and mother have
      a history of learning difficulties, and his father and a paternal uncle have a
      history of depression and anxiety. Marcus lives in a supportive environment with
      his mother, father, and sister.Marcus was noted to have significantly delayed
      language, stuttering, and immediate echolalia as a toddler. Gross and fine motor
      milestones were met on time, but he did not talk or follow directions until 4 to
      5 years old. As a younger child, he would pretend to talk on the phone or mow the
      grass with a pretend lawn mower, but other household activities were not of
      interest to Marcus.Currently, he enjoys puzzles, reading, and board games. He
      likes to play with other children and can interact with familiar adults. Marcus
      is reported to initiate social interactions, although he has difficulty in
      understanding personal space. Imaginative play is preferred over other types. He
      seeks out adult attention and will bring objects over to an adult especially to
      share his perceived accomplishment. Marcus has difficulty in playing
      cooperatively with his sister.He is independent with activities of daily living.
      Marcus is noted to have auditory defensiveness including covering his ears to
      loud noises and becoming distressed. Parents feel he is immature and inattentive
      for his age. Marcus responds well when a routine is followed.Previous testing
      about 2 years ago revealed significant language deficits on the Clinical
      Evaluation of Language Functioning with average scores on the Woodcock Johnson
      Achievement Testing and Test of Nonverbal Intelligence Version 3. Marcus was not
      referred for early intervention and he did not attend preschool. In a regular
      education Kindergarten, he received speech and occupational therapy along with
      reading and math support.Comments from teachers or evaluator include the
      following: Marcus looked to his peers for clues about what he should be doing.
      Marcus has great difficulty in understanding requests but seems to be interested
      in pleasing his teacher and others. Marcus' language difficulty makes
      socialization with his peers problematic; however, he is interested in
      interacting with them and they seem to accept him willingly. Marcus has intent to
      communicate with others but relies on visual support to decipher social
      situations. Marcus has difficulty in attending to details and moves from activity
      to activity quickly. His short attention span is likely impacting not only
      learning but also his ability to socially interact with peers.On the day you see
      him for his 7-year-old checkup, he brought many toys over to show his father and
      interrupted your conversation to get your attention intermittently throughout the
      examination. He immediately pointed out a lit ceiling tile with Nemo illuminated
      to show his father. Marcus does not have any notable or significant repetitive
      motor mannerisms or stereotypies reported or observed. Marcus' gesture use was
      appropriate for age and included both symbolic (directing eye gaze and pointing)
      and concrete (hands up to be picked up and touching an item rather than pointing
      to it) gestures. Play observed today, although immature for age, was novel,
      imaginative, and functional. Answers to questions did not always match the
      question posed. He had a difficult time waiting for his turn before interrupting
      a conversation. Visual cues were helpful in understanding what was expected of
      him and what was going on socially.Marcus' speech is notable for persistent
      stuttering and difficulty in turn-taking in conversation. He gets frustrated
      easily and has a hard time being understood. He continues to confuse pronouns and
      makes some grammatical errors. He is able to follow simple directions but has a
      hard time following complex or multistep directions with accuracy. Nonverbal
      communication includes pointing to objects of interest in order to share the
      experience ("Look mom!"). He will point to identify an object and can follow a
      point across the room. He is able to use his eye contact to direct yours to
      moderate social interactions.Marcus has a special interest in Thomas the Tank
      Engine Train and Disney movies but is able to move away from those topics to
      engage in other play interests. Repetitive behaviors are not noted. Toe walking,
      hand flapping, or spinning, or unusual hand motions or observation of objects
      were not observed.Difficulties noted today include delays in his receptive and
      expressive language, poor intelligibility, dysfluency, and impaired motor
      planning. He recently underwent an audiogram which was normal. You decide to
      refer to a specialist for further evaluation.

PMID- 22472946
TI  - Comparing the effects of two different irrigation solutions on an isolated
      perfused vertebrate retina.
AB  - PURPOSE: To compare the effect of a taurine-containing intraocular irrigation
      solution (PuriProtect TM) to a standard irrigation solution (BSS TM) we evaluated
      the retinal function using an electroretinogram (ERG) and analyzed the survival
      of retinal ganglion cells on isolated whole mount retinas. MATERIALS AND METHODS:
      During ERG recordings, each irrigation solution was superfused for 45 min with
      the relevant irrigation solution. To investigate the effects on photoreceptor
      function, 1 m M asparate was added to obtain a-waves.The recovery of the a- and b
      wave was monitored after superfusing the retinas with standard medium again. To
      evaluate the percentage of dead ganglion cells, retinas were stored for 24 h at 4
      degrees C in darkness and after staining the retinas with ethidium homodimer-1
      the retinas were analyzed using fluorescence microscopy. RESULTS: The application
      of standard medium supplemented with 2 m M taurine resulted in a significant
      increase of the b-wave amplitude compared to standard medium alone. The a-wave
      amplitudes showed no significant changes under taurine supplementation. Compared
      to standard medium BSS showed no significant decrease in b-wave amplitudes, but a
      significant decrease ina-wave amplitudes. In contrast to BSS there were no
      significant changes in the a- or b-wave amplitudes detectable after the
      application of PuriProtect. At the end of the washout period no significant
      changes in a- or b-wave amplitudes were recorded for any tested irrigation
      solution. Retinas stored for 24 h in PuriProtect or in standard medium with
      taurine had a statistically significant smaller amount of dead cells than retinas
      stored in standard medium without taurine supplementation. CONCLUSIONS: BSS does
      not seem to be an ideal irrigation solution, because it compromises the a-wave in
      the ERG. In contrast to BSS, PuriProtect showed no significant impact on the ERG
      and showed a better long-term effect on ganglion cell survival. Taurine
      supplementation,therefore, seems to be neuroprotective and its supplementation to
      an intraocular irrigation solution favorable for the retina.

PMID- 22472944
TI  - Development of eating behavior:  biology and context.
AB  - Eating is necessary for survival, gives great pleasure, and can be perturbed
      leading to undernutrition, overnutrition, and eating disorders. The development
      of feeding in humans relies on complex interplay between homeostatic mechanisms;
      neural reward systems; and child motor, sensory, and socioemotional capability.
      Furthermore, parenting, social influences, and the food environment influence the
      development of eating behavior. The rapid expansion of new knowledge in this
      field, from basic science to clinical and community-based research, is expected
      to lead to urgently needed research in support of effective, evidence-based
      prevention and treatment strategies for undernutrition, overnutrition, and eating
      disorders in early childhood. Using a biopsychosocial approach, this review
      covers current knowledge of the development of eating behavior from the brain to
      the individual child, taking into account important contextual influences.

PMID- 22472947
TI  - The effects of a multifunctional oligomer and its incorporation strategies on the
      gene delivery efficiency of poly(L-lysine).
AB  - A novel multifunctional oligomer is synthesized and incorporated to enhance the
      gene delivery efficiency of PLL via non-electrostatic assembly and covalent
      grafting strategies. The improvement of the gene delivery efficiency is dependent
      on the gene carrying complex properties, and the properties are dependent on the
      oligomer incorporation strategy.

PMID- 22472948
TI  - Human erythropoietin gene delivery using an arginine-grafted bioreducible polymer
      system.
AB  - Erythropoiesis-stimulating agents are widely used to treat anemia for chronic
      kidney disease (CKD) and cancer, however, several clinical limitations impede
      their effectiveness. Nonviral gene therapy systems are a novel solution to these
      problems as they provide stable and low immunogenic protein expression levels.
      Here, we show the application of an arginine-grafted bioreducible poly(disulfide
      amine) (ABP) polymer gene delivery system as a platform for in vivo transfer of
      human erythropoietin plasmid DNA (phEPO) to produce long-term, therapeutic
      erythropoiesis. A single systemic injection of phEPO/ABP polyplex led to higher
      hematocrit levels over a 60-day period accompanied with reticulocytosis and high
      hEPO protein expression. In addition, we found that the distinct temporal and
      spatial distribution of phEPO/ABP polyplexes contributed to increased
      erythropoietic effects compared to those of traditional EPO therapies. Overall,
      our study suggests that ABP polymer-based gene therapy provides a promising
      clinical strategy to reach effective therapeutic levels of hEPO gene.

PMID- 22472949
TI  - Lentivector transduction improves outcomes over transplantation of human HSCs
      alone in NOD/SCID/Fabry mice.
AB  - Fabry disease is a lysosomal storage disorder caused by a deficiency of alpha
      galactosidase A (alpha-gal A) activity that results in progressive
      globotriaosylceramide (Gb(3)) deposition. We created a fully congenic nonobese
      diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to
      facilitate the in vivo assessment of human cell-directed therapies for Fabry
      disease. This pure line was generated after 11 generations of backcrosses and was
      found, as expected, to have a reduced immune compartment and background alpha-gal
      A activity. Next, we transplanted normal human CD34(+) cells transduced with a
      control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a
      therapeutic bicistronic LV (LV-alpha-gal A/internal ribosome entry site
      (IRES)/hCD25). While both experimental groups showed similar engraftment levels,
      only the therapeutic group displayed a significant increase in plasma alpha-gal A
      activity. Gb(3) quantification at 12 weeks revealed metabolic correction in the
      spleen, lung, and liver for both groups. Importantly, only in the therapeutically
      transduced cohort was a significant Gb(3) reduction found in the heart and
      kidney, key target organs for the amelioration of Fabry disease in humans.

PMID- 22472950
TI  - Lentiviral vector induced insertional haploinsufficiency of Ebf1 causes murine
      leukemia.
AB  - Integrating vectors developed on the basis of various retroviruses have
      demonstrated therapeutic potential following genetic modification of long-lived
      hematopoietic stem and progenitor cells. Lentiviral vectors (LV) are assumed to
      circumvent genotoxic events previously observed with gamma-retroviral vectors,
      due to their integration bias to transcription units in comparison to the gamma
      retroviral preference for promoter regions and CpG islands. However, recently
      several studies have revealed the potential for gene activation by LV insertions.
      Here, we report a murine acute B-lymphoblastic leukemia (B-ALL) triggered by
      insertional gene inactivation. LV integration occurred into the 8th intron of
      Ebf1, a major regulator of B-lymphopoiesis. Various aberrant splice variants
      could be detected that involved splice donor and acceptor sites of the lentiviral
      construct, inducing downregulation of Ebf1 full-length message. The transcriptome
      signature was compatible with loss of this major determinant of B-cell
      differentiation, with partial acquisition of myeloid markers, including Csf1r
      (macrophage colony-stimulating factor (M-CSF) receptor). This was accompanied by
      receptor phosphorylation and STAT5 activation, both most likely contributing to
      leukemic progression. Our results highlight the risk of intragenic vector
      integration to initiate leukemia by inducing haploinsufficiency of a tumor
      suppressor gene. We propose to address this risk in future vector design.

PMID- 22472951
TI  - A small-molecule-controlled system for efficient pseudotyping of prototype foamy
      virus vectors.
AB  - Foamy virus (FV) vector systems have recently demonstrated their power as
      efficient gene transfer tools for different target tissues. Unfortunately, FVs
      cannot be naturally pseudotyped by heterologous viral glycoproteins due to an
      unusual particle morphogenesis involving a FV Env-dependent particle release
      process. Therefore, current FV vector systems are constrained to the broad host
      cell range provided by the cognate viral glycoprotein. We evaluated different
      approaches for pseudotyping of FV vectors, in which the specific FV Gag-Env
      interaction, essential for particle egress, is substituted by a small-molecule
      controlled heterodimerization (HD) system. In one system developed, one HD-domain
      (HDD) is fused to a membrane-targeting domain (MTD), such as the human
      immunodeficiency virus (HIV) Gag matrix (MA) subunit, with a second fused to the
      FV capsid protein. Coexpression of both components with different heterologous
      viral glycoproteins allowed an efficient, dimerizer-dependent pseudotyping of FV
      capsids. With this system FV vesicular stomatitis virus glycoprotein (VSV-G)
      pseudotype titers greater than 1 * 10(6) IU/ml were obtained, at levels
      comparable to authentic FV vector particles. As a proof-of-principle we
      demonstrate that Pac2 cells, naturally resistant to FV vectors, become permissive
      to FV VSV-G pseudotypes. Similar to other retroviral vectors, this FV
      pseudotyping system now enables adaptation of cell-specific targeting approaches
      for FVs.

PMID- 22472952
TI  - Pityriasis lichenoides et varioliformis acuta with numerous CD30(+) cells: a
      variant mimicking lymphomatoid papulosis and other cutaneous lymphomas. A
      clinicopathologic, immunohistochemical, and molecular biological study of 13
      cases.
AB  - Pityriasis lichenoides comprises a clinicopathologic spectrum of cutaneous
      inflammatory disorders, with the 2 most common variants being pityriasis
      lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica.
      The aim of the study was to describe 13 cases of a unique PLEVA variant
      characterized in the conspicuous CD30 component and thus mimicking lymphomatoid
      papulosis (LyP), a condition currently classified in the spectrum of CD30
      lymphoproliferative disorders. The cohort included 10 female and 3 male patients
      whose ages at diagnosis ranged from 7 to 89 years (mean 41 y; median 39 y). The
      clinical manifestation was that of PLEVA, with small erythematous macules quickly
      evolving into necrotic papules. No waxing and waning was seen on follow-up in any
      of the cases. Histopathologically, typical features of PLEVA were present, but an
      unusual finding was occurrence of a considerable number of CD30 small lymphocytes
      as detected immunohistochemically. Over half of the cases also displayed a large
      number of CD8 cells and showed coexpression of CD8 and CD30 in the intraepidermal
      and dermal component of the infiltrate. Of the 11 cases of PLEVA studied for T
      cell receptor gene rearrangement, 6 evidenced a monoclonal T-cell population, and
      5 were polyclonal. Parvovirus B19 (PVB19) DNA was identified in 4 of 10 cases
      investigated, and positive serology was observed for PVB19 in 2 patients,
      altogether suggesting that PVB19 is pathogenetically linked to PLEVA at least in
      a subset of cases. The presence of CD30 lymphocytes and CD8 lymphocytes would be
      consistent with an inflammatory antiviral response, as CD30, even atypically
      appearing lymphoid cells have been identified in some viral skin diseases. The
      main significance of the PLEVA variant is, however, its potential confusion with
      LyP or some cytotoxic lymphomas. Admittedly, the CD30 PLEVA variant described
      herein and LyP show considerable overlap if one takes into account all known
      variations of the 2 conditions recognized in recent years, thus suggesting that
      LyP and PLEVA may be much more biologically closely related entities than
      currently thought or can even occur on a clinicopathologic spectrum.

PMID- 22472953
TI  - Is there a spectrum of cytologic atypia in type a thymomas analogous to that seen
      in type B thymomas? A pilot study of 13 cases.
AB  - Thirteen cases of type A thymoma are reported showing the characteristic
      architectural attributes of this tumor type (World Health Organization), such as
      lobulation, perivascular spaces, gland-like formations, and cystic changes, but
      also displaying atypical features, as defined by increased mitotic activity, mild
      to moderate nuclear atypia, and/or scattered small foci of necrosis. The tumors
      were similar to type B3 thymomas in many respects, except for the fact that the
      tumor cells were spindled instead of round/polygonal. The existence of these
      cases suggests the desirability of an expansion of the type A thymoma category,
      analogous to that currently used for type B tumors. The various nomenclature
      options that could be used to name these tumors have been discussed.

PMID- 22472954
TI  - The differential expression of PAX2 and PAX8 in the ovarian surface epithelium
      and fallopian tubal epithelium is an important issue.

PMID- 22472955
TI  - Multiple dysplastic liver nodules in PFIC2 underscore risk for neoplasia
      associated with functional BSEP deficiency.

PMID- 22472957
TI  - Gastric adenocarcinoma with chief cell differentiation: a proposal for
      reclassification as oxyntic gland polyp/adenoma.
AB  - Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been reported
      as a new, rare variant of gastric adenocarcinoma. Only 12 cases in Japanese
      patients have been described to date, but they demonstrate distinct
      clinicopathologic features. To further characterize these lesions, we have
      collected 10 additional cases. Patients ranged in age from 44 to 79 years (mean,
      64.2 y) with a relatively equal sex distribution (6 women and 4 men). Stratified
      by race, 4 patients were Hispanic, 2 were White, 2 were African American, 1 was
      Asian (Chinese), and the race was unknown for 1 patient. All patients presented
      with gastroesophageal reflux that prompted an endoscopic examination. The
      majority of GA-CCDs were identified in the fundus (7 of 10, 70%) and the
      remaining in the cardia (n=3). Grossly, they were solitary and polypoid, ranging
      in size from 0.2 to 0.8 cm (mean, 0.4 cm). Histologically, all cases were
      centered in the deep mucosa, with focal involvement of surface foveolar
      epithelium in 3 (30%) cases but not the submucosa. The tumors consisted of
      clustered glands and irregular branching cords of oxyntic epithelium. Thin wisps
      of radiating smooth muscle separated the epithelium, but desmoplasia was
      distinctly absent in all cases. The oxyntic mucosa was 1 to 2 cells thick and
      composed of a mixture of mucous neck, parietal, and chief cells. In 7 of 10 (70%)
      cases, chief cells were the predominant cell type, whereas the remaining 3 cases
      consisted primarily of mucous neck cells. The nuclei were mildly enlarged with
      slight nuclear pleomorphism, but no mitotic figures were identified. In addition,
      necrosis, lymphovascular invasion, and perineural invasion were absent.
      Immunohistochemically, GA-CCDs were diffusely positive for MUC6 (10 of 10, 100%)
      and negative for MUC5AC (0%) and MUC2 (0%). Ki-67 immunolabeling demonstrated
      variable expression, with the highest areas ranging from 0.2% to 10%. Clinical
      follow-up was available for 9 of 10 (90%) patients and ranged from 6 to 39
      months. One patient had persistence of lesion at 6 months because of incomplete
      removal, whereas the other 8 were disease free. In summary, GA-CCDs are solitary,
      mucosal lesions of the gastric cardia/fundus that arise in patients from multiple
      ethnic backgrounds. Considering that patients within this study and those
      reported previously have had neither true recurrence nor progression of disease,
      these lesions are best regarded as benign. Consequently, the term GA-CCD is
      contradictory and we prefer the descriptive term "oxyntic gland polyp/adenoma"
      until further studies can clarify the pathogenesis of these lesions and their
      natural history.

PMID- 22472958
TI  - Microscopic diffuse large B-cell lymphoma (DLBCL) occurring in pseudocysts: do
      these tumors belong to the category of DLBCL associated with chronic
      inflammation?
AB  - We report 2 cases of localized, microscopic diffuse large B-cell lymphoma (DLBCL)
      that were detected incidentally within pseudocysts. In case 1, the neoplasm was
      identified within a 26-cm, 860-g adrenal gland pseudocyst. In case 2, the
      neoplasm was detected within a 9-cm, 90-g paratesticular pseudocyst. In both
      cases, the neoplastic cells were large, had a nongerminal center B-cell
      immunophenotype, and were positive for Epstein-Barr virus (EBV)-encoded RNA
      detected by in situ hybridization. The most appropriate classification of these
      tumors using current World Health Organization classification is uncertain. The
      best fit seems to be DLBCL associated with chronic inflammation (DLBCL-CI),
      defined as DLBCL arising in the context of long-standing chronic inflammation and
      associated with EBV infection, with the prototype for this category being
      pyothorax-associated lymphoma. This term has been used by others in the
      literature for tumors similar to the cases reported here. However, in the 2 cases
      we report chronic inflammation was not a prominent feature, and the inflammatory
      cells that were present showed little relationship to the lymphoma cells. The
      findings in these cases have led us to question the role of chronic inflammation
      in pathogenesis. Perhaps the closed space of the pseudocyst, by preventing a
      cytolytic response to EBV-infected cells, results in local immunodeficiency that
      may be most important for pathogenesis. We also have concerns about using the
      term DLBCL-CI for these tumors. Perhaps the cases we report and the few other
      similar cases reported previously deserve their own category in a future version
      of the World Health Organization classification.

PMID- 22472959
TI  - Cutaneous and subcutaneous pleomorphic liposarcoma: a clinicopathologic study of
      29 cases with evaluation of MDM2 gene amplification in 26.
AB  - Pleomorphic liposarcoma (PL) is an uncommon form of liposarcoma that rarely
      occurs in the skin and subcutis. As its behavior in this setting is incompletely
      characterized, we undertook a study of a series of superficial PLs, defined as
      those arising or based primarily in the dermis and/or subcutis without
      involvement of deep structures. In addition, MDM2 gene amplification, a
      diagnostic signature of well-differentiated/dedifferentiated liposarcoma
      (WDL/DL), was evaluated to address the recent observation that this gene is
      amplified within PL-like areas in DL. PLs were obtained from institutional and
      consultation files (n=29). Cases were evaluated with respect to age, sex,
      location (dermis, dermis and subcutis, subcutis), size, predominant pattern
      (pleomorphic spindled or epithelioid), extent of lipogenic differentiation, and
      tumor necrosis. MDM2 amplification was analyzed using FISH on formalin-fixed,
      paraffin-embedded material in 26 cases. Patients ranged in age from 5 to 93 years
      (M:F=1.4:1). Tumors were located on the extremity (n=15), trunk (n=7), and head
      and neck (n=7) and involved the dermis (n=4), dermis and subcutis (n=10), and
      subcutis (n=15). Tumor size ranged from 0.8 to 15 cm (median=2 cm). All were
      mitotically active high-grade sarcomas [FNCLCC grade 2 (n=23) or 3 (n=6)] with
      either a pleomorphic spindled (n=24) or an epithelioid pattern (n=5) with
      variable extent of lipogenic differentiation [<25% (n=15), 25% to 50% (n=9), >50%
      (n=5)]. Necrosis was present in 3 cases. MDM2 gene amplification was present in 3
      of 26 cases. Follow-up information in 24 cases (range=1 to 192 mo; median=48 mo;
      mean=59 mo) revealed local recurrences (4/24) but no metastasis or death from
      disease. We conclude that cutaneous and subcutaneous PLs, despite their high
      grade, have a much more favorable outcome compared with their deep-seated
      counterparts, most likely attributed to their small size and superficial
      location. The low incidence of MDM2 gene amplification in our series indicates
      that most superficial PLs are unrelated to WDL/DL. PL likely evolves by way of
      more than 1 molecular pathway.

PMID- 22472961
TI  - Pseudo helix-sense-selective polymerisation of achiral substituted acetylenes.
AB  - Pseudo helix-sense-selective polymerisation of a wide range of achiral
      substituted acetylenes having dynamic covalent bonds has been realised to yield
      static one-handed helical polymers without any other chiral moieties.

PMID- 22472960
TI  - Paradoxical relationship between the degree of EGFR amplification and outcome in
      glioblastomas.
AB  - Glioblastoma (GBM) is the most common primary brain tumor in adults and often has
      amplification of the epidermal growth factor receptor (EGFR) gene. The value of
      EGFR as a prognostic marker in GBMs is unclear; some studies have shown an
      adverse correlation, whereas others have indicated a neutral or even favorable
      association with longer survival. Furthermore, EGFR-amplified GBMs are usually
      regarded as a single subgroup of tumors, although the range of EGFR copy number
      varies greatly. In this study, 532 GBMs were analyzed for EGFR amplification via
      fluorescence in situ hybridization at the time of initial diagnosis. Although
      there was no difference in survival by EGFR amplification (P = 0.33),
      stratification by the amount of EGFR amplification showed that, surprisingly,
      median survival was 39% longer in the high-amplifier group (EGFR:chromosome 7
      ratio >20) compared to nonamplified GBMs (P = 0.03) and was 43% longer compared
      to GBMs with low to moderate EGFR amplification (EGFR:chromosome 7 ratio = 2 to
      20; P = 0.0007). Stratifying by postsurgical treatment regimens, this difference
      was seen only when temozolomide (TMZ) was used; tumors without amplification and
      with high EGFR amplification both responded better to TMZ than those with low to
      moderate amplification (P = 0.01), whereas GBMs that had not been treated with
      adjuvant therapy nor with adjuvant therapy lacking TMZ showed no survival
      differences (P = 0.63 and 0.91, respectively). These results suggest that GBMs
      with EGFR amplification are a heterogenous group of tumors and that behavior
      might differ according to the degree of amplification, although not in a
      straightforward dose-response manner.

PMID- 22472962
TI  - Cancer and longevity--is there a trade-off? A study of cooccurrence in Danish
      twin pairs born 1900-1918.
AB  - BACKGROUND: Animal models and a few human studies have suggested a complex
      interaction between cancer risk and longevity indicating a trade-off where low
      cancer risk is associated with accelerating aging phenotypes and, vice versa,
      that longevity potential comes with the cost of increased cancer risk. This
      hypothesis predicts that longevity in one twin is associated with increased
      cancer risk in the cotwin. METHODS: A total of 4,354 twin pairs born 1900-1918 in
      Denmark were followed for mortality in the Danish Civil Registration System
      through 2008 and for cancer incidence in the period 1943-2008 through the Danish
      Cancer Registry. RESULTS: The 8,139 twins who provided risk time for cancer
      occurrence entered the study between ages 24 and 43 (mean 33 years), and each
      participant was followed up to death, emigration, or at least 90 years of age.
      The total follow-up time was 353,410 person-years and, 2,524 cancers were
      diagnosed. A negative association between age at death of a twin and cancer
      incidence in the cotwin was found in the overall analyses as well as in the
      subanalysis stratified on sex, zygosity, and random selection of one twin from
      each twin pair. CONCLUSIONS: This study did not find evidence of a cancer
      longevity trade-off in humans. On the contrary, it suggested that longevity in
      one twin is associated with lower cancer incidence in the cotwin, indicating
      familial factors associated with both low cancer occurrence and longevity.

PMID- 22472963
TI  - Validation of the Cannabis Abuse Screening Test in a sample of cannabis
      inpatients.
AB  - The present study aims at validating the Cannabis Abuse Screening Test (CAST) in
      a clinical sample of adolescent and young adult cannabis users seeking treatment.
      Applying a classical test theory approach using DSM-IV diagnoses as gold
      standard, two versions of the CAST questionnaire are compared. The sample
      consisted of 140 subjects aged 15-26 years (mean 18.9) recruited from two
      cannabis treatment centers. Gold standard diagnoses were assessed using the
      Adolescent Diagnostic Interview-Light. Internal structure and consistency of the
      CAST were assessed by principal component analysis and Cronbach's alpha. Optimal
      thresholds were defined using receiver operating characteristic analysis. Both
      the binary and the full test version revealed unidimensional structures with
      moderate to satisfactory internal consistency (alpha = 0.66 and 0.73). Screening
      properties were unsatisfactory when the CAST was compared against cannabis
      dependence. With regard to cannabis use disorders, both test versions yielded
      comparable and good sensitivity and specificity at cut-off 3 (binary: 92.2%,
      66.7%) and 6 (full: 93.0%, 66.7%). Overall, the full CAST may be used for
      screening cannabis use disorders in clinical settings. Further research may use
      validation methods that do without gold standard.

PMID- 22472964
TI  - Conversion of sensory signals into perceptual decisions.
AB  - A fundamental problem in neurobiology is to understand how brain circuits
      represent sensory information and how such representations give rise to
      perception, memory and decision-making. We demonstrate that a sensory stimulus
      engages multiple areas of the cerebral cortex, including primary sensory,
      prefrontal, premotor and motor cortices. As information transverses the cortical
      circuits it shows progressively more relation to perception, memory and decision
      reports. In particular, we show how somatosensory areas on the parietal lobe
      generate a parameterized representation of a tactile stimulus. This
      representation is maintained in working memory by prefrontal and premotor areas
      of the frontal lobe. The presentation of a second stimulus, that monkeys are
      trained to compare with the first, generates decision-related activity reflecting
      which stimulus had the higher frequency. Importantly, decision-related activity
      is observed across several cortical circuits including prefrontal, premotor and
      parietal cortices. Sensory information is encoded by neuronal populations with
      opposite tuning, and suggests that a simple subtraction operation could be the
      underlying mechanism by which past and present sensory information is compared to
      generate perceptual decisions.

PMID- 22472965
TI  - Coumarin-derived transformable fluorescent sensor for Zn2+.
AB  - We report a coumarin-derived fluorescent sensor for Zn(2+) termed CTS. CTS shows
      excellent binding selectivity for Zn(2+) over competing metal ions due to the
      transformable ability of CTS, that is the displacement of other metal ions by
      Zn(2+), which induces transformation of chelation from an amide to an imidic acid
      tautomeric form.

PMID- 22472966
TI  - Comparison of the usefulness of hydatid cyst fluid, native antigen B and
      recombinant antigen B8/1 for serological diagnosis of cystic echinococcosis.
AB  - For serodiagnosis of cystic echinococcosis (CE), the usefulness of three native
      antigens, a hydatid cyst fluid (HCF) obtained from infected sheep in China, two
      types of antigen B prepared from each HCF obtained in Iran and China, and one
      recombinant antigen B8/1 (RAgB), were evaluated by ELISA using a total of 155
      serum samples from Iran, Turkey, China and Japan. Both the Iranian native antigen
      B and RAgB had high sensitivity, but RAgB showed an excellent specificity in
      comparison with native antigens because none of the serum samples of healthy
      people from Iran and Japan became positive with this antigen except one case of
      taeniasis. The taeniasis case exceptionally showing cross reactivity with all
      antigens was considered to be co-infected with Echinococcus granulosus and Taenia
      saginata. The recombinant antigen showing a high diagnostic odds ratio in
      comparison with other evaluated antigens might be recommended for diagnosis of CE
      in different CE-endemic areas.

PMID- 22472967
TI  - Non-invasive mechanical ventilation in hematology patients with hypoxemic acute
      respiratory failure: a false belief?

PMID- 22472970
TI  - Contemporary Modeling of Gene * Environment Effects in Randomized Multivariate
      Longitudinal Studies.
AB  - There is a great deal of interest in the analysis of Genotype * Environment
      interactions (G*E). There are some limitations in the typical models for the
      analysis of G*E, including well-known statistical problems in identifying
      interactions and unobserved heterogeneity of persons across groups. The impact of
      a treatment may depend on the level of an unobserved variable, and this variation
      may dampen the estimated impact of treatment. Some researchers have noted that
      genetic variation may sometimes account for unobserved, and hence unaccounted
      for, heterogeneity. The statistical power associated with the G*E design has been
      studied in many different ways, and most results show that the small effects
      expected require relatively large or nonrepresentative samples (i.e., extreme
      groups). In this article, we describe some alternative approaches, such as
      randomized designs with multiple measures, multiple groups, multiple occasions,
      and analyses, to identify latent (unobserved) classes of people. These approaches
      are illustrated with data from the Aging, Demographics, and Memory Study (part of
      the Health and Retirement Study) examining the relations among episodic memory
      (based on word recall), APOE4 genotype, and educational attainment (as a proxy
      for an environmental exposure). Randomized clinical trials (RCTs) and randomized
      field trials (RFTs) have multiple strengths in the estimation of causal
      influences, and we discuss how measured genotypes can be incorporated into these
      designs. Use of these contemporary modeling techniques often requires different
      kinds of data be collected and encourages the formation of parsimonious models
      with fewer overall parameters, allowing specific G*E hypotheses to be
      investigated with a reasonable statistical foundation. 

PMID- 22472971
TI  - BDNF expression in olfactory bulb and epithelium during regeneration of olfactory
      epithelium.
AB  - To further understand the roles of growth factors in the olfactory neurogenesis,
      we studied the mRNA levels of diverse genes in olfactory bulb (OB) and olfactory
      epithelium (OE) during the regeneration process of OE. mRNA expression levels of
      various genes in the OB and OE during the regeneration processes of OE from
      damage induced by methimazole administration were studied by DNA microarray
      analysis. The results were confirmed by quantitative real-time RT-PCR and
      immunohistochemistry. Expression levels of various genes dramatically changed
      during the observation period. Among them, mRNA expression of BDNF dramatically
      increased in OE during the first 7 days and then decreased. In contrast, mRNA
      expression of BDNF in OB significantly decreased during the first 7 days after
      administration and then gradually increased. The changes in the mRNA levels of
      OMP in OB precisely followed those of OMP in OE and OB. The present results
      suggest that BDNF in OE contributes to the early stage of regeneration, and BDNF
      in OB has its role in the late stage of regeneration of olfactory receptor
      neurons (ORNs).

PMID- 22472972
TI  - Human biology of weight maintenance after weight loss.
AB  - One year after losing weight, most people have regained a significant part of the
      lost weight. As such, weight regain after weight loss has a negative impact on
      human health. The risk for weight regain is determined by psychosocial and
      behavioral factors as well as by various physiological and molecular parameters.
      Here, the latter intrinsic factors are reviewed and assembled into four
      functional modules, two related to the energy balance and two related to
      resistance against weight loss. Reported genetic factors do not reveal additional
      functional processes. The modules form nodes in a network describing the complex
      interactions of intrinsically determined weight maintenance. This network
      indicates that after an initial weight loss persons with a high baseline fat mass
      will most easily succeed in maintaining weight, because they can lose fat without
      raising stress in adipocytes and at the same time spare fat-free mass. However,
      continued weight loss and weight maintenance requires extra measures like
      increased physical activity, limited energy intake and a fat-free sparing
      composition of the diet. Eventually, this network may help to design novel
      therapeutic measures based on preventing the return effect of specific plasma
      factors or by preventing the accumulation of adipocyte cellular stress.

PMID- 22472973
TI  - Effect of ischemia duration on autoantibody response in rats undergoing retinal
      ischemia-reperfusion.
AB  - Both the innate and the adaptive immune systems are involved in the pathogenic
      processes following ischemia-reperfusion injury. We analyzed the possible
      correlation between the duration of ischemia and autoantibody diversification in
      a model of ocular ischemia. Rats were subjected to 30, 45, or 90 min of ischemia,
      and retinal ganglion cell (RGC) density and antibody reactivity were analyzed via
      customized protein microarray slides. After ocular ischemia, significant
      alterations in antibody response were observed, while increasing exposure caused
      more severe RGC damage. Distinct antibody responses after ischemia were detected;
      these alterations comprised decreased reactivities against cyclophilin A and
      glyceraldehyde-3-phosphate dehydrogenase, possibly due to increased binding of
      circulating antibodies to debris material. Other antibodies, like those against
      alpha(5)beta(1)-integrin or beta(2) -adrenergic receptor, were upregulated after
      ischemia.

PMID- 22472974
TI  - Seeing eye to eye with gene therapy.

PMID- 22472977
TI  - A water-soluble coelenterazine for sensitive in vivo imaging of coelenterate
      luciferases.

PMID- 22472978
TI  - mRNA leapfrogs DNA to show promise for therapeutic gene transfer.

PMID- 22472979
TI  - Do cell-penetrating peptides actually "penetrate" cellular membranes?

PMID- 22472980
TI  - Progress in the development of hepatitis C virus vaccines.

PMID- 22472981
TI  - Sleep-wake disturbances in Parkinson's disease: current evidence regarding
      diagnostic and therapeutic decisions.
AB  - Sleep disorders have been frequently reported in patients with Parkinson's
      disease (PD). However, there is insufficient evidence to guide precise
      recommendations on some diagnostic and treatment strategies. Here, we review
      clinical studies dealing with sleep abnormalities in PD and present clinical
      recommendations. Previous studies describing insomnia, excessive daytime
      sleepiness, narcolepsy-like episodes, circadian changes, sleep-disordered
      breathing, rapid eye movement sleep behavior disorder, vivid dreams and restless
      legs syndrome are evaluated. Longitudinal studies associating sleep disorders
      with PD onset or clinical deterioration are rare: only one longitudinal study
      associated daytime sleepiness with PD onset. Evidence suggests that clinical
      investigations must include direct questioning about depressive symptoms,
      nocturnal cramps, pain, nocturia and nighttime off periods. A patient interview
      must be conducted regarding sleep symptoms, including nightmares, abnormal
      behavior during sleep, snoring, restless legs syndrome and daytime sleepiness.
      Initial evidence indicates that light therapy improves motor function and
      depression. Advice on sleep hygiene, the treatment of concomitant depression and
      the careful use of dopaminergic drugs and hypnosedative agents should be
      considered. To date, very few controlled studies are available to make a
      recommendation for the management of sleep-wake disturbances in PD.

PMID- 22472982
TI  - Shape-controlled tunable homochromatic luminescence and inner photoelectric
      effect of hexagonal Na1.23Ca0.12Y1.28Er0.24F6 phosphors.
AB  - Novel hexagonal Na1.23Ca0.12Y1.28Er0.24F6 nanodisks, microtubes, and nanorods
      were synthesized hydrothermally for the first time. Time-dependent morphology
      evolution showed that the resulting nanodisks, microtubes, and nanorods were
      synthesized by a dissolution-reconstruction formation mechanism. With the help of
      a 980 nm semiconductor laser, tunable homochromatic luminescence was observed by
      exciting single hexagonal Na1.23Ca0.12Y1.28Er0.24F6 nanodisks, microtubes, and
      nanorods, respectively. Simultaneously, the inner photoelectric effect was
      witnessed in the hexagonal Na1.23Ca0.12Y1.28Er0.24F6 nanodisks, microtubes, and
      nanorods under 980 nm excitation. We attributed anomalous inner photoelectric
      current to the presence of a laser stepped resonant excitation energy migration
      in the Na1.23Ca0.12Y1.28Er0.24F6 matrix when a laser was applied to it.
      Simultaneous control of homochromatic luminescence and inner photoelectric effect
      were achieved by modifying morphological shapes of single
      Na1.23Ca0.12Y1.28Er0.24F6 phosphors. 

PMID- 22472983
TI  - Monitoring the safety of medicines used off-label.
AB  - Off-label use of medicines is common. Because many off-label uses have not been
      carefully studied, it is important that postmarketing drug safety systems be able
      to identify, assess, and monitor adverse events that occur in the off-label
      setting. The full range of postmarketing surveillance and analysis tools can be
      utilized to study the adverse effects of medicines used off-label.

PMID- 22472984
TI  - Off-label drug use in pediatric patients.

PMID- 22472985
TI  - The use of observational health-care data to identify and report on off-label use
      of biopharmaceutical products.
AB  - Significant efforts are under way to develop analytic surveillance systems that
      can leverage observational health-care data to monitor biopharmaceutical
      products. The systems are being designed to identify safety-related events in a
      post-approval setting, when the products are already on the market.An additional
      application of such a system would be the use of observational data to help
      identify and track off-label use of marketed biopharmaceutical products in
      specific populations.The opportunities and challenges associated with such a
      system, as well as the underlying data sources themselves, are reviewed in this
      article.

PMID- 22472986
TI  - Effects of ritonavir-boosted lopinavir on the pharmacokinetics of quinine.
AB  - The centuries-old antimalarial drug, quinine, continues to play a critical role
      in the treatment of severe falciparum malaria and uncomplicated malaria in
      pregnant women. It shares cytochrome P450 (CYP )-mediated metabolic pathways with
      several commonly used antiretroviral drugs, raising the potential for clinically
      important drug-drug interactions. A phase I pharmacokinetic study was conducted
      to assess the impact of long-term use of ritonavir-boosted lopinavir (LPV/r) on
      quinine pharmacokinetics in healthy volunteers. LP V/r significantly decreased
      the exposure of quinine and its major active metabolite, 3-hydroxyquinine, in
      both total and free (unbound) forms. These findings highlight the complex nature
      of the influence exerted by LPV/r on several of the drug-metabolizing enzymes
      involved in quinine disposition,including CYP 3A4, UDP-glucuronosyltransferase
      (UG T), and P-glycoprotein (P-gp). A decline in quinine exposure may compromise
      clinical efficacy. Further studies are warranted to assess changes in quinine
      pharmacokinetics and treatment outcomes in patients with acute malaria receiving
      antiretroviral therapy that includes LPV/r.

PMID- 22472987
TI  - Interpatient pharmacokinetic and pharmacodynamic variability of carrier-mediated
      anticancer agents.
AB  - Major advances in the field of carrier-mediated agents (CMAs) have revolutionized
      drug delivery capabilities over the past decade. While providing numerous
      advantages over their small-molecule counterparts (solubility,duration of
      exposure, and delivery to the site of action are higher), these agents display
      substantial variability in systemic clearance (CL) and distribution, tumor
      delivery, and pharmacologic effects. This review provides an overview of factors
      that affect the pharmacokinetics (PK) and pharmacodynamics (PD) of CMAs in
      preclinical models and patients.

PMID- 22472988
TI  - Electronic health records: the new vehicle for drug labeling, safety, and
      efficacy.
AB  - As labeling has become more complex, effective provider communication has become
      more difficult. Until the HITECH (Health Information Technology for Economic and
      Clinical Health) Act, which provided billions of federal payments to encourage
      the use of electronic health records (EHRs) and e-prescribing, adoption of EHRs
      was slow. Delivery of actionable drug information within EHRs unites providers,
      patients,professional liability carriers, and the US Food and Drug Administration
      (FDA) because it improves safety and decreases liability/costs. At PDR Network,
      we deliver full labeling, warnings,risk evaluation and mitigation strategies
      (REMS), adverse event reporting, and adherence services within the provider's
      workflow, across multiple EHRs.

PMID- 22472989
TI  - Joint modeling of efficacy, dropout, and tolerability in flexible-dose trials: a
      case study in depression.
AB  - Many difficulties may arise during the modeling of the time course of Hamilton
      Rating Scale for Depression (HAM D)scores in clinical trials for the evaluation
      of antidepressant drugs: (i) flexible designs, used to increase the chance of
      selecting more efficacious doses, (ii) dropout events, and (iii) adverse effects
      related to the experimental compound.It is crucial to take into account all these
      factors when designing an appropriate model of the HAM D time course and to
      obtain a realistic description of the dropout process. In this work, we propose
      an integrated approach to the modeling of a double-blind, flexible-dose, placebo
      controlled, phase II depression trial that comprises response,tolerability, and
      dropout. We investigate three different dropout mechanisms in terms of
      informativeness. Goodness of fit is quantitatively assessed with respect to
      response (HAM D score) and dropout data. We show that dropout is a complex
      phenomenon that may be influenced by HAM D evolution, dose changes, and
      occurrence of drug-related adverse effects.

PMID- 22472990
TI  - Off-label use of drugs and medical devices: a review of policy implications.

PMID- 22472991
TI  - Impact of safety-related regulatory action on drug use in ambulatory care in the
      Netherlands.
AB  - The effect of Direct Healthcare Professional Communications (DHPCs) informing
      health-care providers of serious drug safety issues has been questioned. The aim
      of this study was to evaluate the impact of DHPCs on drug use.Nationwide
      dispensing data for the period 2000-2008 for new users of 46 drugs with one or
      more DHPCs were assessed. Impact on short-term volume of use was evaluated with
      regression models, and the presence of long-term changes in use was evaluated
      with interrupted time series analyses incorporating preexisting trends. The short
      term prescription level was lower post-DHPC in 28 (48.3%) of 58 cases. Twenty
      (34.5%) DHPCs resulted in long-term changes in use. A long-term mean reduction in
      use was observed in 26.7% of cases (95% confidence interval, -15.2 to 
      38.2%).Long-term changes in use were not significantly related to preexisting
      trends in use. Although short- and long-term decreases in use were observed after
      only half and a third of DHPCs, respectively, the decrease was substantial.

PMID- 22472993
TI  - Regulatory experience with physiologically based pharmacokinetic modeling for
      pediatric drug trials.
AB  - Physiologically based pharmacokinetic (PBPK) approaches that incorporate the
      developmental physiology and ontogeny of cytochrome P450 (CYP) enzymes may have
      value in the design of pediatric trials. Four recent submissions to the US Food
      and Drug Administration (FDA) incorporated different PBPK applications to
      pediatric drug development.Further testing of PBPK models for three drugs showed
      that these models generally under predicted drug clearance. PBPK modeling may
      have potential for improving pediatric trials through the learn-and-confirm
      approaches utilized in current regulatory submissions.

PMID- 22472992
TI  - Pharmacokinetic and pharmacodynamic variability of fluindione in octogenarians.
AB  - In the PREPA observational study, we investigated the factors influencing
      pharmacokinetic and pharmacodynamic variability in the responses to fluindione,
      an oral anticoagulant drug, in a general population of octogenarian
      inpatients.Measurements of fluindione concentrations and international normalized
      ratio (INR ) were obtained for 131 inpatients in whom fluindione treatment was
      initiated. Treatment was adjusted according to routine clinical practice. The
      data were analyzed using nonlinear mixed-effects modeling, and the parameters
      were estimated using MONOLI X 3.2. The pharmacokinetics (PK) of fluindione was
      monocompartmental, whereas the evolution of INR was modeled in accordance with a
      turnover model (inhibition of vitamin K recycling). Interindividual variability
      (II V) was very large. Clearance decreased with age and with prior administration
      of cordarone. Patients who had undergone surgery before the study had lower IC50
      values, leading to an increased sensitivity to fluindione. Pharmacokinetic
      exposure is substantially increased in elderly patients, warranting a lower dose
      of fluindione.

PMID- 22472994
TI  - Gemfibrozil is a strong inactivator of CYP2C8 in very small multiple doses.
AB  - Therapeutic doses of gemfibrozil cause mechanism-based inactivation of CYP2C8 via
      formation of gemfibrozil 1-O-beta-glucuronide. We investigated the extent of
      CYP2C8 inactivation caused by three different doses of gemfibrozil twice dailyfor
      5 days, using repaglinide as a probe drug, in 10 healthy volunteers. At the end
      of this 5-day regimen, there were dose-dependent increases in the area under the
      plasma concentration-time curve from 0 to infinity (AUC0-infinity) of repaglinide
      by3.4-, 5.5-, and 7.0-fold corresponding to 30, 100, and 600 mg of gemfibrozil,
      respectively, as compared with the control phase (P < 0.001). On the basis of a
      mechanism-based inactivation model involving gemfibrozil 1-O-beta-glucuronide, a
      gemfibrozil dose of 30 mg twice daily was estimated to inhibit CYP2C8 by >70% and
      100 mg twice daily was estimated to inhibit it by >90%. Hence, gemfibrozil is a
      strong inactivator of CYP2C8 even in very small, subtherapeutic, multiple doses.
      Administration of small gemfibrozil doses may be useful in optimizing the
      pharmacokinetics of CYP2C8 substrate drugs and in reducing the formation of their
      potentially toxic metabolites via CYP2C8.

PMID- 22472995
TI  - Safety and pharmacokinetics of escalating daily doses of the antituberculosis
      drug rifapentine in healthy volunteers.
AB  - Rifapentine (RP T) is an antituberculosis drug that may shorten treatment
      duration when substituted for rifampin (RI F).The maximal tolerated daily dose of
      RP T and its potential for cytochrome 3A4 induction and autoinduction at
      clinically relevant doses are unknown. In this phase I, dose-escalation study
      among healthy volunteers, daily doses as high asa prespecified maximum of 20
      mg/kg/day were well tolerated. Steady-state RP T concentrations increased with
      dose from 5 to 15 mg/kg, but area under the plasma concentration-time curve (AU
      C0-24) and maximum concentration (Cmax)were similar in the 15- and 20-mg/kg
      cohorts. Although RP T pharmacokinetics (PK) appeared to be time
      dependent,accumulation occurred with daily dosing. The mean AU C0-12 of oral
      midazolam (MDZ), a cytochrome 3A (CYP 3A) probe drug, was reduced by 93% with the
      coadministration of RPT and by 74% with the coadministration of RIF (P <
      0.01).Changes in the oral clearance of MDZ did not vary by RP T dose. In
      conclusion, RP T was tolerated at doses as high as20 mg/kg/day, its PK were less
      than dose-proportional, and its CYP 3A induction was robust.

PMID- 22472997
TI  - Radiation dose features and solid cancer induction in pediatric computed
      tomography.
AB  - Over the past two decades technical advances and improvements have made computed
      tomography (CT) a valuable and essential tool in the array of diagnostic imaging
      modalities. CT uses ionizing radiation (X-rays) which may damage DNA and increase
      the risk of carcinogenesis. This is especially pertinent in pediatric CT as
      children are more radiosensitive and have a longer life expectancy than adults.
      The purpose of this paper is to review and elucidate the potential harmful
      effects of ionizing radiation in terms of solid cancer induction from pediatric
      CT scanning. In the light of scientific and technical developments, we will also
      discuss the possible strategies and ongoing efforts to reduce CT radiation
      exposure in pediatric patients. In this context, we will not ignore the fact that
      a well-justified CT scan may exceed its risk and have a favorable impact.

PMID- 22472998
TI  - The risk of fracture in incident multiple sclerosis patients: the Danish National
      Health Registers.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) may be at increased risk of
      fractures owing to osteoporosis and falling. OBJECTIVE: To evaluate the risk of
      fracture in incident MS patients drawn from a dedicated MS registry compared with
      population-based controls. METHODS: We conducted a population-based cohort study
      (1996-2007) utilising the Danish National Health Registers that were linked to
      the Danish MS Registry and the Danish MS Treatment Registry. Incident MS patients
      (2963 cases) were 1:6 matched by year of birth, gender, calendar time and region
      to persons without MS (controls). Cox proportional hazards models and logistic
      regression were used to estimate the risk of fracture in MS. Time-dependent
      adjustments were made for age, history of diseases and drug use. RESULTS:
      Compared with controls, patients with MS had no overall increased risk of
      fracture (adjusted hazard ratio (adj. HR): 1.0, 95% CI: 0.9-1.2). However, the
      risk of femur/hip fracture (adj. HR: 1.9, 95% CI: 1.1-3.4) was significantly
      increased compared to controls. As compared with unexposed patients, MS patients
      who had been exposed to a short course of methylprednisolone in the prior year
      had no significantly increased risk of osteoporotic fracture (adj. HR: 1.2, 95%
      CI: 0.5-2.9). Disabled MS patients with Expanded Disability Status Scale [EDSS]
      scores between 6 and 10, had a 2.6-fold increased risk of osteoporotic fracture
      (adjusted odds ratio (adj. OR): 2.6, 95% CI: 1.0-6.6) compared to patients with
      an EDSS score between 0 and 3. CONCLUSION: Patients with MS had a higher risk of
      femur/hip fracture than controls. Disability status is probably more important
      than glucocorticoid use in the aetiology of MS and osteoporotic fracture.

PMID- 22472999
TI  - Normal human melanocytes exposed to chronic insulin and glucose supplementation
      undergo oncogenic changes and methyl group metabolism cellular redistribution.
AB  - Recent epidemiological studies have suggested a link between cancer and
      pathophysiological conditions associated with hyperinsulinemia. In this report,
      we address the possible role of insulin exposure in melanocyte transformation. To
      this aim, normal melanocytes were exposed to chronic insulin and glucose
      supplementation (twice the standard medium concentration) for at least 3 wk.
      After 3-wk treatment, melanocytes increased proliferation (doubling time: 2.7 vs.
      5.6 days, P < 0.01). After 3-wk treatment or after 3-wk treatment followed by 4
      wk reculture in standard medium, melanocytes were able to grow in soft agar
      colonies. Treated melanocytes had increased DNA content (+8%, P < 0.05),
      chromosomal aberrations, and modified oncoprotein profile: p-Akt expression
      increased (+32%, P < 0.01), Akt decreased, and c-Myc increased (+40%, P < 0.05).
      PP2A protein expression increased (+42, P < 0.05), while PP2A methylation
      decreased (-42%, P < 0.05), and PP2A activity was reduced (-27%, P < 0.05). PP2A
      transcription level was increased (ppp2r1a, PP2A subunit A, +44%, P < 0.05).
      Also, transcriptomic data revealed modifications in insr (insulin receptors,
      +10%, P < 0.05) and Il8 (inflammation protein, +99%, P < 0.01). Glycolysis was
      modified with increased transcription of Pgk1 and Hif1a (P < 0.05), decreased
      transcription of Pfkfb3 (P < 0.05), decreased activity of pyruvate kinase (P <
      0.01), and decreased pyruvate cell content as assessed by (1)H-NMR spectroscopy.
      In addition, methyl group metabolism was altered with decreased global DNA
      methylation (-51%, P < 0.01), increased cytosolic protein methylation (+18%, P <
      0.05), and consistent changes in methylated species on (1)H-NMR spectra. In
      conclusion, exposure to chronic insulin and glucose supplementation induces
      oncogenic changes and methyl group metabolism redistribution, which may be a
      biomarker of transformation.

PMID- 22473002
TI  - Refined staging for chorioretinopathy in long-chain 3-hydroxyacyl coenzyme A
      dehydrogenase deficiency.
AB  - OBJECTIVE: Neonatal screening and earlier diagnosis have improved the prognosis
      of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency, which
      causes a need to refine the staging of the pigmentary chorioretinopathy and thus
      improve monitoring and comparability of patients under dietary therapy. METHODS:
      Seven children with LCHAD deficiency caused by homozygous G1528C mutation
      attended sequential fundus photography for stage 2 chorioretinopathy in 1997
      2006. After arranging 21 pairs of fund us photographs according to the severity
      of the fundus changes,the images best representing 3 different grades of
      pigmentary deposits (P1-P3) and retinal pigment epithelial(RPE) atrophy (A1-A3)
      were chosen as reference photographs.To evaluate the substaging, 29 pairs of
      photographs were graded according to the reference photographs. RESULTS: In the
      assessment of pigmentary deposits, the 3 ophthalmologists agreed in 41% and
      differed by a single substage in 45% of instances (combined weighted K statistic
      was 0.38, indicating moderate agreement). In pairwise comparisons,the weighted K
      statistic ranged from 0.31 to 0.56 (agreement, 71-81%). In the assessment of RPE
      atrophy, all 3 raters agreed in 17% and 2 raters in 70% of instances (combined K
      statistic 0.018, indicating poor agreement). DISCUSSION: Despite variation in
      imaging techniques and limitations in the visual assessment of fundus
      photographs, the agreement obtained in grading the pigmentary deposits was
      comparable to that reported for photographic grading of retinopathy of
      prematurity. We recommend photographic documentation and substaging based on
      reference photographs in the follow-up of LCHAD retinopathy. The refined staging
      allows a more detailed assessment on the progression of the retinopathy and
      optimization of the therapeutic protocols in individual patients and between
      centres using different therapeutic protocols.

PMID- 22473003
TI  - Hanging loose.

PMID- 22473000
TI  - An intercellular pathway for glucose transport into mouse oocytes.
AB  - Glucose is an essential nutrient for mammalian cells. Emerging evidence suggests
      that glucose within the oocyte regulates meiotic maturation. However, it remains
      controversial as to whether, and if so how, glucose enters oocytes within cumulus
      oocyte complexes (COCs). We used a fluorescent glucose derivative (6-NBDG) to
      trace glucose transport within live mouse COCs and employed inhibitors of glucose
      transporters (GLUTs) and gap junction proteins to examine their distinct roles in
      glucose uptake by cumulus cells and the oocyte. We showed that fluorescent
      glucose enters both cumulus-enclosed and denuded oocytes. Treating COCs with GLUT
      inhibitors leads to simultaneous decreases in glucose uptake in cumulus cells and
      the surrounded oocyte but no effect on denuded oocytes. Pharmacological blockade
      of of gap junctions between the oocyte and cumulus cells significantly inhibited
      fluorescent glucose transport to oocytes. Moreover, we find that both in vivo
      hyperglycemic environment and in vitro high-glucose culture increase free glucose
      levels in oocytes via gap junctional channels. These findings reveal an
      intercellular pathway for glucose transport into oocytes: glucose is taken up by
      cumulus cells via the GLUT system and then transferred into the oocyte through
      gap junctions. This intercellular pathway may partly mediate the effects of high
      glucose condition on oocyte quality.

PMID- 22473004
TI  - Enhanced TLR-induced NF-kappaB signaling and type I interferon responses in NLRC5
      deficient mice.
AB  - Nod-like receptors (NLRs) are intracellular sensors that respond to a variety of
      pathogen and intracellular danger signals to induce innate immune responses.
      NLRC5 has recently been identified to be an important regulator of NF-kappaB,
      type I interferon (IFN) and inflammasome signaling pathways, but the in vivo
      function and mechanisms of NLRC5 remain to be defined. Here, we describe the
      generation and characterization of NLRC5 knockout mice. We show that induction of
      NLRC5 expression by Toll-like receptor (TLR) ligand or cytokine stimulation
      requires the signal transducers and activators of transcription (Stat)1-mediated
      signaling pathway. NLRC5 ablation reduces MHC class I expression, and enhances
      IKK and IRF3 phosphorylation in response to TLR stimulation or viral infection.
      Consistent with these observations, we found that NLRC5 deficiency enhanced IL-6
      and IFN-beta production in mouse embryonic fibroblasts (MEFs), peritoneal
      macrophages and bone marrow-derived macrophages (BMMs), but not bone marrow
      derived dendritic cells (BMDCs) after LPS stimulation or vesicular stomatitis
      virus (VSV) infection. Furthermore, we found that NLRC5-deficient mice produced
      higher amounts of IL-6 and IFN-beta in the sera when they were challenged with
      LPS or infected with VSV. Taken together, these results provide in vivo evidence
      that NLRC5 plays critical roles in MHC class I expression, innate immune
      signaling and antiviral innate immune responses, thus serving as an important
      target for modulating innate immune signaling and regulation.

PMID- 22473005
TI  - The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated
      GLUT4 translocation.
AB  - Insulin-stimulated glucose uptake by the glucose transporter GLUT4 plays a
      central role in whole-body glucose homeostasis, dysregulation of which leads to
      type 2 diabetes. However, the molecular components and mechanisms regulating
      insulin-stimulated glucose uptake remain largely unclear. Here, we demonstrate
      that Axin interacts with the ADP-ribosylase tankyrase 2 (TNKS2) and the kinesin
      motor protein KIF3A, forming a ternary complex crucial for GLUT4 translocation in
      response to insulin. Specific knockdown of the individual components of the
      complex attenuated insulin-stimulated GLUT4 translocation to the plasma membrane.
      Importantly, TNKS2(-/-) mice exhibit reduced insulin sensitivity and higher blood
      glucose levels when re-fed after fasting. Mechanistically, we demonstrate that in
      the absence of insulin, Axin, TNKS and KIF3A are co-localized with GLUT4 on the
      trans-Golgi network. Insulin treatment suppresses the ADP-ribosylase activity of
      TNKS, leading to a reduction in ADP ribosylation and ubiquitination of both Axin
      and TNKS, and a concurrent stabilization of the complex. Inhibition of Akt, the
      major effector kinase of insulin signaling, abrogates the insulin-mediated
      complex stabilization. We have thus elucidated a new protein complex that is
      directly associated with the motor protein kinesin in insulin-stimulated GLUT4
      translocation.

PMID- 22473006
TI  - Reprogramming based gene therapy for inherited red blood cell disorders.

PMID- 22473007
TI  - Cardiac biomarkers and noninvasive predictors of atherosclerosis in chronic
      peritoneal dialysis patients.
AB  - BACKGROUND: We investigated the relationship among serum cardiac biomarkers
      including N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin
      T (cTnT), uric acid and high-sensitive C-reactive protein (hs-CRP) and
      noninvasive predictors of atherosclerosis including carotid intima-media
      thickness (IMT), aortic stiffness (pulse wave velocity (PWV)) and transthoracic
      coronary flow reserve (CFR) in peritoneal dialysis (PD) patients. METHODS: 37 PD
      patients were included in the study. We measured (1) carotid IMT, (2) PWV and
      augmentation index (AIx), and (3) CFR. Simultaneous measurements of serum NT-pro
      BNP, cTnT, uric acid and hs-CRP were also performed. Associations among these
      variables were analyzed. RESULTS: cTnT was significantly associated with carotid
      IMT (r = 0.747, p < 0.001), PWV (r = 0.431, p = 0.035) and CFR (r = -0.439, p =
      0.007). In multivariate analysis, cTnT was a significant independent predictor of
      carotid IMT (beta = 4.446, p < 0.001) and CFR (beta = -2.272, p = 0.013).
      Patients with high cTnT levels (>=0.01 ng/ml) significantly hadhigher carotid IMT
      and PWV values. Only the aortic PWV significantly correlated with residual renal
      function (r = -0.574, p = 0.004). CONCLUSIONS: Serum cTnT appeared to be a useful
      clinical biomarker for evaluating noninvasive predictors of atherosclerosis in
      chronic PD patients. Arterial stiffness as determined by PWV is also correlated
      with residual renal function.

PMID- 22473008
TI  - Decreased extra-renal urate excretion is a common cause of hyperuricemia.
AB  - ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of
      which raises gout/hyperuricemia risk. Generally, hyperuricemia has been
      classified into urate 'overproduction type' and/or 'underexcretion type' based
      solely on renal urate excretion, without considering an extra-renal pathway. Here
      we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is
      a common mechanism of hyperuricemia. Clinical parameters, including urinary urate
      excretion, are examined in 644 male outpatients with hyperuricemia.
      Paradoxically, ABCG2 export dysfunction significantly increases urinary urate
      excretion and risk ratio of urate overproduction. Abcg2-knockout mice show
      increased serum uric acid levels and renal urate excretion, and decreased
      intestinal urate excretion. Together with high ABCG2 expression in extra-renal
      tissues, our data suggest that the 'overproduction type' in the current concept
      of hyperuricemia be renamed 'renal overload type', which consists of two subtypes
      'extra-renal urate underexcretion' and genuine 'urate overproduction'-providing a
      new concept valuable for the treatment of hyperuricemia and gout.

PMID- 22473009
TI  - Demonstration of a stable ultrafast laser based on a nonlinear microcavity.
AB  - Ultrashort pulsed lasers, operating through the phenomenon of mode-locking, have
      had a significant role in many facets of our society for 50 years, for example,
      in the way we exchange information, measure and diagnose diseases, process
      materials, and in many other applications. Recently, high-quality resonators have
      been exploited to demonstrate optical combs. The ability to phase-lock their
      modes would allow mode-locked lasers to benefit from their high optical spectral
      quality, helping to realize novel sources such as precision optical clocks for
      applications in metrology, telecommunication, microchip-computing, and many other
      areas. Here we demonstrate the first mode-locked laser based on a microcavity
      resonator. It operates via a new mode-locking method, which we term filter-driven
      four-wave mixing, and is based on a CMOS-compatible high quality factor microring
      resonator. It achieves stable self-starting oscillation with negligible amplitude
      noise at ultrahigh repetition rates, and spectral linewidths well below 130  kHz.

PMID- 22473010
TI  - The self-interaction of native TDP-43 C terminus inhibits its degradation and
      contributes to early proteinopathies.
AB  - The degraded, misfolded C terminus of TAR DNA-binding protein-43 is associated
      with a wide spectrum of neurodegenerative diseases, particularly frontotemporal
      lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral
      sclerosis. However, the precise mechanism of pathological cleavage of the TAR DNA
      binding protein-43 remains unknown. Here we show that the TAR DNA-binding protein
      43 C-terminal protein physically interacts with itself or with the cellular
      folded yeast prion domain of Sup35 forming dynamic aggregates. This prion-like
      nature governs known cellular functions of the TAR DNA-binding protein-43,
      including subcellular localisation and exon skipping of the cystic fibrosis
      transmembrane conductance regulator. Significantly, mutants with a failure to
      engage in prion-like interactions are processed into an ~24-kDa C-terminal
      fragment of the TAR DNA-binding protein-43. The estimated cleavage site of
      degraded TAR DNA-binding protein-43 fragments corresponds to the pathological
      cleavage site identified in patients with the TAR DNA-binding protein-43
      proteinopathies. Consistently, epigallocatechin gallate constrains prion-like
      interactions, attenuating pathological-like degradation. Thus, the native folding
      of TAR DNA-binding protein-43 C terminus acts as a guardian of pathogenesis,
      which is directly associated with loss-of-function.

PMID- 22473011
TI  - BCR-signalling synergizes with TLR-signalling for induction of AID and
      immunoglobulin class-switching through the non-canonical NF-kappaB pathway.
AB  - By diversifying antibody biological effector functions, class switch DNA
      recombination has a central role in the maturation of the antibody response. Here
      we show that BCR-signalling synergizes with Toll-like receptor (TLR) signalling
      to induce class switch DNA recombination. BCR-signalling activates the non
      canonical NF-kappaB pathway and enhances the TLR-dependent canonical NF-kappaB
      pathway, thereby inducing activation-induced cytidine deaminase (AID), which is
      critical for class switch DNA recombination. Escherichia coli lipopolysaccharide
      (LPS) triggers dual TLR4/BCR-signalling and induces hallmarks of BCR-signalling,
      including CD79a phosphorylation and Ca(2+) mobilization, and activates both the
      NF-kappaB pathways to induce AID and class switch DNA recombination in a PI(3)K
      p85alpha-dependent fashion. CD40-signalling activates the two NF-kappaB pathways
      to induce AID and class switch DNA recombination independent of BCR-signalling.
      Finally, dual BCR/TLR-engaging NP-lipopolysaccharide effectively elicits class
      switched NP-specific IgG3 and IgG2b in mice. Thus, by integrating signals of the
      non-canonical and canonical NF-kappaB pathways, BCR and TLRs synergize to induce
      AID and T-cell-independent class switch DNA recombination.

PMID- 22473012
TI  - Growth of non-phototrophic microorganisms using solar energy through mineral
      photocatalysis.
AB  - Phototrophy and chemotrophy are two dominant modes of microbial metabolism. To
      date, non-phototrophic microorganisms have been excluded from the solar light
      centered phototrophic metabolism. Here we report a pathway that demonstrates a
      role of light in non-phototrophic microbial activity. In lab simulations, visible
      light-excited photoelectrons from metal oxide, metal sulfide, and iron oxide
      stimulated the growth of chemoautotrophic and heterotrophic bacteria. The
      measured bacterial growth was dependent on light wavelength and intensity, and
      the growth pattern matched the light absorption spectra of the minerals. The
      photon-to-biomass conversion efficiency was in the range of 0.13-1.900/00.
      Similar observations were obtained in a natural soil sample containing both
      bacteria and semiconducting minerals. Results from this study provide evidence
      for a newly identified, but possibly long-existing pathway, in which the
      metabolisms and growth of non-phototrophic bacteria can be stimulated by solar
      light through photocatalysis of semiconducting minerals.

PMID- 22473013
TI  - Drosophila follicle stem cells are regulated by proliferation and niche adhesion
      as well as mitochondria and ROS.
AB  - The mechanisms underlying adult stem cell behaviour are likely to be diverse and
      have not yet been investigated systematically. Here we conducted an unbiased
      genetic screen using Drosophila ovarian follicle stem cells to probe essential
      functions regulating self-renewal of epithelial stem cells. Surprisingly, we find
      that niche adhesion emerges as the most commonly affected essential stem cell
      property, and that proliferation is critical for stem cell maintenance. We also
      find that PI3K pathway activation enhances follicle stem cell function, whereas
      mitochondrial dysfunction and reactive oxygen species production lead to stem
      cell loss. Moreover, we find that most genes required specifically in the stem
      cell of the follicle stem cell lineage are widely expressed but are not required
      for the maintenance of ovarian germline stem cells. These findings highlight the
      fundamental characteristics of follicle stem cells as an important stem cell
      paradigm that contrasts with some other stem cell models, where repression of
      differentiation or relative quiescence is crucial.

PMID- 22473014
TI  - Ultrathin and lightweight organic solar cells with high flexibility.
AB  - Application-specific requirements for future lighting, displays and photovoltaics
      will include large-area, low-weight and mechanical resilience for dual-purpose
      uses such as electronic skin, textiles and surface conforming foils. Here we
      demonstrate polymer-based photovoltaic devices on plastic foil substrates less
      than 2 MUm thick, with equal power conversion efficiency to their glass-based
      counterparts. They can reversibly withstand extreme mechanical deformation and
      have unprecedented solar cell-specific weight. Instead of a single bend, we form
      a random network of folds within the device area. The processing methods are
      standard, so the same weight and flexibility should be achievable in light
      emitting diodes, capacitors and transistors to fully realize ultrathin organic
      electronics. These ultrathin organic solar cells are over ten times thinner,
      lighter and more flexible than any other solar cell of any technology to date.

PMID- 22473015
TI  - Micelles based on gold-glycopolymer complexes as new chemotherapy drug delivery
      agents.
AB  - Polymeric versions of deacetylated auranofin, a gold complex with a sugar ligand,
      were prepared by post-modifying RAFT glycopolymers. Micellisation of a block
      copolymer containing pendant Au(I) units produced nanoparticles with an increased
      anti-proliferative effect against OVCAR-3 human ovarian carcinoma cells.

PMID- 22473016
TI  - Major impact of body position on arterial stiffness indices derived from radial
      applanation tonometry in pregnant and nonpregnant women.
AB  - OBJECTIVE: To evaluate the impact of body position on the arterial stiffness
      indices provided by radial applanation tonometry in pregnant and nonpregnant
      women. METHODS: Twenty-four young women (18-30 years) in the third trimester of a
      normal pregnancy and 20 healthy nonpregnant women of the same age were enrolled.
      In each, applanation tonometry was carried out in the sitting and supine
      position. The following stiffness indices were analyzed: systolic augmentation
      index (sAix), sAix adjusted for heart rate (sAix@75) and diastolic augmentation
      index (dAix), all expressed in % of central aortic pulse pressure. RESULTS: The
      sAix was apparently not influenced by body position, but the transition from
      seated to supine was associated with a substantial decrease in heart rate. When
      correcting for this confounder by calculating the sAix@75, systolic augmentation
      was substantially lower when individuals were supine (mean +/- SD: nonpregnant
      3.0 +/- 14.4%, pregnant 8.8 +/- 9.7%) than when they were sitting (nonpregnant
      5.7 +/- 13.0%, pregnant 11.1 +/- 83%, P = 0.005 supine vs. seated in both study
      groups, P > 0.2 for pregnant vs. nonpregnant). The influence of body position on
      the dAix went in the opposite direction (supine: nonpregnant 9.7 +/- 6.6%,
      pregnant 4.4 +/- 3.5%; seated: nonpregnant 7.7 +/- 5.8%, pregnant 3.3 +/- 2.4%, P
      < 0.00001 supine vs. seated in both study groups, P = 0.001 for pregnant vs.
      nonpregnant). CONCLUSION: Body position has a major impact on the pattern of
      central aortic pressure augmentation by reflected waves in healthy young women
      examined either during third trimester pregnancy or in the nonpregnant state.

PMID- 22473017
TI  - The quantitative relationship between road traffic noise and hypertension:  a
      meta-analysis.
AB  - OBJECTIVE: Reviews have suggested that road noise exposure is associated with
      high blood pressure (hypertension). No reliable exposure-response relationship is
      as yet available. A meta-analysis was carried out in order to derive a
      quantitative exposure-response relationship between the exposure to road traffic
      noise and the prevalence of hypertension, and to gain some insight into the
      sources of heterogeneity among study results. METHODS: Twenty-seven observational
      studies published between 1970 and 2010 in English, German or Dutch, were
      evaluated. Finally, the results of 24 studies were included into the data
      aggregation. RESULTS: Road traffic noise was positively and significantly
      associated with hypertension: Data aggregation revealed an odds ratio (OR) of
      1.034 [95% confidence interval (CI) 1.011-1.056] per 5 dB(A) increase of the 16 h
      average road traffic noise level (LAeq16hr) [range 45-75 dB(A)]. Important
      sources of heterogeneity were the age and sex of the population under study, the
      way exposure was ascertained, and the noise reference level used. Also the way
      noise was treated in the statistical model and the minimum years of residence of
      the population under study, gave an explanation of the observed heterogeneity. No
      definite conclusions can be drawn about the threshold value for the relationship
      between road traffic noise and the prevalence of hypertension. CONCLUSION: Based
      on the meta-analysis, a quantitative relationship is derived that can be used for
      health impact assessment. The results of this meta-analysis are consistent with a
      slight increase of cardiovascular disease risk in populations exposed to
      transportation noise.

PMID- 22473018
TI  - Intra-familial aggregation and heritability of aortic versus brachial pulse
      pressure after imputing pretreatment values in a community of African ancestry.
AB  - AIM: To compare the intra-familial aggregation and heritability of central
      (aortic) (PPc) versus peripheral (brachial) (PPp) pulse pressure after imputing
      pretreatment blood pressures (BPs) in treated participants in a community of
      black African ancestry. METHODS: Central PPc [generalized transfer function (GTF)
      and radial P2-derived] was determined with applanation tonometry at the radial
      artery (SphygmoCor software) in 946 participants from 258 families with 23
      families including three generations from an urban developing community of black
      Africans. In the 24.1% of participants receiving antihypertensive treatment,
      pretreatment brachial BP was imputed from published overall averaged effects of
      therapy grouped by class and dose, specific for groups of black African descent.
      From these data PPc was estimated from proportionate differences in central
      aortic and brachial PP. Heritability estimates were determined from SAGE
      software. Echocardiography was evaluated in 507 participants in order to
      determine stroke volume. RESULTS: With adjustments for confounders, parent-child
      (P < 0.05) and sibling-sibling (P < 0.0005) correlations were noted for log PPc,
      whilst for log PPp only sibling-sibling correlations were noted. No mother-father
      correlations were noted for either PPc or PPp. Independent of confounders the
      heritability for log GTF-derived (h = 0.33 +/- 0.07, P < 0.0001) and P2-derived
      (h = 0.30 +/- 0.07, P < 0.0001) PPc was greater than the heritability for log PPp
      (h = 0.11 +/- 0.06, P < 0.05) (P < 0.05 for comparison of heritability
      estimates). CONCLUSION: After imputing pretreatment BP values, central aortic PP
      is significantly more inherited than brachial PP. These data suggest that in
      groups of African descent the genetic determinants of PP may be underestimated
      when employing brachial rather than central aortic PP measurements.

PMID- 22473019
TI  - Blood pressure and heart rate predict outcome in patients acutely admitted with
      suspected myocarditis without previous heart failure.
AB  - OBJECTIVE: The study investigated the prognostic impact of blood pressure and
      heart rate in patients acutely admitted with suspected myocarditis without
      previous heart failure who underwent endomyocardial biopsy. METHODS AND RESULTS:
      In our prospectively planned study SBP, DBP, mean arterial blood pressure (MAP)
      and ECGs on admission were analyzed retrospectively in 175 patients with
      suspected myocarditis, who underwent endomyocardial biopsy between 1994 and 2007.
      Patients were followed up for a median of 53 +/- 41 months, corresponding to a
      total follow-up of 9337 patient months. The primary endpoint was the time to
      cardiac death or heart transplantation, which occurred in 39 patients (22%).
      Baseline SBP was inversely associated with primary endpoint occurrence. Per 1
      mmHg increase in SBP, the hazard ratio for the primary endpoint decreased by 4.3%
      [hazard ratio = 0.96, confidence interval (CI) = 0.94-0.98, P < 0.001]. The
      increased risk at a SBP below the mean value was confirmed after adjusting for
      the known independent predictors immunohistological signs of inflammation in
      biopsy samples, New York Heart Association functional class, and lack of beta
      blocker treatment (hazard ratio = 2.78, CI = 1.25-6.18, P = 0.012). In the
      presence of all risk predictors, hazard ratio for primary endpoint was 4.97 (CI =
      2.28-10.83, P < 0.001). In a subgroup analysis of patients without beta-blocker
      treatment, atrial fibrillation or pacemaker, a high heart rate was also
      associated with poor outcome (hazard ratio = 2.92, CI = 1.02-8.29, P = 0.045).
      CONCLUSION: In patients with suspected myocarditis without previous chronic heart
      failure low SBP, DBP and MAP were predictors of poor outcome. However, in
      patients not treated with beta-blockers, a high heart rate was a predictor for
      cardiac death or heart transplantation.

PMID- 22473020
TI  - Diastolic blood pressure drop after standing as a clinical sign for increased
      mortality in older falls clinic patients.
AB  - BACKGROUND: Orthostatic hypotension, postprandial hypotension, and carotid sinus
      hypersensitivity are hypotensive syndromes with high prevalence in older people.
      However, their pathophysiology and prognostic significance remain largely
      unknown. METHODS: In a retrospective cohort study of 313 consecutive patients
      visiting our falls outpatient clinic, we examined the clustering of orthostatic
      hypotension, postprandial hypotension, and carotid sinus hypersensitivity in the
      same patients, which might reflect a shared similar pathophysiology. The value of
      hypotensive syndrome presence and the degree of blood pressure decline as
      prognostic indicators for mortality were assessed using Cox proportional hazards
      analyses. RESULTS: In 313 patients (mean age 78.7 +/- 8.0 years), 168 of 309
      (54%), 175 of 302 (58%), and 143 of 272 (53%) were diagnosed with orthostatic
      hypotension, postprandial hypotension, and sinus carotid hypersensitivity,
      respectively. There was no clustering of the hypotensive syndromes. During a
      median follow-up of 23.0 months, 58 (19%) patients died. Orthostatic hypotension,
      but not postprandial hypotension or carotid sinus hypersensitivity, predicted
      mortality [hazard ratio 1.97; 95% confidence interval (CI) 1.11-3.47]. After
      adjusting for age, comorbidity and other baseline characteristics, this
      relationship was no longer significant. However, orthostatic hypotension with
      severe diastolic blood pressure decline of at least 20 mmHg remained a powerful
      independent predictor of mortality (hazard ratio 2.50; 95% CI 1.20-5.22).
      CONCLUSIONS: In falls clinic patients, hypotensive syndromes did not cluster and
      did not independently predict mortality. However, orthostatic hypotension with
      severe diastolic blood pressure decline was a powerful independent predictor of
      mortality and might be used prognostically as an easily available cardiovascular
      sign of increased mortality risk.

PMID- 22473021
TI  - Sympathetic nerve activity in women 40 years after a hypertensive pregnancy.
AB  - OBJECTIVES: Epidemiological studies show that women with pregnancies complicated
      by hypertension have an increased risk of cardiovascular morbidity later in life.
      The underlying mechanisms to the risk increase remain largely unknown. This study
      evaluated sympathetic nerve activity in women with hypertensive pregnancies 40
      years earlier compared to women with normotensive pregnancies. We hypothesized
      that sympathetic outflow would be increased in women with previous hypertensive
      pregnancies and that this partly may explain the increased cardiovascular risk.
      METHODS: Sympathetic nerve activity to the muscle vascular bed [muscle
      sympathetic nerve activity (MSNA)] was recorded in 28 women, 18 with and 10
      without a hypertensive manifestation during pregnancy. Women were also examined
      with ambulatory blood pressure measurements, pulse wave velocity, blood pressure
      response during Stroop test and laboratory analysis. RESULTS: Women with previous
      hypertensive pregnancies did not show an increased sympathetic outflow compared
      to women with normotensive pregnancies. In eight women with treated hypertension
      sympathetic outflow was increased compared to normotensive women despite similar
      ambulatory blood pressure values (P < 0.05). During Stroop test the hypertensive
      women showed increased systolic blood pressure and also displayed the highest
      augmentation index compared to normotensive women (P < 0.05). CONCLUSION:
      Hypertensive pregnancies per se were not associated with increased sympathetic
      outflow 40 years later. The increased cardiovascular risk in women with previous
      hypertensive pregnancies cannot be explained by chronic activation of the
      sympathetic nervous system.In women with previous hypertensive pregnancies, still
      hypertensive though well controlled, sympathetic outflow and arterial stiffness
      were, however, increased compared to normotensive counterparts.

PMID- 22473022
TI  - [2+2] photocycloadditions of thiomaleimides.
AB  - Thiomaleimides, generated by the addition of bromomaleimides to thiols including
      cysteine, undergo highly efficient [2+2] photocycloadditions.

PMID- 22473023
TI  - Physical activity and functional limitations in older adults: the influence of
      self-efficacy and functional performance.
AB  - OBJECTIVES: Data from the Healthy Aging Network (HAN) study (Prohaska, T.,
      Eisenstein, A., Satariano, W., Hunter, R., Bayles, C., Kurtovich, E., ... Ivey,
      S. [2009]. Walking and the preservation of cognitive function in older
      populations. The Gerontologist, 49[Suppl. 1], S86-S93; and Satariano, W., Ivey,
      S., Kurtovich, E., Kealey, M., Hubbard, A., Bayles, C., ... Prohaska, T. [2010].
      Lower-body function, neighborhoods, and walking in an older population. American
      Journal of Preventive Medicine, 38, 419-428.) were used to examine the
      relationships among physical activity, self-efficacy, functional performance, and
      limitations. METHOD: Interviews were conducted within homes and senior centers in
      4 geographic regions across the United States. Participants were 884 older adults
      (M age = 74.8; 77% female; 35% minority status) who completed measures of walking
      behavior, way-finding self-efficacy, walking self-efficacy, functional
      performance, functional limitations, and demographic characteristics. RESULTS:
      Path analysis within a covariance modeling framework revealed significant direct
      effects of walking on self-efficacy constructs, functional performance on
      functional limitations, and efficacy on limitations. Additionally, significant
      indirect effects were also found, including walking on limitations via walking
      self-efficacy and performance and walking self-efficacy on limitations via
      performance. Furthermore, we found support for invariance of the model across
      geographical grouping. DISCUSSION: Our findings provide further validation for an
      efficacy-based model of functional limitations. Walking-related efficacy may help
      reduce or possibly delay the onset of functional limitations.

PMID- 22473024
TI  - HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated
      tuberculous meningitis initiating antiretroviral therapy in Vietnam.
AB  - BACKGROUND: Access to antiretroviral therapy (ART) for HIV-infected individuals
      in Vietnam is rapidly expanding, but there are limited data on HIV drug
      resistance (HIVDR) to guide ART strategies. METHODS: We retrospectively conducted
      HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled
      trial of immediate versus deferred ART in individuals with HIV-associated
      tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations
      were identified by population sequencing of the HIV pol gene and were defined
      based on 2009 WHO surveillance drug resistance mutations (SDRMs). RESULTS: We
      successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were
      subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%)
      subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase
      inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside
      reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A),
      1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors.
      After 6 months of ART, eight subjects developed protocol-defined virological
      failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations
      with high-level resistance to NNRTIs and three had mutations with high-level
      resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre
      existing HIVDR mutations on treatment outcome could not be accurately assessed.
      CONCLUSIONS: The prevalence of WHO SDRMs in ART-naive individuals with HIV
      associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs
      identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard
      first-line ART regimens in Vietnam.

PMID- 22473025
TI  - A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with
      other drugs that modulate ethanol intake in rats responding under a multiple
      schedule.
AB  - Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs
      (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male
      rats responding under a multiple schedule of food and ethanol presentation to
      determine their selectivity for decreasing ethanol-maintained responding. DHEA
      and 7-keto DHEA significantly decreased both ethanol-maintained and food
      maintained responding, compared with the control, while also decreasing the blood
      ethanol concentration (BEC). Acute ethanol administration also decreased
      responding for both food and ethanol; however, ethanol-maintained responding was
      more potently decreased than food-maintained responding. BEC remained relatively
      stable after increasing ethanol doses. Among the other drugs tested, RO15-4513
      was the most selective for decreasing ethanol-maintained responding compared with
      food-maintained responding, and it decreased BECs as ethanol-maintained
      responding decreased. The largest dose of rauwolscine significantly decreased
      responding for food, whereas it did not affect ethanol-maintained responding
      compared with the control. Low to intermediate doses of rauwolscine produced
      small, nonsignificant increases in ethanol-maintained responding and BECs.
      Chlordiazepoxide produced significant decreases in food-maintained responding and
      the dose of ethanol presented, but only at the highest dose tested. Although DHEA
      and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as
      ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be
      valuable pharmacological tools in the development of new treatments for alcohol
      abuse and dependence.

PMID- 22473026
TI  - Impact of altitude on predicting midterm outcome in patients with ST elevation
      myocardial infarction.
AB  - This study investigated the effects of altitude on occurrence of mid-term
      negative events among patients presenting with ST elevation myocardial infarction
      (STEMI). This study enrolled 492 patients with STEMI. 119 of those patients were
      living at an intermediate altitude (1960 m, Group I) and 373 were living at sea
      level (0 m, Group II). There was no significant difference between the different
      altitude groups in terms of the incidence of cardiac death, urgent target vessel
      revascularization (TVR), stroke/transient ischemic attack (TIA) and composite
      endpoints. However, Group I had a significantly higher reinfarction incidence
      when compared with the Group II. Independent predictors of 6-month composite
      endpoints were history of statin use, presentation with acute stent thrombosis,
      peak CK-MB level, success of procedure, Killip classification, and left
      ventricular ejection fraction. In conclusion, altitude status and altitude
      related hematologic changes had no influence over the mid-term outcomes in STEMI
      patients treated with percutaneous intervention. 

PMID- 22473027
TI  - A common VWF exon 28 haplotype in the Turkish population.
AB  - An increasing number of mutations and polymorphisms have been identified in the
      von Willebrand factor (VWF) gene of patients with von Willebrand disease (VWD).
      Most of the sequence alterations are within exon 28, duplicated in the VWF
      pseudogene on chromosome 22. Genetic recombination causing the gene conversion
      between the VWF gene and its pseudogene is associated with multiple substitutions
      in the VWF gene and with VWD. In the present study, VWF gene exon 28 was analyzed
      in 33 patients with VWD by DNA sequencing. A total of 73% of the patients were
      heterozygous for p.D1472H, p.V1485L, p.1500A, p.1501F, p.L1503P, and p.S1506L
      single-nucleotide polymorphisms. Family analysis revealed that the gene
      conversion occurred between the VWF gene and its pseudogene in 3 patients. Case
      control association analysis by Haploview 4.2 did not show an association between
      the haplotype and VWD. In conclusion, a common exon 28 haplotype in the Turkish
      population, which might have arisen from the gene conversion events in the
      founder population, was identified. 

PMID- 22473028
TI  - A novel prothrombin time assay for assessing the anticoagulant activity of oral
      factor Xa inhibitors.
AB  - Conventional prothrombin time (PT) assays have limited sensitivity and dynamic
      range in monitoring the anticoagulant activity of direct factor Xa inhibitors.
      Hence, new assays are needed. We modified a PT assay by adding calcium chloride
      (CaCl2) to the thromboplastin reagent to increase assay dynamic range and improve
      sensitivity. Effects of calcium and sodium ion concentrations, and sample
      handling, were evaluated to optimize assay performance. Increasing concentrations
      of calcium ions produced progressive increases in PT across the factor Xa
      inhibitor concentrations of 0 to 2500 nmol/L for razaxaban and apixaban. The
      greatest effect was seen when the thromboplastin reagent was diluted 1:2.25 with
      100 mmol/L CaCl2 (thus selected for routine use). The optimized assay showed an
      interassay precision of 1.5 to 9.3 percentage coefficient of variation (%CV) for
      razaxaban and 3.1 to 4.6 %CV for apixaban. We conclude that the modified PT assay
      is likely to be suitable as a pharmacodynamic marker for activity at therapeutic
      concentrations of factor Xa inhibitors. 

PMID- 22473029
TI  - Assessment of incompletely excised basal cell carcinomas in six facial areas:
      influence of elastosis.
AB  - BACKGROUND: Incomplete excision of non-melanoma skin cancer is a clinical
      indicator of surgical care. With most basal cell carcinomas arising on the face
      and considering the cosmetic and functional structures involved, it is
      interesting to identify what are the areas within the face with more likelihood
      of incomplete excision and the factors implicated. The aim of this study was to
      identify those areas and possible predictive factors. Six anatomical regions were
      considered and studied selectively. METHOD: A monocentric study was performed
      reviewing all facial basal cell carcinomas excised at our center during 2010.
      Data were analyzed using SPSS software. RESULTS: 202 lesions from 202 subjects
      were studied. The percentage of incomplete excision was 17.07%. CONCLUSION:
      Lesions located in the orbitopalpebral and auricular areas and those with
      moderate to severe grade of associated elastosis are more likely to be
      incompletely excised. Wider surgical margins are observed in frontal, malar and
      labial areas which are distant from functional structures. The following tumor
      features were found to be a risk factor for incomplete resection: morpheic or
      superficial histology, large lesions (>20 mm) and thick lesions (>6 mm).

PMID- 22473030
TI  - What is the role of serial high-sensitivity troponin measurements in chronic
      heart failure?

PMID- 22473031
TI  - Direct-to-consumer disease screening with finger-stick testing: online patient
      safety risks.

PMID- 22473033
TI  - Real time quantitative amplification detection on a microarray: towards high
      multiplex quantitative PCR.
AB  - Quantitative real-time polymerase chain reaction (qrtPCR) is widely used as a
      research and diagnostic tool. Notwithstanding its many powerful features, the
      method is limited in the degree of multiplexing to about 6 due to spectral
      overlap of the available fluorophores. A new method is presented that allows
      quantitative amplification detection at higher multiplexing by the integration of
      amplification in solution and monitoring via hybridization to a microarray in
      real-time. This method does not require any manipulation of the PCR product and
      runs in a single closed chamber. Employing labeled primers, one of the main
      challenges is to measure surface signals against a high fluorescence background
      from solution. A compact, confocal scanner is employed, based on miniaturized
      optics from DVD technology and combined with a flat thermocycler for simultaneous
      scanning and heating. The feasibility of this method is demonstrated in
      singleplex with an analytical sensitivity comparable to routine qrtPCR.

PMID- 22473034
TI  - Effects of bone marrow mesenchymal stem cells on cell proliferation and growth
      factor expression of limbal epithelial cells in vitro.
AB  - Mesenchymal stem cells (MSCs) can play an active role in there construction of
      the ocular surface; however, the mechanisms by which the implanted MSCs exert
      their effects remain elusive. In the present study, we investigated the
      influences of MSCs on cell proliferation and growth factor expression of corneal
      limbal epithelial cells (LECs) in vitro. Rat LECs were either cocultured with rat
      MSCs or cultured in rat MSC condition edmedium. The harvested LECs were subjected
      to light microscopy, MTT assay, bromodeoxyuridine (BrdU)staining, flow cytometry
      and real-time quantitative RT-PCR analysis, respectively. Light microscopy showed
      that coculturing of LECs with MSCs significantly increased the proliferation of
      LECs. The MTT assay showed that MSC-conditioned medium significantly increased
      the cell viability of LECs compared to those incubated with plain medium. BrdU
      immunostaining and flow-cytometric analysis of the cell cycle showed that the
      cell proliferation rate of LECs cocultured with MSCs was significantly higher
      than that of LECs cultured alone. Real-time quantitative RT-PCR analysis showed
      that expression of epidermal growth factor in LECs cocultured with MSCs was
      significantly higher than that in LECs cultured alone. However, expression of
      basic fibroblast growth factor showed no difference under the two culture
      conditions. These results indicate that MSCs promote the survival and
      proliferation of LECs, and these effects may be mediated ina paracrine manner.

PMID- 22473035
TI  - The plasma permeability factor in nephrotic syndrome: indirect evidence in
      pediatric peritoneal dialysis.
AB  - BACKGROUND: Nephrotic syndrome (NS) in children has been associated with a
      systemic circulating permeability factor. Therefore, once peritoneal dialysis
      (PD) has been started, peritoneal protein losses should be higher in the
      nephrotic than in the non-nephrotic population. OBJECTIVE: We compared peritoneal
      protein losses in children with and without NS on PD. METHODS: Our retrospective
      4-year study analyzed Hispanic patients with NS under PD. Data at dialysis entry
      and 6 months later were compared. Nutritional support was given according to
      recommended dietary allowances and recommendations from the Kidney Disease
      Outcomes Quality Initiative. Clinical and biochemical data were obtained, and 24
      hour dialysate and urine samples were collected to measure protein losses.
      Dialysis dose (Kt/V), daily protein intake (DPI), normalized protein equivalent
      of nitrogen appearance (nPNA), peritoneal equilibration test (PET), and
      peritonitis rate were determined. All measurements took place at least 4 weeks
      after resolution of a peritonitis episode. All patients received automated PD
      using a HomeChoice PD System cycler (Baxter Healthcare Corporation, Deerfield,
      IL, USA), with an exchange volume of 1100 mL/m(2) and a dextrose concentration of
      1.5% - 2.5%. A control group of non-NS children on PD matched by age and sex were
      also studied. Data are reported as mean +/- standard deviation. Differences
      between groups were calculated using the Mann-Whitney U-test, and p < 0.05 was
      considered significant. RESULTS: Each study group consisted of 10 patients [NS
      patients: 4 boys, mean age of 7.3 +/- 4.1 years; control patients: 6 boys, mean
      age of 7.2 +/- 4.7 years (p = nonsignificant)]. In the group with NS, 8 patients
      were diagnosed by biopsy as having focal segmental glomerulosclerosis, and 2 as
      having minimal-change disease. At study entry, patients with NS had hourly
      urinary protein losses of 398 +/- 313 mg/m(2) and daily peritoneal protein losses
      of 3.4 +/- 1.9 g/m(2), compared with 29.9 +/- 31 mg/m(2) and 1.5 +/- 1.1 g/m(2)
      respectively in the control group (p < 0.05). The same statistical difference was
      found 6 months later. We observed no statistical differences in PET results,
      daily exchange volume, and mean dextrose concentration of dialysate. Similarly,
      no significant between-group differences were observed for Kt/V, DPI, nPNA, and
      biochemical parameters. CONCLUSIONS: Hispanic children with NS on PD show higher
      peritoneal protein losses than do their control counterparts. Such differences
      could be secondary to increased peritoneal permeability caused by a systemic
      permeability factor.

PMID- 22473036
TI  - The influence of initial peritoneal transport characteristics, inflammation, and
      high glucose exposure on prognosis for peritoneal membrane function.
AB  - BACKGROUND: Fast transport status, acquired with time on peritoneal dialysis
      (PD), is a pathology induced by peritoneal exposure to bioincompatible solutions.
      Fast transport has important clinical consequences and should be prevented.
      OBJECTIVE: We analyzed the repercussions of initial peritoneal transport
      characteristics on the prognosis for peritoneal membrane function, and also
      whether the influence of peritonitis and high exposure to glucose are different
      according to the initial peritoneal transport characteristics or the moment when
      such events occur. METHODS: The study included 275 peritoneal dialysis patients
      with at least 2 peritoneal function studies (at baseline and 1 year). Peritoneal
      kinetic studies were performed at baseline and annually. Those studies consist of
      a 4-hour dwell with glucose (1.5% during 1981 - 1990, and 2.27% during 1991 -
      2002) to calculate the peritoneal mass transfer coefficients of urea and
      creatinine (milliliters per minute) using a previously described mathematical
      model. RESULTS: Membrane prognosis and technique survival were independent of
      baseline transport characteristics. Fast transport and ultrafiltration (UF)
      failure are reversible conditions, provided that peritonitis and high glucose
      exposure are avoided during the early dialysis period. The first year on PD is a
      main determining factor for the membrane's future, and the mass transfer
      coefficient of creatinine at year 1 is the best functional predictor of future PD
      history. After 5 years on dialysis, permeability frequently increases, and UF
      decreases. Icodextrin is associated with peritoneal protection. CONCLUSIONS:
      Peritoneal membrane prognosis is independent of baseline transport
      characteristics. Intrinsic fast transport and low UF are reversible conditions
      when peritonitis and high glucose exposure are avoided during the early dialysis
      period. Icodextrin helps in glucose avoidance and is associated with peritoneal
      protection.

PMID- 22473037
TI  - Time course of peritoneal function in automated and continuous peritoneal
      dialysis.
AB  - BACKGROUND AND OBJECTIVES: In automated peritoneal dialysis (APD), a patient's
      peritoneal membrane is more intensively exposed to fresh dialysate than it is in
      continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in
      incident peritoneal dialysis (PD) patients, the influence of APD-compared with
      that of CAPD-on peritoneal transport over 4 years. DESIGN, SETTING, PARTICIPANTS,
      AND MEASUREMENTS: Patients were included if at least 2 annual standard
      permeability analyses (SPAs) performed with 3.86% glucose were available while
      the patient was using the same modality with which they had started PD (APD or
      CAPD). Patients were followed until their first modality switch. Differences in
      the pattern of SPA outcomes over time were tested using repeated-measures models
      adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start.
      RESULTS: The 59 CAPD patients enrolled were older than the 47 APD patients
      enrolled (mean age: 58 +/- 14 years vs 49 +/- 14 years; p < 0.01), and they had
      started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in
      solute (p > 0.19) or fluid transport (p > 0.13) were observed. Similarly, free
      water transport (p = 0.43) and small-pore transport (p = 0.31) were not different
      between the modalities. Over time, patients on APD showed a faster decline in
      effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary
      ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not
      change the results. CONCLUSIONS: Compared with patients starting on CAPD, those
      starting on APD experienced a faster decline in ELAR and TCUF. Other transport
      parameters were not different over time between the groups.

PMID- 22473039
TI  - Electroacupuncture and moxibustion decrease renal sympathetic nerve activity and
      retard progression of renal disease in rats.
AB  - BACKGROUND/AIM: Chronic kidney disease (CKD) is an increasing major public health
      problem worldwide. The sympathetic nervous system and nitric oxide play an
      important role in the pathogenesis of CKD. Traditional Chinese medicine has
      accumulated thousands of years of therapeutic experiences. Electroacupuncture
      (EA) and moxibustion (MO) are two such therapeutic strategies. The aim of this
      study was to investigate the renal and hemodynamic effects of EA-MO in an
      experimental model of a CKD. METHODS: Male Wistar rats submitted to 5/6th
      nephrectomy (5/6 NX) were studied for 8 weeks. There were four groups: (1)
      control, normal rats; (2) NX, 5/6 NX only; (3) NX-AS, 5/6 NX and EA-MO session
      using sham points, and (4) NX-AM, 5/6 NX and EA-MO session using real acupoints.
      Biochemical and blood pressure studies, renal sympathetic nerve activity
      measurements, nitric oxide levels and the histopathological indices were
      assessed. RESULTS: The EA- and MO-treated group presented significant improvement
      in all measured functional and histopathological parameters. CONCLUSION: These
      findings suggest that EA-MO had beneficial effects on CKD. This effect was
      probably achieved by the modulation of the renal sympathetic nerve activity and
      nitric oxide levels, leading to decreased blood pressure, which is associated
      with less proteinuria.

PMID- 22473040
TI  - Excited state proton transfer in strongly enhanced GFP (sGFP2).
AB  - Proton transfer is an elementary process in biology. Green fluorescent protein
      (GFP) has served as an important model system to elucidate the mechanistic
      details of this reaction, because in GFP proton transfer can be induced by light
      absorption. We have used pump-dump-probe spectroscopy to study how proton
      transfer through the 'proton-wire' around the chromophore is affected by a
      combination of mutations in a modern GFP variety (sGFP2). The results indicate
      that in H(2)O, after absorption of a photon, a proton is transferred (A* -> I*)
      in 5 ps, and back-transferred from a ground state intermediate (I -> A) in 0.3
      ns, similar to time constants found with GFPuv, although sGFP2 shows less
      heterogeneous proton transfer. This suggests that the mutations left the proton
      transfer largely unchanged, indicating the robustness of the proton-wire. We used
      pump-dump-probe spectroscopy in combination with target analysis to probe
      suitability of the sGFP2 fluorophore for super-resolution microscopy.

PMID- 22473038
TI  - Intrathymic programming of effector fates in three molecularly distinct
      gammadelta T cell subtypes.
AB  - Innate gammadelta T cells function in the early phase of immune responses.
      Although innate gammadelta T cells have often been studied as one homogenous
      population, they can be functionally classified into effector subsets on the
      basis of the production of signature cytokines, analogous to adaptive helper T
      cell subsets. However, unlike the function of adaptive T cells, gammadelta
      effector T cell function correlates with genomically encoded T cell antigen
      receptor (TCR) chains, which suggests that clonal TCR selection is not the main
      determinant of the differentiation of gammadelta effector cells. A high
      resolution transcriptome analysis of all emergent gammadelta thymocyte subsets
      segregated on the basis of use of the TCR gamma-chain or delta-chain indicated
      the existence of three separate subtypes of gammadelta effector cells in the
      thymus. The immature gammadelta subsets were distinguished by unique
      transcription-factor modules that program effector function.

PMID- 22473041
TI  - Differentiation of optic disc edema from optic nerve head drusen with spectral
      domain optical coherence tomography.
AB  - BACKGROUND: To assess the efficacy of quantitative analysis of the optic nerve
      head and peripapillary retinal nerve fiber layer (RNFL) with the spectral-domain
      optical coherence tomography (SD-OCT) in differentiating optic disc edema (ODE)
      from optic nerve head drusen (ONHD). METHODS: Prospective clinical study. Twenty
      five eyes of 25 ODE patients (group 1), 25 eyes of 25 ONHD patients (group 2),
      and 25 eyes of 25 healthy subjects were included. The thickness of the
      peripapillary RNFL, the thickness of the subretinal hyporeflective space (SHYPS),
      the area of the SHYPS, the horizontal length of the optic nerve head, and the
      angle between the temporal RNFL and the optic nerve head (alpha-angle) were
      evaluated with SD-OCT. RESULTS: The mean RNFL thickness was significantly greater
      in group 1 when compared with group 2 and control group (P < 0.001). The receiver
      operating characteristic curve areas for temporal and nasal RNFL thicknesses in
      differentiating group 1 and group 2 were 0.819 and 0.851, respectively (for
      temporal RNFL thickness >101.5 MUm: sensitivity 92%, specificity 65%; for nasal
      RNFL thickness >74.5 MUm: sensitivity 92%, specificity 47%). The mean SHYPS
      thickness, SHYPS area, and degree of the alpha-angle were greater in group 1 when
      compared with group 2 (P < 0.05). For the SHYPS thickness >464 MUm: 85%
      sensitivity and 60% specificity; for the SHYPS area >811 MUm: 85% sensitivity and
      89% specificity; and for the alpha-angle >141 degrees : 77% sensitivity and 95%
      specificity were obtained. CONCLUSION: The quantitative analysis of the optic
      nerve head and peripapillary RNFL with SD-OCT can provide useful data in
      differentiating ODE from ONHD.

PMID- 22473043
TI  - Beer and health: from myths to science.

PMID- 22473045
TI  - Magnesium-catalysed hydroboration of aldehydes and ketones.
AB  - The heteroleptic magnesium alkyl complex [CH{C(Me)NAr}(2)Mg(n)Bu] (Ar = 2,6
      (i)Pr(2)C(6)H(3)) is reported as a highly efficient pre-catalyst for the
      hydroboration of aldehydes and ketones with pinacolborane.

PMID- 22473044
TI  - Consecutive iridium catalyzed C-C and C-H bond forming hydrogenations for the
      diastereo- and enantioselective synthesis of syn-3-fluoro-1-alcohols: C-H (2
      fluoro)allylation of primary alcohols.
AB  - Commercially available (2-fluoro)allyl chloride serves as an efficient allyl
      donor in highly enantioselective iridium catalyzed carbonyl (2-fluoro)allylations
      from the alcohol or aldehyde oxidation level via transfer hydrogenation.
      Diastereoselective Crabtree hydrogenation of the resulting homoallylic alcohols
      provides syn-3-fluoro-1-alcohols.

PMID- 22473042
TI  - The role and requirements of digestible dietary carbohydrates in infants and
      toddlers.
AB  - Digestible carbohydrates are one of the main sources of dietary energy in infancy
      and childhood and are essential for growth and development. The aim of this
      narrative review is to outline the intakes of digestible carbohydrates and their
      role in health and disease, including the development of food preferences, as
      well the consequences of excess carbohydrate. Key experts in these fields
      provided up-to-date reviews of the literature. A search of available information
      on dietary intakes of children below the age of 4 years was conducted from 1985
      up to 2010. Articles and reports including information about sugars and/or starch
      intakes were selected. A number of factors limit the ability to obtain an overall
      picture of carbohydrate intakes and food sources in this age group. These include
      small numbers of intake studies, differing approaches to analysing carbohydrate,
      a variety of terms used to describe sugars intakes and a dearth of information
      about starch intakes. Data suggest that sweet taste is preferred in infancy and
      later food choices. There are few established adverse consequences of high
      intakes of digestible carbohydrate for young children. The greatest evidence is
      for dental caries, although this is influenced by high intake frequency and poor
      oral hygiene. Evidence for detrimental effects on nutrient dilution, obesity,
      diabetes or cognition is limited. In infants, minimum carbohydrate (mainly
      lactose) intake should be 40% of total energy, gradually increasing to 55% energy
      by the age of 2 years.

PMID- 22473046
TI  - Contact activation of coagulation depends on the maximal lipophilic trigger
      concentration.
AB  - Contact activation of hemostasis is of great clinical importance. Intrinsic
      coagulation starts upon blood matrix change, resulting in activation of factor
      XII (F XII) to F XIIa and/or of prekallikrein to kallikrein. The intrinsic system
      is very complex. There are many reactions that can increase or decrease the
      generation of F Xa/thrombin. Currently, there are two main trigger types that
      activate the intrinsic system: (delta)-negatively charged molecules and
      lipophilic molecules. Recently, it was shown that the stimulation of thrombin
      generation by (delta)-negatively charged molecules depends on their maximal
      plasma concentration prior to plasma dilution. The questions arise whether this
      is also true for lipophilic triggers. Fifty-microliter frozen/thawed pooled
      normal platelet-poor citrated plasma (PNP) were supplemented with up to 5% (final
      concentration) hexane, followed by repetitive 1 + 1 dilutions on polystyrene U
      wells microtiter plates of high quality (Brand, Wertheim, Germany; article number
      781600). Immediately thereafter, the recalcified coagulation activity assay was
      started and the approximate 200% stimulatory concentrations (approx. SC200s) on
      intrinsic thrombin generation were determined, the 100% control being
      unsupplemented PNP. The higher the maximal concentration of hexane prior to
      dilution, the higher the approx. SC200. If the maximal hexane concentration prior
      to dilution was higher than 2%, PNP had an approx. SC200 of 0.1-0.2% (8-15
      mmol/l) hexane. At maximal hexane concentrations prior to dilution in the range
      of 0.1-1%, the approx. SC200 decreased 10-fold to about 0.01-0.02%. Up to about
      0.1% maximal hexane concentration prior to dilution the corresponding approx.
      SC200 of hexane on intrinsic thrombin generation was 0.003-0.01% (0.2-0.8
      mmol/l). Both main types of contact triggers - negatively charged or lipophilic
      molecules - have a peculiar behavior respective to maximal plasma
      concentration/thrombin generation: if the maximal plasma concentration of the
      trigger prior to plasma dilution is high, then the thrombin generating system
      needs rather high amounts of triggers to reach approx. SC200; and, if the maximal
      plasma concentration of the trigger prior to dilution is low, then thrombin is
      easily generated with a low approx. SC200. This means that the plasmatic F
      XII/prekallikrein/HMWK system could be inhibited by high plasma concentrations of
      any trigger and this inhibition cannot be reversed by plasma dilution. To study
      the action of drugs on the intrinsic system of plasma, plasma should be
      supplemented with the respective drug at maximal concentrations that are in the
      range of the maximal blood concentrations obtained in clinical medicine.

PMID- 22473047
TI  - The utility of thromboelastography in monitoring low molecular weight heparin
      therapy in the coronary care unit.
AB  - Low molecular weight heparins (LMWHs) are used for prevention and management of
      vascular thrombosis. In general, monitoring of anticoagulant activity is not
      required, however, certain populations may be susceptible to overdosing or
      underdosing. As anti-activated factor X(anti-Xa) activity testing is not readily
      available, it was our aim to investigate the usefulness of thromboelastography
      (TEG; Haemoscope Corporation, Skokie, Illinois, USA) for the assessment of
      coagulation in patients on LMWH. All patients admitted to the coronary care unit
      on therapeutic dose of enoxaparin were included (1 mg/kg twice daily). Blood
      samples were collected 4 h after the morning dose of enoxaparin once the
      participant had received at least three doses. When anti-Xa activity was
      classified as low (0-0.5), correct (0.5-1.0) or high (>1.0), the distribution of
      reaction time (R) and dose per kg showed little association with anti-Xa
      activity. The difference between mean R for the high anti-Xa group and the
      correct anti-Xa group was statistically nonsignificant using two-sample t-test (P
      = 0.26). A linear regression model showed no evidence of association between dose
      per kg and anti-Xa (P = 0.95). However, there was evidence of positive
      association between dose per kg and R (P = 0.011) wherein a 10% increase in dose
      per kg was associated with an increase in R of 2.7 (95% confidence interval 0.6
      4.7). There was no evidence of association between R and anti-Xa (P = 0.38). TEG
      was unable to be used to predict anti-Xa activity. However, TEG R was prolonged
      in more than 90% patients and correlated with dose of enoxaparin. As enoxaparin
      dose correlated poorly with anti-Xa activity, a more global test might be
      necessary to adjust dosing of LMWH in sick, hospitalized patients.

PMID- 22473048
TI  - Polymorphism G-308A in the promoter of the tumor necrosis factor-alpha gene and
      its association with the risk of venous thromboembolism.
AB  - The main abnormalities associated with the increased risk of venous thrombosis
      are the inherited deficiencies of antithrombin, protein C, protein S, the point
      mutations known as factor V Leiden and factor II G20210A. The association of
      other specific genes with thrombotic risk is less known. G-308A polymorphism in
      the promoter area of the gene coding for tumor necrosis factor alpha (TNF-alpha)
      is associated with an increased transcription activity of this gene, increased
      TNF-alpha production and subsequent predisposition to some illnesses. The aim of
      this work was to study the link between this polymorphism and predisposition to
      deep venous thrombosis (DVT). The research determined the frequency of the
      variant allele -308A in the gene for TNF-alpha in a group of 67 patients
      diagnosed with DVT and in a group of 62 healthy volunteers. We confirmed
      statistically significant link between the occurrence of the variant allele -308A
      and DVT (P = 0.02). This mutation was associated with a 2.64-fold greater risk of
      venous thrombosis, 95% confidence interval (1.19-5.87). When excluding
      heterozygous and homozygous carriers of the Leiden mutation from both groups, the
      difference between the occurrence of the variant allele -308A in the groups of
      ill and healthy individuals remained statistically significant (P = 0.04). The
      statistical significance was also confirmed after the exclusion of patients with
      mutation in the gene for prothrombin (P = 0.02). The results of this work imply
      possible association between the variant allele -308A and the development of DVT.

PMID- 22473049
TI  - A rare case of factor V inhibitor in a patient on amiodarone therapy.
AB  - Factor V inhibitor is in itself a rare entity. We are reporting a case of an
      elderly male who presented with symptoms of bleeding and was later found to have
      developed factor V inhibitors. He had been on amiodarone for atrial fibrillation
      and developed hemorrhagic manifestations due to factor V inhibitors within a few
      months of initiating amiodarone therapy. Most of the cases of factor V inhibitors
      reported in the literature were found to be associated with exposure to bovine
      coagulation factors. However, in our case there was no evidence of bovine
      thrombin use during surgery. Furthermore, bovine thrombin-associated factor V
      inhibitors commonly emerge within 1-2 weeks after exposure during surgery versus
      several months later in our patient. There was dramatic improvement in the
      coagulation profile 6 weeks after discontinuation of amiodarone and institution
      of steroids and cyclophosphamide. We propose the consideration of amiodarone as a
      contributing agent in inhibitor generation even though a spontaneous development
      of factor V inhibitor could not be ruled out.

PMID- 22473050
TI  - Do patients with haemophilia and von Willebrand disease with arterial
      hypertension have bleeding complications:  a German single centre cohort.
AB  - Arterial hypertension is very common and occurs often in patients with
      haemophilia A (HA) and von Willebrand disease (VWD) due to their increased life
      expectancy. Bleeding complications in haemophilia and von Willebrand patients
      with hypertension so far are not well evaluated. Even data regarding the use of
      antihypertensive treatment in these patients are lacking. That is why we want to
      establish a register of the patients regarding the bleeding complications under
      arterial hypertension. The prevalence of arterial hypertension in our patients'
      population (n = 258 of >18 years, 121 men, 137 women) was as follow: 190 patients
      had VWD 1, eight VWD 2A, one VWD 2B, five VWD 3, 39 haemophilia A (two severe,
      one moderate, 36 mild). All patients (n = 258) had arterial hypertension because
      this was our issue. Certainly, patients even had more coronary risk factors. One
      important risk factor was hyperlipoproteinemia (n = 111). Nicotine abuse was rare
      (nine patients, 3.4%). Adipositas (78 +/- 18 kg, range 37-164 kg, median BMI =
      23.2 kg/m(2)) as well as obstructive sleep apnoea (two patients) were not common.
      Regarding the cohort, 57 patients with bleeding disorder and hypertension
      suffered from coronary artery disease. No major bleeding or ischemic
      complications were observed. Obviously, patients with haemophilia and VWD with
      arterial hypertension do not have an increased risk of bleeding. Adequate
      treatment is necessary. International registers with a larger number of patients
      can be useful.

PMID- 22473051
TI  - Mean platelet volume is associated with culprit lesion severity and cardiac
      events in acute coronary syndromes without ST elevation.
AB  - We investigated the association of mean platelet volume (MPV) with culprit lesion
      severity and major cardiac outcomes (MCOs) in patients with acute coronary
      syndrome (ACS) with non-ST elevation (NSTE). This study included 344 patients
      with NSTE-ACS who had significant coronary stenosis at least 50%. They were
      divided into high MPV group (n = 109, upper tertile >9.9 fl) and low MPV group (n
      = 235, lower and mid tertile <= 9.9 fl) according to MPV values on admission.
      They were followed up for MCOs during 12 months. MCO consisted of the composite
      end-point of cardiac death, myocardial infarction (MI), recurrent angina or
      hospitalization. High MPV was independently associated with NSTE-MI [odds ratio
      (OR) 4.24, 95% confidence interval (CI) 2.52-7.15, P = 0.001] and severe culprit
      stenosis (>= 80%) (OR 4.05, 95% CI 2.39-6.83, P = 0.001). MPV of 9.9 fl was
      predictive of severe culprit stenosis with a sensitivity of 73% and specificity
      of 77% (P < 0.001). At 12 months, MCO rate was higher in high MPV group than low
      MPV group (39 vs. 26%; P = 0.016). This difference resulted from death (6.4 vs.
      2.1; P = 0.06) and recurrent angina (16.5 vs. 8.9%; P = 0.045). The MCO-free
      survival was worse in patients with high MPV than those with low MPV (61 vs. 74%;
      P = 0.01). In Cox regression analysis, high MPV remained an independent predictor
      of MCO (hazard ratio 1.52, 95% CI 1.01-2.29, P = 0.04) after adjusting for
      baseline characteristics. Elevated MPV was independently associated with NSTE-MI
      presentation and severity of culprit stenosis in NSTE-ACS patients. Moreover, MPV
      greater than 9.9 fl was predictive of a 12-month MCO.

PMID- 22473052
TI  - The relationship between mean platelet volume with metabolic syndrome in obese
      individuals.
AB  - The metabolic syndrome is closely associated with atherosclerotic risk factors
      and increased mortality. Mean platelet volume (MPV) is an indicator of platelet
      activation which also shows a close relationship with cardiovascular risk
      factors, such as diabetes mellitus, hypertension, hypercholesterolemia, obesity,
      metabolic syndrome. The aim of this study was to investigate the correlates of
      metabolic syndrome, its components and MPV adjusted for obesity in a large
      population study. A total of 2298 individuals with a mean age of 50 (age range 18
      92) were interviewed. Nine hundred and twenty obese participants, who had BMI 30
      kg/m2 or more, further evaluated for the presence of metabolic syndrome. Five
      hundred and thirteen [396 women (70.2%)] had metabolic syndrome and the rest 407
      individuals [324 women (79.6%)] served as the control group. The BMI, SBP, DBP,
      waist circumference, fasting plasma glucose, visceral fat, total cholesterol,
      high-density lipoprotein-cholesterol, and triglyceride was higher significantly
      in metabolic syndrome group (P = 0.002 for BMI and P < 0.001 for the others). No
      significant difference was observed between groups regarding low-density
      lipoprotein cholesterol, white blood cells, platelet counts, MPV, hematocrit and
      hemoglobin (P > 0.05 for all). The presence of metabolic syndrome and its
      components do not constitute a difference in MPV values in obese patients with a
      BMI 30 kg/m2 or more.

PMID- 22473055
TI  - Long-term effects of nucleus accumbens deep brain stimulation in treatment
      resistant depression: evidence for sustained efficacy.
AB  - Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated
      with antidepressant, anxiolytic, and procognitive effects in a small sample of
      patients suffering from treatment-resistant depression (TRD), followed over 1
      year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described
      in a group of 11 patients. Clinical effects, quality of life (QoL), cognition,
      and safety are reported. Eleven patients were stimulated with DBS bilateral to
      the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating
      Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale)
      QoL (SF-36), cognition and safety at baseline, 12 months (n=11), 24 months
      (n=10), and last follow-up (maximum 4 years, n=5). Analyses were performed in an
      intent-to-treat method with last observation carried forward, thus 11 patients
      contributed to each point in time. In all, 5 of 11 patients (45%) were classified
      as responders after 12 months and remained sustained responders without worsening
      of symptoms until last follow-up after 4 years. Both ratings of depression and
      anxiety were significantly reduced in the sample as a whole from first month of
      NAcc-DBS on. All patients improved in QoL measures. One non-responder committed
      suicide. No severe adverse events related to parameter change were reported.
      First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable
      antidepressant and anxiolytic effect and an amelioration of QoL in this small
      sample of patients suffering from TRD. None of the responders of first year
      relapsed during the observational period (up to 4 years).

PMID- 22473056
TI  - Aquaporin-4 deficiency impairs synaptic plasticity and associative fear memory in
      the lateral amygdala: involvement of downregulation of glutamate transporter-1
      expression.
AB  - Astrocytes are implicated in information processing, signal transmission, and
      regulation of synaptic plasticity. Aquaporin-4 (AQP4) is the major water channel
      in adult brain and is primarily expressed in astrocytes. A growing body of
      evidence indicates that AQP4 is a potential molecular target for the regulation
      of astrocytic function. However, little is known about the role of AQP4 in
      synaptic plasticity in the amygdala. Therefore, we evaluated long-term
      potentiation (LTP) in the lateral amygdala (LA) and associative fear memory of
      AQP4 knockout (KO) and wild-type mice. We found that AQP4 deficiency impaired LTP
      in the thalamo-LA pathway and associative fear memory. Furthermore, AQP4
      deficiency significantly downregulated glutamate transporter-1 (GLT-1) expression
      and selectively increased NMDA receptor (NMDAR)-mediated EPSCs in the LA.
      However, low concentration of NMDAR antagonist reversed the impairment of LTP in
      KO mice. Upregulating GLT-1 expression by chronic treatment with ceftriaxone also
      reversed the impairment of LTP and fear memory in KO mice. These findings imply a
      role for AQP4 in synaptic plasticity and associative fear memory in the amygdala
      by regulating GLT-1 expression.

PMID- 22473057
TI  - Reduced in vivo ocular surface toxicity with polyquad-preserved travoprost versus
      benzalkonium-preserved travoprost or latanoprost ophthalmic solutions.
AB  - The study used a validated acute in vivo model to compare a new formulation of
      travoprost 0.004% ophthalmic solution(travoprost PQ), preserved with
      polyquaternium-1 (PQ), with commercially available formulations of benzalkonium
      chloride(BAK)-preserved travoprost 0.004% ophthalmic solution(travoprost BAK) and
      BAK-preserved latanoprost 0.005%ophthalmic solution (latanoprost BAK). Adult male
      New Zealand albino rabbits (n = 36) were randomly divided into 6 groups.
      Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost
      BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5
      min intervals.The ocular surface reactions were investigated at hour 4 and day 1
      using slitlamp examination; in vivo confocal microscopy (IVCM) for cornea, limbus
      and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression
      cytology and standard immunohistology in cryosections for detecting CD45+
      infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not
      induce obvious irritation by clinical observation, changes in microstructures of
      the whole ocular surface as measured by IVCM analysis,inflammatory infiltration
      or cell damage as measured by impression cytology, altered levels of goblet cell
      counts or numerous CD45+ cells in the cornea. In contrast, all BAK-containing
      products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in
      the ocular surface microstructure,significant total ocular surface toxicity
      scores,damaged epithelial cells, inflammatory cell infiltration and decreased
      goblet cell density. Travoprost PQ did not elicitocular surface toxicity when
      administered to rabbit eyes.These results suggest a greater safety advantage for
      the ocular surface of patients receiving chronic glaucoma treatment with PQ
      preserved drugs.

PMID- 22473058
TI  - Risk factors in patients with hereditary gallstones in Chinese pedigrees.
AB  - OBJECTIVE: We aimed to define the risk factors and to evaluate the impact of
      family background on the prevalence of gallstones in China. SUBJECTS AND METHODS:
      Thirty-eight gallstone pedigrees were collected and a case-control study was
      conducted. This study consisted of 272 first-degree relatives and 201 non-first
      degree relatives of index patients. The participants completed a questionnaire
      and underwent physical and ultrasonographic examinations. The risk factors
      examined included age, sex, body mass index (BMI), smoking status, alcohol
      consumption, pregnancy, fat content in dietary meat, history of gastrointestinal
      surgery, hypertension, hyperlipidemia, fatty liver, coronary heart disease and
      diabetes. RESULTS: The prevalence of gallstones in first-degree and non-first
      degree relatives of index patients was 38.2 and 10.9%, respectively. Age,
      pregnancy and BMI significantly differed between cases and controls (p < 0.05).
      The relative risks were: consumption of meat with a high fat content 1.4 (95% CI
      1.1-1.8); hyperlipidemia 2.4 (95% CI 1.3-4.6); diabetes 1.9 (95% CI 1.1-3.2);
      fatty liver 4.9 (95% CI 1.0-24); coronary heart disease 2.5 (95% CI 1.7-3.9).
      CONCLUSION: Data showed that age, overweight, more consumption of high-fat food,
      high frequency of pregnancy, fatty liver, hyperlipidemia, coronary heart disease
      and diabetes could increase the risk of gallstones in the first-degree relatives
      of index patients.

PMID- 22473059
TI  - Single-molecule studies of DNA transcription using atomic force microscopy.
AB  - Atomic force microscopy (AFM) can detect single biomacromolecules with a high
      signal-to-noise ratio on atomically flat biocompatible support surfaces, such as
      mica. Contrast arises from the innate forces and therefore AFM does not require
      imaging contrast agents, leading to sample preparation that is relatively
      straightforward. The ability of AFM to operate in hydrated environments,
      including humid air and aqueous buffers, allows structure and function of
      biological and biomolecular systems to be retained. These traits of the AFM are
      ensuring that it is being increasingly used to study deoxyribonucleic acid (DNA)
      structure and DNA-protein interactions down to the secondary structure level.
      This report focuses in particular on reviewing the applications of AFM to the
      study of DNA transcription in reductionist single-molecule bottom-up approaches.
      The technique has allowed new insights into the interactions between ribonucleic
      acid (RNA) polymerase to be gained and enabled quantification of some aspects of
      the transcription process, such as promoter location, DNA wrapping and
      elongation. More recently, the trend is towards studying the interactions of more
      than one enzyme operating on a single DNA template. These methods begin to reveal
      the mechanics of gene expression at the single-molecule level and will enable us
      to gain greater understanding of how the genome is transcribed and translated
      into the proteome.

PMID- 22473060
TI  - Talk of frustration in the narratives of people with chronic pain.
AB  - OBJECTIVES: To improve understanding of the sources of frustration for people
      with chronic pain and consider the potential influence of frustration on the
      chronic pain experience and relationships with health professionals. METHODS:
      Qualitative in-depth interviews with a diverse, maximum variation sample of 46
      participants with chronic pain, 30 of whom talked about frustration. Analysis
      paid close attention to how people talked about their frustration as well as what
      they said. RESULTS: Frustration is a multi-faceted emotion and its effects are
      cumulative. Sources of frustration include interference with everyday activities,
      the interruption of life goals and roles and the unpredictability of pain; here
      we focus on the frustrations associated with the invisibility of chronic pain and
      the perceived limitations of diagnosis and pain management (both related to the
      perceived legitimacy of the condition). Several of the participants who had lived
      with chronic pain for many years described overcoming, or managing, their
      frustrations. DISCUSSION: If patients think that their pain is not being believed
      this is clearly a barrier to an effective consultation. Communication with
      chronic pain patients may improve if the frustration of living with an invisible,
      debilitating condition that is hard to diagnose and treat is explicitly (and
      perhaps repeatedly) acknowledged by the health professional.

PMID- 22473062
TI  - A preliminary study of platelet activation after embolization of marrow contents.
AB  - OBJECTIVES: Intravasation of bone marrow contents into venous circulation and
      pulmonary embolization after intramedullary nailing may be coupled with the
      activation of coagulation and fibrinolytic cascades. The objective of this study
      was to assess hemostatic response to pulmonary extravasated marrow contents. We
      hypothesize that activation of platelet activity and the coagulation cascade may
      occur after embolization of marrow contents in an experimental animal model of
      intramedullary nailing. METHODS: Fifteen New Zealand white male rabbits were
      randomly assigned to control or fat embolism (FE) groups. In the FE group (n =
      8), femurs were surgically instrumented with retrograde intramedullary nails and
      pressurized with bone cement. In the control group (n = 7), a sham knee incision
      was made that was immediately closed without drilling, reaming, or
      pressurization. Fibrinogen, D-dimer latex screen assay, 1 stage prothrombin time,
      and activated partial thromboplastin time were analyzed. RESULTS: As the main
      platelet activation indicators, the marker Annexin-V percent binding increased in
      the FE group at 2 hours (P = 0.04) and 4 hours (P = 0.04), and the marker CD62P
      percent expression increased in the FE group at 2 hours (P = 0.04). CONCLUSIONS:
      This preliminary study showed that pressurization of marrow and intravasation of
      fat and marrow products cause activation of platelets and the coagulation
      cascade, with or without tissue trauma. This may be relevant to the treatment of
      multiply injured patients with prior respiratory and coagulation abnormalities. A
      future larger study may be needed.

PMID- 22473061
TI  - FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY.
AB  - Gene therapy has great potential to bring tremendous changes in treatment of
      various diseases and disorders. However, one of the impediments to successful
      gene therapy is the inefficient delivery of genes to target tissues and the
      inability to monitor delivery of genes and therapeutic responses at the targeted
      site. The emergence of molecular imaging strategies has been pivotal in
      optimizing gene therapy; since it can allow us to evaluate the effectiveness of
      gene delivery noninvasively and spatiotemporally. Due to the unique
      physiochemical properties of nanomaterials, numerous functional nanoparticles
      show promise in accomplishing gene delivery with the necessary feature of
      visualizing the delivery. In this review, recent developments of nanoparticles
      for molecular imaging guided gene delivery are summarized.

PMID- 22473063
TI  - A new fracture model for "terrible triad" injuries of the elbow:  influence of
      forearm rotation on injury patterns.
AB  - OBJECTIVE: The purpose of this study was to evaluate the influence of forearm
      rotation on failure patterns of the elbow under axial loads. METHODS: Fourteen
      upper extremities were resected mid-humerus and mounted on a custom apparatus,
      which allowed rotation of the ulna, radius, and humerus about a fixed wrist while
      loading in axial compression. Seven specimens were loaded to failure with the
      forearm in pronation and 7 in supination. RESULTS: Six of the 7 elbows axially
      loaded in pronation resulted in fractures of the radial head and coronoid with
      posterior dislocation (terrible triad). Six of the 7 elbows loaded in supination
      dislocated without fracture. One of the 7 elbows tested in supination had a
      terrible triad-type elbow injury. Five of the 6 specimens with ulna external
      rotation had damage to the lateral ligaments; all 8 specimens with internal
      rotation had damage to the medial ligaments. There were no significant
      differences in biomechanical parameters between pronation and supination.
      CONCLUSIONS: The forearm position during axial load was the primary determinant
      of fracture-dislocation pattern. When the forearm was pronated, a terrible triad
      injury pattern most often occurred. When the forearm was supinated, a dislocation
      without fracture most often occurred. In both forearm rotation positions, when
      the ulna internally rotated during failure, the medial structures were the first
      to be disrupted. When the ulna externally rotated, the lateral structures were
      the first to be disrupted. Understanding the pathomechanics of elbow dislocation
      may improve diagnosis and treatment of these injuries.

PMID- 22473064
TI  - Distal locking of femoral nails:  evaluation of a new radiation-independent
      targeting system.
AB  - OBJECTIVES: The purpose of this study was to assess the effectiveness of a novel
      radiation-independent aiming device for distal locking of intramedullary nails in
      a human cadaver model. METHODS: A new targeting system was used in 25 intact
      human cadaver femora for the distal locking procedure after insertion of an
      intramedullary nail. The number of successful screw placements and the time
      needed for this locking procedure were recorded. The accuracy of the aiming
      process was evaluated by computed tomography. RESULTS: The duration of the distal
      locking process was 8.0 +/- 1.8 minutes (mean +/- SD; range, 4-11 minutes). None
      of the screw placements required fluoroscopic guidance. Computed tomography
      revealed high accuracy of the locking process. The incidence angle (alpha) of the
      locking screws through the distal locking holes of the nail was 86.8 degrees  +/-
      5.0 degrees  (mean +/- SD; range, 80 degrees -96 degrees ). Targeting failed in 1
      static locking screw because of a material defect in the drilling sleeve.
      CONCLUSIONS: This cadaver study indicated that an aiming arm-based targeting
      device is highly reliable and accurate. The promising results suggest that it
      will help to decrease radiation exposure compared with the traditional "free-hand
      technique."

PMID- 22473065
TI  - Time-dependent effects of chlorhexidine soaks on grossly contaminated bone.
AB  - OBJECTIVE: The purpose of this study was to quantify the reduction in the
      bacterial burden of grossly contaminated bone segments using different
      chlorhexidine (CHL) solutions. We hypothesized that 4% CHL would be the most
      efficient decontaminate. METHODS: Fifty-four bone segments were harvested from
      fresh-frozen porcine legs. Each specimen was dropped onto a Mueller-Hinton medium
      that was inoculated with Staphylococcus aureus (lux). These genetically
      engineered bacteria emit photons in proportion to their number, allowing for
      quantification. The segments were retrieved after 5 seconds of exposure. Baseline
      imaging provided the initial bacterial load. An equal number of specimens were
      soaked in normal saline (NS), 2%CHL, or 4%CHL. Specimen reimaging was completed
      at the 5-, 10-, 20-, 30-, and 60-minute marks. RESULTS: The average bacterial
      count on the bone segments were 2.18 * 10(7) for NS, 2.31 * 10(7) for 2%CHL, and
      2.00 * 10(7) for 4%CHL. The percent reduction in bacterial counts at the 5-, 10-,
      20-, 30-, and 60-minute marks were NS: 0%, 0%, 0%, 29.84%, 72.23%; 2%CHL: 93.09%,
      98.16%, 99.21%, 99.63%, 99.81%; 4%CHL: 94.32%, 97.60%, 99.25%, 99.63%, 99.82%. At
      all time intervals, there was a significant difference between the 2%CHL and
      4%CHL groups compared with the NS group (P < 0.0001) and no difference between
      the 2%CHL and 4%CHL groups. CONCLUSIONS: This study provides new data supporting
      the use of CHL to decontaminate grossly soiled bone segments. To maximize
      efficiency and decrease potential untoward effects, the authors recommend 20
      minute soaks using 2% CHL for contaminated bone segments.

PMID- 22473067
TI  - Is surgical fixation for stress-positive unstable ankle fractures cost effective?
      Results of a multicenter randomized control trial.
AB  - OBJECTIVES: A recent multicenter randomized control trial demonstrated similar
      quality of life at 1 year after open reduction and internal fixation (ORIF)
      compared with nonoperative treatment for stress-positive unstable isolated
      lateral malleolar fractures. We sought to determine the cost-effectiveness of
      ORIF compared with nonoperative management of these isolated lateral malleolar
      fractures. DESIGN: Cost-utility analysis using decision tree and Markov modeling
      based on data from a prospective randomized control trial and previously
      published literature. A single-payer perspective with 1-year and lifetime time
      horizons was adopted. SETTING: Clinical trial data from 6 Canadian level I trauma
      hospitals. INTERVENTION: Lateral malleolus ORIF versus nonoperative treatment.
      MAIN OUTCOME MEASUREMENTS: Incremental cost-effectiveness ratio (ICER). RESULTS:
      The base case 1-year ICER of the ORIF treatment was $205,090 per quality-adjusted
      life year gained, favoring nonoperative treatment. For the lifetime time horizon,
      ORIF becomes the preferred treatment with an ICER of $16,404 per quality-adjusted
      life year gained. This conclusion is stable provided ORIF lowers the lifetime
      incidence of ankle arthrosis by >3% compared with nonoperative treatment.
      Probabilistic sensitivity analysis demonstrated that 33% of model simulations
      favored ORIF in the 1-year time horizon and 65% of simulations in the lifetime
      time horizon. CONCLUSIONS: From a single-payer governmental perspective, ORIF
      does not seem to be cost effective in the 1-year time horizon; however, if
      operative fixation decreases the lifetime incidence of posttraumatic ankle
      arthrosis by >3%, then ORIF becomes the economically preferred treatment. LEVEL
      OF EVIDENCE: Economic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 22473068
TI  - The safe zone for external fixator pins in the femur.
AB  - OBJECTIVE: To define the anatomic "safe zone" for placement of external fixator
      half pins into the anterior and lateral femur. METHODS: In 20 fresh-frozen
      hemipelvis specimens, the femoral nerve and all branches crossing the femur were
      dissected out to their final muscular locations. The location where the nerves
      crossed the anterior femur was measured from the anterior superior iliac spine
      and inferior margin of the lesser trochanter. The knee joint was then opened, and
      the distance from the superior reflection of the suprapatellar pouch to the last
      branch of the femoral nerve crossing the anterior femur was measured, defining
      the safe zone for anterior pin placement. RESULTS: The last branch of the femoral
      nerve crossed at an average distance from the anterior superior iliac spine of
      174 +/- 43 mm (range, 95-248 mm) and from the lesser trochanter at a distance of
      58 +/- 36 mm (range, 0-136 mm). The average distance from the proximal pole of
      the patella to the superior reflection of the suprapatellar pouch was 46.3 +/-
      13.1 mm (range, 20-74 mm). Using the linear distance between the last crossing
      femoral nerve branch and the superior reflection of the pouch, the average safe
      zone measured 199 +/- 39.8 mm (range, 124-268 mm). The safe zone correlated with
      thigh length (r = 0.48, P = 0.03). All nerve branches terminated at their
      muscular origins without crossing lateral to a line from the anterior greater
      trochanter to the anterior aspect of the lateral femoral condyle. CONCLUSIONS:
      The safe zone for anterior external fixator half pin placement into the femur is
      on average 20 cm in length and can be as narrow as 12 cm. Anterior pins should
      begin 7.5 cm above the superior pole of the patella to avoid inadvertent knee
      joint penetration. Because the entire lateral femur is safely available for half
      pin placement, including distally, we recommend the use of alternative frame
      constructs with either anterolateral or lateral pins given the limitations and
      risks of anterior pin placement.

PMID- 22473071
TI  - Iridium catalysed chemoselective alkylation of 2'-aminoacetophenone with primary
      benzyl type alcohols under microwave conditions.
AB  - 2'-Aminoacetophenone was chemoselectively alkylated with a range of substituted
      benzyl, heteroaryl alcohols to afford either the corresponding C- or N- alkylated
      products in good yield.

PMID- 22473072
TI  - Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF
      dependent mechanism.
AB  - BACKGROUND/OBJECTIVES: Cilostazol has been found to be effective for the
      treatment of intermittent claudication (IC). This compound has several beneficial
      effects on platelet aggregation, serum lipids and endothelial cells, but how
      these might relate to improvements in walking is not entirely understood. The aim
      of this work was to investigate the effects of cilostazol on angiogenic response
      in a murine model of peripheral ischemia and to clarify the underlying molecular
      mechanisms of that response. METHODS: We studied ischemia-induced
      neovascularization in the ischemic hindlimb of cilostazol-treated and untreated
      control mice. RESULTS: We found that the perfusion recovery was significantly
      improved in treated compared with control mice. Interestingly, there was a higher
      level of circulating endothelial progenitor cells (EPCs) in mice treated with
      cilostazol than in untreated mice. Furthermore, cilostazol administration
      resulted in upregulation of granulocyte colony-stimulating factor (G-CSF) and
      vascular endothelial growth factor (VEGF) in the ischemic muscle of treated mice.
      Finally, inhibiting VEGF activity significantly reduced cilostazol-induced
      angiogenesis. CONCLUSIONS: The results of this study show that cilostazol
      administration enhances collateral blood flow in the ischemic hindlimbs of mice
      through a VEGF-dependent mechanism. These data may help to explain the beneficial
      effects that this drug has on patients with peripheral arterial disease (PAD) and
      IC.

PMID- 22473073
TI  - Effects of gum arabic (Acacia senegal) on renal function in diabetic mice.
AB  - BACKGROUND/AIMS: Gum arabic (GA) is a Ca(2+)-, Mg(2+)- and K(+)-rich dietary
      fiber used for the treatment of patients with chronic kidney disease in Middle
      Eastern countries. In healthy mice, GA treatment increases creatinine clearance,
      renal ADH excretion, as well as intestinal and renal excretion of Mg(2+) and
      Ca(2+). GA decreases plasma Pi concentration, urinary Pi and Na(+) excretion. The
      present study explored the effects of GA on renal function in diabetic mice.
      METHODS: Metabolic cage experiments were performed on Akita mice (akita(+/-)),
      which spontaneously develop insulin deficiency and thus hyperglycemia. Plasma and
      urinary concentrations of Na(+), K(+) and Ca(2+) were measured by flame
      photometry (AFM 5051, Eppendorf, Germany), creatinine by the Jaffe method,
      phosphate photometrically, urea by an enzymatic method, glucose utilizing a
      glucometer and an enzymatic kit, aldosterone using an RIA, urinary albumin
      fluorometrically, and blood pressure by the tail-cuff method. RESULTS: GA (10% in
      drinking water) significantly increased urinary excretion of Ca(2+) and
      significantly decreased plasma phosphate and urea concentrations, urinary flow
      rate, urinary Na(+), phosphate and glucose excretion, blood pressure and
      proteinuria. CONCLUSIONS: GA treatment decreases blood pressure and proteinuria
      in diabetic mice and may thus prove beneficial in diabetic nephropathy.

PMID- 22473074
TI  - Large-scale identification of selenium metabolites by online size-exclusion
      reversed phase liquid chromatography with combined inductively coupled plasma
      (ICP-MS) and electrospray ionization linear trap-Orbitrap mass spectrometry (ESI
      MS(n)).
AB  - A method was developed for the comprehensive cartography of the selenium
      metabolites synthesized in the process of conversion of selenite [Se(iv)] into
      organic compounds and enrichment of yeast with selenium. The number of compounds
      detected was considerably increased (49) owing to the optimization of the
      fractionation procedure and the use of UPLC. The increased purity of the minor
      selenoorganic amino acids and oligopeptides allowed successful on-line de-novo
      identification based on the exact mass (<1 ppm) and fragmentation (MS(2)/MS(3))
      mass spectra obtained with high resolution and high mass accuracy. The quality of
      mass spectra allowed the re-interpretation of previously reported structures of
      some selenium species.

PMID- 22473075
TI  - MRI versus bone scintigraphy. Evaluation for diagnosis and grading of stress
      injuries.
AB  - AIM: This study was set up to determine the value of magnetic resonance imaging
      (MRI) and bone scintigraphy (BS) for the diagnosis of stress injuries in
      athletes, and furthermore to assess reliability and prediction of healing time.
      PATIENTS, METHODS: Imaging data was analyzed retrospectively from 28 athletes who
      had received MRI and BS examinations for suspected stress injuries. MRI- and BS
      data were rated by three specialists each in a blinded read, using a 5-point
      score (i.e. 0-4: inconspicuous to high-grade stress fracture). An
      interdisciplinary expert truth-panel set the reference standard. Standard
      statistical parameters, Fleiss' kappa (kappa), and group comparisons were
      calculated. RESULTS: The sensitivity, specificity, accuracy, positive predictive
      value (PPV), and negative predictive value (NPV) for detection of stress injuries
      were 71.4%, 85.7%, 78.6%, 83.3% and, 75.0%, for MRI and 92.9%, 73.8%, 83.3%,
      78.0% and, 91.2% for BS, respectively. Interobserver reliability for the
      diagnosis of a stress injury was kappa = 0.9 for BS and kappa = 0.85 for MRI.
      Mean healing times of mild (grades 1 and 2) and severe (grades 3 and 4) stress
      injuries were 88 days (d) versus 142d for BS and 57d versus 116d for MRI. No
      significant difference in healing time could be shown. CONCLUSIONS: MRI and BS
      reliably detect stress injuries. MRI is to be recommended as the primary imaging
      modality due to its potential for assessment of differential diagnoses and the
      lack of radiation exposure, the value of BS lies in the exclusion of stress
      fractures after inconclusive MRI examinations.

PMID- 22473076
TI  - Coronary artery disease: IL-6 signaling linked with CHD.

PMID- 22473082
TI  - Nitrogen-doped coatings on carbon nanotubes and their stabilizing effect on Pt
      nanoparticles.
AB  - A homogeneous coating of nitrogen-doped carbon on carbon nanotubes is performed
      using ionic liquids. The N-doped material is employed as a support for
      nanoparticles. Electrochemical degradation behavior is monitored in situ and
      compared to an unmodified material. The strongly enhanced stability is explained
      on the basis of a Pt-nitrogen interaction.

PMID- 22473079
TI  - Stress and cardiovascular disease.
AB  - The physiological reaction to psychological stress, involving the hypothalamic
      pituitary-adrenocortical and sympatho-adrenomedullary axes, is well
      characterized, but its link to cardiovascular disease risk is not well
      understood. Epidemiological data show that chronic stress predicts the occurrence
      of coronary heart disease (CHD). Employees who experience work-related stress and
      individuals who are socially isolated or lonely have an increased risk of a first
      CHD event. In addition, short-term emotional stress can act as a trigger of
      cardiac events among individuals with advanced atherosclerosis. A stress-specific
      coronary syndrome, known as transient left ventricular apical ballooning
      cardiomyopathy or stress (Takotsubo) cardiomyopathy, also exists. Among patients
      with CHD, acute psychological stress has been shown to induce transient
      myocardial ischemia and long-term stress can increase the risk of recurrent CHD
      events and mortality. Applications of the 'stress concept' (the understanding of
      stress as a risk factor and the use of stress management) in the clinical
      settings have been relatively limited, although the importance of stress
      management is highlighted in European guidelines for cardiovascular disease
      prevention.

PMID- 22473084
TI  - Neglected, developmental hip dislocation treated with external iliofemoral
      distraction, open reduction, and pelvic osteotomy.
AB  - Between 1995 and 2003, we operated upon 18 children with 20 hips involved, aged 5
      11 years (average: 7.5 years) suffering from an inveterate high developmental
      dislocation of the hip joint. An average follow-up period of our middle-term
      study was 51 months (range: 34-96 months). A two-staged management was applied.
      First, femoral head was lowered back to the level of acetabulum with an external
      fixator or a distractor device. The second stage involved open reduction combined
      with pelvic osteotomy and, in four cases with femoral derotation osteotomy. We
      noted two cases of avascular necrosis. Equal limb length was achieved in 15
      cases. There were two cases of 0.5-cm length discrepancy, two cases of 1-cm
      length inequalities, and one case of 5-cm limb shortening. We endorse this method
      in neglected cases of previously untreated unilateral high developmental hip
      dislocations in children aged 8-10 years. It results in a usable hip joint
      without the need of femoral shaft shortening and facilitates future joint
      replacement.

PMID- 22473085
TI  - Comment on 'Femoral neuropraxia after vaccination in a 3-month-old infant:  a
      case report'.

PMID- 22473083
TI  - Differences in cardiovascular risk factors and clinical outcomes between Western
      European and Southeast Asian patients treated with the Genous Bio-engineered R
      stent:  an e-HEALING worldwide registry substudy.
AB  - OBJECTIVE: Percutaneous coronary interventions (PCIs) are increasingly being
      performed worldwide to treat patients with coronary artery disease. However,
      studies on the influence of ethnicity on clinical outcomes after PCI are scarce.
      In our current analysis, we evaluate the differences in baseline clinical,
      angiographic and procedural characteristics, and 12-month clinical outcomes in
      patients undergoing nonurgent PCI in Western Europe and in Asia. METHODS: We
      analyzed all patients enrolled in the worldwide e-HEALING (electronic Healthy
      Endothelial Accelerated Lining Inhibits Neointimal Growth) registry living in
      Western Europe and Asia. All patients were treated with at least one endothelial
      progenitor cell capturing stent. The main study outcome was target vessel failure
      at the 12-month follow-up, defined as the composite of cardiac death or
      myocardial infarction and target vessel revascularization. RESULTS: A total of
      3504 patients, 2873 living in Western Europe and 731 living in Asia, were
      assessed in the current analysis. Almost all of the baseline clinical and
      angiographic characteristics differed significantly between both populations.
      Target vessel failure at the 12-month follow-up occurred in 11.4% of the Western
      Europe patients and in 5.6% of the Asian patients (P<0.01). CONCLUSION: We
      conclude that differences exist in the baseline, angiographic, and procedural
      characteristics between Western European and Asian patients undergoing nonurgent
      PCI. In addition, the 1-year clinical outcomes differ significantly after PCI
      between Western European and Asian patients. Our results indicate that reports
      from studies performed worldwide should include both overall and regional
      subgroup outcomes.

PMID- 22473086
TI  - The self-orientation of mammalian cells in optical tweezers--the importance of
      the nucleus.
AB  - Here we present the first evidence showing that eukaryotic cells can be stably
      trapped in a single focused Gaussian beam with an orientation that is defined by
      the nucleus. A mammalian eukaryotic cell (in suspension) is trapped and is re
      oriented in the focus of a linearly polarized Gaussian beam with a waist of
      dimension smaller than the radius of the nucleus. The cell reaches a position
      relative to the focus that is dictated by the nucleus and nuclear components. Our
      studies illustrate that the force exerted by the optical tweezers at locations
      within the cell can be predicted theoretically; the data obtained in this way is
      consistent with the experimental observations.

PMID- 22473087
TI  - Correlation between imatinib trough concentration and efficacy in Chinese chronic
      myelocytic leukemia patients.
AB  - BACKGROUND: Trough imatinib plasma concentration, intracellular drug levels and
      expression of drug transporters can be indicative of clinical responses in
      chronic myelocytic leukemia (CML) patients receiving imatinib. We aimed to
      determine plasma imatinib concentration, intracellular imatinib concentration,
      human organic cation transporter 1 (hOCT1) and adenosine triphosphate-binding
      cassette subfamily B member 1 (ABCB1) mRNA expression in bone marrow cells of CML
      patients in order to evaluate the potential usefulness of these measures as
      markers of imatinib efficacy and understand their clinical relationships.
      METHODS: Eighty-four CML patients receiving imatinib treatment were included in
      this study. Imatinib trough concentration was determined by high-performance
      liquid chromatography-tandem mass spectrometry. Real-time quantitative PCR with a
      TaqMan probe was used to assess hOCT1 and ABCB1 mRNA expression in bone marrow
      cells. All patients were divided into the major molecular response (MMR),
      complete cytogenetic response (CCyR), partial cytogenetic response (PCyR) or drug
      resistant groups according to their response. RESULTS: The plasma imatinib trough
      concentration was significantly higher in the MMR group than in the PCyR (p =
      0.002) or drug-resistant groups (p = 0.011). The plasma imatinib trough
      concentration was also significantly higher in the CCyR group than in the PCyR
      group (p = 0.027). There were no significant differences between the CCyR and MMR
      groups with regard to the plasma imatinib trough concentration (p = 0.136). The
      intracellular imatinib concentration in bone marrow cells was significantly
      higher in the CCyR group compared to the drug-resistant or PCyR groups (p =
      0.013). The hOCT1 mRNA expression in bone marrow cells was significantly higher
      in the CCyR group than in the drug-resistant or PCyR groups (p = 0.036). The
      ABCB1 mRNA expression in bone marrow cells was significantly higher in the drug
      resistant group than in the CCyR or PCyR groups (p = 0.013). Plasma imatinib
      trough concentration was positively correlated with alpha(1)-acid glycoprotein (r
      = 0.443, p < 0.001) or dose (r = 0.422, p < 0.001). CONCLUSIONS: Clinical
      responses in CML patients are correlated with both the plasma trough
      concentrations and intracellular levels of imatinib.

PMID- 22473088
TI  - The phenotype associated with a large deletion on MECP2.
AB  - Multiplex ligation-dependent Probe Amplification (MLPA) has become available for
      the detection of a large deletion on the MECP2 gene allowing genetic confirmation
      of previously unconfirmed cases of clinical Rett syndrome. This study describes
      the phenotype of those with a large deletion and compares with those with other
      pathogenic MECP2 mutations. Individuals were ascertained from the Australian Rett
      Syndrome and InterRett databases with data sourced from family and clinician
      questionnaires, and two case studies were constructed from the longitudinal
      Australian data. Regression and survival analysis were used to compare severity
      and age of onset of symptoms in those with and without a large deletion. Data
      were available for 974 individuals including 51 with a large deletion and ages
      ranged from 1 year 4 months to 49 years (median 9 years). Those with a large
      deletion were more severely affected than those with other mutation types.
      Specifically, individuals with large deletions were less likely to have learned
      to walk (OR 0.42, 95% CI: 0.22-0.79, P=0.007) and to be currently walking (OR
      0.53, 95% CI: 0.26-1.10, P=0.089), and were at higher odds of being in the most
      severe category of gross motor function (OR 1.84, 95% CI: 0.98-3.48, P=0.057) and
      epilepsy (OR 2.72, 95% CI: 1.38-5.37, P=0.004). They also developed epilepsy,
      scoliosis, hand stereotypies and abnormal breathing patterns at an earlier age.
      We have described the disorder profile associated with a large deletion from the
      largest sample to date and have found that the phenotype is severe with motor
      skills particularly affected.

PMID- 22473089
TI  - Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes.
AB  - Genetic factors underlying trait neuroticism, reflecting a tendency towards
      negative affective states, may overlap genetic susceptibility for anxiety
      disorders and help explain the extensive comorbidity amongst internalizing
      disorders. Genome-wide linkage (GWL) data from several studies of neuroticism and
      anxiety disorders have been published, providing an opportunity to test such
      hypotheses and identify genomic regions that harbor genes common to these
      phenotypes. In all, 11 independent GWL studies of either neuroticism (n=8) or
      anxiety disorders (n=3) were collected, which comprised of 5341 families with 15
      529 individuals. The rank-based genome scan meta-analysis (GSMA) approach was
      used to analyze each trait separately and combined, and global correlations
      between results were examined. False discovery rate (FDR) analysis was performed
      to test for enrichment of significant effects. Using 10 cM intervals, bins
      nominally significant for both GSMA statistics, P(SR) and P(OR), were found on
      chromosomes 9, 11, 12, and 14 for neuroticism and on chromosomes 1, 5, 15, and 16
      for anxiety disorders. Genome-wide, the results for the two phenotypes were
      significantly correlated, and a combined analysis identified additional nominally
      significant bins. Although none reached genome-wide significance, an excess of
      significant P(SR)P-values were observed, with 12 bins falling under a FDR
      threshold of 0.50. As demonstrated by our identification of multiple, consistent
      signals across the genome, meta-analytically combining existing GWL data is a
      valuable approach to narrowing down regions relevant for anxiety-related
      phenotypes. This may prove useful for prioritizing emerging genome-wide
      association data for anxiety disorders.

PMID- 22473090
TI  - PDGFRa mutations in humans with isolated cleft palate.
AB  - Isolated cleft palate (CP) is common in humans and has complex genetic
      etiologies. Many genes have been found to contribute to CP, but the full spectrum
      of genes remains unknown. PCR-sequencing of the entire coding regions and the 3'
      untranslated region (UTR) of the platelet-derived growth factor receptor alpha
      (PDGFRa) and the microRNA (miR), miR-140 identified seven novel single base-pair
      substitutions in the PDGFRa in 9/102 patients with CP (8.8%), compared with 5/500
      ethnic-matched unaffected controls (1%) (the two-tailed P-value<0.0001). Of these
      seven, four were missense mutations in the coding regions and three in the 3'UTR.
      Frequencies of four changes (three in coding, one in 3'UTR) were statistically
      different from those of controls (P-value<0.05). The c.*34G>A was identified in
      1/102 cases and 0/500 controls. This position is conserved in primates and
      located 10 bp away from a predicted binding site for the miR-140. Luciferase
      assay revealed that, in the presence of miR-140, the c.*34G>A significantly
      repressed luciferase activity compared with that of the wild type, suggesting
      functional significance of this variant. This is the first study providing
      evidence supporting a role of PDGFRa in human CP.

PMID- 22473091
TI  - Van Maldergem syndrome: further characterisation and evidence for neuronal
      migration abnormalities and autosomal recessive inheritance.
AB  - We present six patients from five unrelated families with a condition originally
      described by Van Maldergem et al and provide follow-up studies of the original
      patient. The phenotype comprises a distinctive facial appearance that includes
      blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the
      external auditory meatus, intellectual disability, digital contractures and
      skeletal anomalies together with subependymal and subcortical neuronal
      heterotopia. Affected patients typically have neonatal hypotonia, chronic feeding
      difficulties and respiratory problems. In our cohort, we have observed one
      instance of sibling recurrence and parental consanguinity in three of the
      families, indicating that autosomal recessive inheritance is likely.

PMID- 22473092
TI  - An in vivo highly antitumor-active tetrazolato-bridged dinuclear platinum(II)
      complex largely circumvents in vitro cisplatin resistance: two linkage isomers
      yield the same product upon reaction with 9-ethylguanine but exhibit different
      cytotoxic profiles.
AB  - Cytotoxicity assays of azolato-bridged dinuclear Pt(II) complexes, [{cis
      Pt(NH(3))(2)}(2)(MU-OH)(MU-azolato)](2+), where the azolato was pyrazolato (1),
      1,2,3-triazolato-N1,N2 (2), tetrazolato-N1,N2 (3), or tetrazolato-N2,N3 (4), were
      performed in cisplatin-sensitive and -resistant human non-small-cell lung cancer
      cell lines (PC-9 and PC-14). These complexes largely circumvented the cisplatin
      resistance in both cell lines, with resistance factors for 1-4 in the range of
      0.5-0.8 and 0.9-2.0 for PC-9 and PC-14 cells, respectively. Complex 4 exhibited
      approximately 10 times the cytotoxicity of 3. When 3 and 4 were reacted with 2
      molar equiv. of 9-ethylguanine (9EtG), they yielded an identical product, [{cis
      Pt(NH(3))(2)(9EtG-N7)}(2)(MU-tetrazolato-N1,N3)](3+), that had N1,N3 platinum
      coordination through a Pt(II) migration process on the tetrazolate ring. The
      second-order rate kinetics of these isomers were almost the same as each other
      and faster than those of 1 and 2. The cytotoxicity of azolato-bridged complexes,
      except for 3, increases as their kinetic rates in the 9EtG reaction increase.

PMID- 22473093
TI  - Neuroendocrine cancer: Combining two radiopeptide therapies improves survival.

PMID- 22473094
TI  - Kidney cancer: High-dose intermittent sunitinib therapy retains the crown.

PMID- 22473095
TI  - Diagnosis: Cancer diagnosis in UK primary care.

PMID- 22473096
TI  - Treatment selection in metastatic renal cell carcinoma: expert consensus.
AB  - In metastatic renal cell carcinoma (mRCC), many factors influence clinical
      decisions, including histology, tumour burden, prognostic factors, comorbidities,
      and the ability of the patient to tolerate treatment. Progression-free survival
      (PFS) durations reported from randomized trials of targeted therapies vary
      considerably, in part because of differences in patient characteristics. For
      first-line therapy, an estimate of PFS with sunitinib, bevacizumab plus
      interferon, or sorafenib in a 'general' population is 8-9 months, but each
      regimen is suitable for different patient categories. For example, sunitinib is
      suitable for all-prognosis groups, particularly younger, fitter patients;
      pazopanib for patients with a good or intermediate prognosis; bevacizumab plus
      interferon for good-prognosis patients or those with indolent disease; and
      sorafenib for patients at all prognostic risk levels, particularly the elderly
      and those with comorbidities. Sequential therapy with targeted agents provides
      significant benefit, and should be considered in all patients who can tolerate
      such treatment. Level 1 evidence supports sequential use of tyrosine kinase
      inhibitors, as well as these agents followed by everolimus. We consider how
      patient characteristics have influenced the results of studies of first-line
      therapy, and we provide expert opinion on the most appropriate treatment choices
      for particular patient groups receiving first-line and second-line therapy.

PMID- 22473097
TI  - The role of aspirin in cancer prevention.
AB  - Clinical guidelines for prophylactic aspirin use currently only consider the
      cardiovascular benefits of aspirin, weighed against the potential harm from
      aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce
      the risk of colorectal cancer and recurrence of adenomatous polyps, but in
      average-risk populations, these benefits alone do not outweigh harms from aspirin
      induced bleeding. Recently published secondary analyses of cardiovascular trials
      provide the first randomized evidence that daily aspirin use may also reduce the
      incidence of all cancers combined, even at low doses (75-100 mg daily). This
      Review considers the general mechanism of action that defines aspirin and other
      non-steroidal anti-inflammatory drugs (NSAIDs) as a class, the specific
      advantages of aspirin over other NSAIDs for prophylactic use, the current
      evidence concerning the main health outcomes affected by aspirin use, and the
      hypothesis that inhibition of platelet activation may mediate both the
      cardioprotective and cancer-preventive effects of low-dose aspirin. It also
      considers how even a 10% reduction in overall cancer incidence beginning during
      the first 10 years of treatment could tip the balance of benefits and risks
      favourably in average-risk populations.

PMID- 22473098
TI  - Breast cancer: Risk and mortality after oestrogen-alone therapy--is it safe?

PMID- 22473099
TI  - Genetics: Cells line up to be characterized.

PMID- 22473100
TI  - Haematological cancer: Turning the clock back on clonal evolution.

PMID- 22473101
TI  - Genetics: TKI resistance: finding the crack in the BIM.

PMID- 22473103
TI  - Gastrointestinal cancer: Should colonoscopy be a primary test in CRC screening?

PMID- 22473102
TI  - Treating ALK-positive lung cancer--early successes and future challenges.
AB  - Rearrangements of the anaplastic lymphoma kinase (ALK) gene occur infrequently in
      non-small-cell lung cancer (NSCLC), but provide an important paradigm for
      oncogene-directed therapy in this disease. Crizotinib, an orally bioavailable
      inhibitor of ALK, provides significant benefit for patients with ALK-positive
      (ALK+) NSCLC in association with characteristic, mostly mild, toxic effects, and
      this drug has been approved by the FDA for clinical use in this molecularly
      defined subgroup of lung cancer. Many new ALK inhibitors are being developed and
      understanding the challenges of determining and addressing the adverse effects
      that are likely to be ALK specific, while maximizing the time of benefit on
      targeted agents, and understanding the mechanisms that underlie drug resistance
      will be critical in the future for informing the optimal therapy of ALK+ NSCLC.

PMID- 22473104
TI  - Gastrointestinal cancer: The PROs and cons of liver resection in colorectal
      cancer.

PMID- 22473105
TI  - Molecular prescreening to select patient population in early clinical trials.
AB  - The efficacy of targeted therapies in patient populations selected for treatment
      on the basis of the molecular features of their tumours is shifting the current
      focus of treatment to biomarker-driven clinical trials. Phase I trials provide an
      arena for early hypothesis testing, examining not only safety and toxicity, but
      also target engagement, biologically effective dosages, and the appropriate
      patient population. In this Perspectives article, we describe this new trend in
      early drug development, establishing the different approaches for building a pre
      screening programme in an academic institution that is involved in early drug
      development. Our experience establishing the phase I programme at Vall d'Hebron
      serves as an example of how these approaches can be integrated in ongoing trials,
      and we believe these considerations will help others to implement similar
      programmes in their institutions.

PMID- 22473107
TI  - Transoral robotic surgery with laser for head and neck cancers: a feasibility
      study.
AB  - AIMS: To assess the feasibility of a flexible thulium laser coupled with a novel
      robotic introducer for head and neck cancers. METHODS: In a prospective
      nonrandomized clinical trial, 58 patients were evaluated. When indicated,
      transoral robotic surgery (TORS) with laser was performed using an Intuitive da
      Vinci S System with the Intuitive Surgical(r) Endo Wrist Introducer, 5Fr to hold
      and position thulium surgical laser fibers. RESULTS: Six patients underwent TORS
      with laser for early supraglottic and oropharyngeal squamous cell carcinomas. All
      approaches were successfully completed without the need for microscopic/open
      conversion or positive margins to the final pathological study. No intraoperative
      adverse events occurred and recovery was relatively quick, with no evidence of
      disease recurrence at the time of reporting, the short observation time
      notwithstanding. CONCLUSIONS: In our preliminary experience, TORS with laser
      showed feasible and promising results. Further studies are mandatory to
      demonstrate thulium laser benefits in surgical and oncological practice.

PMID- 22473109
TI  - Information, knowledge, and wisdom in public health surveillance.

PMID- 22473110
TI  - Using Medicaid claims to identify children with asthma.
AB  - OBJECTIVE: To assess the accuracy of using administrative data from state-managed
      programs to identify children with asthma in a statewide immunization information
      system. We wished to understand the degree to which alternative asthma case
      definitions applied to administrative data influence the accuracy of cases
      identified in an immunization information system. DESIGN & SETTING: Children aged
      2 to 18 years were sequentially classified into 3-case definition groups on the
      basis of Michigan Department of Community Health administrative data (2005-2006):
      (1) children with a Children's Special Health Care Services (CSHCS) Program
      qualifying diagnosis of asthma (CSHCS cases); (2) those having 1 or more asthma
      medication claims (Rx cases); or (3) those without asthma medications having 1 or
      more health services claim reporting an asthma diagnosis code (Dx cases).
      PARTICIPANTS: Children were randomly selected from each asthma case definition
      group; parents were invited to participate in a telephone interview to document
      physician diagnosis of asthma, symptoms, activity limitations, medications, and
      asthma health services use. MAIN OUTCOME MEASURES: The positive predictive value
      of parent report of a physician diagnosis of asthma; asthma severity, based on
      National Asthma Education and Prevention Program criteria. RESULTS: : Of 440
      completed interviews, 89% of parents confirmed the child's high-risk status,
      reporting physician diagnosis of asthma (83%), wheezy-cough (5%), or reactive
      airway disease (1%). The positive predictive value varied for CSHCS cases (100%),
      Rx cases (91%) and Dx cases (73%, P < .0001). Although reported asthma severity
      levels were similar among CSHCS and Rx cases (P = .9100), asthma severity was
      lower among Dx cases (P = .0218). CONCLUSIONS: Medicaid administrative data can
      be used to accurately identify children with asthma and represents a feasible
      approach for Medicaid programs and health plans to identify priority groups for
      targeted influenza vaccination reminders.

PMID- 22473111
TI  - Identifying children with chronic conditions for influenza vaccination using a
      statewide immunization registry:  initial experiences of primary care providers.
AB  - CONTEXT: Children with chronic medical conditions are at increased risk of
      complications from influenza, yet their vaccination rates are low. The Michigan
      Care Improvement Registry (MCIR), a statewide immunization registry, was expanded
      in 2006 to include an indicator, based on Medicaid administrative claims, that
      prompts providers to offer influenza vaccine to high-risk children (ie, those
      with chronic conditions). OBJECTIVE: To assess primary care providers'
      experiences with the MCIR high-risk indicator. DESIGN: A cross-sectional, self
      administered survey mailed in July 2009. SETTING: State of Michigan.
      PARTICIPANTS: A total of 300 family physicians and 300 pediatricians who served
      as primary care providers for children in Michigan's Medicaid program. MAIN
      OUTCOME MEASURES: Provider experiences with the high-risk indicator; suggestions
      for improvement. RESULTS: Response rate was 79%. Only 32% of pediatricians and
      17% of family physicians recalled seeing the high-risk indicator during the 2008
      2009 influenza season. Of those who saw the indicator, 48% rated it as "helpful"
      or "very helpful" in identifying which children should receive flu vaccine. To
      improve its usefulness, 77% of respondents wanted the indicator to reflect all
      children, rather than only those enrolled in Medicaid, and 71% wanted MCIR to
      generate a list of high-risk children in their practice. CONCLUSIONS: Three years
      after implementation, the registry-based high-risk indicator is not viewed by
      most providers. Half of those who saw the indicator found it helpful, and most
      respondents endorsed enhancements to broaden its scope. Future work should
      explore whether enhanced capabilities help to facilitate identification of
      priority cases by providers.

PMID- 22473112
TI  - Comparison of electronic laboratory reports, administrative claims, and
      electronic health record data for acute viral hepatitis surveillance.
AB  - CONTEXT: Public health surveillance systems for acute hepatitis are limited:
      clinician reporting is insensitive and electronic laboratory reporting is
      nonspecific. Insurance claims and electronic health records are potential
      alternative sources. OBJECTIVE: To compare the utility of laboratory data,
      diagnosis codes, and electronic health record combination data (current and prior
      viral hepatitis studies, liver function tests, and diagnosis codes) for acute
      hepatitis A and B surveillance. DESIGN: Retrospective chart review. SETTING:
      Massachusetts ambulatory practice serving 350 000 patients per year.
      PARTICIPANTS: All patients seen between 1990 and 2008. MAIN OUTCOME MEASURES:
      Sensitivity and positive predictive value of immunoglobulin M (IgM),
      International Classification of Disease-Ninth Revision (ICD-9) diagnosis codes,
      and combination electronic health record data for acute hepatitis A and B.
      RESULTS: During the study period, there were 111 patients with positive hepatitis
      A IgMs, 154 with acute hepatitis A ICD-9 codes, and 77 with positive IgM and
      elevated liver function tests. On review, 79 cases were confirmed. Sensitivity
      and positive predictive value were 100% and 71% (95% confidence interval, 62%
      79%) for IgM, 94% (92%-100%) and 48% (40%-56%) for ICD-9 codes and 97% (92%-100%)
      and 100% (96%-100%) for combination electronic health record data. There were 14
      patients with positive hepatitis B core IgMs, 2564 with acute hepatitis B ICD-9
      codes, and 125 with suggestive combinations of electronic health record data.
      Acute hepatitis B was confirmed in 122 patients. Sensitivity and positive
      predictive value were 9.4% (5.2%-16%) and 86% (60%-98%) for hepatitis B core IgM,
      73% (65%-80%) and 3.6% (2.9%-4.4%) for ICD-9 codes, and 96% (91%-99%) and 98%
      (94%-99%) for electronic health record data. CONCLUSIONS: Laboratory surveillance
      using IgM tests overestimates the burden of acute hepatitis A and underestimates
      the burden of acute hepatitis B. Claims data are subject to many false positives.
      Electronic health record data are both sensitive and predictive. Electronic
      health record-based surveillance systems merit development.

PMID- 22473113
TI  - The utilization rate of the regional health information exchange: how it impacts
      on health care delivery outcomes.
AB  - Interest in improving quality and effectiveness is the primary driver for health
      information exchange efforts across a health care system to improve the provision
      of public health care services. OBJECTIVE: The aim here was to describe and
      identify the impact of a regional health information exchange (HIE) using
      quantitative statistics for 2004-2008 in one hospital district in Finland.
      DESIGN: We conducted a comparative, longitudinal 5-year follow-up study to
      evaluate the utilization rates of HIE, and the impact on health care delivery
      outcomes. The selected outcomes were total laboratory tests, radiology
      examinations, appointments, emergency visits, and referrals. RESULTS: The HIE
      utilization rates increased annually in all 10 federations of municipalities, and
      the viewing of reference information increased steadily in each professional
      group over the 5-year study period. In these federations, a significant
      connection was found to the number of laboratory tests and radiology
      examinations, with a statistically significant increase in the number of viewed
      references and use of HIE. The higher the numbers of emergency visits and
      appointments, the higher the numbers of emergency referrals to specialized care,
      viewed references, and HIE usage among the groups of different health care
      professionals. CONCLUSIONS: There is increasing interest in HIE usage through
      regional health information system among health professionals to improve health
      care delivery regionally and bring information on the patient directly to care
      delivery. It will be important to study which changes in working methods in the
      service system are explained by RHIS. Also, the experiences of the change that
      has taken place should be studied among the different stakeholders,
      administrative representatives, and patients.

PMID- 22473114
TI  - Impact of integrating public health clinical decision support alerts into
      electronic health records on testing for gastrointestinal illness.
AB  - Laboratory testing by clinicians is essential to outbreak investigations.
      Electronic health records may increase testing through clinical decision support
      that alerts providers about existing outbreaks and facilitates laboratory
      ordering. The impact on laboratory testing was evaluated for foodborne disease
      outbreaks between 2006 and 2009. After controlling for standard public health
      messaging and season, decision support resulted in a significant increase in
      laboratory testing and may be useful in enhancing public health messaging and
      provider action.

PMID- 22473115
TI  - Access to scientific information:  from counting to accountability.

PMID- 22473116
TI  - Preparedness for pandemics: does variation among states affect the nation as a
      whole?
AB  - OBJECTIVE: Since states' public health systems differ as to pandemic
      preparedness, this study explored whether such heterogeneity among states could
      affect the nation's overall influenza rate. DESIGN: The Centers for Disease
      Control and Prevention produced a uniform set of scores on a 100-point scale from
      its 2008 national evaluation of state preparedness to distribute materiel from
      the Strategic National Stockpile (SNS). This study used these SNS scores to
      represent each state's relative preparedness to distribute influenza vaccine in a
      timely manner and assumed that "optimal" vaccine distribution would reach at
      least 35% of the state's population within 4 weeks. The scores were used to
      determine the timing of vaccine distribution for each state: each 10-point
      decrement of score below 90 added an additional delay increment to the
      distribution time. SETTING AND PARTICIPANTS: A large-scale agent-based
      computational model simulated an influenza pandemic in the US population. In this
      synthetic population each individual or agent had an assigned household, age,
      workplace or school destination, daily commute, and domestic intercity air travel
      patterns. MAIN OUTCOME MEASURES: Simulations compared influenza case rates both
      nationally and at the state level under 3 scenarios: no vaccine distribution
      (baseline), optimal vaccine distribution in all states, and vaccine distribution
      time modified according to state-specific SNS score. RESULTS: Between optimal and
      SNS-modified scenarios, attack rates rose not only in low-scoring states but also
      in high-scoring states, demonstrating an interstate spread of infections.
      Influenza rates were sensitive to variation of the SNS-modified scenario (delay
      increments of 1 day versus 5 days), but the interstate effect remained.
      CONCLUSIONS: The effectiveness of a response activity such as vaccine
      distribution could benefit from national standards and preparedness funding
      allocated in part to minimize interstate disparities.

PMID- 22473117
TI  - Do people become better prepared in the aftermath of a natural disaster? The
      hurricane Ike experience in Houston, Texas.
AB  - OBJECTIVE: Despite large-scale efforts and expensive public education campaigns
      mounted by the government at all levels in the past decade, the improvements in
      disaster preparedness among the US Gulf Coast residents have been ineffectual at
      best. Some factors that contribute to better preparedness are past experience,
      awareness of what to do in a disaster scenario and availability, and access to
      informational and supportive resources. We examine whether an experience of a
      natural disaster brings about changes in preparedness and access to resources.
      DESIGN: Our study is based on data from 2 cross-sectional random-digit-dialing
      surveys in 2008 (pre-Ike) and 2009 (post-Ike) with sample sizes of 1001 and 1009,
      respectively. PARTICIPANTS: Adults living in one of the 85 zip codes in Houston,
      Texas. MAIN OUTCOME MEASURE: Self-reported preparedness, evacuation plan,
      available resources (informational, financial and emotional). RESULTS: We found
      no significant changes in preparedness or evacuation plans in residents of
      Houston prior to and a year after Hurricane Ike. Hispanics and other minority
      groups reported a significant increase in access to information and all residents
      reported an increase in perception of availability of financial support, if
      needed. Perceived availability of tangible (financial) support has been linked to
      positive physical and mental health effects and can contribute to resiliency and
      quicker recovery. The unchanged preparedness levels could be attributed to
      ceiling effects, that is, the already high levels of preparedness reported by
      Houston residents. Greater access to information reported by Hispanics and other
      minorities is encouraging and indicative of success in reaching out. CONCLUSIONS:
      Our results also indicate a greater need for appropriate targeted strategies to
      reach out to African Americans in Houston since this group reported poorer access
      to information. This has implications for planning and preparedness officials and
      the communication strategies used to reach the community.

PMID- 22473118
TI  - A taxonomy of state public health preparedness units:  an empirical examination
      of organizational structure.
AB  - OBJECTIVE: State public health preparedness units (SPHPUs) were developed in
      response to federal funding to improve response to disasters: a responsibility
      that had not traditionally been within the purview of public health. The SPHPUs
      were created within the existing public health organizational structure, and
      their placement may have implications for how the unit functions, how
      communication takes place, and ultimately how well the key responsibilities are
      performed. This study empirically identifies a taxonomy of similarly structured
      SPHPUs and examines whether this structure is associated with state geographic,
      demographic, and threat-vulnerability characteristics. DESIGN: Data representing
      each SPHPU were extracted from publically available sources, including
      organizational charts and emergency preparedness plans for 2009. A cross
      sectional segmentation analysis was conducted of variables representing
      structural attributes. SETTING AND PARTICIPANTS: Fifty state public health
      departments. MAIN OUTCOME MEASURES: Variables representing "span of control" and
      "hierarchal levels" were extracted from organizational charts. Structural
      "complexity" and "centralization" were extracted from state emergency
      preparedness documents and other secondary sources. RESULTS: On average, 6.6
      people report to the same manager as the SPHPU director; 2.1 levels separate the
      SPHPU director from the state health officer; and a mean of 13.5 agencies
      collaborate with SPHPU during a disaster. Despite considerable variability in how
      SPHPUs had been structured, results of the cluster and principal component
      analysis identified 7 similarly structured groups. Neither the taxonomic groups
      nor the individual variables representing structure were found to be associated
      with state characteristics, including threat vulnerabilities. CONCLUSIONS: Our
      finding supports the hypothesis that SPHPUs are seemingly inadvertently (eg, not
      strategically) organized. This taxonomy provides the basis for which future
      research can examine how SPHPU structure relates to performance measures and
      preparedness strategies.

PMID- 22473119
TI  - Comparison of methods for estimating the cost of human immunodeficiency virus
      testing interventions.
AB  - CONTEXT: The Centers for Disease Control and Prevention (CDC), Division of
      HIV/AIDS Prevention, spends approximately 50% of its $325 million annual human
      immunodeficiency virus (HIV) prevention funds for HIV-testing services. An
      accurate estimate of the costs of HIV testing in various settings is essential
      for efficient allocation of HIV prevention resources. OBJECTIVES: To assess the
      costs of HIV-testing interventions using different costing methods. DESIGN,
      SETTINGS, AND PARTICIPANTS: We used the microcosting-direct measurement method to
      assess the costs of HIV-testing interventions in nonclinical settings, and we
      compared these results with those from 3 other costing methods: microcosting
      staff allocation, where the labor cost was derived from the proportion of each
      staff person's time allocated to HIV testing interventions; gross costing, where
      the New York State Medicaid payment for HIV testing was used to estimate program
      costs, and program budget, where the program cost was assumed to be the total
      funding provided by Centers for Disease Control and Prevention. MAIN OUTCOME
      MEASURES: Total program cost, cost per person tested, and cost per person
      notified of new HIV diagnosis. RESULTS: The median costs per person notified of a
      new HIV diagnosis were $12 475, $15 018, $2697, and $20 144 based on microcosting
      direct measurement, microcosting-staff allocation, gross costing, and program
      budget methods, respectively. Compared with the microcosting-direct measurement
      method, the cost was 78% lower with gross costing, and 20% and 61% higher using
      the microcosting-staff allocation and program budget methods, respectively.
      CONCLUSIONS: Our analysis showed that HIV-testing program cost estimates vary
      widely by costing methods. However, the choice of a particular costing method may
      depend on the research question being addressed. Although program budget and
      gross-costing methods may be attractive because of their simplicity, only the
      microcosting-direct measurement method can identify important determinants of the
      program costs and provide guidance to improve efficiency.

PMID- 22473120
TI  - Variations in positive predictive values for rapid influenza tests for 2009
      pandemic influenza a (pH1N1)--Arizona, April-October 2009.
AB  - CONTEXT: Rapid influenza diagnostic tests (RIDTs) are used for influenza
      screening, clinical decision making, and influenza surveillance. In August 2009,
      a hospital reported increased false-positive RIDT results to the Arizona
      Department of Health Services. Because of reported RIDT low sensitivities (40%
      62%) for 2009 pandemic influenza A (pH1N1), the hospital's report raised further
      concerns about the specificity and clinical utility of RIDTs. OBJECTIVE: To
      determine the positive predictive value (PPV) of RIDTs compared with real-time
      reverse transcription-polymerase chain reaction assay (rRT-PCR) using Centers for
      Disease Control and Prevention (CDC) protocols and primers as a standard. DESIGN:
      A standardized survey collected information including RIDT brand/lot number,
      training of personnel performing test, type of laboratory, swab and specimen
      type, time from collection to testing, sample storage, and viral transport
      medium. SETTING: Arizona. PARTICIPANTS: Seven Arizona laboratories submitted
      positive RIDT clinical samples to Arizona State Public Health Laboratory (ASPHL)
      for confirmatory rRT-PCR testing. MAIN OUTCOME MEASURE: The PPV was calculated on
      the basis of rRT-PCR-positive results for April through October. RESULTS: Results
      from 600 specimens using 1 of 4 RIDTs were available. Median pH1N1 PPV was 80%
      (range: 62%-91%) when calculated by RIDT brand. A significant difference in PPV
      was identified between the 2 largest facilities, which used the same RIDT brand,
      BinaxNOW Influenza A&B, (Laboratories A, 33% and B, 92%, [P < .01]). The
      facilities reported similar testing practices except lot numbers used and timing
      of testing. Laboratory A used lot 003684 and performed testing within 1 hour of
      collection; Laboratory B used multiple lots, excluding lot 003684, and performed
      testing within 24 hours. Laboratory A switched RIDT brands and noted a
      significant PPV increase from 33% to 91% (P < .01). CONCLUSIONS: Wide PPV
      variability combined with documented low sensitivity among RIDTs for pH1N1
      diagnosis increases concerns about their specificity and clinical and
      epidemiologic utility for influenza.

PMID- 22473121
TI  - Residential carbon monoxide alarm prevalence and ordinance awareness.
AB  - OBJECTIVE: Unintentional carbon monoxide (CO) poisoning is a leading cause of
      poisoning in the United States. Most poisoning cases occur in residential
      settings and a working CO alarm may prevent many of these events. The use of a CO
      alarm is mandated in many parts of the country; however, little is known about
      the compliance and adoption of such ordinances at the population level. This
      study determined the prevalence of residential CO alarm and awareness of a 2001
      CO alarm ordinance in Mecklenburg County, North Carolina in 2009. METHODS: A
      random sample of households stratified by housing type (eg, single-family homes,
      multifamily homes) was included in a cross-sectional survey conducted. One adult
      respondent from each household was administered a questionnaire that included
      information on sociodemographic and household characteristics, presence of a CO
      alarm, and CO alarm ordinance awareness. Data were analyzed using multivariate
      stratified conditional logistic regression. RESULTS: Among 214 participating
      households (response rate, 23.4%), 145 (67.8%) reported having a working CO alarm
      and 79 (36.9%) of the respondents were aware of the CO alarm ordinance.
      Respondents who were aware of the ordinance had 9 times higher odds (95%
      confidence interval, 3.3-25.9) of having a CO alarm than those who were unaware.
      Also, households with an attached garage had more than 2 times higher odds (95%
      confidence interval, 1.0-6.2) of having a CO alarm than those without an attached
      garage. Awareness of the CO alarm ordinance was not associated with any
      sociodemographic (eg, age, sex, race, education, income) or household (eg, home
      ownership, home construction year) characteristics. CONCLUSIONS: Carbon monoxide
      alarm prevalence in Mecklenburg County households was higher than the national
      average and was associated with CO alarm ordinance awareness. Public health
      efforts might benefit from regulations aimed at population-level adoption of
      preventive health behaviors.

PMID- 22473122
TI  - Partnering for health: collaborative leadership between a community health center
      and the YWCA central Massachusetts.
AB  - BACKGROUND: A collaborative partnership among community-based organizations
      (CBOs)-a community-health center, a YWCA, and 2 academic health centers-developed
      and implemented open access to physical activity for health center patients.
      OBJECTIVE: To describe partnership approach taken by 2 CBOs; determine staffs'
      views of this unique partnership, highlight aspects of the partnership that
      contributed to its success, identify challenges and mechanisms for overcoming
      them, and note lessons learned. Assess health center patients' use of YWCA
      facility. METHODS: Usage data were obtained from YWCA records. Staff were
      interviewed using primarily open-ended questions. Inductive approach was used to
      analyze qualitative data. RESULTS: The approach to partnership was largely
      organic, without formal working documents; nevertheless, the partnership
      reflected the organizations' missions. Over 4 years, 1134 health center patients
      made more than 23 000 visits to the YWCA. Responses of health center staff and
      provider interviewees about partnership processes sorted into the following
      categories: partnership description and results, partnership benefits,
      challenges, lessons learned, and advice to other CBOs. YWCA staff interviewee
      responses reflected the categories: staffing, clientele, and public face.
      Comments also included challenges, lessons learned, and advice to other YWCAs.
      CONCLUSIONS: This partnership achieved notable successes largely because (a) it
      formed to serve a specific purpose that met both agencies' goals, (b) leaders
      made sustained commitments, and (c) it managed conflict. The partnership has
      taken on new projects over time; new ideas for improving access and service to
      underserved patients continue to emerge. Interorganizational trust and allegiance
      have been key to addressing challenges; nevertheless, the organic nature of the
      partnership's origins and the challenges of success have meant that the
      partnership has restructured its agreement and, to avoid being overwhelmed,
      limited new patient use.

PMID- 22473123
TI  - Aligning health informatics across the public health enterprise.

PMID- 22473124
TI  - Partners in program planning for adolescent health:  a unique approach to
      multidisciplinary collaboration.

PMID- 22473126
TI  - State requirements for rabies-related animal control.
AB  - OBJECTIVE: Rabies postexposure prophylaxis is an important secondary prevention
      step but is unnecessary if the exposing animal is not rabid. Effective rabies
      related animal control (RRAC) requirements enforced by animal control officers
      (ACO) are an alternative step to reduce the number of rabies exposures and
      postexposure prophylaxes. The purpose of this study was to describe the
      variability of requirements for RRAC by statutes and regulations across the
      United States. METHODS: Current state laws and regulations pertaining to rabies
      and animal control were reviewed and assessed for 3 primary RRAC activities
      related to obtaining animals that have potentially exposed humans to rabies, that
      have been potentially exposed to rabies, or that show signs of rabies. Animal
      control infrastructure was assessed on the basis of the requirement for, and
      authority granted to, ACOs for conducting these RRAC activities. State Public
      Health Veterinarians, State Veterinarians with the Departments of Agriculture,
      and/or State Epidemiologists were contacted for verification and assistance with
      interpretation of laws and regulations. RESULTS: Twenty-three states and the
      District of Columbia authorize specific actions related to all 3 RRAC activities.
      Twenty-four states have laws and regulations that do not clearly address at least
      1 of the RRAC activities or limit the authority to domestic animals. Three states
      have laws or regulations that address RRAC nonspecifically or leave the
      requirements to localities. Eleven states mandate the placement of ACOs with
      authority over domestic and wild animals, 7 states require ACOs for control of
      domestic animals only, and 32 states and the District of Columbia have no
      statewide requirements for ACOs. DISCUSSION: Only 9 states have legal
      requirements for ACOs with authority over wild and domestic animals and RRAC that
      addresses all 3 primary RRAC activities. Consequently, RRAC requirements may
      represent an incompletely tapped rabies prevention mechanism.

PMID- 22473125
TI  - Public health nursing job descriptions:  are they aligned with professional
      standards?
AB  - OBJECTIVES: The American Nurses' Association (ANA) 2007 Public Health Nursing:
      Scope and Standards of Practice along with the Quad Council's PHN competencies
      frame the practice of public health nurses (PHNs). The preface for ANA's PHN
      Scope and Standards encourages using the standards as the basis of PHN job
      descriptions. This study sought to assess the extent to which PHN job
      descriptions are aligned with the ANA's PHN Scope and Standards and the Quad
      Council competencies. DESIGN: We obtained PHN job descriptions from 3 local
      health departments in Illinois and 3 in Washington. Statements from the job
      descriptions were content analyzed, categorizing statements into the 16 ANA PHN
      Scope and Standards and using Quad Council competencies as additional definitions
      of each category. To code all job statements related to PHN practice, 2
      categories were added which were MPH competencies from the Associations of
      Schools of Public Health. Interrater reliability was established. RESULTS: All 18
      PHN job descriptions had statements related to Standard 5 Implementation,
      followed by 94% of the job descriptions having statements related to assessment,
      planning, coordination of services, health education/health promotion, and
      collaboration. The least frequently (22%) included standard was outcome
      identification. CONCLUSIONS: Attention to human resource management is necessary
      to align job descriptions with current professional scope and standards for basic
      and advanced PHN practice. The lack of statements regarding Outcome
      Identification has serious implications for PHN involvement in quality
      improvement and health planning.

PMID- 22473127
TI  - A fresh look at spay/neuter legislation:  the journey to a middle ground.
AB  - A hybrid body of regulations is recommended containing both mandatory spay/neuter
      and low-cost spay/neuter provisions that will reduce accidental litters, impulse
      buying, and other irresponsible pet practices. The majority of pet owners are
      well-meaning but often lack the financial, intellectual, or other resources to
      properly control the breeding behaviors of their animals. Full compliance with
      spay/neuter regulations is the most desirable solution to the pet overpopulation
      problem. A comprehensive rule structure will facilitate spaying and neutering in
      some circumstances and require it on others.

PMID- 22473128
TI  - Lessons learned from the 2007 to 2009 Haemophilus influenzae type B vaccine
      shortage: implications for future vaccine shortages and public health
      preparedness.
AB  - OBJECTIVE: To understand immunization programs' experience managing the 2007 to
      2009 Haemophilus influenzae type B (Hib) vaccine shortage and identify ways in
      which the US immunization system can be improved to assist in responses to future
      shortages of routine vaccines and large-scale public health emergencies. METHODS:
      An Internet-based survey was conducted from July 2009 to October 2009 among the
      64 city, state, and territorial immunization program managers (IPMs). RESULTS:
      Fifty-eight percent (37 of the 64) of IPMs responded. Forty percent of responding
      IPMs indicated not having enough Hib vaccine within their Vaccines for Children
      program to fulfill the temporary 3-dose recommendation issued in December 2007 in
      response to the Hib vaccine shortage. While 73% of IPMs indicated success in
      monitoring provider inventory and 68% indicated success in monitoring doses
      administered during the shortage, fewer than half indicated success in monitoring
      providers' compliance with shortage-specific recommendations regarding Hib
      vaccine. Forty-six percent of IPMs used their immunization information system
      (IIS) to monitor provider compliance with recommendations regarding Hib vaccine
      use, and of these, nearly 60% reported success in monitoring provider compliance
      with recommendations compared with 35% of IPMs who did not use their IIS in this
      way. Forty-two percent of IPMs felt that the Centers for Disease Control and
      Prevention (CDC) was successful in determining stockpiled vaccine allocations to
      their program, and 56% felt that the CDC was successful in communicating its
      rationale for their immunization program's Hib allocation during the shortage.
      CONCLUSIONS: Experiences from the 2007 to 2009 Hib vaccine shortage offer
      insights on how the US immunization system and system-wide response to vaccine
      shortages can be improved. Results from this survey suggest that improving
      vaccine transfer between jurisdictions and using IIS to track provider compliance
      with shortage recommendations are 2 ways that can help the US immunization system
      respond to future vaccine shortages and large-scale public health emergencies
      like influenza pandemics.

PMID- 22473129
TI  - P2X7 receptor-mediated calcium dynamics in HEK293 cells: experimental
      characterization and modelling approach.
AB  - The P2X7 receptor (P2X7R) induces ionotropic Ca2+ signalling in different cell
      types. It plays an important role in the immune response and in the nervous
      system. Here, the mechanisms underlying intracellular Ca2+ variations evoked by
      3'-O-(4-benzoyl)benzoyl-ATP (BzATP), a potent agonist of the P2X7R, in
      transfected HEK293 cells, are investigated both experimentally and theoretically.
      We propose a minimal model of P2X7R that is capable of reproducing, qualitatively
      and quantitatively, the experimental data. This approach was also adopted for the
      P2X7R variant, which lacks the entire C-terminus tail (trP2X7R). Then we
      introduce a biophysical model describing the Ca2+ dynamics in HEK293. Our model
      gives an account of the ionotropic Ca2+ influx evoked by BzATP on the basis of
      the kinetics model of P2X7R. To explain the complex Ca2+ responses evoked by
      BzATP, the model predicted that an impairment in Ca2+ extrusion flux through the
      plasma membrane is a key factor for Ca2+ homeostasis in HEK293 cells.

PMID- 22473130
TI  - Integration of FDG-PET/CT into external beam radiation therapy planning:
      technical aspects and recommendations on methodological approaches.
AB  - This work addresses the clinical adoption of FDG-PET/CT for image-guided
      radiation therapy planning (RTP). As such, important technical and methodological
      aspects of PET/CT-based RTP are reviewed and practical recommendations are given
      for routine patient management and clinical studies. First, recent developments
      in PET/CT hardware that are relevant to RTP are reviewed in the context of
      quality control and system calibration procedures that are mandatory for a
      reproducible adoption of PET/CT in RTP. Second, recommendations are provided on
      image acquisition and reconstruction to support the standardization of imaging
      protocols. A major prerequisite for routine RTP is a complete and secure data
      transfer to the actual planning system. Third, state-of-the-art tools for image
      fusion and co-registration are discussed briefly in the context of PET/CT imaging
      pre- and post-RTP. This includes a brief review of state-of-the-art image
      contouring algorithms relevant to PET/CT-guided RTP. Finally, practical aspects
      of clinical workflow and patient management, such as patient setup and
      requirements for staff training are emphasized. PET/CT-guided RTP mandates
      attention to logistical aspects, patient set-up and acquisition parameters as
      well as an in-depth appreciation of quality control and protocol standardization.
      CONCLUSION: Upon fulfilling the requirements to perform PET/CT for RTP, a new
      dimension of molecular imaging can be added to traditional morphological imaging.
      As a consequence, PET/CT imaging will support improved RTP and better patient
      care. This document serves as a guidance on practical and clinically validated
      instructions that are deemed useful to the staff involved in PET/CT-guided RTP.

PMID- 22473131
TI  - Effects of cinacalcet in renal transplant patients with hyperparathyroidism.
AB  - BACKGROUND: Cinacalcet decreases serum parathyroid hormone (PTH) and calcium
      concentrations in kidney transplant recipients with autonomous
      hyperparathyroidism. Long-term treatment with cinacalcet may increase urinary
      calcium excretion and the risk of renal calcium deposits and may alter renal
      graft function. METHODS: We studied 71 renal recipients with hypercalcemic
      hyperparathyroidism. Of these patients, 34 received cinacalcet between month 3
      and month 12 after renal transplantation. We compared phosphate calcium balance,
      measured glomerular filtration rate (GFR) and renal biopsies in cinacalcet
      treated and non-cinacalcet-treated patients. Measurements were performed before
      initiating cinacalcet treatment (month 3) and at month 12. RESULTS: Patients
      treated with cinacalcet had more severe hyperparathyroidism. Serum PTH
      concentration decreased in both groups between months 3 and 12, but the decrease
      was much more important in cinacalcet-treated patients. Urinary calcium excretion
      significantly increased under cinacalcet treatment and was more than twice as
      high at month 12 as in patients who did not receive cinacalcet treatment.
      However, the hypercalciuria was not associated with an increase in calcium
      deposits on renal biopsies or an alteration of measured GFR. CONCLUSIONS: Despite
      sustained and marked hypercalciuria induced by cinacalcet treatment, cinacalcet
      does not have adverse effects on GFR or on renal graft calcium deposits in the
      first year following renal transplantation.

PMID- 22473134
TI  - Aggregation-dependent photovoltaic properties of squaraine/PC61BM bulk
      heterojunctions.
AB  - In this study, we investigated bulk-heterojunction solar cells composed of
      PC(61)BM and squaraine dyes with different donor subunits. Both, H- and J
      aggregates, have been observed for the squaraine dyes in the mixture, even for
      the same dye depending on the annealing conditions of the blends. Supramolecular
      organization of the squaraine dyes noticeably affects solar cell performance. The
      J-aggregate exhibits a red-shift of the absorption maximum that results in a
      significant increase in the short-circuit current and decrease in the open
      circuit voltage compared to the as-cast device. The H-aggregate shows a blue
      shift in the absorption maximum and concomitantly only a moderate increase in the
      short-circuit current as well as an increase in the open-circuit voltage. The
      course of domain growth during annealing was monitored by local photocurrent
      mapping.

PMID- 22473132
TI  - Breaking the HAC Barrier: histone H3K9 acetyl/methyl balance regulates CENP-A
      assembly.
AB  - The kinetochore is responsible for accurate chromosome segregation. However, the
      mechanism by which kinetochores assemble and are maintained remains unclear. Here
      we report that de novo CENP-A assembly and kinetochore formation on human
      centromeric alphoid DNA arrays is regulated by a histone H3K9 acetyl/methyl
      balance. Tethering of histone acetyltransferases (HATs) to alphoid DNA arrays
      breaks a cell type-specific barrier for de novo stable CENP-A assembly and
      induces assembly of other kinetochore proteins at the ectopic alphoid site.
      Similar results are obtained following tethering of CENP-A deposition factors
      hMis18alpha or HJURP. HAT tethering bypasses the need for hMis18alpha, but HJURP
      is still required for de novo kinetochore assembly. In contrast, H3K9 methylation
      following tethering of H3K9 tri-methylase (Suv39h1) to the array prevents de novo
      CENP-A assembly and kinetochore formation. CENP-A arrays assembled de novo by
      this mechanism can form human artificial chromosomes (HACs) that are propagated
      indefinitely in human cells.

PMID- 22473133
TI  - Simultaneous determination of a novel diphenylpiperazine calcium channel blocker
      and its four metabolites in rat liver microsomes by liquid chromatography tandem
      mass spectrometry.
AB  - Dipfluzine hydrochloride (Dip), a novel diphenylpiperazine calcium channel
      blocker, has revealed the characteristics of a promising candidate for the
      treatment of cerebral vascular diseases in preclinical studies. Our research
      identified and quantified Dip and its 4 metabolites (M1, M2, M4 and M5) in rat
      liver microsomes by liquid chromatography tandem mass spectrometry. The results
      showed that Dip was firstly metabolized to M1 and M5 by 1- and 4-dealkylation
      from a piperazine nitrogen, and then the latter was subsequently metabolized to
      M2 and M4. The concentrations of Dip, M1, M2 and M5 were 557.3 +/- 26.3, 854.3 +/
      46.0, 2796.7+/- 126.9, 2473.3 +/- 82.6 and 4.0 +/- 0.4, 2.4 +/- 0.1, 318.2 +/-
      8.7 and 27.4 +/- 1.5 ng/ml in male and female rats, respectively. M4 (404.2 +/-
      22.2 ng/ml) was detected only in males not in females, suggesting that there is
      gender difference in the metabolism of Dip.

PMID- 22473135
TI  - Clinical review of pediatric epilepsy.
AB  - Seizure disorders are very common and represent the most common cause of
      referrals to pediatric neurology. Epilepsy, defined as recurrent unprovoked
      seizures, is also common with a frequency of 4-8 cases per 1000 children. In
      Saudi Arabia, inherited neurological disorders, including epilepsy and genetic
      epilepsy syndromes, are more common because of the high rate of consanguinity.
      This article attempts to provide an updated overview of pediatric epilepsy and
      review the most recent diagnostic and therapeutic guidelines. Seizures in
      children have wide variations in clinical expression with age specific
      presentation. Although epilepsy is a clinical diagnosis, EEG often provides
      supportive evidence and helps in seizure classification. Epilepsy syndromes are
      more common in younger children, and their proper diagnosis provides valuable
      genetic, therapeutic, and prognostic information. Magnetic resonance imaging is
      superior in identifying congenital or developmental abnormalities and should be
      performed in preference to CT. Monotherapy is the best management approach for
      better compliance and to prevent interactions or side effects. To conclude,
      epilepsy remains a clinical diagnosis and therefore, careful and detailed history
      remains the cornerstone of an accurate clinical diagnosis.

PMID- 22473136
TI  - Autoimmune connection of autism in Central Saudi Arabia.
AB  - OBJECTIVE: Autism is a neurodevelopmental disorder with unknown etiology. The
      etiology of autism is complex, and the underlying pathologic mechanisms are
      unknown. This study tests the autoimmune mechanisms in the pathogenesis for
      autism in autistic children in the Riyadh area. METHODS: The study took place in
      the Riyadh area of the Kingdom of Saudi Arabia between September 2003 and April
      2004. Sixty-five autistic children, with a confirmed diagnosis according to E-2
      diagnostic criteria for autistic spectrum disorders, participated in the study.
      Serological examination of antibodies to measles, mumps, rubella (MMR), and
      myelin basic protein (MBP) was carried out in autistic and control children.
      RESULTS: The level of MBP antibodies was significantly higher in autistic
      children as compared to controls (p<0.01). Furthermore, the level of antibodies
      to measles but not mumps or rubella was significantly higher in autistics
      compared to the control group (p<0.05). Moreover, 82% of autistic sera positive
      for measles IgG was also positive for MBP. CONCLUSION: The current study supports
      the hypothesis that autoimmunity plays a role in the pathogenesis of autism.
      However, results from the current study are not enough to support that
      immunization by MMR is playing a role in the autoimmune process in autistism.

PMID- 22473137
TI  - Skin findings related to chronic usage of anti-epileptic drugs.
AB  - OBJECTIVE: Chronic type skin reactions are defined as unwanted effects of drugs. 
      As there are more benign conditions, skin findings related to chronic usage of
      anti-epileptic drugs (AEDs) have not been studied previously. In this study, we 
      investigate the skin findings associated with the chronic usage of AEDs. METHODS:
      The study was conducted in the Post, Telephone and Telegraph Training and
      Research Hospital between May 2002 and January 2003 during a 6-month work period.
      Skin lesions were first assessed individually, and then their correlations with
      AEDs were examined. Skin findings were then divided into skin disease groups to
      evaluate statistical significance. The prevalence of skin findings occurring in
      62 epileptics was compared with that of an age-matched group of 33 non
      epileptics. RESULTS: The rate of skin findings defined in the workgroup was
      85.5%, while it was 84.8% in the control group. The most common skin findings
      were acneiform eruptions for both groups. There were no significant differences
      between the work and study group for skin findings (p>0.05). Alopecia was the
      only skin condition related to AED usage and it was seen in 4 patients (6.5%)
      using valproate (p<0.05). None of the 11 patients with infectious skin findings
      were using valproate, and that was the only significant relationship between
      antiepileptic drugs and skin diseases (p=0.015). CONCLUSION: The inflammatory
      skin diseases were the most commonly seen problem in both patients and controls.
      The alopecia ratio with valproate usage in our patient group was similar to
      literature reports.

PMID- 22473138
TI  - Impressions and experience of non-neurologists in neurology.
AB  - OBJECTIVE: Neurological disorders are common in Saudi Arabia and the demand for
      trained neurologists is strong. We aimed to study the impressions and experiences
      of general physicians in the neurology field and examine their referral
      practices. METHODS: We included attendees of the 'neurology for non-neurologists'
      symposium, which took place from 14-15 October 2004 at King Faisal Specialist
      Hospital and Research Center in Jeddah, Kingdom of Saudi Arabia. We designed a
      structured 24-item questionnaire to examine their demographics, training,
      practice, and referral patterns. RESULTS: One hundred and eight participants
      registered for the symposium, with 69 (64%) questionnaires returned. Attendee's
      ages were 23-60 years (mean 35), with 53% being males. There were 46% consultants
      and specialists, 33.5% trainees, 14.5% students, and 6% other health
      professionals. Most physicians (62%) practiced in the field of general practice
      or internal medicine and 62% received a structured neurology rotation during
      training. Patients with neurological complaints constituted 29.5% of those seen
      in their practice, and they referred 33.3% to neurology. Only 13.5% and 15.5%
      were highly confident in diagnosing and treating these patients. Those who
      reported seeing many patients with neurological complaints (4 on the Likert
      scale) were 18.8 times more likely to feel highly confident in their diagnoses
      (95% confidence interval [CI]: 3-195, p=0.0002) and 23 times more likely to feel
      highly confident in their management (95% CI: 3.6-236, p=0.0005). Many physicians
      (20.5%) had no direct access to a neurologist for referrals. CONCLUSION: Many
      general physicians were not highly confident in diagnosing and treating neurology
      patients. Given the limited number of neurologists, we recommend appropriate
      neurological training of generalists.

PMID- 22473139
TI  - The efficacy of Schroth's 3-dimensional exercise therapy in the treatment of
      adolescent idiopathic scoliosis in Turkey.
AB  - OBJECTIVE: To determine the effectiveness of 3-dimensional therapy in the
      treatment of adolescent idiopathic scoliosis. METHODS: We carried out this study
      with 50 patients whose average age was 14.15 +/-1.69 years at the Physical
      Therapy and Rehabilitation School, Hacettepe University, Ankara, Turkey, from
      1999 to 2004. We treated them as outpatients, 5 days a week, in a 4-hour program
      for the first 6 weeks. After that, they continued with the same program at home.
      We evaluated the Cobb angle, vital capacity and muscle strength of the patients
      before treatment, and after 6 weeks, 6 months and one year, and compared all the
      results. RESULTS: The average Cobb angle, which was 26.10 degrees on average
      before treatment, was 23.45 degrees after 6 weeks, 19.25 degrees after 6 months
      and 17.85 degrees after one year (p<0.01). The vital capacities, which were on
      average 2795 ml before treatment, reached 2956 ml after 6 weeks, 3125 ml after 6
      months and 3215 ml after one year (p<0.01). Similarly, according to the results
      of evaluations after 6 weeks, 6 months and one year, we observed an increase in
      muscle strength and recovery of the postural defects in all patients (p<0.01).
      CONCLUSION: Schroth's technique positively influenced the Cobb angle, vital
      capacity, strength and postural defects in outpatient adolescents.

PMID- 22473140
TI  - Utility of an intervention to detect depression in primary care.
AB  - OBJECTIVE: To determine whether a 3-part intervention consisting of raising
      physicians' awareness of depression, mass depression screening using a 2-item
      version of the Prime MD Questionnaire, and communicating the results of the
      screening to the physician, will improve detection and treatment of depression in
      a primary care setting. METHODS: The study took place in Hilsboro, Oregon between
      July 1, 2001 and September 30, 2001. We distributed educational materials to the
      primary care physicians 2 months before screening patients. Over a 3 month
      period, 3431 consecutive patients who visited Tuality Health Care primary care
      clinics were screened using a 2-item version of the Prime MD depression-screening
      questionnaire. The primary care physicians conducted further assessment for
      certain patients to determine if any screened patient was depressed. We included
      all adult patients who visited Tuality Health Care primary care clinics between
      July 1, 2001 and September 30, 2001 in the study. We excluded patients attending
      the clinic for an emergency and children below 15 years of age. RESULTS: Out of
      3431 subjects initially screened, we included 3290 subjects (96%) in the
      analysis. Of these, 360 subjects (10.9%) were already being treated for
      depression. The median age of the population was 48.5, 63.6% were females, and
      36.4% were males. Physicians were more likely to conduct further assessment for
      depression when the screening result was positive (odds ratio [OR] = 119.13, 95%
      confidence interval [CI]: 81.017-175.17). They were also more likely to make a
      new diagnosis of depression when the screening result was positive (OR = 117.245,
      95% CI: 51.67-266.02). CONCLUSION: The intervention is a useful depression
      screening effort in primary care. We should also consider implementation in other
      primary care settings.

PMID- 22473141
TI  - Indirect effect of electrical stimulation of tibialis anterior on gastro-soleus
      muscles in children with spastic hemiplegic cerebral palsy.
AB  - OBJECTIVE: To investigate the effects of tetanic faradic stimulation in an
      antagonist muscle (tibialis anterior) on agonist muscles (gastro-soleus). In
      addition, to show the effects of maintaining agonist muscle strength on
      antagonist spastic muscle group to improve gait parameters in children with
      spastic hemiplegia. METHODS: We carried out the study at Pamukkale University,
      School of Physical Therapy, Denizli, Turkey between June 2001 and December 2002.
      We included 16 ambulant cerebral palsied children with a mean of age 6.25 +/-
      2.89 years in the study. Each subject practiced a 20-minute electrical
      stimulation session plus neurodevelopmental approach (Bobath Technique) once  a
      day, 4 days a week for 5 weeks. We performed faradic tetanic stimulation to
      stimulate and strengthen the tibialis anterior (antagonist muscle). We performed
      all tests, including goniometric measurement, the Modified Ashworth Scale, and
      gait analysis at the start of the treatment program, after the program, and one
      month after first follow up. RESULTS: After treatment, we found significant
      improvements in goniometric measurements and Modified Ashworth Scale in
      comparison with the baseline measurements (p<0.001). However, the improvements
      did not continue after the first month of treatment (p>0.05). The results of the
      gait analysis showed only a significant difference concerning step width
      (p>0.05). CONCLUSION: The results suggest that tetanic faradic stimulation was
      effective in improving aspects of ankle function, decreasing muscle tone and
      increasing range of motion in children with hemiplegic cerebral palsy during a
      physical therapy program.

PMID- 22473142
TI  - Enterococcus avium. An unusual cause of cerebral abscess.
AB  - Enterococci are responsible for an increasing number of human infections.  They
      are normally part of the flora of the human gastrointestinal tract, buccal
      cavity, perineal skin, vagina, urethra and gallbladder, but may occur as
      pathogens in several sites causing urinary tract infections, intra-abdominal
      infections, fatal bacteremia, meningitis and endocarditis. Enterococcus avium is
      a rare cause of infection in humans. Here, we report a 19-year-old Saudi girl
      diagnosed as a case of astrocytoma grade II arising from the right thalamus. She
      underwent treatment with radiotherapy followed by 5 chemotherapy sessions. She
      subsequently developed a cerebral abscess, and we performed mini craniotomy of
      the left parietal region with drainage of the brain abscess. The pus obtained
      from the abscess grew Enterococcus avium.  We successfully treated her with
      antibiotics and discharged her home. The rarity of the organism causing cerebral
      abscess has motivated the documentation of this case and the pathogenesis of
      Enterococcus avium.

PMID- 22473143
TI  - Novel presenilin 1 mutation associated with early-onset Alzheimer's disease  in 
      a Saudi patient.
AB  - We report a 60-year-old Saudi patient with the clinical diagnosis of Alzheimer's
      disease (AD) and a novel mutation in the presenilin gene. We investigated
      mutations in the presenilin-1 gene in Saudi patients with AD using polymerase
      chain reaction and direct DNA sequencing methods. We extracted genomic DNA from
      the whole blood of both patients and normal control individuals. We sequenced and
      compared amplicons with the sequences of the respective exons of normal
      individuals as well as data available in GenBank. We detected a homozygous
      mutation (g-c) in exon 12, resulting in the missense mutation (Arg377Thr), in the
      DNA of a 60-year-old patient. We located this mutation in the cytoplasmic loop
      near the transmembrane domain 7.

PMID- 22473144
TI  - Hemifacial spasm resulting from vertebral artery dolichoectasia.
AB  - A 32-year-old man presented with left hemifacial spasm. Neurophysiological
      findings revealed an absent ipsilateral R1 on blink reflex. An MRI showed a
      dolichoectatic left vertebral artery impinging on the root exit zone of the left
      facial nerve. Botulinum toxin infections relieved the manifestations of
      hemifacial spasm. This case demonstrates that MRI/MRA is an essential part of the
      work-up for hemifacial spasm, and shows that in accordance with the literature,
      vertebral dolichoectasia is an uncommon cause of hemifacial spasm.

PMID- 22473145
TI  - Schwannoma of the vestibulocochlear nerve presenting as isolated paroxysmal
      vertigo.
AB  - We report a patient with a schwannoma of the eighth cranial (vestibulocochlear)
      nerve who presented with isolated episodes of paroxysmal vertigo and positive Dix
      Hallpike maneuver, and without the common features of hearing loss,
      disequilibrium and tinnitus. There are no previous reports of paroxysmal episodes
      of vertigo as the sole manifestation of schwannoma of the vestibulocochlear
      nerve. Hence, recurrent paroxysmal vertigo should therefore prompt the physician
      to rule out schwannoma of the vestibulocochlear nerve as a potential cause even
      in the presence of normal hearing tests.

PMID- 22473146
TI  - Asymptomatic pons tuberculoma in an infant with miliary tuberculosis.
AB  - Miliary tuberculosis is caused by the hematogenous spread of Mycobacterium
      tuberculosis and consists of 1.5% of all tuberculosis cases. It is seen mostly in
      infants because of the immature immune system, and central nervous system (CNS)
      involvement is not rare. Tuberculomas are rarely seen in the localized form of
      CNS tuberculosis, and only 4% are localized in the brain stem. We report a 4.5
      month-old infant who deteriorated during follow-up with the diagnosis of
      cytomegalovirus pneumonia, and afterwards received the diagnosis of miliary
      tuberculosis. Although the baby had no neurologic abnormality and cerebrospinal
      fluid findings were normal, cranial MRI revealed contrast enhanced nodular
      lesions in pons, cerebellum, and right parietal region. The case is presented to
      intensify the importance of CNS investigation even if the patient with miliary
      tuberculosis has no neurologic finding.

PMID- 22473147
TI  - Anorexia nervosa. Emphasis on its medical complications.
AB  - Anorexia nervosa (AN) is a well-recognized heterogeneous psychiatric disorder,
      associated with high morbidity and mortality with several medical complications.
      Besides a brief review, this paper also reports on a single female patient with
      AN. Eating disorders are reported to be slightly more common among western
      cultures, but developing countries are not immune to eating disorders. This
      patient showed both the psychopathology of abnormal eating behavior and serious
      physical complications and despite all possible treatment interventions, she
      ultimately died. We discuss different aspects of AN including the importance of
      constant social support from key relatives.

PMID- 22473148
TI  - Alzheimer's disease and oral health.

PMID- 22473149
TI  - Acute kidney injury and mortality in hospitalized patients.
AB  - BACKGROUND: The objective of this study was to determine the incidence of acute
      kidney injury (AKI) and its relation with mortality among hospitalized patients.
      METHODS: Analysis of hospital discharge and laboratory data from an urban
      academic medical center over a 1-year period. We included hospitalized adult
      patients receiving two or more serum creatinine (sCr) measurements. We excluded
      prisoners, psychiatry, labor and delivery, and transferred patients, 'bedded
      outpatients' as well as individuals with a history of kidney transplant or
      chronic dialysis. We defined AKI as (a) an increase in sCr of >=0.3 mg/dl; (b) an
      increase in sCr to >=150% of baseline, or (c) the initiation of dialysis in a
      patient with no known history of prior dialysis. We identified factors associated
      with AKI as well as the relationships between AKI and in-hospital mortality.
      RESULTS: Among the 19,249 hospitalizations included in the analysis, the
      incidence of AKI was 22.7%. Older persons, Blacks, and patients with reduced
      baseline kidney function were more likely to develop AKI (all p < 0.001). Among
      AKI cases, the most common primary admitting diagnosis groups were circulatory
      diseases (25.4%) and infection (16.4%). After adjustment for age, sex, race,
      admitting sCr concentration, and the severity of illness index, AKI was
      independently associated with in-hospital mortality (adjusted odds ratio 4.43,
      95% confidence interval 3.68-5.35). CONCLUSIONS: AKI occurred in over 1 of 5
      hospitalizations and was associated with a more than fourfold increased
      likelihood of death. These observations highlight the importance of AKI
      recognition as well as the association of AKI with mortality in hospitalized
      patients.

PMID- 22473150
TI  - Familial Williams-Beuren syndrome ascertained by screening rather than targeted
      diagnosis.
AB  - Williams-Beuren syndrome (WBS), a contiguous gene deletion syndrome, mostly
      occurs sporadically. Although a few cases of familial WBS have been reported in
      the literature, molecular confirmation of the deletion has not been carried out
      in all of them. Here, we report on the eighth clinically and molecularly
      confirmed inherited WBS detected in a family with 'familial mental retardation.'
      A comprehensive screening approach to mental retardation that included stepwise
      karyotyping, assessment for fragile-X syndrome, subtelomeric rearrangements and
      known microdeletion/microduplication syndromes, and a genome-wide array-CGH study
      was applied. The father, the mother, and their daughter were all mentally
      handicapped with nonspecific clinical manifestations and dysmorphic features. The
      first child of the family died from multiple congenital anomalies. The father and
      his daughter, who had never been suspected to have WBS, were diagnosed as having
      a deletion of the WBS critical region. No other abnormalities were detected in
      the family. Unlike other previously reported cases, in which the disease was
      ascertained on the basis of clinical manifestations, the present report
      represents an example of the detection of cryptic chromosomal abnormalities in
      mental retardation patients by the stepwise application of high-throughput
      screening methods.

PMID- 22473151
TI  - Homozygous nonsense mutation in HOXD13 underlies synpolydactyly with a cleft.

PMID- 22473152
TI  - Unusual neuroradiological features in Schinzel-Giedion syndrome:  a novel case.

PMID- 22473153
TI  - Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma.
AB  - PURPOSE: The prognosis of acute- and lymphoma-type adult T-cell leukemia/lymphoma
      (ATL) is poor, but there is marked diversity in survival outcomes. The aim of
      this study was to develop a prognostic index (PI) for acute- and lymphoma-type
      ATL (ATL-PI). PATIENTS AND METHODS: In a retrospective review, data from 807
      patients newly diagnosed with acute- and lymphoma-type ATL between January 2000
      and May 2009 were evaluated. We randomly divided subjects into training (n = 404)
      and validation (n = 403) samples, and developed a PI using a multivariable
      fractional polynomial model. RESULTS: Median overall survival time (MST) for the
      807 patients was 7.7 months. The Ann Arbor stage (I and II v III and IV),
      performance status (0 to 1 v 2 to 4), and three continuous variables (age, serum
      albumin, and soluble interleukin-2 receptor [sIL-2R]) were identified as
      independent prognostic factors in the training sample. Using these variables, a
      prognostic model was devised to identify different levels of risk. In the
      validation sample, MSTs were 3.6, 7.3, and 16.2 months for patients at high,
      intermediate, and low risk, respectively (P < .001; chi(2) = 89.7, 2 df; log-rank
      test). We also simplified the original ATL-PI according to dichotomizing age at
      70 years, serum albumin at 3.5 g/dL, and sIL-2R at 20,000 U/mL and developed an
      easily calculable PI with prognostic discrimination power (P < .001; chi(2) =
      74.2, 2 df; log-rank test). CONCLUSION: The ATL-PI is a promising new tool for
      identifying patients with acute- and lymphoma-type ATL at different risks.

PMID- 22473154
TI  - Getting to the heart of the matter.

PMID- 22473156
TI  - Public health and the tanning bed controversy.

PMID- 22473155
TI  - Phase III trial of cetuximab with continuous or intermittent fluorouracil,
      leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line
      treatment of metastatic colorectal cancer: the NORDIC-VII study.
AB  - PURPOSE: The NORDIC-VII multicenter phase III trial investigated the efficacy of
      cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic
      FLOX), administered continuously or intermittently, in previously untreated
      metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on
      treatment outcome was also investigated. PATIENTS AND METHODS: Patients were
      randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and
      FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end
      point was progression-free survival (PFS). Overall survival (OS), response rate,
      R0 resection rate, and safety were secondary end points. RESULTS: Of the 571
      patients randomly assigned, 566 were evaluable in intention-to-treat (ITT)
      analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457
      patients (81%), respectively. KRAS mutations were present in 39% of the tumors;
      12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong
      negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and
      7.3 months for the three arms, respectively (not significantly different). OS was
      almost identical for the three groups (20.4, 19.7, 20.3 months, respectively),
      and confirmed response rates were 41%, 49%, and 47%, respectively. In patients
      with KRAS wild-type tumors, cetuximab did not provide any additional benefit
      compared with FLOX alone. In patients with KRAS mutations, no significant
      difference was detected, although a trend toward improved PFS was observed in arm
      B. The regimens were well tolerated. CONCLUSION: Cetuximab did not add
      significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.

PMID- 22473157
TI  - Influence of major postoperative complications on health-related quality of life
      among long-term survivors of esophageal cancer surgery.
AB  - PURPOSE: To evaluate the effect of major postoperative complications on health
      related quality of life (HRQL) in 5-year survivors of esophageal cancer surgery.
      PATIENTS AND METHODS: This study was based on the Swedish Esophageal and Cardia
      Cancer register with almost complete nationwide coverage and data on esophageal
      cancer surgery collected prospectively between 2001 and 2005. Patients who were
      alive 5 years after surgery were eligible. HRQL was assessed longitudinally until
      5 years after surgery by using the validated European Organisation for Research
      and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and OES18.
      Linear mixed models were used to assess the mean score difference (MD) with 95%
      CIs of each aspect of HRQL in patients with or without major postoperative
      complications. Adjustment was made for several potential confounders. RESULTS: Of
      153 patients who survived 5 years, 141 patients (92%) answered the 5-year HRQL
      questionnaires. Of these individuals, 46 patients (33%) sustained a major
      postoperative complication. Dyspnea (MD, 15; 95% CI, 6 to 23), fatigue (MD, 13;
      95% CI, 5 to 20), and eating restrictions (MD, 10; 95% CI, 2 to 17) were
      clinically and statistically significantly deteriorated throughout the follow-up
      in patients with major postoperative complications compared with patients without
      major complications. Although problems with choking declined to levels comparable
      with patients without major postoperative complications, sleep difficulties and
      gastroesophageal reflux progressively worsened during follow-up. CONCLUSION: The
      occurrence of postoperative complications exerts a long-lasting negative effect
      on HRQL in patients who survive 5 years after esophagectomy for cancer.

PMID- 22473158
TI  - Is the pooled analysis of the north central cancer treatment group phase III
      trials N9741 and N9841 biased?

PMID- 22473160
TI  - Explaining the unexplainable: EGFR antibodies in colorectal cancer.

PMID- 22473159
TI  - Intensive care unit outcomes among patients with lung cancer in the surveillance,
      epidemiology, and end results-medicare registry.
AB  - PURPOSE: Lung cancer is the leading cause of cancer-related mortality. Intensive
      care unit (ICU) use among patients with cancer is increasing, but data regarding
      ICU outcomes for patients with lung cancer are limited. PATIENTS AND METHODS: We
      used the Surveillance, Epidemiology, and End Results (SEER) -Medicare registry
      (1992 to 2007) to conduct a retrospective cohort study of patients with lung
      cancer who were admitted to an ICU for reasons other than surgical resection of
      their tumor. We used logistic and Cox regression to evaluate associations of
      patient characteristics and hospital mortality and 6-month mortality,
      respectively. We calculated adjusted associations for mechanical ventilation
      receipt with hospital and 6-month mortality. RESULTS: Of the 49,373 patients with
      lung cancer admitted to an ICU for reasons other than surgical resection, 76% of
      patients survived the hospitalization, and 35% of patients were alive 6 months
      after discharge. Receipt of mechanical ventilation was associated with increased
      hospital mortality (adjusted odds ratio, 6.95; 95% CI, 6.89 to 7.01; P < .001),
      and only 15% of these patients were alive 6 months after discharge. Of all ICU
      patients with lung cancer, the percentage of patients who survived 6 months from
      discharge was 36% for patients diagnosed in 1992 and 32% for patients diagnosed
      in 2005, whereas it was 16% and 11% for patients who received mechanical
      ventilation, respectively. CONCLUSION: Most patients with lung cancer enrolled in
      Medicare who are admitted to an ICU die within 6 months of admission. To improve
      patient-centered care, these results should guide shared decision making between
      patients with lung cancer and their clinicians before an ICU admission.

PMID- 22473161
TI  - High risk of symptomatic cardiac events in childhood cancer survivors.
AB  - PURPOSE: To evaluate the long-term risk for validated symptomatic cardiac events
      (CEs) and associated risk factors in childhood cancer survivors (CCSs). PATIENTS
      AND METHODS: We determined CEs grade 3 or higher: congestive heart failure (CHF),
      cardiac ischemia, valvular disease, arrhythmia and/or pericarditis (according to
      Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) in a
      hospital-based cohort of 1,362 5-year CCSs diagnosed between 1966 and 1996. We
      calculated both marginal and cause-specific cumulative incidence of CEs and cause
      specific cumulative incidence of separate events. We analyzed different risk
      factors in multivariable Cox regression models. RESULTS: Overall, 50 CEs,
      including 27 cases of CHF, were observed in 42 survivors (at a median attained
      age of 27.1 years). The 30-year cause-specific cumulative incidence of CEs was
      significantly increased after treatment with both anthracyclines and cardiac
      irradiation (12.6%; 95% CI, 4.3% to 20.3%), after anthracyclines (7.3%; 95% CI,
      3.8% to 10.7%), and after cardiac irradiation (4.0%; 95% CI, 0.5% to 7.4%)
      compared with other treatments. In the proportional hazards analyses,
      anthracycline (dose), cardiac irradiation (dose), combination of these
      treatments, and congenital heart disease were significantly associated with
      developing a CE. We demonstrated an exponential relationship between the
      cumulative anthracycline dose, cardiac irradiation dose, and risk of CE.
      CONCLUSION: CCSs have a high risk of developing symptomatic CEs at an early age.
      The most common CE was CHF. Survivors treated with both anthracyclines and
      radiotherapy have the highest risk; after 30 years, one in eight will develop
      severe heart disease. The use of potentially cardiotoxic treatments should be
      reconsidered for high-risk groups, and frequent follow-up for high-risk survivors
      is needed.

PMID- 22473162
TI  - Outcome of acute promyelocytic leukemia (APL) in children and adolescents: an
      analysis in two consecutive trials of the European APL Group.
AB  - PURPOSE: Acute promyelocytic leukemia (APL) is rare in children. All-trans
      retinoic acid (ATRA) combined with chemotherapy, the reference treatment of APL,
      is generally considered to produce similar results in children and adults.
      However, previously published childhood APL studies have generally analyzed all
      patients age < 18 years as a group, without further dividing according to age.
      PATIENTS AND METHODS: We compared disease characteristics and outcomes of
      children (age <= 12 years), adolescents (13 to 18 years), and adults (> 18 years)
      included in two multicenter APL clinical trials (APL 93 and 2000 trials).
      RESULTS: Of the 833 patients age <= 60 years included in the two trials, 26 (3%),
      58 (7%), and 749 (90%) were children, adolescents, and adults, respectively.
      Children had significantly higher baseline WBC counts (P < .001). The complete
      remission (CR) rate (92%, 100%, and 94.5%, respectively) and 5-year cumulative
      incidence of relapse (CIR; 28%, 20%, and 23%, respectively) did not differ
      between children, adolescents, and adults, whereas adolescents had significantly
      better overall survival (OS; 5-year OS, 93.6% v 80.4% in adults and 80.4% in
      children; P = .03). However, in children age <= 4 years, the 5-year CIR was 52%,
      compared with 17.6% in children age 5 to 12 years (P = .006), although most of
      the younger children who relapsed experienced durable salvage with autologous or
      allogeneic stem-cell transplantation. CONCLUSION: Adolescents and children age >
      4 years with APL treated with ATRA and chemotherapy have outcomes at least as
      favorable as those of adults. Younger children seem to experience more relapses
      and may require reinforcement of first-line treatment.

PMID- 22473164
TI  - Kairos.

PMID- 22473163
TI  - Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin,
      capecitabine, and preoperative radiotherapy with or without cetuximab followed by
      total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C).
AB  - PURPOSE: To evaluate the addition of cetuximab to neoadjuvant chemotherapy before
      chemoradiotherapy in high-risk rectal cancer. PATIENTS AND METHODS: Patients with
      operable magnetic resonance imaging-defined high-risk rectal cancer received four
      cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine
      chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen
      plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR;
      pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients
      with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response
      (RR), progression-free survival (PFS), overall survival (OS), and safety in the
      wild-type and overall populations and a molecular biomarker analysis. RESULTS:
      One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of
      149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n =
      46), and in these patients, the addition of cetuximab did not improve the primary
      end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS
      (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v
      CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after
      chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034).
      Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. CONCLUSION:
      Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF
      wild-type rectal cancer, but the primary end point of improved CR was not met.

PMID- 22473165
TI  - Relapsed seminoma during surveillance: first treatment choice should be
      radiotherapy.

PMID- 22473166
TI  - Follow-up of breast cancer survivors.

PMID- 22473167
TI  - Appropriate chemotherapy dosing for obese adult patients with cancer: American
      Society of Clinical Oncology clinical practice guideline.
AB  - PURPOSE: To provide recommendations for appropriate cytotoxic chemotherapy dosing
      for obese adult patients with cancer. METHODS: The American Society of Clinical
      Oncology convened a Panel of experts in medical and gynecologic oncology,
      clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics
      and a patient representative. MEDLINE searches identified studies published in
      English between 1996 and 2010, and a systematic review of the literature was
      conducted. A majority of studies involved breast, ovarian, colon, and lung
      cancers. This guideline does not address dosing for novel targeted agents.
      RESULTS: Practice pattern studies demonstrate that up to 40% of obese patients
      receive limited chemotherapy doses that are not based on actual body weight.
      Concerns about toxicity or overdosing in obese patients with cancer, based on the
      use of actual body weight, are unfounded. RECOMMENDATIONS: The Panel recommends
      that full weight-based cytotoxic chemotherapy doses be used to treat obese
      patients with cancer, particularly when the goal of treatment is cure. There is
      no evidence that short- or long-term toxicity is increased among obese patients
      receiving full weight-based doses. Most data indicate that myelosuppression is
      the same or less pronounced among the obese than the non-obese who are
      administered full weight-based doses. Clinicians should respond to all treatment
      related toxicities in obese patients in the same ways they do for non-obese
      patients. The use of fixed-dose chemotherapy is rarely justified, but the Panel
      does recommend fixed dosing for a few select agents. The Panel recommends further
      research into the role of pharmacokinetics and pharmacogenetics to guide
      appropriate dosing of obese patients with cancer.

PMID- 22473168
TI  - Cyclooxygenase-2 (COX-2) as a predictive marker for the use of COX-2 inhibitors
      in advanced non-small-cell lung cancer.

PMID- 22473169
TI  - Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small
      cell lung cancer: the COCIS meta-analysis of individual patient data.
AB  - PURPOSE: Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy
      in the first-line treatment of small-cell lung cancer (SCLC) remains contentious,
      a meta-analysis of individual patient data was performed to compare the two
      treatments. PATIENTS AND METHODS: A systematic review identified randomized
      trials comparing cisplatin with carboplatin in the first-line treatment of SCLC.
      Individual patient data were obtained from coordinating centers of all eligible
      trials. The primary end point was overall survival (OS). All statistical analyses
      were stratified by trial. Secondary end points were progression-free survival
      (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves
      were compared by using the log-rank test. ORR was compared by using the Mantel
      Haenszel test. RESULTS: Four eligible trials with 663 patients (328 assigned to
      cisplatin and 335 to carboplatin) were included in the analysis. Median OS was
      9.6 months for cisplatin and 9.4 months for carboplatin (hazard ratio [HR], 1.08;
      95% CI, 0.92 to 1.27; P = .37). There was no evidence of treatment difference
      between the cisplatin and carboplatin arms according to sex, stage, performance
      status, or age. Median PFS was 5.5 and 5.3 months for cisplatin and carboplatin,
      respectively (HR, 1.10; 95% CI, 0.94 to 1.29; P = .25). ORR was 67.1% and 66.0%,
      respectively (relative risk, 0.98; 95% CI, 0.84 to 1.16; P = .83). Toxicity
      profile was significantly different for each of the arms: hematologic toxicity
      was higher with carboplatin, and nonhematologic toxicity was higher with
      cisplatin. CONCLUSION: Our meta-analysis of individual patient data suggests no
      differences in efficacy between cisplatin and carboplatin in the first-line
      treatment of SCLC, but there are differences in the toxicity profile.

PMID- 22473170
TI  - Understanding optimal colonic cancer surgery: comparison of Japanese D3 resection
      and European complete mesocolic excision with central vascular ligation.
AB  - PURPOSE: Over recent years, patient outcomes after colon cancer resection have
      not improved to the same degree as for rectal cancer. Japanese D3 resection and
      European complete mesocolic excision (CME) with central vascular ligation (CVL)
      are both based on sound oncologic principles. Expert surgeons using both
      techniques report impressive outcomes as compared with standard surgery. We aimed
      to independently compare the physical appearances and quality of specimens
      resected using both techniques in major institutions in Japan and Germany.
      METHODS: A series of resections for primary colon cancer from one European and
      two Japanese centers were independently assessed in terms of the plane of
      surgery, physical characteristics, and lymph node yields. RESULTS: Mesocolic
      plane resection rates from both series were high; however, Japanese D3 specimens
      were significantly shorter (162 v 324 mm, P < .001), resulting in a smaller
      amount of mesentery (8,309 v 17,957 mm(2), P < .001) and nodal yield (median, 18
      v 32, P < .001). The distance from the high vascular tie to the bowel wall (100 v
      99 mm, P = .605) was equivalent. CONCLUSION: Both techniques showed high
      mesocolic plane resection rates and long distances between the high tie and the
      bowel wall. The extended longitudinal resection after CME with CVL increased the
      nodal yield but did not increase the number of tumor involved nodes. Both series
      were oncologically superior to recently reported series from other countries and
      confirm the wide variation in colonic cancer surgery and the need for further
      standardization and optimization following the approach undertaken in improving
      rectal cancer outcomes.

PMID- 22473171
TI  - Defining quality in colon cancer surgery.

PMID- 22473173
TI  - Isolating intrinsic noise sources in a stochastic genetic switch.
AB  - The stochastic mutual repressor model is analysed using perturbation methods.
      This simple model of a gene circuit consists of two genes and three promotor
      states. Either of the two protein products can dimerize, forming a repressor
      molecule that binds to the promotor of the other gene. When the repressor is
      bound to a promotor, the corresponding gene is not transcribed and no protein is
      produced. Either one of the promotors can be repressed at any given time or both
      can be unrepressed, leaving three possible promotor states. This model is
      analysed in its bistable regime in which the deterministic limit exhibits two
      stable fixed points and an unstable saddle, and the case of small noise is
      considered. On small timescales, the stochastic process fluctuates near one of
      the stable fixed points, and on large timescales, a metastable transition can
      occur, where fluctuations drive the system past the unstable saddle to the other
      stable fixed point. To explore how different intrinsic noise sources affect these
      transitions, fluctuations in protein production and degradation are eliminated,
      leaving fluctuations in the promotor state as the only source of noise in the
      system. The process without protein noise is then compared to the process with
      weak protein noise using perturbation methods and Monte Carlo simulations. It is
      found that some significant differences in the random process emerge when the
      intrinsic noise source is removed.

PMID- 22473174
TI  - Variations of clinical SPECT/CT operations: an international survey.
AB  - AIM: This survey gathers information about clinical SPECT/CT operations worldwide
      to help guide standardization of clinical SPECT/CT imaging. METHODS: An
      international, web-based survey of SPECT/CT users was initiated in 12/2010
      through an e-mail distribution. Users were asked 71 questions related to (A)
      demographics, (B) SPECT/CT operations/utilization and (C) variations in imaging
      protocols. RESULTS: Collected responses originated from 117 imaging centers in
      the Americas (66%), Europe (20%), Asia-Pacific (11%) and the Middle-East (3%),
      with the majority of responding sites representing public health care
      institutions (69%). Most sites operate 1-2 SPECT/CT-systems (74%), typically
      installed in Nuclear Medicine departments (84%) with extensive prior SPECT-only
      experience (82%). Only 14% of SPECT/CTs are installed in Radiology departments.
      Clinical SPECT/CT imaging is performed either as routine (51%) or ad-hoc "add-on"
      procedure (49%) with a high inter-site and inter-examination variability. The
      main application of the integrated CT is to provide anatomical localization of
      the tracer uptake rather than to produce contrast-enhanced or other high-quality
      CT images. Consequently, in only 22% of the sites a CT contrast injector is
      installed. Only 6% of centers use SPECT/CT devices for stand-alone CT procedures.
      CONCLUSION: An international survey among clinical SPECT/CT users revealed that
      SPECT/CT is a not a routine component of nuclear medicine procedures. The
      majority of the centers responding do not fully utilize the diagnostic potential
      of the CT components. Significant variations in standard imaging protocols were
      observed. These findings illustrate the need for training and standardization and
      underscore the need for revisiting the role of SPECT/CT in diagnostic imaging.

PMID- 22473175
TI  - Probing Interactions between Aggrecan and Mica Surface by the Atomic Force
      Microscopy.
AB  - Aggrecan is a bottlebrush shaped macromolecule found in the extracellular matrix
      of cartilage. The negatively charged glycosaminoglycan (GAG) chains attached to
      its protein backbone give aggrecan molecules a high charge density, which is
      essential for exerting high osmotic swelling pressure and resisting compression
      under external load. In solution aggrecan assemblies are insensitive to the
      presence of calcium ions, and show distinct osmotic pressure versus concentration
      regimes. The aim of this study is to investigate the effect of ionic environment
      on the structure of aggrecan molecules adsorbed onto well-controlled mica
      surfaces. The conformation of the aggrecan were visualized using Atomic Force
      Microscopy. On positively charged APS mica the GAG chains of the aggrecan
      molecules are distinguishable, and their average dimensions are practically
      unaffected by the presence of salt ions. With increasing aggrecan concentration
      they form clusters, and at higher concentrations they form a continuous monolayer
      of conforming molecules. On negatively charged mica, the extent of aggrecan
      adsorption varies with salt composition. Understanding aggrecan adsorption onto a
      charged surface provides insight into its interactions with bone and implant
      surfaces in the biological milieu.

PMID- 22473177
TI  - Myasthenia gravis from Thomas Willis to the present.
AB  - The history of the development of knowledge of myasthenia gravis is reviewed. 
      Clinical profiles of the immune and non-immune mediated forms of myasthenia are
      discussed.  The current theory of pathogenesis is reviewed.  Tests used to
      diagnose myasthenia gravis, and their comparative diagnostic yields are
      presented.  Past and current modalities of treatment are reviewed.  Future
      therapeutic strategies are introduced.  The roles of the thymus and thymectomy in
      the genesis and treatment of myasthenia gravis are discussed.

PMID- 22473176
TI  - Selective turn-on fluorescent probes for imaging hydrogen sulfide in living
      cells.
AB  - Hydrogen sulfide (H(2)S) is an important biological messenger but few
      biologically-compatible methods are available for its detection. Here we report
      two bright fluorescent probes that are selective for H(2)S over cysteine,
      glutathione and other reactive sulfur, nitrogen, and oxygen species. Both probes
      are demonstrated to detect H(2)S in live cells.

PMID- 22473178
TI  - Febrile seizures. From molecular biology to clinical practice.
AB  - Febrile seizures occur between the age of 3 months and 5 years with a temperature
      of 38 degrees C or higher, and are either simple or complex. Eight gene loci have
      been identified to be associated with certain cases of autosomal dominant
      familial febrile seizures, and 12 genes have been associated with some of the
      familial epilepsy syndromes that can start with febrile seizures. The mutations
      and the protein products are known for only some of these 20 genes. The risk of
      recurrence of convulsions in a further febrile illness is on average 30%, and of
      developing epilepsy is on average 6%, but both vary depending on the presence and
      number of risk factors in any given patient. The immediate treatment of a febrile
      convulsion is intravenous or rectal diazepam, but febrile status epilepticus
      requires intravenous Phenobarbital and possibly other medications. Long-term
      antiepileptic drugs are not recommended in most patients with febrile seizures.
      However, exceptions should be considered on an individual basis in patients with
      complex febrile seizures with multiple risk factors for development of later
      epilepsy.

PMID- 22473179
TI  - The role of vitamin E in the prevention of coronary events and stroke. Meta
      analysis of randomized controlled trials.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in
      the world. Vitamin E as an anti-oxidant vitamin, was suggested to have a role in
      the prevention of CVD.   We did a meta-analysis, using the Cochrane Group
      Methodology, of all available randomized controlled trials (RCTs) to evaluate the
      role of vitamin E in the prevention of CVD.  Nine studies met inclusion criteria,
      including 80,645 participants.  Vitamin E supplementation was not associated with
      a reduction in total mortality or total CVD mortality, but it was associated with
      a small statistically significant reduction in non-fatal myocardial infarction in
      patients with pre-existing coronary artery disease.  Prophylactic use of vitamin
      E in doses ranging between 50-800 IU was not associated with any increase in the
      incidence of serious side effects.

PMID- 22473180
TI  - Clinical profile of admitted children with febrile seizures.
AB  - OBJECTIVE: The objectives of this study were to evaluate the clinical profile,
      investigations, treatments and outcome of hospitalized children with febrile
      seizures. METHODS: A series of 69 consecutive children with febrile seizures was
      identified by chart review from 1st January 1997 to 1st January 2002 at King
      Abdul-Aziz University Hospital in Jeddah, Kingdom of Saudi Arabia. Clinical,
      laboratory, EEG, and neuroimaging data were evaluated by one investigator using a
      structured data collection form. RESULTS: The children's ages ranged between 7-70
      months (mean 20, SD 14), and 59.5% were males. The source of the febrile illness
      was evident in 65%, however, most admitted children (60 out of 69) had atypical
      seizures (55%), were ill looking (24.5%), had febrile status (17.5%), or positive
      meningeal irritation signs (4%). Electrolyte abnormalities were uncommon (10%),
      however, complete blood count was abnormal in 45%, which increased the likelihood
      of receiving intravenous antibiotics (p=0.01). Lumbar puncture was performed on
      75%, particularly those with a first seizure (odds ratio [OR] 3.8, 95% confidence
      interval [CI] 0.9-15) or younger than 2 years of age (OR 3.4, 95% CI 0.7-17).
      Brain CT was performed in 13% and EEG in 33%. Obtaining an EEG was less likely if
      the seizures were typical (13% versus 50% in atypical, p=0.002). Duration of
      hospitalization ranged between 1-14 days (mean 4.7, SD 3.2), and only one child
      had meningitis, which was predicted clinically. CONCLUSION: Pediatricians are
      selective in admitting and investigating children with febrile seizures. The
      children frequently had atypical seizures, status epilepticus, or were ill
      looking. The yield of investigations remains low and does not justify extensive
      work-up or prolonged hospitalization.

PMID- 22473181
TI  - Effects of infant crawling experience on range of motion.
AB  - OBJECTIVE: The purpose of this study was to show the effects of infant crawling
      experience on shoulder and hip range of motion and trunk flexibility. METHODS:
      One hundred and twenty children who had  attended the Child and Mothers Health
      Center in Kutahya City of Turkey between 2002 and 2003 were evaluated, and 40
      children walking without assistance with normal motor development were divided
      into 2 groups, crawler group (CG) (N:20) and noncrawler group (NCG) (N:20). The
      CG children were selected to match with age of the NCG. Shoulder and hip range of
      motion and trunk flexibility were measured for assessment. RESULTS: No
      statistical differences were observed in all physical characteristics and range
      of movement (ROM) for girls and boys of each group (p>0.05). The CG girls were
      statistically found heavier and taller than NCG (p<0.05). The CG were found to
      start to walk later (p<0.05) and used walker devices less often (p<0.01) than the
      NCG. All hip ROM values were found statistically higher in NCG than CG (p<0.05,
      p<0.01) except hip flexion (p>0.05) and no statistical differences were found
      between groups shoulder ROM values (p>0.05), except NCG left flexion (p<0.05).
      The highest hip abduction ROM was measured in NCG boys and highest external
      rotation was measured in NCG girls. No statistical differences were found in
      trunk flexion and sit and reach test in both groups. CONCLUSION: Crawling is an
      important developmental exercise for infants to gain joint stabilization
      especially on the hip joint, and parents should facilitate their infant's to
      crawl and maintain suitable environmental conditions.

PMID- 22473182
TI  - The Bell's phenomenon in newborns.
AB  - OBJECTIVE: This study was undertaken to detect the course of Bell's phenomenon
      development in full and pre-term babies. METHODS: Three hundred healthy newborns
      (150 full term and 150 pre-term) born at Prince Rashid Bin Al-Hasan military
      hospital from the first of January 2000 to 31st of December 2000 in Irbid in the
      north of Jordan, were randomly selected and included in the study. Bell's
      phenomenon response was graded according to the movement of the eye as: 0 = no
      movement, 1 = minimal movement (the pupil still visible), 2 = full movement (the
      pupil is covered by the eyelid). The Bell's Phenomenon Scoring System (BPSS) was
      chosen to score the eye movement. The newborn was examined during the first week
      of life and then repeated at 4 weekly intervals, for 5 months for the full term
      babies and for 2 months for the pre-term babies. RESULTS: In the full term group
      only 25/150 (16.7%) of the newborns showed full response (BPSS-2) during the
      first week of life and this number increased to 133/150 (88.7%) at the age of 5
      months. None of the pre-term group showed the Bell's phenomenon response (BPSS-0)
      during the first week of life and only 21/150 (14%) had full response (BPSS-2) at
      4 weeks. At the age of 2 months approximately 51/150 (34%) developed full
      response (BPSS-2). CONCLUSION: The development of Bell's phenomenon reflex
      reflects the maturation process of the brainstem and the extraocular muscles
      related to eye elevation. It should be considered as part of the routine tests
      undertaken by every pediatrician and ophthalmologist during the neuro-ophthalmic
      examination in newborns.

PMID- 22473183
TI  - Anesthesia and perioperative care of newborns with obstetrical brachial plexus
      injuries.
AB  - OBJECTIVE: The perioperative period is a particularly dangerous time for babies
      with serious obstetrical brachial plexus injuries undergoing microsurgical
      reconstruction. The aim of this study was to evaluate the perioperative and early
      postoperative problems in these patients. METHODS: Anesthetic management and pre
      and postoperative medical records were retrospectively reviewed for infants who
      underwent microsurgical nerve reconstruction (n=46) at the Hacettepe University,
      Ankara, Turkey from 1995 to 2003. RESULTS: Anesthetic considerations include the
      positioning, long duration of operation, fluid administration,  intra and
      postoperative fever, tachycardia and respiratory complications. CONCLUSION:
      Respiratory management and fluid administration are the most important factors in
      anesthesia for brachial injuries.  Care must also be taken for the long duration
      of the surgery, temperature, and loss of airway.

PMID- 22473184
TI  - Altered oxytocin and vasopressin levels in autistic children in Central Saudi
      Arabia.
AB  - OBJECTIVE: The aim of the current study is to assess plasma levels of oxytocin
      and vasopressin in autistic children. Also, to correlate plasma levels of those
      neuropeptides to the degree of autism and age of the affected child. An
      additional aim is to investigate the role of Pitocin induction in the genesis of
      autism. METHODS: The study was conducted in Riyadh, Kingdom of Saudi Arabia
      between September 2003 and April 2004. Seventy-seven autistic child from Riyadh
      area participated in the study, with the confirmed diagnosis according to DSM-IV
      diagnostic criteria of autism. The parents/guardians filled a simple related
      questionnaire, then plasma oxytocin and vasopressin levels were measured in
      autistic and control children. RESULTS: Results showed a statistically
      significant lower plasma level of oxytocin and vasopressin in autistic children
      as compared to controls. There was no significant correlation between the degree
      of autism, or the age of the affected child and plasma levels of oxytocin or
      vasopressin. There was a higher incidence of Pitocin-induced labor among
      autistics as compared to normal. CONCLUSION: Data in this study prove that
      oxytocin and vasopressin plasma levels were reduced in autistic children which,
      might be related to abnormal social behavior in autistic children. Higher rates
      of Pitocin induction were found among the autistic group. The data supports an
      association between exogenous exposure to oxytocin and neurodevelopmental
      abnormalities. Further clinical studies are recommended to explore the possible
      therapeutic effects of oxytocin and vasopressin in autism.

PMID- 22473185
TI  - Prevalence of neuropathic pain among patients suffering from chronic low back
      pain in Saudi Arabia.
AB  - OBJECTIVE: The aim of this study was to assess the prevalence of neuropathic pain
      among patients suffering from chronic low back pain using the Leeds assessment of
      neuropathic symptoms and signs (LANSS) pain scale. METHODS: This was a pilot
      study collected from 10 centers in the Middle East Region, with each center
      enrolling 10 patients between November 2004 and January 2004.  In total, 100
      patients with chronic low back pain were included in the study. The LANSS
      clinical assessment score was used to assess the presence of neuropathic pain.
      Patients with score >12 were considered to have neuropathic pain, while patients
      with score a < 12 were considered as having nociceptive pain. RESULTS: We found
      that 41% of the chronic low back pain patients had neuropathic pain and 59% had
      nociceptive pain. CONCLUSION: The ability to identify neuropathic pain mechanisms
      should lead to individualized treatment resulting in improved pain control in
      this group of patients with chronic low back pain.

PMID- 22473186
TI  - Transient ischemic attack and ischemic stroke, risk factors and preventive roles
      of the first contact physicians.
AB  - OBJECTIVE: This study had been designed to find the relative frequency of each of
      ischemic stroke's risk factors and to evaluate the action of the first contact
      physician for transient ischemic attack (TIA) cases. METHODS: This study is a
      cross sectional study that enrolled 100 randomly selected patients with clinical
      and radiological diagnosis of ischemic stroke, who had attended Al-Yarmouk
      Teaching Hospital, Baghdad, Iraq during the period between the 1st of January
      2002 and the 1st of July 2002. RESULTS: The patients' age range was 40-79 years
      old (mean 63.57 years, SD 8.31, coefficient of variation 0.31). Forty-four
      patients (44%) were smokers, 34 patients (34%) were hypertensive, and 28 patients
      (28%) were diabetics. Of those under the age of 55, 78.6% had 2 or more risk
      factors. Positive history of TIA was observed in 28 patients (28%), 64.3% of whom
      (18 patients) had consulted a physician for their TIA symptoms and 35.7% of them
      had ignored their symptoms. Only 25% of those with positive history of TIA had
      been managed properly by the first contact physician. Thirteen patients (46.4% of
      those with history of TIA) had been treated with antithrombotic drugs.
      CONCLUSION: Significant numbers of patients don't worry about the symptoms of TIA
      and ignore it, another group are not subjected to full investigations to reach
      the cause and risk factors of TIA. Workshops are needed to increase education
      levels of the population about TIA and the modifiable risk factors of stroke.

PMID- 22473187
TI  - Trinucleotide repeat analysis of spinocerebellar ataxia patients in Oman.
AB  - OBJECTIVE: To explore the profile of cytosine/adenine/guanine (CAG) repeat
      expansion in Omani spinocerebellar ataxia (SCA) patients. METHODS: Ten SCA
      patients attending the Sultan Qaboos University Hospital Neurologic clinics, Al
      Khoud, Oman in the 3 years starting from January 2000 were recruited for this
      study. Genomic DNA was extracted from peripheral blood samples and CAG repeat
      expansion analysis was carried out by polymerase chain reaction and sequencing,
      when required. RESULTS: The CAG triplet repeats leading to polyglutamine
      expansion and neurodegeneration are seen in spinocerebellar ataxias 1, 2, 3, 6, 7
      and 17. By using primers for SCA 1, 2, 3 and 7, we found the repeats were in the
      normal range and triplet repeats do not seem to be a common cause for ataxia in
      Oman. CONCLUSION: Spinocerebellar ataxia in Oman has the normal range of CAG
      repeats for the commonly found SCA1, SCA2, SCA3 and SCA7.

PMID- 22473188
TI  - Do peroperative supine and prone positions have an effect on postspinal headache
      incidence?
AB  - OBJECTIVE: The study was planned to investigate the possible effects of
      peroperative prone and supine positions on postspinal headache incidence.
      METHODS: This prospective study was completed at Demet Hospital, Ankara, Turkey
      between January-July 2003.  Two groups of patients were studied, Group 1
      comprised randomly selected male American Society of Anesthesiology
      Classification grade 1 (ASA 1) patients with an age range of 20-40, who were
      scheduled for pilonidal sinus operation. Group 2 comprised randomly selected male
      ASA1 patients with an age range of 20-40 who were planned for knee arthroscopy.
      After both groups were given spinal anesthesia in the sitting position with a 22
      gauge Quincke needle, the patients who were scheduled for pilonidal sinus
      operation were laid in the prone position, while the patients planned for
      arthroscopy were laid in the supine position. The patients were then asked about
      postoperative headache complaints on the postoperative 3rd and 7th days. All
      patients were observed postoperatively for 2 days for analgesia. Both groups used
      only paracetamol 500mg orally for postoperative analgesia and oral fluid intake
      was permitted 3 hours after operation. RESULTS: The postoperative headache
      incidence of Group 2 (patients operated in supine) position was statistically
      higher than that of Group 1 (patients operated  in prone). The higher incidence
      of post spinal headache in the supine position was attributed to increased
      cerebrospinal fluid loss due to gravity and increased intra abdominal pressure
      associated with this position. CONCLUSION: Spinal anesthesia can be a safe method
      for  operation in the anal area in the prone position, and the prone position may
      prove superior to the supine position with respect to post-dural puncture
      headache development after spinal anesthesia practices.

PMID- 22473189
TI  - Schizophrenia relapse in relation to drug treatment.
AB  - OBJECTIVE: To assess and compare, prospectively, schizophrenia relapse in
      relation to neuroleptic medication in long term maintenance therapy. METHODS: All
      schizophrenic patients who met the DSM-IV criteria attending King Khalid
      University Hospital psychiatry outpatient clinic, Riyadh, Kingdom of Saudi Arabia
      in January 1994, and who fulfilled the inclusion criteria of the study, were
      assessed at baseline using the brief psychiatric rating scale (BPRS), quality of
      life scale and the extrapyramidal rating scale, and at each relapse and 6 weeks
      after treatment of the relapse and followed for 10 years after being allocated to
      one of 3 groups of neuroleptic medications depot (group A), conventional (group
      B) and atypical, clozapine (group C). A data collection form including
      sociodemographic data and other clinical indices was also completed for the
      patients. RESULTS: Seventy-six schizophrenic patients met the DSM-IV diagnostic
      criteria, but only 59 patients fulfilled the inclusion criteria of the study and
      4 patients quit the study. The mean age was 27.45 years and 63.6% were males and
      98.2% were Saudis. There was a statistical significance of the BPRS scores before
      and after relapse for groups A and C, but not for group B. The relapse rates at
      one year, 2 years, 3 years, and 5 years were in the range 13.3-34.6% for groups A
      and C but much higher at 35.7-85.7% for group B. CONCLUSION: Relapse rate in
      schizophrenia can be markedly reduced by effective maintenance neuroleptic
      treatments adhered to by the psychiatrist leaving more room for further reduction
      of relapse by implementing other measures such as lowering the expressed emotion,
      psychoeducation and rehabilitation. Further long-term large sample research is
      needed to affirm this.

PMID- 22473190
TI  - Symptoms analysis of mental illness among Saudi adults attending Primary Care.
AB  - OBJECTIVE: To determine the more common symptoms of mental illness among Saudi
      adult primary health care (PHC) patients, and to apply the factor analysis of the
      Rahim Anxiety and Depression (RAD) Scale. METHODS: This is a cross-sectional
      study of a sample of 641 patients that attended the PHC clinics in Al-Kharj city,
      from July to November 2000. Their ages ranged from 15 to 65 years. The RAD Scale
      was used as a self-administrating questionnaire to explore the common symptoms of
      mental illness. A factor analysis was performed by principle component analysis
      with varimax rotation of RAD Scale, with an eigen value of >1.5 for factor
      extraction. Only those items loading >0.4 were included. RESULTS: A total of 609
      patients with the mean age + SD of 33.7+13.4 responded, and of these men formed
      46.6%. The most common mental illness symptoms were getting angry easily (46%),
      tension (35%), sleeping badly (27%), not enjoying daily activities (15%), and
      unhappiness (14%). Physical symptoms reported were headaches (43%), joint pains
      (38%), fatigue (36%), stomach problem (33%), and dizziness (27%). All the 39
      items of the RAD Scale were included for factor analysis. Five factors (groups)
      were generated, which together accounted for 47% of the total variance. These
      factors were represented as: psychic depressive, psychic and somatic (headache
      and bodily pains) anxiety symptoms, somatization in the form of gastrointestinal
      complaints, somatization in the form of cardio-respiratory symptoms, and somatic
      anxiety symptoms. CONCLUSION: Both physical and psychological symptoms of mental
      illness are a burden on the PHC patients. Consequently, using the RAD scale is
      helpful in diagnosis. The factor analysis categorizes the items into different
      groups to save time and specify the disorder. This will be a simplified method in
      the PHC settings.

PMID- 22473191
TI  - Brain versus orbital MRI in evaluating idiopathic intracranial hypertension.
AB  - OBJECTIVE: To evaluate the usefulness of brain MRI as compared to orbital MRI in
      the assessment of idiopathic intracranial hypertension (IIH). METHODS: The study
      was carried out at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi
      Arabia between January 2002 and December 2003.   An MRI of the head and orbits
      was performed for 42 patients with the clinical diagnosis of IIH, and 15 normal
      volunteers.  All cases of secondary increased intracranial pressure were
      eliminated.  The images were evaluated for the presence of empty sella,
      parenchymal abnormalities, ventricular and sulcal size changes, optic disc
      elevation, and optic nerve sheath distention. RESULTS: The MRI of the head
      revealed empty sella in 29 patients and in one normal volunteer.  Brain MRI did
      not reveal any parenchymal, ventricular or cisternal abnormalities in either
      group.  Orbital MRI revealed optic nerve sheath distension and optic disc
      elevation in 36 patients, and were normal in all volunteers. CONCLUSION: Brain
      MRI has limited value in the evaluation of IIH.  Orbital MRI is the recommended
      imaging modality for this entity.

PMID- 22473192
TI  - Variations in sphenoid sinus anatomy with special emphasis on pneumatization and
      endoscopic anatomic distances.
AB  - OBJECTIVE: The purpose of this study was to present the morphometry and
      pneumatization of the sphenoid sinus in detail for the neurosurgeon for
      transnasal approach to the hypophyseal tumors and especially for functional
      endoscopic sinus surgery. METHODS: One hundred and eighty midsagittal magnetic
      resonance images, 48 bones and 29 hemi-sectioned cadaveric heads obtained from
      Ege University, Faculty of Medicine, Departments of Anatomy and Radiology were
      used in 2003. The sphenoid sinuses were classified into sellar, pre-sellar,
      conchal and post-sellar types according to the extent of their posterior limits.
      Different measurements based on the surgical approach and sinus size were
      performed. RESULTS: Conchal type sinus was observed in 1.9%, pre-sellar type 9%,
      sellar type 52.9% and post-sellar type 36.2% of the specimens. Conchal type
      sphenoid sinus was not observed in males, but in 1.7% of females. Pre-sellar type
      was observed in 5.6% of males and 2.8% of females. Sellar type was found in 24.4%
      of males and 23.9% females, and post-sellar type in 19.5% of males and 22.2% of
      females. The sphenoid sinus length at the upper and lower parts was 13.51+/
      3.25mm and 24.57+/-6.65mm.  The sphenoid sinus height at the anterior and
      posterior parts was 21.27+/-4.25mm and 14.5+/-4.07mm.  Distance from the ostium
      to limen was 56.6+/-5.6mm and from ostium to sill was 64.6+/-6.11mm in cadaveric
      specimens. In MR images, distance from the ostium to the sill was 68.7+/-5.9mm
      and from sella to sill 82.8+/-6.2mm. CONCLUSION: Sphenoid sinus variations
      observed in pneumatization, size, localization and shape are important in
      providing a better surgical approach and avoiding surgical complications.

PMID- 22473193
TI  - Location of the motoneurons of the mylohyoid muscle in the rat. A fluorescence
      and Nissl study.
AB  - OBJECTIVE: To locate the neuronal motor cells of the mylohyoid muscle and discuss
      their topographical organization. METHODS: The present study was conducted at the
      Department of Anatomy and Histology, Faculty of Medicine, University of Jordan,
      Amman, Jordan between 2002 and 2003. The mylohyoid muscle in 15 albino rats was
      injected with 15 mliter of a retrogradely transported fluorescent material DAPI
      Pr. After a survival period of 48 hours, animals were sacrificed, fixed in situ
      and brains harvested. The caudorostral transverse sections of the hindbrains were
      examined under the fluorescence microscope to detect the fluorescing cells, which
      were immediately photographed. Sections containing the labeled cells were
      charted, stained with 1% thionine and photographs obtained through light and
      fluorescence microscopes at different magnifications. The place and shape of all
      labeled cells were singled out by asset of their charted referring photographs of
      hindbrain sections, which display the entire motor trigeminal nucleus. RESULTS:
      The results showed that the fluorescent cell increase was found to occupy the
      rostromedial part of the ipsilateral motor trigeminal nucleus. The nucleus was
      large at its caudal third; the labeled cells are mainly those of the medial
      "subgroup".  These cells are rationally distinct and lie alongside the internal
      loop of the facial nerve. At the middle third, most of the medial "subgroup" was
      found labeled.  At its middle, the nucleus found was well developed, attained an
      appreciable size and its medial "subgroup" was somewhat distinct.  Whereas, at
      the rostral third, the nucleus was larger, the medial group was more distinct and
      all cells were labeled. The medial cellular mass of the nucleus showed reduced
      labeled cells at the rostral end. CONCLUSION: This study demonstrates that the
      rostromedial part of the motor trigeminal nucleus represents the absolute
      territorial domain of the mylohyoid muscle motoneurons.

PMID- 22473194
TI  - Cervical internal carotid artery pseudoaneurysm following stab injury.
AB  - Carotid artery pseudoaneurysm is a rare complication of injury to the head and
      neck, which has been traditionally managed by an open surgical repair to avoid
      the occurrence of devastating cerebral strokes. Their treatment presents a
      challenge because of the risk of serious neurological events. This report
      presents a case of a stab penetrating injury to the left upper neck (Monson's
      zone-III), which resulted in ipsilateral seventh and twelfth cranial nerve palsy
      and contra lateral hemiparesis, and false aneurysm of the internal carotid
      artery. After excision of the aneurysm, the internal carotid artery was ligated.
      The postoperative course was uneventful, and the patient remains free of
      symptoms.

PMID- 22473195
TI  - Postpartum cerebral vein thrombosis.
AB  - Pregnancy increases the risk of cerebrovascular accidents to approximately 13
      times the expected rate. Most of the cerebrovascular accidents are due to
      cerebral venous thrombosis. Headache, seizures and focal neurological deficits
      are some of the symptoms of cerebral venous thrombosis. Headache can also be due
      to postural puncture, pre eclampsia and eclampsia in the postpartum period. 
      Neuroimaging with MRI with contrast helps in the diagnosis of cerebral venous
      thrombosis and giving a definite diagnosis, which aids in the treatment and
      prognosis. The cases presented in this report highlight the importance of
      investigations such as MRI or CT in the diagnosis of cerebral venous thrombosis
      in pregnancy and puerperium.

PMID- 22473196
TI  - Successful outcome after evacuation of intracranial hematoma following
      thrombolysis in acute myocardial infarction.
AB  - Thrombolytic therapy is the modality of choice for the treatment of life
      threatening thrombosis in various vascular territories and nowadays, is used
      extensively in the setting of acute myocardial infarction. There is, however, the
      omnipresent danger of serious bleeding inherently associated with the use of all
      thrombolytics which if it occurs in the brain, can lead to potentially serious
      neurological impairment and even death. In our report, we describe the successful
      surgical management of a streptokinase-induced intracranial hemorrhage. Timely
      neurosurgical intervention is advocated as the optimal approach for this
      particular side effect of thrombolytic agents.

PMID- 22473197
TI  - Ascites as first presentation of ventriculo-peritoneal shunt infection in a
      neonate.
AB  - Infection is a common complication of ventriculoperitoneal shunts, and ascites is
      one of the rare manifestations of shunt infection. We report a neonate in whom
      shunt infection is presented only by ascites. The causative organism, coagulase
      negative staphylococci, was detected only in the cerebrospinal fluid although
      peritoneal fluid analysis was consistent with infection. Our patient shows the
      importance of considering shunt infection when unexplained ascites is the first
      and only manifestation in neonates with ventriculoperitoneal shunts.

PMID- 22473198
TI  - Multiple spinal ring-enhancing schwannomas.
AB  - We present a case of intradural multiple ring-enhancing lesions in a 20-year-old
      male with symptoms and signs of progressive spastic paraparesis. An MRI of the
      thoracolumbar area showed 2 peculiar ring-enhancing lesions, at the level of T12
      and L1. The differential diagnosis includes inflammatory or infectious lesions in
      addition to rare cystic tumors. The patient underwent surgical resection of the 2
      lesions with an uneventful perioperative course. Histologically, the diagnosis
      was consistent with cystic schwannomas.

PMID- 22473199
TI  - Airway management of mucopolysaccharidosis with cervical spine involvement.
AB  - Mucopolysaccharidoses are a group of inherited disorders occasionally accompanied
      by cervical spine involvement complicating tracheal intubation. In this study, we
      review and discuss 5 cases of mucopolysaccharidosis with cervical spinal
      involvement.

PMID- 22473200
TI  - Radiographic abnormalities in acute lymphoblastic leukemia.

PMID- 22473201
TI  - Comparing the effects of propranolol and ergotamine-c in prophylaxis treatment of
      migraine in Iranian patients.

PMID- 22473202
TI  - Triple-H therapy for vasospasm associated with subarachnoid hemorrhage.

PMID- 22473203
TI  - The advantage of the Gigli saw in performing mid-frontobasal craniotomy over the
      power driven tools.

PMID- 22473204
TI  - Anxiety and depression symptoms among paraplegic patients.

PMID- 22473205
TI  - Voluntary seatbelt usage. Did we reach there yet?

PMID- 22473206
TI  - Optimizing tibial P37 somatosensory evoked potentials for intraoperative
      monitoring.

PMID- 22473207
TI  - Growth and photoelectrochemical properties of ordered CuInS2 nanorod arrays.
AB  - CuInS(2) nanorod array structures are synthesized via a template-free and non
      vacuum route for the first time. The obtained CuInS(2) thin films show promising
      conversion efficiency in a two-electrode photoelectrochemical cell.

PMID- 22473209
TI  - Short nucleosome repeats impose rotational modulations on chromatin fibre
      folding.
AB  - In eukaryotic cells, DNA is organized into arrays of repeated nucleosomes where
      the shorter nucleosome repeat length (NRL) types are associated with
      transcriptionally active chromatin. Here, we tested a hypothesis that systematic
      variations in the NRL influence nucleosome array folding into higher-order
      structures. For NRLs with fixed rotational settings, we observed a negative
      correlation between NRL and chromatin folding. Rotational variations within a
      range of longer NRLs (188 bp and above) typical of repressed chromatin in
      differentiated cells did not reveal any changes in chromatin folding. In sharp
      contrast, for the shorter NRL range of 165-177 bp, we observed a strong periodic
      dependence of chromatin folding upon the changes in linker DNA lengths, with the
      172 bp repeat found in highly transcribed yeast chromatin imposing an unfolded
      state of the chromatin fibre that could be reversed by linker histone. Our
      results suggest that the NRL may direct chromatin higher-order structure into
      either a nucleosome position-dependent folding for short NRLs typical of
      transcribed genes or an architectural factor-dependent folding typical of longer
      NRLs prevailing in eukaryotic heterochromatin.

PMID- 22473208
TI  - EBV and human microRNAs co-target oncogenic and apoptotic viral and human genes
      during latency.
AB  - Epstein-Barr virus (EBV) controls gene expression to transform human B cells and
      maintain viral latency. High-throughput sequencing and crosslinking
      immunoprecipitation (HITS-CLIP) identified mRNA targets of 44 EBV and 310 human
      microRNAs (miRNAs) in Jijoye (Latency III) EBV-transformed B cells. While 25% of
      total cellular miRNAs are viral, only three viral mRNAs, all latent transcripts,
      are targeted. Thus, miRNAs do not control the latent/lytic switch by targeting
      EBV lytic genes. Unexpectedly, 90% of the 1664 human 3'-untranslated regions
      targeted by the 12 most abundant EBV miRNAs are also targeted by human miRNAs via
      distinct binding sites. Half of these are targets of the oncogenic miR-17~92
      miRNA cluster and associated families, including mRNAs that regulate
      transcription, apoptosis, Wnt signalling, and the cell cycle. Reporter assays
      confirmed the functionality of several EBV and miR-17 family miRNA-binding sites
      in EBV latent membrane protein 1 (LMP1), EBV BHRF1, and host CAPRIN2 mRNAs. Our
      extensive list of EBV and human miRNA targets implicates miRNAs in the control of
      EBV latency and illuminates viral miRNA function in general.

PMID- 22473210
TI  - Tightening of the ATP-binding sites induces the opening of P2X receptor channels.
AB  - The opening of ligand-gated ion channels in response to agonist binding is a
      fundamental process in biology. In ATP-gated P2X receptors, little is known about
      the molecular events that couple ATP binding to channel opening. In this paper,
      we identify structural changes of the ATP site accompanying the P2X2 receptor
      activation by engineering extracellular zinc bridges at putative mobile regions
      as revealed by normal mode analysis. We provide evidence that tightening of the
      ATP sites shaped like open 'jaws' induces opening of the P2X ion channel. We show
      that ATP binding favours jaw tightening, whereas binding of a competitive
      antagonist prevents gating induced by this movement. Our data reveal the inherent
      dynamic of the binding jaw, and provide new structural insights into the
      mechanism of P2X receptor activation.

PMID- 22473212
TI  - Caesarean delivery vasopressor management.
AB  - PURPOSE OF REVIEW: This review assesses the maternal and fetal effects of
      vasopressor administration during spinal anaesthesia for caesarean delivery, with
      emphasis on recent findings. RECENT FINDINGS: Maternal heart rate is a good
      surrogate for cardiac output. The initial hypotensive effect of spinal
      anaesthesia is caused by a rapid decrease in systemic vascular resistance, which
      makes alpha-agonists the logical first-line therapy. Effective prophylactic
      phenylephrine administration can be associated with reduced maternal cardiac
      output, but this has not been associated with adverse maternal or fetal effects.
      Prophylactic phenylephrine infusion can cause hypertension if increasing arterial
      pressure does not trigger a timely reduction in the rate of administration.
      Phenylephrine has been used safely in mothers with cardiac disease and in
      pregnancies with suspected fetal compromise. Fetal genotype may increase
      resistance to ephedrine-induced acidosis. The combination of vagolytics and
      vasopressors has caused maternal hypertensive crises with serious adverse
      outcome. SUMMARY: Phenylephrine is the current vasopressor of choice for the
      prevention of maternal hypotension and nausea. Phenylephrine regimens need to be
      developed that can reliably and safely be used with noninvasive blood pressure
      cycle times less frequent than every minute. Further vasopressor should be used
      with caution when vagolytic therapy is, quite rightly, used to treat bradycardia
      associated with hypotension.

PMID- 22473213
TI  - Epidural analgesia and maternal fever:  a clinical and research update.
AB  - PURPOSE OF REVIEW: Maternal fever following epidural analgesia complicates up to
      one-third of nulliparous labors. Although generally benign, maternal fever is
      associated with both excess healthcare costs and an increased risk of adverse
      maternal and neonatal outcomes; therefore, this topic is of interest to
      anesthesiologists, obstetricians and pediatricians alike. The purpose of this
      review is to examine the latest research on the topic of epidural-related
      maternal fever, with special focus on the clinical relevance of new information.
      RECENT FINDINGS: Research over the past 18 months has increased our understanding
      of the cause of epidural-related fever and brought additional supportive evidence
      that proactive labor management may decrease risk. Additionally, there were
      innovative investigations of potential pharmacologic interventions to reduce
      maternal, and potentially fetal, risk. SUMMARY: Significant research advances
      were made in the last 18 months around the topic of epidural-related fever, but
      major gaps in knowledge persist especially with understanding the precise
      mechanism. The most pressing area of research is the development of well
      tolerated and effective prophylactic interventions to prevent maternal and fetal
      exposure to hyperthermia and inflammation.

PMID- 22473211
TI  - FtsA forms actin-like protofilaments.
AB  - FtsA is an early component of the Z-ring, the structure that divides most
      bacteria, formed by tubulin-like FtsZ. FtsA belongs to the actin family of
      proteins, showing an unusual subdomain architecture. Here we reconstitute the
      tethering of FtsZ to the membrane via FtsA's C-terminal amphipathic helix in
      vitro using Thermotoga maritima proteins. A crystal structure of the FtsA:FtsZ
      interaction reveals 16 amino acids of the FtsZ tail bound to subdomain 2B of
      FtsA. The same structure and a second crystal form of FtsA reveal that FtsA forms
      actin-like protofilaments with a repeat of 48 A. The identical repeat is observed
      when FtsA is polymerized using a lipid monolayer surface and FtsAs from three
      organisms form polymers in cells when overexpressed, as observed by electron
      cryotomography. Mutants that disrupt polymerization also show an elongated cell
      division phenotype in a temperature-sensitive FtsA background, demonstrating the
      importance of filament formation for FtsA's function in the Z-ring.

PMID- 22473214
TI  - Recent trends in simulation for obstetric anesthesia.
AB  - PURPOSE OF REVIEW: The use of simulation in medicine has grown significantly over
      the past 2 decades. Simulation in obstetric anesthesia can be divided into four
      broad uses: technical skills, nontechnical or teamwork skills, individual
      clinical competence, and the safety of the clinical environment. This review will
      describe recent trends in the use of simulation in several of these categories.
      RECENT FINDINGS: Simulation continues to be an important part of skills
      (technical and cognitive) and teamwork training in obstetric anesthesia. The
      acquisition of simple and complex technical skills appears to be improved with
      the use of simulation. However, the assessment of these skills is currently done
      in the simulated environment. Simulation is also important in assessing and
      enhancing the safety of a labor unit. Two simulation trends have recently
      evolved. Instructional articles describing how to best perform simulation have
      begun to appear. In addition, several review articles have been published that
      demonstrate the maturation of the body of research in this field. SUMMARY: As the
      use of simulation continues to grow, research should concentrate on whether
      anesthesia or teamwork skills learned in the simulated environment change
      behavior and improve outcomes in the clinical setting. More instructional
      publications would also facilitate the growth into more clinical environments.

PMID- 22473215
TI  - The role of recombinant activated factor VII in obstetric hemorrhage.
AB  - PURPOSE OF REVIEW: To review the literature regarding the use of recombinant
      activated factor FVII (rFVIIa) in the treatment of postpartum hemorrhage (PPH).
      RECENT FINDINGS: The previous and recent case reports and case series suggest a
      potential benefit of rFVIIa in the management of severe PPH refractory to
      standard treatment. However, the lack of randomized controlled studies limits the
      value of the available data. rFVIIa cannot work optimally if there is a shortage
      of the basic components of the coagulation cascade such as fibrinogen. New
      experimental data suggest that rFVIIa can relocate into the extravascular space
      and remain functionally active which may prolong its hemostatic effect longer
      than the short circulatory half-life indicates. SUMMARY: Although some
      preliminary guidelines have been published, the case reports and case series
      illustrate that the practice of using rFVIIa in PPH is far from uniform. rFVIIa
      should usually not be used to compensate for an inadequate transfusion therapy.
      Therefore, early and effective administration of red blood cells, fresh frozen
      plasma, fibrinogen concentrate (or cryoprecipitate), and platelets as well as the
      control of uterine atony are essential before considering administration of
      rFVIIa in the treatment of PPH.

PMID- 22473216
TI  - Effective enhancement of the performance of black dye based dye-sensitized solar
      cells by metal oxide surface modification of the TiO2 photoelectrode.
AB  - Effective enhancement of the performance of black dye based dye-sensitized solar
      cells has been achieved by MgO or Al(2)O(3) surface modification of the TiO(2)
      photoelectrode. The conversion efficiency was improved from 10.4% to 10.8% due to
      the blocking effect of the thin overlayer at the TiO(2) surface.

PMID- 22473217
TI  - The effect of preventive consultations on young adults with psychosocial
      problems: a randomized trial.
AB  - Patients with many problems often face difficulties in modifying their behavior
      as desired. Uncovered basic needs may be an important barrier. This research
      tests the effect of patient-centered consultations for 20- to 44-year-old
      patients with multiple psychosocial and lifestyle problems. We focus on resources
      and barriers for obtaining self-chosen goals within life circumstances and
      lifestyle. At 28 general practitioners, 2056 patients aged 20-44 years were
      screened with a 33-item problem-score on resources, network, lifestyle and social
      conditions. The 30% who had most problems were invited to complete a more
      comprehensive questionnaire at home. Intervention was preventive consultation
      with a 3-month follow-up. A total of 495 patients were randomized. One-year
      questionnaire follow-up showed significant improvement in Short Form Health
      related Quality of Life Mental (MCS-SF12) in the intervention group (7.3)
      compared with the control group (3.0); the difference was 4.3 (95% confidence
      interval 1.6-7.0, P = 0.002). The number of problems was reduced significantly
      more in the intervention than in the control group (1.8 versus 0.8, P = 0.03).
      Preventive consultation focusing on resources and barriers to self-chosen goals
      may improve MCS-SF12 and decrease the number of problems in patients with many
      psychosocial and lifestyle problems. This may be an indicator of improved
      specific self-efficacy and a key to lifestyle changes.

PMID- 22473218
TI  - Tea tree oil as a novel antipsoriasis weapon.
AB  - Psoriasis is a clinical skin disease that is characterized by erythematous
      scaling plaques and involves the extensor site of the extremities, the scalp and
      other surfaces of the skin. Tea tree oil (TTO) is considered an essential oil,
      obtained by steam distillation of the leaves and terminal branchlets of Melaleuca
      alternifolia. Notably,terpinen-4-ol, the major TTO constituent, has been found to
      have potent anti-inflammatory properties. It is suggested that terpinen-4-ol may
      be a novel potential agent against psoriasis. This article draws attention to the
      antipsoriatic effect of TTO and provides a theoretical molecular approach.

PMID- 22473219
TI  - The value of the CHA2DS2-VASc score for refining stroke risk stratification in
      patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort
      study.
AB  - North American and European guidelines on atrial fibrillation (AF) are
      conflicting regarding the classification of patients at low/intermediate risk of
      stroke. We aimed to investigate if the CHA2DS2-VASc score improved risk
      stratification of AF patients with a CHADS2 score of 0-1. Using individual-level
      linkage of nationwide Danish registries 1997-2008, we identified patients
      discharged with AF having a CHADS2 score of 0-1 and not treated with vitamin K
      antagonist or heparin. In patients with a CHADS2 score of 0, 1, and 0-1, rates of
      stroke/ thromboembolism were determined according to CHA2DS2-VASc score, and the
      risk associated with increasing CHA2DS2-VASc score was estimated in Cox
      regression models adjusted for year of inclusion and antiplatelet therapy. The
      value of adding the extra CHA2DS2-VASc risk factors to the CHADS2 score was
      evaluated by c-statistics, Net Reclassification Improvement (NRI) and Integrated
      Discrimination Improvement (IDI). We included 47,576 patients with a CHADS2 score
      of 0-1, from these 7,536 (15.8%) were CHA2DS2-VASc score=0, 10,062 (21.2%) were
      CHA2DS2-VASc score=1, 14,310 (30.1%) were CHA2DS2-VASc score=2, 14,188 (29.8%)
      were CHA2DS2-VASc score=3, and 1,480 (3.1%) were CHA2DS2-VASc score=4. Of the
      cohort with a CHADS2 score of 0-1, the stroke/thromboembolism rate per 100 person
      years increased with increasing CHA2DS2-VASc score (95% confidence interval):
      0.84 (0.65-1.08), 1.79 (1.53-2.09), 3.67 (3.34-4.03), 5.75 (5.33-6.21), and 8.18
      (6.68-10.02) at one year follow-up with CHA2DS2-VASc scores of 0, 1, 2, 3, and 4,
      respectively. Patients with a CHADS2 score=0 were not all 'low risk', with one
      year event rates ranging from 0.84 (CHA2DS2-VASc score=0) to 3.2 (CHA2DS2-VASc
      score=3). Results from Cox regression analyses, NRI, and IDI confirmed the
      improved predictive ability of the CHA2DS2-VASc score in the AF patients who have
      a CHADS2 score of 0-1. In conclusion, the CHA2DS2-VASc provides critical
      information on risk of stroke in AF patients with a CHADS2 score of 0-1 that can
      aid a decision of using anticoagulation. Even in patients categorised as 'low
      risk' using a CHADS2 score=0, the CHA2DS2-VASc score significantly improved the
      predictive value of the CHADS2 score alone and a CHA2DS2-VASc score=0 could
      clearly identify 'truly low risk' subjects. Use of the CHA2DS2-VASc score would
      significantly improve classification of AF patients at low and intermediate risk
      of stroke, compared to the commonly used CHADS2 score.

PMID- 22473220
TI  - 5/6 nephrectomy as a validated rat model mimicking human warfarin-related
      nephropathy.
AB  - BACKGROUND/AIMS: We previously reported that patients with chronic kidney disease
      (CKD) receiving warfarin therapy and whose international normalized ratio
      increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular
      hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this
      condition warfarin-related nephropathy (WRN). We also previously reported that
      acute excessive anticoagulation with brodifacoum (superwarfarin) induces AKI in
      5/6 nephrectomy (5/6NE) rats. Limitations of the brodifacoum model precluded a
      careful assessment of dose-response relationships. METHODS: Warfarin treatment
      was used in 5/6NE. RESULTS: Herein we report that warfarin treatment of 5/6NE
      rats resulted in a dose-dependent increase in serum creatinine (SC). The increase
      in SC following warfarin treatment was greater at 3 and 19 weeks after the
      ablative surgery, than that observed 8 weeks after the ablative surgery. The SC
      increase was correlated with the prothrombin time increase. Morphologically,
      5/6NE, but not control rats, had acute tubular injury with RBC and RBC casts in
      the tubules. Treatment with vitamin K prevented SC increase and morphologic
      changes in the kidney associated with warfarin treatment. A single episode of WRN
      did not affect the progression of CKD in 5/6NE. CONCLUSION: (1) The 5/6NE model
      of CKD is an appropriate animal model to study the pathogenesis of WRN. (2) The
      pharmacokinetics of warfarin is better suited to the study of WRN than that of
      brodifacoum. (3) The more advanced stages of 5/6NE are more susceptible to WRN
      than the earlier stages. (4) Vitamin K treatment prevents WRN.

PMID- 22473222
TI  - Synthesis of 4H-cyclopenta[c]furans via cooperative PdCl2-FeCl2 catalyzed cascade
      cyclization reaction involving a novel acyl rearrangement process.
AB  - We have discovered a novel PdCl(2)-FeCl(2) catalyzed cascade cyclization
      reaction, which involves a novel acyl rearrangement process. This reaction
      affords a diverse set of poly-substituted 4H-cyclopenta[c]furan products. The
      reaction scope of this cascade process is quite broad and various internal
      acetylenes can be employed.

PMID- 22473221
TI  - The influence of health care policies and health care system distrust on
      willingness to undergo genetic testing.
AB  - PURPOSE: As the potential role of genetic testing in disease prevention and
      management grows, so does concern about differences in uptake of genetic testing
      across social and racial groups. Characteristics of how genetic tests are
      delivered may influence willingness to undergo testing and, if they affect
      population subgroups differently, alter disparities in testing. METHODS: Conjoint
      analysis study of the effect of 3 characteristics of genetic test delivery (ie,
      attributes) on willingness to undergo genetic testing for cancer risk. Data were
      collected using a random digit dialing survey of 128 African American and 209
      white individuals living in the United States. Measures included conjoint
      scenarios, the Revised Health Care System Distrust Scale (including the values
      and competence subscales), health insurance coverage, and sociodemographic
      characteristics. The 3 attributes studied were disclosure of test results to the
      health insurer, provision of the test by a specialist or primary care doctor, and
      race-specific or race-neutral marketing. RESULTS: In adjusted analyses,
      disclosure of test results to insurers, having to get the test from a specialist,
      and race-specific marketing were all inversely associated with willingness to
      undergo the genetic test, with the greatest effect for the disclosure attribute.
      Racial differences in willingness to undergo testing were not statistically
      significant (P=0.07) and the effect of the attributes on willingness to undergo
      testing did not vary by patient race. However, the decrease in willingness to
      undergo testing with insurance disclosure was greater among individuals with high
      values distrust (P=0.03), and the decrease in willingness to undergo testing from
      specialist access was smaller among individuals with high competence distrust
      (P=0.03). CONCLUSIONS: Several potentially modifiable characteristics of how
      genetic tests are delivered are associated with willingness to undergo testing.
      The effect of 2 of these characteristics vary according to the level of health
      care system distrust, suggesting that policy decisions about delivery of genetic
      testing may influence differences in uptake across patient subgroups defined by
      levels of distrust rather than by race.

PMID- 22473223
TI  - Biomimetic approach to forming chitin/aragonite composites.
AB  - Biomimetic materials which display the complexity of biominerals like nacre are
      synthetically difficult to prepare. The formation of chitin/calcium carbonate
      composites, where CaCO(3) is present as aragonite, was achieved via reacetylation
      of preformed chitosan scaffolds followed by the combination of presoaking of
      chitin templates with mineral solutions in the presence of poly(acrylic acid).
      The as-synthesised composites are comprised of well-ordered ribbons of aragonite
      crystals held within an organic matrix, mimicking the structure of nacre.

PMID- 22473224
TI  - Long-acting injectable antipsychotics. Review and recent developments.
AB  - Long-acting injectable antipsychotics, also known as 'depots', were developed in
      the late 1960s as an attempt to improve compliance and long-term management of
      schizophrenia.  Despite their availability for over 30 years, guidelines for
      their use and data on patients for whom long-acting injectable antipsychotics are
      most indicated are sparse and vary considerably. A review of the perceived
      advantages and disadvantages of using long-acting injectable antipsychotics is
      provided in this article, as well as a review of the literature to update
      clinicians on the current advances of this therapeutic option to optimize
      compliance and long-term management of chronic schizophrenia.

PMID- 22473225
TI  - Relation between cranial venous return and hand preference by magnetic resonance
      angiography.
AB  - OBJECTIVE: This study was conducted to determine whether there is a relationship
      between hand preference and the site of cranial venous return. Magnetic resonance
      angiography was used for the determination of the site of dominance of cranial
      venous return. METHODS: Forty-seven right-handed and 45 left-handed subjects
      participated in the study conducted at the Sevgi Hospital in Ankara, Turkey
      between 1996 and 2000. The site of cranial venous return was determined by
      calibration of the superior jugular bulbus and named as right (R), left (L) and
      right-left (R-L). Calibrations of superior jugular bulbus were analyzed by one
      way variance analyses. RESULTS: There were statistically significant differences
      when analyzing the hand preference and calibration in the subjects with a venous
      return from the left, than from the right and right-left. The site of venous
      return (R, L, R-L) and venous calibration were analyzed by student t-test and
      were not statistically significant. CONCLUSION: The venous return was from the
      left in right-handed subjects and from the right in left-handed subjects.
      Correlation's of hand preference and age and sex could not be made. For both
      sided venous return, ambidexterity could not be determined.

PMID- 22473226
TI  - Effect of combined spa and physical therapy on pain in various chronic diseases.
AB  - OBJECTIVE: The purpose of this study was to exhibit the effect of combined
      therapy (spa and physical therapy) on pain in various chronic diseases. METHODS:
      Retrospectively, 472 (58.1% female and 41.9% male) spa and physical therapy
      patients with a mean age of 53.4 +/- 12.5 years were evaluated during 2001-2004
      from the archives of Dumlupinar University TUTAV Thermal Cure Center. Before,
      after therapy and before discharging, visual analog scale (VAS) for pain, heart
      and respiratory rates, systolic and diastolic blood pressures were measured for
      hemodynamic evaluations. RESULTS: Arthrosis (230 patient, 48.7%) was found to be
      the main problem in our patients. Ankle arthrosis, fibromyalgia and cervical disc
      herniation were found with the highest VAS values compared to other pathologies
      before spa therapy (p<0.05).  Immediately after spa therapy and before discharge,
      VAS values were lower than before treatment (p<0.05). Immediately after spa
      therapy, the highest decreases in VAS values were observed in coxarthrosis and
      gonarthrosis patients (p<0.05). Coxarthrosis and nonarticular patients had the
      lowest VAS values before discharge than other pathologies (p<0.05). No
      statistical differences were found between male and female VAS values in all
      stages of treatment (p>0.05). Heart and respiratory rate were statistically
      increased (p<0.01), diastolic blood pressure was decreased (p<0.01) but not
      changed in systolic blood pressure (p>0.05) immediately after spa therapy. Before
      discharging, all hemodynamic parameters were found statistically decreased before
      treatment and immediately after spa therapy (p<0.01). CONCLUSION: A combination
      of spa and physical therapy decreases pain and improves functional capacity
      without any hemodynamic risk in rheumatological, neurological and cardiac
      patients.

PMID- 22473227
TI  - Ulnar neuropathy at Jordan University Hospital.
AB  - OBJECTIVE: To study the causes, clinical and electromyography/nerve conduction
      study (EMG/NCS) findings and treatment modalities in Jordanian patients with
      ulnar neuropathy (UN) observed in a tertiary care referral center and compare the
      findings with those from Western literature. METHODS: The case notes of 20
      patients with UN referred to the neurophysiology department at Jordan University
      Hospital, Amman, Jordan, between January 2002 and January 2004 were reviewed. The
      clinical presentation, causes, EMG/NCS and treatment modalities were registered.
      RESULTS: Among the 20 patients, 18 were male and 2 female with a mean age of 39
      years (range 14-68 years). Ten cases were traumatic UN while the other 10 were
      presumably idiopathic cubital tunnel syndrome (CTS). The most common clinical
      manifestations were paresthesiae of 4th/5th digits and weakness/atrophy of small
      hand muscles. All 10 cases of traumatic UN were axonal on EMG/NCS while among the
      other 10 with CTS, 3 diabetics had axonal injury and 6 out of 7 nondiabetics had
      a demyelinating injury, 3 sensorimotor and 3 pure sensory. Additional carpal
      tunnel syndrome was found in 5 patients. Needle EMG was abnormal only in cases of
      abnormal ulnar sensory action potential. Nine out of 10 with traumatic UN had
      surgery while only 3 out of 10 with CTS had cubital tunnel release. CONCLUSION:
      Compared to previous studies from Western literature, our study shows a similar
      male predominance as well as comparable clinical and neurophysiological  findings
      and treatment modalities.

PMID- 22473228
TI  - Pediatric neuro-developmental and behavioral disorders. Practitioners'
      perspectives.
AB  - OBJECTIVE: Developmental and behavioral (DB) disorders are commonly encountered
      in the general pediatric and neurology practices. There is a strong demand for
      trained developmental pediatricians and child psychiatrists in our region. In
      this study, we aimed to study practitioner's experiences in dealing with these
      disorders and their referral practices. METHODS: Attendees of an international
      pediatric symposium on neuro-developmental and behavioral disorders were
      included. The symposium was conducted by the Department of Neurosciences, King
      Faisal  Specialist Hospital and Research Center in Jeddah from 4-6th March, 2003.
      A structured 25-item questionnaire was designed to examine their demographics,
      training, practice and referral patterns. RESULTS: A total of 167 attendees
      registered for the symposium and 131 (78%) questionnaires were returned.
      Participant's ages were 23-69 years (mean 36, SD 8.5), with 67% being females.
      Many participants were practicing general pediatrics (43.5%) and the majority
      (92%) frequently saw and followed children with DB disorders. However, only 24%
      felt highly confident in their management. As well, only 35% and 31% of
      physicians received structured developmental and psychiatry rotations, during
      their training. Those who received a structured developmental rotation felt more
      comfortable in making the correct diagnosis (odds ratio (OR) 4, 95% confidence
      interval (CI) 1.2-14, p=0.01) and in providing appropriate treatment (OR 3.8, 95%
      CI 1.4-11, p=0.006). Many participants (32%) had no direct access to a
      developmental pediatrician or child psychiatrist for referrals. CONCLUSION:
      Developmental and behavioral disorders are common in daily pediatric practice.
      Most practitioners did not receive a structured rotation covering these disorders
      during their training and were not highly confident in managing affected
      children. Given the limited number of developmental pediatricians and child
      psychiatrists, we highly recommend appropriate developmental and psychiatric
      training for practitioners.

PMID- 22473229
TI  - Pro-inflammatory cytokines in autistic children in central Saudi Arabia.
AB  - OBJECTIVE: Abnormal inflammatory immune response might contribute to autism. Pro
      inflammatory cytokines could induce some of the symptoms and signs of autism.
      Such as, social withdrawal eating and sleep disturbance. The aim of the current
      study was to examine whether autism spectrum disorders in Riyadh area are
      accompanied by activation of the pro-inflammatory response system. METHODS: The
      study was conducted in the Riyadh area between September 2003 and April 2004.
      Seventy-seven autistic child from the Riyadh area participated in the study, with
      confirmed diagnosis according to E-2 diagnostic criteria for autistic spectrum
      disorders. The parents/guardians filled a simple related questionnaire, then
      serum concentrations of tumor necrosis factor-a (TNF-a), interleukin-1 (IL-1) and
      interleukin-6 (IL-6) were measured in 65 autistic, 8 attention deficit disorder,
      2 children with Rett's syndrome and 2 children with Asperger syndrome. The
      results were compared to age, and sex matched control children. RESULTS: This
      study showed a significantly increased production of TNF-a, IL-1 and IL-6 from
      the sera of autistic, attention deficit disorder, Rett's syndrome and Asperger
      syndrome children. There was no correlation between TNF-a, IL-1 or IL-6 and the
      degree of autism or the age of the affected child. Significant higher incidence
      of social withdrawal, sleeping and eating disorders were found among autism
      spectrum disorders compared to control. CONCLUSION: These results suggest that
      autism may be accompanied by an activation of the macrophages. It is hypothesized
      that increased production of pro-inflammatory cytokines could play a role in the
      pathophysiology of autism spectrum disorders, such as social withdrawal, eating
      and sleeping disorders.

PMID- 22473230
TI  - Sleep habits and patterns among medical students.
AB  - OBJECTIVE: This study was designed to assess sleep patterns among male medical
      students at different academic levels. METHODS: Participants in this study were
      healthy male medical students in the first (L1), second (L2) and third (L3)
      academic levels of the College of Medicine, King Saud University, Riyadh, Saudi
      Arabia.  The study was conducted during November 2001.  A self-administered
      questionnaire was distributed to students to assess age, academic level,
      registered credit hours, sleep-wake schedule, naps, quality of sleep, total sleep
      time at night, possible factors affecting bedtime, and daytime sleepiness using
      the Epworth Sleepiness Scale (ESS). RESULTS: The final analysis included 129
      students.  Total sleep time at night + nap of the whole group was 5.9 +/- 1.6
      hours.  Twenty-nine students (22.4%) were defined to have excessive daytime
      sleepiness (EDS) based on ESS score of >10. Also, 83.3% of students reported
      napping during the daytime more than twice per week. CONCLUSION: Analysis of the
      sleep pattern of male medical students revealed that this group is sleep
      deprived, which in turn may affect their academic performance.

PMID- 22473231
TI  - Vaginismus treatment. Hypnotherapy versus behavior therapy.
AB  - OBJECTIVE: To investigate the effectiveness of hypnotherapy in the treatment of
      vaginismus compared to behavior therapy. METHODS: A consecutive sample of 36
      women with vaginismus (DSM-IV criteria) referred to the out-patient psychiatry
      clinic at King Abdul-Aziz University Hospital in Riyadh between 1999-2003 were
      divided into 2 groups for either treatment on a random basis. A female
      psychologist independently and carefully assessed patients before and after
      treatment. Patients were treated until they achieved satisfactory sexual
      intercourse. RESULTS: Although both behavior therapy and hypnotherapy were
      successful in treating vaginismus, hypnotherapy performed better than behavior
      therapy in reducing the level of the wife's sex-related anxiety and in improving
      the husband's sexual satisfaction score. Success tended to occur faster in women
      treated with hypnotherapy as they received fewer treatment sessions. Women with
      vaginismus can be successfully treated by hypnotherapy without simultaneous
      treatment of their husbands. CONCLUSION: Hypnotherapy can provide an acceptable
      time and cost effective therapeutic tool that helps resolve vaginismus and
      improves sexual satisfaction in both spouses.

PMID- 22473232
TI  - Brachial plexus injury in vaginal delivery.
AB  - OBJECTIVE: To study the incidence and persistence of brachial plexus injury (BPI)
      and the ability to predict its occurrence pre-natally depending on patients'
      criteria and antepartum-partum course. METHODS: During a 3-year period from June
      2001-June 2004 at Queen Alia Military Hospital, Royal Medical Services, Amman,
      Jordan, all newborns with BPI were identified (patients group) and followed-up
      for a one-year period. Obstetric details were compared with a control group who
      were delivered during the same period. Obstetrical neonatal features of both
      groups were compared. RESULTS: Over the mentioned period, 30 cases of BPI were
      identified from a total 11560 deliveries (0.25%). Persistency for more than one
      year was present in 5 cases (17%). Both groups were compared regarding certain
      known maternal and intra-partum risk factors. Significant risk was history of
      having shoulder dystocia in previous and current pregnancy (p<0.05) and duration
      of labor (p<0.05). CONCLUSION: Brachial plexus impairment was encountered in the
      presence of normal course of labor and delivery. No predictable risk factors were
      found that could be avoided antenatally to prevent BPI.

PMID- 22473233
TI  - Bilateral sternalis muscles.
AB  - Bilateral sternalis muscles were observed during dissection of the thoraco
      abdominal region of a male cadaver. A full description of the muscles, as well as
      their attachments and innervations were reported. A brief review of the existing
      literature, regarding the nomenclature, incidence, attachments, innervations and
      clinical relevance of the sternalis muscle, is also presented.

PMID- 22473234
TI  - Osteomalacic myopathy due to celiac disease.
AB  - Celiac disease is a gluten-sensitive enteropathy characterized by malabsorption
      resulting from inflammatory injury to the mucosa of the small intestine.  It is
      well known to be associated with a variety of neurological disorders including
      epilepsy, myopathy, neuropathy and ataxia.  The nature of this association is
      unclear. Although osteomalacia secondary to vitamin D deficiency is a recognized
      complication of celiac disease, however, severe osteomalacic myopathy as the only
      presentation of celiac disease is extremely rare.  We present 2 interesting cases
      of osteomalacic myopathy secondary to celiac disease, which were treated
      successfully with full recovery.  An important and unique observation was the
      brisk reflexes noticed in both patients.  The mechanism behind this phenomenon is
      not well understood.  Work-up for celiac disease is warranted in any young
      patient that presents with myopathy.

PMID- 22473235
TI  - Large deep venous anomaly presenting as a left frontal lesion.
AB  - Venous angiomas' also known as deep vein anomalies (DVA), are one of the well
      described brain vascular malformations. Frequently they are diagnosed as an
      incidental finding on neuroimaging (CT or MRI). A DVA may present as a single
      enhancing venous channel or as a large vascular abnormality illustrated on
      cerebral angiogram. Such a large DVA may mimic other intracranial lesions that
      mandate surgical intervention. We describe the radiological findings on CT, MRI,
      MRA and cerebral angiography of a 26-year-old male who presented with a few
      months' history of recurrent attacks of light-headiness, dizziness and slurring
      of speech that usually lasted for 2 minutes and resolved spontaneously. Cerebral
      angiography illustrated enlarged medullary veins draining into a central venous
      trunk then into the superior sagittal sinus resembling a caput medusa sign. Large
      DVAs may present radiologically as a brain lesion. Early recognition of these
      anomalies would avoid unnecessary or harmful intervention of this, otherwise,
      benign pathology.

PMID- 22473236
TI  - Alveolar hydatid disease of the spine causing paraplegia.
AB  - Hydatid disease involving the vertebral body and paravertebral soft tissues is a
      rare disease with poor prognosis. We report a case of spinal cord compression
      caused by secondary extradural cysts.

PMID- 22473237
TI  - Neurocysticercosis in pregnancy.
AB  - Neurocysticercosis is a common cause of adult onset epilepsy. Neurocysticercosis
      in pregnancy can present with convulsions and may be difficult to differentiate
      from a pregnancy related disorder. We present a case of neurocysticercosis
      diagnosed by magnetic resonance imaging.

PMID- 22473238
TI  - Prevalence of minor psychiatric illnesses among attendants of a Primary Health
      Care Center in Northwestern Saudi Arabia.

PMID- 22473239
TI  - Bell's palsy complicating pregnancy.

PMID- 22473241
TI  - Crossed cerebro-cerebellar diaschisis.

PMID- 22473242
TI  - Crossed cerebellar diaschisis after status epilepticus in a young child.
AB  - We report on a 3.8-year-old girl who was born preterm. Due to a posthemorrhagic
      hydrocephalus she had a ventriculoperitoneal shunt. Magnetic resonance imaging
      (MRI) showed mild atrophy of the left cerebellum. She was found unresponsive in a
      febrile state. After the application of midazolam she regained consciousness.
      There were no epileptic discharges on electroencephalogram. MRI with diffusion
      weighted sequences showed areas of hyperintensity in the right cerebrum. After
      the patient deteriorated again, MRI showed signs of increased intracranial
      pressure and high signal intensity throughout the right cerebral and left
      cerebellar hemispheres, suggesting crossed cerebellar diaschisis (CCD) most
      likely resulting from a nonconvulsive status epilepticus (SE). A follow-up MRI
      showed progressive brain atrophy. CCD after SE might be caused by cortical
      excitatory input through the cortico-pontine-cerebellar pathway. Alternatively,
      the cerebral edema in SE may decrease neuronal cell activity in the contralateral
      cerebellar hemisphere. The unilateral cerebellar atrophy before the onset of CCD
      might be attributed to impaired neuronal connections after peripartal cerebral
      injury. This case presents a young child with a combination of two CCDs, at first
      due to perinatal brain injury, and at second to SE. MRI with diffusion-weighted
      sequences can detect CCD at an early stage.

PMID- 22473243
TI  - Unrecognized citrullinemia mimicking encephalitis in a 14-year-old boy:
      unexpected result through the use of a standardized lumbar puncture protocol.
AB  - Citrullinemia is a urea cycle disorder caused by deficiency of argininosuccinate
      synthetase. Late onset forms can remain undiscovered until a decompensation that
      can resemble encephalitis. Herein, we report a 14-year old patient with suspected
      encephalitis with fluctuating episodes of confusion. EEG mainly showed bilateral
      slowing with some spikes plus spike waves; and was interpreted as suspicious for
      encephalitis. Brain MRI was normal. Leukocytes in CSF were slightly elevated.
      Treatment for a CNS infectious disease was begun. Symptoms did not resolve and
      there were several episodes of confusion, so a repeat lumbar puncture was
      performed according to a standardized protocol including an amino acid profile.
      An elevation of citrulline in CSF was found, which ultimately led to the
      diagnosis of a late onset citrullinemia. The establishment of this diagnosis will
      protect the patient from the sequelae of unrecognized and thus untreated episodes
      of hyperammonemia. Thus, following a standardized lumbar puncture protocol can be
      essential to detect patients with otherwise unrecognized underlying metabolic
      disorders that are not suspected because of clinical symptoms. In addition, it is
      important to stress that an ammonia concentration should be determined in any
      patient with neurological signs like confusion.

PMID- 22473244
TI  - Acute disseminated encephalomyelitis in children: a single institution experience
      of 28 patients.
AB  - The aim of this study is to describe the clinical, laboratory, and neuroimaging
      features, treatment and outcome of acute disseminated encephalomyelitis (ADEM) in
      Taiwanese children to compare with two series from United States of America and
      Japan. We retrospectively reviewed the medical records and magnetic resonance
      images of 28 children, 23 boys and 5 girls, with ADEM between January 2001 and
      December 2009. Their mean age at disease onset was 6 years 9 months. Twenty four
      children experienced a prodromal illness. There was no special seasonal
      distribution in our patients. They presented mostly with impaired consciousness
      and headache. Cerebrospinal fluid samples of 21 patients were analyzed and none
      showed intrathecal oligoclonal bands. Magnetic resonance imaging showed variable
      findings: lesions with abnormal signal changes frequently found in the
      subcortical white matter of frontal and parietal lobes. No patient showed
      cortical gray matter involvement. We also found a high rate of deep gray matter
      involvement including thalami and basal ganglia. Treating with steroids was
      usually associated with a rapid recovery and both intravenous high dose
      methylprednisolone and dexamethasone had the same effect. All patients survived.
      Twenty three patients recovered completely with only mild sequelae in the
      remaining five children.

PMID- 22473245
TI  - Turnover of registered nurses in Israel: characteristics and predictors.
AB  - BACKGROUND: In an era of global and local nursing shortages, nursing turnover has
      negative consequences in terms of diminished quality of care, increased costs and
      economic losses and decreased job satisfaction. OBJECTIVE: To examine the
      turnover rate of registered nurses in Israel by assessing the varying degree of
      turnover between economic sectors, between hospital and community facilities,
      and/or between types of hospitals; and by examining potential predicting factors
      of turnover among registered nurses. METHODS: A national phone survey was
      undertaken in Israel consisting of a random sampling of registered nurses of
      working age (up to age 60). The subjects comprised 10% of a national database of
      32,000 registered nurses. RESULTS: The turnover rate among working nurses in
      Israel currently stands at 23%. In addition, 13% of employed nurses have taken a
      temporary leave of absence for a period greater than 6 months in the past 10
      years, most up to 1 year. While job satisfaction rates were relatively high
      (72%), Professional satisfaction rates were 60% with no significant difference
      between hospital and community nurses. The turnover rate of registered nurses
      from a hospital setting to the community was significantly higher (p<.01) than
      that of community registered nurses to hospitals. Predicting factors of turnover
      were found to be: young age, part-time work, lack of advanced professional
      education, academic education and low satisfaction with the nursing profession.
      CONCLUSIONS: The shift of nursing workforce is mainly from hospitals to community
      health settings. There is a need to monitor and understand the characteristics of
      job and professional satisfaction among hospital nurses in order to implement
      crucial organizational interventions and retain hospital nursing staffs. Since
      young nurses, nurses working part time and nurses with no advanced professional
      and academic education, tend to move more than others, efforts should be targeted
      at these specific groups.

PMID- 22473247
TI  - Experimental and computational studies of pyridine-assisted post-synthesis
      modified air stable covalent-organic frameworks.
AB  - Pyridine-modified COF-10 exhibits enhanced stability in humid air relative to un
      modified COF-10. Solid state NMR and computational studies were used to probe the
      nature of pyridine interactions with the framework. We propose two models for
      pyridine-framework interactions with different stabilities.

PMID- 22473246
TI  - An economic analysis of tobacco elimination policies in Turkey.
AB  - OBJECTIVE: We aim to evaluate the costs and benefits of various tobacco
      elimination policies, specifically, an immediate taxation option and eight tax
      combined long-term cessation programs. METHODS: We combine demographic
      projections for the period 2012-2050 with incidence and mortality rates of four
      major cigarette related diseases, price elasticity of cigarette demand and unit
      costs of nonprice measures to reduce demand in order to estimate the net present
      discounted values of policy alternatives. RESULTS: The tax-combined cessation
      programs yield lower net costs to households and the society when they phase out
      smoking earlier. However, immediate taxation option is found to be superior, for
      both households and the society, to all tax-combined cessation programs
      irrespective of the duration of intervention. While all policies are estimated to
      yield significant reductions in the expected number of smoking related diseases
      and deaths, a class-based 20-year intervention is found to be the most effective
      program. CONCLUSIONS: Although immediate taxation policy and tax-combined class
      based 20-year intervention program emerge as the best tobacco elimination
      policies for the society, more research is needed on assessing the cost
      effectiveness, applicability and social desirability of these alternatives and on
      designing additional policies to overcome their limitations.

PMID- 22473248
TI  - Endpoints of drug discovery for menopausal vasomotor symptoms:  interpretation of
      data from a proxy of disease.
AB  - OBJECTIVE: Estrogen supplementation is considered a reliable therapeutic approach
      to symptoms of vasomotor dysregulation (hot flashes) associated with the
      menopausal transition and sex hormone deprivation. Implication of changes in
      central neurotransmission in the pathogenesis of hot flashes has prompted the off
      label use of serotonergic and gamma-aminobutyric acid-ergic drugs as a
      therapeutic alternative, claiming similarity of outcomes to those of estrogen
      treatment. METHODS: Using telemetric recordings in a rat model of estrogen
      deficit-induced vasomotor dysregulation, we compared the long- and short-term
      effects of estrogen supplementation and treatment with neuropharmaceuticals
      (venlafaxine, desvenlafaxine, fluoxetine, agomelatine, gabapentin) on endpoints
      of thermoregulation. RESULTS: Among the tested drugs, only fluoxetine was capable
      to emulate the restorative action of estradiol on the diurnal oscillations in
      skin temperature and control of heat dissipation. Unlike estradiol, several of
      the tested compounds produced marked transient decreases in skin temperature
      within the first 2 hours of application while being unable to restore
      physiological diurnal patterns of thermoregulation. CONCLUSIONS: Our findings
      suggest that in this animal model of impaired thermoregulation,
      neuropharmaceuticals may simulate therapeutic effects by eliciting immediate but
      transient hypothermia, which is not associated with the recovery of physiological
      control of heat dissipation. Therefore, short-term monitoring of drug actions in
      this disease model may considerably bias readouts of drug discovery for
      menopausal vasomotor symptoms.

PMID- 22473249
TI  - Effect of hormone therapy on postural balance in postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to analyze the effects of hormone therapy
      (HT) on postural balance in postmenopausal women and its association with risk of
      falls. METHODS: In this cross-sectional study, a total of 225 Brazilian
      postmenopausal women aged 45 to 75 years were included and divided into two
      groups: HT users (n = 102) and nonusers (n = 123). HT users were women who had
      continuously taken HT throughout the preceding 6 months, whereas nonusers
      received no such therapy during the same period. Women with amenorrhea for more
      than 12 months and aged 45 years or older were included. Those with neurological
      or musculoskeletal disorders, vestibulopathies, uncorrected visual deficit, or
      drug use that could affect balance were excluded. Histories of falls (previous 24
      mo) as well as clinical and anthropometric characteristics were analyzed.
      Postural balance was assessed through stabilometry (computerized force platform),
      Romberg test, and crouching test. Statistical analysis included the median test,
      chi test, Spearman correlation coefficient, and logistic regression method (odds
      ratio). RESULTS: Women users of HT were younger (53.0 vs 57.0 y) and with a
      shorter time since menopause (5.5 vs 10.0 y) than nonusers (P < 0.05). No
      anthropometric differences were observed. The number of women who had experienced
      falls was significantly lower among HT users than nonusers: 51 vs 88 falls,
      respectively (P < 0.05), and presented an adjusted risk of falls of 0.49 (95% CI,
      0.27-0.88) times lower than the nonusers group. For the stabilometric parameters,
      HT users showed significantly lower amplitude in body oscillation (latero-lateral
      and antero-posterior) and a smaller oscillation area compared with nonusers (P <
      0.05). There was no significant correlation between the Romberg test and fall
      rate (P > 0.05). In the crouching test, 47.1% of the participants showed an
      adequate level of muscle strength in lower limbs without differences between the
      groups (P > 0.05). CONCLUSIONS: Postmenopausal women using HT showed lower
      frequency of falls and a better performance in stabilometric parameters than did
      nonusers.

PMID- 22473250
TI  - The effects of lifestyle interventions in dynapenic-obese postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to investigate the impact of caloric
      restriction (CR) and resistance training (RT) on body composition, metabolic
      profile and physical capacity in dynapenic-obese postmenopausal women. METHODS:
      Thirty-eight dynapenic-obese postmenopausal (age, 62.6 +/- 4.1 y) women were
      randomly assigned to one of four groups (1, CR; 2, RT; 3, CR + RT; and 4,
      control) for a 12-week intervention. The independent variables were body weight,
      fat mass, and lean body mass (using dual-energy x-ray absorptiometry), waist
      circumference, fasting lipids and glucose, resting systolic and diastolic blood
      pressure, and physical capacity (6-min walk, chair stand, and one-leg stand
      tests). RESULTS: Body weight, fat mass, and waist circumference decreased
      similarly in the CR and CR + RT groups (all P <= 0.05). However, only changes in
      the CR + RT group were significantly different from the control group (all P <=
      0.05). Total cholesterol, triglycerides, and systolic and diastolic blood
      pressure significantly decreased in the CR group (all P <= 0.05); whereas total
      cholesterol, low-density lipoprotein cholesterol, and systolic blood pressure
      decreased in the CR + RT group (P <= 0.05). Physical capacity improved
      significantly in the RT and CR + RT groups (all P <= 0.05), with significant
      greater improvements in the RT group (P <= 0.05). CONCLUSIONS: Our results
      suggest that CR with or without RT is effective in improving metabolic profile,
      whereas RT is effective in improving physical capacity. The combination of RT and
      CR may be particularly relevant in maximizing improvements in physical capacity
      in dynapenic-obese postmenopausal women.

PMID- 22473251
TI  - Phylogeographic patterns of genetic diversity in eastern Mediterranean water
      frogs have been determined by geological processes and climate change in the Late
      Cenozoic.
AB  - AIM: Our aims were to assess the phylogeographic patterns of genetic diversity in
      eastern Mediterranean water frogs and to estimate divergence times using
      different geological scenarios. We related divergence times to past geological
      events and discuss the relevance of our data for the systematics of eastern
      Mediterranean water frogs.  LOCATION: The eastern Mediterranean region.  METHODS:
      Genetic diversity and divergence were calculated using sequences of two protein
      coding mitochondrial (mt) genes: ND2 (1038 bp, 119 sequences) and ND3 (340 bp,
      612 sequences). Divergence times were estimated in a Bayesian framework under
      four geological scenarios representing alternative possible geological histories
      for the eastern Mediterranean. We then compared the different scenarios using
      Bayes factors and additional geological data.  RESULTS: Extensive genetic
      diversity in mtDNA divides eastern Mediterranean water frogs into six main
      haplogroups (MHG). Three MHGs were identified on the Anatolian mainland; the most
      widespread MHG with the highest diversity is distributed from western Anatolia to
      the northern shore of the Caspian Sea, including the type locality of Pelophylax
      ridibundus. The other two Anatolian MHGs are restricted to south-eastern Turkey,
      occupying localities west and east of the Amanos mountain range. One of the
      remaining three MHGs is restricted to Cyprus; a second to the Levant; the third
      was found in the distribution area of European lake frogs (P. ridibundus group),
      including the Balkans.  MAIN CONCLUSIONS: Based on geological evidence and
      estimates of genetic divergence we hypothesize that the water frogs of Cyprus
      have been isolated from the Anatolian mainland populations since the end of the
      Messinian salinity crisis (MSC), i.e. since c. 5.5-5.3 Ma, while our divergence
      time estimates indicate that the isolation of Crete from the mainland populations
      (Peloponnese, Anatolia) most likely pre-dates the MSC. The observed rates of
      divergence imply a time window of c. 1.6-1.1 million years for diversification of
      the largest Anatolian MHG; divergence between the two other Anatolian MHGs may
      have begun about 3.0 Ma, apparently as a result of uplift of the Amanos
      Mountains. Our mtDNA data suggest that the Anatolian water frogs and frogs from
      Cyprus represent several undescribed species.

PMID- 22473252
TI  - Synthesis of functionalized thiophenes and oligothiophenes by selective and
      iterative cross-coupling reactions using indium organometallics.
AB  - The synthesis of unsymmetrical 2,5-disubstituted thiophenes by selective and
      sequential palladium-catalyzed cross-coupling reactions of indium organometallics
      with 2,5-dibromothiophene is reported. Following an iterative coupling sequence,
      alpha-oligothiophenes were synthesized in good yields and with high atom economy.

PMID- 22473255
TI  - Advancing resuscitation science.
AB  - PURPOSE OF REVIEW: To describe an alternative approach for improving survival of
      patients with out-of-hospital cardiac arrest (OHCA). The survival of patients
      with OHCA has been poor and relatively unchanged for decades in spite of
      recurrent national and international guidelines. Although there are exceptions,
      many thought and continue to think that any change in the guidelines for
      cardiopulmonary resuscitation should be based on randomized controlled trials in
      humans. However, many factors, including the need for informed consent, the
      marked variability of patients, and the variability of the type and quality of
      bystander and advanced resuscitation efforts, all make such studies problematic.
      Thus, potentially life-saving procedures are often withheld for decades,
      resulting in unnecessary loss of life. RECENT FINDINGS: Many improvements in
      public health conditions have been made using models of continuous quality
      improvement. When applied to resuscitation science, once baseline data are
      obtained, changes based on reliable experimental findings are instituted and
      outcomes measured. This approach has now been shown to result in significant
      improvement in neurologically intact survival of patients with OHCA. SUMMARY:
      Following this model, we found significant improvement in survival of patients
      with a witnessed OHCA primary cardiac arrest.

PMID- 22473253
TI  - Long-term follow-up of patients with monoclonal gammopathy of undetermined
      significance after kidney transplantation.
AB  - INTRODUCTION: Long-term data regarding kidney transplantation (KTx) patients with
      monoclonal gammopathy of undetermined significance (MGUS) are scarce. We
      evaluated the long-term outcomes of these patients in a single-center
      retrospective study from the Mayo Clinic, Rochester, Minn., USA. METHODS:
      Patients who had an MGUS before transplant or developed one after KTx were
      selected. Monoclonal protein was screened as part of the KTx evaluation by serum
      protein electrophoresis. Screening for posttransplant lymphoproliferative
      disorder (PTLD) or MGUS after transplant was not required by protocol. Patients
      with multiple myeloma, dysproteinemia-related kidney disease or no pretransplant
      serum protein electrophoresis were excluded. RESULTS: Between 1963 and 2006,
      3,518 patients underwent KTx. MGUS was identified in 42 patients, with 23 before
      transplant and 19 after transplant. Median follow-up for these patients was 8.5
      years (range 0.3-37). Four (17.4%) pretransplant MGUS patients developed a
      hematologic malignancy: 2 smoldering multiple myeloma and 2 PTLD - an Epstein
      Barr virus-positive diffuse large cell lymphoma and a Hodgkin lymphoma. None of
      the 19 patients who developed an MGUS after transplant progressed to multiple
      myeloma, but 2 (10.5%) developed Epstein-Barr virus-negative T cell
      lymphoproliferative disorders at 16 and 26 years after transplant. Median
      survival was 26.1 and 28.0 years for the pretransplant and posttransplant MGUS
      groups, respectively. CONCLUSION: Progression from true MGUS to multiple myeloma
      is rare after KTx. KTx appears safe in true MGUS patients if the monoclonal
      gammopathy was not the cause of the kidney disease. None of the patients
      progressed to multiple myeloma, but 2 developed smoldering multiple myeloma and
      several developed PTLD. Further studies are needed to explain the relationship
      between MGUS and PTLD.

PMID- 22473256
TI  - Heart lung interactions during mechanical ventilation.
AB  - PURPOSE OF REVIEW: To survey the recent medical literature examining studies of
      the hemodynamic effects of mechanical ventilation. RECENT FINDINGS: Ventilation
      induced dynamic changes in arterial pulse pressure and stroke volume variation
      (PPV and SVV, respectively) identify volume responsiveness. The cause of PPV and
      SVV are due to intrathoracic pressure-induced variations in right atrial pressure
      changing intrathoracic blood volume over the ventilatory cycle. This explains why
      PPV and SVV are inaccurate with smaller tidal volumes used in acute lung injury,
      but remain useful in one-lung ventilation and prone positioning. Noninvasive
      measures of PPV and SVV using finger plethysmography and aortic root ultrasound
      or estimates of intrathoracic blood volume by thoracic impedance also predict
      volume responsiveness. Finally, the PPV-to-SVV ratio varies with vasomotor tone
      and can be used to identify vasopressor need in hypotensive patients. The
      clinical implications of these findings are starting to be realized in
      recommended management principles. SUMMARY: PPV and SVV predict volume
      responsiveness, but like all monitoring approaches, need to be understood within
      the framework of their physiologic determinations.

PMID- 22473257
TI  - The holistic view on perfusion monitoring in septic shock.
AB  - PURPOSE OF REVIEW: To review recent evidence concerning the interactions between
      hemodynamic and perfusion parameters during septic shock resuscitation, and to
      propose some basic foundations for a more comprehensive perfusion assessment.
      RECENT FINDINGS: Several recent studies have expanded our knowledge about the
      physiologic determinants and limitations of currently used perfusion parameters
      such as central venous oxygen saturation and lactate. Macrohemodynamic,
      metabolic, peripheral and microcirculatory parameters tend to change in parallel
      in response to fluid loading during initial resuscitation. In contrast, perfusion
      markers are poorly correlated in patients who evolve with a persistent
      circulatory dysfunction. Therefore, assessment of perfusion status based solely
      on a single parameter can lead to inaccurate or misleading conclusions. SUMMARY:
      All individual perfusion parameters have extensive limitations to adequately
      reflect tissue perfusion during persistent sepsis-related circulatory
      dysfunction. A multimodal approach integrating macrohemodynamic, metabolic,
      peripheral and eventually microcirculatory perfusion parameters may overcome
      those limitations. This approach may also provide a thorough understanding on the
      predominant driving forces of hypoperfusion, and lead to physiologically oriented
      interventions.

PMID- 22473258
TI  - Prophylaxis against thromboembolism in neurosurgical and head injury patients.
AB  - Neurosurgical patients are at great risk for venous thromboembolism.
      Thromboprophylaxis is either with unfractionated heparin or low molecular weight
      heparin (LMWH). In neurosurgery, this is a matter of debate because of fear from
      bleeding. Few randomized studies show that chemical prophylaxis is safe after
      elective neurosurgeries. Prophylaxis with gradual elastic stocking and venous
      pump may be affective but there are not enough studies and trials examining their
      efficacy. Larger trials are needed to examine the safety of unfractionated
      heparin versus LMWH in neurosurgical patients including head injury patients.

PMID- 22473259
TI  - Anticonvulsant action of anandamide in an in vitro model of epilepsy.
AB  - OBJECTIVE: In both in vitro and in vivo models of epilepsy, cannabinoids had anti
      convulsant properties, which have been shown to be mediated through activation of
      central cannabinoid type 1 receptors (CB1). The current study used 24 adult
      Sprague Dawley rats to investigate the effects of endogenously occurring
      cannabinoids (endocannabinoids) on epileptiform activity induced by picrotoxin.
      METHODS: We carried out the study at King Fahad Medical Research Center, Jeddah,
      Kingdom of Saudi Arabia in September 2004. We made extracellular recordings from
      stratum pyramidale of the CA1 region of hippocampal slices maintained in a
      submersion type recording chamber. Stimulation with single pulses, evoked
      population spikes of approximately equal amplitude. RESULTS: Using single pulse
      stimulation, perfusion of 0.5 uM picrotoxin caused a small increase in the
      amplitude of the first population spike, and caused epilepsy by introducing a
      second or multiple population spikes. In the presence of picrotoxin, anandamide
      reduced the amplitude of both the first population spike (PS1) and the second
      population spike (PS2), thus reducing the epilepsy. The CB1 receptor antagonist,
      AM281 (500 nM) had no effect on responses recorded in the presence of picrotoxin,
      but totally blocked the effect of subsequently perfused anandamide. CONCLUSION:
      The results showed that anandamide caused an anti-convulsant effect. Furthermore,
      these results implicate the cannabinoid CB1 receptor as a major endogenous site
      of seizure modulation.

PMID- 22473260
TI  - Comparison of blood lead levels in 1-7 year old children with and without
      seizure.
AB  - OBJECTIVE: Lead is a nonessential metal and is not a natural constituent in
      humans. Lead is very toxic for children, especially to the central nervous
      system. We studied and compared blood lead levels in children aged 1-7 years old
      with and without convulsions. METHODS: In this study we randomly measured blood
      lead levels in 206 children referred to Imam Reza Hospital, Pediatric Emergency
      Ward and Outpatient Clinic, Mashad, Iran from December 2001 to June 2003. There
      were 95 children with convulsions and 111 without convulsions. RESULTS: There
      were no significant differences in the mean value of age, place of residence and
      economic status between the 2 groups (P values were 0.20 for age, 0.14 for place
      of residence and 0.76 for economic status). The mean blood lead level +/- SD in
      the convulsive group was 126.53 +/- 35.91 ug/lit and in the non-convulsive group
      was 118.03 +/- 32.10 ug/lit (p = 0.70). CONCLUSION: This study showed that the
      blood lead levels in convulsive patients is not statistically significant
      compared to the non-convulsive group and routine measurement is not advised.

PMID- 22473261
TI  - Heavy metals and trace elements in hair samples of autistic children in central
      Saudi Arabia.
AB  - OBJECTIVE: Autism a childhood neurodevelopmental disorder, with onset prior to 36
      months old. The etiology of autism is complex, and usually, the underlying
      pathologic mechanisms are unknown. Recently, alteration in heavy metals and trace
      elements had some interest. The aim of the present study is to examine levels of
      trace elements and heavy metals in hair samples, of autism spectrum disorders in
      the Riyadh area. METHODS: The study was conducted in Riyadh area, Kingdom of
      Saudi Arabia between September 2003 and April 2004. Seventy-seven autistic
      children participated in the study, all with confirmed diagnosis according to E-2
      diagnostic criteria for autistic spectrum disorders. Hair samples were analyzed
      by atomic absorption spectrophotometer.  The measurements of 9 heavy metals
      (lead, mercury, aluminum, arsenic, barium, cadmium, nickel, antimony and
      strontium), and 11 trace elements (sodium, calcium, chromium, copper, iron,
      magnesium, manganese, zinc, cobalt, selenium and molybdenum) was carried out.
      RESULTS: The current study showed significantly higher levels of toxic heavy
      metals mercury, lead, arsenic, antimony and cadmium in autistic spectrum
      disorders as compared to the control children. Moreover, hair samples from
      children with autistic spectrum disorders contained significantly lower
      concentrations of calcium, copper, chromium, manganese, iron and cobalt, as
      compared to normal children. In addition, we found a significantly higher
      incidence of social withdrawal, sleeping and eating disorders, speech and
      language disorders among autism spectrum disorders as compared to controls.
      CONCLUSION: The present study demonstrated alteration in levels of toxic heavy
      metals and essential trace elements in children with autistic spectrum disorders
      as compared to normal children. This suggests a possible pathophysiological role
      of heavy metals and trace elements in the genesis of symptoms of autism spectrum
      disorders, such as social withdrawal, eating and sleeping disorders. In turn,
      those children with autistic spectrum disorders might benefit from chelating
      therapy for heavy metal poisoning and supplementation of essential trace
      elements.

PMID- 22473262
TI  - The effect of Khat (Catha edulis) on acute cerebral infarction.
AB  - OBJECTIVE: The aim of this study was to show the effects of Khat on acute
      cerebral infarction (ACI), specifically regarding blood pressure, age and gender,
      and to open the door for further neurological research. METHODS: We collected 358
      patients with ACI, and 335 volunteers from Al-Thowra Modern General Hospital in
      Sana'a, Yemen, and Thamar General Hospital, Thamar City, approximately 100 km
      south of Sana'a. During a one year period, from February 2003 to March 2004, we
      conducted research regarding blood pressure, age, and gender related to the
      chewing or not chewing of Khat. We conducted a comparison between the ACI group
      and the volunteer group, using the SPSS 10.0 Chi-square statistical methods.
      RESULTS: Results show that Khat increases blood pressure in patients with ACI.
      The gender-related effects show that Khat affects a greater percentage of males
      (74.6%) compared to females (25.4%), Khat chewers in the patient group showed a
      statistical significance of p<0.001. The 358 ACI patients had a mean age of 51.5
      years old, while in the 335 normal individuals the mean age was 42.5 years old,
      showing a statistical significance of p<0.001. CONCLUSION: Khat is a risk to
      blood pressure in ACI patients, with a statistical significance of p<0.001. Khat
      effects males more than females, and Khat chewers are more affected than non
      chewers with a statistical significance of p<0.01. Khat also shows a significant
      relationship with age, affecting older persons (p<0.001).

PMID- 22473263
TI  - Multiple sclerosis in Oman.
AB  - OBJECTIVE: To describe the clinical characteristics of multiple sclerosis (MS)
      seen in Oman and compare it with those seen in the Arabian peninsula, the rest of
      Asia and the Western world. METHODS: A hospital based case descriptive study of
      MS patients, seen at Sultan Qaboos University Hospital in the Sultanate of Oman,
      between June 1990- June 2000. RESULTS: We saw a total of 30 patients during the
      study period, with a prevalence of 4/100,000. Mean age at onset was 27 and male
      to female ratio was 1.1:1. Visual and motor symptoms were the most common
      presenting features. Lesions were distributed in the optic nerve in 17, spinal
      cord in 16, cerebral hemispheres in 12 and brain stem and cerebellum in 10. One
      third of patients had the optico-spinal form of the disease. Twenty-three
      patients had a remitting and relapsing course, 4 had secondary progressive and 3
      had a primary progressive course. Cerebrospinal fluid oligoclonal band was
      positive only in 20% of patients, and we carried out HLA analysis in 24 of these
      patients. CONCLUSION: The incidence of MS is low in Oman, but similar to other
      countries in the region. The optico-spinal form of the disease constituted 30% in
      this series, comparable to other series reported from Asia. Generally, the
      clinical profile of MS seen in Oman is very similar to those reported from the
      Arabian Peninsula and other Asian regions.

PMID- 22473264
TI  - Neurocysticercosis in central Saudi Arabia.
AB  - Neurocysticercosis is a disease endemic in pork breeding societies. It exhibits
      itself by the sudden development of seizures in an apparently healthy individual,
      a rather nonspecific symptom. In its own cultural circles, diagnosis is easy
      because of the higher incidence and prevalence of the ailment. However in
      cultures whose religion excludes the breeding of pork, such as Islamic countries,
      diagnosis depends on an often forgotten spiritual history, which we believe may
      have a place as the fourth epidemiologic criterion in the revised diagnostic
      criteria for neurocysticercosis.

PMID- 22473265
TI  - Isoniazid intoxication. Light and electron microscopic findings in muscle and
      sural nerve biopsies.
AB  - This study indicates the cellular and ultrastructural changes of the thigh muscle
      and sural nerve biopsies of a patient intoxicated as a result of isoniazid intake
      for tuberculosis treatment.  The observation of the relative degradation of
      myelination and fibre type II groups was apparent.  The regular concentric layers
      of the myelin sheath were destroyed.  There was a consistent increase in
      irregular vacuolization and membranous structures in the axon and the cytoplasm
      of the Schwan cells.  It is concluded that poisoning cannot be attributed solely
      to the axonal degradation but also to the direct toxic effect of the drug.

PMID- 22473266
TI  - Spontaneous cerebrospinal fluid rhinorrhea through clival defect.
AB  - Spontaneous cerebrospinal fluid fistula secondary to clival defect is a very rare
      condition. Only 2 cases are reported previously in the literature. We report a
      case of clival defect in a young male patient presenting with spontaneous
      cerebrospinal fluid rhinorrhea which failed detection by conventional CT and MRI.
      The patient was referred to our center after failed anterior cranial fossa
      repair. Thorough radiological investigations successfully detected the defect in
      the posterior wall of the sphenoid sinus 5 mm distal to the posterior limit of
      the floor of the sella just on the midline. The fistula was managed successfully
      through an endonasal transsphenoidal approach. We present the case reviewing the
      literature concerning the pathophysiology of spontaneous cerebrospinal fluid
      fistula through the sphenoid sinus.

PMID- 22473267
TI  - Brain metastasis as an initial manifestation of a gallbladder carcinoma.
AB  - Though autopsy studies demonstrated 5% metastasis to the brain, clinical
      presentation of a central nervous system metastasis from gallbladder cancer is
      rare. We report a case of a 72-year-old woman who initially presented with a
      solitary brain metastasis from an adenocarcinoma of the gallbladder, which was
      diagnosed pre-operatively as glioblastoma multiforme. This is the second of such
      a case in the English literature. We emphasize the importance of including
      metastasis in the differential diagnosis of single intracranial tumor for proper
      planning of patient management.

PMID- 22473268
TI  - Concurrent Poland anomaly and idiopathic hirsutism.
AB  - Poland syndrome is characterized by congenital and unilateral absence of the
      pectoralis major muscle and ipsilateral upper limb anomalies. Identified patients
      also may include other disorders. We report a 15-year-old Caucasian woman with a
      unilateral hypoplasia of the breast and nipple, ipsilateral chest wall depression
      deformity, pectoralis major muscle agenesis, and severe hirsutism (Ferriman
      Gallwey score: 21) without extremity anomaly. She had regular menses, and no
      hormonal abnormality and family history of hirsutism. Therefore, she was
      considered as a case of idiopathic hirsutism. This is the first case report of
      hirsutism in a patient with Poland syndrome.

PMID- 22473269
TI  - Hyperglycemia - induced by Olanzapine.

PMID- 22473271
TI  - A distinictive EEG pattern.

PMID- 22473270
TI  - A study on association between dissociation and dreaming in patients with major
      depressive disorder.

PMID- 22473272
TI  - "I have to turn myself inside out": caring for immigrant families of children
      with asthma.
AB  - In multicultural societies, health care professionals encounter immigrant
      families of children with asthma. They play an important role in supporting these
      families, but few studies have focused on this phenomenon. The aim of the present
      study is to gain a broader understanding of the challenges health care
      professionals face in their encounters with non-Western immigrant parents of
      children with asthma. Seventeen professional caregivers were interviewed, and
      their narratives were analyzed using qualitative content analysis. The results
      show that health care professionals' main challenges when encountering immigrant
      parents can be described by the theme, "Turning oneself inside out." This theme
      is characterized by five categories: gender and professional issues, impact on
      professional relationships, communication challenges, unfamiliar disease and
      treatment perceptions, and time issues. The results highlight the importance of
      providing health care professionals with support and organizational conditions
      that increase opportunities to understand the unique situation of these families.

PMID- 22473273
TI  - Anxiety, depression, and self-management: a systematic review.
AB  - The purpose of this article was to address the clinically relevant question: In
      the presence of anxiety and/or depression, do patients who have had heart surgery
      engage in self-management behaviors following hospital discharge? A systematic
      review of 16 studies that examined the psychological condition of patients who
      had coronary artery bypass graft (CABG) and/or valvular replacement surgery was
      conducted. Moderate to severe levels of anxiety and depression exist during the
      first month of home recovery and appear to have an effect on performance of self
      management behaviors. As the influence of patients' psychological condition is
      continued to be examined, it is imperative for health care providers to manage
      increased rates of anxiety and/or depression following heart surgery. Music and
      relaxation therapy are presented as evidenced based recommendations for managing
      anxiety and depression in patients following heart surgery.

PMID- 22473274
TI  - Challenges to hospital discharge planning for older adults.
AB  - Hospital discharge planning for older adults is an essential component to
      successful transitional care and will become increasingly important as hospitals
      face financial penalties for avoidable readmissions. This study reports a cross
      sectional descriptive web-based survey study about challenges to discharge
      planning experienced by hospitals in the Midwestern state of Missouri. Problems
      identified by respondents included difficulties finding placement for patients
      requiring ventilator care, hemodialysis, chemotherapy, radiation therapy, wound
      vacuums, or who have mental health care needs. In general, urban hospitals
      reported more problems with finding postacute discharge destinations for patients
      than did rural hospitals. It is essential that nursing homes, residential care
      facilities, and home health agencies be adequately reimbursed to manage complex
      patients. It may be equally important to identify ways to develop critical
      assessment and care management skills that are needed in postacute staff to
      increase the likelihood that patients will be accepted at the time of hospital
      discharge.

PMID- 22473275
TI  - Cross-cultural adaptation of an intimate partner violence questionnaire.
AB  - The aim of this study was to describe the translation and the cross-cultural
      adaptation process of questionnaire about intimate partner violence (IPV). IPV is
      a serious threat to women's health. There is a need for instruments to measure
      the results of educational interventions. The Violence Against Women Health Care
      Provider Survey was found suitable for translation and adaptation to the Swedish
      cultural context. A five-step process according to Guillemin et al. was followed:
      (a) translation by independent translators, (b) back translation of each
      translation independently from each other, (c) committee review with
      multidisciplinary members produces the final version, and (d) pretesting to
      ensure equivalence between source and final version, and (e) weighting scores.
      The Swedish version consisted of the same number of items as the original. The
      results indicated that the questionnaire can be used in Sweden to measure the
      effectiveness of IPV training programs.

PMID- 22473276
TI  - Systematic review and meta-analysis of cutting diathermy versus scalpel for skin
      incision (Br J Surg 2012; 99: 613-620).

PMID- 22473277
TI  - Explaining the decrease in mortality from abdominal aortic aneurysm rupture.
AB  - BACKGROUND: A steady rise in mortality from abdominal aortic aneurysm (AAA) was
      reported in the 1980s and 1990 s, although this is now declining rapidly. Reasons
      for the recent decline in mortality from AAA rupture are investigated here.
      METHODS: Routine statistics for mortality, hospital admissions and procedures in
      England and Wales were investigated. All data were age-standardized. Trends in
      smoking, hypertension and treatment for hypercholesterolaemia (statins), together
      with regression coefficients for mortality, were available from public sources
      for those aged at least 65 years. Deaths from ruptured AAA avoided in this age
      group were estimated by using the IMPACT equation: deaths avoided = (deaths in
      index year) * (risk factor decline) * beta-coefficient. RESULTS: From 1997,
      deaths from ruptured AAA have decreased sharply, almost twofold in men. Hospital
      admissions for elective AAA repair have increased modestly (from 40 to 45 per
      100,000 population), attributable entirely to more procedures in those aged 75
      years and over (P < 0.001). Admissions for ruptured AAA have declined from 18.6
      to 13.5 per 100,000 population, across all ages, with the proportion offered and
      surviving emergency repair unchanged. From 1997, mortality from ruptured aneurysm
      in those aged at least 65 years has fallen from 65.9 to 44.6 per 100,000
      population. An estimated 8-11 deaths per 100,000 population were avoided by a
      reduced prevalence of smoking and a similar number from an increase in the number
      of elective AAA repairs. Estimates for the effects of blood pressure and lipid
      control are uncertain. CONCLUSION: The reduction in incidence of ruptured AAA
      since 1997 is attributable largely to changes in smoking prevalence and increases
      in elective AAA repair in those aged 75 years and over.

PMID- 22473278
TI  - Explaining the decrease in mortality from abdominal aortic aneurysm rupture (Br J
      Surg 2012; 99: 637-645).

PMID- 22473280
TI  - Late results of endoscopic thoracic sympathectomy for hyperhidrosis and facial
      blushing (Br J Surg 2011; 98: 1719-1724).

PMID- 22473279
TI  - Regional variation in the incidence of abdominal aortic aneurysm in Sweden (Br J
      Surg 2012; 99: 647-653).

PMID- 22473281
TI  - Multicentre observational study of the natural history of left-sided acute
      diverticulitis (Br J Surg 2012; 99: 276-285) (Br J Surg 2012; 99: 285-286).

PMID- 22473284
TI  - Surgical wisdom (Br J Surg 2012; 99: 3-5).

PMID- 22473286
TI  - Chorioretinitis as a first sign of SSPE.
AB  - Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative
      disorder. Ocular involvement in SSPE has been well known and might be seen in 42
      to 50% of the patients. Visual findings are generally seen at stage III with
      neurological abnormalities. Ophthalmologic involvement might be preceding typical
      SSPE symptoms.

PMID- 22473287
TI  - Chondromyxoid fibroma of the anterior skull base invading the orbit in a
      pediatric patient: case report and review of the literature.
AB  - Chondromyxoid fibroma (CMF) is a rare bone tumor of cartilaginous derivation
      representing less than 1% of all benign bone neoplasms. It is a slow-growing,
      locally destructive tumor that usually affects the metaphyseal region of long
      bones of patients in their second or third decade of life. Involvement of the
      skull base and orbit is extremely rare. We present the first case of
      histopathology-proven CMF originating in the greater sphenoid wing and extending
      into the orbit in a 14-year-old boy. He complained of pain and swelling of his
      left lateral orbit for 4 months and had 3-mm nonaxial proptosis. Magnetic
      resonance imaging of the orbit revealed a well-defined lesion in the lateral wall
      of the left orbit, hypointense on T1-weighted images, and heterogenous
      hyperintense on T2-weighted images and enhanced after contrast media injection.
      Through a left semicoronal skin incision, the mass was removed totally and the
      lateral orbital wall was reconstructed. The clinical manifestations, imaging
      findings, and surgical treatment of the lesion are discussed with a review of the
      literature.

PMID- 22473288
TI  - A 1.1 million base pair X-chromosomal deletion covering the PDHA1 and CDKL5 genes
      in a female patient with West syndrome and pyruvate oxidation deficiency.
AB  - Mutations in the X-linked E1alpha subunit of the pyruvate dehydrogenase complex
      (PHDC) are the most frequent causes of PDHC deficiency. The clinical picture is
      heterogeneous depending on residual enzyme activity and X-inactivation. We report
      on a girl who presented at an age of 3 weeks with muscular hypotonia, vomiting,
      hyperlactatemia, microcephaly, enlarged ventricles, partial agenesis of the
      corpus callosum, and seizures. PDHA1 sequencing was normal in DNA from blood. In
      muscle, normal PDHC activity was measured while substrate oxidation rates
      revealed moderately diminished pyruvate oxidation. Quantitative PCR analysis
      revealed hemizygosity of the whole PDHA1 gene. Homozygosity mapping and
      determination of the breakpoint showed a 1.1 million base pair deletion on the X
      chromosome including the CDKL5 and PDHA1 genes. The difficulty in the diagnosis
      of PDHC deficiency is evident: (1) enzyme activity can be normal depending on the
      X-inactivation; (2) large deletions can be missed by routine genetic analysis;
      and (3) only quantification of the PDHA1 gene content revealed the mutation in
      our patient. We recommend to revisit patients who are clinically suspicious for a
      mitochondrial disorder especially for hidden PDHA1 mutations, such as large
      deletions.

PMID- 22473289
TI  - Centropontine myelinolysis related to refeeding syndrome in an adolescent
      suffering from anorexia nervosa.
AB  - Centropontine myelinolysis (CPM) is a rare neurologic disorder defined by
      symmetric demyelination in the central pons, mostly due to alcoholism,
      malnutrition, or water-electrolyte abnormalities. We report an unusual case of
      CPM likely due to hypophosphatemia, related to a refeeding syndrome in the
      context of mental anorexia. A 15-year-old girl with mental anorexia presented
      with hypophosphatemia in the following days of enteral refeeding, and then
      suffered from confusion, neurological signs, and typical MRI lesions of CPM.
      Hypophosphoremia may be considered as a causative agent in CPM related to
      refeeding syndrome. This clinical observation also highlights the importance of
      recognizing patients at high risk of refeeding syndrome to initiate a balanced
      nutrition with careful monitoring.

PMID- 22473290
TI  - Twists and turns in the hierarchical self-assembly pathways of a non-amphiphilic
      chiral supramolecular material.
AB  - The formation of helical self-assembled fibres by a C(3) symmetric molecule
      incorporating three tetrathiafulvalene units is shown to be influenced
      dramatically by the processing conditions, leading to a variety of different
      chiral forms, including unprecedented croissants.

PMID- 22473291
TI  - Spatiotemporal dynamics of neural activity related to auditory induction in the
      core and belt fields of guinea-pig auditory cortex.
AB  - Auditory induction is a continuity illusion in which missing sounds are perceived
      under appropriate conditions, for example, when noise is inserted during silent
      gaps in the sound. To elucidate the neural mechanisms underlying auditory
      induction, neural responses to tones interrupted by a silent gap or noise were
      examined in the core and belt fields of the auditory cortex using real-time
      optical imaging with a voltage-sensitive dye. Tone stimuli interrupted by a
      silent gap elicited responses to the second tone following the gap as well as
      early phasic responses to the first tone. Tone stimuli interrupted by broad-band
      noise (BN), considered to cause auditory induction, considerably reduced or
      eliminated responses to the tone following the noise. This reduction was stronger
      in the dorsocaudal field (field DC) and belt fields compared with the anterior
      field (the primary auditory cortex of guinea pig). Tone stimuli interrupted by
      notched (band-stopped) noise centered at the tone frequency, considered to
      decrease the strength of auditory induction, partially restored the second
      responses from the suppression caused by BN. These results suggest that
      substantial changes between responses to silent gap-inserted tones and those to
      BN-inserted tones emerged in field DC and belt fields. Moreover, the findings
      indicate that field DC is the first area in which these changes emerge,
      suggesting that it may be an important region for auditory induction of simple
      sounds.

PMID- 22473292
TI  - Adhesion molecules close homolog of L1 and tenascin-C affect blood-spinal cord
      barrier repair.
AB  - Mice deficient in the recognition molecules, close homolog of L1 (CHL1) and
      tenascin-C, show improved and reduced functional recovery, respectively, after
      spinal cord injury compared with wild-type littermates. In this study, we
      addressed the question whether the differential functional outcome was paralleled
      by differences in blood-spinal cord barrier (BSCB) repair in the two mouse
      strains. We conducted spinal cord compression injuries in knock-out and wild-type
      mice. BSCB permeability was assessed by measuring the Evans blue spread within
      the spinal cord tissue at 14-21 days after injury. Results show that CHL1 reduces
      and tenascin-C enhances BSCB permeability, suggesting a correlation between
      functional outcome and BSCB repair.

PMID- 22473293
TI  - Exploring the parahippocampal cortex response to high and low spatial frequency
      spaces.
AB  - The posterior parahippocampal cortex (PHC) supports a range of cognitive
      functions, in particular scene processing. However, it has recently been
      suggested that PHC engagement during functional MRI simply reflects the
      representation of three-dimensional local space. If so, PHC should respond to
      space in the absence of scenes, geometric layout, objects or contextual
      associations. It has also been reported that PHC activation may be influenced by
      low-level visual properties of stimuli such as spatial frequency. Here, we tested
      whether PHC was responsive to the mere sense of space in highly simplified
      stimuli, and whether this was affected by their spatial frequency distribution.
      Participants were scanned using functional MRI while viewing depictions of simple
      three-dimensional space, and matched control stimuli that did not depict a space.
      Half the stimuli were low-pass filtered to ascertain the impact of spatial
      frequency. We observed a significant interaction between space and spatial
      frequency in bilateral PHC. Specifically, stimuli depicting space (more than
      nonspatial stimuli) engaged the right PHC when they featured high spatial
      frequencies. In contrast, the interaction in the left PHC did not show a
      preferential response to space. We conclude that a simple depiction of three
      dimensional space that is devoid of objects, scene layouts or contextual
      associations is sufficient to robustly engage the right PHC, at least when high
      spatial frequencies are present. We suggest that coding for the presence of space
      may be a core function of PHC, and could explain its engagement in a range of
      tasks, including scene processing, where space is always present.

PMID- 22473295
TI  - Detection of TNT based on conjugated polymer encapsulated in mesoporous silica
      nanoparticles through FRET.
AB  - Amine-functionalized mesoporous silica nanoparticles containing poly(p
      phenylenevinylene) provide a facile strategy to detect TNT through fluorescence
      resonance energy transfer (FRET). The observed linear fluorescence intensity
      change allows the quantitative detection of TNT with the detection limit of 6 *
      10(-7) M.

PMID- 22473296
TI  - The cost of research in developing countries.

PMID- 22473294
TI  - Laser-capture microdissection and transcriptional profiling of the dorsomedial
      nucleus of the hypothalamus.
AB  - Identifying neuronal molecular markers with restricted patterns of expression is
      a crucial step in dissecting the numerous pathways and functions of the brain.
      While the dorsomedial nucleus of the hypothalamus (DMH) has been implicated in a
      host of physiological processes, current functional studies have been limited by
      the lack of molecular markers specific for DMH. Identification of such markers
      would facilitate the development of mouse models with DMH-specific genetic
      manipulations. Here we used a combination of laser-capture microdissection (LCM)
      and gene expression profiling to identify genes that are highly expressed within
      the DMH relative to adjacent hypothalamic regions. Six of the most highly
      expressed of these genes, Gpr50, 4930511J11Rik, Pcsk5, Grp, Sulf1, and Rorbeta,
      were further characterized by real-time polymerase chain reaction (PCR) analysis
      and in situ hybridization histochemistry. The genes identified in this article
      will provide the basis for future gene-targeted approaches for studying DMH
      function.

PMID- 22473298
TI  - Plant phytochemicals as new potential drugs for immune disorders and cancer
      therapy: really a promising path?
AB  - Plant phytochemicals represent an exciting opportunity to maintain best health
      conditions through a balanced and properly administered daily nutrition or
      dietary supplement and have often been considered a good option for obtaining a
      few promising, expensive new drugs from plants. Several polyphenolic compounds,
      such as resveratrol, tea catechins and flavonoids, which are commonly found in
      vegetables, fruits and plant-derived juices or beverages, exert well-evidenced
      cardioprotective, neuroprotective, chemopreventive and anti-inflammatory
      properties, but, nevertheless, further clinical and epidemiological research is
      required. Most of these botanical byproducts are produced as noxious components
      by plants, in order to prevent pathogen colonization, insect-mediated damage and
      also to discourage animals from eating them. An evolutionary theory of stress
      adaptation would explain how these toxic substances from nature act as protective
      molecules. A future challenge to achieve a rather complete understanding of these
      chemical phenol derivatives for human health should deal with the complexity of
      cellular signalling networks, the epigenetic machinery endowment of the cell and
      the nonlinear relationship between dose and effectiveness.

PMID- 22473299
TI  - Inducing dendritic growth in cultured sympathetic neurons.
AB  - The shape of the dendritic arbor determines the total synaptic input a neuron can
      receive (1-3), and influences the types and distribution of these inputs (4-6).
      Altered patterns of dendritic growth and plasticity are associated with impaired
      neurobehavioral function in experimental models (7), and are thought to
      contribute to clinical symptoms observed in both neurodevelopmental disorders (8
      10) and neurodegenerative diseases (11-13). Such observations underscore the
      functional importance of precisely regulating dendritic morphology, and suggest
      that identifying mechanisms that control dendritic growth will not only advance
      understanding of how neuronal connectivity is regulated during normal
      development, but may also provide insight on novel therapeutic strategies for
      diverse neurological diseases.    Mechanistic studies of dendritic growth would
      be greatly facilitated by the availability of a model system that allows neurons
      to be experimentally switched from a state in which they do not extend dendrites
      to one in which they elaborate a dendritic arbor comparable to that of their in
      vivo counterparts. Primary cultures of sympathetic neurons dissociated from the
      superior cervical ganglia (SCG) of perinatal rodents provide such a model. When
      cultured in defined medium in the absence of serum and ganglionic glial cells,
      sympathetic neurons extend a single process which is axonal, and this unipolar
      state persists for weeks to months in culture (14,15). However, the addition of
      either bone morphogenetic protein-7 (BMP-7) (16,17) or Matrigel (18) to the
      culture medium triggers these neurons to extend multiple processes that meet the
      morphologic, biochemical and functional criteria for dendrites. Sympathetic
      neurons dissociated from the SCG of perinatal rodents and grown under defined
      conditions are a homogenous population of neurons (19) that respond uniformly to
      the dendrite-promoting activity of Matrigel, BMP-7 and other BMPs of the
      decapentaplegic (dpp) and 60A subfamilies (17,18,20,21). Importantly, Matrigel-
      and BMP-induced dendrite formation occurs in the absence of changes in cell
      survival or axonal growth (17,18).    Here, we describe how to set up dissociated
      cultures of sympathetic neurons derived from the SCG of perinatal rats so that
      they are responsive to the selective dendrite-promoting activity of Matrigel or
      BMPs.

PMID- 22473300
TI  - Pregabalin-associated elevation of clozapine serum levels.
AB  - We report our experience with a 34-year-old patient with schizophrenia, paranoid
      subtype, who demonstrated an elevation of clozapine serum levels subsequent to
      pregabalin comedication used for the treatment of schizophrenic anxiety. This
      observation turned to be dose-dependent. Although the pharmacokinetic profile of
      pregabalin suggests an exclusive renal elimination, our report supports the
      presumption of a possible direct or indirect hepatic "effect" of pregabalin.

PMID- 22473297
TI  - The pro-metastatic role of bone marrow-derived cells: a focus on MSCs and
      regulatory T cells.
AB  - Several bone marrow-derived cells have been shown to promote tumour growth and
      progression. These cells can home to the primary tumour and become active
      components of the tumour microenvironment. Recent studies have also identified
      bone marrow-derived cells-such as mesenchymal stem cells and regulatory T cells
      as contributors to cancer metastasis. The innate versatility of these cells
      provides diverse functional aid to promote malignancy, ranging from structural
      support to signal-mediated suppression of the host immune response. Here, we
      review the role of mesenchymal stem cells and regulatory T cells in cancer
      metastasis. A better understanding of the bipolar nature of these bone marrow
      derived cells in physiological and malignant contexts could pave the way for new
      therapeutics against metastatic disease.

PMID- 22473302
TI  - Variation of MODIS reflectance and vegetation indices with viewing geometry and
      soybean development.
AB  - Directional effects introduce a variability in reflectance and vegetation index
      determination, especially when large field-of-view sensors are used (e.g.,
      Moderate Resolution Imaging Spectroradiometer - MODIS). In this study, we
      evaluated directional effects on MODIS reflectance and four vegetation indices
      (Normalized Difference Vegetation Index - NDVI; Enhanced Vegetation Index - EVI;
      Normalized Difference Water Index - NDWI(1640) and NDWI(2120)) with the soybean
      development in two growing seasons (2004-2005 and 2005-2006). To keep the
      reproductive stage for a given cultivar as a constant factor while varying
      viewing geometry, pairs of images obtained in close dates and opposite view
      angles were analyzed. By using a non-parametric statistics with bootstrapping and
      by normalizing these indices for angular differences among viewing directions,
      their sensitivities to directional effects were studied. Results showed that the
      variation in MODIS reflectance between consecutive phenological stages was
      generally smaller than that resultant from viewing geometry for closed canopies.
      The contrary was observed for incomplete canopies. The reflectance of the first
      seven MODIS bands was higher in the backscattering. Except for the EVI, the other
      vegetation indices had larger values in the forward scattering direction.
      Directional effects decreased with canopy closure. The NDVI was lesser affected
      by directional effects than the other indices, presenting the smallest
      differences between viewing directions for fixed phenological stages.

PMID- 22473303
TI  - Chinese manipulation for mechanical neck pain: a systematic review.
AB  - OBJECTIVE: To assess whether Chinese manipulation improves pain,
      function/disability and global perceived effect in adults with
      acute/subacute/chronic neck pain. DATA SOURCES: CAJ Full-text Database (Chinese),
      Wanfang Database (Chinese), Cochrane Database (English) and Medline (English).
      REVIEW METHODS: Literature searching was performed with the following keywords
      and their combination: 'manual therapy/bone setting/Chinese manipulation',
      'neck/cervical pain', 'cervical vertebrae', 'cervical spondylosis/radiculopathy'
      and 'randomized controlled trial/review.' Two independent reviewers selected
      studies, extracted data and assessed risk of bias for each included study.
      Randomized controlled trials or quasi-randomized controlled trials on the effect
      of Chinese manipulation in treating adult patients with neck pain were selected.
      Mean differences with 95% confidence intervals (CI) were calculated. Quality of
      the evidence was assessed by the Grading of Recommendations, Assessment,
      Development and Evaluation (GRADE) approach. RESULTS: Four studies (610
      participants) were included in this review. There was very low-quality evidence
      suggesting that, compared to cervical traction in sitting, Chinese manipulation
      produced more immediate post-intervention pain relief (mean difference: -1.06;
      95% CI: -1.37~ -0.75; P < 0.001) and improvement of global signs and symptoms
      (mean difference: -3.81; 95% CI: -4.71 ~ -2.91; P < 0.001). Very low-quality
      evidence showed that Chinese manipulation alone was superior to Chinese
      traditional massage in immediate post-intervention pain relief (mean difference: 
      2.02; 95% CI: -2.78~ -1.26; P < 0.001). CONCLUSIONS: There was limited evidence
      showing Chinese manipulation could produce short-term improvement for neck pain.

PMID- 22473304
TI  - DC-SCRIPT: AR and VDR regulator lost upon transformation of prostate epithelial
      cells.
AB  - BACKGROUND: Nuclear receptors (NR), including the Androgen Receptor (AR) and the
      Vitamin D Receptor (VDR), play an important role in prostate cancer etiology. We
      recently found that DC-SCRIPT is a prognostic marker in breast cancer and a
      unique NR coregulator differentially regulating different classes of NRs. Here we
      investigated the importance of DC-SCRIPT in prostate cancer. METHODS: DC-SCRIPT
      mRNA expression was measured by qPCR. Immunohistochemistry was used to detect DC
      SCRIPT protein expression. The functional effects of DC-SCRIPT on the
      transcriptional activity of AR and VDR were assessed by luciferase reporter
      assays and qPCR assays on well-known AR and VDR target genes. RESULTS: DC-SCRIPT
      mRNA was higher in normal than in corresponding malignant prostate tissue but
      could not be related to disease stage. DC-SCRIPT protein was found in
      morphologically normal prostate glands and in infiltrating immune cells.
      Strikingly, DC-SCRIPT protein expression was absent in malignant prostate
      epithelial tissue and prostate carcinoma cell lines. DC-SCRIPT protein expression
      appears to be lost prior to the basal cell marker HMW cytokeratin used in
      prostate carcinoma diagnostics. In addition, our data demonstrated that DC-SCRIPT
      repressed transcription mediated by wild-type and mutated AR while enhancing VDR
      mediated transcription. In addition, transient expression of DC-SCRIPT expression
      in prostate carcinoma cells strongly repressed cell growth. CONCLUSIONS: DC
      SCRIPT is a key regulator of nuclear receptors AR and VDR that play an opposite
      role in prostate cancer etiology and loss of DC-SCRIPT may be involved in the
      onset of prostate cancer.

PMID- 22473305
TI  - Enantioselective synthesis of optically active cis-beta-thio-alpha-amino acid
      derivatives through an organocatalytic cascade thio-Michael/ring opening process.
AB  - Non-naturally enantioenriched cis-beta-thio-alpha-amino acid derivatives were
      synthesized through one pot, cascade thio-Michael/ring opening reaction of
      aromatic thiols with (Z)-olefinic azlactones in good yields with high levels of
      diastereoselectivities and enantioselectivities, which was catalyzed by a chiral
      bifunctional thiourea-tertiary amine catalyst.

PMID- 22473306
TI  - CO oxidation over ruthenium: identification of the catalytically active phases at
      near-atmospheric pressures.
AB  - CO oxidation was carried out over Ru(0001) and RuO2(110) thin film grown on
      Ru(0001) at various O2/CO ratios near atmospheric pressures. Reaction kinetics,
      coupled with in situ polarization modulation infrared reflection absorption
      spectroscopy (PM-IRAS) and post-reaction Auger electron spectroscopy (AES)
      measurements, were used to identify the catalytically relevant phases under
      different reaction conditions. Under stoichiometric and reducing conditions at
      all reaction temperatures, as well as net-oxidizing reaction conditions below
      ~475 K, a reduced metallic phase with chemisorbed oxygen is the thermodynamically
      stable and catalytically active phase. On this surface CO oxidation occurs at
      surface defect sites, for example step edges. Only under net-oxidizing reaction
      conditions and above ~475 K is the RuO2 thin film grown on metallic Ru stable and
      active. However, RuO2 is not active itself without the existence of the metal
      substrate, suggesting the importance of a strong metal-substrate interaction
      (SMSI). 

PMID- 22473307
TI  - Gold nanothorns-macroporous silicon hybrid structure: a simple and ultrasensitive
      platform for SERS.
AB  - We synthesised a novel gold-on-porous silicon hybrid material that exhibits a
      highly sensitive and reproducible surface-enhanced Raman spectroscopy (SERS)
      response. The material was fabricated simply by reducing gold chloride with
      hydrofluoric acid on the surface of macro-porous silicon (macro-PSi). The
      material consists of thorn-shaped gold nanocrystals with characteristic shapes
      and sizes on the surface of macro-PSi.

PMID- 22473309
TI  - Two different cationic positions in Cu-SSZ-13?
AB  - H(2)-TPR and FTIR were used to characterize the nature of the Cu ions present in
      the Cu-SSZ-13 zeolite at different ion exchange levels. The results obtained are
      consistent with the presence of Cu ions at two distinct cationic positions in the
      SSZ-13 framework.

PMID- 22473308
TI  - Building a multiple modality, theory-based physical activity intervention: The
      development of CardiACTION!
AB  - OBJECTIVES: Despite the widely acknowledged benefits of regular physical activity
      (PA), specific goals for increased population levels of PA, and strongly
      recommended strategies to promote PA, there is no evidence suggesting that the
      prevalence of PA is improving. If PA intervention research is to be improved,
      theory should be used as the basis for intervention development, participant
      context or environment should be considered in the process, and intervention
      characteristics that will heighten the likelihood of translation into practice
      should be implemented (e.g., ease of implementation, low human resource costs).
      The purpose of this paper is to describe the implementation of the aforementioned
      concepts within the intervention development process associated with CardiACTION
      an ongoing randomized 2 * 2 factorial trial.  METHODS: The Ecological Model of
      Physical Activity integrated with Protection Motivation Theory was used to inform
      the design of the interventions. This integrated model was selected to allow for
      the development of theory-based individual, environmental, and individually +
      environmentally targeted physical activity interventions. All intervention
      strategies were matched to proposed mediators of behavior change. Strategies were
      then matched to the most appropriate interactive technology (i.e., interactive
      computer session, automated telephone counseling, and tailored mailings) delivery
      channel.  CONCLUSIONS: The potential implications of this study include
      determining the independent and combined influence of individual and environment
      mechanisms of behavior change on intervention effectiveness. In addition, all
      intervention models are developed to be scalable and disseminable to a broad
      audience at a low cost.

PMID- 22473310
TI  - Androgenesis: a review through the study of the selfish shellfish Corbicula spp.
AB  - Among the asexual reproductive modes, androgenesis is probably one of the most
      astonishing and least studied mechanisms. In this 'paternal monopolization', the
      maternal nuclear genome fails to participate in zygote development and offspring
      are paternal nuclear clones. Obligate androgenesis is known in only a few
      organisms, including multiple species of clam in the genus Corbicula. Corbicula
      is a good system to review the evolutionary consequences of this 'all-male
      asexuality' because the cytological mechanisms of androgenetic reproduction have
      been described. In Corbicula, sperm are unreduced and, after fertilization, the
      maternal nuclear chromosomes are extruded as two polar bodies. Hermaphroditic
      lineages of Corbicula have a worldwide distribution and seem to reproduce through
      androgenesis, whereas their sexual relatives have restricted ranges. The invasive
      success of these androgenetic Corbicula lineages may be linked to their asexual
      mode of reproduction. We review the phenomenon of androgenesis, focusing on
      evolutionary perspectives, using the genus Corbicula as an exemplar system.

PMID- 22473311
TI  - CD36-deficient congenic strains show improved glucose tolerance and distinct
      shifts in metabolic and transcriptomic profiles.
AB  - Deficiency of fatty acid translocase Cd36 has been shown to have a major role in
      the pathogenesis of metabolic syndrome in the spontaneously hypertensive rat
      (SHR). We have tested the hypothesis that the effects of Cd36 mutation on the
      features of metabolic syndrome are contextually dependent on genomic background.
      We have derived two new congenic strains by introgression of limited chromosome 4
      regions of SHR origin, both including the defective Cd36 gene, into the genetic
      background of a highly inbred model of insulin resistance and dyslipidemia,
      polydactylous (PD) rat strain. We subjected standard diet-fed adult males of PD
      and the congenic PD.SHR4 strains to metabolic, morphometric and transcriptomic
      profiling. We observed significantly improved glucose tolerance and lower fasting
      insulin levels in PD.SHR4 congenics than in PD. One of the PD.SHR4 strains showed
      lower triglyceride concentrations across major lipoprotein fractions combined
      with higher levels of low-density lipoprotein cholesterol compared with the PD
      progenitor. The hepatic transcriptome assessment revealed a network of genes
      differentially expressed between PD and PD.SHR4 with significant enrichment by
      members of the circadian rhythmicity pathway (Arntl (Bmal1), Clock, Nfil3, Per2
      and Per3). In summary, the introduction of the chromosome 4 region of SHR origin
      including defective Cd36 into the PD genetic background resulted in disconnected
      shifts of metabolic profile along with distinct changes in hepatic transcriptome.
      The synthesis of the current results with those obtained in other Cd36-deficient
      strains indicates that the eventual metabolic effect of a deleterious mutation
      such as that of SHR-derived Cd36 is not absolute, but rather a function of
      complex interactions between environmental and genomic background, upon which it
      operates.

PMID- 22473312
TI  - The analysis of purkinje cell dendritic morphology in organotypic slice cultures.
AB  - Purkinje cells are an attractive model system for studying dendritic development,
      because they have an impressive dendritic tree which is strictly oriented in the
      sagittal plane and develops mostly in the postnatal period in small rodents (3).
      Furthermore, several antibodies are available which selectively and intensively
      label Purkinje cells including all processes, with anti-Calbindin D28K being the
      most widely used. For viewing of dendrites in living cells, mice expressing EGFP
      selectively in Purkinje cells (11) are available through Jackson labs.
      Organotypic cerebellar slice cultures cells allow easy experimental manipulation
      of Purkinje cell dendritic development because most of the dendritic expansion of
      the Purkinje cell dendritic tree is actually taking place during the culture
      period (4). We present here a short, reliable and easy protocol for viewing and
      analyzing the dendritic morphology of Purkinje cells grown in organotypic
      cerebellar slice cultures. For many purposes, a quantitative evaluation of the
      Purkinje cell dendritic tree is desirable. We focus here on two parameters,
      dendritic tree size and branch point numbers, which can be rapidly and easily
      determined from anti-calbindin stained cerebellar slice cultures. These two
      parameters yield a reliable and sensitive measure of changes of the Purkinje cell
      dendritic tree. Using the example of treatments with the protein kinase C (PKC)
      activator PMA and the metabotropic glutamate receptor 1 (mGluR1) we demonstrate
      how differences in the dendritic development are visualized and quantitatively
      assessed. The combination of the presence of an extensive dendritic tree,
      selective and intense immunostaining methods, organotypic slice cultures which
      cover the period of dendritic growth and a mouse model with Purkinje cell
      specific EGFP expression make Purkinje cells a powerful model system for
      revealing the mechanisms of dendritic development.

PMID- 22473314
TI  - Cancer stem cell vaccination confers significant antitumor immunity.
AB  - Most studies of cancer stem cells (CSC) involve the inoculation of cells from
      human tumors into immunosuppressed mice, preventing an assessment on the
      immunologic interactions and effects of CSCs. In this study, we examined the
      vaccination effects produced by CSC-enriched populations from histologically
      distinct murine tumors after their inoculation into different syngeneic
      immunocompetent hosts. Enriched CSCs were immunogenic and more effective as an
      antigen source than unselected tumor cells in inducing protective antitumor
      immunity. Immune sera from CSC-vaccinated hosts contained high levels of IgG
      which bound to CSCs, resulting in CSC lysis in the presence of complement. CTLs
      generated from peripheral blood mononuclear cells or splenocytes harvested from
      CSC-vaccinated hosts were capable of killing CSCs in vitro. Mechanistic
      investigations established that CSC-primed antibodies and T cells were capable of
      selective targeting CSCs and conferring antitumor immunity. Together, these proof
      of-concept results provide a rationale for a new type of cancer immunotherapy
      based on the development of CSC vaccines that can specifically target CSCs.

PMID- 22473315
TI  - Lactate-induced IL-8 pathway in endothelial cells--letter.
AB  - Vegran and colleagues proposed a model in which the lactate released from tumor
      cells through MCT4 would be taken up by endothelial cells via the MCT1
      transporter and stimulate angiogenesis, using human umbilical vein endothelial
      cells (HUVECs) as model of tumor endothelial cells. By analyzing a total of 505
      cases of human tumor samples immunostained for MCT1, we do not confirm plasma
      membrane expression of MCT1 in the endothelial cells of tumor-associated vessels.

PMID- 22473317
TI  - Adherence to antidepressant treatment: what the doctor thinks and what the
      patient says.
AB  - Adherence to antidepressant treatment has been shown to range from 30 to 70%. The
      aim of this study was to compare the patient's self-report of adherence with the
      doctors' estimation of adherence and therapeutic alliance in 104 outpatients with
      mood and/or anxiety disorder treated with antidepressants. The adherence scores
      estimated by the patients and the doctors were significantly different, the
      doctors underestimating adherence in 29% of cases and overestimating it in 31% of
      cases compared to the patients' evaluation. Adherence measured by drug plasma
      concentration, despite being higher than expected from previously published
      reports, was in line with the patients' self-reported score but not the doctors'
      estimation. Finally, the patients' and the doctors' Helping Alliance scores were
      not related to adherence self-report.

PMID- 22473318
TI  - In vitro culture and characterization of alveolar bone osteoblasts isolated from
      type 2 diabetics.
AB  - In order to understand the mechanisms of poor osseointegration following dental
      implants in type 2 diabetics, it is important to study the biological properties
      of alveolar bone osteoblasts isolated from these patients. We collected alveolar
      bone chips under aseptic conditions and cultured them in vitro using the tissue
      explants adherent method. The biological properties of these cells were
      characterized using the following methods: alkaline phosphatase (ALP) chemical
      staining for cell viability, Alizarin red staining for osteogenic
      characteristics, MTT test for cell proliferation, enzyme dynamics for ALP
      contents, radio-immunoassay for bone gla protein (BGP) concentration, and ELISA
      for the concentration of type I collagen (COL-I) in the supernatant. Furthermore,
      we detected the adhesion ability of two types of cells from titanium slices using
      non-specific immunofluorescence staining and cell count. The two cell forms
      showed no significant difference in morphology under the same culture conditions.
      However, the alveolar bone osteoblasts received from type 2 diabetic patients had
      slower growth, lower cell activity and calcium nodule formation than the normal
      ones. The concentration of ALP, BGP and COL-I was lower in the supernatant of
      alveolar bone osteoblasts received from type 2 diabetic patients than in that
      received from normal subjects (P < 0.05). The alveolar bone osteoblasts obtained
      from type 2 diabetic patients can be successfully cultured in vitro with the same
      morphology and biological characteristics as those from normal patients, but with
      slower growth and lower concentration of specific secretion and lower combining
      ability with titanium than normal ones.

PMID- 22473319
TI  - Influence of cueing on the preparation and execution of untrained and trained
      complex motor responses.
AB  - This study investigated the influence of cueing on the performance of untrained
      and trained complex motor responses. Healthy adults responded to a visual target
      by performing four sequential movements (complex response) or a single movement
      (simple response) of their middle finger. A visual cue preceded the target by an
      interval of 300, 1000, or 2000 ms. In Experiment 1, the complex and simple
      responses were not previously trained. During the testing session, the complex
      response pattern varied on a trial-by-trial basis following the indication
      provided by the visual cue. In Experiment 2, the complex response and the simple
      response were extensively trained beforehand. During the testing session, the
      trained complex response pattern was performed in all trials. The latency of the
      untrained and trained complex responses decreased from the short to the medium
      and long cue-target intervals. The latency of the complex response was longer
      than that of the simple response, except in the case of the trained responses and
      the long cue-target interval. These results suggest that the preparation of
      untrained complex responses cannot be completed in advance, this being possible,
      however, for trained complex responses when enough time is available. The
      duration of the 1st submovement, 1st pause and 2nd submovement of the untrained
      and the trained complex responses increased from the short to the long cue-target
      interval, suggesting that there is an increase of online programming of the
      response possibly related to the degree of certainty about the moment of target
      appearance.

PMID- 22473320
TI  - Participation of the GABAergic system in the anesthetic effect of Lippia alba
      (Mill.) N.E. Brown essential oil.
AB  - The objective of this study was to identify the possible involvement of the
      GABAergic system in the anesthetic effect of Lippia alba essential oil (EO). We
      propose a new animal model using silver catfish (Rhamdia quelen) exposed to an
      anesthetic bath to study the mechanism of action of EO. To observe the induction
      and potentiation of the anesthetic effect of EO, juvenile silver catfish (9.30 +/
      1.85 g; 10.15 +/- 0.95 cm; N = 6) were exposed to various concentrations of L.
      alba EO in the presence or absence of diazepam [an agonist of high-affinity
      binding sites for benzodiazepinic (BDZ) sites coupled to the GABA A receptor
      complex]. In another experiment, fish (N = 6) were initially anesthetized with
      the EO and then transferred to an anesthetic-free aquarium containing flumazenil
      (a selective antagonist of binding sites for BDZ coupled to the GABA A receptor
      complex) or water to assess recovery time from the anesthesia. In this case,
      flumazenil was used to observe the involvement of the GABA-BDZ receptor in the EO
      mechanism of action. The results showed that diazepam potentiates the anesthetic
      effect of EO at all concentrations tested. Fish exposed to diazepam and EO showed
      faster recovery from anesthesia when flumazenil was added to the recovery bath
      (12.0 +/- 0.3 and 7.2 +/- 0.7, respectively) than those exposed to water (9.2 +/-
      0.2 and 3.5 +/- 0.3, respectively). In conclusion, the results demonstrated the
      involvement of the GABAergic system in the anesthetic effect of L. alba EO on
      silver catfish.

PMID- 22473321
TI  - Electron paramagnetic resonance study of lipid and protein membrane components of
      erythrocytes oxidized with hydrogen peroxide.
AB  - Electron paramagnetic resonance (EPR) spectroscopy of spin labels was used to
      monitor membrane dynamic changes in erythrocytes subjected to oxidative stress
      with hydrogen peroxide (H(2)O(2)). The lipid spin label, 5-doxyl stearic acid,
      responded to dramatic reductions in membrane fluidity, which was correlated with
      increases in the protein content of the membrane. Membrane rigidity, associated
      with the binding of hemoglobin (Hb) to the erythrocyte membrane, was also
      indicated by a spin-labeled maleimide, 5-MSL, covalently bound to the sulfhydryl
      groups of membrane proteins. At 2% hematocrit, these alterations in membrane
      occurred at very low concentrations of H(2)O(2) (50 uM) after only 5 min of
      incubation at 37 degrees C in azide phosphate buffer, pH 7.4. Lipid peroxidation,
      suggested by oxidative hemolysis and malondialdehyde formation, started at 300 uM
      H(2)O(2) (for incubation of 3 h), which is a concentration about six times higher
      than those detected with the probes. Ascorbic acid and alpha-tocopherol protected
      the membrane against lipoperoxidation, but did not prevent the binding of
      proteins to the erythrocyte membrane. Moreover, the antioxidant (+)-catechin,
      which also failed to prevent the cross-linking of cytoskeletal proteins with Hb,
      was very effective in protecting erythrocyte ghosts from lipid peroxidation
      induced by the Fenton reaction. This study also showed that EPR spectroscopy can
      be useful to assess the molecular dynamics of red blood cell membranes in both
      the lipid and protein domains and examine oxidation processes in a system that is
      so vulnerable to oxidation.

PMID- 22473322
TI  - Experimental model of heterotopic ossification in Wistar rats.
AB  - Heterotopic ossification (HO) is a metaplastic biological process in which there
      is newly formed bone in soft tissues adjacent to large joints, resulting in joint
      mobility deficit. In order to determine which treatment techniques are more
      appropriate for such condition, experimental models of induced heterotopic bone
      formation have been proposed using heterologous demineralized bone matrix
      implants and bone morphogenetic protein and other tissues. The objective of the
      present experimental study was to identify a reliable protocol to induce HO in
      Wistar rats, based on autologous bone marrow (BM) implantation, comparing 3
      different BM volumes and based on literature evidence of this HO induction model
      in larger laboratory animals. Twelve male Wistar albino rats weighing 350/390 g
      were used. The animals were anesthetized for blood sampling before HO induction
      in order to quantify serum alkaline phosphatase (ALP). HO was induced by BM
      implantation in both quadriceps muscles of these animals, experimental group
      (EG). Thirty-five days after the induction, another blood sample was collected
      for ALP determination. The results showed a weight gain in the EG and no
      significant difference in ALP levels when comparing the periods before and after
      induction. Qualitative histological analysis confirmed the occurrence of
      heterotopic ossification in all 12 EG rats. In conclusion, the HO induction model
      was effective when 0.35 mL autologous BM was applied to the quadriceps of Wistar
      rats.

PMID- 22473323
TI  - Heparan sulphate, its derivatives and analogues share structural characteristics
      that can be exploited, particularly in inhibiting microbial attachment.
AB  - Heparan sulphate (HS) and the related polysaccharide, heparin, exhibit
      conformational and charge arrangement properties, which provide a degree of
      redundancy allowing several seemingly distinct sequences to exhibit the same
      activity. This can also be mimicked by other sulphated polysaccharides, both in
      overall effect and in the details of interactions and structural consequences of
      interactions with proteins. Together, these provide a source of active compounds
      suitable for further development as potential drugs. These polysaccharides also
      possess considerable size, which bestows upon them an additional useful property:
      the capability of disrupting processes comprising many individual interactions,
      such as those characterising the attachment of microbial pathogens to host cells.
      The range of involvement of HS in microbial attachment is reviewed and examples,
      which include viral, bacterial and parasitic infections and which, in many cases,
      are now being investigated as potential targets for intervention, are identified.

PMID- 22473324
TI  - Three-dimensional kinematic analysis of upper and lower limb motion during gait
      of post-stroke patients.
AB  - The aim of this study was to analyze the alterations of arm and leg movements of
      patients during stroke gait. Joint angles of upper and lower limbs and
      spatiotemporal variables were evaluated in two groups: hemiparetic group (HG, 14
      hemiparetic men, 53 +/- 10 years) and control group (CG, 7 able-bodied men, 50 +/
      4 years). The statistical analysis was based on the following comparisons (P <=
      0.05): 1) right versus left sides of CG; 2) affected (AF) versus unaffected (UF)
      sides of HG; 3) CG versus both the affected and unaffected sides of HG, and 4) an
      intracycle comparison of the kinematic continuous angular variables between HG
      and CG. This study showed that the affected upper limb motion in stroke gait was
      characterized by a decreased range of motion of the glenohumeral (HG: 6.3 +/-
      4.5, CG: 20.1 +/- 8.2) and elbow joints (AF: 8.4 +/- 4.4, UF: 15.6 +/- 7.6) on
      the sagittal plane and elbow joint flexion throughout the cycle (AF: 68.2 +/-
      0.4, CG: 46.8 +/- 2.7). The glenohumeral joint presented a higher abduction angle
      (AF: 14.2 +/- 1.6, CG: 11.5 +/- 4.0) and a lower external rotation throughout the
      cycle (AF: 4.6 +/- 1.2, CG: 22.0 +/- 3.0). The lower limbs showed typical
      alterations of the stroke gait patterns. Thus, the changes in upper and lower
      limb motion of stroke gait were identified. The description of upper limb motion
      in stroke gait is new and complements gait analysis.

PMID- 22473325
TI  - An application of a new evidence grading system to research on the chronic care
      model.
AB  - Methodological quality undergirds all evidence-based medicine because without
      strong evidence supporting or refuting the efficacy of an intervention, the
      movement toward basing medical decisions and practice on scientific evidence is
      not sustainable. Recently, the consensus that had existed regarding the hierarchy
      of evidence produced by a study design was challenged on the basis that existing
      guidelines failed to properly define key terms, weight the merits of certain non
      randomized controlled trials, and employ a comprehensive list of study design
      limitations to render evaluative conclusions, to name a few of the challenges.
      The present study introduces a new grading system that overcomes, or at the very
      least greatly diminishes, these challenges. This new method is applied to the
      literature on the Chronic Care Model and the results are then compared to several
      of the most popular grading guidelines currently in use. These results revealed
      substantial differences between the guidelines in accordance with previous
      research that challenged existing methods. Furthermore, the present study lends
      support to the proposed grading guideline although further research into its
      validity and reliability is needed.

PMID- 22473326
TI  - Dissection and culture of mouse dopaminergic and striatal explants in three
      dimensional collagen matrix assays.
AB  - Midbrain dopamine (mdDA) neurons project via the medial forebrain bundle towards
      several areas in the telencephalon, including the striatum(1). Reciprocally,
      medium spiny neurons in the striatum that give rise to the striatonigral (direct)
      pathway innervate the substantia nigra(2). The development of these axon tracts
      is dependent upon the combinatorial actions of a plethora of axon growth and
      guidance cues including molecules that are released by neurites or by
      (intermediate) target regions(3,4). These soluble factors can be studied in vitro
      by culturing mdDA and/or striatal explants in a collagen matrix which provides a
      three-dimensional substrate for the axons mimicking the extracellular
      environment. In addition, the collagen matrix allows for the formation of
      relatively stable gradients of proteins released by other explants or cells
      placed in the vicinity (e.g. see references 5 and 6). Here we describe methods
      for the purification of rat tail collagen, microdissection of dopaminergic and
      striatal explants, their culture in collagen gels and subsequent
      immunohistochemical and quantitative analysis. First, the brains of E14.5 mouse
      embryos are isolated and dopaminergic and striatal explants are microdissected.
      These explants are then (co)cultured in collagen gels on coverslips for 48 to 72
      hours in vitro. Subsequently, axonal projections are visualized using neuronal
      markers (e.g. tyrosine hydroxylase, DARPP32, or betaIII tubulin) and axon growth
      and attractive or repulsive axon responses are quantified. This neuronal
      preparation is a useful tool for in vitro studies of the cellular and molecular
      mechanisms of mesostriatal and striatonigral axon growth and guidance during
      development. Using this assay, it is also possible to assess other (intermediate)
      targets for dopaminergic and striatal axons or to test specific molecular cues.

PMID- 22473327
TI  - Diastereoselective alkylation reactions of 1-methylcyclohexa-2,5-diene-1
      carboxylic acid.
AB  - The deprotonation and alkylation of 1-methylcyclohexa-2,5-diene-1-carboxylic acid
      has been investigated under a range of conditions. In all cases, the formation of
      compounds 14 was found to be completely stereoselective, although compound 14c
      was formed as an impurity when alkyl iodides were used as electrophiles, and
      doubly-alkylated compounds 17 were formed in some cases when alkyl bromides were
      used.

PMID- 22473328
TI  - Carcinogenic metals and the epigenome: understanding the effect of nickel,
      arsenic, and chromium.
AB  - Carcinogenic metals, such as nickel, arsenic, and chromium, are widespread
      environmental and occupational pollutants. Chronic exposure to these metals has
      been connected with increased risks of numerous cancers and as well as non
      carcinogenic health outcomes, including cardiovascular disease, neurologic
      deficits, neuro-developmental deficits in childhood, and hypertension. However,
      currently the specific molecular targets for metal toxicity and carcinogenicity
      are not fully understood. Here, we propose that the iron- and 2-oxoglutarate
      dependent dioxygenase family enzymes, as well as, other histone modifying enzymes
      are important intracellular targets that mediate the toxicity and carcinogenicity
      of nickel, and maybe potential targets in chromium and arsenic induced
      carcinogenesis. Our data demonstrate that all three metals are capable of
      inducing post-translational histone modifications and affecting the enzymes that
      modulate them (i.e. the iron- and 2-oxoglutarate-dependent dioxygenase family,
      including HIF-prolyl hydroxylase PHD2, histone demethylase JHDM2A/JMJD1A, and DNA
      repair enzymes ABH3 and ABH2, and histone methyltransferases, G9a). Given the
      effects that these metals can exert on the epigenome, future studies of their
      involvement in histone modifying enzymes dynamics would deepen our understanding
      on their respective toxicities and carcinogenicities.

PMID- 22473329
TI  - Anti-obesity effects of the combined administration of CB1 receptor antagonist
      rimonabant and melanin-concentrating hormone antagonist SNAP-94847 in diet
      induced obese mice.
AB  - OBJECTIVE: Current anti-obesity monotherapies have proven only marginally
      effective and are often accompanied by adverse side effects. The cannabinoid 1
      (CB1) receptor antagonist rimonabant, while effective at producing weight loss,
      has been discontinued from clinical use owing to increased incidence of
      depression. This study investigates the interaction between the cannabinoid and
      melanin-concentrating hormone (MCH) systems in food intake, body weight control,
      and mood. DESIGN: Lean male C57BL/6 mice were injected i.p. with rimonabant (0.0,
      0.03, 0.3 and 3.0 mg kg(-1)) or the MCH1-R antagonist SNAP-94847 (0.0, 1.0, 5.0
      and 10.0 mg kg(-1)) to establish dose response parameters for each drug. Diet
      induced obese (DIO) mice were given either vehicle, sub-threshold dose of
      rimonabant and SNAP-94847 alone or in combination. Impact on behavioral outcomes,
      food intake, body weight, plasma metabolites and expression of key metabolic
      proteins in the brown adipose tissue (BAT) and white adipose tissue (WAT) were
      measured. RESULTS: The high doses of rimonabant and SNAP-94847 produced a
      reduction in food intake after 2 and 24 h. Combining sub-threshold doses of
      rimonabant and SNAP-94847 produced a significantly greater loss of body weight in
      DIO mice compared with vehicle and monotherapies. In addition, combining sub
      effective doses of these drugs led to a shift in markers of thermogenesis in BAT
      and lipid metabolism in WAT consistent with increased energy expenditure and
      lipolysis. Furthermore, co-administration of rimonabant and SNAP-94847 produced a
      transient reduction in food intake, and significantly reduced fat mass and
      adipocyte size. Importantly, SNAP-94847 significantly attenuated the ability of
      rimonabant to reduced immobility time in the forced swim test. CONCLUSION: These
      results provide proof of principle that combination of rimonabant and a MCH1
      receptor antagonist is highly effective in reducing body weight below that
      achieved by rimonabant and SNAP-94847 monotherapies. In addition, the combination
      therapy normalizes the rimonabant-induced behavioral changes seen in the forced
      swim test.

PMID- 22473331
TI  - Bone: Growth hormone replacement--implications for bone health.

PMID- 22473330
TI  - Arterial calcification and bone physiology: role of the bone-vascular axis.
AB  - Bone never forms without vascular interactions. This simple statement of fact
      does not adequately reflect the physiological and pharmacological implications of
      the relationship. The vasculature is the conduit for nutrient exchange between
      bone and the rest of the body. The vasculature provides the sustentacular niche
      for development of osteoblast progenitors and is the conduit for egress of bone
      marrow cell products arising, in turn, from the osteoblast-dependent
      haematopoietic niche. Importantly, the second most calcified structure in humans
      after the skeleton is the vasculature. Once considered a passive process of dead
      and dying cells, vascular calcification has emerged as an actively regulated form
      of tissue biomineralization. Skeletal morphogens and osteochondrogenic
      transcription factors are expressed by cells within the vessel wall, which
      regulates the deposition of vascular calcium. Osteotropic hormones, including
      parathyroid hormone, regulate both vascular and skeletal mineralization.
      Cellular, endocrine and metabolic signals that flow bidirectionally between the
      vasculature and bone are necessary for both bone health and vascular health.
      Dysmetabolic states including diabetes mellitus, uraemia and hyperlipidaemia
      perturb the bone-vascular axis, giving rise to devastating vascular and skeletal
      disease. A detailed understanding of bone-vascular interactions is necessary to
      address the unmet clinical needs of an increasingly aged and dysmetabolic
      population.

PMID- 22473332
TI  - The changing epidemiology of iodine deficiency.
AB  - Globally, about 2 thousand million people are affected by iodine deficiency.
      Although endemic goitre is the most visible sign of iodine deficiency, its most
      devastating consequence is brain damage causing mental retardation in children.
      The relationship between iodine deficiency and brain damage was not clearly
      established until the 1980s when the term iodine deficiency disorders (IDDs),
      which encompass a spectrum of conditions caused by iodine deficiency, was
      introduced. This paradigm shift in the understanding of the clinical consequences
      of iodine deficiency led to a change in iodine deficiency assessment. The median
      urinary iodine excretion level has been recommended as the preferred indicator
      for monitoring population iodine deficiency status since 2001. The 2007 WHO
      urinary iodine data in schoolchildren from 130 countries revealed that iodine
      intake is still insufficient in 47 countries. Furthermore, about one-third of
      countries lack national estimates of the prevalence of iodine deficiency. The
      picture that has emerged from available data worldwide over the past two decades
      is that IDDs are not confined to remote, mountainous areas in developing
      countries, but are a global public health problem that affects most countries,
      including developed countries and island nations. The recognition of the
      universality of iodine deficiency highlights the need to develop and apply new
      strategies to establish and maintain sustainable IDD elimination and strengthen
      regular monitoring programmes.

PMID- 22473334
TI  - Bone: Gut immune status affects bone mass in mice.

PMID- 22473333
TI  - Muscles, exercise and obesity: skeletal muscle as a secretory organ.
AB  - During the past decade, skeletal muscle has been identified as a secretory organ.
      Accordingly, we have suggested that cytokines and other peptides that are
      produced, expressed and released by muscle fibres and exert either autocrine,
      paracrine or endocrine effects should be classified as myokines. The finding that
      the muscle secretome consists of several hundred secreted peptides provides a
      conceptual basis and a whole new paradigm for understanding how muscles
      communicate with other organs, such as adipose tissue, liver, pancreas, bones and
      brain. However, some myokines exert their effects within the muscle itself. Thus,
      myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis,
      whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also
      appears to have systemic effects on the liver, adipose tissue and the immune
      system, and mediates crosstalk between intestinal L cells and pancreatic islets.
      Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which
      improves the endothelial function of the vascular system; and the PGC-1alpha
      dependent myokine irisin, which drives brown-fat-like development. Studies in the
      past few years suggest the existence of yet unidentified factors, secreted from
      muscle cells, which may influence cancer cell growth and pancreas function. Many
      proteins produced by skeletal muscle are dependent upon contraction; therefore,
      physical inactivity probably leads to an altered myokine response, which could
      provide a potential mechanism for the association between sedentary behaviour and
      many chronic diseases.

PMID- 22473335
TI  - Advances in the follow-up of differentiated or medullary thyroid cancer.
AB  - The long-term survival of patients with thyroid cancer and the possibility of
      tumour recurrence up to 30-40 years after the achievement of a disease-free
      status illustrate the importance of lifelong follow-up in these individuals. This
      Review discusses the most innovative aspects of follow-up protocols for patients
      with differentiated thyroid cancer, that is, of papillary or follicular
      hystotype, and those with medullary thyroid cancer. Particular focus is placed on
      the relevance of new ultrasensitive assays for thyroglobulin measurement and the
      option of using recombinant human TSH to stimulate thyroglobulin secretion.
      Methods to compensate for the loss of diagnostic significance of serum
      thyroglobulin levels in patients with differentiated thyroid cancer and
      circulating anti-thyroglobulin antibodies are highlighted, as well as the role of
      the postoperative calcitonin stimulation test and the clinical relevance of
      determining the doubling time of calcitonin and carcinoembryonic antigen in
      patients with medullary thyroid cancer. Moreover, this Review gives some insights
      into the role of molecular thyroid cancer testing, both for prognostic and for
      therapeutic purposes. Finally, a general overview of traditional imaging
      procedures, such as neck ultrasonography, CT, MRI and bone scintigraphy, is
      provided alongside a comparison with new nuclear imaging tests such as PET.

PMID- 22473336
TI  - Reproductive endocrinology: Mass spectrometry 'gold standard' for measuring
      steroid sex hormones?

PMID- 22473337
TI  - Intracranial stenosis in young patients: unique characteristics and risk factors.
AB  - BACKGROUND: Intracranial stenosis in young patients appears to have different
      characteristics from that observed in the older population. OBJECTIVE: To study
      the differences in the pathogenesis of intracranial stenosis in younger patients
      as compared to the older population. METHODS: The clinical characteristics of
      patients with angiographically confirmed intracranial stenosis were matched to a
      healthy population using the National Health and Nutrition Examination Study
      (NHANES). The study population was stratified into two age groups (<=45 and >45
      years). The relative risk (odds ratios) and attributable risk of known
      cardiovascular risk factors were estimated. RESULTS: A total of 17 (11%) patients
      from 153 patients with intracranial stenosis were aged <=45 years. These patients
      were more likely to be women (53 vs. 28%, p < 0.05). The location of the lesion
      in the young patients was more likely to be in the internal carotid artery (65
      vs. 29%, p < 0.05). When compared with the stroke risk factors from the NHANES
      control population, the attributable risk of hypertension, diabetes mellitus, and
      coronary artery disease for intracranial stenosis was lower among patients aged
      <=45 years than that for patients aged >45 years (6.4 vs. 13.1%, 19.9 vs. 33.0%
      and 1.0 vs. 10.8%, respectively). Hyperlipidemia had a greater attributable risk
      of intracranial stenosis in patients <=45 than in those >45 years of age (23.3
      vs. 9.3%). CONCLUSIONS: Intracranial stenosis in young patients is predominantly
      located in the anterior circulation and more frequently occurs in young women.
      Even though the stroke risk factors appear to be strongly associated with
      intracranial stenosis in this age group, the impact of these risk factors is low
      due to the low prevalence.

PMID- 22473338
TI  - Phox2b expression in the taste centers of fish.
AB  - The homeodomain transcription factor Phox2b controls the formation of the sensory
      motor reflex circuits of the viscera in vertebrates. Among Phox2b-dependent
      structures characterized in rodents is the nucleus of the solitary tract, the
      first relay for visceral sensory input, including taste. Here we show that Phox2b
      is expressed throughout the primary taste centers of two cyprinid fish, Danio
      rerio and Carassius auratus, i.e., in their vagal, glossopharyngeal, and facial
      lobes, providing the first molecular evidence for their homology with the nucleus
      of the solitary tract of mammals and suggesting that a single ancestral Phox2b
      positive neuronal type evolved to give rise to both fish and mammalian
      structures. In zebrafish larvae, the distribution of Phox2b2+ neurons, combined
      with the expression pattern of Olig4 (a homologue of Olig3, determinant of the
      nucleus of the solitary tract in mice), reveals that the superficial position and
      sheet-like architecture of the viscerosensory column in cyprinid fish, ideally
      suited for the somatotopic representation of oropharyngeal and bodily surfaces,
      arise by radial migration from a dorsal progenitor domain, in contrast to the
      tangential migration observed in amniotes.

PMID- 22473339
TI  - Low dosed interferon alpha augments the anti-tumor potential of histone
      deacetylase inhibition on prostate cancer cell growth and invasion.
AB  - We evaluated whether low-dosed interferon alpha (IFNa) may augment the anti-tumor
      potential of the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on
      prostate cancer cells in vitro and in vivo. PC-3, DU-145, or LNCaP prostate
      cancer cells were treated with VPA (1 mM), IFNa (200 U/ml), or with the VPA-IFNa
      combination. Tumor cell growth, cell cycle progression, and cell cycle regulating
      proteins were then investigated by the MTT assay, flow cytometry, and western
      blotting. Tumor cell adhesion to endothelium or to immobilized extracellular
      matrix proteins, as well as migratory properties of the cells, were evaluated.
      Integrin alpha and beta adhesion molecules and alterations of cell signaling
      pathways were analyzed. Finally, effects of the drug treatment on prostate cancer
      growth in vivo were determined in the NOD/SCID mouse model. VPA reduced tumor
      cell adhesion, migration, and growth in vitro. A much stronger anti-cancer
      potential was evoked by the VPA-IFNa combination, although IFNa in itself did not
      block growth or adhesion. The same effect was seen when tumor growth was
      evaluated in vivo. Molecular analysis revealed distinct elevation of histone H3
      acetylation caused by VPA which was further up-regulated by VPA-IFNa, whereas
      IFNa alone did not alter H3 acetylation. The combinatorial benefit became obvious
      in Akt phosphorylation, p21 and p27 and integrin alpha1, alpha3, and beta1
      expression. Application of low-dosed IFNa to a VPA based regimen profoundly
      boosts the anti-tumor properties of VPA. The combined use of VPA and low-dosed
      IFNa may therefore be an innovative option in treating advanced prostate cancer.

PMID- 22473340
TI  - Spasmolytic and antinociceptive activities of ursolic acid and acacetin
      identified in Agastache mexicana.
AB  - Agastache mexicana is a plant in high demand that has long been used in Mexican
      folk medicine to treat anxiety, insomnia, and stomachache, among other
      afflictions. Ursolic acid and acacetin were isolated and identified as two
      possible active compounds of A. mexicana aerial parts. An antinociceptive
      response was demonstrated in a significant and dose-dependent manner with ursolic
      acid and acacetin (i. p. and p. o.) in comparison to the analgesic diclofenac by
      using the writhing test in mice. Moreover, acacetin also produced a significant
      concentration-dependent spasmolytic response with major efficacy compared to
      ursolic acid and papaverine by using rings from the isolated guinea pig ileum.
      These results provide evidence of the presence of two active constituents of
      Agastache mexicana reinforcing its utility as a therapy for visceral pain as used
      in traditional medicine.

PMID- 22473341
TI  - The dilemma of researchers, the insensibility of policy-makers and the distress
      of Brazilian dentistry journals.

PMID- 22473342
TI  - Children's discomfort in assessments using different methods for approximal
      caries detection.
AB  - Because discomfort caused by different approximal caries detection methods can
      influence their performance, the assessment of this discomfort is important.
      Thus, this study aimed to evaluate the discomfort reported by children after the
      use of different diagnostic methods to detect approximal caries lesions in
      primary teeth: visual inspection, bitewing radiography, laser fluorescence
      (DIAGNOdent pen - LFpen) and temporary separation with orthodontic rubbers.
      Seventy-six children aged 4 to 12 years were examined using these methods. Their
      discomfort was assessed using the Wong-Baker scale and compared among the
      methods. Visual inspection caused less discomfort than did other methods.
      Radiography and the LFpen presented similar levels of discomfort. Older children
      reported higher discomfort using temporary separation, whereas younger children
      reported less discomfort with the LFpen. In conclusion, radiographic, temporary
      separation and LFpen methods provoke higher discomfort than visual inspection.

PMID- 22473343
TI  - Calcium binding to S. mutans grown in the presence or absence of sucrose.
AB  - Sucrose is the most cariogenic dietary carbohydrate because it is a substrate for
      insoluble extracellular polysaccharide (IEPS) production in dental biofilms,
      which can proportionally decrease bacterial density and, consequently, the number
      of biofilm calcium (Ca) binding sites. Ca bound to bacterial cell walls can be
      released into the biofilm fluid during a cariogenic challenge, reducing the
      driving force for mineral dissolution provoked by the pH drop. Thus, we
      investigated the effect of an IEPS-rich extracellular matrix on bacterial Ca
      binding after treatment with Ca solutions. Streptococcus mutans Ingbritt 1600 was
      cultivated in culture broths supplemented with 1.0% sucrose or 0.5% glucose +
      0.5% fructose. The IEPS concentration in bacterial pellets was determined after
      alkaline extraction. Bacterial pellets were treated with 1 mM or 10 mM Ca++
      solutions at 37oC for 10 to 60 min. Ca binding to bacterial pellets, determined
      after acid extraction using the Arsenazo III reagent, was fast and concentration
      dependent. Although the IEPS concentration was approximately ten times higher in
      bacterial pellets cultivated in sucrose as compared to its monossaccharides,
      bound Ca concentration after Ca treatment was similar in both conditions. These
      results suggest that IEPS may not influence the amount of Ca bound to reservoirs
      of dental biofilms.

PMID- 22473344
TI  - Influence of pulp condition on the accuracy of an electronic foramen locator in
      posterior teeth: an in vivo study.
AB  - The aim of this study was to assess, in vivo, the accuracy of the NovApex(r)
      electronic foramen locator in determining working length (WL) in vital and
      necrotic posterior teeth. The NovApex(r)was used in 144 canals: 35 teeth with
      vital pulps (68 canals) and 42 teeth with necrotic pulps (76 canals). WL was
      measured with the NovApex(r) locator and confirmed using the radiographic method.
      Differences between electronic and radiographic measurements ranging between 0.0
      and 0.4 millimeters were classified as acceptable; differences equal to or
      greater than 0.5 millimeter were considered unacceptable. Pearson's chi-square
      test was used to assess the influence of pulp condition on the accuracy of
      NovApex(r)(a = 0.05). Regardless of pulp condition, differences between
      electronic and radiographic WL measurements were acceptable in 73.61% of the
      canals. No statistically significant differences in accuracy were observed when
      comparing vital and necrotic canals (p > 0.05). There were 38 unacceptable
      measurements. In none of these cases was the file tip located beyond the
      radiographic apex; in 32, it was located short of the NovApex(r) measurement.
      Pulp condition had no significant effect on the accuracy of NovApex(r).

PMID- 22473345
TI  - Agreement between adolescents' and their mothers' reports of oral health-related
      quality of life.
AB  - The aim of this study was to determine the level of agreement between reports by
      adolescents and their mothers regarding the impact of oral health on the
      adolescents' quality of life. The sample consisted of 960 pairs of adolescents
      aged 11 to 14 years and their mothers. The Brazilian version of the Parental
      Caregiver Perceptions Questionnaire (P-CPQ) and the short form of the Child
      Perceptions Questionnaire (CPQ11-14) were administered. Agreement on the total
      scale and the subscales was determined through a comparison of mean values. The
      means of the directional and absolute differences were also determined. Agreement
      on each item on the group level and in the individual pairs was analyzed using
      the Intraclass Correlation Coefficient (ICC). The difference between the means
      and the directional differences were significant for the total score as well as
      for the functional limitation and social well-being subscales (p < 0.001). The
      ICC for the total P-CPQ and CPQ11-14 scores was 0.43. The ICC indicated weak
      agreement on the subscales, ranging from 0.36 to 0.40. Agreement between reports
      by adolescents and their mothers regarding oral health-related quality of life
      (OHRQoL) was moderate, indicating that both perspectives should be considered.

PMID- 22473346
TI  - Risk factors associated with facial fractures.
AB  - The aim of the present study was to identify risk factors for facial fractures in
      patients treated in the emergency department of a hospital. The medical charts of
      1121 patients treated in an emergency ward over a three-year period were
      analyzed. The independent variables were gender, age, place of residence (urban
      or rural area) and type of accident. The dependent variables were fractured
      mandible, zygoma, maxilla, nasal bone and more than one fractured facial bone.
      Statistical analysis was performed using the chi-square test (a < 0.05),
      univariate and multivariate Poisson distributions and the logistic regression
      analysis (p < 0.20). Maxillofacial trauma was recorded in 790 charts (70.5%),
      with 393 (35.1%) charts reporting facial fractures. Motorcycle accidents were
      found to be the main risk factor for mandibular fractures (PR = 1.576, CI = 1.402
      1.772) and simultaneous fractures of more than one facial bone (OR = 4.625, CI =
      1.888-11.329) as well as the only risk factor for maxillary bone fractures (OR =
      11.032, CI = 5.294-22.989). Fractures of the zygomatic and nasal bones were
      mainly associated with accidents involving animals (PR = 1.206, CI = 1.104-1.317)
      and sports (OR = 8.710, CI = 4.006-18.936), respectively. The determinant for the
      majority of facial fractures was motorcycle accidents, followed by accidents
      involving animals and sports.

PMID- 22473347
TI  - The antimicrobial effect of 0.1 ppm ozonated water on 24-hour plaque
      microorganisms in situ.
AB  - Ozone is a known oxidant present in the atmosphere and is commercially produced
      by simple ozonizer machines. It is a powerful antimicrobial agent in its gaseous
      and aqueous forms. Ozone readily dissolves in water and retains its antimicrobial
      property even in the dissolved state. In this study, the effect of 0.1 ppm
      ozonated water was analyzed on 24-hour supragingival plaque (SP) samples in situ.
      SP was collected from the two most posterior teeth in the contra-lateral
      quadrants before and after a 30-second rinse with either distilled water (control
      group) or 0.1 ppm ozonated water (test group). The plaque was used to count the
      number of total bacteria, total anaerobic bacteria, Streptococcus mutans, and
      Candida albicans on selective agar media. The statistical analysis of the number
      of colony forming units (CFUs) obtained demonstrated a significant antimicrobial
      effect of ozonated water on the total bacteria (p = 0.01) and anaerobes (p =
      0.02). A reduction in the post-rinse CFU count for Streptococcus mutans was also
      observed, but the effect was not statistically significant (p = 0.07). The
      Candida species was only grown from one sample. Ozonated water at the 0.1 ppm
      concentration was effective in reducing the load of 24-hour plaque bacteria, but
      it did not eliminate them completely.

PMID- 22473348
TI  - Urban-rural differences in oral and maxillofacial trauma.
AB  - The aim of this research was to assess oral and maxillofacial trauma in urban and
      rural populations of the same region. The data collected included age, gender,
      year and month of trauma occurrence, origin (rural and urban), cause of injury,
      and the type of oral and maxillofacial trauma. Records from 1121 patients with
      790 instances of oral and maxillofacial trauma were evaluated. Statistical
      analysis was performed with the Statistical Package for Social Sciences (SPSS)
      version 17.0 software and involved descriptive statistics and Pearson's chi
      squared test. Male patients were more prone to maxillofacial trauma (n = 537;
      68%), and the patients were mostly from urban areas (n = 534; 67.6%). The male-to
      female ratio was found to be 2.12:1 (urban zone, 1.72:1; rural zone, 3.49:1). The
      average age was 25.7 years (SD = 14.1). A traffic accident was the most common
      cause of oral and maxillofacial trauma (27%). The jaw (18%) was the most commonly
      fractured bone in the facial skeleton, followed by the zygoma (12.9%). Avulsion
      (8.5%) was the most common dental trauma. A significant statistical relationship
      was found between place of origin and gender (p < 0.001). Accidents involving
      animals were more frequent in rural areas (P < 0.001). Zygomatic fractures (p <
      0.001), contusion (p = 0.003), and abrasion (p = 0.051) were the most common
      injuries among individuals from rural areas. Nasal fracture (p = 0.011) was the
      most frequent type of trauma in individuals from urban areas. According to these
      data, it seems reasonable to assume that specific preventive public policy for
      urban and rural areas must respect the differences of each region.

PMID- 22473349
TI  - Dental pulp stem cells express proteins involved in the local invasiveness of
      odontogenic myxoma.
AB  - Little is known about the histogenesis of the odontogenic myxoma (OM). Dental
      pulp stem cells could be candidate precursors of OM because both OM and the
      dental pulp share the same embryological origin: the dental papilla. For the
      purpose of comparing OM and stem cells, this study analyzed the expression of two
      proteins related to OM invasiveness (MMP-2 and hyaluronic acid) in human immature
      dental pulp stem cells (hIDPSCs). Three lineages of hIDPSCs from deciduous and
      permanent teeth were used in this study. Immunofluorescence revealed positive
      reactions for MMP-2 and hyaluronic acid (HA) in all hIDPSCs. MMP-2 appeared as
      dots throughout the cytoplasm, whereas HA appeared either as diffuse and
      irregular dots or as short fibrils throughout the cytoplasm and outside the cell
      bodies. The gene expression profile of each cell lineage was evaluated using RT
      PCR analysis, and HA was expressed more intensively than MMP-2. HA expression was
      similar among the three hIDPSCs lineages, whereas MMP-2 expression was higher in
      DL-1 than in the other cell lines. The expression of proteins related to OM
      invasiveness in hIDPSCs could indicate that OM originates from dental pulp stem
      cells.

PMID- 22473350
TI  - Skeletal maturation of the cervical vertebrae: association with various types of
      malocclusion.
AB  - The identification of the skeletal maturation stage of the cervical vertebrae has
      proven an important reference for orthodontic diagnosis. The aim of the present
      study was to determine the association between the skeletal maturation stage of
      the cervical vertebrae and types of malocclusion according to the age and gender
      of participants. A total of 361 individuals (168 males and 193 females) between 8
      and 14 years of age were selected from a convenience sample. Malocclusions were
      diagnosed through study models using the Angle classification. Maturation stages
      of the cervical vertebrae were determined using the method proposed by Hassel and
      Farman. Statistical analysis involved the chi-square test (p L 0.05) and multiple
      logistic regression (forward stepwise procedure). Significant differences were
      observed between the stage of skeletal maturation of the cervical vertebrae and
      gender at ages 11, 12 and 14 years. Males with Class II malocclusion were twice
      as likely to be in Stage 1 or 2 of cervical vertebra maturation than individuals
      with Class I malocclusion (OR = 2.1 [CI 95%, 1.33-3.18]). There were no
      differences between individuals with Class I and Class III malocclusions. The
      association between skeletal maturation of the cervical vertebrae and type of
      malocclusion was significant, suggesting a skeletal component in the
      determination of Class II malocclusions.

PMID- 22473351
TI  - Parental beliefs about children's teething in Udaipur, India: a preliminary
      study.
AB  - Throughout history, teething has been held responsible for a variety of childhood
      illnesses. The objective of this study was to assess parents' knowledge and
      beliefs about teething signs and symptoms and to investigate the practices used
      to alleviate teething troubles. A cross-sectional survey was conducted using a
      self-administered questionnaire distributed to 550 parents in Udaipur, India. The
      questionnaire contained three sections eliciting demographic characteristics and
      assessing parents' knowledge, beliefs, and practices regarding teething.
      Statistical analysis used descriptive statistics and the chi-squared test (p L
      0.05). Response to teething was incorrectly attributed to fever (70%), diarrhea
      (87.5%), and sleep disturbances (48.2%). Only 33.2% of parents allowed their
      children to bite on chilled objects to relieve symptoms associated with teething.
      A common lack of knowledge about teething among parents should encourage dental
      healthcare providers to educate them regarding the teething process and its
      management.

PMID- 22473352
TI  - Evaluation of the effect of an organic extract obtained from Ipomoea alba L. on
      experimental periodontitis in rats.
AB  - The aim of this study was to evaluate the effect of an organic extract obtained
      from Ipomoea alba L. (Convolvulaceae or OE 1493), on experimental periodontal
      disease in rats. Periodontitis was induced in thirty six Wistar rats: a first
      mandibular molar was randomly assigned to receive a ligature, whereas the
      contralateral molar was left unligated. Animals were randomly assigned to two
      groups and treated topically, three times a day, for 11 days, as follows: Control
      Group - vehicle-treated (n = 18), and Test Group - OE 1493-treated (n = 18). The
      rats were sacrificed on the 12th day. Morphometrical measurements from the
      cementoenamel junction to the bone crest were performed to determine alveolar
      bone loss, using standardized photographs. Single- and multi-dose acute toxicity
      assays were carried out after OE 1493 treatment. Morphometrical analysis
      demonstrated that topically-administered OE 1493 showed no effect on reducing
      bone loss when compared with the control group (p > 0.05). In addition, OE 1493
      did not present toxicity. Within the limits of this investigation, it may be
      concluded that OE 1493 did not show any positive influence on the progression of
      ligature-induced periodontitis in rats, when administered according to the
      regimen used in the present study.

PMID- 22473353
TI  - Influence of different shades and LED irradiance on the degree of conversion of
      composite resins.
AB  - The aim of this study was to evaluate the degree of conversion (DC) of two
      composite resins with different shades that were light cured by light-emitting
      diodes (LEDs) of different irradiances. Specimens (5 mm ' 2 mm) were prepared
      with a nanofilled (Filtek Supreme - A2E, A2D, and WE) or microhybrid resin
      (Opallis - A2E, A2D, and EBleach Low) and were randomly divided into 12 groups (n
      = 5 each) according to the composite resin and light-curing unit (Elipar
      FreeLight 2, 1250 mW/cm2; Ultralume 5, 850 mW/cm2). After 24 h, the DC was
      measured on two surfaces (top and bottom) with Fourier Transform infrared
      spectroscopy (FTIR). Data were statistically analyzed with two-way ANOVA and
      Tukey test (a = 0.05). Statistical differences among the surfaces were observed
      in all experimental conditions, with higher values on the top surface. The
      microhybrid resin presented the highest DCs for shades A2E and A2D on the top
      surface. The LED with higher irradiance promoted better DCs. Taken together, the
      data indicate that the shade of a composite resin and the irradiance of the light
      source affect the monomeric conversion of the restorative material.

PMID- 22473354
TI  - Effect of pre-heated dual-cured resin cements on the bond strength of indirect
      restorations to dentin.
AB  - This study evaluated the effects of resin luting agents (LA) polymerized using
      increased temperature on the in vitro microtensile bond strength (mTBS) of
      indirect restorations to dentin. The occlusal dentin surfaces of 40 human third
      molars were exposed and flattened. The teeth were assigned to 8 groups (n = 5)
      according to the LA temperature (25 degrees C o r 50 degrees C), curing mode
      (dual- or self-curing mode), and product (Excite DSC/Variolink II [VII] and XP
      Bond/Calibra [Cal]). The bonding agents were applied to the dentin surfaces
      according to manufacturers' instructions. For preheated groups, the LAs were
      heated to 50 degrees C, subsequently mixed on a heated stirrer surface, and
      applied to the previously heated pre-polymerized resin discs (2 mm thickness, TPH
      Spectrum). The discs were bonded to the dentin surfaces, and the LAs were either
      exposed to a curing light according to manufacturers' instructions or allowed to
      self-cure. Specimens were stored in relative humidity at 37 degrees C for 7 days.
      Specimens were mesio-distally and bucco-lingually sectioned to obtain multiple
      bonded beams with a 1-mm2 cross-sectional area for mTBS testing. Data (MPa) were
      analyzed by 2-way ANOVA and Tukey's post hoc test (a = 5%) for each product.
      Specimen failure patterns were analyzed using a scanning electron microscope. VII
      groups showed higher mTBS at 50 degrees C than at 25 degrees C regardless of
      curing mode (p = 0.05). Cal groups showed similar mTBS at 25 degrees C and 50
      degrees C in all activation modes. The use of some dual-polymerizing LAs at 50
      degrees C may improve the mTBS of indirect restorations to dentin.

PMID- 22473355
TI  - Effectiveness of immediate bonding of etch-and-rinse adhesives to simplified
      ethanol-saturated dentin.
AB  - This study examined the immediate bond strength of etch-and-rinse adhesives to
      demineralized dentin saturated with either water or absolute ethanol. The
      research hypothesis was that there would be no difference in bond strength to
      dentin between water or ethanol wet-bonding techniques. The medium dentin of 20
      third molars was exposed (n = 5). The dentin surface was then acid-etched, left
      moist and randomly assigned to be saturated via either water wet-bonding (WBT) or
      absolute ethanol wet-bonding (EBT). The specimens were then treated with one of
      the following etch-and-rinse adhesive systems: a 3-step, water-based system
      (Adper Scotchbond Multipurpose, or SBMP) or a 2-step, ethanol/water-based system
      (Adper Single Bond 2, or SB). Resin composite build-ups were then incrementally
      constructed. After water storage for 24 h at 37 degrees C, the tensile strength
      of the specimens was tested in a universal testing machine (0.5 mm/min). Data
      were analyzed by two-way ANOVA and Tukey's test (a = 5%). The failure modes were
      verified using a stereomicroscope (40'). For both adhesives, no significant
      difference in bond strength was observed between WBT and EBT (p > 0.05). The
      highest bond strength was observed for SB, regardless of the bonding technique (p
      < 0.05). No significant interaction between adhesives and bonding techniques was
      noticed (p = 0.597). There was a predominance of adhesive failures for all tested
      groups. The EBT and WBT displayed similar immediate bond strength means for both
      adhesives. The SB adhesive exhibited higher means for all conditions tested.
      Further investigations are needed to evaluate long-term bonding to dentin
      mediated by commercial etch-and-rinse adhesives using the EBT approach.

PMID- 22473356
TI  - New technology applications: Knotless barbed suture for tracheal resection
      anastomosis.
AB  - OBJECTIVES/HYPOTHESIS: Tracheal resection anastomoses are often under tension and
      can be technically challenging. New suture materials such as V-loc (barbed,
      knotless wound closure device) may offer advantages over conventional methods.
      The objective of this study is to determine if a running V-loc suture is of
      comparable tensile strength to conventional closure. STUDY DESIGN: Laboratory
      based study of human cadaveric tissue. METHODS: Fresh human cadaveric tracheas
      were dissected and incised into segments. Anastomosis of adjacent segments was
      then performed with either submucosal interrupted 3-0 Vicryl, or a running
      submucosal 3-0 V-loc suture. Anastomosed specimens were stretched to failure on
      an Instron force tension machine. Surgeon satisfaction was recorded by visual
      analog scale (VAS). RESULTS: The tensile strength of 12 tracheal anastomoses was
      tested. Video documentation of V-loc suture technique and anastomosis failure was
      recorded. In both Vicryl (80%) and V-loc (100%) anastomoses, failure occurred at
      the membranous intercartilaginous region. In 20% of the Vicryl anastomoses, the
      suture was noted to break prior to tissue failure. Anastomoses with V-loc suture
      had equivalent failure force (mean, 59 N) compared to interrupted Vicryl (51 N),
      with P = .57. On VAS, surgeons were more satisfied with V-loc suture closure
      compared to interrupted Vicryl closure (paired t test, P = .003). CONCLUSIONS:
      Tracheal anastomosis with running v-loc suture is a feasible alternative to
      conventional closure with interrupted Vicryl suture. V-loc suture provided a
      surgical advantage by improved ease of use.

PMID- 22473357
TI  - Group 11 complexes containing the [C5(CN)5]- ligand; 'coordination-analogues' of
      molecular organometallic systems.
AB  - The reactions of Na[C(5)(CN)(5)] (Na[1]) with group 11 phosphine complexes
      [(P)(n)MCl] (M = Cu, Ag, Au, P = Ph(3)P; M = Cu, P = dppe
      (Ph(2)PCH(2)CH(2)PPh(2))] give a range of compounds containing the
      pentacyanocyclopentadienide ligand, [C(5)(CN)(5)](-) (1). The new complexes
      [(Ph(3)P)(2)M{1}](2) [M = Cu (3); M = Ag (5)], [(Ph(3)P)(3)Ag{1}] (4),
      [(dppe)(3)Cu(2){1}(2)] (6) and [Au(PPh(3))(2)][1] (7) include the first complete
      series of group 11 complexes of any cyclopentadienide ligand to be structurally
      characterised.

PMID- 22473358
TI  - Photocaged permeability: a new strategy for controlled drug release.
AB  - Light is used to release a drug from a cell impermeable small molecule,
      uncloaking its cytotoxic effect on cancer cells.

PMID- 22473359
TI  - Rapid on-site evaluation of axillary fine-needle aspiration cytology in breast
      cancer.
AB  - BACKGROUND: Axillary ultrasonography (AUS) and fine-needle aspiration cytology
      (FNAC) can establish axillary lymph node status before surgery, although this
      technique is hampered by poor adequacy rates. To achieve consistently high rates
      of FNAC adequacy, rapid on-site evaluation (ROSE) of FNAC samples was introduced.
      METHODS: This single-centre, retrospective observational study of patients with
      newly diagnosed breast cancer undergoing preoperative AUS and FNAC between
      February 2008 and November 2010 examined the effect of the introduction of ROSE.
      RESULTS: A total of 381 patients were included. AUS revealed 152 axillae with
      suspicious radiological features. FNAC was positive for malignant cells in 75
      (49.3 per cent) of 152 samples. Sentinel lymph node mapping was avoided in 75
      patients, representing 19.7 per cent of the entire study population. Adequacy
      rates increased from 78 per cent to 96 per cent following the introduction of
      ROSE (P = 0.001). The overall sensitivity and specificity of AUS and FNAC was
      80.6 and 100 per cent respectively. A lymph node diameter equal to or larger than
      10 mm and extranodal extension were significantly associated with positive FNAC
      (P < 0.001 and P = 0.012 respectively). Maximum lymph node diameter of at least
      10 mm was an independent predictor of positive FNAC (odds ratio 11.2, 95 per cent
      confidence interval 3.32 to 37.76; P < 0.001). CONCLUSION: AUS with FNAC provided
      accurate preoperative staging of the axilla for metastatic breast disease and
      avoided unnecessary sentinel lymph node mapping. The introduction of ROSE ensured
      the efficiency of AUS and FNAC.

PMID- 22473360
TI  - Tungstate activates BK channels in a beta subunit- and Mg2+-dependent manner:
      relevance for arterial vasodilatation.
AB  - AIMS: Tungstate reduces blood pressure in experimental animal models of both
      hypertension and metabolic syndrome, although the underlying mechanisms are not
      fully understood. Given that the large-conductance voltage- and Ca(2+)-dependent
      K(+) (BK) channel is a key element in the control of arterial tone, our aim was
      to evaluate whether BK channel modulation by tungstate can contribute to its
      antihypertensive effect. METHODS AND RESULTS: Patch-clamp studies of
      heterologously expressed human BK channels (alpha + beta(1-4) subunits) revealed
      that cytosolic tungstate (1 mM) induced a significant left shift (~20 mV) in the
      voltage-dependent activation curve only in BK channels containing alphabeta(1) or
      alphabeta(4) subunits, but reduced the amplitude of K(+) currents through all BK
      channels tested. The beta(1)-dependent activation of BK channels by tungstate was
      enhanced at cytosolic Ca(2+) levels reached during myocyte contraction, and
      prevented either by removal of cytosolic Mg(2+) or by mutations rendering the
      channel insensitive to Mg(2+). A lower concentration of tungstate (0.1 mM)
      induced voltage-dependent activation of the vascular BKalphabeta(1) channel
      without reducing current amplitude, and consistently exerted a vasodilatory
      action on wild-type but not on beta(1)-knockout mouse arteries pre-contracted
      with endothelin-1. CONCLUSION: Tungstate activates BK channels in a beta subunit-
      and Mg(2+)-dependent manner and induces vasodilatation only in mouse arteries
      that express the BK beta(1) subunit.

PMID- 22473361
TI  - Cooperative effects of hydrogen, lithium and halogen bonding on F-H/LiOH2
      complexes.
AB  - A comparative computational study of the cooperative effect of hydrogen-, lithium
      and halogen-bonding on model F-H and F-Li complexes with H2O was undertaken at
      the MP2/6-311++G(d,p) level of theory. The general trend of increased attraction
      or a positive cooperative effect on introduction of a third molecule to the F
      H/LiOH2 dimer shows that lithium bonding has the greatest effect, followed by
      hydrogen bonding and then halogen bonding. The computed three-body nonadditive
      energy has a more substantial contribution to the interaction energy of the
      cyclic trimers than to the open linear trimer clusters. 

PMID- 22473362
TI  - Measles-containing vaccines and febrile seizures in children age 4 to 6 years.
AB  - BACKGROUND: In the United States, children receive 2 doses of measles-mumps
      rubella vaccine (MMR) and varicella vaccine (V), the first between ages 1 to 2
      years and the second between ages 4 to 6 years. Among 1- to 2-year-olds, the risk
      of febrile seizures 7 to 10 days after MMRV is double that after separate MMR +
      V. Whether MMRV or MMR + V affects risk for febrile seizure risk among 4- to 6
      year-olds has not been reported. METHODS: Among 4- to 6-year-old Vaccine Safety
      Datalink members, we identified seizures in the emergency department and hospital
      from 2000 to 2008 and outpatient visits for fever from 2006 to 2008 during days 7
      to 10 and 0 to 42 after MMRV and MMR + V. Incorporating medical record reviews,
      we assessed seizure risk after MMRV and MMR + V. RESULTS: From 2006 through 2008,
      86 750 children received MMRV; from 2000 through 2008, 67 438 received same-day
      MMR + V. Seizures were rare throughout days 0 to 42 without peaking during days 7
      to 10. There was 1 febrile seizure 7 to 10 days after MMRV and 0 after MMR + V.
      Febrile seizure risk was 1 per 86 750 MMRV doses (95% confidence interval, 1 per
      3 426 441, 1 per 15 570) and 0 per 67 438 MMR + V doses (1 per 18 282).
      CONCLUSIONS: This study provides reassurance that MMRV and MMR + V were not
      associated with increased risk of febrile seizures among 4- to 6-year-olds. We
      can rule out with 95% confidence a risk greater than 1 febrile seizure per 15 500
      MMRV doses and 1 per 18 000 MMR + V doses.

PMID- 22473363
TI  - Postnatal virilization mimicking 21-hydroxylase deficiency in 3 very premature
      infants.
AB  - Premature infants are known to have elevated 17-hydroxyprogesterone and adrenal
      androgen concentrations immediately after birth, but the levels decrease rapidly.
      Virilization of normal premature female infants as a result of these high
      androgens has not been described. Three premature female infants born at 24 to 25
      weeks' gestation, with birth weights 550 to 880 g and significant neonatal
      complications were noted to develop clitoromegaly 2 weeks to 3 months after
      birth. All 3 had elevated 17-hydroxyprogesterone >100 nmol/L and testosterone >3
      nmol/L concentrations. All were treated as simple virilizing 21-hydroxylase
      deficiency, but subsequent genetic analysis revealed no CYP21 mutations. Follow
      up after discontinuation of treatment revealed no recurrent virilization and
      normal adrenal steroid levels. Postnatal virilization in sick premature girls may
      occur, and investigations may suggest 21-hydroxylase deficiency. Genetic analysis
      of CYP21 should be performed before the diagnosis is confirmed. Further studies
      are needed to better document the natural history and possible causes of
      postnatal adrenal androgen secretion in sick premature infants.

PMID- 22473364
TI  - Association of malodorous urine with urinary tract infection in children aged 1
      to 36 months.
AB  - OBJECTIVE: To determine whether parental reporting of malodorous urine is
      associated with urinary tract infection (UTI) in children. METHODS: We conducted
      a prospective consecutive cohort study in the emergency department of a pediatric
      hospital from July 31, 2009 to April 30, 2011. All children aged between 1 and 36
      months for whom a urine culture was prescribed for suspected UTI (ie, unexplained
      fever, irritability, or vomiting) were assessed for eligibility. A standardized
      questionnaire was administered to the parents by a research assistant. The
      primary outcome measure was a UTI. RESULTS: Three hundred ninety-six children
      were initially enrolled, but 65 were excluded a posteriori either because a urine
      culture, although prescribed, was not done (11), was collected by bag (39),
      and/or showed gross contamination (25). Therefore, 331 children were included in
      the final analysis. Their median age was 12 months (range, 1-36). Criteria for
      UTI were fulfilled in 51 (15%). A malodorous urine was reported by parents in 57%
      of children with UTI and in 32% of children without UTI. On logistic regression,
      malodorous urine was associated with UTI (odds ratio 2.83, 95% confidence
      interval: 1.54-5.20). This association remained statistically significant when
      adjusted for gender and the presence of vesicoureteral reflux (odds ratio 2.73,
      95% confidence interval: 1.46-5.08). CONCLUSIONS: Parental reporting of
      malodorous urine increases the probability of UTI among young children being
      evaluated for suspected UTI. However, this association is not strong enough to
      definitely rule in or out a diagnosis of UTI.

PMID- 22473365
TI  - Maternal caffeine consumption and infant nighttime waking: prospective cohort
      study.
AB  - OBJECTIVE: Coffee and other caffeinated beverages are commonly consumed in
      pregnancy. In adults, caffeine may interfere with sleep onset and have a dose
      response effect similar to those seen during insomnia. In infancy, nighttime
      waking is a common event. With this study, we aimed to investigate if maternal
      caffeine consumption during pregnancy and lactation leads to frequent nocturnal
      awakening among infants at 3 months of age. METHODS: All children born in the
      city of Pelotas, Brazil, during 2004 were enrolled on a cohort study. Mothers
      were interviewed at delivery and after 3 months to obtain information on caffeine
      drinking consumption, sociodemographic, reproductive, and behavioral
      characteristics. Infant sleeping pattern in the previous 15 days was obtained
      from a subsample. Night waking was defined as an episode of infant arousal that
      woke the parents during nighttime. Multivariable analysis was performed by using
      Poisson regression. RESULTS: The subsample included 885 of the 4231 infants born
      in 2004. All but 1 mother consumed caffeine in pregnancy. Nearly 20% were heavy
      consumers (>=300 mg/day) during pregnancy and 14.3% at 3 months postpartum.
      Prevalence of frequent nighttime awakeners (>3 episodes per night) was 13.8% (95%
      confidence interval: 11.5%-16.0%). The highest prevalence ratio was observed
      among breastfed infants from mothers consuming >=300 mg/day during the whole
      pregnancy and in the postpartum period (1.65; 95% confidence interval: 0.86-3.17)
      but at a nonsignificant level. CONCLUSIONS: Caffeine consumption during pregnancy
      and by nursing mothers seems not to have consequences on sleep of infants at the
      age of 3 months.

PMID- 22473367
TI  - Tenfold medication errors: 5 years' experience at a university-affiliated
      pediatric hospital.
AB  - BACKGROUND AND OBJECTIVES: Tenfold medication errors are a significant source of
      risk to pediatric patients. This may be because of wide variations in age,
      weight, dosing ranges, and off-label practices, but few studies exclusively
      devoted to examining pediatric 10-fold error have identified the circumstances
      and mechanisms that lead to such errors. We examined all 10-fold medication
      errors reported within an academic, university-affiliated pediatric hospital to
      make recommendations for future initiatives that could improve medication safety
      in pediatric practice. METHODS: We retrospectively evaluated all medication
      related incident reports submitted to a voluntary safety-reporting database over
      a 5-year period for reports describing 10-fold medication error. Main outcome
      measures comprised severity of error, drugs and drug classes involved, 10-fold
      medication error enablers, mechanisms, and contributing causes. RESULTS: From
      6643 medication-related safety reports, 252 10-fold medication errors were
      identified at a mean reporting rate of 0.062 per 100 total patient days. Morphine
      was the most frequently reported medication, and opioids were the most frequently
      reported drug class. Twenty-two reports described patient harm. Intravenous
      formulations, paper ordering, and drug-delivery pumps were frequent error
      enablers. Errors of dose calculation, documentation of decimal points, and
      confusion with zeroes were frequent contributing causes to 10-fold medication
      error. CONCLUSIONS: This study exclusively and comprehensively examined 10-fold
      medication errors over a prolonged time in pediatric inpatients. We discuss
      recommendations of vigilance for specific drugs and standardized order sets for
      opioids and antibiotics, and identify the administering phase of the medication
      process as a high-risk practice that can result in pediatric 10-fold medication
      error.

PMID- 22473368
TI  - Inside Millennium Development Goal 4.

PMID- 22473366
TI  - The human microbiome and its potential importance to pediatrics.
AB  - The human body is home to more than 1 trillion microbes, with the
      gastrointestinal tract alone harboring a diverse array of commensal microbes that
      are believed to contribute to host nutrition, developmental regulation of
      intestinal angiogenesis, protection from pathogens, and development of the immune
      response. Recent advances in genome sequencing technologies and metagenomic
      analysis are providing a broader understanding of these resident microbes and
      highlighting differences between healthy and disease states. The aim of this
      review is to provide a detailed summary of current pediatric microbiome studies
      in the literature, in addition to highlighting recent findings and advancements
      in studies of the adult microbiome. This review also seeks to elucidate the
      development of, and factors that could lead to changes in, the composition and
      function of the human microbiome.

PMID- 22473369
TI  - High blood pressure in 2.5-year-old children born extremely preterm.
AB  - OBJECTIVE: Adolescents and young adults born preterm have elevated blood pressure
      (BP). The objective of this study was to investigate if BP is elevated at 2.5
      years of age after an extremely preterm birth (EXPT). METHODS: In a regional
      subset of the national population-based cohort Extremely Preterm Infants in
      Sweden Study, BP at 2.5 years of age was studied in 68 survivors of EXPT
      (gestational age: 23.6-26.9 weeks; mean +/- SD birth weight: 810 +/- 164 g), and
      65 matched controls born at term. RESULTS: At follow-up at 2.5 years of corrected
      age, EXPT children had significantly higher systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) z scores than controls born at term, according to
      pediatric BP nomograms by age, gender, and height. The proportion of SBP >=90th
      percentile was 44% (30 of 68) in EXPT children and 23% (15 of 65) in controls (P
      = .01). In logistic regression analyses stratified according to gender, EXPT was
      associated with an odds ratio for a SBP >=90th percentile of 3.32 (95% confidence
      interval: 1.25-8.81) among boys. The corresponding odds ratio among EXPT girls
      was 2.18 (95% confidence interval: 0.62-7.61). In EXPT children, SBP and DBP z
      scores were inversely correlated to catch-up growth from 36 weeks' postmenstrual
      age to follow-up at 2.5 years of age. CONCLUSIONS: Children born extremely
      preterm have elevated office SBP and DBP at a corrected age of 2.5 years. This
      finding might have implications for their cardiovascular health later in life.

PMID- 22473370
TI  - Long-term reduction in adverse drug events: an evidence-based improvement model.
AB  - OBJECTIVES: To develop and test an evidence-based model for reducing medication
      errors and harm in hospitalized children. METHODS: Prospective interrupted time
      series study evaluating the effectiveness of a multifaceted, staged intervention
      over 4 years in a major urban pediatric referral hospital. Guidelines for safe
      pediatric prescribing were implemented by using an evidence-based model. Key
      components included early clinician engagement and improved multidisciplinary
      communication, consensus development, interactive education, and timely data
      feedback by using iterative Plan-Do-Study-Act cycles. Impact on medication error
      and harm (adverse drug events, [ADEs]) was measured by using standard definitions
      and a multimethod approach. Prospective data from voluntary reports by nursing,
      medical, and pharmacy staff and intensive chart review were combined. All data
      were reviewed by a multidisciplinary panel, including causality assessments for
      ADEs. RESULTS: Reviewed over 3 time periods were 1011 patients with 6651
      medication orders. Total ADEs decreased by > 50% in the first year and this was
      maintained at 4 years. Greatest improvements were in potential ADEs, which
      decreased from 12.26 per 100 patients at baseline to 4.60 per 100 patients at 4
      years (P < .05). Total medication errors decreased from 4.51 per 100 orders at
      baseline to 2.78 per 100 orders at 4 years (P < .05). Prescribing errors
      decreased by 65%, from 4.07 per 100 orders at baseline to 2.05 orders at 4 years
      (P < .05). CONCLUSIONS: A multifaceted, evidence-based model for safe prescribing
      guideline implementation, engaging multidisciplinary clinicians, was effective in
      reducing medication error and harm in hospitalized children, resulting in
      sustained long-term improvement.

PMID- 22473371
TI  - Obese Mexican American children have elevated MCP-1, TNF-alpha, monocyte
      concentration, and dyslipidemia.
AB  - BACKGROUND AND OBJECTIVE: Obesity is an independent risk factor for chronic
      disease. The prevalence of obesity is especially high among Mexican American
      children. Peripheral blood monocytes are altered with obesity contributing to
      elevated systemic inflammation and increased risk of chronic disease. In
      addition, obesity alters the circulating levels of cytokines/chemokines that
      influence monocyte behavior. The study objective was to investigate alterations
      in blood monocytes and plasma cytokines/chemokine levels among healthy weight
      (standardized BMI [zBMI] <=85th percentile; n = 66), overweight (zBMI 85th-95th
      percentile; n = 23), and obese (zBMI >=95th percentile; n = 39) Mexican American
      children. METHODS: Blood samples were analyzed for total and subset monocyte
      concentration via flow cytometry. Serum monocyte chemoattractant protein-1 (MCP
      1), fractalkine, interleukin-8, and tumor necrosis factor alpha (TNF-alpha) were
      measured by using a Milliplex MagPix assay. Serum cholesterol, high-density
      lipoproteins, triglycerides, and glucose were measured by using an enzymatic
      assay. RESULTS: Total monocyte concentration (P = .012), classic monocyte
      concentration (P = .045), MCP-1 (P = .015), and TNF-alpha (P = .002) were
      significantly greater in obese children compared with healthy weight children.
      Also, overweight and obese children had elevated triglycerides (P = .001) and
      reduced high-density lipoproteins (P = .033) compared with healthy weight
      children. CONCLUSIONS: Childhood obesity alters monocytes and circulating
      chemokines, putting children at a greater risk of developing obesity-related
      chronic diseases in adulthood. Further characterization of early immune
      alterations in childhood obesity may provide additional clinical insight into the
      assessment of obesity-related disease risk.

PMID- 22473372
TI  - Six developmental trajectories characterize children with autism.
AB  - OBJECTIVE: The goal of this study was to describe the typical longitudinal
      developmental trajectories of social and communication functioning in children
      with autism and to determine the correlates of these trajectories. METHODS:
      Children with autism who were born in California from 1992 through 2001 and
      enrolled with the California Department of Developmental Services were
      identified. Subjects with <4 evaluations present in the database were excluded,
      resulting in a sample of 6975 children aged 2 to 14 years. Score sequences were
      constructed based on 9 evaluative items for social, communication, and repetitive
      behavior functioning. Typical trajectories were identified by using group-based
      latent trajectory modeling, and multinomial logistic regression models were used
      to determine the odds of classification within each trajectory varied by
      individual and family-level factors. RESULTS: Six typical patterns of social,
      communication, and repetitive behavior functioning were identified. These
      trajectories displayed significant heterogeneity in developmental pathways, and
      children whose symptoms were least severe at first diagnosis tended to improve
      more rapidly than those severely affected. One group of ~10% of children
      experienced rapid gains, moving from severely affected to high functioning.
      Socioeconomic factors were correlated with trajectory outcomes; children with non
      Hispanic, white, well-educated mothers were more likely to be high functioning,
      and minority children with less-educated mothers or intellectual disabilities
      were very unlikely to experience rapid gains. CONCLUSIONS: Children with autism
      have heterogeneous developmental pathways. One group of children evidenced
      remarkable developmental change over time. Understanding what drives these
      outcomes is thus critical.

PMID- 22473374
TI  - The effect of the school environment on the emotional health of adolescents: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVES: The evidence base for the importance of the school
      environment for adolescent emotional health has never been systematically
      reviewed. We aimed to synthesize the evidence for the effect on adolescent
      emotional health of (1) interventions targeting the school environment and (2)
      the school environment in cohort studies. METHODS: Searches of Medline, Embase,
      PsychINFO, CINAHL, ERIC, the Social Citation Index, and the gray literature were
      conducted. Criteria for inclusion were (1) cohort or controlled trial designs,
      (2) participants aged 11 to 18 years, (3) emotional health outcomes, and (4)
      school environment exposure or intervention. Relevant studies were retrieved and
      data extracted by 2 independent reviewers. RESULTS: Nine papers reporting 5
      controlled trials were reviewed, along with 30 cohort papers reporting 23
      studies. Two nonrandomized trials found some evidence that a supportive school
      environment improved student emotional health, but 3 randomized controlled trials
      did not. Six (20%) cohort papers examined school-level factors but found no
      effect. There was some evidence that individual perceptions of school
      connectedness and teacher support predict future emotional health. Multilevel
      studies showed school effects were smaller than individual-level effects.
      Methodological shortcomings were common. CONCLUSIONS: There is limited evidence
      that the school environment has a major influence on adolescent mental health,
      although student perceptions of teacher support and school connectedness are
      associated with better emotional health. More studies measuring school-level
      factors are needed. Randomized controlled trials evaluating 1 or 2 environmental
      components may have more success in establishing effective and feasible
      interventions compared with complex whole-school programs.

PMID- 22473373
TI  - Relationship between maternal and neonatal Staphylococcus aureus colonization.
AB  - OBJECTIVE: The study aimed to assess whether maternal colonization with
      Staphylococcus aureus during pregnancy or at delivery was associated with infant
      staphylococcal colonization. METHODS: For this prospective cohort study, women
      were enrolled at 34 to 37 weeks of gestation between 2007 and 2009. Nasal and
      vaginal swabs for culture were obtained at enrollment; nasal swabs were obtained
      from women and their infants at delivery and 2- and 4-month postbirth visits.
      Logistic regression was used to determine whether maternal colonization affected
      infant colonization. RESULTS: Overall, 476 and 471 mother-infant dyads had
      complete data for analysis at enrollment and delivery, respectively. Maternal
      methicillin-resistant S aureus (MRSA) colonization occurred in 10% to 17% of
      mothers, with the highest prevalence at enrollment. Infant MRSA colonization
      peaked at 2 months of age, with 20.9% of infants colonized. Maternal
      staphylococcal colonization at enrollment increased the odds of infant
      staphylococcal colonization at birth (odds ratio; 95% confidence interval: 4.8;
      2.4-9.5), hospital discharge (2.6; 1.3-5.0), at 2 months of life (2.7; 1.6-4.3),
      and at 4 months of life (2.0; 1.1-3.5). Similar results were observed for
      maternal staphylococcal colonization at delivery. Fifty maternal-infant dyads had
      concurrent MRSA colonization: 76% shared isolates of the same pulsed-field type,
      and 30% shared USA300 isolates. Only 2 infants developed staphylococcal disease.
      CONCLUSIONS: S aureus colonization (including MRSA) was extremely common in this
      cohort of maternal-infant pairs. Infants born to mothers with staphylococcal
      colonization were more likely to be colonized, and early postnatal acquisition
      appeared to be the primary mechanism.

PMID- 22473375
TI  - In vitro transcription and capping of Gaussia luciferase mRNA followed by HeLa
      cell transfection.
AB  - In vitro transcription is the synthesis of RNA transcripts by RNA polymerase from
      a linear DNA template containing the corresponding promoter sequence (T7, T3,
      SP6) and the gene to be transcribed (Figure 1A). A typical transcription reaction
      consists of the template DNA, RNA polymerase, ribonucleotide triphosphates, RNase
      inhibitor and buffer containing Mg(2+) ions.    Large amounts of high quality RNA
      are often required for a variety of applications. Use of in vitro transcription
      has been reported for RNA structure and function studies such as splicing(1),
      RNAi experiments in mammalian cells(2), antisense RNA amplification by the
      "Eberwine method"(3), microarray analysis(4) and for RNA vaccine studies(5). The
      technique can also be used for producing radiolabeled and dye labeled probes(6).
      Warren, et al. recently reported reprogramming of human cells by transfection
      with in vitro transcribed capped RNA(7). The T7 High Yield RNA Synthesis Kit from
      New England Biolabs has been designed to synthesize up to 180 MUg RNA per 20 MUl
      reaction. RNA of length up to 10kb has been successfully transcribed using this
      kit. Linearized plasmid DNA, PCR products and synthetic DNA oligonucleotides can
      be used as templates for transcription as long as they have the T7 promoter
      sequence upstream of the gene to be transcribed.    Addition of a 5' end cap
      structure to the RNA is an important process in eukaryotes. It is essential for
      RNA stability(8), efficient translation(9), nuclear transport(10) and
      splicing(11). The process involves addition of a 7-methylguanosine cap at the 5'
      triphosphate end of the RNA. RNA capping can be carried out post
      transcriptionally using capping enzymes or co-transcriptionally using cap
      analogs. In the enzymatic method, the mRNA is capped using the Vaccinia virus
      capping enzyme(12,13). The enzyme adds on a 7-methylguanosine cap at the 5' end
      of the RNA using GTP and S-adenosyl methionine as donors (cap 0 structure). Both
      methods yield functionally active capped RNA suitable for transfection or other
      applications(14) such as generating viral genomic RNA for reverse-genetic
      systems(15) and crystallographic studies of cap binding proteins such as
      eIF4E(16).    In the method described below, the T7 High Yield RNA Synthesis Kit
      from NEB is used to synthesize capped and uncapped RNA transcripts of Gaussia
      luciferase (GLuc) and Cypridina luciferase (CLuc). A portion of the uncapped GLuc
      RNA is capped using the Vaccinia Capping System (NEB). A linearized plasmid
      containing the GLuc or CLuc gene and T7 promoter is used as the template DNA. The
      transcribed RNA is transfected into HeLa cells and cell culture supernatants are
      assayed for luciferase activity. Capped CLuc RNA is used as the internal control
      to normalize GLuc expression.

PMID- 22473376
TI  - Robert Zajonc: The Complete Psychologist.
AB  - This article joins with others in the same issue to celebrate the career of
      Robert B. Zajonc who was a broad, as well as deeply talented, psychologist.
      Beyond his well-known focus in social psychology, the work of Zajonc also
      involved, at one time or another, forays into nearly every other subfield of
      psychology. This article focuses specifically on his studies that extended into
      biopsychology, which deserve special highlighting in order to be recognized
      alongside his many major achievements in emotion and related social topics. The
      biopsychological focus is offered here in the hope that all his diverse
      contributions be savored together when celebrating the complete psychology of
      Robert Zajonc.

PMID- 22473377
TI  - Reconstruction and electronic properties of silicon nanosheets as a function of
      thickness.
AB  - We have shown, using density functional theory calculations, that the properties
      of Si nanosheets change as a function of thickness. While Si(111) oriented
      nanosheets that are 0.56 nm thick (2-layers) display a novel reconstruction,
      classified as Si(111)-2 * 2 on both surface layers (T. Morishita, M. J. S.
      Spencer, S. P. Russo, I. K. Snook and M. Mikami, Chem. Phys. Lett., 2011, 506,
      221), nanosheets that are up to a thickness of 1.42 nm show the Si(111)-2 * 1
      surface reconstruction, that is seen on the bulk Si(111) surface, on both sides
      of the nanosheet. For these thicker nanosheets, the relative orientation of the
      pi-chain structure on each surface of the nanosheet can either be the same or
      different, resulting in unique electronic properties. When the orientation is the
      same, there is a widening of the band gap, indicating that the interaction
      between the surface pi-chains is not present when they are oriented in different
      directions. The electronic properties of the nanosheets approach those of the
      bulk by 1.42 nm thick. The variation in structural and electronic properties of
      Si nanosheets with different thicknesses, as shown in this study, highlights the
      novelty of these materials and their significance for applications in electronic
      device technologies.

PMID- 22473378
TI  - A theoretical study on photomagnetic fluorescent protein chromophore coupled
      diradicals and their possible applications.
AB  - We have designed and theoretically studied three different pairs of green
      fluorescent protein chromophores and their different homologue-based diradicals
      coupled with imino nitroxides. To begin with, the geometries of all these
      diradicals have been optimized at high spin (HS) state in the gas phase, in a
      water medium and in a blood plasma medium. The process of calculations is
      straightforward and well-established in the case of the gas phase. However, for
      calculations in water, we have adopted our own N-layer integrated molecular
      orbital and molecular mechanics (ONIOM) method. Similarly for the blood phase
      calculations, the polarized continuum model (PCM) method has been adopted. With
      these optimized geometries the magnetic exchange coupling constant (J) values are
      estimated for these diradicals in different media using the broken symmetry (BS)
      approach in an unrestricted DFT framework. In order to obtain the BS solutions in
      the ONIOM method, we have carried out ONIOM-BS, where the BS calculations are
      done for the inner high-level layer (diradical system) keeping the outer water
      layer at low level. In a similar fashion, a PCM-BS technique has also been
      adopted for the BS calculations in the PCM method. We have found that these
      diradicals have an ability to change their magnetic nature from antiferromagnetic
      in the trans form to ferromagnetic in the cis form upon irradiation of light with
      the appropriate wavelength. Using a time-dependent DFT (TDDFT) technique, the
      required wavelengths of light by which non-fluorescent dark trans diradicals turn
      into their corresponding bright fluorescent cis isomers are determined for each
      pair of diradicals for the gas and water media. This color change is indeed a
      signature of the change in magnetic state of the diradicals concerned. Here, we
      have also calculated the zero field splitting (ZFS) parameter (D), rhombic ZFS
      parameter (E) and ZFS magnitude (a2). From our calculations we ambitiously expect
      that if these diradicals are synthesized then they might be used as a successful,
      non-hazardous magnetic resonance imaging contrast agent (MRICA) in place of other
      metal-based contrast agents. 

PMID- 22473379
TI  - Genome evolution: Mapping recombination in chimpanzees.

PMID- 22473380
TI  - From patients to partners: participant-centric initiatives in biomedical
      research.
AB  - Advances in computing technology and bioinformatics mean that medical research is
      increasingly characterized by large international consortia of researchers that
      are reliant on large data sets and biobanks. These trends raise a number of
      challenges for obtaining consent, protecting participant privacy concerns and
      maintaining public trust. Participant-centred initiatives (PCIs) use social media
      technologies to address these immediate concerns, but they also provide the basis
      for long-term interactive partnerships. Here, we give an overview of this rapidly
      moving field by providing an analysis of the different PCI approaches, as well as
      the benefits and challenges of implementing PCIs.

PMID- 22473381
TI  - Complex traits: Old meets new in obesity genetics.

PMID- 22473382
TI  - Technology: Breeding vigour backwards.

PMID- 22473384
TI  - Epidemiological study and clinical profile of Parkinson's disease in the Assiut
      Governorate, Egypt: a community-based study.
AB  - BACKGROUND: Few comprehensive epidemiological studies of the prevalence of
      Parkinson's disease (PD) have been undertaken in Arab countries, and none has
      been carried out in Egypt. A community-based survey was conducted in the Assiut
      Governorate to estimate the prevalence and clinical profile of PD. METHODS: A
      community-based study was carried out, with random sampling of 7 districts,
      involving 6,498 inhabitants. Out of this sample, 578 subjects dropped out,
      leaving 3,066 males (51.8%) and 2,854 females (48.2%). There were 3,660 urban
      residents (61.8%) and 2,260 (38.2%) from the rural community. Patients were
      evaluated using a screening questionnaire, the Unified Parkinson Disease Rating
      Scale and the Non-Motor Symptoms Scale for PD. RESULTS: Thirty-nine subjects were
      found to have parkinsonism, giving a crude prevalence rate of 659/100,000
      inhabitants. Of these subjects, 33 were diagnosed with PD (21 males), with a mean
      age of 66.9 +/- 8.4 years, a crude prevalence rate of 557/100,000 and an age
      specific prevalence rate (>=50 years old) of 2,748/100,000. There were more males
      than females (3,395 vs. 1,989/100,000), but the difference was not significant.
      The highest age-specific prevalence rate was recorded among subjects 70-79 years
      old (7,263/100,000). There was a significantly higher prevalence among rural than
      urban inhabitants (973 vs. 301/100,000) and among illiterate than literate
      persons (1,103 vs. 280/100,000). The clinical profile of our patients was similar
      to that of other populations but was characterized by a high prevalence of
      mood/cognition dysfunction and gastrointestinal symptoms; there were few reported
      perceptual problems. CONCLUSION: The overall prevalence of PD was high,
      especially in older adults.

PMID- 22473385
TI  - In situ synthesis of Cu-BTC (HKUST-1) in macro-/mesoporous silica monoliths for
      continuous flow catalysis.
AB  - The metal-organic framework Cu-BTC has been successfully synthesized as
      nanoparticles inside the mesopores of silica monoliths featuring a homogeneous
      macropore network enabling the use of Cu-BTC for continuous flow applications in
      liquid phase with low pressure drop. High productivity was reached with this
      catalyst for the Friedlander reaction.

PMID- 22473383
TI  - Histone methylation: a dynamic mark in health, disease and inheritance.
AB  - Organisms require an appropriate balance of stability and reversibility in gene
      expression programmes to maintain cell identity or to enable responses to
      stimuli; epigenetic regulation is integral to this dynamic control. Post
      translational modification of histones by methylation is an important and
      widespread type of chromatin modification that is known to influence biological
      processes in the context of development and cellular responses. To evaluate how
      histone methylation contributes to stable or reversible control, we provide a
      broad overview of how histone methylation is regulated and leads to biological
      outcomes. The importance of appropriately maintaining or reprogramming histone
      methylation is illustrated by its links to disease and ageing and possibly to
      transmission of traits across generations.

PMID- 22473389
TI  - Low density ionogels obtained by rapid gellification of tetraethyl orthosilane
      assisted by ionic liquids.
AB  - A non-hydrolytic one pot sol-gel method has been used to synthesize mesoporous
      silica ionogels with the confined ionic liquid (IL) 1-ethyl 3-methyl imidazolium
      tetra fluoro-borate [EMIM][BF(4)]. The precursor for obtaining the SiO(2) matrix
      was tetraethyl orthosilicate (TEOS) and formic acid was used as a catalyst. These
      ionogels have been characterized by density measurements, TEM, BET, DSC, TGA and
      FTIR. The incorporation of the ionic liquid [EMIM][BF(4)] enhances the
      gellification rate which results in the ionogels having very low density (~0.3 g
      cm(-3)). The low density has been explained on the basis of the creation of
      'blind embedded pores' in the matrix (apart from open pores) due to very rapid
      gellification (~1 min). Morphological studies provide experimental evidence for
      the presence of blind pores/voids inside the ionogel ingots. We have also shown
      that the IL entrapped in nanopores (~7-8 nm pore size) of the SiO(2) matrix has
      different physical properties than the bulk IL viz. (a) the phase transition
      temperatures (T(g), T(c) and T(m)) of the IL change upon confinement, (b) the
      thermal stability reduces upon confinement, and (c) the pore wall interaction
      with the IL results in changes in the C-H vibrations of the imidazolium ring and
      alkyl chain (the former increasing) which is also indicated in our DFT
      calculation.

PMID- 22473387
TI  - Neuronal populations in the basolateral nuclei of the amygdala are differentially
      increased in humans compared with apes: a stereological study.
AB  - In human and nonhuman primates, the amygdala is known to play critical roles in
      emotional and social behavior. Anatomically, individual amygdaloid nuclei are
      connected with many neural systems that are either differentially expanded or
      conserved over the course of primate evolution. To address amygdala evolution in
      humans and our closest living relatives, the apes, we used design-based
      stereological methods to obtain neuron counts for the amygdala and each of four
      major amygdaloid nuclei (the lateral, basal, accessory basal, and central nuclei)
      in humans, all great ape species, lesser apes, and one monkey species. Our goal
      was to determine whether there were significant differences in the number or
      percent of neurons distributed to individual nuclei among species. Additionally,
      regression analyses were performed on independent contrast data to determine
      whether any individual species deviated from allometric trends. There were two
      major findings. In humans, the lateral nucleus contained the highest number of
      neurons in the amygdala, whereas in apes the basal nucleus contained the highest
      number of neurons. Additionally, the human lateral nucleus contained 59% more
      neurons than predicted by allometric regressions on nonhuman primate data. Based
      on the largest sample ever analyzed in a comparative study of the hominoid
      amygdala, our findings suggest that an emphasis on the lateral nucleus is the
      main characteristic of amygdala specialization over the course of human
      evolution.

PMID- 22473390
TI  - Inhibin alpha gene promoter polymorphisms in Korean women with idiopathic
      premature ovarian failure.
AB  - BACKGROUND: It has been suggested that variations in the inhibin alpha gene
      (INHA) may affect the ovarian function of women. This study was performed to
      investigate whether the genetic polymorphisms of the INHA gene are associated
      with idiopathic premature ovarian failure (POF) in a Korean population. METHODS:
      The subjects consisted of 159 idiopathic POF patients and 233 post-menopausal
      controls. Genotyping for the -16C>T polymorphism was performed by an minor groove
      binder (MGB) primer/probe Taqman assay, and the -124A>G polymorphism was
      identified using PCR restriction fragment length polymorphism analysis.
      Haplotypes were deduced by using the Haploview version 4.1. RESULTS: There were
      no significant differences in the genotype distributions or allele frequencies of
      the INHA gene -16C>T and -124A>G polymorphisms between the POF and the control
      group. Haplotype analysis also showed no significant difference between groups.
      CONCLUSIONS: The distribution of the INHA gene promoter polymorphisms in a Korean
      POF population was not significantly different from controls, implying that the
      INHA gene polymorphisms may not be associated with the risk of idiopathic POF.

PMID- 22473391
TI  - No evidence of somatic DNA copy number alterations in eutopic and ectopic
      endometrial tissue in endometriosis.
AB  - BACKGROUND: De novo somatic copy number aberrations (SCNAs) in eutopic and
      ectopic endometria are thought to be involved in the pathogenesis of
      endometriosis. In this study we used, for the first time, high-density single
      nucleotide polymorphism-array technology for accurate detection of SCNAs,
      inherited DNA copy number variations (CNVs) and copy-neutral loss of
      heterozygosity (cn-LOH) patterns in patients with endometriosis. METHODS: The
      Illumina HumanOmniExpress array was used to detect de novo somatic genomic
      alterations in eutopic and ectopic endometria from 11 women (eight with Stage I
      II endometriosis and three with Stage III-IV endometriosis) by comparatively
      analysing DNA from peripheral blood, eutopic endometrium and a pure population of
      endometriotic cells harvested from endometriotic lesions by laser capture
      microdissection (LCM). The frequency of the CNV in 3p14.1 from blood DNA of 187
      endometriosis patients (94 with Stage I-II endometriosis and 93 with Stage III-IV
      endometriosis) and 171 healthy women from the Estonian general population was
      evaluated. RESULTS: Analysis of array data showed that LCM DNA can be used
      successfully for detection of genetic changes as all inherited CNVs were
      identified in all tissues studied. No unique SCNAs or cases of cn-LOH were found
      in either eutopic or ectopic endometrium when compared with blood DNA. The
      frequency of the deletion allele in 3p14.1 did not differ between studied groups.
      CONCLUSIONS: In the present study no endometriosis-specific SCNAs or regions of
      cn-LOH in eutopic or ectopic endometrium were found. Nevertheless, as we studied
      only 17 endometriotic tissues derived from 11 patients we cannot entirely exclude
      the occurrence of rare SCNAs. Based on our results we suggest that molecular
      mechanisms other than chromosomal rearrangements most likely underlie the onset
      and progression of endometriosis.

PMID- 22473392
TI  - Paired-box gene 2 is down-regulated in endometriosis and correlates with low
      epidermal growth factor receptor expression.
AB  - BACKGROUND: Paired-box 2 (Pax2) is involved in the development of the female
      genital tract and has been associated with endometrial pathologies. The
      expression of Pax2 is induced by epidermal growth factor (EGF) and estrogens. In
      the present study, Pax2 expression and regulation were investigated in
      endometriosis. METHODS AND RESULTS: Pax2 protein expression was assessed by
      immunohistochemistry in the eutopic (i.e. inside the uterus) and ectopic tissue
      (endometriosis) from 11 patients. Immunoreactivity was high in the endometrium,
      with strong epithelial and weaker stromal staining. Similar expression patterns
      of Pax2 were observed in the endometrium of women without endometriosis (n = 12).
      The mRNA level of Pax2 was assessed by real-time PCR in the eutopic and ectopic
      endometria of 14 patients and in the endometrium from women without endometriosis
      (n = 20). Pax2 expression was lower in endometriotic lesions than that in the
      eutopic endometrium of patients (P< 0.001) and controls (P= 0.007). Three
      possible mechanisms determining low Pax2 expression were investigated: EGF
      signalling, CpG DNA methylation of the Pax2 promoter and steroid response. The
      mRNA level of the EGF receptor (EGFR1) was assessed in the samples used for Pax2
      mRNA assessment. A significant correlation between EGFR1 and Pax2 in both eutopic
      and ectopic tissues was observed (R = 0.58; slope regression line, 0.81; 95% CI:
      0.09-1.52 and R = 0.54; slope regression line, 2.51; 95% CI: 0.02-4.99,
      respectively). CpG DNA methylation was analyzed by methyl-specific PCR in two
      regions of the Pax2 promoter but they were unmethylated in all samples. Steroid
      responsiveness was assessed using endometrial explant cultures and Pax2 was not
      regulated by either 17beta-estradiol or progesterone. CONCLUSIONS: In
      endometriosis patients, Pax2 is down-regulated in the lesions compared with the
      eutopic tissue, possibly due to low EGF signalling.

PMID- 22473393
TI  - AMH for predicting poor ovarian responders in GnRH antagonist cycles.

PMID- 22473394
TI  - Effect of an oral contraceptive on emotional distress, anxiety and depression of
      women with polycystic ovary syndrome: a prospective study.
AB  - STUDY QUESTION: We aimed to determine the impact of an oral contraceptive (OC)
      treatment on health-related quality of life (HRQOL), depressive and anxiety
      symptoms in polycystic ovary syndrome (PCOS). SUMMARY ANSWER: OC therapy in PCOS
      improves hirsutism and menstrual disturbances, along with HRQOL. This improvement
      is not associated with any change in the prevalence of depressive and anxiety
      symptoms. WHAT IS KNOWN AND WHAT THIS ARTICLE ADDS: Limited data are available
      regarding the effects of an OC on HRQOL, and depressive and anxiety symptoms in
      PCOS. This study reports the effects of the ethinyl estradiol/drospirenone
      (EE/DRSP) OC on an HRQOL questionnaire for women with PCOS (PCOSQ), depressive
      and anxiety symptoms after 6 months of treatment. DESIGN: Prospective
      observational study. All participants completed PCOSQ, Beck Depression Inventory,
      Hospital Anxiety and Depression Scale and General Health Questionnaire. Serum
      androgens, fasting insulin, fasting and postload glucose values during an oral
      glucose tolerance test were measured. Changes in these variables and the scores
      of questionnaires were evaluated after 6 months of treatment with EE/DRSP (3
      mg/30 MUg). PARTICIPANTS AND SETTING: Thirty-six patients with PCOS without a
      previous psychiatric diagnosis were included in the study. MAIN RESULTS AND THE
      ROLE OF CHANCE: The main complaints of the patients were hirsutism and irregular
      menses. Accordingly, menstrual and hirsutism problems were the most serious
      concerns followed by emotional problems on the PCOSQ. Eight patients (22.2%) had
      clinical depression scores. After treatment, regular menstrual cycles were
      attained and hirsutism was significantly improved in all patients. Hirsutism and
      emotion domains of the PCOSQ improved at 6 months (P< 0.05 for both). Depression
      was improved in five of eight depressive patients and four new patients showed
      increased depression scores. Overall, depression, anxiety mean scores and
      depression rates did not show a significant change. BIAS, CONFOUNDING AND OTHER
      REASONS FOR CAUTION: The study is subject to the strengths and limitations of
      observational study design. A limitation of our study is the small sample size
      and lack of data related to possible confounding factors. GENERALIZABILITY TO
      OTHER POPULATIONS: Generalizable to Caucasian PCOS.

PMID- 22473395
TI  - The value of anti-Mullerian hormone measurement in the long GnRH agonist
      protocol: association with ovarian response and gonadotrophin-dose adjustments.
AB  - BACKGROUND: This study evaluated the predictive value of serum and follicular
      fluid (FF) concentrations of anti-Mullerian hormone (AMH) with respect to
      treatment outcome variables in an IVF cycle. METHODS: A retrospective analysis
      was performed with data from 731 normogonadotrophic women undergoing controlled
      ovarian stimulation after stimulation with highly purified menotrophin (HP-hMG)
      or rFSH following a long GnRH agonist protocol. RESULTS: In both treatment
      groups, the serum AMH concentration at the start of the stimulation was
      significantly (P < 0.001) positively correlated with the serum levels of
      estradiol (HP-hMG: r = 0.45; rFSH: r = 0.55), androstenedione (HP-hMG: r = 0.50;
      rFSH: 0.49) and total testosterone (HP-hMG: r = 0.40; rFSH: r = 0.36) at the end
      of the stimulation as well as the number of oocytes retrieved (HP-hMG: r = 0.48;
      rFSH: r = 0.62), the AMH concentration in FF (HP-hMG: r = 0.55; rFSH: 0.61) and
      the serum progesterone concentration (HP-hMG: r = 0.39; rFSH: r = 0.50) at oocyte
      retrieval. For both treatments, serum AMH at the start of the stimulation was a
      good predictor of the need to increase or decrease the gonadotrophin dose on
      stimulation day 6 and of ovarian response below (<7 oocytes) or above (>15
      oocytes) the target. No significant relationships were observed between serum AMH
      and embryo quality or ongoing pregnancy. CONCLUSION: The serum AMH concentration
      at the start of the stimulation in IVF patients down-regulated with GnRH agonist
      in the long protocol revealed a positive relationship with ovarian response to
      gonadotrophins in terms of oocytes retrieved and accompanying endocrine response.
      AMH is a good predictor of the need for gonadotrophin-dose adjustment on
      stimulation day 6 for patients with a fixed starting dose, but a poor predictor
      of embryo quality and pregnancy chances in individual patients.

PMID- 22473396
TI  - Parental infertility, infertility treatment and hepatoblastoma: a report from the
      Children's Oncology Group.
AB  - BACKGROUND: A recent study suggested a markedly increased risk of hepatoblastoma
      (HB) among children conceived with treatment for infertility. However, it is not
      clear whether this finding is confounded by the association between HB and low
      birthweight (LBW). METHODS: Associations between parental infertility and its
      treatment and HB were examined using data from a case-control study conducted
      through the Children's Oncology Group (COG). Telephone interviews were completed
      for 383 mothers of cases diagnosed with HB at US COG institutions between January
      2000 and December 2008 and for 387 mothers of controls recruited through state
      birth registries. Logistic regression was used to examine possible associations.
      RESULTS: After adjusting for birthweight and other potential confounders, no
      significant association was found for any of the measures of parental infertility
      or its treatment. In HB cases conceived through assisted reproductive technology
      (ART), 4 of 16 also had Beckwith-Wiedemann syndrome (BWS) compared with 9 of 365
      in HB cases without ART. CONCLUSIONS: Little evidence of an association between
      parental infertility or its treatment and HB was found. The relationship found in
      a previous study could be due to LBW and BWS which are risk factors for HB and
      also associated with parental infertility and its treatment.

PMID- 22473397
TI  - Strong family history of uterine leiomyomatosis warrants fumarate hydratase
      mutation screening.
AB  - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition
      syndrome characterized by cutaneous and uterine leiomyomas and renal cell cancer.
      HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH)
      gene. A Finnish family with nine closely related women with uterine leiomyomas
      was detected by an alert gynecologist. No cutaneous or renal cell tumors were
      reported in the family when it was referred to genetic analyses. Samples were
      available from seven patients, and a novel germline FH mutation was detected in
      five of them. Mutation carriers were symptomatic, had multiple tumors and were
      diagnosed at an early age. This study emphasizes the importance of considering FH
      mutation screening when gynecologists encounter families with multiple severe
      uterine leiomyoma cases. Due to possibility of phenocopies more than one patient
      should be tested. Early mutation detection allows regular screening of the
      mutation carriers and enables early detection of possible highly aggressive renal
      tumors. It may also affect family planning as multiple myomas at early age may
      significantly reduce fertility.

PMID- 22473398
TI  - The Bologna criteria for poor ovarian response; has the job been accomplished?

PMID- 22473399
TI  - Gender differences in drinking patterns and alcohol-related problems in a
      community sample in Sao Paulo, Brazil.
AB  - OBJECTIVE: To investigate drinking patterns and gender differences in alcohol
      related problems in a Brazilian population, with an emphasis on the frequency of
      heavy drinking. METHODS: A cross-sectional study was conducted with a probability
      adult household sample (n = 1,464) in the city of Sao Paulo, Brazil. Alcohol
      intake and ICD-10 psychopathology diagnoses were assessed with the Composite
      International Diagnostic Interview 1.1. The analyses focused on the prevalence
      and determinants of 12-month non-heavy drinking, heavy episodic drinking (4-5
      drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3
      times/week), as well as associated alcohol-related problems according to drinking
      patterns and gender. RESULTS: Nearly 22% (32.4% women, 8.7% men) of the subjects
      were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy
      drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest
      frequency of heavy drinking reported the most problems. Among subjects who did
      not engage in heavy drinking, men reported more problems than did women. A gender
      convergence in the amount of problems was observed when considering heavy
      drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers
      to present lifetime depressive disorders. Lifetime nicotine dependence was
      associated with all drinking patterns. Heavy and frequent drinking was not
      restricted to young ages. CONCLUSIONS: Heavy and frequent episodic drinking was
      strongly associated with problems in a community sample from the largest city in
      Latin America. Prevention policies should target this drinking pattern,
      independent of age or gender. These findings warrant continued research on risky
      drinking behavior, particularly among persistent heavy drinkers at the non
      dependent level.

PMID- 22473400
TI  - Postmortem diagnosis of acute myocardial infarction in patients with acute
      respiratory failure: demographics, etiologic and pulmonary histologic analysis.
AB  - OBJECTIVES: Acute respiratory failure is present in 5% of patients with acute
      myocardial infarction and is responsible for 20% to 30% of the fatal post-acute
      myocardial infarction. The role of inflammation associated with pulmonary edema
      as a cause of acute respiratory failure post-acute myocardial infarction remains
      to be determined. We aimed to describe the demographics, etiologic data and
      histological pulmonary findings obtained through autopsies of patients who died
      during the period from 1990 to 2008 due to acute respiratory failure with no
      diagnosis of acute myocardial infarction during life. METHODS: This study
      considers 4,223 autopsies of patients who died of acute respiratory failure that
      was not preceded by any particular diagnosis while they were alive. The diagnosis
      of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex
      and major associated diseases were recorded for each patient. Pulmonary
      histopathology was categorized as follows: diffuse alveolar damage, pulmonary
      edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds
      ratio of acute myocardial infarction associated with specific histopathology was
      determined by logistic regression. RESULTS: In total, 147 men were included in
      the study. The mean age at the time of death was 64 years. Pulmonary
      histopathology revealed pulmonary edema as well as the presence of diffuse
      alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in
      11.9% of patients, systemic arterial hypertension in 10.1% and dilated
      cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant
      positive association between acute myocardial infarction with diffuse alveolar
      damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that
      in autopsies of patients with acute respiratory failure as the cause of death, 5%
      were diagnosed with acute myocardial infarction. Pulmonary histology revealed a
      significant inflammatory response, which has not previously been reported.

PMID- 22473401
TI  - Metabolic syndrome in patients with chronic hepatitis C virus genotype 1
      infection who do not have obesity or type 2 diabetes.
AB  - OBJECTIVE: The individual components of metabolic syndrome may be independent
      predictors of mortality in patients with liver disease. We aimed to evaluate the
      prevalence of metabolic syndrome and its related components in hepatitis C virus
      infected patients who are not obese and do not have type 2 diabetes. METHODS:
      This cross-sectional study included 125 patients infected with hepatitis C virus
      genotype 1. Metabolic syndrome was defined according to the International
      Diabetes Federation. Anthropometric data were measured according to standardized
      procedures. Bioimpedance analysis was performed on all patients. RESULTS:
      Metabolic syndrome was diagnosed in 21.6% of patients. Of the subjects with
      metabolic syndrome, 59.3% had hypertension, 77.8% had insulin resistance, 85.2%
      were overweight, 48.1% had a high waist circumference, 85.2% had an increased
      body fat percentage, and 92.3% had an elevated waist:hip ratio. In the bivariate
      analysis, female sex (OR 2.58; 95% CI: 1.09-6.25), elevated gamma-glutamyl
      transferase (gammaGT) (OR 2.63; 95% CI: 1.04-7.29), elevated fasting glucose (OR
      8.05; 95% CI: 3.17-21.32), low HDL cholesterol (OR 2.80; 95% CI: 1.07-7.16),
      hypertriglyceridemia (OR 7.91; 95% CI: 2.88-22.71), elevated waist circumference
      (OR 10.33; 95% CI: 3.72-30.67), overweight (OR 11.33; 95% CI: 3.97-41.07), and
      increased body fat percentage (OR 8.34; 95% CI: 2.94-30.08) were independent
      determinants of metabolic syndrome. Using the final multivariate regression
      model, similar results were observed for abdominal fat (OR 9.98; 95% CI: 2.63
      44.41) and total body fat percentage (OR 8.73; 95% CI: 2.33-42.34). However,
      metabolic syndrome risk was also high for those with blood glucose >5.55 mmol/L
      or HDL cholesterol <0.9 mmol/L (OR 16.69; 95% CI: 4.64-76.35; OR 7.23; 95% CI:
      1.86-32.63, respectively). CONCLUSION: Metabolic syndrome is highly prevalent
      among hepatitis C virus-infected patients without type 2 diabetes or obesity.
      Metabolic syndrome was significantly associated with hypertension, insulin
      resistance, increased abdominal fat, and overweight.

PMID- 22473402
TI  - Applying the new concept of maternal near-miss in an intensive care unit.
AB  - OBJECTIVES: The World Health Organization has recommended investigating near
      misses as a benchmark practice for monitoring maternal healthcare and has
      standardized the criteria for diagnosis. We aimed to study maternal morbidity and
      mortality among women admitted to a general intensive care unit during pregnancy
      or in the postpartum period, using the new World Health Organization criteria.
      METHODS: In a cross-sectional study, 158 cases of severe maternal morbidity were
      classified according to their outcomes: death, maternal near-miss, and
      potentially life-threatening conditions. The health indicators for obstetrical
      care were calculated. A bivariate analysis was performed using the Chi-square
      test with Yate's correction or Fisher's exact test. A multiple regression
      analysis was used to calculate the crude and adjusted odds ratios, together with
      their respective 95% confidence intervals. RESULTS: Among the 158 admissions, 5
      deaths, 43 cases of maternal near-miss, and 110 cases of potentially life
      threatening conditions occurred. The near-miss rate was 4.4 cases per 1,000 live
      births. The near-miss/death ratio was 8.6 near-misses for each maternal death,
      and the overall mortality index was 10.4%. Hypertensive syndromes were the main
      cause of admission (67.7% of the cases, 107/158); however, hemorrhage, mainly due
      to uterine atony and ectopic pregnancy complications, was the main cause of
      maternal near-misses and deaths (17/43 cases of near-miss and 2/5 deaths).
      CONCLUSIONS: Hypertension was the main cause of admission and of potentially life
      threatening conditions; however, hemorrhage was the main cause of maternal near
      misses and deaths at this institution, suggesting that delays may occur in
      implementing appropriate obstetrical care.

PMID- 22473403
TI  - Wilson's disease: an analysis of 28 Brazilian children.
AB  - OBJECTIVES: Clinical-laboratory and evolutionary analysis of twenty-eight
      patients with Wilson's disease. METHODS: Twenty-eight children (twelve females
      and sixteen males) with Wilson's disease were evaluated retrospectively between
      1987 and 2009, with a follow-up of 72 months (1 - 240 months). The clinical,
      laboratory, and histologic features at diagnosis were recorded at the end of the
      study. RESULTS: The median age at diagnosis was 11 years (2 - 18 years). Twelve
      patients were asymptomatic, seven had hepatitis symptoms, five had raised
      aminotransferase levels, three had hepatomegaly associated with neurological
      disorders, one had fulminant hepatitis with hemolytic anemia, and six patients
      presented with a Kayser-Fleischer ring. A histological analysis revealed that six
      children had chronic hepatitis, seven had cirrhosis, two had steatosis, one had
      portal fibrosis, and one had massive necrosis. The treatment consisted of D
      penicillamine associated with pyridoxine for 26 patients. Adverse effects were
      observed in the other two patients: one presented with uncontrollable vomiting
      and the other demonstrated elastosis perforans serpiginosa. At the end of the
      study, all 26 treated patients were asymptomatic. Twenty-four of the patients
      were treated with D-penicillamine and pyridoxine, and two were treated with
      trientine and zinc sulfate. A liver transplant was performed in one patient with
      fulminant hepatitis, but the final patient died 48 hours after admission to the
      intensive care unit. CONCLUSIONS: Family screenings associated with early
      treatment are important in preventing Wilson's disease symptoms and potentially
      fatal disease progression. The study suggests that Wilson's disease must be ruled
      out in children older than two years presenting with abnormal levels of hepatic
      enzymes because of the heterogeneity of symptoms and the encouraging treatment
      results obtained so far.

PMID- 22473404
TI  - Isolated limb perfusion with hyperthermia and chemotherapy: predictive factors
      for regional toxicity.
AB  - OBJECTIVE: Isolated limb perfusion combined with melphalan is an accepted
      treatment for obtaining locoregional control in advanced melanoma of the
      extremities and other malignant neoplasias restricted to the limb. This study
      aims to examine the factors associated with toxicity caused by the regional
      method. We considered the technical aspects of severe complications associated
      with the procedure in an attempt to diminish the patient morbidity that occurs
      during the learning curve. METHODS: We conducted a retrospective analysis of the
      records of patients who underwent perfusion at the AC Camargo Hospital in Sao
      Paulo, Brazil between January 2000 and January 2009. The Wieberdink scale was
      applied to classify local toxicity and its relation to clinical and laboratory
      variables. RESULTS: Fifty-eight perfusions were performed in 55 patients. Most
      patients (86.2%) presented a toxicity level between I and III. Grade V toxicity
      was seen in five cases (8.6%), four of which occurred in the first 2 years.
      Creatine phosphokinase, an important predictive factor for toxicity, had an
      average value of 231.8 for toxicity grades I-III and 1286.2 for toxicity grades
      IV-V (p = 0.001). There was a relationship between the melphalan dose and
      toxicity, which was 77 mg (25 to 130 mg) for toxicity grades I-II and 93.5 mg (45
      to 120 mg) for toxicity grades IV-V (p = 0.0204). CONCLUSION: It is possible to
      prevent the toxicity associated with melphalan by adjusting the dose according to
      the patient's body weight (especially for women and obese patients) and the
      creatine phosphokinase values in the postoperative period.

PMID- 22473405
TI  - Evaluation of serial C-reactive protein measurements after surgical treatment of
      pleural empyema.
AB  - OBJECTIVE: Serial C-reactive protein measurements have been used to diagnose and
      monitor the response to therapy in patients with pneumonia and other infectious
      diseases. Nonetheless, the role of C-reactive protein measurement after surgical
      treatment for pleural empyema is not well defined. The aim of this study is to
      describe the behavior of C-reactive protein levels after the surgical treatment
      of pleural empyema and to correlate this parameter with the patient's prognosis.
      METHODS: We retrospectively analyzed the records of patients with pleural empyema
      treated by either chest-tube drainage or surgery from January 2006 to December
      2008. C-reactive protein levels were recorded preoperatively and 2 and 7 days
      postoperatively. The clinical outcome was binary: success or failure (mortality
      or the need for repeated pleural intervention). RESULTS: The study group
      comprised fifty-two patients. The median C-reactive protein values were as
      follows: 146 mg/L (pre-operative), 134 mg/L (post-operative day 2), and 116 mg/L
      (post-operative day 7). There was a trend toward a decrease in these values
      during the first week after surgery, but this difference was only statistically
      significant on day 7 after surgery. Over the first week after surgery, the C
      reactive protein values decreased similarly in both groups (successful and failed
      treatment). No correlation between the preoperative C-reactive protein level and
      the clinical outcome was found. CONCLUSIONS: We observed that, in contrast to
      other medical conditions, C-reactive protein levels fall slowly during the first
      postoperative week in patients who have undergone surgical treatment for pleural
      empyema. No correlation between the perioperative C-reactive protein level and
      the clinical outcome was observed.

PMID- 22473406
TI  - Prevalence of eye disease in Brazilian patients with psoriatic arthritis.
AB  - OBJECTIVES: The aim of this study was to report the type and frequency of ocular
      manifestations in Brazilian psoriatic arthritis patients. METHODS: We conducted a
      cross-sectional study in a Brazilian tertiary hospital. The test group included
      40 patients who had psoriatic arthritis according to the Classification Criteria
      for Psoriatic Arthritis. A control group of 40 individuals was matched for age
      and gender. All of the patients underwent ophthalmic evaluation, which included
      best-corrected visual acuity, slit lamp and fundus examinations, and dry eye
      diagnostic tests (Schirmer I, tear breakup time and rose bengal). Demographic
      parameters were also evaluated. RESULTS: The mean age of the patients was 53.9+/
      13.1 years; the mean disease duration was 8+/-10.5 years. Most of the patients
      were women (60%), and the majority had polyarticular disease (57.5%). Several
      ocular abnormalities were found, including punctate keratitis, pinguecula,
      blepharitis, pterygium, cataract, glaucoma, uveitis, and retinal microvascular
      abnormalities. There were no significant differences in the rates of these
      abnormalities compared with the control group, however. The Keratoconjunctivitis
      sicca and dry eye diagnostic tests were more often positive in the patients with
      psoriatic arthritis than in the control group. CONCLUSIONS: In this study,
      keratoconjunctivitis sicca was the most common ocular finding related to
      psoriatic arthritis. Therefore, we recommend early ophthalmologic evaluations for
      all psoriatic arthritis patients who complain of eye symptoms.

PMID- 22473407
TI  - Isolated total RNA and protein are preserved after thawing for more than twenty
      four hours.
AB  - OBJECTIVE: The preservation of biological samples at a low temperature is
      important for later biochemical and/or histological analyses. However, the
      molecular viability of thawed samples has not been studied sufficiently in depth.
      The present study was undertaken to evaluate the viability of intact tissues,
      tissue homogenates, and isolated total RNA after defrosting for more than twenty
      four hours. METHODS: The molecular viability of the thawed samples (n = 82) was
      assessed using the A260/A280 ratio, the RNA concentration, the RNA integrity, the
      level of intact mRNA determined by reverse transcriptase polymerase chain
      reaction, the protein level determined by Western blotting, and an examination of
      the histological structure. RESULTS: The integrity of the total RNA was not
      preserved in the thawed intact tissue, but the RNA integrity and level of mRNA
      were perfectly preserved in isolated defrosted samples of total RNA.
      Additionally, the level of beta-actin protein was preserved in both thawed intact
      tissue and homogenates. CONCLUSION: Isolated total RNA does not undergo
      degradation due to thawing for at least 24 hours, and it is recommended to
      isolate the total RNA as soon as possible after tissue collection. Moreover, the
      protein level is preserved in defrosted tissues.

PMID- 22473408
TI  - Reporting on health-related research in two prestigious Brazilian newspapers.
AB  - OBJECTIVES: The dissemination of health-related news through newspapers can
      influence the behavior of patients and of health care providers. We conducted a
      study to analyze the characteristics of health-related research published by two
      leading Brazilian newspapers. METHOD: We retrospectively evaluated health-related
      news published in the electronic versions of the newspapers Folha de Sao Paulo
      and O Estado de Sao Paulo over a period of three months (July through September,
      2009). Only articles mentioning medical research were included. The articles were
      categorized according to topic, source, study location and the nature of the
      headline. We also analyzed the presence of background information on the topic,
      citations of medical periodicals, national contextualization and references to
      products or companies. RESULTS: Scientific research articles corresponded to 57%
      and 20% of health-related articles published by Folha de Sao Paulo and O Estado
      de Sao Paulo, respectively. Folha de Sao Paulo published significantly more
      articles about national studies, and most articles were written by its own staff.
      In contrast, most articles in O Estado de Sao Paulo came from news agencies.
      Folha de Sao Paulo also better contextualized its reports for Brazilian society.
      O Estado de Sao Paulo tended to cite the name of the periodical in which the
      study was published more frequently, but their articles lacked national
      contextualization. CONCLUSION: The results showed a significant difference in the
      way in which the studied newspapers report on health-related research. Folha de
      Sao Paulo tends to write its own articles and more frequently publishes the
      results of national research, whereas O Estado de Sao Paulo publishes articles
      that originate in news agencies, most of which have little national
      contextualization.

PMID- 22473409
TI  - Growth hormone response to growth hormone-releasing peptide-2 in growth hormone
      deficient little mice.
AB  - OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone
      independent action of a growth hormone secretagogue, GHRP-2, in pituitary
      somatotroph cells in the presence of inactive growth hormone-releasing hormone
      receptors. MATERIALS AND METHODS: The responses of serum growth hormone to
      acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a
      model of GH deficiency arising from mutated growth hormone-releasing hormone
      receptors, were compared to those observed in the heterozygous (lit/+)
      littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration
      of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone
      release of 9.3+/-1.5 ng/ml was observed compared with 1.04+/-1.15 ng/ml in
      controls (p<0.001). In comparison, an intermediate growth hormone release of
      34.5+/-9.7 ng/ml and a higher growth hormone release of 163+/-46 ng/ml were
      induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2
      stimulated growth hormone in the lit/lit mice, and the release of growth hormone
      in vivo may be only partially dependent on growth hormone-releasing hormone.
      Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit
      mice under basal and stimulated conditions. CONCLUSIONS: Here, we have
      demonstrated that lit/lit mice, which harbor a germline mutation in the Growth
      hormone-releasing hormone gene, maintain a limited but statistically significant
      growth hormone elevation after exogenous stimulation with GHRP-2. The present
      data probably reflect a direct, growth hormone-independent effect on Growth
      hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little
      mice that is mediated by growth hormone S-R 1a.

PMID- 22473410
TI  - Endothelial function in pre-pubertal children at risk of developing
      cardiomyopathy: a new frontier.
AB  - Although it is known that obesity, diabetes, and Kawasaki's disease play
      important roles in systemic inflammation and in the development of both
      endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the
      endothelial function of pre-pubertal children suffering from cardiomyopathy. In
      this study, we performed a systematic review of the literature on pre-pubertal
      children at risk of developing cardiomyopathy to assess the endothelial function
      of pre-pubertal children at risk of developing cardiomyopathy. We searched the
      published literature indexed in PubMed, Bireme and SciELO using the keywords
      'endothelial', 'children', 'pediatric' and 'infant' and then compiled a
      systematic review. The end points were age, the pubertal stage, sex differences,
      the method used for the endothelial evaluation and the endothelial values
      themselves. No studies on children with cardiomyopathy were found. Only 11 papers
      were selected for our complete analysis, where these included reports on the flow
      mediated percentage dilatation, the values of which were 9.80+/-1.80, 5.90+/
      1.29, 4.50+/-0.70, and 7.10+/-1.27 for healthy, obese, diabetic and pre-pubertal
      children with Kawasaki's disease, respectively. There was no significant
      difference in the dilatation, independent of the endothelium, either among the
      groups or between the genders for both of the measurements in children; similar
      results have been found in adolescents and adults. The endothelial function in
      cardiomyopathic children remains unclear because of the lack of data;
      nevertheless, the known dysfunctions in children with obesity, type 1 diabetes
      and Kawasaki's disease may influence the severity of the cardiovascular symptoms,
      the prognosis, and the mortality rate. The results of this study encourage future
      research into the consequences of endothelial dysfunction in pre-pubertal
      children.

PMID- 22473411
TI  - Surgery with intraoperative botulinum toxin-A injection for the treatment of
      large-angle horizontal strabismus: a pilot study.

PMID- 22473412
TI  - Assessing the benefits of rosiglitazone in women with polycystic ovary syndrome
      through its effects on insulin-like growth factor 1, insulin-like growth factor
      binding protein-3 and insulin resistance: a pilot study.

PMID- 22473413
TI  - Evaluation of bacterial infections in organ transplantation.

PMID- 22473414
TI  - Sclerosing mesenteritis as an unusual cause of fever of unknown origin: a case
      report and review.

PMID- 22473415
TI  - Poststernotomy aspergillosis: successful treatment with voriconazole, surgical
      debridement and vacuum-assisted closure therapy.

PMID- 22473416
TI  - Relationship between polypyrrole morphology and electrochemical activity towards
      oxygen reduction reaction.
AB  - The relationship between the morphology of polypyrrole and their electrocatalytic
      performances towards the oxygen reduction reaction (ORR) in alkaline media is
      described; annealed polypyrrole with granular- and tubules-like morphology
      exhibited different catalytic efficiencies.

PMID- 22473417
TI  - Control the size and surface chemistry of graphene for the rising fluorescent
      materials.
AB  - Fluorescent graphene-based materials, labelled as a sort of fluorescent carbon
      based nanomaterial, have drawn increasing attention in recent years. When the
      size and structure of graphene were controlled properly, photoluminescence was
      induced in graphene, resulting in the so-called fluorescent graphene (FG). FG has
      a size-, defect-, and wavelength-dependent luminescence emission, which is
      similar to traditional semiconductor-based quantum dots. Moreover, with excellent
      chemical stability, fine biocompatibility, low toxicity, up-conversion emission,
      pH-sensitivity and resistance to photobleaching, FG promises to offer substantial
      applications in numerous areas: bioimaging, photovoltaics, sensors, etc.
      Currently, research works have allowed FG to be produced by many approaches
      ranging from simple oxidation of graphene to cutting carbon sources and organic
      synthesis from small molecules. In this Feature Article, we summarize the
      reported fluorescent graphenes, with emphasis on their category, properties,
      synthesis and applications. Meanwhile, we give a perspective on their subsequent
      developments and compare the features of FG and other fluorescent carbon-based
      materials.

PMID- 22473418
TI  - Tasman Spirit oil spill in Pakistan: research response and lessons learned.
AB  - BACKGROUND: This article presents lessons learned from an investigation of the
      acute human health effects of the "Tasman Spirit" oil spill from a perspective of
      conducting rapid response investigations in developing countries. METHODS: We
      reviewed various steps in our investigation, other studies on oil spills in
      Pakistan and around the world, and reflected upon our discussions and
      interactions with various stakeholders. RESULTS: The article highlights the
      importance of applying a public health, legal, and ethical framework for
      conducting rapid response investigations, developing a pre-established funding
      mechanism, and addressing study design issues, exposure and outcome measurements,
      political issues, community engagement, and communication of results. CONCLUSION:
      There is need to develop ethical and legal framework and funding mechanism for
      conducting rapid response research in developing countries. A repository of study
      protocols, validated tools, and laboratory methods for exposure and outcome
      assessment would be greatly beneficial.

PMID- 22473419
TI  - Detection of invasive pulmonary aspergillosis in haematological malignancy
      patients by using lateral-flow technology.
AB  - Invasive pulmonary aspergillosis (IPA) is a leading cause of morbidity and
      mortality in haematological malignancy patients and hematopoietic stem cell
      transplant recipients(1). Detection of IPA represents a formidable diagnostic
      challenge and, in the absence of a 'gold standard', relies on a combination of
      clinical data and microbiology and histopathology where feasible. Diagnosis of
      IPA must conform to the European Organization for Research and Treatment of
      Cancer and the National Institute of Allergy and Infectious Diseases Mycology
      Study Group (EORTC/MSG) consensus defining "proven", "probable", and "possible"
      invasive fungal diseases(2). Currently, no nucleic acid-based tests have been
      externally validated for IPA detection and so polymerase chain reaction (PCR) is
      not included in current EORTC/MSG diagnostic criteria.    Identification of
      Aspergillus in histological sections is problematic because of similarities in
      hyphal morphologies with other invasive fungal pathogens(3), and proven
      identification requires isolation of the etiologic agent in pure culture. Culture
      based approaches rely on the availability of biopsy samples, but these are not
      always accessible in sick patients, and do not always yield viable propagules for
      culture when obtained.    An important feature in the pathogenesis of Aspergillus
      is angio-invasion, a trait that provides opportunities to track the fungus
      immunologically using tests that detect characteristic antigenic signatures
      molecules in serum and bronchoalveolar lavage (BAL) fluids. This has led to the
      development of the Platelia enzyme immunoassay (GM-EIA) that detects Aspergillus
      galactomannan and a 'pan-fungal' assay (Fungitell test) that detects the
      conserved fungal cell wall component (1 ->3)-beta-D-glucan, but not in the
      mucorales that lack this component in their cell walls(1,4). Issues surrounding
      the accuracy of these tests(1,4-6) has led to the recent development of next
      generation monoclonal antibody (MAb)-based assays that detect surrogate markers
      of infection(1,5).    Thornton(5) recently described the generation of an
      Aspergillus-specific MAb (JF5) using hybridoma technology and its use to develop
      an immuno-chromatographic lateral-flow device (LFD) for the point-of-care (POC)
      diagnosis of IPA. A major advantage of the LFD is its ability to detect activity
      since MAb JF5 binds to an extracellular glycoprotein antigen that is secreted
      during active growth of the fungus only(5). This is an important consideration
      when using fluids such as lung BAL for diagnosing IPA since Aspergillus spores
      are a common component of inhaled air. The utility of the device in diagnosing
      IPA has been demonstrated using an animal model of infection, where the LFD
      displayed improved sensitivity and specificity compared to the Platelia GM and
      Fungitell (1 -> 3)-beta-D-glucan assays(7).    Here, we present a simple LFD
      procedure to detect Aspergillus antigen in human serum and BAL fluids. Its speed
      and accuracy provides a novel adjunct point-of-care test for diagnosis of IPA in
      haematological malignancy patients.

PMID- 22473420
TI  - A population-based prospective 24-month study of stroke: incidence and 30-day
      case-fatality rates of first-ever strokes in Croatia.
AB  - BACKGROUND: In Central/Eastern European countries, cerebrovascular diseases are
      among the leading causes of mortality. We aimed to determine the incidence of
      first-ever stroke (FES) in the north-western part of Croatia. METHODS: A
      population-based prospective incidence study was conducted between July 1, 2007,
      and June 30, 2009. Cases were sought from multiple overlapping sources. Incidence
      rates by stroke type and gender were calculated. RESULTS: A total of 1,487 events
      were recorded, 1,017 of which were FESs. European age-adjusted incidence rates
      (per 100,000 population) were: total FESs 223.6 [women/men rate ratio (w/m RR) =
      0.65 (95% CI 0.57-0.73)]; ischemic stroke 162.4 (w/m RR = 0.65, 0.56-0.76);
      intracerebral hemorrhage 28.4 (w/m RR = 0.44, 0.30-0.63); subarachnoid hemorrhage
      7.2 (w/m RR = 1.18, 0.55-2.54); unknown etiology 25.5 (w/m RR = 0.78, 0.54-1.14).
      Adjusted incidence rates of ischemic strokes by subtype were: cardioembolic 52.9
      (w/m RR = 0.77, 0.59-0.99); large-artery atherosclerosis 14.4 (w/m RR = 0.22,
      0.13-0.38); small-artery occlusion 24.5 (w/m RR = 0.53, 0.37-0.77) and 'other or
      uncertain causes' 70.6 (w/m RR = 0.77, 0.62-0.97). Thirty-day case-fatality rate
      was 23.5% overall and 17.1% for ischemic stroke. CONCLUSIONS: The incidence of
      FES and 30-day mortality of patients with ischemic strokes in the studied
      population is higher than in Western European countries.

PMID- 22473421
TI  - Chiral cyclopalladated complex promoted asymmetric synthesis of diester
      substituted P,N-ligands via stepwise hydrophosphination and hydroamination
      reactions.
AB  - A series of enantiomerically pure 1,2-diester substituted P,N-ligands
      incorporating two chiral carbons in the backbone were generated in high yields
      and high stereoselectivity from acetylenedicarboxylate via initial
      hydrophosphination using diphenylphosphine followed by hydroamination with
      various primary and secondary amines. The reactions were activated and
      stereochemically controlled by the organopalladium complex containing ortho
      palladated (S)-(1-(dimethylamino)ethyl)naphthalene under mild conditions. The
      absolute stereochemistry and the coordination chemistry of P,N-products were
      determined by the single crystal X-ray diffraction analysis. All the chiral P,N
      ligands could be liberated from the palladium template without loss of optical
      purity. Subsequent recomplexation to selected chiral palladium centers confirmed
      the optical purity of the new functionalized chiral P,N-ligands.

PMID- 22473422
TI  - Synthesis and in vitro anti-tubercular evaluation of 1,2,3-triazole tethered beta
      lactam-ferrocene and beta-lactam-ferrocenylchalcone chimeric scaffolds.
AB  - Twenty different triazoles were prepared to probe the anti-tubercular structure
      activity relationships (SAR) within the beta-lactam-ferrocene-triazole conjugate
      family. The compounds have been synthesized by copper-catalyzed "click
      chemistry". In vitro anti-tubercular activity was determined for each compound
      but the synthesized hybrids failed to inhibit Mycobacterium tuberculosis growth
      even at high doses. The manuscript assumes significance as this is the first
      report on the inclusion of ferrocene nucleus in the well established beta-lactam
      family via triazole linkers with reputed physicochemical profiles.

PMID- 22473423
TI  - Involvement of physician extenders in ambulatory otolaryngology practice.
AB  - OBJECTIVES/HYPOTHESIS: Determine the penetration and point-of-care patterns for
      physician extenders in ambulatory otolaryngology practice. STUDY DESIGN: Cross
      sectional analysis of national database. METHODS: The National Ambulatory Medical
      Care Survey was examined for 2008 and 2009, extracting all cases of ambulatory
      visits to an otolaryngology outpatient setting. Visit types were then segregated
      according to providers seen including physician, advanced practice clinicians
      (APCs) (nurse practitioner and/or physician assistant) and nurses. Visit types
      were determined (physician alone, physician with APC, or APC alone) as well as
      type of patient seen (new vs. established patient). The top 10 diagnoses were
      compiled according to provider visit type. RESULTS: An estimated 38.6 +/- 3.7
      million outpatient office otolaryngology visits were studied. An APC was seen in
      6.3 +/- 2.0% of visits (physician assistant, 4.6 +/- 1.9% visits; nurse
      practitioner, 1.7 +/- 0.9% of visits), and a nurse was involved in 25.1 +/- 7.6%
      of visits. Nurse practitioners were more likely see patients independently
      (47.7%) than were physician assistants (23.3%). APCs were more likely to be
      involved with established patient visits (7.2 +/- 2.3%) rather than new patient
      visits (4.3 +/- 1.8%, P = .08). Disorders of the external and middle ears were
      the most common diagnoses seen by APCs. CONCLUSIONS: Although APCs are expected
      to expand numbers in otolaryngology, contemporary data indicate that current
      penetration of APCs into ambulatory otolaryngology care remains relatively
      limited. These data provide an initial assessment for future modeling of APCs and
      otolaryngologic care.

PMID- 22473425
TI  - [New international activities in psychosomatic medicine].

PMID- 22473424
TI  - Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer
      axons during pathfinding in the developing rat forebrain.
AB  - Precise axon pathfinding is crucial for establishment of the initial neuronal
      network during development. Pioneer axons navigate without the help of
      preexisting axons and pave the way for follower axons that project later. Voltage
      gated ion channels make up the intrinsic electrical activity of pioneer axons and
      regulate axon pathfinding. To elucidate which channel molecules are present in
      pioneer axons, immunohistochemical analysis was performed to examine 14 voltage
      gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2,
      Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat
      forebrain, including the optic nerve, corpus callosum, corticofugal fibers,
      thalamocortical axons, lateral olfactory tract, hippocamposeptal projection,
      anterior commissure, hippocampal commissure, and medial longitudinal fasciculus.
      We found A-type K+ channel Kv3.4 in both pioneer axons and early follower axons
      and L-type Ca2+ channel Cav1.2 in pioneer axons and early and late follower
      axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer
      neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most
      fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in
      most fiber tracts during axon pathfinding but were downregulated beginning in
      synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav
      channels (e.g., Nav1.2) were absent from these fiber tracts (except for the
      corpus callosum) during pathfinding of pioneer axons. These data suggest that
      Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to
      control Ca2+ -dependent electrical activity of pioneer axons and play important
      roles during axon pathfinding.

PMID- 22473426
TI  - [Neurocognitive deficits in patients with malignant brain tumors].
AB  - This article reviews research on neurocognitive deficits in adult patients with
      malignant brain tumors, i. e. high-grade primary brain tumors and brain
      metastases. Brain tumor patients experience significant neurocognitive deficits,
      mainly in the domains of attention, memory, executive function and psychomotor
      function. Neurosurgical, radiotherapeutic or radiochemotherapeutic treatment
      regimens are often associated with a decline in cognitive functioning. However,
      such empirical observations are often confounded with the neurocognitive effects
      of tumor progression. Few studies investigated associations among neurocognitive
      deficits and distress. These studies revealed contradictory results. Similarly,
      research on neurocognitive deficits and health-related quality of life has
      resulted in equivocal evidence. Furthermore, convincing empirical evidence for
      the effectiveness of neurocognitive training in patients with high-grade brain
      tumors is lacking.

PMID- 22473427
TI  - [Genetics, gene-environment-interactions and epigenetics in the development of
      depressive disorders].
AB  - As demonstrated by numerous studies in quantitative and molecular genetics,
      genetic factors play an important role in the development of mental disorders.
      This review gives an overview on the methods and the available evidence from
      research in quantitative and molecular genetics of depressive disorders with a
      special focus on recent approaches, i.e. epigenetic research and gene environment
      interactions (with the example of the serotonin transporter gene 5-HTTLPR). The
      implications of the available evidence are discussed in the context of future
      research as well as of clinical practice.

PMID- 22473428
TI  - [Longer-term outcome of CBT for eating disorders in a naturalistic setting].
AB  - The efficacy of cognitive-behavioral therapy (CBT) for adults with eating
      disorders has been shown in several naturalistic studies. In contrast studies
      showing longer-term effects in naturalistic outpatient treatment are still
      lacking. Therefore 99 female patients with the primary DSM-IV diagnosis of an
      eating disorder were considered in this analysis. Longer-term duration outcome
      data exist for 53,5% (n=53). EDE-Q, BDI and BSI were used as outcome measures and
      were given to patients at the beginning, the end and 18 month after the end of
      treatment. The effect sizes remained fairly steady throughout follow-up. Also the
      response rates remained the same on average (63,6%), whereupon 25% lost their
      status of response and 22,7% showed spontaneous remission during long-term
      evaluation. Although the average longer-term effect sizes of CBT in an outpatient
      routine health-care service were maintained throughout follow-up, one fourth of
      the females developed symptomatology again.

PMID- 22473429
TI  - [Psychological distress of breast cancer patients: screening and patients'
      request for psycho-oncological care as indicators of health-related quality of
      life].
AB  - Health-related quality of life (QoL) in breast cancer patients strongly depends
      on emotional well-being. QoL (EORTC-QLQ-C30), psychological distress (HADS), and
      patient's request for psycho-oncological care were assessed in 103 breast cancer
      patients during initial hospitalization. Clinical diagnoses according to ICD-10-F
      were made by clinical interview. As expected, both positive HADS screens (>13)
      and clinical diagnoses of mental disorders were inversely related to QoL.
      However, in multivariate analysis of variance only positive HADS scores but not
      clinical diagnoses of mental disorders significantly predicted QoL. The
      performance of psychological screening instruments should therefore not only be
      judged by their ability to detect clinical diagnoses but also by their relevance
      for reflecting patients' QoL.

PMID- 22473430
TI  - [Eating disturbances in the German population].
AB  - In a representative German population sample, the prevalence of eating
      disturbances was determined using the Eating Disorder Examination-Questionnaire.
      Overall, 3,9% revealed eating disturbances. In particular, young women and obese
      persons had an increased likelihood of these disturbances, but men and older
      persons were concerned as well. Further research is warranted on eating
      disturbances across the life span, both sexes and weight status.

PMID- 22473431
TI  - [Schema therapy: an integrative approach for personality disorders].
AB  - Schema Therapy (ST) is a comprehensive approach deriving from cognitive
      behavioral therapy (CBT) for the treatment of chronic personality problems. ST
      extends CBT in 3 major issues: 1. The Schema-Mode-Model. 2. The therapeutic
      relationship. 3. The intensive use of experiential techniques. Schemas are
      persistent, rigid, and dysfunctional patterns preventing the patient from further
      personal emotive-interpersonal development. The central focus of the therapeutic
      process is the relationship between the therapist and the patient. Supported by
      the therapeutic relationship the patient gets in touch with painful childhood
      experiences. In ST, the core schemas are identified, put into a biographical
      context, and weakened by using several specific therapeutic techniques including
      experiential methods and strategies taken from Gestalt therapy that enrich
      traditional CBT techniques.

PMID- 22473432
TI  - [Evaluation of treatment effects in quasi-experimental studies].

PMID- 22473433
TI  - Do Alcohol Warning Labels Influence Men's and Women's Attempts to Deter Others
      from Driving When Intoxicated?
AB  - Research on the federally mandated alcohol warning label has found mixed results,
      but some findings are consistent with a modest influence on precautionary
      behaviors to reduce drinkers' self-reported drunk driving. We hypothesized that
      warnings would also influence the likelihood of intervening to deter other's
      driving after drinking. Using data from 1376 adult drinkers in a US national
      survey, a conceptual model reflecting effects of exposure to the label's drunk
      driving message on taking actions to avert another's driving under the influence
      was tested in a structural equation modeling framework. For males and females, in
      structural models with drinking and handling of alcoholic beverages potentially
      affecting both message recall and intervening, the predicted relationships were
      found between message recall and actions to deter another's drinking driving.
      This finding suggests that an important preventive effect of the alcohol warning
      label may be to legitimate collateral's attempts to avert another's drunk
      driving.

PMID- 22473434
TI  - Health care-associated hepatitis C virus infections attributed to narcotic
      diversion.
AB  - BACKGROUND: Three cases of genetically related hepatitis C virus (HCV) infection
      that were unattributable to infection control breaches were identified at a
      health care facility. OBJECTIVE: To investigate HCV transmission from an HCV
      infected health care worker to patients through drug diversion. DESIGN: Cluster
      and look-back investigations. SETTING: Acute care hospital and affiliated
      multispecialty clinic. PATIENTS: Inpatients and outpatients during the period of
      HCV transmission. MEASUREMENTS: Employee work and narcotic dispensing records,
      blood testing for HCV antibody and RNA, and sequencing of the NS5B gene and the
      hypervariable region 1 of the E2 gene. RESULTS: 21 employees were recorded as
      being at work or as retrieving a narcotic from an automated dispensing cabinet in
      an area where a narcotic was administered to each of the 3 case patients; all
      employees provided blood samples for HCV testing. One employee was infected with
      HCV that had more than 95% NS5B sequence homology with the HCV strains of the 3
      case patients. Quasi-species analysis showed close genetic relatedness with
      variants from each of the case patients and more than 97.9% nucleotide identity.
      The employee acknowledged parenteral opiate diversion. An investigation
      identified 6132 patients at risk for exposure to HCV because of the drug
      diversion. Of the 3929 living patients, 3444 (87.7%) were screened for infection.
      Two additional cases of genetically related HCV infection attributable to the
      employee were identified. LIMITATION: Of the living patients at risk for HCV
      exposure, 12.3% were not tested. CONCLUSION: Five cases of HCV infection
      occurring over 3 to 4 years were attributed to drug diversion by an HCV-infected
      health care worker. Studies of drug diversion and assessments of strategies to
      prevent narcotics tampering in all health care settings are needed. PRIMARY
      FUNDING SOURCE: None.

PMID- 22473435
TI  - Effect of an iPod video intervention on consent to donate organs: a randomized
      trial.
AB  - BACKGROUND: The gap between the supply of organs available for transplantation
      and demand is growing, especially among ethnic groups. OBJECTIVE: To evaluate the
      effect of a video designed to address concerns of ethnic groups about organ
      donation. DESIGN: Cluster randomized, controlled trial. Randomization was
      performed by using a random-number table with centralized allocation concealment.
      Participants and investigators assessing outcomes were not blinded to group
      assignment. (ClinicalTrials.gov registration number: NCT00870506) SETTING: Twelve
      branches of the Ohio Bureau of Motor Vehicles in northeastern Ohio. PARTICIPANTS:
      952 participants aged 15 to 66 years. INTERVENTION: Video (intervention; n = 443)
      or usual Bureau of Motor Vehicles license practices (control; n = 509).
      MEASUREMENTS: The primary outcome was the proportion of participants who provided
      consent for organ donation on a newly acquired driver's license, learner's
      permit, or state identification card. Secondary outcomes included willingness to
      make a living kidney donation to a family member in need and personal beliefs
      about donation. RESULTS: More participants who viewed the video consented to
      donate organs than control participants (84% vs. 72%; difference, 12 percentage
      points [95% CI, 6 to 17 percentage points]). The video was effective among black
      participants (76% vs. 54%; difference, 22 percentage points [CI, 9 to 35
      percentage points]) and white participants (88% vs. 77%; difference, 11
      percentage points [CI, 5 to 15 percentage points]). At the end of the trial,
      fewer intervention than control participants reported having insufficient
      information about organ donation (34% vs. 44%; difference, -10 percentage points
      [CI, -16 to -4 percentage points]), wanting to be buried with all of their organs
      (14% vs. 25%; difference, -11 percentage points [CI, -16 to -6 percentage
      points]), and having conflicts with organ donation (7% vs. 11%; difference, -4
      percentage points [CI, -8 to -2 percentage points]). LIMITATION: How the observed
      increases in consent to donate organs might translate into a greater organ supply
      in the region is unclear. CONCLUSION: Exposure to a brief video addressing
      concerns that ethnic groups have about organ donation just before obtaining a
      license, permit, or identification card increased consent to donate organs among
      white and black participants. PRIMARY FUNDING SOURCE: National Institutes of
      Health and the Robert Wood Johnson Foundation.

PMID- 22473436
TI  - Overdiagnosis of invasive breast cancer due to mammography screening: results
      from the Norwegian screening program.
AB  - BACKGROUND: Precise quantification of overdiagnosis of breast cancer (defined as
      the percentage of cases of cancer that would not have become clinically apparent
      in a woman's lifetime without screening) due to mammography screening has been
      hampered by lack of valid comparison groups that identify incidence trends
      attributable to screening versus those due to temporal trends in incidence.
      OBJECTIVE: To estimate the percentage of overdiagnosis of breast cancer
      attributable to mammography screening. DESIGN: Comparison of invasive breast
      cancer incidence with and without screening. SETTING: A nationwide mammography
      screening program in Norway (inviting women aged 50 to 69 years), gradually
      implemented from 1996 to 2005. PARTICIPANTS: The Norwegian female population.
      MEASUREMENTS: Concomitant incidence of invasive breast cancer from 1996 to 2005
      in counties where the screening program was implemented compared with that in
      counties where the program was not yet implemented. To adjust for changes in
      temporal trends in breast cancer incidence, incidence rates during the preceding
      decade were also examined. The percentage of overdiagnosis was calculated by
      accounting for the expected decrease in incidence following cessation of
      screening after age 69 years (approach 1) and by comparing incidence in the
      current screening group with incidence among women 2 and 5 years older in the
      historical screening groups, accounting for average lead time (approach 2).
      RESULTS: A total of 39,888 patients with invasive breast cancer were included,
      7793 of whom were diagnosed after the screening program started. The estimated
      rate of overdiagnosis attributable to the program was 18% to 25% (P < 0.001) for
      approach 1 and 15% to 20% (P < 0.001) for approach 2. Thus, 15% to 25% of cases
      of cancer are overdiagnosed, translating to 6 to 10 women overdiagnosed for every
      2500 women invited. LIMITATION: The study was registry-based. CONCLUSION:
      Mammography screening entails a substantial amount of overdiagnosis. PRIMARY
      FUNDING SOURCE: Norwegian Research Council and Frontier Science.

PMID- 22473437
TI  - Guidelines International Network: toward international standards for clinical
      practice guidelines.
AB  - Guideline development processes vary substantially, and many guidelines do not
      meet basic quality criteria. Standards for guideline development can help
      organizations ensure that recommendations are evidence-based and can help users
      identify high-quality guidelines. Such organizations as the U.S. Institute of
      Medicine and the United Kingdom's National Institute for Health and Clinical
      Excellence have developed recommendations to define trustworthy guidelines within
      their locales. Many groups charged with guideline development find the lengthy
      list of standards developed by such organizations to be aspirational but
      infeasible to follow in entirety. Founded in 2002, the Guidelines International
      Network (G-I-N) is a network of guideline developers that includes 93
      organizations and 89 individual members representing 46 countries. The G-I-N
      board of trustees recognized the importance of guideline development processes
      that are both rigorous and feasible even for modestly funded groups to implement
      and initiated an effort toward consensus about minimum standards for high-quality
      guidelines. In contrast to other existing standards for guideline development at
      national or local levels, the key components proposed by G-I-N will represent the
      consensus of an international, multidisciplinary group of active guideline
      developers. This article presents G-I-N's proposed set of key components for
      guideline development. These key components address panel composition, decision
      making process, conflicts of interest, guideline objective, development methods,
      evidence review, basis of recommendations, ratings of evidence and
      recommendations, guideline review, updating processes, and funding. It is hoped
      that this article promotes discussion and eventual agreement on a set of
      international standards for guideline development.

PMID- 22473438
TI  - Nosocomial hepatitis C: more of a hidden epidemic.

PMID- 22473440
TI  - The conductor.

PMID- 22473439
TI  - Overdiagnosis in breast cancer screening: time to tackle an underappreciated
      harm.

PMID- 22473441
TI  - Screening for prostate cancer.

PMID- 22473442
TI  - Screening for prostate cancer.

PMID- 22473443
TI  - Screening for prostate cancer.

PMID- 22473444
TI  - Summaries for patients: Overdiagnosis of invasive breast cancer with mammography
      screening.

PMID- 22473445
TI  - In the clinic. Eating disorders.
AB  - This issue provides a clinical overview of eating disorders focusing on
      prevention, diagnosis, treatment, practice improvement, and patient information.
      Readers can complete the accompanying CME quiz for 1.5 credits. Only ACP members
      and individual subscribers can access the electronic features of In the Clinic.
      Non-subscribers who wish to access this issue of In the Clinic can elect "Pay for
      View." Subscribers can receive 1.5 category 1 CME credits by completing the CME
      quiz that accompanies this issue of In the Clinic. The content of In the Clinic
      is drawn from the clinical information and education resources of the American
      College of Physicians (ACP), including PIER (Physicians' Information and
      Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program).
      Annals of Internal Medicine editors develop In the Clinic from these primary
      sources in collaboration with the ACP's Medical Education and Publishing division
      and with assistance of science writers and physician writers. Editorial
      consultants from PIER and MKSAP provide expert review of the content. Readers who
      are interested in these primary resources for more detail can consult
      www.acponline.org, http://pier.acponline.org, and other resources referenced
      within each issue of In the Clinic.

PMID- 22473446
TI  - Chromatin Immunoprecipitation (ChIP) using Drosophila tissue.
AB  - Epigenetics remains a rapidly developing field that studies how the chromatin
      state contributes to differential gene expression in distinct cell types at
      different developmental stages. Epigenetic regulation contributes to a broad
      spectrum of biological processes, including cellular differentiation during
      embryonic development and homeostasis in adulthood. A critical strategy in
      epigenetic studies is to examine how various histone modifications and chromatin
      factors regulate gene expression. To address this, Chromatin Immunoprecipitation
      (ChIP) is used widely to obtain a snapshot of the association of particular
      factors with DNA in the cells of interest.    ChIP technique commonly uses
      cultured cells as starting material, which can be obtained in abundance and
      homogeneity to generate reproducible data. However, there are several caveats:
      First, the environment to grow cells in Petri dish is different from that in
      vivo, thus may not reflect the endogenous chromatin state of cells in a living
      organism. Second, not all types of cells can be cultured ex vivo. There are only
      a limited number of cell lines, from which people can obtain enough material for
      ChIP assay.    Here we describe a method to do ChIP experiment using Drosophila
      tissues. The starting material is dissected tissue from a living animal, thus can
      accurately reflect the endogenous chromatin state. The adaptability of this
      method with many different types of tissue will allow researchers to address a
      lot more biologically relevant questions regarding epigenetic regulation in
      vivo(1, 2). Combining this method with high-throughput sequencing (ChIP-seq) will
      further allow researchers to obtain an epigenomic landscape.

PMID- 22473447
TI  - [The contribution of Carlos Chagas Filho to the institutionalization of
      scientific research in Brazilian universities].
AB  - This paper studies the period considered the 'prehistory' of the Instituto de
      Biofisica, namely between November 1937 and October 1945, during which Carlos
      Chagas Filho championed the inclusion of scientific research at Universidade do
      Brasil (UB), despite facing multiple and complex obstacles. The lack of
      successful precedents at UB isolated him to one inexpressive chair. The equipment
      available was inadequate for his purposes; there were no official sources and
      forms of access to funding for science or trained personnel for research
      activities. On the other hand, Chagas Filho won over allies due both to the
      political and social clout of his name and his marriage, and to his scientific
      influence ensuing from his success in attaining the goals he fought for.

PMID- 22473448
TI  - [Carlos Chagas Filho: an articulator of the history of sciences in Brazil].
AB  - A letter sent in 1982 by a group of scientists to the president of Conselho
      Nacional de Desenvolvimento Cientifico e Tecnologico appealed for a policy of
      preservation of Brazilian scientific culture. The name of Carlos Chagas Filho
      topped the list of signatures thereby proving his commitment to that proposal,
      the ideological structure of which was part of his experience in scientific
      policy in Brazil and abroad. This document harks back to the practice of the
      history of the sciences in Brazil and the creation of places for the safeguard
      and organization of scientific memory, such as the Museu de Astronomia e Ciencias
      Afins, Casa de Oswaldo Cruz and the Sociedade Brasileira de Historia da Ciencia,
      of which Carlos Chagas Filho was an inaugural member of the board of directors.

PMID- 22473449
TI  - IBS: New insights into pathogenesis of diarrhea-predominant IBS.

PMID- 22473450
TI  - Endoscopy: NBI in Barrett esophagus--look more and sample less.

PMID- 22473451
TI  - Liver: Activation of NF-kappaB signaling in hepatocytes induces liver fibrosis.

PMID- 22473452
TI  - Therapy: Gastric electrical stimulation relieves nausea and vomiting in the long
      term.

PMID- 22473453
TI  - Non-invasive in vivo detection of peripheral limb ischemia improvement in the rat
      after adipose tissue-derived stromal cell transplantation.
AB  - BACKGROUND: Adipose tissue-derived stromal cells (ADSCs) might help repair
      ischemic cardiovascular tissue. Their in vivo effects on the bioenergetics and
      microcirculation of ischemic muscle through a variety of non-invasive techniques
      was examined. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in 42
      rats. One day after femoral artery ligation, 6 rats per group were randomly
      injected with intramuscularly allogeneic ADSCs (10(6)-10(7)-10(8) cells/ml),
      conditioned media from ADSC cultures (conditioned media [CM], control), saline
      (control), allogeneic fibroblasts (10(7) cells/ml, control) or a non-conditioned
      medium (control). Rats underwent magnetic resonance angiography (MRA), short-time
      inversion recovery (STIR) edema-weighed imaging, proton MR spectroscopy ((1)H
      MRS), thermal infrared imaging (IRI), immunoblotting and immunofluorescence
      analysis on both hindlimbs for 4 weeks. MRA and STIR documented arterial
      occlusion and ischemia, respectively. Muscle (1)H-MRS and IRI showed reductions
      of total creatine (tCr)/water and skin temperature in occluded hind limbs,
      respectively. At 4 weeks, the ADSC and CM groups had greater recovery of skin
      temperature and tCr/water in ischemic limbs compared with controls (P<0.01), with
      increased expression of alpha-sarcomeric actinin and vascular growth factors,
      such as hepatocyte growth factor (HGF), increased vessel density (capillaries,
      arterioles and venules) and less type III collagen. CONCLUSIONS: Allogeneic ADSCs
      improve ischemic muscle metabolism, increase neovasculogenesis and decrease
      fibrosis, largely through a paracrine mechanism. (1)H-MRS and IRI are useful
      tools to monitor attempts at salvaging the ischemic tissues with cell-derived
      novel therapies.

PMID- 22473454
TI  - Clinical significance of flow-mediated dilation, brachial intima-media thickness
      and pulse wave velocity in patients with and without coronary artery disease.
AB  - BACKGROUND: Little is known about the interrelationships among brachial flow
      mediated vasodilatation (bFMD), brachial-ankle pulse wave velocity (baPWV) and
      brachial intima-media thickness (bIMT) in patients with and without coronary
      artery disease (CAD). METHODS AND RESULTS: Two-hundred consecutive patients with
      stable angina pectoris (SAP) were enrolled as the CAD group and 50 age-, sex- and
      body mass index-matched patients without CAD were selected as the non-CAD group.
      bFMD, diastolic blood pressure (DBP) and high-density lipoprotein cholesterol
      (HDL-C) in the CAD group were significantly lower. The CAD group showed
      significantly higher levels of hemoglobin A(1c)(HbA(1c)) and low-density
      lipoprotein cholesterol (LDL-C), but not baPWV. CAD was independently associated
      with bFMD, DBP, HbA(1c) and HDL-C. bFMD and HDL-C significantly decreased and LDL
      C increased as the number of diseased vessels with significant stenosis
      increased. The number of diseased vessels was independently associated with bFMD
      and HDL-C. In addition, bFMD, bIMT, the time constant of the shear rate and the
      time constant of the flow rate as assessed by a new program, Trend Plus((r)),
      were associated with the presence of CAD. Among these parameters, the presence of
      CAD was independently associated with bIMT as well as bFMD. CONCLUSIONS: bFMD was
      a better predictor of the severity of CAD than either baPWV or coronary risk
      factors in patients with SAP. In addition, bIMT may be a critical predictor of
      CAD.

PMID- 22473455
TI  - An increase in right atrial magnetic strength is a novel predictor of recurrence
      of atrial fibrillation after radiofrequency catheter ablation.
AB  - BACKGROUND: Differences in electrical properties between left and right atria (LA
      and RA) after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are
      currently poorly understood. Magnetocardiograms were used to investigate the
      effect of PVI on bi-atrial magnetic field changes and their relationship to
      clinical outcomes. METHODS AND RESULTS: This study included 71 patients
      undergoing PVI for paroxysmal AF. Magnetocardiograms were recorded at baseline
      and 1 day, 8 weeks, and 24 weeks after ablation. Peak magnitude of LA and RA
      segments on P waves was separately compared before and after PVI. During a 16
      month post-ablation period, 53 (75%) patients were free from AF recurrences. LA
      magnetic strength in patients without recurrence persistently decreased for 24
      weeks and was significantly lower at 8 weeks than that in patients with
      recurrence (1.28+/-0.69 vs. 1.74+/-0.71 pico-Tesla, P=0.02). RA magnetic strength
      in patients with recurrence persistently rose for 24 weeks and was significantly
      higher at 8 weeks than that in patients without recurrence (2.17+/-0.82 vs.
      3.00+/-1.12 pico-Tesla, P=0.001). Multivariate analysis showed RA magnetic
      strength at 8 weeks to be the strongest predictor of AF recurrence (odds
      ratio=3.335; 95% confidence interval=1.181-9.416; P=0.02). CONCLUSIONS: PVI
      resulted in distinct changes in magnetic strength in both the LA and the RA. A
      persistent rise in RA magnetic strength might be a robust predictor of AF
      recurrence after ablation.

PMID- 22473456
TI  - Tissue Doppler imaging-derived myocardial acceleration during isovolumetric
      contraction predicts pulmonary capillary wedge pressure in patients with reduced
      ejection fraction.
AB  - BACKGROUND: Tissue Doppler imaging-obtained isovolumetric myocardial acceleration
      (IVA) is load independent, reportedly predicts systolic functions, and correlates
      with exercise capacity in patients with reduced ejection fraction (EF). We
      hypothesized that IVA correlates with the pulmonary capillary wedge pressure
      (PCWP) in patients with reduced EF. METHODS AND RESULTS: Of 113 patients,
      correlations between PCWP and IVA were done for all patients, 48 patients with EF
      >=55%, and 65 patients with EF <55%. Results were compared to the correlation
      between PCWP and other echocardiographic predictors. IVA correlated moderately
      with PCWP in all patients (r=0.54, P<0.0001) and was comparable to the E/A and
      E/e' ratios. In patients with EF >=55%, IVA lost correlation and the only
      predictor was the E/e' ratio (r=0.08, 0.58, P=0.58, <0.0001). In patients with EF
      <55%, IVA was better than E/A and E/e' (r=0.72, 0.61, 0.51, P<0.0001), especially
      for atrial fibrillation or when E/e' fell between 8 and 15. Furthermore, IVA
      >1.60 m/s(2) can predict PCWP >=15 mmHg, with a sensitivity of 95%, specificity
      of 73%, and an area under the curve of 0.867 (P<0.0001). CONCLUSIONS: IVA can
      predict PCWP in patients with reduced EF, and can be considered an alternative to
      the E/e' ratio for patients with atrial fibrillation or E/e' ratio between 8 and
      15.

PMID- 22473457
TI  - Impact of ejection fraction on long-term outcome after elective aortic valve
      replacement in octogenarians with aortic stenosis.
AB  - BACKGROUND: Aortic stenosis (AS) is increasingly common in the elderly
      population. A recent invention of transcatheter aortic valve implantation tends
      to tilt the risk-benefit balance to favor earlier elective intervention for AS.
      Hence, decision making for elective intervention in octogenarians gradually
      becomes important. However, the outcome after elective aortic valve replacement
      (eAVR) has not been evaluated adequately. This study aimed to identify risk
      factors after eAVR in octogenarians and investigate their influence on long-term
      outcome. METHODS AND RESULTS: One hundred and thirty-seven consecutive Japanese
      octogenarians with AS who underwent eAVR were studied. The mean follow-up period
      was 35+/-22 (range, 0-88) months. Long-term overall survival rates after eAVR
      were 92.0%, 85.2% and 75.5% at 1, 3 and 5 years, respectively. Cox proportional
      hazards model identified age [hazard ratio (HR) 1.23; 95% confidence interval
      (CI) 1.07-1.43; P<0.01)] and ejection fraction (EF) <50% (HR 3.38; 95%CI 1.34
      8.52; P<0.01) as the risk factors of mortality. Post-eAVR survival rates in
      octogenarians with an EF >=50% and <50% were 97.3% and 70.4% at 1 year, 90.1% and
      65.3% at 3 years, and 84.3% and 39.2% at 5 years, respectively (P<0.0001).
      CONCLUSIONS: Octogenarians with preserved LV systolic function before surgery
      have favorable long-term survival after eAVR. However, an EF <50% influences the
      mortality in octogenarian patients. Therefore, eAVR should be considered for
      octogenarians with AS before the progression of LV impairment.

PMID- 22473458
TI  - Effects of valsartan, an angiotensin II receptor blocker, on coronary
      atherosclerosis in patients with acute myocardial infarction who receive an
      angiotensin-converting enzyme inhibitor.
AB  - BACKGROUND: The aim of the present study was to assess the effects of angiotensin
      II receptor blocker (ARB) on coronary plaque progression in patients with acute
      myocardial infarction (AMI) who received an angiotensin-converting enzyme
      inhibitor (ACEI). METHODS AND RESULTS: After local ethics committee approval and
      obtaining of informed consent, 116 patients with AMI were randomly assigned to
      receive a combination of valsartan and captopril or captopril alone. Non-culprit
      intermediate coronary atherosclerosis was assessed on intravascular ultrasound.
      The primary and secondary endpoints were the nominal change in percent atheroma
      volume (PAV) and percent change in lumen volume (%DeltaLV), respectively. The
      combination group had a significantly lower systolic blood pressure (117 vs. 125
      mmHg; P=0.02) and a lower plasma aldosterone level (56 vs. 75 pg/ml; P=0.02) at
      follow-up. The nominal change in PAV was slightly lower in the combination group
      than in the ACEI group (-1.9 vs. -0.68%, P=0.06). %DeltaLV was -0.3% in the ACEI
      group and was 4.3% in the combination group (P=0.03). Logistic regression
      analysis showed that additional ARB therapy was independently associated with LV
      enlargement (odds ratio, 2.144; 95% confidence interval: 1.818-5.618; P=0.03).
      CONCLUSIONS: In this study of patients with AMI, additional ARB therapy had
      minimal impact on the progression of coronary atherosclerosis as compared with an
      ACEI alone. The combination of these 2 drugs, however, induces coronary artery
      enlargement.

PMID- 22473459
TI  - Structurally modified 1,10-phenanthroline based fluorophores for specific sensing
      of Ni2+ and Cu2+ ions.
AB  - We report two fluorophores with open coordination sites for specific sensing of
      Ni(2+) and Cu(2+) ions via a simple synthetic route. The fluorescence activity
      was completely quenched on coordination of the metal ions with the phenanthroline
      ring present in the fluorophore as is clearly evident from the photophysical
      studies.

PMID- 22473460
TI  - Controlled generation of singlet oxygen by a water-soluble meso-pyrenylporphyrin
      photosensitizer through interaction with DNA.
AB  - An electron donor-connecting water-soluble porphyrin, meso-(1-pyrenyl)-tris(N
      methyl-p-pyridinio)porphyrin, did not demonstrate singlet oxygen generating
      activity under photo-irradiation. The interaction with DNA successfully recovered
      the photosensitized singlet oxygen generation by this porphyrin.

PMID- 22473461
TI  - Coexistence of a myeloproliferative disorder and secondary polycythemia in the
      same patient.

PMID- 22473462
TI  - High activity mesoporous copper doped cerium oxide catalysts for the total
      oxidation of polyaromatic hydrocarbon pollutants.
AB  - The doping of mesoporous ceria with copper significantly enhances activity for
      naphthalene total oxidation, the enhanced performance is controlled by the
      increased concentration of surface oxygen defects.

PMID- 22473463
TI  - Anatomical plasticity in the adult zebra finch song system.
AB  - In many songbirds, vocal learning-related cellular plasticity was thought to end
      following a developmental critical period. However, mounting evidence in one such
      species, the zebra finch, suggests that forms of plasticity common during song
      learning continue well into adulthood, including a reliance on auditory feedback
      for song maintenance. This reliance wanes with increasing age, in tandem with age
      related increases in fine motor control. We investigated age-related
      morphological changes in the adult zebra finch song system by focusing on two
      cortical projection neuron types that 1) share a common efferent target, 2) are
      known to exhibit morphological and functional change during song learning, and 3)
      exert opposing influences on song acoustic structure. Neurons in HVC and the
      lateral magnocellular nucleus of the anterior nidopallium (LMAN) both project to
      the robust nucleus of the arcopallium (RA). During juvenile song learning and
      adult song maintenance, HVC promotes song syllable stereotypy, whereas LMAN
      promotes learning and acoustic variability. After retrograde labeling of these
      two cell types in adults, there were age-related increases in dendritic arbor in
      HVC-RA but not LMAN-RA neurons, resulting in an increase in the ratio of HVC
      RA:LMAN-RA dendritic arbor. Differential growth of HVC relative to LMAN dendrites
      may relate to increases in song motor refinement, decreases in the reliance of
      song on auditory feedback, or both. Despite this differential growth with age,
      both cell types retain the capacity for experience-dependent growth, as we show
      here. These results may provide insights into mechanisms that promote and
      constrain adult vocal plasticity.

PMID- 22473464
TI  - [Delirium caused by nonconvulsive status epilepticus].
AB  - We report about a patient (66 years) who was referred to our psychiatric hospital
      because of a progressive confusional state with acute onset. The colleagues of
      the referring psychiatric hospital considered a first manic episode as the cause
      of the symptoms and under therapy with haloperidol the confusional state had
      shown a progression.The clinical examination's findings were a mild central
      facial paresis on the right side and a mild hemiparesis on the right side with
      elevated reflex levels.The patient was disoriented, he had cognitive and mnestic
      deficits. His reasoning was slowed, incoherent and perseverating. The patient had
      a slight euphoria.An EEG recording showed a continuous regional EEG-seizure
      pattern. In combination with the clinical symptoms we diagnosed a nonconvulsive
      status epilepticus. Under anticonvulsive treatment with Lorazepam and Valproic
      acid the status epilepticus sustended but a control EEG recording showed signs of
      a Valproate-encephalopathy. Under treatment with Topiramate symptoms ameliorated
      but due to a vascular dementia the patient still showed fluctuating symptoms of
      cognitive and mnestic disturbances.

PMID- 22473465
TI  - [Pathogenetic and salutogenetic aspects of physicians' health].
AB  - OBJECTIVE: To analyse pathogenetic and salutogenetic processes of physicians
      suffering from depression, burnout and drug addiction. METHODS: Qualitative
      follow-up interviews with 32 former physician patients from the Oberbergkliniken
      hospital group. RESULTS: Long working hours, bureaucratic restrictions and double
      burdens of combining family life and professional demands are major pathogenetic
      strains. They interact with biographic performance scripts. Major salutogenetic
      factors are the expansion of self care with regard to physical, spiritual and
      social needs and the reconstruction of resources outside the job. CONCLUSIONS:
      Prevention programmes for health care professionals should focus on the
      reflection of biographic performance scripts, on maintaining multifaceted sources
      of gratification and the buildup of extra-professional resources.

PMID- 22473466
TI  - Head and neck cancer in transplant recipients.
AB  - OBJECTIVES/HYPOTHESIS: The development of malignancy in organ transplant patients
      is a well-known complication of long-term immunosuppressive therapy. We sought to
      characterize our institution's 20-year experience with head and neck cancer after
      solid organ transplantation. STUDY DESIGN: Retrospective review. METHODS:
      Patients who underwent a solid organ transplant with subsequent development of a
      head and neck malignancy, including cutaneous and noncutaneous (upper
      aerodigestive tract and salivary gland) cancers, from January 1990 through
      December 2011 were identified. Patients were stratified according to cancer type,
      location, stage, and survival and compared to a nontransplant cohort in our
      institution's tumor registry. RESULTS: Of 95 patients identified, 17 had
      noncutaneous and 78 had cutaneous head and neck malignancies post-transplant.
      Among the noncutaneous group, no statistically significant differences occurred
      in age, gender, stage, or 5-year survival status when compared to the
      nontransplant tumor registry cohort. However, significantly fewer transplant
      patients were alive at 1 year. Among the cutaneous group, >50% had multiple
      malignancies. The total incidence of head and neck cancer following organ
      transplantation was 2.6%. CONCLUSIONS: Although the development of head and neck
      cancer is a rare side effect of immunosuppression, it still warrants attention.
      These patients have been found to be less likely to survive >1 year when compared
      to their nontransplant counterparts. Patients who develop head and neck
      malignancies following organ transplantation require aggressive screening,
      treatment, and follow-up, as this diagnosis may portend a poor prognosis.

PMID- 22473467
TI  - The Role of Attitudes, Family, Peer and School on Alcohol Use, Rule Breaking and
      Aggressive Behavior in Hispanic Delinquent Adolescents.
AB  - OBJECTIVE: The purpose of this study was to examine ecodevelopmental risk factors
      associated with alcohol uses, rule breaking and aggressive behaviors among
      Hispanic delinquent adolescents. Specifically, this study tests the effect of
      attitudes, family, peer, and school bonding on alcohol use, rule breaking and
      aggressive behaviors in Hispanic delinquent youth.  METHODS: A sample of 235
      heterogeneous Hispanic delinquent adolescents was recruited through referrals
      from the Miami-Dade County's Department of Juvenile Services and from the Miami
      Dade County Public School system. Logistic regression methods were utilized to
      examine the independent effect of each risk factor (attitudes, family, peer,
      school) and to determine the extent to which these factors are associated with
      alcohol use, rule breaking and aggressive behaviors.  RESULTS: Family functioning
      was inversely and significantly related to past 90-day alcohol use in univariate
      regression (beta = -.24, p = .035) but was not significant in multiple regression
      (beta = -0.09, p = .556). Peer alcohol use (beta = 2.02, p<0.001) and poor
      alcohol attitudes (beta =0.59, p=0.006) were positively and significantly related
      to past 90-day alcohol use in the final model. Poor alcohol attitudes, family
      functioning, peer alcohol use, and school bonding were all significantly related
      to both rule breaking and aggressive behaviors in the final model.  CONCLUSIONS:
      Findings highlight the importance of identifying risk factors at multiple levels
      to prevent/reduce alcohol use, rule breaking and aggressive behaviors among
      Hispanic delinquent youth.

PMID- 22473468
TI  - The functions and regulation of the PTEN tumour suppressor.
AB  - The importance of the physiological function of phosphatase and tensin homologue
      (PTEN) is illustrated by its frequent disruption in cancer. By suppressing the
      phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway
      through its lipid phosphatase activity, PTEN governs a plethora of cellular
      processes including survival, proliferation, energy metabolism and cellular
      architecture. Consequently, mechanisms regulating PTEN expression and function,
      including transcriptional regulation, post-transcriptional regulation by non
      coding RNAs, post-translational modifications and protein-protein interactions,
      are all altered in cancer. The repertoire of PTEN functions has recently been
      expanded to include phosphatase-independent activities and crucial functions
      within the nucleus. Our increasing knowledge of PTEN and pathologies in which its
      function is altered will undoubtedly inform the rational design of novel
      therapies.

PMID- 22473469
TI  - New temptations in SMC research.

PMID- 22473471
TI  - A novel animal model of underactive bladder: analysis of lower urinary tract
      function in a rat lumbar canal stenosis model.
AB  - AIMS: An animal model of neurogenic underactive bladder (UAB) has not been
      established. It was reported that a rat lumbar spinal canal stenosis (LCS) model
      created by cauda equina compression manifested intermittent claudication and
      allodynia. In this study, we examined the lower urinary tract function of the rat
      LCS model. METHODS: One small hole was drilled at the fifth lumbar vertebral arch
      (sham), and a rectangular piece of silicone rubber was inserted into the L5-L6
      epidural space (LCS). Before and after surgery, a metabolic cage study was
      performed. After surgery, awake cystometry (CMG) and an in vitro muscle strip
      study were performed. Bladder morphology was evaluated by hematoxylin and eosin
      staining. RESULTS: The LCS rats showed a significant decrease in voided volume
      and a significant increase in postvoid residual volume and residual urine rate
      compared with Sham rats. CMG showed that the postvoid residual urine volume and
      numbers of non-voiding contractions significantly increased, while the voided
      volume, threshold pressure, and maximum intravesical pressure during voiding
      significantly decreased. There were no significant differences between sham and
      LCS rats in response to carbachol. In contrast, there was a significant increase
      in response to field stimulation, especially at lower frequencies, in LCS rats.
      LCS rats showed no obvious difference in detrusor morphology. CONCLUSIONS: This
      rat model requires a relatively simple surgical procedure and has characteristics
      of neurogenic UAB. It seems to be useful in the pathophysiological elucidation of
      UAB and might have potential for assessment of pharmacotherapy of UAB.

PMID- 22473472
TI  - Physical activity and environment perception among older adults: a population
      study in Florianopolis, Brazil.
AB  - OBJECTIVE: To estimate the prevalence of the practice of leisure-time physical
      activity in older adults and to analyze its association with environment
      perception. METHODS: Cross-sectional population study conducted from September
      2009 to June 2010 with 1.656 individuals aged 60 years or older, living in the
      urban zone of the city of Florianopolis, Southern Brazil. Leisure-time physical
      activity was measured using the long version of the International Physical
      Activity Questionnaire. Environment perception variables were measured by means
      of a modified version of the Neighborhood Environment Walkability Scale. Crude
      and adjusted analyzes were carried out using Poisson regression with a 5%
      significance level. RESULTS: The prevalence of leisure-time physical activity was
      29.7% (95% CI: 26.0; 33.3); 35.6% (95%CI: 29.7; 41.6) among men and 26.3% (95%CI:
      23.1; 29.4) among women. The elderly who reported the existence of sidewalks,
      bike lanes, pedestrian paths and trails in the neighborhood, as well as those who
      reported receiving support from friends or neighbors to engage in physical
      activities, were more active in their leisure time. Concerning the influence of
      the climate, the elderly who reported that it was a barrier were rated as more
      active. CONCLUSIONS: The practice of leisure-time physical activity still has low
      prevalence among the elderly population of Florianopolis. Public spaces for the
      practice of physical activity and encouraging group activities may play a
      significant role in the promotion of leisure-time physical activity in older
      adults.

PMID- 22473473
TI  - Factors associated with duration of disability benefits: a cohort study.
AB  - OBJECTIVE: To analyze factors associated with the duration of disability benefits
      due to work-related upper-limb musculoskeletal disorders. METHODS: Ambispective
      cohort study conducted with 563 insured workers from the General Social Security
      System who received temporary disability benefits due to work-related upper-limb
      musculoskeletal disorders in the city of Salvador, Northeastern Brazil, in 2008.
      The data came from an inquiry performed by the Regional Audit of the National
      Social Security Institute and from administrative records. Sociodemographic and
      work-related variables were analyzed, as well as characteristics of the health
      problem and aspects related to social security. Factors associated with time
      until the cessation of the benefit were identified through survival analysis
      techniques. RESULTS: Low socioeconomic position (RR=1.29; 95% CI 1.02; 1.64), age
      below 39 years (RR=1.23; 95% CI 1.03; 1.47), income replacement by the National
      Social Security Institute < 100% (RR=1.24; 95% CI 1.04; 1.47) and high
      expectation of returning to work (RR=1.20; 95% CI 1.00; 1.44) are the categories
      related to higher rate of cessation of the benefit and with its shorter duration.
      CONCLUSIONS: Factors that are not strictly medical, like socioeconomic position,
      age, expectation of returning to work and level of income replacement by the
      National Social Security Institute, seem to influence the benefit's duration.
      These hypotheses need to be tested with further confirmatory studies in order to
      improve the understanding of the process of determining incapacity for work.

PMID- 22473470
TI  - Molecular mechanisms and potential functions of histone demethylases.
AB  - Histone modifications are thought to regulate chromatin structure, transcription
      and other nuclear processes. Histone methylation was originally believed to be an
      irreversible modification that could only be removed by histone eviction or by
      dilution during DNA replication. However, the isolation of two families of
      enzymes that can demethylate histones has changed this notion. The biochemical
      activities of these histone demethylases towards specific Lys residues on
      histones, and in some cases non-histone substrates, have highlighted their
      importance in developmental control, cell-fate decisions and disease. Their
      ability to be regulated through protein-targeting complexes and post
      translational modifications is also beginning to shed light on how they provide
      dynamic control during transcription.

PMID- 22473475
TI  - Directed secondary interactions in transition metal complexes of tripodal pyrrole
      imine and amide ligands.
AB  - Tripodal pyrrole imine and amide ligands provide platforms for combined primary
      and secondary coordination sphere interactions in square planar Pd and Cu, and
      octahedral Ti complexes.

PMID- 22473474
TI  - Facilitated CO2 transport membranes utilizing positively polarized copper
      nanoparticles.
AB  - We suggest copper nanoparticles as a CO(2) carrier by employing the ionic liquid
      BMIM(+)BF(4)(-) for facilitated transport membranes. The copper nanoparticles
      were prepared by dissociating the copper metal into the ionic liquid as a facile
      synthesis. The interactions between BF(4)(-) of the ionic liquid and the surface
      of copper nanoparticles caused the Cu surface to be partially positively charged,
      resulting in increased activity in copper-CO(2) complexation.

PMID- 22473476
TI  - [Supported own initiative of rehabilitation patients ("new credo") - a successful
      model?].
AB  - BACKGROUND: In recent years, rehabilitation aftercare has become an important
      topic in rehabilitation research and practice. This development was initiated by
      the lack of long-term effects after rehabilitation treatment and by the deficits
      identified in several reviews of aftercare recommendations and of actual practice
      of aftercare. Against this background, a new aftercare strategy was developed,
      the "New Credo", which focused aftercare from the beginning of rehabilitation
      treatment. A substantial element of the concept is the resumption and maintenance
      of physical activity in everyday life of the rehabilitation patient. The goal of
      the present study was the evaluation of this concept in a sample of patients with
      chronic back pain. METHOD: The "New Credo" was evaluated in a multi-centre,
      prospective controlled longitudinal study with 3 points of measurement (before
      and after rehab as well as after 12 months). 6 rehabilitation clinics in
      Schleswig-Holstein were included in the intervention arm (IG, 3 clinics) and in
      the control arm (CG, 3 clinics), participants were rehabilitants with chronic
      back pain. The clinics in the intervention arm implemented "the New Credo" in
      accordance with their local conditions. During the study period they were
      provided with a person who was responsible for managing aftercare activities for
      patients. Participants in the CG received standard rehabilitation treatment
      according to general guidelines. Restriction of social participation, disability
      days and restriction in functional capacity in everyday life were defined as
      primary outcomes. Complete data were available for 166 rehabilitants in the IG
      and 368 in the CG. RESULTS: At the end of rehabilitation rehabilitants in the IG
      reported significantly higher use of treatment offerings and more intensive
      preparation for the time after rehabilitation treatment than rehabilitants in the
      CG. Rehabilitants in the IG found recommendations for the time after treatment
      significantly better than those in the CG. As expected, both rehabilitants in the
      IG and in the CG showed similar outcomes directly after inpatient treatment. With
      respect to long-term effects 12 months later, significant differences with
      moderate effect sizes were observed in 2 of the 3 primary outcomes (function
      capacity and social participation) in favour of the IG. With respect to secondary
      outcomes, rehabilitants in the IG showed significantly better long-term results
      than those in the CG. DISCUSSION AND CONCLUSION: Our results show that the "New
      Credo" can successfully be implemented into rehabilitation practice. The "New
      Credo" was positively rated by clinicians and rehabilitants. Rehabilitants in the
      IG found offerings of supported aftercare very helpful. The intensity of actual
      use of aftercare by rehabilitants as well as the emphasis laid on aftercare by
      clinicians indicate that treatment was focused on aftercare over the whole time
      of rehabilitation and that the rehabilitants transferred these aspects into
      everyday life. For the rehabilitants in the IG higher long-term effects could be
      observed compared to those in the CG. This suggests an improved sustainability of
      rehabilitation effects and a successful transfer of acquired knowledge and self
      efficacy in everyday life.

PMID- 22473477
TI  - [Documentation of comorbid mental disorders in medical rehabilitation: an
      analysis of discharge reports].
AB  - OBJECTIVES: Patients with chronic somatic -diseases often suffer from
      psychological distress and mental disorders, which remain unrecognized in somatic
      rehabilitation. The present -study aimed to investigate whether the
      implementation of a stepwise psychodiagnostic procedure improves the
      documentation of psychological distress and mental disorders as well as of the 
      related inpatient treatments and aftercare recommendations. METHODOLOGY:
      Implementation of a stepwise psychodiagnostic procedure in 5 orthopaedic,
      cardiologic and oncologic inpatient rehabilitation clinics. The 4 steps comprised
      (1) screening, (2) in-depth psychodiagnostic assessment, (3) diagnosis and
      treatment, (4) documentation. Implementation efficacy in terms of a better
      documentation was evaluated by comparing the discharge reports of every fifth
      screening-positive and screening-negative patient (n=146) with historical
      discharge reports of the last 3 months preceding baseline assessment (n=161).
      RESULTS: Mental disorders (26,0% vs. 21,7%), general psychological treatment
      (75,3% vs. 66,5%), specific psychological treatment (32,9% vs. 31,7%), as well as
      psychologically relevant aftercare recommendations (41,1% vs. 34,8%) were more
      frequently documented in the current post-implementation discharge reports
      compared to the historical discharge reports. A significant difference was found
      only for the documentation of general psychological treatment. CONCLUSION: The
      results suggest that the implementation of a stepwise psychodiagnostic procedure
      improves the documentation of psychological distress and mental disorders as well
      as related inpatient treatments and aftercare recommendations. Continuous staff
      training and quality assurance relative to the discharge reports may contribute
      to further enhancing the documentation of psychological distress and mental
      disorders.

PMID- 22473478
TI  - [Improvements in patient education from the didactical point of view].
AB  - The findings of empirical educational research and the theoretical and
      experiential knowledge of general didactics and specific didactics of relevant
      subjects are not adequately considered in the conception and implementation of
      patient education. The aim of this work is to screen the results of existing
      research about the quality of instruction, to deduce quality criteria for patient
      education and to discuss their benefits for the existing practice. The research
      on the quality of instruction was systematically investigated for this purpose.
      Subsequently, the 3 empirically validated quality features: "clear structure",
      "participant-oriented social climate" and "cognitive activation with particular
      attention to domain-specific components of teaching" we identified were
      transferred to patient education and concretized by including the theoretical and
      experiential knowledge of didactics. In the process several domains (conception
      of manuals, train-the-trainer seminars) were identified in which the quality
      characteristics can be tied in. The findings of empirical educational research
      are able to complement the existing measures for quality assurance in the area of
      patient education. For this purpose the identification and specification together
      with the possible integration of the 3 quality criteria in the area of patient
      education are a first step.

PMID- 22473479
TI  - [Do we measure the same in all persons? On measurement invariance and response
      shift in rehabilitation research - part 1].
AB  - Subjective constructs like health-related quality of life are often investigated
      in scientific surveys in rehabilitation science, usually assuming that such
      constructs would be equally defined between different groups in case of cross
      sectional control group designs or across time in longitudinal study designs with
      or without control-groups. Differences between measurements of these constructs
      were expected to occur only regarding quantity but not regarding quality.
      However, this assumption cannot be expected to apply in every case and it is
      discussed from a theoretical angle under the terms of invariance or equivalence
      of measurements. Confirmatory factor analysis-based approaches are suitable to
      investigate measurement invariance empirically and will be described in this
      article. These statistical methods are applicable to test whether qualitative
      differences in constructs exist between several groups or time points (response
      shift) and what these differences mean. If measurement invariance cannot be held,
      comparisons of sum scores, which are often used in rehabilitation science, have
      to be considered to be questionable. On the basis of a measurement model specific
      parameters (regression weights, intercepts, measurement errors) can be analyzed
      both between comparison groups and over time. Different kinds of measurement
      invariance exist, depending on the statistical definition of parameters which are
      proven to be equal, and the extent of differences between models. The application
      of confirmatory factor analysis to test measurement invariance in a cross
      sectional design will be described in this article on the example of quality of
      life data from inpatient rehabilitation. Methodological and substantive aspects
      which arise if measurement invariance is disproved will be discussed. In a
      companion article (Jelitte & Schuler, in press) the method will be described for
      a longitudinal study design and results will be discussed in the context of
      response shift research.

PMID- 22473480
TI  - ["Scores of Independence for Neurologic and Geriatric Rehabilitation (SINGER)" -
      development and validation of a new assessment instrument].
AB  - In the context of developing and testing a procedure for "Outcome-oriented
      payment for rehabilitation after stroke", we found that the instruments commonly
      used to measure the outcomes  of rehabilitation after stroke (e. g., Barthel
      Index or FIM) were not meeting the special requirements  of the new payment
      system. Therefore the "Scores of Independence for Neurologic and Geriatric
      Rehabilitation" (SINGER) was developed as a new assessment instrument. This
      instrument is based on the ICF and measures 20 aspects of "independence in
      activities of daily living". The characteristic feature of the SINGER is, above
      all, the way all items are graded in 6 steps: the gradation does not refer to the
      degree of disability but to the kind and amount of help required for the
      respective activity, i. e.: 0 = totally dependent on professional help; 1 =
      professional contact help needed; 2 = contact help by (instructed) lay persons
      sufficient; 3 = preparation or supervision by lay persons still needed; 4 =
      independent with assistive device or still slow; 5 = independent without
      assistive device. For experienced personnel in neurologic rehabilitation, these
      gradations are "intuitively plausible". A manual moreover describes each grade in
      detail for each item so that the instrument can be used in rehabilitation
      facilities without extensive training. The SINGER has been tested and validated
      in a pilot study (n = 100) and in 2 subsequent studies with large case numbers in
      neurologic rehabilitation (n = 1058 and n = 700 patients after stroke in all
      categories of severity). Factor analyses showed that the instrument contains 2
      dimensions which can be interpreted as "physical activities" and "activities of
      communication and cognition". Each of these 2 dimensions can be split into 2 sub
      dimensions that can be assigned to the tasks of therapeutical professions in
      care/Occupational Therapy, physiotherapy, logopedics, and neuro- psychology. The
      test criteria of reliability, sensitivity, convergent validity, floor and ceiling
      effects as well as sensitivity to change show good to very good results.
      Particular emphasis can be given to the high degree of interrater reliability and
      the wide range of possible applications in clinical practice as well as in
      research. A limitation of the instrument to be taken into account is the fact
      that the SINGER has not yet been tested and validated in geriatric rehabilitation
      facilities.

PMID- 22473482
TI  - The stress of misfolding.

PMID- 22473486
TI  - Spurned flies hit the booze.

PMID- 22473487
TI  - Controlling consumption.

PMID- 22473488
TI  - Induction chemotherapy with capecitabine and oxaliplatin followed by
      chemoradiotherapy before total mesorectal excision in patients with locally
      advanced rectal cancer.
AB  - BACKGROUND: Preoperative chemoradiation in patients with locally advanced rectal
      cancer has no impact on overall survival (OS) and distant recurrences. The aim of
      the study was to evaluate local downstaging, toxicity and long-term outcome in
      patients with locally advanced rectal cancer after induction therapy with
      capecitabine and oxaliplatin (CAPEOX) followed by radiotherapy concomitant with
      capecitabine [chemoradiotherapy (CRT)] before total mesorectal excision (TME).
      PATIENTS AND METHODS: Patients with T4 tumors, all T3N+ tumors or T3 tumors
      involving or with a distance <=1 mm to the mesorectal fascia were included.
      Patients were planned for two cycles of CAPEOX followed by radiotherapy
      concomitant with capecitabine. TME was carried out 6 weeks after the completion
      of CRT. RESULTS: Of 84 consecutively admitted patients starting induction CAPEOX,
      77 patients underwent surgery. R0 resection was seen in 94% and T downstaging in
      69%. In the intention-to-treat group, pathological complete response was seen in
      23%. Five-year disease-free survival (DFS) and OS were 63% [95% confidence
      interval (CI), 52.2% to 73.7%] and 67% (95% CI, 56.1% to 77.3%), respectively.
      Grade 3/4 toxicity was seen in 18%, and four deaths occurred within 2 months of
      therapy. CONCLUSION: Induction chemotherapy before CRT and surgery showed a high
      local control rate and promising long-term outcome as OS and DFS.

PMID- 22473489
TI  - Advances in laboratory testing for thrombophilia.
AB  - Testing for hereditary thrombophilia typically includes tests for activated
      protein C resistance (APC-R) and/or factor V Leiden, protein C, protein S,
      antithrombin, and prothrombin G20210A. New options for these assays have become
      available in recent years, with different advantages and disadvantages among the
      currently available methods. Potential interferences for each assay type are
      discussed, including lupus anticoagulants, heparin, warfarin, direct thrombin
      inhibitors (such as argatroban, dabigatran, hirudin, or bivalirudin),
      rivaroxaban, factor deficiencies or elevations, factor V Leiden, and specific
      mutations that the assay(s) might not be able to detect. Causes of acquired
      deficiencies are also described, as these must be carefully excluded before
      diagnosing a hereditary deficiency of protein C, protein S, or antithrombin.

PMID- 22473490
TI  - The relationship between pelvic organ prolapse, genital body image, and sexual
      health.
AB  - AIMS: Pelvic organ prolapse involves physical changes to the genitals,
      potentially distressing to women. We hypothesized poorer genital body image in
      prolapsed women versus controls and that genital body image would correlate with
      sexual health. METHODS: Seventy-four sexually active women, 13 with prolapse, 24
      with surgically corrected prolapse, 37 without prolapse, completed the Genital
      Self Image Scale (GSIS-20), Body Esteem Scale (BES), and Female Sexual Function
      Index (FSFI). RESULTS: In prolapsed women median GSIS-20 scores were 28/40, women
      with surgically corrected prolapse 32/40 and never prolapsed 34/40 (chi(2) = 9.6,
      P < 0.01). Post hoc analysis showed significant differences between prolapsed and
      never prolapsed groups (P < 0.05). After adjusting for BES, GSIS-20 correlated
      with overall FSFI (r = 0.384, P < 0.01), and its subscales of desire (r = 0.34, P
      < 0.05) and satisfaction (r = 0.41, P < 0.01). CONCLUSIONS: Women with prolapse
      are at risk for poorer genital body image and reduced sexual health.

PMID- 22473491
TI  - Oral coadministration of beta-glucuronidase to increase exposure of extensively
      glucuronidated drugs that undergo enterohepatic recirculation.
AB  - Extensive first-pass metabolism can significantly limit a drug's oral exposure
      levels. In this work, we introduce an innovative approach for increasing the oral
      bioavailability of a drug that undergoes extensive reversible glucuronidation and
      enterohepatic recirculation through intraduodenal coadministration of the
      deconjugating enzyme beta-glucuronidase. Intraduodenal administration of JNJ
      10198409 (10 mg/kg) with beta-glucuronidase (34,000-140,000 units/kg) to
      catheterized rats resulted in a significant increase (p < 0.005) in the mean area
      under the plasma concentration versus time curve (AUC; approx. threefold) and
      maximum plasma concentration (C(max); approx. twofold) of JNJ-10198409. The AUC
      and C(max) were 60 +/- 18 ng h/mL and 76 +/- 29 ng/mL, respectively, with no
      enzyme and 177 +/- 55 ng h/mL and 129 +/- 41 ng/mL, respectively, with beta
      glucuronidase coadministered. Moreover, the AUC of the primary glucuronide
      metabolite increased approximately sevenfold from 1173 +/- 361 (ng h)/mL with no
      enzyme coadministered to 8723 +/- 2133 ng h/mL with coadministered enzyme. These
      pharmacokinetic data support the hypothesis that when the primary glucuronide is
      secreted into the duodenum via the bile duct, the glucuronide is converted by
      beta-glucuronidase back to the parent compound. The parent compound is then
      reabsorbed and reconjugated, resulting in elevated systemic exposures to both
      parent and glucuronide. Potential clinical and preclinical applications and
      considerations for this approach are discussed.

PMID- 22473492
TI  - Use of propensity score matching to evaluate a national smoking cessation media
      campaign.
AB  - Sustained mass media campaigns have been recommended to stem the tobacco epidemic
      in the United States. Propensity score matching (PSM) was used to estimate the
      effect of awareness of a national smoking cessation media campaign (EX) on quit
      attempts and cessation-related cognition. Participants were 4,067 smokers and
      recent quitters aged 18-49 in targeted U.S. media markets. Controlling for
      potential confounders through PSM and regression analysis, confirmed awareness of
      EX was not significantly associated with either outcome at 6-month follow-up.
      Matched analyses excluding 217 quitters resulted in a significant effect of EX on
      both outcomes.

PMID- 22473493
TI  - Covariate imbalance and precision in measuring treatment effects.
AB  - Covariate adjustment can increase the precision of estimates by removing
      unexplained variance from the error in randomized experiments, although chance
      covariate imbalance tends to counteract the improvement in precision. The author
      develops an easy measure to examine chance covariate imbalance in randomization
      by standardizing the average covariate difference between the treatment and
      control condition. The standardized covariate difference must not exceed an upper
      bound in order to gain precision in covariate adjusted analysis. The author then
      shows how to select an adequate sample size to mitigate chance covariate
      imbalance and improve precision in small pilot studies.

PMID- 22473494
TI  - Reconciling the multiple objectives of prison diversion programs for drug
      offenders: evidence from Kansas' Senate Bill 123.
AB  - BACKGROUND: In recent years, several states have created mandatory prison
      diversion programs for felony drug possessors. These programs have both
      individual-level goals of reducing recidivism rates and system-level goals of
      reducing prison populations. OBJECTIVE: This study examines the individual level
      and system level impact of Kansas' Senate Bill 123 (SB 123), which created
      mandatory probation/treatment sentences for felony drug possessors. RESEARCH
      DESIGN: A nonrandomized quasi-experimental design was used to evaluate the
      recidivism rates of drug possessors sentenced to SB 123 relative to drug
      possessors sentenced to standard probation, intensive probation, or prison.
      Propensity score matching techniques were used to identify comparison groups.
      Changes in probabilities of prison sentences preimplementation and
      postimplementation were used to assess changes in prison admissions and prison
      populations. SUBJECTS: The treatment group included all eligible drug possessors
      sentenced to SB 123 between November 1, 2003, and October 31, 2006. The
      comparison groups included all eligible drug possessors sentenced to standard
      probation, intensive probation, or prison during the same time period. MEASURES:
      Arrests, violations, revocation resulting in a prison sentence, and reconviction
      resulting in a prison sentence within 24 months of risk in the community served
      as the key individual-level outcome measures. Prison admissions and bed days
      served as the key system-level outcome measures. RESULTS: At the individual
      level, SB 123 increased likelihood of recidivism compared to standard probation
      and had no significant effect compared to intensive probation or prison. At the
      system level, SB 123 diverted offenders from prison at sentencing but only
      marginally reduced prison admissions or saved bed days. CONCLUSIONS: Conflicting
      impacts are a consequence of program design-eligibility requirements diverting
      probation-bound offenders, mandatory sentencing requiring the same diversion
      sentence for all offenders, and diversion sentences longer than those imposed
      preimplementation. Results cast doubt on the effectiveness of mandatory diversion
      programs to achieve both individual-level and system-level impacts.

PMID- 22473496
TI  - Retraction: reducing the harm of stress: medications to rescue the prefrontal
      cortex and overcome bad habits: the science of stress: focus on the brain,
      breaking bad habits, and chronic disease.

PMID- 22473495
TI  - Evaluating free-choice climate education interventions applying propensity score
      matching.
AB  - BACKGROUND AND OBJECTIVES: The majority of environmental education takes place in
      informal settings, of which so-called free-choice learning is typical. What is
      understood by this is a kind of learning which is self-determined and driven by
      the needs and interests of the learner. The voluntariness of participation in
      interventions and the fact that they take place in turbulent action settings lead
      to formidable challenges for impact evaluation, particularly because often no
      randomized control trials (RCTs) or before-and-after measurements can be carried
      out. In this article, the evaluation of five different interventions from a large
      scale program on consumer climate education provides the empirical background for
      illustrating the problems confronting quasi-experimental impact analyses in a
      free-choice context and presenting a possible solution based on propensity score
      matching (PSM). METHOD: In a quasi-experimental control-group design,
      intervention participants and nonparticipants filled out questionnaires featuring
      the same behavioral intentions. The challenges due to selection processes were
      met with radius matching on the basis of sociodemographic characteristics as
      covariates. Sensitivity analyses on the basis of Rosenbaum Bounds and the Hodges
      Lehmann point estimator were used for assessing the robustness of treatment
      effects against unobserved confounding variables. RESULTS: The analyses show that
      all the interventions under study positively influenced intentions to seek
      further advice or information on the topics covered. Furthermore, for all the
      interventions, significant positive effects on the intentions relating directly
      to climate-friendly behavior could be identified. In this context, PSM and
      sensitivity analyses proved to be effective methods. However, there were several
      limitations due to conceptual and methodological issues, and these are discussed
      below.

PMID- 22473499
TI  - Connecting to the future--the promise of telecare.

PMID- 22473497
TI  - Fenofibrate down-regulates renal OCT2-mediated organic cation transport via
      PPARalpha-independent pathways.
AB  - Fibrate drugs, the peroxisome proliferator-activated receptor alpha (PPARalpha)
      agonists, are widely prescribed for the treatment of hyperlipidemia. The present
      study examined the effect of fibrate drugs on renal OCT2 activity in a
      heterologous cell system [Chinese hamster ovary (CHO-K1) cells stably transfected
      with rabbit (rb) OCT2], LLC-PK1, and intact mouse renal cortical slices. We found
      that both in the CHO-K1 cells expressing rbOCT2 and in LLC-PK1 cells, fenofibrate
      significantly inhibited [3H]-MPP+ uptake whereas clofibrate and WY14643 had no
      effect. Surprisingly, the inhibitory effect of fenofibrate was not attenuated by
      GW6471, a PPARalpha antagonist, indicating that the inhibitory process observed
      was via a PPARalpha-independent pathway. Fenofibrate decreased [3H]-MPP+ uptakes
      through a reduction of the maximal transport (J(max)) but without effect on the
      transporter affinity (K(t)) corresponding to a decrease in membrane expression of
      OCT2. Since the inhibitory effect of fenofibrate was not prevented by
      pretreatment with cycloheximide, its inhibitory action did not involve an
      inhibition of protein synthesis. Similar to the effect seen in the cell-cultured
      system, the inhibitory effect of fenofibrate was also observed in intact renal
      cortical slices. Taken together, our data showed that fenofibrate decreased the
      activity of OCT2 by reducing the number of functional transporters on the
      membrane, which is likely to be a PPARalpha-independent pathway.

PMID- 22473500
TI  - Do not treat from CIS onset: evaluate disease course and prognosis first--yes.
AB  - As physicians how do we counsel our patients with clinically isolated syndrome
      (CIS) when they ask, 'what is the benefit of injecting disease-modifying agents
      (DMAs) over many years? What disability will they prevent in my future?' In this
      debate, we will provide three core points supporting the concept that a watchful
      waiting approach (annual neurological evaluation and magnetic resonance imaging
      of the head (with gadolinium) at least for the first few years after diagnosis)
      for most patients with CIS represents appropriate medical care.

PMID- 22473501
TI  - Do not treat from CIS onset: evaluate disease course and prognosis first--no
      (treat!).

PMID- 22473502
TI  - Do not treat from CIS onset: evaluate disease course and prognosis first-
      commentary.

PMID- 22473504
TI  - Intramolecular hydrogen bonding as a synthetic tool to induce chemical
      selectivity in acid catalyzed porphyrin synthesis.
AB  - A straightforward procedure based on the formation of intramolecular hydrogen
      bonds to impart selectivity in the preparation of multi-functionalized porphyrins
      has been developed. To illustrate the concept, the synthesis of a biomimetic
      artificial photosynthetic model able to undergo electron and proton transfer
      reactions upon irradiation is reported.

PMID- 22473505
TI  - [Sometimes the worm is inside: simultaneous double appendicitis].

PMID- 22473506
TI  - [Verification of acute myocardial damage caused by cocaine abuse using MRI].

PMID- 22473507
TI  - [CT-guided marking of pulmonary nodules with a special lung marking wire before
      video-assisted thoracoscopic surgery - review of 184 cases].
AB  - PURPOSE: Minimally invasive techniques like video-assisted thoracoscopic surgery
      (VATS) are currently the method of choice for the resection of small pulmonary
      nodules, when they are located in the periphery of the lungs. To guarantee quick
      and safe intraoperative identification of the nodule, preoperative marking is
      necessary and sensible. We report about our experiences in 184 markings with a
      special lung marking wire, which is placed in or around the pulmonary nodule
      using CT guidance. MATERIALS AND METHODS: In 184 patients (97 m, 87f, mean age:
      58.1 +/- 13.7 years) with pulmonary nodules, scheduled for resection with VATS, a
      special lung marking wire was placed preoperatively under CT guidance. We
      evaluated the technical success, safety, necessity of conversion to thoracotomy
      and histology in all patients. RESULTS: The marking wire could be positioned
      successfully in 181 cases (98.4 %). There was one major complication
      (uncontrollable pneumothorax). Minor adverse events like small pneumothorax (53.3
      %) or a perifocal bleeding (30.4 %) did not necessitate treatment. Complete
      resection of the marked nodule was successful in 98.4 % of the patients.
      Conversion to thoracotomy was necessary in 29 patients (15.9 %) due to bleeding,
      adhesions, malignancy or wire dislocation. Histology revealed a benign nodule in
      96 cases (54.4 %) and a malignant lesion in 78 cases (45.6 %), of which only 21
      nodules (11.5 %) turned out to present a primary pulmonary carcinoma. CONCLUSION:
      CT-guided marking of pulmonary nodules using a special marking wire followed by
      thoracoscopic resection is an efficient and safe method for diagnosing suspicious
      nodules in the periphery of the lung.

PMID- 22473508
TI  - Comparison of a standard and a high-concentration contrast medium protocol for
      MDCT angiography of the lower limb arteries.
AB  - PURPOSE: To prospectively compare a compact bolus (CB) injection protocol using
      high-iodine concentration contrast medium with a standard bolus (SB) injection
      protocol at equi-iodine doses for run-off computed tomographic angiography (CTA).
      MATERIALS AND METHODS: 64 patients with suspected peripheral arterial disease who
      underwent 40 or 64-slice run-off CTA were included in this IRB-approved study.
      Patients were randomized to undergo the CB protocol (32 patients, iomeprol
      400mgI/mL, 100 mL, 4 mL/sec) or the SB protocol (32 patients, iomeprol 300mgI/mL,
      134 mL, 4 mL/sec). Luminal contrast density (CD) values were measured and
      arterial opacification (AO) was scored (5-point scale). Cases of venous overlay
      or bolus overriding were documented. RESULTS: Overall arterial CD was
      significantly higher with the compact bolus (CB: 279 +/- 57HU, SB: 234 +/- 32HU,
      p = 0.0017). Segmental CD was significantly higher (p< 0.05) in 7 of 16 evaluated
      segments. Patency-based comparison revealed superior AO in vessels with relevant
      (50 - 99 %) stenoses (CB: 4.54 vs. SB: 4.18, p = 0.04). Contrast bolus overriding
      without pathological reasons, i. e., acute occlusions, was noted in one patient
      in each group. Venous overlay was observed less frequently in the CB group (CB
      vs. SB: 12 vs. 19 patients, n. s.; 29 of 64 legs [45 %] vs. 44 of 64 legs [69 %],
      p = 0.01). CONCLUSION: At equi-iodine doses, the CB protocol led to a
      quantitatively and qualitatively higher arterial opacification compared to the SB
      protocol. Therefore, a CB protocol should be favored for run-off CTA.

PMID- 22473509
TI  - [Health economics evaluation of magnetic resonance imaging for the staging of
      prostate cancer for Austria and Germany].
AB  - PURPOSE: The aim of this study was the health economics analysis of MR imaging in
      the preoperative staging of patients with prostate carcinoma (PCa). MATERIALS AND
      METHODS: The health economics analysis consisted of the following steps:
      modeling, determination of probabilities and parameters based on a detailed
      literature search, evaluation using the averages of the parameters, and
      sensitivity analyses of the results over the ranges of values. We performed a
      cost-utility analysis from health insurance's perspective for Austria and
      Germany. The population under investigation included patients with confirmed PCa.
      The alternative was a decision for therapy with or without staging using MR
      imaging. A localized PCa was treated by prostatectomy and locally advanced PCa by
      radiation/hormone therapy. The result parameters were quality adjusted life years
      (QALYs) and costs per patient. RESULTS: The evaluation showed that MR imaging is
      useful regarding costs and utilities prior to radical prostatectomy which is
      expensive and may be associated with serious clinical consequences. The costs per
      patient were lower by ? 2635 and the utilities were higher by 0.099 QALYs. The
      strategy without MR imaging for staging was dominated by the strategy using MR
      imaging for staging in the evaluation using the base values and in almost all
      sensitivity analyses. CONCLUSION: For the parameters used and almost all
      scenarios of the sensitivity analysis, our decision-analytic model revealed a
      higher cost-utility ratio for the strategy using MR imaging for the staging of
      PCa.

PMID- 22473511
TI  - Mortality and serum sodium in  CKD--yet another U-shaped curve.
AB  - A consistent association between hyponatremia and increased mortality has been
      shown in hospitalized patients. A new study investigating dysnatremia in non
      dialysis-dependent patients with chronic kidney disease found that both
      hyponatremia and hypernatremia are associated with increased mortality,
      independently of other diseases known to cause hyponatremia.

PMID- 22473510
TI  - Does iron overload really matter in stem cell transplantation?
AB  - A growing body of evidence suggests that iron overload is associated with
      inferior outcomes after myeloablative allogeneic hematopoietic stem cell
      transplantation (HSCT). However, all of those studies used surrogate markers of
      iron overload, especially serum ferritin, and most had a retrospective design. We
      conducted a prospective observational study in patients with myelodysplastic
      syndrome or acute leukemia undergoing myeloablative HSCT. Forty-five patients who
      were followed for over 1 year, with serial measurements of serum iron parameters,
      as well as liver and cardiac magnetic resonance imaging. There was no significant
      increase in ferritin, liver or cardiac iron content in the 12 months following
      HSCT. Although serum ferritin still appeared to have prognostic significance, as
      previously reported, pre-HSCT iron overload (as reflected in liver iron content)
      was not associated with increased mortality, relapse, or graft-versus-host
      disease. These results raise the possibility that the adverse prognostic impact
      of pre-HSCT hyperferritinemia may be related to factors independent of iron
      overload.

PMID- 22473512
TI  - RAS blockade, hyperkalemia  and AKI--look and you will find.
AB  - Aliskiren combined with other inhibitors of the renin-angiotensin system
      increases the risk of hyperkalemia. This risk does not translate into an
      increased incidence of acute kidney injury, suggest the results of a meta
      analysis. However, further research is needed to fully evaluate the safety of
      combination therapy with aliskiren.

PMID- 22473513
TI  - Photosensitizer and vancomycin-conjugated novel multifunctional magnetic
      particles as photoinactivation agents for selective killing of pathogenic
      bacteria.
AB  - Novel multifunctional magnetic particles (MMPs) conjugated with photosensitizer
      and vancomycin were fabricated by surface modification of Fe(3)O(4) particles.
      The capacities to target, capture and inactivate pathogenic bacteria and good
      biocompatibility suggest that the MMPs have great potentials as photodynamic
      inactivation agents for serious bacterial contamination.

PMID- 22473514
TI  - Tibial nerve decompression: reliable exposure using shorter incisions.
AB  - BACKGROUND: Patients and surgeons recognize the value of procedures that minimize
      scarring and tissue dissection, but technical standards do not exist with regards
      to incision lengths needed for tibial nerve decompression. This article
      introduces reproducible techniques that reliably provide exposure for release of
      known anatomical compression points of the tibial nerve, while minimizing the
      length of required skin incisions. METHODS: The senior author's approach to
      decompression of the tibial nerve at the soleus arch and the tarsal tunnel is
      presented. Typical incision lengths and surgical exposure are demonstrated
      photographically. The safety of using this technique is examined by review of the
      medical records of all patients undergoing this procedure from 2003 to 2011,
      looking for technical complications such as unintentional damage to nerves or
      adjacent structures. RESULTS: 224 consecutive patients undergoing 252 total
      procedures underwent release of known anatomical compression points of the tibial
      nerve at either the tarsal tunnel, inner ankle, or the soleus arch. Typical
      incision lengths used for these procedures were 5 cm for the proximal calf and
      4.5 cm for the tarsal tunnel. Review of medical records revealed no incidences of
      unintentional injury to nerves or adjacent important structures. Functional and
      neurological outcomes were not assessed. CONCLUSIONS: Tibial nerve decompression
      by release of known anatomical compression points can be accomplished safely and
      effectively via minimized skin incisions using the presented techniques. With
      appropriate knowledge of anatomy, this can be performed without additional risk
      of injury to the patient, making classically-described longer incisions
      unnecessarily morbid.

PMID- 22473515
TI  - Water avoidance stress results in an altered voiding phenotype in male mice.
AB  - AIMS: We set out to characterize the voiding phenotypes of male mice to a water
      avoidance stress (WAS) protocol and compare the molecular changes with those
      induced by surgically induced partial bladder outlet obstruction (pBOO). METHODS:
      Six-week-old male Swiss Webster mice housed with sibling littermates were
      individually placed on a platform centered in the middle of a water filled basin
      for 1 hr daily for 4 weeks. A non stressed cohort of sibling littermates served
      as controls. Measured end points included voiding frequency, voided volume,
      bladder mass, and in vivo cystometry. Molecular end points included myosin heavy
      chain (MHC) isoform distribution by PCR, and nuclear translocation of hypoxia
      inducible factor (HIF1alpha) and the nuclear factor of activated T-cells (NFAT)
      by gel shift assay. These molecular endpoints were compared with samples from
      male mice undergoing anatomic pBOO. RESULTS: WAS resulted in increased average
      voided volumes and bladder mass, and a decrease in voiding frequency (P < 0.05).
      The slower MHC A isoform was only expressed in the pBOO group that developed
      severe hypertrophy. Gel shift assays revealed substantial increases in HIF1-alpha
      nuclear translocation in the group subjected to pBOO that developed severe
      hypertrophy but minimal changes in the pBOO group that developed minimal
      hypertrophy and the swim stress groups. CONCLUSIONS: The WAS model induces
      moderate bladder wall hypertrophy in the absence of any surgical manipulation.

PMID- 22473516
TI  - Glycosylated diazeniumdiolate-based oleanolic acid derivatives: synthesis, in
      vitro and in vivo biological evaluation as anti-human hepatocellular carcinoma
      agents.
AB  - A series of O(2)-glycosylated diazeniumdiolate-based derivatives of oleanolic
      acid (4-19) were synthesized and their anti-human hepatocellular carcinoma (HCC)
      activities were evaluated. Compound 6 selectively inhibited HCC, but not non
      tumor liver cell proliferation. This inhibition was attributed to high levels of
      nitric oxide (NO) released in HCC cells. Importantly, 6 exhibited low acute
      toxicity (LD(50) = 173.3 mg kg(-1)) and potent inhibition of HCC tumor growth in
      mice (3 mg kg(-1) iv). Furthermore, 6 induced HCC cell apoptosis, which was
      accompanied by lower mitochondrial membrane potentials and Bcl2 expression, but
      with higher cytochrome C release, Bax, caspase 3 and 9 expression activities in
      HCC cells. Collectively, 6 may be a promising candidate drug for the intervention
      of HCC.

PMID- 22473518
TI  - Nickel(II) and copper(II) complexes of beta-unsubstituted 5,15-diazaporphyrins
      and pyridazine-fused diazacorrinoids: metal-template syntheses and peripheral
      functionalizations.
AB  - The present paper reports the first comprehensive study on the synthesis,
      structures, optical and electrochemical properties, and peripheral
      functionalizations of nickel(II) and copper(II) complexes of beta-unsubstituted
      5,15-diazaporphyrins (M-DAP; M = Ni, Cu) and pyridazine-fused diazacorrinoids (Ni
      DACX; X = N, O). These two classes of compounds were constructed starting from
      mesityldipyrromethane by a metal-template method. Ni-DAP and Cu-DAP were prepared
      in high yields by the reaction of the respective metal-bis(dibromodipyrrin)
      complexes with NaN(3)-CuX (X = I, Br), whereas Ni-DACN and Ni-DACO were formed as
      predominant products by the reaction with NaN(3). In both cases, the metal
      centers change their geometry from tetrahedral to square planar during the aza
      annulation; X-ray crystallographic analyses of M-DAPs showed highly planar
      diazaporphyrin pi planes. The Q band of Ni-DAP was redshifted and intensified
      compared with that of a nickel-porphyrin reference, due to the involvement of
      electronegative nitrogen atoms at the meso positions. It was found that the
      peripheral bromination of Ni-DAP and Ni-DACO occurred regioselectively to afford
      Ni-DAP-Br(4) and Ni-DACO-Br, respectively. These brominated derivatives underwent
      Stille reactions with tributyl(phenyl)stannane to give the corresponding
      phenylated derivatives, Ni-DAP-Ph(4) and Ni-DACO-Ph. On the basis of the
      absorption spectra and X-ray analysis, it has been concluded that the attached
      phenyl groups efficiently conjugate with the diazaporphyrin pi system. The
      present results unambiguously corroborate that the beta-unsubstituted DAPs and
      DACXs are promising platforms for the development of a new class of pi-conjugated
      azaporphyrin-based materials.

PMID- 22473517
TI  - MRI study of subconjunctival and intravitreal injections.
AB  - Previous magnetic resonance imaging (MRI) studies to investigate the routes of
      penetration and barriers in ocular delivery have provided insights into the
      mechanisms of transscleral and intraocular drug delivery. The objective of the
      present study was to investigate ocular penetration and clearance after
      subconjunctival and intravitreal injections using a contrast agent at
      concentrations higher than those in the previous studies. This high concentration
      approach was hypothesized to allow the visualization of the contrast agent in the
      eye that could not be achieved previously. Subconjunctival and intravitreal
      injections of contrast agent Magnevist, a model hydrophililc probe, were
      performed in rabbits, and the distribution and clearance of the probe after the
      injections were examined by MRI. After subconjunctival injection in vivo,
      significant contrast agent penetration into the anterior chamber was observed but
      not into the vitreous. A clearance pathway of the hydrophilic probe from the
      subconjunctival depot to the regions near the periocular fat behind the eye was
      found. After intravitreal injection in vivo, the contrast agent was observed in
      the anterior chamber, optic nerve, and tissues surrounding the eye during
      clearance. MRI continues to provide insights into the transport barriers and
      clearance pathways of hydrophilic molecules in ocular delivery.

PMID- 22473520
TI  - Receiver operating characteristic analysis of sphincter electromyography for
      parkinsonian syndrome.
AB  - AIMS: We performed receiver operating characteristic (ROC) analysis to determine
      the ability of sphincter electromyography (EMG) to distinguish multiple system
      atrophy (MSA) from other parkinsonisms. The following was determined: (1) the
      appropriate motor unit potential (MUP) parameter among duration, phase, and
      amplitude; (2) the desirable parameter of our duration criteria; that is, more
      than 20% MUPs having >10 ms duration (criteria a) or mean duration >10 ms
      (criteria b). METHODS: We retrospectively reviewed 441 case records where
      sphincter EMG were performed in patients with parkinsonian syndromes: MSA, n =
      263; Parkinson's disease, n = 129; dementia with Lewy bodies, n = 25; and
      progressive supranuclear palsy, n = 24. We performed ROC analysis of the data
      sets. RESULTS: The area under the curve used to differentiate MSA from other
      parkinsonian syndromes was 0.68 in duration, 0.57 in phase, and 0.51 in
      amplitude, respectively; these values were statistically significant. With regard
      to our duration criteria, area under the curve was 0.69 for the average duration
      of MUPs (criteria b) and 0.67 for percentage of MUPs of duration >10 ms (criteria
      a); these values were also statistically significant. CONCLUSIONS: This study
      suggests that duration is appropriate parameter for the differentiation of MSA.
      However, the area under the curve of the mean duration was insufficient to
      confirm the diagnosis; sphincter EMG should be used as a supportive diagnostic
      tool for the diagnosis of MSA.

PMID- 22473521
TI  - High cut-off hemodialysis and bortezomib-based therapy to rescue kidneys in
      myeloma-dependent cast nephropathy.
AB  - Myeloma-dependent cast nephropathy (MCN) is a medical emergency where prompt
      medical intervention is essential to rescue the kidneys from irreversible damage
      and the patient from lifelong dialysis. Evidence of the benefit of plasma
      exchange in removing serum free light chains (sFLC) has been controversial [1,2].
      According to our recent experience, high cut-off hemodialysis (HCOD) with
      specially designed dialyzers reduces the level of sFLC concentration within hours
      and improves renal function in MCN in the long term when combined with effective
      bortezomib-based chemotherapy.

PMID- 22473523
TI  - Role of hyaluronan synthase 2 to promote CD44-dependent oral cavity squamous cell
      carcinoma progression.
AB  - BACKGROUND: CD44 is a transmembrane receptor found on many different benign and
      malignant cells. Hyaluronan (HA), a major component of the extracellular matrix,
      is the primary ligand for CD44 receptors. In cancer cells, HA interaction with
      CD44 promotes multiple signaling pathways that influence tumor cell progression
      behaviors in a variety of solid tumors. Increasing evidence indicates that HA and
      CD44 signaling play an important role in oral cavity squamous cell carcinoma
      progression. HA is primarily synthesized by hyaluronan synthases, and the current
      study investigated the role of hyaluronan synthase 2 (HAS 2) in oral cavity
      carcinoma progression behaviors. METHODS: Analysis of HAS 2 mRNA and protein
      expression, HA production, and HAS 2-mediated tumor cell proliferation and
      migration behaviors with and without HAS 2 suppression were carried out on 2
      established oral cavity cancer cell lines. Immunohistochemical analysis of HAS 2
      and CD44 expression in oral cavity carcinoma tumor specimens was performed.
      RESULTS: HAS 2 was expressed in the 2 oral cancer cell lines, HSC-3 and SCC-4.
      Suppression of HAS 2 expression resulted in CD44-dependent decreased tumor cell
      migration, decreased tumor cell growth, and increased cisplatin sensitivity,
      suggesting the importance of tumor cell HA production to promote in vitro tumor
      progression behaviors in oral cancer cells. Increased HAS 2 expression in oral
      cavity carcinoma clinical specimens was associated with poor clinicopathologic
      characteristics and worse disease-free survival. CONCLUSIONS: HAS 2 may be a
      potential therapeutic target for the treatment of oral cavity cancer.

PMID- 22473524
TI  - Synthesis and anticonvulsant activity of some 2/3-benzoylaminopropionanilide
      derivatives.
AB  - In this study, the synthesis and anticonvulsant properties of sixteen 2/3
      benzoylaminopropionanilide derivatives were described. Molecular design of the
      compounds has been based on the modification of lacosamide which is a
      functionalized amino acid with a novel anticonvulsant activity. The structural
      confirmation of the title compounds was achieved by spectral and analytical data.
      The anticonvulsant activity profile of synthesized compounds was determined by
      maximal electroshock (MES) and subcutaneous metrazole (scMet) seizure tests,
      whereas their neurotoxicity was examined using rotarod test. All these tests were
      performed in accordance with the procedures of the Antiepileptic Drug Development
      (ADD) program. The majority of the compounds were effective in the MES or scMet
      screening tests. None of the compounds showed neurotoxicity according to the
      rotarod test at studied doses. Most active compounds in the series were 3, 12 and
      13, which bearing 2-methyl, 2-ethyl and 2-isopropyl substituent on the N-phenyl
      ring, respectively.

PMID- 22473525
TI  - Determination of norcantharidin in mouse tissues by liquid chromatography coupled
      to tandem mass spectrometry and its tissue distribution study.
AB  - The purpose of this study is to determine the concentrations of norcantharidin
      (CAS NO: 5442-12-6) in mouse tissues and investigate its tissue distribution
      after intragastric administration of disodium norcantharidate solution. A highly
      sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS/MS)
      method was developed and validated, using ribavirin (CAS NO: 36791-04-5) as the
      internal standard (IS). Norcantharidin and IS were extracted from 0.3 mL tissue
      homogenates using protein precipitation with acetone under acid condition. The
      analyte was separated on a C18 reverse phase column and analyzed by MS/MS in the
      multiple reaction monitoring (MRM) mode using ESI with positive ionization, m/z
      169->123 for norcantharidin and m/z 267->135 for IS. The developed method was
      validated over a linear range of concentrations 0.01~5 MUg.mL - 1 in liver, lung,
      kidney, stomach, small intestine, uterus and testis, 0.005~0.5 MUg.mL - 1 in
      heart, spleen and brain, the correlation coefficients (r2) were between 0.9918
      and 0.9976. The tissue distribution study result was as follows: The AUC0-t of
      norcantharidin in tissues was in the order as follows: small intestine, stomach,
      uterus, kidney, testis, liver, lung, spleen, heart, brain.

PMID- 22473526
TI  - Indoor fine particle (PM2.5) pollution exposure due to secondhand smoke in
      selected public places of Sri Lanka.
AB  - BACKGROUND: Secondhand smoke accounts for a considerable proportion of deaths due
      to tobacco smoke. Although the existing laws ban indoor smoking in public places
      in Sri Lanka, the level of compliance is unknown. METHODS: Fine particulate
      matter (PM(2.5)) levels in 20 public places in Colombo, Sri Lanka were measured
      by a PM monitor (Model AM510-SIDEPAK Personal Aerosol Monitor). Different types
      of businesses (restaurants, bars, cafes, and entertainment venues) were selected
      by purposive sampling. Only the places where smoking was permitted were
      considered. RESULTS: The average indoor PM(2.5) ranged from 33 to 299 ug/m(3).
      The average outdoor PM(2.5) ranged from 18 to 83 ug/m(3). The indoor to outdoor
      PM(2.5) ratio ranged from 1.05 to 14.93. In all venues, indoor PM(2.5) levels
      were higher than the Sri Lankan ambient PM(2.5) standard of 50 ug/m(3). All
      indoor locations had higher PM(2.5) levels as compared to their immediate outdoor
      surroundings. CONCLUSION: The study highlights the importance of improving
      ventilation and enforcing laws to stop smoking in public places.

PMID- 22473527
TI  - The (Zn(0.95)Mn(0.05)S)2.L (L = hexylamine and octylamine) inorganic/organic
      hybrid luminescence films by a spin-coating method.
AB  - The (Zn(0.95)Mn(0.05)S)(2).L (L = hexylamine and octylamine) hybrids show the
      optimal Mn(2+) luminescence and their thin films were fabricated on the quartz
      substrate layer by layer by a spin coating method, which revealed the linear
      relationship of the UV optical absorption and the Mn(2+) luminescence intensity
      with the layer numbers.

PMID- 22473528
TI  - Contribution of the physicochemical properties of active pharmaceutical
      ingredients to tablet properties identified by ensemble artificial neural
      networks and Kohonen's self-organizing maps.
AB  - The aim of this study was to create a tablet database for use in designing tablet
      formulations. We focused on the contribution of active pharmaceutical ingredients
      (APIs) to tablet properties such as hardness and disintegration time (DT). Before
      we investigated the effects of the APIs, we optimized the tablet base formulation
      (placebo tablet) according to an expanded simplex search. The optimal placebo
      tablet showed sufficient hardness and rapid disintegration. We then tested 14
      kinds of compounds as the model APIs. The APIs were characterized in terms of
      their physicochemical properties using Kohonen's self-organizing maps. We also
      prepared model tablets by incorporating the APIs into the optimal placebo tablet,
      and then examined the tablet properties, including tensile strength and DT. On
      the basis of the experimental data, an ensemble artificial neural network
      incorporating general regression analysis was conducted. A reliable model of the
      correlation between the physicochemical properties of the APIs and the tablet
      properties was thus constructed. From the correlation model, we clarified the
      detailed contributions of each physicochemical property to the tablet attributes.

PMID- 22473529
TI  - Nuclear medicine residency vs nuclear radiology fellowship.

PMID- 22473530
TI  - Recalled board questions: perspective of the ABNM.

PMID- 22473531
TI  - ACGME Milestone Project.

PMID- 22473532
TI  - International focus on theragnostics.

PMID- 22473533
TI  - SNM travels to Miami Beach for 2012 annual meeting.

PMID- 22473534
TI  - Vertical rectus abdominis musculocutaneous flow-through flap to a free fibula
      flap for total sacrectomy reconstruction.
AB  - PURPOSE: The purpose of this report of a small series was to describe the
      technique of total sacrectomy reconstruction using a pedicled vertical rectus
      abdominis musculocutaneous (VRAM) flow-through flap anastomosed to a free fibula
      flap. METHODS: We reviewed all consecutive total sacrectomy reconstructions
      performed from 2009 to 2011. Surgical technique and patient outcomes were
      assessed. RESULTS: Total sacrectomy reconstructions included three two-stage and
      three-stage VRAM flow-through flap to free fibula flap patients all of which
      ambulated by discharge. Flap survival was 100%. Pelvic ring defects were
      reconstructed with A-frame fibula flap struts anastomosed to the distal
      epigastric vessels of pedicled trans-pelvic VRAM flaps. Complications such as
      wound healing, infection or hardware failure were not observed. Bony union
      occurred at an average 2.7 +/- 0.6 months. CONCLUSIONS: Total sacrectomy
      reconstruction using a VRAM flow-through flap anastomosed to a two-strut free
      fibular flap allows initial assessment of the recipient vessels during the first
      and ensuing operative stages, satisfies the bone and soft tissue requirements of
      the defect, and provides a durable, functionally optimized reconstruction.

PMID- 22473535
TI  - Synthesis of [18F]BODIPY: bifunctional reporter for hybrid optical/positron
      emission tomography imaging.

PMID- 22473537
TI  - Three-tiered Au nano-disk array for broadband interaction with light.
AB  - We demonstrate a straightforward method to enlarge the spectral window for
      broadband interaction with light, by creating a plasmonic nanostructure composed
      of closely spaced multiple Au nano-disks. The vertically stacked, Au nano-disks
      of three different sizes make it possible to merge the individual spectral
      windows of the internal nano-disks into one broadband window, and can be simply
      generated by a single-step electron-beam lithography step with subsequent sputter
      deposition.

PMID- 22473539
TI  - SUDEP: Sudden Unexpected Death in Epilepsy on Placebo?

PMID- 22473538
TI  - Psychiatric care in epilepsy surgery: who needs it?
AB  - At present there is considerable variability in the psychiatric evaluation and
      follow-up of patients in epilepsy surgery programs globally. There is a large
      body of research now demonstrating heightened risk for psychological disturbance
      in surgically remedial patients before and after surgery. This evidence provides
      a compelling case for the routine provision of psychiatric and psychological
      treatment to optimize the benefits of epilepsy surgery and patient outcomes. In a
      comprehensive model of care, presurgical psychiatric and psychosocial evaluation
      plays an integral role in shaping the team's understanding of surgical candidacy
      and the patient's capacity for informed consent. After surgery, efficacious
      treatment of psychiatric comorbidity increases the likelihood of seizure freedom
      as well as optimizes psychosocial functioning and quality of life. By contrast,
      failure to treat can allow psychiatric comorbidity to persist or psychological
      difficulties to develop as the patient adjusts to life after surgery.

PMID- 22473540
TI  - ONe More Weapon in the FIght Against Drop Seizures in Lennox-Gastaut Syndrome.

PMID- 22473541
TI  - Two populations are better than one.

PMID- 22473542
TI  - High-frequency oscillations recorded on scalp EEG.

PMID- 22473543
TI  - Hypothalamic hamartomas-what determines seizure types and other clinical
      manifestations?

PMID- 22473544
TI  - It's the Seizures, S#%&*D! The Tragedy of Recurring Seizures in Adults.

PMID- 22473545
TI  - Too Complicated or So Simple: AED Type and AED Dose Matter for Pregnancy.

PMID- 22473546
TI  - Tales of a dirty drug: carbenoxolone, gap junctions, and seizures.

PMID- 22473547
TI  - Brain Autonomous Mechanisms of Seizure-Induced BBB Dysfunction.

PMID- 22473548
TI  - Not RESTing on Its Laurels: Timing and Mechanisms of HCN Channel Dysfunction in
      Epilepsy.

PMID- 22473549
TI  - R U OK? The Novel Therapeutic Potential of R Channels in Epilepsy.

PMID- 22473550
TI  - Dental school faculty perceptions of and attitudes toward the new dental therapy
      model.
AB  - The University of Minnesota School of Dentistry launched its new dental therapy
      program in September 2009 after the Minnesota state legislature had authorized
      the training and practice of a dental therapist in May of the same year. The
      creation of this mid-level dental provider is seen as a workforce solution to
      help address the problem of access to dental care experienced by some members of
      our society. However, there is a lack of consensus and even controversy in
      organized dentistry about dental therapy, one of the mid-level provider models.
      This study explored the attitudes and perceptions of dental school faculty
      members who have been tasked to prepare these new dental therapists to do their
      work. Focus groups were conducted with a randomly selected group of faculty
      members, the results of which were used to develop a survey of faculty members in
      all departments of the school. A total of 151 faculty members responded to the
      survey: 68 percent of these respondents were fifty-one years of age or older; 79
      percent were male; and 39 percent were full-time and 61 percent part-time. Fifty
      four percent were clinical faculty members, and the rest taught in the
      preclinical courses and basic sciences. The study found that these dental faculty
      members believe dentists have a personal responsibility in the care of the
      underserved but do not agree that the dental therapists are part of the solution
      to improve access. There was a clear divide between the part-time faculty
      members, who practice outside the institution, and the full-time educators with
      regard to the role of dental therapists. However, there was an overall consensus
      that dental faculty members have a commitment and responsibility to educate
      future dental therapists regardless of their personal position. This is
      encouraging to dental therapy students, who can be assured that they will receive
      the education they need to prepare them to practice.

PMID- 22473551
TI  - Assessing context effects on test validity of the National Board Dental
      Examination Part I.
AB  - In support of actions taken by the Joint Commission on National Dental
      Examinations, two changes--the inclusion of testlet items and the random
      presentation of items in an interdisciplinary format--were made to enhance the
      test validity of the National Board Dental Examination Part I in 2007. As a
      result, the examination was changed from a conjunctive to a comprehensive format.
      It was assumed that validity would be enhanced with regard to the examination's
      internal structure, while not disturbing item performance and examinee score.
      This study of the results found that 1) three underlying variables were extracted
      from the conjunctive Part I but only two underlying variables from the
      comprehensive Part I and 2) the differences in item performance and examinee
      score were generally small in effect size across formats. Factor analyses
      revealed that Part I was more discipline-sensitive for the conjunctive format but
      more item format-sensitive for the comprehensive format. The revision of Part I
      changed the nature of the examination from a discipline-based format to a more
      clinically relevant, interdisciplinary format, a favorable outcome anticipated by
      the Joint Commission. The results of this study provide evidence supporting the
      validity of the revised Part I examination for its intended purpose in the
      licensure process.

PMID- 22473552
TI  - Typodont versus live patient: predicting dental students' clinical performance.
AB  - In this study, the authors evaluated the accuracy and precision of non-clinical
      testing for dental students' crown preparation proficiency on a manikin-mounted
      typodont as a predictor of performance on patients. Eighty-six seniors at Baylor
      College of Dentistry were evaluated by three calibrated senior faculty members
      from the general dentistry department. Four areas of interest were evaluated:
      occlusal reduction; axial reduction; margins, design, and finish line; and
      operative environment. Standardized grading scales were utilized to evaluate
      these preparation components. The kappa agreement statistic was used to assess
      agreement for the areas, which were then compiled to get an overall performance
      score. A Bland-Altman plot was generated and analyzed for agreement on overall
      performance between typodont and patient. Results of the analyses showed weak
      agreement between the two measurements for all four areas of interest with large
      variation in the differences. When the pairs of overall performance scores were
      compared, the Bland-Altman plot indicated that the typodont composite score was
      often larger than the patient composite score, especially for poorer performing
      students. The authors conclude that students' clinical performance on typodonts
      is a poor predictor of their clinical performance on patients since the students
      performed much worse on the clinical crown examination than on the typodont
      examination.

PMID- 22473553
TI  - Using multiple methods to assess learning and outcomes in an online degree
      granting dental hygiene program.
AB  - Program evaluation is a necessary component of curricular change and innovation.
      It ascertains whether an innovation has met benchmarks and contributes to the
      body of knowledge about educational methodologies and supports the use of
      evidence-based practice in teaching. Education researchers argue that rigorous
      program evaluation should utilize a mixed-method approach, triangulating both
      qualitative and quantitative methods to understand program effectiveness. This
      approach was used to evaluate the University of Michigan Dental Hygiene Degree
      Completion E-Learning (online) Program. Quantitative data included time spent on
      coursework, grades, publications, course evaluation results, and survey
      responses. Qualitative data included student and faculty responses in focus
      groups and on surveys as well as students' portfolio reflections. The results
      showed the program was academically rigorous, fostering students' ability to
      connect theory with practice and apply evidence-based practice principles. These
      results also demonstrated that the students had learned to critically reflect on
      their practice and develop expanded professional identities; going beyond the
      role of clinician, they began to see themselves as educators, advocates, and
      researchers. This evaluation model is easily adaptable and is applicable to any
      health science or other professional degree program. This study also raised
      important questions regarding the effect of meta-reflection on student confidence
      and professional behavior.

PMID- 22473554
TI  - Leveraging the power of Web 2.0 tools: a wiki platform as a multimedia teaching
      and learning environment in dental education.
AB  - This article presents the development and implementation of a wiki-based
      application for the delivery of educational content in dentistry. The Dental
      Procedure Education System (DPES) is a new web application that uses SharePoint
      to combine online collaborative authoring characteristic of wiki spaces with
      instructional video documentaries. Harnessing the wiki's versatility, DPES offers
      faculty members an avenue to develop an authoritative source of information for
      both students, through DPES Pro, and the public at large, through DPES Public.
      Principles of cognitive theory of multimedia learning, constructivist theory, and
      collaborative writing were employed in the development of DPES. An authoring
      protocol, with a clearly defined sequence of steps, was established in order to
      keep the production of the DPES procedures consistent and predictable. Initial,
      anecdotal user reports indicate that DPES is well received among dental students
      and faculty members. Expected outcomes and benefits of DPES use are discussed,
      and directions for research are proposed.

PMID- 22473555
TI  - Predoctoral fixed implant patient satisfaction outcome and challenges of a
      clinical implant competency.
AB  - Treatment with fixed and removable partial dentures has been the traditional
      method of addressing the replacement of teeth competencies in dental education.
      However, by 2013 the Commission on Dental Accreditation (CODA) standards will
      mandate a competency in "replacement of teeth including fixed, removable, and
      dental implants." In 2005, New York University College of Dentistry implemented a
      comprehensive implant program for predoctoral dental students. One of the outcome
      assessments of this program was to determine the level of patient satisfaction.
      Therefore, a patient satisfaction survey (n=103) assessed the use of implant
      treatment for the restoration of partially edentulous patients, measuring such
      dimensions of satisfaction as function, comfort, and esthetics. The results
      revealed that 96 percent of the patients surveyed were satisfied with their
      ability to chew, 91 percent were satisfied with the comfort of their restoration,
      and 86 percent were satisfied with the appearance of their restoration.
      Additionally, 90 percent of the surveyed patients who received implant-retained
      crowns as part of their routine care were satisfied with the overall treatment
      experience, and 97 percent of them would recommend this treatment to a friend.
      The survey results validate implant-supported crown treatment in predoctoral
      education. Although implant-supported restorations are a valid treatment option
      that must be presented to patients during treatment planning, creating a clinical
      competency in implant therapy requires greater consideration. Therefore, the
      benefits and challenges of such a clinical competency are discussed.

PMID- 22473556
TI  - Measuring change in critical thinking skills of dental students educated in a PBL
      curriculum.
AB  - This study measured the change in critical thinking skills of dental students
      educated in a problem-based learning (PBL) pedagogical method. The quantitative
      analysis was focused on measuring students' critical thinking skills achievement
      from their first through third years of dental education at the University of
      Southern California. This non-experimental evaluation was based on a volunteer
      sample of ninety-eight dental students who completed a demographics/academic
      questionnaire and a psychometric assessment known as the Health Sciences
      Reasoning Test (HSRT). The HSRT produced the overall critical thinking skills
      score. Additionally, the HSRT generated five subscale scores: analysis,
      inference, evaluation, deductive reasoning, and inductive reasoning. The results
      of this study concluded that the students showed no continuous and significant
      incremental improvement in their overall critical thinking skills score
      achievement during their PBL-based dental education. Except for the inductive
      reasoning score, this result was very consistent with the four subscale scores.
      Moreover, after performing the statistical adjustment on total score and subscale
      scores, no significant statistical differences were found among the three student
      groups. However, the results of this study found some aspects of critical
      thinking achievements that differed by categories of gender, race, English as
      first language, and education level.

PMID- 22473557
TI  - The endangered clinical teacher-scholar: a promising update from one dental
      school.
AB  - Clinical dental faculty members' lack of scholarly activity not only impacts
      their ability to be promoted and retained in their institutions but limits the
      contributions they could make to clinical discovery. Contributing factors to this
      situation include the lack of purposeful mentoring and the widespread faculty
      shortages, which increase faculty workloads. One way to address this challenge is
      to develop and implement formal mentoring programs, endorsed by the dental
      school's administration, that use reward structures in which novice clinical
      faculty members are teamed with faculty members experienced in scholarly
      activity. The Clinical Research Scholars Program at the University of Pittsburgh
      School of Dental Medicine has been in existence since 2008. Preliminary data from
      this program suggest that this has been a successful plan for increasing the
      scholarly activity of the clinical teacher-scholar. Although not without
      limitations, this program may serve as a model for other schools to consider as
      they encourage their own clinical faculty members to undertake research
      initiatives. Similar programs at dental schools across the country can enhance
      discovery, research, and treatment by expanding the number of researchers who are
      addressing the public's oral and systemic health needs.

PMID- 22473558
TI  - Creating an objective structured teaching examination to evaluate a dental
      faculty development program.
AB  - This article describes the creation of an objective structured teaching
      examination (OSTE) to assess a dental faculty development program. An OSTE is a
      performance-based measure that utilizes standardized students and is designed to
      measure observable teaching skills. In spring 2010, the authors developed,
      implemented, and evaluated an OSTE to assess a New York University College of
      Dentistry (NYUCD) faculty development program, Class ACTS (Advanced Clinical
      Teaching Scholars). They created a three-station OSTE to measure changes in
      teaching skills resulting from participation in Class ACTS. Dental student
      teaching assistants were trained to act as standardized students and patients and
      to use the rating forms. The faculty members' OSTE scores and ratings increased
      after participating in the Class ACTS program in all fifteen teaching domains
      tested, and statistically significant improvements occurred in nine of the
      fifteen domains. A search of the relevant literature suggests that this is the
      first time that an OSTE has been used to assess a faculty development program in
      dental education. This study's results appear to support NYUCD's faculty
      development efforts to improve the teaching skills of its faculty members.

PMID- 22473559
TI  - Improving tobacco dependence education for dental and dental hygiene students at
      Loma Linda University School of Dentistry.
AB  - In a general effort to facilitate dental professionals' effective tobacco
      dependence education (TDE), the student part of the project reported here had
      three purposes: 1) to promote tobacco cessation activities in the dental school
      clinic, 2) to evaluate dental and dental hygiene students' confidence level in
      treating tobacco-dependent patients, and 3) to determine the frequency, duration,
      and depth with which the students assisted tobacco-dependent patients. Surveys of
      senior dental and dental hygiene students at the Loma Linda University School of
      Dentistry were conducted in 2008. Of the twenty-seven questions on the survey,
      nineteen related to the procedures students performed and questions asked of
      patients, one question asked how many minutes students spent counseling patients,
      and seven questions related to barriers to incorporating TDE activities. Only
      56.5 percent of the responding dental students reported they routinely "asked and
      advised" about their patients' smoking behaviors, but 87.5 percent of the
      responding dental hygiene students reported they routinely did so. After the
      curricular intervention, the follow-up survey found that the dental students more
      frequently showed their patients the effects of tobacco on the oral mucosa and
      more frequently discussed pharmacotherapy options and made referrals during
      routine care. Until all dental and dental hygiene students are required to meet
      written board and clinical competencies in TDE and given adequate mentoring by
      clinical faculty to treat tobacco-dependent patients, the likelihood of seeing
      major improvements in tobacco-cessation treatment in dental practices is low.

PMID- 22473560
TI  - Dental students and bloodborne pathogens: occupational exposures, knowledge, and
      attitudes.
AB  - Dental professionals may be exposed to bloodborne pathogens in their work, and
      dental students may be a particularly vulnerable group. Fear of exposure has also
      been linked to discriminatory practices. A cross-sectional survey of dental
      students was conducted at one U.S. dental school to assess their knowledge about
      the transmission of bloodborne pathogens and management of exposures; the
      frequency of their bloodborne pathogen exposures (BBPEs); and associations among
      their prior exposure, knowledge, perception of knowledge, and attitudes toward
      practice. Overall, 220 students (72.1 percent) responded to the survey, and 215
      (70.5 percent) answered questions about exposures. The prevalence of BBPE was
      19.1 percent and was greater among clinical than preclinical students (p<0.01).
      Percutaneous injuries occurred in 87.5 percent of those exposed. All students
      (preclinical and clinical combined) answered more survey questions correctly
      about transmission of bloodborne pathogens (66.7 percent) than about post
      exposure management (25.0 percent). Fewer than half reported adequate knowledge
      of transmission and management (47.5 percent and 37.3 percent, respectively). In
      this context, 8.2 percent of the respondents acknowledged an unwillingness to
      perform procedures on patients with HIV. Since knowledge gaps may lead to failure
      to report incidents and delays in appropriate exposure management and some
      negative attitudes towards treating individuals with HIV persist, these findings
      justify improving BBPE education at U.S. dental schools.

PMID- 22473561
TI  - The dental school learning milieu: students' perceptions at five academic dental
      institutions in Pakistan.
AB  - The significance of the educational environment in health professions academic
      institutions, increasingly recognized on a global scale, is fundamental to
      effective student learning. This study was carried out to evaluate students'
      perceptions of the educational environment in five undergraduate dental
      institutions in Pakistan. This non-interventional study used a postal
      questionnaire based on the Dundee Ready Educational Environment Measure (DREEM).
      The subjects were dental students taking the final professional B.D.S.
      examination at five dental institutions affiliated with the University of Health
      Sciences, Lahore, Pakistan. A total of 197 students participated in the study
      (response rate of 83.82 percent). The overall DREEM score was 115.06 (Cronbach's
      alpha 0.87). Nine items recorded scores <2 and were flagged for remediation.
      Significant differences were observed between students' perceptions of learning
      and of teachers (p<0.05). Many issues challenge the quality and delivery of
      dental education in Pakistan, and dental institutions need to develop robust
      mechanisms to incorporate contemporary international trends in dental education
      in order to improve the educational environment.

PMID- 22473562
TI  - Dental students' knowledge of and attitudes toward anticoagulation dental
      treatment: assessment of a one-day course at the University of Murcia, Spain.
AB  - The aim of this study was to determine a group of Spanish dental students'
      knowledge of and attitudes toward anticoagulated patients and clinical practice
      and to assess the need for additional education in this area. A survey with
      sections on demographics and knowledge of general coagulation, anticoagulation
      treatment, clinical practice, local hemostatic measures, and antibiotic
      prophylaxis was distributed to students before and after a one-day course on oral
      anticoagulation. The response rate was 67.1 percent (n=96). Of the respondents,
      78.1 percent (seventy-five) were women. The students who benefited most from the
      course were third-year students since they had the lowest level of knowledge at
      the beginning of the course (p>0.05). Fifth-year students and postgraduates had a
      good initial level of knowledge (87 percent). This study identified a lack of
      knowledge among this group of Spanish dental students prior to the course, but
      participating in the course led to considerable improvement.

PMID- 22473563
TI  - Continuous assessment of undergraduate students at a dental college in India.
AB  - The purpose of this retrospective study was to evaluate the quantitative
      assessment of a structured essay and standardized oral examination and its
      correlation to the final-year graduating exam in the Department of Pediatric
      Dentistry, Meenakshi Ammal Dental College and Hospital, Chennai, India. The
      records of 531 students from 2005 to 2009 were collected. Students were
      categorized based on their "completion" and "grading" in a structured essay and
      standardized oral examination, which is a continuous assessment of dental
      students in the college. The grades obtained by continuous assessment were
      compared to students' final-year examination scores. The assessment showed that
      students who completed all tasks and had desirable performance in their written
      assessment and standardized oral examination also scored better on their final
      examination. Therefore, the continuous assessment by written assessment and
      standardized oral examination had a direct relationship to students' performance
      on the final examination and is useful for evaluation.

PMID- 22473564
TI  - Root canal shaping using rotary nickel-titanium files in preclinical dental
      education in Turkey.
AB  - The purposes of this study were to evaluate the ability of a group of third-year
      dental students without any endodontic clinical experience to use the ProTaper
      Instruments (Dentsply Maillefer) to decrease the amount of straightening of
      curved canals on human molar teeth and to determine the incidence of instrument
      fractures and instrumentation time. Thirty-one undergraduate dental students in
      Turkey received a training session. The students prepared a total of 144 root
      canals in human mandibular or maxillary molar teeth with ProTaper. Fifty-six
      teeth were excluded due to unreadable image, misinformation, or straight or
      severe curve. Using pre- and post-preparation digital radiographs, the
      straightening of curved root canals was investigated. Loss of working length and
      incidence of fracture were also noted. A total of eighty-eight curved root canals
      were selected. Mesiobuccal or mesiolingual roots with curvatures of between 20
      degrees  and 43 degrees  as assessed by Schneider's method and working length of
      between 15 mm and 22.5 mm were included in the study. The means of the curved
      root canals before and after the instrumentation were 29.5 degrees  +/- 6 degrees
      and 27 degrees  +/- 6.3 degrees , respectively. The means of the working length
      before and after the instrumentation were 19 mm +/- 2.1 mm and 18.3 mm +/- 1.9
      mm, respectively. A statistically significant difference between straightening of
      curved root canals and loss of working length was found between before and after
      instrumentation (p<0.000). The mean straightening of curved root canals and loss
      of working length after preparation with the size F1 ProTaper file were 2.5 mm +/
      3.6 mm and 0.7 mm +/- 0.6 mm, respectively. Only two F1 ProTaper instruments
      fractured at the apical level. The study concluded that rotary instruments
      performed adequately with inexperienced operators who received a brief structured
      training session.

PMID- 22473567
TI  - An unprecedented AB2 tetrahedra network structure type in a high-pressure phase
      of phosphorus oxonitride (PON).

PMID- 22473565
TI  - A versatile enantioselective synthesis of azabicyclic ring systems: a concise
      total synthesis of (+)-grandisine D and unnatural analogues.
AB  - Closing in on azacines: We have developed a new six step approach for the rapid
      and enantioselective synthesis of indolizidine, pyrrolo[1,2-a]azepine, and
      pyrrolo[1,2-a]azocine azabicyclic systems and their respective lactam congeners,
      which are found in a host of natural products as well as pharmaceutical
      preparations. This protocol enables a concise enantioselective total synthesis of
      (+)-grandisine D in 16.4 % overall yield from commercial materials (see scheme).

PMID- 22473568
TI  - Urodynamic features and artefacts.
AB  - AIMS: The aims of this study are to compile a list of common features and
      artefacts found in urodynamics, to produce definitions of these features, and
      describe any necessary remedial action. An image and word description for each
      event has been included as well as statistics providing information on the
      prevalence and frequency of each event. METHODS: In order to identify the most
      common features and artefacts 200 consecutive urodynamic traces were reviewed. A
      random 10% sample was cross-checked to ensure event classification accuracy. To
      extract significant pressure peaks from the data, an algorithm was written
      capable of detecting initial resting pressure and updating it as necessary.
      Significant pressure peaks were defined as those that differed from resting
      pressure values by 10 cmH(2) O or more. When describing the events, standard
      sources were consulted for published definitions. The images selected for each
      event are typical examples but do not represent the variation that can occur
      between examples. The patients whose files were used in this study suffered from
      a variety of lower urinary tract disorders so that it is likely that they cover
      all common or important urodynamic pressure events. RESULTS: In total 10,355
      pressure events were identified and classified into 19 different categories. For
      each category, a description, example image and remedial action are included.
      Where published definitions do not exist, new ones are proposed. CONCLUSIONS: All
      common or important urodynamic pressure events have been included in this study
      and descriptions of the events have been included in one article for the first
      time.

PMID- 22473569
TI  - Bidirectional esophageal dilatation in pharyngoesophageal stenosis
      postradiotherapy.
AB  - Severely stenosed radiation-induced benign strictures around the level of
      cricopharyngeus post-radical chemoradiation for head and neck or upper esophageal
      cancers pose significant management problems. We report our technique of
      bidirectional assessment and dilatation of pharyngoesophageal strictures in
      patients with an in situ percutaneous endoscopic gastrostomy (PEG) tube. The
      upper gastrointestinal surgeon approached the area of stenosis in a retrograde
      manner through the PEG tube to guide the otolaryngeal surgeon who performed
      anterograde dilatation via a rigid laryngoscope. Between 2005 and 2009,
      bidirectional esophageal dilatation was performed on 5 patients at our
      institution. Video fluoroscopy confirmed improved patency of stenosed esophagus
      in all cases and good improvement in swallowing ability in 4 patients. The
      ability to accurately assess pharyngoesophageal strictures using bidirectional
      visualization and transillumination is the key modification of our technique. We
      suggest using bidirectional esophageal dilatation on difficult cases with severe
      pharyngoesophageal stenoses although extreme care is required.

PMID- 22473570
TI  - Facile method for rGO field effect transistor: selective adsorption of rGO on SAM
      treated gold electrode by electrostatic attraction.
AB  - A facile method for the fabrication of negatively and positively charged rGO
      field effect transistors (FETs) is proposed, which utilizes electrostatic
      attraction between electrodes and rGO sheets. Negatively and positively charged
      rGO sheets are functionalized with carboxylic acid and amine groups,
      respectively. The FET of amine-functionalized rGO exhibits an n-doping effect.
      The FET devices fabricated by this method show high mobility of carriers.

PMID- 22473571
TI  - The literature on inhibitors: articles that influence my management of patients
      with hemophilia A and high-titer inhibitors.
AB  - High-titer inhibitors represent the greatest management challenge faced by
      clinicians who treat patients with hemophilia A, as bleeding episodes no longer
      respond to standard factor VIII replacement therapy. Over the last seven decades,
      major strides have been made in inhibitor treatment. This article focuses on the
      seminal clinical observations and studies that provided the foundation for these
      advances in hemophilia care.

PMID- 22473572
TI  - Synthesis of 1,2,4-triazines and the triazinoisoquinolinedione DEF ring system of
      noelaquinone.
AB  - The intramolecular Staudinger-aza-Wittig reaction is used for a general synthesis
      of 1,2,5,6-tetrahydro-1,2,4-triazines, a structural motif reported for the
      natural product noelaquinone. The DEF moiety of noelaquinone was obtained in 13
      steps and 2% overall yield, and the structure of the synthetic product was
      confirmed by X-ray analysis.

PMID- 22473573
TI  - Recent advances in solar cells based on one-dimensional nanostructure arrays.
AB  - As the demand for renewable energy resource is growing rapidly worldwide, a
      variety of energy materials and technologies are being developed. In this review,
      we aim to summarize recent developments in the state-of-the-art research on
      energy harvesting technologies such as thin-film Si or Ge, CdTe, GaAs, organic,
      hybrid, and dye-sensitized solar cells (DSSCs) utilizing one-dimensional (1D)
      nanomaterials, mainly semiconductor nanowires, nanocones, nanotubes and
      nanofibers, which are prepared by vapor-liquid-solid method, colloidal
      lithography, template-guided growth, or electrospinning. Moreover, the future
      challenges (such as efficiency improvement and natural resource limitations) and
      prospects of nanostructured solar cells are proposed.

PMID- 22473575
TI  - Clinicopathological characteristics and prognosis of patients with esophageal
      carcinoma invading adjacent structures found during esophagectomy.
AB  - OBJECTIVES: A treatment strategy for patients with esophageal carcinoma invading
      adjacent structures found during esophagectomy (surgical T4; sT4) has not been
      established and the role of esophagectomy remains controversial. The aims of this
      study were to assess the clinicopathological characteristics and to clarify the
      prognostic factors of patients who underwent esophagectomy for sT4 tumors.
      METHODS: A consecutive series of 76 patients who were found to have sT4 tumors
      was reviewed retrospectively. T4 tumors were divided into two groups according to
      the invaded structures. Cox's multivariate proportional hazard model was used to
      identify prognostic factors. RESULTS: Complete tumor clearance with combined
      resection was performed in 12 patients (16%). Overall 1-, 3-, and 5-year survival
      rates were 40.8%, 9.2%, and 7.9%, respectively. There was no significant
      relationship between survival and invaded structure type or residual tumor
      status. Postoperative therapy was selected as an independent prognostic factor.
      CONCLUSIONS: The complete resection rate was low and the prognosis of patients
      with sT4 tumors was poor. Subclassification according to the invaded structures
      was not a prognostic factor in this study. Postoperative therapy may improve
      survival in sT4 patients and should be considered irrespective of residual tumor
      status after esophagectomy.

PMID- 22473576
TI  - Advanced endoscopic imaging using narrow-band imaging for diagnosis     of
      Whipple's disease.

PMID- 22473577
TI  - Primary combined adenoid cystic carcinoma, basaloid squamous cell     carcinoma,
      and squamous cell carcinoma of the esophagus.

PMID- 22473578
TI  - Secondary aortoduodenal fistula in the duodenal bulb: role of     side-viewing
      endoscopy.

PMID- 22473579
TI  - Splenic artery pseudoaneurysm treated with thrombin injection     guided by
      endoscopic ultrasound.

PMID- 22473580
TI  - Risk factors associated with asthma phenotypes in dental healthcare workers.
AB  - BACKGROUND: Exposure in the dental environment can increase the risk of
      respiratory disease in dental healthcare workers (HCWs). This study investigated
      the prevalence of asthma phenotypes in dental HCWs and associated risk factors.
      METHODS: A cross-sectional study of 454 dental HCWs in five dental institutions
      in South Africa was conducted. A self-administered questionnaire elicited the
      health and employment history of subjects. Sera was analyzed for atopic status
      and latex sensitization. Pre- and post-bronchodilator spirometry was performed.
      RESULTS: The prevalence of atopic asthma was 6.9%, non-atopic asthma 5.9% and
      work-exacerbated asthma (WEA) 4.0%. Atopy and work-related ocular-nasal symptoms
      were strong predictors of WEA (OR: 3.4; 95% CI: 1.07-10.8; OR: 6.7, 95% CI: 2.4
      19.1), respectively. Regular use of personal protective equipment (PPE) was
      associated with a protective affect (OR: 0.23, 95% CI: 0.1-0.7) among non-atopic
      asthmatics, while glove use and respiratory protection was protective among
      atopic asthmatics (OR: 0.39, 95% CI: 0.17-0.89). CONCLUSION: Identification of
      risk factors associated with specific asthma phenotypes in dental HCWs can be
      used to focus preventive strategies for asthmatics.

PMID- 22473581
TI  - Pyrrole aminoimidazole alkaloid metabiosynthesis with marine sponges Agelas
      conifera and Stylissa caribica.
AB  - Game-SET-match: Pyrrole aminoimidazole alkaloids (PAIs) are metabiosynthesized
      from chlorinated analogues of oroidin by cell-free enzyme preparations from PAI
      producing sponges. Evidence and implications for the biosynthesis of PAIs include
      putative single-electron transfers (SETs) that promote C-C bond-forming reactions
      of precursors.

PMID- 22473583
TI  - Gold- and platinum-bismuth donor-acceptor interactions supported by an ambiphilic
      PBiP pincer ligand.
AB  - Noble metals meet a heavyweight: A pincer ligand brings together bismuth with
      gold and platinum, so that metallophilic interactions are established. According
      to DFT calculations, these interactions contain dominant metal->bismuth
      contributions.

PMID- 22473584
TI  - PdM (M = Pt, Au) bimetallic alloy nanowires with enhanced electrocatalytic
      activity for electro-oxidation of small molecules.
AB  - A facile and general method has been developed to synthesize well-defined PdPt
      and PdAu alloy nanowires, which exhibit significantly enhanced activity towards
      small molecules, such as ethanol, methanol, and glucose electro-oxidation in an
      alkaline medium. Considering the important role of one-dimensional alloy
      nanowires in electrocatalytic systems, the present Pd-based alloy nanostructures
      could offer a promising new class of advanced electrocatalysts for direct alcohol
      fuel cells and electrochemical sensors.

PMID- 22473585
TI  - Long-term local area employment rates as predictors of individual mortality and
      morbidity: a prospective study in England, spanning more than two decades.
AB  - BACKGROUND: Although long-term trends in local labour market conditions are
      likely to influence health, few studies have assessed whether this is so. This
      paper examines whether (1) trends in local employment rates have relevance for
      mortality and morbidity outcomes in England and (2) trends are stronger
      predictors of these outcomes than employment rates measured at one point in time.
      METHODS: Using latent class growth models, local areas were classified into eight
      groups following distinct trends in employment rates between 1981 and 2008. Areas
      were also categorised in 'octile' groups by rank of employment rates in 2001.
      These area groupings were linked to a sample of 207,959 individuals from the
      Office of National Statistics Longitudinal Study. Associations between area
      groupings and risk of all-cause mortality and of reporting a limiting long-term
      illness at the end of the period were measured using logistic regression. Models
      were adjusted for individuals' socio-demographic characteristics measured in 1981
      and for their residential mobility between 1981 and 2001. RESULTS: Compared to
      areas with continuously high employment rates over the period, risk of mortality
      and morbidity was higher in areas with persistently low or declining employment
      rates. Findings suggest that long-term trends in local employment rates are
      useful as predictors of mortality and morbidity differences. These are not so
      clearly distinguished by only considering employment rates at one point in time.
      CONCLUSION: Poor health outcomes are associated with long-term economic
      disadvantage in some areas of England, reflected in employment rates, underlining
      the importance of efforts to improve health in areas with especially 'deep
      seated' deprivation.

PMID- 22473586
TI  - Controversy over bird flu.

PMID- 22473587
TI  - Chronic eosinophilic leukemia-not otherwise specified has a poor prognosis with
      unresponsiveness to conventional treatment and high risk of acute transformation.
AB  - Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare
      disorder with hypereosinophilia and an increased number of blood or marrow blast
      (<20%) or an evidence of eosinophil clonality.We evaluated the clinical outcome
      of 10 patients with CEL-NOS. Seven males and three females at a median age of 62
      years (range, 23-73) were included. The median leukocyte count at diagnosis was
      33.4 3109/l (range, 9.3-175.0) with a median eosinophil count of 15.6 3 109/l
      (range, 1.5-136.0). Median hemoglobin and platelets were 11.0 g/dl (range, 8.3
      13.3) and 158 3 109/l (range, 31.0-891.0), respectively. Clinical manifestations
      included splenomegaly (n 5 7), hepatomegaly (n 56), cardiac failure (n 5 2), and
      lung infiltrations (n 5 1). Median survival from diagnosis to death for entire
      cohort was 22.2 months (range,2.2-186.2). Five of the 10 studied patients
      developed acute transformation(AT) after median of 20 months from diagnosis
      (range, 1.6-41.9).None of patients with AT is alive at the time of last follow
      up. Median time from AT to death was 2 months (range, 1.0-6.1). Among five
      patients who did not develop AT, three died in active disease. Two patients are
      alive in complete remission; first underwent allogeneic stem-cell transplantation
      preceding by intensive induction chemotherapy;the second remains on imatinib with
      hydroxyurea. Except the latter patient, imatinib was ineffective in our study
      population. CEL-NOS is a rare and aggressive disease with high rate of AT and
      resistance to conventional treatment.

PMID- 22473589
TI  - Effects of specific adsorption on the differential capacitance of imidazolium
      based ionic liquid electrolytes.

PMID- 22473590
TI  - A zwitterion-DNA coating stabilizes nanoparticles against Mg2+ driven aggregation
      enabling attachment to DNA nanoassemblies.
AB  - Plasmonics and photonics demand new methods for the controlled construction of
      nanoparticle (NP) arrays. Complex, low-symmetry configurations of DNA
      functionalized NPs are obtained by connection to scaffolds of branched and folded
      DNA nanostructures. However, the stabilization of these branched structures by
      Mg(2+) counterions also drives the uncontrolled aggregation of NPs. We
      demonstrate, using a two-dimensional DNA scaffold, that derivatizing gold
      nanoparticles (AuNPs) with zwitterionic ligands overcomes this problem.

PMID- 22473592
TI  - Phase II study of everolimus in patients with locally advanced or metastatic
      transitional cell carcinoma of the urothelial tract: clinical activity, molecular
      response, and biomarkers.
AB  - BACKGROUND: This phase II study assessed the safety and efficacy of everolimus,
      an oral mammalian target of rapamycin inhibitor in advanced transitional
      carcinoma cell (TCC) after failure of platinum-based therapy. PATIENTS AND
      METHODS: Thirty-seven patients with advanced TCC received everolimus 10 mg/day
      until progressive disease (PD) or unacceptable toxicity. The primary end point
      was the disease control rate (DCR), defined as either stable disease (SD),
      partial response (PR), or complete response at 8 weeks. Angiogenesis-related
      proteins were detected in plasma and changes during everolimus treatment were
      analyzed. PTEN expression and PIK3CA mutations were correlated to disease
      control. RESULTS: Two confirmed PR and eight SD were observed, resulting in a DCR
      of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with
      noncontrolled disease, we observed in patients with controlled disease a
      significant higher baseline level of angiopoietin-1 and a significant early
      plasma decrease in angiopoietin-1, endoglin, and platelet-derived growth factor
      AB. PTEN loss was observed only in patients with PD. CONCLUSIONS: Everolimus
      showed clinical activity in advanced TCC. The profile of the plasma angiogenesis
      related proteins suggested a role of the everolimus antiangiogenic properties in
      disease control. PTEN loss might be associated with everolimus resistance.

PMID- 22473593
TI  - Prognosis after high-dose chemotherapy followed by autologous stem-cell
      transplantation as first-line treatment in primary CNS lymphoma--a long-term
      follow-up study.
AB  - BACKGROUND: High-dose chemotherapy followed by autologous stem-cell
      transplantation (HCT-ASCT) is a promising approach in eligible patients with
      primary central nervous system lymphoma (PCNSL). We report long-term data of
      patients who were treated according to HCT-ASCT containing protocols. PATIENTS
      AND METHODS: We analyzed survival and relapse rates in 43 (<67 years)
      immunocompetent patients with newly diagnosed PCNSL being treated according to
      two different high-dose methotrexate-based protocols followed by high-dose
      carmustine/thiotepa (BCNU/TT) plus ASCT (+/-whole brain irradiation). Analysis
      was conducted for all patients (intention-to-treat) and those patients who
      actually received HCT-ASCT (per-protocol). RESULTS: Thirty-four patients achieved
      complete remission, of those 12 relapsed (35%), while 6 of them relapsed 5 years
      after diagnosis. After a median follow-up of 120 months, median overall survival
      (OS) was reached after 104 months. Two- and 5-year OS was 81% and 70% and 2- and
      5-year event-free survival (EFS) was 81% and 67%, respectively. In per-protocol
      analysis (N = 34), 5-year OS and EFS was 82% and 79%, respectively. HCT-ASCT
      associated related mortality was not observed. CONCLUSIONS: Sequential high-dose
      MTX containing chemotherapy followed by high-dose carmustine/thiotepa plus ASCT
      (+/-whole brain irradiation) is safe and leads to high survival rates in eligible
      patients with newly diagnosed PCNSL.

PMID- 22473594
TI  - Clinical biopsychosocial risk factors for depression in lung cancer patients: a
      comprehensive analysis using data from the Lung Cancer Database Project.
AB  - BACKGROUND: Various risk factors for depression in lung cancer patients have been
      suggested but have been examined separately in studies with relatively small
      sample sizes. The present study examined the biopsychosocial risk factors of
      depression in lung cancer patients, focusing on psychological factors in the
      largest patient sample reported to date. PATIENTS AND METHODS: A total of 1334
      consecutively recruited lung cancer patients were selected, and data on cancer
      related variables, personal characteristics, health behaviors, physical symptoms,
      and psychological factors were obtained. The participants were divided into
      groups with or without depression using the Hospital Anxiety and Depression
      Scale. RESULTS: Among the recruited patients, 165 (12.4%) manifested depression.
      The results of a binary logistic regression analysis were significant (overall
      R2, 36.5%), and a greater risk for depression was strongly associated with
      psychological factors, such as personality characteristics (neuroticism) and
      coping style (low fighting spirit, helplessness/hopelessness, and anxious
      preoccupation). Although the contributions of cancer-related variables, personal
      characteristics, health behaviors, and clinical state were relatively low, cancer
      stage, cancer type, sex, and age correlated significantly with depression.
      CONCLUSION: Depression was most strongly linked with personality traits and
      coping style, and using screening instruments to identify these factors may be
      useful for preventive interventions.

PMID- 22473595
TI  - Cancer of unknown primary (CUP): does cause of death and family history implicate
      hidden phenotypically changed primaries?
AB  - BACKGROUND: Cancer of unknown primary (CUP) is diagnosed at the metastatic stage.
      We aimed to identify hidden primary cancers in CUP patients by comparison with
      cancers in family members. We take use of the fact that the cause of death in CUP
      patients is often coded as the cancer in the organ of fatal metastasis. PATIENTS
      AND METHODS: Forty-one thousand five hundred and twenty-three CUP patients were
      identified in the Swedish Family-Cancer Database, and relative risks (RRs) were
      calculated for cancer in offspring when family members were diagnosed with CUP
      and died of the cancer diagnosed in offspring. RESULTS: The RR for lung cancer in
      offspring was 1.85 when a family member was diagnosed with CUP and died of lung
      cancer. Significant familial associations were found for seven other cancers.
      Many familial associations were also significant when offspring CUP patients died
      of the cancer diagnosed in family members. CONCLUSIONS: The cause of death after
      CUP diagnosis frequently matched the cancer found in a family member, suggesting
      that the CUP had originated in that tissue. The metastasis had probably undergone
      a phenotypic change, complicating pathological tissue assignment. These novel
      data suggest that some CUP cases are phenotypically modified primary cancers
      rather than cancers of unknown primaries.

PMID- 22473596
TI  - Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated
      patients.
AB  - BACKGROUND: Patients with active cancer are often on chronic anticoagulation and
      frequently require interruption of this treatment for invasive procedures. The
      impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not
      known. PATIENTS AND METHODS: Two thousand one hundred and eighty-two consecutive
      patients referred for periprocedural anticoagulation (2484 procedures) using a
      standardized protocol were followed forward in time to estimate the 3-month
      incidence of TE, major bleeding and survival stratified by anticoagulation
      indication. For each indication, we tested active cancer and bridging heparin
      therapy as potential predictors of TE and major bleeding. RESULTS: Compared with
      patients without cancer, active cancer patients (n=493) had more venous
      thromboembolism (VTE) complications (1.2% versus 0.2%; P=0.001), major bleeding
      (3.4% versus 1.7%; P=0.02) and reduced survival (95% versus 99%; P<0.001). Among
      active cancer patients, only those chronically anticoagulated for VTE had higher
      rates of periprocedural VTE (2% versus 0.16%; P=0.002) and major bleeding (3.7%
      versus 0.6%; P<0.001). Bridging with heparin increased the rate of major bleeding
      in cancer patients (5% versus 1%; P=0.03) without impacting the VTE rate (0.7%
      versus 1.4%, P=0.50). CONCLUSIONS: Cancer patients anticoagulated for VTE
      experience higher rates of periprocedural VTE and major bleeding. Periprocedural
      anticoagulation for these patients requires particular attention to reduce these
      complications.

PMID- 22473597
TI  - Adrenocortical carcinoma: past, present, and future.
AB  - Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Due to its rarity,
      heterogeneity, and a lack of a comprehensive understanding of the pathogenesis,
      little progress has been made in treatment and outcomes. The current review
      explores the past, present, and future of the understanding and treatment of this
      disease process.

PMID- 22473598
TI  - Pacific island 'Awa (Kava) extracts, but not isolated kavalactones, promote
      proinflammatory responses in model mast cells.
AB  - Kava ('Awa) is a traditional water-based beverage in Pacific island communities,
      prepared from the ground root and stems of Piper methysticum. Kava use is
      associated with an ichthyotic dermatitis and delayed type hypersensitivity
      reactions. In the current study we collated preparative methodologies from
      cultural practitioners and recreational kava users in various Pacific
      communities. We standardized culturally informed aqueous extraction methods and
      prepared extracts that were subjected to basic physicochemical analysis. Mast
      cells exposed to these extracts displayed robust intracellular free calcium
      responses, and concomitant release of proinflammatory mediators. In contrast,
      mast cells were refractory to single or combinatorial stimulation with
      kavalactones, including methysticin, dihydromethysticin and kavain. Moreover, we
      reproduced a traditional modification of the kava preparation methodology, pre
      mixing with the mucilage of Hibiscus tiliaceus, and observed its potentiating
      effect on the activity of aqueous extracts in mast cells. Taken together, these
      data indicate that water extractable active ingredients may play a role in the
      physiological and pathophysiological effects of kava, and suggests that mast cell
      activation may be a mechanistic component of kava-related skin inflammations.

PMID- 22473599
TI  - Amino acids for Diels-Alder reactions in living cells.

PMID- 22473600
TI  - Attenuation of vagal recovery during sleep and reduction of cortisol/melatonin
      ratio in late afternoon associate with prolonged daytime sleepiness among media
      workers with irregular shift work.
AB  - BACKGROUND: Media work is characterized by information flow, deadlines, and 24/7
      alertness. Good recovery prevents stress-related disorders. METHODS: The
      standardized questionnaire included items about health, health habits, sleep,
      work conditions, and work stress. Recordings of 24-hr heart rate variability
      (HRV) and four salivary samples for cortisol and melatonin levels were analyzed
      from 70 randomly selected workers with irregular shift work, and 70 workers with
      normal daytime work. RESULTS: Irregular shift work increased the risk of
      insufficient recovery when compared to normal daytime work (OR 2.0; P < 0.05). In
      the group of workers with insufficient subjective recovery, HRV was attenuated (P
      < 0.05) during the early hours of night, and cortisol/melatonin ratio was
      decreased (P < 0.05) in the afternoon. CONCLUSIONS: Physiological changes
      underlying subjective feelings of insufficient recovery are measurable.
      Attenuated HRV during sleep reflects prolonged sympathetic drive and/or impaired
      parasympathetic recovery. Interactions between cortisol and melatonin hormones
      might be involved in the development of chronic exhaustion.

PMID- 22473601
TI  - Assessment of donor site morbidity for free radial forearm osteocutaneous flaps.
AB  - PURPOSE: Assessment of donor site morbidity and recipient site complications
      following free radial forearm osteocutaneous flap (FRFOCF) harvest and evaluation
      of patient perceived upper limb disability for free radial forearm osteocutaneous
      versus fasciocutaneous flaps (FRFF). METHODS: First a case series was undertaken
      of 218 patients who underwent an FRFOCF at two tertiary referral centers between
      February 1998 and November 2010. Outcomes included forearm donor site morbidity
      and recipient site complications. Second, the disability of the arm, shoulder,
      and hand (DASH) questionnaire assessing patient perceived arm disability was
      administered by phone to 60 consecutive patients who underwent an FRFOCF or FRFF.
      RESULTS: Mean patient age was 63 years with male predominance (62.8%). Median
      bone length harvested was 8 cm (range, 3-12 cm) with prophylactic plating of the
      radius following harvest. Donor site morbidity included fracture (1 patient,
      0.5%) and sensory neuropathy (5 patients, 2.3%). Mean DASH scores were
      comparative between groups and to established normative values. Mandibular
      malunion rate was 3.2% and hardware extrusion at the recipient site occurred in
      15.6%. CONCLUSION: Reluctance to perform FRFOCF by surgeons usually centers on
      concerns regarding potential donor site morbidity and adequacy of available bone
      stock; however, we identified minimal objective or patient perceived donor site
      morbidity or recipient site complications following harvest of FRFOCFs. Mild
      wrist weakness and stiffness are common but do not impede ability to perform
      activities of daily living. Data from this and other reports suggest this flap is
      particularly useful for midfacial and short segment mandibular reconstruction.

PMID- 22473602
TI  - Involvement of mismatch repair in the reciprocal control of motility and
      adherence of uropathogenic Escherichia coli.
AB  - Type 1 fimbriae and flagella, two surface organelles critical for colonization of
      the urinary tract by uropathogenic Escherichia coli (UPEC), mediate opposing
      virulence objectives. Type 1 fimbriae facilitate adhesion to mucosal cells and
      promote bacterial persistence in the urinary tract, while flagella propel
      bacteria through urine and along mucous layers during ascension to the upper
      urinary tract. Using a transposon screen of the E. coli CFT073 fim locked-ON (L
      ON) mutant, a construct that constitutively expresses type 1 fimbriae and
      represses motility, we identified six mutants that exhibited a partial
      restoration of motility. Among these six mutated genes was mutS, which encodes a
      component of the methyl-directed mismatch repair (MMR) system. When complemented
      with mutS in trans, motility was again repressed. To determine whether the MMR
      system, in general, is involved in this reciprocal control, we characterized the
      effects of gene deletions of other MMR components on UPEC motility. Isogenic
      deletions of mutS, mutH, and mutL were constructed in both wild-type CFT073 and
      fim L-ON backgrounds. All MMR mutants showed an increase in motility in the wild
      type background, and DeltamutH and DeltamutS mutations increased motility in the
      fim L-ON background. Cochallenge of the wild-type strain with an MMR-defective
      strain showed a subtle but significant competitive advantage in the bladder and
      spleen for the MMR mutant using the murine model of ascending urinary tract
      infection after 48 h. Our findings demonstrate that the MMR system generally
      affects the reciprocal regulation of motility and adherence and thus could
      contribute to UPEC pathogenesis during urinary tract infections.

PMID- 22473603
TI  - Contribution of Bordetella filamentous hemagglutinin and adenylate cyclase toxin
      to suppression and evasion of interleukin-17-mediated inflammation.
AB  - Bordetella pertussis and Bordetella bronchiseptica establish respiratory
      infections with notorious efficiency. Our previous studies showed that the fhaB
      genes of B. pertussis and B. bronchiseptica, which encode filamentous
      hemagglutinin (FHA), are functionally interchangeable and provided evidence that
      FHA-deficient B. bronchiseptica induces more inflammation in the lungs of mice
      than wild-type B. bronchiseptica. We show here that the robust inflammatory
      response to FHA-deficient B. bronchiseptica is characterized by the early and
      sustained influx of interleukin-17 (IL-17)-positive neutrophils and macrophages
      and, at 72 h postinoculation, IL-17-positive CD4(+) T cells, suggesting that FHA
      allows the bacteria to suppress the development of an IL-17-mediated inflammatory
      response. We also show that the cyaA genes of B. pertussis and B. bronchiseptica,
      which encode adenylate cyclase toxin (ACT), are functionally interchangeable and
      that ACT, specifically its catalytic activity, is required for B. bronchiseptica
      to resist phagocytic clearance but is neither required for nor inhibitory of the
      induction of inflammation if bacteria are present in numbers sufficient to
      persist during the first 3 days postinoculation. Incubation of bone marrow
      derived macrophages with a DeltacyaA strain caused decreased production of IL
      1beta and increased production of tumor necrosis factor alpha (TNF-alpha) and IL
      12, while incubation with a DeltacyaA DeltafhaB strain caused increased
      production of IL-23. These data suggest that FHA and ACT both contribute to
      suppress the recruitment of neutrophils and the development of an IL-17-mediated
      immune response. To our knowledge, this is the first demonstration of a microbial
      pathogen suppressing IL-17-mediated inflammation in vivo as a strategy to evade
      innate immunity.

PMID- 22473604
TI  - Coxiella burnetii alters cyclic AMP-dependent protein kinase signaling during
      growth in macrophages.
AB  - Coxiella burnetii is the bacterial agent of human Q fever, an acute, flu-like
      illness that can present as chronic endocarditis in immunocompromised
      individuals. Following aerosol-mediated transmission, C. burnetii replicates in
      alveolar macrophages in a unique phagolysosome-like parasitophorous vacuole (PV)
      required for survival. The mechanisms of C. burnetii intracellular survival are
      poorly defined and a recent Q fever outbreak in the Netherlands emphasizes the
      need for better understanding this unique host-pathogen interaction. We recently
      demonstrated that inhibition of host cyclic AMP-dependent protein kinase (PKA)
      activity negatively impacts PV formation. In the current study, we confirmed PKA
      involvement in PV biogenesis and probed the role of PKA signaling during C.
      burnetii infection of macrophages. Using PKA-specific inhibitors, we found the
      kinase was needed for biogenesis of prototypical PV and C. burnetii replication.
      PKA and downstream targets were differentially phosphorylated throughout
      infection, suggesting prolonged regulation of the pathway. Importantly, the
      pathogen actively triggered PKA activation, which was also required for PV
      formation by virulent C. burnetii isolates during infection of primary human
      alveolar macrophages. A subset of PKA-specific substrates were differentially
      phosphorylated during C. burnetii infection, suggesting the pathogen uses PKA
      signaling to control distinct host cell responses. Collectively, the current
      results suggest a versatile role for PKA in C. burnetii infection and indicate
      virulent organisms usurp host kinase cascades for efficient intracellular growth.

PMID- 22473605
TI  - Ingested human insulin inhibits the mosquito NF-kappaB-dependent immune response
      to Plasmodium falciparum.
AB  - We showed previously that ingested human insulin activates the insulin/IGF-1
      signaling pathway in Anopheles stephensi and increases the susceptibility of
      these mosquitoes to Plasmodium falciparum. In other organisms, insulin can alter
      immune responsiveness through regulation of NF-kappaB transcription factors,
      critical elements for innate immunity that are also central to mosquito immunity.
      We show here that insulin signaling decreased expression of NF-kappaB-regulated
      immune genes in mosquito cells stimulated with either bacterial or malarial
      soluble products. Further, human insulin suppressed mosquito immunity through
      sustained phosphatidylinositol 3-kinase activation, since inhibition of this
      pathway led to decreased parasite development in the mosquito. Together, these
      data demonstrate that activation of the insulin/IGF-1 signaling pathway by
      ingested human insulin can alter NF-kappaB-dependent immunity, and ultimately the
      susceptibility, of mosquitoes to P. falciparum.

PMID- 22473606
TI  - Neutralizing antibodies elicited by a novel detoxified pneumolysin derivative,
      PlyD1, provide protection against both pneumococcal infection and lung injury.
AB  - Streptococcus pneumoniae pneumolysin (PLY) is a virulence factor that causes
      toxic effects contributing to pneumococcal pneumonia. To date, deriving a PLY
      candidate vaccine with the appropriate detoxification and immune profile has been
      challenging. A pneumolysin protein that is appropriately detoxified and that
      retains its immunogenicity is a desirable vaccine candidate. In this study, we
      assessed the protective efficacy of our novel PlyD1 detoxified PLY variant and
      investigated its underlying mechanism of protection. Results have shown that
      PlyD1 immunization protected mice against lethal intranasal (i.n.) challenge with
      pneumococci and lung injury mediated by PLY challenge. Protection was associated
      with PlyD1-specific IgG titers and in vitro neutralization titers. Pretreatment
      of PLY with PlyD1-specific rat polyclonal antiserum prior to i.n. delivery of
      toxin reduced PLY-mediated lung lesions, interleukin-6 (IL-6) production, and
      neutrophil infiltration into lungs, indicating that protection from lung lesions
      induced by PLY is antibody mediated. Preincubation of PLY with a neutralizing
      monoclonal PLY antibody also specifically reduced the cytotoxic effects of PLY
      after i.n. inoculation in comparison to nonneutralizing monoclonal antibodies.
      These results indicate that the induction of neutralizing antibodies against PLY
      can contribute to protection against bacterial pneumonia by preventing the
      development of PLY-induced lung lesions and inflammation. Our detoxified PlyD1
      antigen elicits such PLY neutralizing antibodies, thus serving as a candidate
      vaccine antigen for the prevention of pneumococcal pneumonia.

PMID- 22473607
TI  - Association of a protective monoclonal IgA with the O antigen of Salmonella
      enterica serovar Typhimurium impacts type 3 secretion and outer membrane
      integrity.
AB  - Invasion of intestinal epithelial cells by Salmonella enterica serovar
      Typhimurium is an energetically demanding process, involving the transfer of
      effector proteins from invading bacteria into host cells via a specialized
      organelle known as the Salmonella pathogenicity island 1 (SPI-1) type 3 secretion
      system (T3SS). By a mechanism that remains poorly understood, entry of S.
      Typhimurium into epithelial cells is inhibited by Sal4, a monoclonal, polymeric
      IgA antibody that binds an immunodominant epitope within the O-antigen (O-Ag)
      component of lipopolysaccharide. In this study, we investigated how the binding
      of Sal4 to the surface of S. Typhimurium influences T3SS activity, bacterial
      energetics, and outer membrane integrity. We found that Sal4 treatment impaired
      T3SS-mediated translocon formation and attenuated the delivery of tagged effector
      proteins into epithelial cells. Sal4 treatment coincided with a partial reduction
      in membrane energetics and intracellular ATP levels, possibly explaining the
      impairment in T3SS activity. Sal4's effects on bacterial secretion and energetics
      occurred concurrently with an increase in O-Ag levels in culture supernatants,
      alterations in outer membrane permeability, and changes in surface
      ultrastructure, as revealed by transmission electron microscopy and cryo-electron
      microscopy. We propose that Sal4, by virtue of its ability to bind and cross-link
      the O-Ag, induces a form of outer membrane stress that compromises the integrity
      of the S. Typhimurium cell envelope and temporarily renders the bacterium
      avirulent.

PMID- 22473608
TI  - Entamoeba histolytica cell surface calreticulin binds human c1q and functions in
      amebic phagocytosis of host cells.
AB  - Phagocytosis of host cells is characteristic of tissue invasion by the intestinal
      ameba Entamoeba histolytica, which causes amebic dysentery and liver abscesses.
      Entamoeba histolytica induces host cell apoptosis and uses ligands, including
      C1q, on apoptotic cells to engulf them. Two mass spectrometry analyses identified
      calreticulin in amebic phagosome preparations, and, in addition to its function
      as an endoplasmic reticulum chaperone, calreticulin is believed to be the
      macrophage receptor for C1q. The purpose of this study was to determine if
      calreticulin functions as an E. histolytica C1q receptor during phagocytosis of
      host cells. Calreticulin was localized to the surface of E. histolytica during
      interaction with both Jurkat lymphocytes and erythrocytes and was present in over
      75% of phagocytic cups during amebic erythrophagocytosis. Presence of
      calreticulin on the cell surface was further demonstrated using a method that
      selectively biotinylated cell surface proteins and by flow cytometry using
      trophozoites overexpressing epitope-tagged calreticulin. Regulated overexpression
      of calreticulin increased E. histolytica's ability to phagocytose apoptotic
      lymphocytes and calcium ionophore-treated erythrocytes but had no effect on
      amebic adherence to or destruction of cell monolayers or surface expression of
      the GalNAc lectin and serine-rich E. histolytica protein (SREHP) receptors.
      Finally, E. histolytica calreticulin bound specifically to apoptotic lymphocytes
      and to human C1q. Collectively, these data implicate cell surface calreticulin as
      a receptor for C1q during E. histolytica phagocytosis of host cells.

PMID- 22473609
TI  - Burkholderia pseudomallei triggers altered inflammatory profiles in a whole-blood
      model of type 2 diabetes-melioidosis comorbidity.
AB  - Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia
      pseudomallei. Type 2 diabetes (T2D) is the most common comorbidity associated
      with melioidosis. B. pseudomallei isolates from melioidosis patients with T2D are
      less virulent in animal models than those from patients with melioidosis and no
      identifiable risk factors. We developed an ex vivo whole-blood assay as a tool
      for comparison of early inflammatory profiles generated by T2D and nondiabetic
      (ND) individuals in response to a B. pseudomallei strain of low virulence.
      Peripheral blood from individuals with T2D, with either poorly controlled
      glycemia (PC-T2D [n = 6]) or well-controlled glycemia (WC-T2D [n = 8]), and
      healthy ND (n = 13) individuals was stimulated with B. pseudomallei. Oxidative
      burst, myeloperoxidase (MPO) release, expression of pathogen recognition
      receptors (TLR2, TLR4, and CD14), and activation markers (CD11b and HLA-DR) were
      measured on polymorphonuclear (PMN) leukocytes and monocytes. Concentrations of
      plasma inflammatory cytokine (interleukin-6 [IL-6], IL-12p70, tumor necrosis
      factor alpha [TNF-alpha], monocyte chemoattractant protein 1 [MCP-1], IL-8, IL
      1beta, and IL-10) were also determined. Following stimulation, oxidative burst
      and MPO levels were significantly elevated in blood from PC-T2D subjects compared
      to controls. Differences were also observed in expression of Toll-like receptor 2
      (TLR2), CD14, and CD11b on phagocytes from T2D and ND individuals. Levels of IL
      12p70, MCP-1, and IL-8 were significantly elevated in blood from PC-T2D subjects
      compared to ND individuals. Notably, differential inflammatory responses of PC
      T2D, WC-T2D, and ND individuals to B. pseudomallei occur independently of
      bacterial load and confirm the efficacy of this model of T2D-melioidosis
      comorbidity as a tool for investigation of dysregulated PMN and monocyte
      responses to B. pseudomallei underlying susceptibility of T2D individuals to
      melioidosis.

PMID- 22473611
TI  - Device engineering for highly efficient top-illuminated organic solar cells with
      microcavity structures.
AB  - Small-molecule organic solar cells with microcavity structures utilizing very
      thin solar-absorbing active layers are simulated and fabricated. By carefully
      fine-tuning the in-cell spacer layer and out-of-cell capping layer, highly
      efficient top-illuminated indium tin oxide-free solar cells are created on glass
      and flexible polyethylene terephthalate substrates with efficiencies of up to
      5.5% and 5%, respectively.

PMID- 22473610
TI  - Reactive oxygen species-triggered trophoblast apoptosis is initiated by
      endoplasmic reticulum stress via activation of caspase-12, CHOP, and the JNK
      pathway in Toxoplasma gondii infection in mice.
AB  - Toxoplasma gondii infection in pregnant women may result in abortion or in fetal
      teratogenesis; however, the underlying mechanisms are still unclear. In this
      paper, based on a murine model, we showed that maternal infection with RH strain
      T. gondii tachyzoites induced elevated production of reactive oxygen species
      (ROS), local oxidative stress, and subsequent apoptosis of placental
      trophoblasts. PCR array analysis of 84 oxidative stress-related genes
      demonstrated that 27 genes were upregulated at least 2-fold and that 9 genes were
      downregulated at least 2-fold in the T. gondii infection group compared with
      levels in the control group. The expression of NADPH oxidase 1 (Nox1) and
      glutathione peroxidase 6 (Gpx6) increased significantly, about 25-fold. The
      levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) increased
      significantly with T. gondii infection, and levels of glutathione (GSH) decreased
      rapidly. T. gondii infection increased the early expression of endoplasmic
      reticulum stress (ERS) markers, followed by cleavage of caspase-12, activation of
      ASK1/JNK, and increased apoptosis of trophoblasts, both in vivo and in vitro. The
      apoptosis of trophoblasts, the activation of caspase-12 and the ASK1/JNK pathway,
      and the production of peroxides were dramatically inhibited by pretreatment with
      N-acetylcysteine (NAC). The upregulation of Nox1 was contact dependent and
      preceded the increase in levels of ERS markers and the activation of the
      proapoptosis cascade. Thus, we concluded that apoptosis in placental trophoblasts
      was initiated predominantly by ROS-mediated ERS via activation of caspase-12,
      CHOP, and the JNK pathway in acute T. gondii infection. Elevated ROS production
      is the central event in T. gondii-induced apoptosis of placental trophoblasts.

PMID- 22473613
TI  - Phosphorous-functionalized bis(acyl)phosphane oxides for surface modification.

PMID- 22473614
TI  - MLR-1023 is a potent and selective allosteric activator of Lyn kinase in vitro
      that improves glucose tolerance in vivo.
AB  - 2(1H)-pyrimidinone,5-(3-methylphenoxy) (MLR-1023) is a candidate for the
      treatment of type 2 diabetes. The current studies were aimed at determining the
      mechanism by which MLR-1023 mediates glycemic control. In these studies, we
      showed that MLR-1023 reduced blood glucose levels without increasing insulin
      secretion in vivo. We have further determined that MLR-1023 did not activate
      peroxisome proliferator-activated alpha, delta, and gamma receptors or glucagon
      like peptide-1 receptors or inhibit dipeptidyl peptidase-4 or alpha-glucosidase
      enzyme activity. However, in an in vitro broad kinase screen MLR-1023 activated
      the nonreceptor-linked Src-related tyrosine kinase Lyn. MLR-1023 increased the
      V(max) of Lyn with an EC(50) of 63 nM. This Lyn kinase activation was ATP binding
      site independent, indicating that MLR-1023 regulated the kinase through an
      allosteric mechanism. We have established a link between Lyn activation and blood
      glucose lowering with studies showing that the glucose-lowering effects of MLR
      1023 were abolished in Lyn knockout mice, consistent with existing literature
      linking Lyn kinase and the insulin-signaling pathway. In summary, these studies
      describe MLR-1023 as a unique blood glucose-lowering agent and show that MLR-1023
      mediated blood glucose lowering depends on Lyn kinase activity. These results,
      coupled with other results (J Pharmacol Exp Ther 342:23-32, 2012), suggest that
      MLR-1023 and Lyn kinase activation may be a new treatment modality for type 2
      diabetes.

PMID- 22473615
TI  - Positive allosteric modulators differentially affect full versus partial agonist
      activation of the glycine receptor.
AB  - Taurine acts as a partial agonist at the glycine receptor (GlyR) in some brain
      regions such as the hippocampus, striatum, and nucleus accumbens. Ethanol,
      volatile anesthetics, and inhaled drugs of abuse are all known positive
      allosteric modulators of GlyRs, but their effects on taurine-activated GlyRs
      remain poorly understood, especially their effects on the high concentrations of
      taurine likely to be found after synaptic release. Two-electrode voltage-clamp
      electrophysiology in Xenopus laevis oocytes was used to compare the enhancing
      effects of ethanol, anesthetics, and inhalants on human homomeric alpha1-GlyR
      activated by saturating concentrations of glycine versus taurine. Allosteric
      modulators had negligible effects on glycine-activated GlyR while potentiating
      taurine-activated currents. In addition, inhaled anesthetics markedly enhanced
      desensitization rates of taurine- but not glycine-activated receptors. Our
      findings suggest that ethanol, volatile anesthetics, and inhalants differentially
      affect the time courses of synaptic events at GlyR, depending on whether the
      receptor is activated by a full or partial agonist.

PMID- 22473618
TI  - Determination of the static zero-field splitting of Gd3+ complexes in solution
      from the shifts of the central magnetic fields of their EPR spectra.
AB  - In principle, the Redfield theory of EPR spectra applies only to fast-rotating
      complexes with rather small static zero-field splitting (ZFS) terms. However, at
      sufficiently high frequencies, typically of 35 GHz and above, it predicts values
      of the central magnetic fields which are surprisingly accurate well beyond its
      expected applicability range. This remarkable feature is demonstrated by showing
      that the Redfield EPR spectrum crosses its baseline at the same point as its
      "exact" simulated counterpart. It is shown that the shift of the central magnetic
      field with respect to its limiting value in the absence of ZFS terms is often
      simply proportional to the square of the magnitude of the static ZFS term divided
      by the spectrometer frequency. This property is used to determine the magnitude
      of the static ZFS term independently of its fluctuation dynamics and of the
      presence of the transient ZFS term.

PMID- 22473616
TI  - Temporal integration of auditory and vestibular stimuli.
AB  - OBJECTIVES/HYPOTHESIS: Integration of balance-related cues from the vestibular
      and other sensory systems requires that they be perceived simultaneously despite
      arriving asynchronously at the central nervous system. Failure to perform
      temporal integration of multiple sensory signals represents a novel mechanism to
      explain symptoms in patients with imbalance. This study tested the ability of
      normal observers to compensate for sensory asynchronies between vestibular and
      auditory inputs. STUDY DESIGN: Double-blinded experimental design. METHODS: We
      performed whole-body rotations about the earth-vertical axis following a raised
      cosine trajectory at 0.5 and 1.0 Hz to several peak velocities up to a maximum of
      180 degrees /s in five normal subjects. Headphones were used to present a diotic
      auditory stimulus at various times relative to the onset of the rotation.
      Subjects were required to indicate which cue occurred first. RESULTS: The
      vestibular stimulus needed to be presented 61 milliseconds (at a stimulus
      frequency of 0.5 Hz) and 19 milliseconds (at 1.0 Hz) before the auditory
      stimulus. Stimuli presented within a window of 300 milliseconds (at 0.5 Hz) to
      200 milliseconds (at 1.0 Hz) were judged to be simultaneous. CONCLUSIONS: The
      central nervous system must accommodate for delays in perception of vestibular
      and other sensory cues. Inaccurate temporal integration of these inputs
      represents a novel explanation for symptoms of imbalance.

PMID- 22473620
TI  - On consideration of radiated power in RF field simulations for MRI.
AB  - In numerical analyses of radiofrequency (RF) fields for MRI, RF power is often
      permitted to radiate out of the problem region. In reality, RF power will be
      confined by the magnet bore and RF screen enclosing the magnet room. We present
      numerical calculations at different frequencies for various surface and volume
      coils, with samples from simple spheres to the human body in environments from
      free space to a shielded RF room. Results for calculations within a limited
      problem region show radiated power increases with frequency. When the magnet room
      RF screen is included, nearly all the power is dissipated in the human subject.
      For limited problem regions, inclusion of a term for radiation loss results in an
      underestimation of transmit efficiency compared to results including the complete
      bore and RF screen. If the term for radiated power is not included, calculated
      coil efficiencies are slightly overestimated compared to the complete case.

PMID- 22473619
TI  - Antiphospholipid syndrome: laboratory testing and diagnostic strategies.
AB  - The antiphospholipid syndrome (APS) is diagnosed in patients with recurrent
      thromboembolic events and/or pregnancy loss in the presence of persistent
      laboratory evidence for antiphospholipid antibodies. Diagnostic tests for the
      detection of antiphospholipid antibodies include laboratory assays that detect
      anticardiolipin antibodies, lupus anticoagulants, and anti-beta(2)-glycoprotein I
      antibodies. These assays have their origins beginning >60 years ago, with the
      identification of the biologic false positive test for syphilis, the observation
      of "circulating anticoagulants" in certain patients with systemic lupus
      erythematosus, the identification of cardiolipin as a key component in the
      serologic test for syphilis, and the recognition and characterization of a
      "cofactor" for antibody binding to phospholipids. Although these assays have been
      used clinically for many years, there are still problems with the accurate
      diagnosis of patients with this syndrome. For example, lupus anticoagulant
      testing can be difficult to interpret in patients receiving anticoagulant
      therapy, but most patients with a thromboembolic event will already be
      anticoagulated before the decision to perform the tests has been made. In
      addition to understanding limitations of the assays, clinicians also need to be
      aware of which patients should be tested and not obtain testing on patients
      unlikely to have APS. New tests and diagnostic strategies are in various stages
      of development and should help improve our ability to accurately diagnose this
      important clinical disorder.

PMID- 22473622
TI  - Childhood predictors of antipsychotic use among young people in Finland.
AB  - OBJECTIVE: Information on who uses antipsychotic medication is limited to cross
      sectional data. The objective of this study was to study the patterns of
      psychopathology at age 8 years and antipsychotic use between the ages of 12 and
      25 years. METHODS: A total of 5525 subjects from the Finnish Nationwide 1981
      birth cohort were linked to the National Prescription Register and the Hospital
      Discharge Register between 1994 and 2005. Information about parent-reported and
      teacher-reported conduct, hyperkinetic and emotional symptoms, and self-reported
      depressive symptoms was gathered at age 8 years. Information about antipsychotic
      use and about psychiatric disorders treated in hospitals between the ages of 12
      and 25 years was register based. Diagnostic classes of hospital treatment
      included non-affective psychoses, affective disorders, and other psychiatric
      disorders. RESULTS: The cumulative incidence of antipsychotic use by age 25 years
      was 2.8% among men (n = 69) and 2.1% among women (n = 55). In both sexes, living
      with other than two biological parents at age 8 years was associated with
      antipsychotic use, and three fourths of antipsychotic users had been treated for
      psychiatric disorders in a hospital. Among men, the most common hospital
      diagnosis was non-affective psychoses (44% of all antipsychotic users), and
      antipsychotic use was associated with childhood conduct problems. Among women,
      the most common hospital diagnosis was affective disorders (38% of all
      antipsychotic users), and antipsychotic use was associated with emotional
      problems and self-reported depressive symptoms in childhood. CONCLUSIONS:
      Antipsychotic use in adolescence and young adulthood is different among men
      versus women both with regard to hospital diagnoses and childhood psychiatric
      problems.

PMID- 22473623
TI  - The chemokine receptor CXCR4 as a novel independent prognostic marker for node
      positive breast cancer patients.
AB  - BACKGROUND: Node-positive breast cancer patients are a high-risk group. However,
      not all such patients will succumb to the disease. The molecular basis for this
      biologic heterogeneity is poorly understood. The chemokine receptor CXCR4 is a
      marker of metastatic disease. Its prognostic role in node-positive patients is
      unknown. We postulate that high CXCR4 overexpression in node-positive breast
      cancer specimens predicts a poor outcome. METHODS: 185 node-positive breast
      cancer patients were evaluated. All had standardized treatment and surveillance
      protocols. CXCR4 levels were detected with Western blots. Results were quantified
      against 1 ug of HeLa cells. CXCR4 expression was defined as high (>= 7.5-fold) or
      low (<7.5-fold). Primary endpoints were cancer recurrence and death. Statistical
      analyses were Kaplan-Meier curves, log-rank test, and Cox proportional hazard
      model, with a P-value of <= 0.05 as significant. RESULTS: The mean follow-up time
      was 54 months; 148 patients (80%) had low CXCR4 and 37 patients (20%) had high
      CXCR4 level. The 5-year overall survival (OS) for the low and high CXCR4 group
      was 69% and 57%, respectively (P=0.02). The 5-year disease-free survival (DFS)
      for the low and high CXCR4 group was 62% and 53%, respectively (P=0.08). On
      multivariate analysis, T stage (P=0.001) and grade (P=0.04) were independent
      predictors of DFS, while T stage (P=0.005), grade (P=0.024), and CXCR4 level
      (P=0.01) were independent predictors of OS. CONCLUSION: High CXCR4 level in
      cancer specimens independently predicts a poor outcome for patients with node
      positive breast cancer.

PMID- 22473624
TI  - Target-cell-specific delivery, imaging, and detection of intracellular microRNA
      with a multifunctional SnO2 nanoprobe.

PMID- 22473625
TI  - Prediction of clinical non-response to methotrexate treatment in juvenile
      idiopathic arthritis.
AB  - OBJECTIVES: Methotrexate (MTX) is a cheap and efficacious drug in juvenile
      idiopathic arthritis (JIA) treatment. If JIA patients are unresponsive to MTX,
      early and effective combination treatment with biologicals is required to prevent
      joint damage. The authors developed a prediction model to identify JIA patients
      not responding to MTX. METHODS: In a cohort of 183 JIA patients, clinical
      variables and single nucleotide polymorphisms (SNPs) in genes involved in the
      mechanism of action of MTX were determined at the start of MTX treatment. These
      variables were used to construct a prediction model for non-response to MTX
      treatment during the first year of treatment. Non-response to MTX was defined
      according the American College of Rheumatology paediatric 70 criteria. The
      prediction model was validated in a cohort of 104 JIA patients. RESULTS: The
      prediction model included: erythrocyte sedimentation rate and SNPs in genes
      coding for methionine synthase reductase, multidrug resistance 1 (MDR-1/ABCB1),
      multidrug resistance protein 1 (MRP-1/ABCC1) and proton-coupled folate
      transporter (PCFT). The area under the receiver operating characteristics curve
      (AUC) was 0.72 (95% CI: 0.63 to 0.81). In the validation cohort, the AUC was 0.65
      (95% CI: 0.54 to 0.77). The prediction model was transformed into a total risk
      score (range 0-11). At a cut-off of >=3, sensitivity was 78%, specificity 49%,
      positive predictive value was 83% and negative predictive value 41%. CONCLUSIONS:
      The prediction model that we developed and validated combines clinical and
      genetic variables to identify JIA patients not responding to MTX treatment. This
      model could assist clinicians in making individualised treatment decisions.

PMID- 22473626
TI  - Simultaneous reconstruction of head and neck defects following tumor resection
      and trismus release with a single anterolateral thigh donor site utilizing a
      lateral approach to flap harvest.
AB  - BACKGROUND: An anterolateral thigh (ALT) flap has gradually become the workhorse
      flap of reconstructions at different anatomical locations because of its
      reliability and versatility. In this study, we introduced the concepts: one is
      the ALT flap harvest from a lateral approach and the other is the reconstruction
      of extensive head and neck defects with a single ALT donor site. METHODS: A
      lateral approach ALT flap was harvested in 13 patients who had buccal cancer
      and/or tumors of the lower lip combined with buccal trismus. Three types of ALT
      flaps (type I: two skin paddles, one pedicle; type II: two skin paddles, two
      pedicles; type III: one skin paddle, one pedicle) were used in one-stage
      reconstructions of these extensive head and neck defects. RESULTS: In our series,
      there were four type I, five type II, and four type III flaps. All flaps survived
      and no major postoperative complication occurred. Four of the 13 donor sites were
      repaired with a split-thickness skin graft harvested from the contralateral
      thigh. The immediate interincisor distance increase was 21.4 and 16.5 mm at 1
      year follow-up. CONCLUSIONS: Different types of ALT flap from a single donor site
      can be designed by means of a lateral approach; and the satisfactory results of
      reconstruction for extensive head and neck defects following the tumor resection
      and trismus release can be achieved.

PMID- 22473627
TI  - Immobilization of large, aliovalent cations in the small-pore zeolite K-natrolite
      by means of pressure.
AB  - High-pressure ion exchange of small-pore zeolite K-natrolite allows
      immobilization of nominally non-exchangeable aliovalent cations such as trivalent
      europium. A sample exchanged at 3.0(1) GPa and 250  degrees C contains about 4.7
      Eu(III) ions per unit cell, which is equivalent to over 90 % of the K(+) cations
      being exchanged.

PMID- 22473628
TI  - Exploring the seasonality of birth defects in the New York State Congenital
      Malformations Registry.
AB  - BACKGROUND: Examining seasonal patterns of birth defects may help to identify
      environmental risk factors. Because the teratogenic window for most birth defects
      is during gestational weeks 3 to 8, investigating exposures closer to the timing
      of conception is important. However, studies are usually based on month of birth,
      which is not the biologically relevant exposure period and does not account for
      differences in gestational length. We aimed to determine whether the occurrence
      of birth defects varied by month of conception using the population-based New
      York State Congenital Malformations Registry (CMR). METHODS: We merged live birth
      certificates (n = 2,044,091) with CMR records for mothers residing in New York
      State, excluding New York City, for the years 1992 through 2006. We categorized
      birth defects according to the National Birth Defects Prevention Network
      guidelines and performed Cochran-Armitage trend, Hewitt-Rogerson, and Walter
      Elwood tests on month of conception and chi-square tests on season of conception.
      We graphed seasonal distributions and seasonality test results. We performed
      stratified analyses by maternal and infant characteristics. RESULTS: Of 42 groups
      examined in the 15-year period, 24 (57%) had at least one statistically
      significant test result, suggesting a trend or seasonal variation: Cochran
      Armitage (18), Hewitt-Rogerson (17), Walter-Elwood (4), and chi-square (5).
      Ventricular septal defect showed the most consistent results: Cochran-Armitage (p
      = 0.0006), Hewitt-Rogerson (December to May; p = 0.0130), Walter-Elwood (March
      14; p = 0.0027), and chi-square (winter; p = 0.0046). Congenital cataract,
      pulmonary valve atresia/stenosis, coarctation of aorta, biliary atresia, and
      renal agenesis or hypoplasia had at least three significant tests. DISCUSSION:
      These results may help to generate hypotheses about environmental factors that
      vary by season for further studies.

PMID- 22473629
TI  - Thrombotic thrombocytopenic purpura in a patient with hemoglobin E disease-the
      importance of timely examination of a blood film.

PMID- 22473631
TI  - Photoinduced symmetry-breaking charge separation.
AB  - Molecular systems where several apparently equivalent charge separation pathways
      exist upon photoexcitation are presented. They encompass MQ(n)  (n>=2)
      architectures, where M is a chromophore and Q an electron transfer quencher
      (either donor or acceptor), and M-M systems where M acts as both electron donor
      and acceptor. In all cases, charge separation involves symmetry breaking. The
      conditions for such process to be operative as well as the origin of the symmetry
      breaking are discussed.

PMID- 22473632
TI  - States with low non-fatal injury rates have high fatality rates and vice-versa.
AB  - BACKGROUND: State-level injury rates or fatality rates are sometimes used in
      studies of the impact of various safety programs or other state policies. How
      much does the metric used affect the view of relative occupational risks among
      U.S. states? This paper uses a measure of severe injuries (fatalities) and of
      less severe injuries (non-fatal injuries with days away from work, restricted
      work, or job transfer-DART) to examine that issue. METHODS: We looked at the
      correlation between the average DART injury rate (from the BLS Survey of
      Occupational Injuries and Illnesses) and an adjusted average fatality rate (from
      the BLS Census of Fatal Occupational Injuries) in the construction sector for
      states for 2003-2005 and for 2006-2008. The RAND Human Subjects Protection
      Committee determined that this study was exempt from review. RESULTS: The
      correlations between the fatal and non-fatal injury rates were between -0.30 and 
      0.70 for all construction and for the subsector of special trade contractors. The
      negative correlation was much smaller between the rate of fatal falls from
      heights and the rate of non-fatal falls from heights. Adjusting for differences
      in the industry composition of the construction sector across states had minor
      effects on these results. CONCLUSION: Although some have suggested that fatal and
      non-fatal injury rates should not necessarily be positively correlated, no one
      has suggested that the correlation is negative, which is what we find. We know
      that reported non-fatal rates are influenced by workers' compensation benefits
      and other factors. Fatality rates appear to be a more valid measure of risk.
      Efforts to explain the variations that we find should be undertaken.

PMID- 22473633
TI  - Naphthoquinone components from Alkanna tinctoria (L.) Tausch show significant
      antiproliferative effects on human colorectal cancer cells.
AB  - Our research to seek active compounds against human colorectal cancer from the
      root of Alkanna tinctoria (L.) Tausch led to the isolation of two
      naphthoquinones, alkannin (1) and angelylalkannin (2). The antiproliferative
      effects of the two compounds on human colon cancer cells HCT-116 and SW-480 were
      determined by the 3,4-(5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium salt (MTS) method. Cell cycle profile and cell
      apoptosis were determined using flow cytometry. Both of the two compounds showed
      significant inhibitory effects on the cancer cells. For alkannin (1) and
      angelylalkannin (2), the median inhibitory concentration (IC50) values were 2.38
      and 4.76 uM for HCT-116 cells, while for SW-480 cells they were 4.53 and 7.03 uM,
      respectively. The potential antiproliferative mechanisms were also explored. At
      concentrations between 1-10 uM, both compounds arrested the cell cycle at the G1
      phase and induced cell apoptosis.

PMID- 22473634
TI  - Dynamic monitoring of carnitine and acetylcarnitine in the trimethylamine signal
      after exercise in human skeletal muscle by 7T 1H-MRS.
AB  - A trimethylamine (TMA) moiety is present in carnitine and acetylcarnitine, and
      both molecules play critical roles in muscle metabolism. At 7 T, the chemical
      shift dispersion was sufficient to routinely resolve the TMA signals from
      carnitine at 3.20 and from acetylcarnitine at 3.17 ppm in the (1)H-MRS (Magnetic
      Resonance Spectroscopy) of human soleus muscle with a temporal resolution of
      about 2 min. In healthy, sedentary adults, the concentration of acetylcarnitine
      increased nearly 10-fold, to 4.1 +/- 1.0 mmol/kg, in soleus muscle after 5 min of
      calf-raise exercise and recovered to a baseline concentration of 0.5 +/- 0.3
      mmol/kg. While the half-time for decay of acetylcarnitine was the same whether
      measured from the TMA signal (18.8 +/- 5.6 min) or measured from the methyl
      signal (19.4 +/- 6.1 min), the detection of acetylcarnitine by its TMA signal in
      soleus has the advantage of higher sensitivity and without overlapping from lipid
      signals. Although the activity of carnitine acetyltransferase is sufficient to
      allow equilibrium between carnitine and coenzyme-A pools, the exchange in TMA
      signal between carnitine and acetylcarnitine is slow in soleus following exercise
      on 7T (1)H-NMR time scale. The TMA signal provides a simple and direct measure of
      the relative amounts of carnitine and acetylcarnitine.

PMID- 22473635
TI  - Victims of technology.

PMID- 22473636
TI  - Congenital heart defect case ascertainment by the Alberta Congenital Anomalies
      Surveillance System.
AB  - BACKGROUND: Congenital heart defects (CHDs) are the most common type of
      congenital anomaly, with a wide range of reported birth prevalence estimates.
      This quality assurance study describes CHD case ascertainment by the Alberta
      Congenital Anomalies Surveillance System (ACASS). METHODS: ACASS data for CHD
      cases were compared with additional sources including the two Pediatric
      Cardiology clinics in Alberta, the Alberta Children's Hospital Department of
      Pathology, and hospital records. Cases included live births, stillbirths, and
      fetal deaths at less than 20 weeks' gestation born in Alberta, Canada, between
      1995 and 2002. The birth prevalence of cases and chi-square linear trend analyses
      were calculated for specific types of heart defects for the total study period.
      RESULTS: The ascertainment of CHD cases by ACASS was 45%. The total prevalence of
      CHD cases was 5.59 per 1000 total births (TBs; 95% confidence interval [CI], 5.32
      5.86) when ACASS was the only data source and increased to 12.42 per 1000 TBs
      (95% CI, 12.03-12.83) when all data sources were used. Although the total
      prevalence of CHD cases remained stable during 1995 to 2002, the prevalence of
      atrial septal defect (ASD) and cases with an ASD and ventricular septal defect
      (VSD) significantly increased. The prevalence of left ventricular outflow tract
      obstruction cases significantly decreased during the study period. CONCLUSIONS:
      Pediatric cardiology clinics are worth including as additional ascertainment
      sources to contribute to more accurate prevalence estimates. The significant
      increases of ASD and cases with both an ASD and VSD may reflect differences in
      diagnostic and ascertainment practices.

PMID- 22473639
TI  - A highly active protonated tetranuclear peroxotungstate for oxidation with
      hydrogen peroxide.

PMID- 22473640
TI  - Dynamic cylindrical free-form deformation for interactive simulation of tool
      tissue interaction.
AB  - BACKGROUND: Dynamic lattice-based free-form deformation (FFD) allows efficient
      simulation of global deformation of complex geometric objects. However, directly
      imposing a number of position constraints due to contact with a tool is non
      trivial since it is an over-determined problem. METHOD: This paper extends the
      FFD to directly impose a number of position constraints for the objects to be
      embedded in (rounded) cylindrical lattice structures. The position constraints
      are applied by enabling each surface point to locally deform along the near
      normal direction to the surface. RESULT: The computational time of the local
      deformation is independent of the number of constrained points other than finite
      element method. As a real-time application, the proposed method is applied to
      colonoscopic polypectomy simulation running at over 60 Hz. CONCLUSION: The
      proposed method allows efficient simulation of the global and local deformations
      of complex geometric objects while achieving accurate tool-tissue interaction in
      a realistic and robust manner.

PMID- 22473642
TI  - Ionically tagged iron complex-catalyzed epoxidation of olefins in imidazolium
      based ionic liquids.
AB  - A new ionophilic ligand and a new ionically tagged imidazolium-based iron(III)
      complex were synthesized and applied in the air oxidation (also hydrogen
      peroxide) of alkenes in imidazolium-based ionic liquids. At least ten recycling
      reactions were performed. The epoxidized olefin was obtained in very good yields
      of 84-91 %. Some important mechanistic insights are also provided based on
      electrospray ionization quadrupole-time of flight mass spectrometry for the
      oxidation reaction. These results indicate that oxidations can take place by two
      different pathways, depending on the reaction condition: a radical or a concerted
      mechanism. These results contribute towards a better understanding of iron
      catalyzed oxidation mechanisms.

PMID- 22473644
TI  - Probing bioinspired transport of nanoparticles into polymersomes.

PMID- 22473645
TI  - Impact of the smoking ban on the volume of bar sales in Ireland: evidence from
      time series analysis.
AB  - This paper is the first to estimate the economic impact of a comprehensive
      smoking ban in all enclosed public places of work, on bars in Ireland. The demand
      in bars, represented by a monthly index of sales volume, is explained by relative
      prices in bars, prices of alcohol sold in off-licences and the aggregate retail
      sales (ARS) as a proxy for general economic activity and incomes. The smoking ban
      is included into the model as a step dummy and the modelling is done using ARIMAX
      strategy. The results show a reduction in the volume of sales in bars by -4.6%
      (p<0.01) following the ban.

PMID- 22473646
TI  - Comparative transcutaneous immunization with imiquimod-containing ointments and
      potential of in vitro methods to predict effects.
AB  - This work evaluates the transcutaneous in vitro and in vivo immunization efficacy
      of five commercially available 5% imiquimod containing formulations. The
      parameters included microscopic analysis, rheological properties, drug permeation
      across synthetic membranes of molecular weight cutoff 10 kDa and ablated murine
      skin with both 0.1 m HCl and a phthalate buffer pH 3.6 Ph.Eur./methanol 3/7 (v/v)
      as receiver solutions in a Franz-diffusion cell model. For in vivo formulation
      characterization, the cytotoxic T-cell activity and interferon-gamma production
      in C57BL/6 mice was determined ex vivo 24 h after transcutaneous administration.
      OVA(257-264) (SIINFEKL) from chicken albumin served as a target antigen.
      Microscopic images demonstrated differences with respect to the presence or
      absence of crystalline API. Rheological properties point to a roughly ten-fold
      difference between the products at low shear rates. With regard to drug
      permeation across synthetic membranes, only 'Nan Bo' demonstrated equality
      compared with AldaraTM, resulting in f1 and f2 values of 5.25 and 59.58,
      respectively. The drug permeation rates were maximum from AldaraTM across ablated
      murine skin. Furthermore, differentiation between the formulations containing
      crystalline and dissolved states of active imiquimod was possible using this
      model. The in vivo results yielded significant immunomodulating activities (p <
      0.05) of multisource formulations compared with the untreated control group,
      however, the significance of differences between the formulations was dependent
      on the parameter of interest. A correlation plot of skin permeation versus in
      vivo immunostimulating activity yielded a slope significantly different from zero
      only in the case of the murine skin setup (r between 0.421 and 0.669). Yet this
      correlation is deemed not satisfactory for formulation optimization.

PMID- 22473647
TI  - Antithrombin effect of polyphenol-rich extracts from black chokeberry and grape
      seeds.
AB  - Thrombin is a serine protease that cleaves the peptide bonds in proteins located
      on the carboxyl side of arginine. Thrombin plays a central role in thromboembolic
      diseases, which are the major cause of mortality. The aim of the study was to
      estimate the effects of plant extracts on proteolytic properties of thrombin.
      Thrombin was incubated with polyphenol-rich extracts from berries of Aronia
      melanocarpa or seeds of Vitis vinifera (0.5, 5, 50 ug/mL) and with polyphenols
      ((+)-catechin, (-)-epicatechin, gallic acid, chlorogenic acid, procyanidin B1,
      cyanidin, cyanidin 3-glucoside, quercetin). The in vitro experiments showed that
      both extracts in all used concentrations inhibited proteolytic activity of
      thrombin observed as inhibition of thrombin-induced fibrinogen polymerization,
      stabilized fibrin formation, and platelet aggregation. Moreover, thrombin
      amidolytic activity was inhibited by polyphenols belonging to the flavonoid
      class. Results presented in this study indicate that polyphenol-rich extracts
      from berries of A. melanocarpa and seeds of V. vinifera may become promising
      dietary supplements in the prevention of thrombotic states.

PMID- 22473648
TI  - The rotational advancement of medial plantar flap for coverage of foot defect: a
      case report.
AB  - This case describes the use of the medial plantar artery flap used to cover a
      lateral foot wound in a 19-year-old male with a history of spina bifida. The
      original operative plan was for coverage with a medial plantar flap based
      distally on retrograde flow through the lateral plantar artery; however, this had
      to be revised intraoperatively as his vascular anatomy was not adequate to
      support a flap of this type. Thus, advancement with rotation modification of the
      conventional medial plantar flap was performed with good results. At 2-month
      follow-up, the patient's flap had fully healed, he returned to full weight
      bearing status, and he had gross sensation in the sole of his foot. This case
      illustrates the use of the well-described medial plantar flap by rotating and
      advancing the flap for reconstruction of defects of the foot.

PMID- 22473649
TI  - Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors.
AB  - The new oral anticoagulants dabigatran, rivaroxaban and apixaban have advantages
      over warfarin which include no need for laboratory monitoring, less drug-drug
      interactions and less food-drug interactions. However, there is no established
      antidote for patients who are bleeding or require emergent surgery and there is a
      paucity of evidence to guide the clinical care during these situations. Members
      of thrombosis and anticoagulation groups participating in the Thrombosis and
      Hemostasis Summit of North America formulated expert opinion guidance for
      reversing the anticoagulant effect of the new oral anticoagulants and suggest:
      routine supportive care, activated charcoal if drug ingestion was within a couple
      of hours, and hemodialysis if feasible for dabigatran. Also, the pros and cons of
      the possible use of four factor prothrombin complex concentrate are discussed.

PMID- 22473650
TI  - Emotion and eating disorder symptoms in patients with anorexia nervosa: an
      experimental study.
AB  - OBJECTIVE: To evaluate the effect of negative emotion on self-reported eating
      disorder symptoms and objectively-measured eating behavior in patients with
      anorexia nervosa (AN). METHOD: Twenty-eight females with AN were randomized to a
      negative or neutral mood induction followed by a test meal. Participants
      completed assessments one week before the experimental session, before (pretest)
      and after (posttest) the mood induction, and after the test meal. RESULTS:
      Participants in the negative emotion condition had an increase in negative affect
      from pretest to posttest that was accompanied by significantly greater increases
      in self-reported eating disorder symptoms than were exhibited by participants in
      the neutral emotion condition, who had no increase in negative affect. There was
      no effect of emotion condition on eating behavior. DISCUSSION: Results suggest
      that negative emotions influence the expression of cognitive eating disorder
      symptoms in individuals with AN, which may have implications for the
      identification of treatment targets.

PMID- 22473651
TI  - Preconcentration of U(VI) ions on few-layered graphene oxide nanosheets from
      aqueous solutions.
AB  - Graphene oxide nanosheets have attracted multidisciplinary attention due to their
      unique physicochemical properties. Herein, few-layered graphene oxide nanosheets
      were synthesized from graphite using a modified Hummers method and were
      characterized by TEM, AFM, Raman spectroscopy, XPS, FTIR spectroscopy, TG-DTA and
      acid-base titrations. The prepared few-layered graphene oxide nanosheets were
      used as adsorbents for the preconcentration of U(VI) ions from large volumes of
      aqueous solutions as a function of pH, ionic strength and temperature. The
      sorption of U(VI) ions on the graphene oxide nanosheets was strongly dependent on
      pH and independent of the ionic strength, indicating that the sorption was mainly
      dominated by inner-sphere surface complexation rather than by outer-sphere
      surface complexation or ion exchange. The abundant oxygen-containing functional
      groups on the surfaces of the graphene oxide nanosheets played an important role
      in U(VI) sorption. The sorption of U(VI) on graphene oxide nanosheets increased
      with an increase in temperature and the thermodynamic parameters calculated from
      the temperature-dependent sorption isotherms suggested that the sorption of U(vi)
      on graphene oxide nanosheets was an endothermic and spontaneous process. The
      maximum sorption capacities (Q(max)) of U(VI) at pH 5.0 +/- 0.1 and T = 20 
      degrees C was 97.5 mg g(-1), which was much higher than any of the currently
      reported nanomaterials. The graphene oxide nanosheets may be suitable materials
      for the removal and preconcentration of U(VI) ions from large volumes of aqueous
      solutions, for example, U(VI) polluted wastewater, if they can be synthesized in
      a cost-effective manner on a large scale in the future.

PMID- 22473652
TI  - Effectiveness of a simple rapid human papillomavirus DNA test in rural Nigeria.
AB  - Success of the new human papillomavirus (HPV) DNA test for low-resource settings
      (careHPVTM test; QIAGEN Gaithersburg Inc., Gaithersburg, MD) requires good test
      performance when operated by personnel with limited laboratory experience. We
      evaluated the transferability, reliability, and accuracy of the careHPV test
      nested within a cervical screening project in a large Nigerian village. CareHPV
      testing was performed on screen-positive (n = 345) and screen-negative (n = 42)
      women attending colposcopy (68.3% of referred). Biopsies of abnormal-appearing
      areas were processed and read in the U.S. CareHPV specimens taken immediately
      before colposcopy were processed up to four times (in the field) by two secondary
      school graduates without laboratory experience, trained for this study.
      Specifically, QIAGEN Gaithersburg trained a laboratory-inexperienced U.S.
      researcher, who trained the first local technician who, in turn, trained the
      second. Residual specimens were sent to the U.S. for MY09/MY11 PCR testing for 13
      carcinogenic genotypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)
      plus HPV66 (included in careHPV). Intrarater agreement was 98.8% (kappa = 0.97)
      and 98.9% (kappa = 0.97) for Technicians 1 and 2, respectively, while inter-rater
      agreement was 96.3% (kappa = 0.90). Agreement with MY09/MY11 PCR (virologic
      reference standard) was 89.3% (kappa = 0.73) with 74.2% sensitivity and 95.7%
      specificity. The careHPV test detected 12 (80%) of 15 histologically confirmed
      cervical intraepithelial neoplasia Grade 2 (CIN2) or worse lesions, with an
      estimated 83.0% specificity to detect <CIN2. In a challenging low-resource
      setting with minimal intervention, the careHPV test performed adequately with
      high specificity but possibly lower sensitivity than HPV DNA tests currently used
      in controlled situations.

PMID- 22473653
TI  - Prenatal ablation of nicotinic receptor alpha7 cell lineages produces lumbosacral
      spina bifida the severity of which is modified by choline and nicotine exposure.
AB  - Lumbosacral spina bifida is a common debilitating birth defect whose multiple
      causes are poorly understood. Here, we provide the first genetic delineation of
      cholinergic nicotinic receptor alpha7 (Chrna7) expression and link the ablation
      of the Chrna7 cell lineage to this condition in the mouse. Using homologous
      recombination, an IRES-Cre bi-cistronic cassette was introduced into the 3'
      noncoding region of Chrna7 (Chrna7:Cre) for identifying cell lineages expressing
      this gene. This lineage first appears at embryonic day E9.0 in rhombomeres 3 and
      5 of the neural tube and extends to cell subsets in most tissues by E14.5.
      Ablation of the Chrna7:Cre cell lineage in embryos from crosses with
      conditionally expressed attenuated diphtheria toxin results in precise
      developmental defects including omphalocele (89%) and open spina bifida (SB;
      80%). We hypothesized that like humans, this defect would be modified by
      environmental compounds not only folic acid or choline but also nicotine.
      Prenatal chronic oral nicotine administration substantially worsened the defect
      to often include the rostral neural tube. In contrast, supplementation of the
      maternal diet with 2% choline decreased SB prevalence to 38% and dramatically
      reduced the defect severity. Folic acid supplementation only trended towards a
      reduced SB frequency. The omphalocele was unaffected by these interventions.
      These studies identify the Chrna7 cell lineage as participating in posterior
      neuropore closure and present a novel model of lower SB that can be substantially
      modified by the prenatal environment.

PMID- 22473656
TI  - Antiproliferative activity of polygonaceae species from the Carpathian Basin
      against human cancer cell lines.
AB  - Aqueous and organic extracts of 27 selected species from five genera (Fallopia,
      Oxyria, Persicaria, Polygonum and Rumex) of the family Polygonaceae occurring in
      the Carpathian Basin were screened in vitro for antiproliferative activity
      against HeLa (cervix epithelial adenocarcinoma), A431 (skin epidermoid carcinoma)
      and MCF7 (breast epithelial adenocarcinoma) cells, using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A total of 196 n
      hexane, chloroform, 50% methanol or water extracts of different plant parts were
      investigated. It was found that extracts of Polygonum hydropiper, Rumex acetosa,
      Rumex alpinus, Rumex aquaticus, Rumex scutatus and Rumex thyrsiflorus at 10 or 30
      ug/mL demonstrated substantial cell growth inhibitory activity (at least 50%
      inhibition of cell proliferation) against one or more cell lines. R. acetosa and
      R. thyrsiflorus proved to be the most active and are considered worthy of
      activity-guided phytochemical investigations.

PMID- 22473654
TI  - Pitfalls of electromagnetic tracking in clinical routine using multiple or
      adjacent sensors.
AB  - BACKGROUND: While electromagnetic tracking (EMT) holds great promise, there are
      substantiated concerns about interference within the clinical environment. The
      purpose of this study was to address accuracy and isolate pitfalls for using
      multiple or adjacent EMT sensors in clinical routine. METHODS: A phantom
      simulating an EMT-guided puncture of the kidney was used to analyse the effects
      of multiple sensors in the direct vicinity, common clinical environments and the
      influence of endo-urological instruments. RESULTS: No relevant interference due
      to the investigated instruments was discovered. However, there was a great
      decrease in accuracy in the vicinity of a C-arm's image intensifier, especially
      affecting the precision of two adjacent sensors. CONCLUSION: Endo-urological
      instruments can be safely used for multi-sensor EMT-guided procedures. When
      avoiding the immediate proximity of the surgical table and the image intensifier,
      there is a comfortable accuracy corridor. Thus, EMT-assistance is promising for a
      wide range of procedures if basic conditions are met.

PMID- 22473657
TI  - Cross-state disparities in US health care expenditures.
AB  - This study examines the degree of convergence in health care expenditures among
      the US states from 1980 to 2004. Our results suggest that the US states form two
      clubs with specific geographical characteristics that converge to different
      equilibria. We also extend our analysis to investigate the cross-state
      disparities in nine major components of health expenditures. Our findings provide
      evidence for full convergence for only two components, namely 'physician and
      other professional services' and 'home health care'. However, for the remaining
      components, we can still identify various convergence clubs.

PMID- 22473658
TI  - No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on
      gait function.
AB  - The aim of this study was to analyze gait function and muscular strength on donor
      site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine
      patients with a mean follow-up of 33 months (range, 7-59) and a mean resection
      length of the middle portion of the fibula of 18.0 cm (range, 14.0-23.0)
      underwent an instrumented three-dimensional gait analysis to evaluate gait
      function. Furthermore, CYBEX II extremity system was used for muscular strength
      measurements. Subjective muscle strength measurements were performed according to
      Kendall et al. and were classified according to the British Medical Research
      Council. Intraindividual comparison between the operated and the nonoperated leg
      revealed no significant differences for gait function parameters (cadence,
      velocity, and stride length, P > 1.00) and for muscular strength measurements for
      flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle:
      P= 0.21), respectively. In conclusion, intraindividual comparison of the operated
      and nonoperated sides after harvesting of the middle portion of the fibula for
      gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait
      function or muscular flexion and extension strength on donor site at a mean
      follow-up of 33 months.

PMID- 22473659
TI  - Effect of slaughter season and muscle type on the fatty acid composition,
      including conjugated linoleic acid isomers, and nutritional value of
      intramuscular fat in organic beef.
AB  - BACKGROUND: Consumer awareness regarding the intake of beef of organic origin is
      strongly associated with the beneficial outcomes to human health, the environment
      and animal welfare. In this paper the effects of slaughter season and muscle type
      on the fatty acid composition, conjugated linoleic acid (CLA) isomeric profile,
      total cholesterol, alpha-tocopherol and beta-carotene contents and nutritional
      quality of intramuscular fat in organic beef (n = 30) are reported for the first
      time. RESULTS: Organic beef showed a very low total lipid content, with seasonal
      changes in the levels of some fatty acids, CLA isomers, n-6/n-3 polyunsaturated
      fatty acid (PUFA) ratio, total cholesterol and beta-carotene. In addition,
      differences between longissimus lumborum (relatively red) and semitendinosus
      (relatively white) muscles were found for many fatty acids, specific CLA
      contents, many CLA isomers and both PUFA/saturated fatty acid (SFA) and n-6/n-3
      ratios. However, in spite of the seasonal and carcass variations, all organic
      meats analysed had values of beef similar to pasture-fed cattle. CONCLUSION: From
      a nutritional perspective, organic meat from both slaughter seasons seems to have
      high CLA contents, PUFA/SFA and n-6/n-3 indices within the recommended values for
      the human diet. The data indicate that intramuscular fat in organic meat has a
      high nutritional value throughout the year.

PMID- 22473660
TI  - Fast gated EPR imaging of the beating heart: spatiotemporally resolved 3D imaging
      of free-radical distribution during the cardiac cycle.
AB  - In vivo or ex vivo electron paramagnetic resonance imaging (EPRI) is a powerful
      technique for determining the spatial distribution of free radicals and other
      paramagnetic species in living organs and tissues. However, applications of EPRI
      have been limited by long projection acquisition times and the consequent fact
      that rapid gated EPRI was not possible. Hence in vivo EPRI typically provided
      only time-averaged information. In order to achieve direct gated EPRI, a fast EPR
      acquisition scheme was developed to decrease EPR projection acquisition time down
      to 10-20 ms, along with corresponding software and instrumentation to achieve
      fast gated EPRI of the isolated beating heart with submillimeter spatial
      resolution in as little as 2-3 min. Reconstructed images display temporal and
      spatial variations of the free-radical distribution, anatomical structure, and
      contractile function within the rat heart during the cardiac cycle.

PMID- 22473661
TI  - Organogold(III) supramolecular polymers for anticancer treatment.
AB  - Gold cures: the depicted gold(III) complex self-assembles into supramolecular
      polymers which form nanofibrillar networks that display sustained cytotoxicity
      and can also act as carriers for other cytotoxic agents.

PMID- 22473662
TI  - Drug discovery ... the third in the band!

PMID- 22473663
TI  - Autoimmune thrombotic microangiopathy: advances in pathogenesis, diagnosis, and
      management.
AB  - Thrombotic microangiopathy, or the syndrome of thrombocytopenia and hemolysis
      with schistocytes on blood smears, has been a subject of uncertainty and intense
      controversy. The pathogenesis of thrombotic microangiopathy was unknown and no
      classification of thrombotic thrombocytopenic purpura and hemolytic uremic
      syndrome was satisfactory. In recent years, a disintegrin and metalloproteinase
      with a thrombospondin type 1 motif, member 13 (ADAMTS-13) deficiency and
      defective complement regulation have been identified as the two major causes of
      noninfectious thrombotic microangiopathy. It is now possible to classify
      thrombotic microangiopathy pathogenetically rather than clinically, and a
      distinction between diseases and clinical syndromes is emerging. This
      pathogenesis-based disease classification requires new diagnostic approaches and
      provides a framework for rational therapeutic designs. This review discusses the
      new concepts in the pathogenesis, diagnosis, and management of thrombotic
      microangiopathy, with particular emphasis on the autoimmune causes of ADAMTS-13
      deficiency and defective complement regulation.

PMID- 22473664
TI  - Does a balloon atrial septostomy performed before arterial switch surgery
      increase adverse neurological outcomes?
AB  - This best evidence topic in congenital cardiac surgery was written according to a
      structured protocol. The question addressed was whether the use of balloon atrial
      septostomy (BAS) before the arterial switch surgery for transposition of the
      great arteries (TGA) improved the final outcome. Altogether more than 251 papers
      were found using the reported search, of which 12 represented the best evidence
      to answer the clinical question. The search was further limited to recent
      articles since the results have improved compared with previous years, due to
      newer equipment and techniques. This narrowed the search to five papers that have
      focused on this issue since 2006 when a study of 29 term neonates identified BAS
      as major risk factor for focal brain injury and reinvigorated the debate of
      adverse neurological outcome especially in the context of the fact that total
      correction by the arterial switch procedure is routine in neonates now.
      Subsequently, a prospective study of 64 newborn infants followed by another study
      of 26 neonates with TGA, have shown no association between BAS and brain injury.
      Similarly, in a study of more than 2000 cases of dTGA, no association has been
      found between BAS and increased risk of clinical stroke either in the neonatal
      period or in follow-up hospitalizations. On the other hand, another nationwide
      data analysis of 8681 patients with TGA, has shown increased risk of stroke in
      patients undergoing BAS but it could only show association and not establish
      causation of the complication. The authors, journal, date and country of
      publication, patient group studied, study type, relevant outcomes and results of
      these papers are tabulated.

PMID- 22473665
TI  - Can preoperative myocardial perfusion scintigraphy predict changes in left
      ventricular perfusion and function after coronary artery bypass graft surgery?
AB  - OBJECTIVES We wanted to evaluate whether preoperative myocardial perfusion
      scintigraphy (MPS) could predict changes in cardiac symptoms and postoperative
      myocardial perfusion and left ventricular function after coronary artery bypass
      grafting (CABG).  METHODS Ninety-two patients with stable angina pectoris (and at
      least one occluded coronary artery) underwent MPS before, and 6 months after,
      undergoing CABG. The result of the MPS was kept secret from the surgeons. 
      RESULTS Before CABG, 90% of the patients had angina. After CABG, 97% of the
      patients were without symptoms. Overall graft patency was 84%. Before CABG, one
      patient had normal perfusion; in the rest of them the defects were classified as
      follows: reversible (60%), partly reversible (27%) and irreversible (12%).
      Following CABG, 33% had normal perfusion; in the rest the defects were reversible
      in 29%, partly reversible in 12% and irreversible in 26%. Left ventricular
      ejection fraction (LVEF), which was normal before operation in 45%, improved in
      40% of all patients. The increase in LVEF was not related to the preoperative
      pattern of perfusion defects. Of 30 patients with normalized perfusion after
      CABG, 29 (97%) had reversible defects and one patient had partly reversible
      defects. Of 83 perfusion defects, which were normalized after CABG, 67 were
      reversible (81%) or partly reversible (12%). Seventy-five percent of all
      reversible coronary artery territories before CABG were normalized after
      operation.  CONCLUSIONS Our results indicate that reversible or partly reversible
      perfusion defects at a preoperative MPS have a high chance of normalized
      myocardial perfusion assessed by MPS 6 months after operation. Normal perfusion
      is obtained almost exclusively in territories with reversible ischaemia. Symptoms
      improved in nearly all patients and LVEF in a significant fraction of the
      patients, not related to preoperative MPS.

PMID- 22473666
TI  - The impact of major perioperative renal insult on long-term renal function and
      survival after cardiac surgery.
AB  - Temporary renal replacement therapy (RRT) facilitates recovery from a major
      perioperative renal injury and, although RRT can improve the hospital outcome, it
      is not known as to whether it mitigates long-term renal sequelae. Therefore, we
      investigated the risk of long-term dialysis after RRT post-cardiac surgery. We
      analysed prospectively the data collected for all hospital survivors who received
      RRT following cardiac surgery between March 1996 and July 2010, excluding those
      on dialysis preoperatively or with a functioning renal transplant. The follow-up
      data were obtained for all surviving patients. The mean age of the 82 patients
      was 68.6 +/- 9.9 years, and 60 (73%) were male. Severe pre-existing renal
      dysfunction with a serum creatinine level of >200 MUmol/l was present in 15 (18%)
      patients and diabetes in 31 (38%) patients. Operative procedures included redo
      surgery (n = 11, 13%) and thoracic aortic surgery (n = 9, 11%). During a 13.4
      year follow-up, there were 38 late deaths. Only three patients with severe
      preoperative renal dysfunction received dialysis. The Kaplan-Meier 5- and 7-year
      survival rates for this patient cohort were 54% and 38%, respectively. In
      conclusion, a major renal insult requiring temporary RRT after cardiac surgery
      does not increase the risk for renal dialysis in the long term for patients with
      normal renal function preoperatively.

PMID- 22473667
TI  - Three-dimensional computed tomography imaging of an implantable cardioverter
      defibrillator lead fragment in the left ventricle of a heart transplant followed
      by successful transarterial extraction with a snare catheter.
AB  - We report on a 51-year old heart transplant recipient in whom a pacing lead
      fragment of his old implantable cardioverter-defibrillator (ICD) had been
      detected in the left ventricle following successful heart transplantation. The
      patient was transplanted after 5 weeks on high urgent status. A postoperative
      routine chest X-ray and a subsequent cardiac three-dimensional (3D) computed
      tomography scan showed a metallic foreign body bending during systole below the
      posterior mitral valve leaflet within the left ventricle of the heart transplant.
      Transarterial extraction therapy was planned and the femoral artery was
      cannulated in the usual fashion. An 8F snare catheter was directed into the left
      ventricle under fluoroscopic guidance. Successful extraction revealed a 3-cm,
      uncoated ICD fragment (diameter = 0.025 in.). Following extraction of the
      fragment echocardiography showed mild mitral regurgitation but no further adverse
      events occurred. The patient was discharged 2 days later. Transarterial fragment
      extraction using a snare catheter is a feasible, minimally invasive procedure in
      this clinical scenario. Careful inspection of all explanted hardware is strongly
      recommended to ensure that no portion of an ICD lead is left behind.

PMID- 22473668
TI  - Dynamic asymmetric hemithioacetal transformation by lipase-catalyzed gamma
      lactonization: in situ tandem formation of 1,3-oxathiolan-5-one derivatives.
AB  - Dynamic hemithioacetal systems were efficiently generated in organic solvents and
      subsequently allowed to react with a range of lipases. This resulted in direct,
      dynamic asymmetric transformation of the systems, leading to optically active 1,3
      oxathiolan-5-one products. The tandem process identified lipase-catalyzed
      lactonization as a useful method for the resolution of optimal constituents with
      high chemo- and stereoselectivities.

PMID- 22473669
TI  - Circadian genes and breast cancer susceptibility in rotating shift workers.
AB  - Rotating night shift work is associated with increased risk of breast cancer,
      likely via circadian disruption. We hypothesized that circadian pathway genes
      influence breast cancer risk, particularly in rotating night shift workers. We
      selected 178 common variants across 15 genes pertinent to the circadian system.
      Using a mixed candidate- and tag-single nucleotide polymorphism approach, we
      tested for associations between these variants and breast cancer risk in 1,825
      women within the Nurses' Health Study II cohort and investigated potential
      interactions between genotype and rotating shift-work in a subset of 1,318 women.
      Multiple-testing-adjusted p-values were obtained by permutation (n = 10,000).
      None of the selected variants was significantly associated with breast cancer
      risk. However, when accounting for potential effect modification, rs23051560
      (Ala394Thr) in the largest circadian gene, Neuronal PAS domain protein 2 (NPAS2)
      was most strongly associated with breast cancer risk (nominal test for
      interaction p-value = 0.0005; 10,000-permutation-based main-effects p-value among
      women with < 24 months of shift-work = 0.003). The observed multiplicative
      association with breast cancer risk per minor allele (A) was 0.65 (95% CI = 0.51
      0.82) among women with < 24 months of shift-work and 1.19 (95% CI = 0.93-1.54)
      with >= 24 months of shift-work. Women homozygous for the minor allele (AA) with
      >= 24 months of shift-work had a 2.83-times higher breast cancer risk compared to
      homozygous AA women with < 24 months of shift-work (95% CI = 1.47-5.56). In
      summary, common variation in circadian genes plays at most a small role in breast
      cancer risk among women of European ancestry. The impact of NPAS2 Ala394Thr in
      the presence of rotating shift-work requires further investigation.

PMID- 22473671
TI  - Trends in in-hospital deaths among hospitalizations with pulmonary embolism.

PMID- 22473672
TI  - The diagnosis and treatment of pulmonary embolism: a metaphor for medicine in the
      evidence-based medicine era.
AB  - BACKGROUND: The history of pulmonary embolism (PE) provides a fascinating
      portrait of a well-established diagnosis and standard of care treatment moving
      into the age of evidence-based medicine. METHODS: We examined the history of PE
      and the practice of treating PE with anticoagulation. RESULTS: Pulmonary embolism
      is a diagnostic category whose definition and treatment have both changed in the
      past century. Initially, PE was recognizable only when massive, with the signs
      and symptoms of right heart failure. Anticoagulants were established as the
      cornerstone of PE management with a single randomized controlled trial of 35
      patients in 1960 and based on commonsense pathophysiologic reasoning. Since then,
      the diagnostic category of PE has been broadened, and the advent of computed
      tomography pulmonary angiography has yielded nearly a doubling of the incidence
      of the disease, without a concordant decrease in mortality. Although
      anticoagulation remains the cornerstone of management, open questions remain:
      what end points are altered by anticoagulation? What is the number needed to
      treat? CONCLUSIONS: Trials of newer anticoagulants and longer durations of
      anticoagulation have not yielded real improvements over heparin, inviting doubts
      regarding its efficacy. Thus, PE is the quintessential diagnosis of medicine not
      because it represents our greatest success, but because it captures all the
      complexity of medicine in the evidence-based era. It may serve as a metaphor for
      many other conditions in medicine, including coronary artery disease. New trials
      in the field continue to test trivialities, whereas fundamental questions are
      unanswered.

PMID- 22473673
TI  - [Surgical treatment and prognosis of rectovaginal fistulae according to their
      origin].
AB  - INTRODUCTION: The rectovaginal fistula is a rare entity with heterogenic
      causality. Its genesis seems to predict the extent of operative treatment and the
      prognostic outcome. The aim of this study was to present different surgical
      techniques in the treatment of rectovaginal fistulas and their results in
      correspondence to the genesis. MATERIAL AND METHODS: Between 1 / 2000 and 1 /
      2010, the data of patients with rectovaginal fistulas were collected. The
      retrospective analysis included biographic and anamnestic data as well as
      clinical parameters, general and specific complications and postoperative data.
      RESULTS: In a timespan of ten years 36 patients with rectovaginal fistulas were
      treated. The most common causes were inflammatory diseases (n = 21) and earlier
      surgical measures (n = 6). Moreover tumour-associated fistulas (n = 5) and
      fistulas with unknown genesis (n = 4) were seen. As surgical techniques anterior
      resection (n = 21), transrectal flap plasty (n = 7), subtotal colectomy (n = 3),
      pelvine exenteration (n = 2) and rectal exstirpation (n = 1) were used. The
      closure of the vaginal lesion was performed by single suture (n = 25), flap
      plasty (n = 6), transvaginal omental plasty (n = 2) and posterior vaginal plasty
      (n = 1). All patients were provided with an omental plasty to perform a safe
      division of the concerned regions. Patients with a low fistula ( < 6 cm) were
      treated with transperineal omental plasty. The median follow-up was 12 months (6 
      36). Within this timespan 6 patients suffered from major complications [ARDS,
      anastomosis insufficiency, postoperative bleeding, recurrence of fistula (n =
      3)]. Three patients died in the postoperative period (cerebellar infarct, septic
      complication associated with Crohn's disease, multiorgan failure in tumour
      recurrence). CONCLUSION: The genesis of rectovaginal fistulae is an important
      predictor for the size of resection which can range from simple excision to
      exenteration. For optimal therapy the surgical intervention needs to be
      integrated into an interdisciplinary therapy concept.

PMID- 22473674
TI  - Retracted: Notch activation is regulated by an interaction between hCLP46 and
      chaperone protein calnexin.

PMID- 22473676
TI  - Robot-assisted laparoscopic abdominoperineal resection for low rectal cancer.
AB  - BACKGROUND: This article reports on patients with low rectal cancer treated with
      robot-assisted laparoscopic abdominoperineal resection. METHODS: Robot-assisted
      laparoscopic abdominoperineal resection was performed on seven patients in the
      General Surgery Clinic of Umraniye Training and Research Hospital between 2010
      and 2011 by performing abdominal and perineal skin incisions using the same
      technique. Gender, age of the patients, intraoperative and postoperative
      complications, morbidity and mortality were evaluated. RESULTS: Five of the
      patients were male and two of them were female. Mean age was 59.2 years. All of
      the procedures were completed robotically. No intraoperative complication
      occurred, whereas urinary bladder dysfunction (n = 1) and chylous ascites (n =
      1), treated conservatively, developed in the postoperative period. On
      histopathological examination, surgical and circumferential margins were found to
      be negative in all specimens. Early recurrence was not found on postoperative
      follow-up. CONCLUSION: Robot-assisted laparoscopic surgery can be performed
      safely in narrow and deep anatomical areas, such as the pelvis.

PMID- 22473675
TI  - Implication of perturbed axoglial apparatus in early pediatric multiple
      sclerosis.
AB  - Cerebrospinal fluid samples collected from children during initial presentation
      of central nervous system inflammation, who may or may not subsequently be
      diagnosed as having multiple sclerosis (MS), were subjected to large-scale
      proteomics screening. Unexpectedly, major compact myelin membrane proteins
      typically implicated in MS were not detected. However, multiple molecules that
      localize to the node of Ranvier and the surrounding axoglial apparatus membrane
      were implicated, indicating perturbed axon-glial interactions in those children
      destined for diagnosis of MS.

PMID- 22473677
TI  - Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex
      vivo biomimicry.
AB  - Haematopoietic stem cells (HSCs) and haematopoietic progenitor cells (HPCs) grow
      in a specified niche in close association with the microenvironment, the so
      called 'haematopoietic niche'. Scaffolds have been introduced to overcome the
      liquid culture limitations, mimicking the presence of the extracellular matrix
      (ECM). In the present study the hyaluronic acid scaffold, already developed in
      the laboratory, has been used for the first time to maintain long-term cultures
      of CD34+ haematopoietic cells obtained from human cord blood. One parameter
      investigated was the impact on ex vivo survival of CD34+ cord blood cells (CBCs)
      on the hyaluronic acid surface, immobilized with peptides containing the RGD
      motif. This peptide was conjugated by coating the hyaluronan hydrogel and
      cultured in serum-free liquid phase complemented with stem cell factor (SCF), a
      commonly indispensable cytokine for haematopoiesis. Our work demonstrated that
      these hyaluronan hydrogels were superior to traditional liquid cultures by
      maintaining and expanding the HPCs without the need for additional cytokines, and
      a colonization of 280-fold increment in the hydrogel compared with liquid culture
      after 28 days of ex vivo expansion.

PMID- 22473678
TI  - Gold(I) styrylbenzene, distyrylbenzene, and distyrylnaphthalene complexes: high
      emission quantum yields at room temperature.
AB  - One gold(I)-substituted styrylbenzene, six digold(I) distyrylbenzenes, one
      tetragold distyrylbenzene, and four digold distyrylnaphthalene complexes were
      synthesized using base-promoted auration, alkynylation, triazolate formation, and
      Horner-Wadsworth-Emmons reactions. The gold(I) fragments are either sigma-bonded
      to the aromatic system, or they are attached through an alkynyl or triazolate
      spacer. Product formation was monitored using (31)P{(1)H} NMR spectroscopy.
      Systems in which gold(I) binds to the central benzene ring or the terminal phenyl
      rings were designed. All of these complexes have strong ultraviolet absorptions
      and emit blue light. The position of the gold(I) attachment influences the
      luminescence efficiency. Complexes with two gold(I) fragments attached to the
      ends of the conjugated system have fluorescence quantum yields up to 0.94, when
      using 7-diethylamino-4-methylcoumarin as the emission standard. Density
      functional theory calculations on three high-yielding emitters suggest that
      luminescence originates from the distyrylbenzene or -naphthalene bridge.

PMID- 22473679
TI  - Incorporation of prior knowledge in compressed sensing for faster acquisition of
      hyperpolarized gas images.
AB  - Adding prior knowledge to compressed sensing reconstruction can improve image
      reconstruction. In this work, two approaches are investigated to improve
      reconstruction of two-dimensional hyperpolarized (3)He lung ventilation images
      using prior knowledge. When compared against a standard compressed sensing
      reconstruction, the proposed methods allowed acquisition of images with higher
      under-sampling factors and reduction of the blurring effects that increase with
      higher reduction factors when fixed flip angles are used. These methods
      incorporate the prior knowledge of polarization decay of hyperpolarized (3)He and
      the mutual anatomical information from a registered (1)H image acquired in the
      same breath. Three times accelerated two-dimensional images reconstructed with
      compressed sensing and prior knowledge gave lower root-mean square error, than
      images reconstructed without introduction of any prior information. When
      introducing the polarization decay as prior knowledge, a significant improvement
      was achieved in the lung region, the root mean square value decreased by 45% and
      from the whole image by 36%. When introducing the mutual anatomical information
      as prior knowledge, the root mean square decreased by 21% over the lung region
      and by 15% over the whole image.

PMID- 22473680
TI  - High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a
      reappraisal of prognostic factors.
AB  - High-dose chemotherapy (HDCT) has a consolidated role in the treatment of
      patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical
      results of 97 HL patients who underwent HDCT for refractory (62 patients) or
      relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to
      2009. Treatment included high-dose carmustine, etoposide, cytarabine and
      melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients
      with subsequent peripheral hemopoietic stem cells transplant. Outcomes were
      evaluated in terms of progression-free survival (PFS) and overall survival (OS).
      In order to identify prognostic factors for outcome, a multivariate analysis for
      age, sex, disease status (refractory/relapsed), disease stage, B symptoms,
      presence of extranodal involvement, bulky disease, elevated lactate
      dehydrogenase, number of previous chemotherapy lines, remission status before
      transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG
      PET) status before and after transplant was done. A clinical response was
      achieved in 91% of patients, with complete remissions in 76/97 patients. With a
      median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64%
      and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy
      d-glucose positron emission tomography status before and after transplant were
      the most important prognostic factors for PFS and OS in univariate or
      multivariate analyses. HDCT is able to induce a high remission rate and a
      prolonged PFS in more than 50% of the patients with refractory and relapsed HL.

PMID- 22473681
TI  - The effect of betaine on in vitro fermentation of carbohydrate and protein
      combinations under osmotic stress in pigs.
AB  - BACKGROUND: There is evidence that dietary betaine might improve nutrient
      digestibilities in pigs due to its osmoprotective properties. This in vitro study
      was performed to assess the potential of supplemented betaine sources to affect
      fermentation characteristics of different carbohydrate and protein combinations,
      under conditions of osmotic stress. In vitro fermentation was performed by use of
      the modified Hohenheim gas test with pig faeces as microbial inoculum. RESULTS:
      At the end of in vitro fermentation under osmotic stress conditions, differences
      (P < 0.05) in gas production, ammonia concentration, and concentration of short
      chain fatty acids were observed for the different carbohydrates, while for the
      two proteins only differences (P < 0.05) in ammonia and short-chain fatty acid
      concentration were obtained. Supplementation of a native betaine source rather
      than addition of pure betaine increased propionic acid (P < 0.05) and butyric
      acid (P < 0.05) production. CONCLUSION: These results suggest that only
      supplementation of a native betaine source but not of pure betaine products
      affects microbial fermentation under osmotic stress. Furthermore, both the
      carbohydrate and protein source play an important role in modifying microbial
      activity under osmotic stress conditions. It can also be concluded that the
      modified Hohenheim gas test is suitable to scrutinise fermentation activity of
      different assay substrates under osmotic stress.

PMID- 22473682
TI  - Regulation of redox potential of a pterin derivative bound to a ruthenium(II)
      complex by intermolecular hydrogen bonding with nucleobases.

PMID- 22473683
TI  - Outcomes of flap salvage with medicinal leech therapy.
AB  - Medicinal leech therapy (MLT) to salvage venous congestion in native skin and
      local flaps is commonly practiced. However, the role of MLT in compromised
      regional and free flaps remains unclear. Leeches were used in 39 patients to
      treat venous congestion in native skin (n = 5), local flaps (n = 6), regional
      flaps (n = 14), and free flaps (n = 14). There were no total losses in patients
      with compromised native skin or local flaps. One patient who had received a
      radial forearm free flap expired before flap outcome could be assessed, and was
      excluded from analysis. Of the remaining 27 regional and free flaps, 33.3% were
      salvaged, 33.3% were partially salvaged, and 33.3% were lost. Means of 38.3 +/-
      34.0, 101.0 +/- 11.2, and 157.9 +/- 224.4 leeches and 1.7 +/- 3.6, 3.2 +/- 4.4,
      and 5.6 +/- 5.2 units of blood were required for the salvaged, partially
      salvaged, and lost groups, respectively. Twenty-two patients required blood
      transfusion (57.9%). No patients developed wound infection with Aeromonas
      hydrophilia. Two patients developed donor site hematomas, and four patients
      developed recipient site hematomas. MLT is efficacious in congested native skin
      and local flaps. Some regional and free flaps can be totally or partially
      salvaged. However, the morbidity of MLT must be weighed against the risks of flap
      loss.

PMID- 22473684
TI  - ["Fortschritte" opens new platform for english language submissions].

PMID- 22473685
TI  - [Acute neuropathy with tetraparesis and respiratory insufficiency in cases of
      acute intermittent porphyria].
AB  - Acute intermittent porphyria is a hereditary disorder resulting from a partial
      deficiency of the third enzyme in the haeme biosynthetic pathway. Symptoms are
      due to metabolic effects on the peripheral autonomic and sensomotoric, as well as
      the central nervous system. We report on the case of a life-threatening acute
      crisis with tetraplegia and respiratory insufficiency.

PMID- 22473686
TI  - [Treatment with psychopharmaca during pregnancy - part I: as little as possible
      but as much as necessary].

PMID- 22473687
TI  - Impact of hyponatremia and the syndrome of inappropriate antidiuresis on
      mortality in elderly patients with aspiration pneumonia.
AB  - BACKGROUND: Hyponatremia is associated with pneumonia, and aspiration pneumonia
      is common in the elderly, however, there has been no study of hyponatremia in
      this population. OBJECTIVE: To determine the impact of hyponatremia on mortality
      in elderly patients with aspiration pneumonia, while focusing on the comparison
      between those with and without the syndrome of inappropriate antidiuresis (SIAD).
      DESIGN: Retrospective review of existing database and medical records. SETTING: A
      community teaching hospital in Japan. PATIENTS: Two hundred and twenty-one
      elderly patients hospitalized with aspiration pneumonia. MEASUREMENTS:
      Multivariate logistical regression models were used to compare 30-day and in
      hospital mortality, in patients with hyponatremia of various severities and
      etiologies, with that in patients with normal serum sodium concentrations.
      RESULTS: Sixty-five (29%) of 221 patients had hyponatremia. Of these 62 (95%) had
      hypotonic hyponatremia, which were further assessed as having hypovolemic (39
      [63%]), hypervolemic (3 [5%]), and euvolemic (20 [32%]) hyponatremia. Of the 20
      euvolemic patients, 14 (70%) had SIAD. Both moderate and severe hypotonic
      hyponatremia were significantly associated with increased in-hospital mortality
      (odds ratio [OR] 6.05, 95% confidence interval [CI] 1.46-25.0, and OR 5.65, 95%
      CI 1.14-28.1, respectively). Hyponatremia due to SIAD was significantly
      associated with both increased 30-day mortality (OR 7.40, 95% CI 1.73-31.7) and
      increased in-hospital mortality (OR 22.3, 95% CI 4.26-117). In contrast,
      hypovolemic hyponatremia was not significantly associated with increased
      mortality. CONCLUSIONS: Hyponatremia due to SIAD was strongly associated with
      increased mortality in elderly patients with aspiration pneumonia, whereas
      hypovolemic hyponatremia was not associated with increased mortality.

PMID- 22473688
TI  - Peer effects in adolescent BMI: evidence from Spain.
AB  - This paper extends the recent literature on the influence of peers on adolescent
      weight on three new fronts. First, based on a survey of secondary school students
      in Spain in which peers are formed by nominated classmate friends, we find a more
      powerful positive and significant causal effect of friends' mean BMI on
      adolescent BMI than previous US-based research. These results are in line with
      international data, which show that peer group contact tends to vary across
      countries. Our findings cover a large set of controls, fixed effects, the testing
      of correlated unobservables, contextual influences and instrumental variables.
      Second, social interactions are identified through the property of intransitivity
      in network relationships. Finally, we report evidence of a strong, positive
      effect of peer pressure on several subgroups of adolescents in an attempt to
      study their vulnerability to social influences.

PMID- 22473689
TI  - Peroxisome morphology in pathology.
AB  - Peroxisomes are remarkably dynamic and versatile organelles that are essential
      for human health and development. They respond to physiological changes in the
      cellular environment by adapting their morphology, number, enzyme content and
      metabolic functions accordingly. With the discovery of the first key peroxisomal
      morphology proteins, the investigation of peroxisomal shape, distribution and
      dynamics has become an exciting new field in cell biology and biomedical sciences
      because of its relation to organelle functionality and its impact on
      developmental and physiological processes. In this review, we summarize recent
      findings on peroxisome biology, dynamics and the modulation of peroxisome
      morphology, especially in mammals. Furthermore, we discuss the roles of
      peroxisome dynamics and morphology in cell pathology and present recent examples
      for alterations in peroxisome morphology under disease conditions. Besides
      defects in the peroxisomal morphology machinery, we also address peroxisome
      biogenesis disorders, alterations of peroxisome number during carcinogenesis and
      liver cirrhosis, and morphological alterations of peroxisomes during viral
      infection.

PMID- 22473690
TI  - Clinical significance of Src expression and activity in human neoplasia.
AB  - Src, a 60 kDa non-receptor tyrosine kinase, is the product of normal c-src of the
      human genome and member of the Src protein tyrosine kinases family (SFK). As
      described by Martin and Rous, a genetic recombination between c-src and the RSV
      oncogene of Rous sarcoma virus results in a modified Src protein, with increased
      intrinsic activity and transforming potential in animal and human tissues.
      Several in vitro and in vivo studies supported this theory providing insight in
      the signalling pathways involved. Accumulating evidence from studies on clinical
      samples supported the role of Src in the process of carcinogenesis and disease
      progression in several human malignancies. Some studies have further reinforced
      the significance of the kinase in malignacy by correlating its expression and/or
      activity with important clinicopathological parameters, such as tumour stage,
      histopathological grade, proliferative capacity and most importantly patient's
      survival. This review is a comprehensive report of the published evidence on the
      expression and clinical significance of Src in human malignancy, which
      constitutes the background of the current studies and clinical trials on the use
      of Src inhibitors as novel potent antineoplastic strategy.

PMID- 22473691
TI  - Extracellular matrix, biotensegrity and tumor microenvironment. An update and
      overview.
AB  - The extracellular matrix (ECM) constitutes a three-dimensional network that
      surrounds all cells, organs and tissues in the body. It forms a biophysical
      filter for protection, nutrition and cell innervation, as well as the medium for
      facilitating immune response, angiogenesis, fibrosis and tissue regeneration. It
      is the mechanism by which mechanical forces are transmitted to the basement
      membrane which, through the integrins, supports the tensegrity system and
      activates the epigenetic mechanisms of the cell. A review and update on current
      knowledge on this topic reveals how disturbance of the ECM leads to a loss of
      efficient filtering, nutrition, elimination, and cell denervation functions, in
      addition to loss of regeneration capacity and disorders in mechanotransduction.
      Furthermore, such disturbance results in a loss of substrate, and with it the
      ability to provide a proper immune response against tumor, toxic and infectious
      agents. Reciprocal communication between ECM stromal and parenchymatous cells
      directs gene expression. The oncogenic capacity of the stroma derives from the
      associated cells as well as from the tumor cells, the angiogenic microenvironment
      and from an alteration in tensegrity; all of which are dependent on the ECM. It
      has been shown that the malignant phenotype is reversible by correction of the
      altered cues of the ECM.

PMID- 22473692
TI  - Ovarian cancer: insights into genetics and pathogeny.
AB  - Starting from the information on ovarian cancer provided by the mainstream
      publications, we construct a review focusing on the following issues: (i) the
      genetic profile, (ii) the role of the epithelial-mesenchymal transition in the
      acquirement of malignant features, (iii) the controversial hypothesis regarding
      the origin, and (iv) the involvement of the immune system in the tumoral
      microenvironment. Advances in the decipherment at the genetic level in the
      pathogenic mechanisms progressively lead to the idea of a genetic signature for
      the ovarian cancer. Moreover, the complementary approaches oriented towards the
      decryption of the intrinsic structure of the expressed molecules and, implicitly,
      the development of proteomics open new perspectives for an early diagnosis and an
      appropriate treatment. The research on the epithelial-mesenchymal transition
      (mainly those exploring the signaling pathways responsible for the switch between
      the loss of the epithelial characteristics and the gain of a mesenchymal cell
      phenotype, with results in the amplification of differentiation, motility and
      tumoral invasion) allow a deeper understanding of the complex pathogenic
      mechanism which governs ovarian carcinogenesis. The classic conception of ovarian
      cancer pathogeny, based on the role of the ovarian surface epithelium, is
      currently reconsidered, and a novel hypothesis is formulated, which supports
      direct involvement of the Fallopian tubes for the serous type. Although recent
      research suggests the implication of immune/inflammatory cells by specific
      mechanisms in ovarian cancer pathogenesis, there is yet reliable evidence
      concerning their modality of direct action and/or modulation of tumoral growth.
      Thus, ovarian carcinogenesis remains a research challenge, due to still numerous
      unknown factors involved in the malignant transformation sequences, originating
      from the genetic-molecular alterations and reflected by cellular and tissue
      expression patterns.

PMID- 22473693
TI  - The lymphangiogenesis inhibitor esVEGFR-2 in human embryos: expression in
      sympatho-adrenal tissues and differentiation-induced up-regulation in
      neuroblastoma.
AB  - Tumour-induced hem- and lymph-angiogenesis are frequently associated with tumour
      progression. Vascular endothelial growth factor-C (VEGF-C) is a potent inducer of
      lymphangiogenesis, while the endogenous soluble splice-variant of VEGF receptor
      2, esVEGFR-2, acts as a natural inhibitor. Previously we have shown down
      regulation of esVEGFR-2 mRNA in progressed stages of neuro-blastoma (NB), a
      tumour derived from sympatho-adrenal precursor cells. Here we studied the
      immunolocalization of esVEGFR-2 in human embryos, infantile adrenal gland and
      primary NB. We also quantified esVEGFR-2 mRNA in NB cell lines after
      differentiation-induction by all-trans retinoic acid (ATRA). By immunoperoxidase
      staining we observed expression of esVEGFR-2 in both the sympathetic trunk and
      the adrenal medulla. Additionally, esVEGFR-2 was found in spinal ganglia, floor
      plate of the neural tube, choroid plexus, notochord, arterial endothelium,
      skeletal muscle, epidermis and gut epithelium. Developing and circulating
      leukocytes showed the strongest signal. In NB, esVEGFR-2 was considerably
      stronger in differentiating low grade tumours with neuronal phenotype than in
      undifferentiated lesions. Differentiation-induction of the NB cell line SMS-Kan
      with 5-10 uM ATRA resulted in a significant increase of esVEGFR-2 mRNA after 6, 9
      and 12 days. We show that esVEGFR-2 is widely expressed in embryonic tissues.
      Especially, the adrenal medulla and circulating leukocytes seem to be potent
      inhibitors of lymphangiogenesis. We provide additional evidence for a role of
      esVEGFR-2 in NB. Thereby, high levels of esVEGFR-2 correlate with a more
      differentiated phenotype, and may inhibit tumour progression by inhibition of
      lymphangiogenesis.

PMID- 22473694
TI  - The clinicopathological significance of REIC expression in colorectal carcinomas.
AB  - REIC is down-regulated in immortalized cell lines compared with the parental
      normal counterparts, and could inhibit colony formation, tumor growth and induce
      apoptosis. Here, its expression was examined by immunohistochemistry on tissue
      microarray containing colorectal non-neoplastic mucosa (NNM), adenoma and
      adenocarcinoma. Colorectal carcinoma tissue and cell lines were studied for REIC
      expression or its secretory level by Western blot, RT-PCR or enzyme-linked
      immunosorbent assay (ELISA). The results demonstrated that REIC was
      differentially expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM
      12, SW480, SW620, and WiDr with its secretion concentration less than 300 pg/mL.
      Carcinomas showed statistically lower REIC expression than matched NNM with no
      difference for protein content. Immunohistochemically, REIC expression was
      significantly decreased from NNM, adenoma to adenocarcinoma (p<0.05). REIC
      expression was negatively correlated with depth of invasion, TNM staging,
      dedifferentiation, Capase-3 and nuclear inhibitor of growth 5 (ING5) expression
      (p<0.05), while not with age, sex, tumor size, lymphatic or venous invasion, or
      lymph node metastasis (p>0.05). Kaplan-Meier analysis indicated that REIC
      expression was not associated with the prognosis of colorectal carcinomas
      (p>0.05). Cox's analysis demonstrated that lymphatic and venous invasion, lymph
      node metastasis, and UICC staging were independent prognostic factors for
      carcinoma (p<0.05). Our study indicated that down-regulated REIC expression might
      play an important role in colorectal adenoma-adenocarcinoma sequence and
      subsequent progression. Aberrant REIC expression might be employed as a good
      marker of pathogenesis and development of colorectal carcinomas.

PMID- 22473695
TI  - Influence of a hypercholesterolemic diet on the collagen composition of the
      bladder wall extracellular matrix in rats.
AB  - PURPOSE: To investigate the effects of hypercholesterolemic diet on the collagen
      composition of urinary bladder wall. MATERIALS AND METHODS: Forty-five female 4
      week-old Wistar rats were divided into three groups: 1) control group fed a
      normal diet (ND); 2) model of bladder outlet obstruction (BOO) group fed a ND;
      and 3) group fed a HCD (1.25% cholesterol). Total serum cholesterol, LDL
      cholesterol and body weight were assessed at baseline. Four weeks later, group 2
      underwent a surgical procedure resulting in a partial BOO, while groups 1 and 3
      underwent a sham similar surgical procedure. Six weeks later, all animals had
      their bladders removed; serum cholesterol and LDL cholesterol levels and body
      weights were measured. Morphological and morphometric analysis was performed by
      Picrosirius staining and collagen types I and III were identified by
      immunofluorescence. Statistical analysis was completed and significance was
      considered when p<0.05. RESULTS: Rats fed an HCD exhibited a significant increase
      in LDL cholesterol levels (p<0.001) and body weight (p=0.017), when compared to
      the groups fed a ND during the ten-week study period. Moreover, the HCD induced
      morphological alterations of the bladder wall collagen, regarding thin collagen
      fibers and the amounts of type III collagen when compared to the control group
      (p=0.002 and p=0.016, respectively), resembling the process promoted in the BOO
      model. CONCLUSIONS: A hyper-cholesterolemic diet in Wistar rats promoted
      morphological changes of the bladder types of collagen, as well as increases in
      body weight and LDL cholesterol.

PMID- 22473696
TI  - High-intensity exercise training produces morphological and biochemical changes
      in adrenal gland of mice.
AB  - The effects of training are dependent on complex, adaptive changes which are
      induced by acute physical exercise at different levels. In particular, evidence
      shows that the hypothalamus-pituitary-adrenocortical axis, as well as the
      sympatho-adrenomedullary system, is mainly involved in mediating the
      physiological effects of physical exercise. The aim of the present study was to
      investigate, through a morphological and biochemical approach, the effects of
      training on the adrenal gland of mice, following two different protocols
      consisting of either low- or high-intensity training. Mice were run daily on a
      motorised treadmill for 8 weeks, at a velocity corresponding to 60% (low
      intensity exercise) or 90% (high-intensity exercise) of the maximal running
      velocity previously determined by an incremental exercise test. We found that
      physical exercise produced an increase in the adrenal gland size compared with
      the control (sedentary) mice. The increase was 31.04% for mice that underwent
      high-intensity exercise and 10.08% for mice that underwent low intensity
      exercise, and this appeared to be the result of an increase in the area of both
      the adrenal cortex and adrenal medulla. Morphological analysis of the adrenal
      cortex showed that both types of exercise produced an increase in cytoplasmic
      vacuoles in steroidogenic cells, appearing more abundant after high-intensity
      exercise. No change was found in the reticulate zone. In the adrenal medulla,
      despite the absence of morphological changes, immunohistochemistry for tyrosine
      hydroxylase, dopamine beta-hydroxylase and phenyl-ethanolamine-N
      methyltransferase demonstrated an increased immunopositivity for these
      cathecolamine-synthesizing enzymes after intense exercise. These results were
      confirmed by immunoblot accompanied by densitometric analysis.

PMID- 22473697
TI  - Histological study of the protective effect of melatonin on neural cells after
      neonatal hypoxia-ischemia.
AB  - To minimize as much as possible the neurological consequences from hypoxic
      ischemic (HI) brain injury, neuroprotective strategies are urgently required. In
      this sense, there is growing interest in the neuroprotective potential of
      melatonin after perinatal asphyxia, due to its high efficacy, low toxicity and
      ready cross through the blood-brain barrier. Twenty six Wistar rats at postnatal
      day 7 were randomly assigned to: two hypoxic-ischemic groups: pups with the left
      common carotid artery ligated and then submitted to hypoxia (HI group) and
      animals that received a dose of 15 mg/kg melatonin just after the hypoxic
      ischemic event and repeated twice with an interval of 24 hours (HI+MEL group).
      Pups without ischemia or hypoxia were used as controls (Sham group). Seven days
      after surgery, brains were collected and coronal sections Nissl-stained, TUNEL
      labeled, or MBP- and GFAP-immunolabeled prior to determining brain infarct area,
      quantify surviving neurons and evaluate oligodendroglial injury and reactive
      astrogliosis. The number of surviving neurons showing a well preserved
      architecture in HI+MEL group was similar to that observed in the Sham group.
      Moreover, TUNEL-positive cells only appeared in the HI group. The ratio of left
      to-right hemispheric MBP immunostaining showed a significant decrease in the HI
      group in comparison with Sham pups, which was restored after melatonin
      administration. Melatonin also reduced reactive gliosis. Thus, our results
      suggest that treatment with melatonin after neonatal hypoxia-ischemia led to a
      neuroprotective effect reducing cell death, white matter demyelination and
      reactive astrogliosis.

PMID- 22473698
TI  - Molecular characterization of EGFR and EGFR-downstream pathways in triple
      negative breast carcinomas with basal like features.
AB  - AIMS: Triple negative breast cancer with basal like features (TN-BCBL) do not
      benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN
      BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an
      option. The characterization of EGFR and EGFR-downstream members may therefore
      provide important predictive information. METHODS AND RESULTS: Based on
      morphological and immunophenotypic features, we identified 38 TN-BCBLs that were
      subsequently investigated for alterations in EGFR signaling pathways. EGFR and
      PTEN protein levels were studied by immunohistochemistry, EGFR gene status by
      FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct
      sequencing. EGFR overexpression and loss of PTEN expression characterized the
      majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy
      number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene
      mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras
      and BRAF genes showed no mutations. Overall, out of 17 patients classified as
      FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway.
      CONCLUSIONS: These results provide evidence that the efficacy of anti-EGFR drugs
      in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN
      axis, and suggest that TN-BCBLs could benefit from tailored treatments against
      this axis.

PMID- 22473699
TI  - Histomorphometrical and proliferative aspects of placenta and uterus of the
      collared peccary (Tayassu tajacu).
AB  - The histomorphometric and proliferative characteristics of the collared peccary
      (Tayassu tajacu) placenta and uterus were analyzed. The material was examined by
      standard histological techniques and histochemistry (PAS, Perls and Alcian Blue
      pH 0.5 and 2.5%) and the cellular proliferation by AgNORs and flow cytometry. All
      the analyzed morphometric variables differed between pregnant and non-pregnant
      uteri in the luteal phase using the Dunnet test. Height and gland diameter of
      uterine glands increased linearly during pregnancy, with an intense positive PAS
      and Perls reaction in all stages. The cells with more than seven AgNORs per
      nuclei and the cells in the G2M cell cycle phase in the maternal tissue also
      increased after 70 days of pregnancy. The uteroplacental ridges had a linear
      increase in size with two distinct areas, base and top, with uterine epithelium
      and trophoblastic cells changing their morphology following the placental ridge
      development. Flow cytometry analysis showed the percentage of cells in each cell
      cycle phase with a quadratic behavior for stages G2/M in the maternal tissue,
      suggesting an increase in proliferative capacity of maternal tissue after 65 days
      of pregnancy. The same quadratic effect was observed in the G0/G1 phase in both
      maternal and fetal tissues. Cells in apoptosis showed cubic behavior in both
      tissues. The morphometric and cellular dynamic aspects observed in this study
      have not been previously described and they extend our knowledge of functions
      relating to maternal-fetal dynamics in this species.

PMID- 22473700
TI  - Telocytes form networks in normal cardiac tissues.
AB  - Telocytes (TC) are a class of interstitial cells present in heart. Their
      characteristic feature is the presence of extremely long and thin prolongations
      (called telopodes). Therefore, we were interested to see whether or not TCs form
      networks in normal cardiac tissues, as previously suggested.  Autopsy samples of
      cardiac tissues were obtained from 13 young human cadavers, without identifiable
      cardiac pathology and with a negative personal history of cardiovascular disease.
      Immunohistochemistry on formalin-fixed paraffin-embedded tissues was performed
      using monoclonal antibodies for CD117/c-kit. Additionally, ventricular samples
      from 5 Sprague-Dawley rats were ultrastructurally evaluated under transmission
      electron microscopy.  We found c-kit positive cells with TC features in
      subepicardium, as well in subepicardial arteries and in subepicardial fat. TCs
      were also present in the subendocardium. Light and electron microscopy revealed
      the existence of intramyocardial networks built up by bipolar TCs. Larger c-kit
      positive multipolar TCs were found between cardiac muscle bundles.   Our results
      support the existence of a cardiac network of telocytes.

PMID- 22473701
TI  - Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis
      of the European Prospective Investigation into Cancer and Nutrition (EPIC
      EURGAST) study after a longer follow-up.
AB  - In a previous European prospective investigation into cancer and nutrition (EPIC)
      analysis, we found an inverse association between total intake of vegetables,
      onion and garlic, and risk of intestinal gastric cancer (GC) and between citrus
      fruit and risk of cardia GC. The aim of this study is to reanalyze the effect of
      fruit and vegetables (F&V), based on a longer follow-up and twice the number of
      GC cases. Subjects are 477,312 men and women mostly aged 35 to 70 years
      participating in the EPIC cohort, including 683 gastric adenocarcinomas with 11
      years of follow-up. Information on diet and lifestyle was collected at baseline.
      A calibration study in a subsample was used to correct for dietary measurement
      errors. When comparing the highest vs. lowest quintile of intake, we found an
      inverse association between total intake of V&F and GC risk [hazard ratio (HR)
      0.77; 95% confidence interval (CI) 0.57-1.04; p for trend 0.02], between fresh
      fruit and risk of the diffuse type (HR 0.59; 95% CI 0.36-0.97; p for trend 0.03)
      and an inverse association between citrus fruit and risk of cardia cancer (HR
      0.61; 95% CI 0.38-1.00, p for trend 0.01). Although calibration revealed somewhat
      stronger inverse associations, none of the risks reached statistical
      significance. There was no association between total or specific vegetables
      intake and GC risk. The inverse association between fresh fruit and citrus fruits
      and risk of GC seems to be restricted to smokers and the Northern European
      countries. Fresh fruit and citrus fruit consumption may protect against diffuse
      and cardia GC, respectively.

PMID- 22473702
TI  - Rational construction of an extrinsic porous molecular crystal with an
      extraordinary high specific surface area.

PMID- 22473703
TI  - Antitrypanosomal properties of Panax ginseng C. A. Meyer: new possibilities for a
      remarkable traditional drug.
AB  - African trypanosomiasis is still a major health problem in many sub-Saharan
      countries in Africa. We investigated the effects of three preparations of Panax
      ginseng, Panax notoginseng, isolated ginsenosides, and the polyacetylene
      panaxynol on Trypanosoma brucei brucei and the human cancer cell line HeLa.
      Hexane extracts and the pure panaxynol were toxic and at the same time highly
      selective against T. b. brucei, whereas methanol extracts and 12 isolated
      ginsenosides were significantly less toxic and showed only weak selectivity.
      Panaxynol was cytotoxic against T. b. brucei at the concentration of 0.01 ug/mL
      with a selectivity index of 858, superior even to established antitrypanosomal
      drugs. We suggest that the inhibition of trypanothione reductase, which is only
      found in trypanosomes, might explain the observed selectivity. The high
      selectivity together with a cytotoxic concentration in the range of the
      bioavailability makes panaxynol and other polyacetylenes in general very
      promising lead compounds for the treatment of African trypanosomiasis.

PMID- 22473704
TI  - HMGB1 conveys immunosuppressive characteristics on regulatory and conventional T
      cells.
AB  - OBJECTIVE: The high-mobility group box-1 protein (HMGB1) serves as the prototypic
      damage-associated molecular pattern molecule, interacting with a variety of
      defined pattern recognition receptors in the microenvironment of damaged or
      necrotic tissue. As regulatory T cells (T(reg)) play a crucial role in autoimmune
      diseases and tumor immune escape, the previously unexamined role of HMGB1 on the
      function of T(reg) is of great interest. METHODS: Human CD4(+)CD25(+)CD127(-)
      T(reg) and CD4(+)CD25(-)CD127(+) conventional T cells (T(con)) were
      phenotypically analyzed for their constitutive as well as HMGB1-modulated
      expression of Toll-like receptors (TLR) and the receptor for advanced glycation
      end products (RAGE). Furthermore, the influence of recombinant and complexed
      HMGB1 from necrotic cell supernatant on the function of T(reg) and T(con) was
      investigated. RESULTS: T(reg) express significantly higher levels of RAGE on the
      cell surface than T(con), while levels of TLR4 are similar. HMGB1 modulates
      T(reg) biology by inducing migration and prolonging survival. Furthermore, HMGB1
      enhances IL-10 release and T(reg) suppressive capacity in a RAGE-dependent
      manner. In addition, HMGB1 directly suppresses IFNgamma release of T(con) and
      inhibits their proliferation via TLR4. CONCLUSION: HMGB1 directly enhances immune
      inhibitory functions of T(reg) via RAGE-mediated mechanisms and limits the number
      and activity of T(con). HMGB1 effects on T(reg) may alter immune reactivity in
      the setting of chronic inflammatory states such as cancer.

PMID- 22473705
TI  - Rab GTPases regulating receptor trafficking at the late endosome-lysosome
      membranes.
AB  - Lysosomes serve key degradative functions for the turnover of membrane lipids and
      protein components. Its biogenesis is principally dependent on exocytic traffic
      from the late endosome via the trans-Golgi network, and it also receives cargo to
      be degraded from the endocytic pathway. Membrane trafficking to the late endosome
      lysosome is tightly regulated to maintain the amplitude of signalling events and
      cellular homeostasis. Key coordinators of lysosomal traffic include members of
      the Rab small GTPase family. Amongst these, Rab7, Rab9 and the more recently
      studied Rab22B/31 have all been reported to regulate membrane trafficking
      processed at the late endosome-lysosome system. We discuss what is known about
      the roles of these Rab proteins and their interacting partners on the regulation
      of traffic of important receptor proteins such as the epidermal growth factor
      receptor (EGFR) and the mannose 6-phosphate receptor (M6PR), in association with
      the late endosome-lysosome system. Better knowledge of EGFR and M6PR traffic in
      this regard may aid in understanding the pathological processes, such as
      oncogenic transformations associated with these receptors.

PMID- 22473706
TI  - Effective expansion of human adipose-derived stromal cells and bone marrow
      derived mesenchymal stem cells cultured on a fragmin/protamine nanoparticles
      coated substratum with human platelet-rich plasma.
AB  - Fragmin/protamine nanoparticles (F/P NPs) can be stably coated onto plastic
      surfaces and used as a substratum for the absorption and controlled release of
      growth factors (GFs) secreted from human platelet-rich plasma (PRP). In this
      study, we investigated the capability of F/P NP-coated plates to act as a
      substratum for the proliferation of human adipose-derived stromal cells (ASCs)
      and bone marrow-derived mesenchymal stem cells (BMSCs) with GFs in PRP. Both cell
      types adhered well to the F/P NP-coated plates and grew optimally, with a
      doubling time of 30 and 32 h in low-concentration PRP (0.5%) medium supplemented
      with 5 ng/ml fibroblast growth factor-2 (FGF-2) on the F/P NP-coated plates.
      These cells maintained their multilineage potential for differentiation into
      adipocytes or osteoblasts. Furthermore, ASCs and BMSCs grew well in medium
      without PRP and FGF-2 on F/P NP-coated plates pretreated with PRP and FGF-2 in a
      concentration-dependent manner. Thus, F/P NP-coated plates are a useful
      substratum for the adherence and proliferation of ASCs and BMSCs in low
      concentration PRP medium supplemented with FGF-2. No xenogeneic serum is
      required.

PMID- 22473707
TI  - Possible involvement of brain-derived neurotrophic factor in eating disorders.
AB  - Eating disorders (EDs) manifest as abnormal patterns of eating behavior and
      weight regulation driven by low self-esteem due to weight preoccupation and
      perceptions toward body weight and shape. Two major groups of such disorders are
      anorexia nervosa (AN) and bulimia nervosa (BN). The etiology of EDs is complex
      and evidence indicates that both biological/genetic and psychosocial factors are
      involved. Several lines of evidence indicate that brain-derived neurotrophic
      factor (BDNF) plays a critical role in regulating eating behaviors and cognitive
      impairments in the EDs. BDNF is involved in neuronal proliferation,
      differentiation, and survival during development. BDNF and its tyrosine kinase
      receptor (TrkB) are expressed in hypothalamic nuclei associated with eating
      behaviors. A series of studies using BDNF knockout mice and the human BDNF gene
      indicate an association of BDNF and EDs with predisposition and vulnerability. In
      the previous studies, serum BDNF levels in subjects with EDs are reduced
      significantly compared with healthy controls, hence, we proposed that levels of
      serum BDNF would be a useful diagnostic indicator for EDs.

PMID- 22473708
TI  - Performance of sampling density-weighted and postfiltered density-adapted
      projection reconstruction in sodium magnetic resonance imaging.
AB  - Sampling density-weighted apodization projection reconstruction sequences are
      evaluated for three-dimensional radial imaging. The readout gradients of the
      sampling density-weighted apodization sequence are designed such that the locally
      averaged sampling density matches a Hamming filter function. This technique is
      compared with density-adapted projection reconstruction with nonfiltered and
      postfiltered image reconstruction. Sampling density-weighted apodization
      theoretically allows for a 1.28-fold higher signal-to-noise ratio compared with
      postfiltered density-adapted projection reconstruction sequences, if T(2)* decay
      is negligible compared with the readout duration T(RO). Simulations of the point
      spread functions are performed for monoexponential and biexponential decay to
      investigate the effects of T(2)* decay on the performance of the different
      sequences. Postfiltered density-adapted projection reconstruction performs
      superior to sampling density-weighted apodization for large T(RO)/T(2)* ratios
      [>1.36 (monoexponential decay); >0.35 (biexponential decay with T(2s)*/T(2f)* =
      10)], if signal-to-noise ratio of point-like objects is considered. In
      conclusion, it depends on the readout parameters, the T(2)* relaxation times, and
      the dimensions of the subject which of both sequences is most suitable.

PMID- 22473709
TI  - Control over the chemoselectivity of Pd-catalyzed cyclization reactions of (2
      iodoanilino)carbonyl compounds.
AB  - The factors that control the chemoselectivity of palladium-catalyzed cyclization
      reactions of (2-iodoanilino)carbonyl compounds have been explored by an extensive
      experimental computational (DFT) study. It was found that the selectivity of the
      process, that is, the formation of fused six- versus five-membered rings, can be
      controlled by the proper selection of the initial reactant, reaction conditions,
      and additives. Thus, esters or amides produce ketones by a nucleophilic addition
      process, whereas the addition of PhO(-)  ions leads to the formation of indolines
      by an alpha-arylation reaction. In contrast, the corresponding ketone reactants
      yield a mixture of both reaction products, the ratio of which depends on the base
      used, in the presence of phenol. The outcome of the processes can be explained by
      the formation of a common four-membered palladacycle intermediate from which the
      competitive nucleophilic addition and alpha-arylation reactions occur. The
      remarkable effect of phenol in the process, which makes the alpha-arylation
      reaction easier, favored the formation of enol complexes, which are stabilized by
      an intramolecular hydrogen bond between the hydroxy group of the enol moiety and
      the oxygen atom of the phenoxy ligand. Moreover, the chemoselectivy of the
      process can be also controlled by the addition of bidendate ligands that lead to
      the almost exclusive formation of indoles at expenses of the corresponding
      alcohols.

PMID- 22473710
TI  - Morvan syndrome: clinical and serological observations in 29 cases.
AB  - OBJECTIVE: A study was undertaken to describe the clinical spectrum, voltage
      gated potassium channel (VGKC) complex antibody specificities, and central
      nervous system localization of antibody binding in 29 patients diagnosed with
      Morvan syndrome (MoS). METHODS: Clinical data were collected using
      questionnaires. Radioimmunoassay, cell-based assays, and mouse brain
      immunohistochemistry were used to characterize the serum antibodies. RESULTS:
      Neuromyotonia (100%), neuropsychiatric features (insomnia 89.7%, confusion 65.5%,
      amnesia 55.6%, hallucinations 51.9%), dysautonomia (hyperhidrosis 86.2%,
      cardiovascular 48.3%), and neuropathic pain (62.1%) were the most common
      manifestations. A total of 93.1% of MoS patients were male. VGKC-complex
      antibodies were present in 23 of 29 (79%) MoS patients at referral; 24 of 27
      available sera had CASPR2, LGI1, or both CASPR2 and LGI1 antibodies (3 also with
      contactin-2 antibodies). CASPR2 antibodies were generally higher titer than LGI1
      antibodies. Tumors (41.4%), mainly thymomas, were associated with CASPR2
      antibodies and a poor prognosis, whereas LGI1 antibodies were associated with
      serum hyponatremia. In brain tissue regions including the hypothalamus, raphe,
      and locus coeruleus, commercial antibodies to LGI1 bound to neuronal cell bodies
      including the antidiuretic hormone-secreting and orexin-secreting hypothalamic
      neurons, whereas CASPR2 commercial antibodies bound more often to the neuropil.
      MoS antibodies bound similarly, but there was evidence of additional antibodies
      in some sera that were not adsorbed by LGI1- or CASPR2-expressing cells and bound
      to mouse Caspr2(-/-) tissue. INTERPRETATION: MoS is clinically distinct from
      other VGKC-complex antibody-associated conditions, and usually is associated with
      high-titer CASPR2 antibodies, often accompanied by lower-titer LGI1 antibodies.
      CASPR2 and LGI1 antibodies bind to multiple brain regions, which helps to explain
      the multifocal clinical features of this disease, but other antibodies are likely
      to play a role in some patients and need to be characterized in future studies.

PMID- 22473711
TI  - RNA-mediated gene assembly from DNA arrays.

PMID- 22473712
TI  - Regulation of alpha-synuclein expression in Down syndrome.
AB  - The triplication of genes located on chromosome 21 is known to cause a wide
      spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures,
      stroke, and mental retardation. Studies on RNA and protein expression of genes in
      DS brain have demonstrated the role of triplicated genes in several DS
      phenotypes. Significant changes in the expression of nontriplicated genes have
      also been observed. However, little information is available regarding the role
      of nonchromosome 21 genes in DS pathology. We have found that alpha-synuclein
      (SNCA), a presynaptic protein whose gene is located on chromosome 6 in the Ts65Dn
      mouse model for DS, is significantly reduced in the cortex and other brain
      regions. We hypothesize that this alteration may play a critical role in the
      reduced synaptic function observed in DS. We have found an increase in the level
      of neurosin, a key negative regulator of SNCA in Ts65Dn cortex. We have also
      found increased levels of protein phosphatase 2A, a negative regulator of the
      activation of tyrosine hydroxylase and a key enzyme in the biosynthetic pathway
      for dopamine in Ts65Dn cortex. These findings reveal potential target sites for
      intervention in the treatment of DS pathology.

PMID- 22473713
TI  - Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naive
      patients with chronic hepatitis C: a randomized phase II study.
AB  - Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural
      protein 3/4A protease inhibitor. The aim of the present phase II study was to
      examine virologic response rates with vaniprevir in combination with pegylated
      interferon alpha-2a (Peg-IFN-alpha-2a) plus ribavirin (RBV). In this double
      blind, placebo-controlled, dose-ranging study, treatment-naive patients with HCV
      genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-alpha
      2a (180 MUg/week) and RBV (1,000-1,200 mg/day) in combination with blinded
      placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600 mg once-daily
      [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-alpha-2a and RBV for an
      additional 44 weeks. The primary efficacy endpoint was rapid viral response
      (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses,
      vaniprevir was associated with a rapid two-phase decline in viral load, with HCV
      RNA levels approximately 3 log(10) IU/mL lower in vaniprevir-treated patients,
      compared to placebo recipients. Rates of RVR were significantly higher in each of
      the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus
      5.6%; P < 0.001 for all comparisons). There were numerically higher, but not
      statistically significant, early and sustained virologic response rates with
      vaniprevir, as compared to placebo. Resistance profile was predictable, with
      variants at R155 and D168 detected in a small number of patients. No relationship
      between interleukin-28B genotype and treatment outcomes was demonstrated in this
      study. The incidence of adverse events was generally comparable between
      vaniprevir and placebo recipients; however, vomiting appeared to be more common
      at higher vaniprevir doses. CONCLUSION: Vaniprevir is a potent HCV protease
      inhibitor with a predictable resistance profile and favorable safety profile that
      is suitable for QD or BID administration.

PMID- 22473714
TI  - Azospirillum improves lettuce growth and transplant under saline conditions.
AB  - BACKGROUND: Recent studies have shown that as a plant-growth-promoting
      rhizobacteria (PGPR), Azospirillum inoculation could contribute to the mitigation
      of the negative effects caused by salt on lettuce growth. Moreover, the use of
      PGPR to alleviate the effects of transplant in vegetables has also been
      recognized. However, the scarce data available on the use of Azospirillum to
      improve lettuce growth before and after transplant under saline conditions
      prompted us to focus our research on this topic. RESULTS: Early germination and
      seedling settlement of seeds exposed to 0 and 40 mol m(-3) NaCl were clearly
      improved by Azospirillum inoculation. At 0 mol m(-3) NaCl, plant establishment,
      leaf mass and root mass parameters before transplant were significantly higher in
      inoculated plants than in non-inoculated controls. At harvest, leaf fresh weight,
      ascorbic acid content and plant survival to transplant were also significantly
      higher in Azospirillum-inoculated plants grown at 0 mol m(-3) NaCl. In addition
      to these effects, leaf dry weight, area and chlorophyll content were also
      increased by Azospirillum inoculation when plants were grown at 40 mol m(-3)
      NaCl. CONCLUSION: Azospirillum-inoculated lettuce seeds yield a higher number of
      transplanted plants with superior quality than non-inoculated controls grown at 0
      or at 40 mol m(-3) NaCl.

PMID- 22473715
TI  - B7-H3 expression in colorectal cancer: nuclear localization strongly predicts
      poor outcome in colon cancer.
AB  - In colorectal cancer there is a need for molecular markers that can complement
      the histopathological staging in predicting the likelihood of disease recurrence
      following curatively intended surgery. B7-H3 is an immunoregulatory protein shown
      to be overexpressed in several cancer forms, often associated with more advanced
      disease and poor prognosis. We wanted to examine whether B7-H3 could be a
      potential prognostic marker in colorectal cancer. Paraffin-embedded samples from
      277 colorectal cancer patients were immunostained with anti-B7-H3 antibody. B7-H3
      was expressed in the tumor cell cytoplasm and cell membrane in 62% and 46% of the
      samples, respectively. Unexpectedly, B7-H3 was expressed in the nucleus in 30% of
      the tumors. The nuclear localization was confirmed by Western immunoblotting of
      subcellular fractions. Importantly, in colon cancer, nuclear B7-H3 expression was
      independently and significantly associated with reduced metastasis-free, disease
      specific and overall survival. B7-H3 expression in tumor-associated vasculature
      and fibroblasts was observed in the majority of samples, and endothelial B7-H3
      expression was also significantly associated with poor outcome in colon cancer.
      In rectal cancer patients, the only significant association was between
      fibroblast B7-H3 expression and shorter metastasis-free survival. Few significant
      associations to clinicopathological parameters were seen. The results indicate
      that nuclear B7-H3 might be involved in colon cancer progression and metastasis,
      and suggest that nuclear B7-H3 could become a useful prognostic marker in colon
      cancer.

PMID- 22473716
TI  - Comparative effectiveness of low-molecular-weight heparin versus unfractionated
      heparin for thromboembolism prophylaxis for medical patients.
AB  - BACKGROUND: Both unfractionated heparin (UFH) and low-molecular-weight heparin
      (LMWH) are approved for venous thromboembolism (VTE) prophylaxis. Which agent is
      superior remains controversial. OBJECTIVE: To compare the effectiveness,
      complications, and costs of UFH and LMWH as VTE prophylaxis for hospitalized
      medical patients. DESIGN: Retrospective cohort. SETTING: Three hundred thirty
      three acute care facilities in 2004-2005. PATIENTS: Adults with 4 common medical
      diagnoses considered to carry moderate-to-high risk of VTE. Excluded were
      patients on warfarin or with hospital stays of <= 2 days. VTE prophylaxis was
      assessed from billing data. INTERVENTION: None. MEASUREMENTS: VTE, major bleeding
      or heparin-induced thrombocytopenia, mortality, and cost. RESULTS: Of 32,104
      patients who received prophylaxis, 55% received LMWH and the remainder received
      UFH. The hospital where the patient obtained care was the strongest predictor of
      receiving LMWH. VTE was observed in 163 (0.51%) patients; complications, followed
      by stopping therapy, were rare (<0.2%). In analysis adjusted for the propensity
      for UFH and other covariates, patients treated with UFH had an odds ratio for VTE
      of 1.04 (95% confidence interval [CI] 0.76 to 1.43) compared to LMWH. In a
      grouped treatment model, the odds of VTE with UFH was 1.14 (95% CI 0.72 to 1.81).
      Adjusted odds of bleeding with UFH compared to LMWH were 1.64 (95% CI 0.50 to
      5.33), adjusted odds of complications followed by stopping prophylaxis were 2.84
      (95% CI 1.43 to 45.66), and adjusted cost ratio was 0.97 (95% CI 0.90 to 1.05).
      CONCLUSIONS: For VTE prophylaxis, the effectiveness and cost of LMWH and UFH are
      similar, but LMWH is associated with fewer complications.

PMID- 22473717
TI  - Examine before ordering: an algorithm unchanged by new tests.

PMID- 22473718
TI  - Glucocorticoid-induced diabetes and adrenal suppression.

PMID- 22473719
TI  - Glucocorticoid-induced diabetes and adrenal suppression.

PMID- 22473720
TI  - Essential tremor, beta-blockers, and calcium channel blockers.

PMID- 22473721
TI  - Parkinson disease.

PMID- 22473722
TI  - Q: Should I order an anti-CCP antibody test to diagnose rheumatoid arthritis?

PMID- 22473723
TI  - Purpuric lesion on the elbow.

PMID- 22473724
TI  - Purple urine in a woman with chronic kidney disease.

PMID- 22473725
TI  - Synthetic legal intoxicating drugs: the emerging 'incense' and 'bath salt'
      phenomenon.
AB  - Synthetic legal intoxicating drugs (SLIDs), such as those commonly contained in
      products sold over the counter as "bath salts" and "incense," have risen
      tremendously in popularity in the past few years. These drugs can have powerful
      adverse effects, including acute psychosis with delusions, hallucinations, and
      potentially dangerous, bizarre behavior.

PMID- 22473726
TI  - Factor V Leiden: how great is the risk of venous thromboembolism?
AB  - The factor V Leiden mutation, the most common inherited cause of thrombophilia,
      causes a mild hypercoagulable state. We describe a 29-year-old man, heterozygous
      for factor V Leiden, who developed extensive pulmonary emboli with concomitant
      bilateral deep venous thrombosis, likely provoked by prolonged immobility during
      a car trip. We then review the diagnosis, therapy, screening, and prognosis of
      venous thromboembolism related to factor V Leiden.

PMID- 22473727
TI  - Antireflux surgery in the proton pump inhibitor era.
AB  - Although proton pump inhibitors (PPIs) are now the first-line treatment for
      gastroesophageal reflux disease (GERD), surgery still has several specific
      indications. We review the current treatment of GERD and discuss how antireflux
      surgery fits into the overall scheme.

PMID- 22473728
TI  - A nodule on a woman's face.

PMID- 22473729
TI  - Nonallergic rhinitis: common problem, chronic symptoms.
AB  - Nonallergic rhinitis can significantly affect a patient's quality of life. It is
      difficult to distinguish from allergic rhinitis, but it has different triggers,
      and its response to treatment can vary. We review its differential diagnosis,
      causes, and treatment.

PMID- 22473730
TI  - Perspectives on intervening on physical inactivity and diet.

PMID- 22473731
TI  - A self-help coping intervention can reduce anxiety and avoidant health behaviours
      whilst waiting for cancer genetic risk information: results of a phase III
      randomised trial.
AB  - OBJECTIVE: The objective of this study is to evaluate the effectiveness of a self
      help coping intervention in reducing intrusive negative thoughts while waiting
      for cancer genetic risk information. METHODS: Between August 2007 and November
      2008, 1958 new referrals for cancer genetic risk assessment were invited to
      participate in a randomised trial. The control group received standard
      information. The intervention group received this information plus a written self
      help coping leaflet. The primary outcome measure was the intrusion subscale of
      the Impact of Event Scale. RESULTS: The intervention significantly reduced
      intrusive thoughts during the waiting period in those reporting moderate baseline
      levels of intrusion (p = 0.03). Following risk provision, those in the
      intervention group reporting low and moderate intrusive worries at baseline
      reported less intrusive thoughts than those in the control group (p = 0.04 and p
      = 0.03, respectively). The intervention had no adverse impact in the sample as a
      whole. Participants in the intervention group with high baseline avoidance and
      negative affect scores were significantly more likely to remain in the study than
      those in the control group (p = 0.05 and p = 0.004). CONCLUSIONS: Findings that
      the intervention both reduced distress in those with moderate levels of distress
      and had no adverse effects following notification of cancer genetic risk suggest
      that this simple intervention can be implemented across a range of oncology
      settings involving periods of waiting and uncertainty. The intervention may also
      reduce the number of individuals dropping out of cancer genetic risk assessment
      or screening. However, those with clinically high levels of psychological
      distress are likely to require a more intensive psychological intervention.

PMID- 22473732
TI  - [Malnutrition and weight loss - nurse assessment of nutritional status and
      counselling: experiences of patients with newly diagnosed or relapsed cancer].
AB  - Due to the anorexia-cachexia syndrome, cancer patients are already suffering from
      nutritional problems and weight loss by the time they receive their diagnosis and
      start chemotherapy. In the oncology outpatient clinic of a Swiss university
      hospital, patients currently undergo a nutritional assessment and receive
      individual counselling at the beginning of cancer treatment. This qualitative
      study explored cancer patients' experiences with weight loss and nutritional
      problems as well as how they experienced the assessment and the consecutive
      counselling by nurses. Interviews were conducted with 12 patients and qualitative
      content analysis was used for data analysis. Results showed that patients barely
      registered the weight loss and did not interpret it as an early warning signal.
      Nevertheless, they attempted to improve their nutritional habits soon after
      diagnosis, prior to receiving any counselling. The patients did not experience
      the assessment as troublesome. They appreciated the nurses' advice and
      implemented the suggestions they found appropriate. This study highlights the
      importance of patient education regarding weight loss and nutritional problems
      early in the course of an illness. Patients may not be aware of nutritional
      problems at this early stage and may lack the necessary specialised knowledge.
      Assessment and counselling provided by nurses offer targeted measures for
      prevention of malnutrition and weight loss.

PMID- 22473733
TI  - [Improvement of oral health care in geriatric care by training of nurses and
      nursing assistants for the elderly].
AB  - Because oral health among residents of German nursing homes is inadequate, this
      intervention study evaluated the effects of dental training for nurses and
      nursing assistants (RN and RA) in homes for the elderly on their assessment of
      oral health in residents and, as a consequence, on the status of residents' oral
      health. 53 residents and the RNs and RAs from three homes for the elderly
      participated in this study. The nursing staff received training in dental health
      care. As primary outcome, the competence in performing the Brief Oral Health
      Examination (BOHSE) was measured at baseline date and four months after training.
      Additional outcome measures were dental and denture hygiene in residents,
      functional status of dentures, and treatment needs. Dental training was shown to
      improve the nursing staff's competences in oral health assessment in tendency.
      Residents' oral hygiene improved significantly, whereas no relevant effects on
      hygiene and functional status of dentures were registered. The need for dental
      treatment turned out to be considerable at both measurements. Modifications in
      test tools with identification of dental treatment needs seem to be indicated in
      order to improve cooperation between nursing staff and dentists in homes for the
      elderly.

PMID- 22473734
TI  - [School nursing in Germany? - A review about tasks and roles of School Nurses].
AB  - For many decades, nurses especially in Anglo-American and Scandinavian countries
      have operated as "School (Health) Nurses" and have supervised children and
      teenagers in all health-related matters. This review applies to the question
      which specific tasks and roles School Nurses fulfil in these countries and which
      of the tasks in Germany also could be carried out by adequately qualified nurses.
      34 articles were found by systematic literature search which focused on general
      descriptions of the roles and tasks of School Nurses. Overall, eleven central
      fields of duties could be identified. They included the treatment of injuries,
      acute and chronic illnesses, emergency care, preventive and health-promoting
      activities, information, education and counselling, the assessment of health
      related problems and needs, the development and implementation of appropriate
      services as well as the fields: communication, cooperation and management of
      supply. With a view to the positive international experiences, the implementation
      of School Nurses in Germany seems to be a promising approach to promote both
      health and educational goals. Therefore, an additional university qualification
      "School Nursing" based on the existing international curricula is required.

PMID- 22473735
TI  - [Serving without end. The historical development of the work schedule in nursing
      in Germany].

PMID- 22473737
TI  - [Theory distant evidence basis? Response to the contribution of Moers et al.,
      Pflege, December 2011, issue 6. Topic focused theory development issue in nursing
      of the 21st century].

PMID- 22473738
TI  - [The psychosocial needs of women with breast cancer and their family].

PMID- 22473739
TI  - GDNF overexpression fails to provoke muscle recovery from botulinum toxin
      poisoning: a preliminary study.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has potent axonal growth and
      survival effects on motoneurons. This study used transgenic Myo-GDNF mice to
      assess the effects of targeted GDNF overexpression on functional recovery after
      botulinum toxin type A (BTxA) chemodenervation. BTxA (0.1 U) was injected into
      the tibialis anterior (TA) muscle of wild-type CF1 and transgenic Myo-GDNF mice.
      On days 1, 7, 14, and 21 after injection, evoked muscle force production and
      muscle mass were measured (n = 6, for each group at each time point). Greater
      maximal tetanic force and calculated specific force were evoked in Myo-GDNF
      animals when compared with control CF1 animals at days 1, 7, and 21. However, the
      differences were not statistically significant. Similarly, modest reductions in
      muscle atrophy in the Myo-GDNF group at all time points were not statistically
      significant. Targeted overexpression of GDNF in the muscles of Myo-GDNF mice did
      not improve motor recovery in the first 21 days after BTxA chemodenervation.

PMID- 22473740
TI  - Decreased tumstatin-mRNA is associated with poor outcome in patients with NSCLC.
AB  - Tumstatin is a candidate tumor suppressor that plays an important role in tumor
      growth and angiogenesis. The purpose of this study was to evaluate the
      correlation between tumstatin-mRNA expression and the clinicopathologic
      characteristics, tumor angiogenesis, outcome of patients with non-small cell lung
      cancer (NSCLC). Specimens from 68 patients with NSCLC were recruited in this
      study. Tumstatin-mRNA expression and protein level in tumor tissues were
      quantified respectively by quantitative RT-PCR and ELISA. Microvessel density
      (MVD) was determined by CD34 immunostaining. The correlation of tumstatin-mRNA
      expression levels with clinicopathologic variables, tumor angiogenesis, and
      prognosis was analyzed. Tumstatin-mRNA expression levels were decreased in tumor.
      Tumstatin-mRNA expression level was significantly correlated with its protein
      level in tumor (r = 0.562; P = 0.001). Tumstatin-mRNA expression levels in poorly
      differentiated tumor tissues were significantly lower than in well-differentiated
      tumor tissues (P < 0.004). Furthermore, tumor tumstatin-mRNA expression were also
      significantly related to tumor pathologic stage (P = 0.032) and MVD (r = -0.77, P
      < 0.0001). Overall survival (OS) and disease-free survival (DFS) analysis
      indicated that NSCLC patients with low tumstatin-mRNA expression had poorer OS
      and DFS than those with high expression (P = 0.015 and 0.037; respectively).
      Multivariable Cox regression analysis revealed that the tumstatin-mRNA expression
      could be an independent prognostic indicators in both DFS and OS. Tumstatin-mRNA
      expression levels are down-regulated in NSCLC tissues. Tumstatin-mRNA expression
      level correlates with prognosis, which suggests that tumstatin-mRNA is a new
      potential independent marker of favorable prognosis in NSCLC.

PMID- 22473741
TI  - Matrix formation is enhanced in co-cultures of human meniscus cells with bone
      marrow stromal cells.
AB  - The ultimate aim of this study was to assess the feasibility of using human bone
      marrow stromal cells (BMSCs) to supplement meniscus cells for meniscus tissue
      engineering and regeneration. Human menisci were harvested from three patients
      undergoing total knee replacements. Meniscus cells were released from the menisci
      after collagenase treatment. BMSCs were harvested from the iliac crest of three
      patients and were expanded in culture until passage 2. Primary meniscus cells and
      BMSCs were co-cultured in vitro in three-dimensional (3D) pellet culture at three
      different cell-cell ratios for 3 weeks under normal (21% O2 ) or low (3% O2 )
      oxygen tension in the presence of serum-free chondrogenic medium. Pure BMSCs and
      pure meniscus cell pellets served as control groups. The tissue generated was
      assessed biochemically, histochemically and by quantitative RT-PCR. Co-cultures
      of primary meniscus cells and BMSCs resulted in tissue with increased (1.3-1.7
      fold) deposition of proteoglycan (GAG) extracellular matrix (ECM) relative to
      tissues derived from BMSCs or meniscus cells alone under 21% O2 . GAG matrix
      formation was also enhanced (1.3-1.6-fold) under 3% O2 culture conditions. Alcian
      blue staining of generated tissue confirmed increased deposition of GAG-rich
      matrix. mRNA expression of type I collagen (COL1A2), type II collagen (COL2A1)
      and aggrecan were upregulated in co-cultured pellets. However, SOX9 and HIF
      1alpha mRNA expression were not significantly modulated by co-culture. Co-culture
      of primary meniscus cells with BMSCs resulted in increased ECM formation. Co
      delivery of meniscus cells and BMSCs can, in principle, be used in tissue
      engineering and regenerative medicine strategies to repair meniscus defects.

PMID- 22473742
TI  - Rapid time-resolved magnetic resonance angiography via a multiecho radial
      trajectory and GraDeS reconstruction.
AB  - Contrast-enhanced magnetic resonance angiography is challenging due to the need
      for both high spatial and temporal resolution. A multishot trajectory composed of
      pseudo-random rotations of a single multiecho radial readout was developed. The
      trajectory is designed to give incoherent aliasing artifacts and a relatively
      uniform distribution of projections over all time scales. A field map (computed
      from the same data set) is used to avoid signal dropout in regions of substantial
      field inhomogeneity. A compressed sensing reconstruction using the GraDeS
      algorithm was used. Whole brain angiograms were reconstructed at 1-mm isotropic
      resolution and a 1.1-s frame rate (corresponding to an acceleration factor >
      100). The only parameter which must be chosen is the number of iterations of the
      GraDeS algorithm. A larger number of iterations improves the temporal behavior at
      cost of decreased image signal-to-noise ratio. The resulting images provide a
      good depiction of the cerebral vasculature and have excellent arterial/venous
      separation.

PMID- 22473743
TI  - Short sleep duration and obesity: mechanisms and future perspectives.
AB  - A reduction of sleep time has become common over the last century, and growing
      evidence from both epidemiological and laboratory-based studies suggests sleep
      curtailment is a new risk factor for the development of obesity. On this basis,
      the present review examines the role of sleep curtailment in the metabolic and
      endocrine alterations, including decreased glucose tolerance and insulin
      sensitivity, increased evening concentrations of cortisol, increased levels of
      ghrelin, decreased levels of leptin and increased hunger and appetite. It will be
      discussed how sleep restriction may lead to increase in food intake and result in
      greater fatigue, which may favour decreased energy expenditure. Altogether,
      evidences point to a possible role of decreased sleep duration in the current
      epidemic of obesity and therefore present literature highlights the importance of
      getting enough good sleep for metabolic health. Many aspects still need to be
      clarified and intervention studies also need to be conducted.

PMID- 22473744
TI  - Mu, delta, and kappa opioid receptor agonists induce peripheral antinociception
      by activation of endogenous noradrenergic system.
AB  - Opioid receptor agonists induce noradrenaline release in the supraspinal, spinal,
      and peripheral sites. Endogenous noradrenaline release can induce an
      antinociceptive effect by activation of the alpha(2) adrenoceptor. This
      interaction between the opioid and the adrenergic systems could be the
      alternative mechanism by which opioid receptor agonists mediate peripheral
      antinociception. Therefore, the aim of the present study was to verify whether
      peripheral antinociception induced by the MU, delta, and kappa opioid receptor
      agonists DAMGO, SNC80, and bremazocine, respectively, through the endogenous
      noradrenergic system. All drugs were administered locally into the right hind paw
      of male Wistar rats. The rat paw pressure test was used, with hyperalgesia
      induced by intraplantar injection of prostaglandin E(2). DAMGO, SNC80, or
      bremazocine elicited local dose-dependent peripheral antinociception. This
      peripheral effect was antagonized by the nonselective alpha(2) adrenoceptor
      antagonist yohimbine and by the selective alpha(2C) adrenoceptor antagonist
      rauwolscine but not by the selective antagonists for alpha(2A), alpha(2B), and
      alpha(2D) adrenoceptor subtypes (BRL 44 480, imiloxan, and RX 821002,
      respectively). The opioid-induced effect was antagonized by the nonselective
      alpha(1) adrenoceptor antagonist prazosin and by the nonselective beta
      adrenoceptor antagonist propranolol. Guanethidine, a depletor of peripheral
      sympathomimetic amines, restored approximately 50-60% of the opioid-induced
      peripheral antinociception. Furthermore, acute injection of the noradrenaline
      reuptake inhibitor reboxetine intensified the antinociceptive effects of low-dose
      DAMGO, SNC80, or bremazocine. This study provides evidence that DAMGO, SNC80, or
      bremazocine induces peripheral antinociception by noradrenaline release and
      interaction with adrenoceptors.

PMID- 22473745
TI  - Thiols screened by the neocarzinostatin protein for preserving or detoxifying its
      bound enediyne antibiotic.
AB  - Neocarzinostatin is an antibiotic chromoprotein produced by Streptomyces
      carzinostaticus. Its enediyne-containing chromophore exhibits high DNA cleavage
      activity and belongs to one of the most potent categories of antitumor agents.
      The labile chromophore is readily inactivated by environmental thiols including
      the most abundant glutathione. How the microorganism preserves the secreted
      antibiotic and at the same time is immune to its toxicity are of interest. Site
      directed mutagenesis studies of the neocarzinostatin protein have shown that
      residues D33 and D99 play primary and secondary roles, respectively, in
      preserving neocarzinostatin from acidic glutathione whereas D79 and other
      residues around the opening of the binding cleft have an insignificant effect.
      Biothiol analyses revealed that cells of S. carzinostaticus produced no
      glutathione, but instead neutral mycothiol, which is known to serve functions
      analogous to glutathione. Mycothiol was the only neutral-charged thiol produced
      by the organism; all other identified biothiols carried at least partial negative
      charges. When the bacteria were cultured under conditions that stimulated the
      biosynthesis of neocarzinostatin, the yield of mycothiol increased significantly,
      which suggests mycothiol-dependent cellular detoxification. Treating
      neocarzinostatin samples with the cell extract that retained active sulfhydryls
      led to efficient drug inactivation, which indicates that mycothiol is allowed to
      approach the protein-bound chromophore. The anionic side-chains of D33 and D99 in
      the neocarzinostatin protein played two critical roles in a single thiol
      screening operation: Preserving the antibiotic for defense and survival by
      rejecting the ubiquitous glutathione through charge-charge repulsion in the outer
      cell environment and detoxifying the toxin in the inner-cell body for self
      resistance by accepting the cell-produced neutral mycothiol.

PMID- 22473746
TI  - PEGylation of an artificial O2 and CO receptor: synthesis, characterisation and
      pharmacokinetic study.
AB  - A synthetic oxygen (O(2)) and carbon monoxide (CO) receptor (hemoCD) composed of
      5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron(ii) and a per-O-methylated
      beta-cyclodextrin dimer with a pyridine linker (Py3CD) was functionalised with
      poly(ethylene glycol) (PEG) to elongate the circulation time of the receptor in
      the bloodstream. alpha-PEG monocarboxylic acid (HOOC(CH(2))(3)(CO)O-PEG(mw)
      OCH(3); mw = 750 or 5k) or alpha,omega-PEG dicarboxylic acid (HOOC(CH(2))(3)(CO)O
      PEG(mw)-O(CO)(CH(2))(3)COOH; mw = 10k or 20k) was reacted with the amino group of
      5-(4-aminophenyl)-10,15,20-tris(4-sulfonatophenyl)porphyrin to afford a porphyrin
      monomer having a PEG chain or a porphyrin dimer having a PEG linker,
      respectively. The ferrous complexes of these PEGylated porphyrins (PEG750-, PEG5k
      , PEG10k- and PEG20k-hemoCDs) bound O(2) in aqueous solution, P(1/2) values being
      6.5-8.1 Torr at pH 7.0 and 25  degrees C. Each PEG(mw)-hemoCD was infused into
      the femoral vein of a Wistar male rat. After 6 h of the infusions, 67, 82, 86 and
      42% of PEG750-, PEG5k-, PEG10k- and PEG20k-hemoCD were excreted in the urine.
      PEG750-hemoCD with a hydrodynamic diameter (D(h)) of 3.4 nm seemed to partly leak
      from the blood vessels (pore size: 2-6 nm) before renal filtration (pore size: 4
      14 nm). PEG5k- (D(h) = 6.2 nm) and PEG10k-hemoCDs (9.0 nm) hardly passed through
      the blood vessels but were fully filtered by the kidney, resulting in high
      excretion rates. A considerable amount of PEG20k-hemoCD (D(h) = 12.0 nm) was
      retained in the blood even at 6 h after administration. The present study
      demonstrates that the behaviour of hemoCD in blood after administration can be
      controlled by modification of hemoCD with PEG having an appropriate molecular
      weight.

PMID- 22473747
TI  - A bulky biaryl phosphine ligand allows for palladium-catalyzed amidation of five
      membered heterocycles as electrophiles.

PMID- 22473748
TI  - Assessing bioequivalence of generic antiepilepsy drugs by indirect comparisons.

PMID- 22473749
TI  - Interleukin-22 induces hepatic stellate cell senescence and restricts liver
      fibrosis in mice.
AB  - Interleukin (IL)-22 is known to play a key role in promoting antimicrobial
      immunity, inflammation, and tissue repair at barrier surfaces by binding to the
      receptors, IL-10R2 and IL-22R1. IL-22R1 is generally thought to be expressed
      exclusively in epithelial cells. In this study, we identified high levels of IL
      10R2 and IL-22R1 expression on hepatic stellate cells (HSCs), the predominant
      cell type involved in liver fibrogenesis in response to liver damage. In vitro
      treatment with IL-22 induced the activation of signal transducer and activator of
      transcription (STAT) 3 in primary mouse and human HSCs. IL-22 administration
      prevented HSC apoptosis in vitro and in vivo, but surprisingly, the
      overexpression of IL-22 by either gene targeting (e.g., IL-22 transgenic mice) or
      exogenous administration of adenovirus expressing IL-22 reduced liver fibrosis
      and accelerated the resolution of liver fibrosis during recovery. Furthermore, IL
      22 overexpression or treatment increased the number of senescence-associated beta
      galactosidase-positive HSCs and decreased alpha-smooth muscle actin expression in
      fibrotic livers in vivo and cultured HSCs in vitro. Deletion of STAT3 prevented
      IL-22-induced HSC senescence in vitro, whereas the overexpression of a
      constitutively activated form of STAT3 promoted HSC senescence through p53- and
      p21-dependent pathways. Finally, IL-22 treatment up-regulated the suppressor of
      cytokine signaling (SOCS) 3 expression in HSCs. Immunoprecipitation analyses
      revealed that SOCS3 bound p53 and subsequently increased the expression of p53
      and its target genes, contributing to IL-22-mediated HSC senescence. CONCLUSION:
      IL-22 induces the senescence of HSCs, which express both IL-10R2 and IL-22R1,
      thereby ameliorating liver fibrogenesis. The antifibrotic effect of IL-22 is
      likely mediated by the induction of HSC senescence, in addition to the previously
      discovered hepatoprotective functions of IL-22.

PMID- 22473750
TI  - Pancreatic lipase inhibitory activity of phlorotannins isolated from Eisenia
      bicyclis.
AB  - Pancreatic lipase is a potential therapeutic target for the treatment of diet
      induced obesity in humans. In an ongoing search for new pancreatic lipase
      inhibitors from natural sources, a methanolic extract of marine brown algae,
      Eisenia bicyclis, showed a significant inhibitory effect against pancreatic
      lipase. Bioassay-guided isolation of this methanolic extract using a pancreatic
      lipase inhibitory assay led to the isolation and identification of six known
      phlorotannins: eckol (1), fucofuroeckol A (2), 7-phloroeckol (3),
      dioxindehydroeckol (4), phlorofucofuroeckol A (5), and dieckol (6). The
      structures were established on the basis of nuclear magnetic resonance and mass
      spectrometry spectroscopic data interpretation. Among the isolated phloroglucinol
      polymers, compounds 2 and 3 showed potent inhibitory effects on pancreatic lipase
      with IC50 values ranging from 37.2 +/- 2.3 to 12.7 +/- 1.0 MUM, respectively.

PMID- 22473751
TI  - Virgin olive oil phenolic profile and variability in progenies from olive
      crosses.
AB  - BACKGROUND: The progressive transformation of olive growing and the increasing
      demands for high-quality monovarietal virgin olive oil (VOO) have triggered
      interest in olive breeding programs, in which the evaluation of the new genotypes
      is the basis for obtaining new olive cultivars. In this work, the phenolic
      composition of VOOs from two progenies from crosses between 'Arbequina',
      'Arbosana' and 'Sikitita' has been evaluated along two years. RESULTS: A higher
      degree of variation was observed in segregating population as compared to
      genitors. The results also showed that the variability within crosses constitutes
      the major contribution to total variance for all considered parameters (>92% of
      total sum of squares). All compounds under study were present in oils obtained in
      both years; however, clear differences in their concentrations were observed
      between years. CONCLUSION: Olive breeding can indeed provide genotypes that
      produce oils with improved phenolic profiles as compared to traditional
      cultivars. In addition, the data showed that selection as a function of tyrosol
      content could be achieved in only one crop year. Finally, p-coumaric acid was the
      unique component able to discriminate between both crop years under study.

PMID- 22473752
TI  - Oligothiophene cruciform with a germanium spiro center: a promising material for
      organic photovoltaics.

PMID- 22473753
TI  - Being within or being between? The cultural context of Arab women's experience of
      coping with breast cancer in Israel.
AB  - BACKGROUND: Coping with cancer is affected by cultural norms, beliefs, and
      perceptions. To date, only a few studies have examined how Arab women cope with
      breast cancer and how the illness affects their lives. We aimed to study how Arab
      women perceive and ascribe meaning to their illness and its personal, familial,
      and social implications and to examine their coping strategies within the
      religious and traditional cultural context. METHODS: The study was qualitative.
      Participants were 20 Muslim and Christian Arab women with breast cancer (stages I
      III) from northern Israel, aged 20-50 years. Participants were between 1 and 5
      years after chemotherapy and radiotherapy. In-depth, semi-structured interviews
      were conducted and later transcribed. RESULTS: Four main themes emerged: (i)
      "Family Comes First": The Woman and Her Family; (ii) To Expose or not to Expose?
      That's the Dilemma; (iii) Faith in God as a Source of Coping; and (iv)
      Constructing New Meanings Following Recovery from Cancer. Findings stressed a
      duality in participants' cancer coping experience according to the traditional
      cultural norms of concealment, while simultaneously encountering more open
      Western attitudes through interactions with healthcare providers and Jewish women
      receiving treatment alongside them. CONCLUSIONS: Healthcare professionals should
      be aware of the unique implications of cancer in the context of the traditional
      Arab culture intertwined with modernization processes. This context calls for
      interventions that consider the understandings depicted in the present study.

PMID- 22473755
TI  - The 19S proteasome subunit Rpn7 stabilizes DNA damage foci upon genotoxic insult.
AB  - The DNA damage response (DDR) orchestrates the recruitment of repair proteins at
      sites of damage and arrests cell-cycle progression until completion of repair.
      Upon irreparable damage, DNA damage foci persist (long-lived foci) and this is
      believed to induce cellular senescence. The resolution of DNA damage foci has
      previously been shown to depend on proteasomal degradation and various proteasome
      subunits have been implicated in the DDR. In this study, we aimed to analyze the
      possible distinct roles of individual proteasome subunits in the DDR. We show
      that specific 19S subunits respond to DNA damage by increased protein levels and
      nuclear translocation. Importantly, two 19S subunits, Rpn7 and Rpn11, colocalize
      with DNA damage foci over their whole lifespan. Although silencing of Rpn11 does
      not affect foci stability and lifespan, silencing of Rpn7 promotes faster
      resolution of DNA damage foci following genotoxic insult. For the first time, we
      provide evidence that Rpn7 silencing specifically decreases the frequencies of
      long-lived DNA damage foci without, however, affecting the repair rate of short
      lived foci. Therefore, we propose that interaction of Rpn7 with DDR foci in situ
      mediates the protection of DNA damage foci from premature resolution. We suggest
      that this interaction is involved in enabling cellular senescence following
      genotoxic insult.

PMID- 22473754
TI  - Predictors of medication adherence postdischarge: the impact of patient age,
      insurance status, and prior adherence.
AB  - BACKGROUND: Optimizing postdischarge medication adherence is a target for
      avoiding adverse events. Nevertheless, few studies have focused on predictors of
      postdischarge medication adherence. METHODS: The Pharmacist Intervention for Low
      Literacy in Cardiovascular Disease (PILL-CVD) study used counseling and follow-up
      to improve postdischarge medication safety. In this secondary data analysis, we
      analyzed predictors of self-reported medication adherence after discharge. Based
      on an interview at 30-days postdischarge, an adherence score was calculated as
      the mean adherence in the previous week of all regularly scheduled medications.
      Multivariable linear regression was used to determine the independent predictors
      of postdischarge adherence. RESULTS: The mean age of the 646 included patients
      was 61.2 years, and they were prescribed an average of 8 daily medications. The
      mean postdischarge adherence score was 95% (standard deviation [SD] = 10.2%). For
      every 10-year increase in age, there was a 1% absolute increase in postdischarge
      adherence (95% confidence interval [CI] 0.4% to 2.0%). Compared to patients with
      private insurance, patients with Medicaid were 4.5% less adherent (95% CI -7.6%
      to -1.4%). For every 1-point increase in baseline medication adherence score, as
      measured by the 4-item Morisky score, there was a 1.6% absolute increase in
      postdischarge medication adherence (95% CI 0.8% to 2.4%). Surprisingly, health
      literacy was not an independent predictor of postdischarge adherence.
      CONCLUSIONS: In patients hospitalized for cardiovascular disease, predictors of
      lower medication adherence postdischarge included younger age, Medicaid
      insurance, and baseline nonadherence. These factors can help predict patients who
      may benefit from further interventions.

PMID- 22473756
TI  - Elevated serum IL-16 and RANTES levels in patients with autoimmune thyroid
      diseases and modulation by methimazole therapy.
AB  - Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell
      expressed and secreted) are 2 cytokines with the function of T helper cell
      recruitment, which might play a key role in pathogenesis of autoimmune thyroid
      diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in
      patients with AITD. Serum IL-16 and RANTES levels were measured in patients with
      Graves' disease (GD; n=45), Hashimoto's thyroiditis (HT; n=68), nontoxic
      multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results
      showed that serum IL-16 and RANTES levels were elevated both in HT and higher in
      untreated GD patients when compared to NTMNG patients and the healthy
      individuals, which were decreased after MMI therapy in untreated GD patients.
      However, in HT patients, serum IL-16 and RANTES levels were comparable among the
      conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and
      untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3,
      FT4, TRAb in GD, but not in HT patients. The data did not show any correlation
      between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might
      be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe
      a potential marker of disease activity and severity.

PMID- 22473757
TI  - Differential response of the primate HPG axis to N-methyl-D, L-aspartate, but not
      to Kisspeptin challenge under euglycemic and hypoglycemic conditions.
AB  - Hypoglycemia inhibits the hypothalamic-pituitary-gonadal (HPG) axis by still
      incompletely deciphered mechanisms. Many evidences suggest that the hypoglycemia
      induced inhibition of the HPG axis involves alteration of the hypothalamic
      gonadotropin-releasing hormone (GnRH) release, but neuroendocrine factors
      responsible for this alteration are yet to be completely elucidated. The current
      study was carried out to ascertain whether insulin-induced hypoglycemic
      suppression of the HPG axis involves modulation of responsiveness of the GnRH
      neuron to kisspeptin and excitatory amino acids (EAA) drives. Five intact chair
      restraint habituated adult male rhesus monkeys (Macaca mulatta) were given
      intravenous boli of GnRH, hCG, human kisspeptin-10 (KP10), NMDA (N-methyl-D, L
      aspartate, an EAA analogue), and vehicle in both insulin (1 IU/kg)-induced
      hypoglycemic (IIH) and normal euglycemic conditions. Specific RIAs were used for
      measuring plasma cortisol and T concentrations. KP10 and NMDA administration
      stimulated significantly (p<0.005) T secretion in both euglycemic and
      hypoglycemic monkeys. Mean post-KP10 T concentrations and AUC were comparable
      between euglycemic and hypoglycemic monkeys. However, mean post-NMDA T levels and
      AUC in hypoglycemic animals were significantly lower (p<0.01-0.005) as compared
      to the corresponding values in euglycemic animals. T response to GnRH and hCG was
      similar between hypoglycemic and euglycemic monkeys. Vehicle did not affect
      plasma T concentrations in all conditions. Our results demonstrate that while the
      primate HPG axis response to kisspeptin stimulation remains intact that to EAA
      excitation is attenuated in hypoglycemic conditions, suggesting that hypogonadism
      in IIH is contributed, in part, by reduced sensitivity of the GnRH neurons to EAA
      signaling in the primate hypothalamus.

PMID- 22473758
TI  - Efficacy and safety of long term treatment of unresponsive hypoparathyroidism
      using multipulse subcutaneous infusion of teriparatide.
AB  - Vitamin D nonresponsive hypoparathyroidism is uncommonly seen in the clinical
      practice. The use of new treatment modalities, including teriparatide
      administration, provides an alternative requiring its validation. We report the
      first case of hypoparathyroidism refractory to vitamin D that was successfully
      controlled for 5 years by teriparatide treatment. A 53-year-old woman presented
      severe hypoparathyroidism after thyroidectomy. No therapeutic response was
      obtained with oral and i. v. calcium and magnesium, or even with 5 MUg
      calcitriol/day. Digestive disorders were ruled out and heterologous parathyroid
      transplant was ineffective. Subcutaneous (s. c.) recombinant human PTH 1-34
      (rhPTH-teriparatide) plus oral calcitriol, calcium, and magnesium, were partially
      effective, but effectiveness of 20 MUg teriparatide lasted less than 4 h and
      stable calcemia was not possible even with 4-6 injections/day. Multipulse s. c.
      pump driven infusion of teriparatide achieved complete normalization of serum
      calcium, phosphate, magnesium, calciuria, and magnesuria with relatively low
      teriparatide doses (25-35 MUg/day) after the first day of treatment.
      Effectiveness of this treatment modality was maintained for 5 years. The only
      significant side effect observed during these years was the development of
      subcutaneous nodules with occasional insufficient control of calcemia. A gain in
      bone mineral density was observed after the first year of treatment, which had
      remained stable and within normal values, thereafter until now. No abnormalities
      in bone scintigraphy were detected in the follow-up. Vitamin D unresponsive
      hypoparathyroidism maybe safely and effectively controlled at long term by s. c.
      multipulse pump treatment recombinant human PTH.

PMID- 22473759
TI  - Optical sensor enabled rocking T-flasks as novel upstream bioprocessing tools.
AB  - During the past decade, novel disposable cell culture vessels (generally referred
      to as Process Scouting Devices or PSDs) have become increasingly popular for
      laboratory scale studies and seed culture generation. However, the lack of
      engineering characterization and online monitoring tools for PSDs makes it
      difficult to elucidate their oxygen transfer capabilities. In this study, a mass
      transfer characterization (k(L)a) of sensor enabled static and rocking T-flasks
      is presented and compared with other non-instrumented PSDs such as CultiFlask
      50(r), spinner flasks, and SuperSpinner D 1000(r). We have also developed a mass
      transfer empirical correlation that accounts for the contribution of convection
      and diffusion to the volumetric mass transfer coefficient (k(L)a) in rocking T
      flasks. We also carried out a scale-down study at matched k(L) a between a
      rocking T75-flask and a 10 L (2 L filling volume) wave bioreactor (Cultibag(r))
      and we observed similar DO and pH profiles as well as maximum cell density and
      protein titer. However, in this scale-down study, we also observed a negative
      correlation between cell growth and protein productivity between the rocking T
      flask and the wave bioreactor. We hypothesize that this negative correlation can
      be due to hydrodynamic stress difference between the rocking T-flask and the
      Cultibag. As both cell culture devices share key similarities such as type of
      agitation (i.e., rocking), oxygen transfer capabilities (i.e., k(L)a) and
      disposability, we argue that rocking T-flasks can be readily integrated with wave
      bioreactors, making the transition from research-scale to manufacturing-scale a
      seamless process.

PMID- 22473761
TI  - Cigarette smoking and risk of meningioma: the effect of gender.
AB  - BACKGROUND: A number of studies have reported on the association between smoking
      and meningioma risk, with inconsistent findings. We examined the effect of gender
      on the association between cigarette smoking and risk of intracranial meningioma
      in a large population-based, case-control study. METHODS: The data include 1,433
      intracranial meningioma cases aged 29 to 79 years diagnosed among residents of
      the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay
      Area and eight Texas counties between May 1, 2006 and April 28, 2011 as well as
      1,349 controls that were frequency matched on age, sex, and geography. The data
      are analyzed separately and in a meta-analysis with six previously reported
      studies. RESULTS: Female cases who reported having ever smoked were at
      significantly decreased risk of intracranial meningioma (OR, 0.8; 95% CI, 0.7
      0.9) in contrast to male cases who were at increased risk (OR, 1.3; 95% CI, 1.0
      1.7). Similar findings were noted for current and past smokers. Smoking-induced
      risk for females did not vary by menopausal status. For males, increased duration
      of use (P = 0.04) as well as increasing number of pack-years (P = 0.02) was
      associated with elevated risk. A meta-analysis including 2,614 cases and
      1,179,686 controls resulted in an OR for ever smoking of 0.82 (95% CI, 0.68-0.98)
      for women and 1.39 (95% CI, 1.08-1.79) for men. CONCLUSION: The association of
      cigarette smoking and meningioma case status varies significantly by gender with
      women at reduced risk and men at greater risk. IMPACT: Whether the observed
      differences are associated with a hormonal etiology will require additional
      investigation.

PMID- 22473760
TI  - Cassette series designed for live-cell imaging of proteins and high-resolution
      techniques in yeast.
AB  - During the past decade, it has become clear that protein function and regulation
      are highly dependent upon intracellular localization. Although fluorescent
      protein variants are ubiquitously used to monitor protein dynamics, localization
      and abundance; fluorescent light microscopy techniques often lack the resolution
      to explore protein heterogeneity and cellular ultrastructure. Several approaches
      have been developed to identify, characterize and monitor the spatial
      localization of proteins and complexes at the suborganelle level, yet many of
      these techniques have not been applied to yeast. Thus, we have constructed a
      series of cassettes containing codon-optimized epitope tags, fluorescent protein
      variants that cover the full spectrum of visible light, a TetCys motif used for
      fluorescein arsenical hairpin (FlAsH)-based localization, and the first
      evaluation in yeast of a photoswitchable variant, mEos2, to monitor discrete
      subpopulations of proteins via confocal microscopy. This series of modules,
      complete with six different selection markers, provides the optimal flexibility
      during live-cell imaging and multicolour labelling in vivo. Furthermore, high
      resolution imaging techniques include the yeast-enhanced TetCys motif, which is
      compatible with diaminobenzidine photo-oxidation used for protein localization by
      electron microscopy, and mEos2, which is ideal for super-resolution microscopy.
      We have examined the utility of our cassettes by analysing all probes fused to
      the C-terminus of Sec61, a polytopic membrane protein of the endoplasmic
      reticulum of moderate protein concentration, in order to directly compare
      fluorescent probes, their utility and technical applications. Our series of
      cassettes expand the repertoire of molecular tools available to advance targeted
      spatiotemporal investigations using multiple live-cell, super-resolution or
      electron microscopy imaging techniques.

PMID- 22473762
TI  - Interpersonal psychotherapy for postpartum depression.
AB  - Perinatal depression is prevalent and has a great impact on both mother and
      infant. There are empirically validated treatments for both postpartum depression
      and depression during pregnancy. Primary among these is Interpersonal
      Psychotherapy, which has been shown to be effective for postpartum women across
      the spectrum from mild to severe depression. At present, Interpersonal
      Psychotherapy is the best validated treatment for postpartum depression and
      should be considered first-line treatment, especially for depressed breastfeeding
      women.

PMID- 22473763
TI  - Interpersonal psychotherapy in child and adolescent mental health services.
AB  - Over the past two decades, Interpersonal Psychotherapy (IPT) has shown itself to
      be one of only two evidence-based psychotherapies for the treatment of depression
      in adolescence-an age group where the prescribing of antidepressant medication is
      limited and where morbidity and recurrence are high. We review the literature on
      the development and research studies of the IPT model for depressed adolescent
      patients, as well as recent developments expanding its use to other cultures and
      different diagnostic areas. An overview is provided of the model in action, using
      a fictionalized case vignette. Finally, we consider the future of IPT for the
      treatment and prevention of affective disorders in the under 18 age group and in
      the context of other generations in vulnerable families.

PMID- 22473764
TI  - A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer
      chemotherapy response and prognosis.
AB  - ATP-binding cassette (ABC) transporter expression and genetic heterogeneity have
      been implicated in response to anticancer therapy. This study characterized
      genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2
      (BCRP) genes, which are key players in the metabolism of many chemotherapeutic
      agents including those used in the treatment of lung cancer. We genotyped 53
      polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small
      cell lung carcinoma (SCLC) and 206 cases of non-small cell lung carcinoma
      (NSCLC), and studied their impact on early response to chemotherapy, progression
      free survival and overall survival. SNP rs717620 in ABCC2 was moderately
      associated with a poor response to chemotherapy but strongly with shorter
      progression-free survival and overall survival in SCLC but not NSCLC patients,
      indicating that ABCC2 genetic variation is an important factor in SCLC survival
      after chemotherapy.

PMID- 22473765
TI  - Synthesis, structure, spectroscopic, and electrochemical properties of highly
      fluorescent phosphorus(V)-meso-triarylcorroles.
AB  - The synthesis, spectroscopic, and electrochemical properties of seven new P(V)
      meso-triarylcorroles (1-7) are reported. Compounds 1-7 were prepared by heating
      the corresponding free-base corroles with POCl(3) at reflux in pyridine.
      Hexacoordinate P(V) complexes of meso-triarylcorroles were isolated that
      contained two axial hydroxy groups, unlike the P(V) complex of 8,12-diethyl
      2,3,7,13,17,18-hexamethylcorrole, which was pentacoordinate, or the P(V) complex
      of meso-tetraphenylporphyrin, which was hexacoordinate with two axial chloro
      groups. (1)H and (31)P NMR spectroscopy in CDCl(3) indicated that the
      hexacoordinated P(V)-meso-triarylcorroles were prone to axial-ligand dissociation
      to form pentacoordinated P(V)-meso-triarylcorroles. However, in the presence of
      strongly coordinating solvents, such as CH(3)OH, THF, and DMSO, the P(V)-meso
      triarylcorroles preferred to exist in a hexacoordinated geometry in which the
      corresponding solvent molecules acted as axial ligands. X-ray diffraction of two
      complexes confirmed the hexacoordination environment for P(V)-meso
      triarylcorroles. Their absorption spectra in two coordinating solvents revealed
      that P(V)-meso-triarylcorroles showed a strong band at about 600 nm together with
      other bands, in contrast to P(V)-porphyrins, which showed weak bands in the
      visible region. These compounds were easier to oxidize and more difficult to
      reduce compared to P(V)-porphyrins. These compounds were brightly fluorescent,
      unlike the weakly fluorescent P(V)-porphyrins, and the quantum yields for
      selected P(V)-corroles were as high as Al(III) and Ga(III) corroles, which are
      the best known fluorescent compounds among oligopyrrolic macrocycles.

PMID- 22473766
TI  - Increased interaction between PACT molecules in response to stress signals is
      required for PKR activation.
AB  - PKR (protein kinase, RNA activated) is an interferon (IFN)-induced serine
      threonine protein kinase and is one of the key mediators in IFN's cellular
      actions. Although double-stranded (ds) RNA is the most relevant PKR activator
      during viral infections, PACT acts as a stress-modulated activator of PKR and is
      an important regulator of PKR dependent signaling pathways in the absence of
      viral infections. Stress-induced phosphorylation of PACT is essential for PACT's
      association with PKR leading to PKR activation. PKR activation by PACT leads to
      phosphorylation of translation initiation factor eIF2alpha, inhibition of protein
      synthesis, and apoptosis. In the present study, we have investigated the
      functional significance of PACT-PACT interaction in mediating PKR activation in
      response to cellular stress. Our results suggest that enhanced interaction
      between PACT molecules when PACT is phosphorylated in response to stress signals
      on serines 246 and 287 is essential for efficient PKR activation. Using a point
      mutant of PACT that is deficient in PACT-PACT interaction, we demonstrate that
      PACT-PACT interaction is essential for efficient PKR activation.

PMID- 22473767
TI  - Translational research in neurology: dementia.
AB  - Dementia disorders are characterized by clinicopathological criteria. Molecular
      understandings of these disorders, based on immunohistochemical studies,
      biochemical investigations, genetic approaches, and animal models, have resulted
      in advances in diagnosis. Likewise, translational research has allowed us to
      apply our increasing basic scientific knowledge of neurodegeneration to the
      rational development of new investigational therapies based on our current
      understanding of disease pathogenesis. This review discusses the application of
      translational research to both diagnosis and treatment of dementia disorders. The
      development of biomarkers has yielded imaging and biochemical methods that assist
      the physician more than ever in the diagnosis of neurodegenerative dementias,
      especially Alzheimer disease. New diagnostic criteria for disease are based on
      these molecular-based techniques. And these biomarkers are of potential use in
      monitoring disease activity during therapeutic trials. Translational
      investigations likewise have led toward new avenues in targeted dementia
      research. This is particularly so in the development and testing of disease
      modifying treatments that might slow or deter progressive deterioration. Recent
      clinical trials have not been based on empirical trials of established drugs but,
      rather, on trials of drugs shown, through experiments in biochemical, cell
      culture, and animal models, to interfere with known elements of the pathogenetic
      cascade of Alzheimer disease.

PMID- 22473768
TI  - Beneficial prenatal levodopa therapy in autosomal recessive guanosine
      triphosphate cyclohydrolase 1 deficiency.
AB  - OBJECTIVE: To report the first prenatal dopaminergic replacement therapy in
      autosomal recessive (AR) guanosine triphosphate cyclohydrolase 1 (GTPCH)
      deficiency without hyperphenylalaninemia. DESIGN: Case reports, literature
      review, and video presentation. SETTING: University of Lubeck, Lubeck, Germany.
      PATIENTS: Two boys from a consanguineous family. MAIN OUTCOME MEASURES: Physical
      and mental development as a function of replacement initiation. RESULTS: The
      older sibling presented with typical features of AR GTPCH deficiency due to a
      homozygous mutation in the GCH1 gene with proven pathogenicity. Levodopa
      treatment was initiated at age 10 months and resulted in a distinct motor
      improvement. However, mental development was delayed. In the younger sibling,
      prenatal replacement therapy was initiated after a prenatal diagnosis of AR GTPCH
      deficiency was made. At age 17 months, both motor and mental development were
      normal for his age. CONCLUSIONS: This report highlights the importance of an
      early diagnosis, including prenatal diagnosis, of complex dopa-responsive
      extrapyramidal syndromes. Prenatally initiated dopaminergic replacement therapy
      is beneficial and thus justified in AR GTPCH deficiency, allowing prevention of
      significant impairment of mental abilities.

PMID- 22473770
TI  - Painful tonic spasm in neuromyelitis optica: incidence, diagnostic utility, and
      clinical characteristics.
AB  - OBJECTIVES: To evaluate the diagnostic utility and clinical characteristics of
      painful tonic spasm (PTS) in neuromyelitis optica (NMO). DESIGN: Retrospective
      study. SETTING: Two referral hospitals. PATIENTS: Forty patients who had NMO
      spectrum disorder with anti-aquaporin 4 autoantibody or met the revised
      diagnostic criteria for definite NMO; 35 patients with multiple sclerosis; and 41
      patients with idiopathic acute transverse myelitis without anti-aquaporin 4
      antibody. MAIN OUTCOME MEASURES: The incidence and clinical characteristics of
      PTS in the different groups, diagnostic value of PTS in identifying patients with
      NMO, and predictors of PTS in NMO. RESULTS: The incidence of PTS was
      significantly higher in the patients with NMO (10 patients [25.0%]) than in those
      with multiple sclerosis (1 patient [2.9%]) or idiopathic acute transverse
      myelitis without anti-aquaporin 4 antibody (1 patient [2.4%]). Most PTS episodes
      (in 8 of 10 patients [80.0%]) in the NMO group occurred after a mean interval of
      48.13 days from the onset of the first myelitis episode and were not accompanied
      by another demyelinating episode with its onset. Painful tonic spasm associated
      with myelitis had a specificity of 98.7% for identifying the NMO group. Myelitis
      at disease onset was a predictor of PTS in the NMO group (odds ratio = 6.545,
      presence vs absence). CONCLUSIONS: Painful tonic spasm is a common symptom in
      NMO. When associated with myelitis, it is relatively specific to patients with
      NMO and is most commonly observed during recovery from the first myelitis
      episode. Patients with NMO presenting with myelitis at disease onset appear to be
      at higher risk for developing PTS compared with other patients with NMO.

PMID- 22473771
TI  - Diversity matters: the importance of comparative studies and the potential for
      synergy between neuroscience and evolutionary biology.
AB  - Basic research in neuroscience and clinical research on neurological disorders
      synergistically increase our understanding of the human brain. Traditionally,
      functional and clinical studies of the human brain were limited to postmortem
      histology, "natural experiments" (eg, lesions to brain areas caused by trauma or
      disease), and crude measures of electrical activity such as
      electroencephalography. More recently, the development of transcranial magnetic
      stimulation and rapid advances in imaging technology have greatly facilitated
      human brain research. In rare cases in which treating a neurological disorder
      involves implanting electrodes, researchers can even record the electrical
      activity of individual neurons. Although these approaches have led to important
      insights, they do not allow for a precise dissection of the underlying mechanisms
      by which the brain mediates perception, cognition, and behavior. Thus,
      neuroscientists and neurologists remain severely limited in the types of
      experiments they can perform on human subjects and much of our understanding of
      brain structure and function is based on research in animal models. In this
      article, I highlight the enormous potential for synergy between neuroscience and
      evolutionary biology. Nervous systems have been shaped by evolution, and
      comparative approaches take advantage of the resulting diversity to gain insight
      into the neural mechanisms of behavior. On the other hand, nervous systems and
      the behaviors and perceptions they mediate can play a fundamental role in the
      evolutionary processes that generate this diversity. To emphasize these points, I
      describe recent findings from research on African fishes that use electricity to
      communicate and navigate in their dark underwater world.

PMID- 22473772
TI  - Development and preliminary validation of the Parent Efficacy for Child Healthy
      Weight Behaviour Scale.
AB  - This study developed a new measure of parent self-efficacy for promoting healthy
      weight behaviours in their children, the Parent Efficacy for Child Healthy Weight
      Behaviour Scale (PECHWB). In total 601 primary caregivers of children aged 4-17
      completed an online survey consisting of the PECHWB, a measure of general
      parenting self-efficacy, measures of parental depression, anxiety and stress and
      demographic questions. Factor analysis identified four PECHWB subscales with high
      levels of internal consistency. The PECHWB showed significant small positive
      correlations with a measure of global parenting self-efficacy and small negative
      correlations with measures of parental negative affect. This study provides
      initial evidence for the reliability and validity of the PECHWB. Future research
      is required to establish further evidence of the psychometric properties of the
      PECHWB scale in independent samples before the scale can be used in evaluating
      intervention outcomes.

PMID- 22473769
TI  - Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels
      in patients with mild to moderate Alzheimer disease.
AB  - BACKGROUND: Given the slow and variable clinical course of Alzheimer disease,
      very large and extended clinical trials are needed to identify a beneficial
      clinical effect of disease-modifying treatments. Therefore, biomarkers are
      essential to prove that an anti-beta-amyloid (Abeta) drug candidate affects both
      Abeta metabolism and plaque load as well as downstream pathogenic mechanisms.
      OBJECTIVE: To evaluate the effect of the anti-Abeta monoclonal antibody
      bapineuzumab on cerebrospinal fluid (CSF) biomarkers reflecting Abeta
      homeostasis, neuronal degeneration, and tau-related pathology in patients with
      Alzheimer disease. DESIGN: Two phase 2, multicenter, randomized, double-blind,
      placebo-controlled clinical trials of 12-month duration. SETTING: Academic
      centers in the United States (Study 201) and England and Finland (Study 202).
      PATIENTS: Forty-six patients with mild to moderate Alzheimer disease.
      INTERVENTIONS: Patients received either placebo (n = 19) or bapineuzumab (n = 27)
      in 3 or 4 ascending dose groups. MAIN OUTCOME MEASURES: Changes between end of
      study and baseline in the exploratory CSF biomarkers Abeta1-42, AbetaX-42, AbetaX
      40; total tau (T-tau); and phosphorylated tau (P-tau). RESULTS: Within the
      bapineuzumab group, a decrease at end of study compared with baseline was found
      both for CSF T-tau (-72.3 pg/mL) and P-tau (-9.9 pg/mL). When comparing the
      treatment and placebo groups, this difference was statistically significant for P
      tau (P = .03), while a similar trend for a decrease was found for T-tau (P =
      .09). No clear-cut differences were observed for CSF Abeta. CONCLUSIONS: To our
      knowledge, this study is the first to show that passive Abeta immunotherapy with
      bapineuzumab results in decreases in CSF T-tau and P-tau, which may indicate
      downstream effects on the degenerative process. Cerebrospinal fluid biomarkers
      may be useful to monitor the effects of novel disease-modifying anti-Abeta drugs
      in clinical trials. TRIAL REGISTRATIONS clinicaltrials.gov Identifier:
      NCT00112073, EudraCT Identifier: 2004-004120-12, and isrctn.org Identifier:
      ISRCTN17517446.

PMID- 22473773
TI  - Nanog regulates self-renewal of cancer stem cells through the insulin-like growth
      factor pathway in human hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) exhibits cellular heterogeneity and embryonic stem
      cell-related genes are preferentially overexpressed in a fraction of cancer cells
      of poorly differentiated tumors. However, it is not known whether or how these
      cancer cells contribute to tumor initiation and progression. Here, our data
      showed that increased expression of pluripotency transcription factor Nanog in
      cancer cells correlates with a worse clinical outcome in HCC. Using the Nanog
      promoter as a reporter system, we could successfully isolate a small
      subpopulation of Nanog-positive cells. We demonstrate that Nanog-positive cells
      exhibited enhanced ability of self-renewal, clonogenicity, and initiation of
      tumors, which are consistent with crucial hallmarks in the definition of cancer
      stem cells (CSCs). Nanog(Pos) CSCs could differentiate into mature cancer cells
      in in vitro and in vivo conditions. In addition, we found that Nanog(Pos) CSCs
      exhibited resistance to therapeutic agents (e.g., sorafenib and cisplatin) and
      have a high capacity for tumor invasion and metastasis. Knock-down expression of
      Nanog in Nanog(Pos) CSCs could decrease self-renewal accompanied with decreased
      expression of stem-cell-related genes and increased expression of mature
      hepatocyte-related genes. Overexpression of Nanog in Nanog(Neg) cells could
      restore self-renewal. Furthermore, we found that insulin-like growth factor
      (IGF)2 and IGF receptor (IGF1R) were up-regulated in Nanog(Pos) CSCs. Knock-down
      expression of Nanog in Nanog(Pos) CSCs inhibited the expression of IGF1R, and
      overexpression of Nanog in Nanog(Neg) cells increased the expression of IGF1R. A
      specific inhibitor of IGF1R signaling could significantly inhibit self-renewal
      and Nanog expression, indicating that IGF1R signaling participated in Nanog
      mediated self-renewal. CONCLUSION: These data indicate that Nanog could be a
      novel biomarker for CSCs in HCC, and that Nanog could play a crucial role in
      maintaining the self-renewal of CSCs through the IGF1R-signaling pathway.

PMID- 22473774
TI  - Organocatalytic asymmetric synthesis of trifluoromethyl-substituted
      diarylpyrrolines: enantioselective conjugate cyanation of beta-aryl-beta
      trifluoromethyl-disubstituted enones.
AB  - Ether way: the cinchona-alkaloid-catalyzed title reaction was achieved in high
      yields with high to excellent ee values for the first time, and affords key
      intermediates for the biologically important 2 having a trifluoromethylated all
      carbon quaternary chiral center. Ether-type catalysts (1) are more efficient in
      this transformation than the conventional hydroxy analogues.

PMID- 22473775
TI  - Activation of peroxisome proliferator-activated receptor-delta attenuates
      glutamate-induced neurotoxicity in HT22 mouse hippocampal cells.
AB  - Glutamate-induced neurotoxicity has been implicated in the pathogenesis of
      neurodegenerative disorders; however, little is known about the cellular events
      that underlie neurotoxicity or how to impede these events. This study
      demonstrates that peroxisome proliferator-activated receptor (PPAR)-delta
      regulates glutamate-induced neurotoxicity in HT22 mouse hippocampal cells.
      Activation of PPARdelta by GW501516, a specific ligand, significantly inhibited
      glutamate-induced cell death and reactive oxygen species (ROS) production in HT22
      cells. The siRNA-mediated knockdown of PPARdelta abrogated the effects of
      GW501516 in neuronal toxicity and ROS production induced by glutamate. In
      addition, ligand-activated PPARdelta reduced the glutamate-induced level of
      intracellular calcium ions (Ca(2+)) by modulating the influx of Ca(2+) from the
      extracellular space. Similarly, glutamate-induced cell death and intracellular
      Ca(2+) levels were attenuated in the presence of LY83583, an inhibitor of soluble
      guanylyl cyclase. Taken together, these results suggest that PPARdelta plays an
      important role in glutamate-induced neurotoxicity by modulating oxidative stress
      and Ca(2+) influx.

PMID- 22473776
TI  - The omega-6 fatty acid derivative 15-deoxy-Delta12,14-prostaglandin J2 is
      involved in neuroprotection by enteric glial cells against oxidative stress.
AB  - Increasing evidence suggests that enteric glial cells (EGCs) are critical for
      enteric neuron survival and functions. In particular, EGCs exert direct
      neuroprotective effects mediated in part by the release of glutathione. However,
      other glial factors such as those identified as regulating the intestinal
      epithelial barrier and in particular the omega-6 fatty acid derivative 15-deoxy
      Delta12,14-prostaglandin J2 (15d-PGJ2) could also be involved in EGC-mediated
      neuroprotection. Therefore, our study aimed to assess the putative role of EGC
      derived 15d-PGJ2 in their neuroprotective effects. We first showed that
      pretreatment of primary cultures of enteric nervous system(ENS)or humann
      euroblastoma cells (SH-SY5Y)with 15d-PGJ2 dose dependently prevented hydrogen
      peroxide neurotoxicity. Furthermore, neuroprotective effects of EGCs were
      significantly inhibited following genetic invalidation in EGCs of the key enzyme
      involved in 15d-PGJ2 synthesis, i.e. L-PGDS. We next showed that 15d-PGJ2 effects
      were mediated by an Nrf2 dependent pathway but were not blocked by PPARgamma
      inhibitor (GW9662) in SH-SY5Y cells and enteric neurons. Finally, 15d-PGJ2
      induced a significant increase in glutamate cysteine ligase expression and
      intracellular glutathione in SH cells and enteric neurons. In conclusion, we
      identified 15d-PGJ2 as a novel glial-derived molecule with neuroprotective
      effects in the ENS. This study further supports the concept that omega-6
      derivatives such as 15d-PGJ2 might be used in preventive and/or therapeutic
      strategies for the treatment of enteric neuropathies.

PMID- 22473777
TI  - Human spermatozoa possess a calcium-dependent chloride channel that may
      participate in the acrosomal reaction.
AB  - Motility, maturation and the acrosome reaction (AR) are fundamental functions of
      mammalian spermatozoa. While travelling through the female reproductive tract,
      spermatozoa must mature through a process named capacitation, so that they can
      reach the egg and undergo the AR, an exocytotic event necessary to fertilize the
      egg. Though Cl- is important for sperm capacitation and for the AR, not much is
      known about the molecular identity of the Cl- transporters involved in these
      processes.We implemented a modified perforated patch-clamp strategy to obtain
      whole cell recordings sealing on the head of mature human spermatozoa.Our whole
      cell recordings revealed the presence of a Ca2+-dependent Cl- current. The
      biophysical characteristics of this current and its sensitivity to niflumic acid
      (NFA) and 4,4-diisothiocyano-2,2-stilbene disulphonic acid (DIDIS) are consistent
      with those displayed by the Ca2+-dependent Cl- channel from the anoctamin family
      (TMEM16). Whole cell patch clamp recordings in the cytoplasmic droplet of human
      spermatozoa corroborated the presence of these currents, which were sensitive to
      NFA and to a small molecule TMEM16A inhibitor (TMEM16Ainh, an
      aminophenylthiazole). Importantly, the human sperm AR induced by a recombinant
      human glycoprotein from the zona pellucida, rhZP3, displayed a similar
      sensitivity to NFA, DIDS and TMEM16Ainh as the sperm Ca2+-dependent Cl- currents.
      Our findings indicate the presence of Ca2+-dependent Cl- currents in human
      spermatozoa, that TMEM16A may contribute to these currents and also that sperm
      Ca2+-dependent Cl- currents may participate in the rhZP3-induced AR.

PMID- 22473778
TI  - The chemokine CXCL12 and the HIV-1 envelope protein gp120 regulate spontaneous
      activity of Cajal-Retzius cells in opposite directions.
AB  - Activation of the CXC chemokine receptor 4 (CXCR4) in Cajal-Retzius cells by CXC
      chemokine ligand 12 (CXCL12) is important for controlling their excitability.
      CXCR4 is also a co-receptor for the glycoprotein 120 (gp120) of the envelope of
      the human immunodeficiency virus type 1 (HIV-1), and binding of gp120 to CXCR4
      may produce pathological effects. In order to study CXCR4-dependent modulation of
      membrane excitability, we recorded in cell-attached configuration spontaneous
      action currents from hippocampal stratum lacunosum-moleculare Cajal-Retzius cells
      of the CXCR4-EGFP mouse. CXCL12 (50 nM) powerfully inhibited firing independently
      of synaptic transmission, suggesting that CXCR4 regulates an intrinsic
      conductance. This effect was prevented by conditioning slices with BAPTA-AM (200
      MUM), and by blockers of the BK calcium-dependent potassium channels (TEA (1 mM),
      paxilline (10 MUM) and iberiotoxin (100 nM)). In contrast, exposure to gp120
      (pico- to nanomolar range, alone or in combination with soluble cluster of
      differentiation 4 (CD4)), enhanced spontaneous firing frequency. This effect was
      prevented by the CXCR4 antagonist AMD3100 (1 MUM) and was absent in EGFP-negative
      stratum lacunosum-moleculare interneurons. Increased excitability was prevented
      by treating slices with BAPTA-AM or bumetanide, suggesting that gp120 activates a
      mechanism that is both calcium- and chloride-dependent. In conclusion, our
      results demonstrate that CXCL12 and gp120 modulate the excitability of Cajal
      Retzius cells in opposite directions. We propose that CXCL12 and gp120 either
      generate calcium responses of different strength or activate distinct pools of
      intracellular calcium, leading to agonist-specific responses, mediated by BK
      channels in the case of CXCL12, and by a chloride-dependent mechanism in the case
      of gp120.

PMID- 22473780
TI  - Cerebellar modulation of human associative plasticity.
AB  - Paired associative stimulation (PAS) is a method commonly used in human studies
      of motor cortex synaptic plasticity. It involves repeated pairs of electrical
      stimuli to the median nerve and transcranial magnetic stimulation (TMS) of the
      motor cortex. If the interval between peripheral and TMS stimulation is around 21
      25 ms, corticospinal excitability is increased for the following 30-60 min via a
      long term potentiation (LTP)-like effect within the primary motor cortex.
      Previous work has shown that PAS depends on the present and previous levels of
      activity in cortex, and that it can be modified by motor learning or attention.
      Here we show that simultaneous transcranial direct current stimulation (TDCS; 2
      mA) over the cerebellum can abolish the PAS effect entirely. Surprisingly, the
      effect is seen when the PAS interval is 25 ms but not when it is 21.5 ms. There
      are two implications from this work. First, the cerebellum influences PAS effects
      in motor cortex; second, LTP-like effects of PAS have at least two different
      mechanisms. The results are relevant for interpretation of pathological changes
      that have been reported in response to PAS in people with movement disorders and
      to changes in healthy individuals following exercise or other interventions.

PMID- 22473779
TI  - How the Hodgkin-Huxley equations inspired the Cardiac Physiome Project.
AB  - Early modelling of cardiac cells (1960-1980) was based on extensions of the
      Hodgkin-Huxley nerve axon equations with additional channels incorporated, but
      after 1980 it became clear that processes other than ion channel gating were also
      critical in generating electrical activity. This article reviews the development
      of models representing almost all cell types in the heart, many different
      species, and the software tools that have been created to facilitate the cardiac
      Physiome Project.

PMID- 22473781
TI  - Improvements in skeletal muscle strength and cardiac function induced by
      resveratrol during exercise training contribute to enhanced exercise performance
      in rats.
AB  - Exercise training (ET) improves endurance capacity by increasing both skeletal
      muscle mitochondrial number and function, as well as contributing to favourable
      cardiac remodelling.Interestingly, some of the benefits of regular exercise can
      also be mimicked by the naturally occurring polyphenol, resveratrol (RESV).
      However, it is not known whether RESV enhances physiological adaptations to ET.
      To investigate this, male Wistar rats were randomly assigned to a control chow
      diet or a chow diet that contained RESV (4 g kg-1 of diet) and subsequently
      subjected to a programme of progressive treadmill running for 12 weeks. ET
      induced improvements in exercise performance were enhanced by 21% (P <0.001) by
      the addition of RESV to the diet. In soleus muscle, ET+RESV increased both the
      twitch (1.8-fold; P <0.05) and tetanic(1.2-fold; P <0.05) forces generated during
      isometric contraction, compared to ET alone. In vivo echocardiography
      demonstrated that ET+RESV also increased the resting left ventricular ejection
      fraction by 10% (P <0.05), and reduced left ventricular wall stress compared to
      ET alone.These functional changes were accompanied by increased cardiac fatty
      acid oxidation (1.2-fold;P <0.05) and favourable changes in cardiac gene
      expression and signal transduction pathways that optimized the utilization of
      fatty acids in ET+RESV compared to ET alone. Overall, our findings provide
      evidence that the capacity for fatty acid oxidation is augmented by the addition
      of RESV to the diet during ET, and that this may contribute to the improved
      physical performance of rats following ET.

PMID- 22473782
TI  - Modulation of synaptic input by GABAB receptors improves coincidence detection
      for computation of sound location.
AB  - Interaural time disparities (ITDs) are the primary cues for localisation of low
      frequency sound stimuli. ITDs are computed by coincidence-detecting neurones in
      the medial superior olive (MSO) in mammals. Several previous studies suggest that
      control of synaptic gain is essential for maintaining ITD selectivity as stimulus
      intensity increases. Using acute brain slices from postnatal day 7 to 24 (P7-P24)
      Mongolian gerbils, we confirm that activation of GABAB receptors reduces the
      amplitude of excitatory and inhibitory synaptic currents to the MSO and,
      moreover, show that the decay kinetics of IPSCs are slowed in mature animals.
      During repetitive stimuli, activation of GABAB receptors reduced the amount of
      depression observed, while PSC suppression and the slowed kinetics were
      maintained. Additionally, we used physiological and modelling approaches to test
      the potential impact of GABAB activation on ITD encoding in MSO neurones. Current
      clamp recordings from MSO neurones were made while pharmacologically isolated
      excitatory inputs were bilaterally stimulated using pulse trains that simulate
      ITDs in vitro. MSO neurones showed strong selectivity for bilateral delays.
      Application of both GABAB agonists and antagonists demonstrate that GABAB
      modulation of synaptic input can sharpen ITD selectivity. We confirmed and
      extended these results in a computational model that allowed for independent
      manipulation of each GABAB-dependent effect. Modelling suggests that modulation
      of both amplitude and kinetics of synaptic inputs by GABAB receptors can improve
      precision of ITD computation. Our studies suggest that in vivo modulation of
      synaptic input by GABAB receptors may act to preserve ITD selectivity across
      various stimulus conditions.

PMID- 22473783
TI  - Voltage-gated sodium channels at 60: structure, function and pathophysiology.
AB  - Voltage-gated sodium channels initiate action potentials in nerve, muscle and
      other excitable cells. The sodium current that initiates the nerve action
      potential was discovered by Hodgkin and Huxley using the voltage clamp technique
      in their landmark series of papers in The Journal of Physiology in 1952. They
      described sodium selectivity, voltage-dependent activation and fast inactivation,
      and they developed a quantitative model for action potential generation that has
      endured for many decades. This article gives an overview of the legacy that has
      evolved from their work, including development of conceptual models of sodium
      channel function, discovery of the sodium channel protein, analysis of its
      structure and function, determination of its structure at high resolution,
      definition of the mechanism and structural basis for drug block, and exploration
      of the role of the sodium channel as a target for disease mutations. Structural
      models for sodium selectivity and conductance, voltage-dependent activation, fast
      inactivation and drug block are discussed. A perspective for the future envisions
      new advances in understanding the structural basis for sodium channel function,
      the role of sodium channels in disease and the opportunity for discovery of novel
      therapeutics.

PMID- 22473784
TI  - 'Metabolic syndrome' in the brain: deficiency in omega-3 fatty acid exacerbates
      dysfunctions in insulin receptor signalling and cognition.
AB  - We pursued studies to determine the effects of the metabolic syndrome (MetS) on
      brain, and the possibility of modulating these effects by dietary interventions.
      In addition, we have assessed potential mechanisms by which brain metabolic
      disorders can impact synaptic plasticity and cognition. We report that high
      dietary fructose consumption leads to an increase in insulin resistance index,
      and insulin and triglyceride levels, which characterize MetS. Rats fed on an n-3
      deficient diet showed memory deficits in a Barnes maze, which were further
      exacerbated by fructose intake. In turn, an n-3 deficient diet and fructose
      interventions disrupted insulin receptor signalling in hippocampus as evidenced
      by a decrease in phosphorylation of the insulin receptor and its downstream
      effector Akt. We found that high fructose consumption with an n-3 deficient diet
      disrupts membrane homeostasis as evidenced by an increase in the ratio of n-6/n-3
      fatty acids and levels of 4-hydroxynonenal, a marker of lipid peroxidation.
      Disturbances in brain energy metabolism due to n-3 deficiency and fructose
      treatments were evidenced by a significant decrease in AMPK phosphorylation and
      its upstream modulator LKB1 as well as a decrease in Sir2 levels. The decrease in
      phosphorylation of CREB, synapsin I and synaptophysin levels by n-3 deficiency
      and fructose shows the impact of metabolic dysfunction on synaptic plasticity.
      All parameters of metabolic dysfunction related to the fructose treatment were
      ameliorated by the presence of dietary n-3 fatty acid. Results showed that
      dietary n-3 fatty acid deficiency elevates the vulnerability to metabolic
      dysfunction and impaired cognitive functions by modulating insulin receptor
      signalling and synaptic plasticity.

PMID- 22473785
TI  - Supraspinal fatigue after normoxic and hypoxic exercise in humans.
AB  - Inadequate cerebral O2 availability has been proposed to be an important
      contributing factor to the development of central fatigue during strenuous
      exercise. Here we tested the hypothesis that supraspinal processes of fatigue
      would be increased after locomotor exercise in acute hypoxia compared to
      normoxia, and that such change would be related to reductions in cerebral O2
      delivery and tissue oxygenation. Nine endurance-trained cyclists completed three
      constant-load cycling exercise trials at ~80% of maximal work rate: (1) to the
      limit of tolerance in acute hypoxia; (2) for the same duration but in normoxia
      (control); and (3) to the limit of tolerance in normoxia. Throughout each trial,
      prefrontal cortex tissue oxygenation and middle cerebral artery blood velocity
      (MCAV) were assessed using near-infrared spectroscopy and trans-cranial Doppler
      sonography, respectively. Cerebral O2 delivery was calculated as the product of
      arterial O2 content and MCAV. Before and immediately after each trial, twitch
      responses to supramaximal femoral nerve stimulation and transcranial magnetic
      stimulation were obtained to assess neuromuscular and cortical function,
      respectively. Exercise time was reduced by 54%in hypoxia compared to normoxia
      (3.6 +/- 1.3 vs. 8.1 +/- 2.9 min; P<0.001). Cerebral O2 delivery,cerebral
      oxygenation and maximum O2 uptake were reduced whereas muscle electromyographic
      activity was increased in hypoxia compared to control (P <0.05).Maximum voluntary
      force and potentiated quadriceps twitch force were decreased below baseline after
      exercise in each trial;the decreases were greater in hypoxia compared to control
      (P<0.001), but were not different in the exhaustive trials (P>0.05). Cortical
      voluntary activation was also decreased after exercise in all trials, but the
      decline in hypoxia (Delta18%) was greater than in the normoxic trials (Delta5
      9%)(P <0.05). The reductions in cortical voluntary activation were paralleled by
      reductions in cerebral O2 delivery. The results suggest that curtailment of
      exercise performance in acute severe hypoxia is due, in part, to failure of drive
      from the motor cortex, possibly as a consequence of diminished O2 availability in
      the brain.

PMID- 22473786
TI  - The effect of fresh bone marrow cells on reconstruction of mouse calvarial defect
      combined with calvarial osteoprogenitor cells and collagen-apatite scaffold.
AB  - Fresh bone marrow cells have already exhibited its advantages as osteogenic donor
      cells, but the combination between fresh bone marrow cells and other donor cells
      utilized for bone healing has not been fully explored. To highlight the impact of
      fresh bone marrow cells on scaffold-based bone regeneration, single or a
      combination of calvarial osteoprogenitor cells (OPCs) and bone marrow cells
      (BMCs) were used as donor cells combined with collagen-apatite scaffold for
      calvarial defect healing. The host and donor contributions to bone formation were
      assessed using histological and GFP imaging analysis. Although the amount of new
      bone formed by different cell sources did not show significant differences, the
      origin of the bone formation in the defects mainly depended on the types of donor
      cells employed: when only calvarial OPCs were used as donor cells, a donor
      derived bone healing instead of host-derived bone ingrowth was observed; when
      only fresh BMCs were loaded, the host bone could grow into the defect along the
      lamellar structure of the scaffolds, but the amount of new bone formed was
      significantly lower than the defect loaded with calvarial OPCs only. The
      combination of calvarial OPCs and fresh BMCs had similar amount of new bone
      formation as the group loaded with calvarial osteoprogenitors alone, but did not
      induce any host-derived bone formation. These results provide compelling evidence
      of the importance of fresh BMCs to induce host-implant integration in bone tissue
      engineering.

PMID- 22473787
TI  - Multilayer reconstructions for defects overlying the Achilles tendon with the
      lateral-arm flap: long-term follow-up of 16 cases.
AB  - Defects of the Achilles tendon and the overlying soft tissue are challenging to
      reconstruct. The lateral-arm flap has our preference in this region as it
      provides thin pliable skin, in addition, the fascia and tendon can be included in
      the flap as well. The aim of this report is to share the experience the authors
      gained with this type of reconstruction. The authors report the largest series in
      the published reports today. PATIENTS AND METHODS: A retrospective review was
      performed of all patients treated between January 2000 and January 2009 with a
      lateral-arm flap for a soft-tissue defect overlying the Achilles tendon. RESULTS:
      In the reviewed period, 16 soft-tissue defects overlying the Achilles tendon were
      reconstructed, with a mean follow-up of 63 months. In three cases, tendon was
      included into the flap and in two, a sensory nerve was coapted. Fifteen cases
      (94%) were successful, one failed. In seven cases, a secondary procedure was
      necessary for thinning of the flap. CONCLUSION: The lateral-arm flap is a good
      and safe option for the reconstruction of defects overlying the Achilles tendon.

PMID- 22473788
TI  - Catching gaseous SO2 in cone-type lanthanide complexes: an unexpected
      coordination mode for SO2 in f-element chemistry.
AB  - Easy come, easy go: the first molecular SO(2) complexes of the lanthanides
      (Ln=Sm, Eu) have been prepared. The compounds can reversibly coordinate gaseous
      SO(2). Concomitant with the addition and removal of SO(2), the color of the
      complexes changes reversibly. The structures of the SO(2) compounds could be
      confirmed in solution and in the solid state.

PMID- 22473789
TI  - Androgenic and spermatogenic activity of alkylamide-rich ethanol solution extract
      of Anacyclus pyrethrum DC.
AB  - Anacyclus pyrethrum (A. pyrethrum) has been used as Vajikaran Rasayana
      (aphrodisiac) in traditional Indian ayurvedic medicine to treat male sexual
      dysfunction, including infertility. Aphrodisiac activity may be due to an
      increase in the production or effect of androgens, so this study sought to
      evaluate the androgenic and spermatogenic potential of the alkylamide-rich
      ethanol solution extract. Male Wistar strain rats weighing between 150 and 180 g
      were completely randomized divided into five groups. The ethanol solution extract
      of A. pyrethrum was administered to groups of rats in 50, 100, and 150 mg/kg
      doses for a period of 28 days, and the action was compared with control and
      testosterone-treated rats. Thirteen N-alkylamides were detected in the extract by
      using HPLC/UV/electrospray ionization mass spectrometry method. Extract
      administration at all the doses produced significant increase in body weight,
      sperm count, motility, and viability along with serum testosterone, luteinizing
      hormone, and follicle-stimulating hormone concentrations. Histoarchitecture of
      testis revealed increased spermatogenic activities. Seminal fructose content was
      also significantly increased after 28 days of treatment. Our results suggest that
      the ethanol solution extract of the roots of A. pyrethrum has androgenic
      potential and may improve male fertility by enhancing spermatogenesis.

PMID- 22473791
TI  - [Osteopenia of prematurity - a current problem?].

PMID- 22473792
TI  - Characteristics and consumption patterns of Australian organic consumers.
AB  - BACKGROUND: Increasingly, Australians are choosing to consume organically
      produced food, but only a small percentage consume organic food exclusively, and
      there is little information in the scientific literature that describes their
      actual level of intake. In order to provide a more meaningful description of
      Australian organic consumers the 'Organic Consumption Survey' and 'Organic Food
      Intake Survey' were conducted online in 2010. The aims were to provide
      information about the characteristics of regular organic consumers and quantify
      levels of organic consumption. RESULTS: The majority of participants (n = 318)
      were female (80.3%), 25-55 years old (80.3%), living in urban areas (61.2%), born
      in Australia (68.9%) and were in a healthy weight range (55.5%). Organic fruit
      and vegetables had the highest uptake by organic consumers and meat products the
      lowest. The majority of participants consumed at least 65% organic food in their
      diet, including 35% certified organic food. CONCLUSION: A better understanding of
      organic consumers may help to serve the long-term interests of the organic
      industry and other stakeholders of food marketing. Clearer definitions of organic
      consumers may also inform research evaluating the purported health benefits of
      organic foods.

PMID- 22473793
TI  - Physiological effects of free fatty acid production in genetically engineered
      Synechococcus elongatus PCC 7942.
AB  - The direct conversion of carbon dioxide into biofuels by photosynthetic
      microorganisms is a promising alternative energy solution. In this study, a model
      cyanobacterium, Synechococcus elongatus PCC 7942, is engineered to produce free
      fatty acids (FFA), potential biodiesel precursors, via gene knockout of the FFA
      recycling acyl-ACP synthetase and expression of a thioesterase for release of the
      FFA. Similar to previous efforts, the engineered strains produce and excrete FFA,
      but the yields are too low for large-scale production. While other efforts have
      applied additional metabolic engineering strategies in an attempt to boost FFA
      production, we focus on characterizing the engineered strains to identify the
      physiological effects that limit cell growth and FFA synthesis. The strains
      engineered for FFA-production show reduced photosynthetic yields, chlorophyll-a
      degradation, and changes in the cellular localization of the light-harvesting
      pigments, phycocyanin and allophycocyanin. Possible causes of these physiological
      effects are also identified. The addition of exogenous linolenic acid, a
      polyunsaturated FFA, to cultures of S. elongatus 7942 yielded a physiological
      response similar to that observed in the FFA-producing strains with only one
      notable difference. In addition, the lipid constituents of the cell and thylakoid
      membranes in the FFA-producing strains show changes in both the relative amounts
      of lipid components and the degree of saturation of the fatty acid side chains.
      These changes in lipid composition may affect membrane integrity and structure,
      the binding and diffusion of phycobilisomes, and the activity of membrane-bound
      enzymes including those involved in photosynthesis. Thus, the toxicity of
      unsaturated FFA and changes in membrane composition may be responsible for the
      physiological effects observed in FFA-producing S. elongatus 7942. These issues
      must be addressed to enable the high yields of FFA synthesis necessary for large
      scale biofuel production.

PMID- 22473794
TI  - Depression in early, middle and late adolescence: differential evidence for the
      cognitive diathesis-stress model.
AB  - Cognitive theory is a prominent framework to study depression in both adults and
      adolescents. This theory stated that dysfunctional schemas are moderators (known
      as diathesis) in the association of current stress and psychopathology. However,
      in adolescents, less evidence has been found so far to corroborate the importance
      of these schemas. This study aimed to investigate in a cross-sectional design the
      moderating role of adolescents' early maladaptive schemas (EMS) on depressive
      symptoms. This will be studied in relation to both important daily stressors
      (i.e., maternal, paternal and peer rejection) and stressful life events. METHOD:
      Adolescents (N = 228, age 12-18 years), selected from inpatient and outpatient
      clinical settings and a non-referred sample, completed questionnaires and
      interviews measuring psychopathology, cognitive schemas, peer rejection, maternal
      and paternal rejection, and stressful life events. Parents completed
      questionnaires about their adolescent measuring psychopathology, stressful life
      events and peer rejection, as well as their own parental behaviour. RESULTS:
      Correlational analyses revealed significant associations between the study
      variables. Evidence was found for an interaction effect between the adolescents'
      EMS and peer rejection in explaining depressive symptoms, but only in late
      adolescents. KEY PRACTITIONER MESSAGE: Stress induced by maternal and, in lesser
      extent, paternal rejection is contributing to depressive symptoms primarily in
      younger and to lesser extent in older age groups. The quality of peer
      relationships becomes an increasingly salient source of distress as adolescence
      unfolds and is certainly an important mechanism affecting depression in
      adolescence. Maladaptive schemas only start functioning as a cognitive diathesis
      in late adolescence, increasing depression in response to peer-related distress.
      Since maladaptive schemas are not yet operating as cognitive vulnerability
      factors in early and middle adolescence, early interventions for depressive
      disorders may be more effective compared with treatment in later adolescence.

PMID- 22473795
TI  - Simultaneous determination of lamivudine, lopinavir, ritonavir, and zidovudine
      concentration in plasma of HIV-infected patients by HPLC-MS/MS.
AB  - The nucleoside reverse transcriptase inhibitors lamivudine and zidovudine and the
      protease inhibitors lopinavir and ritonavir are currently used in anti-human
      immunodeficiency virus (HIV) therapy. Here, a high-performance liquid
      chromatography-mass spectrometry (HPLC-MS/MS) method, using a hybrid quadrupole
      time-of-flight mass analyzer, is reported for the simultaneous quantification of
      lamivudine, lopinavir, ritonavir, and zidovudine in plasma of HIV-infected
      patients. The volume of plasma sample was 600 MUL. Plasma samples were extracted
      by solid-phase using 1 cc Oasis HLB Cartridge (divinylbenzene and N
      vinylpyrrolidone) and evaporated in a water bath under nitrogen stream. The
      extracted samples were reconstituted with 100-MUL methanol. Five microliters of
      the reconstituted samples were injected into a HPLC-MS/MS apparatus, and the
      analytes were eluted on a Vydac column (250 * 1.0 mm i.d.) filled with 3-MUm
      C(18) particles. The mobile phase was delivered at 70 MUL/min with a linear
      gradient elution, both acetonitrile and ultrapure water solvents contained 0.2%
      formic acid. The calibration curves were linear from 0.47 to 20 ng/mL. The
      absolute recovery ranged between 91 and 107%. The minimal concentration of
      lamivudine, lopinavir, ritonavir, and zidovudine detectable by HPLC-MS/MS is
      0.47, 0.28, 0.30, and 0.66 ng/mL, respectively. The great advantage of the new
      HPLC-MS/MS method here reported is the possibility to achieve a very high
      specificity toward the selected anti-HIV drugs, despite the simple and rapid
      sample preparation. Moreover, this method is easily extendible to the analysis of
      co-administrated drugs.

PMID- 22473796
TI  - Nutrition in Clinical Practice. Pre- and probiotics. Editor's note.

PMID- 22473797
TI  - Probiotics in the intensive care unit.
AB  - Probiotics are living microorganisms that, when ingested in adequate amounts,
      provide benefits to the host. The benefits include either a shortened duration of
      infections or decreased susceptibility to pathogens. Proposed mechanisms of
      beneficial effects include improving gastrointestinal barrier function,
      modification of the gut flora by inducing host cell antimicrobial peptides and/or
      local release of probiotic antimicrobial factors, competition for epithelial
      adherence, and immunomodulation. With increasing intensive care unit (ICU)
      antibacterial resistance rates and fewer new antibiotics in the research
      pipeline, focus has been shifted to non-antibiotic approaches for the prevention
      and treatment of nosocomial infections. Probiotics offer promise to ICU patients
      for the prevention of antibiotic-associated diarrhea, Clostridium difficile
      infections, multiple organ dysfunction syndrome, and ventilator-associated
      pneumonia. Our current understanding of probiotics is confounded by inconsistency
      in probiotic strains studied, optimal dosages, study durations, and suboptimal
      sample sizes. Although probiotics are generally safe in the critically ill,
      adverse event monitoring must be rigorous in these vulnerable patients.
      Delineation of clinical differences of various effective probiotic strains, their
      mechanisms of action, and optimal dosing regimens will better establish the role
      of probiotics in various disorders. However, probiotic research will likely be
      hindered in the future given a recent ruling by the U.S. Food and Drug
      Administration.

PMID- 22473799
TI  - Type 1 inositol-1,4,5-trisphosphate receptor is a late substrate of caspases
      during apoptosis.
AB  - Apoptosis is characterized by the proteolytic cleavage of hundreds of proteins.
      One of them, the type 1 inositol-1,4,5-trisphosphate receptor (IP(3) R-1), a
      multimeric receptor located on the endoplasmic reticulum (ER) membrane that is
      critical to calcium homeostasis, was reported to be cleaved during staurosporine
      (STS) induced-apoptosis in Jurkat cells. Because the reported cleavage site
      separates the IP(3) binding site from the channel moiety, its cleavage would shut
      down a critical signaling pathway that is common to several cellular processes.
      Here we show that IP(3) R-1 is not cleaved in 293 cells treated with STS,
      TNFalpha, Trail, or ultra-violet (UV) irradiation. Further, it is not cleaved in
      Hela or Jurkat cells induced to undergo apoptosis with Trail, TNFalpha, or UV. In
      accordance with previous reports, we demonstrate that it is cleaved in a Jurkat
      cell line treated with STS. However its cleavage occurs only after poly(ADP
      ribose) polymerase (PARP), which cleavage is a hallmark of apoptosis, and p23, a
      poor caspase-7 substrate, are completely cleaved, suggesting that IP(3) R-1 is a
      relatively late substrate of caspases. Nevertheless, the receptor is fully
      accessible to proteolysis in cellulo by ectopically overexpressed caspase-7 or by
      the tobacco etch virus (TEV) protease. Finally, using recombinant caspase-3 and
      microsomal fractions enriched in IP(3) R-1, we show that the receptor is a poor
      caspase-3 substrate. Consequently, we conclude that IP(3) R-1 is not a key death
      substrate.

PMID- 22473800
TI  - Selective and sensitive recognition of Cu2+ in an aqueous medium: a surface
      enhanced Raman scattering (SERS)-based analysis with a low-cost Raman reporter.
AB  - In the present study, surface-enhanced Raman spectra of a bifunctional Raman
      reporter, 2-mercaptobenzimidazole, has been found to be responsive exclusively
      towards Cu(2+) ions while the reporter remains anchored on the Au nanoparticle
      surface. Thus a specific Cu(2+)-ion-detection protocol emerges. The simplicity,
      sensitivity, and reproducibility of the method allow routine and quantitative
      detection of Cu(2+) ions. An interference study involving a wide number of other
      metal ions shows the procedure to be uniquely selective and analytically
      rigorous. A theoretical study was carried out to corroborate the experimental
      results. Finally, the method is promising for real-time assessment of Cu(2+) ions
      in aqueous samples and also has the ability to discriminate Cu(I) and Cu(II) ions
      in solution.

PMID- 22473801
TI  - Catalytic asymmetric mono-fluorination of alpha-keto esters: synthesis of
      optically active beta-fluoro-alpha-hydroxy and beta-fluoro-alpha-amino acid
      derivatives.

PMID- 22473802
TI  - (S)-Naproxen as a platform to develop chiral derivatizing reagent for reversed
      phase high-performance liquid chromatographic enantioseparation of analytes
      having a carbonyl functional group.
AB  - (S)-Naproxen was used to synthesize a chiral reagent, (S)-2-(6-methoxynaphthalen
      2-yl)propanehydrazide, by itsreaction with hydrazine hydrate in the presence of
      dicyclohexylcarbodiimide as coupling agent. The reagent was characterized and its
      chiral purity was established. It was used as a chiral derivatizing reagent for
      the synthesis of hydrazone diastereomers, under microwave irradiation, of certain
      chiral aldehydes and ketones. The respective diastereomers were separated by
      reversed-phase high-performance liquid chromatography using a binary solvent
      combination containing trifluoroacetic acid. The diastereomers were detected at
      231 nm. The method was validated for accuracy, precision, and limit of detection
      (LOD). For a series of hydrazones the LOD was found to be in the range 1.62-1.65
      pmol/mL.

PMID- 22473803
TI  - Ferroportin1 in hepatocytes and macrophages is required for the efficient
      mobilization of body iron stores in mice.
AB  - The liver is a major site of iron storage where sequestered iron can be actively
      mobilized for utilization when needed elsewhere in the body. Currently,
      hepatocyte iron efflux mechanisms and their relationships to macrophage iron
      recycling during the control of whole-body iron homeostasis are unclear. We
      hypothesized that the iron exporter, ferroportin1 (Fpn1), is critical for both
      iron mobilization from hepatocytes and iron recycling from macrophages. To test
      this, we generated hepatocyte-specific Fpn1 deletion mice (Fpn1(Alb/Alb) ) and
      mice that lacked Fpn1 in both hepatocytes and macrophages
      (Fpn1(Alb/Alb;LysM/LysM) ). When fed a standard diet, Fpn1(Alb/Alb) mice showed
      mild hepatocyte iron retention. However, red blood cell (RBC) counts and
      hemoglobin (Hb) levels were normal, indicating intact erythropoiesis. When fed an
      iron-deficient diet, Fpn1(Alb/Alb) mice showed impaired liver iron mobilization
      and anemia, with much lower RBC and Hb levels than Fpn1(flox/flox) mice on the
      same diet. Using a strategy where mice were preloaded with differing amounts of
      dietary iron before iron deprivation, we determined that erythropoiesis in
      Fpn1(Alb/Alb) and Fpn1(flox/flox) mice depended on the balance between storage
      iron and iron demands. On a standard diet, Fpn1(Alb/Alb;LysM/LysM) mice displayed
      substantial iron retention in hepatocytes and macrophages, yet maintained intact
      erythropoiesis, implying a compensatory role for intestinal iron absorption. In
      contrast, when Fpn1(Alb/Alb;LysM/LysM) mice were fed an iron-deficient diet, they
      developed severe iron-deficiency anemia, regardless of their iron storage status.
      Thus, Fpn1 is critical for both hepatocyte iron mobilization and macrophage iron
      recycling during conditions of dietary iron deficiency. CONCLUSION: Our data
      reveal new insights into the relationships between Fpn1-mediated iron
      mobilization, iron storage, and intestinal iron absorption and how these
      processes interact to maintain systemic iron homeostasis.

PMID- 22473804
TI  - Anatomical basis of sun compass navigation I: the general layout of the monarch
      butterfly brain.
AB  - Each fall, eastern North American monarch butterflies (Danaus plexippus) use a
      time-compensated sun compass to migrate to their overwintering grounds in central
      Mexico. The sun compass mechanism involves the neural integration of skylight
      cues with timing information from circadian clocks to maintain a constant
      heading. The neuronal substrates for the necessary interactions between compass
      neurons in the central complex, a prominent structure of the central brain, and
      circadian clocks are largely unknown. To begin to unravel these neural
      substrates, we performed 3D reconstructions of all neuropils of the monarch brain
      based on anti-synapsin labeling. Our work characterizes 21 well-defined neuropils
      (19 paired, 2 unpaired), as well as all synaptic regions between the more
      classically defined neuropils. We also studied the internal organization of all
      major neuropils on brain sections, using immunocytochemical stainings against
      synapsin, serotonin, and gamma-aminobutyric acid. Special emphasis was placed on
      describing the neuroarchitecture of sun-compass-related brain regions and
      outlining their homologies to other migratory species. In addition to finding
      many general anatomical similarities to other insects, interspecies comparison
      also revealed several features that appear unique to the monarch brain. These
      distinctive features were especially apparent in the visual system and the
      mushroom body. Overall, we provide a comprehensive analysis of the brain anatomy
      of the monarch butterfly that will ultimately aid our understanding of the
      neuronal processes governing animal migration.

PMID- 22473806
TI  - Reconstruction of hand injuries with multiple metacarpal defects using free
      fibular osteoseptocutaneous flap.
AB  - Hand injuries with multiple metacarpal involvements often include midpalmar
      muscle, extensor tendon, and skin defects. Reconstruction method is decided
      according to the type and amount of structures to be restored. Bone
      reconstruction and resurfacing of the skin is regarded as priority, and
      restoration of tendon function and joint mobility can be left for further
      procedures. An ideal flap for such defects should provide bone for multiple
      metacarpal defects and a large enough skin paddle. Such flaps are few, and one of
      the most suitable of them all is the free fibular osteoseptocutaneous flap (free
      FOSCF). In this report, our experience with the use of free FOSCF for
      reconstruction of the mutilating hand injury in five patients with extensive skin
      integument and metacarpal involvement has been presented. Total lengths of
      fibular flaps were averagely 11 cm in length and were divided into averagely 2.4
      segments. Average dimensions of the skin paddles were 7.75 * 8.75 cm. Although
      the nature of the devastating traumas limited the ultimate functional recovery;
      wound closure, stability, and various degrees of mobility were restored in all
      patients. In our experience, reconstruction with free FOSCF proved to be an
      effective tool in mutilating hand injuries with metacarpal involvement.

PMID- 22473807
TI  - Paper-based supercapacitors for self-powered nanosystems.
AB  - Energy storage on paper: paper-based, all-solid-state, and flexible
      supercapacitors were fabricated, which can be charged by a piezoelectric
      generator or solar cells and then discharged to power a strain sensor or a blue
      light-emitting diode, demonstrating its efficient energy management in self
      powered nanosystems.

PMID- 22473808
TI  - Perception of juvenile delinquents of group therapy approaches.
AB  - The present study focuses on juvenile delinquents' perception of two procedures
      used in group therapy. Eleven juvenile delinquents, participants of a probation
      program, were asked to share their experience with group therapy. Using
      Interpretative Phenomenological Analysis of the interviews with the participants,
      the specifics of verbal and action procedures were examined. Verbal procedures
      offer clients a greater opportunity for emotional experience and subsequent
      cognitive processing of the experience leading to personal growth. The action
      procedures are, in contrast, a way of deepening the client's contact with other
      group members. They enable subjects to relax by helping them distance themselves
      from everyday problems. 

PMID- 22473809
TI  - Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma,
      and curcumin: a randomized, double-blind placebo-controlled cross-over 4g study
      and an open-label 8g extension study.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple
      myeloma (SMM) represent useful models for studying multiple myeloma precursor
      disease, and for developing early intervention strategies. Administering a 4g
      dose of curcumin, we performed a randomised, double-blind placebo-controlled
      cross-over study, followed by an open-label extension study using an 8g dose to
      assess the effect of curcumin on FLC response and bone turnover in patients with
      MGUS and SMM. 36 patients (19 MGUS and 17 SMM) were randomised into two groups:
      one received 4g curcumin and the other 4g placebo, crossing over at 3 months. At
      completion of the 4g arm, all patients were given the option of entering an open
      label, 8g dose extension study. Blood and urine samples were collected at
      specified intervals for specific marker analyses. Group values are expressed as
      mean +/- 1 SD. Data from different time intervals within groups were compared
      using Student's paired t-test. 25 patients completed the 4g cross-over study and
      18 the 8g extension study. Curcumin therapy decreased the free light-chain ratio
      (rFLC), reduced the difference between clonal and nonclonal light-chain (dFLC)
      and involved free light-chain (iFLC). uDPYD, a marker of bone resorption,
      decreased in the curcumin arm and increased on the placebo arm. Serum creatinine
      levels tended to diminish on curcumin therapy. These findings suggest that
      curcumin might have the potential to slow the disease process in patients with
      MGUS and SMM.

PMID- 22473810
TI  - Probing of C-terminal lysine variation in a recombinant monoclonal antibody
      production using Chinese hamster ovary cells with chemically defined media.
AB  - C-terminal lysine (C-K) variants are commonly observed in therapeutic monoclonal
      antibodies and recombinant proteins. Heterogeneity of C-K residues is believed to
      result from varying degree of proteolysis by endogenous carboxypeptidase(s)
      during cell culture production. The achievement of batch-to-batch culture
      performance and product quality reproducibility is a key cell culture development
      criterion. Understanding the operational parameters affecting C-K levels provides
      valuable insight into the cell culture process. A CHO cell line X expressing a
      recombinant antibody was selected as the model cell line due to the exhibited
      sensitivity of its C-K level to the process conditions. A weak cation exchange
      chromatography (WCX) method with or without carboxypeptidase B (CpB) treatment
      was developed to monitor the C-K level for in-process samples. The effects of
      operating conditions (i.e., temperature and culture duration) and media trace
      elements (copper and zinc) on C-K variants were studied. The dominant effect on C
      K level was identified as the trace elements concentration. Specifically,
      increased C-K levels were observed with increase of copper concentration and
      decrease of zinc concentration in chemically defined medium. Further, a
      hypothesis for C-K processing with intracellular and extracellular
      carboxypeptidase activity was proposed, based on preliminary intracellular
      carboxypeptidase Western blot results and the extracellular HCCF holding study.

PMID- 22473812
TI  - Psychiatric comorbidity is associated with increased skill deficits.
AB  - Recent research on psychotherapy has focused on the development and evaluation of
      disorder-specific treatments. Even though much progress has been made, treatments
      have not yet reached an ideal level of effectiveness. One reason for this could
      be the systematic overlap and high comorbidity between mental disorders.
      Consequently, a new trend has been the examination of transdiagnostic factors in
      order to conceptualize psychopathology and develop treatment tools. One approach
      is to strengthen skills (e.g., emotion regulation) that are relevant in different
      mental disorders. The unique feature of this study is the simultaneous
      examination of several skills and their relation to psychopathology. Therefore,
      the current study investigated the skill levels of different groups of inpatients
      (tinnitus, tinnitus/unipolar mood disorder and anxiety/unipolar mood disorder)
      and normal controls (n = 124). Participants were evaluated with the
      'operationalized assessment of skills interview'. This interview allows the
      simultaneous assessment of seven skills (problem solving, social competence,
      stress management, emotion regulation, relaxation ability, self-efficacy and self
      esteem) that are relevant for treatment planning. The results confirm negative
      correlations between skills and the number of comorbid diagnoses. Multivariate
      analyses identified significant differences in skill levels between clinical
      sample and normal controls. Furthermore, within the clinical sample, there were
      significant differences in skill levels and skill profiles between the different
      clinical subsamples. To conclude, the improvement of skills that can support
      recovery from mental disorders is especially relevant for patients with multiple
      diagnoses. The authors suggest assessing the different skills prior to treatment
      and considering the skill profiles when planning interventions. KEY PRACTITIONER
      MESSAGE: Lower skill levels are associated with higher comorbidity and higher
      level of psychopathology of patients. There is evidence for specific skill
      profiles within different clinical subsamples. The improvement of skills that can
      impact recovery from mental disorders is especially relevant for patients with
      multiple diagnoses. It makes sense to assess the different skills independently
      and consider them separately when planning interventions.

PMID- 22473811
TI  - Zinc in the central nervous system: From molecules to behavior.
AB  - The trace metal zinc is a biofactor that plays essential roles in the central
      nervous system across the lifespan from early neonatal brain development through
      the maintenance of brain function in adults. At the molecular level, zinc
      regulates gene expression through transcription factor activity and is
      responsible for the activity of dozens of key enzymes in neuronal metabolism. At
      the cellular level, zinc is a modulator of synaptic activity and neuronal
      plasticity in both development and adulthood. Given these key roles, it is not
      surprising that alterations in brain zinc status have been implicated in a wide
      array of neurological disorders including impaired brain development,
      neurodegenerative disorders such as Alzheimer's disease, and mood disorders
      including depression. Zinc has also been implicated in neuronal damage associated
      with traumatic brain injury, stroke, and seizure. Understanding the mechanisms
      that control brain zinc homeostasis is thus critical to the development of
      preventive and treatment strategies for these and other neurological disorders.

PMID- 22473813
TI  - A miniaturized sensor consisting of concentric metallic nanorings on the end
      facet of an optical fiber.
AB  - A polarization-independent optical sensor is created by fabricating a concentric
      gold ring grating with a period of 900 nm on the end facet of an optical fiber.
      The sensing function of this miniaturized device is realized by sending white
      light as a probe to the gold rings and collecting the response signal in the back
      reflection through the optical fiber. A pronounced peak due to the Rayleigh
      anomaly of the gold ring grating is observed in the reflection spectrum, the
      center wavelength of which is sensitive to the change in the environmental
      refractive index of the fiber end facet. Theoretical analysis not only shows
      excellent agreement with the experimental results, but also gives insights into
      the mechanisms of this kind of sensor. Using the center position of the Rayleigh
      peak as the response signal, a high sensitivity dlambda/dn of 900 nm per unity
      refractive index is realized for this sensor and a resolution of Deltan/n ~ 1% is
      demonstrated in preliminary experiments. The sensitivity is solely determined by
      the period of the grating.

PMID- 22473814
TI  - Organic and conventional nonflavored yogurts from the Italian market: study on
      sensory profiles and consumer acceptability.
AB  - BACKGROUND: The sensory properties of food products are an important success
      factor, especially in the organic market, where many producers and distributors
      of organic food claim superior taste for their products compared to the
      conventional alternative. For this reason consumer expectations and preferences,
      as well as the sensory properties of conventional and organic yogurt, have to be
      investigated in depth. In this work, the sensory profiling and consumer data of
      six nonflavored organic and conventional Italian yogurts were elaborated. Some
      results on the data segmentation (heavy and light users of organic food) and on
      the effect of information on liking (blind and labeled test) were obtained.
      Multivariate analysis was carried out to study how the sensory characteristics of
      'natural yogurts' drive consumer liking. RESULTS: Consumers' preferences were
      oriented towards a creamy mouthfeel and smooth visual appearance and for a less
      acid and fresh taste. In particular, a conventional yogurt was the least
      accepted, because it was not creamy enough. This paper shows there is room to
      improve unflavored yogurt to better meet consumer expectations. CONCLUSION:
      Sensory profiling did not allow a distinction in odor/taste/texture between
      organic and conventional samples. However, three of four organic samples were in
      the region of highest consumer acceptability, fitting well consumers' preference.
      There was no clear tendency that heavy or light users scored differently in the
      blind and labeled tests regarding overall liking but, for all, the most liked
      conventional yogurt scored higher when labeled as organic.

PMID- 22473815
TI  - Middle-of-the-night PCI does not affect subsequent day PCI success and
      complication rates by the same operator.
AB  - OBJECTIVE: To determine the impact of percutaneous coronary interventions (PCI)
      performed during late-night hours on next day PCI performance by the same
      interventional cardiologist. BACKGROUND: There is little data regarding the
      effects of sleep deprivation on interventional cardiologists performing PCIs.
      METHODS: All primary PCIs from January 1, 2005 to December 31, 2009 between 11 PM
      and 7 AM were identified. All PCIs performed during the subsequent work day by
      the same interventionists were included in the sleep-deprived group. All other
      PCIs were included in the non-sleep-deprived group. Data were entered
      prospectively into the American College of Cardiology National Cardiovascular
      Data Registry (NCDR). The two groups were compared with respect to efficacy and
      safety endpoints. RESULTS: During the 5-year period, 3,944 PCIs were performed by
      four operators, including 3,644 non-sleep-deprived cases and 167 sleep-deprived
      cases. The two groups were similar with respect to demographics, comorbidities,
      and procedural characteristics. There were more intraprocedural deaths in the
      sleep-deprived group (1.2% vs. 0.2%, P = 0.04); however, the adjusted odds ratio
      (OR) was nonsignificant (OR = 6.83, 95% confidence interval [CI] = 0.66-39.63, P
      = 0.11). Excessive bleeding at the arterial access site in the non-sleep-deprived
      group was more frequent (2.7% vs. 0%, P = 0.02). There were no differences in the
      combined safety or efficacy endpoints between the two groups. CONCLUSION: In this
      single-center study, we found no evidence that middle-of-the night procedures
      adversely affect safety or efficacy of procedures done the next day by the same
      operator.

PMID- 22473816
TI  - Challenges, coping strategies, and unmet needs of families with a child with
      autism spectrum disorder in Goa, India.
AB  - Autism Spectrum Disorders (ASD) are increasingly recognized in developing
      countries like India. However, little is known about the experiences of parents
      raising a child with ASD. This study aimed to describe the experiences of
      families in Goa, India with a view to understanding the unmet needs of families
      raising a child with ASD. Twenty in-depth interviews and nine focus group
      discussions were carried out with families of children with ASD and key community
      stakeholders such as special educators, teachers, and parents of typically
      developing children. This qualitative data was triangulated to explore the
      experiences, life impact, and unmet needs of raising a child with ASD. Key
      findings suggest that raising a child with ASD puts a tremendous strain on
      families due to competing commitments, often leading to initial social withdrawal
      with later reintegration into social networks. Second, the impact is
      multidimensional, involving the personal sphere but also extending into the wider
      community with negative experiences of discrimination. Third, parents actively
      respond to these challenges through a range of approaches with help from existing
      and new social support networks and health care providers. Fourth, professionals
      from the health, education, and religious sectors have a low awareness of the
      unique needs of families living with ASD which leads to a considerable economic
      and emotional burden on families. Finally, as a consequence of these experiences,
      several unmet needs can be identified, notably for supporting increasingly
      isolated families and the limited access to multidisciplinary evidence-based
      services for ASD. Autism Res 2012, 5: 190-200. (c) 2012 International Society for
      Autism Research, Wiley Periodicals, Inc.

PMID- 22473817
TI  - Norisoboldine inhibits the production of interleukin-6 in fibroblast-like
      synoviocytes from adjuvant arthritis rats through PKC/MAPK/NF-kappaB-p65/CREB
      pathways.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine secreted by macrophages and others
      and it has been proven to be a potential therapeutic target of RA. Norisoboldine
      (NOR) is the main isoquinoline alkaloid constituent in the dry roots of Lindera
      aggregata (Sims) Kosterm. (L. strychnifolia Vill.), which has long been used in
      traditional Chinese medicine for treating RA and other diseases. Our previous
      studies indicated that NOR was able to attenuate inflammation and joint
      destruction in collagen II-induced arthritis of mice. To further recognize the
      anti-rheumatoid potentials of NOR, the present study addressed whether and how
      NOR interfered with IL-6 production from fibroblast-like synoviocytes (FLS), key
      effector cells in the development and progression of RA. FLS, obtained from the
      synovial tissues of rats with adjuvant arthritis, showed incremental release of
      IL-6 after stimulated with IL-1beta in vitro. NOR (10, 30, and 60 uM) could
      reduce the production of IL-6 in a concentration-dependent manner. It also down
      regulated the phosphorylations of mitogen-activated protein kinases (MAPKs),
      protein kinase C (PKC), and transcriptional factor nuclear factor-kappaB (NF
      kappaB)-p65 (ser 276) as well as cAMP response element-binding protein (CREB) in
      FLS. By using specific inhibitors, PKC was shown to be the upstream protein of
      MAPKs, and p38 MAPK was at the upstream of CREB. It was concluded that preventing
      IL-6 release from FLS might be an important mechanism for NOR displaying anti-RA
      property, and the action of NOR was relative to inhibition of PKC/MAPKs/p65/CREB
      pathways.

PMID- 22473818
TI  - The reaction of sulfenic acids with peroxyl radicals: insights into the radical
      trapping antioxidant activity of plant-derived thiosulfinates.
AB  - Sulfenic acids play a prominent role in biology as key participants in cellular
      signaling relating to redox homeostasis, in the formation of protein-disulfide
      linkages, and as the central players in the fascinating organosulfur chemistry of
      the Allium species (e.g., garlic). Despite their relevance, direct measurements
      of their reaction kinetics have proven difficult owing to their high reactivity.
      Herein, we describe the results of hydrocarbon autoxidations inhibited by the
      persistent 9-triptycenesulfenic acid, which yields a second order rate constant
      of 3.0*10(6)  M(-1)  s(-1) for its reaction with peroxyl radicals in PhCl at 30 
      degrees C. This rate constant drops 19-fold in CH(3)CN, and is subject to a
      significant primary deuterium kinetic isotope effect, k(H)/k(D) = 6.1, supporting
      a formal H-atom transfer (HAT) mechanism. Analogous autoxidations inhibited by
      the Allium-derived (S)-benzyl phenylmethanethiosulfinate and a corresponding
      deuterium-labeled derivative unequivocally demonstrate the role of sulfenic acids
      in the radical-trapping antioxidant activity of thiosulfinates, through the rate
      determining Cope elimination of phenylmethanesulfenic acid (k(H)/k(D) ~ 4.5) and
      its subsequent formal HAT reaction with peroxyl radicals (k(H)/k(D) ~ 3.5). The
      rate constant that we derived from these experiments for the reaction of
      phenylmethanesulfenic acid with peroxyl radicals was 2.8*10(7)  M(-1)  s(-1); a
      value 10-fold larger than that we measured for the reaction of 9
      triptycenesulfenic acid with peroxyl radicals. We propose that whereas
      phenylmethanesulfenic acid can adopt the optimal syn geometry for a 5-centre
      proton-coupled electron-transfer reaction with a peroxyl radical, the 9
      triptycenesulfenic is too sterically hindered, and undergoes the reaction instead
      through the less-energetically favorable anti geometry, which is reminiscent of a
      conventional HAT.

PMID- 22473819
TI  - Liver tumorigenicity promoted by microRNA-221 in a mouse transgenic model.
AB  - MicroRNA-221 (miR-221) is one of the most frequently and consistently up
      regulated microRNAs (miRNAs) in human cancer. It has been hypothesized that miR
      221 may act as a tumor promoter. To demonstrate this, we developed a transgenic
      (TG) mouse model that exhibits an inappropriate overexpression of miR-221 in the
      liver. Immunoblotting and immunostaining confirmed a concomitant down-regulation
      of miR-221 target proteins. This TG model is characterized by the emergence of
      spontaneous nodular liver lesions in approximately 50% of male mice and by a
      strong acceleration of tumor development in 100% of mice treated with
      diethylnitrosamine. Similarly to human hepatocellular carcinoma, tumors are
      characterized by a further increase in miR-221 expression and a concomitant
      inhibition of its target protein-coding genes (i.e., cyclin-dependent kinase
      inhibitor [Cdkn]1b/p27, Cdkn1c/p57, and B-cell lymphoma 2-modifying factor). To
      validate the tumor-promoting effect of miR-221, we showed that in vivo delivery
      of anti-miR-221 oligonucleotides leads to a significant reduction of the number
      and size of tumor nodules. CONCLUSIONS: This study not only establishes that miR
      221 can promote liver tumorigenicity, but it also establishes a valuable animal
      model to perform preclinical investigations for the use of anti-miRNA approaches
      aimed at liver cancer therapy.

PMID- 22473820
TI  - Development of rapid and simultaneous quantitative method for green tea catechins
      on the bioanalytical study using UPLC/ESI-MS.
AB  - A rapid and quantitative analytical method for the simultaneous determination of
      green tea catechins using ultra-performance liquid chromatography/electrospray
      ionization-mass spectrometry was developed. Total analytical run time was 3.5 min
      for the detection of (-)-epicatechin (EC), (-)-epicatechin-3-O-gallate (ECG), (-)
      epigallocatechin (EGC), (-)-epigallocatechin-3-O-gallate (EGCG) and myricetin as
      the internal standard (IS) in rat plasma. The calibration curves were linear over
      the range of 10-5000 ng/mL for all the catechins. The inter- and intra-day
      precision (relative standard deviation) and accuracy (percentage deviation) of
      the method were both lower than 10%. The average extraction recoveries in plasma
      ranged from 68.5 to 86.5%, and the lower limits of quantification of EC, EGC, ECG
      and EGCG were 10 ng/mL with a signal-to-noise ratio of >10. The assay developed
      was successfully applied to a pharmacokinetic study of catechins following
      intravenous and intragastric administrations of green tea extract in rats. Plasma
      concentrations of four catechins were detected up to 5-24 h after administration,
      and the pharmacokinetic parameters of catechins were in agreement with previous
      studies. From these findings, taken together with the high productivity and
      precision, the developed method could be a reliable and reproducible tool for the
      evaluation of pharmacokinetic properties of catechins.

PMID- 22473821
TI  - Functional fibrinogen to platelet ratio using thromboelastography as a predictive
      parameter for thrombotic complications following free tissue transfer surgery: a
      preliminary study.
AB  - BACKGROUND: Microvascular free tissue transfer in head and neck surgery has
      become an indispensable tool. Anastomotic thrombosis is one of the leading causes
      of flap failure; however, there are no validated methods to accurately identify
      and quantify those patients most at risk of thrombotic complications. The aim of
      this study was to determine if functional fibrinogen to platelet ratio using
      thrombelastography could preoperatively identify patients at risk of thrombotic
      complications. MATERIALS AND METHODS: Twenty nine patients undergoing free tissue
      transfer surgery for head and neck pathology underwent routine TEG(r) analysis,
      with calculation of functional fibrinogen to platelet ratio at induction of
      anesthesia. All perioperative thrombotic complications were recorded and
      crossreferenced with preoperative ratios. Data was further compared to results
      obtained from 42 healthy volunteers. RESULTS: The mean functional fibrinogen to
      platelet ratio was significantly higher in the surgery group compared to healthy
      volunteers. Of the 29 patients studied, 31% (n = 9) had some form of thrombotic
      event, with all but one patient having a ratio >=42% (mean 47% +/- 7%). For those
      patients without thrombotic events, the mean ratio was 37% +/- 5%. CONCLUSION: A
      functional fibrinogen to platelet ratio above 42% as measured by TEG(r) may be
      useful in identifying those patients likely to develop thrombotic complication.

PMID- 22473823
TI  - Mild and efficient C2-alkenylation of indoles with alkynes catalyzed by a cobalt
      complex.

PMID- 22473822
TI  - Protein oxidation in Huntington disease.
AB  - Huntington disease (HD) is an inherited neurodegenerative disorder caused by
      expansion of CAG repeats in the huntingtin gene, affecting initially the striatum
      and progressively the cortex. Oxidative stress, and consequent protein oxidation,
      has been described as important to disease progression. This review focuses on
      recent advances in the field, with a particular emphasis on the identified target
      proteins and the role that their oxidation has or might have in the
      pathophysiology of HD. Oxidation and the resulting inactivation and/or
      degradation of important proteins can explain the impairment of several metabolic
      pathways in HD. Oxidation of enzymes involved in ATP synthesis can account for
      the energy deficiency observed. Impairment of protein folding and degradation can
      be due to oxidation of several heat shock proteins and Valosin-containing
      protein. Oxidation of two enzymes involved in the vitamin B6 metabolism could
      result in decreased availability of pyridoxal phosphate, which is a necessary
      cofactor in transaminations, the kynurenine pathway and the synthesis of
      glutathione, GABA, dopamine and serotonin, all of which have a key role in HD
      pathology. In addition, protein oxidation often contributes to oxidative stress,
      aggravating the molecular damage inside the cell.

PMID- 22473824
TI  - Detergent-free formation and physicochemical characterization of nanosized lipid
      polymer complexes: Lipodisq.

PMID- 22473825
TI  - Controlling trisulfide modification in recombinant monoclonal antibody produced
      in fed-batch cell culture.
AB  - Molecular heterogeneity was detected in a recombinant monoclonal antibody (IgG1
      mAb) due to the presence of a trisulfide linkage generated by the post
      translational insertion of a sulfur atom into disulfide bonds at the heavy-heavy
      and heavy-light junctions. This molecular heterogeneity had no observable effect
      on antibody function. Nevertheless, to minimize the heterogeneity of the IgG1 mAb
      from run-to-run, an understanding of the impact of cell culture process
      conditions on trisulfide versus disulfide linkage formation was desirable. To
      investigate variables that might impact trisulfide formation, cell culture
      parameters were varied in bench-scale bioreactor studies. Trisulfide analysis of
      the samples from these runs revealed that the trisulfide content in the bond
      between heavy and light chains varied considerably from <1% to 39%. Optimizing
      the culture duration and feeding strategy resulted in more consistent trisulfide
      levels. Cysteine concentration in the feed medium had a direct correlation with
      the trisulfide level in the product. Systematic studies revealed that cysteine in
      the feed and the bioreactor media was contributing hydrogen sulfide which reacted
      with the IgG1 mAb in the supernatant leading to the insertion of sulfur atom and
      formation of a trisulfide bond. Cysteine feed strategies were developed to
      control the trisulfide modification in the recombinant monoclonal antibody.

PMID- 22473826
TI  - Studying polymer/fullerene intermixing and miscibility in laterally patterned
      films with X-ray spectromicroscopy.
AB  - Films of the fullerene derivatives [6,6]-phenyl-C(61)-butyric acid methyl ester
      (PC(61) BM) and [6,6]-phenyl-C(71)-butyric acid methyl ester (PC(71) BM) are
      patterned on silicon nitride membranes using photolithography to study, with X
      ray spectromicroscopy, the lateral, solid-state diffusion of fullerene
      derivatives into conjugated polymer films. After patterning of the fullerene
      film, a film of conjugated polymer is laminated on top and the structure is
      annealed in order to study lateral intermixing and facilitate measurement of
      fullerene miscibility. Lateral intermixing of polymer and fullerene readily
      occurs for poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT)
      and regiorandom poly(3-hexylthiophene) (RRa-P3HT). A 42 wt.% miscibility of
      PC(61) BM in PBTTT is measured, while miscibilities of 20 and 41 wt.% are
      measured for PC(61) BM and PC(71) BM, respectively, in RRa-P3HT, thereby
      demonstrating a significant difference in the miscibilities of these two
      fullerene derivatives. For regioregular poly(3-hexylthiophene) (RR-P3HT),
      incomplete lateral intermixing of fullerene and RR-P3HT is observed with PCBM
      crystallite formation competing with the lateral diffusion of PCBM molecules into
      the polymer film.

PMID- 22473827
TI  - Hydroxyurea-related toxicity in 3,411 patients with Ph'-negative MPN.
AB  - Hydroxyurea (Hydroxycarbamide; HU) is commonly used for the long-term treatment
      of patients with Philadelphia-chromosome negative chronic myeloproliferative
      neoplasms (MPNs). It is considered a first-choice agent for the treatment of
      these disorders as underlined by the European Leukemia Net Consensus Conference
      [1], although it is formally approved for this indication in some countries only.
      The drug is reportedly well tolerated in the large majority of subjects, although
      systemic and/or localized toxicities have been reported. Consensus criteria for
      definition of "intolerance" to HU have been described;patients who develop
      intolerance are candidate for second-line therapy and, more recently, for
      investigational drugs. However, no epidemiologic information about the occurrence
      of the most clinically significant HU-associated adverse events is yet available.
      In this study, the authors report on a multicenter series of 3,411 patients who
      were treated with HU among which 184, accounting for 5% of total, developed
      significant drug-related toxicities. These data provide an estimate of the
      frequency and a detailed characterization of clinically significant HU-related
      toxicities; these information have relevance for the management of MPN patients
      who require second-line therapy after developing HU-related intolerance.

PMID- 22473828
TI  - Development of tyrosine hydroxylase-immunoreactive cell populations and fiber
      pathways in the brain of the dogfish Scyliorhinus canicula: new perspectives on
      the evolution of the vertebrate catecholaminergic system.
AB  - Developmental studies of the central catecholaminergic (CA) system are essential
      for understanding its evolution. To obtain knowledge about the CA system in
      chondrichthyans, an ancient gnathostome group, we used immunohistochemical
      techniques for detecting tyrosine hydroxylase (TH), the initial rate-limiting
      enzyme of the CA synthesis, to study: 1) the neuromery of developing TH
      immunoreactive (ir) neuronal populations, 2) the development of TH-ir
      innervation, and 3) the organization of TH-ir cells and fibers in the brain of
      postembryonic stages of the shark Scyliorhinus canicula. The first TH-ir cells
      appeared in the hypothalamus and rostral diencephalon (suprachiasmatic, posterior
      recess and posterior tubercle nuclei at embryonic stage 26, and dorsomedial
      hypothalamus at stage 28); then in more caudal basal regions of the diencephalon
      and rostral mesencephalon (substantia nigra/ventral tegmental area); and later on
      in the anterior (locus coeruleus/nucleus subcoeruleus) and posterior (vagal lobe
      and reticular formation) rhombencephalon. The appearance of TH-ir cells in the
      telencephalon (pallium) was rather late (stage [S]31) with respect to the other
      TH-ir prosencephalic populations. The first TH-ir fibers arose from cells of the
      posterior tubercle (S30) and formed recognizable ascending (toward dorsal and
      rostral territories) and descending pathways at S31. When the second half of
      embryonic development started (S32), TH-ir fibers innervated most brain areas,
      and nearly all TH-ir cell groups of the postembryonic brain were already
      established. This study provides key information about the evolution of the
      developmental patterns of central CA systems in fishes and thus may help in
      understanding how the vertebrate CA systems have evolved.

PMID- 22473829
TI  - Optic tectum morphogenesis: a step-by-step model based on the temporal-spatial
      organization of the cell proliferation. Significance of deterministic and
      stochastic components subsumed in the spatial organization.
AB  - BACKGROUND: Cell proliferation plays an important morphogenetic role. This work
      analyzes the temporal-spatial organization of cell proliferation as an attempt to
      understand its contribution to the chick optic tectum (OT) morphogenesis.
      RESULTS: A morphogenetic model based on space-dependent differences in cell
      proliferation is presented. Step1: a medial zone of high mitotic density (mZHMD)
      appears at the caudal zone. Step2: the mZHMD expands cephalically forming the
      dorsal curvature and then duplicates into two bilateral ZHMDs (bZHMD). Step3: the
      bZHMDs move toward the central region of each hemitectum. Step4: the planar
      expansion of both bZHMD and a relative decrement in the dorsal midline growth
      produces a dorsal medial groove separating the tectal hemispheres. Step5: a
      relative caudal displacement of the bZHMDs produces the OT caudal curvature.
      Numerical sequences derived from records of mitotic cells spatial coordinates,
      analyzed as stochastic point processes, show that they correspond to 1/f((beta))
      processes. The spatial organization subsumes deterministic and stochastic
      components. CONCLUSIONS: The deterministic component describes the presence of a
      long-range influence that installs an asymmetric distribution of cell
      proliferation, i.e., an asymmetrically located ZHMD that print space-dependent
      differences onto the tectal corticogenesis. The stochastic component reveals
      short-range anti-correlations reflecting spatial clusterization and
      synchronization between neighboring cells.

PMID- 22473830
TI  - CdS nanoparticles-enhanced chemiluminescence and determination of baicalin in
      pharmaceutical preparations.
AB  - CdS nanoparticles (CdS NPs) of different sizes were synthesized by the citrate
      reduction method. It was found that CdS NPs could enhance the chemiluminescence
      (CL) of the luminol-potassium ferricyanide system and baicalin could inhibit CdS
      NPs-enhanced luminol-potassium ferricyanide CL signals in alkaline solution.
      Based on this inhibition, a flow-injection CL method was established for
      determination of baicalin in pharmaceutical preparations and human urine samples.
      Under optimized conditions, the linear range for determination of baicalin was
      5.0 x 10(-6) to 1.0 x 10(-3) g/L. The detection limit at a signal-to-noise ratio
      of 3 was 1.7 x 10(-6) g/L. CL spectra, UV-visible spectra and transmission
      electron microscopy (TEM) were used to investigate the CL mechanism. The method
      described is simple, selective and obviates the need of extensive sample
      pretreatment.

PMID- 22473831
TI  - Effectiveness of two formulations of oral olanzapine in patients with
      schizophrenia or bipolar disorder in a natural setting: results from a 1-year
      European observational study.
AB  - OBJECTIVE: This study aims to assess the proportion of patients with
      schizophrenia or bipolar disorder who discontinued treatment with one of two oral
      formulations of olanzapine within 12 months in outpatient settings in Germany,
      Greece, and France. METHODS: This 1-year, prospective, observational study
      included patients who had recently initiated treatment with olanzapine-coated
      tablets (OC) or the orodispersible (OD) formulation. Primary endpoint was
      olanzapine discontinuation for any reason. Clinical and functional status were
      also evaluated. RESULTS: Out of 927 enrolled patients, 903 were included in the
      analyses (612 patients with schizophrenia, 291 with bipolar disorder). Within 12
      months, 46 of 903 patients discontinued olanzapine. Most (95%) patients remained
      on olanzapine for 12 months with similar rates for patients with either diagnosis
      (94.5% for schizophrenia, 94.9% for bipolar disorder) and for both formulations
      (93.7% with OC, 95.3% with OD). The only factor significantly associated with
      time to discontinuation was baseline disease severity. Patients with more severe
      disease at baseline had a lower discontinuation risk. There were significant
      improvements in functioning and well-being and non-significant improvements in
      therapeutic alliance and compliance. CONCLUSIONS: No significant difference was
      seen between discontinuation rates of the two formulations. Higher baseline
      severity was associated with a lower discontinuation rate.

PMID- 22473832
TI  - Initial multi-institutional experience with transoral robotic surgery.
AB  - OBJECTIVE: To assess the initial experience for transoral robotic surgery (TORS),
      as observed in the French TORS group. STUDY DESIGN: A multi-institutional
      prospective cohort study. SETTING: Seven tertiary referral centers. SUBJECTS AND
      METHODS: One hundred thirty consecutive patients who were scheduled for a TORS
      between October 2008 and March 2011 were included. The operative times,
      conversion rates, morbidity, and alternatives were described. The serious adverse
      effects encountered were analyzed, and recommendations for avoiding them are
      specified. RESULTS: Most of the patients (65%) had a laryngeal (supraglottic)
      and/or hypopharyngeal resection. Thirty-nine of the 130 patients receiving TORS
      would have had a transoral laser resection as their alternative surgery. The
      tumor exposure was suboptimal in 26% of the cases. Six of the 130 patients needed
      conversion to an open approach. There were 15 postoperative hemorrhages and 2
      deaths due to posthemorrhage complications in patients with significant
      comorbidities at 9 and 18 days after the surgery. The median setup and procedure
      times were 52 +/- 46 and 90 +/- 92 minutes, respectively. The learning curve was
      characterized by better selection and management of potential patients.
      CONCLUSION: The visualization offered by the robotic assistance allowed transoral
      resections of tumors that were difficult to resect or unresectable by laser
      surgery. Self-assessment of surgical exposure and a decrease in the need to
      convert to an open procedure over time suggested improvement in TORS-related
      surgical skills. Nevertheless, strict patient selection is essential. Even with a
      minimally invasive approach, some patients will need a tracheostomy for safety
      reasons.

PMID- 22473833
TI  - Readability assessment of patient education materials from the American Academy
      of Otolaryngology--Head and Neck Surgery Foundation.
AB  - OBJECTIVE: Americans are increasingly turning to the Internet as a source of
      health care information. These online resources should be written at a level
      readily understood by the average American. This study evaluates the readability
      of online patient education information available from the American Academy of
      Otolaryngology--Head and Neck Surgery Foundation (AAO-HNSF) professional Web site
      using 7 different assessment tools that analyze the materials for reading ease
      and grade level of its target audience. STUDY DESIGN AND SETTING: Analysis of
      Internet-based patient education material from the AAO-HNSF Web site. METHODS:
      Online patient education material from the AAO-HNSF was downloaded in January
      2012 and assessed for level of readability using the Flesch Reading Ease, Flesch
      Kincaid Grade Level, SMOG grading, Coleman-Liau Index, Gunning-Fog Index, Raygor
      Readability Estimate graph, and Fry Readability graph. The text from each
      subsection was pasted as plain text into Microsoft Word document, and each
      subsection was subjected to readability analysis using the software package
      Readability Studio Professional Edition Version 2012.1. RESULTS: All health care
      education material assessed is written between an 11th grade and graduate reading
      level and is considered "difficult to read" by the assessment scales.
      CONCLUSIONS: Online patient education materials on the AAO-HNSF Web site are
      written above the recommended 6th grade level and may need to be revised to make
      them more easily understood by a broader audience.

PMID- 22473834
TI  - Linguistic pattern analysis of misspellings of typically developing writers in
      grades 1-9.
AB  - PURPOSE: A mixed-methods approach, evaluating triple word-form theory, was used
      to describe linguistic patterns of misspellings. METHOD: Spelling errors were
      taken from narrative and expository writing samples provided by 888 typically
      developing students in Grades 1-9. Errors were coded by category (phonological,
      orthographic, and morphological) and specific linguistic feature affected. Grade
      level effects were analyzed with trend analysis. Qualitative analyses determined
      frequent error types and how use of specific linguistic features varied across
      grades. RESULTS: Phonological, orthographic, and morphological errors were noted
      across all grades, but orthographic errors predominated. Linear trends revealed
      developmental shifts in error proportions for the orthographic and morphological
      categories between Grades 4 and 5. Similar error types were noted across age
      groups, but the nature of linguistic feature error changed with age. CONCLUSIONS:
      Triple word-form theory was supported. By Grade 1, orthographic errors
      predominated, and phonological and morphological error patterns were evident.
      Morphological errors increased in relative frequency in older students, probably
      due to a combination of word-formation issues and vocabulary growth. These
      patterns suggest that normal spelling development reflects nonlinear growth and
      that it takes a long time to develop a robust orthographic lexicon that
      coordinates phonology, orthography, and morphology and supports word-specific,
      conventional spelling.

PMID- 22473835
TI  - Developmental trajectory for production of prosody: lexical stress contrastivity
      in children ages 3 to 7 years and in adults.
AB  - PURPOSE: Accurate production of lexical stress within English polysyllabic words
      is critical for intelligibility and is affected in many speech-language
      disorders. However, models of speech production remain underspecified with regard
      to lexical stress. In this study, the authors report a large-scale acoustic
      investigation of lexical stress production in typically developing Australian
      English-speaking children ages 3-7 years (  n = 73) compared with young adults ( 
      n = 24). METHOD: Participants named pictures of highly familiar strong-weak and
      weak-strong polysyllabic words. Of 388 productions, 325 met criteria for acoustic
      measurement. Relative vowel duration, peak intensity, and peak   f  (0) over the
      first two syllables were measured.  Result Lexical stress was marked consistently
      by duration and intensity but not   f  (0). Lexical stress on strong-weak words
      was adultlike by 3 years. All 3 measures showed significant differences between
      adults and children for weak-strong words still present at 7 years. CONCLUSION:
      Our findings suggest that protracted development of weak-strong stress production
      reflects physiological constraints on producing short articulatory durations and
      rising intensity contours. Findings validate treatment that is centered on strong
      weak stress production for children >= 3 years with dysprosody. Although
      intervention for the production of weak-strong words may be initiated before age
      7 years, reference to normative acoustic data is preferable to relying on
      perceptual judgments of accuracy.

PMID- 22473836
TI  - Cognitive, environmental, and linguistic predictors of syntax in fragile X
      syndrome and Down syndrome.
AB  - PURPOSE: To examine which cognitive, environmental, and speech-language variables
      predict expressive syntax in boys with fragile X syndrome (FXS), boys with Down
      syndrome (DS), and typically developing (TD) boys, and whether predictive
      relationships differed by group. METHOD: We obtained Index of Productive Syntax (
      Scarborough, 1990) scores for 18 boys with FXS only, 20 boys with both FXS and
      an autism spectrum disorder, 27 boys with DS, and 25 younger TD boys of similar
      nonverbal mental age. Predictors included group (diagnosis), nonverbal cognition,
      phonological working memory (PWM), maternal education, speech intelligibility,
      and expressive vocabulary. The research questions were addressed via hierarchical
      linear regression. RESULTS: Diagnostic group, nonverbal cognition, and PWM
      predicted 56% of the variance in syntactic ability, with approximately three
      fourths of the predicted variance explained by group membership alone. The other
      factors did not contribute any additional significant variance in this final
      model. There was no evidence that predictor effects differed by group.
      CONCLUSIONS: Nonverbal cognition and PWM have an effect on expressive syntax
      beyond that of diagnostic group. These effects are estimated to be the same in
      boys with FXS, boys with DS, and TD boys. Explanations for residual variance and
      the relative role of different predictors are discussed.

PMID- 22473837
TI  - High frequency sacral root nerve block allows bladder voiding.
AB  - AIMS: Dyssynergic reflexive external urethral sphincter (EUS) activity following
      spinal cord injury can prevent bladder voiding, resulting in significant medical
      complications. Irreversible sphincterotomies or neurotomies can prevent EUS
      activation and allow bladder voiding, but may cause incontinence or loss of
      sacral reflexes. We investigated whether kilohertz frequency (KF) electrical
      conduction block of the sacral roots could prevent EUS activation and allow
      bladder voiding. METHODS: The S2 sacral nerve roots were stimulated bilaterally
      to generate bladder pressure in six cats. One S1 nerve root was stimulated
      proximally (20 Hz biphasic pulse trains) to evoke EUS pressure, simulating worst
      case dyssynergic EUS reflexes. KF waveforms (12.5 kHz biphasic square wave)
      applied to an electrode implanted distally on the S1 nerve root blocked nerve
      conduction, preventing the increase in EUS pressure and allowing voiding.
      RESULTS: Applying KF waveforms increased bladder voiding in single, limited
      duration trials from 3 +/- 6% to 59 +/- 12%. Voiding could be increased to 82 +/-
      9% of the initial bladder volume by repeating or increasing the duration of the
      trials. CONCLUSIONS: Sacral nerve block can prevent EUS activation and allow
      complete bladder voiding, potentially eliminating the need for a neurotomy.
      Eliminating neurotomy requirements could increase patient acceptance of bladder
      voiding neuroprostheses, increasing patient quality of life and reducing the cost
      of patient care.

PMID- 22473838
TI  - Serum autotaxin is increased in pruritus of cholestasis, but not of other origin,
      and responds to therapeutic interventions.
AB  - Pruritus is a seriously disabling symptom accompanying many cholestatic liver
      disorders. Recent experimental evidence implicated the lysophospholipase,
      autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential
      mediators of cholestatic pruritus. In this study, we highlight that increased
      serum ATX levels are specific for pruritus of cholestasis, but not pruritus of
      uremia, Hodgkin's disease, or atopic dermatitis. Treatment of patients with
      cholestasis with the bile salt sequestrant, colesevelam, but not placebo,
      effectively reduced total serum bile salts and fibroblast growth factor 19
      levels, but only marginally altered pruritus intensity and ATX activity.
      Rifampicin (RMP) significantly reduced itch intensity and ATX activity in
      patients with pruritus not responding to bile salt sequestrants. In vitro, RMP
      inhibited ATX expression in human HepG2 hepatoma cells and hepatoma cells
      overexpressing the pregnane X receptor (PXR), but not in hepatoma cells in which
      PXR was knocked down. Treatment of severe, refractory pruritus by the molecular
      adsorbents recirculation system or nasobiliary drainage improved itch intensity,
      which, again, correlated with the reduction of ATX levels. Upon reoccurrence of
      pruritus, ATX activity returned to pretreatment values. CONCLUSION: Serum ATX
      activity is specifically increased in patients with cholestatic, but not other
      forms of, systemic pruritus and closely correlates with the effectiveness of
      therapeutic interventions. The beneficial antipruritic action of RMP may be
      explained, at least partly, by the PXR-dependent transcriptional inhibition of
      ATX expression. Thus, ATX likely represents a novel therapeutic target for
      pruritus of cholestasis.

PMID- 22473839
TI  - Effects of lysophosphatidic acid on calpain-mediated proteolysis of focal
      adhesion kinase in human prostate cancer cells.
AB  - BACKGROUND: Calcium-mediated proteolysis plays an important role in cell
      migration. Lysophosphatidic acid (LPA), a lipid mediator present in serum,
      enhances migration of carcinoma cells. The effects of LPA on calpain-mediated
      proteolysis were, therefore, examined in PC-3, a human prostate cancer cell line.
      METHODS: Cultured PC-3 cells were used in studies utilizing pharmacologic
      interventions, immunoblotting, and confocal immunolocalization. RESULTS: Focal
      adhesion kinase (FAK), a tyrosine kinase involved in cell adhesion, is rapidly
      proteolyzed in serum-starved PC-3 cells exposed to the calcium ionophore,
      ionomycin; Nck, p130CAS, PKCalpha, and Ras-GAP are also degraded. Thapsigargin,
      which causes more moderate increases in intracellular calcium, induces partial
      proteolysis of these proteins. Calpain inhibitors block the proteolytic responses
      to ionomycin and thapsigargin. Ionomycin does not induce proteolysis in cells
      maintained in serum, suggesting a protective role for growth factors contained in
      serum. LPA causes minor FAK proteolysis when added alone, but protects against
      ionomycin-induced proteolysis in a time-dependent manner. LPA also protects
      against the cell detachment that eventually follows ionomycin treatment. The
      response to LPA is blocked by an LPA receptor antagonist. A similar effect of LPA
      is observed in ionomycin-treated Rat-1 fibroblasts. In PC-3 cells, the protective
      effects of LPA and serum are correlated with phosphorylation and redistribution
      of paxillin, suggesting roles for phosphorylation-mediated protein-protein
      interactions. CONCLUSIONS: The complex effects of LPA on calpain-mediated
      proteolysis of FAK and other adhesion proteins are likely to play a role in the
      ability of LPA to promote attachment, migration, and survival of prostate cancer
      cells.

PMID- 22473841
TI  - Synthesis of planar chiral iridacycles by cationic metal pi-coordination: facial
      selectivity, and conformational and stereochemical consequences.
AB  - Facial selectivity during the pi-coordination of pseudo-tetrahedral iridacycles
      by neutral (Cr(CO)(3)), monocationic (Cp*Ru(+)), and biscationic (Cp*Ir(2+))
      metal centers was directly influenced by the coulombic imbalance in the
      coordination sphere of the chelated Ir center. We also showed by using
      theoretical calculations that the feasibility of the related metallacycles that
      displayed metallocenic planar chirality was dependent to the presence of an
      electron-donating group, such as NMe(2), which contributed to the overall
      stability of the complexes. When the pi-bonded moiety was the strongly electron
      withdrawing Cp*Ir(2+) group, the electron donation from NMe(2) resulted in major
      conformational changes, with a barrier to rotation of about 17 kcal  mol(-1) for
      this group that became spectroscopically diastereotopic (high-field (1)H NMR
      spectroscopy). This peculiar property is proposed as a means to introduce a new
      type of constitutional chirality at the nitrogen center: planar chirality at
      tertiary aromatic amines.

PMID- 22473840
TI  - Predicting perforator location on preoperative imaging for the profunda artery
      perforator flap.
AB  - INTRODUCTION: The profunda artery perforator (PAP) flap is a new addition to our
      reconstructive armamentarium. In effort to better understand patient candidacy
      for the PAP flap we characterized the profunda artery perforators on preoperative
      imaging. METHODS: A retrospective review was completed of 40 preoperative
      posterior thigh computed tomography angiographies and magnetic resonance
      angiographies by four plastic surgeons. The positioning of the patient, type of
      study, number of perforators, and size of perforators were documented. The
      location was documented on an x-y-axis. Perforator course and surrounding
      musculature was documented. RESULTS: In 98.8% of posterior thighs suitable
      profunda artery perforators were identified. The average number and size of
      perforators was 3.3 and 1.9 mm. The most common perforator was medial (present in
      85.6% of thighs); found near the adductor magnus at 3.8 cm from midline and 5.0
      cm below the gluteal fold. The second most common perforator was lateral (present
      in 65.4% of thighs); found near the biceps femoris and vastus lateralis at 12.0
      cm from midline and 5.0 cm below the gluteal fold. Nearly 48.3% were purely
      septocutaneous. And 51.7% had an intramuscular course (average length 5.7 cm).
      Preoperative imaging corresponded to suitable perforators at the time of
      dissection of all PAP flaps. Thirty five PAP flaps (18 patients) were performed
      with 100% flap survival. CONCLUSION: Analysis of preoperative posterior thigh
      imaging confirms our intraoperative findings that a considerable number of
      suitable posterior thigh profunda perforators are present, emerge from the fascia
      in a common pattern, and are of sufficient caliber to provide adequate flap
      perfusion and recipient vessel size match.

PMID- 22473842
TI  - The importance of being exchanged: [Gd(III)4M(II)8(OH)8(L)8(O2CR)8]4+ clusters
      for magnetic refrigeration.

PMID- 22473844
TI  - Multiplicative mechanism of lateral interactions revealed by controlling
      interhemispheric input.
AB  - Long-range horizontal connections are thought to modulate the responsiveness of
      neurons by supplying contextual information. A special type of long-range
      connections are interhemispheric projections, linking the 2 cerebral hemispheres.
      To investigate the action of those projections in a causal approach, we recorded
      in cat primary visual cortex while deactivating corresponding regions on the
      contralateral hemisphere. Interestingly, the action of callosal projections
      turned out to depend on the local and global composition of the stimulus: Full
      field stimulation with gratings revealed moderate rate decreases (modulation
      index -0.24) and some significant increases (+0.21), whereas with lesser salient
      random dot textures, much more neurons were affected and reacted with pronounced
      rate decreases (-0.4). However, orientation and direction selectivity of those
      neurons were only slightly influenced by callosal input. This invariance could be
      achieved by scaling responses multiplicatively. Indeed, we could quantify the
      action of callosal input as a multiplicative scaling of responses, but additive
      scaling also occurred, especially for grating stimulation. We conclude that the
      quantitative action of long-range horizontal connections is by no means fixed but
      depends on how the network is driven by an external stimulus. Qualitatively,
      those connections seem to adjust the response gain of neurons, thereby preserving
      their selectivity.

PMID- 22473843
TI  - The brain circuitry underlying the temporal evolution of nausea in humans.
AB  - Nausea is a universal human experience. It evolves slowly over time, and brain
      mechanisms underlying this evolution are not well understood. Our functional
      magnetic resonance imaging (fMRI) approach evaluated brain activity contributing
      to and arising from increasing motion sickness. Subjects rated transitions to
      increasing nausea, produced by visually induced vection within the fMRI
      environment. We evaluated parametrically increasing brain activity 1)
      precipitating increasing nausea and 2) following transition to stronger nausea.
      All subjects demonstrated visual stimulus-associated activation (P < 0.01) in
      primary and extrastriate visual cortices. In subjects experiencing motion
      sickness, increasing phasic activity preceding nausea was found in amygdala,
      putamen, and dorsal pons/locus ceruleus. Increasing sustained response following
      increased nausea was found in a broader network including insular, anterior
      cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover,
      sustained anterior insula activation to strong nausea was correlated with
      midcingulate activation (r = 0.87), suggesting a closer linkage between these
      specific regions within the brain circuitry subserving nausea perception. Thus,
      while phasic activation in fear conditioning and noradrenergic brainstem regions
      precipitates transition to strong nausea, sustained activation following this
      transition occurs in a broader interoceptive, limbic, somatosensory, and
      cognitive network, reflecting the multiple dimensions of this aversive commonly
      occurring symptom.

PMID- 22473845
TI  - Tools for characterizing the whole-cell bio-oxidation of alkanes at microscale.
AB  - This article describes the first reported microwell whole-cell bioconversion
      using a water immiscible substrate that matches the specific activity and yield
      achieved in a 1.2 L stirred tank bioreactor. Maximum yields of 0.6 g/L(total) 1
      dodecanol achieved in 24 h compare favorably to 0.28 g/L(total) 1-dodecanol after
      48 h obtained in a stirred tank reactor. Using the microwell platform we present
      a rapid and systematic approach to identify the key bottlenecks in the bio
      oxidation of long-chain alkanes using Escherichia coli expressing the alkane
      hydroxylase (alkB) complex. The results indicate that mass transfer rates limit
      productivity in the n-dodecane bio-oxidation system, rather than inherent enzyme
      activity. Furthermore, substrate solubility, oxygen availability and glucose
      concentration act cooperatively to affect the amount of by-product, dodecanoic
      acid. Optimizing these factors using response surface methodology enabled
      specific yields of 1-dodecanol to increase eightfold and overoxidation to
      dodecanoic acid to be reduced from 95% to 55%. This resulted in specific
      activities of 10.4 umol/min/g(dcw) on n-dodecane; approximately 50% of the 21
      umol/min/g(dcw) obtained with n-octane. For the first time, this in vivo rate
      difference is within the range reported for the purified enzyme. Finally, the
      results obtained also provide strong evidence that the mechanism of E. coli
      interaction with alkanes is mainly via uptake of alkanes dissolved in the aqueous
      phase rather than by direct cell-droplet contact.

PMID- 22473846
TI  - Proteomics reviews 2012.

PMID- 22473848
TI  - Fcepsilon receptor expression in human airway smooth muscle cells.

PMID- 22473851
TI  - Determination of the anti-viral drug Ribavirin in dosage forms via micelle
      enhanced spectrofluorimetric method.
AB  - A simple and sensitive spectrofluorimetric method was developed for the
      determination of Ribavirin in pharmaceutical formulations. The proposed method
      was based on the fluorescence spectral behaviour of Ribavirin in a sodium dodecyl
      sulfate (SDS) micellar system. In an aqueous acetate buffer solution of pH 4.0,
      the fluorescence intensity of Ribavirin was significantly enhanced by about 217%
      in the presence of SDS. Fluorescence intensity was measured at 396 nm after
      excitation at 270 nm for Ribavirin. The fluorescence-concentration plot was
      rectilinear over the range of 0.01-3.0 ug/mL for Ribavirin with a lower detection
      limit of 5.02 x 10(-3) ug/mL. The method was successfully applied to the analysis
      of the drug in its commercial capsules. Results were in good agreement with those
      obtained with the official method. The application of the proposed method was
      extended to stability studies of Ribavirin after exposure to different forced
      degradation conditions such as acidic, alkaline, photo and oxidative conditions
      according to ICH guidelines.

PMID- 22473852
TI  - Lesion-induced generation of interneuron cell types in specific dorsoventral
      domains in the spinal cord of adult zebrafish.
AB  - In contrast to mammals, adult zebrafish regenerate neurons in the lesioned spinal
      cord. For example, motor neurons are generated from an olig2-expressing
      population of pMN-like ependymoradial glial cells in a ventrolateral position at
      the central canal. However, the extent of neuronal regeneration is unclear. Here
      we show, using a transgenic fish in which V2 interneurons are labeled by green
      fluorescent protein (GFP) under the control of the vsx1 promoter, that after a
      complete spinal cord transection, large numbers of V2 interneurons are generated
      in the vicinity of the lesion site. Tg(vsx1:GFP)+ cells are not present in the
      unlesioned spinal cord and label with the proliferation marker bromodeoxyuridine
      (BrdU) after a lesion. Some mediolaterally elongated Tg(vsx1:GFP)+ cells contact
      the central canal in a medial position. These cells likely arise from a p2-like
      domain of ependymoradial glial progenitor cells, indicated by coexpression of
      Pax6 and Nkx6.1, but not DsRed driven by the olig2 promoter in these cells. We
      also present evidence that Pax2+ interneurons are newly generated after a spinal
      lesion, whereas the generation rate for a dorsal population of parvalbuminergic
      interneurons is comparatively low. Our results identify the regenerative
      potential of different interneuron types for the first time and support a model
      in which different progenitor cell domains in distinct dorsoventral positions
      around the central canal are activated by a lesion to give rise to diverse
      neuronal cell types in the adult zebrafish spinal cord.

PMID- 22473853
TI  - Determination of carotenoids and their esters in fruits of sea buckthorn
      (Hippophae rhamnoides L.) by HPLC-DAD-APCI-MS.
AB  - INTRODUCTION: The berries of Hippophae rhamnoides Linnaeus have high nutritional
      and medicinal values and have been used for centuries as food both in Europe and
      Asia. The oleoresins represent a potential source of carotenoid esters and can be
      used as food additives, cosmetic ingredients or nutraceuticals. OBJECTIVE: The
      objective of this study was to develop a HPLC-DAD-APCI-MS method, with both
      positive and negative ionisation modes, for the direct identification of the
      native carotenoid composition in fruits of Hippophae rhamnoides. MATERIALS AND
      METHODS: Fruits of Hippophae rhamnoides, cv. Serbanesti and Victoria, were
      collected from an experimental field at the Fruit Research Station of Bacau,
      Romania. Samples were extracted using methanol:ethyl acetate:petroleum ether
      (1:1:1, v/v/v). The HPLC-DAD-APCI-MS analyses were carried out on a Shimadzu
      system using a YMC C30-column and a gradient elution. RESULTS: In total 22
      compounds were detected, eight were free carotenoids, nine were xanthophylls
      monoesters and five were xanthophylls diesters. Differences were observed in the
      relative percentage composition of the identified components among the two
      cultivars investigated. Zeaxanthin-C16:0,C16:0 was the most abundant diester. The
      unsaturated palmitoleic acid was directly detected in its esterified form, in
      zeaxanthin-C16:0,C16:1, which is reported here for the first time. Although
      present in small amounts the unsaturated oleic, linoleic, linolenic,
      hexadecadienoic and hexadecatrienoic acids were detected in their esterified
      forms as lutein monoesters, the last two having been detected in Hippophae
      rhamnoides for the first time. CONCLUSION: A novel (HPLC-DAD-APCI-MS) method was
      developed for the direct identification of the native carotenoid composition in
      fruits of Hippophae rhamnoides.

PMID- 22473854
TI  - Referrals for suspected hematologic malignancy: a survey of primary care
      physicians.
AB  - Little is known about referrals from primary care providers (PCPs) for suspected
      hematologic malignancies, including their clinical triggers and frequency. A
      random sample of 190 Massachusetts PCPs were presented with a vignette concerning
      a patient with a new finding of moderate anemia, asked how they would respond,
      and then asked what they would do if the patient returned with persistent anemia
      plus one additional sign or symptom. We also asked about referral behaviors for
      suspected hematologic malignancies during the prior year. A total of 134 (70.5%)
      PCPs responded. At first anemia presentation,only 3.8% reported referring to
      hematology. The development of a second sign or symptom yielded higher referral
      rates: pancytopenia 588.7%, leukopenia 5 63.9%, thrombocytopenia 5 63.9%,
      lymphadenopathy 5 42.9%, leukocytosis 5 37.6%, night sweats 5 25.6%, and weight
      loss 5 23.3%. The median yearly number (interquartile range) of patients PCPs
      reported suspecting of having hematologic malignancy was 5 (3, 10), and the
      median formally referred was 5 (3, 10). We conclude that anemia plus signs and
      symptoms suggestive of myelodysplasia or leukemia (compared with those suggestive
      of lymphoma) are more likely to prompt hematology referral. In addition, given
      their rarity,the numbe

PMID- 22473855
TI  - Efficacy of an adjunctive computer-based cognitive training program in amnestic
      mild cognitive impairment and Alzheimer's disease: a single-blind, randomized
      clinical trial.
AB  - OBJECTIVE: This study evaluates the efficacy at 12 months of a computer-based
      cognitive training (CBCT) program, adjunctive to traditional cognitive training
      (TCT), on the basis of pen-and-paper exercises. METHODS: Sixty patients with
      multi-domain mild cognitive impairment and mild Alzheimer's disease who were
      already receiving cognitive training, recruited from a day hospital, were
      assigned into two groups following a simple randomization procedure (computerized
      random numbers): (i) a group that received CBCT during 3 months and TCT (CBCT +
      TCT), n = 37, and (ii) a group that received only TCT, n = 23. Patients were
      assessed at baseline and after 3 and 12 months of treatment by a
      neuropsychologist blinded to group assignment, with a neuropsychological battery
      (primary outcomes) and measures of decision making, memory complaints, and
      emotional disturbances. RESULTS: With the use of repeated-measures analyses of
      covariance, the CBCT + TCT group showed less anxiety symptoms (F = 5.13, p =
      0.03, d = 1.12) and less disadvantageous choices (F = 4.70, p = 0.04, d = 0.89)
      in decision making than the TCT group at 12 months. No significant improvement or
      worsening was observed in the other measures examined. However, positive effect
      sizes favoring the CBCT + TCT group were observed in all variables. CONCLUSIONS:
      The addition of a CBCT program was effective in anxiety and decision making but
      had no significant effects on outcomes in basic cognitive functions in patients
      who were already receiving cognitive training, possibly due to a ceiling effect.
      Future studies should compare the efficacy of CBCT with TCT in naive patients.

PMID- 22473856
TI  - ATP-binding cassette (ABC) transporter expression and localization in sea urchin
      development.
AB  - BACKGROUND: ATP-binding cassette (ABC) transporters are membrane proteins that
      regulate intracellular concentrations of myriad compounds and ions. There are
      >100 ABC transporter predictions in the Strongylocentrotus purpuratus genome,
      including 40 annotated ABCB, ABCC, and ABCG "multidrug efflux" transporters.
      Despite the importance of multidrug transporters for protection and signaling,
      their expression patterns have not been characterized in deuterostome embryos.
      RESULTS: Sea urchin embryos expressed 20 ABCB, ABCC, and ABCG transporter genes
      in the first 58 hr of development, from unfertilized egg to early prism. We
      quantified transcripts of ABCB1a, ABCB4a, ABCC1, ABCC5a, ABCC9a, and ABCG2b, and
      found that ABCB1a mRNA was 10-100 times more abundant than other transporter
      mRNAs. In situ hybridization showed ABCB1a was expressed ubiquitously in embryos,
      while ABCC5a was restricted to secondary mesenchyme cells and their precursors.
      Fluorescent protein fusions showed localization of ABCB1a on apical cell
      surfaces, and ABCC5a on basolateral surfaces. CONCLUSIONS: Embryos use many ABC
      transporters with predicted functions in cell signaling, lysosomal and
      mitochondrial homeostasis, potassium channel regulation, pigmentation, and
      xenobiotic efflux. Detailed characterization of ABCB1a and ABCC5a revealed that
      they have different temporal and spatial gene expression profiles and protein
      localization patterns that correlate to their predicted functions in protection
      and development, respectively.

PMID- 22473857
TI  - The monoamine oxidase A gene promoter repeat and prostate cancer risk.
AB  - BACKGROUND: Amine catabolism by monoamine oxidase A (MAOA) contributes to
      oxidative stress, which plays a role in prostate cancer (PCa) development and
      progression. An upstream variable-number tandem repeat (uVNTR) in the MAOA
      promoter influences gene expression and activity, and may thereby affect PCa
      susceptibility. METHODS: Caucasian (n = 2,572) men from two population-based case
      control studies of PCa were genotyped for the MAOA-VNTR. Logistic regression was
      used to assess PCa risk in relation to genotype. RESULTS: Common alleles of the
      MAOA-VNTR were not associated with the relative risk of PCa, nor did the
      relationship differ by clinical features of the disease. The rare 5-copy variant
      (frequency: 0.5% in cases; 1.8% in controls), however, was associated with a
      reduced PCa risk (odds ratio, OR = 0.30, 95% CI 0.13-0.71). CONCLUSIONS: A rare
      polymorphism of the MAOA promoter previously shown to confer low expression was
      associated with a reduced risk of developing PCa. This novel finding awaits
      confirmation in other study populations.

PMID- 22473858
TI  - IL28B polymorphisms predict interferon-related hepatitis B surface antigen
      seroclearance in genotype D hepatitis B e antigen-negative patients with chronic
      hepatitis B.
AB  - Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)
      induced viral clearance in patients with chronic hepatitis C. Whether this is
      also true for patients with the difficult-to-cure hepatitis B e antigen (HBeAg)
      negative chronic hepatitis B (CHB) is unknown. One hundred and one HBeAg-negative
      patients (92% genotype D) with compensated CHB (84% males, 46 years; hepatitis B
      virus [HBV] DNA: 6.0 log cp/mL; alanine aminotransferase [ALT]: 136 IU/L; 42%
      with cirrhosis) were followed up for a median of 11 years (range, 1-17) after a
      median of 23 months (range, 10-48) of either standard or pegylated (Peg)-IFN
      alpha therapy. A post-treatment response was defined as hepatitis B surface
      antigen (HBsAg) clearance with or without antibody to hepatitis B surface antigen
      (anti-HBs) seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was
      assessed in serum samples by using Custom TaqMan SNP Genotyping Assays (Applied
      Biosystems, Carlsbad, CA). During a median of 11 years of post-treatment follow
      up, 21 patients (21%) cleared serum HBsAg, including 15 who developed>10 IU/mL of
      anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) had CT, and
      11 (11%) had TT, with the allelic frequency being 68% for C allele and 32% for T
      allele. The rate of serum HBsAg clearance was 29% (n=14) in CC compared to 13%
      (n=7) in non-CC, genotype carriers (P=0.039). Baseline HBV DNA levels<6 log cp/mL
      (odds ratio [OR], 11.9; 95% confidence interval [CI]: 2.8-50.6; P=0.001), ALT
      levels>136 IU/L (OR, 6.5; 95% CI: 1.8-22.5; P=0.003), duration of IFN (OR, 1.16;
      95% CI: 1.02-1.31; P=0.021), and genotype CC (OR, 3.9; 95% CI: 1.1-13.2; P=0.025)
      independently predicted HBsAg clearance. CONCLUSIONS: IL28B polymorphism is an
      additional predictor of off-therapy IFN-related HBsAg seroclearance to be used in
      the pretreatment stratification of HBeAg-negative patients chronically infected
      by genotype D of HBV.

PMID- 22473859
TI  - Free transverse rectus abdominis myocutaneous flap reconstruction of a massive
      lumbosacral defect using superior gluteal artery perforator vessels.
AB  - Despite significant advances in reconstructive surgery, the repair of massive
      lumbosacral defects poses significant challenges. When the extent of soft tissue
      loss, tumor resection, and/or radiation therapy preclude the use of traditional
      local options, such as gluteal advancement flaps or pedicled thigh flaps, then
      distant flaps are required. We report a case of a 64-year-old male who presented
      with a large sacral Marjolin's ulcer secondary to recurrent pilonidal cysts and
      ulcerations. The patient underwent wide local composite resection, which resulted
      in a wound measuring 450 cm(2) with exposed rectum and sacrum. The massive defect
      was successfully covered with a free transverse rectus abdominis myocutaneous
      flap, providing a well-vascularized skin paddle and obviating the need for a
      latissimus flap with skin graft. The free-TRAM flap proved to be a very robust
      flap in this situation and would be one of our flaps of choice for similar
      defects.

PMID- 22473860
TI  - Expanding the chemistry of cationic N-heterocyclic carbenes: alternative
      synthesis, reactivity, and coordination chemistry.
AB  - A new synthetic route to complexes of the cationic N-heterocyclic carbene ligand
      2 has been developed by the attachment of a cationic
      pentamethylcyclopentadienylruthenium ([RuCp*](+)) fragment to a metal-coordinated
      benzimidazol-2-ylidene ligand. The coordination chemistry and the steric and
      electronic properties of the cationic carbene were investigated in detail by
      experimental and theoretical methods. X-ray structures of three carbene-metal
      complexes were determined. The cationic ligand 2 is a poorer overall electron
      donor relative to the related neutral carbene, which is evident from cyclic
      voltammetry (CV) and IR measurements.

PMID- 22473861
TI  - Structure-based macrocyclization yields hepatitis C virus NS5B inhibitors with
      improved binding affinities and pharmacokinetic properties.

PMID- 22473862
TI  - Management of left ventricular distension during peripheral extracorporeal
      membrane oxygenation for cardiogenic shock.
AB  - The application of peripheral veno-arterial extracorporeal membrane oxygenation
      in the management of inotrope-refractory cardiogenic shock has proven
      controversial because of concerns about sub-optimal drainage of the left heart,
      resulting in left ventricular distension and pulmonary oedema. In this article,
      we will discuss the pathophysiological basis and clinical implications of left
      ventricular distension following institution of peripheral extracorporeal life
      support. We will also review the clinical strategies used to circumvent left
      ventricular distension and pulmonary oedema in these patients.

PMID- 22473863
TI  - Nicorandil ameliorates hypertension-related bladder dysfunction in the rat.
AB  - AIMS: There is increasing evidence that ischemia is one of the main etiology in
      overactive bladder (OAB), and that nicorandil prevents OAB. We investigated the
      effect of nicorandil on hypertension-related bladder dysfunction in spontaneously
      hypertensive rats (SHRs). METHODS: Twelve-week-old SHRs received six-weeks
      treatment with nicorandil (0, 3, or 10 mg/kg, i.p. every day). Wistar rats were
      used for normotensive controls. Six weeks after nicorandil treatment, the bladder
      blood flow was estimated by hydrogen clearance method, and the bladder functions
      were estimated by voiding behavior studies and functional studies. Tissue levels
      of nerve growth factor (NGF) were measured by ELISA method. Furthermore, the
      participation levels of K(ATP) channel pores were investigated by real-time PCR.
      RESULTS: SHRs showed significant increases in blood pressure, micturition
      frequency, tissue levels of NGF and expressions of both K(IR) 6.1 and K(IR) 6.2
      mRNAs, and a significant decrease in the bladder blood flow. The carbachol
      induced contractile responses were similar in all groups. Although both doses of
      nicorandil failed to decrease the blood pressure, nicorandil significantly
      decreased the micturition frequency, tissue levels of NGF and increased the
      bladder blood flow in a dose dependent manner. The expressions of K(IR) 6.1 and
      K(IR) 6.2 mRNAs were slightly up-regulated by the low dose of nicorandil, whereas
      the high dose of nicorandil significantly up-regulated those expressions compared
      to non-treated SHRs. CONCLUSIONS: These data indicate that nicorandil prevents
      hypertension-related bladder dysfunction in the SHR, which may be related to its
      effect on the increased blood flow in the bladder.

PMID- 22473864
TI  - Perceived social acceptance and peer status differentially predict adjustment in
      youth with and without ADHD.
AB  - OBJECTIVE: This study extends previous research and examined if the longitudinal
      relation between self-perceived social acceptance and changes in adjustment was
      moderated by peer status and ADHD diagnosis. METHOD: A sample of children with
      ADHD and a normative comparison group (age 8-13 years) were assessed at baseline
      and one-year follow-up. Self-perceived social acceptance, peer status, and three
      areas of adjustment (depression symptoms, aggression/conduct problems, and social
      skills) were measured. RESULTS: Moderation was found when predicting depression
      symptoms and aggression/conduct problems. Specifically, in children with ADHD
      only, higher perceived social acceptance protected against increases in
      depression symptoms for those with lower peer preference, but predicted greater
      aggression/conduct problems for those with higher peer preference. There was not
      evidence of significant moderation for predicting social skills; instead non-ADHD
      status, greater peer preference, and greater self-perceived social acceptance
      were each predictive of greater social skills. CONCLUSION: Results highlight the
      complex association between positive social self-perceptions and adjustment for
      children with ADHD and caution against a universal assumption that high self
      perceptions are adaptive.

PMID- 22473865
TI  - Isolation and expression of genes for acetolactate synthase and acetyl-CoA
      carboxylase in Echinochloa phyllopogon, a polyploid weed species.
AB  - BACKGROUND: Target-site resistance is the major cause of herbicide resistance to
      acetolactate synthase (ALS)- and acetyl-CoA carboxylase (ACCase)-inhibiting
      herbicides in arable weeds, whereas non-target-site resistance is rarely
      reported. In the Echinochloa phyllopogon biotypes resistant to these herbicides,
      target-site resistance has not been reported, and non-target-site resistance is
      assumed to be the basis for resistance. To explore why target-site resistance had
      not occurred, the target-site genes for these herbicides were isolated from E.
      phyllopogon, and their expression levels in a resistant biotype were determined.
      RESULTS: Two complete ALS genes and the carboxyltransferase domain of four ACCase
      genes were isolated. The expression levels of ALS and ACCase genes were higher in
      organs containing metabolically active meristems, except for ACC4, which was not
      expressed in any organ. The differential expression among examined organs was
      more prominent for ALS2 and ACC2 and less evident for ALS1, ACC1 and ACC3.
      CONCLUSION: E. phyllopogon has multiple copies of the ALS and ACCase genes, and
      different expression patterns were observed among the copies. The existence of
      three active ACCase genes and the difference in their relative expression levels
      could influence the occurrence of target-site resistance to ACCase inhibitors in
      E. phyllopogon.

PMID- 22473868
TI  - Biphasic wnt8a expression is achieved through interactions of multiple regulatory
      inputs.
AB  - BACKGROUND: Vertebrate axis development depends upon wnt8a transcription in a
      dynamic pool of mesoderm progenitors at the posterior pole of the gastrulating
      embryo. The transcriptional mechanisms controlling wnt8a expression are not
      understood, but previous studies identified two phases of wnt8a expression in
      zebrafish: Nodal-dependent activation during early gastrulation (phase I) and No
      tail (Ntl)-dependent regulation from mid gastrula stages (phase II). RESULTS: We
      identified two upstream cis-regulatory regions, proximal and distal, each of
      which possesses a promoter. The proximal regulatory region contains a margin
      specific enhancer that is required for both the Nodal and Ntl responses. Phase I
      expression requires Nodal activation of the margin enhancer in combination with
      the transcription factor Zbtb4 and the distal regulatory region. Phase II
      expression requires Ntl regulation of the margin enhancer in the context of the
      proximal regulatory region. An additional mechanism is required to ensure the
      transition from phase I to phase II regulation. Analysis of stickleback wnt8a
      suggests this mechanism of regulation may be conserved. CONCLUSIONS: The
      seemingly simple wnt8a expression pattern reflects complex interactions of
      multiple regulatory inputs.

PMID- 22473867
TI  - Myelodysplastic syndrome after allogeneic hematopoietic stem cell
      transplantation: diagnostic and therapeutic challenges.

PMID- 22473869
TI  - Cochrane review on 'Statins for the treatment of dementia'.
AB  - OBJECTIVES: This review aimed to assess the clinical efficacy and tolerability of
      statins in the treatment of dementia. METHODS: We searched the Specialized
      Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane
      Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials
      registries and grey literature sources (27 October 2008). Double-blind,
      randomized controlled trials of statins given for at least 6 months in people
      with a diagnosis of dementia were included. Two independent authors extracted and
      assessed data independently against the inclusion criteria. Data were pooled
      where appropriate and entered into a meta-analysis. RESULTS: Three studies were
      identified (748 participants, age range 50-90 years). All patients had a
      diagnosis of probable or possible Alzheimer's disease according to standard
      criteria, and most patients were established on a cholinesterase inhibitor.
      Change in Alzheimer's Disease Assessment Scale cognitive subscale from baseline
      was a primary outcome in three studies; when data were pooled, statins did not
      provide any beneficial effect in this cognitive measure (mean difference -1.12;
      95% confidence interval -3.99, 1.75; p = 0.44). All studies provided a change in
      Mini-Mental State Examination from baseline; there was no significant benefit
      from statins in this cognitive measure when the data were pooled (mean difference
      -1.53; 95% confidence interval -3.28; 0.21, p = 0.08). There were no studies
      identified assessing the role of statins in treatment of vascular dementia. There
      was no evidence that statins were detrimental to cognition. CONCLUSIONS: There is
      insufficient evidence to recommend statins for the treatment of dementia.

PMID- 22473870
TI  - Contribution of genetic variants to pain susceptibility in Parkinson disease.
AB  - BACKGROUND: Pain is a one of the most disturbing non-motor symptoms of Parkinson
      disease (PD). The susceptibility to pain varies substantially among patients with
      PD. The aim of this study was to assess a potential association of genetic
      variants to PD-related pain. METHODS: We analysed 20 candidate SNPs from 12 genes
      previously reported to be associated with various pain phenotypes in a
      homogeneous group of 229 Israeli Jewish PD patients, with and without pain (n =
      165 and 64, respectively). RESULTS: The statistical analysis accounted for the
      potential influence of demographic and clinical factors. The non-synonymous
      rs6746030 single nucleotide polymorphism (SNP) of the SCN9A gene, which alters
      the coding sequence of the sodium channel Nav1.7 (arginine to tryptophan), was
      nominally associated with PD-related pain susceptibility (p = 0.037), as well as
      with central and musculoskeletal pain subtypes independently. The synonymous
      rs324419 SNP of the FAAH gene which encodes fatty acid amide hydrolase, a
      cannabinoid metabolizing enzyme, was associated with PD-related pain (p = 0.006)
      and specifically with the musculoskeletal subtype. The FAAH haplotype of rs324419
      and rs2295633 SNPs, which was previously associated with the variability in pain
      response in humans, was also associated with PD-related pain (p = 0.012) and
      specifically with PD-related musculoskeletal pain. CONCLUSIONS: Variants within
      in the SCN9A and FAAH genes were associated with the risk of pain in PD patients.
      These findings may contribute to our understanding of pain mechanisms of PD and
      to direct future therapies.

PMID- 22473871
TI  - Quantitation of alpha-galactosides in Rehmannia glutinosa by hydrophilic
      interaction chromatography-evaporative light scattering detector.
AB  - INTRODUCTION: The use of raffinose family oligosaccharides (RFOs) to control
      several diseases and stimulate immune systems has been studied. Rehmannia
      glutinosa is reported to contain RFOs; however, there are no reports on their
      content level in R. glutinosa. Furthermore, it is difficult to analyse RFOs using
      common reverse-phase chromatographic techniques due to their high polarity.
      OBJECTIVE: To develop a rapid and reliable chromatographic method for the
      simultaneous quantitation of multiple RFOs in R. glutinosa. METHODOLOGY:
      Chromatographic separation was performed by using hydrophilic interaction liquid
      chromatography coupled with an evaporative light scattering detector. For
      efficient ultrasound-assisted extraction of oligosaccharides, a central composite
      design was used. RESULTS: Response surface analysis estimated the highest
      obtained yields of raffinose, stachyose and verbascose to be 58.31, 408.75 and
      26.59 mg, respectively, from 1 g of R. glutinosa, while under optimal conditions,
      experimental yields per gram were 56.79, 391.42 and 27.69 mg, respectively.
      CONCLUSION: A rapid and reliable chromatographic method to simultaneously
      quantitate multiple RFOs in R. glutinosa was developed. Three RFOs in R.
      glutinosa were separated within 10 min using isocratic conditions. Quantitative
      analysis of RFOs showed that R. glutinosa may be a rich source of alpha-galacto
      oligosaccharides, especially stachyose.

PMID- 22473872
TI  - Effect of the anticonvulsant medications pregabalin and lamotrigine on urodynamic
      parameters in an animal model of neurogenic detrusor overactivity.
AB  - AIMS: To assess the effects of different doses and treatment durations of
      pregabalin and lamotrigine on the urodynamic parameters of an animal model of
      neurogenic detrusor overactivity (NDO). MATERIALS AND METHODS: Ninety rats were
      used; six as normal controls and the remaining 84 were divided as follows: Six
      "paraplegic controls," 6 "paraplegic-vehicle controls," and the remaining 72
      divided into two equal groups. Group 1 was divided into six subgroups; pregabalin
      was given in doses of 10 mg/kg, 20 mg/kg, or 30 mg/kg for 1 or 2 weeks. Group 2
      was similarly subdivided; lamotrigine was given in doses of 1.5 mg/kg, 3 mg/kg,
      or 6 mg/kg for 1 or 2 weeks. RESULTS: All paraplegic controls developed NDO
      within 3 weeks from spinalization. Their baseline bladder pressure (BBP) 19 +/-
      4.4 cmH(2) O, detrusor pressure at maximum capacity (DPMaxC) 47.6 +/- 4.3 cmH(2)
      O, bladder capacity (BC) 0.45 +/- 0.1 ml, and frequency of detrusor overactivity
      (FDO) 3.7 +/- 0.9/min. Both pregabalin and lamotrigine produced significant
      improvement. Urodynamic values in those treated with 20 mg pregabalin for 1 or 2
      weeks were: BBP 11.7 +/- 1.3 and 9 +/- 0.2 cmH(2) O, BC 0.6 +/- 0.1 and 0.7 +/-
      0.01 ml, DPMaxC 17.3 +/- 4.0 and 23 +/- 2.6 cmH(2) O, FDO 2.1 +/- 0.2/min and 1.7
      +/- 0.1/min. Urodynamic values in those treated with 3 mg/kg lamotrigine for 1 or
      2 weeks were: BBP 9.7 +/- 2.2 and 8.6 +/- 1.9 cmH(2) O, DPMaxC 17.2 +/- 1.8 and
      29 +/- 1.2 cmH(2) O, BC 0.7 +/- 0.1 and 0.8 +/- 0.1 ml, FDO 1.9 +/- 0.2/min and
      1.9 +/- 0.2/min (P < 0.001). CONCLUSIONS: Pregabalin and lamotrigine may
      represent novel alternative treatments of NDO. Clinical trials remain to be
      performed.

PMID- 22473873
TI  - Small molecule tolfenamic acid inhibits PC-3 cell proliferation and invasion in
      vitro, and tumor growth in orthotopic mouse model for prostate cancer.
AB  - BACKGROUND: Specificity protein (Sp) transcription factors are implicated in
      critical cellular and molecular processes associated with cancer that impact
      tumor growth and metastasis. The non-steroidal anti-inflammatory drug, tolfenamic
      acid (TA) is known to inhibit Sp proteins in some human cancer cells and
      laboratory animal models. We evaluated the anti-cancer activity of TA using in
      vitro and in vivo models for prostate cancer. METHODS: The anti-proliferative
      efficacy of TA was evaluated using DU-145, PC-3, and LNCaP cells. PC-3 cells were
      treated with DMSO or 50 uM TA for 48 hr. Whole cell lysates were evaluated for
      the expression of Sp1, survivin, c-PARP, Akt/p-Akt, c-Met, cdk4, cdc2, cyclin D3,
      and E2F1 by Western blot analysis. Cell invasion was assessed by Boyden-chamber
      assay and flow cytometry analysis was used to study apoptosis and cell cycle
      distribution. An orthotopic mouse model for prostate cancer with PC-3-Luc cells
      was used to study the in vivo effect of TA. RESULTS: TA inhibited the expression
      of Sp1, c-Met, p-Akt, and survivin; increased c-PARP expression and caspases
      activity in PC-3 cells. TA caused cell arrest at G(0) /G(1) phase accompanied by
      a decrease in cdk4, cdc2, cyclin D3, and E2F1 and an increase in critical
      apoptotic markers. TA augmented annexin-V staining, caspase activity, and c-PARP
      expression indicating the activation of apoptotic pathways. TA also decreased PC
      3 cell invasion. TA significantly decreased the tumor weight and volume which was
      associated with low expression of Sp1 and survivin in tumor sections. CONCLUSION:
      TA targets critical pathways associated with tumorigenesis and invasion. These
      pre-clinical data strongly demonstrated the anti-cancer activity of TA in
      prostate cancer.

PMID- 22473875
TI  - Rho-inhibition by local application of c3-toxin for enhancement of axonal
      sprouting in a rat end-to-side nerve repair model: a complementary mechanism.

PMID- 22473874
TI  - A myelin gene causative of a catatonia-depression syndrome upon aging.
AB  - Severe mental illnesses have been linked to white matter abnormalities,
      documented by postmortem studies. However, cause and effect have remained
      difficult to distinguish. CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) is
      among the oligodendrocyte/myelin-associated genes most robustly reduced on mRNA
      and protein level in brains of schizophrenic, bipolar or major depressive
      patients. This suggests that CNP reduction might be critical for a more general
      disease process and not restricted to a single diagnostic category. We show here
      that reduced expression of CNP is the primary cause of a distinct behavioural
      phenotype, seen only upon aging as an additional 'pro-inflammatory hit'. This
      phenotype is strikingly similar in Cnp heterozygous mice and patients with mental
      disease carrying the AA genotype at CNP SNP rs2070106. The characteristic
      features in both species with their partial CNP 'loss-of-function' genotype are
      best described as 'catatonia-depression' syndrome. As a consequence of perturbed
      CNP expression, mice show secondary low-grade inflammation/neurodegeneration.
      Analogously, in man, diffusion tensor imaging points to axonal loss in the
      frontal corpus callosum. To conclude, subtle white matter abnormalities inducing
      neurodegenerative changes can cause/amplify psychiatric diseases.

PMID- 22473876
TI  - Controlled bimodal molecular-weight-distribution polymers: facile synthesis by
      RAFT polymerization.
AB  - The RAFT agents RAFT-1 and RAFT-2 were used for RAFT polymerization to synthesize
      well-defined bimodal molecular-weight-distribution (MWD) polymers. The system
      showed excellent controllability and "living" characteristics toward both the
      higher- and lower-molecular-weight fractions. It is important that bimodal higher
      molecular-weight (HMW) polymers and block copolymers with both well-controlled
      molecular weight (MW) and MWD could be prepared easily due to the "living"
      features of RAFT polymerization. The strategy realized a mixture of higher/lower
      molecular-weight polymers at the molecular level but also preserved the features
      of living radical polymerization (LRP) of the RAFT polymerization.

PMID- 22473877
TI  - Differentiation of intrahepatic peribiliary glands and pancreatic acinar cells
      from the remodeling ductal plate in human fetuses.

PMID- 22473878
TI  - Blood component support in acquired coagulopathic conditions: is there a method
      to the madness?
AB  - Acquired coagulopathies are often detected by laboratory investigation in
      clinical practice. There is a poor correlation between mild to moderate
      abnormalities of laboratory test and bleeding tendency. Patients who are bleeding
      due to coagulopathy are often managed with various blood components including
      plasma, platelets, and cryoprecipitate. However, prophylactic transfusion of
      these products in a nonbleeding patient to correct mild to moderate abnormality
      of a coagulation test especially preprocedure is not evidence-based. This article
      reviews the management of bleeding due to oral anticoagulants and antiplatelet
      agents, disseminated intravascular coagulation, chronic liver disease, and
      trauma.

PMID- 22473879
TI  - Phosphorus as a Lewis acid: CO2 sequestration with amidophosphoranes.

PMID- 22473880
TI  - Radical activation of Si-H bonds by organozinc and silylzinc reagents: synthesis
      of geminal dizinciosilanes and zinciolithiosilanes.

PMID- 22473881
TI  - Quantifying amyloid beta (Abeta)-mediated changes in neuronal morphology in
      primary cultures: implications for phenotypic screening.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting
      millions of people. The amyloid hypothesis suggests that the pathogenesis of AD
      is related to the accumulation of amyloid beta (Abeta) in the brain. Herein, the
      authors quantify Abeta-mediated changes in neuronal morphology in primary
      cultures using the Cellomics neuronal profiling version 3.5 (NPv3.5)
      BioApplication. We observed that Abeta caused a 33% decrease in neurite length in
      primary human cortical cultures after 24 h of treatment compared with control
      treated cultures. We also determined that quantifying changes of neuronal
      morphology was a more sensitive indicator of nonlethal cell injury than
      traditional cytotoxicity assays. Abeta-mediated neuronal deficits observed in
      human cortical cultures were also observed in primary rat hippocampal cultures,
      where we demonstrated that the integrin-blocking antibody, 17E6, completely
      abrogated Abeta-mediated cytotoxicity. Finally, we showed that Abeta challenge to
      21 days in vitro rat hippocampal cultures reduced synapsin staining to 14% of
      control-treated cultures. These results are consistent with the finding that loss
      of presynaptic integrity is one of the initial deficits observed in AD. The
      implementation of phenotypic screens to identify compounds that block Abeta
      mediated cytotoxicity in primary neuronal cultures may lead to the development of
      novel strategies to prevent AD.

PMID- 22473883
TI  - Presentations and outcomes of children with intraventricular hemorrhages after
      blunt head trauma.
AB  - OBJECTIVE: To describe the clinical presentations and outcomes of children with
      intraventricular hemorrhages (IVHs) after blunt head trauma (BHT). DESIGN:
      Subanalysis of a large, prospective, observational cohort study performed from
      June 1, 2004, through September 31, 2006. SETTING: Twenty-five emergency
      departments participating in the Pediatric Emergency Care Applied Research
      Network. Patients Children presenting with IVH after BHT. Exposure Blunt head
      trauma. MAIN OUTCOME MEASURES: Clinical presentations and outcomes, including the
      Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance
      Category (PCPC) scores at hospital discharge. RESULTS: Of 15 907 patients
      evaluated with computed tomography, 1156 (7.3%) had intracranial injuries. Forty
      three of the 1156 (3.7%; 95% CI, 2.7%-5.0%) had nonisolated IVHs (ie, with
      intracranial injuries on computed tomography), and 10 of 1156 (0.9%; 95% CI, 0.4%
      1.6%) had isolated IVHs. Only 4 of 43 (9.3%) of those with nonisolated IVHs had
      Glasgow Coma Scale (GCS) scores of 14 to 15, and all 10 (100.0%) with isolated
      IVHs had GCS scores of 15. No patients with isolated IVHs required neurosurgery
      or died. One patient had moderate overall disability (by the POPC score), and no
      patient had moderate or severe disability at discharge (by the PCPC score). Of
      the 43 patients with nonisolated IVHs, however, 16 (37.2%) died and 18 (41.9%)
      required neurosurgery. In 27 patients (62.8%), injuries ranged from moderate
      overall disability to brain death by the POPC score. CONCLUSIONS: Children with
      nonisolated IVHs after BHT typically present with GCS scores of less than 14,
      frequently require neurosurgery, and have high mortality rates. In contrast,
      those with isolated IVHs typically present with normal mental status and are at
      low risk for acute adverse events and poor outcomes.

PMID- 22473882
TI  - Prospective multicenter study of viral etiology and hospital length of stay in
      children with severe bronchiolitis.
AB  - OBJECTIVE: To determine whether hospital length of stay(LOS) for acute
      bronchiolitis is influenced by the infecting pathogen. DESIGN: A prospective
      observational cohort study was performed during 3 consecutive years. SETTING:
      Sixteen US hospitals participated in the study. PARTICIPANTS: Children younger
      than 2 years hospitalized with bronchiolitis were included. MAIN EXPOSURE: The
      results of nasopharyngeal aspirate polymerase chain reaction pathogen testing
      served as the main exposure. MAIN OUTCOME MEASURE: Hospital LOS was determined.
      RESULTS: Of 2207 participants, 72.0% had respiratory syncytial virus (RSV) and
      25.6% had human rhinovirus(HRV); the incidence of each of the other viruses and
      bacteria was 7.8% or less. Multiple pathogen infections were present in 29.8% of
      the children. There were 1866 children(84.5%) with RSV and/or HRV. Among these
      1866 children, the median age was 4 months and 59.5% were male. The median LOS
      was 2 days (interquartile range,1-4 days). Compared with children who had only
      RSV,an LOS of 3 or more days was less likely among children with HRV alone
      (adjusted odds ratio [AOR], 0.36; 95%CI, 0.20-0.63; P.001) and those with HRV
      plus non-RSV pathogens (AOR, 0.39; 95% CI, 0.23-0.66; P.001)but more likely among
      children with RSV plus HRV(AOR,1.33; 95% CI, 1.02-1.73; P=.04), controlling for
      15 demographic and clinical factors. CONCLUSIONS: In this multicenter study of
      children hospitalized with bronchiolitis, RSV was the most common virus detected,
      but HRV was detected in one-quarter of the children. Since 1 in 3 children had
      multiple virus infections and HRV was associated with LOS, these data challenge
      the effectiveness of current RSV-based cohorting practices, the sporadic testing
      for HRV in bronchiolitis research, and current thinking that the infectious
      etiology of severe bronchiolitis does not affect short-term outcomes.

PMID- 22473884
TI  - Role of waist measures in characterizing the lipid and blood pressure assessment
      of adolescents classified by body mass index.
AB  - OBJECTIVE: To determine if the interaction of waist circumference percentile and
      waist to height ratio(WHtR) with body mass index (BMI) may serve to provide
      further risk specification in the lipid and blood pressure assessment of
      adolescents beyond BMI classification. DESIGN: Population-based, cross-sectional
      study. Data collected during the 2009-2010 academic school year. SETTING:
      Geographically and administratively defined Niagara Region, Ontario, Canada. Data
      collected in school, during subjects' mandatory physical education class. Part of
      the Heart Niagara Inc Healthy Heart Schools' Program. PARTICIPANTS: Entire
      population of grade 9 (14- and 15-year-old) students in the Niagara Region,
      Ontario.Four thousand eight hundred eighty-four students enrolled in grade 9
      during the study period, of which 4104 participated (51% male) and 3248 (79%) had
      complete data. MAIN OUTCOME MEASURES: Nonfasting lipid values and blood pressure
      categories in subjects categorized based on BMI/waist circumference percentile
      and BMI/WHtR. RESULTS: The associations between blood pressure, lipid profile,
      and measures of adiposity (BMI alone, BMI/waist circumference percentile, and
      BMI/WHtR) were statistically significant but had a limited strength and were not
      statistically significant from each other. For overweight and obese subjects,
      increased WHtR categories were associated with worsened lipid profile and
      increased odds of hypertension both relative to subjects with both normal BMI and
      normal WHtR and subjects with normal WHtR within each BMI category. CONCLUSION:
      Waist measures should be included in the screening and assessment of overweight
      and obese adolescents.

PMID- 22473885
TI  - Frequency of parent-supervised outdoor play of US preschool-aged children.
AB  - OBJECTIVE: To characterize preschoolers' daily parent-supervised outdoor play
      frequency and associated factors. DESIGN: Cross-sectional using data from the
      Early Childhood Longitudinal Study-Birth Cohort. SETTING: Nationally
      representative US sample. PARTICIPANTS: Preschool-aged children. MAIN OUTCOME
      MEASURE: Parent-reported outdoor play frequency. RESULTS: The sample size of 8950
      represented approximately 4 million children. Sixty percent of mothers worked
      outside the home, 79% exercised 0 to 3 days per week, and 93% perceived their
      neighborhood to be safe. Forty-four percent of mothers and 24% of fathers
      reported taking their child outside to play at least once per day. Fifty-one
      percent of children were reported to go outside to play at least once per day
      with either parent. Fifty-eight percent of children who were not in child care
      went outside daily. A child's odds of going outside daily were associated with
      sex (odds ratio [OR] for girls, 0.85;95% CI, 0.75-0.95), having more regular
      playmates (OR for >= 3 playmates, 2.03; 95% CI, 1.72-2.38), mother's
      race/ethnicity (OR for Asian, 0.51, 95% CI, 0.43-0.61; black,0.59, 95% CI, 0.49
      0.70; Hispanic, 0.80, 95% CI, 0.67-0.95), mother's employment (OR for full time,
      0.70; 95%CI, 0.62-0.81), and parent's exercise frequency of 4 days or more per
      week (OR, 1.50; 95% CI, 1.28-1.75). We did not find significant association of
      outdoor play with child's time spent watching television, household income,
      mother's marital status, or parent's perceptions of neighborhood safety.
      CONCLUSIONS: About half the preschoolers in this sample did not have even 1
      parent-supervised outdoor play opportunity per day. Efforts to increase active
      outdoor play should especially target children who are girls and nonwhite.
      Outdoor play opportunities at child care are critical for children of parents who
      work outside the home.

PMID- 22473886
TI  - Expanding the envelope of care.

PMID- 22473887
TI  - Patterns of care at end of life in children with advanced heart disease.
AB  - OBJECTIVE: To describe patterns of care for pediatric patients with advanced
      heart disease who experience in-hospital death. DESIGN: Retrospective single
      institution medical record review. SETTING: A tertiary care pediatric hospital.
      PARTICIPANTS: All patients younger than 21 years who died in the inpatient
      setting between January 1, 2007, and December 31, 2009, with primary cardiac
      diagnoses or who had ever received a cardiology consult (N=468). After excluding
      patients with significant noncardiac primary diagnoses, 111 children formed the
      analytic sample. MAIN OUTCOME MEASURE: In-hospital deaths of children with heart
      disease during a 3-year period. RESULTS: Median age at death was 4.8 months (age
      range,1 day to 20.5 years), with 84 deaths (75.7%) occurring before age 1 year.
      Median length of terminal hospital stay was 22 days (range, 1-199 days).
      Diagnoses included 84 patients (75.7%) with congenital heart disease, 10
      (9.0%)with cardiomyopathy/myocarditis, 9 (8.1%) with pulmonary hypertension, and
      8 (7.2%) with heart transplants.Sixty-two patients (55.9%) had received cardio
      pulmonary resuscitation during their last hospital admission. At the end of life,
      21 children (18.9%) had gastrostomy tubes and 26 (23.4%) had peritoneal
      drains.Most patients (91.9%) received ventilation, with half also receiving
      mechanical circulatory support. Eighty-three patients (74.8%) experienced
      additional end-organ failure. Classified by mode of death, 76 patients (68.5%)
      had disease-directed support withdrawn, 28 (25.2%) died during resuscitation, and
      7 (6.3%) died while receiving comfort care after birth. Eighty-three percent of
      parents were present at the time of death. CONCLUSION: Infants and children who
      die of advanced heart disease frequently succumb in the intensive care setting
      with multisystem organ failure and exposure to highly technical care.

PMID- 22473888
TI  - Bronchiolitis: too-familiar yet too-mysterious disease of childhood.

PMID- 22473889
TI  - Intervention research, randomised trials and knowledge for decision-making.

PMID- 22473890
TI  - Protocols, policy making and scientific progress.

PMID- 22473891
TI  - Walking gently: some cautions in developing a procedural view of knowledge.

PMID- 22473892
TI  - What works, for whom, in what contexts, who needs to know, and how will they use
      the information (if at all): a response.

PMID- 22473893
TI  - Induction of the chick columella and its integration with the inner ear.
AB  - BACKGROUND: The auditory complex of the chick, like that of humans, is made of
      intimate and highly ordered connections between the inner ear, the middle ear,
      and the outer ear. Unlike mammals, the middle ear of chick has only one ossicle,
      known as the columella. The independent lineages of the two suggest that some
      mechanism must exist that ensures the connectivity between the inner ear and the
      columella; however, the basis of integration is not known. RESULTS: Using quail
      chick chimeras, we demonstrate that columella development depends on signaling
      interactions. Specifically, both pharyngeal endoderm and cranial paraxial
      mesoderm can alter the morphology of the columella. Only a discrete region of
      pharyngeal endoderm exerts this patterning activity, and this region is specified
      by the overlying paraxial mesoderm. CONCLUSIONS: Paraxial mesoderm is also used
      in the induction of the inner ear, thus we propose that this overlapping source
      of signalling cues in both middle and inner ear development may underlie the
      integration of these structures.

PMID- 22473894
TI  - Deconstructing visual scenes in cortex: gradients of object and spatial layout
      information.
AB  - Real-world visual scenes are complex cluttered, and heterogeneous stimuli
      engaging scene- and object-selective cortical regions including parahippocampal
      place area (PPA), retrosplenial complex (RSC), and lateral occipital complex
      (LOC). To understand the unique contribution of each region to distributed scene
      representations, we generated predictions based on a neuroanatomical framework
      adapted from monkey and tested them using minimal scenes in which we
      independently manipulated both spatial layout (open, closed, and gradient) and
      object content (furniture, e.g., bed, dresser). Commensurate with its strong
      connectivity with posterior parietal cortex, RSC evidenced strong spatial layout
      information but no object information, and its response was not even modulated by
      object presence. In contrast, LOC, which lies within the ventral visual pathway,
      contained strong object information but no background information. Finally, PPA,
      which is connected with both the dorsal and the ventral visual pathway, showed
      information about both objects and spatial backgrounds and was sensitive to the
      presence or absence of either. These results suggest that 1) LOC, PPA, and RSC
      have distinct representations, emphasizing different aspects of scenes, 2) the
      specific representations in each region are predictable from their patterns of
      connectivity, and 3) PPA combines both spatial layout and object information as
      predicted by connectivity.

PMID- 22473896
TI  - Early decline in progenitor diversity in the marmoset lateral ventricle.
AB  - The lateral ventricle (LV) of the adult rodent brain harbors neural stem cells
      (NSCs) that continue to generate new neurons throughout life. NSCs located in
      defined areas of the LV walls generate progenitors with distinct transcriptional
      profiles that are committed to specific neuronal fates. Here, we assessed if such
      diversity of NSCs also exist in the adult common marmoset, a widely used primate
      species in basic and clinical neuroscience research. We first investigated the 3D
      distributions of proliferative progenitors and committed neuroblasts in the
      marmoset forebrain. In addition to these maps, we assessed the spatial presence
      of divergent progenitor populations based on their expression of defined
      transcription factors, that is, Dlx2, Pax6, Tbr2, and Ngn2 which are
      differentially expressed by gamma-aminobutyric acidergic versus glutamatergic
      progenitors in the adult rodent forebrain. In striking contrast to rodents,
      glutamatergic progenitors were only sparse in neonates and absent from the adult
      LV, whilst present in the hippocampus. Our analyses highlight major differences
      in the diversity of NSCs of the marmoset LV compared with rodents and emphasize
      the need to address NSCs diversity in evolutionary higher order mammals
      concomitantly to rodents.

PMID- 22473895
TI  - Persistence of feelings and sentience after bilateral damage of the insula.
AB  - It has been convincingly established, over the past decade, that the human
      insular cortices are involved in processing both body feelings (such as pain) and
      feelings of emotion. Recently, however, an interpretation of this finding has
      emerged suggesting that the insular cortices are the necessary and sufficient
      platform for human feelings, in effect, the sole neural source of feeling
      experiences. In this study, we investigate this proposal in a patient whose
      insular cortices were destroyed bilaterally as a result of Herpes simplex
      encephalitis. The fact that all aspects of feeling were intact indicates that the
      proposal is problematic. The signals used to assemble the neural substrates of
      feelings hail from different sectors of the body and are conveyed by neural and
      humoral pathways to complex and topographically organized nuclei of the brain
      stem, prior to being conveyed again to cerebral cortices in the somatosensory,
      insular, and cingulate regions. We suggest that the neural substrate of feeling
      states is to be found first subcortically and then secondarily repeated at
      cortical level. The subcortical level would ensure basic feeling states while the
      cortical level would largely relate feeling states to cognitive processes such as
      decision-making and imagination.

PMID- 22473897
TI  - Concordance of qualitative bone scintigraphy results with presence of clinical
      complex regional pain syndrome 1: meta-analysis of test accuracy studies.
AB  - BACKGROUND: To date, no attempt has been made to investigate the agreement
      between qualitative bone scintigraphy (BS) and the presence of complex regional
      pain syndrome 1 (CRPS 1) and the agreement between a negative BS in the absence
      of CRPS 1. AIMS: To summarize the existing evidence quantifying the concordance
      of qualitative BS in the presence or absence of clinical CRPS 1. DATA SOURCES: We
      searched Medline, Embase, Dare and the Cochrane Library and screened
      bibliographies of all included studies. STUDY ELIGIBILITY CRITERIA: We selected
      diagnostic studies investigating the association between qualitative BS results
      and the clinical diagnosis of CRPS 1. The minimum requirement for inclusion was
      enough information to fill the two-by-two tables. RESULTS: Twelve studies met our
      inclusion criteria and were included in the meta-analysis. The pooled mean
      sensitivity of 12 two-by-two tables was 0.87 (95% CI, 0.68-0.97) and specificity
      was 0.69 (95% CI, 0.47-0.85). The pooled mean sensitivity for the subgroup with
      clearly defined diagnostic criteria (seven two-by-two tables) was 0.80 (95% CI,
      0.44-0.95) and specificity was 0.73 (95% CI, 0.40-0.91). CONCLUSIONS: Based on
      this study, clinicians must be advised that a positive BS is not necessarily
      concordant with presence of absence or CRPS 1. Given the moderate level of
      concordance between a positive BS in the absence of clinical CRPS 1, discordant
      results potentially impede the diagnosis of CRPS 1.

PMID- 22473898
TI  - Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid
      leukemia.
AB  - Dramatically improved survival associated with tyrosine kinase inhibitor (TKI)
      therapy has transformed the disease model for chronic myeloid leukemia (CML) to
      one of long-term management, but treatment success is challenged with poor
      medication adherence. Many risk factors associated with poor adherence can be
      ameliorated by close monitoring, dose modification, and supportive care.
      Controlling risk factors for poor adherence in combination with patient education
      that includes direct communication between the health care team and the patient
      are essential components for maximizing the benefits of TKI therapy.

PMID- 22473900
TI  - Convergent synthesis of near-infrared absorbing, "push-pull", bisthiophene
      substituted, zinc(II) phthalocyanines and their application in dye-sensitized
      solar cells.
AB  - Zinc(II) phthalocyanine dyes that contain triarylamine-terminated bisthiophene
      and hexylbisthiophene groups have been synthesized by a convergent approach by
      using carboxytriiodo-ZnPc as a precursor. Further transformation of the iodo
      groups by a Pd-catalyzed reaction allowed easy preparation of further extended pi
      conjugated carboxy-ZnPcs. These dyes have been used as sensitizers in dye
      sensitized solar cells, which exhibit a panchromatic response and moderate
      overall efficiencies.

PMID- 22473899
TI  - MUC1-C oncoprotein confers androgen-independent growth of human prostate cancer
      cells.
AB  - BACKGROUND: The mucin 1 (MUC1) heterodimeric oncoprotein is overexpressed in
      human prostate cancers with aggressive pathologic and clinical features. However,
      few insights are available regarding the functional role of MUC1 in prostate
      cancer. METHODS: Effects of MUC1-C on androgen receptor (AR) expression were
      determined by RT-PCR, immunoblotting and AR promoter activation.
      Coimmunoprecipitations, direct binding assays, and chromatin immunoprecipitation
      (ChIP) studies were performed to assess the interaction between MUC1-C and AR.
      Cells were analyzed for invasion, growth in androgen-depleted medium, and
      sensitivity to MUC1-C inhibitors. RESULTS: The present studies in androgen
      dependent LNCaP and LAPC4 prostate cancer cells demonstrate that the oncogenic
      MUC1-C subunit suppresses AR expression. The results show that MUC1-C activates a
      posttranscriptional mechanism involving miR-135b-mediated downregulation of AR
      mRNA levels. The results further demonstrate that MUC1-C forms a complex with AR
      through a direct interaction between the MUC1-C cytoplasmic domain and the AR DNA
      binding domain (DBD). In addition, MUC1-C associates with AR in a complex that
      occupies the PSA promoter. The interaction between MUC1-C and AR is associated
      with induction of the epithelial-mesenchymal transition (EMT) and increased
      invasion. MUC1-C also conferred growth in androgen-depleted medium and resistance
      to bicalutamide treatment. Moreover, expression of MUC1-C resulted in sensitivity
      to the MUC1-C inhibitor GO-203 with inhibition of growth in vitro. GO-203
      treatment also inhibited growth of established tumor xenografts in nude mice.
      CONCLUSIONS: These findings indicate that MUC1-C suppresses AR expression in
      prostate cancer cells and confers a more aggressive androgen-independent
      phenotype that is sensitive to MUC1-C inhibition.

PMID- 22473901
TI  - Hepatitis B virus X protein stabilizes amplified in breast cancer 1 protein and
      cooperates with it to promote human hepatocellular carcinoma cell invasiveness.
AB  - Chronic infection of hepatitis B virus (HBV) is closely associated with the
      development of human hepatocellular carcinoma (HCC). HBV X protein (HBx) plays a
      key role in the progression of HCC. We recently found that amplified in breast
      cancer 1 (AIB1) protein is overexpressed in 68% of human HCC specimens and
      promotes HCC progression by enhancing cell proliferation and invasiveness. Given
      that both HBx and AIB1 play important oncogenic roles in HCC, we aimed to
      determine whether they could cooperatively promote human HCC development. Herein,
      we show that HBx-positive HCC tissues had a higher level of AIB1 protein,
      compared to HBx-negative HCC tissues. A positive correlation between HBx protein
      level and AIB1 protein level was established in HCC specimens. Without affecting
      its messenger RNA level, HBx induced a significant increase of the protein level
      of AIB1, which correlated with a significant extension of the half-life of AIB1
      protein. Mechanistically, HBx could interact with AIB1 to prevent the interaction
      between envelope protein 3 ubiquitin ligase F-box and WD repeat domain containing
      7 (Fbw7)alpha and AIB1, then inhibited the Fbw7alpha-mediated ubiquitination and
      degradation of AIB1. In addition, reporter assays and chromatin
      immunoprecipitation assays revealed that both HBx and AIB1 were recruited to
      matrix metalloproteinase-9 (MMP-9) promoter to enhance MMP-9 promoter activity
      cooperatively. Consistently, HBx and AIB1 cooperatively enhanced MMP-9 expression
      in HepG2 cells, which, in turn, increased cell-invasive ability. CONCLUSION: Our
      study demonstrates that HBx can stabilize AIB1 protein and cooperate with it to
      promote human HCC cell invasiveness, highlighting the essential role of the cross
      talk between HBx and AIB1 in HBV-related HCC progression.

PMID- 22473902
TI  - Peptide bond tautomerization induced by divalent metal ions: characterization of
      the iminol configuration.

PMID- 22473904
TI  - Modified mini-Lothrop/extended Draf IIB procedure for contralateral frontal sinus
      disease: a case series.
AB  - BACKGROUND: Management of frontal sinus disease represents one of the most
      challenging aspects of endoscopic sinus surgery. In select cases, anatomic
      variations (outflow tract osteoneogenesis, scarring, fat prolapsed from previous
      orbital decompression) may hinder ipsilateral access using traditional endoscopic
      approaches. We previously proposed a modification of the standard Draf IIB
      procedure which incorporates a frontal intersinus septectomy (modified mini
      Lothrop procedure/extended Draf IIB) to access and manage recalcitrant unilateral
      frontal sinus obstruction inaccessible ipsilaterally in cadaver specimens. In
      this study, we describe this technique, and present a case series of 4 patients
      who benefited from this approach. METHODS: A retrospective analysis at a large
      tertiary referral center was performed on all patients undergoing frontal sinus
      surgery between July 2008 and June 2011. Four patients with frontal sinus recess
      obstruction inaccessible from the ipsilateral side and treated with the modified
      mini-Lothrop procedure/extended Draf IIB were identified. RESULTS: All 4 patients
      underwent successful frontal sinusotomies via a Modified mini-Lothrop
      procedure/extended Draf IIB without complications and had a patent drainage
      pathway assessed endoscopically after a mean follow-up of 21 (range, 9-28)
      months. CONCLUSION: The modified mini-Lothrop procedure/extended Draf IIB
      represents a feasible approach and adequate alternative to more traditional
      endoscopic and open frontal sinus procedures in select cases. This modification
      was successful in addressing difficult to access unilateral frontal sinus disease
      in this small cohort.

PMID- 22473905
TI  - Under the tip of the iceberg: psychological factors in incontinence.
AB  - AIMS: To highlight two main psychological factors (cognitive barriers and safety
      behaviors) involved in the development and maintenance of emotional distress in
      patients with urinary incontinence (UI) and thus facilitate a better
      understanding of this condition and contribute to a more comprehensive treatment.
      MATERIALS AND METHODS: Articles and books were reviewed up to December 2010 using
      a non-systematic research in MEDLINE and PsycINFO, focusing on the situations
      more frequently seen in our clinical experience. RESULTS: Several emotional
      symptoms that hinder a person's ability to benefit from urological treatment were
      found. An "accident" places a person at risk of developing a constant state of
      heightened worry and increased vigilance that predisposes the individual to
      develop significant anxiety and depression. Cognitive barriers such as
      dysfunctional beliefs, automatic negative thoughts, and cognitive biases are
      frequent. They affect patients' behavior and influence the development of coping
      strategies (safety-seeking behaviors) to manage symptoms and prevent feared
      consequences. Cognitions may act as barriers that lead to a misperception of
      one's health and maintain emotional distress. Safety behaviors are negatively
      reinforced and prevent disconfirmation of dysfunctional cognitions, thus
      maintaining the trouble and distress. Clinical examples are outlined.
      CONCLUSIONS: Cognitive barriers and safety behaviors explain some of the atypical
      psychological patterns seen in patients with UI. Future research should be
      oriented to design multimodal interventions and assess their impact on health
      outcomes. Whenever possible, the assessment of emotional, cognitive, and
      behavioral responses in individuals with UI could improve the management of this
      condition. Cognitive-behavioral therapy should be recommended to certain
      patients.

PMID- 22473906
TI  - Hemostatic gelatin sponge is a superior matrix to matrigel for establishment of
      LNCaP human prostate cancer in nude mice.
AB  - BACKGROUND: Matrigels, solubilized basement membrane preparations, are often used
      to support tumor development in animal models. However, tumors formed by a
      mixture of tumor cells and Matrigel may vary significantly. The purpose of this
      study was to compare tumor development and growth of LNCaP human prostate cancer
      cells mixed with Matrigel or in gelatin sponges. METHODS: LNCaP cells were mixed
      with Matrigel or absorbed into VETSPON, a gelatin sponge, and inoculated into the
      subcutis of nude mice. Tumor incidence and growth rate were determined. Gene
      expression and cell growth and survival in tumor lesions were evaluated by
      immunohistochemistry (IHC), immunoblotting, and RT-PCR. RESULTS: All mice (12/12)
      inoculated with LNCaP cells in VETSPON produced tumors, compared to 70% (19/27)
      of mice injected with the cells with Matrigel. Tumor volume also varied less with
      VETSPON implants. No significant differences were observed in gene expression,
      cell growth, apoptosis, and microvessel density in tumors established from the
      two types of implants. However, in samples collected on days 1 and 4, more cells
      in Matrigel implants than those in VETSPON implants were stained positive for
      cleaved-caspase 3 and -PARP1. Expression of VEGF-A, HIF-1alpha, and Bcl-2 was
      elevated in the early VETSPON implants. CONCLUSION: These data indicate that
      VETSPON promotes tumor cell survival at the early stage of implantation and
      suggest that the gelatin sponge is superior to Matrigel in supporting development
      and progression of human prostate cancer in nude mice. This model should be
      useful for preclinical studies in nude mice using LNCaP cells.

PMID- 22473908
TI  - True submental artery perforator flap for total soft-tissue chin reconstruction.

PMID- 22473909
TI  - Genetic and sex influence on neuropathic pain-like behaviour after spinal cord
      injury in the rat.
AB  - BACKGROUND: Chronic pain of neuropathic nature after spinal cord injury (SCI) is
      common and its underlying mechanisms are poorly understood. Genes, as well as
      sex, have been implicated, but not thoroughly investigated in experimental
      genetic models for complex traits. We have previously found that inbred Dark
      Agouti (DA) rats develop more severe SCI pain-like behaviour than a major
      histocompatibility complex-congenic Piebald Virol Glaxo (PVG)-RT1(av1)  strain in
      a model of photochemically induced SCI. METHODS: In this study, a genome-wide
      linkage study in an F2 cross between the susceptible DA and resistant PVG
      RT1(av1)  strains was performed in order to explore the influence of genes and
      sex for SCI pain. RESULTS: A consistent finding was that female rats in parental,
      F1 and F2 generations displayed increased pain sensitivity at testing before
      injury and also developed mechanical hypersensitivity more rapidly and to a
      greater extent than male rats. In addition, we could identify three quantitative
      trait loci (QTLs) associated with pain-like behaviour: a sex-specific QTL on
      chromosome 2, one on chromosome 15 and on chromosome 6. Animals carrying DA
      alleles at each of these loci were more susceptible to development of mechanical
      hypersensitivity compared with rats with PVG alleles. CONCLUSION: This is the
      first whole genome QTL mapping of neuropathic pain-like behaviour in a model of
      SCI. The results provide strong support for a significant genetic and sex
      component in development of pain after SCI and provide the basis for further
      genetic dissection and positional cloning of the underlying genes.

PMID- 22473907
TI  - P-selectin genotype is associated with the development of cancer cachexia.
AB  - The variable predisposition to cachexia may, in part, be due to the interaction
      of host genotype. We analyzed 129 single nucleotide polymorphisms (SNPs) in 80
      genes for association with cachexia based on degree of weight loss (>5, >10,
      >15%) as well as weight loss in the presence of systemic inflammation (C-reactive
      protein, > 10 mg/l). 775 cancer patients were studied with a validation
      association study performed on an independently recruited cohort (n = 101) of
      cancer patients. The C allele (minor allele frequency 10.7%) of the rs6136 (SELP)
      SNP was found to be associated with weight loss >10% both in the discovery study
      (odds ratio (OR) 0.52; 95% confidence intervals (CI), 0.29-0.93; p = 0.026) and
      the validation study (OR 0.09, 95% CI 0.01-0.98, p = 0.035). In separate studies,
      induction of muscle atrophy gene expression was investigated using qPCR following
      either tumour-induced cachexia in rats or intra-peritoneal injection of
      lipopolysaccharide in mice. P-selectin was found to be significantly upregulated
      in muscle in both models. Identification of P-selectin as relevant in both animal
      models and in cachectic cancer patients supports this as a risk factor/potential
      mediator in cachexia.

PMID- 22473910
TI  - Introductory remarks for the THSNA meeting proceedings: hemostasis and thrombosis
      at the cutting edge.

PMID- 22473911
TI  - Hepatic vein arrival time as assessed by contrast-enhanced ultrasonography is
      useful for the assessment of portal hypertension in compensated cirrhosis.
AB  - The measurement of the hepatic venous pressure gradient (HVPG) for the estimation
      of portal hypertension (PH) in cirrhosis has some limitations, including its
      invasiveness. Hepatic vein arrival time (HVAT), as assessed by microbubble
      contrast-enhanced ultrasonography (CEUS), is negatively correlated with the
      histological grade of liver fibrosis because of the associated hemodynamic
      abnormalities. Anatomical and pathophysiological changes in liver
      microcirculation are the initial events leading to PH. However, the direct
      relationship between HVAT and PH has not been evaluated. The present study
      measured both HVPG and HVAT in 71 consecutive patients with compensated cirrhosis
      and analyzed the relationship between the two parameters (i.e., the derivation
      set). Results were validated in 35 compensated patients with cirrhosis at another
      medical center (i.e., the validation set). The derivation set had HVPG and HVAT
      values of 11.4 +/- 5.0 mmHg (mean +/- standard deviation; range, 2-23) and 14.1
      +/- 3.4 seconds (range, 8.4-24.2), respectively; there was a statistically
      significant negative correlation between HVPG and HVAT (r(2) = 0.545; P < 0.001).
      The area under the receiver operating characteristic curve (AUROC) was 0.973 for
      clinically significant PH (CSPH; HVPG, >= 10 mmHg), and the sensitivity,
      specificity, positive predictive value, negative predictive value, and positive
      and negative likelihood ratios for CSPH for an HVAT cut-off value of 14 seconds
      were 92.7%, 86.7%, 90.5%, 89.7%, 6.95, and 0.08, respectively. In addition, a
      shorter HVAT was associated with worse Child-Pugh score (P < 0.001) and
      esophageal varices (P = 0.018). In the validation set, there was also a
      significant negative correlation between HVAT and HVPG (r(2) = 0.538; P < 0.001),
      and AUROC = 0.953 for CSPH. HVAT was significantly correlated with PH. These
      results indicate that measuring HVAT is useful for the noninvasive prediction of
      CSPH in patients with compensated cirrhosis.

PMID- 22473912
TI  - Nickel-mediated inter- and intramolecular reductive cross-coupling of unactivated
      alkyl bromides and aryl iodides at room temperature.
AB  - A nickel-mediated intermolecular reductive cross-coupling reaction of unactivated
      alkyl bromides and aryl iodides at room temperature has been developed and
      successfully extended to less explored intramolecular versions and tandem
      cyclization-intermolecular cross-coupling. Highly stereoselective (or
      stereospecific) synthesis of linear-fused perhydrofuro[2,3-b]furan (pyran) and
      spiroketal skeletons allows rapid access to these useful building blocks, which
      would be potentially valuable in the synthesis of relevant natural products. A
      rational explanation for the formation of contiguous stereogenic centers is
      given.

PMID- 22473913
TI  - Treatment of congenital pseudarthrosis of the tibia with vascularized fibular
      periosteal transplant.
AB  - The vascularized fibular periosteal flap has been recently described and showed
      solid angio and osteogenic features. We report the use of a free vascularized
      fibular periosteal transplant in the treatment of a El-Rosasy-Paley Type III
      congenital pseudarthrosis of the tibia in a 7-year-old boy, with a prior
      unsuccessful surgery at the age of three. The contralateral fibular periosteum
      was used to replace two-thirds of the hamartomatous tibial periosteum. We did not
      proceed to debriding the focus of the pseudarthrosis nor addressed the tibial
      recurvatum or revised the previous tibial rod. Consolidation was achieved
      radiologically at 3 months, allowing for the tibial rod to be removed. One year
      postoperatively, the patient ambulated without the use of a protective orthesis
      and resumed his sports practice. This novel pathogenesis-based technique showed
      promising results and a prompt healing of such a difficult orthopedic condition.

PMID- 22473915
TI  - A microinjection protocol for the generation of transgenic killifish (Species:
      Nothobranchius furzeri).
AB  - BACKGROUND: A challenge in age research is the absence of short-lived vertebrate
      model organisms. The turquoise killifish Nothobranchius furzeri has an
      exceptionally short lifespan of 4-10 months depending on the strain. Thus, it
      possesses the shortest known maximum lifespan of a vertebrate species that can be
      bred in captivity. RESULTS: Here we show the successful introduction of DNA and
      RNA molecules into the one-cell embryo of N. furzeri. For this purpose, we
      adapted existing microinjection protocols to inject through the remarkably thick
      and robust chorion of N. furzeri's eggs. The injected DNA transgene was
      integrated into the genome and transmitted to subsequent generations as indicated
      by the expression of the fluorophore enhanced green fluorescent protein (EGFP).
      Furthermore, we could confirm a special phase during embryonic development in
      which embryogenesis occurs within a re-aggregated mass of previously dispersed
      cells as it has been described for other related cyprinodont fish species.
      CONCLUSIONS: The transgenesis protocol described here provides a basis for a
      variety of genetic manipulations including overexpression of genes and
      determining their effects on lifespan and longevity. The feasibility to perform
      transgenesis is an important step to establish N. furzeri as a new model in age
      research.

PMID- 22473914
TI  - Identification of selective inhibitors of the potassium channel Kv1.1-1.2((3)) by
      high-throughput virtual screening and automated patch clamp.
AB  - Two voltage-dependent potassium channels, Kv1.1 (KCNA1) and Kv1.2 (KCNA2), are
      found to co-localize at the juxtaparanodal region of axons throughout the nervous
      system and are known to co-assemble in heteromultimeric channels, most likely in
      the form of the concatemer Kv1.1-1.2((3)) . Loss of the myelin sheath, as is
      observed in multiple sclerosis, uncovers the juxtaparanodal region of nodes of
      Ranvier in myelinated axons leading to potassium conductance, resulting in loss
      of nerve conduction. The selective blocking of these Kv channels is therefore a
      promising approach to restore nerve conduction and function. In the present
      study, we searched for novel inhibitors of Kv1.1-1.2((3)) by combining a virtual
      screening protocol and electrophysiological measurements on a concatemer Kv1.1
      1.2((3)) stably expressed in Chinese hamster ovary K1 (CHO-K1) cells. The
      combined use of four popular virtual screening approaches (eHiTS, FlexX, Glide,
      and Autodock-Vina) led to the identification of several compounds as potential
      inhibitors of the Kv1.1-1.2((3)) channel. From 89 electrophysiologically
      evaluated compounds, 14 novel compounds were found to inhibit the current carried
      by Kv1.1-1.2((3)) channels by more than 80 % at 10 MUM. Accordingly, the IC(50)
      values calculated from concentration-response curve titrations ranged from 0.6 to
      6 MUM. Two of these compounds exhibited at least 30-fold higher potency in
      inhibition of Kv1.1-1.2((3)) than they showed in inhibition of a set of cardiac
      ion channels (hERG, Nav1.5, and Cav1.2), resulting in a profile of selectivity
      and cardiac safety. The results presented herein provide a promising basis for
      the development of novel selective ion channel inhibitors, with a dramatically
      lower demand in terms of experimental time, effort, and cost than a sole high
      throughput screening approach of large compound libraries.

PMID- 22473916
TI  - Facile bucky-bowl synthesis by regiospecific cove-region closure by HF
      elimination.

PMID- 22473917
TI  - 2012 update of the 2008 American College of Rheumatology recommendations for the
      use of disease-modifying antirheumatic drugs and biologic agents in the treatment
      of rheumatoid arthritis.

PMID- 22473918
TI  - Rheumatoid arthritis disease activity measures: American College of Rheumatology
      recommendations for use in clinical practice.
AB  - OBJECTIVE: Although the systematic measurement of disease activity facilitates
      clinical decision making in rheumatoid arthritis (RA), no recommendations
      currently exist on which measures should be applied in clinical practice in the
      US. The American College of Rheumatology (ACR) convened a Working Group (WG) to
      comprehensively evaluate the validity, feasibility, and acceptability of
      available RA disease activity measures and derive recommendations for their use
      in clinical practice. METHODS: The Rheumatoid Arthritis Clinical Disease Activity
      Measures Working Group conducted a systematic review of the literature to
      identify RA disease activity measures. Using exclusion criteria, input from an
      Expert Advisory Panel (EAP), and psychometric analysis, a list of potential
      measures was created. A survey was administered to rheumatologists soliciting
      input. The WG used these survey results in conjunction with the psychometric
      analyses to derive final recommendations. RESULTS: Systematic review of the
      literature resulted in identification of 63 RA disease activity measures.
      Application of exclusion criteria and ratings by the EAP narrowed the list to 14
      measures for further evaluation. Practicing rheumatologists rated 9 of these 14
      measures as most useful and feasible. From these 9 measures, the WG selected 6
      with the best psychometric properties for inclusion in the final set of ACR
      recommended RA disease activity measures. CONCLUSION: We recommend the Clinical
      Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte
      sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II,
      Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease
      Activity Index because they are accurate reflections of disease activity; are
      sensitive to change; discriminate well between low, moderate, and high disease
      activity states; have remission criteria; and are feasible to perform in clinical
      settings.

PMID- 22473919
TI  - Updated recommendations for the treatment of rheumatoid arthritis: another step
      on a long road.

PMID- 22473921
TI  - Brain activity underlying impaired continence control in older women with
      overactive bladder.
AB  - AIMS: To identify, in subjects with overactive bladder (OAB), differences in
      brain activity between those who maintained and those who lost bladder control
      during functional magnetic resonance imaging (fMRI) of the brain with
      simultaneous urodynamics. METHODS: Secondary analysis of a cohort of older women
      (aged >60) with proven urgency urinary incontinence, who, in the scanner, either
      developed detrusor overactivity and incontinence (the "DO group") or did not (the
      "no DO" group). A priori hypothesis: during urgency provoked by bladder filling,
      without DO, activity in regions related to continence control is diminished in
      the DO group; specifically (1a) less activation in supplementary motor area (SMA)
      and (1b) less deactivation in prefrontal cortex (PFC) and parahippocampal complex
      (PH). We also explored phenotypic (clinical and urodynamic) differences between
      the groups. RESULTS: During urgency preceding DO, the DO group showed stronger
      activation in SMA and adjacent regions (hypothesis 1a rejected), and less
      deactivation in PH but no significant difference in PFC (hypothesis 1b partially
      accepted). These subjects were older, with more changes in brain's white matter,
      decreased tolerance of bladder filling and greater burden of incontinence.
      CONCLUSIONS: (1) In older women with OAB, brain activity in the SMA is greater
      among those with more easily elicitable DO, suggesting a compensatory response to
      failure of control elsewhere. (2) OAB is heterogeneous; one possible phenotype
      shows severe functional impairment attributable partly to age-related white
      matter changes. (3) Functional brain imaging coupled with urodynamics may provide
      CNS markers of impaired continence control in subjects with OAB.

PMID- 22473922
TI  - The impact of dissociation on PTSD treatment with cognitive processing therapy.
AB  - BACKGROUND: This secondary analysis of data from a randomized controlled trial of
      cognitive processing therapy (CPT) and its constituent components investigated
      whether dissociation decreased over the course of treatment primarily targeting
      symptoms of posttraumatic stress disorder (PTSD) and explored whether levels of
      dissociation predicted treatment outcome differentially by treatment condition.
      METHODS: An intention to treat sample of 150 women were randomized to CPT,
      cognitive therapy only (CPT-C) or written trauma accounts only (WA). Dissociation
      was measured by the dissociation subscale of the Traumatic Stress Inventory and
      the Multiscale Dissociation Inventory. RESULTS: Multilevel regression analyses
      revealed significant decreases in dissociation that did not vary as a function of
      treatment condition. Growth curve modeling revealed significant treatment
      condition by dissociation interactions such that the impact of pretreatment
      levels of dissociation impacted the treatment conditions differently.
      CONCLUSIONS: Women who endorsed low pretreatment levels of dissociation responded
      most efficiently to CPT-C, whereas women with the highest levels of dissociation,
      in particular high levels of depersonalization, responded better to CPT.

PMID- 22473923
TI  - High NRBP1 expression in prostate cancer is linked with poor clinical outcomes
      and increased cancer cell growth.
AB  - BACKGROUND: We recently established the rationale that NRBP1 (nuclear receptor
      binding protein 1) has a potential growth-promoting role in cell biology. NRBP1
      interacts directly with TSC-22, a potential tumor suppressor gene that is
      differently expressed in prostate cancer. Consequently, we analyzed the role of
      NRBP1 expression in prostate cancer cell lines and its expression on prostate
      cancer tissue microarrays (TMA). METHODS: The effect of NRBP1 expression on tumor
      cell growth was analyzed by using RNAi. NRBP1 protein expression was evaluated on
      two TMAs containing prostate samples from more than 1,000 patients. Associations
      with clinico-pathological features, the proliferation marker Ki67 and survival
      data were analyzed. RESULTS: RNAi mediated silencing of NRBP1 expression in
      prostate cancer cell lines resulted in reduced cell growth (P < 0.05). TMA
      analysis revealed NRBP1 protein expression in benign prostate hyperplasia in 6%
      as compared to 60% in both, high-grade intraepithelial neoplasia and prostate
      cancer samples. Strong NRBP1 protein expression was restricted to prostate cancer
      and correlated with higher expression of the proliferation marker Ki67 (P <
      0.05). Further, patients with strong NRBP1 protein expression showed poor
      clinical outcomes (P < 0.05). Analysis of matched localized cancer tissues before
      and after castration revealed that post-therapy-related repression of NRBP1
      expression was significantly associated with better overall survival.
      CONCLUSIONS: We demonstrate that expression of NRBP1 is up-regulated during the
      progression of prostate cancer and that high NRBP1 expression is linked with poor
      prognosis and enhanced tumor cell growth.

PMID- 22473924
TI  - A computational study of odorant transport and deposition in the canine nasal
      cavity: implications for olfaction.
AB  - Olfaction begins when an animal draws odorant-laden air into its nasal cavity by
      sniffing, thus transporting odorant molecules from the external environment to
      olfactory receptor neurons (ORNs) in the sensory region of the nose. In the dog
      and other macrosmatic mammals, ORNs are relegated to a recess in the rear of the
      nasal cavity that is comprised of a labyrinth of scroll-like airways. Evidence
      from recent studies suggests that nasal airflow patterns enhance olfactory
      sensitivity by efficiently delivering odorant molecules to the olfactory recess.
      Here, we simulate odorant transport and deposition during steady inspiration in
      an anatomically correct reconstructed model of the canine nasal cavity. Our
      simulations show that highly soluble odorants are deposited in the front of the
      olfactory recess along the dorsal meatus and nasal septum, whereas moderately
      soluble and insoluble odorants are more uniformly deposited throughout the entire
      olfactory recess. These results demonstrate that odorant deposition patterns
      correspond with the anatomical organization of ORNs in the olfactory recess.
      Specifically, ORNs that are sensitive to a particular class of odorants are
      located in regions where that class of odorants is deposited. The correlation of
      odorant deposition patterns with the anatomical organization of ORNs may
      partially explain macrosmia in the dog and other keen-scented species.

PMID- 22473925
TI  - Synergistic effect of palladium and copper catalysts: catalytic cyclizative
      dimerization of ortho-(1-alkynyl)benzamides leading to axially chiral 1,3
      butadienes.
AB  - Two is better than one: In the presence of Pd(OAc)(2) and Cu(OAc)(2), o-(1
      alkynyl)benzamides 1 were converted into bis-iminobenzoisofurans with an axially
      chiral 1,3-diene 2 unit. The coexistence of both Pd and Cu catalysts was found to
      be essential for both the cyclizative dimerization process and for the observed
      unusual cyclization mode.

PMID- 22473926
TI  - Salmonella-related mycotic aortic aneurysm heralding a diagnosis of multiple
      myeloma.

PMID- 22473928
TI  - Standards for helmets.

PMID- 22473929
TI  - Emergency department visits and infections.

PMID- 22473931
TI  - Addiction is not a disease.

PMID- 22473932
TI  - In defence of older drivers.

PMID- 22473933
TI  - A diketopyrrolopyrrole-based colorimetric and fluorescent probe for cyanide
      detection.
AB  - Red means CN: A new type of diketopyrrolopyrrole-based chromophore has been
      synthesized as a colorimetric and fluorescent probe for the detection of cyanide
      using only two reaction steps. Through the addition of cyanide to the
      chromophore, the fluorescence emission and color were greatly changed in a highly
      sensitive and selective manner.

PMID- 22473934
TI  - Myxoid liposarcoma: a case report of a sentinel metastasis to the parotid gland
      with molecular confirmation.
AB  - Myxoid liposarcoma is a subtype of liposarcoma with a predilection for the deep
      soft tissues of the extremities that accounts approximately for 10% of all adult
      soft tissue sarcomas. We report a case of a metastatic myxoid liposarcoma to the
      parotid gland, with fine-needle aspiration cytology correlation and molecular
      characterization. The lesion was diagnosed in a 53-year-old Hispanic male who
      presented with a left posterior thigh mass. A core needle biopsy established the
      diagnosis of myxoid liposarcoma. The patient underwent limb-sparing, wide local
      excision of the malignancy and later presented with an initial metastatic lesion
      to the parotid gland. The diagnosis of metastatic myxoid liposarcoma was rendered
      by fine-needle aspiration cytology with cell block preparation, and molecular
      confirmation. Although myxoid/round cell liposarcomas are classically described
      as having minimal pleomorphism on cytologic material, we encountered significant
      pleomorphism in our case. Therefore, a diagnosis of myxoid/round cell liposarcoma
      should still be a diagnostic consideration even if markedly pleomorphic cells are
      seen in fine-needle aspiration biopsies.

PMID- 22473935
TI  - Clinical and genetic findings in a large cohort of patients with ryanodine
      receptor 1 gene-associated myopathies.
AB  - Ryanodine receptor 1 (RYR1) mutations are a common cause of congenital myopathies
      associated with both dominant and recessive inheritance. Histopathological
      findings frequently feature central cores or multi-minicores, more rarely, type 1
      predominance/uniformity, fiber-type disproportion, increased internal nucleation,
      and fatty and connective tissue. We describe 71 families, 35 associated with
      dominant RYR1 mutations and 36 with recessive inheritance. Five of the dominant
      mutations and 35 of the 55 recessive mutations have not been previously reported.
      Dominant mutations, typically missense, were frequently located in recognized
      mutational hotspot regions, while recessive mutations were distributed throughout
      the entire coding sequence. Recessive mutations included nonsense and splice
      mutations expected to result in reduced RyR1 protein. There was wide clinical
      variability. As a group, dominant mutations were associated with milder
      phenotypes; patients with recessive inheritance had earlier onset, more weakness,
      and functional limitations. Extraocular and bulbar muscle involvement was almost
      exclusively observed in the recessive group. In conclusion, our study reports a
      large number of novel RYR1 mutations and indicates that recessive variants are at
      least as frequent as the dominant ones. Assigning pathogenicity to novel
      mutations is often difficult, and interpretation of genetic results in the
      context of clinical, histological, and muscle magnetic resonance imaging findings
      is essential.

PMID- 22473936
TI  - Paid care work and depression: a longitudinal study of antidepressant treatment
      in female eldercare workers before and after entering their profession.
AB  - BACKGROUND: Previous studies have reported that employees in paid care work
      (e.g., child, health, and elderly care) have increased rates of hospitalization
      with depression and treatment with antidepressants. It is unclear, however,
      whether these findings reflect a causal effect of the work on employee mental
      health or a selection into these professions. METHODS: We examined prevalences of
      antidepressant purchases during 1995-2008 in a cohort of female eldercare workers
      who entered their profession in 2004 (n = 1,946). These yearly prevalences were
      compared to those of a representative sample of the female Danish working
      population (n = 4,201). Trends in antidepressants prevalences were examined using
      generalized estimation equations. Further, to account for bias by treatment
      seeking, we compared self-reported depressive symptoms in 2005 measured by the
      mental health scale from the SF-36. RESULTS: Female eldercare workers had
      consistently higher prevalence of antidepressant treatment than the general
      female working population. The eldercare workers were also more likely to suffer
      from depressive symptoms in 2005 (standardized prevalence ratio = 1.28, 95% CI =
      1.09-1.49). Prevalences of antidepressant treatment increased during follow up
      for both cohorts, with similar estimated odds ratios of about 1.15 per year. The
      trend in the antidepressant prevalences for the eldercare workers was unchanged
      by entering eldercare work. CONCLUSIONS: These findings indicate that female
      eldercare workers are at increased risk of depression. Further, as the trend in
      the antidepressant prevalences among the eldercare workers was similar before and
      after entering their profession, the results suggest that this increased risk is
      due to selection into the profession.

PMID- 22473937
TI  - Experimental evaluation of CH-pi interactions in a protein core.
AB  - CH-pi stacks up! Using the protein alpha(2) D as a model system, we estimate that
      a CH-pi contact between cyclohexylalanine (Cha) and phenylalanine (F) contributes
      approximately -0.7 kcal  mol(-1) to the protein stability. The stacking F-Cha
      pairs are sequestered in the core of the protein, where water interference does
      not exist (see figure). Therefore, the observed energetic gain should represent
      the inherent magnitude and upper limit of the CH-pi interactions.

PMID- 22473938
TI  - Lamellarins as inhibitors of P-glycoprotein-mediated multidrug resistance in a
      human colon cancer cell line.
AB  - Chemical analysis of a Didemnum sp. (CMB-01656) collected during scientific Scuba
      operations off Wasp Island, New South Wales, yielded five new lamellarins A1 (1),
      A2 (2), A3 (3), A4 (4) and A5 (5) and eight known lamellarins C (6), E (7), K
      (8), M (9), S (10), T (11), X (12) and chi (13). Analysis of a second Didemnum
      sp. (CMB-02127) collected during scientific trawling operations along the
      Northern Rottnest Shelf, Western Australia, yielded the new lamellarin A6 (14)
      and two known lamellarins G (15) and Z (16). Structures were assigned to 1-16 on
      the basis of detailed spectroscopic analysis with comparison to literature data
      and authentic samples. Access to this unique library of natural lamellarins (1
      16) provided a rare opportunity for structure-activity relationship (SAR)
      investigations, probing interactions between lamellarins and the ABC transporter
      efflux pump P-glycoprotein (P-gp) with a view to reversing multidrug resistance
      in a human colon cancer cell line (SW620 Ad300). These SAR studies, which were
      expanded to include the permethylated lamellarin derivative (17) and a series of
      lamellarin-inspired synthetic coumarins (19-24) and isoquinolines (25-26),
      successfully revealed 17 as a promising new non-cytotoxic P-gp inhibitor
      pharmacophore.

PMID- 22473939
TI  - Inherited genetic variation and overall survival following follicular lymphoma.
AB  - Follicular lymphoma (FL) has variable progression and survival, and improved
      identification of patients at high risk for progression would aid in identifying
      patients most likely to benefit from alternative therapy.In a sample of 244 FL
      cases identified during a population-based case-control study of non-Hodgkin
      lymphoma (NHL), we examined 6,679 tag SNPs in 488 gene regions for associations
      with overall FL survival. Over a median follow-up of 89 months with 65 deaths in
      this preliminary study, we identified 5 gene regions (BMP7, GALNT12,DUSP2,
      GADD45B, and ADAM17) that were associated with overall survival from FL. Results
      did not meet the criteria for statistical significance after adjustment for
      multiple hypothesis testing. These results,which support a role for host factors
      in determining the variable progression of FL, serve as an initial examination
      that can inform future studies of genetic variation and FL survival. However,
      they require replication in independent populations, as well as assessment in
      rituximab-treated patients.

PMID- 22473941
TI  - Aging modulates susceptibility to mouse liver Mallory-Denk body formation.
AB  - Mallory-Denk bodies (MDBs) are hepatocyte cytoplasmic inclusions found in several
      liver diseases and consist primarily of the cytoskeletal proteins, keratins 8 and
      18 (K8/K18). Recent evidence indicates that the extent of stress-induced protein
      misfolding, a K8>K18 overexpression state, and transglutaminase-2 activation
      promote MDB formation. In addition, the genetic background and gender play an
      important role in mouse MDB formation, but the effect of aging on this process is
      unknown. Given that oxidative stress increases with aging, the authors
      hypothesized that aging predisposes to MDB formation. They used an established
      mouse MDB model-namely, feeding non-transgenic male FVB/N mice (1, 3, and 8
      months old) with 3,5 diethoxycarbonyl-1,4-dihydrocollidine for 2 months. MDB
      formation was assessed using immunofluorescence staining and biochemically by
      demonstrating keratin and ubiquitin-containing crosslinks generated by
      transglutaminase-2. Immunofluorescence staining showed that old mice had a
      significant increase in MDB formation compared with young mice. MDB formation
      paralleled the generation of high molecular weight ubiquitinated keratin
      containing complexes and induction of p62. Old mouse livers had increased
      oxidative stress. In addition, 20S proteasome activity and autophagy were
      decreased, and endoplasmic reticulum stress was increased in older livers.
      Therefore, aging predisposes to experimental MDB formation, possibly by decreased
      activity of protein degradation machinery.

PMID- 22473940
TI  - Tropomodulin 1 constrains fiber cell geometry during elongation and maturation in
      the lens cortex.
AB  - Lens fiber cells exhibit a high degree of hexagonal packing geometry, determined
      partly by tropomodulin 1 (Tmod1), which stabilizes the spectrin-actin network on
      lens fiber cell membranes. To ascertain whether Tmod1 is required during
      epithelial cell differentiation to fiber cells or during fiber cell elongation
      and maturation, the authors quantified the extent of fiber cell disorder in the
      Tmod1-null lens and determined locations of disorder by confocal microscopy and
      computational image analysis. First, nearest neighbor analysis of fiber cell
      geometry in Tmod1-null lenses showed that disorder is confined to focal patches.
      Second, differentiating epithelial cells at the equator aligned into ordered
      meridional rows in Tmod1-null lenses, with disordered patches first observed in
      elongating fiber cells. Third, as fiber cells were displaced inward in Tmod1-null
      lenses, total disordered area increased due to increased sizes (but not numbers)
      of individual disordered patches. The authors conclude that Tmod1 is required
      first to coordinate fiber cell shapes and interactions during tip migration and
      elongation and second to stabilize ordered fiber cell geometry during maturation
      in the lens cortex. An unstable spectrin-actin network without Tmod1 may result
      in imbalanced forces along membranes, leading to fiber cell rearrangements during
      elongation, followed by propagation of disorder as fiber cells mature.

PMID- 22473943
TI  - Adults with intellectual disabilities and their carers as researchers and
      participants in a RCT.
AB  - BACKGROUND: This article describes the process of including people with
      intellectual disabilities (ID) and carers of people with ID as researchers and
      participants in randomised controlled trial (RCT) research. People with ID are
      rarely involved in research about their health, either as researchers or
      participants. Carers are often included as research informants, but family carers
      are rarely involved as researchers. METHOD: Four teams of researchers each
      comprising a researcher with ID, a supporting professional and a carer
      researcher, were recruited to complete a health intervention RCT. Accessible
      measures were selected and/or devised. Baseline interviews were completed by
      researchers with ID and/or carers of people with ID by asking participants with
      ID and/or carers of the participant about the health of the person with ID.
      Follow-up health interviews were administered after the intervention had been in
      place for a year. RESULTS: The researchers completed 331 interviews with carers
      and 196 with participants with ID. Over 50% of participants with ID completed
      baseline assessments. Positive feedback on the process and outcomes was given by
      the researchers involved. CONCLUSION: The inclusion of people with ID both as
      researchers and as participants was achieved through an appropriate design,
      strong research partnerships, adequate and flexible resources, promotion of
      teamwork and a strong task focus.

PMID- 22473944
TI  - Cross-cultural validation of a measure of felt stigma in people with intellectual
      disabilities.
AB  - BACKGROUND: One trade-off for increased independence of adults with intellectual
      disabilities in developing countries is that they may find themselves more
      exposed to the negative perceptions held by the general population regarding the
      mentally ill and disabled. The aim of this study was to adapt and translate a
      tool to measure felt stigma in people with intellectual disabilities designed in
      the United Kingdom (U.K.) to make it culturally viable, and to determine its
      reliability and validity in the multi-ethnic and multilingual context of South
      Africa (S.A.) and to compare the item responses and factor structures of the tool
      between the U.K. and S.A. METHODS: We translated the tool into local languages
      and refined it by conducting focus groups and pilot studies with professionals
      and adults with intellectual disabilities, after which test-retest reliability,
      factor analysis and internal consistency were calculated. RESULTS: Participants
      were from three different population groups: Afrikaans (n = 71; 37%), English (n
      = 67; 35%) and Xhosa (n = 53; 28%), who had mild (n = 106; 56%) or moderate
      intellectual disabilities (n = 85; 44%). 98 (51%) were re-interviewed. The
      resulting international version of the perceived stigma measure consisted of 10
      questions with good test-retest reliability (kappa ranging from 0.41 to 0.59) and
      a similar factor structure to the UK version, despite including a different set
      of questions. CONCLUSIONS: There is evidence for the validity of felt stigma
      ratings reported by adults with intellectual disabilities, despite different
      cultural and health service contexts.

PMID- 22473945
TI  - Longitudinal study of parents' impact on quality of life of children and young
      adults with intellectual disabilities.
AB  - BACKGROUND: Earlier research has distinguished five domains of Quality of life
      (QoL) for people with ID: material well-being, development and activity, physical
      well-being, social well-being, and emotional well-being. We investigated parents'
      perspectives on these domains and QoL for children and young adults with ID and
      hypothesized that parents' well-being would be a predictive factor in QoL of
      their children with ID. METHODS: Our longitudinal study administered
      questionnaires to parents at T0 (n = 147) and T1 (n = 108). The inclusion
      criteria were: (i) the child's age 0-24 years and (ii) the child's intellectual
      disability (IQ < 70 or IQ < 85 in combination with behavioural problems).
      RESULTS: Social well-being of parents (P <= 0.001), changes in parents' social
      well-being (P <= 0.01) and changes in children's social well-being (P <= 0.05)
      were strong predictors of QoL for children with ID. Emotional well-being of
      children with ID (P <= 0.01), changes in children's emotional well-being (P <=
      0.01) and changes in emotional well-being of parents (P <=0.05) also predicted
      QoL of children with ID. Material well-being of parents, and health, development
      and activity of the children were not predictors. CONCLUSION: Our study revealed
      that predictors of QoL in children and young adults with ID occurred in the
      following domains: physical well-being (children), social well-being (parents and
      children) and emotional well-being (parents and children).

PMID- 22473946
TI  - Interpersonal sources of conflict in young people with and without mild to
      moderate intellectual disabilities at transition from adolescence to adulthood.
AB  - BACKGROUND: Interpersonal conflict is a source of stress and contributes to poor
      mental health in people with mild to moderate intellectual disabilities.
      Understanding the contexts in which conflict typically occurs can better equip
      services to help people with such difficulties. However, existing studies into
      the contexts of conflict have included participants with wide-ranging ages and
      may not reflect the experiences of young adults in particular. MATERIALS AND
      METHODS: Twenty-six young adults (16-20 years) with intellectual disabilities and
      20 non-disabled young adults completed a semi-structured interview about a recent
      experience of interpersonal conflict. Participants were asked to describe their
      beliefs and feelings about the event and their subsequent response. RESULTS:
      Participants with intellectual disabilities were more likely to encounter
      conflict with strangers or peers outside their friendship group and to describe
      incidents of aggression than non-disabled participants. They were also more
      likely to characterize the other person globally as 'bad' and to perceive the
      other's actions as being personally directed at them. Young women with
      intellectual disabilities were less likely to describe responding aggressively to
      incidents. CONCLUSIONS: Findings suggest that young adults with intellectual
      disabilities are often the target of overt aggression from those outside their
      inner social sphere, while their non-disabled peers are more likely to experience
      conflict with people close to them. Young adults with intellectual disabilities
      may also be more likely to feel victimized by interpersonal conflict.
      Implications of these findings and limitations of the study are discussed.

PMID- 22473947
TI  - How do people with intellectual disabilities and diabetes experience and perceive
      their illness?
AB  - INTRODUCTION: Diabetes is a significant health problem amongst people with
      intellectual disabilities, yet there is a lack of qualitative literature looking
      specifically at their experiences and perceptions of living with this chronic
      illness. METHOD: Using Interpretative Phenomenological Analysis, this study
      explored the experiences and perceptions of four people with intellectual
      disabilities and diabetes. RESULTS: Results showed that participants demonstrated
      some knowledge of the language surrounding diabetes, but considerable confusion
      and uncertainty about their illness. The impact of diabetes was described in
      terms of physical, emotional and social consequences, and participants spoke of
      diabetes in the context of co-existing health problems. CONCLUSIONS: People with
      intellectual disabilities and diabetes face many challenges when perceiving and
      coping with their illness. Gaining insight into these challenges could help
      health professionals work together more effectively and provide appropriate
      support to people with intellectual disabilities and diabetes.

PMID- 22473948
TI  - Assessing components of empathy in sex-offenders with intellectual disabilities.
AB  - BACKGROUND: Because of a lack of research investigating empathy in sex offenders
      with intellectual disabilities, this study explored empathy in sex offenders and
      non-offenders with intellectual disabilities. Specific aims were to explore
      differences between these groups on measures of the components of empathy.
      METHODS: The scores of 21 sex-offenders and 21 non-offenders with intellectual
      disabilities, matched by age, gender and IQ, were compared on the Test of
      Emotional Perception. RESULTS: No differences were found between the two groups
      across the components of empathy. However, sex offenders who had received
      treatment performed better on tasks of emotion recognition, emotion replication
      and response decision than the non-offenders. CONCLUSIONS: Further research is
      needed to understand empathy in sex offenders with intellectual disabilities
      before any recommendations can be made regarding treatment programmes.

PMID- 22473949
TI  - Targeted support and telecare in staffed housing for people with intellectual
      disabilities: impact on staffing levels and objective lifestyle indicators.
AB  - BACKGROUND: Increased provision of out-of-family residential support is required
      because of demographic changes within the intellectual disabilities population.
      Residential support now has to be provided in a climate requiring both financial
      constraint and high quality service outcomes. The aim was to evaluate the quality
      of life consequences of living with less intensive staff support, resulting from
      the introduction of more targeted staff allocation coupled with telecare.
      METHODS: The study comprised 91 participants who lived in 33 settings. The
      targeted support/telecare intervention was implemented at staggered intervals in
      25 of these settings (63 participants). Data on a range of participant and
      setting descriptors, quality of care, and a range of objective lifestyle
      indicators were collected at four points in time over 2 years. Impact of the
      intervention was evaluated using within-group comparisons over time. RESULTS:
      Comparison between pre- and post-intervention showed that staffing levels were
      significantly reduced by 23%, whereas they were constant in the absence of
      intervention. One health indicator improved in the absence of intervention and
      another improved following intervention. There were no significant changes in any
      other lifestyle indicators (safety, money, social and community activity,
      independence or choice). CONCLUSIONS: A combination of targeted support and
      telecare had no adverse short-term affect on participants' quality of life, but
      reduced staff input so it seems that they have a role to play in the strategic
      development of out-of-family placements for adults with intellectual
      disabilities. Further research is needed to explore in more detail how efficiency
      is achieved in practice.

PMID- 22473950
TI  - Subjective quality of life of women with intellectual disabilities: the role of
      perceived control over their own life in self-determined behaviour.
AB  - BACKGROUND: Quality of life for people with intellectual disabilities has been
      reported in the research literature across differing demographics. There has
      been, however, little research that has examined in-depth the experiences of
      women with intellectual disabilities aged 40 years or older. MATERIALS AND
      METHODS: Fifty-five women from Sydney, Australia, and Prague, Czech Republic,
      were recruited to the study. Participants were recruited through agencies known
      to the researchers, ensuring ethical conduct of all procedures. RESULTS: Each
      participant completed a semi-structured interview, and using a grounded theory
      approach, a series of themes were identified common across all women. The
      strongest theme identified throughout the interviews was the lack of control
      participants perceived they had over their lives. CONCLUSIONS: The results of
      this study further the call for people with intellectual disabilities to be
      provided the opportunity to participate in decisions about their life choices.

PMID- 22473951
TI  - Screening for intellectual disability in children: a review of the literature.
AB  - BACKGROUND: Early identification of possible intellectual disability can help
      children and families access appropriate services and support more quickly. There
      has been an increasing interest in the use of screening tools for this purpose.
      This study reviews the literature in relation to such tools. METHODS: A
      literature search was carried out for English language articles from 1990 to 2009
      using a range of databases. Secondary searches were carried out from references
      of relevant articles. RESULTS: Only one article was identified which examined the
      ability of an assessment to specifically identify children with a potential
      intellectual disability; however, no information was provided about sensitivity,
      specificity or cut-off points. CONCLUSIONS: There is not, as yet, a screening
      tool that can reliably identify children with a probable intellectual disability.
      Further research in this area is needed.

PMID- 22473952
TI  - Carers' responses to challenging behaviour: a comparison of responses to named
      and unnamed vignettes.
AB  - BACKGROUND: The evidence supporting the application of Weiner's motivational
      model of helping to the behaviour of carers' of people with intellectual
      disabilities and challenging behaviour is inconsistent. One suggested reason for
      this is that many studies use stimuli that might generate different responses
      from those to actual instances of behaviour of real people. METHOD: Sixty-two
      paid carers of people with intellectual disabilities reported attributions,
      emotions and intended behavioural responses to behaviour presented by an unnamed
      person and the same behaviour presented by a named and known person. They also
      completed a scale of behavioural knowledge. RESULTS: Carers make more internal
      and global attributions and identify themselves as less optimistic in response to
      vignettes relating to named and known people than those relating to unnamed
      people. However, data from both unnamed and named vignettes are consistent in
      supporting Weiner's motivational model of helping in demonstrating a mediated
      model for controllability, anger and helping intention. CONCLUSIONS: Unnamed
      vignettes may underestimate the intensity of carers' responses to challenging
      behaviour; however, this study does not provide evidence that there are
      qualitative differences in the interrelationships between variables in data sets
      obtained from unnamed and named vignettes.

PMID- 22473953
TI  - MUTYH gene expression and alternative splicing in controls and polyposis
      patients.
AB  - Mutational loss of the human DNA repair gene MUTYH in the germline predisposes
      for colorectal polyposis and cancer, a recessively heritable disease called MUTYH
      associated polyposis. The MUTYH gene shows heavy alternative splicing, but the
      transcripts relevant for biological function and cancer prevention have not been
      determined. This knowledge is required to assess the consequences that germline
      variants of unknown functional significance may have. We therefore quantified
      expression and investigated patterns of alternative splicing in control
      individuals, tissue samples, and carriers of two frequent germline alterations.
      MUTYH expression differed organ dependently, correlating with proliferative
      activity. Alternative first exons were used tissue specifically; transcripts for
      mitochondrial proteins predominated in muscle tissues, while ascending colon and
      testes showed the highest fractions of transcripts for nuclear proteins. Colon
      cancer cell lines produced predominant transcripts for nuclear protein. Exon
      skipping was frequent and governed by splice-site quality. Five transcripts were
      found to encode the biologically relevant products of the MUTYH gene. Carriers of
      the disease-causing mutation c.1187G>A (p.Gly396Asp) showed normal transcript
      composition, but the frequent single-nucleotide polymorphism rs3219468:G>C
      largely reduced one transcript species of MUTYH. Since this alteration decreases
      protein production of the gene, an increased cancer risk for compound
      heterozygous carriers is possible.

PMID- 22473954
TI  - Advances in copper-catalyzed C-C coupling reactions and related domino reactions
      based on active methylene compounds.
AB  - Active methylene compounds are a major class of reaction partners for C-C bond
      formation with sp(2) C-X (X = halide) fragments. As one of the most-classical
      versions of the Ullmann-type coupling reaction, activated-methylene-based C-C
      coupling reactions have been efficiently employed in a large number of syntheses.
      Although this type of reaction has long relied on noble-metal catalysis, the
      renaissance of copper catalysis at the end of last century has led to dramatic
      developments in Ullmann C-C coupling reactions. Owing to its low cost, abundance,
      as well as excellent catalytic activity, the exceptional atom economy of copper
      catalysis is gaining widespread attention in various organic synthesis. This
      review summarizes the advances in copper-catalyzed intermolecular and
      intramolecular C-C coupling reactions that use activated methylene species as
      well as in tandem reactions that are initiated by this transformation.

PMID- 22473955
TI  - Cockayne syndrome group B protein prevents the accumulation of damaged
      mitochondria by promoting mitochondrial autophagy.
AB  - Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized
      by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are
      caused by mutations in the CS complementation group B (CSB) gene known to be
      involved in DNA repair and transcription. Recent evidence indicates that CSB is
      present in mitochondria, where it associates with mitochondrial DNA (mtDNA). We
      report an increase in metabolism in the CSB(m/m) mouse model and CSB-deficient
      cells. Mitochondrial content is increased in CSB-deficient cells, whereas
      autophagy is down-regulated, presumably as a result of defects in the recruitment
      of P62 and mitochondrial ubiquitination. CSB-deficient cells show increased free
      radical production and an accumulation of damaged mitochondria. Accordingly,
      treatment with the autophagic stimulators lithium chloride or rapamycin reverses
      the bioenergetic phenotype of CSB-deficient cells. Our data imply that CSB acts
      as an mtDNA damage sensor, inducing mitochondrial autophagy in response to
      stress, and that pharmacological modulators of autophagy are potential treatment
      options for this accelerated aging phenotype.

PMID- 22473956
TI  - Essential role of EBF1 in the generation and function of distinct mature B cell
      types.
AB  - The transcription factor EBF1 is essential for lineage specification in early B
      cell development. In this study, we demonstrate by conditional mutagenesis that
      EBF1 is required for B cell commitment, pro-B cell development, and subsequent
      transition to the pre-B cell stage. Later in B cell development, EBF1 was
      essential for the generation and maintenance of several mature B cell types.
      Marginal zone and B-1 B cells were lost, whereas follicular (FO) and germinal
      center (GC) B cells were reduced in the absence of EBF1. Activation of the B cell
      receptor resulted in impaired intracellular signaling, proliferation and survival
      of EBF1-deficient FO B cells. Immune responses were severely reduced upon Ebf1
      inactivation, as GCs were formed but not maintained. ChIP- and RNA-sequencing of
      FO B cells identified EBF1-activated genes that encode receptors, signal
      transducers, and transcriptional regulators implicated in B cell signaling.
      Notably, ectopic expression of EBF1 efficiently induced the development of B-1
      cells at the expense of conventional B cells. These gain- and loss-of-function
      analyses uncovered novel important functions of EBF1 in controlling B cell
      immunity.

PMID- 22473957
TI  - The hypoxia imaging agent CuII(atsm) is neuroprotective and improves motor and
      cognitive functions in multiple animal models of Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive, chronic disease characterized by
      dyskinesia, rigidity, instability, and tremors. The disease is defined by the
      presence of Lewy bodies, which primarily consist of aggregated alpha-synuclein
      protein, and is accompanied by the loss of monoaminergic neurons. Current
      therapeutic strategies only give symptomatic relief of motor impairment and do
      not address the underlying neurodegeneration. Hence, we have identified
      Cu(II)(atsm) as a potential therapeutic for PD. Drug administration to four
      different animal models of PD resulted in improved motor and cognition function,
      rescued nigral cell loss, and improved dopamine metabolism. In vitro, this
      compound is able to inhibit the effects of peroxynitrite-driven toxicity,
      including the formation of nitrated alpha-synuclein oligomers. Our results show
      that Cu(II)(atsm) is effective in reversing parkinsonian defects in animal models
      and has the potential to be a successful treatment of PD.

PMID- 22473958
TI  - ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol
      induced lipid body formation.
AB  - Atherosclerosis is a chronic inflammatory disease characterized by the
      accumulation of lipid-loaded macrophages in the arterial wall. We demonstrate
      that macrophage lipid body formation can be induced by modified lipoproteins or
      by inflammatory Toll-like receptor agonists. We used an unbiased approach to
      study the overlap in these pathways to identify regulators that control foam cell
      formation and atherogenesis. An analysis method integrating epigenomic and
      transcriptomic datasets with a transcription factor (TF) binding site prediction
      algorithm suggested that the TF ATF3 may regulate macrophage foam cell formation.
      Indeed, we found that deletion of this TF results in increased lipid body
      accumulation, and that ATF3 directly regulates transcription of the gene encoding
      cholesterol 25-hydroxylase. We further showed that production of 25
      hydroxycholesterol (25-HC) promotes macrophage foam cell formation. Finally,
      deletion of ATF3 in Apoe(-/-) mice led to in vivo increases in foam cell
      formation, aortic 25-HC levels, and disease progression. These results define a
      previously unknown role for ATF3 in controlling macrophage lipid metabolism and
      demonstrate that ATF3 is a key intersection point for lipid metabolic and
      inflammatory pathways in these cells.

PMID- 22473960
TI  - Dynamics of diffusivity and pressure drop in flow-through and parallel-flow
      bioreactors during tissue regeneration.
AB  - In this study, transport characteristics in flow-through and parallel-flow
      bioreactors used in tissue engineering were simulated using computational fluid
      dynamics. To study nutrient distribution and consumption by smooth muscle cells
      colonizing the 100 mm diameter and 2-mm thick scaffold, effective diffusivity of
      glucose was experimentally determined using a two-chambered setup. Three
      different concentrations of chitosan-gelatin scaffolds were prepared by freezing
      at -80 degrees C followed by lyophilization. Experiments were performed in both
      bioreactors to measure pressure drop at different flow rates. At low flow rates,
      experimental results were in agreement with the simulation results for both
      bioreactors. However, increase in flow rate beyond 5 mL/min in flow-through
      bioreactor showed channeling at the circumference resulting in lower pressure
      drop relative to simulation results. The Peclet number inside the scaffold
      indicated nutrient distribution within the flow-through bioreactor to be
      convection-dependent, whereas the parallel-flow bioreactor was diffusion
      dependent. Three alternative design modifications to the parallel-flow were made
      by (i) introducing an additional inlet and an outlet, (ii) changing channel
      position, and (iii) changing the hold-up volume. Simulation studies were
      performed to assess the effect of scaffold thickness, cell densities, and
      permeability. These new designs improved nutrient distribution for 2 mm
      scaffolds; however, parallel-flow configuration was found to be unsuitable for
      scaffolds more than 4-mm thick, especially at low porosities as tissues
      regenerate. Furthermore, operable flow rate in flow-through bioreactors is
      constrained by the mechanical strength of the scaffold. In summary, this study
      showed limitations and differences between flow-through and parallel-flow
      bioreactors used in tissue engineering.

PMID- 22473962
TI  - Scaling up support for children with developmental disabilities in low- and
      middle-income countries.

PMID- 22473959
TI  - Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and
      leukemia.
AB  - Notch plays critical roles in both cell fate decisions and tumorigenesis. Notch
      receptor engagement initiates signaling cascades that include a
      phosphatidylinositol 3-kinase/target of rapamycin (TOR) pathway. Mammalian TOR
      (mTOR) participates in two distinct biochemical complexes, mTORC1 and mTORC2, and
      the relationship between mTORC2 and physiological outcomes dependent on Notch
      signaling is unknown. In this study, we report contributions of mTORC2 to thymic
      T-cell acute lymphoblastic leukemia (T-ALL) driven by Notch. Conditional deletion
      of Rictor, an essential component of mTORC2, impaired Notch-driven proliferation
      and differentiation of pre-T cells. Furthermore, NF-kappaB activity depended on
      the integrity of mTORC2 in thymocytes. Active Akt restored NF-kappaB activation,
      a normal rate of proliferation, and differentiation of Rictor-deficient pre-T
      cells. Strikingly, mTORC2 depletion lowered CCR7 expression in thymocytes and
      leukemic cells, accompanied by decreased tissue invasion and delayed mortality in
      T-ALL driven by Notch. Collectively, these findings reveal roles for mTORC2 in
      promoting thymic T cell development and T-ALL and indicate that mTORC2 is crucial
      for Notch signaling to regulate Akt and NF-kappaB.

PMID- 22473963
TI  - The identification of children with, or at significant risk of, intellectual
      disabilities in low- and middle-income countries: a review.
AB  - BACKGROUND: Developmental monitoring of children is an important strategy for the
      early detection and management of intellectual disabilities (ID) in high-income
      countries. This review summarizes the literature on identifying children with ID
      in low- and middle-income (LAMI) countries. MATERIALS AND METHODS: Electronic
      literature database searches were conducted to identify articles in the English
      language published since 1990 relating to the identification of children with, or
      at risk of, ID in LAMI countries. Requests for information were also sent to the
      membership of International Association for the Scientific Study of Intellectual
      Disabilities and relevant organizations in selected LAMI countries. RESULTS: A
      total of 37 articles were identified for inclusion in the review, the majority of
      which concerned validation of specific screening tools. Information is presented
      on sensitivity, specificity, positive predictive value, negative predictive value
      and reliability of identified screening tools. CONCLUSION: Studies were mainly
      concerned with identifying child disability. Research and development should
      develop specific approaches to identifying ID among children in LAMI countries.

PMID- 22473964
TI  - Interventions for children with pervasive developmental disorders in low and
      middle income countries.
AB  - BACKGROUND: Although interventions for children with pervasive developmental
      disorders (PDD) have been the focus of research effort and evidence reviews in
      many Western countries, this evidence has not been assessed in the context of low
      and middle-income (LAMI) countries especially in terms of the fit with different
      cultures and resources. METHOD: As a part of the WHO MH-GAP project, we carried
      out a systematic review of published literature relating to interventions for PDD
      in LAMI countries. Given the small amount of direct evidence found, we
      supplemented the review with findings from existing relevant evidence reviews to
      draw practical recommendations. RESULTS: We found only four controlled studies
      evaluating an intervention for children with PDD in a LAMI country. These studies
      all evaluated different interventions. A systematic search of controlled studies
      of evidence-based parenting training interventions (Incredible Years and Triple
      P) in non-LAMI countries identified two studies both indicating successful
      outcomes. CONCLUSIONS: The evidence base for interventions for PDDs in LAMI
      countries is sparse, and to inform practical and future research recommendations,
      it is important to consider potentially deliverable behavioural parent training
      interventions. Such interventions need to be explored in LAMI countries when
      delivered in primary and secondary healthcare contexts.

PMID- 22473965
TI  - Interventions provided by parents for children with intellectual disabilities in
      low and middle income countries.
AB  - BACKGROUND: In low- and middle-income (LAMI) countries, there is a lack of well
      trained therapists to provide specialist interventions for children with
      intellectual disabilities and their families. We sought to identify strategies
      deliverable by families or non-specialist workers. MATERIALS AND METHODS: After
      searches of appropriate scientific databases, we applied GRADE methodology to
      rate the quality of evidence for these interventions. RESULTS: We identified
      small-scale interventions trialled in LAMI countries with limited evidence of
      effectiveness in supporting development, adaptive behaviour and/or community
      participation. In high-income countries, the Stepping Stones Triple P program for
      adaptive behaviour and the Portage program for child development have the most
      extensive evidence base and may be applicable in LAMI countries. CONCLUSIONS:
      There is reason to hope that, when combined with community development
      strategies, the welfare of children with intellectual disabilities in LAMI
      countries can be advanced within those countries' economic means.

PMID- 22473966
TI  - Efficacy of community-based rehabilitation for children with or at significant
      risk of intellectual disabilities in low- and middle-income countries: a review.
AB  - BACKGROUND: Community-based rehabilitation (CBR) is being implemented in more
      than 90 countries. Concerns have been voiced about the adequacy of the evidence
      base regarding the efficacy, effectiveness and efficiency of CBR. This review
      summarizes evidence on the efficacy of CBR for children with intellectual
      disabilities. MATERIALS AND METHOD: Electronic literature database searches were
      conducted to identify articles in the English language published since 1980
      relating to the efficacy of CBR for children with intellectual disabilities.
      Requests for information were also sent to membership of International
      Association for the Scientific Study of Intellectual Disabilities and relevant
      organizations in selected low- and middle-income countries. RESULTS: Thirteen
      studies were identified for inclusion in the review. The quality of evidence for
      the efficacy of CBR for children with intellectual disabilities was 'very low'.
      CONCLUSION: Improving the evidence base will require greater investment in
      evaluation and addressing the marginalization of people with intellectual
      disabilities in CBR.

PMID- 22473967
TI  - Reporting of health problems and pain by adults with an intellectual disability
      and by their carers.
AB  - BACKGROUND: Information about the health of people with ID is usually obtained
      from professionals and carers. Little is known about what health problems people
      with ID report they experience, and whether this differs from their carers'
      reports. METHOD: A secondary analysis of health information provided by
      participants with ID and/or their matched carers as part of a health intervention
      RCT using inclusive methodology. RESULTS: Health information from 98 participants
      with ID is presented. Less than three quarters of participants said they had
      someone to talk to about their health (68/93). Pain was reported by 67% (66/98)
      with 18% (17/95) saying they did not tell anyone when in pain, and 27% (26/97)
      they did not take pain relief medication. Matched carer data for 59 participants
      indicated similar numbers of health problems reported by participants as by their
      carers when prompted with specific problems. Participants reported more headaches
      and allergies, but fewer weight problems than their carers. Concordance was poor
      for many problems. CONCLUSION: Participants reported experiencing a lot of health
      and mental health problems including pain. This information from adults with ID
      is rarely collected, either in research or in routine clinical practice.

PMID- 22473968
TI  - Stigma, social comparison and self-esteem in adults with an intellectual
      disability.
AB  - BACKGROUND: The paper examines the perception of stigma in 43 adults with an
      intellectual disability, the relationship this has with their psychological well
      being and whether the process of social comparison has a moderating effect on
      this relationship. MATERIALS AND METHODS: A questionnaire-based, within
      participant design was used. Participants completed three self-report measures of
      perception of stigma, self-esteem and social comparison. RESULTS: Perception of
      stigma was found to be significantly related to negative social comparisons,
      which in turn was significantly related to low self-esteem. No difference was
      found between social comparisons made with other service users and those made
      with people in the community. Social comparison was not found to have a
      moderating effect on the relationship between stigma and self-esteem. CONCLUSION:
      This study provides support for the influence of the perception of stigma and
      social comparison on the self-concept of individuals with an intellectual
      disability.

PMID- 22473969
TI  - Public attitudes towards people with intellectual disabilities: a qualitative
      comparison of white British & South Asian people.
AB  - BACKGROUND: National and international polices promote the acceptance,
      integration and inclusion of people with intellectual disabilities into
      mainstream society. However, there is little systematic research into general
      population attitudes towards people with intellectual disabilities, and even less
      research, which considers the impact of culture on attitudes. The aim of this
      study was to explore how young people from White British and South Asian
      backgrounds differ in their attitudes towards people with intellectual
      disabilities and above all, how they arrive at their beliefs. MATERIALS AND
      METHOD: A qualitative design utilizing focus groups and individual interviews
      with White British and South Asian adolescents aged 16-19 years (N = 61) was
      employed. Questionnaire data were collected to compare this sample to findings
      from a larger study run concurrently (Attitudes to people with intellectual
      disabilities: a cross cultural study. Thesis, University College London).
      Interview and focus group data were analysed using thematic analysis. RESULTS:
      Thematic analysis yielded five themes and pointed to widespread confusion about
      the concept of 'intellectual disability', not helped by the continuing
      invisibility of people with intellectual disabilities in the media. Participants
      expressed many positive beliefs, yet closer analysis revealed that underlying
      these may be more ambivalent or even hostile attitudes. Key differences between
      the two cultural groups are discussed. CONCLUSIONS: The findings highlight the
      need for raising public awareness and the importance of culturally sensitive
      support.

PMID- 22473971
TI  - Elucidation of pi-conjugation modes in diarene-fused 1,2-dihydro-1,2-diborin
      dianions.
AB  - A series of diarene-fused 1,2-dihydro-1,2-diborins were prepared as a new B-B
      bond-embedded polycyclic pi-electron system. The reduction of these compounds
      with metals produced their corresponding dianions, the pi-conjugation modes of
      which varied from 6pi-conjugation within the central 1,2-diborin skeleton to 14pi
      peripheral conjugation over the tricyclic skeleton, depending on the nature of
      the reduced biaryl framework. Moreover, the countercation to the dianions had a
      significant effect on the absorption spectra, with a dramatic color change from
      yellow to deep blue, depending on the distance between the tricyclic dianion
      skeleton and the countercation.

PMID- 22473970
TI  - A diagnostic genetic test for the physical mapping of germline rearrangements in
      the susceptibility breast cancer genes BRCA1 and BRCA2.
AB  - The BRCA1 and BRCA2 genes are involved in breast and ovarian cancer
      susceptibility. About 2 to 4% of breast cancer patients with positive family
      history, negative for point mutations, can be expected to carry large
      rearrangements in one of these two genes. We developed a novel diagnostic genetic
      test for the physical mapping of large rearrangements, based on molecular combing
      (MC), a FISH-based technique for direct visualization of single DNA molecules at
      high resolution. We designed specific Genomic Morse Codes (GMCs), covering the
      exons, the noncoding regions, and large genomic portions flanking both genes. We
      validated our approach by testing 10 index cases with positive family history of
      breast cancer and 50 negative controls. Large rearrangements, corresponding to
      deletions and duplications with sizes ranging from 3 to 40 kb, were detected and
      characterized on both genes, including four novel mutations. The nature of all
      the identified mutations was confirmed by high-resolution array comparative
      genomic hybridization (aCGH) and breakpoints characterized by sequencing. The
      developed GMCs allowed to localize several tandem repeat duplications on both
      genes. We propose the developed genetic test as a valuable tool to screen large
      rearrangements in BRCA1 and BRCA2 to be combined in clinical settings with an
      assay capable of detecting small mutations.

PMID- 22473972
TI  - Graft loss and racial mismatch in hepatitis C virus-positive liver transplant
      patients.

PMID- 22473974
TI  - Quality attributes of recombinant therapeutic proteins: an assessment of impact
      on safety and efficacy as part of a quality by design development approach.
AB  - Quality by Design (QbD) is a new approach to the development of recombinant
      therapeutic protein products that promotes a better understanding of the product
      and its manufacturing process. The first step in the QbD approach consists in
      identifying the critical quality attributes (CQA), i.e., those quality attributes
      of the product that have an impact on its clinical efficacy or safety. CQAs are
      identified through a science-based risk assessment taking into consideration a
      combination of clinical and nonclinical data obtained with the molecule or other
      similar molecules or platform products, as well as the published literature. The
      purpose of this article is to perform a comprehensive review of the published
      literature, supporting an assessment of the impact on safety and efficacy of the
      quality attributes commonly encountered in recombinant therapeutic proteins, more
      specifically those produced in mammalian cell expression systems. Quality
      attributes generally observed in biopharmaceutical proteins including product
      related impurities and substances, process-related impurities, product
      attributes, and contaminants are evaluated one by one for their impact on
      biological activity, pharmacokinetics and pharmacodynamics, immunogenicity, and
      overall safety/toxicity.

PMID- 22473975
TI  - The rare peat moss Sphagnum wulfianum (Sphagnaceae) did not survive the last
      glacial period in northern European refugia.
AB  - PREMISE OF THE STUDY: Organisms may survive unfavorable conditions either by
      moving to more favorable areas by means of dispersal or by adapting to stressful
      environments. Pleistocene glacial periods represent extremely unfavorable
      conditions for the majority of life forms, especially sessile organisms. Many
      studies have revealed placements of refugial areas and postglacial colonization
      patterns of seed plants, but little is still known about areas of long-term
      survival and historical migration routes of bryophytes. Given overall differences
      in stress tolerance between seed plants and bryophytes, it is of interest to know
      whether bryophytes have survived periods of extreme climatic conditions better
      then seed plants in northern areas. METHODS: The haploid and rarely spore
      producing peat moss Sphagnum wulfianum is mostly found in areas that were covered
      by ice during the last glacial maximum. Twelve microsatellite markers were
      amplified from 43 populations (367 shoots) of this species, and data were
      analyzed using population genetic diversity statistics, Bayesian clustering
      methods, and coalescence-based inference tools to estimate historical and
      demographic parameters. KEY RESULTS: Genetic diversity within populations was
      low, but populations were highly differentiated, with two main genetic clusters
      being recognized. CONCLUSION: The two main genetic groups have diverged quite
      recently in the Holocene, and the pattern of genetic variability and structuring
      gives no support for survival in Scandinavian refugia during the last glacial
      period in this species. The dispersal ability of this plant thus seems
      surprisingly high despite its infrequent spore production.

PMID- 22473973
TI  - Prenatal immune challenge in rats: altered responses to dopaminergic and
      glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route
      based learning as a function of maternal body weight gain after prenatal exposure
      to poly IC.
AB  - Prenatal maternal immune activation has been used to test the neurodevelopmental
      hypothesis of schizophrenia. Most of the data are in mouse models; far less is
      available for rats. We previously showed that maternal weight change in response
      to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats
      differentially affects offspring. Therefore, we treated gravid Harlan Sprague
      Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly
      IC group was divided into those that lost or gained the least weight, Poly IC
      (L), versus those that gained the most weight, Poly IC (H), following treatment.
      The study design controlled for litter size, litter sampling, sex distribution,
      and test experience. We found no effects of Poly IC on elevated zero maze, open
      field activity, object burying, light-dark test, straight channel swimming,
      Morris water maze spatial acquisition, reversal, or shift navigation or spatial
      working or reference memory, or conditioned contextual or cued fear or latent
      inhibition. The Poly IC (H) group showed a significant decrease in the rate of
      route-based learning when visible cues were unavailable in the Cincinnati water
      maze and reduced prepulse inhibition of acoustic startle in females, but not
      males. The Poly IC (L) group exhibited altered responses to acute pharmacological
      challenges: exaggerated hyperactivity in response to (+)-amphetamine and an
      attenuated hyperactivity in response to MK-801. This model did not exhibit the
      cognitive, or latent inhibition deficits reported in Poly IC-treated rats but
      showed changes in response to drugs acting on neurotransmitter systems implicated
      in the pathophysiology of schizophrenia (dopaminergic hyperfunction and
      glutamatergic hypofunction).

PMID- 22473976
TI  - Genetic diversity and differentiation of core vs. peripheral populations of
      eastern white cedar, Thuja occidentalis (Cupressaceae).
AB  - PREMISE OF THE STUDY: Geographically peripheral (marginal) populations are
      expected to have lower genetic diversity and higher genetic differentiation than
      geographically core (central) populations as a result of supposedly lower
      effective population size (N(e)) and higher genetic drift, founder effect,
      fragmentation, and isolation in peripheral than in core populations. Here we
      address this issue for a long-lived plant species, eastern white cedar (Thuja
      occidentalis). METHODS: Genetic diversity and population structure of 13 natural
      populations of eastern white cedar from its Canadian eastern peripheral and core
      natural ranges in New Brunswick, Nova Scotia, and Prince Edward Island were
      studied using six nuclear microsatellite DNA markers. KEY RESULTS: The core
      populations of eastern white cedar had significantly higher allelic diversity
      (mean A = 8.83, A(r) = 8.13, A(e) = 4.03) and N(e) (428) than the peripheral
      populations (A = 6.64, A(r) = 6.15, A(e) = 3.12, N(e) = 198). However, expected
      heterozygosity was similar in the core (H(e) = 0.64) and peripheral (H(e) = 0.60)
      populations. Genetic differentiation was significantly higher among the
      peripheral (F(ST) = 0.089) than among the core (F(ST) = 0.032) populations. No
      genetic differentiation (F(ST)/Phi(RT) = 0.000) was detected between core and
      peripheral regions. CONCLUSIONS: Peripheral populations have significantly lower
      N(e) and genetic diversity in terms of allelic diversity (richness) and
      significantly higher genetic differentiation than the core populations of eastern
      white cedar in its Canadian eastern range. However, core and peripheral
      populations have similar levels of expected heterozygosity. Implications for
      conservation of eastern white cedar genetic resources are discussed.

PMID- 22473977
TI  - Molecular phylogenetics of Hydatellaceae (Nymphaeales): sexual-system homoplasy
      and a new sectional classification.
AB  - PREMISE OF THE STUDY: Species relationships are unknown in Hydatellaceae, a small
      family of dwarf aquatics related to water lilies that arose near the base of
      angiosperm phylogeny. Here we use molecular evidence to infer a species tree for
      the family and apply this to reconstructing major transitions in morphology and
      sexual system in this early branch of angiosperms. METHODS: We assembled plastid
      (atpB, matK, ndhF, rbcL) and nuclear (ribosomal ITS) data for 50 samples
      (including outgroups) and estimated a species tree for Hydatellaceae using a
      Bayesian multispecies coalescent approach. We reconstructed the evolution of
      several morphological characters, then tested for associations between sexual
      system and reproductive morphology using phylogenetic ANOVA. KEY RESULTS:
      Dioecious species of Hydatellaceae have significantly greater stamen number and
      anther length than do cosexual species, suggesting changes in male function. The
      perennial habit that defines one subclade likely represents a reversion from
      annuality. Species relationships do not fall along traditional morphological
      divisions, but new sections proposed here are supported by fruit and seed
      synapomorphies. The earliest split in the family is reflected in geography and
      climate (i.e., tropical vs. subtropical/temperate clades). We found limited
      evidence of incongruence between plastid and nuclear trees, with one exception
      involving gene-tree nonmonophyly for two close relatives (Trithuria submersa, T.
      bibracteata). CONCLUSIONS: While the direction of sexual-system evolution is
      ambiguous, transitions are significantly associated with changes in involucral
      phyllome length and proxies of pollen production. We propose a new sectional
      circumscription based on fruit, seed, and DNA evidence.

PMID- 22473978
TI  - Evidence of reduced arbuscular mycorrhizal fungal colonization in multiple lines
      of Bt maize.
AB  - PREMISE OF THE STUDY: Insect-resistant Bacillus thuringiensis (Bt) maize is
      widely cultivated, yet few studies have examined the interaction of symbiotic
      arbuscular mycorrhizal fungi (AMF) with different lines of Bt maize. As obligate
      symbionts, AMF may be sensitive to genetic changes within a plant host. Previous
      evaluations of the impact of Bt crops on AMF have been inconsistent, and because
      most studies were conducted under disparate experimental conditions, the results
      are difficult to compare. METHODS: We evaluate AMF colonization in nine Bt maize
      lines, differing in number and type of engineered trait, and five corresponding
      near-isogenic parental (P) base hybrids in greenhouse microcosms. Plants were
      grown in 50% local agricultural soil with low levels of fertilization, and AMF
      colonization was evaluated at 60 and 100 d. Nontarget effects of Bt cultivation
      on AMF colonization were tested in a subsequently planted crop, Glycine max,
      which was seeded into soil that had been preconditioned for 60 d with Bt or P
      maize. KEY RESULTS: We found that Bt maize had lower levels of AMF colonization
      in their roots than did the non-Bt parental lines. However, reductions in AMF
      colonization were not related to the expression of a particular Bt protein. There
      was no difference in AMF colonization in G. max grown in the Bt- or P
      preconditioned soil. CONCLUSIONS: These findings are the first demonstration of a
      reduction in AMF colonization in multiple Bt maize lines grown under the same
      experimental conditions and contribute to the growing body of knowledge examining
      the unanticipated effects of Bt crop cultivation on nontarget soil organisms.

PMID- 22473979
TI  - Microsatellite markers isolated from the wild medicinal plant Centella asiatica
      (Apiaceae) from an enriched genomic library.
AB  - PREMISE OF THE STUDY: Microsatellite markers for Centella asiatica, an important
      medicinal herb, were developed and characterized to promote genetic and molecular
      studies. METHODS AND RESULTS: A GA/GT-enriched genomic library was constructed
      from an accession from Madagascar. Roughly 75% of the 768 clones of the enriched
      library contained microsatellites. Eighty sequences containing microsatellites
      were obtained from 96 positive clones. Specific primers were designed for 20
      loci, and 17 of them displayed polymorphism when screened across 17 C. asiatica
      accessions, with an average of 4.3 alleles per locus. The observed and expected
      heterozygosity values averaged 0.114 and 0.379, respectively. CONCLUSIONS: This
      is the first report constructing an enriched genomic library and identifying
      microsatellite markers from C. asiatica. These 17 polymorphic microsatellite
      markers are a useful resource for this plant, applicable for diversity studies,
      pedigree analyses, and genetic mapping.

PMID- 22473980
TI  - Development and characterization of microsatellite markers for the wild South
      American Passiflora cincinnata (Passifloraceae).
AB  - PREMISE OF THE STUDY: We developed the first set of microsatellite markers for
      the passion fruit, Passiflora cincinnata, to provide tools for further study of
      its genetic diversity and to support current conservation and genetic studies.
      METHODS AND RESULTS: We used a microsatellite-enriched library approach to
      isolate and characterize 25 new molecular markers. Seven primer pairs
      successfully amplified polymorphic microsatellite regions, with an average of
      five alleles per locus. The mean values of expected and observed levels of
      heterozygosity were 0.516 and 0.525, respectively. CONCLUSIONS: The
      microsatellite markers identified in this study may be valuable tools for
      population genetic studies, and this set of markers also may be useful in the
      design of a genetic conservation strategy, mating system, and hybridization
      studies.

PMID- 22473981
TI  - Microsatellite development for an endangered riparian inhabitant, Lilaeopsis
      schaffneriana subsp. recurva (Apiaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed and characterized to
      evaluate genetic diversity and population structure in Lilaeopsis schaffneriana
      subsp. recurva, an endangered species endemic to wetlands dispersed throughout
      southeastern Arizona, USA, and northern Sonora, Mexico. METHODS AND RESULTS:
      Eight loci (one of which was monomorphic) were developed and characterized in 48
      individuals from two populations. The total number of alleles was 35, ranging
      from one to 10 per locus. Many of the primers amplified in L. carolinensis, L.
      chinensis, L. masonii, L. occidentalis, L. schaffneriana subsp. schaffneriana,
      Oxypolis fendleri, and Eryngium lemmonii. CONCLUSIONS: Development of these novel
      microsatellite loci will facilitate a deeper understanding of genetic diversity,
      mode of reproduction, and population structure not only in L. schaffneriana
      subsp. recurva, but also in apiaceous relatives.

PMID- 22473982
TI  - Development and characterization of microsatellite markers for Emmenopterys
      henryi (Rubiaceae), a rare tree from China.
AB  - PREMISE OF THE STUDY: Compound microsatellite primers were developed for
      Emmenopterys henryi, an endangered deciduous tree endemic to China, to assess its
      genetic diversity and population structure as well as its evolutionary history.
      METHODS AND RESULTS: Using the compound microsatellite marker technique, 10 pairs
      of polymorphic microsatellite primers were isolated and characterized in E.
      henryi. Levels of polymorphism were tested across a total of 63 individuals from
      three natural populations. Allele numbers varied from 10 to 20 per locus, with an
      average of 14.50 alleles per locus. The observed heterozygosity per locus ranged
      from 0.125 to 0.962, and the expected heterozygosity ranged from 0.377 to 0.903.
      CONCLUSIONS: The highly polymorphic markers developed and characterized in this
      study will facilitate evolutionary and population genetic studies in E. henryi.

PMID- 22473983
TI  - Development of 198 novel EST-derived microsatellites in Eucalyptus (Myrtaceae).
AB  - PREMISE OF THE STUDY: Expressed sequence tag (EST)-derived microsatellites were
      identified in Eucalyptus through screening the GenBank database. The loci were
      sequence-verified and explored for polymorphism among 20 genotypes. METHODS AND
      RESULTS: In total, 198 novel microsatellites were developed from 8262 unigenes,
      with the identity of 73.6-100% to the original sequences and presence of the
      expected repeat motifs. One hundred and eighty-four markers proved to be
      polymorphic among 10 E. urophylla and 10 E. tereticornis genotypes, with the
      number of alleles per locus, observed heterozygosity, and polymorphic information
      content being 2-17 (mean: 7.11), 0-1.0 (mean: 0.4511), and 0.0940-0.9131 (mean:
      0.6571), respectively. CONCLUSIONS: These markers will be useful for germplasm
      characterization, genome mapping, and gene tagging for economic traits in the two
      species examined and may have potential for genetic applications in Eucalyptus.

PMID- 22473984
TI  - Exploring the no-man's land between molecular nanomagnets and magnetic
      nanoparticles.
AB  - The comparison of the structural and magnetic properties of molecular nanomagnets
      (MNM) and magnetic nanoparticles (MNP) can be instructive to get a deeper
      understanding of the magnetic behavior on the intermediate scale between
      molecular and bulk objects. In this respect iron oxo based clusters are
      particularly interesting, since they provide an increasing number of molecular
      systems with sizes close to that of iron oxide MNP. In this Minireview we report
      a survey of literature data aimed at improving our understanding of the emergence
      of MNP properties from MNM ones.

PMID- 22473985
TI  - Overexpression of AtOGG1, a DNA glycosylase/AP lyase, enhances seed longevity and
      abiotic stress tolerance in Arabidopsis.
AB  - Reactive oxygen species (ROS) are toxic by-products generated continuously during
      seed desiccation, storage, and germination, resulting in seed deterioration and
      therefore decreased seed longevity. The toxicity of ROS is due to their
      indiscriminate reactivity with almost any constituent of the cell, such as
      lipids, proteins, and DNA. The damage to the genome induced by ROS has been
      recognized as an important cause of seed deterioration. A prominent DNA lesion
      induced by ROS is 7,8-dihydro-8-oxoguanine (8-oxo-G), which can form base pairs
      with adenine instead of cytosine during DNA replication and leads to GC->TA
      transversions. In Arabidopsis, AtOGG1 is a DNA glycosylase/apurinic/apyrimidinic
      (AP) lyase that is involved in base excision repair for eliminating 8-oxo-G from
      DNA. In this study, the functions of AtOGG1 were elaborated. The transcript of
      AtOGG1 was detected in seeds, and it was strongly up-regulated during seed
      desiccation and imbibition. Analysis of transformed Arabidopsis protoplasts
      demonstrated that AtOGG1-yellow fluorescent protein fusion protein localized to
      the nucleus. Overexpression of AtOGG1 in Arabidopsis enhanced seed resistance to
      controlled deterioration treatment. In addition, the content of 8-hydroxy-2'
      deoxyguanosine (8-oxo-dG) in transgenic seeds was reduced compared to wild-type
      seeds, indicating a DNA damage-repair function of AtOGG1 in vivo. Furthermore,
      transgenic seeds exhibited increased germination ability under abiotic stresses
      such as methyl viologen, NaCl, mannitol, and high temperatures. Taken together,
      our results demonstrated that overexpression of AtOGG1 in Arabidopsis enhances
      seed longevity and abiotic stress tolerance.

PMID- 22473986
TI  - Polar auxin transport: an early invention.
AB  - In higher plants, cell-to-cell polar auxin transport (PAT) of the phytohormone
      auxin, indole-3-acetic acid (IAA), generates maxima and minima that direct growth
      and development. Although IAA is present in all plant phyla, PAT has only been
      detected in land plants, the earliest being the Bryophytes. Charophyta, a group
      of freshwater green algae, are among the first multicellular algae with a land
      plant-like phenotype and are ancestors to land plants. IAA has been detected in
      members of Charophyta, but its developmental role and the occurrence of PAT are
      unknown. We show that naphthylphthalamic acid (NPA)-sensitive PAT occurs in
      internodal cells of Chara corallina. The relatively high velocity (at least 4-5
      cm/h) of auxin transport through the giant (3-5 cm) Chara cells does not occur by
      simple diffusion and is not sensitive to a specific cytoplasmic streaming
      inhibitor. The results demonstrate that PAT evolved early in multicellular plant
      life. The giant Chara cells provide a unique new model system to study PAT, as
      Chara allows the combining of real-time measurements and mathematical modelling
      with molecular, developmental, cellular, and electrophysiological studies.

PMID- 22473987
TI  - Malignant melanoma of the head and neck: a multi-institutional retrospective
      analysis of cases in northern Japan.
AB  - BACKGROUND: Mucosal melanoma of the head and neck is rare and is associated with
      a poor prognoses because of locoregional failure and distant metastasis. The aim
      of our study was to review the characteristics of these patients in northern
      Japan and to analyze their outcomes. METHODS: The medical records of 94 patients
      who had been provided initial treatment in 12 institutes from 1998 to 2007 were
      reviewed. RESULTS: When the 5-year overall survival rates of patients were
      evaluated, we found that the survival rates of patients treated by chemotherapy
      were significantly lower than those of patients treated by surgery or radiation.
      The survival rates of the single-treatment modality, 2-modality, and >=3-modality
      groups were 23.4%, 38.0%, and 33.6%, respectively. CONCLUSION: Our results
      suggest that patients who underwent combined treatment had better prognoses.
      However, we found that chemotherapy had no additional survival benefits.

PMID- 22473988
TI  - 1-Bromo-2-(cyclopropylidenemethyl)benzene: a useful building block in the
      palladium-catalyzed reaction of 2-alkynylbenzenamine.
AB  - A novel palladium-catalyzed domino reaction of 1-bromo-2
      (cyclopropylidenemethyl)benzene and 2-alkynylbenzenamine is reported, which
      generates 2-(naphthalen-2-yl)benzenamines and 5H-indeno[1,2-c]quinolines via 6
      endo and 5-exo cyclization, respectively. The regioselectivity for the final
      outcome can be affected by phosphine and N-heterocyclic carbene ligands.

PMID- 22473989
TI  - DLC1 interaction with alpha-catenin stabilizes adherens junctions and enhances
      DLC1 antioncogenic activity.
AB  - The DLC1 (for deleted in liver cancer 1) tumor suppressor gene encodes a RhoGAP
      protein that inactivates Rho GTPases, which are implicated in regulation of the
      cytoskeleton and adherens junctions (AJs), a cell-cell adhesion protein complex
      associated with the actin cytoskeleton. Malignant transformation and tumor
      progression to metastasis are often associated with changes in cytoskeletal
      organization and cell-cell adhesion. Here we have established in human cells that
      the AJ-associated protein alpha-catenin is a new binding partner of DLC1. Their
      binding was mediated by the N-terminal amino acids 340 to 435 of DLC1 and the N
      terminal amino acids 117 to 161 of alpha-catenin. These proteins colocalized in
      the cytosol and in the plasma membrane, where together they associated with E
      cadherin and beta-catenin, constitutive AJ proteins. Binding of DLC1 to alpha
      catenin led to their accumulation at the plasma membrane and required DLC1 GAP
      activity. Knocking down alpha-catenin in DLC1-positive cells diminished DLC1
      localization at the membrane. The DLC1-alpha-catenin complex reduced the Rho GTP
      level at the plasma membrane, increased E-cadherin's mobility, affected actin
      organization, and stabilized AJs. This process eventually contributed to a robust
      oncosuppressive effect of DLC1 in metastatic prostate carcinoma cells. Together,
      these results unravel a new mechanism through which DLC1 exerts its strong
      oncosuppressive function by positively influencing AJ stability.

PMID- 22473990
TI  - Deep intron elements mediate nested splicing events at consecutive AG
      dinucleotides to regulate alternative 3' splice site choice in vertebrate 4.1
      genes.
AB  - Distal intraexon (iE) regulatory elements in 4.1R pre-mRNA govern 3' splice site
      choice at exon 2 (E2) via nested splicing events, ultimately modulating
      expression of N-terminal isoforms of cytoskeletal 4.1R protein. Here we explored
      intrasplicing in other normal and disease gene contexts and found conservation of
      intrasplicing through vertebrate evolution. In the paralogous 4.1B gene, we
      identified ~120 kb upstream of E2 an ultradistal intraexon, iE(B), that mediates
      intrasplicing by promoting two intricately coupled splicing events that ensure
      selection of a weak distal acceptor at E2 (E2dis) by prior excision of the
      competing proximal acceptor (E2prox). Mutating iE(B) in minigene splicing
      reporters abrogated intrasplicing, as did blocking endogenous iE(B) function with
      antisense morpholinos in live mouse and zebrafish animal models. In a human
      elliptocytosis patient with a mutant 4.1R gene lacking E2 through E4, we showed
      that aberrant splicing is consistent with iE(R)-mediated intrasplicing at the
      first available exons downstream of iE(R), namely, alternative E5 and
      constitutive E6. Finally, analysis of heterologous acceptor contexts revealed a
      strong preference for nested 3' splice events at consecutive pairs of AG
      dinucleotides. Distal regulatory elements may control intrasplicing at a subset
      of alternative 3' splice sites in vertebrate pre-mRNAs to generate proteins with
      functional diversity.

PMID- 22473991
TI  - Fbw7 and p53 cooperatively suppress advanced and chromosomally unstable
      intestinal cancer.
AB  - Colorectal cancer (CRC) remains a major cause of cancer mortality worldwide.
      Murine models have yielded critical insights into CRC pathogenesis, but they
      often fail to recapitulate advanced-disease phenotypes, notably metastasis and
      chromosomal instability (CIN). New models are thus needed to understand disease
      progression and to develop therapies. We sought to model advanced CRC by
      inactivating two tumor suppressors that are mutated in human CRCs, the Fbw7
      ubiquitin ligase and p53. Here we report that Fbw7 deletion alters
      differentiation and proliferation in the gut epithelium and stabilizes oncogenic
      Fbw7 substrates, such as cyclin E and Myc. However, Fbw7 deletion does not cause
      tumorigenesis in the gut. In contrast, codeletion of both Fbw7 and p53 causes
      highly penetrant, aggressive, and metastatic adenocarcinomas, and allografts
      derived from these tumors form highly malignant adenocarcinomas. In vitro
      evidence indicates that Fbw7 ablation promotes genetic instability that is
      suppressed by p53, and we show that most Fbw7-/-; p53-/- carcinomas exhibit a
      CIN+ phenotype. We conclude that Fbw7 and p53 synergistically suppress
      adenocarcinomas that mimic advanced human CRC with respect to histopathology,
      metastasis, and CIN. This model thus represents a novel tool for studies of
      advanced CRC as well as carcinogenesis associated with ubiquitin pathway
      mutations.

PMID- 22473992
TI  - Peroxisome proliferator-activated receptor beta/delta cross talks with E2F and
      attenuates mitosis in HRAS-expressing cells.
AB  - The role of peroxisome proliferator-activated receptor beta/delta
      (PPARbeta/delta) in Harvey sarcoma ras (Hras)-expressing cells was examined.
      Ligand activation of PPARbeta/delta caused a negative selection with respect to
      cells expressing higher levels of the Hras oncogene by inducing a mitotic block.
      Mitosis-related genes that are predominantly regulated by E2F were induced to a
      higher level in HRAS-expressing Pparbeta/delta-null keratinocytes compared to
      HRAS-expressing wild-type keratinocytes. Ligand-activated PPARbeta/delta
      repressed expression of these genes by direct binding with p130/p107,
      facilitating nuclear translocation and increasing promoter recruitment of
      p130/p107. These results demonstrate a novel mechanism of PPARbeta/delta cross
      talk with E2F signaling. Since cotreatment with a PPARbeta/delta ligand and
      various mitosis inhibitors increases the efficacy of increasing G2/M arrest,
      targeting PPARbeta/delta in conjunction with mitosis inhibitors could become a
      suitable option for development of new multitarget strategies for inhibiting RAS
      dependent tumorigenesis.

PMID- 22473993
TI  - LGR5 interacts and cointernalizes with Wnt receptors to modulate Wnt/beta-catenin
      signaling.
AB  - LGR5, a seven-transmembrane domain receptor of the rhodopsin family, is a Wnt
      target gene and a bona fide marker of adult stem cells in the gastrointestinal
      tract and hair follicle bulge. Recently, we and others demonstrated that LGR5 and
      its homologues function as receptors of the R-spondin family of stem cell factors
      to potentiate Wnt/beta-catenin signaling. However, the mechanism of how LGR5
      enhances the signaling output remains unclear. Here we report that following
      costimulation with the ligands R-spondin1 and Wnt3a, LGR5 interacts and forms a
      supercomplex with the Wnt coreceptors LRP6 and Fzd5 which is rapidly internalized
      and then degraded. Internalization of LGR5 is mediated through a dynamin- and
      clathrin-dependent pathway. Inhibition of this endocytic process has no effect on
      LGR5 signaling. Deletion of the C-terminal tail of LGR5 maintains its ability to
      interact with LRP6, yet this LGR5 mutant exhibits increased signaling activity
      and a decreased rate of endocytosis in response to R-spondin1 compared to the
      wild-type receptor. This study provides direct evidence that LGR5 becomes part of
      the Wnt signaling complex at the membrane level to enhance Wnt/beta-catenin
      signaling. However, internalization of LGR5 does not appear to be essential for
      potentiating the canonical Wnt signaling pathway.

PMID- 22473994
TI  - POF regulates the expression of genes on the fourth chromosome in Drosophila
      melanogaster by binding to nascent RNA.
AB  - In Drosophila, two chromosome-wide compensatory systems have been characterized:
      the dosage compensation system that acts on the male X chromosome and the
      chromosome-specific regulation of genes located on the heterochromatic fourth
      chromosome. Dosage compensation in Drosophila is accomplished by
      hypertranscription of the single male X chromosome mediated by the male-specific
      lethal (MSL) complex. The mechanism of this compensation is suggested to involve
      enhanced transcriptional elongation mediated by the MSL complex, while the
      mechanism of compensation mediated by the painting of fourth (POF) protein on the
      fourth chromosome has remained elusive. Here, we show that POF binds to nascent
      RNA, and this binding is associated with increased transcription output from
      chromosome 4. We also show that genes located in heterochromatic regions spend
      less time in transition from the site of transcription to the nuclear envelope.
      These results provide useful insights into the means by which genes in
      heterochromatic regions can overcome the repressive influence of their hostile
      environment.

PMID- 22473995
TI  - Dissociation of cardiogenic and postnatal myocardial activities of GATA4.
AB  - Transcription factor GATA4 is a critical regulator of the embryonic and postnatal
      heart, but the mechanisms and cofactors required for its diverse functions are
      not fully understood. Here, we show that whereas the N-terminal domain of GATA4
      is required for inducing cardiogenesis and for promoting postnatal cardiomyocyte
      survival, distinct residues and domains therein are necessary to mediate these
      effects. Cardiogenic activity of GATA4 requires a 24-amino-acid (aa) region (aa
      129 to 152) which is needed for transcriptional synergy and physical interaction
      with BAF60c. The same region is not essential for induction of endoderm or blood
      cell markers by GATA4, suggesting that it acts as a cell-type-specific
      transcriptional activation domain. On the other hand, a serine residue at
      position 105, which is a known target for mitogen-activated protein kinase (MAPK)
      phosphorylation, is necessary for GATA4-dependent cardiac myocyte survival and
      hypertrophy but is entirely dispensable for GATA4-induced cardiogenesis. We find
      that S105 is differentially required for transcriptional synergy between GATA4
      and serum response factor (SRF) but not other cardiac cofactors such as TBX5 and
      NKX2.5. The findings provide new insight into GATA4 mechanisms of action and
      suggest that distinct regulatory pathways regulate activities of GATA4 in
      embryonic development and postnatal hearts.

PMID- 22473996
TI  - MicroRNA-155 is required for Mycobacterium bovis BCG-mediated apoptosis of
      macrophages.
AB  - Pathogenic mycobacteria, including Mycobacterium tuberculosis and Mycobacterium
      bovis, cause significant morbidity and mortality worldwide. However, the vaccine
      strain Mycobacterium bovis BCG, unlike virulent strains, triggers extensive
      apoptosis of infected macrophages, a step necessary for the elicitation of robust
      protective immunity. We here demonstrate that M. bovis BCG triggers Toll-like
      receptor 2 (TLR2)-dependent microRNA-155 (miR-155) expression, which involves
      signaling cross talk among phosphatidylinositol 3-kinase (PI3K), protein kinase
      Cdelta (PKCdelta), and mitogen-activated protein kinases (MAPKs) and recruitment
      of NF-kappaB and c-ETS to miR-155 promoter. Genetic and signaling perturbations
      presented the evidence that miR-155 regulates PKA signaling by directly targeting
      a negative regulator of PKA, protein kinase inhibitor alpha (PKI-alpha). Enhanced
      activation of PKA signaling resulted in the generation of PKA C-alpha;
      phosphorylation of MSK1, cyclic AMP response element binding protein (CREB), and
      histone H3; and recruitment of phospho-CREB to the apoptotic gene promoters. The
      miR-155-triggered activation of caspase-3, BAK1, and cytochrome c translocation
      involved signaling integration of MAPKs and epigenetic or posttranslational
      modification of histones or CREB. Importantly, M. bovis BCG infection-induced
      apoptosis was severely compromised in macrophages derived from miR-155 knockout
      mice. Gain-of-function and loss-of-function studies validated the requirement of
      miR-155 for M. bovis BCG's ability to trigger apoptosis. Overall, M. bovis BCG
      driven miR-155 dictates cell fate decisions of infected macrophages, strongly
      implicating a novel role for miR-155 in orchestrating cellular reprogramming
      during immune responses to mycobacterial infection.

PMID- 22473997
TI  - Nuclear translocation of type I transforming growth factor beta receptor confers
      a novel function in RNA processing.
AB  - Signaling of transforming growth factor beta (TGF-beta) is redirected in cancer
      to promote malignancy, but how TGF-beta function is altered in a transformed cell
      is not fully understood. We investigated TGF-beta signaling by profiling proteins
      that differentially bound to type I TGF-beta receptor (TbetaRI) in
      nontransformed, HER2-transformed, and HER2-negative breast cancer cells using
      immunoprecipitation followed by protein identification. Interestingly, several
      nuclear proteins implicated in posttranscriptional RNA processing were uniquely
      identified in the TbetaRI coprecipitates from HER2-transformed cells. Ligand
      inducible nuclear translocation of TbetaRI was observed only in transformed
      cells, and the translocation required importin beta1, nucleolin, and Smad2/3.
      This trafficking was dependent on the high Ran GTPase activity resulting from
      oncogenic transformation. In the nucleus, TbetaRI associated with purine-rich RNA
      sequences in a synergistic manner with the RNA-binding factor hnRNP A1. We
      further found that nuclear translocation of TbetaRI specifically induced
      epidermal growth factor receptor (EGFR) transcript isoform c, which encodes a
      soluble EGFR protein, through alternative splicing or 3'-end processing. Our
      study confirms a cancer-specific nuclear translocation of TbetaRI and
      demonstrates its potential function in regulating nuclear RNA processing, as well
      as a novel gain-of-function mechanism of TGF-beta signaling in cancer.

PMID- 22473999
TI  - Porous single-crystalline palladium nanoparticles with high catalytic activities.
AB  - Palladium's pore cousin: a facile approach is described for the size-controlled
      preparation of porous single-crystalline Pd nanoparticles. These porous Pd
      nanoparticles exhibit size-independent catalytic activities for the Suzuki
      coupling and are more active than commercial Pd/C catalysts.

PMID- 22473998
TI  - An Evi1-C/EBPbeta complex controls peroxisome proliferator-activated receptor
      gamma2 gene expression to initiate white fat cell differentiation.
AB  - Fibroblastic preadipocyte cells are recruited to differentiate into new
      adipocytes during the formation and hyperplastic growth of white adipose tissue.
      Peroxisome proliferator-activated receptor gamma (PPARgamma), the master
      regulator of adipogenesis, is expressed at low levels in preadipocytes, and its
      levels increase dramatically and rapidly during the differentiation process.
      However, the mechanisms controlling the dynamic and selective expression of
      PPARgamma in the adipocyte lineage remain largely unknown. We show here that the
      zinc finger protein Evi1 increases in preadipocytes at the onset of
      differentiation prior to increases in PPARgamma levels. Evi1 expression converts
      nonadipogenic cells into adipocytes via an increase in the predifferentiation
      levels of PPARgamma2, the adipose-selective isoform of PPARgamma. Conversely,
      loss of Evi1 in preadipocytes blocks the induction of PPARgamma2 and suppresses
      adipocyte differentiation. Evi1 binds with C/EBPbeta to regulatory sites in the
      Ppargamma locus at early stages of adipocyte differentiation, coincident with the
      induction of Ppargamma2 expression. These results indicate that Evi1 is a key
      regulator of adipogenic competency.

PMID- 22474000
TI  - Tuning complex shapes in platinum nanoparticles: from cubic dendrites to fivefold
      stars.

PMID- 22474001
TI  - Non-destructive staging of barley reproductive development for molecular analysis
      based upon external morphology.
AB  - A prerequisite to study the molecular genetic pathways of pollen and anther
      development is an accurate staging system for reproductive development. However
      in barley, floret formation occurs mainly within the pseudostem, which makes the
      observation of floret development and access to the floret particularly difficult
      without dissecting the plant. Thus selecting stages for molecular analysis cannot
      be done non-destructively. A staging method has therefore been developed for
      barley in order to define the relationship between readily detectable growth
      points and reproductive development, to provide a clear key to enable accurate
      selection of reproductive material. Initial staging followed the traditional
      Zadoks decimal system, with minor adaptations to stages 31-34 and stage 37. The
      later stages, from 37 onward, were replaced by growth staging based upon the last
      flag elongation (LFE) and the position occupied by the spike within the
      pseudostem. Spike size could be readily predicted by using the staging system
      incorporating Zadoks stages 31-37, supplemented with substages and by LFE staging
      to improve accuracy. The different spike sizes, as well as the LFE stages, showed
      a clear relationship to events occurring within the anther, as confirmed by light
      microscopy of the anthers. The defined relationship between spike size and
      development to anther development now makes possible the accurate prediction of
      anther and pollen progression by external staging. This, therefore, provides a
      mechanism for non-destructive selection of material for analysis that is critical
      for the molecular characterization of genes in anther and pollen development.

PMID- 22474002
TI  - Novel molluskan biomineralization proteins retrieved from proteomics: a case
      study with Upsalin.
AB  - The formation of the molluskan shell is regulated by an array of extracellular
      proteins secreted by the calcifying epithelial cells of the mantle. These
      proteins remain occluded within the recently formed biominerals. To date, many
      shell proteins have been retrieved, but only a few of them, such as nacreins,
      have clearly identified functions. In this particular case, by combining
      molecular biology and biochemical approaches, we performed the molecular
      characterization of a novel protein that we named Upsalin, associated with the
      nacreous shell of the freshwater mussel Unio pictorum. The full sequence of the
      upsalin transcript was obtained by RT-PCR and 5'/3' RACE, and the expression
      pattern of the transcript was studied by PCR and qPCR. Upsalin is a 12 kDa
      protein with a basic theoretical pI. The presence of Upsalin in the shell was
      demonstrated by extraction of the acetic-acid-soluble nacre matrix, purification
      of a shell protein fraction by mono-dimensional preparative SDS-PAGE, and by
      submitting this fraction, after trypsic digestion, to nano-LC-MS/MS. In vitro
      experiments with the purified protein showed that it interferes poorly with the
      precipitation of calcium carbonate. Homology searches also could not affiliate
      Upsalin to any other protein of known function, leaving open the question of its
      exact role in shell formation. An antibody raised against an immunogenic peptide
      of Upsalin was found to be specific to this protein and was subsequently assayed
      for immunogold localization of the target protein in the shell, revealing the
      ubiquitous presence of Upsalin in the nacreous and prismatic layers. Recently,
      with the application of high-throughput proteomic studies to shells, the number
      of candidate proteins without clear functions has been increasing exponentially.
      The Upsalin example highlights the crucial need, for the scientific community
      dealing with biomineralization in general, to dedicate the coming years to
      designing experimental approaches, such as gene silencing, that focus on the
      functions of mineral-associated proteins.

PMID- 22474003
TI  - Analyzing repeated measures semi-continuous data, with application to an alcohol
      dependence study.
AB  - Two-part random effects models (Olsen and Schafer,(1) Tooze et al.(2)) have been
      applied to repeated measures of semi-continuous data, characterized by a mixture
      of a substantial proportion of zero values and a skewed distribution of positive
      values. In the original formulation of this model, the natural logarithm of the
      positive values is assumed to follow a normal distribution with a constant
      variance parameter. In this article, we review and consider three extensions of
      this model, allowing the positive values to follow (a) a generalized gamma
      distribution, (b) a log-skew-normal distribution, and (c) a normal distribution
      after the Box-Cox transformation. We allow for the possibility of
      heteroscedasticity. Maximum likelihood estimation is shown to be conveniently
      implemented in SAS Proc NLMIXED. The performance of the methods is compared
      through applications to daily drinking records in a secondary data analysis from
      a randomized controlled trial of topiramate for alcohol dependence treatment. We
      find that all three models provide a significantly better fit than the log-normal
      model, and there exists strong evidence for heteroscedasticity. We also compare
      the three models by the likelihood ratio tests for non-nested hypotheses
      (Vuong(3)). The results suggest that the generalized gamma distribution provides
      the best fit, though no statistically significant differences are found in
      pairwise model comparisons.

PMID- 22474004
TI  - Base-catalyzed direct aldolization of alpha-alkyl-alpha-hydroxy trialkyl
      phosphonoacetates.

PMID- 22474005
TI  - Insight into the rescue of oxidized soluble guanylate cyclase by the activator
      cinaciguat.
AB  - Nitric oxide (NO) signaling mediates many important physiological processes
      through the receptor soluble guanylate cyclase (sGC). Under disease conditions
      sGC heme can be oxidized resulting in NO insensitivity. Here, we show that the
      therapeutic compound cinaciguat (Cin) rescues dysfunctional sGC by direct
      displacement of the oxidized heme.

PMID- 22474006
TI  - NMR-based structure determination of an intertwined coordination cage resembling
      a double trefoil knot.

PMID- 22474007
TI  - Wnt signaling, stem cells, and cancer of the gastrointestinal tract.
AB  - The Wnt signaling pathway was originally uncovered as one of the prototype
      developmental signaling cascades in invertebrates as well as in vertebrates. The
      first indication that Wnt signaling also plays a role in the adult animal came
      from the study of the intestine of Tcf-4 (Tcf7L2) knockout mice. The
      gastrointestinal epithelium continuously self-renews over the lifetime of an
      organism and is, in fact, the most rapidly self-renewing tissue of the mammalian
      body. Recent studies indicate that Wnt signaling plays a central role in the
      biology of gastrointestinal stem cells. Furthermore, mutational activation of the
      Wnt cascade is the principle cause of colon cancer.

PMID- 22474008
TI  - The synchrony and cyclicity of developmental events.
AB  - Many of the morphogenetic processes that occur during development in the mouse
      are based on cyclic events with defined time intervals, as exemplified by
      somitogenesis (every 2 h), hair cycles (every 25 d), and spermatogenesis (every
      35 d). Among these events, somitogenesis is the most dynamic morphogenetic
      mechanism showing clear cyclicity during embryogenesis and is therefore a good
      system with which to review the synchronous and cyclic characteristics of
      developmental pathways. The metameric properties of the somites underpin the
      segmental properties along the anterior-posterior (AP) axis of the body. The
      periodicity of somites is controlled by the so-called segmentation clock
      operating in the presomitic mesoderm (PSM). This tissue contains the somite
      precursor cells that exist only during embryonic development. Both theoretical
      and experimental approaches have contributed to the understanding of the
      mechanism of somite segmentation. This article focuses on how the segmentation
      clock functions to organize the collective behavior of cells and how this
      information is translated into the spatial patterning of segmental somites. The
      interplay between signaling molecules that provides positional information and
      the transcription factors that respond to such positional cues are critical to
      the role of the segmentation clock and are discussed.

PMID- 22474010
TI  - On murine mammary epithelial stem cells: discovery, function, and current status.

PMID- 22474009
TI  - Emerging therapeutics targeting mRNA translation.
AB  - A defining feature of many cancers is deregulated translational control.
      Typically, this occurs at the level of recruitment of the 40S ribosomes to the 5'
      cap of cellular messenger RNAs (mRNAs), the rate-limiting step of protein
      synthesis, which is controlled by the heterotrimeric eukaryotic initiation
      complex eIF4F. Thus, eIF4F in particular, and translation initiation in general,
      represent an exploitable vulnerability and unique opportunity for therapeutic
      intervention in many transformed cells. In this article, we discuss the
      development, mode of action and biological activity of a number of small-molecule
      inhibitors that interrupt PI3K/mTOR signaling control of eIF4F assembly, as well
      as compounds that more directly block eIF4F activity.

PMID- 22474012
TI  - Room-temperature copper-catalyzed oxidation of electron-deficient arenes and
      heteroarenes using air.

PMID- 22474011
TI  - Generation of RNA molecules by a base-catalysed click-like reaction.
AB  - The problem of the abiotic origin of RNA from prebiotically plausible compounds
      remains unsolved. As a potential partial solution, we report the spontaneous
      polymerization of 3',5'-cyclic GMP in water, in formamide, in dimethylformamide,
      and (in water) in the presence of a Bronsted base such as 1,8-diazabicycloundec-7
      ene. The reaction is untemplated, does not require enzymatic activities, is
      thermodynamically favoured and selectively yields 3',5'-bonded ribopolymers
      containing as many as 25 nucleotides. We propose a reaction pathway on the basis
      of 1) the measured stacking of the 3',5'-cyclic monomers, 2) the activation by
      Bronsted bases, 3) the determination (by MALDI-TOF mass spectrometry, by (31)P
      NMR, and by specific ribonucleases) of the molecular species produced. The
      reaction pathway has several of the attributes of a click-like reaction.

PMID- 22474013
TI  - Single-crystal X-ray diffraction, isolated-molecule and cluster electronic
      structure calculations, and scanning electron microscopy in an organic solid:
      models for intramolecular motion in 4,4'-dimethoxybiphenyl.
AB  - This paper brings together field emission scanning electron microscopy, single
      crystal X-ray diffraction, and density functional electronic structure
      calculations in both an isolated molecule and a cluster of seven whole and
      fourteen half molecules of 4,4'-dimethoxybiphenyl to investigate coupled methyl
      group rotation (over a barrier) and methoxy-group libration (meaning a rotation
      from the ground state not all the way to the transition state and back again).
      The structure of the isolated molecule, determined by the electronic structure
      calculations, is compared with the structure of the molecule found in the
      crystal. As the methyl group rotates from its ground state to its transition
      state, the methoxy group rotates 30 degrees  in the isolated molecule and 16
      degrees  in the cluster. The calculated barriers for this coupled methyl-group
      rotation and methoxy group libration in the isolated molecule and in the crystal
      are 12.8 kJ mol(-1) and 10.3 kJ mol(-1) respectively, suggesting that
      intermolecular interactions in the crystal lower the barrier. These barriers are
      compared with the value of 11.5+/-0.5 kJ mol(-1) obtained from solid-state (1)H
      spin-lattice relaxation measurements [P. A. Beckmann and E. Schneider, J. Chem.
      Phys. 2012, 136, 054508.].

PMID- 22474014
TI  - Fluorescence-guided laparoscopic cholecystectomy: a new technique for
      visualization of biliary system by using fluorescein.
AB  - BACKGROUND: Safe cholecystectomy requires confident identification of
      extrahepatic biliary anatomy. This is the first report of the use of fluorescein
      and ultraviolet light to improve visualization of biliary topography during
      laparoscopic cholecystectomy. METHODS: Five patients who had symptomatic
      gallstones underwent laparoscopic cholecystectomy with intraoperative intravenous
      fluorescein injection. Ultraviolet A from an LED light source was used to induce
      fluorescence of bile. It was delivered by a device that was designed and built by
      the authors. RESULTS: Within 4 to 5 minutes the bile ducts were shining with
      green fluorescence and were easily differentiated from the surrounding tissues.
      In all cases, identification of the extrahepatic biliary anatomy by the
      fluorescence technique preceded its identification with conventional white light.
      Fluorescence remained for the whole duration of operation that extended for 42 to
      77 minutes. CONCLUSIONS: At laparoscopic cholecystectomy, intravenous fluorescein
      injection and ultraviolet A excitation induce bile ducts to fluoresce. The
      technique allows better and earlier real-time visualization of biliary anatomy
      than conventional white light. The technique is simple and inexpensive. It serves
      as an additional tool that would improve safety of laparoscopic cholecystectomy.

PMID- 22474015
TI  - Radiofrequency-assisted partial nephrectomy for metanephric adenoma: a case
      report and literature review.
AB  - Metanephric adenoma (MA) is a rare benign tumor, diagnosis of which is often
      carried out after surgical treatment. In case of peripheral lesions, a partial
      nephrectomy (PN)--either open or laparoscopic may be preferred--and, furthermore,
      a radiofrequency (RF)-assisted procedure may facilitate adequate hemostasis. In
      November 2010, the authors performed a RF-assisted PN, according to Habib's
      technique, using a 4-needle bipolar device, on a woman affected by a small
      exophytic MA of the right kidney. Fibrin glue was applied on the cut surface.
      Postoperative course was uneventful, and discharge was on postoperative day 4. MA
      is an extremely rare benign tumor with a favorable prognosis. In case of a
      preoperative cytological diagnosis, a careful follow-up has to be considered. PN
      represents the standard of care for small exophytic MA, and RF-assisted
      procedures allow an excellent hemostasis and a rapid conservative resection, with
      very low morbidity.

PMID- 22474016
TI  - Benefits of post-bariatric surgery for basic plastic surgery practice.

PMID- 22474017
TI  - Single-incision laparoscopic hepatectomy for benign and malignant hepatopathy:
      initial experience in 8 Chinese patients.
AB  - BACKGROUND: The single-incision laparoscopic surgery (SILS) technique has been
      used in many surgical procedures, but there are few reports regarding liver
      surgeries. The purpose of this study was to perform single-incision laparoscopic
      hepatectomy (SILH) using standard laparoscopic instrumentation in 8 Chinese
      patients. The advantages and prospective future applications of SILH are also
      described. METHODS: Selected patients were hospitalized between December 2009 and
      November 2011. The procedure was accomplished through a 2.5-cm transabdominal
      wall incision using a laparoscope and 2 other instruments without the assistance
      of any articulating instruments or single multiport trocar. RESULTS: All
      procedures were successfully performed without the need for supplemental trocars.
      Postoperative pathological examinations were supportive of the preoperative
      diagnoses. No complications such as perioperative hemorrhage or infections
      occurred. CONCLUSION: SILH appears to be a safe approach and the results are
      cosmetically favorable. The accumulation of SILH experience and the development
      of instrumentation are needed for extensive use of this technique in
      hepatectomies.

PMID- 22474018
TI  - Neuropeptide signaling activates dendritic cell-mediated type 1 immune responses
      through neurokinin-2 receptor.
AB  - Neurokinin A (NKA), a neurotransmitter distributed in the central and peripheral
      nervous system, strictly controls vital responses, such as airway contraction, by
      intracellular signaling through neurokinin-2 receptor (NK2R). However, the
      function of NKA-NK2R signaling on involvement in immune responses is less-well
      defined. We demonstrate that NK2R-mediated neuropeptide signaling activates
      dendritic cell (DC)-mediated type 1 immune responses. IFN-gamma stimulation
      significantly induced NK2R mRNA and remarkably enhanced surface protein
      expression levels of bone marrow-derived DCs. In addition, the DC-mediated NKA
      production level was significantly elevated after IFN-gamma stimulation in vivo
      and in vitro. We found that NKA treatment induced type 1 IFN mRNA expressions in
      DCs. Transduction of NK2R into DCs augmented the expression level of surface MHC
      class II and promoted Ag-specific IL-2 production by CD4(+) T cells after NKA
      stimulation. Furthermore, blockade of NK2R by an antagonist significantly
      suppressed IFN-gamma production by both CD4(+) T and CD8(+) T cells stimulated
      with the Ag-loaded DCs. Finally, we confirmed that stimulation with IFN-gamma or
      TLR3 ligand (polyinosinic-polycytidylic acid) significantly induced both NK2R
      mRNA and surface protein expression of human PBMC-derived DCs, as well as
      enhanced human TAC1 mRNA, which encodes NKA and Substance P. Thus, these findings
      indicate that NK2R-dependent neuropeptide signaling regulates Ag-specific T cell
      responses via activation of DC function, suggesting that the NKA-NK2R cascade
      would be a promising target in chronic inflammation caused by excessive type 1
      dominant immunity.

PMID- 22474019
TI  - NIK prevents the development of hypereosinophilic syndrome-like disease in mice
      independent of IKKalpha activation.
AB  - Immune cell-mediated tissue injury is a common feature of different inflammatory
      diseases, yet the pathogenetic mechanisms and cell types involved vary
      significantly. Hypereosinophilic syndrome (HES) represents a group of
      inflammatory diseases that is characterized by increased numbers of pathogenic
      eosinophilic granulocytes in the peripheral blood and diverse organs. On the
      basis of clinical and laboratory findings, various forms of HES have been
      defined, yet the molecular mechanism and potential signaling pathways that drive
      eosinophil expansion remain largely unknown. In this study, we show that mice
      deficient of the serine/threonine-specific protein kinase NF-kappaB-inducing
      kinase (NIK) develop a HES-like disease, reflected by progressive blood and
      tissue eosinophilia, tissue injury, and premature death at around 25-30 wk of
      age. Similar to the lymphocytic form of HES, CD4(+) T cells from NIK-deficient
      mice express increased levels of Th2-associated cytokines, and eosinophilia and
      survival of NIK-deficient mice could be prevented completely by genetic ablation
      of CD4(+) T cells. Experiments based on bone marrow chimeric mice, however,
      demonstrated that inflammation in NIK-deficient mice depended on radiation
      resistant tissues, implicating that NIK-deficient immune cells mediate
      inflammation in a nonautonomous manner. Surprisingly, disease development was
      independent of NIK's known function as an IkappaB kinase alpha (IKKalpha) kinase,
      because mice carrying a mutation in the activation loop of IKKalpha, which is
      phosphorylated by NIK, did not develop inflammatory disease. Our data show that
      NIK activity in nonhematopoietic cells controls Th2 cell development and prevents
      eosinophil-driven inflammatory disease, most likely using a signaling pathway
      that operates independent of the known NIK substrate IKKalpha.

PMID- 22474020
TI  - IL-2 simultaneously expands Foxp3+ T regulatory and T effector cells and confers
      resistance to severe tuberculosis (TB): implicative Treg-T effector cooperation
      in immunity to TB.
AB  - The possibility that simultaneous expansion of T regulatory cells (Treg) and T
      effector cells early postinfection can confer some immunological benefits has not
      been studied. In this study, we tested the hypothesis that early, simultaneous
      cytokine expansion of Treg and T effector cells in a tissue infection site can
      allow these T cell populations to act in concert to control tissue
      inflammation/damage while containing infection. IL-2 treatments early after
      Mycobacterium tuberculosis infection of macaques induced simultaneous expansion
      of CD4(+)CD25(+)Foxp3(+) Treg, CD8(+)CD25(+)Foxp3(+) T cells, and CD4(+) T
      effector/CD8(+) T effector/Vgamma2Vdelta2 T effector populations producing anti
      M. tuberculosis cytokines IFN-gamma and perforin, and conferred resistance to
      severe TB inflammation and lesions. IL-2-expanded Foxp3(+) Treg readily
      accumulated in pulmonary compartment, but despite this, rapid pulmonary
      trafficking/accumulation of IL-2-activated T effector populations still occurred.
      Such simultaneous recruitments of IL-2-expanded Treg and T effector populations
      to pulmonary compartment during M. tuberculosis infection correlated with IL-2
      induced resistance to TB lesions without causing Treg-associated increases in M.
      tuberculosis burdens. In vivo depletion of IL-2-expanded CD4(+)Foxp3(+) Treg and
      CD4(+) T effectors during IL-2 treatment of M. tuberculosis-infected macaques
      significantly reduced IL-2-induced resistance to TB lesions, suggesting that IL-2
      expanded CD4(+) T effector cells and Treg contributed to anti-TB immunity. Thus,
      IL-2 can simultaneously activate and expand T effector cells and Foxp3(+) Treg
      populations and confer resistance to severe TB without enhancing M. tuberculosis
      infection.

PMID- 22474021
TI  - High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C
      restricted CTL selective pressure associated with an AIDS-protective
      polymorphism.
AB  - Delayed HIV-1 disease progression is associated with a single nucleotide
      polymorphism upstream of the HLA-C gene that correlates with differential
      expression of the HLA-C Ag. This polymorphism was recently shown to be a marker
      for a protective variant in the 3'UTR of HLA-C that disrupts a microRNA binding
      site, resulting in enhanced HLA-C expression at the cell surface. Whether
      individuals with "high" HLA-C expression show a stronger HLA-C-restricted immune
      response exerting better viral control than that of their counterparts has not
      been established. We hypothesized that the magnitude of the HLA-C-restricted
      immune pressure on HIV would be greater in subjects with highly expressed HLA-C
      alleles. Using a cohort derived from a unique narrow source epidemic in China, we
      identified mutations in HIV proviral DNA exclusively associated with HLA-C, which
      were used as markers for the intensity of the immune pressure exerted on the
      virus. We found an increased frequency of mutations in individuals with highly
      expressed HLA-C alleles, which also correlated with IFN-gamma production by HLA-C
      restricted CD8(+) T cells. These findings show that immune pressure on HIV is
      stronger in subjects with the protective genotype and highlight the potential
      role of HLA-C-restricted responses in HIV control. This is, to our knowledge, the
      first in vivo evidence supporting the protective role of HLA-C-restricted
      responses in nonwhites during HIV infection.

PMID- 22474024
TI  - Functional changes in myeloid-derived suppressor cells (MDSCs) during tumor
      growth: FKBP51 contributes to the regulation of the immunosuppressive function of
      MDSCs.
AB  - Myeloid-derived suppressor cells (MDSCs) are increased by tumor-derived factors
      and suppress anti-tumor immunity. MDSCs obtained at a late time point after tumor
      injection had stronger suppressive activity than MDSCs obtained at an early time
      point, as measured by T cell proliferation assays. To find factors in MDSCs that
      change during tumor growth, we analyzed gene expression profiles from MDSCs at
      different time points after tumor injection. We found that immune response
      related genes were downregulated but protumor function-related genes were
      upregulated in both monocytic MDSCs (Mo-MDSCs) and polymorphonuclear granulocytic
      MDSCs (PMN-MDSCs) at the late time point. Among differentially expressed genes,
      FK506 binding protein 51 (FKBP51), which is a member of the immunophilin protein
      family and plays a role in immunoregulation, was increased in the Mo-MDSCs and
      PMN-MDSCs isolated from the late time points. Experiments using small interfering
      RNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the
      regulation of the suppressive function of MDSCs by increasing inducible NO
      synthase, arginase-1, and reactive oxygen species levels and enhancing NF-kappaB
      activity. Collectively, our data suggest that FKBP51 is a novel molecule that can
      be targeted to regulate the immunosuppressive function of MDSCs.

PMID- 22474022
TI  - Pulmonary inflammation induced by subacute ozone is augmented in adiponectin
      deficient mice: role of IL-17A.
AB  - Pulmonary responses to ozone, a common air pollutant, are augmented in obese
      individuals. Adiponectin, an adipose-derived hormone that declines in obesity,
      has regulatory effects on the immune system. To determine the role of adiponectin
      in the pulmonary inflammation induced by extended (48-72 h) low-dose (0.3 parts
      per million) exposure to ozone, adiponectin-deficient (Adipo(-/-)) and wild-type
      mice were exposed to ozone or to room air. In wild-type mice, ozone exposure
      increased total bronchoalveolar lavage (BAL) adiponectin. Ozone-induced lung
      inflammation, including increases in BAL neutrophils, protein (an index of lung
      injury), IL-6, keratinocyte-derived chemokine, LPS-induced CXC chemokine, and G
      CSF were augmented in Adipo(-/-) versus wild-type mice. Ozone also increased IL
      17A mRNA expression to a greater extent in Adipo(-/-) versus wild-type mice.
      Moreover, compared with control Ab, anti-IL-17A Ab attenuated ozone-induced
      increases in BAL neutrophils and G-CSF in Adipo(-/-) but not in wild-type mice,
      suggesting that IL-17A, by promoting G-CSF release, contributed to augmented
      neutrophilia in Adipo(-/-) mice. Flow cytometric analysis of lung cells revealed
      that the number of CD45(+)/F4/80(+)/IL-17A(+) macrophages and gammadelta T cells
      expressing IL-17A increased after ozone exposure in wild-type mice and further
      increased in Adipo(-/-) mice. The IL-17(+) macrophages were CD11c(-)
      (interstitial macrophages), whereas CD11c(+) macrophages (alveolar macrophages)
      did not express IL-17A. Taken together, the data are consistent with the
      hypothesis that adiponectin protects against neutrophil recruitment induced by
      extended low-dose ozone exposure by inhibiting the induction and/or recruitment
      of IL-17A in interstitial macrophages and/or gammadelta T cells.

PMID- 22474023
TI  - The Asp299Gly polymorphism alters TLR4 signaling by interfering with recruitment
      of MyD88 and TRIF.
AB  - Asp(299)Gly (D299G) and, to a lesser extent, Thr(399)Ile (T399I) TLR4
      polymorphisms have been associated with gram-negative sepsis and other infectious
      diseases, but the mechanisms by which they affect TLR4 signaling are unclear. In
      this study, we determined the impact of the D299G and T399I polymorphisms on TLR4
      expression, interactions with myeloid differentiation factor 2 (MD2), LPS
      binding, and LPS-mediated activation of the MyD88- and Toll/IL-1R resistance
      domain-containing adapter inducing IFN-beta (TRIF) signaling pathways.
      Complementation of human embryonic kidney 293/CD14/MD2 transfectants with wild
      type (WT) or mutant yellow fluorescent protein-tagged TLR4 variants revealed
      comparable total TLR4 expression, TLR4-MD2 interactions, and LPS binding. FACS
      analyses with anti-TLR4 Ab showed only minimal changes in the cell-surface levels
      of the D299G TLR4. Cells transfected with D299G TLR4 exhibited impaired LPS
      induced phosphorylation of p38 and TANK-binding kinase 1, activation of NF-kappaB
      and IFN regulatory factor 3, and induction of IL-8 and IFN-beta mRNA, whereas
      T399I TLR4 did not cause statistically significant inhibition. In contrast to WT
      TLR4, expression of the D299G mutants in TLR4(-/-) mouse macrophages failed to
      elicit LPS-mediated induction of TNF-alpha and IFN-beta mRNA.
      Coimmunoprecipitation revealed diminished LPS-driven interaction of MyD88 and
      TRIF with the D299G TLR4 species, in contrast to robust adapter recruitment
      exhibited by WT TLR4. Thus, the D299G polymorphism compromises recruitment of
      MyD88 and TRIF to TLR4 without affecting TLR4 expression, TLR4-MD2 interaction,
      or LPS binding, suggesting that it interferes with TLR4 dimerization and assembly
      of intracellular docking platforms for adapter recruitment.

PMID- 22474025
TI  - Surfactant protein A modulates induction of regulatory T cells via TGF-beta.
AB  - TCR signaling plays a critical role in regulatory T cell (Treg) development.
      However, the mechanism for tissue-specific induction of Tregs in the periphery
      remains unclear. We observed that surfactant protein A (SP-A)-deficient mice have
      impaired expression of Foxp3 and fewer CD25(+)Foxp3(+) Tregs after ex vivo
      stimulation and after stimulation with LPS in vivo. The addition of exogenous SP
      A completely reversed this phenotype. Although SP-A is known to inhibit T cell
      proliferation under certain activation conditions, both IL-2 levels as well as
      active TGF-beta levels increase on extended culture with exogenous SP-A,
      providing a key mechanism for the maintenance and induction of Tregs. In
      addition, kinetic suppression assays demonstrate that SP-A enhances the frequency
      of functional Foxp3(+) Tregs in responder T cell populations in a TGF-beta
      dependent manner. In mice treated with LPS in vivo, Tregs increased ~160% in wild
      type mice compared with only a 50% increase in LPS-treated SP-A(-/-) mice 8 d
      after exposure. Taken together, these findings support the hypothesis that SP-A
      affects T cell immune function by the induction of Tregs during activation.

PMID- 22474026
TI  - Children with islet autoimmunity and enterovirus infection demonstrate a distinct
      cytokine profile.
AB  - Cytokines are upregulated in prediabetes, but their relationship with Enterovirus
      (EV) infection and development of islet autoimmunity is unknown. Cytokines (n =
      65) were measured using Luminex xMAP technology in a nested case-control study of
      67 children with a first-degree relative with type 1 diabetes: 27 with islet
      autoantibodies (Ab(+)) and 40 age-matched persistently autoantibody negative (Ab(
      )) control subjects. Of 74 samples, 37 (50%) were EV-PCR(+) in plasma and/or
      stool (EV(+)) and the remainder were negative for EV and other viruses (EV(-)).
      Fifteen cytokines, chemokines, and growth factors were elevated (P <= 0.01) in
      Ab(+) versus Ab(-) children (interleukin [IL]-1beta, IL-5, IL-7, IL-12(p70), IL
      16, IL-17, IL-20, IL-21, IL-28A, tumor necrosis factor-alpha, chemokine C-C motif
      ligand [CCL]13, CCL26, chemokine C-X-C motif ligand 5, granulocyte-macrophage
      colony-stimulating factor, and thrombopoietin); most have proinflammatory
      effects. In EV(+) versus EV(-) children, IL-10 was higher (P = 0.005), while IL
      21 was lower (P = 0.008). Cytokine levels did not differ between Ab(+)EV(+) and
      Ab(+)EV(-) children. Heat maps demonstrated clustering of some proinflammatory
      cytokines in Ab(+) children, suggesting they are coordinately regulated. In
      conclusion, children with islet autoimmunity demonstrate higher levels of
      multiple cytokines, consistent with an active inflammatory process in the
      prediabetic state, which is unrelated to coincident EV infection. Apart from
      differences in IL-10 and IL-21, EV infection was not associated with a specific
      cytokine profile.

PMID- 22474027
TI  - CCR5 plays a critical role in obesity-induced adipose tissue inflammation and
      insulin resistance by regulating both macrophage recruitment and M1/M2 status.
AB  - C-C motif chemokine receptor (CCR)2 and its ligand, monocyte chemoattractant
      protein (MCP)-1, are pivotal for adipose tissue macrophage (ATM) recruitment and
      the development of insulin resistance. However, other chemokine systems also may
      play a role in these processes. In this study, we investigated the role of CCR5
      in obesity-induced adipose tissue inflammation and insulin resistance. We
      analyzed expression levels of CCR5 and its ligands in white adipose tissue (WAT)
      of genetically (ob/ob) and high-fat (HF) diet-induced obese (DIO) mice.
      Furthermore, we examined the metabolic phenotype of Ccr5(-/-) mice. CCR5 and its
      ligands were markedly upregulated in WAT of DIO and ob/ob mice. Fluorescence
      activated cell sorter analysis also revealed that DIO mice had a robust increase
      in CCR5(+) cells within ATMs compared with chow-fed mice. Furthermore, Ccr5(-/-)
      mice were protected from insulin resistance, glucose intolerance, and hepatic
      steatosis induced by HF feeding. The effects of loss of CCR5 were related to both
      reduction of total ATM content and an M2-dominant shift in ATM polarization. It
      is noteworthy that transplantation of Ccr5(-/-) bone marrow was sufficient to
      protect against impaired glucose tolerance. CCR5 plays a critical role in ATM
      recruitment and polarization and subsequent development of insulin resistance.

PMID- 22474028
TI  - Skeletal muscle protein tyrosine phosphatase 1B regulates insulin sensitivity in
      African Americans.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is postulated to modulate insulin action
      by dephosphorylating the insulin receptor signaling proteins and attenuating
      insulin signaling. We sought to determine the relationship of skeletal muscle
      PTP1B to whole-body insulin sensitivity. We studied 17 African Americans with
      type 2 diabetes mellitus (T2DM) and 16 without diabetes. PTP1B gene expression
      and protein abundance were determined in the biopsied skeletal muscles at the
      baseline of a hyperinsulinemic-euglycemic clamp. PTP1B gene expression was
      significantly higher in subjects with T2DM versus control (P < 0.0001) and
      remained significantly different after adjusting for age and insulin sensitivity
      (P = 0.05). PTP1B gene expression was positively related to protein abundance
      (r(s) = 0.39; P = 0.03; adjusted for age and insulin sensitivity) and negatively
      related to insulin sensitivity (r(s) = -0.52; P = 0.002; adjusted for age).
      Overexpression and interference RNA of PTP1B were performed in primary human
      skeletal muscle culture. PTP1B overexpression resulted in reduction of Akt
      phosphorylation in the control subjects. Moreover, interference RNA transfection
      downregulated PTP1B expression and enhanced Akt phosphorylation in subjects with
      T2DM. These data show that skeletal muscle PTP1B gene expression is increased in
      African American subjects with T2DM, is negatively associated with whole-body
      insulin sensitivity, and contributes to modulation of insulin signaling.

PMID- 22474030
TI  - Involvement of intracellular glutathione in regulating isoline-induced
      cytotoxicity in human normal liver L-02 cells.
AB  - Pyrrolizidine alkaloid isoline is isolated from the traditional Chinese medicine
      Ligularia duciformis. Our previous reports have already demonstrated isoline
      induced liver injury in mice. The present study is designed to observe the
      involvement of intracellular reduced glutathione (GSH) in isoline-induced
      cytotoxicity in human normal liver L-02 cells. The results showed that isoline
      decreased the cellular GSH and the ratio of GSH and oxidized glutathione in a
      time- and concentration-dependent manner in L-02 cells. l-Buthionine-S-R
      sulfoximine (BSO) is reported to inhibit cellular GSH biosynthesis, and further
      results showed that isoline decreased the cell viability in L-02 cells after
      pretreated with 25 MUM BSO for 24 h. Furthermore, adducts of isoline and GSH were
      identified in L-02 cells using liquid chromatography/electrospray ionization
      tandem mass spectrometry (ion trap) for the first time. In conclusion, our study
      provides the strongest evidence to support the important roles of GSH in
      regulating isoline-induced cytotoxicity in human normal liver L-02 cells. 

PMID- 22474029
TI  - Consistent directions of effect for established type 2 diabetes risk variants
      across populations: the population architecture using Genomics and Epidemiology
      (PAGE) Consortium.
AB  - Common genetic risk variants for type 2 diabetes (T2D) have primarily been
      identified in populations of European and Asian ancestry. We tested whether the
      direction of association with 20 T2D risk variants generalizes across six major
      racial/ethnic groups in the U.S. as part of the Population Architecture using
      Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control
      subjects of European American, African American, Hispanic, East Asian, American
      Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio
      [OR] >1 for putative risk allele) associations ranged from 69% in American
      Indians to 100% in European Americans. Of the nine variants where we observed
      significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) <
      0.05), eight were positively associated with risk (OR >1) in at least five
      groups. The marked directional consistency of association observed for most
      genetic variants across populations implies a shared functional common variant in
      each region. Fine-mapping of all loci will be required to reveal markers of risk
      that are important within and across populations.

PMID- 22474031
TI  - Evaluation of extracting titanium dioxide from water-based paint sludge in auto
      manufacturing industries and its application in paint production.
AB  - Almost 2555-4380 tons of paint sludge are produced annually in an auto
      manufacturing plant; recycling and reproduction of beneficial materials such as
      titanium dioxide (TiO2) and its application in paint production from paint sludge
      are evaluated in this article. The disposal of these sludge is environmentally
      important and is the main and most serious challenge for auto-manufacturing
      units. Today, these sludge are recognized as toxic wastes, whose disposal is much
      costly and constrained by environmental standards. Controlled disposal requires
      spaces, which are expensive and impermeable, because the sludge contains large
      amounts of hazardous materials such as heavy metals, solvents, and other
      materials polluting wells, springs, and other water resources. In this research,
      X-ray diffraction spectroscopy was carried out to determine the types of sludge
      combinations. Then, chemical digestion and centrifuge was used to extract TiO2,
      the extracted TiO2 reached 67.41% using these techniques. Next, a powder
      containing TiO2 in a certain percentage was used for paint production. Here, not
      only the amount of sludge decreased to as much as 70% but also the fresh paint
      required annually will be reduced by 21%. Furthermore, all heavy metals and toxic
      wastes will be removed as an environmental challenge. 

PMID- 22474032
TI  - Influenza vaccination or treatment for influenza-associated myocardial
      infarction.

PMID- 22474033
TI  - Staphylococcus aureus manganese transport protein C is a highly conserved cell
      surface protein that elicits protective immunity against S. aureus and
      Staphylococcus epidermidis.
AB  - Staphylococcus aureus and other staphylococci cause severe human disease, and
      there are currently no vaccines available. We evaluated whether manganese
      transport protein C (MntC), which is conserved across the staphylococcal species
      group, could confer protection against S. aureus and Staphylococcus epidermidis.
      In vivo analysis of S. aureus MntC expression revealed that expression occurs
      very early during the infectious cycle. Active immunization with MntC was
      effective at reducing the bacterial load associated with S. aureus and S.
      epidermidis infection in an acute murine bacteremia model. Anti-MntC monoclonal
      antibodies have been identified that can bind S. aureus and S. epidermidis cells
      and are protective in an infant rat passive protection model and induce
      neutrophil respiratory burst activity. This is the first description of a protein
      that has the potential to provide protection across the staphylococcal species
      group.

PMID- 22474034
TI  - C-reactive protein and the Framingham coronary risk score in patients newly
      diagnosed with intermittent claudication: a prospective study.
AB  - OBJECTIVE: To investigate the relationship between serum C-reactive protein (CRP)
      levels and the calculated 10-year Framingham risk score (FRS) in patients newly
      diagnosed with intermittent claudication. METHODS: Serum CRP levels were measured
      in 90 patients newly diagnosed with intermittent claudication over a 12-month
      period. In all, 76 patients (53 males [70%], mean age 63.3 +/- 9.3) were included
      in the analysis. RESULTS: Log-transformed CRP levels significantly correlated
      with total FRS (r = .34, P = .002). Participants were divided into 4 groups
      according to log-CRP levels. Analysis of variance showed a statistically
      significant difference between the 4 groups in terms of mean FRS, P = .003. Post
      hoc comparisons indicated that group 1 was significantly different from group 4,
      P = .002. Analysis of covariance showed a significant difference between the 4
      groups of log-CRP levels in terms of mean FRS, P = .008. CONCLUSION: There is an
      increased 10-year risk of coronary heart disease associated with increased plasma
      concentration of CRP in patients newly diagnosed with intermittent claudication.

PMID- 22474035
TI  - ADAM10 mediates vascular injury induced by Staphylococcus aureus alpha-hemolysin.
AB  - Staphylococcus aureus is a leading cause of bacteremia and sepsis. The
      interaction of S. aureus with the endothelium is central to bloodstream infection
      pathophysiology yet remains ill-understood. We show herein that staphylococcal
      alpha-hemolysin, a pore-forming cytotoxin, is required for full virulence in a
      murine sepsis model. The alpha-hemolysin binding to its receptor A-disintegrin
      and metalloprotease 10 (ADAM10) upregulates the receptor's metalloprotease
      activity on endothelial cells, causing vascular endothelial-cadherin cleavage and
      concomitant loss of endothelial barrier function. These cellular injuries and
      sepsis severity can be mitigated by ADAM10 inhibition. This study therefore
      provides mechanistic insight into toxin-mediated endothelial injury and suggests
      new therapeutic approaches for staphylococcal sepsis.

PMID- 22474036
TI  - Transmission of human herpesvirus type 8 infection within families in american
      indigenous populations from the Brazilian Amazon.
AB  - BACKGROUND: The intrafamilial dynamics of endemic infection with human
      herpesvirus type 8 (HHV-8) in Amerindian populations is unknown. METHODS: Serum
      samples were obtained from 517 Amerindians and tested for HHV-8 anti-latent
      nuclear antigen (anti-LANA) and antilytic antibodies by immunofluorescence
      assays. Logistic regression and mixed logistic models were used to estimate the
      odds of being HHV-8 seropositive among intrafamilial pairs. RESULTS: HHV-8
      seroprevalence by either assay was 75.4% (95% confidence interval [CI]: 71.5%
      79.1%), and it was age-dependent (P(trend) < .001). Familial dependence in HHV-8
      seroprevalence by either assay was found between mother-offspring (odds ratio
      [OR], 5.44; 95% CI: 1.62-18.28) and siblings aged >=10 years (OR 4.42, 95% CI:
      1.70-11.45) or siblings in close age range (<5 years difference) (OR 3.37, 95%
      CI: 1.21-9.40), or in families with large (>4) number of siblings (OR, 3.20, 95%
      CI: 1.33-7.67). In separate analyses by serological assay, there was strong
      dependence in mother-offspring (OR 8.94, 95% CI: 2.94-27.23) and sibling pairs
      aged >=10 years (OR, 11.91, 95% CI: 2.23-63.64) measured by LANA but not lytic
      antibodies. CONCLUSIONS: This pattern of familial dependence suggests that, in
      this endemic population, HHV-8 transmission mainly occurs from mother to
      offspring and between close siblings during early childhood, probably via saliva.
      The mother to offspring dependence was derived chiefly from anti-LANA antibodies.

PMID- 22474037
TI  - Risk of tuberculosis reactivation with tofacitinib (CP-690550).
AB  - Individuals with latent tuberculosis infection (LTBI) live with a risk of
      reactivation, and several treatments for chronic inflammatory conditions are
      highly associated with such reactivation. A new Janus kinase inhibitor,
      tofacitinib (CP-690550), has shown promising results for treatment of
      inflammatory disorders, thus raising concerns of risk of active tuberculosis. Our
      goal was to characterize the impact of tofacitinib on LTBI using a mouse model of
      contained tuberculosis. Our data indicate that tofacitinib reduces host
      containment of Mycobacterium tuberculosis and promotes bacterial replication in
      the lungs, suggesting tuberculosis reactivation. Tofacitinib may carry a
      significant risk for LTBI reactivation in humans.

PMID- 22474038
TI  - Induction of indoleamine 2,3-dioxygenase by uropathogenic bacteria attenuates
      innate responses to epithelial infection.
AB  - Uropathogenic Escherichia coli (UPEC) are the chief cause of urinary tract
      infections. Although neutrophilic inflammation is a hallmark of disease, previous
      data indicate that UPEC promotes local dampening of host innate immune responses.
      Here, we show that UPEC attenuates innate responses to epithelial infection by
      inducing expression of indoleamine 2,3-dioxygenase (IDO), a host enzyme with
      previously defined roles in adaptive immune regulation. UPEC induced IDO
      expression in human uroepithelial cells and polymorphonuclear leukocytes (PMN) in
      vitro and in bladder tissue during murine cystitis via a noncanonical, interferon
      independent pathway. In the bladders of UPEC-infected IDO-deficient mice, we
      observed augmented expression of proinflammatory cytokines and local
      inflammation, correlated with reduced survival of extracellular bacteria.
      Pharmacologic inhibition of IDO also increased human PMN transepithelial
      migration. Stimulation of IDO expression therefore represents a pathogen strategy
      to create local immune privilege at epithelial surfaces, attenuating innate
      responses to promote colonization and the establishment of infection.

PMID- 22474039
TI  - Multiorgan insulin sensitivity in lean and obese subjects.
AB  - OBJECTIVE: To provide a comprehensive assessment of multiorgan insulin
      sensitivity in lean and obese subjects with normal glucose tolerance. RESEARCH
      DESIGN AND METHODS: The hyperinsulinemic-euglycemic clamp procedure with stable
      isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 +/- 0.6
      kg/m(2), mean +/- SEM) and 26 lean (22.5 +/- 0.3 kg/m(2)) subjects with normal
      glucose tolerance. Insulin was infused at different rates to achieve low, medium,
      and high physiological plasma concentrations. RESULTS: In obese subjects,
      palmitate and glucose R(a) in plasma decreased with increasing plasma insulin
      concentrations. The decrease in endogenous glucose R(a) was greater during low-,
      medium-, and high-dose insulin infusions (69 +/- 2, 74 +/- 2, and 90 +/- 2%) than
      the suppression of palmitate R(a) (52 +/- 4, 68 +/- 1, and 79 +/- 1%). Insulin
      mediated increase in glucose disposal ranged from 24 +/- 5% at low to 253 +/- 19%
      at high physiological insulin concentrations. The suppression of palmitate R(a)
      and glucose R(a) were greater in lean than obese subjects during low-dose insulin
      infusion but were the same in both groups during high-dose insulin infusion,
      whereas stimulation of glucose R(d) was greater in lean than obese subjects
      across the entire physiological range of plasma insulin. CONCLUSIONS: Endogenous
      glucose production and adipose tissue lipolytic rate are both very sensitive to
      small increases in circulating insulin, whereas stimulation of muscle glucose
      uptake is minimal until high physiological plasma insulin concentrations are
      reached. Hyperinsulinemia within the normal physiological range can compensate
      for both liver and adipose tissue insulin resistance, but not skeletal muscle
      insulin resistance, in obese people who have normal glucose tolerance.

PMID- 22474040
TI  - Changes in treatment adherence and glycemic control during the transition to
      adolescence in type 1 diabetes.
AB  - OBJECTIVE: To test models of unidirectional and bidirectional change between
      treatment adherence and glycemic control in youth with type 1 diabetes. RESEARCH
      DESIGN AND METHODS: We conducted a 2-year longitudinal, multisite study of 225
      youth with type 1 diabetes recruited at the cusp of adolescence (aged 9-11 years)
      to describe the mutual influences of glycemic control as measured by HbA(1c) and
      treatment adherence as measured by blood glucose monitoring frequency (BGMF)
      during the transition to adolescence. RESULTS: HbA(1c) increased from 8.2 to 8.6%
      (P < 0.001) and BGMF decreased from 4.9 to 4.5 checks per day (P < 0.02) during
      the 2-year period. Changes in the BGMF slope predicted changes in HbA(1c). A
      change (increase) in HbA(1c) was associated with a change (decrease) in BGMF of
      1.26 (P < 0.001) after controlling for covariates. CONCLUSIONS: The magnitude of
      the effect of declining treatment adherence (BGMF) on glycemic control in young
      adolescents may be even greater than declines observed among older adolescents.
      BGMF offers a powerful tool for targeted management of glycemic control for type
      1 diabetes during the critical transition to adolescence.

PMID- 22474041
TI  - Association of high pulse pressure with proteinuria in subjects with diabetes,
      prediabetes, or normal glucose tolerance in a large Japanese general population
      sample.
AB  - OBJECTIVE: To examine whether there is a difference in the association between
      high pulse pressure and proteinuria, independent of other blood pressure (BP)
      indices, such as systolic or diastolic BP, among subjects with diabetes,
      prediabetes, or normal glucose tolerance. RESEARCH DESIGN AND METHODS: Using a
      nationwide health checkup database of 228,778 Japanese aged >= 20 years (mean
      63.2 years; 39.3% men; none had pre-existing cardiovascular disease), we examined
      the association between high pulse pressure, defined as the highest quintile of
      pulse pressure (>= 63 mmHg, n = 40,511), and proteinuria (>= 1+ on dipstick, n =
      12,090) separately in subjects with diabetes (n = 27,913), prediabetes (n =
      100,214), and normal glucose tolerance (n = 100,651). RESULTS: The prevalence of
      proteinuria was different among subjects with diabetes, prediabetes, and normal
      glucose tolerance (11.3 vs. 5.0 vs. 3.9%, respectively; P < 0.001). In subjects
      with diabetes, but not those with prediabetes or normal glucose tolerance, high
      pulse pressure was associated with proteinuria independently of significant
      covariates, including systolic BP (odds ratio 1.15 [95% CI 1.04-1.28]) or
      diastolic or mean BP (all P < 0.01). In patients with diabetes, a +1 SD increase
      of pulse pressure (+13 mmHg) was associated with proteinuria, even after
      adjustment for systolic BP (1.07 [1.00-1.13]) or diastolic or mean BP (all P <
      0.05). CONCLUSIONS: Among the Japanese general population, there was a
      significant difference in the association between high pulse pressure and
      proteinuria among subjects with diabetes, prediabetes, and normal glucose
      tolerance. Only in diabetes was high pulse pressure associated with proteinuria
      independent of systolic, diastolic, or mean BP levels.

PMID- 22474042
TI  - A prospective study of the association between quantity and variety of fruit and
      vegetable intake and incident type 2 diabetes.
AB  - OBJECTIVE: The association between quantity of fruit and vegetable (F&V) intake
      and risk of type 2 diabetes (T2D) is not clear, and the relationship with variety
      of intake is unknown. The current study examined the association of both quantity
      and variety of F&V intake and risk of T2D. RESEARCH DESIGN AND METHODS: We
      examined the 11-year incidence of T2D in relation to quantity and variety of
      fruit, vegetables, and combined F&V intake in a case-cohort study of 3,704
      participants (n = 653 diabetes cases) nested within the European Prospective
      Investigation into Cancer and Nutrition-Norfolk study, who completed 7-day
      prospective food diaries. Variety of intake was derived from the total number of
      different items consumed in a 1-week period. Multivariable, Prentice-weighted Cox
      regression was used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A
      greater quantity of combined F&V intake was associated with 21% lower hazard of
      T2D (HR 0.79 [95% CI 0.62-1.00]) comparing extreme tertiles, in adjusted analyses
      including variety. Separately, quantity of vegetable intake (0.76 [0.60-0.97]),
      but not fruit, was inversely associated with T2D in adjusted analysis. Greater
      variety in fruit (0.70 [0.53-0.91]), vegetable (0.77 [0.61-0.98]), and combined
      F&V (0.61 [0.48-0.78]) intake was associated with a lower hazard of T2D,
      independent of known confounders and quantity of intake comparing extreme
      tertiles. CONCLUSIONS: These findings suggest that a diet characterized by a
      greater quantity of vegetables and a greater variety of both F&V intake is
      associated with a reduced risk of T2D.

PMID- 22474043
TI  - Adverse reactions following administration of an ionic iodinated contrast media
      in anesthetized dogs.
AB  - This retrospective study was conducted to identify hemodynamic alterations
      associated with the administration of an ionic iodinated contrast media in dogs.
      Case records of 49 dogs that were anesthetized for computed tomography scanning
      were reviewed. Values for heart rate (HR) and direct arterial pressure were
      obtained. Overall, 37% of dogs had a >=20% change in either HR or systolic
      arterial pressure from baseline values. Four dogs (8%) became tachycardic and two
      dogs (4%) became bradycardic. Eight dogs (16%) became hypertensive and two dogs
      (4%) became hypotensive. A significant proportion of dogs experienced changes in
      HR and blood pressure following IV administration of an ionic iodinated contrast
      media under general anesthesia.

PMID- 22474044
TI  - Iatrogenic hyperadrenocorticism, calcinosis cutis, and myocardial infarction in a
      dog treated for IMT.
AB  - An 8 yr old male English bulldog receiving treatment for immune-mediated
      thrombocytopenia was diagnosed with calcinosis cutis 90 days after initiation of
      corticosteroid therapy. Twenty-four days later, the patient presented in a
      comatose state after collapsing and was euthanized. Postmortem examination
      revealed coronary arteriosclerosis and myocardial infarction leading to
      congestive heart failure. Calcinosis cutis and myocardial necrosis were most
      likely complications associated with administration of corticosteroids in this
      dog. Important implications regarding the classification of calcinosis cutis and
      the use of immunosuppressive doses of corticosteroids are discussed.

PMID- 22474045
TI  - Radiographic characterization of enlarged sternal lymph nodes in 71 dogs and 13
      cats.
AB  - In this retrospective study, radiographically enlarged sternal lymph nodes (LNs)
      were evaluated in 71 dogs and 13 cats for average size, location, and most
      representative radiographic view. Concurrent clinical diagnoses were also noted
      and grouped into one of three following categories: neoplastic, inflammatory, or
      hematologic. There were no statistically significant differences in LN size
      between lateral views within each species. Enlarged sternal LNs were more
      cranially positioned in dogs than cats. No statistical difference was noted
      between right and left laterals, as to on which projection the enlarged sterna
      lymph nodes was seen best. Neoplastic disease (78.9%) was the most prevalent
      condition seen in association with LN enlargement in dogs, followed by primary
      infectious or inflammatory diseases (14.1%) and various hematologic conditions
      (7.0%). In cats, neoplasia was also most common (69.2%), followed by inflammatory
      diseases (30.8%). No hematologic conditions were noted in cats. The most common
      etiologic agent seen concurrently with enlarged sternal LNs in both dogs (33.8%)
      and cats (38.5%) was malignant lymphoma. The results of this study provide a
      clinically useful representation of the average size and location of
      radiographically enlarged sternal LNs for dogs and cats. The diseases represented
      demonstrate the wide spectrum of potential causes of sternal lymphadenopathy.

PMID- 22474046
TI  - Feline histoplasmosis: a retrospective study of 22 cases (1986-2009).
AB  - Twenty-two cases of feline histoplasmosis seen at the Virginia-Maryland Regional
      College of Veterinary Medicine Teaching Hospital between 1986 and 2009 were
      reviewed. The median age of affected cats was 9 yr (mean, 8.8 yr). Female
      domestic shorthairs were more commonly affected. The clinical presentation of
      most cases was nonspecific. The most common presenting complaints included
      weakness, lymphadenopathy, weight loss, and anorexia. Less frequent clinical
      signs included vomiting, diarrhea, blindness, and lameness. Less than half of the
      cats had clinical evidence of pulmonary disease on admission. Anemia and
      hypoalbuminemia were common laboratory abnormalities. An interstitial pattern was
      the most common radiographic pattern observed with pulmonary disease. Diagnosis
      was based on identification of the organism on cytology or histopathology.
      Fifteen of the 22 cats were treated, and itraconazole was the most common
      antifungal agent prescribed. Median duration of the antifungal treatment was 5 mo
      for cats that survived to discharge. Overall survival at time of discharge for
      cats in this study was 55%.

PMID- 22474047
TI  - Insulinoma in dogs: a review.
AB  - Insulinomas are rare malignant functional pancreatic tumors of the beta cells
      that retain the ability to produce and secrete insulin. Insulinomas are the most
      common pancreatic neuroendocrine tumor in dogs that can induce a variety of
      clinical signs that result from hypoglycemia and secondary neuroglycopenic and
      adrenergic effects. Diagnosis and treatment is considered challenging, and the
      prognosis can be extremely variable depending on the therapeutic choices. This
      review aims to summarize and update classic knowledge with current trends in the
      diagnosis, treatment, and prognosis of insulinomas.

PMID- 22474048
TI  - Surgical management of a subepiglottic thyroglossal duct cyst in a dog.
AB  - A 2 yr old dog presented for dysphagia and coughing secondary to a 4 cm * 4 cm
      turgid subepiglottic mass. Cervical radiographs, an esophagram, and computed
      tomography confirmed the presence of a cystic mass that was not intimately
      associated with any surrounding structures. An incisional biopsy confirmed the
      cystic nature of the mass and helped to rule out a malignancy. A marginal
      surgical excision was performed via a ventral approach. Histopathology of the
      mass was consistent with a thyroglossal duct cyst. This is the first report of a
      thyroglossal duct cyst in this location in a dog. There was no recurrence of
      clinical signs 14 mo after surgery.

PMID- 22474049
TI  - Ectopic pregnancy in an apparently healthy bitch.
AB  - This case describes an extrauterine fetus that was discovered in an apparently
      healthy bitch 5 mo after whelping. The extrauterine fetus was surgically removed,
      and the bitch made a complete recovery. The topic of canine ectopic pregnancy is
      discussed, and a review of previously reported cases is presented.

PMID- 22474050
TI  - Cytologic diagnosis of disseminated histoplasmosis in the wall of the urinary
      bladder of a cat.
AB  - A 10 yr old domestic longhair presented with a 2.5 mo history of recurrent
      hematuria. Abdominal ultrasound examination demonstrated a thickened urinary
      bladder, abdominal lymphadenopathy, and a thickened and rounded spleen. Cytologic
      examination of fine-needle aspirate samples revealed Histoplasma capsulatum
      organisms in the urinary bladder wall and spleen. The cat was treated with
      itraconazole (10 mg/kg per os q 24 hr for 2.5 wk). The cat was euthanized after
      19 days of treatment because of lack of improvement. To the authors' knowledge,
      this is the first documented case of feline disseminated histoplasmosis diagnosed
      in the urinary bladder wall.

PMID- 22474051
TI  - Osteosarcoma of the tibia 6 years after tibial plateau leveling osteotomy.
AB  - A 7 yr old spayed female mastiff presented for examination of a left pelvic limb
      lameness of 3 mo duration. Six years previously, the dog had undergone tibial
      plateau leveling osteotomy (TPLO) surgery of the left pelvic limb for the
      treatment of cranial cruciate disease. On presentation, the dog had a painful and
      swollen proximal tibia. Following investigation, a diagnosis of osteosarcoma of
      the proximal left tibia at the site of the previous TPLO surgery was made. This
      is the first reported case of osteosarcoma following TPLO using an implant other
      than the Slocum plate.

PMID- 22474052
TI  - The use of vacuum-assisted closure in the management of septic peritonitis in six
      dogs.
AB  - The purpose of this study was to describe the appropriate surgical technique,
      postoperative monitoring, and complications encountered with use of vacuum
      assisted closure (VAC) in six dogs with confirmed septic peritonitis. Initial
      diagnosis of septic peritonitis was performed by measuring either the blood-to
      fluid lactate ratio and glucose concentration differences or cytologic
      verification of intracellular bacteria. After appropriate surgical procedures
      were performed to manage the primary cause of peritoneal sepsis, a VAC was
      performed. Serum and abdominal fluid protein levels were measured, and all
      complications were noted during the postoperative period. Three of the six dogs
      (50%) survived to the secondary closure and were subsequent discharged, which is
      similar to previous studies where the abdomen was either closed primarily or
      treated with open abdominal drainage. No major complications occurred with
      bandage management during hospitalization. The results of this study support VAC
      as a feasible technique for managing septic peritonitis.

PMID- 22474053
TI  - Use of terbinafine in the treatment protocol of intestinal Cryptococcus
      neoformans in a dog.
AB  - A 2.5 yr old sexually intact male vizsla was admitted to the Iowa State
      University Veterinary Teaching Hospital for persistent diarrhea, weight loss, and
      panhypoproteinemia. Examination revealed an emaciated condition and melena. Two
      masses were palpated in the cranial abdomen. Hematology and serum biochemistry
      exhibited a regenerative anemia and confirmed the presence of panhypoproteinemia,
      suggestive of a protein-losing eneteropathy. Distinct areas of thickened
      intestinal wall and enlarged mesenteric lymph nodes were found on abdominal
      ultrasound. Cytology from those nodes showed the presence of suspected
      Cryptococcus spp., and infection was confirmed utilizing a cryptococcal antigen
      titer. Medical therapy with lipid-complexed amphotericin B and fluconazole was
      unsuccessful. Two surgical procedures were performed to remove the affected areas
      of intestine and lymph nodes, but the disease persisted as evidenced by a
      persistently elevated cryptococcal antigen titer. Terbinafine was prescribed,
      which resulted in complete resolution of clinical signs and a steadily decreasing
      cryptococcal antigen titer. Very few cases of intestinal cryptococcosis have been
      reported. In this case, infection resulted in a protein-losing enteropathy. In
      addition, this article describes the use of terbinafine in the treatment of
      intestinal cryptococcal infection in the dog, which has not been previously
      reported.

PMID- 22474054
TI  - Making the decision for home hospice: perspectives of bereaved Japanese families
      who had loved ones in home hospice.
AB  - OBJECTIVE: The aim of the study was to evaluate whether family members believed
      that the decision for home hospice had been the acceptable choice and to identify
      factors related to families accepting that the decision was good. METHODS: In
      June 2007, a cross-sectional anonymous questionnaire was distributed to bereaved
      family members of terminal cancer patients in Japan who died at home in the
      previous 6 months. The questionnaire included questions about whether the family
      member believed that the decision for home hospice had been the acceptable choice
      and the decision-making process. RESULTS: A total of 286 responses from 14 home
      hospices were analyzed. A total of 92% of the participants indicated that the
      decision for home hospice had been the acceptable choice. Multivariate logistic
      regression analysis indicated that the following subjects were more likely to
      believe that the decision for home hospice had been the acceptable choice: those
      who (i) considered the patient's desire ahead of the family situation (P <
      0.001); (ii) decided based on knowledge of all options (P < 0.001); (iii) decided
      based on agreement with patient, family and medical staff (P = 0.007); (iv)
      decided based on the patient and family only (P = 0.026); and (v) had patients
      who were enrolled in home hospice for <60 days (P = 0.032). CONCLUSIONS: It is
      important to encourage discussion about end-of-life care and to assist the
      patient and family in the decision-making process by providing information on all
      available options through open communication.

PMID- 22474055
TI  - Assessment of exposure of metabolites in preclinical species and humans at steady
      state from the single-dose radiolabeled absorption, distribution, metabolism, and
      excretion studies: a case study.
AB  - The exposure of a drug candidate and its metabolites in humans and preclinical
      species during drug development needs to be determined to ensure that the safety
      of drug-related components in humans is adequately assessed in the standard
      toxicology studies. The in vivo radiolabeled studies in preclinical species and
      human volunteers provide the total fate of the drug-derived radioactivity
      including the relative abundance of metabolites. Here, we describe how the single
      dose radiolabeled human studies could provide the exposure of circulating
      metabolites at steady state using a case study of an extensively metabolized
      drug, lixivaptan. After an oral dose of [(14)C]lixivaptan to humans, a total of
      nine metabolites were detected in the systemic circulation; eight of them
      exceeded 10% of the parent exposure (2-41% of total radioactivity). The plasma
      samples were profiled for all subjects at each time point by high-performance
      liquid chromatography, and metabolites were quantified using a radioactive
      detector. On the basis of single-dose area under the concentration-time curve
      (AUC) values, exposure of six human metabolites was greater at least in one
      preclinical species used in toxicology evaluation. On the basis of the t(1/2) of
      lixivaptan and two major metabolites from a single dose in humans, their AUC and
      C(max) values were simulated at the steady state. The simulated exposure (C(max)
      and AUC) values of parent drug and the two most abundant metabolites were similar
      to those from a 7-day clinical study obtained using a validated liquid
      chromatography-mass spectrometry assay, suggesting that a well designed single
      dose radiolabeled human study can help in addressing the metabolites in safety
      testing-related issues.

PMID- 22474056
TI  - The pediatric stroke outcome measure: a validation and reliability study.
AB  - BACKGROUND AND PURPOSE: The Pediatric Stroke Outcome Measure (PSOM) is an
      objective, disease-specific outcome measure containing 115 test items suitable
      for newborn to adult ages. The PSOM measures neurological deficit and function
      across 5 subscales: right sensorimotor, left sensorimotor, language production,
      language comprehension, and cognitive/behavior yielding a final 10-point deficit
      score. The goal of this study was to examine PSOM construct validity in measuring
      neurological outcome in pediatric stroke survivors and interrater reliability
      (IRR) for both prospective and retrospective scoring. METHODS: For construct
      validity, PSOM subscale scores were correlated with scores on standardized
      neuropsychological measures matched by functional domain. We assessed IRR by
      comparing same-day "live" PSOM scores from 2 independent raters in 10 children
      (prospective IRR) and by comparing PSOM scores estimated from medical dictations
      across 5 raters in another 10 children (retrospective IRR). RESULTS: We analyzed
      PSOM scores from 203 children with ischemic stroke. PSOM subscales show good
      construct validity (rho=0.2-0.4; P<0.05). PSOM subscale scores of normal/abnormal
      demonstrate strong agreement for domain-matched neuropsychology scores
      (alternative chance-corrected statistic=0.4-0.8). IRR was excellent with the 2
      prospective raters' scores in almost perfect agreement (intraclass correlation
      coefficient, 0.93; 95% CI, 0.76-0.98). Retrospective IRR demonstrated strong
      agreement with an intraclass correlation coefficient of 0.77 (95% CI, 0.56-0.92).
      CONCLUSIONS: The PSOM is a valid and reliable outcome measure for pediatric
      stroke. It is useful for retrospective scoring from health records and
      prospective serial longitudinal outcome assessments and is ideally suited for
      prospective clinical trials in pediatric stroke.

PMID- 22474057
TI  - Treatment with B vitamins and incidence of cancer in patients with previous
      stroke or transient ischemic attack: results of a randomized placebo-controlled
      trial.
AB  - BACKGROUND AND PURPOSE: To determine the effect of B vitamin treatment on the
      incidence of cancer among patients with stroke or transient ischemic attack.
      METHODS: A total of 8164 patients with recent stroke or transient ischemic attack
      were randomly allocated to double-blind treatment with 1 tablet daily of placebo
      or B vitamins (2 mg folic acid, 25 mg vitamin B(6), 500 MUg vitamin B(12)) and
      followed for a median of 3.4 years for any cancer as an adverse event. RESULTS:
      There was no significant difference in the incidence of any cancer among
      participants assigned B vitamins compared with placebo (4.04% versus 4.59%; risk
      ratio, 0.86; 95% CI, 0.70-1.07) and no difference in cancer mortality (2.35%
      versus 2.09%; risk ratio, 1.09; 0.81-1.46). Among 1899 patients with diabetes,
      the incidence of cancer was higher among participants assigned B vitamins
      compared with placebo (5.35% versus 3.28%; adjusted risk ratio, 2.21; 1.31-3.73),
      whereas among 6168 patients without diabetes, the incidence of cancer was lower
      among participants assigned B vitamins compared with placebo (3.66% versus 5.03%;
      adjusted risk ratio, 0.67; 0.51-0.87; P for interaction=0.0001). CONCLUSIONS:
      Daily administration of folic acid, vitamin B(6), and vitamin B(12) to 8164
      patients with recent stroke or transient ischemic attack for a median of 3.4
      years had no significant effect, compared with placebo, on cancer incidence or
      mortality. However, a post hoc subgroup analysis raises the hypothesis that folic
      acid treatment may increase the incidence of cancer among diabetics and reduce
      the incidence of cancer among nondiabetics with a history of stroke or transient
      ischemic attack.

PMID- 22474058
TI  - Automated perfusion imaging for the evaluation of transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is recommended for the
      evaluation of transient ischemic attack. Perfusion imaging can increase the yield
      of MRI in transient ischemic attack. We evaluated automated bolus perfusion (the
      time when the residue function reaches its maximum [TMax] and mean transit time
      [MTT]) and arterial spin labeling (ASL) sequences for the detection of ischemic
      lesions in patients with transient ischemic attack. METHODS: We enrolled
      consecutive patients evaluated for suspicion of acute transient ischemic attack
      by multimodal MRI within 36 hours of symptom onset. Two independent raters
      assessed the presence and location of ischemic lesions blinded to the clinical
      presentation. The prevalence of ischemic lesions and the interrater agreement
      were 1,410 assessed. RESULTS: From January 2010 to 2011, 93 patients were
      enrolled and 90 underwent perfusion imaging (69 bolus perfusion and 76 ASL).
      Overall, 25 of 93 patients (27%) were DWI-positive and 14 (15%) were perfusion
      positive but DWI-negative (ASL n=9; TMax n=9; MTT n=2). MTT revealed an ischemic
      lesion in fewer patients than TMax (7 versus 20, P=0.004). Raters agreed on 89%
      of diffusion-weighted imaging cases, 89% of TMax, 87% o10f010 MTT, and 90% of ASL
      cases. The interrater agreement was good for DWI, TMax, and ASL (kappa=0.73,
      0.72, and 0.74, respectively) and fair for MTT (kappa=0.43). Diffusion and/or
      perfusion were positive in 39 of 69 (57%) patients with a discharge diagnosis of
      possible ischemic event. CONCLUSIONS: Our results suggest that in patients
      referred for suspicion of transient ischemic attack, automated TMax is more
      sensitive than MTT, and both ASL and TMax increase the yield of MRI for the
      detection of ischemic lesions.

PMID- 22474059
TI  - Resolution of intraventricular hemorrhage varies by ventricular region and dose
      of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated
      Resolution of IVH (CLEAR IVH) program.
AB  - BACKGROUND AND PURPOSE: The Clot Lysis: Evaluating Accelerated Resolution of IVH
      (CLEAR IVH) program is assessing the efficacy of intraventricular recombinant
      tissue-type plasminogen activator (rtPA) for spontaneous intraventricular
      hemorrhage (IVH). This subanalysis assesses the effect of dose of rtPA by region
      on clearance of IVH. METHODS: Sixty-four patients within 12 to 24 hours of
      spontaneous IVH were randomized to placebo or 0.3 mg, 1 mg, or 3 mg of rtPA twice
      daily through an extraventricular drain. Twelve subregions of the ventricles were
      scored from 0 to 4. Effect of dose on IVH clearance to 50% of baseline score was
      compared by survival analysis for all regions combined and by subregion. Models
      including ventricular region, dose, and baseline score were compared by Cox
      proportional hazards. RESULTS: IVH score reduced faster across all regions with
      increasing rtPA dose (clearance to 50%: log-rank P<0.0001; placebo-11.43 days,
      95% CI, 5.68-17.18; 0.3 mg-3.19 days, 1.00-5.38; 1 mg-3.54 days, 0.45-6.64; 3 mg
      2.59 days, 1.72-3.46). In the combined models, dose and baseline score were
      independently associated with reduction in IVH score, which was quickest in the
      midline ventricles, then the anterior half of the lateral ventricles and slowest
      in the posterior half of the lateral ventricles (clearance to 50%: P<0.0001; rtPA
      dose: hazard ratio, 1.47, 1.30-1.67; midline versus anterolateral hazard ratio,
      1.71, 1.08-2.71; midline versus posterolateral hazard ratio, 4.05, 2.46-6.65;
      baseline score hazard ratio, 0.96, 0.91-1.01) with a significant interaction
      between dose and ventricular region (P=0.005). CONCLUSIONS: rtPA accelerates
      resolution of IVH. This effect is dose-dependent, is greatest in the midline
      ventricles, and least in the posterolateral ventricles.

PMID- 22474060
TI  - Vascular occlusion enables selecting acute ischemic stroke patients for treatment
      with desmoteplase.
AB  - BACKGROUND AND PURPOSE: Desmoteplase is a novel and highly fibrin-specific
      thrombolytic agent. Evidence of safety and efficacy was obtained in 2 phase II
      trials (Desmoteplase In Acute Ischemic Stroke [DIAS] and Desmoteplase for Acute
      Ischemic Stroke [DEDAS]). The DIAS-2 phase III trial did not replicate the
      positive phase II efficacy findings. Post hoc analyses were performed with the
      aim of predicting treatment responders based on CTA and MRA. METHODS: Patients
      were grouped according to vessel status (Thrombolysis In Myocardial Infarction
      [TIMI] grade) for logistic regression of clinical response, applying the data
      from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2. RESULTS: In
      DIAS-2, a substantial number of mismatch-selected patients (126/179; 70%)
      presented with a normal flow/low-grade stenosis (TIMI 2-3) at screening, with the
      majority having a favorable outcome at day 90. In contrast, favorable outcome
      rates in patients with vessel occlusion/high-grade stenosis (TIMI 0-1) were 18%
      with placebo versus 36% and 27% with desmoteplase 90 and 125 MUg/kg,
      respectively. The clinical effect based on the pooled data from DIAS, DEDAS, and
      DIAS-2 was favorable for desmoteplase-treated patients presenting with TIMI 0 to
      1 at baseline (OR, 4.144; 95% CI, 1.40-12.23; P=0.010). There was no desmoteplase
      treatment benefit in patients presenting with TIMI 2 to 3 (OR, 1.109).
      CONCLUSIONS: In this sample of patients with a mismatch diagnosed, proximal
      vessel occlusion or severe stenosis was associated with clinically beneficial
      treatment effects of desmoteplase. Selecting patients using CTA or MRA in
      clinical trials of thrombolytic therapy is justifiable.

PMID- 22474063
TI  - Nasal intermittent positive-pressure ventilation vs nasal continuous positive
      airway pressure for preterm infants with respiratory distress syndrome: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To determine among preterm infants with respiratory distress syndrome
      whether the use of early nasal intermittent positive-pressure ventilation (NIPPV)
      vs nasal continuous positive airway pressure (NCPAP) decreases the need for
      invasive ventilation within the first 72 hours of life. DATA SOURCES: MEDLINE,
      EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and
      clinicaltrials.gov were searched, as well as abstracts from meetings of the
      Pediatric Academic Societies. STUDY SELECTION: Randomized controlled trials
      involving infants with respiratory distress syndrome who received NIPPV vs NCPAP.
      DATA EXTRACTION: Data were extracted on the use of NIPPV vs NCPAP. Also extracted
      were data on the need for invasive ventilation within the first 72 hours of life
      and the incidences of bronchopulmonary dysplasia, pneumothorax, necrotizing
      enterocolitis, and intraventricular hemorrhage, as well as the time to full feeds
      and the duration of hospital stay. DATA SYNTHESIS: Three trials were included (n
      = 360). A significant decrease in the need for invasive ventilation was found in
      the NIPPV group (risk ratio, 0.60; 95% CI, 0.43-0.83). No difference between
      groups was found in the incidence of bronchopulmonary dysplasia (risk ratio,
      0.56; 95% CI, 0.09-3.49). No differences in the other outcomes were observed
      between the 2 groups. CONCLUSIONS: Among preterm infants with respiratory
      distress syndrome, NIPPV decreases the need for invasive ventilation within the
      first 72 hours of life compared with NCPAP. Trials are needed to assess whether
      NIPPV minimizes the occurrence of bronchopulmonary dysplasia and other
      comorbidities.

PMID- 22474061
TI  - Genome analysis of the domestic dog (Korean Jindo) by massively parallel
      sequencing.
AB  - Although pioneering sequencing projects have shed light on the boxer and poodle
      genomes, a number of challenges need to be met before the sequencing and
      annotation of the dog genome can be considered complete. Here, we present the DNA
      sequence of the Jindo dog genome, sequenced to 45-fold average coverage using
      Illumina massively parallel sequencing technology. A comparison of the sequence
      to the reference boxer genome led to the identification of 4 675 437 single
      nucleotide polymorphisms (SNPs, including 3 346 058 novel SNPs), 71 642 indels
      and 8131 structural variations. Of these, 339 non-synonymous SNPs and 3 indels
      are located within coding sequences (CDS). In particular, 3 non-synonymous SNPs
      and a 26-bp deletion occur in the TCOF1 locus, implying that the difference
      observed in cranial facial morphology between Jindo and boxer dogs might be
      influenced by those variations. Through the annotation of the Jindo olfactory
      receptor gene family, we found 2 unique olfactory receptor genes and 236
      olfactory receptor genes harbouring non-synonymous homozygous SNPs that are
      likely to affect smelling capability. In addition, we determined the DNA sequence
      of the Jindo dog mitochondrial genome and identified Jindo dog-specific mtDNA
      genotypes. This Jindo genome data upgrade our understanding of dog genomic
      architecture and will be a very valuable resource for investigating not only dog
      genetics and genomics but also human and dog disease genetics and comparative
      genomics.

PMID- 22474064
TI  - Picture of the month. Palmoplantar psoriasis.

PMID- 22474065
TI  - Youth sports and concussion risk.

PMID- 22474066
TI  - Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB
      48 metabolism.
AB  - Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL
      cholesteryl ester to triglyceride-rich lipoproteins (TRL). This study aimed to
      determine the effects of CETP inhibition with torcetrapib on TRL composition and
      apoB-48 metabolism. Study subjects with low HDL cholesterol (<40 mg/dl), either
      untreated (n = 9) or receiving atorvastatin 20 mg daily (n = 9), received placebo
      for 4 weeks, followed by torcetrapib 120 mg once daily for the next 4 weeks. A
      subset of the subjects not treated with atorvastatin participated in a third
      phase (n = 6), in which they received torcetrapib 120 mg twice daily for an
      additional 4 weeks. At the end of each phase, all subjects received a primed
      constant infusion of [5,5,5-(2)H(3)]L-leucine, while in the constantly fed state,
      to determine the kinetics of TRL apoB-48 and TRL composition. Relative to
      placebo, torcetrapib markedly reduced TRL CE levels in all groups (>=-69%; P <
      0.005). ApoB-48 pool size (PS) and production rate (PR) decreased in the
      nonatorvastatin once daily (PS: -49%, P = 0.007; PR: -49%, P = 0.005) and twice
      daily (PS: -30%, P = 0.01; PR: -27%, P = 0.13) cohorts. In the atorvastatin
      cohort, apoB-48 PS and PR, which were already lowered by atorvastatin, did not
      change with torcetrapib. Our findings indicate that CETP inhibition reduced
      plasma apoB-48 concentrations by reducing apoB-48 production but did not have
      this effect in subjects already treated with atorvastatin.

PMID- 22474067
TI  - Constitutive inhibition of plasma CETP by apolipoprotein C1 is blunted in
      dyslipidemic patients with coronary artery disease.
AB  - Plasma cholesteryl ester transfer protein (CETP) promotes the cholesterol
      enrichment of apoB-containing lipoproteins (VLDL and LDL) at the expense of HDL.
      Recent studies demonstrated that apoC1 is a potent CETP inhibitor in plasma of
      healthy, normolipidemic subjects. Our goal was to establish whether the
      modulation of CETP activity by apoC1 is influenced by dyslipidemia in patients
      with documented coronary artery disease (CAD). In the total CAD population
      studied (n = 240), apoC1 levels correlated negatively with CETP activity,
      independently of apoE-epsilon, CETP-Taq1B, and apoC1-Hpa1 genotypes. In
      multivariate analysis, the negative relationship was observed only in
      normolipidemic patients, not in those with hypercholesterolemia,
      hypertriglyceridemia, or combined hyperlipidemia. In the normolipidemic subjects,
      apoC1 levels were positively associated with higher HDL- to LDL-cholesterol ratio
      (r = 0.359, P < 0.001). It is concluded that apoC1 as a CETP inhibitor no longer
      operates on cholesterol redistribution in high-risk patients with dyslipidemia,
      probably due to increasing amounts of VLDL-bound apoC1, which is inactive as a
      CETP inhibitor. Patients with dyslipidemia could experience major benefits from
      treatment with pharmacological CETP inhibitors, which might compensate for
      blunted endogenous inhibition.

PMID- 22474068
TI  - Seipin: from human disease to molecular mechanism.
AB  - The most-severe form of congenital generalized lipodystrophy (CGL) is caused by
      mutations in BSCL2/seipin. Seipin is a homo-oligomeric integral membrane protein
      in the endoplasmic reticulum that concentrates at junctions with cytoplasmic
      lipid droplets (LDs). While null mutations in seipin are responsible for
      lipodystrophy, dominant mutations cause peripheral neuropathy and other nervous
      system pathologies. We first review the clinical aspects of CGL and the discovery
      of the responsible genetic loci. The structure of seipin, its normal isoforms,
      and mutations found in patients are then presented. While the function of seipin
      is not clear, seipin gene manipulation in yeast, flies, mice, and human cells has
      recently yielded a trove of information that suggests roles in lipid metabolism
      and LD assembly and maintenance. A model is presented that attempts to bridge
      these new data to understand the role of this fascinating protein.

PMID- 22474069
TI  - Toward individualized breast cancer therapy: translating biological concepts to
      the bedside.
AB  - The management of breast cancer has changed dramatically over the past 20 years.
      Based on gene expression profiles, or proteomics of three or four biomarkers, it
      is apparent that there are multiple subtypes with different clinical
      characteristics, clinical courses, and sensitivities to existing therapies. This
      manuscript reviews the management of hormone receptor-positive, human epidermal
      growth factor receptor 2-positive, and triple-negative breast cancers,
      emphasizing changes that have occurred in recent years and focusing on potential
      mechanisms of drug resistance. I also highlight strategies to prevent or overcome
      resistance to specific therapeutic agents. As a result of enhanced biological
      understanding of the molecular anomalies that drive the development, progression,
      and dissemination of breast cancer, a number of novel, molecularly targeted
      agents have been added to standard therapies. Chemotherapy, endocrine therapy,
      and targeted treatments have markedly reduced the risk for recurrence and
      mortality after primary treatment of breast cancer and have increased the 5- and
      10-year survival rates. The challenges with novel therapeutics include the
      absence of accurate predictive biomarkers to identify those patient who will
      derive substantial benefit and those patients whose tumors are resistant to
      specific antitumor agents. As we move forward with increasing molecular
      segmentation of breast cancer and develop new, highly targeted agents, molecular
      diagnostics must accompany molecular therapeutics to implement the concept of
      personalized cancer therapy.

PMID- 22474070
TI  - The nature of dopamine dysfunction in schizophrenia and what this means for
      treatment.
AB  - CONTEXT: Current drug treatments for schizophrenia are inadequate for many
      patients, and despite 5 decades of drug discovery, all of the treatments rely on
      the same mechanism: dopamine D(2) receptor blockade. Understanding the
      pathophysiology of the disorder is thus likely to be critical to the rational
      development of new treatments for schizophrenia. OBJECTIVE: To investigate the
      nature of the dopaminergic dysfunction in schizophrenia using meta-analysis of in
      vivo studies. DATA SOURCES: The MEDLINE, EMBASE, and PsycINFO databases were
      searched for studies from January 1, 1960, to July 1, 2011. STUDY SELECTION: A
      total of 44 studies were identified that compared 618 patients with schizophrenia
      with 606 controls, using positron emission tomography or single-photon emission
      computed tomography to measure in vivo striatal dopaminergic function. DATA
      EXTRACTION: Demographic, clinical, and imaging variables were extracted from each
      study, and effect sizes were determined for the measures of dopaminergic
      function. Studies were grouped into those of presynaptic function and those of
      dopamine transporter and receptor availability. Sensitivity analyses were
      conducted to explore the consistency of effects and the effect of clinical and
      imaging variables. DATA SYNTHESIS: There was a highly significant elevation
      (P.<001) in presynaptic dopaminergic function in schizophrenia with a large
      effect size (Cohen d=0.79). There was no evidence of alterations in dopamine
      transporter availability. There was a small elevation in D(2/3) receptor
      availability (Cohen d=0.26), but this was not evident in drug-naive patients and
      was influenced by the imaging approach used. CONCLUSIONS: The locus of the
      largest dopaminergic abnormality in schizophrenia is presynaptic, which affects
      dopamine synthesis capacity, baseline synaptic dopamine levels, and dopamine
      release. Current drug treatments, which primarily act at D(2/3) receptors, fail
      to target these abnormalities. Future drug development should focus on the
      control of presynaptic dopamine synthesis and release capacity.

PMID- 22474071
TI  - Reduced natural oscillatory frequency of frontal thalamocortical circuits in
      schizophrenia.
AB  - CONTEXT: Converging evidence from electrophysiological studies suggests that in
      individuals with schizophrenia, electroencephalographic frontal fast oscillations
      are reduced. It is still unclear whether this reduction reflects an intrinsic
      deficit of underlying cortical/thalamocortical circuits and whether this deficit
      is specific for frontal regions. Recent electrophysiological studies in healthy
      individuals have established that, when perturbed, different brain regions
      oscillate at a specific, intrinsically generated dominant frequency, the natural
      frequency. OBJECTIVE: To assess the natural frequency of the posterior parietal,
      motor, premotor, and prefrontal cortices in patients with schizophrenia and
      healthy control subjects. DESIGN: High-density electroencephalographic recordings
      during transcranial magnetic stimulation of 4 cortical areas were performed.
      Several transcranial magnetic stimulation-evoked electroencephalographic
      oscillation parameters, including synchronization, amplitude, and natural
      frequency, were compared across the schizophrenia and healthy control groups.
      SETTING: Wisconsin Psychiatric Institute and Clinic, University of Wisconsin
      Madison. PARTICIPANTS: Twenty patients with schizophrenia and 20 age-matched
      healthy control subjects. MAIN OUTCOME MEASURES: High-density
      electroencephalographic measurements of transcranial magnetic stimulation-evoked
      activity in 4 cortical areas, scores on the Positive and Negative Syndrome Scale,
      and performance scores (reaction time, accuracy) on 2 computerized tasks (word
      memory [Penn Word Recognition Test] and facial memory [Penn Facial Memory Test]).
      RESULTS: Patients with schizophrenia showed a slowing in the natural frequency of
      the frontal/prefrontal regions compared with healthy control subjects (from an
      average of a 2-Hz decrease for the motor area to an almost 10-Hz decrease for the
      prefrontal cortex). The prefrontal natural frequency of individuals with
      schizophrenia was slower than in any healthy comparison subject and correlated
      with both positive Positive and Negative Syndrome Scale scores and reaction time
      on the Penn Word Recognition Test. CONCLUSIONS: These findings suggest that
      patients with schizophrenia have an intrinsic slowing in the natural frequency of
      frontal cortical/thalamocortical circuits, that this slowing is not present in
      parietal areas, and that the prefrontal natural frequency can predict some of the
      symptoms as well as the cognitive dysfunctions of schizophrenia.

PMID- 22474072
TI  - Prenatal antipsychotic exposure and neuromotor performance during infancy.
AB  - CONTEXT: Despite the expanding clinical utility of antipsychotics beyond
      psychotic disorders to include depressive, bipolar, and anxiety disorders,
      reproductive safety data regarding the neurodevelopmental sequelae of fetal
      antipsychotic exposure are scarce. OBJECTIVE: To examine whether intrauterine
      antipsychotic exposure is associated with deficits in neuromotor performance and
      habituation in 6-month-old infants. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective controlled study was conducted from December 1999 through June 2008
      at the Infant Development Laboratory of the Emory Psychological Center examining
      maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to
      antipsychotics (n=22), antidepressants (n=202), or no psychotropic agents (n=85).
      Examiners masked to maternal-infant exposure status administered a standardized
      neuromotor examination (Infant Neurological International Battery [INFANIB]) that
      tests posture, tone, reflexes, and motor skills and a visual habituation paradigm
      using a neutral female face. MAIN OUTCOME MEASURES: The INFANIB composite score;
      number of trials required to achieve a 50% decrease in infant fixation during a
      visual habituation task; and mean time looking at the stimulus across 10 trials.
      RESULTS: Infants prenatally exposed to antipsychotics (mean=64.71) showed
      significantly lower INFANIB scores than those with antidepressant (mean=68.57) or
      no psychotropic (mean=71.19) exposure, after controlling for significant
      covariates (F(2,281)=4.51; P=.01; partial eta(2)=0.033). The INFANIB scores were
      also significantly associated with maternal psychiatric history, including
      depression, psychosis, and overall severity/chronicity (P's.05) and maternal
      depression during pregnancy was associated with less efficient habituation
      (r(245)=0.16; P.02). There were no significant differences regarding habituation
      between medication exposure groups. CONCLUSIONS: Among 6-month-old infants, a
      history of intrauterine antipsychotic exposure, compared with antidepressant or
      no psychotropic exposure, was associated with significantly lower scores on a
      standard test of neuromotor performance, highlighting the need for further
      scrutiny of the reproductive safety and neurodevelopmental sequelae of fetal
      antipsychotic exposure. Disentangling medication effects from maternal illness
      effects, which also contributed, remains a critical challenge.

PMID- 22474073
TI  - Hydrogen sulfide induced disruption of Na+ homeostasis in the cortex.
AB  - Maintenance of ionic balance is essential for neuronal functioning. Hydrogen
      sulfide (H(2)S), a known toxic environmental gaseous pollutant, has been recently
      recognized as a gasotransmitter involved in numerous biological processes and is
      believed to play an important role in the neural activities under both
      physiological and pathological conditions. However, it is unclear if it plays any
      role in maintenance of ionic homeostasis in the brain under
      physiological/pathophysiological conditions. Here, we report by directly
      measuring Na(+) activity using Na(+) selective electrodes in mouse cortical
      slices that H(2)S donor sodium hydrosulfide (NaHS) increased Na(+) influx in a
      concentration-dependent manner. This effect could be partially blocked by either
      Na(+) channel blocker or N-methyl-D-aspartate receptor (NMDAR) blocker alone or
      almost completely abolished by coapplication of both blockers but not by non
      NMDAR blocker. These data suggest that increased H(2)S in pathophysiological
      conditions, e.g., hypoxia/ischemia, potentially causes a disruption of ionic
      homeostasis by massive Na(+) influx through Na(+) channels and NMDARs, thus
      injuring neural functions. Activation of delta-opioid receptors (DOR), which
      reduces Na(+) currents/influx in normoxia, had no effect on H(2)S-induced Na(+)
      influx, suggesting that H(2)S-induced disruption of Na(+) homeostasis is
      resistant to DOR regulation and may play a major role in neuronal injury in
      pathophysiological conditions, e.g., hypoxia/ischemia.

PMID- 22474074
TI  - Small interfering RNA-mediated knockdown of protein kinase C zeta attenuates
      domoic acid-induced cognitive deficits in mice.
AB  - Accumulated evidence indicates that domoic acid (DA)-induced excitatory neuronal
      injury is associated with excessive reactive oxygen species (ROS) production.
      Protein kinase C zeta (PKC-zeta)/nicotinamide adenine dinucleotide phosphate
      (NOX) signaling regulates ROS levels and is involved in various neurodegenerative
      disorders including excitoneurotoxicity. Our previous studies have demonstrated
      that ROS-induced activation of the stress-activated protein kinase/c-jun-N
      terminal kinase (SAPK/JNK) pathway plays a key role in the pathogenesis of
      cognitive deficits induced by DA. However, the precise biological mechanisms
      underlying these effects are not well understood. In this study, we investigate
      whether the PKC-zeta mediates DA-induced cognitive deficits and further explored
      the potential molecular processes. DA treatment significantly increased the
      expression of PI3K p85alpha, and PKC-zeta in the hippocampus of mice, which
      promoted the p47phox phosphorylation and expression, enhanced NOX activity, and
      increased the levels of ROS and protein carbonyls. In turn, the abnormal ROS
      levels in the hippocampus of DA-treated mice activated SAPK/JNK pathway,
      decreased FoxO1 phosphorylation, stimulated the nuclear translocation of FoxO1,
      activated FasL/Fas signaling, and promoted the activation of caspase-8 and
      caspase-3, which resulted in neuron apoptosis and cognitive deficits in mice.
      However, PKC-zeta knockdown reversed these changes in mice. It was further
      demonstrated that FoxO1 was a downstream target of SAPK/JNK signaling by FoxO1
      small interfering RNA and SP600125 (an inhibitor of SAPK/JNK pathway) treatment.
      Additionally, SP600125 treatment or FoxO1 knockdown also blocked FasL/Fas
      signaling-dependent apoptosis and improved DA-induced cognitive deficits in the
      hippocampus of mice. These results suggest that PKC-zeta could be a possible
      target for the prevention or treatment of cognitive deficits in excitotoxic and
      other brain disorders.

PMID- 22474075
TI  - Herpes virus deneddylases interrupt the cullin-RING ligase neddylation cycle by
      inhibiting the binding of CAND1.
AB  - The conserved N-terminal domains of the major tegument proteins of herpes viridae
      encode cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase
      activity. Here we show that the Epstein-Barr virus-encoded member of this enzyme
      family, BPLF1, is targeted to cullin-RING ubiquitin ligases (CRLs) via the
      interaction of the conserved helix-2 with helix-23 of the C-terminal domain (CTD)
      of cullins, at a site involved in electrostatic interaction with helix-8 of the
      CRL regulator CAND1. Mutation of the solvent-exposed Asp86 and Asp90 of helix-2
      to Arg does not affect the enzymatic activity of BPLF1 but abolishes cullin
      binding and prevents CRL inactivation. The binding of the catalytically active
      BPLF1 to cullins inhibits the recruitment of CAND1 to the deneddylated CRLs and
      promotes the selective degradation of cullins by the proteasome. Cullin
      proteolysis is rescued by the overexpression of CAND1 or its CTD-binding N
      terminal domain. These findings illustrate a new strategy for viral modulation of
      CRL activity where the combined effects of cullin deneddylation and their
      targeting for proteasomal degradation drive stable inactivation of the ligases.

PMID- 22474076
TI  - HIF-1alpha binding to the Epac1 promoter recruits hematopoietic stem cells to the
      ischemic brain following stroke.

PMID- 22474077
TI  - For people with persistent tension-type neck pain, a multicomponent pain and
      stress self-management intervention gives better improvement in ability to
      control pain and self-efficacy, but not disability, than physical therapy.

PMID- 22474078
TI  - Serial changes in highly sensitive cardiac troponin improve the early diagnosis
      of acute myocardial infarction.

PMID- 22474079
TI  - For women with term low-risk pregnancies, risk of perinatal mortality and
      intrapartum morbidity similar across planned places of birth.

PMID- 22474080
TI  - In China, hospital births are associated with a 62% decreased risk of neonatal
      mortality.

PMID- 22474082
TI  - Suppression of PDGF-induced PI3 kinase activity by imatinib promotes adipogenesis
      and adiponectin secretion.
AB  - Improved glucose and lipid metabolism is a unique side effect of imatinib therapy
      in some chronic myeloid leukaemia (CML) patients. We recently reported that
      plasma levels of adiponectin, an important regulator of insulin sensitivity, are
      elevated following imatinib therapy in CML patients, which could account for
      these improved metabolic outcomes. Adiponectin is secreted exclusively from
      adipocytes, suggesting that imatinib modulates adiponectin levels directly, by
      transcriptional upregulation of adiponectin in pre-existing adipocytes, and/or
      indirectly, by stimulating adipogenesis. In this report, we have demonstrated
      that imatinib promotes adipogenic differentiation of human mesenchymal stromal
      cells (MSCs), which in turn secrete high-molecular-weight adiponectin.
      Conversely, imatinib does not stimulate adiponectin secretion from mature
      adipocytes. We hypothesise that inhibition of PDGFRalpha (PDGFRA) and PDGFRbeta
      (PDGFRB) is the mechanism by which imatinib promotes adipogenesis. Supporting
      this, functional blocking antibodies to PDGFR promote adipogenesis and
      adiponectin secretion in MSC cultures. We have shown that imatinib is a potent
      inhibitor of PDGF-induced PI3 kinase activation and, using a PI3 kinase p110alpha
      specific inhibitor (PIK-75), we have demonstrated that suppression of this
      pathway recapitulates the effects of imatinib on MSC differentiation.
      Furthermore, using mitogens that activate the PI3 kinase pathway, or MSCs
      expressing constitutively activated Akt, we have shown that activation of the PI3
      kinase pathway negates the pro-adipogenic effects of imatinib. Taken together,
      our results suggest that imatinib increases plasma adiponectin levels by
      promoting adipogenesis through the suppression of PI3 kinase signalling
      downstream of PDGFR.

PMID- 22474083
TI  - Umbilical cord stromal cell differentiation: little correlation with known
      markers of the chondrocyte phenotype or cartilage extracellular matrix.

PMID- 22474084
TI  - A highly efficient multifunctional tandem affinity purification approach
      applicable to diverse organisms.
AB  - Determining the localization, binding partners, and secondary modifications of
      individual proteins is crucial for understanding protein function. Several tags
      have been constructed for protein localization or purification under either
      native or denaturing conditions, but few tags permit all three simultaneously.
      Here, we describe a multifunctional tandem affinity purification (MAP) method
      that is both highly efficient and enables protein visualization. The MAP tag
      utilizes affinity tags inserted into an exposed surface loop of mVenus offering
      two advantages: (1) mVenus fluorescence can be used for protein localization or
      FACS-based selection of cell lines; and (2) spatial separation of the affinity
      tags from the protein results in high recovery and reduced variability between
      proteins. MAP purification was highly efficient in multiple organisms for all
      proteins tested. As a test case, MAP combined with liquid chromatography-tandem
      MS identified known and new candidate binding partners and modifications of the
      kinase Plk1. Thus the MAP tag is a new powerful tool for determining protein
      modification, localization, and interactions.

PMID- 22474086
TI  - Strong on vision, flexible on details.

PMID- 22474085
TI  - Mapping the protein interaction network of the human COP9 signalosome complex
      using a label-free QTAX strategy.
AB  - The COP9 signalosome (CSN) is a multi-subunit protein complex that performs
      critical roles in controlling diverse cellular and developmental processes.
      Aberrant regulation of the CSN complex has been shown to lead to tumorigenesis.
      Despite its biological significance, our current knowledge of the function and
      regulation of the CSN complex is very limited. To explore CSN biology, we have
      developed and employed a new version of the tag team-based QTAX strategy
      (quantitative analysis of tandem affinity purified in vivo cross-linked (X)
      protein complexes) by incorporating a label-free MS method for quantitation.
      Coupled with protein interaction network analysis, this strategy produced a
      comprehensive and detailed assessment of the protein interaction network of the
      human CSN complex. In total, we quantitatively characterized 825 putative CSN
      interacting proteins, with 270 classified as core interactors (captured by all
      three bait purifications). Biochemical validation further confirms the validity
      of selected identified interactors. This work presents the most complete analysis
      of the CSN interaction network to date, providing an inclusive set of physical
      interaction data consistent with physiological roles for the CSN. Moreover, the
      methodology described here is a general proteomic tool for the comprehensive
      study of protein interaction networks.

PMID- 22474087
TI  - Hip instability.

PMID- 22474088
TI  - Pediatric cervical spine trauma.

PMID- 22474089
TI  - Radiographic analysis of spondylolisthesis and sagittal spinopelvic deformity.
AB  - Traditional radiographic analysis of spondylolisthesis focuses on the regional
      sagittal deformity at the lumbosacral junction. Pelvic morphology has also been
      cited as an important factor that contributes to the development of high-grade
      spondylolisthesis. However, the importance of global sagittal balance of the
      spine and pelvis in patients with spondylolisthesis has been emphasized recently.
      Patients with this condition can develop abnormal sagittal spinopelvic balance;
      restoration of sagittal spinal alignment can improve their health-related quality
      of life. Reduction has been used to restore alignment, but its role in the
      management of high-grade spondylolisthesis is controversial. None of the current
      classification systems take sagittal sacropelvic and spinopelvic balance into
      account. Improved understanding of the relationship between the spine and pelvis
      has led to the development of a new classification system that incorporates
      analysis of spinopelvic balance in the radiographic assessment. This new system
      may aid surgeons in identifying patients who would benefit from a partial
      reduction procedure.

PMID- 22474090
TI  - Management of pediatric trigger thumb and trigger finger.
AB  - Pediatric trigger thumb and trigger finger represent distinct conditions and
      should not be treated like adult acquired trigger finger. Over the last two
      decades, our understanding of the natural history of pediatric trigger thumb and
      the etiology and surgical management of pediatric trigger finger has improved.
      Pediatric trigger thumb may spontaneously resolve, although resolution may take
      several years. Open surgical release of the A1 pulley of the thumb is an
      alternative option that nearly uniformly restores thumb interphalangeal joint
      motion. Surgical management of pediatric trigger finger with isolated release of
      the A1 pulley has been associated with high recurrence rates. Awareness of the
      anatomic factors that may contribute to triggering in the pediatric finger and
      willingness to explore and address other involved components of the flexor
      mechanism can prevent surgical failure.

PMID- 22474091
TI  - Modularity of the femoral component in total hip arthroplasty.
AB  - Modular femoral components have been developed to aid in recreating native
      femoral version, limb length, and offset in total hip arthroplasty. Use of
      modular implants results in cost savings, as well. Inventory can be reduced while
      allowing intraoperative flexibility and options. With modular implants, the
      femoral prosthesis can be built in situ, which is helpful in minimizing incision
      length and surgical dissection. However, additional modular junctions are
      associated with increased concern for component failure through taper fretting,
      fatigue fracture, and local corrosion, which may contribute to elevated serum
      metal ion levels. The recent trend toward using larger diameter femoral heads may
      impart higher loads and stress than were seen previously. Although modular
      components offer a plethora of intraoperative options in primary and revision
      total hip arthroplasty, the long-term effects of these additional junctions
      remains unknown.

PMID- 22474092
TI  - Medial epicondyle fractures in the pediatric population.
AB  - Humeral medial epicondyle fractures in the pediatric population account for up to
      20% of elbow fractures, 60% of which are associated with elbow dislocation.
      Isolated injuries can occur from either direct trauma or avulsion. Medial
      epicondyle fractures also occur in combination with elbow dislocations.
      Traditional management by cast immobilization increasingly is being replaced with
      early fixation and mobilization. Relative indications for surgical fixation
      include ulnar nerve entrapment, gross elbow instability, and fractures in
      athletic or other patients who require high-demand upper extremity function.
      Absolute indications for surgical intervention are an incarcerated fragment in
      the joint or open fractures. Radiographic assessment of these injuries and their
      true degree of displacement remain controversial.

PMID- 22474093
TI  - Aneurysmal bone cyst.
AB  - Aneurysmal bone cysts are rare skeletal tumors that most commonly occur in the
      first two decades of life. They primarily develop about the knee but may arise in
      any portion of the axial or appendicular skeleton. Pathogenesis of these tumors
      remains controversial and may be vascular, traumatic, or genetic. Radiographic
      features include a dilated, radiolucent lesion typically located within the
      metaphyseal portion of the bone, with fluid-fluid levels visible on MRI.
      Histologic features include blood-filled lakes interposed between fibrous
      stromata. Differential diagnosis includes conditions such as telangiectatic
      osteosarcoma and giant cell tumor. The mainstay of treatment is curettage and
      bone graft, with or without adjuvant treatment. Other management options include
      cryotherapy, sclerotherapy, radionuclide ablation, and en bloc resection. The
      recurrence rate is low after appropriate treatment; however, more than one
      procedure may be required to completely eradicate the lesion.

PMID- 22474094
TI  - The Hill-Sachs lesion: diagnosis, classification, and management.
AB  - The Hill-Sachs lesion is an osseous defect of the humeral head that is typically
      associated with anterior shoulder instability. The incidence of these lesions in
      the setting of glenohumeral instability is relatively high and approaches 100% in
      persons with recurrent anterior shoulder instability. Reverse Hill-Sachs lesion
      has been described in patients with posterior shoulder instability. Glenoid bone
      loss is typically associated with the Hill-Sachs lesion in patients with
      recurrent anterior shoulder instability. The lesion is a bipolar injury, and
      identification of concomitant glenoid bone loss is essential to optimize clinical
      outcome. Other pathology (eg, Bankart tear, labral or capsular injuries) must be
      identified, as well. Treatment is dictated by subjective and objective findings
      of shoulder instability and radiographic findings. Nonsurgical management,
      including focused rehabilitation, is acceptable in cases of small bony defects
      and nonengaging lesions in which the glenohumeral joint remains stable during
      desired activities. Surgical options include arthroscopic and open techniques.

PMID- 22474095
TI  - Management of calcaneal tuberosity fractures.
AB  - Fractures of the calcaneal tuberosity are relatively uncommon and are seen most
      frequently in elderly and diabetic patients. These injuries are typically
      avulsion fractures caused by concentric contraction of the gastrocnemius-soleus
      muscle complex. Displacement of these fractures can compromise the skin over the
      posterior aspect of the heel; therefore, early recognition and management are
      imperative. Surgical management of calcaneal tuberosity fractures requires
      reduction and stable fixation of the displaced fragment. When the patient has
      preexisting tightness of the gastrocnemius-soleus complex, successful management
      must also address this pathology to improve outcome.

PMID- 22474096
TI  - Osteoarthritis and metabolic syndrome.

PMID- 22474097
TI  - Autophagy: a new therapeutic target in cartilage injury and osteoarthritis.

PMID- 22474098
TI  - The first lady almoner: the appointment, position, and findings of Miss Mary
      Stewart at the Royal Free Hospital, 1895-99.
AB  - This article examines the professional roots of the hospital almoner, a position
      which has been widely neglected in medical history. The first almoner was Miss
      Mary Stewart, a former Charity Organization Society employee, appointed at the
      Royal Free Hospital of central London in 1895. The Royal Free was a charitable
      hospital which offered free medical treatment to patients considered morally
      deserving but unable to afford medical care elsewhere. The role expected of
      Stewart was to means test patients in order to ensure that only those deemed
      "appropriate" received free medical treatment, and to establish the extent to
      which the hospital was being abused by those who could afford to contribute
      toward their medical care. While in office, Stewart continually reshaped the role
      of almoner. She fashioned the position into that of a medical social worker and
      undertook such duties as referring patients to other means of medical and
      charitable assistance, visiting patients' homes, and training almoners for
      positions at other voluntary hospitals. Through the examination of Mary Stewart's
      Almoners Report Book, this article considers the circumstances of her
      appointment, the role she performed, and the findings of her investigations. 

PMID- 22474099
TI  - Time as a dimension of medical law.
AB  - This paper considers the importance of temporal categories in medical law
      argumentation. Proceeding from a view of time as plural, rhetorical, and socially
      produced, it argues that decision making in areas such as the access of minors to
      contraception, abortion law, end of life care, and emergency caesarian sections
      can be usefully read as struggles over appropriate time frames. Judges,
      legislators, and commentators seek to establish the plausibility of a given legal
      development with reference to the common sense understanding of time which it
      embodies. Such understandings may be plausible because of their resonance with
      the diverse temporalities of the law itself. Alternatively, they may reproduce
      the temporal frames proper to medical science. Not only is time represented in
      medical law rhetoric, but deliberation in such cases is also subject to temporal
      pressures which may significantly affect their outcome. The paper concludes by
      considering the broader political stakes of intertemporal struggles in medical
      law.

PMID- 22474100
TI  - Minors' capacity to refuse treatment: a reply to Gilmore and Herring.
AB  - Re R and Re W allow a parent to consent to treatment a competent minor refuses,
      but the cases have not been tested post-Human Rights Act 1998. Gilmore and
      Herring offer a means by which they might be distinguished or sidelined. They
      interpret Gillick to say that in order to consent a minor need only have a full
      understanding of the particular treatment. They argue that the minors in Re R and
      Re W were refusing all treatment which requires a separate assessment of capacity
      an assessment which was not made. We fear that this distinction would not be
      workable in clinical practice and argue that their interpretation of Gillick is
      flawed. From a clinician's point of view, competence cannot always be judged in
      relation to a specific treatment, but instead must relate to the decision. We
      show that a decision can incorporate more than one treatment, and more than one
      decision might be made about one treatment. A minor's understanding of a specific
      treatment is not always sufficient to demonstrate competence to make a decision.
      The result is that whilst there might be situations when a parent and a minor
      both have the power to consent to a particular treatment, they will not share
      concurrent powers in relation to the same decision. Consequently, a challenge to
      Re R and Re W, if forthcoming, would need to take a different form. We emphasise
      the necessity to minimise the dichotomy between legal consent and how consent
      works in medical practice.

PMID- 22474102
TI  - Diego Rivera's Man at the Crossroads.

PMID- 22474103
TI  - Reduced dopamine receptor sensitivity as an intermediate phenotype in alcohol
      dependence and the role of the COMT Val158Met and DRD2 Taq1A genotypes.
AB  - CONTEXT: Alcohol dependence is a common neuropsychiatric disorder with high
      heritability. However, genetic association studies on alcohol dependence are
      often troubled by nonreplication. The use of intermediate phenotypes may help
      make clear the mode of action of various candidate genes and improve the
      reproducibility of genetic association studies. OBJECTIVE: To test central
      dopamine receptor sensitivity as an intermediate phenotype for alcohol
      dependence, specifically evaluating the hypothesis that the dopaminergic genes
      COMT Val158Met and DRD2 Taq1A affect dopamine receptor sensitivity. DESIGN: Case
      control pharmacogenetic challenge study. SETTING: Patients with alcohol
      dependence admitted for detoxification were compared with healthy control
      subjects matched for age and level of education. PARTICIPANTS: Patients (n = 110)
      were a consecutive sample, whereas controls (n = 99) were recruited through
      advertisements in regional newspapers. INTERVENTION: A dopamine challenge test
      was subcutaneously administered using the dopamine agonist apomorphine
      hydrochloride (0.005 mg/kg). MAIN OUTCOME MEASURES: Outcome measures were plasma
      growth hormone levels and results of a continuous performance task. RESULTS:
      Central dopamine receptor sensitivity is reduced in alcohol dependence, and this
      is modulated by dopaminergic genes. Specifically, DRD2 Taq1A genotype affected
      dopamine receptor sensitivity as measured by plasma growth hormone levels, and
      COMT Val158Met genotype affected dopamine receptor sensitivity as measured by
      performance on a continuous performance task. In a logistic regression analysis,
      reduced dopamine receptor sensitivity on both measures predicted alcohol
      dependence, without an additive effect of the COMT Val158Met and DRD2 Taq1A
      genotypes. CONCLUSIONS: COMT Val158Met and DRD2 Taq1A may affect the intermediate
      phenotype of central dopamine receptor sensitivity. COMT Val158Met and DRD2 Taq1A
      may confer their risk of alcohol dependence through reduced dopamine receptor
      sensitivity in the prefrontal cortex and hindbrain, respectively.

PMID- 22474104
TI  - Overlapping and segregating structural brain abnormalities in twins with
      schizophrenia or bipolar disorder.
AB  - CONTEXT: The nosologic dichotomy between schizophrenia and bipolar disorder (BD)
      as formulated by Kraepelin is currently being questioned, stimulated by the
      finding that schizophrenia and BD partly share a common genetic origin. Although
      both disorders are characterized by changes in brain structure, family studies
      suggest more segregating than overlapping neuroanatomical abnormalities in both
      disorders. OBJECTIVES: To investigate whether patients with schizophrenia and
      patients with BD display overlapping abnormalities in brain volumes and cortical
      thickness and whether these are caused by shared genetic or environmental
      influences. DESIGN: Magnetic resonance imaging findings of monozygotic (MZ) and
      dizygotic (DZ) twin pairs discordant for schizophrenia, twin pairs concordant and
      discordant for BD, and healthy twin pairs were compared using structural equation
      modeling. SETTING: The Netherlands Twin Register and University Medical Center
      Utrecht. PARTICIPANTS: A total of 310 individuals from 158 (152 complete and 6
      incomplete) twin pairs were included: 26 pairs discordant for schizophrenia (13
      MZ and 13 DZ), 49 pairs with BD (9 MZ and 4 DZ concordant; 14 MZ and 22 DZ
      discordant), and 83 healthy twin pairs (44 MZ and 39 DZ). MAIN OUTCOME MEASURES:
      Estimates of additive genetic and unique environmental associations between
      schizophrenia and BD with overlapping and nonoverlapping volumes and cortical
      thickness. RESULTS: Higher genetic liabilities for schizophrenia and BD were
      associated with smaller white matter volume, thinner right (and left)
      parahippocampus, thinner right orbitofrontal cortex, and thicker temporoparietal
      and left superior motor cortices; higher environmental liabilities were
      associated with thinner right medial occipital cortex. Genetic liability for
      schizophrenia was associated with thicker right parietal cortex; for BD, with
      larger intracranial volume. CONCLUSIONS: Brain structures reflect overlapping and
      segregating genetic liabilities for schizophrenia and BD. The overlapping smaller
      white matter volume and common areas of thinner cortex suggest that both
      disorders share genetic (neurodevelopmental) roots.

PMID- 22474105
TI  - Dorsolateral prefrontal cortex activation during emotional anticipation and
      neuropsychological performance in posttraumatic stress disorder.
AB  - CONTEXT: Posttraumatic stress disorder (PTSD) has been associated with executive
      or attentional dysfunction and problems in emotion processing. However, it is
      unclear whether these two domains of dysfunction are related to common or
      distinct neurophysiological substrates. OBJECTIVE: To examine the hypothesis that
      greater neuropsychological impairment in PTSD relates to greater disruption in
      prefrontal-subcortical networks during emotional anticipation. DESIGN: Case
      control, cross-sectional study. SETTING: General community and hospital and
      community psychiatric clinics. PARTICIPANTS: Volunteer sample of 37 women with
      PTSD related to intimate partner violence and 34 age-comparable healthy control
      women. MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging
      (fMRI) to examine neural responses during anticipation of negative and positive
      emotional images. The Clinician-Administered PTSD Scale was used to characterize
      PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition,
      Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference
      Test, and Wisconsin Card Sorting Test were used to characterize
      neuropsychological performance. RESULTS: Women with PTSD performed worse on
      complex visuomotor processing speed (Digit Symbol Test) and executive function
      (Color-Word Interference Inhibition/Switching subtest) measures compared with
      control subjects. Posttraumatic stress disorder was associated with greater
      anterior insula and attenuated lateral prefrontal cortex (PFC) activation during
      emotional anticipation. Greater dorsolateral PFC activation (anticipation of
      negative images minus anticipation of positive images) was associated with lower
      PTSD symptom severity and better visuomotor processing speed and executive
      functioning. Greater medial PFC and amygdala activation related to slower
      visuomotor processing speed. CONCLUSIONS: During emotional anticipation, women
      with PTSD show exaggerated activation in the anterior insula, a region important
      for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD
      patients during emotional anticipation may reflect engagement of cognitive
      control networks that are beneficial for emotional and cognitive functioning.
      Novel treatments could be aimed at strengthening the balance between cognitive
      control (dorsolateral PFC) and affective processing (medial PFC and amygdala)
      networks to improve overall functioning for PTSD patients.

PMID- 22474106
TI  - Severity of 12-month DSM-IV disorders in the National Comorbidity Survey
      Replication Adolescent Supplement.
AB  - CONTEXT: Estimates of DSM-IV disorder prevalence are high; stringent criteria to
      define need for services are desired. OBJECTIVE: To present US national data on
      the prevalence and sociodemographic correlates of 12-month serious emotional
      disturbance (SED), defined by the US Substance Abuse and Mental Health Services
      Administration, from the National Comorbidity Survey Replication Adolescent
      Supplement. DESIGN: The National Comorbidity Survey Replication Adolescent
      Supplement is a national survey of DSM-IV anxiety, mood, behavior, and substance
      disorders among US adolescents. SETTING: Dual-frame household and school samples
      of US adolescents. PARTICIPANTS: Total of 6483 pairs of adolescents aged 13 to 17
      (interviews) and parents (questionnaires). MAIN OUTCOME MEASURES: The DSM-IV
      disorders were 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. Serious emotional disturbance was operationalized as a DSM-IV/Composite
      International Diagnostic Interview disorder with a score of 50 or less on the
      Children's Global Assessment Scale (ie, moderate impairment in most areas of
      functioning or severe impairment in at least 1 area). Concordance of Composite
      International Diagnostic Interview SED diagnoses with blinded Schedule for
      Affective Disorders and Schizophrenia for School-Age Children diagnoses was good.
      RESULTS: The estimated prevalence of SED was 8.0%. Most SEDs were due to behavior
      (54.5%) or mood (31.4%) disorders. Although respondents with 3 or more disorders
      made up only 29.0% of those with 12-month DSM-IV/Composite International
      Diagnostic Interview disorders, they constituted 63.5% of SEDs. Predictive
      effects of high comorbidity were significantly greater than the product of their
      disorder-specific odds ratios and consistent across disorder types. Associations
      of sociodemographic variables with SED were generally nonsignificant after
      controlling for disorder type and number. CONCLUSIONS: The high estimated 12
      month prevalence of DSM-IV disorders among US adolescents is largely due to mild
      cases. The significant between-disorder differences in risk of SED and the
      significant effect of high comorbidity have important public health implications
      for targeting interventions.

PMID- 22474107
TI  - Use and abuse of alcohol and illicit drugs in US adolescents: results of the
      National Comorbidity Survey-Adolescent Supplement.
AB  - CONTEXT: Comprehensive descriptions of substance use and abuse trajectories have
      been lacking in nationally representative samples of adolescents. OBJECTIVE: To
      examine the prevalence, age at onset, and sociodemographic correlates of alcohol
      and illicit drug use and abuse among US adolescents. DESIGN: Cross-sectional
      survey of adolescents using a modified version of the Composite International
      Diagnostic Interview. SETTING: Combined household and school adolescent samples.
      PARTICIPANTS: Nationally representative sample of 10,123 adolescents aged 13 to
      18 years. MAIN OUTCOME MEASURES: Lifetime estimates of alcohol and illicit
      substance use and DSM-IV diagnoses of abuse, with or without dependence. RESULTS:
      By late adolescence, 78.2% of US adolescents had consumed alcohol, 47.1% had
      reached regular drinking levels defined by at least 12 drinks within a given
      year, and 15.1% met criteria for lifetime abuse. The opportunity to use illicit
      drugs was reported by 81.4% of the oldest adolescents, drug use by 42.5%, and
      drug abuse by 16.4%. The median age at onset was 14 years for alcohol abuse with
      or without dependence, 14 years for drug abuse with dependence, and 15 years for
      drug abuse without dependence. The associations observed by age, sex, and
      race/ethnicity often varied significantly by previous stage of use. CONCLUSIONS:
      Alcohol and drug use is common in US adolescents, and the findings of this study
      indicate that most cases of abuse have their initial onset in this important
      period of development. Prevention and treatment efforts would benefit from
      careful attention to the correlates and risk factors that are specific to the
      stage of substance use in adolescents.

PMID- 22474108
TI  - Sex differences in availability of beta2*-nicotinic acetylcholine receptors in
      recently abstinent tobacco smokers.
AB  - CONTEXT: Sex differences exist in the reinforcing effects of nicotine, smoking
      cessation rates, and response to nicotine therapies. Sex differences in
      availability of nicotinic acetylcholine receptors containing the beta(2) subunit
      (beta(2)*-nAChRs) may underlie differential nicotine and tobacco smoking effects
      and related behaviors in women vs men. OBJECTIVES: To examine beta(2)*-nAChR
      availability in male and female smokers vs nonsmokers and to determine
      associations among beta(2)*-nAChR availability, tobacco smoking characteristics,
      and female sex steroid hormone levels. DESIGN: Male (n = 26) and female (n = 28)
      tobacco smokers participated in an iodide 123-labeled 5-iodo-A-85380 ([(123)I]5
      IA) single-photon emission computed tomography (SPECT) imaging session at 7 to 9
      days of abstinence. Age-matched male (n = 26) and female (n = 30) nonsmokers
      participated in a [(123)I]5-IA SPECT imaging session. All participants completed
      a magnetic resonance imaging study. SETTING: Academic imaging center.
      PARTICIPANTS: Tobacco smokers (n = 54) and age- and sex-matched nonsmokers (n =
      56). MAIN OUTCOME MEASURE: The [(123)I]5-IA SPECT images were converted to
      equilibrium distribution volumes and were analyzed using regions of interest.
      RESULTS: The beta(2)*-nAChR availability was significantly higher in male smokers
      compared with male nonsmokers in striatum, cortex, and cerebellum, but female
      smokers did not have higher beta(2)*-nAChR availability than female nonsmokers in
      any region. In women, beta(2)*-nAChR availability in the cortex and cerebellum
      was negatively and significantly correlated with progesterone level on the SPECT
      imaging day. In female smokers on imaging day, the progesterone level was
      positively and significantly correlated with depressive symptoms, craving for a
      cigarette, and nicotine withdrawal. CONCLUSIONS: The regulatory effects of
      nicotine in the brain (ie, tobacco smoking-induced upregulation of beta(2)*
      nAChRs) seem to be distinctly different between men and women, and female sex
      steroid hormones likely have a role in this regulation. These findings suggest an
      underlying neurochemical mechanism for the reported behavioral sex differences.
      To treat female smokers more effectively, it is critical that nonnicotinic
      mediated medications should be explored.

PMID- 22474109
TI  - Hepatocarcinogenesis in FXR-/- mice mimics human HCC progression that operates
      through HNF1alpha regulation of FXR expression.
AB  - Farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4) is a
      member of nuclear hormone receptor superfamily, which plays essential roles in
      metabolism of bile acids, lipid, and glucose. We previously showed spontaneously
      hepatocarcinogenesis in aged FXR(-/-) mice, but its relevance to human
      hepatocellular carcinoma (HCC) is unclear. Here, we report a systematical
      analysis of hepatocarcinogenesis in FXR(-/-) mice and FXR expression in human
      liver cancer. In this study, liver tissues obtained from FXR(-/-) and wild-type
      mice at different ages were compared by microarray gene profiling, histological
      staining, chemical analysis, and quantitative real-time PCR. Primary hepatic
      stellate cells and primary hepatocytes isolated from FXR(-/-) and wild-type mice
      were also analyzed and compared. The results showed that the altered genes in
      FXR(-/-) livers were mainly related to metabolism, inflammation, and fibrosis,
      which suggest that hepatocarcinogenesis in FXR(-/-) mice recapitulated the
      progression of human liver cancer. Indeed, FXR expression in human HCC was down
      regulated compared with normal liver tissues. Furthermore, the proinflammatory
      cytokines, which were up-regulated in human HCC microenvironment, decreased FXR
      expression by inhibiting the transactivity of hepatic nuclear factor 1alpha on
      FXR gene promoter. Our study thereby demonstrates that the down-regulation of FXR
      has an important role in human hepatocarcinogenesis and FXR(-/-) mice provide a
      unique animal model for HCC study.

PMID- 22474110
TI  - Critical role of TRPC1-mediated Ca2+ entry in decidualization of human
      endometrial stromal cells.
AB  - Decidualization is an ovarian steroid-induced remodeling/differentiation process
      of uterus essential for embryo implantation and placentation. Here, we
      investigated the possible involvement of enhanced Ca2+ dynamics in the
      decidualization process in human endometrial stromal cells (hESC) in its
      connection with a recently emerging nonvoltage-gated Ca2+ entry channel
      superfamily, the transient receptor potential (TRP) protein. Combined application
      of 17beta-estradiol (E2) (10 nM) and progesterone (P4) (1 MUM) for 7-14 d
      resulted in morphological changes of hESC characteristic of decidualization (i.e.
      cell size increase), whereas sole application of E2 exerted little effects. A 7-
      to 14-d E2/P4 treatment greatly increased the expression level of decidualization
      markers IGF binding protein-1 (IGFBP-1) and prolactin and also up-regulated the
      expression of TRPC1, a canonical TRP subfamily member that has been implicated in
      store-operated Ca2+ influx (SOC) in other cell types. In parallel with this up
      regulation, SOC activity in hESC, the nuclear translocation of phosphorylated
      cAMP responsive element binding protein (p-CREB) and the expression of Forkhead
      box protein 01 were enhanced significantly. Small interfering RNA knockdown of
      TRPC1 counteracted the E2/P4-induced up-regulation of IGFBP-1 and prolactin and
      enhancement of SOC activity together with the inhibition of hESC size increase, p
      CREB nuclear translocation, and FOXO1 up-regulation. Coadministration of SOC
      inhibitors SK&F96365 or Gd3+ with E2/P4 also suppressed the up-regulation of
      IGFBP-1 and hESC size increase. Similar inhibitory effects were observed with
      extracellularly applied TRPC1 extracellular loop 3-directed antibody, which is
      known to bind a near-pore domain of TRPC1 channel and block its Ca2+ transporting
      activity. These results strongly suggest that up-regulation of TRPC1 protein and
      consequent enhancement of SOC-mediated Ca2+ influx may serve as a crucial step
      for the decidualization process of hESC probably via p-CREB-dependent
      transcriptional activity associated with FOXO1 activation.

PMID- 22474111
TI  - Impact of divorce on children: developmental considerations.
AB  - Although divorce can have significant negative impact on children, a variety of
      protective factors can increase the likelihood of long-term positive
      psychological adjustment. * Exposure to high levels of parental conflict is
      predictive of poor emotional adjustment by the child regardless of the parents'
      marital status. * Epidemiologic data reveal that custody and parenting
      arrangements are evolving, with more emphasis on joint custody and access to both
      parents by the child. * Pediatricians' knowledge of childhood development is
      essential in providing anticipatory guidance to parents throughout the divorce
      process and beyond.

PMID- 22474112
TI  - Cytomegalovirus infection.
AB  - Although commonly asymptomatic, congenital CMV infection is the leading cause of
      nonhereditary SNHL. Other sequelae that may be evident only after the neonatal
      period can include chorioretinitis, neurodevelopmental delay with mental or motor
      impairment, and microcephaly. (13) * Congenital CMV infection is confirmed by
      detection of the virus in urine, blood, or saliva within the first 3 weeks of
      life by culture or polymerase chain reaction. A positive test does not
      necessarily confirm symptomatic CMV disease or need for treatment. (13) *
      Postnatal CMV infections transmitted through human milk have been reported and
      may be clinically relevant in extremely premature infants; however, the risk
      benefit ratio of pasteurizing human milk for the prevention of postnatal CMV
      infection is unclear. * Ganciclovir, valganciclovir, foscarnet, cidofovir, and
      CMV hyperimmune globulin are effective in treating or preventing CMV infections
      in the immunocompromised host, but require close monitoring for associated
      toxicities. Treatment for congenital CMV is associated with significant toxicity
      and uncertain effectiveness. * Based on strong evidence, anticipatory guidance
      for congenital CMV infection should include hearing tests and neurodevelopmental
      assessments until school age. (3) In patients with symptomatic congenital CMV
      infection, lifelong ophthalmologic screening should be included. (4) * Based
      primarily on consensus, owing to lack of relevant clinical studies, it is not
      recommended to withhold human milk produced by CMV-seropositive mothers from
      healthy term infants. (5)(6) * Based on some research evidence, as well as
      consensus, treatment for congenital CMV is recommended only in symptomatic
      infants with central nervous system involvement. (9)

PMID- 22474113
TI  - Guillain-Barre syndrome.
AB  - * Based on strong research evidence, in countries where poliomyelitis has been
      eliminated, GBS is the most common cause of acquired paralysis in children. (9) *
      Based on strong research evidence, GBS describes a spectrum of disorders caused
      by an autoimmune reaction against peripheral nerve components, including the
      myelin sheath and the axon. (10)(11) * Based on strong research evidence, GBS
      usually is preceded by a bacterial or viral infection, less likely by vaccination
      in the 1 to 4 weeks before onset. The strongest relationship is with infection by
      C jejuni. (12)(13) * Based on strong research evidence, GBS in children most
      often presents with symmetrical ascending paralysis, diminished or absent
      reflexes, and often severe pain. Pain may lead to a delay in diagnosis. (2)
      (3)(9)(14) * Based on strong research evidence, the progressive phase peaks in 7
      to 14 days and can lead to various levels of weakness, from abnormal gait to
      total paralysis, cranial nerve weakness, pain, respiratory compromise, and
      autonomic instability. (2) * Based on some research evidence and consensus,
      children require hospitalization and often intensive care until their condition
      stabilizes because of significant risk of respiratory compromise and autonomic
      instability. (15) * Based on strong research evidence in adults and some research
      evidence in children, IVIG and plasma exchange hasten recovery from GBS in
      patients with impaired ability to ambulate. (4)(6) * Based primarily on
      consensus, IVIG is the treatment of choice in children with GBS. (6)(9)(15) *
      Based on strong research evidence, the prognosis for full functional recovery in
      childhood GBS is excellent. (2)(8)(9).

PMID- 22474114
TI  - Survival analysis.

PMID- 22474115
TI  - A 4-year-old male who has a persistent, severe headache.

PMID- 22474116
TI  - Index of suspicion * Case 1: Abdominal pain, fever, and cough in a 3-year-old
      boy. * Case 2: Emesis, irritability in 9-year-old boy who has autism. * Case 3:
      Skin lesions and pulmonary nodules in a 17-year-old boy.

PMID- 22474117
TI  - Anemia in infancy.

PMID- 22474118
TI  - Acetaminophen and Ibuprofen overdosage.

PMID- 22474119
TI  - Masturbation.

PMID- 22474120
TI  - Superficial fungal infections.
AB  - Tinea capitis, tinea corporis, and pityriasis versicolor are common superficial
      fungal infections in the pediatric population. * Tinea capitis is the most common
      dermatophyte infection worldwide. In North America, the cause is almost
      exclusively T tonsurans. Diagnosis of tinea capitis usually can be made by
      clinical features alone, especially when occipital or postauricular
      lymphadenopathy is present. Skin scrapings prepared with potassium hydroxide for
      microscopic examination, or a cotton swab for fungal culture, usually are
      diagnostic. * Treatment of tinea capitis requires systemic antifungal therapy.
      Terbinafine and griseofulvin are both effective against T tonsurans and are FDA
      approved for this indication in children. * Adjunctive topical therapy for the
      patient and household contacts decreases transmission of this infection. *
      Topical antifungal therapy usually is effective for tinea corporis and pityriasis
      versicolor. However, recurrences of pityriasis versicolor are common.

PMID- 22474121
TI  - MageComet--web application for harmonizing existing large-scale experiment
      descriptions.
AB  - MOTIVATION: Meta-analysis of large gene expression datasets obtained from public
      repositories requires consistently annotated data. Curation of such experiments,
      however, is an expert activity which involves repetitive manipulation of text.
      Existing tools for automated curation are few, which bottleneck the analysis
      pipeline. RESULTS: We present MageComet, a web application for biologists and
      annotators that facilitates the re-annotation of gene expression experiments in
      MAGE-TAB format. It incorporates data mining, automatic annotation, use of
      ontologies and data validation to improve the consistency and quality of
      experimental meta-data from the ArrayExpress Repository.

PMID- 22474122
TI  - CONTRA: copy number analysis for targeted resequencing.
AB  - MOTIVATION: In light of the increasing adoption of targeted resequencing (TR) as
      a cost-effective strategy to identify disease-causing variants, a robust method
      for copy number variation (CNV) analysis is needed to maximize the value of this
      promising technology. RESULTS: We present a method for CNV detection for TR data,
      including whole-exome capture data. Our method calls copy number gains and losses
      for each target region based on normalized depth of coverage. Our key strategies
      include the use of base-level log-ratios to remove GC-content bias, correction
      for an imbalanced library size effect on log-ratios, and the estimation of log
      ratio variations via binning and interpolation. Our methods are made available
      via CONTRA (COpy Number Targeted Resequencing Analysis), a software package that
      takes standard alignment formats (BAM/SAM) and outputs in variant call format
      (VCF4.0), for easy integration with other next-generation sequencing analysis
      packages. We assessed our methods using samples from seven different target
      enrichment assays, and evaluated our results using simulated data and real
      germline data with known CNV genotypes.

PMID- 22474123
TI  - Extending induced ROC methodology to the functional context.
AB  - The receiver operating characteristic (ROC) curve is the most widely used measure
      for evaluating the discriminatory performance of a continuous marker. Often,
      covariate information is also available and several regression methods have been
      proposed to incorporate covariate information in the ROC framework. Until now,
      these methods are only developed for the case where the covariate is univariate
      or multivariate. We extend ROC regression methodology for the case where the
      covariate is functional rather than univariate or multivariate. To this end,
      semiparametric- and nonparametric-induced ROC regression estimators are proposed.
      A simulation study is performed to assess the performance of the proposed
      estimators. The methods are applied to and motivated by a metabolic syndrome
      study in Galicia (NW Spain).

PMID- 22474124
TI  - Enhanced GLP-1- and sulfonylurea-induced insulin secretion in islets lacking
      leptin signaling.
AB  - We have previously reported that the absence of leptin signaling in beta-cells
      enhances glucose-stimulated insulin secretion and improves glucose tolerance in
      vivo. To investigate the relevance of beta-cell leptin signaling in the context
      of postprandial or therapeutic insulin secretion, we examined the cross talk
      between leptin and glucagon-like peptide (GLP)-1 and sulfonylurea actions. Single
      and size-matched islets isolated from control or pancreas-specific leptin
      receptor knockout (pancreas-ObR-KO) mice were treated either with GLP-1 or with
      glibenclamide. Leptin suppressed GLP-1-stimulated intracellular Ca(2+)
      concentrations ([Ca(2+)](i)) increase that paralleled the decrease in insulin
      secretion in controls. In contrast, and as expected, the ObR-KO islets were
      nonresponsive to leptin, and instead, showed a 2.8-fold greater GLP-1-stimulated
      [Ca(2+)](i) increase and a 1.7-fold greater insulin secretion. Phosphorylation of
      cAMP-responsive element binding protein was enhanced, and phosphodiesterase
      enzymatic activity was suppressed in MIN6 beta-cells with ObR knockdown compared
      with controls. The ObR-KO islets also showed significantly higher glibenclamide
      induced insulin secretion compared with control islets, whereas [Ca(2+)](i) was
      similar to the controls. These data support enhanced insulinotropic effects of
      glucose, GLP-1, and sulfonylureas in the islets lacking leptin signaling with
      potential therapeutic implications.

PMID- 22474125
TI  - Bile acids down-regulate caveolin-1 in esophageal epithelial cells through sterol
      responsive element-binding protein.
AB  - Bile acids are synthesized from cholesterol and are major risk factors for
      Barrett adenocarcinoma (BAC) of the esophagus. Caveolin-1 (Cav1), a scaffold
      protein of membrane caveolae, is transcriptionally regulated by cholesterol via
      sterol-responsive element-binding protein-1 (SREBP1). Cav1 protects squamous
      epithelia by controlling cell growth and stabilizing cell junctions and matrix
      adhesion. Cav1 is frequently down-regulated in human cancers; however, the
      molecular mechanisms that lead to this event are unknown. We show that the basal
      layer of the nonneoplastic human esophageal squamous epithelium expressed Cav1
      mainly at intercellular junctions. In contrast, Cav1 was lost in 95% of tissue
      specimens from BAC patients (n = 100). A strong cytoplasmic expression of Cav1
      correlated with poor survival in a small subgroup (n = 5) of BAC patients, and
      stable expression of an oncogenic Cav1 variant (Cav1-P132L) in the human BAC cell
      line OE19 promoted proliferation. Cav1 was also detectable in immortalized human
      squamous epithelial, Barrett esophagus (CPC), and squamous cell carcinoma cells
      (OE21), but was low in BAC cell lines (OE19, OE33). Mechanistically, bile acids
      down-regulated Cav1 expression by inhibition of the proteolytic cleavage of 125
      kDa pre-SREBP1 from the endoplasmic reticulum/Golgi apparatus and nuclear
      translocation of active 68-kDa SREBP1. This block in SREBP1's posttranslational
      processing impaired transcriptional activation of SREBP1 response elements in the
      proximal human Cav1 promoter. Cav1 was also down-regulated in esophagi from
      C57BL/6 mice on a diet enriched with 1% (wt/wt) chenodeoxycholic acid. Mice
      deficient for Cav1 or the nuclear bile acid receptor farnesoid X receptor showed
      hyperplasia and hyperkeratosis of the basal cell layer of esophageal epithelia,
      respectively. These data indicate that bile acid-mediated down-regulation of Cav1
      marks early changes in the squamous epithelium, which may contribute to onset of
      Barrett esophagus metaplasia and progression to BAC.

PMID- 22474134
TI  - Value of the student pharmacist to experiential practice sites: a review of the
      literature.
AB  - OBJECTIVE: To summarize the literature addressing clinical services provided by
      pharmacy students and the economic implications associated with those services.
      DATA SOURCES: A literature search was performed through MEDLINE and International
      Pharmaceutical Abstracts from their inception through December 2011. Search terms
      included pharmacy students, doctor of pharmacy students, clinical interventions,
      documentations, and medication histories. STUDY SELECTION AND DATA EXTRACTION:
      All research articles and abstracts published in English were included. Studies
      were excluded if they were not conducted in the US. Articles were reviewed and
      abstracted for number of interventions and proportion of total interventions
      performed by pharmacy students, type and duration of advanced practice
      experience, patient care location, time required for interventions, frequency of
      interventions that were accepted or implemented, and financial assessment of
      interventions when reported. DATA SYNTHESIS: A total of 29 fully published
      studies and 6 abstracts were identified. The majority of the studies evaluated
      the number of student recommendations made and the acceptance rate of those
      recommendations. On average, individual students made between 1.2 and 16
      recommendations to prescribers per week. The acceptance rate ranged from 32% to
      98%. In addition to recommendations, students performed intravenous to oral dose
      conversions and obtained medication histories. All of the studies that assessed
      the economic impact of student pharmacist involvement reported a cost savings or
      cost avoidance associated with having pharmacy students at the institution.
      CONCLUSIONS: Pharmacy students provide many recommendations with high acceptance
      rates. During their pharmacy practice experiences, students generally confer
      economic and clinical benefits that may exceed the costs associated with their
      supervision and training.

PMID- 22474126
TI  - Autotaxin and its product lysophosphatidic acid suppress brown adipose
      differentiation and promote diet-induced obesity in mice.
AB  - Brown adipose tissue is a thermogenic organ that dissipates stored energy as heat
      to maintain body temperature. This process may also provide protection from
      development of diet-induced obesity. We report that the bioactive lipid mediator
      lysophosphatidic acid (LPA) markedly decreases differentiation of cultured
      primary brown adipocyte precursors, whereas potent selective inhibitors of the
      LPA-generating enzyme autotaxin (ATX) promote differentiation. Transgenic mice
      overexpressing ATX exhibit reduced expression of brown adipose tissue-related
      genes in peripheral white adipose tissue and accumulate significantly more fat
      than wild-type controls when fed a high-fat diet. Our results indicate that ATX
      and its product LPA are physiologically relevant negative regulators of brown fat
      adipogenesis and are consistent with a model in which a decrease in mature
      peripheral brown adipose tissue results in increased susceptibility to diet
      induced obesity in mice.

PMID- 22474127
TI  - Peroxisome proliferator-activated receptor gamma decouples fatty acid uptake from
      lipid inhibition of insulin signaling in skeletal muscle.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed at low
      levels in skeletal muscle, where it protects against adiposity and insulin
      resistance via unclear mechanisms. To test the hypothesis that PPARgamma directly
      modulates skeletal muscle metabolism, we created two models that isolate direct
      PPARgamma actions on skeletal myocytes. PPARgamma was overexpressed in murine
      myotubes by adenotransfection and in mouse skeletal muscle by plasmid
      electroporation. In cultured myotubes, PPARgamma action increased fatty acid
      uptake and incorporation into myocellular lipids, dependent upon a 154 +/- 20
      fold up-regulation of CD36 expression. PPARgamma overexpression more than doubled
      insulin-stimulated thymoma viral proto-oncogene (AKT) phosphorylation during low
      lipid availability. Furthermore, in myotubes exposed to palmitate levels that
      inhibit insulin signaling, PPARgamma overexpression increased insulin-stimulated
      AKT phosphorylation and glycogen synthesis over 3-fold despite simultaneously
      increasing myocellular palmitate uptake. The insulin signaling enhancement was
      associated with an increase in activating phosphorylation of phosphoinositide
      dependent protein kinase 1 and a normalized expression of palmitate-induced genes
      that antagonize AKT phosphorylation. In vivo, PPARgamma overexpression more than
      doubled insulin-dependent AKT phosphorylation in lipid-treated mice but did not
      augment insulin-stimulated glucose uptake. We conclude that direct PPARgamma
      action promotes myocellular storage of energy by increasing fatty acid uptake and
      esterification while simultaneously enhancing insulin signaling and glycogen
      formation. However, direct PPARgamma action in skeletal muscle is not sufficient
      to account for the hypoglycemic actions of PPARgamma agonists during
      lipotoxicity.

PMID- 22474135
TI  - Adjusting eptifibatide doses for renal impairment: a model of dosing agreement
      among various methods of estimating creatinine clearance.
AB  - BACKGROUND: Because of the renal elimination and increased risk for bleeding
      events at supratherapeutic doses of eptifibatide, the manufacturer recommends
      dosing adjustment in patients with renal dysfunction. Methods commonly used to
      estimate renal dysfunction in hospital settings may be inconsistent with those
      studied and recommended by the manufacturer. OBJECTIVE: To compare hypothetical
      renal dosing adjustments of eptifibatide using both the recommended method and
      several other commonly used formulas for estimating kidney function. METHODS:
      Sex, age, weight, height, serum creatinine, and estimated glomerular filtration
      rate (eGFR) were obtained retrospectively from the records of patients who
      received eptifibatide during a 12-month period. Renal dosing decisions were
      determined for each patient based on creatinine clearance (CrCl) estimates via
      the Cockcroft-Gault formula (CG) with actual body weight (ABW), ideal body weight
      (IBW) or adjusted weight (ADJW), and eGFR from the Modification of Diet in Renal
      Disease formula. Percent agreement and Cohen kappa were calculated comparing
      dosing decisions for each formula to the standard CG-ABW. RESULTS: In this
      analysis of 179 patients, percent agreement as compared to CG-ABW varied (CG-IBW:
      90.50%, CG-ADJW: 95.53%, and eGFR: 93.30%). All kappa coefficients were
      categorized as good. In the 20% of patients receiving an adjusted dose by any of
      the methods, 68.6% could have received a dose different from that determined
      using the CG-ABW formula. CONCLUSIONS: In the patients with renal impairment
      (CrCl <50 mL/min) in this study, two thirds would have received an unnecessary
      50% dose adjustment discordant from the manufacturer's recommendation. Because
      failure to adjust eptifibatide doses in patients with renal impairment has led to
      increased bleeding events, practitioners may be inclined to err on the side of
      caution. However, studies have shown that suboptimal doses of eptifibatide lead
      to suboptimal outcomes. Therefore, correct dosing of eptifibatide is important to
      both patient safety and efficacy.

PMID- 22474136
TI  - Oral antidiabetic drugs and regression from prediabetes to normoglycemia: a meta
      analysis.
AB  - BACKGROUND: Impaired glucose tolerance, impaired fasting glucose, and elevated
      hemoglobin A(1c) are intermediate stages, considered prediabetes, a precursor to
      overt type 2 diabetes mellitus. Prediabetes is associated with increased risk for
      cardiovascular disease, independent of diabetes development. Data have shown that
      various oral antidiabetic drugs can help people regress from prediabetes to
      normoglycemia. OBJECTIVE: To evaluate the efficacy of oral antidiabetic drugs in
      promoting regression from prediabetes to normoglycemia. METHODS: MEDLINE (1950
      November 2011), EMBASE (1990-November 2011), and Cochrane Central Register of
      Controlled Trials (indexed September 2011) were systematically searched. A manual
      search of references from reports of clinical trials and review articles was
      performed to identify additional relevant studies. Randomized controlled trials
      12 weeks or more in duration evaluating any of the oral antidiabetic drugs and
      studying regression from prediabetes to normoglycemia were included. A random
      effects model was used to calculate pooled odds ratios with 95% confidence
      intervals. RESULTS: Thirteen studies (N = 11,600 participants) were included in
      the meta-analysis. Use of oral antidiabetic drugs in prediabetic patients was
      shown to double the odds of achieving normoglycemia compared to controls (OR
      2.03, 95% CI 1.54 to 2.67). When individual classes of oral antidiabetic drugs
      were evaluated, use of thiazolidinediones (OR 2.33, 95% CI 1.93 to 2.81) and
      alpha-glucosidase inhibitors (OR 2.02, 95% CI 1.26 to 3.24) was associated with
      significantly increased odds. However, biguanides (OR 2.04) and sulfonylureas (OR
      1.84) failed to reach statistical significance (p = 0.06 and p = 0.39,
      respectively). CONCLUSIONS: In patients with prediabetes, oral antidiabetic drugs
      were associated with increased odds of regression to normoglycemia versus
      placebo/control. Only thiazolidinediones and alpha-glucosidase inhibitors
      provided a statistically significant increase in odds of regressing to
      normoglycemia.

PMID- 22474137
TI  - Is statin-associated cognitive impairment clinically relevant? A narrative review
      and clinical recommendations.
AB  - OBJECTIVE: To explore the impact of statin use on cognition. DATA SOURCES: A
      literature search was performed using MEDLINE (1950-November 2011), EMBASE (1980
      November 2011), and the Cochrane Library (1960-November 2011) using the search
      terms "cognition/drug effects," "delirium, dementia, amnestic, cognitive
      disorders/chemically induced," "memory disorders/chemically induced,"
      "hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects," and
      "hydroxymethylglutaryl-CoA reductase inhibitors." A bibliographic search on
      included references was also conducted. STUDY SELECTION AND DATA EXTRACTION:
      Studies were included for analysis if they were conducted in humans and examined
      the impact of statin use on cognition as either a primary or secondary endpoint;
      case reports and case series were also included for analysis. DATA SYNTHESIS:
      Reports of statin-associated cognitive impairment were found primarily in
      observational studies (eg, case reports/series). One randomized controlled trial
      demonstrated that simvastatin impaired some measures of cognition compared to
      placebo. Conversely, in the majority of randomized controlled trials and
      observational studies, statins were found to have either a neutral or beneficial
      effect on cognition. Preliminary data suggest that statins that are less
      lipophilic (ie, pravastatin and rosuvastatin) may be less likely to contribute to
      cognitive impairment due to limited penetration across the blood-brain barrier.
      These drugs would be a logical alternative in cases where cognitive impairment
      secondary to another statin is suspected. CONCLUSIONS: Despite several reports of
      statin-associated cognitive impairment, this adverse effect remains a rare
      occurrence among the totality of the literature. If statin-associated cognitive
      impairment is suspected, a trial discontinuation can reveal a temporal
      relationship. Switching from lipophilic to hydrophilic statins may resolve
      cognitive impairment. The vascular benefits and putative cognitive benefits
      outweigh the risk of cognitive impairment associated with statin use; therefore,
      the current evidence does not support changing practice with respect to statin
      use, given this adverse effect.

PMID- 22474138
TI  - Probable celecoxib-induced hepatorenal syndrome.

PMID- 22474139
TI  - Phenomenology as a resource for patients.
AB  - Patient support tools have drawn on a variety of disciplines, including
      psychotherapy, social psychology, and social care. One discipline that has not so
      far been used to support patients is philosophy. This paper proposes that a
      particular philosophical approach, phenomenology, could prove useful for
      patients, giving them tools to reflect on and expand their understanding of their
      illness. I present a framework for a resource that could help patients to
      philosophically examine their illness, its impact on their life, and its meaning.
      I explain the need for such a resource, provide philosophical grounding for it,
      and outline the epistemic and existential gains philosophy offers. Illness often
      begins as an intrusion on one's life but with time becomes a way of being. I
      argue that this transition impacts on core human features such as the experience
      of space and time, human abilities, and adaptability. It therefore requires
      philosophical analysis and response. The paper uses ideas from Husserl and
      Merleau-Ponty to present such a response in the form of a phenomenological
      toolkit for patients. The toolkit includes viewing illness as a form of
      phenomenological reduction, thematizing illness, and examining illness as
      altering the ill person's being in the world. I suggest that this toolkit could
      be offered to patients as a workshop, using phenomenological concepts, texts, and
      film clips to reflect on illness. I conclude by arguing that examining illness as
      a limit case of embodied existence deepens our understanding of phenomenology.

PMID- 22474140
TI  - Varieties of temporal experience in depression.
AB  - People with depression often report alterations in their experience of time, a
      common complaint being that time has slowed down or stopped. In this paper, I
      argue that depression can involve a range of qualitatively different changes in
      the structure of temporal experience, some of which I proceed to describe. In
      addition, I suggest that current diagnostic categories such as "major depression"
      are insensitive to the differences between these changes. I conclude by briefly
      considering whether the kinds of temporal experience associated with depression
      are specific to depression.

PMID- 22474141
TI  - Organ transplantation and personal identity: how does loss and change of organs
      affect the self?
AB  - In this paper, changes in identity and selfhood experienced through organ
      transplantation are analyzed from a phenomenological point of view. The chief
      examples are heart and face transplants. Similarities and differences between the
      examples are fleshed out by way of identifying three layers of selfhood in which
      the procedures have effects: embodied selfhood, self-reflection, and social
      narrative identity. Organ transplantation is tied to processes of alienation in
      the three layers of selfhood, first and foremost a bodily alienation experienced
      through illness or injury and in going through and recovering from the operation.
      However, in cases in which the organ in question is taken to harbor the identity
      of another person, because of its symbolic qualities (the heart) or its
      expressive qualities (the face), the alienation process may also involve the
      otherness of another person making itself, at least imaginatively, known.

PMID- 22474142
TI  - The complex relationship between ischemic heart disease and COPD exacerbations.

PMID- 22474143
TI  - Promoting tobacco to women of reproductive age harms fetuses.

PMID- 22474144
TI  - Portopulmonary hypertension: light at the end of the tunnel?

PMID- 22474145
TI  - Point: should pleural manometry be performed routinely during thoracentesis? Yes.

PMID- 22474146
TI  - Counterpoint: should pleural manometry be performed routinely during
      thoracentesis? No.

PMID- 22474147
TI  - Defective phagocytosis in airways disease.
AB  - Maintaining an airway clear of inhaled particles, pathogens, and cellular debris
      is paramount for lung homeostasis. In healthy individuals, the phagocytes of the
      innate immune system act as sentinels to patrol the airway and ensure sterility.
      However, in airways diseases, including asthma, COPD, and cystic fibrosis, there
      is a propensity for bacterial colonization that may contribute to disease
      worsening. Evidence suggests that this may be due to dysfunctional phagocytosis.
      In patients with COPD, phagocytosis of several bacterial species and removal of
      apoptotic cells (efferocytosis) by alveolar macrophages are significantly
      reduced; however, these cells can remove inert beads normally. Attenuated
      phagocytosis is also apparent in monocyte-derived macrophages from the same
      patients, suggesting an inherent defect in these cells. Reduced expression of
      cell surface recognition receptors has been suggested as one mechanism for these
      observations; however, the literature is currently contradictory and requires
      further clarification. In cystic fibrosis, a similar defect is also observed in
      both airway neutrophils and macrophages, leading to ineffective bacterial uptake
      and subsequent killing. In asthma and other airways diseases, there are also
      reports of defective phagocytosis of bacterial pathogens, although the relevance
      to disease pathophysiology is not understood. Oxidative stress is emerging as a
      common mechanism that may be altering both macrophage and neutrophil functions
      that can be reversed by various antioxidant strategies. The identification of
      this and other mechanisms underlying phagocyte dysfunction may present novel
      therapeutic opportunities for the treatment of many of these intractable diseases
      and improve patient morbidity and mortality.

PMID- 22474148
TI  - Role of procalcitonin in managing adult patients with respiratory tract
      infections.
AB  - Respiratory infections remain the most common reason why patients seek medical
      care in ambulatory and hospital settings, and they are the most frequent
      precursor of sepsis. In light of the limitations of clinical signs and symptoms
      and traditional microbiologic diagnostics for respiratory infections, blood
      biomarkers that correlate with the presence and extent of bacterial infections
      may provide additional useful information to improve diagnostic and prognostic
      efforts and help with therapeutic decisions in individual patients. A growing
      body of evidence supports the use of procalcitonin (PCT) to differentiate
      bacterial from viral respiratory diagnoses, to help risk stratify patients, and
      to guide antibiotic therapy decisions about initial need for, and optimal
      duration of, therapy. Although still relatively new on the clinical frontier, a
      series of randomized controlled trials have evaluated PCT protocols for
      antibiotic-related decision making and have included patients from different
      clinical settings and with different severities of respiratory infection. In
      these trials, initial PCT levels were effective in guiding decisions about the
      initiation of antibiotic therapy in lower-acuity patients, and subsequent
      measurements were effective for guiding duration of therapy in higher-acuity
      patients, without apparent harmful effects. Recent European respiratory infection
      guidelines now also recognize this concept. As with any other laboratory test,
      PCT should not be used on a stand-alone basis. Rather, it must be integrated into
      clinical protocols, together with clinical, microbiologic data and with results
      from clinical risk scores. The aim of this review is to summarize recent evidence
      about the usefulness of PCT in patients with lower respiratory tract infections
      and to discuss the potential benefits and limitations of this marker when used
      for clinical decision making.

PMID- 22474149
TI  - Legal fundamentals of surrogate decision making.
AB  - The four previous articles in this series have traced the history of patient
      autonomy and have identified its ethical and legal foundations. Patient autonomy
      is highly valued in the United States to the extent that the patient does not
      lose the right of self-determination when he or she loses the capacity to make
      health-care decisions for him or herself. The law has devised several tools to
      promote "prospective autonomy." One mechanism is the instructional advance
      directive or living will. But most of us do not write such directives. Another
      mechanism is the proxy directive or durable power of attorney for health care,
      designating another person, a surrogate, to direct the course of our medical
      treatment upon our incapacity. But most of us do not do that either. Therefore,
      the most common mechanism by which our prospective autonomy is protected and
      promoted is through the informal selection of surrogates based on statutory
      priority lists. These "default" surrogates are the most numerous type of
      surrogate. This article explains the importance and legal fundamentals of
      surrogate decision making. It first describes five basic types of surrogates. The
      article then looks at the role of these surrogates and how they are supposed to
      make decisions on the patient's behalf. Unfortunately, surrogate performance is
      often mediocre or poor. There are significant and persistent obstacles to good
      surrogate decision making. After explaining these problems, the article concludes
      by identifying several solutions.

PMID- 22474150
TI  - CPR and postarrest care: overview, documentation, and databases.
AB  - It is estimated that 350,000 people suffer a cardiac arrest each year in the
      United States, with one-half occurring out-of-hospital and the other half in
      hospital. Overall survival is < 10% and has not changed significantly for
      decades. CPR is the umbrella term for attempts to restore organized cardiac
      contractility and functional blood flow. Physicians have studied resuscitation
      techniques for millennia. In 1964, Peter Safar published the first ABCs of Heart
      Lung Resuscitation, which included: (1) first aid, (2) start spontaneous
      circulation, and (3) support recovery. Many of these principles were incorporated
      into the first official CPR guidelines developed by the American Heart
      Association in 1966. These guidelines have been updated periodically since then,
      with the most recent iteration developed in November 2010. Fundamental
      principles, such as early defibrillation, chest compressions performed at the
      appropriate rate and depth, and delivery of postarrest care, are affirmed in the
      recent guidelines update. In addition, a greater emphasis has been placed on
      quality of CPR, with the need to minimize interruptions, the reordering of CPR
      priorities to place chest compressions before ventilations, and the need for
      comprehensive postarrest care that includes both targeted temperature and
      hemodynamic management. Whether a cardiac arrest occurs out-of-hospital or in
      hospital, the basic approach to CPR and postarrest care is identical.
      Documentation should be performed in a standardized fashion, using a consensus
      set of data elements known as the Utstein format, and can contribute to quality
      improvement, research, and billing efforts.

PMID- 22474151
TI  - Fractured indwelling pleural catheters.
AB  - Indwelling pleural catheters (IPCs) are increasingly used in the management of
      malignant pleural effusions. IPCs are designed to be secured in situ
      indefinitely; however, in selected patients, IPCs can be removed when drainage
      ceases. This case series reports complications of removal of IPCs that resulted
      in fractured catheters or necessitated deliberate severing of the catheters. From
      the combined data of two pleural centers, 61 of 170 IPCs inserted (35.9%) were
      removed. In six cases (9.8%), the removals were complicated, leading to fracture
      or iatrogenic severing of the IPC. Although four patients had catheter fragments
      retained within the pleural space, none developed any complications (eg, pain or
      infection) (median follow-up, 459 days; range, 113-1,119 days), despite two
      patients undergoing subsequent chemotherapy. Clinicians should be aware that IPC
      removal can be problematic, but retained fragments are safe, and aggressive
      retrieval is unnecessary.

PMID- 22474152
TI  - A pleural effusion of multiple causes.
AB  - Multiple medical disorders can lead to the development of pleural effusions. Most
      effusions are given a single diagnosis in clinical practice. However, the cause
      of the effusion can change during the disease course, and concomitant yet
      distinct causes are often underrecognized. We highlight this point by reporting a
      complex case of recurrent pleural effusions with different predominant causes
      during the disease course. Five causes for the pleural effusion were diagnosed,
      namely malignant pleural effusion, empyema, chylothorax, transudative pleural
      effusion secondary to hypoalbuminemia, and esophagopleural fistula. This case
      serves as a reminder to clinicians that recurrent pleural effusion, even within
      the same pleural space, can arise from different causes and, whenever clinically
      appropriate, reinvestigation of the pleural effusion may be needed.

PMID- 22474153
TI  - Pneumothorax in the critically ill patient.
AB  - Pneumothorax in critically ill patients remains a common problem in the ICU,
      occurring in 4% to 15% of patients. Pneumothorax should be considered a medical
      emergency and requires a high index of suspicion, prompt recognition, and
      intervention. The diagnosis of pneumothorax in the critically ill patient can be
      made by physical examination findings or radiographic studies including chest
      radiographs, ultrasonography, or CT scanning. Ultrasonography is emerging as the
      diagnostic procedure of choice for the diagnosis and management guidance and
      management of pneumothoraces, if expertise is available. Pneumothoraces in
      unstable, critically ill patients or in those on mechanical ventilation should be
      managed with tube thoracostomy. If there is suspicion for tension pneumothorax,
      immediate decompression and drainage should be performed. With widespread use of
      CT scanning, there have been more occult pneumothoraces diagnosed, and the most
      recent literature suggests that drainage is preferred. In patients with a
      persistent air leak or failure of the lung to expand, current guidelines suggest
      that an early thoracic surgical consultation be requested within 3 to 5 days.

PMID- 22474154
TI  - A 74-year-old woman with subacute dyspnea, profound hypoxemia, normal lung
      images, and refractory cardiopulmonary collapse.

PMID- 22474155
TI  - An unexpected consequence of electronic cigarette use.

PMID- 22474156
TI  - A better way to assess bronchoreversibility.

PMID- 22474157
TI  - Secondhand smoke exposure effect on elastin degradation markers: which factors
      should be taken into account?

PMID- 22474158
TI  - Risk of teratoma formation after transplantation of induced pluripotent stem
      cells.

PMID- 22474159
TI  - COPD and GOLD stage I.

PMID- 22474160
TI  - Contemporary aminophylline use for status asthmaticus in pediatric ICUs.

PMID- 22474161
TI  - What is the Pulmonary Rehabilitation Adapted Index of Self-Efficacy tool actually
      measuring?

PMID- 22474163
TI  - The language of goals of care: framing preferences at the end of life.

PMID- 22474162
TI  - Important antiretroviral drug interactions with benzodiazepines used for sedation
      during bronchoscopy.

PMID- 22474164
TI  - The value of chest ultrasonography in diagnosing pneumothorax in patients with
      trauma.

PMID- 22474166
TI  - Genome-wide analyses of recombination suggest that Giardia intestinalis
      assemblages represent different species.
AB  - Giardia intestinalis is a major cause of waterborne enteric disease in humans.
      The species is divided into eight assemblages suggested to represent separate
      Giardia species based on host specificities and the genetic divergence of marker
      genes. We have investigated whether genome-wide recombination occurs between
      assemblages using the three available G. intestinalis genomes. First, the
      relative nonsynonymous substitution rates of the homologs were compared for 4,009
      positional homologs. The vast majority of these comparisons indicate genetic
      isolation without interassemblage recombinations. Only a region of 6 kbp suggests
      genetic exchange between assemblages A and E, followed by gene conversion events.
      Second, recombination-detecting software fails to identify within-gene
      recombination between the different assemblages for most of the homologs. Our
      results indicate very low frequency of recombination between the syntenic core
      genes, suggesting that G. intestinalis assemblages are genetically isolated
      lineages and thus should be viewed as separated Giardia species.

PMID- 22474167
TI  - Conflicts of interest in medicine and science.

PMID- 22474168
TI  - Adenosine A2A and beta-2 adrenergic receptor agonists: novel selective and
      synergistic multiple myeloma targets discovered through systematic combination
      screening.
AB  - The use of combination drug regimens has dramatically improved the clinical
      outcome for patients with multiple myeloma. However, to date, combination
      treatments have been limited to approved drugs and a small number of emerging
      agents. Using a systematic approach to identify synergistic drug combinations,
      combination high-throughput screening (cHTS) technology, adenosine A2A and beta-2
      adrenergic receptor (beta2AR) agonists were shown to be highly synergistic,
      selective, and novel agents that enhance glucocorticoid activity in B-cell
      malignancies. Unexpectedly, A2A and beta2AR agonists also synergize with
      melphalan, lenalidomide, bortezomib, and doxorubicin. An analysis of agonists, in
      combination with dexamethasone or melphalan in 83 cell lines, reveals substantial
      activity in multiple myeloma and diffuse large B-cell lymphoma cell lines.
      Combination effects are also observed with dexamethasone as well as bortezomib,
      using multiple myeloma patient samples and mouse multiple myeloma xenograft
      assays. Our results provide compelling evidence in support of development of A2A
      and beta2AR agonists for use in multi-drug combination therapy for multiple
      myeloma. Furthermore, use of cHTS for the discovery and evaluation of new targets
      and combination therapies has the potential to improve cancer treatment paradigms
      and patient outcomes.

PMID- 22474169
TI  - Fyn inhibition by cycloalkane-fused 1,2-dithiole-3-thiones enhances antioxidant
      capacity and protects mitochondria from oxidative injury.
AB  - Fyn kinase has emerged as a regulator of diverse pathological processes. However,
      therapeutic Fyn inhibitors are not available. This study investigated the
      potential of a series of cycloalkane-fused dithiolethiones (CDTs) or other
      congeners to increase antioxidant capacity in association with Fyn inhibition, as
      well as the molecular basis for this effect. Treatment of HepG2 cells with each
      agent protected the mitochondria from oxidative injury elicited by arachidonic
      acid and iron, which increased cell viability; 4,5,6,7-tetrahydrobenzo-1,2
      dithiole-3-thione (SNU1A) and 5,6-dihydro-4H-cyclopenta-1,2-dithiole-3-thione
      (SNU2A) were the most effective, whereas 5-methyl-1,2-dithiole-3-thione (SNU3A)
      was less active. 5-(Quinolin-2-yl)-1,2-dithiole-3-thione (SNU3E) had a minimal
      effect. SNU1A treatment decreased mitochondrial superoxide production and enabled
      cells to restore mitochondrial membrane permeability. Oxidative injury caused by
      arachidonic acid and iron enhanced Fyn phosphorylation at a tyrosine residue,
      which was decreased by SNU1A treatment. 2,3-Dihydro-N,N-dimethyl-2-oxo-3
      [(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1H-indole-5-sulfonamide (SU6656), a
      known Fyn inhibitor, had a similar effect. Fyn inhibition contributed to
      protecting mitochondria from injury through AMP-activated protein kinase (AMPK),
      as supported by reversal of this effect with Fyn overexpression. Consistently,
      Fyn overexpression attenuated AMPK activation by SNU1A, which strengthens the
      inhibitory role of Fyn in AMPK activity. CDTs had antioxidant effects, as shown
      by increases in GSH contents and inhibition of H(2)O(2) production. They also had
      the ability to activate nuclear factor E2-related factor 2 (Nrf2), a key
      antioxidant transcription factor. Fyn overexpression decreased the Nrf2
      activation induced by SNU1A. Our results demonstrate that CDTs exert
      cytoprotective effects by protecting mitochondria and increasing the cellular
      antioxidant capacity, which may result not only from Fyn inhibition leading to
      AMPK activation but also from Nrf2 activation.

PMID- 22474170
TI  - Renal stones and calcifications in patients with primary hyperparathyroidism:
      associations with biochemical variables.
AB  - OBJECTIVE: To study the prevalence of renal stones and nephrocalcinosis in
      patients with primary hyperparathyroidism (PHPT) and to appraise biochemical
      variables as risk factors for developing renal calcifications. DESIGN: Cross
      sectional. MATERIALS AND METHODS: All patients (n=177) undergoing diagnostic
      evaluation and surgery for PHPT at Aarhus University Hospital between 2007 and
      2009. All patients underwent routine spiral CT scans of the abdomen to determine
      the presence or absence of renal calcifications. RESULTS: A total of 45 patients
      (25.4%, 95% confidence intervals: 19.0-31.4%) had renal stones (15.3%) and/or
      renal calcifications (10.2%) on the CT scans. Compared with those without
      calcification (n=132), the group with calcification had a significantly lower
      plasma creatinine level (67.0+/-25.1 vs 74.6+/-17.5 MUmol/l, 2P=0.03). Moreover,
      CaE was higher in PHPT patients with renal calcification than in PHPT patients
      without (0.91+/-0.28 vs 0.74+/-0.40 mmol/mmol, 2P=0.02). The other measured or
      derived biochemical variables were similar in the two groups. No biochemical
      variable was predictive for renal calcifications in a multiple regression
      analysis. CONCLUSION: We found a high prevalence of renal calcifications among
      PHPT patients but no deterioration of renal function. The occurrence of
      calcifications was related to low plasma creatinine and a high urine
      calcium/creatinine ratio. However, biochemical markers in general were poor
      predictors for the risk of renal stones or nephrocalcinosis indicating that
      routine image diagnostics may be needed for the identification of these
      complications in order to establish indication for surgery and ensure proper
      treatment.

PMID- 22474171
TI  - Testosterone production during puberty in two 46,XY patients with disorders of
      sex development and novel NR5A1 (SF-1) mutations.
AB  - BACKGROUND: Steroidogenic factor 1 (SF-1, NR5A1) is a key transcriptional
      regulator of many genes involved in the hypothalamic-pituitary-gonadal axis and
      mutations in NR5A1 can result in 46,XY disorders of sex development (DSD).
      Patients with this condition typically present with ambiguous genitalia, partial
      gonadal dysgenesis, and absent/rudimentary Mullerian structures. In these cases,
      testosterone is usually low in early infancy, indicating significantly impaired
      androgen synthesis. Further, Sertoli cell dysfunction is seen (low inhibin B,
      anti-Mullerian hormone). However, gonadal function at puberty in patients with
      NR5A1 mutations is unknown. SUBJECTS AND METHODS: Clinical assessment, endocrine
      evaluation, and genetic analysis were performed in one female and one male with
      46,XY DSD who showed spontaneous virilization during puberty. The female patient
      presented at adolescence with clitoral hypertrophy, whereas the male patient
      presented at birth with severe hypospadias and entered puberty spontaneously.
      Molecular analysis of NR5A1 was performed followed by in vitro functional
      analysis of the two novel mutations detected. RESULTS: Testosterone levels were
      normal during puberty in both patients. Analysis of NR5A1 revealed two novel
      heterozygous missense mutations in the ligand-binding domain of SF-1 (patient 1:
      p.L376F; patient 2: p.G328V). The mutant proteins showed reduced transactivation
      of the CYP11A promoter in vitro. CONCLUSION: Patients with 46,XY DSD and NR5A1
      mutations can produce sufficient testosterone for spontaneous virilization during
      puberty. Phenotypic females (46,XY) with NR5A1 mutations can present with
      clitoromegaly at puberty, a phenotype similar to other partial defects of
      androgen synthesis or action. Testosterone production in 46,XY males with NR5A1
      mutations can be sufficient for virilization at puberty. As progressive gonadal
      dysgenesis is likely, gonadal function should be monitored in adolescence and
      adulthood, and early sperm cryopreservation considered in male patients if
      possible.

PMID- 22474172
TI  - The SLCO1A2 gene, encoding human organic anion-transporting polypeptide 1A2, is
      transactivated by the vitamin D receptor.
AB  - Organic anion-transporting polypeptide 1A2 (OATP1A2) (gene symbol, SLCO1A2)
      mediates cellular uptake of a wide range of endogenous substrates, as well as
      drugs and xenobiotics. OATP1A2 is expressed in several tissues, including apical
      membranes of small intestinal epithelial cells. Given its role in intestinal drug
      absorption, a detailed analysis of the mechanisms that regulate SLCO1A2 gene
      expression is potentially of great pharmacological relevance. We show here that
      treatment of human intestine-derived Caco-2 cells with vitamin D(3) markedly
      increased endogenous OATP1A2 mRNA and protein levels. Suppression of endogenous
      vitamin D receptor (VDR) expression with siRNAs significantly reduced this
      induction. Two alternative promoter regions exist in genomic databases for the
      SLCO1A2 gene. One putative VDR response element (VDRE) that was predicted to
      interact efficiently with VDR-retinoid X receptor alpha (RXRalpha) was identified
      in silico within SLCO1A2 promoter variant 1. This VDRE served as a strong binding
      site for the recombinant VDR-RXRalpha heterodimers in vitro and was potently
      activated by VDR in the presence of vitamin D(3) in heterologous promoter assays.
      In reporter assays using native promoter constructs, SLCO1A2 promoter variant 1
      was strongly induced by VDR, and site-directed mutagenesis of a single VDRE
      within this region abolished this activation. Native VDR-RXRalpha also interacted
      with this element both in vitro and in living cells. We showed that expression of
      the SLCO1A2 gene is induced by vitamin D(3) at the transcriptional level through
      the VDR. Our results suggest that pharmacological administration of vitamin D(3)
      may allow modulation of intestinal absorption of OATP1A2 transport substrates.

PMID- 22474173
TI  - Regarding "Dengue--how best to classify it".

PMID- 22474174
TI  - Editorial commentary: Chronic respiratory disease in HIV-infected adolescents.

PMID- 22474176
TI  - Unmet medical need in infectious diseases.

PMID- 22474177
TI  - Chronic lung disease in adolescents with delayed diagnosis of vertically acquired
      HIV infection.
AB  - BACKGROUND: Long-term survivors of vertically acquired human immunodeficiency
      virus (HIV) infection are reaching adolescence in large numbers in Africa and are
      at high risk of delayed diagnosis and chronic complications of untreated HIV
      infection. Chronic respiratory symptoms are more common than would be anticipated
      based on the HIV literature. METHODS: Consecutive adolescents with presumed
      vertically acquired HIV attending 2 HIV care clinics in Harare, Zimbabwe, were
      recruited and assessed with clinical history and examination, CD4 count,
      pulmonary function tests, Doppler echocardiography, and chest radiography (CXR).
      Those with suspected nontuberculous chronic lung disease (CLD) were scanned using
      high-resolution computed tomography (HRCT). RESULTS: Of 116 participants (43%
      male; mean age, 14 +/- 2.6 years, mean age at HIV diagnosis, 12 years), 69% were
      receiving antiretroviral therapy. Chronic cough and reduced exercise tolerance
      were reported by 66% and 21% of participants, respectively; 41% reported multiple
      respiratory tract infections in the previous year, and 10% were clubbed. More
      than 40% had hypoxemia at rest (13%) or on exercise (29%), with pulmonary
      hypertension (mean pulmonary artery pressure >25 mm Hg) in 7%. Forced expiratory
      volume in 1 second (FEV(1)) was <80% predicted in 45%, and 47% had subtle CXR
      abnormalities. The predominant HRCT pattern was decreased attenuation as part of
      a mosaic attenuation pattern (31 of 56 [55%]), consistent with small airway
      disease and associated with bronchiectasis (Spearman correlation coefficient
      (r(2) = 0.8) and reduced FEV(1) (r(2) = -0.26). CONCLUSIONS: Long-term survivors
      of vertically acquired HIV in Africa are at high risk of a previously undescribed
      small airway disease, with >40% of unselected adolescent clinic attendees meeting
      criteria for severe hypoxic CLD. This condition is not obvious at rest. Etiology,
      prognosis, and response to treatment are currently unknown.

PMID- 22474178
TI  - Congenital absence of mitral chordae tendinae on real-time three-dimensional
      transoesophageal echocardiography.

PMID- 22474179
TI  - RNA-Seq analysis of developing nasturtium seeds (Tropaeolum majus):
      identification and characterization of an additional galactosyltransferase
      involved in xyloglucan biosynthesis.
AB  - A deep-sequencing approach was pursued utilizing 454 and Illumina sequencing
      methods to discover new genes involved in xyloglucan biosynthesis. cDNA sequences
      were generated from developing nasturtium (Tropaeolum majus) seeds, which produce
      large amounts of non-fucosylated xyloglucan as a seed storage polymer. In
      addition to known xyloglucan biosynthetic genes, a previously uncharacterized
      putative xyloglucan galactosyltransferase was identified. Analysis of an
      Arabidopsis thaliana mutant line defective in the corresponding ortholog
      (AT5G62220) revealed that this gene shows no redundancy with the previously
      characterized xyloglucan galactosyltransferase, MUR3, but is required for
      galactosyl-substitution of xyloglucan at a different position. The gene was
      termed XLT2 for Xyloglucan L-side chain galactosylTransferase position 2. It
      represents an enzyme in the same subclade of glycosyltransferase family 47 as
      MUR3. A double mutant defective in both MUR3 (mur3.1) and XLT2 led to an
      Arabidopsis plant with xyloglucan that consists essentially of only xylosylated
      glucosyl units, with no further substitutions.

PMID- 22474180
TI  - Differential coloring reveals that plastids do not form networks for exchanging
      macromolecules.
AB  - Stroma-filled tubules named stromules are sporadic extensions of plastids.
      Earlier, photobleaching was used to demonstrate fluorescent protein diffusion
      between already interconnected plastids and formed the basis for suggesting that
      all plastids are able to form networks for exchanging macromolecules. However, a
      critical appraisal of literature shows that this conjecture is not supported by
      unequivocal experimental evidence. Here, using photoconvertible mEosFP, we
      created color differences between similar organelles that enabled us to
      distinguish clearly between organelle fusion and nonfusion events. Individual
      plastids, despite conveying a strong impression of interactivity and fusion,
      maintained well-defined boundaries and did not exchange fluorescent proteins.
      Moreover, the high pleomorphy of etioplasts from dark-grown seedlings,
      leucoplasts from roots, and assorted plastids in the accumulation and replication
      of chloroplasts5 (arc5), arc6, and phosphoglucomutase1 mutants of Arabidopsis
      thaliana suggested that a single plastid unit might be easily mistaken for
      interconnected plastids. Our observations provide succinct evidence to refute the
      long-standing dogma of interplastid connectivity. The ability to create and
      maintain a large number of unique biochemical factories in the form of singular
      plastids might be a key feature underlying the versatility of green plants as it
      provides increased internal diversity for them to combat a wide range of
      environmental fluctuations and stresses.

PMID- 22474181
TI  - CellSeT: novel software to extract and analyze structured networks of plant cells
      from confocal images.
AB  - It is increasingly important in life sciences that many cell-scale and tissue
      scale measurements are quantified from confocal microscope images. However,
      extracting and analyzing large-scale confocal image data sets represents a major
      bottleneck for researchers. To aid this process, CellSeT software has been
      developed, which utilizes tissue-scale structure to help segment individual
      cells. We provide examples of how the CellSeT software can be used to quantify
      fluorescence of hormone-responsive nuclear reporters, determine membrane protein
      polarity, extract cell and tissue geometry for use in later modeling, and take
      many additional biologically relevant measures using an extensible plug-in
      toolset. Application of CellSeT promises to remove subjectivity from the
      resulting data sets and facilitate higher-throughput, quantitative approaches to
      plant cell research.

PMID- 22474183
TI  - Root-derived oxylipins promote green peach aphid performance on Arabidopsis
      foliage.
AB  - Oxylipins function as signaling molecules in plant growth and development and
      contribute to defense against stress. Here, we show that oxylipins also
      facilitate infestation of Arabidopsis thaliana shoots by the phloem sap-consuming
      green peach aphid (GPA; Myzus persicae), an agronomically important insect pest.
      GPAs had difficulty feeding from sieve elements and tapping into the xylem of
      lipoxygenase5 (lox5) mutant plants defective in LOX activity. These defects in
      GPA performance in the lox5 mutant were accompanied by reduced water content of
      GPAs and a smaller population size of GPAs in the mutant compared with the wild
      type plant. LOX5 expression was rapidly induced in roots in response to
      infestation of shoots by GPAs. In parallel, levels of LOX5-derived oxylipins
      increased in roots and in petiole exudates of GPA-colonized plants. Application
      of 9-hydroxyoctadecadienoic acid (an oxylipin produced by the LOX5 enzyme) to
      roots restored water content and GPA population size in lox5 plants, thus
      confirming that a LOX5-derived oxylipin promotes infestation of the foliage by
      GPAs. Micrografting experiments demonstrated that GPA performance on foliage is
      influenced by the LOX5 genotype in roots, thus demonstrating the importance of
      root-derived oxylipins in colonization of aboveground organs by an insect.

PMID- 22474184
TI  - De novo pyrimidine nucleotide synthesis mainly occurs outside of plastids, but a
      previously undiscovered nucleobase importer provides substrates for the essential
      salvage pathway in Arabidopsis.
AB  - Nucleotide de novo synthesis is highly conserved among organisms and represents
      an essential biochemical pathway. In plants, the two initial enzymatic reactions
      of de novo pyrimidine synthesis occur in the plastids. By use of green
      fluorescent protein fusions, clear support is provided for a localization of the
      remaining reactions in the cytosol and mitochondria. This implies that carbamoyl
      aspartate, an intermediate of this pathway, must be exported and precursors of
      pyrimidine salvage (i.e., nucleobases or nucleosides) are imported into plastids.
      A corresponding uracil transport activity could be measured in intact plastids
      isolated from cauliflower (Brassica oleracea) buds. PLUTO (for plastidic
      nucleobase transporter) was identified as a member of the Nucleobase:Cation
      Symporter1 protein family from Arabidopsis thaliana, capable of transporting
      purine and pyrimidine nucleobases. A PLUTO green fluorescent protein fusion was
      shown to reside in the plastid envelope after expression in Arabidopsis
      protoplasts. Heterologous expression of PLUTO in an Escherichia coli mutant
      lacking the bacterial uracil permease uraA allowed a detailed biochemical
      characterization. PLUTO transports uracil, adenine, and guanine with apparent
      affinities of 16.4, 0.4, and 6.3 MUM, respectively. Transport was markedly
      inhibited by low concentrations of a proton uncoupler, indicating that PLUTO
      functions as a proton-substrate symporter. Thus, a protein for the absolutely
      required import of pyrimidine nucleobases into plastids was identified.

PMID- 22474185
TI  - A novel lactone-forming carboxylesterase: molecular identification of a
      tuliposide A-converting enzyme in tulip.
AB  - Tuliposides, the glucose esters of 4-hydroxy-2-methylenebutanoate and 3,4
      dihydroxy-2-methylenebutanoate, are major secondary metabolites in tulip (Tulipa
      gesneriana). Their lactonized aglycons, tulipalins, function as defensive
      chemicals due to their biological activities. We recently found that tuliposide
      converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of
      tuliposides to tulipalins, but the possibility of the presence of several TCE
      isozymes was raised: TCE in tissues other than bulbs is different from bulb TCE.
      Here, to prove this hypothesis, TCE was purified from petals, which have the
      second highest TCE activity after bulbs. The purified enzyme, like the bulb
      enzyme, preferentially accepted tuliposides as substrates, with 6-tuliposide A
      the best substrate, which allowed naming the enzyme tuliposide A-converting
      enzyme (TCEA), but specific activity and molecular mass differed between the
      petal and bulb enzymes. After peptide sequencing, a novel cDNA (TgTCEA) encoding
      petal TCEA was isolated, and the functional characterization of the recombinant
      enzyme verified that TgTCEA catalyzes the conversion of 6-tuliposide A to
      tulipalin A. TgTCEA was transcribed in all tulip tissues but not in bulbs,
      indicating the presence of a bulb-specific TgTCEA, as suggested by the distinct
      enzymatic characters between the petal and bulb enzymes. Plastidial localization
      of TgTCEA enzyme was revealed, which allowed proposing a cytological mechanism of
      TgTCE-mediated tulipalin formation in the tulip defensive strategy. Site-directed
      mutagenesis of TgTCEA suggested that the oxyanion hole and catalytic triad
      characteristic of typical carboxylesterases are essential for the catalytic
      process of TgTCEA enzyme. To our knowledge, TgTCEA is the first identified member
      of the lactone-forming carboxylesterases, specifically catalyzing intramolecular
      transesterification.

PMID- 22474186
TI  - Conditional deletion of beta-catenin in mammary epithelial cells of Ron receptor,
      Mst1r, overexpressing mice alters mammary tumorigenesis.
AB  - The Ron receptor tyrosine kinase (macrophage stimulating 1 receptor) is
      overexpressed in approximately 50% of human breast cancers. Transgenic mice
      overexpressing Ron in the mammary epithelium [mouse mammary tumor virus driven
      (MMTV)-Ron expressing mice] develop mammary tumors that exhibit up-regulation of
      beta-catenin and beta-catenin target genes. beta-Catenin has been shown to be a
      mediator of mammary tumorigenesis in various breast cancer models, including
      downstream of Ron. However, the in vivo impact of a conditional loss of beta
      catenin downstream of Ron receptor overexpression on the onset, growth, turnover,
      and metastasis of mammary tumors has not been addressed. To determine the
      significance of beta-catenin in the context of Ron overexpression, we
      conditionally deleted beta-catenin in mammary epithelial cells of MMTV-Ron mice.
      Conditional deletion of beta-catenin in the mammary epithelium, through the use
      of whey acidic protein (WAP)-Cre transgenic mice, significantly delayed the onset
      of mammary hyperplastic nodules, the presence of palpable mammary tumors, and
      ultimately decreased liver metastasis. beta-Catenin loss in this model was also
      associated with decreased expression of cyclin D1. In total, these studies
      support an important role for beta-catenin downstream of Ron receptor signaling
      during the development of mammary tumorigenesis.

PMID- 22474187
TI  - FGF21 is increased by inflammatory stimuli and protects leptin-deficient ob/ob
      mice from the toxicity of sepsis.
AB  - The acute phase response (APR) produces marked alterations in lipid and
      carbohydrate metabolism including decreasing plasma ketone levels. Fibroblast
      growth factor 21 (FGF21) is a recently discovered hormone that regulates lipid
      and glucose metabolism and stimulates ketogenesis. Here we demonstrate that
      lipopolysaccharide (LPS), zymosan, and turpentine, which induce the APR, increase
      serum FGF21 levels 2-fold. Although LPS, zymosan, and turpentine decrease the
      hepatic expression of FGF21, they increase FGF21 expression in adipose tissue and
      muscle, suggesting that extrahepatic tissues account for the increase in serum
      FGF21. After LPS administration, the characteristic decrease in plasma ketone
      levels is accentuated in FGF21-/- mice, but this is not due to differences in
      expression of carnitine palmitoyltransferase 1alpha or hydroxymethyglutaryl-CoA
      synthase 2 in liver, because LPS induces similar decreases in the expression of
      these genes in FGF21-/- and control mice. However, in FGF21-/- mice, the ability
      of LPS to increase plasma free fatty acid levels is blunted. This failure to
      increase plasma free fatty acid could contribute to the accentuated decrease in
      plasma ketone levels because the transport of fatty acids from adipose tissue to
      liver provides the substrate for ketogenesis. Treatment with exogenous FGF21
      reduced the number of animals that die and the rapidity of death after LPS
      administration in leptin-deficient ob/ob mice and to a lesser extent in control
      mice. FGF21 also protected from the toxic effects of cecal ligation and puncture
      induced sepsis. Thus, FGF21 is a positive APR protein that protects animals from
      the toxic effects of LPS and sepsis.

PMID- 22474189
TI  - The cover. The sun through the trees.

PMID- 22474188
TI  - Differential expression of Wnt signaling molecules between pre- and
      postmenopausal endometrial epithelial cells suggests a population of putative
      epithelial stem/progenitor cells reside in the basalis layer.
AB  - The human endometrium undergoes extensive monthly regeneration in response to
      fluctuating levels of circulating estrogen and progesterone in premenopausal (Pre
      M) women. In contrast, postmenopausal (Post-M) endometrium is thin and quiescent
      with low mitotic activity, similar to the Pre-M endometrial basalis layer.
      Clonogenic epithelial stem/progenitor (ESP) cells, likely responsible for
      regenerating endometrial epithelium, have been identified in Pre-M and Post-M
      endometrium, but their location is unknown. We undertook transcriptional
      profiling of highly purified epithelial cells from full-thickness Pre-M and Post
      M endometrium to identify differentially regulated genes that may indicate a
      putative ESP cell population resides in the basalis of Pre-M and basalis-like
      Post-M endometrium. Of 1077 differentially expressed genes identified, the Wnt
      signaling pathway, important in endometrial development and stem cell regulation,
      was one of the main gene families detected, including 22 Wnt-associated genes.
      Twelve genes were validated using quantitative RT-PCR, and all were concordant
      with microarray data. Immunostaining showed glandular epithelial location of Wnt
      regulated genes, Axin-related protein 2 and beta-catenin. Axin2 localized to the
      nucleus of basalis Pre-M and Post-M and cytoplasm of functionalis Pre-M
      endometrium, suggesting that it regulates beta-catenin. Comparison of our Post-M
      gene profile with published gene microarray datasets revealed similarities to Pre
      M basalis epithelial profiles. This differential expression of multiple Wnt
      associated genes in human Pre-M and Post-M endometrial epithelial cells and the
      similar gene profile of Post-M and Pre-M basalis epithelium suggests that a
      population of putative endometrial ESP may reside in the basalis of Pre-M
      endometrium, which may be responsible for regenerating glandular epithelium each
      month.

PMID- 22474190
TI  - Immunization recommendations expanded for hepatitis B, HPV, pertussis vaccines.

PMID- 22474191
TI  - Medical reserves answer call to service.

PMID- 22474192
TI  - Study: Vast majority of C. difficile infections occur in medical settings.

PMID- 22474193
TI  - Life expectancy after treatment for systolic hypertension.

PMID- 22474194
TI  - Changes in resting heart rate over time and mortality.

PMID- 22474195
TI  - Perceptions of appropriateness of care in the intensive care unit.

PMID- 22474196
TI  - Perceptions of appropriateness of care in the intensive care unit.

PMID- 22474197
TI  - Recommendations on use of prostate-specific antigen for prostate cancer
      screening.

PMID- 22474198
TI  - Incentives in health: different prescriptions for physicians and patients.

PMID- 22474199
TI  - Patient satisfaction, prescription drug abuse, and potential unintended
      consequences.

PMID- 22474200
TI  - The challenge of individualizing treatments for patients with breast cancer.

PMID- 22474201
TI  - A piece of my mind. Filling the void.

PMID- 22474202
TI  - Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on
      survival among patients with resected stage III colon cancer: a randomized trial.
AB  - CONTEXT: Leucovorin, fluorouracil, and oxaliplatin (FOLFOX) is the standard
      adjuvant therapy for resected stage III colon cancer. Adding cetuximab to FOLFOX
      benefits patients with metastatic wild-type KRAS but not mutated KRAS colon
      cancer. OBJECTIVE: To assess the potential benefit of cetuximab added to the
      modified sixth version of the FOLFOX regimen (mFOLFOX6) in patients with resected
      stage III wild-type KRAS colon cancer. DESIGN, SETTING, AND PARTICIPANTS: A
      randomized trial of 2686 patients aged 18 years or older at multiple institutions
      across North America enrolled following resection and informed consent between
      February 10, 2004, and November 25, 2009. The primary randomized comparison was
      12 biweekly cycles of mFOLFOX6 with and without cetuximab. KRAS mutation status
      was centrally determined. The trial was halted after a planned interim analysis
      of 48% of predicted events (246/515) occurring in 1863 (of 2070 planned) patients
      with tumors having wild-type KRAS. A total of 717 patients with mutated KRAS and
      106 with indeterminate KRAS were accrued. The 2070 patients with wild-type KRAS
      provided 90% power to detect a hazard ratio (HR) of 1.33 (2-sided alpha = .05),
      with planned interim efficacy analyses after 25%, 50%, and 75% of expected
      relapses. MAIN OUTCOME MEASURES: Disease-free survival in patients with wild-type
      KRAS mutations. Secondary end points included overall survival and toxicity.
      RESULTS: Median (range) follow-up was 28 (0-68) months. The trial demonstrated no
      benefit when adding cetuximab. Three-year disease-free survival for mFOLFOX6
      alone was 74.6% vs 71.5% with the addition of cetuximab (HR, 1.21; 95% CI, 0.98
      1.49; P = .08) in patients with wild-type KRAS, and 67.1% vs 65.0% (HR, 1.12; 95%
      CI, 0.86-1.46; P = .38) in patients with mutated KRAS, with no significant
      benefit in any subgroups assessed. Among all patients, grade 3 or higher adverse
      events (72.5% vs 52.3%; odds ratio [OR], 2.4; 95% CI, 2.1-2.8; P < .001) and
      failure to complete 12 cycles (33% vs 23%; OR, 1.6; 95% CI, 1.4-1.9; P < .001)
      were significantly higher with cetuximab. Increased toxicity and greater
      detrimental differences in all outcomes were observed in patients aged 70 years
      or older. CONCLUSION: Among patients with stage III resected colon cancer, the
      use of cetuximab with adjuvant mFOLFOX6 compared with mFOLFOX6 alone did not
      result in improved disease-free survival. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00079274.

PMID- 22474203
TI  - Detection of breast cancer with addition of annual screening ultrasound or a
      single screening MRI to mammography in women with elevated breast cancer risk.
AB  - CONTEXT: Annual ultrasound screening may detect small, node-negative breast
      cancers that are not seen on mammography. Magnetic resonance imaging (MRI) may
      reveal additional breast cancers missed by both mammography and ultrasound
      screening. OBJECTIVE: To determine supplemental cancer detection yield of
      ultrasound and MRI in women at elevated risk for breast cancer. DESIGN, SETTING,
      AND PARTICIPANTS: From April 2004-February 2006, 2809 women at 21 sites with
      elevated cancer risk and dense breasts consented to 3 annual independent screens
      with mammography and ultrasound in randomized order. After 3 rounds of both
      screenings, 612 of 703 women who chose to undergo an MRI had complete data. The
      reference standard was defined as a combination of pathology (biopsy results that
      showed in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma
      in the breast or axillary lymph nodes) and 12-month follow-up. MAIN OUTCOME
      MEASURES: Cancer detection rate (yield), sensitivity, specificity, positive
      predictive value (PPV3) of biopsies performed and interval cancer rate. RESULTS:
      A total of 2662 women underwent 7473 mammogram and ultrasound screenings, 110 of
      whom had 111 breast cancer events: 33 detected by mammography only, 32 by
      ultrasound only, 26 by both, and 9 by MRI after mammography plus ultrasound; 11
      were not detected by any imaging screen. Among 4814 incidence screens in the
      second and third years combined, 75 women were diagnosed with cancer.
      Supplemental incidence-screening ultrasound identified 3.7 cancers per 1000
      screens (95% CI, 2.1-5.8; P < .001). Sensitivity for mammography plus ultrasound
      was 0.76 (95% CI, 0.65-0.85); specificity, 0.84 (95% CI, 0.83-0.85); and PPV3,
      0.16 (95% CI, 0.12-0.21). For mammography alone, sensitivity was 0.52 (95% CI,
      0.40-0.64); specificity, 0.91 (95% CI, 0.90-0.92); and PPV3, 0.38 (95% CI, 0.28
      0.49; P < .001 all comparisons). Of the MRI participants, 16 women (2.6%) had
      breast cancer diagnosed. The supplemental yield of MRI was 14.7 per 1000 (95% CI,
      3.5-25.9; P = .004). Sensitivity for MRI and mammography plus ultrasound was 1.00
      (95% CI, 0.79-1.00); specificity, 0.65 (95% CI, 0.61-0.69); and PPV3, 0.19 (95%
      CI, 0.11-0.29). For mammography and ultrasound, sensitivity was 0.44 (95% CI,
      0.20-0.70, P = .004); specificity 0.84 (95% CI, 0.81-0.87; P < .001); and PPV3,
      0.18 (95% CI, 0.08 to 0.34; P = .98). The number of screens needed to detect 1
      cancer was 127 (95% CI, 99-167) for mammography; 234 (95% CI, 173-345) for
      supplemental ultrasound; and 68 (95% CI, 39-286) for MRI after negative
      mammography and ultrasound results. CONCLUSION: The addition of screening
      ultrasound or MRI to mammography in women at increased risk of breast cancer
      resulted in not only a higher cancer detection yield but also an increase in
      false-positive findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00072501.

PMID- 22474204
TI  - Association of diagnostic coding with trends in hospitalizations and mortality of
      patients with pneumonia, 2003-2009.
AB  - CONTEXT: Recent reports suggest that the mortality rate of patients hospitalized
      with pneumonia has steadily declined. While this may be the result of advances in
      clinical care or improvements in quality, it may also represent an artifact of
      changes in diagnostic coding. OBJECTIVE: To compare estimates of trends in
      hospitalizations and inpatient mortality among patients with pneumonia using 2
      approaches to case definition: one limited to patients with a principal diagnosis
      of pneumonia, and another that includes patients with a secondary diagnosis of
      pneumonia if the principal diagnosis is sepsis or respiratory failure. DESIGN,
      SETTING, AND PARTICIPANTS: Trends study using data from the 2003-2009 releases of
      the Nationwide Inpatient Sample. MAIN OUTCOME MEASURES: Change in the annual
      hospitalization rate and change in inpatient mortality over time. RESULTS: From
      2003 to 2009, the annual hospitalization rate for patients with a principal
      diagnosis of pneumonia declined 27.4%, from 5.5 to 4.0 per 1000, while the age-
      and sex-adjusted mortality decreased from 5.8% to 4.2% (absolute risk reduction
      [ARR], 1.6%; 95% CI, 1.4%-1.9%; relative risk reduction [RRR], 28.2%; 95% CI,
      25.2%-31.2%). Over the same period, hospitalization rates of patients with a
      principal diagnosis of sepsis and a secondary diagnosis of pneumonia increased
      177.6% from 0.4 to 1.1 per 1000, while inpatient mortality decreased from 25.1%
      to 22.2% (ARR, 3.0%; 95% CI, 1.6%-4.4%; RRR, 12%; 95% CI, 7.5%-16.1%);
      hospitalization rates for patients with a principal diagnosis of respiratory
      failure and a secondary diagnosis of pneumonia increased 9.3% from 0.44 to 0.48
      per 1000 and mortality declined from 25.1% to 19.2% (ARR, 6.0%; 95% CI, 4.6%
      7.3%; RRR, 23.7%; 95% CI, 19.7%-27.8%). However, when the 3 groups were combined,
      the hospitalization rate declined only 12.5%, from 6.3 to 5.6 per 1000, while the
      age- and sex-adjusted inpatient mortality rate increased from 8.3% to 8.8% (AR
      increase, 0.5%; 95% CI, 0.1%-0.9%; RR increase, 6.0%; 95% CI, 3.3%-8.8%). Over
      this same time frame, the age-, sex-, and comorbidity-adjusted mortality rate
      declined from 8.3% to 7.8% (ARR, 0.5%; 95% CI, 0.2%-0.9%; RRR, 6.3%; 95% CI, 3.8%
      8.8%). CONCLUSIONS: From 2003 to 2009, hospitalization and inpatient mortality
      rates for patients with a principal diagnosis of pneumonia decreased
      substantially, whereas hospitalizations with a principal diagnosis of sepsis or
      respiratory failure accompanied by a secondary diagnosis of pneumonia increased
      and mortality declined. However, when the 3 pneumonia diagnoses were combined,
      the decline in the hospitalization rate was attenuated and inpatient mortality
      was little changed, suggesting an association of these results with temporal
      trends in diagnostic coding.

PMID- 22474205
TI  - Oral fluoroquinolones and the risk of retinal detachment.
AB  - CONTEXT: Fluoroquinolones are commonly prescribed classes of antibiotics. Despite
      numerous case reports of ocular toxicity, a pharmacoepidemiological study of
      their ocular safety, particularly retinal detachment, has not been performed.
      OBJECTIVE: To examine the association between use of oral fluoroquinolones and
      the risk of developing a retinal detachment. DESIGN, SETTING, AND PATIENTS:
      Nested case-control study of a cohort of patients in British Columbia, Canada,
      who had visited an ophthalmologist between January 2000 and December 2007.
      Retinal detachment cases were defined as a procedure code for retinal repair
      surgery within 14 days of a physician service code. Ten controls were selected
      for each case using risk-set sampling, matching on age and the month and year of
      cohort entry. MAIN OUTCOME MEASURE: The association between retinal detachment
      and current, recent, or past use of an oral fluoroquinolone. RESULTS: From a
      cohort of 989,591 patients, 4384 cases of retinal detachment and 43,840 controls
      were identified. Current use of fluoroquinolones was associated with a higher
      risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls;
      adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of
      cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of
      cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a
      retinal detachment. The absolute increase in the risk of a retinal detachment was
      4 per 10,000 person-years (number needed to harm = 2500 computed for any use of
      fluoroquinolones). There was no evidence of an association between development of
      a retinal detachment and beta-lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57])
      or short-acting beta-agonists (ARR, 0.95 [95% CI, 0.68-1.33]). CONCLUSION:
      Patients taking oral fluoroquinolones were at a higher risk of developing a
      retinal detachment compared with nonusers, although the absolute risk for this
      condition was small.

PMID- 22474206
TI  - Update: A 41-year-old woman with menorrhagia, anemia, and fibroids: review of
      treatment of uterine fibroids.

PMID- 22474207
TI  - Antitumor activity in metastatic disease does not predict efficacy in the
      adjuvant setting.

PMID- 22474208
TI  - Finding pure and simple truths with administrative data.

PMID- 22474209
TI  - JAMA patient page. Retinal detachment.

PMID- 22474210
TI  - Pro: the arteriovenous fistula is a blessing of God.

PMID- 22474211
TI  - Is Cystatin C a promising marker of renal function, at birth, in neonates
      prenatally diagnosed with congenital kidney anomalies?
AB  - BACKGROUND: Despite the increased prenatal diagnosis of congenital abnormalities
      of the kidney and urinary tract (CAKUT), no reliable renal marker for glomerular
      filtration rate (GFR) has been validated yet in neonates. Cystatin C (CysC) is
      specific to the neonate and is proposed as a sensitive marker for this
      population. The aims of the study were first to define a reference interval in
      our center of CysC at birth in normal term babies and assess CysC as a marker of
      GFR in a group of term neonates prenatally diagnosed with CAKUT compared to
      controls. METHODS: One hundred normal term neonates (control group) and 33
      neonates with kidney malformation (KM) had the CysC levels in their cord blood
      measured. A reference interval for CysC in controls was calculated using non
      parametric methods. CysC from controls was compared first to the whole group of
      neonates with KM, then with KM group divided in infants (n = 20) with unilateral
      kidney malformation (UKM) and those (n = 13) with bilateral kidney malformation
      (BKM). A multivariable analysis was performed to assess the difference in CysC
      between the groups with adjustment on other factors. The ability of CysC to
      discriminate neonates with BKM from the controls was assessed by a non-parametric
      receiver-operated characteristics (ROC) curve. RESULTS: In the control group, the
      CysC reference interval was [1.54-2.64] mg/L with a median (M) CysC of 2.02 IQR
      [1.86-2.23]. In the neonates with KM, M CysC was 1.98 IQR [1.79-2.34]; 1.88 IQR
      [1.76-2.01] in the UKM group and 2.52 IQR [2.16-2.71] in BKM group. Using a
      multivariate regression analyses, CysC was significantly increased (P < 0.001) in
      BKM compared to controls with an increment of CysC of 24.5%, and independent from
      gender, weight and size. The ROC curve analyses, comparing BKM versus controls
      with a chosen cut-off for CysC of 2.34, showed a sensitivity of 69% and a
      specificity of 86%. CONCLUSIONS: Comparing CysC with a reference interval of CysC
      validated in our center, we showed a significant increase of CysC in neonates
      presenting BKM compared to controls and those with UKM.

PMID- 22474212
TI  - Predicting lower third molar eruption on panoramic radiographs after
      cephalometric comparison of profile and panoramic radiographs.
AB  - Previous studies have suggested methods for predicting third molar tooth eruption
      radiographically. Still, this prediction is associated with uncertainty. The aim
      of the present study was to elucidate the association between cephalometric
      measurements on profile and panoramic radiographs and to find a simple and
      reliable method for predicting the eruption of the mandibular third molar by
      measurements on panoramic radiographs. The material consisted of profile and
      panoramic radiographs, taken before orthodontic treatment, of 30 males and 23
      females (median age 22, range 18-48 years), with no known diseases. Cephalometric
      measurements on panoramic and profile radiographs were performed and compared,
      i.e. the size of the gonial angle and sagittal distance from the alveolar margin
      between the mandibular central incisors to the anterior border of the mandibular
      ramus. Furthermore, the mesiodistal width of the second molar was measured.
      Statistical methods included analysis of method error. The probability of
      eruption was modelled using logistic regression analysis. Correlation was
      observed between all measurements on profile and panoramic radiographs. The
      skeletal variable expressing the length from the ramus to the incisors (olr-id)
      showed a statistically significant correlation. By combining this length with the
      mesiodistal width of the lower second molar, the prediction of eruption of the
      lower third molar was strengthened. A new formula for calculating the probability
      of eruption of the mandibular third molar was made and a graph constructed for
      easy assessment. In conclusion, a simple method for predicting the eruption of
      the third molar is presented. 

PMID- 22474213
TI  - Visual outcomes in children with neurofibromatosis type 1-associated optic
      pathway glioma following chemotherapy: a multicenter retrospective analysis.
AB  - Optic pathway gliomas (OPGs) occur in 15%-20% of children with neurofibromatosis
      type 1 (NF1); up to half become symptomatic. There is little information
      regarding ophthalmologic outcomes after chemotherapy. A retrospective multicenter
      study was undertaken to evaluate visual outcomes following chemotherapy for NF1
      associated OPG, to identify risks for visual loss, and to ascertain indications
      for treatment. Subjects included children undergoing initial treatment for OPGs
      with chemotherapy between January 1997 and December 2007. Of 115 subjects, visual
      acuity (VA) decline and tumor progression were the primary reasons to initiate
      treatment, although there were significant differences in the pattern of
      indications cited among the institutions. Eighty-eight subjects and 168 eyes were
      evaluable for VA outcome. At completion of chemotherapy, VA improved (32% of
      subjects), remained stable (40%), or declined (28%). Tumor location was the most
      consistent prognostic factor for poor VA outcome. There was poor correlation
      between radiographic and VA outcomes. Although visual outcomes for NF1-associated
      OPG are not optimal, approximately one-third of children regain some vision with
      treatment. Since radiographic outcomes do not predict visual outcomes, their use
      as the primary measure of treatment success is in question. The lack of consensus
      regarding the indications for treatment underlines the need for better
      standardization of care. Future clinical trials for OPG require standardized
      visual assessment methods and clear definitions of visual outcomes.

PMID- 22474214
TI  - Validation of a fully automated robotic setup for preparation of whole blood
      samples for LC-MS toxicology analysis.
AB  - A fully automated setup was developed for preparing whole blood samples using a
      Tecan Evo workstation. By integrating several add-ons to the robotic platform,
      the flexible setup was able to prepare samples from sample tubes to a 96-well
      sample plate ready for injection on liquid chromatography-mass spectrometry using
      several preparation techniques, including protein precipitation, solid-phase
      extraction and centrifugation, without any manual intervention. Pipetting of a
      known aliquot of whole blood was achieved by integrating a balance and performing
      gravimetric measurements. The system was able to handle 1,073 of 1,092 (98.3%)
      samples of whole blood from forensic material, including postmortem samples,
      without any need for repeating sample preparation. Only three samples required
      special treatment such as dilution. The addition of internal and calibration
      standards were validated by pipetting a solution of Orange G and measuring the
      weight and absorbance. Internal standard (20 uL) was added in a multi-pipetting
      sequence with an accuracy of 99.9% and imprecision (coefficient of variation) of
      1.6%. Calibration standards were added with high accuracy at volumes as low as
      6.00 uL (+/-0.21 uL). The general setup of the offline sample preparation and key
      validation parameters of a quantitative analysis of Delta(9)-tetrahydrocannabinol
      is presented.

PMID- 22474215
TI  - The analysis of protein-bound thiocyanate in plasma of smokers and non-smokers as
      a marker of cyanide exposure.
AB  - When cyanide is introduced into the body, it quickly transforms through a variety
      of chemical reactions, normally involving sulfur donors, to form more stable
      chemical species. Depending on the nature of the sulfur donor, cyanide may be
      transformed into free thiocyanate, the major metabolite of cyanide
      transformation, 2-amino-2-thiazoline-4-carboxylic acid or protein-bound
      thiocyanate (PB-SCN) adducts. Because protein adducts are generally stable in
      biological systems, it has been suggested that PB-SCN may have distinct
      advantages as a marker of cyanide exposure. In this study, plasma was analyzed
      from 25 smokers (chronic low-level cyanide exposure group) and 25 non-smokers for
      PB-SCN. The amount of PB-SCN found in the plasma of smokers, 1.35 uM, was
      significantly elevated (p < 0.0001) when compared to non-smokers, 0.66 uM.
      Differences in sub-groups of smokers and non-smokers were also evaluated. The
      results of this study indicate the effectiveness of analyzing PB-SCN in
      determining instances of chronic cyanide exposure with possible extension to
      confirmation of acute cyanide exposure.

PMID- 22474216
TI  - The helicase and RNaseIIIa domains of Arabidopsis Dicer-Like1 modulate catalytic
      parameters during microRNA biogenesis.
AB  - Dicer-Like1 (DCL1), an RNaseIII endonuclease, and Hyponastic Leaves1 (HYL1), a
      double-stranded RNA-binding protein, are core components of the plant microRNA
      (miRNA) biogenesis machinery. hyl1 null mutants accumulate low levels of miRNAs
      and display pleiotropic developmental phenotypes. We report the identification of
      five new hyl1 suppressor mutants, all of which are alleles of DCL1. These new
      alleles affect either the helicase or the RNaseIIIa domains of DCL1, highlighting
      the critical functions of these domains. Biochemical analysis of the DCL1
      suppressor variants reveals that they process the primary transcript (pri-miRNA)
      more efficiently than wild-type DCL1, with both higher K(cat) and lower K(m)
      values. The DCL1 variants largely rescue wild-type miRNA accumulation levels in
      vivo, but do not rescue the MIRNA processing precision defects of the hyl1 null
      mutant. In vitro, the helicase domain confers ATP dependence on DCL1-catalyzed
      MIRNA processing, attenuates DCL1 cleavage activity, and is required for precise
      MIRNA processing of some substrates.

PMID- 22474217
TI  - Genetic analysis of strawberry fruit aroma and identification of O
      methyltransferase FaOMT as the locus controlling natural variation in mesifurane
      content.
AB  - Improvement of strawberry (Fragaria * ananassa) fruit flavor is an important goal
      in breeding programs. To investigate genetic factors controlling this complex
      trait, a strawberry mapping population derived from genotype '1392', selected for
      its superior flavor, and '232' was profiled for volatile compounds over 4 years
      by headspace solid phase microextraction coupled to gas chromatography and mass
      spectrometry. More than 300 volatile compounds were detected, of which 87 were
      identified by comparison of mass spectrum and retention time to those of pure
      standards. Parental line '1392' displayed higher volatile levels than '232', and
      these and many other compounds with similar levels in both parents segregated in
      the progeny. Cluster analysis grouped the volatiles into distinct chemically
      related families and revealed a complex metabolic network underlying volatile
      production in strawberry fruit. Quantitative trait loci (QTL) detection was
      carried out over 3 years based on a double pseudo-testcross strategy. Seventy
      QTLs covering 48 different volatiles were detected, with several of them being
      stable over time and mapped as major QTLs. Loci controlling gamma-decalactone and
      mesifurane content were mapped as qualitative traits. Using a candidate gene
      approach we have assigned genes that are likely responsible for several of the
      QTLs. As a proof of concept we show that one homoeolog of the O-methyltransferase
      gene (FaOMT) is the locus responsible for the natural variation of mesifurane
      content. Sequence analysis identified 30 bp in the promoter of this FaOMT
      homoeolog containing putative binding sites for basic/helix-loop-helix, MYB, and
      BZIP transcription factors. This polymorphism fully cosegregates with both the
      presence of mesifurane and the high expression of FaOMT during ripening.

PMID- 22474218
TI  - Studies on subcellular compartmentalization of plant pathogenic noncoding RNAs
      give new insights into the intracellular RNA-traffic mechanisms.

PMID- 22474219
TI  - Acquired epidermodysplasia verruciformis due to multiple and unusual HPV
      infection among vertically-infected, HIV-positive adolescents in Zimbabwe.
AB  - BACKGROUND: We have previously described the presentation of epidermodysplasia
      verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents
      with vertically-acquired human immunodeficiency virus (HIV) infection in Harare,
      Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed
      a clinical case note review and skin biopsy from affected sites in 4 HIV-infected
      adolescents with EV-like lesions in Harare. Biopsies were processed for histology
      and for human papillomavirus (HPV) typing. RESULTS: All patients had long
      standing skin lesions that pre-dated the diagnosis of HIV by several years. The
      histology of skin biopsies from all patients was consistent with EV. In each
      biopsy, EV-associated beta-HPV type 5 was identified (additionally, type 19 was
      found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in
      all biopsies, together with genital lesion-associated HPV types 6, 16, and 52,
      (as well as >=3 other genital lesion-associated HPV types). Despite immune
      reconstitution with combination antiretroviral therapy (cART), there was no
      improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring
      and potentially stigmatizing condition among this patient group and is difficult
      to treat; cART appears to have no impact on the progression of skin disease.
      Among adolescents with longstanding HIV-induced immunosuppression and with high
      levels of sun exposure, close dermatological surveillance for potential skin
      malignancy is required.

PMID- 22474220
TI  - Increased and expedited case detection by Xpert MTB/RIF assay in childhood
      tuberculosis: a prospective cohort study.
AB  - BACKGROUND: Diagnosis and timely treatment of tuberculosis in children is
      hampered by the absence of fast and reliable tests, especially in the era of
      human immunodeficiency virus (HIV). The aim of this study was to evaluate the
      diagnostic performance of the Xpert MTB/RIF assay (Xpert) in children with
      suspected tuberculosis in a high tuberculosis/HIV-burden setting. METHODS: In a
      prospective study with a minimum follow-up of 12 months, 164 children with
      suspected tuberculosis were assigned to predefined diagnostic subgroups, based on
      microbiological and clinical findings. Results of smear microscopy and culture
      were compared against diagnostic performance of Xpert. RESULTS: Twenty-eight of
      164 children (17.1%) had confirmed tuberculosis. Xpert detected 100% (95%
      confidence interval [CI], 59.0%-100%) of smear-positive cases and 66.6% (95% CI,
      43.0%-85.4%) of culture-positive but smear-negative cases. In the per-sample
      analysis, Xpert displayed a similar sensitivity (54.7% [95% CI, 42.7%-66.2%])
      compared with culture methods. Xpert detected 3-fold more confirmed tuberculosis
      cases than smear microscopy but with equal rapidity. Four additional cases (8.5%)
      with clinical tuberculosis but negative culture were diagnosed by Xpert. Testing
      second and third samples increased sensitivity by 20% and an additional 16%,
      respectively. When tuberculosis was reliably excluded, Xpert's specificity was
      100%. HIV infection did not affect diagnostic accuracy of Xpert. CONCLUSIONS:
      Xpert was easy to perform and displayed similar diagnostic accuracy as culture
      methods in children with suspected tuberculosis. Rapid turnaround times should
      reduce treatment delay and improve patient outcome, although sensitivity remains
      suboptimal and access is dependent on local laboratory infrastructure.

PMID- 22474221
TI  - Staphylococcus aureus colonization among household contacts of patients with skin
      infections: risk factors, strain discordance, and complex ecology.
AB  - BACKGROUND: The USA300 methicillin resistant Staphylococcus aureus (MRSA) genetic
      background has rapidly emerged as the predominant cause of community-associated
      S. aureus infections in the U.S. However, epidemiologic characteristics of S.
      aureus household transmission are poorly understood. METHODS: We performed a
      cross-sectional study of adults and children with S. aureus skin infections and
      their household contacts in Los Angeles and Chicago. Subjects were surveyed for
      S. aureus colonization of the nares, oropharynx, and inguinal region and risk
      factors for S. aureus disease. All isolates underwent genetic typing. RESULTS: We
      enrolled 1162 persons (350 index patients and 812 household members). The most
      common infection isolate characteristic was ST8/SCCmec IV, PVL+ MRSA (USA300)
      (53%). S. aureus colonized 40% (137/350) of index patients and 50% (405/812) of
      household contacts. A nares-only survey would have missed 48% of S. aureus and
      51% of MRSA colonized persons. Sixty-five percent of households had >1 S. aureus
      genetic background identified and 26% of MRSA isolates in household contacts were
      discordant with the index patients' infecting MRSA strain type. Factors
      independently associated (P < .05) with the index strain type colonizing
      household contacts were recent skin infection, recent cephalexin use, and USA300
      genetic background. CONCLUSIONS: In our study population, USA300 MRSA appeared
      more transmissible among household members compared with other S. aureus genetic
      backgrounds. Strain distribution was complex; >1 S. aureus genetic background was
      present in many households. S. aureus decolonization strategies may need to
      address extra-nasal colonization and the consequences of eradicating S. aureus
      genetic backgrounds infrequently associated with infection.

PMID- 22474222
TI  - Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART)
      failure in 6 sub-Saharan African countries: implications for second-line ART
      strategies.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit
      the benefits of antiretroviral therapy (ART). This cohort study examined patterns
      of drug-resistance mutations (DRMs) in individuals with virological failure on
      first-line ART at 13 clinical sites in 6 African countries and predicted their
      impact on second-line drug susceptibility. METHODS: A total of 2588
      antiretroviral-naive individuals initiated ART consisting of different nucleoside
      reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine,
      tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz
      or nevirapine. Population sequencing after 12 months of ART was retrospectively
      performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral
      Society-USA list was used to score major DRMs. The Stanford algorithm was used to
      predict drug susceptibility. RESULTS: HIV-1 sequences were generated for 142
      participants who virologically failed ART, of whom 70% carried >=1 DRM and 49%
      had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8).
      The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A
      (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently
      selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with >=1
      DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for
      lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for
      tenofovir, in 18% for stavudine, and in 10% for zidovudine. CONCLUSIONS: Early
      failure detection limited the accumulation of resistance. After stavudine failure
      in African populations, zidovudine rather than tenofovir may be preferred in
      second-line ART. Strategies to prevent HIV-1 resistance are a global priority.

PMID- 22474223
TI  - Systemic shigellosis in South Africa.
AB  - BACKGROUND: Systemic disease due to shigellae is associated with human
      immunodeficiency virus (HIV), malnutrition, and other immunosuppressed states. We
      examined the clinical and microbiologic characteristics of systemic shigellosis
      in South Africa, where rates of HIV infection are high. METHODS: From 2003 to
      2009, 429 cases of invasive shigellosis were identified through national
      laboratory-based surveillance. At selected sites, additional information was
      captured on HIV serostatus and outcome. Isolates were serotyped and antimicrobial
      susceptibility testing performed. RESULTS: Most cases of systemic shigellosis
      were diagnosed on blood culture (408 of 429 cases; 95%). HIV prevalence was 67%
      (80 of 120 cases), highest in patients aged 5-54 years, and higher among females
      (55 of 70 cases; 79%) compared with males (25 of 48 cases; 52%; P = .002). HIV
      infected people were 4.1 times more likely to die than HIV-uninfected cases (case
      fatality ratio, 29 of 78 HIV-infected people [37%] vs 5 of 40 HIV-uninfected
      people [13%]; P = .008; 95% confidence interval [CI], 1.5-11.8). The commonest
      serotype was Shigella flexneri 2a (89 of 292 serotypes [30.5%]). Pentavalent
      resistance occurred in 120 of 292 isolates (41.1%). There was no difference in
      multidrug resistance between HIV-infected patients (33 of 71 [46%]) and
      uninfected patients (12 of 33 [36%]; 95% CI, .65--3.55). CONCLUSIONS: Systemic
      shigellosis is associated with HIV-infected patients, primarily in older girls
      and women, potentially due to the burden of caring for sick children in the home;
      interventions need to be targeted here. Death rates are higher in HIV-infected
      versus uninfected individuals.

PMID- 22474224
TI  - The cost-effectiveness of pre-exposure prophylaxis for HIV infection in South
      African women.
AB  - BACKGROUND: Recent trials report the short-term efficacy of tenofovir-based pre
      exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus (HIV)
      infection. PrEP's long-term impact on patient outcomes, population-level
      transmission, and cost-effectiveness remains unknown. METHODS: We linked data
      from recent trials to a computer model of HIV acquisition, screening, and care to
      project lifetime HIV risk, life expectancy (LE), costs, and cost-effectiveness,
      using 2 PrEP-related strategies among heterosexual South African women: (1) women
      receiving no PrEP and (2) women not receiving PrEP (a tenofovir-based vaginal
      microbicide). We used a South African clinical cohort and published data to
      estimate population demographic characteristics, age-adjusted incidence of HIV
      infection, and HIV natural history and treatment parameters. Baseline PrEP
      efficacy (percentage reduction in HIV transmission) was 39% at a monthly cost of
      $5 per woman. Alternative parameter values were examined in sensitivity analyses.
      RESULTS: Among South African women, PrEP reduced mean lifetime HIV risk from 40%
      to 27% and increased population discounted (undiscounted) LE from 22.51 (41.66)
      to 23.48 (44.48) years. Lifetime costs of care increased from $7280 to $9890 per
      woman, resulting in an incremental cost-effectiveness ratio of $2700/year of life
      saved, and may, under optimistic assumptions, achieve cost savings. Under
      baseline HIV infection incidence assumptions, PrEP was not cost saving, even
      assuming an efficacy >60% and a cost <$1. At an HIV infection incidence of
      9.1%/year, PrEP achieved cost savings at efficacies >=50%. CONCLUSIONS: PrEP in
      South African women is very cost-effective by South African standards, conferring
      excellent value under virtually all plausible data scenarios. Although optimistic
      assumptions would be required to achieve cost savings, these represent important
      benchmarks for future PrEP study design.

PMID- 22474225
TI  - Seasonality of tuberculosis in the United States, 1993-2008.
AB  - BACKGROUND: Although seasonal variation in tuberculosis incidence has been
      described in several recent studies, the mechanism underlying this seasonality
      remains unknown. Seasonality of tuberculosis disease may indicate the presence of
      season-specific risk factors that could potentially be controlled if they were
      better understood. We conducted this study to determine whether tuberculosis is
      seasonal in the United States and to describe patterns of seasonality in specific
      populations. METHODS: We performed a time series decomposition analysis of
      tuberculosis cases reported to the Centers for Disease Control and Prevention
      from 1993 through 2008. Seasonal amplitude of tuberculosis disease (the
      difference between the months with the highest and lowest mean case counts), was
      calculated for the population as a whole and for populations with select
      demographic, clinical, and epidemiologic characteristics. RESULTS: A total of 243
      432 laboratory-confirmed tuberculosis cases were reported over a period of 16
      years. A mean of 21.4% more cases were diagnosed in March, the peak month,
      compared with November, the trough month. The magnitude of seasonality did not
      vary with latitude. The greatest seasonal amplitude was found among children aged
      <5 years and in cases associated with disease clusters. CONCLUSIONS: Tuberculosis
      is a seasonal disease in the United States, with a peak in spring and trough in
      late fall. The latitude independence of seasonality suggests that reduced winter
      sunlight exposure may not be a strong contributor to tuberculosis risk. Increased
      seasonality among young children and clustered cases suggests that disease that
      is the result of recent transmission is more influenced by season than disease
      resulting from activation of latent infection.

PMID- 22474226
TI  - Hitting the target: where do molecularly targeted therapies fit in the treatment
      scheduling of neuroendocrine tumours?
AB  - Neuroendocrine tumours (NETs) are a rare and heterogeneous group of tumours whose
      incidence is increasing and their prevalence is now greater than that of any
      other upper gastrointestinal tumour. Diagnosis can be challenging, and up to 25%
      of patients present with metastatic disease. Following the recent FDA approval of
      two new molecularly targeted therapies for the treatment of advanced pancreatic
      NETs (pNETs), the first in 25 years, we review all systemic therapies and suggest
      where these newer targeted therapies fit in the treatment schedule for these
      challenging tumours. Clinical trial data relating to the routine use of sunitinib
      and everolimus in low-intermediate-grade pNETs are summarised alongside newer
      molecularly targeted agents undergoing clinical assessment in NETs. We
      particularly focus on the challenge of optimal scheduling of molecularly targeted
      treatments around existing systemic and localised treatment such as chemotherapy
      or radiotargeted therapy. We also discuss application of current evidence to
      subgroups of patients who have not so far been directly addressed such as those
      with poorer performance status or patients receiving radical surgery who may
      benefit from adjuvant treatment.

PMID- 22474228
TI  - Whole genome expression differences in human left and right atria ascertained by
      RNA sequencing.
AB  - BACKGROUND: The left and right atria have different susceptibilities toward
      developing arrhythmias, with left atrial arrhythmias more commonly observed. To
      understand the molecular basis for such differences, we catalogued micro (mi)RNA
      and mRNA expression differences by next generation sequencing. METHODS AND
      RESULTS: Four human left-right atrial pairs were subjected to whole-genome
      expression analyses via next-generation sequencing of small RNAs, including
      miRNAs, and poly-A-enriched mRNAs. Using a paired sample design, significant
      differences in the expression of 32 miRNAs were found in between the left and
      right atria at a probability value of <0.01. Hsa-miR-143 was the most highly
      expressed miRNA in the atria, as quantified by RNA sequencing. There were 746 and
      2292 differentially expressed mRNAs between the left and right atria at false
      discovery rates of <0.001 and <0.05, respectively. Transcription factor binding
      elements within 2 kb of RefSeq genes were determined and specific motifs were
      identified that were enriched in differentially expressed genes. Similarly,
      specific miRNA target sequences in 3' UTRs were also enriched in differentially
      expressed genes. In addition, 11 novel noncoding RNAs of unknown function were
      found to be differentially expressed between the left and right atria.
      CONCLUSIONS: There are significant differences in miRNA and mRNA expression
      profiles between the left and right atria, which may yield insight into increased
      the arrhythmogenesis of the left atria.

PMID- 22474229
TI  - Mental health problems in children and young people from minority ethnic groups:
      the need for targeted research.
AB  - In this editorial we argue for the need for better research evidence on the
      prevalence of child mental health problems in minority ethnic groups, service
      utilisation among these groups and whether some service barriers are specific for
      certain groups. Without such evidence it is not possible to influence policy and
      practice so that evidence-based and appropriate services can be designed and
      offered to these populations. The terms ethnicity, race and migration are often
      imprecisely defined, and mental health needs and outcomes vary between immigrants
      from different generations. There is also a complex interplay between minority
      status and social class, with terms such as ethnicity being a proxy for
      multifaceted sociocultural and economic variables. However, we need to start
      collecting better data on children from minority ethnic groups so that these
      relationships can be understood, services tailored on the available evidence and
      ultimately better care delivered to this group of children.

PMID- 22474227
TI  - Whole exome sequencing to identify a novel gene (caveolin-1) associated with
      human pulmonary arterial hypertension.
AB  - BACKGROUND: Heritable and idiopathic pulmonary arterial hypertension (PAH) are
      phenotypically identical and associated with mutations in several genes related
      to transforming growth factor (TGF) beta signaling, including bone morphogenetic
      protein receptor type 2, activin receptor-like kinase 1, endoglin, and mothers
      against decapentaplegic 9. Approximately 25% of heritable cases lack identifiable
      mutations in any of these genes. METHODS AND RESULTS: We used whole exome
      sequencing to study a 3-generation family with multiple affected family members
      with PAH, but no identifiable TGF beta mutation. We identified a frameshift
      mutation in caveolin-1 (CAV1), which encodes a membrane protein of caveolae
      abundant in the endothelium and other cells of the lung. An independent de novo
      frameshift mutation was identified in a child with idiopathic PAH. Western blot
      analysis demonstrated a reduction in caveolin-1 protein, while lung tissue
      immunostaining studies demonstrated a reduction in normal caveolin-1 density
      within the endothelial cell layer of small arteries. CONCLUSIONS: Our study
      represents successful elucidation of a dominant Mendelian disorder using whole
      exome sequencing. Mutations in CAV1 are associated in rare cases with PAH. This
      may have important implications for pulmonary vascular biology, as well as PAH
      directed therapeutic development.

PMID- 22474230
TI  - Intellectual disability and major psychiatric disorders: a continuum of
      neurodevelopmental causality.
AB  - There is accumulating evidence for shared genetic as well as environmental risk
      between intellectual disability and other conditions with a neurodevelopmental
      basis such as autism, attention-deficit hyperactivity disorder, epilepsy and
      schizophrenia. These can be conceived as lying along a continuum of genetically
      and environmentally induced neurodevelopmental causality.

PMID- 22474231
TI  - Third-generation neuroimaging in early schizophrenia: translating research
      evidence into clinical utility.
AB  - Psychiatric imaging needs to move away from simple investigations of the
      neurobiology underlying the early phases of schizophrenia to translate imaging
      findings in the clinical field, targeting clinical outcomes including transition,
      remission and response to preventive interventions.

PMID- 22474232
TI  - Sleep in schizophrenia: time for closer attention.
AB  - Recent sleep research has highlighted two specific anomalies in schizophrenia
      that have a proven impact on cognition. One is an abnormality of circadian
      rhythm, reported in this journal in two separate studies over the past year, and
      the other is the finding in electroencephalograms of reduced sleep spindles.

PMID- 22474233
TI  - Phenomenology of depression in older compared with younger adults: meta-analysis.
AB  - BACKGROUND: Late-life depression may differ from early-life depression in its
      phenomenology. AIMS: To investigate the effect of age on the phenomenology of
      major depression. METHOD: A systematic search was conducted in PubMed, Embase and
      PsycINFO for all studies examining the relation between age and phenomenology of
      major depression according to RDC, DSM and ICD criteria. Studies were included
      only if the age groups were compared at the single-item level using the 17-, 21-
      or 24-item versions of the Hamilton Rating Scale for Depression; a meta-analysis
      was done for each item of the 17-item scale. RESULTS: Eleven papers met the
      inclusion criteria. Older depressed adults, compared with younger depressed
      adults, demonstrated more agitation, hypochondriasis and general as well as
      gastrointestinal somatic symptoms, but less guilt and loss of sexual interest.
      CONCLUSIONS: The phenomenology of late-life depression differs only in part from
      that of early-life depression. Major depression in older people may have a more
      somatic presentation, whereas feelings of guilt and loss of sexual function may
      be more prevalent in younger people.

PMID- 22474234
TI  - Antibody-mediated encephalitis and psychosis.

PMID- 22474236
TI  - Occipital transcranial magnetic stimulation in dementia with Lewy bodies.

PMID- 22474238
TI  - Creativity and mental disorder.

PMID- 22474239
TI  - Creativity and mental disorder.

PMID- 22474240
TI  - Creativity and mental disorder.

PMID- 22474242
TI  - Complete absence of evening melatonin increase in tetraplegics.
AB  - Individuals with a spinal cord injury (SCI), especially with tetraplegia,
      experience poor sleep quality, and this may be related to impaired control of
      circadian rhythmicity. Here, we examined the evening onset of melatonin
      secretion, an important hormone for the initiation of sleep, in people with a
      complete cervical (tetraplegia) and thoracic (paraplegia) SCI, and age- and sex
      matched able-bodied control participants. Multiple samples of salivary melatonin
      were obtained during the evening hours and analyzed by ELISA methods in 10
      control partcipants, 9 individuals with paraplegia, and 6 individuals with
      tetraplegia. Sleep quality was assessed using questionnaires. Interactive effects
      of group and time were found for melatonin levels (P=0.022). In the control and
      paraplegia groups, the mean melatonin level increased significantly from 2.59 +/-
      1.04 and 4.28 +/- 3.28 pg/ml at 7 PM to 10.62 +/- 4.59 and 13.10 +/- 7.39 pg/ml
      at 11 PM, respectively (P<0.001). In the tetraplegia group, melatonin level was
      5.25 +/- 3.72 at 7 PM but only 2.41 +/- 1.25 pg/ml at 11 PM (P>0.05). Decreased
      sleep quality was more prevalent in individuals with tetraplegia (83%) and
      paraplegia (75%) compared with controls (20%; P=0.02). Unlike in the control and
      paraplegia groups, the evening increase in melatonin concentration was completely
      absent in the tetraplegia group. This provides biological insight into sleep
      regulation in humans and provides better understanding of the poor sleep quality
      in people with tetraplegia.

PMID- 22474243
TI  - Enhanced Ca2+ entry and Na+/Ca2+ exchanger activity in dendritic cells from AMP
      activated protein kinase-deficient mice.
AB  - In dendritic cells (DCs), chemotactic chemokines, such as CXCL12, rapidly
      increase cytosolic Ca(2+)concentrations ([Ca(2+)](i)) by triggering Ca(2+)
      release from intracellular stores followed by store-operated Ca(2+) (SOC) entry.
      Increase of [Ca(2+)](i) is blunted and terminated by Ca(2+) extrusion,
      accomplished by K(+)-independent Na(+)/Ca(2+) exchangers (NCXs) and K(+)
      dependent Na(+)/Ca(2+) exchangers (NCKXs). Increased [Ca(2+)](i) activates energy
      sensing AMP-activated protein kinase (AMPK), which suppresses proinflammatory
      responses of DCs and macrophages. The present study explored whether AMPK
      participates in the regulation of DC [Ca(2+)](i) and migration. DCs were isolated
      from AMPKalpha1-deficient (ampk(-/-)) mice and, as control, from their wild-type
      (ampk(+/+)) littermates. AMPKalpha1, Orai1-2, STIM1-2, and mitochondrial calcium
      uniporter protein expression was determined by Western blotting, [Ca(2+)](i) by
      Fura-2 fluorescence, SOC entry by inhibition of endosomal Ca(2+) ATPase with
      thapsigargin (1 MUM), Na(+)/Ca(2+) exchanger activity from increase of
      [Ca(2+)](i), and respective whole-cell current in patch clamp following removal
      of extracellular Na(+). Migration was quantified utilizing transwell chambers.
      AMPKalpha1 protein is expressed in ampk(+/+) DCs but not in ampk(-/-) DCs. CXCL12
      (300 ng/ml)-induced increase of [Ca(2+)](i), SOC entry, Orai 1 protein abundance,
      NCX, and NCKX were all significantly higher in ampk(-/-) DCs than in ampk(+/+)
      DCs. NCX and NCKX currents were similarly increased in ampk(-/-) DCs. Moreover,
      CXCL12 (50 ng/ml)-induced DC migration was enhanced in ampk(-/-) DCs. AMPK thus
      inhibits SOC entry, Na(+)/Ca(2+) exchangers, and migration of DCs.

PMID- 22474244
TI  - Secular trends in ischemic stroke characteristics in a rapidly developed country:
      results from the Korean Stroke Registry Study (secular trends in Korean stroke).
AB  - BACKGROUND: A dynamic change in industry, lifestyle, and healthcare structure
      brings a corresponding change in disease patterns. Limited data exist with
      respect to secular trends in stroke epidemiology in Korea, a rapidly developed
      country. METHODS AND RESULTS: We analyzed individual patient data registered the
      Korean Stroke Registry, a nationwide hospital-based stroke database, between
      January 2002 and November 2010. Mortality data were obtained from a national
      death certificate system. Linear or logistic regression analyses were performed
      to assess secular trends. A total of 46 098 patients were included in this study.
      Mean +/- SD age was 66.1 +/- 12.3 years, and 57.6% of the patients were men. Over
      the 9-year period, patient ages steadily increased by 0.24 year annually
      (P<0.001). Risk factor proportions of hypertension, diabetes, smoking, and prior
      stroke declined slightly (P<0.05 for all). However, dyslipidemia frequency showed
      a complex pattern of an initial decline and then an increase. For relative
      proportions of subtypes, cardioembolism increased, small vessel occlusion
      decreased, and large artery atherosclerosis remained stable. Still, intracranial
      stenosis overwhelms extracranial stenosis, but extracranial stenosis is on the
      rise. Arrival within 3 hours increased from 20% to 29%, and reperfusion therapy
      increased from 5.3% to 7.0%. Age-adjusted all-cause mortality did not decrease at
      30 days but decreased at 1 year over time. CONCLUSIONS: During the first decade
      of 21st century, stroke characteristics in Korea changed, likely because of
      increased lifespan, westernized lifestyle, and improved public awareness. Stroke
      experts need to cope with these distinguishing trends to establish a better
      strategy for prevention and acute therapy.

PMID- 22474245
TI  - High-density lipoprotein and mortality before age 90 in male physicians.
AB  - BACKGROUND: In cross-sectional and some cohort studies with shorter follow-up,
      high-density lipoprotein cholesterol (HDL-C) has been associated with longer
      life. We sought to examine the relationship between HDL-C and death before age 90
      in the Physicians' Health Study (PHS). METHODS AND RESULTS: Of PHS enrollees who
      had blood collected at PHS II baseline (approximately 1997), we selected 1351 men
      old enough to reach age 90 by March 4, 2009, and with complete data on HDL-C and
      total cholesterol, lifestyle factors, and comorbidities. We used Cox proportional
      hazards to determine the hazard ratios (HRs) and 95% confidence intervals (CIs)
      for all-cause, cardiovascular disease (CVD), and non-CVD mortality before age 90,
      adjusting for potential confounders. After a mean (SD) follow-up of 6.8 (3.2)
      years, 44.1% of men in the lowest baseline HDL-C quartile (<32.8 mg/dL) compared
      with 32.9% (11.2% absolute risk reduction) in the highest HDL-C quartile (>= 54.1
      mg/dL) died before age 90. In multivariable adjusted analyses, men in the highest
      HDL-C quartile had a 28% lower risk (HR, 0.72; 95% CI, 0.55 to 0.94) of death
      before age 90 compared with men in the lowest HDL-C quartile. In age-adjusted
      analyses, increasing baseline HDL-C was significantly associated with a lower
      risk of CVD death. No association was found between HDL-C and non-CVD mortality.
      CONCLUSION: In male physicians, higher baseline HDL-C levels were associated with
      a lower risk of all-cause and CVD mortality before age 90.

PMID- 22474246
TI  - Association of cardiorespiratory fitness with total, cardiovascular, and
      noncardiovascular mortality across 3 decades of follow-up in men and women.
AB  - BACKGROUND: The inverse, dose-dependent association between cardiorespiratory
      fitness and mortality is well-established; however, the pattern of the
      association between low fitness and mortality across short- (0 to 10 years),
      intermediate- (10 to 20 years), and long-term (>20 years) follow-up has not been
      studied. METHODS AND RESULTS: We included 46 575 men and 16 151 women (mean age
      44 years) from the Cooper Center Longitudinal Study. Participants were
      categorized as either "low fit" or "not low fit," based on age- and sex- adjusted
      treadmill times, and were followed for mortality, determined from the National
      Death Index. Multivariable-adjusted Cox proportional hazards models were
      constructed to compare the association between fitness and traditional risk
      factors, with mortality outcomes across short-, intermediate-, and long-term
      follow-up. After a median follow-up of 16 years, there were 1295 cardiovascular
      disease and 2840 noncardiovascular disease deaths. Low fitness was associated
      with all-cause mortality across all periods in men [0 to 10 years: hazard ratios
      (HR), 1.99 (95% confidence interval [CI], 1.66 to 2.40); 10 to 20 years: HR, 1.61
      (95% CI, 1.41 to 1.84); and >20 years: HR, 1.42 (95% CI, 1.27 to 1.60)] and in
      women [0 to 10 years: HR, 1.98 (95% CI, 1.27 to 3.10); 10 to 20 years: HR, 1.90
      (95% CI, 1.40 to 2.56); and >20 years: HR, 1.54 (95% CI, 1.15 to 2.07)]. Similar
      results were seen for both cardiovascular disease and noncardiovascular disease
      mortality. Although these associations were also consistent across most
      subgroups, low fitness appeared to be most strongly associated with mortality in
      the short term among individuals at highest short-term risk (ie, older age,
      abnormal exercise test). CONCLUSIONS: Similar to traditional risk factors,
      fitness is associated with mortality across short-, intermediate-, and long-term
      follow-up.

PMID- 22474247
TI  - A diet rich in unsaturated fatty acids prevents progression toward heart failure
      in a rabbit model of pressure and volume overload.
AB  - BACKGROUND: During heart failure (HF), cardiac metabolic substrate preference
      changes from fatty acid (FA) toward glucose oxidation. This change may cause
      progression toward heart failure. We hypothesize that a diet rich in FAs may
      prevent this process, and that dietary omega3-FAs have an added antiarrhythmic
      effect based on action potential (AP) shortening in animals with HF. METHODS AND
      RESULTS: Rabbits were fed a diet containing 1.25% (w/w) high oleic sunflower oil
      (HF-omega9, N=11), 1.25% fish oil (HF-omega3, N=11), or no supplement (HF
      control, N=8). Subsequently, HF was induced by volume and pressure overload.
      After 4 months, HF-parameters were assessed, electrocardiograms were recorded,
      and blood and ventricular tissue were collected. Myocytes were isolated for patch
      clamp or intracellular Ca(2+)- recordings to study electrophysiologic remodeling
      and arrhythmogenesis. Both the HF-omega9 and the HF-omega3 groups had larger
      myocardial FA oxidation capacity than HF control. The HF-omega3 group had
      significantly lower mean (+/- SEM) relative heart and lung weight (3.3+/-0.13 and
      3.2+/-0.12 g kg(-1), respectively) than HF control (4.8+/-0.30 and 4.5+/-0.23),
      and shorter QTc intervals (167+/-2.6 versus 182+/-6.4). The HF-omega9 also
      displayed a significantly reduced relative heart weight (3.6+/-0.26), but had
      similar QTc (179+/-4.3) compared with HF control. AP duration in the HF-omega3
      group was ~20% shorter due to increased I(to1) and I(K1) and triggered activity,
      and Ca(2+)-aftertransients were less than in the HF-omega9 group. CONCLUSIONS:
      Dietary unsaturated FAs started prior to induction of HF prevent hypertrophy and
      HF. In addition, fish oil FAs prevent HF-induced electrophysiologic remodeling
      and arrhythmias.

PMID- 22474248
TI  - C/EBPalpha and DEK coordinately regulate myeloid differentiation.
AB  - The transcription factor C/EBPalpha is a critical mediator of myeloid
      differentiation and is often functionally impaired in acute myeloid leukemia.
      Recent studies have suggested that oncogenic FLT3 activity disrupts wild-type
      C/EBPalpha function via phosphorylation on serine 21 (S21). Despite the apparent
      role of pS21 as a negative regulator of C/EBPalpha transcription activity, the
      mechanism by which phosphorylation tips the balance between transcriptionally
      competent and inhibited forms remains unresolved. In the present study, we used
      immuno-affinity purification combined with quantitative mass spectrometry to
      delineate the proteins associated with C/EBPalpha on chromatin. We identified
      DEK, a protein with genetic links to leukemia, as a member of the C/EBPalpha
      complexes, and demonstrate that this association is disrupted by S21
      phosphorylation. We confirmed that DEK is recruited specifically to chromatin
      with C/EBPalpha to enhance GCSFR3 promoter activation. In addition, we
      demonstrated that genetic depletion of DEK reduces the ability of C/EBPalpha to
      drive the expression of granulocytic target genes in vitro and disrupts G-CSF
      mediated granulocytic differentiation of fresh human BM-derived CD34(+) cells.
      Our data suggest that C/EBPalpha and DEK coordinately activate myeloid gene
      expression and that S21 phosphorylation on wild-type C/EBPalpha mediates protein
      interactions that regulate the differentiation capacity of hematopoietic
      progenitors.

PMID- 22474249
TI  - Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242
      cases included in the CryoVas survey.
AB  - Data on the clinical spectrum and therapeutic management of noninfectious mixed
      cryoglobulinemia vasculitis (CryoVas) in the era of hepatitis C virus screening
      are lacking. We analyzed data from 242 patients with noninfectious mixed CryoVas
      included in the French multicenter CryoVas survey. Baseline manifestations were
      purpura (75%), peripheral neuropathy (52%), arthralgia or arthritis (44%),
      glomerulonephritis (35%), cutaneous ulcers (16%), and cutaneous necrosis (14%). A
      connective tissue disease was diagnosed in 30% and B-cell non-Hodgkin lymphoma in
      22%, whereas the CryoVas was considered to be essential in 48%. With the use of
      Cox-marginal structural models, rituximab plus corticosteroids showed the greater
      therapeutic efficacy compared with corticosteroids alone and alkylating agents
      plus corticosteroids to achieve complete clinical, renal, and immunologic
      responses and a prednisone dosage < 10 mg/d at 6 months. However, this regimen
      was also associated with severe infections, particularly when high doses of
      corticosteroids were used, whereas death rates did not differ between the
      therapeutic regimens. The role of each of these strategies remains to be defined
      in well-designed randomized controlled trials.

PMID- 22474250
TI  - Activated expression of the chemokine Mig after chemotherapy contributes to
      chemotherapy-induced bone marrow suppression and lethal toxicity.
AB  - Alterations in gene expression after chemotherapy may potentially help to
      identify mediators that induce suppression or regeneration in bone marrow. This
      paper reports our observation that the expression of the chemokine monokine
      induced by IFN-gamma (Mig) and its receptor CXCR3 was significantly activated in
      mice after treatment with the chemotherapeutic agent 5-fluorouracil (5-FU). The
      neutralization of antibodies against the activated Mig increased the survival
      rate and accelerated BM recovery after chemotherapy. In addition, elevation of
      Mig plasma levels after 5-FU treatment corresponded with increased mortality. The
      cell cycle-inhibiting effect of the prophylactic administration of Mig protected
      hematopoietic progenitor cells (HPCs) from 1-beta-d-arabinofuranosylcytosine in
      spleen colony assays and enhanced the irradiated recipients' survival. In CXCR3(
      /-) mice, Mig did not propagate BM suppression, indicating that the suppressive
      effect of Mig is dependent on CXCR3. On the one hand, Mig stimulated p70 S6K and
      Erk1/2 pathways in mesenchymal stroma cells, inhibiting mesenchymal stroma cell
      dependent HPC expansion. Moreover, Mig suppressed the STAT5 pathway in HPCs,
      inhibiting leukocyte differentiation. Our results strongly suggest that Mig
      contributes to the acute lethal toxicity arising from 5-FU administration.
      Neutralization of Mig may offer new strategies to alleviate BM toxicity with
      potentially dramatic implications for chemotherapy.

PMID- 22474251
TI  - RhoH is critical for cell-microenvironment interactions in chronic lymphocytic
      leukemia in mice and humans.
AB  - Trafficking of B-cell chronic lymphocytic leukemia (CLL) cells to the bone marrow
      and interaction with supporting stromal cells mediates important survival and
      proliferation signals. Previous studies have demonstrated that deletion of Rhoh
      led to a delayed disease onset in a murine model of CLL. Here we assessed the
      impact of RhoH on homing, migration, and cell-contact dependent interactions of
      CLL cells. Rhoh(-/-) CLL cells exhibited reduced marrow homing and subsequent
      engraftment. In vitro migration toward the chemokines CXCL12 and CXCL13 and cell
      cell interactions between Rhoh(-/-) CLL cells and the supporting microenvironment
      was reduced. In the absence of RhoH the distribution of phosphorylated focal
      adhesion kinase, a protein known to coordinate activation of the Rho GTPases RhoA
      and Rac, appeared less polarized in chemokine-stimulated Rhoh(-/-) CLL cells, and
      activation and localization of RhoA and Rac was dysregulated leading to defective
      integrin function. These findings in the Rhoh(-/-) CLL cells were subsequently
      demonstrated to closely resemble changes in GTPase activation observed in human
      CLL samples after in vitro and in vivo treatment with lenalidomide, an agent with
      known influence on microenvironment protection, and suggest that RhoH plays a
      critical role in prosurvival CLL cell-cell and cell-microenvironment interactions
      with this agent.

PMID- 22474252
TI  - Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse
      vascular endothelium.
AB  - The importance of morphogenetic proteins (BMPs) and their antagonists in vascular
      development is increasingly being recognized. BMP-4 is essential for angiogenesis
      and is antagonized by matrix Gla protein (MGP) and crossveinless 2 (CV2), both
      induced by the activin receptor like-kinase 1 (ALK1) when stimulated by BMP-9. In
      this study, however, we show that CV2 preferentially binds and inhibits BMP-9
      thereby providing strong feedback inhibition for BMP-9/ALK1 signaling rather than
      for BMP-4/ALK2 signaling. CV2 disrupts complex formation involving ALK2, ALK1,
      BMP-4, and BMP-9 required for the induction of both BMP antagonists. It also
      limits VEGF expression, proliferation, and tube formation in ALK1-expressing
      endothelial cells. In vivo, CV2 deficiency translates into a dysregulation of
      vascular BMP signaling, resulting in an abnormal endothelium with increased
      endothelial cellularity and expression of lineage markers for mature endothelial
      cells. Thus, mutual regulation by BMP-9 and CV2 is essential in regulating the
      development of the vascular endothelium.

PMID- 22474253
TI  - Glycine normalizes hepatic triglyceride-rich VLDL secretion by triggering the CNS
      in high-fat fed rats.
AB  - RATIONALE: Dysregulation of hepatic triglyceride (TG)-rich very low-density
      lipoproteins (VLDL-TG) in obesity and type 2 diabetes contributes to the
      dyslipidemia that leads to cardiovascular morbidity. The central nervous system
      (CNS), particularly the hypothalamus, regulates hepatic lipid metabolism.
      Although the underlying neurocircuitry remains elusive, glycine has been
      documented to enhance CNS N-methyl-d-aspartate (NMDA) receptor-mediated
      transmission. OBJECTIVE: We tested the hypothesis that glycine regulates hepatic
      VLDL-TG secretion by potentiating NMDA receptor-mediated transmission in the CNS.
      METHODS AND RESULTS: Using 10-hour fasted male Sprague-Dawley rats implanted with
      stereotaxic cannulae into an extrahypothalamic region termed the dorsal vagal
      complex (DVC) and vascular catheters to enable direct DVC infusion and blood
      sampling, respectively, the rate of hepatic VLDL-TG secretion was measured
      following tyloxapol (an inhibitor of lipoprotein lipase) injection. Direct DVC
      infusion of glycine lowered VLDL-TG secretion, whereas NMDA receptor blocker MK
      801 fully negated glycine's effect. NR1 subunit of NMDA receptor antagonist 7
      chlorokynurenic acid, adenoviral injection of NR1 short hairpin RNA (shRNA), and
      hepatic vagotomy also nullified glycine's effect. Finally, DVC glycine normalized
      the hypersecretion of VLDL-TG induced by high-fat feeding. CONCLUSIONS: Molecular
      and pharmacological inhibition of the NR1-containing NMDA receptors in the DVC
      negated the ability of glycine to inhibit hepatic secretion of VLDL-TG in vivo.
      Importantly, the hypersecretion of VLDL-TG from the liver induced by a model of
      high-fat feeding was restored by the hepatic lipid control of CNS glycine
      sensing. These findings collectively suggest that glycine or glycine analogues
      may have therapeutic benefits in lowering plasma lipid levels in diabetes and
      obesity by triggering the CNS.

PMID- 22474254
TI  - Myeloid-specific Kruppel-like factor 2 inactivation increases macrophage and
      neutrophil adhesion and promotes atherosclerosis.
AB  - RATIONALE: Hemizygous deficiency of the transcription factor Kruppel-like factor
      2 (KLF2) has been shown previously to augment atherosclerosis in
      hypercholesterolemic mice. However, the cell type responsible for the increased
      atherosclerosis due to KLF2 deficiency has not been identified. This study
      examined the consequence of myeloid cell-specific KLF2 inactivation in
      atherosclerosis. METHODS AND RESULTS: Cell-specific knockout mice were generated
      by Cre/loxP recombination. Macrophages isolated from myeloid-specific Klf2
      knockout (myeKlf2(-/-)) mice were similar to myeKlf2(+/+) macrophages in response
      to activation, polarization, and lipid accumulation. However, in comparison to
      myeKlf2(+/+) macrophages, myeKlf2(-/-) macrophages adhered more robustly to
      endothelial cells. Neutrophils from myeKlf2(-/-) mice also adhered more robustly
      to endothelial cells, and fewer myeKlf2(-/-) neutrophils survived in culture over
      a 24-hour period in comparison with myeKlf2(+/+) neutrophils. When myeKlf2(-/-)
      mice were mated to Ldlr(-/-) mice and then fed a high fat and high cholesterol
      diet, significant increase in atherosclerosis was observed in the myeKlf2(-/
      )Ldlr(-/-) mice compared with myeKlf2(+/+)Ldlr(-/-) littermates. The increased
      atherosclerosis in myeKlf2(-/-)Ldlr(-/-) mice was associated with elevated
      presence of neutrophils and macrophages, with corresponding increase of
      myeloperoxidase as well as chlorinated and nitrosylated tyrosine epitopes in
      their lesion areas compared with myeKlf2(+/+)Ldlr(-/-) mice. CONCLUSIONS: This
      study documents a role for myeloid KLF2 expression in modulating atherosclerosis.
      The increased neutrophil accumulation and atherosclerosis progression with
      myeloid-specific KLF2 deficiency also underscores the importance of neutrophils
      in promoting vascular oxidative stress and atherosclerosis. Collectively, these
      results suggest that elevating KLF2 expression may be a novel strategy for
      prevention and treatment of atherosclerosis.

PMID- 22474255
TI  - Loss of angiotensin-converting enzyme-2 exacerbates diabetic cardiovascular
      complications and leads to systolic and vascular dysfunction: a critical role of
      the angiotensin II/AT1 receptor axis.
AB  - RATIONALE: Diabetic cardiovascular complications are reaching epidemic
      proportions. Angiotensin-converting enzyme-2 (ACE2) is a negative regulator of
      the renin-angiotensin system. We hypothesize that loss of ACE2 exacerbates
      cardiovascular complications induced by diabetes. OBJECTIVE: To define the role
      of ACE2 in diabetic cardiovascular complications. METHODS AND RESULTS: We used
      the well-validated Akita mice, a model of human diabetes, and generated double
      mutant mice using the ACE2 knockout (KO) mice (Akita/ACE2(-/y)). Diabetic state
      was associated with increased ACE2 in Akita mice, whereas additional loss of ACE2
      in these mice leads to increased plasma and tissue angiotensin II levels,
      resulting in systolic dysfunction on a background of impaired diastolic function.
      Downregulation of SERCA2 and lipotoxicity were equivalent in Akita and
      Akita/ACE2KO hearts and are likely mediators of the diastolic dysfunction.
      However, greater activation of protein kinase C and loss of Akt and endothelial
      nitric oxide synthase phosphorylation occurred in the Akita/ACE2KO hearts.
      Systolic dysfunction in Akita/ACE2KO mice was linked to enhanced activation of
      NADPH oxidase and metalloproteinases, resulting in greater oxidative stress and
      degradation of the extracellular matrix. Impaired flow-mediated dilation in vivo
      correlated with increased vascular oxidative stress in Akita/ACE2KO mice.
      Treatment with the AT1 receptor blocker, irbesartan rescued the systolic
      dysfunction, normalized altered signaling pathways, flow-mediated dilation, and
      the increased oxidative stress in the cardiovascular system. CONCLUSIONS: Loss of
      ACE2 disrupts the balance of the renin-angiotensin system in a diabetic state and
      leads to an angiotensin II/AT1 receptor-dependent systolic dysfunction and
      impaired vascular function. Our study demonstrates that ACE2 serves as a
      protective mechanism against diabetes-induced cardiovascular complications.

PMID- 22474256
TI  - Impact of changes in resuscitation practice on survival and neurological outcome
      after out-of-hospital cardiac arrest resulting from nonshockable arrhythmias.
AB  - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) claims millions of lives
      worldwide each year. OHCA survival from shockable arrhythmias (ventricular
      fibrillation/ tachycardia) improved in several communities after implementation
      of American Heart Association resuscitation guidelines that eliminated "stacked"
      shocks and emphasized chest compressions. "Nonshockable" rhythms are now the
      predominant presentation of OHCA; the benefit of such treatments on nonshockable
      rhythms is uncertain. METHODS AND RESULTS: We studied 3960 patients with
      nontraumatic OHCA from nonshockable initial rhythms treated by prehospital
      providers in King County, Washington, over a 10-year period. Outcomes during a 5
      year intervention period after adoption of new resuscitation guidelines were
      compared with the previous 5-year historical control period. The primary outcome
      was 1-year survival. Patient demographics and resuscitation characteristics were
      similar between the control (n=1774) and intervention (n=2186) groups, among whom
      471 of 1774 patients (27%) versus 742 of 2186 patients (34%), respectively,
      achieved return of spontaneous circulation; 82 (4.6%) versus 149 (6.8%) were
      discharged from hospital, 60 (3.4%) versus 112 (5.1%) with favorable neurological
      outcome; 73 (4.1%) versus 135 (6.2%) survived 1 month; and 48 (2.7%) versus 106
      patients (4.9%) survived 1 year (all P<=0.005). After adjustment for potential
      confounders, the intervention period was associated with an improved odds of 1.50
      (95% confidence interval, 1.29-1.74) for return of spontaneous circulation, 1.53
      (95% confidence interval, 1.14-2.05) for hospital survival, 1.56 (95% confidence
      interval, 1.11-2.18) for favorable neurological status, 1.54 (95% confidence
      interval, 1.14-2.10) for 1-month survival, and 1.85 (95% confidence interval,
      1.29-2.66) for 1-year survival. CONCLUSION: Outcomes from OHCA resulting from
      nonshockable rhythms, although poor by comparison with shockable rhythm
      presentations, improved significantly after implementation of resuscitation
      guideline changes, suggesting their potential to benefit all presentations of
      OHCA.

PMID- 22474257
TI  - Emerging roles for specific fatty acids in developmental processes.
AB  - Animals synthesize a vast range of fatty acids serving diverse cellular
      functions. The roles of specific fatty acids in early development are just
      beginning to be characterized. In the March 15, 2012, issue of Genes &
      Development, Kniazeva and colleagues (pp. 554-566) describe how the particular
      combination of a branched chain fatty acid and an acyl-CoA synthetase is required
      for critical cellular processes during early embryogenesis in Caenorhabditis
      elegans.

PMID- 22474258
TI  - Retrotransposon insertion targeting: a mechanism for homogenization of centromere
      sequences on nonhomologous chromosomes.
AB  - The centromeres of most eukaryotic organisms consist of highly repetitive arrays
      that are similar across nonhomologous chromosomes. These sequences evolve
      rapidly, thus posing a mystery as to how such arrays can be homogenized. Recent
      work in species in which centromere-enriched retrotransposons occur indicates
      that these elements preferentially insert into the centromeric regions. In two
      different Arabidopsis species, a related element was recognized in which the
      specificity for such targeting was altered. These observations provide a partial
      explanation for how homogenization of centromere DNA sequences occurs.

PMID- 22474259
TI  - Complexity in the signaling network: insights from the use of targeted inhibitors
      in cancer therapy.
AB  - Cancer often arises when normal cellular growth goes awry due to defects in
      critical signal transduction pathways. A growing number of inhibitors that target
      specific components of these pathways are in clinical use, but the success of
      these agents has been limited by the resistance to inhibitor therapy that
      ultimately develops. Studies have now shown that cancer cells respond to chronic
      drug treatment by adapting their signaling circuitry, taking advantage of pathway
      redundancy and routes of feedback and cross-talk to maintain their function. This
      review focuses on the compensatory signaling mechanisms highlighted by the use of
      targeted inhibitors in cancer therapy.

PMID- 22474260
TI  - Rev-erbalpha and Rev-erbbeta coordinately protect the circadian clock and normal
      metabolic function.
AB  - The nuclear receptor Rev-erbalpha regulates circadian rhythm and metabolism, but
      its effects are modest and it has been considered to be a secondary regulator of
      the cell-autonomous clock. Here we report that depletion of Rev-erbalpha together
      with closely related Rev-erbbeta has dramatic effects on the cell-autonomous
      clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were
      rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbbeta
      mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev
      erbalpha, and both Rev-erbs are recruited to a remarkably similar set of binding
      sites across the genome, enriched near metabolic genes. Depletion of both Rev
      erbs in liver synergistically derepresses several metabolic genes as well as
      genes that control the positive limb of the molecular clock. Moreover, deficiency
      of both Rev-erbs causes marked hepatic steatosis, in contrast to relatively
      subtle changes upon loss of either subtype alone. These findings establish the
      two Rev-erbs as major regulators of both clock function and metabolism,
      displaying a level of subtype collaboration that is unusual among nuclear
      receptors but common among core clock proteins, protecting the organism from
      major perturbations in circadian and metabolic physiology.

PMID- 22474261
TI  - Quantitative functions of Argonaute proteins in mammalian development.
AB  - Argonaute proteins (Ago1-4) are essential components of the microRNA-induced
      silencing complex and play important roles in both microRNA biogenesis and
      function. Although Ago2 is the only one with the slicer activity, it is not clear
      whether the slicer activity is a universally critical determinant for Ago2's
      function in mammals. Furthermore, functional specificities associated with
      different Argonautes remain elusive. Here we report that microRNAs are randomly
      sorted to individual Argonautes in mammals, independent of the slicer activity.
      When both Ago1 and Ago2, but not either Ago1 or Ago2 alone, are ablated in the
      skin, the global expression of microRNAs is significantly compromised and it
      causes severe defects in skin morphogenesis. Surprisingly, Ago3 is able to load
      microRNAs efficiently in the absence of Ago1 and Ago2, despite a significant loss
      of global microRNA expression. Quantitative analyses reveal that Ago2 interacts
      with a majority of microRNAs (60%) in the skin, compared with Ago1 (30%) and Ago3
      (<10%). This distribution is highly correlated with the abundance of each
      Argonaute, as quantified by shotgun proteomics. The quantitative correlation
      between Argonautes and their associated microRNAs is conserved in human cells.
      Finally, we measure the absolute expression of Argonaute proteins and determine
      that their copy number is ~1.4 * 10(5) to 1.7 * 10(5) molecules per cell.
      Together, our results reveal a quantitative picture for microRNA activity in
      mammals.

PMID- 22474263
TI  - Identifying risk factors for venous thromboembolism.

PMID- 22474262
TI  - Noncanonical repression of translation initiation through small RNA recruitment
      of the RNA chaperone Hfq.
AB  - The RNA chaperone Hfq is mostly known to help small regulatory RNAs (sRNAs)
      interact with target mRNAs to block initiating ribosomes. In this model, whereas
      the sRNA is directly competing with initiating 30S ribosomal subunits, Hfq plays
      only an indirect role, allowing optimal sRNA-mRNA pairing. Here we report that
      Hfq is recruited by a sRNA, Spot42, to bind to a precise AU-rich region in the
      vicinity of the translation initiation region (TIR) of sdhC mRNA and competes
      directly with 30S ribosomal subunits. We show that the sRNA Spot42 binds sdhC too
      far upstream of the TIR to directly repress translation initiation in vitro and
      in vivo. Contrary to the canonical model of sRNA regulation, this suggests a new
      mechanism where Hfq is directly involved in the translational repression of the
      target mRNA and where the sRNA acts only as a recruitment factor.

PMID- 22474265
TI  - Drug policy debate is needed.

PMID- 22474264
TI  - Triggers of hospitalization for venous thromboembolism.
AB  - BACKGROUND: The rate of hospitalization for venous thromboembolism (VTE) is
      increasing in the United States. Although predictors of hospital-acquired VTE are
      well-known, triggers of VTE before hospitalization are not as clearly defined.
      The objective of this study was to evaluate triggers of hospitalization for VTE.
      METHODS AND RESULTS: A case-crossover study was conducted. Subjects were
      participants in the Health and Retirement Study, a nationally representative
      sample of older Americans. Data were linked to Medicare files for hospital and
      nursing home stays, emergency department visits, outpatient visits including
      physician visits, and home health visits from years 1991 to 2007 (n=16 781). The
      outcome was hospitalization for venous thromboembolism (n=399). Exposures during
      the 90-day period before hospitalization for VTE were compared with exposures
      occurring in 4 comparison periods. Infection was the most common trigger of
      hospitalization for VTE, occurring in 52.4% of the risk periods before
      hospitalization. The adjusted incidence rate ratios (IRRs; 95% confidence
      interval) were 2.90 (2.13, 3.94) for all infection, 2.63 (1.90, 3.63) for
      infection without a previous hospital or skilled nursing facility stay, and 6.92
      (4.46, 10.72) for infection with a previous hospital or skilled nursing facility
      stay. Erythropoiesis-stimulating agents and blood transfusion were also
      associated with VTE hospitalization (IRR=9.33, 95% confidence interval: 1.19,
      73.42; IRR=2.57, 95% confidence interval: 1.17, 5.64; respectively). Other
      predictors included major surgeries, fractures (IRR=2.81), immobility (IRR=4.23),
      and chemotherapy (IRR=5.70). These predictors, combined, accounted for a large
      proportion (69.7%) of exposures before VTE hospitalization as opposed to 35.3% in
      the comparison periods. CONCLUSIONS: Risk prediction algorithms for VTE should be
      reevaluated to include infection, erythropoiesis-stimulating agents, and blood
      transfusion.

PMID- 22474266
TI  - Education, guidance, and equality are needed to address problem of antipsychotic
      prescribing in nursing homes.

PMID- 22474267
TI  - Dr Foster's correlation oversimplifies complicated and multifactorial problem.

PMID- 22474268
TI  - Use consultants only for critically ill patients at weekends.

PMID- 22474269
TI  - Remembering Karen Woo.

PMID- 22474270
TI  - Private partners have a different ethos from the NHS.

PMID- 22474271
TI  - Reform is a one way road.

PMID- 22474272
TI  - Instead of jumping up and down we must propose alternatives.

PMID- 22474273
TI  - Overseas health professionals should lobby their governments.

PMID- 22474274
TI  - Do not move player requiring resuscitation on field until return of spontaneous
      circulation.

PMID- 22474275
TI  - Improve environment to reduce pressure to prescribe antipsychotic drugs in
      nursing homes.

PMID- 22474276
TI  - Minimise sedentary behaviour at all ages for healthy ageing.

PMID- 22474277
TI  - Pressure to prescribe antipsychotic drugs in learning disability too.

PMID- 22474278
TI  - Interpret metanephrine results in light of clinical indications.

PMID- 22474279
TI  - US health reforms offer chance for primary care and public health to integrate,
      says report.

PMID- 22474280
TI  - Payments are to rise sixfold for teams that deliver good diabetes care for
      children.

PMID- 22474281
TI  - Fenretinide prevents lipid-induced insulin resistance by blocking ceramide
      biosynthesis.
AB  - Fenretinide is a synthetic retinoid that is being tested in clinical trials for
      the treatment of breast cancer and insulin resistance, but its mechanism of
      action has been elusive. Recent in vitro data indicate that fenretinide inhibits
      dihydroceramide desaturase, an enzyme involved in the biosynthesis of lipotoxic
      ceramides that antagonize insulin action. Because of this finding, we assessed
      whether fenretinide could improve insulin sensitivity and glucose homeostasis in
      vitro and in vivo by controlling ceramide production. The effect of fenretinide
      on insulin action and the cellular lipidome was assessed in a number of lipid
      challenged models including cultured myotubes and isolated muscles strips
      incubated with exogenous fatty acids and mice fed a high-fat diet. Insulin action
      was evaluated in the various models by measuring glucose uptake or disposal and
      the activation of Akt/PKB, a serine/threonine kinase that is obligate for insulin
      stimulated anabolism. The effects of fenretinide on cellular lipid levels were
      assessed by LC-MS/MS. Fenretinide negated lipid-induced insulin resistance in
      each of the model systems assayed. Simultaneously, the drug depleted cells of
      ceramide, while promoting the accumulation of the precursor dihydroceramide, a
      substrate for the reaction catalyzed by Des1. These data suggest that fenretinide
      improves insulin sensitivity, at least in part, by inhibiting Des1 and suggest
      that therapeutics targeting this enzyme may be a viable therapeutic means for
      normalizing glucose homeostasis in the overweight and diabetic.

PMID- 22474282
TI  - Cellular pregnenolone esterification by acyl-CoA:cholesterol acyltransferase.
AB  - Pregnenolone (PREG) can be converted to PREG esters (PE) by the plasma enzyme
      lecithin: cholesterol acyltransferase (LCAT), and by other enzyme(s) with unknown
      identity. Acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2) convert
      various sterols to steryl esters; their activities are activated by cholesterol.
      PREG is a sterol-like molecule, with 3-beta-hydroxy moiety at steroid ring A, but
      with much shorter side chain at steroid ring D. Here we show that without
      cholesterol, PREG is a poor ACAT substrate; with cholesterol, the V(max) for PREG
      esterification increases by 100-fold. The binding affinity of ACAT1 for PREG is
      30-50-fold stronger than that for cholesterol; however, PREG is only a substrate
      but not an activator, while cholesterol is both a substrate and an activator.
      These results indicate that the sterol substrate site in ACAT1 does not involve
      significant sterol-phospholipid interaction, while the sterol activator site
      does. Studies utilizing small molecule ACAT inhibitors show that ACAT plays a key
      role in PREG esterification in various cell types examined. Mice lacking ACAT1 or
      ACAT2 do not have decreased PREG ester contents in adrenals, nor do they have
      altered levels of the three major secreted adrenal steroids in serum. Mice
      lacking LCAT have decreased levels of PREG esters in the adrenals. These results
      suggest LCAT along with ACAT1/ACAT2 contribute to control pregnenolone ester
      content in different cell types and tissues.

PMID- 22474283
TI  - FK506 binding protein 8 peptidylprolyl isomerase activity manages a late stage of
      cystic fibrosis transmembrane conductance regulator (CFTR) folding and stability.
AB  - Cystic fibrosis (CF) is caused by mutations in the apical chloride channel cystic
      fibrosis transmembrane conductance regulator (CFTR) with 90% of patients carrying
      at least one deletion of the F508 (DeltaF508) allele. This mutant form of CFTR is
      characterized by a folding and trafficking defect that prevents exit from the
      endoplasmic reticulum. We previously reported that DeltaF508 CFTR can be
      recovered in a complex with Hsp90 and its co-chaperones as an on-pathway folding
      intermediate, suggesting that Delta508 CF disease arises due to a failure of the
      proteostasis network (PN), which manages protein folding and degradation in the
      cell. We have now examined the role of FK506-binding protein 8 (FKBP8), a
      component of the CFTR interactome, during the biogenesis of wild-type and
      DeltaF508 CFTR. FKBP8 is a member of the peptidylprolyl isomerase family that
      mediates the cis/trans interconversion of peptidyl prolyl bonds. Our results
      suggest that FKBP8 is a key PN factor required at a post-Hsp90 step in CFTR
      biogenesis. In addition, changes in its expression level or alteration of its
      activity by a peptidylprolyl isomerase inhibitor alter CFTR stability and
      transport. We propose that CF is caused by the sequential failure of the
      prevailing PN pathway to stabilize DeltaF508-CFTR for endoplasmic reticulum
      export, a pathway that can be therapeutically managed.

PMID- 22474284
TI  - ATP synthesis-coupled and -uncoupled acetate production from acetyl-CoA by
      mitochondrial acetate:succinate CoA-transferase and acetyl-CoA thioesterase in
      Trypanosoma.
AB  - Insect stage trypanosomes use an "acetate shuttle" to transfer mitochondrial
      acetyl-CoA to the cytosol for the essential fatty acid biosynthesis. The
      mitochondrial acetate sources are acetate:succinate CoA-transferase (ASCT) and an
      unknown enzymatic activity. We have identified a gene encoding acetyl-CoA
      thioesterase (ACH) activity, which is shown to be the second acetate source.
      First, RNAi-mediated repression of ASCT in the ACH null background abolishes
      acetate production from glucose, as opposed to both single ASCT and ACH mutants.
      Second, incorporation of radiolabeled glucose into fatty acids is also abolished
      in this ACH/ASCT double mutant. ASCT is involved in ATP production, whereas ACH
      is not, because the ASCT null mutant is ~1000 times more sensitive to oligomycin,
      a specific inhibitor of the mitochondrial F(0)/F(1)-ATP synthase, than wild-type
      cells or the ACH null mutant. This was confirmed by RNAi repression of the
      F(0)/F(1)-ATP synthase F(1)beta subunit, which is lethal when performed in the
      ASCT null background but not in the wild-type cells or the ACH null background.
      We concluded that acetate is produced from both ASCT and ACH; however, only ASCT
      is responsible, together with the F(0)/F(1)-ATP synthase, for ATP production in
      the mitochondrion.

PMID- 22474285
TI  - Hedgehog secretion and signal transduction in vertebrates.
AB  - Signaling by the Hedgehog (Hh) family of secreted proteins is essential for
      proper embryonic patterning and development. Dysregulation of Hh signaling is
      associated with a variety of human diseases ranging from developmental disorders
      such as holoprosencephaly to certain forms of cancer, including medulloblastoma
      and basal cell carcinoma. Genetic studies in flies and mice have shaped our
      understanding of Hh signaling and revealed that nearly all core components of the
      pathway are highly conserved. Although many aspects of the Drosophila Hh pathway
      are conserved in vertebrates, mechanistic differences between the two species
      have begun to emerge. Perhaps the most striking divergence in vertebrate Hh
      signaling is its dependence on the primary cilium, a vestigial organelle that is
      largely absent in flies. This minireview will provide an overview of Hh signaling
      and present recent insights into vertebrate Hh secretion, receptor binding, and
      signal transduction.

PMID- 22474286
TI  - Forkhead transcription factor FOXO3a protein activates nuclear factor kappaB
      through B-cell lymphoma/leukemia 10 (BCL10) protein and promotes tumor cell
      survival in serum deprivation.
AB  - FOXO3a, a member of the Forkhead box O (FoxO) transcription factor family, is
      believed to be a tumor suppressor because it was found that FOXO3a inactivation
      promoted cell transformation and tumor progression. There are also a few studies
      showing that FOXO3a protected cells under stress conditions, including oxidative
      stress, serum deprivation, and hypoxia. It was reported that FOXO3a promoted
      invasion of cancer cells. Thus, the role of FOXO3a in cancer is complicated.
      Here, we report that FOXO3a is a positive regulator of nuclear factor kappaB (NF
      kappaB) signaling. We found that overexpression of FOXO3a increased and knockdown
      of FOXO3a repressed NF-kappaB activities. Mechanistic studies indicate that
      FOXO3a activated NF-kappaB via inducing expression of B-cell lymphoma/leukemia 10
      (BCL10), an upstream regulator of IkappaB kinase (IKK)/NF-kappaB signaling. We
      found that the serum deprivation activated NF-kappaB, which was blocked by
      inhibition of FOXO3a. Knockdown of FOXO3a enhanced cell apoptosis under serum
      free conditions, which was inhibited by overexpression of BCL10. These results
      suggest that FOXO3a promotes cell survival via BCL10/NF-kappaB in serum
      starvation. Our findings may add another layer to the complexity of the role of
      FOXO3a in cancer. Therefore, caution should be taken when FOXO3a is employed as a
      target for cancer therapy.

PMID- 22474288
TI  - Smurf1 protein negatively regulates interferon-gamma signaling through promoting
      STAT1 protein ubiquitination and degradation.
AB  - Interferons are important cytokines that mediate antiviral, antiproliferative,
      antitumor, and immunoregulatory activities. However, uncontrolled IFN signaling
      may lead to autoimmune diseases. Here we identified Smurf1 as a negative
      regulator for IFN-gamma signaling by targeting STAT1 for ubiquitination and
      proteasomal degradation. Smurf1 interacted with STAT1 through the WW domains of
      Smurf1 and the PY motif in STAT1 and catalyzed K48-linked polyubiquitination of
      STAT1. Interestingly, the Smurf1-mediated ubiquitination and degradation did not
      require STAT1 tyrosine and serine phosphorylation. Subsequently, overexpression
      of Smurf1 attenuated IFN-gamma-mediated STAT1 activation and antiviral immune
      responses, whereas knockdown of Smurf1 enhanced IFN-gamma-mediated STAT1
      activation, expression of STAT1 target genes, and antiviral immune responses.
      Furthermore, IFN-gamma stimulation led to enhanced expression of Smurf1.
      Therefore, our results demonstrate that Smurf1 is a negative feedback regulator
      for IFN-gamma signaling by targeting STAT1 for ubiquitination and proteasomal
      degradation.

PMID- 22474287
TI  - Structure-activity analysis of niclosamide reveals potential role for cytoplasmic
      pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling.
AB  - Mammalian target of rapamycin complex 1 (mTORC1) signaling is frequently
      dysregulated in cancer. Inhibition of mTORC1 is thus regarded as a promising
      strategy in the treatment of tumors with elevated mTORC1 activity. We have
      recently identified niclosamide (a Food and Drug Administration-approved
      antihelminthic drug) as an inhibitor of mTORC1 signaling. In the present study,
      we explored possible mechanisms by which niclosamide may inhibit mTORC1
      signaling. We tested whether niclosamide interferes with signaling cascades
      upstream of mTORC1, the catalytic activity of mTOR, or mTORC1 assembly. We found
      that niclosamide does not impair PI3K/Akt signaling, nor does it inhibit mTORC1
      kinase activity. We also found that niclosamide does not interfere with mTORC1
      assembly. Previous studies in helminths suggest that niclosamide disrupts pH
      homeostasis of the parasite. This prompted us to investigate whether niclosamide
      affects the pH balance of cancer cells. Experiments in both breast cancer cells
      and cell-free systems demonstrated that niclosamide possesses protonophoric
      activity in cells and in vitro. In cells, niclosamide dissipated protons (down
      their concentration gradient) from lysosomes to the cytosol, effectively lowering
      cytoplasmic pH. Notably, analysis of five niclosamide analogs revealed that the
      structural features of niclosamide required for protonophoric activity are also
      essential for mTORC1 inhibition. Furthermore, lowering cytoplasmic pH by means
      other than niclosamide treatment (e.g. incubation with propionic acid or
      bicarbonate withdrawal) recapitulated the inhibitory effects of niclosamide on
      mTORC1 signaling, lending support to a possible role for cytoplasmic pH in the
      control of mTORC1. Our data illustrate a potential mechanism for chemical
      inhibition of mTORC1 signaling involving modulation of cytoplasmic pH.

PMID- 22474289
TI  - Electron transfer in subunit NuoI (TYKY) of Escherichia coli NADH:quinone
      oxidoreductase (NDH-1).
AB  - Bacterial proton-translocating NADH:quinone oxidoreductase (NDH-1) consists of a
      peripheral and a membrane domain. The peripheral domain catalyzes the electron
      transfer from NADH to quinone through a chain of seven iron-sulfur (Fe/S)
      clusters. Subunit NuoI in the peripheral domain contains two [4Fe-4S] clusters
      (N6a and N6b) and plays a role in bridging the electron transfer from cluster N5
      to the terminal cluster N2. We constructed mutants for eight individual Cys
      coordinating Fe/S clusters. With the exception of C63S, all mutants had damaged
      architecture of NDH-1, suggesting that Cys-coordinating Fe/S clusters help
      maintain the NDH-1 structure. Studies of three mutants (C63S-coordinating N6a,
      P110A located near N6a, and P71A in the vicinity of N6b) were carried out using
      EPR measurement. These three mutations did not affect the EPR signals from [2Fe
      2S] clusters and retained electron transfer activities. Signals at g(z) = 2.09
      disappeared in C63S and P110A but not in P71A. Considering our data together with
      the available information, g(z,x) = 2.09, 1.88 signals are assigned to cluster
      N6a. It is of interest that, in terms of g(z,x) values, cluster N6a is similar to
      cluster N4. In addition, we investigated the residues (Ile-94 and Ile-100) that
      are predicted to serve as electron wires between N6a and N6b and between N6b and
      N2, respectively. Replacement of Ile-100 and Ile-94 with Ala/Gly did not affect
      the electron transfer activity significantly. It is concluded that conserved Ile
      100 and Ile-94 are not essential for the electron transfer.

PMID- 22474290
TI  - Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): role of
      stromal androgen receptor in macrophage-induced prostate stromal cell
      proliferation.
AB  - Infiltrated macrophages may play important roles in the development and
      progression of benign prostatic hyperplasia (BPH), but the underlying mechanisms
      remain largely unknown. We found increased macrophages infiltration in human and
      mouse BPH tissues. By establishing a co-culture transwell system, we found
      increased migration of macrophages and proliferation of prostate stromal cells
      during co-culture. Importantly, stromal androgen receptor (AR) could enhance the
      migration of macrophages and macrophage-mediated stromal cell proliferation. We
      identified CCL3 as an AR downstream player, and found CCL3 levels were notably
      increased in human and mouse BPH prostates. Ablation of prostate stromal AR in a
      mouse BPH model significantly reduced CCL3 expression levels in prostates.
      Consistently, targeting AR via an AR degradation enhancer, ASC-J9(r), or
      neutralization of CCL3 with an antibody, resulted in suppression of macrophage
      migration and prostate stromal cell growth. Our study provides mechanistic
      insights on the regulation of prostate stromal cells by macrophages via stromal
      AR/CCL3 signaling pathways, which could potentially allow the development of
      therapeutic approaches for battling BPH with persistent inflammation.

PMID- 22474291
TI  - Identification of the Bombyx red egg gene reveals involvement of a novel
      transporter family gene in late steps of the insect ommochrome biosynthesis
      pathway.
AB  - Ommochromes are one of the major pigments involved in coloration of eggs, eyes,
      and body surface of insects. However, the molecular mechanisms of the final steps
      of ommochrome pigment synthesis have been largely unknown. The eggs of the
      silkworm Bombyx mori contain a mixture of ommochrome pigments, and exhibit a
      brownish lilac color. The recessive homozygous of egg and eye color mutant, red
      egg (re), whose eggs display a pale orange color instead of normal dark
      coloration, has been long suggested to have a defect in the biosynthesis of the
      final ommochrome pigments. Here, we identify the gene responsible for the re
      locus by positional cloning, mutant analysis, and RNAi experiments. In the re
      mutants, we found that a 541-bp transposable element is inserted into the ORF of
      BGIBMGA003497-1 (Bm-re) encoding a novel member of a major facilitator
      superfamily transporter, causing disruption of the splicing of exon 9, resulting
      in two aberrant transcripts with frameshifts yielding nonfunctional proteins
      lacking the C-terminal transmembrane domains. Bm-re function in pigmentation was
      confirmed by embryonic RNAi experiments. Homologs of the Bm-re gene were found in
      all insect genomes sequenced at present, except for 12 sequenced Drosophila
      genomes, which seemed to correlate with the previous studies that have
      demonstrated that eye ommochrome composition is different from other insects in
      several Dipterans. Knockdown of the Bm-re homolog by RNAi in the red flour beetle
      Tribolium castaneum caused adult compound eye coloration defects, indicating a
      conserved role in ommochrome pigment biosynthesis at least among holometabolous
      insects.

PMID- 22474292
TI  - Scleraxis modulates bone morphogenetic protein 4 (BMP4)-Smad1 protein-smooth
      muscle alpha-actin (SMA) signal transduction in diabetic nephropathy.
AB  - Activation of mesangial cells (MCs), which is characterized by induction of
      smooth muscle alpha-actin (SMA) expression, contributes to a key event in various
      renal diseases; however, the mechanisms controlling MC differentiation are still
      largely undefined. Activated Smad1 induced SMA in a dose-dependent manner in MCs.
      As a direct regulating molecule for SMA, we identified and characterized
      scleraxis (Scx) as a new phenotype modulator in advanced glycation end product
      (AGE)-exposed MCs. Scx physically associated with E12 and bound the E-box in the
      promoter of SMA and negatively regulated the AGE-induced SMA expression. Scx
      induced expression and secretion of bone morphogenetic protein 4 (BMP4), thereby
      controlling the Smad1 activation in AGE-treated MCs. In diabetic mice, Scx was
      concomitantly expressed with SMA in the glomeruli. Inhibitor of differentiation 1
      (Id1) was further induced by extended treatment with AGE, thereby dislodging Scx
      from the SMA promoter. These data suggest that Scx and Id1 are involved in the
      BMP4-Smad1-SMA signal transduction pathway besides the TGFbeta1-Smad1-SMA
      signaling pathway and modulate phenotypic changes in MCs in diabetic nephropathy.

PMID- 22474293
TI  - MicroRNAs are essential for stretch-induced vascular smooth muscle contractile
      differentiation via microRNA (miR)-145-dependent expression of L-type calcium
      channels.
AB  - Stretch of the vascular wall is an important stimulus to maintain smooth muscle
      contractile differentiation that is known to depend on L-type calcium influx, Rho
      activation, and actin polymerization. The role of microRNAs in this response was
      investigated using tamoxifen-inducible and smooth muscle-specific Dicer KO mice.
      In the absence of Dicer, which is required for microRNA maturation, smooth muscle
      microRNAs were completely ablated. Stretch-induced contractile differentiation
      and Rho-dependent cofilin-2 phosphorylation were dramatically reduced in Dicer KO
      vessels. On the other hand, acute stretch-sensitive growth signaling, which is
      independent of influx through L-type calcium channels, was not affected by Dicer
      KO. Contractile differentiation induced by the actin polymerizing agent
      jasplakinolide was not altered by deletion of Dicer, suggesting an effect
      upstream of actin polymerization. Basal and stretch-induced L-type calcium
      channel expressions were both decreased in Dicer KO portal veins, and inhibition
      of L-type channels in control vessels mimicked the effects of Dicer deletion.
      Furthermore, inhibition of miR-145, a highly expressed microRNA in smooth muscle,
      resulted in a similar reduction of L-type calcium channel expression. This was
      abolished by the Ca(2+)/calmodulin-dependent protein kinase II inhibitor KN93,
      suggesting that Ca(2+)/calmodulin-dependent protein kinase IIdelta, a target of
      miR-145 and up-regulated in Dicer KO, plays a role in the regulation of L-type
      channel expression. These results show that microRNAs play a crucial role in
      stretch-induced contractile differentiation in the vascular wall in part via miR
      145-dependent regulation of L-type calcium channels.

PMID- 22474294
TI  - Two chimeric regulators of G-protein signaling (RGS) proteins differentially
      modulate soybean heterotrimeric G-protein cycle.
AB  - Heterotrimeric G-proteins and the regulator of G-protein signaling (RGS)
      proteins, which accelerate the inherent GTPase activity of Galpha proteins, are
      common in animals and encoded by large gene families; however, in plants G
      protein signaling is thought to be more limited in scope. For example,
      Arabidopsis thaliana contains one Galpha, one Gbeta, three Ggamma, and one RGS
      protein. Recent examination of the Glycine max (soybean) genome reveals a larger
      set of G-protein-related genes and raises the possibility of more intricate G
      protein networks than previously observed in plants. Stopped-flow analysis of GTP
      binding and GDP/GTP exchange for the four soybean Galpha proteins (GmGalpha1-4)
      reveals differences in their kinetic properties. The soybean genome encodes two
      chimeric RGS proteins with an N-terminal seven transmembrane domain and a C
      terminal RGS box. Both GmRGS interact with each of the four GmGalpha and regulate
      their GTPase activity. The GTPase-accelerating activities of GmRGS1 and -2 differ
      for each GmGalpha, suggesting more than one possible rate of the G-protein cycle
      initiated by each of the Galpha proteins. The differential effects of GmRGS1 and
      GmRGS2 on GmGalpha1-4 result from a single valine versus alanine difference. The
      emerging picture suggests complex regulation of the G-protein cycle in soybean
      and in other plants with expanded G-protein networks.

PMID- 22474295
TI  - Enoxacin directly inhibits osteoclastogenesis without inducing apoptosis.
AB  - Enoxacin has been identified as a small molecule inhibitor of binding between the
      B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone
      resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that
      enoxacin acts directly and specifically on osteoclasts by disrupting the
      interaction between plasma membrane-directed V-ATPases, which contain the
      osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with
      this hypothesis, enoxacin dose-dependently reduced the number of multinuclear
      cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by
      RANK-L-stimulated osteoclast precursors. Enoxacin (50 MUM) did not induce
      apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3
      subunit, but not the "housekeeping" a1-subunit, were isolated bound to actin.
      Treatment with enoxacin reduced the association of V-ATPase subunits with the
      detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin
      triggered significant reductions in several osteoclast-selective mRNAs, but
      levels of various osteoclast proteins were not reduced, as determined by
      quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots
      demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein L
      plastin was altered in cells treated with 50 MUM enoxacin. Flow cytometry
      revealed that enoxacin treatment favored the expression of high levels of DC
      STAMP on the surface of osteoclasts. Our data show that enoxacin directly
      inhibits osteoclast formation without affecting cell viability by a novel
      mechanism that involves changes in posttranslational processing and trafficking
      of several proteins with known roles in osteoclast function. We propose that
      these effects are downstream to blocking the binding interaction between a3
      containing V-ATPases and microfilaments.

PMID- 22474296
TI  - Structural snapshots of yeast alkyl hydroperoxide reductase Ahp1 peroxiredoxin
      reveal a novel two-cysteine mechanism of electron transfer to eliminate reactive
      oxygen species.
AB  - Peroxiredoxins (Prxs) are thiol-specific antioxidant proteins that protect cells
      against reactive oxygen species and are involved in cellular signaling pathways.
      Alkyl hydroperoxide reductase Ahp1 belongs to the Prx5 subfamily and is a two
      cysteine (2-Cys) Prx that forms an intermolecular disulfide bond. Enzymatic
      assays and bioinformatics enabled us to re-assign the peroxidatic cysteine (C(P))
      to Cys-62 and the resolving cysteine (C(R)) to Cys-31 but not the previously
      reported Cys-120. Thus Ahp1 represents the first 2-Cys Prx with a peroxidatic
      cysteine after the resolving cysteine in the primary sequence. We also found the
      positive cooperativity of the substrate t-butyl hydroperoxide binding to Ahp1
      homodimer at a Hill coefficient of ~2, which enabled Ahp1 to eliminate
      hydroperoxide at much higher efficiency. To gain the structural insights into the
      catalytic cycle of Ahp1, we determined the crystal structures of Ahp1 in the
      oxidized, reduced, and Trx2-complexed forms at 2.40, 2.91, and 2.10 A resolution,
      respectively. Structural superposition of the oxidized to the reduced form
      revealed significant conformational changes at the segments containing C(P) and
      C(R). An intermolecular C(P)-C(R) disulfide bond crossing the A-type dimer
      interface distinguishes Ahp1 from other typical 2-Cys Prxs. The structure of the
      Ahp1-Trx2 complex showed for the first time how the electron transfers from
      thioredoxin to a peroxidase with a thioredoxin-like fold. In addition, site
      directed mutagenesis in combination with enzymatic assays suggested that the
      peroxidase activity of Ahp1 would be altered upon the urmylation (covalently
      conjugated to ubiquitin-related modifier Urm1) of Lys-32.

PMID- 22474297
TI  - Resolving nitrogen-15 and proton chemical shifts for mobile segments of elastin
      with two-dimensional NMR spectroscopy.
AB  - In this study, one- and two-dimensional NMR experiments are applied to uniformly
      (15)N-enriched synthetic elastin, a recombinant human tropoelastin that has been
      cross-linked to form an elastic hydrogel. Hydrated elastin is characterized by
      large segments that undergo "liquid-like" motions that limit the efficiency of
      cross-polarization. The refocused insensitive nuclei enhanced by polarization
      transfer experiment is used to target these extensive, mobile regions of this
      protein. Numerous peaks are detected in the backbone amide region of the protein,
      and their chemical shifts indicate the completely unstructured, "random coil"
      model for elastin is unlikely. Instead, more evidence is gathered that supports a
      characteristic ensemble of conformations in this rubber-like protein.

PMID- 22474298
TI  - Amantadine: the journey from fighting flu to treating Parkinson disease.
AB  - OBJECTIVE: To explore how amantadine transitioned from an anti-flu drug to
      antiparkinsonian agent. METHODS: A review of the historical literature on the use
      of amantadine from 1966 to the present was performed. RESULTS: Amantadine was
      originally introduced and utilized as an antiviral medication. A single patient
      noticed relief in her Parkinson disease (PD) symptoms after taking amantadine for
      a flu infection, and this observation sparked an interest, and several important
      studies that eventually led to a new drug indication. CONCLUSION: Amantadine has
      over the years fallen out of favor as a drug to address influenza infection;
      however, it has become part of the arsenal utilized for early symptomatic
      treatment of PD, as well an option for treating dyskinesia.

PMID- 22474299
TI  - Noteworthy orbital-craniocerebral trauma.

PMID- 22474301
TI  - Clinical reasoning: a middle-aged woman with progressive symmetric weakness and a
      CSF pleocytosis.

PMID- 22474302
TI  - Teaching neuroimages: brain MRI aspects of isolated cerebral mucormycosis.

PMID- 22474303
TI  - Sequence discrimination by DNA-binding domain of ETS family transcription factor
      PU.1 is linked to specific hydration of protein-DNA interface.
AB  - PU.1 is an essential transcription factor in normal hematopoietic lineage
      development. It recognizes a large number of promoter sites differing only in
      bases flanking a core consensus of 5'-GGAA-3'. DNA binding is mediated by its ETS
      domain, whose sequence selectivity directly corresponds to the transactivational
      activity and frequency of binding sites for full-length PU.1 in vivo. To better
      understand the basis of sequence discrimination, we characterized its binding
      properties to a high affinity and low affinity site. Despite sharing a homologous
      structural framework as confirmed by DNase I and hydroxyl radical footprinting,
      the two complexes exhibit striking heterogeneity in terms of hydration
      properties. High affinity binding is destabilized by osmotic stress, whereas low
      affinity binding is insensitive. Dimethyl sulfate footprinting showed that the
      major groove at the core consensus is protected in the high affinity complex but
      accessible in the low affinity one. Finally, destabilization of low affinity
      binding by salt is in quantitative agreement with the number of phosphate
      contacts but is substantially attenuated in high affinity binding. These
      observations support a mechanism of sequence discrimination wherein specifically
      bound water molecules couple flanking backbone contacts with base-specific
      interactions in a sequestered cavity at the core consensus. The implications of
      this model with respect to other ETS paralogs are discussed.

PMID- 22474304
TI  - Polio eradication: a complex end game.

PMID- 22474305
TI  - US Supreme Court hears arguments against health reform act.

PMID- 22474306
TI  - Mortality falls if consultants work blocks of days rather than single day rotas,
      survey finds.

PMID- 22474307
TI  - Collaboration with drug industry won't affect clinical decisions, says new guide.

PMID- 22474308
TI  - Journals question integrity of almost 200 papers by Japanese anaesthetist.

PMID- 22474309
TI  - BMA to ballot on industrial action over pensions in May.

PMID- 22474310
TI  - Descending aortic blood flow during aortic cross-clamp indicates postoperative
      splanchnic perfusion and gastrointestinal function in patients undergoing aortic
      reconstruction.
AB  - BACKGROUND: The purpose of this observational study was to investigate the
      relationship between splanchnic and renal blood flow during infrarenal aortic
      cross-clamp (XC) and postoperative gastrointestinal perfusion and function.
      METHODS: Descending aortic blood flow (DABF) was continuously monitored with an
      oesophageal Doppler monitor (Cardio-Q, Deltex Ltd, Chichester, UK) in 31 patients
      undergoing elective abdominal aortic aneurysm repair. Cardiac output (CO) was
      determined by indocyanine green dilution before, during, and after XC.
      Perioperative gastrointestinal perfusion was assessed by gastric intramucosal pH
      (pHi, Tonocap, GE Healthcare, Helsinki, Finland). Postoperative gastrointestinal
      recovery was assessed by the number of postoperative days until the patient
      successfully resumed solid food intake. The relationship between the mean DABF
      during XC and gastric pHi after XC release and postoperative gastrointestinal
      recovery was analysed with Spearman's correlation coefficient. RESULTS: accounted
      for ~ 55% of CO during XC and significantly decreased during XC, despite arterial
      pressure remaining within an optimal range. There were two distinct relationships
      between DABF during XC and gastric pHi after XC release. Gastric pHi steeply and
      linearly declined when indexed DABF was below 0.82 litre min(-1) m(-2). Above
      this critical value, there was no linear relationship between them. The duration
      of postoperative gastrointestinal dysfunction was inversely correlated with the
      mean DABF during XC. The best cut-off value of the mean indexed DABF during XC to
      prevent prolonged gastrointestinal dysfunction was 1.2 litre min(-1) m(-2).
      CONCLUSIONS: Decreased DABF during XC associates splanchnic hypoperfusion after
      XC release and delayed recovery of gastrointestinal function.

PMID- 22474312
TI  - Medical therapy for the patient with obesity.

PMID- 22474311
TI  - Clinical and genetic determinants of torsade de pointes risk.

PMID- 22474313
TI  - Cerebral venous thrombosis.

PMID- 22474314
TI  - Spontaneous left atrial hematoma mimicking an acute aortic syndrome: the utility
      of high-resolution computed tomography.

PMID- 22474315
TI  - Anomalous vena caval return to the left atrium.

PMID- 22474317
TI  - Letter from van Galen et al regarding article, "Cardiac amyloidosis: a treatable
      disease often overlooked".

PMID- 22474318
TI  - Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis.
AB  - The BCR-ABL1-negative myeloproliferative neoplasms (e.g., essential
      thrombocythemia, polycythemia vera, and primary myelofibrosis) are a group of
      heterogeneous hematologic malignancies that involve a clonal proliferation of
      hematopoietic stem cells. Thrombosis, bleeding, and transformation to acute
      leukemia reduce the overall survival of patients with myelofibrosis, a disease
      typified by progressive splenomegaly and disease-related symptoms such as
      fatigue, pruritus, and bony pains. Hematopoietic stem cell transplant offers the
      only potential for cure in a minority of eligible patients, leaving a serious
      unmet need for improved therapies. Recent advances in our understanding of the
      pathogenetic mechanisms underlying these diseases have led to an explosion of
      clinical trials evaluating novel therapies. The discovery of an activating
      mutation in the Janus-activated kinase 2 (JAK2) gene provided a therapeutic
      target to downregulate this activated signaling pathway, which influences the
      phenotype of these diseases. Ruxolitinib (Jakafi; Incyte) is a small-molecule
      inhibitor of JAK1/2 that has proved to be effective at reducing splenomegaly and
      ameliorating symptoms in myeloproliferative neoplasms. Based on the results of 2
      pivotal randomized phase III clinical trials, ruxolitinib has become the first
      therapeutic to be approved by the U.S. Food and Drug Administration for treatment
      of patients with myelofibrosis. Ruxolitinib offers a well-tolerated oral
      therapeutic option for patients with myelofibrosis with symptomatic splenomegaly
      and debilitating disease-related symptoms, but it does not seem to be effective
      at eliminating the underlying hematological malignancy.

PMID- 22474319
TI  - Molecular pathways: vasculogenic mimicry in tumor cells: diagnostic and
      therapeutic implications.
AB  - Tumor cell vasculogenic mimicry (VM) describes the functional plasticity of
      aggressive cancer cells forming de novo vascular networks, thereby providing a
      perfusion pathway for rapidly growing tumors, transporting fluid from leaky
      vessels, and/or connecting with endothelial-lined vasculature. The underlying
      induction of VM seems to be related to hypoxia, which may also promote the
      plastic, transendothelial phenotype of tumor cells capable of VM. Since its
      introduction in 1999 as a novel paradigm for melanoma tumor perfusion, many
      studies have contributed new insights into the underlying molecular pathways
      supporting VM in a variety of tumors, including melanoma, glioblastoma,
      carcinomas, and sarcomas. In particular, critical VM-modulating genes are
      associated with vascular (VE-cadherin, EphA2, VEGF receptor 1), embryonic and/or
      stem cell (Nodal, Notch4), and hypoxia-related (hypoxia-inducible factor, Twist1)
      signaling pathways. Each of these pathways warrants serious scrutiny as potential
      therapeutic, vascular targets, and diagnostic indicators of plasticity, drug
      resistance, and the aggressive metastatic phenotype.

PMID- 22474320
TI  - Intracellular nitric oxide mediates neuroproliferative effect of neuropeptide y
      on postnatal hippocampal precursor cells.
AB  - Neuropeptide Y (NPY) is widely expressed in the central and peripheral nervous
      systems and is proliferative for a range of cells types in vitro. NPY plays a key
      role in regulating adult hippocampal neurogenesis in vivo under both basal and
      pathological conditions, although the underlying mechanisms are largely unknown.
      We have investigated the role of nitric oxide (NO) on the neurogenic effects of
      NPY. Using postnatal rat hippocampal cultures, we show that the proliferative
      effect of NPY on nestin(+) precursor cells is NO-dependent. As well as the
      involvement of neuronal nitric-oxide synthase, the proliferative effect is
      mediated via an NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein
      kinase (PKG) and extracellular signal-regulated kinase (ERK) 1/2 signaling
      pathway. We show that NPY-mediated intracellular NO signaling results in an
      increase in neuroproliferation. By contrast, extracellular NO had an opposite,
      inhibitory effect on proliferation. The importance of the NO-cGMP-PKG signaling
      pathway in ERK1/2 activation was confirmed using Western blotting. This work
      unites two significant modulators of hippocampal neurogenesis within a common
      signaling framework and provides a mechanism for the independent extra- and
      intracellular regulation of postnatal neural precursors by NO.

PMID- 22474321
TI  - Casein kinase 2-mediated synaptic GluN2A up-regulation increases N-methyl-D
      aspartate receptor activity and excitability of hypothalamic neurons in
      hypertension.
AB  - Increased glutamatergic input, particularly N-methyl-D-aspartate receptor (NMDAR)
      activity, in the paraventricular nucleus (PVN) of the hypothalamus is closely
      associated with high sympathetic outflow in essential hypertension. The molecular
      mechanisms underlying augmented NMDAR activity in hypertension are unclear. GluN2
      subunit composition at the synaptic site critically determines NMDAR functional
      properties. Here, we found that evoked NMDAR-excitatory postsynaptic currents
      (EPSCs) of retrogradely labeled spinally projecting PVN neurons displayed a
      larger amplitude and shorter decay time in spontaneously hypertensive rats (SHRs)
      than in Wistar-Kyoto (WKY) rats. Blocking GluN2B caused a smaller decrease in
      NMDAR-EPSCs of PVN neurons in SHRs than in WKY rats. In contrast, GluN2A blockade
      resulted in a larger reduction in evoked NMDAR-EPSCs and puff NMDA-elicited
      currents of PVN neurons in SHRs than in WKY rats. Blocking presynaptic GluN2A,
      but not GluN2B, significantly reduced the frequency of miniature EPSCs and the
      firing activity of PVN neurons in SHRs. The mRNA and total protein levels of
      GluN2A and GluN2B in the PVN were greater in SHRs than in WKY rats. Furthermore,
      the GluN2B Ser(1480) phosphorylation level and the synaptosomal GluN2A protein
      level in the PVN were significantly higher in SHRs than in WKY rats. Inhibition
      of protein kinase CK2 normalized the GluN2B Ser(1480) phosphorylation level and
      the contribution of GluN2A to NMDAR-EPSCs and miniature EPSCs of PVN neurons in
      SHRs. Collectively, our findings suggest that CK2-mediated GluN2B phosphorylation
      contributes to increased synaptic GluN2A, which potentiates pre- and postsynaptic
      NMDAR activity and the excitability of PVN presympathetic neurons in
      hypertension.

PMID- 22474322
TI  - Desensitization mechanism in prokaryotic ligand-gated ion channel.
AB  - Crystal structures of Gloeobacter violaceus ligand-gated ion channel (GLIC), a
      proton-gated prokaryotic homologue of pentameric ligand-gated ion channel (LGIC)
      from G. violaceus, have provided high-resolution models of the channel
      architecture and its role in selective ion conduction and drug binding. However,
      it is still unclear which functional states of the LGIC gating scheme these
      crystal structures represent. Much of this uncertainty arises from a lack of
      thorough understanding of the functional properties of these prokaryotic
      channels. To elucidate the molecular events that constitute gating, we have
      carried out an extensive characterization of GLIC function and dynamics in
      reconstituted proteoliposomes by patch clamp measurements and EPR spectroscopy.
      We find that GLIC channels show rapid activation upon jumps to acidic pH followed
      by a time-dependent loss of conductance because of desensitization. GLIC
      desensitization is strongly coupled to activation and is modulated by voltage,
      permeant ions, pore-blocking drugs, and membrane cholesterol. Many of these
      properties are parallel to functions observed in members of eukaryotic LGIC.
      Conformational changes in loop C, measured by site-directed spin labeling and EPR
      spectroscopy, reveal immobilization during desensitization analogous to changes
      in LGIC and acetylcholine binding protein. Together, our studies suggest
      conservation of mechanistic aspects of desensitization among LGICs of prokaryotic
      and eukaryotic origin.

PMID- 22474323
TI  - Prostaglandin EP1 receptor down-regulates expression of cyclooxygenase-2 by
      facilitating its proteasomal degradation.
AB  - The enzyme cyclooxygenase-2 (COX-2) is rapidly and transiently up-regulated by a
      large variety of signals and implicated in pathologies such as inflammation and
      tumorigenesis. Although many signals cause COX-2 up-regulation, much less is
      known about mechanisms that actively down-regulate its expression. Here we show
      that the G protein-coupled receptor prostaglandin E(1) (EP(1)) reduces the
      expression of COX-2 in a concentration-dependent manner through a mechanism that
      does not require receptor activation. The reduction in COX-2 protein is not due
      to decreased protein synthesis and occurs because of enhancement of substrate
      independent COX-2 proteolysis. Although EP(1) does not interfere with the entry
      of COX-2 into the endoplasmic reticulum-associated degradation cascade, it
      facilitates COX-2 ubiquitination through complex formation. Blockade of
      proteasomal activity results in degradation of the receptor and concomitant
      recovery in the expression of COX-2, suggesting that EP(1) may scaffold an
      unknown E3 ligase that ubiquitinates COX-2. These findings propose a new role for
      the EP(1) receptor in resolving inflammation through down-regulation of COX-2.

PMID- 22474324
TI  - Binding modes of zaragozic acid A to human squalene synthase and staphylococcal
      dehydrosqualene synthase.
AB  - Zaragozic acids (ZAs) belong to a family of fungal metabolites with nanomolar
      inhibitory activity toward squalene synthase (SQS). The enzyme catalyzes the
      committed step of sterol synthesis and has attracted attention as a potential
      target for antilipogenic and antiinfective therapies. Here, we have determined
      the structure of ZA-A complexed with human SQS. ZA-A binding induces a local
      conformational change in the substrate binding site, and its C-6 acyl group also
      extends over to the cofactor binding cavity. In addition, ZA-A effectively
      inhibits a homologous bacterial enzyme, dehydrosqualene synthase (CrtM), which
      synthesizes the precursor of staphyloxanthin in Staphylococcus aureus to cope
      with oxidative stress. Size reduction at Tyr(248) in CrtM further increases the
      ZA-A binding affinity, and it reveals a similar overall inhibitor binding mode to
      that of human SQS/ZA-A except for the C-6 acyl group. These structures pave the
      way for further improving selectivity and development of a new generation of
      anticholesterolemic and antimicrobial inhibitors.

PMID- 22474325
TI  - Profound hypoglycemia in starved, ghrelin-deficient mice is caused by decreased
      gluconeogenesis and reversed by lactate or fatty acids.
AB  - When mice are subjected to 7-day calorie restriction (40% of normal food intake),
      body fat disappears, but blood glucose is maintained as long as the animals
      produce ghrelin, an octanoylated peptide that stimulates growth hormone
      secretion. Mice can be rendered ghrelin-deficient by knock-out of the gene
      encoding either ghrelin O-acyltransferase, which attaches the required octanoate,
      or ghrelin itself. Calorie-restricted, fat-depleted ghrelin O-acyltransferase or
      ghrelin knock-out mice fail to show the normal increase in growth hormone and
      become profoundly hypoglycemic when fasted for 18-23 h. Glucose production in
      Goat(-/-) mice was reduced by 60% when compared with similarly treated WT mice.
      Plasma lactate and pyruvate were also low. Injection of lactate, pyruvate,
      alanine, or a fatty acid restored blood glucose in Goat(-/-) mice. Thus, when
      body fat is reduced by calorie restriction, ghrelin stimulates growth hormone
      secretion, which allows maintenance of glucose production, even when food intake
      is eliminated. In humans with anorexia nervosa or kwashiorkor, ghrelin and growth
      hormone are known to be elevated, just as they are in fat-depleted mice. We
      suggest that these two hormones prolong survival in starved humans as they do in
      mice.

PMID- 22474326
TI  - Calcium-induced conformational changes in C-terminal tail of polycystin-2 are
      necessary for channel gating.
AB  - Polycystin-2 (PC2) is a Ca(2+)-permeable transient receptor potential channel
      activated and regulated by changes in cytoplasmic Ca(2+). PC2 mutations are
      responsible for ~15% of autosomal dominant polycystic kidney disease. Although
      the C-terminal cytoplasmic tail of PC2 has been shown to contain a Ca(2+)-binding
      EF-hand domain, the molecular basis of PC2 channel gating by Ca(2+) remains
      unknown. We propose that the PC2 EF-hand is a Ca(2+) sensor required for channel
      gating. Consistent with this, Ca(2+) binding causes a dramatic decrease in the
      radius of gyration (R(g)) of the PC2 EF-hand by small angle x-ray scattering and
      significant conformational changes by NMR. Furthermore, increasing Ca(2+)
      concentrations cause the C-terminal cytoplasmic tail to transition from a mixture
      of extended oligomers to a single compact dimer by analytical
      ultracentrifugation, coupled with a >30 A decrease in maximum interatomic
      distance (D(max)) by small angle x-ray scattering. Mutant PC2 channels unable to
      bind Ca(2+) via the EF-hand are inactive in single-channel planar lipid bilayers
      and inhibit Ca(2+) release from ER stores upon overexpression in cells,
      suggesting dominant negative properties. Our results support a model where PC2
      channels are gated by discrete conformational changes in the C-terminal
      cytoplasmic tail in response to changes in cytoplasmic Ca(2+) levels. These
      properties of PC2 are lost in autosomal dominant polycystic kidney disease,
      emphasizing the importance of PC2 to kidney cell function. We speculate that PC2
      and the Ca(2+)-dependent transient receptor potential channels in general are
      regulated by similar conformational changes in their cytoplasmic domains that are
      propagated to the channel pore.

PMID- 22474327
TI  - Interaction of Notch signaling modulator Numb with alpha-Adaptin regulates
      endocytosis of Notch pathway components and cell fate determination of neural
      stem cells.
AB  - The ability to balance self-renewal and differentiation is a hallmark of stem
      cells. In Drosophila neural stem cells (NSCs), Numb/Notch (N) signaling plays a
      key role in this process. However, the molecular and cellular mechanisms
      underlying Numb function in a stem cell setting remain poorly defined. Here we
      show that alpha-Adaptin (alpha-Ada), a subunit of the endocytic AP-2 complex,
      interacts with Numb through a new mode of interaction to regulate NSC
      homeostasis. In alpha-ada mutants, N pathway component Sanpodo and the N receptor
      itself exhibited altered trafficking, and N signaling was up-regulated in the
      intermediate progenitors of type II NSC lineages, leading to their transformation
      into ectopic NSCs. Surprisingly, although the Ear domain of alpha-Ada interacts
      with the C terminus of Numb and is important for alpha-Ada function in the
      sensory organ precursor lineage, it was dispensable in the NSCs. Instead, alpha
      Ada could regulate Sanpodo, N trafficking, and NSC homeostasis by interacting
      with Numb through new domains in both proteins previously not known to mediate
      their interaction. This interaction could be bypassed when alpha-Ada was directly
      fused to the phospho-tyrosine binding domain of Numb. Our results identify a
      critical role for the AP-2-mediated endocytosis in regulating NSC behavior and
      reveal a new mechanism by which Numb regulates NSC behavior through N. These
      findings are likely to have important implications for cancer biology.

PMID- 22474328
TI  - O-linked N,N'-diacetyllactosamine (LacdiNAc)-modified glycans in extracellular
      matrix glycoproteins are specifically phosphorylated at subterminal N
      acetylglucosamine.
AB  - The terminal modification of glycans by beta4 addition of N-acetylgalactosamine
      to N-acetylglucosamine with formation of the N,N-diacetyllactosediamine
      (LacdiNAc) moiety has been well documented for a number of N-linked glycoproteins
      and peptides, like neurohormones. Much less is known about O-glycoproteins in
      this regard because only human zona pellucida glycoprotein 3 (ZP3) and bovine
      proopiomelanocortin were reported to be LacdiNAc-modified. In searching for
      mammalian proteins modified with O-linked LacdiNAc we identified six positive
      species among nine endogenous and recombinant O-glycoproteins, which were
      extracellular matrix, or matrix-related proteins. These are ZP3 and the five
      novel LacdiNAc-positive species ECM1, AMACO, nidogen-1, alpha-dystroglycan, and
      neurofascin. The mass spectrometric analyses revealed a core 2-based
      tetrasaccharide as the common structural basis of O-linked LacdiNAc that could be
      further modified, similar to the type 2 LacNAc termini, with fucose, sialic acid,
      or sulfate. Here, we provide structural evidence for a novel type of mucin-type O
      glycans that is strictly specific for LacdiNAc termini: sugar phosphorylation
      with formation of GalNAcbeta1-4(phospho-)GlcNAc. The structural details of the
      phosphatase-labile compound were elucidated by MS(2) analysis of tetralysine
      complexes and by MS(n) measurements of the permethylated glycan alditols. Phospho
      LacdiNAc was detected in human HEK-293 as well as in mouse myoblast cells and in
      bovine brain tissue.

PMID- 22474329
TI  - A comparative study of stress-mediated immunological functions with the
      adjuvanticity of alum.
AB  - The efficacy of a vaccine is generally dependent on an adjuvant, which enhances
      the immune functions and alum has been widely used in human immunization. Alum
      activates the intracellular stress sensors inflammasomes, but whether these are
      responsible for the adjuvanticity is controversial. The objectives of this
      investigation were to examine the hypothesis that alum-mediated adjuvanticity is
      a function of stress and conversely that stress agents will elicit adjuvanticity.
      The investigation was carried out in BALB/c mice by SC immunization with
      ovalbumin (OVA) mixed with alum. This elicited inflammasomes, with significant
      activation of caspase 1, production of IL-1beta, and adjuvanticity, demonstrated
      by enhancing OVA-specific serum IgG antibodies, CD4(+) T cells, and
      proliferation. The novel finding that alum induced HSP70 suggests that stress is
      involved in the mechanism of adjuvanticity. This was confirmed by inhibition
      studies with PES (phenylethynesulfonamide), which disrupts inducible HSP70
      function, and inhibited both inflammasomes and the adjuvant function. Parallel
      studies were pursued with an oxidative agent (sodium arsenite), K-releasing agent
      (Gramicidin) and a metal ionophore (dithiocarbamate). All 3 stress agents induced
      HSP70, inflammasomes, and the adjuvant functions. Furthermore, up-regulation of
      membrane associated IL-15 on DC and CD40L on T cells in the animals treated with
      alum or the stress agents mediate the interactions between splenic CD11c DC and
      CD4(+) or CD8(+) T cells. The results suggest that the three stress agents elicit
      HSP70, a hallmark of stress, as well as inflammasomes and adjuvanticity,
      commensurate with those of alum, which may provide an alternative strategy in
      developing novel adjuvants.

PMID- 22474330
TI  - Stable IL-2 decision making by endogenous c-Fos amounts in peripheral memory T
      helper cells.
AB  - The cytokine IL-2 performs opposite functions supporting efficient immune
      responses and playing a key role in peripheral tolerance. Therefore, precise fine
      tuning of IL-2 expression is crucial for adjusting the immune response. Combining
      transcription factor analysis at the single cell and the single nucleus level
      using flow cytometry with statistical analysis, we showed that physiological
      differences in the expression levels of c-Fos and NFATc2, but not of c-Jun and NF
      kappaBp65, are limiting for the decision whether IL-2 is expressed in a strongly
      activated human memory T-helper (Th) cell. Variation in the expression of c-Fos
      leads to substantial diversity of IL-2 expression in ~40% of the memory Th cells.
      The remaining cells exhibit an equally high c-Fos expression level, thereby
      ensuring robustness in IL-2 response within the population. These findings reveal
      how memory Th cells benefit from regulated variation in transcription factor
      expression to achieve a certain stability and variability of cytokine expression
      in a controlled manner.

PMID- 22474331
TI  - Vav1 oncogenic mutation inhibits T cell receptor-induced calcium mobilization
      through inhibition of phospholipase Cgamma1 activation.
AB  - Robust elevation of the cytosolic calcium concentration is a crucial early step
      for T cell activation triggered by the T cell antigen receptor. Vav1 is a proto
      oncogene expressed in hematopoietic cells that is indispensable for transducing
      the calcium-mobilizing signal. Following T cell receptor stimulation, Vav1
      facilitates formation of signaling microclusters through multiple interactions
      with other proteins participating in the signaling cascade. Truncation of the N
      terminus of Vav1 produces its oncogenic version, which is unable to support
      normal calcium flux following T cell activation. We show here that truncation of
      the N-terminal region of Vav1 alters the fine structure of protein complexes in
      the signaling clusters, affecting the interaction of Vav1 with phospholipase
      Cgamma1 (PLCgamma1). This alteration is accompanied by a decrease in PLCgamma1
      phosphorylation and inhibition of inositol 1,4,5-trisphosphate production. We
      suggest that the structural integrity of the N-terminal region of Vav1 is
      important for the proper formation of the Vav1-associated signaling complexes.
      The oncogenic truncation of this region elicits conformational changes that
      interfere with the Vav1-mediated activation of PLCgamma1 and that inhibit calcium
      mobilization.

PMID- 22474332
TI  - SdhE is a conserved protein required for flavinylation of succinate dehydrogenase
      in bacteria.
AB  - Conserved uncharacterized genes account for ~30% of genes in both eukaryotic and
      bacterial genomes and are predicted to encode what are often termed "conserved
      hypothetical proteins." Many of these proteins have a wide phylogenetic
      distribution and might play important roles in conserved cellular pathways. Using
      the bacterium Serratia as a model system, we have investigated two conserved
      uncharacterized proteins, YgfY (a DUF339 protein, renamed SdhE; succinate
      dehydrogenase protein E) and YgfX (a DUF1434 protein). SdhE was required for
      growth on succinate as a sole carbon source and for the function, but not
      stability, of succinate dehydrogenase, an important component of the electron
      transport chain and the tricarboxylic acid cycle. SdhE interacted with the
      flavoprotein SdhA, directly bound the flavin adenine dinucleotide co-factor, and
      was required for the flavinylation of SdhA. This is the first demonstration of a
      protein required for FAD incorporation in bacteria. Furthermore, the loss of SdhE
      was highly pleiotropic, suggesting that SdhE might flavinylate other
      flavoproteins. Our findings are of wide importance to central metabolism because
      SdhE homologues are present in alpha-, beta-, and gamma-proteobacteria and
      multiple eukaryotes, including humans and yeast.

PMID- 22474333
TI  - Functional linkage of adenine nucleotide binding sites in mammalian muscle 6
      phosphofructokinase.
AB  - 6-Phosphofructokinases (Pfk) are homo- and heterooligomeric, allosteric enzymes
      that catalyze one of the rate-limiting steps of the glycolysis: the
      phosphorylation of fructose 6-phosphate at position 1. Pfk activity is modulated
      by a number of regulators including adenine nucleotides. Recent crystal
      structures from eukaryotic Pfk revealed several adenine nucleotide binding sites.
      Herein, we determined the functional relevance of two adenine nucleotide binding
      sites through site-directed mutagenesis and enzyme kinetic studies. Subsequent
      characterization of Pfk mutants allowed the identification of the activating
      (AMP, ADP) and inhibitory (ATP, ADP) allosteric binding sites. Mutation of one
      binding site reciprocally influenced the allosteric regulation through
      nucleotides interacting with the other binding site. Such reciprocal linkage
      between the activating and inhibitory binding sites is in agreement with current
      models of allosteric enzyme regulation. Because the allosteric nucleotide binding
      sites in eukaryotic Pfk did not evolve from prokaryotic ancestors, reciprocal
      linkage of functionally opposed allosteric binding sites must have developed
      independently in prokaryotic and eukaryotic Pfk (convergent evolution).

PMID- 22474334
TI  - Multiple cholesterol recognition/interaction amino acid consensus (CRAC) motifs
      in cytosolic C tail of Slo1 subunit determine cholesterol sensitivity of Ca2+-
      and voltage-gated K+ (BK) channels.
AB  - Large conductance, Ca(2+)- and voltage-gated K(+) (BK) channel proteins are
      ubiquitously expressed in cell membranes and control a wide variety of biological
      processes. Membrane cholesterol regulates the activity of membrane-associated
      proteins, including BK channels. Cholesterol modulation of BK channels alters
      action potential firing, colonic ion transport, smooth muscle contractility,
      endothelial function, and the channel alcohol response. The structural bases
      underlying cholesterol-BK channel interaction are unknown. Such interaction is
      determined by strict chemical requirements for the sterol molecule, suggesting
      cholesterol recognition by a protein surface. Here, we demonstrate that
      cholesterol action on BK channel-forming Cbv1 proteins is mediated by their
      cytosolic C tail domain, where we identified seven cholesterol
      recognition/interaction amino acid consensus motifs (CRAC4 to 10), a distinct
      feature of BK proteins. Cholesterol sensitivity is provided by the membrane
      adjacent CRAC4, where Val-444, Tyr-450, and Lys-453 are required for cholesterol
      sensing, with hydrogen bonding and hydrophobic interactions participating in
      cholesterol location and recognition. However, cumulative truncations or Tyr-to
      Phe substitutions in CRAC5 to 10 progressively blunt cholesterol sensitivity,
      documenting involvement of multiple CRACs in cholesterol-BK channel interaction.
      In conclusion, our study provides for the first time the structural bases of BK
      channel cholesterol sensitivity; the presence of membrane-adjacent CRAC4 and the
      long cytosolic C tail domain with several other CRAC motifs, which are not found
      in other members of the TM6 superfamily of ion channels, very likely explains the
      unique cholesterol sensitivity of BK channels.

PMID- 22474335
TI  - Stabilization of p53 in influenza A virus-infected cells is associated with
      compromised MDM2-mediated ubiquitination of p53.
AB  - Influenza A virus (IAV) induces apoptosis of infected cells. In response to IAV
      infection, p53, a tumor suppressor involved in regulating apoptosis and host
      antiviral defense, accumulates and becomes activated. This study was undertaken
      to examine the mechanism of p53 accumulation in IAV-infected cells. Here we show
      that p53 accumulation in IAV-infected cells results from protein stabilization,
      which was associated with compromised Mdm2-mediated ubiquitination of p53. In IAV
      infected cells, p53 was stabilized and its half-life was remarkably extended. The
      ladders of polyubiquitinated p53 were not detectable in the presence of the
      proteasome inhibitor MG132 and were less sensitive to proteasome-mediated
      degradation. IAV infection did not affect the abundance of Mdm2, a major
      ubiquitin E3 ligase responsible for regulating p53 ubiquitination and
      degradation, but weakened the interaction between p53 and Mdm2. Viral
      nucleoprotein (NP) was able to increase the transcriptional activity and
      stability of p53. Furthermore, NP was found to associate with p53 and to impair
      the p53-Mdm2 interaction and Mdm2-mediated p53 ubiquitination, demonstrating its
      role in inhibiting Mdm2-mediated p53 ubiquitination and degradation.

PMID- 22474336
TI  - Interaction of voltage-gated sodium channel Nav1.6 (SCN8A) with microtubule
      associated protein Map1b.
AB  - The mechanism by which voltage-gated sodium channels are trafficked to the
      surface of neurons is not well understood. Our previous work implicated the
      cytoplasmic N terminus of the sodium channel Na(v)1.6 in this process. We report
      that the N terminus plus the first transmembrane segment (residues 1-153) is
      sufficient to direct a reporter to the cell surface. To identify proteins that
      interact with the 117-residue N-terminal domain, we carried out a yeast two
      hybrid screen of a mouse brain cDNA library. Three clones containing overlapping
      portions of the light chain of microtubule-associated protein Map1b (Mtap1b) were
      recovered from the screen. Interaction between endogenous Na(v)1.6 channels and
      Map1b in mouse brain was confirmed by co-immunoprecipitation. Map1b did not
      interact with the N terminus of the related channel Na(v)1.1. Alanine-scanning
      mutagenesis of the Na(v)1.6 N terminus demonstrated that residues 77-80 (VAVP)
      contribute to interaction with Map1b. Co-expression of Na(v)1.6 with Map1b in
      neuronal cell line ND7/23 resulted in a 50% increase in current density,
      demonstrating a functional role for this interaction. Mutation of the Map1b
      binding site of Na(v)1.6 prevented generation of sodium current in transfected
      cells. The data indicate that Map1b facilitates trafficking of Na(v)1.6 to the
      neuronal cell surface.

PMID- 22474337
TI  - Biotinylation of lysine method identifies acetylated histone H3 lysine 79 in
      Saccharomyces cerevisiae as a substrate for Sir2.
AB  - Although the biological roles of many members of the sirtuin family of lysine
      deacetylases have been well characterized, a broader understanding of their role
      in biology is limited by the challenges in identifying new substrates. We present
      here an in vitro method that combines biotinylation and mass spectrometry (MS) to
      identify substrates deacetylated by sirtuins. The method permits labeling of
      deacetylated residues with amine-reactive biotin on the epsilon-nitrogen of
      lysine. The biotin can be utilized to purify the substrate and identify the
      deacetylated lysine by MS. The biotinyl-lysine method was used to compare
      deacetylation of chemically acetylated histones by the yeast sirtuins, Sir2 and
      Hst2. Intriguingly, Sir2 preferentially deacetylates histone H3 lysine 79 as
      compared to Hst2. Although acetylation of K79 was not previously reported in
      Saccharomyces cerevisiae, we demonstrate that a minor population of this residue
      is indeed acetylated in vivo and show that Sir2, and not Hst2, regulates the
      acetylation state of H3 lysine 79. The in vitro biotinyl-lysine method combined
      with chemical acetylation made it possible to identify this previously unknown,
      low-abundance histone acetyl modification in vivo. This method has further
      potential to identify novel sirtuin deacetylation substrates in whole cell
      extracts, enabling large-scale screens for new deacetylase substrates.

PMID- 22474338
TI  - Step-by-step self-assembled hybrids that feature control over energy and charge
      transfer.
AB  - In the current work, we have documented the use of two complementary
      supramolecular motifs, namely multipoint hydrogen bonding and metal complexation,
      as a means to control the step-by-step assembly of a panchromatically absorbing
      and highly versatile solar energy conversion system. On one hand, two different
      perylenediimides (1a/1b) have been integrated together with a metalloporphyrin
      (2) by means of the Hamilton receptor/cyanuric acid hydrogen bonding motif into
      energy transduction systems 1a*2 or 1b*2. Steady-state and time-resolved
      measurements corroborated that upon selective photoexcitation of the
      perylenediimides (1a/1b), an energy transfer evolved from the singlet excited
      state of the perylenediimides (1a/1b) to that of the metalloporphyrin (2). On the
      other hand, fullerene (3) and metalloporphyrin (2) form the electron donor
      acceptor system 2*3 via axial complexation. Photophysical measurements confirm
      that an electron transfer prevails from the singlet excited state of 2 to the
      electron-accepting 3. The correspondingly formed radical ion pair state decays
      with a lifetime of 1.0 +/- 0.1 ns. As a complement to the aforementioned, the
      energy transduction features of 1a*2 were combined with the electron donor
      acceptor characteristics of 2*3 to afford 1a*2*3. To this end, time-resolved
      measurements reveal that the initially occurring energy-transfer interaction (53
      +/- 3 ps) between 1a/1b and 2 is followed by an electron transfer (12 +/- 1 ps)
      from 2 to 3. From multiwavelength analyses, the lifetime of the radical ion pair
      state in 1a*2*3-as a product of a cascade of light-induced energy and electron
      transfer-was derived as 3.8 +/- 0.2 ns.

PMID- 22474339
TI  - Shift-driven modulations of spin-echo signals.
AB  - Since the pioneering works of Carr-Purcell and Meiboom-Gill [Carr HY, Purcell EM
      (1954) Phys Rev 94:630; Meiboom S, Gill D (1985) Rev Sci Instrum 29:688], trains
      of pi-pulses have featured amongst the main tools of quantum control. Echo trains
      find widespread use in nuclear magnetic resonance spectroscopy (NMR) and imaging
      (MRI), thanks to their ability to free the evolution of a spin-1/2 from several
      sources of decoherence. Spin echoes have also been researched in dynamic
      decoupling scenarios, for prolonging the lifetimes of quantum states or
      coherences. Inspired by this search we introduce a family of spin-echo sequences,
      which can still detect site-specific interactions like the chemical shift. This
      is achieved thanks to the presence of weak environmental fluctuations of common
      occurrence in high-field NMR--such as homonuclear spin-spin couplings or
      chemical/biochemical exchanges. Both intuitive and rigorous derivations of the
      resulting "selective dynamical recoupling" sequences are provided. Applications
      of these novel experiments are given for a variety of NMR scenarios including
      determinations of shift effects under inhomogeneities overwhelming individual
      chemical identities, and model-free characterizations of chemically exchanging
      partners.

PMID- 22474340
TI  - Coupling of the fusion and budding of giant phospholipid vesicles containing
      macromolecules.
AB  - Mechanisms that enabled primitive cell membranes to self-reproduce have been
      discussed based on the physicochemical properties of fatty acids; however, there
      must be a transition to modern cell membranes composed of phospholipids [Budin I,
      Szostak JW (2011) Proc Natl Acad Sci USA 108:5249-5254]. Thus, a growth-division
      mechanism of membranes that does not depend on the chemical nature of amphiphilic
      molecules must have existed. Here, we show that giant unilamellar vesicles
      composed of phospholipids can undergo the coupled process of fusion and budding
      transformation, which mimics cell growth and division. After gaining excess
      membrane by electrofusion, giant vesicles spontaneously transform into the budded
      shape only when they contain macromolecules (polymers) inside their aqueous core.
      This process is a result of the vesicle maximizing the translational entropy of
      the encapsulated polymers (depletion volume effect). Because the cell is a lipid
      membrane bag containing highly concentrated biopolymers, this coupling process
      that is induced by physical and nonspecific interactions may have a general
      importance in the self-reproduction of the early cellular compartments.

PMID- 22474341
TI  - ATP drives direct photosynthetic production of 1-butanol in cyanobacteria.
AB  - While conservation of ATP is often a desirable trait for microbial production of
      chemicals, we demonstrate that additional consumption of ATP may be beneficial to
      drive product formation in a nonnatural pathway. Although production of 1-butanol
      by the fermentative coenzyme A (CoA)-dependent pathway using the reversal of beta
      oxidation exists in nature and has been demonstrated in various organisms, the
      first step of the pathway, condensation of two molecules of acetyl-CoA to
      acetoacetyl-CoA, is thermodynamically unfavorable. Here, we show that
      artificially engineered ATP consumption through a pathway modification can drive
      this reaction forward and enables for the first time the direct photosynthetic
      production of 1-butanol from cyanobacteria Synechococcus elongatus PCC 7942. We
      further demonstrated that substitution of bifunctional aldehyde/alcohol
      dehydrogenase (AdhE2) with separate butyraldehyde dehydrogenase (Bldh) and NADPH
      dependent alcohol dehydrogenase (YqhD) increased 1-butanol production by 4-fold.
      These results demonstrated the importance of ATP and cofactor driving forces as a
      design principle to alter metabolic flux.

PMID- 22474342
TI  - Similar temporal and spatial recruitment of native 19S and 20S proteasome
      subunits to transcriptionally active chromatin.
AB  - It has recently become clear that components of the proteasome are recruited to
      sites of gene transcription. Prevailing evidence suggests that the
      transcriptionally relevant form of the proteasome is a subcomplex of 19S base
      proteins, which functions as an ATP-dependent chaperone that influences
      transcriptional processes. Despite this notion, compelling evidence for a
      transcription-dedicated 19S base complex is lacking, and 20S proteasome subunits
      have been shown to associate with chromatin in some contexts. To gain insight
      into the form of the proteasome that is recruited to chromatin, we assembled a
      panel of highly specific antibodies that recognize native yeast proteasome
      subunits in chromatin immunoprecipitation assays. Using these reagents, we show
      that components from the three major subassemblies of the proteasome--19S lid,
      19S base, and 20S core--associate with the activated GAL10 gene in yeast in a
      virtually indistinguishable manner. We find that proteasome subunits Rpt1, Rpt4,
      Rpn8, Rpn12, Pre6, and Pre10 are recruited to GAL10 rapidly upon galactose
      induction. These subunits associate with the entire transcribed portion of GAL10,
      display near-identical patterns of distribution, and dissociate from chromatin
      rapidly once transcription is shut down. We also find that proteasome subunits
      are enriched at telomeres and at genes transcribed by RNA polymerase III. Our
      data suggest that the transcriptionally relevant form of the proteasome is the
      canonical 26S complex.

PMID- 22474343
TI  - Biosynthetic pathway toward carbohydrate-like moieties of alnumycins contains
      unusual steps for C-C bond formation and cleavage.
AB  - Carbohydrate moieties are important components of natural products, which are
      often imperative for the solubility and biological activity of the compounds. The
      aromatic polyketide alnumycin A contains an extraordinary sugar-like 4'-hydroxy
      5'-hydroxymethyl-2',7'-dioxane moiety attached via a carbon-carbon bond to the
      aglycone. Here we have extensively investigated the biosynthesis of the dioxane
      unit through (13)C labeling studies, gene inactivation experiments and enzymatic
      synthesis. We show that AlnA and AlnB, members of the pseudouridine glycosidase
      and haloacid dehalogenase enzyme families, respectively, catalyze C-ribosylation
      conceivably through Michael-type addition of d-ribose-5-phosphate and
      dephosphorylation. The ribose moiety may be attached both in furanose (alnumycin
      C) and pyranose (alnumycin D) forms. The C(1')-C(2') bond of alnumycin C is
      subsequently cleaved and the ribose unit is rearranged into an unprecedented
      dioxolane (cis-bicyclo[3.3.0]-2',4',6'-trioxaoctan-3'beta-ol) structure present
      in alnumycin B. The reaction is catalyzed by Aln6, which belongs to a previously
      uncharacterized enzyme family. The conversion was accompanied with consumption of
      O(2) and formation of H(2)O(2), which allowed us to propose that the reaction may
      proceed via hydroxylation of C1' followed by retro-aldol cleavage and acetal
      formation. Interestingly, no cofactors could be detected and the reaction was
      also conducted in the presence of metal chelating agents. The last step is the
      conversion of alnumycin B into the final end-product alnumycin A catalyzed by
      Aln4, an NADPH-dependent aldo-keto reductase. This characterization of the
      dioxane biosynthetic pathway sets the basis for the utilization of C-C bound
      ribose, dioxolane and dioxane moieties in the generation of improved biologically
      active compounds.

PMID- 22474344
TI  - Microfluidic integration for automated targeted proteomic assays.
AB  - A dearth of protein isoform-based clinical diagnostics currently hinders advances
      in personalized medicine. A well-organized protein biomarker validation process
      that includes facile measurement of protein isoforms would accelerate development
      of effective protein-based diagnostics. Toward scalable protein isoform analysis,
      we introduce a microfluidic "single-channel, multistage" immunoblotting strategy.
      The multistep assay performs all immunoblotting steps: separation, immobilization
      of resolved proteins, antibody probing of immobilized proteins, and all interim
      wash steps. Programmable, low-dispersion electrophoretic transport obviates the
      need for pumps and valves. A three-dimensional bulk photoreactive hydrogel
      eliminates manual blotting. In addition to simplified operation and interfacing,
      directed electrophoretic transport through our 3D nanoporous reactive hydrogel
      yields superior performance over the state-of-the-art in enhanced capture
      efficiency (on par with membrane electroblotting) and sparing consumption of
      reagents (ca. 1 ng antibody), as supported by empirical and by scaling analyses.
      We apply our fully integrated microfluidic assay to protein measurements of
      endogenous prostate specific antigen isoforms in (i) minimally processed human
      prostate cancer cell lysate (1.1 pg limit of detection) and (ii) crude sera from
      metastatic prostate cancer patients. The single-instrument functionality
      establishes a scalable microfluidic framework for high-throughput targeted
      proteomics, as is relevant to personalized medicine through robust protein
      biomarker verification, systematic characterization of new antibody probes for
      functional proteomics, and, more broadly, to characterization of human
      biospecimen repositories.

PMID- 22474345
TI  - A hydrogen-bonding network plays a catalytic role in photosynthetic oxygen
      evolution.
AB  - In photosystem II, oxygen evolution occurs by the accumulation of photo-induced
      oxidizing equivalents at the oxygen-evolving complex (OEC). The sequentially
      oxidized states are called the S(0)-S(4) states, and the dark stable state is
      S(1). Hydrogen bonds to water form a network around the OEC; this network is
      predicted to involve multiple peptide carbonyl groups. In this work, we tested
      the idea that a network of hydrogen bonded water molecules plays a catalytic role
      in water oxidation. As probes, we used OEC peptide carbonyl frequencies, the
      substrate-based inhibitor, ammonia, and the sugar, trehalose. Reaction-induced FT
      IR spectroscopy was used to describe the protein dynamics associated with the
      S(1) to S(2) transition. A shift in an amide CO vibrational frequency (1664
      (S(1)) to 1653 (S(2)) cm(-1)) was observed, consistent with an increase in
      hydrogen bond strength when the OEC is oxidized. Treatment with ammonia/ammonium
      altered these CO vibrational frequencies. The ammonia-induced spectral changes
      are attributed to alterations in hydrogen bonding, when ammonia/ammonium is
      incorporated into the OEC hydrogen bond network. The ammonia-induced changes in
      CO frequency were reversed or blocked when trehalose was substituted for sucrose.
      This trehalose effect is attributed to a displacement of ammonia molecules from
      the hydrogen bond network. These results imply that ammonia, and by extension
      water, participate in a catalytically essential hydrogen bond network, which
      involves OEC peptide CO groups. Comparison to the ammonia transporter, AmtB,
      reveals structural similarities with the bound water network in the OEC.

PMID- 22474346
TI  - Structure of p73 DNA-binding domain tetramer modulates p73 transactivation.
AB  - The transcription factor p73 triggers developmental pathways and overlaps stress
      induced p53 transcriptional pathways. How p53-family response elements determine
      and regulate transcriptional specificity remains an unsolved problem. In this
      work, we have determined the first crystal structures of p73 DNA-binding domain
      tetramer bound to response elements with spacers of different length. The
      structure and function of the adaptable tetramer are determined by the distance
      between two half-sites. The structures with zero and one base-pair spacers show
      compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a
      two base-pair spacer results in DNA unwinding and a smaller tetramerization
      interface, whereas a four base-pair spacer hinders tetramerization. Functionally,
      p73 is more sensitive to spacer length than p53, with one base-pair spacer
      reducing 90% of transactivation activity and longer spacers reducing
      transactivation to basal levels. Our results establish the quaternary structure
      of the p73 DNA-binding domain required as a scaffold to promote transactivation.

PMID- 22474347
TI  - Induction of lignocellulose-degrading enzymes in Neurospora crassa by
      cellodextrins.
AB  - Neurospora crassa colonizes burnt grasslands in the wild and metabolizes both
      cellulose and hemicellulose from plant cell walls. When switched from a favored
      carbon source such as sucrose to cellulose, N. crassa dramatically upregulates
      expression and secretion of a wide variety of genes encoding lignocellulolytic
      enzymes. However, the means by which N. crassa and other filamentous fungi sense
      the presence of cellulose in the environment remains unclear. Here, we show that
      an N. crassa mutant carrying deletions of two genes encoding extracellular beta
      glucosidase enzymes and one intracellular beta-glucosidase lacks beta-glucosidase
      activity, but efficiently induces cellulase gene expression in the presence of
      cellobiose, cellotriose, or cellotetraose as a sole carbon source. These data
      indicate that cellobiose, or a modified version of cellobiose, functions as an
      inducer of lignocellulolytic gene expression in N. crassa. Furthermore, the
      inclusion of a deletion of the catabolite repressor gene, cre-1, in the triple
      beta-glucosidase mutant resulted in a strain that produces higher concentrations
      of secreted active cellulases on cellobiose. Thus, the ability to induce
      cellulase gene expression using a common and soluble carbon source simplifies
      enzyme production and characterization, which could be applied to other
      cellulolytic filamentous fungi.

PMID- 22474348
TI  - 9,400 years of cosmic radiation and solar activity from ice cores and tree rings.
AB  - Understanding the temporal variation of cosmic radiation and solar activity
      during the Holocene is essential for studies of the solar-terrestrial
      relationship. Cosmic-ray produced radionuclides, such as (10)Be and (14)C which
      are stored in polar ice cores and tree rings, offer the unique opportunity to
      reconstruct the history of cosmic radiation and solar activity over many
      millennia. Although records from different archives basically agree, they also
      show some deviations during certain periods. So far most reconstructions were
      based on only one single radionuclide record, which makes detection and
      correction of these deviations impossible. Here we combine different (10)Be ice
      core records from Greenland and Antarctica with the global (14)C tree ring record
      using principal component analysis. This approach is only possible due to a new
      high-resolution (10)Be record from Dronning Maud Land obtained within the
      European Project for Ice Coring in Antarctica in Antarctica. The new cosmic
      radiation record enables us to derive total solar irradiance, which is then used
      as a proxy of solar activity to identify the solar imprint in an Asian climate
      record. Though generally the agreement between solar forcing and Asian climate is
      good, there are also periods without any coherence, pointing to other forcings
      like volcanoes and greenhouse gases and their corresponding feedbacks. The newly
      derived records have the potential to improve our understanding of the solar
      dynamics and to quantify the solar influence on climate.

PMID- 22474349
TI  - Peierls distortion mediated reversible phase transition in GeTe under pressure.
AB  - With the advent of big synchrotron facilities around the world, pressure is now
      routinely placed to design a new material or manipulate the properties of
      materials. In GeTe, an important phase-change material that utilizes the property
      contrast between the crystalline and amorphous states for data storage, we
      observed a reversible phase transition of rhombohedral <-> rocksalt <->
      orthorhombic <-> monoclinic coupled with a semiconductor <-> metal
      interconversion under pressure on the basis of ab initio molecular dynamics
      simulations. This interesting reversible phase transition under pressure is
      believed to be mediated by Peierls distortion in GeTe. Our results suggest a
      unique way to understand the reversible phase transition and hence the resistance
      switching that is crucial to the applications of phase-change materials in
      nonvolatile memory. The present finding can also be expanded to other IV-VI
      semiconductors.

PMID- 22474350
TI  - Torque measurements reveal sequence-specific cooperative transitions in
      supercoiled DNA.
AB  - B-DNA becomes unstable under superhelical stress and is able to adopt a wide
      range of alternative conformations including strand-separated DNA and Z-DNA.
      Localized sequence-dependent structural transitions are important for the
      regulation of biological processes such as DNA replication and transcription. To
      directly probe the effect of sequence on structural transitions driven by torque,
      we have measured the torsional response of a panel of DNA sequences using single
      molecule assays that employ nanosphere rotational probes to achieve high torque
      resolution. The responses of Z-forming d(pGpC)(n) sequences match our predictions
      based on a theoretical treatment of cooperative transitions in helical polymers.
      "Bubble" templates containing 50-100 bp mismatch regions show cooperative
      structural transitions similar to B-DNA, although less torque is required to
      disrupt strand-strand interactions. Our mechanical measurements, including direct
      characterization of the torsional rigidity of strand-separated DNA, establish a
      framework for quantitative predictions of the complex torsional response of
      arbitrary sequences in their biological context.

PMID- 22474351
TI  - Target genes of Topoisomerase IIbeta regulate neuronal survival and are defined
      by their chromatin state.
AB  - Topoisomerases are essential for DNA replication in dividing cells, but their
      genomic targets and function in postmitotic cells remain poorly understood. Here
      we show that a switch in the expression from Topoisomerases IIalpha (Top2alpha)
      to IIbeta (Top2beta) occurs during neuronal differentiation in vitro and in vivo.
      Genome-scale location analysis in stem cell-derived postmitotic neurons reveals
      Top2beta binding to chromosomal sites that are methylated at lysine 4 of histone
      H3, a feature of regulatory regions. Indeed Top2beta-bound sites are
      preferentially promoters and become targets during the transition from neuronal
      progenitors to neurons, at a time when cells exit the cell cycle. Absence of
      Top2beta protein or its activity leads to changes in transcription and chromatin
      accessibility at many target genes. Top2beta deficiency does not impair stem cell
      properties and early steps of neuronal differentiation but causes premature death
      of postmitotic neurons. This neuronal degeneration is caused by up-regulation of
      Ngfr p75, a gene bound and repressed by Top2beta. These findings suggest a
      chromatin-based targeting of Top2beta to regulatory regions in the genome to
      govern the transcriptional program associated with neuronal differentiation and
      longevity.

PMID- 22474352
TI  - Viral-induced encephalitis initiates distinct and functional CD103+ CD11b+ brain
      dendritic cell populations within the olfactory bulb.
AB  - Dendritic cells (DC) are antigen-presenting cells found in both lymphoid and
      nonlymphoid organs, including the brain (bDC) of Cd11c/eyfp transgenic C57BL/6
      mice. Using an intranasal vesicular stomatitis virus infection, we demonstrated
      that EYFP(+) cells amass in areas associated with viral antigens, take on an
      activated morphology, and project their processes into infected neuronal tissue
      within the olfactory bulb. These bDC separated into three EYFP(+) CD45(+)
      CD11b(+) populations, all but one being able to functionally promote both T
      lymphocyte proliferation and T(H)1 cytokine production. One population was shown
      to emanate from the brain and a second population was peripherally derived. The
      third population was of indeterminate origin, being both radiosensitive and not
      replenished by donor bone marrow. Finally, each EYFP(+) population contained
      CD11b(+) CD103(+) subpopulations and could be distinguished in terms of CD115, Gr
      1, and Ly-6C expression, highlighting mucosal and monocyte-derived DC lineages.

PMID- 22474353
TI  - Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a
      mitochondrial complex I deficiency-specific cardiomyopathy.
AB  - Mitochondrial complex I (CI) deficiency is the most common mitochondrial enzyme
      defect in humans. Treatment of mitochondrial disorders is currently inadequate,
      emphasizing the need for experimental models. In humans, mutations in the NDUFS6
      gene, encoding a CI subunit, cause severe CI deficiency and neonatal death. In
      this study, we generated a CI-deficient mouse model by knockdown of the Ndufs6
      gene using a gene-trap embryonic stem cell line. Ndufs6(gt/gt) mice have
      essentially complete knockout of the Ndufs6 subunit in heart, resulting in marked
      CI deficiency. Small amounts of wild-type Ndufs6 mRNA are present in other
      tissues, apparently due to tissue-specific mRNA splicing, resulting in milder CI
      defects. Ndufs6(gt/gt) mice are born healthy, attain normal weight and maturity,
      and are fertile. However, after 4 mo in males and 8 mo in females, Ndufs6(gt/gt)
      mice are at increased risk of cardiac failure and death. Before overt heart
      failure, Ndufs6(gt/gt) hearts show decreased ATP synthesis, accumulation of
      hydroxyacylcarnitine, but not reactive oxygen species (ROS). Ndufs6(gt/gt) mice
      develop biventricular enlargement by 1 mo, most pronounced in males, with
      scattered fibrosis and abnormal mitochondrial but normal myofibrillar
      ultrastructure. Ndufs6(gt/gt) isolated working heart preparations show markedly
      reduced left ventricular systolic function, cardiac output, and functional work
      capacity. This reduced energetic and functional capacity is consistent with a
      known susceptibility of individuals with mitochondrial cardiomyopathy to
      metabolic crises precipitated by stresses. This model of CI deficiency will
      facilitate studies of pathogenesis, modifier genes, and testing of therapeutic
      approaches.

PMID- 22474354
TI  - Morphine activates neuroinflammation in a manner parallel to endotoxin.
AB  - Opioids create a neuroinflammatory response within the CNS, compromising opioid
      induced analgesia and contributing to various unwanted actions. How this occurs
      is unknown but has been assumed to be via classic opioid receptors. Herein, we
      provide direct evidence that morphine creates neuroinflammation via the
      activation of an innate immune receptor and not via classic opioid receptors. We
      demonstrate that morphine binds to an accessory protein of Toll-like receptor 4
      (TLR4), myeloid differentiation protein 2 (MD-2), thereby inducing TLR4
      oligomerization and triggering proinflammation. Small-molecule inhibitors, RNA
      interference, and genetic knockout validate the TLR4/MD-2 complex as a feasible
      target for beneficially modifying morphine actions. Disrupting TLR4/MD-2 protein
      protein association potentiated morphine analgesia in vivo and abolished morphine
      induced proinflammation in vitro, the latter demonstrating that morphine-induced
      proinflammation only depends on TLR4, despite the presence of opioid receptors.
      These results provide an exciting, nonconventional avenue to improving the
      clinical efficacy of opioids.

PMID- 22474355
TI  - Heterochromatin protein 1 homologue Swi6 acts in concert with Ers1 to regulate
      RNAi-directed heterochromatin assembly.
AB  - In fission yeast, the RNAi pathway is required for centromeric heterochromatin
      assembly. siRNAs derived from centromeric transcripts are incorporated into the
      RNA-induced transcriptional silencing (RITS) complex and direct it to nascent
      homologous transcripts. The RNA-induced transcriptional silencing-bound nascent
      transcripts further recruit the RNA-directed RNA polymerase complex (RDRC) to
      promote dsRNA synthesis and siRNA production. Heterochromatin coated with
      Swi6/Heterochromain Protein 1 is then formed following recruitment of chromatin
      modification machinery. Swi6 is also required for the upstream production of
      siRNA, although the mechanism for this has remained obscure. Here, we demonstrate
      that Swi6 recruits RDRC to heterochromatin through Ers1, an RNAi factor
      intermediate. An ers1(+) mutant allele (ers1-C62) was identified in a genetic
      screen for mutants that alleviate centromeric silencing, and this phenotype was
      suppressed by overexpression of either the Hrr1 RDRC subunit or Clr4 histone H3
      K9 methyltransferase. Ers1 physically interacts with Hrr1, and loss of Ers1
      impairs RDRC centromeric localization. Although Ers1 failed to bind Clr4, a
      direct interaction with Swi6 was detected, and centromeric localization of Swi6
      was enhanced by Clr4 overexpression in ers1-C62 cells. Consistent with this,
      deletion of swi6(+) reduced centromeric localization of Ers1 and RDRC. Moreover,
      tethering of Ers1 or Hrr1 to centromeric heterochromatin partially bypassed Swi6
      function. These findings demonstrate an alternative mechanism for RDRC
      recruitment and explain the essential role of Swi6/Heterochromain Protein 1 in
      RNAi-directed heterochromatin assembly.

PMID- 22474356
TI  - De novo design of synthetic prion domains.
AB  - Prions are important disease agents and epigenetic regulatory elements. Prion
      formation involves the structural conversion of proteins from a soluble form into
      an insoluble amyloid form. In many cases, this structural conversion is driven by
      a glutamine/asparagine (Q/N)-rich prion-forming domain. However, our
      understanding of the sequence requirements for prion formation and propagation by
      Q/N-rich domains has been insufficient for accurate prion propensity prediction
      or prion domain design. By focusing exclusively on amino acid composition, we
      have developed a prion aggregation prediction algorithm (PAPA), specifically
      designed to predict prion propensity of Q/N-rich proteins. Here, we show not only
      that this algorithm is far more effective than traditional amyloid prediction
      algorithms at predicting prion propensity of Q/N-rich proteins, but remarkably,
      also that PAPA is capable of rationally designing protein domains that function
      as prions in vivo.

PMID- 22474357
TI  - Correlative 3D superresolution fluorescence and electron microscopy reveal the
      relationship of mitochondrial nucleoids to membranes.
AB  - Microscopic images of specific proteins in their cellular context yield important
      insights into biological processes and cellular architecture. The advent of
      superresolution optical microscopy techniques provides the possibility to augment
      EM with nanometer-resolution fluorescence microscopy to access the precise
      location of proteins in the context of cellular ultrastructure. Unfortunately,
      efforts to combine superresolution fluorescence and EM have been stymied by the
      divergent and incompatible sample preparation protocols of the two methods. Here,
      we describe a protocol that preserves both the delicate photoactivatable
      fluorescent protein labels essential for superresolution microscopy and the fine
      ultrastructural context of EM. This preparation enables direct 3D imaging in 500-
      to 750-nm sections with interferometric photoactivatable localization microscopy
      followed by scanning EM images generated by focused ion beam ablation. We use
      this process to "colorize" detailed EM images of the mitochondrion with the
      position of labeled proteins. The approach presented here has provided a new
      level of definition of the in vivo nature of organization of mitochondrial
      nucleoids, and we expect this straightforward method to be applicable to many
      other biological questions that can be answered by direct imaging.

PMID- 22474358
TI  - Gene selective mRNA cleavage inhibits the development of Plasmodium falciparum.
AB  - Unique peptide-morpholino oligomer (PMO) conjugates have been designed to bind
      and promote the cleavage of specific mRNA as a tool to inhibit gene function and
      parasite growth. The new conjugates were validated using the P. falciparum gyrase
      mRNA as a target (PfGyrA). Assays in vitro demonstrated a selective degradation
      of the PfGyrA mRNA directed by the external guide sequences, which are morpholino
      oligomers in the conjugates. Fluorescence microscopy revealed that labeled
      conjugates are delivered into Plasmodium-infected erythrocytes during all
      intraerythrocytic stages of parasite development. Consistent with the expression
      of PfGyrA in all stages of parasite development, proliferation assays showed that
      these conjugates have potent antimalarial activity, blocking early development,
      maturation, and replication of the parasite. The conjugates were equally
      effective against drug sensitive and resistant P. falciparum strains. The
      potency, selectivity, and predicted safety of PMO conjugates make this approach
      attractive for the development of a unique class of target-specific antimalarials
      and for large-scale functional analysis of the malarial genome.

PMID- 22474359
TI  - Small molecule inhibitors of influenza A and B viruses that act by disrupting
      subunit interactions of the viral polymerase.
AB  - Influenza viruses are the cause of yearly epidemics and occasional pandemics that
      represent a significant challenge to public health. Current control strategies
      are imperfect and there is an unmet need for new antiviral therapies. Here, we
      report the identification of small molecule compounds able to effectively and
      specifically inhibit growth of influenza A and B viruses in cultured cells
      through targeting an assembly interface of the viral RNA-dependent RNA
      polymerase. Using an existing crystal structure of the primary protein-protein
      interface between the PB1 and PA subunits of the influenza A virus polymerase, we
      conducted an in silico screen to identify potential small molecule inhibitors.
      Selected compounds were then screened for their ability to inhibit the
      interaction between PB1 and PA in vitro using an ELISA-based assay and in cells,
      to inhibit nuclear import of a binary PB1-PA complex as well as transcription by
      the full viral ribonucleoprotein complex. Two compounds emerged as effective
      inhibitors with IC(50) values in the low micromolar range and negligible
      cytotoxicity. Of these, one compound also acted as a potent replication inhibitor
      of a variety of influenza A virus strains in Madin-Darby canine kidney (MDCK)
      cells, including H3N2 and H1N1 seasonal and 2009 pandemic strains. Importantly,
      this included an oseltamivir-resistant isolate. Furthermore, potent inhibition of
      influenza B viruses but not other RNA or DNA viruses was seen. Overall, these
      compounds provide a foundation for the development of a new generation of
      therapeutic agents exhibiting high specificity to influenza A and B viruses.

PMID- 22474360
TI  - Structural diversity in social contagion.
AB  - The concept of contagion has steadily expanded from its original grounding in
      epidemic disease to describe a vast array of processes that spread across
      networks, notably social phenomena such as fads, political opinions, the adoption
      of new technologies, and financial decisions. Traditional models of social
      contagion have been based on physical analogies with biological contagion, in
      which the probability that an individual is affected by the contagion grows
      monotonically with the size of his or her "contact neighborhood"--the number of
      affected individuals with whom he or she is in contact. Whereas this contact
      neighborhood hypothesis has formed the underpinning of essentially all current
      models, it has been challenging to evaluate it due to the difficulty in obtaining
      detailed data on individual network neighborhoods during the course of a large
      scale contagion process. Here we study this question by analyzing the growth of
      Facebook, a rare example of a social process with genuinely global adoption. We
      find that the probability of contagion is tightly controlled by the number of
      connected components in an individual's contact neighborhood, rather than by the
      actual size of the neighborhood. Surprisingly, once this "structural diversity"
      is controlled for, the size of the contact neighborhood is in fact generally a
      negative predictor of contagion. More broadly, our analysis shows how data at the
      size and resolution of the Facebook network make possible the identification of
      subtle structural signals that go undetected at smaller scales yet hold pivotal
      predictive roles for the outcomes of social processes.

PMID- 22474361
TI  - Natural disasters and population mobility in Bangladesh.
AB  - The consequences of environmental change for human migration have gained
      increasing attention in the context of climate change and recent large-scale
      natural disasters, but as yet relatively few large-scale and quantitative studies
      have addressed this issue. We investigate the consequences of climate-related
      natural disasters for long-term population mobility in rural Bangladesh, a region
      particularly vulnerable to environmental change, using longitudinal survey data
      from 1,700 households spanning a 15-y period. Multivariate event history models
      are used to estimate the effects of flooding and crop failures on local
      population mobility and long-distance migration while controlling for a large set
      of potential confounders at various scales. The results indicate that flooding
      has modest effects on mobility that are most visible at moderate intensities and
      for women and the poor. However, crop failures unrelated to flooding have strong
      effects on mobility in which households that are not directly affected but live
      in severely affected areas are the most likely to move. These results point
      toward an alternate paradigm of disaster-induced mobility that recognizes the
      significant barriers to migration for vulnerable households as well their
      substantial local adaptive capacity.

PMID- 22474362
TI  - RNA signatures allow rapid identification of pathogens and antibiotic
      susceptibilities.
AB  - With rising rates of drug-resistant infections, there is a need for diagnostic
      methods that rapidly can detect the presence of pathogens and reveal their
      susceptibility to antibiotics. Here we propose an approach to diagnosing the
      presence and drug-susceptibility of infectious diseases based on direct detection
      of RNA from clinical samples. We demonstrate that species-specific RNA signatures
      can be used to identify a broad spectrum of infectious agents, including
      bacteria, viruses, yeast, and parasites. Moreover, we show that the behavior of a
      small set of bacterial transcripts after a brief antibiotic pulse can rapidly
      differentiate drug-susceptible and -resistant organisms and that these
      measurements can be made directly from clinical materials. Thus, transcriptional
      signatures could form the basis of a uniform diagnostic platform applicable
      across a broad range of infectious agents.

PMID- 22474363
TI  - Evolution of the global virtual water trade network.
AB  - Global freshwater resources are under increasing pressure from economic
      development, population growth, and climate change. The international trade of
      water-intensive products (e.g., agricultural commodities) or virtual water trade
      has been suggested as a way to save water globally. We focus on the virtual water
      trade network associated with international food trade built with annual trade
      data and annual modeled virtual water content. The evolution of this network from
      1986 to 2007 is analyzed and linked to trade policies, socioeconomic
      circumstances, and agricultural efficiency. We find that the number of trade
      connections and the volume of water associated with global food trade more than
      doubled in 22 years. Despite this growth, constant organizational features were
      observed in the network. However, both regional and national virtual water trade
      patterns significantly changed. Indeed, Asia increased its virtual water imports
      by more than 170%, switching from North America to South America as its main
      partner, whereas North America oriented to a growing intraregional trade. A
      dramatic rise in China's virtual water imports is associated with its increased
      soy imports after a domestic policy shift in 2000. Significantly, this shift has
      led the global soy market to save water on a global scale, but it also relies on
      expanding soy production in Brazil, which contributes to deforestation in the
      Amazon. We find that the international food trade has led to enhanced savings in
      global water resources over time, indicating its growing efficiency in terms of
      global water use.

PMID- 22474364
TI  - Structural basis for negative cooperativity within agonist-bound TR:RXR
      heterodimers.
AB  - Thyroid hormones such as 3,3',5 triiodo-L-thyronine (T3) control numerous aspects
      of mammalian development and metabolism. The actions of such hormones are
      mediated by specific thyroid hormone receptors (TRs). TR belongs to the nuclear
      receptor family of modular transcription factors that binds to specific DNA
      response elements within target promoters. These receptors can function as homo-
      or heterodimers such as TR:9-cis retinoic acid receptor (RXR). Here, we present
      the atomic resolution structure of the TRalpha*T3:RXRalpha*9-cis retinoic acid
      (9c) ligand binding domain heterodimer complex at 2.95 A along with T3 hormone
      binding and dissociation and coactivator binding studies. Our data provide a
      structural basis for allosteric communication between T3 and 9c and negative
      cooperativity between their binding pockets. In this structure, both TR and RXR
      are in the active state conformation for optimal binding to coactivator proteins.
      However, the structure of TR*T3 within TR*T3:RXR*9c is in a relative state of
      disorder, and the observed kinetics of binding show that T3 dissociates more
      rapidly from TR*T3:RXR*9c than from TR*T3:RXR. Also, coactivator binding studies
      with a steroid receptor coactivator-1 (receptor interaction domains 1-3) fragment
      show lower affinities (K(a)) for TR*T3:RXR*9c than TR*T3:RXR. Our study
      corroborates previously reported observations from cell-based and binding studies
      and offers a structural mechanism for the repression of TR*T3:RXR transactivation
      by RXR agonists. Furthermore, the recent discoveries of multiple endogenous RXR
      agonists that mediate physiological tasks such as lipid biosynthesis underscore
      the pharmacological importance of negative cooperativity in ligand binding within
      TR:RXR heterodimers.

PMID- 22474365
TI  - RNA ligase RtcB splices 3'-phosphate and 5'-OH ends via covalent RtcB
      (histidinyl)-GMP and polynucleotide-(3')pp(5')G intermediates.
AB  - A cherished tenet of nucleic acid enzymology holds that synthesis of
      polynucleotide 3'-5' phosphodiesters proceeds via the attack of a 3'-OH on a high
      energy 5' phosphoanhydride: either a nucleoside 5'-triphosphate in the case of
      RNA/DNA polymerases or an adenylylated intermediate A(5')pp(5')N--in the case of
      polynucleotide ligases. RtcB exemplifies a family of RNA ligases implicated in
      tRNA splicing and repair. Unlike classic ligases, RtcB seals broken RNAs with 3'
      phosphate and 5'-OH ends. Here we show that RtcB executes a three-step ligation
      pathway entailing (i) reaction of His337 of the enzyme with GTP to form a
      covalent RtcB-(histidinyl-N)-GMP intermediate; (ii) transfer of guanylate to a
      polynucleotide 3'-phosphate to form a polynucleotide-(3')pp(5')G intermediate;
      and (iii) attack of a 5'-OH on the -N(3')pp(5')G end to form the splice junction.
      RtcB is structurally sui generis, and its chemical mechanism is unique. The wide
      distribution of RtcB proteins in bacteria, archaea, and metazoa raises the
      prospect of an alternative enzymology based on covalently activated 3' ends.

PMID- 22474366
TI  - Structural and mechanistic analysis of the membrane-embedded glycosyltransferase
      WaaA required for lipopolysaccharide synthesis.
AB  - WaaA is a key enzyme in the biosynthesis of LPS, a critical component of the
      outer envelope of Gram-negative bacteria. Embedded in the cytoplasmic face of the
      inner membrane, WaaA catalyzes the transfer of 3-deoxy-d-manno-oct-2-ulosonic
      acid (Kdo) to the lipid A precursor of LPS. Here we present crystal structures of
      the free and CMP-bound forms of WaaA from Aquifex aeolicus, an ancient Gram
      negative hyperthermophile. These structures reveal details of the CMP-binding
      site and implicate a unique sequence motif (GGS/TX(5)GXNXLE) in Kdo binding. In
      addition, a cluster of highly conserved amino acid residues was identified which
      represents the potential membrane-attachment and acceptor-substrate binding site
      of WaaA. A series of site-directed mutagenesis experiments revealed critical
      roles for glycine 30 and glutamate 31 in Kdo transfer. Our results provide the
      structural basis of a critical reaction in LPS biosynthesis and allowed the
      development of a detailed model of the catalytic mechanism of WaaA.

PMID- 22474368
TI  - Profile of Eric D. Siggia. Interview by Farooq Ahmed.

PMID- 22474367
TI  - Division-linked generation of death-intermediates regulates the numerical
      stability of memory CD8 T cells.
AB  - Infection or successful vaccination results in the formation of long-lived memory
      CD8 T-cell populations. Despite their numerical stability, memory CD8 T-cell
      populations are thought to completely turn over through proliferation within a 2-
      to 3-mo period. Therefore, steady-state memory cell proliferation must be
      balanced by a precisely regulated and equivalent death rate. However, the
      mechanisms regulating this balancing process remain completely undefined. Herein,
      we provide evidence for "death-intermediate memory cells" (T(DIM)) within memory
      CD8 T-cell populations generated by infection. Importantly, CD62L(Lo)/CD27(Lo)
      T(DIM)s are functionally characterized by an inability to produce cytokines, the
      failure to internalize T-cell receptor following antigenic stimulation, and
      signatures of apoptotic death. Furthermore, we demonstrate that, mechanistically,
      T(DIM) are directly generated from dividing "central memory" T-cell populations
      undergoing memory turnover in vivo. Collectively, these results demonstrate that
      as central memory CD8 T cells proliferate, they continuously generate a
      population of CD8 T cells that are nonfunctional and apoptotic; thus, our data
      support a model wherein division-linked generation of T(DIM) contributes to
      numerically stable CD8 T-cell memory.

PMID- 22474369
TI  - Relative luminance and binocular disparity preferences are correlated in macaque
      primary visual cortex, matching natural scene statistics.
AB  - Humans excel at inferring information about 3D scenes from their 2D images
      projected on the retinas, using a wide range of depth cues. One example of such
      inference is the tendency for observers to perceive lighter image regions as
      closer. This psychophysical behavior could have an ecological basis because
      nearer regions tend to be lighter in natural 3D scenes. Here, we show that an
      analogous association exists between the relative luminance and binocular
      disparity preferences of neurons in macaque primary visual cortex. The joint
      coding of relative luminance and binocular disparity at the neuronal population
      level may be an integral part of the neural mechanisms for perceptual inference
      of depth from images.

PMID- 22474370
TI  - Mouse model recapitulating human Fcgamma receptor structural and functional
      diversity.
AB  - The in vivo biological activities of IgG antibodies result from their
      bifunctional nature, in which antigen recognition by the Fab is coupled to the
      effector and immunomodulatory diversity found in the Fc domain. This diversity,
      resulting from both amino acid and glycan heterogeneity, is translated into
      cellular responses through Fcgamma receptors (FcgammaRs), a structurally and
      functionally diverse family of cell surface receptors found throughout the immune
      system. Although many of the overall features of this system are maintained
      throughout mammalian evolution, species diversity has precluded direct analysis
      of human antibodies in animal species, and, thus, detailed investigations into
      the unique features of the human IgG antibodies and their FcgammaRs have been
      limited. We now report the development of a mouse model in which all murine
      FcgammaRs have been deleted and human FcgammaRs, encoded as transgenes, have been
      inserted into the mouse genome resulting in recapitulation of the unique profile
      of human FcgammaR expression. These human FcgammaRs are shown to function to
      mediate the immunomodulatory, inflammatory, and cytotoxic activities of human IgG
      antibodies and Fc engineered variants and provide a platform for the detailed
      mechanistic analysis of therapeutic and pathogenic IgG antibodies.

PMID- 22474371
TI  - Chronic stress, glucocorticoid receptor resistance, inflammation, and disease
      risk.
AB  - We propose a model wherein chronic stress results in glucocorticoid receptor
      resistance (GCR) that, in turn, results in failure to down-regulate inflammatory
      response. Here we test the model in two viral-challenge studies. In study 1, we
      assessed stressful life events, GCR, and control variables including baseline
      antibody to the challenge virus, age, body mass index (BMI), season, race, sex,
      education, and virus type in 276 healthy adult volunteers. The volunteers were
      subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5
      d with nasal washes for viral isolation and assessment of signs/symptoms of a
      common cold. In study 2, we assessed the same control variables and GCR in 79
      subjects who were subsequently exposed to a rhinovirus and monitored at baseline
      and for 5 d after viral challenge for the production of local (in nasal
      secretions) proinflammatory cytokines (IL-1beta, TNF-alpha, and IL-6). Study 1:
      After covarying the control variables, those with recent exposure to a long-term
      threatening stressful experience demonstrated GCR; and those with GCR were at
      higher risk of subsequently developing a cold. Study 2: With the same controls
      used in study 1, greater GCR predicted the production of more local
      proinflammatory cytokines among infected subjects. These data provide support for
      a model suggesting that prolonged stressors result in GCR, which, in turn,
      interferes with appropriate regulation of inflammation. Because inflammation
      plays an important role in the onset and progression of a wide range of diseases,
      this model may have broad implications for understanding the role of stress in
      health.

PMID- 22474372
TI  - Structures of KIX domain of CBP in complex with two FOXO3a transactivation
      domains reveal promiscuity and plasticity in coactivator recruitment.
AB  - Forkhead box class O 3a (FOXO3a) is a transcription factor and tumor suppressor
      linked to longevity that determines cell fate through activating transcription of
      cell differentiation, survival, and apoptotic genes. Recruitment of the
      coactivator CBP/p300 is a crucial step in transcription, and we revealed that in
      addition to conserved region 3 (CR3) of FOXO3a, the C-terminal segment of CR2
      (CR2C) binds CBP/p300 and contributes to transcriptional activity. CR2C and CR3
      of FOXO3a interact with the KIX domain of CBP/p300 at both "MLL" and "c-Myb"
      binding sites simultaneously. A FOXO3a CR2C-CR3 peptide in complex with KIX
      exists in equilibrium between two equally populated conformational states, one of
      which has CR2C bound to the MLL site and CR3 bound to the c-Myb site, whereas in
      the other, CR2C and CR3 bind the c-Myb and MLL sites, respectively. This
      promiscuous interaction between FOXO3a and CBP/p300 is further supported by
      additional binding sites on CBP/p300, namely, the TAZ1 and TAZ2 domains. In
      functional studies, our structure-guided mutagenesis showed that both CR2C and
      CR3 are involved in the activation of certain endogenous FOXO3a target genes.
      Further, phosphorylation of S626, a known AMP-dependent protein kinase target in
      CR3, increased affinity for CBP/p300 and the phosphomimetic mutation enhanced
      transactivation of luciferase. These findings underscore the significance of
      promiscuous multivalent interactions and posttranslational modification in the
      recruitment of transcriptional coactivators, which may allow transcription
      factors to adapt to various gene-specific genomic and chromatin structures and
      respond to cell signals.

PMID- 22474373
TI  - Type II membrane protein CD69 regulates the formation of resting T-helper memory.
AB  - Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired
      immunity to eliminate infectious pathogens. We have previously demonstrated that
      most memory Th lymphocytes reside and rest on stromal niches of the bone marrow
      (BM). Little is known, however, regarding the molecular basis for the generation
      and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient
      effector CD4 T lymphocytes fail to relocate into and persist in the BM and
      therefore to differentiate into memory cells. Consequently, CD69-deficient CD4 T
      cells fail to facilitate the production of high-affinity antibodies and the
      generation of BM long-lived plasma cells in the late phase of immune responses.
      Thus, CD69 is critical for the generation and maintenance of professional memory
      Th lymphocytes, which can efficiently help humoral immunity in the late phase.
      The deficit of immunological memory in CD69-deficient mice also highlights the
      essential role of BM for the establishment of Th memory.

PMID- 22474374
TI  - Azidothymidine and other chain terminators are mutagenic for template-switch
      generated genetic mutations.
AB  - The accumulation of mutations causes cell lethality and can lead to
      carcinogenesis. An important class of mutations, which are associated with
      mutational hotspots in many organisms, are those that arise by nascent strand
      misalignment and template-switching at the site of short repetitive sequences in
      DNA. Mutagens that strongly and specifically affect this class, which is
      mechanistically distinct from other mutations that arise from polymerase errors
      or by DNA template damage, are unknown. Using Escherichia coli and assays for
      specific mutational events, this study defines such a mutagen, 3'-azidothymidine
      [zidovudine (AZT)], used widely in the treatment and prevention of HIV/AIDS. At
      sublethal doses, AZT has no significant effect on frame shifts and most base
      substitution mutations. AT-to-CG transversions and deletions at microhomologies
      were enhanced modestly by AZT. AZT strongly stimulated the "template-switch"
      class of mutations that arise in imperfect inverted repeat sequences by DNA
      strand misalignments during replication, presumably through its action as a chain
      terminator during DNA replication. Chain-terminating 2'-3'-didehydro 3'
      deoxythymidine [stavudine (D4T)] and 2'-3'-dideoxyinosine [didanosine (ddI)]
      likewise stimulated template-switch mutagenesis. These agents define a specific
      class of mutagen that promotes template-switching and acts by stalling
      replication rather than by direct nucleotide base damage.

PMID- 22474375
TI  - Profile of George M. Church.

PMID- 22474376
TI  - Evidence for a convergent slowdown in primate molecular rates and its
      implications for the timing of early primate evolution.
AB  - A long-standing problem in primate evolution is the discord between
      paleontological and molecular clock estimates for the time of crown primate
      origins: the earliest crown primate fossils are ~56 million y (Ma) old, whereas
      molecular estimates for the haplorhine-strepsirrhine split are often deep in the
      Late Cretaceous. One explanation for this phenomenon is that crown primates
      existed in the Cretaceous but that their fossil remains have not yet been found.
      Here we provide strong evidence that this discordance is better-explained by a
      convergent molecular rate slowdown in early primate evolution. We show that
      molecular rates in primates are strongly and inversely related to three life
      history correlates: body size (BS), absolute endocranial volume (EV), and
      relative endocranial volume (REV). Critically, these traits can be reconstructed
      from fossils, allowing molecular rates to be predicted for extinct primates. To
      this end, we modeled the evolutionary history of BS, EV, and REV using data from
      both extinct and extant primates. We show that the primate last common ancestor
      had a very small BS, EV, and REV. There has been a subsequent convergent increase
      in BS, EV, and REV, indicating that there has also been a convergent molecular
      rate slowdown over primate evolution. We generated a unique timescale for
      primates by predicting molecular rates from the reconstructed phenotypic values
      for a large phylogeny of living and extinct primates. This analysis suggests that
      crown primates originated close to the K-Pg boundary and possibly in the
      Paleocene, largely reconciling the molecular and fossil timescales of primate
      evolution.

PMID- 22474377
TI  - Correlated neural variability in persistent state networks.
AB  - Neural activity that persists long after stimulus presentation is a biological
      correlate of short-term memory. Variability in spiking activity causes persistent
      states to drift over time, ultimately degrading memory. Models of short-term
      memory often assume that the input fluctuations to neural populations are
      independent across cells, a feature that attenuates population-level variability
      and stabilizes persistent activity. However, this assumption is at odds with
      experimental recordings from pairs of cortical neurons showing that both the
      input currents and output spike trains are correlated. It remains unclear how
      correlated variability affects the stability of persistent activity and the
      performance of cognitive tasks that it supports. We consider the stochastic long
      timescale attractor dynamics of pairs of mutually inhibitory populations of
      spiking neurons. In these networks, persistent activity was less variable when
      correlated variability was globally distributed across both populations compared
      with the case when correlations were locally distributed only within each
      population. Using a reduced firing rate model with a continuum of persistent
      states, we show that, when input fluctuations are correlated across both
      populations, they drive firing rate fluctuations orthogonal to the persistent
      state attractor, thereby causing minimal stochastic drift. Using these insights,
      we establish that distributing correlated fluctuations globally as opposed to
      locally improves network's performance on a two-interval, delayed response
      discrimination task. Our work shows that the correlation structure of input
      fluctuations to a network is an important factor when determining long-timescale,
      persistent population spiking activity.

PMID- 22474378
TI  - Predictable and tunable half-life extension of therapeutic agents by controlled
      chemical release from macromolecular conjugates.
AB  - Conjugation to macromolecular carriers is a proven strategy for improving the
      pharmacokinetics of drugs, with many stable polyethylene glycol conjugates having
      reached the market. Stable conjugates suffer several limitations: loss of drug
      potency due to conjugation, confining the drug to the extracellular space, and
      the requirement for a circulating conjugate. Current research is directed toward
      overcoming such limitations through releasable conjugates in which the drug is
      covalently linked to the carrier through a cleavable linker. Satisfactory linkers
      that provide predictable cleavage rates tunable over a wide time range that are
      useful for both circulating and noncirculating conjugates are not yet available.
      We describe such conjugation linkers on the basis of a nonenzymatic beta
      elimination reaction with preprogrammed, highly tunable cleavage rates. A set of
      modular linkers is described that bears a succinimidyl carbonate group for
      attachment to an amine-containing drug or prodrug, an azido group for conjugation
      to the carrier, and a tunable modulator that controls the rate of beta
      eliminative cleavage. The linkers provide predictable, tunable release rates of
      ligands from macromolecular conjugates both in vitro and in vivo, with half-lives
      spanning from a range of hours to >1 y at physiological pH. A circulating PEG
      conjugate achieved a 56-fold half-life extension of the 39-aa peptide exenatide
      in rats, and a noncirculating s.c. hydrogel conjugate achieved a 150-fold
      extension. Using slow-cleaving linkers, the latter may provide a generic format
      for once-a-month dosage forms of potent drugs. The releasable linkers provide
      additional benefits that include lowering C(max) and pharmacokinetic coordination
      of drug combinations.

PMID- 22474379
TI  - Motor neurons controlling fluid ingestion in Drosophila.
AB  - Rhythmic motor behaviors such as feeding are driven by neural networks that can
      be modulated by external stimuli and internal states. In Drosophila, ingestion is
      accomplished by a pump that draws fluid into the esophagus. Here we examine how
      pumping is regulated and characterize motor neurons innervating the pump.
      Frequency of pumping is not affected by sucrose concentration or hunger but is
      altered by fluid viscosity. Inactivating motor neurons disrupts pumping and
      ingestion, whereas activating them elicits arrhythmic pumping. These motor
      neurons respond to taste stimuli and show prolonged activity to palatable
      substances. This work describes an important component of the neural circuit for
      feeding in Drosophila and is a step toward understanding the rhythmic activity
      producing ingestion.

PMID- 22474380
TI  - Mismatch repair-dependent mutagenesis in nondividing cells.
AB  - Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of
      life that removes replication errors in a strand-specific manner, such that
      mismatched nucleotides are preferentially removed from the newly replicated
      strand of DNA. Here we demonstrate a role for MMR in helping create new
      phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR
      during replication can later be subject to MMR activity in a replication strand
      independent manner in nondividing cells, resulting in either fully wild-type or
      mutant DNA sequence. In one case, this activity is responsible for what appears
      to be adaptive mutation. This replication strand-independent MMR activity could
      contribute to the formation of tumors arising in nondividing cells and could also
      contribute to mutagenesis observed during somatic hypermutation of Ig genes.

PMID- 22474381
TI  - Murine gammaherpesvirus 68 infection protects lupus-prone mice from the
      development of autoimmunity.
AB  - Gammaherpesvirus infections, such as those caused by EBV, have been suggested to
      promote the development of autoimmunity. To test this idea, we infected healthy
      WT and lupus-prone B6.Sle123 mice with an EBV-related and rodent-specific
      gammaherpesvirus, gammaHV68. Although acute gammaHV68 infection increased
      autoantibody levels for 4 to 6 wk, latent infection inhibited these responses for
      1 y. The inhibition of autoantibody expression was only observed in B6.Sle123
      females and not in males, which already displayed lower autoantibody titers.
      Contrary to the initial hypothesis, infection of young B6.Sle123 mice, both male
      and female, resulted in suppression of lymphoid activation and expansion and of
      glomerular inflammation and sclerosis, preserving kidney function. Moreover,
      gammaHV68 infection led to reduced autoantibody titers, lymphoid activation, and
      glomerular inflammation whether lupus-prone females were infected before or
      during disease manifestation. Finally, gammaHV68 infection also inhibited
      autoantibody production in the genetically distinct MRL/lpr lupus-prone mice. Our
      findings indicate that gammaHV68 infection strongly inhibits the development and
      progression of lupus-like disease in mice that spontaneously develop this
      condition mediating its beneficial effects at the humoral, cellular, and organ
      levels. The mechanisms by which the virus exerts this down-modulatory action are
      not yet clear, but appear to operate via reduced activation of dendritic cells, T
      cells, and B cells. Gammaherpesviruses coevolved with the vertebrate immune
      systems, establishing lifelong infections in humans and other mammals. Our
      findings that gammaHV68 infection prevents rather than exacerbates autoimmunity
      in mice suggest that infection with gammaherpesviruses may be protective rather
      than pathological in most individuals.

PMID- 22474382
TI  - Phosphorylation regulates human OCT4.
AB  - The transcription factor OCT4 is fundamental to maintaining pluripotency and self
      renewal. To better understand protein-level regulation of OCT4, we applied liquid
      chromatography-MS to identify 14 localized sites of phosphorylation, 11 of which
      were previously unknown. Functional analysis of two sites, T234 and S235,
      suggested that phosphorylation within the homeobox region of OCT4 negatively
      regulates its activity by interrupting sequence-specific DNA binding. Mutating
      T234 and S235 to mimic constitutive phosphorylation at these sites reduces
      transcriptional activation from an OCT4-responsive reporter and decreases
      reprogramming efficiency. We also cataloged 144 unique phosphopeptides on known
      OCT4 interacting partners, including SOX2 and SALL4, that copurified during
      immunoprecipitation. These proteins were enriched for phosphorylation at motifs
      associated with ERK signaling. Likewise, OCT4 harbored several putative ERK
      phosphorylation sites. Kinase assays confirmed that ERK2 phosphorylated these
      sites in vitro, providing a direct link between ERK signaling and the
      transcriptional machinery that governs pluripotency.

PMID- 22474383
TI  - Mutations that stabilize the open state of the Erwinia chrisanthemi ligand-gated
      ion channel fail to change the conformation of the pore domain in crystals.
AB  - The determination of structural models of the various stable states of an ion
      channel is a key step toward the characterization of its conformational dynamics.
      In the case of nicotinic-type receptors, different structures have been solved
      but, thus far, these different models have been obtained from different members
      of the superfamily. In the case of the bacterial member ELIC, a cysteamine-gated
      channel from Erwinia chrisanthemi, a structural model of the protein in the
      absence of activating ligand (and thus, conceivably corresponding to the closed
      state of this channel) has been previously generated. In this article,
      electrophysiological characterization of ELIC mutants allowed us to identify pore
      mutations that slow down the time course of desensitization to the extent that
      the channel seems not to desensitize at all for the duration of the agonist
      applications (>20 min). Thus, it seems reasonable to conclude that the
      probability of ELIC occupying the closed state is much lower for the ligand-bound
      mutants than for the unliganded wild-type channel. To gain insight into the
      conformation adopted by ELIC under these conditions, we solved the crystal
      structures of two of these mutants in the presence of a concentration of
      cysteamine that elicits an intracluster open probability of >0.9. Curiously, the
      obtained structural models turned out to be nearly indistinguishable from the
      model of the wild-type channel in the absence of bound agonist. Overall, our
      findings bring to light the limited power of functional studies in intact
      membranes when it comes to inferring the functional state of a channel in a
      crystal, at least in the case of the nicotinic-receptor superfamily.

PMID- 22474384
TI  - Properties of the human Cdc45/Mcm2-7/GINS helicase complex and its action with
      DNA polymerase epsilon in rolling circle DNA synthesis.
AB  - In eukaryotes, although the Mcm2-7 complex is a key component of the replicative
      DNA helicase, its association with Cdc45 and GINS (the CMG complex) is required
      for the activation of the DNA helicase. Here, we show that the CMG complex is
      localized to chromatin in human cells and describe the biochemical properties of
      the human CMG complex purified from baculovirus-infected Sf9 cells. The isolated
      complex binds to ssDNA regions in the presence of magnesium and ATP (or a
      nonhydrolyzable ATP analog), contains maximal DNA helicase in the presence of
      forked DNA structures, and translocates along the leading strand (3' to 5'
      direction). The complex hydrolyses ATP in the absence of DNA; unwinds duplex
      regions up to 500 bp; and either replication protein A or Escherichia coli single
      stranded binding protein increases the efficiency of displacement of long duplex
      regions. Using a 200-nt primed circular DNA substrate, the combined action of
      human DNA polymerase epsilon and the human CMG complex leads to the formation of
      products >10 kb in length. These findings suggest that the coordinated action of
      these replication complexes supports leading strand synthesis.

PMID- 22474385
TI  - Microstratigraphic evidence of in situ fire in the Acheulean strata of Wonderwerk
      Cave, Northern Cape province, South Africa.
AB  - The ability to control fire was a crucial turning point in human evolution, but
      the question when hominins first developed this ability still remains. Here we
      show that micromorphological and Fourier transform infrared microspectroscopy
      (mFTIR) analyses of intact sediments at the site of Wonderwerk Cave, Northern
      Cape province, South Africa, provide unambiguous evidence--in the form of burned
      bone and ashed plant remains--that burning took place in the cave during the
      early Acheulean occupation, approximately 1.0 Ma. To the best of our knowledge,
      this is the earliest secure evidence for burning in an archaeological context.

PMID- 22474386
TI  - Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15
      efficacy in a prostate tumor model.
AB  - IL-15 has potential as an immunotherapeutic agent for cancer treatment because of
      its ability to effectively stimulate CD8 T cell, natural killer T cell, and
      natural killer cell immunity. However, its effectiveness may be limited by
      negative immunological checkpoints that attenuate immune responses. Recently a
      clinical trial of IL-15 in cancer immunotherapy was initiated. Finding strategies
      to conquer negative regulators and enhance efficacy of IL-15 is critical and
      meaningful for such clinical trials. In a preclinical study, we evaluated IL-15
      combined with antibodies to block negative immune regulator cytotoxic T
      lymphocyte antigen 4 (CTLA-4) and programmed death ligand 1 (PD-L1) in an
      established murine transgenic adenocarcinoma of mouse prostate (TRAMP)-C2
      prostate tumor model. IL-15 treatment resulted in a significant prolongation of
      survival in tumor-bearing animals. Coadministration of anti-PD-L1 or anti-CTLA-4
      singly with IL-15 did not improve animal survival over that of IL-15 alone.
      However, simultaneous administration of IL-15 with anti-CTLA-4 and anti-PD-L1 was
      associated with increased numbers of tumor antigen-specific tetramer-positive CD8
      T cells, increased CD8 T-cell tumor lytic activity, augmented antigen-specific
      IFN-gamma release, decreased rates of tumor growth, and improved animal survival
      compared with IL-15 alone. Furthermore, triple combination therapy was associated
      with inhibition of suppressive functions of CD4(+)CD25(+) regulatory T cells and
      CD8(+)CD122(+) regulatory T cells. Thus, simultaneous blockade of CTLA-4 and PD
      L1 protected CD4 and/or CD8 T-cell activity from these regulatory T cells.
      Combining the immune stimulatory properties of IL-15 with simultaneous removal of
      two critical immune inhibitory checkpoints, we showed enhancement of immune
      responses, leading to increased antitumor activity.

PMID- 22474387
TI  - Fukushima-derived radionuclides in the ocean and biota off Japan.
AB  - The Tohoku earthquake and tsunami of March 11, 2011, resulted in unprecedented
      radioactivity releases from the Fukushima Dai-ichi nuclear power plants to the
      Northwest Pacific Ocean. Results are presented here from an international study
      of radionuclide contaminants in surface and subsurface waters, as well as in
      zooplankton and fish, off Japan in June 2011. A major finding is detection of
      Fukushima-derived (134)Cs and (137)Cs throughout waters 30-600 km offshore, with
      the highest activities associated with near-shore eddies and the Kuroshio Current
      acting as a southern boundary for transport. Fukushima-derived Cs isotopes were
      also detected in zooplankton and mesopelagic fish, and unique to this study we
      also find (110 m)Ag in zooplankton. Vertical profiles are used to calculate a
      total inventory of ~2 PBq (137)Cs in an ocean area of 150,000 km(2). Our results
      can only be understood in the context of our drifter data and an oceanographic
      model that shows rapid advection of contaminants further out in the Pacific.
      Importantly, our data are consistent with higher estimates of the magnitude of
      Fukushima fallout and direct releases [Stohl et al. (2011) Atmos Chem Phys
      Discuss 11:28319-28394; Bailly du Bois et al. (2011) J Environ Radioact,
      10.1016/j.jenvrad.2011.11.015]. We address risks to public health and marine
      biota by showing that though Cs isotopes are elevated 10-1,000* over prior levels
      in waters off Japan, radiation risks due to these radionuclides are below those
      generally considered harmful to marine animals and human consumers, and even
      below those from naturally occurring radionuclides.

PMID- 22474388
TI  - NSP4, an elastase-related protease in human neutrophils with arginine
      specificity.
AB  - Neutrophil serine proteases (NSPs) in cytoplasmic granules of neutrophils are
      regarded as important antimicrobial defense weapons after engulfment and exposure
      of pathogens to the content of primary granules. Despite intensive studies on
      neutrophils during the last three decades, only three active serine proteases,
      neutrophil elastase (NE), cathepsin G (CG), and proteinase 3 (PR3) have been
      identified in these short-lived cells. Here, we report on the identification of a
      fourth serine protease (NSP4) with 39% identity to NE and PR3, but arginine
      specificity, yet sharing features like propeptide processing by dipeptidyl
      peptidase I, storage, and release as an active enzyme with the three active
      proteases. We established monoclonal antibodies against NSP4, excluded cross
      reactivity to human granzymes, NE, CG, PR3, and azurocidin, and screened for NSP4
      protein expression in various human tissues and blood leukocyte populations. Only
      granulocyte precursors and neutrophil populations from peripheral blood were
      positive. The content of NSP4 in neutrophil lysates, however, was about 20-fold
      lower compared with CG. Upon neutrophil activation, NSP4 was released into the
      supernatant. Profiling its specificity with peptide libraries from Escherichia
      coli revealed a preference for arginine in P1; it cleaved Tyr-Arg-Phe-Arg-AMC and
      Ala-Pro-Nva-thiobenzyl esters. NSP4 was inhibited by alpha(1)-proteinase
      inhibitor (alpha(1)-antitrypsin), C1 inhibitor, and most efficiently by
      antithrombin-heparin, but not by elafin, secretory leukocyte protease inhibitor,
      alpha(1)-antichymotrypsin, and monocyte-neutrophil elastase inhibitor. Functional
      specialization and preferred natural substrates of NSP4 remain to be determined
      to understand the biological interplay of all four NSPs during neutrophil
      responses.

PMID- 22474389
TI  - Inducible NOS-induced chloride intracellular channel 4 (CLIC4) nuclear
      translocation regulates macrophage deactivation.
AB  - Nuclear translocation of cytosolic CLIC4 is an essential feature of its
      proapoptotic and prodifferentiation functions. Here we demonstrate that CLIC4 is
      induced concurrently with inducible nitric oxide synthase (iNOS) and S
      nitrosylated in proinflammatory peritoneal macrophages. Chemical inhibition or
      genetic ablation of iNOS inhibits S-nitrosylation and nuclear translocation of
      CLIC4. In macrophages, iNOS-induced nuclear CLIC4 coincides with the pro- to anti
      inflammatory transition of the cells because IL-1beta and CXCL1 mRNA remain
      elevated in CLIC4 and iNOS knockout macrophages at late time points, whereas
      TNFalpha mRNA is elevated only in the iNOS knockout macrophages. Active IL-1beta
      remains elevated in CLIC4 knockout macrophages and in macrophages in which CLIC4
      nuclear translocation is prevented by the NOS inhibitor l-NAME. Moreover,
      overexpression of nuclear-targeted CLIC4 down-regulates IL-1beta in stimulated
      macrophages. In mice, genetically null for CLIC4, the number of phagocytosing
      macrophages stimulated by LPS is reduced. Thus, iNOS-induced nuclear CLIC4 is an
      essential part of the macrophage deactivation program.

PMID- 22474390
TI  - In vivo imaging of lymphatic vessels in development, wound healing, inflammation,
      and tumor metastasis.
AB  - Lymphatic vessel growth or lymphangiogenesis occurs during embryonic development
      and wound healing and plays an important role in tumor metastasis and
      inflammatory diseases. However, the possibility of noninvasive detection and
      quantification of lymphangiogenesis has been lacking. Here, we present the
      Vegfr3(EGFPLuc) mouse model, where an EGFP-luciferase fusion protein, expressed
      under the endogenous transcriptional control of the Vegfr3 gene, allows the
      monitoring of physiological and pathological lymphangiogenesis in vivo. We show
      tracking of lymphatic vessel development during embryogenesis as well as
      lymphangiogenesis induced by specific growth factors, during wound healing and in
      contact hypersensitivity (CHS)--induced inflammation where we also monitor down
      regulation of lymphangiogenesis by the glucocorticoid dexamethasone. Importantly,
      the Vegfr3-reporter allowed us to tracking tumor-induced lymphangiogenesis at the
      tumor periphery and in lymph nodes in association with the metastatic process.
      This is the first reporter mouse model for luminescence imaging of
      lymphangiogenesis. It should provide an important tool for studying the
      involvement of lymphangiogenesis in pathological processes.

PMID- 22474391
TI  - Regulation of inflorescence architecture by intertissue layer ligand-receptor
      communication between endodermis and phloem.
AB  - Multicellular organisms achieve final body shape and size by coordinating cell
      proliferation, expansion, and differentiation. Loss of function in the
      Arabidopsis ERECTA (ER) receptor-kinase gene confers characteristic compact
      inflorescence architecture, but its underlying signaling pathways remain unknown.
      Here we report that the expression of ER in the phloem is sufficient to rescue
      compact er inflorescences. We further identified two Epidermal Patterning Factor
      like (EPFL) secreted peptide genes, EPFL4 and EPFL6/CHALLAH (CHAL), as redundant,
      upstream components of ER-mediated inflorescence growth. The expression of EPFL4
      or EPFL6 in the endodermis, a layer adjacent to phloem, is sufficient to rescue
      the er-like inflorescence of epfl4 epfl6 plants. EPFL4 and EPFL6 physically
      associate with ER in planta. Finally, transcriptome analysis of er and epfl4
      epfl6 revealed a potential downstream component as well as a role for plant
      hormones in EPFL4/6- and ER-mediated inflorescence growth. Our results suggest
      that intercell layer communication between the endodermis and phloem mediated by
      peptide ligands and a receptor kinase coordinates proper inflorescence
      architecture in Arabidopsis.

PMID- 22474392
TI  - Distinct neuropsychological subgroups in typically developing youth inform
      heterogeneity in children with ADHD.
AB  - Research and clinical investigations in psychiatry largely rely on the de facto
      assumption that the diagnostic categories identified in the Diagnostic and
      Statistical Manual (DSM) represent homogeneous syndromes. However, the
      mechanistic heterogeneity that potentially underlies the existing classification
      scheme might limit discovery of etiology for most developmental psychiatric
      disorders. Another, perhaps less palpable, reality may also be interfering with
      progress-heterogeneity in typically developing populations. In this report we
      attempt to clarify neuropsychological heterogeneity in a large dataset of
      typically developing youth and youth with attention deficit/hyperactivity
      disorder (ADHD), using graph theory and community detection. We sought to
      determine whether data-driven neuropsychological subtypes could be discerned in
      children with and without the disorder. Because individual classification is the
      sine qua non for eventual clinical translation, we also apply support vector
      machine-based multivariate pattern analysis to identify how well ADHD status in
      individual children can be identified as defined by the community detection
      delineated subtypes. The analysis yielded several unique, but similar subtypes
      across both populations. Just as importantly, comparing typically developing
      children with ADHD children within each of these distinct subgroups increased
      diagnostic accuracy. Two important principles were identified that have the
      potential to advance our understanding of typical development and developmental
      neuropsychiatric disorders. The first tenet suggests that typically developing
      children can be classified into distinct neuropsychological subgroups with high
      precision. The second tenet proposes that some of the heterogeneity in
      individuals with ADHD might be "nested" in this normal variation.

PMID- 22474393
TI  - Clusters of secretagogin-expressing neurons in the aged human olfactory tract
      lack terminal differentiation.
AB  - Expanding the repertoire of molecularly diverse neurons in the human nervous
      system is paramount to characterizing the neuronal networks that underpin sensory
      processing. Defining neuronal identities is particularly timely in the human
      olfactory system, whose structural differences from nonprimate macrosmatic
      species have recently gained momentum. Here, we identify clusters of bipolar
      neurons in a previously unknown outer "shell" domain of the human olfactory
      tract, which express secretagogin, a cytosolic Ca(2+) binding protein. These
      "shell" neurons are wired into the olfactory circuitry because they can receive
      mixed synaptic inputs. Unexpectedly, secretagogin is often coexpressed with
      polysialylated-neural cell adhesion molecule, beta-III-tubulin, and calretinin,
      suggesting that these neurons represent a cell pool that might have escaped
      terminal differentiation into the olfactory circuitry. We hypothesized that
      secretagogin-containing "shell" cells may be eliminated from the olfactory axis
      under neurodegenerative conditions. Indeed, the density, but not the
      morphological or neurochemical integrity, of secretagogin-positive neurons
      selectively decreases in the olfactory tract in Alzheimer's disease. In
      conclusion, secretagogin identifies a previously undescribed cell pool whose
      cytoarchitectonic arrangements and synaptic connectivity are poised to modulate
      olfactory processing in humans.

PMID- 22474394
TI  - Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation
      by a Legionella effector functioning in membrane trafficking.
AB  - Legionella pneumophila, the causative agent of Legionnaires' pneumonia, resides
      in a distinct vacuole structure called Legionella-containing vacuole (LCV). The
      LCV resists fusion with the lysosome and permits efficient bacterial replication
      in host macrophages, which requires a Dot/Icm type IVB secretion system. Dot/Icm
      translocated effector SdhA is critical for L. pneumophila intracellular growth
      and functions to prevent host cell death. Here, we show that the absence of SdhA
      resulted in elevated caspase-1 activation and IL-1beta secretion as well as
      macrophage pyroptosis during Legionella infection. These inflammasome activation
      phenotypes were independent of the established flagellin-NAIP5-NLRC4 axis, but
      relied on the DNA-sensing AIM2 inflammasome. We further demonstrate that
      Legionella DNA was released into macrophage cytosol, and this effect was
      significantly exaggerated by the absence of SdhA. SdhA bears a functional Golgi
      targeting GRIP domain that is required for preventing AIM2 inflammasome
      activation. Ectopically expressed SdhA formed a unique ring-shape membrane
      structure, further indicating a role in membrane trafficking and maintaining LCV
      membrane integrity. Our data together suggest a possible link, mediated by the
      function of SdhA, between LCV trafficking/maturation and suppression of host
      innate immune detection.

PMID- 22474395
TI  - Grid cells in rat entorhinal cortex encode physical space with independent firing
      fields and phase precession at the single-trial level.
AB  - When a rat moves, grid cells in its entorhinal cortex become active in multiple
      regions of the external world that form a hexagonal lattice. As the animal
      traverses one such "firing field," spikes tend to occur at successively earlier
      theta phases of the local field potential. This phenomenon is called phase
      precession. Here, we show that spike phases provide 80% more spatial information
      than spike counts and that they improve position estimates from single neurons
      down to a few centimeters. To understand what limits the resolution and how
      variable spike phases are across different field traversals, we analyze spike
      trains run by run. We find that the multiple firing fields of a grid cell operate
      as independent elements for encoding physical space. In addition, phase
      precession is significantly stronger than the pooled-run data suggest. Despite
      the inherent stochasticity of grid-cell firing, phase precession is therefore a
      robust phenomenon at the single-trial level, making a theta-phase code for
      spatial navigation feasible.

PMID- 22474397
TI  - ?
AB  - Linear kinetic Monte Carlo particle transport models are frequently employed in
      fusion plasma simulations to quantify atomic and surface effects on the main
      plasma flow dynamics. Separate codes are used for transport of neutral particles
      (incl. radiation) and charged particles (trace impurity ions). Integration of
      both modules into main plasma fluid solvers provides then self-consistent
      solutions, in principle. The required interfaces are far from trivial, because
      rapid atomic processes in particular in the edge region of fusion plasmas require
      either smoothing and resampling, or frequent transfer of particles from one into
      the other Monte Carlo code. We propose a different scheme here, in which despite
      the inherently different mathematical form of kinetic equations for ions and
      neutrals (e.g. Fokker-Planck vs. Boltzmann collision integrals) both types of
      particle orbits can be integrated into one single code. We show that the
      approximations and shortcomings of this "single sourcing" concept (e.g.,
      restriction to explicit ion drift orbit integration) can be fully tolerable in a
      wide range of typical fusion edge plasma conditions, and be overcompensated by
      the code-system simplicity, as well as by inherently ensured consistency in
      geometry (one single numerical grid only) and (the common) atomic and surface
      process modules.

PMID- 22474396
TI  - Aging impairs intermediate-term behavioral memory by disrupting the dorsal paired
      medial neuron memory trace.
AB  - How the functional activity of the brain is altered during aging to cause age
      related memory impairments is unknown. We used functional cellular imaging to
      monitor two different calcium-based memory traces that underlie olfactory
      classical conditioning in young and aged Drosophila. Functional imaging of neural
      activity in the processes of the dorsal paired medial (DPM) and mushroom body
      neurons revealed that the capacity to form an intermediate-term memory (ITM)
      trace in the DPM neurons after learning is lost with age, whereas the capacity to
      form a short-term memory trace in the alpha'/beta' mushroom body neurons remains
      unaffected by age. Stimulation of the DPM neurons by activation of a temperature
      sensitive cation channel between acquisition and retrieval enhanced ITM in aged
      but not young flies. These data indicate that the functional state of the DPM
      neurons is selectively altered with age to cause an age-related impairment of
      ITM, and demonstrate that altering the excitability of DPM neurons can restore
      age-related memory impairments.

PMID- 22474398
TI  - ?
AB  - The aim of this paper is to demonstrate that stochastic analyses can be performed
      on large and complex models within affordable costs. Stochastic analyses offer a
      much more realistic approach for analysis and design of components and systems
      although generally computationally demanding. Hence, resorting to efficient
      approaches and high performance computing is required in order to reduce the
      execution time.A general purpose software that provides an integration between
      deterministic solvers (i.e. finite element solvers), efficient algorithms for
      uncertainty management and high performance computing is presented. The software
      is intended for a wide range of applications, which includes optimization
      analysis, life-cycle management, reliability and risk analysis, fatigue and
      fractures simulation, robust design.The applicability of the proposed tools for
      practical applications is demonstrated by means of a number of case studies of
      industrial interest involving detailed models.

PMID- 22474399
TI  - Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide
      from Korean red ginseng.
AB  - Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng,
      displays immunostimulatory and antitumor activities. Even though numerous studies
      have been reported, the mechanism as to how RGAP is able to stimulate the immune
      response is not clear. In this study, we aimed to explore the mechanism of
      molecular activation of RGAP in macrophages. RGAP treatment strongly induced NO
      production in RAW264.7 cells without altering morphological changes, although the
      activity was not strong compared to LPS-induced dendritic-like morphology in
      RAW264.7 cells. RGAP-induced NO production was accompanied with enhanced mRNA
      levels of iNOS and increases in nuclear transcription factors such as NF-kappaB,
      AP-1, STAT-1, ATF-2, and CREB. According to pharmacological evaluation with
      specific enzyme inhibitors, Western blot analysis of intracellular signaling
      proteins and inhibitory pattern using blocking antibodies, ERK, and JNK were
      found to be the most important signaling enzymes compared to LPS signaling
      cascade. Further, TLR2 seems to be a target surface receptor of RGAP. Lastly,
      macrophages isolated from RGS2 knockout mice or wortmannin exposure strongly
      upregulated RGAP-treated NO production. Therefore, our results suggest that RGAP
      can activate macrophage function through activation of transcription factors such
      as NF-kappaB and AP-1 and their upstream signaling enzymes such as ERK and JNK.

PMID- 22474400
TI  - Effect of magnolol on the function of osteoblastic MC3T3-E1 cells.
AB  - OBJECTIVES: In the present study, the ability of magnolol, a hydroxylated
      biphenyl compound isolated from Magnolia officinalis, to stimulate osteoblast
      function and inhibit the release of bone-resorbing mediators was investigated in
      osteoblastic MC3T3-E1 cells. METHODS: Osteoblast function was measured by cell
      growth, alkaline phosphatase activity, collagen synthesis, and mineralization.
      Glutathione content was also measured in the cells. Bone-resorbing cytokines,
      receptor activator of nuclear factor-kappaB ligand (RANKL), TNF-alpha, and IL-6
      were measured with an enzyme immunoassay system. RESULTS: Magnolol caused a
      significant elevation of cell growth, alkaline phosphatase activity, collagen
      synthesis, mineralization, and glutathione content in the cells (P < 0.05).
      Skeletal turnover is orchestrated by a complex network of regulatory factors.
      Among cytokines, RANKL, TNF-alpha, and IL-6 were found to be key
      osteoclastogenetic molecules produced by osteoblasts. Magnolol significantly (P <
      0.05) decreased the production of osteoclast differentiation inducing factors
      such as RANKL, TNF-alpha, and IL-6 in the presence of antimycin A, which inhibits
      mitochondrial electron transport and has been used as an ROS generator.
      CONCLUSION: Magnolol might be a candidate as an agent for the prevention of bone
      disorders such as osteoporosis.

PMID- 22474401
TI  - Microalbuminuria and sRAGE in high-risk hypertensive patients treated with
      nifedipine/telmisartan combination treatment: a substudy of TALENT.
AB  - Some antihypertensive drugs have also renoprotective and anti-inflammatory
      properties that go beyond their effect on blood pressure. It has been suggested
      that microalbuminuria and glomerular filtration rate (GFR) are associated with
      circulating levels of the soluble form of the receptor, sRAGE (soluble receptor
      for advanced glycation ends-products). In the present analysis, we used data from
      the TALENT study to evaluate soluble receptor for advanced glycation end-products
      (sRAGE) plasma levels in patients with hypertension and high-cardiovascular risk
      treated nifedipine and telmisartan in combination. Treatment with nifedipine
      telmisartan significantly decreased mean systolic and diastolic ambulatory blood
      pressure and resulted in a significant increase in sRAGE plasma concentrations
      after 24 weeks of therapy. We concluded that in hypertensive patients with early
      stage renal disease, sRAGE concentrations are not influenced by either
      microalbuminuria or GFR. Long-term treatment with a combination of nifedipine
      telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus
      exerting an atheroprotective and anti-inflammatory activity.

PMID- 22474402
TI  - Peripheral mechanisms of dental pain: the role of substance P.
AB  - Current evidence supports the central role of neuropeptides in the molecular
      mechanisms underlying dental pain. In particular, substance P, a neuropeptide
      produced in neuron cell bodies localised in dorsal root and trigeminal ganglia,
      contributes to the transmission and maintenance of noxious stimuli and
      inflammatory processes. The major role of substance P in the onset of dental pain
      and inflammation is increasingly being recognised. Well-grounded experimental and
      clinical observations have documented an increase in substance P concentration in
      patients affected by caries, pulpitis, or granulomas and in those undergoing
      standard orthodontic or orthodontic/dental care procedures. This paper focuses on
      the role of substance P in the induction and maintenance of inflammation and
      dental pain, in order to define future lines of research for the evaluation of
      therapeutic strategies aimed at modulating the complex effects of this mediator
      in oral tissues.

PMID- 22474403
TI  - The valuable role of endoscopy in inflammatory bowel disease.
AB  - Endoscopy is a valuable clinical tool for the clinician who takes care of
      patients with inflammatory bowel disease (IBD). The role of endoscopy in the
      diagnosis, management, and treatment of IBD is discussed in this review. The
      central role that colonoscopy plays in screening for colon cancer in patients
      with longstanding IBD is also addressed.

PMID- 22474404
TI  - Detectability of colon polyp using computed virtual chromoendoscopy with flexible
      spectral imaging color enhancement.
AB  - The aim of this pilot study was to assess the feasibility of using computed
      virtual chromoendoscopy with the flexible spectral imaging color enhancement
      (FICE) for colon neoplasia screening. A modified back-to-back colonoscopy using
      FICE and white light in the right-sided colon was conducted prospectively for the
      consecutive patients attending for the postoperative (sigmoidectomy or anterior
      resection) follow-up colonoscopy. Histopathology of detected lesions was
      confirmed by evaluation of endoscopic resection or biopsy specimens. One-hundred
      and two patients were enrolled, and 100 patients (61 males and mean age 63 years)
      were finally analyzed. The total number of polyps detected by FICE and white
      light colonoscopy was 65 and 45, respectively. The miss rate for all polyps with
      FICE (24%) was significantly less than that with white light (46%) (P = 0.03).
      Colonoscopy using FICE could beneficially enhance the detection of neoplastic
      lesions in the right-sided colon compared to white light colonoscopy.

PMID- 22474405
TI  - Selection of marker genes using whole-genome DNA polymorphism analysis.
AB  - Molecular markers serve to assign individual samples to specific groups. Such
      markers should be easily identified and have a high discrimination power, being
      highly conserved within groups while showing sufficient variability between the
      groups that are to be distinguished. The availability of a large number of
      complete genomic sequences now enables the informed selection of genes as
      molecular markers based on the observed patterns of variability. We derived a new
      scoring system based on observed DNA polymorphic differences, and which uses the
      Bayes theorem as adapted by Wilcox. For validation, we applied this system to the
      problem of identifying individual species within a prokaryotic (Vibrio) and a
      eukaryotic (Diphyllobothrium) genus for validation. Top-scoring candidates genes
      Chromosome segregation ATPase and ATPase-subunit 6 showed better discrimination
      power in Vibrio and Diphyllobothrium, respectively, as compared to standard
      molecular markers (recA, dnaJ and atpA for Vibrio, and 18s rRNA, ITS and COX1 for
      Diphyllobothrium).

PMID- 22474406
TI  - Ureteritis cystica: important consideration in the differential diagnosis of
      acute renal colic.
AB  - Ureteritis cystica is an uncommon cause of acute renal pain. The aetiology
      remains unclear and the diagnosis may be difficult to establish. We report the
      case of a 29 year old woman with a history of repeated urinary tract infections
      presenting with acute renal colic in the absence of lithiasis. We review the
      diagnostic tools available to make the diagnosis and the recent pertinent
      literature.

PMID- 22474407
TI  - Chemical-genetic analysis of cyclin dependent kinase 2 function reveals an
      important role in cellular transformation by multiple oncogenic pathways.
AB  - A family of conserved serine/threonine kinases known as cyclin-dependent kinases
      (CDKs) drives orderly cell cycle progression in mammalian cells. Prior studies
      have suggested that CDK2 regulates S-phase entry and progression, and frequently
      shows increased activity in a wide spectrum of human tumors. Genetic KO/knockdown
      approaches, however, have suggested that lack of CDK2 protein does not prevent
      cellular proliferation, both during somatic development in mice as well as in
      human cancer cell lines. Here, we use an alternative, chemical-genetic approach
      to achieve specific inhibition of CDK2 kinase activity in cells. We directly
      compare small-molecule inhibition of CDK2 kinase activity with siRNA knockdown
      and show that small-molecule inhibition results in marked defects in
      proliferation of nontransformed cells, whereas siRNA knockdown does not,
      highlighting the differences between these two approaches. In addition, CDK2
      inhibition drastically diminishes anchorage-independent growth of human cancer
      cells and cells transformed with various oncogenes. Our results establish that
      CDK2 activity is necessary for normal mammalian cell cycle progression and
      suggest that it might be a useful therapeutic target for treating cancer.

PMID- 22474408
TI  - State-of-the-Art Management of Patients Suffering from Chronic Lymphocytic
      Leukemia.
AB  - The management of chronic lymphocytic leukemia (CLL) has evolved dramatically in
      the last decade. For the first time, clinical intervention has been shown to
      alter the natural history of the disease. Considerable efforts are focussing on
      better patient selection and response prediction, and it is expected that the
      publication of the first 200 CLL genomes will spark new insights into risk
      stratification of CLL patients. Besides, many new agents are being evaluated on
      their own and in combination therapy in early and late Phase clinical studies.
      Here, we provide a general clinical introduction into CLL including diagnosis and
      prognostic markers followed by a summary of the current state-of-the-art
      treatment. We point to areas of continued clinical research in particular for
      patients with co-morbidities and highlight the challenges in managing refractory
      disease.

PMID- 22474409
TI  - Genomewide analysis of carotenoid cleavage dioxygenases in unicellular and
      filamentous cyanobacteria.
AB  - Carotenoid cleavage dioxygenases (CCDs) are a group of enzymes that catalyze the
      oxidative cleavage steps from carotenoids to various carotenoid cleavage
      products. Some ccd genes have been identified and encoded enzymes functionally
      characterized in many higher plants, but little in cyanobacteria. We performed a
      comparative analysis of ccd sequences and explored their distribution,
      classification, phylogeny, evolution, and structure among 37 cyanobacteria.
      Totally 61 putative ccd sequences were identified, which are abundant in
      Acaryochloris marina MBIC 11017, filamentous N(2)-fixing cyanobacteria, and
      unicellular cyanobacterial Cyanothece. According to phylogenetic trees of 16S
      rDNA and CCD, nced and ccd8 genes occur later than the divergence of ccd7, apco,
      and ccd1. All CCD enzymes share conserved basic structure domains constituted by
      a single loop formed with seven beta-strands and one helix. In this paper, a
      general framework of sequence-function-evolution connection for the ccd has been
      revealed, which may provide new insight for functional investigation.

PMID- 22474410
TI  - Genotype-dependent Burst of Transposable Element Expression in Crowns of
      Hexaploid Wheat (Triticum aestivum L.) during Cold Acclimation.
AB  - The expression of 1,613 transposable elements (TEs) represented in the Affymetrix
      Wheat Genome Chip was examined during cold treatment in crowns of four hexaploid
      wheat genotypes that vary in tolerance to cold and in flowering time. The TE
      expression profiles showed a constant level of expression throughout the
      experiment in three of the genotypes. In winter Norstar, the most cold-hardy of
      the four genotypes, a subset of the TEs showed a burst of expression after
      vernalization saturation was achieved. About 47% of the TEs were expressed, and
      both Class I (retrotransposons) and Class II (DNA transposons) types were well
      represented. Gypsy and Copia were the most represented among the retrotransposons
      while CACTA and Mariner were the most represented DNA transposons. The data
      suggests that the Vrn-A1 region plays a role in the stage-specific induction of
      TE expression in this genotype.

PMID- 22474411
TI  - Features of methylation and gene expression in the promoter-associated CpG
      islands using human methylome data.
AB  - CpG islands are typically located in the 5' end of genes and considered as gene
      markers because they play important roles in gene regulation via epigenetic
      change. In this study, we compared the features of CpG islands identified by
      several major algorithms by setting the parameter cutoff values in order to
      obtain a similar number of CpG islands in a genome. This approach allows us to
      systematically compare the methylation and gene expression patterns in the
      identified CpG islands. We found that Takai and Jones' algorithm tends to
      identify longer CpG islands but with weaker CpG island features (e.g., lower GC
      content and lower ratio of the observed over expected CpGs) and higher
      methylation level. Conversely, the CpG clusters identified by Hackenberg et al.'s
      algorithm using stringent criteria are shorter and have stronger features and
      lower methylation level. In addition, we used the genome-wide base-resolution
      methylation profile in two cell lines to show that genes with a lower methylation
      level at the promoter-associated CpG islands tend to express in more tissues and
      have stronger expression. Our results validated that the DNA methylation of
      promoter-associated CpG islands suppresses gene expression at the genome level.

PMID- 22474412
TI  - ArraySearch: A Web-Based Genomic Search Engine.
AB  - Recent advances in microarray technologies have resulted in a flood of genomics
      data. This large body of accumulated data could be used as a knowledge base to
      help researchers interpret new experimental data. ArraySearch finds statistical
      correlations between newly observed gene expression profiles and the huge source
      of well-characterized expression signatures deposited in the public domain. A
      search query of a list of genes will return experiments on which the genes are
      significantly up- or downregulated collectively. Searches can also be conducted
      using gene expression signatures from new experiments. This resource will empower
      biological researchers with a statistical method to explore expression data from
      their own research by comparing it with expression signatures from a large public
      archive.

PMID- 22474413
TI  - Mutator-like elements with multiple long terminal inverted repeats in plants.
AB  - Mutator-like transposable elements (MULEs) are widespread in plants and the
      majority have long terminal inverted repeats (TIRs), which distinguish them from
      other DNA transposons. It is known that the long TIRs of Mutator elements harbor
      transposase binding sites and promoters for transcription, indicating that the
      TIR sequence is critical for transposition and for expression of sequences
      between the TIRs. Here, we report the presence of MULEs with multiple TIRs mostly
      located in tandem. These elements are detected in the genomes of maize, tomato,
      rice, and Arabidopsis. Some of these elements are present in multiple copies,
      suggesting their mobility. For those elements that have amplified, sequence
      conservation was observed for both of the tandem TIRs. For one MULE family
      carrying a gene fragment, the elements with tandem TIRs are more prevalent than
      their counterparts with a single TIR. The successful amplification of this
      particular MULE demonstrates that MULEs with tandem TIRs are functional in both
      transposition and duplication of gene sequences.

PMID- 22474414
TI  - In Silico RAPD Priming Sites in Expressed Sequences and iSCAR Markers for Oil
      Palm.
AB  - RAPD is a simple dominant marker system widely used in biology. Effectiveness of
      RAPD can be improved by selecting and redesigning primers whose priming sites
      occur in target sequence(s) of gene or organism at optimum distance. We developed
      software that uses sequences of random decamer primers and nucleotide sequence(s)
      as two input files. It locates the priming sites in input sequences and generates
      output files listing frequency and distance between priming sites. When the
      priming sites of a single primer occur more than once in a sequence with a
      distance of 200 to 2000 bp, the software also designs pairs of iSCAR primers. An
      input of 387 RAPD primers and 42,432 expressed sequences of oil palm are used as
      test. Wet-lab PCR results from a publication that used the same set of primers
      were compared with software output on priming sites. In the test sequences of oil
      palm covering 1.4% of genome, we found that at least 60% the primers chosen using
      software are sure of giving PCR amplification. We designed 641 iSCAR primers
      suitable for amplification of oil palm DNA. The software successfully predicted
      92% (67 out of 73) of published polymorphic RAPD primers in oil palm.

PMID- 22474415
TI  - The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1
      adamantyl)ammo]acetyl-2-cyanopyrrolidine] on vascular oxidative stress and
      inflammation in type 2 diabetic mice.
AB  - AIM: To investigate the combination effects and mechanisms of valsartan
      (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on
      prevention against oxidative stress and inflammation injury in db/db mice aorta.
      METHODS: Db/db mice (n = 40) were randomized to receive valsartan, LAF237,
      valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in
      diabetic mice aorta were examined. RESULTS: Valsartan or LAF237 pretreatment
      significantly increased plasma GLP-1 expression, reduced apoptosis of endothelial
      cells isolated from diabetic mice aorta. The expression of NAD(P)H oxidase
      subunits also significantly decreased resulting in decreased superoxide
      production and ICAM-1 (fold change: valsartan : 7.5 +/- 0.7, P < 0.05; LAF237:
      10.2 +/- 1.7, P < 0.05), VCAM-1 (fold change: valsartan : 5.2 +/- 1.2, P < 0.05;
      LAF237: 4.8 +/- 0.6, P < 0.05), and MCP-1 (fold change: valsartan: 3.2 +/- 0.6,
      LAF237: 4.7 +/- 0.8; P < 0.05) expression. Moreover, the combination treatment
      with valsartan and LAF237 resulted in a more significant increase of GLP-1
      expression. The decrease of the vascular oxidative stress and inflammation
      reaction was also higher than monotherapy with valsartan or LAF237. CONCLUSION:
      These data indicated that combination treatment with LAF237 and valsartan acts in
      a synergistic manner on vascular oxidative stress and inflammation in type 2
      diabetic mice.

PMID- 22474417
TI  - Experimental models of type-2 diabetic nephropathy.

PMID- 22474416
TI  - The role of glucosamine-induced ER stress in diabetic atherogenesis.
AB  - Cardiovascular disease (CVD) is the major cause of mortality in individuals with
      diabetes mellitus. However the molecular and cellular mechanisms that predispose
      individuals with diabetes to the development and progression of atherosclerosis,
      the underlying cause of most CVD, are not understood. This paper summarizes the
      current state of our knowledge of pathways and mechanisms that may link diabetes
      and hyperglycemia to atherogenesis. We highlight recent work from our lab, and
      others', that supports a role for ER stress in these processes. The continued
      investigation of existing pathways, linking hyperglycemia and diabetes mellitus
      to atherosclerosis, and the identification of novel mechanisms and targets will
      be important to the development of new and effective antiatherosclerotic
      therapies tailored to individuals with diabetes.

PMID- 22474418
TI  - L(+) and D(-) lactate are increased in plasma and urine samples of type 2
      diabetes as measured by a simultaneous quantification of L(+) and D(-) lactate by
      reversed-phase liquid chromatography tandem mass spectrometry.
AB  - BACKGROUND: Plasma and urinary levels of D-lactate have been linked to the
      presence of diabetes. Previously developed techniques have shown several
      limitations to further evaluate D-lactate as a biomarker for this condition.
      METHODS: D- and L-lactate were quantified using ultraperformance liquid
      chromatography tandem mass spectrometry with labelled internal standard. Samples
      were derivatized with diacetyl-L-tartaric anhydride and separated on a C(18)
      reversed phase column. D- and L-lactate were analysed in plasma and urine of
      controls, patients with inflammatory bowel disease (IBD), and patients with type
      2 diabetes (T2DM). RESULTS: Quantitative analysis of D- and L-lactate was
      achieved successfully. Calibration curves were linear (r(2) > 0.99) over the
      physiological and pathophysiological ranges. Recoveries for urine and plasma were
      between 96% and 113%. Inter- and intra-assay variations were between 2% and 9%.
      The limits of detection of D-lactate and L-lactate in plasma were 0.7 MUmol/L and
      0.2 MUmol/L, respectively. The limits of detection of D-lactate and L-lactate in
      urine were 8.1 nmol/mmol creatinine and 4.4 nmol/mmol creatinine, respectively.
      Plasma and urinary levels of D- and L-lactate were increased in patients with IBD
      and T2DM as compared with controls. CONCLUSION: The presented method proved to be
      suitable for the quantification of D- and L-lactate and opens the possibility to
      explore the use of D-lactate as a biomarker.

PMID- 22474419
TI  - Amelioration of glucose control mobilizes circulating pericyte progenitor cells
      in type 2 diabetic patients with microangiopathy.
AB  - Chronic diabetic complications result from an imbalance between vascular damage
      and regeneration. Several circulating lineage-committed progenitor cells have
      been implicated, but no data are available on pericyte progenitor cells (PPCs).
      Based on the evidence that PPCs increase in cancer patients after chemotherapy,
      we explored whether circulating PPC levels are affected by glucose control in
      type 2 diabetic patients, in relation to the presence of chronic complications.
      We enumerated peripheral blood PPCs as Syto16+CD45-CD31-CD140b+ events by flow
      cytometry at baseline and after 3 and 6 months of glucose control by means of add
      on basal insulin therapy on top of oral agents in 38 poorly controlled type 2
      diabetic patients. We found that, in patients with microangiopathy (n = 23), the
      level of circulating PPCs increased about 2 fold after 3 months and then returned
      to baseline at 6 months. In patients without microangiopathy (control group, n =
      15), PPCs remained fairly stable during the whole study period. No relationship
      was found between change in PPCs and macroangiopathy (either peripheral,
      coronary, or cerebrovascular). We conclude that glucose control transiently
      mobilizes PPCs diabetic patients with microangiopathy. Increase in PPCs may
      represent a vasoregenerative event or may be a consequence of ameliorated glucose
      control on microvascular lesions.

PMID- 22474420
TI  - The effects of green tea consumption on cardiometabolic alterations induced by
      experimental diabetes.
AB  - We evaluated cardiac autonomic modulation by heart rate (HRV), and arterial
      pressure variability (APV), and metabolic response in streptozotocin diabetic
      rats treated with green tea. Male Wistar rats were separated in groups: control,
      drinking tap water (C), green tea-treated (GT) group, diabetic, drinking tap
      water (D), and diabetic, treated with green tea (DGT). Kidney mass was greater in
      D and DGT than in C and GT, but reduced in DGT compared to D. Green tea prevented
      the increase in creatinine clearance and reduced hyperglycemia in DGT compared to
      D. Arterial pressure was increased in GT and decreased in D compared to C. HRV
      was reduced in D compared with all groups. APV was decreased in D compared to C
      and recovery in DGT. Sympathetic modulation of APV was decreased in D compared
      with all groups. Green tea reduced hyperglycemia, prevented renal injury and
      autonomic dysfunction, suggesting reduced cardiovascular risk and target organ
      damage in diabetes.

PMID- 22474421
TI  - TXNIP links innate host defense mechanisms to oxidative stress and inflammation
      in retinal Muller glia under chronic hyperglycemia: implications for diabetic
      retinopathy.
AB  - Thioredoxin Interacting Protein (TXNIP) mediates retinal inflammation, gliosis,
      and apoptosis in experimental diabetes. Here, we investigate the temporal
      response of Muller glia to high glucose (HG) and TXNIP expression using a rat
      Muller cell line (rMC1) in culture. We examined if HG-induced TXNIP expression
      evokes host defense mechanisms in rMC1 in response to metabolic abnormalities. HG
      causes sustained up-regulation of TXNIP (2 h to 5 days), ROS generation, ATP
      depletion, ER stress, and inflammation. Various cellular defense mechanisms are
      activated by HG: (i) NLRP3 inflammasome, (ii) ER stress response (sXBP1), (iii)
      hypoxic-like HIF-1alpha induction, (iv) autophagy/mitophagy, and (v) apoptosis.
      We also found in vivo that streptozocin-induced diabetic rats have higher retinal
      TXNIP and innate immune response gene expression than normal rats. Knock down of
      TXNIP by intravitreal siRNA reduces inflammation (IL-1beta) and gliosis (GFAP) in
      the diabetic retina. TXNIP ablation in vitro prevents ROS generation, restores
      ATP level and autophagic LC3B induction in rMC1. Thus, our results show that HG
      sustains TXNIP up-regulation in Muller glia and evokes a program of cellular
      defense/survival mechanisms that ultimately lead to oxidative stress, ER
      stress/inflammation, autophagy and apoptosis. TXNIP is a potential target to
      ameliorate blinding ocular complications of diabetic retinopathy.

PMID- 22474422
TI  - Strategies to reverse endothelial progenitor cell dysfunction in diabetes.
AB  - Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as
      the main responsible for the regulation of vascular homeostasis in adults. Since
      their discovery, endothelial progenitor cells have been depicted as mediators of
      postnatal vasculogenesis for their peculiar phenotype (partially staminal and
      partially endothelial), their ability to differentiate in endothelial cell line
      and to be incorporated into the vessels wall during ischemia/damage. Diabetes
      mellitus, a condition characterized by cardiovascular disease, nephropathy, and
      micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells.
      Herein, we review the mechanisms involved in diabetes-related dysfunction of
      endothelial progenitor cells, highlighting how hyperglycemia affects the
      different steps of endothelial progenitor cells lifetime (i.e., bone marrow
      mobilization, trafficking into the bloodstream, differentiation in endothelial
      cells, and homing in damaged tissues/organs). Finally, we review preclinical and
      clinical strategies that aim to revert diabetes-induced dysfunction of
      endothelial progenitor cells as a means of finding new strategies to prevent
      diabetic complications.

PMID- 22474423
TI  - Endothelial dysfunction in diabetes mellitus: possible involvement of endoplasmic
      reticulum stress?
AB  - The vascular complications of diabetes mellitus impose a huge burden on the
      management of this disease. The higher incidence of cardiovascular complications
      and the unfavorable prognosis among diabetic individuals who develop such
      complications have been correlated to the hyperglycemia-induced oxidative stress
      and associated endothelial dysfunction. Although antioxidants may be considered
      as effective therapeutic agents to relieve oxidative stress and protect the
      endothelium, recent clinical trials involving these agents have shown limited
      therapeutic efficacy in this regard. In the recent past experimental evidence
      suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be
      an important contributor to diabetes-related vascular complications. The current
      paper contemplates the possibility of the involvement of ER stress in endothelial
      dysfunction and diabetes-associated vascular complications.

PMID- 22474424
TI  - Endoplasmic reticulum stress and insulin biosynthesis: a review.
AB  - Insulin resistance and pancreatic beta cell dysfunction are major contributors to
      the pathogenesis of diabetes. Various conditions play a role in the pathogenesis
      of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum
      (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies
      have shown that increased ER stress induces pancreatic beta cell dysfunction and
      diabetes mellitus using genetic models of ER stress and by various stimuli. There
      are many reports indicating that ER stress plays an important role in the
      impairment of insulin biosynthesis, suggesting that reduction of ER stress could
      be a therapeutic target for diabetes. In this paper, we reviewed the relationship
      between ER stress and diabetes and how ER stress controls insulin biosynthesis.

PMID- 22474426
TI  - Links between metabolic syndrome and cardiovascular autonomic dysfunction.
AB  - BACKGROUND: Type 2 diabetes (T2D) might occur within metabolic syndrome (MbS).
      One of the complications of T2D is an impaired (imp) cardiovascular autonomic
      function (CAF). AIMS: In subjects with T2D and age <= 55 years, the prevalence of
      impCAF and its relationship with BMI, waist, HbA(1c) values, MbS, hypertension,
      and family history of T2D and/or hypertension were analysed. METHODS: 180
      subjects consecutively undergoing a day hospital for T2D were studied. The IDF
      criteria were used to diagnose MbS. To detect impCAF, 5 tests for the evaluation
      of CAF were performed with Cardionomic (Meteda, Italy). Univariate and
      multivariate analyses were performed. RESULTS: The prevalence of impCAF and MbS
      were 33.9% and 67.8%, respectively. Among diabetics with impCAF, 86.9% had MbS.
      ImpCAF was significantly associated with MbS, overweight, and HbA(1c) > 7%. Both
      logistic (P = 0.0009) and Poisson (P = 0.0113) models showed a positive
      association between impCAF and MbS. The degree of ImpCAF showed a positive linear
      correlation with BMI and HbA(1c) values. CONCLUSIONS: The study demonstrates that
      glycaemic control and overweight influence CAF and that T2D + MbS is more
      strongly associated with impCAF than isolated T2D. We suggest that MbS not only
      increases the cardiovascular risk of relatively young subjects with T2D but is
      also associated with impCAF.

PMID- 22474425
TI  - Emerging pharmacotherapies for diabetic macular edema.
AB  - Diabetic macular edema (DME) remains an important cause of visual loss in
      patients with diabetes mellitus. Although photocoagulation and intensive control
      of systemic metabolic factors have been reported to achieve improved outcomes in
      large randomized clinical trials (RCTs), some patients with DME continue to lose
      vision despite treatment. Pharmacotherapies for DME include locally and
      systemically administered agents. We review several agents that have been studied
      for the treatment of DME.

PMID- 22474427
TI  - Modulation of apoptosis pathways by oxidative stress and autophagy in beta cells.
AB  - Human islets isolated for transplantation are exposed to multiple stresses
      including oxidative stress and hypoxia resulting in significant loss of
      functional beta cell mass. In this study we examined the modulation of apoptosis
      pathway genes in islets exposed to hydrogen peroxide, peroxynitrite, hypoxia, and
      cytokines. We observed parallel induction of pro- and antiapoptotic pathways and
      identified several novel genes including BFAR, CARD8, BNIP3, and CIDE-A. As BNIP3
      is an inducer of autophagy, we examined this pathway in MIN6 cells, a mouse beta
      cell line and in human islets. Culture of MIN6 cells under low serum conditions
      increased the levels of several proteins in autophagy pathway, including ATG4,
      Beclin 1, LAMP-2, and UVRAG. Amino acid deprivation led to induction of autophagy
      in human islets. Preconditioning of islets with inducers of autophagy protected
      them from hypoxia-induced apoptosis. However, induction of autophagy during
      hypoxia exacerbated apoptotic cell death. ER stress led to induction of autophagy
      and apoptosis in beta cells. Overexpression of MnSOD, an enzyme that scavenges
      free radicals, resulted in protection of MIN6 cells from cytokine-induced
      apoptosis. Ceramide, a mediator of cytokine-induced injury, reduced the active
      phosphorylated form of Akt and downregulated the promoter activity of the
      antiapoptotic gene bcl-2. Furthermore, cytokine-stimulated JNK pathway
      downregulated the bcl-2 promoter activity which was reversed by preincubation
      with SP600125, a JNK inhibitor. Our findings suggest that beta cell apoptosis by
      multiple stresses in islets isolated for transplantation is the result of
      orchestrated gene expression in apoptosis pathway.

PMID- 22474428
TI  - Oxidative/nitrosative stress and protein damages in aqueous humor of
      hyperglycemic rabbits: effects of two oral antidiabetics, pioglitazone and
      repaglinide.
AB  - The present study was undertaken to determine oxidative/nitrosative stress in
      aqueous humor of alloxan-induced hyperglycemic rabbits and to investigate the
      effects of two oral antidiabetic drugs, pioglitazone from peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists and repaglinide from
      nonsulfonylurea K(ATP) channel blockers. Ascorbic acid (AA), glutathione (GSH),
      total antioxidant status (TAS), lipid peroxidation products (LPO), total nitrites
      (NO(2)), advanced oxidized protein products (AOPP), and protein carbonyl groups
      (PCG) were determined using respective colorimetric and ELISA methods. In our
      hyperglycemic animals, AA decreased by 77%, GSH by 45%, and TAS by 66% as
      compared to control animals. Simultaneously, LPO increased by 78%, PCG by 60%,
      AOPP by 84%, and NO(2) by 70%. In pioglitazone-treated animals, AA and TAS
      increased above control values while GSH and PCG were normalized. In turn, LPO
      was reduced by 54%, AOPP by 84%, and NO(2) by 24%, in relation to hyperglycemic
      rabbits. With repaglinide, AA and TAS were normalized, GSH increased by 20%,
      while LPO decreased by 45%. Our results show that pioglitazone and repaglinide
      differ significantly in their ability to ameliorate the parameters like NO(2),
      PCG, and AOPP. In this area, the multimodal action of pioglitazone as PPARgamma
      agonist is probably essential.

PMID- 22474430
TI  - Procalcific phenotypic drift of circulating progenitor cells in type 2 diabetes
      with coronary artery disease.
AB  - Diabetes mellitus (DM) alters circulating progenitor cells relevant for the
      pathophysiology of coronary artery disease (CAD). While endothelial progenitor
      cells (EPCs) are reduced, there is no data on procalcific polarization of
      circulating progenitors, which may contribute to vascular calcification in these
      patients. In a cohort of 107 subjects with and without DM and CAD, we analyzed
      the pro-calcific versus endothelial differentiation status of circulating CD34+
      progenitor cells. Endothelial commitment was determined by expression of VEGFR-2
      (KDR) and pro-calcific polarization by expression of osteocalcin (OC) and bone
      alkaline phosphatase (BAP). We found that DM patients had significantly higher
      expression of OC and BAP on circulating CD34+ cells than control subjects,
      especially in the presence of CAD. In patients with DM and CAD, the ratio of
      OC/KDR, BAP/KDR, and OC+BAP/KDR was about 3-fold increased than in other groups.
      EPCs cultured from DM patients with CAD occasionally formed structures highly
      suggestive of calcified nodules, and the expression of osteogenic markers by EPCs
      from control subjects was significantly increased in response to the toll-like
      receptor agonist LPS. In conclusion, circulating progenitor cells of diabetic
      patients show a phenotypic drift toward a pro-calcific phenotype that may be
      driven by inflammatory signals.

PMID- 22474429
TI  - Telomere length attrition, a marker of biological senescence, is inversely
      correlated with triglycerides and cholesterol in South Asian males with type 2
      diabetes mellitus.
AB  - South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and
      cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature
      biological ageing, assessed by reduction in telomere length (TL), may be mediated
      by factors resulting from altered metabolic profiles associated with obesity. We
      hypothesise that ethnicity and metabolic status represent detrimental factors
      contributing to premature biological ageing. Therefore we assessed TL in two
      South Asian, age and BMI-matched cohorts [T2DM (n = 142) versus non-T2DM (n =
      76)] to determine the effects of BMI, gender, lipid and CVD profile on biological
      ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and
      anthropometric data was collected and TL was measured by quantitative real-time
      PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men
      compared with non-T2DM men (P = 0.006). Additionally, in T2DM men, TL was
      inversely correlated with triglycerides and total cholesterol (r = -0.419, P <
      0.01; r = -0.443, P < 0.01). In summary, TL was reduced amongst South Asian T2DM
      men and correlated with triglycerides and total cholesterol. This study
      highlights enhanced biological ageing among South Asian, T2DM men, which appears
      to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI
      may directly contribute to premature ageing.

PMID- 22474431
TI  - Insulin resistance promotes early atherosclerosis via increased proinflammatory
      proteins and oxidative stress in fructose-fed ApoE-KO mice.
AB  - High fructose intake induces an insulin resistance state associated with
      metabolic syndrome (MS). The effect of vascular inflammation in this model is not
      completely addressed. The aim of this study was to evaluate vascular remodeling,
      inflammatory and oxidative stress markers, and atheroma development in high
      fructose diet-induced insulin resistance of ApoE-deficient mice (ApoE-KO). Mice
      were fed with either a normal chow or a 10% w/v fructose (HF) in drinking water
      over a period of 8 weeks. Thereafter, plasma metabolic parameters, vascular
      remodeling, atheroma lesion size, inflammatory markers, and NAD(P)H oxidase
      activity in the arteries were determined. HF diet induced a marked increase in
      plasma glucose, insulin, and triglycerides in ApoE-KO mice, provoked vascular
      remodeling, enhanced expression of vascular cell-adhesion molecule-1 (VCAM-1) and
      matrix metalloprotease 9 (MMP-9) and enlarged atherosclerotic lesion in aortic
      and carotid arteries. NAD(P)H oxidase activity was enhanced by fructose intake,
      and this effect was attenuated by tempol, a superoxide dismutase mimetic, and
      losartan, an Angiotensin II receptor antagonist. Our study results show that high
      fructose-induced insulin resistance promotes a proinflammatory and prooxidant
      state which accelerates atherosclerotic plaque formation in ApoE-KO mice.

PMID- 22474432
TI  - Mitochondria and endoplasmic reticulum in diabetes and its complications.

PMID- 22474433
TI  - Irritable bowel syndrome and gastrointestinal parasite infection in a developing
      nation environment.
AB  - Postinfectious IBS is defined in the industrialized world as IBS onset following
      a sentinel gastrointestinal infection. In developing nations, where repeated
      bacterial and parasitic gastrointestinal infections are common, the IBS
      pathophysiology may be altered. Our aim was to investigate the relationship
      between intestinal parasite infection and IBS in the "nonsterile" developing
      world environment. IBS subjects were identified from a population-based sample of
      1624 participants using the Rome II Modular Questionnaire. Stool samples from
      cases and randomly selected controls were examined for ova and parasites.
      Logistic regression models explored the relationship between IBS and parasite
      infection. The overall IBS prevalence among participants was 13.2% (9.3% males,
      15.9% females). There was no difference in parasite carriage between IBS cases
      and controls, 16.6% versus 15.4% (P = 0.78), nor among IBS subtypes. The
      pathophysiology of post-infectious IBS may be altered in the developing world as
      compared to industrialized nations and warrants investigation.

PMID- 22474434
TI  - The Evolution of Dieulafoy's Lesion Since 1897: Then and Now-A Journey through
      the Lens of a Pediatric Lesion with Literature Review.
AB  - Background. In 1897, Dieulafoy was the first to characterize a gaping arteriole
      within the gastric mucosa causing massive hematemesis, designating it as
      "exulceratio simplex." A hundred years later, this vascular abnormality, now
      commonly referred to as a "Dieulafoy lesion," has been identified through the
      entire gastrointestinal tract and the bronchus. Objectives and Methods. As the
      original findings have been subjected to revisions and modifications by modern
      authors, Dieulafoy's original paper was reviewed and analyzed. The evolution of
      the current usage of "Dieulafoy's lesion" in the literature has been summarized
      with comparisons to the original report. Additionally, an index case of a 10-year
      old female with a gastric "exulceratio simplex" is reported with a review of
      previously reported paediatric Dieulafoy lesions. Conclusions. The term
      "Dieulafoy lesion" in modern literature no longer adheres to the initial
      conclusions with regards to its origin, demographics, and presenting symptoms.
      Dieulafoy lesions remain a rare cause of gastrointestinal bleeding that can cause
      life-threatening haemorrhages in children.

PMID- 22474435
TI  - Gastric carcinomas localized to the cardia.
AB  - Objectives. Gastric adenocarcinomas localized to the cardia are increasing.
      Enterochromaffin-like (ECL) cells play a role in gastric carcinogenesis in
      hypergastrinemia, and the use of proton pump inhibitors (PPI) leading to
      hypergastrinemia has increased considerably during the last decades. We have
      examined cardia cancers for neuroendocrine and ECL cell differentiation. Methods.
      Thirty-two cardia cancers were examined by immunohistochemical labelling of
      chromogranin A (CgA), synaptophysin, serotonin, and histidine decarboxylase
      (HDC). Information about PPI use was collected from the patient records. Results.
      In 15 of 32 tumours, there were positive signs for one or several neuroendocrine
      markers. Five cases were CgA and serotonin positive; three of these carcinomas
      were also positive for HDC. Three patients were long-term users of PPI, and two
      of these were immunoreactive for neuroendocrine markers. Conclusions. A high
      proportion of cardia cancers expressed neuroendocrine markers, but only few
      patients with cardia cancers were using PPI.

PMID- 22474436
TI  - HIV Infection and TLR Signalling in the Liver.
AB  - Despite the availability of effective combination antiretroviral therapy (cART),
      liver disease is one of the leading causes of morbidity and mortality in Human
      Immunodeficiency Virus (HIV)-infected individuals, specifically, in the presence
      of viral hepatitis coinfection. HIV, a single stranded RNA virus, can bind to and
      activate both Toll-like receptor (TLR)7 and TLR8 in circulating blood mononuclear
      cells, but little is known about the effect of HIV on TLRs expressed in the
      liver. HIV can directly infect cells of the liver and HIV-mediated depletion of
      CD4+ T-cells in the gastrointestinal tract (GI tract) results in increased
      circulating lipopolysaccharide (LPS), both of which may impact on TLR signaling
      in the liver and subsequent liver disease progression. The potential direct and
      indirect effects of HIV on TLR signaling in the liver will be explored in this
      paper.

PMID- 22474437
TI  - Advances in Endoscopic Visualization of Barrett's Esophagus: The Role of Confocal
      Laser Endomicroscopy.
AB  - Many endoscopic imaging modalities have been developed and introduced into
      clinical practice to enhance the diagnostic capabilities of upper endoscopy. In
      the past, detection of dysplasia and carcinoma of esophagus had been dependent on
      biopsies taken during standard white-light endoscopy (WLE). Recently high
      resolution (HR) endoscopy enables us to visualize esophageal mucosa but
      resolution for glandular structures and cells is still low. Probe-based confocal
      laser endomicroscopy (pCLE) is a new promising diagnostic technique by which
      details of glandular and vascular structures of mucosal layer can be observed.
      However, the clinical utility of this new diagnostic tool has not yet been fully
      explored in a clinical setting. In this paper we will highlight this new
      technique for detection of esophageal dysplasia and carcinoma from a clinical
      practice perspective.

PMID- 22474438
TI  - Small bowel imaging in managing Crohn's disease patients.
AB  - The small bowel is essential to sustain alimentation and small bowel Crohn's
      disease (CD) may severely limit its function. Small bowel imaging is a crucial
      element in diagnosing small bowel CD, and treatment control with imaging is
      increasingly used to optimize the patients outcome. Thereby, capsule endoscopy,
      Balloon-assisted enteroscopy, and Magnetic resonance imaging have become key
      players to manage CD patients. In this review, role of small bowel imaging is
      detailed discussed for use in diagnosing and managing Crohn's disease patients.

PMID- 22474439
TI  - The efficacy and safety of endoscopic ultrasound-guided celiac plexus neurolysis
      for treatment of pain in patients with pancreatic cancer.
AB  - Introduction. Celiac plexus neurolysis is used in pain management of patients
      with advanced and unresectable pancreatic cancer. We retrospectively analyzed
      efficacy and safety of endoscopic ultrasound- (EUS-) guided celiac plexus
      neurolysis in patients treated in our unit. Methods. Twenty nine subjects with
      unresectable pancreatic cancer and severe pain despite pharmacological treatment
      underwent EUS-guided celiac plexus neurolysis with 98% ethanol. Patients scored
      their pain according to a 0-10 point scale and were interviewed 1-2 weeks and 2-3
      months after the procedure. Results. Twenty five (86%) patients reported
      improvement in their pain at 1-2 weeks following the procedure. Of these, 7 (24%)
      reported substantial improvement (decrease in pain by more than 50%) and 4 (14%)
      complete disappearance of pain. Pain relief was still present in 76% of patients
      after 2-3 months. Treatment-related side effects included hypotonia in 1 patient,
      severe pain immediately postprocedure in 2 patients, and short episodes of
      diarrhea in 3 patients. Conclusion. Endoscopic ultrasound- (EUS-) guided celiac
      plexus neurolysis is a safe and effective treatment of severe pain from advanced
      pancreatic cancer.

PMID- 22474440
TI  - Confocal Laser Endomicroscopy in the Study of Colonic Mucosa in IBD Patients: A
      Review.
AB  - Confocal laser endomicroscopy (CLE) is one of several novel methods that provide
      real-time, high-resolution imaging at a micronscale via endoscopes. CLE and
      related technologies are often termed "virtual biopsy" as they simulate the
      images seen in traditional histology. Recently, the use of CLE was reported in
      the study of colonic mucosa in patients with inflammatory bowel diseases and in
      particular in patients affected by ulcerative colitis. CLE has the potential to
      have an important role in management of IBD patients as it can be used to assess
      the grading of colitis and in detection of microscopic colitis in endoscopically
      silent segments. Moreover, CLE can be used in surveillance programs especially in
      high-risk patients. This report aims to evaluate the current data on the
      application of confocal endomicroscopy in clinical gastroenterology and
      particularly in the study of colonic mucosa in UC patients.

PMID- 22474441
TI  - Natural history of irritable bowel syndrome in women and dysmenorrhea: a 10-year
      follow-up study.
AB  - Background. Studies have shown that women are more likely to have irritable bowel
      syndrome (IBS) and more women seek healthcare because of IBS than men. Aim. We
      wanted to examine the natural history of IBS and dysmenorrhea in women over a 10
      year period and to assess the change in IBS after menopause. Method. A population
      based postal study. A questionnaire was mailed to the same age- and gender
      stratified random sample of the Icelandic population aged 18-75 in 1996 and again
      in 2006. Results. 77% premenopausal women had dysmenorrhea in the year 1996 and
      74% in 2006. 42% of women with dysmenorrhea had IBS according to Manning criteria
      in the year 2006 and 49% in 1996. 26% of women with dysmenorrhea had IBS
      according to Rome III 2006 and 11% in the year 1996. In 2006 30% women had severe
      or very severe dysmenorrhea pain severity. More women (27%) reported severe
      abdominal pain after menopause than before menopause 11%. Women without
      dysmenorrhea were twice more likely to remain asymptomatic than the women with
      dysmenorrhea. Women with dysmenorrhea were more likely to have stable symptoms
      and were twice more likely to have increased symptoms. Conclusion. Women with IBS
      are more likely to experience dysmenorrhea than women without IBS which seems to
      be a part of the symptomatology in most women with IBS. IBS symptom severity
      seems to increase after menopause.

PMID- 22474442
TI  - Predictive Value of the Model of End-Stage Liver Disease in Cirrhotic Patients
      with and without Spontaneous Bacterial Peritonitis.
AB  - Objective. We aimed to assess the predictive value of the model of end-stage
      liver disease (MELD) in hospitalized cirrhotic patients with and without
      spontaneous bacterial peritonitis (SBP) and fatal outcome. Methods. A cross
      sectional study included 256 consecutive patients (199 men and 57 women)
      diagnosed with cirrhosis and ascites who were hospitalized at the University
      Hospital Center in Tirana from January 2008 to December 2009. SBP was defined as
      a neutrophil count of >=250 cells/mm(3) in ascitic fluid. MELD score was based on
      laboratory parameters determined by UNOS Internet site MELD calculator. Results.
      In multivariable-adjusted logistic regression models controlling for age, sex,
      diabetes, and etiology, there was evidence of a positive association of SBP with
      MELD score: the odds ratio (OR) for SBP for one unit increment of MELD score was
      1.06 (95% Cl = 1.02-1.09). MELD score was significantly higher in fatal cases
      than nonfatal patients (mean age-adjusted score was 32.7 versus 18.4 overall;
      34.8 versus 18.0 in SBP patients, and 32.0 versus 18.5 in non-SBP patients; all P
      < 0.001). Conclusions. In this Albanian sample of hospitalized cirrhotic
      patients, MELD score was confirmed as a significant predictor of both SBP and
      fatal outcome.

PMID- 22474443
TI  - The epidemiology of functional gastrointestinal disorders in Mexico: a population
      based study.
AB  - Aims. The frequency of functional gastrointestinal disorders (FGIDs) in the
      general population of Mexico is unknown. Methods. To determine the prevalence of
      FGIDs, associated depression, and health care utilization, a population-based
      sampling strategy was used to select 500 households in the State of Tlaxcala, in
      central Mexico. Household interviews were conducted by two trained physicians
      using the Rome II Modular Questionnaire, a health-care and medication used
      questionnaire and the CES-D depression scale. Results. The most common FGIDs were
      IBS: 16.0% (95% CI: 12.9-19.5); functional bloating: 10.8% (8.2-13.9);
      unspecified functional bowel disorder: 10.6% (8.0-13.6); and functional
      constipation (FC): 7.4% (5.3-10.1). Uninvestigated heartburn was common: 19.6%
      (16.2-23.4). All FGIDs were equally prevalent among both genders, except for IBS
      (P = 0.001), IBS-C (P < 0.001), IBS-A/M (P = 0.049), and FC (P = 0.039) which
      were more frequent in women. Subjects with FGIDs reported higher frequencies of
      medical visits: 34.6 versus 16.8%; use of medications: 40.7 versus 21.6%; (both P
      < 0.001); and reported depression: 26.7 versus 6.7%, (P < 0.001). Conclusion. In
      this first population-based study of FGIDs in Mexico, heartburn, IBS, functional
      distension, and FC were common. Only IBS, IBS-C, IBS-A/M, and FC were more
      frequent in women. Finally, FGIDs in Mexico had an increased burden of health
      care utilization and depression.

PMID- 22474444
TI  - Reconstruction by Pancreaticogastrostomy versus Pancreaticojejunostomy following
      Pancreaticoduodenectomy: A Meta-Analysis of Randomized Controlled Trials.
AB  - Objectives. The aim of our study was to evaluate and compare the results of
      pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ) after
      pancreaticoduodenectomy (PD). Methods. Published data of randomized clinical
      trials (RCTs) comparing the clinically relevant outcomes of PG versus PJ after PD
      were analyzed. Two reviewers assessed the quality of each trial and collected
      data independently. The Cochrane Collaboration's RevMan 5.0 software was used for
      statistical analysis. Proportions were combined, and the odds ratio (OR) with its
      95% CI was used as the effect size estimate. Results. Four RCTs published in 1995
      or later were included in this meta-analysis, in which 276 patients underwent PG
      and 277 patients underwent PJ followed PD. In the combined results of PG versus
      PJ, a significant difference in the morbidity of intra-abdominal complications
      (OR, 0.34; 95% CI, 0.23-0.49; P < 0.00001) was found, but no significant
      difference could be found for pancreatic fistula (OR, 0.69; 95% CI, 0.42-1.12 , P
      = 0.13) mortality (OR, 1.09; 95% CI, 0.42-2.83; P = 0.87), recovery with no
      complications (OR, 1.26; 95% CI, 0.90-1.78; P = 0.18), biliary fistula (OR, 0.55;
      95% CI, 0.22-1.35; P = 0.19), or in delayed gastric emptying (OR, 0.55; 95% CI,
      0.33-1.01; P = 0.06). Conclusions. Current RCTs suggest that PG is better than PJ
      for pancreatic reconstruction after PD.

PMID- 22474445
TI  - Endoscopic evaluation and management of gastrointestinal bleeding in patients
      with ventricular assist devices.
AB  - The optimal diagnostic approach and yield for gastrointestinal bleeding (GIB) in
      patients with ventricular assist devices (VAD) are unknown. We explored the
      etiology of bleeding and yield of upper and lower endoscopy, balloon-assisted
      enteroscopy, and video capsule endoscopy in the evaluation of GIB in patients
      with VADs. Methods. All VAD patients with overt gastrointestinal bleeding and
      drop in hematocrit from April 1, 2000 to July 31, 2008 were retrospectively
      reviewed. The endoscopic evaluation of each episode was recorded. Overall yield
      of EGD, colonoscopy, balloon-assisted, and video capsule endoscopy were
      evaluated. Results. Thirty-six bleeding episodes occurred involving 20 patients.
      The site of GIB was identified in 32/36 episodes (88.9%), and the etiology of
      bleeding was determined in 30/36 cases (83.3%). Five VAD patients underwent VCE.
      The VCE exams demonstrated a high yield with 80% of exams identifying the
      etiology of GIB. Endoscopic intervention was successful in 8/9 attempts. No
      adverse events were recorded. Two patients required surgical intervention for
      GIB. Conclusion. Upper, lower, video capsule, and balloon-assisted enteroscopies
      are safe and demonstrate a high yield in the investigation of gastrointestinal
      bleeding in VAD patients. Medical centers caring for VAD patients should employ a
      standardized protocol to optimize endoscopic evaluation and intervention.

PMID- 22474446
TI  - Irinotecan plus mitomycin C as second-line chemotherapy for advanced gastric
      cancer resistant to fluoropyrimidine and Cisplatin: a retrospective study.
AB  - Background. S-1 plus cisplatin has been established to be standard first-line
      chemotherapy for advanced gastric cancer in Japan. The optimal second-line
      treatment refractory to S-1 plus cisplatin remains unclear. Methods. We
      retrospectively studied the efficacy, toxicity, and survival of irinotecan plus
      mitomycin C in patients with advanced gastric cancer refractory to a
      fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied.
      Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and
      docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The
      overall response rate was 17.4%. The median overall survival was 8.6 months, and
      the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities
      included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia
      (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A
      combination of irinotecan and mitomycin C is potentially effective in patients
      with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin.

PMID- 22474447
TI  - Liver disorders in inflammatory bowel disease.
AB  - Disorders of the hepatobiliary system are relatively common extraintestinal
      manifestations of inflammatory bowel disease (IBD). These disorders are sometimes
      due to a shared pathogenesis with IBD as seen in primary sclerosing cholangitis
      (PSC) and small-duct primary sclerosing cholangitis (small-duct PSC). There are
      also hepatobiliary manifestations such as cholelithiasis and portal vein
      thrombosis that occur due to the effects of chronic inflammation and the severity
      of bowel disease. Lastly, medications used in IBD such as sulfasalazine,
      thiopurines, and methotrexate can adversely affect the liver. It is important to
      be cognizant of these disorders as some do have serious long-term consequences.
      The management of these disorders often requires the expertise of
      multidisciplinary teams to achieve the best outcomes.

PMID- 22474448
TI  - Polymorphisms in HSD17B1: Early Onset and 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). In women with Down syndrome, we examined the
      relation of polymorphisms in hydroxysteroid-17beta-dehydrogenase (HSD17B1) to age
      at onset and risk of AD. HSD17B1 encodes the enzyme 17beta-hydroxysteroid
      dehydrogenase (HSD1), which catalyzes the conversion of estrone to estradiol.
      Methods. Two hundred and thirty-eight women with DS, nondemented at baseline, 31
      78 years of age, were followed at 14-18-month intervals for 4.5 years. Women were
      genotyped for 5 haplotype-tagging single-nucleotide polymorphisms (SNPs) in the
      HSD17B1 gene region, and their association with incident AD was examined.
      Results. Age at onset was earlier, and risk of AD was elevated from two- to
      threefold among women homozygous for the minor allele at 3 SNPs in intron 4
      (rs676387), exon 6 (rs605059), and exon 4 in COASY (rs598126). Carriers of the
      haplotype TCC, based on the risk alleles for these three SNPs, had an almost
      twofold increased risk of developing AD (hazard ratio = 1.8, 95% CI, 1.1-3.1).
      Conclusion. These findings support experimental and clinical studies of the
      neuroprotective role of estrogen.

PMID- 22474449
TI  - Anaplastic lymphoma kinase-positive large B-cell lymphoma: an underrecognized
      aggressive lymphoma.
AB  - Anaplastic lymphoma kinase-(ALK-) positive large B-cell lymphoma (ALK+ LBCL) is a
      rare, aggressive tumor characterized by an immunoblastic or plasmablastic
      morphologic appearance, expression of ALK, CD138, CD45, EMA, and often IgA by
      immunohistochemistry, and characteristic chromosomal translocations or
      rearrangements involving the ALK locus. The morphologic and immunophenotypic
      overlap of this tumor with other hematologic and nonhematologic malignancies may
      result in misdiagnosis. The tumor has been identified in both pediatric and adult
      populations and demonstrates a male predominance. Presentation is most often
      nodal, particularly cervical. No association with immunocompromise or geographic
      location has been recognized. The most common gene rearrangement is between
      clathrin and ALK (t(2;17)(p23;q23)), resulting in the CLTC-ALK chimeric protein,
      although other fusions have been described. Response to conventional chemotherapy
      is poor. The recent introduction of the small molecule ALK inhibitor, crizotinib,
      may provide a potential new therapeutic option for patients with this disease.

PMID- 22474450
TI  - Perceptions and experiences of women in karachi, pakistan regarding secondary
      infertility: results from a community-based qualitative study.
AB  - Background. The prevalence of infertility in Pakistan is 22% with primary
      infertility at 4% and secondary infertility at 18%. This study explored
      perceptions and experiences of women in Karachi, Pakistan regarding the causes,
      treatment-seeking behavior for and consequences of secondary infertility.
      Methods. Focus group discussions and in-depth interviews with married women
      explored their perceptions and experiences for issues related to secondary
      infertility. Results. The knowledge of women about the causes and scientific
      treatment options for infertility was limited resulting in inclination for
      traditional unsafe health care. Infertility was stated to result in marital
      instability, stigmatization and abuse specially for women with no live child.
      Conclusions. Since infertility can have a serious effect on both the
      psychological well-being and the social status of women in Pakistan, effective
      interventions are the need of the day. There is a dire need for health education
      and counseling to be integrated into infertility management plans.

PMID- 22474451
TI  - Primary tuberculosis of tonsils: a case report.
AB  - Tuberculosis is one of the major causes of ill health and death worldwide.
      Isolated tuberculosis of tonsil in the absence of active pulmonary tuberculosis
      is a very rare clinical entity. A 10-year-male child presented with recurrent
      episodes of upper respiratory tract infections, with 2-3 occurrences per month
      for the past 6 years. On general physical examination, bilateral tonsils showed
      grade III enlargement and congestion. Posterior pharyngeal wall was clear.
      Examination of the chest was within normal limits. Histopathological examination
      of bilateral tonsils revealed caseating and noncaseating epithelioid cell
      granulomas with Langhans giant cells. Ziehl-Neelsen stain for acid fast bacillus
      was positive. Features were consistent with a diagnosis of tuberculosis of
      tonsils. Tuberculosis of the oral cavity is uncommon and lesions may be either
      primary or secondary. Early detection and intervention is essential for cure.
      Isolated and primary tuberculosis of the tonsils in the absence of pulmonary
      tuberculosis is a rare entity, which prompted us to report this case.

PMID- 22474452
TI  - Concurrent cemento-osseous dysplasia and osteogenic sarcoma: report of two cases.
AB  - Aim. Cemento-osseous dysplasia (COD) represents a rare group of benign
      fibroosseous disorders, while osteogenic sarcoma (OS) on the hand, is a malignant
      tumour of ominous prognosis. A combination of COD and OS is rare and sparsely
      reported in literature. There are only four reported cases known to the authors.
      The aim of this paper is to report additional cases of COD occurring concurrently
      with OS. Materials and Methods. The clinicoradiologic findings and histological
      analysis of mandibular lesions in two patients who reported at the Dental Centre
      of the University College Hospital, Ibadan, Nigeria, are presented. Results. The
      two patients were diagnosed of mandible osteosarcoma occurring concurrently with
      bilateral mandibular focal cemento-osseous dysplasia. Conclusion. The
      simultaneous occurrence of osteosarcoma and cemento-osseous dysplasia raises the
      question of whether COD has transformed into OS or a collision tumour has
      occurred and their simultaneous occurrence is just a coincidence.

PMID- 22474453
TI  - Congenital cystic adenomatoid malformation: is there a need for pregnancy
      termination?
AB  - Aim. Congenital cystic adenomatoid lung malformation is a rare unilateral
      dysplasia of the lung. Three pathologic types are described in the literature:
      type I with cysts >2 cm, type II with cysts <1 cm, and type III with microcysts.
      The aim of this paper is to present a case of a fetus with congenital cystic
      adenomatoid lung malformation and discuss the necessity for pregnancy termination
      according to its prognosis and future mortality. Case. A 36-year-old pregnant
      woman (para: 1, gravida: 1) presented in our department for anatomy ultrasound
      screening at 20 + 1 weeks of gestation. The ultrasound detected a cystic
      adenomatoid right lung malformation measuring 1.45 * 1.67 cm which caused
      mediastinal shift of the heart and the lung to the left side. Other findings were
      cysts of the choroid plexus and echogenic intracardiac foci. The parents after
      genetic counseling decided pregnancy termination. The pregnant received
      cabergoline for ablactation. Conclusion. Congenital cystic adenomatoid lung
      malformation has different prognosis according to the type (69% in type I, 0% in
      types II and III). Fetal hydrops, cardiac and skeletal anomalies, Potter's
      syndrome, and gastrointestinal atresia are common cofindings. Genetic counseling
      is necessary, and pregnancy termination is proposed to the cases with poor
      prognosis.

PMID- 22474454
TI  - Sprengel's Deformity Associated with Musculoskeletal Dysfunctions and Renal
      Anomalies: A Case Report.
AB  - Background. Sprengel's deformity is a rare congenital anomaly of the shoulder
      girdle. The deformity is due to failure of descent of the scapula in intrauterine
      life. Case Presentation. We report a case of unilateral Sprengel's deformity
      associated with several other musculoskeletal and renal disorders consisting of
      absence of pectoralis major, weakness of trapezius and serratus anterior muscles,
      one kidney agenesis, and severe hydronephrosis of the other kidney in a 7-year
      old boy. Conclusion. Sprengel's deformity can be associated with other
      musculoskeletal abnormalities and it is much more than a cosmetic problem.

PMID- 22474455
TI  - Metastatic prostate adenocarcinoma presenting central diabetes insipidus.
AB  - The pituitary gland and infundibulum can be involved in a variety of medical
      conditions, including infiltrative diseases, fungal infections, tuberculosis, and
      primary and metastatic tumors. Metastases to the pituitary gland are absolutely
      rare, and they are generally secondary to pulmonary carcinoma in men and breast
      carcinoma in women. Pituitary metastases more commonly affect the posterior lobe
      and the infundibulum than the anterior lobe. The posterior lobe involvement may
      explain why patients with pituitary metastases frequently present with diabetes
      insipidus. We are presenting a case report of a 78-year-old male patient who had
      metastatic prostate with sudden onset of polyuria and persistent thirst. He had
      no electrolyte imbalance except mild hypernatremia. The MRI scan of the brain
      yielded a suspicious area in pituitary gland. A pituitary stalk metastasis was
      found on magnetic resonance imaging (MRI) of pituitary. Water deprivation test
      was compatible with DI. A clinical response to nasal vasopressin was achieved and
      laboratory results revealed central diabetes insipidus. As a result, the
      intrasellar and suprasellar masses decreased in size, and urinary output
      accordingly decreased.

PMID- 22474456
TI  - A Rare Cause of Lobular Panniculitis: Munchausen's Syndrome.
AB  - We describe a case of a 40-year-old woman who presented with ecchymoses of the
      right leg and who was found to have lobular panniculitis in biopsy due to
      Munchausen's Syndrome.

PMID- 22474457
TI  - Unusual cause of intestinal obstruction: left paraduodenal hernia.
AB  - Internal intestinal hernia has been defined as bulging of the intestines through
      a normal or an abnormal peritoneal or mesenteric opening. Paraduodenal hernias
      comprise 30%-53% of all internal intestinal herniations and account for 0.2%-0.9%
      of all bowel obstructions. In this paper, we aimed to present a male patient of
      42 years of age who developed intestinal obstruction due to left paraduodenal
      hernias. Left paraduodenal hernia should be taken into consideration in the
      differential diagnosis in patients of relatively younger ages with no prior
      abdominal surgery who frequently have bowel obstruction episodes.

PMID- 22474458
TI  - Coincidence of HPV11-Positive Urethral Condyloma Acuminatum and HPV-Negative
      Multiple Bladder Papillomas in a Female.
AB  - Human papillomaviruses (HPVs) are associated with proliferative lesions in a
      variety of human epithelial types. A 38-year-old female presented with a
      diagnosis of urethral condyloma acuminatum. She underwent transurethral resection
      of the urethral condyloma. At that time, multiple (five) bladder tumors were
      simultaneously found and also removed by transurethral resection. Four of the
      bladder tumors were diagnosed as squamous papilloma, and the other was urothelial
      inverted papilloma. Postoperative course was uneventful. Genomic DNA was
      extracted from 10 MUm thick sections of each bladder tumor as well as urethral
      condyloma. Then, 16 types of HPV DNA sequences were assessed with the PapiPlex
      method using genomic DNA samples extracted from each bladder tumor as well as
      urethral condyloma. HPV-11 was detected in DNA extracted from the urethral
      condyloma, while no HPV DNA sequences were positive in any of the genomic DNA
      samples extracted from the bladder tumors.

PMID- 22474459
TI  - Deep hypothermic circulatory arrest with lung perfusion/ventilation in a patient
      with acute type a aortic dissection.
AB  - A 50-year-old black male presented with acute type A aortic dissection. Surgical
      repair was performed under deep hypothermic circulatory arrest (DHCA) with lung
      perfusion/ventilation throughout the procedure. Details of the lung perfusion
      technique and its potential benefits and drawbacks are discussed.

PMID- 22474460
TI  - Torsade de Pointes and Persistent QTc Prolongation after Intravenous Amiodarone.
AB  - We report a case of torsade de pointes after intravenous amiodarone and
      concurrent hypokalemia. Despite treatment cessation and correction of electrolyte
      abnormalities, excessive QTc prolongation was noted, which persisted for 14 days.
      This prolonged course for QTc normalization may be attributed to the high rate of
      amiodarone loading and concurrent electrolyte disturbances coupled with possible
      underlying individual variability in pharmacokinetics.

PMID- 22474461
TI  - Epidemiology of astrovirus infection in children.
AB  - Human astrovirus (HAstV) is a major cause of acute diarrhea among children,
      resulting in outbreaks of diarrhea and occasionally hospitalization. Improved
      surveillance and application of sensitive molecular diagnostics have further
      defined the impact of HAstV infections in children. These studies have shown that
      HAstV infections are clinically milder (diarrhea, vomiting, fever) than
      infections with other enteric agents. Among the 8 serotypes of HAstV identified,
      serotype 1 is the predominant strain worldwide. In addition to serotype 1, the
      detection rate of HAstV types 2 to 8 has increased by using newly developed
      assays. HAstV is less common compared with other major gastroenteritis viruses,
      including norovirus and rotavirus; however, it is a potentially important viral
      etiological agent with a significant role in acute gastroenteritis. A better
      understanding of the molecular epidemiology and characteristics of HAstV strains
      may be valuable to develop specific prevention strategies.

PMID- 22474462
TI  - Diagnosis of incomplete Kawasaki disease.
AB  - Several authors suggested that the clinical characteristics of incomplete
      presentation of Kawasaki disease are similar to those of complete presentation
      and that the 2 forms of presentation are not separate entities. Based on this
      suggestion, a diagnosis of incomplete Kawasaki disease in analogy to the findings
      of complete presentation is reasonable. Currently, the diagnosis of incomplete
      Kawasaki disease might be made in cases with fewer classical diagnostic criteria
      and with several compatible clinical, laboratory or echocardiographic findings on
      the exclusion of other febrile illness. Definition of incomplete presentation in
      which coronary artery abnormalities are included as a necessary condition, is
      restrictive and specific. The validity of the diagnostic criteria of incomplete
      presentation by the American Heart Association should be thoroughly tested in the
      immediate future.

PMID- 22474463
TI  - A study of the relationship between clinical phenotypes and plasma iduronate-2
      sulfatase enzyme activities in Hunter syndrome patients.
AB  - PURPOSE: Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare
      lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS
      II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS
      activity, which is measured in leukocyte pellets or fibroblasts, was reported to
      be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of
      residual plasma IDS activity using a fluorometric assay is simpler than
      conventional measurements using skin fibroblasts or peripheral blood mononuclear
      cells. This is the first study to describe the relationship between plasma IDS
      activity and clinical phenotype of MPS II. METHODS: We hypothesized that residual
      plasma IDS activity is related to clinical phenotype. We classified 43 Hunter
      syndrome patients as having attenuated or severe disease types based on clinical
      characteristics, especially intellectual and cognitive status. There were 27
      patients with the severe type and 16 with the attenuated type. Plasma IDS
      activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl
      alpha-iduronate 2-sulphate. RESULTS: Plasma IDS activity in patients with the
      severe type was significantly lower than that in patients with the attenuated
      type (P=0.006). The optimal cut-off value of plasma IDS activity for
      distinguishing the severe type from the attenuated type was 0.63 nmol.4 hr(
      1).mL(-1). This value had 88.2% sensitivity, 65.4% specificity, and an area under
      receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis;
      P=0.003). CONCLUSION: These results show that the mild phenotype may be related
      to residual lysosomal enzyme activity.

PMID- 22474464
TI  - Hematopoietic stem cell transplantation in children with acute leukemia: similar
      outcomes in recipients of umbilical cord blood versus marrow or peripheral blood
      stem cells from related or unrelated donors.
AB  - PURPOSE: This study compared outcomes in children with acute leukemia who
      underwent transplantations with umbilical cord blood (UCB), bone marrow, or
      peripheral blood stem cells from a human leukocyte antigen (HLA)-matched related
      donor (MRD) or an unrelated donor (URD). METHODS: This retrospective study
      included consecutive acute leukemia patients who underwent their first allogeneic
      hematopoietic stem cell transplantation (HSCT) at Samsung Medical Center between
      2005 and 2010. Patients received stem cells from MRD (n=33), URD (n=46), or UCB
      (n=41). RESULTS: Neutrophil and platelet recovery were significantly longer after
      HSCT with UCB than with MRD or URD (P<0.01 for both). In multivariate analysis
      using the MRD group as a reference, the URD group had a significantly higher risk
      of grade III to IV acute graft-versus-host disease (GVHD; relative risk [RR],
      15.2; 95% confidence interval [CI], 1.2 to 186.2; P=0.03) and extensive chronic
      GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; P<0.01). For all 3 donor types, 5-year event
      free survival (EFS) and overall survival were similar. Extensive chronic GVHD was
      associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; P<0.01).
      Multivariate analysis showed that lower EFS was associated with advanced disease
      at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; P<0.01) and total body
      irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; P=0.04). CONCLUSION: Survival after UCB
      transplantation was similar to survival after MRD and URD transplantation. For
      patients lacking an HLA matched donor, the use of UCB is a suitable alternative.

PMID- 22474465
TI  - Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute
      lymphoblastic leukemia in second complete remission: a single institution study.
AB  - PURPOSE: The survival rate for childhood acute lymphoblastic leukemia (ALL) has
      improved significantly. However, overall prognosis for the 20 to 25% of patients
      who relapse is poor, and allogeneic hematopoietic stem cell transplantation
      (HSCT) offers the best chance for cure. In this study, we identified significant
      prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients
      in second complete remission (CR). METHODS: Fifty-three ALL patients (42 men,
      79%) who received HSCT in second CR from August 1991 to February 2009 were
      included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%).
      Study endpoints included cumulative incidence of acute and chronic graft-versus
      host disease (GVHD), relapse, 1-year transplant-related mortality (TRM), disease
      free survival (DFS), and overall survival (OS). RESULTS: Cumulative incidences of
      acute GVHD (grade 2 or above) and chronic GVHD were 45.3% and 28.5%,
      respectively. The estimated 5-year DFS and OS for the cohort was 45.2+/-6.8% and
      48.3+/-7%, respectively. Only donor type, i.e., sibling versus unrelated, showed
      significant correlation with DFS in multivariate analysis (P=0.010). The rates of
      relapse and 1 year TRM were 28.9+/-6.4% and 26.4+/-6.1%, respectively, and
      unrelated donor HSCT (P=0.002) and HLA mismatch (P=0.022) were significantly
      correlated with increased TRM in univariate analysis. CONCLUSION: In this single
      institution study spanning more than 17 years, sibling donor HSCT was the only
      factor predicting a favorable result in multivariate analysis, possibly due to
      increased TRM resulting from unrelated donor HSCT.

PMID- 22474466
TI  - A case of partial trisomy 3p syndrome with rare clinical manifestations.
AB  - Partial trisomy 3p results from either unbalanced translocation or de novo
      duplication. Common clinical features consist of dysmorphic facial features,
      congenital heart defects, psychomotor and mental retardation, abnormal muscle
      tone, and hypoplastic genitalia. In this paper, we report a case of partial
      trisomy 3p with rare clinical manifestations. A full-term, female newborn was
      transferred to our clinic. She had cleft lip-plate, dysgenesis of the corpus
      callosum, patent ductus arteriosus, pulmonary hypertension, and severe right
      sided hydronephrosis, associated with ureteropelvic junction obstruction.
      Cytogenetic investigation revealed partial trisomy 3p; 46,XX,der(4)t(3;4)
      (p21.1;p16). The karyotype of her father showed a balanced translocation,
      t(3;4)(p21.1;p16). Therefore, the size of duplication can be an important factor.

PMID- 22474467
TI  - A case of Hashimoto's encephalopathy presenting with seizures and psychosis.
AB  - Hashimoto's encephalopathy (HE) is a rare, poorly understood, autoimmune disease
      characterized by symptoms of acute or subacute encephalopathy associated with
      increased anti-thyroid antibody levels. Here, we report a case of a 14-year-old
      girl with HE and briefly review the literature. The patient presented with acute
      mental changes and seizures, but no evidence of infectious encephalitis. In the
      acute stage, the seizures did not respond to conventional antiepileptic drugs,
      including valproic acid, phenytoin, and topiramate. The clinical course was
      complicated by the development of acute psychosis, including bipolar mood,
      insomnia, agitation, and hallucinations. The diagnosis of HE was supported by
      positive results for antithyroperoxidase and antithyroglobulin antibodies.
      Treatment with methylprednisolone was effective; her psychosis improved and the
      number of seizures decreased. HE is a serious but curable, condition, which might
      be underdiagnosed if not suspected. Anti-thyroid antibodies must be measured for
      the diagnosis. HE should be considered in patients with diverse neuropsychiatric
      manifestations.

PMID- 22474468
TI  - Differential expression of caveolins and myosin heavy chains in response to
      forced exercise in rats.
AB  - Exercise training can improve strength and lead to adaptations in the skeletal
      muscle and nervous systems. Skeletal muscles can develop into two types: fast and
      slow, depending on the expression pattern of myosin heavy chain (MHC) isoforms.
      Previous studies reported that exercise altered the distribution of muscle fiber
      types. It is not currently known what changes in the expression of caveolins and
      types of muscle fiber occur in response to the intensity of exercise. This study
      determined the changes in expression of caveolins and MHC type after forced
      exercise in muscular and non-muscular tissues in rats. A control (Con) group to
      which forced exercise was not applied and an exercise (Ex) group to which forced
      exercise was applied. Forced exercise, using a treadmill, was introduced at a
      speed of 25 m/min for 30 min, 3 times/day (07:00, 15:00, 23:00). Homogenized
      tissues were applied to extract of total RNA for further gene analysis. The
      expression of caveolin-3 and MHC2a in the gastrocnemius muscle of female rats
      significantly increased in the Ex group compared with the Con group (P<0.05).
      Furthermore, in the gastrocnemius muscle of male rats, the expression of MHC2x
      was significantly different between the two groups (P<0.05). There was an
      increased expression in caveolin-3 and a slightly decreased expression in TGFbeta
      1 in muscular tissues implicating caveolin-3 influences the expression of MHC
      isoforms and TGFbeta-1 expression. Eventually, it implicates that caveolin-3 has
      positive regulatory function in muscle atrophy induced by neural dysfunction with
      spinal cord injury or stroke.

PMID- 22474469
TI  - Spermatotoxic effects of alpha-chlorohydrin in rats.
AB  - This study was conducted to investigate the potential effects of alpha
      chlorohydrin (ACH) on epididymal function and antioxidant system in male rats.
      The test chemical was administered to male rats by gavage at doses of 0, 3, 10,
      and 30 mg/kg/day for 7 days. Twenty-four male rats were randomly assigned to four
      experimental groups, with six rats in each group. Spermatotoxicity was assessed
      by measurement of reproductive organ weight, testicular sperm head count,
      epididymal sperm motility and morphology, histopathologic examination, and
      oxidative damage analysis in rats. At 30 mg/kg/day, an increase in the incidence
      of clinical signs, epididymis weight, and gross necropsy findings of the
      epididymis, a decrease in the sperm motility, and an increased incidence of
      histopathological changes of the epididymis were observed in a dose-dependent
      manner. At 10 mg/kg/day, an increased incidence of clinical signs and
      histopathological changes and decreased sperm motility were observed. In the
      oxidative damage analysis, an increase in the malondialdehyde concentration and a
      decrease in the glutathione content and glutathione peroxidase and catalase
      activities in the epididymal tissue were detected at >=3 mg/kg/day. The results
      show that graded doses of ACH elicit depletion of the antioxidant defense system
      and that the spermatotoxicity of ACH may be due to the induction of oxidative
      stress.

PMID- 22474470
TI  - A comparative study of the effects of topical application of Aloe vera, thyroid
      hormone and silver sulfadiazine on skin wounds in Wistar rats.
AB  - Many research studies report the healing effects of Aloe Vera, thyroid hormone
      cream and silver sulfadiazine. However, the effects of these therapeutic agents
      are not well understood and have not been compared in one study. This study aimed
      at investigating the effects of topical application of an Aloe vera gel, a
      thyroid hormone cream and a silver sulfadiazine cream on the healing of skin
      wounds surgically induced in Wistar rats for determining the treatment of choice.
      In a randomized controlled trial, twelve male rats, aged 120 days and with a mean
      weight of 250 to 300 g, were divided randomly into 5 groups based on drug
      treatments: Aloe vera gel (AV), thyroid hormone cream (TC), silver sulfadiazine
      1% (S), vehicle (V) and control. To evaluate the efficacy of each treatment
      technique, a biomechanical approach was used to assess tensile stress after 14
      days of treatment. Tensile stress was significantly improved in the Aloe vera gel
      group as compared with the other four groups (P<=0.05). While the other treatment
      options resulted in better healing than the control group, this difference was
      not significant. We conclude that Aloe vera topical application accelerated the
      healing process more than thyroid hormone, silver sulfadiazine and vehicle in
      surgically induced incisions in rats.

PMID- 22474471
TI  - Anti-obesity and anti-diabetic effects of Yerba Mate (Ilex paraguariensis) in
      C57BL/6J mice fed a high-fat diet.
AB  - Yerba Mate, derived from the leaves of the tree, Ilex paraguariensis, is widely
      used as a tea or as an ingredient in formulated foods. The aim of the present
      study was to evaluate the effects of Yerba Mate extract on weight loss, obesity
      related biochemical parameters, and diabetes in high-fat diet-fed mice.To this
      end, by using in vivo animal models of dietary-induced obesity, we have made the
      interesting observations that Yerba Mate has the ability to decrease the
      differentiation of pre-adipocytes and to reduce the accumulation of lipids in
      adipocytes, both of which contribute to a lower growth rate of adipose tissue,
      lower body weight gain, and obesity. Our data from in vivo studies revealed that
      Yerba Mate treatment affects food intake, resulting in higher energy expenditure,
      likely as a result of higher basal metabolism in Yerba Mate-treated mice.
      Furthermore, in vivo effects of Yerba Mate on lipid metabolism included
      reductions in serum cholesterol, serum triglycerides, and glucose concentrations
      in mice that were fed a high fat diet. In conclusion, Yerba Mate can potentially
      be used to treat obesity and diabetes.

PMID- 22474472
TI  - Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide
      through pancreatic lipase inhibitory activity in a rat model.
AB  - Overweight and obesity are usually related with high fat and calorie intake, and
      seriously causative of lifestyle-related diseases such as cardiovascular
      disorders, arteriosclerosis, and colon cancer. In this study, we propose a novel
      dietary therapy against overweight and obesity using mixtures of protamine and
      chitooligosaccharide (COS), which are known to interrupt the lipid metabolism in
      the body. Protamine is a dietary protein originated from salmon reproductive
      organ, and COS is an oligosaccharide made from chitin or chitosan by chemical or
      enzymatic hydrolysis. In the enzyme activity analysis in vitro, protamine and COS
      strongly suppressed the activity of pancreatic lipase, which is the primary
      enzyme for the digestion and absorption of lipids in the intestine. In in vivo
      animal test, the mixtures of protamine and COS significantly reduced the serum
      levels of triglyceride (TG), total cholesterol (T-CHO), and low density
      lipoprotein-cholesterol (LDLC) and inhibited the accumulation of lipids in liver
      tissue of Sprague Dawley (SD) rats fed high fat diets. On the other hand, they
      increased fecal TG and T-CHO contents. From these alterations in lipid
      metabolism, we verified that protamine and COS mixtures could effectively
      interrupt the digestion and absorption of dietary lipids in the body by
      inhibiting pancreatic lipase activity. In addition, protamine and COS mixtures
      increased the serum level of high density lipoprotein-cholesterol (HDLC),
      responsible for removing cholesterol from cells and protecting atherosclerosis,
      and therefore decreased the potential risks of cardiovascular diseases by
      lowering values of the atherogenic index (AI) and cardiac risk factor (CRF).
      Taken together, we suggest protamine and COS mixtures as a prominent dietary
      therapy for the prevention of overweight, obesity, and further cardiovascular
      diseases related with hyperlipidemia.

PMID- 22474473
TI  - Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light
      therapy in rabbits fed a high-cholesterol diet.
AB  - The effects of polarized-light therapy (PLT) on high-cholesterol diet (HCD)
      induced hypercholesterolemia and atherosclerosis were investigated in comparison
      with that of lovastatin in rabbits. Hypercholesterolemia was induced by feeding
      male New Zealand white rabbits with 1% cholesterol in diet for 2 weeks and
      maintained with 0.5% cholesterol for 6 weeks, followed by normal diet for 2 weeks
      for recovery. Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT on the
      outside surface of ears was started 2 weeks after induction of
      hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in
      serum cholesterol and low-density lipoproteins (LDL) levels, and finally severe
      atheromatous plaques formation covering 57.5% of the arterial walls. Lovastatin
      markedly reduced both the cholesterol and LDL, but the reducing effect (47.5%) on
      atheroma formation was relatively low. By comparison, 5-min PLT preferentially
      decreased LDL, rather than cholesterol, and thereby potentially reduced the
      atheroma area to 42.2%. Notably, 20-min PLT was superior to lovastatin in
      reducing both the cholesterol and LDL levels as well as the atheromatous plaque
      formation (26.4%). In contrast to the increases in blood alanine transaminase and
      aspartate transaminase following lovastatin treatment, PLT did not cause
      hepatotoxicity. In addition, PLT decreased platelets and hematocrit level. The
      results indicate that PLT attenuates atherosclerosis not only by lowering blood
      cholesterol and LDL levels, but also by improving blood flow without adverse
      effects. Therefore, it is suggested that PLT could be a safe alternative therapy
      for the improvement of hypercholesterolemia and atherosclerosis.

PMID- 22474474
TI  - Beneficial effects of melatonin on stroke-induced muscle atrophy in focal
      cerebral ischemic rats.
AB  - MUSCLE ATROPHY IS THE RESULT OF TWO OPPOSING CONDITIONS THAT CAN BE FOUND IN
      PATHOLOGICAL OR DISEASED MUSCLES: an imbalance in protein synthesis and
      degradation mechanisms. Thus, we investigated whether exogenous melatonin could
      regulate muscle components in stroke-induced muscle atrophy in rats. Comparing
      muscle phenotypes, we found that long-term melatonin administration could
      influence muscle mass. Muscle atrophy-related genes, including muscle atrophy F
      box (MAFbx) and muscle ring finger 1 (MuRF1) were significantly down-regulated in
      melatonin-administered rats in the gastrocnemius. However, only MAFbx at the mRNA
      level was attenuated in the soleus of melatonin-administered rats. Insulin-like
      growth factor-1 receptor (IGF-1R) was significantly over-expressed in melatonin
      administered rats in both the gastrocnemius and soleus muscles. Comparing myosin
      heavy chain (MHC) components, in the gastrocnemius, expression of both slow- and
      fast-type isoforms were significantly enhanced in melatonin-administered rats.
      These results suggest that long-term exogenous melatonin-administration may have
      a prophylactic effect on muscle atrophy through the MuRF1/MAFbx signaling
      pathway, as well as a potential therapeutic effect on muscle atrophy through the
      IGF-1-mediated hypertrophic signaling pathway in a stroke animal model.

PMID- 22474475
TI  - Anti-Helicobacter pylori effects of IgY from egg york of immunized hens.
AB  - Effects of egg york containing IgY specific for Helicobacter pylori on the
      bacterial growth and intragastric infection were investigated in comparison with
      a proton-pump inhibitor pantoprazole. For in vitro anti-bacterial activity test,
      H. pylori (1*10(8) CFU/mL) was incubated with a serially diluted IgY for 3 days.
      As a result, IgY fully inhibited the bacterial growth at 16 mg/mL, which was
      determined to a minimal inhibitory concentration. In vivo elimination study, male
      C57BL/6 mice were infected with the bacteria by intragastric inoculation (1*10(8)
      CFU/mouse) 3 times at 2-day intervals, and 2 weeks later, orally treated twice a
      day with 50, 100, 200 or 500 mg/kg IgY for 18 days. After the final
      administration, biopsy sample of the gastric mucosa was assayed for the bacterial
      identification via urease, oxidase, catalase, nitrate reduction and H(2)S tests
      in addition to microscopic examination for mucosal inflammation. In CLO kit test,
      75, 50, 12.5 and 12.5% of the animals revealed positive reaction following
      treatment with 50, 100, 200 and 500 mg/kg IgY, respectively, resulting in a
      superior efficacy at 200 mg/kg than 30 mg/kg pantoprazole that displayed 75%
      elimination. The CLO test results were confirmed by bacterial identification.
      Microscopic examination revealed that H. pylori infection caused severe gastric
      mucosal inflammation, which were not observed in the CLO-negative mice following
      treatment with IgY or pantoprazole. Taken together, IgY inhibited the growth of
      H. pylori, and improved gastritis and villi injuries by eliminating the bacteria
      from the stomach. The results indicate that IgY could be a good candidate
      overcoming tolerance of antibiotics for the treatment of H. pylori-mediated
      gastric ulcers.

PMID- 22474476
TI  - Molecular identification of Mycoplasma cynos from laboratory beagle dogs with
      respiratory disease.
AB  - In this study, we examined a colony of 20 beagle dogs in a laboratory animal
      facility. Mycoplasma was detected by consensus PCR assay in 1 dog with
      respiratory and constitutional symptoms. None of the other dogs were affected.
      The dog was euthanized and necropsied. In postmortem examinations, gray or plum
      colored gross lesions were found on the lung, most commonly in the apical and
      cardiac lobes. Some lesions showed clear demarcation and consolidation.
      Microscopic examination showed peribronchiolar lymphoid hyperplasia and
      interstitial thickening, lesions pathognomonic for mycoplasma pneumonia. To
      identify canine Mycoplasma species, we used species-specific PCR reactions for M.
      arginini, M. canis, M. cynos, M. edwardii, M. felis, M. gateae, M. maculosum, M.
      molare, M. opalescens, M. spumans, Mycoplasma sp. HRC 689, and M. collis. As the
      result, we identified Mycoplasma cynos by amplification of DNA extracted from
      lung tissue of the laboratory beagle dog with respiratory disease.

PMID- 22474477
TI  - Adiaspiromycosis of an Apodemus agrarius captured wild rodent in Korea.
AB  - Adiaspiromycosis is caused by pulmonary infection with Emmonsia. Inhalated spores
      of Emmonsia cause asymptomatic infection to necrogranulomatous pneumonia,
      depending on the burden of adiaspore and host immunity. For disease monitoring of
      wild rodents captured on Jeju Island in Korea, we examined the lung tissue of
      wild rodents histopathologically. Spores composed of thick three-layered walls
      were found following histopathological examination and were diagnosed as
      adiaspiromycosis. Adiaspiromycosis has been found in mammals in many parts of the
      world. To our knowledge, this is the first report of adiaspiromycosis of an
      Apodemus agrarius captured in Korea.

PMID- 22474478
TI  - Adaptive immune response to model antigens is impaired in murine leukocyte
      adhesion deficiency-1 revealing elevated activation thresholds in vivo.
AB  - Absence of beta2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1
      (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro
      work has established an essential function of beta2 integrins in adhesive and
      signaling properties for cells of the innate and adaptive immune system, their
      respective participation in an altered adaptive immunity in LAD1 patients are
      complex and only partly understood in vivo. Therefore, we investigated adaptive
      immune responses towards different T-dependent antigens in a murine LAD1 model of
      beta2 integrin-deficiency (CD18-/-). CD18-/- mice generated only weak IgG
      responses after immunization with tetanus toxoid (TT). In contrast, robust hapten
      and protein-specific immune responses were observed after immunization with
      highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken
      gamma globulin (NP21-CG), even though regularly structured germinal centers with
      specificity for the defined antigens/haptens in CD18-/- mice remained absent.
      However, a decrease in the hapten/protein ratio lowered the efficacy of immune
      responses in CD18-/- mice, whereas a mere reduction of the antigen dose was less
      crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a
      robust IgG response also to TT. Our findings may stimulate further studies on a
      modification of vaccination strategies using highly haptenated antigens in
      individuals suffering from LAD1.

PMID- 22474479
TI  - From murine to human nude/SCID: the thymus, T-cell development and the missing
      link.
AB  - Primary immunodeficiencies (PIDs) are disorders of the immune system, which lead
      to increased susceptibility to infections. T-cell defects, which may affect T
      cell development/function, are approximately 11% of reported PIDs. The pathogenic
      mechanisms are related to molecular alterations not only of genes selectively
      expressed in hematopoietic cells but also of the stromal component of the thymus
      that represents the primary lymphoid organ for T-cell differentiation. With this
      regard, the prototype of athymic disorders due to abnormal stroma is the
      Nude/SCID syndrome, first described in mice in 1966. In man, the DiGeorge
      Syndrome (DGS) has long been considered the human prototype of a severe T-cell
      differentiation defect. More recently, the human equivalent of the murine
      Nude/SCID has been described, contributing to unravel important issues of the T
      cell ontogeny in humans. Both mice and human diseases are due to alterations of
      the FOXN1, a developmentally regulated transcription factor selectively expressed
      in skin and thymic epithelia.

PMID- 22474480
TI  - Incomplete immune recovery in HIV infection: mechanisms, relevance for clinical
      care, and possible solutions.
AB  - Treatment of HIV-infected patients with highly active antiretroviral therapy
      (HAART) usually results in diminished viral replication, increasing CD4+ cell
      counts, a reversal of most immunological disturbances, and a reduction in risk of
      morbidity and mortality. However, approximately 20% of all HIV-infected patients
      do not achieve optimal immune reconstitution despite suppression of viral
      replication. These patients are referred to as immunological nonresponders
      (INRs). INRs present with severely altered immunological functions, including
      malfunction and diminished production of cells within lymphopoetic tissue,
      perturbed frequencies of immune regulators such as regulatory T cells and Th17
      cells, and increased immune activation, immunosenescence, and apoptosis.
      Importantly, INRs have an increased risk of morbidity and mortality compared to
      HIV-infected patients with an optimal immune reconstitution. Additional treatment
      to HAART that may improve immune reconstitution has been investigated, but
      results thus far have proved disappointing. The reason for immunological
      nonresponse is incompletely understood. This paper summarizes the known and
      unknown factors regarding the incomplete immune reconstitution in HIV infection,
      including mechanisms, relevance for clinical care, and possible solutions.

PMID- 22474482
TI  - Emergence of exhausted B cells in asymptomatic HIV-1-infected patients naive for
      HAART is related to reduced immune surveillance.
AB  - Alterations of B cell subpopulations have been described up to date as
      characterizing advanced stage of HIV-1 infection. However, whether such defects
      are relevant in subjects with a preserved number of CD4+ T cells (>350 cells/MUL)
      is unclear. In a cross-sectional study, we investigated if signs of B cells
      exhaustion and impaired viral immune surveillance are present in a cohort of 43
      asymptomatic HIV-1-infected patients with preserved CD4+ T cell counts (>350
      cells/MUL) and highly active antiretroviral therapy (HAART) untreated. A dramatic
      expansion of exhausted tissue-like memory B cells (CD10-CD21(low)CD27-) was
      observed. B cells alteration was related to an increase in Torque teno virus
      (TTV) load, used as surrogate marker of immune function. Successfully HAART
      treated patients showed normalization of B cell subpopulations frequency and TTV
      load. These results provide new insights on B cell in HIV-1 infection and show
      that development of B cell abnormalities precedes CD4+ T cell decline.

PMID- 22474481
TI  - Cellular-based immunotherapies for patients with glioblastoma multiforme.
AB  - Treatment of patients with glioblastoma multiforme (GBM) remains to be a
      challenge with a median survival of 14.6 months following diagnosis. Standard
      treatment options include surgery, radiation therapy, and systemic chemotherapy
      with temozolomide. Despite the fact that the brain constitutes an
      immunoprivileged site, recent observations after immunotherapies with lysate from
      autologous tumor cells pulsed on dendritic cells (DCs), peptides, protein,
      messenger RNA, and cytokines suggest an immunological and even clinical response
      from immunotherapies. Given this plethora of immunomodulatory therapies, this
      paper gives a structure overview of the state-of-the art in the field. Particular
      emphasis was also put on immunogenic antigens as potential targets for a more
      specific stimulation of the immune system against GBM.

PMID- 22474483
TI  - A systematic review of the epidemiology, immunopathogenesis, diagnosis, and
      treatment of pleural TB in HIV-infected patients.
AB  - BACKGROUND: High HIV burden countries have experienced a high burden of pleural
      TB in HIV-infected patients. OBJECTIVE: To review the epidemiology,
      immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected
      patients. METHODS: A literature search from 1950 to June 2011 in MEDLINE was
      conducted. RESULTS: Two-hundred and ninety-nine studies were identified, of which
      30 met the inclusion criteria. The immunopathogenesis as denoted by cells and
      cytokine profiles is distinctly different between HIV and HIV-uninfected pleural
      TB disease. Adenosine deaminase and interferon gamma are good markers of pleural
      TB disease even in HIV-infected patients. HIV-uninfected TB suspects with pleural
      effusions commonly have a low yield of TB organisms however the evidence suggests
      that in dually infected patients smear and cultures have a higher yield. The Gene
      Xpert MTB/RIF assay has significant potential to improve the diagnosis of pleural
      TB in HIV-positive patients. CONCLUSIONS: Pleural TB in HIV-infected patients has
      a different immunopathogenesis than HIV-uninfected pleural TB and these findings
      in part support the differences noted in this systematic review. Research should
      focus on developing an interferon gamma-based point of care diagnostic test and
      expansion of the role of Gene Xpert in the diagnosis of pleural TB.

PMID- 22474484
TI  - PD-L1-expressing dendritic cells contribute to viral resistance during acute HSV
      1 infection.
AB  - The inhibitory receptor, Programmed Death 1 (PD-1), and its ligands (PD-L1/PD-L2)
      are thought to play a role in immune surveillance during chronic viral infection.
      The contribution of the receptor/ligand pair during an acute infection is less
      understood. To determine the role of PD-L1 and PD-L2 during acute ocular herpes
      simplex virus type 1 (HSV-1) infection, HSV-1-infected mice administered
      neutralizing antibody to PD-L1 or PD-L2 were assessed for viral burden and host
      cellular immune responses. Virus titers were elevated in cornea and trigeminal
      ganglia (TG) of anti-PD-L1-treated mice which corresponded with a reduced number
      of CD80-expressing dendritic cells, PD-L1+ dendritic cells, and HSV-1-specific
      CD8+ T cells within the draining (mandibular) lymph node (MLN). In contrast, anti
      PD-L2 treatment had no effect on viral replication or changes in the MLN
      population. Notably, analysis of CD11c-enriched MLN cells from anti-PD-L1-treated
      mice revealed impaired functional capabilities. These studies indicate PD-L1
      expressing dendritic cells are important for antiviral defense during acute HSV-1
      infection.

PMID- 22474486
TI  - Inaccuracy of death certificate diagnosis of tuberculosis and potential
      underdiagnosis of TB in a region of high HIV prevalence.
AB  - Despite the South African antiretroviral therapy rollout, which should reduce the
      incidence of HIV-associated tuberculosis (TB), the number of TB-attributable
      deaths in KwaZuluNatal (KZN) remains high. TB is often diagnosed clinically,
      without microbiologic confirmation, leading to inaccurate estimates of TB
      attributed deaths. This may contribute to avoidable deaths, and impact population
      based TB mortality estimates. OBJECTIVES: (1) To measure the number of cases with
      microbiologically confirmed TB in a retrospective cohort of deceased inpatients
      with TB-attributed hospital deaths. (2) To estimate the rates of multi-drug
      resistant (MDR) and extensively drug resistant (XDR) TB in this cohort. RESULTS:
      Of 2752 deaths at EDH between September 2006 and March 2007, 403 (15%) were
      attributed to TB on the death certificate. 176 of the TB-attributed deaths (44%)
      had a specimen sent for smear or culture; only 64 (36%) had a TB diagnosis
      confirmed by either test. Of the 39 culture-confirmed cases, 27/39 (69%) had
      fully susceptible TB and 27/39 (69%) had smear-negative culture-positive TB
      (SNTB). Two patients had drug monoresistance, three patients had MDR-TB, and one
      had XDR-TB. CONCLUSIONS: Most TB-attributed deaths in this cohort were not
      microbiologically confirmed. Of confirmed cases, most were smear-negative,
      culture positive and were susceptible to all first line drugs.

PMID- 22474487
TI  - Immune-regulatory mechanisms in systemic autoimmune and rheumatic diseases.

PMID- 22474485
TI  - CD4+T cells: differentiation and functions.
AB  - CD4+T cells are crucial in achieving a regulated effective immune response to
      pathogens. Naive CD4+T cells are activated after interaction with antigen-MHC
      complex and differentiate into specific subtypes depending mainly on the cytokine
      milieu of the microenvironment. Besides the classical T-helper 1 and T-helper 2,
      other subsets have been identified, including T-helper 17, regulatory T cell,
      follicular helper T cell, and T-helper 9, each with a characteristic cytokine
      profile. For a particular phenotype to be differentiated, a set of cytokine
      signaling pathways coupled with activation of lineage-specific transcription
      factors and epigenetic modifications at appropriate genes are required. The
      effector functions of these cells are mediated by the cytokines secreted by the
      differentiated cells. This paper will focus on the cytokine-signaling and the
      network of transcription factors responsible for the differentiation of naive
      CD4+T cells.

PMID- 22474488
TI  - Protection against SHIV-KB9 infection by combining rDNA and rFPV vaccines based
      on HIV multiepitope and p24 protein in Chinese rhesus macaques.
AB  - Developing an effective vaccine against HIV infection remains an urgent goal. We
      used a DNA prime/fowlpox virus boost regimen to immunize Chinese rhesus macaques.
      The animals were challenged intramuscularly with pathogenic molecularly cloned
      SHIV-KB9. Immunogenicity and protective efficacy of vaccines were investigated by
      measuring IFN-gamma levels, monitoring HIV-specific binding antibodies, examining
      viral load, and analyzing CD4/CD8 ratio. Results show that, upon challenge, the
      vaccine group can induce a strong immune response in the body, represented by
      increased expression of IFN-gamma, slow and steady elevated antibody production,
      reduced peak value of acute viral load, and increase in the average CD4/CD8
      ratio. The current research suggests that rapid reaction speed, appropriate
      response strength, and long-lasting immune response time may be key protection
      factors for AIDS vaccine. The present study contributes significantly to AIDS
      vaccine and preclinical research.

PMID- 22474490
TI  - Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and
      Its Active Fraction in Human Melanoma HM3KO Cells.
AB  - The present study was to determine the anticancer potential of Labisia pumila in
      in vitro models. Results from the study revealed that ethanol extract of L.
      pumila was more cytotoxic against HM3KO cells while having reduced effects on
      nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol
      extract was selected to be further separated by using the bioassay-guided
      fractionation method to give an active fraction, SF2Lp. Results obtained from the
      flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle
      at the G1 phase, while morphological findings from AO-EB nuclear staining assays
      along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in
      HM3KO cells. Results from the mechanistic study further revealed that SF2Lp
      treatment was able to concurrently increase the expression level of p53 and pro
      apoptotic protein Bax and also reduce the expression level of anti-apoptotic
      protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2
      ratio. These findings, therefore, suggested that L. pumila was able to inhibit
      HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing
      apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein,
      mediated through a p53-dependent pathway.

PMID- 22474491
TI  - Activations of Both Extrinsic and Intrinsic Pathways in HCT 116 Human Colorectal
      Cancer Cells Contribute to Apoptosis through p53-Mediated ATM/Fas Signaling by
      Emilia sonchifolia Extract, a Folklore Medicinal Plant.
AB  - Emilia sonchifolia (L.) DC (Compositae), an herbaceous plant found in Taiwan and
      India, is used as folk medicine. The clinical applications include inflammation,
      rheumatism, cough, cuts fever, dysentery, analgesic, and antibacteria. The
      activities of Emilia sonchifolia extract (ESE) on colorectal cancer cell death
      have not been fully investigated. The purpose of this study explored the
      induction of apoptosis and its molecular mechanisms in ESE-treated HCT 116 human
      colorectal cancer cells in vitro. The methanolic ESE was characterized, and gamma
      humulene was formed as the major constituent (63.86%). ESE induced cell growth
      inhibition in a concentration- and time-dependent response by MTT assay.
      Apoptotic cells (DNA fragmentation, an apoptotic catachrestic) were found after
      ESE treatment by TUNEL assay and DNA gel electrophoresis. Alternatively, ESE
      stimulated the activities of caspase-3, -8, and -9 and their specific caspase
      inhibitors protected against ESE-induced cytotoxicity. ESE promoted the
      mitochondria-dependent and death-receptor-associated protein levels. Also, ESE
      increased ROS production and upregulated the levels of ATM, p53, and Fas in HCT
      116 cells. Strikingly, p53 siRNA reversed ESE-reduced viability involved in p53
      mediated ATM/Fas signaling in HCT 116 cells. In summary, our result is the first
      report suggesting that ESE may be potentially efficacious in the treatment of
      colorectal cancer.

PMID- 22474492
TI  - Interobserver reliability of tongue diagnosis using traditional korean medicine
      for stroke patients.
AB  - Observation of the tongue, also known as tongue diagnosis, is an important
      procedure in diagnosis by inspection in Traditional Korean medicine (TKM). We
      investigated the reliability of TKM tongue diagnosis in stroke patients by
      evaluating interobserver reliability regarding tongue indicators as part of the
      project named the Fundamental Study for the Standardization and Objectification
      of Pattern Identification in TKM for Stroke (SOPI-Stroke). A total of 658
      patients with stroke admitted to 9 oriental medical university hospitals
      participated. Each patient was independently seen by two experts from the same
      department for an examination of the status of the tongue. Interobserver
      agreement about subjects regarding pattern identification with the same opinion
      between the raters (n = 451) was generally high, ranging from "moderate" to
      "excellent". Interobserver agreement was nearly perfect for certain signs of
      special tongue appearance (mirror, spotted, and bluish purple), poor for one of
      the tongue colors (pale) and moderate for others. Clinicians displayed measurable
      agreement regarding tongue indicators via both observation and pattern
      identification consistency. However, interobserver reliability regarding tongue
      color and fur quality was relatively low. Therefore, it is necessary to improve
      objectivity and reproducibility of tongue diagnosis through the development of
      detail-oriented criteria and enhanced training of clinicians.

PMID- 22474489
TI  - scFv antibody: principles and clinical application.
AB  - To date, generation of single-chain fragment variable (scFv) has become an
      established technique used to produce a completely functional antigen-binding
      fragment in bacterial systems. The advances in antibody engineering have now
      facilitated a more efficient and generally applicable method to produce Fv
      fragments. Basically, scFv antibodies produced from phage display can be
      genetically fused to the marker proteins, such as fluorescent proteins or
      alkaline phosphatase. These bifunctional proteins having both antigen-binding
      capacity and marker activity can be obtained from transformed bacteria and used
      for one-step immunodetection of biological agents. Alternatively, antibody
      fragments could also be applied in the construction of immunotoxins, therapeutic
      gene delivery, and anticancer intrabodies for therapeutic purposes. This paper
      provides an overview of the current studies on the principle, generation, and
      application of scFv. The potential of scFv in breast cancer research is also
      discussed in this paper.

PMID- 22474493
TI  - Cordyceps militaris Grown on Germinated Soybean Induces G2/M Cell Cycle Arrest
      through Downregulation of Cyclin B1 and Cdc25c in Human Colon Cancer HT-29 Cells.
AB  - Cordyceps militaris (CM) is an insect-borne fungus that has been used in
      traditional Chinese medicine because of its wide range of pharmacological
      activities. In this paper, we studied CM grown on germinated soybean (GSC) and
      investigated the possible mechanisms underlying antiproliferative effect of GSC
      on HT-29 human colon cancer cells. In comparison with CM extracts and germinated
      soybean (GS) BuOH extracts, BuOH extracts of GSC showed remarkable inhibitory and
      antiproliferative effects on HT-29 colon cancer cells. After GSC treatment, HT-29
      cells became smaller and irregular in shape. High G2/M phase cell populations
      were observed in the GSC-treated group. The levels of cyclin B1 and Cdc25 in the
      GSC-treated group were lower than those in the control group. These findings
      suggest that GSC BuOH extracts might act as an effective anti-proliferative agent
      by inducing G2/M cell cycle arrest in colon cancer cells.

PMID- 22474494
TI  - Hypoglycemic and Hypolipidemic Effects of Ethanolic Extract of Mirabilis jalapa
      L. Root on Normal and Diabetic Mice.
AB  - The present study investigated the insulin sensitivity, hypoglycemic, and
      hypolipidemic activities of ethanolic extract of Mirabilis jalapa L. root (EEM)
      in normal and diabetic mice. After induction of diabetes with streptozotocin,
      both normal and diabetic mice were singly or repeatedly for 28 days administrated
      with EEM at doses of 2, 4, 8 g/kg, respectively. Before induction of diabetes,
      mice were administrated with EEM at doses of 2, 4, 8 g/kg for 14 days and were
      injected with streptozotocin and continued on EEM administration for another 28
      days. Both after and before induction of diabetes, repeated administration with
      4, 8 g/kg EEM continually lowered blood glucose level, decreased serum insulin
      level and improved insulin sensitivity index, and lowered serum total
      cholesterol, triglyceride levels and triglyceride content in liver and skeletal
      muscle, and increased glycogen content in these tissues; but repeated
      administration had no influence on those indexes of normal mice. Single
      administration with EEM (4, 8 g/kg) showed hypoglycemic effect in oral glucose
      tolerance test in normal and diabetic mice. Single administration with EEM had no
      hypoglycemic and hypolipidemic effects on normal and diabetic mice. These results
      suggest that EEM possesses both potential insulin sensitivity, hypoglycemic, and
      hypolipidemic effects on diabetes.

PMID- 22474495
TI  - Oreocnide integrifolia Flavonoids Augment Reprogramming for Islet Neogenesis and
      beta-Cell Regeneration in Pancreatectomized BALB/c Mice.
AB  - Agents which can either trigger proliferation of beta-cells or induce neogenesis
      of beta-cells from precursors would be of pivotal role in reversing diabetic
      manifestations. We examined the role of flavonoid rich fraction (FRF) of
      Oreocnide integrifolia leaves using a mice model of experimental regeneration.
      BALB/c mice were subjected to ~70% pancreatectomy (Px) and supplemented with FRF
      for 7, 14, and 21 days after pancreatectomy. Px animals displayed increased blood
      glucose levels and decreased insulin titres which were ameliorated by FRF
      supplementation. FRF-treated mice demonstrated prominent newly formed islets
      budding off from ducts and depicting increased BrdU incorporation. Additionally,
      transcripts levels of Ins1/2, Reg-3alpha/gamma, Ngn-3, and Pdx-1 were upregulated
      during the initial 1 week. The present study provides evidence of a nutraceutical
      contributing to islet neogenesis from ductal cells as the mode of beta-cell
      regeneration and a potential therapeutic for clinical trials in management of
      diabetic manifestations.

PMID- 22474496
TI  - Ethnopharmacology of medicinal plants of the pantanal region (mato grosso,
      Brazil).
AB  - Traditional knowledge is an important source of obtaining new phytotherapeutic
      agents. Ethnobotanical survey of medicinal plants was conducted in Nossa Senhora
      Aparecida do Chumbo District (NSACD), located in Pocone, Mato Grosso, Brazil
      using semi-structured questionnaires and interviews. 376 species of medicinal
      plants belonging to 285 genera and 102 families were cited. Fabaceae (10.2%),
      Asteraceae (7.82%) and Lamaceae (4.89%) families are of greater importance.
      Species with the greater relative importance were Himatanthus obovatus (1.87),
      Hibiscus sabdariffa (1.87), Solidago microglossa (1.80), Strychnos pseudoquina
      (1.73) and Dorstenia brasiliensis, Scoparia dulcis L., and Luehea divaricata
      (1.50). The informant consensus factor (ICF) ranged from 0.13 to 0.78
      encompassing 18 disease categories,of which 15 had ICF greater than 0.50, with a
      predominance of disease categories related to injuries, poisoning and certain
      other consequences of external causes (ICF  =  0.78) having 65 species cited
      while 20 species were cited for mental and behavioral disorders (ICF  =  0.77).
      The results show that knowledge about medicinal plants is evenly distributed
      among the population of NSACD. This population possesses medicinal plants for
      most disease categories, with the highest concordance for prenatal,
      mental/behavioral and respiratory problems.

PMID- 22474497
TI  - The Effects of a Gentle Yoga Program on Sleep, Mood, and Blood Pressure in Older
      Women with Restless Legs Syndrome (RLS): A Preliminary Randomized Controlled
      Trial.
AB  - Objective. To examine the effects of yoga versus an educational film program on
      sleep, mood, perceived stress, and sympathetic activation in older women with
      RLS. Methods. Participants were drawn from a larger trial regarding the effects
      of yoga on cardiovascular disease risk profiles in overweight, sedentary
      postmenopausal women. Seventy-five women were randomized to receive either an 8
      week yoga (n = 38) or educational film (n = 37) program. All 75 participants
      completed an RLS screening questionnaire. The 20 women who met all four
      diagnostic criteria for RLS (n = 10 yoga, 10 film group) comprised the population
      for this nested study. Main outcomes assessed pre- and post-treatment included:
      sleep (Pittsburgh Sleep Quality Index), stress (Perceived Stress Scale), mood
      (Profile of Mood States, State-Trait Anxiety Inventory), blood pressure, and
      heart rate. Results. The yoga group demonstrated significantly greater
      improvements than controls in multiple domains of sleep quality and mood, and
      significantly greater reductions in insomnia prevalence, anxiety, perceived
      stress, and blood pressure (all P's<=0.05). Adjusted intergroup effect sizes for
      psychosocial variables were large, ranging from 1.9 for state anxiety to 2.6 for
      sleep quality. Conclusions. These preliminary findings suggest yoga may offer an
      effective intervention for improving sleep, mood, perceived stress, and blood
      pressure in older women with RLS.

PMID- 22474498
TI  - Inhibitory Effect of Ginsenoside Rg1 on Vascular Smooth Muscle Cell Proliferation
      Induced by PDGF-BB Is Involved in Nitric Oxide Formation.
AB  - Ginsenoside Rg1 (Rg1) has been reported to suppress the proliferation of vascular
      smooth muscle cells (VSMCs). This study aimed to observe the role of nitric oxide
      (NO) in Rg1-antiproliferative effect. VSMCs from the thoracic aorta of SD rats
      were cultured by tissue explant method, and the effect of Rg1 (20 mg.L(-1), 60
      mg.L(-1), and 180 mg.L(-1)) on platelet-derived growth factor-BB (PDGF-BB)
      induced proliferation was evaluated by MTT assay. The cell cycle was analyzed by
      flow cytometry. For probing the mechanisms, the content of NO in supernatant and
      cGMP level in VSMCs was measured by nitric oxide kit and cGMP radio-immunity kit,
      respectively; the expressions of protooncogene c-fos and endothelial NO synthase
      (eNOS) mRNA in the VSMCs were detected by real-time RT-PCR; the intracellular
      free calcium concentration ([Ca2(+)](i)) was detected with Fura-2/AM-loaded
      VSMCs. Comparing with that in normal group, Rg1 180 mg.L(-1) did not change the
      absorbance of MTT and cell percent of G(0)/G(1), G(2)/M, and S phase in normal
      cells (P > 0.05). Contrarily, PDGF-BB could increase the absorbance of MTT (P <
      0.01) and the percent of the S phase cells but decrease the G(0)/G(1) phase cell
      percent in the cell cycle, accompanied with an upregulating c-fos mRNA expression
      (P < 0.01), which was reversed by additions of Rg1(20 mg.L(-1), 60 mg.L(-1), and
      180 mg.L(-1)). Rg1 administration could also significantly increase the NO
      content in supernatant and the cGMP level in VSMCs, as well as the eNOS mRNA
      expression in the cells, in comparison of that in the group treated with PDGF-BB
      alone (P < 0.01). Furthermore, Rg1 caused a further increase in the elevated
      [Ca(2+)](i) induced by PDGF-BB. It was concluded that Rg1 could inhibit the VSMC
      proliferation induced by PDGF-BB through restricting the G(0)/G(1) phase to S
      phase progression in cell cycle. The mechanisms may be related to the
      upregulation of eNOS mRNA and the increase of the formation of NO and cGMP.

PMID- 22474499
TI  - Berberine improves insulin sensitivity by inhibiting fat store and adjusting
      adipokines profile in human preadipocytes and metabolic syndrome patients.
AB  - Berberine is known to inhibit the differentiation of 3T3-L1 cells in vitro,
      improve glycemic control, and attenuate dyslipidemia in clinical study. The aim
      of this study was to investigate the effects of berberine on preadipocytes
      isolated from human omental fat and in metabolic syndrome patients treated with
      berberine for 3 months. We have shown that treatment with 10 MUM berberine
      resulted in a major inhibition of human preadipocyte differentiation and leptin
      and adiponectin secretion accompanied by downregulation of PPARgamma2,
      C/EBPalpha, adiponectin, and leptin mRNA expression. After 3 months of treatment,
      metabolic syndrome patients showed decrease in their BMI (31.5 +/- 3.6 versus
      27.4 +/- 2.4 kg/m(2)) and leptin levels (8.01 versus 5.12 MUg/L), as well as
      leptin/adiponectin ratio and HOMA-IR. These results suggest that berberine
      improves insulin sensitivity by inhibiting fat store and adjusting adipokine
      profile in human preadipocytes and metabolic syndrome patients.

PMID- 22474500
TI  - Medical ethnobiology and ethnopharmacology in latin america.

PMID- 22474501
TI  - Efficacy of Bidens pilosa Extract against Herpes Simplex Virus Infection In Vitro
      and In Vivo.
AB  - The development of strains of herpes simplex virus (HSV) resistant to drugs has
      been reported among the immunocompromised patients. Thus, there is a need to
      develop new therapeutic agents for HSV infections. We evaluated the anti-HSV
      activity of Bidens pilosa (B. pilosa), a tropical weed, in tissue culture cells
      and a mouse model. B. pilosa extract showed potent virucidal activity. It
      inhibited plaque formation and suppressed virus yield in Vero and RAW 264.7 cells
      infected with HSV-1 and HSV-2. Both the binding of virus to host cells and
      penetration of virus into cells were also blocked by B. pilosa. Furthermore, B.
      pilosa was effective against thymidine kinase-deficient and phosphonoacetate
      resistant HSV-1 strains. B. pilosa treatment increased the survival rate of HSV
      infected mice and limited the development of skin lesions. Our results indicate
      that B. pilosa has anti-HSV activity and is thus a potentially useful medical
      plant for treatment of HSV infection.

PMID- 22474502
TI  - Antidiabetic Effect of an Active Components Group from Ilex kudingcha and Its
      Chemical Composition.
AB  - The leaves of Ilex kudingcha are used as an ethnomedicine in the treatment of
      symptoms related with diabetes mellitus and obesity throughout the centuries in
      China. The present study investigated the antidiabetic activities of an active
      components group (ACG) obtained from Ilex kudingcha in alloxan-induced type 2
      diabetic mice. ACG significantly reduced the elevated levels of serum glycaemic
      and lipids in type 2 diabetic mice. 3-Hydroxy-3-methylglutaryl coenzyme A
      reductase and glucokinase were upregulated significantly, while fatty acid
      synthetase, glucose-6-phosphatase catalytic enzyme was downregulated in diabetic
      mice after treatment of ACG. These findings clearly provided evidences regarding
      the antidiabetic potentials of ACG from Ilex kudingcha. Using LC-DAD/HR-ESI-TOF
      MS, six major components were identified in ACG. They are three dicaffeoylquinic
      acids that have been reported previously, and three new triterpenoid saponins,
      which were the first time to be identified in Ilex kudingcha. It is reasonable to
      assume that antidiabetic activity of Ilex kudingcha against hyperglycemia
      resulted from these six major components. Also, synergistic effects among their
      compounds may exist in the antidiabetic activity of Ilex kudingcha.

PMID- 22474504
TI  - The Movement Imagery Questionnaire-Revised, Second Edition (MIQ-RS) Is a Reliable
      and Valid Tool for Evaluating Motor Imagery in Stroke Populations.
AB  - Mental imagery can improve motor performance in stroke populations when combined
      with physical therapy. Valid and reliable instruments to evaluate the imagery
      ability of stroke survivors are needed to maximize the benefits of mental imagery
      therapy. The purposes of this study were to: examine and compare the test-retest
      intra-rate reliability of the Movement Imagery Questionnaire-Revised, Second
      Edition (MIQ-RS) in stroke survivors and able-bodied controls, examine internal
      consistency of the visual and kinesthetic items of the MIQ-RS, determine if the
      MIQ-RS includes both the visual and kinesthetic dimensions of mental imagery,
      correlate impairment and motor imagery scores, and investigate the criterion
      validity of the MIQ-RS in stroke survivors by comparing the results to the KVIQ
      10. Test-retest analysis indicated good levels of reliability (ICC range: .83
      .99) and internal consistency (Cronbach alpha: .95-.98) of the visual and
      kinesthetic subscales in both groups. The two-factor structure of the MIQ-RS was
      supported by factor analysis, with the visual and kinesthetic components
      accounting for 88.6% and 83.4% of the total variance in the able-bodied and
      stroke groups, respectively. The MIQ-RS is a valid and reliable instrument in the
      stroke population examined and able-bodied populations and therefore useful as an
      outcome measure for motor imagery ability.

PMID- 22474505
TI  - Neuroprotective Effects of San-Huang-Xie-Xin-Tang in the MPP(+)/MPTP Models of
      Parkinson's Disease In Vitro and In Vivo.
AB  - San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix,
      and Rhei rhizoma, is a traditional Chinese medicine used for complementary and
      alternative therapy of cardiovascular and neurodegenerative diseases via its anti
      inflammatory and antioxidative effects. The aim of this study is to investigate
      the protective effects of SHXT in the 1-methyl-4-phenylpyridinium (MPP(+))/1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson's disease.
      Rat primary mesencephalic neurons and mouse Parkinson disease model were used in
      this study. Oxidative stress was induced by MPP(+) in vitro and MPTP in vivo. In
      MPP(+)-treated mesencephalic neuron cultures, SHXT significantly increased the
      numbers of TH-positive neurons. SHXT reduced apoptotic signals (cytochrome and
      caspase) and apoptotic death. MPP(+)-induced gp91(phox) activation and ROS
      production were attenuated by SHXT. In addition, SHXT increased the levels of GSH
      and SOD in MPP(+)-treated neurons. In MPTP animal model, SHXT markedly increased
      TH-positive neurons in the substantia nigra pars compacta (SNpc) and improved
      motor activity of mice. In conclusion, the present results reveal the evidence
      that SHXT possesses beneficial protection against MPTP-induced neurotoxicity in
      this model of Parkinson's disease via its antioxidative and antiapoptotic
      effects. SHXT might be a potentially alternative and complementary medicine for
      neuroprotection.

PMID- 22474506
TI  - Validation Study of Kim's Sham Needle by Measuring Facial Temperature: An N-of-1
      Randomized Double-Blind Placebo-Controlled Clinical Trial.
AB  - Introduction. In 2008, Kim's sham needle was developed to improve the quality of
      double-blinded studies. The aim of this study is to validate Kim's sham needle by
      measuring facial temperature. Methods. We designed "N-of-1" trials involving 7
      smokers. One session was composed of 2 stimulations separated by a 2 h washout
      period. Six sessions were applied daily for all subjects. Infrared thermal
      imaging was used to examine the effects of acupuncture (HT8, KI2) on facial
      temperature following smoking-induced decrease. Results. All subjects
      demonstrated decreased temperatures after sham needle treatment, but 5 of the 7
      subjects showed increased temperatures after real needle treatment. 6 of the 7
      subjects showed a significant difference (P < 0.05) between treatments with real
      and sham needles. Thus, the physiological stimulation of Kim's sham needle is
      different from that of a real needle, suggesting that Kim's sham needle is a
      potential inactive control intervention.

PMID- 22474503
TI  - Neural acupuncture unit: a new concept for interpreting effects and mechanisms of
      acupuncture.
AB  - When an acupuncture needle is inserted into a designated point on the body and
      mechanical or electrical stimulation is delivered, various neural and neuroactive
      components are activated. The collection of the activated neural and neuroactive
      components distributed in the skin, muscle, and connective tissues surrounding
      the inserted needle is defined as a neural acupuncture unit (NAU). The
      traditionally defined acupoints represent an anatomical landmark system that
      indicates local sites where NAUs may contain relatively dense and concentrated
      neural and neuroactive components, upon which acupuncture stimulation would
      elicit a more efficient therapeutic response. The NAU-based local mechanisms of
      biochemical and biophysical reactions play an important role in acupuncture
      induced analgesia. Different properties of NAUs are associated with different
      components of needling sensation. There exist several central pathways to convey
      NAU-induced acupuncture signals, Electroacupuncture (EA) frequency-specific
      neurochemical effects are related to different peripheral and central pathways
      transmitting afferent signals from different frequency of NAU stimulation. More
      widespread and intense neuroimaging responses of brain regions to acupuncture may
      be a consequence of more efficient NAU stimulation modes. The introduction of the
      conception of NAU provides a new theoretical approach to interpreting effects and
      mechanisms of acupuncture in modern biomedical knowledge framework.

PMID- 22474507
TI  - The evaluation of chinese therapeutic food for the treatment of moderate
      dyslipidemia.
AB  - The clinical efficacy of the Chinese therapeutic food (specifically hawthorn
      fruit and Chinese kiwifruit-extract compound) on dyslipidemia was evaluated in
      this placebo-controlled, double blind, paired clinical trial conducted in
      Melbourne, Australia. Forty-three participants diagnosed with moderate
      dyslipidemia and met the study criteria were randomly assigned to Group A or B,
      with baseline characteristics matched. Twenty-seven participants completed all
      the tests, the blood lipid profile including total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and
      triglycerides (TG) was analysed. The traditional Chinese medicine diagnosis was
      made based on participants' symptoms and signs. The results indicate that a four
      week intake of the compound increased the serum HDL-c levels by 5% (P = 0.026)
      and decreased the ratios of TC/HDL-c and LDL-c/HDL-c (P = 0.012 and P = 0.044,
      resp.). The placebo intake did not significantly change the blood lipid profile.
      In the initial 43 participants with dyslipidemia, 76.7% of them were diagnosed
      with "Spleen deficiency" and 58.1% with "Liver qi stagnation." The intake of
      hawthorn fruit and Chinese kiwifruit extract compound may increase the serum
      levels of HDL-c and decrease the ratios of TC/HDL-c and LDL-c/HDL-c, therefore,
      may reduce the risk of cardiovascular disease.

PMID- 22474508
TI  - Botanical Extracts from Rosehip (Rosa canina), Willow Bark (Salix alba), and
      Nettle Leaf (Urtica dioica) Suppress IL-1beta-Induced NF-kappaB Activation in
      Canine Articular Chondrocytes.
AB  - The aim of this study was to characterize the anti-inflammatory mode of action of
      botanical extracts from rosehip (Rosa canina), willow bark (Salix alba), and
      nettle leaf (Urtica dioica) in an in vitro model of primary canine articular
      chondrocytes. Methods. The biological effects of the botanical extracts were
      studied in chondrocytes treated with IL-1beta for up to 72 h. Expression of
      collagen type II, cartilage-specific proteoglycan (CSPG), beta1-integrin, SOX-9,
      COX-2, and MMP-9 and MMP-13 was examined by western blotting. Results. The
      botanical extracts suppressed IL-1beta-induced NF-kappaB activation by inhibition
      of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation,
      and p65 nuclear translocation. These events correlated with downregulation of NF
      kappaB targets including COX-2 and MMPs. The extracts also reversed the IL-1beta
      induced downregulation of collagen type II, CSPG, beta1-integrin, and cartilage
      specific transcription factor SOX-9 protein expression. In high-density cultures
      botanical extracts stimulated new cartilage formation even in the presence of IL
      1beta. Conclusions. Botanical extracts exerted anti-inflammatory and anabolic
      effects on chondrocytes. The observed reduction of IL-1beta-induced NF-kappaB
      activation suggests that further studies are warranted to demonstrate the
      effectiveness of plant extracts in the treatment of OA and other conditions in
      which NF-kappaB plays pathophysiological roles.

PMID- 22474509
TI  - Kidney-tonifying recipe can repair alterations in adrenal medullary chromaffin
      cells in asthmatic rats.
AB  - Traditional Chinese medicine suggests that renal deficiency is a causative factor
      of asthma, and tonifying kidney drugs are believed to be an appropriate and
      beneficial treatment. The adrenal medullary chromaffin cells (AMCC) transition to
      the neuronal phenotype is known to occur in asthma, as evidenced by degranulation
      of chromaffin granules, decline of epinephrine (EPI) and phenylethanolamine-n
      methyl transferase (PNMT), and obvious alterations in cellular architecture. In
      this study, rats were sensitized and challenged with ovalbumin, then treated with
      Kidney-Tonifying Recipe (KTR) to evaluate the therapeutic effect. Tissues were
      evaluated for changes in pathology and EPI, PNMT, and peripherin expression.
      Degranulation of chromaffin granules and appearance of neurite-like process were
      found in AMCC from asthmatic rats, and these changes were corrected by KTR
      treatment. EPI and PNMT expressions were decreased in asthmatic rats and
      increased by KTR treatment. Peripherin expression was increased in asthmatic rats
      and decreased in the KTR-treated group. Morphological changes and decreases in
      EPI were observed when cultured AMCC were exposed to sera from asthmatic rats in
      vitro, and these changes were attenuated with the addition of sera from KRT
      treated rats. These results suggest that the Kidney-Tonifying Recipe is capable
      of repairing asthma-associated alterations in endocrine function and the
      ultrastructure of AMCC.

PMID- 22474510
TI  - Modified huo-luo-xiao-ling dan suppresses adjuvant arthritis by inhibiting
      chemokines and matrix-degrading enzymes.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the joints
      that can lead to deformities and disability. The prolonged use of conventionally
      used drugs is associated with severe adverse reactions. Therefore, safer and less
      expensive therapeutic products are continually being sought. Huo-Luo-Xiao-Ling
      dan (HLXL), a traditional Chinese herbal mixture, and its modified versions
      possess anti-arthritic activity. In this paper, we examined the influence of
      modified HLXL on two of the key mediators of arthritic inflammation and tissue
      damage, namely, chemokines and matrix-metalloproteinases (MMPs) in the rat
      adjuvant-induced arthritis (AA) model of RA. We treated arthritic Lewis rats with
      HLXL (2.3 g/kg) by daily gavage beginning at the onset of AA. The control rats
      received the vehicle. At the peak phase of AA, rats were sacrificed and their
      draining lymph node cells (LNC) and spleen adherent cells (SAC) were tested. The
      HLXL-treated rats showed a significant reduction in the levels of chemokines
      (RANTES, MCP-1, MIP-1alpha, and GRO/KC), MMPs (MMP 2 and 9), as well as cytokines
      (IL-6 and IL-17) that induce them, compared to the control vehicle-treated rats.
      Thus, HLXL controls arthritis in part by suppressing the mediators of immune
      pathology, and it might offer a promising alternative/adjunct treatment for RA.

PMID- 22474511
TI  - Antibacterial Activities of Selected Cameroonian Plants and Their Synergistic
      Effects with Antibiotics against Bacteria Expressing MDR Phenotypes.
AB  - The present work was designed to assess the antibacterial properties of the
      methanol extracts of some Cameroonian medicinal plants and the effect of their
      associations with currently used antibiotics on multidrug resistant (MDR) Gram
      negative bacteria overexpressing active efflux pumps. The antibacterial
      activities of twelve methanol extracts of medicinal plants were evaluated using
      broth microdilution. The results of this test showed that three extracts Garcinia
      lucida with the minimal inhibitory concentrations (MIC) varying from 128 to 512
      MUg/mL, Garcinia kola (MIC of 256 to 1024 MUg/mL), and Picralima nitida (MIC of
      128 to 1024 MUg/mL) were active on all the twenty-nine studied bacteria including
      MDR phenotypes. The association of phenylalanine arginine beta-naphthylamide
      (PAbetaN or efflux pumps inhibitor) to different extracts did not modify their
      activities. At the concentration of MIC/2 and MIC/5, the extracts of P. nitida
      and G. kola improved the antibacterial activities of some commonly used
      antibiotics suggesting their synergistic effects with the tested antibiotics. The
      results of this study suggest that the tested plant extracts and mostly those
      from P. nitida, G. lucida and G. kola could be used alone or in association with
      common antibiotics in the fight of bacterial infections involving MDR strains.

PMID- 22474513
TI  - A survey of complementary and alternative medicine use in cancer patients treated
      with radiotherapy in Thailand.
AB  - Introduction. Use of complementary and alternative medicine (CAM) in cancer
      patients is increasingly acceptable worldwide, but most of the studies were
      surveyed from developed countries. In this study, we evaluated the first and
      large cohort of cancer patients with CAM use in Thailand. Materials and Methods.
      A self-administered questionnaire was completed by 248 cancer patients attending
      outpatient radiotherapy unit at Ramathibodi Hospital. Results. The prevalence of
      CAM use was 60.9%. The most frequently used CAM were dietary/vitamin supplements
      (56.9%). Independent predictors of CAM use were high income (P < 0.001) and
      cancer type (P = 0.019). About half of the patients (51%) reported positive
      effects from CAM use. Nevertheless, 9.4% of the patient also reported side
      effects. The majority of patients (58.3%) did not disclose their use of CAM to
      their doctors because they felt that it was not necessary for doctors to know
      (65.9%). The average spending for CAM use was 200 USD/month (range, 10-1,000).
      Conclusion. Although the cost for CAM is relatively expensive, the prevalence of
      CAM use in cancer patients in Thailand is high particularly, in patients with
      higher income. Therefore, all clinical oncologists should be concerned about the
      use of CAM during evaluation of the cancer patients.

PMID- 22474512
TI  - Chloroform Fraction of Centratherum anthelminticum (L.) Seed Inhibits Tumor
      Necrosis Factor Alpha and Exhibits Pleotropic Bioactivities: Inhibitory Role in
      Human Tumor Cells.
AB  - We investigated the antioxidant potential, cytotoxic effect, and TNF-alpha
      inhibition activity with NF-kappaB activation response in a chloroform fraction
      of Centratherum anthelminticum seeds (CACF). The antioxidant property of CACF was
      evaluated with DPPH, ORAC, and FRAP assays, which demonstrated significant
      antioxidant activity. The cytotoxicity of CACF was tested using the MTT assay;
      CACF effective inhibitory concentrations (IC(50)) for A549, PC-3, MCF-7, and WRL
      68 cells were 31.42 +/- 5.4, 22.61 +/- 1.7, 8.1 +/- 0.9, and 54.93 +/- 8.3
      MUg/mL, respectively. CACF effectively and dose-dependently inhibited TNF-alpha
      release, in vitro and in vivo. CACF inhibited TNF-alpha secretion in stimulated
      RAW264.7 macrophage supernatants with an IC(50) of 0.012 MUg/mL, without
      affecting their viability; the highest dose tested reduced serum TNF-alpha by
      61%. Acute toxicity testing in rats revealed that CACF was non-toxic at all doses
      tested. Matching the cytotoxic activity towards a mechanistic approach, CACF dose
      dependently exhibited in vitro inhibitory effects against the activation of NF
      kappaB translocation in MCF-7 cells. Preliminary phytochemical screening with
      GC/MS analysis detected 22 compounds in CACF, of which morpholinoethyl
      isothiocyanate was the most abundant (29.04%). The study reveals the potential of
      CACF in the treatment of breast cancer and in oxidative stress conditions with
      associated inflammatory responses.

PMID- 22474514
TI  - Drug target prediction based on the herbs components: the study on the
      multitargets pharmacological mechanism of qishenkeli acting on the coronary heart
      disease.
AB  - In this paper, we present a case study of Qishenkeli (QSKL) to research TCM's
      underlying molecular mechanism, based on drug target prediction and analyses of
      TCM chemical components and following experimental validation. First, after
      determining the compositive compounds of QSKL, we use drugCIPHER-CS to predict
      their potential drug targets. These potential targets are significantly enriched
      with known cardiovascular disease-related drug targets. Then we find these
      potential drug targets are significantly enriched in the biological processes of
      neuroactive ligand-receptor interaction, aminoacyl-tRNA biosynthesis, calcium
      signaling pathway, glycine, serine and threonine metabolism, and renin
      angiotensin system (RAAS), and so on. Then, animal model of coronary heart
      disease (CHD) induced by left anterior descending coronary artery ligation is
      applied to validate predicted pathway. RAAS pathway is selected as an example,
      and the results show that QSKL has effect on both rennin and angiotensin II
      receptor (AT1R), which eventually down regulates the angiotensin II (AngII).
      Bioinformatics combing with experiment verification can provide a credible and
      objective method to understand the complicated multitargets mechanism for Chinese
      herbal formula.

PMID- 22474515
TI  - Fractionation of an Extract of Pluchea odorata Separates a Property Indicative
      for the Induction of Cell Plasticity from One That Inhibits a Neoplastic
      Phenotype.
AB  - Introduction. Several studies demonstrated that anti-inflammatory remedies
      exhibit excellent anti-neoplastic properties. An extract of Pluchea odorata
      (Asteraceae), which is used for wound healing and against inflammatory
      conditions, was fractionated and properties correlating to anti-neoplastic and
      wound healing effects were separated. Methods. Up to six fractionation steps
      using silica gel, Sephadex columns, and distinct solvent systems were used, and
      eluted fractions were analysed by thin layer chromatography, apoptosis, and
      proliferation assays. The expression of oncogenes and proteins regulating cell
      migration was investigated by immunoblotting after treating HL60 cells with the
      most active fractions. Results. Sequential fractionations enriched anti
      neoplastic activities which suppressed oncogene expression of JunB, c-Jun, c-Myc,
      and Stat3. Furthermore, a fraction (F4.6.3) inducing or keeping up expression of
      the mobility markers MYPT, ROCK1, and paxillin could be separated from another
      fraction (F4.3.7), which inhibited these markers. Conclusions. Wound healing
      builds up scar or specific tissue, and hence, compounds enhancing cell migration
      support this process. In contrast, successful anti-neoplastic therapy combats
      tumour progression, and thus, suppression of cell migration is mandatory.

PMID- 22474516
TI  - Chinese Herb Astragalus membranaceus Enhances Recovery of Hemorrhagic Stroke:
      Double-Blind, Placebo-Controlled, Randomized Study.
AB  - We tested the effect of Astragalus membranaceus (AM) on acute hemorrhagic stroke.
      Seventy-eight patients were randomly assigned to Group A (3 g of AM three
      times/day for 14 days); or Group B (3 g of placebo herb). A total of 68 patients
      (Group A 36, Group B 32) completed the trial. The increase of functional
      independence measure scale score between baseline and week 4 was 24.53 +/- 23.40,
      and between baseline and week 12 was 34.69 +/- 28.89, in the Group A was greater
      than 11.97 +/- 11.48 and 23.94 +/- 14.8 in the Group B (both P?0.05). The
      increase of Glasgow outcome scale score between baseline and week 12 was 0.75 +/-
      0.77 in the Group A was greater than 0.41 +/- 0.50 in the Group B (P < 0.05). The
      results are preliminary and need a larger study to assess the efficacy of AM
      after stroke.

PMID- 22474517
TI  - Acupuncture Use among American Adults: What Acupuncture Practitioners Can Learn
      from National Health Interview Survey 2007?
AB  - This paper examined the National Health Interview Survey (NHIS) 2007 and explored
      acupuncture users sociodemographics characteristics, reasons and the nature of
      acupuncture use, and the relationship of such use with conventional medical care.
      All individuals who completed adults core interviews (N = 23,393) were included.
      Three subsets of samples (nonuser, former user, and recent user) were used in the
      analysis performed in Stata. Our findings revealed that ever acupuncture user
      (including former and recent user) increased from 4.2% to 6.3% of the population,
      representing 8.19 million and 14.01 million users in 2002 and 2007, respectively.
      We expected this trend to continue. People not only used acupuncture as a
      complementary and alternative approach to conventional treatment for a specific
      health condition, but also used it as a preventive means to promote general
      health. Effectiveness and safety appeared not to be the main predictors of
      acupuncture use; rather, awareness, cost, and insurance coverage played a bigger
      role in decision making.

PMID- 22474518
TI  - Cardioprotective effect of the compound yangshen granule in rat models with acute
      myocardial infarction.
AB  - The protective effect of Compound Yangshen Granules was observed in myocardial
      infarction rat model. Rats were randomly divided into 6 groups: the model group,
      the control group (sham operated), the positive drug group, and small, medium,
      and large dosage of the Yangshen granule groups, respectively. The rats in the 3
      Yangshen granule groups were orally administrated with 0.7 g/kg, 1.4 g/kg, and
      2.8 g/kg for 7 consecutive days, whereas the rats of the positive drug group
      treated with 0.14 g/kg of Danshen Dropping Pills, and rats in the control and
      model groups orally administrated with saline. The rat model of acute myocardial
      infarction was established with ligation of coronary artery. Electrocardiograms
      at different time points, the blood rheology, myocardial enzymes, infarct size,
      and myocardial morphologic changes were measured. The results demonstrated that
      the granules could improve blood rheology, decrease st-segment of
      electrocardiograms and the activities of LDH and CK in serum, reduce myocardial
      infarction size, and alleviate myocardial histopathologic changes. In addition,
      the effect of the granules depended on the dose administrated orally. The results
      suggest that the Yangshen granules could produce cardioprotection effect and have
      potential benefits in the prevention of ischemic heart disease.

PMID- 22474519
TI  - Effect of GCSB-5, a Herbal Formulation, on Monosodium Iodoacetate-Induced
      Osteoarthritis in Rats.
AB  - Therapeutic effects of GCSB-5 on osteoarthritis were measured by the amount of
      glycosaminoglycan in rabbit articular cartilage explants in vitro, in
      experimental osteoarthritis induced by intra-articular injection of
      monoiodoacetate in rats in vivo. GCSB-5 was orally administered for 28 days. In
      vitro, GCSB-5 inhibited proteoglycan degradation. GCSB-5 significantly suppressed
      the histological changes in monoiodoacetate-induced osteoarthritis. Matrix
      metalloproteinase (MMP) activity, as well as, the levels of serum tumor necrosis
      factor-alpha, cyclooxygenase-2, inducible nitric oxide synthase protein, and mRNA
      expressions were attenuated by GCSB-5, whereas the level of interleukin-10 was
      potentiated. By GCSB-5, the level of nuclear factor-kappaB p65 protein expression
      was significantly attenuated but, on the other hand, the level of inhibitor of
      kappaB-alpha protein expression was increased. These results indicate that GCSB-5
      is a potential therapeutic agent for the protection of articular cartilage
      against progression of osteoarthritis through inhibition of MMPs activity,
      inflammatory mediators, and NF-kappaB activation.

PMID- 22474520
TI  - A six-month supplementation of mulberry, korean red ginseng, and banaba decreases
      biomarkers of systemic low-grade inflammation in subjects with impaired glucose
      tolerance and type 2 diabetes.
AB  - We sought the long-term efficacy of traditionally used antidiabetic herbs in
      controlling blood glucose homeostasis and low-grade inflammation. Ninety-four
      subjects with either impaired glucose tolerance or mild T2D were randomized
      either to treatment arm or placebo arm and received 1 : 1 : 1 mixture of ginseng
      roots, mulberry leaf water extract, and banaba leaf water extract (6 g/d) for 24
      weeks. Oral 75 g glucose tolerance test was performed to measure glucose and
      insulin responses. Blood biomarkers of low-grade inflammation were also
      determined. Results found no significant difference in glucose homeostasis
      control measure changes. However, plasma intracellular adhesion molecule-1 (ICAM
      1) concentration was decreased showing a significant between-treatment changes (P
      = 0.037). The concentrations of vascular cell adhesion molecule-1 (VCAM-1) (P =
      0.014) and ICAM-1 (P = 0.048) were decreased in the treatment group at week 24,
      and the oxidized low-density lipoprotein (ox-LDL) concentration was reduced at
      week 24 compared to the baseline value in the treatment group (P = 0.003). These
      results indicate a long-term supplementation of ginseng, mulberry leaf, and
      banaba leaf suppresses inflammatory responses in T2D.

PMID- 22474521
TI  - Acupuncture for the treatment of opiate addiction.
AB  - Acupuncture is an accepted treatment worldwide for various clinical conditions,
      and the effects of acupuncture on opiate addiction have been investigated in many
      clinical trials. The present review systematically analyzed data from randomized
      clinical trials published in Chinese and English since 1970. We found that the
      majority agreed on the efficacy of acupuncture as a strategy for the treatment of
      opiate addiction. However, some of the methods in several included trials have
      been criticized for their poor quality. This review summarizes the quality of the
      study design, the types of acupuncture applied, the commonly selected acupoints
      or sites of the body, the effectiveness of the treatment, and the possible
      mechanism underlying the effectiveness of acupuncture in these trials.

PMID- 22474522
TI  - Portulaca oleracea Ameliorates Diabetic Vascular Inflammation and Endothelial
      Dysfunction in db/db Mice.
AB  - Type 2 diabetes is associated with significantly accelerated rates of micro- and
      macrovascular complications such as diabetic vascular inflammation and
      endothelial dysfunction. In the present study, we investigated the protective
      effect of the aqueous extract of Portulaca oleracea L. (AP), an edible plant used
      as a folk medicine, on diabetic vascular complications. The db/db mice were
      treated with AP (300 mg/kg/day, p.o.) for 10 weeks, and AP treatment markedly
      lowered blood glucose, plasma triglyceride, plasma level of LDL-cholesterol, and
      systolic blood pressure in diabetic db/db mice. Furthermore, AP significantly
      increased plasma level of HDL-cholesterol and insulin level. The impairment of
      ACh- and SNP-induced vascular relaxation of aortic rings were ameliorated by AP
      treatment in diabetic db/db mice. This study also showed that overexpression of
      VCAM-1, ICAM-1, E-selectin, MMP-2, and ET-1 were observed in aortic tissues of
      untreated db/db mice, which were significantly suppressed by treatment with AP.
      We also found that the insulin immunoreactivity of the pancreatic islets
      remarkably increased in AP treated db/db mice compared with untreated db/db mice.
      Taken together, AP suppresses hyperglycemia and diabetic vascular inflammation,
      and prevents the development of diabetic endothelial dysfunction for the
      development of diabetes and its vascular complications.

PMID- 22474523
TI  - Effects of Extract from Solid-State Fermented Cordyceps sinensis on Type 2
      Diabetes Mellitus.
AB  - Diabetes mellitus is the most common chronic disease in the world, and a wide
      range of drugs, including Chinese herbs, have been evaluated for the treatment of
      associated metabolic disorders. This study investigated the potential
      hypoglycemic and renoprotective effects of an extract from the solid-state
      fermented mycelium of Cordyceps sinensis (CS). We employed the KK/HIJ diabetic
      mouse model, in which the mice were provided with a high-fat diet for 8 weeks to
      induce hyperglycemia, followed by the administration of CS or rosiglitazone for 4
      consecutive weeks. Several parameters were evaluated, including changes in body
      weight, plasma lipid profiles, oral glucose tolerance tests, insulin tolerance
      tests, and plasma insulin concentrations. Our results show that the CS extract
      significantly elevated HDL/LDL ratios at 4 weeks and decreased body weight gain
      at 8 weeks. Interestingly, CS treatment did not lead to obvious improvements in
      hyperglycemia or resistance to insulin, while in vitro MTT assays indicated that
      CS protects pancreatic beta cells against the toxic effects of STZ. CS also
      enhanced renal NKA activity and reduced the accumulation of mesangial matrix and
      collagen deposition. In conclusion, CS extract can potentially preserve beta-cell
      function and offer renoprotection, which may afford a promising therapy for DM.

PMID- 22474524
TI  - Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast
      Like Synoviocytes in Patients with Rheumatoid Arthritis.
AB  - Hyperplasia of synovial membrane in rheumatoid arthritis (RA) is a critical
      pathological foundation for inducing articular injury. The janus kinase and
      signal transducer and activator of transcription (Jak-STAT) pathway plays a
      critical role in synovial membrane proliferation induced by platelet-derived
      growth factor (PDGF). To explore the anti-cell proliferation mechanism of
      curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome,
      the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were
      observed in vitro. In this study, the fibroblast-like synoviocytes (FLS) in
      patients with RA were collected and cultured. The following parameters were
      measured: cell proliferation (WST-1 assay), cell cycles (fluorescence-activated
      cell sorting, FACS), STAT1 and STAT3 activities (electrophoretic mobility shift
      assay, EMSA), and the protein expressions of phosphorylated Jak2, STAT1, and
      STAT3 (Western blot). It was shown that curcumol could inhibit the RA-FLS
      proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in
      vitro. The transcription factors activities of STAT1 and STAT3 were obviously
      elevated after PDGF-BB stimulation (P < 0.05). Super-shift experiments identified
      the STAT1 or STAT3 proteins in the complex. Furthermore, the different
      concentration curcumol could downregulate the DNA binding activities of STAT1 and
      STAT3 (P < 0.05) and inhibit the phosphorylation of Jak2 while it had no effect
      on the protein expressions of STAT1 and STAT3. Positive correlations were found
      between changes of cell proliferation and DNA-binding activities of STAT1 and
      STAT3, respectively (P < 0.01). In conclusion, curcumol might suppress the FLS
      proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2
      phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which
      could provide theoretical foundation for clinical treatment of RA.

PMID- 22474525
TI  - Myricetin Increases Hepatic Peroxisome Proliferator-Activated Receptor alpha
      Protein Expression and Decreases Plasma Lipids and Adiposity in Rats.
AB  - The aim of this study was to investigate the antiobesity and antihyperlipidaemic
      effects of myricetin. Myricetin exhibited a significant concentration-dependent
      decrease in the intracellular accumulation of triglyceride in 3T3-L1 adipocytes.
      The high-fat diet (HFD)-fed rats were dosed orally with myricetin or fenofibrate,
      once daily for eight weeks. Myricetin (300 mg kg(-1) per day) displayed similar
      characteristics to fenofibrate (100 mg kg(-1) per day) in reducing lowered body
      weight (BW) gain, visceral fat-pad weights and plasma lipid levels of HFD-fed
      rats. Myricetin also reduced the hepatic triglyceride and cholesterol contents,
      as well as lowered hepatic lipid droplets accumulation and epididymal adipocyte
      size in HFD-fed rats. Myricetin and fenofibrate reversed the HFD-induced down
      regulation of the hepatic peroxisome proliferator activated receptor (PPAR)alpha.
      HFD-induced decreases of the hepatic protein level of acyl-CoA oxidase and
      cytochrome P450 isoform 4A1 were up-regulated by myricetin and fenofibrate. The
      elevated expressions of hepatic sterol regulatory element binding proteins
      (SREBPs) of HFD-fed rats were lowered by myricetin and fenofibrate. These results
      suggest that myricetin suppressed BW gain and body fat accumulation by increasing
      the fatty acid oxidation, which was likely mediated via up-regulation of
      PPARalpha and down-regulation of SREBP expressions in the liver of HFD-fed rats.

PMID- 22474526
TI  - Massage for children undergoing hematopoietic cell transplantation: a qualitative
      report.
AB  - Background. No in-depth qualitative research exists about the effects of
      therapeutic massage with children hospitalized to undergo hematopoietic cell
      transplantation (HCT). The objective of this study is to describe parent
      caregivers' experience of the effects of massage/acupressure for their children
      undergoing HCT. Methods. We conducted a qualitative analysis of open-ended
      interviews with 15 parents of children in the intervention arm of a
      massage/acupressure trial. Children received both practitioner and parent
      provided massage/acupressure. Results. Parents reported that their child
      experienced relief from pain and nausea, relaxation, and greater ease falling
      asleep. They also reported increased caregiver competence and closeness with
      their child as a result of learning and performing massage/acupressure. Parents
      supported a semistandardized massage protocol. Conclusion. Massage/acupressure
      may support symptom relief and promote relaxation and sleep among pediatric HCT
      patients if administered with attention to individual patients' needs and
      hospital routines and may relieve stress among parents, improve caregiver
      competence, and enhance the sense of connection between parent and child.

PMID- 22474527
TI  - History and mechanism for treatment of intracerebral hemorrhage with scalp
      acupuncture.
AB  - Intracerebral hemorrhage (ICH) is an important public health problem with high
      rates of mortality, morbidity, and disability, but no clinically proven treatment
      strategy is available to date. Scalp acupuncture (SA) refers to a therapy for
      treating diseases by needling and stimulating the specific areas of the scalp.
      The evidence from clinical studies suggested that SA therapy may produce
      significant benefits for patients with acute ICH. However, the therapeutic
      mechanisms are yet not well addressed. Therefore, in this paper, we provide a
      comprehensive overview on the history and mechanisms of SA therapy on acute ICH.
      Although SA has been practiced for thousands of years in China and could date
      back to 5 BC, SA therapy for acute ICH develops only in the recent 30 years. The
      possible mechanisms associated with the therapeutic effects of SA on ICH include
      the influence on hematoma, brain edema, and blood brain barrier, the products
      released from haematoma, the immune and inflammatory reaction, focal
      perihemorrhagic hypoperfusion and hemorheology, neuroelectrophysiology, and so
      on. At last, the existence of instant effect of SA on acute ICH and its possible
      mechanisms are presented.

PMID- 22474528
TI  - Meta-Analysis of Randomized Controlled Trials on the Efficacy of Di'ao Xinxuekang
      Capsule and Isosorbide Dinitrate in Treating Angina Pectoris.
AB  - Objective. Randomized controlled trials (RCTs) on di'ao xinxuekang capsule (XXK)
      in treating angina pectoris were published only in Chinese and have not been
      systematically reviewed particularly for comparing XXK with isosorbide dinitrate
      (ISDN). This study aims to provide a comprehensive PRISMA compliant and
      internationally accessible systematic review and meta-analysis to evaluate the
      efficacies of XXK and ISDN in treating angina pectoris. Methods. The RCTs
      published between 1989 and 2011 on XXK and ISDN in treating angina pectoris were
      selected according to specific criteria. Meta-analysis was performed to evaluate
      the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after
      treatment. Odds ratios (OR) were used to measure effect sizes. Subgroup analysis,
      sensitivity analysis, and metaregression were conducted to evaluate the
      robustness of the results. Results. Seven RCTs with 550 participants were
      eligible. Overall ORs for comparing XXK with ISDN were 4.11 (95% CI :  2.57,
      6.55) in SYMPTOMS and 2.37 (95% CI : 1.46, 3.84) in ECG. Subgroup analysis,
      sensitivity analysis, and metaregression found no significant dependence of
      overall ORs upon specific study characteristics. Conclusion. The meta-analysis of
      eligible but limited RCTs demonstrates that XXK seems to be more effective than
      ISDN in treating angina pectoris. Further RCTs of high quality are warranted to
      be conducted for update of the results of this meta-analysis.

PMID- 22474529
TI  - Sino-European transcontinental basic and clinical high-tech acupuncture studies
      part 2: acute stimulation effects on heart rate and its variability in patients
      with insomnia.
AB  - This second part of a series of Sino-European high-tech acupuncture studies
      describes the first clinical transcontinental teleacupuncture measurements in
      patients with insomnia. Heart rate (HR) and heart rate variability (HRV)
      measurements in 28 patients (mean age +/- SD: 41.9 +/- 14.6 years) were performed
      under standardized conditions in Harbin, China, and the data analysis was
      performed in Graz, Austria. Similar to the first part of the series, the
      electrocardiograms (ECGs) were recorded by an HRV Medilog AR12 system during
      acupuncture of the Shenmen point (HT7) on the left hand. HR decreased
      significantly (P < 0.001) during and after acupuncture stimulation of the HT7
      acupuncture point. Total HRV increased significantly (P < 0.05) immediately after
      acupuncture stimulation, but there was no long-lasting effect. The values of the
      low-frequency (LF) and high-frequency (HF) band increased significantly after the
      stimulation compared to baseline values; however, the LF/HF ratio showed no
      significant changes. Together with the results of previous studies, the present
      results can serve as a solid basis for further development of acupressure or
      acupuncture stimulation equipment for complementary use in treating insomnia.

PMID- 22474530
TI  - Comparison of a Chinese Herbal Medicine (CCH1) and Lactulose as First-Line
      Treatment of Constipation in Long-Term Care: A Randomized, Double-Blind, Double
      Dummy, and Placebo-Controlled Trial.
AB  - Many institutionalized patients and their healthcare providers are dissatisfied
      with current laxative therapy. This study compared therapeutic efficacy, safety,
      and laxative cost of an herbal formula (CCH1) and lactulose for long stay
      patients with constipation. In this double-blind, double-dummy, and placebo
      controlled trial, we randomized 93 residents with chronic constipation from two
      long-term care facilities in Taiwan to receive either CCH1 with lactulose placebo
      or CCH1 placebo with lactulose for 8 weeks, then followed up for 4 weeks without
      study medication. Both treatments were effective and well tolerated for patients,
      but CCH1 produced more spontaneous bowel movements, less rectal treatments, less
      amount of rescue laxative, and lower laxative cost than lactulose during
      treatment. No significant differences were found in stool consistency, stool
      amount, global assessment, and safety concerns. In conclusion, our results
      suggest that CCH1 may have better efficacy and could be used as an alternative
      option to lactulose in the treatment of constipation in long-term care.

PMID- 22474531
TI  - Paeonol Protects Memory after Ischemic Stroke via Inhibiting beta-Secretase and
      Apoptosis.
AB  - Poststroke dementia commonly occurs following stroke, with its pathogenesis
      related to beta-amyloid production and apoptosis. The present study evaluate the
      effects of paeonol, one of the phenolic phytochemicals isolated from the Chinese
      herb Paeonia suffruticosa Andrews (MC), on protection from memory loss after
      ischemic stroke in the subacute stage. Rats were subjected to transient middle
      cerebral artery occlusion (tMCAo) with 10 min of ischemia. The data revealed that
      paeonol recovered the step-through latency in the retrieval test seven days after
      tMCAo, but did not improve the neurological deficit induced by tMCAo. Levels of
      Amyloid precursor protein (APP)- and beta-site APP cleaving enzyme (BACE; beta
      secretase)-immunoreactive cells, and terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling (TUNEL)-positive cells decreased in the
      paeonol-administered group. Western blotting revealed decreased levels of Bax
      protein in mitochondria and apoptosis-inducing factor (AIF) in cytosol following
      paeonol treatment. In conclusion, we speculate that paeonol protected memory
      after ischemic stroke via reducing APP, BACE, and apoptosis. Supression the level
      of Bax and blocking the release of AIF into cytosol might participate in the anti
      apoptosis provided by paeonol.

PMID- 22474532
TI  - Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute
      Lung Injury Is Associated with Nrf2 Activation.
AB  - The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional
      eastern Asian medicinal remedy for the treatment of various respiratory diseases,
      but the efficacy and underlying mechanisms remain poorly characterized. Here, we
      explored a potential usage of FGS for the treatment of acute lung injury (ALI), a
      highly fatal inflammatory lung disease that urgently needs effective
      therapeutics, and investigated a mechanism for the anti-inflammatory activity of
      FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced
      neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter
      assays, semiquantitative RT-PCR, and Western blot analyses show that while not
      affecting NF-kappaB, FGS activated Nrf2 and expressed Nrf2-regulated genes
      including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of
      mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of
      proinflammatory cytokines in including TNF-alpha and IL-1beta in the inflamed
      lungs. These results suggest that FGS effectively suppresses neutrophilic lung
      inflammation, which can be associated with, at least in part, FGS-activating anti
      inflammatory factor Nrf2. Our results suggest that FGS can be developed as a
      therapeutic option for the treatment of ALI.

PMID- 22474533
TI  - Renal protective effect of xiao-chai-hu-tang on diabetic nephropathy of type 1
      diabetic mice.
AB  - Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese medicine formula consisting of
      seven medicinal plants, is used in the treatment of various diseases. We show
      here that XCHT could protect type-1 diabetic mice against diabetic nephropathy,
      using streptozotocin (STZ)-induced diabetic mice and high-glucose (HG)-exposed
      rat mesangial cell (RMC) as models. Following 4 weeks of oral administration with
      XCHT, renal functions and renal hypertrophy significantly improved in the STZ
      diabetic mice, while serum glucose was only moderately reduced compared to
      vehicle treatment. Treatment with XCHT in the STZ-diabetic mice and HG-exposed
      RMC resulted in a decrease in expression levels of TGF-beta1, fibronectin, and
      collagen IV, with concomitant increase in BMP-7 expression. Data from DPPH assay,
      DHE stain, and CM-H(2)DCFDA analysis indicated that XCHT could scavenge free
      radicals and inhibit high-glucose-induced ROS in RMCs. Taken together, these
      results suggest that treatment with XCHT can improve renal functions in STZ
      diabetic mice, an effect that is potentially mediated through decreasing
      oxidative stress and production of TGF-beta1, fibronectin, and collagen IV in the
      kidney during development of diabetic nephropathy. XCHT, therefore merits further
      investigation for application to improve renal functions in diabetic disorders.

PMID- 22474534
TI  - Randomized Comparison of the Therapeutic Effect of Acupuncture, Massage, and
      Tachibana-Style-Method on Stiff Shoulders by Measuring Muscle Firmness, VAS,
      Pulse, and Blood Pressure.
AB  - To compare the therapeutic efficacy of acupuncture, massage, and Tachibana
      Ryojutsu (one of Japanese traditional body balance therapy techniques (SEITAI)),
      on stiff shoulders, the subjects' muscle firmness, blood pressure, pulse, VAS,
      and body temperature were measured before and after the treatment. Forty-seven
      volunteer subjects gave written informed consent to participate in this study.
      The subjects were randomly divided into three groups to receive acupuncture,
      massage, or Tachibana-Ryojutsu. Each therapy lasted for 90 seconds. The
      acupuncture treatment was applied by a retaining-needle at GB-21, massage was
      conducted softly on the shoulders, and Tachibana-Ryojutsu treated only the
      muscles and joints from the legs to buttocks without touching the shoulders or
      backs. The study indicated that the muscle firmness and VAS of the Tachibana
      Ryojutsu group decreased significantly in comparison with the acupuncture and
      massage groups after treatment.

PMID- 22474535
TI  - An efficient time-varying filter for detrending and bandwidth limiting the heart
      rate variability tachogram without resampling: MATLAB open-source code and
      Internet web-based implementation.
AB  - The heart rate variability (HRV) signal derived from the ECG is a beat-to-beat
      record of RR intervals and is, as a time series, irregularly sampled. It is
      common engineering practice to resample this record, typically at 4 Hz, onto a
      regular time axis for analysis in advance of time domain filtering and spectral
      analysis based on the DFT. However, it is recognised that resampling introduces
      noise and frequency bias. The present work describes the implementation of a time
      varying filter using a smoothing priors approach based on a Gaussian process
      model, which does not require data to be regular in time. Its output is directly
      compatible with the Lomb-Scargle algorithm for power density estimation. A web
      based demonstration is available over the Internet for exemplar data. The MATLAB
      (MathWorks Inc.) code can be downloaded as open source.

PMID- 22474536
TI  - Bayesian assessment of newborn brain maturity from two-channel sleep
      electroencephalograms.
AB  - Newborn brain maturity can be assessed by expert analysis of maturity-related
      patterns recognizable in polysomnograms. Since 36 weeks most of these patterns
      become recognizable in EEG exclusively, particularly, in EEG recorded via the two
      central-temporal channels. The use of such EEG recordings enables experts to
      minimize the disturbance of sleep, preparation time as well as the movement
      artifacts. We assume that the brain maturity of newborns aged 36 weeks and older
      can be automatically assessed from the 2-channel sleep EEG as accurately as by
      expert analysis of the full polysomnographic information. We use Bayesian
      inference to test this assumption and assist experts to obtain the full
      probabilistic information on the EEG assessments. The Bayesian methodology is
      feasibly implemented with Monte Carlo integration over areas of high posterior
      probability density, however the existing techniques tend to provide biased
      assessments in the absence of prior information required to explore a model space
      in detail within a reasonable time. In this paper we aim to use the posterior
      information about EEG features to reduce possible bias in the assessments. The
      performance of the proposed method is tested on a set of EEG recordings.

PMID- 22474537
TI  - Membrane protein stability analyses by means of protein energy profiles in case
      of nephrogenic diabetes insipidus.
AB  - Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low
      incidences in an estimated one per 25,000-30,000 live births. This disease is
      characterized by polyuria and compensatory polydypsia. The diverse underlying
      causes of DI can be central defects, in which no functional arginine vasopressin
      (AVP) is released from the pituitary or can be a result of defects in the kidney
      (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to
      concentrate their urine despite the presence of AVP. This antidiuretic hormone
      regulates the process of water reabsorption from the prourine that is formed in
      the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP
      driven cascade, which leads to the insertion of aquaporin-2 water channels into
      the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to
      NDI. We investigated a structure model of V2R in its bound and unbound state
      regarding protein stability using a novel protein energy profile approach.
      Furthermore, these techniques were applied to the wild-type and selected
      mutations of aquaporin-2. We show that our results correspond well to
      experimental water ux analysis, which confirms the applicability of our
      theoretical approach to equivalent problems.

PMID- 22474538
TI  - Therapeutic vascular compliance change may cause significant variation in
      coronary perfusion: a numerical study.
AB  - In some pathological conditions like aortic stiffening and calcific aortic
      stenosis (CAS), the microstructure of the aortic root and the aortic valve
      leaflets are altered in response to stress resulting in changes in tissue
      thickness, stiffness, or both. This aortic stiffening and CAS are thought to
      affect coronary blood flow. The goal of the present paper was to include the flow
      in the coronary ostia in the previous fluid structure interaction model we have
      developed and to analyze the effect of diseased tissues (aortic root stiffening
      and CAS) on coronary perfusion. Results revealed a significant impact on the
      coronary perfusion due to a moderate increase in the aortic wall stiffness and
      CAS (increase of the aortic valve leaflets thickness). A marked drop of coronary
      peak velocity occurred when the values of leaflet thickness and aortic wall
      stiffness were above a certain threshold, corresponding to a threefold of their
      normal value. Consequently, mild and prophylactic treatments such as smoking
      cessation, exercise, or diet, which have been proven to increase the aortic
      compliance, may significantly improve the coronary perfusion.

PMID- 22474539
TI  - Comparison of the data classification approaches to diagnose spinal cord injury.
AB  - In our previous study, we have demonstrated that analyzing the skin impedances
      measured along the key points of the dermatomes might be a useful supplementary
      technique to enhance the diagnosis of spinal cord injury (SCI), especially for
      unconscious and noncooperative patients. Initially, in order to distinguish
      between the skin impedances of control group and patients, artificial neural
      networks (ANNs) were used as the main data classification approach. However, in
      the present study, we have proposed two more data classification approaches, that
      is, support vector machine (SVM) and hierarchical cluster tree analysis (HCTA),
      which improved the classification rate and also the overall performance. A
      comparison of the performance of these three methods in classifying traumatic SCI
      patients and controls was presented. The classification results indicated that
      dendrogram analysis based on HCTA algorithm and SVM achieved higher recognition
      accuracies compared to ANN. HCTA and SVM algorithms improved the classification
      rate and also the overall performance of SCI diagnosis.

PMID- 22474540
TI  - Risk-adjusted mortality: problems and possibilities.
AB  - The ratio of observed-to-expected deaths is considered a measure of hospital
      quality and for this reason will soon become a basis for payment. However, there
      are drivers of that metric more potent than quality: most important are medical
      documentation and patient acuity. If hositals underdocument and therefore do not
      capture the full "expected mortality" they may be tempted to lower their
      observed/expected ratio by reducing "observed mortality" through limiting access
      to the very ill. Underdocumentation occurs because hospitals do not recognize,
      and therefore cannot seek to confirm, specific comorbidities conferring high
      mortality risk. To help hospitals identify these comorbidities, this paper
      describes an easily implemented spread-sheet for evaluating comorbid conditions
      associated, in any particular hospital, with each discharge. This method
      identifies comorbidities that increase in frequency as mortality risk increases
      within each diagnostic grouping. The method is inductive and therefore
      independent of any particular risk-adjustment technique.

PMID- 22474541
TI  - Detecting epileptic seizure from scalp EEG using Lyapunov spectrum.
AB  - One of the inherent weaknesses of the EEG signal processing is noises and
      artifacts. To overcome it, some methods for prediction of epilepsy recently
      reported in the literature are based on the evaluation of chaotic behavior of
      intracranial electroencephalographic (EEG) recordings. These methods reduced
      noises, but they were hazardous to patients. In this study, we propose using
      Lyapunov spectrum to filter noise and detect epilepsy on scalp EEG signals only.
      We determined that the Lyapunov spectrum can be considered as the most expected
      method to evaluate chaotic behavior of scalp EEG recordings and to be robust
      within noises. Obtained results are compared to the independent component
      analysis (ICA) and largest Lyapunov exponent. The results of detecting epilepsy
      are compared to diagnosis from medical doctors in case of typical general
      epilepsy.

PMID- 22474542
TI  - Iterative methods for obtaining energy-minimizing parametric snakes with
      applications to medical imaging.
AB  - After a brief survey on the parametric deformable models, we develop an iterative
      method based on the finite difference schemes in order to obtain energy
      minimizing snakes. We estimate the approximation error, the residue, and the
      truncature error related to the corresponding algorithm, then we discuss its
      convergence, consistency, and stability. Some aspects regarding the prosthetic
      sugical methods that implement the above numerical methods are also pointed out.

PMID- 22474543
TI  - A Bayesian approach for decision making on the identification of genes with
      different expression levels: an application to Escherichia coli bacterium data.
AB  - A common interest in gene expression data analysis is to identify from a large
      pool of candidate genes the genes that present significant changes in expression
      levels between a treatment and a control biological condition. Usually, it is
      done using a statistic value and a cutoff value that are used to separate the
      genes differentially and nondifferentially expressed. In this paper, we propose a
      Bayesian approach to identify genes differentially expressed calculating
      sequentially credibility intervals from predictive densities which are
      constructed using the sampled mean treatment effect from all genes in study
      excluding the treatment effect of genes previously identified with statistical
      evidence for difference. We compare our Bayesian approach with the standard ones
      based on the use of the t-test and modified t-tests via a simulation study, using
      small sample sizes which are common in gene expression data analysis. Results
      obtained report evidence that the proposed approach performs better than standard
      ones, especially for cases with mean differences and increases in treatment
      variance in relation to control variance. We also apply the methodologies to a
      well-known publicly available data set on Escherichia coli bacterium.

PMID- 22474544
TI  - Preoperative evaluation of a surgical patient; preanesthetic interview by
      anesthesiology residents.

PMID- 22474545
TI  - Hypotensive bradycardic events during shoulder arthroscopic surgery under
      interscalene brachial plexus blocks.
AB  - Sudden, profound hypotensive and bradycardic events (HBEs) have been reported in
      more than 20% of patients undergoing shoulder arthroscopy in the sitting
      position. Although HBEs may be associated with the adverse effects of
      interscalene brachial plexus block (ISBPB) in the sitting position, the
      underlying mechanisms responsible for HBEs during the course of shoulder surgery
      are not well understood. The basic mechanisms of HBEs may be associated with the
      underlying mechanisms responsible for vasovagal syncope, carotid sinus
      hypersensitivity or orthostatic syncope. In this review, we discussed the
      possible mechanisms of HBEs during shoulder arthroscopic surgery, in the sitting
      position, under ISBPB. In particular, we focused on the relationship between HBEs
      and various types of syncopal reactions, the relationship between HBEs and the
      Bezold-Jarisch reflex, and the new contributing factors for the occurrence of
      HBEs, such as stellate ganglion block or the intraoperative administration of
      intravenous fentanyl.

PMID- 22474547
TI  - Effects of inspired oxygen fraction in discriminating venous from arterial blood
      in percutaneous central venous catheterization under general anesthesia.
AB  - BACKGROUND: A low fraction of inspired oxygen (FiO(2)) increases venous
      deoxygenated hemoglobin concentrations, making the color of the blood darker. The
      present study was aimed to determine the effects of FiO(2) on the ability to
      discriminate venous from arterial blood. METHODS: One-hundred and sixty surgical
      patients undergoing percutaneous central venous access of the internal jugular
      vein were randomly assigned to receive an FiO(2) of 0.2, 0.4, 0.6, or 1.0 (n = 40
      each) for at least 20 min prior to central line placement under general
      anesthesia. Vascular access was achieved with a 22-gauge needle; 2 ml of blood
      was withdrawn and shown to three physicians including the operator. Each of them
      was asked to identify the blood as 'arterial', 'venous' or 'not sure'.
      Simultaneous blood gas analysis of the samples was performed on blood taken from
      the puncture site and the artery after visual comparison to confirm blood's
      origin and hemodynamic measurements. RESULTS: Lowering FiO(2) progressively
      increased venous deoxygenated hemoglobin concentrations (2.24 +/- 1.12, 3.30 +/-
      1.08, 3.66 +/- 1.15, and 3.71 +/- 1.33 g/dl) in groups having an FiO(2) of 1.0,
      0.6, 0.4 and 0.2, respectively (P < 0.001), thereby facilitating the 'venous'
      blood identification (P < 0.001). Neither heart rate nor mean arterial pressure
      differed among the groups. None developed hypoxemia (percutaneous hemoglobin
      oxygen saturation < 90%) in any group during the study period. CONCLUSIONS: A low
      FiO(2) increases venous deoxygenated hemoglobin levels, thereby facilitating the
      recognition by clinicians of its venous origin in percutaneous central venous
      catheterization under general anesthesia.

PMID- 22474546
TI  - The preanesthetic interview by anesthesiology residents: analysis of time and
      content.
AB  - BACKGROUND: A preanesthetic visit can increase a patient's satisfaction. However,
      it is uncertain whether a preanesthetic visit by an anesthesiology resident can
      achieve the goal. We studied the time distribution for content of preanesthetic
      interviews (PI) and evaluated the patient's satisfaction with the PI. METHODS: We
      recorded the PI duration of 200 patients by a voice recorder. The degrees of
      patient satisfaction with the PI and the changes of anxiety level after the PI
      were quantified by a questionnaire. We analyzed the time distribution for content
      of the PI and the correlation between patient characteristics and PI duration or
      a patient's satisfaction. RESULTS: The total PI duration was 184 (134-286) sec
      (median, 25-75%), and the time distributions for content of the PI were 8 (5-10)
      of greeting, 45 (23-70) of history taking, 15 (10-20) of physical examination, 50
      (25-98) for obtainingan informed consent, 20 (10-30) of explanation for
      anesthetic planning, 15 (5-28) for explanation of patient controlled analgesia,
      and 10 (0-4) sec for questions and answers. Age, ASA physical status, and
      educational level were correlated with PI duration (P < 0.001). The patient's
      level of satisfaction was "very satisfied" in 39%, "satisfied" in 50%, and
      "moderate" in 11% of interviews. The anxiety level was "decreased" in 50%,
      "increased" in 8%, and "not changed" in 42% of patients. CONCLUSIONS: Although
      the duration of a PI given by residents was a relatively short, 89% of patients
      of were satisfied with the interview. The PI took a longer time to complete in
      patients of older age, higher ASA physical status, or lower educational levels.

PMID- 22474548
TI  - Effects of etomidate on bispectral index scale and spectral entropy during
      induction of anesthesia by means of the raw electroencephalographic and
      electromyographic characteristics.
AB  - BACKGROUND: Etomidate frequently induces myoclonus, so it may affect
      electromyographics (EMG). And EMG commonly has an effect on the bispectral index
      scale (BIS) and spectral entropy. This study was performed to compare the effect
      of etomidate on BIS, response entropy (RE) and state entropy (SE) during
      induction of anesthesia. METHODS: Fifty patients (ASA I or II) scheduled for
      elective surgery were included in this study. Anesthesia was induced with
      etomidate (0.3 mg/kg) and rocuronium (0.6 mg/kg). Patients also inhaled 4 vol%
      sevoflurane and 100% oxygen and, then intubated. BIS, RE, SE and Modified
      Observer's Assessment of Alertness/Sedation Scale (MOAA/S) were measured 4 times
      (before injection of etomidate [T0], at loss of eyelash reflex [T1], 90 seconds
      after rocuronium injection [T2], and after intubation [T3]). We also checked
      whether myoclonus occurred. RESULTS: Baseline values (T0) were 93.1 +/- 4.7 for
      BIS, 95.8 +/- 3.7 for RE and, 87.3 +/- 3.5 for SE. In comparison with T0, there
      were significantly differences in BIS (50.2 +/- 16.3), RE (76.8 +/- 18.5) and SE
      (66.3 +/- 17.4) at T1 (all P < 0.05). There were no significant differences at T2
      and T3. Thirty one patients had myoclonus. At the occurrence of myoclonus, RE and
      SE values significantly increased but not BIS (P < 0.05). CONCLUSIONS: In
      patients with myoclonus, at the loss of consciousness, spectral entropy did not
      decrease where as BIS did, suggesting that BIS may evaluate hypnotic levels
      better than spectral entropy during induction of anesthesia with etomidate.

PMID- 22474549
TI  - Spectral entropy for assessing the depth of propofol sedation.
AB  - BACKGROUND: For patients in the intensive care unit (ICU) or under monitored
      anesthetic care (MAC), the precise monitoring of sedation depth facilitates the
      optimization of dosage and prevents adverse complications from underor over
      sedation. For this purpose, conventional subjective sedation scales, such as the
      Observer's Assessment of Alertness/Sedation (OAA/S) or the Ramsay scale, have
      been widely utilized. Current procedures frequently disturb the patient's comfort
      and compromise the already well-established sedation. Therefore, reliable
      objective sedation scales that do not cause disturbances would be beneficial. We
      aimed to determine whether spectral entropy can be used as a sedation monitor as
      well as determine its ability to discriminate all levels of propofol-induced
      sedation during gradual increments of propofol dosage. METHODS: In 25 healthy
      volunteers undergoing general anesthesia, the values of response entropy (RE) and
      state entropy (SE) corresponding to each OAA/S (5 to 1) were determined. The
      scores were then analyzed during each 0.5 mcg/ml- incremental increase of a
      propofol dose. RESULTS: We observed a reduction of both RE and SE values that
      correlated with the OAA/S (correlation coefficient of 0.819 in RE-OAA/S and 0.753
      in SE-OAA/S). The RE and SE values corresponding to awake (OAA/S score 5), light
      sedation (OAA/S 3-4) and deep sedation (OAA/S 1-2) displayed differences (P <
      0.05). CONCLUSIONS: The results indicate that spectral entropy can be utilized as
      a reliable objective monitor to determine the depth of propofol-induced sedation.

PMID- 22474551
TI  - The effect of intravenous labetalol administration on hemodynamic responses
      during desflurane inhalation.
AB  - BACKGROUND: Inspired concentrations of desflurane >= 1 minimum alveolar
      anesthetic concentration (MAC) have been related to sympathetic stimulation such
      as hypertension and tachycardia. The current study examined whether labetalol, an
      alpha(1) and beta-adrenergic antagonist would blunt these hemodynamic responses.
      METHODS: Fifty-four ASA physical status I patients, aged 20-60 years, were
      enrolled in this study. The patients were randomly divided into 2 groups. The
      breathing circuit was primed with an end-tidal desflurane concentration of 1.2
      MAC in 6 L/min O(2). Normal saline 5 ml or labetalol 0.3 mg/kg was injected into
      groups S and L respectively. After 5 minutes, anesthesia was induced with
      intravenous etomidate 0.2 mg/kg and vecuronium 0.1 mg/kg. Each patient inhaled
      desflurane through a tight fitting facemask. Heart rate (HR), systolic blood
      pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and
      end-tidal concentration of desflurane (et-des) were measured at 5 minutes after
      saline or labetalol injection (baseline) and every 1 minute for 5 minutes after
      desflurane inhalation and for 2 minutes after intubation. RESULTS: In the saline
      injection group (group S), desflurane inhalation increased heart rate and blood
      pressure, while labetalol 0.3 mg/kg attenuated the heart rate and blood pressure
      increase in group L. After tracheal intubation, heart rate and blood pressure
      were significantly lower in group L than in group S. CONCLUSIONS: These results
      demonstrate that administration of intravenous labetalol is effective in
      attenuating tracheal intubation and desflurane-induced hemodynamic responses.

PMID- 22474550
TI  - Effect of ulinastatin on the rocuronium-induced neuromuscular blockade.
AB  - BACKGROUND: Ulinastatin is a glycoprotein derived from human urine and a serine
      protease inhibitor found in human urine and blood. Ulinastatin increases both
      liver blood flow and urine output. Rocuronium is eliminated mainly through the
      liver and partly through the kidney, hepatic elimination of rocuronium might be
      enhanced by ulinastatin. We examined the effect of ulinastatin on the
      neuromuscular block caused by rocuronium. METHODS: Forty four adult patients were
      randomly divided into two groups of 22 patients each, i.e. the study group and
      the control group. In the study group, a bolus dose of ulinastatin 5,000 U/kg was
      administered 2 min before the injection of rocuronium 0.6 mg/kg. In the control
      group, normal saline was administered instead of ulinastatin. For the monitoring
      of both onset and recovery from neuromuscular blockade, train-of-four (TOF) and
      post-tetanic count were used with TOF-Watch Sx. All patients underwent general
      anesthesia with total intravenous anesthesia (TIVA) of remifentanil and propofol,
      using the effect site target infusion system. RESULTS: In the study group, the
      onset of neuromuscular block was significantly slower than in the control group
      (P < 0.05). The recovery time from the rocuronium injection to the return of PTC
      was also significantly shorter in the study group than in the control group (P <
      0.05). Similarly, times to the return of T1, T2, T3, and T4 (i.e. the first,
      second, third, and fourth response of TOF) were significantly shorter in the
      study group than in the control group (P < 0.05). CONCLUSIONS: Ulinastatin
      significantly delays the onset of neuromuscular block and accelerates the
      recovery from the block caused by rocuronium.

PMID- 22474552
TI  - Incidence of intravascular insertion in thoracic epidural catheterization by
      using real time fluoroscopy.
AB  - BACKGROUND: Epidural analgesia is commonly used to provide several types of pain
      relief. Although this technique has been widely used with many advantages,
      currently the complications appear to be increasing. Especially, inadvertent
      intravascular cannulation and intravascular local anesthetic administration can
      lead to fatal consequences. METHODS: Data was collected on 296 patients
      undergoing elective thoracic or abdominal surgery. Two detection methods were
      utilized to confirm the epidural intravascular cannulation; flashback and
      aspiration of indwelling catheter, and injection of a contrast agent through the
      catheter under fluoroscopy were used to guide the placement of the catheter and
      to examine the intravascular cannulation. RESULTS: Epidural intravascular
      cannulation was reported in 4 out of 296 cases (1.4%), and 1 patient underwent
      subdural cannulation. Among the 4 cases of epidural intravascular cannulation,
      two were confirmed by the flashback and aspiration methods, while the remaining
      cases were only detected by real time fluoroscopy. CONCLUSIONS: In this study,
      inadvertent epidural intravascular cannulation occurred by as much as 1.4% of
      thoracic epidural catheterization. Utilizing real time fluoroscopy in addition to
      flashback and aspiration can enhance the sensitivity of detection.

PMID- 22474553
TI  - The effects of incremental continuous positive airway pressure on arterial
      oxygenation and pulmonary shunt during one-lung ventilation.
AB  - BACKGROUND: Although one lung ventilation (OLV) is frequently used for
      facilitating thoracic surgical procedures, arterial hypoxemia can occur while
      using one lung anesthesia. Continuous positive airway pressure (CPAP) in 5 or 10
      cmH(2)O to the non-ventilating lung is commonly recommended to prevent hypoxemia.
      We evaluated the effects of incremental CPAP to the non-ventilating lung on
      arterial oxygenation and pulmonary shunt without obstruction of the surgical
      field during OLV. METHODS: Twenty patients that were scheduled for one lung
      anesthesia were included in this study. Systemic and pulmonary hemodynamic data
      and blood gas analysis was recorded every fifteen minutes according to the
      patient's positions and CPAP levels. CPAP was applied from 0 cmH(2)O by 3 cmH(2)O
      increments until a surgeon notifies that the surgical field was obstructed by the
      expanded lung. Following that, pulmonary shunt fraction (Q(S)/Q(T)) was
      calculated. RESULTS: There were no significant differences of Q(S)/Q(T) between
      supine and lateral positions with two lung ventilation (TLV). OLV significantly
      decreased arterial oxygen partial pressure (PaO(2)) and increased Q(S)/Q(T)
      compared to TLV. PaO(2) and Q(S)/Q(T) significantly improved at 6 and 9 cmH(2)O
      of CPAP compared to 0 cmH(2)O. However, there were no significant differences of
      PaO(2) and Q(S)/Q(T) between 6 and 9 cmH(2)O CPAP. In 18 patients (90%), surgical
      fields were obstructed at 9 cmH(2)O CPAP. CONCLUSIONS: This study suggests that 6
      cmH(2)O CPAP effectively improved arterial oxygenation without interference of
      the surgical field during OLV when CPAP was applied from 0 cmH(2)O in 3 cmH(2)O
      increments.

PMID- 22474554
TI  - Efficacy of dexamethasone added to ramosetron for preventing postoperative nausea
      and vomiting in highly susceptible patients following spine surgery.
AB  - BACKGROUND: Opioid-based patient controlled analgesia (PCA) provides adequate
      pain control following spinal surgeries at the expense of increased risk of
      postoperative nausea and vomiting (PONV). We evaluated the efficacy of
      dexamethasone added to ramosetron, which is a newly developed five
      hydroxytryptamine receptor 3 antagonist with a higher receptor affinity and
      longer action duration compared to its congeners, on preventing PONV in highly
      susceptible patients receiving opioid-based IV PCA after spinal surgery. METHODS:
      One hundred nonsmoking female patients undergoing spinal surgery were randomly
      allocated to either a ramosetron group (group R) or a ramosetron plus
      dexamethasone group (group RD)., Normal saline (1 ml) or 5 mg of dexamethasone
      was injected before anesthetic induction, while at the end of the surgery,
      ramosetron (0.3 mg) was administered to all patients and fentanyl-based IV PCA
      was continued for 48 hrs. The incidence and severity of PONV, pain score and the
      amount of rescue antiemetics were assessed for 48 hours after surgery. RESULTS:
      The number of patients with moderate to severe nausea (20 vs. 10, P = 0.029), and
      overall incidence of vomiting (13 vs. 5, P = 0.037) were significantly lower in
      the group RD than in the group R, respectively. Rescue antiemetic was used less
      in the RD group without significance. CONCLUSIONS: Combination of ramosetron and
      dexamethasone significantly reduced the incidence of moderate to severe nausea
      and vomiting compared to ramosetron alone in highly susceptible patients
      receiving opioid-based IV PCA after surgery.

PMID- 22474555
TI  - Effects of clonidine on the activity of the rat glutamate transporter EAAT3
      expressed in Xenopus oocytes.
AB  - BACKGROUND: Clonidine has been shown to be a potent neuroprotectant by acting at
      alpha(2) receptors on glutamatergic neurons to inhibit the release of glutamate.
      The aim of this study is to investigate the effects of clonidine on the activity
      of EAAT3 that can regulate extracellular glutamate. METHODS: EAAT3 was expressed
      in the Xenopus oocytes. Using a two-electrode voltage clamp, membrane currents
      were recorded after application of 30 uM L-glutamate both in the presence and
      absence of various concentrations of clonidine. To determine the effects of
      clonidine on the K(m) and Vmax of EAAT3 and the reversibility of clonidine
      effects, membrane currents were recorded after the application of various
      concentrations of L-glutamate both in the presence and absence of 1.50 * 10(-7) M
      clonidine. RESULTS: Clonidine reduced the EAAT3 responses to L-glutamate in a
      concentration-dependent manner. This inhibition was statistically significant at
      higher concentrations than at the clinically relevant range. Clonidine at 1.50 *
      10(-7) M reduced the Vmax, but did not affect the K(m) of EAAT3 for L-glutamate.
      CONCLUSIONS: These results suggest that the direct inhibition of EAAT3 activity
      is not related to the sedation effect of clonidine and that the clonidine-induced
      reduction of EAAT3 activity provides additional data for the possible involvement
      of glutamatergic hyperactivity in the proconvulsant effect of clonidine.

PMID- 22474556
TI  - Fiberoptic intubation through a laryngeal mask airway as a management of
      difficult airwary due to the fusion of the entire cervical spine - A report of
      two cases -.
AB  - Patients with cervical spine instability and limited range of motion are
      challenge to anesthesiologists. It is important to consider alternatetive methods
      for securing the airway while maintaining neutral position and minimizing neck
      motion, because these patients are at increased risk for tracheal intubation
      failure and neurologic injury during airway management or position change. We
      experienced two cases that patients had cervical spine instability and severe
      limited range of motion due to the fusion of the entire cervical spine. One
      patient was a 6-year-old girl weighing 12.7 kg and had Klippel-Feil syndrome with
      Arnold-Chiari malformation, the other was a 24-year-old female weighing 31 kg and
      had juvenile rheumatoid arthritis. We successfully performed the intubation by
      using the fiberoptic intubation though a laryngeal mask airway in these two
      cases.

PMID- 22474557
TI  - Tracheal rupture after endotracheal intubation - A report of three cases -.
AB  - Tracheal rupture is a rare but serious complication that occurs after
      endotracheal intubation. It usually presents as a linear lesion in the membranous
      wall of the trachea, and is more prevalent in women and patients older than 50
      years. The clinical manifestations of tracheal injury include subcutaneous
      emphysema and respiratory distress. We report the cases of three female patients
      of old age presenting tracheal rupture after endotracheal intubation. Two cases
      received surgical repair without complication and one recovered uneventfully
      after conservative management. We presume that the tracheal injuries were caused
      by over-inflation of cuff and sudden movement of the tube by positional change.
      Therefore, we recommend cuff pressure monitoring during general anesthesia and
      minimized movement of the head and neck at positional change.

PMID- 22474558
TI  - Application of the continuous autotransfusion system (CATS) to prevent
      transfusion-related hyperkalemia following hyperkalemic cardiac arrest in an
      infant -A case report-.
AB  - Transfusion-induced hyperkalemia can lead to cardiac arrest, especially when the
      patient rapidly receives a large amount of red blood cells (RBCs), previously
      stored for a long period of time, irradiated or both. We report on a case of
      application of the Continuous AutoTransfusion System (CATS) to wash RBCs, in
      order to lower the high potassium (K(+)) level in the packed RBCs unit, during
      massive transfusion following transfusion-induced hyperkalemic cardiac arrest.
      After the washing process using CATS, there was no more electrocardiographic
      abnormality or cardiac arrest due to hyperkalemia. This case emphasizes the
      potential risk to develop transfusion-related hyperkalemic cardiac arrest, during
      massive transfusion of irradiated, pre-stored RBCs. CATS can be effectively used
      to lower the K(+) concentration in the packed RBCs unit, especially when the risk
      of transfusion-induced hyperkalemia is high.

PMID- 22474559
TI  - Severe airway obstruction in an infant with congenital tracheal stenosis and
      congenital heart disease -A case report-.
AB  - Congenital tracheal stenosis (CTS), though rare, is important because the
      mortality and morbidity rates are high in infants. Especially, associated
      congenital heart disease (CHD) in these infants may compound the effects of
      airway pathology. A 3-week-old patient with long-segmental tracheal stenosis
      below an anomalous right-upper lobe (RUL) bronchus had undergone a total
      correction of double outlet right ventricle. On third postoperative day,
      hypercarbia developed, and severe airway obstruction and atelectasis were
      detected. An emergency slide tracheoplasty was performed under cardiopulmonary
      bypass (CPB). The patient recovered well after the surgery. Thus, special
      attention needs to be paid during the postoperative intensive care of patients
      with congenital tracheal anomalies. Early detection and prompt diagnosis of
      airway obstruction can help reduce the morbidity and mortality rates. Further, it
      is important to select the suitable treatment of CTS associated with CHD.

PMID- 22474560
TI  - Hypertensive crisis during wide excision of gastrointestinal stromal cell tumor
      (GIST): Undiagnosed paraganglioma -A case report-.
AB  - Although paraganglioma (PGL), an extra-adrenal retroperitoneal pheochromocytoma
      (PHEO), is a rare catecholamine-secreting neuroendocrine tumor, it can cause
      severe hypertensive crisis during anesthesia or surgery if undiagnosed
      preoperatively. Extraluminal perigastric masses may be presumed to be
      gastrointestinal stromal tumors (GISTs) or soft tissue sarcomas even when
      histologic confirmation is not possible. Therefore, without a histologic
      diagnosis or symptoms of excessive catecholamine secretion, PGL may be mistaken
      for GIST. We report a case of preoperatively undiagnosed PGL which caused
      hypertensive crisis during anesthesia for retroperitoneal mass excision.

PMID- 22474561
TI  - Paradoxical air embolism due to electrosurgical vaporization during hysteroscopic
      myomectomy.

PMID- 22474562
TI  - Acute orbital myositis before Herpes zoster ophthalmicus.

PMID- 22474563
TI  - Iowa satisfaction with anesthesia scale.

PMID- 22474564
TI  - Intraoperative, rapid administration of high-dose fentanyl by a dysfunctioning
      plunger lock of a syringe pump; the siphon effect.

PMID- 22474565
TI  - Ochratoxigenic black species of Aspergilli in grape fruits of northern Italy
      identified by an improved PCR-RFLP procedure.
AB  - A collection of 356 isolates of Aspergillus spp. collected during 2006 and 2007
      from grapevines in northern Italy were identified through Internal Transcribed
      Spacer based Restriction Fragment Length Polymorphism (ITS-RFLP) and tested for
      ochratoxin A (OTA) production. Restriction endonuclease digestion of the ITS
      products using the endonucleases HhaI, HinfI and RsaI, distinguished five
      different RFLPs. From each pattern, three samples were sequenced and the
      nucleotide sequences showed different species corresponding to Aspergillus niger,
      A. carbonarius, A. tubingensis, A. japonicus and A. aculeatus. By comparing the
      sequences of the ITS regions, also the uniseriate species A. japonicus and A.
      aculeatus could be differentiated by HinfI digestion of the ITS products. Among
      the aspergilli, A. niger was the major species associated with grapes during 2006
      (57.4%), while A. carbonarius was the major species during 2007 (46.6%). All the
      strains of Aspergillus were tested for their ability to produce OTA on Yeast
      extract sucrose medium (YES), as it was tested as an optimal substrate for the
      evaluation of OTA production by black aspergilli. Out of 356 isolates, 63 (17.7%)
      isolates produced OTA ranging from 0.05 to 3.0 ug mL(-1). Most of the
      ochratoxigenic isolates were A. carbonarius (46) in both years, but also some
      strains of A. tubingensis (11) and A. japonicus (6) produced lower amounts of
      OTA.

PMID- 22474566
TI  - Plant ureases and related peptides: understanding their entomotoxic properties.
AB  - Recently, ureases were included in the arsenal of plant defense proteins,
      alongside many other proteins with biotechnological potential such as
      insecticides. Isoforms of Canavalia ensiformis urease (canatoxin-CNTX and jack
      bean urease-JBURE-I) are toxic to insects of different orders. This toxicity is
      due in part to the release of a 10 kDa peptide from the native protein, by
      cathepsin-like enzymes present in the insect digestive tract. The entomotoxic
      peptide, Jaburetox-2Ec, exhibits potent insecticidal activity against several
      insects, including many resistant to the native ureases. JBURE-I and Jaburetox
      2Ec cause major alterations of post-feeding physiological processes in insects,
      which contribute to, or can be the cause of, their entomotoxic effect. An
      overview of the current knowledge on plant urease processing and mechanisms of
      action in insects is presented in this review.

PMID- 22474567
TI  - Biocontrol of Penicillium nordicum growth and ochratoxin A production by native
      yeasts of dry cured ham.
AB  - Twelve yeast strains isolated from the surface of Italian typical dry-cured hams,
      belonging to D. hansenii, D. maramus, C. famata, C. zeylanoides and H. burtonii
      species, and previously selected for their ability to grow in dry-cured ham-like
      substrates, were screened for antagonistic activity against a toxigenic strain of
      P. nordicum and inhibition of ochratoxin A (OTA) biosynthesis. On average, yeast
      inhibitory activity was lowered by increasing fungal inoculum and enhanced by
      NaCl presence. In the assay conditions, H. burtonii and C. zeylanoides were the
      most effective, both in inhibiting P. nordicum growth and OTA production. D.
      hansenii was the species with the lowest inhibitory activity, especially in the
      absence of salt. OTA production dropped from the range < LOD - 5000 ppb in P.
      nordicum control plates to the range < LOD - 200 ppb in yeast-added plates. OTA
      production increased in the presence of NaCl in P. nordicum control plates, while
      salt enhanced inhibition against OTA production in yeast-added plates.

PMID- 22474568
TI  - Cytoskeleton as an emerging target of anthrax toxins.
AB  - Bacillus anthracis, the agent of anthrax, has gained virulence through its
      exotoxins produced by vegetative bacilli and is composed of three components
      forming lethal toxin (LT) and edema toxin (ET). So far, little is known about the
      effects of these toxins on the eukaryotic cytoskeleton. Here, we provide an
      overview on the general effects of toxin upon the cytoskeleton architecture.
      Thus, we shall discuss how anthrax toxins interact with their receptors and may
      disrupt the interface between extracellular matrix and the cytoskeleton. We then
      analyze what toxin molecular effects on cytoskeleton have been described, before
      discussing how the cytoskeleton may help the pathogen to corrupt general cell
      processes such as phagocytosis or vascular integrity.

PMID- 22474569
TI  - Sorption of ochratoxin A from aqueous solutions using beta-cyclodextrin
      polyurethane polymer.
AB  - The ability of a cyclodextrin-polyurethane polymer to remove ochratoxin A from
      aqueous solutions was examined by batch rebinding assays. The results from the
      aqueous binding studies were fit to two parameter models to gain insight into the
      interaction of ochratoxin A with the nanosponge material. The ochratoxin A
      sorption data fit well to the heterogeneous Freundlich isotherm model. The
      polymer was less effective at binding ochratoxin A in high pH buffer (9.5) under
      conditions where ochratoxin A exists predominantly in the dianionic state. Batch
      rebinding assays in red wine indicate the polymer is able to remove significant
      levels of ochratoxin A from spiked solutions between 1-10 MUg.L(-1). These
      results suggest cyclodextrin nanosponge materials are suitable to reduce levels
      of ochratoxin A from spiked aqueous solutions and red wine samples.

PMID- 22474570
TI  - Developing a comparative docking protocol for the prediction of peptide
      selectivity profiles: investigation of potassium channel toxins.
AB  - During the development of selective peptides against highly homologous targets, a
      reliable tool is sought that can predict information on both mechanisms of
      binding and relative affinities. These tools must first be tested on known
      profiles before application on novel therapeutic candidates. We therefore present
      a comparative docking protocol in HADDOCK using critical motifs, and use it to
      "predict" the various selectivity profiles of several major alphaKTX scorpion
      toxin families versus K(v)1.1, K(v)1.2 and K(v)1.3. By correlating results across
      toxins of similar profiles, a comprehensive set of functional residues can be
      identified. Reasonable models of channel-toxin interactions can be then drawn
      that are consistent with known affinity and mutagenesis. Without biological
      information on the interaction, HADDOCK reproduces mechanisms underlying the
      universal binding of alphaKTX-2 toxins, and K(v)1.3 selectivity of alphaKTX-3
      toxins. The addition of constraints encouraging the critical lysine insertion
      confirms these findings, and gives analogous explanations for other families,
      including models of partial pore-block in alphaKTX-6. While qualitatively
      informative, the HADDOCK scoring function is not yet sufficient for accurate
      affinity-ranking. False minima in low-affinity complexes often resemble true
      binding in high-affinity complexes, despite steric/conformational penalties
      apparent from visual inspection. This contamination significantly complicates
      energetic analysis, although it is usually possible to obtain correct ranking via
      careful interpretation of binding-well characteristics and elimination of false
      positives. Aside from adaptations to the broader potassium channel family, we
      suggest that this strategy of comparative docking can be extended to other
      channels of interest with known structure, especially in cases where a critical
      motif exists to improve docking effectiveness.

PMID- 22474572
TI  - Using chemical approaches to understand RNA structure and function in biology.

PMID- 22474571
TI  - Host-defense activities of cyclotides.
AB  - Cyclotides are plant mini-proteins whose natural function is thought to be to
      protect plants from pest or pathogens, particularly insect pests. They are
      approximately 30 amino acids in size and are characterized by a cyclic peptide
      backbone and a cystine knot arrangement of three conserved disulfide bonds. This
      article provides an overview of the reported pesticidal or toxic activities of
      cyclotides, discusses a possible common mechanism of action involving disruption
      of biological membranes in pest species, and describes methods that can be used
      to produce cyclotides for potential applications as novel pesticidal agents.

PMID- 22474574
TI  - The autoimmune tautology: an in silico approach.
AB  - There is genetic evidence of similarities and differences among autoimmune
      diseases (AIDs) that warrants looking at a general panorama of what has been
      published. Thus, our aim was to determine the main shared genes and to what
      extent they contribute to building clusters of AIDs. We combined a text-mining
      approach to build clusters of genetic concept profiles (GCPs) from the literature
      in MedLine with knowledge of protein-protein interactions to confirm if genes in
      GCP encode proteins that truly interact. We found three clusters in which the
      genes with the highest contribution encoded proteins that showed strong and
      specific interactions. After projecting the AIDs on a plane, two clusters could
      be discerned: Sjogren's syndrome-systemic lupus erythematosus, and autoimmune
      thyroid disease-type1 diabetes-rheumatoid arthritis. Our results support the
      common origin of AIDs and the role of genes involved in apoptosis such as CTLA4,
      FASLG, and IL10.

PMID- 22474573
TI  - Neurological Disorders in Primary Sjogren's Syndrome.
AB  - Sjogren's syndrome is an autoimmune disease characterized by an autoimmune
      exocrinopathy involving mainly salivary and lacrimal glands. The
      histopathological hallmark is periductal lymphocytic infiltration of the exocrine
      glands, resulting in loss of their secretory function. Several systemic
      manifestations may be found in patients with Sjogren's syndrome including
      neurological disorders. Neurological involvement ranges from 0 to 70% among
      various series and may present with central nervous system and/or peripheral
      nervous system involvement. This paper endeavors to review the main clinical
      neurological manifestations in Sjogren syndrome, the physiopathology, and their
      therapeutic response.

PMID- 22474575
TI  - Transient Silencing of a Type IV P-Type ATPase, Atp10c, Results in Decreased
      Glucose Uptake in C2C12 Myotubes.
AB  - Atp10c is a strong candidate gene for diet-induced obesity and type 2 diabetes.
      To identify molecular and cellular targets of ATP10C, Atp10c expression was
      altered in vitro in C2C12 skeletal muscle myotubes by transient transfection with
      an Atp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation
      caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected
      cells coupled with a significant upregulation of native mitogen-activated protein
      kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was
      significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression
      were observed. The involvement of MAPKs was confirmed using the specific
      inhibitor SB203580, which downregulated the expression of native and
      phosphorylated MAPK proteins in transfected cells without any changes in insulin
      stimulated glucose uptake. Results indicate that Atp10c regulates glucose
      metabolism, at least in part via the MAPK pathway, and, thus, plays a significant
      role in the development of insulin resistance and type 2 diabetes.

PMID- 22474576
TI  - Relation of growth rate from birth to three months and four to six months to body
      mass index at ages four to six years.
AB  - Background. While rapid early weight gain are common in children who become obese
      later in life, so is growth faltering in the first 3 months of life. Objective.
      We seek to determine what relationship weight gain in the first six months of
      age, separated into two 3-month periods, have with the BMI of children ages 4 to
      6 years in an inner-city community. Subjects. A convenience sample cohort of 154
      children attending an inner-city clinic. Methods. Consecutive charts were
      reviewed retrospectively. Age, gender, birth weight and weight change in the
      first and second 3 months of life were introduced as fixed factors using mixed
      linear models with BMI in years 4 to 6 as the dependent variable. Results. Weight
      change quartile in the first 3 months of life did not predict of BMI in years 4
      to 6; however, weight changes quartiles during months 4 to 6 were significant
      predictors for subsequent overweight. Conclusion. The data presented herein
      suggest that, for this specific population, weight gain can be promoted when it
      is most essential. It is necessary, however, to identify intermediary variables
      that could affect outcomes in this and other communities.

PMID- 22474577
TI  - The acute impact of ingestion of sourdough and whole-grain breads on blood
      glucose, insulin, and incretins in overweight and obese men.
AB  - Consumption of whole-grain and sourdough breads is associated with improved
      glucose homeostasis. We examined the impact of commercial breads on biomarkers of
      glucose homeostasis in subjects at risk for glucose intolerance. In a randomized,
      crossover study, overweight or obese males ingested 11-grain, sprouted-grain, 12
      grain, sourdough, or white bread on different occasions, matched for available
      carbohydrate (50 g) in part 1 (n = 12) and bread mass (107 g) in part 2 (n = 11),
      and blood glucose, insulin and glucose-dependent insulinotropic polypeptide (GIP)
      and glucagon-like peptide-1 (GLP-1) were determined for 3 h. In part 1, glucose
      response for sprouted-grain was lower than 11-grain, sourdough, and white breads.
      Insulin area under the curve (AUC) for sourdough and white was lower than 11
      grain and sprouted-grain breads. GLP-1 response to sourdough was lower than all
      breads. In part 2, glucose and insulin AUC for sourdough was greater than 11
      grain, sprouted-grain, and 12-grain breads. Sprouted-grain bread improved
      glycemia by lowering glucose response and increasing GLP-1 response. In
      overweight and obese men, the glycemic response to sprouted grain bread was
      reduced in both parts 1 and 2 while the other whole-grain test breads did not
      improve metabolic responses in the acute postprandial state.

PMID- 22474578
TI  - Changes in serum lipids and blood glucose in non diabetic patients with metabolic
      syndrome after mixed meals of different composition.
AB  - Aims. To investigate the postprandial changes in serum lipoproteins and blood
      glucose and to verify whether different nutrient composition of the meal elicits
      different response in patients with (MetS+) and without (MetS-) metabolic
      syndrome. Research Design and Methods. 50 MetS+ patients and 50 age- and sex
      matched MetS- consumed a regular lunch chosen among those more similar to their
      usual diet. Blood was drawn in the morning after 12-hour fasting and 2 and 4:30
      hours after the meal. Results. Serum triglycerides increased more in MetS+ (35%,
      4:30 hours after the meal) than in MetS- (29%), HDL-cholesterol decreased 2 hours
      after the meal in both groups (-4% and -5%, resp.). Blood sugar similarly
      increased in both groups (19%, 2 hours after the meal in MetS+ and 17% in MetS-)
      and plasma insulin increased more and remained high longer in MetS+ (73.5 and
      52.3 MUU/mL, 2 and 4:30 hours after the meal) than in MetS- (46.7 and 21.6
      MUU/mL). Difference in nutrient composition of the meal (carbohydrate 57%, fat
      28% versus carbohydrate 45%, fat 35%) was not associated with differences in
      postprandial levels of triglycerides, HDL-cholesterol, glucose, and insulin
      within each group. Conclusions. As compared with MetS-, MetS+ patients show a
      greater hypertriglyceridemic and hyperinsulinemic response to a regular lunch
      whatever the carbohydrate or fat content of the meal.

PMID- 22474579
TI  - Inflammatory and oxidative stress responses to high-carbohydrate and high-fat
      meals in healthy humans.
AB  - The postprandial state is hypothesised to be proinflammatory and prooxidative,
      but the relative contributions of fat versus carbohydrate are unclear. Therefore,
      we examined inflammation and oxidative stress responses in serum and skeletal
      muscle before and after 1000 kcal meals, which were high in either fat or
      carbohydrate in 15 healthy individuals. Serum and muscle expression of IL6 was
      elevated 3 hours after each meal, independently of macronutrient composition (P <
      0.01). Serum IL18 was decreased after high-fat meal only (P < 0.01). Plasma total
      antioxidative status and muscle Cu/Zn-superoxide dismutase were decreased after
      high-carbohydrate meal only (P < 0.05). We conclude that a high-carbohydrate meal
      may evoke a greater postprandial oxidative stress response, whereas both fat and
      carbohydrate increased IL6. We speculate that the observed increases in
      postprandial IL6, without increases in any other markers of inflammation, may
      indicate a normal IL6 response to enhance glucose uptake, similar to its role
      postexercise.

PMID- 22474581
TI  - Adolescents' perceptions of their consent to psychiatric mental health treatment.
AB  - The purpose of this paper is to present the findings of a small-scale study in
      which the decision-making process of adolescents who consent to psychiatric
      mental health treatment was examined. Sixteen (16) adolescents were interviewed
      about their decisions related to initial and continued treatment, along with
      their understanding of minor consent laws. Interviews were audio-recorded, and
      transcripts were analyzed through concept analysis. Findings are presented in the
      context of the decision-making steps and research questions. Most adolescents did
      not recognize consequences related to psychiatric mental health treatment and did
      not assimilate and integrate information provided to them about treatment
      choices. Adolescents disagreed with current minor consent laws that allow minors
      to consent to certain healthcare treatments without the required consent of the
      parent. Further, adolescents reported that a collaborative approach in making
      decisions about the adolescent's psychiatric mental health treatment was most
      facilitative of achieving the goals of treatment.

PMID- 22474582
TI  - Physician Wages in States with Expanded APRN Scope of Practice.
AB  - In recent years, states have looked to reforms in advanced practice nursing scope
      of practice (SOP) barriers as a potential means to increase access to primary
      care while reducing costs. Currently, 16 states and the District of Columbia
      permit advanced practice registered nurses to practice independently of
      physicians, allowing them to perform functions such as diagnosing and prescribing
      under their own authority within the primary care setting. Given the resistance
      of many physician associations to these reforms, we asked whether the economic
      interests of primary care physicians might be affected by reforms. Using the
      Bureau of Labor Statistics data on earnings, we compared primary care physicians'
      earnings in states that have instituted SOP reforms to those that maintain these
      practice barriers. We also compared surgeons' earnings as a control group.
      Lastly, we compared the rate of growth in the earnings of primary care physicians
      and surgeons over the last ten years. This preliminary analysis revealed no
      evidence of differences in earnings across the two groups of states.

PMID- 22474580
TI  - Resistance Training in Type II Diabetes Mellitus: Impact on Areas of Metabolic
      Dysfunction in Skeletal Muscle and Potential Impact on Bone.
AB  - The prevalence of Type II Diabetes mellitus (T2DM) is increasing rapidly and will
      continue to be a major healthcare expenditure burden. As such, identification of
      effective lifestyle treatments is paramount. Skeletal muscle and bone display
      metabolic and functional disruption in T2DM. Skeletal muscle in T2DM is
      characterized by insulin resistance, impaired glycogen synthesis, impairments in
      mitochondria, and lipid accumulation. Bone quality in T2DM is decreased,
      potentially due to the effects of advanced glycation endproducts on collagen,
      impaired osteoblast activity, and lipid accumulation. Although exercise is widely
      recognized as an important component of treatment for T2DM, the focus has largely
      been on aerobic exercise. Emerging research suggests that resistance training
      (strength training) may impose potent and unique benefits in T2DM. The purpose of
      this review is to examine the role of resistance training in treating the
      dysfunction in skeletal muscle and the potential role for resistance training in
      treating the associated dysfunction in bone.

PMID- 22474583
TI  - Translational science and evidence-based healthcare: a clarification and
      reconceptualization of how knowledge is generated and used in healthcare.
AB  - The importance of basing health policy and health care practices on the best
      available international evidence ("evidence-based health care") and on
      translating knowledge or evidence into action ("translation science" or
      "translational research") is increasingly being emphasized across all health
      sectors inmost countries. Evidence-based healthcare is a process that identifies
      policy or clinical questions and addresses these questions by generating
      knowledge and evidence to effectively and appropriately deliver healthcare in
      ways that are effective, feasible, and meaningful to specific populations,
      cultures, and settings. This evidence is then appraised, synthesized, and
      transferred to service delivery settings and health professionals who then
      utilize it and evaluate its impact on health outcomes, health systems, and
      professional practice. Many of the common theories that address this
      translational process place it apart from the evidence-based practice cycle and
      most recognise only two translational gaps. This paper seeks to clarify the
      nature of evidence-based healthcare and translation science and proposes a
      reconceptualization that both brings together these two dominant ideas in modern
      healthcare and asserts the existence of a third fundamental gap that is rarely
      addressed the gap between knowledge need and discovery.

PMID- 22474584
TI  - A Qualitative Study of Patients' Attitudes toward HIV Testing in the Dental
      Setting.
AB  - An estimated 1.1 million people in the USA are living with HIV/AIDS. Nearly
      200,000 of these individuals do not know that they are infected. In 2006, the CDC
      recommended that all healthcare providers routinely offer HIV screening to
      adolescent and adult patients. Nurse-dentist collaborations present unique
      opportunities to provide rapid oral HIV screening to patients in dental clinic
      settings and reach the many adults who lack primary medical providers. However,
      little is known about the feasibility and acceptability of this type of
      innovative practice. Thus, elicitation research was undertaken with dental
      providers, students, and patients. This paper reports the results of qualitative
      interviews with 19 adults attending a university-based dental clinic in New York
      City. Overall, patients held very positive attitudes and beliefs toward HIV
      screening in dental sites and identified important factors that should be
      incorporated into the design of nurse-dentist collaborative HIV screening
      programs.

PMID- 22474585
TI  - Total laparoscopic hysterectomy: evaluation of an evidence-based educational
      strategy using a novel simulated suture and knot-tying challenge, the
      "holiotomy".
AB  - Objective. The purpose of this study was to evaluate perceptions of skills and
      practice patterns of gynecologists attending a course on total laparoscopic
      hysterectomy (TLH). This course employed extensive use of pelvic trainer boxes to
      accomplish the Holiotomy Challenge. The "Holiotomy Challenge" entailed suturing
      two plastic pieces with six figure-of-N sutures tied with four square knots each.
      Methods. A survey was administered before the course and 3 months later. Data
      were analyzed by paired t-tests, McNemar's Chi Squares, and ANCOVAs with
      significance set P < .05. Results. At baseline, 216 surgeons and at 3 months 102
      surgeons returned the survey. Surgeons' self-perceptions of their skills
      significantly increased from 6.24 to 7.28. Their reports of their surgical
      practice at home revealed significantly increased rates of minimally invasive
      procedures, from 42% to 54%. Significantly more surgeons reported having the
      ability to close the vagina, or a small cystotomy or enterotomy. Participation in
      the cadaver lab and presence of their practice partner did not impact these
      rates. Conclusions. A comprehensive course employing laparoscopic surgical
      simulation focused on basic surgical skills essential to TLH has a positive
      impact on attendees' self-rated skill level and rate of laparoscopic approaches.
      Many had begun performing TLH after the course.

PMID- 22474586
TI  - Laparoscopic management of intra-abdominal testis: 5-year single-centre
      experience-a retrospective descriptive study.
AB  - Background. Undescended testis is one of the most common urological problems in
      children, affecting about 1% of boys at age of 1 year. Of these, about 20% have a
      nonpalpable testis with a very high probability that the testis is absent. This
      may have a significant impact on the possibility of malignancy in these testes,
      as well as on the later fertility of these subjects. Methods. We retrospectively
      analyzed the demographic and clinical findings, as well as immediate and 6-month
      outcomes, in 91 patients diagnosed with impalpable undescended testes between
      January 2006 and December 2010. Results. Of the 91 patients, 9 had bilateral and
      82 had unilateral impalpable testes. All 100 testes were managed
      laparoscopically. The largest group of intra-abdominal testes in this series, 42
      testes, was entering the internal ring; in these, laparoscopic exploration and
      standard open orchiopexy resulted in a 66% success rate. The total success rate
      was 63.3%. Conclusion. Laparoscopy is extremely useful in both the diagnosis and
      treatment of impalpable testes. Objectively measured mobility of the testis
      towards the contralateral internal inguinal ring is an excellent intraoperative
      indicator for type of orchiopexy. Standardization of management may increase the
      success rate of orchiopexy.

PMID- 22474587
TI  - Disruption of the serotonergic system after neonatal hypoxia-ischemia in a rodent
      model.
AB  - Identifying which specific neuronal phenotypes are vulnerable to neonatal hypoxia
      ischemia, where in the brain they are damaged, and the mechanisms that produce
      neuronal losses are critical to determine the anatomical substrates responsible
      for neurological impairments in hypoxic-ischemic brain-injured neonates. Here we
      describe our current work investigating how the serotonergic network in the brain
      is disrupted in a rodent model of preterm hypoxia-ischemia. One week after
      postnatal day 3 hypoxia-ischemia, losses of serotonergic raphe neurons,
      reductions in serotonin levels in the brain, and reduced serotonin transporter
      expression are evident. These changes can be prevented using two anti
      inflammatory interventions; the postinsult administration of minocycline or
      ibuprofen. However, each drug has its own limitations and benefits for use in
      neonates to stem damage to the serotonergic network after hypoxia-ischemia. By
      understanding the fundamental mechanisms underpinning hypoxia-ischemia-induced
      serotonergic damage we will hopefully move closer to developing a successful
      clinical intervention to treat neonatal brain injury.

PMID- 22474588
TI  - Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent
      models: implications for sex-specific neuroprotection in clinical neonatal
      practice.
AB  - Clinical findings show that male infants with hypoxic-ischemic injury (HI) fare
      more poorly than matched females on cognitive outcomes. Rodent models of neonatal
      hypoxia-ischemia support this difference, with data showing that perinatal brain
      injury leads to long-term behavioral deficits primarily in male rodents and in
      female rodents treated with early androgens. Results support the idea that sex
      specific gonadal hormones may modulate developmental response to injury and
      dovetail with overwhelming evidence of developmental androgen effects on typical
      brain morphology and behavior. However, mechanisms underlying sex differences in
      response to early brain injury may be more complicated. Specifically, activation
      of cell death pathways in response to HI may also differ by sex. In females, the
      preferential activation of the caspase-dependent apoptotic pathway may actually
      afford greater protection, potentially due to the actions of X-linked inhibitor
      of apoptosis (XIAP) within this pathway. This contrasts the pattern of
      preferential activation of the caspase-independent pathway in males. While an
      integrated model of sex-specific hormonal and genetic modulation of response to
      early injury remains to be fully elucidated, these findings suggest that infants
      might benefit from sex-specific neuroprotection following HI injury.

PMID- 22474589
TI  - Plasma exchange in severe attacks of neuromyelitis optica.
AB  - Background. Neuromyelitis optica (NMO) attacks are poorly controlled by steroids
      and evolve in stepwise neurological impairments. Assuming the strong humoral
      response underlying NMO attacks, plasma exchange (PLEX) is an appropriate
      technique in severe NMO attacks. Objective. Presenting an up-to-date review of
      the literature of PLEX in NMO. Methods. We summarize the rationale of PLEX in
      relation with the physiology of NMO, the main technical aspects, and the
      available studies. Results. PLEX in severe attacks from myelitis or optic
      neuritis are associated with a better outcome, depending on PLEX delay ("time is
      cord and eyes"). NMO-IgG status has no influence. Finally, we build up an
      original concept linking the inner dynamic of the lesion, the timing of PLEX
      onset and the expected clinical results. Conclusion. PLEX is a safe and efficient
      add-on therapy in NMO, in synergy with steroids. Large therapeutic trials are
      required to definitely assess the procedure and define the time opportunity
      window.

PMID- 22474590
TI  - 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the
      Management of Aggressive Non-Hodgkin's B-Cell Lymphoma.
AB  - 18-Fluorodeoxyglucose (FDG-PET/CT) is an established imaging modality that has
      been proven to be of benefit in the management of aggressive B-cell non-Hodgkin's
      lymphoma, such as diffuse large B-cell lymphoma and advanced stage follicular
      lymphoma. The combination of anatomic and functional imaging afforded by FDG
      PET/CT has led to superior sensitivity and specificity in the primary staging,
      restaging, and assessment of response to treatment of hematological malignancies
      when compared to FDG-PET and CT alone. The use of FDG-PET/CT for posttreatment
      surveillance imaging remains controversial, and further study is needed to
      ascertain whether this modality is cost effective and appropriate for use in this
      setting.

PMID- 22474592
TI  - Prediction of outcomes for emergency cervical cerclage in the presence of
      protruding membranes.
AB  - The aim of our study is to verify whether some maternal features are related to
      pregnancy outcomes of emergency cerclage when membranes are protruding through
      the dilated cervix. We present a retrospective review of 20 cases of emergency
      cervical cerclage performed over a 3-year period at Al Wasl hospital, a tertiary
      level centre in Dubai. Analysis shows presence of membrane prolapse with
      infection causing rupture of membranes, to be the strongest predictor of poor
      outcome. Analysis also reveals a significant association between initial white
      blood cell count and perinatal outcome. This information is helpful in decision
      making and counseling patients regarding the likely outcome.

PMID- 22474591
TI  - Ovarian reserve assessment for infertility investigation.
AB  - The current trends to postpone motherhood and the increase in demand for
      assistance in reproductive medicine highlight the need for seeking guidelines for
      the establishment of individualized treatment protocols. Currently available
      ovarian reserve tests do not provide sufficient evidence to be solely considered
      ideal, but they may occupy important place in initial counseling, predicting
      unsatisfactory results that could be improved by individualized induction schemes
      and reducing excessive psychological and financial burdens, and adverse effects.
      In this paper, we revise the role of hormonal basal and dynamic tests, as well as
      ultrasonographic markers, as ovarian reserve markers, in order to provide
      embasement for propaedeutic strategies and their interpretation in order to have
      reproductive success.

PMID- 22474593
TI  - Incidence of Metabolic Syndrome and Its Risk Factors among Type 2 Diabetes Clinic
      Attenders in Isfahan, Iran.
AB  - Aim. At present, little data exist about incidence and the risk factors
      associated with metabolic syndrome (MetS) in patients with type 2 diabetes
      mellitus (T2DM). The objectives of present study were to assess the incidence and
      risk factors of MetS in people with T2DM. Methods. During the mean (SD) follow-up
      period of 11.7 (4.8) years, 3,047 patients with T2DM and free of MetS at baseline
      have been examined to determine incidence and predictors of progression to MetS.
      A modified the National Cholesterol Education Program-Adult Treatment Panel III
      definition with body mass index (BMI) instead of waist circumference was used for
      the MetS. Results. The prevalence of MetS was 63.2% (95% CI: 62.3, 64.1). The
      incidence of MetS was 28.5 (95% CI: 26.8, 30.2) (25.9 men and 30.9 women) per
      1,000 patient-years based on 35,677 patient-years of follow-up. Multivariate
      analysis revealed that higher BMI and education, lower HbA(1c) and treatment with
      oral agent or insulin were associated with MetS. Conclusion. These are the first
      estimate of incidence and risk factors of MetS in patients with T2DM in Iran.
      These findings showed that the natural course of MetS is dynamic. The clinical
      management of patients with T2DM will contribute significantly to MetS
      prevention.

PMID- 22474594
TI  - Characterization of stanniocalcin-1 receptors in the rainbow trout.
AB  - Mammalian stanniocalcin-1 (STC-1) is one of several ligands targeted to
      mitochondria. High affinity STC-1 receptors are present on the mitochondrial
      membranes of nephron cells, myocytes, and hepatocytes, to enable ligand
      sequestration within the matrix. However, STC-1 receptors have not been
      characterized in fish. Nor is it known if mitochondrial targeting occurs in fish.
      The aim of the study was to address these questions. Saturation binding assays
      were carried out to obtain estimates of K(D) and B(max). They revealed the
      presence of saturable, high-affinity receptors on both membranes and mitochondria
      of liver, muscle, and gill filament. In situ ligand binding (ISLB) was used to
      localize receptors at the histological level and revealed some unexpected
      findings. In cranium, for instance, receptors were found mainly in the cartilage
      matrix, as opposed to the chondrocytes. In brain, the majority of receptors were
      located on neuropil areas as opposed to neuronal cell bodies. In skeletal muscle,
      receptors were confined to periodic striations, tentatively identified as the Z
      lines. Receptors were even found on STC-1 producing corpuscles of Stannius cells,
      raising the possibility of there being an autocrine feedback loop or, perhaps, a
      soluble binding protein that is released with the ligand to regulate its
      bioavailability.

PMID- 22474596
TI  - Downregulation in GATA4 and Downstream Structural and Contractile Genes in the
      db/db Mouse Heart.
AB  - Reduced expression of GATA4, a transcriptional factor for structural and
      cardioprotective genes, has been proposed as a factor contributing to the
      development of cardiomyopathy. We investigated whether the reduction of cardiac
      GATA4 expression reported in diabetes alters the expression of downstream genes,
      namely, atrial natriuretic peptide (ANP), B-type natriuretic, peptide (BNP), and
      alpha- and beta-myosin heavy chain (MHC). db/db mice, a model of type 2 diabetes,
      with lean littermates serving as controls, were studied. db/db mice exhibited
      obesity, hyperglycemia, and reduced protein expression of cardiac GLUT4 and IRAP
      (insulin-regulated aminopeptidase), the structural protein cosecreted with GLUT4.
      Hearts from db/db mice had reduced protein expression of GATA4 (~35%) with
      accompanying reductions in mRNA expression of ANP (~40%), BNP (~85%), and alpha
      MHC mRNA (~50%) whereas expression of beta-MHC mRNA was increased by ~60%. Low
      GATA4 was not explained by an increased ligase or atrogin1 expression. CHIP
      protein content was modestly downregulated (27%) in db/db mice whereas mRNA and
      protein expression of the CHIP cochaperone HSP70 was significantly decreased in
      db/db hearts. Our results indicate that low GATA4 in db/db mouse heart is
      accompanied by reduced expression of GATA4-regulated cardioprotective and
      structural genes, which may explain the development of cardiomyopathy in
      diabetes.

PMID- 22474597
TI  - Evaluation of Acute and Chronic Toxicities of the Water Extract from Ziziphus
      attopensis Pierre.
AB  - We studied an acute and chronic oral toxicity of the extract from Ziziphus
      attopensis (ZA) in male and female SD rats according to the OECD guidelines.
      After a single oral administration of ZA 5 g/kg body weight, measurement of the
      body and organs, necropsy, and health monitoring were performed. The body and
      organ weights and behavior were not changed relative to the control rats
      indicating that ZA does not produce acute toxicity. The chronic toxicity was
      determined by oral feeding both male and female rats daily with ZA at the doses
      of 1, 2, 4, and 8 g/kg body weight for 180 days. Body weight changes,
      hematological and biochemical parameters, organ weights, gross finding, and
      histopathology examination were monitored during the experimental period. The
      results did not show any differences from the control groups. Analyses of these
      results with the information of signs, behavior, and health monitoring can lead
      to a conclusion that the long-term oral administration of ZA for 180 days does
      not cause chronic toxicity.

PMID- 22474595
TI  - Recent advances in obesity: genetics and beyond.
AB  - The prevalence of obesity, which is a heritable trait that arises from the
      interactions of multiple genes and lifestyle factors, continues to increase
      worldwide, causing serious health problems and imposing a substantial economic
      burden on societies. For the past several years, various genetic epidemiological
      approaches have been utilized to identify genetic loci for obesity. Recent
      evidence suggests that development of obesity involves hormones and
      neurotransmitters (such as leptin, cocaine- and amphetamine-regulated transcript
      (CART), and ghrelin) that regulate appetite and energy expenditure. These
      hormones act on specific centers in the brain that regulate the sensations of
      satiety. Mutations in these hormones or their receptors can lead to obesity.
      Aberrant circadian rhythms and biochemical pathways in peripheral organs or
      tissues have also been implicated in the pathology of obesity. More
      interestingly, increasing evidence indicates a potential relation between obesity
      and central nervous system disorders (such as cognitive deficits). This paper
      discusses recent advances in the field of genetics of obesity with an emphasis on
      several established loci that influence obesity. These recently identified loci
      may hold the promise to substantially improve our insights into the
      pathophysiology of obesity and open up new therapeutic strategies to combat
      growing obesity epidemic facing the human population today.

PMID- 22474598
TI  - Evaluation of oxidative stress and antioxidant status in patients with
      cardiovascular disease in rural populations of the nilgiris, South India.
AB  - Objective. The objective of this work was to study the risk factors of ischaemic
      heart disease (IHD) in rural populations of the Nilgiris, south India, with
      stress on the various social habits and oxidant stress. Methods. A total of 72
      patients with cardiovascular disease (CVD) and 12 healthy volunteers were
      screened. Forty-seven patients with CVD (intervention group) and 10 healthy
      volunteers (control group) were randomly selected for the study. Written informed
      consent was obtained from all the participants, and their demographic details
      were collected. A 6 mL blood sample was collected from each of the participants,
      and the serum was separated in the samples. The levels of enzymic (superoxide
      dismutase, catalase) and nonenzymic antioxidants (ascorbic acid) in the plasma
      were determined biochemically. The level of thiobarbituric acid species (TBARS),
      which is a predictor of lipid peroxidation, was measured. Results. The
      participants of the study were stratified as according to demographic and social
      variables. The values of all the antioxidants and TBARS were statistically
      compared. Significantly reduced antioxidant levels and increased TBARS levels
      were found in the intervention group compared with the control group. The results
      suggest that the lowered antioxidant level may be a result of the oxidant stress
      of the disease. Statistically significant differences were not found in the
      antioxidant and TBARS levels when comparing smokers versus nonsmokers, alcoholics
      versus nonalcoholics, and vegetarians versus nonvegetarians. Conclusion. The
      major causes of CVD amongst the rural populations of the Nilgiris, south India,
      are preventable causes such as smoking and high fat intake, all of which cause
      oxidative stress, as seen in our study through various serum markers.

PMID- 22474599
TI  - Amelioration of obesity, glucose intolerance, and oxidative stress in high-fat
      diet and low-dose streptozotocin-induced diabetic rats by combination consisting
      of "curcumin with piperine and quercetin".
AB  - Curcumin is an important nutraceutical that has enormous potential for a variety
      of diseases, but the medicinal properties of curcumin cannot be utilized due to
      its low in vivo bioavailability. Therefore, in view of the foregoing, there is an
      extensive need for combinatorial extract "curcumin with piperine and quercetin"
      which may enhance bioavailability of oral curcumin by inhibiting the enzymes
      responsible for the metabolism of curcumin. Thus, the present study investigated
      the effect of combinatorial extract of curcumin on obesity, glucose intolerance,
      and oxidative stress in high fat diet and low-dose streptozotocin-induced rats.
      Oral administration of combinatorial extract for 28 days significantly (P < 0.05)
      reduced PGL (64.84%), PTG (88.94%), LDL (26.38%) and PTC (50.23%) levels,
      respectively and improved glucose tolerance (P < 0.05) significantly to
      exogenously administered glucose (2 g/kg) at 60, 90, and 120 min interval on
      OGTT. The results for antioxidant potential indicate that at 100 mg/kg dose of
      combinatorial extract of curcumin significantly prevented the high-fat diet and
      low-dose streptozotocin-induced changes in the oxidative stress parameters (P <
      0.01) which supports popular medicinal uses of this combinatorial extract as
      antihyperglycemic and hypolipidemic and is likely to bring this promising natural
      product to the forefront of therapeutic agents in the in the treatment of
      "metabolic syndrome".

PMID- 22474600
TI  - Postambulatory hand swelling (big hand syndrome): prevalence, demographics, and
      association with dog walking.
AB  - Introduction. Postambulatory hand swelling (PAHS) seems to be common in the
      general population. There are few mention in the medical literature. The
      objective were (1) to identify prevalence; (2) to compare gender and age groups;
      (3) to determine if dog owners and walkers are more or less prone. Materials and
      Methods. 1009 semirandomly surveys were completed from walkers. Age, gender, and
      dog ownership were assessed. We discussed, among dog owners, whether or not they
      walk their dog regularly, whether or not they notice swollen hands after walking,
      and, if so, if the swelling resolves over 24 hours or persists. Results. 699
      females and 410 males, among whom, 28.9% of females but only 16.3% of males
      reported PAHS (P < 0.001). Surprisingly, those with swelling were statistically
      younger than those without (49.2 versus 52.8 years, P = 0.003), and dog owners
      were more likely than nonowners to report swelling (28.1% versus 21.7%; P =
      0.015). In terms of persistent swelling, this was observed in twice the
      percentage of females as males (13.3 versus 6.5%) and tended to involve older
      subjects (54.0 versus 48.8 years), but with no statistical difference
      significance. Conclusions. PAHS is a relatively common phenomenon, seemingly more
      common in females.

PMID- 22474601
TI  - Stroke in young adults: a prospective study from northwestern Nigeria.
AB  - Background. Stroke is an important cause of morbidity and mortality in young
      adults especially in developing countries. This two-centre prospective study
      aimed at reviewing the pattern, types, and case fatality of stroke in the young
      adults in Northwestern part of Nigeria. Methods. Consecutive patients aged 18-40
      years admitted to the medical wards of two tertiary hospitals from June 2008 to
      August 2010 were recruited. Relevant clinical data were obtained from the
      patients.The survivors were followed up in neurology clinics for 6 months.
      Results. A total of 71 patients aged 18-40 yrs, (mean age was 31.9 +/- 6)
      comprising 52(73%) males and 19(23%) females were enrolled. Forty two (59.1%)
      patients had infarctive stroke. The risk factors included hypertension (74.7%)
      patients, smoking (50.7%), hypercholesterolemia (9.9%), non-hypertensive cardiac
      diseases (8.5%), HIV (8.5%), diabetes mellitus (4.2%) cocaine and amphetamine
      (2.8%), and sickle cell disease (2.8%). Only twelve (17%) patients presented
      within the first 6 hours of onset of stroke. Seventeen (23.9 %) patients died,
      case fatality in the first 24 and 72 hrs was 4.2% and 19.7%, respectively.
      Conclusion. Our data suggests that stroke in young adults is not as uncommon as
      previously suggested. Hypertension, smoking, hypercholesterolemia, cardiac
      diseases and HIV are the most common risk factors.

PMID- 22474602
TI  - Synapses and dendritic spines as pathogenic targets in Alzheimer's disease.
AB  - Synapses are sites of cell-cell contacts that transmit electrical or chemical
      signals in the brain. Dendritic spines are protrusions on dendritic shaft where
      excitatory synapses are located. Synapses and dendritic spines are dynamic
      structures whose plasticity is thought to underlie learning and memory. No wonder
      neurobiologists are intensively studying mechanisms governing the structural and
      functional plasticity of synapses and dendritic spines in an effort to understand
      and eventually treat neurological disorders manifesting learning and memory
      deficits. One of the best-studied brain disorders that prominently feature
      synaptic and dendritic spine pathology is Alzheimer's disease (AD). Recent
      studies have revealed molecular mechanisms underlying the synapse and spine
      pathology in AD, including a role for mislocalized tau in the postsynaptic
      compartment. Synaptic and dendritic spine pathology is also observed in other
      neurodegenerative disease. It is possible that some common pathogenic mechanisms
      may underlie the synaptic and dendritic spine pathology in neurodegenerative
      diseases.

PMID- 22474603
TI  - Linking epigenetics to human disease and Rett syndrome: the emerging novel and
      challenging concepts in MeCP2 research.
AB  - Epigenetics refer to inheritable changes beyond DNA sequence that control cell
      identity and morphology. Epigenetics play key roles in development and cell fate
      commitments and highly impact the etiology of many human diseases. A well-known
      link between epigenetics and human disease is the X-linked MECP2 gene, mutations
      in which lead to the neurological disorder, Rett Syndrome. Despite the fact that
      MeCP2 was discovered about 20 years ago, our current knowledge about its
      molecular function is not comprehensive. While MeCP2 was originally found to bind
      methylated DNA and interact with repressor complexes to inhibit and silence its
      genomic targets, recent studies have challenged this idea. Indeed, depending on
      its interacting protein partners and target genes, MeCP2 can act either as an
      activator or as a repressor. Furthermore, it is becoming evident that although
      Rett Syndrome is a progressive and postnatal neurological disorder, the
      consequences of MeCP2 deficiencies initiate much earlier and before birth. To
      comprehend the novel and challenging concepts in MeCP2 research and to design
      effective therapeutic strategies for Rett Syndrome, a targeted collaborative
      effort from scientists in multiple research areas to clinicians is required.

PMID- 22474605
TI  - Efficient Nonviral Gene Therapy Using Folate-Targeted Chitosan-DNA Nanoparticles
      In Vitro.
AB  - Nonviral cationic polymers like chitosan can be combined with DNA to protect it
      from degradation. The chitosan is a biocompatible, biodegradable, nontoxic, and
      cheap polycationic polymer with low immunogenicity. The objective of this study
      was to synthesize and then assess different chitosan-DNA nanoparticles and to
      select the best ones for selective in vitro transfection in human epidermoid
      carcinoma (KB) cell lines. It revealed that different combinations of molecular
      weight, the presence or absence of folic acid ligand, and different plasmid DNA
      sizes can lead to nanoparticles with various diameters and diverse transfection
      efficiencies. The intracellular trafficking, nuclear uptake, and localization are
      also studied by confocal microscopy, which confirmed that DNA was delivered to
      cell nuclei to be expressed.

PMID- 22474604
TI  - NGF, brain and behavioral plasticity.
AB  - Nerve Growth Factor (NGF) was initially studied for its role as a key player in
      the regulation of peripheral innervations. However, the successive finding of its
      release in the bloodstream of male mice following aggressive encounters and its
      presence in the central nervous system led to the hypothesis that variations in
      brain NGF levels, caused by psychosocial stressor, and the related alterations in
      emotionality, could be functional to the development of proper strategies to cope
      with the stressor itself and thus to survive. Years later this vision is still
      relevant, and the body of evidence on the role of NGF has been strengthened and
      expanded from trophic factor playing a role in brain growth and differentiation
      to a much more complex messenger, involved in psychoneuroendocrine plasticity.

PMID- 22474606
TI  - Modulating Anti-MicroRNA-21 Activity and Specificity Using Oligonucleotide
      Derivatives and Length Optimization.
AB  - MicroRNAs are short, endogenous RNAs that direct posttranscriptional regulation
      of gene expression vital for many developmental and cellular functions.
      Implicated in the pathogenesis of several human diseases, this group of RNAs
      provides interesting targets for therapeutic intervention. Anti-microRNA
      oligonucleotides constitute a class of synthetic antisense oligonucleotides used
      to interfere with microRNAs. In this study, we investigate the effects of
      chemical modifications and truncations on activity and specificity of anti
      microRNA oligonucleotides targeting microRNA-21. We observed an increased
      activity but reduced specificity when incorporating locked nucleic acid monomers,
      whereas the opposite was observed when introducing unlocked nucleic acid
      monomers. Our data suggest that phosphorothioate anti-microRNA oligonucleotides
      yield a greater activity than their phosphodiester counterparts and that a
      moderate truncation of the anti-microRNA oligonucleotide improves specificity
      without significantly losing activity. These results provide useful insights for
      design of anti-microRNA oligonucleotides to achieve both high activity as well as
      efficient mismatch discrimination.

PMID- 22474607
TI  - Optimizing Druggability through Liposomal Formulations: New Approaches to an Old
      Concept.
AB  - Developing innovative delivery strategies remains an ongoing task to improve both
      efficacy and safety of drug-based therapy. Nanomedicine is now a promising field
      of investigation, rising high expectancies for treating various diseases such as
      malignancies. Putting drugs into liposome is an old story that started in the
      late 1960s. Because of the near-total biocompatibility of their lipidic bilayer,
      liposomes are less concerned with the safety issue related to the possible long
      term accumulation in the body of most nanoobjects currently developed in
      nanomedicine. Additionally, novel techniques and recent efforts to achieve better
      stability (e.g., through sheddable coating), combined with a higher selectivity
      towards target cells (e.g., by anchoring monoclonal antibodies or incorporating
      phage fusion protein), make new liposomal drugs an attractive and challenging
      opportunity to improve clinical outcome in a variety of disease. This review
      covers the physicochemistry of liposomes and the recent technical improvements in
      the preparation of liposome-encapsulated drugs in regard to the scientific and
      medical stakes.

PMID- 22474608
TI  - Development of film dosage form containing allopurinol for prevention and
      treatment of oral mucositis.
AB  - Film dosage forms (FDs) containing allopurinol (AP) were prepared using a casting
      method with water-soluble polysaccharides, such as sodium alginate (ALG), and the
      release profile of AP from FDs was investigated in limited dissolution medium.
      Some ALGs were able to form FDs incorporating AP, and the thickness was about 50
      MUm. All FDs were easy to handle, though the rheological properties varied with
      ALG species. AP was homogenously present throughout the FDs and was released with
      disintegration in 10 mL of physiological saline. These results confirmed that FDs
      are useful for preventing or treating localized problems in the oral cavity, such
      as mucositis. FDs are also useful for administering drugs to cancer patients
      receiving chemotherapy and/or radiotherapy.

PMID- 22474609
TI  - The neuropsychological profile of Alzheimer disease.
AB  - Neuropsychological assessment has featured prominently over the past 30 years in
      the characterization of dementia associated with Alzheimer disease (AD). Clinical
      neuropsychological methods have identified the earliest, most definitive
      cognitive and behavioral symptoms of illness, contributing to the identification,
      staging, and tracking of disease. With increasing public awareness of dementia,
      disease detection has moved to earlier stages of illness, at a time when deficits
      are both behaviorally and pathologically selective. For reasons that are not well
      understood, early AD pathology frequently targets large-scale neuroanatomical
      networks for episodic memory before other networks that subserve language,
      attention, executive functions, and visuospatial abilities. This chapter reviews
      the pathognomonic neuropsychological features of AD dementia and how these differ
      from "normal," age-related cognitive decline and from other neurodegenerative
      diseases that cause dementia, including cortical Lewy body disease,
      frontotemporal lobar degeneration, and cerebrovascular disease.

PMID- 22474610
TI  - Brain imaging in Alzheimer disease.
AB  - Imaging has played a variety of roles in the study of Alzheimer disease (AD) over
      the past four decades. Initially, computed tomography (CT) and then magnetic
      resonance imaging (MRI) were used diagnostically to rule out other causes of
      dementia. More recently, a variety of imaging modalities including structural and
      functional MRI and positron emission tomography (PET) studies of cerebral
      metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as
      Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of
      patients with AD, and in prodromal and even presymptomatic states that can help
      rule-in the AD pathophysiological process. No one imaging modality can serve all
      purposes as each have unique strengths and weaknesses. These modalities and their
      particular utilities are discussed in this article. The challenge for the future
      will be to combine imaging biomarkers to most efficiently facilitate diagnosis,
      disease staging, and, most importantly, development of effective disease
      modifying therapies.

PMID- 22474612
TI  - Vascular lumen formation.
AB  - The vascular system developed early in evolution. It is required in large
      multicellular organisms for the transport of nutrients, oxygen, and waste
      products to and from tissues. The vascular system is composed of hollow tubes,
      which have a high level of complexity in vertebrates. Vasculogenesis describes
      the de novo formation of blood vessels, e.g., aorta formation in vertebrate
      embryogenesis. In contrast, angiogenesis is the formation of blood vessels from
      preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta.
      Importantly, the lumen of all blood vessels in vertebrates is lined and formed by
      endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes
      place in a cord of endothelial cells. It involves a complex molecular mechanism
      composed of endothelial cell repulsion at the cell-cell contacts within the
      endothelial cell cords, junctional rearrangement, and endothelial cell shape
      change. As the vascular system also participates in the course of many diseases,
      such as cancer, stroke, and myocardial infarction, it is important to understand
      and make use of the molecular mechanisms of blood vessel formation to better
      understand and manipulate the pathomechanisms involved.

PMID- 22474611
TI  - The new era of the lymphatic system: no longer secondary to the blood vascular
      system.
AB  - The blood and lymphatic systems are the two major circulatory systems in our
      body. Although the blood system has been studied extensively, the lymphatic
      system has received much less scientific and medical attention because of its
      elusive morphology and mysterious pathophysiology. However, a series of landmark
      discoveries made in the past decade has begun to change the previous
      misconception of the lymphatic system to be secondary to the more essential blood
      vascular system. In this article, we review the current understanding of the
      development and pathology of the lymphatic system. We hope to convince readers
      that the lymphatic system is no less essential than the blood circulatory system
      for human health and well-being.

PMID- 22474613
TI  - HIV-1 antiretroviral drug therapy.
AB  - The most significant advance in the medical management of HIV-1 infection has
      been the treatment of patients with antiviral drugs, which can suppress HIV-1
      replication to undetectable levels. The discovery of HIV-1 as the causative agent
      of AIDS together with an ever-increasing understanding of the virus replication
      cycle have been instrumental in this effort by providing researchers with the
      knowledge and tools required to prosecute drug discovery efforts focused on
      targeted inhibition with specific pharmacological agents. To date, an arsenal of
      24 Food and Drug Administration (FDA)-approved drugs are available for treatment
      of HIV-1 infections. These drugs are distributed into six distinct classes based
      on their molecular mechanism and resistance profiles: (1) nucleoside-analog
      reverse transcriptase inhibitors (NNRTIs), (2) non-nucleoside reverse
      transcriptase inhibitors (NNRTIs), (3) integrase inhibitors, (4) protease
      inhibitors (PIs), (5) fusion inhibitors, and (6) coreceptor antagonists. In this
      article, we will review the basic principles of antiretroviral drug therapy, the
      mode of drug action, and the factors leading to treatment failure (i.e., drug
      resistance).

PMID- 22474614
TI  - Host genes important to HIV replication and evolution.
AB  - Recent years have seen a significant increase in understanding of the host
      genetic and genomic determinants of susceptibility to HIV-1 infection and disease
      progression, driven in large part by candidate gene studies, genome-wide
      association studies, genome-wide transcriptome analyses, and large-scale in vitro
      genome screens. These studies have identified common variants in some host loci
      that clearly influence disease progression, characterized the scale and dynamics
      of gene and protein expression changes in response to infection, and provided the
      first comprehensive catalogs of genes and pathways involved in viral replication.
      Experimental models of AIDS and studies in natural hosts of primate lentiviruses
      have complemented and in some cases extended these findings. As the relevant
      technology continues to progress, the expectation is that such studies will
      increase in depth (e.g., to include host whole exome and whole genome sequencing)
      and in breadth (in particular, by integrating multiple data types).

PMID- 22474615
TI  - Antigen targets of type 1 diabetes autoimmunity.
AB  - Type 1 diabetes is characterized by recognition of one or more beta-cell proteins
      by the immune system. The list of target antigens in this disease is ever
      increasing and it is conceivable that additional islet autoantigens, possibly
      including pivotal beta-cell targets, remain to be discovered. Many knowledge gaps
      remain with respect to the disorder's pathogenesis, including the cause of loss
      of tolerance to islet autoantigens and an explanation as to why targeting of
      proteins with a distribution of expression beyond beta cells may result in
      selective beta-cell destruction and type 1 diabetes. Yet, our knowledge of beta
      cell autoantigens has already led to translation into tissue-specific immune
      intervention strategies that are currently being assessed in clinical trials for
      their efficacy to halt or delay disease progression to type 1 diabetes, as well
      as to reverse type 1 diabetes. Here we will discuss recently gained insights into
      the identity, biology, structure, and presentation of islet antigens in relation
      to disease heterogeneity and beta-cell destruction.

PMID- 22474616
TI  - The role of autophagy in Parkinson's disease.
AB  - Great progress has been made toward understanding the pathogenesis of Parkinson's
      disease (PD) during the past two decades, mainly as a consequence of the
      discovery of specific gene mutations contributing to the onset of PD. Recently,
      dysregulation of the autophagy pathway has been observed in the brains of PD
      patients and in animal models of PD, indicating the emerging role of autophagy in
      this disease. Indeed, autophagy is increasingly implicated in a number of
      pathophysiologies, including various neurodegenerative diseases. This article
      will lead you through the connection between autophagy and PD by introducing the
      concept and physiological function of autophagy, and the proteins related to
      autosomal dominant and autosomal recessive PD, particularly alpha-synuclein and
      PINK1-PARKIN, as they pertain to autophagy.

PMID- 22474618
TI  - Pluripotent stem cells in research and treatment of hemoglobinopathies.
AB  - Pluripotent stem cells (PSCs) hold great promise for research and treatment of
      hemoglobinopathies. In principle, patient-specific induced pluripotent stem cells
      could be derived from a blood sample, genetically corrected to repair the disease
      causing mutation, differentiated into hematopoietic stem cells (HSCs), and
      returned to the patient to provide a cure through autologous gene and cell
      therapy. However, there are many challenges at each step of this complex
      treatment paradigm. Gene repair is currently inefficient in stem cells, but use
      of zinc finger nucleases and transcription activator-like effector nucleases
      appear to be a major advance. To date, no successful protocol exists for
      differentiating PSCs into definitive HSCs. PSCs can be directly differentiated
      into primitive red blood cells, but not yet in sufficient numbers to enable
      treating patients, and the cost of clinical scale differentiation is
      prohibitively expensive with current differentiation methods and efficiencies.
      Here we review the progress, promise, and remaining hurdles in realizing the
      potential of PSCs for cell therapy.

PMID- 22474619
TI  - Current Pharmacological Management in Juvenile Huntington's Disease.
AB  - SUMMARY BACKGROUND: The clinical presentation of Juvenile Huntington's Disease
      (JHD) can be very different from adult-onset HD with little evidence to guide
      symptomatic management. AIM: To survey the current use of pharmacological
      treatments for JHD. METHODS: Patients were identified through the HD Association,
      Hospital Doctors and the European Huntington's Disease Network REGISTRY study.
      RESULTS: The most commonly prescribed agents were anti-psychotics (24/45), anti
      depressants (17/45) and anti-parkinsonian medications (15/45). 5 patients were
      taking more than 8 medications. CONCLUSIONS: The most commonly prescribed group
      of medication was the anti-psychotic. Many patients were on multiple therapies,
      highlighting the need to rationalise medications.

PMID- 22474620
TI  - What is the purpose of launching World Journal of Orthopedics?
AB  - The first issue of World Journal of Orthopedics (WJO), whose preparatory work was
      initiated on March 11, 2010, will be published on November 18, 2010. The WJO
      Editorial Board has now been established and consists of 114 distinguished
      experts from 26 countries. Our purpose of launching WJO is to publish peer
      reviewed, high-quality articles via an open-access online publishing model,
      thereby acting as a platform for communication between peers and the wider
      public, and maximizing the benefits to editorial board members, authors and
      readers.

PMID- 22474617
TI  - Parkinson's disease: gene therapies.
AB  - With the recent development of effective gene delivery systems, gene therapy for
      the central nervous system is finding novel applications. Here, we review
      existing viral vectors and discuss gene therapy strategies that have been
      proposed for Parkinson's disease. To date, most of the clinical trials were based
      on viral vectors to deliver therapeutic transgenes to neurons within the basal
      ganglia. Initial trials used genes to relieve the major motor symptoms caused by
      nigrostriatal degeneration. Although these new genetic approaches still need to
      prove more effective than existing symptomatic treatments, there is a need for
      disease-modifying strategies. The investigation of the genetic factors implicated
      in Parkinson's disease is providing precious insights in disease pathology that,
      combined with innovative gene delivery systems, will hopefully offer novel
      opportunities for gene therapy interventions to slow down, or even halt disease
      progression.

PMID- 22474621
TI  - Bone fragility in type 2 diabetes mellitus.
AB  - The number of patients with osteoporosis or type 2 diabetes mellitus (T2DM) is
      increasing in aging and westernized societies. Both disorders predispose elderly
      people to disabling conditions by causing fractures and vascular complications,
      respectively. Recent animal studies have shown that administration of
      osteocalcin, which is specifically secreted from osteoblasts, can increase
      insulin secretion and ameliorate hyperglycemia, obesity, and high triglyceride
      levels in mice fed a high-fat diet. Moreover, several studies have shown that
      antagonism of Wnt signaling by oxidative stress contributes to the development of
      osteoporosis, as well as insulin resistance and hyperlipidemia. Thus, bone
      metabolism and glucose/fat metabolism seem to be etiologically related to each
      other. Meta-analyses of multiple clinical studies in humans have shown that hip
      fracture risk of T2DM patients is increased by 1.4-1.7-fold, although bone
      mineral density (BMD) is not diminished. Vertebral fracture risk of T2DM patients
      is also increased, and BMD is not sensitive enough to assess the risk. These
      findings suggest that bone fragility in T2DM, which is not reflected by BMD,
      depends on bone quality deterioration rather than bone mass reduction. Thus,
      surrogate markers are needed to replace the insensitivity of BMD in assessing
      fracture risks of T2DM patients. Pentosidine, the endogenous secretory receptor
      for advanced glycation endproducts, and insulin-like growth factor-I seem to be
      such candidates, although further studies are required to clarify whether or not
      these markers could predict the occurrence of new fractures of T2DM patients in a
      prospective fashion.

PMID- 22474622
TI  - Portable ultrasonography in mass casualty incidents: The CAVEAT examination.
AB  - Ultrasonography used by practicing clinicians has been shown to be of utility in
      the evaluation of time-sensitive and critical illnesses in a range of
      environments, including pre-hospital triage, emergency department, and critical
      care settings. The increasing availability of light-weight, robust, user
      friendly, and low-cost portable ultrasound equipment is particularly suited for
      use in the physically and temporally challenging environment of a multiple
      casualty incident (MCI). Currently established ultrasound applications used to
      identify potentially lethal thoracic or abdominal conditions offer a base upon
      which rapid, focused protocols using hand-carried emergency ultrasonography could
      be developed. Following a detailed review of the current use of portable
      ultrasonography in military and civilian MCI settings, we propose a protocol for
      sonographic evaluation of the chest, abdomen, vena cava, and extremities for
      acute triage. The protocol is two-tiered, based on the urgency and technical
      difficulty of the sonographic examination. In addition to utilization of well
      established bedside abdominal and thoracic sonography applications, this protocol
      incorporates extremity assessment for long-bone fractures. Studies of the
      proposed protocol will need to be conducted to determine its utility in simulated
      and actual MCI settings.

PMID- 22474623
TI  - Whole body vibration therapy in fracture prevention among adults with chronic
      disease.
AB  - Due to various physical impairments, individuals with chronic diseases often live
      a sedentary lifestyle, which leads to physical de-conditioning. The associated
      muscle weakness, functional decline and bone loss also render these individuals
      highly susceptible to falls and fragility fractures. There is an urgent need to
      search for safe and effective intervention strategies to prevent fragility
      fractures by modifying the fall-related risk factors and enhancing bone health.
      Whole body vibration (WBV) therapy has gained popularity in rehabilitation in
      recent years. In this type of treatment, mechanical vibration is delivered to the
      body while the individual is standing on an oscillating platform. As mechanical
      loading is one of the most powerful stimuli to induce osteogenesis, it is
      proposed that the mechanical stress applied to the human skeleton in WBV therapy
      might be beneficial for enhancing bone mass. Additionally, the vibratory signals
      also constitute a form of sensory stimulation and can induce reflex muscle
      activation, which could potentially induce therapeutic effects on muscle strength
      and important sensorimotor functions such as postural control. Increasing
      research evidence suggests that WBV is effective in enhancing hip bone mineral
      density, muscle strength and balance ability in elderly patients, and could have
      potential for individuals with chronic diseases, who often cannot tolerate
      vigorous impact or resistance exercise training. This article aims to discuss the
      potential role of WBV therapy in the prevention of fragility fractures among
      people with chronic diseases.

PMID- 22474624
TI  - Return to sports activity by athletes after treatment of spondylolysis.
AB  - AIM: To clarify the efficacy of conservative and surgical treatment of
      spondylolysis in athletes. METHODS: PubMed was used to perform a search of the
      literature for studies published during the period from 1990 to 2009 that
      reported data on the outcome of conservative or surgical treatment of
      spondylolysis in athletes. The articles were examined for data on the percentage
      of athletes who returned to sports activities and the interval between the start
      of treatment and their return. RESULTS: Five studies were identified. Two studies
      were concerned with conservative treatment and the other three with surgical
      treatment (wire fixation or screw fixation with bone graft). The percentages of
      athletes who returned to sports activities ranged from 80.0% to 89.3% and from
      81.9% to 100%, respectively, and the intervals until their return ranged from 5.4
      to 5.5 mo and from 7 to 12 mo, respectively. CONCLUSION: The percentages of
      athletes who returned to sports activities after conservative and surgical
      treatment appeared to be satisfactory, but the interval until their return to
      sports activities was longer after surgery than after conservative treatment.

PMID- 22474625
TI  - Management of chronic disruption of the distal tibiofibular syndesmosis.
AB  - Disruption of the distal tibiofibular syndesmosis is frequently accompanied by
      rotational ankle fracture such as pronation-external rotation and rarely occurs
      without ankle fracture. In such injury, not only inadequately treated or
      misdiagnosed cases, but also correctly diagnosed cases can possibly result in a
      chronic pattern which is more troublesome to treat than an acute pattern. This
      paper reviews anatomical and biomechanical characteristics of the distal
      tibiofibular joint, the mechanism of chronic disruption of the distal
      tibiofibular syndesmosis, radiological and arthroscopic diagnosis, and surgical
      treatment.

PMID- 22474626
TI  - Analysis of stress fractures in athletes based on our clinical experience.
AB  - AIM: To analyze stress fractures in athletes based on experience from our sports
      medicine clinic. METHODS: We investigated the association between stress
      fractures and age, sex, sports level, sports activity, and skeletal site in
      athletes seen at our sports medicine clinic between September 1991 and April
      2009. Stress fractures of the pars interarticularis were excluded from this
      analysis. RESULTS: During this period (18 years and 8 mo), 14276 patients (9215
      males and 5061 females) consulted our clinic because of sports-related injuries,
      and 263 patients (1.8%) [171 males (1.9%) and 92 females (1.8%)] sustained stress
      fractures. The average age of the patients with stress fractures was 20.2 years
      (range 10-46 years); 112 patients (42.6%) were 15-19 years of age and 90 (34.2%)
      were 20-24 years of age. Altogether, 90 patients (34.2%) were active at a high
      recreational level and 173 (65.8%) at a competitive level. The highest proportion
      of stress fractures was seen in basketball athletes (21.3%), followed by baseball
      (13.7%), track and field (11.4%), rowing (9.5%), soccer (8.4%), aerobics (5.3%),
      and classical ballet (4.9%). The most common sites of stress fractures in these
      patients were the tibia (44.1%), followed by the rib (14.1%), metatarsal bone
      (12.9%), ulnar olecranon (8.7%) and pelvis (8.4%). The sites of the stress
      fractures varied from sport to sport. The ulnar olecranon was the most common
      stress fracture site in baseball players, and the rib was the most common in
      rowers. Basketball and classical ballet athletes predominantly sustained stress
      fractures of the tibia and metatarsal bone. Track and field and soccer athletes
      predominantly sustained stress fractures of the tibia and pubic bone. Aerobics
      athletes predominantly sustained stress fractures of the tibia. Middle and long
      distance female runners who sustained multiple stress fractures had the female
      athlete triad. CONCLUSION: The results of this analysis showed that stress
      fractures were seen in high-level young athletes, with similar proportions for
      males and females, and that particular sports were associated with specific sites
      for stress fractures. Middle and long distance female runners who suffered from
      multiple stress fractures had the female athlete triad.

PMID- 22474627
TI  - Role of polyethylene particles in peri-prosthetic osteolysis: A review.
AB  - There is convincing evidence that particles produced by the wear of joint
      prostheses are causal in the peri-prosthetic loss of bone, or osteolysis, which,
      if it progresses, leads to the phenomenon of aseptic loosening. It is important
      to fully understand the biology of this bone loss because it threatens prosthesis
      survival, and loosened implants can result in peri-prosthetic fracture, which is
      disastrous for the patient and presents a difficult surgical scenario. The focus
      of this review is the bioactivity of polyethylene (PE) particles, since there is
      evidence that these are major players in the development and progression of
      osteolysis around prostheses which use PE as the bearing surface. The review
      describes the biological consequences of interaction of PE particles with
      macrophages, osteoclasts and cells of the osteoblast lineage, including
      osteocytes. It explores the possible cellular mechanisms of action of PE and
      seeks to use the findings to date to propose potential non-surgical treatments
      for osteolysis. In particular, a non-surgical approach is likely to be applicable
      to implants containing newer, highly cross-linked PEs (HXLPEs), for which
      osteolysis seems to occur with much reduced PE wear compared with conventional
      PEs. The caveat here is that we know little as yet about the bioactivity of HXLPE
      particles and addressing this constitutes our next challenge.

PMID- 22474628
TI  - Current concepts in end-to-side neurorrhaphy.
AB  - In peripheral nerve injury, end-to-side neurorrhaphy involves coaptation of the
      distal stump of a transected nerve to the trunk of an adjacent donor nerve. It
      has been proposed as an alternative technique when the proximal stump of an
      injured nerve is unavailable or the nerve gap is too long to be bridged by a
      nerve graft. Experimental and clinical data suggests that end-to-side
      neurorrhaphy can provide satisfactory functional recovery for the recipient
      nerve, without any deterioration of the donor nerve function. The most accepted
      mechanism of nerve regeneration following end-to-side neurorrhaphy is collateral
      sprouting. The source of the regenerating axons traveling in the epineurium of
      the donor nerve is thought to be the proximal Ranvier's nodes at the site of end
      to-side neurorrhaphy, however, histologic evidence is still lacking. Partial
      neurotomy of the donor nerve may enhance regeneration of motor neurons through
      end-to-side neurorrhaphy and reinnervation of motor targets.

PMID- 22474629
TI  - Classification criteria for spondyloarthropathies.
AB  - Spondyloarthropathies (SpA) are a group of inflammatory arthritis which consist
      of ankylosing spondylitis (AS), reactive arthritis, arthritis/spondylitis
      associated with psoriasis (PsA), and arthritis/spondylitis associated with
      inflammatory bowel diseases. It is now more important than ever to diagnose and
      treat SpA early. New therapeutic agents including blockers of tumor necrosis
      factor have yielded tremendous responses not only in advanced disease but also in
      the early stages of the disease. Sacroiliitis on conventional radiography is the
      result of structural changes which may appear late in the disease process.
      However, magnetic resonance imaging (MRI) can visualize active inflammation at
      sacroiliac joints and spine in recent onset disease. The modified New York
      criteria, the European Spondyloarthropathy Study Group criteria and the Amor
      criteria do not include advanced imaging techniques like MRI which is very
      sensitive to the early Inflammatory changes. Assessment of SpondyloArthritis
      international Society has defined MRI methods for the assessment of sacroiliac
      joints and spine, criteria for inflammatory back pain and developed new criteria
      for classification of axial and peripheral spondyloarthritis. These new criteria
      are intended to be used for patients with SpA at the very early stage of their
      disease. Also, classification of psoriatic arthritis study group developed
      criteria for the classification of PsA. The widespread use of these criteria in
      clinical trials will provide evidence for a better definition of early disease
      and recognize many patients who may further develop classical AS or PsA. These
      efforts will guide therapeutic trials of potent drugs like biological agents in
      the early stage of these diseases.

PMID- 22474630
TI  - Stochastic resonance whole body vibration reduces musculoskeletal pain: A
      randomized controlled trial.
AB  - AIM: To examined the effects of stochastic resonance whole-body vibration
      training on musculoskeletal pain in young healthy individuals. METHODS:
      Participants were 43 undergraduate students of a Swiss University. The study was
      designed as a randomized controlled trial (RCT) with randomized group allocation.
      The RCT consisted of two groups each given 12 training sessions during four weeks
      with either 5 Hz- Training frequency (training condition) or 1.5 Hz Training
      frequency (control condition). Outcome was current musculoskeletal pain assessed
      in the evening on each day during the four week training period. RESULTS:
      Multilevel regression analysis showed musculoskeletal pain was significantly
      decreased in the training condition whereas there was no change in the control
      condition (B = -0.023, SE = 0.010, P = 0.021). Decrease in current
      musculoskeletal pain over four weeks was linear. CONCLUSION: Stochastic resonance
      whole-body vibration reduced musculoskeletal pain in young healthy individuals.
      Stochastic resonance vibration and not any other exercise component within
      training caused pain reduction.

PMID- 22474631
TI  - Ultrasound in the diagnosis of clinical orthopedics: The orthopedic stethoscope.
AB  - Ultrasonography has advantages over other imaging modalities in terms of
      availability and comfort, safety, and diagnostic potential. Operating costs are
      low compared with both computed tomography (CT) and magnetic resonance imaging
      (MRI). The portable equipment is accessible at locations distant from medical
      centers. Importantly, ultrasonography is performed while patients lie in a
      comfortable position, without pain or claustrophobia.

PMID- 22474632
TI  - Interactions between the immune system and bone.
AB  - The relationship between the immune system, estrogen deficiency and bone loss is
      an intriguing and, as yet, unexplained challenge of the past two decades. Here we
      summarize the evidence that links immune cells, inflammation, cytokine production
      and osteoclast formation and activity with particular regard to humans.

PMID- 22474633
TI  - Delayed reconstruction of lateral complex structures of the ankle.
AB  - Lateral ankle instability is one of the most common and well-recognized
      conditions presenting to foot and ankle surgeons. It may exist as an isolated
      entity or in conjunction with other concomitant pathology, making it important to
      appropriately diagnose and identify other conditions that may need to be
      addressed as part of treatment. These associated conditions may be a source of
      chronic pain, even when the instability has been appropriately treated, or may
      lead to failure of treatment by predisposing the patient to ankle inversion
      injuries. The primary goal of this editorial is to provide a brief summary of the
      common techniques used in the delayed reconstruction of lateral ankle ligamentous
      injuries and present a method we have successfully employed for over 15 years. We
      will also briefly discuss the diagnosis and treatment of the more common
      associated conditions, which are important to identify to achieve satisfactory
      results for the patient. We present the outcomes of 250 consecutive
      reconstructions performed over the last 10 years and describe our operative
      technique for addressing lateral ankle ligamentous injuries.

PMID- 22474634
TI  - Effectiveness of exercise for osteoarthritis of the knee: A review of the
      literature.
AB  - Osteoarthritis (OA) of the knee is the most common type of arthritis and the
      major cause of chronic musculoskeletal pain and mobility disability in the
      elderly. The objective of this paper is to discuss the effectiveness of exercise
      for OA of the knee based on a review of the literature. We reviewed the relevant
      literature, i.e. systematic reviews and meta-analyses searched using PubMed.
      Muscle strengthening and aerobic exercises are effective in reducing pain and
      improving physical function in patients with mild to moderate OA of the knee.

PMID- 22474635
TI  - Umbilical cord as a mesenchymal stem cell source for treating joint pathologies.
AB  - Articular cartilage disorders and injuries often result in life-long chronic pain
      and compromised quality of life. Regrettably, the regeneration of articular
      cartilage is a continuing challenge for biomedical research. One of the most
      promising therapeutic approaches is cell-based tissue engineering, which provides
      a healthy population of cells to the injured site but requires differentiated
      chondrocytes from an uninjured site. The use of healthy chondrocytes has been
      found to have limitations. A promising alternative cell population is mesenchymal
      stem cells (MSCs), known to possess excellent proliferation potential and proven
      capability for differentiation into chondrocytes. The "immunosuppressive"
      property of human MSCs makes them an important candidate for allogeneic cell
      therapy. The use of allogeneic MSCs to repair large defects may prove to be an
      alternative to current autologous and allogeneic tissue-grafting procedures. An
      allogeneic cell-based approach would enable MSCs to be isolated from any donor,
      expanded and cryopreserved in allogeneic MSC banks, providing a readily available
      source of progenitors for cell replacement therapy. These possibilities have
      spawned the current exponential growth in stem cell research in pharmaceutical
      and biotechnology communities. Our objective in this review is to summarize the
      knowledge about MSCs from umbilical cord stroma and focus mainly on their
      applications for joint pathologies.

PMID- 22474636
TI  - Diagnosing syndesmotic instability in ankle fractures.
AB  - The precise diagnosis of distal tibiofibular syndesmotic ligament injury is
      challenging and a distinction should be made between syndesmotic ligament
      disruption and real syndesmotic instability. This article summarizes the
      available evidence in the light of the author's opinion. Pre-operative
      radiographic assessment, standard radiographs, computed tomography scanning and
      magnetic resonance imaging are of limited value in detecting syndesmotic
      instability in acute ankle fractures but can be helpful in planning. Intra
      operative stress testing, in the sagittal, coronal or exorotation direction, is
      more reliable in the diagnosis of syndesmotic instability of rotational ankle
      fractures. The Hook or Cotton test is more reliable than the exorotation stress
      test. The lateral view is more reliable than the AP mortise view because of the
      larger displacement in this direction. When the Hook test is used the force
      should be applied in the sagittal direction. A force of 100 N applied to the
      fibula seems to be appropriate. In the case of an unstable joint requiring
      syndesmotic stabilisation, the tibiofibular clear space would exceed 5 mm on the
      lateral stress test. When the surgeon is able to perform an ankle arthroscopy
      this technique is useful to detect syndesmotic injury and can guide anatomic
      reduction of the syndesmosis. Many guidelines formulated in this article are
      based on biomechanical and cadaveric studies and clinical correlation has to be
      established.

PMID- 22474637
TI  - Ultrasound-assisted musculoskeletal procedures: A practical overview of current
      literature.
AB  - Traditionally performed by a small group of highly trained specialists, bedside
      sonographic procedures involving the musculoskeletal system are often delayed
      despite the critical need for timely diagnosis and treatment. Due to this
      limitation, a need evolved for more portability and accessibility to allow
      performance of emergent musculoskeletal procedures by adequately trained non
      radiology personnel. The emergence of ultrasound-assisted bedside techniques and
      increased availability of portable sonography provided such an opportunity in
      select clinical scenarios. This review summarizes the current literature
      describing common ultrasound-based musculoskeletal procedures. In-depth
      discussion of each ultrasound procedure including pertinent technical details,
      indications and contraindications is provided. Despite the limited amount of
      prospective, randomized data in this area, a substantial body of observational
      and retrospective evidence suggests potential benefits from the use of
      musculoskeletal bedside sonography.

PMID- 22474638
TI  - Osteoporotic fracture and parathyroid hormone.
AB  - Osteoporosis and age-related bone loss is associated with changes in bone
      remodeling characterized by decreased bone formation relative to bone resorption,
      resulting in bone fragility and increased risk of fractures. Stimulating the
      function of bone-forming osteoblasts, is the preferred pharmacological
      intervention for osteoporosis. Recombinant parathyroid hormone (PTH), PTH(1-34),
      is an anabolic agent with proven benefits to bone strength and has been
      characterized as a potential therapy for skeletal repair. In spite of PTH's
      clinical use, safety is a major consideration for long-term treatment. Studies
      have demonstrated that intermittent PTH treatment enhances and accelerates the
      skeletal repair process via a number of mechanisms. Recent research into the
      molecular mechanism of PTH action on bone tissue has led to the development of
      PTH analogs to control osteoporotic fractures. This review summarizes a number of
      advances made in the field of PTH and bone fracture to combat these injuries in
      humans and in animal models. The ultimate goal of providing an alternative to
      PTH, currently the sole anabolic therapy in clinical use, to promote bone
      formation and improve bone strength in the aging population is yet to be
      achieved.

PMID- 22474639
TI  - Imaging of the anterior cruciate ligament.
AB  - The anterior cruciate ligament (ACL) is an important structure in maintaining the
      normal biomechanics of the knee and is the most commonly injured knee ligament.
      However, the oblique course of the ACL within the intercondylar fossa limits the
      visualization and assessment of the pathology of the ligament. This pictorial
      essay provides a comprehensive and illustrative review of the anatomy and
      biomechanics as well as updated information on different modalities of
      radiological investigation of ACL, particularly magnetic resonance imaging.

PMID- 22474640
TI  - Methods to shorten the duration of an external fixator in the management of
      tibial infections.
AB  - Massive segmental bone loss due to chronic osteomyelitis represents a
      considerable challenge to orthopedic surgeons and is a limb threatening
      condition. The only option available in such a clinical situation is segment
      transport using the Ilizarov technique of distraction osteogenesis; yet the most
      common problem in cases of bone transport with the Ilizarov technique in massive
      bone loss, is the long duration of the fixator. In addition to autologous bone
      grafting, several mechanical, biologic, and external physical treatment
      modalities may be employed to promote bone formation and maturation during
      segment transport in osteomyelitis patients. Mechanical approaches include
      compressive loading of the distraction regenerate, increased frequency of small
      increments of distraction, and compression-distraction. Intramedullary nailing
      and hemicorticotomy can reduce the time in external fixation; however, these
      techniques are associated with technical difficulties and complications.
      Exogenous application of low-intensity pulsed ultrasound or pulsed
      electromagnetic fields may shorten the duration of external fixation. Other
      promising modalities include diphosphonates, physician-directed use (off-label
      use) of bone morphogenetic proteins, and local injection of bone marrow aspirate
      and platelet gel at the osteotomy site. Well-designed clinical studies are needed
      to establish safe and effective guidelines for various modalities to enhance new
      bone formation during distraction osteogenesis after segment transfer.

PMID- 22474641
TI  - Effect of the amount of battery charge on tube voltage in different hand-held
      dental x-ray systems.
AB  - PURPOSE: Hand-held dental x-ray system is a self contained x-ray machine designed
      to perform intraoral radiography with one or two hands. The issue about its usage
      as general dental radiography is still in dispute. The aim of the present study
      was to assess the relationship between the amount of battery charge and the tube
      voltage in different hand-held dental x-ray systems. MATERIALS AND METHODS: Seven
      hand-held dental x-ray units were used for the study. Tube voltage was measured
      with Unfors ThinX RAD (Unfors Instruments AB, Billdal, Sweden) for 3 consecutive
      exposures at the different amount of battery charge of each unit. The average and
      the deviation percentage of measured kV from indicated kV of each unit were
      calculated. RESULTS: Tube voltage of only 1 unit was 70 kV (indicated by
      manufacturer) and those of the others were 60 kV. Tube voltage deviation
      percentage from the indicated kV at the fully charged battery was from 2.5% to 
      5.5% and from -0.8% to -10.0% at the lowest charged battery. CONCLUSION: Tube
      voltages of all units decreased as the residual amount of the battery charge
      decreased. It is suggested that the performance test for hand-held x-ray system
      should be performed for the minimum residual charged battery as well as the full
      charged one. Persistent battery charging is suggested to maintain the proper tube
      voltage of the hand-held portable x-ray system.

PMID- 22474642
TI  - Anatomical variations of trabecular bone structure in intraoral radiographs using
      fractal and particles count analyses.
AB  - PURPOSE: This study was performed to evaluate possible variations in maxillary
      and mandibular bone texture of normal population using the fractal analysis,
      particles count, and area fraction in intraoral radiographs. MATERIALS AND
      METHODS: Periapical radiographs of patients who had full mouth intraoral
      radiographs were collected. Regions of interest (100*100 pixels) were located
      between the teeth of the maxillary anterior, premolar, and molar area, as well as
      the mandibular anterior, premolar, and molar areas. The fractal dimension (FD)
      was calculated by using the box counting method. The particle count (PC) and area
      fraction (AF) analyses were also performed. RESULTS: There was no significant
      difference in the FD values among the different groups of age, gender, upper, and
      lower jaws. The mean FD value was 1.49+/-0.01. The mean PC ranged from 44 to 54,
      and the mean AF ranged from 10.92 to 11.85. The values of FD, PC, and AF were
      significantly correlated with each other except for the upper molar area.
      CONCLUSION: According to the results, patients with normal trabecular pattern
      showed a FD of approximately 1.5. Based on these results, further investigation
      would be recommended if the FD value of patient significantly differenct from
      this number, since the alteration of this value indicates microstructural
      modification of trabecular pattern of the jaws. Additionally, with periapical
      radiographs, simple and cost-effective, PC and AF could be used to assess the
      deviation from the normal.

PMID- 22474643
TI  - Autologous blood injection to the temporomandibular joint: magnetic resonance
      imaging findings.
AB  - PURPOSE: The aim of this study was to investigate the effect of the autologous
      blood injection (ABI) for chronic recurrent temporomandibular joint (TMJ)
      dislocation using magnetic resonance imaging (MRI). MATERIALS AND METHODS: ABI
      was applied to 14 patients who had chronic recurrent TMJ dislocation. MRIs of the
      patients were taken and compared before and one month after the injection.
      RESULTS: All of the patients had no dislocations of their TMJs on clinical
      examination one month after the injection. In the pre-injection, unilateral or
      bilateral TMJ dislocations were observed on MRIs in all patients. One month after
      the injection, TMJ dislocations were not observed in MRI evaluation of any
      patients. A significant structural change that caused by ABI was not observed.
      CONCLUSION: The procedure was easy to perform and it caused no foreign body
      reaction. However, it was unclear how the procedure prevented the dislocation.

PMID- 22474644
TI  - Diagnostic value of two modes of cone-beam computed tomography in evaluation of
      simulated external root resorption: an in vitro study.
AB  - PURPOSE: Field of view and voxel resolution of cone beam computed tomography
      (CBCT) might affect the diagnostic capability. This study was performed to
      compare between the standard and HiRes zoom modes in the diagnosis of external
      root resorption (ERR) using CBCT. MATERIALS AND METHODS: Sixty three small
      cavities (0.25 mm depth and 0.5 mm diameter) were simulated on the buccal,
      lingual, and proximal surfaces at three different levels of 16 roots of teeth.
      After covering the root with nail varnish, the roots were inserted in the sockets
      and the model was placed in a water-containing lacuna. CBCT scans were taken in
      both standard and HiRes zoom modes using NewTom VG (QR srl Company, Verona,
      Italy). Then, an observer assessed the images to determine the presence or
      absence of the cavities. This process was repeated by increasing the size and
      depth of cavities to 0.5 mm depth and 1 mm diameter. Data were analyzed by
      McNemar test. The sensitivity, specificity, positive predictive value, negative
      predictive value, and likelihood ratio in evaluation of the simulated cavities
      were calculated. RESULTS: There was a significant difference between the two
      imaging modes in diagnosing the shallow cavities (p=0.02).The sensitivity of the
      standard zoom in detecting the shallow cavities was lower than that of the HiRes
      zoom. The likelihood ratio of the HiRes zoom was higher in the diagnosis of both
      cavity types. CONCLUSION: This study suggested that a smaller voxel size in the
      HiRes zoom mode of CBCT is preferred for diagnosis of ERR.

PMID- 22474645
TI  - Evaluation of accuracy of 3D reconstruction images using multi-detector CT and
      cone-beam CT.
AB  - PURPOSE: This study was performed to determine the accuracy of linear
      measurements on three-dimensional (3D) images using multi-detector computed
      tomography (MDCT) and cone-beam computed tomography (CBCT). MATERIALS AND
      METHODS: MDCT and CBCT were performed using 24 dry skulls. Twenty-one
      measurements were taken on the dry skulls using digital caliper. Both types of CT
      data were imported into OnDemand software and identification of landmarks on the
      3D surface rendering images and calculation of linear measurements were
      performed. Reproducibility of the measurements was assessed using repeated
      measures ANOVA and ICC, and the measurements were statistically compared using a
      Student t-test. RESULTS: All assessments under the direct measurement and image
      based measurements on the 3D CT surface rendering images using MDCT and CBCT
      showed no statistically difference under the ICC examination. The measurements
      showed no differences between the direct measurements of dry skull and the image
      based measurements on the 3D CT surface rendering images (P>.05). CONCLUSION:
      Three-dimensional reconstructed surface rendering images using MDCT and CBCT
      would be appropriate for 3D measurements.

PMID- 22474646
TI  - Aneurysmal bone cyst of the mandible managed by conservative surgical therapy
      with preoperative embolization.
AB  - A 9-year-old girl visited our hospital, complaining of a rapid-growing and rigid
      swelling on the left posterior mandibular area. Panoramic radiograph showed a
      moderately defined multilocular honeycomb appearance involving the left
      mandibular body. CT scan revealed an expansile, multilocular osteolytic lesion
      and multiple fluid levels within cystic spaces. Bone scan demonstrated increased
      radiotracer uptake and angiography showed a highly vascularized lesion. The
      lesion was suspected as aneurysmal bone cyst (ABC) and preoperative embolization
      was performed, which minimize the extent of operation and the surgical
      complication. The lesion was treated by surgical curettage and lateral
      decortication with repositioning. No additional treatment such as a surgical
      reconstruction or bone graft was needed. Early diagnosis of ABC is very important
      and appropriate treatment should be performed considering several factors such as
      age, surgical complication, and possibility of recurrence.

PMID- 22474647
TI  - Supernumerary teeth in non-syndromic patients.
AB  - Hyperdontia or supernumerary teeth without associated syndrome is a rare
      phenomenon, as supernumerary teeth are usually associated with cleft lip and
      palate or other syndromes such as Gardner's syndrome, cleidocranial dysplasia,
      and so on. Five patients with supernumerary teeth visited our department. They
      had no familial history or other pathology, certain treatment protocols was
      modified due to the presence of supernumerary teeth. Non-syndromic supernumerary
      teeth, if asymptomatic, need to have periodical radiographic observation. If they
      showed no variation as they impacted in the jaw, careful examination is necessary
      because they may develop into pathological status such as dentigerous cysts. The
      importance of a precise clinical history and radiographic examination for
      patients with multiple supernumerary teeth should be emphasized.

PMID- 22474648
TI  - Unusual intraosseous transmigration of impacted tooth.
AB  - Transmigration of an impacted tooth through the symphyseal suture is a rare and
      special developmental anomaly of unknown etiology that is unique to the
      mandibular canine. Maxillary canine transmigration is even rarer. Transmigrated
      canines are particularly significant due to the aesthetic and functional
      importance. A maxillary lateral incisor crossing the mid-palatal suture has never
      been reported in the literature. The aim of this report is to present the first
      case of simultaneous transmigration of a lateral incisor and canine in the
      maxilla. The paper also reports four unusual cases of unilateral canine
      transmigration in the maxilla and mandible and successful eruption of one of the
      transmigrated mandibular canines following orthodontic traction. Etiology of
      transmigration and its clinical considerations are also discussed.

PMID- 22474649
TI  - Radiological features of familial Gorlin-Goltz syndrome.
AB  - Gorlin-Goltz syndrome is an autosomal dominant disorder principally characterized
      by cutaneous basal cell carcinomas, multiple keratocystic odontogenic tumors, and
      skeletal anomalies. This syndrome may be diagnosed early by dentist because
      keratocystic odontogenic tumors are usually one of the first manifestations of
      the syndrome. Early diagnosis and treatment are of utmost importance in reducing
      the severity of long term sequelae of this syndrome. This report presents a rare
      event of Gorlin-Goltz syndrome occurring in a 39-year-old male and his 8-year-old
      daughter. The clinical and investigative features of this familial disorder has
      been described in detail.

PMID- 22474650
TI  - Keratocystic odontogenic tumor: case report with CT and ultrasonography findings.
AB  - Keratocystic odontogenic tumor (KCOT) is a benign odontogenic tumor with a
      potentially aggressive and infiltrative behavior. KCOT is most commonly occurred
      in mandible and demonstrate a unilocular, round, oval, scalloped radiolucent
      area, while large lesions may appear multilocular. An important characteristic of
      KCOT is its propensity to grow in an antero-posterior direction within medullary
      cavity of bone causing minimal expansion. Definitive diagnosis relies on
      histological examination. In this report, a KCOT that had an expansion both
      buccal and lingual cortical bone is described including its features in computed
      tomography and ultrasonographic exams. The lesion was removed surgically via an
      intraoral approach under local anesthesia and histologically reported as a KCOT.

PMID- 22474651
TI  - A versatile protocol for mRNA electroporation of Xenopus laevis embryos.
AB  - Xenopus laevis is an ideal model system for investigating the mechanisms of
      pattern formation. The ability to express exogenous mRNA or introduce morpholinos
      into cleavage-stage Xenopus embryos has allowed gain- and loss-of-function
      experiments that reveal molecular-genetic control of development and
      regeneration. However, injection of mRNAs into cleavage-stage embryos provides
      limited spatio-temporal control: It is difficult to limit targeting to small
      regions (e.g., inducing foci of expression) and the fate map does not facilitate
      targeting some tissues, such as those of the tail. Likewise, early injection can
      result in unwanted developmental defects because mRNA can be translated long
      before the desired time point. These are especially important limitations when
      studying developmental and regenerative processes during the gastrula to tailbud
      stages. Although transgenic techniques allow precise control over spatio-temporal
      expression of genes when the appropriate promoter is available, the process of
      creating stable transgenic animals is time-consuming. Electroporation provides an
      alternative method for delivering mRNA and other nucleic acids, enabling the
      targeting of single cells or groups of cells at any stage of development. This
      protocol describes detailed electroporation parameters for the transfection of
      mRNA into a wide range of tissues in embryos at gastrula to tailbud stages, with
      high efficiency and expression as early as 4 h post electroporation.

PMID- 22474652
TI  - Measuring resting membrane potential using the fluorescent voltage reporters
      DiBAC4(3) and CC2-DMPE.
AB  - Slow changes in steady-state (resting) transmembrane potential (V(mem)) of non
      excitable cells often encode important instructive signals controlling
      differentiation, proliferation, and cell:cell communication. Probing the function
      of such bioelectric gradients in vivo or in culture requires the ability to track
      V(mem), to characterize endogenous patterns of differential potential, map out
      isopotential cell groups (compartments or cell fields), and confirm the results
      of functional perturbation of V(mem). The use of fluorescent bioelectricity
      reporters (FBRs) has become more common as continuing research and innovation
      have produced better and more options. These dyes are now used routinely for cell
      sorting and for studies of cultured cells. Important advantages over single cell
      electrode measurements are offered by dyes, including: (1) subcellular
      resolution, (2) the ability to monitor multicellular areas and volumes in vivo,
      (3) simplicity of use, (4) ability to measure moving targets, and (5) ability to
      measure over long time periods. Thus, FBRs are suitable for longitudinal studies
      of systems that change and move over time, for example, embryos. Existing
      protocols focus on measurements of rapid action potentials in cultured cells or
      neurons. This article describes a dye pair that can be used to measure resting
      V(mem) in cultured cells and in vivo in Xenopus laevis embryos and tadpoles (and
      is readily applied to other model systems, such as zebrafish, for studies of
      developmental bioelectricity). It is assumed that the reader is fully familiar
      with the process and terminology of fluorescence microscopy.

PMID- 22474653
TI  - General principles for measuring resting membrane potential and ion concentration
      using fluorescent bioelectricity reporters.
AB  - This overview provides the basic information needed to understand, choose, and
      use fluorescent bioelectricity reporters (FBRs), where bioelectricity is defined
      as cell processes that involve ions or ion flux. While traditional methods of
      measuring these characteristics are still valid and necessary, the utility of
      FBRs has facilitated measurement of these properties under circumstances that are
      not possible with microelectrodes. Specifically, these dyes can be used to
      achieve subcellular resolution, to measure many cells simultaneously in vivo, and
      to track bioelectric gradients over long time periods despite cell movements and
      divisions. This article covers the basic principles underlying the interpretation
      of the dye signals, describes essential steps for troubleshooting, optimizing
      data collection, analysis, and presentation, and provides compilations of
      information that are useful for choosing FBRs for particular projects.

PMID- 22474654
TI  - Transmission electron microscopy of thin sections of Drosophila: high-pressure
      freezing and freeze-substitution.
AB  - The state of the art in fine-structure preservation for thin sectioning can be
      achieved by using fast-freezing technology followed by freeze substitution and
      embedding in resin. Samples prepared by high-pressure freezing are estimated to
      be "fixed" in 20-50 msec. Fast freezing also freezes every cell component
      regardless of its chemistry. Once frozen, tissues can be processed in a variety
      of ways before viewing in the electron microscope; here we describe only freeze
      substitution. In freeze substitution, cells are dehydrated at very low
      temperatures and cell water is replaced with organic solvent at -80 degrees C to 
      90 degrees C. At this temperature, large molecules such as proteins are
      immobilized, yet smaller molecules such as water (ice) can be dissolved and
      replaced with organic solvents, e.g., acetone. The ideal way to do freeze
      substitution is with a dedicated freeze-substitution device such as the Leica
      AFS2 system. These devices allow programming of the times and temperatures
      needed. Alternatively, if this equipment is not available, freeze substitution
      can still be performed using items commonly found around the laboratory, as is
      described here. This protocol is useful for preparing thin sections of Drosophila
      when the best possible preservation of ultrastructure and antigenicity is
      required.

PMID- 22474655
TI  - Transmission electron microscopy of thin sections of Drosophila: conventional
      chemical fixation of embryos using trialdehyde.
AB  - High-pressure freezing (HPF) followed by freeze-substitution is a valuable method
      for specimen preservation for transmission electron microscopy (TEM) in
      Drosophila. However, not all projects require this level of precision. In
      addition, some tissues are too large to fit into the HPF specimen carriers, and
      some fly tissues such as eyes and ovaries do not freeze well. This protocol
      describes a trialdehyde fixation procedure for embryos, to be used in situations
      where optimal preservation is not required or when HPF is not an option. Because
      the vitelline membrane is impermeable to aqueous solvents, it is necessary to
      either mechanically disrupt it or render it permeable by treatment with organic
      solvents. Good ultrastructural preservation has been achieved by puncturing
      embryos immersed in fixative with extremely sharp tungsten needles, as described
      here.

PMID- 22474656
TI  - Microsatellite markers for linkage and association studies.
AB  - During the 1990s and the first several years of this century, microsatellites or
      short tandem repeats were the workhorse genetic markers for hypothesis
      independent studies in human genetics, facilitating genome-wide linkage studies
      and allelic imbalance studies. However, the rise of higher throughput and cost
      effective single-nucleotide polymorphism (SNP) platforms led to the era of the
      SNP for genome scans. Nevertheless, it is important to note that microsatellites
      remain highly informative and useful measures of genomic variation for linkage
      and association studies. Their continued advantage in complementing SNPs lies in
      their greater allelic diversity than biallelic SNPs as well as in their
      population history, in which single-step expansion or contraction of the tandem
      repeat on the background of ancestral SNP haplotypes can break up common
      haplotypes, leading to greater haplotype diversity within the linkage
      disequilibrium block of interest. In fact, microsatellites have starred in
      association studies leading to widely replicated discoveries of type 2 diabetes
      (TCF7L2) and prostate cancer genes (the 8q21 region). At the end of the day, it
      will be important to catalog all variation, including SNPs, microsatellites, copy
      number variations, and polymorphic inversions in human genetic studies. This
      article describes the utilities of microsatellites and experimental approaches in
      their use.

PMID- 22474657
TI  - Preparation of vesicular stomatitis virus-G (VSV-G) conjugate and its use in gene
      transfer.
AB  - The fusiogenic envelope G glycoprotein of the vesicular stomatitis virus (VSV-G)
      that has been used to pseudotype retrovirus and lentivirus vectors can be used
      alone as an efficient vehicle for gene transfer. VSV-G protein is secreted into
      the culture medium as sendimentable vesicles from cells transfected with a VSV-G
      expression plasmid in the absence of other viral components. The VSV-G vesicles
      in the conditioned medium can be partially purified by pelleting through sucrose
      cushion ultracentrifugation. Protein-DNA complexes are formed by mixing the VSV-G
      vesicles with naked plasmid DNA. Such complexes show markedly enhanced
      transfection efficiency when added to the culture medium of recipient cells. The
      cell tropism of VSV-G-DNA complex-mediated gene transfer resembles that of VSV-G
      pseudotyped retrovirus and lentivirus vectors, and the complex is therefore
      particularly useful for transfection of cells that are refractory to other
      methods. Still, some cells are refractory to VSV-G-mediated transfection. It
      should also be noted that overdose of VSV-G can be quite toxic to the recipient
      cells. The primitive complexes formed by mixing a viral fusiogenic envelope
      protein with naked DNA may represent a step toward fusing useful features of
      viral and nonviral vectors for safer and more efficient gene transfer. This
      protocol describes simple methods for preparation of VSV-G and for gene transfer
      with DNA-VSV-G complexes.

PMID- 22474658
TI  - Quantifying the Bicoid morphogen gradient in living fly embryos.
AB  - In multicellular organisms, patterns of gene expression are established in
      response to gradients of signaling molecules. During fly development in early
      Drosophila embryos, the Bicoid (Bcd) morphogen gradient is established within the
      first hour after fertilization. Bcd acts as a transcription factor, initiating
      the expression of a cascade of genes that determine the segmentation pattern of
      the embryo, which serves as a blueprint for the future adult organism. A robust
      understanding of the mechanisms that govern this segmentation cascade is still
      lacking, and a new generation of quantitative measurements of the spatiotemporal
      concentration dynamics of the individual players in this cascade is necessary for
      further progress. Here we describe a series of methods that represent the
      beginning of the use of Bcd as a quantification example. We describe the
      generation of a transgenic fly line expressing a Bcd-enhanced green fluorescent
      protein fusion protein. Using two-photon microscopy, we analyze the Bcd
      concentration dynamics and measure absolute Bcd expression levels in living fly
      embryos. These experiments have proven to be fruitful, generating new insights
      into the mechanisms that lead to the establishment and readout of the Bcd
      gradient. Generalization of these methods to other genes in the Drosophila
      segmentation cascade is straightforward and should further our understanding of
      the early patterning processes and the architecture of the underlying genetic
      network structure.

PMID- 22474659
TI  - Microultrasound and its application to longitudinal studies of mouse eye
      development and disease.
AB  - Microultrasound imaging is a flexible high-resolution real-time in vivo imaging
      modality based on the transmission and the reception of ultrasound waves. Because
      of its high temporal (>250 Hz) and spatial (30-150 um) resolutions and the
      noninvasive nature of ultrasound, microultrasound is used extensively in
      preclinical research to monitor functional and dynamic phenotypic changes in
      small animal models. Its ability to perform in vivo longitudinal monitoring of
      development, pathology, and therapeutic effectiveness is particularly
      advantageous. This article reviews the technology and the applications of high
      frequency microultrasound for the study of mouse eye development from embryonic
      day E11.5 to postnatal day P16. Procedures for animal handling and scanning are
      given, and applications are described in the context of ocular development and
      disease. Quantitative analysis of the growth kinetics of the lens and the orbit
      is discussed. In addition, mouse models of retinoblastoma and glaucoma are
      followed as a function of disease progression to reveal their associated
      morphological and functional traits. Microultrasound is performed with high
      frequency imaging equipment (from VisualSonics) operating at center frequencies
      between 15 and 50 MHz. These instruments provide both anatomical imaging as well
      as functional and molecular analyses of the living mouse.

PMID- 22474660
TI  - Presynaptic imaging of projection fibers by in vivo injection of dextran
      conjugated calcium indicators.
AB  - Dextran-conjugated calcium indicators are stably retained within neurons. As a
      result, they are well suited to measuring presynaptic calcium at physiological
      temperatures. In addition, dextran indicators can be used to label neurons and
      their presynaptic boutons in vivo. This has allowed measurements of calcium in
      the presynaptic boutons of projection fibers that cannot be stably loaded with
      other types of indicators. This protocol describes a technique for in vivo
      loading of the climbing fiber projection to the cerebellum with dextran
      conjugated indicators for subsequent presynaptic calcium imaging in brain slices.
      This technique is applicable to studies of projection fibers in many species from
      which brain slices can be prepared. The dextran indicator is injected into the
      inferior olive using a stereotaxic device. After a period of 1-3 d, cerebellar
      slices are prepared and presynaptic calcium transients are measured at
      physiological temperature in labeled climbing fibers. The protocol also discusses
      important considerations for using dextran-conjugated indicators to measure
      presynaptic calcium.

PMID- 22474661
TI  - Multiphoton stimulation of neurons and spines.
AB  - This protocol describes an optical method to directly stimulate a neuron (i.e.,
      without using any caged chemicals or genetic probes) using an infrared ultrafast
      mode-locked laser. This method can trigger action potentials in a targeted neuron
      when a laser beam is applied to the somatic membrane. Alternatively, it can mimic
      excitatory postsynaptic potentials (EPSPs) when applied to dendritic spines. The
      protocol has been applied successfully using juvenile (postnatal day 7-14) C57
      mouse neocortical and hippocampal acute slices (~300-um thickness). It can be
      used in conjunction with slices bulk loaded with calcium indicators, such as Fura
      2 AM.

PMID- 22474662
TI  - In vivo imaging of Drosophila larval neuromuscular junctions to study synapse
      assembly.
AB  - In the past decade, a significant number of proteins involved in the
      developmental assembly and maturation of synapses have been identified. However,
      detailed knowledge of the molecular processes underlying developmental synapse
      assembly is still sparse. Here, we discuss an approach that makes extended in
      vivo imaging of selected proteins in live Drosophila larvae feasible at a single
      synapse resolution. The intact larvae are anesthetized and neuromuscular
      junctions (NMJs) are noninvasively imaged with confocal microscopy. This method
      allows for both protein trafficking and protein turnover kinetics to be studied
      at various points in time during the development of an animal. These data
      contribute to our understanding of synaptic assembly under in vivo conditions.

PMID- 22474663
TI  - Building an imaging chamber for in vivo imaging of Drosophila larvae.
AB  - In the past decade, a significant number of proteins involved in the
      developmental assembly and maturation of synapses have been identified. However,
      detailed knowledge of the molecular processes underlying developmental synapse
      assembly is still sparse. We have developed an approach that makes extended in
      vivo imaging of selected proteins in live Drosophila larvae feasible at a single
      synapse resolution. The intact larvae are anesthetized and noninvasively imaged
      with confocal microscopy. This method allows for both protein trafficking and
      protein turnover kinetics to be studied at various points in time during the
      development of an animal. These data contribute to our understanding of synaptic
      assembly under in vivo conditions. This protocol describes the assembly of the
      imaging chamber needed for in vivo imaging of Drosophila larvae. It also covers
      the construction of an appropriate anesthetization device.

PMID- 22474664
TI  - In vivo imaging of the Drosophila larval neuromuscular junction.
AB  - In the past decade, a significant number of proteins involved in the
      developmental assembly and maturation of synapses have been identified. However,
      detailed knowledge of the molecular processes underlying developmental synapse
      assembly is still sparse. We have developed an approach that makes extended in
      vivo imaging of selected proteins in live Drosophila larvae feasible at a single
      synapse resolution. This protocol describes the repetitive, noninvasive imaging
      of the neuromuscular junction (NMJ) of a live, intact, anesthetized Drosophila
      larva over extended periods of time with confocal microscopy. Proteins of
      interest must be tagged with a fluorescent label and have to be expressed in
      transgenic fly strains. The method has proven highly useful for the study of
      synaptic assembly and the trafficking of proteins. These data contribute to our
      understanding of synaptic assembly under in vivo conditions.

PMID- 22474665
TI  - Quantitative analysis of Drosophila larval neuromuscular junction morphology.
AB  - In the past decade, a significant number of proteins involved in the
      developmental assembly and maturation of synapses have been identified. However,
      detailed knowledge of the molecular processes underlying developmental synapse
      assembly is still sparse. We have developed an approach that makes extended in
      vivo imaging of selected proteins in live Drosophila larvae feasible at a single
      synapse resolution. The intact larvae are anesthetized and neuromuscular
      junctions (NMJs) are noninvasively imaged with confocal microscopy. This method
      allows for both protein trafficking and protein turnover kinetics to be studied
      at various points in time during the development of an animal. These data
      contribute to our understanding of synaptic assembly under in vivo conditions.
      Image analysis and quantification are best performed in three dimensions (3D;
      e.g., with the software Imaris by Bitplane), but they can also be performed using
      a simpler method for two-dimensional (2D) analysis using the free software ImageJ
      as presented in this protocol. We propose various possibilities for how an
      analysis may be performed with ImageJ, rather than providing an inflexible
      protocol, in which the steps must be followed without modifications. Although
      execution of most of the tools will be described via the ImageJ menu, most are
      also readily accessible through icons in ImageJ McMaster Biophotonics Facility
      (MBF) toolsets. These toolsets can also very easily be adapted for higher
      efficiency.

PMID- 22474666
TI  - Polylysine copolymers for gene delivery.
AB  - Polylysine and its copolymers have been extensively used as nonviral polymeric
      gene carriers. Although polylysine on its own is toxic to cells, when
      polyethylene glycol is covalently linked to polylysine, toxicity is reduced and
      DNA transfection efficiency is increased. A degradable polylysine analog,
      polyaminobutyl glycolic acid, has been synthesized. Stearyl polylysine shows
      strong hydrophobic interactions with low-density lipoprotein and these components
      can be combined with DNA to form a "terplex" system that allows delivery of DNA
      to targeted cells and significant levels of transfection both in vitro and in
      vivo.

PMID- 22474667
TI  - In vitro transfection with plasmid DNA using polylysine copolymers.
AB  - The terplex system for delivering DNA to targeted cells comprises three
      components-stearyl polylysine (PLL), low-density lipoprotein (LDL), and DNA. This
      article describes a method for optimizing the relative amounts of these
      components and determining the transfection parameters for a given cell line.

PMID- 22474668
TI  - Cellular imaging using total internal reflection fluorescence microscopy: theory
      and instrumentation.
AB  - Live cell fluorescent microscopy is important in elucidating dynamic cellular
      processes such as cell signaling, membrane trafficking, and cytoskeleton
      remodeling. Often, transient intermediate states are revealed only when imaged
      and quantitated at the single-molecule, vesicle, or organelle level. Such insight
      depends on the spatiotemporal resolution and sensitivity of a given microscopy
      method. Confocal microscopes optically section the cell and improve image
      contrast and axial resolution (>600 nm) compared with conventional
      epifluorescence microscopes. Another approach, which can selectively excite
      fluorophores in an even thinner optical plane (<100 nm) is total internal
      reflection fluorescence microscopy (TIRFM). The key principle of TIRFM is that a
      thin, exponentially decaying, evanescent field of excitation can be generated at
      the interface of two mediums of different refractive index (RI) (e.g., the glass
      coverslip and the biological specimen); as such, TIRFM is ill-suited to deep
      imaging of cells or tissue. However, for processes near the lower cell cortex,
      the sensitivity of TIRFM is exquisite. The recent availability of a very high
      numerical-aperture (NA) objective lens (>1.45) and turnkey TIRFM systems by all
      the major microscopy manufacturers has made TIRFM increasingly accessible and
      attractive to biologists, especially when performed in a quantitative manner and
      complemented with orthogonal genetic and molecular manipulations. This article
      discusses the optical principles of TIRFM (including a sample calculation of
      penetration depth), the components of a TIRFM setup, and the use of TIRFM in
      combination with other imaging modalities.

PMID- 22474669
TI  - Alignment and calibration of total internal reflection fluorescence microscopy
      systems.
AB  - Live cell fluorescent microscopy is important in elucidating dynamic cellular
      processes such as cell signaling, membrane trafficking, and cytoskeleton
      remodeling. Often, transient intermediate states are revealed only when imaged
      and quantitated at the single-molecule, vesicle, or organelle level. Such insight
      depends on the spatiotemporal resolution and sensitivity of a given microscopy
      method. Confocal microscopes optically section the cell and improve image
      contrast and axial resolution (>600 nm) compared with conventional
      epifluorescence microscopes. Another approach, which can selectively excite
      fluorophores in an even thinner optical plane (<100 nm) is total internal
      reflection fluorescence microscopy (TIRFM). The key principle of TIRFM is that a
      thin, exponentially decaying, evanescent field of excitation can be generated at
      the interface of two mediums of different refractive index (RI) (e.g., the glass
      coverslip and the biological specimen); as such, TIRFM is ill-suited to deep
      imaging of cells or tissue. However, for processes near the lower cell cortex,
      the sensitivity of TIRFM is exquisite. The recent availability of a very high
      numerical-aperture (NA) objective lens (>1.45) and turnkey TIRFM systems by all
      the major microscopy manufacturers has made TIRFM increasingly accessible and
      attractive to biologists, especially when performed in a quantitative manner and
      complemented with orthogonal genetic and molecular manipulations. This protocol
      describes the procedure for alignment and calibration of TIRFM systems using
      standard cellular samples. The goal is to correctly collimate and align the TIRF
      illuminator vis-a-vis the downstream optics. For illustration, a 488-nm laser and
      green fluorescent protein (GFP) filter cube are used.

PMID- 22474670
TI  - Generating live cell data using total internal reflection fluorescence
      microscopy.
AB  - Live cell fluorescent microscopy is important in elucidating dynamic cellular
      processes such as cell signaling, membrane trafficking, and cytoskeleton
      remodeling. Often, transient intermediate states are revealed only when imaged
      and quantitated at the single-molecule, vesicle, or organelle level. Such insight
      depends on the spatiotemporal resolution and sensitivity of a given microscopy
      method. Confocal microscopes optically section the cell and improve image
      contrast and axial resolution (>600 nm) compared with conventional
      epifluorescence microscopes. Another approach, which can selectively excite
      fluorophores in an even thinner optical plane (<100 nm) is total internal
      reflection fluorescence microscopy (TIRFM). The key principle of TIRFM is that a
      thin, exponentially decaying, evanescent field of excitation can be generated at
      the interface of two mediums of different refractive index (RI) (e.g., the glass
      coverslip and the biological specimen); as such, TIRFM is ill-suited to deep
      imaging of cells or tissue. However, for processes near the lower cell cortex,
      the sensitivity of TIRFM is exquisite. The recent availability of a very high
      numerical-aperture (NA) objective lens (>1.45) and turnkey TIRFM systems by all
      the major microscopy manufacturers has made TIRFM increasingly accessible and
      attractive to biologists, especially when performed in a quantitative manner and
      complemented with orthogonal genetic and molecular manipulations. This article
      discusses sample preparation for TIRFM, acquisition of time-lapse movies, and
      quantitative analysis. It also gives examples of imaging cytoskeleton dynamics
      and exo- and endocytosis using TIRFM.

PMID- 22474671
TI  - Prostate: registration of digital histopathologic images to in vivo MR images
      acquired by using endorectal receive coil.
AB  - PURPOSE: To develop and evaluate a technique for the registration of in vivo
      prostate magnetic resonance (MR) images to digital histopathologic images by
      using image-guided specimen slicing based on strand-shaped fiducial markers
      relating specimen imaging to histopathologic examination. MATERIALS AND METHODS:
      The study was approved by the institutional review board (the University of
      Western Ontario Health Sciences Research Ethics Board, London, Ontario, Canada),
      and written informed consent was obtained from all patients. This work proposed
      and evaluated a technique utilizing developed fiducial markers and real-time
      three-dimensional visualization in support of image guidance for ex vivo prostate
      specimen slicing parallel to the MR imaging planes prior to digitization,
      simplifying the registration process. Means, standard deviations, root-mean
      square errors, and 95% confidence intervals are reported for all evaluated
      measurements. RESULTS: The slicing error was within the 2.2 mm thickness of the
      diagnostic-quality MR imaging sections, with a tissue block thickness standard
      deviation of 0.2 mm. Rigid registration provided negligible postregistration
      overlap of the smallest clinically important tumors (0.2 cm(3)) at histologic
      examination and MR imaging, whereas the tested nonrigid registration method
      yielded a mean target registration error of 1.1 mm and provided useful
      coregistration of such tumors. CONCLUSION: This method for the registration of
      prostate digital histopathologic images to in vivo MR images acquired by using an
      endorectal receive coil was sufficiently accurate for coregistering the smallest
      clinically important lesions with 95% confidence.

PMID- 22474672
TI  - Obliterative portal venopathy: findings at CT imaging.
AB  - PURPOSE: To retrospectively analyze the computed tomographic (CT) findings in a
      single-center series of adult patients with biopsy-proved obliterative portal
      venopathy (OPV) and to compare them with those observed in patients with
      cirrhosis. MATERIALS AND METHODS: The requirement for informed consent was
      waived. This institutional review board-approved study included 42 consecutive
      patients with a histologically proved diagnosis of OPV who underwent CT at
      diagnosis. The clinical characteristics at diagnosis were recorded, and CT
      examination results were reviewed. Two radiologists evaluated portal vein patency
      and intrahepatic portal branches, the morphologic changes in the liver, the
      presence of hepatic nodules, and signs of portal hypertension in consensus. The
      control group consisted of 42 patients who had histologically proved cirrhosis.
      CT findings were compared between the OPV patient group and the cirrhotic group
      and also among the conditions associated with patients with OPV. The Fisher exact
      test was used. P values of .05 or less were considered to indicate significant
      differences. RESULTS: The following CT findings were observed significantly more
      frequently in OPV than in cirrhosis: extrahepatic portal vein thrombosis (18
      [43%] of 42 vs five [12%] of 42); intrahepatic portal abnormalities (18 [58%] of
      31 vs one [2%] of 42) such as reduced caliber, occlusive thrombosis, and lack of
      visibility; focal nodular hyperplasia-like nodules (six [14%] of 42 vs 0 [0%] of
      42); and perfusion disorders (15 [36%] of 42 vs six [14%] of 42). Conversely, the
      combination of hypertrophy of the caudate lobe and atrophy of segment IV (27
      [64%] of 42 vs 10 [24%] of 42) and nodular surface (37 [88%] of 42 vs seven [17%]
      of 42) were seen significantly more often in cirrhosis. CONCLUSION:
      Characteristic CT findings in patients with OPV that differ from those in
      patients with cirrhosis were shown, the most common being the presence of intra-
      or extrahepatic portal abnormalities.

PMID- 22474673
TI  - Value of the hemorrhage exclusion sign on T1-weighted prostate MR images for the
      detection of prostate cancer.
AB  - PURPOSE: To retrospectively determine the prevalence and positive predictive
      value (PPV) of the hemorrhage exclusion sign on T1-weighted magnetic resonance
      (MR) images in conjunction with findings on T2-weighted images in the detection
      of prostate cancer, with use of whole-mount step-section pathologic specimens
      from prostatectomy as the reference standard. MATERIALS AND METHODS: The
      institutional review board approved this retrospective study, which was compliant
      with HIPAA, and the requirement to obtain informed consent was waived. Two
      hundred ninety-two patients with biopsy-proved prostate cancer underwent
      endorectal MR imaging followed by prostatectomy. The hemorrhage exclusion sign
      was defined as the presence of a well-defined area of low signal intensity
      surrounded by areas of high signal intensity on T1-weighted images. Two readers
      independently assessed the presence and extent of postbiopsy changes and the
      hemorrhage exclusion sign. The presence of a corresponding area of homogeneous
      low signal intensity on T2-weighted images was also recorded. The prevalence and
      PPV of the hemorrhage exclusion sign were calculated. RESULTS: Readers 1 and 2
      found postbiopsy changes in the peripheral zone in 184 (63%) and 189 (64.7%) of
      the 292 patients, respectively. In these patients, the hemorrhage exclusion sign
      was observed in 39 of 184 patients (21.2%) by reader 1 and 36 of 189 patients
      (19.0%) by reader 2. A corresponding area of homogeneous low signal intensity was
      seen on T2-weighted images in the same location as the hemorrhage exclusion sign
      in 23 of 39 patients (59%) by reader 1 and 19 of 36 patients (53%) by reader 2.
      The PPV of the hemorrhage exclusion sign alone was 56% (22 of 39 patients) for
      reader 1 and 50% (18 of 36 patients) for reader 2 but increased to 96% (22 of 23
      patients) and 95% (18 of 19 patients) when the sign was identified in an area of
      homogeneous low signal intensity on T2-weighted images. CONCLUSION: Postbiopsy
      change is a known pitfall in the interpretation of T2-weighted images. The
      authors have shown that a potential benefit of postbiopsy change is the presence
      of excluded hemorrhage, which, in conjunction with a corresponding area of
      homogeneous low signal intensity at T2-weighted imaging, is highly accurate for
      cancer identification.

PMID- 22474674
TI  - River history.
AB  - During the last half century, advances in geomorphology-abetted by conceptual and
      technical developments in geophysics, geochemistry, remote sensing, geodesy,
      computing and ecology-have enhanced the potential value of fluvial history for
      reconstructing erosional and depositional sequences on the Earth and on Mars and
      for evaluating climatic and tectonic changes, the impact of fluvial processes on
      human settlement and health, and the problems faced in managing unstable fluvial
      systems.

PMID- 22474675
TI  - 210Pb geochronology of flood events in large tropical river systems.
AB  - Floodplain sedimentation removes particles from fluvial transport and constructs
      stratigraphic records of flooding, biogeochemical sequestration and other aspects
      of the environmental history of river basins-insight that is enhanced by accurate
      geochronology. The natural fallout radionuclide (210)Pb, often employed to date
      lacustrine and marine sediments, has previously been used to determine floodplain
      accumulation rates over decadal-to-century time scales using the assumption that
      both input concentration and sediment accumulation rates are constant. We test
      this model in approximately 110 cores of pristine floodplains along approximately
      2000 km of the Rios Beni and Mamore in northern Bolivia; over 95 per cent of the
      (210)Pb profiles depict individual episodic deposition events, not steady-state
      accumulation, requiring a revised geochronological methodology. Discrete
      measurements of down-core, clay-normalized adsorbed excess (210)Pb activity are
      coupled with a new conceptual model of (210)Pb input during floods: constant
      initial reach clay activity, unknown sedimentation (CIRCAUS). This enhanced
      methodology yields (210)Pb dates that correspond well with (i) dates determined
      from meteoric caps, (ii) observed dates of river bar formation, (iii) known flood
      dates, and (iv) dates from nearby cores along the same transect. Similar results
      have been found for other large rivers. The CIRCAUS method for geochronology
      therefore offers a flexible and accurate method for dating both episodic (decadal
      recurrence frequency) and constant (annual recurrence) sediment accumulation on
      floodplains.

PMID- 22474676
TI  - Historical sources and watershed evolution.
AB  - Historical data, including structures, documents, photographs and eyewitness
      reports, allow changes in some drainage basins to be documented in fine detail
      over time periods ranging from a few days to several decades. The USA is rich in
      data sources that are freely available. Rates of bank erosion, meander migration,
      channel width, riparian vegetation and watershed land use and cover conditions
      can be assessed, which are especially valuable where there is controversy over
      the human contribution to erosion and deposition. Studies of Coon Creek and the
      southern Piedmont of the USA have yielded results that sometimes contradict
      established views.

PMID- 22474677
TI  - River sediments.
AB  - River history is reflected in the nature of the sediments carried and deposited
      over time. Using examples drawn from around the world, this account illustrates
      how river sediments have been used to reconstruct past environmental changes at a
      variety of scales in time and space. Problems arising from a patchy alluvial
      record and from influences external to the river basin can make interpretation
      difficult. The Nile is treated in some detail because its history is further
      complicated by tectonic, volcanic and climatic events in its headwaters and by
      enduring human impacts. It arose soon after 30 Ma. Since that time approximately
      100,000 km(3) of rock have been eroded from its Ethiopian sources and deposited
      in the eastern Mediterranean, with minor amounts of sediment laid down along its
      former flood plains in Egypt and Sudan. From these fragmentary alluvial remains,
      a detailed history of Nile floods and droughts has been reconstructed for the
      last 15 kyr, and, with less detail, for the past 150 kyr, which shows strong
      accordance with global fluctuations in the strength of the summer monsoon, which
      are in turn perhaps modulated by changes in solar insolation caused by changes in
      the Earth's orbit and by variations in solar irradiance.

PMID- 22474678
TI  - Modelling river history and evolution.
AB  - Over the last few decades, a suite of numerical models has been developed for
      studying river history and evolution that is almost as diverse as the subject of
      river history itself. A distinction can be made between landscape evolution
      models (LEMs), alluvial architecture models, meander models, cellular models and
      computational fluid dynamics models. Although these models share some
      similarities, there also are notable differences between them, which make them
      more or less suitable for simulating particular aspects of river history and
      evolution. LEMs embrace entire drainage basins at the price of detail; alluvial
      architecture models simulate sedimentary facies but oversimplify flow
      characteristics; and computational fluid dynamics models have to assume a fixed
      channel form. While all these models have helped us to predict erosion and
      depositional processes as well as fluvial landscape evolution, some areas of
      prediction are likely to remain limited and short-term owing to the often
      nonlinear response of fluvial systems. Nevertheless, progress in model
      algorithms, computing and field data capture will lead to greater integration
      between these approaches and thus the ability to interpret river history more
      comprehensively.

PMID- 22474679
TI  - The fluvial record of climate change.
AB  - Fluvial landforms and sediments can be used to reconstruct past hydrological
      conditions over different time scales once allowance has been made for tectonic,
      base-level and human complications. Field stratigraphic evidence is explored here
      at three time scales: the later Pleistocene, the Holocene, and the historical and
      instrumental period. New data from a range of field studies demonstrate that
      Croll-Milankovitch forcing, Dansgaard-Oeschger and Heinrich events, enhanced
      monsoon circulation, millennial- to centennial-scale climate variability within
      the Holocene (probably associated with solar forcing and deep ocean circulation)
      and flood-event variability in recent centuries can all be discerned in the
      fluvial record. Although very significant advances have been made in river system
      and climate change research in recent years, the potential of fluvial
      palaeohydrology has yet to be fully realized, to the detriment of climatology,
      public health, resource management and river engineering.

PMID- 22474680
TI  - River history and tectonics.
AB  - The analysis of crustal deformation by tectonic processes has gained much from
      the clues offered by drainage geometry and river behaviour, while the
      interpretation of channel patterns and sequences benefits from information on
      Earth movements before or during their development. The interplay between the two
      strands operates at many scales: themes which have already benefited from it
      include the possible role of mantle plumes in the breakup of Gondwana, the
      Cenozoic development of drainage systems in Africa and Australia, Himalayan
      uplift in response to erosion, alternating episodes of uplift and subsidence in
      the Mississippi delta, buckling of the Indian lithospheric plate, and changes in
      stream pattern and sinuosity along individual alluvial channels subject to
      localized deformation. Developments in remote sensing, isotopic dating and
      numerical modelling are starting to yield quantitative analyses of such effects,
      to the benefit of geodymamics as well as fluvial hydrology.

PMID- 22474681
TI  - The fluvial history of Mars.
AB  - River channels and valleys have been observed on several planetary bodies in
      addition to the Earth. Long sinuous valleys on Venus, our Moon and Jupiter's moon
      Io are clearly formed by lava, and branching valleys on Saturn's moon Titan may
      be forming today by rivers of methane. But by far the most dissected body in our
      Solar System apart from the Earth is Mars. Branching valleys that in plan
      resemble terrestrial river valleys are common throughout the most ancient
      landscapes preserved on the planet. Accompanying the valleys are the remains of
      other indicators of erosion and deposition, such as deltas, alluvial fans and
      lake beds. There is little reason to doubt that water was the erosive agent and
      that early in Mars' history, climatic conditions were very different from the
      present cold conditions and such that, at least episodically, water could flow
      across the surface. In addition to the branching valley networks, there are large
      flood features, termed outflow channels. These are similar to, but dwarf, the
      largest terrestrial flood channels. The consensus is that these channels were
      also cut by water although there are other possibilities. The outflow channels
      mostly postdate the valley networks, although most are still very ancient. They
      appear to have formed at a time when surface conditions were similar to those
      that prevail today. There is evidence that glacial activity has modified some of
      the water-worn valleys, particularly in the 30-50 degrees  latitude belts, and
      ice may also be implicated in the formation of geologically recent, seemingly
      water-worn gullies on steep slopes. Mars also has had a long volcanic history,
      and long, sinuous lava channels similar to those on the Moon and Venus are common
      on and around the large volcanoes. These will not, however, be discussed further;
      the emphasis here is on the effects of running water on the evolution of the
      surface.

PMID- 22474682
TI  - Indo-Gangetic river systems, monsoon and malaria.
AB  - The history of the Indo-Gangetic river systems from the late nineteenth to the
      early twentieth centuries can be reconstructed from the meticulous official
      records of the survey, meteorological and medical departments of the British
      Government of India. In contrast with the grand sweep of the geological evidence,
      these records indicate a complex narrative of floods, droughts and channel
      shifts. Similarly, the cumulative growth of the Ganges-Brahmaputra and Indus
      deltas was overprinted by the effects of the annual monsoon cycle on
      precipitation, temperature and winds. Malaria, the principal vector-borne disease
      of the Indian subcontinent, and the deadliest, displayed epidemiological types
      that ranged between the extremes of stable-endemic to unstable-epidemic as
      defined in the classic theory of equilibrium of George Macdonald. Variations in
      its transmission, incidence and prevalence were closely tied to the different
      deltaic environments of the Bengal and Indus basins and to the short-sightedness
      of many irrigation and related engineering schemes.

PMID- 22474683
TI  - Geomorphic histories for river and catchment management.
AB  - River and catchment management usually proceeds from the identification of an
      undesirable state (e.g. pollution, sedimentation, excessive water extraction,
      dams, invasion by exotic species) to a strategy for reaching a desirable state
      described as a target. Desirable states are usually determined from community
      values, economic assessments and ecosystem functions, or a combination of these.
      Where a catchment is highly disturbed, the target is usually not a natural state,
      as that cannot be achieved while maintaining human uses, and a history is needed
      to document the disturbance, understand its cause and define the 'existence
      space', that is, the range of natural states that have occurred in the past.
      Where a catchment is less disturbed, a former natural state could provide a
      target for management. But which of the many natural (equilibrium) states that
      have occurred in the past should be the target? The paper reviews what is known
      of the quantitative difference between pre- and post-disturbance states, searches
      for the presence or otherwise of equilibrium and comments on the utility of this
      information for catchment management. The focus is on erosion and sediment
      transport.

PMID- 22474684
TI  - Suspected ergotism causing lameness and distal limb necrosis in cattle.

PMID- 22474685
TI  - The benign form of multiple sclerosis. A study based on 241 cases seen within
      three years of onset and followed up until the tenth year or more of the disease.
      By Douglas McAlpine. From the Institute of Clinical Research, The Middlesex
      Hospital Medical School, London W1. Brain 1961: 84; 186-203.

PMID- 22474686
TI  - Towards optimizing wood development in bioenergy trees.
AB  - To secure a sustainable energy source for the future, we need to develop an
      alternative to fossil fuels. Cellulose-based biofuel production has great
      potential for development into a sustainable and renewable energy source. The
      thick secondary walls of xylem cells provide a natural source of cellulose. As a
      result of the extensive production of wood through cambial activity, massive
      amounts of xylem cells can be harvested from trees. How can we obtain a maximal
      cellulose biomass yield from these trees? Thus far, tree breeding has been very
      challenging because of the long generation time. Currently, new breeding
      possibilities are emerging through the development of high-throughput
      technologies in molecular genetics. What potential does our current knowledge on
      the regulation of cambial activity provide for the domestication of optimal
      bioenergy trees? We examine the hormonal and molecular regulation of wood
      development with the aim of identifying the key regulatory aspects. We describe
      traits, including stem morphology and xylem cell dimensions, that could be
      modified to enhance wood production. Finally, we discuss the potential of novel
      marker-assisted tree breeding technologies.

PMID- 22474687
TI  - Cellulose factories: advancing bioenergy production from forest trees.
AB  - Fast-growing, short-rotation forest trees, such as Populus and Eucalyptus,
      produce large amounts of cellulose-rich biomass that could be utilized for
      bioenergy and biopolymer production. Major obstacles need to be overcome before
      the deployment of these genera as energy crops, including the effective removal
      of lignin and the subsequent liberation of carbohydrate constituents from wood
      cell walls. However, significant opportunities exist to both select for and
      engineer the structure and interaction of cell wall biopolymers, which could
      afford a means to improve processing and product development. The molecular
      underpinnings and regulation of cell wall carbohydrate biosynthesis are rapidly
      being elucidated, and are providing tools to strategically develop and guide the
      targeted modification required to adapt forest trees for the emerging bioeconomy.
      Much insight has already been gained from the perturbation of individual genes
      and pathways, but it is not known to what extent the natural variation in the
      sequence and expression of these same genes underlies the inherent variation in
      wood properties of field-grown trees. The integration of data from next
      generation genomic technologies applied in natural and experimental populations
      will enable a systems genetics approach to study cell wall carbohydrate
      production in trees, and should advance the development of future woody bioenergy
      and biopolymer crops.

PMID- 22474690
TI  - Abstracts of the 67th Annual Scientific Convention and Meeting of the Society of
      Biological Psychiatry. May 3-5, 2012. Philadelphia, Pennsylvania, USA.

PMID- 22474688
TI  - Imaging of left main coronary artery thrombus with CT coronary angiography.

PMID- 22474691
TI  - Abstracts of the 46th Annual Scientific Meeting of the European Society for
      Clinical Investigation. Budapest, Hungary. March 22-24, 2012.

PMID- 22474692
TI  - Abstracts of the Society for Pediatric Radiology 55th Annual Meeting &
      Postgraduate Course. April 16-17, 2012. San Francisco, California, USA.

PMID- 22474693
TI  - Northern Ireland disease surveillance, October to December 2011.

PMID- 22474694
TI  - Abstracts of the 18th Annual Conference of the Society on Neuroimmune
      Pharmacology (SNIP). Honolulu, Hawaii, USA. April 25-28, 2012.

PMID- 22474695
TI  - Abstracts of the 15th ESSKA (European Society of Sports Traumatology, Knee
      Surgery and Arthroscopy) Congress. May 2-5, 2012. Geneva, Switzerland.

PMID- 22474696
TI  - [Lyrical tragedy].

PMID- 22474697
TI  - Can having fun protect you from obesity and its cancer risk?

PMID- 22474698
TI  - AWP leaves, AAC arrives; can it really do the job?

PMID- 22474699
TI  - Hospital administrators see bump in pay.

PMID- 22474700
TI  - Employers identify strategies to reduce pharmacy costs.

PMID- 22474701
TI  - States and plans adjust to ACA's reality.

PMID- 22474702
TI  - [Theory development in nursing in the 21st century].

PMID- 22474703
TI  - The new PSA report: understand the controversy.

PMID- 22474704
TI  - Learning while you sleep: dream or reality?

PMID- 22474705
TI  - Obesity in America: what's driving the epidemic?

PMID- 22474706
TI  - On call.  I do my best to exercise every day, either walking two miles in good
      weather or riding my exercise bike for 30 minutes on wet or cold days.  Should I
      keep going when I catch a cold, or would I be better off resting?

PMID- 22474707
TI  - On call.  When I awaken in the morning, I have terrible bad breath.  My breath
      seems okay during the rest of the day, but I worry about developing halitosis. 
      What causes bad breath?

PMID- 22474708
TI  - Eating disorders in adult women.  For some, aging may bring on--or rekindle--an
      eating disorder.

PMID- 22474709
TI  - Anxiety and gambling.  Anxiety can fuel a gambling problem.  A new book offers
      advice.

PMID- 22474710
TI  - Why coffee perks people up.  A large study suggests the caffeinated version may
      boost mood.

PMID- 22474711
TI  - Encouraging news about ADHD drugs and heart risk in adults.

PMID- 22474712
TI  - Medicaid analysis reveals trends in depression care.

PMID- 22474713
TI  - My father-in-law was just diagnosed with vascular dementia. The doctor said heart
      disease probably contributed to the problem. What exactly is vascular dementia,
      and how can I help my husband avoid the same fate?

PMID- 22474714
TI  - Progress towards global polio eradication - status of wild poliovirus circulation
      in Africa, 2011.

PMID- 22474715
TI  - Monthly report on dracunculiasis cases, January 2012.

PMID- 22474716
TI  - Xanthate based radical cascade toward multicomponent formation of
      pyrrolopyrimidines.
AB  - A short sequential synthesis of pyrrolidino- pyridines and pyrimidines
      illustrates the potential of combining Ugi-Smiles couplings with radical tin-free
      processes.

PMID- 22474717
TI  - Incidental 18F-FDG uptake in the thyroid in patients diagnosed with PET/CT for
      other malignancies.
AB  - BACKGROUND: The value of PET/CT imaging in diagnosis of different cancers has
      been widely described. PET/CT may contribute to visualization of additional
      findings that were not the indication to the study and did not refer to initial
      diagnosis. In a small number of PET/CT scans an incidentally found focal 18F-FDG
      uptake in the thyroid gland is found. The goal of the study was to estimate the
      prevalence and evaluate the clinical significance of incidental thyroid 18F-FDG
      uptake in a cohort of patients diagnosed for different malignancies. MATERIAL AND
      METHODS: 2478 PET/CT scans using 18F-FDG were performed in 1925 subjects for
      evaluation of different, non-thyroid malignancies. For PET/CT examination, a
      Discovery ST (General Electric) PET/CT scanner was used. Patients with focal 18F
      FDG activity were further evaluated by means of fine needle aspiration biopsy
      (FNAB). If cytological examination disclosed malignancy or suspicion of
      malignancy, thyroidectomy was performed. Both cytological and histopathological
      results were then analyzed. RESULTS: Focal increased 18F-FDG uptake was found in
      71 patients (3.7%), and cytological or histopathological results were evaluable
      in 20 of them. In general, 8 cases of thyroid cancer were found, which accounts
      for 40% probability of malignancy. The predominant histopathological diagnosis
      was papillary thyroid carcinoma (5 out of 8 cases). Additionally, in one case
      (5%) thyroid metastasis of lung cancer was detected. Diffused 18F-FDG activity in
      both thyroid lobes was observed in 120 subjects (6.2%)--in most cases chronic
      thyroiditis was confirmed. CONCLUSIONS: The probability of malignancy of focal
      thyroid incidentalomas in 18F-FDG PET/CT scans is rather high. Therefore,
      thorough evaluation of such lesions is highly recommended in each case. Most
      thyroid malignancies incidentally detected in PET/CT are papillary carcinomas.

PMID- 22474719
TI  - Bats increasingly seen  as vectors.

PMID- 22474718
TI  - NIH suspends new chimp  research grants.

PMID- 22474720
TI  - Families and their use of dental services.

PMID- 22474721
TI  - Electrodeposited biomimetic hydroxyapaptite coating, a potential evolution for
      dentin hypersensitivity.

PMID- 22474722
TI  - [Management of the pulmonary vein in the pericardium].

PMID- 22474723
TI  - The use of technology in providing dermatologic care to vulnerable populations.

PMID- 22474724
TI  - What is your diagnosis? Trichorhinophalangeal syndrome type I.

PMID- 22474725
TI  - Depigmentation therapy for vitiligo in patients with Fitzpatrick skin type VI.
AB  - Vitiligo is a depigmenting disorder characterized by the progressive loss of
      melanocytes. In cases of extensive vitiligo that is unresponsive to treatment and
      involves noticeable areas, such as the face and hands, total depigmentation is a
      clinical option. The choice to depigment is a difficult one for the patient given
      the irreversible nature of treatment and the psychosocial implications of skin
      color change. This issue can be particularly complex for black patients.
      Depigmentation has been practiced for decades and documented in the literature,
      but the practice in Fitzpatrick skin type VI is not well-documented. We present a
      case of depigmentation in a patient with Fitzpatrick skin type VI, as well as
      technical options for depigmentation, the clinical approach, patient preparation,
      and psychosocial issues involved with this treatment option.

PMID- 22474726
TI  - Congenital infantile fibrosarcoma: a clinical mimicker of hemangioma.
AB  - Congenital infantile fibrosarcoma (CIFS) is a rare pediatric soft tissue tumor;
      clinically, it presents as a highly vascular mass and may simulate a hemangioma.
      It usually occurs in the first year of life and has a relatively better prognosis
      compared to other aggressive spindle cell sarcomas of childhood. We report a
      patient with CIFS who presented with a nonspecific ulcerated mass lesion over the
      right shoulder region that was clinically diagnosed as a benign vascular lesion.
      Histology revealed a highly cellular tumor with closely packed fascicles of
      spindle cells. Immunohistochemically, the tumor cells expressed vimentin.

PMID- 22474727
TI  - Cutaneous Curvularia infection of the forearm.
AB  - Phaeohyphomycosis is the general term for infections caused by dematiaceous
      fungi. Although rare in humans, these infections are being reported at an
      increasing rate. Curvularia is a dematiaceous fungus that is ubiquitous among
      soil and vegetation in temperate areas and has only recently been revealed to
      cause human disease. Treatment guidelines have yet to be delineated due to the
      paucity of reported cases. We report the case of a 73-year-old man with chronic
      obstructive pulmonary disease, recent pneumonia caused by Actinomyces, and a
      localized plaque on his right lateral forearm extending to his medial arm caused
      by Curvularia species with complete resolution from itraconazole therapy.

PMID- 22474728
TI  - Intranasal tranexamic acid for the treatment of hereditary hemorrhagic
      telangiectasia: a case report and review of treatment options.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder.
      The disease has been formally characterized with epistaxis, cutaneous and mucosal
      telangiectases, a first-degree relative with HHT, and visceral lesions such as
      arteriovenous malformations (AVMs). Hereditary hemorrhagic telangiectasia has
      been underreported for many years. Wider recognition of this disorder in recent
      years has prompted researchers and physicians to recognize milder cases and focus
      on earlier treatment. This article highlights different treatments used to
      control epistaxis and screen for other complications associated with HHT.

PMID- 22474729
TI  - Primary cutaneous Nocardia brasiliensis infection isolated in an immunosuppressed
      patient: a case report.
AB  - Cutaneous nocardiosis is a rare infection that may manifest as a superficial skin
      lesion, lymphocutaneous infection, mycetoma, or diffuse cutaneous infection from
      a disseminated systemic infection. We report a case of a 65-year-old
      immunocompromised man with persistent primary cutaneous Nocardia brasiliensis
      infection following a motor vehicle collision. A high degree of suspicion is
      needed to diagnose Nocardia infection because of its resemblance to other
      bacterial infections. Nocardiosis should be included in the differential
      diagnosis of chronic cutaneous infections, especially when the response to
      antibiotics is inadequate or when the patient is immunocompromised. Because
      Nocardia may take several weeks to grow in standard bacterial culture media,
      laboratories should be notified of the suspicion so that culture plates are held
      for longer time periods. Long-term therapy, usually with sulfonamides, often is
      necessary.

PMID- 22474730
TI  - Herpes simplex virus type 2 of the palm as an AIDS-defining complex.
AB  - Herpes simplex virus type 2 (HHV-2) is one of the most common sexually
      transmitted diseases in the world. In the immunocompromised host, including
      patients with human immunodeficiency virus (HIV), herpes simplex virus is at high
      risk for reactivation. We present a woman with HIV and a large ulcer of the palm
      determined to be HHV-2. Not only was the location of her ulcer unusual, but her
      CD4 lymphocyte count continued to drop despite improvement of the palmar
      ulceration with treatment. As a result, her palmar HHV-2 ulcer became an AIDS
      defining complex.

PMID- 22474731
TI  - Poromatosis in pregnancy: a case of 8 eruptive poromas in the third trimester.
AB  - The poroid family of neoplasms includes hidroacanthoma simplex, eccrine poroma,
      dermal duct tumor, and poroid hidradenoma. These benign adnexal neoplasms are
      derived from the eccrine or apocrine sweat ducts or glands. Poroid neoplasms,
      including poromas, have been reported during pregnancy and have been hypothesized
      to be hormonally influenced. Poromatosis, the occurrence of multiple poromas,
      rarely has been reported in association with hidrotic ectodermal dysplasia, prior
      radiation therapy, and non-Hodgkin lymphoma occurring after chemotherapy. We
      report a case of eruptive poromatosis in pregnancy with 8 poromas occurring in
      the third trimester, further supporting the hypothesis of a hormonal association
      in the etiology of this neoplasm.

PMID- 22474732
TI  - Palmar telangiectases as a manifestation of Graves disease.
AB  - Telangiectases are lesions formed by persistent segmental dilatation of papillary
      plexus vessels of the skin that typically present as fine, bright, nonpulsatile
      red lines or netlike patterns. Palmar erythema commonly presents as symmetric,
      blanchable, slightly warm, nonscaling erythema, most frequently involving the
      thenar and hypothenar eminences of the palmar surface. Palmar telangiectases and
      palmar erythema both have primary cutaneous, systemic disease, neoplastic,
      infectious, and drug-induced etiologies. We describe a case of palmar
      telangiectases in a patient with Graves disease. We also describe the
      pathophysiology of palmar telangiectases and palmar erythema and present a
      literature review of their etiologies.

PMID- 22474733
TI  - Clobetasol propionate spray 0.05% for the treatment of moderate to severe plaque
      psoriasis.
AB  - Clobetasol propionate is a super-high potent class 1 topical corticosteroid
      available in several formulations, including a spray formulation that is approved
      for use up to 4 weeks in patients aged 18 years and older with moderate to severe
      plaque psoriasis. The efficacy and safety of clobetasol propionate spray 0.05%
      has been extensively evaluated in clinical trials in more than 2200 patients with
      moderate to severe plaque psoriasis. This article reviews the efficacy, safety,
      and tolerability of clobetasol propionate spray 0.05%. Clobetasol propionate
      spray 0.05% is a topical product with a documented efficacy and safety profile
      with good acceptability in patients with moderate to severe plaque psoriasis.

PMID- 22474734
TI  - The case for a specialist multidisciplinary valve clinic.
AB  - Valve disease is common and is increasing in prevalence as the population ages.
      The delivery of appropriate management is not always straightforward, and better
      ways of organizing care are required. Here, the argument is made for a specialist
      multidisciplinary valve clinic, while a description is provided of the authors'
      model clinic, which incorporates a specialist cardiologist in addition to
      sonographers and a nurse who carry out the surveillance services. The clinic is
      based at a cardiothoracic center and one district hospital, but could be
      generalized. Previous audits have shown that this model can reduce the number of
      patients seen by a cardiologist, thus improving the safety and quality of
      treatment compared to conventional clinics.

PMID- 22474735
TI  - Aortic valve re-replacement after Bentall procedure with a biological valved
      conduit in a sheep model.
AB  - BACKGROUND AND AIM OF THE STUDY: The Bentall procedure is the 'gold standard' for
      the repair of a combined pathology of ascending aorta and aortic valve. Because
      there is no need for long-term anticoagulation, biological-valved conduits have
      become increasingly popular; however, the possible need for reoperation due to
      valve degeneration is a major disadvantage. The aim of this animal-based study
      was to prove the feasibility of an isolated replacement of the aortic valve
      prosthesis six months after a previous implantation of a biological valved
      conduit (BioValsalva) in a sheep model. A total aortic root replacement, using
      the BioValsalva conduit, was performed in 10 juvenile sheep. After six months,
      the surviving sheep were reoperated on, and the stentless valve was replaced with
      a stented biological valve placed inside the previously implanted vascular
      conduit. RESULTS: Five animals survived the initial implantation of a BioValsalva
      conduit. During reoperation, the triple-layered vascular graft with
      polytetrafluoroethylene on the outside showed only slight adhesions with the
      surrounding tissue. The stentless valve was removed in one piece, after which a
      new stented valve was implanted inside the conduit. An X-radiographic examination
      of the explanted valve showed moderate calcification of the leaflet, and severe
      calcification of the aortic wall. CONCLUSION: The results of this animal study
      confirmed that a degenerated stentless biological valve inside the BioValsalva
      conduit could be replaced with a new valve, without having to remove the entire
      conduit.

PMID- 22474736
TI  - Regional variation in prosthesis choice for aortic valve replacement in older
      patients.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate regional
      practice patterns regarding aortic valve replacement (AVR) by comparing
      bioprosthetic versus mechanical valve usage in patients aged > or = 65 years, and
      to determine whether the choice of valve type for AVR in these patients varied by
      geographic region. METHODS: The details were acquired of all mechanical and
      bioprosthetic AVRs performed in patients aged > or = 65 years between 1999 and
      2006, as contained in the Florida State Inpatient Database. By using a small area
      analysis, the patients' zip codes were aggregated into hospital referral regions
      based on where they were most likely to receive AVR. The regional rates of both
      mechanical and bioprosthetic AVR were then determined. RESULTS: Of 23,925 AVRs
      performed during this period, 15,368 involved a bioprosthetic aortic valve and
      8,557 a mechanical aortic valve. Statewide, 64% of AVRs in these patients
      involved a bioprosthesis. Regional rates of mechanical AVRs varied widely, from
      10% to 81%. CONCLUSION: Substantial regional differences were identified in
      practice patterns for AVR in patients aged > or = 65 years. This suggested that
      provider preference, in addition to patient pathology, would often determine the
      type of valve implanted.

PMID- 22474737
TI  - Complementary assessment of aortic bioprosthetic dysfunction using cardiac
      magnetic resonance imaging and computed tomography.
AB  - The case is reported of a 28-year-old subject with a bioprosthesis (Shelhigh 31)
      in the aortic position, with symptoms of heart failure and possible prosthetic
      dysfunction. As the echocardiographic interrogation remained inconclusive, the
      patient underwent cardiovascular magnetic resonance (CMR) imaging, which revealed
      an impaired movement of the non-coronary cusp. In addition, computed tomography
      (CT) demonstrated severe calcification of the immobile prosthetic component.
      Hence, in selected patients, both CMR and CT can be used as complementary tools
      to evaluate the dysfunction and pathology of heart valve bioprostheses.

PMID- 22474738
TI  - Tezosentan inhibits uptake of proinflammatory endothelin-1 in stenotic aortic
      valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve stenosis (AS) is an actively
      regulated pathobiological process which has an inflammation origin, and manifests
      as an accumulation of lipids and, ultimately, calcification of the aortic valve
      tissue. Increased plasma levels of the proinflammatory factor endothelin-1 (ET-1)
      have been reported in AS. Moreover, increased tissue levels of ET-1 and its ET(A)
      receptor, which mediates the fibrotic and proliferative effects of ET-1, have
      been reported in stenotic aortic valves. The study aim was to determine whether
      endothelin receptor antagonism has an effect on the supposed receptor-mediated
      uptake of ET-1 to aortic valves when ET-1 may be involved in the pathogenesis of
      AS. METHODS: By using valve tissue explants in culture, it was determined whether
      the ET(A)-ET(B) receptor antagonist tezosentan was capable of reducing the uptake
      of 125I-labeled ET-1 to human aortic valves. Aortic valves were obtained from 16
      patients (11 males, five females; mean age 71 +/- 11.2 years) and from two donors
      without AS (as controls) at the time of aortic valve or aortic root surgery.
      Valve tissue samples were cultured in ET-1 (10 nmol/l), in the presence or
      absence of tezosentan (10 nmol/l). RESULTS: ET-1 uptake was found to be
      pronounced in the calcified areas of the valve, and tezosentan markedly reduced
      the receptor-mediated uptake of 125I-labeled ET-1. The inhibitory effect was most
      evident in the well-calcified part of the valve. The gene expression levels of
      the ET receptors ET(A) and ET(B) were unaltered in human aortic valves during a
      four-day exposure to the antagonist. CONCLUSION: The ability of the ET(A)-ET(B)
      receptor antagonist tezosentan to inhibit ET-1 uptake in valve tissue suggests
      that continuous ET antagonist therapy might serve as new strategy to slow down
      the pathophysiological processes of AS.

PMID- 22474739
TI  - Does gender affect the rates of abnormal exercise stress echocardiography in
      patients with asymptomatic severe aortic stenosis?
AB  - BACKGROUND AND AIM OF THE STUDY: Patient gender can affect not only the clinical
      manifestations of coronary artery disease (CAD) but also the clinician's
      interpretation of the symptoms and results of exercise stress tests for
      management decisions. This may be true also for aortic stenosis (AS), given its
      many shared features with CAD and similar symptom-based management. The study aim
      was to evaluate the effect of gender on the assessment of severe asymptomatic AS
      by exercise stress echocardiography (ESE). METHODS: A total of 160 patients (89
      males, 71 females) with severe asymptomatic AS and good left ventricular function
      underwent ESE for assessment of their clinical status. Of these patients, 133
      (83%) were followed up after echocardiography for a mean of 644 +/- 467 days. The
      findings and outcome were compared between males and females. RESULTS: No gender
      related differences were identified for mean age, baseline and peak exercise
      heart rates and blood pressures, aortic valve area, and prevalence of CAD. Female
      patients had a lower exercise capacity (shorter exercise time, lower exercise
      load), but there were no significant between-group differences in the exercise
      related parameters defining AS. In total, 38 women (24%) and 45 men (28%) were
      treated by aortic valve replacement (p = 0.2) within a similar time range from
      echocardiography (p = 0.6). CONCLUSION: Asymptomatic women with severe AS have
      similar rates of abnormal ESE as men, despite limitations in exercise capacity
      among women compared to men.

PMID- 22474740
TI  - New echocardiography-based classification of mitral valve pathology: relevance to
      surgical valve repair.
AB  - A new echocardiography-based classification of mitral valve pathology is
      proposed, the adoption of which may provide a uniform approach to the assessment
      of individual cases by the cardiologist, cardiac anesthesiologist, and surgeon.
      This type of approach may facilitate the planning and execution of valve repair
      techniques, with higher rates of success than are currently reported.

PMID- 22474741
TI  - Impact of hospital annual mitral procedural volume on mitral valve repair rates
      and mortality.
AB  - BACKGROUND AND AIM OF THE STUDY: The aim of this investigation was to examine the
      impact of hospital annual mitral volume on mitral valve (MV) repair rates and
      mortality. METHODS: The 2005-2008 Nationwide Inpatient Sample (NIS) database was
      searched to identify patients who had undergone either MV repair (ICD-9-CM code
      35.12) or MV replacement (ICD-9-CM codes 35.23 and 35.24). The hospitals were
      stratified into five categories based on the annual volume of all mitral
      procedures (< 10, 10-20, 21-40, 41-79, and > or = 80 cases/year). The
      relationship between hospital annual mitral procedure volume and MV repair rates,
      as well as hospital mortality for MV repair, was then examined for patients
      undergoing isolated MV surgery (excluding those aged < 30 years and those with
      congenital heart disease, concomitant coronary revascularization, ventricular
      aneurysm excision, heart transplant and other valvular interventions, except
      tricuspid). Chi-square tests of independence were used to test for differences
      between the mitral volume categories, and Cochran-Armitage tests to check for
      trends across the years. RESULTS: The sample included a total of 12,857 patients
      from 603 hospitals. Mitral repair rates increased as a function of hospital
      mitral volume, ranging from 34% for hospitals with < 10 mitral cases/year to 53%
      for hospitals with > or = 80 mitral cases/year. Follow up comparisons revealed
      that an annual mitral volume of > 40 cases/year was associated with a
      significantly higher rate of MV repair (p < 0.005). There was a significant trend
      of increasing MV repair rates over time for hospitals with annual mitral volumes
      of 20-40 and 41-79 cases/year (p = 0.0001). The MV repair mortality ranged from
      1.33% to 2.29%, and did not differ among hospitals as a function of the annual
      mitral volume (p = 0.2982). CONCLUSION: Mortality after MV repair was low, and
      independent of the hospital annual mitral volume. A hospital annual mitral volume
      of fewer than 40 cases per year was associated with a lower rate of MV repair.
      Addressing the factors responsible for this finding constitutes an important area
      for future improvement in the care of patients with MV disease.

PMID- 22474742
TI  - Geographic variation in procedure selection and hospital mortality in mitral
      valve surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: There is paucity of data relating to the
      geographic variation in mitral valve (MV) repair trends and outcomes of patients
      undergoing MV surgery. METHODS: Using the 2005-2008 Nationwide Inpatient Sample
      (NIS) Database, the four geographic regions of the US (Northeast, Midwest, South,
      and West) were compared with respect to baseline characteristics, mitral
      procedure selection, and hospital mortality of patients undergoing either MV
      repair (ICD-9CM code 35.12) or replacement (ICD-9-CM codes 35.23 and 35.24).
      RESULTS: Patient age was similar across regions. The Midwest had the highest
      proportion of whites, while patients in the South were the least affluent. The
      Northeast had the highest proportion of patients presenting non-electively. The
      West and Midwest had more women and patients with private insurance compared to
      the South, but the proportion of patients on Medicaid was similar across all
      regions. The Northeast and the South had a higher Charlson Comorbidity Index
      compared to the West. The overall repair rate was 47%; the Midwest had the
      highest rate (50%), and the South the lowest (42%) (p = NS). Following adjustment
      for baseline characteristics, hospital mortality was similar among regions for
      patients undergoing MV replacement. For the subset undergoing MV repair, hospital
      mortality was more than 2.5-fold higher in the South than in the Northeast (OR =
      2.88, 95% CI 1.45-5.71). CONCLUSION: MV repair is utilized in less than half of
      all mitral procedures nationwide. Repair rates and hospital mortality are
      comparable across all four regions in the US. Hospital mortality for isolated MV
      surgery is low. The higher adjusted mortality for patients undergoing MV repair
      in the South identifies an important area for future improvement in the care of
      patients with valvular heart disease.

PMID- 22474743
TI  - Risk of reoperation for mitral bioprosthesis dysfunction.
AB  - BACKGROUND AND AIM OF THE STUDY: Today, when a mitral valve replacement is
      required, more patients and surgeons choose a bioprosthesis. Yet, the rationale
      of this choice is unclear in patients in whom age represents a predicting factor
      for reoperation. The study aim was to define the risk factors for reoperation
      after mitral bioprosthesis failure. METHODS: A total of 282 consecutive patients
      (202 women, 80 men; mean age at surgery 61 years; range: 28-88 years) who
      underwent reoperation for mitral bioprosthesis failure between 1990 and 2006 was
      reviewed. Surgery was undertaken because of bioprosthesis degeneration (91%),
      prosthetic valve infective endocarditis (6%), paravalvular leak (2%), or other
      causes (1%). Emergency procedures were performed in 7% of cases. Associated
      procedures included tricuspid valve surgery in 16% of patients (tricuspid valve
      repair in 11%, tricuspid valve replacement in 5%) and coronary artery bypass
      graft in 5%. Almost one-fifth of patients (18%) had undergone more than one
      previous mitral valve replacement. RESULTS: The overall operative mortality was
      7.4% (n = 21). Factors identified (by multivariate analysis) as predictors of
      operative death included: presence of diabetes mellitus (odds ratio (OR) = 8.69,
      95% CI 2.55-29.61; p = 0.001), chronic obstructive pulmonary disease (OR = 9.01,
      95% CI 1.72-47.18; p = 0.009), NYHA class III/IV (OR 5.46, 95% CI 1.41-21.16; p =
      0.01), and pulmonary artery pressure > 60 mmHg (OR = 3.13, 95% CI 1.10-8.94; p =
      0.03). Associated procedures were not significant risk factors for mortality. New
      prostheses were mechanical in 68% of cases, and bioprostheses in 32%. CONCLUSION:
      One reoperation for mitral bioprosthesis dysfunction is acceptable if the patient
      can be expected to survive to reoperation while free from comorbidities and the
      severe effects of mitral disease. The application of strict selective criteria to
      recipients at the first valve replacement, combined with a close follow up, may
      allow this goal to be achieved.

PMID- 22474744
TI  - Early surgery for asymptomatic mitral regurgitation: importance of atrial
      fibrillation.
AB  - BACKGROUND AND AIM OF THE STUDY: It remains controversial whether early mitral
      valve (MV) repair should be performed for severe degenerative mitral
      regurgitation (MR) without symptoms, left ventricular (LV) dilatation or
      dysfunction, atrial fibrillation (AF) or pulmonary artery hypertension (PH), even
      at experienced surgical centers. The study aim was to reconsider the optimal
      timing of intervention for asymptomatic patients with severe degenerative MR at
      experienced surgical centers. METHODS: Clinical outcomes were reviewed
      retrospectively for 298 consecutive asymptomatic patients (mean age 57 +/- 12
      years) who underwent MV surgery for degenerative MR. The patients were allocated
      to two groups based on the following comorbid conditions: LVEF < or = 60%, LV end
      systolic dimension 40 mm, AF, and PH. Group A comprised 122 patients with none of
      these conditions, while group B comprised 176 patients with any one of the
      conditions. The clinical outcomes were compared between the two groups at a mean
      of 7.0 +/- 4.5 years after surgery. RESULTS: MV repair had been attempted in all
      patients, with a success rate of 100%. At 10 years, survival among group B
      patients was poorer than in group A (93% and 81%, respectively; p = 0.02), and
      there was a lower freedom from valve-related events (89% and 71%, respectively; p
      < 0.01). The independent predictors of valve-related events were preoperative AF
      (hazard ratio 3.34; p < 0.001) and age > 60 years (hazard ratio 2.50; p < 0.01).
      CONCLUSION: Early MV repair is a reasonable option in asymptomatic patients,
      while preoperative AF may be a more appropriate predictor of an adverse outcome
      than LV function, as is currently recommended.

PMID- 22474745
TI  - Assessment of a novel stentless mitral valve using a pulsatile mitral valve
      simulator.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to develop a novel stentless
      mitral valve (SMV) and to evaluate its performance, using an original pulsatile
      simulator developed specifically to analyze the hydrodynamic function of the
      mitral valve. METHODS: The SMV developed at the authors' institution consists of
      two major components: a large anterior leaflet with commissures, and a small
      posterior leaflet. The valve is formed by suturing the leaflets (made from bovine
      pericardium) to a flexible (Duran) ring. The SMV, constructed with a 27 mm
      flexible ring, was installed into the mitral valve simulator, after which the
      four papillary flaps of the two leaflets were sutured to artificial papillary
      muscles. The artificial ventricle was driven pneumatically at a pulse rate of 70
      beats/min, with a systolic fraction of 35%. The mean flow, aortic pressure, and
      atrial pressure were adjusted to 4.5 1/min, 120/80 mmHg, and 10 mmHg,
      respectively. A 27 mm mechanical valve (MEV; St. Jude Medical Inc.) was employed
      as a control. The hydrodynamic performance of the SMV and MEV were investigated
      and compared. An echo-Doppler study was also performed. RESULTS: The waveforms of
      the SMV and MEV showed a similar pattern. The mean transvalvular flow was 4.7 +/-
      0.4 1/min for the SMV, and 3.55 +/- 0.13 1/min for the MEV (p < 0.001). Mitral
      regurgitation was 5.07 +/- 1.15 and 3.78 +/- 0.35 ml/beat, respectively (p <
      0.05). Echocardiographic data indicated that the regurgitant jet towards the left
      atrial model was none or trivial for the SMV, and trivial for the MEV.
      CONCLUSION: Within the environment of the mitral valve simulator, the novel SMV
      prepared from bovine pericardium demonstrated excellent performance
      characteristics, and may represent a potential future alternative for
      bioprosthetic stented mitral valves.

PMID- 22474746
TI  - Patterns of anticoagulation following bioprosthetic valve implantation:
      observations from ANSWER.

PMID- 22474748
TI  - Twenty years' single-center experience with mechanical heart valves: a critical
      review of anticoagulation policy.
AB  - BACKGROUND AND AIM OF THE STUDY: Since January 1990, a variety of mechanical
      valves (St. Jude Medical, CarboMedics, ATS Medical) have been implanted routinely
      at the authors' institution. The study aim was to analyze, retrospectively, the
      20-year clinical results of those mechanical valves, and to challenge the
      anticoagulation policy employed over the years. METHODS: Between January 1990 and
      December 2008, a total of 2,108 mechanical valves was inserted into 1,887
      consecutive patients (1,346 aortic, 725 mitral, 27 tricuspid, 10 pulmonary). The
      mean age of the patients was 63 +/- 13.2 years, and the majority (61%) were
      males. Preoperatively, 71% the patients were in NYHA class > or = III (average
      3.01). The most frequent comorbidities included: atrial fibrillation (n = 594),
      coronary disease (n = 567) and diabetes (n = 398). The follow up (99% complete)
      totaled 13,721 patient-years (pt-yr), and ranged from 12 to 241 months (average
      84 months). RESULTS: In-hospital mortality was 5.2% (n = 98, 14 valve-related).
      Of the 629 late deaths, the majority were cardiac (n = 276). Survival (Kaplan
      Meier estimation) was significantly better for aortic valve patients compared to
      mitral or multiple valve replacement (Mantel-Cox, p < 0.0001). The overall
      linearized incidences (as %/pt-yr) were: valve thrombosis 0.31, thromboembolism
      1.08, and bleeding 0.91. However, as repeated events occurred in several
      patients, the hazard function was not constant. Multivariate analysis (Cox
      regression model) showed age > 70 years (p < 0.0001), NYHA class > or = III (p <
      0.0001), non-sinus rhythm (p = 0.001), concomitant coronary artery bypass
      grafting (p = 0.008) and higher International Normalized Ratio (INR) values (p =
      0.013) as significant risk factors for death, with a trend for redo operations (p
      = 0.052). Multivariate analysis found variable INR, non-sinus rhythm and NYHA
      class > II as significant risk factors for thromboembolism, while long-acting
      coumadin and NYHA class > II were significant risk factors for bleeding.
      CONCLUSION: This 20-year experience demonstrated excellent clinical outcomes for
      patients with mechanical prostheses, with no valve structural failure and an
      acceptable incidence of adverse events. INR values between 2-2.5 for aortic valve
      patients, and 3-3.5 for mitral valve patients, yielded the fewest major adverse
      events.

PMID- 22474747
TI  - Patterns of anticoagulation following bioprosthetic valve implantation:
      observations from ANSWER.
AB  - BACKGROUND AND AIM OF THE STUDY: The American College of Cardiology/American
      Heart Association (ACC/AHA) guidelines recommend a three-month administration of
      warfarin following bioprosthetic valve replacement (BVR). However, strong
      evidence supporting this recommendation is lacking, making process variation
      likely. METHODS: In the ANSWER Registry, a total of 386 patients who had received
      either Epic or Biocor BVRs between May 2007 and August 2008 at 40 centers was
      enrolled. Patterns of discharge anticoagulation and outpatient International
      Normalized Ratio (INR) values were collected. Mortality, embolic, and bleeding
      events were assessed up to six months after BVR. RESULTS: The median patient age
      was 74 years (interquartile range (IQR): 67-80 years), 39% of patients were
      female, and 65% were classified as a high thromboembolic risk. Warfarin was
      prescribed in 38% of all BVR patients, and in 49% of those at high risk of
      thromboembolism. The median time to therapeutic INR was nine days (IQR: 1 to 18
      days), and 20% of patients failed to reach therapeutic levels. Among those
      patients achieving a therapeutic INR, 78% and 57% respectively had at least one
      subtherapeutic or supratherapeutic INR during the subsequent follow up to three
      months. During the follow up, patients treated with warfarin had similar rates of
      embolic events (2.8% versus 3.1%, p = 0.884), but a substantially higher
      incidence of bleeding than those not treated with warfarin (12% versus 3%, p =
      0.0012). Among patients who were anticoagulated, those with supratherapeutic INR
      values had a seven-fold higher risk for overt bleeding events (26% versus 3%).
      CONCLUSION: Anticoagulation strategies after BVR are highly variable. In this
      population, challenges in achieving and maintaining therapeutic warfarin
      anticoagulation are common, and are associated with an increased risk of
      bleeding. Further studies are required to clarify the optimal post-BVR
      anticoagulation strategy.

PMID- 22474749
TI  - Diastolic properties of the Sorin Solo, ATS 3F, Edwards Prima Plus and Medtronic
      Freestyle stentless valves: an independent in-vitro comparison.
AB  - BACKGROUND AND AIM OF THE STUDY: Currently, little is known of the diastolic
      properties of stentless valves that affect stress and strain on leaflets and,
      hence, their durability. In a pressurized aortic root model, a series of in-vitro
      tests was conducted to determine how stentless valves behave in diastole, and how
      they adapt to different annulus-to-sinotubular junction (STJ) ratios. METHODS:
      Sixteen 25 mm stentless aortic valves (four each of the Sorin Solo, ATS 3F,
      Edwards Prima Plus and Medtronic FreeStyle) were sutured into a 32 mm Valsalva
      graft, suspending the commissures into the expandable region (42 mm). The
      neoaortic root was pressurized and the size of the STJ progressively reduced by
      wrapping the neocommissural ridge with Dacron rings. Endoscopic views and
      ultrasound imaging were used to observe the geometry of the leaflets,
      regurgitation, and the height and level of leaflet coaptation at different
      annulus-to-STJ ratios. RESULTS: Pericardial prostheses built to mimic a cylinder
      (ATS 3F and Sorin Solo) showed the greatest tolerance to STJ dilatation and a
      larger coaptation surface, but also a tendency to roll in on themselves in an
      italic S-shape if oversized. Valves built to mimic native aortic leaflets
      (porcine Prima Plus and Medtronic Freestyle) showed a reduced tolerance to STJ
      dilatation, resulting in regurgitation and a smaller coaptation surface, but also
      a reduced tendency to roll if oversized. CONCLUSION: Despite similar systolic
      performances, stentless prostheses behave differently during diastole. The 3F and
      Solo valves benefit from a better tolerance to STJ dilatation, while the Prima
      Plus and Freestyle benefit from a more stable shape of closure under conditions
      of oversizing.

PMID- 22474750
TI  - Predicting the occurrence of valve prosthesis-patient mismatch: the need for more
      data.

PMID- 22474751
TI  - Manufacturer-provided effective orifice area index charts and the prevention of
      prosthesis-patient mismatch.
AB  - Prosthesis-patient mismatch (PPM) occurs when an implanted prosthesis is too
      small relative to the patient's body surface area (BSA). However, mismatch can
      often be prevented by indexing the expected effective orifice area (EOA) of a
      prosthesis to the patient's BSA and then selecting the largest implantable
      prosthesis to avoid mismatch. Previously, prosthesis manufacturers have attempted
      to simplify this process by providing charts that include the expected EOA for
      their prosthesis, already indexed into an array of BSA values. One caveat with
      these charts is that the expected EOA data must truly be reliable, or the charts
      will misguide the implanting surgeon. Manufacturer-provided charts could be
      improved by standardizing the EOA data, with one potential source being the
      hemodynamic data submitted to the United States Food and Drug Administration.
      This review discusses PPM, manufacturer-provided EOA charts, and the regulation
      of EOA data.

PMID- 22474752
TI  - Carpentier-Edwards Magna ease versus Magna valves: a comparison of in-vitro valve
      hydrodynamic performance.
AB  - BACKGROUND AND AIM OF THE STUDY: Previous studies have shown that the Carpentier
      Edwards Magna (CEM) valve is an excellent bioprosthesis in terms of its systolic
      performance; indeed, it has been described as 'a stented valve with stentless
      performance'. However, valve performance is not only a matter of gradients; it is
      also necessary to evaluate the diastolic-phase performance. Previous in-vitro
      studies have shown that the CEM has an excessive total regurgitant volume. Hence,
      the study aim was to compare the hydrodynamics of the CEM, with the newly evolved
      version of this valve, the CEM Ease (CEME). METHODS: The CEM and CEME valves
      (both 21 mm) were tested in the aortic chamber (23 mm diameter) of the Sheffield
      pulse duplicator. The tests were carried out at increasing pulse rates (PR; 70
      100 beats/min), and at each pulse rate the valve was tested at different stroke
      volumes (SVs; 45-65 ml). The forward-flow pressure drop, closing leakage volumes
      and effective orifice area (EOA) were recorded. RESULTS: The CEM and CEME valves
      showed a comparable systolic-phase performance, there being no significant
      differences in terms of transvalvular gradient, EOA and stroke work loss,
      regardless of the PR and SV. In fact, the new CEME exhibited a significantly
      improved diastolic performance, with the total regurgitant volume being
      significantly lower, due especially to a reduced leakage volume and, to a lesser
      extent, a reduced closing volume. CONCLUSION: The study results indicated that
      the new CEME valve would maintain the excellent systolic performance of the
      previous CEM model, but with a significantly improved diastolic performance.

PMID- 22474753
TI  - Infective endocarditis in a tertiary referral hospital: long-term follow up.
AB  - BACKGROUND AND AIM OF THE STUDY: Infective endocarditis (IE) is associated with
      significant mortality and morbidity. The aim of the present study was to assess
      the long-term survival of patients with IE, and to assess objectively the
      mortality in these patients by comparing their survival with that of an age- and
      gender-matched sample of the general population. METHODS: A retrospective
      observational cohort study of adults with IE, as determined by the modified Duke
      criteria, was admitted to a tertiary referral center between January 1998 and
      December 2007. Cumulative survival was analyzed using the Kaplan-Meier method.
      The log-rank test was used to compare the different groups, and multivariate Cox
      proportional hazards regression analyses were carried out to identify predictors
      of long-term, all-cause mortality. RESULTS: A total of 191 consecutive patients
      with IE was evaluated (176 left-sided, 15 right-sided). Cardiac surgery was
      performed in 72% of cases, and the median follow up was 6.3 years. The cumulative
      long-term survival was 59% after 10 years of follow up, the main causes of death
      being congestive heart failure (28%) and different type of malignancy (17%). Age-
      and gender-matched survival in the general population was 98%, 92%, and 80% after
      follow up periods of one, five, and ten years, respectively. The main predictor
      of long-term mortality was cancer, while surgery had a positive effect on long
      term survival. CONCLUSION: Despite diagnostic and therapeutic advances, IE is
      associated with a high long-term mortality. Compared to the general Dutch
      population, the survival of patients with IE was significantly lower. Even in the
      event of IE being cured, the survival of these patients may be diminished
      compared to that of the general population. Hence, a careful follow up of these
      patients is warranted.

PMID- 22474754
TI  - Heart valve engineering: decellularized aortic homograft seeded with human
      cardiac stromal cells.
AB  - BACKGROUND AND AIM OF THE STUDY: The adult human heart contains a cardiac
      mesenchymal stromal cell (CStC) population with residual cardiovascular
      plasticity. The study aim was to investigate the ability of CStCs to populate
      decellularized aortic homograft leaflets, without mechanical stimulation.
      METHODS: The ability of CStCs to acquire valve endothelial and interstitial cell
      phenotypes was tested using in vitro assays. First, trypsin-decellularized aortic
      leaflets were seeded with CStCs under static conditions; tissue section analyses
      were then performed before and after decellularization, and at 10, 20, and 30
      days after reseeding. RESULTS: Following in vitro treatment, the CStCs
      differentiated along the endothelial lineage, as shown by their capacity to
      uptake acetylated low-density lipoprotein and to secrete the pro-angiogenic
      factor, vascular endothelial growth factor. After seeding, CStCs were able to
      adhere to the leaflet surface, rescuing up to the 90% of the original cell
      density and expressing the mature endothelial marker, von Willebrandt factor. The
      CStC supernatants were also positive for matrix metalloprotease-2 (MMP-2), which
      confirmed the ability of these cells to penetrate within the leaflet structure;
      this also suggested that CStCs, once engrafted, would contribute to the
      extracellular matrix turnover. Accordingly, although at a lower efficiency, CStC
      repopulation was also evident in the inner portions of the leaflet. CONCLUSION:
      Seeded CStCs were able to reconstitute, without mechanical stimulation, an
      endothelial-like layer and to partially infiltrate decellularized homograft
      leaflets. Hence, CStCs appear to be a potentially useful cell type for engineered
      heart valves.

PMID- 22474755
TI  - Left coronary ostium isolation and aortic valve dysplasia in a young boy: a case
      report.
AB  - Congenital anomalies of the aortic valve represent a common malformation.
      Infrequently, a dysplastic aortic valve leaflet causes a severe coronary artery
      anomaly. Here, the case is reported of a malformed aortic valve in which the left
      rudimentary cusp occluded the left coronary ostium. At surgery the left coronary
      ostium was completely freed from the anomalous valvular tissue, a Konno operation
      was performed, and a 19 mm St. Jude Medical mechanical prosthesis was implanted.
      To date, very few reports have made of this rare malformation; moreover, to the
      present authors' knowledge this is the only case to have been treated.

PMID- 22474756
TI  - Valve leaflet reconstruction in pediatrics with extracellular matrix patch.

PMID- 22474757
TI  - First documented surgical case of human aortic valve endocarditis caused by
      Pasteurella haemolytica.

PMID- 22474758
TI  - Events in aortic stenosis patients with diabetes.

PMID- 22474759
TI  - The effect of fear in the periphery in binocular rivalry.
AB  - The perceived dominance of percepts within a rival pair of images can be
      influenced by emotional content, with emotional images dominating over neutral
      images. We investigated this effect in the periphery. Rival gratings and (fearful
      or neutral) face/house pairs were viewed centrally and with the near edge
      positioned 1 degrees and 4 degrees from the fixation. Both fearful and neutral
      faces were perceived as dominant for significantly longer than houses, with
      fearful faces dominating for significantly longer than neutral faces at all three
      eccentricities. There was no difference between dominances at 1 degrees and 4
      degrees eccentricity, and there was no difference in the dominance of the
      gratings at any eccentricity. Our findings show that face stimuli, and in
      particular fearful faces, continue to dominate perception in binocular rivalry
      even when viewed in the periphery.

PMID- 22474760
TI  - The effect of language on visual contrast sensitivity.
AB  - Embodied cognition and perceptual symbol theories assume that higher cognition
      interacts with and is grounded in perception and action. Recent experiments have
      shown that language processing interacts with perceptual processing in various
      ways, indicating that linguistic representations have a strong perceptual
      character. In the present study, we have used signal detection theory to
      investigate whether the comprehension of written sentences, implying either
      horizontal or vertical orientation, could improve the participants' visual
      sensitivity for discriminating between horizontal or vertical square-wave
      gratings and noise. We tested this prediction by conducting one main and one
      follow-up experiment. Our results indicate that language can, indeed, affect
      perception at such a low level of the visual process and thus provide further
      support for the embodied theories of cognition.

PMID- 22474761
TI  - Stereopsis loses dominance over relative size as target separation increases.
AB  - Binocular disparity produces less stereoscopic depth if the targets are separated
      by several degrees. It is thus possible that separation decreases the influence
      of stereopsis as a relative depth cue. Here, four experiments tested the strength
      of disparity in determining the direction of relative depth in the face of
      strongly conflicting relative size for a range of target separations. Under
      conditions of natural fixation-permitting sequential stereopsis-disparity
      dominated completely at small separations (0.42 degrees) but gradually gave way
      to relative size domination at large separations. However, when brief
      presentations prevented changes in fixation, disparity completely dominated at a
      separation of 0.5 degrees while relative size mostly dominated by 0.75 degrees -
      1 degrees of separation. By varying target separation at different retinal
      eccentricities, we showed that separation per se was the critical factor in the
      dominance switch. Stereoacuity as a function of target separation for the same
      observers did not predict the switch from disparity to relative size.
      Stereoscopic dominance was found for the same small separations that are immune
      to stereoscopic reversals (Gillam, 1993 Perception 22 1025-1036). Our results
      suggest that relative disparity has a compulsory influence on perceived depth at
      small separations, suggesting a different mechanism from the one operating at
      larger separations.

PMID- 22474762
TI  - Mapping the perceptual structure of rectangles through goodness-of-fit ratings.
AB  - Three experiments were carried out to investigate the internal structure of a
      rectangular frame to test Arnheim's (1974 Art and Visual Perception, 1988 The
      Power of the Center) proposals about its 'structural skeleton'. Observers made
      subjective ratings of how well a small probe circle fit within a rectangle at
      different interior positions. In experiment 1, ratings of 77 locations were
      highest in the center, decreased with distance from the center, greatly elevated
      along vertical and horizontal symmetry axes, and somewhat elevated along the
      local symmetry axes. A linear regression model with six symmetry-related factors
      accounted for 95% of the variance. In experiment 2 we measured perceived fit
      along local symmetry axes versus global diagonals near the corners to determine
      which factor was relevant. 2AFC probabilities were elevated only along the local
      symmetry axes and were higher when the probe was closer to the vertex. In
      experiment 3 we examined the effect of dividing a rectangular frame into two
      rectangular 'subframes' using an additional line. The results show that the
      primary determinant of good fit is the position of the target circle within the
      local subframes. In general, the results are consistent with Arnheim's proposals
      about the internal structure of a rectangular frame, but an alternative
      interpretation is offered in terms of the Gestalt concept of figural goodness.

PMID- 22474763
TI  - Skill level and graphical detail shape perceptual judgments in tennis.
AB  - Reducing the representation of human actions from normal video to biological
      motion animation in perceptual tasks means removing a number of visual features
      from the scenery, thereby eliminating potentially useful information for
      successfully performing the task. To determine the impact of selected visual
      features on perceptual judgments in tennis, we invited skilled players and
      novices to predict baseline shot direction under four different display
      conditions (PL: point-light display; PL_TC: PL plus an animated tennis court;
      NV_NB: normal video without ball; NV: normal video). Skilled players clearly
      outperformed novices and prediction performance increased with more realistic
      display content. Both groups were similarly affected by display conditions and
      across groups significant differences between conditions were only found for PL
      vs NV, and PL_TC vs NV, respectively. Application of signal detection theory on
      response data revealed that, unlike novices, skilled players showed a bias
      towards preferentially expecting cross-court shots and this bias increased with
      enhancement in graphical detail. Results confirm previous research in that
      biological motion appears to provide the minimal essential information necessary
      for correctly predicting an opponent's intent, particularly in skilled players.
      In addition, findings indicate that a combination of player and scenery-related
      visual information is likely to facilitate visual anticipation; however, such
      information seems to impact skilled players' and novices' response behaviour
      differently.

PMID- 22474764
TI  - Visual influences on interactive speech alignment.
AB  - Speech alignment describes the unconscious tendency to produce speech that shares
      characteristics with perceived speech (eg Goldinger, 1998 Psychological Review
      105 251-279). In the present study we evaluated whether seeing a talker enhances
      alignment over just hearing a talker. Pairs of participants performed an
      interactive search task which required them to repeatedly utter a series of
      keywords. Half of the pairs performed the task while hearing each other, while
      the other half could see and hear each other. Alignment was assessed by naive
      judges rating the similarity of interlocutors' keywords recorded before, during,
      and after the interactive task. Results showed that interlocutors aligned more
      when able to see one another suggesting that visual information enhances speech
      alignment.

PMID- 22474765
TI  - Interactions between intrinsic principles of similarity and proximity and
      extrinsic principle of common region in visual perception.
AB  - The interactions between intrinsic grouping principles (by proximity or by
      similarity in shape or luminance) and extrinsic grouping by common region were
      examined by presenting both principles acting alone or conjoined with another
      principle in visual patterns. The procedure used in our study closely mirrored
      that of Quinlan and Wilton (1998 Perception 27 417-430). However, in the present
      experiment, the intrinsic and extrinsic grouping principles involved had similar
      relative salience in order to avoid their possible effects on interactions. The
      results showed that the grouping effect of conjoined cooperating principles was
      greater than that of either principle acting alone, and the grouping effect of
      conjoined competing principles was lower than that of either principle operating
      alone. Compatibility of data with additive effects of grouping principles has
      been examined.

PMID- 22474766
TI  - Configural face processing: a meta-analytic survey.
AB  - In the field of face processing, the configural hypothesis is defended by many
      researchers. It is often claimed that this thesis is robustly supported by a
      large number of experiments exploring the face-inversion effect, the composite
      face effect, the face superiority effect, and the negative face effect. However,
      this claim is generally based on a rudimentary and approximate vote-counting
      approach. In this paper, I use meta-analyses to examine the relevant literature
      in more depth. The analysis supports the vote-counting argument.

PMID- 22474767
TI  - Perception of surface glossiness by infants aged 5 to 8 months.
AB  - We examined glossiness perception in infants using a preferential looking
      paradigm. In experiment 1, the images of two doll-shaped objects with matte and
      glossy surfaces were presented to infants aged 5 to 6 and 7 to 8 months. The
      results showed that the 7 to 8 month olds, but not the 5 to 6 month olds, looked
      significantly longer at the glossy object than at the matte object. In experiment
      2, we additionally employed an object that was matte and covered with textures of
      white paint splashes, whose luminance histogram was almost identical to that of
      the glossy object. The results showed that the 7 to 8 month old infants could
      discriminate between the glossy object and the textured object even though both
      had similar luminance histograms. Qualitatively similar results were obtained for
      simple spheres that did not contain facial features. Therefore, the results of
      experiments 1 and 2 were not due to differences in the visibility of the dolls'
      facial features. These findings suggest that 7 to 8 month old infants perceive
      difference between glossy objects and matte objects on the basis of surface
      representations.

PMID- 22474768
TI  - The role of mask coherence in motion-induced blindness.
AB  - Motion-induced blindness (MIB) is the perceived disappearance of a salient target
      when surrounded by a moving mask. Much research has focused on the role of target
      characteristics on perceived disappearance by a coherently moving mask. However,
      we asked a different question: mainly, are there certain characteristics about
      the mask that can impact disappearance? To address this, we behaviorally tested
      whether MIB is enhanced or reduced by the property of common fate. In experiments
      1, 2, and 3, we systematically manipulated the motion coherence of the mask and
      measured the amount of target disappearance. Results showed that, as mask
      coherence increased, perceived target disappearance decreased. This pattern was
      unaffected by the lifetime of the moving dots, the dot density of the motion
      stimulus, or the target eccentricity. In experiment 4, we investigated whether
      the number of motion directions contained in an incoherent mask could account for
      our findings. Using masks containing 1, 3, and 5 motion directions, we found that
      disappearance did not increase proportionally to the number of motion directions.
      We discuss our findings in line with current proposed mechanisms of MIB.

PMID- 22474769
TI  - The importance of CPD.

PMID- 22474770
TI  - Plus ca change.

PMID- 22474771
TI  - Theatre staffing.

PMID- 22474772
TI  - Operating department staffing...where will it end?

PMID- 22474773
TI  - Laser safety: practical measures and latest legislative requirements.
AB  - Lasers are used for a wide range of applications in operating departments and all
      persons working in a laser environment are required to understand the safety
      issues involved. This article details the various hazards associated with laser
      use and the management structure, procedures and control measures that should be
      implemented to ensure the health and safety of staff and patients.
      Recommendations are made in the context of the latest guidance and legislative
      requirements with reference to common issues that may arise in the workplace.

PMID- 22474774
TI  - Bone cement: perioperative issues, orthopaedic applications and future
      developments.
AB  - Bone cement has been increasingly used in orthopaedic surgery over the last 50
      years. Since Sir John Charnley pioneered the use of polymethylmethacrylate cement
      in total hip replacements, there have been developments in cementing techniques
      and an expansion in the number of orthopaedic procedures that use cement. This
      review covers the perioperative issues surrounding bone cement including storage,
      cementing techniques and complications. It also discusses specific orthopaedic
      applications of bone cement and future developments.

PMID- 22474775
TI  - Airway management: from pre-assessment to intubation. A student ODP's
      perspective.
AB  - Airway management is a fundamental skill in the implementation and maintenance of
      a general anaesthetic. An anaesthetised patient does not have full control over
      their airway, and without management a partial obstruction or other more serious
      complication may occur (Griffiths 1999). There are many ways to reduce the risk
      of complications occurring in the anaesthetic process. These methods can be
      subdivided into two main categories: prior preparation (Chethan & Hughes 2008)
      and pre-assessment (Neacsu 2002).

PMID- 22474776
TI  - Anaesthesia and the autistic child.
AB  - There appears to be little literature in paediatric anaesthetic practice relevant
      to children suffering with autism (Rainey & Van der Walt 1998). Recent findings
      suggest a need for rigorous study of the potential problems that autistic
      children may have when undergoing an anaesthetic (Kirz 2007). Some healthcare
      professionals do not have the knowledge or professional guidance to be able to
      identify these children (DH 2001, Disability Rights Commission 2006, DH 2008a, b,
      2009, Rankin 2009).

PMID- 22474777
TI  - Perioperative transoesophageal echocardiography.
AB  - New technologies are being introduced every day in the perioperative setting and
      perioperative practitioners will need to become increasingly familiar with
      transoesophageal echocardiography (TOE). TOE is used as a diagnostic tool during
      cardiac surgery in the operating theatre to direct the surgical procedure and to
      detect acute complications. TOE is also used to monitor cardiac function in
      patients undergoing non-cardiac surgery and in the intensive care unit (ICU)
      (Figure 1). The use of TOE is increasing in the cardiac catheterisation
      laboratory for percutaneous transcatheter procedures such as patent foramen ovale
      (PFO) closure, atrial septal defect (ASD) closure, aortic and mitral
      valvuloplasty, aortic valve implantation and mitral valve repair. Since the
      oesophagus is located directly behind the heart, TOE provides better image
      quality than transthoracic imaging for the assessment of posterior cardiac
      structures such as the mitral valve, left atrium and pulmonary veins.

PMID- 22474778
TI  - [BMI and waist circumference are too narrow measures].

PMID- 22474779
TI  - [New European guidelines for myocardial infarction without ST-segment elevation.
      Quicker diagnosis saves money--demands for angiography also during weekends costs
      more].

PMID- 22474780
TI  - [Bilingualism best if young people with cochlear implants get to choose.
      Interview study on the experience of participation in social interplay].

PMID- 22474781
TI  - [The medical profession, a profession with less and less support and influence. A
      questionnaire study the occupational environment of Swedish physicians in 1992
      and 2010].

PMID- 22474782
TI  - [Birth-Hogg-Dube syndrome--a neglected condition that increases the risk of
      kidney cancer and pneumothorax].

PMID- 22474783
TI  - [Horner syndrome is a serious complication in thyroid surgery. Dissection in
      nerve stimulation may be a risk factor, shown in three cases].

PMID- 22474784
TI  - [Red yeast rice can lower cholesterol but should not replace established
      therapy].

PMID- 22474785
TI  - [Valuable eye opener for interns].

PMID- 22474786
TI  - [Replica of testosterone campaign: Stop being a megaphone for Bayer].

PMID- 22474787
TI  - [Swedish Andrological Society on testosterone: misunderstood, mythical and a part
      of men's health].

PMID- 22474788
TI  - [Researching physicians built up the Swedish drug industry].

PMID- 22474789
TI  - Adjusting our moral compass. Ethical slips are tarnishing dentistry's public
      image.

PMID- 22474790
TI  - Did you see what they said about you online? When it comes to negative Internet
      postings, the remedies are few.

PMID- 22474791
TI  - More stay-at-home courses needed.

PMID- 22474792
TI  - Role of dental professional identification and referral of victims of domestic
      violence.
AB  - Dental professionals can play an important role in identifying and referring
      victims of domestic violence. Since most of the injuries sustained by victims
      occur in the head and neck region, dentists are uniquely positioned to help
      address this enormous public health issue. Unfortunately, dentists are the least
      likely of all health professionals to identify and refer victims of abuse. Much
      of this failure may be attributed to a lack of knowledge. This article provides
      an overview of the types and indicators of abuse, information about screening and
      interviewing victims, and referral resources.

PMID- 22474793
TI  - Prosthetic and surgical management of oronasal communications secondary to
      cocaine abuse.
AB  - Oronasal communications are serious sequelae of chronic cocaine abuse. If left
      untreated, these communications can severely limit a patient's quality of life.
      The defects can be rehabilitated successfully utilizing either maxillofacial
      prosthetics or various surgical techniques. Considerations in deciding between
      prosthetic and surgical approaches are discussed, as well as the basics of
      maxillofacial prosthetic rehabilitation and the different surgical techniques
      available. Photographic documentation of both maxillofacial prosthetic and
      surgical treatments performed by the authors is shown.

PMID- 22474794
TI  - Platelet-rich plasma. A review.
AB  - Platelet-rich plasma has been used in periodontal therapy because of its biologic
      characteristics in promoting wound healing and regeneration. Platelet-rich
      plasma, growth factors in platelet-rich plasma, their mechanism of action,
      probable role in wound healing, preparation of platelet-rich plasma and its
      activation are reviewed to provide insights into the role of this entity in wound
      healing and regeneration.

PMID- 22474795
TI  - The effect of oral motor exercises on patients with myofascial pain of
      masticatory system. Case series report.
AB  - Management of myofascial pain focuses on two goals: reducing pain and improving
      function in the muscles of mastication. A multidisciplinary treatment approach is
      typically used to help achieve these goals. The following case series report
      explores the impact of oral motor exercises on the management of myofascial pain
      when used in conjunction with other treatment modalities. Oral motor exercises
      are used by speech-language pathologists to improve the strength, range of
      movement and coordination of the oral musculature during non-speech movements.
      The findings of this case series report suggest an opportunity exists for
      collaboration between speech-language pathologists and the "traditional" TMD
      team.

PMID- 22474796
TI  - Survey of ambulatory surgery dentistry.
AB  - A telephone survey of New York State's most significant providers of Medicaid
      hospital ambulatory surgery dental treatment for special needs patients was
      conducted in June and July of 2011 to assess whether there had been changes in
      the availability of dental services following implementation of the Ambulatory
      Patient Groups (APG) Medicaid payment methodology and the April 2011 35%
      reduction in fee-for-service reimbursement to dentists who provide this dental
      care. With release of "Oral Health in America: A Report of the Surgeon General"
      in 2000, attention was focused on the link between oral health and general
      health, with the report highlighting the difficulties individuals with special
      needs experienced with respect to their oral health and accessing dental care.
      The New York State Department of Health in 2005 released its "Oral Health Plan
      for New York State." It had three stated objectives pertaining to those with
      special needs. None of these objectives has been met, and the response to this
      survey revealed waiting times for access to ambulatory surgery dental programs of
      up to two years and an overall probable 10% to 15% decrease in availability as a
      direct result of the APG payment methodology and reduction in fee-for-service
      reimbursements. New York is failing not only to meet the objectives of its own
      oral health plan, but also to adequately meet the dental health care needs of its
      most vulnerable citizens.

PMID- 22474798
TI  - Congenital epulis in newborn. Case report.
AB  - Congenital granular cell lesion, or congenital epulis, is a rare lesion of the
      newborn. The sight of a newborn infant with congenital epulis can be startling
      for both parents and healthcare professionals. The lesion appears most commonly
      in the maxillary alveolar ridge, with predominance in females. The etiology and
      histogenesis of the lesion remain obscure. This lesion can pose a risk of airway
      obstruction or can interfere with feeding. The report presented here describes a
      case of congenital granular cell lesion in the left maxillary region. The lesion
      was causing a feeding problem and, hence, was excised under local anesthesia.

PMID- 22474797
TI  - Illosis of maxillary sinus in immunocompromised patient. Case report.
AB  - Aspergillosis, which was first discovered in late 19th century, is a relatively
      rare disease in the sinuses. In recent years, a number of invasive aspergillosis
      infections of the maxillary sinus in immunocompromised patients, as well as the
      non-invasive form of the disease, have been reported. They were caused by the
      materials used in endodontic treatment, like gutta-percha, antrolith and by
      foreign bodies. This paper reports a case of aspergillosis in the maxillary sinus
      of an immunocompromised patient. It is associated with a root fragment after a
      much earlier tooth extraction.

PMID- 22474799
TI  - Management of a pulmonary artery embolectomy and recurrent embolus.
AB  - Pulmonary emboli are complex syndromes of altered coagulation and perfusion that
      remain prevalent among the population, especially the hospitalized. Adequate
      preparation by the clinicians and realization of the subtle yet potentially
      catastrophic nature of pulmonary emboli are critical when surgical intervention
      is required. This case report describes a 49-year-old woman with a diagnosis of
      massive pulmonary embolism who was brought to the operating room for emergent
      pulmonary artery embolectomy. Despite a profound Venouobstruction in her main
      pulmonary artery, she arrived in no acute distress and with stable hemodynamic
      values. During induction of general anesthesia, she quickly decompensated,
      requiring emergent cardiopulmonary bypass. Intraoperative transesophageal
      echocardiography guided the multistep surgery, resulting in the recognition of a
      recurrent right atrial embolus. The patient tolerated the procedure and
      ultimately had a favorable hospital course.

PMID- 22474800
TI  - Anesthetic management for implantation of a treatment device: the Rheos
      Baroreflex Hypertensive Therapy System.
AB  - Resistant hypertension is a prevalent dilemma. Despite all available
      antihypertensive medications and multiple strategies such as healthier diets and
      exercise programs, many patients are still unable to maintain or reach a
      therapeutic goal for systolic blood pressure. Because of this major health
      concern, CVRx, Inc has developed a treatment involving baroreflex activation
      therapy (Rheos Baroreflex Hypertension Therapy System) to treat patients with
      uncontrolled high blood pressure. The surgical implantation of this system is
      similar to a carotid endarterectomy procedure; however, the anesthetic management
      for this procedure is unique and challenging. This case report describes a 45
      year-old African American woman with a history of hypertension who was receiving
      multiple antihypertensive medications and, thus, was a qualified candidate for
      implantation of this device. The goal of anesthetic management during
      implantation of this hypertension therapy system is to preserve the carotid sinus
      baroreceptor sensitivity by avoiding administering anesthetic agents that inhibit
      the baroreceptor reflex during electrode placement and the testing period.
      Because of the restriction of some of the anesthetic agents that an anesthesia
      provider can use, this procedure poses major challenges to the anesthesia
      provider in planning for anesthesia care and managing risks to the patient.

PMID- 22474801
TI  - Simulation training for advanced airway management for anesthesia and other
      healthcare providers: a systematic review.
AB  - We studied the current literature on human patient simulation for preparing
      anesthesia and other healthcare providers for advanced airway management. A
      systematic review was conducted of articles published between 1990 and 2009 on
      advanced airway management for patients undergoing anesthesia and patients who
      are not. The search used 4 electronic databases: Cumulative Index to Nursing &
      Allied Health Literature, MEDLINE, PsycINFO, and Web of Science. We included 34
      articles in the analysis; 15 were experimental or quasi-experimental designs, 8
      descriptive studies and reports, and 11 analyses of equipment or technique
      evaluations using simulation. The majority of the studies included simulation
      education evaluation for a variety of medical, nursing, and allied health
      providers and students. Only 6 studies addressed the use of simulation as an
      educational or evaluation tool to enhance training of anesthesia providers in
      difficult airway management. Those studies included analyses of different types
      of training and the perceived value of simulated training, and evaluations of
      equipment. Few studies have analyzed the effects of this modality on trainer
      skills and patient safety. There is a clear need for well-designed studies to
      examine these effects.

PMID- 22474802
TI  - Myocardial infarction and pregnancy: a case report.
AB  - Coronary artery dissection is a rare, sometimes fatal traumatic condition, with
      80% of cases affecting women. The coronary artery develops a tear, causing blood
      to flow between the layers, which force them apart. We describe the case of a 35
      year-old multiparous woman with acute myocardial infarction secondary to right
      coronary artery dissection at 32 weeks' gestation. The patient underwent
      successful primary percutaneous coronary intervention with the placement of 4
      coronary stents. She subsequently experienced preterm labor and preeclampsia 11
      days following the procedure. Elective cesarean delivery under general anesthesia
      was performed uneventfully at 35 weeks' gestation.

PMID- 22474803
TI  - Anesthetic management of a pediatric patient undergoing a pancreatoduodenectomy
      with portal vein reconstruction.
AB  - A pancreatoduodenectomy involves the removal of a tumor from the head of the
      pancreas. It is a technically difficult procedure requiring experienced
      anesthesia and surgical teams. The addition of a portal vein reconstruction
      increases the complexity of the case. A pancreatoduodenectomy is rarely performed
      on pediatric patients. Although reports of pediatric pancreatoduodenectomies
      exist in the surgical literature, there are no reports in the anesthesia
      literature. Anesthesia providers must be prepared to manage these complicated
      cases because substantial fluid shifts, blood loss, and electrolyte disturbances
      may occur intraoperatively. We report the perioperative management of a pediatric
      patient undergoing this procedure.

PMID- 22474804
TI  - The use of high-fidelity simulation in the admissions process: one nurse
      anesthesia program's experience.
AB  - Nurse anesthesia programs across the country are frequently in search of better
      selection criteria and more efficient evaluation systems. The goal is to select
      qualified applicants who will successfully complete the program and represent the
      profession of nurse anesthesia. The primary method of assessing the quality of
      candidates' noncognitive attributes at the Oakland University Beaumont Program of
      Nurse Anesthesia (Royal Oak, Michigan) was by face-to-face interviews. The
      admissions committee believed that high-fidelity simulation may be a valuable
      tool to improve the overall admission process. For the 2008 application interview
      process, high-fidelity simulation was used as a method of simultaneously
      evaluating candidates' cognitive and noncognitive attributes, in addition to the
      traditional face-to-face interview. On completion of the admission interview
      process, a retrospective research design was used to identify a possible
      correlation between high-fidelity simulation performance scores and other
      candidate characteristics. The findings of this pilot study revealed a positive
      correlation between simulation and face-to-face interview scores, suggesting that
      candidates who exhibited desirable noncognitive attributes in the face-to-face
      interview also performed well in the simulation environment. The use of high
      fidelity simulation as an interview tool may provide an innovative adjunct for
      admission committees in assessment of candidates.

PMID- 22474805
TI  - Selective bilateral bronchial intubation for large, acquired tracheoesophageal
      fistula.
AB  - The anesthetic management of patients undergoing tracheoesophageal fistula repair
      often involves lung separation, usually selective bronchial intubation with a
      double-lumen endotracheal tube. However, in patients with airway fistulas arising
      below the tracheal lumen, selective lung ventilation and separation may require
      unusual methods of airway management. In the patient described in this report,
      the airway fistulas involved the distal 3 cm of the trachea, approximately half
      of the left main bronchus 1.5 cm beyond the carina, and the proximal 0.5 cm of
      the right main bronchus. To separate and ventilate the lungs during the repair of
      these large and complex airway fistulas, 2 individual Mallinckrodt microlaryngeal
      endotracheal tubes were used. While lung separation was achieved, contrary to
      previous reports, the Mallinckrodt's larger and more tapered cuff made
      positioning in the left main bronchus an ongoing issue that required the use of a
      conventional endotracheal tube and, eventually, intubation of the bronchus from
      the surgical field. Future cases involving complex airway fistulas should
      consider endotracheal tube limitations and other methods of providing ventilation
      such as high-frequency jet ventilation or cardiopulmonary bypass.

PMID- 22474806
TI  - Catecholamine-resistant hypotension following induction for spinal exploration.
AB  - Systemic blood pressure is regulated by 3 mechanisms: the sympathetic nervous
      system, the renin-angiotensin system, and the arginine-vasopressin system. The
      use of angiotensin II receptor blockers and angiotensin-converting enzyme
      inhibitors has become prevalent in the medical treatment of hypertension. These
      classes of medications inhibit the renin-angiotensin-aldosterone system,
      specifically the action of angiotensin II, a potent vasoconstrictor. This article
      describes the case of a 67-year-old man undergoing surgery for a spinal
      exploration who had hypotension following induction that was refractory to fluid
      administration and agents with mixed alpha-beta agonistic activity but responded
      to a vasopressin and phenylephrine infusion. Following the case study is a
      discussion of the impact that angiotensin II inhibitors may have on a patient
      undergoing general anesthesia and the role of vasopressin in reversing
      catecholamine-resistant hypotension.

PMID- 22474807
TI  - Awake craniotomy: a practice overview.
AB  - Craniotomies are a common neurological intervention for intracranial tumor
      resections. Anesthesia techniques allow surgeons to aggressively and optimally
      resect neoplastic tissue while sparing normal cerebral tissue. Awake craniotomies
      are surgical techniques that enable surgeons to avoid damaging normal cerebral
      regions and allow real-time patient feedback. Such surgical interventions would
      not be possible without anesthesia. The role of anesthesia providers is critical
      in gaining the trust and motivation of the patient. Preoperative evaluation,
      regional anesthesia, general anesthesia, and monitored anesthesia are necessary
      to achieve a successful surgical intervention with awake craniotomy. As awake
      craniotomy gains more popularity, dependable anesthesia techniques remain
      critical. A discussion follows of the role of anesthesia providers in awake
      craniotomy during the entire perioperative continuum.

PMID- 22474808
TI  - Serum C-reactive protein levels cannot be used to accurately assess the extent or
      severity of periodontal disease.

PMID- 22474810
TI  - "Uff da".

PMID- 22474809
TI  - My dental family.

PMID- 22474811
TI  - Destination: dentistry.

PMID- 22474812
TI  - Leaving Vietnam.

PMID- 22474813
TI  - The Molnar family.

PMID- 22474815
TI  - Texas ancestors and history.

PMID- 22474814
TI  - The Estes family.

PMID- 22474816
TI  - My story.

PMID- 22474817
TI  - Our ancestors, Puerto Rico and Texas.

PMID- 22474818
TI  - Helen Small.

PMID- 22474819
TI  - My journey.

PMID- 22474820
TI  - The family tradition.

PMID- 22474821
TI  - A dental family.

PMID- 22474822
TI  - A dental orchard.

PMID- 22474823
TI  - Oral and maxillofacial pathology case of the month. Multiple myeloma.

PMID- 22474824
TI  - What big teeth you have: images that get your patient's attention.

PMID- 22474825
TI  - Value for your profession: Why dentists need disability income insurance.

PMID- 22474826
TI  - Innovative unit leads the way.

PMID- 22474827
TI  - Emergency frailty unit helps get patients home quicker.

PMID- 22474828
TI  - Pros and cons of assisted dying.

PMID- 22474829
TI  - What can I do to help an older person who is experiencing anxiety?

PMID- 22474830
TI  - Redesigning wards to support people with dementia in hospital.
AB  - The Enhancing the Healing Environment programme is a nurse-led initiative,
      devised by charity the King's Fund, to encourage staff to work in partnership
      with patients to improve the environment in which they deliver care. This article
      explores projects that have developed as part of the programme that focus on
      dementia and acute care. A case study of work undertaken at Bradford Royal
      Infirmary is included to show the benefits to staff and patients of improving
      their surroundings.

PMID- 22474831
TI  - How to optimise the registered nurse contribution in care homes.
AB  - This article aims to offer ideas that may be useful to care homes when
      considering priorities for registered nurse (RN) work. Drawing on the findings of
      research into the work of RNs and care assistants in UK care homes (Heath 2006),
      it discusses the distinct contribution of RNs, the delegation of nursing
      interventions and the need for a 24-hour RN presence. International debates on
      the distinct contribution of RNs in residential settings for older people are
      also acknowledged.

PMID- 22474832
TI  - Creating activities in care homes.
AB  - The provision of meaningful activities in care homes can be challenging because
      of the differing needs and interests of residents. This article examines the work
      of the National Association for Providers of Activities for Older People (NAPA),
      a charity which trains and supports care staff to integrate activity into the
      daily lives of residents. NAPA's work focuses on the need to develop a creative
      and individualised approach. Staff at one care home discuss the support they
      provide so residents can engage in a variety of activities.

PMID- 22474833
TI  - Nurses' perceptions of their role in rehabilitation of the older person.
AB  - AIM: The aim of the study was to explore nurses' perceptions of their role in
      rehabilitation of the older person. METHOD: Nine participants were interviewed in
      two rehabilitation units in Ireland. Data were transcribed and analysed using
      Colaizzi's (1978) framework. FINDINGS: Three main themes emerged: care delivery,
      collaboration and autonomy/empowerment. CONCLUSION: Nurses have an important role
      in the rehabilitation of older people, which is often undervalued and ill
      defined. Nurses need to recognise and articulate their contribution and value.

PMID- 22474834
TI  - [Helicopter parents].

PMID- 22474835
TI  - [Staffing resources in nursing: higher rate of complications with deficit of
      nursing staff].

PMID- 22474836
TI  - [Effects of puerperal depression on the child].

PMID- 22474837
TI  - [First cystic fibrosis nursing continuing education in Austria].

PMID- 22474838
TI  - [Disinfection requirements in punctures and injections: new recommendation of the
      Robert Koch Institute].

PMID- 22474839
TI  - [Adoptive breast feeding].

PMID- 22474840
TI  - ["Discovering the world". Art projects with students of an elementary school as
      well as a special education school with mental development as the teaching
      emphasis].

PMID- 22474841
TI  - [Fine Star honors engagement for children and adolescents with diabetes].

PMID- 22474842
TI  - [A Chamber of Nursing for Bavaria].

PMID- 22474843
TI  - [More help in crises during pregnancy is necessary].

PMID- 22474844
TI  - [Individual health information under scrutiny: the new "IGeL Monitor" internet
      site informs about value and risks].

PMID- 22474845
TI  - [ADHD: training brain performance with the computer helps].

PMID- 22474846
TI  - [100 errors in direct nursing care and in collaboration with medical therapy and
      diagnosis (interview by Hardy-Thorsten Panknin)].

PMID- 22474847
TI  - [Nursing education only with diploma? The European Union exerts pressure].

PMID- 22474848
TI  - [Better education means greater attractiveness. Change in the guidelines for
      professional recognition on the EU level].

PMID- 22474849
TI  - [Eliminating free play hurts children. Psychologists warn about full schedules
      and excessive caution].

PMID- 22474850
TI  - [Topical antibiotic stops tick disease. Gel gives hope for simplified prevention
      of Lyme borreliosis].

PMID- 22474851
TI  - [Lucky Hanschen later becomes fortunate Hans. Psychologically resilient children
      have better chances as adults].

PMID- 22474852
TI  - ["Basic hospital hygiene competence" (interview Hardy-Thorsten Panknin)].

PMID- 22474853
TI  - New year, new beginnings.

PMID- 22474854
TI  - The impact of maternal depression on children with asthma.
AB  - This integrative literature review focuses on the impact of maternal depression
      on children with asthma. Maternal depression has a negative impact on a child's
      growth, development, behavior, mental health, safety, and health care
      utilization. Mothers of children with chronic conditions such as asthma have
      higher rates of depression compared to mothers of children without a chronic
      condition. Research has shown that maternal depression has the potential to
      increase asthma morbidity and health care utilization. In addition, mothers with
      depressive symptoms report lower self-efficacy in their ability to care for their
      children with asthma, which can affect their ability to manage their child's
      asthma with the prescribed medication regimen. To provide optimal care for
      children with asthma and their families, pediatric care providers must perform
      periodic depression screening to mothers or caregivers. Depressed mothers or
      caregivers of children with asthma require care coordination and management that
      consists of increased education on asthma and depression, and more frequent
      follow up than families without maternal/caregiver depression. These additional
      care measures have numerous positive benefits, including enhancing the quality of
      life in both the child and caregiver by improving asthma management in the child
      and depressive symptoms in the mother, as well as decreasing costs imposed on the
      economy through reduced emergency department visits, hospitalizations, missed
      work days, and missed school days.

PMID- 22474855
TI  - Life concerns and perceptions of care in adolescents with mental health care
      needs: a qualitative study in a school-based health clinic.
AB  - Health clinics within schools are designed to provide comprehensive care to the
      student population. Little research has been conducted to identify how
      effectively school-based health clinics are meeting the mental health needs of
      adolescents. This qualitative study explored the perceptions of mental health
      needs of 18 inner-city teens between 12 to 18 years of age with diagnosed
      behavioral or mental health issues. A single, face-to-face, semi-structured
      interview was used to examine students' concerns and attitudes toward their
      health care needs and services. Results revealed concern for their personal and
      family relationships, education and vocational goals, health maintenance, and
      financial independence. Most pressing resource needs related to their ability to
      receive health maintenance and coping skills and to adapt to complex life
      challenges they faced in their urban neighborhood. Participants remarked that if
      the clinic did not identify their needs for mental health care, they would most
      likely have not received services. When mental health care needs were identified,
      individual counseling was used to support dialogues for optimal mental and
      physical health.

PMID- 22474856
TI  - The epidemiology of falls in hospitalized children.
AB  - This study was conducted to validate the CHAMPS pediatric fall risk assessment
      tool for hospitalized children. At the time of this study, there was a lack of
      published evidence for a valid pediatric fall risk assessment tool for
      hospitalized children. Adult instruments were the only valid tools for fall risk
      assessment, and they were being used in populations where the validity had not
      been established. A prospective cohort study was conducted to analyze the
      sensitivity and specificity of the CHAMPS pediatric fall risk assessment tool.
      Analysis was conducted to further establish validity. The CHAMPS instrument had a
      sensitivity of 0.75 and a specificity of 0.79, with a relative risk of 3.5,
      excess risk of 200%, and an odds ratio of 10.8. This instrument can be
      categorized as moderate to strong in prediction of pediatric falls, while
      specificity was found to be slightly stronger than sensitivity.

PMID- 22474857
TI  - Timing of adiposity rebound: a step toward preventing obesity.
AB  - Adiposity rebound (AR) is used as an indicator to predict obesity in adults.
      Previous studies about AR in the U.S. were based on local data; therefore, the
      generalizability of study results is limited. The purpose of this study was to
      identify the timing of AR for U.S. children using a national survey data set, the
      National Health and Nutrition Examination Survey (NHANES). Combined data of
      NHANES 1999-2008 were used to estimate the national level of this critical period
      for U.S. children developing obesity. Data of 8813 children 2 to 10 years of age
      were analyzed. Mean body mass index was estimated using the survey sample
      analysis method. Visual inspection method was employed to examine the timing of
      AR. Gender and race/ethnicity differences in AR were identified at an early age.
      AR occurred earlier in girls and in Non-Hispanic African-American children than
      in Non-Hispanic Caucasian children. Differences in timing for AR by gender and
      race/ethnicity should be considered in planning early and timely intervention
      efforts to prevent childhood obesity.

PMID- 22474858
TI  - Demystifying research: uncovering important information.

PMID- 22474859
TI  - Implementing patient- and family-centered care: part I--understanding the
      challenges.

PMID- 22474860
TI  - The high cost of free drug samples.

PMID- 22474861
TI  - To circ or not: a reappraisal.
AB  - Routine circumcision remains a topic of controversy. The most recent male
      circumcision policy from the American Academy of Pediatrics argued that data were
      insufficient to recommend routine circumcision. Recent trials in Africa
      evaluating male circumcision for the prevention of sexually transmitted diseases
      have, however, revived the circumcision controversy.

PMID- 22474862
TI  - Traces: making sense of urodynamics testing--Part 9: Evaluation of sensations
      detrusor response to bladder filling.
AB  - Part 9 of the Traces series continues the discussion of how urodynamic clinicians
      generate usable data from a filling cystometrogram. This article focuses on the
      question: "What is the detrusor's response to bladder filling?" Answering this
      question requires the clinician to identify and differentiate detrusor
      contractions from abdominal events, artifacts, or low bladder wall compliance;
      documentation of the volume of the contraction; and assessment of its clinical
      relevance as an overactive or subclinical detrusor contraction.

PMID- 22474863
TI  - A review of strategies to decrease the duration of indwelling urethral catheters
      and potentially reduce the incidence of catheter-associated urinary tract
      infections.
AB  - The use of indwelling urinary catheters in hospitalized patients presents an
      increased risk of the development of complications, including catheter-associated
      urinary tract infection (CAUTI). With regard to the risk of developing a CAUTI,
      the greatest factor is the length of time the catheter is in situ. The aim of
      this article is to review the evidence on the prevention of CAUTI, particularly
      ways to ensure timely removal of indwelling catheters. Published studies
      evaluating interventions to reduce the duration of catheterization and CAUTI in
      hospitalized patients were retrieved. The research identified two types of
      strategies to reduce the duration of indwelling urinary catheters and the
      incidence of CAUTI: nurse-led interventions and informatics-led interventions,
      which included two subtypes: computerized interventions and chart reminders.
      Current evidence supports the use of nurse-led and informatics-led interventions
      to reduce the length of catheterizations and subsequently the incidence of CAUTI.

PMID- 22474864
TI  - Efficacy of solifenacin for overactive bladder symptoms, symptom bother, and
      health-related quality of life in patients by duration of self-reported symptoms:
      a secondary analysis of the VIBRANT study.
AB  - In this post-hoc analysis of data from patients with overactive bladder (OAB) in
      VIBRANT patients receiving solifenacin showed statistically significantly greater
      improvement versus placebo in most outcome measures regardless of OAB symptom
      duration (less than five years and five years or longer).

PMID- 22474865
TI  - Adding to the evidence base: efficacy of solifenacin for overactive bladder
      symptoms, symptom bother, and health-related quality of life in patients by
      duration of self-reported symptoms: a secondary analysis of the VIBRANT study.

PMID- 22474866
TI  - "I don't do maintenance".

PMID- 22474867
TI  - Two stealth triumphs in global health.

PMID- 22474868
TI  - Imaging issue: part I.

PMID- 22474869
TI  - Tracheobronchomalacia.

PMID- 22474870
TI  - MRI of acute appendicitis in the pregnant patient.

PMID- 22474871
TI  - Pediatric omental infarction.

PMID- 22474872
TI  - Glioblastoma multiforme: utilization of advanced MRI techniques for preoperative
      planning.

PMID- 22474873
TI  - Focal nodular hyperplasia on MRI using a hepatocyte-specific contrast agent at
      1.5 Tesla vs. 3.0 Tesla field strength.

PMID- 22474874
TI  - Cardiac CT angiography of an anomalous intramuscular left main coronary artery.

PMID- 22474875
TI  - Ingested foreign body in the sigmoid colon: detection and localization by CT
      colonography.

PMID- 22474876
TI  - Microwave ablation for lung cancer.

PMID- 22474877
TI  - Rheumatoid arthritis demonstrated on PET/CT as the etiology of hypercalcemia.

PMID- 22474878
TI  - Benign ovarian serous cystadenoma mimicking papillary thyroid carcinoma
      metastasis on I-131 SPECT/CT.

PMID- 22474879
TI  - Stroke salvage using a suction thrombectomy device and tissue plasminogen
      activator.

PMID- 22474880
TI  - Atypical insufficiency type femoral stress fractures in patient on
      bisphosphonates.

PMID- 22474881
TI  - Discussion of health topics during prenatal care in Rhode Island.

PMID- 22474882
TI  - Words in the spiritual domain.

PMID- 22474883
TI  - The storm's aftermath.

PMID- 22474884
TI  - Feeling the pinch.

PMID- 22474885
TI  - Losing independence.

PMID- 22474886
TI  - Rx for health: a home.

PMID- 22474887
TI  - Stories from a struggling economy.

PMID- 22474888
TI  - The arm that was not broken. A lesson on cost and quality of health care.

PMID- 22474889
TI  - State delays release of provider peer grouping report.

PMID- 22474890
TI  - MMA warns against "pox parties".

PMID- 22474891
TI  - Moving forward.

PMID- 22474892
TI  - Responding to tough times.

PMID- 22474894
TI  - The physician's role in health care spending.
AB  - Physicians must weigh their obligation to provide their patients with the best
      care possible against their obligation to be good stewards of health care
      resources. Given the rising cost of health care in the United States and
      Minnesota, striking the right balance has become more of a challenge. This
      article describes national and state health care spending trends. It also
      describes the State of Minnesota's Provider Peer Grouping program and the health
      plans' total cost of care analyses, two initiatives that are being used to
      evaluate the cost of care delivered by various provider groups and highlight
      areas for improvement.

PMID- 22474895
TI  - Rescued by the safety net.
AB  - The recent recession had a significant impact on the nation and Minnesota both in
      terms of the number of jobs lost and the loss of employer-sponsored health
      insurance (ESI). In this article, we present national and Minnesota-specific data
      on the loss of ESI. We also explore how government-sponsored programs provided a
      safety net that enabled many people with low incomes to retain health insurance
      coverage, lessening the recession's impact in Minnesota. We conclude with general
      comments about the role of the safety net in a health care system in which the
      majority of people have health care coverage through voluntary employer-based
      programs.

PMID- 22474896
TI  - Improving the health of the homeless: advice for physicians.
AB  - Homeless individuals suffer from a constellation of health issues, experience
      barriers to medical care that are both recognizable and hidden, and score worse
      on measures of health outcomes than the general population. They differ to such
      an extent from the general population that homeless people should be viewed by
      clinicians as a unique patient population. Improving the health of this
      population is difficult for a number of reasons. This article explores those
      reasons. It describes common conditions affecting homeless people and discusses
      how patient-centered comprehensive primary care, collaboration between health
      care providers and social service organizations, and innovative delivery of
      medical respite services can result in better care for this population.

PMID- 22474898
TI  - The bully's pulpit.

PMID- 22474897
TI  - Impact of the recession on Minnesota's health care market.
AB  - Historically, health care spending has not been very sensitive to short-term
      economic disruptions. However, data show some notable changes in health care
      spending and utilization since the recession of 2007-2008 both nationally and in
      Minnesota. This article presents trends emerging from that data and discusses
      potential reasons for them. It also highlights other factors such as structural
      changes in health care delivery that were occurring before, during, and after the
      economic downturn, that might account for the trends.

PMID- 22474899
TI  - The best web resources for heat problems.

PMID- 22474900
TI  - Hearing conservation in 2012: focus on NRR.

PMID- 22474901
TI  - A game plan for these tough times.

PMID- 22474902
TI  - Hazard material information management and regulatory compliance.

PMID- 22474903
TI  - Do I really need 40 hours? Hazwoper training exposed.

PMID- 22474904
TI  - FAA takes aim at pilots' fatigue.

PMID- 22474905
TI  - Improving your workplace violence prevention program.

PMID- 22474906
TI  - Mobile phones in hospital settings: a serious threat to infection.

PMID- 22474907
TI  - Matching your organizational culture to the safety mission.

PMID- 22474908
TI  - Plan, train, and maintain for safety success.

PMID- 22474909
TI  - It's all about attitude.

PMID- 22474910
TI  - The upside to explaining benefits.

PMID- 22474911
TI  - Shortcut safety leadership.

PMID- 22474912
TI  - The social determinants of depression in elderly Korean immigrants in Canada:
      does acculturation matter?
AB  - Depression in old age significantly decreases the quality of life and may lead to
      serious consequences, such as suicide. Existing literature indicates that elderly
      Korean immigrants may experience higher levels of depression than other racial
      ethnic group elders. The purpose of this exploratory study was to investigate
      factors that influence depression among older Korean immigrants in Toronto. A
      total of 148 participants, ages 60 years or older (mean age = 74.01, SD = 8.24),
      completed face-to-face interviews in Korean language. Hierarchical regression
      analyses were conducted by adding variables in three steps: (1) demographic
      variables; (2) acculturation variables (years of immigration and English
      proficiency); and (3) social determinants (social integration variables, physical
      health, and financial satisfaction). Results showed that acculturation factors
      were not associated with depression. Instead, social determinants variables,
      including lower physical health status and lower financial status, living alone,
      and lower level of social activity, predicted higher level of depressive
      symptoms, along with lower education. The final regression model explained about
      37% of variance of depression in the sample. These results suggest that social
      determinants, not acculturation, are important factors explaining the levels of
      depression in Korean immigrant elders living in a metropolitan city in Canada.
      Implications for practice are discussed.

PMID- 22474913
TI  - Age differences in attention toward decision-relevant information: education
      matters.
AB  - Previous studies suggested that older adults are more likely to engage in
      heuristic decision-making than young adults. This study used eye tracking
      technique to examine young adults' and highly educated older adults' attention
      toward two types of decision-relevant information: heuristic cue vs. factual
      cues. Surprisingly, highly educated older adults showed the reversed age pattern
      they looked more toward factual cues than did young adults. This age difference
      disappeared after controlling for educational level. Additionally, education
      correlated with attentional pattern to decision-relevant information. We
      interpret this finding as an indication of the power of education: education may
      modify what are thought to be "typical" age differences in decision-making, and
      education may influence young and older people's decision-making via different
      paths.

PMID- 22474914
TI  - Aging well socially through engagement with life: adapting Rowe and Kahn's model
      of successful aging to Chinese cultural context.
AB  - Although aging well socially (engagement with life) is as important as aging well
      personally (illness avoidance and functioning) (Rowe & Kahn, 1998), it has
      received less research attention. A caring (CE) and a productive (PE) form of
      engagement were derived from an analysis of Chinese cultural meanings of
      engagement, and combined with illness avoidance and functioning to form a 4
      factor model. Confirmatory factor analysis based on 2970 Hong Kong Chinese (40 to
      74 years) showed a good model fit that was replicated a year later with 2120 of
      the original sample. Further analysis led to a more parsimonious model where
      illness avoidance and functioning converged into a single second-order factor
      whereas CE and PE remained as distinct first-order factors. The results supported
      the differentiation of Rowe and Kahn's engagement with life component into caring
      and productive engagements.

PMID- 22474915
TI  - Age-differences in work motivation and job satisfaction. The influence of age on
      the relationships between work characteristics and workers' outcomes.
AB  - This study investigated the influence of age on the relationship between work
      characteristics and workers' work motivation and job satisfaction. In total, 1036
      workers of a Dutch division of a multinational organization participated. Data
      were collected by a digital questionnaire. Two interaction terms in the
      regression on work motivation were significant. The first interaction showed that
      the positive correlation between Motivating Potential Score (MPS) and motivation
      was much stronger for older than for younger employees. So, to remain motivated,
      older employees seem more in need of intrinsic challenging and fulfilling jobs.
      The second significant interaction indicated that the positive association
      between career opportunities and motivation was much stronger for younger
      employees than for older employees. This means that, especially, younger workers'
      motivation increases as they are offered more career opportunities. Careful
      career mentoring by the supervisor as part of an aging policy can contribute to
      the maintenance of workers of any age.

PMID- 22474916
TI  - A salutogenic analysis of developmental tasks and ego integrity vs. despair.
AB  - This study examines the hypothesis that the outcome of the Eriksonian crisis of
      integrity vs. despair is dependent on successful coping with four developmental
      tasks: maintenance of active involvement, reevaluation of life satisfaction,
      developing a sense of health maintenance, and reevaluation of the sense of
      coherence (SOC). A selective sample of 170 rather healthy individuals at the mean
      age of 67 years filled out a questionnaire assessing everyday activities,
      satisfaction with past, present, and future life, healthy habits, SOC, and
      depression. In our final path-analytical model, the SOC had a significant direct
      effect on all endogenous variables; it also attenuated depression indirectly via
      activity and via satisfaction with present and future life. Satisfaction with
      present life showed the strongest mitigating direct effect on depression. The SOC
      is an important antecedent for successfully resolving the integrity vs. despair
      crisis, in that a strong SOC is a guiding force behind mastering the other three
      tasks.

PMID- 22474917
TI  - Nocturnal regrets and insomnia in elderly people.
AB  - Despite their importance for general health, emotion-related factors have rarely
      been considered in the etiology of late-life insomnia. This study explored the
      relations between impulsivity, regret experiences, use of different thought
      control strategies, and insomnia severity in a sample of older adults whose age
      ranged from 51 to 98 years. Results revealed that: (a) regret frequency varies
      across the hours of the day, with a peak in the evening when people are trying to
      fall asleep; (b) individuals scoring high on impulsive urgency are particularly
      prone to experience nocturnal regrets; (c) nocturnal regrets are associated with
      insomnia severity, independently of other well-known risk factors such as
      depression, sleep-interfering medical conditions, and medications; and (d) the
      thought-control strategies of self-attacking, thought suppression, and worry are
      positively associated with the frequency of nocturnal regrets and insomnia
      severity. These findings indicate that dysfunctional regret regulation plays an
      important role for sleep disturbances in elderly people.

PMID- 22474918
TI  - As we head into the future in nursing.

PMID- 22474919
TI  - Implementing the SOHN-endorsed AORN guidelines for reprocessing reusable upper
      airway endoscopes.
AB  - This is a companion paper to two previous publications on recommended practices
      for cleaning and reprocessing flexible endoscopes used in Otolaryngology
      (Burlingame, Arcilla, & McDermott, 2008; Adams & Baker, 2010). In this paper we
      capture and expand upon the audience question and answer session in which the
      Society of Otorhinolaryngology and Head-Neck Nurse (SOHN)--endorsed the
      Association of periOperative Registered Nurses (AORN) recommended practices were
      presented to the SOHN membership (Adams & Waddington, September, 2010). We
      include additional background information to assist readers in understanding some
      of the science behind the recommendations and share successful implementation
      strategies from Otorhinolaryngology (ORL) outpatient nurses and published
      references.

PMID- 22474920
TI  - Body image reintegration and coping effectiveness after head and neck surgery: a
      review.

PMID- 22474921
TI  - The hidden member benefit.

PMID- 22474922
TI  - Controlling your health care costs: individual health care plans.

PMID- 22474923
TI  - Dentistry: a profession at the crossroads. 2.

PMID- 22474924
TI  - Deja vu indeed--and the beating of a dead (Trojan) horse.

PMID- 22474925
TI  - Differential diagnosis of oral lesions in geriatric patients.

PMID- 22474926
TI  - Diagnostic discussion. Orthokeratinized odontogenic cyst.

PMID- 22474927
TI  - Significance of cannabis use to dental practice.
AB  - The illicit use of the three main forms of cannabis--marijuana, hash, hash oil-
      pose certain obstacles and challenges to the dental professional. There are a
      number of systemic, as well as oral/head and neck manifestations, associated with
      cannabis use. Dentists need to be aware of these manifestations in order to take
      whatever precautions and/or modifications to the proposed treatment that might be
      necessary.

PMID- 22474928
TI  - Q&A with Dentist of the Year Dr James Antoon.

PMID- 22474929
TI  - Colour match between porcelain and porcelain-repairing resin composites.
AB  - The aim of this study was to evaluate the differences in colour between dental
      porcelain and porcelain-repairing resin composites. Porcelain discs were
      fabricated using four dentine shades in 1mm and 2mm thicknesses. Another series
      of discs was fabricated in 1mm and 2 mm thicknesses using three different brands
      of composite. Four single shades were used for the 1mm thick discs, and four
      single and 12 combined shades for the 2mm thick discs. The colour was measured
      using a spectrophotometer and colour differences deltaE* were calculated between
      samples. Colour differences were in the range of (deltaE* = 3.5-26.9), above the
      accepted threshold for perceptibility (deltaE* > 1) with a number above the
      threshold for what is considered to be clinically acceptable (deltaE* > 5.5).
      Improvements in colour match were seen for certain shade combinations of
      repairing composites, in contrast to when a single shade of composite was used.

PMID- 22474930
TI  - Effect of welding parameters of the Nd:YAG laser on the penetration depth of
      cobalt chromium alloys.
AB  - The aim of the investigation was to study the effect of the laser welding
      parameters of energy and spot diameter on the penetration depth of the weld of
      cast Co-Cr alloy when a single weld was performed. Within the limitations of the
      study as voltage increased and the spot diameter decreased, penetration depth
      increased. However, SEM investigation showed more defects in the welded area
      under these circumstances. The clinical significance is that during selection of
      the welding parameters the thickness of the components to be welded should be
      considered to achieve an extended welded area without the induction of micro
      structural defects.

PMID- 22474931
TI  - Stabilization splint treatment on complete denture--two reported cases.
AB  - The pre-prosthetic treatments of two female patients with osteoarthritis of the
      temporomandibular joints were presented in this paper. In the first case report,
      an 83-year-old patient wore complete dentures (CDs) for 30 years. The second
      patient (71 years of age) wore a three-year-old upper CD and a lower removable
      partial denture with a two-unit fixed dental prosthesis. Pain was successfully
      eliminated by the stabilization splint on the upper CD. Magnetic resonance
      imaging was used to confirm the diagnosis and clinical follow-up of the splint
      treatment.

PMID- 22474932
TI  - Accuracy of shade matching performed by colour blind and normal dental students
      using 3D Master and Vita Lumin shade guides.
AB  - The purpose of this study was to investigate whether 3D Master or VitaLumin shade
      guides could improve colour selection in individuals with normal and defective
      colour vision. First, colour perception of 260 dental students was evaluated.
      Afterwards, 9 colour blind and 9 matched normal subjects tried to detect colours
      of 10 randomly selected tabs from each kit and the correct/false answers were
      counted. Of the colour-defective subjects, 47.8% and 33.3% correctly detected the
      shade using 3D Master and VitaLumin, respectively. These statistics were 62.2%
      and 42.2% in normal subjects. In normal participants, but not in colour blind
      ones, 3D Master significantly improved shade matching accuracy compared to
      VitaLumin.

PMID- 22474933
TI  - Correlation between dental arch location and clinical success rate of total etch
      and self-etch adhesives in ClassV composite restorations.
AB  - Flexure at the tooth cervix might render the restored Class V lesions to
      degradation. In this clinical trial a total of 76 carious cervical lesions in
      both arch were restored using Prime & Bond NT and Clearfil SE Bond adhesives,
      along with Clearfil APX composite resin. Retention of restoration, marginal
      discoloration and postoperative sensitivity were evaluated during a one year
      period. The overall clinical success rate was 89.5%, while no significant
      difference (p > 0.05) was found regarding postoperative sensitivity or marginal
      discoloration between two adhesives. Retention loss was associated only with self
      etch adhesives. No association was found between clinical success and dental arch
      location.

PMID- 22474934
TI  - Trends in material choice for direct restorations by final year students from
      University College Cork 2004-2009.
AB  - Traditionally, undergraduate students in University College Cork (UCC) have been
      taught to use amalgam as the first choice material for direct restoration of
      posterior cavities. Since 2005 the use of composite resins has replaced amalgam
      as the first choice material. An audit was conducted of all direct restorations
      placed by final year students from UCC from 2004 until 2009. Results showed that
      over a six year period, final year UCC dental undergraduate students placed
      proportionately more direct composite resin restorations and significantly fewer
      amalgam restorations. The need for and undergraduate exposure to, provision of
      amalgam restorations may have to be revisited.

PMID- 22474935
TI  - Evaluation of splinting implant impression techniques: two dimensional analyses.
AB  - This paper aims to evaluate the effect of splinting during implant impression. A
      master model with two fixtures at the sites of 45 and 47 was used. 20 impressions
      were made for all four techniques: (A) indirect; (B) direct, unsplinted; (C)
      direct, splinted; and (D) direct, splinted, sectioned, and re-splinted. Splinting
      was undertaken with autopolymerizing acrylic resin (AAR). Horizontal distance
      between fixtures was compared using a digital caliper. The difference in distance
      were analysed with one-way ANOVA. Group A showed a significantly lowest accuracy
      among all techniques (p < or = 0.05). There was no significant difference of
      accuracy among the groups using direct techniques (p > or = 0.05). Group D was
      more accurate compared to group B and C. We conclude that splinting of impression
      copings would be beneficial to obtain an accurate impression.

PMID- 22474936
TI  - Effects of different pretreatments on the bond strength of a dual-cure resin core
      material to various fiber-reinforced composite posts.
AB  - The aim of this study was to evaluate the effects of different pretreatments on
      the bond strength of a dual-cure resin core to 3 types of fiber posts. Bond
      strength was measured using a push-out design. One-sided t-Test of Hypothesis
      with unknown variance was performed (p-values < 5%). Sandblasting abrasion with
      50 micro alumina particles at a specific distance, pressure and time was the only
      surface treatment in DT Light Post and Transluma Post that increased the bond
      strength to dual cure resin composite cores. FRC Postec Plus post did not shown
      an increase in bond strength in any group.

PMID- 22474937
TI  - Antiviral furanosesquiterpenes from Commiphora erythraea.
AB  - The crude methanolic extract obtained from C. erythraea resin was chromatographed
      on silica gel with solvent of increasing polarity. The extract and fractions were
      evaluated for cytotoxicity and antiviral activity [parainfluenza type 3 virus
      (PIV3)] by plaque forming units (PFU) reduction assay using HEp-2 cells (human
      larynx epidermoid carcinoma cell line). From the active fraction, five compounds
      were isolated and tested. Only two of these showed anti-PIV3 activity with a
      selectivity index (SI) of 66.6 and 17.5, respectively. Both the compounds are
      furanosesquiterpenoids.

PMID- 22474938
TI  - Sesquiterpenes from the inner bark of the silver birch and the paper birch.
AB  - The compositions of the mixtures of sesquiterpenoids, largely hydrocarbons that
      were found in the inner bark of the silver birch, Betula pendula Roth and the
      paper birch, Betulapapyrifera Marshall, grown in New Zealand were analyzed by
      SPME-GCMS. The major components of the volatile oil from the inner bark of B.
      pendula were trans alpha-bergamotene (31%) and alpha-santalene (19%). This
      composition was quite different from that of the oil from the branches, buds and
      leaves of the same species from Turkey, but was very similar to that of the oil
      from the bark of B. pubescens from Russia. The major components of the oil from
      the inner bark of B. papyrifera were trans alpha-bergamotene (18%), ar-curcumene
      (12%), E-beta-farnesene (12%), Z-beta-farnesene (10%) and cis-alpha-bergamotene
      (8%).

PMID- 22474939
TI  - Two new ballonigrin-type diterpenoids from the roots of Ballota limbata.
AB  - Two new ballonigrin type lactone diterpenoids, named ballonigrin lactone A and B,
      have been isolated from the roots of Ballota limbata. Structure elucidation of
      the isolated compounds was based on spectroscopic {IR, 1H- and 3C-NMR, and 2D-NMR
      (HMQC, HMBC, COSY and NOESY} and EI-MS data.

PMID- 22474940
TI  - A novel anticancer diterpenoid from Jatropha gossypifolia.
AB  - Jatropha gossypifolia root bark is used in ethnomedicine for bacterial infections
      and cancer of the lungs. Phytochemical investigation resulted in the isolation
      and characterization of a potent anticancer and novel lathyrane diterpenoid
      compound, abiodone, with an unusual methylene group. The structure of this novel
      compound was established by 1D, and 2D NMR spectroscopic experiments a nd
      confirmed by X-ray analysis.

PMID- 22474941
TI  - Antihepatitis B virus constituents of Solanum erianthum.
AB  - Eleven compounds were isolated from the methanolic extract of the leaves of
      Solanum erianthum D. Don, including five alpha-linolenic acid analogs, alpha
      linolenic acid (1), 13S-hydroxy-9(Z),11(E)-octadecadienoic acid (2), 9S-hydroxy
      10(E),12(Z), 15(Z)-octadectrienoic acid (3), 9(Z),11(E)-octadecadienoic acid (4),
      and octadecanoic acid (5); two benzofuran-type lactones, loliolide (6) and
      dihydroactinidiolide (7); two steroidal alkaloids, solasonine (8) and solamargine
      (9); a flavonol glycoside, camelliaside C (10); and a flavone, 5-methoxy-(3,4"
      dihydro-3",4"-diacetoxy)-2",2'-dimethylpyrano-(7,8:5",6")-flavone (11). Among
      these isolated compounds, 9 showed the most potent activity against HBsAg, with
      an IC50 of 1.57 microM, followed by 8 (IC50 is 5.89 microM). In the testing
      against HBeAg, 11 was the only active compound with an IC50 of 36.11 microM.
      Compound 9 also revealed strong inhibition of DNA replication towards HBV and its
      IC50 was 2.17 microM. However, alpha-linolenic acid (1) showed a prominent
      selected index (SI), both in anti-HBsAg and inhibition of DNA replication with SI
      values of 7.75 and 7.18, respectively. This is the first report that unsaturated
      fatty acid 1, steroidal alkaloid glycoside 9 and flavone 11, all showed excellent
      activity against HBV. These results provide lead candidates in the development of
      anti-HBV drugs from natural sources.

PMID- 22474942
TI  - Physical properties and molecular conformations of indole alkaloids and model
      protein interactions--theoretical vs. experimental study.
AB  - The physical properties and molecular structure of five natural indole alkaloids
      (IAs) and their interaction with protein targets have been studied,
      experimentally and theoretically. Electronic absorption (EAs) and CD
      spectroscopy, electrospray ionization (ESI) and matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS), as well as imaging mass
      spectrometric techniques (IMS) were used, analyzing the isolated alkaloids and
      corresponding IAs/protein molecular complexes. Theoretical quantum chemical DFT
      calculations were also applied. The mechanism of their biological activity and
      structure-activity relationship as potential neurologically active compounds were
      studied, using the model interactions with 5HT2A receptors. The gas-phase stable
      molecular fragments of the IAs are discussed comparing the experimental mass
      spectrometric data and theoretical quantum chemical DFT calculations of the
      different molecular fragments of the IAs.

PMID- 22474943
TI  - Antiparasitic and anticancer constituents of the endophytic fungus Aspergillus
      sp. strain F1544.
AB  - With the combined goal of finding the best anti-parasitic and anti-cancer
      activities as well as isolating the bioactive agents and studying their
      structures and biological properties, we proceeded to perform a small-scale
      cultivation of Aspergillus sp. strain F1544 using Potato Dextrose, Malt Extract,
      Czapek Dox and Eight Vegetables media. From the more promising extracts
      (obtaining using potato dextrose and czapek dox media in large scale) of this
      fungus, we isolated the five compounds: pseurotin A (1), 14-norpseurotin A (2),
      FD-838 (3), and pseurotin D (4), and fumoquinone B (5). All compounds showed good
      antileishmanial and moderate anticancer activities.

PMID- 22474944
TI  - Chemical and bioactivity evaluation of the bark of Neonauclea purpurea.
AB  - Bioassay-guided fractionation of the MeOH extract from the stem bark of
      Neonauclea purpurea used in traditional medicine, resulted in the isolation of 2
      indole alkaloids, cadambine (1) and alpha-dihydrocadambine (2), as well as a
      quinolic compound, 2,6-dimethoxy-1,4-benzoquinone (3). Antimalarial activity
      evaluation showed that compounds 2 and 3 exhibited mild in vitro antimalarial
      activity against Plasmodium falciparum, the chloroquine-resistant strain K1 with
      IC50 values of 6.6 and 11.3 microM, respectively. Compounds 1 and 2 showed no
      cytotoxicity to monkey (Vero) cells, but compound 3 showed weak cytotoxicity with
      an IC50 value of 1.19 microM.

PMID- 22474945
TI  - Antifeedants from Chinese medicinal herb, Erythrina variegata var. orientalis,
      against maize weevil Sitophilus zeamais.
AB  - The screening for insecticidal principles from several Chinese medicinal herbs
      showed that the stem bark of Erythrina variegata var. orientalis possessed
      significant feeding deterrence against maize weevils, Sitophilus zeamais.
      Bioassay-directed fractionation of the stem bark extract of E. variegata var.
      orientalis resulted in the isolation of two alkaloids, identified as erysopine
      and erysovine from their spectroscopic data. Erysopine and erysovine possessed
      antifeedant activity against S. zeamais adults with EC50 values of 108.5 and 89.7
      ppm, respectively.

PMID- 22474946
TI  - Kaempferol tri- and tetraglycosides from the flowers of Clematis cultivar.
AB  - A new kaempferol glycoside, kaempferol 3-O-alpha-rhamnopyranosyl-(1 --> 2)-[alpha
      rhamnopyranosyl-(1 --> 6)-beta-glucopyranoside]-7-O-beta-glucopyranoside (2) was
      isolated from the flowers of Clematis cultivar "Jackmanii Superba", together with
      a known kaempferol 3-O-alpha-rhamnopyranosyl-(1 --> 6)-beta-glucopyranoside-7-O
      beta-glucopyranoside (1). The chemical structures of the isolated glycosides were
      established by UV, LC-MS, characterization of acid hydrolysates, and 1H and 13C
      NMR spectroscopy.

PMID- 22474947
TI  - Flowers from Kalanchoe pinnata are a rich source of T cell-suppressive
      flavonoids.
AB  - The chemical composition and immunosuppressive potential of the flowers from
      Kalanchoe pinnata (Crassulaceae) were investigated. We found that the aqueous
      flower extract was more active than the leaf extract in inhibiting murine T cell
      mitogenesis in vitro. Flavonoids isolated from the flower extract were identified
      and quantitated based on NMR and HPLC-DAD-MS analysis, respectively. Along with
      quercetin, four quercetin glycosyl conjugates were obtained, including quercetin
      3-O-beta-D-glucuronopyranoside and quercetin 3-O-beta-D-glucopyranoside, which
      are described for the first time in K. pinnata. All flavonoids inhibited murine T
      cell mitogenesis and IL-2 and IL-4 production without cell toxicity. This is the
      first report on the pharmacological activity of flowers of a Kalanchoe species,
      which are not used for curative purposes. Our findings show that K. pinnata
      flowers are a rich source of T-suppressive flavonoids that may be therapeutically
      useful against inflammatory diseases.

PMID- 22474948
TI  - Novel flavanes from Livistona halongensis.
AB  - A study of the chemical constituents of a methanolic extract of the roots of
      Livistona halongensis (Arecaceae) led to the isolation of two new flavanes, 2S,3S
      3,5,7,3'-tetrahydroxy-5'-methoxyflavane (1) and 3,7,3'-trihydroxy-5'
      methoxyflavane 5-O-beta-glucopyranoside (2), together with trans-3,5,3',5'
      tetrahydroxy-4-methoxystilbene, saccharose and beta-sitosterol-3-O-beta
      glucopyranoside. The structures of these compounds were elucidated on the basis
      of spectroscopic data.

PMID- 22474949
TI  - Chemical profiling of constituents of Smilacis glabrae using ultra-high pressure
      liquid chromatography coupled with LTQ Orbitrap mass spectrometry.
AB  - A reliable LC-MS method has been applied for the separation and identification of
      major constituents of the rhizome of Smilacis glabrae. Identification of the
      constituents was carried out by interpretation of their retention time, and MS
      and MS/MS data, especially by comparing these with Sarcandra glabra under the
      same LC-MS conditions, as well as the data provided by the literature. Thirty
      three compounds, including catechin derivatives, flavanonols, phenolic acid
      derivatives and phenylpropanoid glycosides were either identified or tentatively
      characterized. Among them, compound 12 was deduced to be a new phenylpropanoid
      substituted catechin. Fragmentation behaviors of the three major categories of
      compounds were also investigated. This UPLC-PDA/ESI-MS(n) method was effective
      for the separation and identification of the constituents and could be the basis
      for the comprehensive quality control of Smilacis glabrae.

PMID- 22474950
TI  - Phenolic constituents from the heartwood of Artocapus altilis and their
      tyrosinase inhibitory activity.
AB  - From the MeOH extract of the heartwood of Artocapus altilis, thirteen phenolic
      compounds have been isolated, namely curcumin (1), desmethoxycurcumin (2),
      retrodihydrochalcone (3), apigenin (4), tangeretin (5), nobiletin (6), O
      methyldehydrodieugenol (7), dehydrodieugenol (8), beta-hydroxypropiovanillone
      (9), p-coumaric acid (10), p-hydroxybenzaldehyde (11), vanillin (12), and
      vanillic acid (13). This is the first report on the presence of these compounds
      in the heartwood of A. altilis. Compounds 1, 2, and 10 showed more potent
      tyrosinase inhibitory activities, with IC50 values ranging from 2.3 to 42.0
      microM, than the positive control kojic acid (IC50, 44.6 microM). The most active
      compound, p-coumaric acid (10) (IC50, 2.3 microM), was 22 times more active in
      tyrosinase inhibitory activity than kojic acid.

PMID- 22474951
TI  - Chemical constituents of two sages with free radical scavenging activity.
AB  - From the aerial parts of Salvia trichoclada Bentham and S. verticillata L. one
      new and two known phenolic acids, 3-(3',4'-dihydroxyphenyl)-2-hydroxymethyl
      propionic acid (1), 3-(3',4'-dihydroxyphenyl) lactic acid (2), and rosmarinic
      acid (3); two flavonoids, apigenin 4'-methyl ether 7-O-glucuronide (4), and
      luteolin 7-O-beta glucuronide (5); two lupan type triterpene aglycones, lupeol
      (6), and 30-hydroxylup-20 (29)-en-3-on (7); an oleanane-type triterpene acid,
      oleanolic acid (8); and an ursan-type triterpene acid, ursolic acid (9) were
      isolated. The structures of the compounds were elucidated by spectroscopic
      analysis. Different extracts of the plants were examined for their free radical
      scavenging activities by DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Some of the
      polar extracts showed high free radical scavenging activity.

PMID- 22474952
TI  - Synthesis of uliginosins A and B.
AB  - The uliginosins have potentially very useful biological activity, but their
      availability from natural sources is limited. Moreover, the one synthesis can not
      be reproduced. Here we report reproducible conditions for the synthesis of the
      uliginosins.

PMID- 22474953
TI  - Eucleanal: a new napthalene derivative from Euclea divinorum.
AB  - A new naphthalene derivative, named eucleanal (1), was isolated from Euclea
      divinorum Hiern., and its structure elucidated by detailed spectroscopic (1H, 13C
      NMR, COSY, HMQC, HMBC) and HREIMS analysis.

PMID- 22474954
TI  - A double-blind, randomized, clinical trial on the antileishmanial activity of a
      Morinda citrifolia (Noni) stem extract and its major constituents.
AB  - A controlled study was conducted to determine the efficiency of a topical
      ointment prepared from the stem extract of Morinda citrifolia against cutaneous
      leishmaniasis. Similarly, the in vitro antileishmanial activity of morindicone
      and morinthone isolated from the extract were investigated against Leishmania
      major. These compounds displayed good activity. Out of 40 patients, 50% showed an
      excellent response and 30% exhibited good improvement.

PMID- 22474955
TI  - Biotransformation of gambogenic acid by Chaetomium globosum CICC 2445.
AB  - Microbial transformation of gambogenic acid (1), a caged polyprenylated xanthone
      isolated from the resin of Garcinia hanburyi, was carried out with Chaetomium
      globosum CICC 2445, after screening forty-six strains of filamentous fungi. A new
      caged polyprenylated xanthone, 16,17-dihydroxygambogenic acid (2), was
      specifically obtained, as a result of hydroxylation at C-16, and C-17. Its
      structure was elucidated on the basis of spectroscopic methods. The cytotoxicity
      of compounds 1 and 2 against HeLa tumor cell line was evaluated, with both of
      them being modestly active.

PMID- 22474956
TI  - Between species diversity of Hypericum perforatum and H. maculatum by the content
      of bioactive compounds.
AB  - The objective of present study was to establish and compare the contents of
      secondary metabolites of two Hypericum species, H. perforatum and H. maculatum,
      native to Lithuania, and to evaluate factors predetermining their variation with
      some practical implications for utilization and conservation. The HPLC analysis
      of the ethanolic extracts of the studied species showed some regularity in their
      composition. Both species contained chlorogenic acid, hyperoside, quercitrin,
      quercetin and hypericin. The presence of rutin and hyperforin was observed only
      in H. perforatum. The quantitative analysis showed higher content of quercitrin
      in H. perforatum, than in H. maculatum, whereas the differences in the contents
      of quercetin, hypericin and chlorogenic acid were not statistically significant
      between the species. H. maculatum contained a significantly higher content of
      hyperoside than H. perforatum. The data on phytochemical analysis suggest almost
      equivalent use of both H. perforatum and H. maculatum extracts in the food
      industry, cosmetics and pharmaceutics.

PMID- 22474957
TI  - Total phenolic content and antioxidant activity of Salvia spp. exudates.
AB  - The total phenolic content and antioxidant activity of 6 Salvia spp. exudates
      were measured to find new potential sources of natural antioxidants. Total
      phenolic content was assessed by a modified Prussian blue method, and the
      antioxidant activity by two methods: 1,1-diphenyl-2-picryl-hydrazyl (DPPH)
      radical scavenging capacity assay and lipoxygenase inhibitory assay. The total
      phenolic content ranged between 1.3 microg/mg DW (S. fallax) and 74.0 microg/mg
      DW (S. cacaliaefolia). In the DPPH test, S. cacaliaefolia was more effective than
      BHT, while in the inhibition of lipid peroxidation all the extracts presented
      good antioxidant capacity.

PMID- 22474958
TI  - An efficient microwave assisted extraction of phenolic compounds and antioxidant
      potential of Ginkgo biloba.
AB  - Flavonoid glycosides are a significant group of compounds found in Ginkgo biloba
      leaves, but the long extraction procedures in existing methods are a challenging
      problem. In this work, a microwave-assisted extraction (MAE) method has been
      developed for extracting bioactive compounds from G. biloba. Several variables
      were optimized, such as extracting solvent, microwave power, and extraction time
      that can potentially affect the extraction yield. The total phenolic content,
      antioxidant activity (using DPPH, ABTS and FRAP assays) and flavonoid glycosides
      of different extracts using RP-HPLC were assessed. The antioxidant capacity was
      found to be highest with MAE using 60% aq. ethanol as extracting solvent and
      microwave power of 120W for 20 min.

PMID- 22474959
TI  - Synthesis and anti-tumor activity evaluation of rhein-aloe emodin hybrid
      molecule.
AB  - To improve the anti-tumor effects of rhein and aloe-emodin, a rhein-aloe-emodin
      hybrid molecule (RH-AE) was synthesized from rhein and aloe-emodin in the
      presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP).
      Chemical and spectroscopic methods, such as 1H and 13C NMR spectroscopy, and HR
      ESIMS were used for the structure identification of RH-AE. Using the cell
      counting kit-8 (CCK-8) assay, the in vitro anti-tumor effects were compared
      between RH-AE, rhein and aloe-emodin on human hepatoma HepG2, human
      nasopharyngeal carcinoma CNE, human lung cancer NCI-H460, human ovarian cancer SK
      OV-3, and human cervical cancer Hela cells. The results showed that the half
      inhibitory concentration (IC50) of RH-AE on HepG2, CNE, NCI-H460, SK-OV-3, and
      Hela cells were significantly lower than those of rhein and aloe-emodin. This
      showed that RH-AE has a better in vitro anti-tumor effect than rhein and aloe
      emodin.

PMID- 22474960
TI  - A new peptide isolated from a marine derived Streptomyces bacillaris.
AB  - A new peptide, L-O-Lac-L-Val-D-O-Hiv-D-Val (1), consisting of D-valine, L-valine,
      L-lactic acid, and 3-D-hydroxyisovaleric acid, was isolated from the culture of
      the marine sediment derived Streptomyces bacillaris. The planar structure of
      compound 1 was assigned by 1D, 2D NMR and mass spectroscopic analyses. Following
      acid and base hydrolysis, the absolute configuration of the valine residues in 1
      were determined by application of the advanced Marfey's method and the absolute
      configurations of hydroxy acids units were determined by a HPLC method based on
      Mosher's reagents.

PMID- 22474961
TI  - Biological activity and tissue specific accumulation of fluorescently labeled
      methyl jasmonate.
AB  - The C-7 position of jasmonate is practical for synthesis of a probe to use for
      chemical biological studies. To confirm the utility, we synthesized fluorescent
      labeled methyl jasmonate. The synthesized compound exhibited Arabidopsis thaliana
      root growth inhibitory and meandering activity, and potent fluorescence was
      observed inside the root and root hairs.

PMID- 22474962
TI  - A new resin glycoside from Ipomoea maxima.
AB  - A new resin glycoside (1) was isolated from the aerial part of Ipomoea maxima,
      together with three known compounds, pescaprein XX (2), stoloniferin X (3), and
      stoloniferin IX (4). The structure of 1 was elucidated on the basis of 1D NMR
      spectroscopy, a fragmentation study by APCIMS, and HRESIMS analysis.

PMID- 22474963
TI  - Hypoglycemic constituents of Gynura divaricata subsp. formosana.
AB  - Gynura divaricata Kitam. subsp. formosana is a folk medicine used as a
      hypoglycemic agent for diabetes patients in Taiwan. Guided by the hexose
      transport assay, the hypoglycemic constituents of the aerial part of this plant
      were disclosed through chromatographic methods. They are fructooligosaccharides,
      including beta-D-fructofuranose, sucrose, 1-kestose, nystose, and 1(F)-beta
      fructofuranosylnystose. The hexose transport assay indicated that nystose was the
      most potent among these compounds, showing a 46.7% difference from pinitol in the
      stimulation index at a concentration of 0.5 mg/mL.

PMID- 22474964
TI  - Constituents of south Indian vetiver oils.
AB  - The essential oils isolated from vetiver [Vetiveria zizanioides (L.) Nash.] roots
      collected from four locations in south India were analyzed by GC-FID and GC-MS.
      Eighty constituents, representing 94.5-97.8% of the oils, have been identified.
      The oils from Bangalore, Hyderabad, Kundapur, and Mettupalayam were rich in
      sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane,
      eremophilane, and zizaane skeletons. The main components of the four essential
      oils were: eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9-6.1%), beta
      vetivenene (0.9-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10
      ol (5.0-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita
      4(15),7(11)-dien-12-ol (3.7-5.9%), eremophila-1 (10),11-dien-2alpha-ol
      (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1-19.2%), and eremophila
      1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol
      (isovalencenol) (5.6-6.9%). The important compounds that impart the
      characteristic vetiver odor are: khusimene, delta-selinene, beta-vetivenene,
      cyclocopacamphan-12-ol (epimers A and B), vetiselinenol, khusimol, isovalencenol,
      khusimone, alpha-vetivone, and beta-vetivone. The chemical profiles of the oils
      are comparable to Haitian vetiver oil.

PMID- 22474965
TI  - Composition of seed essential oils of Rhododendron tomentosum.
AB  - For the first time, the chemical composition of the seed essential oil of
      Rhododendron tomentosum was determined. Forty-seven compounds were identified,
      comprising 91.7% of the total oil. Palustrol (38.3%) and ledol (27.0%) were the
      predominant constituents. Some constituents, such as beta-pinene oxide, iso
      menthyl acetate, nerolidyl acetate, cadalene and guaiazulene were characteristic
      only for the seeds and were identified for the first time in Rh. tomentosum oils.
      For comparison purposes, the essential oil isolated from the shoots of the same
      plant were analyzed [GC(FID) in combination with RIs, GC-MS and 13C NMR]. More
      than a half of the oil was comprised of ledol (36.5%) and palustrol (21.0%).
      Quantitative analysis of ascaridol, a heat-sensitive compound, was carried out by
      13C NMR spectroscopy. Indeed, ascaridol undergoes partial thermal isomerization
      to iso-ascaridol during GC analyses.

PMID- 22474966
TI  - The leaf essential oils of five Vietnamese Desmos species (Annonaceae).
AB  - The leaf essential oils of five Desmos species from Vietnam have been extracted
      by steam distillation and subjected to GC and GC-MS analyses. The plant samples
      were Desmos cochinchinensis Lour., D. penduculosus (A. DC.) Ban, D. penducolosus
      var. tonkinensis Ban, D. chinensis Lour., and D. dumosus (Roxb.) Saff. The oils
      were rich in sesquiterpene hydrocarbons (65.9%-88.9%) and monoterpene
      hydrocarbons (6.3%-30.9%). The oxygenated counterparts were less common. The
      quantitatively significant constituents of the oils were alpha-pinene (2.4%
      12.1%), beta-elemene (2.2-39.5%), beta-caryophyllene (13.9-26.3%), germacrene D
      (9.9-15.5%), bicyclogermacrene (2.0-11.4%) and alpha-humulene (3.8-7.5%). The
      studied oils could be classified into two chemical forms: oils with abundance of
      beta-caryophyllene, germacrene D and alpha-pinene (D. cochinchinensis, D.
      penducolosus var. tonkinensis, D. chinensis and D. Dumosus) and oil with high
      amounts of beta-elemene, beta-caryophyllene and germacrene D (D. penduculosus).

PMID- 22474967
TI  - Essential oil composition of Cachrys cristata--a rare and endangered species in
      the flora of Serbia.
AB  - Cachrys cristata DC. (Apiaceace) is a rare and critically endangered species in
      the flora of Serbia. Essential oil isolated by hydrodistillation from the aerial
      parts and fruits of this species was analyzed using combined GC and GC/MS. The
      oil from the aerial parts was rich in sesquiterpenes (45.7%) and oxygenated
      sesquiterpenes (32.9%), while the fruit oil consisted of a higher percentage of
      sesquiterpenes (48.3%) and oxygenated sesquiterpenes (36.7%). The dominant
      constituents in the oil from aerial parts were phytol (13.1%) and germacrene D
      (12.9%), while in the fruit oil suberosin (19.7%) and germacrene D (12.3%) were
      the most abundant.

PMID- 22474968
TI  - Volatiles from Magnolia grandiflora flowers: comparative analysis by simultaneous
      distillation-extraction and solid phase microextraction.
AB  - The composition of the volatile compounds isolated by simultaneous distillation
      extraction (SDE) and headspace-solid phase microextraction (SPME) from flowers of
      Magnolia grandiflora growing in Cuba was investigated by GC/FID and GC/MS. Sixty
      seven and thirty-four components were obtained by SDE and SPME, respectively.
      beta-Pinene (10.5%), geraniol (7.4%) and germacrene D (6.2%) were the main
      constituents of the volatile oil isolated by SDE, while (E)-beta-ocimene (24.6%),
      geraniol (18.9%), beta-elemene (11.2%) and germacrene D (9.9%) were the most
      abundant in the headspace of the flowers, respectively.

PMID- 22474969
TI  - Essential oil composition, cytotoxic and antibacterial activities of five
      Etlingera species from Borneo.
AB  - Essential oils obtained by hydrodistillation from the rhizomes of Etlingera
      pyramidosphaera (K. Schum.) R. M. Sm, E. megalocheilos (Griff.) A.D. Poulsen,
      comb. nov., E. coccinea (Blume) S. Sakai & Nagam, E. elatior (Jack) R. M. Sm, and
      E. brevilabrum (Valeton) R. M. Sm were analyzed by GCMS. The highest oil yield
      was obtained from E. pyramidosphaera (0.45%), followed by E. elatior (0.38%), E.
      coccinea (0.30%), E. brevilabrum (0.28%) and E. megalocheilos (0.25%). The major
      constituents of the essential oils were oxygenated monoterpenes, followed by
      sesquiterpenes, oxygenated sesquiterpenes, oxygenated diterpenes and diterpenes.
      The essential oils from E. pyramidosphaera and E. brevilabrum exhibited the best
      cytotoxicity against MCF 7 (LC50: 7.5 +/- 0.5 mg mL(-1)) and HL 60 (LC50: 5.0 mg
      mL(-1)), respectively. Strong inhibition was also observed for the essential oils
      of E. coccinea and E. megalocheilos against Staphylococcus aureus (MIC: 8.0 +/-
      0.5 mg mL(-1), and 5.0 +/- 0.5 mg mL(-1)) and Streptococcus pyrogenes (MIC: 6.0
      +/- 0.5 mg mL(-1) and 8.0 +/- 0.5 mg mL(-1)).

PMID- 22474970
TI  - Essential oil composition and antibacterial activity of Monticalia greenmaniana
      (Asteraceae).
AB  - The essential oils from fresh aerial parts of Monticalia greenmaniana (Hieron) C.
      Jeffrey (Asteraceae) collected in March, were analyzed by GC/MS. Oil yields (w/v)
      of 0.1% (flowers), 0.07%, (stems) and 0.1% (leaves) were obtained by
      hydrodistillation. Thirteen, sixteen and eighteen components, respectively, were
      identified by comparison of their mass spectra with those in the Wiley GC-MS
      Library data base. The major components of the flower and stem oils were 1-nonane
      (38.8% flowers; 33.5% stems), alpha-pinene (29.0% flowers; 14.8% stems) and
      germacrene D (15.6% flowers; 18.6% stems). However, in the leaf oil, germacrene D
      was observed at 50.7%, followed by beta-cedrene at 8.4%. The leaf essential oil
      showed a broad spectrum of antibacterial activity against the important human
      pathogenic Gram-positive and Gram-negative bacteria Staphylococcus aureus (ATCC
      25923), Enterococcus faecalis (ATCC 19433), Escherichia coli (ATCC 25922),
      Pseudomonas aeruginosa (ATCC 27853) and Klebsiella pneumoniae (ATCC 25955) with
      MIC values ranging from 75 to 6000 ppm.

PMID- 22474971
TI  - Bioactivity of the essential oil of an argentine collection of Acanthospermum
      hispidum (Asteraceae).
AB  - The essential oil of an Argentine collection of the annual herb Acanthospermum
      hispidum DC. (Asteraceae), which contains the sesquiterpenoids beta-caryophyllene
      (35.2%), alpha-bisabolol (11.4%), and germacrene D (11.1%) as major constituents,
      displayed molluscicidal effects on an adult population of Biomphalaria peregrina
      Orbigny (LD50 37.8 microg/mL) and produced alteration of the feeding and
      oviposition behavior of the polyphagous insect Spodoptera frugiperda Smith when
      incorporated in the larval diet at 250 microg/g. In addition, a selective
      antibacterial activity was observed against pathogenic strains of Staphylococcus
      aureus and Enterococcus faecalis (MICs 62.5 and 125 microg/mL), but was inactive
      at 125 microg/mL against three beneficial lactic acid bacteria. Synergistic
      interactions were further validated by FIC index determination of the combination
      of the antibiotics oxacillin and gentamicin and the essential oil on the four
      pathogenic strains evaluated.

PMID- 22474972
TI  - Antibacterial activity and comparison of the volatile constituents obtained by
      several extraction methods from the flowers, stems and leaves of Astrodaucus
      orientalis.
AB  - The oils of the flowers, stems and leaves of Astrodaucus orientalis L. were
      separately extracted using hydrodistillation (HD), head-space solid-phase
      microextraction (HS-SPME) and microwave assisted head-space solid-phase
      microextraction (MA-HS-SPME). The volatile constituents were analyzed by GC and
      GC/MS. Temperature and time of extraction, microwave power and exposure time of
      extraction were optimized. Polydimethylsiloxane (PDMS) fiber was used as the
      solid phase for SPME methods. The main constituents of the flower, stem and leaf
      oils isolated by HD, HS-SPME and MA-HS-SPME are as follows, respectively: beta
      pinene (20.5%, 13.9% and 30.4%), alpha-thujene (8.7%, 16.2% and 10.9%) and alpha
      pinene (7.6%, 14.3% and 10.9%) for the flowers, sabinene (11.8%, 32.3% and
      11.8%), alpha-pinene (8.7%, 28.8% and 6.1%) and p-mycrene (2.5%, 12% and 8.5%)
      for the stem, and alpha-pinene (9.4%, 37.1% and 22.5%), sabinene (13.5%, 26.3%
      and 23.5%), beta-pinene (6.3%, 9.8% and 10%) and p-mycrene (3.2%, 2.5% and 15.6%)
      for the leaf. The minimum inhibitory concentrations (MIC) were determined for all
      essential oils obtained by HD against both Gram-positive (Bacillus subtilis) and
      Gram-negative (Escherichia coli) bacteria using the agar dilution method. These
      oils showed the good activities against the both bacteria (0.5 - 1.5 mg/mL).

PMID- 22474973
TI  - In vitro inhibitory activity of essential oil vapors against Ascosphaera apis.
AB  - This work evaluates the in vitro inhibitory activity of 70 essential oils (EOs)
      in the vapor phase for the control of Chalkbrood disease caused by Ascosphaera
      apis Maassen ex Claussen (Olive et Spiltoir). Two wild strains isolated from
      infected honey bee colonies together with one standard collection strain were
      tested by the microatmosphere method. From 70 EOs, 39 exhibited an antifungal
      effect against A. apis standard and wild strains. The greatest antifungal action
      was observed for EO vapors from Armoracia rusticana, followed by Thymus vulgaris,
      Cymbopogon flexosus, Origanum vulgare and Allium sativum. An investigation of
      chemical composition by GC-MS revealed, that the most active EOs contained allyl
      isothiocyanate, citral, carvacrol and diallyl sulfides as the main constituents.
      The chemical composition plays a key role, as activities of different EOs from
      the same botanical species were different according to their composition.

PMID- 22474974
TI  - Chemical composition and biological activity of essential oil from Pulicaria
      undulata from Yemen.
AB  - The chemical composition of the essential oil obtained from the leaves of
      Pulicaria undulata Gamal Ed Din (syn P. orientalis sensu Schwartz and P.
      jaubertii Gamal Ed Din) was analyzed by GC-MS. Major compounds of P. undulata oil
      were the oxygenated monoterpenenes, carvotanacetone (91.4%) and 2,5-dimethoxy-p
      cymene (2.6.%). The antimicrobial activity of the essential oil was evaluated
      against six microorganisms, Escherichia coli Pseudomonas aeruginosa,
      Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and
      Candida albicans, using disc diffusion and broth microdilution methods. The oil
      showed the strongest bactericidal activity against Staphylococcus aureus and
      methicillin-resistant S. aureus, as well as Candida albicans. The essential oil
      showed moderate cytotoxic activity against MCF-7 breast tumor cells, with an IC50
      of 64.6 +/- 13.7 microg/mL. Bioautographic assays were used to evaluate the
      acetylcholinesterase inhibitory effect as well as antifungal activity of the oil
      against Cladosporium cucumerinum.

PMID- 22474975
TI  - Composition, antioxidant, antimicrobial and anti-wood-decay fungal activities of
      the twig essential oil of Taiwania cryptomerioides from Taiwan.
AB  - This study investigated the chemical composition, antioxidant, antimicrobial and
      anti-wood-decay fungal activities of the essential oil isolated from the twigs of
      Taiwania cryptomerioides from Taiwan. The essential oil was isolated using
      hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and
      GC-MS. A total of 35 compounds were identified, representing 100% of the oil. The
      main components identified were alpha-cadinol (45.9%), ferruginol (18.9%) and
      beta-eudesmol (10.8%). The antioxidant activity of the oil was tested by the DPPH
      (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging capability test. The
      results showed an IC50 of 90.8 +/- 0.2 microg/mL. The active source compound was
      ferruginol. The antimicrobial activity of the oil was tested by the disc
      diffusion and micro-broth dilution methods against ten microbial species. The oil
      exhibited strong growth suppression against Gram-positive bacteria and yeast with
      inhibition zones of 45-52 mm and MIC values of 31.25-62.5 microg/mL,
      respectively. The anti-wood-decay fungal activity of the oil was also evaluated.
      The oil demonstrated excellent activity against four wood-decay-fungal species.
      For the antimicrobial and anti-wood-decay fungal activities of the oil, the
      active source compounds were determined to be alpha-cadinol, beta-eudesmol and
      ferruginol.

PMID- 22474976
TI  - Essential oil from the leaves of Annona vepretorum: chemical composition and
      bioactivity.
AB  - The essential oil from the leaves of Annona vepretorun was obtained by
      hydrodistillation using a Clevenger-type apparatus and analyzed by GC-MS and GC
      FID. Eighteen compounds representing 98.1% of the crude essential oil were
      identified. The major compounds identified were bicyclogermacrene (43.7%),
      spathulenol (11.4%), alpha-felandrene (10.0%), alpha-pinene (7.1%), (E)-beta
      ocimene (6.8%), germacrene D (5.8%), and p-cymene (4.2%). The trypanocidal
      activity against Trypanosoma cruzi epimastigote forms, as well as, the
      antimicrobial and antioxidant proprieties was investigated. The essential oil
      showed a potent trypanocidal activity with IC50 value of 31.9 +/-1.3 microg x mL(
      1). For antimicrobial activity, the best result was observed against Candida
      tropicalis with a MIC value of 100 microg x mL(-1). For antioxidant capacity the
      essential oil showed weak activity.

PMID- 22474977
TI  - Chemical composition and insecticidal activity of the essential oil of Artemisia
      eriopoda against maize weevil, Sitophilus zeamais.
AB  - In our screening program for new agrochemicals from local wild plants, Artemisia
      eriopoda was found to possess insecticidal activities against the maize weevil,
      Sitophilus zeamais. The essential oil of the aerial parts of A. eriopoda was
      obtained by hydrodistillation and investigated by GC and GC-MS. The main
      components of the essential oil are germacrene D (21.6%) and eucalyptol (14.2%).
      The essential oil possesses fumigant toxicity against S. zeamais adults with a
      LC50 value of 11.5 mg/L air and also shows contact toxicity against S. zeamais
      adults with a LD50 value of 24.8 microg/adult, respectively.

PMID- 22474978
TI  - The chemical composition of the essential oils of Cirsium palustre and C.
      rivulare and their antiproliferative effect.
AB  - The composition of the essential oils of Cirsium palustre and C. rivulare and
      their antiproliferative activity against breast adenocarcinoma cells (MCF-7 and
      MDA-MBA-231) were investigated. The essential oils obtained by hydro-distillation
      from the roots (yield 0.2 and 0.1% v/w, respectively), leaves and inflorescences
      (yield below 0.01%), were analyzed by gas chromatography coupled with mass
      spectrometry (GC-MS). The composition of the essential oils in the respective
      organs of each plant differed considerably. On the other hand, similarities were
      observed in the composition of root and leaf oils. In C. palustre and C. rivulare
      root oil, 50 and 39 constituents were identified, accounting for 95.3% and 92.4%
      of the total content. The main components were aplotaxene and its derivatives,
      representing 78.6% and 46.6% of the total content. In leaf oils of both species,
      59 and 49 compounds, respectively, were identified, representing 67.4% and 78.3%
      of the total content. The major constituents were beta-damascenone (4.1% and
      13.4%, respectively) and beta-ionone (6.7% and 5.3%, respectively). Short-chain
      saturated and unsaturated aliphatic alcohols and aldehydes constituted another
      important group of compounds (17.7% and 9.0%, respectively). The essential oils
      of the roots have moderate anti-proliferative activity, with IC50 values ranging
      from 110 to 140 microg/mL. These concentrations were below the level able to
      inhibit the proliferation of healthy cells.

PMID- 22474979
TI  - Phytotherapy of alcoholism.
AB  - Alcoholism is a medical, social, and economic problem where treatment methods
      mostly include difficult and long-lasting psychotherapy and, in some cases, quite
      controversial pharmacological approaches. A number of medicinal plants and pure
      natural compounds are reported to have preventive and therapeutic effects on
      alcoholism and alcohol dependency, but their constituents, efficacy and mechanism
      of action are mostly unknown so far. Recently, kudzu [Pueraria lobata (Willd.)
      Ohwi], St. John's wort (Hypericum perforatum L.), danshen (Salvia miltiorrhiza
      Bge.), ginseng (Panax ginseng C.A. Mey.), Japanese raisin tree (Hovenia dulcis
      Thunb.), ibogaine (Tabernanthe iboga H. Bn.), evening primrose (Oenothera biennis
      L.), prickly pear fruit (Opuntia ficus indica (L.) Mill.), purple passionflower
      (Passiflora incarnata L.), thyme (Thymus vulgaris L.), fenugreek seed (Trigonella
      foenum-graecum L.), ginger (Zingiber officinale Roscoe) and many others drew the
      attention of researchers. Can, therefore, drugs of natural origin be helpful in
      the treatment of alcoholism or in decreasing alcohol consumption?

PMID- 22474980
TI  - [Inhibitory effect of CMTM5 on xenografted human prostatic cancer in nude mice].
AB  - OBJECTIVE: To investigate the inhibitory effect of CKLF-like MARVEL transmembrane
      domain containing 5 (CMTM5) on xenografted human prostatic cancer in nude mice
      and its action mechanism. METHODS: We established a model of xenografted
      prostatic cancer by inoculating PC-3 cells subcutaneously into nude mice, and 3
      weeks later injected CMTM5 adenovirus locally into the tumor followed by daily
      observation of the tumor volume and body weight of the experimental animals. All
      the rats were killed 2 weeks after CMTM5 injection and the tumor tissue harvested
      for detection of the inhibitory effect of CMTM5 on the expressions of VEGF and NF
      kappaB proteins by immunohistochemistry. RESULTS: The tumor volume was
      significantly smaller and body weight of the CMTM5-treated mice were (573.39 +/-
      175.24) mm3 and (0.55 +/- 0.11) g, respectively, significantly decreased as
      compared with those of the controls ([1482.50 +/- 327.86] mm3 and [1.31 +/- 0.29]
      g) (P = 0.03 and P = 0.027). Immunohistochemistry showed that the expressions of
      VEGF and NF-kappaB were obviously down-regulated in the CMTM5 group in comparison
      with the control group. CONCLUSION: CMTM5 suppresses the growth of prostate
      cancer by down-regulating the expressions of VEGF and NF-kappaB.

PMID- 22474981
TI  - [AIDS-related knowledge among adult males in Chongqing City].
AB  - OBJECTIVE: To evaluate AIDS-related knowledge among adult men in Chongqing City,
      and provide some evidence for AIDS-related health education. METHODS: Using the
      randomized multistage stratified cluster sampling method, we investigated AIDS
      related knowledge among the adult males in Chongqing City. RESULTS: Of the 1502
      adult men, those who knew the three major transmitting routes of AIDS (blood
      borne, vertical transmission and sexual contact) constituted 85.35, 83.16 and
      66.11%, respectively, and 22.70% did not know the proper use of condoms. Those
      who thought that AIDS could be transmitted by mosquito bite, kissing, dining
      together, handshake or embracing made up 54.86, 50.6, 30.29 and 19.11%,
      respectively. The floating population scored significantly lower than the
      resident population in total AIDS knowledge, HIV transmission knowledge and HIV
      non-transmission knowledge (P<0.01). CONCLUSION: AIDS-related knowledge among the
      adult men in Chongqing City needs to be improved by enhancing targeted AIDS
      related health education.

PMID- 22474982
TI  - [Expressions of BNP and NPR-A in rat models of chronic nonbacterial prostatitis
      and their significance].
AB  - OBJECTIVE: To investigate the expressions of brain natriuretic peptide (BNP) and
      natriuretic peptide receptor (NPR-A) in the cord dorsal horn ganglion (DRG) of
      rat models of chronic nonbacterial prostatitis (CNP) and the relation of BNP and
      NPR-A with CNP-induced chronic pain. METHODS: We established CNP models in 30
      healthy clean SD rats using Freund's complete adjuvant, and included another 10
      in a sham-operation group. The prostate tissues were subjected to HE staining,
      and the expressions of BNP and NPR-A in the L5-S2 DRGs were detected by real-time
      PCR. RESULTS: Higher degree of inflammation was related to longer modeling time.
      At 3, 7 and 10 days, the expressions of BNP in the CNP models were 2.16 +/- 0.35,
      1.61 +/- 0.21 and 1.32 +/- 0.36, and those of NPR-A were 2.75 +/- 0.06, 2.15 +/-
      0.15 and 1.04 +/- 0.13, respectively, significantly higher at 3 and 7 days as
      compared with the sham-operation group (P<0.05), but with no statistically
      significant difference at 10 days. CONCLUSION: BNP and NPR-A are expressed in the
      L5-S2 DRGs of SD rats and their expressions can be upregulated by CNP. BNP and
      NPR-A may be involved in the mechanisms of CNP-induced pain.

PMID- 22474983
TI  - [Correlation of histological prostatitis with PSA, prostate volume, PSAD, IPSS,
      Qmax and PVR in BPH patients].
AB  - OBJECTIVE: To explore the correlation of histologically proven prostatitis with
      the level of prostate specific antigen (PSA), prostate volume, PSA density
      (PSAD), international prostate symptom score (IPSS), maximum flow rate (Qmax) and
      post-void residual volume (PVR) in men with symptoms of benign prostate
      hyperplasia (BPH). METHODS: Totally 673 patients surgically treated for BPH were
      divided into Groups A and B in accordance with histological findings, the former
      including those with histological prostatitis, and the latter without it.
      Comparisons were made between the two groups in the PSA level, prostate volume,
      PSAD, IPSS, Qmax and PVR. RESULTS: The PSA level, prostate volume, IPSS and PVR
      were significantly higher in Group A ([5.64 +/- 2.48] microg/L, [43.66 +/- 13.11]
      ml, 24.72 +/- 5.39 and [124.90 +/- 49.80] ml) than in B ([4.97 +/- 1.99]
      microg/L, [40.41 +/- 11.44] ml, 23.40 +/- 6.21 and [112.73 +/- 50.03] ml)
      (P<0.05), while Qmax markedly lower in the former ([6.94 +/- 3.23] ml/s) than in
      the latter ([7.75 +/- 3.52] ml/s) (P<0.05), but PSAD showed no statistically
      significant difference between the two groups (0.129 +/- 0.048 vs 0.123 +/-
      0.034, P>0.05). CONCLUSION: Histological prostatitis can significantly increase
      the PSA level, prostate volume, IPSS and PVR, and reduce the Qmax of the patient,
      but is not correlated with PSAD. It is an important factor influencing the
      clinical progression of BPH.

PMID- 22474984
TI  - [Predictors of depression symptoms in patients with chronic prostatitis].
AB  - OBJECTIVE: To study the predictors of depression in patients with chronic
      prostatitis (CP). METHODS: We enlisted 49 CP patients in this study, and
      evaluated their clinical symptoms with NIH-CPSI and IIEF-5, their depression
      symptoms with the Self-Rating Depression Scale (SDS) and Symptom Checklist 90
      (SCL-90), their trait-oriented coping styles with the Trait-Oriented Coping
      Styles Questionnaire (TCSQ), and their illness perceptions with the Illness
      Perception Questionnaire (IPQ-R). We conducted Pearson correlation analysis on
      the correlation of depression with the clinical symptoms of the patients and used
      multivariate Logistic regression models to analyze the predictors of their
      depression. RESULTS: Pain or discomfort, urination symptoms, impact of symptoms
      and total score in NIH showed a significant positive correlation with depression
      symptoms, but a negative correlation with erectile function (r = 0.32, 0.31,
      0.35, 0.38, and -0.36, P<0.05). Besides, 43.4% of the depression symptoms in the
      CP patients could be explained by negative trait-oriented coping and disease
      impact factors (R2 = 0.434, adjusted R2 = 0.456, F = 14.853, P<0.001).
      CONCLUSION: Depression symptoms are closely associated with clinical symptoms,
      and negative trait-oriented coping and disease impact factors are the main
      predictors of depression in CP patients.

PMID- 22474985
TI  - [Protective effect of ERbeta on penile vascular endothelium in mice].
AB  - OBJECTIVE: To investigate the protective effect of ERbeta on the penile vascular
      endothelium in mice. METHODS: We randomly selected 12 ERbeta knockout (ERbetaKO)
      and 12 C57BL/6 male mice, and divided them into four groups: normal control,
      ERbetaKO, ERbetaKO + TNFalpha, and wild-type + TNFalpha group. The former two
      were treated with normal saline, while the latter two by intraperitoneal
      injection of TNFalpha at 6 microg/(kg x d) for 14 days. Then we observed the
      spontaneous erectile response induced by APO and changes of the endothelial cells
      by immunohistochemical staining of CD34 and vWF, and detected cell apoptosis in
      the penile cavernous tissue by TUNEL. RESULTS: Compared with the normal control
      group, the ERbetaKO group showed significantly increased erectile latency
      (P<0.05), but no significant difference in the number of erections; the ERbetaKO
      + TNFalpha and wild-type + TNFalpha groups, too, exhibited remarkably longer
      erectile latency (P<0.05) but fewer erections (P<0.05), with even more obvious
      changes in the ERbetaKO + TNFalpha group. The expressions of CD34 and vWF were
      significantly reduced in the ERbetaKO group (2.25 +/- 0.50 and 2.00 +/- 0.00),
      ERbetaKO + TNFalpha group (0.25 +/- 0.50 and 0.33 +/- 0.58) and wild-type +
      TNFalpha group (1.50 +/- 0.58 and 1.25 +/- 0.50) as compared with those in the
      control (3.00 +/- 0.00 and 2.75 +/- 0.50) (P<0.05), even lower in the ERbetaKO +
      TNFalpha than in the wild-type + TNFalpha group (P<0.05). Apoptotic cells were
      found only in the ERbetaKO + TNFalpha group. CONCLUSION: After ERbeta knockout
      and especially after treated with the endothelial injury factor TNFalpha,
      endothelial cells are decreased in the penile vessels in mice, which suggests
      that ERbeta has a protective effect on the penile cavernous sinus endothelium.

PMID- 22474986
TI  - [Expression of Notch1 in the genital tubercle of male rats with hypospadias
      induced by Di-n-butyl phthalate].
AB  - OBJECTIVE: To detect the differential expression of Notch1 in the genital
      tubercle (GT) of fetal male rats with hypospadias induced by maternal exposure to
      Di-n-butyl phthalate (DBP) and that in normal control fetal rats in order to
      further explore the role of Notch1 in DBP-induced hypospadias. METHODS: Twenty
      pregnant SD rats were equally and randomly divided into an experimental and a
      control group, the former given DBP and the latter soybean oil intragastrically
      at 800 mg/(kg x d) and 2 ml/d respectively from gestation day (GD) 14 to GD 18.
      On GD 19, the birth weight (BW), anogenital distance (AGD) and hypospadias
      incidence were recorded, GTs of the fetal male rats collected, and the expression
      of Notch1 analyzed by Western blot and immunohistochemistry. RESULTS: The BW of
      the fetal male rats was (4.40 +/- 0.30) g in the experimental group,
      significantly lower than (6.11 +/- 0.40) g in the control (P <0.05), and the AGD
      was (2.17 +/- 0.18) mm in the former, markedly shorter than (3.28 +/- 0.16) mm in
      the latter (P<0.05). The incidence of hypospadias was 42.9%. The relative
      expression of Notch1 was remarkably lower in the hypospadiac rats than in the
      normal controls (0.671 +/- 0.021 vs 1.327 +/- 0.031, P<0.05), and it was mainly
      located in the epithelial cells of the GT. The staining intensity was obviously
      weaker in the hypospadias than in the normal control group. CONCLUSION: DBP has
      an obvious toxic effect on fetal male rats and can change the expression of
      Notch1 in the GT. It possibly affects cell proliferation and apoptosis and
      epithelial-to-mesenchymal transition (EMT), resulting in the occurrence of
      hypospadias.

PMID- 22474987
TI  - [Direct fumigation for freeze-thawing of human sperm: an experimental study].
AB  - OBJECTIVE: To study the effect of direct fumigation on the post-thaw recovery
      rate of cryopreserved spermatozoa, and to search for a best method for human
      sperm cryopreservation. METHODS: We collected semen samples from 100 donors
      conforming to the normal reference values in WHO Laboratory Manual for the
      Examination and Processing of Human Semen (5th Ed), divided them into two groups,
      and subjected them to cryopreservation by programmable freezing (Group A) and
      direct fumigation (Group B), respectively. We detected the progressive motility
      of pre-freezing and post-thaw sperm with a computer-assisted semen analyzer, and
      compared the effects of the two methods on the functional integrity of sperm
      membrane and the rate of abnormal sperm using the percentage of hypo-osmotic
      swelling sperm and modified Papanicolaou staining. RESULTS: Statistically
      significant differences were found in post-thaw sperm progressive motility
      between the Groups A and B ([34.0 +/- 18.4]% vs [43.0 +/- 19.5]%, P<0.05), both
      remarkably decreased as compared with pre-freezing ([57.0 +/- 16.7]%, P<0.05).
      Such differences were also found in the post-thaw recovery rate of progressively
      motile sperm between the two groups ([52.2 +/- 20.6]% vs [67.1 +/- 20.0]%,
      P<0.05). The post-thaw percentage of hypo-osmotic swelling sperm was obviously
      decreased in both Groups A and B ([67.1 +/- 11.1]% and [70.6 +/- 10.0]%) in
      comparison with pre-freezing ([84.5 +/- 7.5]%, P<0.05), with significant
      differences between A and B (P<0.05). However, the rate of sperm abnormality was
      evidently increased in Groups A and B ([85.0 +/- 8.7% and [85.7 +/- 9.1]%),
      significantly higher than pre-freezing ([77.8 +/- 9.6]%, P<0.05), but with no
      significant differences between A and B (P>0.05). CONCLUSION: Direct fumigation
      is superior to programmable freezing for its easier operation, wider application,
      and higher sperm recovery rate.

PMID- 22474988
TI  - [Testicular sperm cryopreservation for male fertility preservation].
AB  - OBJECTIVE: To investigate the effectiveness of testicular sperm cryopreservation
      in male fertility preservation by evaluating the clinical outcome of ICSI cycles
      with frozen-thawed testicular sperm for azoospermia patients. METHODS: We
      retrospectively analyzed 96 samples of cryopreserved testicular sperm obtained by
      testicular biopsy, vasovasostomy (V-V), vasoepididymostomy (V-E) , of which 55
      were subjected to 60 ICSI cycles with frozen-thawed testicular sperm. We
      evaluated the rates of sperm recovery, fertilization, cleavage, transferable and
      good-quality embryos, clinical pregnancy, pregnancy outcome, and health of the
      newborns. RESULTS: All the frozen testicular sperm samples were recovered
      successfully. The rates of fertilization, 2PN fertilization, cleavage, available
      embryos and good-quality embryos were 77.6, 69.4, 99.4, 84.5 and 40.8%,
      respectively. There were transferable embryos in all cycles. Fresh embryos were
      transferred in 52 of the 60 cycles, with the clinical pregnancy rate of 57.7%
      (30/52), including 19 singletons and 11 twins, and the rates of implantation and
      miscarriage were 38.7% (41/106) and 3.33% (1/30). Up to the present time, there
      have been 20 healthy newborns, including 12 boys and 8 girls, and another 13
      ongoing pregnancies. No birth defects have been found so far. CONCLUSION:
      Desirable clinical outcomes can be obtained from ICSI cycles with frozen-thawed
      testicular sperm, and testicular sperm cryopreservation is an effective method of
      fertility preservation for azoospermia males.

PMID- 22474989
TI  - [Internal quality control of sperm concentrations in semen analysis:
      establishment of a method].
AB  - OBJECTIVE: To establish a method for internal quality control (IQC) of sperm
      concentration test in the laboratory. METHODS: We set the concentrations of
      frozen semen at 20 x 10(6) and 80 x 10(6) as low and high concentrations of
      putative IQC products, with QC-BEADSTM quality control beads (QCBs) as the
      control. Using the double-blind method, four technicians determined the sperm
      concentrations of the IQC products and QCBs by computer-assisted sperm analysis,
      and drew a quality control chart (Xbar chart and Sbar chart) for each product.
      Through a month of continuous detection, we calculated and compared the intra-
      and inter-batch coefficients of variation (CV%) of the quality control products
      of high and low concentrations. RESULTS: The intra-batch coefficients of
      variation of the assumed IQC products of high and low concentrations were CV3.5%
      and CV2.4%, and their inter-batch coefficients of variation were CV10.2% and
      CV9.6%. The intra-batch coefficients of variation of the QCBs of high and low
      concentrations were CV5.1% and CV7.1%, and their inter-batch coefficients of
      variation were CV7.1% and CV8%. The intra-batch coefficients of variation of both
      IQC products and QCBs of high and low concentrations were <10%, and their inter
      batch coefficients of variation were <15%, which conformed to Levey-Jennings
      quality control principles and achieved IQC purposes. No significant differences
      were found in either intra- or inter-batch coefficients of variation between the
      IQC products and QCBs of high and low concentrations (P>0.05), indicating that
      assumed IQC products can replace QCBs for internal quality control in the
      laboratory. CONCLUSION: The IQC method we established for determining sperm
      concentration is simple, feasible and reliable.

PMID- 22474990
TI  - [Sperm DNA damage in young men working on the plateau].
AB  - OBJECTIVE: To investigate whether long working in the high-altitude area can
      damage sperm DNA in men. METHODS: We enlisted 51 service men stationed on the
      plateau in an observation group and another 53 living in the low-altitude area in
      a control group. We detected and compared the damages to sperm DNA in the semen
      samples from the two groups using single cell gel electrophoresis and the sperm
      chromatin dispersion test. RESULTS: The percentages of total, G1, G2 and G3 comet
      cells and abnormal sperm of the observation group were (5.56 +/- 3.98)%, (3.72 +/
      1.85)%, (1.57 +/- 1.07)%, (0.27 +/- 0.34)% and (16.59 +/- 12.07)%, respectively,
      before stationed on the plateau, but significantly increased at 6 months of
      plateau life ([11.15 +/- 8.59]%, [5.97 +/- 3.26]%, [3.83 +/- 2.13%, [1.35 +/-
      1.53]% and [22.03 +/- 15.33]%, P<0.05). The percentages of G2 comet cells and
      abnormal sperm were decreased to (3.32 +/- 1.83)% and (20.54 +/- 15.52)% at 12
      months, but still significantly higher than the baseline (P<0.05). CONCLUSION:
      Long working on the plateau may damage sperm DNA, but its influence on male
      fertility deserves further investigation. Therefore, it is important to reinforce
      reproductive health protection for males working on the plateau.

PMID- 22474991
TI  - [Relationship of sperm morphology with reproductive hormone levels in infertile
      men].
AB  - OBJECTIVE: To investigate the relationship of sperm morphology with reproductive
      hormones in infertile men and the pathogenesis of teratozoospermia. METHODS: This
      study included 90 infertile men aged 25 - 40 years. We measured their testis
      volumes using the Prader orchidometer, conducted routine semen analyses according
      to the WHO laboratory standard, and determined the concentrations of reproductive
      hormones and sex hormone-binding globulin (SHBG) by chemiluminescence and the
      levels of free testosterone (FT) and bioavailable testosterone (BioT). RESULTS:
      All the subjects showed normal sperm concentration. Based on the results of semen
      morphology analysis, the 90 infertile men were equally divided into groups 1
      (morphologically normal sperm <4%), 2 (morphologically normal sperm > or = 4% and
      <10%), and 3 (morphologically normal sperm > or = 10%), with no significant
      differences in age among the three groups (P>0.05). The volumes of the left
      testis were (14.27 +/- 3.65) ml, (16.90 +/- 3.57) ml and (14.57 +/- 3.57) ml,
      respectively (P = 0.006 group 1 vs group 2, P = 0.741 group 1 vs group 3, P =
      0.014 group 2 vs group 3), and those of the right testis were (14.60 +/- 3.70)
      ml, (16.60 +/- 3.35) ml and (14.67 +/- 3.54) ml, respectively (P = 0.050). There
      were no significant differences among the three groups in prolactin, follicle
      stimulating hormone, luteinising hormone, estradiol, total testosterone and SHBG,
      (P>0.05). The levels of serum FT were (0.25 +/- 0.07) nmol/L, (0.29 +/- 0.07)
      nmol/L and (0.31 +/- 0.13) nmol/L (P = 0.086 group 1 vs group 2, P= 0.010 group 1
      vs group 3, P= 0.364 group 2 vs group 3), and those of BioT were (5.81 +/- 1.58)
      nmol/L, (6.78 +/- 1.55) nmol/L and (7.29 +/- 3.02) nmol/L, respectively (P =
      0.086 group 1 vs group 2, P = 0.010 group 1 vs group 3, P = 0.364 group 2 vs
      group 3). The percentage of morphologically normal sperm was positively
      correlated with the levels of serum FT and BioT (P<0.05). CONCLUSION: The higher
      the levels of serum FT and BioT, the higher the percentage of morphologically
      normal sperm, which suggests that serum FT and BioT might be involved in the
      pathogenesis of teratozoospermia.

PMID- 22474992
TI  - [Influence of male age on the outcome of conventional IVF-ET].
AB  - OBJECTIVE: To study the influence of male age on the outcome of conventional IVF
      ET. METHODS: Based on male age, 170 couples undergoing conventional IVF-ET were
      divided into three groups: <35 yr (n = 60), 35 -39 yr (n = 77) and > or = 40 yr
      (n = 33). We observed the rates of fertilization, cleavage, good quality embryo,
      implantation, clinical pregnancy and abortion in different groups. RESULTS: There
      were no significant differences among the three groups in semen volume ([3.10 +/-
      1.22] ml vs [2.84 +/- 1.05] ml vs [2.80 +/- 0.79] ml), sperm concentration
      ([54.23 +/- 26.07] x 10(6)/ml vs [60.27 +/- 24.80] x 10(6)/ml vs [60.21 +/-
      27.42] x 10(6)/ml) and sperm viability ([53.93 +/- 13.25]% vs [56.10 +/- 16.58]%
      vs [51.82 +/- 15.45]%) (P>0.05). The men of the > or = 40 yr group showed a
      significantly lower percentage of grade a + b sperm ([40.97 +/- 11.91]%) than
      those of the <35 and 35 - 39 yr groups ([48.47 +/- 11.78]% and [46.84 +/-
      13.51]%) (P<0.05), and morphologically normal sperm ([11.76 +/- 5.97]%) than
      those of the <35 yr group ([15.25 +/- 6.94]% (P<0.05). The rates of
      fertilization, cleavage, good quality embryo, implantation, clinical pregnancy
      were 81.52%, 82.61%, 52.33%, 18.06% and 33.33% in the > or = 40 yr group, with no
      significant differences from those of the <35 yr group (83.18%, 82.68%, 56.99%,
      22.40% and 40.00%) and the 35 - 39 yr group (78.78%, 80.66%, 55.01%, 21.74% and
      38.96%) (P>0.05), while the abortion rate was markedly increased in the > or = 40
      yr group as compared with the <35 yr group (36.36% vs 8.33%, P>0.05). CONCLUSION:
      Increasing male age is related with decreasing percentages of progressively
      motile sperm and morphologically normal sperm, but not obviously with the rates
      of fertilization, good quality embryo, implantation, pregnancy and abortion.

PMID- 22474993
TI  - [Short-term medication of L-carnitine before intracytoplasmic sperm injection for
      infertile men with oligoasthenozoospermia].
AB  - OBJECTIVE: To observe the pregnancy promoting effect of L-carnitine combined with
      intracytoplasmic sperm injection (ICSI) in treating male infertility with
      oligoasthenozoospermia. METHODS: We assigned 129 patients with
      oligoasthenozoospermia to receive 2 weeks of oral L-carnitine followed by ICSI
      (medication group, n = 42) and ICSI alone (control group, n = 87). We compared
      the sperm concentration and motility, the percentage of grade a + b sperm, and
      sperm deformity before and after L-carnitine medication, as well as the rates of
      fertilization, cleavage, available embryo and clinical pregnancy between the two
      groups. RESULTS: The percentage of grade a + b sperm was significantly increased
      after L-carnitine medication as compared with the baseline ([13.5 +/- 10.7] % vs
      [9.6 +/- 7.2] %, P<0.05), and so was the rate of available embryo in the
      medication group after ICSI in comparison with that of the control group (77.50%
      vs 69.04%, P<0.05). CONCLUSION: Short-term medication of L-carnitine can improve
      sperm quality and raise the success rate of ICSI.

PMID- 22474994
TI  - [Clinical features of chronic epididymitis: report of 63 cases].
AB  - OBJECTIVE: To summarize the clinical features of chronic epididymitis (CE) for
      the purpose of improving its diagnosis and treatment. METHODS: According to the
      specific inclusion and exclusion criteria, we selected 63 CE patients in this
      study, obtained the data on their symptoms, signs, sexual activities, histories
      of related diseases, impact on quality of life and CE symptom indexes (CESI) by
      interrogation, physical examination and questionnaires, assessed their
      correlation with CE, and summarized the clinical features of the disease.
      RESULTS: The case group showed a similarity to the controls in age, ethnicity,
      education, smoking and drinking, but significantly larger numbers of sexual
      partners and patients with a history of urinary tract infections than the latter.
      Epididymal swelling and tenderness were found in 92.1%, and scrotal pain in 75.5%
      of the CE patients. CESI and the score of the impact on quality of life were 7.9
      +/- 4.6 and 12.5 +/- 5.6 in the case group, significantly higher than in the
      controls (4.4 +/- 3.2 and 8.5 +/- 4.2) (P<0.05). CONCLUSION: The significant
      signs of chronic epididymitis are epididymal swelling and tenderness, which
      affect the patient's quality of life. The association of chronic epididymitis
      with the number of sexual partners and history of urinary tract infections are
      yet to be further confirmed by larger-sample studies.

PMID- 22474995
TI  - [Chinese herbal drugs for erectile dysfunction through NO-cGMP-PDE5 signaling
      pathway].
AB  - Great progress has been made in the basic researches on erectile dysfunction (ED)
      ever since the recognition of the close association of micromolecular nitric
      oxide (NO) with penile smooth muscle relaxation in 1990. NO-cGMP-PDE5 signaling
      pathway plays an important role in regulating the relaxation of corpus cavernosum
      smooth muscle, and its relevant studies have contributed greatly to the clinical
      treatment of ED. Chinese herbal drugs have long been used in the treatment of ED,
      and the action mechanisms of some of them clarified through the NO-cGMP-PDE5
      signaling pathway. This article presents an overview on the recent advances in
      the studies of ED treatment with Chinese herbal drugs.

PMID- 22474996
TI  - [Application of tissue engineering technology and stem cells in urethral
      reconstruction].
AB  - Urethral defects caused by congenital abnormality, injury, inflammation or tumor
      are common diseases in urology. Conventional surgery of urethral reconstruction
      may lead to many complications, and its application has been greatly limited by
      insufficient supply of donor materials. Tissue engineering technology and stem
      cells can be used to construct biological substitutes for maintaining and
      repairing damaged tissue and organ function, which offers a new prospect for the
      strategies of urethral reconstruction.

PMID- 22474997
TI  - [Clinical efficacy of Yougui capsules and Wuziyanzong pills on
      oligoasthenospermia].
AB  - OBJECTIVE: To investigate the clinical effects of the Chinese traditional
      medicine Yougui Capsules and Wuziyanzong Pills on sperm viability and motility in
      patients with oligoasthenospermia. METHODS: A total of 80 infertile men
      oligoasthenospermia were equally randomized into a trial and a control group, the
      former treated with Yougui Capsules at 1.68 g tid, while the latter with
      Wuziyanzong Pills at 6 g bid, both for a course of 12 weeks. The sperm viability
      and motility of the patients were detected and compared before and after
      medication. RESULTS: After 12 weeks of medication, the sperm viability and
      percentages of grade a and grade a + b sperm were (65.7 +/- 13.1), (22.5 +/- 9.1)
      and (47.6 +/- 15.8)% in the trial group, significantly higher than (38.1 +/-
      11.1), (13.2 +/- 6.8) and (24.1 +/- 10.9)% in the control (P<0.05). What's more,
      the above three parameters of the two groups were also significantly higher than
      those before medication, which were (31.9 +/- 16.9), (8.2% +/- 3.7) and (15.7 +/-
      13.9)% in the former and (31.7 +/- 17.0), (7.9 +/- 4.5) and (16.9 +/- 13.6)% in
      the latter (P<0.05). CONCLUSION: Both Yougui Capsules and Wuziyanzong Pills can
      improve sperm viability and motility in patients with oligoasthenospermia, and
      the former is even more efficacious than the latter.

PMID- 22474998
TI  - [Sexual function inspection room for special penile insertion disorder].
AB  - OBJECTIVE: To determine the role of the sexual function inspection room in the
      treatment of patients with special penile insertion disorder. METHODS: This study
      included 6 couples received at the Andrology Clinic of Shanghai Renji Hospital
      from September, 2010 to February, 2011, who complained of being unable to
      accomplish sexual intercourse, all due to the husbands' abnormal penile erection.
      The couples had tried to make love 3 to 6 times after getting married, but never
      succeeded. Consequently the wives were planning to divorce, unwilling to attempt
      sexual activity again. We performed examinations and sexual education for the
      patients in the sexual function inspection room of Shanghai Institute of
      Andrology. The inspection room consisted of an inner and an outer section
      separated by a one-way transparent glass, through which what happened in the
      outer section could be observed from the inner section. The husband was given 20
      mg of tadalafil to induce penile erection, followed by Doppler ultrasonographic
      determination of penile hemodynamics. Meanwhile, the wife was allowed to observe
      her husband's penile erection through the glass to get sensory stimuli and
      relieve the mental burden. In the end, the doctor advised the couple to try
      sexual intercourse. RESULTS: In nature, the 6 wives were all impatient, while
      their husbands were all introverted. Doppler ultrasonography displayed normal
      penile hemodynamics. After sensory stimulation, the wives gained confidence in
      their husbands' erectile function. A one month follow-up visit showed that all
      the 6 couples could perform sexual intercourse normally. CONCLUSION: This sexual
      function inspection room can help doctors and wives to observe the status of the
      patient's penile erection, and meanwhile disburden the mind of the wives by
      giving them sensory stimuli, which contributes much to successful attempt at
      sexual intercourse.

PMID- 22474999
TI  - Paper-based analytical device for electrochemical flow-injection analysis of
      glucose in urine.
AB  - This article describes a new design for a paper-based electrochemical system for
      flow-injection analysis. Capillary wicking facilitates a gravity-driven flow of
      buffer solution continuously through paper and nitrocellulose, from a buffer
      reservoir at one end of the device to a sink at the other. A difference in height
      between the reservoir and the sink leads to a continuous and constant flow. The
      nitrocellulose lies horizontally on a working electrode, which consists of a thin
      platinum layer deposited on a solid support. The counter and reference electrodes
      are strategically positioned upstream in the buffer reservoir. A simple pipetting
      device was developed for reliable application of (sub)microliter volumes of
      sample without the need of commercial micropipets; this device did not damage the
      nitrocellulose membrane. Demonstration of the system for the determination of the
      concentration of glucose in urine resulted in a noninvasive, quantitative assay
      that could be used for diagnosis and monitoring of diabetes. This method does not
      require disposable test strips, with enzyme and electrodes, that are thrown away
      after each measurement. Because of its low cost, this system could be used in
      medical environments that are resource-limited.

PMID- 22475001
TI  - Response of crown ether functionalized polythiophenes to alkaline ions.
AB  - The sensing response of 15-crown-5-ether functionalized polythiophene to Li+,
      Na+, and K+ has been investigated at the atomistic level using molecular dynamics
      simulations. The stability associated with all the identified binding sites has
      been corroborated by quantum mechanical calculations. Although the cavity of the
      macrocycle is not the most visited binding site, such receptor is responsible of
      the selective sensing response of this polythiophene derivative. PF6(-)
      counterions reduce the mobility of the alkaline cations, which do not occupy the
      crown ether cavity of consecutive repeating units due to electrostatic
      repulsions. Furthermore, the relative entropy for the "free state -> bound state"
      has been estimated using a procedure based on the covariance matrix atom
      positional fluctuations. Evaluation of the entropic contributions allow us to
      complete the thermodynamics scenario of binding process, which was recently
      initiated by calculating the enthalpies at quantum mechanical level [ Chem. Eur.
      J. 2009, 15, 4676]. Results indicate an entropycally driven binding preference.

PMID- 22475000
TI  - Identifying new lignin bioengineering targets: impact of epicatechin, quercetin
      glycoside, and gallate derivatives on the lignification and fermentation of maize
      cell walls.
AB  - Apoplastic targeting of secondary metabolites compatible with monolignol
      polymerization may provide new avenues for designing lignins that are less
      inhibitory toward fiber fermentation. To identify suitable monolignol
      substitutes, primary maize cell walls were artificially lignified with normal
      monolignols plus various epicatechin, quercetin glycoside, and gallate
      derivatives added as 0 or 45% by weight of the precursor mixture. The flavonoids
      and gallates had variable effects on peroxidase activity, but all dropped
      lignification pH. Epigallocatechin gallate, epicatechin gallate, epicatechin
      vanillate, epigallocatechin, galloylhyperin, and pentagalloylglucose formed wall
      bound lignin at moderate to high concentrations, and their incorporation
      increased 48 h in vitro ruminal fiber fermentability by 20-33% relative to
      lignified controls. By contrast, ethyl gallate and corilagin severely depressed
      lignification and increased 48 h fermentability by about 50%. The results suggest
      several flavonoid and gallate derivatives are promising lignin bioengineering
      targets for improving the inherent fermentability of nonpretreated cell walls.

PMID- 22475002
TI  - Crystal structure and phototransistor behavior of N-substituted heptacence.
AB  - 6,8,15,17-Tetraaza-1.18,4.5,9.10,13.14-tetrabenzoheptacene (TTH, 1) has been
      prepared and characterized by single-crystal X-ray structure analysis. A
      phototransistor device based on TTH single crystal demonstrated that TTH showed a
      good performance in signal amplification under the photoconductive effect as well
      as photocontrolled switches.

PMID- 22475003
TI  - Wind power electricity: the bigger the turbine, the greener the electricity?
AB  - Wind energy is a fast-growing and promising renewable energy source. The
      investment costs of wind turbines have decreased over the years, making wind
      energy economically competitive to conventionally produced electricity. Size
      scaling in the form of a power law, experience curves and progress rates are used
      to estimate the cost development of ever-larger turbines. In life cycle
      assessment, scaling and progress rates are seldom applied to estimate the
      environmental impacts of wind energy. This study quantifies whether the trend
      toward larger turbines affects the environmental profile of the generated
      electricity. Previously published life cycle inventories were combined with an
      engineering-based scaling approach as well as European wind power statistics. The
      results showed that the larger the turbine is, the greener the electricity
      becomes. This effect was caused by pure size effects of the turbine (micro level)
      as well as learning and experience with the technology over time (macro level).
      The environmental progress rate was 86%, indicating that for every cumulative
      production doubling, the global warming potential per kWh was reduced by 14%. The
      parameters, hub height and rotor diameter were identified as Environmental Key
      Performance Indicators that can be used to estimate the environmental impacts for
      a generic turbine.

PMID- 22475005
TI  - Sex-specific mouse liver gene expression: genome-wide analysis of developmental
      changes from pre-pubertal period to young adulthood.
AB  - BACKGROUND: Early liver development and the transcriptional transitions during
      hepatogenesis are well characterized. However, gene expression changes during the
      late postnatal/pre-pubertal to young adulthood period are less well understood,
      especially with regards to sex-specific gene expression. METHODS: Microarray
      analysis of male and female mouse liver was carried out at 3, 4, and 8 wk of age
      to elucidate developmental changes in gene expression from the late postnatal/pre
      pubertal period to young adulthood. RESULTS: A large number of sex-biased and sex
      independent genes showed significant changes during this developmental period.
      Notably, sex-independent genes involved in cell cycle, chromosome condensation,
      and DNA replication were down regulated from 3 wk to 8 wk, while genes associated
      with metal ion binding, ion transport and kinase activity were up regulated. A
      majority of genes showing sex differential expression in adult liver did not
      display sex differences prior to puberty, at which time extensive changes in sex
      specific gene expression were seen, primarily in males. Thus, in male liver, 76%
      of male-specific genes were up regulated and 47% of female-specific genes were
      down regulated from 3 to 8 wk of age, whereas in female liver 67% of sex-specific
      genes showed no significant change in expression. In both sexes, genes up
      regulated from 3 to 8 wk were significantly enriched (p < E-76) in the set of
      genes positively regulated by the liver transcription factor HNF4alpha, as
      determined in a liver-specific HNF4alpha knockout mouse model, while genes down
      regulated during this developmental period showed significant enrichment (p < E
      65) for negative regulation by HNF4alpha. Significant enrichment of the
      developmentally regulated genes in the set of genes subject to positive and
      negative regulation by pituitary hormone was also observed. Five sex-specific
      transcriptional regulators showed sex-specific expression at 4 wk (male-specific
      Ihh; female-specific Cdx4, Cux2, Tox, and Trim24) and may contribute to the
      developmental changes that lead to global acquisition of liver sex-specificity by
      8 wk of age. CONCLUSIONS: Overall, the observed changes in gene expression during
      postnatal liver development reflect the deceleration of liver growth and the
      induction of specialized liver functions, with widespread changes in sex-specific
      gene expression primarily occurring in male liver.

PMID- 22475006
TI  - Cavitand-functionalized SWCNTs for N-methylammonium detection.
AB  - Single-walled carbon nanotubes (SWCNTs) have been functionalized with highly
      selective tetraphosphonate cavitand receptors. The binding of charged N
      methylammonium species to the functionalized SWCNTs was analyzed by X-ray
      photoelectron spectroscopy and confirmed by (31)P MAS NMR spectroscopy. The
      cavitand-functionalized SWCNTs were shown to function as chemiresistive sensory
      materials for the detection of sarcosine and its ethyl ester hydrochloride in
      water with high selectivity at concentrations as low as 0.02 mM. Exposure to
      sarcosine and its derivative resulted in an increased conductance, in contrast to
      a decreased conductance response observed for potential interferents such as the
      structurally related glycine ethyl ester hydrochloride.

PMID- 22475008
TI  - Dynamics of Coxiella burnetii antibodies and seroconversion in a dairy cow herd
      with endemic infection and excreting high numbers of the bacterium in the bulk
      tank milk.
AB  - Possible factors related to seropositivity and seroconversion to Coxiella
      burnetii were examined in a dairy herd with a high Coxiella-seroprevalence and
      high excretion levels of the bacterium in the bulk tank milk. Antibodies were
      detected by using a commercial ELISA test in 50.7% of 603 parous cows. The
      likelihood of C. burnetii seropositivity significantly increased by factors of
      1.87 and 1.61 for cows in their first and second terms of pregnancy,
      respectively, compared to non-pregnant cows. In 478 cows tested twice 12 months
      apart, the seroconversion rate was 5%. The likelihood of C. burnetii
      seroconversion was 2.27 times lower in multiparous than in primiparous cows and
      6.88 times higher in cows during their first 90 days in milk than dry-off cows.
      Our findings indicated a higher seroprevalence in the first and second terms of
      pregnancy, and that seroconversion mainly occurred in primiparous cows during
      their first 90 days in milk.

PMID- 22475007
TI  - A genome-wide study of two-component signal transduction systems in eight newly
      sequenced mutans streptococci strains.
AB  - BACKGROUND: Mutans streptococci are a group of gram-positive bacteria including
      the primary cariogenic dental pathogen Streptococcus mutans and closely related
      species. Two component systems (TCSs) composed of a signal sensing histidine
      kinase (HK) and a response regulator (RR) play key roles in pathogenicity, but
      have not been comparatively studied for these oral bacterial pathogens. RESULTS:
      HKs and RRs of 8 newly sequenced mutans streptococci strains, including S.
      sobrinus DSM20742, S. ratti DSM20564 and six S. mutans strains, were identified
      and compared to the TCSs of S. mutans UA159 and NN2025, two previously genome
      sequenced S. mutans strains. Ortholog analysis revealed 18 TCS clusters (HK-RR
      pairs), 2 orphan HKs and 2 orphan RRs, of which 8 TCS clusters were common to all
      10 strains, 6 were absent in one or more strains, and the other 4 were exclusive
      to individual strains. Further classification of the predicted HKs and RRs
      revealed interesting aspects of their putative functions. While TCS complements
      were comparable within the six S. mutans strains, S. sobrinus DSM20742 lacked
      TCSs possibly involved in acid tolerance and fructan catabolism, and S. ratti
      DSM20564 possessed 3 unique TCSs but lacked the quorum-sensing related TCS
      (ComDE). Selected computational predictions were verified by PCR experiments.
      CONCLUSIONS: Differences in the TCS repertoires of mutans streptococci strains,
      especially those of S. sobrinus and S. ratti in comparison to S. mutans, imply
      differences in their response mechanisms for survival in the dynamic oral
      environment. This genomic level study of TCSs should help in understanding the
      pathogenicity of these mutans streptococci strains.

PMID- 22475009
TI  - Influence of the subsurface composition of a material on the adhesion of 
      staphylococci.
AB  - Controlling the interface between bacteria and solid materials has become an
      important task in biomedical science. For a fundamental and comprehensive
      understanding of adhesion it is necessary to seek quantitative information about
      the involved interactions. Most studies concentrate on the modification of the
      surface (chemical composition, hydrophobicity, or topography) neglecting,
      however, the influence of the bulk material, which always contributes to the
      overall interaction via van der Waals forces. In this study, we applied AFM force
      spectroscopy and flow chamber experiments to probe the adhesion of 
      Staphylococcus carnosus  to a set of tailored Si wafers, allowing for a
      separation of short- and long-range forces. We provide experimental evidence that
      the subsurface composition of a substrate influences bacterial adhesion. A coarse
      estimation of the strength of the van der Waals forces via the involved Hamaker
      constants substantiates the experimental results. The results demonstrate that
      the uppermost layer is not solely responsible for the strength of adhesion.
      Rather, for all kinds of adhesion studies, it is equally important to consider
      the contribution of the subsurface.

PMID- 22475011
TI  - Utilization of the ferrous sulfate (Fricke) dosimeter for evaluating the
      radioprotective potential of cystamine: experiment and Monte Carlo simulation.
AB  - Cystamine, an organic disulfide (RSSR), is among the best of the known radiation
      protective compounds and has been used to protect normal tissues in clinical
      radiation therapy. Recently, it has also proved to be beneficial in the treatment
      of disorders of the central nervous system in animal models. However, the
      underlying mechanism of its action at the chemical level is not yet well
      understood. The present study aims at using the ferrous sulfate (Fricke)
      dosimeter to quantitatively evaluate, both experimentally and theoretically, the
      radioprotective potential of this compound. The well-known radiolysis of the
      Fricke dosimeter by (60)Co gamma rays or fast electrons, based on the oxidation
      of ferrous ions to ferric ions by the oxidizing species (*)OH, HO(2)(*), and
      H(2)O(2) produced in the radiolytic decomposition of water, forms the basis for
      our method. The presence of cystamine in Fricke dosimeter solutions during
      irradiation prevents the radiolytic oxidation of Fe(2+) and leads to decreased
      ferric yields (or G values). The observed decrease in G(Fe(3+)) increases upon
      increasing the concentration of the disulfide compound over the range 0-0.1 M
      under both aerated and deaerated conditions. To help assess the basic radiation
      protective mechanism of this compound, a full Monte Carlo computer code is
      developed to simulate in complete detail the radiation-induced chemistry of the
      studied Fricke/cystamine solutions. Benefiting from the fact that cystamine is
      reasonably well characterized in terms of radiation chemistry, this computer
      model proposes reaction mechanisms and incorporates specific reactions describing
      the radiolysis of cystamine in aerated and deaerated Fricke solutions that lead
      to the observable quantitative chemical yields. Results clearly indicate that the
      protective effect of cystamine originates from its radical-capturing ability,
      which allows this compound to act by competing with the ferrous ions for the
      various free radicals--especially (*)OH radicals and H(*) atoms--formed during
      irradiation of the surrounding water. Most interestingly, our simulation modeling
      also shows that the predominant pathway in the oxidation of cystamine by (*)OH
      radicals involves an electron-transfer mechanism, yielding RSSR(*+) and OH(-). A
      very good agreement is found between calculated G(Fe(3+)) values and experiment.
      This study concludes that Monte Carlo simulations represent a very efficient
      method for understanding indirect radiation damage at the molecular level.

PMID- 22475010
TI  - An in vitro perspective to cholinesterase inhibitory and antioxidant activity of
      five Gentiana species and Gentianella caucasea.
AB  - The dichloromethane (DCM), ethyl acetate (EtOAc), and methanol extracts from the
      leaves, roots, and flowers of the five species of Gentiana (Gentiana asclepiadea,
      Gentiana cruciata, Gentiana olivieri, Gentiana septemfida, and Gentiana verna)
      and Gentianella caucasea were investigated for their inhibitory activity against
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant
      effect using 2,2-diphenyl-1-picrylhydrazyl radical scavenging, metal-chelation
      capacity, and ferric-reducing antioxidant power assays. Total phenol and
      flavonoid contents of the extracts were determined spectrophotometrically. The
      presence of some characteristic compounds found in Gentiana species
      (gentiopicroside, swertiamarin, isoorientin, isovitexin and vitexin) was analyzed
      in the extracts by thin layer chromatography. The flower DCM extract of G. verna
      exerted the highest inhibition against AChE (53.65 +/- 1.03%), whereas the root
      EtOAc extract of G. cruciata was the most effective in BChE inhibition assay
      (50.72 +/- 0.75%) at 100 MUg ml-1. The extracts of G. verna were also found to be
      more active in the antioxidant tests.

PMID- 22475012
TI  - Effect of low-energy electron irradiation on DNA damage by Fe3+ ion.
AB  - We investigated the combined effects of low-energy electron irradiation and
      Fe(3+) ion on DNA damage. We used lyophilized pBR322 plasmid DNA films with
      various concentrations (0 ~ 7 mM) of Fe(3+) ions and irradiation with
      monochromatic, low-energy 3 or 5 eV electrons for these studies. DNA-Fe(3+) films
      were recovered and analyzed by agarose gel electrophoresis to identify and
      compare the effects of Fe(3+) ions and/or low-energy electrons alone or in
      combination on DNA damage. In nonirradiated DNA-Fe(3+) films, there was little
      DNA damage observed (less than 10% of the total DNA loaded on the gel appeared
      damaged) for Fe(3+) ion up to 7 mM concentration. In irradiated DNA films without
      Fe(3+) ions, there was also very little DNA damage observed (less than 3% of the
      total DNA loaded on the gel appeared damaged). However, when DNA-Fe(3+) films,
      were irradiated with low-energy electrons, DNA damage was significantly increased
      compared to the sum of the damage caused both by either Fe(3+) ion or low-energy
      electrons irradiation alone. We proposed that both DEA and/or electron transfer
      processes might play a role in the enhanced DNA damage when DNA-Fe(3+) films were
      irradiated by low-energy electrons.

PMID- 22475013
TI  - Occurrence and role of umami molecules in foods.
AB  - Glutamate is a multifunctional amino acid. It plays a key role in central
      neurotransmission, in intermediate metabolism of carbohydrate as well as in
      taste, representing the major ligand having the umami taste. Glutamate is one of
      the main constituents of dietary proteins and is also consumed in many prepared
      foods as a flavour enhancer in the form of glutamate salts. Umami perception is
      based on multiple receptor systems distributed in the oral cavity and in the
      gastrointestinal tract which activates a number of regions of the brain involved
      in different functions, from food identification to the formation of an affective
      value related to a particular food, which may influence appetitive behaviour.
      Future research on umami taste and umami compounds will be fundamental in gaining
      a better understanding of their physiological significance and to promote their
      status in a healthy and pleasant diet.

PMID- 22475014
TI  - Glaucogenin E, a new C21 steroid from Cynanchum stauntonii.
AB  - Glaucogenin E (1), a new C(21) steroid sapogenin, along with three known ones (2
      4) were isolated from the rhizomes of Cynanchum stauntonii (Decne.) Schltr. ex
      Levl. Their structures were established mainly by the spectroscopic analysis,
      including 2D NMR. All the isolated compounds were evaluated for their
      cytotoxicity against human cancer cell lines HeLa, Bel-7402, SGC-7901 and BGC
      823.

PMID- 22475015
TI  - A hypothesis on biological protection from space radiation through the use of new
      therapeutic gases as medical counter measures.
AB  - Radiation exposure to astronauts could be a significant obstacle for long
      duration manned space exploration because of current uncertainties regarding the
      extent of biological effects. Furthermore, concepts for protective shielding also
      pose a technically challenging issue due to the nature of cosmic radiation and
      current mass and power constraints with modern exploration technology. The
      concern regarding exposure to cosmic radiation is biological damage that is
      associated with increased oxidative stress. It is therefore important and would
      be enabling to mitigate and/or prevent oxidative stress prior to the development
      of clinical symptoms and disease. This paper hypothesizes a "systems biology"
      approach in which a combination of chemical and biological mitigation techniques
      are used conjunctively. It proposes using new, therapeutic, medical gases as
      chemical radioprotectors for radical scavenging and as biological signaling
      molecules for management of the body's response to exposure. From reviewing
      radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and
      mechanisms of radiation biology, it can be concluded that this approach may have
      therapeutic potential for radiation exposure. Furthermore, it also appears to
      have similar potential for curtailing the pathogenesis of other diseases in which
      oxidative stress has been implicated including cardiovascular disease, cancer,
      chronic inflammatory disease, hypertension, ischemia/reperfusion (IR) injury,
      acute respiratory distress syndrome, Parkinson's and Alzheimer's disease,
      cataracts, and aging. We envision applying these therapies through inhalation of
      gas mixtures or ingestion of water with dissolved gases.

PMID- 22475016
TI  - A highly sensitive, dual-readout assay based on gold nanoparticles for
      organophosphorus and carbamate pesticides.
AB  - This report presents a highly sensitive, rhodamine B-covered gold nanoparticle
      (RB-AuNP) -based assay with dual readouts (colorimetric and fluorometric) for
      detecting organophosphorus and carbamate pesticides in complex solutions. The
      detection mechanism is based on the fact that these pesticides can inhibit the
      activity of acetylcholinesterase (AChE), thus preventing the generation of
      thiocholine (which turns the RB-AuNP solutions blue and unquenches the
      fluorescence of RB simultaneously). The color of the RB-AuNP solution remains red
      and the fluorescence of RB remains quenched. By use of this dual-readout assay,
      the lowest detectable concentrations for several kinds of pesticides including
      carbaryl, diazinon, malathion, and phorate were measured to be 0.1, 0.1, 0.3, and
      1 MUg/L, respectively, all of which are much lower than the maximum residue
      limits (MRL) as reported in the European Union pesticides database as well as
      those from the U.S. Department Agriculture (USDA). This assay allows detection of
      pesticides in real samples such as agricultural products and river water. The
      results in detecting pesticide residues collected from food samples via this
      method agree well with those from high-performance liquid chromatography (HPLC).
      This simple assay is therefore suitable for sensing pesticides in complex
      samples, especially in combination with other portable platforms.

PMID- 22475017
TI  - Highly efficient, inverted polymer solar cells with indium tin oxide modified
      with solution-processed zwitterions as the transparent cathode.
AB  - Polymer solar cells (PSCs) with inverted structure can greatly improve
      photovoltaic stability. This paper reports a novel method to lower the work
      function of indium tin oxide (ITO) through the modification with a thin layer of
      zwitterions which have both positive and negative charges in the same molecule.
      Zwitterions have a strong dipole moment due to the presence of the two types of
      charges and are immobile under electric field. Zwitterions with both conjugated
      and saturated structure were investigated. A zwitterion thin layer is formed on
      ITO by spin coating a methanol solution of the zwitterion. The zwitterion
      modified ITO sheets can be used as the cathode for the electron collection of
      inverted PSCs. The inverted poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid
      methyl ester (P3HT:PC(61)BM) PSCs can exhibit photovoltaic efficiency as high as
      3.98% under simulated AM1.5G illumination (100 mW cm(-2)), which is comparable to
      that of PSCs with normal architecture. The effective electron collection by the
      zwitterion-modified ITO sheets is attributed to the reduction of the work
      function of ITO as a result of the dipole moment by the zwitterions. The
      zwitterion modification can lower the work function of ITO by up to 0.97 eV. The
      photovoltaic performance of PSCs and the reduction in the work function of ITO
      strongly depend on the chemical structure of the zwitterions.

PMID- 22475018
TI  - Whole genome comparisons of Fragaria, Prunus and Malus reveal different modes of
      evolution between Rosaceous subfamilies.
AB  - BACKGROUND: Rosaceae include numerous economically important and morphologically
      diverse species. Comparative mapping between the member species in Rosaceae have
      indicated some level of synteny. Recently the whole genome of three crop species,
      peach, apple and strawberry, which belong to different genera of the Rosaceae
      family, have been sequenced, allowing in-depth comparison of these genomes.
      RESULTS: Our analysis using the whole genome sequences of peach, apple and
      strawberry identified 1399 orthologous regions between the three genomes, with a
      mean length of around 100 kb. Each peach chromosome showed major orthology mostly
      to one strawberry chromosome, but to more than two apple chromosomes, suggesting
      that the apple genome went through more chromosomal fissions in addition to the
      whole genome duplication after the divergence of the three genera. However, the
      distribution of contiguous ancestral regions, identified using the multiple
      genome rearrangements and ancestors (MGRA) algorithm, suggested that the Fragaria
      genome went through a greater number of small scale rearrangements compared to
      the other genomes since they diverged from a common ancestor. Using the
      contiguous ancestral regions, we reconstructed a hypothetical ancestral genome
      for the Rosaceae 7 composed of nine chromosomes and propose the evolutionary
      steps from the ancestral genome to the extant Fragaria, Prunus and Malus genomes.
      CONCLUSION: Our analysis shows that different modes of evolution may have played
      major roles in different subfamilies of Rosaceae. The hypothetical ancestral
      genome of Rosaceae and the evolutionary steps that lead to three different
      lineages of Rosaceae will facilitate our understanding of plant genome evolution
      as well as have a practical impact on knowledge transfer among member species of
      Rosaceae.

PMID- 22475019
TI  - L- and D-proline adsorption by chiral ordered mesoporous silica.
AB  - Chiral ordered mesoporous silica (COMS) was synthesized in the presence of amino
      acid proline by combining tetraethyl orthosilicate and quaternized aminosilane
      silica sources. The as-prepared materials were activated by calcination or
      microwave chemical extraction to remove the organic templates. The powder X-ray
      diffraction and N2 adsorption characterization revealed in COMS the structural
      and textural features of MCM-41-type silica. The chirality of the material was
      disclosed by mixed and separate L- and D-proline adsorption on the COMS prepared
      with L-proline (L-Pro-COMS) and D-proline (d-Pro-COMS). It was found that the
      maximum L-proline and D-proline adsorption capacities on L-Pro-COMS were ca. 2.3
      and 0.6 mmol/g, respectively, while the adsorption of D-proline was higher than
      that of l-proline on d-Pro-COMS. Finally, both activation routes yielded
      enantioselective silicas able to separate proline racemate.

PMID- 22475020
TI  - Development of highly ordered nanofillers in zein nanocomposites for improved
      tensile and barrier properties.
AB  - It has been a long-lasting challenge to prepare highly ordered biopolymer
      nanocomposites to optimize or tune the desired mechanical and barrier properties
      of the nanocomposite film. In this study, we developed a simple and cost
      effective method to synthesize highly ordered zein nanocomposites. The method
      involved the synthesis of magnetic iron oxide (Fe(3)O(4)) nanofiller and the
      preparation of a highly ordered structure by in situ nanofiller reorientation
      under an external magnetic field. The successful preparation of Fe(3)O(4)
      magnetic nanoplatelets together with exfoliated and highly ordered zein resin
      nanocomposites was confirmed by scanning electron microscopy, X-ray diffraction,
      and a vibrating sample magnetometer. As a result, in comparison to zein resin
      film, the exfoliated zein nanocomposites (Fe-Zein) showed dramatic improvement on
      mechanical and barrier properties. The tensile strength, elongation, and Young's
      modulus of Fe-Zein were increased by 218, 48, and 264%, respectively, while the
      water vapor and oxygen permeability decreased by 68 and 29%. More importantly,
      the highly ordered zein nanocomposites (Fe-Zein-Mag) showed additional
      improvement on the mechanical and gas barrier properties. In comparison to Fe
      Zein, the tensile strength and elongation of Fe-Zein-Mag were increased by 10 and
      48%, respectively, and a 30% decrease in Young's Modulus was observed, indicating
      the Fe-Zein-Mag film was more elastic. Besides, the water vapor and oxygen
      permeability of Fe-Zein-Mag were also decreased by an additional 48 and 17%,
      respectively.

PMID- 22475021
TI  - Electrochemical reduction of carbon dioxide in an MFC-MEC system with a layer-by
      layer self-assembly carbon nanotube/cobalt phthalocyanine modified electrode.
AB  - Electrochemical reduction of carbon dioxide (CO(2)) to useful chemical materials
      is of great significance to the virtuous cycle of CO(2). However, some problems
      such as high overpotential, high applied voltage, and high energy consumption
      exist in the course of the conventional electrochemical reduction process. This
      study presents a new CO(2) reduction technique for targeted production of formic
      acid in a microbial electrolysis cell (MEC) driven by a microbial fuel cell
      (MFC). The multiwalled carbon nanotubes (MWCNT) and cobalt tetra-amino
      phthalocyanine (CoTAPc) composite modified electrode was fabricated by the layer
      by-layer (LBL) self-assembly technique. The new electrodes significantly
      decreased the overpotential of CO(2) reduction, and as cathode successfully
      reduced CO(2) to formic acid (production rate of up to 21.0 +/- 0.2 mg.L(-1).h(
      1)) in an MEC driven by a single MFC. Compared with the electrode modified by
      CoTAPc alone, the MWCNT/CoTAPc composite modified electrode could increase the
      current and formic acid production rate by approximately 20% and 100%,
      respectively. The Faraday efficiency for formic acid production depended on the
      cathode potential. The MWCNT/CoTAPc composite electrode reached the maximum
      Faraday efficiency at the cathode potential of ca. -0.5 V vs Ag/AgCl. Increasing
      the number of electrode modification layers favored the current and formic acid
      production rate. The production of formic acid was stable in the MFC-MEC system
      after multiple batches of CO(2) electrolysis, and no significant change was
      observed on the performances of the modified electrode. The coupling of the
      catalytic electrode and the bioelectrochemical system realized the targeted
      reduction of CO(2) in the absence of external energy input, providing a new way
      for CO(2) capture and conversion.

PMID- 22475022
TI  - The mechanisms of RNA SHAPE chemistry.
AB  - The biological functions of RNA are ultimately governed by the local environment
      at each nucleotide. Selective 2'-hydroxyl acylation analyzed by primer extension
      (SHAPE) chemistry is a powerful approach for measuring nucleotide structure and
      dynamics in diverse biological environments. SHAPE reagents acylate the 2'
      hydroxyl group at flexible nucleotides because unconstrained nucleotides
      preferentially sample rare conformations that enhance the nucleophilicity of the
      2'-hydroxyl. The critical corollary is that some constrained nucleotides must be
      poised for efficient reaction at the 2'-hydroxyl group. To identify such
      nucleotides, we performed SHAPE on intact crystals of the Escherichia coli
      ribosome, monitored the reactivity of 1490 nucleotides in 16S rRNA, and examined
      those nucleotides that were hyper-reactive toward SHAPE and had well-defined
      crystallographic conformations. Analysis of these conformations revealed that 2'
      hydroxyl reactivity is broadly facilitated by general base catalysis involving
      multiple RNA functional groups and by two specific orientations of the bridging
      3'-phosphate group. Nucleotide analog studies confirmed the contributions of
      these mechanisms to SHAPE reactivity. These results provide a strong mechanistic
      explanation for the relationship between SHAPE reactivity and local RNA dynamics
      and will facilitate interpretation of SHAPE information in the many technologies
      that make use of this chemistry.

PMID- 22475023
TI  - Molecular role of catalase on oxidative stress-induced Ca(2+) signaling and TRP
      cation channel activation in nervous system.
AB  - BACKGROUND: Catalase catalyzes the reduction of H(2)O(2) to water and it can also
      remove organic hydroperoxides. Nervous system in body is especially sensitive to
      free radical damage due to rich content of easily oxidizible fatty acids and
      relatively low content of antioxidants including catalase. Recent studies
      indicate that reactive oxygen species actually target active channel function, in
      particular TRP channels. I review the effects of catalase on Ca(2+) signaling and
      on TRP channel activation in neuroglial cells such as microglia and substantia
      nigra. MATERIALS: Review of the relevant literature and results from recent our
      basic studies, as well as critical analyses of published systematic reviews were
      obtained from the pubmed and the Science Citation Index. RESULTS: It was observed
      that oxidative stress-induced activations of TRPM2, TRPC3, TRPC5 and TRPV1 cation
      channels in neuronal cells are modulated by catalase, suggesting antioxidant
      dependent activation/inhibition of the channels. I provide also, a general
      overview of the most important oxidative stress-associated changes in neuronal
      mitochondrial Ca(2+) homeostasis due to oxidative stress-induced channel
      neuropathies. Catalase incubation induces protective effects on rat brain
      mitochondrial function and neuronal survival. A decrease in catalase activity
      through oxidative stress may have an important role in etiology of Parkinson's
      disease and sensory pain. CONCLUSION: The TRP channels can be activated by
      oxidative stress products, opening of nonspecific cation channels would result in
      Ca(2+) influx, and then elevation of cytoplasmic free Ca(2+) could stimulate
      mitochondrial Ca(2+) uptake. Catalase modulates oxidative stress-induced Ca(2+)
      influx and some TRP channels activity in neuronal cells.

PMID- 22475024
TI  - Frequency of consumption of foods and beverages by Inuvialuit adults in Northwest
      Territories, Arctic Canada.
AB  - Limited data exist regarding nutrient intakes and overall dietary quality in
      Canadian Arctic populations. This cross-sectional study determined the frequency
      of consumption of traditional meats (e.g. caribou, polar bear, seal, char and
      whale) and non-traditional store-bought foods including non-traditional meats
      (e.g. beef, pork and chicken), grains, dairy, fruits, vegetables and non-nutrient
      dense foods (NNDFs) (e.g. butter, chocolate, chips, candy and pop) by Inuvialuit
      adults (175 women, mean age 44 +/- 14 years; 55 men, mean age 41 +/- 13 years) in
      three remote communities in the Northwest Territories. Using a validated
      quantitative food frequency questionnaire, frequency of consumption over a 30-day
      period was determined for 141 commonly reported foods. Mean consumption of
      traditional meats (1.6 times/day), fruits (1 time/day) and vegetables (0.6
      times/day) was less frequent than that of NNDFs (5.0 times/day). Nutritional
      intervention strategies are needed to promote more frequent consumption of
      nutrient-rich foods and less frequent consumption of NNDFs in these Arctic
      communities.

PMID- 22475025
TI  - Chemical composition and synergistic interaction between aminoglycosides
      antibiotics and essential oil of Lantana montevidensis Briq.
AB  - The chemical composition of the essential oil from Lantana montevidensis Briq.
      and its antibiotic resistance modifying activity were investigated by gas
      chromatography/mass spectrometry (GC/MS) and microdilution assay, respectively.
      beta-Caryophyllene (31.50%), germacrene D (27.50%) and bicyclogermacrene (13.93%)
      were the main constituents. The essential oil was examined for antibiotic
      activity alone in association with aminoglycosides against Escherichia coli Ec27
      and Staphylococcus aureus Sa358. The results showed antibacterial activities of
      the oil and synergistic effects combined with aminoglycosides. The most
      expressive effect was the potentiating of amikacin on E. coli with minimal
      inhibitory concentration decrease (512-5 ug mL(-1)). The data obtained are
      indicative of the antibacterial activity of the essential oil of L. montevidensis
      and its potential in modifying the resistance of aminoglycosides analysed.

PMID- 22475026
TI  - Plant polyphenols as electron donors for erythrocyte plasma membrane redox
      system: validation through in silico approach.
AB  - BACKGROUND: The plasma membrane redox system (PMRS) has extensively been studied
      in erythrocytes. The PMRS plays an important role in maintaining plasma redox
      balance and provides a protective mechanism against oxidative stress. Earlier it
      was proposed that only NADH or NADPH provided reducing equivalents to PMRS;
      however, now it is acknowledged that some polyphenols also have the ability to
      donate reducing equivalents to PMRS. METHODS: Two different docking simulation
      softwares, Molegro Virtual Docker and Glide were used to study the interaction of
      certain plant polyphenols viz. quercetin, epigallocatechin gallate, catechin
      epicatechin and resveratrol with human erythroyte NADH-cytochrome b5 reductase,
      which is a component of PMRS and together with the identification of minimum
      pharmacophoric feature using Pharmagist. RESULTS: The derived common minimum
      pharmacophoric features show the presence of minimum bioactive component in all
      the selected polyphenols. Our results confirm wet lab findings which show that
      these polyphenols have the ability to interact and donate protons to the Human
      NADH-cytochrome b5 reductase. CONCLUSION: With the help of these comparative
      results of docking simulation and pharmacophoric features, novel potent molecules
      can be designed with higher efficacy for activation of the PMRS system.

PMID- 22475027
TI  - Antioxidant activity of trans-resveratrol toward hydroxyl and hydroperoxyl
      radicals: a quantum chemical and computational kinetics study.
AB  - In this work, we have carried out a systematic study of the antioxidant activity
      of trans-resveratrol toward hydroxyl ((*)OH) and hydroperoxyl ((*)OOH) radicals
      in aqueous simulated media using density functional quantum chemistry and
      computational kinetics methods. All possible mechanisms have been considered:
      hydrogen atom transfer (HAT), proton-coupled electron transfer (PCET), sequential
      electron proton transfer (SEPT), and radical adduct formation (RAF). Rate
      constants have been calculated using conventional transition state theory in
      conjunction with the Collins-Kimball theory. Branching ratios for the different
      paths contributing to the overall reaction, at 298 K, are reported. For the
      global reactivity of trans-resveratrol toward (*)OH radicals, in water at
      physiological pH, the main mechanism of reaction is proposed to be the sequential
      electron proton transfer (SEPT). However, we show that trans-resveratrol always
      reacts with (*)OH radicals at a rate that is diffusion-controlled, independent of
      the reaction pathway. This explains why trans-resveratrol is an excellent but
      very unselective (*)OH radical scavenger that provides antioxidant protection to
      the cell. Reaction between trans-resveratrol and the hydroperoxyl radical occurs
      only by phenolic hydrogen abstraction. The total rate coefficient is predicted to
      be 1.42 * 10(5) M(-1) s(-1), which is much smaller than the ones for reactions of
      trans-resveratrol with (*)OH radicals, but still important. Since the (*)OOH half
      life time is several orders larger than the one of the (*)OH radical, it should
      contribute significantly to trans-resveratrol oxidation in aqueous biological
      media. Thus, trans-resveratrol may act as an efficient (*)OOH, and also
      presumably (*)OOR, radical scavenger.

PMID- 22475028
TI  - Size-controlled flow synthesis of gold nanoparticles using a segmented flow
      microfluidic platform.
AB  - Segmented flow is often used in the synthesis of nanomaterials to achieve narrow
      particle size distribution. The narrowness of the distribution is commonly
      attributed to the reduced dispersion associated with segmented flows. On the
      basis of the analysis of flow fields and the resulting particle size
      distribution, we demonstrate that it is the slip velocity between the two fluids
      and internal mixing in the continuous-phase slugs that govern the nature of the
      particle size distribution. The reduction in the axial dispersion has less impact
      on particle growth and hence on the particle size distribution. Synthesis of gold
      nanoparticles from HAuCl(4) with rapid reduction by NaBH(4) serves as a model
      system. Rapid reduction yields gold nuclei, which grow by agglomeration, and it
      is controlled by the interaction of the nuclei with local flow. Thus, the
      difference in the physical properties of the two phases and the inlet flow rates
      ultimately control the particle growth. Hence, a careful choice of continuous and
      dispersed phases is necessary to control the nanoparticle size and size
      distribution.

PMID- 22475029
TI  - Identification and diversity of multiresistant Corynebacterium striatum clinical
      isolates by MALDI-TOF mass spectrometry and by a multigene sequencing approach.
AB  - BACKGROUND: The genus Corynebacterium is composed of gram-positive bacteria that
      are widely distributed throughout the environment; these bacteria are also part
      of the normal microbiota of human skin and mucous membranes. Multiple studies
      have shown that species of this genus, including C. striatum, become pathogenic
      to humans under special conditions. Our aim was to determine the characteristics
      of clinical multiresistant strains of C. striatum that were isolated in our
      geographical region, to determine their diversity, and to compare them with the
      type strain and with related species. We studied fifty-two strains of C. striatum
      isolated from different hospitals from Mallorca, Spain, mainly from the Hospital
      Joan March in Bunyola, Mallorca. Most of the strains were isolated from sputum
      cultures of respiratory samples from patients with chronic obstructive pulmonary
      disease. To gain further insight into the genetic diversity of the strains, we
      analysed several housekeeping genes and other genes associated with antibiotic
      resistance. Strains were also characterised phenotypically by their antibiotic
      resistance profiles and by MALDI-TOF mass spectrometry analysis. RESULTS: The
      ITS1 region, gyrA and rpoB were chosen as the appropriate genes in the C.
      striatum genome to study the genetic diversity of C. striatum species and to
      discriminate between strains. After analysing these three genes, four sequence
      types (ST2, ST4, ST1 and ST11) were found to be the most abundant. Splits tree
      analysis of the strains demonstrated that these clinical isolates did not share
      any alleles with the type strain of the species. Recombination was detected
      within all of the C. striatum isolates, and different clonal populations were
      detected within the samples. CONCLUSIONS: Our results demonstrate that the
      isolates were best identified using gene-based molecular methods; using these
      methods, the isolated strains were determined to be different from the type
      strain of C. striatum. The ITS1 region and the gyrA and rpoB genes were selected
      because of their variability and were the most useful tools for discriminating
      between strains. The phenotype and antibiotype characteristics of the strains did
      not seem suitable for typing purposes. MALDI-TOF mass spectrometry can be a
      useful method for identifying and discriminating between C. striatum strains.

PMID- 22475030
TI  - Amine-rich polyelectrolyte multilayers for patterned surface fixation of
      nanostructures.
AB  - We describe a lithographic method for directly patterning the adhesive properties
      of amine-rich layer-by-layer assembled polymer films, useful for positioning
      metal and other nanostructures. The adhesive properties of the films are
      sufficiently robust that the films can be patterned with standard as opposed to
      soft lithographic methods. We perform the patterning with a lithographically
      defined evaporated aluminum mask which protects selected regions of the
      substrate, passivating adhesion in the exposed regions with acetic anhydride.
      When the aluminum is removed with a HCl etch, the protected regions retain their
      adhesion, whereas particle adsorption is almost completely eliminated in the
      passivated areas, making it possible to guide adsorption to the protected areas.
      The high degree of adhesion comes about because of uncoordinated amine groups
      that pervade the film. Cycling the pH from high values to low and back causes the
      amines to be rearranged, rejuvenating the adhesive properties of the surface,
      which is the likely origin of the robustness of the adhesive properties to
      processing. pH adjustment also causes reversible swelling and deswelling of the
      film, so that the vertical position and dielectric environment of the
      nanostructure can be dynamically adjusted, which can be particularly beneficial
      for tuning the plasmonic resonances of metallic structures.

PMID- 22475031
TI  - Quantification of phosphatidic acid in foodstuffs using a thin-layer
      chromatography-imaging technique.
AB  - Apical application of lysophosphatidic acid (LPA), a growth-factor-like
      phospholipid, was shown to prevent or restore gastrointestinal (GI) disorders,
      such as diarrhea and stomach ulcer, in experimental animals. Because LPA is
      formed from phosphatidic acid (PA) by the activity of digestive phospholipase
      A(2), PA is a potential component for dietary treatment of such GI disorders.
      Here, we quantified PA contained in 38 foodstuffs and 3 herbs by a thin-layer
      chromatography-imaging technique. Vegetables belonging to Brassicaceae, such as
      cabbage leaves (700 nmol/g of wet weight) and Japanese radish leaves (570
      nmol/g), contained higher amounts of PA than other foodstuffs. Amounts of PA in
      fruits, cereals, and starchy root vegetables were below 300 nmol/g. Animal
      foodstuffs contained low amounts of PA (<60 nmol/g). Interestingly, leaves of
      Mallotus japonicas, a Japanese edible herb used for treatment of stomach ulcer,
      had the highest PA (1410 nmol/g) among those examined. The data shown here will
      be useful for the development of dietary treatment for a damaged GI tract.

PMID- 22475032
TI  - Dirhodium paddlewheel with functionalized carboxylate bridges: new building block
      for self-assembly and immobilization on solid support.
AB  - A new dirhodium(II,II) paddlewheel complex, [Rh(2)(O(2)CC(6)H(4)COOC(2)H(5))(4)]
      (1), has been synthesized using a predesigned functionalized carboxylate, namely,
      4-(ethoxycarbonyl)benzoate. The target product has been crystallized from the
      acetone solution and structurally characterized as a bis-acetone adduct,
      [Rh(2)(O(2)CC(6)H(4)COOC(2)H(5))(4)(OCMe(2))(2)].C(6)H(14) (2). By utilizing the
      ability of dangling ester groups to coordinate to open axial ends of neighboring
      dirhodium units, 1 can self-assemble to form 2D networks upon crystallization
      from solutions of noncoordinating solvents such as chlorobenzene and chloroform.
      The resulting [Rh(2)(O(2)CC(6)H(4)COOC(2)H(5))(4)].2C(6)H(5)Cl (3) and
      [Rh(2)(O(2)CC(6)H(4)COOC(2)H(5))(4)].2CHCl(3) (4) products have microporous solid
      state structures with the pores filled with the corresponding disordered solvent
      molecules. Notably, 3 and 4 represent unique examples of 2D extended frameworks
      based on dirhodium tetracarboxylate paddlewheel units devoid of any exogenous
      ligands. In solution, the dangling ends of carboxylate bridges of 1 have been
      successfully utilized for condensation reaction with the selected solid support,
      benzylamine-functionalized polystyrene, allowing successful heterogenization of
      dirhodium units through the equatorial covalent attachment to the substrate. The
      resulting solid product was tested as a catalyst in the cyclopropanation reaction
      of styrene with methyl phenyldiazoacetate to show good yields and
      diastereoselectivity.

PMID- 22475033
TI  - Modulation of action potential and calcium signaling by levetiracetam in rat
      sensory neurons.
AB  - Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy,
      has been used in pain treatment but the cellular mechanism of this action remains
      unclear. This study aimed to investigate effects of LEV on the excitability and
      membrane depolarization-induced calcium signaling in isolated rat sensory neurons
      using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging
      techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and
      cultured following enzymatic and mechanical dissociation. Under current clamp
      conditions, acute application of LEV (30 uM, 100 uM and 300 uM) significantly
      increased input resistance and caused the membrane to hyperpolarize from resting
      membrane potential in a dose-dependent manner. Reversal potentials of action
      potential (AP) after hyperpolarising amplitudes were shifted to more negative,
      toward to potassium equilibrium potentials, after application of LEV. It also
      caused a decrease in number of APs in neurons fired multiple APs in response to
      prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed
      that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited
      to 97.8 +/- 4.6% (n = 17), 92.6 +/- 4.8% (n = 17, p < 0.01) and 89.1 +/- 5.1% (n
      = 18, p < 0.01) after application of 30 uM, 100 uM and 300 uM LEV (respectively),
      without any significant effect on basal levels of [Ca(2+)](i). This is the first
      evidence for the effect of LEV on the excitability of rat sensory neurons through
      an effect which might involve activation of potassium channels and inhibition of
      entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain
      treatment modalities.

PMID- 22475034
TI  - Conformations and reactions of bicyclo[3.2.1]oct-6-en-8-ylidene.
AB  - Bicyclo[3.2.1]oct-6-en-8-ylidene (1) can assume either the conformation of
      "classical" carbene 1a or that of foiled carbene 1b in which the divalent carbon
      bends toward the double bond. Oxadiazoline precursors for the generation of 1
      were prepared, followed by photochemical and thermal decomposition as well as
      flash vacuum pyrolysis (FVP) of a tosyl hydrazone sodium salt precursor, to give
      a number of rearrangement products. Matrix isolation experiments demonstrate the
      presence of a diazo intermediate and methyl acetate in all photochemical and
      thermal precursor reactions. The major product from rearrangements of "classical"
      bridged carbene 1a is bicyclo[3.3.0]octa-1,3-diene as a result of an alkyl shift,
      while dihydrosemibullvalene formed from a 1,3-C-H insertion. In contrast, thus
      far unknown strained bicyclo[4.2.0]octa-1,7-diene formed by a vinyl shift in
      foiled carbene 1b. The experimental results are corroborated by density
      functional theory (DFT), MP2, and G4 computations.

PMID- 22475035
TI  - Fitness of Escherichia coli strains carrying expressed and partially silent IncN
      and IncP1 plasmids.
AB  - BACKGROUND: Understanding the survival of resistance plasmids in the absence of
      selective pressure for the antibiotic resistance genes they carry is important
      for assessing the value of interventions to combat resistant bacteria. Here,
      several poorly explored questions regarding the fitness impact of IncP1 and IncN
      broad host range plasmids on their bacterial hosts are examined; namely, whether
      related plasmids have similar fitness impacts, whether this varies according to
      host genetic background, and what effect antimicrobial resistance gene silencing
      has on fitness. RESULTS: For the IncP1 group pairwise in vitro growth competition
      demonstrated that the fitness cost of plasmid RP1 depends on the host strain. For
      the IncN group, plasmids R46 and N3 whose sequence is presented for the first
      time conferred remarkably different fitness costs despite sharing closely related
      backbone structures, implicating the accessory genes in fitness. Silencing of
      antimicrobial resistance genes was found to be beneficial for host fitness with
      RP1 but not for IncN plasmid pVE46. CONCLUSIONS: These findings suggest that the
      fitness impact of a given plasmid on its host cannot be inferred from results
      obtained with other host-plasmid combinations, even if these are closely related.

PMID- 22475036
TI  - A new abietane diterpenoid from Salvia xanthocheila Boiss.
AB  - From the chloroform extract of aerial part of Salvia xanthocheila Boiss. one new
      abietane diterpenoid, xantoquinone (5alpha,6alpha-dimethoxy-7,11,14-trioxoabieta
      8,12-diene) and one known oleanene triterpenoid namely 1beta,3beta-dihydroxy-12
      oleanene were isolated. The structure of the new terpenoid was elucidated by
      comprehensive spectroscopic analysis including electron ionisation-mass spectra,
      (1)H NMR, (13)C NMR, distortionless enchancement by polarisation transfer, H,H
      correlation spectroscopy, heteronuclear multiple-quantum coherence and
      heteronuclear multiple-bond correlation.

PMID- 22475037
TI  - Antimicrobial studies of unsymmetrical bis-1,2,3-triazoles.
AB  - Aryl azides were treated with allenylmagnesium bromide to generate 1,5
      disubstituted butynyl 1,2,3-triazoles in a domino fashion, which upon Cu(I)
      catalyzed 1,3-dipolar cycloaddition with aryl azides afforded novel bis-1,2,3
      triazoles in quantitative yields. The final products were analyzed for their
      antimicrobial activities against a panel of bacterial and fungal strains which
      revealed the products to be potent antimicrobials.

PMID- 22475038
TI  - Influence of surface-attachment functionality on the aggregation, persistence,
      and electron-transfer reactivity of chalcogenorhodamine dyes on TiO2.
AB  - Chalcogenorhodamine dyes bearing phosphonic acids and carboxylic acids were
      compared as sensitizers of nanocrystalline TiO(2) in dye-sensitized solar cells
      (DSSCs). The dyes were constructed around a 3,6
      bis(dimethylamino)chalcogenoxanthylium core and varied in the 9 substituent: 5
      carboxythien-2-yl in dyes 1-E (E = O, Se), 4-carboxyphenyl in dyes 2-E (E = O,
      S), 5-phosphonothien-2-yl in dyes 3-E (E = O, Se), and 4-phosphonophenyl in dyes
      4-E (E = O, Se). All dyes adsorbed to TiO(2) as mixtures of H aggregates and
      monomers, which exhibited broadened absorption spectra relative to those of
      purely amorphous monolayers. Surface coverages of dyes and the extent of H
      aggregation varied minimally with the surface-attachment functionality, the
      structure of the 9-aryl group, and the identity of the chalcogen heteroatom.
      Carboxylic acid-functionalized dyes 1-E and 2-E desorbed rapidly and completely
      from TiO(2) into acidified CH(3)CN, but phosphonic acid-functionalized dyes 3-E
      and 4-E persisted on TiO(2) for days. Short-circuit photocurrent action spectra
      of DSSCs corresponded closely to the absorptance spectra of dye-functionalized
      films; thus, H aggregation did not decrease the electron-injection yield or
      charge-collection efficiency. Maximum monochromatic incident photon-to-current
      efficiencies (IPCEs) of DSSCs ranged from 53 to 95% and were slightly higher for
      carboxylic acid-functionalized dyes 1-E and 2-E. Power-conversion efficiencies of
      DSSCs under white-light illumination were low (<1%), suggesting that dye
      regeneration was inefficient at high light intensities. The photoelectrochemical
      performance (under monochromatic or white-light illumination) of 1-E and 2-E
      decayed significantly within 20-80 min of the assembly of DSSCs, primarily
      because of the desorption of the dyes. In contrast, the performance of phosphonic
      acid-functionalized dyes remained stable or improved slightly on similar
      timescales. Thus, replacing carboxylic acids with phosphonic acids increased the
      inertness of chalcogenorhodamine-TiO(2) interfaces without greatly impacting the
      aggregation of dyes or the interfacial electron-transfer reactivity.

PMID- 22475039
TI  - The artificial leaf.
AB  - To convert the energy of sunlight into chemical energy, the leaf splits water via
      the photosynthetic process to produce molecular oxygen and hydrogen, which is in
      a form of separated protons and electrons. The primary steps of natural
      photosynthesis involve the absorption of sunlight and its conversion into
      spatially separated electron-hole pairs. The holes of this wireless current are
      captured by the oxygen evolving complex (OEC) of photosystem II (PSII) to oxidize
      water to oxygen. The electrons and protons produced as a byproduct of the OEC
      reaction are captured by ferrodoxin of photosystem I. With the aid of ferrodoxin
      NADP(+) reductase, they are used to produce hydrogen in the form of NADPH. For a
      synthetic material to realize the solar energy conversion function of the leaf,
      the light-absorbing material must capture a solar photon to generate a wireless
      current that is harnessed by catalysts, which drive the four electron/hole fuel
      forming water-splitting reaction under benign conditions and under 1 sun (100
      mW/cm(2)) illumination.  This Account describes the construction of an artificial
      leaf comprising earth-abundant elements by interfacing a triple junction,
      amorphous silicon photovoltaic with hydrogen- and oxygen-evolving catalysts made
      from a ternary alloy (NiMoZn) and a cobalt-phosphate cluster (Co-OEC),
      respectively. The latter captures the structural and functional attributes of the
      PSII-OEC. Similar to the PSII-OEC, the Co-OEC self-assembles upon oxidation of an
      earth-abundant metal ion from 2+ to 3+, may operate in natural water at room
      temperature, and is self-healing. The Co-OEC also activates H(2)O by a proton
      coupled electron transfer mechanism in which the Co-OEC is increased by four hole
      equivalents akin to the S-state pumping of the Kok cycle of PSII. X-ray
      absorption spectroscopy studies have established that the Co-OEC is a structural
      relative of Mn(3)CaO(4)-Mn cubane of the PSII-OEC, where Co replaces Mn and the
      cubane is extended in a corner-sharing, head-to-tail dimer.  The ability to
      perform the oxygen-evolving reaction in water at neutral or near-neutral
      conditions has several consequences for the construction of the artificial leaf.
      The NiMoZn alloy may be used in place of Pt to generate hydrogen. To stabilize
      silicon in water, its surface is coated with a conducting metal oxide onto which
      the Co-OEC may be deposited. The net result is that immersing a triple-junction
      Si wafer coated with NiMoZn and Co-OEC in water and holding it up to sunlight can
      effect direct solar energy conversion via water splitting. By constructing a
      simple, stand-alone device composed of earth-abundant materials, the artificial
      leaf provides a means for an inexpensive and highly distributed solar-to-fuels
      system that employs low-cost systems engineering and manufacturing. Through this
      type of system, solar energy can become a viable energy supply to those in the
      non-legacy world.

PMID- 22475040
TI  - Halogen oxidation and halogen photoelimination chemistry of a platinum-rhodium
      heterobimetallic core.
AB  - The heterobimetallic complexes, PtRh(tfepma)(2)(CN(t)Bu)X(3) (X = Cl, Br), are
      assembled by the treatment of Pt(cod)X(2) (cod =1,5-cyclooctadiene) with
      {Rh(cod)X}(2), in the presence of tert-butylisonitrile (CN(t)Bu) and tfepma
      (tfepma = bis(trifluoroethoxyl)phosphinomethylamine). The neutral complexes
      contain Pt-Rh single bonds with metal-metal separations of 2.6360(3) and
      2.6503(7) A between the square planar Pt and octahedral Rh centers for the Cl and
      Br complexes, respectively. Oxidation of the XPt(I)Rh(II)X(2) cores with suitable
      halide sources (PhICl(2) or Br(2)) furnishes PtRh(tfepma)(2)(CN(t)Bu)X(5), which
      preserves a Pt-Rh bond. For the chloride system, the initial oxidation product
      orients the platinum-bound chlorides in a meridional geometry, which slowly
      transforms to a facial arrangement in pentane solution as verified by X-ray
      crystal analysis. Irradiation of the mer- or fac-Cl(3)Pt(III)Rh(II)Cl(2) isomers
      with visible light in the presence of olefin promotes the photoelimination of
      halogen and regeneration of the reduced ClPt(I)Rh(II)Cl(2) core. In addition to
      exhibiting photochemistry similar to that of the chloride system, the oxidized
      bromide cores undergo thermal reduction chemistry in the presence of olefin with
      zeroth-order olefin dependence. Owing to an extremely high photoreaction quantum
      yield for the fac-ClPt(I)Rh(II)Cl(2) isomer, details of the X(2) photoelimination
      have been captured by transient absorption spectroscopy. We now report the first
      direct observation of the photointermediate that precedes halogen reductive
      elimination. The intermediate is generated promptly upon excitation (<8 ns), and
      halogen is eliminated from it with a rate constant of 3.6 * 10(4) s(-1). As M-X
      photoactivation and elimination is the critical step in HX splitting, these
      results establish a new guidepost for the design of HX splitting cycles for solar
      energy storage.

PMID- 22475041
TI  - The potential mechanism for the different expressions of gelatinases induced by
      all-trans retinoic acid in different cells.
AB  - Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix
      metalloproteinase-9 (MMP-9). The increased expressions of gelatinases are
      implicated in the pathogenesis of cell injury and cell death. All-trans retinoic
      acid (ATRA) is an import biological agent which can regulate the expressions of
      gelatinases and take part in cell injury and cell death. ATRA exerts its
      biological effect by the high-affinity binding to retinoic acid receptors (RARs).
      The RARs consist of three isoforms: RAR-alpha, RAR-beta and RAR-gamma. However,
      it is interesting that the effect of ATRA on the expressions of gelatinases is
      different in different cells. There is no report to explore the possible
      mechanism for it at present. In this context, we review the published reports and
      draw a hypothesis that: (i) The distributions of RARs isoforms are different in
      different cells; (ii) ATRA activates the different RARs isoforms in different
      cells; (iii) The roles of different RARs isoforms for regulating the expression
      of MMP-2 or MMP-9 are different in different cells. So, ATRA takes a different
      function on the expressions of MMP-2 and MMP-9 in different cells. Once the
      potential strategy can be successfully confirmed, it would be prone to comprehend
      why the ATRA regulates the different expressions of gelatinases in different
      cells.

PMID- 22475042
TI  - Treatment patterns and economic burden of metastatic and recurrent locally
      advanced head and neck cancer patients.
AB  - OBJECTIVE: To characterize treatment patterns and measure the economic burden
      associated with metastatic (mHNC) and recurrent, locally-advanced head and neck
      cancer (rHNC). METHODS: Administrative claims from Medicare- and privately
      insured individuals during 2004-2008 were used in this retrospective database
      study of patients with advanced HNC. Patients diagnosed with HNC were matched 1:1
      to cancer-free controls to measure the incremental economic burden of HNC.
      Outcomes of interest were measured during the 6 months following the date of a
      secondary tumor diagnosis for metastatic patients or the date of a diagnosis
      indicating rHNC. To assess treatment patterns, HNC patients were evaluated for
      the use frequency of treatments (radiotherapy, chemotherapy and surgery). Costs
      were reported in 2008 US$ from a third-party payer perspective and were analyzed
      using generalized linear models and two-part regression models adjusting for
      differences in age and baseline Charlson Comorbidity Index (excluding cancer
      diagnoses) between the HNC and control cohorts. Components of cost included
      inpatient, outpatient and other medical services as well as pharmacy costs.
      RESULTS: The mHNC cohort consisted of 1042 patients and the rHNC cohort included
      324 patients. The most common treatments for mHNC patients were supportive care
      (90.2%), radiation therapy (48.5%), surgery (41.9%) and chemotherapy (38.3%).
      Patients with rHNC frequently received HNC-related supportive care (71.0%),
      radiation therapy (67.9%) and chemotherapy (27.2%); HNC-related surgery was
      infrequent (12.7%) during the study period. The 6-month incremental adjusted
      total costs were $60,414 per patient for mHNC and $21,141 per patient for rHNC
      (p<0.0001). Approximately 46-58% of the incremental cost was attributable to
      outpatient visits, 27-37% to inpatient costs and 11-13% to pharmacy, depending on
      the HNC cohort. LIMITATIONS: The identification of mHNC/rHNC was based on
      diagnosis codes and treatment patterns with the limitation of the claims
      database. CONCLUSIONS: Metastatic and recurrent, locally-advanced HNC patients
      frequently receive cancer-related treatments and incur substantial economic
      burden.

PMID- 22475043
TI  - Impact of spacer and strand length on oligonucleotide conjugation to the surface
      of ligand-free laser-generated gold nanoparticles.
AB  - Gold nanoparticles conjugated to nucleic acids are widely used for biomedical
      targeting and sensing applications; however, little is known about the
      conjugation chemistry covering the impact of steric dimension and strand
      orientation of single-stranded oligonucleotides (ssO) on the conjugation process
      and binding efficiencies. In this context, we present an extensive investigation
      concerning the attachment of thiolated ssO to the surface of laser-generated gold
      nanoparticles, altering both strand length and binding orientation by the
      insertion of different spacer types at either the 3' or 5' ssO terminus. A
      significant reduction of conjugation efficiency of about 30-50% is determined for
      spacer-prolonged bionanoconjugates due to coiling effects of the flexible ssO
      strand on the particle surface which increases deflection angle of
      oligonucleotides and limits the number of biomolecules attached to the
      nanoparticles. 

PMID- 22475044
TI  - Hantavirus pulmonary syndrome: prognostic factors for death in reported cases in
      Brazil.
AB  - Hantavirus pulmonary syndrome (HPS) was described for the first time in Brazil in
      1993 and has occurred endemically throughout the country. This study analysed
      clinical and laboratory aspects as well as death-related factors for HPS cases in
      Brazil from 1993 to 2006. The investigation comprised a descriptive and
      exploratory study of the history of cases as well as an analytical retrospective
      cohort survey to identify prognostic factors for death due to HPS. A total of 855
      Brazilian HPS cases were assessed. The majority of cases occurred during spring
      (33.5%) and winter (27.6%), mainly among young male adults working in rural
      areas. The global case fatality rate was 39.3%. The mean interval between the
      onset of symptoms and hospitalisation was 4 days and that between hospitalisation
      and death was 1 day. In the multiple regression analysis, adult respiratory
      distress syndrome and mechanical respiratory support were associated with risk of
      death; when these two variables were excluded from the model, dyspnoea and
      haemoconcentration were associated with a higher risk of death.

PMID- 22475045
TI  - Comment on "Probing the thermodynamics of competitive ion binding using minimum
      energy structures".

PMID- 22475046
TI  - Effects of cyclin D1 gene amplification and protein expression on time to
      recurrence in postmenopausal breast cancer patients treated with anastrozole or
      tamoxifen: a TransATAC study.
AB  - INTRODUCTION: Gene amplification of CCND1 is observed in a subgroup of breast
      cancers with poor prognosis, whereas overexpression of the protein cyclin D1 has
      been linked to both worse and better clinical outcome. CCND1 amplification and
      protein overexpression have also been associated with resistance to treatment
      with tamoxifen or even to a potentially detrimental effect of tamoxifen. METHODS:
      To clarify these challenging and partly contrasting treatment predictive and
      prognostic links for cyclin D1 we analysed a large cohort of postmenopausal
      breast cancer patients randomised to receive either adjuvant anastrozole or
      tamoxifen, as part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC)
      trial. The CCND1 amplification status and protein expression of cyclin D1 were
      assessed by chromogenic in situ hybridisation and immunohistochemistry,
      respectively, in 1,155 postmenopausal, oestrogen-receptor-positive breast cancer
      patients included in the TransATAC substudy. RESULTS: Amplification of CCND1 was
      observed in 8.7% of the tumours and was associated with increased risk of disease
      recurrence (hazard ratio = 1.61; 95% confidence interval, 1.08 to 2.41) after
      adjustment for other clinicopathological parameters. In contrast, nuclear
      expression of cyclin D1 protein was associated with decreased recurrence rate
      (hazard ratio = 0.6; 95% confidence interval, 0.39 to 0.92). The intensity of
      nuclear or cytoplasmic expression was not of prognostic value. There was no
      significant interaction between cyclin D1 status and treatment efficacy, ruling
      out any major detrimental effect of tamoxifen in CCND1-amplified postmenopausal
      breast cancer. CONCLUSIONS: In summary, CCND1 amplification and low nuclear
      expression of cyclin D1 predicted poor clinical outcome in postmenopausal breast
      cancer patients treated with either anastrozole or tamoxifen. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN18233230.

PMID- 22475047
TI  - A new amide and a new monoterpene from the seeds of Clausena lansium.
AB  - A new amide (2) and a new monoterpene (6) were isolated from the seeds of
      Clausena lansium together with four known ones (1, 3-5). The structures of the
      new compounds were elucidated by extensive spectroscopic analyses. The absolute
      configurations of 1, 2 and 6 were determined by optical rotation and the modified
      Mosher's method.

PMID- 22475048
TI  - Selective excitation 1D-NMR experiments for the assignment of the absolute
      configuration of secondary alcohols.
AB  - Routine selective excitation experiments, easy to set up on modern NMR
      spectrometers, allow for the determination of the absolute configuration of
      chiral secondary alcohols by double derivatization directly in the NMR tube. As a
      general method, TOCSY1D with selective excitation of the alpha proton in the MPA
      esters and with a short mixing time reveals only the nearby protons in the
      coupling network. Typically, the analysis takes less than 30 min. A longer mixing
      time, selective excitation of other signals, or NOESY1D experiments can be used
      for measuring DeltadeltaRS of other protons.

PMID- 22475049
TI  - Potency, selectivity and prolonged binding of saxagliptin to DPP4: maintenance of
      DPP4 inhibition by saxagliptin in vitro and ex vivo when compared to a rapidly
      dissociating DPP4 inhibitor.
AB  - BACKGROUND: Dipeptidylpeptidase 4 (DPP4) inhibitors have clinical benefit in
      patients with type 2 diabetes mellitus by increasing levels of glucose-lowering
      incretin hormones, such as glucagon-like peptide -1 (GLP-1), a peptide with a
      short half life that is secreted for approximately 1 hour following a meal. Since
      drugs with prolonged binding to their target have been shown to maximize
      pharmacodynamic effects while minimizing drug levels, we developed a time
      dependent inhibitor that has a half-life for dissociation from DPP4 close to the
      duration of the first phase of GLP-1 release. RESULTS: Saxagliptin and its active
      metabolite (5-hydroxysaxagliptin) are potent inhibitors of human DPP4 with
      prolonged dissociation from its active site (Ki = 1.3 nM and 2.6 nM, t1/2 = 50
      and 23 minutes respectively at 37 degrees C). In comparison, both vildagliptin
      (3.5 minutes) and sitagliptin ( < 2 minutes) rapidly dissociated from DPP4 at 37
      degrees C. Saxagliptin and 5-hydroxysaxagliptin are selective for inhibition of
      DPP4 versus other DPP family members and a large panel of other proteases, and
      have similar potency and efficacy across multiple species.Inhibition of plasma
      DPP activity is used as a biomarker in animal models and clinical trials.
      However, most DPP4 inhibitors are competitive with substrate and rapidly
      dissociate from DPP4; therefore, the type of substrate, volume of addition and
      final concentration of substrate in these assays can change measured inhibition.
      We show that unlike a rapidly dissociating DPP4 inhibitor, inhibition of plasma
      DPP activity by saxagliptin and 5-hydroxysaxagliptin in an ex vivo assay was not
      dependent on substrate concentration when substrate was added rapidly because
      saxagliptin and 5-hydroxysaxagliptin dissociate slowly from DPP4, once bound. We
      also show that substrate concentration was important for rapidly dissociating
      DPP4 inhibitors. CONCLUSIONS: Saxagliptin and its active metabolite are potent,
      selective inhibitors of DPP4, with prolonged dissociation from its active site.
      They also demonstrate prolonged inhibition of plasma DPP4 ex vivo in animal
      models, which implies that saxagliptin and 5-hydroxysaxagliptin would continue to
      inhibit DPP4 during rapid increases in substrates in vivo.

PMID- 22475050
TI  - Effect of small for gestational age on hemodynamic parameters in the neonatal
      period.
AB  - OBJECTIVE: The time course over which hypertension develops in children with a
      history of growth restriction has not been fully elucidated. The purpose of this
      study was to determine whether commonly obtained hemodynamic parameters were
      different between small for gestational age (SGA) and appropriate for gestational
      age (AGA) neonates. METHODS: This was a retrospective case-control study matching
      24 SGA neonates in a 1:2 fashion with 48 AGA neonates delivered during the same
      gestational week. Hemodynamic parameters were evaluated during the first week of
      life and the week prior to discharge. RESULTS: There were no differences in blood
      pressure (BP) parameters during the first week of life. Compared to AGA controls,
      SGA neonates had a significantly lower heart rate (HR) at birth (148.2 +/- 19.2
      vs. 159.2 +/- 17.1, p < 0.001), and a greater need for vasopressor support (OR
      5.66; 95% CI 2.28, 14.04). The SGA neonates had a lower systolic BP during the
      week prior to discharge (68.3 +/- 1.2 vs. 73.5 +/- 1.2 mmHg, p < 0.001).
      CONCLUSIONS: SGA newborns had a lower HR at birth and greater need for
      vasopressor support during the first week of life despite similar BP parameters.
      SGA newborns had a lower systolic BP prior to discharge. Further studies are
      needed to understand the progression to adult hypertension.

PMID- 22475051
TI  - Radical coupling reactions in lignin synthesis: a density functional theory
      study.
AB  - Lignin is a complex, heterogeneous polymer in plant cell walls that provides
      mechanical strength to the plant stem and confers resistance to degrading
      microbes, enzymes, and chemicals. Lignin synthesis initiates through oxidative
      radical-radical coupling of monolignols, the most common of which are p-coumaryl,
      coniferyl, and sinapyl alcohols. Here, we use density functional theory to
      characterize radical-radical coupling reactions involved in monolignol
      dimerization. We compute reaction enthalpies for the initial self- and cross
      coupling reactions of these monolignol radicals to form dimeric intermediates via
      six major linkages observed in natural lignin. The 8-O-4, 8-8, and 8-5 coupling
      are computed to be the most favorable, whereas the 5-O-4, 5-5, and 8-1 linkages
      are less favorable. Overall, p-coumaryl self- and cross-coupling reactions are
      calculated to be the most favorable. For cross-coupling reactions, in which each
      radical can couple via either of the two sites involved in dimer formation, the
      more reactive of the two radicals is found to undergo coupling at its site with
      the highest spin density. 

PMID- 22475052
TI  - Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122)
      in relapsed chronic lymphocytic leukemia.
AB  - Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of
      CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity
      (ADCC). We evaluated lucatumumab in a phase I clinical trial in chronic
      lymphocytic leukemia (CLL). Twenty-six patients with relapsed CLL were enrolled
      on five different dose cohorts administered weekly for 4 weeks. The maximally
      tolerated dose (MTD) of lucatumumab was 3.0 mg/kg. Four patients at doses of 4.5
      mg/kg and 6.0 mg/kg experienced grade 3 or 4 asymptomatic elevated amylase and
      lipase levels. Of the 26 patients enrolled, 17 patients had stable disease (mean
      duration of 76 days, range 29-504 days) and one patient had a nodular partial
      response for 230 days. Saturation of CD40 receptor on CLL cells was uniform at
      all doses post-treatment but also persisted at trough time points in the 3.0
      mg/kg or greater cohorts. At the MTD, the median half-life of lucatumumab was 50
      h following the first infusion, and 124 h following the fourth infusion. In
      summary, lucatumumab had acceptable tolerability, pharmacokinetics that supported
      chronic dosing and pharmacodynamic target antagonism at doses of 3.0 mg/kg, but
      demonstrated minimal single-agent activity. Future efforts with lucatumumab in
      CLL should focus on combination-based therapy.

PMID- 22475053
TI  - Testing local-scale panmixia provides insights into the cryptic ecology,
      evolution, and epidemiology of metazoan animal parasites.
AB  - When every individual has an equal chance of mating with other individuals, the
      population is classified as panmictic. Amongst metazoan parasites of animals,
      local-scale panmixia can be disrupted due to not only non-random mating, but also
      non-random transmission among individual hosts of a single host population or non
      random transmission among sympatric host species. Population genetics theory and
      analyses can be used to test the null hypothesis of panmixia and thus, allow one
      to draw inferences about parasite population dynamics that are difficult to
      observe directly. We provide an outline that addresses 3 tiered questions when
      testing parasite panmixia on local scales: is there greater than 1 parasite
      population/species, is there genetic subdivision amongst infrapopulations within
      a host population, and is there asexual reproduction or a non-random mating
      system? In this review, we highlight the evolutionary significance of non
      panmixia on local scales and the genetic patterns that have been used to identify
      the different factors that may cause or explain deviations from panmixia on a
      local scale. We also discuss how tests of local-scale panmixia can provide a
      means to infer parasite population dynamics and epidemiology of medically
      relevant parasites.

PMID- 22475054
TI  - Changes in gait pattern and hip muscle strength after open reduction and internal
      fixation of acetabular fracture.
AB  - OBJECTIVES: To characterize changes in the gait pattern at 3 and 12 months after
      surgery for acetabular fracture, to assess the relationship between various gait
      parameters and hip muscle strength, and to determine the factors associated with
      gait disorders that correlate with gait parameters measured at 12 months after
      surgery. DESIGN: Prospective cohort study. SETTING: University hospital.
      PARTICIPANTS: Patients (N=19) with acetabular fractures were treated by open
      reduction and internal fixation (ORIF) and examined at 3 and 12 months
      postoperatively. The study also included a similar number of sex- and age-matched
      control subjects. INTERVENTIONS: Postoperative rehabilitation program. MAIN
      OUTCOME MEASURES: Spatiotemporal, kinematic, and kinetic variables of gait and
      strength of hip flexor, adductor, and abductor muscles at 3 and 12 months after
      ORIF. RESULTS: Walking velocity at 3 months after ORIF was slower in the patients
      than in the control subjects; however, walking velocity at 12 months was similar
      in the 2 groups. Although most of the kinematic and kinetic variables showed
      recovery to control levels at 3 and 12 months after ORIF, recovery was incomplete
      for pelvic forward tilt and hip abduction moment even at 12 months after ORIF.
      The greatest loss of muscle strength was noted in the hip abductors, where the
      average deficit was 35.4% at 3 months and 24.6% at 12 months. There was a
      significant relationship between hip abductor muscle strength and hip abduction
      moment at 3 months (R(2)=.63); however, this relationship diminished at 12 months
      (R(2)=.14). The presence of associated injuries correlated with lack of recovery
      of the peak hip abduction moment. CONCLUSIONS: Pelvic forward tilt and peak hip
      abduction moment showed incomplete recovery at 12 months after ORIF with
      subsequent conventional and home exercise rehabilitation programs. Our results
      suggest that improvement of hip abductor muscle strength in the early
      postoperative period could improve the peak hip abduction moment.

PMID- 22475055
TI  - Reliability and validity of step test scores in subjects with chronic stroke.
AB  - OBJECTIVES: To establish (1) the intrarater and interrater reliabilities of step
      test (ST) scores in subjects with chronic stroke, (2) the ST's known-groups
      validity and cutoff scores for distinguishing subjects with chronic stroke from
      healthy adults older than 50 years, and (3) the convergent validity of ST scores
      with lower-limb muscle strength, coordination, balance performance, and walking
      speed. DESIGN: Cross-sectional study. SETTING: University-based rehabilitation
      center. PARTICIPANTS: Convenience sample of subjects (N=30): community-dwelling
      subjects with chronic stroke (n=15) and healthy adults older than 50 years
      (n=15). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: ST scores; handheld
      dynamometer measurements of bilateral lower-limb muscle strength; lower-extremity
      motor coordination test (LEMOCOT) scores; Berg Balance Scale scores; walking
      speed as measured by a 5-meter walk test. RESULTS: ST scores showed excellent
      intrarater reliability, with intraclass correlation coefficients ranging from
      .981 to .995 and interrater reliability ranging from .996 to .999. A cutoff score
      of 13 on the paretic side was found to distinguish the healthy adults older than
      50 years from subjects with stroke at a sensitivity of 87% and a specificity of
      87%. A cutoff score of 11 on the nonparetic side was found to distinguish the
      healthy adults from subjects with stroke at a sensitivity of 100% and a
      specificity of 67%. ST scores of the paretic limb demonstrated a significant
      correlation with muscle strength, the LEMOCOT scores of the paretic leg, and
      walking speed. ST scores of the nonparetic limb demonstrated a significant
      correlation with muscle strength and the LEMOCOT scores of the paretic leg.
      CONCLUSIONS: The ST is a reliable measurement tool when the number of steps is
      counted by either experienced or inexperienced examiners by viewing videotapes.
      ST scores with both the paretic limb and the nonparetic limb are sensitive in
      distinguishing subjects with chronic stroke from healthy adults older than 50
      years.

PMID- 22475056
TI  - Age differences in expectations and readiness regarding lifestyle modifications
      in individuals at high risk of diabetes.
AB  - OBJECTIVE: The main objective of this study was to determine whether expectations
      and readiness to modify eating habits and physical activity (PA) level are
      different between young and older individuals with prediabetes who agreed to
      participate in a lifestyle modification program. DESIGN: Cross-sectional
      analysis. SETTING: Primary care or referral center. PARTICIPANTS: Adults between
      ages 27 and 78 years (N=74) were tested before starting a 12-month lifestyle
      intervention. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The visual
      analog scale questionnaire was used to assess expectations and readiness (ie,
      intentions, conviction, and self-confidence) to modify the PA level and eating
      habits. The PA level was assessed with a pedometer and eating habits with a
      questionnaire. Analyses were stratified by the age group: <60 years old versus
      >=60 years old. RESULTS: Body mass loss expectations in terms of goal (-22.9% vs 
      17.9% of the current body mass; P=.04), acceptable (-15.6% vs -9.4%; P=.01), and
      failure (-7.6% vs -3.8%; P=.05) in future body mass loss were all greater for the
      younger group. Despite no significant age group difference in the initial PA
      level and eating habits, the youngest group had a greater intention to increase
      the PA level (89% vs 81%; P=.004) and to eat healthier (90% vs 85%; P=.001).
      Finally, the PA level and the consumption of fruits and vegetables, but not body
      mass, were associated with intentions or self-confidence to make some lifestyle
      modifications within age groups. CONCLUSIONS: In individuals at high risk for
      diabetes, increasing age is associated with lower expectations and reduced
      readiness with regard to lifestyle modifications. Thus, age should be considered
      when planning a lifestyle modification program.

PMID- 22475057
TI  - From "wheelchair circuit" to "wheelchair assessment instrument for people with
      multiple sclerosis": reliability and validity analysis of a test to assess
      driving skills in manual wheelchair users with multiple sclerosis.
AB  - OBJECTIVES: To assess the reliability and validity of the Wheelchair Assessment
      Instrument for people with Multiple Sclerosis (WAIMS), a test to measure driving
      skills in manual wheelchair users with multiple sclerosis (MS). DESIGN: Three
      test trials per subject were conducted by 2 raters to examine reliability (inter-
      and intrarater) and validity (concurrent and construct). SETTING: A national
      multiple sclerosis rehabilitation center. PARTICIPANTS: Convenience sample of
      manual wheelchair users with MS (n=50), participating in an inpatient or
      outpatient rehabilitation program in a national multiple sclerosis center.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The WAIMS consists of 8
      items and results in 3 final test scores: ability sum score, performance time sum
      score, and covered distance. These 3 scores are used to calculate inter- and
      intrarater reliability, concurrent validity, and construct validity. Concerning
      validity, the test scores on the WAIMS are compared with (1) the Belgian medical
      prescription of a wheelchair on the item d445 (hand and arm use), based on the
      International Classification of Functioning, Disability and Health, (2) the
      Expanded Disability Status Scale, and (3) the mobility (wheelchair) item of the
      FIM. RESULTS: Intrarater reliability was found to be higher than interrater
      reliability. Except for the interrater reliability of the ability sum score, all
      intraclass correlation coefficients met our standard of 0.80. Concurrent validity
      was rather low, but construct validity showed that the WAIMS is a valid
      instrument to assess driving skills in manual wheelchair users with MS.
      CONCLUSIONS: The WAIMS is a promising tool to assess driving skills in manual
      wheelchair users with MS, but it needs some refinements and future studies to
      confirm this statement.

PMID- 22475058
TI  - Smallest real difference of 2 instrumental activities of daily living measures in
      patients with chronic stroke.
AB  - OBJECTIVE: To estimate the smallest real difference (SRD) values of 2
      instrumental activities of daily living measures (the Nottingham Extended
      Activities of Daily Living [NEADL] and the Frenchay Activities Index [FAI]) in
      patients with chronic stroke. DESIGN: Test-retest reliability study. SETTING:
      Physical rehabilitation units of 5 hospitals. PARTICIPANTS: Chronic stroke
      patients (N=52; 37 men, 15 women) who were discharged from the hospital for more
      than 6 months. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Both
      measures were administered twice about 2 weeks apart to participants. The SRD was
      calculated on the basis of standard error of measurement: SRD = 1.96 * ?2 *
      Standard error of measurement. SRD% (the value of SRD divided by total score of a
      measure) was used to compare measurement errors across both measures.
      Reproducibility between successive measurements of the measures was investigated
      with intraclass correlation coefficients (ICCs). RESULTS: The SRD (SRD%) values
      of the NEADL and the FAI were 12.0 (21.1%) and 6.7 (14.9%), respectively. Test
      retest reproducibility of both measures was high (ICC: NEADL=.89, FAI=.89).
      CONCLUSIONS: Because of substantial SRD values of the NEADL and the FAI,
      prospective users should be cautious in using both measures to detect real change
      for a single subject.

PMID- 22475059
TI  - Clozapine is gold standard, but questions remain.

PMID- 22475060
TI  - Summary of current knowledge of the size and spatial distribution of the horse
      population within Great Britain.
AB  - BACKGROUND: Robust demographic information is important to understanding the risk
      of introduction and spread of exotic diseases as well as the development of
      effective disease control strategies, but is often based on datasets collected
      for other purposes. Thus, it is important to validate, or at least cross
      reference these datasets to other sources to assess whether they are being used
      appropriately. The aim of this study was to use horse location data collected
      from different contributing industry sectors ("Stakeholder horse data") to
      calibrate the spatial distribution of horses as indicated by owner locations
      registered in the National Equine Database (the NED). RESULTS: A conservative
      estimate for the accurately geo-located NED horse population within GB is
      approximately 840,000 horses. This is likely to be an underestimate because of
      the exclusion of horses due to age or location criteria. In both datasets, horse
      density was higher in England and Wales than in Scotland. The high density of
      horses located in urban areas as indicated in the NED is consistent with previous
      reports indicating that owner location cannot always be viewed as a direct
      substitute for horse location. Otherwise, at a regional resolution, there are few
      differences between the datasets. There are inevitable biases in the stakeholder
      data, and leisure horses that are unaffiliated to major stakeholders are not
      included in these data. Despite this, the similarity in distributions of these
      datasets is re-assuring, suggesting that there are few regional biases in the
      NED. CONCLUSIONS: Our analyses suggest that stakeholder data could be used to
      monitor possible changes in horse demographics. Given such changes in horse
      demographics and the advantages of stakeholder data (which include annual updates
      and accurate horse location), it may be appropriate to use these data for future
      disease modelling in conjunction with, if not in place of the NED.

PMID- 22475062
TI  - Experimental study on pulmonary cryoablation in a porcine model of normal lungs.
AB  - Objective of this study is to analyze the range of necrosis after using different
      freezing times and freeze-thaw cycles during percutaneous cryosurgery, in order
      to create a suggestion for optimizing the technique for lung cryoablation. Six
      healthy pigs were given a CT scan and histological investigation after
      percutaneous cryosurgery on both lungs. Three cryoprobes were inserted into both
      the left and right lungs of each pig, respectively. Cryoablation was performed
      with two cycles of an active 10-minute freezing using argon in the left lung,
      each freeze followed by an active 5-minute thaw using helium. In contrast to the
      left lung cryoablation, the right lungs underwent 3 cycles of freeze/thaw, the
      first and second cycles consisted of an active 5-minute freezing followed by an
      active 5-minute thaw, and the third cycle of 10-minute freezing and an active 5
      minute thaw. The CT imaging change of an ice ball was continuously observed. The
      lung tissues were taken 4 hours after cryosurgery on day 3 and on day 7,
      respectively, for pathological observation. One pig presented acute symptoms
      including bradycardia and hypothermia 30 minutes after cryosurgery, and died  4
      hours after the freezing, and the other 5 pigs experienced a weak condition for 4
      6 hours and then exhibited relatively normal behavior and regularly took food.
      The freezing area (ice ball) on CT imaging during the cryoablation grew gradually
      in relation to the increase over time, and along with the increase in the number
      of cycles. The size of the cryolesion on the lung samples became larger than the
      ice ball during cryosurgery, regardless of whether 2 or 3 freeze-thaw cycles were
      performed. The area of necrosis histologically gradually increased for the time
      being. Percutaneous cryosurgery on the lung can achieve complete ablation of
      targeted tissue. Three freeze-thaw cycles are recommended, and the range of
      cryoablation may not be mandatory "1 cm safe border" during cryosurgery in order
      to avoid harming the organ and tissue which is close to the cancer. Correct use
      of the technique is especially important to treat the lung neoplasms, especially
      the malignant tumors, which are close to the heart and large vessels.

PMID- 22475061
TI  - Reductively responsive siRNA-conjugated hydrogel nanoparticles for gene
      silencing.
AB  - A critical need still remains for effective delivery of RNA interference (RNAi)
      therapeutics to target tissues and cells. Self-assembled lipid- and polymer-based
      systems have been most extensively explored for transfection with small
      interfering RNA (siRNA) in liver and cancer therapies. Safety and compatibility
      of materials implemented in delivery systems must be ensured to maximize
      therapeutic indices. Hydrogel nanoparticles of defined dimensions and
      compositions, prepared via a particle molding process that is a unique off-shoot
      of soft lithography known as particle replication in nonwetting templates
      (PRINT), were explored in these studies as delivery vectors. Initially, siRNA was
      encapsulated in particles through electrostatic association and physical
      entrapment. Dose-dependent gene silencing was elicited by PEGylated hydrogels at
      low siRNA doses without cytotoxicity. To prevent disassociation of cargo from
      particles after systemic administration or during postfabrication processing for
      surface functionalization, a polymerizable siRNA pro-drug conjugate with a
      degradable, disulfide linkage was prepared. Triggered release of siRNA from the
      pro-drug hydrogels was observed under a reducing environment while cargo
      retention and integrity were maintained under physiological conditions. Gene
      silencing efficiency and cytocompatibility were optimized by screening the amine
      content of the particles. When appropriate control siRNA cargos were loaded into
      hydrogels, gene knockdown was only encountered for hydrogels containing
      releasable, target-specific siRNAs, accompanied by minimal cell death. Further
      investigation into shape, size, and surface decoration of siRNA-conjugated
      hydrogels should enable efficacious targeted in vivo RNAi therapies.

PMID- 22475063
TI  - CyberKnife radiosurgery for the treatment of orbital metastases.
AB  - Purpose of this study is to evaluate radiographic therapy response, clinical
      outcome and adverse effects of CyberKnife radiosurgery in patients suffering from
      orbital metastases. Sixteen orbital metastases originating from different solid
      cancers in fourteen patients were treated by single fraction CyberKnife
      radiosurgery. Radiographic response and clinical outcome were evaluated. The
      treated tumor volume ranged from 0.2 to 35 cm3 (median 2.3 cm3, mean 7.0 cm3, SD
      6 10.4 cm3, CI 0.9-9.4 cm3). The prescription dose ranged from 16.5-21 Gy (median
      18 Gy, mean 18.2 Gy, SD 6 1.2 Gy, CI 17.0-18.4 Gy). A no change situation was
      observed in nine lesions, partial remission in four as well as complete remission
      in one metastasis. Tumor growth was stabilized or regressive following CyberKnife
      therapy in 87% of the cases. Recurrence was observed in two cases (13%). Before
      therapy, three patients suffered from visual disturbance and five patients
      reported diplopia. Six patients had no initial symptoms. After therapy, one
      patient indicated improvement of the present visual deficit and two patients no
      change. Out of the two patients with persistent diplopia, two reported
      improvement after therapy and three no change. No progression of symptoms was
      noted in any of the cases. Fourteen out of sixteen treated lesions were stable or
      regressive following CyberKnife radiosurgery (87%). As no serious adverse effects
      were reported in this series, CyberKnife therapy was shown to be of great value
      for local management of orbital metastases.

PMID- 22475064
TI  - BNNT-mediated irreversible electroporation: its potential on cancer cells.
AB  - Irreversible lethal electroporation (IRE) is a new non-thermal ablation modality
      that uses short pulses of high amplitude static electric fields (up 1000 V/cm) to
      create irreversible pores in the cell membrane, thus, causing cell death.
      Recently, IRE has emerged as a promising clinical modality for cancer disease
      treatment. Here, we investigated the responses of tumour human HeLa cells when
      subjected to IRE in the presence of BNNTs. These consist of tiny tubes of B and N
      atoms (arranged in hexagons) with diameters ranging from a 1 to 3 nanometres and
      lengths < 2 MUm. BNNTs have attracted wide attention because of their unique
      electrical properties. We speculate that BNNTs, when interacting with cells
      exposed to static electrical fields, amplify locally the electric field, leading
      to cell death. In this work, electroporation assays were performed with a
      commercial electroporator using the cell- specific protocol suggested by the
      supplier (exponential decay wave, time constant 20 ms) with the specific aim to
      compare IRE in absence and in presence of BNNTs. We observed that BNNTs have the
      capacity to decrease substantially the voltage required for IRE. When cells were
      pulsed at 800 V/cm, we observed a 2,2-fold reduction in cell survival in the
      presence of BNNTs compared to controls. We conclude that the death of the tumour
      cells exposed to IRE is strongly enhanced in the presence of BNNTs, indicating
      their potential therapeutic application.

PMID- 22475065
TI  - Targeting liposomal nanomedicine  to cancer therapy.
AB  - Drug delivery systems (DDS) are designed to improve the pharmacological and
      therapeutic effect. In the past few decades, there are some problems that impeded
      applications of particulate DDS have been resolved, with several DDS formulations
      of anticancer now approved for clinical use. Liposomal nanoparticles (LNs)
      encapsulating therapeutic agents have been recognized as one of the most advanced
      classes of DDS. Liposomal nanoparticles (LNs) could encapsulate both conventional
      anticancer drugs and the new genetic drugs with several properties such as high
      drug-to-lipid ratio, excellent retention of drug and a long circulation lifetime.
      These excellent properties of LNs have the potentials to offer new treatments in
      area of cancer therapy. Here, we will discuss recent advances in this field
      involving conventional anticancer drugs as well as the new genetic drugs.

PMID- 22475066
TI  - Analysis of a metalloporphyrin antioxidant mimetic (MnTE-2-PyP) as a
      radiomitigator: prostate tumor and immune status.
AB  - Due to radiation-induced immune depression and development of pathologies such as
      cancer, there is increasing urgency to identify radiomitigators that are
      effective when administered after radiation exposure. The main goal of this study
      was to determine the radiomitigation capacity of MnTE-2-PyP[Mn(III) tetrakis (N
      ethylpyridinium-2-yl) porphyrin], a superoxide dismutase (SOD) mimetic, and
      evaluate leukocyte parameters in spleen and blood. C57BL/6 mice were total-body
      exposed to 2 Gy gamma-rays (Co-60), i.e., well below a lethal dose, followed by
      subcutaneous implantation of 5 * 10(5) RM-9 prostate tumor cells and initiation
      of MnTE-2-PyP treatment (day 0); interval between each procedure was 1-2 h. The
      drug was administered daily (12 times). Tumor progression was monitored and
      immunological analyses were performed on a subset per group on day 12. Animals
      treated with MnTE-2-PyP alone had significantly slower tumor growth compared to
      mice that did not receive the drug (P < 0.05), while radiation alone had no
      effect. Treatment of tumor-bearing mice with MnTE-2-PyP alone significantly
      increased spleen mass relative to body mass; the numbers of splenic white blood
      cells (WBC) and lymphocytes (B and T), as well as circulating WBC, granulocytes,
      and platelets, were high compared to one of more of the other groups (P < 0.05).
      The results show that MnTE-2-PyP slowed RM-9 tumor progression and up-regulated
      immune parameters, but mitigation of the effects of 2 Gy total-body irradiation
      were minimal.

PMID- 22475067
TI  - Correlation of three different approaches of small bowel delineation and acute
      lower gastrointestinal toxicity in adjuvant pelvic intensity-modulated radiation
      therapy for endometrial cancer.
AB  - We investigate in this study the approach of small bowel delineation that would
      best correlate with acute lower GI toxicity during adjuvant intensity-modulated
      radiation therapy (IMRT) for endometrial cancer in this study. Thirty-two
      endometrial cancer patients (FIGO IB-IVA) were treated with postoperative pelvic
      IMRT to 48.2 +/- 6 3.1 Gy. The small bowel was delineated as separate loops,
      limited bowel space (BS), or an intestinal cavity (IC). The volume of the small
      bowel (VSB) in absolute volume or as the percentage of the total volume at
      various dose levels was obtained from the dose volume histograms (DVHs). Each
      patient's acute lower gastro-intestinal (GI) toxicity was assessed prospectively
      during the course of IMRT. After a median follow up of 19.6 months, the median
      survival, loco-regional control, progression-free-survival (PFS), and distant
      metastasis-free survival (DMFS) were 40.9 months, 81.2%, 62.5%, and 68.8%,
      respectively. Acute lower GI toxicity observed were of grade 0, 1, and 2 only:
      34.4%, 31.2%, and 34.4%, respectively. The difference in %VSB with the small
      bowel delineated as IC at 45 Gy (%VSB(IC45)) between grade 2 and grade 0 acute
      lower GI toxicity reached statistical significance upon linear regression
      analysis ( p = 0.0347). Thus, the proportion of small bowel contoured as IC in
      the high dose region can potentially be an important predictor for acute lower GI
      toxicity during and after postoperative pelvic IMRT.

PMID- 22475068
TI  - Helping alliance, retention, and treatment outcomes: a secondary analysis from
      the NIDA Clinical Trials Network Women and Trauma Study.
AB  - We examined the association between the therapeutic alliance and treatment
      outcomes among 223 women with posttraumatic stress disorder (PTSD) and substance
      use disorders who participated in a multisite clinical trial of group treatments
      for trauma and addictions in the United States throughout 2004 and 2005. General
      linear models indicated that women who received Seeking Safety, a cognitive
      behavioral treatment, had significantly higher alliance ratings than those in
      Women's Health Education, a control group. Alliance was related to significant
      decreases in PTSD symptoms and higher attendance in both interventions. Alliance
      was not related to substance use outcomes. Implications and limitations of the
      findings are discussed.

PMID- 22475069
TI  - Understanding drug-related mortality in released prisoners: a review of national
      coronial records.
AB  - BACKGROUND: The prisoner population is characterised by a high burden of disease
      and social disadvantage, and ex-prisoners are at increased risk of death
      following release. Much of the excess mortality can be attributed to an increased
      risk of unnatural death, particularly from drug overdose; however, relatively few
      studies have investigated the circumstances surrounding drug-related deaths among
      released prisoners. This study aimed to explore and compare the circumstances of
      death for those who died from accidental drug-related causes to those who died
      from all other reportable causes. METHODS: A nationwide search of the Australian
      National Coroners Information System (NCIS) was conducted to identify reportable
      deaths among ex-prisoners from 2000 to 2007. Using a structured coding form, NCIS
      records for these cases were interrogated to explore causes and circumstances of
      death. RESULTS: Coronial records for 388 deceased ex-prisoners were identified.
      Almost half of these deaths were a result of accidental drug-related causes
      (45%). The majority of accidental drug-related deaths occurred in a home
      environment, and poly-substance use at or around the time of death was common,
      recorded in 72% of drug-related deaths. Ex-prisoners who died of accidental drug
      related causes were on average younger and less likely to be Indigenous, born in
      Australia, married, or living alone at or around the time of death, compared with
      those who died from all other reportable causes. Evidence of mental illness or
      self-harm was less common among accidental drug-related deaths, whereas evidence
      of previous drug overdose, injecting drug use, history of heroin use and history
      of drug withdrawal in the previous six months were more common. CONCLUSIONS: Drug
      related deaths are common among ex-prisoners and often occur in a home (vs.
      public) setting. They are often associated with use of multiple substances at or
      around the time of death, risky drug-use patterns, and even among this markedly
      disadvantaged group, extreme social disadvantage. These findings reflect the
      complex challenges facing prisoners upon release from custody and indicate a need
      to consider drug overdose within the wider framework of ex-prisoner experiences,
      so that preventive programmes can be appropriately structured and targeted.

PMID- 22475070
TI  - Effects of ascorbic acid on in vitro culture of bovine preantral follicles.
AB  - The objective of this study was to evaluate the effects of adding ascorbic acid
      to the media for in vitro culture of cattle ovarian fragments and to determine
      their effects on growth activation and viability of early-stage follicles. The
      ovarian cortex was divided into small fragments; one fragment was immediately
      fixed (control) and the other fragments were cultured in minimum essential medium
      (MEM) supplemented or not with various doses of ascorbic acid. Ovarian tissue was
      processed for histology, transmission electron microscopy (TEM) and
      immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA).
      Compared with control fragments, the percentage of primordial follicles was
      reduced (p < 0.05) and the percentage of growing follicles had increased (p <
      0.05) in cultured cortical fragments, independent of the tested medium or
      incubation time. Furthermore, compared with control tissue, culture of ovarian
      cortex for 8 days reduced the percentages of healthy, viable follicles (p <
      0.05), but not when cultures were supplemented with 25, 50 or 100 MUg/ml of
      ascorbic acid. Ultrastructural and immunohistochemical analysis of 8 day cultured
      ovarian cortical fragments, however, showed the integrity and viability of
      follicles only when fragments were cultured in presence of 50 MUg/ml of ascorbic
      acid. In conclusion, this study demonstrated that addition of ascorbic acid to
      MEM at a concentration of 50 MUg/ml not only stimulates the activation of 8 day
      in vitro cultured cattle primordial follicles and subsequent growth of activated
      follicles, but also safeguards the viability of these early-stage follicles.

PMID- 22475071
TI  - Delayed recovery in patients with whiplash-associated disorders.
AB  - BACKGROUND: Prognosis of whiplash injury has been found to be related to a number
      of sociodemographic, treatment and clinical factors. In the current study, we
      attempt to identify several novel prognostic factors for delayed recovery in
      whiplash-associated disorders (WADs), using a validated and reliable measure of
      recovery. PATIENTS AND METHODS: Retrospective review of a large database of a
      national network of physiotherapy and rehabilitation service providers in Canada
      yielded 5581 individuals injured in motor vehicle collisions. Cases were grouped
      into 3 cohorts based on time lapsed between injury date and initial presentation.
      Acute (n=3075), early chronic (n=958) and chronic (n=1548) patient cohorts were
      compared regarding treatment outcome and relative distribution of 29 prognostic
      factors. Outcome was defined by a minimally important clinical change (10%) on a
      previously validated disability questionnaire between initial and discharge
      rehabilitation visits. RESULTS: Analysis demonstrated positive outcomes to be
      proportionally fewer in the chronic cohort (52.1%) relative to the early chronic
      (61.4%), which was in turn lower than the acute cohort (72.3%). Furthermore,
      individuals presenting with chronic pain were more likely to: (1) be female; (2)
      present with lower limb pain or nonorganic signs; (3) have returned to work; (4)
      have retained a lawyer; or (5) have undergone previous spinal surgery, and were
      less likely to: (1) present with neck or midback pain; (2) live in Ontario or
      Nova Scotia; or (3) have modified duties upon return to work. Acute, early
      chronic and chronic cohorts were also found to differ in the distribution of
      several other prognostic factors at initial clinical visit. CONCLUSIONS: Recovery
      in whiplash-associated disorder appears to be multifactorial with both medical
      and non-injury related factors influencing outcome. Further characterisation of
      these factors may prove invaluable in guiding future clinical treatment and
      referral practices.

PMID- 22475072
TI  - Effect of metformin and spironolactone therapy on OGTT in patients with
      polycystic ovarian syndrome - a retrospective analysis.
AB  - BACKGROUND: Metformin (an insulin sensitizer) and spironolactone (an
      antiandrogen) are both used for treatment of polycystic ovary syndrome. We
      analyzed the effect of 6 months of therapy with these drugs on body weight and
      glucose tolerance. RESULTS: This was a retrospective analysis of polycystic
      ovarian syndrome (PCOS) cases on treatment. There were 88 patients with PCOS-42
      were on metformin 1 g daily and 46 were taking spironolactone 50-75 mg daily. 21
      of 42 had abnormal glucose tolerance (AGT) in the metformin group and 13 of 46
      had AGT in the spironolactone group. Patients on metformin reported a greater
      reduction in body weight, whereas there was no change in body weight with
      spironolactone therapy (67.6-63.7 versus 59.6-59.2 kg). There was a significant
      reduction in the 1 and 2 h glucose and insulin levels with metformin therapy in
      those with AGT. However, fasting glucose increased in those with normal glucose
      tolerance. There was no change in either body weight or insulin levels with
      spironolactone. But, there was a significant reduction in both the 0 and 2 h
      glucose with spironolactone also in those with AGT. CONCLUSION: Spironolactone
      and metformin had similar effect in reducing the glucose levels in PCOS patients
      with AGT. PCOS patients with normal glucose tolerance had higher fasting plasma
      glucose at the end of 6 months of metformin therapy inspite of weight reduction.

PMID- 22475073
TI  - Role of transportation in the persuasion process: cognitive and affective
      responses to antidrug narratives.
AB  - This study examined transportation effects of first- and third-person narratives
      as well as the role of transportation in the persuasion process. In particular,
      the authors evaluated the role of transportation in affecting cognitive and
      affective responses. Last, they addressed the relation between (a) cognitive and
      affective responses and (b) antidrug expectancies. Participants were 500
      undergraduate students at a large northern university in the United Kingdom who
      were randomly assigned to 1 of 2 conditions: first- or third-person narratives on
      cocaine use. The results demonstrated that there was no difference between first-
      and third-person narratives in terms of transportation. However, overall, greater
      transportation was associated with more favorable cognitive responses, and more
      favorable cognitive response was associated with stronger anticocaine
      expectancies. In terms of affective responses, results indicated the mediating
      role of sadness and contentment in the association between transportation and
      anticocaine expectancies. In particular, increased transportation was associated
      with greater sadness and lower contentment. Lower sadness and contentment were
      associated with stronger anticocaine expectancies. Important theoretical and
      empirical implications are discussed.

PMID- 22475074
TI  - Synthesis and photophysical investigation of a series of push-pull
      arylvinyldiazine chromophores.
AB  - A new series of push-pull arylvinyldiazines has been efficiently prepared by
      aldol condensation between the appropriate methyldiazine and aromatic aldehyde.
      The optical absorption and emission properties of these chromophores were studied
      in different solvents and media. These compounds act as polarity sensors with a
      strong positive emission solvatochromism. This behavior suggests a highly polar
      emitting state, which is characteristic of compounds that undergo an internal
      charge transfer upon excitation. These molecules also exhibit halochromic
      properties and are potential colorimetric and luminescence pH sensors. The second
      order nonlinear properties have been investigated for some of the compounds, and
      large and positive MUbeta are obtained, in particular, for pyrimidine
      derivatives.

PMID- 22475075
TI  - Dibenzophosphapentaphenes: exploiting P chemistry for gap fine-tuning and
      coordination-driven assembly of planar polycyclic aromatic hydrocarbons.
AB  - A synthetic route to planar P-modified polycylic aromatic hydrocarbons (PAHs) is
      described. The presence of a reactive sigma(3),lambda(3)-P moiety within the
      sp(2)-carbon scaffold allows the preparation of a new family of PAHs displaying
      tunable optical and redox properties. Their frontier molecular orbitals (MOs) are
      derived from the corresponding phosphole MOs and show extended conjugation with
      the entire pi framework. The coordination ability of the P center allows the
      coordination-driven assembly of two molecular PAHs onto a Au(I) ion.

PMID- 22475077
TI  - Insect virus polyhedra, infectious protein crystals that contain virus particles.
AB  - High-resolution atomic structures have been reported recently for two types of
      viral polyhedra, intracellular protein crystals produced by ubiquitous insect
      viruses. Polyhedra contain embedded virus particles and function as the main
      infectious form for baculoviruses and cypoviruses, two distinct classes of
      viruses that infect mainly Lepitoptera species (butterflies and moths). Polyhedra
      are extremely stable and protect the virus particles once released in the
      environment. The extensive crystal contacts observed in the structures explain
      the remarkable stability of viral polyhedra and provide hints about how these
      crystals dissolve in the alkaline midgut, releasing embedded virus particles to
      infect feeding larvae. The stage is now set to answer intriguing questions about
      the in vivo crystallization of polyhedra, how virus particles are incorporated
      into polyhedra, and what determines the size and shape of the crystals. Large
      quantities of polyhedra can be obtained from infected larvae and polyhedra can
      also be produced using insect cell expression systems. Modified polyhedra
      encapsulating other entities in place of virus particles have potential
      applications as a means to stabilize proteins such as enzymes or growth factors,
      and the extremely stable polyhedrin lattice may provide a framework for future
      engineered micro-crystal devices.

PMID- 22475076
TI  - Choice of generic antihypertensive drugs for the primary prevention of
      cardiovascular disease--a cost-effectiveness analysis.
AB  - BACKGROUND: Hypertension is one of the leading causes of cardiovascular disease
      (CVD). A range of antihypertensive drugs exists, and their prices vary widely
      mainly due to patent rights. The objective of this study was to explore the cost
      effectiveness of different generic antihypertensive drugs as first, second and
      third choice for primary prevention of cardiovascular disease. METHODS: We used
      the Norwegian Cardiovascular Disease model (NorCaD) to simulate the
      cardiovascular life of patients from hypertension without symptoms until they
      were all dead or 100 years old. The risk of CVD events and costs were based on
      recent Norwegian sources. RESULTS: In single-drug treatment, all
      antihypertensives are cost-effective compared to no drug treatment. In the base
      case analysis, the first, second and third choice of antihypertensive were
      calcium channel blocker, thiazide and angiotensin-converting enzyme inhibitor.
      However the sensitivity and scenario analyses indicated considerable uncertainty
      in that angiotensin receptor blockers as well as, angiotensin-converting enzyme
      inhibitors, beta blockers and thiazides could be the most cost-effective
      antihypertensive drugs. CONCLUSIONS: Generic antihypertensives are cost-effective
      in a wide range of risk groups. There is considerable uncertainty, however,
      regarding which drug is the most cost-effective.

PMID- 22475078
TI  - Rationally designing safer anilines: the challenging case of 4-aminobiphenyls.
AB  - We describe how we have been able to design 4-aminobiphenyls that are
      nonmutagenic (inactive in the Ames test). No such 4-aminobiphenyls were known to
      us, but insights provided by quantum mechanical calculations have permitted us to
      design and synthesize some examples. Importantly, the quantum mechanical
      calculations could be combined with predictions of other properties of the
      compounds that contained the 4-aminobiphenyls so that these remained druglike.
      Having found compounds that are not active, the calculations can provide insight
      into which factors (electronic and conformational in this case) are important.
      The calculations provided SAR-like information that was able guide the design of
      further examples of 4-aminobiphenyls that are not active in the Ames test.

PMID- 22475079
TI  - Structure and catalytic mechanism of LigI: insight into the amidohydrolase
      enzymes of cog3618 and lignin degradation.
AB  - LigI from Sphingomonas paucimobilis catalyzes the reversible hydrolysis of 2
      pyrone-4,6-dicarboxylate (PDC) to 4-oxalomesaconate and 4-carboxy-2
      hydroxymuconate in the degradation of lignin. This protein is a member of the
      amidohydrolase superfamily of enzymes. The protein was expressed in Escherichia
      coli and then purified to homogeneity. The purified recombinant enzyme does not
      contain bound metal ions, and the addition of metal chelators or divalent metal
      ions to the assay mixtures does not affect the rate of product formation. This is
      the first enzyme from the amidohydrolase superfamily that does not require a
      divalent metal ion for catalytic activity. The kinetic constants for the
      hydrolysis of PDC are 340 s(-1) and 9.8 * 10(6) M(-1) s(-1) (k(cat) and
      k(cat)/K(m), respectively). The pH dependence on the kinetic constants suggests
      that a single active site residue must be deprotonated for the hydrolysis of PDC.
      The site of nucleophilic attack was determined by conducting the hydrolysis of
      PDC in (18)O-labeled water and subsequent (13)C nuclear magnetic resonance
      analysis. The crystal structures of wild-type LigI and the D248A mutant in the
      presence of the reaction product were determined to a resolution of 1.9 A. The C
      8 and C-11 carboxylate groups of PDC are coordinated within the active site via
      ion pair interactions with Arg-130 and Arg-124, respectively. The hydrolytic
      water molecule is activated by the transfer of a proton to Asp-248. The carbonyl
      group of the lactone substrate is activated by electrostatic interactions with
      His-180, His-31, and His-33.

PMID- 22475080
TI  - Biodegradation of the endogenous residue of activated sludge in a membrane
      bioreactor with continuous or on-off aeration.
AB  - The goal of this study was to determine the effect of a long sludge retention
      time on the biodegradation of the endogenous residue in membrane digestion units
      receiving a daily feed of sludge and operated under either aerobic or
      intermittently aerated (22 h off-2 h on) conditions. The mixed liquor for these
      experiments was generated in a 10.4 day sludge retention time membrane bioreactor
      fed with a synthetic and completely biodegradable influent with acetate as the
      sole carbon source. It had uniform characteristics and consisted of only two
      components, heterotrophic biomass X(H) and endogenous residue X(E). Membrane
      digestion unit experiments were conducted for 80 days without any sludge wastage
      except for some sampling. The dynamic behaviour of generation and consumption of
      filtered organic digestion products was characterized in the membrane digestion
      unit systems using three pore filter sizes. Results from this investigation
      indicated that the colloidal matter with size between 0.04 MUm and 0.45 MUm was
      shown to contain a recalcitrant fraction possibly composed of polysaccharides
      bound to proteins which accumulated in the membrane digestion unit under both
      conditions. Modelling the membrane digestion unit results by considering a first
      order decay of the endogenous residue allowed to determine values of the
      endogenous residue decay rate of 0.0065 and 0.0072 d(-1) under fully aerobic and
      intermittently aerated conditions, respectively. The effect of temperature on the
      endogenous decay rate was assessed for the intermittently aerated conditions in
      batch tests using thickened sludge from tests gave an endogenous decay rate
      constant of 0.0075 d(-1) at 20  degrees C and an Arrhenius temperature correction
      factor of 1.033.

PMID- 22475081
TI  - Molecular simulation of aqueous electrolyte solubility. 3. Alkali-halide salts
      and their mixtures in water and in hydrochloric acid.
AB  - We extend the osmotic ensemble Monte Carlo (OEMC) molecular simulation method
      (Moucka et al. J. Phys Chem. B 2011, 115, 7849-7861) for directly calculating the
      aqueous solubility of electrolytes and for calculating their chemical potentials
      as functions of concentration to cases involving electrolyte hydrates and mixed
      electrolytes, including invariant points involving simultaneous precipitation of
      several solutes. The method utilizes a particular semigrand canonical ensemble,
      which performs simulations of the solution at a fixed number of solvent
      molecules, pressure, temperature, and specified overall electrolyte chemical
      potential. It avoids calculations for the solid phase, incorporating available
      solid chemical potential data from thermochemical tables, which are based on well
      defined reference states, or from other sources. We apply the method to a range
      of alkali halides in water and to selected examples involving LiCl monohydrate,
      mixed electrolyte solutions involving water and hydrochloric acid, and invariant
      points in these solvents. The method uses several existing force-field models
      from the literature, and the results are compared with experiment. The calculated
      results agree qualitatively well with the experimental trends and are of
      reasonable accuracy. The accuracy of the calculated solubility is highly
      dependent on the solid chemical potential value and also on the force-field model
      used. Our results indicate that pairwise additive effective force-field models
      developed for the solution phase are unlikely to also be good models for the
      corresponding crystalline solid. We find that, in our OEMC simulations, each
      ionic force-field model is characterized by a limiting value of the total
      solution chemical potential and a corresponding aqueous concentration. For higher
      values of the imposed chemical potential, the solid phase in the simulation grows
      in size without limit.

PMID- 22475082
TI  - Elucidating the structure of poly(dopamine).
AB  - Herein we propose a new structure for poly(dopamine), a synthetic eumelanin that
      has found broad utility as an antifouling agent. Commercially available 3
      hydroxytyramine hydrochloride (dopamine HCl) was polymerized under aerobic,
      aqueous conditions using tris(hydroxymethyl)aminomethane (TRIS) as a basic
      polymerization initiator, affording a darkly colored powder product upon
      isolation. The polymer was analyzed using a variety of solid state spectroscopic
      and crystallographic techniques. Collectively, the data showed that in contrast
      to previously proposed models, poly(dopamine) is not a covalent polymer but
      instead a supramolecular aggregate of monomers (consisting primarily of 5,6
      dihydroxyindoline and its dione derivative) that are held together through a
      combination of charge transfer, pi-stacking, and hydrogen bonding interactions.

PMID- 22475083
TI  - The effect of watchful waiting compared to immediate test ordering instructions
      on general practitioners' blood test ordering behaviour for patients with
      unexplained complaints; a randomized clinical trial (ISRCTN55755886).
AB  - BACKGROUND: Immediate blood testing for patients presenting with unexplained
      complaints in family practice is superfluous from a diagnostic point of view.
      However, many general pracitioners (GPs) order tests immediately. Watchful
      waiting reduces the number of patients to be tested and the number of false
      positive results. The objectives of this study are: to determine the feasibility
      of watchful waiting compared to immediate test ordering; to determine if a
      special quality improvement strategy can improve this feasibility; and to
      determine if watchful waiting leads to testing at a later time. METHODS: The
      study is a cluster-randomized clinical trial with three groups, on blood test
      ordering strategies in patients with unexplained complaints. GPs in group one
      were instructed to order tests immediately and GPs in group two to apply a
      watchful waiting approach. GPs in group three received the same instruction as
      group two, but they were supported by a systematically designed quality
      improvement strategy. A total of 498 patients with unexplained complaints from 63
      practices of Dutch GPs participated. We measured: the percentage of patients for
      whom tests were ordered and number of tests ordered at the first consultation;
      performance on the strategy's performance objectives (i.e., ordering fewer tests
      and specific communication skills); the number of tests ordered after four weeks;
      and GP and patient characteristics. RESULTS: Immediate test ordering proved
      feasible in 92% of the patients; watchful waiting in 86% and 84%, respectively,
      for groups two and three. The two watchful waiting groups did not differ
      significantly in the achievement of any of the performance objectives. Of the
      patients who returned after four weeks, none from group one and six from the two
      watchful waiting groups had tests ordered for them. CONCLUSIONS: Watchful waiting
      is a feasible approach. It does not lead to testing immediately afterwards.
      Furthermore, watchful waiting was not improved by the quality improvement
      strategy. TRIAL REGISTRATION:  CLINICAL TRIAL REGISTRATION: ISRCTN55755886.

PMID- 22475084
TI  - Are infertility treatments a potential risk factor for cancer development?
      Perspective of 30 years of follow-up.
AB  - The aim of the present study was to evaluate the possible risk for cancer
      development in infertile women with over 30 years of follow-up. Cancer
      development was assessed through linkage with the National Cancer Registry
      updated to 31 December 2005 in a cohort of 2431 women who were treated for
      infertility at the Sheba Medical Center in Israel during the period 1964-1974 and
      contributed more than 84,000 women years of follow-up. Standardized incidence
      ratios (SIR) were calculated between the observed cancer cases and the expected
      cancer rates in the general population. The mean age at the end of follow-up was
      62.7 years. Eighteen cases of ovarian cancer were observed as compared to 18.1
      expected (SIR = 1.0; 95% CI = 0.59-1.57). For breast cancer, 153 cases were
      observed as compared to 131.9 expected (SIR = 1.16; 95% CI = 0.98-1.36), and for
      endometrial cancer, 30 cases were observed as compared to 17.8 expected cases
      (SIR = 1.69; 95% CI = 1.14-2.41). No excess risk associated with exposure to
      gonadotropins was observed. Infertility was found to be associated with
      significant increased risk for endometrial cancer and borderline increased risk
      for breast cancer. Ovarian cancer risk was not found to be elevated. No
      significant excess risk was associated with treatment with ovulation induction.

PMID- 22475085
TI  - Complement dependent cytotoxicity in chronic lymphocytic leukemia: ofatumumab
      enhances alemtuzumab complement dependent cytotoxicity and reveals cells
      resistant to activated complement.
AB  - Complement dependent cytotoxicity (CDC) is an important mechanism of action for
      monoclonal antibodies (mAbs) used in the treatment of chronic lymphocytic
      leukemia (CLL). We hypothesized that alemtuzumab (ALM) mediated CDC would be
      increased by the addition of ofatumumab (OFA). CLL cells from 21 previously
      untreated patients with progressive disease were tested in vitro for mAb binding,
      complement activation and CDC. The subpopulation of CDC resistant CLL cells was
      examined for levels of C3b and C5b-9 binding, and expression of complement
      regulatory proteins. OFA significantly increased complement activation and CDC in
      ALM-treated CLL cells, suggesting that combining ALM and OFA could improve
      clinical outcome in patients with CLL. Approximately 10% of CLL cells were
      resistant to CDC because of lower levels of complement activation or decreased
      cytotoxicity of activated complement. Improvement of clinical responses will
      require determining the mechanisms of CDC resistance and developing methods to
      overcome this problem.

PMID- 22475086
TI  - Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by
      controlled microfluidic formulation.
AB  - The discovery of potent new materials for in vivo delivery of nucleic acids
      depends upon successful formulation of the active molecules into a dosage form
      suitable for the physiological environment. Because of the inefficiencies of
      current formulation methods, materials are usually first evaluated for in vitro
      delivery efficacy as simple ionic complexes with the nucleic acids (lipoplexes).
      The predictive value of such assays, however, has never been systematically
      studied. Here, for the first time, by developing a microfluidic method that
      allowed the rapid preparation of high-quality siRNA-containing lipid
      nanoparticles (LNPs) for a large number of materials, we have shown that gene
      silencing assays employing lipoplexes result in a high rate of false negatives
      (~90%) that can largely be avoided through formulation. Seven novel materials
      with in vivo gene silencing potencies of >90% at a dose of 1.0 mg/kg in mice were
      discovered. This method will facilitate the discovery of next-generation reagents
      for LNP-mediated nucleic acid delivery.

PMID- 22475087
TI  - Group hypnotherapy versus group relaxation for smoking cessation: an RCT study
      protocol.
AB  - BACKGROUND: A significant number of smokers would like to stop smoking. Despite
      the demonstrated efficacy of pharmacological smoking cessation treatments, many
      smokers are unwilling to use them; however, they are inclined to try alternative
      methods. Hypnosis has a long-standing reputation in smoking cessation therapy,
      but its efficacy has not been scientifically proven. We designed this randomised
      controlled trial to evaluate the effects of group hypnosis as a method for
      smoking cessation, and we will compare the results of group hypnosis with group
      relaxation. METHODS/DESIGN: This is a randomised controlled trial (RCT) to
      compare the efficacy of a single session of hypnosis with that of relaxation
      performed in groups of 8-15 smokers. We intend to include at least 220
      participants in our trial. The inclusion criteria include smoking at least 5
      cigarettes per day, not using other cessation methods and being willing to quit
      smoking. The intervention is performed by a trained hypnotist/relaxation
      therapist. Both groups first receive 40 min of mental preparation that is based
      on motivational interviewing. Then, a state of deep relaxation is induced in the
      hypnosis condition, and superficial relaxation is induced in the control
      condition. Suggestions are made in the hypnosis condition that aim to switch the
      mental self-image of the participants from that of smokers to that of non
      smokers. Each intervention lasts for 40 min. The participants also complete
      questionnaires that assess their smoking status and symptoms of depression and
      anxiety at baseline, 2 weeks and 6 months post-intervention. In addition, saliva
      samples are collected to assess cotinine levels at baseline and at 6 months post
      intervention. We also assess nicotine withdrawal symptoms at 2 weeks post
      intervention. DISCUSSION: To the best of our knowledge, this RCT is the first to
      test the efficacy of group hypnosis versus group relaxation. Issues requiring
      discussion in the outcome paper include the lack of standardisation of hypnotic
      interventions in smoking cessation, the debriefing of the participants, the
      effects of group dynamics and the reasons for dropouts. TRIAL REGISTRATION:
      Current Controlled Trials, ISRCTN72839675.

PMID- 22475088
TI  - Alcohol use and social adjustment in adolescence: a longitudinal, multilevel
      study.
AB  - The study examined to what extent alcohol use among Dutch adolescents (1,421
      adolescents, aged 12-16) was related to sociability and whether the social
      context affects this association. Data were based on self-reports and peer
      reports during 2005 and 2006. The results indicated that in contrast to previous
      assumptions, alcohol use did not predict changes in subsequent sociability. The
      findings also did not support the idea of curvilinear effects of alcohol use. In
      addition, the proportion of peers in class who drank had no effect on this
      association. Limitations and directions for future research are given.

PMID- 22475089
TI  - Drug-loaded PLGA nanoparticles for oral administration: fundamental issues and
      challenges ahead.
AB  - Drug-loaded polylactide-co-glycolide (PLGA) nanoparticles have been extensively
      studied and have a practical impact on drug delivery. Many PLGA-based
      nanoformulations have reached different stages of preclinical development;
      however, they present distinct challenges for researchers. This review discusses
      some of the challenges and issues involved in selecting drug and polymer
      combinations for encapsulation, aggregation of nanoparticles during
      characterization in in vitro studies, sterilization, and long-term stability of
      drug-loaded nanoparticles. We include recommendations to overcome these
      challenges.

PMID- 22475090
TI  - Prospective study of family adversity and maladaptive parenting in childhood and
      borderline personality disorder symptoms in a non-clinical population at 11
      years.
AB  - BACKGROUND: Retrospective studies have consistently indicated an association
      between maladaptive parenting and borderline personality disorder (BPD). This
      requires corroboration with prospective, longitudinal designs. We investigated
      the association between suboptimal parenting and parent conflict in childhood and
      BPD symptoms in late childhood using a prospective sample. METHOD: A community
      sample of 6050 mothers and their children (born between April 1991 and December
      1992) were assessed. Mothers' family adversity was assessed during pregnancy and
      parenting behaviours such as hitting, shouting, hostility and parent conflict
      across childhood. Intelligence quotient (IQ) and DSM-IV Axis I diagnoses were
      assessed at 7-8 years. Trained psychologists interviewed children at 11 years
      (mean age 11.74 years) to ascertain BPD symptoms. RESULTS: After adjustment for
      confounders, family adversity in pregnancy predicted BPD probable 1 to 2
      adversities: odds ratio (OR)=1.34 [95% confidence interval (CI) 1.01-1.77]; >2
      adversities: OR 1.99 (95% CI 1.34-2.94) and definite 1 to 2 adversities: OR 2.48
      (95% CI 1.01-6.08) symptoms. Each point increase in the suboptimal parenting
      index predicted BPD probable: OR 1.13 (95% CI 1.05-1.23) and definite: OR 1.28
      (95% CI 1.03-1.60) symptoms. Parent conflict predicted BPD probable: OR 1.19 (95%
      CI 1.06-1.34) and definite: OR 1.42 (95% CI 1.06-1.91) symptoms. Within the path
      analysis, the association between suboptimal parenting and BPD outcome was
      partially mediated by DSM-IV diagnoses and IQ at 7-8 years. CONCLUSIONS: Children
      from adverse family backgrounds, who experience suboptimal parenting and more
      conflict between parents, have poor cognitive abilities and a DSM-IV diagnosis,
      are at increased risk of BPD symptoms at 11 years.

PMID- 22475091
TI  - Oocyte genome cloning used in biparental bovine embryo reconstruction.
AB  - Oocyte genome cloning is a method by which haploid maternal embryos are obtained
      in such a way that parthenogenetic haploid blastomeres from these embryos can be
      considered as a clone of the original gamete. Our objective was to generate
      oocyte genome replicates and use them to reconstruct biparental embryos by fusion
      with haploid male hemizygotes. Furthermore, we generated biparental homogeneous
      transgene-expressing embryos using parthenogenetic haploid blastomeres that
      expressed a transgene (EGFP). In the first experiment, parthenogenetic haploid
      embryos were generated by incubation of oocytes in ionomycin and 6
      dimethylaminopurine (DMAP) with a 3 h interval to permit their second polar body
      extrusion. The cleavage rate was 87.3%. To generate transgene-expressing
      blastomeres, activated oocytes were injected with pCX-EGFP-liposome complexes 3 h
      post ionomycin exposure, resulting in a cleavage rate of 84.4%. In the second
      experiment, haploid parthenogenetic blastomeres that were positive or negative
      for EGFP expression were used to reconstruct biparental embryos. Cleavage and
      blastocyst rates for the reconstructed embryos were 78.4% and 61.1% and 10.8% and
      8.4%, using EGFP-positive or -negative blastomeres, respectively (P < 0.05). All
      of the reconstructed embryos showed EGFP expression, with 96.6% of them showing
      homogenic expression. Oct-4 expression in the reconstructed blastocysts displayed
      a similar pattern as IVF-blastocyst controls. In conclusion, our results proved
      that it is possible to use oocyte genome replicates to reconstruct biparental
      bovine embryos and that this technique is efficient to generate homogeneous
      transgene-expressing embryos.

PMID- 22475092
TI  - A comparative study of bipolar disorder and attention deficit hyperactivity
      disorder through the measurement of regional cerebral blood flow.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) and Bipolar Disorder (BPD) are
      two common neuropsychological disorders which are often present in a comorbid
      state. I used the results of cerebral blood flow studies made with Single Photon
      Emission Computer Tomography (SPECT), Positron Emission Tomography (PET) and
      Functional Magnetic Resonance Imaging (fMRI), to investigate a possible
      relationship between ADHD and BPD. The common areas of the brain involved in both
      BPD and ADHD appears to be the prefrontal cortex in its various components, the
      basal ganglia and possibly the cerebellum which, especially in the past, has been
      little studied by researchers in relation to ADHD and BPD. Among the differences
      the blood flow lateralization, present in BPD in states of altered mood, is
      evident with left hypoperfusion and right hyperperfusion during depression, the
      opposite in the case of manic state; in ADHD, the lateralization is less constant
      and of questionable interpretation. In BPD the involvement of a greater number of
      brain areas, especially the temporal lobe, is common. I advance the hypothesis
      that BPD progresses from ADHD secondary to expansion of perturbation in cerebral
      blood flow.

PMID- 22475093
TI  - IL-36 a new member of the IL-1 family cytokines.
AB  - Interleukin-36 (IL-36) is a pro-inflammatory cytokine which plays an important
      role in innate and adaptive immunity. IL-36 activates MAPK and NF-kB pathways and
      is produced by many different cells. This cytokine is a family member of
      interleukin-1 (IL-1) and plays an important role in the pathophysiology of
      several diseases. Here we summarise and review the new aspects of this important
      pro-inflammatory cytokine.

PMID- 22475094
TI  - Treadmill exercise improved adriamycin-induced nephropathy.
AB  - Adriamycin nephropathy (AN) or doxorubicin-induced chronic kidney disease (DRCKD)
      has several strengths as an experimental model of renal diseases involving
      glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Exercise has
      shown to be beneficial to many chronic diseases. We hypothesize that treadmill
      exercise may improve AN, and an investigation was carried out with the AN SD rat
      model. Treadmill exercise was conducted three times per week, each time for 30
      and 60 min. DR induced swelling of glomeruli, collagen deposition in the
      interstitium and renal cortex, and increased the serum levels of MDA, IL-6, PDGF
      BB, MMP-2, MMP-9, TGF-beta, p-PDGFR, uric acid, serum cholesterol, triglycerides,
      BUN, creatinine, blood platelet count, ratio of kidney to body weight, glomerular
      volume, and urinary BUN and protein. Conversely, levels of serum SOD, TNF-alpha,
      p-PI3K, p-Akt, albumin, WBC, RBC, and urinary creatinine were decreased.
      Treadmill exercise ameliorated most of these damaging effects, better outcome was
      found for the 60-min exercise training. Conclusively, the endurance exercise is
      more associated with the normalization of signaling expressions involving TGF
      beta, PDGF-BB, p-PDGFR, p-PI3K, and p-Akt, which may help CKD patients to restore
      cell survival, proliferation, and growth. As rehabilitation is a personalized
      medicine, an appropriate design to fit individual feasibility has to be well
      figured out.

PMID- 22475095
TI  - Early angiogenic response to shock waves in a three-dimensional model of human
      microvascular endothelial cell culture (HMEC-1).
AB  - The exact nature of shock wave (SW) action is not, as yet, fully understood,
      although a possible hypothesis may be that shock waves induce neoangiogenesis. To
      test this hypothesis, a three-dimensional (3D) culture model on Matrigel was
      developed employing a human microvascular endothelial cell line (HMEC-1) which
      was stimulated with low energy soft- focused SW generated by an SW lithotripter.
      After 12 hours we observed a statistically significant increase in capillary
      connections subsequent to shock-wave treatment in respect to the control group
      and a marked 3-hour down-regulation in genes involved in the apoptotic processes
      (BAX, BCL2LI, GADD45A, PRKCA), in cell cycle (CDKN2C, CEBPB, HK2, IRF1, PRKCA),
      oncogenes (JUN, WNT1), cell adhesion (ICAM-1), and proteolytic systems (CTSD,
      KLK2, MMP10). Our preliminary results indicate that microvascular endothelial
      cells in vitro quickly respond to SW, proliferating and forming vessel-like
      structures, depending on the energy level employed and the number of shocks
      released. The early decreased expression in the analysed genes could be
      interpreted as the first reactive response of the endothelial cells to the
      external stimuli and the prelude to the events characterizing the neo-angiogenic
      sequence.

PMID- 22475096
TI  - In vitro exposure of human osteoarthritic chondrocytes to ELF fields and new
      therapeutic application of musically modulated electromagnetic fields: biological
      evidence.
AB  - Osteoarthritis (OA) is the most frequently occurring rheumatic disease, caused by
      metabolic changes in chondrocytes, the cells that maintain cartilage. Treatment
      with electromagnetic fields (MF) produces benefits in patients affected by this
      pathology. Isolated human osteoarthritic (OA) chondrocytes were cultured in vitro
      under standard conditions or stimulated with IL-1beta or IGF-1, to mimic the
      imbalance between chondroformation and chondroresorption processes observed in OA
      cartilage in vivo. The cells were exposed for a specific time to extremely low
      frequency (ELF; 100-Hz) electromagnetic fields and to the Therapeutic Application
      of Musically Modulated Electromagnetic Fields (TAMMEF), which are characterized
      by variable frequencies, intensities, and waveforms. Using flow cytometry, we
      tested the effects of the different types of exposure on chondrocyte metabolism.
      The exposure of the cells to both systems enhances cell proliferation, does not
      generate reactive oxygen species, does not cause glutathione depletion or changes
      in mitochondrial transmembrane potential and does not induce apoptosis. This
      study presents scientific support to the fact that MF could influence OA
      chondrocytes from different points of view (viability, ROS production and
      apoptosis). We can conclude that both ELF and TAMMEF systems could be recommended
      for OA therapy and represent a valid non-pharmacological approach to the
      treatment of this pathology.

PMID- 22475097
TI  - Tissue distribution and metabolism of guanosine in rats following intraperitoneal
      injection.
AB  - Guanosine has long been known as an endogenous purine nucleoside deeply involved
      in the modulation of several intracellular processes, especially G-protein
      activity. More recently, it has been reported to act as an extracellular
      signaling molecule released from neurons and, more markedly, from astrocytes
      either in basal conditions or after different kinds of stimulation including
      hypoxia. Moreover, in vivo studies have shown that guanosine plays an important
      role as both a neuroprotective and neurotrophic agent in the central nervous
      system. Specific high-affinity binding sites for this nucleoside have been found
      on membrane preparations from rat brain. The present study was undertaken to
      investigate the distribution and metabolic profiles of guanosine after
      administering the nucleoside to gain a better understanding of the biological
      effects of this potential drug candidate. Rats were given an intraperitonal
      (i.p.) injection of 2, 4, 8 or 16 mg/kg of guanosine combined with 0.05% of
      [3H]guanosine. Plasma samples were collected 7.5, 15, 30, 60 and 90 min after the
      guanosine-mixture administration and analyzed by either a liquid scintillation
      counter or by HPLC connected to a UV and to an on-line radiochemical detector to
      measure the levels of guanosine and its metabolic products guanine, xanthine and
      uric acid. The levels of guanosine, guanine and xanthine were also measured in
      brain, lung, heart, kidney and liver tissue homogenates at the defined time
      points after the injection of 8 mg/kg of the guanosine-mixture. We found that the
      levels of radioactivity in plasma increased linearly in a dose- and time
      dependent manner. Guanosine was widely distributed in all tissues examined in the
      present study, at almost twice its usual levels. In addition, guanine levels
      dramatically increased in all the organs. Interestingly, enzymatic analysis of
      the plasma samples showed the presence of a soluble purine nucleoside
      phosphorylase, a key enzyme in the purine salvage pathway and nucleoside
      catabolism. Since guanosine has been shown to be neuroprotective and astrocytes
      have been reported to play critical roles in mediating neuronal survival and
      functions in different neurodegenerative disorders, we also performed uptake and
      release.

PMID- 22475098
TI  - Circulating cytokines present in the serum of peripheral arterial disease
      patients induce endothelial dysfunction.
AB  - Peripheral arterial disease (PAD) is a chronic condition caused by
      atherosclerosis and is a severe complication of type 2 diabetes (T2D). We
      hypothesised that chronic condition of arterial disease engenders inflammation
      and endothelial damage in response to circulating cytokines released in the blood
      stream of PAD patients. We explored the levels of circulating cytokines in PAD
      patients with and without diabetes by multiplex cytokine array compared with non
      PAD controls. Serum from PAD patients with or without diabetes showed high levels
      of VEGF, IFN-gamma, TNF-alpha, MCP-1, and EGF. VEGF levels correlated with TNF
      alpha and IFN-gamma, significantly. Endothelial cells (ECs) were exposed to the
      different altered cytokines to evaluate changes in cell growth, migration and
      tubule-like formation, displaying impairment on proliferation, migration and
      tubule formation. Our findings demonstrate that a set of cytokines is
      significantly increased in the serum of PAD patients. These cytokines act to
      induce endothelial dysfunction synergistically. VEGF strongly correlated with TNF
      alpha and IFN-gamma, opening new therapeutic perspectives.

PMID- 22475099
TI  - Concomitant evaluation of flow-mediated vasodilation and epicardial fat thickness
      in idiopathic deep venous thrombosis.
AB  - Flow mediated vasodilation (FMD) evaluates the endothelium-dependent
      vasodilation, is a reliable marker of arterial endothelial dysfunction and is
      related to coronary artery disease. Visceral fat predicts an unfavorable
      cardiovascular and metabolic risk profile in humans and echocardiographic
      assessment of epicardial fat (EF) is a reliable marker of visceral adiposity. We
      measured the FMD and EF thickness in 77 subjects, 38 without idiopathic deep vein
      thrombosis (DVT) (mean age 65.95 +/- 16.29 years) and 39 with idiopathic DVT
      (mean age 65.49 +/- 17.22 years). The purpose of this work is to investigate the
      presence of statistical association between FMD and DVT and between EF thickness
      and DVT. Furthermore, to account for possible atherosclerosis risk factor
      unbalances, comparison between FMD and DVT (and between EF and DVT) was assessed
      using a multivariate logistic regression model which included the following
      covariates: FMD, EF, age, sex, smoking and the presence of obesity. Subjects
      without DVT showed significant lower values of EF thickness (9.07 +/- 1.89 mm vs
      12.32 +/- 1.73 mm, p=0.005) and borderline-significant greater values of FMD
      (9.01 +/- 2.77 percent vs 7.47 +/- 5.37 percent, p=0.058) as compared to those
      with DVT. In conclusion, the data presented indicate that subjects affected by
      spontaneous deep vein thrombosis may have an impaired endothelium-dependent
      vasodilation, a marker of arterial endothelial dysfunction related to coronary
      artery disease, and an increased epicardial adipose tissue, a marker of
      cardiometabolic risk.

PMID- 22475100
TI  - Comparison of the primary stabilities of conical and cylindrical endosseous
      dental implants: an in-vitro study.
AB  - The aim of this study is to determine the differences in primary stability
      between conical and cylindrical dental implants. The insertion and removal
      torques were the parameters used to measure the primary stability of the
      implants. Ten conical and cylindrical dental implants were positioned in
      polyurethane foam blocks to simulate bone density classes D1, D2, D3 and D4. The
      insertion and removal torques were quantified using a digital torque gauge. The
      maximum insertion torque and the maximum removal torque measured for the D1 and
      D4 synthetic bone were significantly higher for the conical implants than the
      cylindrical implants. In this in-vitro model, conical implants show significantly
      higher primary stability than cylindrical implants for the D1 and D4 synthetic
      bone classes.

PMID- 22475101
TI  - Endocytosis and intracellular localisation of type 1 ribosome-inactivating
      protein saporin-s6.
AB  - Saporin-S6 is a single-chain ribosome-inactivating protein (RIP) that has low
      toxicity in cells and animals. When the protein is bound to a carrier that
      facilitates cellular uptake, the protein becomes highly and selectively toxic to
      the cellular target of the carrier. Thus, saporin-S6 is one of the most widely
      used RIPs in the preparation of immunoconjugates for anti-cancer therapy. The
      endocytosis of saporin-S6 by the neoplastic HeLa cells and the subsequent
      intracellular trafficking were investigated by confocal microscopy that utilises
      indirect immunofluorescence analysis and transmission electron microscopy that
      utilises a direct assay with gold-conjugated saporin-S6 and an indirect
      immunoelectron microscopy assay. Our results indicate that saporin-S6 was taken
      up by cells mainly through receptor-independent endocytosis. Confocal microscopy
      analysis showed around 30% co-localisation of saporin-S6 with the endosomal
      compartment and less than 10% co-localisation with the Golgi apparatus. The
      pathway identified by the immunofluorescence assay and transmission electron
      microscopy displayed a progressive accumulation of saporin-S6 in perinuclear
      vesicular structures. The main findings of this work are the following: i) the
      nuclear localisation of saporin-S6 and ii) the presence of DNA gaps resulting
      from abasic sites in HeLa nuclei after intoxication with saporin-S6.

PMID- 22475102
TI  - The gaseous messenger carbon monoxide is released from the eye into the
      ophthalmic venous blood depending on the intensity of sunlight.
AB  - Circadian and seasonal rhythms in daylight affect many physiological processes.
      In the eye, energy of intense visible light not only initiates a well-studied
      neural reaction in the retina that modulates the secretory function of the
      hypothalamus and pineal gland, but also activates the heme oxygenase (HO) to
      produce carbon monoxide (CO). This study was designed to determine whether the
      concentration of carbon monoxide (CO) in the ophthalmic venous blood changes
      depending on the phase of the day and differing extremely light intensity
      seasons: summer and winter. The concentration of CO in the venous blood flowing
      out from the nasal cavity, where heme oxygenase (HO) is expressed, but no
      photoreceptors, was used as a control. Sixteen mature males of a wild boar and
      pig crossbreed were used for this study. Samples of ophthalmic and nasal venous
      blood and systemic arterial and venous blood were collected repeatedly for two
      consecutive days during the longest days of the summer and the shortest days of
      the winter. The concentrations of CO in blood samples was measured using a
      standard addition method. During the longest days of the summer the concentration
      of CO in ophthalmic venous blood averaged 3.32 +/- 0.71 and 3.43 +/- 0.8 nmol/ml
      in the morning and afternoon, respectively, and was significantly higher than in
      the night averaging 0.89 +/- 0.12 nmol/ml (p<0.001). During the shortest day of
      the winter CO concentration in ophthalmic venous blood was 1.11 +/- 0.10 and 1.13
      +/- 0.14 nmol/ml during the light and nocturnal phase, respectively, and did not
      differ between phases, but was lower than in the light phase of the summer
      (p<0.01). The CO concentration in the control nasal venous blood did not differ
      between seasons and day phases and was lower than in ophthalmic venous blood
      during the summer (p<0.01) and winter (p<0.05). The results indicate that the
      gaseous messenger carbon monoxide is released from the eye into the ophthalmic
      venous blood depending on the intensity of sunlight.

PMID- 22475103
TI  - Pharmacological manipulation of the dopaminergic system affects wheel-running
      activity in differentially active mice.
AB  - The genetic factors involved in the regulation of physical activity are not well
      understood. The dopamine system has been implicated in the control of voluntary
      locomotion and wheel running (WR) in mice and is thus a likely candidate as a
      genetic/biological system important to the regulation of physical activity. This
      study evaluated the effects of four different dopaminergic acting drugs on WR in
      differentially active inbred strains of mice. High active C57L/J (n=7, 3
      controls, 4 experimental) and low active C3H/HeJ (n=8, 3 controls, 5
      experimental) were analyzed for baseline wheel-running indices of distance
      (km/day), duration (mins/day), and speed (m/min) for 21 days. Experimental mice
      received increasing doses over four days of each of the following drugs: SKF
      81297 (D1 agonist), SCH 23390 (D1 antagonist), GBR 12783 (DAT inhibitor), and
      AMPT (tyrosine hydroxylase inhibitor). Each drug dose response treatment was
      separated by three days of recovery (no drug injections). WR indices were
      monitored during drug treatments and during drug wash-out phases. SKF 81297
      significantly reduced (p=0.0004) WR in the C57L/J mice, but did not affect WR in
      the C3H/HeJ mice. GBR 12783 significantly increased (p=0.0005) WR in C3H/HeJ
      mice, but did not affect WR in C57L/J mice. Only duration (not overall WR) was
      significantly reduced in C57L/J mice in response to SCH 23390 (p=0.003) and AMPT
      (p=0.043). SCH 23390 (p=0.44) and AMPT (p=0.98) did not significantly affect WR
      in C3H/HeJ mice. These results suggest that genetic differences in dopamine
      signaling may play a role in the WR response to dopaminergic-acting drugs in
      inbred strains of mice. The high activity in the C57L/J strain appears most
      responsive to D1-like receptor acting drugs, while in the C3H/HeJ strain,
      dopamine re-uptake appears to have an influence on activity level.

PMID- 22475104
TI  - Corticosteroids provoke acute endothelial injury -- an ideal ground for
      thrombosis in multiple sclerosis.
AB  - Despite the effect corticosteroids exert on blood clotting and the irrefutable
      impact of intracranial sure decreasing shortly after lumbar puncture, a certain
      number of intracranial thromboses remain unexplained. Corticosteroids are useful
      in reducing the severity and duration of relapses of multiple sclerosis. Several
      questions emerge concerning the reasons behind thrombosis occurring so
      sporadically, not pertaining to any rule, the most important of which regard the
      location and timing. We developed this hypothesis as an obverse to chronic
      endothelial injury theory which, only partially explains atherosclerosis
      development. We followed Virchows classical triad of conditions which are
      believed to be connected to the development of thrombosis. Although
      corticosteroids affect more than vessel wall injury, component of Virchows triad
      that has been our narrowest interest is exactly vessel wall injury.

PMID- 22475105
TI  - ACTH and azathioprine: antiproteinuric and lipid-lowering effect in the course of
      idiopathic membranous glomerulonephritis.
AB  - Idiopathic membranous glomerulonephritis is a frequent cause of nephrotic
      syndrome and may have a variable course, from spontaneous remission to
      progression on renal failure. The therapy is based on alternating steroids and
      chlorambucil or cyclophosphamide (Ponticelli protocol) for six months. In absence
      of complete or partial remission after protocol, cyclosporine,
      adrenocorticotropic hormone, mycophenolate mofetil, rituximab can be used for
      potential therapy. We report here the case of a woman with idiopathic membranous
      glomerulonephritis unresponsive to the Ponticelli regimen and treated with
      adrenocorticotropic hormone in association with azathioprine, showing a dramatic
      decrease of proteinuria and beneficial effects on lipid profile. After 36 months,
      no relapse of disease has occurred. Although larger cohorts of patients are
      needed to evaluate the long-term effects, adrenocorticotropic hormone plus
      azathioprine in association could be a possible therapeutic option for
      unresponsive idiopathic membranous glomerulonephritis.

PMID- 22475106
TI  - Skeletal modifications in mucopolysaccharidoses: an overview.
AB  - The mucopolysaccharidoses (MPS) are a group of rare diseases characterized by
      deficiencies in different enzymes required for degradation of complex
      carbohydrates. The enzymatic deficiencies lead to lysosomal accumulation of
      dermatan sulphate, heparan sulphate, and keratan sulphate in different tissue
      resulting in multi-system complications. Six different principal types are
      described. Most MPS types, with the exception of MPS III, are associated with
      widespread skeletal abnormalities and joint disease. Authors analyzed clinical
      pathological and radiographical features of mucopolysaccharidoses focusing on
      pelvic and spine pathologies that generally limit activity and normal life so
      they have to be treated at the beginning of their manifestations in order to
      avoid major complication and improve quality of life.

PMID- 22475107
TI  - Adverse reaction to irrigation with povidone-iodine after deep-impacted, lower
      third molar extraction.
AB  - Povidone-iodine is most commonly used worldwide because of its germicidal
      activity, relatively low irritancy or toxicity and low cost. Frequently, povidone
      iodine is used as a topical antiseptic for treating and preventing wound
      infection. In rare cases skin irritation or iododerma-like eruption could
      represent possible adverse effects due to the oxidative effects of iodine and
      allergic hypersensitivity reaction. In this report we describe a case of a
      massive adverse reaction to the irrigation of surgical wound dehiscence with 10
      percent povidone-iodine solution after deep-impacted, lower third molar
      extraction. This reaction was related to a central neurotrophic reflex involving
      three trigeminal branches and probably due to peripheral chemical insult of
      mandible nerve. This adverse reaction determined a severe edema and diffuse skin
      lesions, involving the whole left side of the face mimicking an iododerma-like
      eruption. These violent symptoms were solved after 60 days. Furthermore, we
      report a small permanent skin scar in the zygomatic area and transient
      alterations of facial sensitivity on the affected side which completely
      disappeared in 6 months.

PMID- 22475108
TI  - Platelet-rich plasma improves wound healing in multiple myeloma bisphosphonate
      associated osteonecrosis of the jaw patients.
AB  - Bisphosphonates are drugs used to treat various metabolic and malignant bone
      diseases. In the past 10 years intravenous bisphosphonates have been associated
      with increased risk of osteonecrosis of the jaw (ONJ). The aim of the present
      study is to evaluate platelet-rich plasma (PRP) wound healing benefits in
      multiple myeloma (MM) patients who developed ONJ after surgical tooth extraction.
      The study included 7 patients, 2 males and 5 females. All individuals had been
      taking zoledronate or pamidronate followed by zoledronate for an average of 5
      years. Four subjects had only standard surgical debridement and sequestrectomy to
      treat the ONJ and three had additional autologous PRP. The patients were followed
      up for 3 months. The use of PRP to enhance wound healing and reduce bone exposure
      seems to be a good treatment protocol in ONJ MM subjects.

PMID- 22475109
TI  - Sclerostin concentrations in athletes: role of load and gender.
AB  - Bone mass is the net product of formation and resorption, which are closely
      regulated by the equilibrium between endogenous/exogenous factors. Sclerostin
      inhibits the Wnt canonical signaling and is considered an anti-anabolic factor.
      We compared sclerostin serum concentrations between genders in athletes belonging
      to different sport disciplines, characterized by a different weight-bearing, and
      in their sedentary counterparts in order to study the possible link between bone
      metabolism in athletes and its peripheral concentration. We also compared
      sclerostin levels with bone alkaline phosphatase activity, a marker of bone
      formation. Sixty-one elite athletes, belonging to weight-bearing (15 male rugby
      players, 11 male enduro racers, 8 female basketball players), high-impact (6 male
      tennis players, 8 female ice skaters), non weight-bearing sports (13 male
      cyclists) and 16 sedentary controls were enrolled. Higher levels of sclerostin
      were found in females. Sclerostin was higher in weight-bearing than in non-weight
      bearing disciplines in males. Significant inverse age-related correlation was
      found. Higher bone alkaline phosphatase activity was observed in females. The
      young adult elite athlete represents a peculiar physiologic model for studying
      sclerostin behavior: the applied load increased the marker concentrations,
      testifying a high bone turnover rate; however, a gender effect is evident.

PMID- 22475110
TI  - Adsorption of beta-casein-surfactant mixed layers at the air-water interface
      evaluated by interfacial rheology.
AB  - This work presents a detailed study of the dilational viscoelastic moduli of the
      adsorption layers of the milk protein beta-casein (BCS) and a surfactant at the
      liquid/air interface, over a broad frequency range. Two complementary techniques
      have been used: a drop profile tensiometry technique and an excited capillary
      wave method, ECW. Two different surfactants were studied: the nonionic
      dodecyldimethylphosphine oxide (C12DMPO) and the cationic
      dodecyltrimethylammonium bromide (DoTAB). The interfacial dilational elasticity
      and viscosity are very sensitive to the composition of protein-surfactant mixed
      adsorption layers at the air/water interface. Two different dynamic processes
      have been observed for the two systems studied, whose characteristic frequencies
      are close to 0.01 and 100 Hz. In both systems, the surface elasticity was found
      to show a maximum when plotted versus the surfactant concentration. However, at
      frequencies above 50 Hz the surface elasticity of BCS + C12DMPO is higher than
      the one of the aqueous BCS solution over most of the surfactant concentration
      range, whereas for the BCS + DoTAB it is smaller for high surfactant
      concentrations and higher at low concentrations. The BCS-surfactant interaction
      modifies the BCS random coil structure via electrostatic and/or hydrophobic
      interactions, leading to a competitive adsorption of the BCS-surfactant complexes
      with the free, unbound surfactant molecules. Increasing the surfactant
      concentration decreases the adsorbed proteins. However, the BCS molecules are
      rather strongly bound to the interface due to their large adsorption energy. The
      results have been fitted to the model proposed by C. Kotsmar et al. ( J. Phys.
      Chem. B 2009 , 113 , 103 ). Even though the model describes well the
      concentration dependence of the limiting elasticity, it does not properly
      describe its frequency dependence. 

PMID- 22475111
TI  - Reversibility of airway obstruction vs bronchodilatation: do we speak the same
      language?
AB  - Airway reversibility test (or bronchodilatation test) is performed routinely in
      the diagnosis of obstructive lung diseases. The results of this test may be
      helpful in the diagnosis and differential diagnosis of asthma and chronic
      obstructive pulmonary disease (COPD), but sometimes bring confusion.
      Unfortunately, the nomenclature used for test result is not uniform, which also
      leads to confusion. Next the reader will find an attempt to order the state of
      affairs and the introduction of a uniform nomenclature, which would be consistent
      with the logic and allow for unambiguous classification of reversibility test
      results to facilitate future decisions based on the differential diagnosis.

PMID- 22475112
TI  - Results from a blind and a non-blind randomised trial run in parallel: experience
      from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial.
AB  - BACKGROUND: The Estonian Postmenopausal Hormone Therapy (EPHT) Trial assigned
      4170 potential participants prior to recruitment to blind or non-blind hormone
      therapy (HT), with placebo or non-treatment the respective alternatives. Before
      having to decide on participation, women were told whether they had been
      randomised to the blind or non-blind trial. Eligible women who were still willing
      to join the trial were recruited. After recruitment participants in the non-blind
      trial (N = 1001) received open-label HT or no treatment, participants in the
      blind trial (N = 777) remained blinded until the end of the trial. The aim of
      this paper is to analyse the effect of blinding on internal and external validity
      of trial outcomes. METHODS: Effect of blinding was calculated as the hazard ratio
      of selected chronic diseases, total mortality and all outcomes. For analysing the
      effect of blinding on external validity, the hazard ratios from women recruited
      to the placebo arm and to the non-treatment arm were compared with those not
      recruited; for analysing the effect of blinding on internal validity, the hazard
      ratios from the blind trial were compared with those from the non-blind trial.
      RESULTS: The women recruited to the placebo arm had less cerebrovascular disease
      events (HR 0.43; 95% CI: 0.26-0.71) and all outcomes combined (HR 0.76; 95% CI:
      0.63-0.91) than those who were not recruited. Among women recruited or not
      recruited to the non-treatment arm, no differences were observed for any of the
      outcomes studied.Among women recruited to the trial, the risk for coronary heart
      disease events (HR 0.77; 95% CI: 0.64-0.93), cerebrovascular disease events (HR
      0.66; 95%CI: 0.47-0.92), and all outcomes combined (HR 0.82; 95% CI: 0.72-0.94)
      was smaller among participants in the blind trial than in the non-blind trial.
      There was no difference between the blind and the non-blind trial for total
      cancer (HR 0.95; 95% CI: 0.64-1.42), bone fractures (0.93; 95% CI: 0.74-1.16),
      and total mortality (HR 1.03; 95% CI: 0.53-1.98). CONCLUSIONS: The results from
      blind and non-blind trials may differ, even if the target population is the same.
      Blinding may influence both internal and external validity. The effect of
      blinding may vary for different outcome events. TRIAL REGISTRATION:
      [ISRCTN35338757].

PMID- 22475113
TI  - Insulator-metal transitions induced by electric field and photoirradiation in
      organic Mott insulator deuterated kappa-(BEDT-TTF)2Cu[N(CN)2]Br.
AB  - The Mott insulator-metal transition induced by an external stimulus such as
      electric field, pressure, chemical doping, or photoirradiation has received
      considerable attention because of the potential use in new optoelectronic
      functional devices. Here we report an abrupt Mott insulator-metal transition
      observed as a current jump in a molecular-based Mott insulator, namely,
      deuterated kappa-(BEDT-TTF)(2)Cu[N(CN)(2)]Br, where BEDT-TTF =
      bis(ethylenedithio)tetrathiafulvalene, upon application of a pulsed voltage of
      certain magnitude (threshold voltage). Furthermore, the threshold voltage needed
      for the transition is shown to be reduced by photoirradiation. Thus, the Mott
      insulator-metal transition can be controlled by a combination of an external
      electric field and photoirradiation.

PMID- 22475114
TI  - Challenges of pediatric surgical practice in Africa. Preface.

PMID- 22475115
TI  - Training and practice of pediatric surgery in Africa: past, present, and future.
AB  - The evolution and recognition of pediatric surgery as a specialty in Africa can
      be divided into 4 distinct phases, starting from early 1920s till the present.
      The pace of development has been quite variable in different parts of Africa.
      Despite all recent developments, the practice of pediatric surgery in Africa
      continues to face multiple challenges, including limited facilities, manpower
      shortages, the large number of sick children, disease patterns specific to the
      region, late presentation and advanced pathology, lack of pediatric surgeons
      outside the tertiary hospitals, and inadequate governmental support.
      Standardization of pediatric surgery training across the continent is advocated.
      Collaboration with well-established pediatric surgical training centers in Africa
      and other developed countries is necessary. The problems of delivery of pediatric
      surgical services need to be addressed urgently, if the African child is to have
      access to essential pediatric surgical services like his or her counterpart in
      the high-income parts of the world.

PMID- 22475116
TI  - Pediatric trauma care in Africa: the evolution and challenges.
AB  - Childhood trauma is one of the major health problems in the world. Although
      pediatric trauma is a global phenomenon in low- and middle-income countries, sub
      Saharan countries are disproportionally affected. We reviewed the available
      literature relevant to pediatric trauma in Africa using the MEDLINE database,
      local libraries, and personal contacts. A critical review of all cited sources
      was performed with an emphasis on the progress made over the past decades as well
      as the ongoing challenges in the prevention and management of childhood trauma.
      After discussing the epidemiology and spectrum of pediatric trauma, we focus on
      the way forward to reduce the burden of childhood injuries and improve the
      management and outcome of injured children in Africa.

PMID- 22475117
TI  - Surgical aspects of bacterial infection in African children.
AB  - Infections and their complications requiring surgical intervention are a frequent
      presentation in African children. Surgical site infection (SSI) is common with
      rates over 20%, even after clean procedures. The high rates of SSI are due in
      part to lack of infection control and surveillance policies in most hospitals in
      Africa. SSI is attended by complications, long hospital stay, and some mortality,
      but the economic consequences are unestimated. Typhoid fever and typhoid
      intestinal perforation are major problems with perforation rates of approximately
      10%, which is higher in older children. The ideal surgical treatment is arguable,
      but simple closure and segmental resection are the present effective surgical
      options. Because of delayed presentation, complications after surgical treatment
      are high with a mortality approaching 41% in some parts of Africa. Nutrition for
      these patients remains a challenge. Acute appendicitis, although not as common in
      African children, often presents rather late with up to 50% of children
      presenting with perforation and other complications, and mortality is
      approximately 4% is some settings. Pyomyositis and necrotizing fasciitis are the
      more common serious soft-tissue infections, but early recognition and prompt
      treatment should minimize the occasional mortality. Though common in Africa, the
      exact impact of human immunodeficiency virus infection on the spectrum and
      severity of surgical infection in African children is not clear, but it may well
      worsen the course of infection in these patients.

PMID- 22475118
TI  - Surgical implications of human immunodeficiency virus infections.
AB  - Pediatric HIV (human immunodeficiency virus) is a pandemic predominantly in sub
      Saharan Africa. Approximately 2.2 million children aged less than 15 years are
      infected with HIV, representing almost 95% of the total number of children
      globally infected with HIV. Therefore, increasing numbers of HIVi or -exposed but
      uninfected children can be expected to require a surgical procedure to assist in
      the diagnosis of an HIV/acquired immune deficiency syndrome-related complication,
      to address a life-threatening complication of the disease, or for routine surgery
      encountered in HIV-unexposed children. HIVi children may present with both
      conditions unique to HIV infection and surgical conditions routine in pediatric
      surgical practice. HIV exposure confers an increased risk of complications and
      mortality for all children after surgery, whether they are HIV infected or not.
      This risk of complications is higher in the HIVi group of patients. These
      findings seem to be independent of whether patients undergo an elective or
      emergency procedure, but the risk of an adverse outcome is higher for a major
      procedure. Surgical implications of HIV infection are comprehensively reviewed in
      this article.

PMID- 22475119
TI  - Challenge of pediatric oncology in Africa.
AB  - The care of children with malignant solid tumors in sub-Saharan Africa is
      compromised by resource deficiencies that range from inadequate healthcare
      budgets and a paucity of appropriately trained personnel, to scarce laboratory
      facilities and inconsistent drug supplies. Patients face difficulties accessing
      healthcare, affording investigational and treatment protocols, and attending
      follow-up. Children routinely present with advanced local and metastatic disease
      and many children cannot be offered any effective treatment. Additionally,
      multiple comorbidities, including malaria, tuberculosis, and HIV when added to
      acute on chronic malnutrition, compound treatment-related toxicities. Survival
      rates are poor. Pediatric surgical oncology is not yet regarded as a health care
      priority by governments struggling to achieve their millennium goals. The
      patterns of childhood solid malignant tumors in Africa are discussed, and the
      difficulties encountered in their management are highlighted. Three pediatric
      surgeons from different regions of Africa reflect on their experiences and review
      the available literature. The overall incidence of pediatric solid malignant
      tumor is difficult to estimate in Africa because of lack of vital hospital
      statistics and national cancer registries in most of countries. The reported
      incidences vary between 5% and 15.5% of all malignant tumors. Throughout the
      continent, patterns of malignant disease vary with an obvious increase in the
      prevalence of Burkitt lymphoma (BL) and Kaposi sarcoma in response-increased
      prevalence of HIV disease. In northern Africa, the most common malignant tumor is
      leukemia, followed by brain tumors and nephroblastoma or neuroblastoma. In sub
      Saharan countries, BL is the commonest tumor followed by nephroblastoma, non
      Hodgkin lymphoma, and rhabdomyosarcoma. The overall 5-years survival varied
      between 5% (in Cote d'Ivoire before 2001) to 34% in Egypt and up to 70% in South
      Africa. In many reports, the survival rate of patients is not mentioned but is
      clearly very low in many sub-Saharan Africa countries (Sudan, Nigeria). Late
      presentation was observed for many tumors like nephroblastoma in Nigeria, 72%
      were stages III and IV or BL stages III and IV were observed in 40% and 30%,
      respectively. Africa bears a great burden of childhood cancer. Cancer is now
      curable in developed countries as survival rates approach 80%, but in Africa,
      >80% of children still die without access to adequate treatment. Sharpening the
      needlepoint of surgical expertise will, of itself, not compensate for the major
      infrastructural deficiencies, but must proceed in tandem with resource
      development and allow heath planners to realize that pediatric surgical oncology
      is a cost-effective service that can uplift regional services.

PMID- 22475120
TI  - Parasitic infestations requiring surgical interventions.
AB  - Parasitic infestation is common in developing countries especially in Africa.
      Children are often more vulnerable to these infections. Many health problems
      result from these infestations, including malnutrition, iron-deficiency anemia,
      surgical morbidities, and even impaired cognitive function and educational
      achievement. Surgical intervention may be needed to treat serious complications
      caused by some of these parasites. Amoebic colitis and liver abscess caused by
      protozoan infections; intestinal obstruction, biliary infestation with
      cholangitis and liver abscess, and pancreatitis caused by Ascaris lumbricoides;
      biliary obstruction caused by Faschiola; hepatic and pulmonary hydatid cysts
      caused by Echinococcus granulosus and multilocularis are examples. Expenditure of
      medical care of affected children may cause a great burden on many African
      governments, which are already suffering from economic instability. The clinical
      presentation, investigation, and management of some parasitic infestations of
      surgical relevance in African children are discussed in this article.

PMID- 22475121
TI  - Neonatal surgery in Africa.
AB  - The management of neonatal surgical problems continues to pose considerable
      challenges, particularly in low-resource settings. The burden of neonatal
      surgical diseases in Africa is not well documented. The characteristics of some
      neonatal surgical problems are highlighted. Late presentation coupled with poor
      understanding of the milieu interior of the neonates by incompetent health care
      providers and poorly equipped hospitals combine to give rise to the unacceptable
      high morbidity and mortality in most parts of Africa. Proper training of all
      staff involved in neonatal health care coupled with community awareness must be
      vigorously pursued by all stakeholders. Various governments throughout the
      continent of Africa, in conjunction with international donor agencies, must not
      only provide an adequate budget for health care services and improve
      infrastructures, but must also deliberately encourage and provide funding for
      neonatal surgical care and research across the continent. The well-established
      pediatric surgical training programs, particularly in North and South Africa,
      should hold the moral responsibility of training all possible numbers of young
      surgeons from other African countries that do not have any existing pediatric
      surgical training programs or those countries suffering from remarkable shortage
      of trained pediatric surgeons.

PMID- 22475122
TI  - Pediatric minimally invasive surgery in Africa: limitations and current
      situation.
AB  - The second largest and most populous continent, with an exploding pediatric
      population, Africa has an overwhelming burden on its very limited pediatric
      surgical services. In an international environment of progressively advancing
      endoscopic and robotic surgical techniques, the authors focus on the current role
      of endoscopic surgery on the continent and explore the potential reasons for its
      delayed acceptance and implementation. They proceed to document the spectrum of
      what is available and, using their "African experience," expand on financially
      viable models of further rolling out these techniques, including discussion
      around suitable training models for surgeons and their teams.

PMID- 22475123
TI  - Liver transplantation in an African setting.
AB  - Liver disease in children in the developing world is a frequent occurrence, which
      is generally inadequately managed because of lack of resources. However,
      increasingly, there has been a demand for liver transplantation, where primary
      medical or surgical therapies have failed. The expertise and infrastructure
      required for a successful outcome are no different from those in more developed
      countries; if anything, the challenges are greater. Lack of deceased donors
      because of cultural and religious factors has driven the use of living donors.
      Short-term survival has generally been good, but long-term outcomes have rarely
      been reported. In this article, we review the experience of 2 centers at opposite
      ends of the continent and share our experience of slightly different settings and
      show that success can be achieved even in resource-reduced environments.

PMID- 22475124
TI  - Religiosity and tobacco and alcohol use in a Brazilian shantytown.
AB  - This article analyzes the role of religious involvement and religious beliefs in
      the prevalence and frequency of smoking and alcohol consumption. This was a cross
      sectional, population-based study. In 2005, we conducted door-to-door interviews
      with 383 people, aged 18 years or more, randomly selected from the "Paraisopolis"
      shantytown in Sao Paulo, Brazil. Four regression models were created to explain
      the relationships among religious involvement, tobacco and alcohol use,
      controlling for demographic, social, and psychobehavioral factors. High religious
      attendance was associated with less alcohol use, alcohol abuse, tobacco use, and
      combined alcohol/tobacco use, as well as less days consuming alcoholic beverages
      per week, controlling for confounding factors. Additionally, high
      nonorganizational religious behavior was associated with less tobacco and
      combined alcohol/tobacco use. Religiosity plays an important role in the control
      of alcohol and tobacco use in a shantytown setting; further management
      initiatives in the area should consider this issue. The study's limitations are
      noted.

PMID- 22475125
TI  - A normalization strategy for comparing tag count data.
AB  - BACKGROUND: High-throughput sequencing, such as ribonucleic acid sequencing (RNA
      seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, enables
      various features of organisms to be compared through tag counts. Recent studies
      have demonstrated that the normalization step for RNA-seq data is critical for a
      more accurate subsequent analysis of differential gene expression. Development of
      a more robust normalization method is desirable for identifying the true
      difference in tag count data. RESULTS: We describe a strategy for normalizing tag
      count data, focusing on RNA-seq. The key concept is to remove data assigned as
      potential differentially expressed genes (DEGs) before calculating the
      normalization factor. Several R packages for identifying DEGs are currently
      available, and each package uses its own normalization method and gene ranking
      algorithm. We compared a total of eight package combinations: four R packages
      (edgeR, DESeq, baySeq, and NBPSeq) with their default normalization settings and
      with our normalization strategy. Many synthetic datasets under various scenarios
      were evaluated on the basis of the area under the curve (AUC) as a measure for
      both sensitivity and specificity. We found that packages using our strategy in
      the data normalization step overall performed well. This result was also observed
      for a real experimental dataset. CONCLUSION: Our results showed that the
      elimination of potential DEGs is essential for more accurate normalization of RNA
      seq data. The concept of this normalization strategy can widely be applied to
      other types of tag count data and to microarray data.

PMID- 22475126
TI  - Perinatal health in rural Burkina Faso.

PMID- 22475127
TI  - Crystal structure of a membrane stomatin-specific protease in complex with a
      substrate peptide.
AB  - Membrane-bound proteases are involved in various regulatory functions. A previous
      report indicated that the N-terminal region of PH1510p (1510-N) from the
      hyperthermophilic archaeon Pyrococcus horikoshii is a serine protease with a
      catalytic Ser-Lys dyad (Ser97 and Lys138) and specifically cleaves the C-terminal
      hydrophobic region of the p-stomatin PH1511p. In humans, an absence of stomatin
      is associated with a form of hemolytic anemia known as hereditary stomatocytosis.
      Here, the crystal structure of 1510-N K138A in complex with a peptide substrate
      was determined at 2.25 A resolution. In the structure, a 1510-N dimer binds to
      one peptide. The six central residues (VIVLML) of the peptide are hydrophobic and
      in a pseudopalindromic structure and therefore favorably fit into the hydrophobic
      active tunnel of the 1510-N dimer, although 1510-N degrades the substrate at only
      one point. A comparison with unliganded 1510-N K138A revealed that the binding of
      the substrate causes a large rotational and translational displacement between
      protomers and produces a tunnel suitable for binding the peptide. When the
      peptide binds, the flexible L2 loop of one protomer forms beta-strands, whereas
      that of the other protomer remains in a loop form, indicating that one protomer
      binds to the peptide more tightly than the other protomer. The Ala138 residues of
      the two protomers are located very close together (the distance between the two
      Cbeta atoms is 3.6 A). Thus, in wild-type 1510-N, the close positioning of the
      catalytic Ser97 and Lys138 residues may be induced by electrostatic repulsion of
      the two Lys138 side chains of the protomers.

PMID- 22475128
TI  - Depressive symptoms are associated with weight gain among women.
AB  - BACKGROUND: Many studies have linked depression and obesity; few have more than
      two assessments of depressive symptoms and adiposity to address the potential
      bidirectional relationship between adiposity and depressive symptoms from young
      adulthood through old age. We tested whether baseline depressive symptoms are
      associated with changes in weight, whether baseline adiposity is associated with
      changes in depressive symptoms, and whether these associations vary by sex.
      METHOD: Participants (n=2251; 47% female) were from the Baltimore Longitudinal
      Study of Aging (BLSA). Using hierarchical linear modeling (HLM) on 30 years of
      data, the trajectory of adiposity and depressive symptoms over adulthood was
      estimated from >10 000 observations (mean=4.5 assessments per participant) of
      body mass index (BMI; kg/m2), waist circumference and hip circumference and >10
      000 observations (mean=4.5 assessments per participant) of the Center for
      Epidemiological Studies Depression Scale (CES-D). Baseline depressive symptoms
      and adiposity were then tested as predictors of the trajectory of adiposity and
      depressive symptoms respectively. Additional analyses tested for sex-specific
      associations. RESULTS: Sex moderated the association between depressive symptoms
      and weight gain such that women who experienced depressed affect had greater
      increases in BMI (b(interaction)=0.12, S.E.=0.04), waist (b(interaction)=0.22,
      S.E.=0.10) and hip circumference (b(interaction)=0.20, S.E.=0.07) across the
      adult lifespan, controlling for relevant demographic and behavioral covariates.
      Baseline adiposity was unrelated to the trajectory of depressive symptoms (median
      b=0.00) for both sexes. CONCLUSIONS: Women who experience symptoms of depression
      tend to gain more weight across adulthood than men who experience such symptoms.
      Whether an individual was normal weight or overweight was unrelated to changes in
      depressive symptoms across adulthood.

PMID- 22475129
TI  - Nucleophosmin gene-based monitoring in de novo cytogenetically normal acute
      myeloid leukemia with nucleophosmin gene mutations: comparison with
      cytofluorimetric analysis and study of Wilms tumor gene 1 expression.
AB  - We compared the clinical value of minimal residual disease (MRD) monitoring by
      cytofluorimetric methods, Wilms tumor gene 1 (WT1) expression and the study of
      nucleophosmin gene (NPM) mutations in a series of 26 patients with NPM-mutated de
      novo acute myeloid leukemia (NPM-AML) who achieved complete hematological
      remission after conventional chemotherapy. The relapse risk was significantly
      lower only in patients achieving a NPM molecular complete response (NPM mol-CR)
      and confirmed NPM mol-CR (non-detectable NPM mutations in two consecutive marrow
      samples). The disease-free survival (DFS) of patients achieving a < 4-log or >= 4
      log reduction in NPM value after induction therapy was 12.6 % and 50%,
      respectively, at 36 months (p = 0.009). The attainment of a confirmed NPM-CR had
      a significant influence on overall survival (OS at 36 months was 64.3% and 11.9%
      in patients obtaining or not obtaining confirmed NPM-CR, respectively, p < 0.03).
      We confirm that NPM-molecular relapse (NPM-rel) is always followed by
      hematological relapse (H-rel), but longitudinal studies of NPM mutations may
      predict an impending H-rel earlier than flow cytometric- or WT1-based methods.

PMID- 22475130
TI  - Age-related differences in the reproductive and metabolic implications of
      polycystic ovarian syndrome: findings in an obese, United States population.
AB  - The objective of this study was to explore age-related differences in the
      reproductive and metabolic manifestations of polycystic ovarian syndrome (PCOS).
      Using a prospective cross-sectional design, we compared metabolic and
      reproductive findings in women attending a multidisciplinary clinic for PCOS,
      stratified across the following age groups: 18-25 (n = 71), 26-35 (n = 129), and
      36-45 (n = 29). The study included primarily overweight and obese women, with a
      mean BMI of 31.1 in the entire study group. Older women had a decreased
      prevalence of biochemical hyperandrogenemia (p-trend: 0.0005). Of women meeting
      diagnostic criteria for PCOS, older women (n = 15) had larger median waist
      circumference and higher median diastolic blood pressure, total cholesterol, LDL
      cholesterol and fasting glucose compared to younger women (p-trend: 0.03, 0.01,
      0.01, 0.01 and 0.06, respectively). The odds of metabolic syndrome for women ages
      36-45 are increased four-fold relative to the younger groups (OR: 4.01; 95% CI:
      1.04-15.4; p = 0.04). We conclude that there are significant age-related
      differences in both the clinical presentation and metabolic manifestations of
      PCOS.

PMID- 22475131
TI  - Two-dimensional short-range disordered crystalline networks from flexible
      molecular modules.
AB  - Studies of complex condensed matter systems have led to the discovery of
      materials of unexpected spatial organization as glasses, glassy crystals,
      quasicrystals, and protein and virus crystals. Here, we present two-dimensional
      (2D) short-range disordered molecular crystalline networks, which, regarding
      spatial organization, can be considered as surface analogues of 3D glassy
      crystals. In particular, the deposition of a flexible molecular module on Cu(111)
      gives rise to distinct phases whose characteristics have been examined in real
      space by scanning tunneling microscopy: a 2D short-range distortional disordered
      crystalline network and a 2D short-range orientational disordered crystalline
      network, respectively. Both phases exhibit a random arrangement of nanopores that
      are stabilized by the simultaneous presence of metal-organic and pyridyl-pyridyl
      interactions. The 2D short-range distortional disordered crystalline network
      displayed intriguing flexibility, as probed by the STM tip that modifies the pore
      shape, a prerequisite for adaptive behavior in host-guest processes.

PMID- 22475132
TI  - Spanish version of the Geriatric Depression Scale: reliability and validity in
      persons with mild-moderate dementia.
AB  - BACKGROUND: Depressive symptoms are prevalent among persons with dementia (PWD).
      Our aim was to assess the psychometric properties of the Spanish version of the
      Geriatric Depression Scale (GDS-15 and GDS-5) in PWD. METHODS: In this cross
      sectional study, five healthcare centers providing care for PWD from two cities
      in Spain participated. Ninety-six community-dwelling PWD aged 55 years and older,
      living with a known caregiver, completed a battery of scales including the GDS-15
      and GDS-5, the Cornell Scale Depression in Dementia (CSDD), a list of self
      reported chronic health conditions (yes/no), severity of dementia (Mini-Mental
      State Examination), functional status (Barthel Index), generic quality of life
      (WHOQOL-BREF), and sociodemographic information. RESULTS: Cronbach's alpha
      coefficients were 0.81 and 0.72 for GDS-15 and GDS-5, respectively, providing
      evidence for acceptable internal consistency. Significant associations between
      the GDS-15/GDS-5, the Barthel Index, CSDD, and the WHOQOL-BREF were found. No
      significant differences were found on GDS-15/GDS-5 scores among dementia
      diagnostic groups (Alzheimer's disease, vascular dementia, mixed dementia, other
      dementia) or between mild (MMSE 21-26) and moderate (MMSE 10-20) dementia.
      Participants self-reporting depression on the comorbid condition list (yes)
      scored significantly higher on the GDS-15 and GDS-5 compared to those who
      reported not having depression. Exploratory factor analyses suggested a two
      factor structure on GDS-15 which accounted for 41.6% of the variability, while
      the one-factor structure on the GDS-5 accounted for 48.1% of the variability.
      CONCLUSIONS: In general, this study provides evidence that GDS-15 and GDS-5 are
      suitable measures for screening depressive symptoms in community-dwelling PWD.

PMID- 22475133
TI  - Switchable wettability sensor for ion pairs based on calix[4]azacrown clicking.
AB  - A new calix[4]azacrown is synthesized from 1,3-dipropynyloxycalix[4]arene in a
      good yield of 85% and was modified on a silicon surface via click chemistry to be
      a switchable wettability sensor for ion pairs ([C(4)mim]Cl). A cooperative
      mechanism involving supramolecular interactions is proposed.

PMID- 22475134
TI  - Derivation of coarse grained models for multiscale simulation of liquid
      crystalline phase transitions.
AB  - We present a systematic derivation of a coarse grained (CG) model for molecular
      dynamics (MD) simulations of a liquid crystalline (LC) compound containing an
      azobenzene mesogen. The model aims at a later use in a multiscale modeling
      approach to study liquid crystalline phase transitions that are (photo)induced by
      the trans/cis photoisomerization of the mesogen. One of the major challenges in
      the coarse graining process is the development of models that are for a given
      chemical system structurally consistent with for example an all-atom reference
      model and reproduce relevant thermodynamic properties such as the LC phase
      behavior around the state point of interest. The reduction of number of degrees
      of freedom makes the resulting coarse models by construction state point
      dependent; that is, they cannot easily be transferred to a range of temperatures,
      densities, system compositions, etc. These are significant challenges, in
      particular if one wants to study LC phase transitions (thermally or
      photoinduced). In the present paper we show how one can systematically derive a
      CG model for a LC molecule that is highly consistent with an atomistic
      description by choosing an appropriate state point for the reference simulation.
      The reference state point is the supercooled liquid just below the smectic
      isotropic phase transition which is characterized by a high degree of local
      nematic order while being overall isotropic. With the resulting CG model it is
      possible to switch between the atomistic and the CG levels (and vice versa) in a
      seamless manner maintaining values of all the relevant order parameters which
      describe the smectic A (smA) state. This model will allow us in the future to
      link large length scale and long time scale CG simulations of the LC state with
      chemically accurate QM/MM simulations of the photoisomerization process.

PMID- 22475135
TI  - Hepatitis B virus infections and risk factors among the general population in
      Anhui Province, China: an epidemiological study.
AB  - BACKGROUND: Hepatitis B is one of the most common infectious diseases in China.
      The aim of this study was to determine the prevalence of hepatitis B surface
      antigen (HBsAg) among the general population and the risk factors associated with
      HBV infection in Anhui province, China. METHODS: A provincial serosurvey was
      conducted in four cities, and selected through stratified clustering sampling.
      Data on demographics, immunization history, medical history, family medical
      history, and life history were collected, along with serum tested for HBsAg.
      Completed surveys were analysed from 8,875 participants. RESULTS: Overall
      prevalence of HBsAg was 7.44%. Using multivariate analysis, older age was a risk
      factor for HBsAg infection among children younger than 15 years. Among adults 15
      59 years old, the risk factors were male gender, a history of surgical
      operations, at least one HBsAg-positive family member, and non-vaccination. For
      adults older than 59 years, the risk factor was a blood transfusion history.
      CONCLUSIONS: Though Anhui province has already reached the national goal of
      reducing HBsAg prevalence to less than 1% among children younger than 5 years,
      there are still several risk factors for HBsAg infection among the older
      population. Immunization programs should continue to focus on adults, and
      interventions should be taken to reduce risk factors associated with being
      infected with Hepatitis B.

PMID- 22475136
TI  - [Clinical and pathological features in 138 cases of drug-induced liver injury].
AB  - OBJECTIVE: To explore the categories of drugs causing hepatotoxicity and analyze
      the clinical and histological features of the corresponding drug-induced liver
      injury (DILI), in order to gain insights into potential diagnostic factors for
      DILI. METHODS: A total of 138 DILI patients treated at our hospital from April
      2008 to April 2010 were retrospectively analyzed. The responsible drug for each
      DILI case was recorded. The Roussel Uclaf Causality Assessment Method (RUCAM) had
      been used to diagnose DILI. Only cases that had scored as highly probable or
      probable (more than or equal to 6 points by RUCAM) were included in this study.
      The patients' general condition, clinical manifestations, and serum biochemical
      and immunological parameters were assessed. Sixty-six of the patients underwent
      liver biopsy, and were assessed for liver pathological changes. Clinical and
      laboratory test data were collected and used to classify the total 138 cases as
      hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types.
      RESULTS: Within our patient population, the leading cause of DILI was Chinese
      herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in
      7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the
      clinical features and histological injury pattern was stronger at the time of
      biopsy (more than or equal to 3 days after laboratory results) (kappa = 0.63, P
      less than 0.05) than at the onset of DILI (kappa = 0.25, P less than 0.05). All
      modified hepatic activity index (HAI) necroinflammatory scores and fibrosis
      scores were more severe in the cholestatic and mixed injury types than in the
      hepatocellular injury type (P less than 0.01 and P less than 0.05, respectively).
      CONCLUSION: Chinese herbal medicine, dietary supplements and antibiotics were the
      main causes of DILI in our patient population. The clinical and histological
      features correlated well, especially at later stages of DILI. The degree of
      inflammation and fibrosis was significantly higher in cholestatic and mixed
      hepatocellular-cholestatic injury types than in the hepatocellular injury type.
      Assessment of both clinical and pathological features may represent a more
      accurate diagnostic method for DILI.

PMID- 22475137
TI  - [Set up drug lymphocyte stimulation test (3H-TdR) and observe its application in
      drug-induced liver injury].
AB  - OBJECTIVE: To set up the drug lymphocyte stimulation test (DLST), as a diagnosis
      means for DILI which was immunity idiosyncrasy, improve the Diagnosis, level of
      DILI. METHOD: For the 59 patients who diagnosed as DILI, we separated their PBMC,
      exploring to the suspicious drug which caused DILI, then use the methods 3H-TdR
      to test, according to the mixed degree to clear the PBMC count which specific
      activated by drug.We also set up drug group, negative control and Positive
      control at the same time. Preliminary experiments was including the best dose of
      PHA and the best concentration of the drug. We set up 40 healthy group in our
      experiments as a control, and explore them on the same drug every time. We test
      the two groups at the same time. We handled the results use t-test. RESULTS: The
      methods 3H-TdR could be exactly reflect the PBMC's proliferation degree nearly
      the same when they were be stimulation by PHA or the sensitive drug. When the
      DILI patients were explore to the suspicious drug, their stimulation index (SI)
      Obviously higher than 1.8. Form this test, there were 28 in 59 patients of DILI's
      group were positive (47.46%), SI was from 1.9 to 43.08, the average was 22.49,
      the healthy group SI was lower than 1.8, the SI of DILI's group was significantly
      higher than healthy group (5.78+/-0.75/1.16+/-0.25, P less than 0.05). Our test
      suggested DLST has Higher specificity (94.92%) and sensitivity (47.46%).
      CONCLUSION: DLST was significance for the patients who diagnosed as immunity
      idiosyncrasy's DILI, it's reflected these patients' Proliferation of PBMC when
      explored to the suspicious drug for the second time.

PMID- 22475138
TI  - [Clinical characteristics of drug-induced liver injury in 31 pediatric cases].
AB  - OBJECTIVE: To investigate the clinical characteristics and responsible agents of
      drug-induced liver injury (DILI) in pediatric patients. METHODS: Thirty-one cases
      of DILI treated in our hospital's pediatric ward were retrospectively analyzed.
      The clinical data for each patient were extracted from the patient's medical
      records, and included reported causes, physical and biochemical features, natural
      history, blood examination results, and hepatic pathology findings. RESULTS: The
      31 pediatric cases of DILI accounted for 1.7% of the 1831 total cases of drug
      induced liver injury treated at our hospital between February 2002 to June 2011.
      The pediatric DILI population was composed of 20 males and 11 females, with an
      average age of 8.8+/-3.9 years old (range, 0.3-14.0). The liver injury patterns
      represented among the cases were: hepatocellular (25.8%), cholestasis (25.8%),
      and mixed hepatocellular-cholestatic (48.4%). Antimicrobials were the most common
      cause (41.9%) of DILI, followed by the herbal medicine (29.0%) and febrifuge
      drugs (19.4%). A single drug was implicated in nine cases (29.0%), and two or
      more drugs were implicated in 22 cases (71%). Most of the children had good
      prognosis, but those with pre-existing disease had poor prognosis. One child died
      of hepatic failure, making the death rate 3.23%. The average hospitalization time
      was 25.2 days, and the patients with hepatocellular injury had shorter
      hospitalization time than those with mixed injury. CONCLUSION: Drug-induced liver
      injury in our pediatric population was most often caused by antimicrobials,
      followed by herbal medicine and febrifuge drugs. Most patients presented with
      mixed hepatocellular-cholestatic injury. Children with pre-existing diseases or
      hepatic failure had poor prognosis.

PMID- 22475139
TI  - [Expression and significance of insulin-like growth factor-1 and insulin-like
      growth factor binding protein-3 in hepatocyte steatosis model].
AB  - OBJECTIVE: To investigate the expression of IGF-1 and IGFBP-3 in nonalcoholic
      fatty steatosis hepatocyte models induced by oleic acid. METHOD: Nonalcoholic
      fatty steatosis hepatocyte models induced by oleic acid on immortalized human
      hepatocyte, Oil red O staining and intracellular triglycerides were detected for
      observing the situation of IHH cells fatty degeneration. IHH cells were divided
      into control group, NAFLD group, which the control group cultured in DMEM/F12
      medium, NAFLD group were treated with oleic acid, 0.5 mmol/L treatment for 72 h.
      The expression of mRNA and protein of IGF-1 and IGFBP3 were measured by
      immunofluorescent staining, Western blot and RT-PCR methods. Between the two
      groups were compared using the t- test. RESULTS: The steatosis models of the
      hepatocytes were established successfully with 0.5 mmol/L oleic acid. Lipid
      droplets were observed through Oil red O staining. The level of hepatocyte TG was
      increased (275.7+/-27.2) mug/mg from (150.2+/-15.6) mug/mg (t = 21.67, P less
      than 0.01). Compared with the control group, the mRNA of IGF-1 (0.76+/-0.04 vs
      4.82+/-1.51, t = 17.915, P less than 0.01), IGFBP-3 (1.58+/-0.93 vs 5.41+/-1.37,
      t = 12.893, P less than 0.01) and protein expression of IGF-1 (1.00+/-0.29 vs
      2.56+/-0.71, t = 29.17, P less than 0.01), IGFBP-3 (0.65+/-0.36 vs 1.23+/-0.91, t
      = 32. 12, P less than 0.01) significantly decreased in oleic acid-treated group.
      The results of immunofluorescence staining also confirm the significantly
      decreased protein expression of IGF-1 and IGFBP-3 in NAFLD group compared with
      control group. CONCLUSION: The expression of IGF-1 and IGFBP-3 decreased in
      nonalcoholic fatty steatosis hepatocyte models, which will provide the
      experimental basis for the further study of the mechanism of the limited height
      of some children with non-alcoholic fatty liver disease in clinical.

PMID- 22475140
TI  - [Efficacy and safety of telbivudine in pregnant women to prevent perinatal
      transmission of hepatitis B virus].
AB  - OBJECTIVE: To evaluate the efficacy and safety of telbivudine use during the
      second and third trimester of pregnancy for reducing hepatitis B virus (HBV)
      transmission from highly viremic hepatitis B e antigen-positive (HBeAg+) mothers
      to their fetuses. METHODS: Pregnant women, between weeks 20 to 32 of gestation,
      who were HBeAg+ and had HBV DNA more than 1.0*10(7) copies/mL were enrolled in
      our study. The women were offered inclusion into one of two treatment arms, based
      upon their personal preference: telbivudine or no telbivudine. The patients in
      the telbivudine treatment arm were administered 600 mg/d telbivudine at least
      until postpartum week 4. All delivered infants in both treatment arms were
      administered hepatitis B immune globulin (HBIG; 200 IU) within 12 hours of
      delivery and recombinant HBV vaccine (20 mug) at 0, 1 and 6 months. The HBV
      perinatal transmission rate was determined by measuring HBsAg and HBV DNA in
      infants at postpartum week 28. RESULTS: A total of 220 pregnant women were
      enrolled in our study, 120 chose the telbivudine arm and 100 chose the control
      arm. All telbivudine treated subjects were registered in the Antiretroviral
      Pregnancy Registry. Telbivudine treatment was associated with a marked reduction
      in the mothers' serum HBV DNA, HBeAg and ALT levels before delivery. A striking
      decline of HBV DNA levels in treated mothers was observed at week 2 of treatment,
      which was followed by a gradual and steady decrease that continued until
      delivery. Thirty-seven (31%) of the telbivudine-treated mothers and none (0%) of
      the untreated controls had polymerase chain reaction-undetectable viremia at
      delivery. At week 28, 0% of the infants delivered from telbivudine-treated
      mothers were HBsAg+ or HBV DNA+, as compared to 8% HBsAg+ or HBV DNA+ in the
      untreated control arm (P = 0.002). No telbivudine discontinuations occurred from
      adverse events, and no congenital deformities were observed in the infants
      delivered to telbivudine-treated mothers. Eighty mothers discontinued telbivudine
      at week 4 postpartum, and there were no cases of severe hepatitis. There were no
      significant differences between the two treatment arms for postpartum hemorrhage,
      adverse events during pregnancy, cesarean section, gestational age, or infants'
      height/weight or Apgar scores. CONCLUSIONS: Telbivudine use during the second and
      third trimester of pregnancy in HBeAg+ highly viremic mothers can safely reduce
      perinatal HBV transmission rates. Telbivudine was well-tolerated by our patient
      group. Furthermore, no safety concerns were observed in either the telbivudine
      treated mothers or their delivered infants in short term follow-up.

PMID- 22475141
TI  - [Changing characteristic of blood coagulation factors and their correlation with
      blood coagulation status in different hepatic diseases].
AB  - OBJECTIVE: To investigate the correlation between pro coagulation factors and
      anti-coagulation factors synthesized by the liver, and the correlation between
      fibrin degradation products (FDP) and D-dimer (D-D) concentration and coagulation
      proteins synthesized by extra-hepatic tissues, in different liver diseases; to
      explore the relationship between coagulation and bleeding in hepatic diseases.
      METHODS: Chronic hepatitis B (CHB) patients, CHB-related liver cirrhosis
      patients, CHB-related liver failure patients and healthy (normal) controls were
      selected for study and provided blood samples for analysis. The activity of
      coagulation factors (F) II, V, VII, VIII, IX, X, XI, and XII was detected using
      the one-stage clotting method. Coagulogram analysis, including activated partial
      thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT), was
      conducted by the solidification method. Antithrombin III (AT-III) and protein C
      (PC) activities were measured by chromogenic substrate assay. FDP concentration
      was detected using immunoturbidimetry. Tissue factor pathway inhibitor (TFPI),
      thrombomodulin (TM), von Willebrand factor (vWF), and tissue factor (TF)
      concentrations were measured by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: With the exception of FVIII, coagulation factors and anticoagulant
      proteins synthesized by the liver were decreased and the coagulogram was extended
      for all patients. Likewise, the FDP and D-D concentrations were increased in
      blood. CHB patients, however, presented with increased levels of FVIII, TFPI, TM,
      vWF, and TF. Pairwise comparison indicated statistical differences existed among
      CHB, CHB-related liver cirrhosis, and liver failure patients: TFPI: 239.3+/
      206.4, 315.0+/-258.6, and 319.5+/-298.1 -- higher than normal control: 104.0+/
      87.1, F = 5.453, P less than 0.05; vWF: 70.3+/-29.5, 105.5+/-58.0, and 179.3+/
      61.7 -- higher than normal control: 21.9+/-7.2, F = 20.104, P less than 0.05; TF:
      85.9+/-85.7, 234.2+/-202.9, and 344.7+/-214.6 -- higher than normal control:
      12.8+/-8.1, F = 8.619, P less than 0.05; FVIII: 157.2+/-53.4, 206.9+/-86.9, and
      335.7+/-117.7 -- higher than normal control: 105.5+/-46.2, F = 13.418, P less
      than 0.05. CONCLUSION: In parallel to the progression of liver diseases, pro
      coagulation and anti-coagulation elements synthesized by the liver were reduced.
      In contrast, fibrinolysis activity was enhanced, which is expected to lead to an
      imbalance between blood clotting and anti-clotting factors. This may be an
      important cause for the bleeding that occurs in end-stage liver disease.
      Expressions of TFPI, TM, vWF, and TF significantly change in the early stage of
      liver diseases, as compared to normal (healthy) levels, and may represent a
      sensitive indicator of vascular injury.

PMID- 22475142
TI  - [Effect of hepatitis B virus X protein on the cell cycle of primary mouse
      hepatocytes].
AB  - OBJECTIVE: To investigate the effect of hepatitis B virus (HBV) X protein (HBx)
      on host cell cycle and HBV replication using cultured primary mouse hepatocytes
      to gain further insights into the mechanism of HBx-mediated modulation of cell
      cycle. METHODS: Primary cultured mouse hepatocytes were transfected with HBx
      expressing (pHBV) or HBx-selected (pHBV triangle X) plasmids, which were
      generated with sequences of the HBV ayw subtype 1.2 and included the green
      fluorescent protein (GFP) reporter gene. The levels of cell cycle proteins (p16,
      cyclin D1, p21, cyclin E and cyclin A) were measured with Western blotting, and
      HBV DNA was analyzed by Southern blotting and real-time PCR. RESULTS: The freshly
      isolated hepatocytes showed no significant differences in levels of cell cycle
      proteins. However, at 48 hours post-transfection, the levels of cyclin D1, p21
      and cyclin E were significantly higher and the level of p16 was significantly
      lower in the pHBV-transfected hepatocytes than in the pHBV triangle X-transfected
      hepatocytes (t = 15.713, 22.897, 14.680, and -19.584, respectively, P less than
      0.05). The level of cyclin A was not different between the two groups (t = 0.142,
      P more than 0.05). At 72 hours post-transfection, the level of HBV DNA was higher
      in pHBV-transfected hepatocytes (rcDNA: 3288.336+/-448.011; dslDNA: 6458.318+/
      182.163; ssDNA: 2760.613+/-393.561) than in pHBV triangle X-transfected
      hepatocytes (rcDNA: 515.721+/-62.530; dslDNA: 2122.228+/-28.347; ssDNA:
      1632.013+/-207.021) and in the blank (untransfected) control group (P less than
      0.05). Real-time PCR analysis of HBV DNA copy number per cell confirmed these
      results, (pHBV-transfected: 987.50+/-47.80 vs. pHBV triangle X-transfected:
      303.67+/-33.94; t = 20.203, P less than 0.05). CONCLUSIONS: The HBx protein can
      affect the levels of cell cycle proteins, which may induce quiescent hepatocytes
      to enter the G1 phase of the cell cycle and stay in this phase instead of
      entering the S phase, thereby promoting HBV intracellular replication.

PMID- 22475143
TI  - [Analysis of thyroid dysfunction and influencing factors in chronic hepatitis C
      patients treated with peg-IFNa-2a and ribavirin].
AB  - OBJECTIVE: To analyze the frequency of thyroid dysfunction and determine its
      influencing factors in chronic hepatitis C (CHC) patients treated with pegylated
      interferon alpha (peg-IFNa)-2a and ribavirin (RBV) combination therapy. METHODS:
      A total of 194 CHC patients were treated with peg-IFNa-2a and RBV for 48 weeks.
      Development of thyroid dysfunction was recorded. Clinical and biological factors
      from pre-treatment (baseline) to post-treatment were statistically analyzed to
      determine correlation with thyroid dysfunction in this patient population.
      RESULTS: Fifty-two (26.80%) of 194 peg-IFNa-2a/RBV-treated patients developed
      thyroid dysfunction. Dysfunction severity ranged from hyperthyroidism (n = 1,
      0.52%) and hypothyroidism (n = 10, 5.15%) to subclinical hyperthyroidism (n = 4,
      2.06%) and subclinical hypothyroidism (n = 37, 19.07%). The dysfunction rate was
      significantly higher after peg-IFNa-2a/RBV treatment (26.80% vs. 12.37% at
      baseline, x2 = 12.829, P less than 0.05, odds ratio (OR) = 0.386, 95% confidence
      interval (CI): 0.226-0.657), in females (33.00% vs. 20.21% in males, P less than
      0.05, 95% CI: 1.016-3.040), and in thyroid auto-antibody positive patients
      (64.29% vs. 23.89% in negative patients, P less than 0.05, 95% CI: 1.681-36.183).
      Early virological response did not have any significant effect on dysfunction
      rate (23.00% vs. 30.85% no early virological response, x2 = 1.522, P more than
      0.05) nor did end of treatment response (27.19% vs. 26.25% no response at end of
      treatment, x2 = 0.021, P more than 0.05). Patients who developed thyroid
      dysfunction had higher interleukin (IL)-6 at baseline (i.e. before peg-IFNa
      2a/RBV treatment) (27.08+/-14.90 vs. 11.65+/-5.46 in patients who maintained
      normal thyroid function, t = 3.127, P less than 0.05, 95% CI: 5.28-25.58). IL-6
      levels were not significantly different between the two groups at 24 weeks
      (6.30+/-2.47 vs. 6.81+/-2.80, t = 0.352, P more than 0.05). IL-6 levels before
      and after 48 weeks of treatment in normal thyroid function patients were 27.08+/
      14.90 and 6.30+/-2.47, t = 3.632, P less than 0.05, and in thyroid dysfunction
      patients were 11.65+/-5.46 and 6.81+/-2.80, t = 1.997, P more than 0.05.
      CONCLUSION: Peg-IFNa-2a/RBV combination therapy may cause thyroid dysfunction,
      especially hypothyroidism, in CHC patients. Female sex and thyroid auto-antibody
      positivity may put CHC patients at higher risk of developing thyroid dysfunction
      during peg-IFNa-2a/RBV therapy. Elevated IL-6 may be a predictive marker of peg
      IFNa-2a/RBV-induced thyroid dysfunction.

PMID- 22475144
TI  - [Antioxidant effects of the Uygur herb, Foeniculum Vulgare Mill, in a rat model
      of hepatic fibrosis].
AB  - OBJECTIVE: To evaluate therapeutic and antioxidant effects of Uygur Herb
      Foeniculum Vulgare Mill (FVM) in hepatic fibrosis rats. METHOD: Hepatic fibrosis
      model was built in rats by subcutaneous injection with 40% CCl4 olive oil
      mixture. At the same time the rats were given high lipoid-low protein animal
      feeds for 5 weeks. 94 male SD rats were randomly divided into six groups :blank
      control group (A-group), 8 rats were feed in normal; prevention model control
      group (B-group), 10 rats were given saline solution by intragastric
      administration during make of hepatic fibrosis model; FVM prevention group (C
      group), 10 rats were given FVM by intragastric administration during make of
      hepatic fibrosis model; model control group (D-group), FVM treatment group (E
      group); Fuzhenghuayu treatment group (F-group). 22 rats in each D, E, F-group
      were respectively given saline solution, FVM and Fuzhenghuayu by intragastric
      administration after hepatic fibrosis model were built. At the 5-th weekend, A,
      B, C- group rats were sacrificed. At the 6-th, 7-th, 8-th, 9-th weekend, 4-6 rats
      in D, E, F-group were sacrificed. Serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), hyaluronic acid (HA), laminin (LN) and 8 - hydroxy-2
      deoxyguanosine (8-OHdG) were detected, liver tissue homogenate superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) were
      detected. Histopathologic changes were observed after H.E and Masson staining.
      The expression of alpha-smooth muscle actin(a-SMA) were detected by
      immunohistochemical staining. The data were analyzed by SPSS17.0 software.
      RESULTS: The serum levels of ALT, AST, HA, and LN in the FVM prevention group
      were significantly reduced compared to the prevention model control group.(P less
      than 0.05). Rats in FVM treatment group appeared a marked lower serum levels of
      ALT, AST, HA compared to the model control group (P less than 0.05), and a
      distinguished lower Inflammation grade and fibrosis stage (P less than 0.05) when
      the liver section were assayed as well; Rats in FVM treatment group and FVM
      prevention group had a conspicuous lower content of MDA, 8-OHdG, fibre and a-SMA
      expression (P less than 0.05), a significantly higher level of SOD, GSH-Px
      compared to those of in the model control groups. CONCLUSIONS: Foeniculum Vulgare
      Mill declines liver inflammation response ,and prevent the hepatic fibrosis
      progression,, this may be due to its effects of antioxidative results.

PMID- 22475145
TI  - [The effects of p38MAPK and HBxAg on cell proliferation and apoptosis in human
      hepatocarcinogenesis].
AB  - OBJECTIVE: To investigate the effects of host-derived p38 mitogen-activated
      protein kinase subunit 38 (p38MAPK) and the hepatitis B virus X antigen (HbxAg)
      on cell proliferation and apoptosis in human hepatocellular carcinoma (HCC), and
      to study the mechanism underlying hepatocarcinogenesis. METHODS: Liver tissues
      were biopsied from healthy individuals and patients with chronic hepatitis B
      (CHB), liver cirrhosis, paratumor cirrhosis, and HCC. Immunohistochemical
      staining was used to detect expressions of HBxAg, p38MAPK, cell cycle G2/M phase
      related factors (cdc25B, p34cdc2, cyclin B1), and cell proliferation factor ki
      67.The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      method (known as TUNEL) was used to detect apoptosis. RESULTS: The highest rates
      of HBxAg were detected in CHB (65.0%) and HCC (44.4%) liver samples, and the
      antigen was mainly expressed in nuclei. Increasingly higher rates of p38MAPK,
      cdc25B, cyclin B1, and p34cdc2 expression were detected with increases in disease
      severity: normal liver (40.0%, 20.0%, 20.0%, and 30.0%, respectively), chronic
      hepatitis B (60.0%, 65.0%, 40.0%, and 50.0%, respectively), liver cirrhosis
      (65.0%, 75.0%, 70.0%, and 55.0%, respectively), paratumor cirrhosis (66.7%,
      75.0%, 75.0%, and 63.9%, respectively), and HCC (77.8%, 80.6%, 80.6%, and 72.2%,
      respectively). In addition, the intracellular location of p38MAPK expression was
      different under different disease conditions, showing nuclear expression in CHB
      and liver cirrhosis samples and cytoplasmic expression in paratumor cirrhosis and
      HCC samples (x2 = 1.11, P more than 0.05). The proliferation index (PI) and the
      apoptosis index (AI) were both increased along with disease severity (normal more
      than CHB more than paratumor cirrhosis more than HCC) (PI: 0.0000+/-0.000,
      0.0502+/-0.011, 0.0411+/-0.009, 0.0762+/-0.017; AI: 0.0351+/-0.024, 0.0607+/
      0.022, 0.0562+/-0.013, 0.0716+/-0.011), with the notable exception for liver
      cirrhosis (PI: 0.1810+/-0.036 and AI: 0.1200+/-0.018). PI in poorly
      differentiated HCC (0.2285+/-0.062) was significantly higher than in well
      differentiated HCC (0.1216+/-0.032, t = 2.082, P = 0.044). AI in well
      differentiated HCC (0.152+/-0.026) was significantly higher than in poorly
      differentiated HCC (0.081+/-0.022, t = 2.129, P = 0.041). CONCLUSIONS: In the
      process of hepatocarcinogenesis, HBxAg may cause a series of abnormal changes in
      cell cycle, proliferation and apoptosis by affecting the expression of p38MAPK.

PMID- 22475146
TI  - [Histone deacetylase inhibitor MS-275 treatment alters immune molecule content
      and categories in hepatocarcinoma exosomes].
AB  - OBJECTIVE: To investigate the effects of the histone deacetylase inhibitor, MS
      275, on the immune molecule content and categories in hepatocarcinoma exosomes.
      METHODS: Exosomes were isolated from the human hepatocarcinoma cell lines, HepG2
      and Hep3b, and purified by a combination technique of ultrafiltration
      centrifugation and sucrose gradient ultracentrifugation. The expressions of heat
      shock protein (HSP)70, human leukocyte antigen (HLA)-I, HLA-DR, cluster of
      differentiation (CD) 80 and NY-ESO-1 on exosomes were analyzed with
      immunoelectron microscopy and Western blotting before and after MS-275 treatment.
      Intergroup differences were statistically analyzed by the Student's paired t
      test. RESULTS: MS-275 treatment of both HepG2 and Hep3b cell types significantly
      increased the numbers of exosomes, their total protein content, and expression of
      HSP70, HLA-I and CD80 (per 100 exosomes), as compared to non-treated cells (all,
      P less than 0.01). MS-275 was also found to induce de novo expression of HLA-DR,
      but had no significant effect on NY-ESO-1 expression (P more than 0.05). The
      findings from immunoelectron microscopy confirmed those from Western blotting.
      CONCLUSION: The histone deacetylase inhibitor, MS-275, can significantly alter
      the immune molecule content and categories in exosomes of hepatocarcinoma cells.
      The differential expression profile may reflect an anti-cancer immune response
      and represent molecular targets for novel anti-hepatoma therapeutic or
      preventative strategies.

PMID- 22475148
TI  - Laccase activity in soils: considerations for the measurement of enzyme activity.
AB  - Laccases (benzenediol: oxygen oxidoreductases, EC 1.10.3.2) are copper-containing
      enzymes that catalyze the oxidative conversion of a variety of chemicals, such as
      mono-, oligo-, and polyphenols and aromatic amines. Laccases have been proposed
      to participate in the transformation of organic matter and xenobiotics as well as
      microbial interactions. Several laccase assays have been proposed and used in
      soils. Here, we show that the optimal pH conditions for the laccase substrates
      2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS, pH 3-5), 2,6
      dimethoxyphenol (4-5.5), L-3,4-dihydroxyphenylalanine (DOPA; 4-6), guaiacol (3.5
      5), 4-methylcatechol (3.5-5), and syringaldazine (5.5-7.0) are similar between
      purified laccases from Trametes versicolor and Pyricularia sp. and soil extracts;
      the substrate affinities of purified enzymes (K(M)) and soil extracts were also
      similar. The laccase assays showed specificity overlap with tyrosinase and
      ligninolytic peroxidases when hydrogen peroxide is present. The ABTS oxidation
      assay is able to reliably detect the presence of 13.5 pg mL(-1) or 0.199*10(-12)
      mol mL(-1) of T. versicolor laccase, which is three times more sensitive than the
      2,6-dimethoxyphenol-based assay and more than 40 times more sensitive than any of
      the other assays. The low molecular mass soil-derived compounds and the isolated
      fulvic and humic acids influence the laccase assays and should be removed from
      the soil extracts before measurements of the enzyme activity are performed.

PMID- 22475147
TI  - Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in
      the caudal forebrain.
AB  - BACKGROUND: A fundamental requirement for development of diverse brain regions is
      the function of local organizers at morphological boundaries. These organizers
      are restricted groups of cells that secrete signaling molecules, which in turn
      regulate the fate of the adjacent neural tissue. The thalamus is located in the
      caudal diencephalon and is the central relay station between the sense organs and
      higher brain areas. The mid-diencephalic organizer (MDO) orchestrates the
      development of the thalamus by releasing secreted signaling molecules such as
      Shh. RESULTS: Here we show that canonical Wnt signaling in the caudal forebrain
      is required for the formation of the Shh-secreting MD organizer in zebrafish. Wnt
      signaling induces the MDO in a narrow time window of 4 hours - between 10 and 14
      hours post fertilization. Loss of Wnt3 and Wnt3a prevents induction of the MDO, a
      phenotype also observed upon blockage of canonical Wnt signaling per se.
      Pharmaceutical activation of the canonical Wnt pathways in Wnt3/Wnt3a compound
      morphant embryos is able to restore the lack of the MDO. After blockage of Wnt
      signaling or knock-down of Wnt3/Wnt3a we find an increase of apoptotic cells
      specifically within the organizer primordium. Consistently, blockage of apoptosis
      restores the thalamus organizer MDO in Wnt deficient embryos. CONCLUSION: We have
      identified canonical Wnt signaling as a novel pathway, that is required for
      proper formation of the MDO and consequently for the development of the major
      relay station of the brain - the thalamus. We propose that Wnt ligands are
      necessary to maintain the primordial tissue of the organizer during somitogenesis
      by suppressing Tp53-mediated apoptosis.

PMID- 22475149
TI  - Sorption of 17alpha-ethinyl estradiol, bisphenol A and phenanthrene to different
      size fractions of soil and sediment.
AB  - The potential for negative effects caused by endocrine disrupting chemicals
      (EDCs) release into the environment is a prominent concern and numerous research
      projects have investigated possible environmental fate and toxicity. However,
      their sorption behavior by size fractions of soil and sediment has not been
      systematically represented. The sorption of bisphenol A (BPA), 17alpha-ethinyl
      estradiol (EE2) and phenanthrene (Phen) by different size fractions of soil and
      sediment were investigated. Sorption isotherms of EE2, BPA, and Phen by size
      fractions of soil (SL) and sediment (ST) were well fitted to the Freundlich
      model. The positive correlation between EE2, BPA and Phen sorption capacity
      (logK(d)) of size fractions and their organic carbon (OC) content suggests that
      OC of size fractions in SL and ST should regulate sorption, while the surface
      area (SA) of size fractions may not account for sorption of EE2, BPA and Phen.
      Each size fraction of ST had higher sorption capacity (K(d) or K(OC)) of EE2 and
      BPA than that of SL due to their difference in the polarity of organic matter
      (OM) between terrestrial and aquatic sources. Sorption capacity logK(d) for size
      fractions of SL and ST did not follow the order: clay>silt>sand due to the
      difference in OM abundance and composition between the size fractions. Large
      particle fractions of ST contributed about 80% to the overall sorption for any
      EE2, BPA, and Phen. This study was significant to evaluate size fractions of soil
      and sediment as well as their associated OM affecting EE2 and BPA sorption
      processes.

PMID- 22475150
TI  - A comparison of octanol-water partitioning between organic chemicals and their
      metabolites in mammals.
AB  - Bioaccumulation models take various elimination and uptake processes into
      account, estimating rates from chemical lipophilicity, expressed as the octanol
      water partition ratio (K(ow)). Here, we focussed on metabolism, which transforms
      parent compounds into usually more polar metabolites, thus enhancing elimination.
      The aim of this study was to quantify the change in lipophilicity of relevant
      organic pollutants undergoing various biotransformation reactions in mammals. We
      considered oxidation reactions catalyzed by three enzyme groups: cytochrome P450
      (CYP), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH). Estimated
      logK(ow) values of a selected dataset of parent compounds were compared with the
      logK(ow) of their first metabolites. The logK(ow) decreased by a factor that
      varies between 0 and -2, depending on the metabolic pathway. For reactions
      mediated by CYP, the decrease in K(ow) was one order of magnitude for
      hydroxylated and epoxidated compounds and two orders of magnitude for
      dihydroxylated and sulphoxidated xenobiotics. On the other hand, no significant
      change in lipophilicity was observed for compounds N-hydroxylated by CYP and for
      alcohols and aldehydes metabolized by ADH and ALDH. These trends could be
      anticipated by the calculus method of logK(ow). Yet, they were validated using
      experimental logK(ow) values, when available. These relationships estimate the
      extent to which the elimination of pollutants is increased by biotransformation.
      Thus, the quantification of the K(ow) reduction can be considered as a first
      necessary step in an alternative approach to anticipate biotransformation rates,
      which are hard to estimate with existing methods.

PMID- 22475151
TI  - Enchytraeidae Fridericia bulbosa as a new test species for soil ecotoxicity
      assessment.
AB  - Fridericia bulbosa (Rosa, 1887) was proposed as a new test species to assess soil
      ecotoxicity. The acute toxicity of mercury (Hg) and bromoxynil (BX) on the
      mortality of Fridericia bulbosa (F. bulbosa) in OECD soil was investigated. The
      results suggested there were statistically significant differences (p<0.05)
      between controls and treatments except lower concentration of exposure to single
      pollutant. BX was more toxic to F. bulbosa than Hg. The 14 d LC(50) values for F.
      bulbosa exposed to Hg and BX were 3.87 and 2.41 mg kg(-1), respectively. The
      effects of mixtures with single pollutants on earthworms were observed
      differently. Toxicity of Hg on earthworms was significantly influenced by the
      concentration of BX. BX was the main contributive factor of the combined toxic
      effects. It can be proved that F. bulbosa is a suitable bio-indicator to measure
      the acute toxicity of mixed pollutants in soil and the mortality of earthworms
      may be considered as a valuable and sensitive biomarker to diagnose adverse
      effect of Hg or BX in soil environment.

PMID- 22475152
TI  - Characterization of dissolved organic matter in the rhizosphere of
      hyperaccumulator Sedum alfredii and its effect on the mobility of zinc.
AB  - Pot experiments were performed to investigate the characteristics of dissolved
      organic matter (DOM) in the rhizosphere soil of hyperaccumulating ecotype (HE)
      and a non-hyperaccumulating ecotype (NHE) of Sedum alfredii and its effects on
      the mobility of zinc (Zn). DOM was fractionated using XAD resins into six
      fractions. The acid fraction was the predominant component of DOM in the
      rhizosphere of S. alfredii, with hydrophilic acid (HiA), hydrophilic base (HiB),
      and hydrophilic neutral (HiN) in HE-DOM being 1.6, 1.9, and 1.2 times higher
      respectively, as compared to NHE-DOM. ATR-FTIR results showed that DOM in the
      rhizosphere of S. alfredii consisted of a mixture of hydroxylated and carboxylic
      acids, and HE-DOM exhibited more CO, OH, CC and CO functional groups than NHE
      DOM. Resin equilibration experiment results indicated that DOM from the
      rhizosphere of both ecotypes of S. alfredii had the ability to form complexes
      with Zn, whereas the degree of complexation was significantly higher for HE-DOM
      (60%) than NHE-DOM (42%). The addition of HE-DOM significantly (P<0.05) increased
      the solubility of four Zn minerals while NHE-DOM was not as effective at the same
      concentration. It was concluded that DOM derived from the rhizosphere of
      hyperaccumulating ecotype of S. alfredii could significantly increase Zn mobility
      through the formation of soluble DOM-metal complexes, this might be one of the
      important mechanism by which S. alfredii is involved in activating metal in
      rhizosphere.

PMID- 22475153
TI  - Evaluating pharmaceuticals and caffeine as indicators of fecal contamination in
      drinking water sources of the Greater Montreal region.
AB  - We surveyed four different river systems in the Greater Montreal region, upstream
      and downstream of entry points of contamination, from April 2007 to January 2009.
      The studied compounds belong to three different groups: PPCPs (caffeine,
      carbamazepine, naproxen, gemfibrozil, and trimethoprim), hormones (progesterone,
      estrone, and estradiol), and triazine herbicides and their metabolites (atrazine,
      deethylatrazine, deisopropylatrazine, simazine, and cyanazine). In the system A,
      B, and C having low flow rate and high TOC, we observed the highest detection
      frequencies and mass flows of PPCPs compared to the other compounds, reflecting
      discharge of urban contaminations through WWTPs and CSOs. However, in River D,
      having high flow rate and low TOC, comparable frequency of detection of triazine
      and their by-products and PPCPs, reflecting cumulative loads of these compounds
      from the Great Lakes as well as persistency against natural attenuation
      processes. Considering large differences in the removal efficiencies of caffeine
      and carbamazepine, a high ratio of caffeine/carbamazepine might be an indicative
      of a greater proportion of raw sewage versus treated wastewater in surface
      waters. In addition, caffeine appeared to be a promising indicator of recent
      urban fecal contaminations, as shown by the significant correlation with FC
      (R(2)=0.45), while carbamazepine is a good indicator of cumulative persistence
      compounds.

PMID- 22475154
TI  - Trophic transfer of pyrene metabolites and nonextractable fraction from
      Oligochaete (Lumbriculus variegatus) to juvenile brown trout (Salmo trutta).
AB  - The trophic transfer of pyrene metabolites was evaluated by a 2-month exposure of
      the freshwater annelid Lumbriculus variegatus (Oligochaeta) to pyrene, followed
      by feeding to juvenile brown trout (Salmo trutta). The results obtained by
      scintillation counting (SC) proved that the pyrene metabolites produced by L.
      variegatus were transferred to juvenile S. trutta through diet. More detailed
      analyses by LC-FLD (liquid chromatography with fluorescence detection) showed
      that an unknown pyrene metabolite originating from L. variegatus was present in
      fish liver. This metabolite, although yet not properly identified, may be the
      glucose conjugate of 1-hydroxy-pyrene. This metabolite was not present in
      chromatograms of fish that were fed pyrene-spiked food pellets. In addition, the
      strongly bound tissue residue of L. variegatus, which was nonextractable neither
      by organic solvents nor by the proteolytic enzyme Proteinase K, was most likely
      not available for the fish through diet. Altogether, the present study shows that
      the metabolites of pyrene produced at low levels of the food chain may be
      potentially available for upper levels through diet, raising a concern about
      their potential toxicity to predators and supporting their inclusion in the risk
      assessment of PAHs.

PMID- 22475155
TI  - Recruitment using mobile telephones in an Irish general population sexual health
      survey: challenges and practical solutions.
AB  - BACKGROUND: Non-coverage of households without a landline telephone is a major
      concern of telephone survey researchers. Sampling mobile telephone users in
      national surveys is vital in order to gain access to the growing proportion of
      households that use mobile telephones extensively or exclusively. The complex
      logistics of conducting surveys with mobile telephones have been discussed in the
      literature. This paper outlines the actual challenges encountered during a recent
      national sexual health survey in Ireland, which utilized a mobile telephone
      sampling frame to recruit approximately half of the sample. METHOD: The 2010
      Irish Contraception and Crisis Pregnancy Survey (ICCP-2010) is a nationally
      representative sample of adults aged 18-45 years living in Ireland (n = 3002;
      1416 recruited by landline telephone and 1586 recruited by mobile telephone). The
      overall response rate for the survey was 69% (79% for the landline telephone
      strand; 61% for the mobile telephone strand). All interviews were conducted using
      computer-assisting telephone interviewing. RESULTS: During the 18-week fieldwork
      period, five main challenges relating to the use of mobile telephones were
      encountered: (1) explaining to respondents how random digit dialling works in
      relation to mobile telephones; (2) establishing the respondent's eligibility; (3)
      calling the respondent with the Caller ID blocked or withheld; (4) calling the
      respondent when they are in any number of locations or situations; and (5)
      explaining to respondents the importance of refusal conversion calls for the
      response rate calculation. Details of how the survey protocols and procedures
      were monitored and adapted throughout the study to ensure a high response rate
      are outlined. CONCLUSION: It is undeniably more challenging to recruit
      respondents using mobile telephones as opposed to landline telephones.
      Respondents are generally not familiar with being contacted on their personal
      mobile telephone for the purposes of being recruited for a research study. The
      main challenge for survey methodologists and interviewers is to devise simple
      protocols to explain to respondents why they are being contacted on a mobile
      telephone. Recommendations for survey researchers interested in using this
      methodological approach in the future are discussed.

PMID- 22475156
TI  - Synthesis of cyclopropyl glycosides and their use as novel glycosyl donors.
AB  - Methods for the synthesis of cyclopropyl glycosides and their use as glycosyl
      donors are described. Cyclopropyl glycosides containing different substituents
      were prepared by cyclopropanation of the corresponding vinyl glycosides, or by
      glycosidation of cyclopropyl alcohols that are synthesized by the Kulinkovich
      reaction. 1-Methyl- and 1-phenyl-substituted cyclopropyl glycosides undergo
      coupling to Fmoc-protected serine and threonine and to partially protected
      monosaccharides in the presence of TMS triflate to give glycosidated products.

PMID- 22475157
TI  - Synthesis of lipopolysaccharide O-antigens by ABC transporter-dependent pathways.
AB  - The O-polysaccharide (O-PS; O-antigen) of bacterial lipopolysaccharides is made
      up of repeating units of one or more sugar residues and displays remarkable
      structural diversity. Despite the structural variations, there are only three
      strategies for O-PS assembly. The ATP-binding cassette (ABC)-transporter
      dependent mechanism of O-PS biosynthesis is widespread. The Escherichia coli O9a
      and Klebsiella pneumoniae O2a antigens provide prototypes, which are
      distinguished by the fine details that link glycan polymerization and chain
      termination at the cytoplasmic face of the inner membrane to its export via the
      ABC transporter. Here, we describe the current understanding of these processes.
      Since glycoconjugate assembly complexes that utilize an ABC transporter-dependent
      pathway are widespread among the bacterial kingdom, the models described here are
      expected to extend beyond O-PS biosynthesis systems.

PMID- 22475160
TI  - Psychotherapy research and neurobiology: challenge, chance, or enrichment?
AB  - An increasing number of findings have plausible relevance for psychotherapy, but
      is the belief justified that approaching "hardware" makes methods and findings
      more reliable and valid? What can psychotherapy research contribute to
      neurobiology? What is the relative effectiveness of psychologically versus
      biologically based treatments? What is the value of neurobiological informedness
      for psychotherapists? Are there models with a potential of reducing the mind-body
      gap? What are the ethical implications? Tentative answers and illustrations are
      given, and a neural network concept for mental disorders is introduced, as is a
      simulation model for the functioning of patients that includes psychological as
      well as biological parameters. Unrealistic expectations toward neurobiology are
      questioned.

PMID- 22475159
TI  - The causal relationships between neurocognition, social cognition and functional
      outcome over time in schizophrenia: a latent difference score approach.
AB  - BACKGROUND: Social cognition has been identified as a significant construct for
      schizophrenia research with relevance to diagnosis, assessment, treatment and
      functional outcome. However, social cognition has not been clearly understood in
      terms of its relationships with neurocognition and functional outcomes. The
      present study sought to examine the empirical independence of social cognition
      and neurocognition; to investigate the possible causal structure among social
      cognition, neurocognition and psychosocial functioning. METHOD: The sample
      consists of 130 individuals diagnosed with schizophrenia. All participants were
      recruited as they were admitted to four community-based psychosocial
      rehabilitation programs. Social cognition, neurocognition and psychosocial
      functioning were measured at baseline and 12 months. The empirical independence
      of social cognition and neurocognition was tested using confirmatory factor
      analysis (CFA) and the possible causal structure among social cognition,
      neurocognition and psychosocial functioning was investigated using latent
      difference score (LDS) analysis. RESULTS: A two-factor model of social cognition
      and neurocognition fit the data very well, indicating the empirical independence
      of social cognition, whereas the longitudinal CFA results show that the empirical
      independence of neurocognition and social cognition is maintained over time. The
      results of the LDS analysis support a causal model that indicates that
      neurocognition underlies and is causally primary to social cognition, and that
      neurocognition and social cognition are causally primary to functional outcome.
      CONCLUSIONS: Social cognition and neurocognition could have independent and
      distinct upward causal effects on functional outcome. It is also suggested that
      the approaches for remediation of neurocognition and social cognition might need
      to be distinct.

PMID- 22475161
TI  - Repertory grid technique as a psychotherapy research measure.
AB  - Repertory grid technique (RGT) has received scant mention in such psychotherapy
      research texts as the Handbook of Psychotherapy and Behavior Change, even though
      its flexibility renders it, in many respects, an ideal psychotherapy research
      instrument. However, RGT has been used in numerous investigations of
      psychotherapy, encompassing a broad range of therapeutic approaches and client
      groups. The author reviews the findings of grid studies of (a) reconstruction
      during therapy, (b) client construing as a predictor of therapeutic outcome, and
      (c) the therapeutic process. Reasons for the relative lack of attention to these
      studies in the general psychotherapy research literature are considered, and
      suggestions that may help remedy this situation are made.

PMID- 22475162
TI  - Progressive changes in patients' lives after psychotherapy: which treatment
      effects support them?
AB  - The endurance of psychotherapeutic effects after conclusion of inpatient
      treatment is examined in a follow-up study of 49 patients with psychosomatic,
      neurotic, and personality disorders. The perspective is not symptomatological but
      rather relates to the concrete changes occurring in the lives of the patients
      after treatment. The investigators hypothesized that the probability of
      progressively coping with life demands depends on the extent to which patients
      have gained insight into their central psychological problems. Using the
      Heidelberg Structural Change Scale (HSCS) to gauge the extent to which patients
      succeed in gaining cognitively and emotionally definitive insight into their
      intrapsychic conflicts and the structural vulnerabilities determining their
      condition, the authors were able to confirm their hypothesis. The HSCS, compared
      with other measures, offered the only possibility of predicting progressive
      (i.e., symptomatic) changes. The authors concluded that the demands of external
      life present opportunities for therapy success to be realized as progressive
      changes and that these changes can form a basis for further positive development.

PMID- 22475163
TI  - Pretreatment expectations, interpersonal functioning, and symptoms in the
      prediction of the therapeutic alliance across supportive-expressive psychotherapy
      and cognitive therapy.
AB  - Therapeutic alliance has been a robust predictor of therapy outcome, yet little
      is known about which patient variables predict the development of an alliance
      between patient and therapist in time-limited manualized therapies. The authors
      evaluated pretreatment predictors of therapeutic alliance, controlling for
      symptom change before its assessment, using a large sample of patients treated
      with either supportive-expressive (SE) dynamic psychotherapy or cognitive
      therapy. They found that SE patients with greater pretreatment expectations of
      improvement formed better alliances with their therapist at Session 2, and
      expectations significantly predicted alliance at Session 10 for both treatment
      groups. Further, patients in the SE condition demonstrated a significant relation
      between positive expectations and growth in alliance. Women achieved better
      alliances at Session 10. Finally, hostile-dominant interpersonal problems
      significantly predicted poor alliance. Pretreatment symptom level was not
      significantly predictive of alliance.

PMID- 22475164
TI  - Enhanced adaptive capacities after brief treatment for depression.
AB  - Using data from the National Institute of Mental Health-sponsored Treatment of
      Depression Collaborative Research Program, the authors examined predictors of the
      intensity of depressive symptoms after the brief treatment of depression.
      Multilevel modeling was applied to measures of depression and stress assessed at
      termination and at 6-, 12-, and 18-month follow-ups. The slope of depression on
      stress was used to index stress reactivity. Patients with high mean levels of
      stress experienced more intense depressive symptoms, but this effect was
      moderated by patients' reports of the extent to which they had acquired enhanced
      adaptive capacities (EACs) in treatment. Patients who reported high EAC early in
      the follow-up were more resilient in the face of stress than those with low EAC.
      Greater EACs were found for patients who received psychotherapy than medication
      or placebo and, across all treatments, for patients with a stronger therapeutic
      alliance. These findings suggest that treatments should be evaluated in terms of
      their impact on patients' developing adaptive capacities as well as the reduction
      of symptomatology.

PMID- 22475165
TI  - Interpretive and supportive psychotherapies: matching therapy and patient
      personality.

PMID- 22475166
TI  - The handbook of humanistic psychology: leading edges in theory, research, and
      practice.

PMID- 22475167
TI  - Psicoanalisis focosy aperturas (psychoanalysis, focuses and openings).

PMID- 22475168
TI  - Mindfulness-based cognitive therapy for depression: a new approach to preventing
      relapse.

PMID- 22475169
TI  - Seeking Safety: A Treatment Manual for PTSD and Substance Abuse.

PMID- 22475170
TI  - Mastering relationship conflicts: discoveries in theory, research, and practice.

PMID- 22475171
TI  - A Guide to Treatments That Work (2nd ed.).

PMID- 22475173
TI  - Capture of carbon dioxide from air and flue gas in the alkylamine-appended metal
      organic framework mmen-Mg2(dobpdc).
AB  - Two new metal-organic frameworks, M(2)(dobpdc) (M = Zn (1), Mg (2); dobpdc(4-) =
      4,4'-dioxido-3,3'-biphenyldicarboxylate), adopting an expanded MOF-74 structure
      type, were synthesized via solvothermal and microwave methods. Coordinatively
      unsaturated Mg(2+) cations lining the 18.4-A-diameter channels of 2 were
      functionalized with N,N'-dimethylethylenediamine (mmen) to afford
      Mg(2)(dobpdc)(mmen)(1.6)(H(2)O)(0.4) (mmen-Mg(2)(dobpdc)). This compound displays
      an exceptional capacity for CO(2) adsorption at low pressures, taking up 2.0
      mmol/g (8.1 wt %) at 0.39 mbar and 25  degrees C, conditions relevant to removal
      of CO(2) from air, and 3.14 mmol/g (12.1 wt %) at 0.15 bar and 40  degrees C,
      conditions relevant to CO(2) capture from flue gas. Dynamic gas
      adsorption/desorption cycling experiments demonstrate that mmen-Mg(2)(dobpdc) can
      be regenerated upon repeated exposures to simulated air and flue gas mixtures,
      with cycling capacities of 1.05 mmol/g (4.4 wt %) after 1 h of exposure to
      flowing 390 ppm CO(2) in simulated air at 25  degrees C and 2.52 mmol/g (9.9 wt
      %) after 15 min of exposure to flowing 15% CO(2) in N(2) at 40  degrees C. The
      purity of the CO(2) removed from dry air and flue gas in these processes was
      estimated to be 96% and 98%, respectively. As a flue gas adsorbent, the
      regeneration energy was estimated through differential scanning calorimetry
      experiments to be 2.34 MJ/kg CO(2) adsorbed. Overall, the performance
      characteristics of mmen-Mg(2)(dobpdc) indicate it to be an exceptional new
      adsorbent for CO(2) capture, comparing favorably with both amine-grafted silicas
      and aqueous amine solutions.

PMID- 22475172
TI  - Molecular level interaction of inositol hexaphosphate with the C2B domain of
      human synaptotagmin I.
AB  - Synaptotagmin I is a synaptic vesicle membrane protein that serves as a
      multifunctional regulator during the exocytosis of neurotransmitter release. It
      contains C2A and C2B domains. The binding of Ca(2+) to the C2A domain activates
      the exocytosis of secretory vesicles, while the binding of inositol
      polyphosphates (IP4-IP6) to the C2B domain inhibits this process. To understand
      the IP6-induced inhibition of exocytosis of secretory vesicles, we determined the
      three-dimensional structure of the C2B-IP6 complex by nuclear magnetic resonance
      (NMR). In this study, we have determined the binding constant by isothermal
      titration calorimetry. The circular dichroism measurements demonstrated that IP6
      can stabilize the C2B molecule. We identified the binding site using (1)H-(15)N
      heteronuclear single-quantum coherence spectroscopy titration data and determined
      the structure of the C2B-IP6 complex using multidimensional NMR studies. This
      information will aid in the design of better pharmacological treatments for
      neurological disorders.

PMID- 22475174
TI  - Catalytic adaptive recognition of thiol (SH) and selenol (SeH) groups toward
      synthesis of functionalized vinyl monomers.
AB  - An unprecedented sustainable procedure was developed to produce functionalized
      vinyl monomers H(2)C?C(R)(FG) starting from a mixture of sulfur and selenium
      compounds as a functional group donor (FG = S or Se). The reaction serves as a
      model for efficient utilization of natural resources of sulfur feedstock in oil
      and technological sources of sulfur/selenium. The catalytic system is reported
      with amazing ability to recognize SH/SeH groups in the mixture and selectively
      incorporate them into valuable organic products via wastes-free atom-economic
      reaction with alkynes (HC=CR). Formation of catalyst active site and the
      mechanism of the catalytic reaction were revealed by joint experimental and
      theoretical study. The difference in reactivity of MU(1)- and MU(2)-type
      chalcogen atoms attached to the metal was established and was shown to play the
      key role in the action of palladium catalyst. An approach to solve a challenging
      problem of dynamically changed reaction mixture was demonstrated using adaptive
      tuning of the catalyst. The origins of the adaptive tuning effect were
      investigated at molecular level and were found to be governed by the nature of
      metal-chalcogen bond.

PMID- 22475175
TI  - Arthroscopic guided biopsy and radiofrequency thermoablation of a benign neoplasm
      of the tibial spines area: a treatment option.
AB  - BACKGROUND: Lesions located in the area of the tibial spines are rare. In most
      cases, treatment follows histological diagnosis, but when imaging and clinical
      data are considered to be "very" characteristic for benign lesions, such as
      chondroblastoma or osteoid osteoma, treatment may be performed without biopsy.
      Traditional curettage requires opening the joint, which presents a high risk of
      contamination of the joint itself and surrounding structures, such as the
      popliteal area, with possible contamination of the neurovascular bundle when
      performing curettage with the posterior approach. In this case, the re-excision
      of a local recurrence would be extremely difficult. RESULTS: We describe a
      technique using arthroscopic guidance for radiofrequency thermoablation of a
      benign lesion in the tibial spines area. We report on an illustrative case. The
      patient so treated, reported immediate relief from the pain, and after two weeks,
      was free of pain. The biopsy performed before the treatment confirmed the
      radiological diagnosis of chondroblastoma. At one year of follow-up, the patient
      is without pain, with a 0-130 degrees  range of motion, has no activity
      limitations and is apparently free of disease. CONCLUSION: This technique allows
      a radiofrequency thermoablation of a lesion in the tibial spines area and in the
      posterior tibial surface to be performed without opening the joint, monitoring
      the tibial plateau surface, probably decreasing the risk of cartilage damage.
      Unfortunately, in the case presented, the high pressure from the arthroscopy's
      pump broke the tibial plateau surface creating a communication to the tibial
      tunnel used for thermoablation.

PMID- 22475176
TI  - Microstructures and interaction analyses of phosphonium-based ionic liquids: a
      simulation study.
AB  - Simulation study of eight kinds of phosphonium-based ionic liquids (ILs) is
      reported in this work. Force fields for two kinds of alkoxyphosphonium ILs are
      proposed through systematic method and validated by the experimental densities.
      The study was conducted by molecular dynamics simulations. A connection between
      the intermolecular energy, divided into the electrostic force and the van der
      Waals force, and the experimental viscosities was found. Radial distribution
      functions (RDFs) were analyzed to probe the local organization of the liquids.
      First-shell coordination numbers are also reported by integral of RDFs from zero
      to the first minimum. In order to compare the interaction strength and position
      between ions for different kinds of ILs, the relative density distributions along
      with the distance between cation and anion are proposed. Hydrogen bond numbers
      were investigated to depict the microinteraction. We found that, although there
      are six anions in the first solvation shell of [P2,2,2,5](+), only one hydrogen
      bond could be found. Along with increase in the length of alkyl chain, the
      hydrogen bond number becomes less, and no hydrogen bond interaction is found for
      20% of the ions in [P4,4,4,14][Tf2N] In order to depict the effect of carbon
      chain length on the structure, the space distribution functions were also
      computed and compared. 

PMID- 22475177
TI  - TiCl4-promoted tandem carbonyl or imine addition and Friedel-Crafts cyclization:
      synthesis of benzo-fused oxabicyclooctanes and nonanes.
AB  - A new and convenient synthesis of benzo-fused 8-oxabicyclo[3.2.1]octane and 9
      oxabicyclo[4.2.1]nonane derivatives are described. The reaction involved a
      TiCl(4)-mediated tandem carbonyl or imine addition followed by a Friedel-Crafts
      cyclization to provide these functionalized derivatives in good to excellent
      yields and high diastereoselectivity.

PMID- 22475178
TI  - Pulse oximetry home monitoring in infants with single-ventricle physiology and a
      surgical shunt as the only source of pulmonary blood flow.
AB  - BACKGROUND: Shunt occlusion is a major cause of death in children with single
      ventricle. We evaluated whether one daily measurement of oxygen saturation at
      home could detect life-threatening shunt dysfunction. METHODS: A total of 28
      infants were included. Parents were instructed to measure saturation once daily
      and if less than or equal to 70% repeat the measurement. Home monitoring was
      defined as positive when a patient was admitted to Queen Silvia Children's
      Hospital because of saturation less than or equal to 70% on repeated measurement
      at home. A shunt complication was defined as arterial desaturation and a
      narrowing of the shunt that resulted in an intervention to relieve the
      obstruction or in death. Parents' attitude towards the method was investigated
      using a questionnaire. RESULTS: A shunt complication occurred out of hospital
      eight times in eight patients. Home monitoring was positive in five out of eight
      patients. In two patients, home monitoring was probably life saving; in one of
      them, the shunt was replaced the same day and the other had an emergency balloon
      dilatation of the shunt. In three out of eight patients, home monitoring was
      negative; one had an earlier stage II and survived, but two died suddenly at home
      from thrombotic shunt occlusion. On seven occasions in three patients home
      monitoring was positive but there was no shunt complication. The method was well
      accepted by the parents according to the results of the questionnaire.
      CONCLUSION: Home monitoring of oxygen saturation has the potential to detect some
      of the life-threatening shunt obstructions between stages I and II in infants
      with single-ventricle physiology.

PMID- 22475179
TI  - Polymorphisms in genes encoding interleukin-10 and drug metabolizing enzymes
      GSTP1, GSTT1, GSTA1 and UGT1A1 influence risk and outcome in Hodgkin lymphoma.
AB  - We genotyped 224 patients with Hodgkin lymphoma (HL) and 1056 healthy controls
      and related the risk for HL and outcome of chemotherapy treatment to
      polymorphisms in genes encoding interleukins and metabolizing enzymes by
      capillary electrophoresis. Patients with the UGT1A1 TA tandem repeat TA6/6
      genotype had a poorer overall survival (OS) (relative risk [RR] 3.63, p = 0.004),
      and patients above 40 years with the GSTA1 AA genotype had poorer event-free
      survival (EFS) (RR 4.38, p = 0.003) after chemotherapy. In patients above 40
      years, the IL-10 rs1800890 T-allele was associated with lower risk for HL (TT
      genotype vs. AA, odds ratio [OR] 0.38 [95% confidence interval 0.21-0.69], p =
      0.001; AT/TT combined genotypes vs. AA, OR 0.45 [0.27-0.74], p = 0.001). The
      GSTP1 rs1695 A-allele reduced the risk for HL (GG vs. AG, OR 0.64 [0.42-0.99], p
      = 0.04; GG vs. AG/AA combined genotypes, OR 0.70 [0.47-1.04], p = 0.07), and the
      GSTT1 deleted genotype increased the risk for HL (OR 3.17 [1.97-5.09], p < 0.001)
      regardless of age.

PMID- 22475180
TI  - Inquiry diagnosis of coronary heart disease in Chinese medicine based on symptom
      syndrome interactions.
AB  - BACKGROUND: There is a long history of coronary heart disease (CHD) diagnosis and
      treatment in Chinese medicine (CM), but a formalized description of CM knowledge
      is still unavailable. This study aims to analyze a set of CM clinical data, which
      is important and urgent. METHODS: Relative associated density (RAD) was used to
      analyze the one-way links between the symptoms or syndromes or both. RAD results
      were further used in symptom selection. RESULTS: Analysis of a dataset of
      clinical CHD diagnosis revealed some significant relationships, not only between
      syndromes but also between symptoms and syndromes. Using RAD to select symptoms
      based on different classifiers improved the accuracy of syndrome prediction.
      Compared with other traditional symptom selection methods, RAD provided a higher
      interpretability of the CM data. CONCLUSION: The RAD method is effective for CM
      clinical data analysis, particular for analysis of relationships between symptoms
      in diagnosis and generation of compact and comprehensible symptom feature
      subsets.

PMID- 22475181
TI  - Measuring the effects of alexithymia on perception of emotional vocalizations in
      autistic spectrum disorder and typical development.
AB  - BACKGROUND: The results from recent studies suggest that alexithymia, a disorder
      characterized by impairments in understanding personal experiences of emotion, is
      frequently co-morbid with autism spectrum disorder (ASD). However, the extent
      that alexithymia is associated with primary deficits in recognizing external
      emotional cues, characteristic in ASD, has yet to be determined. METHOD: Twenty
      high-functioning adults with ASD and 20 age- and intelligence-matched typical
      controls categorized vocal and verbal expressions of emotion and completed an
      alexithymia assessment. RESULTS: Emotion recognition scores in the ASD group were
      significantly poorer than in the control group and performance was influenced by
      the severity of alexithymia and the psycho-acoustic complexity of the presented
      stimuli. For controls, the effect of complexity was significantly smaller than
      for the ASD group, although the association between total emotion recognition
      scores and alexithymia was still strong. CONCLUSIONS: Higher levels of
      alexithymia in the ASD group accounted for some, but not all, of the group
      difference in emotion recognition ability. However, alexithymia was insufficient
      to explain the different sensitivities of the two groups to the effects of psycho
      acoustic complexity on performance. The results showing strong associations
      between emotion recognition and alexithymia scores in controls suggest a
      potential explanation for variability in emotion recognition in non-clinical
      populations.

PMID- 22475182
TI  - A study on the alkaline hydrolysis of isatin-beta-thiosemicarbazone by capillary
      electrophoresis with enhanced sample loadability.
AB  - An analytical potential of capillary zone electrophoresis (CZE) with enhanced
      sample loadability (a 200nL injection volume) in determination of alkaline
      hydrolysis products of isatin-beta-thiosemicarbazone (IBT), a compound with
      important biological activity, has been studied. The CZE separation conditions
      for a complete resolution of transformation products, i.e. 2
      aminophenylglyoxalate, 2-(2-aminophenyl)-2-semicarbazonoethane, anthranilate and
      E-Z geometric isomers of 2-(2-aminophenyl)-2-thiosemicarbazonoethane, have been
      optimized. CZE separations with UV detection at 240 nm were performed using
      glycine running buffer at high pH (9.2) and containing an uncharged beta
      cyclodextrin as a complexing agent. High sensitivity (with detection limits
      ranging from 0.1 to 1.2 MUM), good repeatability (RSD of migration times less
      than 0.4% and 0.4-3.4% RSD of peak areas) and linearity over two orders of
      magnitude were achieved for the compounds studied. The employed CZE method,
      characterized by simple sample handling (only dilution step needed) and total
      analysis time of less than 15 min, has been applied successfully to time
      monitoring of the transformation of IBT in alkaline media. Under optimized CZE
      conditions, the effect of pH of reaction media, implemented by different
      concentration of NaOH (0.1-100mM), on the course of the alkaline hydrolysis of
      IBT was studied in this respect, as well.

PMID- 22475183
TI  - Study on the use of boromycin as a chiral selector in capillary electrophoresis.
AB  - The first application of boromycin as a chiral selector in capillary
      electrophoresis is described. Given boromycin's insolubility in water, a non
      aqueous background electrolyte based on methanol was used for enantiomeric
      discrimination of selected chiral primary amines (alpha-methylbenzylamine, R,S
      tryptophanol, R,S-norepinephrine, R,S-octopamine, R,S-p-hydroxynorephedrine and
      R,S-2-amino-1-phenylethanol). A basic study of experimental conditions including
      the influence of boromycin concentration, the composition and concentration of
      background electrolyte and also the influence of different organic solvents was
      performed. The best separation condition was 75 mM Tris/50mM boric acid in
      methanol, pHws 9.0, with a positive separation voltage. The enantiomeric
      separation of the primary amines was achieved within 14 min with resolution
      values greater than 1.5 for the majority of the studied analytes.

PMID- 22475184
TI  - Low crosslinking imprinted coatings based on liquid crystal for capillary
      electrochromatography.
AB  - Low loading capacity is the main problem of molecularly imprinted stationary
      phase, which is attributed to the high level of crosslinking restricting
      distortion phenomena of polymer backbone in molecular imprinting. A new approach
      based on liquid crystal with recognition ability is demonstrated for synthesis of
      molecularly imprinted polymer coatings in a low level of crosslinking. The
      resulting low crosslinking (20%) open-tubular imprinted capillary was able to
      separate enantiomers by means of capillary electrochromatography. The resolution
      of enantiomer separation achieved on the (S)-amlodipine-imprinted capillary was
      up to 6.36 in less than 2.5 min. The strong recognition ability with a
      selectivity factor of 1.81 and high column performance of template (up to 23,300
      plates/m) were obtained. Performance of imprinting comparable to that recorded in
      conventional MIP stationary phase was observed. The liquid crystal MIP coatings
      were also prepared using either (S)-naproxen or (S)-ofloxacin as template
      molecule. The resolutions of enantiomers separation were 1.41 and 1.55,
      respectively. The results illustrate that the synthesis of low crosslinking MIP
      coatings based on liquid crystal is not only an experimental-simplified process
      of high performance, but also an approach to produce chiral stationary phase
      comparable to other chiral stationary phases.

PMID- 22475185
TI  - Preparation of two novel monobrominated 2-(2',4'-dihydroxybenzoyl)-3,4,5,6
      tetrachlorobenzoic acids and their separation from crude synthetic mixtures using
      vortex counter-current chromatography.
AB  - The present work describes the preparation of two compounds considered to be
      likely precursors of an impurity present in samples of the color additives D&C
      Red No. 27 (Color Index 45410:1) and D&C Red No. 28 (Color Index 45410, phloxine
      B) submitted to the U.S. Food and Drug Administration for batch certification.
      The two compounds, 2-(2',4'-dihydroxy-3'-bromobenzoyl)-3,4,5,6-tetrachlorobenzoic
      acid (3BrHBBA) and its 5'-brominated positional isomer (5BrHBBA), both not
      reported previously, were separated from synthetic mixtures by vortex counter
      current chromatography (VCCC). 3BrHBBA was prepared by chemoselective ortho
      bromination of the dihydroxybenzoyl moiety. Two portions of the obtained
      synthetic mixture, 200mg and 210 mg, respectively, were separated by VCCC using
      two two-phase solvent systems that consisted of hexane-ethyl acetate-methanol
      aqueous 0.2% trifluoroacetic acid (TFA) in the volume ratios of 8:2:5:5 and
      7:3:5:5, respectively. These separations produced 35 mg and 78 mg of 3BrHBBA,
      respectively, each product of over 98% purity by HPLC at 254 nm. 5BrHBBA was
      prepared by monobromination of the dihydroxybenzoyl moiety in the presence of
      glacial acetic acid. To separate the obtained synthetic mixture, VCCC was
      performed in the pH-zone-refining mode with a solvent system consisting of hexane
      ethyl acetate-methanol-water (6:4:5:5, v/v) and with TFA used as the retainer
      acid and aqueous ammonia as the eluent base. Separation of a 1-g mixture under
      these conditions resulted in 142 mg of 5BrHBBA of ~ 99% purity by HPLC at 254 nm.
      The isolated compounds were characterized by high-resolution mass spectrometry
      and proton nuclear magnetic resonance spectroscopy.

PMID- 22475186
TI  - Effect of anti-inflammatory drugs on colibacillosis lesions in broilers after
      Infectious Bronchitis Virus and subsequent Escherichia coli infection.
AB  - BACKGROUND: In case of persistent and sterile inflammation, anti-inflammatory
      drugs should be considered as first choice treatment instead of antibiotics.
      OBJECTIVE: To assess the effect of anti-inflammatory drugs on lesions due to
      colibacillosis. ANIMALS & METHODS: Five groups of day-old broilers of 15 birds
      each were housed in isolators and were inoculated at 29 days of age with
      Infectious Bronchitis Virus strain M41 by the oculo-nasal and IT (intratracheal)
      route (10(5.4) EID(50) (egg infectious dosis 50)/broiler) and at 33 days of age
      with Escherichia coli strain 506 by the IT route (10(7.6) colony forming
      units/broiler). Broilers of four groups were treated from day 28 up to and
      including day 39 orally on a daily basis with either carbasalate calcium (4 *
      12.5 mg), meloxicam (2 * 0.5 mg), acetaminophen (4 * 2.5 mg), or dexamethasone (1
      * 1.0 mg). The fifth group was placebo-medicated. At 40 days of age, the
      experiment was ended and at post-mortem examination, colibacillosis lesions were
      assessed. RESULTS: All broilers in the dexamethasone group died. This mortality
      exceeded significantly (p < 0.05) that of the other groups in which mortality
      ranged from 2 to 5. Mean lesion score of surviving broilers of medicated groups
      ranged from 5.3 to 5.8 compared to 3.9 in the placebo group and did not differ
      significantly between groups. CONCLUSION: None of the anti-inflammatory drugs had
      a positive effect on colibacillosis lesions. CLINICAL IMPORTANCE: Anti
      inflammatory drugs cannot be considered as an alternative for antibiotic
      treatment.

PMID- 22475187
TI  - Prevalence of syphilis infection in different tiers of female sex workers in
      China: implications for surveillance and interventions.
AB  - BACKGROUND: Syphilis has made a dramatic resurgence in China during the past two
      decades and become the third most prevalent notifiable infectious disease in
      China. Female sex workers (FSWs) have become one of key populations for the
      epidemic. In order to investigate syphilis infection among different tiers of
      FSWs, a cross-sectional study was conducted in 8 sites in China. METHODS: Serum
      specimens (n = 7,118) were collected to test for syphilis and questionnaire
      interviews were conducted to obtain socio-demographic and behavioral information
      among FSWs recruited from different types of venues. FSWs were categorized into
      three tiers (high-, middle- and low-tier FSWs) based on the venues where they
      solicited clients. Serum specimens were screened with enzyme-linked immunosorbent
      assay (ELISA) for treponemal antibody followed by confirmation with non
      treponemal toluidine red unheated serum test (TRUST) for positive ELISA specimens
      to determine syphilis infection. A logistic regression model was used to
      determine factors associated with syphilis infection. RESULTS: Overall syphilis
      prevalence was 5.0% (95%CI, 4.5-5.5%). Low-tier FSWs had the highest prevalence
      (9.7%; 95%CI, 8.3-11.1%), followed by middle-tier (4.3%; 95%CI, 3.6-5.0%, P <
      0.001) and high-tier FSWs (2.2%; 95%CI, 1.6-2.9%, P < 0.001). Factors
      independently associated with syphilis infection included older age, lower
      education level, geographic location, lower tier of typology, and injection drug
      use. CONCLUSIONS: This multi-site survey showed a high prevalence of syphilis
      infection among FSWs and substantial disparities in syphilis prevalence by the
      tier of FSWs. The difference in syphilis prevalence is substantial between
      different tiers of FSWs, with the highest rate among low-tier FSWs. Thus, current
      surveillance and intervention activities, which have low coverage in low-tier
      FSWs in China, should be further examined.

PMID- 22475188
TI  - Reply to the Response to The statistics of skin impedance.

PMID- 22475189
TI  - Causes and consequences of the deficiencies of the lower limbs in the Republic of
      Guinea.
AB  - PURPOSE: According to the last general census of 1996, the deficiency of lower
      limbs is the main cause of handicap in the Republic of Guinea. The objective of
      this study that took place in 2008 in Conakry is to analyze the main causes of
      this phenomenon, as well as to understand the reasons of their increase within
      the Guinean capital. METHOD: Our survey covered 244 Guineans out of which 170 men
      and 74 women were living in Conakry, aged between 10 and 68 years old (+/-12,6).
      RESULTS: The main causes of the deficiencies are the poliomyelitis after-effects
      (40%), as well as other risk factors such as the road accidents and the failure
      of the health system. Whatever the nature of the deficiencies, their compensation
      is mainly based on the technical supports such as tricycles and wheelchairs.
      However, they are distributed in a random way and without any medical follow-up.
      CONCLUSION: The orthopedic care in the Republic of Guinea is insufficient and
      inadequate. Hence, certain individuals who need it the most do not receive it.
      This type of care is not always helpful and sometimes harmful to the health of
      the disabled persons.

PMID- 22475190
TI  - Assessment of the performance of MP2 and MP2 variants for the treatment of
      noncovalent interactions.
AB  - For many years, MP2 served as the principal method for the treatment of
      noncovalent interactions. Until recently, this was the only technique that could
      be used to produce reasonably accurate binding energies, with binding energy
      errors generally below ~35%, at a reasonable computational cost. The past decade
      has seen the development of many new methods with improved performance for
      noncovalent interactions, several of which are based on MP2. Here, we assess the
      performance of MP2, LMP2, MP2-F12, and LMP2-F12, as well as spin component scaled
      variants (SCS) of these methods, in terms of their abilities to produce accurate
      interaction energies for binding motifs commonly found in organic and
      biomolecular systems. Reference data from the newly developed S66 database of
      interaction energies are used for this assessment, and a further set of 38
      complexes is used as a test set for SCS methods developed herein. The strongly
      basis set-dependent nature of MP2 is confirmed in this study, with the SCS
      technique greatly reducing this behavior. It is found in this work that the spin
      component scaling technique can effectively be used to dramatically improve the
      performance of MP2 and MP2 variants, with overall errors being reduced by factors
      of about 1.5-2. SCS versions of all MP2 variants tested here are shown to give
      similarly accurate overall results.

PMID- 22475191
TI  - Expression of a murine homolog of apoptosis-inducing human IL-24/MDA-7 in murine
      tumors fails to induce apoptosis or produce anti-tumor effects.
AB  - Expression of human interleukin (IL)-24 in tumors achieved anti-tumor effects
      through apoptosis. IL-24 also induced secretion of proinflammatory cytokines,
      suggesting the role in immunity. We showed that murine IL-24 transcripts started
      from the second initiation codon and that expressed mIL-24 in tumors failed to
      induce apoptosis. Proliferation of murine cells expressing mIL-24 was the same as
      that of the parent cells and inoculation of the mIL-24-expressing tumors into
      syngeneic mice did not produce anti-tumor effects. Secretory mIL-24 did not
      induce the expression of the IL-6, TNF-alpha or IFN-gamma gene in spleen cells.
      Expression of mIL-24 receptor subunits, IL-22R and IL-20R1, was undetectable in
      spleen cells even though they were stimulated by anti-CD3, anti-CD40 antibody or
      concanavalin A. Transduction of murine tumors with adenoviruses expressing the
      human IL-24 gene however suppressed the viability and decreased the tumor growth.
      These data suggest that mIL-24 is functionally irrelevant to the human
      counterpart.

PMID- 22475192
TI  - Symptom distress in advanced chronic organ failure: disagreement among patients
      and family caregivers.
AB  - BACKGROUND: Proxy reporting is frequently used to assess symptom distress of
      patients with advanced chronic organ failure. The aim of the present cross
      sectional study was to examine agreement in severity of symptom distress,
      presence of symptom-related interventions, and satisfaction with medical
      treatment among patients with advanced chronic obstructive pulmonary disease
      (COPD), chronic heart failure (CHF) and chronic renal failure (CRF) and their
      family caregivers. METHODS: Outpatients with advanced COPD (n=73), CHF (n=45) and
      CRF (n=41) and their family caregivers rated severity of physical and
      psychological symptoms experienced by the patient using Visual Analogue Scales
      (VAS). The presence of symptom-related interventions was recorded by patients and
      family caregivers. Finally, patients and family caregivers rated satisfaction
      with medical treatment of the patient using VAS. Agreement was determined using
      intraclass correlation coefficients (ICC) for continuous variables and Cohen's
      kappa for categorical variables. RESULTS: Family caregivers reported a higher
      number of symptoms than patients (mean [standard deviation; SD]: 8.2 [3.5] versus
      7.3 [3.6], respectively [p<0.0005]). For most symptoms, agreement about severity
      between patients and family caregivers was moderate (ICC: 0.41-0.60). Agreement
      about satisfaction with medical treatment was fair (ICC [95% confidence interval;
      CI]: 0.21 [0.05-0.35]). Agreement was poor to moderate for presence of symptom
      related interventions (kappa: -0.03-0.54). CONCLUSIONS: Studies using proxy
      reporting reflect the views of proxies and do not accurately represent the
      patients' experience. For clinical care, it's important to pay attention to the
      perception from the patient as well as the perception from the family caregiver
      of symptom distress, presence of symptom-related interventions, and satisfaction
      with treatment.

PMID- 22475193
TI  - Detecting and managing depressed patients: palliative care nurses' self-efficacy
      and perceived barriers to care.
AB  - BACKGROUND: Depression is a highly prevalent yet under-recognized and under
      treated psychiatric illness in patients receiving palliative care. Nurses are the
      front-line health care professionals in these settings and are well-positioned to
      detect depressive symptoms and initiate pathways to care. Previous research
      suggests, however, that nurses' confidence and skills in relation to this task
      are low, and there appear to be a number of barriers within these settings that
      may impede nurses' engagement in this process. METHODS: To further investigate
      these factors, a quantitative study was carried out with 69 palliative care
      nurses from three palliative care services in Australia. RESULTS: A number of
      issues were identified, including the need for further training in the signs and
      symptoms of depression, issues around discussing depression with patients and
      their family members, and difficulty differentiating depressive symptoms from
      grief. CONCLUSION: These findings provide insight into specific areas in which
      palliative care nurses would benefit from further training to improve detection
      rates for depression in this vulnerable population.

PMID- 22475194
TI  - "Tu Souffres, Cela Suffit": the compassionate hospital.
AB  - The authors propose that the characteristics of personal (individual) compassion
      may be extrapolated to the concept of corporate (organizational) compassion.
      Modern health care facilities attract staff members who are able to exercise
      varying degrees of compassion in their busy daily routines. However, little
      discussion has taken place on how health care organizations might best harness
      and integrate aspects of individual compassion to create an organization with
      compassion as a core value. We define three characteristics of a "compassionate
      hospital" as 1) the presence of a healing environment, 2) a sense of connection
      among people, and 3) a sense of purpose and identity. We suggest how a "top down"
      focus on compassion as a core value by clinical leaders could maximize the
      compassion of health care workers, and reduce the suffering expressed and/or
      experienced by health care workers and patients in today's health care
      facilities. The compassionate hospital concept is intended to act as a
      proposition for health policy researchers and decision-makers in health care so
      as to reduce the suffering of sick patients, and to restore a sense of well
      being, meaning, and purpose among health care workers.

PMID- 22475195
TI  - Internal medicine trainee self-assessments of end-of-life communication skills do
      not predict assessments of patients, families, or clinician-evaluators.
AB  - PURPOSE: To investigate the strength of association between trainees' self
      assessments of the quality of their end-of-life communication skills and the
      assessments of their patients, patients' families, and clinician-evaluators.
      METHODS: As part of a randomized trial, pre-intervention survey data were
      collected at two sites from internal medicine trainees and their patients,
      patients' families, and clinician-evaluators. In this observational analysis,
      comparisons using regression analysis were made between (1) trainees' scores on a
      scale of perceived competence at communication about end-of-life care and (2)
      patients', families', and clinician-evaluators' scores on a questionnaire on the
      quality of end-of-life communication (QOC). Secondary analyses were performed
      using topic-focused subscales of these measures. RESULTS: Internal medicine
      trainees (143) were studied with both self-assessment and external assessments.
      No significant associations were found between trainee perceived competence
      scores and primary outcome measures (p>0.05). Of the 12 secondary subscale
      analyses, trainees' self-ratings were significantly associated with external
      assessments for only one comparison, but the association was in the opposite
      direction with increased trainee ratings being significantly associated with
      decreased family ratings on "treatment discussions." We also examined the
      correlation between ratings by patients, family, and clinician-evaluators, which
      showed significant correlations (p<0.05) for 7 of 18 comparisons (38.9%).
      CONCLUSIONS: Trainee self-evaluations do not predict assessments by their
      patients, patients' families, or their clinician-evaluators regarding the quality
      of end-of-life communication. Although these results should be confirmed using
      the same measures across all raters, in the meantime efforts to improve
      communication about end-of-life care should consider outcomes other than
      physician self-assessment to determine intervention success.

PMID- 22475196
TI  - The life cycle of Australapatemon magnacetabulum (Digenea: Strigeidae) from
      Northwestern Argentina.
AB  - The life cycle of Australapatemon magnacetabulum Dubois, 1988 was resolved
      experimentally. Planorbid snails Biomphalaria tenagophila (d'Orbigny, 1835)
      collected in a small pond at the confluence of the San Lorenzo and Arias Rivers,
      near Salta City, Province of Salta, Argentina, were found to be shedding
      furcocercous cercariae possessing 4 pairs of penetration glands, 1 pair of
      unpigmented eyespots, 6 pairs of flame cells in the body, and 1 pair in the tail
      stem. Metacercariae were found encysted in naturally, and experimentally, exposed
      leeches Helobdella adiastola Ringuelet, 1972, Helobdella triserialis (Blanchard,
      1849), Haementeria eichhorniae Ringuelet 1978, and Haementeria sp., and within
      their sporocysts in naturally infected planorbid intermediate hosts. Sexually
      mature adults were recovered from domestic chicks and a duck 8-28 days
      postexposure by metacercariae from leeches. The identification of the species was
      based upon the characteristic large ventral sucker and a genital cone, crossed by
      a hermaphroditic duct with internal folds, occupying approximately a 1/4 to 1/5
      of the hindbody.

PMID- 22475198
TI  - Toward temperature-dependent coarse-grained potentials of side-chain interactions
      for protein folding simulations. II. Molecular dynamics study of pairs of
      different types of interactions in water at various temperatures.
AB  - By means of molecular dynamics simulations of 15 pairs of molecules selected to
      model the interactions of nonpolar, nonpolar and polar, nonpolar and charged,
      polar, and polar and charged side chains in water, we determined the potentials
      of mean force (PMFs) of pairs of interacting molecules in water as functions of
      distance between the interacting particles or their distance and orientations at
      three temperatures: 283, 323, and 373 K, respectively. The systems were found to
      fall into the following four categories as far as the temperature dependence of
      the PMF is concerned: (i) pairs for which association is entropy-driven, (ii)
      pairs for which association is energy-driven, (iii) pairs of positively charged
      solute molecules, for which association is energy-driven with unfavorable entropy
      change, and (iv) the remaining systems for which temperature dependence is weak.
      For each pair of PMFs, entropic and energetic contributions have been discussed.

PMID- 22475199
TI  - Balloon atrial septostomy performed "out-of-hours": effects on the outcome.
AB  - BACKGROUND: Balloon atrial septostomy is a common palliative procedure in
      neonates with cyanotic congenital heart disease with restricted interatrial blood
      flow. Despite its advantages, balloon atrial septostomy is not a risk-free
      procedure and can be associated with numerous complications. The objective of
      this study is to determine whether the performance of this procedure out-of-hours
      has a significant impact on the incidence of adverse outcome measures. METHODS
      AND RESULTS: A total of 106 neonates who underwent balloon atrial septostomy
      between 2004 and 2010 were studied retrospectively. In all, 64 infants had the
      procedure performed within routine hours (9 am to 6 pm), whereas 42 neonates
      underwent the procedure out-of-hours (6:01 pm to 8:59 am). Procedure-related
      complications occurred in 32 infants (30.2%), which included 12 out of 64 (18.8%)
      infants in the routine-hours group and 20 out of 42 (47.6%) in the out-of-hours
      group. During further follow-up after surgery and including both major and minor
      adverse events, seven more infants (10.9%) suffered complications after balloon
      atrial septostomy in the routine-hours group and four more infants (9.5%)
      suffered complications in the out-of-hours group. This totalled the complication
      rate in the routine-hours group to 19 infants (29.7%) and 24 infants (57.1%) in
      the out-of-hours group (p = 0.001). A higher overall mortality rate was also
      noted in the out-of-hours group. CONCLUSIONS: Balloon atrial septostomy performed
      out-of-hours produced higher complication rates as opposed to balloon atrial
      septostomy performed during routine hours. Only essential cases should be
      undertaken at night, and all other cases should be deferred to the daytime to
      limit unnecessary adverse complication.

PMID- 22475200
TI  - Superior dispersion of highly reduced graphene oxide in N,N-dimethylformamide.
AB  - Here, we report the effect of temperature on the extent of hydrazine reduction of
      graphene oxide in N,N-dimethylformamide (DMF)/water (80/20 v/v) and the
      dispersibility of the resultant graphene in DMF. The highly reduced graphene
      oxide (HRG) had a high C/O ratio and good dispersibility in DMF. The good
      dispersibility of HRGs is due to the solvation effect of DMF on graphene sheets
      during the hydrazine reduction, which diminishes the formation of irreversible
      graphene sheet aggregates. The dispersibility of the HRGs was varied from 1.66 to
      0.38 mg/mL when the reduction temperature increased from 25  degrees C to 80 
      degrees C. The dispersibility of the HRGs was inversely proportional to the
      electrical conductivity of the HRGs, which varied from 17,400 to 25,500 S/m. The
      relationships between the C/O ratio, electrical conductivity, and dispersibility
      of the HRGs were determined and these properties were found to be easily
      controlled by manipulating the reduction temperature.

PMID- 22475201
TI  - Study and enhance the photovoltaic properties of narrow-bandgap Cu2SnS3 solar
      cell by p-n junction interface modification.
AB  - Photovoltaic properties of narrow-bandgap Cu(2)SnS(3) (CTS) are studied for the
      first time by employing a superstrate solar cell structure of fluorine-doped tin
      oxide (FTO) glass/TiO(2)/In(2)S(3)/CTS/Mo. The structural, optical, and
      electronic characteristics of the CTS make it great potential as bottom cell
      absorber material for low-cost thin film tandem solar cell application.
      Furthermore, by inserting a thin low temperature deposited In(2)S(3) layer
      between the In(2)S(3) buffer layer and the CTS absorber layer, an enhancement in
      the performance of the solar cell can be achieved, leading to about 75%
      improvement (eta=1.92%) over the unmodified device (eta=1.10%).

PMID- 22475202
TI  - Developmental pathways to conduct disorder: implications for future directions in
      research, assessment, and treatment.
AB  - Research has indicated that there are several common pathways through which
      children and adolescents develop conduct disorder, each with different risk
      factors and each with different underlying developmental mechanisms leading to
      the child's aggressive and antisocial behavior. The current article briefly
      summarizes research on these pathways, including one that onsets in adolescence
      and seems to be an exaggeration of normal adolescent rebellion against authority.
      The other two pathways typically involve conduct problems that onset early in
      childhood but differ on whether the child shows significant levels of callous
      unemotional traits or whether the child shows significant problems in emotional
      and behavioral regulation. Important directions for future research on these
      pathways are highlighted, as well as implications of these pathways for assessing
      and diagnosing children and adolescents with conduct disorder. In particular,
      diagnostic criteria should recognize the importance of callous-unemotional traits
      for distinguishing a distinct subgroup of youths with the disorder. Finally,
      implications for the prevention and treatment of conduct disorder are discussed,
      especially the need for interventions that are comprehensive and individualized
      to the characteristics of children and adolescents in the various developmental
      pathways.

PMID- 22475203
TI  - Diagnostic tools to monitor udder health in dairy goats.
AB  - This article discusses the use of somatic cell count (SCC) and bacteriological
      culture (BC) as monitoring tools to assess the udder health situation of dairy
      goats. Both SCC and BC can be applied for milk samples from individual goats or
      at bulk milk samples. The causative agent of primary concern in the dairy goat
      industry is Staphylococcus aureus. This pathogen strongly increases goat milk
      SCC. The SCC is therefore a useful test to detect S. aureus-infected goats.
      However, several non-infectious factors, most importantly the stage of lactation,
      also influence SCC, complicating the interpretation of this test. BC has a low
      sensitivity for the detection of S. aureus-infected goats, but is a valuable tool
      to obtain information on which bacterial species are responsible for udder health
      problems in a herd.

PMID- 22475204
TI  - Inhibition of VEGF expression in A431 and MDA-MB-231 tumour cells by cationic
      lipid-mediated siRNA delivery.
AB  - In order to promote siRNA transfer in tumour cells, we used an original cationic
      lipid, synthesized in our laboratory, dimethyl-hydroxyethyl-aminopropane
      carbamoyl-cholesterol (DMHAPC-Chol). Liposomes were prepared from this lipid and
      dioleoylphosphatidylethanolamine (DOPE) in equimolar proportion. Its transfecting
      capacity was evaluated using ELISA, cell cytometry, and RT-PCR in estimating the
      silencing effect of VEGF siRNA. This liposome efficiently delivered VEGF siRNA in
      two human cancer cell lines abundantly secreting VEGF, A431 and MDA-MB-231.
      Results showed that 50 nM of VEGF siRNA carried by DMHAPC-Chol/DOPE liposomes
      already silenced more than 90% of VEGF in these cells. A comparative study with
      two commercial carriers indicated that the inhibition induced by VEGF siRNA
      transported by cationic DMHAPC-Chol/DOPE liposomes was comparable to that induced
      by INTERFERin and better than lipofectamine 2000. Moreover, a transfection by a
      GFP plasmid followed by a GFP siRNA showed that DMHAPC-Chol/DOPE liposomes
      compared to lipofectamine were less efficient for plasmid but better for siRNA
      transport. Following one of our previous works concerning cell delivery of
      plasmid ( Percot et al., 2004 ), the main interest of results presented here
      resides in the double potential of DMHAPC-Chol/DOPE liposomes to deliver little
      sized siRNA as well as large nucleic acids in cells.

PMID- 22475205
TI  - Correlation of renin angiotensin and aldosterone system activity with
      subcutaneous and visceral adiposity: the framingham heart study.
AB  - BACKGROUND: Animal studies suggest that local adipocyte-mediated activity of the
      renin-angiotensin-aldosterone system (RAAS) contributes to circulating levels,
      and may promote the development of obesity-related hypertension in rodents.
      METHODS: We examined relations of systemic RAAS activity, as assessed by
      circulating plasma renin activity (PRA), serum aldosterone level, and
      aldosterone:renin ratio (ARR), with specific regional adiposity measures in a
      large, community-based sample. Third Generation Framingham Heart Study
      participants underwent multidetector computed tomography assessment of SAT and
      VAT volumes during Exam 1 (2002 and 2005). PRA and serum aldosterone were
      measured after approximately 10 minutes of supine rest; results were log
      transformed for analysis. Correlation coefficients between log-transformed RAAS
      measures and adiposity measurements were calculated, adjusted for age and sex.
      Partial correlations between log-transformed RAAS measures and adiposity
      measurements were also calculated, adjusted for standard CVD risk factors.
      RESULTS: Overall, 992 women and 897 men were analyzed (mean age 40 years; 7%
      hypertension; 3% diabetes). No associations were observed with SAT (renin r =
      0.04, p = 0.1; aldosterone r = -0.01, p = 0.6) or VAT (renin r = 0.03, p = 0.2;
      aldosterone r = -0.03, p = 0.2). Similar results were observed for ARR, in sex
      stratified analyses, and for BMI and waist circumference. Non-significant partial
      correlations were also observed in models adjusted for standard cardiovascular
      risk factors. CONCLUSIONS: Regional adiposity measures were not associated with
      circulating measures of RAAS activity in this large population-based study.
      Further studies are required to determine whether adipocyte-derived RAAS
      components contribute to systemic RAAS activity in humans.

PMID- 22475206
TI  - Rationale and design of the RESOLVE trial: lanreotide as a volume reducing
      treatment for polycystic livers in patients with autosomal dominant polycystic
      kidney disease.
AB  - BACKGROUND: A large proportion of patients with autosomal dominant polycystic
      kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when
      liver volume increases. The somatostatin analogue lanreotide has proven to reduce
      liver volume in patients with polycystic liver disease. However, this study also
      included patients with isolated polycystic liver disease (PCLD). The RESOLVE
      trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with
      symptomatic polycystic livers. In this study we present the design of the RESOLVE
      trial. METHODS/DESIGN: This open-label clinical trial evaluates the effect of 6
      months of lanreotide in ADPKD patients with symptomatic polycystic livers.
      Primary outcome is change in liver volume determined by computerised tomography
      volumetry. Secondary outcomes are changes in total kidney volume, kidney
      intermediate volume and renal function. Furthermore, urinary (NGAL, alpha1
      microglobulin, KIM-1, H-FABP, MCP-1) and serum (fibroblast growth factor 23)
      biomarkers associated with ADPKD disease severity are assessed to investigate
      whether these biomarkers predict treatment responses to lanreotide. Moreover,
      safety and tolerability of the drug in ADPKD patients will be assessed.
      DISCUSSION: We anticipate that lanreotide is an effective therapeutic option for
      ADPKD patients with symptomatic polycystic livers and that this trial aids in the
      identification of patient related factors that predict treatment response. TRIAL
      REGISTRATION NUMBER: Clinical trials.gov NCT01354405.

PMID- 22475207
TI  - Synergistic effect of Pb(2+) and phosphatidylinositol 4,5-bisphosphate on C2
      domain-membrane interactions.
AB  - Ca(2+)-responsive C2 domains are peripheral membrane modules that target their
      host proteins to anionic membranes upon binding Ca(2+) ions. Several C2 domain
      containing proteins, such as protein kinase C isoenzymes (PKCs), have been
      identified as molecular targets of Pb(2+), a known environmental toxin. We
      demonstrated previously that the C2 domain from PKCalpha (C2alpha) binds Pb(2+)
      with high affinity and undergoes membrane insertion in the Pb(2+)-complexed form.
      The objective of this work was to determine the effect of phosphatidylinositol
      4,5-bisphosphate (PIP(2)) on the C2alpha-Pb(2+) interactions. Using nuclear
      magnetic resonance (NMR) experiments, we show that Pb(2+) and PIP(2)
      synergistically enhance each other's affinity for C2alpha. Moreover, the affinity
      of C2alpha for PIP(2) increases upon progressive saturation of the metal-binding
      sites. Combining the NMR data with the results of protein-to-membrane Forster
      resonance energy transfer and vesicle sedimentation experiments, we demonstrate
      that PIP(2) can influence two aspects of C2alpha-Pb(2+)-membrane interactions:
      the affinity of C2alpha for Pb(2+) and the association of Pb(2+) with the anionic
      sites on the membrane. Both factors may contribute to the toxic effect of Pb(2+)
      resulting from the aberrant modulation of PKCalpha activity. Finally, we propose
      a mechanism for Pb(2+) outcompeting Ca(2+) from membrane-bound C2alpha.

PMID- 22475208
TI  - Concise synthesis of alpha-trisubstituted amines from ketones using N
      methoxyamines.
AB  - Three-component allylation and cyanation utilizing a ketone and an N-methoxyamine
      are reported. The high nucleophilicity of the N-methoxyamine and high
      electrophilicity of the corresponding iminium ion enable the concise synthesis of
      alpha-trisubstituted amines in a single step.

PMID- 22475210
TI  - Time-course of antibody responses against Coxiella burnetii following acute Q
      fever.
AB  - Large outbreaks of Q fever in The Netherlands have provided a unique opportunity
      for studying longitudinal serum antibody responses in patients. Results are
      presented of a cohort of 344 patients with acute symptoms of Q fever with three
      or more serum samples per patient. In all these serum samples IgM and IgG against
      phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A
      mathematical model of the dynamic interaction of serum antibodies and pathogens
      was used in a mixed model framework to quantitatively analyse responses to C.
      burnetii infection. Responses show strong heterogeneity, with individual serum
      antibody responses widely different in magnitude and shape. Features of the
      response, peak titre and decay rate, are used to characterize the diversity of
      the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and
      2) reveals a class of patients with high IgG peak titres that decay slowly and
      may represent potential chronic cases. When combining the results of mixture
      analysis into an odds score, it is concluded that not only high IgG phase 1 may
      be predictive for chronic Q fever, but also that high IgG phase 2 may aid in
      detecting such putative chronic cases.

PMID- 22475209
TI  - Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in
      mice supports a beneficial effect of dietary curcumin in Huntington's disease.
AB  - BACKGROUND: No disease modifying treatment currently exists for Huntington's
      disease (HD), a fatal neurodegenerative disorder characterized by the formation
      of amyloid-like aggregates of the mutated huntingtin protein. Curcumin is a
      naturally occurring polyphenolic compound with Congo red-like amyloid binding
      properties and the ability to cross the blood brain barrier. CAG140 mice, a knock
      in (KI) mouse model of HD, display abnormal aggregates of mutant huntingtin and
      striatal transcriptional deficits, as well as early motor, cognitive and
      affective abnormalities, many months prior to exhibiting spontaneous gait
      deficits, decreased striatal volume, and neuronal loss. We have examined the
      ability of life-long dietary curcumin to improve the early pathological phenotype
      of CAG140 mice. RESULTS: KI mice fed a curcumin-containing diet since conception
      showed decreased huntingtin aggregates and increased striatal DARPP-32 and D1
      receptor mRNAs, as well as an amelioration of rearing deficits. However, similar
      to other antioxidants, curcumin impaired rotarod behavior in both WT and KI mice
      and climbing in WT mice. These behavioral effects were also noted in WT C57Bl/6 J
      mice exposed to the same curcumin regime as adults. However, neither locomotor
      function, behavioral despair, muscle strength or food utilization were affected
      by curcumin in this latter study. The clinical significance of curcumin's
      impairment of motor performance in mice remains unclear because curcumin has an
      excellent blood chemistry and adverse event safety profile, even in the elderly
      and in patients with Alzheimer's disease. CONCLUSION: Together with this clinical
      experience, the improvement in several transgene-dependent parameters by curcumin
      in our study supports a net beneficial effect of dietary curcumin in HD.

PMID- 22475212
TI  - A relativistic study of the electronic and magnetic properties of cerocene and
      thorocene and its anions.
AB  - In this study, we evaluated the importance of the relativistic effects on the
      optical and magnetic properties of cerocene and thorocene and its corresponding
      anions. The optimized molecular structures show D(8h) symmetry for all systems,
      in good agreement with the experimental data. Atomic charges were analyzed using
      different approaches (Mulliken, AIM, multipole, and NBO), and the results suggest
      that the net charge on the thorium is greater than on the cerium atom; however,
      none of the methodologies were able to predict the expected net charge Ce(III)
      and Th(IV) atoms. However, by an energy decomposition analysis, a significant
      electrostatic, ionic, interaction, ~58% and ~61%, was found between the metal and
      the COT(2-) rings, respectively. The calculated electronic excitations are
      underestimated in comparison with the experimental data, while the calculated EPR
      g-tensors are in agreement with previous theoretical and experimental data.
      Besides, the NICS analysis shows an increased ring electron delocalization due to
      the lanthanide and actinide metals.

PMID- 22475213
TI  - An acquired factor VIII inhibitor in a myeloproliferative neoplasm presenting
      with severe retroperitoneal hemorrhage.

PMID- 22475214
TI  - Extremely strong self-assembly of a bimetallic salen complex visualized at the
      single-molecule level.
AB  - A bis-Zn(salphen) structure shows extremely strong self-assembly both in solution
      as well as at the solid-liquid interface as evidenced by scanning tunneling
      microscopy, competitive UV-vis and fluorescence titrations, dynamic light
      scattering, and transmission electron microscopy. Density functional theory
      analysis on the Zn(2) complex rationalizes the very high stability of the self
      assembled structures provoked by unusual oligomeric (Zn-O)(n) coordination motifs
      within the assembly. This coordination mode is strikingly different when compared
      with mononuclear Zn(salphen) analogues that form dimeric structures having a
      typical Zn(2)O(2) central unit. The high stability of the multinuclear structure
      therefore holds great promise for the development of stable self-assembled
      monolayers with potential for new opto-electronic materials.

PMID- 22475215
TI  - Association of interleukin-6 and interleukin-8 with poor prognosis in elderly
      patients with chronic lymphocytic leukemia.
AB  - In population studies, the relative survival in chronic lymphocytic leukemia
      (CLL) decreases with age. In this study, we demonstrated in a cohort of 189
      patients from a CLL clinic that overall survival was lower in the sub-cohort of
      patients aged >= 70 years, but causes of death were similar for all age groups,
      being progressive CLL, secondary malignancies and infections. As normal
      individuals age, the plasma levels of inflammatory cytokines, such as interleukin
      6 (IL-6) and IL-8, can increase. In our patients with CLL, IL-6, IL-8 and tumor
      necrosis factor-alpha (TNF-alpha) levels increased with age to a greater degree
      than in normal individuals, and the levels correlated closely with plasma beta(2)
      microglobulin and with one another. In addition, in patients >= 70 years, IL-6
      was found to be a better prognostic marker than immunoglobulin variable heavy
      chain gene (IgV(H)) status. In vitro studies demonstrated that IL-6 and IL-8
      could enhance the binding of CLL cells to stromal cells, suggesting that their
      clinical activity may be mediated through their effects on the microenvironment.
      Thus, plasma IL-6 is an important prognostic marker for the elderly with CLL, and
      this study highlights that the utility of prognostic markers may depend on
      patient age.

PMID- 22475216
TI  - New structure-activity relationships of A- and D-ring modified steroidal
      aromatase inhibitors: design, synthesis, and biochemical evaluation.
AB  - A- and D-ring androstenedione derivatives were synthesized and tested for their
      abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were
      studied leading to a very active compound, when the C-3 hydroxyl group assumes
      3beta stereochemistry (1, IC(50) = 0.18 MUM). In a second series, the influence
      of double bonds or epoxide functions in different positions along the A-ring was
      studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC(50) =
      0.145 MUM) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3
      carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC(50) =
      0.135 MUM) revealed the best activity, pointing out the importance of planarity
      in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives
      were also studied showing that bulky substituents in C-4 diminish the activity.
      In addition, IFD simulations helped to explain the recognition of the C-3
      hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.

PMID- 22475217
TI  - An analysis of asthma hospitalizations, air pollution, and weather conditions in
      Los Angeles County, California.
AB  - There is now a large body of literature supporting a linkage between exposure to
      air pollutants and asthma morbidity. However, the extent and significance of this
      relationship varies considerably between pollutants, location, scale of analysis,
      and analysis methods. Our primary goal is to evaluate the relationship between
      asthma hospitalizations, levels of ambient air pollution, and weather conditions
      in Los Angeles (LA) County, California, an area with a historical record of heavy
      air pollution. County-wide measures of carbon monoxide (CO), nitrogen dioxide
      (NO(2)), ozone (O(3)), particulate matter<10 MUm (PM(10)), particulate matter<2.5
      MUm (PM(2.5)), maximum temperature, and relative humidity were collected for all
      months from 2001 to 2008. We then related these variables to monthly asthma
      hospitalization rates using Bayesian regression models with temporal random
      effects. We evaluated model performance using a goodness of fit criterion and
      predictive ability. Asthma hospitalization rates in LA County decreased between
      2001 and 2008. Traffic-related pollutants, CO and NO(2), were significant and
      positively correlated with asthma hospitalizations. PM(2.5) also had a positive,
      significant association with asthma hospitalizations. PM(10), relative humidity,
      and maximum temperature produced mixed results, whereas O(3) was non-significant
      in all models. Inclusion of temporal random effects satisfies statistical model
      assumptions, improves model fit, and yields increased predictive accuracy and
      precision compared to their non-temporal counterparts. Generally, pollution
      levels and asthma hospitalizations decreased during the 9 year study period. Our
      findings also indicate that after accounting for seasonality in the data, asthma
      hospitalization rate has a significant positive relationship with ambient levels
      of CO, NO(2), and PM(2.5).

PMID- 22475218
TI  - Reconstructing the life-time lead exposure in children using dentine in deciduous
      teeth.
AB  - Data are presented to demonstrate that the circumpulpal dentine of deciduous
      teeth can be used to reconstruct a detailed record of childhood exposure to lead.
      By combining high spatial resolution laser ablation ICP-MS with dental histology,
      information was acquired on the concentration of lead in dentine from in utero to
      several years after birth, using a true time template of dentine growth. Time
      corrected lead analyses for pairs of deciduous molars confirmed that between
      tooth variation for the same child was negligible and that meaningful exposure
      histories can be obtained from a single, multi-point ablation transect on
      longitudinal sections of individual teeth. For a laser beam of 100 MUm diameter,
      the lead signal for each ablation point represented a time span of 42 days.
      Simultaneous analyses for Sr, Zn and Mg suggest that the incorporation of Pb into
      dentine (carbonated apatite) is most likely controlled by nanocrystal growth
      mechanisms. The study also highlights the importance of discriminating between
      primary and secondary dentine and the dangers of translating lead analyses into
      blood lead estimates without determining the age or duration of dentine sampled.
      Further work is in progress to validate deciduous teeth as blood lead biomarkers.

PMID- 22475219
TI  - Multi-criteria decision analyses. Viewing MCDA in terms of both process and
      aggregation methods: some thoughts, motivated by the paper of Huang, Keisler and
      Linkov.
AB  - The paper of Huang, Keisler and Linkov (HKL) (Huang et al., 2011) has motivated
      us to this note about the relation between ranking procedures and Multi-Criteria
      Decision Analysis (MCDA) tools. The key concept in the HKL-paper is in our eyes
      the 'trade-off'. A 'trade-off' seems necessary, when conflicting indicator values
      are present. HKL stress that the general application of MCDA is hampered by
      different terminology. We do not claim to have a solution for that problem.
      Nevertheless, we think that the discussion is worthwhile and this note presents
      some of our ideas, which basically imply the need of a broadening of the
      definition of MCDA.

PMID- 22475220
TI  - Poplar clones of different sizes, grown on a heavy metal polluted site, are
      associated with microbial populations of varying composition.
AB  - We performed a field trial to evaluate the response of different poplar clones to
      heavy metals. We found that poplar plants of the same clone, propagated by
      cuttings, had a marked variability of survival and growth in different zones of
      the field that were characterized by very similar physical-chemical prosperities.
      Since metal uptake and its accumulation by plants can be affected by soil
      microorganisms, we investigated soil microbial populations that were collected in
      proximity to the roots of large and small poplar plants. We used microbiological
      and molecular tools to ascertain whether bacterial strains or species were
      associated with large, or small poplars, and whether these were different from
      those present in the bulk (without plants) soil. We found that the culturable
      fraction of the bacteria differed in the three cases (bulk soil, small or large
      poplars). While some taxa were always present, two species (Chryseobacterium
      soldanellicola and Variovorax paradoxus) were only found in the soil where
      poplars (large or small) were growing, independently from the plant size.
      Bacterial strains of the genus Flavobacterium were prevalent in the soil with
      large poplar plants. The existence of different microbial populations in the bulk
      and in the poplar grown soils was confirmed by the DGGE profiles of the bacterial
      culturable fractions. Cluster analysis of the DGGE profiles highlighted the clear
      separation of the culturable fraction from the whole microbial community. The
      isolation and identification of poplar-associated bacterial strains from the
      culturable fraction of the microbial community provided the basis for further
      studies aimed at the combined use of plants and soil microorganisms in the
      remediation of heavy metal polluted soils.

PMID- 22475222
TI  - The high frequency of HIV type 1-specific cellular immune responses in
      seronegative individuals with parenteral and/or heterosexual HIV type 1 exposure.
AB  - Some individuals remain HIV seronegative despite repeated unprotected exposure to
      the virus. Recent observations led to a concept that acquired immunity plays a
      role in protection or at least in altered susceptibility to HIV-1 infection in
      highly exposed seronegative (ESN) individuals. Our aim was to study HIV-specific
      cellular immune responses induced in parenterally and/or heterosexually ESN
      individuals. Nine seronegative injection drug users (IDUs), 10 seronegative
      individuals, and nine of their HIV-positive sexual and/or IDU partners from the
      cohort of IDUs were included in the study. The discordant couples had unprotected
      sex, and some of seronegative partners also had parenteral exposure. Cell
      mediated responses were measured in peripheral blood mononuclear cells (PBMCs) by
      ex vivo interferon (IFN)-gamma-ELISpot and ICS combining IFN-gamma, tumor
      necrosis factor (TNF)-alpha, and interleukin (IL)-2 after stimulation with four
      consensus peptide pools (Nef, Gag, RT, Env, subtype A-EE). Thirteen out of 19
      (68%) seronegative study subjects had strong Nef peptide pool-specific ELISpot
      responses, three (16%) subjects responded against the Gag peptide pool, and one
      subject had an RT peptide pool response. Nef peptide pool responses in ESN were
      as high as in seropositive subjects. The multiple HIV-specific cytokine
      production in both CD4(+) and CD8(+) T cells was shown for several ESN subjects.
      The functional profiles of the immune responses were different between
      seronegative and HIV-positive study groups. Whether the observed cellular
      responses have any protective role against HIV needs to be further investigated.

PMID- 22475221
TI  - Microsecond folding dynamics of apomyoglobin at acidic pH.
AB  - Apomyolgobin (apoMb) is an important model for understanding the folding
      mechanism of helical proteins. This study focuses on a partially structured state
      of sperm whale apoMb populated at pH 4.2 (M-state), which structurally resembles
      a late kinetic intermediate in the formation of the native state (N) at higher
      pH. The thermodynamics and cooperativity of apoMb folding at pH 4.2 and 6.2 were
      studied by global analysis of the urea-induced unfolding transitions monitored by
      tryptophan fluorescence and circular dichroism. The kinetics of folding and
      unfolding of apoMb at pH 4.2 was measured over a time window from 40 to 850 MUs,
      using fluorescence-detected continuous-flow measurements. Our observation of
      biphasic kinetics provides clear evidence for rapid (<100 MUs) accumulation of
      previously unresolved intermediate states in both refolding and unfolding
      experiments. Quantitative kinetic modeling of the results, using a four-state
      mechanism with two intermediates on a direct route between the unfolded and
      folded states (U<->I<->L<->M), gave new insight into the conformational states
      and barriers that precede the rate-limiting step in the formation of the N-state
      of apoMb.

PMID- 22475223
TI  - Modeling of activity landscapes for drug discovery.
AB  - INTRODUCTION: Activity landscapes (ALs) are graphical representations that
      integrate compound structure and potency relationships. These computer-generated
      models enable the interactive large-scale analysis of structure-activity
      relationships (SARs) and complement traditional approaches to study SARs of
      individual compound series in a qualitative or quantitative manner. A variety of
      AL designs have been reported. AREAS COVERED: The concept of activity landscapes
      is introduced and different methodologies to represent 2D or 3D AL
      representations of large compound data sets are described on the basis of
      original literature references. Several AL variants and extensions have been
      generated for special applications in medicinal chemistry. These include, for
      example, AL views of evolving data sets with constant topology, selectivity
      landscapes and multi-target ALs, or molecular mechanism and multi-property maps.
      Furthermore, the applicability domain of the AL concept is discussed including
      specific requirements for practical utility in medicinal chemistry opportunities
      for further developments. EXPERT OPINION: AL modeling has substantially extended
      conventional ways to study SARs. The AL concept is inseparable from the notion of
      activity cliffs that are of high interest in SAR analysis. AL design is an area
      of active research at the interface between chemoinformatics and medicinal
      chemistry with potential for further growth. Special emphasis must be put on
      increasing the usability of AL models for practicing medicinal chemists.

PMID- 22475224
TI  - Welcome to the '100% club'!

PMID- 22475225
TI  - Evaluation of three simple direct or indirect carbonyl detection methods for
      characterization of oxidative modifications of proteins.
AB  - Among disruptions induced by oxidative stress, modifications of proteins,
      particularly irreversible carbonylation, are associated with the development of
      several diseases, including cardiovascular diseases, neurodegenerative diseases,
      and cancer. Carbonylation of proteins can occur directly or indirectly through
      the adduction of lipid oxidation products. In this study, three classical and
      easy-to-perform techniques to detect direct or indirect carbonylation of proteins
      were compared. A model protein apomyoglobin and a complex mixture of rat liver
      cytosolic proteins were exposed to cumene hydroperoxide oxidation or adduction to
      the lipid peroxidation product 4-hydroxynonenal in order to test direct or
      indirect carbonylation, respectively. The technique using a specific anti-4
      hydroxynonenal-histidine adduct antibody was effective to detect in vitro
      modification of model apomyoglobin and cytosolic proteins by 4-hydroxynonenal but
      not by direct carbonylation which was achieved by techniques using biotin-coupled
      hydrazide or dinitrophenylhydrazine derivatization of carbonyls. Sequential use
      of these methods enabled the detection of both direct and indirect carbonyl
      modification in proteins, although constitutively biotinylated proteins were
      detected by biotin-hydrazide. Although rather classical and efficient, methods
      for carbonyl detection on proteins in oxidative stress studies may be biased by
      some artifactual detections and complicated by proteins multimerizations. The use
      of more and more specific available antibodies is recommended to complete
      detection of lipid peroxidation product adducts on proteins.

PMID- 22475226
TI  - Synthesis of acyltrifluoroborates.
AB  - Acylboranes are among the most elusive boron-containing organic functional
      groups, a fact that has impeded development of new reactions employing them as
      substrates. A new synthesis of acyltrifluoroborates from benzotriazole (Bt)-based
      N,O-acetals has been developed. Two other routes provide acyltrifluoroborates
      containing alcohols, aldehydes, and carbamates. The ketone-like reactivity of the
      acyltrifluoroborate functional group is demonstrated, and the first X-ray
      structure of an acyltrifluoroborate is reported.

PMID- 22475228
TI  - Embracing nontraditional learning: desperately seeking critical skills.

PMID- 22475227
TI  - Therapeutic implications of an enriched cancer stem-like cell population in a
      human osteosarcoma cell line.
AB  - BACKGROUND: Osteosarcoma is a bone-forming tumor of mesenchymal origin that
      presents a clinical pattern that is consistent with the cancer stem cell model.
      Cells with stem-like properties (CSCs) have been identified in several tumors and
      hypothesized as the responsible for the relative resistance to therapy and tumor
      relapses. In this study, we aimed to identify and characterize CSCs populations
      in a human osteosarcoma cell line and to explore their role in the responsiveness
      to conventional therapies. METHODS: CSCs were isolated from the human MNNG/HOS
      cell line using the sphere formation assay and characterized in terms of self
      renewal, mesenchymal stem cell properties, expression of pluripotency markers and
      ABC transporters, metabolic activity and tumorigenicity. Cell's sensitivity to
      conventional chemotherapeutic agents and to irradiation was analyzed and related
      with cell cycle-induced alterations and apoptosis. RESULTS: The isolated CSCs
      were found to possess self-renewal and multipotential differentiation
      capabilities, express markers of pluripotent embryonic stem cells Oct4 and Nanog
      and the ABC transporters P-glycoprotein and BCRP, exhibit low metabolic activity
      and induce tumors in athymic mice. Compared with parental MNNG/HOS cells, CSCs
      were relatively more resistant to both chemotherapy and irradiation. None of the
      treatments have induced significant cell-cycle alterations and apoptosis in CSCs.
      CONCLUSIONS: MNNG/HOS osteosarcoma cells contain a stem-like cell population
      relatively resistant to conventional chemotherapeutic agents and irradiation.
      This resistant phenotype appears to be related with some stem features, namely
      the high expression of the drug efflux transporters P-glycoprotein and BCRP and
      their quiescent nature, which may provide a biological basis for resistance to
      therapy and recurrence commonly observed in osteosarcoma.

PMID- 22475229
TI  - Using the Transtheoretical Model for outcome evaluation in continuing education.
AB  - Measuring the outcomes of continuing education programs can be challenging for
      providers. One method to measure change behavior is to measure learners'
      readiness to act using the Transtheoretical Model. Outcomes for this evaluation
      method can also assist providers in planning future education programs designed
      to meet learners' needs in their stage of behavior change.

PMID- 22475230
TI  - Launching care partners in medical-surgical nursing.
AB  - In the wake of health care reform, a large health system developed a new model of
      medical-surgical nursing care delivery. To facilitate the subsequent culture
      change, a non-traditional educational approach was used to provide a dynamic
      experiential venue that included real-time feedback to facilitate nurses'
      behavioral transformation.

PMID- 22475231
TI  - Meaningful use of Web 2.0 tools for teaching and learning.
AB  - Given the ever-increasing set of online learning tools that are easily accessible
      through mobile devices, nurse educators can choose from a range of free and low
      cost applications to promote active and engaged learning. This column offers
      several "tips" for using these tools.

PMID- 22475233
TI  - Multilocus sequence typing (MLST) analysis of 104 Clostridium difficile strains
      isolated from China.
AB  - The phylogenetic and epidemic relationships of 104 clinical isolates of
      Clostridium difficile from three hospitals of different geographical and
      population sources in China were investigated by multilocus sequence typing.
      Twenty-two sequence types (STs) were identified, four of which, ST117, ST118,
      ST119 and ST129, were novel. No geographically specific and host population
      specific phylogenetic lineages were found and there was no correlation between
      geographical origin or host population and strain genotype. ST37 was the dominant
      type in our survey but the four novel STs underline the high genetic diversity
      and unique polymorphisms in C. difficile from China.

PMID- 22475234
TI  - [A vomiting neonate].
AB  - A 24-days-old male neonate presented with vomiting directly after feeding.
      Physical examination showed a prominent peristaltic wave, indicating an
      obstruction of the pylorus. This diagnosis was confirmed with a capillary
      bloodgas measurement and ultrasound examination. A Ramstedt procedure was
      performed without complications.

PMID- 22475236
TI  - [Lucio's phenomenon in a patient with leprosy on Aruba].
AB  - BACKGROUND: Lucio's phenomenon is a rare leprosy reaction characterised by
      bizarrely-shaped, purpuric skin lesions and ulceration. It occurs in diffuse
      lepromatous leprosy and it is mainly reported in patients from Mexico and the
      Caribbean. CASE DESCRIPTION: We describe the case of a 90-year-old Aruban man
      with recurrent leg ulcers and flexion contractures of the lower extremities.
      Occurrence of Lucio's phenomenon led to a diagnosis of diffuse lepromatous
      leprosy. Presence of Mycobacterium leprae was demonstrated in skin, bone marrow
      and lymph nodes. CONCLUSION: Lucio's phenomenon led to a diagnosis of leprosy.
      Leprosy is still endemic in Aruba.

PMID- 22475238
TI  - [Metamizole in postoperative pain management].
AB  - Postoperative pain management is an essential part of surgical management. In the
      Netherlands paracetamol, NSAIDs and, if necessary, opioids are the most commonly
      used drugs for perioperative analgesia. Metamizole is a non-opioid analgesic that
      is rarely used in the Netherlands, although it is one of the most frequently used
      analgesics around the world. Metamizole is registered in the Netherlands for
      intravenous therapy for acute pain. However, the drug has been rarely used since
      the 1970s because of what was thought to be an unacceptable risk of
      agranulocytosis. Recent scientific data do not justify this reasoning. Its
      mechanism of action is still under discussion, but the main action is likely to
      be an inhibition of prostaglandin synthesis in both peripheral tissues and the
      central nervous system. Based on the current literature, metamizole deserves a
      role in the management of post-operative pain in the Netherlands. It seems to be
      a safe and effective drug for acute pain management especially when compared with
      NSAIDs.

PMID- 22475239
TI  - [Computer-assisted cardiovascular disease management: better implementation of
      care but no improvement in clinical outcomes].
AB  - Computer support is considered by many to be a promising strategy for improving
      healthcare interventions, especially in the management of chronic diseases. So
      far, however, evidence of the effectiveness of ICT support in healthcare is
      limited. Recently, computer-supported cardiovascular disease management was
      compared with usual care during an RCT comprised of 1100 primary care patients.
      This trial demonstrated that neither the clinical outcome nor the cardiovascular
      morbidity rate improved, even though management of the risk factors improved over
      1 year of follow-up. The pragmatic design of the RCT in daily general practice
      may have restricted implementing the computer support, and may also have hampered
      the evaluation of the cardiovascular effects. The results demonstrate that
      although computer support may help improve the performance of disease management,
      its impact on disease outcomes is questionable. ICT innovations in healthcare
      require rigorous investigative evaluation before their implementation in daily
      practice can be justified.

PMID- 22475240
TI  - [Pelvic injuries caused by bucking horses].
AB  - We report on 3 male patients aged 57, 47, and 53, who each sustained an unstable
      straddle injury during low-energy pelvic trauma while horseback riding. All 3
      patients were haemodynamically stable; radiography revealed diastasis of the
      pubic symphysis in each case. In two patients, the sacroiliac joints were intact
      but the third patient showed widening of the right sacroiliac joint. In this
      patient, the pelvis was initially fixated with osteosynthesis screws and dynamic
      compression plates; however, arthrodesis of the right sacroiliac joint was
      performed due to its non-union one year after the injury. Fractures of the pelvic
      ring are relatively rare and are typically associated with high-energy trauma.
      Immediate surgical treatment is necessary for patients with fractures of the
      pelvic ring for the stabilisation of haemorrhagic shock, identification of soft
      tissue injuries and fixation of the pelvis.

PMID- 22475241
TI  - Comparative effects of surgical and percutaneous repair on P-wave and
      atrioventricular conduction in patients with atrial septal defect--ostium
      secundum type.
AB  - Both surgical and percutaneous closures of atrial septal defects have been
      successful in reversal of atrial dilatation. We compared the effects of surgical
      and percutaneous transvenous device closure of atrial septal defect on post
      operative changes of P-wave duration, PR segment, and PR interval.
      Electrocardiographic data were prospectively collected from 30 patients following
      either surgical (n equal to 16) or percutaneous (n equal to 16) repair of atrial
      septal defects between 2004 and 2010. A cardiologist blinded to the closure
      technique performed the electrocardiographic analyses. P-wave duration (98.5 plus
      or minus 15.4 to 86.4 plus or minus 13.2 milliseconds, p-value less than 0.05)
      and PR interval (162.9 plus or minus 18.5 to 140.6 plus or minus 15.2
      milliseconds, p-value less than 0.05) were reduced after percutaneous transvenous
      device closure. P-wave duration (104.5 plus or minus 24.7 versus 83.2 plus or
      minus 13.3 milliseconds, p-value less than 0.05) and PR interval (173.2 plus or
      minus 38.7 versus 144.3 plus or minus 32.0 milliseconds, p-value less than 0.05)
      were also reduced after surgical closure. PR segment in the percutaneous group
      was significantly reduced (63.4 plus or minus 14.5 to 52.1 plus or minus 10.8
      milliseconds, p-value less than 0.05), but not in the surgical group (68.6 plus
      or minus 18.7 versus 61.1 plus or minus 24.7 milliseconds). However, the
      difference in PR segment changes between the two groups was not significant (
      11.3 plus or minus 15.0 versus -7.6 plus or minus 20.5 milliseconds, p-value
      equal to 0.18). Our analysis demonstrates that the changes between the two groups
      were not different and that both closure techniques reduce P-wave duration, PR
      segment, and PR interval within 6 months.

PMID- 22475243
TI  - Assessment of 285 cases of chronic lymphocytic leukemia seen at single large
      tertiary center in Northern India.
AB  - Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative
      disorder in the West accounting for about 30% of leukemias, but about 2-4% in
      India. There is no large series reported from India, and hence we decided to
      undertake this study. We assessed the clinicohematological profiles and treatment
      outcomes in 285 patients seen over 11 years at our center (median age 59 years,
      209 males). Sixty-three patients (22%) were asymptomatic and diagnosed
      incidentally. The median total leukocyte count at presentation was 50 * 10(9)/L.
      Rai stage distribution was: stage 0, 10%; stage I, 16%; stage II, 33%; stage III,
      20%; and stage IV, 21%. Fifty percent of patients required treatment at
      presentation. Ninety-six patients received chlorambucil-based (overall response
      rate [ORR] 69%, complete remission [CR] 3%) and 27 patients received fludarabine
      based (ORR 89%, CR 44%) chemotherapy. With a median follow-up of 2.9 years, the
      median overall survival (OS) and event-free survival (EFS) were 5.1 and 4.6
      years, respectively. Fludarabine was more toxic, as half of the patients
      developed febrile neutropenia and various infections. The majority of patients
      presented with advanced stage disease. Fludarabine was less commonly used as
      first-line therapy. Advanced clinical stage (Rai III and IV) was associated with
      poor OS (hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.19-5.11, p =
      0.001) and EFS.

PMID- 22475242
TI  - A cohort study of the recovery of health and wellbeing following colorectal
      cancer (CREW study): protocol paper.
AB  - BACKGROUND: The number of people surviving colorectal cancer has doubled in
      recent years. While much of the literature suggests that most people return to
      near pre-diagnosis status following surgery for colorectal cancer, this
      literature has largely focused on physical side effects. Longitudinal studies in
      colorectal cancer have either been small scale or taken a narrow focus on
      recovery after surgery. There is a need for a comprehensive, long-term study
      exploring all aspects of health and wellbeing in colorectal cancer patients. The
      aim of this study is to establish the natural history of health and wellbeing in
      people who have been treated for colorectal cancer. People have different
      dispositions, supports and resources, likely resulting in individual differences
      in restoration of health and wellbeing. The protocol described in this paper is
      of a study which will identify who is most at risk of problems, assess how
      quickly people return to a state of subjective health and wellbeing, and will
      measure factors which influence the course of recovery. METHODS/DESIGN: This is a
      prospective, longitudinal cohort study following 1000 people with colorectal
      cancer over a period of two years, recruiting from 30 NHS cancer treatment
      centres across the UK. Questionnaires will be administered prior to surgery, and
      3, 9, 15 and 24 months after surgery, with the potential to return to this cohort
      to explore on-going issues related to recovery after cancer. DISCUSSION: Outcomes
      will help inform health care providers about what helps or hinders rapid and
      effective recovery from cancer, and identify areas for intervention development
      to aid this process. Once established the cohort can be followed up for longer
      periods and be approached to participate in related projects as appropriate and
      subject to funding.

PMID- 22475244
TI  - Lipo-gamma-AApeptides as a new class of potent and broad-spectrum antimicrobial
      agents.
AB  - There is increasing demand to develop antimicrobial peptides (AMPs) as next
      generation antibiotic agents, as they have the potential to circumvent emerging
      drug resistance against conventional antibiotic treatments. Non-natural
      antimicrobial peptidomimetics are an ideal example of this, as they have
      significant potency and in vivo stability. Here we report for the first time the
      design of lipidated gamma-AApeptides as antimicrobial agents. These lipo-gamma
      AApeptides show potent broad-spectrum activities against fungi and a series of
      Gram-positive and Gram-negative bacteria, including clinically relevant pathogens
      that are resistant to most antibiotics. We have analyzed their structure-function
      relationship and antimicrobial mechanisms using membrane depolarization and
      fluorescent microscopy assays. Introduction of unsaturated lipid chain
      significantly decreases hemolytic activity and thereby increases the selectivity.
      Furthermore, a representative lipo-gamma-AApeptide did not induce drug resistance
      in S. aureus, even after 17 rounds of passaging. These results suggest that the
      lipo-gamma-AApeptides have bactericidal mechanisms analogous to those of AMPs and
      have strong potential as a new class of novel antibiotic therapeutics.

PMID- 22475245
TI  - The effect of tumor necrosis factor-alpha antagonists on arterial stiffness in
      rheumatoid arthritis: a literature review.
AB  - BACKGROUND: There is evidence that patients with rheumatoid arthritis (RA) have a
      higher arterial stiffness than their age-matched healthy counterparts and thus
      have a higher cardiovascular risk. Under National Institute for Clinical
      Excellence guidelines, tumor necrosis factor-alpha (TNF-alpha) antagonists are
      indicated clinically in patients with severe active rheumatoid disease. TNF-alpha
      antagonists have been found to reduce inflammatory markers in RA; however, it is
      debatable if they have favorable effects on the cardiovascular system. This
      review evaluates the effect of TNF-alpha antagonists on arterial stiffness, a
      predictor of cardiovascular disease, in RA patients. SEARCH STRATEGY: A search of
      Ovid MEDLINE and ISI Web of Knowledge databases was conducted to identify studies
      into the effect of TNF-alpha antagonists on arterial stiffness in RA patients.
      Eight studies matching the search criteria were included for analysis. FINDINGS:
      Two methods were used to assess arterial stiffness: pulse wave velocity and
      augmentation index. Despite inconsistencies in augmentation index values, aortic
      pulse wave velocity in all but one study was significantly reduced following TNF
      alpha antagonist treatment. Most studies had methodological limitations,
      including inadequate sample size, nonblinding of those involved in the
      measurements, and inadequate inclusion/exclusion criteria. Variation in results
      could be due to the use of different TNF-alpha antagonists, different outcome
      measures being used, and differences in follow-up. CONCLUSIONS: The balance of
      evidence suggests that TNF-alpha antagonists may have a beneficial effect on
      arterial stiffness and therefore cardiovascular risk. However, larger more robust
      longer term studies are warranted to confirm recent findings.

PMID- 22475246
TI  - Rheumatoid arthritis is an independent risk factor for an increased augmentation
      index regardless of the coexistence of traditional cardiovascular risk factors.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with increased cardiovascular
      morbidity. It was previously shown that the augmentation index (AIx), a marker of
      vascular dysfunction, is higher in RA patients without traditional cardiovascular
      risk factors than in healthy controls. In this study we determined whether the
      impact of RA on the AIx is diminished in the context of coexisting, strong
      cardiovascular risk factors. PATIENTS AND METHODS: A total of 411 participants
      were included [203 with RA; 208 in the non-RA (n-RA) group]. Pulse-wave analysis
      was performed on the radial artery using applanation tonometry. The impact of RA
      on the AIx was determined in a single and in a multiple linear regression model.
      RESULTS: The mean unadjusted AIx was 30.5 +/- 9.0% for RA patients and 24.0 +/-
      11.0% for the n-RA group (P < 0.001). In the regression model, the following
      variables are statistically significant at approximately the same level (P <
      0.001); the order of impact of these variables is age > diastolic blood pressure
      > sex > RA > height > smoking status. RA, height, and smoking had a nearly equal
      impact on the AIx. CONCLUSIONS: The AIx is increased in RA patients regardless of
      the coexistence of traditional cardiovascular risk factors, thereby reflecting
      vascular dysfunction in this population. The impact of RA on the vascular system
      is comparable to that of smoking.

PMID- 22475247
TI  - Comment on Enhancement of the catalytic activity of a 27 kDa subtilisin-like
      enzyme from Bacillus amyloliquefaciens CH51 by in vitro mutagenesis.

PMID- 22475248
TI  - Celiac disease and diabetes mellitus diagnosed in a pediatric patient with
      Hirschsprung disease.
AB  - Hirschsprung disease is a disorder of neural crest migration characterized by
      intestinal aganglionosis along a variable segment of the gastrointestinal tract.
      It is a complex disorder associated with several syndromes. Celiac disease is an
      autoimmune enteropathy characterized by dietary intolerance to gluten proteins
      and can be associated with autoimmune conditions such as diabetes mellitus.
      Celiac disease can mimic Hirschsprung disease when presenting with constipation
      and abdominal distention. We present the case of celiac disease diagnosed in a
      patient with Hirschsprung disease who subsequently developed type one diabetes
      mellitus.

PMID- 22475250
TI  - Nanoparticles and children's lungs: is there a need for caution?

PMID- 22475249
TI  - Microneedle-mediated vaccine delivery: harnessing cutaneous immunobiology to
      improve efficacy.
AB  - INTRODUCTION: Breaching the skin's stratum corneum barrier raises the possibility
      of the administration of vaccines, gene vectors, antibodies and even
      nanoparticles, all of which have at least their initial effect on populations of
      skin cells. AREAS COVERED: Intradermal vaccine delivery holds enormous potential
      for improved therapeutic outcomes for patients, particularly those in the
      developing world. Various vaccine-delivery strategies have been employed, which
      are discussed in this review. The importance of cutaneous immunobiology on the
      effect produced by microneedle-mediated intradermal vaccination is also
      discussed. EXPERT OPINION: Microneedle-mediated vaccines hold enormous potential
      for patient benefit. However, in order for microneedle vaccine strategies to
      fulfill their potential, the proportion of an immune response that is due to the
      local action of delivered vaccines on skin antigen-presenting cells, and what is
      due to a systemic effect from vaccines reaching the systemic circulation, must be
      determined. Moreover, industry will need to invest significantly in new equipment
      and instrumentation in order to mass-produce microneedle vaccines consistently.
      Finally, microneedles will need to demonstrate consistent dose delivery across
      patient groups and match this to reliable immune responses before they will
      replace tried-and-tested needle-and-syringe-based approaches.

PMID- 22475251
TI  - Deposition of small particles in the developing lung.
AB  - Infancy is a time of marked and rapid changes in respiratory tract development.
      Infants (0-1 year of age) and young children (1- 3 years of age) are a unique
      subpopulation with regard to therapeutic aerosols. Anatomical, physiological and
      emotional factors, peculiar to these age groups, present significant challenges
      for aerosol delivery to the respiratory tract. Most studies with inhaled
      corticosteroids (ICS) have administered aerosols with relatively large particles,
      frequently > 3 MUm in mass median aerodynamic diameter (MMAD). These drugs were
      designed for use in adults and older children and were administered with masks
      which were frequently rejected by children under age 3-4 years. We review the
      reasons that large-particle aerosols are likely to be less effective in infants
      and young children. We suggest that the benefit of inhaled medications in this
      age group requires further evaluation to determine if better therapeutic outcomes
      might be achieved using smaller particles and more patient-friendly delivery
      systems.

PMID- 22475252
TI  - Airborne engineered nanoparticles: potential risks and monitoring challenges for
      assessing their impacts on children.
AB  - Engineered nanoparticles (ENPs) are the building blocks of novel materials and
      consumer products that hold great promise for our societies. When ENPs are
      released to the environment, however, they can induce irreversible processes that
      can affect human health. To ensure safety for all nanoparticle-based products
      throughout their life cycle we urgently need to develop techniques for
      determining their toxic effects and the exposure levels of humans to ENPs. In an
      attempt to estimate whether nanotechnology can threaten more sensitive parts of
      the population such as children, we provide a brief overview of the potential
      pathways of introducing ENPs into the environment and the state-of-the-art
      techniques for assessing human exposure, as well as our current knowledge on
      their toxic effects.

PMID- 22475254
TI  - The occurrence of ultrafine particles in the specific environment of children.
AB  - Interest in ultrafine particles (UFP) has been increasing due to their specific
      physico-chemical characteristics. Ultrafine particles are those with an
      aerodynamic diameter of <0.1 MUm and are also commonly know as nanoparticles (0.1
      MUm = 100 nm). Due to their small size UFP contribute mostly to particle number
      concentrations and are therefore underestimated in actual pollution measurements,
      which commonly measure mass concentration. Children represent the most vulnerable
      group in regard to particulate exposure due to their developing status and
      different exposures compared to adults. This review discusses the sources of
      ultrafine particles as well as the specific exposures of children highlighting
      the importance and uniqueness of this age group.

PMID- 22475253
TI  - Imaging the paediatric lung: what does nanotechnology have to offer?
AB  - This review will provide an overview of current research into lung imaging with
      nanoparticles, with a focus on the use of nanoparticles as molecular imaging
      agents to observe pathological processes and to monitor the effectiveness of
      nanoparticulate drug delivery systems. Various imaging modalities together with
      their advantages and limitations for lung imaging will be discussed. We will also
      explore the range of nanoparticles used, as well as active or passive targeting
      of nanoparticles.

PMID- 22475255
TI  - The developing respiratory tract and its specific needs in regard to ultrafine
      particulate matter exposure.
AB  - Nanoparticles have unique physico-chemical properties compared to larger
      particles that have the potential to provide promising new possibilities for
      biomedical applications. Considerable research is currently exploring these
      potentials of nanotechnology. In contrast, airborne particles as components of
      indoor air, ambient air pollution associated with traffic-related pollution,
      industry, power plants, and other combustion sources have the potential to harm
      children's health. However, a similar research effort into the potential health
      effects of exposure to nanoparticles is lacking. Children differ markedly from
      adults in their developmental biology rendering young children the most
      vulnerable group with regard to potentially harmful effects induced by
      particulate exposure. This review discusses the differences between children and
      adults in regard to nanoparticle exposure highlighting the uniqueness and
      vulnerability of children.

PMID- 22475256
TI  - Management of asthma in children with long QT syndrome.
AB  - The Long QT syndrome (LQTS) is a rare disorder in which patients are prone to
      life threatening ventricular arrhythmia and is a leading cause of sudden death in
      childhood. Asthma is common and its management in those with LQTS presents a
      number of potential difficulties. The mainstay of therapy in LQTS is beta
      blockade, which may worsen symptoms of asthma. Conversely, beta-agonist therapy
      is the mainstay of asthma management; which, in those with LQTS, may provoke
      ventricular arrhythmias. We review available data regarding the management of
      coexistent LQTS and asthma, and provide a summary of the necessary considerations
      in managing these patients.

PMID- 22475257
TI  - Beyond the guidelines: fatal and near-fatal asthma.
AB  - While asthma is extremely common, fatal and near fatal asthma is rare and often
      preventable if there is early recognition of symptom progression and appropriate
      intervention. In the past decade, asthma mortality has progressively declined in
      association with the widespread use of inhaled corticosteroids and asthma care
      plans. Management of life threatening asthma requires patient education to ensure
      the proper use of medications and to enable the patient to recognize when
      additional therapy for poorly controlled asthma is required. There is some
      evidence that suggests that the overly aggressive use of asthma medications when
      treating a severe exacerbation may contribute to morbidity. Because of the risks
      of air trapping and barotrauma associated with partial airway obstruction, it is
      best to avoid mechanical ventilation if possible but when this is used, low tidal
      volumes, longer exhalation times, and permissive hypercarbia can minimize these
      risks. There is the promise that a better understanding of asthma immunology and
      severe asthma "phenotypes" will lead to better prevention and therapy.

PMID- 22475258
TI  - Pulmonary embolism in children.
AB  - Unlike in adults, pulmonary embolism (PE) is an infrequent event in children. It
      has a marked bimodal distribution during the paediatric years, occurring
      predominantly in neonates and adolescents. The most important predisposing
      factors to PE in children are the presence of a central venous line (CVL),
      infection, and congenital heart disease. Clinical signs of PE are non-specific in
      children or can be masked by underlying conditions. Diagnostic testing is
      necessary in children, especially with the lack of clinical prediction rules.
      Recommendations for tests are derived from adult studies with
      ventilation/perfusion (V/Q) scintigraphy being well established. There exists an
      increasing role for computerised tomography pulmonary angiography (CTPA) and
      magnetic resonance pulmonary angiography (MRPA). Thrombotic events in children
      are initially treated with unfractionated heparin (UFH) or low molecular weight
      heparin (LMWH). For the extended anticoagulant therapy LMWH or vitamin K
      antagonists can be used with duration of treatment recommendations extrapolated
      from adult data. Mortality rates for PE in children are reported to be around
      10%, with death usually related to the underlying disease processes. Exact data
      about recurrence risk in children is unknown. Because of the difference in
      aetiology, presentation, diagnostic methods and treatment between adults and
      children further research is necessary to assess the validity of recommendations
      for children.

PMID- 22475259
TI  - Inpatient paediatric rehabilitation in chronic respiratory disorders.
AB  - Inpatient pulmonary rehabilitation programs have evolved from tuberculosis
      sanatoriums to modern medical centres providing standardized comprehensive care
      in a multidiciplinatory environment. Goals of rehabilitation programs for
      children and adolescents include restoration of professional activity,
      improvement of health condition, compliance and disease management as well as
      restoration of quality of life. Eligibility for an intervention is assessed by
      defined social and medical criteria. Comprehensive pulmonary rehabilitation
      programs provide a wide range of health care recourses, including diagnostic
      procedures, specific medical care, educational interventions and a
      multiprofessional team. Paediatric rehabilitation programs for chronic
      respiratory diseases, such as asthma or cystic fibrosis, have been shown to
      reduce symptoms, increase aerobic fitness and physical strength, improve
      pulmonary function and inflammation and enhance compliance, self-management,
      quality of life and psychological symptoms. Regional climatic effects have
      demonstrated an additional positive effect on the rehabilitation outcome. In
      addition, first evidence suggests an overall reduction of health care costs.

PMID- 22475260
TI  - How to get your paper accepted for publication.
AB  - This paper is an attempt to convey in a lucid way how to go about writing a
      scientific article for publication in an appropriate journal. Topics covered are:
      a) reasons to write a paper b) types of papers c) asking a question and
      formulating an hypothesis d) the complex series of steps necessary before you
      begin your study e) additional considerations once your study is complete f) the
      process of writing the paper and g) writing skills. In the concluding remarks I
      comment on the possibility of rejection of your submission which should not be
      taken personally. If this does occur it should not deter you from contributing to
      medical science.

PMID- 22475262
TI  - Simultaneous determination of some antiprotozoal drugs in different combined
      dosage forms by mean centering of ratio spectra and multivariate calibration with
      model updating methods.
AB  - BACKGROUND: Metronidazole (MET) and Diloxanide Furoate (DF), act as antiprotozoal
      drugs, in their ternary mixtures with Mebeverine HCl (MEH), an effective
      antispasmodic drug. This work concerns with the development and validation of two
      simple, specific and cost effective methods mainly for simultaneous determination
      of the proposed ternary mixture. In addition, the developed multivariate
      calibration model has been updated to determine Metronidazole benzoate (METB) in
      its binary mixture with DF in Dimetrol(r) suspension. RESULTS: Method (I) is the
      mean centering of ratio spectra spectrophotometric method (MCR) that depends on
      using the mean centered ratio spectra in two successive steps that eliminates the
      derivative steps and therefore the signal to noise ratio is enhanced. The
      developed MCR method has been successfully applied for determination of MET, DF
      and MEH in different laboratory prepared mixtures and in tablets. Method (II) is
      the partial least square (PLS) multivariate calibration method that has been
      optimized for determination of MET, DF and MEH in Dimetrol (r) tablets and by
      updating the developed model, it has been successfully used for prediction of
      binary mixtures of DF and Metronidazole Benzoate ester (METB) in Dimetrol (r)
      suspension with good accuracy and precision without reconstruction of the
      calibration set. CONCLUSION: The developed methods have been validated; accuracy,
      precision and specificity were found to be within the acceptable limits. Moreover
      results obtained by the suggested methods showed no significant difference when
      compared with those obtained by reported methods. GRAPHICAL

PMID- 22475261
TI  - Mucin biopolymers as broad-spectrum antiviral agents.
AB  - Mucus is a porous biopolymer matrix that coats all wet epithelia in the human
      body and serves as the first line of defense against many pathogenic bacteria and
      viruses. However, under certain conditions viruses are able to penetrate this
      infection barrier, which compromises the protective function of native mucus.
      Here, we find that isolated porcine gastric mucin polymers, key structural
      components of native mucus, can protect an underlying cell layer from infection
      by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus
      (MCV), or a strain of influenza A virus. Single particle analysis of virus
      mobility inside the mucin barrier reveals that this shielding effect is in part
      based on a retardation of virus diffusion inside the biopolymer matrix. Our
      findings suggest that purified mucins may be used as a broad-range antiviral
      supplement to personal hygiene products, baby formula or lubricants to support
      our immune system.

PMID- 22475264
TI  - A five-factor measure of dependent personality traits.
AB  - This study provides convergent, discriminant, and incremental validity data for a
      new measure of dependent personality traits from the perspective of the five
      factor model (FFM). Dependent personality trait scales were constructed as
      maladaptive variants of FFM facets (e.g., Gullibility as a maladaptive variant of
      FFM trust). Based on responses from 383 undergraduates, the convergent validity
      of the Five-Factor Dependency Inventory (FFDI) scales was tested with respect to
      2 measures of the FFM, 6 dependency trait scales, and 4 measures of dependent
      personality disorder. Discriminant validity was tested with respect to FFM facets
      from alternative domains. Incremental validity was tested with respect to the
      ability of the FFM dependent personality trait scales to account for variance in
      2 established measures of dependency, after variance accounted for by respective
      FFM facet scales and other measures of DPD was first removed. The results of this
      study provided support for the validity of the FFDI assessment of dependency from
      the perspective of the FFM.

PMID- 22475263
TI  - Stereoselective assembly of complex oligosaccharides using anomeric sulfonium
      ions as glycosyl donors.
AB  - The development of selectively protected monosaccharide building blocks that can
      reliably be glycosylated with a wide variety of acceptors is expected to make
      oligosaccharide synthesis a more routine operation. In particular, there is an
      urgent need for the development of modular building blocks that can readily be
      converted into glycosyl donors for glycosylations that give reliably high 1,2-cis
      anomeric selectivity. We report here that 1,2-oxathiane ethers are stable under
      acidic, basic, and reductive conditions making it possible to conduct a wide
      range of protecting group manipulations and install selectively removable
      protecting groups such as levulinoyl (Lev) ester, fluorenylmethyloxy (Fmoc)- and
      allyloxy (Alloc)-carbonates, and 2-methyl naphthyl ethers (Nap). The 1,2
      oxathiane ethers could easily be converted into bicyclic anomeric sulfonium ions
      by oxidization to sulfoxides and arylated with 1,3,5-trimethoxybenzene. The
      resulting sulfonium ions gave high 1,2-cis-anomeric selectivity when glycosylated
      with a wide variety of glycosyl acceptors including properly protected amino
      acids, primary and secondary sugar alcohols and partially protected
      thioglycosides. The selective protected 1,2-oxathianes were successfully employed
      in the preparation of a branched glucoside derived from a glycogen-like
      polysaccharide isolated form the fungus Pseudallescheria boydii , which is
      involved in fungal phagocytosis and activation of innate immune responses. The
      compound was assembled by a latent-active glycosylation strategy in which an
      oxathiane was employed as an acceptor in a glycosylation with a sulfoxide donor.
      The product of such a glycosylation was oxidized to a sulfoxide for a subsequent
      glycosylation. The use of Nap and Fmoc as temporary protecting groups made it
      possible to install branching points.

PMID- 22475265
TI  - De-risking bio-therapeutics for possible drug interactions using cryopreserved
      human hepatocytes.
AB  - Inflammatory diseases such as rheumatoid arthritis and psoriasis are
      characterized by increases in circulating cytokines, which play an important role
      in modulation of the disease state. Several marketed bio-therapeutics target
      cytokines and act as effective treatment strategies. Previous in-vitro and in
      vivo studies have suggested that cytokines may have both direct and indirect
      effects on drug metabolizing enzyme levels in the liver. Few studies have
      characterized models to evaluate the risk of potential drug interactions that
      might be mediated by changes in cytokine levels. In the present studies the
      potential of three cytokines (IL-2, IL-6 and TNF-alpha) to modulate gene
      expression and activity of the major human cytochrome P450 (CYP) enzymes (CYP1A2,
      2B6, 2C9, 2C19, 2D6, and 3A4) in cryopreserved human hepatocytes (CHH) was
      investigated. Significant decreases in the activity of all 6 CYP isoforms
      occurred in hepatocytes incubated with TNF-alpha or IL-6 (17-85%; and 22-76% of
      untreated control values, respectively). TNF-alpha down-regulated the gene
      expression of CYP1A2, 2D6 and 3A4 only, whereas IL-6 down-regulated gene
      expression of all of the tested CYP isoforms except 2D6. IL-2 had only mild
      effects on CYP activity and mRNA levels of examined isoforms. In CHH exposed to
      TNF-alpha, changes in CYP activity were not always paralleled by gene expression
      alterations for three of the examined CYP isoforms. These studies highlight
      several potential pitfalls in using isolated human hepatocytes for determination
      of drug interactions by bio-therapeutics including lack of correlation of mRNA
      and activity measurements for some CYP isoforms when using single time point
      determinations, and appropriateness of the model for indirect acting cytokine and
      cytokine modulators.

PMID- 22475266
TI  - Drug interaction potential of trastuzumab emtansine (T-DM1) combined with
      pertuzumab in patients with HER2-positive metastatic breast cancer.
AB  - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate comprised of
      trastuzumab and the cytotoxic agent DM1 (derivative of maytansine) linked by a
      stable linker N-succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate
      (SMCC). T-DM1 targets an epitope located at subdomain IV of human epidermal
      growth factor receptor 2 (HER2). Pertuzumab is a monoclonal antibody that targets
      an epitope located at subdomain II of HER2, distinct from the epitope recognized
      by T-DM1. The pharmacokinetics (PK), safety, and efficacy of T-DM1 combined with
      pertuzumab were studied in a phase 1b/2 trial in 67 patients with HER2-positive,
      locally advanced or metastatic breast cancer (MBC). The therapeutic protein-drug
      interaction (TP-DI) potential of T-DM1 plus pertuzumab was evaluated. The PK of T
      DM1-related analytes and pertuzumab were compared with historical PK data. The
      results show that the exposure of T-DM1 and DM1, as estimated by noncompartmental
      analyses, was comparable with that reported by historical single-agent studies in
      patients with HER2-positive MBC. T-DM1 clearance and volume of distribution in
      the central compartment, as estimated by population PK analysis, were also
      comparable between this study and historical single-agent studies in patients
      with HER2-positive MBC. Summary statistics of pertuzumab trough and maximal
      exposure (concentrations at predose and 15-30 minutes after the end of infusion
      at cycle 1 and at steady state) were similar with those observed in a
      representative historical single-agent study with the same dosing regimen. The
      visual predictive check plot by population simulation further confirmed that T
      DM1 did not alter pertuzumab PK. Based on these data and the PK and
      pharmacodynamic properties of T-DM1 and pertuzumab, the risk of TP-DI appears to
      be low when T-DM1 and pertuzumab are given together.

PMID- 22475267
TI  - Effects of interleukin 1beta (IL-1beta) and IL-1beta/interleukin 6 (IL-6)
      combinations on drug metabolizing enzymes in human hepatocyte culture.
AB  - Exposure to cytokines can down-regulate hepatic cytochrome P450 enzymes.
      Accordingly, relief of inflammation by cytokinetargeted drug therapy has the
      potential to up-regulate cytochrome P450s and thereby increase clearance of co
      administered drugs. This study examined the effects of the inflammatory cytokine,
      interleukin 1beta (IL-1beta), and IL-1beta/interleukin 6 (IL-6) combinations on
      drug metabolizing enzymes in human hepatocyte culture. Treatment of hepatocytes
      with IL-1beta revealed suppression of mRNA expression of several clinically
      important cytochrome P450 isoenzymes, with EC50 values that differed by
      isoenzyme. Suppression of CYP1A2 activity by IL-1beta could not be measured in 3
      of 5 donors due to lack of response, and in the two remaining donors the average
      EC50 was 450 pg/mL. CYP3A activity had an EC50 of suppression of 416 +/- 454
      pg/mL. Measurable EC50s were obtained for all 5 donors for CYP2C8, 3A4, 3A5, 4A11
      and IL-6R mRNA with fold differences which varied between 9.5-fold (CYP2C8) to
      109-fold (CYP4A11). When hepatocytes were treated with IL-1beta and IL-6 in
      combination at concentrations which ranged from 1-100 pg/mL, IL-6 was the main
      determinant of increases in acute phase response marker mRNA and of decreases in
      CYP3A4 mRNA. There was no synergy between IL-1beta and IL-6 in the regulation of
      cytochrome P450 mRNA when dosed in combination, although the effects of the two
      cytokines in combination were additive in certain instances. These data indicate
      that IL-1beta and IL-6 both suppress cytochrome P450 mRNA and enzyme levels in
      vitro and that, at similar physiologically-relevant concentrations in vitro, IL-6
      is more potent than IL-1beta.

PMID- 22475268
TI  - Editorial: SNPs of drug metabolic enzymes and personalized medicine Part II.

PMID- 22475269
TI  - Catabolic fate and pharmacokinetic characterization of trastuzumab emtansine (T
      DM1): an emphasis on preclinical and clinical catabolism.
AB  - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate in clinical
      development for the treatment of human epidermal growth factor receptor 2 (HER2)
      positive cancers. Herein, we describe a series of studies to assess T-DM1
      absorption, distribution, metabolism, and excretion (ADME) in rats as well as to
      assess human exposure to T-DM1 catabolites. Following administration of unlabeled
      and radiolabeled T-DM1 in female Sprague Dawley rats as a single dose, plasma,
      urine, bile and feces were assessed for mass balance, profiling and
      identification of catabolites. In rats, the major circulating species in plasma
      was T-DM1, while DM1 concentrations were low (1.08 to 15.6 ng/mL). The major
      catabolites found circulating in rat plasma were DM1, [N-maleimidomethyl]
      cyclohexane-1- carboxylate-DM1 (MCC-DM1), and Lysine-MCC-DM1. These catabolites
      identified in rats were also detected in plasma samples from patients with HER2
      positive metastatic breast cancer who received single-agent T-DM1 (3.6 mg/kg
      every 3 weeks) in a phase 2 clinical study. There was no evidence of tissue
      accumulation in rats or catabolite accumulation in human plasma following
      multiple dosing. In rats, T-DM1 was distributed nonspecifically to the organs
      without accumulation. The major pathway of DM1-containing catabolite elimination
      in rats was the fecal/biliary route, with up to 80% of radioactivity recovered in
      the feces and 50% in the bile. The rat T-DM1 ADME profile is likely similar to
      the human profile, although there may be differences since trastuzumab does not
      bind the rat HER2- like receptor. Further research is necessary to more fully
      understand the T-DM1 ADME profile in humans.

PMID- 22475270
TI  - Effects of culture duration on gene expression of P450 isoforms, uptake and
      efflux transporters in primary hepatocytes cultured in the absence and presence
      of interleukin-6: implications for experimental design for the evaluation of
      downregulatory effects of biotherapeutics.
AB  - We report here a comprehensive evaluation of the effects of culture duration on
      the gene expression of P450 isoforms, uptake transporters and efflux transporters
      in human hepatocyte cultured in the absence and presence of the prototypical
      proinflammatory cytokine, interleukin-6 (IL-6). Primary collagen-matrigel
      sandwich cultures of human hepatocytes were cultured in supplemented William's E
      medium containing 0, 0.1, 0.5 and 5 ng/mL of IL-6 for the time periods of 2, 6,
      12, 24 and 48 hrs. Real-time PCR was performed to quantify gene expression of
      acute phase proteins (suppressor of cytokine signaling 3 (SOCS-3), c-reactive
      protein (CRP) and lipopolysaccharide (LPS)-binding proteins (LBP)); P450 isoforms
      (CYPs 1A2, 2B6, 2C8, 2C9, 2D6, 3A4, and 3A5), uptake transporters (SLC10A1,
      SLC22A1, SLC22A7, SLCO1B1, SLCO1B3, SLCO2B1) and efflux transporters (ABCB1,
      ABCB11, ABCC2, ABCC3, ABCC4, ABCG2). SOCS-3, CRP, and LBP were extensively
      induced by IL-6, with maximal induction observed at 2 (SOCS-3) and 12 hrs (CRP;
      LBP), demonstrating that the cultured human hepatocytes responded to IL-6
      treatment. In the untreated group (control), gene expression of P450 isoforms and
      uptake transporters decreased while efflux transporters remained relatively
      stable or increased with cultured duration. IL-6 predominantly caused down
      regulations of the genes studied, with the most significant changes observed at
      different treatment durations, apparently related to the stability of the basal
      levels of gene expression. For instance, for genes with unstable expression,
      which would decrease rapidly in culture (e.g CYP3A4), the most definitive down
      regulatory effects were observed at a relatively early time point (e.g. 12 hrs).
      In contrast, a longer treatment duration (e.g. 48 hrs) was required for genes
      with relatively stable expression levels in culture (e.g. ABCB1). Based on our
      findings, evaluation of multiple treatment durations rather than single treatment
      duration is recommended for the evaluation of biotherapeutics in cultured human
      hepatocytes where down regulation is expected.

PMID- 22475271
TI  - Disposition and interaction of biotherapeutics in pediatric populations.
AB  - Human development of an individual from a fertilized ovum to maturity alters the
      body anatomy and physiology. Changes of size and function, from birth onwards,
      cause significant alterations in the pharmacokinetics (PK) of drugs and
      subsequently their response pharmacodynamics (PD) in infants and children from
      those in adults. During the last three decades, hundreds of mechanistic and
      clinical pharmacology studies have been conducted to investigate the age-mediated
      changes of absorption, distribution, metabolism and excretion processes of drugs,
      which subsequently affect the pharmacology response and the safety in pediatric
      patients compared to adults. The practice of determining pediatric dose based on
      simplistic scaling of an adult dose assuming linear relationship between
      postnatal age and body weight or surface area that may lead to under prediction
      of therapeutic dose or over prediction of the dose is now under scrutiny. By
      understanding the disposition mechanism of therapeutic agents thoroughly, their
      potential drug interactions and their PK/PD relationships can be better
      determined in pediatric populations. As such, dosing regimens can be estimated
      based on actual clearance and exposure and not just by simplistic scaling of an
      adult dose. Accurate prediction of clearance in pediatrics is so critical that
      extensive translational research is warranted to improve our ability to estimate
      safe and efficacious doses in different pediatric populations from retrospective
      clinical studies in adults. Biotherapeutics, proteins and peptides-based drugs,
      generally depend on absorption (A), distribution (D), metabolism (M), and
      excretion (E) in their disposition as small molecules, but the underlying
      mechanisms and potential drug interaction propensity can be very different. In
      this article, the factors that alter pediatric and adult PK parameters are
      compared, and pediatric and adult PK parameters and potential drug interactions
      for selected biotherapeutics are summarized. Moreover, challenges of studying
      therapeutic proteins and peptides in pediatrics are discussed.

PMID- 22475272
TI  - Editorial: metabolism and drug-drug interaction potential of biotherapeutics.

PMID- 22475273
TI  - Risk of congenital heart defects is influenced by genetic variation in folate
      metabolism.
AB  - Genetic disturbances in folate metabolism may increase risk for congenital heart
      defects. We examined the association of heart defects with four polymorphisms in
      folate-related genes (methylenetetrahydrofolate reductase (MTHFR) c.677C.T, MTHFR
      c.1298A.C, methionine synthase reductase (MTRR) c.66A.G, and reduced folate
      carrier (SLC19A1) c.80A.G) in a case-control study of children (156 patients, 69
      controls) and mothers of children with heart defects (181 patients, 65 controls),
      born before folic acid fortification. MTRR c.66A.G in children modified odds
      ratios for overall heart defects, specifically ventricular septal defect and
      aortic valve stenosis (p-value below 0.05). The 66GG and AG genotypes were
      associated with decreased odds ratios for heart defects (0.42, 95% confidence
      interval (0.18-0.97) and 0.39 (0.18-0.84), respectively). This overall
      association was driven by decreased risk for ventricular septal defect for 66GG
      and AG (odds ratio 0.32 (0.11-0.91) and 0.25 (0.09-0.65)) and decreased odds
      ratio for aortic valve stenosis for 66AG (0.27 (0.09-0.79)). The association of
      ventricular septal defect and 66AG remained significant after correction for
      multiple testing (p = 0.0044, multiple testing threshold p = 0.0125). Maternal
      MTHFR 1298AC genotype was associated with increased odds ratio for aortic valve
      stenosis (2.90 (1.22-6.86), p = 0.0157), but this association did not meet the
      higher multiple testing threshold. No association between MTHFR c.677C.T or
      SLC19A1 c.80A.G and heart defect risk was found. The influence of folate-related
      polymorphisms may be specific to certain types of heart defects; larger cohorts
      of mothers and children with distinct sub-classes are required to adequately
      address risk.

PMID- 22475274
TI  - Relevance of activated leukocyte cell adhesion molecule (ALCAM) in tumor tissue
      and sera of cervical cancer patients.
AB  - BACKGROUND: An altered expression of the activated leukocyte cell adhesion
      molecule (ALCAM) is associated with cancer progression in various cancer types.
      In some cancers ALCAM has a prognostic value or is predictive for the benefit of
      therapeutic interventions. To date there are no data on the role of ALCAM in
      cervical cancer available. METHODS: In this study, ALCAM expression was analysed
      by immunohistochemistry (IHC) in tissue samples of 233 patients with cervical
      cancer, among them 178 with complete follow-up information. In addition, soluble
      (s-)ALCAM was measured in sera of a subset of the included patients (n = 55) by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: ALCAM overexpression was
      detected (immunoreactive score (IRS) 2-12) in 58.4% of the cervical cancer
      samples. The normal ectocervical or endocervical epithelium showed no ALCAM
      reactivity. In untreated patients, ALCAM overexpression in tumor tissue tended to
      be associated with shorter cancer-specific survival (CSS) and disease-free
      survival (DFS). Patients, whose tumor samples showed ALCAM overexpression
      receiving a cytotoxic therapy like radiotherapy or chemoradiation, however, had a
      favourable prognosis compared to those patients, whose cancers showed no or
      minimal ALCAM staining. This effect was particularly apparent in patients
      receiving chemoradiation where the CSS was significantly longer in patients with
      ALCAM-positive tumors (p = 0.038; cumulative incidence rates at 96 months 8%, 95%
      CI 0%-23%, and 26%, CI 3%-43% in ALCAM-positive and ALCAM-negative cases,
      respectively).Median preoperative s-ALCAM concentration in sera from tumor
      patients was 27.6 ng/ml (range 17.5-55.1 ng/ml, mean 28.9 ng/ml), serum levels
      did not correlate with intratumoral ALCAM expression. CONCLUSIONS: The data of
      our retrospective study suggest that the prognostic value of ALCAM expression in
      cervical carcinoma might be therapy-dependent, and that ALCAM might function as a
      predictive marker for the response to chemoradiation. This should be confirmed in
      further, prospective studies.

PMID- 22475275
TI  - Identification of amylase-binding monoclonal immunoglobulins in multiple myeloma
      associated with macroamylasemia.

PMID- 22475276
TI  - Risk factors for short-term virologic outcomes among HIV-infected patients
      undergoing regimen switch of combination antiretroviral therapy.
AB  - We investigated risk factors for unfavorable virologic responses among HIV
      infected patients who recently switched antiretroviral regimens. We identified
      HIV-infected patients who switched antiretroviral regimens (defined as adding >=2
      new medications) between 2001 and 2008 at Kaiser Permanente California.
      Virological response, measured after 6 months on the new regimen, was classified
      as (1) maximal viral suppression (HIV RNA <75/ml), (2) low-level viremia (LLV; 75
      5000/ml), or (3) advanced virologic failure (>5000/ml). Potential risk factors
      examined included (1) HIV disease factors, e.g., prior AIDS, CD4 cell count; (2)
      history of antiretroviral use, e.g., therapy classes of the newly switched
      regimen, medication adherence, and virologic failure at previous regimens; and
      (3) novel patient-level factors including comorbidities and healthcare
      utilization. Adjusted odds ratios (aOR) for LLV and advanced virologic failure
      were obtained from multivariable nominal logistic regression models. A total of
      3447 patients were included; 2608 (76%) achieved maximal viral suppression, 420
      (12%) had LLV, and 419 (12%) developed advanced virologic failure. Factors
      positively associated with LLV and advanced virologic failure included number of
      regimens prior to switch [aOR(per regimen)=1.38 (1.17-1.62) and 1.77 (1.50-2.08),
      respectively], nucleotide reverse transcriptase inhibitor-only regimens (vs.
      protease inhibitor-based) [aOR=2.78 (1.28-6.04) and 5.10 (2.38-10.90),
      respectively], and virologic failure at previous regimens [aOR=3.15 (2.17-4.57)
      and 4.71 (2.84-7.81), respectively]. Older age, higher CD4 cell count, and
      medication adherence were protective for unfavorable virologic outcomes.
      Antiretroviral regimen-level factors and immunodeficiency were significantly
      associated with virologic failure after a recent therapy switch and should be
      considered when making treatment change decisions.

PMID- 22475277
TI  - Therapeutic potential of mitochondrial translation inhibition for treatment of
      acute myeloid leukemia.

PMID- 22475278
TI  - Bioengineered factor Xa as a potential new strategy for hemophilia therapy.

PMID- 22475279
TI  - Bleeding risk assessment during oral anticoagulant therapy initiation.

PMID- 22475281
TI  - Romiplostim for the treatment of primary immune thrombocytopenia.
AB  - Romiplostim is a peptibody designed to evade the immune response to recombinant
      thrombopoietin and to stimulate the production of new platelets. The
      pathophysiology underlying primary immune thrombocytopenia (ITP) has shown that
      not only accelerated peripheral platelet destruction but also suppression of the
      production of new platelets can be responsible for the persistence of
      thrombocytopenia. Several prospective and well-designed trials have shown that
      weekly subcutaneous administration of romiplostim induces more durable platelet
      responses and less treatment failure compared with placebo or standard of care,
      not only in adult but also pediatric chronic ITP patients regardless of
      splenectomy status. Treatment with romiplostim also resulted in less use of
      rescue medication and permitted the majority of patients receiving concurrent ITP
      drugs to reduce or discontinue these therapies, avoiding further
      immunosuppression. Romiplostim has been shown to have overall a very favorable
      safety profile and to be well tolerated relative to other ITP treatments.

PMID- 22475282
TI  - Immunotherapy highlights from the 2011 meeting of the American Society of
      Hematology.
AB  - The world's largest hematology society, the American Society for Hematology,
      meets annually, gathering physicians, scientists, administrators, medical
      students, graduate students, allied health professionals and exhibitors. The
      meeting this year was held in San Diego, CA, USA, and included a plethora of
      basic, translational and clinical research.

PMID- 22475283
TI  - Are reduced-intensity transplants safe in older patients with hematologic
      malignancies?
AB  - Non-myeloablative allogeneic hematopoietic cell transplantation (HCT) offers a
      potentially curative therapy for older patients with hematologic malignancies.
      However, the treatment modality is underutilized and, to date, there are only
      limited data on outcomes in people older than 60 years. This study describes the
      toxicities and outcomes of non-myeloablative allogeneic HCT, conditioned with low
      dose total body irradiation with or without fludarabine, in patients aged 60-75
      years enrolled in prospective multicenter clinical trials. Increasing age was not
      associated with adverse outcome. Relapse risk and comorbidity burden predicted
      survival; fit patients with low risk of disease relapse did well after transplant
      regardless of age. Despite demonstrating the feasibility of non-myeloablative
      allogeneic HCT in patients aged 60-75 years, the study raises important questions
      regarding how best to manage older patients with high-risk hematologic
      malignancies and how to optimize our approach to allogeneic HCT in this age
      group.

PMID- 22475284
TI  - Is it time for hepcidin to join the diagnostic toolkit for iron deficiency?
AB  - The diagnostic value of hepcidin, the master regulator of iron metabolism, as an
      index of iron status is being intensively investigated. van Santen et al. have
      reported the value of hepcidin as a test for iron deficiency in both noninflamed
      and inflamed anemic patients with rheumatoid arthritis. Their data show that
      serum hepcidin identifies iron deficiency in anemic rheumatoid arthritis
      patients. Based on these results, the authors offer cutoffs for hepcidin and
      propose an algorithm to diagnose iron deficiency in this setting. This study
      provides insight into the physiology of hepcidin regulation in patients with
      coexisting iron deficiency and inflammation.

PMID- 22475286
TI  - The role of histone methyltransferase EZH2 in myelodysplastic syndromes.
AB  - Previous epigenetics research in myelodysplastic syndromes (MDS) mainly focused
      on the DNA methylation of tumor suppressor genes. Recent studies reported that
      around 6% of MDS patients have several EZH2 mutations including missense,
      frameshift and truncated mutations. Histone methyltransferase EZH2 plays a
      critical role in epigenetic regulation as a bridge between histone
      methylation/deacetylation and DNA methylation. EZH2 is frequently overexpressed
      and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as
      a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with
      poor survival. Many questions still need further discussion. Moreover, 3
      deazaneplanocin can reduce EZH2 levels and H3K27 trimethylation, and synergistic
      effects are seen in combination with DNA demethylation agents or histone
      deacetylation inhibitors. All of the above give us more chances to improve
      epigenetic therapy in MDS. Therefore, the molecular mechanisms of EZH2 in
      tumorigenesis and the role of EZH2 in MDS are studied.

PMID- 22475287
TI  - Risk stratification in Waldenstrom macroglobulinemia.
AB  - Waldenstrom macroglobulinemia is characterized by the production of serum
      monoclonal IgM and lymphoplasmacytic bone marrow infiltration. At least 25% of
      patients are asymptomatic at diagnosis and treatment is only mandatory in cases
      of symptomatic disease. Beside reports on treatment results, reviewing risk
      assessment is another way to describe the clinical course of the disease. This
      information may be particularly useful when numerous treatment options are
      available. While the introduction of new treatment approaches reinforces the need
      for careful risk assessment, the identification of useful prognostic information
      requires prolonged follow-up in patients who have not been treated with current
      therapeutic options. This limitation should be taken into account when using and
      interpreting available prognostic information, especially survival estimates.

PMID- 22475285
TI  - Pathogenesis and classification of eosinophil disorders: a review of recent
      developments in the field.
AB  - Eosinophils and their products play an essential role in the pathogenesis of
      various reactive and neoplastic disorders. Depending on the underlying disease,
      molecular defect and involved cytokines, hypereosinophilia may develop and may
      lead to organ damage. In other patients, persistent eosinophilia is accompanied
      by typical clinical findings, but the causative role and impact of eosinophilia
      remain uncertain. For patients with eosinophil-mediated organ pathology, early
      therapeutic intervention with agents reducing eosinophil counts can be effective
      in limiting or preventing irreversible organ damage. Therefore, it is important
      to approach eosinophil disorders and related syndromes early by using established
      criteria, to perform all appropriate staging investigations, and to search for
      molecular targets of therapy. In this article, we review current concepts in the
      pathogenesis and evolution of eosinophilia and eosinophil-related organ damage in
      neoplastic and non-neoplastic conditions. In addition, we discuss classifications
      of eosinophil disorders and related syndromes as well as diagnostic algorithms
      and standard treatment for various eosinophil-related disorders.

PMID- 22475289
TI  - Trauma patients at risk for massive transfusion: the role of scoring systems and
      the impact of early identification on patient outcomes.
AB  - Hemorrhage remains one of the most common causes of early death in severely
      injured patients. It is also the most common preventable cause of death in this
      population. More than 80% of deaths in the operating room and nearly 50% in the
      first 24 h after injury are related to hemorrhagic shock. Among the injured
      patients, up to 3-5% admitted to trauma centers will receive a massive
      transfusion (MT). This population may benefit from activation of MT protocols
      that are associated with decreased mortality and reduced overall blood
      transfusions. Using damage-control resuscitation and 1:1 ratios of blood
      components are associated with increased survival. However, the survival benefit
      of damage-control resuscitation and MT protocols is primarily in the first 24 h
      and is most impressive when these strategies are employed early. New scoring
      systems in conjunction with laboratory data have contributed to early objective
      identification of those patients requiring MT. Activating these protocols early
      and with an organized team approach is critical to achieving their full benefit.

PMID- 22475290
TI  - Risk and prognosis of adult primary immune thrombocytopenia.
AB  - Adult immune thrombocytopenia was previously considered a benign disease
      affecting young people and with a low risk of severe bleeding. This view was
      challenged by studies published during the past decade, as the median age of
      adult immune thrombocytopenia patients has been found to be 55-60 years and the
      incidence increases with age. Recent studies reported that mortality and
      morbidity are increased compared with the general population. In this review, we
      describe patient-specific factors associated with the outcome of disease, the
      clinical course of immune thrombocytopenia including the potential adverse impact
      of some treatments and finally the overall prognosis.

PMID- 22475288
TI  - Treating venous thromboembolism in patients with cancer.
AB  - Venous thromboembolism (VTE) is a major cause of morbidity and mortality among
      patients with cancer. Although much is known about the factors that contribute to
      VTE risk, pre-emptive therapy in high-risk populations is clearly indicated in
      only a few clinical situations. Low-molecular-weight heparin is still the
      recommended class of anticoagulants for cancer-associated VTE. Management of VTE
      in patients with renal failure, hemorrhagic brain metastases, thrombocytopenia
      and coagulopathy remains challenging with few safe and effective alternatives.
      Novel oral agents are currently being investigated and may play a role in the
      future in the treatment of cancer-associated VTE.

PMID- 22475291
TI  - Hemolytic anemia in adults: main causes and diagnostic procedures.
AB  - Hemolytic anemia is not an exceptional situation in adults. Although establishing
      the hemolytic mechanism of an anemia is usually rather easy, finding the etiology
      may be quite difficult as both hereditary (corpuscular) and acquired causes of
      hemolytic anemia may occur during adulthood. The diagnosis of hemolytic anemia,
      therefore, requires a multistep procedure taking into account both the patient's
      and family history, a careful analysis of the blood smear and a direct
      antiglobulin test. Based on these first data, the diagnostic procedure may then
      require more specific tests whose indications are discussed in this review.

PMID- 22475293
TI  - Comparison of pre-emptive and reactive strategies to control an incursion of
      bluetongue virus serotype 1 to Great Britain by vaccination.
AB  - Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV), which
      is spread between its hosts by Culicoides midges. Vaccination is the most
      effective way to protect susceptible animals against BTV and was used reactively
      to control the recent northern European outbreak. To assess the consequences of
      using vaccination pre-emptively we used a stochastic, spatially explicit model to
      compare reactive and pre-emptive vaccination strategies against an incursion of
      BTV serotype 1 (BTV-1) into Great Britain. Both pre-emptive and reactive
      vaccination significantly reduced the number of affected farms and limited host
      morbidity and mortality. In addition, vaccinating prior to the introduction of
      disease reduced the probability of an outbreak occurring. Of the strategies
      simulated, widespread reactive vaccination resulted in the lowest levels of
      morbidity. The predicted effects of vaccination were found to be sensitive to
      vaccine efficacy but not to the choice of transmission kernel.

PMID- 22475294
TI  - Time course of free-choice priming effects explained by a simple accumulator
      model.
AB  - Unconscious visual stimuli can be processed by human observers and modulate their
      behavior. This has been shown for masked prime stimuli that influence motor
      responses to subsequent target stimuli. Beyond this, masked stimuli can also
      affect participants' behavior when they are free to choose one of two response
      alternatives. This finding demonstrates that an apparently free-choice between
      alternative behaviors can be subject to influences that are outside of awareness.
      We report three experiments which exhibit that the temporal dynamic of free
      choice priming effects corresponds to that of forced-choice priming effects.
      Forced-choice priming effects were relatively robust against variations of prime
      stimuli but sensitive to physical features of target stimuli. Free-choice priming
      effects, in contrast, depended largely on the stimulus-response compatibility of
      the prime. A simple accumulator model which accounts for forced-choice response
      priming can also explain free-choice priming effects by the assumption that
      unconscious stimuli can initiate motor responses when participants are engaged in
      a speeded choice-reaction time task. According to our analyses free-choice
      priming results from a response selection mechanism which integrates conscious
      and unconscious information from external, stimulus driven sources and also from
      internal sources.

PMID- 22475295
TI  - The time course of argument reactivation revealed: using the visual world
      paradigm.
AB  - Previous research has found that the single argument of unaccusative verbs (such
      as fall) is reactivated during sentence processing, but the argument of agentive
      verbs (such as jump) is not (Bever & Sanz, 1997; Friedmann, Taranto, Shapiro, &
      Swinney, 2008). An open question so far was whether this difference in processing
      is caused by a difference in thematic roles the verbs assign, or a difference in
      the underlying syntactic structure. In the present study we tease apart these two
      potential sources. In order to achieve this, we included a set of verbs (like
      sparkle) which are equal to unaccusative verbs in the thematic role they assign
      to their argument, but equal to agentive verbs in the syntactic status of their
      argument (henceforth mixed verbs). As a method we used the visual world paradigm
      as this enables us to measure processing of the sentences continuously. This
      method also allowed us to test another hypothesis, namely the hypothesis that not
      only the argument of unaccusative verbs is reactivated during processing, but
      also the argument of agentive verbs. This reactivation is expected as the result
      of integrating the verb and its argument into one representation. In our
      experiment, participants listened to sentences including one of the three types
      of verbs. While listening, they viewed a visual display in which one of four
      objects was strongly related to the argument of the verb (wood-saw). The gaze
      record showed that the eyes moved to the related object (saw) upon presentation
      of the argument (wood). More interestingly, the eyes moved back to the related
      object upon presentation of the verb (fell). We found that looks to the related
      object increase only late after verb offset for unaccusative verbs, replicating
      the findings of previous research. We also found a rise in looks to the related
      object in agentive verbs, but this rise took place much earlier, starting
      slightly after verb onset. Finally, we found that mixed verbs pattern in
      processing with agentive verbs. We conclude that the argument of the verb is
      always reactivated, independent of verb type. In addition, the timing of
      integration differs per verb type and depends on the syntactic status of the
      argument and not on the thematic role that is assigned to the argument.

PMID- 22475296
TI  - Hemophagocytic lymphohistiocytosis in 2 pediatric patients secondary to hepatitis
      A virus infection.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome
      characterized by uncontrolled activation of cytotoxic T cells and antigen
      presenting cells. Common clinical manifestations include high fever,
      maculopapular rash, neurological symptoms, coagulopathy, and abnormal liver
      function tests [1]. HLH can be either primary, that is, due to an underlying
      genetic defect, or secondary, associated with malignancies, autoimmune diseases,
      or infections. The true incidence of secondary HLH is difficult to define.
      Infection associated HLH are most commonly associated with viral infections
      mainly of the herpes group, with Epstein-Barr virus (EBV) that is proposed to be
      the most common cause [2]. Despite the high incidence of hepatitis A virus (HAV)
      infection in the pediatric population in general, there are few pediatric case
      reports in the literature about HAV-associated hemophagocytic syndrome [3]. We
      encountered 2 patients with HAV-associated hemophagocytic syndrome.

PMID- 22475297
TI  - Primary hemophagocytic lymphohistiocytosis in Iran: report from a single referral
      center.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by
      fever, hepatosplenomegaly, and cytopenia, and widespread accumulation of
      lymphocytes and histiocytes, sometimes with hemophagocytosis, primarily involving
      the spleen, lymph nodes, bone marrow, and liver. HLH can either occur
      sporadically (secondary HLH) or as part of a familial syndrome (primary HLH),
      including familial HLH and the distinct immunodeficiency syndromes. Herein the
      authors report 6 Iranian patients with primary HLH and their outcome from a
      single tertiary-care center.

PMID- 22475298
TI  - Assessment of cardiac parameters in evaluation of cardiac functions in patients
      with thalassemia major.
AB  - The aim of the study was to evaluate cardiac function and early cardiac
      dysfunction of patients followed as thalassemia major. In this study, the authors
      compared 100 patients, diagnosed as thalassemia major with mean age 11.84 +/-
      4.35, with 60 healthy control subjects at the same age between 2008 and 2011.
      Early diagnosis of iron overload that may occur after repeated transfusions is
      important in this patient group. To detect early iron accumulation, the authors
      compared ferritin with the echo findings, the 24-hour Holter, and cardiac
      magnetic resonance imaging (MRI) T2* values in the patients of same age and sex,
      treated with chelators, without heart failure, nonsplenectomized, and do not
      differ in the presence of hepatitis C. Ferritin levels, left ventricular systolic
      functions (ejection fraction [EF], shortening fraction [SF]), left ventricular
      measurements, left ventricular diastolic functions, T2* image on cardiac magnetic
      resonance, heart rate variables in 24 hours, and Holter rhythm were evaluated to
      show the early failure of cardiac functions. In this study the authors confirmed
      that iron-related cardiac toxicity damages electrical activity earlier than
      myocardial contractility. Left ventricular diastolic diameter (LVDd), left
      ventricular mass (LVM), and LV systolic diameter (LVDs) levels were significantly
      higher in the patient group with ectopia. Patients with ectopia are the ones in
      whom LVM and LVDd are increased. In thalassemia major patients with ectopia,
      LF/HF ratio was markedly increased, QTc dispersion was clearly found higher in
      patients with ectopia rather than nonectopic patients. The standard deviation all
      normal RR interval series (SDNN) was found clearly lower in thalassemia major
      group with ectopia than control group because it is assumed that increase in
      cardiac sympathetic neuronal activity is related to exposure to chronic diastolic
      and systolic failure.

PMID- 22475299
TI  - Autoimmune hemolytic anemia in patients with beta-thalassemia major.
AB  - Hemolysis is a common feature in patients with beta-thalassemia major. As a
      result, autoimmune hemolytic anemia complicating beta-thalassemia is easily
      overlooked. Here, the authors described the clinical features and management of 7
      patients with beta-thalassemia major and autoimmune hemolytic anemia. These
      patients had fever, cough, and tea-colored urine on admission. The laboratory
      investigations showed a significant drop in hemoglobin and increased serum
      bilirubin. Coombs' tests revealed that anti-immunoglobulin G (IgG) and anti-C3
      was positive in 7 and 5 cases, respectively, whereas anti-Rh E alloantibody was
      positive in 3 cases. All the patients received corticosteroids treatments and
      blood transfusions. Patients with anti-Rh E alloantibodies also received
      immunoglobulin treatments. Six of the patients responded well to the management,
      but 1 patient developed recurrent autoimmune hemolytic anemia that required
      cyclosporin A treatment. All the patients remained well by following up for more
      than 6 months.

PMID- 22475300
TI  - alpha-Thalassemia frequency and mutations in children with hypochromic microcytic
      anemias and relation with beta-thalassemia, iron deficiency anemia.
AB  - The majority of the anemias during childhood are hypochromic and microcytic. The
      aim of the present study was to determine the status of alpha-thalassemia
      mutations and its association with other etiologies, such as iron deficiency
      anemia (IDA) and beta-thalassemia trait, that are frequently seen hypochromic
      microcytic anemias in children. Children with hypochromic microcytic anemias were
      included in the study. Serum iron (SI), total iron-binding capacity (TIBC),
      ferritin levels, and hemoglobin electrophoresis with high-performance liquid
      chromatography (HPLC) method were analyzed. Reverse hybridization of biotinylated
      polymerase chain reaction (PCR) product method was used for detection of alpha
      globin gene mutations. Of the 46 patients involved in the study, 54.3% (n = 25)
      were boys, and 45.7% (n = 21) were girls. Iron deficiency anemia and beta
      thalassemia trait were diagnosed in 67.4% (n = 31) and 19.5% (n = 9),
      respectively. In 17.4% there were alpha-thalassemia mutations (in 10.9% 3.7
      single-gene heterozygote mutation, in 4.3% 20.5-kb double-gene deletion mutation,
      and in 2.2% alpha-2 poly-A-1 heterozygote mutation was detected). In 2 patients
      (4.3%) no etiology was determined. In 2 patients (4.3%) association between iron
      deficiency anemia and alpha-thalassemia, in 1 patient (2.2%) association between
      beta and alpha-thalassemia was detected. In conclusion, alpha-thalassemia carrier
      status and its association with other etiologies are frequently seen in Manisa.
      So, alpha-thalassemia should be considered in the differential diagnosis of
      hypochromic microcytic anemias, especially in cases without iron deficiency (ID)
      and beta-thalassemia carrier state.

PMID- 22475301
TI  - D-dimer and portal vein status in splenectomized Egyptian beta-thalassemia major
      patients: a prospective single-thalassemia center experience.
AB  - Splenectomy is a recognized cause of portal vein thrombosis. Thirty-six beta
      thalassemia major (beta-TM) patients were followed up for 36 months to evaluate
      changes in D-dimer levels (as a possible marker for thrombosis development) and
      portal vein status (by portal duplex ultrasound) at both early and late
      postlaparoscopic splenectomy periods. They were classified into group I if they
      were splenectomized in the study period (n = 12), or group II if they were
      splenectomized during the 5 years preceding the period (n = 24). In group I, D
      dimer was measured 5 times: 1 day presplenectomy, the 1st week, 6th week, and 6th
      month postsplenectomy, and at the study end, whereas in group II, D-dimer was
      measured twice: at the study entry and end. Portal duplex was done 1 week
      postsplenectomy (group I) and at study end in both groups. Presplenectomy D-dimer
      levels in group I were significantly higher compared with the 6th month (P =
      .042) and study end (P = .03), whereas 1st week (postsplenectomy) D-dimer levels
      had a high mean of 3497.3 ng/mL, lowered at the 6th week (P = .017), at the 6th
      month (P = .008), and at study end (P = .005). D-dimer levels in group II showed
      no difference between study entry and end (P = .104). Portal vein "diameter and
      flow" were within normal findings in both groups. In this 3-year prospective
      study, a subclinical hypercoagulable state was detected 1 day prior to
      splenectomy and in the early postsplenectomy period, as evidenced by high D-dimer
      levels. Laparoscopic splenectomy was not associated with portal venous thrombosis
      either clinically or by duplex sonography.

PMID- 22475302
TI  - Vitamin D deficiency and comorbidities in children with sickle cell anemia.
AB  - Vitamin D deficiency is known to be common among patients with sickle cell anemia
      (SCA). Vitamin D levels were measured in 139 children (aged 7.9 to 15.1 years) to
      study its association with SCA morbidities; severe deficiency <10 ng/mL was
      present in 64.0% and only 2.2% were sufficient (>30 ng/mL). Vitamin D levels were
      associated with pulmonary function (forced expiratory volume in 1 second
      [FEV(1)]), but not associated with either rates of acute pain or acute chest
      syndrome episodes. Further studies are needed to be able to compare outcomes in
      those with deficiency to those with sufficiency, as well as to treating patients
      with SCA with vitamin D to better establish a possible link, if any, between
      vitamin D and SCA morbidity.

PMID- 22475303
TI  - Rhabdomyolysis in a child with Hemoglobin SE.

PMID- 22475304
TI  - Osteosarcoma following growth hormone therapy in recurrent acute lymphoblastic
      leukemia and Rapadilino syndrome.

PMID- 22475305
TI  - In vivo effect of recombinant human granulocyte colony-stimulating factor on
      neutrophilic expression of CD11b in septic neonates: a randomized controlled
      trial.
AB  - Neonates are susceptible to septicemia secondary to quantitative and qualitative
      neutrophilic defects. Granulocyte colony-stimulating factor (G-CSF) stimulates
      myeloid progenitor cell proliferation and induces selective neutrophil functions.
      The authors aimed to evaluate the effect of G-CSF administration in septic
      neonates on neutrophil production and CD11b expression. Sixty septic neonates
      were randomized to receive intravenous G-CSF 10 MUg/kg/day for 3 days (G-CSF
      group, n = 30), or not to receive G-CSF (non-G-CSF group, n = 30). Thirty healthy
      newborns were included as controls. Laboratory investigations included complete
      blood count, C-reactive protein, blood culture, renal and liver function tests,
      and assessment of neutrophilic expression of CD11b. Total leukocytes count (TLC),
      absolute neutrophil count (ANC), and immature myeloid cell count in G-CSF group
      showed significant difference between post-and pre-G-CSF levels. TLC, ANC,
      immature myeloid cell count and immature/total myeloid cells ratio were higher in
      G-CSF group compared to non-G-CSF group on days 1 and 3. Higher neutrophilic
      expression of CD11b was reported in both septic groups on day 0 compared to
      control group. On day 5, CD11b was higher in G-CSF group than non-G-CSF group. G
      CSF improved CD11b% in neutropenic and non-neutropenic septic neonates. No
      significant difference was found between pre- and posttreatment renal and liver
      function tests. Lower duration of antibiotic intake and hospitalization was
      observed in G-CSF group compared to non-G-CSF group. G-CSF administration as an
      adjuvant therapy for neonatal septicemia, whether neutropenic or not, improves
      neutrophilic count and function and contributed to early healing from sepsis.

PMID- 22475306
TI  - Honey and a mixture of honey, beeswax, and olive oil-propolis extract in
      treatment of chemotherapy-induced oral mucositis: a randomized controlled pilot
      study.
AB  - In spite of being one of the most investigated subjects among supportive care in
      cancer, no therapy has been found effective in treatment of chemotherapy-induced
      oral mucositis. Based on the observations that honey bees products have anti
      inflammatory and wound healing effects, the present study tried to evaluate the
      effect of topical application of honey and a mixture of honey, olive oil-propolis
      extract, and beeswax (HOPE) in treatment of oral mucositis. This was a randomized
      controlled clinical trial conducted on 90 patients with acute lymphoblastic
      leukemia and oral mucositis grades 2 and 3. The mean age of enrolled patients was
      6.9 years. The patients were assigned into 3 equal treatment groups: Honey, HOPE,
      and control groups. Topical treatment for each patient consists of honey, HOPE,
      and benzocaine gel for honey, HOPE, and control groups, respectively. Recovery
      time in grade 2 mucositis was significantly reduced in the honey group as
      compared with either HOPE or controls (P < .05). In grade 3 mucositis, recovery
      time did not differ significantly between honey and HOPE (P = 0.61) but compared
      with controls, healing was faster with either honey or HOPE (P < .01). Generally,
      in both grades of mucositis, honey produced faster healing than either HOPE or
      controls (P < .05). Based on our results that showed that honey produced faster
      healing in patients with grade 2/3 chemotherapy-induced mucositis, we recommend
      using honey and possibly other bee products and olive oil in future therapeutic
      trials targeting chemotherapy-induced mucositis.

PMID- 22475307
TI  - The influence of media characters on children's food choices.
AB  - Two experiments were conducted to assess the role of media characters in
      influencing children's food choices; the first focused on children's self
      reported preference, whereas the second focused on actual choice. The results of
      the experiments suggest that popular characters can make a difference in
      encouraging children to select one food over another. In the first experiment,
      children were more likely to indicate a preference for one food over another when
      one was associated with characters that they liked and with whom they were
      familiar. This effect was particularly strong when a sugary or salty snack
      branded by a favored character was competing with a healthier option branded by
      an unknown character or no character. Alternatively, when children were asked to
      choose between a healthy food and a sugary or salty snack, branding of the
      healthy food with a favored character did not significantly change appeal of that
      healthy snack. However, when foods within the same category (i.e., 2 vegetables,
      2 fruits, or 2 grains) were asked to compete against each other, character
      branding strongly influenced children's food choice. Findings from the second
      experiment suggest that children are more willing to try more pieces of a healthy
      food if a favored character, in comparison with an unknown character, is
      promoting that food.

PMID- 22475308
TI  - Bis-spirolabdane diterpenoids from Leonotis nepetaefolia.
AB  - Ten new bis-spirolabdane diterpenoids, leonepetaefolins A-E (1, 3, 5, 7, 9) and
      15-epi-leonepetaefolins A-E (2, 4, 6, 8, 10), together with eight known labdane
      diterpenoids (11-18) as well as two known flavonoids, apigenin and cirsiliol,
      were isolated from the leaves of Leonotis nepetaefolia. The structures of the new
      compounds were determined on the basis of 1D- and 2D-NMR experiments including
      (1)H, (13)C, DEPT, (1)H-(1)H COSY, HSQC, HMBC, and NOESY. The absolute
      configuration of an epimeric mixture of 1 and 2 was determined by X-ray
      crystallographic analysis. The compounds isolated were evaluated for their
      binding propensity in several CNS G-protein-coupled receptor assays in vitro.

PMID- 22475309
TI  - [Neutrophilic urticaria or urticaria with predominantly neutrophilic inflammatory
      infiltrate: study of its clinical and histopathologic characteristics and its
      possible association with rheumatic disease].
AB  - INTRODUCTION: Neutrophilic urticaria, described by Winkelmann in 1985, has yet to
      be completely defined and its clinical significance is poorly understood.
      Nevertheless, recent publications suggest that it could be a marker for rheumatic
      disease. The primary objective of this study was to compare the prevalence of
      rheumatic disease in 2 groups of patients with urticaria: those with conventional
      urticaria (non-neutrophilic inflammatory infiltrate) and those with neutrophilic
      urticaria. MATERIAL AND METHODS: We retrospectively reviewed all biopsy samples
      taken from urticarial lesions in our hospital between January 1, 1999 and June
      28, 2009. Urticaria was classified according to predefined morphologic and
      histopathologic patterns. We compared the clinical and histologic characteristics
      of neutrophilic urticaria with those of conventional urticarias in the 84
      patients included. RESULTS: Of the 84 patients, 57.1% had neutrophilic urticaria.
      We did not find significant differences between the percentages of patients with
      rheumatic disease between the neutrophilic and nonneutrophilic urticaria groups.
      In patients with acute urticaria, we found a significantly higher proportion of
      samples with histopathologic signs of neutrophilic urticaria as opposed to
      conventional histopathology. Patients with neutrophilic urticaria also had higher
      white blood cell counts. CONCLUSIONS: The percentage of samples with neutrophilic
      urticaria in this series (57.1%) is higher than the percentages reported in the
      literature, possibly because we tended to biopsy recent lesions. We highlight
      that the presence of neutrophils in the biopsies of urticaria is a common finding
      and does not appear to be associated with other diseases.

PMID- 22475310
TI  - Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric
      acute lymphoblastic leukemia.
AB  - Analysis of the microRNA transcriptome following dexa- methasone treatment of the
      acute lymphocytic leukemia (ALL) cell line RS4;11 showed a global down-regulation
      of microRNA levels. MIR17HG was rapidly down-regulated following treatment, with
      chromatin immunoprecipitation (ChIP) analysis demonstrating the promoter to be a
      direct target of glucocorticoid (GC)-transcriptional repression and revealing the
      miR17-92 cluster as a prime target for dexamethasone-induced repression. The loss
      of miR17 family expression and concomitant increases in the miR17 target Bim
      occurred in an additional ALL cell line SUP-B15 but not in the dexamethasone
      resistant REH. Alteration of miR17 levels through up-regulation or inhibition
      resulted in an decrease and increase, respectively, in Bim protein levels and
      dexamethasone-induced cell death. Primary ex vivo ALL cells that underwent
      apoptosis induced by dexamethasone also down-regulated miR17 levels. Thus, down
      regulation of miR17 plays an important role in glucocorticoid-induced cell death
      suggesting that targeting miR17 may improve the current ALL combination therapy.

PMID- 22475311
TI  - Clinical and biological factors that contribute to thrombin generation in
      prothrombin G20210A carriers: a case-control study in a single Thrombophilia
      Center.

PMID- 22475312
TI  - Monomeric C-reactive protein alters fibrin clot properties on endothelial cells.
AB  - Elevated plasma levels of C-reactive protein (CRP) are independently associated
      with increased risk of atherothrombosis. Several lines of evidence suggest that
      CRP has prothrombogenic effects on injured vessel wall(s) by enhancing tissue
      factor (TF) expression. Abnormal fibrin formation is correlated with increased
      thrombotic risk. However, the impact of localized, cell surface-driven in situ
      tissue factor generation by CRP on clot dynamics and fibrin architecture has not
      previously been evaluated. We examined the impact of native CRP and modified or
      monomeric CRP (mCRP) on the fibrin formation and structure in Human Umbilical
      Vein Endothelial Cells (HUVECs). Fibrin formation and structure were examined
      using laser scanning confocal microscopy. Incubation with mCRP on the cell
      surface had faster fibrin polymerization by the analysis of turbidimetry.
      Confocal microscopy of fibrin clots showed a significantly increased density in
      the treatment of mCRP compared with native CRP and control in the proximal versus
      distal relationship to the cell surface. The increased expression and activity of
      TF on the cell surface was observed by addition of mCRP. Blockage of tissue
      factor and lipid rafts significantly reduced the density of fibrin network
      produced by mCRP-stimulated endothelial cells. mCRP changes clot dynamics and
      alters fibrin architecture by enhancing TF on the endothelial cell surface. These
      results support the concept that elevated CRP levels may induce fibrinolytic
      resistance and endothelial dysfunction by altering fibrin clot structure.

PMID- 22475313
TI  - Derivation and validation of a multivariate model to predict mortality from
      pulmonary embolism with cancer: The POMPE-C tool.
AB  - BACKGROUND: Clinical guidelines recommend risk stratification of patients with
      acute pulmonary embolism (PE). Active cancer increases risk of PE and worsens
      prognosis, but also causes incidental PE that may be discovered during cancer
      staging. No quantitative decision instrument has been derived specifically for
      patients with active cancer and PE. METHODS: Classification and regression
      technique was used to reduce 25 variables prospectively collected from 408
      patients with AC and PE. Selected variables were transformed into a logistic
      regression model, termed POMPE-C, and compared with the pulmonary embolism
      severity index (PESI) score to predict the outcome variable of death within 30
      days. Validation was performed in an independent sample of 182 patients with
      active cancer and PE. RESULTS: POMPE-C included eight predictors: body mass,
      heart rate >100, respiratory rate, SaO2%, respiratory distress, altered mental
      status, do not resuscitate status, and unilateral limb swelling. In the
      derivation set, the area under the ROC curve for POMPE-C was 0.84 (95% CI: 0.82
      0.87), significantly greater than PESI (0.68, 0.60-0.76). In the validation
      sample, POMPE-C had an AUC of 0.86 (0.78-0.93). No patient with POMPE-C estimate
      <= 5% died within 30 days (0/50, 0-7%), whereas 10/13 (77%, 46-95%) with POMPE-C
      estimate >50% died within 30 days. CONCLUSION: In patients with active cancer and
      PE, POMPE-C demonstrated good prognostic accuracy for 30 day mortality and better
      performance than PESI. If validated in a large sample, POMPE-C may provide a
      quantitative basis to decide treatment options for PE discovered during cancer
      staging and with advanced cancer.

PMID- 22475314
TI  - Theragnostic performance of ex vivo testing of haemostatic intervention and
      clinical effect of recombinant factor VIIa and fibrinogen concentrate.

PMID- 22475316
TI  - Source contributions to atmospheric gases and particulate matter in the
      southeastern United States.
AB  - A new approach for determining the contributions of emission sources to
      concentrations of particulate matter and gases is developed using the chemical
      mass balance (CMB) method and the U.S. EPA's National Emission Inventory (NEI).
      The approach apportions combined gas-phase and condensed-phase concentrations of
      individual compounds as well as PM(2.5) mass. Because the NEI is used to provide
      source emission profiles for CMB analysis, the method generates information on
      the consistency of the NEI with ambient monitoring data. The method also tracks
      secondary species to primary source emissions, permitting a more complete
      accounting of the impact of aggregated source types on PM(2.5) mass
      concentrations. An example application is presented using four years of
      monitoring data collected at eight sites in the Southeastern Aerosol Research and
      Characterization (SEARCH) network. Including both primary and secondary species,
      area sources contributed 2.0-3.7 MUg m(-3) (13-26%), point sources contributed
      3.0-4.6 MUg m(-3) (22-33%), and mobile sources contributed 1.0-6.0 MUg m(-3) (9
      42%) to mean PM(2.5) mass concentrations. Whereas the NEI generally accounts for
      the ambient concentrations of gases and particles, certain anomalies are
      identified, especially related to carbonaceous compounds and dust.

PMID- 22475315
TI  - The risk of postpartum hemorrhage in women using high dose of low-molecular
      weight heparins during pregnancy.
AB  - BACKGROUND: Low-molecular-weight heparins (LMWH) are the most commonly used
      anticoagulant during pregnancy for prevention or treatment of VTE. However, the
      size of the associated risk of postpartum haemorrhage (PPH) is unknown.
      OBJECTIVE: To assess the bleeding risk of high dose LMWH, also in relation to
      time between last dose LMWH and delivery. MATERIAL AND METHODS: From 1999 to
      2009, we followed 88 pregnant women who were started on therapeutic
      anticoagulation. Controls were pregnant women without LMWH, matched 1:4 for
      parity, mode of delivery, age, gestational age and delivery date. PPH was defined
      as >500 ml blood loss for vaginal delivery (severe PPH in vaginal delivery as
      >1000 ml) and >1000 ml for cesarean section (CS). Women were divided into
      subgroups by the interval between last dose of anticoagulation and delivery (<12,
      12-24 hrs, >24 hrs). RESULTS: Risk of PPH after vaginal delivery was 30% and 18%
      for LMWH-users and non-users, respectively (OR 1.9, 95%CI 1.1-3.5). Risk of
      severe PPH after vaginal delivery was not different (5.6 vs 5.0%; OR 1.1; 0.4
      3.6). Risk of PPH after CS was 12% in LMWH-users and 4% in non-users (OR 2.9; 0.5
      19.4). Both events of LMWH-users occurred after emergency CS. The risk of PPH
      associated with delivery within 24 hours after last dose of LMWH was 1.2 fold
      higher (95%CI 0.4-3.6) compared to a larger interval. CONCLUSION: High dose LMWH
      carries an increased risk of more than 500 mL blood loss after vaginal delivery.
      However, this results not in more clinical relevant severe PPHs. The interval
      between last dose of LMWH and delivery does not influence the risk of PPH.

PMID- 22475317
TI  - A berry thought-provoking idea: the potential role of plant polyphenols in the
      treatment of age-related cognitive disorders.
AB  - Today, tens of millions of elderly individuals worldwide suffer from dementia.
      While the pathogenesis of dementia is complex and incompletely understood, it may
      be, at least to a certain extent, the consequence of systemic vascular pathology.
      The metabolic syndrome and its individual components induce a proinflammatory
      state that damages blood vessels. This condition of chronic inflammation may
      damage the vasculature of the brain or be directly neurotoxic. Associations have
      been established between the metabolic syndrome, its constituents and dementia. A
      relationship has also been observed between certain dietary factors, such as
      constituents of the 'Mediterranean diet', and the metabolic syndrome; similar
      associations have been noted between these dietary factors and dementia. Fruit
      juices and extracts are under investigation as treatments for cognitive
      impairment. Blueberry, strawberry, blackberry, grape and plum juices or extracts
      have been successfully tested in cognitively impaired rodents. Published trials
      of the benefits of grape and blueberry juice in the treatment of small numbers of
      cognitively impaired persons have recently appeared. The benefits of fruit
      products are thought to be a result of its polyphenol content. A grape polyphenol
      found in grapes, resveratrol, now being studied in humans, and one in grapes and
      blueberries, pterostilbene, have been found to improve cognition in rodents. In
      the design of future human trials, one ought to consider the poor bioavailability
      of these products, the possible need to initiate the experimental therapy long
      before the onset of symptoms, and currently limited knowledge about the
      appropriate form (e.g. juice, powder or individual polyphenol) of treatment.

PMID- 22475318
TI  - Asymmetric total synthesis and absolute stereochemistry of the neuroactive marine
      macrolide palmyrolide A.
AB  - The first asymmetric total synthesis and determination of the absolute
      configuration for the neuroactive marine macrolide palmyrolide A is described.
      The highlight of the synthesis is macrocyclization via trans-enamide formation
      catalyzed by copper(I) iodide and cesium carbonate. Comparison with the authentic
      spectral data confirms the synthesis of (+)-ent-palmyrolide A.

PMID- 22475319
TI  - Recovery and subsequent recurrence in patients with recurrent major depressive
      disorder.
AB  - In contrast to "remission" from an episode of major depressive disorder (MDD),
      for which there is general agreement in the literature, the optimal definition of
      "recovery" from MDD is uncertain. Previous definitions of recovery have used
      inconsistent thresholds for symptom severity and duration of wellness. To address
      the effects of duration and degree of recovery from an episode of MDD on
      recurrence risk, and the impact of maintenance antidepressant treatment on
      recurrence, we analyzed 258 patients from a randomized, double-blind study of
      outpatients with recurrent MDD. All patients had responded to 81/2 months of
      venlafaxine extended release and were subsequently randomized to receive
      venlafaxine ER or placebo during 2 consecutive 12-month maintenance phases. Four
      definitions of recovery were used to evaluate recovery rates and time to
      recurrence: (1) 17-item Hamilton Depression Rating Scale (HAM-D(17)) total score
      <=3 with duration >=120 days; (2) HAM-D(17) <=3 with duration >=56 days; (3) HAM
      D(17) <=7 with duration >=120 days; and (4) HAM-D(17) <=7 with duration >=56
      days. Recovery definitions using lower symptom severity and longer duration
      thresholds produced lower rates of recurrence. Patients on placebo were more
      likely to have a recurrence than patients on venlafaxine ER, with hazard ratio
      (HR) ranging from 2.5 among patients who recovered by the most relaxed criteria
      (definition 4), to 5.3 among patients who recovered by the most stringent
      criteria (definition 1). We conclude that protection against recurrence derives
      from the degree and duration of recovery, particularly for patients maintained on
      antidepressant medication.

PMID- 22475320
TI  - Behaviorally-indexed distress tolerance and suicidality.
AB  - Research indicates that distress tolerance exhibits a complicated relationship
      with risk factors for suicidal behavior. Specifically, low self-reported distress
      tolerance has been linked to perceived burdensomeness and thwarted belongingness.
      Contrastingly, high self-reported distress tolerance has been linked to the
      acquired capability for suicide. Given the frequently discrepant findings between
      self-report and behavioral indices of distress tolerance, we sought to expand
      upon prior findings by testing these relationships utilizing a behavioral measure
      of distress tolerance. Additionally, in an effort to further clarify the role of
      distress tolerance relative to painful and/or provocative experiences in the
      acquired capability, we examined whether distress tolerance serves as a
      moderator. Results revealed no significant associations between distress
      tolerance and burdensomeness or belongingness; however, distress tolerance was
      positively associated with the acquired capability. Furthermore, the interaction
      of distress tolerance and painful and/or provocative experiences significantly
      predicted the acquired capability, with the strength of the association
      increasing at higher levels of distress tolerance. Results highlight the
      potential importance of perceived versus actual ability to tolerate distress with
      respect to suicidal desire. In contrast, the results reflect the importance of
      actual persistence in the acquired capability.

PMID- 22475321
TI  - Dopamine response to psychosocial stress in humans and its relationship to
      individual differences in personality traits.
AB  - BACKGROUND: Previous studies have reported inter-individual variability in the
      dopamine (DA) response to stress. This variability might be related to individual
      differences in the vulnerability to experience the negative effect of stress.
      OBJECTIVE: To investigate whether personality traits as measured by the revised
      NEO personality inventory explain variability in DA response to a psychosocial
      stress task. METHODS: Eleven healthy adults, mean age of 26 +/- 3.87 underwent
      two positron emission tomography (PET) scans using the dopamine D(2/3) agonist,
      [11C]-(+)-PHNO under a control and stress condition. The simplified reference
      tissue model (SRTM) was used to obtain [11C]-(+)-PHNO binding potential (BP(ND)).
      Stress-induced DA response was indexed as a percent change in [11C]-(+)-PHNO
      BP(ND) between control and stress conditions. The regions of interest were
      defined into D2-rich regions, which included the Associative and Sensorimotor
      Striatum (AST and SMST); D(2/3) mixed regions, which included the limbic striatum
      (LST) and globus pallidus (GP); and D3-rich region, which included the Substantia
      Nigra (SN). RESULTS: Several personality traits within the Neuroticism and
      Openness to Experience domain were significantly correlated with blunted DA
      response to stress. Specifically, the Angry-Hostility, Vulnerability, and
      Depression trait were associated with blunted DA stress response in the AST (r = 
      0.645, p = 0.032), LST (r = -0.677, p = 0.022) and GP (r = -0.736, p = 0.010),
      respectively. The Openness to Values was correlated with a decreased DA release
      in the SN (r = -0.706, p = 0.015). CONCLUSION: Variability in DA stress response
      might be related to individual differences in personality.

PMID- 22475323
TI  - The five-factor narcissism inventory: a five-factor measure of narcissistic
      personality traits.
AB  - This study provides convergent, discriminant, and incremental validity data for a
      new measure of narcissistic personality traits created from the perspective of
      the Five-factor model (FFM) of general personality structure. Fifteen scales were
      constructed as maladaptive variants of respective facets of the FFM (e.g.,
      Reactive Anger as a narcissistic variant of angry hostility), with item selection
      made on the basis of a criterion-keying approach using results from 167
      undergraduates. On the basis of data from 166 additional undergraduates, the
      convergent validity of these 15 scales was tested with respect to 8 established
      measures of narcissism (including measures of both grandiose and vulnerable
      narcissism) and the respective facets of the FFM. Discriminant validity was
      tested with respect to facets from other FFM domains. Incremental validity was
      tested with respect to the ability of the FFM narcissism trait scales to account
      for variance in 2 alternative measures of narcissism, after variance accounted
      for by respective NEO PI-R facet scales and other established measures of
      narcissism were first removed. The findings support the validity of these new
      scales as measures of narcissistic personality traits and as maladaptive variants
      of the FFM.

PMID- 22475322
TI  - Comparison of growth factor signalling pathway utilisation in cultured normal
      melanocytes and melanoma cell lines.
AB  - BACKGROUND: The phosphatidylinositol-3-kinase (PI3K-PKB), mitogen activated
      protein kinase (MEK-ERK) and the mammalian target of rapamycin (mTOR- p70S6K),
      are thought to regulate many aspects of tumour cell proliferation and survival.
      We have examined the utilisation of these three signalling pathways in a number
      of cell lines derived from patients with metastatic malignant melanoma of known
      PIK3CA, PTEN, NRAS and BRAF mutational status. METHODS: Western blotting was used
      to compare the phosphorylation status of components of the PI3K-PKB, MEK-ERK and
      mTOR-p70S6K signalling pathways, as indices of pathway utilisation. RESULTS:
      Normal melanocytes could not be distinguished from melanoma cells on the basis of
      pathway utilisation when grown in the presence of serum, but could be
      distinguished upon serum starvation, where signalling protein phosphorylation was
      generally abrogated. Surprisingly, the differential utilisation of individual
      pathways was not consistently associated with the presence of an oncogenic or
      tumour suppressor mutation of genes in these pathways. CONCLUSION: Utilisation of
      the PI3K-PKB, MEK-ERK and mTOR-p70S6K signalling pathways in melanoma, as
      determined by phosphorylation of signalling components, varies widely across a
      series of cell lines, and does not directly reflect mutation of genes coding
      these components. The main difference between cultured normal melanocytes and
      melanoma cells is not the pathway utilisation itself, but rather in the serum
      dependence of pathway utilisation.

PMID- 22475324
TI  - Rituximab and bendamustine in patients with CD20+ diffuse large B-cell lymphoma
      not eligible for cyclophosphamide, doxorubicin, vincristine and prednisone-like
      chemotherapy.

PMID- 22475325
TI  - Cationic spacer arm design strategy for control of antimicrobial activity and
      conformation of amphiphilic methacrylate random copolymers.
AB  - Antimicrobial and hemolytic activities of amphiphilic random copolymers were
      modulated by the structure of the cationic side chain spacer arms, including 2
      aminoethylene, 4-aminobutylene, and 6-aminohexylene groups. Cationic amphiphilic
      random copolymers with ethyl methacrylate (EMA) comonomer were prepared with a
      range of comonomer fractions, and the library of copolymers was screened for
      antimicrobial and hemolytic activities. Copolymers with 4-aminobutylene cationic
      side chains showed an order of magnitude enhancement in their antimicrobial
      activity relative to those with 2-aminoethylene spacer arms, without causing
      adverse hemolysis. When the spacer arms were further elongated to hexylene, the
      copolymers displayed potent antimicrobial and hemolytic activities. The 4
      aminobutylene side chain appears to be the optimal spacer arm length for maximal
      antimicrobial potency and minimal hemolysis, when combined with hydrophobic
      ethylmethacrylate in a roughly 70/30 ratio. The copolymers displayed relatively
      rapid bactericidal kinetics and broad-spectrum activity against a panel of Gram
      positive and Gram-negative bacteria. The effect of the spacer arms on the polymer
      conformation in the membrane-bound state was investigated by molecular dynamics
      simulations. The polymer backbones adopt an extended chain conformation, parallel
      to the membrane surface. A facially amphiphilic conformation at the membrane
      surface was observed, with the primary ammonium groups localized at the lipid
      phoshophate region and the nonpolar side chains of EMA comonomers buried in the
      hydrophobic membrane environment. This study demonstrates that the antimicrobial
      activity and molecular conformation of amphiphilic methacrylate random copolymers
      can be modulated by adjustment of cationic side chain spacer arms.

PMID- 22475326
TI  - Climate variations and salmonellosis in northwest Russia: a time-series analysis.
AB  - Associations between monthly counts of all laboratory-confirmed cases of
      salmonellosis in Arkhangelsk, northern Russia, from 1992 to 2008 and climatic
      variables with lags 0-2 were studied by three different models. We observed a
      linear association between the number of cases of salmonellosis and mean monthly
      temperature with a lag of 1 month across the whole range of temperatures. An
      increase of 1  degrees C was associated with a 2.04% [95% confidence interval
      (CI) 0.25-3.84], 1.84% (95% CI 0.06-3.63) and 2.32% (95% CI 0.38-4.27) increase
      in different models. Only one of the three models suggested an increase in the
      number of cases, by 0.24% (95% CI 0.02-0.46) with an increase in precipitation by
      1 mm in the same month. Higher temperatures were associated with higher monthly
      counts of salmonellosis while the association with precipitation was less
      certain. The results may have implications for the future patterns of enteric
      infections in northern areas related to climate change.

PMID- 22475327
TI  - How to predict the timing of eruption of mandibular second premolars.
AB  - OBJECTIVE: To evaluate the relationship between the stages of dental formation
      and the timing of eruption of mandibular second premolars. MATERIALS AND METHODS:
      The sample comprised panoramic radiographs of 25 children, 7 to 12 years old,
      observed by space supervision during development of dentition. The initial
      radiograph (T1) was taken in the mixed dentition period and the progress
      radiograph (T2) close to the eruption of mandibular second premolars. The stages
      of dental formation were determined by the proportion between crown length and
      total length (CL/TL) as well by the Simpson and Kunos index. Average values
      between right and left sides (35, 45) were correlated to the time elapsed until
      dental eruption (T2-T1). Statistical analysis was performed by Pearson
      correlation analysis. RESULTS: The proportion CL/TL presented higher correlation
      index with time to eruption than the Simpson and Kunos index. The linear
      regression equation for prediction of timing of eruption showed high coefficient
      of determination, low deviation, and good accuracy. According to survival
      analysis, mean deviation at 95% confidence level was between 3.6 and 6.4 months.
      There was no difference in contralateral measurements, with high intraclass
      correlation coefficient for both CL/TL proportion and Simpson and Kunos index.
      CONCLUSIONS: More advanced stages of dental formation indicate less time until
      dental eruption. The strong correlation with crown length/total length proportion
      (CL/TL) provides a linear regression equation for prediction of the timing of
      eruption of mandibular second premolars.

PMID- 22475328
TI  - U.S. tabloid magazine coverage of a celebrity dating abuse incident: Rihanna and
      Chris Brown.
AB  - Dating abuse is a prevalent adolescent health problem with substantial public
      health consequences. As many as 1 in 10 high school students in the United States
      reports being "hit, slapped, or physically hurt on purpose" by his or her
      boyfriend or girlfriend in the past year. The authors used the Rihanna-Chris
      Brown dating abuse incident of 2009 as a case study to conduct what is, to our
      knowledge, the first assessment of media framing of dating abuse. The authors
      reviewed the 20 leading U.S. single-copy sales magazines published from February
      to April 2009 and identified 48 relevant articles, which were all printed in 7
      tabloid magazines. The authors conducted a content analysis of the media frames
      of the articles using 5 frame categories: (a) abuse is objectionable, (b) victim
      blaming, (c) abuse is sexualized/romanticized, (d) myths about abuse
      perpetration, and (e) abuse is normalized. Abuse is objectionable was the
      dominant frame of 40% of articles, victim-blaming in 36%. Although the majority
      of articles reviewed (83%) made at least passing reference to the idea that abuse
      is wrong, a minority (40%) used a dominant frame that condemned abuse. Instead,
      the majority of articles communicated mixed messages about dating abuse, and many
      minimized the seriousness of partner abuse perpetration. Advocacy is needed to
      improve future tabloid media framing of dating abuse incidents.

PMID- 22475329
TI  - Foetal echocardiographic assessment of borderline small left ventricles can
      predict the need for postnatal intervention.
AB  - BACKGROUND: We sought to prospectively determine foetal echocardiographic factors
      associated with neonatal interventions in borderline hypoplastic left ventricles.
      METHODS: Foetuses were included who had a left ventricle that was 2-4 standard
      deviations below normal for length or diameter and had forward flow across the
      mitral and aortic valves. Factors associated with an intervention in the first
      month of life or no need for intervention were sought using univariate and
      multivariate logistic regression models. RESULTS: From 2005 to 2008, 47 foetuses
      meeting the criteria had an additional diagnosis (+foetal coarctation/+transverse
      arch hypoplasia): atrioventricular septal defect 7 (+2/+0), double outlet right
      ventricle 2 (+0/+0), Shone's complex 19 (+9/+4), and ventricular disproportion 19
      (+13/+11; 4 both). There were seven pregnancies terminated, three foetal demises,
      and five had compassionate care. There were 32 livebirths that either had a
      biventricular repair (n = 20, n = 2 dead), univentricular palliation (n = 2, both
      alive), or no intervention (n = 9). Overall survival of livebirths to 6 months of
      age was 79%. Factors associated with early intervention on first foetal
      echocardiogram were: obstructed or retrograde arch flow (p = 0.08, odds ratio
      3.3), coarctation (p = 0.05, odds ratio 11.4), and left ventricle outflow
      obstruction (p = 0.05, odds ratio 12.5). Neonatal factors included: Shone's
      diagnosis (p = 0.02, odds ratio 4.9), bicuspid aortic valve (p = 0.005, odds
      ratio 11.7), and larger tricuspid valve z-score (p = 0.05, odds ratio 3.6). A
      neonatal factor associated with no intervention was a larger mitral valve z-score
      (mean 23.8 versus 24.2 intervention group, p = 0.04, odds ratio 2.8). DISCUSSION:
      The need for early intervention in foetuses with borderline hypoplastic left
      ventricle can be predicted by foetal echocardiography.

PMID- 22475330
TI  - Crystals and crystallization in oil-in-water emulsions: implications for emulsion
      based delivery systems.
AB  - Many bioactive components intended for oral ingestion (pharmaceuticals and
      nutraceuticals) are hydrophobic molecules with low water-solubilities and high
      melting points, which poses considerable challenges to the formulation of oral
      delivery systems. Oil-in-water emulsions are often suitable vehicles for the
      encapsulation and delivery of this type of bioactive component. The bioactive
      component is usually dissolved in a carrier lipid phase by either dilution and/or
      heating prior to homogenization, and then the carrier lipid and water phases are
      homogenized to form an emulsion consisting of small oil droplets dispersed in
      water. The successful development of this kind of emulsion-based delivery system
      depends on a good understanding of the influence of crystals on the formation,
      stability, and properties of emulsions. This review article addresses the
      physicochemical phenomena associated with the encapsulation, retention,
      crystallization, release, and absorption of hydrophobic bioactive components
      within emulsions. This knowledge will be useful for the rational formulation of
      effective emulsion-based delivery systems for oral delivery of crystalline
      hydrophobic bioactive components in the food, health care, and pharmaceutical
      industries.

PMID- 22475331
TI  - The role of ABC and SLC transporters in the pharmacokinetics of dietary and
      herbal phytochemicals and their interactions with xenobiotics.
AB  - There is accumulating evidence that many compounds, known as phytochemicals
      (PCs), which are derived from dietary plants and herbs, may have a role in
      combating a number of chronic diseases. Despite many in vitro studies elucidating
      the mechanism(s) of action of various PCs, there are still reservations with
      regard to their health benefits in vivo, particularly as there is a paucity of
      research on their oral bioavailability, their pharmacokinetics, and the
      concentrations achieved at their site(s) of action. Recently various
      transporters, including the ATP-binding cassette (ABC) and the solute carrier
      (SLC) transporters, have been cloned and functional analyses have suggested that
      they play significant roles in the absorption and disposition of most drugs and
      PCs. While some SLC transporters facilitate absorption of PCs into the systemic
      circulation, various efflux pumps, including the ABC transporters, actively
      transport the PC back into the gastro-intestinal (GI) lumen, thus preventing
      further penetration into the body. Some ABC transporters also act in concert with
      Phase 1 and 2 metabolizing enzymes as a defensive barrier in the intestines and
      liver. If the PC overcomes the defence mechanisms of the gut and the liver, it
      will enter the systemic circulation and be distributed to the other organs of the
      body and possible site(s) of action. PCs can usually pass with ease through the
      pores of the capillaries of organs such as the heart and lungs, but with
      difficulty into pharmacological sanctuaries, such as the brain, testis, or
      foetus. Such sanctuaries contain a number of efflux transporters in their
      protective membrane, which restrict the penetration of xenobiotics, including
      PCs. The ABC and SLC transporters are also abundantly expressed in the liver and
      kidney and regulate the excretion of many compounds, including PCs and their
      metabolites. It is also becoming apparent that there is a complex interplay
      between various PCs and their ability to modulate the activity of these
      transporters involved in the processes of absorption, metabolism, distribution
      and excretion, which control the extent of xenobiotic exposure in the body. This
      review describes the importance of the ABC and SLC transporters in the
      pharmacokinetics of dietary and herbal PCs, and their interactions with other
      xenobiotics.

PMID- 22475332
TI  - Roles of UDP-glucuronosyltransferases in phytochemical metabolism of herbal
      medicines and the associated herb-drug interactions.
AB  - UDP-glucuronosyltransferases (UGTs) play important roles in the disposition of
      many drugs and xenobiotics. Herbal medicine, an important group of multicomponent
      therapeutics, is widely and increasingly used. Drug metabolism of herbal medicine
      mediated by cytochrome P450s has been extensively studied; however, herbal
      medicine metabolism mediated by UGTs has not been adequately investigated. Thus,
      it is necessary to evaluate current evidence on the glucuronidation of herbal
      medicines by UGTs. In this review, the research advances of the potential for
      commonly used herbal medicines as UGT substrate and modulator are summarized. In
      addition, the herb-drug interactions associated with UGTs are also discussed.

PMID- 22475333
TI  - Interactions between phytochemicals from traditional Chinese medicines and human
      cytochrome P450 enzymes.
AB  - Traditional Chinese medicine (TCM) formulas with fixed combinations rely on
      "sovereign, minister, assistant and guide" and fuzzy mathematical quantitative
      law, leading to greater challenges for the identification of active ingredients.
      Transformation and metabolic studies involving the Phase I drug-metabolizing
      enzyme cytochrome P450 (CYP) might potentially solve some of these challenges.
      The pharmacological effects can not be attributed to one active ingredient in
      TCMs, but integrated effects resulting from the combined actions of multiple
      ingredients. However, it is only after long-term administration that most
      ingredients exert their actions, which can result in prolonged exposure to herbs
      in vivo. Therefore, interactions between herbal compounds and CYPs appear to be
      inevitable. Yet unlike Western drugs, experimental determination of the
      absorption and disposition properties is not commonly carried out for TCMs.
      Moreover, the use of TCM as injections is an innovation aimed to improve
      efficiency in extensive clinical use in Mainland China. Therefore, in recent
      years, cases of adverse drug reactions (ADR) mainly concerning allergic reactions
      involving TCMs such as ShenMai injection and QingKaiLing injection have been
      reported, which have attracted attention with regard to the legal
      responsibilities for TCM approval. The lack of information on the ADME
      characteristics, especially the metabolic stability and interaction potential
      between CYPs and herbs, increases ADR occurrence due to TCMs. In this article, we
      review the most common herbs used in TCM prescriptions and fixed combinations of
      their usable frequency, and summarize the current understanding of the ability of
      phytochemical ingredients to act as substrates, inhibitors or inducers of human
      CYP enzymes, through which the key role of CYP enzymes on the herb disposition
      and toxicity is highlighted. The potential interaction between herbal
      phytochemicals and CYP enzymes dominates the target exposure, which further helps
      to elucidate the herbal pharmacological basis, assess the individual toxic risk
      of herbal remedies and gain mechanistic insight into herb-drug interactions
      (HDIs).

PMID- 22475334
TI  - Drug metabolism and pharmacokinetics of nanodrugs from Chinese medicines and
      natural products.
AB  - Over the past few years, nanoscale Chinese medicine has become one of focuses in
      modern Chinese medicine research. There is an increasing need for a more
      systematic study on the basic issues involved in traditional Chinese medicine and
      a more active participation of researchers in the application area of nanoscale
      traditional Chinese drugs. In this review, author analyzed the current
      applications of nanotechnology in research and development of drugs from natural
      products and herbal medicines involving traditional Chinese medicines, and also
      discussed the bio-medicinal evaluation issues on ADME including bio-distribution
      and metabolism of nanodrugs. Author noted that great challenges faced in
      nanodrugs from herb drugs and natural products are the follows: (1) the first
      challenge is to prepare nanodrug delivery system and quantitatively evaluate the
      therapeutic effects and safety; (2) the second challenge is to clarify the
      concrete metabolism course; and (3) the third challenge is to study the
      pharmacokinetics of nanodrugs.

PMID- 22475335
TI  - Pharmacokinetics-pharmacology disconnection of herbal medicines and its potential
      solutions with cellular pharmacokinetic-pharmacodynamic strategy.
AB  - Recently, there is a global trend of using herbal medicines to treat various
      chronic diseases and promote health. But the controversy over the safety and
      efficacy of herbal medicines is a focus of attention, primarily because of the
      many unknown and unrevealed natures of herbal medicines, which strongly restricts
      their application and development. Pharmacokinetics is a bridge linking the
      herbal medicines and their pharmacological responses. It is assumed in
      traditional pharmacokinetics that an excellent drug should have appropriate
      pharmacokinetic behaviours and its pharmacological effect is related with plasma
      drug concentrations. However, most herbal medicines exhibit excellent
      pharmacological responses despite poor pharmacokinetic behaviours. As most drugs
      are intracellulartargeted, we put forward cellular pharmacokinetic
      pharmacodynamic strategy, which is focused on the intracellular fate of drugs.
      This strategy could partially explain the marked pharmacological activities of
      herbal medicines from their intracellular pharmacokinetic behaviours, rather than
      their plasma concentrations. It is a helpful complementarity to traditional
      pharmacokinetics, and takes a potential role in the research and development of
      new herb-origined drugs. In this review, the pharmacokinetics-pharmacology
      disconnections of herbal medicines (such as ginseng, berberine and danshen) are
      retrospected. Then our proposed cellular pharmacokineticpharmacodynamic strategy,
      its characteristics, as well as its research procedures are described, followed
      by the subcellular distributions of drug transporters and metabolic enzymes which
      are the determinants of cellular pharmacokinetics-pharmacodynamics. Finally, our
      successful applications of cellular pharmacokinetic-pharmacodynamic strategy in
      elucidating ginsenoside Rh2 as an adjuvant agent and tanshinone IIA as an
      anticancer agent are illustrated.

PMID- 22475336
TI  - The physical chemistry of mass-independent isotope effects and their observation
      in nature.
AB  - Historically, the physical chemistry of isotope effects and precise measurements
      in samples from nature have provided information on processes that could not have
      been obtained otherwise. With the discovery of a mass-independent isotopic
      fractionation during the formation of ozone, a new physical chemical basis for
      isotope effects required development. Combined theoretical and experimental
      developments have broadened this understanding and extended the range of chemical
      systems where these unique effects occur. Simultaneously, the application of mass
      independent isotopic measurements to an extensive range of both terrestrial and
      extraterrestrial systems has furthered the understanding of events such as solar
      system origin and evolution and planetary atmospheric chemistry, present and
      past.

PMID- 22475337
TI  - Computational studies of pressure, temperature, and surface effects on the
      structure and thermodynamics of confined water.
AB  - The behavior of water confined on nanometer length scales is important in a
      diverse set of technical and scientific contexts, ranging from the performance of
      fuel cells and biological molecular machines to the design of self-assembling
      nanoscale materials. Here, we review recent insights into the structure and
      thermodynamics of confined water that have been elucidated primarily by computer
      simulation studies. We emphasize investigations in which interfacial chemistry
      and molecular topography are varied systematically and in which a wide range of
      thermodynamic conditions of temperature and pressure are explored. We consider
      homogeneous interfaces ranging from the simplest hard wall to chemically
      realistic, but structurally ideal, hydrophobic and hydrophilic surfaces, and the
      continuous scale of surface polarity is investigated. Features associated with
      interface heterogeneities arising from chemical patterning or from the natural
      characteristics of protein surfaces are discussed. Finally, we provide our
      thoughts on important directions for further studies.

PMID- 22475338
TI  - Role of conical intersections in molecular spectroscopy and photoinduced chemical
      dynamics.
AB  - This review describes how conical intersections affect measured molecular spectra
      and simple photofragmentation processes. We consider excitations that result in
      electron ejection, that is, photoionization or photodetachment, as well as
      photoinduced H-atom elimination. Section 1 presents a brief overview of the
      history of conical intersections and their rise from an arcane theoretical
      concept to a major paradigm in nonadiabatic chemistry. In Section 2, the generic
      properties of conical intersections are discussed, as well as their
      characterization with modern electronic-structure methods. Section 3 briefly
      discusses computational tools used to compute the nuclear motion involving
      conical intersections. Section 4 describes how the ideas of Sections 2 and 3 are
      combined to simulate molecular spectra impacted by conical intersections. Section
      5 describes selected recent experimental and computational studies of
      photoelectron, photodetachment, and photofragment spectra. Rather than providing
      an encyclopedic bibliography of the previous and current literature, we
      illustrate significant problems currently being addressed and describe what can
      be accomplished with current computational techniques and how these results are
      achieved. Section 6 suggests future directions in this field.

PMID- 22475339
TI  - Advanced nanoemulsions.
AB  - Recent advances in the growing field of nanoemulsions are opening up new
      applications in many areas such as pharmaceuticals, foods, and cosmetics.
      Moreover, highly controlled nanoemulsions can also serve as excellent model
      systems for investigating basic scientific questions about soft matter. Here, we
      highlight some of the most recent developments in nanoemulsions, focusing on
      methods of formation, surface modification, material properties, and
      characterization. These developments provide insight into the substantial
      advantages that nanoemulsions can offer over their microscale emulsion
      counterparts.

PMID- 22475340
TI  - Acute tubulointerstitial nephritis complicating Legionnaires' disease: a case
      report.
AB  - INTRODUCTION: Legionnaires' disease is recognized as a multi-systemic illness.
      Afflicted patients may have pulmonary, renal, gastrointestinal tract and central
      nervous system complications. However, renal insufficiency is uncommon. The
      spectrum of renal involvement may range from a mild and transient elevation of
      serum creatinine levels to anuric renal failure requiring dialysis and may be
      linked to several causes. In our present case report, we would like to draw
      attention to the importance of the pathological documentation of acute renal
      failure by reporting a case of a patient with acute tubulointerstitial nephritis
      complicating Legionnaires' disease. CASE PRESENTATION: A 55-year-old Caucasian
      man was admitted to our hospital for community-acquired pneumonia complicated by
      acute renal failure. Legionella pneumophila serogroup type 1 was diagnosed.
      Although the patient's respiratory illness responded to intravenous erythromycin
      and ofloxacin therapy, his renal failure worsened, he became anuric, and
      hemodialysis was started. A renal biopsy was performed, which revealed severe
      tubulointerstitial nephritis. After initiation of steroid therapy, his renal
      function improved dramatically. CONCLUSIONS: This case highlights the importance
      of kidney biopsies in cases where acute renal failure is a complicating factor in
      Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can
      be confirmed, it will likely respond favorably to steroidal treatment and thus
      irreversible renal damage and chronic renal failure will be avoided.

PMID- 22475341
TI  - Seven billion and 31 gigatons.

PMID- 22475342
TI  - Socio-demographic and lifestyle determinants of 'Western-like' and 'Health
      conscious' dietary patterns in toddlers.
AB  - Determinants of a child's diet shortly after weaning and lactation have been
      relatively understudied. The aim of the present study was hence to identify
      common dietary patterns in toddlers and to explore parental and child indicators
      of these dietary patterns. The study was a population-based, prospective birth
      cohort study in Rotterdam, the Netherlands. Food consumption data of 2420
      children aged 14 months were used. A 'Health conscious' dietary pattern
      characterised by pasta, fruits, vegetables, oils, legumes and fish, and a
      'Western-like' dietary pattern characterised by snacks, animal fats,
      confectionery and sugar-containing beverages were extracted using principal
      component analysis. Low paternal education, low household income, parental
      smoking, multiparity, maternal BMI, maternal carbohydrate intake and television
      watching of child were determinants of a 'Western-like' diet, whereas parental
      age, dietary fibre intake during pregnancy, introduction of solids after 6 months
      and female sex were inversely associated with a 'Western-like' diet of the child.
      Maternal co-morbidity, alcohol consumption during pregnancy and female sex were
      inversely associated with a 'Health conscious' dietary pattern of the child,
      while single parenthood, folic acid use and dietary fibre intake during pregnancy
      were positively associated. All aforementioned associations were statistically
      significant. In conclusion, both 'Western-like' and 'Health conscious' diets can
      already be identified in toddlers. Particularly, adherence to a 'Western-like'
      diet is associated with unfavourable lifestyle factors of the parents and child,
      and low socio-economic background. These findings can form a basis for future
      epidemiological studies regarding dietary patterns and health outcomes in young
      children.

PMID- 22475343
TI  - DNA damage response in imatinib resistant chronic myeloid leukemia K562 cells.
AB  - Resistance to imatinib in patients with chronic myeloid leukemia can lead to
      advanced disease and blast crisis. Conventional chemotherapy with DNA damaging
      agents is then used, alone or in combination with other tyrosine kinase
      inhibitors (TKIs). Our aim was to assess whether imatinib resistant K562 cells
      were also resistant to DNA damaging agents. After treatment with H(2)O(2) and
      doxorubicin, but not camptothecin, cell survival was higher in imatinib resistant
      cells compared to parental cells. DNA damage, measured by comet and gamma-H2AX
      assays, was lower in imatinib resistant cells. mRNA expression levels of 50 genes
      of the DNA damage response pathway showed increased expression of the base
      excision repair (BER) genes MBD4 and NTHL1. Knockdown of MBD4 and NTHL1
      expression in resistant cells using siRNA decreased cell survival after treatment
      with H(2)O(2) and doxorubicin. Our results indicate that imatinib resistant cells
      display cross-resistance to oxidative agents, partly through up-regulation of BER
      genes. Expression of these genes in imatinib resistant patients was not
      significantly different compared to sensitive patients. However, the strategy
      followed in this study could help identify chemotherapeutic agents that are more
      effective as alternative agents in cases of resistance to TKIs.

PMID- 22475344
TI  - An improved method for the synthesis of F-BODIPYs from dipyrrins and
      bis(dipyrrin)s.
AB  - An improved methodology for the synthesis of F-BODIPYs from dipyrrins and
      bis(dipyrrin)s is reported. This strategy employs lithium salts of dipyrrins as
      intermediates that are then treated with only 1 equiv of boron trifluoride
      diethyletherate to obtain the corresponding F-BODIPYs. This scalable route to F
      BODIPYs renders high yields with a facile purification process involving merely
      filtration of the reaction mixture through Celite in many cases.

PMID- 22475345
TI  - Molecular distribution and stable carbon isotopic composition of dicarboxylic
      acids, ketocarboxylic acids, and alpha-dicarbonyls in size-resolved atmospheric
      particles from Xi'an City, China.
AB  - Size-resolved airborne particles (9-stages) in urban Xi'an, China, during summer
      and winter were measured for molecular distributions and stable carbon isotopic
      compositions of dicarboxylic acids, ketocarboxylic acids, and alpha-dicarbonyls.
      To our best knowledge, we report for the first time the size-resolved differences
      in stable carbon isotopic compositions of diacids and related compounds in
      continental organic aerosols. High ambient concentrations of terephthalic (tPh,
      379 +/- 200 ng m(-3)) and glyoxylic acids (omegaC(2), 235 +/- 134 ng m(-3)) in
      Xi'an aerosols during winter compared to those in other Chinese cities suggest
      significant emissions from plastic waste burning and coal combustions. Most of
      the target compounds are enriched in the fine mode (<2.1 MUm) in both seasons
      peaking at 0.7-2.1 MUm. However, summertime concentrations of malonic (C(3)),
      succinic (C(4)), azelaic (C(9)), phthalic (Ph), pyruvic (Pyr), 4-oxobutanoic
      (omegaC(4)), and 9-oxononanoic (omegaC(9)) acids, and glyoxal (Gly) in the coarse
      mode (>2.1 MUm) are comparable to and even higher than those in the fine mode
      (<2.1 MUm). Stable carbon isotopic compositions of the major organics are higher
      in winter than in summer, except oxalic acid (C(2)), omegaC(4), and Ph.
      delta(13)C of C(2) showed a clear difference in sizes during summer, with higher
      values in fine mode (ranging from -22.80/00 to -21.90/00) and lower values in
      coarse mode (-27.10/00 to -23.60/00). The lower delta(13)C of C(2) in coarse
      particles indicate that coarse mode of the compound originates from evaporation
      from fine mode and subsequent condensation/adsorption onto pre-existing coarse
      particles. Positive linear correlations of C(2), sulfate and omegaC(2) and their
      delta(13)C values suggest that omegaC(2) is a key intermediate, which is formed
      in aqueous-phase via photooxidation of precursors (e.g., Gly and Pyr), followed
      by a further oxidation to produce C(2).

PMID- 22475346
TI  - Heightened expression of MICA enhances the cytotoxicity of NK cells or CD8+T
      cells to human corneal epithelium in vitro.
AB  - BACKGROUND: Major-histocompatibility-complex class I-related chain A (MICA)
      antigens are the ligands of NKG2D, which is an activating or coactivating
      receptor expressed on human NK cells and CD8+T cells. We sought to determine
      whether MICA expression in human corneal epithelium (HCE) could affect the
      cytotoxicity mediated by NK cells or CD8+T cells. METHODS: Cell cultures of HCE
      were harvested from human donor eyes. Flow cytometric analysis and ELISA was
      performed to determine the levels of MICA expression on HCE. Then, HCE was
      transfected with a lentivirus vector expressing MICA and GFP. Flow cytometric
      analysis, RT-PCR, western blot and ELISA were performed to check the levels of
      MICA expression. For cytotoxicity testing, allogeneic NK cells and CD8+T cells
      were isolated from peripheral blood mononuclear cells of healthy volunteers by
      magnetic cell sorting. The cytolytic activity of NK cells and CD8+T cells was
      assessed against MICA-transfected HCE (NK cells: E:T ratio = 3:1; CD8+T cells:
      E:T ratio = 10:1) using the nonradioactive cytotoxicity detection kit lactate
      deshydrogenase. RESULTS: Surface expression of MICA on corneal epithelium was
      identified at a low level. A cell line of stable human MICA-transfected corneal
      epithelium was successfully established. Heightened expression of MICA on HCE was
      found to promote the cytotoxicity mediated by NK cells or CD8+T cells, which
      could be blocked by an anti-MICA antibody. CONCLUSION: MICA molecules may
      contribute to cytotoxic responses mediated by activated immune effector cells in
      corneal epithelium immunity.

PMID- 22475347
TI  - Selective chemical imaging of static actin in live cells.
AB  - We have characterized rationally designed and optimized analogues of the actin
      stabilizing natural products jasplakinolide and chondramide C. Efficient actin
      staining was achieved in fixed permeabilized and non-permeabilized cells using
      different combinations of dye and linker length, thus highlighting the degree of
      molecular flexibility of the natural product scaffold. Investigations into
      synthetically accessible, non-toxic analogues have led to the characterization of
      a powerful cell-permeable probe to selectively image static, long-lived actin
      filaments against dynamic F-actin and monomeric G-actin populations in live
      cells, with negligible disruption of rapid actin dynamics.

PMID- 22475348
TI  - Early activation of myocardial matrix metalloproteinases and degradation of
      cardiac troponin I after experimental subarachnoid hemorrhage.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are involved in acute myocardial
      dysfunction by degrading several intracellular contractile proteins, including
      cardiac troponin I (cTnI). Here, we examined the temporal profiles of MMPs and
      cTnI in plasma and myocardial tissue in the acute stage of subarachnoid
      hemorrhage (SAH). MATERIALS AND METHODS: SAH was induced by the endovascular
      suture method in rats. Intracranial pressure and left ventricular (LV) function
      were recorded. Plasma cTnI and MMPs were measured at 0, 5, 15, 30, 60, 120, and
      180 minutes after SAH. Myocardial cTnI and MMP activities were quantified at 30,
      60 and 180 min after SAH from homogenized hearts. RESULTS: SAH-induced rats
      showed a marked decline in -LV dP/dt(max) (index of LV diastolic function).
      Plasma samples revealed a noticeable increase in cTnI and pro-MMP-9 activities
      over the course of 180 minutes. In myocardial tissue, there was a marked increase
      in pro-MMP-9, pro-MMP-2 activities and expression of activated MMP-2. Western
      blot analysis revealed a striking decrease in cTnI content and increase in cTnI
      degradation in myocardium. Simultaneous cTnI depletion and MMP-2 expression in
      myocardium was detected by immunohistochemistry as early as 30 minutes after SAH.
      MMPs correlated with -LV dP/dt(max) (% of baseline) both in plasma and in
      myocardial tissue. Furthermore, activated MMP-2 activity correlated positively
      with cTnI degradation in myocardium. CONCLUSIONS: Early activation of MMPs was
      observed in myocardium and plasma following SAH. Activated MMP-2 may regulate
      proteolytic cTnI and contribute to myocardium stunning injury in SAH rats.

PMID- 22475349
TI  - Protective effects of hydrogen-rich saline in a rat model of traumatic brain
      injury via reducing oxidative stress.
AB  - BACKGROUND: Hydrogen gas (H(2)) has been considered as a novel antioxidant to
      selectively reduce the toxic reactive oxygen species (ROS) such as hydroxyl
      radical (*OH) without affecting the other signal ROS. Our recent study shows that
      H(2) inhalation is beneficial to traumatic brain injury (TBI) via reducing
      oxidative stress. In contrast to H(2), hydrogen-rich saline (HS) may be more
      suitable for clinical application. The present study was designed to investigate
      whether HS has a protective effect against TBI via reducing oxidative stress in
      rats. METHODS: TBI model was induced by controlled cortical impact injury.
      Different dosages of HS were intraperitoneally administered at 5 min after TBI
      operation. We then measured the brain edema, blood-brain barrier (BBB) breakdown,
      neurological dysfunction and injury volume in all animals. In addition, the
      oxidative products and antioxidant enzymes in brain tissues were detected.
      RESULTS: TBI-challenged rats exhibited significant brain injuries characterized
      by the increase of BBB permeability, brain edema, and lesion volume as well as
      neurological dysfunction, which were dose-dependently ameliorated by HS
      treatment. Moreover, we found that HS treatment increased the endogenous
      antioxidant enzymatic activities and decreased the oxidative product levels in
      brain tissues of TBI-challenged rats. CONCLUSION: Hydrogen-rich saline can exert
      a protective effect against TBI via reducing oxidative stress. Molecular hydrogen
      may be a more effective therapeutic strategy for TBI patients.

PMID- 22475350
TI  - Localization of mesenchymal stem cells grafted with a hyaluronan-based scaffold
      in the infarcted heart.
AB  - BACKGROUND: Permanence of grafted stem cells in the infarcted myocardial area has
      been suggested to be favored by tissue engineering strategies, including the
      application of a scaffold as a cell support. However, an estimation of how many
      cells remain localized in the site of transplantation has never been done. The
      aim of this work was to investigate the localization of mesenchymal stem cells
      (MSCs) grafted with a well cell-adhesive polymer in the scar region of the
      infarcted heart. MATERIALS AND METHODS: Rat MSCs were engineered in a hyaluronan
      based scaffold (HYAFF((r))11) for 3 wk. The hearts of donor rats were also
      explanted, subjected to coronary artery ligation, and grafted into the abdomen of
      syngeneic rats. Two wk after coronary ligation a small dish of the
      HYAFF((r))11/MSC construct was introduced into a pouch created in the ventricular
      wall of the infarct area and left for 2 wk. RESULTS: Under ex vivo conditions,
      MSCs tightly adhered to the hyaluronan fibers and secreted abundant extracellular
      matrix. In contrast, HYAFF((r))11 was not more surrounded by the engrafted MSCs 2
      wk after construct transplantation. Most MSCs migrated near the border zone of
      the infarcted area close to the coronary vessels. Moreover, the infarcted region
      of the heart was enriched in capillaries and the degree of fibrosis was
      attenuated. CONCLUSIONS: Two wk after transplantation most MSCs grafted in the
      infarcted myocardium with HYAFF((r))11 had left the scaffold and moved to the
      border zone. Nevertheless, this treatment increased the myocardial
      vascularization and reduced the degree of fibrosis in the scar area.

PMID- 22475351
TI  - Tetrahydrobiopterin ameliorates hepatic ischemia-reperfusion Injury by coupling
      with eNOS in mice.
AB  - BACKGROUND: In the liver, eNOS appears to have a central role in protecting
      against ischemia/reperfusion (I/R) injury. We hypothesized that
      tetrahydrobiopterin (BH4) would protect livers subjected to I/R injury by
      coupling with eNOS. METHODS: Chinese Kun Ming (KM) mice were subjected to 60 min
      of 70% hepatic ischemia 30 min after the administration of BH4 or saline. After
      reperfusion, survival was evaluated. The histologic appearance and ALT, BH4,
      nitrite/nitrate, 8-isoprostane, and eNOS protein expression levels were measured.
      RESULTS: The 1-wk survival rate was 66.67% in the BH4 group and 33.33% in the
      saline group. The serum ALT values in the BH4 group 1, 3, 6, 12, and 24 h after
      reperfusion were significantly lower than those of the saline group. A histologic
      examination of the liver revealed only a small necrotic area in the BH4 group as
      opposed to massive necrosis in the saline group. The percentage values of the
      hepatic necrotic area 24 h after reperfusion were significantly less for the BH4
      group than for the saline group. The nitrite/nitrate levels in the liver tissue
      were significantly increased by ~2-fold in the BH4 group compared with the saline
      group. The free radical indicator 8-isoprostane was reduced approximately 50% in
      the BH4 group compared with the saline group. Western blotting showed that the
      level of eNOS protein between the groups was not significantly different.
      CONCLUSIONS: BH4 significantly improved the survival rate by reducing liver
      failure. This was supported by the histologic findings, and the mechanism was
      explored. According to the results, we suggest that BH4 prevents liver damage
      from I/R injury by attenuating reactive oxygen species and increasing NO
      synthesis, and might provide a novel and promising therapeutic option for
      preventing I/R injury.

PMID- 22475352
TI  - Effect of hypertonic saline on apoptosis of polymorphonuclear cells.
AB  - BACKGROUND: The function of polymorphonuclear (PMN) cells can be influenced by
      the choice of resuscitation fluids in hemorrhagic shock. Widespread interest in
      the use of hypertonic solutions for resuscitation has led to extensive
      investigation of their immune-modulating properties. Hypertonic saline (HTS) is
      known to modulate immune reactions, preventing the multiorgan failure mediated by
      immune reactions in trauma and hemorrhagic shock. PMN cells play a key role in
      such immune-mediated inflammatory processes, and HTS is believed to affect these
      PMN cells. However, how these events influence the actual event of apoptosis has
      not yet been described. Thus, in the present study, we aimed to investigate the
      differences in the apoptosis of PMN cells when exposed to isotonic and hypertonic
      environments and the temporal relations between the interval of administration of
      HTS after the stimulation of PMN cells. METHODS: Whole blood was sampled from
      healthy volunteers, and the PMN cells were isolated. The isolated layer of PMN
      cells was washed twice with phosphate-buffered saline to yield the PMN cells. The
      number of cells was kept uniform, and an overall survival rate greater than 95%
      was maintained. After stimulation of the isolated PMN cells with N-formyl
      methionyl-leucyl-phenylalanine, the PMN cells were allocated into 3 study groups
      (i.e., 1 isotonic group and 2 hypertonic groups with an osmolarity of 160 mM and
      180 mM each). The extent of apoptosis was investigated in each group after
      culturing the PMN cells for 0, 1, 3, 6, 12, 15, 18, and 24 h. Depending on
      whether the PMN cells were stimulated with N-formyl-methionyl-leucyl
      phenylalanine, they were also divided into stimulated and nonstimulated groups.
      In the stimulated group, the hypertonic environment was fostered immediately (HTS
      0 h) and 6 h (HTS 6 h) after stimulation, which was accomplished after allocating
      the cells into an isotonic group (140 mM) and a hypertonic group (180 mM),
      according to the concentration of the culture medium. The PMN cells were then
      cultured at 37 degrees C for 15 h with 5% carbon dioxide incubation. Each PMN
      suspension was labeled with Annexin V-fluorescein isothiocyanate and propidium
      iodide. Each sample underwent immediate flow cytometric analysis. PMN cells with
      high propidium iodide uptake were considered nonviable (necrotic). Among the
      viable PMN cells, those with no Annexin V uptake were considered normal and those
      with Annexin V uptake were considered apoptotic. RESULTS: Decreased apoptosis was
      observed in the PMN cells stimulated with N-formyl-methionyl-leucyl
      phenylalanine. Increased apoptosis was observed in the stimulated PMN cells
      incubated in hypertonic condition compared with the cells incubated in isotonic
      condition. Early HTS administration demonstrated increased apoptosis compared
      with late administration. CONCLUSIONS: HTS treatment resulted in increased PMN
      apoptosis and an anti-inflammatory effect. Decreased apoptosis (prolonged
      lifespan) has been implicated in neutrophil-mediated tissue damage. HTS, by
      increasing the apoptosis of PMN cells, attenuates the postinjury inflammatory
      response. Also, early treatment with HTS was more efficient than delayed
      treatment.

PMID- 22475353
TI  - Creation of rabbit bone and soft tissue tumor using cultured VX2 cells.
AB  - BACKGROUND: To create rabbit VX2 bone tumors, it is surgically less demanding to
      implant VX2 cell suspensions than minced tumor fragments. A VX2 cell line that
      can be expanded using standard cell culture techniques might provide an unlimited
      supply of cells needed to create these bone tumors. Therefore, the aim of the
      present study was to establish a VX2 cell line and verify its tumorigenicity in
      an athymic mouse and rabbit animal model. MATERIALS AND METHODS: Minced VX2 tumor
      fragments were allowed to grow as a monolayer in 10 mL Dulbecco's modified Eagle
      medium/nutrient mixture F-12 (1:1) supplemented with 10% fetal calf serum and
      passaged multiple times. The tumorigenecity of the cultured VX2 cells were tested
      in athymic mice (intradermal tumor development) and in New Zealand white rabbits
      (bone and soft tissue tumor model). RESULTS: The VX2 cells proliferated rapidly
      in tissue culture flasks containing Dulbecco's modified Eagle medium/nutrient
      mixture F-12 medium supplemented with 10% fetal bovine serum. After reaching
      confluence, the VX2 cells can only be subcultured when plated at a greater
      density (e.g., at a dilution of 1:1). All 6 athymic mice developed tumors within
      15 d of VX2 cell suspension implantation. In the rabbits, the VX2 cells were able
      to produce tumors in muscle tissue and in the distal femurs but not in the
      proximal tibia. CONCLUSIONS: VX2 cell lines can be successfully created from VX2
      tumor fragments and passaged multiple times. In contrast to previous reports, the
      VX2 cells grown in vitro are capable of maintaining their tumorigenecity.
      However, successful tumor growth might depend on the initial number of cells
      implanted and the use of extracellular matrices for tumor proliferation.

PMID- 22475355
TI  - Volatile anesthetic preconditioning attenuated sepsis induced lung inflammation.
AB  - BACKGROUND: This study aimed to evaluate the differential protective effects of
      isoflurane or sevoflurane on lung inflammation in a rat model of cecal ligation
      and puncture (CLP) induced sepsis. METHODS: Seventy-two rats were assigned to
      control, sevoflurane, or isoflurane groups. At 2 and 4 h, tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta),
      nitrate/nitrate levels (NO), total antioxidant capacity (TAC), and intercellular
      cell adhesion molecule-1 (ICAM-1) were determined. At 12 and 24 h,
      malondialdehyde (MDA), myeloperoxidase (MPO), and histologic changes were
      evaluated. Survival was monitored for 7 d after CLP. RESULTS: Sevoflurane (75%)
      and isoflurane (63%) significantly improved survival rate compared with control
      rats (38%). When sevoflurane and isoflurane groups were compared, sevoflurane
      pretreatment showed significant decrease in NO at 2 h [1045 (803-1274)/1570 (1174
      2239) and 4 h [817 (499-1171)/1493 (794-2080)]; increase in TAC at 4 h [580.0
      (387-751)/320 (239-512)]; decrease in MDA at 12 h [2.5 (1.1-4.2)/5.4 (4-73)] and
      24 h [10.8 (6.0-14.0)/15.9 (9-28)]; and decrease in MPO at 24 h [145.8 (81
      260)/232 (148-346)]. The difference in the ICAM-1 expression of the isoflurane
      and sevoflurane groups was not significant at both measurement times. The
      architectural integrity of the alveoli was preserved in all the groups. The
      injury scores of the three groups at 12 and 24 h did not show any significant
      difference. CONCLUSIONS: Both sevoflurane and isoflurane attenuated inflammatory
      response, lipid peroxidation, and oxidative stress. Furthermore, sevoflurane was
      more effective in modulating sepsis induced inflammatory response at the chosen
      concentration in sepsis model.

PMID- 22475354
TI  - Physiologic responses to severe hemorrhagic shock and the genesis of
      cardiovascular collapse: can irreversibility be anticipated?
AB  - BACKGROUND: The causes of cardiovascular collapse (CC) during hemorrhagic shock
      (HS) are unknown. We hypothesized that vascular tone loss characterizes CC, and
      that arterial pulse pressure/stroke volume index ratio or vascular tone index
      (VTI) would identify CC. METHODS: Fourteen Yorkshire-Durock pigs were bled to 30
      mmHg mean arterial pressure and held there by repetitive bleeding until rendered
      unable to compensate (CC) or for 90 min (NoCC). They were then resuscitated in
      equal parts to shed volume and observed for 2 h. CC was defined as a MAP < 30
      mmHg for 10 min or <20 mmHg for 10 s. Study variables were recorded at baseline
      (B0), 30, 60, 90 min after bleeding and at resuscitation (R0), 30, and 60 min
      afterward. RESULTS: Swine were bled to 32% +/- 9% of total blood volume.
      Epinephrine (Epi) and VTI were low and did not change in NoCC after bleeding
      compared with CC swine, in which both increased (0.97 +/- 0.22 to 2.57 +/- 1.42
      mcg/dL, and 173 +/- 181 to 939 +/- 474 mmHg/mL, respectively), despite no
      differences in bled volume. Lactate increase rate (LIR) increased with hemorrhage
      and was higher at R0 for CC, but did not vary in NoCC. VTI identified CC from
      NoCC and survivors from non-survivors before CC. A large increase in LIR was
      coincident with VTI decrement before CC occurred. CONCLUSIONS: Vasodilatation
      immediately prior to CC in severe HS occurs at the same time as an increase in
      LIR, suggesting loss of tone as the mechanism causing CC, and energy failure as
      its probable cause.

PMID- 22475356
TI  - Therapeutic assessment with an adolescent: choosing connections over substances.
AB  - This case study provides an in-depth example of a comprehensive therapeutic
      assessment with an adolescent (TA-A) and his parents. The TA-A addressed parental
      concerns about their son's drug experimentation as well as the adolescent's own
      private questions about his distinctiveness from others, all set against a
      backdrop of ongoing parental conflict and poor communication. The TA-A process
      and how it is specifically tailored to balance the needs of adolescents and their
      parents is discussed. Subsequently, each step of TA-A is illustrated through the
      case study. Research findings at the conclusion of the assessment and at follow
      up indicated significant decreases in internalizing symptomology and school
      problems, increases in self-esteem and self-reliance, and improved family
      functioning as reported by the adolescent. At follow-up, the father spoke of
      developing a more assertive parenting approach and successful follow-through on
      recommendations. This case study provides a template for clinicians interested in
      conducting TA-A.

PMID- 22475357
TI  - Sudden blast crisis in chronic myeloid leukemia treated with tyrosine kinase
      inhibitors.

PMID- 22475358
TI  - The persisting burden of visceral leishmaniasis in Iraq: data of the National
      Surveillance System, 1990-2009.
AB  - Visceral leishmaniasis (VL) is an endemic parasitic disease transmitted by the
      bite of sand flies. To describe trends and demographics of reported VL cases, we
      reviewed surveillance data from 1990-2009. Reported VL incidence per 100 000
      population was 2.6 in 2007, 3.1 in 2008, and 4.8 in 2009, mostly in children aged
      <5 years. The number of cases varied greatly in step with prevailing economic and
      security conditions, raising concerns about the completeness and quality of
      surveillance data. Nevertheless, we conclude that VL remains an important endemic
      disease in Iraq and that surveillance system is recovering the capacity to detect
      cases as the country experiences greater stability. We recommend conducting
      formal entomological investigations, and evaluating existing control measures.

PMID- 22475359
TI  - Cytochrome c: potential as a noninvasive biomarker of drug-induced acute kidney
      injury.
AB  - INTRODUCTION: Acute kidney injury (AKI) in critically ill patients is closely
      associated with increased morbidity and mortality, yet there remains continued
      reliance on increased serum creatinine and blood urea nitrogen to diagnose AKI.
      These biomarkers increase only after significant renal structural damage has
      occurred. Recent research efforts have focused on discovery and validation of
      novel serum and urine biomarkers to detect AKI prior to extensive structural
      damage. Cytochrome c is best known as an indicator of cell death burden in any
      organ or tissue. It is released during mitochondrial damage that is associated
      with processing of apoptosis, cell lysis during necrosis and even reversible
      mitochondrial and cell injury. AREAS COVERED: This article reviews the current
      literature on the potential for cytochrome c as an early biomarker of AKI. The
      article is based on PubMed searches, using the terms 'acute kidney injury,'
      'renal failure,' 'biomarker,' 'toxicity' and 'cytochrome c', with a focus on
      experimental and clinical data. EXPERT OPINION: Cytochrome c, as a biomarker, has
      the potential to improve outcome for AKI patients. Its release indicates
      mitochondrial damage, one of the earliest changes in cell injury and death. New
      mitochondrial-targeted therapeutics may be designed around this molecule. Its
      disadvantages include only transient increase at expression levels that are
      easily measurable and nonspecificity for kidney injury. The appropriate and
      optimal utilization of cytochrome c as a biomarker for AKI will be realized only
      after its complete characterization in experimental and clinical arenas.

PMID- 22475360
TI  - A novel titin mutation in adult-onset familial dilated cardiomyopathy.
AB  - Familial dilated cardiomyopathy is a major cause of advanced heart failure and
      heart transplantation. In most families, the disease-causing mutation is unknown,
      and relatives should therefore undergo periodic screening to facilitate early
      diagnosis and therapy. In the present study, we describe a novel titin truncation
      mutation causing adult-onset familial dilated cardiomyopathy in an Israeli Arab
      family. The family members underwent physical examination, electrocardiography,
      and Doppler echocardiography. Linkage to candidate loci was performed, followed
      by gene sequencing. We identified 13 clinically affected family members (8 men
      and 5 women, mean age 47 +/- 12 years). Compared with their healthy first-degree
      relatives, the affected relatives had a larger end-diastolic left ventricular
      dimension (60 +/- 10 vs 49 +/- 4 mm, p <0.001), lower ejection fraction (43 +/-
      11% vs 60 +/- 6%, p <0.001), and markedly higher end-systolic volume indexes but
      no difference in wall thickness or diastolic function. The linkage studies or
      direct sequencing excluded LMNA, MYH7, TNNT2, TNNI3, SCN5A, DES, SGCD, ACTC, PLN,
      and MYH6 but established linkage to the TTN locus at chromosome 2q31, yielding a
      maximum (2-point) LOD score of 3.44. Sequence analysis identified an insertion
      (c.58880insA), causing protein truncation after 19,628 amino acids
      (p.S19628IfsX1). No founder effect was found among the Israeli Arabs. In
      conclusion, titin is a giant protein with a key role in sarcomere assembly, force
      transmission, and maintenance of resting tension. Although some mutations result
      in skeletal myopathy, others cause isolated, maturity-onset cardiomyopathy.

PMID- 22475361
TI  - Echocardiographic evaluation of iatrogenic atrial septal defect after catheter
      based mitral valve clip insertion.
AB  - The geometries and sizes of persistent iatrogenic atrial septal defects (IASDs)
      after transseptal puncture during catheter-based mitral valve clip insertion
      (MVCI) have not been detailed. In this study, 11 IASDs were investigated in 10
      patients who underwent MVCI using a guide catheter (24Fr proximally and 22Fr at
      the atrial septum). The diameters of the long and short axes and the area at
      maximum and minimum during a cardiac cycle were measured after MVCI using real
      time 3-dimensional (RT3D) transesophageal echocardiography (TEE). A circular
      shape was assumed on 2-dimensional TEE, resulting in an area calculation of pi *
      (dimension/2)(2). The anatomic geometries of IASDs were visualized in a 3
      dimensional en face view of the atrial septum. Furthermore, 1 month after MVCI,
      IASDs were evaluated using echocardiography. The IASDs had a variety of irregular
      geometries. The mean long-axis diameter was 1.0 +/- 0.24 cm, the mean short-axis
      diameter was 0.51 +/- 0.22 cm, and the mean area was 0.40 +/- 0.24 cm(2) on RT3D
      TEE. The diameters and area changed significantly between the maximal and minimal
      values during the cardiac cycle. Importantly, 2-dimensional TEE underestimated
      the maximal diameters of IASDs (0.54 +/- 0.17 vs 1.0 +/- 0.24 cm by RT3D TEE, p
      <0.01) and the maximal areas of IASDs (0.25 +/- 0.15 vs 0.40 +/- 0.23 cm(2) by
      RT3D TEE, p <0.05). One month after MVCI, the smallest and the second smallest
      IASDs had closed, and the other 9 remained open. In conclusion, RT3D TEE is
      useful to assess the irregular geometries of IASDs created during MVCI.

PMID- 22475362
TI  - Bleeding-avoidance strategies and outcomes in patients >=80 years of age with ST
      elevation myocardial infarction undergoing primary percutaneous coronary
      intervention (from the NCDR CathPCI Registry).
AB  - The purpose of our study was to evaluate the use of bleeding-avoidance strategies
      (BAS) and risk-adjusted bleeding over time in patients >=80 years of age
      undergoing primary percutaneous coronary intervention (PCI) for ST-segment
      elevation myocardial infarction. We analyzed data from the CathPCI Registry from
      July 1, 2006 through June 30, 2009. Patients were included if they were >=80
      years old, presented with ST-segment elevation myocardial infarction, and
      underwent primary PCI. We evaluated trends in use of BAS (direct thrombin
      inhibitors, vascular closure devices, and radial access) and risk-adjusted
      bleeding over time. Of 10,469 patients >=80 years old undergoing primary PCI,
      1,002, (9.6%) developed a bleeding complication. Use of direct thrombin
      inhibitors and vascular closure devices increased over time (12.8% to 24.9% and
      29.2% to 32.7%, p <0.01 and <0.05 for trends, respectively). Radial access was
      extremely uncommon (<1%) and did not change over the course of the study. In
      multivariable analyses, use of BAS was associated with lower bleeding. However,
      over the course of the study period, overall risk-adjusted bleeding did not
      decrease significantly (9.9% to 9.4%, p = 0.14 for trend). In conclusion,
      patients >=80 years old undergoing primary PCI are at high risk of bleeding, and
      despite significant increases in use of BAS, the overall rate of bleeding
      complications remains high.

PMID- 22475363
TI  - Therapy with the histone deacetylase inhibitor pracinostat for patients with
      myelofibrosis.
AB  - Approximately half of the patients with myelofibrosis (MF) carry mutant
      JAK2(V617F) proteins. JAK2(V617F) has been recently shown to translocate to the
      nucleus and modify specific histones, thus regulating transcription. We report on
      a phase II study testing the activity and tolerability of the histone deacetylase
      inhibitor pracinostat given at 60 mg every other day for three weeks per month in
      22 patients with intermediate or high risk MF. Eight (36%) patients experienced
      clinical benefit, with 6 (27%) experiencing reductions in splenomegaly (median 3
      cm, range 1-4 cm). According to International Working Group criteria, 2 (9%)
      patients had clinical improvement (anemia response in both cases). The most
      frequent side effect associated to pracinostat therapy was fatigue, which
      occurred in 20 (91%) patients (grade 2 in 3 patients). Grade 3-4 neutropenia,
      anemia, and thrombocytopenia occurred in 13%, 0%, and 21%, respectively. Twenty
      one patients permanently discontinued pracinostat, mainly due to lack of
      efficacy. In conclusion, pracinostat at the dose tested is reasonably tolerated
      and has modest activity in patients with MF.

PMID- 22475364
TI  - T-cell large granular lymphocytosis associated with malignant thymoma.

PMID- 22475365
TI  - Combined effect of histone deacetylase inhibitor suberoylanilide hydroxamic acid
      and anti-CD20 monoclonal antibody rituximab on mantle cell lymphoma cells
      apoptosis.
AB  - Interactions between histone deacetylases inhibitor suberoylanilide hydroxamic
      acid (SAHA) and anti-CD20 monoclonal antibody rituximab in mantle cell lymphoma
      have been examined both in vitro and in vivo. The combination of SAHA and
      rituximab synergistically induced apoptosis, concomitant with caspase activation
      and Bcl-2 downregulation. These events were associated with multiple
      perturbations in signal transduction pathways, including inactivation of cyto
      protective nuclear factor (NF)-kappaB, Akt, extracellular signal-regulating
      kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38MAPK) pathways,
      and activation of c-jun N-terminal kinase (JNK) when pretreated with the pan
      caspase inhibitor. Moreover, the combination of SAHA and rituximab significantly
      inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice.
      However, SAHA had no apparent effect on the CD20 expression in the two MCL cell
      lines. Taken together, our results demonstrate the synergistic anti-MCL activity
      of SAHA and rituximab, and build the framework for clinical trials using SAHA
      rituximab combining regimen in the treatment of MCL.

PMID- 22475366
TI  - Up-regulation of interleukin-6 and vascular endothelial growth factor-A in the
      synovial fluid of temporomandibular joints affected by synovial chondromatosis.
AB  - Our aim was to explore important inflammatory mediators for synovial
      chondromatosis in the temporomandibular joints (TMJs) by analysing synovial
      fluid. Samples were collected from 10 patients with unilateral synovial
      chondromatosis of the TMJ. Control samples were obtained from 11 subjects with no
      symptoms in the TMJ. Concentrations of aggrecan, interleukin (IL)-2, IL-4, IL-5,
      IL-6, IL-8 (CXCL8), IL-10, interferon (IFN)-gamma, tumour necrosis factor (TNF)
      alpha and vascular endothelial growth factor (VEGF)-A were measured in the
      samples of synovial fluid, and the results in the two groups compared. The
      tissues from the affected TMJ were examined histologically and
      immunohistochemically. Of the proteins evaluated, the concentrations of aggrecan,
      IL-6, and VEGF-A were significantly higher in the group with synovial
      chondromatosis. The immunohistochemical analysis showed that the synovial cells
      around the osteocartilaginous nodules were vigorously expressing VEGF-A. IL-6 and
      VEGF-A are thought to have important roles in the pathology of synovial
      chondromatosis of the TMJ.

PMID- 22475367
TI  - Minimally-invasive open reduction of intracapsular condylar fractures with
      preoperative simulation using computer-aided design.
AB  - Reduction of intracapsular condylar fractures is difficult, so we have based our
      technique on preoperative simulation using computer-aided design (CAD), which has
      proved useful in other surgical specialties. We have treated 11 patients with
      intracapsular condylar fractures. Before the operation the procedure was shown on
      the computer using a three-dimensional simulation system. The relation between
      the stump and the fragment of the condyle, and assessment of the position and the
      size of the screw, were made preoperatively to obtain a perfect fit. The
      displaced fragment was reduced by elevators, and fixed with a bicortical screw
      through a minimised preauricular incision under general anaesthesia. The
      fragments and the location of the screws were similar on the preoperative
      simulation and on the postoperative computed tomographic (CT) scan. The reduction
      and fixation of the fracture showed a perfect fit on the same view in the
      preoperative CAD simulation in the Mimics 10.01 software and postoperatively.
      Postoperative clinical examinations showed good occlusion and satisfactory mouth
      opening. Two patients had temporary paralysis of the occipitofrontalis muscle
      that recovered within 3 months. All patients regained normal mandibular movements
      and had short and invisible scars at 6 months' follow up. The technique of CAD
      simulation could help to improve the accuracy during open treatment for
      intracapsular condylar fractures.

PMID- 22475368
TI  - Tuberculosis of the temporomandibular joint: part of a bigger picture.

PMID- 22475370
TI  - Best practice guidelines on surgical response in disasters and humanitarian
      emergencies: report of the 2011 Humanitarian Action Summit Working Group on
      Surgical Issues within the Humanitarian Space.
AB  - The provision of surgery within humanitarian crises is complex, requiring
      coordination and cooperation among all stakeholders. During the 2011 Humanitarian
      Action Summit best practice guidelines were proposed to provide greater
      accountability and standardization in surgical humanitarian relief efforts.
      Surgical humanitarian relief planning should occur early and include team
      selection and preparation, appropriate disaster-specific anticipatory planning,
      needs assessment, and an awareness of local resources and limitations of cross
      cultural project management. Accurate medical record keeping and timely follow-up
      is important for a transient surgical population. Integration with local health
      systems is essential and will help facilitate longer term surgical health system
      strengthening.

PMID- 22475371
TI  - Protein restriction in early life is associated with changes in insulin
      sensitivity and pancreatic beta-cell function during pregnancy.
AB  - Malnutrition in early life impairs glucose-stimulated insulin secretion in
      adulthood. Conversely, pregnancy is associated with a significant increase in
      glucose-stimulated insulin secretion under conditions of normoglycaemia. A
      failure in beta-cell adaptive changes may contribute to the onset of diabetes.
      Thus, glucose homeostasis and beta-cell function were evaluated in control-fed
      pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non
      pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats
      that were recovered after weaning (RP and RNP). The typical insulin resistance of
      pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin
      content/islet in the LPP group. The glucose dose-response curves from pregnant
      rats were shifted to the left in relation to the non-pregnant rats, except in the
      recovered group. Glucose utilisation but not oxidation in islets from the RP and
      LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets
      from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated
      insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose
      indicated increased adenylyl cyclase 3 activity but reduced protein kinase A
      alpha activity in islets from the RP and LPP rats. Protein kinase C (PKC)-alpha
      but not phospholipase C (PLC)-beta1 expression was reduced in islets from the RP
      group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of
      glucose-stimulated insulin secretion in the RP group. Thus, the alterations
      exhibited by islets from the LPP group appeared to be due to reduced islet mass
      and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity
      apparently resulted from uncoupling between glucose metabolism and the amplifying
      signals of the secretory process, as well as a severe attenuation of the PLC/PKC
      pathway.

PMID- 22475372
TI  - Hybrid computing: CPU+GPU co-processing and its application to tomographic
      reconstruction.
AB  - Modern computers are equipped with powerful computing engines like multicore
      processors and GPUs. The 3DEM community has rapidly adapted to this scenario and
      many software packages now make use of high performance computing techniques to
      exploit these devices. However, the implementations thus far are purely focused
      on either GPUs or CPUs. This work presents a hybrid approach that collaboratively
      combines the GPUs and CPUs available in a computer and applies it to the problem
      of tomographic reconstruction. Proper orchestration of workload in such a
      heterogeneous system is an issue. Here we use an on-demand strategy whereby the
      computing devices request a new piece of work to do when idle. Our hybrid
      approach thus takes advantage of the whole computing power available in modern
      computers and further reduces the processing time. This CPU+GPU co-processing can
      be readily extended to other image processing tasks in 3DEM.

PMID- 22475369
TI  - Nuclear noncoding RNA surveillance: is the end in sight?
AB  - Nuclear noncoding RNA (ncRNA) surveillance pathways play key roles in shaping the
      steady-state transcriptomes of eukaryotic cells. Defective and unneeded ncRNAs
      are primarily degraded by exoribonucleases that rely on protein cofactors to
      identify these RNAs. Recent studies have begun to elucidate both the mechanisms
      by which these cofactors recognize aberrant RNAs and the features that mark RNAs
      for degradation. One crucial RNA determinant is the presence of an accessible
      end; in addition, the failure of aberrant RNAs to fold into compact structures
      and assemble with specific binding proteins probably also contributes to their
      recognition and subsequent degradation. To date, ncRNA surveillance has been most
      extensively studied in budding yeast. However, mammalian cells possess nucleases
      and cofactors that have no known yeast counterparts, indicating that RNA
      surveillance pathways may be more complex in metazoans. Importantly, there is
      evidence that the failure of ncRNA surveillance pathways contributes to human
      disease.

PMID- 22475373
TI  - Progestins and antiprogestins affect gene expression in early development in
      zebrafish (Danio rerio) at environmental concentrations.
AB  - Progesterone (P4) and synthetic progestins (gestagens) from contraceptives and
      hormone therapy occur in treated wastewater and surface water, and they may have
      adverse effects on aquatic organisms. Little is known about the molecular and
      reproductive effects of P4 and synthetic progestins in fish, and effects of the
      antiprogestin mifepristone (RU486, an abortive) are unknown. We aimed at
      elucidating effects on the hormone system by quantitative determination of
      transcriptional changes of target genes induced by 2, 20, and 200 ng/L P4, RU486,
      norethindrone (NET), and levonorgestrel (LNG). We exposed zebrafish embryos for
      144 h post fertilization (hpf) to these compounds and analyzed expressional
      changes of ar, esr1, vtg1, hsd17beta3, and progesterone (pgr), mineralo- (mr),
      and glucocorticoid (gr) receptors, each at 48, 96, and 144 hpf. Concentrations of
      NET and LNG were constant during exposure, while P4 and RU486 decreased. P4 and
      RU486 were the most potent steroids. Significant up to 4-fold induction of pgr,
      ar, mr, and hsd17b3 occurred at 2 ng/L P4 and higher, while RU484 inhibited pgr
      expression. NET and LNG modulated some transcripts mainly above 2 ng/L. The
      expressional chances occurring at environmental levels may translate to negative
      interference with differentiation of brain and gonads, and consequently
      reproduction.

PMID- 22475374
TI  - An outbreak of post-partum breast abscesses in Mumbai, India caused by ST22-MRSA
      IV: genetic characteristics and epidemiological implications.
AB  - A cluster of methicillin-resistant Staphylococcus aureus (MRSA) breast abscesses
      in women who had given birth at a hospital in Mumbai, India was investigated
      retrospectively. Nineteen of 20 cases were caused by a single clone: pvl
      positive, spa type 648 (Ridom t852), ccrB:dru subtype 3:0, ST22-MRSA-IV. Despite
      the presence of pvl and SCCmec type IV, which are common genetic markers in
      community-associated MRSA, this outbreak was caused by a healthcare-associated,
      community-onset MRSA that was common in the hospital environment. Thus, infection
      control practices may have an important role in limiting the spread of this
      virulent clone.

PMID- 22475375
TI  - Completely beta-selective glycosylation using 3,6-O-(o-xylylene)-bridged axial
      rich glucosyl fluoride.
AB  - A completely beta-selective glycosylation that does not rely on neighboring group
      participation is described. The novelty of this work is the design of the
      glycosyl donor locked into the axial-rich form by the o-xylylene bridge between
      the 3-O and 6-O of d-glucopyranose. The synthesized 2,4-di-O-benzyl-3,6-O-(o
      xylyene)glucopyranosyl fluoride could efficiently react with various alcohols in
      a SnCl(2)-AgB(C(6)F(5))(4) catalytic system. The mechanism composed of the
      glycosylation and isomerization cycles was revealed through comparative
      experiments using acidic and basic molecular sieves. The achieved perfect
      stereocontrol is attributed to the synergy of the axial-rich conformation and
      convergent isomerization caused by HB(C(6)F(5))(4) generated in situ.

PMID- 22475376
TI  - Neuroprotective effects of adipose-derived stem cells against ischemic neuronal
      damage in the rabbit spinal cord.
AB  - Transplantation of adipose-derived stem cells (ASCs) is one of the possible
      therapeutic tools for ischemic damage. In this study, we observed the effects of
      ASCs against ischemic damage in the ventral horn of L(5-6) levels in the rabbit
      spinal cord. ASCs were isolated from rabbits, and cell type was confirmed by flow
      cytometry analysis, labeling with CM-DiI dye and differentiation into adipocytes
      in adipogenesis differentiation medium. ASCs were administered intrathecally into
      recipient rabbits (2 * 105) immediately after reperfusion following a 15-min
      aortic artery occlusion in the subrenal region. Transplantation of ASCs
      significantly improved functions of the hindlimb and morphology of the ventral
      horn of spinal cord although CM-DiI-labeled ASCs were not observed in the spinal
      cord parenchyma. In addition, transplantation of ASCs significantly increased
      brain-derived neurotrophic factor (BDNF) levels at 72h after
      ischemia/reperfusion. These results suggest that transplantation of ASCs prevents
      motor neurons from spinal ischemic damage and reactive gliosis by increasing
      neurotrophic factors such as BDNF in the spinal cord.

PMID- 22475377
TI  - Aeschynomene evenia, a model plant for studying the molecular genetics of the nod
      independent rhizobium-legume symbiosis.
AB  - Research on the nitrogen-fixing symbiosis has been focused, thus far, on two
      model legumes, Medicago truncatula and Lotus japonicus, which use a sophisticated
      infection process involving infection thread formation. However, in 25% of the
      legumes, the bacterial entry occurs more simply in an intercellular fashion.
      Among them, some Aeschynomene spp. are nodulated by photosynthetic Bradyrhizobium
      spp. that do not produce Nod factors. This interaction is believed to represent a
      living testimony of the ancestral state of the rhizobium-legume symbiosis. To
      decipher the mechanisms of this Nod-independent process, we propose Aeschynomene
      evenia as a model legume because it presents all the characteristics required for
      genetic and molecular analysis. It is a short-perennial and autogamous species,
      with a diploid and relatively small genome (2n=20; 460 Mb/1C). A. evenia
      'IRFL6945' is nodulated by the well-characterized photosynthetic Bradyrhizobium
      sp. strain ORS278 and is efficiently transformed by Agrobacterium rhizogenes.
      Aeschynomene evenia is genetically homozygous but polymorphic accessions were
      found. A manual hybridization procedure has been set up, allowing directed
      crosses. Therefore, it should be relatively straightforward to unravel the
      molecular determinants of the Nod-independent process in A. evenia. This should
      shed new light on the evolution of rhizobium-legume symbiosis and could have
      important agronomic implications.

PMID- 22475378
TI  - Inhibition of autophagy enhances the effects of E1A-defective oncolytic
      adenovirus dl922-947 against glioma cells in vitro and in vivo.
AB  - Oncolytic viruses represent a novel therapeutic approach for aggressive tumors,
      such as glioblastoma multiforme, which are resistant to available treatments.
      Autophagy has been observed in cells infected with oncolytic viruses; however,
      its role in cell death/survival is unclear. To elucidate the potential
      therapeutic use of autophagy modulators in association with viral therapy, we
      analyzed autophagy induction in human glioma cell lines U373MG and U87MG infected
      with the oncolytic adenovirus dl922-947. dl922-947 infection triggered an
      autophagic cellular response, as shown by the development of acidic vesicular
      organelles, LC3-I->LC3-II conversion, and reduction of p62 levels. However, on
      infection, the Akt/mTOR/p70s6k pathway, which negatively regulates autophagy, was
      activated, whereas the ERK1/2 pathway, a positive regulator of autophagy, was
      inhibited. Accordingly, MEK inhibition by PD98059 sensitized glioma cells to
      dl922-947 effects, whereas autophagy induction by rapamycin protected cells from
      dl922-947-induced death. Treatment with two inhibitors of autophagy, chloroquine
      and 3-methyladenine, increased the cytotoxic effects of dl922-947 in vitro. In
      vivo, the growth of U87MG-induced xenografts was further reduced by adding
      chloroquine to the dl922-947 treatment. In conclusion, autophagy acts as a
      survival response in glioma cells infected with dl922-947, thus suggesting
      autophagy inhibitors as adjuvant/neoadjuvant drugs in oncolytic virus-based
      treatments.

PMID- 22475379
TI  - Antiamnesic activity of Syzygium cumini against scopolamine induced spatial
      memory impairments in rats.
AB  - We evaluated the Antiamnesic effects of methanolic extract of Syzygium cumini
      (MESC) on spatial memory impairments induced by scopolamine (1 mg/kg, i.p.), a
      muscarinic antagonist, using the Radial arm maze, Morris water maze, learned
      helpless ness tests. Effect of MESC was evaluated and compared to standard drug,
      piracetam (200 mg/kg, i.p.). The MESC significantly (p<0.05) improved the
      impairment of short term or working memory induced by scopolamine in the Radial
      arm maze test, and significantly (p<0.05) reversed cognitive impairments in rats
      as measured by the learned helplessness test. In addition, MESC decreased escape
      latencies in the Morris water maze test. The activity of acetylcholinesterase in
      the brain was inhibited significantly (p<0.05) by treatment with MESC to a level
      similar to that observed in rats treated with piracetam. Moreover treatment with
      MESC (200 and 400 mg/kg, p.o.) to scopolamine induced rats significantly (p<0.05)
      decreased TBARS levels which was accompanied by an increase in the activities of
      SOD and Catalase. MESC has dose dependent effect and 400 mg/kg dose shown more
      prominent results when compared to 200 mg/kg dose of MESC. These results indicate
      that MESC may exert anti-amnesic activity via inhibition of acetylcholinesterase
      and antioxidant mechanisms in the brain.

PMID- 22475380
TI  - The Experience of Caregiving Inventory for first-episode psychosis caregivers:
      validation of the Brazilian version.
AB  - Family members of first-episode psychosis (FEP) patients are regarded as key
      components of the patient's evaluation, recovery and treatment. This paper aimed
      to investigate 75 FEP caregivers' appraisal, psychological morbidity and quality
      of life in the initial phase of treatment in a specialized FEP outpatient program
      in Sao Paulo, Brazil, and evaluate the validation of the Brazilian version of the
      Experience of Caregiving Inventory (ECI). Caregivers were also scored through
      Self Report Questionnaire-20 and Short Form-36. It was found that 29% of them
      might be a case for minor psychiatric disorder, that the worst domains of quality
      of life concerned emotional aspects, vitality and bodily pain, and that they were
      particularly affected by patients' negative symptoms, dependency and difficult
      behaviors. Additionally, internal consistency of ECI was very satisfactory
      (Cronbach's alpha=0.95) with subscales ranging from 0.57 (stigma) to 0.94 (total
      negative score). The Brazilian version of the ECI is not only a facile, reliable
      and valid instrument to describe the experience of caring for a relative with
      serious mental illness. It offers mental health professionals an opportunity to
      access caregivers' global experience and their evaluation of a severe mental
      disease, as well as to predict their psychological suffering, which is harmful to
      both patient and caregiver.

PMID- 22475382
TI  - Increased gray matter density in patients with schizophrenia and cannabis use: a
      voxel-based morphometric study using DARTEL.
AB  - Alterations in gray matter density as well as cognitive impairments are commonly
      described in patients with schizophrenia (SCH patients). Both gray matter
      deficits and cognitive impairments have recently been discussed to represent
      vulnerability markers of schizophrenia. The counterintuitive finding of better
      cognitive performance in patients with schizophrenia and cannabis use (SCH+CAN
      patients) compared to cannabis naive patients is discussed as a reflection of
      lower vulnerability for schizophrenia in at least one subgroup of SCH+CAN
      patients. We hypothesized that SCH+CAN patients would display fewer gray matter
      deficits compared to SCH patients reflecting their presumed lower vulnerability.
      We therefore compared gray matter density in 30 first episode SCH+CAN and 24
      first episode SCH patients using a fast diffeomorphic registration algorithm
      (DARTEL) and voxel-based morphometry (VBM). We found less severe cognitive
      impairments and middle frontal gray matter deficits in the SCH+CAN patients. In
      the pooled sample gray matter density was positively associated with cognitive
      functioning. Results may support the hypothesis of a lower biological
      vulnerability in at least one subgroup of SCH+CAN patients.

PMID- 22475381
TI  - Multimodal analyses identify linked functional and white matter abnormalities
      within the working memory network in schizophrenia.
AB  - BACKGROUND: Dysconnectivity between brain regions is thought to underlie the
      cognitive abnormalities that characterise schizophrenia (SZ). Consistent with
      this notion functional magnetic resonance imaging (fMRI) and diffusion tensor
      imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in
      functional integration and in white matter connectivity. Yet little is known
      about how alterations at the functional level related to abnormalities in
      anatomical connectivity. METHODS: We obtained fMRI data during the 2-back working
      memory task from 25 patients with SZ and 19 healthy controls matched for age, sex
      and IQ. DTI data were also acquired in the same session. In addition to
      conventional unimodal analyses we extracted "features" [contrast maps for fMRI
      and fractional anisotropy (FA) for DTI] that were subjected to joint independent
      component analysis (JICA) in order to examine interactions between fMRI and DTI
      data sources. RESULTS: Conventional unimodal analyses revealed both functional
      and structural deficits in patients with SZ. The JICA identified regions of
      joint, multimodal brain sources that differed in patients and controls. The fMRI
      source implicated regions within the anterior cingulate and ventrolateral
      prefrontal cortex and in the cuneus where patients showed relative hypoactivation
      and within the frontopolar cortex where patients showed relative hyperactivation.
      The DTI source localised reduced FA in patients in the splenium and posterior
      cingulum. CONCLUSIONS: This study promotes our understanding of structure
      function relationships in SZ by characterising linked functional and white matter
      changes that contribute to working memory dysfunction in this disorder.

PMID- 22475383
TI  - No evidence for familial covariation of neurocognition and negative symptoms in
      psychotic disorders.

PMID- 22475384
TI  - Association between fetal gender and the first stage labor curve: clinical
      consideration.

PMID- 22475385
TI  - Factors influencing urinary fistula repair outcomes in developing countries: a
      systematic review.
AB  - We reviewed literature examining predictors of urinary fistula repair outcomes in
      developing country settings, including fistula and patient characteristics, and
      perioperative factors. We searched Medline for articles published between January
      1970 and December 2010, excluding articles that were (1) case reports, cases
      series or contained 20 or fewer subjects; (2) focused on fistula in developed
      countries; and (3) did not include a statistical analysis of the association
      between facility or individual-level factors and surgical outcomes. Twenty
      articles were included; 17 were observational studies. Surgical outcomes included
      fistula closure, residual incontinence after closure, and any incontinence (dry
      vs wet). Scarring and urethral involvement were associated with poor prognosis
      across all outcomes. Results from randomized controlled trials examining
      prophylactic antibiotic use and repair outcomes were inconclusive. Few
      observational studies examining perioperative interventions accounted for
      confounding by fistula severity. We conclude that a unified, standardized
      evidence-base for informing clinical practice is lacking.

PMID- 22475386
TI  - Random mutagenesis suggests that sequence errors are not a major cause of
      variation in the activity of individual molecules of beta-galactosidase.
AB  - Wild-type Escherichia coli lacZ was subjected to error-prone PCR to generate two
      plasmid-encoded gene libraries containing approximately 2.6 (SD 1.9) nucleotide
      exchanges resulting in 1.8 (SD 1.4) amino-acid substitutions. The libraries were
      used, along with a plasmid containing wild-type lacZ, to transform E. coli
      lacking genomic lacZ. Cells expressing functional beta-galactosidase were
      identified by blue/white screening. Cell lysates containing the populations of
      heterogeneously mutagenized beta-galactosidase were subjected to single molecule
      assays using a capillary electrophoresis laser-induced fluorescence-based
      protocol. There was no significant difference in the average catalytic rate
      between the random mutagenized and wild-type enzyme populations. Furthermore,
      there was no clear pattern between error rates and the variances in the
      population catalytic rates. This suggests that random sequence errors are not a
      substantial source of the catalytic heterogeneity of this enzyme.

PMID- 22475388
TI  - Low back pain during pregnancy caused by a sacral stress fracture: a case report.
AB  - INTRODUCTION: Sacral stress fractures are a rare but well known cause of low back
      pain. This type of fracture has also been observed as a postpartum complication.
      To date, no cases of intrapartum sacral stress fractures have been described in
      the literature. CASE PRESENTATION: We report the case of a 26-year-old Caucasian
      European primigravid patient (30 weeks and two days of gestation) who presented
      to our outpatient clinic with severe low back pain that had started after a
      downhill walk 14 days previously. She had no history of trauma. A magnetic
      resonance imaging scan revealed a non-displaced stress fracture of the right
      lateral mass of her sacrum. Following her decision to opt for non-operative
      treatment, our patient received an epidural catheter for pain control. The
      remaining course of her pregnancy was uneventful and our patient gave birth to a
      healthy child by normal vaginal delivery. CONCLUSIONS: We conclude that a sacral
      stress fracture must be considered as a possible cause of low back pain during
      pregnancy.

PMID- 22475389
TI  - Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans.
AB  - Toxicity of nano-formulated silver to eukaryotes was assessed by exposing
      nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs):
      with average primary particle diameters of 1 nm (AgNP1) and 28nm (AgNP28, PVP
      coated), respectively. Tests were performed with and without presence of
      Escherichia coli to evaluate how the presence of a food bacterium affects the
      AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre
      exposed to 0 and 1mgAgNPL(-1), respectively, for 20 h prior to exposure at higher
      concentrations of AgNP. Both AgNP1 and AgNP28 showed adverse dose-response
      effects and mortality on C. elegans. LC(50) for AgNP28 was lower than for AgNP1
      and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic
      than AgNP1. Including E. coli in the test medium as a food source increased AgNPs
      toxicity towards nematodes compared to when bacteria were not present. Pre
      exposure to a low-level AgNP1 concentration made the nematodes slightly more
      sensitive to further exposure at higher concentrations compared to no pre
      exposure, indicating that nematodes have no efficient physiological ability to
      counteract nano-silver toxicity by acclimation. The amount of dissolved Ag(+) was
      0.18 to 0.21 mg L(-1) after 20 h at the highest AgNP1 (10 mg L(-1)) and AgNP28 (3
      mg L(-1)) doses in the exposure medium, respectively. The upper limit of Ag(+)
      solubility cannot immediately explain the dose-response-related toxic effects of
      the AgNP nor the difference between AgNP1 and AgNP28. Higher toxicity of AgNP28
      than AgNP1 may be explained by a combination of effects of coating, Ag-solubility
      and higher uptake rates due to agglomeration into MUm-size agglomerates in the
      exposure medium.

PMID- 22475390
TI  - Defining reference values of trace elements in the tear film: diagnostic methods
      and possible applications.
AB  - The study has been performed on tears of apparently healthy subjects who live and
      work in urban and rural areas, respectively. After the collection the following
      elements were investigated: chromium (Cr); arsenic (As); copper (Cu); zinc (Zn);
      selenium (Se); rubidium (Rb); barium (Ba); lead (Pb) and cobalt (Co).
      Significantly higher values of As were found in subjects living and working in
      rural areas as compared to those found in urban area residents (0.290 vs. 0.025;
      p<0.001). Conversely, Ba and Pb were significantly lower in rural area residents
      (1.10 vs. 2.50, p=0.027 and 1.70 vs. 1.10, p=0.057, respectively). Our data show
      that trace elements analysis in tears is possible; further studies could define
      if it could be a reliable biomarker in persons exposed to high concentration of
      trace elements due to working or environmental reasons.

PMID- 22475391
TI  - Pharmacoeconomic considerations of treating patients with advanced Parkinson's
      disease.
AB  - INTRODUCTION: Parkinson's disease (PD) is one of the most common
      neurodegenerative diseases. In the later (advanced) stages of PD, the initial
      treatment of early PD becomes less effective and long-term side effects of
      dopaminergic treatment become apparent. In advanced PD, motor and non-motor
      complications occur, which increase treatment costs. Increasing disability and
      impaired activities of daily living concomitantly raise indirect costs, due to
      loss in productivity. Hence, the economic burden of advanced PD is substantial
      for both the society and the patients with their caregivers. AREAS COVERED: A
      systematic literature search was performed involving the databases NHS CRD
      (National Health Service Centre for Reviews and Dissemination) and PubMed until
      July 15, 2011. "Parkinson" [Mesh] and "cost" were used as search terms in PubMed
      and only "Parkinson" in the CRD database. EXPERT OPINION: Economic evaluations
      are scarce and heterogeneous, and their interpretation may be limited due to
      methodological shortcomings. Dopamine agonists, COMT and MAO-B inhibitors as well
      levodopa infusion and deep brain stimulation are reported to be cost-effective in
      the respective decision frameworks. However, these results are heavily dependent
      on assumptions of drug costs and effect sizes used in the models. More detailed
      real-life information from long-term clinical trials is needed to feed the
      economic models, especially for head-to-head comparisons. To date, no economic
      evaluation has been undertaken for possible neuroprotective/disease modifying
      effects, and further research is needed for evaluations of interventions for non
      motor symptoms.

PMID- 22475392
TI  - Evidence of redox unbalance in post-acute ischemic stroke patients.
AB  - Measurements of the redox balance after the ischemic stroke occurrence might be
      useful to monitor the outcome of patients who suffered an ischemic stroke in
      terms of stroke recurrence and other vascular events. For this purpose, fifteen
      patients (mean age 71.40+/-2.50 years) with a first-ever ischemic stroke were
      included in the study within 30 days of stroke onset. Stroke severity was
      evaluated according to the National Institutes of Health Stroke Scale (NIHSS).
      Redox balance was assessed by measuring plasma amount of total peroxidative by
      products, nitrite/nitrate metabolites (NOx), as expression of nitric oxide (NO)
      plasma bioavailability, total plasma antioxidant capacity (TEAC), Cu/Zn
      Superoxide Dismutase (Cu/Zn SOD) activity, serum urate concentration and
      autoantibodies against ox-LDL (OLAB) serum level. Total cholesterol,
      triglycerides, high density lipoprotein-cholesterol (HDL-C) and low density
      lipoprotein-cholesterol (LDL-C) were also measured. Fifteen apparently healthy
      controls (mean age 70.28+/-2.03 years) were investigated to compare redox
      markers. Stroke patients had higher plasma values of total peroxidative by
      products, NOx stable metabolites and of total cholesterol, triglycerides, and LDL
      C than controls (P < 0.05). No differences in OLAB levels, Cu/Zn-SOD activity,
      serum urate concentration, and plasma HDL-C amount were found in stroke patients
      when compared to controls. Total plasma antioxidant capacity was lower in stroke
      patients than in controls. NOx values correlated positively with the NIHSS score
      in stroke patients (r=0.668; P=0.0065). The observed presence of redox unbalance
      in stroke patients could represent an early indicator of diffuse endothelial
      activation during which patients may be at increased risk of stroke recurrence
      and other vascular events.

PMID- 22475394
TI  - Crocetin, a carotenoid derivative, inhibits VEGF-induced angiogenesis via
      suppression of p38 phosphorylation.
AB  - We evaluated the protective effects of crocetin against angiogenesis induced by
      vascular endothelial growth factor (VEGF). Crocetin, the aglycone of crocin
      carotenoids, is found in saffron crocus (Crocus sativus L.) and gardenia fruit
      (Gardenia jasminoides Ellis). The effects of crocetin on VEGF-induced
      angiogenesis were examined by in vitro tube formation assays and following 14-day
      co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts.
      The anti-angiogenic mechanism of crocetin was evaluated by examining its effects
      on VEGF-induced proliferation and migration of human retinal microvascular
      endothelial cells (HRMECs) and phosphorylation of p38. Vascular endothelial (VE)
      cadherin, zonula occludens (ZO-1) and occludin, which are adherens and tight
      junction proteins, respectively, play a major role in the control of vascular
      permeability. Therefore, we tested effects of crocetin on adhesion molecule
      dissociation induced by VEGF. Crocetin significantly suppressed VEGF-induced tube
      formation by HUVECs and migration of HRMECs. It also significantly inhibited
      phosphorylation of p38 and protected VE-cadherin expression. These findings
      indicate that crocetin suppresses the VEGF-induced angiogenesis by inhibiting
      migration and that the inhibition of phosphorylated-p38 and protection of VE
      cadherin expression may be involved in its underlying mechanism of action.

PMID- 22475395
TI  - Temporal progression of kainic acid induced changes in vascular laminin
      expression in rat brain with neuronal and glial correlates.
AB  - We recently demonstrated a dramatic up regulation of laminin expression within
      the blood vessels of brain regions vulnerable to excitotoxin mediated neuronal
      degeneration. Although this effect was clearly demonstrable at 2 days post kainic
      acid exposure, its expression at shorter and longer post-dosing intervals has not
      been reported. Therefore, a primary goal of the present study was to characterize
      the laminin labeling at intervals ranging from 4 hours to 2 months following i.p.
      injection of kainic acid. To better characterize the nature and possible
      underlying mechanism of action of the changes in laminin expression, both Fluoro
      Jade C and GFAP immunohistochemistry were employed respectively at all survival
      intervals. At the shortest intervals examined (4hr, 8hr), Fluoro-Jade C positive
      cells could be detected in the hippocampus, thalamus, and piriform cortex. In
      these same regions, both vascular laminin and astrocytic GFAP expression were up
      regulated. At intermediate survival intervals (2, 5, 14, and 21 days), the
      respective labeling of degenerating neurons, astrocytes and capillaries were all
      maximal. Morphologically, Fluoro-Jade C labeled degenerating neurons were labeled
      in their entirety, GFAP positive astrocytes appeared hypertrophic and blood
      vessels took on a fragmented appearance. Hypertrophied GFAP positive astrocytes
      were conspicuous around periphery of the lesion but absent within the core of the
      lesion at these times. At longer survival intervals (1-2 months), the number of
      FJ-C labeled degenerating neurons was greatly reduced, while GFAP staining
      essentially returned to base line and laminin expression remained noticeably
      elevated, although the vessels appeared to be intact morphologically. These data
      allow for speculation on possible mechanisms underlying these events.

PMID- 22475393
TI  - WISP1 (CCN4) autoregulates its expression and nuclear trafficking of beta-catenin
      during oxidant stress with limited effects upon neuronal autophagy.
AB  - Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4) is a CCN family member
      more broadly identified with development and tumorigenesis. However, recent
      studies have shed new light and enthusiasm on WISP1 as a novel target directed
      against toxic cell degeneration. Here we show WISP1 prevents apoptotic
      degeneration in primary neurons during oxidant stress through the activation of
      protein kinase B (Akt1), the post-translational maintenance of beta-catenin
      integrity that is consistent with inhibition of glycogen synthase kinase-3beta
      (GSK-3beta), and the subcellular trafficking of beta- catenin to foster its
      translocation to the nucleus. Interestingly, WISP1 autoregulates its expression
      through the promotion of beta-catenin activity and may employ beta-catenin to
      have a limited control over autophagy, but neuronal injury during oxidant stress
      as a result of autophagy appears portioned to a small population of neurons
      without significant impact upon overall cell survival. New strategies that target
      WISP1, its autoregulation, and the pathways responsible for neuronal cell injury
      may bring forth new insight for the treatment of neurodegenerative disorders.

PMID- 22475396
TI  - Multigate quality Doppler profiles and morphological/hemodynamic alterations in
      multiple sclerosis patients.
AB  - Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous
      insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims
      were to assess interobserver variability in ultrasound evaluation of MS patients
      and to relate echo-markers to MS clinical symptoms and the disability degree. 277
      MS patients (117 men, mean age 43.05+10.04 years) admitted to the Neurology
      Department of Bari University General Hospital, underwent clinical, Expanded
      Disability Status Scale (EDSS) evaluation, and a cerebro-venous system ECD
      evaluation. Two operators reevaluated 32 patients to calculate interobserver
      variability. McNemar test confirmed the procedure reproducibility between two
      operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux
      [right: 16% absence vs. 58% presence, p < 0.0001; left: 26% vs. 50%, p < 0.0001];
      their absence in Primary Progressive (PP) MS form [right: 11% vs. 2%, p < 0.001;
      left: 12% vs. 2%, p < 0.001]. Internal jugular veins (IJVs) reflux absence was in
      Relapsing-remitting (RR) form [right: 60% vs. 74%, p=0.036; left: 56% vs. 85%, p
      < 0.0001] like hemodynamically significant stenosis [right: 57% vs. 69%, p=0.033;
      left: 49% vs. 73%, p < 0.001] not present in PP [right: 11% vs. 2%, p < 0.001;
      left: 10% vs. 3%, p=0.009]. A supine IJVs blocked flow was related to the EDSS
      class [right: 4.8+/-1.5 vs. 5.4+/-1.4, p=0.006; left: 4.7+/-1.6 vs. 5.5+/-1.2, p
      < 0.0001]; its absence was linked to RR [right: 60% vs. 76%, p=0.016; left: 58%
      vs. 79%, p < 0.001]. ECD has an important value in MS patients with IJV anomalies
      detection and a good interobserver procedure reproducibility. MS is associated
      with CCSVI, although further studies are needed.

PMID- 22475397
TI  - Serum bilirubin after acute ischemic stroke is associated with stroke severity.
AB  - Elevated serum bilirubin was prevalent in the acute ischemic stroke (AIS), which
      was induced in response to oxidative stress and could display the intensity of
      oxidative stress. As more severe stroke is linked with higher level of oxidative
      stress, we hypothesized that bilirubin may be associated with the severity of
      stroke. In this study, bilirubin and other biochemical indexes were measured in
      531 enrolled patients with AIS, and NIH Stroke Scale (NIHSS) scores were assessed
      simultaneous with blood collection. The association between bilirubin and the
      severity of stroke was performed by Spearman correlation analyze, and the level
      risk relationship of bilirubin in different level of NIHSS score was performed
      through Multinomial logistic regression analysis. We performed multivariable
      logistic regression to estimate odds ratios (OR) and 95% confidence intervals
      (CI) of severe stroke dichotomized as NIHSS>=8 with adjustment for other stroke
      risk factors, the level-risk relationship of severe stroke in different level of
      bilirubin was also performed through Multinomial logistic regression analysis. We
      found that NIHSS score was significantly positively correlated with both serum
      direct bilirubin (Dbil, R=0.229 and P=0.000) and total bilirubin (Tbil, R=0.224
      and P=0.000), higher level of serum bilirubin linked to the higher NIHSS score
      with OR(95% CI) in upper level of NIHSS score group was 1.12(1.01-1.24),
      1.23(1.11-1.36), 1.31(1.15-1.51) in Dbil and 1.01(0.99-1.31), 1.05(1.03-1.08),
      1.07(1.03-1.11) in Tbil compared to the lowest level group. In unadjusted or
      adjusted logistic regression analyses, serum Dbil and Tbil still have a
      significant association with the severe stroke. When both the Dbil and Tbil
      concentrations were grouped into 4 levels, participants with higher levels of
      bilirubin showed higher risk with severe stroke compared with the lowest level of
      bilirubin, with OR(95% CI) 1.881(1.04-3.404) of Dbil in level 3 and 3.702(1.979
      6.927) of Tbil, 3.352(1.572-7.147) of total bilirubin in level 4. As a
      conclusion, serum bilirubins were in significant correlation with severity of
      AIS, which may be served as useful markers to reflect the degree of illness.

PMID- 22475398
TI  - Dual targeting of glioma U251 cells with nanoparticles prevents tumor
      angiogenesis and inhibits tumor growth.
AB  - Important advances have been made within in past few years in the treatment of
      glioma, however, the longterm prognosis after resection of glioma remains
      unsatisfactory as a result of a high incidence of recurrence. To solve this
      problem, many biologic therapies have been investigated. In the present study, we
      report a nanoparticle with properties for dual targeting of tumor cells and the
      neovasculature. The nanoparticle comprises encoding vasohibin and RGD 12-mer
      cationic peptide RKKRRQRRRRGD (Tat49-57RGD) peptides, which a nuclear
      nanoparticle within an extranuclear peptide envelope. Our results demonstrate
      that the nanoparticle could prevent tumor angiogenesis and inhibit tumor growth
      via attenuating neovasculature formation and inducing tumor apoptosis. Therefore,
      the dual targeting strategy of tumor cells and neovasculature represents an
      integrative approach in glioma therapy. This can be extended to additional agents
      to target multiple signal pathways or distinct tumor compartments.

PMID- 22475399
TI  - Cisternal sustained release dihydropyridines for subarachnoid hemorrhage.
AB  - Nimodipine improved outcome in patients with subarachnoid hemorrhage (SAH)
      although hypotension limited the dose that could be administered systemically.
      Subarachnoid delivery of nicardipine or nimodipine may be more efficacious. We
      tested the efficacy of cisternal application of sustained release nicardipine and
      nimodipine in SAH in monkeys and dogs, respectively. SAH was created in 13
      cynomolgus macaques by placement of autologous blood clot around right middle
      cerebral, anterior cerebral, and internal carotid arteries. Placebo poly-D,L
      lactide coglycolide (PLGA), nicardipine PLGA or mibefradil PLGA was inserted in
      the clots. Catheter and computed tomography angiography (CTA) were performed at
      baseline and 7 days later (day 7). Cerebral infarction was assessed on day 7 by
      magnetic resonance imaging. Six dogs underwent baseline angiography and injection
      of autologous blood plus PLGA or nimodipine-loaded PLGA microparticles into the
      cisterna magna. Blood injection was repeated 2 days later and angiography 7 and
      14 days later. Animals were euthanized and brains were examined histologically.
      Cerebrospinal fluid and serum nimodipine concentrations were measured.
      Nicardipine, but not mibefradil PLGA decreased vasospasm in monkeys (paired t
      tests) although there was no significant effect on infarctions see on MRI. In
      dogs, nimodipine-PLGA produced high local concentrations of nimodipine that were
      associated with reduced basilar artery vasospasm. No untoward histological
      effects were observed. There was no reduction in microthrombi in animals treated
      with nimodipine PLGA compared to placebo PLGA. Site-specific, sustained release
      formulations of dihydropyridines can deliver high concentrations to the
      cerebrospinal fluid without causing systemic side effects, and may reduce
      angiographic vasospasm after SAH. Since nimodipine improves outcome in patients
      with SAH without necessarily preventing vasospasm, further studies are warranted.

PMID- 22475400
TI  - Double inversion of emulsions induced by salt concentration.
AB  - The effects of salt on emulsions containing sorbitan oleate (Span 80) and
      Laponite particles were investigated. Surprisingly, a novel double phase
      inversion was induced by simply changing the salt concentration. At fixed
      concentration of Laponite particles in the aqueous phase and surfactant in
      paraffin oil, emulsions are oil in water (o/w) when the concentration of NaCl is
      lower than 5 mM. Emulsions of water in oil (w/o) are obtained when the NaCl
      concentration is between 5 and 20 mM. Then the emulsions invert to o/w when the
      salt concentration is higher than 50 mM. In this process, different emulsifiers
      dominate the composition of the interfacial layer, and the emulsion type is
      correspondingly controlled. When the salt concentration is low in the aqueous
      dispersion of Laponite, the particles are discrete and can move to the interface
      freely. Therefore, the emulsions are stabilized by particles and surfactant, and
      the type is o/w as particles are in domination. At intermediate salt
      concentrations, the aqueous dispersions of Laponite are gel-like, the viscosity
      is high, and the transition of the particles from the aqueous phase to the
      interface is inhibited. The emulsions are stabilized mainly by lipophilic
      surfactant, and w/o emulsions are obtained. For high salt concentration,
      flocculation occurs and the viscosity of the dispersion is reduced; thus, the
      adsorption of particles is promoted and the type of emulsions inverts to o/w.
      Laser-induced fluorescent confocal micrographs and cryo transmission electron
      microscopy clearly confirm the adsorption of Laponite particles on the surface of
      o/w emulsion droplets, whereas the accumulation of particles at the w/o emulsion
      droplet surfaces was not observed. This mechanism is also supported by the
      results of rheology and interfacial tension measurements.

PMID- 22475401
TI  - Decision aid tools to support women's decision making in pregnancy and birth: a
      systematic review and meta-analysis.
AB  - Support for a model of shared medical decision making, where women and their care
      providers discuss risks and benefits of their different options, reveal their
      preferences, and jointly make a decision, is a growing expectation in obstetric
      care. The objective of this study was to conduct a systematic review and meta
      analysis of randomized controlled trials evaluating the efficacy of different
      decision aid tools compared to regular care for women facing several options in
      the specific field of obstetric care. We included published studies about
      interventions designed to aid mothers' decision making and provide information
      about obstetrical treatment or screening options. Following a search of
      electronic databases for articles published in English and French from 1994 to
      2010, we found ten studies that met the inclusion criteria. In this systematic
      review and meta-analysis we found that all decision aid tools, except for
      Decision Trees, facilitated significant increases in knowledge. The Computer
      based Information Tool, the Decision Analysis Tools, Individual Counseling and
      Group Counseling intervention presented significant results in reducing anxiety
      levels. The Decision Analysis Tools and the Computer-based Information tool were
      associated with a reduction in levels of decisional conflict. The Decision
      Analysis Tool was the only tool that presented evidence of an impact on the final
      choice and final outcome. Decision aid tools can assist health professionals to
      provide information and counseling about choices during pregnancy and support
      women in shared decision making. The choice of a specific tool should depend on
      resources available to support their use as well as the specific decisions being
      faced by women, their health care setting and providers.

PMID- 22475402
TI  - Is harm reduction profitable? An analytical framework for corporate social
      responsibility based on an epidemic model of addictive consumption.
AB  - This article aims to help resolve the apparent paradox of producers of addictive
      goods who claim to be socially responsible while marketing a product clearly
      identified as harmful. It advances that reputation effects are crucial in this
      issue and that determining whether harm reduction practices are costly or
      profitable for the producers can help to assess the sincerity of their discourse.
      An analytical framework based on an epidemic model of addictive consumption that
      includes a deterrent effect of heavy use on initiation is developed. This
      framework enables us to establish a clear distinction between a simple
      responsible discourse and genuine harm reduction practices and, among harm
      reduction practices, between use reduction practices and micro harm reduction
      practices. Using simulations based on tobacco sales in France from 1950 to 2008,
      we explore the impact of three corresponding types of actions: communication on
      damage, restraining selling practices and development of safer products on total
      sales and on the social cost. We notably find that restraining selling practices
      toward light users, that is, preventing light users from escalating to heavy use,
      can be profitable for the producer, especially at early stages of the epidemic,
      but that such practices also contribute to increase the social cost. These
      results suggest that the existence of a deterrent effect of heavy use on the
      initiation of the consumption of an addictive good can shed new light on
      important issues, such as the motivations for corporate social responsibility and
      the definition of responsible actions in the particular case of harm reduction.

PMID- 22475403
TI  - The long-term impact of war on health and wellbeing in Northern Vietnam: some
      glimpses from a recent survey.
AB  - War is deemed a major threat to public health; yet, the long-term effects of war
      on individual health have rarely been examined in the context of developing
      countries. Based on data collected as a pilot follow-up to the Vietnam
      Longitudinal Survey, this study examines current health profiles of northern
      Vietnamese war survivors who entered early adulthood during the Vietnam War and
      now represent Vietnam's older adult population. To ascertain how war and military
      service in the early life course may have had long-term impacts on health status
      of Vietnam's current older adults, we compare multi-dimensional measures of
      health among veterans and nonveterans, and within these groups, regardless of
      their military service, between combatants and noncombatants. Multivariate
      results suggest that despite prolonged exposure to war, veterans and those who
      served in combat roles are not significantly different from their civilian and
      noncombatant counterparts on most health outcomes later in life. This is in
      contrast to American veterans who fought on the opposing side of the war. The
      near absence of differences in older adult health among northern Vietnamese with
      varying degrees of war involvement might be explained by the encompassing extent
      of war; the notion that time heals; and the hardiness and resilience against ill
      health that are by-products of shared struggle in war and a victorious outcome.

PMID- 22475405
TI  - Social network influences on adolescent substance use: disentangling structural
      equivalence from cohesion.
AB  - This study investigates two contagion mechanisms of peer influence based on
      direct communication (cohesion) versus comparison through peers who occupy
      similar network positions (structural equivalence) in the context of adolescents'
      drinking alcohol and smoking. To date, the two contagion mechanisms have been
      considered observationally inseparable, but this study attempts to disentangle
      structural equivalence from cohesion as a contagion mechanism by examining the
      extent to which the transmission of drinking and smoking behaviors attenuates as
      a function of social distance (i.e., from immediate friends to indirectly
      connected peers). Using the U.S. Add Health data consisting of a nationally
      representative sample of American adolescents (Grades 7-12), this study measured
      peer risk-taking up to four steps away from the adolescent (friends of friends of
      friends of friends) using a network exposure model. Peer influence was tested
      using a logistic regression model of alcohol drinking and cigarette smoking.
      Results indicate that influence based on structural equivalence tended to be
      stronger than influence based on cohesion in general, and that the magnitude of
      the effect decreased up to three steps away from the adolescent (friends of
      friends of friends). Further analysis indicated that structural equivalence acted
      as a mechanism of contagion for drinking and cohesion acted as one for smoking.
      These results indicate that the two transmission mechanisms with differing
      network proximities can differentially affect drinking and smoking behaviors in
      American adolescents.

PMID- 22475406
TI  - Stress associated with caregiving: an examination of the stress process model
      among Kenyan Luo elders.
AB  - Globally, a growing number of grandparents are caring for their grandchildren.
      The impact and burden associated with increases in custodial grandparenting,
      however, may differ by culture. In the United States, the caregiving role has
      been shown to be a significant source of stress for older adults. In cultures in
      which grandparents are more commonly involved in the care of young children,
      however, increasing caregiving roles may not be viewed as stressful. This study
      examines the impact of caregiving on perceived and physiological measures of
      stress among 640 Luo elders (60+) in western Kenya, where high HIV prevalence
      among younger-to-middle aged adults has led to a heavy burden of orphan care.
      Perceived stress levels were measured using the Luo Perceived Stress Scale
      (LPSS). Salivary cortisol and casual blood pressure were used as biomarkers of
      stress. Results were analyzed using random mixed effects models. Overall this
      study showed that caregivers have higher levels of perceived stress than non
      caregivers. For women, household composition, including the number of orphans and
      adults in the homestead impacted perceived stress. Among men, those who perceived
      caregiving as burdensome had higher perceived stress. Despite the association
      between caregiving and perceived stress, there was a minimal relationship between
      caregiving and the two biomarkers of stress. This may be because caregiving is
      superimposed onto other stressors and therefore has a minimal physiological
      impact. These results highlight the importance of local context in determining
      the impact of the caregiving role on older adult well-being.

PMID- 22475407
TI  - The persistence of health inequalities in modern welfare states: the explanation
      of a paradox.
AB  - The persistence of socioeconomic inequalities in health, even in the highly
      developed 'welfare states' of Western Europe, is one of the great disappointments
      of public health. Health inequalities have not only persisted while welfare
      states were being built up, but on some measures have even widened, and are not
      smaller in European countries with more generous welfare arrangements. This paper
      attempts to identify potential explanations for this paradox, by reviewing nine
      modern 'theories' of the explanation of health inequalities. The theories
      reviewed are: mathematical artifact, fundamental causes, life course perspective,
      social selection, personal characteristics, neo-materialism, psychosocial
      factors, diffusion of innovations, and cultural capital. Based on these theories
      it is hypothesized that three circumstances may help to explain the persistence
      of health inequalities despite attenuation of inequalities in material conditions
      by the welfare state: (1) inequalities in access to material and immaterial
      resources have not been eliminated by the welfare state, and are still
      substantial; (2) due to greater intergenerational mobility, the composition of
      lower socioeconomic groups has become more homogeneous with regard to personal
      characteristics associated with ill-health; and (3) due to a change in
      epidemiological regime, in which consumption behavior became the most important
      determinant of ill-health, the marginal benefits of the immaterial resources to
      which a higher social position gives access have increased. Further research is
      necessary to test these hypotheses. If they are correct, the persistence of
      health inequalities in modern European welfare states can partly be seen as a
      failure of these welfare states to implement more radical redistribution
      measures, and partly as a form of 'bad luck' related to concurrent developments
      that have changed the composition of socioeconomic groups and made health
      inequalities more sensitive to immaterial factors. It is argued that normative
      evaluations of health inequalities should take these explanations into account,
      and that a direct attack on the personal, psychosocial and cultural determinants
      of health inequalities may be necessary to achieve a substantial reduction of
      health inequalities.

PMID- 22475408
TI  - The "knucklehead" approach and what matters in terms of health for formerly
      incarcerated Latino men.
AB  - In terms of the examination of the relationship between masculinity and health,
      there has been limited exploration of how the ways in which formerly incarcerated
      Latino men (FILM) construct their masculinities may conflict with public health
      messages. Using information gained from three years of ethnographic research that
      was conducted with formerly incarcerated Puerto Rican males in three urban
      communities in New York City, the authors examine what matters to FILM in terms
      of their health and well-being and what conflicts exist between public health
      prevention messages and FILM masculinity. Our results indicate the following: (1)
      major threats to the health of FILM, such as HIV risk behavior, alcohol and drug
      use and high caloric intake, are perceived as irrelevant to most of the FILM in
      the study; (2) young FILM believe that they engage in risky behaviors because of
      their "knucklehead" mentality and diminish their risks by becoming "street
      smart;" and (3) social isolation, loneliness and general risk-taking behavior
      among FILM are salient issues that have yet to be effectively addressed. Of our
      sample of 32 FILM, we identified 7 individuals who have transitioned from having
      a "knucklehead" approach in their lives to possessing a greater sense of
      awareness of health and social matters. These seven individuals followed either
      or both of the following pathways: (1) pursuing a college education or (2)
      becoming community leaders.

PMID- 22475409
TI  - Infant flow biphasic nasal continuous positive airway pressure (BP- NCPAP) vs.
      infant flow NCPAP for the facilitation of extubation in infants' <= 1,250 grams:
      a randomized controlled trial.
AB  - BACKGROUND: The use of mechanical ventilation is associated with lung injury in
      preterm infants and therefore the goal is to avoid or minimize its use. To date
      there is very little consensus on what is considered the "best non-invasive
      ventilation mode" to be used post-extubation. The objective of this study was to
      compare the effectiveness of biphasic nasal continuous positive airway pressure
      (BP-NCPAP) vs. NCPAP in facilitating sustained extubation in infants <= 1,250
      grams. METHODS: We performed a randomized controlled trial of BP-NCPAP vs. NCPAP
      in infants <= 1,250 grams extubated for the first time following mechanical
      ventilation since birth. Infants were extubated using preset criteria or at the
      discretion of the attending neonatologist. The primary outcome was the incidence
      of sustained extubation for 7 days. Secondary outcomes included incidence of
      adverse events and short-term neonatal outcomes. RESULTS: Sixty-seven infants
      received BP-NCPAP and 69 NCPAP. Baseline characteristics were similar between
      groups. The trial was stopped early due to increased use of non-invasive
      ventilation from birth, falling short of our calculated sample size of 141
      infants per group. The incidence of sustained extubation was not statistically
      different between the BP-NCPAP vs. NCPAP group (67% vs. 58%, P = 0.27). The
      incidence of adverse events and short-term neonatal outcomes were similar between
      the two groups (P > 0.05) except for retinopathy of prematurity which was noted
      to be higher (P = 0.02) in the BP-NCPAP group. CONCLUSIONS: Biphasic NCPAP may be
      used to assist in weaning from mechanical ventilation. The effectiveness and
      safety of BP-NCPAP compared to NCPAP needs to be confirmed in a large multi
      center trial as our study conclusions are limited by inadequate sample size.
      CLINICAL TRIALS REGISTRATION #: NCT00308789 SOURCE OF SUPPORT: Grant # 06-06,
      Physicians Services Incorporated Foundation, Toronto, Canada. Summit technologies
      Inc. provided additional NCPAP systems and an unrestricted educational
      grant.Abstract presented at The Society for Pediatric Research Meeting,
      Baltimore, USA, May 2nd-5th, 2009 and Canadian Paediatric Society Meeting, June
      23rd-29th, Ottawa, 2009.

PMID- 22475410
TI  - Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL
      K1).
AB  - The collectins are a group of innate immune proteins structurally characterized
      by their content of a carbohydrate recognition domain and a collagen-like region.
      Collectin liver 1 (CL-L1) and collectin 11 (CL-11, alias collectin kidney 1, CL
      K1) are the more recently described members of this group. Their genomic
      organization and protein structure reveal many similarities. However, CL-11 is a
      serum protein, whereas CL-L1 appears to be restricted to the cytosol of cells
      such as hepatocytes. Specificity analyses of the CRDs reveal some differences in
      their preferences for saccharides: CL-11 binds most avidly to l-fucose and d
      mannose, whereas CL-L1 shows preference for d-mannose, d-fucose, N
      acetylglucosamine, and surprisingly also d-galactose. CL-11 binds to various
      microorganisms including Escherichia coli, Candida albicans and Influenza A
      virus. Polymorphisms in the CL-11 gene (COLEC11) leading to deficiencies have
      recently been identified as causative for 3MC syndrome. The 3MC syndrome is
      associated with a wide spectrum of developmental features including facial
      dysmorphism, cognitive impairment, hearing loss and vesicorenal anomalies.
      Similar polymorphic associations were reported for the mannan-binding lectin
      associated serine protease 3 (MASP-3), and falls into line with the observation
      that CL-11 is found in circulating complexes with MASP-1/3. These findings
      suggest dual or overlapping functions of CL-11 in innate immunity and in fetal
      development.

PMID- 22475411
TI  - Principal component analysis for dental shade color.
AB  - OBJECTIVES: Conventional 3-dimensional color spaces such as L*a*b* or L*C*h have
      a limitation in that colors of materials can only be separated on the same
      hyperplane. Therefore, it would be useful to find appropriate axes for dental
      color analysis by analyzing spectral data itself, rather than conventional 3
      dimensional color spaces. METHODS: Hyperspectral data are detailed color spectra
      with narrow spectral bands over a continuous spectral range. We acquired
      hyperspectral data of the shade guides without specular reflection, and
      standardized them as reflectance data. Then, reflectance data were weighed by
      luminous efficiency function, and used in principal component analysis (PCA).
      Principal components (PCs) and their contribution, and values of respective
      shades to respective PCs were calculated as PC scores. RESULTS: Cumulate
      contribution rate of 1st to 3rd PCs were approximately 100%, which meant shade
      colors were very similar to each other. Respective PCs showed specific figures,
      and values of shades showed sequences unique to each PC, which were independent
      of each other; values to the 1st PC showed gradual changes with change in shade
      numbering, values to the 2nd PC showed relatively high scores on opaque shades,
      values to the 4th PC showed lower scores on B and C group shades, and values to
      the 6th PC showed differences between manufacturers. SIGNIFICANCE: Using PCA, we
      could find axes independent of the conventional 3-dimensional color spaces. These
      axes reflected certain changes which are not detected on conventional color
      spaces. Our methods are taking into account color matching under any illumination
      by focusing on the spectra themselves, and we can discuss about components of the
      teeth from spectra of resulting principal components. By applying our method to
      conventional systems, it would help diagnose color differences of dental
      materials.

PMID- 22475412
TI  - Process evaluation of an environmental and educational nutrition intervention in
      residential drug-treatment facilities.
AB  - OBJECTIVE: To evaluate the implementation of a controlled, 6-week, environmental
      and educational intervention to improve dietary intake and body composition, and
      to study the association of implementation fidelity with diet and body
      composition outcomes. DESIGN: A process evaluation documented participation, dose
      of nutrition education delivered, participant satisfaction, fidelity and
      completeness of the food environment intervention implementation, and context
      through observations and interviews with staff and residents. Intervention sites
      were scored and categorized as high or low participation and implementation and
      compared on essential elements of the food environment and on diet and body
      composition outcomes. SETTING: Six urban residential drug-treatment facilities in
      Upstate New York. SUBJECTS: Fifty-five primarily black and white men in
      residential drug-treatment programmes. RESULTS: Participants were exposed to 94 %
      and 69 % of the educational and environmental elements, respectively. High
      implementation sites were significantly more likely to provide water and 100 %
      juice, offer fruit or vegetable salad, offer choices of fruits and vegetables,
      and limit fried foods. Mixed-model analysis of covariance revealed that
      participants in the high participation and implementation sites reported greater
      reductions in total energy, percentage of energy from sweets, daily servings of
      fats, oils and sweets, and BMI over the intervention period. Participants in low
      participation and implementation sites reported greater reductions in percentage
      of energy from fat. Differential implementation of environmental elements limited
      the intervention impact. CONCLUSIONS: These findings document the contribution of
      changes in eating environments to facilitate dietary behaviour change in
      community residential substance-abuse settings.

PMID- 22475413
TI  - Adaptation of a trap door technique for the recovery of ovarian cortical biopsies
      from Cebus apella (capuchin monkey).
AB  - There is a paucity of efficient cryopreservation protocols for primordial
      follicles enclosed in the ovarian tissue from non-human primates (NHP), in
      special New World primates. Our objective was to establish an optimal procedure
      for the recovery of ovarian biopsies from capuchin monkeys. To this end, we
      adapted a trap door biopsy method. Follicular density and quality of the biopsies
      were evaluated and ultrasound analysis was performed before and continuously
      after surgery to assess ovarian structure. Ovarian tissue biopsies recovered by
      the trap door technique allowed the successful harvesting of primordial follicles
      from capuchin monkeys, and no complication was recorded. The female cycle was not
      affected by surgery and no adherence was found thereafter. In conclusion, the
      adaptation of a trap door biopsy method is a safe procedure and allows recovery
      of healthy primordial follicles.

PMID- 22475414
TI  - Chemical characterization of dissolved organic compounds from coastal sea surface
      microlayers (Baltic Sea, Germany).
AB  - The physicochemical properties of the sea surface microlayer (SML), i.e. the
      boundary layer between the air and the sea, and its impact on air-sea exchange
      processes have been investigated for decades. However, a detailed description
      about these processes remains incomplete. In order to obtain a better chemical
      characterization of the SML, in a case study three pairs of SML and corresponding
      bulk water samples were taken in the southern Baltic Sea. The samples were
      analyzed for dissolved organic carbon and dissolved total nitrogen, as well as
      for several organic nitrogen containing compounds and carbohydrates, namely
      aliphatic amines, dissolved free amino acids, dissolved free monosaccharides,
      sugar alcohols, and monosaccharide anhydrates. Therefore, reasonable analytical
      procedures with respect to desalting and enrichment were established. All
      aliphatic amines and the majority of the investigated amino acids (11 out of 18)
      were found in the samples with average concentrations between 53 ng L(-1) and
      1574 ng L(-1). The concentrations of carbohydrates were slightly higher,
      averaging 2900 ng L(-1). Calculation of the enrichment factor (EF) between the
      sea surface microlayer and the bulk water showed that dissolved total nitrogen
      was more enriched (EF: 1.1 and 1.2) in the SML than dissolved organic carbon (EF:
      1.0 and 1.1). The nitrogen containing organic compounds were generally found to
      be enriched in the SML (EF: 1.9-9.2), whereas dissolved carbohydrates were not
      enriched or even depleted (EF: 0.7-1.2). Although the investigated compounds
      contributed on average only 0.3% to the dissolved organic carbon and 0.4% to the
      total dissolved nitrogen fraction, these results underline the importance of
      single compound analysis to determine SML structure, function, and its potential
      for a transfer of compounds into the atmosphere.

PMID- 22475415
TI  - Structures of KlenTaq DNA polymerase caught while incorporating C5-modified
      pyrimidine and C7-modified 7-deazapurine nucleoside triphosphates.
AB  - The capability of DNA polymerases to accept chemically modified nucleotides is of
      paramount importance for many biotechnological applications. Although these
      analogues are widely used, the structural basis for the acceptance of the
      unnatural nucleotide surrogates has been only sparsely explored. Here we present
      in total six crystal structures of modified 2'-deoxynucleoside-5'-O-triphosphates
      (dNTPs) carrying modifications at the C5 positions of pyrimidines or C7 positions
      of 7-deazapurines in complex with a DNA polymerase and a primer/template complex.
      The modified dNTPs are in positions poised for catalysis leading to
      incorporation. These structural data provide insight into the mechanism of
      incorporation and acceptance of modified dNTPs. Our results open the door for
      rational design of modified nucleotides, which should offer great opportunities
      for future applications.

PMID- 22475416
TI  - Seroprevalence and risk factors for Neospora caninum in sheep in the state Minas
      Gerais, southeastern Brazil.
AB  - The aim of this study was to determine the prevalence and risk factors associated
      with infection due to Neospora caninum in serum samples from 488 sheep
      originating from 63 farms in 63 municipalities distributed across eight of the
      twelve mesoregions of the state Minas Gerais, southeastern Brazil. For detection
      of N. caninum the sheep serum samples were subjected to the indirect fluorescence
      antibody test (IFAT >= 50). To identify the risk factors associated with
      infection due to N. caninum a questionnaire was filled out for each herd by
      interviewing, the individual responsible for the herd, demanding information on
      the general characteristics of the property. Sixty-four sheep sera (13.1%; 95%
      CI=10.3-16.4) presented IgG-specific anti-N. caninum antibodies with the
      following titers: 50 (49; 76.6%), 100 (7; 10.9%), 200 (4; 6.2%), 400 (3; 4.7%)
      and 800 (1; 1.6%). The prevalence of infected sheep per mesoregion ranged from 0
      to 28.1%. Out of the 63 farms sampled, 31 (49.2%; 95% CI=36.4-62.1) presented at
      least one seropositive sheep. No significant association was found between the
      presence of anti-N. caninum antibodies and the risk factors evaluated on the
      farms, except for the mesoregion variable (p=0.004; OR=0.429; CI95%=0.182-1.008).
      These results indicate that there is a need for additional research to define the
      epidemiological importance of this parasite as a cause of reproductive problems
      in sheep herds in Minas Gerais.

PMID- 22475417
TI  - Immunohistochemical and polymerase chain reaction studies in Neospora caninum
      experimentally infected broiler chicken embryonated eggs.
AB  - The diagnostic characteristics of immunohistochemistry (IHC) and polymerase chain
      reaction (PCR) methods were studied in the tissues of broiler chicken embryos
      experimentally infected by Neospora caninum. An infection with N. caninum NC-1
      isolate was conducted in 70 broiler chicken embryonated eggs randomly divided
      into seven equal groups. After 8 days of incubation, six groups were inoculated
      with 10, 10(2), 10(3), 10(4), 10(5), and 10(6) doses of tachyzoites/embryonated
      egg. The 7th group was considered as control. The mortality rate and pathological
      changes of the dead embryos and hatched chickens up to 60 days old were noticed.
      Consecutive sections to those used for histopathological examination including
      the liver, heart, brain, and chorioalantoic (CA) membrane were subjected to IHC.
      The intensity and distribution of the immunostaining was graded as highly to
      mildly positive. For PCR procedure, DNA was extracted from 50mg of the tissues
      and primer pair Np21/Np6 was used for amplification of the Nc-5 gene. The results
      of the immunosignaling ranged from variable degrees of mild to moderate staining
      as dark-brown to brown and coarsely to finely granular, mostly within the
      cytoplasm of infected cells such as the endothelial cells of blood vessels. The
      parasite aggregation was more predominant in the heart than other tissues.
      Immunoreactivity for N. caninum antigen was multifocally moderate positive in the
      heart, liver and CA of the 10(3) dose, and also heart, liver, brain and CA of the
      10(4) dose. IHC showed mildly positive in the liver and heart of the chicken
      embryos infected with 10 and 10(2) tachyzoites, as well. The results of the PCR
      confirmed the existence of the parasite in all of the examined tissues from the
      10(3) and 10(4) doses. In conclusion, the results indicate a good agreement
      between IHC and PCR in diagnosis of neospora antigen in the infected tissues.

PMID- 22475418
TI  - [Ciprofloxacin-induced thrombopenia].

PMID- 22475419
TI  - Poly(A) tail shortening correlates with mRNA repression in tropoelastin
      regulation.
AB  - BACKGROUND: It has been shown for various organisms that expression of
      tropoelastin (TE) is high during fetal and neonatal growth and that it is reduced
      in adulthood by an unknown mechanism. OBJECTIVE: To highlight the process of TE
      mRNA repression in vivo, total RNA from human skin biopsies was analyzed and TE
      mRNA expression was compared in fetal and adult donors. METHODS: TaqMan Real-Time
      PCR, Poly(A) tail length assay, immunoblot. RESULTS: In this study a more than 30
      fold reduction of mature TE mRNA was detected whereas the decline on pre-mRNA
      level was not pronounced. This finding supports the hypothesis that the
      repression of mature TE mRNA is for the most part due to posttranscriptional
      mechanisms. Since deadenylation-dependent mRNA destabilization is the major decay
      pathway for most mRNAs, poly(A) tail length of mature TE mRNA was analyzed in
      fetal and adult human skin, lung and uterus, showing a profound reduction of
      poly(A) tail length in the adult samples. While TE mRNA is repressed in adult
      tissues in vivo, TGF-beta(1) has been shown to induce expression of TE mRNA in
      vitro on the posttranscriptional level. To analyze the underlying mechanism, TE
      mRNA poly(A) tail length was analyzed in human dermal fibroblasts after treatment
      with TGF-beta(1)in vitro. Besides the expected increase in TE expression, TGF
      beta(1) treatment resulted in a significant stabilization of TE mRNA poly(A) tail
      length. CONCLUSION: Our findings correlate for the first time TE expression level
      with poly(A) tail length and suggest that maintenance of poly(A) tail and
      deadenylation of TE mRNA might be general mechanisms involved in the regulation
      of TE expression.

PMID- 22475420
TI  - Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) in riverine and
      estuarine sediments of the Pearl River Delta in southern China, with emphasis on
      spatial variability in diastereoisomer- and enantiomer-specific distribution of
      HBCD.
AB  - Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) were measured in
      surface sediments in the Pearl River Delta, southern China. The concentrations
      ranged from 0.06 to 304 ng/g dry weight for TBBPA and from 0.03 to 31.6 ng/g for
      total HBCD. The correlations between the TBBPA and HBCD concentrations were
      significant in rivers (Dongjiang, Zhujiang, Beijiang, and Dayanhe Rivers) with
      local input sources but not significant in the Xijiang River and Pearl River
      Estuary without local sources. HBCD was dominated by gamma-HBCD (averaged 52.5
      75.0%), whereas alpha-HBCD contributions were relatively high in sediments from
      the urban areas. The enantiomeric fractions of gamma-HBCD in the sediments
      (averaged from 0.431 +/- 0.035 to 0.479 +/- 0.010) differed significantly from
      that in HBCD technical product except for samples from the e-waste area (Dayanhe
      River, 0.488 +/- 0.091). This suggests that enantioselective biotransformation of
      HBCD occurs in the aquatic environment in this region.

PMID- 22475421
TI  - Nutrient fluxes between water column and sediments: potential influence of the
      pearl oyster culture.
AB  - This study quantifies benthic nutrient fluxes and sedimentation rates in the Ahe
      Atoll lagoon (French Polynesia), in two stations located under pearl oyster
      frames, and two control stations away from the pearl culture facility. Dissolved
      inorganic nitrogen fluxes ranged between 2 and 35 MUmol N m(-2) h(-1) and Soluble
      Reactive Phosphorus varied between -3 and 8.2 MUmol P m(-2) h(-1). Particulate
      sedimentation rates beneath the oysters were approximately five times higher than
      in the control zone and the percentage of small particles (<=63MUm) were about
      the twice. In contrast, sediment composition was similar under and outside the
      direct influence of oyster frames. In this ecosystem, where primary production is
      dependent on the available nitrogen, our study revealed that, while highly
      variable, benthic fluxes could sometimes contribute up to 28% of the nitrogen
      demand for primary production.

PMID- 22475422
TI  - Letter from the editors: Theranostics.

PMID- 22475423
TI  - Concepts, consequences, and implications of theranosis.
AB  - Although the term has been coined recently, the concepts underlying theranosis
      have been applied in patient care for more than one-half century. However,
      advanced technologies are used now. Theranosis describes processes used to tailor
      therapy for a patient. It is the use of diagnostic tests to identify those
      patients better-suited for a drug (or drugs) or to determine how well a drug is
      working. (131)I-iodide for imaging and for therapy of hyperthyroidism and thyroid
      cancer is an excellent example of personalized theranosis and has withstood
      challenge for more than 50 years. Radioimmunotherapy for non-Hodgkin lymphoma is
      a more recent example of theranosis. Either of 2 anti-CD20 monoclonal antibodies,
      one labeled with indium for imaging or (90)Y for radiotherapy or a second labeled
      with (131)I for both imaging and radiotherapy, is used for salvage and first-line
      therapy of multifocal non-Hodgkin lymphoma. The efficacy of these drugs is
      greater than that of alternative therapies. To mimic the molecular specificity
      and cell selectivity of a monoclonal antibody, smaller molecules that also bind
      to proteins upregulated by malignant cells can be used to transport cytotoxic
      agents to the malignant cells. Smaller carrier molecules like peptides, aptamers,
      affibodies, and selective, high-affinity ligands facilitate intensification of
      therapy because of their size. Personalized genomics, proteomics, and molecular
      imaging are among technologies currently used for theranosis. Molecular emission
      tomographic imaging with radiolabeled drugs has been used to examine the
      pharmacology of anticancer therapies and their effectiveness. Increased
      glycolysis, a molecular phenotype of many malignancies, can be imaged using (18)F
      fluoro-2-deoxyglucose (FDG). Tomographic imaging using FDG allows stratification
      of patients into those responding and likely to respond to the therapy and those
      better treated in another manner. Prediction of therapeutic response avoids
      useless therapy so that FDG imaging is included in official response evaluation
      criteria. Although a fixed approach to therapy may be more practical, an
      individualized approach is more likely to ensure that each patient receives an
      effective drug and drug dose that has acceptable and definable tissue effects.
      Drugs that work in one individual may be ineffective or cause adverse events in
      others.

PMID- 22475424
TI  - Paving the way to personalized medicine: production of some promising
      theragnostic radionuclides at Brookhaven National Laboratory.
AB  - This article reintroduces and reinforces our proposed paradigm that involves
      specific individual "dual-purpose" radionuclides or radionuclide pairs with
      emissions suitable for both imaging and therapy and which, when molecularly
      (selectively) targeted using appropriate carriers, would allow pretherapy low
      dose imaging as well as higher-dose therapy in the same patient. We have made an
      attempt to sort out and organize a number of such theragnostic radionuclides and
      radionuclide pairs that may thus potentially bring us closer to the age-long
      dream of personalized medicine for performing tailored low-dose molecular imaging
      (single-photon emission computed tomography/computed tomography or positron
      emission tomography/CT) to provide the necessary pretherapy information on
      biodistribution, dosimetry, the limiting or critical organ or tissue, the maximum
      tolerated dose, and so forth, followed by performing higher-dose targeted
      molecular therapy in the same patient with the same radiopharmaceutical.
      Beginning in the 1980s, our work at Brookhaven National Laboratory with such a
      "dual-purpose" radionuclide, tin-117m, convinced us that it is arguably one of
      the most promising theragnostic radionuclides, and we have continued to
      concentrate on this effort. Our results with this radionuclide are therefore
      covered in somewhat greater detail in this publication. A major problem that
      continues to be addressed, but remains yet to be fully resolved, is the lack of
      availability, in sufficient quantities, of a majority of the best candidate
      theragnostic radionuclides in a no-carrier-added form. A brief description of the
      recently developed new or modified methods at Brookhaven National Laboratory for
      the production of 5 theragnostic radionuclide/radionuclide pair items, whose
      nuclear, physical, and chemical characteristics seem to show great promise for
      personalized cancer and other therapies, is provided.

PMID- 22475425
TI  - Radioiodine: the classic theranostic agent.
AB  - Radioiodine has the distinction of being the first theranostic agent in our
      armamentarium. Millennia were required to discover that the agent in orally
      administered seaweed and its extracts, which had been shown to cure neck swelling
      due to thyromegaly, was iodine, first demonstrated to be a new element in 1813.
      Treatment of goiter with iodine began at once, but its prophylactic value to
      prevent a common form of goiter took another century. After Enrico Fermi produced
      the first radioiodine, (128)I, in 1934, active experimentation in the United
      States and France delineated the crucial role of iodine in thyroid metabolism and
      disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941,
      and thyroid cancer in 1943. After World War II, (131)I became widely available at
      a reasonable price for diagnostic testing and therapy. The rectilinear scanner of
      Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented
      by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of
      thyroid disease, with (131)I again the radioisotope of choice, although there
      were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I
      was first produced in 1949 but did not become widely available until about 1982,
      10 years after a production technique eliminated high-energy (124)I
      contamination. I continues to be the radioiodine of choice for the diagnosis of
      benign thyroid disease, whereas (123)I and (131)I are employed in the staging and
      detection of functioning thyroid cancer. (124)I, a positron emitter, can produce
      excellent anatomically correlated images employing positron emission
      tomography/computed tomography equipment and has the potential to enhance
      heretofore imperfect dosimetric studies in determining the appropriate
      administered activity to ablate/treat thyroid cancer. Issues of acceptable
      measuring error in thyroid cancer dosimetry and the role in (131)I therapy of
      tumor heterogeneity, tumor hypoxia, and kinetics must be overcome, and long-term
      outcome studies following (131)I given based on this new dosimetry must be
      completed before the nuclear medicine community will be able to predictably cure
      our thyroid cancer patients with this technology.

PMID- 22475426
TI  - Theranostics: evolution of the radiopharmaceutical meta-iodobenzylguanidine in
      endocrine tumors.
AB  - Since 1981, meta-iodobenzylguanidine (MIBG), labeled with (131)I and later
      (123)I, has become a valuable agent in the diagnosis and therapy of a number of
      endocrine tumors. Initially, the agent located pheochromocytomas and
      paragangliomas (PGLs), both sporadic and familial, in multiple anatomic sites;
      surgeons were thereby guided to excisional therapies, which were previously
      difficult and sometimes impossible. The specificity in diagnosis has remained
      above 95%, but sensitivity has varied with the nature of the tumor: close to 90%
      for intra-adrenal pheochromocytomas but 70% or less for PGLs. For patients with
      neuroblastoma, carcinoid tumors, and medullary thyroid carcinoma, imaging with
      radiolabeled MIBG portrays important diagnostic evidence, but for these
      neoplasms, use has been primarily as an adjunct to therapy. Although diagnosis by
      radiolabeled MIBG has been supplemented and sometimes surpassed by newer
      scintigraphic agents, searches by this radiopharmaceutical remain indispensable
      for optimal care of some patients. The radiation imparted by concentrations of
      (131)I-MIBG in malignant pheochromocytomas, PGLs, carcinoid tumors, and medullary
      thyroid carcinoma has reduced tumor volumes and lessened excretions of symptom
      inflicting hormones, but its value as a therapeutic agent is being fulfilled
      primarily in attacks on neuroblastomas, which are scourges of children. Much
      promise has been found in tumor disappearance and prolonged survival of treated
      patients. The experiences with therapeutic (131)I-MIBG have led to development of
      new tactics and strategies and to well-founded hopes for elimination of cancers.
      Radiolabeled MIBG is an exemplar of theranostics and remains a worthy agent for
      both diagnosis and therapy of endocrine tumors.

PMID- 22475427
TI  - FDG for therapy of metabolically active tumors.
AB  - (18)F-2-deoxy-2-fluoro-D-glucose ((18)F-FDG, later referred to as (19)FDG) has
      been extensively used in diagnostic positron emission tomography (PET) in
      oncology for many years. FDG is a glucose analog that is taken by cells in a
      similar fashion as glucose and is phosphorylated by hexokinase to (18)F-FDG-6
      phosphate but cannot undergo further glycolysis, and hence is trapped in the
      cell. Metastatic cancer remains a major cause of death men and women, surpassed
      only by heart disease. Despite the enormous research efforts resulting in
      emergence of novel drug candidates, there is little progress in improving the
      survival of patients with many types of solid tumors. Thus, novel therapies to
      combat metastatic cancer are urgently needed. With a physical half-life of almost
      2 hours, (18)F emits energetic positrons with high abundance (96%) and a path
      length in tissue of ~0.1-0.2 cm. Theoretically, these positrons can kill cancer
      cells in the same manner as electrons by damaging DNA and cellular machinery and
      inducing apoptosis/necrosis of the tumor cells. Several years ago, we explored,
      in a first series of comprehensive studies, the therapeutic potential of FDG in
      experimental breast cancer and showed its efficacy and safety. Since then, FDG
      therapy has been shown to be effective and safe in experimental melanoma, colon
      cancer, as well as in eliminating in vitro the endothelial cells in blood
      vessels, which supply the tumors with nutrients. The next step forward in
      translation of FDG therapy into the clinic should be a phase II clinical trial.
      Also, recent developments in targeted PET imaging could increase the range of PET
      pharmaceuticals potentially useful for positron therapy of metastatic cancers
      because of increased specificity of these tracers in comparison with FDG.

PMID- 22475428
TI  - Peptides and receptors in image-guided therapy: theranostics for neuroendocrine
      neoplasms.
AB  - Theranostics of neuroendocrine neoplasms (NENs) based on molecular imaging using
      receptor positron emission tomography/computed tomography (PET/CT) with (68)Ga
      labeled somatostatin (SMS) analogs and molecular radiotherapy applying peptide
      receptor radionuclide therapy (PRRNT) with (90)Y- and/or (177)Lu-labeled peptides
      has paved the way to personalized medicine. SMS receptor PET/CT enables very
      accurate detection of NENs and their metastases with high diagnostic sensitivity
      and specificity and provides quantitative, reproducible data that can be used for
      selecting patients for PRRNT and evaluation of therapy response. Among other
      advantages are the fast imaging protocol (total study time, 60-90 minutes), low
      radiation burden (10-12 mSv), flexibility in daily use, and lower cost than
      octreotide scintigraphy. As we move toward personalized medicine, the diagnostic
      information obtained from PET/CT must be improved, that is, by fast routine
      quantification of lesions. PRRNT is highly effective for the treatment of NENs,
      even in very advanced cases, and lends a benefit in overall survival of several
      years. In addition, significant improvement in clinical symptoms and excellent
      palliation can be achieved. In patients with progressive NENs, fractionated,
      personalized PRRNT with lower doses of radioactivity given over a longer period
      (Bad Berka Concept) results in good therapeutic responses. By this concept,
      severe hematologic and/or renal toxicity can be reduced or completely avoided,
      and the quality of life can be improved. Sequential (DUO-PRRNT) and concurrent
      (TANDEM-PRRNT) administrations of radiopeptides are more effective in progressive
      NEN than using either radionuclide alone. PRRNT should only be performed at
      specialized centers, as NEN patients need highly individualized interdisciplinary
      treatment and long-term care.

PMID- 22475429
TI  - Accuracy and precision of radioactivity quantification in nuclear medicine
      images.
AB  - The ability to reliably quantify activity in nuclear medicine has a number of
      increasingly important applications. Dosimetry for targeted therapy treatment
      planning or for approval of new imaging agents requires accurate estimation of
      the activity in organs, tumors, or voxels at several imaging time points. Another
      important application is the use of quantitative metrics derived from images,
      such as the standard uptake value commonly used in positron emission tomography
      (PET), to diagnose and follow treatment of tumors. These measures require
      quantification of organ or tumor activities in nuclear medicine images. However,
      there are a number of physical, patient, and technical factors that limit the
      quantitative reliability of nuclear medicine images. There have been a large
      number of improvements in instrumentation, including the development of hybrid
      single-photon emission computed tomography/computed tomography and PET/computed
      tomography systems, and reconstruction methods, including the use of statistical
      iterative reconstruction methods, which have substantially improved the ability
      to obtain reliable quantitative information from planar, single-photon emission
      computed tomography, and PET images.

PMID- 22475430
TI  - Acute and chronic watercress supplementation attenuates exercise-induced
      peripheral mononuclear cell DNA damage and lipid peroxidation.
AB  - Pharmacological antioxidant vitamins have previously been investigated for a
      prophylactic effect against exercise-induced oxidative stress. However, large
      doses are often required and may lead to a state of pro-oxidation and oxidative
      damage. Watercress contains an array of nutritional compounds such as beta
      carotene and alpha-tocopherol which may increase protection against exercise
      induced oxidative stress. The present randomised controlled investigation was
      designed to test the hypothesis that acute (consumption 2 h before exercise) and
      chronic (8 weeks consumption) watercress supplementation can attenuate exercise
      induced oxidative stress. A total of ten apparently healthy male subjects (age 23
      (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited
      to complete the 8-week chronic watercress intervention period (and then 8 weeks
      of control, with no ingestion) of the experiment before crossing over in order to
      compete the single-dose acute phase (with control, no ingestion). Blood samples
      were taken at baseline (pre-supplementation), at rest (pre-exercise) and
      following exercise. Each subject completed an incremental exercise test to
      volitional exhaustion following chronic and acute watercress supplementation or
      control. The main findings show an exercise-induced increase in DNA damage and
      lipid peroxidation over both acute and chronic control supplementation phases (P<
      0.05 v. supplementation), while acute and chronic watercress attenuated DNA
      damage and lipid peroxidation and decreased H2O2 accumulation following
      exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid
      soluble antioxidants (alpha-tocopherol, gamma-tocopherol and xanthophyll) was
      observed following watercress supplementation (P< 0.05 v. control) in both
      experimental phases. These findings suggest that short- and long-term watercress
      ingestion has potential antioxidant effects against exercise-induced DNA damage
      and lipid peroxidation.

PMID- 22475431
TI  - Dock7: a GEF for Rho-family GTPases and a novel myosin VI-binding partner in
      neuronal PC12 cells.
AB  - Myosin VI (MVI), the only known myosin that walks towards the minus end of actin
      filaments, is involved in several processes such as endocytosis, cell migration,
      and cytokinesis. It may act as a transporting motor or a protein engaged in actin
      cytoskeleton remodelling via its binding partners, interacting with its C
      terminal globular tail domain. By means of pull-down technique and mass
      spectrometry, we identified Dock7 (dedicator of cytokinesis 7) as a potential
      novel MVI-binding partner in neurosecretory PC12 cells. Dock7, expressed mainly
      in neuronal cells, is a guanine nucleotide exchange factor (GEF) for small
      GTPases, Rac1 and Cdc42, which are the major regulators of actin cytoskeleton.
      MVI-Dock7 interaction was further confirmed by co-immunoprecipitation of
      endogenous MVI complexed with Dock7. In addition, MVI and Dock7 colocalized in
      interphase and dividing cells. We conclude that in PC12 cells MVI-Dock7 complexes
      may function at different cellular locations during the entire cell cycle. Of
      note, MVI and Dock7 colocalized in primary culture hippocampal neurons also,
      predominantly in the outgrowths. We hypothesize that this newly identified
      interaction between MVI and Dock7 may help explain a mechanism for MVI-dependent
      regulation of actin cytoskeleton organization.

PMID- 22475432
TI  - Rationalization in meat cutting - consequences on physical workload.
AB  - Meat cutting is associated with several ergonomic risk factors and a high risk of
      musculoskeletal disorders. The development of new production systems points to an
      increased degree of mechanization; instead of subdividing split carcasses of pigs
      with a knife, the halves are trisected by an electrical saw into 'sixth-parts',
      resulting in shorter work cycles for the workers. Recently, machine-directed line
      production systems have been implemented. This study evaluates differences in the
      physical workload between the production systems. The postures and movements
      (inclinometry and goniometry) and muscular load (electromyography) of workers in
      the split-carcass- (five subjects), sixth-part- (ten) and line-production systems
      (five) were recorded. Most measures showed a statistically significant trend of
      declining physical exposure with increasing degrees of mechanization. For
      example, movement velocities of the upper arm were higher in the split-carcass
      system (50th percentile: mean 209 degrees /s) than in the sixth-part (103 degrees
      /s) and line production (81 degrees /s). However, the latter two were not
      statistically significantly different. A novel method for quantifying posture
      variation, based on inclinometry, showed that the split-carcass system implied
      the highest variation of the upper arm postures "within-minute" (i.e., a high
      range of motion each minute), but the lowest "between-minute" (i.e., a low
      variation during the course of the workday). In conclusion, the physical workload
      in the line-production system was significantly lower than in the split-carcass
      one, and tended also to be lower than in the sixth-part system. However, there
      may be disadvantages in line production, such as machine-directed work pace and
      shorter work cycles.

PMID- 22475433
TI  - The effect of load weight vs. pace on muscle recruitment during lifting.
AB  - The purpose of this study was to compare the effect on the trunk and upper
      extremity muscle recruitment when controlling the lifting pace and the lifting
      weight. Thirty nine healthy subjects performed a total of 12 lifts (3 lifting
      trials per condition, 2 lifting weights, and 2 lifting paces), from waist height
      to shoulder height. Kinematics of upper extremity and the box and
      electromyography of trunk and upper extremity muscles were collected. Temporal
      muscle recruitment pattern varied between muscles based on their function.
      Heavier lifting weight evenly increased the muscle recruitment throughout the
      lifting period without changing their temporal pattern. In contrary, lifting pace
      affected the temporal recruitment pattern in most of muscles. The faster lifting
      pace increased the muscle recruitment at the beginning phase but decreased at the
      terminal phase of lifting. It is important to educate the workers about the
      effect of lifting pace and weight on the biomechanical load to control the
      mechanical load on the muscles and spine.

PMID- 22475434
TI  - Transcriptional response of Atlantic salmon (Salmo salar) after primary versus
      secondary exposure to infectious salmon anemia virus (ISAV).
AB  - Following an infection with a specific pathogen, the acquired immune system of
      many teleostean fish, including salmonids, is known to retain a specific memory
      of the infectious agent, which protects the host against subsequent infections.
      For example, Atlantic salmon (Salmo salar) that have survived an infection with a
      low-virulence infectious salmon anemia virus (ISAV) isolate are less susceptible
      to subsequent ISAV infections. A greater understanding of the mechanisms and
      immunological components involved in this acquired protection against ISAV is
      fundamental for the development of efficacious vaccines and treatments against
      this pathogen. To better understand the immunity components involved in this
      observed resistance, we have used an Atlantic salmon DNA microarray to study the
      global gene expression responses of preexposed Atlantic salmon (fish having
      survived an infection with a low-virulence ISAV isolate) during the course of a
      secondary infection, 18 months later, with a high-virulence ISAV isolate. We
      present global gene expression patterns in both preexposed and naive fish,
      following exposure by either cohabitation with infected fish or by direct intra
      peritoneal injection of a high-virulence ISAV isolate. Our results show a clear
      reduction of ISAV viral loads in head-kidney of secondary infected fish compared
      to primary infected fish. Further, we note a lower-expression of many antiviral
      innate immunity genes in the secondary infected fish, such as the interferon
      induced GTP-binding protein Mx, CC-chemokine 19 and signal transducer and
      activator of transcription 1 (STAT 1), as well as MHC class I antigen
      presentation involved genes. Potential acquired immunity genes such as GILT,
      leukocyte antigen transcript CD37 and Ig mu chain C region membrane-bound form
      were observed to be over-expressed in secondary infected fish. The observed
      differential gene expression profile in secondary and primary infected fish head
      kidney provides great insight into immunity components involved during primary
      and secondary ISAV infection.

PMID- 22475435
TI  - Does steroid sulfatase deficiency influence postpartum psychosis risk?
AB  - Postpartum (or puerperal) psychosis (PP) occurs shortly after childbirth in 0.1
      0.2% of women, and is characterised by delusions, mood swings, confused thinking,
      and disorganised behaviour. The condition is disturbing for patients and their
      family members and loved ones, and affected individuals may be at increased risk
      of harming themselves or their offspring. The features of PP indicate a
      substantial biological basis to its pathogenesis, although currently little is
      known about possible risk factors. Based on recent results from animal model and
      human studies, I propose that reduced function of the enzyme steroid sulfatase in
      the mother represents a unifying and physiologically plausible candidate
      mechanism for the neural and endocrinological disturbances seen in cases of PP.

PMID- 22475436
TI  - Mass transfer model of triethylamine across the n-decane/water interface derived
      from dynamic interfacial tension experiments.
AB  - This publication presents a detailed experimental and theoretical study of mass
      transfer of triethylamine (TEA) across the n-decane/water interface. In
      preliminary investigations, the partition of TEA between n-decane and water is
      determined. Based on the experimental finding that the dissociation of TEA takes
      place in the aqueous and in the organic phase, we assume that the interfacial
      mass transfer is mainly affected by adsorption and desorption of ionized TEA
      molecules at the liquid/liquid interface. Due to the amphiphilic structure of the
      dissociated TEA molecules, a dynamic interfacial tension measurement technique
      can be used to experimentally determine the interfacial mass transport. A model
      based approach, which accounts for diffusive mass transport in the finite liquid
      bulk phases and for adsorption and desorption of ionized TEA molecules at the
      interface, is employed to analyze the experimental data. In the equilibrium
      state, the interfacial tension of dissociated TEA at the n-decane/water interface
      can be adequately described by the Langmuir isotherm. The comparison between the
      theoretical and the experimental dynamic interfacial tension data reveals that an
      additional activation energy barrier for adsorption and desorption at the
      interface has to be regarded to accurately describe the mass transport of TEA
      from the n-decane phase into the aqueous phase. Corresponding adsorption rate
      constants can be obtained by fitting the theoretical predictions to the
      experimental data. Interfacial tension measurements of mass transfer from the
      aqueous into the organic phase are characterized by interfacial instabilities
      caused by Marangoni convection, which result in an enhancement of the transfer
      rate across the interface.

PMID- 22475437
TI  - [Clinical usefulness of three quantitative D-dimers tests in outpatients with
      suspected deep vein thrombosis].
AB  - BACKGROUND AND OBJECTIVE: The diagnostic approach in outpatients with suspected
      deep vein thrombosis (DVT) of the lower limbs includes D-dimer measurement (DD).
      Elevated DD is not a diagnostic value for DVT. However, a normal value
      contributes to ruling out DVT. We do not know the best method to determine DD.
      Therefore, we have analyzed the clinical utility of three quantitative assays to
      determine DD in outpatients with suspected DVT. PATIENTS AND METHODS: Consecutive
      outpatients with suspected DVT of the lower limbs who were referred to the DVT
      medical consultation were enrolled in the study. We used a diagnostic algorithm
      that included determining the pretest clinical probability (PCP) (Wells scale),
      DD level using three different quantitative methods (ELISA mini-VIDAS((r)), Acure
      care DDMR and DD-Plus). The DVT diagnosis was confirmed by seriated compression
      ultrasonography of the lower limbs. We analyzed the concordance between the three
      analytic methods to quantify DD and the characteristics. RESULTS: A total of 306
      patients (mean age 60 years, 62% women) with suspected DVT of the lower limbs
      were included. The compression ultrasonography confirmed the diagnosis of DVT in
      23.8% of the patients. Anticoagulation treatment was not performed in patients in
      whom DVT was ruled out, and no thromboembolic event occurred during the 3 months
      of follow-up. The best concordance test results were between ELISA mini
      VIDAS((r)) and Acure-care DDMR assays. Both assays demonstrated elevated
      sensibility and a negative predictive value. ELISA mini-VIDAS((r)) was the best
      analytic method for the subgroup of patients with low clinical probability.
      CONCLUSIONS: The ELISA mini-VIDAS((r)) method to determine DD rules out DVT in
      patients with low clinical probability.

PMID- 22475438
TI  - Management of heparin-induced thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a rare but severe
      prothrombotic adverse effect of heparin treatment. The underlying cause is the
      formation of highly immunogenic complexes between negatively charged heparin and
      positively charged platelet factor 4 (PF4). Resulting antibodies against these
      PF4/heparin complexes can activate platelets via the platelet FcgammaIIa
      receptor, leading to thrombin generation and thus to the paradox of a
      prothrombotic state despite thrombocytopenia and application of heparin. Prompt
      diagnosis of HIT is important in order to change treatment to prevent severe
      thromboembolic complications. However, this is often difficult as
      thrombocytopenia is frequent in hospitalized patients and the commercially
      available laboratory tests for HIT antibodies have a high negative predictive
      value but only a poor positive predictive value. This leads to overdiagnosis and
      overtreatment of HIT, which also bear the risk for adverse outcomes. AREAS
      COVERED: This review aims at resuming recent data on HIT, thereby focusing on the
      role of new anticoagulants and providing a framework for diagnosis and treatment.
      Furthermore, it provides some insights into the pathogenesis of this peculiar
      adverse drug reaction and ventures a guess at its future relevance in clinical
      practice. EXPERT OPINION: New drugs which are strongly negatively charged should
      be assessed for their capacity to form complexes with PF4. If they do so, they
      bear the risk of inducing a HIT-like immune response. The immunology of HIT is
      still largely unresolved. Understanding HIT might provide insights into other
      immune and autoimmune response mechanisms.

PMID- 22475439
TI  - Would you consent to being examined by a medical student? Western Australian
      general public survey.
AB  - BACKGROUND: Patients generally have positive attitudes regarding being examined
      by a supervised medical student as part of their medical care. However, it is
      difficult to obtain model patients for students to examine purely for teaching
      purposes (i.e. in the absence of medical treatment). AIMS: This study explored
      the effects of participants' demographics, characteristics of medical students,
      and the type of examination/procedure on whether individuals would consent to be
      examined by a medical student purely for teaching purposes. METHOD: Four-hundred
      and-two Western Australians completed an online survey in 2009. RESULTS:
      Individuals were generally unconcerned regarding a medical student's gender and
      ethnicity. However, they would either not permit or wanted more advanced medical
      students to examine more intimate body regions and conduct more invasive
      procedures. Less observing medical students were permitted to be present for
      intimate examinations. Individuals who were male, aged>=25 years, Caucasian, and
      of no religious affiliation were more likely to permit formative year medical
      students to examine and conduct procedures on them. Additionally, these
      individuals were more likely to have had prior experience with a medical student
      and/or been hospitalised previously. CONCLUSIONS: This information may be useful
      in terms of recruiting patient models for teaching purposes.

PMID- 22475440
TI  - Unique presentation of a giant mediastinal tumor as kyphosis: a case report.
AB  - INTRODUCTION: Although posture distortion is a common problem in elderly
      patients, spinal deformity caused by a thymoma has not been previously reported.
      Thymomas are slowly growing tumors that predominantly cause respiratory symptoms.
      CASE PRESENTATION: We report the case of an 83-year-old woman who was admitted
      with a giant mediastinal mass that had caused progressive spinal distortion and
      weight loss to our department. The clinical and laboratory investigations that
      followed revealed one of the largest thymomas ever reported in the medical
      literature, presenting as a mass lesion placed at the left hemithorax. She
      underwent complete surgical excision of the tumor via a median sternotomy. Two
      years after the operation, she showed significant improvement in her posture, no
      pulmonary discomfort, and a gain of 20 kg; she remains disease free based on
      radiographic investigations. CONCLUSIONS: In this case, a chronic asymmetric load
      on the spine resulted in an abnormal vertebral curvature deformity that presented
      as kyphosis.

PMID- 22475441
TI  - Short-term fibronectin treatment induces endothelial-like and angiogenic
      properties in monocyte-derived immature dendritic cells: involvement of
      intracellular VEGF and MAPK regulation.
AB  - Fibronectin (FN) is an extracellular matrix protein promoting cell proliferation,
      adhesion, and survival and is localized in the intimal layer of normal and
      atherosclerotic blood vessels. Dendritic cells (DCs) are potent antigen
      presenting cells located in healthy and diseased intima, and thus may predispose
      arteries to atherosclerosis. Besides their pro-atherogenic activities DCs can
      promote neovascularization, by releasing pro-angiogenic mediators and/or by trans
      differentiating into endothelial-like cells. Here, we investigated changes in
      morphology, function and angiogenic properties of monocyte-derived immature DCs
      (Mo-iDCs) after a short-term FN treatment and some of the signaling pathways
      involved in these processes. The cells were analyzed by time-lapse, confocal
      microscopy and flow cytometry. Within 90 min of re-plating, FN induced a swift
      morphologic transformation of most round iDCs into spindle-shaped iDCs (sp-iDCs).
      This was characterized by redistribution of mitochondria into dendritic spindles,
      decreased CD1c, and increased thrombomodulin (CD141) expression. Functionally, sp
      iDCs acquired Ulex-europaeus-agglutinin-1 lectin binding, phagocytosis was
      decreased and intracellular (nuclear and cytosolic) vascular endothelial growth
      factor (VEGF) was increased. FN also induced ERK1/2 phosphorylation in round
      iDCs, and p38MAPK phosphorylation in sp-iDCs. Inhibiting p38MAPK, but not ERK1/2,
      restrained the FN-induced transformation into sp-iDCs. Furthermore, FN-treatment
      of Mo-iDCs induced a paracrine angiogenic effect on endothelial tube formation,
      which was abolished by inhibiting ERK1/2 or VEGF. Inhibiting p38MAPK had no
      effect on endothelial tube formation. By contrast, in laminin-treated Mo-iDCs,
      which had round-shaped morphology, CD1c and CD141 expression was similar to
      control untreated cells, but intracellular VEGF levels were higher, and
      endothelial tube formation was an individual trait. We conclude that a short-term
      FN treatment induced angiogenic intracrine and paracrine properties in Mo-iDCs.
      This may act as an immediate protective mechanism to maintain vascular
      homeostasis. Moreover, inducing sp-iDCs by short term FN-treatment or ERK1/2
      modulation might be considered as new approaches for regulating angiogenesis
      through the production/inhibition of pro-angiogenic mediators. Collectively,
      these findings may support a role for FN and Mo-iDCs in vascular function and
      angiogenesis.

PMID- 22475442
TI  - Dosimetric comparison of metastatic spinal photon treatment techniques.
AB  - Traditional palliative treatment of metastatic cancer to the vertebral bodies
      often results in doses to the spinal cord that are higher than the dose
      prescribed to the target, or gross tumor volume (GTV). This study compares
      traditional techniques of spine palliation with intensity-modulated radiation
      therapy (IMRT). The purpose of the study is 2-fold: first, the study demonstrates
      the benefits of using IMRT to lower the dose to the organs at risk (OAR),
      particularly for the spinal cord and other nonspecified normal tissues; second,
      the article provides information regarding the advantages and disadvantages of
      commonly used conventional techniques for treating the vertebral bodies based on
      patient anatomy. Because the use of IMRT or other advanced techniques may be
      prohibitive because of insurance issues, treatment plans were created that
      compared optimal coverage vs. optimal sparing for single-field, wedged-pair, and
      opposed-beam arrangements. Fifty-five patients were selected and divided by
      location of target (cervical, thoracic, and lumbar spine) and also by the
      measured separation between the anterior and posterior surface of the patient at
      the level of mid-GTV. Within each anatomic category the patients again were
      divided into the categories of small, medium, and large based on separation. The
      patient dataset that most closely represented the average separation within each
      category was selected, resulting in a total of 9 patients, and the appropriate
      treatment plan techniques were calculated for each of the 9 patients. The results
      of the study do show that the use of IMRT is far superior when compared with
      other techniques, both for coverage and for sparing of the surrounding tissue,
      regardless of patient size and the section of spine being treated. Based on a
      combination of both target coverage and sparing of normal tissues, the
      conventional plan of choice may vary by both the section of spine to be treated
      and by the size of the patient.

PMID- 22475443
TI  - Functional aspects of distal oesophageal spasm: the role of onset velocity and
      contraction amplitude on bolus transit.
AB  - BACKGROUND: Distal oesophageal spasm is a rare and under-investigated motility
      abnormality. Recent studies indicate effective bolus transit in varying
      percentages of distal oesophageal spasm patients. AIM: Explore functional aspects
      including contraction onset velocity and contraction amplitude cut-off values for
      simultaneous contractions to predict complete bolus transit. METHODS: We re
      examined data from 107 impedance-manometry recordings with a diagnosis of distal
      oesophageal spasm. Receiver operating characteristic analysis was conducted,
      regarding effects of onset velocity on bolus transit taking into account distal
      oesophageal amplitude and correcting for intra-individual repeated measures.
      RESULTS: Mean area under the receiver operating characteristic curve for saline
      and viscous swallows were 0.84+/-0.05 and 0.84+/-0.04, respectively. Velocity
      criteria of >30 cm/s when distal oesophageal amplitude>100 mmHg and 8 cm/s when
      distal oesophageal amplitude<100 mmHg for saline and 32cm/s when distal
      oesophageal amplitude>100 mmHg and >7 cm/s when distal oesophageal amplitude<100
      mmHg for viscous had a sensitivity of 75% and specificity of 80% to identify
      complete bolus transit. Using these criteria, final diagnosis changed in 44.9% of
      patients. Abnormal bolus transit was observed in 50.9% of newly diagnosed distal
      oesophageal spasm patients versus 7.5% of patients classified as normal. Distal
      oesophageal spasm patients with distal oesophageal amplitude>100 mmHg suffered
      twice as often from chest pain than those with distal oesophageal amplitude<100
      mmHg. CONCLUSION: The proposed velocity cut-offs for diagnosing distal
      oesophageal spasm improve the ability to identify patients with spasm and
      abnormal bolus transit.

PMID- 22475444
TI  - Friendship 2.0: adolescents' experiences of belonging and self-disclosure online.
AB  - This study explores the role that digital media technologies play in adolescents'
      experiences of friendship and identity. The author draws on findings from in
      depth interviews with 32 adolescents (15 girls, 17 boys) ages 13-18 (M = 15.5
      years) attending one of seven secondary schools in Bermuda. The adolescents were
      asked to describe the nature of their online exchanges with friends and the value
      they ascribe to these conversations. A thematic analysis of their responses
      revealed that online peer communications promote adolescents' sense of belonging
      and self-disclosure, two important peer processes that support identity
      development during adolescence. At the same time, the unique features of computer
      mediated communication shape adolescents' experiences of these processes in
      distinct ways. Gender and age differences show that adolescents' online peer
      communications are not uniform; the characteristics that distinguish adolescents
      offline also shape their online activities.

PMID- 22475445
TI  - What actually makes bullying stop? Reports from former victims.
AB  - School bullying is a serious, worldwide problem which is not easily counteracted.
      The present study focuses on the perspective of former victims, asking them what
      it was that made the bullying stop in their case. Participants were 273 18-year
      old former victims in Sweden, a country in which schools are doing extensive work
      against bullying and the bullying prevalence is relatively low. Results showed
      that although support from school personnel was the most common reason that the
      former victims gave to why the bullying had ended, it was only mentioned by a
      fourth of them. In fact, it was almost equally as common that the bullying had
      ended in that the victims transitioned to a new school level or changed their way
      of coping with the bullying. Very few of the adolescents reported that the
      bullying had stopped due to support from peers.

PMID- 22475446
TI  - Novel therapies in acute and chronic heart failure.
AB  - Despite past advances in the pharmacological management of heart failure, the
      prognosis of these patients remains poor, and for many, treatment options remain
      unsatisfactory. Additionally, the treatments and clinical outcomes of patients
      with acute decompensated heart failure have not changed substantially over the
      past few decades. Consequently, there is a critical need for new drugs that can
      improve clinical outcomes. In the setting of acute heart failure, new inotrops
      such as cardiac myosin activators and new vasodilators such as relaxin have been
      developed. For chronic heart failure with reduced ejection fraction, there are
      several new approaches that target multiple pathophysiological mechanism
      including novel blockers of the renin-angiotensin-aldosterone system (direct
      renin inhibitors, dual-acting inhibitors of the angiotensin II receptor and
      neprilysin, aldosterone synthase inhibitors), ryanodine receptor stabilizers, and
      SERCA activators. Heart failure with preserved ejection fraction represents a
      substantial therapeutic problem as no therapy has been demonstrated to improve
      symptoms or outcomes in this condition. Newer treatment strategies target
      specific structural and functional abnormalities that lead to increased
      myocardial stiffness. Dicarbonyl-breaking compounds reverse advanced glycation
      induced cross-linking of collagen and improve the compliance of aged and/or
      diabetic myocardium. Modulation of titin-dependent passive tension can be
      achieved via phosphorylation of a unique sequence on the extensible region of the
      protein. This review describes the pathophysiological basis, mechanism of action,
      and available clinical efficacy data of drugs that are currently under
      development. Finally, new therapies for the treatment of heart failure
      complications, such as pulmonary hypertension and anemia, are discussed.

PMID- 22475447
TI  - Validation of reference genes for ovarian tissue from capuchin monkeys (Cebus
      apella).
AB  - There is no tradition in studies reporting the effect of exposure to
      cryoprotectants or simply hypoxia and hypothermia on gene expression in the
      ovarian tissue and there has been only one study on reference or target genes
      quantification, and comparisons of normoxic with hypoxic, hypothermic and toxic
      conditions. Our aim in the present study was to investigate the stability of
      three reference genes in the ovarian tissue of capuchin monkeys (Cebus apella).
      To this end, fresh and cryoprotectant-exposed ovarian biopsies were used. Both
      fresh and exposed ovarian tissues were subjected to total RNA extraction and
      synthesis of cDNA. cDNA was amplified by real-time polymerase chain reaction
      (PCR), and GeNorm, BestKeeper and NormFinder software were used to evaluate the
      stability of glyceraldehyde-2-phosphate dehydrogenase (GAPDH), hypoxanthine
      phosphoribosyltransferase 1 (HPRT1) and TATA-binding protein (TBP). Results
      demonstrated that, in the ovarian tissue from capuchin monkeys, HPRT1 and TBP
      were the most suitable reference genes and thus could be used as parameters to
      normalize data in future studies. In contrast, GAPDH appeared as the least stable
      gene among the tested reference genes. In conclusion, HPRT1 and TBP were the most
      stable reference genes in fresh and cryoprotectant-exposed ovarian tissue from
      capuchin monkeys.

PMID- 22475448
TI  - Engineered antibody approaches for Alzheimer's disease immunotherapy.
AB  - The accumulation of amyloid-beta-peptide (Abeta or A-beta) in the brain is
      considered to be a key event in the pathogenesis of Alzheimer's disease (AD).
      Over the last decade, antibody strategies aimed at reducing high levels of Abeta
      in the brain and or neutralizing its toxic effects have emerged as one of the
      most promising treatments for AD. Early approaches using conventional antibody
      formats demonstrated the potential of immunotherapy, but also caused a range of
      undesirable side effects such meningoencephalitis, vasogenic edema or cerebral
      microhemorrhages in both murine and humans. This prompted the exploration of
      alternative approaches using engineered antibodies to avoid adverse immunological
      responses and provide a safer and more effective therapy. Encouraging results
      have been obtained using a range of recombinant antibody formats including,
      single chain antibodies, antibody domains, intrabodies, bispecific antibodies as
      well as Fc-engineered antibodies in transgenic AD mouse and primate models. This
      review will address recent progress using these recombinant antibodies against
      Abeta, highlighting their advantages over conventional monoclonal antibodies and
      delivery methods.

PMID- 22475449
TI  - Structural evidence for conformational changes of Delta class glutathione
      transferases after ligand binding.
AB  - We report four new crystal structures for Delta class glutathione transferases
      from insects. We compare these new structures as well as several previously
      reported structures to determine that structural transitions can be observed with
      ligand binding. These transitions occurred in the regions around the active site
      entrance, including alpha helix 2, C-terminus of alpha helix 4 including the loop
      to helix 5 and the C-terminus of helix 8. These structural movements have been
      reported or postulated to occur for several other glutathione transferase
      classes; however, this is the first report showing structural evidence of all
      these movements occurring, in this case in Delta class glutathione transferases.
      These fluctuations also can be observed occurring within a single structure as
      there is ligand bound in only one subunit and each subunit is undergoing
      different conformational transitions. The structural comparisons show
      reorganizations occur both pre- and post-GSH ligand binding communicated through
      the subunit interface of the quaternary assembly. Movements of these positions
      would allow 'breathing' of the active site for substrate entrance, topological
      rearrangement for varying substrate specificity and final product release.

PMID- 22475450
TI  - Autophagy in the intestinal epithelium regulates Citrobacter rodentium infection.
AB  - Autophagy, a ubiquitous degradation pathway, is important for the survival and
      homeostasis of cells. Previous studies have demonstrated the role of autophagy in
      host defense against bacterial infection, but the importance of autophagy in the
      intestinal epithelium for the regulation of bacterial infection has not been
      fully elucidated. In this study, we showed that the essential autophagy protein
      Atg7 is required for resistance to Citrobacter rodentium infection in the
      intestinal epithelium. Infected mice in which Atg7 had been conditionally deleted
      from the intestinal epithelium exhibited greater clinical evidence of disease and
      higher expression levels of pro-inflammatory cytokine mRNA in the large
      intestine. Moreover, C. rodentium clearance was reduced in the Atg7 conditional
      knockout mice. These results demonstrate that autophagy in intestinal epithelial
      cells plays an important role in host defense against C. rodentium infection and
      the regulation of C. rodentium infectious colitis.

PMID- 22475451
TI  - Targeting mTOR pathways in human malignancies.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is a protein kinase involved
      in the phosphatidylinositol 3-Kinase (PI3K)/AKT signalling pathway with a central
      role in the control of cell growth, survival and angiogenesis. Multiple and
      frequent dysregulations of this pathway in human tumors make it a central target
      in the development of new anticancer treatments. OBJECTIVE: To review the most
      significant data on mTOR pathway, role of mTOR inhibitors in cancer treatment,
      preclinical and clinical data of the three first generation mTOR inhibitors
      (temsirolimus, everolimus and deferolimus), rationales, preclinical and clinical
      data of second generation mTOR inhibitors. METHODS: Review of published
      literature on mTOR and related pathways, rapalogs and novel mTOR inhibitors.
      RESULTS/CONCLUSIONS: Temsirolimus and everolimus have been approved for the
      treatment of metastatic Renal Cell Carcinoma (RCC), temsirolimus also for Mantle
      Cell Lymphoma (MCL) and everolimus will be approved for pancreatic neuroendocrine
      tumors; all three rapalogs are currently evaluated in phase III studies in
      several tumors. Only limited published data are available on new mTOR inhibitors;
      however, in vitro and in vivo in preclinical studies they have shown a
      significant antiproliferative activity against a broad panel of tumors and a
      favourable safety profile, with disease stabilization or even tumor regression,
      either as single agent or in combination.

PMID- 22475452
TI  - Iodine status and fish intake of Sudanese schoolchildren living in the Red Sea
      and White Nile regions.
AB  - OBJECTIVE: To investigate iodine status and fish consumption of schoolchildren
      living in the Red Sea and White Nile regions of Sudan. DESIGN: Cross-sectional
      study to determine urinary iodine concentration, visible goitre rate, iodine
      content of salt and fish consumption. SETTING: Port Sudan (Red Sea) and Jabal
      Awliya (White Nile), Sudan. SUBJECTS: Two hundred eighty (n 280) children aged 6
      12 years (142 boys, 138 girls). RESULTS: The median urinary iodine concentration
      in children from Port Sudan and Jabal Awliya was 553 and 160 MUg/l, respectively.
      Goitre was detected in 17.1 % of children from Port Sudan but only in 1.4 % from
      Jabal Awliya, The salt samples from Port Sudan contained 150-360 mg iodine
      (KOI3)/kg salt, whereas those from Jabal Awliya had levels below the detection
      limit. Despite consuming salt devoid of iodine, children from Jabal Awliya had
      optimal iodine status. It is plausible that consumption of Nile fish from Jabal
      Awliya Reservoir, which is a good source of iodine and favoured by the locals,
      might have provided sufficient iodine. In contrast, children from Port Sudan were
      at higher risk of iodine-induced hyperthyroidism resulting from consumption of
      excessively iodised salt. CONCLUSIONS: The findings of the study clearly
      demonstrated that (i) Sudan still has a problem with iodine nutrition and quality
      control and monitoring of salt iodisation and (ii) including fish in the diet
      could provide a sufficient amount of iodine for schoolchildren.

PMID- 22475453
TI  - CT mapping of saline distribution after infusion of saline into the liver in an
      ex vivo animal model. How much tissue is actually infused in an image-guided
      procedure?
AB  - PURPOSE: To track the saline during infusion with a 15 G needle into healthy pig
      livers at high and low infusion rates for 300 s. METHODS: In each experiment, the
      needle was inserted into a single lobe of the liver to a depth of at least 2 cm
      following its longer axis. Two sets of experiments were defined: 1) low infusion
      rate of 0.1 mL/min (n = 6) and 2) high infusion rate of 1 mL/min (n = 6). Cine CT
      scans were carried out and three transverse planes were defined around the
      infusion point (IP), which corresponds with needle tip. Two assessments were
      performed: 1) a dynamic plane study focused on the time progress of the saline
      distribution on a single plane, which provided the Mean Percentage of Grayscale
      Intensity (MPGI); and 2) a volumetric study focused on the three dimensional
      distribution of the saline around IP at the end of the experiment, which provided
      the High Intensity Volume Ratio (HIVR). RESULTS: The saline solution was
      conspicuous around the IP and shortly after heterogeneously inside the vessels.
      At the high infusion rate, the saline became conspicuous not only much sooner
      (evident at 20 s) but farther away (mean value of MPGI over 2%, up to 17 mm from
      the IP) and at a much higher intensity (mean value of MPGI over 10% up to 4 mm
      from the IP). The lower the radial distance to the IP, the greater the difference
      in HIVR between both groups. CONCLUSIONS: The high infusion rate leads to a
      faster, wider and a more marked presence of saline than the low rate. The rapid
      drainage into the hepatic veins may explain the heterogeneous distribution.

PMID- 22475454
TI  - Concentration modulated skin marker for radiotherapy treatment planning process.
AB  - BACKGROUND AND PURPOSE: For conformal radiotherapy, it is feasible to achieve
      high accuracy in contouring the outline of the target volume in treatment
      planning process. In contouring process, target volume is occasionally defined by
      means of either surgical clips or skin marker during patient anatomical data
      acquisition. Treatment planning systems are predicting invalid radiation dose
      distributions by using surgical clips and skin marker within the patient. Purpose
      of this study is the production of new skin marker which affects less dose
      distributions of electron beam. MATERIALS AND METHODS: The influences of lead and
      commercial markers on dose calculations in a 3D treatment planning systems were
      investigated in terms of electron beam energy and dose profile depth. Dose
      deviation with commercial marker was observed to smaller than lead marker.
      However this dose deviation was still at big value. In order to reduce of this
      value, barium sulfate suspension and ultrasound gel were mixed with different
      volumetric ratio. With the purpose of acception the most suitable marker for
      radiation therapy, obtained new suspensions were investigated in terms of
      visibility and dose deviation. RESULTS: B:G/1:10 marker was determined to cause
      optimum visibility and the lowest dose deviation on dose calculations in terms of
      electron beam energy and dose profile depth. CONCLUSIONS: Appropriate marker,
      mixture of substances such as barium sulfate suspension and ultrasound gel can be
      produced. This marker is both ease of usage and practical and economical. Each
      clinic can prepare marker which is peculiar to suspension with different
      concentration of substance for specific visibility. But, it should be taken into
      account resultant dose deviation to beam calculation depending on barium sulfate
      concentration.

PMID- 22475455
TI  - Design and synthesis of skeletal analogues of gambierol: attenuation of amyloid
      beta and tau pathology with voltage-gated potassium channel and N-methyl-D
      aspartate receptor implications.
AB  - Gambierol is a potent neurotoxin that belongs to the family of marine polycyclic
      ether natural products and primarily targets voltage-gated potassium channels
      (K(v) channels) in excitable membranes. Previous work in the chemistry of marine
      polycyclic ethers has suggested the critical importance of the full length of
      polycyclic ether skeleton for potent biological activity. Although we have
      previously investigated structure-activity relationships (SARs) of the peripheral
      functionalities of gambierol, it remained unclear whether the whole polycyclic
      ether skeleton is needed for its cellular activity. In this work, we designed and
      synthesized two truncated skeletal analogues of gambierol comprising the EFGH-
      and BCDEFGH-rings of the parent compound, both of which surprisingly showed
      similar potency to gambierol on voltage-gated potassium channels (K(v))
      inhibition. Moreover, we examined the effect of these compounds in an in vitro
      model of Alzheimer's disease (AD) obtained from triple transgenic (3xTg-AD) mice,
      which expresses amyloid beta (Abeta) accumulation and tau hyperphosphorylation.
      In vitro preincubation of the cells with the compounds resulted in significant
      inhibition of K(+) currents, a reduction in the extra- and intracellular levels
      of Abeta, and a decrease in the levels of hyperphosphorylated tau. In addition,
      pretreatment with these compounds reduced the steady-state level of the N-methyl
      D-aspartate (NMDA) receptor subunit 2A without affecting the 2B subunit. The
      involvement of glutamate receptors was further suggested by the blockage of the
      effect of gambierol on tau hyperphosphorylation by glutamate receptor
      antagonists. The present study constitutes the first discovery of skeletally
      simplified, designed polycyclic ethers with potent cellular activity and
      demonstrates the utility of gambierol and its synthetic analogues as chemical
      probes for understanding the function of K(v) channels as well as the molecular
      mechanism of Abeta metabolism modulated by NMDA receptors.

PMID- 22475456
TI  - Inverse opal carbons for counter electrode of dye-sensitized solar cells.
AB  - We investigated the fabrication of inverse opal carbon counter electrodes using a
      colloidal templating method for DSSCs. Specifically, bare inverse opal carbon,
      mesopore-incoporated inverse opal carbon, and graphitized inverse opal carbon
      were synthesized and stably dispersed in ethanol solution for spray coating on a
      FTO substrate. The thickness of the electrode was controlled by the number of
      coatings, and the average relative thickness was evaluated by measuring the
      transmittance spectrum. The effect of the counter electrode thickness on the
      photovoltaic performance of the DSSCs was investigated and analyzed by
      interfacial charge transfer resistance (R(CT)) under EIS measurement. The effect
      of the surface area and conductivity of the inverse opal was also investigated by
      considering the increase in surface area due to the mesopore in the inverse opal
      carbon and conductivity by graphitization of the carbon matrix. The results
      showed that the FF and thereby the efficiency of DSSCs were increased as the
      electrode thickness increased. Consequently, the larger FF and thereby the
      greater efficiency of the DSSCs were achieved for mIOC and gIOC compared to IOC,
      which was attributed to the lower R(CT). Finally, compared to a conventional Pt
      counter electrode, the inverse opal-based carbon showed a comparable efficiency
      upon application to DSSCs.

PMID- 22475457
TI  - Coumarin-based drugs: a patent review (2008 -- present).
AB  - INTRODUCTION: Coumarins are a group of plant-derived polyphenolic compounds. They
      belong to the benzopyrones family and possess a wide variety of cytoprotective
      and modulatory functions, which may be translated to therapeutic potentials for
      multiple diseases. Their physicochemical properties seem to define the extent of
      the biological activity. AREAS COVERED: In this review recent patent publications
      (2008 - 2011), describing coumarins and their derivatives, are analyzed.
      Synthesis, combinatorial techniques, biological evaluation in vitro/in vivo/ex
      vivo, e.g. antimitotic, immunomodulating, antiviral, anticancer and cytotoxic
      agents, as well as some new biological assays, are included. In addition to
      selected biological data, a wide range of pharmaceutical applications and
      pharmaceutical compositions are also summarized. EXPERT OPINION: Several natural
      and synthetic coumarins and derivatives with potent in vivo/in vitro biological
      responses appear to be promising anticancer activities. Their clinical evaluation
      will be critical to assess therapeutic utility. The compounds for which the
      mechanism of action is well defined can serve as lead compounds for the design of
      new more promising molecules.

PMID- 22475458
TI  - Variations in hospital standardised mortality ratios (HSMR) as a result of
      frequent readmissions.
AB  - BACKGROUND: We investigated the impact that variations in the frequency of
      readmissions had upon a hospital's standardised mortality ratio (HSMR). An
      adapted HSMR model was used in the study. Our calculations were based on the
      admissions of 70 hospitals in The Netherlands during the years 2005 to 2009.
      METHODS: Through a retrospective analysis of routinely collected hospital data,
      we calculated standardised in-hospital mortality ratios both by hospital and by
      diagnostic group (H/SMRs) using two different models. The first was the Dutch
      2010 model while the second was the same model but with an additional adjustment
      for the readmission frequency. We compared H/SMR outcomes and the corresponding
      quality metrics in order to test discrimination (c-statistics), calibration
      (Hosmer-Lemeshow) and explanatory power (pseudo-R2 statistic) for both models.
      RESULTS: The SMR outcomes for model 2 compared to model 1, varied between -39%
      and +110%. On the HSMR level these variations ranged from -12% to +11%. There was
      a substantial disagreement between the models with respect to significant death
      on the SMR level as well as the HSMR level (~ 20%). All quality metrics comparing
      both models were in favour of model 2. The susceptibility to adjustment for
      readmission increased for longer review periods. CONCLUSIONS: The 2010 HSMR model
      for the Netherlands was sensitive to adjustment for the frequency of
      readmissions. A model without this adjustment, as opposed to a model with the
      adjustment, produced substantially different HSMR outcomes. The uncertainty
      introduced by these differences exceeded the uncertainty indicated by the 95%
      confidence intervals. Therefore an adjustment for the frequency of readmissions
      should be considered in The Netherlands, since such a model showed more
      favourable quality metric characteristics compared to a model without such an
      adjustment. Other countries could well benefit from a similar adjustment to their
      models. A review period of the data collected over the last three years, at
      least, is advisable.

PMID- 22475459
TI  - Neglected tropical diseases and mental health: a perspective on comorbidity.
AB  - Mental health conditions will be the largest contributor to the global health
      burden by 2030. Our review suggests that neglected tropical diseases (NTDs)
      predispose individuals to poor mental health. Factors predisposing to poor mental
      health include stigma and discrimination, exclusion from participating fully in
      society, reduced access to health and social services, lack of educational
      opportunities, exclusion from income-generation and employment opportunities, and
      restrictions in exercising civil and political rights. These characteristics are
      all features of NTDs, but the mental health of these sufferers has been ignored.
      This review raises an issue of concern and highlights the opportunities for
      research by psychiatrists and psychologists on NTDs.

PMID- 22475460
TI  - Methodologies for the isolation of alternative binders with improved clinical
      potentiality over conventional antibodies.
AB  - The availability of binders to different functional domains of the same protein
      or to physiologically co-operating proteins allows for the simultaneous
      inhibition of independent downstream signaling pathways. This multi-target
      approach represents a promising therapeutic strategy, as demonstrated in the case
      of the synergistic effect of anti-Her2 treatment based on the combined use of the
      trastuzumab and pertuzumab monoclonal antibodies that induce cellular
      cytotoxicity and impair the receptor dimerization, respectively. Therefore, a
      reliable selection method for the recovery of epitope-specific antibodies is
      highly needed. Animal immunization with short peptides resembling the epitope
      sequence for raising conventional antibodies represents an alternative. Panning
      phage displayed libraries of recombinant antibodies such as scFvs and nanobodies
      or of other peptide collections is another option. Although recombinant
      antibodies can provide the same specificity as conventional antibodies, they
      offer at least two further advantages: i) the protocols for the selection of
      epitope-specific antibodies can be rationally designed, and ii) their expression
      as multivalent, bispecific and biparatopic molecules is feasible. This review
      will analyze the recent literature concerning technical aspects related to the
      isolation, the expression as multivalent molecules, and the therapeutic
      applications of binders able to interfere with antigen functional domains. The
      term binder will be preferred when possible to include those molecules, such as
      peptides or affibodies, with at least some proven practical uses.

PMID- 22475462
TI  - [Infliximab-induced psoriasis in an adolescent with ulcerative colitis].

PMID- 22475463
TI  - Rehabilitation of the maxillary arch with implant-supported fixed restorations
      guided by the most apical buccal bone level in the esthetic zone: a clinical
      report.
AB  - This article describes a prosthetically-driven protocol for the rehabilitation of
      the completely edentulous maxillary arch using immediate implant placement and
      loading techniques. After the incisal edges of the planned maxillary central
      incisors are determined, the most apical buccal bone level in the esthetic zone
      serves to guide complete arch rehabilitation.

PMID- 22475461
TI  - Astrocytes conspire with neurons during progression of neurological disease.
AB  - As astrocytes are becoming recognized as important mediators of normal brain
      function, studies into their roles in neurological disease have gained
      significance. Across mouse models for neurodevelopmental and neurodegenerative
      diseases, astrocytes are considered key regulators of disease progression. In
      Rett syndrome and Parkinson's disease, astrocytes can even initiate certain
      disease phenotypes. Numerous potential mechanisms have been offered to explain
      these results, but research into the functions of astrocytes in disease is just
      beginning. Crucially, in vivo verification of in vitro data is still necessary,
      as well as a deeper understanding of the complex and relatively unexplored
      interactions between astrocytes, oligodendrocytes, microglia, and neurons.

PMID- 22475464
TI  - A technique for immediate occlusal implant loading of a completely edentulous
      mandible: a clinical report.
AB  - The protocols described are designed for immediate implant loading of the
      completely edentulous mandible and to provide the patient with a prosthesis that
      incorporates structural durability and esthetics in a time efficient manner.
      Incorporating appropriate diagnostic and surgical procedures, this clinical
      report describes the use of custom-fabricated transparent devices that help the
      clinician identify implant position, thereby reducing the procedural time and
      improving the structural durability and esthetics of the immediate prosthesis.

PMID- 22475465
TI  - Effect of different prosthetic materials on radiation dose distribution in an
      orbital defect: a clinical report.
AB  - It is challenging to treat and irradiate empty cavities with external-beam
      radiation therapy (EBRT) because body contour irregularities can result in dose
      heterogeneities. The use of compensator materials to fill the empty cavities can
      provide a more homogeneous radiation dose distribution. The purposes of this
      clinical report are to describe the use of 3 different materials (elastomeric
      material, water-filled balloon, and acrylic resin) in an orbital defect and
      compare the dosimetric parameters and photon-electron dose distribution during
      EBRT.

PMID- 22475466
TI  - Passivity of fit of CAD/CAM and copy-milled frameworks, veneered frameworks, and
      anatomically contoured, zirconia ceramic, implant-supported fixed prostheses.
AB  - STATEMENT OF PROBLEM: There is less information on the quality of fit of zirconia
      frameworks with or without ceramic veneer than on anatomically contoured milled
      zirconia restorations. PURPOSE: The purpose of this in vitro study was to
      evaluate the strain development of CAD/CAM fabricated zirconia ceramic frameworks
      with and without ceramic veneering, copy-milled zirconia ceramic frameworks, and
      copy-milled zirconia ceramic anatomic contour restorations. MATERIAL AND METHODS:
      Four groups of 3-unit implant-supported cement-retained restorations were
      fabricated (n=10) to fit an in vitro model with 2 implants. Strain gauges which
      recorded the strain development of all restorations during cementation were
      attached to the model mesially and distally adjacent to the implants. Mean
      absolute strain values were recorded for statistical analysis (MANOVA with
      Pillai's trace; alpha=.05). RESULTS: Mean absolute strain development at the
      different strain gauge locations ranged from 83.23 um/m for copy-milled zirconia
      ceramic anatomic contour restorations to 301.20 um/m for veneered CAD/CAM
      fabricated zirconia ceramic restorations. Significant effects (P<.001) of the
      fixed factors restoration type and veneering status, as well as of their
      interaction term (P=.001) were found. Ceramic veneering of CAD/CAM frameworks
      resulted in higher strain development, whereas the greater volume in copy-milled
      anatomic contour restorations did not affect accuracy. CONCLUSIONS: With the
      systems used in this study, zirconia ceramic-based anatomic contour restorations
      show greater passivity of fit than ceramic veneered CAD/CAM fabricated zirconia
      ceramic frameworks.

PMID- 22475467
TI  - Microleakage of endodontically treated teeth restored with 3 different adhesive
      systems and 4 different fiber-reinforced posts.
AB  - STATEMENT OF PROBLEM: Despite recent advances in adhesive dentistry, fiber
      reinforced post/resin cement/dentin adhesive combinations are not able to prevent
      microleakage. While studies have examined microleakage in endodontically treated
      teeth restored with posts and cores, microleakage among post and adhesive systems
      remains a concern. PURPOSE: This study compared the sealing properties of 4
      adhesively luted post systems: glass fiber, quartz-glass fiber, zirconia-glass
      fiber and polyethylene fiber posts. MATERIAL AND METHODS: Forty-eight permanent
      maxillary central incisors were divided into 4 groups (n=12). Post space was
      prepared and each post was adhesively luted with 1 of 3 systems: a 1-stage self
      etch, a 2-stage total-etch, and a 3-stage total-etch adhesive. The specimens were
      separately immersed in freshly prepared 2% methylene blue solution for 1 week.
      The cleaned specimens were then embedded in autopolymerizing acrylic resin. The
      teeth were horizontally sectioned into apical, middle, and coronal portions. An
      occlusal view of each section was digitally photographed with a stereomicroscope.
      The methylene blue-infiltrated surface for each specimen was measured and data
      were collected with software. Dye penetration was estimated as the ratio of the
      methylene blue-infiltrated surface to the total dentin surface. Nonparametric
      data were analyzed with the Kruskal-Wallis test (alpha=.05). The Mann-Whitney U
      test was used to compute multiple pairwise comparisons that identified
      differences among groups. Dentin-luting agent and post interfaces were evaluated
      with a scanning electron microscope. RESULTS: Significant differences in adhesive
      and post systems were observed in all sectioned regions (P<.05). There were
      significant differences between the apical and coronal sections of each post
      type, and between the following pairs: middle versus coronal sections of zirconia
      glass fiber and glass fiber posts and apical versus middle sections of quartz
      glass fiber and polyethylene fiber posts (P<.05). No significant differences were
      found among post types. The variables of middle section and 3-stage adhesive
      produced significant differences in microleakage between the following post
      pairs: zirconia-glass fiber versus quartz-glass fiber, zirconia-glass fiber
      versus polyethylene fiber, and quartz-glass fiber versus polyethylene fiber
      (P<.05). CONCLUSIONS: The 3-stage adhesive and zirconia-glass fiber posts
      demonstrated the least microleakage.

PMID- 22475468
TI  - The effects of desensitizing resin, resin sealing, and provisional cement on the
      bond strength of dentin luted with self-adhesive and conventional resincements.
AB  - STATEMENT OF PROBLEM: Self-adhesive resin cements were designed to bond without
      any pretreatment of dentin. However, pretreatments such as the application of
      desensitizing resin or the resin sealing of dentin with priming/bonding solutions
      might influence the bonding quality of these self-adhesive resin cements. Little
      is known about the effect of dentin pretreatment on the bond quality of self
      adhesive resin cements. PURPOSE: This study evaluated whether dentin
      desensitizing or sealing methods influenced the shear bond strength of 1 self
      adhesive and 2 conventional resin cements. MATERIAL AND METHODS: One-hundred and
      eighty human molars were assigned to 5 different pretreatment groups: 1) freshly
      ground dentin, 2) glutaraldehyde/hydroxyethylmethacrylate (HEMA) desensitized
      dentin (Gluma), 3) contamination of desensitized dentin with provisional cement,
      4) sealed dentin (dual bonding technique), and 5) contamination of sealed dentin
      with provisional cement. The shear bond strength of a self-adhesive resin cement
      (RelyX Unicem; RXU) and 2 conventional resin cements (Variolink II; VAR, Panavia
      21; PAN) was assessed for each pretreatment group (n=12 per cement types). Two
      way ANOVA and 1-way ANOVA together with the post hoc Tukey multiple comparison
      (alpha=.05) were performed. RESULTS: On freshly ground dentin, PAN exhibited the
      highest shear bond strength values (P<.001). The use of the glutaraldehyde/HEMA
      resulted in a significant increase in the bond strength of RXU as compared to
      fresh dentin (P<.001). Resin sealing of dentin increased the bond strength of RXU
      but had no significant effect on VAR or PAN. RXU exhibited the highest mean bond
      strength after the contamination of resin-sealed dentin by provisional cement.
      CONCLUSIONS: Glutaraldehyde/HEMA treatment and resin sealing of dentin have a
      beneficial effect on the shear bond strength of self-adhesive resin cement (RXU).
      Contamination of dentin with provisional cement has no influence on the bond
      strength of the self-adhesive resin cement (RXU) or VAR but lowered the bond
      strength of PAN.

PMID- 22475469
TI  - Classification of maxillectomy defects: a systematic review and criteria
      necessary for a universal description.
AB  - STATEMENT OF PROBLEM: Maxillectomy defects are complex and involve a number of
      anatomic structures. Several maxillectomy defect classifications have been
      proposed with no universal acceptance among surgeons and prosthodontists.
      Established criteria for describing the maxillectomy defect are lacking. PURPOSE:
      This systematic review aimed to evaluate classification systems in the available
      literature, to provide a critical appraisal, and to identify the criteria
      necessary for a universal description of maxillectomy and midfacial defects.
      MATERIAL AND METHODS: An electronic search of the English language literature
      between the periods of 1974 and June 2011 was performed by using PubMed, Scopus,
      and Cochrane databases with predetermined inclusion criteria. Key terms included
      in the search were maxillectomy classification, maxillary resection
      classification, maxillary removal classification, maxillary reconstruction
      classification, midfacial defect classification, and midfacial reconstruction
      classification. This was supplemented by a manual search of selected journals.
      After application of predetermined exclusion criteria, the final list of articles
      was reviewed in-depth to provide a critical appraisal and identify criteria for a
      universal description of a maxillectomy defect. RESULTS: The electronic database
      search yielded 261 titles. Systematic application of inclusion and exclusion
      criteria resulted in identification of 14 maxillectomy and midfacial defect
      classification systems. From these articles, 6 different criteria were identified
      as necessary for a universal description of a maxillectomy defect. Multiple
      deficiencies were noted in each classification system. Though most articles
      described the superior-inferior extent of the defect, only a small number of
      articles described the anterior-posterior and medial-lateral extent of the
      defect. Few articles listed dental status and soft palate involvement when
      describing maxillectomy defects. CONCLUSIONS: No classification system has
      accurately described the maxillectomy defect, based on criteria that satisfy both
      surgical and prosthodontic needs. The 6 criteria identified in this systematic
      review for a universal description of a maxillectomy defect are: 1) dental
      status; 2) oroantral/nasal communication status; 3) soft palate and other
      contiguous structure involvement; 4) superior-inferior extent; 5) anterior
      posterior extent; and 6) medial-lateral extent of the defect. A criteria-based
      description appears more objective and amenable for universal use than a
      classification-based description.

PMID- 22475470
TI  - Enhancing the online presence of a dental practice.
AB  - This article describes methods for enhancing the online presence of a dental
      practice to gain market share and facilitate communication with current and
      prospective patients. Topics discussed include creation of a website that will
      help patients easily locate the practice. The importance of back links and
      embedded keywords is stressed. A method for identifying competitors' online
      marketing strategies also is presented, along with discussions of patient reviews
      and pay-per-click advertising options.

PMID- 22475471
TI  - One-step mounting of diagnostic casts demonstrating loss of posterior occlusal
      support.

PMID- 22475472
TI  - Mood-congruent and mood-incongruent psychotic symptoms in major depression: the
      role of severity and personality.
AB  - BACKGROUND: Whether psychotic symptoms in major depression (MD) are better
      explained by a "severity model" or by a "vulnerability model", with personality
      as a predisposing factor, is still debated. The aim of the present study was to
      evaluate in MD the relationship between the content of psychotic features (mood
      congruent (MC) or mood incongruent (MI)) and severity of depression or
      personality traits. METHODS: 62 inpatients affected by MD with psychotic features
      were divided into three groups on the basis of the content of psychotic symptoms:
      MC, MI, mixed MC-MI. All subjects completed the SCID-IV, the Structured Clinical
      Interview for DSM-IV Personality Disorders and the Hamilton Rating Scale for
      Depression. Personality was assessed after MD remission. RESULTS: MI psychotic
      symptoms were positively associated with schizotypal traits, whereas MC symptoms
      were positively related to obsessive-compulsive traits and severity of
      depression. Patients with both MC and MI psychotic symptoms were characterized by
      a personality profile and depression severity standing in a middle position
      between the MC and MI groups. LIMITATIONS: The main limitations of the study are
      represented by the small sample size, the time of assessment of personality and
      the inclusion of only unipolar depression. CONCLUSIONS: Our findings suggest that
      both depression severity and personality profile, independently from each other,
      model the content of psychotic symptoms, confirming the validity of subgrouping
      psychotic depression into two distinct MC and MI types and supporting the
      inclusion of a third mixed MC-MI type because of its intermediate position in
      personality profile and severity between the MC or MI group.

PMID- 22475473
TI  - Suicidal ideation and temperament: an investigation among college students.
AB  - BACKGROUND: Suicide is a major health problem accounting for up to 1.5 percent of
      all deaths worldwide and represents one of the most common causes of death in
      adolescents and young adults. A number of studies has been performed to establish
      risk factors for suicide in patients with psychiatric disorders including
      temperamental features. This study set out to assess the relationship between
      suicidal ideation and temperament in young adults. METHODS: A cross-sectional
      sample of healthy college students (n=1381) was examined using a self-rating
      questionnaire. Suicidal ideation, social background, educational status,
      substance abuse, and affective temperament according to TEMPS-M were assessed.
      Predictors of lifetime suicidal ideation were examined in multivariate logistic
      regression analyses. RESULTS: Suicidal ideation was reported by 12.5% of all
      subjects at some point in their life and was higher in nicotine dependents, youth
      with alcohol related problems and users of illicit substances as well as in youth
      with lower educational status. Lifetime suicidal ideation was associated with the
      anxious, depressive and cyclothymic temperament in both sexes and the irritable
      temperament in males. These results remained significant after adjustment for
      smoking status, frequency of alcohol consumption, drug experience and educational
      status in a multivariate logistic regression analysis. LIMITATIONS: The use of
      self-rating instruments always reduces objectivity and introduces the possibility
      of misreporting. CONCLUSIONS: Considering the fact that many subjects completing
      suicide have never been diagnosed with mental disorders it might be reasonable to
      include an investigation of temperament in screenings for risk of suicide. This
      might be especially useful for health care professionals without mental health
      care background.

PMID- 22475474
TI  - The association of affective temperaments with impairment and psychopathology in
      a young adult sample.
AB  - BACKGROUND: Previous research has examined the association of affective
      temperaments, as measured by the TEMPS-A, with DSM bipolar disorders. However,
      the relation of the TEMPS-A with risk for bipolar disorder remains unclear. The
      present study examined the association of affective temperaments with
      psychopathology, personality, and functioning in a nonclinically ascertained
      sample of young adults at risk for bipolar disorder. METHODS: One hundred forty
      five participants completed the TEMPS-A, as well as interview and questionnaire
      measures of psychopathology, personality, and functioning. RESULTS:
      Cyclothymic/irritable temperament was associated with a range of deleterious
      outcomes, including mood disorders and impaired functioning. It was negatively
      associated with agreeableness and conscientiousness, and positively associated
      with current depressive symptoms, neuroticism, borderline symptoms, impulsivity,
      and grandiosity. Dysthymic temperament was positively associated with current
      depressive symptoms, neuroticism and agreeableness, but was unrelated to mood
      psychopathology. Hyperthymic temperament was associated with bipolar spectrum
      disorders, hypomania or interview-rated hyperthymia, extraversion, openness,
      impulsivity, and grandiosity. LIMITATIONS: The present study was cross-sectional.
      Longitudinal studies utilizing the TEMPS-A are needed to better understand the
      predictive validity of the TEMPS-A for the development of bipolar disorder.
      CONCLUSIONS: Early identification of individuals who fall on the bipolar spectrum
      may hasten appropriate intervention or monitoring, and prevent misdiagnosis. The
      TEMPS-A appears to be a useful tool for assessing affective temperaments and
      bipolar spectrum psychopathology. The results support previous research
      documenting the association of cyclothymic/irritable temperament with bipolar
      psychopathology and other negative outcomes.

PMID- 22475475
TI  - Weight change before and after the introduction of solids: results from a
      longitudinal birth cohort.
AB  - We studied the association, and its direction, between the introduction of solids
      and weight-for-height (WFH) change between birth and 45 months. Pregnant women
      were asked to participate in a birth cohort during their first antenatal visit.
      Data from 3184 children were used. The timing of the introduction of solids was
      reported by the mother from a questionnaire at 12 months postpartum, and
      categorised into very early (0-3 months), early (3-6 months) and timely (after 6
      months) introduction of solids. Anthropometric data were collected during
      standardised child health centre visits. WFH was converted into a z-score.
      Repeated-measurements analyses with splines positioned according to the moments
      of solid introduction were used to obtain estimates for WFH change before and
      after the introduction of solids. Analyses were adjusted for educational level,
      ethnicity, smoking during pregnancy, mother's BMI, breast-feeding, history of
      food allergy and infant's hospital admission. Before solids were introduced,
      weight gain was higher in children introduced to solids early (z= 0.65, 95 % CI
      0.34, 0.95) than in children introduced to solids very early (z= 0.02, 95 % CI 
      0.03, 0.08) and timely (z= -0.04, 95 % CI -0.05, -0.03). Shortly after the
      introduction of solids, children introduced to solids very early and early showed
      a relative decrease in WFH. WFH change did not differ between the solid
      introduction groups after 12 months, and at that time, weight change was as
      expected (i.e. z= 0). We therefore conclude that differences in WFH in childhood
      are not the result of early introduction to solids.

PMID- 22475476
TI  - Personality modulation of (un)conscious processing: Novelty Seeking and
      performance following supraliminal and subliminal reward cues.
AB  - This study provides evidence that personality traits associated with
      responsiveness to conscious reward cues also influence responsiveness to
      unconscious reward cues. Participants with low and high levels of Novelty Seeking
      (NS) performed updating tasks in which they could either gain 1 euro or 5 cents.
      Gains were presented either supraliminally or subliminally at the beginning of
      each trial. Results showed that low NS participants performed better in the high
      reward than in the low-reward condition, whereas high NS participants'
      performance did not differ between reward conditions. Interestingly, we found
      that low NS participants performed significantly better when rewards were
      presented unconsciously, whereas high NS participants' performance did not differ
      whether reward cues were presented subliminally or supraliminally. Our findings
      highlight the necessity of taking personality into account in unconscious
      cognition research. They also suggest that individual differences might determine
      whether implicit and explicit motives have similar or complementary influences.

PMID- 22475477
TI  - Concepts about agency constrain beliefs about visual experience.
AB  - Recent research exploring phenomena such as change blindness, inattentional
      blindness, attentional blink and repetition blindness has revealed a number of
      counterintuitive ways in which apparently salient visual stimuli often go
      unnoticed. In fact, large majorities of subjects sometimes predict that they
      would detect visual changes that actually are rarely noticed, suggesting that
      people have strong beliefs about visual experience that are demonstrably
      incorrect. However, for other kinds of visual metacognition, such as picture
      memory, people underpredict performance. This paper describes two experiments
      demonstrating that both these overpredictions of change detection, and
      underpredictions of visual memory can be linked with intuitions about the visual
      experience of different kinds of agents. Subjects predicted more visual change
      detection and poorer visual memory for mechanical representational systems (e.g.
      computer programs) when these were anthropomorphized using intentional
      terminology.

PMID- 22475478
TI  - [Mohs micrographic surgery: why? Why not?].

PMID- 22475479
TI  - [Interest and reliability of frozen section biopsy in the treatment of skin
      tumors].
AB  - INTRODUCTION: Association of surgical treatment combined to frozen section
      biopsies appears to be one of the most appropriate therapeutic solution for the
      treatment of skin carcinomas. We report our experience on 269 tumors assessed
      with frozen sections. Our goal was to first study the benefit of a one-time
      surgical approach, then to better target the tumors eligible for this examination
      and finally to number the difference between frozen section and final histology
      studies. MATERIALS AND METHODS: This is a retrospective analysis of 269 tumors,
      operated on an outpatient basis with frozen section followed later by a final
      histology study. All being performed by the same team of surgeons and
      pathologist. Only previously biopsied and diagnosed basal cell or squamous cell
      tumors were included. The recorded data were: location of tumor; histological
      type; involved margins; number of cuts; differences between frozen section and
      final histological studies, which conduct to a two-time surgical approach; number
      of tumors for which frozen section was impossible during surgery and that lead to
      a two-time surgical approach; type of reconstruction; number of recurrence.
      RESULTS: The follow up was 48 months (26.6 to 78.1). Histogical analyses were
      carried on basal cell carcinoma (92%), squamous cell carcinoma (8%) with a
      topographic distribution mainly in face and neck (72%). Of the 269 tumors
      excised, 207 representing 77% had a sufficient safety margin, 62 representing 23%
      had at least one invaded bank that required further surgical resection. We found
      seven cases of two-time surgical approach. In three cases, it was secondary to
      medical decision because of a technical difficulty of histologists. In one case,
      histological diagnosis can't be obtained by frozen section study. In three cases,
      we found a difference between frozen section and final study. CONCLUSION: The
      benefit provided by the frozen section takes its value in the treatment of face
      and neck tumors, whose optimal margins are sometimes difficult to obtain and
      minimal scar ransom necessary. A one-time surgery was made possible to us thanks
      to this fast examination. The low rate of second surgery and recurrence allows us
      to demonstrate the reliability of this technique.

PMID- 22475480
TI  - [Diagnosis and treatment management of basal cell skin carcinoma - guidelines
      analysis].
AB  - Basal cell carcinoma (BCC) is the most frequent skin cancer in France. BCC has
      above all a local evolution with an important locoregional morbidity. BCC are
      found in 80% in the cervicofacial region. Surgery is currently recognized to be
      the most reliable treatment. The surgeon needs to achieve an in sano excision and
      must recover the defect with the less aesthetic consequences. The aim of this
      work is to combine and to get-at-able the recommandations of the "Haute Autorite
      de sante" of 2004, and also to supply some details for the clinical practice of
      the plastic surgeon.

PMID- 22475481
TI  - Juxtaposition of heterochromatic and euchromatic regions by chromosomal
      translocation mediates a heterochromatic long-range position effect associated
      with a severe neurological phenotype.
AB  - BACKGROUND: The term "position effect" is used when the expression of a gene is
      deleteriously affected by an alteration in its chromosomal environment even
      though the integrity of the protein coding sequences is maintained. We describe a
      patient affected by epilepsy and severe neurodevelopment delay carrying a
      balanced translocation t(15;16)(p11.2;q12.1)dn that we assume caused a position
      effect as a result of the accidental juxtaposition of heterochromatin in the
      euchromatic region. RESULTS: FISH mapped the translocation breakpoints (bkps) to
      15p11.2 within satellite III and the 16q12.1 euchromatic band within the ITFG1
      gene. The expression of the genes located on both sides of the translocation were
      tested by means of real-time PCR and three, all located on der(16), were found to
      be variously perturbed: the euchromatic gene NETO2/BTCL2 was silenced, whereas
      VPS35 and SHCBP1, located within the major heterochromatic block of chromosome
      16q11.2, were over-expressed. Pyrosequencing and chromatin immunoprecipitation of
      NETO2/BTCL2 and VPS35 confirmed the expression findings. Interphase FISH analysis
      showed that der(16) localised to regions occupied by the beta satellite
      heterochromatic blocks more frequently than der(15). CONCLUSIONS: To the best of
      our knowledge, this is the first report of a heterochromatic position effect in
      humans caused by the juxtaposition of euchromatin/heterochromatin as a result of
      chromosomal rearrangement. The overall results are fully in keeping with the
      observations in Drosophila and suggest the occurrence of a human heterochromatin
      position effect associated with the nuclear repositioning of the der(16) and its
      causative role in the patient's syndromic phenotype.

PMID- 22475482
TI  - Human peroxiredoxin 1 modulates TGF-beta1-induced epithelial-mesenchymal
      transition through its peroxidase activity.
AB  - The epithelial-to-mesenchymal transition (EMT), which is induced by transforming
      growth factor-beta1 (TGF-beta1), is an important event that allows cancer cells
      to obtain invasive and metastatic characteristics. Although human peroxiredoxin 1
      (hPrx1) has been implicated in tumor progression (e.g., invasion and metastasis),
      little is known about the role of hPrx1 in the EMT process during tumorigenesis.
      Here, we investigated the regulatory effect of hPrx1 during TGF-beta1-induced EMT
      in A549 lung adenocarcinoma cells. We observed that high hPrx1 levels
      downregulated E-cadherin expression, and low hPrx1 levels upregulated E-cadherin
      expression, suggesting that the hPrx1 level may be correlated with EMT. Knockdown
      of hPrx1 significantly inhibited TGF-beta1-induced EMT and cell migration,
      whereas hPrx1 overexpression enhanced TGF-beta1-induced EMT and cell migration.
      In contrast to wild-type hPrx1, a peroxidase-inactive hPrx1 mutant (hPrx1-C51S)
      resulted in markedly increased E-cadherin expression. Moreover, hPrx1 regulated
      the expression of two E-cadherin transcriptional repressors, Snail and Slug.
      These findings provide new insight into the role of hPrx1 in regulating TGF-beta1
      induced EMT.

PMID- 22475483
TI  - Dicer has a crucial role in the early stage of adipocyte differentiation, but not
      in lipid synthesis, in 3T3-L1 cells.
AB  - Dicer is a rate-limiting enzyme for microRNA (miRNA) synthesis. To determine the
      effects of Dicer on adipogenesis, we performed stage-specific knockdown of Dicer
      using adenovirus encoding short-hairpin RNAi against Dicer in 3T3-L1 cells. When
      cells were infected with the adenovirus before induction of adipocyte
      differentiation, Dicer RNAi suppressed the gene expression of inducers of
      adipocyte differentiation such as PPARgamma, C/EBPalpha, and FAS in 3T3-L1 cells
      during adipocyte differentiation. Concurrently, both adipocyte differentiation
      and cellular lipid accumulation were cancelled by Dicer RNAi when compared with
      control RNAi. Meanwhile, we addressed the roles of Dicer in lipid synthesis and
      accumulation in the final stages of differentiation. When the differentiated
      cells at day 4 after induction of differentiation were infected with adenovirus
      Dicer RNAi, cellular lipid accumulation was unchanged. Consistent with this,
      Dicer RNAi had no effects on the expression of genes related to cellular lipid
      accumulation, including PPARgamma and FAS. Thus, Dicer controls proadipogenic
      genes such as C/EBPalpha and PPARgamma in the early, but not in the late, stage
      of adipogenesis via regulation of miRNA synthesis.

PMID- 22475484
TI  - ATF3 inhibits adipocyte differentiation of 3T3-L1 cells.
AB  - ATF3 is a stress-adaptive gene that regulates proliferation or apoptosis under
      stress conditions. However, the role of ATF3 is unknown in adipocyte cells.
      Therefore, in this study, we investigated the functional role of ATF3 in
      adipocytes. Both lentivirus-mediated overexpression of ATF3 and stably
      overexpressed ATF3 inhibited adipocyte differentiation in 3T3-L1 cells, as
      revealed by decreased lipid staining with oil red staining and reduction in
      adipogenic genes. Thapsigargin treatment and overexpression of ATF3 decreased
      C/EBPalpha transcript and repressed the activity of the 3.6-kb mouse C/EBPalpha
      promoter, demonstrating that ATF3 downregulates C/EBPalpha expression.
      Transfection studies using mutant constructs containing 5'-deletions in the
      C/EBPalpha promoter revealed that a putative ATF/CRE element, GGATGTCA, is
      located between -1921 and -1914. Electrophoretic mobility shift assay and
      chromatin immunoprecipitation assay demonstrated that ATF3 directly binds to
      mouse C/EBPalpha promoter spanning from -1928 to -1907. Both chemical hypoxia
      mimetics or physical hypoxia led to reduce the C/EBPalpha mRNA and repress the
      promoter activity of the C/EBPalpha gene, whereas increase ATF3 mRNA, suggesting
      that ATF3 may contribute to the inhibition of adipocyte differentiation in
      hypoxia through downregulation of C/EBPalpha expression. Collectively, these
      results demonstrate that ATF3 represses the C/EBPalpha gene, resulting in
      inhibition of adipocyte differentiation, and thus plays a role in hypoxia
      mediated inhibition of adipocyte differentiation.

PMID- 22475485
TI  - Designation of enzyme activity of glycine-N-acyltransferase family genes and
      depression of glycine-N-acyltransferase in human hepatocellular carcinoma.
AB  - The human glycine-N-acyltransferase (hGLYAT) gene and two related-genes (GLYATL1
      and GLYATL2) were isolated. Human GLYAT, GLYATL1, and GLYATL2 cDNAs were isolated
      and shown to encode polypeptides of 295, 302, and 294 amino acids, respectively.
      GLYAT catalyzes glycine-N-acyltransfer reaction with benzoyl-CoA acting as a
      typical aralkyl transferase, while GLYATL1 catalyzed glutamine-N-acyltransfer
      reaction with phenylacetyl-CoA as an arylacetyl transferase. GLYAT was shown to
      be expressed specifically in the liver and kidney, and the cellular localization
      of GLYAT protein was restricted to the mitochondria. Interestingly, labeling
      using highly affinity purified anti-GLYAT antibody revealed that GLYAT expression
      was suppressed in all hepatocellular carcinomas, but not in other liver diseases.
      hGLYAT repression in cancerous cells in the liver was controlled at the
      transcriptional level. hGLYAT is a good candidate as a novel marker of
      hepatocellular carcinoma and may be a key molecule in the transition between
      differentiation and carcinogenesis of liver cells.

PMID- 22475486
TI  - Detection of asymmetric distribution of phospholipids by fluorescence resonance
      energy transfer.
AB  - It is well established that the plasma membrane exhibits an asymmetric
      distribution of lipids between the inner and outer leaflets of the lipid bilayer.
      Recent studies suggest that the asymmetric distribution changes locally and
      temporarily, accompanied by cellular events. However, available methods to detect
      lipid asymmetry lack spatio-temporal resolution. As a technique of potential use
      for real-time imaging of lipid asymmetry, we a novel method that utilizes
      fluorescence resonance energy transfer (FRET) between NBD-labeled phospholipids
      (donor) and extracellular rhodamine (acceptor). When cell apoptosis was induced
      by staurosporine, the fluorescence intensity of NBD-labeled phosphatidylserine
      decreased owing to FRET from NBD to rhodamine. This method provides a simple way
      to detect lipid asymmetry and may be useful for observing dynamic changes in
      asymmetric distribution of lipids.

PMID- 22475487
TI  - Hypoxia-inducible factor 1 regulated ARC expression mediated hypoxia induced
      inactivation of the intrinsic death pathway in p53 deficient human colon cancer
      cells.
AB  - Apoptosis repressor with caspase recruitment domain (ARC), an anti-apoptotic
      protein, plays an important role in the regulation of apoptosis by blocking both
      the extrinsic and intrinsic death pathways. However, its regulatory mechanism
      remains largely undefined. Here, we reported that hypoxia up-regulated the
      expression of ARC in p53 deficient human colon cancer cells. Moreover, ARC is a
      direct target of the hypoxia-inducible factor 1 (HIF-1), a key transcriptional
      factor for the cellular response to hypoxia. Silencing the expression of HIF
      1alpha in SW480 colon cancer cells by RNA interference abolished hypoxia induced
      ARC expression. Using luciferase reporter and ChIP assay, we showed that HIF
      1alpha directly bound to hypoxia-responsive element located at -419 to -414 of
      ARC gene, which is essential for HIF-1-induced expression. As a result of the
      increased ARC expression, TRAIL-induced apoptosis was reduced by hypoxia. These
      discoveries would shed novel insights on the mechanisms for ARC expression
      regulation and hypoxia induced inactivation of the intrinsic death pathway.

PMID- 22475488
TI  - Heteroplasmy levels of mtDNA1555A>G mutation is positively associated with
      diverse phenotypes and mutation transmission in a Chinese family.
AB  - The mtDNA 1555A>G mutation was considered to be one of the most common causes of
      aminoglycoside-induced and non-syndromic hearing loss. However, this mutation was
      always found in homoplasmy with high phenotypic heterogeneity. Recently this
      mutation in heteroplasmy has been reported in several studies. In the present
      study, we have collected a large Chinese family harboring heteroplasmic mtDNA
      1555A>G mutation with diverse clinical phenotypes. To investigate the
      relationship between the mutation load and the severity of hearing loss under
      Eastern Asian background, we performed clinical, molecular, genetic and
      phylogenic analysis. This pedigree was characterized by coexistence of eight
      subjects with homoplasmic mutation and ten subjects with various degrees of
      heteroplasmy, and the results suggested that there was a strong correlation
      between the mutation load and the severity/age-onset of hearing loss (r=0.758,
      p<0.001). We noticed that the mutation level of offspring was associated with
      their mothers' in this pedigree, which indicated that maybe exist a regular
      pattern during the process of the heteroplasmic transmission. In addition,
      analysis of the complete mtDNA genome of this family revealed that it belonged to
      Eastern Asian haplogroup B4C1. In addition, a rare homoplasmic mtDNA 9128T>C
      variant was identified, it located at a strictly conserved site of mtDNA ATP6
      gene.

PMID- 22475489
TI  - Identification of distinct physiochemical properties of toxic prefibrillar
      species formed by Abeta peptide variants.
AB  - The formation of amyloid-beta peptide (Abeta) aggregates at an early stage during
      the self-assembly process is an important factor in the development of
      Alzheimer's disease. The toxic effect is believed to be exerted by prefibrillar
      species of Abeta. It is therefore important to identify which prefibrillar
      species are toxic and characterize their distinct properties. In the present
      study, we investigated the in vitro aggregation behavior of Abeta-derived
      peptides possessing different levels of neurotoxic activity, using fluorescence
      spectroscopy in combination with transmission electron microscopy. The toxicity
      of various Abeta aggregates was assessed by using cultures of human neuroblastoma
      cells. Through combined use of the fluorescence probe 8-anilino-1
      napthalenesulfonate (ANS) and the novel luminescent probe pentamer formyl
      thiophene acetic acid (p-FTAA), we were able to identify those Abeta peptide
      derived prefibrillar species which exhibited cellular toxicity. In particular,
      species, which formed early during the aggregation process and showed strong p
      FTAA and ANS fluorescence, were the species that possessed toxic activities.
      Moreover, by manipulating the aggregation conditions, it was possible to change
      the capacity of the Abeta peptide to form nontoxic versus toxic species.

PMID- 22475490
TI  - [Irregular antibody testing during pregnancy in Tunisia: clinical study of 5369
      women].
AB  - PURPOSE OF THE STUDY: To evaluate the prevalence of alloimmunization in women
      followed in an obstetrical environment in Tunisia, to identify the specificities
      of antibodies found and to determine factors that could influence the appearance
      of this immunization. METHODS: We proceeded to a retrospective analysis of search
      for irregular antibodies in women followed up in obstetrical environment over
      nine consecutive years (2000-2008). The panel was officially defined and produced
      by the Regional Centre for Blood Transfusion in Sfax (Tunisia). RESULTS: Overall
      5369 women benefited from 6575 antibody testing (average: 1.22; extremes: 1-14).
      The results were positive for 278 women (5.17 %), allowing to identify 216
      antibodies or associations of antibodies. Among identified antibodies, those
      immune were found in 198 women. The rate of alloimmunization was 3.68 %
      (198/5369). The majority of the antibodies found was anti-Rh1, isolated or
      associated with another antibody, in 84.3 % of the total immunized women. The
      immunization of women according to the number of gestations showed a significant
      increasing rate ranging from 2.34 % for a first gestation to 5.27 % for four
      gestations or more. In addition, a significant difference was also noted between
      the rate of immunization in women who had received anti-Rh1 immunoglobulin and
      those who had not. CONCLUSION: Anti-Rh1 immunization is the most frequent in the
      population of studied women. This could denote of an insufficiency in pregnancies
      follow-up and immunoprophylaxis protocols.

PMID- 22475491
TI  - Balance between clinical and environmental responses to infectious diseases.

PMID- 22475492
TI  - Cervical pessary use and preterm birth: how little we know.

PMID- 22475493
TI  - Cervical pessary in pregnant women with a short cervix (PECEP): an open-label
      randomised controlled trial.
AB  - BACKGROUND: Most previous studies of the use of cervical pessaries were either
      retrospective or case controlled and their results showed that this intervention
      might be a preventive strategy for women at risk of preterm birth; no randomised
      controlled trials have been undertaken. We therefore undertook a randomised,
      controlled trial to investigate whether the insertion of a cervical pessary in
      women with a short cervix identified by use of routine transvaginal scanning at
      20-23 weeks of gestation reduces the rate of early preterm delivery. METHODS: The
      Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in five
      hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of
      25 mm or less were randomly assigned according to a computer-generated allocation
      sequence by use of central telephone in a 1:1 ratio to the cervical pessary or
      expectant management (without a cervical pessary) group. Because of the nature of
      the intervention, this study was not masked. The primary outcome was spontaneous
      delivery before 34 weeks of gestation. Analysis was by intention to treat. This
      study is registered with ClinicalTrials.gov, number NCT00706264. FINDINGS: 385
      pregnant women with a short cervix were assigned to the pessary (n=192) and
      expectant management groups (n=193), and 190 were analysed in each group.
      Spontaneous delivery before 34 weeks of gestation was significantly less frequent
      in the pessary group than in the expectant management group (12 [6%] vs 51 [27%],
      odds ratio 0.18, 95% CI 0.08-0.37; p<0.0001). No serious adverse effects
      associated with the use of a cervical pessary were reported. INTERPRETATION:
      Cervical pessary use could prevent preterm birth in a population of appropriately
      selected at-risk women previously screened for cervical length assessment at the
      midtrimester scan. FUNDING: Instituto Carlos III.

PMID- 22475494
TI  - A comparison of the cost of generic and branded food products in Australian
      supermarkets.
AB  - OBJECTIVE: Food cost is an important factor influencing the consumption of
      nutritious foods and subsequent chronic disease risk. The present study compared
      the cost of branded food products with their generic equivalents across a range
      of food categories. SETTING: The survey was conducted within two major
      supermarket chains across six locations in Sydney, Australia (n 12). DESIGN:
      Price differences were calculated for 'core' (nutrient dense and low in energy)
      and 'extra' (high in undesirable nutrients and/or energy) packaged foods (n 22)
      between generic and branded items. RESULTS: A cost saving of 44 % was found by
      purchasing generic over branded products across all food categories. The most
      significant savings were for core foods, such as bread and cereals, and the
      smallest cost savings were seen for fruit products. There was little variation in
      cost saving between branded and generic products by socio-economic status of the
      supermarket location. CONCLUSIONS: The large price differential between branded
      and generic food products implies that consumers, particularly those on lower
      incomes, could benefit financially from purchasing generic items. The promotion
      of core generic products may be an effective strategy to assist people on lower
      incomes to meet dietary guidelines.

PMID- 22475495
TI  - On the evils of group averaging: commentary on Nevin's "Resistance to extinction
      and behavioral momentum".
AB  - Except under unusually favorable circumstances, one can infer from functions
      obtained by averaging across the subjects neither the form of the function that
      describes the behavior of the individual subject nor the central tendencies of
      descriptive parameter values. We should restore the cumulative record to the
      place of honor as our means of visualizing behavioral change, and we should base
      our conclusions on analyses that measure where the change occurs in these
      response-by-response records of the behavior of individual subjects. When that is
      done, we may find that the extinction of responding to a continuously reinforced
      stimulus is faster than the extinction of responding to a partially reinforced
      stimulus in a within-subject design because the latter is signaled extinction.

PMID- 22475497
TI  - Isolated effects of number of acquisition trials on extinction of rat conditioned
      approach behavior.
AB  - Four conditioned approach experiments with rats assessed for effects of number of
      acquisition trials on extinction of conditioned responding, when number of
      acquisition sessions and total acquisition time were held constant. In Experiment
      1, 32 trials per acquisition session led to more extinction responding than did 1
      or 2 trials per session but less than did 4 trials per session. In Experiment 2,
      2 trials per acquisition session led to more spontaneous recovery than did 32
      trials per session. These latter findings are reminiscent of the overtraining
      extinction effect (OEE). Experiment 3 attempted to reduce the OEE with a
      preconditioning phase of partial reinforcement. Experiment 4 attempted to reduce
      the beneficial within-subject effects of increasing the number of acquisition
      trials on extinction observed by Gottlieb and Rescorla (2010) by extinguishing
      stimuli in different sessions. Overall, results suggest a procedural asymmetry:
      between-subject, increasing the number of trials between any pair of trials does
      not lead to greater persistence of responding during extinction; within-subject,
      it does. Results are discussed from an associative perspective, with a focus on
      explanations involving either frustration or comparator mechanisms, and from an
      information processing perspective, with a focus on Rate Estimation Theory.

PMID- 22475498
TI  - EPs(r) 7630 (Umckaloabo(r)), an extract from Pelargonium sidoides roots, exerts
      anti-influenza virus activity in vitro and in vivo.
AB  - A prodelphinidin-rich extract from Pelargonium sidoides DC, EPs(r) 7630
      (Umckaloabo(r)), which is licensed to treat respiratory tract infections such as
      acute bronchitis, was investigated for its antiviral effects. EPs(r) 7630 showed
      dose-dependent anti-influenza activity at non-toxic concentrations against
      pandemic H1N1, oseltamivir-sensitive and -resistant seasonal H1N1, seasonal H3N2
      and the laboratory H1N1 strain A/Puerto Rico/8/34, while it had no antiviral
      activity against adenovirus or measles virus. The extract inhibited an early step
      of influenza infection and impaired viral hemagglutination as well as
      neuraminidase activity. However, EPs(r) 7630 did not exhibit a direct virucidal
      effect, as virus preincubation (unlike cell preincubation) with the extract did
      not influence infectivity. Importantly, EPs(r) 7630 showed no propensity to
      resistance development in vitro. Analysis of EPs(r) 7630 constituents revealed
      that prodelphinidins represent the active principle. Chain length influenced
      antiviral activity, as monomers and dimers were less effective than oligo- and
      polymers. Importantly, gallocatechin and its stereoisomer epigallocatechin exert
      antiviral activity also in their monomeric form. In addition, EPs(r) 7630
      administered by inhalation significantly improved survival, body weight and body
      temperature of influenza-infected mice, without obvious toxicity, demonstrating
      the benefit of EPs(r) 7630 in treatment of influenza.

PMID- 22475499
TI  - Endogenous hormone levels and anatomical characters of haustoria in Santalum
      album L. seedlings before and after attachment to the host.
AB  - The physiological and anatomical attributes of haustoria tissues in hemi
      parasitic Santalum album L. seedlings, growing on the potential host, Kuhnia
      rosmarnifolia Vent., were investigated before and after attachment to the host.
      Quantization of endogenous levels of indole-3-acetic acid (IAA), zeatin (Z),
      zeatin riboside (ZR), GA-like substances (GAs) and abscisic acid (ABA) was
      performed by HPLC. Histological preparations were used to characterize structural
      differences between pre- and post-attachment haustoria. The contents of GAs and
      ABA were higher in attached haustoria, with 3.61 and 3.50MUgg(-1) fresh weight,
      respectively, and three times higher than in non-attached haustoria. Cytokinins,
      Z, ZR and IAA levels were also high, and their contents in attached haustoria
      increased 2.04-, 2.17-, and 2.82-fold more, respectively, than in non-attached
      haustoria. A high auxin-to-cytokinin ratio contributed to haustorial development
      of S. album. A numerous amount of starch in parenchyma cells around the
      meristematic region above the haustorial gland and the endophyte tissue of the
      post-attachment haustoria were reported in a Santalaceae member for the first
      time. Many lysosomes were present and large-scale digestion of host cells
      occurred at the interface between the parasite and host. The haustorial
      penetration in S. album into the host stele was suggested to be a function of
      mechanical force and enzymatic activity. Analysis of the endogenous hormone
      levels and the structural characters in S. album haustoria indicated that the
      haustoria were able to synthesize phytohormones, which appeared to be necessary
      for cell division and differentiation during haustorial development. These
      results suggest that endogenous hormones are involved in the haustorial
      development of S. album and in water and nutrient transport in the host-parasite
      association.

PMID- 22475500
TI  - Isolation and characterization of terpene synthases potentially involved in
      flavor development of ripening olive (Olea europaea) fruits.
AB  - The flavor and taste of fruits are often determined by terpenes. We identified
      three cDNAs encoding putative terpene synthases from olive fruits of cv. Frantoio
      and Grignano. Heterologous expression in a bacterial system demonstrated that one
      of the terpene synthases, OeGES1, was an active monoterpene synthase that
      converted geranyl diphosphate to the monoterpene alcohol geraniol. The transcript
      accumulation pattern of this gene showed a peak during fruit ripening in both
      genotypes, indicating that the enzyme may be involved in the production of
      monoterpene flavor compounds in olive fruit. Although the putative terpene
      synthases OeTPS2 and OeTPS3 clustered with alpha-farnesene synthases and
      angiosperm monoterpene synthases, no detectable in vitro activity was found after
      expression in a bacterial system. Nevertheless, their transcripts sharply
      accumulated during fruit ripening starting from veraison.

PMID- 22475501
TI  - Overexpression of thylakoidal ascorbate peroxidase shows enhanced resistance to
      chilling stress in tomato.
AB  - Photosynthesis provides a strong reducing power and a high risk for generation of
      reactive oxygen species (ROS) particularly under chilling stress. Ascorbate
      peroxidases (APXs) reduce H(2)O(2) to water and play an important role in the
      antioxidant system of plants. Though thylakoid ascorbate peroxidase (tAPX) has
      been thought to be key regulator of intracellular levels of H(2)O(2), its
      physiological significance in the response to chilling stress is still under
      discussion. To study the contribution of tAPX to the ROS scavenging, a tomato
      thylakoidal ascorbate peroxidase gene (LetAPX) was isolated and transgenic
      tomatoes were obtained. The LetAPX-GFP fusion protein was targeted to chloroplast
      in Arabidopsis mesophyll protoplast. RNA blotting analysis revealed that the
      LetAPX transcript expression was up-regulated by chilling, high light, exogenous
      salicylic acid (SA) and methyl viologen (MV). Over expression of LetAPX in
      tomatoes conferred tolerance to chilling stress by maintaining higher reduced
      glutathione (GSH) content, chlorophyll and APX activities compared with wild type
      (WT) plants. Furthermore, transgenic plants showed lower levels of hydrogen
      peroxide (H(2)O(2)) and ion leakage, lower malendialdehyde (MDA) content, higher
      net photosynthetic rate (Pn) and higher maximal photochemical efficiency of PSII
      (Fv/Fm). The oxidizable P700 decreased more obviously in WT than that in
      transgenic plants under chilling stress in low irradiance. The results suggested
      that over expression of tAPX played a key role both in alleviating photo
      inhibition of PSI and PSII and enhancing their tolerance to chilling stress.

PMID- 22475502
TI  - Glycerol decreases the integrity of the perinuclear theca in boar sperm.
AB  - We evaluated the effect of glycerol on the perinuclear theca (PT) of boar sperm.
      Samples from six ejaculates obtained from three different boars were incubated in
      the detergent Brij 36-T. Spermatozoa were treated with a glycerol concentration
      of either 2 or 4%, and incubated for 10 or 30 min; two other samples were treated
      with protease inhibitors (PI; leupeptin or an inhibitor commercial cocktail),
      mixed with 4% glycerol, and incubated for 30 min. A third glycerol-free group was
      used as the control. The samples were processed for electron microscopy
      evaluation. The PT remained intact in 78% of the control samples while, after
      addition of glycerol for 30 min, the proportion of spermatozoa with disrupted or
      absent PT increased (P < 0.05). PT was preserved in PI samples, but PT changes
      increased (P < 0.05). Differences due to treatment with glycerol (2 or 4%) at 10
      or 30 min were not observed. These results show, to our knowledge for the first
      time, the adverse effect of glycerol on the integrity of the PT.

PMID- 22475503
TI  - Method to concentrate protein solutions based on dialysis-freezing
      centrifugation: enzyme applications.
AB  - One of the recurrent methodological problems in preparative biochemical work is
      the concentration of dilute protein solutions, including culture supernatants
      resulting from biotechnological processes. A procedure was developed to
      concentrate enzymes by a novel cryoconcentration system. This approach includes a
      new device that facilitates the sample freezing and the subsequent solute elution
      from the frozen matrix by centrifugation. The optimal centrifugation conditions
      for this cryoconcentration system were obtained using whey protein solution as a
      model. The procedure was applied to concentrate dilute solutions of commercial
      pectinase, measuring the endopolygalacturonase (EPG) activity of this enzyme in
      the concentrate by a method based on the on-line torque measurement, and of
      recombinant fructan:fructan 1-fructosyltransferase (1-FFT) protein of Pichia
      pastoris from a culture in a bioreactor, as an expression system. The optimal
      centrifugation speed, time, and temperature were 6150 g, 20 min, and 4  degrees
      C, respectively. The concentration factors for the dilute protein solutions were
      9.2-, 11.2-, and 17.1-fold for 1-FFT, whey, and commercial pectinase,
      respectively. Recoveries ranged from 87% to 93%. The procedure allowed
      concentrating proteins efficiently without affecting their enzymatic activity.

PMID- 22475504
TI  - Gas chromatography-mass spectrometry analysis of 13C labeling in sugars for
      metabolic flux analysis.
AB  - Metabolic flux analysis, using 13C labeled substrates, has become a powerful
      methodology for quantifying intracellular fluxes. Most often, analysis is
      restricted to nuclear magnetic resonance or mass spectrometry measurement of 13C
      label incorporation into protein amino acids. However, amino acid isotopomer
      distribution insufficiently covers the entire network of central metabolism,
      especially in plant cells with highly compartmented metabolism, and analysis of
      other metabolites is required. Analysis of label in saccharides provides
      complementary data to better define fluxes around hexose, pentose, and triose
      phosphate pools. Here, we propose a gas chromatography-mass spectrometry (GC-MS)
      method to analyze 13C labeling in glucose and fructose moieties of sucrose, free
      glucose, fructose, maltose, inositol, and starch. Our results show that
      saccharide labeling for isotopomer quantification is better analyzed by chemical
      ionization than by electron ionization. The structure of the generated fragments
      was simulated and validated using labeled standards. The method is illustrated by
      analysis of saccharides extracted from developing rapeseed (Brassica napus L.)
      embryos. It is shown that glucose 6-phosphate isomerase and plastidial glucose 6
      phosphate transport reactions are not at equilibrium, and light is shed on the
      pathways leading to fructose, maltose, and inositol synthesis.

PMID- 22475505
TI  - Neural correlates of interference inhibition, action withholding and action
      cancelation in adult ADHD.
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) is marked by inhibitory and
      attentional deficits which can persist into adulthood. Those deficits have been
      associated with dysfunctional fronto-striatal and fronto-parietal circuits. The
      present study sought to delineate neural correlates of component specific
      inhibitory deficits in adult ADHD using functional magnetic resonance imaging
      (fMRI). 20 adult ADHD patients and 24 matched healthy controls were included.
      Brain activation was assessed during three stages of behavioral inhibition, i.e.
      interference inhibition (Simon task), action withholding (Go/no-go task) and
      action cancelation (Stop-signal task). Behaviorally, ADHD patients were affected
      in all tasks. Impaired interference inhibition was associated with hypoactivation
      in parietal and medial frontal regions. During action withholding and cancelation
      ADHD patients displayed hypoactivation in a fronto-striatal network. These
      findings support the notion of at least two disturbed neural circuits in ADHD
      differentially associated with deficits in separate inhibitory subcomponents.
      Thereby, deficits in inhibitory subcomponents which are closely connected to
      response interference were related to hypofunction in more attention related
      circuits, while stopping related deficits were rather associated with
      hypofunction in inhibitory circuits.

PMID- 22475506
TI  - PDE inhibition and cognition enhancement.

PMID- 22475507
TI  - Wettability of Nafion and Nafion/Vulcan carbon composite films.
AB  - The wettability of the Pt/carbon/Nafion catalyst layer in proton exchange
      membrane fuel cells is critical to their performance and durability, especially
      the cathode, as water is needed for the transport of protons to the active sites
      and is also involved in deleterious Pt nanoparticle dissolution and carbon
      corrosion. Therefore, the focus of this work has been on the first-time use of
      the water droplet impacting method to determine the wettability of 100% Nafion
      films, as a benchmark, and then of Vulcan carbon (VC)/Nafion composite films,
      both deposited by spin-coating in the Pt-free state. Pure Nafion films, shown by
      SEM analysis to have a nanochanneled structure, are initially hydrophobic but
      become hydrophilic as the water droplet spreads, likely due to reorientation of
      the sulfonic acid groups toward water. The wettability of VC/Nafion composite
      films depends significantly on the VC/Nafion mass ratios, even though Nafion is
      believed to be preferentially oriented (sulfonate groups toward VC) in all cases.
      At low VC contents, a significant water droplet contact angle hysteresis is seen,
      similar to pure Nafion films, while at higher VC contents (>30%), the films
      become hydrophobic, also exhibiting superhydrophobicity, with surface roughness
      playing a significant role. At >80% VC, the surfaces become wettable again as
      there is insufficient Nafion loading present to fully cover the carbon surface,
      allowing the calculation of the Nafion:carbon ratio required for a full coverage
      of carbon by Nafion. 

PMID- 22475508
TI  - Increasing student involvement and learning through using debate as an
      assessment.
AB  - Assessment has long been recognised as the single most influential factor in
      shaping what and how students in higher education choose to learn and the quality
      of learning outcomes depends on the quality of assessment. Within intellectual
      disability nursing the student are prepared within a biopsychosocial educational
      model and curriculum address these challenges. Structured student debates have
      great potential for promoting competence and in-depth knowledge of substantive
      topics relevant to practice. Like other interactive assignments designed to more
      closely resemble real-world activities, issue-oriented debates actively engage
      students in course content. Allowing students to develop and exercise skills that
      translate to practice activities. Most importantly debates help to stimulate
      critical thinking by shaking students free from established opinions and helping
      them to appreciate the complexities involved in practice. This article identifies
      the use of a debate as an assessment method within an intellectual disability
      nursing programme and a student's reflective comment on the process, and their
      experience of a debate as their assessment method.

PMID- 22475509
TI  - Biosynthesis of caffeic acid in Escherichia coli using its endogenous hydroxylase
      complex.
AB  - BACKGROUND: Caffeic acid (3,4-dihydroxycinnamic acid) is a natural phenolic
      compound derived from the plant phenylpropanoid pathway. Caffeic acid and its
      phenethyl ester (CAPE) have attracted increasing attention for their various
      pharmaceutical properties and health-promoting effects. Nowadays, large-scale
      production of drugs or drug precursors via microbial approaches provides a
      promising alternative to chemical synthesis and extraction from plant sources.
      RESULTS: We first identified that an Escherichia coli native hydroxylase complex
      previously characterized as the 4-hydroxyphenylacetate 3-hydroxylase (4HPA3H) was
      able to convert p-coumaric acid to caffeic acid efficiently. This critical
      enzymatic step catalyzed in plants by a membrane-associated cytochrome P450
      enzyme, p-coumarate 3-hydroxylase (C3H), is difficult to be functionally
      expressed in prokaryotic systems. Moreover, the performances of two tyrosine
      ammonia lyases (TALs) from Rhodobacter species were compared after overexpression
      in E. coli. The results indicated that the TAL from R. capsulatus (Rc) possesses
      higher activity towards both tyrosine and L-dopa. Based on these findings, we
      further designed a dual pathway leading from tyrosine to caffeic acid consisting
      of the enzymes 4HPA3H and RcTAL. This heterologous pathway extended E. coli
      native tyrosine biosynthesis machinery and was able to produce caffeic acid (12.1
      mg/L) in minimal salt medium. Further improvement in production was accomplished
      by boosting tyrosine biosynthesis in E. coli, which involved the alleviation of
      tyrosine-induced feedback inhibition and carbon flux redirection. Finally, the
      titer of caffeic acid reached 50.2 mg/L in shake flasks after 48-hour
      cultivation. CONCLUSION: We have successfully established a novel pathway and
      constructed an E. coli strain for the production of caffeic acid. This work forms
      a basis for further improvement in production, as well as opens the possibility
      of microbial synthesis of more complex plant secondary metabolites derived from
      caffeic acid. In addition, we have identified that TAL is the rate-limiting
      enzyme in this pathway. Thus, exploration for more active TALs via bio
      prospecting and protein engineering approaches is necessary for further
      improvement of caffeic acid production.

PMID- 22475512
TI  - Electrosynthesis of a Sc3N@I(h)-C80 methano derivative from trianionic Sc3N@I(h)
      C80.
AB  - The electrosynthetic method has been used for the selective synthesis of
      fullerene derivatives that are otherwise not accessible by other procedures.
      Recent attempts to electrosynthesize Sc(3)N@I(h)-C(80) derivatives using the
      Sc(3)N@I(h)-C(80) dianion were unsuccessful because of its low nucleophilicity.
      Those results prompted us to prepare the Sc(3)N@C(80) trianion, which should be
      more nucleophilic and reactive with electrophilic reagents. The reaction between
      Sc(3)N@C(80) trianions and benzal bromide (PhCHBr(2)) was successful and yielded
      a methano derivative, Sc(3)N@I(h)-C(80)(CHPh) (1), in which the >CHPh addend is
      selectively attached to a [6,6] ring junction, as characterized by MALDI-TOF mass
      spectrometry and NMR and UV-vis-NIR spectroscopy. The electrochemistry of 1 was
      studied using cyclic voltammetry, which showed that 1 exhibits the typical
      irreversible cathodic behavior of pristine Sc(3)N@I(h)-C(80), resembling the
      behavior of other methano adducts of Sc(3)N@I(h)-C(80). The successful synthesis
      of endohedral metallofullerene derivatives using trianionic Sc(3)N@I(h)-C(80) and
      dianionic Lu(3)N@I(h)-C(80), but not dianionic Sc(3)N@I(h)-C(80), prompted us to
      probe the causes using theoretical calculations. The Sc(3)N@I(h)-C(80) trianion
      has a singly occupied molecular orbital with high spin density localized on the
      fullerene cage, in contrast to the highest occupied molecular orbital of the
      Sc(3)N@I(h)-C(80) dianion, which is mainly localized on the inside cluster. The
      calculations provide a clear explanation for the different reactivities observed
      for the dianions and trianions of these endohedral fullerenes.

PMID- 22475511
TI  - Cloning and characterization of three chemosensory proteins from Spodoptera
      exigua and effects of gene silencing on female survival and reproduction.
AB  - Insect chemosensory proteins (CSPs) are supposed to transport hydrophobic
      chemicals to receptors on sensory neurons. However, CSPs are broadly expressed in
      various insect tissues, suggesting their involvement in the physiological
      processes beyond chemoreception. So, the exact physiological roles of CSPs in
      insects still need to be unraveled. In this study, three full-length of CSP genes
      from Spodoptera exigua have been cloned and characterized. The deduced amino acid
      sequences of SexiCSP1, SexiCSP2 and SexiCSP3 revealed open reading frames of 128,
      128 and 126 amino acids, respectively, with four conserved cysteine residues. The
      expression patterns of the three SexiCSPs were further investigated by real-time
      PCR. Three SexiCSPs were expressed in antennae, heads, legs, wings, thoraxes,
      abdomens, testes and ovaries, with the highest expression level in female and
      male antennae. Furthermore, all three SexiCSPs mRNA were distributed extensively
      in the tested development stages with the highest expression level in pupae. RNAi
      based gene silencing study resulted in a dramatic reduction of corresponding mRNA
      in female S. exigua after injection with dsRNA of all three SexiCSPs.
      Consequentially, 42.5% of mortalities, 68.3% (compare to DEPC water injected
      control) and 71.4% (compare to uninjected control) oviposition inhibition, and
      significantly effected egg hatching were observed in the female S. exigua
      injected with dsSexiCSP3 as compared to control treatments. On the other hand,
      dsSexiCSP1 and dsSexiCSP2 injected female adults did not show effects on survival
      and reproduction. Our study confirms the utility of RNAi approach to functional
      characterization of CSP genes in S. exigua and provides a starting point for
      further studies on female survival and reproduction in this insect. It also
      reveals the potential pest controlling method, as insect behavior regulation
      agent that disrupts the expression of chemosensory proteins. 

PMID- 22475513
TI  - Yeast as a powerful model system for the study of apoptosis regulation by protein
      kinase C isoforms.
AB  - Protein kinase C (PKC) is a family of serine/threonine kinases involved in the
      transduction of signals that control different cellular processes, such as cell
      death and proliferation. This family comprises at least 10 isoforms that regulate
      apoptosis in an isoformspecific manner. However, controversial data about the
      role of individual PKC isoforms in apoptosis regulation are frequently reported.
      The co-existence of several PKC isoforms in a same mammalian cell, the distinct
      expression profile of PKC isoforms in different cell types, and the different
      stimulus applied may explain such contradicting results. Therefore major advances
      in the understanding of the molecular mechanisms that regulate the function of
      PKC isoforms in apoptosis are still required. Yeast has proved to be a valuable
      research tool to investigate molecular aspects of apoptosis regulation.
      Additionally, the conservation in yeast of major functional and molecular
      properties of mammalian PKC isoforms favours the use of this simpler cell model
      to uncover relevant aspects of apoptosis regulation by this kinase family. In
      this review, we cover the current knowledge about the role of different PKC
      isoforms in apoptosis. Moreover, we discuss the contribution of yeast to unravel
      several controversial issues about apoptosis regulation by PKC isoforms. The
      exploitation of yeast cells expressing individual PKC isoforms towards the
      identification of isoform-specific PKC modulators is also discussed. The studies
      here summarised highlight that the yeast cell model system can provide valuable
      insights in the PKC research field.

PMID- 22475514
TI  - Multimerization improves targeting of peptide radio-pharmaceuticals.
AB  - Multimerization offers unique kinetic and thermodynamic properties to molecules.
      Multimeric ligands, characterized by multiple similar or different monomeric
      molecules tethered together, can bind several receptors simultaneously.
      Multimerization occurs also in nature. This process can be used to develop
      molecules with high diagnostic and therapeutic value. By altering parameters as
      linkers' length and flexibility, scaffold and backbones insertion, and ligands
      receptors recognition, it is possible to provide high selectivity and binding
      affinity. The resultant multimeric ligand has a more favorable binding affinity
      than corresponding monomeric ligands.

PMID- 22475515
TI  - New trends in reversed-phase liquid chromatographic separations of therapeutic
      peptides and proteins: theory and applications.
AB  - In the pharmaceutical field, there is considerable interest in the use of
      peptides and proteins for therapeutic purposes. There are various ways to
      characterize such complex samples, but during the last few years, a significant
      number of technological developments have been brought to the field of RPLC and
      RPLC-MS. Thus, the present review focuses first on the basics of RPLC for
      peptides and proteins, including the inherent problems, some possible solutions
      and some directions for developing a new RPLC method that is dedicated to
      biomolecules. Then the latest advances in RPLC, such as wide-pore core-shell
      particles, fully porous sub-2 MUm particles, organic monoliths, porous layer open
      tubular columns and elevated temperature, are described and critically discussed
      in terms of both kinetic efficiency and selectivity. Numerous applications with
      real samples are presented that confirm the relevance of these different
      strategies. Finally, one of the key advantages of RPLC for peptides and proteins
      over other historical approaches is its inherent compatibility with MS using both
      MALDI and ESI sources.

PMID- 22475516
TI  - Steroid profiles as potential biomarkers in patients with urogenital tract cancer
      for diagnostic investigations analyzed by liquid chromatography coupled to mass
      spectrometry.
AB  - Large discrepancy remains for the hormone-responsible cancers with regards to the
      conditions generating the optimal opportunity for cancerogenesis. In the
      research, altered steroid profiles were observed in patients with urogenital
      tract cancer diseases, namely bladder, kidney, prostate and testis ones. The
      presented steroid profiles from 154 subjects, including 77 urogenital tract
      cancer patient and 77 healthy controls were determined by liquid chromatography
      coupled to mass spectrometry method. Because the original experimental data
      obtained as a result of analytical experiment in order to interpret them in
      better way required the appropriate pre-treatment, the data were standardized by
      scaling and centering. In order to determine which samples form a collection for
      a high-capacity predictive model, Kennard-Stone's algorithm was used. A principal
      component analysis of preprocessed data provided better consistency of the
      steroid profiles with health status of subjects than PCA profiles without data
      preprocessing and showed a tendency to separate clusters of cancer patients from
      healthy subjects. The discriminant analysis was also performed and the percent of
      correct classification of cancer patients and control group was calculated.
      Finally, detailed studies examined the role of steroid profiles measured in
      urine, and considered as potential biomarkers related to urogenital cancer and
      associated renal dysfunctions.

PMID- 22475517
TI  - Application of a rapid and sensitive liquid chromatography-tandem mass
      spectrometry method for determination of bumetanide in human plasma for a
      bioequivalence study.
AB  - A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) assay has been proposed for the determination of bumetanide in human
      plasma using tamsulosin as internal standard (IS). The analyte and IS were
      extracted from 200 MUL of human plasma via solid phase extraction and the
      chromatographic separation was achieved on Peerless Basic C18 (100 mm * 4.6 mm, 3
      MUm) column under isocratic conditions. Detection of bumetanide and IS was done
      by tandem mass spectrometry, operating in positive ionization and multiple
      reaction monitoring (MRM) acquisition mode. The protonated precursor to product
      ion transitions monitored for bumetanide and IS were m/z 365.2->240.2 and 409.2
      >228.2 respectively. The method was fully validated as per the US FDA guidelines.
      The limit of detection and lower limit of quantitation of the method were 0.03
      and 0.30 ng/mL respectively with a linear dynamic range of 0.30-200.0 ng/mL for
      bumetanide. The intra-batch and inter-batch precision (% CV) was <=6.9% while the
      mean extraction recovery was >90% across quality control levels. The method is
      selective in presence of four diuretic drugs and some commonly used medications
      by healthy volunteers. It was successfully applied to a bioequivalence study of
      2mg bumetanide tablet formulation in 10 healthy Indian male subjects under
      fasting condition. The reproducibility in the measurement of study data was
      demonstrated by reanalysis of 42 incurred samples.

PMID- 22475518
TI  - Rapid HILIC method with fluorescence detection using derivatization reaction
      utilizing o-phthaldialdehyde for determination of degradation product of
      aliskiren.
AB  - A rapid procedure based on direct extraction and HILIC separation of aliskiren
      (ALI) degradation product - 3-amino-2,2-dimethylpropanamide (ADPA) with
      fluorescence detection has been developed. The formation of ADPA from ALI under
      different conditions was studied. The evaluation of HILIC method robustness was
      performed using multifactorial experiments with fixed factors (one-level Plackett
      Burman design). XBridge HILIC column with isocratic elution using mobile phase 10
      mM K(2)HPO(4) pH 7.2-acetonitrile (26:74; v/v) was employed. Fluorescence
      detection after post column derivatization using o-phthaldialdehyde (OPA) reagent
      was performed at excitation and emission wavelength of 345 nm and 450 nm,
      respectively. The reported method has an advantage of a simple sample pre
      treatment and quick and very sensitive measurement. The method was successfully
      applied for the analysis of commercially available ALI samples.

PMID- 22475519
TI  - Factors related with the higher percentage of hospitalizations due to asthma
      amongst women: the FRIAM study.
AB  - INTRODUCTION: The reason why there is a higher hospitalization rate due to asthma
      exacerbations amongst women is unclear. The objective of this study is to explore
      the possible causes that may explain this fact. METHODS: A multi-center,
      prospective study including asthma patients hospitalized in the pulmonary
      medicine departments during a two-year period. By means of a questionnaire, the
      following data were collected: demographic characteristics and treatment
      compliance, anxiety-depression, hyperventilation and asthma control, both prior
      to and during the hospitalization. RESULTS: 183 patients were included, 115
      (62.84%) of whom were women. The women were older (52.4 +/- 18.3/43.4 +/- 18.7;
      P=.02), were more frequently prescribed inhaled corticosteroids (63.2%/47.1%;
      P=.03) and had a higher rate of hyperventilation syndrome (57.3/35.9; P=.02) and
      a longer mean hospital stay (7.3 +/- 3.4/5.9 +/- 3.6; P=.02). The percentage of
      smokers among the women was lower (21.2%/38.8%; p=0.01) and the FEV(1) was lower
      at admittance (58.2% +/- 15.9/67.5% +/- 17.4; P=.03). In the 40 to 60-year-old
      age range, an association was demonstrated between being female and the 'previous
      hospitalizations' variable (OR, 16.1; 95% CI, 1.6-156.7); sex and obesity were
      also independently associated (OR, 4.8; 95% CI, 1.06-22). CONCLUSIONS: In this
      cohort, the rate of hospitalization for asthma was higher in women than in men.
      Being a woman between the ages of 40 and 60 is associated with previous
      hospitalizations and is a risk factor for asthma-related hospitalization. This
      situation could partially be explained by the hormonal changes during menopause,
      where polyposis and obesity are independent risk factors.

PMID- 22475520
TI  - Fruit and vegetable intake: issues with definition and measurement.
AB  - Accurate determination of fruit and vegetable consumption is essential for
      research that seeks to determine current fruit and vegetable intake patterns,
      what type and amount of fruit and vegetable consumption is optimal for human
      health and for evaluating interventions developed to increase such consumption.
      However, there are many issues that make accurate determination of fruit and
      vegetable consumption quite difficult. There are many methods used to measure
      fruit and vegetable intake, but all have limitations. Also, what foods
      individuals consider to be or to not be fruits or vegetables appear to be quite
      variable, with such variability often associated with the individual's
      racial/ethnic background. Researchers and governmental agencies vary with respect
      to what foods they include and do not include when calculating fruit and
      vegetable intake. These differences make it difficult to conduct, evaluate and
      compare studies in this area. The current paper reviews some of the major issues
      with measuring and determining fruit and vegetable intake.

PMID- 22475521
TI  - A successful change of circumstance: a transition state for membrane protein
      folding.
AB  - Knowledge of the transition state is key to understanding a reaction mechanism.
      This vital information has been lacking for integral membrane protein folding,
      but now recent advances have given insight into the structure of their folding
      transition state. This progress has arisen through the successful translation of
      a classical protein engineering method, phi value analysis, from water-soluble
      proteins to the hydrophobic, membrane-embedded protein class. This review covers
      the transition state for the folding of alpha helical membrane proteins. Helix
      formation in the transition state correlates with sequence position and the order
      of transmembrane insertion into the cell membrane, showing that in vitro
      measurements, in entirely different conditions to natural membranes, may reflect
      the cellular situation.

PMID- 22475522
TI  - Association of RAGE gene polymorphisms with type 2 diabetes mellitus, diabetic
      retinopathy and diabetic nephropathy.
AB  - A meta-analysis was performed to assess the associations of the receptor for
      advanced glycation end products (RAGE) gene polymorphisms [Gly82Ser (rs2070600),
      1704G/T (rs184003), 429T/C (rs1800625)] with type 2 diabetes mellitus (T2DM),
      diabetic retinopathy (DR) and diabetic nephropathy (DN). A comprehensive research
      was conducted to identify all case-control or cohort studies. The fixed or random
      effect pooled measure was selected based on the homogeneity test among studies
      that was evaluated with I(2). Meta-regression was used to explore the potential
      sources of between-study heterogeneity. Publication bias was estimated using
      Peters test. Twenty-nine articles were included. Overall, after excluding
      articles deviating from Hardy-Weinberg equilibrium in controls and sensitive
      analysis, no significant association was found between RAGE gene polymorphisms
      (Gly82Ser, 1704G/T, 429T/C) and any of T2DM, DR and DN risk, respectively.
      Subgroup analysis stratified by ethnicity (Asian and Caucasian) also found no
      significant association between the above-mentioned three polymorphisms and T2DM
      risk, respectively. This meta-analysis suggested that there might be no
      association of RAGE gene polymorphisms (Gly82Ser, 1704G/T, 429T/C) with T2DM, DR
      and DN risk.

PMID- 22475523
TI  - Polymorphisms of angiotensin II type 1 receptor gene and those of angiotensinogen
      point at culprit artery in ST-segment elevation myocardial infarction.
AB  - The aim of the study was to determine whether the presence of angiotensin II type
      1 receptor 1166A/C gene polymorphism and two polymorphisms of angiotensinogen,
      namely Met235Thr and Thr174Met, pointed at the culprit artery in patients with ST
      segment elevation myocardial infarction (STEMI). METHODS: The AGTR1 1166A/C
      polymorphism and two AGT gene polymorphisms, Met235Thr and Thr174Met, were
      assessed in 100 patients with STEMI. RESULTS: The odds ratio (OR) of circumflex
      artery (CRX) responsible for STEMI was 3.49 (95% CI: 1.1-10.8, p<0.05) for MetThr
      genotype for AGT Met235Thr gene and 4.54 (95% CI: 1.5-14.2, p<0.01) for ThrMet
      genotype for AGT Thr174Met gene. Homozygous ThrThr genotype for AGT Thr174Met
      gene reduced OR of CRX as culprit artery in STEMI (OR=0.29, 95% CI: 0.1-0.9,
      p<0.05). However, the highest OR that increased up to 13.71 (95% CI: 1.58-119.3)
      was shown in case of right coronary artery and C/C genotype for AGTR1 1166A/C
      gene. CONCLUSIONS: Polymorphism of AGTR1 1166A/C gene can point at the right
      coronary artery as infarct-related artery in STEMI. Polymorphisms of AGT
      Met235Thr and AGT Thr174Met genes are able to mark increased or reduced odds
      ratio of circumflex artery as culprit artery in STEMI.

PMID- 22475524
TI  - Olanzapine and risperidone effects on appetite and ghrelin in chronic
      schizophrenic patients.
AB  - Olanzapine and other second generation antipsychotics have been associated with
      weight gain, which may be related to changes in appetite and food intake.
      However, it is unclear whether changes in appetite in response to treatment with
      second generation antipsychotics are persistent in patients treated chronically
      with these medications and the extent to which changes in appetite are related to
      any continuing weight gain associated with long-term treatment with these drugs.
      In a randomized 5-month study of the effects of olanzapine and risperidone on
      metabolic changes in chronic schizophrenic patients, we assessed appetite changes
      using two scales and correlated appetite changes with weight gain and metabolic
      changes. There is evidence that the hormone ghrelin is related to appetite
      stimulation and falls during satiation after meals, and therefore, may be a
      physiological concomitant indicating appetite changes. We therefore, also
      measured ghrelin before and after a fatty meal at baseline and after 2 months of
      drug treatment. Neither olanzapine nor risperidone increased appetite during the
      5 months of study drug treatment, and there was a trend for a decrease in
      appetite over time. Weight only increased slightly during treatment and changes
      in appetite scores were not correlated with changes in weight or changes in
      glucose or lipids. Fasting ghrelin did not increase in olanzapine- or risperidone
      treated patients, and there were no significant changes in ghrelin responses to a
      fatty meal between baseline and 2 months of drug treatment, and no differences in
      response in olanzapine- vs. risperidone-treated patients. Our findings suggest
      that in chronic schizophrenic patients treated with multiple antipsychotics in
      the past, olanzapine or risperidone do not induce increases in appetite and
      appetite changes are not related to any further small drug-induced weight gain in
      these chronically treated patients. However, it is possible that different
      relationships may exist between appetite and weight changes induced by the
      medications in drug naive patients newly started on olanzapine or risperidone.

PMID- 22475525
TI  - Prevalence and clinical features of Thought-Perception-Sensitivity Symptoms:
      results from a community survey of Korean high school students.
AB  - Epidemiologic research indicates that psychosis and depression most frequently
      develop during adolescence. Hence, an efficient strategy for improving youth
      mental health would be to focus on detection of early-stage psychosis and
      depression in adolescence. In this study, 1461 high school students were surveyed
      using self-report scales. Students who scored equal to or above the cut-off value
      on any of the scales and who agreed to a further examination proceeded to a
      second assessment, using the Kiddie Schedule for Affective Disorders and
      Schizophrenia and Comprehensive Assessment of At-Risk Mental States along with
      self-reporting scales. The estimated prevalence of adolescents at ultra-high risk
      (UHR) for psychosis and of depression-spectrum disorders was 1.26 and 3.69%
      respectively. Compared with the normal group, experiences of bullying, suicidal
      ideation, and suicide attempts were significantly higher in these two groups; the
      subjects at UHR for psychosis were found to have significantly lower academic
      performance and lower ratings on SCRS; and submissive behavior was more prevalent
      in the depression-spectrum group. Our results reveal several clinical features of
      adolescents at UHR for psychosis and with depression-spectrum disorder and
      underscore the importance of accurate assessment of and early appropriate care
      for these adolescents.

PMID- 22475526
TI  - Electrocatalytic properties of prussian blue nanoparticles supported on poly(m
      aminobenzenesulphonic acid)-functionalised single-walled carbon nanotubes towards
      the detection of dopamine.
AB  - Edged plane pyrolytic graphite electrode (EPPGE) was modified with and without
      Prussian blue (PB) nanoparticles and polyaminobenzene sulphonated single-walled
      carbon nanotubes (SWCNTPABS) using the chemical deposition method. The electrodes
      were characterised using microscopy, spectroscopy and electrochemical techniques.
      Results showed that edged plane pyrolytic graphite-single-walled carbon nanotubes
      prussian blue (EPPGE-SWCNT-PB) electrode gave the best dopamine (DA) current
      response, which increases with increasing PB layers. The catalytic rate constant
      of 1.69 * 10(5)mol(-1)cm(3)s(-1), Tafel value of 112 mV dec(-1), and limit of
      detection of DA (2.8 nM) were obtained. Dopamine could be simultaneously detected
      with ascorbic acid. The electrode was found to be electrochemically stable,
      reusable and can be used for the analysis of DA in real drug samples.

PMID- 22475527
TI  - Development of interspecies cloned embryos reconstructed with rabbit (Oryctolagus
      cuniculus) oocytes and cynomolgus monkey (Macaca fascicularis) fibroblast cell
      nuclei.
AB  - Interspecies somatic cell nuclear transfer (ISCNT) has been proposed as a
      technique to produce cloned offspring of endangered species as well as to
      investigate nucleus-cytoplasm interactions in mammalian embryo. However, it is
      still not known which embryo culture medium is optimal for ISCNT embryos for the
      nuclear donor or the oocyte recipient. We assessed the effects of the culture
      medium on the developmental competence of the ISCNT embryos by introducing
      cynomolgus monkey (Macaca fascicularis) fibroblast nuclei into enucleated rabbit
      (Oryctolagus cuniculus) oocytes (monkey-rabbit embryo). The monkey-rabbit ISCNT
      embryos that were cultured in mCMRL-1066 developed to the blastocyst stage,
      although all monkey-rabbit ISCNT embryos cultured in M199 were arrested by the 4
      cell stage. When monkey-rabbit ISCNT and rabbit-rabbit somatic cell nuclear
      transfer (SCNT) embryos were cultured in mCMRL-1066, the blastocyst cell numbers
      of the monkey-rabbit ISCNT embryos corresponded to the cell numbers of the
      control rabbit-rabbit SCNT embryos, which were produced from a rabbit fibroblast
      nucleus and an enucleated rabbit oocyte. In addition, the presence of
      mitochondria, which were introduced with monkey fibroblasts into rabbit recipient
      cytoplasm, was confirmed up to the blastocyst stage by polymerase chain reaction
      (PCR). This study demonstrated that: (1) rabbit oocytes can reprogramme
      cynomolgus monkey somatic cell nuclei, and support preimplantation development;
      (2) monkey-rabbit ISCNT embryos developed well in monkey culture medium at early
      embryonic developmental stages; (3) the cell number of monkey-rabbit ISCNT
      embryos is similar to that of rabbit-rabbit SCNT embryos; and (4) the
      mitochondrial fate of monkey-rabbit ISCNT embryos is heteroplasmic from the time
      just after injection to the blastocyst stage that has roots in both rabbit
      oocytes and monkey fibroblasts.

PMID- 22475528
TI  - A global map of dominant malaria vectors.
AB  - BACKGROUND: Global maps, in particular those based on vector distributions, have
      long been used to help visualise the global extent of malaria. Few, however, have
      been created with the support of a comprehensive and extensive evidence-based
      approach. METHODS: Here we describe the generation of a global map of the
      dominant vector species (DVS) of malaria that makes use of predicted distribution
      maps for individual species or species complexes. RESULTS: Our global map
      highlights the spatial variability in the complexity of the vector situation. In
      Africa, An. gambiae, An. arabiensis and An. funestus are co-dominant across much
      of the continent, whereas in the Asian-Pacific region there is a highly complex
      situation with multi-species coexistence and variable species dominance.
      CONCLUSIONS: The competence of the mapping methodology to accurately portray DVS
      distributions is discussed. The comprehensive and contemporary database of
      species-specific spatial occurrence (currently available on request) will be made
      directly available via the Malaria Atlas Project (MAP) website from early 2012.

PMID- 22475529
TI  - Real time observation and kinetic modeling of the cellular uptake and removal of
      silicon quantum dots.
AB  - The time courses of uptake and removal of silicon quantum dots (Si-QDs) by human
      umbilical endothelial cells (HUVECs) were observed via confocal laser scanning
      microscope. Si-QDs were internalized via endocytosis and transported to late
      endosomes/lysosomes. The number of internalized Si-QDs increased with time and
      gradually reached a plateau value. When Si-QD-internalized HUVECs were
      subsequently washed and exposed to fresh culture medium, HUVECs removed
      internalized Si-QDs via exocytosis. The number of internalized Si-QDs decreased
      with time and gradually reached a plateau value. Not all internalized Si-QDs were
      removed from the cell interior but large numbers of internalized Si-QDs remained
      accumulated inside cells. A kinetic model based on the mass balance of Si-QDs and
      receptors in a cell was proposed to describe the cellular uptake and removal of
      Si-QDs. Model calculation fitted well with experimental results. Using this
      model, the dissociation constant between receptors and Si-QDs in the endosome,
      K(d,in), was found to be a determinant factor for Si-QD accumulation in cells
      after the removal process.

PMID- 22475530
TI  - Comparing predictive drug nephrotoxicity biomarkers in kidney 3-D primary
      organoid culture and immortalized cell lines.
AB  - The cellular microenvironment is recognized to play a key role in stabilizing
      cell differentiation states and phenotypes in culture. This study addresses the
      hypothesis that preservation of in vivo-like tissue architecture in vitro
      produces a cell culture more capable of responding to environmental stimuli with
      clinically relevant toxicity biomarkers. This was achieved using kidney proximal
      tubules in three-dimensional organoid hydrogel culture, with comparisons to
      conventional monolayer kidney cell cultures on plastic. Kidney proximal tubule
      cultures and two immortalized kidney cell line monolayer cultures exposed to
      known nephrotoxic drugs were evaluated for inflammatory cytokines, nephrotoxicity
      associated genes, Kim-1 protein, cytochrome enzymes, and characteristic cellular
      enzyme shedding. Significant similarities are shown for these traditional
      biomarkers of kidney toxicity between in vivo and 3-D organoid endpoints of drug
      toxicity, and significantly, a consistent lack of clinically relevant endpoints
      produced by traditional 2-D kidney cell cultures. These findings impact both in
      vitro bioreactor-based kidney functional and regenerative medicine models, as
      well as high-throughput cell-based drug screening validations.

PMID- 22475531
TI  - Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of
      hepatocyte function.
AB  - Despite recent advances in biomaterial science, there is yet no culture system
      that supports long-term culture expansion of human adult hepatocytes, while
      preserving continued function. Previous studies suggested that acellular liver
      extracellular matrix (ECM), employed as a substrate, improved proliferation and
      function of liver cells. Here we investigated whether extracts prepared from
      acellular liver ECM (liver ECM extract, LEE), or from whole (fresh) liver tissue
      (liver tissue extract, LTE), could be combined with collagen Type I, hyaluronic
      acid (HA), or heparin-conjugated HA (HP) hydrogels to enhance survival and
      functional output of primary human hepatocytes. The liver-specific semi-synthetic
      ECMs (sECMs) were prepared by incorporating LEE or LTE into the gel matrices.
      Subsequently, primary human hepatocytes were maintained in sandwich-style
      hydrogel cultures for 4 weeks. Progressive increase in hepatocyte metabolism was
      observed in all HA and HP groups. Hepatocytes cultured in HA and HP hydrogels
      containing LEE or LTE synthesized and secreted steady levels of albumin and urea
      and sustained cytochrome p450-dependent drug metabolism of ethoxycoumarin.
      Collectively, these results indicate that customized HA hydrogels with liver
      specific ECM components may be an efficient method for expansion human
      hepatocytes in vitro for cell therapy and drug and toxicology screening purposes.

PMID- 22475532
TI  - Heparin-coated superparamagnetic iron oxide for in vivo MR imaging of human MSCs.
AB  - Human mesenchymal stem cells (hMSCs) offer significant therapeutic potential in
      the field of regenerative medicine and high-resolution magnetic resonance imaging
      (MRI) is useful modality to visualize in vivo kinetics of transplanted stem
      cells. For successful MR imaging, there is a great need for effective contrast
      agents for stem cell labeling with high uptake yield and low toxicity. Here, we
      present superparamagnetic iron oxide (SPIO) nanoparticles coated with
      unfractionated heparin (UFH-SPIO) as a new negative contrast agent for in vivo MR
      imaging of hMSCs. The uptake of UFH-SPIO by hMSCs was effective without the aid
      of transfection agents, which was dependent on the concentration and exposure
      time. The uptake efficiency of UFH-SPIO was greater than that of DEX-SPIO (SPIO
      coated with dextran) by approximately 3 folds when treated for 1 h. TEM and
      Prussian blue staining confirmed that UFH-SPIO nanoparticles were internalized
      into the cytosol of hMSCs which existed during in vitro subculture for 28 days.
      Low temperature endocytosis inhibition assay demonstrated that the incorporation
      of UFH-SPIO into hMSCs was likely to be mediated by endocytosis. When the phantom
      of UFH-SPIO-labeled hMSCs was visualized with 3-T T(2)-weighted MRI, the
      hypointensity signals of UFH-SPIO-labeled hMSCs were linearly correlated with the
      concentration of the nanoparticles. The cellular labeling using UFH-SPIO did not
      reduce the viability, proliferation or differentiation potential to osteogenic
      and adipogenic lineages of hMSCs. When the UFH-SPIO-labeled hMSCs were
      transplanted into the left renal subcapsular membranes of nude mice, they were
      successfully visualized and detected by T(2) and T(2)(*)-weighted MRI for a
      month. Collectively, these results suggest that UFH-SPIO nanoparticles are
      promising as a new MRI contrast agent for in vivo long-term tracking of hMSCs.

PMID- 22475533
TI  - Genetic variations in genes involved in heparan sulphate biosynthesis are
      associated with Plasmodium falciparum parasitaemia: a familial study in Burkina
      Faso.
AB  - BACKGROUND: There is accumulating evidence that host heparan sulphate
      proteoglycans play an important role in the life cycle of Plasmodium through
      their heparan sulphate chains, suggesting that genetic variations in genes
      involved in heparan sulphate biosynthesis may influence parasitaemia.
      Interestingly, Hs3st3a1 and Hs3st3b1 encoding enzymes involved in the
      biosynthesis of heparan sulphate are located within a chromosomal region linked
      to Plasmodium chabaudi parasitaemia in mice. This suggests that HS3ST3A1 and
      HS3ST3B1 may influence P. falciparum parasitaemia in humans. METHODS:
      Polymorphisms within HS3ST3A1 and HS3ST3B1 were identified in 270 individuals
      belonging to 44 pedigrees and living in Burkina Faso. Linkage and association
      between parasitaemia and the polymorphisms were assessed with MERLIN and FBAT. A
      genetic interaction analysis was also conducted based on the PGMDR approach.
      RESULTS: Linkage between P. falciparum parasitaemia and the chromosomal region
      containing HS3ST3A1 and HS3ST3B1 was detected on the basis of the 20 SNPs
      identified. In addition, rs28470223 located within the promoter of HS3ST3A1 was
      associated with P. falciparum parasitaemia, whereas the PGMDR analysis revealed a
      genetic interaction between HS3ST3A1 and HS3ST3B1. Seventy-three significant
      multi-locus models were identified after correcting for multiple tests; 37
      significant multi-locus models included rs28470223, whereas 38 multi-locus models
      contained at least one mis-sense mutation within HS3ST3B1. CONCLUSION: Genetic
      variants of HS3ST3A1 and HS3ST3B1 are associated with P. falciparum parasitaemia.
      This suggests that those variants alter both the function of heparan sulphate
      proteoglycans and P. falciparum parasitaemia.

PMID- 22475534
TI  - Type I interferons maintain Foxp3 expression and T-regulatory cell functions
      under inflammatory conditions in mice.
AB  - BACKGROUND & AIMS: Foxp3(+) T-regulatory cells (Tregs) maintain intestinal
      homeostasis under conditions of continuous challenge with inflammatory microbes.
      However, plasticity of the Treg population under certain conditions has been
      reported; Foxp3(+) Tregs can be converted to Foxp3(-) CD4(+) T cells. METHODS: We
      used mice with a T cell-induced colitis model to study the regulatory role of
      type I interferons (IFNs) in adaptive immunity. We transferred CD4(+)CD45RB(hi)
      (RB(hi)) T cells, with or without CD4(+)CD45RB(lo) CD25(+) T cells, from wild
      type or IFN-alphabetaR(-/-) mice into Rag1(-/-) recipients. We analyzed induction
      of colitis by flow cytometry, confocal microscopy, and enzyme-linked
      immunosorbent assay and reverse-transcription polymerase chain reaction analyses.
      IFN-alphabetaR(-/-)Rag(-/-) mice were given injections of recombinant IFN-alpha
      following transfer of IFN-alphabetaR(-/-) RB(hi) T cells and CD4(+)Foxp3(+) cells
      from Foxp3-eGFP mice. RESULTS: Signaling by type I IFNs was required for
      maintenance of Foxp3 expression and the suppressive activity of Tregs in mice.
      Transfer of CD4(+)CD45RB(lo)CD25(+) Tregs from IFN-alphabetaR(-/-) mice did not
      prevent T-cell induction of colitis in mice. Foxp3 expression by Tregs
      transferred from IFN-alphabetaR(-/-) mice was significantly lower than that of
      Tregs from wild-type mice. Administration of recombinant IFN-alpha reduced T cell
      mediated colitis by increasing the number of Foxp3(+) Tregs and their suppressive
      functions. CONCLUSIONS: Type I IFNs regulate intestinal homeostasis by
      maintaining Foxp3 expression on Tregs in colons of mice under inflammatory
      conditions.

PMID- 22475535
TI  - Increased levels of arginase in patients with acute hepatitis B suppress
      antiviral T cells.
AB  - BACKGROUND & AIMS: During viral infection, the activities of virus-specific
      CD8(+) T cells are carefully regulated to prevent severe damage of the infected
      organs. We investigated the mechanisms that control the functions of activated T
      cells. METHODS: We measured the size of the population of activated and
      proliferating CD8(+) T cells and the functional pattern of CD8(+) T cells
      specific for the entire hepatitis B virus proteome and for selected heterologous
      virus (Epstein-Barr virus, human cytomegalovirus, and influenza virus) using
      blood samples from 18 patients with acute hepatitis B. We analyzed the effects of
      different modulatory mechanisms, such as inhibitory molecules, suppressive
      cytokines (interleukin-10), and arginase, on the activities of CD8(+) T cells.
      RESULTS: In patients with acute hepatitis B, the expansion of activated and
      proliferating (HLA-DR/CD38(+), Ki-67(+)/Bcl-2(low)) CD8(+) T cells did not
      quantitatively match their specific functions ex vivo; virus-specific CD8(+) T
      cells had functional impairments that were temporally restricted to the acute
      phase of viral hepatitis. These impairments in function were not limited to HBV
      specific CD8(+) T cells but were also observed in CD8(+) T cells with
      specificities for other viruses. We investigated possible causes of antigen
      independent CD8(+) T cell inhibition and found that the increased levels of
      arginase observed in patients with acute hepatitis could suppress the function of
      activated, but not resting, CD8(+) T cells. CONCLUSIONS: The increased level of
      arginase in patients with acute hepatitis B suppresses the functions of activated
      CD8(+) T cells. This mechanism might limit the amount of liver damage caused by
      activated CD8(+) T cells in patients with acute HBV infection.

PMID- 22475536
TI  - [Unilateral isolated partial third nerve palsy and sphenoiditis in a child: A
      case report].
AB  - We report a case of unilateral mydriasis associated with sphenoid sinusitis and
      mucocele in a child. An 11-year-old girl with a history of unilateral mydriasis
      was referred for ophthalmologic examination. She complained of a mild headache
      over the past four days. The right pupil was dilated and nonreactive to light.
      The left pupil was normal and reactive. There was no ptosis or other focal
      neurological deficit. She was orthotropic. Visual acuity in both eyes, ocular
      motility and fundi were normal. Magnetic resonance imaging (MRI) showed a
      sphenoid sinus mucocele with sphenoiditis. The diagnosis was partial third nerve
      palsy without ophthalmoplegia. Treatment with antibiotics was initiated and led
      to complete resolution of the mydriasis. Sphenoid sinus mucoceles are relatively
      rare. Failure to diagnose and treat can lead to serious neurologic sequellae such
      as third nerve palsy, compressive optic neuropathy, cavernous sinus thrombosis,
      meningitis or brain abscess. Head imaging by reconstructed CT and MRI can lead to
      the diagnosis of mucocele. Isolated unilateral mydriasis as a sign of third nerve
      palsy may be caused by a slowly enlarging lesion. In a child with isolated
      unilateral mydriasis, head MRI should be performed to rule out a compressive
      lesion of the oculomotor nerve.

PMID- 22475537
TI  - [A rare trauma-associated cause of central retinal vein occlusion in a young
      subject].
AB  - INTRODUCTION: Retinal vein occlusions are the second leading cause of retinal
      vascular disease, after diabetic retinopathy. In the case of young subjects, a
      thorough etiological investigation must be conducted in order to diagnose rare
      etiologies, such as this heterozygous mutation of the factor II gene associated
      with a central retinal vein occlusion (CRVO), occurring in a young subject within
      the context of trauma. OBSERVATION: The case deals with a 35-year-old soldier on
      a mission in a conflict zone. He was the victim of blast injury as a result of
      the explosion of an improvised explosive device (IED) or homemade bomb, and
      presented a sudden decline in visual acuity in his left eye associated with the
      clinical picture of a CRVO. Analysis showed a heterozygous factor II G20210A gene
      mutation. CONCLUSION: Retinal vein occlusions are always serious visual events.
      In the case of young subjects, a thorough etiological investigation must be
      conducted in search of rare abnormalities likely to lead to retinal vein
      occlusion.

PMID- 22475538
TI  - [High-resolution spectral-domain OCT images of keratoconus].

PMID- 22475539
TI  - A patent review of sirtuin activators: an update.
AB  - INTRODUCTION: Reversible acetylation is a key post-translational modification of
      target proteins. Sirtuin deacetylases represent the homolog of the yeast silent
      information regulator (SIR2). Although seven sirtuins have been found in mammals,
      all sirtuin activators described to date act through SIRT1. AREAS COVERED: Areas
      covered in this paper include a review of the patent literature associated with
      SIRT1 activators, with a focus on therapeutic applications, primarily related to
      the use of pharmaceuticals and nutraceuticals containing resveratrol (RSV), and
      the development of second-generation activators unrelated to RSV. Also discussed
      is the current controversy over whether or not these molecules are actual SIRT1
      activators. EXPERT OPINION: Developing effective strategies to protect against
      diet-induced metabolic imbalance is necessary to fight against current obesity
      rates. The hypothalamus is a candidate for developing drugs that suppress SIRT1
      degradation, as a strategy for treating metabolic syndrome. Deciphering the basic
      mechanism of activators is essential to develop effective strategies to alter
      sirtuin activity. This is true regardless of the apparent controversy of whether
      in vitro activation of SIRT1 is direct or not, depending on the experimental
      design, and whether sirtuins may play a major role in longevity. The numerous
      studies on their positive effects against age-related diseases, obesity and other
      metabolic disorders are still valid, promising to positively influence the
      development of treatments to improve human health.

PMID- 22475540
TI  - Supreme Court arguments on the ACA--a clash of two world views.

PMID- 22475541
TI  - Circadian discrimination of reward: evidence for simultaneous yet separable food-
      and drug-entrained rhythms in the rat.
AB  - A unique extra-suprachiasmatic nucleus (SCN) oscillator, operating independently
      of the light-entrainable oscillator, has been hypothesized to generate feeding
      and drug-related rhythms. To test the validity of this hypothesis, sham-lesioned
      (Sham) and SCN-lesioned (SCNx) rats were housed in constant dim-red illumination
      (LL(red)) and received a daily cocaine injection every 24 h for 7 d (Experiment
      1). In a second experiment, rats underwent 3-h daily restricted feeding (RF)
      followed 12 d later by the addition of daily cocaine injections given every 25 h
      in combination with RF until the two schedules were in antiphase. In both
      experiments, body temperature and total activity were monitored continuously.
      Results from Experiment 1 revealed that cocaine, but not saline, injections
      produced anticipatory increases in temperature and activity in SCNx and Sham
      rats. Following withdrawal from cocaine, free-running temperature rhythms
      persisted for 2-10 d in SCNx rats. In Experiment 2, robust anticipatory increases
      in temperature and activity were associated with RF and cocaine injections;
      however, the feeding periodicity (23.9 h) predominated over the cocaine
      periodicity. During drug withdrawal, the authors observed two free-running
      rhythms of temperature and activity that persisted for >14 d in both Sham and
      SCNx rats. The periods of the free-running rhythms were similar to the feeding
      entrainment (period = 23.7 and 24.0 h, respectively) and drug entrainment (period
      = 25.7 and 26.1 h, respectively). Also during withdrawal, the normally close
      correlation between activity and temperature was greatly disrupted in Sham and
      SCNx rats. Taken together, these results do not support the existence of a single
      oscillator mediating the rewarding properties of both food and cocaine. Rather,
      they suggest that these two highly rewarding behaviors can be temporally
      isolated, especially during drug withdrawal. Under stable dual-entrainment
      conditions, food reward appears to exhibit a slightly greater circadian influence
      than drug reward. The ability to generate free-running temperature rhythms of
      different frequencies following combined food and drug exposures could reflect a
      state of internal desynchrony that may contribute to the addiction process and
      drug relapse.

PMID- 22475542
TI  - Maternal effects shape dynamic trajectories of reproductive allocation in the
      ladybird Coleomegilla maculata.
AB  - We followed lifetime trajectories of reproductive allocation in Coleomegilla
      maculata females of three different size classes produced by rearing beetles on
      three different daily larval feeding regimes (30 min, 6 h or ad libitum access to
      eggs of Ephestia kuehniella). We hypothesized that small females would produce
      fewer and smaller eggs than larger females and that reproductive effort would
      decline with female age. Females were mated with a male from the same treatment
      and then isolated with ad libitum food for their entire adult lives. Egg size
      increased over time in all treatments; small females started off laying the
      smallest eggs, but increased egg size more rapidly than larger females, until all
      treatments converged on a similar egg size around the 20th day of oviposition.
      Large females realized a larger proportion of their fecundity early in life, but
      smaller females increased daily fecundity over time. Reproductive effort (egg
      mass/body mass) did not decline over 30 oviposition days; it remained constant in
      large females, but increased among small and medium females, suggesting gradual
      compensation for larval food deprivation. An increase in egg size with maternal
      age may be an adaptive strategy to maximize fitness on ephemeral patches of aphid
      prey, assuming females reproduce in a single aphid outbreak and that offspring
      produced later in the aphid cycle experience greater competition and risk of
      mortality compared to those produced earlier. We demonstrate for the first time
      in Coleoptera that dynamic changes in both egg size and number occur as a
      function of female age and illustrate that such changes are constrained by larval
      feeding histories via their effects on maternal body size. 

PMID- 22475543
TI  - Military walking blood bank and the civilian blood service.
AB  - In most countries whole blood transfusions have been replaced by component
      therapy. This has allowed for both better usage of the blood donations and better
      quality during storage. While this strategy was initially motivated by the
      commercial need for plasma the plasma reduction also reduced the levels of low
      grade proteases and sialidase, hence minimizing the cellular storage
      lesion/microvesiculation during prolonged storage. Plasma reduction also reduces
      transfusion reactions associated with plasma. During special military conditions,
      however, blood transfusion is urgently needed without corresponding access to
      blood components, in particular platelets. Accordingly, new focus on whole blood
      has aroused and added a new challenge to the blood transfusion services. This
      special issue of "what is happening" highlights the planed efforts by Swedish and
      Norwegian groups in the developments of military walking blood bank, which is
      applicable to civil blood services.

PMID- 22475544
TI  - Investigation of a new in-line leukocyte reduction filter for packed red blood
      cells.
AB  - BACKGROUND AND OBJECTIVES: Occasionally there are adverse transfusion reactions
      in the therapeutic use of packed red blood cells. Some of those reactions are
      caused by the presence of white blood cells (WBCs). Both immunogenic and
      infectious transfusion reactions are significantly influenced by the level of
      white blood cell contamination. MATERIALS AND METHODS: The flexible in-line red
      cell filtration system Leucoflex LCR Diamond (Macopharma) was investigated.
      According to manufacturer information the system has a smaller filter surface (46
      cm(2)) than the previous filter LCR-5 (53 cm(2)). Main difference with the
      previous model is the rhomboid design. The filter tube connections are not at the
      level of the centre edge, but at two opposite corners. Eighteen red cell
      concentrates were produced under Good Manufacturing Practice conditions in
      routine operation. To ensure the quality of the filter system every 7 days
      metabolic parametres such as WBC count, haemoglobin content, haemolysis rate,
      potassium load, pH and ATP content were analysed over a storage period of 49
      days. RESULTS: The mean product volume was 260.7 mL after filtration. Average
      haemoglobin content was 51.8 g per unit and WBC contamination was 0.02 * 10(6)per
      unit. Haemolysis rate was 0.05% directly after filtration and 0.20% at the end of
      storage. Immediately after filtration the potassium concentration was 1.3 mmol/L
      and the pH was 7.37. During whole storage time the ATP level was maintained above
      2.0 MUmol per g haemoglobin. CONCLUSION: The tested filtration system is suitable
      for quality-assured production of red blood cell concentrates meeting national
      and international guidelines.

PMID- 22475545
TI  - The TITAN trial--assessing the efficacy and safety of an anti-von Willebrand
      factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura.
AB  - The Phase II TITAN trial is designed to assess the efficacy and safety of an anti
      von Willebrand factor (vWF) Nanobody in patients with acquired thrombotic
      thrombocytopenic purpura (TTP). Nanobodies are a novel class of therapeutic
      proteins and are based on the smallest functional fragments of single-chain
      antibodies that occur naturally in the Camelidae family (Nanobody(r) and
      Nanobodies(r) are registered trademarks of Ablynx NV). With vWF implicated in the
      thrombotic process underlying TTP, an anti-vWF Nanobody may hold significant
      promise as adjunctive therapy to plasma exchange. Recruitment is currently
      ongoing, and aims to include a total of 110 patients from countries in Europe,
      the Middle East, Australia and Northern America.

PMID- 22475546
TI  - Transfusion induced Graft versus host disease - Case report in a 2 year child.
AB  - Graft-versus-host disease (GVHD) is a rare, almost always fatal complication of a
      blood transfusion. It occurs much more commonly after bone marrow
      transplantation, a setting in which it is less severe-mortality rate of 20-25%
      following transplantation versus 80-90% when associated with a transfusion.
      Transfusion associated GVHD occurs in two settings: when the recipient is
      immunodeficient; and when there is a specific type of partial HLA matching
      between the donor and recipient. Here we present a case of transfusion associated
      GVHD which developed when a 2 year old immunocompetent girl was given whole blood
      which was taken by his father. Inspite of very intense therapy with parental
      steroids and oral cyclosporine the child succumbed to death.

PMID- 22475547
TI  - Solid Phase Red Cell Adherence Assay: a tubeless method for pretransfusion
      testing and other applications in transfusion science.
AB  - Solid Phase Red Cell Adherence Assay (SPRCA) is one of the two tubeless methods
      developed to improve sensitivity and specificity in blood group serology. The
      SPRCA (solid phase) and the column agglutination (gel) technology have gained
      wide acceptance following successful adaptation to fully automated platforms, The
      purpose of this paper is to discuss the development, principle, procedures as
      well as laboratory and clinical applications of the SPRCA in transfusion
      medicine.

PMID- 22475548
TI  - Anisotropic magnetoresistance and piezoresistivity in structured Fe3O4-silver
      particles in PDMS elastomers at room temperature.
AB  - Magnetorheological elastomers, MREs, based on elastic organic matrices displaying
      anisotropic magnetoresistance and piezoresistivity at room temperature were
      prepared and characterized. These materials are dispersions of superparamagnetic
      magnetite forming cores of aggregated nanoparticles inside silver microparticles
      that are dispersed in an elastomeric polymer (poly(dimethylsiloxane), PDMS),
      curing the polymer in the presence of a uniform magnetic field. In this way, the
      elastic material becomes structured as the application of the field induces the
      formation of filaments of silver-covered inorganic material agglomerates
      (needles) aligned in the direction of the field (parallel to the field). Because
      the magnetic particles are covered with silver, the MREs are not only magnetic
      but also electrical conductors. The structuration induces elastic, magnetic, and
      electrical anisotropic properties. For example, with a low concentration of
      particles in the elastic matrix (5% w/w) it is possible to obtain resistances of
      a few ohms when measured parallel to the needles or several megaohms in the
      perpendicular direction. Magnetite nanoparticles (Fe(3)O(4) NP) were synthesized
      by the coprecipitation method, and then agglomerations of these NPs were covered
      with Ag. The average size of the obtained magnetite NPs was about 13 nm, and the
      magnetite-silver particles, referred to as Fe(3)O(4)@Ag, form micrometric
      aggregates (1.3 MUm). Nanoparticles, microparticles, and the MREs were
      characterized by XRD, TEM, SEM, EDS, diffuse reflectance, voltammetry, VSM, and
      SQUID. At room temperature, the synthesized magnetite and Fe(3)O(4)@Ag particles
      are in a superparamagnetic state (T(B) = 205 and 179 K at 0.01 T as determined by
      SQUID). The elastic properties and Young's modulus of the MREs were measured as a
      function of the orientation using a texture analysis device. The magnetic
      anisotropy in the MRE composite was investigated by FMR. The electrical
      conductivity of the MRE (sigma) increases exponentially when a pressure, P, is
      applied, and the magnitude of the change strongly depends on what direction P is
      exerted (anisotropic piezoresistivity). In addition, at a fixed pressure, sigma
      increases exponentially in the presence of an external magnetic field (H) only
      when the field H is applied in the collinear direction with respect to the
      electrical flux, J. Excellent fits of the experimental data sigma versus H and P
      were achieved using a model that considers the intergrain electron transport
      where an H-dependent barrier was considered in addition to the intrinsic
      intergrain resistance in a percolation process. The H-dependent barrier decreases
      with the applied field, which is attributed to the increasing match of spin
      polarization in the silver covers between grains. The effect is anisotropic
      (i.e., the sensitivity of the magnetoresistive effect is dependent on the
      relative orientation between H and the current flow J). In the case of Fe(3)O(4)@
      Ag, when H and J are parallel to the needles in the PDMS matrix, we obtain
      changes in sigma up to 50% for fields of 400 mT and with resistances on the order
      of 1-10 Omega. Magnetoresistive and magnetoelastic properties make these
      materials very interesting for applications in flexible electronics, electronic
      skins, anisotropic pressure, and magnetic field sensors.

PMID- 22475549
TI  - Early-life stress and recurrent psychological distress over the lifecourse
      predict divergent cortisol reactivity patterns in adulthood.
AB  - Early-life stress (ELS) is associated with substantially increased lifetime risk
      for recurrent psychological problems, with evidence indicating that dysregulation
      of the physiological stress reactivity system may be partly responsible. However,
      some ELS-exposed people remain psychologically resilient. Although two distinct
      patterns of hypothalamic-pituitary-adrenal axis (HPA) stress reactivity have been
      observed in ELS-exposed samples (hyper- and hypo-reactive), the hypothesis that
      these patterns may be associated with long-term history of psychological problems
      has not been explored. We used healthy Whitehall II study subjects (n=543) who
      participated in the 2008 Heart Scan Study (HSS) to assess salivary cortisol
      responses to a cognitive stressor, ELS exposure, and other psychosocial factors.
      Mean age of the sample at the HSS was 63 years. HSS data were linked to nearly 20
      years of participants' Whitehall data, including repeated measures of
      psychological distress (GHQ-28). Piecewise growth curve analyses revealed that
      ELS-exposed persons with a history of recurrent psychological distress in
      adulthood had significantly blunted cortisol reactivity compared to non-ELS
      exposed participants, while ELS-exposed persons with little or no history of
      distress had significantly elevated baseline cortisol, prolonged responses, and
      greater total cortisol production. Our findings indicate that for ELS-exposed
      individuals, different trajectories in psychological health over their adult
      lifetimes predict different cortisol reactivity patterns. These findings have
      important implications for our understanding of ELS-related mental health risk
      and treatment of these disorders.

PMID- 22475550
TI  - Insights into aquatic toxicities of the antibiotics oxytetracycline and
      ciprofloxacin in the presence of metal: complexation versus mixture.
AB  - Co-contamination of ligand-like antibiotics (e.g., tetracyclines and quinolones)
      and heavy metals prevails in the environment, and thus the complexation between
      them is involved in environmental risks of antibiotics. To understand
      toxicological significance of the complex, effects of metal coordination on
      antibiotics' toxicity were investigated. The complexation of two antibiotics,
      oxytetracycline and ciprofloxacin, with three heavy metals, copper, zinc, and
      cadmium, was verified by spectroscopic techniques. The antibiotics bound metals
      via multiple coordination sites and rendered a mixture of various complexation
      speciations. Toxicity analysis indicated that metal coordination did modify the
      toxicity of the antibiotics and that antibiotic, metal, and their complex acted
      primarily as concentration addition. Comparison of EC(50) values revealed that
      the complex commonly was highest toxic and predominately correlated in toxicity
      to the mixture. Finally, environmental scenario analysis demonstrated that
      ignoring complexation would improperly classify environmental risks of the
      antibiotics.

PMID- 22475551
TI  - A multi-technique investigation of copper and zinc distribution, speciation and
      potential bioavailability in biosolids.
AB  - The use of biosolids in agriculture continues to be debated, largely in relation
      to their metal contents. Our knowledge regarding the speciation and
      bioavailability of biosolids metals is still far from complete. In this study, a
      multi-technique approach was used to investigate copper and zinc speciation and
      partitioning in one contemporary and two historical biosolids used extensively in
      previous research and field trials. Using wet chemistry and synchrotron
      spectroscopy techniques it was shown that copper/zinc speciation in the biosolids
      was largely equivalent despite the biosolids being derived from different
      countries over a 50 year period. Furthermore, copper speciation was consistently
      dominated by sorption to organic matter whereas Zn partitioned mainly to iron
      oxides. These data suggest that the results of historical field trials are still
      relevant for modern biosolids and that further risk assessment studies should
      concentrate particularly on Cu as this metal is associated with the mineralisable
      biosolids fraction.

PMID- 22475552
TI  - Characterization of pyrimidine nucleoside phosphorylase of Mycoplasma hyorhinis:
      implications for the clinical efficacy of nucleoside analogues.
AB  - In the present paper we demonstrate that the cytostatic and antiviral activity of
      pyrimidine nucleoside analogues is markedly decreased by a Mycoplasma hyorhinis
      infection and show that the phosphorolytic activity of the mycoplasmas is
      responsible for this. Since mycoplasmas are (i) an important cause of secondary
      infections in immunocompromised (e.g. HIV infected) patients and (ii) known to
      preferentially colonize tumour tissue in cancer patients, catabolic mycoplasma
      enzymes may compromise efficient chemotherapy of virus infections and cancer. In
      the genome of M. hyorhinis, a TP (thymidine phosphorylase) gene has been
      annotated. This gene was cloned, expressed in Escherichia coli and kinetically
      characterized. Whereas the mycoplasma TP efficiently catalyses the phosphorolysis
      of thymidine (Km=473 MUM) and deoxyuridine (Km=578 MUM), it prefers uridine
      (Km=92 MUM) as a substrate. Our kinetic data and sequence analysis revealed that
      the annotated M. hyorhinis TP belongs to the NP (nucleoside phosphorylase)-II
      class PyNPs (pyrimidine NPs), and is distinct from the NP-II class TP and NP-I
      class UPs (uridine phosphorylases). M. hyorhinis PyNP also markedly differs from
      TP and UP in its substrate specificity towards therapeutic nucleoside analogues
      and susceptibility to clinically relevant drugs. Several kinetic properties of
      mycoplasma PyNP were explained by in silico analyses.

PMID- 22475553
TI  - Association of microtubule associated protein-2, synaptophysin, and
      apolipoprotein E mRNA and protein levels with cognition and anxiety levels in
      aged female rhesus macaques.
AB  - The dendritic protein microtubule associated protein 2 (MAP-2), the presynaptic
      marker synaptophysin (SYN), and apolipoprotein E (APOE), a protein which plays a
      role in lipid transport and metabolism and affects synaptic activity show changes
      with age. We analyzed post-mortem tissue from aged female rhesus macaques
      cognitively tested in a spatial maze and classified as good spatial performers
      (GSP) or poor spatial performers (PSP) and behaviorally tested in a playroom and
      classified as bold or reserved animals. MAP2, SYN, and APOE mRNA and protein
      levels in the prefrontal cortex (PFC), hippocampus, and amygdala, were assessed
      using qRT-PCR and western blot. In the amygdala, bold monkeys had higher levels
      of MAP2 and SYN mRNA than reserved monkeys. MAP2 mRNA correlated positively with
      amygdala size on the right, left, and combined left and right sides, while SYN
      mRNA levels correlated positively with the size of the right amygdala. In the
      hippocampus, SYN and APOE protein levels were higher in GSP than PSP animals.
      Thus, in aged nonhuman primates, classification of measures of anxiety is
      associated with differences in selected mRNA, but not protein, levels. In
      contrast, classification of cognitive performance is associated with differences
      in selected protein, but not mRNA, levels.

PMID- 22475554
TI  - Rats learn to freeze to 22-kHz ultrasonic vocalizations through autoconditioning.
AB  - Rats emit ultrasonic vocalizations (USVs) at ~22kHz and ~50kHz, respectively,
      during negative and positive affective states. Among rats raised in a
      naturalistic social context, 22-kHz USVs serve as "alarm cries" that can elicit
      freezing behavior. By contrast, several studies show that naive laboratory rats
      do not freeze in response to alarm cries. An obvious and consistent
      interpretation of these facts is that USV-elicited freezing depends on a type of
      social learning that ordinarily does not occur in the laboratory. However, the
      present study explored an alternative and explicitly non-social learning
      mechanism. Animals in the experimental group received multiple footshocks that
      elicited 22-kHz USVs. Animals in the control group were exposed to the same
      chamber but did not receive footshocks and, therefore, did not vocalize. When
      subsequently tested in a novel context, experimental animals froze in response to
      a novel 22-kHz USV but were unresponsive to a novel 50-kHz USV. Vocalizing during
      the aversive experience was predictive of subsequent freezing to the 22-kHz USV.
      As expected from previous studies, control animals failed to freeze to either
      USV. We propose that the experimental animals learned to associate their own 22
      kHz USVs with an internal fear state and selectively generalized this
      "autoconditioning" to a novel 22-kHz USV. This non-social form of learning seems
      sufficiently rapid, reliable, and stimulus-specific to be ethologically adaptive.

PMID- 22475555
TI  - Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal
      carcinomatosis: prognosis and treatment of recurrences in a cohort study.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC)
      treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but
      controversy remains. The primary aims were to analyse the outcome and prognostic
      variables of colorectal PC patients treated with CRS and IPC, and to report on
      the outcome of additional surgical treatments of subsequent recurrences. METHODS:
      Patients referred for treatment of colorectal PC between 1996 and 2010 were
      included in a cohort. The following data was collected: clinicopathological
      parameters, survival, recurrences, perioperative chemotherapy and type of IPC
      (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative
      intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on
      potential prognostic factors for overall survival (OS). RESULTS: In the 151
      patient cohort, the median OS was 34 months (range: 2-77) for CRS and HIPEC with
      five-year survival predicted at 40% (five-year disease-free survival 32%). For
      CRS and SPIC, the OS was 25 months (range: 2-188) with five-year survival at 18%.
      Open-and-close patients survived 6 months (range: 0-14) with no five-year
      survival (HIPEC vs. SPIC p = 0.047, SPIC vs. open-and-close p < 0.001). Adjuvant
      systemic chemotherapy was a noteworthy independent prognostic factor in the
      multivariable analysis. OS for patients undergoing additional surgical treatment
      of recurrences was 25 months vs. 10 months with best supportive care or
      palliative chemotherapy (p = 0.01). CONCLUSION: Substantial long-term survival is
      possible in patients with colorectal PC. HIPEC was associated with better OS than
      SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good
      OS is achievable in selected patients undergoing additional surgical treatment of
      isolated liver or peritoneal recurrences after prior complete CRS.

PMID- 22475556
TI  - Cerebrospinal fluid 5-hydroxyindolacetic acid correlates directly with negative
      affective intensity, but not affective lability, in human subjects.
AB  - Centrally acting monoamines have long been thought to be associated with
      component traits of behavior and emotion and are potential biological mediators
      of psychopathology. In this study we tested the hypothesis that centrally acting
      monoamines would be associated with measures of affective instability (i.e.
      affective intensity and affective lability) in healthy and personality disordered
      human subjects. In total, 57 adult subjects including 19 psychiatrically healthy
      volunteers and 38 personality disordered individuals were assessed for affective
      instability with the affective intensity measure (AIM) and the Affective Lability
      Scale (ALS). Samples of cerebrospinal fluid (CSF) were collected for assay of 5
      hydroxyindoleacitic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4
      hydroxy-phenylglycol (MHPG). CSF 5-HIAA concentration correlated directly with
      overall AIM score and, specifically, with the AIM Negative Intensity score, in
      all subjects and in personality disordered subjects. This result was not affected
      but the addition of aggression scores or life history of mood disorder to the
      model. Neither CSF HVA nor MHPG were found to uniquely correlate with either AIM
      or ALS measure. Higher Affective Intensity scores, Negative Intensity scores,
      specifically, are directly correlated with higher basal levels of CSF 5-HIAA.
      This relationship was independent of aggression, life history of mood disorder
      and general personality traits.

PMID- 22475557
TI  - Synthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin
      7(3H)-ones as novel series of potent beta isoform selective phosphatidylinositol
      3-kinase inhibitors.
AB  - A series of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones with excellent enzyme
      inhibition, improved isoform selectivity, and excellent inhibition of downstream
      phosphorylation of AKT has been identified. Several compounds in the series
      demonstrated potent (~ 0.100 MUM IC(50)) growth inhibition in a PTEN deficient
      cancer cell line.

PMID- 22475558
TI  - Discovery of an orally-bioavailable CC Chemokine Receptor 2 antagonist derived
      from an acyclic diaminoalcohol backbone.
AB  - We describe an isostere-driven approach to improve upon a previously-described
      series of capped dipeptide antagonists of CC Chemokine Receptor 2 (CCR2).
      Modification of the substitution around the isostere was combined with additional
      changes in a distal aromatic substituent to provide single-digit nanomolar
      antagonists of CCR2. These studies led to the identification of 18, a compound
      that was suitable for studies in murine models of CCR2 activity.

PMID- 22475559
TI  - Synthesis and characterization of pyruvate-isoniazid analogs and their copper
      complexes as potential ICL inhibitors.
AB  - Currently used anti-tubercular drugs target actively growing Mycobacterium
      tuberculosis (Mtb) but there are no current therapies targeting persistent
      mycobacteria. Isocitrate lyase (ICL) is an important enzyme of the glyoxylate
      shunt pathway used by Mtb for sustaining intracellular infection in inflammatory
      macrophages under conditions of stress such as nutrient depletion and anaerobic
      metabolism. Since the humans do not possess this enzyme it constitutes an
      attractive target for selective drug design. Present work describes synthesis and
      structural characterization of pyruvate-isoniazid conjugates and their copper
      complexes with potent anti-tubercular activities against M. tuberculosis H37Rv.

PMID- 22475560
TI  - Design and synthesis of carbamate and thiocarbamate derivatives and their
      inhibitory activities of NO production in LPS activated macrophages.
AB  - Series of carbamate and thiocarbamate derivatives were designed and synthesized
      and their inhibitory activities of NO production in lipopolysaccharide-activated
      macrophages were evaluated. Several thoicarbamate derivatives revealed promising
      inhibitory activity. The structure-activity relationship study of these compounds
      is also reported. Among these compounds, compound 12b was the most potent with
      6.5 MUM of IC(50). They inhibited NO production through the suppression of iNOS
      protein and mRNA expression and nuclear translocation of p65.

PMID- 22475561
TI  - Synthesis and inhibitory effect of piperine derivates on monoamine oxidase.
AB  - A series of piperine derivates (1-19) have been designed, synthesized and
      evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity
      and selectivity. It is worth noting that most of the small amine moieties
      substituted on the piperidine ring proved to be potent and selective inhibitors
      of MAO-B rather than of MAO-A. 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic
      acid n-propyl amide (3) showed the greatest MAO-B inhibitory activity (IC(50)(MAO
      B)=0.045 MUM) and good selectivity (IC(50)(MAO-A)=3.66 MUM). The conjugated
      double bond and carbonyl group of piperine are proved to be an essential feature
      for piperine and related alkylamides to exhibit MAO-inhibitory activity. Binding
      mode of the titled compounds was predicted using FlexX algorithm. The design and
      optimization of novel small molecule monoamine oxidase inhibitors will be guided
      by the results of this report.

PMID- 22475562
TI  - beta-Glucosidase involvement in the formation and transformation of oleuropein
      during the growth and development of olive fruits (Olea europaea L. cv.
      Arbequina) grown under different farming practices.
AB  - The present study investigates oleuropein metabolism, as well as the involvement
      of beta-glucosidase during the growth, development, and ripening of olive fruit.
      The results show that in olive fruit the in vivo formation and transformation of
      oleuropein takes place in three different stages. The first one is characterized
      by a net accumulation of oleuropein and occurs in the immature fruit. In the
      second stage, associated with the green and light-green fruits, oleuropein
      content is maintained practically constant, and finally, a third stage that
      begins in the green-yellow fruit is characterized by a progressive decline of the
      oleuropein concentration. Our findings confirm that in the absence of beta
      glucosidase the Damtoft-proposed pathway is active and that net synthesis of
      oleuropein is unquestionable. beta-Glucosidase activity plays a key role in the
      oleuropein metabolism catalyzing its in vivo hydrolysis.

PMID- 22475563
TI  - Minor changes in serum levels of cytokines after removal of amalgam restorations.
AB  - Dental amalgam restorations release mercury and silver which is absorbed and
      distributed in the body. Animal studies have shown that both elements may
      interfere with the host by activation of the immune system in genetically
      susceptible strains at exposure levels relevant to those from dental amalgam
      restorations. The aim of this study was to test the hypothesis of no change over
      time in concentrations of a number of immune mediators in serum after removal of
      all dental amalgam restorations in patients with health complaints attributed to
      their amalgam restorations and compare with a healthy reference group. Twenty
      patients previously examined at a specialty unit for health complaints attributed
      to dental materials were included in a clinical trial and had all amalgam
      restorations replaced with other dental restorative materials. Serum samples were
      collected before amalgam removal and 3 and 12 months after the removal was
      finished. Twenty blood donors matched for age and gender were used as comparison
      group. A fluorescent bead-based (Luminex) immunoassay kit was used to measure
      cytokines, chemokines and growth factors in serum. At baseline, the patient group
      had slightly higher values for GM-CSF, IL-6, IL-2R, IFN-alpha, IL-7, and IL
      12p40/p70 compared with the reference group. After amalgam removal a decrease
      towards the median value of the reference group was found for GM-CSF, IL-8, and
      IL-7. In conclusion, removal of all dental amalgam restorations and replacement
      with other dental restorative materials was associated with decreased
      concentrations of Th1-type proinflammatory markers in serum.

PMID- 22475564
TI  - Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma
      differentiation and progression.
AB  - PURPOSE: Cell division cycle 20 (CDC20) homolog is an anaphase-promoting complex
      activator that is essential for cell division, but whether its expression in
      pancreatic ductal adenocarcinoma (PDAC) is significant is unknown. In this
      retrospective study, we determined whether aberrant CDC20 expression can be used
      as a biomarker in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and
      whether its expression reflects clinical progression. EXPERIMENTAL DESIGN: We
      compared CDC20 expression levels in normal, cancerous, and inflamed pancreatic
      tissues from stage II PDAC patients with clinical outcomes and determined CDC20
      levels in seven PDAC cell lines. CDC20 was identified using a cDNA microarray
      database containing gene expression profiles for PDAC tissues and cell lines and
      chronic pancreatitis and normal pancreas tissues. Its expression was confirmed by
      real-time quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR).
      An immunohistochemical analysis of tissue microarrays from resected PDAC tumors
      and paired benign pancreatic tissues was done and CDC20 levels were correlated
      with clinical outcome. RESULTS: Fifty-six patients were included in this study. A
      microarray analysis revealed 5-fold higher CDC20 expression in PDAC tissue than
      in chronic pancreatitis tissue. A qRT-PCR analysis confirmed a mean 20-fold
      higher CDC20 level in PDAC tissue than in normal pancreas and pancreatitis
      tissue. RNA and protein CDC20 expression was detected in several PDAC cell lines.
      An immunohistochemical analysis revealed higher CDC20 protein expression levels
      in PDAC tissue than in normal pancreas tissue, and high CDC20 expression was
      associated with poor differentiation (P = 0.020) and a significantly lower 5-year
      recurrence-free survival rate (P = 0.039); we also found a trend toward a shorter
      overall survival duration. CONCLUSIONS: Aberrant CDC20 expression may play an
      important role in PDAC tumorigenesis and progression and may thus be useful as a
      marker of disease progression and prognosis and as a therapeutic target.

PMID- 22475565
TI  - Integrin-mediated adhesion of human mesenchymal stem cells to extracellular
      matrix proteins adsorbed to polymer surfaces.
AB  - In vitro, degradable aliphatic polyesters are widely used as cell carriers for
      bone tissue engineering, despite their lack of biological cues. Their biological
      active surface is rather determined by an adsorbed layer of proteins from the
      surrounding media. Initial cell fate, including adhesion and proliferation, which
      are key properties for efficient cell carriers, is determined by the adsorbed
      layer of proteins. Herein we have investigated the ability of human bone marrow
      derived stem cells (hBMSC) to adhere to extracellular matrix (ECM) proteins,
      including fibronectin and vitronectin which are present in plasma and serum.
      hBMSC expressed integrins for collagens, laminins, fibronectin and vitronectin.
      Accordingly, hBMSC strongly adhered to these purified ECM proteins by using the
      corresponding integrins. Although purified fibronectin and vitronectin adsorbed
      to aliphatic polyesters to a lower extent than to cell culture polystyrene, these
      low levels were sufficient to mediate adhesion of hBMSC. It was found that plasma
      and serum-coated polystyrene adsorbed significant levels of both fibronectin and
      vitronectin, and fibronectin was identified as the major adhesive component of
      plasma for hBMSC; however, aliphatic polyesters adsorbed minimal levels of
      fibronectin under similar conditions resulting in impaired cell adhesion.
      Altogether, the results suggest that the efficiency of aliphatic polyesters cell
      carriers could be improved by increasing their ability to adsorb fibronectin.

PMID- 22475566
TI  - Improving comfort of shoe sole through experiments based on CAD-FEM modeling.
AB  - It was reported that next to style, comfort is the second key aspect in
      purchasing footwear. One of the most important components of footwear is the shoe
      sole, whose design is based on many factors such as foot shape/size, perceived
      comfort and materials. The present paper focuses on the parametric analysis of a
      shoe sole to improve the perceived comfort. The sensitivity of geometric and
      material design factors on comfort degree was investigated by combining real
      experimental tests and CAD-FEM simulations. The correlation between perceived
      comfort and physical responses, such as plantar pressures, was estimated by
      conducting real tests. Four different conditions were analyzed: subjects wearing
      three commercially available shoes and in a barefoot condition. For each
      condition, subjects expressed their perceived comfort score. By adopting plantar
      sensors, the plantar pressures were also monitored. Once given such a
      correlation, a parametric FEM model of the footwear was developed. In order to
      better simulate contact at the plantar surface, a detailed FEM model of the foot
      was also generated from CT scan images. Lastly, a fractional factorial design
      array was applied to study the sensitivity of different sets of design factors on
      comfort degree. The findings of this research showed that the sole thickness and
      its material highly influence perceived comfort. In particular, softer materials
      and thicker soles contribute to increasing the degree of comfort.

PMID- 22475567
TI  - The development and psychometric testing of East Asian Acculturation Scale among
      Asian immigrant women in Taiwan.
AB  - OBJECTIVE: This is a report of development and psychometric testing of the East
      Asian Acculturation Measure-Chinese version (EAAM-C) scale. DESIGN: An instrument
      validation design with a cross-sectional survey was conducted. The process was
      carried in two phases. In Phase 1, Barry's East Asian Acculturation Measure was
      translated and back translated to evaluate its content, face validity, and
      feasibility validity. In Phase 2, the 16-item EAAM-C was pilot-tested among 485
      female immigrants for test-retest reliability, internal consistency,
      theoretically-supported construct validity and concurrent validity. RESULTS: The
      pilot work and the survey results indicated the tools possessed adequate content
      and face validity. The Cronbach's Alphas for the EAAM-C was 0.72, and 0.76-0.79
      for its subscales, and the correlation of test-retest reliability (at 3 weeks)
      was 0.75. After dropping one item, four theoretically-supported factors which
      explained 61.82% of the variance were abstracted using exploratory factor
      analysis: assimilation, integration, separation, and marginalization. Based on
      the underlying four-factor theoretical structures of the EAAM, the confirmatory
      factor analysis of the EAAM-C was further examined. The analysis revealed that
      the four-factor model was an acceptable fit for the data which demonstrated
      adequate finding in its construct validity. These factors were inter-correlated,
      and showed statistically significant correlation with the Chinese Health
      Questionnaire, indicating adequate concurrent validity. CONCLUSIONS: The scale
      shows acceptable validity and consistency, and suggests that immigrant
      acculturation is a complex construct. This quick evaluation instrument can be
      applied to assess clients' acculturation and in further developing certain
      interventions to improve their health.

PMID- 22475568
TI  - Behind the mask: Determinants of nurse's adherence to facial protective
      equipment.
AB  - BACKGROUND: As the predominant occupation in the health sector and as the health
      worker with the most patient interaction, nurses are at high risk for
      occupational transmission of communicable respiratory illness. The use of facial
      protective equipment (FPE) is an important strategy to prevent occupational
      transmission. METHODS: A 2-phased study was conducted to examine nurse's
      adherence to recommended use of FPE. Phase 1 was a cross-sectional survey of
      nurses in selected units of 6 acute care hospitals in Toronto, Canada. Phase 2
      was a direct observational study of critical care nurses. RESULTS: Of the 1,074
      nurses who completed surveys (82% response rate), 44% reported adherence to
      recommended use of FPE. Multivariable analysis revealed 6 predictors of
      adherence: unit type, frequency of equipment use, equipment availability,
      training, organizational support, and communication. Following the survey, 100
      observations in 14 intensive care units were conducted that revealed a 44%
      competence rate with proper use of N95 respirators and knowledge as a significant
      predictor of competence. CONCLUSION: Whereas increasing knowledge should enhance
      competence, strategies to improve adherence to recommended use of FPE in a busy
      and complex health care setting should focus on ready availability of equipment,
      training and fit testing, organizational support for worker health and safety,
      and good communication practices.

PMID- 22475569
TI  - Polymerase chain reaction testing for Clostridium difficile.

PMID- 22475570
TI  - Predictors of stethoscope disinfection among pediatric health care providers.
AB  - BACKGROUND: Stethoscopes are contaminated with bacteria, but predictors of
      stethoscope disinfection frequency are unknown. We sought to describe health care
      provider stethoscope disinfection attitudes and practices and determine
      predictors of frequent disinfection. METHODS: We used an anonymous online survey
      of nurses, nurse practitioners, and physicians at a pediatric hospital. We
      assessed frequency and methods of disinfection, perceptions of contamination, and
      barriers to disinfection. Multivariate logistic regression models were used to
      identify independent predictors of disinfecting after every use. RESULTS: One
      thousand four hundred one respondents completed the survey: 76% believed that
      infection transmission occurs via stethoscopes, but only 24% reported
      disinfecting after every use. In multivariate analyses, belief that infection
      transmission occurs via stethoscopes significantly increased the odds of
      disinfection after every use (odds ratio [OR], 2.06 [95% confidence interval
      (CI): 1.38-3.06]). The odds of disinfection after every use were significantly
      decreased in those who perceived the following barriers: lack of time (OR, 0.31
      [95% CI: 0.18-0.54]), lack of access to disinfection material (OR, 0.41 [95% CI:
      0.29-0.57]), or lack of visual reminders to disinfect (OR, 0.22 [95% CI: 0.14
      0.34]). CONCLUSION: Only a minority of pediatric health care providers reported
      disinfecting their stethoscopes after every use. Increasing access to
      disinfection materials and visual reminders in health care facilities may improve
      stethoscope disinfection practices.

PMID- 22475571
TI  - Immune dynamics following infection of avian macrophages and epithelial cells
      with typhoidal and non-typhoidal Salmonella enterica serovars; bacterial invasion
      and persistence, nitric oxide and oxygen production, differential host gene
      expression, NF-kappaB signalling and cell cytotoxicity.
AB  - Poultry-derived food is a common source of infection of human with the non-host
      adapted salmonellae while fowl typhoid and pullorum disease are serious diseases
      in poultry. Development of novel immune-based control strategies against
      Salmonella infection necessitates a better understanding of the host-pathogen
      interactions at the cellular level. Intestinal epithelial cells are the first
      line of defence against enteric infections and the role of macrophages is crucial
      in Salmonella infection and pathogenesis. While gene expression following
      Salmonella infection has been investigated, a comparison between different
      serovars has not been, as yet, extensively studied in poultry. In this study,
      chicken macrophage-like cells (HD11) and chick kidney epithelial cells (CKC) were
      used to study and compare the immune responses and mechanisms that develop after
      infection with different Salmonella serotypes. Salmonella serovars Typhimurium,
      Enteritidis, Hadar and Infantis showed a greater level of invasion and/or uptake
      characters when compared with S. Pullorum or S. Gallinarum. Nitrate and reactive
      oxygen species were greater in Salmonella-infected HD11 cells with the expression
      of iNOS and nuclear factor-kappaB by chicken macrophages infected with both
      systemic and broad host range serovars. HD11 cells revealed higher mRNA gene
      expression for CXCLi2, IL-6 and iNOS genes in response to S. Enteritidis
      infection when compared to S. Pullorum-infected cells. S. Typhimurium- and S.
      Hadar-infected HD11 showed higher gene expression for CXCLi2 versus S. Pullorum
      infected cells. Higher mRNA gene expression levels of pro-inflammatory cytokine
      IL-6, chemokines CXCLi1 and CXCLi2 and iNOS genes were detected in S. Typhimurium
      and S. Enteritidis-infected CKC followed by S. Hadar and S. Infantis while no
      significant changes were observed in S. Pullorum or S. Gallinarum-infected CKC.

PMID- 22475572
TI  - Canonical Wnt/beta-catenin signaling in epicardial fibrosis of failed pediatric
      heart allografts with diastolic dysfunction.
AB  - BACKGROUND: Failed pediatric heart allografts with diastolic dysfunction exhibit
      severe epicardial fibrosis. The molecular mechanism underlying this process is
      poorly understood. Canonical Wnt/beta-catenin signaling plays an important role
      in epithelial-mesenchymal transition and is implicated in fibrosing diseases. In
      this study, we tested the hypothesis that canonical Wnt/beta-catenin signaling is
      activated in epicardial fibrosis of end-stage dysfunctional pediatric allografts.
      METHODS: Fourteen explanted heart grafts of 12 patients who had undergone 14
      heart transplantations were used for immunohistochemical staining of beta-catenin
      and its nuclear binding partners, T-cell factor/lymphoid enhancer factor family
      transcriptional factors. Fourteen age-matched native hearts from patients who had
      undergone first heart transplantation without evidence of epicardial fibrosis
      were used as controls. RESULTS AND CONCLUSIONS: Epicardial fibroblasts from
      explanted allografts demonstrated nuclear accumulation of beta-catenin. These
      cells also showed nuclear positivity for T-cell factor 4. No T-cell factor 3
      expression was present in the epicardium. T-cell factor 1 and lymphoid enhancer
      factor 1 were observed in lymphocytes, but not in other cell types of the
      epicardium. These findings suggest an association between canonical Wnt/beta
      catenin signaling and epicardial fibrosis of failed pediatric heart allografts.
      Should activation of this pathway be shown to be causal to epicardial fibrosis in
      this setting, then inhibition of this pathway may help to prevent this
      devastating process.

PMID- 22475573
TI  - Modeling of simultaneous denitrification--anaerobic digestion--organic matter
      aerobic oxidation and nitrification in an anoxic-anaerobic-aerobic compact filter
      reactor.
AB  - A mathematical model was developed for a compact anoxic-anaerobic-aerobic filter
      reactor with liquid recirculation for the treatment of fishing effluents. The
      model includes denitrification, anaerobic digestion, aerobic carbon oxidation and
      nitrification steps, as well as an evaluation of the liquid gas mass transfer and
      pH. The model was calibrated using one experimental condition at a recycling
      ratio (R)=10, and was validated with R equal to 2 and 0, with an organic
      concentration of 554+/-24 mg TOCL(-1), salinity of 24 g L(-1) and hydraulic
      retention time (HRT) of 2 d. Carbon total removal is higher than 98%, while
      maximum nitrogen removal is 62% using total nitrification in the aerobic zone,
      due to a higher quantity of NO(x) produced which were recirculated to the anoxic
      zone. In the aerobic zone, simultaneous nitrification and denitrification
      processes occur, because the diffusion limitations cause a low oxygen penetration
      in the biofilm. In the anoxic-anaerobic zone, denitrification or methanogenesis
      inhibition by DO (caused by the recycled oxygen) is not observed.

PMID- 22475574
TI  - How dieting makes some fatter: from a perspective of human body composition
      autoregulation.
AB  - Dieting makes you fat - the title of a book published in 1983 - embodies the
      notion that dieting to control body weight predisposes the individual to acquire
      even more body fat. While this notion is controversial, its debate underscores
      the large gap that exists in our understanding of basic physiological laws that
      govern the regulation of human body composition. A striking example is the key
      role attributed to adipokines as feedback signals between adipose tissue
      depletion and compensatory increases in food intake. Yet, the relative importance
      of fat depletion per se as a determinant of post-dieting hyperphagia is unknown.
      On the other hand, the question of whether the depletion of lean tissues can
      provide feedback signals on the hunger-appetite drive is rarely invoked, despite
      evidence that food intake during growth is dominated by the impetus for lean
      tissue deposition, amidst proposals for the existence of protein-static
      mechanisms for the regulation of growth and maintenance of lean body mass. In
      fact, a feedback loop between fat depletion and food intake cannot explain why
      human subjects recovering from starvation continue to overeat well after body fat
      has been restored to pre-starvation values, thereby contributing to 'fat
      overshooting'. In addressing the plausibility and mechanistic basis by which
      dieting may predispose to increased fatness, this paper integrates the results
      derived from re-analysis of classic longitudinal studies of human starvation and
      refeeding. These suggest that feedback signals from both fat and lean tissues
      contribute to recovering body weight through effects on energy intake and
      thermogenesis, and that a faster rate of fat recovery relative to lean tissue
      recovery is a central outcome of body composition autoregulation that drives fat
      overshooting. A main implication of these findings is that the risk of becoming
      fatter in response to dieting is greater in lean than in obese individuals.

PMID- 22475575
TI  - Genetic evaluation of mastitis liability and recovery through longitudinal
      analysis of transition probabilities.
AB  - BACKGROUND: Many methods for the genetic analysis of mastitis use a cross
      sectional approach, which omits information on, e.g., repeated mastitis cases
      during lactation, somatic cell count fluctuations, and recovery process.
      Acknowledging the dynamic behavior of mastitis during lactation and taking into
      account that there is more than one binary response variable to consider, can
      enhance the genetic evaluation of mastitis. METHODS: Genetic evaluation of
      mastitis was carried out by modeling the dynamic nature of somatic cell count
      (SCC) within the lactation. The SCC patterns were captured by modeling transition
      probabilities between assumed states of mastitis and non-mastitis. A widely
      dispersed SCC pattern generates high transition probabilities between states and
      vice versa. This method can model transitions to and from states of infection
      simultaneously, i.e. both the mastitis liability and the recovery process are
      considered. A multilevel discrete time survival model was applied to estimate
      breeding values on simulated data with different dataset sizes, mastitis
      frequencies, and genetic correlations. RESULTS: Correlations between estimated
      and simulated breeding values showed that the estimated accuracies for mastitis
      liability were similar to those from previously tested methods that used data of
      confirmed mastitis cases, while our results were based on SCC as an indicator of
      mastitis. In addition, unlike the other methods, our method also generates
      breeding values for the recovery process. CONCLUSIONS: The developed method
      provides an effective tool for the genetic evaluation of mastitis when
      considering the whole disease course and will contribute to improving the genetic
      evaluation of udder health.

PMID- 22475576
TI  - [Two cases of autoimmune encephalitis with antibodies to N-methyl-D-aspartate
      receptor in intensive care].
AB  - We report here two cases of autoimmune encephalitis associated with antibodies
      against the N-methyl-D-aspartate receptor. The primary cause was an ovarian
      teratoma in one case. The outcomes were good. The first case was a late
      diagnosis, despite a typical clinical presentation. The clinical presentation of
      this disease remains unknown, especially in the intensive care unit. The
      treatment was recently codified and transformed the prognosis of this
      encephalitis. The second case was early treated in the course of the disease, due
      to the experience related to the previous case. In case of unexplained acute or
      subacute encephalitis or psychiatric-like disorders without prior medical
      history, the determination of the level of expression of antibodies against the N
      methyl-D-aspartate receptors and other antineuroreceptors antibodies can help to
      identify this diagnosis. The initial picture of the disease, its variability and
      the unawareness of the recent reports on this encephalitis may lead to a wrong
      diagnosis and inappropriate management.

PMID- 22475577
TI  - Working memory training: improving intelligence--changing brain activity.
AB  - The main objectives of the study were: to investigate whether training on working
      memory (WM) could improve fluid intelligence, and to investigate the effects WM
      training had on neuroelectric (electroencephalography - EEG) and hemodynamic
      (near-infrared spectroscopy - NIRS) patterns of brain activity. In a parallel
      group experimental design, respondents of the working memory group after 30 h of
      training significantly increased performance on all tests of fluid intelligence.
      By contrast, respondents of the active control group (participating in a 30-h
      communication training course) showed no improvements in performance. The
      influence of WM training on patterns of neuroelectric brain activity was most
      pronounced in the theta and alpha bands. Theta and lower-1 alpha band
      synchronization was accompanied by increased lower-2 and upper alpha
      desynchronization. The hemodynamic patterns of brain activity after the training
      changed from higher right hemispheric activation to a balanced activity of both
      frontal areas. The neuroelectric as well as hemodynamic patterns of brain
      activity suggest that the training influenced WM maintenance functions as well as
      processes directed by the central executive. The changes in upper alpha band
      desynchronization could further indicate that processes related to long term
      memory were also influenced.

PMID- 22475578
TI  - Spatial analysis after perinatal stroke: patterns of neglect and exploration in
      extra-personal space.
AB  - This study was conducted to determine whether school-aged children who had
      experienced a perinatal stroke demonstrate evidence of persistent spatial
      neglect, and if such neglect was specific to the visual domain or was more
      generalized. Two studies were carried out. In the first, 38 children with either
      left hemisphere (LH) or right hemisphere (RH) damage and 50 age-matched controls
      were given visual cancellation tasks varying in two factors: target stimuli and
      stimulus array. In the second study, tactile neglect was evaluated in 41 children
      with LH or RH damage and 72 age-matched controls using a blindfolded manual
      exploration task. On the visual cancellation task, LH subjects omitted more
      target stimuli on the right, but also on the left, compared with controls.
      Children with RH lesions also produced a larger number of omissions on both the
      left and right sides than controls, but with poorer performance on the left. On
      the manual exploration task, LH children required significantly longer times to
      locate the target on both sides of the board than did controls. RH children had
      significantly prolonged search times on the left side, but not on the right,
      compared with controls. In both tasks, LH subjects employed unsystematic search
      strategies more often than both control and RH children. The search strategy of
      RH children also tended to be erratic when compared to controls, but only in the
      random arrays of the visual cancellation tasks; structure of the target stimuli
      improved their organization. These results demonstrate that children with early
      LH brain damage display bilateral difficulties in visual and tactile modalities;
      a pattern that is in contrast to that seen in adults with LH damage. This may
      result from disorganized search strategies or other subtle spatial or attentional
      deficits. Results of performance of RH children suggests the presence of
      contralateral neglect in both the visual and tactile modalities; a finding that
      is similar to the neglect in adult stroke patients with RH lesions. The fact that
      deficits in spatial attention and organizational strategies are present after
      very early focal damage to either the LH or the RH broadens our understanding of
      the differences in functional lateralization between the immature and mature
      brain. These results also add to evidence for limitations to plasticity in the
      developing brain. Our findings may have therapeutic and rehabilitative
      implications for the management of children with early focal brain lesions.

PMID- 22475579
TI  - Hemispheric asymmetry in the efficiency of attentional networks.
AB  - Despite the fact that hemispheric asymmetry of attention has been widely studied,
      a clear picture of this complex phenomenon is still lacking. The aim of the
      present study was to provide an efficient and reliable measurement of potential
      hemispheric asymmetries of three attentional networks, i.e. alerting, orienting
      and executive attention. Participants (N=125) were tested with the Lateralized
      Attention Network Test (LANT) that allowed us to investigate the efficiency of
      the networks in both visual fields (VF). We found a LVF advantage when a target
      occurred in an unattended location, which seems to reflect right hemisphere
      superiority in control of the reorienting of attention. Furthermore, a LVF
      advantage in conflict resolution was observed, which may indicate hemispheric
      asymmetry of the executive network. No VF effect for alerting was found. The
      results, consistent with the common notion of general right hemisphere dominance
      for attention, provide a more detailed account of hemispheric asymmetries of the
      attentional networks than previous studies using the LANT task.

PMID- 22475580
TI  - Spatiotemporal air pollution exposure assessment for a Canadian population-based
      lung cancer case-control study.
AB  - BACKGROUND: Few epidemiological studies of air pollution have used residential
      histories to develop long-term retrospective exposure estimates for multiple
      ambient air pollutants and vehicle and industrial emissions. We present such an
      exposure assessment for a Canadian population-based lung cancer case-control
      study of 8353 individuals using self-reported residential histories from 1975 to
      1994. We also examine the implications of disregarding and/or improperly
      accounting for residential mobility in long-term exposure assessments. METHODS:
      National spatial surfaces of ambient air pollution were compiled from recent
      satellite-based estimates (for PM2.5 and NO2) and a chemical transport model (for
      O3). The surfaces were adjusted with historical annual air pollution monitoring
      data, using either spatiotemporal interpolation or linear regression. Model
      evaluation was conducted using an independent ten percent subset of monitoring
      data per year. Proximity to major roads, incorporating a temporal weighting
      factor based on Canadian mobile-source emission estimates, was used to estimate
      exposure to vehicle emissions. A comprehensive inventory of geocoded industries
      was used to estimate proximity to major and minor industrial emissions. RESULTS:
      Calibration of the national PM2.5 surface using annual spatiotemporal
      interpolation predicted historical PM2.5 measurement data best (R2 = 0.51), while
      linear regression incorporating the national surfaces, a time-trend and
      population density best predicted historical concentrations of NO2 (R2 = 0.38)
      and O3 (R2 = 0.56). Applying the models to study participants residential
      histories between 1975 and 1994 resulted in mean PM2.5, NO2 and O3 exposures of
      11.3 MUg/m3 (SD = 2.6), 17.7 ppb (4.1), and 26.4 ppb (3.4) respectively. On
      average, individuals lived within 300 m of a highway for 2.9 years (15% of
      exposure-years) and within 3 km of a major industrial emitter for 6.4 years (32%
      of exposure-years). Approximately 50% of individuals were classified into a
      different PM2.5, NO2 and O3 exposure quintile when using study entry postal codes
      and spatial pollution surfaces, in comparison to exposures derived from
      residential histories and spatiotemporal air pollution models. Recall bias was
      also present for self-reported residential histories prior to 1975, with cases
      recalling older residences more often than controls. CONCLUSIONS: We demonstrate
      a flexible exposure assessment approach for estimating historical air pollution
      concentrations over large geographical areas and time-periods. In addition, we
      highlight the importance of including residential histories in long-term exposure
      assessments. For submission to: Environmental Health.

PMID- 22475581
TI  - Interaction of virions with membrane glycolipids.
AB  - Cellular membranes contain various lipids including glycolipids (GLs). The
      hydrophilic head groups of GLs extend from the membrane into the aqueous
      environment outside the cell where they act as recognition sites for specific
      interactions. The first steps of interaction of virions with cells often include
      contacts with GLs. To clarify the details of such contacts, we have used the
      total internal reflection fluorescence microscopy to explore the interaction of
      individual unlabelled virus-like particles (or, more specifically, norovirus
      protein capsids), which are firmly bound to a lipid bilayer, and fluorescent
      vesicles containing glycosphingolipids (these lipids form a subclass of GLs). The
      corresponding binding kinetics were earlier found to be kinetically limited,
      while the detachment kinetics were logarithmic over a wide range of time. Here,
      the detachment rate is observed to dramatically decrease with increasing
      concentration of glycosphingolipids from 1% to 8%. This effect has been
      analytically explained by using a generic model describing the statistics of
      bonds in the contact area between a virion and a lipid membrane. Among other
      factors, the model takes the formation of GL domains into account. Our analysis
      indicates that in the system under consideration, such domains, if present, have
      a characteristic size smaller than the contact area between the vesicle and the
      virus-like particle.

PMID- 22475582
TI  - Development of a visual loop-mediated isothermal amplification method for rapid
      detection of the bacterial pathogen Pseudomonas putida of the large yellow
      croaker (Pseudosciaena crocea).
AB  - In recent years, the large yellow croaker (Pseudosciaena crocea), an important
      marine fish farmed in the coastal areas of Zhejiang province, east China, has
      become severely endangered as a result of the bacterial pathogen Pseudomonas
      putida. This paper reports the development of a visual loop-mediated isothermal
      amplification (LAMP) assay for rapid detection of the pathogen. Four primers, F3,
      B3, FIP and BIP, were designed on the basis of DNA sequence of the rpoN gene of
      P. putida. After optimization of the reaction conditions, the detection limit of
      LAMP assay was 4.8cfu per reaction, 10-fold higher than that of conventional PCR.
      The assay showed high specificity to discriminate all P. putida isolates from
      nine other Gram-negative bacteria. The assay also successfully detected the
      pathogen DNA in the tissues of infected fish. For visual LAMP without cross
      contamination, SYBR Green I was embedded in a microcrystalline wax capsule and
      preset in the reaction tubes; after the reaction the wax was melted at 85 degrees
      C to release the dye and allow intercalation with the amplicons. The simple,
      highly sensitive, highly specific and cost-effective characteristics of visual
      LAMP may encourage its application in the rapid diagnosis of this pathogen.

PMID- 22475583
TI  - Mediation-moderation analysis of problematic alcohol use: the roles of urgency,
      drinking motives, and risk/benefit perception.
AB  - OBJECTIVE: The goal of the current study is to examine how urgency, drinking
      motives, and risk/benefit perception concurrently influence problematic alcohol
      consumption in young adults. METHOD: Participants were 281 young adults enrolled
      in large, public US mid-western university. The mean age of the sample was 19.81
      (SD=1.82) and 79.7% of the sample was female and 84.7% of the sample was
      Caucasian. RESULTS: A series of moderated-mediation analyses indicated the
      following: The relationship between negative urgency and alcohol use was mediated
      through coping motives, and this relationship between coping motives and alcohol
      use was moderated by benefit perception. The relationship between positive
      urgency and alcohol use was mediated through enhancement motives, and this
      relationship between enhancement motives and alcohol use was moderated by benefit
      perception. CONCLUSIONS: This study suggests that modifying perceptions about the
      benefits of alcohol and drinking motives could be viable prevention and/or
      treatment strategy in this population, especially among those who exhibit urgent
      behaviors.

PMID- 22475584
TI  - Student and school characteristics associated with use of nicotine replacement
      therapy: a multilevel analysis among Canadian youth.
AB  - BACKGROUND: Research indicates that it is common for youths to use nicotine
      replacement therapy (NRT) despite limited empirical evidence for its
      effectiveness within this population. Since very little is known about the
      characteristics associated with NRT use by youth, the current study examined the
      association between ever and current use of NRT as a function of student
      characteristics and the characteristics of the schools they attend. METHODS: This
      study used nationally representative student-level data from 29,296 grade 9 to 12
      students who participated in the 2008-2009 Canadian Youth Smoking Survey (YSS).
      School-level data on the built environment surrounding schools were provided by
      DMTI-Spatial, and data on school location were provided by the Canadian Census.
      Two multilevel logistic regression models were used to predict ever use of NRT
      and current use of NRT as a function of student and school characteristics among
      current smokers. RESULTS: Overall, 21.1% of youth smokers in Canada had ever used
      NRT and 5.1% were currently using NRT. Odds of ever and current NRT use were
      highest among daily smokers and boys, while youths who had made multiple quit
      attempts or participated in a quit and win contest were more likely to be ever
      NRT users. Attending a school located within an urban area increased youths' odds
      of ever and current NRT use, whereas higher density of pharmacies surrounding a
      school was inversely associated with current NRT use. CONCLUSIONS:
      Characteristics of students and the schools they attend were associated with the
      likelihood of youth smokers using NRT. Significant between-school differences in
      NRT use exist, however further research is needed to identify which school
      characteristics account for these differences and understand how youth are
      accessing NRT.

PMID- 22475585
TI  - [Breastfeeding: opinion and knowledge of pharmacists. A study in a semi-urban
      territory].
AB  - BACKGROUND: Because of the French delay regarding breastfeeding compared to other
      Europeans countries, its promotion was one of the 9 specific nutritional goals of
      the 2001, 2006, and 2011 National Nutritional Health Program. The objective of
      this study was to establish the opinion and knowledge of pharmacists from a
      selected semi-urban territory of the Lille metropolitan area on breastfeeding.
      METHOD: The 33 pharmacies around the city of Villeneuve-d'Ascq were contacted.
      First, the goal and the principles of the study were presented to the pharmacists
      and they were invited to participate in a survey. This survey was divided into 6
      topics with 26 questions. The topics were: advice on breastfeeding, pain and
      inflammation during breastfeeding, use of a breast pump, preservation and
      reheating of breast milk, breastfeeding and medication, breastfeeding and
      contraception, and breastfeeding promotion. The survey also evaluated their
      willingness to promote breastfeeding and the assistance needed for undertaking
      this promotion. By counting the right answers from 13 of the 26 questions, a
      global grade was calculated reflecting the knowledge of the participants. The
      maximum grade was 20 because many questions had several correct answers. RESULTS:
      Twenty-nine pharmacies agreed to participate (participation rate, 88%). The mean
      grade was 13.4 (95% CI: 12.7-14.0). Professional and personal experience had no
      influence on the grades. In the opinion of the pharmacists, the 3 topics most
      frequently raised by women were cracked nipples, mastitis, and painful breast
      (quoted by 83% of the pharmacists), the infant formula to use as a complete or
      partial substitute for breastfeeding (66%), and breastfeeding and medication
      (59%). Fifty-five percent of the participants were aware of the WHO
      recommendations on exclusive breastfeeding up to 6 months of age. The desire to
      promote breastfeeding was strong (68%). Thus, all pharmacists favored the
      distribution of a leaflet giving information on breastfeeding. CONCLUSION: This
      study shows a strong desire to promote breastfeeding among the pharmacists
      surveyed. It allows focusing on the themes that could be the target for
      continuing education, based on mothers' needs.

PMID- 22475587
TI  - [Recurrence of immune thrombocytopenic purpura].

PMID- 22475588
TI  - Effect of sampling size on the determination of accurate pesticide residue levels
      in Japanese agricultural commodities.
AB  - The uncertainty in pesticide residue levels (UPRL) associated with sampling size
      was estimated using individual acetamiprid and cypermethrin residue data from
      preharvested apple, broccoli, cabbage, grape, and sweet pepper samples. The
      relative standard deviation from the mean of each sampling size (n = 2(x), where
      x = 1-6) of randomly selected samples was defined as the UPRL for each sampling
      size. The estimated UPRLs, which were calculated on the basis of the regulatory
      sampling size recommended by the OECD Guidelines on Crop Field Trials (weights
      from 1 to 5 kg, and commodity unit numbers from 12 to 24), ranged from 2.1% for
      cypermethrin in sweet peppers to 14.6% for cypermethrin in cabbage samples. The
      percentages of commodity exceeding the maximum residue limits (MRLs) specified by
      the Japanese Food Sanitation Law may be predicted from the equation derived from
      this study, which was based on samples of various size ranges with mean residue
      levels below the MRL. The estimated UPRLs have confirmed that sufficient sampling
      weight and numbers are required for analysis and/or re-examination of subsamples
      to provide accurate values of pesticide residue levels for the enforcement of
      MRLs. The equation derived from the present study would aid the estimation of
      more accurate residue levels even from small sampling sizes.

PMID- 22475589
TI  - Building a better physician--the case for the new MCAT.

PMID- 22475590
TI  - Removing legal barriers to high-quality care for HIV-infected patients.

PMID- 22475591
TI  - HIV and aging--preparing for the challenges ahead.

PMID- 22475592
TI  - Immune-correlates analysis of an HIV-1 vaccine efficacy trial.
AB  - BACKGROUND: In the RV144 trial, the estimated efficacy of a vaccine regimen
      against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a
      case-control analysis to identify antibody and cellular immune correlates of
      infection risk. METHODS: In pilot studies conducted with RV144 blood samples, 17
      antibody or cellular assays met prespecified criteria, of which 6 were chosen for
      primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody
      responses in the modulation of infection risk. Assays were performed on samples
      from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2
      weeks after final immunization, to evaluate whether immune-response variables
      predicted HIV-1 infection through 42 months of follow-up. RESULTS: Of six primary
      variables, two correlated significantly with infection risk: the binding of IgG
      antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env)
      correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57
      per 1-SD increase; P=0.02; q=0.08), and the binding of plasma IgA antibodies to
      Env correlated directly with the rate of infection (estimated odds ratio, 1.54
      per 1-SD increase; P=0.03; q=0.08). Neither low levels of V1V2 antibodies nor
      high levels of Env-specific IgA antibodies were associated with higher rates of
      infection than were found in the placebo group. Secondary analyses suggested that
      Env-specific IgA antibodies may mitigate the effects of potentially protective
      antibodies. CONCLUSIONS: This immune-correlates study generated the hypotheses
      that V1V2 antibodies may have contributed to protection against HIV-1 infection,
      whereas high levels of Env-specific IgA antibodies may have mitigated the effects
      of protective antibodies. Vaccines that are designed to induce higher levels of
      V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced
      by the RV144 vaccine may have improved efficacy against HIV-1 infection.

PMID- 22475593
TI  - Pyronaridine-artesunate versus mefloquine plus artesunate for malaria.
AB  - BACKGROUND: Pyronaridine-artesunate is an artemisinin-based combination therapy
      under evaluation for the treatment of Plasmodium falciparum and P. vivax malaria.
      METHODS: We conducted a phase 3, open-label, multicenter, noninferiority trial
      that included 1271 patients between 3 and 60 years of age from Asia (81.3%) or
      Africa (18.7%) with microscopically confirmed, uncomplicated P. falciparum
      malaria. Patients underwent randomization for treatment with a fixed-dose
      combination of 180 mg of pyronaridine and 60 mg of artesunate or with 250 mg of
      mefloquine plus 100 mg of artesunate. Doses were calculated according to body
      weight and administered once daily for 3 days. RESULTS: Pyronaridine-artesunate
      was noninferior to mefloquine plus artesunate for the primary outcome: adequate
      clinical and parasitologic response in the per-protocol population on day 28,
      corrected for reinfection with the use of polymerase-chain-reaction (PCR)
      genotyping. For this outcome, efficacy in the group receiving pyronaridine
      artesunate was 99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3 to
      99.7) and that in the group receiving mefloquine plus artesunate was 97.8% (360
      of 368 patients; 95% CI, 95.8 to 99.1), with a treatment difference of 1.4
      percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat
      population, efficacy on day 42 in the group receiving pyronaridine-artesunate was
      83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that in the group receiving
      mefloquine plus artesunate was 83.9% (355 of 423 patients; 95% CI, 80.1 to 87.3).
      In Cambodia, where there were 211 study patients, the median parasite clearance
      time was prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours in
      other countries (P<0.001, on the basis of Kaplan-Meier estimates). Kaplan-Meier
      estimates of the recrudescence rate in the intention-to-treat population in
      Cambodia until day 42 were higher with pyronaridine-artesunate than with
      mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as
      calculated with the log-rank test), but similar for the other countries combined
      (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24).
      Elevated levels of aminotransferases were observed in those receiving
      pyronaridine-artesunate. Two patients receiving mefloquine plus artesunate had
      seizures. CONCLUSIONS: Fixed-dose pyronaridine-artesunate was efficacious in the
      treatment of uncomplicated P. falciparum malaria. In Cambodia, extended parasite
      clearance times were suggestive of in vivo resistance to artemisinin. (Funded by
      Shin Poong Pharmaceutical Company and the Medicines for Malaria Venture;
      ClinicalTrials.gov number, NCT00403260.).

PMID- 22475594
TI  - Suicide and cardiovascular death after a cancer diagnosis.
AB  - BACKGROUND: Receiving a diagnosis of cancer is a traumatic experience that may
      trigger immediate adverse health consequences beyond the effects of the disease
      or treatment. METHODS: Using Poisson and negative binomial regression models, we
      conducted a historical cohort study involving 6,073,240 Swedes to examine the
      associations between a cancer diagnosis and the immediate risk of suicide or
      death from cardiovascular causes from 1991 through 2006. To adjust for unmeasured
      confounders, we also performed a nested, self-matched case-crossover analysis
      among all patients with cancer who died from suicide or cardiovascular diseases
      in the cohort. RESULTS: As compared with cancer-free persons, the relative risk
      of suicide among patients receiving a cancer diagnosis was 12.6 (95% confidence
      interval [CI], 8.6 to 17.8) during the first week (29 patients; incidence rate,
      2.50 per 1000 person-years) and 3.1 (95% CI, 2.7 to 3.5) during the first year
      (260 patients; incidence rate, 0.60 per 1000 person-years). The relative risk of
      cardiovascular death after diagnosis was 5.6 (95% CI, 5.2 to 5.9) during the
      first week (1318 patients; incidence rate, 116.80 per 1000 person-years) and 3.3
      (95% CI, 3.1 to 3.4) during the first 4 weeks (2641 patients; incidence rate,
      65.81 per 1000 person-years). The risk elevations decreased rapidly during the
      first year after diagnosis. Increased risk was particularly prominent for cancers
      with a poor prognosis. The case-crossover analysis largely confirmed results from
      the main analysis. CONCLUSIONS: In this large cohort study, patients who had
      recently received a cancer diagnosis had increased risks of both suicide and
      death from cardiovascular causes, as compared with cancer-free persons. (Funded
      by the Swedish Council for Working Life and Social Research and others.).

PMID- 22475595
TI  - Clinical practice. Glycemic management of type 2 diabetes mellitus.

PMID- 22475596
TI  - What we don't see.

PMID- 22475597
TI  - Images in clinical medicine. Digital mucous cyst.

PMID- 22475598
TI  - Clinical problem-solving. Skin deep.

PMID- 22475599
TI  - The road to an effective HIV vaccine.

PMID- 22475600
TI  - Metabolic health and nuclear-receptor sensitivity.

PMID- 22475602
TI  - Pertuzumab plus trastuzumab in metastatic breast cancer.

PMID- 22475603
TI  - Pertuzumab plus trastuzumab in metastatic breast cancer.

PMID- 22475604
TI  - Pertuzumab plus trastuzumab in metastatic breast cancer.

PMID- 22475606
TI  - Subclinical atrial fibrillation and the risk of stroke.

PMID- 22475607
TI  - Subclinical atrial fibrillation and the risk of stroke.

PMID- 22475608
TI  - Subclinical atrial fibrillation and the risk of stroke.

PMID- 22475609
TI  - Subclinical atrial fibrillation and the risk of stroke.

PMID- 22475610
TI  - Subclinical atrial fibrillation and the risk of stroke.

PMID- 22475612
TI  - Low-dose interleukin-2 and HCV-induced vasculitis.

PMID- 22475613
TI  - Defense costs of medical malpractice claims.

PMID- 22475617
TI  - Images in clinical medicine. Left main coronary artery thrombosis.

PMID- 22475618
TI  - Hereditary motor neuron disease in a large Norwegian family with a "H46R"
      substitution in the superoxide dismutase 1 gene.
AB  - Mutant genes associated with Charcot Marie Tooth type 2, distal hereditary motor
      neuropathy and familial amyotrophic lateral sclerosis may cause overlapping
      clinical phenotypes. We performed whole genome linkage analysis, haplotype
      analysis, sequencing and detailed clinical and neurophysiological investigations
      in a large Norwegian kindred with a condition that clinically had been classified
      as Charcot Marie Tooth type 2. The mutation c.140A>G, p.His47Arg (alias
      p.His46Arg or H46R) in the superoxide dismutase 1 gene (SOD1) segregated with the
      disease. The patients present a hereditary motor neuropathy-like clinical picture
      and long survival (mean 29years). To our knowledge, this is the first extensive
      report describing a large non-Japanese kindred. The prognostic implications of
      the condition seen in this family have little in common with what is normally
      associated with sporadic amyotrophic lateral sclerosis and illustrates the
      complexity of the genetic etiology of lower motor neuron disease.

PMID- 22475619
TI  - Evaluating the mitochondrial function.

PMID- 22475620
TI  - Serum leptin and cognitive function in people with type 2 diabetes.
AB  - People with obesity and type 2 diabetes are at increased risk of cognitive
      impairment. We aimed to investigate the association of leptin with cognitive
      abilities in an elderly population with type 2 diabetes. We performed a cross
      sectional study of 1057 men and women aged 60-75 years with type 2 diabetes
      living in Lothian (Scotland). A cognitive battery was administered. Prior
      intelligence was estimated from vocabulary testing and adjustment for scores on
      this test was used to estimate lifetime cognitive change. Relationships between
      fasting morning leptin levels and cognitive ability and estimated cognitive
      change were tested. Higher leptin levels were associated with significantly
      poorer estimated overall cognitive decline, and poorer performance in 2 cognitive
      domains assessing mental flexibility and executive function, only amongst men (p
      < 0.05). High morning leptin levels in elderly men with type 2 diabetes are
      associated with estimated age-related cognitive change.

PMID- 22475621
TI  - Presenilin mediates neuroprotective functions of ephrinB and brain-derived
      neurotrophic factor and regulates ligand-induced internalization and metabolism
      of EphB2 and TrkB receptors.
AB  - Activation of EphB receptors by ephrinB (efnB) ligands on neuronal cell surface
      regulates important functions, including neurite outgrowth, axonal guidance, and
      synaptic plasticity. Here, we show that efnB rescues primary cortical neuronal
      cultures from necrotic cell death induced by glutamate excitotoxicity and that
      this function depends on EphB receptors. Importantly, the neuroprotective
      function of the efnB/EphB system depends on presenilin 1 (PS1), a protein that
      plays crucial roles in Alzheimer's disease (AD) neurodegeneration. Furthermore,
      absence of one PS1 allele results in significantly decreased neuroprotection,
      indicating that both PS1 alleles are necessary for full expression of the
      neuroprotective activity of the efnB/EphB system. We also show that the ability
      of brain-derived neurotrophic factor (BDNF) to protect neuronal cultures from
      glutamate-induced cell death depends on PS1. Neuroprotective functions of both
      efnB and BDNF, however, were independent of gamma-secretase activity. Absence of
      PS1 decreases cell surface expression of neuronal TrkB and EphB2 without
      affecting total cellular levels of the receptors. Furthermore, PS1-knockout
      neurons show defective ligand-dependent internalization and decreased ligand
      induced degradation of TrkB and Eph receptors. Our data show that PS1 mediates
      the neuroprotective activities of efnB and BDNF against excitotoxicity and
      regulates surface expression and ligand-induced metabolism of their cognate
      receptors. Together, our observations indicate that PS1 promotes neuronal
      survival by regulating neuroprotective functions of ligand-receptor systems.

PMID- 22475622
TI  - A variant of the neuronal amino acid transporter SLC6A15 is associated with ACTH
      and cortisol responses and cognitive performance in unipolar depression.
AB  - Major depressive disorder (MDD) is accompanied by both cognitive impairments and
      a hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system,
      resulting in an enhanced glucocorticoid secretion. Cortisol acts via
      mineralocorticoid and glucocorticoid receptors densely located in the
      hippocampus, a brain area that is important regarding cognitive functions and
      especially memory functions. Recently, a variant (rs1545843) affecting
      transcription of the human SLC6A15 gene has been associated with depression in a
      genome-wide association study. In an animal model, the neuronal amino acid
      transporter SLC6A15 was found to be decreased in stress-susceptible mice. Against
      the background of stress impacting on the activity of the HPA axis, we have
      investigated alterations of adrenocorticotropic hormone (ACTH) and cortisol
      secretion in the combined dexamethasone/corticotrophin-releasing hormone
      (Dex/CRH) test as well as memory and attention performance in a sample of 248
      patients with unipolar depression and 172 healthy control subjects genotyped for
      rs1545843. MDD patients carrying the depression-associated AA genotype showed
      enhanced maximum and area under the curve ACTH and cortisol answers (p = 0.03) as
      well as an impaired memory and impaired sustained attention performance (p =
      0.04) compared to carriers of at least one G allele. No effects of the SLC6A15
      variant were found in the healthy control group. Our findings argue for a role of
      the SLC6A15 gene in ACTH and cortisol secretion during the Dex/CRH test and
      furthermore in the occurrence of cognitive impairments in unipolar depression.

PMID- 22475623
TI  - The use of a reversible proteasome inhibitor in a model of Reduced-Size
      Orthotopic Liver transplantation in rats.
AB  - Ischemia/reperfusion injury (IRI), inherent in liver transplantation (LT), is the
      main cause of initial deficiencies and primary non-function of liver allografts.
      Living-related LT was developed to alleviate the mortality resulting from the
      scarcity of suitable deceased grafts. The main problem in using living-related LT
      for adults is graft size disparity. In this study we propose for the first time
      that the use of a proteasome inhibitor (Bortezomib) treatment could improve liver
      regeneration and reduce IRI after Reduced-Size Orthotopic Liver transplantation
      (ROLT). Rat liver grafts were reduced by removing the left lateral lobe and the
      two caudate lobes and preserved in UW or IGL-1 preservation solution for 1h liver
      and then subjected to ROLT with or without Bortezomib treatment. Our results show
      that Bortezomib reduces IRI after LT and is correlated with a reduction in
      mitochondrial damage, oxidative stress and endoplasmic reticulum stress.
      Furthermore, Bortezomib also increased liver regeneration after reduced-size LT
      and increased the expression of well-known ischemia/reperfusion protective
      proteins such as nitric oxide synthase, heme oxigenase 1 (HO-1) and Heat Shock
      Protein 70. Our results open new possibilities for the study of alternative
      therapeutic strategies aimed at reducing IRI and increasing liver regeneration
      after LT. It is hoped that the results of our study will contribute towards
      improving the understanding of the molecular processes involved in IRI and liver
      regeneration, and therefore help to improve the outcome of this type of LT in the
      future.

PMID- 22475624
TI  - IgM-monoclonal gammopathy neuropathy and tremor: a first epidemiologic case
      control study.
AB  - INTRODUCTION: Small case series suggest tremor occurs frequently in IgM
      monoclonal gammopathy of undetermined significance (IgM-MGUS) neuropathy.
      Epidemiologic study to confirm this association is lacking. Whether the
      neuropathy or another remote IgM-effect is causal remains unsettled. MATERIALS
      AND METHODS: An IgM-MGUS neuropathy case cohort (n = 207) was compared to age,
      gender, and neuropathy impairment score (NIS) matched, other-cause neuropathy
      controls (n = 414). Tremor details were extracted from structured neurologic
      evaluation. All patients underwent nerve conductions. RESULTS: Tremor occurrence
      was significantly higher in IgM-MGUS case cohort (29%) than in control cohort
      (9.2%) (p = 0.001). In IgM-MGUS cases, tremor was associated with worse NIS (p =
      0.025) and demyelinating nerve conductions (p = 0.020), but 11 of 60 (18%) IgM
      MGUS cases with tremor had axonal neuropathy. In other-cause neuropathy controls,
      tremor was associated with axonal nerve conductions (p = 0.03) but not with NIS
      severity (p = 0.57). Tremor occurrence associated with older age in controls, (p
      = 0.004) but not in IgM-MGUS cases (p = 0.272). Most IgM-MGUS tremor cases
      (49/60) had a postural-kinetic tremor, 8 had rest tremor, 3 had mixed rest
      action. Alternative causes of tremor was identified in 42% of IgM-MGUS cases, the
      most common type is inherited essential tremor 6/60 (p = 0.04). CONCLUSIONS: This
      first epidemiologic case-control study validates association between IgM-MGUS
      neuropathy and tremor. Among IgM-MGUS neuropathy cases, severity as well as type
      of neuropathy (demyelinating over axonal) correlated with tremor occurrence. IgM
      MGUS paraproteinemia may increase tremor expression in persons recognized with
      common other risk factors for tremor.

PMID- 22475625
TI  - alpha-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested
      decreased anxiety-like behavior and hyperlocomotion.
AB  - alpha-Synuclein (alpha-syn), the main component of Lewy bodies, was identified as
      a genetic risk factor for idiopathic Parkinson's disease (PD). As a model for PD,
      we generated human alpha-syn bacterial artificial chromosome transgenic mice (BAC
      tg mice) harboring the entire human alpha-syn gene and its gene expression
      regulatory regions. The alpha-syn BAC tg mice manifested decreased anxiety-like
      behaviors which may reflect non-motor symptoms of early PD, and they exhibited
      increased SERT expression that may be responsible for decreased anxiety-like
      behaviors. Our alpha-syn BAC tg mice could be a valuable tool to evaluate alpha
      syn gene dosage effects in vivo.

PMID- 22475626
TI  - Salmonella infects B cells by macropinocytosis and formation of spacious
      phagosomes but does not induce pyroptosis in favor of its survival.
AB  - We have previously reported that Salmonella infects B cells and survives within
      endosomal-lysosomal compartments. However, the mechanisms used by Salmonella to
      enter B cells remain unknown. In this study, we have shown that Salmonella
      induces its own entry by the induction of localized ruffling, macropinocytosis,
      and spacious phagosome formation. These events were associated with the
      rearrangement of actin and microtubule networks. The Salmonella pathogenesis
      island 1 (SPI-1) was necessary to invade B cells. In contrast to macrophages, B
      cells were highly resistant to cell death induced by Salmonella. These data
      demonstrate the ability of Salmonella to infect these non-professional phagocytic
      cells, where the bacterium can find an ideal intracellular niche to support
      persistence and the possible dissemination of infection.

PMID- 22475627
TI  - Nicotine alters the ectonucleotidases activities in lymphocytes: In vitro and in
      vivo studies.
AB  - The aim of the present study was to investigate the effects in vivo and in vitro
      of nicotine, an important immunosuppressive agent, on NTPDase and ADA activities
      in lymphocytes of adult rats. The following nicotine doses in vivo study were
      evaluated: 0.0, 0.25 and 1.0mg/kg/day injected subcutaneously in rats for 10days.
      The activity of the enzymes were significantly decreased with nicotine 0.25 and
      1mg/kg which inhibited ATP (22%, 54%), ADP (44%, 30%) hydrolysis and adenosine
      (43%, 34%) deamination, respectively. The expression of the protein NTPDase in
      rat lymphocytes was decreased to nicotine 1mg/kg and the lymphocytes count was
      decreased in both nicotine doses studied. The purine levels measured in serum of
      the rats treated with nicotine 0.25mg/kg significantly increased to ATP (39%),
      ADP (39%) and adenosine (303%). The nicotine exposure marker was determinate by
      level of cotinine level which significantly increased in rats treated with
      nicotine 0.25 (39%) and 1mg/kg (131%) when compared to rats that received only
      saline. The second set of study was in vitro assay which the ATP-ADP-adenosine
      hydrolysis were decreased by nicotine concentrations 1mM (0% - 0% - 16%,
      respectively), 5mM (42% - 32% - 74%, respectively), 10mM (80% - 27% - 80%,
      respectively) and 50mM (96% - 49% - 98%, respectively) when compared with the
      control group. We suggest that alterations in the activities of these enzymes may
      contribute to the understanding of the mechanisms involved in the suppression of
      immune response caused by nicotine.

PMID- 22475628
TI  - Down-regulation of PKCzeta in renal cell carcinoma and its clinicopathological
      implications.
AB  - BACKGROUND: Metastatic renal cell carcinoma (RCC) is highly resistant to systemic
      chemotherapy. Unfortunately, nearly all patients die of the metastatic and
      chemoresistant RCC. Recent studies have shown the atypical PKCzeta is an
      important regulator of tumorigenesis. However, the correlation between PKCzeta
      expression and the clinical outcome in RCC patients is unclear. We examined the
      level of PKCzeta expression in human RCC. METHODS: PKCzeta mRNA and protein
      expressions were examined by real-time polymerase chain reaction (PCR) and
      immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular
      cytotoxicity and proliferation were assessed by MTT. RESULTS: PKCzeta expression
      was significantly higher in normal than in cancerous tissues (P<0.0001) by real
      time PCR and IHC. Similarly, PKCzeta expression was down-regulated in four renal
      cancer cell lines compared to immortalized benign renal tubular cells.
      Interestingly, an increase of PKCzeta expression was associated with the elevated
      tumor grade (P=0.04), but no such association was found in TNM stage (P=0.13).
      Tumors with higher PKCzeta expression were associated with tumor size (P=0.048).
      Expression of higher PKCzeta found a poor survival in patients with high tumor
      grade. Down-regulation of PKCzeta showed the significant chemoresistance in RCC
      cell lines. Inactivation of PKCzeta expression enhanced cellular resistance to
      cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCzeta
      siRNA and inhibitor. CONCLUSIONS: PKCzeta expression was associated with
      tumorigenesis and chemoresistance in RCC.

PMID- 22475629
TI  - Investing in African research training institutions creates sustainable capacity
      for Africa: the case of the University of the Witwatersrand School of Public
      Health masters programme in epidemiology and biostatistics.
AB  - BACKGROUND: Improving health in Africa is a high priority internationally.
      Inadequate research capacity to produce local, relevant research has been
      identified as a limitation to improved population health. Increasing attention is
      being paid to the higher education sector in Africa as a method of addressing
      this; evidence that such investment is having the desired impact is required. A
      1998 3-year investment by the Special Programme for Research and Training in
      Tropical Diseases (TDR) in research training at the School of Public Health,
      University of the Witwatersrand, South Africa was reviewed to assess its' impact.
      METHODS: A descriptive cross-sectional survey of the 70 students registered for
      the masters programme in epidemiology & biostatistics from 2000-2005 was
      conducted. Data were collected from self-administered questionnaires. RESULTS:
      Sixty percent (42/70) of students responded. At the time of the survey 19% of
      respondents changed their country of residence after completion of the masters
      course, 14% migrated within Africa and 5% migrated out of Africa. Approximately
      half (47%) were employed as researchers and 38% worked in research institutions.
      Sixty percent reported research output, and four graduates were pursuing PhD
      studies. Government subsidy to higher education institutions, investments of the
      University of the Witwatersrand in successful programmes and ongoing bursaries
      for students to cover tuition fees were important for sustainability.
      CONCLUSIONS: Investing in African institutions to improve research training
      capacity resulted in the retention of graduates in Africa in research positions
      and produced research output. Training programmes can be sustained when national
      governments invest in higher education and where that funding is judiciously
      applied. Challenges remain if funding for students bursaries is not available.

PMID- 22475630
TI  - Preparation and characterization of PEM-coated alginate microgels for controlled
      release of protein.
AB  - In this study, calcium-alginate microgels coated with a polyelectrolyte
      multilayer (PEM) were fabricated as a controlled-release system. This system was
      constructed via an electrostatic droplet generation technique followed by a layer
      by-layer (LbL) self-assembly technique. The electrostatic droplet generation
      technique was reported as an easy method of preparing microgels, due to their
      mild preparation conditions and ability to preserve the biological activity of
      the encapsulated drugs. With the LbL self-assembly technique, the PEM could be
      fabricated on the microgels attributed to the electrostatic attraction between
      positive-charged chitosan (Chi) and negative-charged dextran sulfate (Dex). The
      properties of the prepared microgels were investigated using dynamic laser
      scattering (DLS), scanning electron microscopy (SEM), x-ray photoelectron
      spectroscopy (XPS), Fourier transform infrared (FTIR) spectrum and zeta potential
      analyzer. In vitro release study indicated that the initial burst release of the
      bovine serum albumin (BSA) from PEM-coated microgels was less compared to the
      uncoated microgels (19% versus 31% in 24 h). In addition, the sustained release
      of BSA from the PEM-coated microgels was recorded up to 1 month without any
      damage to BSA integrity. Thus, our results demonstrated that the PEM-coated
      microgels not only prolonged the release time, but also relieved the initial
      burst problem to some degree and preserved the biological activity of the
      encapsulated drugs. Moreover, the release rate of BSA could be regulated by
      controlling the number of deposited layers. In conclusion, this study presented
      an easy yet effective method for the controlled, sustained release of biological
      macromolecules.

PMID- 22475631
TI  - Parental socioeconomic status and soft drink consumption of the child. The
      mediating proportion of parenting practices.
AB  - The hypothesis of this study is twofold and states that parental socioeconomic
      status has an effect on the soft drink consumption of the child, and that this
      effect is mediated by the soft drink related parenting practices. One thousand
      six hundred and thirty-nine parents of 2.5-7 year old children from 34 Flemish
      pre-primary and primary schools, completed a self-administered questionnaire on
      sociodemographic characteristics, soft drink consumption and soft drink related
      parenting practices. Causal mediation analyses showed an effect of socioeconomic
      status on soft drink consumption of the child: children from high socioeconomic
      status consume 0.42 times the amount of soft drinks of children from lower
      socioeconomic status. Interestingly, this effect is almost entirely mediated by
      three soft drink parenting practices: soft drinks served at meals, the child can
      take soft drink whenever he or she wants and having soft drinks at home.

PMID- 22475632
TI  - Spectral imaging in preclinical research and clinical pathology.
AB  - Spectral imaging methods are attracting increased interest from researchers and
      practitioners in basic science, pre-clinical and clinical arenas. A combination
      of better labeling reagents and better optics creates opportunities to detect and
      measure multiple parameters at the molecular and cellular level. These tools can
      provide valuable insights into the basic mechanisms of life, and yield diagnostic
      and prognostic information for clinical applications. There are many
      multispectral technologies available, each with its own advantages and
      limitations. This chapter will present an overview of the rationale for spectral
      imaging, and discuss the hardware, software and sample labeling strategies that
      can optimize its usefulness in clinical settings.

PMID- 22475633
TI  - Neuronal NF-kappaB ablation does not influence neuro-axonal degeneration in
      experimental autoimmune demyelination.
AB  - Neuro-axonal damage is a major hallmark of multiple sclerosis (MS). To date, not
      much is known on the underlying mechanisms of neuronal degeneration. In disease
      model myelin oligodendrocyte glycoprotein induced experimental autoimmune
      encephalomyelitis (MOG-EAE), there is a significant loss of alpha motorneurons in
      the cervical as well as thoracic and lumbar spinal cord. We further investigate
      the role of activated NF-kappaB for neuronal damage in a conditional ablation
      mouse model. A calcium calmodulin kinase II promoter-driven tetracycline
      transactivator is employed to regulate the expression of a human transdominant
      negative IkappaB-alpha mutant in the basal forebrain and selected neuronal
      subpopulations in the cerebellum and spinal cord including cerebellar Purkinje
      cells and spinal cord alpha motorneurons. In these mice with conditional neuronal
      NF-kappaB ablation, the clinical course of MOG-EAE, parameters of inflammation
      and axonal densities in the spinal cord white and grey matter as well as numbers
      of alpha motorneurons are not different to littermate controls. In conclusion,
      neuronal NF-kappaB ablation does not modulate neurodegeneration in autoimmune
      demyelination.

PMID- 22475634
TI  - Diabetes and cardiovascular risk factor controls in Thai type 2 diabetes with no
      history of cardiovascular complications; situation and compliance to diabetes
      management guideline in Thailand.
AB  - BACKGROUND: Cardiovascular complication is one of the most important issues
      causing morbidity and death in diabetic patients. Primary prevention is a key to
      prevent this complication. AIMS: The objective was to study the situations of
      diabetes and cardiovascular risk factor controls in Thai type 2 diabetic patients
      who had no history of cardiovascular complication at a university hospital in
      Thailand after the Thai diabetes management guideline was recently launched.
      METHODS: The study was a cross-sectional survey in type 2 diabetes patients with
      no history of cardiovascular disease. Seven hundred and fourteen patients were
      enrolled in the study and 54.3% were females. The data were collected
      retrospectively from out-patient medical records and an electronic data base for
      the patients who were followed up at the hospital during January-December 2010.
      The most recent laboratory values were utilized in the analysis. RESULTS: 70%-90%
      of all patients were checked for HbA1c and lipid profiles (LDL-C, total
      cholesterol, triglycerides) at least once a year. It was observed that only 28%
      of the patients had HbA1c<6.5%. Furthermore, the percentages of the patients who
      had blood pressure <130/80 mmHg, and who had LDL-C<100 mg/dL were 28% and 41%,
      respectively. CONCLUSION: Even though the practice guideline has been launched
      since 2008, diabetes, hypertension and dyslipidemia were still poorly controlled.
      Further study is recommended to identify factors influencing these outcomes as
      well as the policy of diabetic care in Thailand is needed to be seriously
      implemented.

PMID- 22475635
TI  - Influence of the glucose-lowering rate on left ventricular function in patients
      with type 2 diabetes and coronary heart disease.
AB  - BACKGROUND: The optimal methods for glucose control and reduction in the risk of
      cardiovascular disease are controversial. Findings from recent clinical trials
      have shown different viewpoints on the advantages and disadvantages of intensive
      lowering of glucose. We used echocardiography to explore the influence of the
      glucose-lowering rate on left ventricular function in patients with type 2
      diabetes mellitus (T2DM). We also attempted to discover an effective glucose
      lowering rate for patients with type 2 diabetes mellitus and coronary heart
      disease (T2DM-CHD). METHODS: A total of 132 cases of T2DM and 135 cases of T2DM
      CHD received intensive glucose therapy. After measuring left ventricular ejection
      fraction (LVEF) and the E/A ratio, variations and correlation factors were
      evaluated. RESULTS: LVEF was significantly higher than before intensive therapy
      in the T2DM group with a glucose-lowering rate of <=6mmol.L(-1).d(-1) (P<.05).
      LVEF was significantly lower than before intensive therapy in the T2DM-CHD group
      with a glucose-lowering rate >4mmol.L(-1).d(-1) (P<.05), whereas at the end of
      follow-up (3months), LVEF increased and no significant difference was observed
      between subgroups (P>.05). The E/A ratio increased among all subgroups after
      intensive therapy (P<.05). The waist-hip ratio, duration of T2DM, and age had a
      linear regression relationship with variations in LVEF before and after intensive
      therapy. CONCLUSIONS: For patients with T2DM and CHD, an excessively fast glucose
      lowering rate could impair left ventricular systolic function. Long-term, good
      control of blood glucose could restore the impaired left ventricular systolic
      function caused by an excessively fast glucose-lowering rate. After intensive
      therapy, left ventricular diastolic function improved among all subgroups
      regardless of the glucose-lowering rate and CHD.

PMID- 22475636
TI  - Metabolomic analysis of sex specific metabolites in gonads of the mussel, Mytilus
      edulis.
AB  - Marine mussels have been used as sentinel organisms to monitor exposure to a
      variety of chemical contaminants, including endocrine disrupting chemicals, in
      the aquatic environment. Although they are an important species for use in
      ecotoxicology investigations, information on their reproductive physiology and
      biochemistry is fragmentary. Mass spectrometry-based profiling techniques are
      increasingly being used to study how the metabolome of an organism changes as a
      result of tissue differentiation, disease or in response to environmental
      stressors. In this study, ultraperformance liquid chromatography-time-of-flight
      mass spectrometry (UPLC-TOFMS) was used to investigate sex specific differences
      in the mussel metabolome in order to further investigate the reproductive
      physiology of this species. Using this method, a comparison of female and male
      mantle tissues containing mature gonad, revealed significant differences in
      glycerophosphatidylcholine (PC) and lysophosphatidylcholine (LPC) metabolites. A
      number of other unidentified metabolites, including those putatively identified
      as conjugated sterols, were also differentially expressed between male and female
      mantle/gonadal tissue.

PMID- 22475637
TI  - Lymphoma of the thyroid and head and neck.
AB  - The most common sites for extra-nodal lymphoma of the head and neck are
      Waldeyer's ring, most frequently the tonsil, and the salivary glands, usually the
      parotid. Most are B-cell malignancies and stage IE or IIE at diagnosis. Marginal
      zone lymphoma of mucosa-associated lymphoid tissue type is particularly
      associated with inflammatory conditions in the thyroid and salivary glands. The
      management of extra-nodal lymphoma in the head and neck is similar to nodal B
      cell lymphoma with R-CHOP chemotherapy followed by radiotherapy, recommended for
      early-stage high-grade disease, and radiotherapy alone for localised low-grade
      lymphoma. The notable exception is NK/T-cell lymphoma of nasal type where
      radiotherapy is critically important and recommended to a higher dose, partly
      because of poor response to anthracycline-based chemotherapy regimens like CHOP.
      Given the higher doses required and the proximity of critical normal structures,
      intensity-modulated radiotherapy should be considered for these tumours.

PMID- 22475638
TI  - Proteomics and the Trypanosoma brucei cytoskeleton: advances and opportunities.
AB  - Trypanosoma brucei is the etiological agent of devastating parasitic disease in
      humans and livestock in sub-saharan Africa. The pathogenicity and growth of the
      parasite are intimately linked to its shape and form. This is in turn derived
      from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage
      directly beneath the pellicular membrane and numerous other cytoskeletal
      structures such as the flagellum. The parasite undergoes extreme changes in
      cellular morphology during its life cycle and cell cycles which require a high
      level of integration and coordination of cytoskeletal processes. In this review
      we will discuss the role that proteomics techniques have had in advancing our
      understanding of the molecular composition of the cytoskeleton and its functions.
      We then consider future opportunities for the application of these techniques in
      terms of addressing some of the unanswered questions of trypanosome cytoskeletal
      cell biology with particular focus on the differences in the composition and
      organisation of the cytoskeleton through the trypanosome life-cycle.

PMID- 22475639
TI  - Performance analysis of efforts towards promotion of corneal donation at a
      tertiary care trauma center in India.
AB  - PURPOSE: To identify the number of potential donors from trauma-related deaths
      and examine the extent of loss of opportunity at different levels for eye
      donation. METHODS: A retrospective review of the death records from the mortuary
      of Jai Prakash Narayan Apex Trauma Centre and National Eye Bank at All India
      Institute of Medical Sciences was conducted for the period between January 2008
      and August 2009. All cases with trauma-related deaths were included in the study.
      Cases with known contraindications to eye donation were excluded from the study.
      The main outcome measure was "lost opportunity cases" where the families of
      eligible donors were not approached. The secondary outcome measure was successful
      procurement rate. RESULTS: The total number of trauma-related deaths noted during
      the study period was 1584. One hundred cases were excluded from the study because
      the records were either incomplete or not readily available. A total of 1066
      cases were identified as medically suitable potential eye donors. The death
      autopsy interval was 12 hours or less in 425 cases and >12 hours in 641 cases.
      Among eligible donors, there were 831 (78%) lost opportunity cases. Among 235
      families approached, only 20 (8.5%) agreed to eye donation. Overall, successful
      eye donation was possible in only 20 (1.9%) of the eligible trauma-related
      deaths. CONCLUSIONS: Trauma-related deaths form a major pool for potential tissue
      donors. Only about one fifth of the medically eligible cases could be approached
      for counseling. A potentially large donor pool of trauma-related deaths is
      compromised by the lost opportunity cases and the low donation rate. Efforts are
      needed to augment existing administrative and manpower resources to increase the
      corneal procurement rate in the Indian population.

PMID- 22475640
TI  - Use of the breathe right external nasal dilator strip as temporary eyelid splint.

PMID- 22475641
TI  - Clinical utility of objective tests for dry eye disease:  variability over time
      and implications for clinical trials and disease management.
AB  - PURPOSE: To evaluate the efficacy of commonly used biomarkers in dry eye disease
      management in a longitudinal observational case series study followed by an
      interventional study in a subset of subjects treated with cyclosporine A (0.05%).
      METHODS: Bilateral tear osmolarity, Schirmer, tear film breakup time (TBUT),
      staining, meibomian grading, and Ocular Surface Disease Index were measured for a
      period of 3 consecutive months in participants recruited from a clinic-based
      population at 2 study sites. Fifty-two subjects completed the study (n = 16
      mild/moderate, n = 36 severe; age, 47.1 +/- 16.1 years). After the 3-month
      observation period, severe dry eye patients were prescribed topical cyclosporine
      A and evaluated for an additional 3 months. RESULTS: Tear osmolarity (8.7 +/-
      6.3%) exhibited significantly less variability over a 3-month period than corneal
      staining (12.2 +/- 8.8%, P = 0.040), conjunctival staining (14.8 +/- 8.9%, P =
      0.002), and meibomian grading (14.3 +/- 8.8%, P < 0.0001) across the entire
      patient population. Osmolarity also demonstrated less variation than TBUT (11.7
      +/- 9.0%, P = 0.059), Schirmer tests (10.7 +/- 9.2%, P = 0.67), and Ocular
      Surface Disease Index (9.3 +/- 7.8%, P = 0.94), although the differences were not
      significant. Variation in osmolarity was less for mild dry eye patients (5.9 +/-
      3.1%) than severe dry eye patients (10.0 +/- 6.9%, P = 0.038). After treatment,
      average osmolarity and variability were lowered from 341 +/- 18 mOsm/L to 307 +/-
      8 mOsm/L (P < 0.0001, n = 10). A downward trend in symptoms followed changes in
      osmolarity, declining from 44 +/- 17 mOsm/L to 38 +/- 18 mOsm/L (P = 0.35). None
      of the other signs demonstrated a change after treatment. CONCLUSIONS: Over a 3
      month period, tear film osmolarity was found to have the lowest variability among
      commonly used signs of dry eye disease. Reductions in osmolarity preceded changes
      in symptoms during therapy.

PMID- 22475642
TI  - Prostaglandin E2 suppresses poly I: C-stimulated cytokine production via EP2 and
      EP3 in immortalized human corneal epithelial cells.
AB  - PURPOSE: We previously reported that prostaglandin (PG) E2 acts as a ligand for
      prostaglandin E receptor 3 (EP3) in conjunctival epithelial cells, that it
      downregulates the progression of experimental murine allergic conjunctivitis, and
      that in human conjunctival epithelial cells it modulates the expression of
      polyI:C-induced proinflammatory genes via prostaglandin E receptor 2 (EP2) and
      EP3, suggesting that PGE2 might have important roles in ocular surface
      inflammation such as allergic conjunctivitis. Here, we investigated whether PGE2
      also downregulates polyI:C-induced cytokine production in human corneal
      epithelial cells. METHODS: We used enzyme-linked immunosorbent assay and
      quantitative reverse transcription-polymerase chain reaction to examine the
      effects of PGE2 on polyI:C-induced cytokine expression by immortalized human
      corneal-limbal epithelial cells (HCLE). Using reverse transcription-polymerase
      chain reaction, we examined the messenger RNA (mRNA) expression of the PGE2
      receptor, EP1-4. RESULTS: PGE2 significantly attenuated the expression of CC
      chemokine ligand (CCL)5 (P < 0.0005), CCL20 (P < 0.0005), C-X-C chemokine
      (CXCL)10 (P < 0.0005), CXCL11 (P < 0.05), and interleukin (IL)-6 (P < 0.005) in
      human corneal-limbal epithelial cells. Human corneal epithelial cells manifested
      the mRNA expression of EP2, EP3, and EP4, but not EP1. The EP2 agonist
      significantly suppressed the polyI:C-induced expression of CCL5 (P < 0.005),
      CXCL10 (P < 0.0005), and CXCL11 (P < 0.05) but not of CCL20 and IL-6. The EP3
      agonist significantly suppressed the expression of CCL5 (P < 0.05), CCL20 (P <
      0.005), CXCL10 (P < 0.0005), CXCL11 (P < 0.0005), and IL-6 (P < 0.005). The EP4
      agonist failed to suppress cytokine production induced by polyI:C stimulation.
      CONCLUSIONS: Our results show that in human corneal epithelial cells, PGE2
      attenuated the mRNA expression and production of CCL5, CXCL10, and CXCL11 via
      both EP2 and EP3, and that the mRNA expression and production of CCL20 and IL-6
      was attenuated only by EP3.

PMID- 22475643
TI  - Photorefractive keratectomy modification of postkeratoplasty anisometropic
      refractive errors.
AB  - PURPOSE: To evaluate the efficacy, refractive predictability and stability, and
      complications of photorefractive keratectomy (PRK) with adjunctive mitomycin C
      (MMC) in patients with postkeratoplasty anisometropia. METHODS: A retrospective
      review was carried out of all cases of PRK performed for postkeratoplasty
      anisometropia with the VISX Star S4 excimer laser with MMC between January 1,
      2004, and December 31, 2008. The main outcome measures were best spectacle
      corrected distance visual acuity (CDVA) and patient tolerance of full spectacle
      refractive correction. Secondary outcome measures were uncorrected distance
      visual acuity (UDVA), refractive accuracy and stability, and complications.
      RESULTS: Twenty cases met the inclusion criteria. At 6 months, the spectacle CDVA
      had improved from a preoperative mean of 20/50 to 20/30 (P = 0.01). Ten eyes
      (50%) gained 2 or more lines of CDVA. Eighteen eyes (90%) had a CDVA of 20/40 or
      better. All 20 patients (100%) were subjectively satisfied with full binocular
      spectacle correction. There was an improvement in UDVA from a preoperative mean
      of 20/282 to 20/52 (P < 0.001). Thirteen patients (65%) had an UDVA of 20/40 or
      better. There was a reduction in the mean refractive spherical equivalent from 
      5.2 to -0.9 diopters (D), in myopia from -7.6 to -1.8 D, and in astigmatism from
      4.9 to 2.0 D. No significant change in visual acuity or refractive error occurred
      between 3 and 12 months. No sight-threatening complications occurred. One eye
      (5%) lost 2 lines of CDVA. CONCLUSIONS: PRK with adjunctive MMC is an effective
      method of reducing postkeratoplasty anisometropia and providing satisfactory
      spectacle rehabilitation.

PMID- 22475644
TI  - First report of traumatic globe rupture after femtosecond laser-assisted
      penetrating keratoplasty.
AB  - PURPOSE: To describe the first reported case of traumatic globe rupture after
      femtosecond laser-assisted penetrating keratoplasty. METHODS: A 21-year-old
      Hispanic man suffered a corneal laceration after blunt trauma leading to a
      visually significant corneal scar and aphakia. RESULTS: The patient underwent
      femtosecond laser-assisted penetrating keratoplasty using a zigzag-shaped wound
      with secondary intraocular lens placement. Eighteen months after surgery, he
      suffered another blunt trauma resulting in inferior dehiscence of his inferior
      penetrating keratoplasty wound, loss of uveal tissue, and extrusion of the
      scleral-fixated posterior chamber intraocular lens. The patient underwent repair
      of the wound dehiscence. CONCLUSIONS: Despite the theoretical advantages
      conferred by a shaped graft-host junction, a shaped penetrating keratoplasty
      wound created with femtosecond laser can still be subject to dehiscence from
      trauma.

PMID- 22475645
TI  - Comparison of transforming growth factor beta1 concentrations in the ovaries of
      rats stimulated by human menopausal gonadotropin or recombinant follicle
      stimulating hormone.
AB  - OBJECTIVE: To compare the effects of human menopausal gonadotropins (hMG) and
      recombinant follicle stimulating hormone (rFSH) on transforming growth factor
      (TGF) beta1 concentration in the rat ovary. STUDY DESIGN: Twenty-one fertile
      Wistar-Albino rats were divided into 3 groups of 7. Groups 1, 2 and 3 were
      injected with saline, hMG or rFSH, respectively, over 5 days, after which they
      underwent ovariectomy. Hematoxylin and eosin (H&E) staining was used for
      histological examination. TGF beta1 staining levels in ovarian stroma, vessel
      walls, granulosa cells of Graafian follicles and corpus luteum cells were
      investigated immunohistochemically. RESULTS: On histological examination, the
      number of smaller antral follicles was higher in the control group, while there
      were more and larger antral follicles in the hyperstimulated groups. There were
      statistically significant differences in staining in vessel walls and granulosa
      cells between the control and stimulated groups. Both stimulation protocols
      caused an increased TGF beta1 concentration in vessel walls, while there was weak
      staining in granulosa cells in the treatment groups compared to the control group
      (p<0.05). There were no significant differences in staining scores between the
      two treatment groups (p>0.05). CONCLUSIONS: The effects of two different
      gonadotropin preparations on TGF beta1 concentrations in different localizations
      in the rat ovaries are comparable. It may be postulated that the luteinizing
      hormone (LH) content of hMG contributes little or nothing to the TGF beta1
      mediated angiogenesis.

PMID- 22475646
TI  - A novel nanoparticle delivery system for in vivo targeting of the sciatic nerve:
      impact on regeneration.
AB  - AIM: Innovative solutions in the development of drug delivery systems targeting
      the nerve tissue are awaited. In this regard, a novel system for the delivery of
      drugs to the sciatic nerve was created using nanomedical principles. MATERIALS &
      METHODS: Chitosan was the vehicle material used in the experiment. Heparin bound
      to growth factors has been administered to enhance peripheral nerve regeneration,
      and since heparin possesses the appropriate charge to be able to form
      nanoparticles with chitosan, it appears to be a good candidate to base this new
      delivery system on. RESULTS: Maximal absorption took place throughout the
      extracellular matrix at day 15. No major inflammatory response was observed,
      indicating that this is a safe and biocompatible system for drug delivery to
      nerves. Sensorimotor performance and nerve regeneration of mice receiving these
      nanoparticles were superior as compared with controls. CONCLUSION: Our work
      demonstrates a versatile nanoparticle delivery system that successfully targets
      drugs 'in vivo' to the sciatic nerve, opening novel avenues in the field of
      nanomedicine to the design of therapeutic strategies that enhance axonal
      regeneration.

PMID- 22475647
TI  - Efficient internalization and intracellular translocation of inhaled gold
      nanoparticles in rat alveolar macrophages.
AB  - AIM: To investigate the relationship of alveolar macrophages and inhaled
      nanoparticles (NPs) in the lung. MATERIALS & METHODS: Rats were exposed by
      inhalation to 16-nm gold NPs for 6 h, and ultramicroscopic observation on the
      frequency and localization of gold NPs within lavaged macrophages was performed
      for 7 days. RESULTS & DISCUSSION: The majority of macrophages examined on day 0
      (94%) contained internalized gold NPs, and the percentage decreased to 59% on day
      7. Gold NPs were exclusively found within cytoplasmic vesicles. On day 0, most
      gold NPs appeared to be individual or slightly agglomerated, while they were
      frequently agglomerated on day 7. CONCLUSION: Alveolar macrophages efficiently
      internalized NPs by endocytosis, and rearrangements of vesicles and of NPs in the
      vesicles of macrophages occurred.

PMID- 22475648
TI  - Minimally invasive drug delivery to the cochlea through application of
      nanoparticles to the round window membrane.
AB  - Direct drug delivery to the cochlea is associated with the risk of irreversible
      damage to the ear. In this study, liposome and polymersome nanoparticles (NPs),
      both formed from amphiphilic molecules (lipids in liposomes and block copolymers
      in polymersomes), were tested as potential tools for drug delivery to the cochlea
      via application onto the round window membrane in adult mice (strain C3H). One
      day after round window membrane application, both types of NPs labeled with
      fluorescent markers were identified in the spiral ganglion in all cochlear turns
      without producing any distinct morphological or functional damage to the inner
      ear. NPs were detected, although to a lesser extent, in the organ of Corti and
      the lateral wall. The potential of liposome and polymersome NPs as therapeutic
      delivery systems into the cochlea via the round window membrane was evaluated
      using disulfiram, a neurotoxic agent, as a model payload. Disulfiram-loaded NP
      delivery resulted in a significant decrease in the number of spiral ganglion
      cells starting 2 days postapplication, with associated pronounced hearing loss
      reaching 20-35 dB 2 weeks postapplication as assessed through auditory brainstem
      responses. No changes in hair cell morphology and function (as assessed by
      recording otoacoustic emissions) were detected after disulfiram-loaded NP
      application. No effects were observed in controls where solution of free
      disulfiram was similarly administered. The results demonstrate that liposome and
      polymersome NPs are capable of carrying a payload into the inner ear that elicits
      a biological effect, with consequences measurable by a functional readout.

PMID- 22475649
TI  - Modulation of inflammatory signaling and cytokine release from microglia by
      celastrol incorporated into dendrimer nanocarriers.
AB  - AIM: This study investigates the capacity of a potent anti-inflammatory
      nanomedicine, celastrol, incorporated into poly(amidoamine) dendrimers, to
      inhibit endotoxin-mediated signaling in microglia. MATERIALS & METHODS: Celastrol
      was incorporated into amino (Cel/G4-NH(2)) and hydroxyl (Cel/G4-OH) terminus
      poly(amidoamine) (G4) dendrimers. Cell viability, release of nitric oxide, IL-6,
      TNF-alpha and activation of MAPK (e.g., p38 and JNK) and NF-kappaB were assessed
      in endotoxin (i.e., lipopolysaccharide) stimulated microglial cells. RESULTS: G4
      OH and G4-NH(2) increased celastrol aqueous solubility by seven- and 12-fold,
      respectively. G4-OH and Cel/G4-OH suppressed lipopolysaccharide-mediated release
      of proinflammatory mediators, such as nitric oxide and IL-6, but not TNF-alpha,
      without reducing microglial cell viability, while Cel/G4-NH(2) potentiated
      cytotoxicity and cytokine release. Blockade of proinflammatory signaling was
      accompanied by attenuation of p38 MAPK activation. CONCLUSION: This study
      supports the potential use of poly(amidoamine) dendrimers for effective anti
      inflammatory therapy in the chronically inflamed CNS.

PMID- 22475650
TI  - Nanowires precisely grown on the ends of microwire electrodes permit the
      recording of intracellular action potentials within deeper neural structures.
AB  - AIMS: Nanoelectrodes are an emerging biomedical technology that can be used to
      record intracellular membrane potentials from neurons while causing minimal
      damage during membrane penetration. Current nanoelectrode designs, however, have
      low aspect ratios or large substrates and thus are not suitable for recording
      from neurons deep within complex natural structures, such as brain slices.
      MATERIALS & METHODS: We describe a novel nanoelectrode design that uses nanowires
      grown on the ends of microwire recording electrodes similar to those frequently
      used in vivo. RESULTS & DISCUSSION: We demonstrate that these nanowires can
      record intracellular action potentials in a rat brain slice preparation and in
      isolated leech ganglia. CONCLUSION: Nanoelectrodes have the potential to
      revolutionize intracellular recording methods in complex neural tissues, to
      enable new multielectrode array technologies and, ultimately, to be used to
      record intracellular signals in vivo.

PMID- 22475651
TI  - Nkx1-2 is a transcriptional repressor and is essential for the activation of
      Brachyury in P19 mouse embryonal carcinoma cell.
AB  - Activation of Wnt/beta-catenin signaling is crucial for the differentiation of
      pluripotent stem cells, namely the epiblast, embryonic stem, and embryonal
      carcinoma cells, into mesendoderm. However, downstream events of Wnt/beta-catenin
      signaling that control the formation of mesendoderm are still unclear. In the
      present study, we used mouse P19 embryonal carcinoma cells as a model, and
      identified a homeodomain protein Nkx1-2 as a key regulator of mesendoderm
      formation. In the mouse embryo, Nkx1-2 was expressed in the primitive streak, in
      which the nascent mesendoderm emerges. In P19 cells, the expression of Nkx1-2 was
      activated by Wnt/beta-catenin signaling independently of Brachyury, an
      evolutionary conserved early mesendoderm gene. In contrast, the expression of
      Nkx1-2 was both necessary and sufficient for the activation of Brachyury. Nkx1-2
      acted as a transcriptional repressor to mediate the action of Wnt/beta-catenin
      signaling to activate the Brachyury expression. We found Tcf3 as a potential
      target of gene repression by Nkx1-2, and the down-regulation of Tcf3 was partly
      required for effective activation of Brachyury by Wnt/beta-catenin signaling.
      These results suggest that Nkx1-2 is a critical component of the gene regulatory
      network that operates downstream of Wnt/beta-catenin signaling to regulate the
      formation of mesendoderm.

PMID- 22475652
TI  - High plasma uric acid concentration: causes and consequences.
AB  - High plasma uric acid (UA) is a precipitating factor for gout and renal calculi
      as well as a strong risk factor for Metabolic Syndrome and cardiovascular
      disease. The main causes for higher plasma UA are either lower excretion, higher
      synthesis or both. Higher waist circumference and the BMI are associated with
      higher insulin resistance and leptin production, and both reduce uric acid
      excretion. The synthesis of fatty acids (tryglicerides) in the liver is
      associated with the de novo synthesis of purine, accelerating UA production. The
      role played by diet on hyperuricemia has not yet been fully clarified, but high
      intake of fructose-rich industrialized food and high alcohol intake (particularly
      beer) seem to influence uricemia. It is not known whether UA would be a causal
      factor or an antioxidant protective response. Most authors do not consider the UA
      as a risk factor, but presenting antioxidant function. UA contributes to > 50% of
      the antioxidant capacity of the blood. There is still no consensus if UA is a
      protective or a risk factor, however, it seems that acute elevation is a
      protective factor, whereas chronic elevation a risk for disease.

PMID- 22475654
TI  - Plasmodium knowlesi: from Malaysia, a novel health care threat.
AB  - Epidemic foci of Plasmodium knowlesi malaria have been identified during the past
      ten years in Malaysia, in particular in the States of Sarawak and Sabah (Malaysia
      Borneo), and in the Pahang region (peninsular Malaysia). Based on a review of the
      available recent international literature, the authors underline the importance
      of molecular biology examinations, polymerase chain reactions (PCR), performed
      with primers specific for P. knowlesi, since the current microscopic examination
      (haemoscope) may fail to distinguish P. knowlesi from Plasmodium malariae, due to
      the very similar appearance of the two parasites. P. knowlesi has been described
      as the causal agent of life-threatening and lethal forms of malaria: its clinical
      picture is more severe when compared with that of P. malariae, since the disease
      is characterized by greater parasitaemia, as opposed to that documented in the
      course of P. malariae disease. The most effective carrier is Anopheles
      leucosphyrus: this mosquito is attracted by both humans and monkeys. Among
      primates, the natural hosts of P. knowlesi are Macaca fascicularis and Macaca
      nemestina, while Saimiri scirea and Macaca mulatta, which cannot become infected
      in nature, may be useful in experimental models. When underlining the potentially
      severe evolution, we note the key role played by prompt disease recognition,
      which is expected to be more straightforward in patients monitored in endemic
      countries at high risk, but should be carefully implemented for subjects being
      admitted to hospital in Western countries suffering from the typical signs and
      symptoms of malaria, after travelling in South-East Asia where they were engaged
      in excursions in the tropical forest (trekking, and similar outdoor activities).
      In these cases, the diagnosis should be prompt, and suitable treatment should
      follow. According to data in the literature, in non-severe cases chloroquine
      proves very effective against P. knowlesi, achieving the disappearance of signs
      and symptoms in 96% of cases after only 24 hours after treatment start. In the
      light of the emerging epidemiological data, P. knowlesi should be added to
      Plasmodium vivax, Plasmodium ovale, P. malariae, and Plasmodium falciparum, as
      the fifth aetiological agent of malaria. During the next few years, it will
      become mandatory to plan an appropriate surveillance program of the
      epidemiological evolution, paying also great attention to the clinical features
      of patients affected by P. knowlesi malaria, which are expected to worsen
      according to the time elapsed; some studies seem to point out greater severity
      according to increased parasitaemia, paralleling the increased interhuman
      infectious passages of the plasmodium.

PMID- 22475653
TI  - Genetic predictors of fatigue in prostate cancer patients treated with androgen
      deprivation therapy: preliminary findings.
AB  - BACKGROUND: Fatigue is a common and distressing side effect of androgen
      deprivation therapy (ADT) for prostate cancer. The goal of the current study was
      to examine the relationship between changes in fatigue following initiation of
      ADT and single nucleotide polymorphisms (SNPs) in three pro-inflammatory cytokine
      genes: interleukin-1 beta (IL1B), interleukin-6 (IL6), and tumor necrosis factor
      alpha (TNFA). METHODS: As part of a larger study, men with prostate cancer (n =
      53) were recruited prior to initiation of ADT. Fatigue was assessed at
      recruitment and 6 months after initiation of ADT. DNA was extracted from blood
      drawn at baseline. RESULTS: Patients with the IL6-174 (rs1800795) G/C or C/C
      genotype displayed greater increases in fatigue intrusiveness, frequency, and
      duration than the G/G genotype (p values <= 0.05), although inclusion of age,
      race, and baseline depressive symptomatology in the model attenuated these
      relationships (p values <= 0.09). Patients with the TNFA-308 (rs1800629) G/A
      genotype showed greater increases in fatigue severity than the G/G genotype (p =
      0.02). IL1B-511 (rs16944) genotype did not significantly predict changes in
      fatigue (p values >0.46). Patients with higher numbers of variants displayed
      greater increases in fatigue duration and interference (p values <= 0.02) than
      patients with lower numbers of variants. CONCLUSIONS: Prostate cancer patients
      treated with ADT who carry variant alleles of the IL6 and TNFA genes are
      susceptible to heightened fatigue. These preliminary data lend support for the
      role of genetic variation in the development of cancer-related fatigue secondary
      to ADT. Findings are relevant to attempts to develop personalized approaches to
      cancer treatment.

PMID- 22475655
TI  - [Cytomegalovirus infection in immunocompetent patients. Clinical and
      immunological considerations].
AB  - Cytomegalovirus primary infection is considered dangerous for some kinds of
      patients: immunocompromised (HIV-infected and transplanted patients), newborns
      with congenital infection, and immunocompetent patients in critical condition.
      CMV infection is usually asymptomatic or only mildly symptomatic in
      immunocompetent hosts. We collected all cases of acute CMV infection that came to
      our attention during the period November 2009 - May 2011 to analyze their
      clinical features. Immunoenzymatic methods (ELISA) were used for the detection of
      specific IgM and IgG antibodies in every case. We observed 73 cases of acute CMV
      infection. The male-female ratio was 1.5/1. The average age was 36.4. All the
      patients had fever, 16 (22%) pharyngitis, only 9 (12.3%) lymphadenopathy. The
      most common complications were hepatitis, encephalitis, pericarditis and
      pneumonia. Unknown genetic factors may greatly influence the clinical expression
      of the illness.

PMID- 22475656
TI  - [Diagnostic sensitivity of QuantiFERON-TB Gold In-Tube and tuberculin skin test
      in active tuberculosis: influence of immunocompromission and radiological extent
      of disease].
AB  - Tuberculosis (TB) is a pathology whose control is still unsatisfactory at global
      level. Traditional diagnostic techniques for active TB diagnosis are inadequate:
      the diagnostic gold standard is the cultural exam which suffers from lengthy
      processing and requires highly specialized laboratories. This study analyzed the
      diagnostic sensitivity of the tuberculin skin test (TST) and QuantiFERON-TB Gold
      In-Tube (QFT-IT) in 135 active, microbiologically confirmed TB cases. Sensitivity
      was 76% for both tests and reached cumulative levels close to 90%. QFT-IT
      revealed a statistically higher sensitivity than TST in a group of patients
      affected by various causes of immunosuppression, but was less sensitive in
      subjects with low levels of circulating CD4+ cells. The number of circulating
      CD4+ cells showed a direct correlation with the stimulated IFN-gamma production.
      QFT-IT also demonstrated a decreased IFN-gamma production, with a significant
      sensitivity reduction, in patients affected by advanced forms of pulmonary TB.

PMID- 22475657
TI  - [Study on in vitro susceptibility of Candida spp. isolated from blood culture].
AB  - In recent years the incidence of bloodstream infections due to Candida species
      has progressively increased, partly due to the more critical conditions of
      hospitalized patients. There has been a significant increase in immune
      compromised, diabetic and/or elderly patients, also with venous access, with a
      subsequent increase in Candida species isolated from bloodstream infections. In
      2009-2010 in the hospitals of Mestre and Venice we isolated 123 Candida species
      from bloodstream infections: 59 Candida albicans, 28 Candida parapsilosis, 12
      Candida glabrata, 9 Candida tropicalis, and 4 Geotrichum capitatum, while the 11
      others belong to 8 different species. We calculated MIC for the following
      antifungal agents: fluconazole, itraconazole, voriconazole, 5-flucytosine,
      amphotericin B and caspofungin.

PMID- 22475658
TI  - Liver biopsy in chronic hepatitis C: the experience of 15 Italian wards of
      infectious diseases.
AB  - To evaluate the impact of liver histology on the management of HCV-related
      chronic hepatitis, 281 patients with chronic HCV infection who consecutively
      underwent percutaneous liver biopsy (LB) at one of the 15 participating Italian
      Units of Infectious Diseases were investigated in 2005. Demographic,
      aetiological, laboratory and clinical data and information on methods applied to
      perform ultrasonography (US) and LB were recorded. Males predominated (61.6%),
      mean age was 47.5 years and the mean BMI 22.3. In each case LB was US-guided or
      US-assisted. An 18-gauge Menghini-type needle was used in 203 (72.2%) cases. The
      length of the specimen ranged between 1.5 and 5 cm in 279 (99.3%) cases, it was
      smaller in two cases, but the diagnosis was still possible. Haemoperitoneum was
      the only (0.4%) major unpredictable complication; minor complications were also
      infrequent (4%). Using both clinical and laboratory data and US examination the
      physician misdiagnosed liver histology in 25% of cases. After LB the physicians
      changed their opinion on whether to treat with PEG-INF plus ribavirin in 43
      (15.5%) cases. Liver histology allows more accurate diagnosis and enables
      physicians to make the most appropriate choic.

PMID- 22475659
TI  - Social and demographic determinants in the prescription of systemic antibiotics.
AB  - Spain presents a high level of systemic antibiotic consumption and subsequently
      shows important rates of bacterial resistance. Diverse parameters explain the
      uneven distribution of their consumption such as the epidemiology of infectious
      processes, population-dependent factors, and factors dependent on the prescribing
      doctor. The aim of this study was to investigate demographic parameters that may
      affect antibiotic consumption. We carried out a retrospective longitudinal study
      from 2001 to 2005 on the basis of antibiotic consumption data provided by the
      information system of the drugstore Concylia. The consumption indicator used is
      the number of defined daily doses per 1000 inhabitants per day (DID). The area
      studied was the region of Castile and Leon, with nine provinces and eleven health
      districts. Global consumption per health district under study was as follows:
      Avila (22.37 DID), Zamora (21.83 DID), Salamanca (21.0 DID), Soria (20.67 DID),
      Palencia (18.97 DID), Leon (17.56 DID), Burgos (16.59 DID), Segovia (16.50 DID),
      East Valladolid (16.36 DID), The Bierzo (16 DID) and the lowest consumer, West
      Valladolid (13.46 DID). Different patterns of consumption were found in the study
      period, according to the variability of infectious diseases and demographic
      factors such as population age and population density. Significant area-dependent
      global consumption differences were observed in relation to acute respiratory
      infections and population-dependent factors. The differences were more marked
      when studying the geographical distribution of the consumption of the principal
      active ingredients.

PMID- 22475660
TI  - Use of direct renin inhibitor in an HIV positive subject.
AB  - OBJECTIVES: Drugs acting on the renin angiotensin system (RAS), such as
      angiotensin converting enzyme (ACE) inhibitors and sartans, have been used for
      hypertension treatment in the HIV-negative population. These drugs reduce
      hypertension related cardiovascular diseases such as renal impairment in the
      general population. Limited data show similar findings also in the HIV-positive
      population. A new drug called aliskiren has recently become available on the
      market: it is able to block the RAS by a different mechanism acting as direct
      renin inhibitor. No data are available about the use of aliskiren in HIV-positive
      patients. CASE REPORT: A 61-year-old HIV-infected Caucasian male (CDC C3) patient
      with hypertension for ten years and cardiovascular complications took carvedilol
      25 mg twice a day, plus daily administration of irbesartan 300 mg,
      hydroclorotiazide 25 mg, doxazosin 4 mg, lacidipine 6 mg, and simvastatin 40 mg.
      He took AZT+ 3TC + RAL with a good profile on HIV replication and immunological
      parameters. We found a non-optimal blood pressure value and decided to start
      aliskiren 150 mg a day to improve blood pressure control. After one month blood
      pressure control and proteinuria improved. In our case the use of low doses of
      aliskiren appeared to improve the level of blood pressure, although five
      antihypertensive agents had already been used on the patient. Finally, although
      aliskiren would appear to have no direct effect on viro-immunological parameters
      and does not seem to interfere with cART, further studies are warranted in this
      context.

PMID- 22475661
TI  - [Hepatitis: a longstanding companion in human history].
AB  - Hepatitis has gone along with human history since its origins, due to its prompt
      identifiability linked to jaundice as a symptom. Written evidence of outbreaks of
      epidemic jaundice can be tracked back a few millenniums before Christ. 
      Unavoidable confusion arises due to the overlap of different sources possibly
      linked to different aetiologies, identified over time as epidemic jaundice (HAV
      or HEV hepatitis?) and serum hepatitis (HBV or HCV hepatitis?). The journey that
      brought to recognize viruses as the main cause of jaundice was long and started
      midway during the last century, when the infectious hypothesis, which had taken
      place step by step, was finally confirmed by epidemiological investigations of an
      outbreak occurring in the US army in 1942, after a yellow fever immunization
      campaign.  Further research identified two clinically different types of
      hepatitis, called for the first time hepatitis A and hepatitis B.

PMID- 22475662
TI  - From miasmas to germs: a historical approach to theories of infectious disease
      transmission.
AB  - From miasma to germ theory we trace the evolution of conceptions in infectious
      disease transmission. Starting from the unproved theories of contagiousness we
      move on to miasma theory, contagion theory and spontaneous generation theory up
      to the revolutionary germ theory of disease transmission.

PMID- 22475663
TI  - [Long-term fever after gastric banding].
AB  - We report a 65-year-old male, suffering from aspiration pneumonia after gastric
      banding revealed by intermittent fever inducing a delayed diagnosis. Several
      early and later pulmonary complications following laparoscopic gastric banding
      have been reported. Removal or deflation of the band should be considered in
      unexplained persistent fever to avoid more severe complications such as
      respiratory distress.

PMID- 22475664
TI  - Cementum annulations, age estimation, and demographic dynamics in Mid-Holocene
      foragers of North India.
AB  - One of the principal problems facing palaeodemography is age estimation in adult
      skeletons and the centrist tendency that affects many age estimation methods by
      artificially increasing the proportion of individuals in the 30-45-year age
      category. Several recent publications have indicated that cementum annulations
      are significantly correlated with known age of extraction or death. This study
      addresses the question of how demographic dynamics are altered for an
      archaeological sample when cementum-based age estimates are used as opposed to
      those obtained via conventional macroscopic methods. Age pyramids were
      constructed and demographic profiles were compared for the early Holocene
      skeletal population from Damdama (India). The results demonstrate that the use of
      cementum annulations for age estimation in only a subset of the skeletal sample
      has a significant impact on the demographic profile with regard to specific
      parameters such as mean age at death and life expectancy at birth. This confirms
      the importance of using cementum annulations to refine age estimates in
      archaeological samples, which, when combined with a fertility-centred approach to
      demography, can provide new insights into population dynamics in the past.

PMID- 22475665
TI  - Commentary on "experience with pandemic 2009 H1N1 influenza in a large pediatric
      hospital".

PMID- 22475666
TI  - Educating medical students in evidence-based medicine:  what we should expect as
      a starting point for our house officers.

PMID- 22475667
TI  - HIV preexposure prophylaxis: walking ahead on tightropes.

PMID- 22475668
TI  - Experience with pandemic 2009 H1N1 influenza in a large pediatric hospital.
AB  - OBJECTIVE: In 2009, a new strain of influenza A, H1N1, was detected in two
      children in the United States. It spread quickly and became pandemic (pH1N1),
      disproportionately affecting children. The aim of the present study was to
      describe our experience with pH1N1 in a large pediatric hospital. METHODS: We
      reviewed the clinical records of all of the children diagnosed as having
      influenza A at Children's Hospital, New Orleans, LA, for the period April 2009 to
      May 2010. Diagnosis was made by rapid influenza test or direct fluorescent
      antibody. Specimens form hospitalized children were sent to the Louisiana Office
      of Public Health for confirmation by reverse-transcription-polymerase chain
      reaction. RESULTS: During the 14-month study period, 10,470 children were tested
      and 1463 (14%) tested positive for influenza A. Boys were more commonly infected
      than girls (53% vs 47%, P < .001). Of the cases, 1308 (89%) were ambulatory and
      155 (11%) were hospitalized. Hospitalized children were younger, more frequently
      white, had non-Medicaid insurance, and had comorbidity. Of the 155 admissions, 14
      (9%) were admitted to the intensive care unit. Having a comorbidity increased and
      being black decreased the chances of being admitted to the intensive care unit.
      Three children died, all with severe neurologic or respiratory predisposing
      illness. Eight cases of hospital-onset influenza and 6 of repeat infection were
      detected. CONCLUSIONS: pH1N1 burdened pediatric facilities during the 2009-2010
      influenza season. Even though most cases were mild and self-limited, some
      resulted in severe disease and long-term complications.

PMID- 22475669
TI  - Preexposure prophylaxis for HIV infection: healthcare providers' knowledge,
      perception, and willingness to adopt future implementation in the southern US.
AB  - BACKGROUND: Understanding providers' perspective on preexposure prophylaxis
      (PrEP) would facilitate planning for future implementation. METHODS: A survey of
      care providers from sexually transmitted disease and family planning clinics in
      South Carolina and Mississippi was conducted to assess their knowledge,
      perception, and willingness to adopt PrEP. Multivariable logistic and general
      linear regression with inverse propensity score treatment weights were used for
      analyses. RESULTS: Survey response rate was 360/480 (75%). Median age was 46.9
      years and a majority were women (279 [78%]), non-Hispanic white (277 [78%]),
      nonphysicians (254 [71%]), and public health care providers (223 [62%]).
      Knowledge about PrEP was higher among physicians compared with nonphysicians (P =
      0.001); nonpublic health care providers compared with public health care
      providers (P = 0.023), and non-Hispanic whites compared with non-Hispanic blacks
      (P = 0.034). The majority of the providers were concerned about the safety,
      efficacy, and cost of PrEP. Providers' perceptions about PrEP were significantly
      associated with their sociodemographic and occupational characteristics. The
      willingness to prescribe PrEP was more likely with higher PrEP knowledge scores
      (adjusted odds ratio [aOR] 14.94; 95% confidence interval [CI] 3.21-69.61), older
      age (aOR 1.14; 95% CI 1.01-1.29), and in those who agreed that "PrEP would
      empower women" (aOR 2.90; 95% CI 1.28-6.61); and was less likely for "other"
      race/ethnicity versus white (aOR 0.23; 95% CI 0.07-0.76) and in those who agreed
      that "PrEP, if not effective, could lead to higher HIV transmission" (aOR 0.45;
      95% CI 0.27-0.75). CONCLUSIONS: To improve the acceptance of PrEP among
      providers, there is a need to develop tailored education/training programs to
      alleviate their concerns about the safety and efficacy of PrEP.

PMID- 22475670
TI  - Orthopedic surgery postgraduate year 1 intern curriculum improves initial
      orthopedic in-training examination performance.
AB  - OBJECTIVE: To determine the efficacy of an educational curriculum designed for
      orthopedic surgery postgraduate year 1 (PGY-1) interns to improve initial
      Orthopedic In-Training Examination (OITE) performance. METHODS: A retrospective
      cohort study was performed that evaluated the PGY-1 intern OITE performance of
      one residency training program (n = 55) during 7-year periods before (1996-2002)
      and after structured curriculum implementation (2003-2009). RESULTS: Linear
      regression analysis revealed insignificant changes in median PGY-1 intern OITE
      percentile rank during the precurriculum period (R = 0.08, P = 0.53).
      Postcurriculum period comparisons revealed significantly improving PGY-1 intern
      OITE percentile rank (R = 0.46, P = 0.048). Pre- and postcurriculum median US
      Medical Licensing Examination (USMLE) Step I scores did not display statistically
      significant differences (218.2 +/- 6.6 vs 229.1 +/- 13.8, Mann-Whitney U test, z
      = -1.5, P = 0.10). Spearman rho correlations revealed a moderate relation (r =
      0.61) between postcurriculum PGY-1 intern OITE percentile rank and USMLE Step I
      score, but not during the precurriculum period. A moderate relation (r = 0.50)
      also was observed between postcurriculum USMLE Step I score and average OITE
      percentile rank during the 5-year residency program, but not during the
      precurriculum period. CONCLUSIONS: PGY-1 intern OITE percentile rank improved
      significantly with the addition of a specially designed educational curriculum.
      The stronger USMLE Step I score and PGY-1 intern OITE percentile rank relation
      observed during the postcurriculum period suggests that interns who participated
      in the educational curriculum were better prepared to translate general medical
      and patient care knowledge into orthopedic surgery knowledge.

PMID- 22475671
TI  - Intimate partner violence education for medical students:  toward a comprehensive
      curriculum revision.
AB  - OBJECTIVES: Previous studies examined the prevalence and efficacy of intimate
      partner violence (IPV) education in medical school. We documented IPV content
      exposure shortage in medical school curriculum at a southern university health
      science center and measured personal IPV experience among medical students.
      METHODS: Responses were gathered from a 67-item survey adapted from the Physician
      Readiness to Manage Intimate Partner Violence Survey. Our survey measured IPV
      knowledge and attitudes, along with sufficiency of IPV education that students
      received before and during medical school. Three summary scales were created to
      examine students' perceived preparedness to deal with IPV survivors and their
      perceived and actual knowledge about IPV. RESULTS: Across summary scales,
      differences were higher but not significant between medical students who received
      IPV education either before or during medical school and those with no IPV
      education. Of all of the medical students surveyed, 28.7% (n = 33) had
      experienced some type of domestic violence including IPV. Gaps in knowledge also
      were identified. CONCLUSIONS: Student IPV experience (whether directly by way of
      personal exposure to IPV or indirectly through family members or acquaintances
      who were victims of IPV) can be applicable in classrooms, clinics, and students'
      careers, but it may not necessarily increase perceived or actual IPV knowledge;
      however, our results show that any IPV education that students receive can be
      effective in increasing confidence and perceived preparedness to address IPV with
      patients. Comprehensive approaches to teaching IPV should be integrated fully
      into medical school curricula.

PMID- 22475672
TI  - Commentary on "intimate partner violence education for medical students:  toward
      a comprehensive curriculum revision".

PMID- 22475673
TI  - Universal newborn screening:  knowledge, attitudes, and satisfaction among public
      health professionals.
AB  - OBJECTIVE: Assess knowledge, attitude, and satisfaction with the newborn
      screening (NBS) system among pediatric public health leaders in the state of
      Florida. METHODS: Online surveys and open-ended telephone interviews were
      administered to 10 county medical directors for a state-funded program that
      oversees NBS. Survey questions examined basic knowledge regarding NBS, views on
      provider and parent access to NBS information, and recommendations for improving
      the information distribution system. RESULTS: Providers learn about NBS from the
      American Academy of Pediatrics, the Department of Health, and continuing medical
      education; however, 80% of providers were concerned about receiving inadequate
      information. Thirty percent of the providers surveyed reported that it takes >14
      days to receive NBS results. The majority (80%) were concerned that parents may
      not receive adequate information about their infant's condition, treatment, or
      prognosis. No provider reported being confident in his or her ability to assess
      how well a parent understands a positive NBS result. Eighty percent of those
      surveyed believe that the pediatric primary care provider is responsible for
      providing NBS information to parents and almost all of the providers (90%)
      believed parents should be notified of normal NBS results. CONCLUSIONS: This
      study indicates dissatisfaction with and confusion about NBS. Addressing this
      problem requires action at the levels of medical education, clinical care, health
      policy, and information systems.

PMID- 22475674
TI  - Commentary on "universal newborn screening: knowledge, attitudes, and
      satisfaction among public health professionals".

PMID- 22475675
TI  - Disparities in firearms ownership and storage practices in North Carolina.
AB  - OBJECTIVE: Because household firearms pose a risk to children, this study
      examined firearms accessibility in North Carolina households with children.
      METHODS: In 2008, parents completing the North Carolina Child Health Assessment
      and Monitoring Program survey were asked how many firearms they owned and their
      firearms storage practices. Weighted analyses provided estimates of ownership and
      storage practices and examined variation by sociodemographics. RESULTS: A total
      of 37% of 2885 parents reported owning firearms. Whites (adjusted odds ratio
      [aOR] 3.9 [95% confidence interval {CI} 2.9-5.2]), households with income >200%
      of the federal poverty level (aOR 1.7 [95% CI 1.2-2.5]) and married parents (aOR
      2.4 [95% CI 1.8-3.4]) were more likely to own firearms. Ownership of more than
      one firearm was greater among whites (aOR 2.2 [95% CI 1.4-3.4]) and married
      parents (aOR 1.8 [95% CI 1.5-2.8]) than other groups. The number of firearms
      owned increased with children's age. Although most parents reported keeping
      firearms locked and unloaded (57%), many reported unsafe storage practices, which
      varied by race/ethnicity. Whites were more likely (45%) to store firearms
      unlocked and/or loaded than other groups (35%). CONCLUSIONS: Many North Carolina
      youth have access to household firearms, with white youth being more likely to
      have firearms, a greater number of firearms, and less safely stored firearms than
      other race/ethnicity groups. Further interventions and policies to reduce youth
      access to household firearms are needed. Future research should examine and
      address why whites, married couples, and those with socioeconomic advantages are
      more likely than individuals not belonging to these groups to own household
      firearms and store them unsafely.

PMID- 22475676
TI  - Calcium abnormalities in hospitalized patients.
AB  - Depending upon the method of measurement, hypocalcemia occurs in 15% to 88% and
      hypercalcemia occurs in 15% of hospitalized patients. Ionized calcium should be
      measured in place of total serum calcium to avoid errors related to
      hypoalbuminemia, which is seen commonly in acutely ill patients. Symptomatic
      hypocalcemia requires prompt intravenous calcium administration. Symptomatic
      hypercalcemia (most often caused by hyperparathyroidism or malignancy) warrants
      aggressive intravenous hydration to correct volume depletion and, usually,
      additional therapy with diuretics, bisphosphonates, calcitonin, or
      corticosteroids. Identification and treatment of the underlying cause of the
      calcium derangement must be addressed after the acute electrolyte abnormality is
      stabilized.

PMID- 22475677
TI  - Patient opinion regarding patient-centered medical home fundamentals.
AB  - OBJECTIVES: Although conceptually there is agreement on how the Patient-Centered
      Medical Home (PCMH) should be organized, there is little information regarding
      which PCMH components are the most important to patients. METHODS: An anonymous,
      voluntary survey was administered to patients at three US academic medical
      centers. Questions sought opinions regarding the National Committee for Quality
      Assurance's key components and essential elements of the PCMH. Analysis of the
      survey responses was conducted using SAS version 9.1. RESULTS: A total of 780
      surveys were returned. Patients expressed believing strongly that the ability to
      coordinate care, help patients to manage their own disease, and track laboratory
      results were the most important aspects of a PCMH office. There were no
      differences in response to the survey according to age, sex, race, or site.
      Patients listed care coordination, patient self-management, and improved access
      to care as the top priority attributes of a PCMH. CONCLUSIONS: Patients were
      consistent in their opinions that care coordination, access, and patient self
      management were the most important elements of a PCMH.

PMID- 22475678
TI  - Mitotic chromosome condensation in vertebrates.
AB  - Work from several laboratories over the past 10-15 years has revealed that,
      within the interphase nucleus, chromosomes are organized into spatially distinct
      territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture
      and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T.
      Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome
      territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307
      316]. The overall compaction level and intranuclear location varies as a function
      of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle,
      P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology
      of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and
      specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock,
      W.A. Bickmore, Spatial organization of active and inactive genes and noncoding
      DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A,
      A'). In prophase, when cyclin B activity reaches a high threshold, chromosome
      condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this
      point vertebrate chromosomes appear as compact structures harboring an attachment
      point for the spindle microtubules physically recognizable as a primary
      constriction where the two sister chromatids are held together. The transition
      from an unshaped interphase chromosome to the highly structured mitotic
      chromosome (compare Figs. 1A and B) has fascinated researchers for several
      decades now; however a definite picture of how this process is achieved and
      regulated is not yet in our hands and it will require more investigation to
      comprehend the complete process. From a biochemical point of view a vertebrate
      mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone
      proteins (40%) [6]. I will discuss below what is known to date on the
      contribution of these two different classes of proteins and their co-operation in
      establishing the final mitotic chromosome structure.

PMID- 22475679
TI  - Cost and cost effectiveness of long-lasting insecticide-treated bed nets - a
      model-based analysis.
AB  - BACKGROUND: The World Health Organization recommends that national malaria
      programmes universally distribute long-lasting insecticide-treated bed nets
      (LLINs). LLINs provide effective insecticide protection for at least three years
      while conventional nets must be retreated every 6-12 months. LLINs may also
      promise longer physical durability (lifespan), but at a higher unit price. No
      prospective data currently available is sufficient to calculate the comparative
      cost effectiveness of different net types. We thus constructed a model to explore
      the cost effectiveness of LLINs, asking how a longer lifespan affects the
      relative cost effectiveness of nets, and if, when and why LLINs might be
      preferred to conventional insecticide-treated nets. An innovation of our model is
      that we also considered the replenishment need i.e. loss of nets over time.
      METHODS: We modelled the choice of net over a 10-year period to facilitate the
      comparison of nets with different lifespan (and/or price) and replenishment need
      over time. Our base case represents a large-scale programme which achieves high
      coverage and usage throughout the population by distributing either LLINs or
      conventional nets through existing health services, and retreats a large
      proportion of conventional nets regularly at low cost. We identified the
      determinants of bed net programme cost effectiveness and parameter values for
      usage rate, delivery and retreatment cost from the literature. One-way
      sensitivity analysis was conducted to explicitly compare the differential effect
      of changing parameters such as price, lifespan, usage and replenishment need.
      RESULTS: If conventional and long-lasting bed nets have the same physical
      lifespan (3 years), LLINs are more cost effective unless they are priced at more
      than USD 1.5 above the price of conventional nets. Because a longer lifespan
      brings delivery cost savings, each one year increase in lifespan can be
      accompanied by a USD 1 or more increase in price without the cheaper net (of the
      same type) becoming more cost effective. Distributing replenishment nets each
      year in addition to the replacement of all nets every 3-4 years increases the
      number of under-5 deaths averted by 5-14% at a cost of USD 17-25 per additional
      person protected per annum or USD 1080-1610 per additional under-5 death averted.
      CONCLUSIONS: Our results support the World Health Organization recommendation to
      distribute only LLINs, while giving guidance on the price thresholds above which
      this recommendation will no longer hold. Programme planners should be willing to
      pay a premium for nets which have a longer physical lifespan, and if planners are
      willing to pay USD 1600 per under-5 death averted, investing in replenishment is
      cost effective.

PMID- 22475680
TI  - Recapitulation of genome-wide association studies on pulse pressure and mean
      arterial pressure in the Korean population.
AB  - Increased pulse pressure (PP) and decreased mean arterial pressure (MAP) are
      strong prognostic predictors of adverse cardiovascular events. Recently, the
      International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP
      GWAS) reported eight loci that influenced PP and MAP. The ICBP-GWAS examined 51
      cohorts--comprising 122 671 individuals of European ancestry--and identified
      eight SNPs: five that governed PP and three that controlled MAP. Six of these
      loci were novel. To replicate these newly identified loci and examine genetic
      architecture of PP and MAP between European and Asian populations, we conducted a
      meta-analysis of the eight SNPs combining data from ICBP and general population
      based Korean cohorts. Two SNPs (rs13002573 (FIGN) and rs871606 (CHIC2)) for PP
      and two SNPs (rs1446468 (FIGN) and rs319690 (MAP4)) for MAP were replicated in
      Koreans. Although our GWAS only found moderate association, we believe that the
      findings promote us to propose that a similar genetic architecture governs PP and
      MAP in Asians and Europeans. However, further studies will be needed to confirm
      the possibility using other Asian population.

PMID- 22475681
TI  - Deracemization of secondary alcohols by chemo-enzymatic sequence with plant
      cells.
AB  - A screening based on undifferentiated plant cells allowed identifying Gardenia
      jasminoides as the best biocatalyst to perform the kinetic resolution of 1
      phenylethanol. This species was further tested for its ability to oxidize
      stereoselectively the (S)-isomers from racemic mixtures of secondary alcohols
      leaving their antipodes unaffected in Tris-HCl buffer. Those substrates which
      afforded the best results in the kinetic resolution were subjected to a chemo
      enzymatic sequence of deracemization. G. jasminoides immobilized cells in calcium
      alginate were used for the oxidation of the (S)-enantiomers and, in a second
      step, NaBH(4) was added to the same vessel for the reduction of the corresponding
      ketone. The sequential repetition of these two steps allowed obtaining the R
      alcohols in 82-90% yield in high optical purity (71-96% ee). Despite the
      viability of the cells is affected by the chemical reagent, their enzymes remain
      active due to the protective environment of the calcium alginate beads.

PMID- 22475683
TI  - Electronic and optical properties of Cu, CuO and Cu2O studied by electron
      spectroscopy.
AB  - The electronic and optical properties of Cu, CuO and Cu(2)O were studied by x-ray
      photoelectron spectroscopy (XPS) and reflection electron energy-loss spectroscopy
      (REELS). We report detailed Cu 2p, Cu LVV, O 1s and O KLL spectra which are in
      good agreement with previous results. REELS spectra, recorded for primary
      energies in the range from 150 to 2000 eV, were corrected for multiple
      inelastically scattered electrons to determine the effective inelastic scattering
      cross section. The dielectric functions and optical properties were determined by
      comparing the experimental inelastic electron scattering cross section with a
      simulated cross section calculated within the semi-classical dielectric response
      model in which the only input is Im(-1/epsilon) by using the QUEELS
      epsilon(k,omega)-REELS software package. By Kramers-Kronig transformation of the
      determined Im(-1/epsilon), the real and imaginary parts (epsilon(1) and
      epsilon(2)) of the dielectric function, and the refractive index n and extinction
      coefficient k were determined for Cu, CuO, and Cu(2)O in the 0-100 eV energy
      range. Observed differences between Cu, CuO and Cu(2)O are mainly due to
      modifications of the 3d and O 2p electron configurations.

PMID- 22475682
TI  - Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and
      metastasis of pancreatic cancer cells in vitro and in vivo through altering cell
      metabolism.
AB  - Pancreatic tumors are resistant to conventional chemotherapies. The present study
      was aimed at evaluating the potential of a novel plant-derived product as a
      therapeutic agent for pancreatic cancer (PC). The effects of an extract from the
      tropical tree Annona Muricata, commonly known as Graviola, was evaluated for
      cytotoxicity, cell metabolism, cancer-associated protein/gene expression,
      tumorigenicity, and metastatic properties of PC cells. Our experiments revealed
      that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The
      expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF
      1alpha, NF-kappaB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the
      presence of the extract. In vitro functional assays further confirmed the
      inhibition of tumorigenic properties of PC cells. Overall, the compounds that are
      naturally present in a Graviola extract inhibited multiple signaling pathways
      that regulate metabolism, cell cycle, survival, and metastatic properties in PC
      cells. Collectively, alterations in these parameters led to a decrease in
      tumorigenicity and metastasis of orthotopically implanted pancreatic tumors,
      indicating promising characteristics of the natural product against this lethal
      disease.

PMID- 22475684
TI  - Drug interactions with oral antidiabetic agents: pharmacokinetic mechanisms and
      clinical implications.
AB  - There is a growing epidemic of type 2 diabetes (T2DM), and it is associated with
      various comorbidities. Patients with T2DM are usually treated with multiple
      drugs, and are therefore at an increased risk of harmful drug-drug interactions
      (DDIs). Several potentially life-threatening DDIs concerning oral antidiabetic
      drugs have been identified. This has mostly been initiated by case reports but,
      more recently, the understanding of their mechanisms has greatly increased. In
      this article, we review the pharmacokinetic DDIs concerning oral antidiabetics,
      including metformin, sulfonylureas, meglitinide analogs, thiazolidinediones and
      dipeptidyl peptidase-4 inhibitors, and the underlying mechanistic basis that can
      help to predict and prevent DDIs. In particular, the roles of membrane
      transporters and cytochrome P450 (CYP) enzymes in these DDIs are discussed.

PMID- 22475685
TI  - How patients evaluate breast reconstruction after mastectomy, and why their
      evaluation often differs from that of their clinicians.
AB  - INTRODUCTION: The evaluation of breast reconstruction after treatment for cancer
      sometimes differs between the patient who receives it and the surgeon who
      performs it. Questionnaire studies shed little light on this. We therefore aimed
      to discover what factors influence how patients evaluate breast reconstruction
      and thereby to understand sources of disagreement between practitioners and
      patients in their evaluation. METHODS: At the study centre, patients who undergo
      reconstruction following breast cancer rate their subjective evaluation of the
      procedure, and the surgeon and breast care nurse jointly rate their assessment of
      cosmesis. We interviewed in depth 27 patients with a range of scores on each
      rating to elicit the reasons for their evaluations. Interviews were analysed
      qualitatively with particular attention to patients whose evaluations diverged
      from those of practitioners. RESULTS: Influences on patients' subjective
      evaluations included two aspects of cosmesis (how 'normal' they felt and how
      normal or attractive they thought they appeared to others), but also how much
      they trusted and respected their practitioners and felt cared for by them,
      whether reconstruction had helped to complete their 'cancer journey' and post
      operative complications. CONCLUSION: Patients' subjective evaluation of
      reconstruction after cancer treatment extends well beyond cosmesis, and
      experience of cancer influences what they consider important. Evaluations
      therefore often differ from those of practitioners. Surgeons and specialist
      nurses need to be aware of the factors that influence patients' evaluations in
      order to guide patients appropriately in decisions about surgery, and to evaluate
      outcomes across the domains that matter to patients.

PMID- 22475686
TI  - The pedicled masseter muscle transfer for smile reconstruction in facial
      paralysis: repositioning the origin and insertion.
AB  - BACKGROUND: The pedicled masseter muscle transfer (PMMT) is introduced as a new
      reconstructive option for dynamic smile restoration in patients with facial
      paralysis. The masseter muscle is detached from both its origin and insertion and
      transferred to a new position to imitate the function of the native zygomaticus
      major muscle. METHODS: Part one of this study consisted of cadaveric dissections
      of 4 heads (eight sides) in order to determine whether the masseter muscle could
      be (a) pedicled solely by its dominant neurovascular bundle and (b) repositioned
      directly over the native zygomaticus major. The second part of the study
      consisted of clinical assessments in three patients in order to confirm the
      applicability of this muscle transfer. Commissure excursion and vector of
      contraction following PMMT were compared to the non-paralyzed side. RESULTS: In
      all eight sides, the masseter muscles were successfully isolated on their pedicle
      and transposed on top of and in-line with the ipsilateral zygomaticus major. The
      mean length of the masseter and its angle from Frankfurt's horizontal line after
      transposition compared favorably to the native zygomaticus major muscle. In the
      clinical cases, the mean commissure movements of the paralyzed and normal sides
      were 7 mm and 12 mm respectively. The mean angles of commissural movement for the
      paralyzed and normal sides were 62 degrees  and 59 degrees  respectively.
      CONCLUSIONS: The PMMT can be used as a dynamic reconstruction for patients with
      permanent facial paralysis. As we gain experience with the PMMT, it may be
      possible to use it as a first-line option for patients not eligible for free
      micro-neurovascular reconstruction.

PMID- 22475687
TI  - A simple and direct procedure for excision of peripheral skin above the nail root
      to enable nail lengthening after fingertip amputation.

PMID- 22475689
TI  - Change of the initiation time of blood coagulation in pregnancy from 10-months to
      postpartum.
AB  - We measured the time of initiation of blood coagulation (Ti) from pregnancy 10
      months (36~40 weeks) till 1-month after delivery, paying particular attention to
      the very early postpartum period, using a damped oscillation rheometer that is
      approximately 160 times more sensitive than the Thromboelastogram(r) to evaluate
      the risk of thrombus formation. Blood samples were obtained from healthy
      volunteers at pregnancy 10-month, 1-hour, 3-hours, 4-days, 7-days, 3-weeks and 1
      month after delivery. Ti values at pregnancy 10-month, 1-hour, 3-hours, 4-days, 7
      days, 3-weeks, 1-month after delivery and in non-pregnant females were 20.4 +/-
      2.2, 11.7 +/- 1.6, 13.2 +/- 3.1, 17.2 +/- 2.0, 20.2 +/- 1.6, 21.4 +/- 4.0, 24.6
      +/- 3.6, and (25.0 +/- 3.4) minutes, respectively. Ti was significantly shorter
      at pregnancy 10-month, 1-hour, 3-ours, 4-days, 7-days and 3-weeks after delivery
      than in non-pregnant females. These data show that the blood of pregnant females
      is more hypercoagulable than non-pregnant females from pregnancy 10-month until 3
      weeks post delivery, suggesting that they are at high risk of VTE after discharge
      from hospital.

PMID- 22475688
TI  - EGFR protein overexpression correlates with chromosome 7 polysomy and poor
      prognostic parameters in clear cell renal cell carcinoma.
AB  - BACKGROUND: The role of epidermal growth factor (EGF) and its receptor (EGFR) in
      the pathogenesis and progression of various malignant tumors has long been known,
      but there is still disagreement concerning prognostic significance of EGFR
      expression in clear cell renal cell carcinoma (CCRCC). The present study was
      designed to analyze more objectively the protein EGFR expression in CCRCC and to
      compare its value with EGFR gene copy number changes and clinicopathologic
      characteristics including patient survival. METHODS: The protein EGFR expression
      was analyzed immunohistochemically on 94 CCRCC, and gene copy number alterations
      of EGFR by FISH analysis on 41 CCRCC selected according to distinct membrane EGFR
      staining. RESULTS: Membrane EGFR expression in tumor cells was heterogeneous with
      respect to the proportion of positive cells and staining intensity. FISH analysis
      did not reveal EGFR gene amplification, while polysomy of chromosome 7 found in
      41% was associated with higher EGFR membrane expression. Moreover, EGFR
      overexpression was associated with a higher nuclear grade, larger tumor size and
      shorter patient's survival, while there was no connection with pathological
      stage. CONCLUSION: In conclusion, the protein expression of EGFR had an impact on
      prognosis in patients with CCRCC, while an increased copy number of chromosome 7
      could be the possible reason for EGFR protein overexpression in the absence of
      gene amplification.

PMID- 22475690
TI  - [Consensus on the clinical impact of the new scientific evidence available on
      benign prostatic hyperplasia].
AB  - OBJECTIVES: To study the technical opinion of an expert panel and reach a
      consensus of professional criterion in relation to the most recent scientific
      evidence in Benign Prostatic Hyperplasia (BPH) in the scopes of diagnosis,
      progression criteria, medical treatment and surgical treatment. MATERIAL AND
      METHODS: Systematized review of the literature of the last 10 years in BPH by
      means of a scientific committee and elaboration of a 64-question questionnaire
      divided into three strategic areas: 1.- Diagnosis and stratification of the
      patients with BPH considering the progression risk factors. 2.-Novelties in the
      medical treatment and 3.- New contributions in the surgical and minimally
      invasive treatment in BPH. A panel of 50 urologists standing out for their
      knowledge in BPH distributed throughout the national geographic area was chosen,
      establishing the Delphi methodology for the study through the application of two
      successive online surveys. RESULTS: The 50 experts consulted completed the two
      groups of the questionnaire. In the first, a consensus of criterion was observed
      in 50 out of the 64 questions analyzed, achieving a consensus in 59/65 (92.5%) in
      the second round, which included aspects of morbidity of the lower urinary tract
      symptoms (LUTS), diagnostic tests necessary in the initial evaluation of the
      specialist, stratification of the patients in relation to the risk of
      progression, strategies of step-by-step medical therapy and combination in
      patients with risk of Acute Urinary Retention (AUR) or surgery and of the
      indications of surgical therapy and the role of new less invasive treatments.
      CONCLUSIONS: In a condition of the high prevalence of BPH, in which we have seen
      important changes in its entire spectrum in recent years, the obtaining of an
      elevated consensus to which a large number of reference specialists in this
      condition have contributed will be of great importance for the usual clinical
      management of this disease.

PMID- 22475691
TI  - [Experience of open renal trauma in a urology service].
AB  - INTRODUCTION: Opened renal trauma in urban areas reaches 15 to 20% of all renal
      traumas. It is mainly caused by gunshot wounds or knifes. Gunshot wounds are
      classified as high energy trauma and are usually associated to other organ
      injuries. We present our experience in opened renal trauma in the last 24 months.
      MATERIAL AND METHODS: Retrospective study: patients with thoracic, abdominal and
      thoraco-abdominal trauma admitted to the emergency room between July 2009 and
      June 2011 were studied. Fourteen patients were identified with opened renal
      trauma, with diagnostic confirmation by imaging study or during surgery. RESULTS:
      Ages ranged from 16 to 37 years, with a mean age of 24.5 years. Thirteen patients
      were males. The mechanism of injury was produced by gunshot in 71% (10/14) and by
      knife in 29% (4/14). The opened renal traumas were classified according to the
      American Association for the Surgery of Trauma. Of these, 3/14 (21%) belonged to
      grade II, 4/14 (29%) to grade III, 4/14 (29%) to grade IV and 3/14 to grade V
      (21%). Fall in hematocrit ranged from 1% to 27%, with an average of 13.9%.
      Expectant management was done in six patients, however, this management did not
      take into account those surgeries performed due to non-urologic organ injuries.
      Six patients (42%) required nephrectomy. Thoraco-abdominal injuries were
      associated in 11 patients (79%). CONCLUSIONS: Despite the low incidence of opened
      renal trauma, many patients are observed when other national reports are
      considered, probably due to the socio-cultural characteristics of this hospital.

PMID- 22475692
TI  - Songbird chemosignals: volatile compounds in preen gland secretions vary among
      individuals, sexes, and populations.
AB  - Chemical signaling has been documented in many animals, but its potential
      importance in avian species, particularly songbirds, has received far less
      attention. We tested whether volatile compounds in the preen oil of a songbird
      (Junco hyemalis) contain reliable information about individual identity, sex, or
      population of origin by repeated sampling from captive male and female juncos
      originating from 2 recently diverged junco populations in southern California.
      One of the populations recently colonized an urban environment; the other resides
      in a species-typical montane environment. The birds were field-caught as
      juveniles, housed under identical conditions, and fed the same diet for 10 months
      prior to sampling. We used capillary gas chromatography-mass spectrometry to
      quantify the relative abundance of 19 volatile compounds previously shown to vary
      seasonally in this species. We found individual repeatability as well as
      significant sex and population differences in volatile profiles. The persistence
      of population differences in a common environment suggests that preen oil
      chemistry likely has a genetic basis and may thus evolve rapidly in response to
      environmental change. These finding suggest that songbird preen oil odors have
      the potential to function as chemosignals associated with mate recognition or
      reproductive isolation.

PMID- 22475693
TI  - Spontaneous echo contrast in internal jugular veins: a probable indicator for
      systemic inflammation and a prothrombotic state.
AB  - The hypothesis that spontaneous echo contrast (SEC) in the internal jugular vein
      (IJV) is a clinical indicator for systemic inflammation and thrombogenesis is
      investigated in this study. Fifty-two patients with cardiovascular diseases and
      25 nondiseased subjects were evaluated. SEC was observed in 96 of 154 IJVs. The
      visual grading of SEC showed good interobserver agreement on SEC grades (kappa
      value: 0.846, p < 0.001). Generalized estimating equations analysis was used for
      univariate and multivariate analysis. Univariate analysis showed that peak flow
      velocity in corresponding IJV (coefficient -0.001 [95% CI -0.019, -0.001], p =
      0.031), jugular venous reflux (JVR, -0.010 [-0.019, -0.001], p = 0.002), plasma
      levels of fibrinogen (0.464 [0.208, 0.719], p < 0.001) and hs-C-reactive protein
      (hs-CRP) (0.479 [0.184, 0.774], p = 0.001) and previous history of ischemic
      stroke (0.779 [0.139, 1.417]; p = 0.017) correlated with the grades of SEC in
      IJV. Increased plasma levels of fibrinogen and hs-CRP, previous ischemic stroke,
      lower peak velocity in corresponding IJV and JVR were also independent predictors
      for the higher grades of SEC in IJV in multivariate regression analysis. SEC in
      IJV could be evaluated easily and semiquantitatively. SEC in IJVs could be a
      putative marker of cerebral circulation disturbance and an indicator of systemic
      inflammatory or prothrombotic state.

PMID- 22475694
TI  - The role of preterm placental calcification in high-risk pregnancy as a predictor
      of poor uteroplacental blood flow and adverse pregnancy outcome.
AB  - This prospective cohort study aims to clarify the role of preterm placental
      calcification in high-risk (i.e., hypertension, diabetes, placenta previa or
      severe anemia) pregnant women as a predictor of poor uteroplacental blood flow
      (absent or reverse end-diastolic velocity [AREDV]) and adverse pregnancy outcome.
      Monthly ultrasound was performed starting at 28 weeks' gestation to establish the
      diagnosis of Grade III placental calcification, with measurement of Doppler
      velocimetry in the umbilical vessels at 32 weeks' gestation. The participants
      were classified into three groups: Group A (n = 776), a low-risk group without
      antenatal complication; group B (n = 42), a high-risk group with preterm (28 to
      36 weeks) placental calcification; and group C (n = 71), a high-risk control
      group without preterm (<36 weeks) placental calcification. Analyzed by logistic
      regression, the risks of AREDV (OR 4.32, 95%CI 1.25 to 14.94), adverse maternal
      outcome including postpartum hemorrhage (OR 3.98, 95% CI 1.20 to 13.20),
      placental abruption (OR 4.80, 95% CI 1.19 to 19.35), maternal transfer to
      intensive care unit (OR 3.83, 95% CI 1.10 to 13.33) and adverse fetal outcome
      including preterm birth (OR 3.86, 95% CI 1.32 to 11.29), low birth weight (OR
      2.99, 95% CI 1.11 to 8.03), low Apgar score (OR 5.14, 95% CI 1.64 to 16.08) and
      neonatal death (OR 4.52, 95% CI 1.15 to 17.73) were greater in group B compared
      with group C. In contrast, the risks of AREDV and adverse pregnancy outcome were
      significantly lower in group A than those in group C, except postpartum
      hemorrhage (OR 0.53, 95% CI 0.19 to 1.46). We conclude that in high-risk pregnant
      women, the presence of preterm placental calcification is a predictor of poor
      uteroplacental flow and adverse pregnancy outcome, requiring closer surveillance
      for maternal and fetal well-being. This finding helps identify the most dangerous
      population among high-risk pregnant women.

PMID- 22475695
TI  - Ultrasound safety with midfrequency transcranial sonothrombolysis: preliminary
      study on normal macaca monkey brain.
AB  - We investigated the safety of transcranial-targeting midfrequency (0.1 to 1 MHz)
      ultrasonic thrombolysis for acute ischemic stroke. We applied a new therapeutic
      and imaging transducer to healthy Macaca monkey brains via sonication of the
      ipsilateral middle cerebral artery through an acoustic temporal window. Young
      adult cynomolgus monkeys (Macaca fascicularis) were assigned to a group without
      sonication (control), a group maintained for 1 d after sonication (C1) and a
      group maintained for 7 d after sonication (C7; n = 3 for each). Two elder rhesus
      monkeys (Macaca mulatta) were ultrasonicated under transvenous injection of the
      recombinant tissue plasminogen activator alteplase (0.9 mg/kg), and maintained
      for 7 d (R). An automatic switching circuit alternately operated a therapeutic
      ultrasound beam (T-beam) generator for thrombolysis (frequency = 490 kHz;
      intensity = 0.72 W/cm(2)) and a diagnostic color-flow imaging ultrasound beam (D
      beam; frequency = 2.5 MHz; intensity = 0.20 W/cm(2)). A 15-min protocol,
      comprising four repeats of a sequence of 120-s T-beam activation followed by 30-s
      D-beam activation and then 5-min T-beam deactivation together with D-beam
      activation, was repeated four times over 60 min. After confirmation of neurologic
      deficits, the brains were removed and investigated histologically and
      immunohistochemically. Three skull samples were subjected to 494-kHz continuous
      waveform ultrasound, the transcranial intensity was measured and the mechanical
      index was calculated. None of the monkeys showed neurologic deficits after
      ultrasonication. The transskull ultrasound intensity rate was 48 +/- 12%. The
      intracranial mechanical index value was 0.15. The novel system did not cause
      tissue damage in the primate brain and no cavitation effect was detected
      intracranially.

PMID- 22475696
TI  - Correlation and agreement between contrast-enhanced ultrasonography and perfusion
      computed tomography for assessment of liver metastases from endocrine tumors:
      normalization enhances correlation.
AB  - We studied correlation and agreement between perfusion parameters derived from
      contrast-enhanced ultrasonography (CEUS) and computed tomography (CT). Both
      techniques were performed in 16 patients with proven liver metastases from
      endocrine tumor. Replenishment study after ultrasound-induced destruction of
      microbubbles was used for CEUS quantification. CEUS-derived relative values of
      blood flow, blood volume and mean transit time were compared with perfusion CT
      derived parameters measured in the same tumors. Significant correlation was
      observed between CEUS normalized values and CT absolute tumor values for blood
      flow (r = 0.58; p = 0.018), blood volume (r = 0.61; p = 0.012) and mean transit
      time (r = 0.52; p = 0.037). Correlation was not significant for non-normalized
      values. Agreement between CEUS normalized values and perfusion CT relative values
      was significant (p < 0.04). Estimated bias between CEUS and CT for relative
      perfusion values was -1.38 (-5.02; 2.27) for blood flow, +0.26 (-0.79; 1.31) for
      blood volume and +0.21 (-0.46; 0.87) for mean transit time. We conclude that
      normalization markedly increased correlation between CEUS- and CT-derived
      perfusion values and allowed agreement assessment.

PMID- 22475697
TI  - The influence of gas saturation on microbubble stability.
AB  - Accurate acoustic characterisation is an essential component of any experimental
      investigation concerning the use and development of microbubble contrast agents.
      It is of increasing importance as applications such as therapy and molecular and
      quantitative imaging are investigated. Such characterisation is generally
      conducted in the laboratory in the form of bulk acoustic studies or optical
      observation of single bubbles using high speed photography in a water tank
      containing "out-gassed" water. The approach is widely used in acoustics to
      prevent inaccurate measurements being made due to the presence of gas bubbles
      settling on instrumentation, however, the term is often used to cover a range of
      water preparation techniques and the final gas content of the water is not
      usually stated. This technical note demonstrates the influence of gas content on
      the stability of microbubble contrast agents and concludes that characterisation
      should always be conducted in equilibrated, gas-saturated water to ensure
      accurate and repeatable measurements are made.

PMID- 22475698
TI  - Acute kidney injury and the critically ill patient.
AB  - Acute kidney injury (AKI) is a serious complication for the critically ill
      patient. The term has been increasingly adopted over recent years as efforts have
      been made to capture and better define mild to severe renal dysfunction.
      Persistent AKI can lead to the subsequent development of renal failure recognized
      as an important determinant of morbidity and mortality in the critically ill
      patient. This article explores the clinical implications of AKI for the
      critically ill patient and how this can have a profound influence on the
      principal presenting disease and expected outcome.

PMID- 22475700
TI  - Trends in caring for adult respiratory distress syndrome patients.
AB  - Acute respiratory distress syndrome is considered the most severe form of acute
      lung injury resulting in high morbidity and mortality. This syndrome is
      characterized by noncardiogenic pulmonary edema, diffuse pulmonary infiltrates,
      and hypoxemia refractory to oxygen delivery. Critical care nurses should be aware
      of newer treatment modalities available for patients with acute respiratory
      distress syndrome.

PMID- 22475701
TI  - Music therapy:  decreasing anxiety in the ventilated patient: a review of the
      literature.
AB  - Increased anxiety levels are a common problem for mechanically ventilated
      patients. Heightened anxiety and lack of effective treatment options result in
      negative patient outcomes. Music therapy has been documented as an effective
      nursing intervention to manage anxiety in ventilator-dependent patients. Seven
      studies examining the effectiveness of music therapy in ventilator-dependent
      patients are reviewed in this literature review.

PMID- 22475703
TI  - A personal reflection: what you need to know before getting involved in a
      clinical trial.
AB  - This brief article explains what you should know before agreeing to become a
      subject or participant in a clinical trial. Many people are asked every year to
      become involved in a clinical trial or research study. Of course, in almost all
      studies, you will be asked to sign an informed consent form after the study has
      been described to you in a satisfactory manner. However, some people do not truly
      understand the study and do not know exactly what they just agreed to do. What
      you need to know before agreeing to participate in research study is presented in
      this article.

PMID- 22475704
TI  - Prognostic communication of critical care nurses and physicians at end of life.
AB  - Many critical care nurses express reluctance to communicate prognostic
      information to patients and family members, especially prior to physician
      communication of this information. Yet, the findings from this study indicate
      that critical care nurses play a crucial, complementary role to physicians in
      prognostic communication. Nurses' contributions result in a broader picture of
      prognosis to patients and family members and facilitate end-of-life discussions.

PMID- 22475705
TI  - An undergraduate critical-care seminar: an innovative design for learning in the
      classroom.
AB  - There is a need for more innovative learning designs in nursing education. For
      optimal learning to occur, students need to take a more active part in their
      education. This article describes one institution's effort to design a critical
      care seminar class in a baccalaureate program. Students presented content in
      small groups on a predetermined topic.

PMID- 22475707
TI  - Nurse-driven titration of continuous insulin infusion in post-cardiac surgery
      patients.
AB  - This article describes the unique practice of nurse-driven titration of
      continuous insulin infusion in post-cardiac surgery patients in the intensive
      care unit at a tertiary care teaching hospital. A prospective quality assurance
      study was conducted to support our innovative practice.

PMID- 22475708
TI  - Evaluation of an evidence-based practice implementation: prophylactic amiodarone
      following coronary artery revascularization.
AB  - Postoperative atrial fibrillation is the most frequent dysrhythmia following
      coronary artery bypass grafting and is associated with complications, additional
      therapy, and longer hospital stays. Prophylactic amiodarone protocols have been
      validated as safe and beneficial in the prevention of atrial fibrillation
      following cardiac surgery. This study evaluates the use of our current treatment
      protocol, given prophylactically, as feasible and effective in producing similar
      outcomes in postoperative atrial fibrillation reduction as well as identifies any
      perioperative risk factors associated with this arrhythmia.

PMID- 22475710
TI  - Interdisciplinary collaboration applied to clinical research: an example of
      remote monitoring in lung transplantation.
AB  - Collaboration across disciplines is vital in clinical practice. It is also needed
      to generate high-quality actionable research, yet few frameworks for
      interdisciplinary collaboration exit to promote effective communications among
      researchers with common goals, but varied backgrounds. A review of what has been
      learned about collaboration was undertaken to determine attributes of effective
      interdisciplinary collaboration and barriers to its realization in patients
      undergoing lung transplantation.

PMID- 22475714
TI  - Nursing clinical practice in intensive care unit (ICU) settings.

PMID- 22475717
TI  - A guest editorial: what our patients notice.

PMID- 22475718
TI  - Phase II trial on the effects of Silexan in patients with neurasthenia, post
      traumatic stress disorder or somatization disorder.
AB  - Silexan, a novel lavender oil preparation for oral use, has been authorized in
      Germany for the treatment of states of restlessness during anxious mood. An open
      label, exploratory trial was performed to assess the potential of the medicinal
      product in the treatment of restlessness caused by anxiety as related to several
      disorders. Outcome measures included the Symptom Checklist-90-Revised (SCL-90-R),
      von Zerssen's Depression Scale (D-S), the 36-item Short Form Health Survey
      Questionnaire (SF-36), and a sleep diary. 50 male and female patients with
      neurasthenia (ICD-10 F48.0), post-traumatic stress disorder (PSD; F43.1), or
      somatization disorder (F45.0, F45.1) were included to receive 1 * 80 mg/day
      Silexan over 6 weeks; 47 could be analyzed for efficacy as full analysis set. At
      baseline, patients suffered from restlessness (96%), depressed mood (98%), sleep
      disturbances (92%), or anxiety (72%). Of those, resp. 62%, resp. 57%, resp.51%,
      resp. 62% showed improvements during treatment (p < 0.001). For all patients,
      mean D-S score decreased by 32.7% and SCL-90-R Global Severity Index by 36.4% as
      compared to baseline, (p < 0.001), while the SF-36 Mental Health Score increased
      by 48.2% (p < 0.001). Waking-up frequency (p = 0.002), Waking-up duration (p <
      0.001) and morning tiredness (p = 0.005) were reduced, while efficiency of sleep
      (p = 0.018) and mood (p = 0.03) improved. Patients suffering from neurasthenia or
      PSD showed comparable improvements with most outcomes. The results in this trial
      justify to further investigate Silexan in disorders with accompanying
      restlessness caused by sub-threshold anxiety. Adverse reactions, predominantly
      gastrointestinal complaints, were judged as mild or moderate.

PMID- 22475719
TI  - Biculturalism and Context: What Is Biculturalism, and When Is It Adaptive?:
      Commentary on Mistry and Wu.

PMID- 22475720
TI  - Water quality targets and maintenance of valued landscape character - experience
      in the Axe catchment, UK.
AB  - The Water Framework Directive (WFD) (Directive 2000/60/EC) requires new
      ecological standards for rivers, lakes and coastal waters by 2015. In the United
      Kingdom the English Catchment Sensitive Farming Initiative has identified 40
      catchments which are at risk of failing the European Commission WFD targets for
      good ecological status of water bodies because of a range of issues. The river
      Axe catchment situated in south-west England, with a mixture of diffuse and point
      sources of pollution, is one of these priority sites, as intensive dairy farming
      and cultivation of high risk crops (maize) cause problems with enhanced suspended
      sediment, nitrate and phosphorus levels in the river. Much of the Axe is under
      national and county landscape designations, making land use or management
      measures taken to achieve river status sensitive to these designations. For the
      purpose of this research the Soil and Water Assessment Tool (SWAT-2005) was used.
      The baseline scenario was based on field observation and interviews with the
      Environment Agency and farmers; it was run with and without point sources. Three
      different mitigation scenarios, designed to maintain the landscape of the
      catchment, were then tested. Field buffer strips (FBS), extensive land use
      management (EXT) and sheep land use management (SHP), were used to assess the
      effectiveness of the measures in reducing nutrient loads in the river Axe, UK.
      Management scenarios reduced the average annual loads at the main catchment
      outlet by 21.2% (FBS), 37.3% (EXT) and 45.0% (SHP), for total nitrogen and 47.7%
      (FBS), 60.6% (EXT) and 62.4% (SHP) for total phosphorus. The results of this
      study suggest that there may be a fundamental incompatibility between the
      delivery of WFD targets and the maintenance of viable agricultural systems
      necessary to maintain landscapes which are highly valued for their aesthetic,
      recreational and economic value.

PMID- 22475721
TI  - The influence of ultrasound guidance in the rate of success of acromioclavicular
      joint injection: an experimental study on human cadavers.
AB  - BACKGROUND: Injections of the acromioclavicular joint (ACJ) are performed
      routinely in patients with ACJ arthritis, both diagnostically and
      therapeutically. The aim of this prospective controlled study was to estimate the
      frequency of successful intra-articular ACJ injections with the aid of
      sonographic guidance versus non-guided ACJ injections. MATERIALS AND METHODS: A
      total of 80 cadaveric ACJs were injected with a solution containing methylene
      blue and subsequently dissected to distinguish intra- from peri-articular
      injections. In 40 cases the joint was punctured with sonographic guidance,
      whereas 40 joints were injected in the control group without the aid of
      ultrasound. RESULTS: The rate of successful intra-articular ACJ injection was 90%
      (36 of 40) in the guided group and 70% (28 of 40) in the non-guided group.
      Ultrasound was significantly more accurate for correct intra-articular needle
      placement (P = .025). DISCUSSION: The use of ultrasound significantly improves
      the accuracy of ACJ injection.

PMID- 22475722
TI  - Effect of packaging conditions on shelf-life of fresh foal meat.
AB  - The objective was to determine the shelf life of foal meat (Longissimus dorsi)
      stored in four different packages: (i) vacuum, (ii) overwrap and (iii) two
      modified atmospheres (MAP): high O(2) MAP (80% O(2)+20% CO(2)) and low O(2) MAP
      (30% O(2)+70% CO(2)) stored at 2  degrees C during 14 days. Shelf life evaluation
      was based on pH, colour, lipid and protein oxidation, microbial counts and
      sensory assessment of odour, colour and appearance. Based on aerobic bacterial
      counts, the shelf life of foal meat samples in overwrap and high O(2) MAP
      packages would be 10 days at most, almost 14 days in low O(2) MAP and more than
      14 days in vacuum packaging. Scores for sensorial evaluation were unacceptable
      after 10 days of storage in samples in overwrap and MAP packs, but they were
      still acceptable in vacuum ones. Moreover, for all packaging conditions except
      vacuum, which remained constant, a decrease in redness (a*) and an increase in
      carbonyl content and TBAR'S values was observed with storage time. High O(2)
      levels negatively affected foal meat quality, while anaerobic conditions extended
      shelf life to 14 days.

PMID- 22475723
TI  - Identification of differentially expressed proteins in curcumin-treated prostate
      cancer cell lines.
AB  - Due to high prevalence and slow progression of prostate cancer, primary
      prevention appears to be attractive strategy for its eradication. During the last
      decade, curcumin (diferuloylmethane), a natural compound from the root of
      turmeric (Curcuma longa), was described as a potent chemopreventive agent.
      Curcumin exhibits anti-inflammatory, anticarcinogenic, antiproliferative,
      antiangiogenic, and antioxidant properties in various cancer cell models. This
      study was designed to identify proteins involved in the anticancer activity of
      curcumin in androgen-dependent (22Rv1) and -independent (PC-3) human prostate
      cancer cell lines using two-dimensional difference in gel electrophoresis (2D
      DIGE). Out of 425 differentially expressed spots, we describe here the MALDI-TOF
      MS analysis of 192 spots of interest, selected by their expression profile. This
      approach allowed the identification of 60 differentially expressed proteins (32
      in 22Rv1 cells and 47 in PC-3 cells). Nineteen proteins are regulated in both
      cell lines. Further bioinformatic analysis shows that proteins modulated by
      curcumin are implicated in protein folding (such as heat-shock protein PPP2R1A;
      RNA splicing proteins RBM17, DDX39; cell death proteins HMGB1 and NPM1; proteins
      involved in androgen receptor signaling, NPM1 and FKBP4/FKBP52), and that this
      compound could have an impact on miR-141, miR-152, and miR-183 expression. Taken
      together, these data support the hypothesis that curcumin is an interesting
      chemopreventive agent as it modulates the expression of proteins that potentially
      contribute to prostate carcinogenesis.

PMID- 22475724
TI  - Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy
      in the WAVE(r) bioreactor.
AB  - BACKGROUND: To simplify clinical scale lymphocyte expansions, we investigated the
      use of the WAVE(r), a closed system bioreactor that utilizes active perfusion to
      generate high cell numbers in minimal volumes. METHODS: We have developed an
      optimized rapid expansion protocol for the WAVE bioreactor that produces
      clinically relevant numbers of cells for our adoptive cell transfer clinical
      protocols. RESULTS: TIL and genetically modified PBL were rapidly expanded to
      clinically relevant scales in both static bags and the WAVE bioreactor. Both
      bioreactors produced comparable numbers of cells; however the cultures generated
      in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less
      activated phenotype. CONCLUSIONS: The WAVE bioreactor simplifies the process of
      rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides
      an alternate approach to cell generation for ACT protocols.

PMID- 22475725
TI  - Chitosan oligosaccharide as potential therapy of inflammatory bowel disease:
      therapeutic efficacy and possible mechanisms of action.
AB  - Inflammatory bowel disease (IBD) results from intestinal epithelial barrier
      defect and dysregulated mucosal immune response. This study aimed to evaluate the
      therapeutic potential of chitosan oligosaccharide (COS), a biodegradation product
      of dietary fiber chitosan, in the treatment of IBD and to elucidate its possible
      mechanisms of action. Oral administration of COS protected against mortality and
      intestinal inflammation in a mouse model of acute colitis induced by 5% dextran
      sulfate sodium (DSS). The most effective dose range of COS was 10-20 mg/kg/day.
      In addition, nuclear factor kappa B (NF-kappaB) activation, and levels of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in colonic tissues
      were suppressed in mice receiving COS. Similar protective effect of COS against
      mortality and intestinal inflammation was observed in another mouse model of
      acute colitis induced by rectal instillation of 4% acetic acid. Importantly, COS
      administration after colitis induction was effective in ameliorating intestinal
      inflammation in both acute colitis models induced by 5% DSS and chronic colitis
      models induced by cycles of 2.5% DSS. In human colonic epithelial cells (T84
      cells), COS treatment prevented NF-kappaB activation, production of TNF-alpha and
      IL-6, and loss of epithelial barrier integrity under both lipopolysaccharide
      (LPS) and TNF-alpha-stimulated conditions. Furthermore, binding of LPS to T84
      cells, and TNF-alpha and oxidative stress-induced apoptosis of T84 cells were
      prevented by treatment with COS. These results suggest that COS may be effective
      in the treatment of IBD through inhibition of NF-kappaB signaling and apoptosis
      of intestinal epithelial cells.

PMID- 22475727
TI  - Treadmill gait speeds correlate with physical activity counts measured by cell
      phone accelerometers.
AB  - A number of important health-related outcomes are directly related to a person's
      ability to maintain normal gait speed. We hypothesize that cellular telephones
      may be repurposed to measure this important behavior in a noninvasive,
      continuous, precise, and inexpensive manner. The purpose of this study was to
      determine if physical activity (PA) counts collected by cell phone accelerometers
      could measure treadmill gait speeds. We also assessed how cell phone placement
      influenced treadmill gait speed measures. Participants included 55 young, middle
      aged, and older community-dwelling men and women. We placed cell phones as a
      pendant around the neck, and on the left and right wrist, hip, and ankle.
      Subjects then completed an individualized treadmill protocol, alternating 1 min
      rest periods with 5 min of walking at different speeds (0.3-11.3 km/h; 0.2-7
      mi/h). No persons were asked to walk at speeds faster than what they would
      achieve during day-to-day life. PA counts were calculated from all sensor
      locations. We built linear mixed statistical models of PA counts predicted by
      treadmill speeds ranging from 0.8 to 6.4 km/h (0.5-4 mi/h) while accounting for
      subject age, weight, and gender. We solved linear regression equations for
      treadmill gait speed, expressed as a function of PA counts, age, weight, and
      gender. At all locations, cell phone PA counts were strongly associated with
      treadmill gait speed. Cell phones worn at the hip yielded the best predictive
      model. We conclude that in both men and women, cell phone derived activity counts
      strongly correlate with treadmill gait speed over a wide range of subject ages
      and weights.

PMID- 22475726
TI  - Posturo-respiratory synchronization: effects of aging and stroke.
AB  - Spontaneous respiration influences the body's center-of-mass when standing. We
      contend that the healthy postural control system actively adapts to respiration,
      thereby minimizing its effect on postural sway. We therefore examined the
      interaction between respiration and postural sway, as measured by center-of
      pressure (COP) oscillations, and quantified the extent to which this interaction
      resulted in "posturo-respiratory synchronization." We hypothesized that
      synchronization would be stronger in elderly subjects and those with stroke, and
      when standing with eyes closed as compared to open, due to alterations in the
      physiologic mechanisms that normally regulate postural sway. Twenty-five subjects
      with chronic hemispheric infarction and 38 controls (50-80 years) stood on a
      force platform for 3 min with eyes-open and 3 min with eyes-closed. Respiratory
      flow and COP dynamics were simultaneously recorded. The dominant oscillatory mode
      of respiration and the corresponding oscillatory modes of anterioposterior and
      mediolateral COP dynamics were extracted using ensemble empirical mode
      decomposition. The strength of posturo-respiratory synchronization was quantified
      from the regularity of instantaneous phase shifts between extracted respiratory
      and COP oscillations. Significant posturo-respiratory synchronization was only
      present in the anterioposterior direction. The strength of synchronization
      increased with age (p<0.01). Closing the eyes increased synchronization strength
      in both groups (p=0.01), but more so in stroke patients (p=0.01). These
      observations suggest that a control system actively regulates the effects of
      respiration on sagittal-plane postural sway, particularly during eyes-open
      standing. As evidenced by increased posturo-respiratory synchronization with
      advanced age and central lesion, this novel metric may be used as a clinical
      marker of altered postural control.

PMID- 22475729
TI  - Mini-open retropleural transthoracic approach for the treatment of giant thoracic
      disc herniation.
AB  - STUDY DESIGN: We report on all patients treated for giant thoracic disc
      herniation in the past 10 years. OBJECTIVE: To specifically discuss our
      management of thoracic discs that occupy more than 40% of the canal and are thus
      defined as "giant" and to compare our surgical approach and technique with the
      previously published case series. SUMMARY OF BACKGROUND DATA: Giant herniated
      thoracic discs (HTDs) are recognized as a particular subset of thoracic disc
      pathology that require unique surgical consideration given their large volume,
      their often calcified nature, and the fact that the vast majority of patients
      have an already compromised spinal cord. It has been recommended that for
      successful resection of these discs an open thoracotomy, followed by a 2-level
      corpectomy and instrumentation, be performed. In the past decade, our institution
      has managed giant HTDs differently, using a mini-open retropleural thoracotomy,
      without the need for vertebrectomy or instrumentation in any case. METHODS:
      Seventeen cases of surgically treated giant HTDs were included in this study.
      Frankel grading system, 36-Item Short Form Health Survey, and Oswestry Disability
      Index assessed functional outcomes. RESULTS.: Seventeen patients underwent
      resection of a giant HTD between 2001 and 2010. The median postoperative length
      of stay was 5.5 days. All patients were myelopathic on presentation, Frankel
      scores ranged from B to D preoperatively. On long-term follow-up, 13 patients had
      improvement of their neurological status by 1 or 2 grades, 3 patients had no
      change in grade, and 1 patient died 38 days postoperation from pneumonia. No
      patient had neurological deterioration on long-term follow-up. CONCLUSION:
      Anterior exposure of the thoracic spine using a mini-open thoracotomy and
      retropleural approach coupled with a limited bony resection surrounding the giant
      disc, without corpectomy or instrumentation, represents an effective, safe, and
      appropriate surgical treatment for the resection of giant thoracic discs.

PMID- 22475730
TI  - Surgical management of symptomatic os odontoideum with posterior screw fixation
      performed using the magerl and harms techniques with intraoperative 3-dimensional
      fluoroscopy-based navigation.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the accuracy of
      screw fixation using intraoperative three-dimensional fluoroscopy-based
      navigation (ITFN) and to assess the clinical outcomes of this treatment regimen.
      SUMMARY OF BACKGROUND DATA: The surgical management of symptomatic os odontoideum
      poses considerable difficulties due to the highly variable anatomy of the upper
      cervical spine and surrounding neurovascular structures. Various methods have
      been described for the treatment of symptomatic os odontoideum, all of which have
      limitations. METHODS: Nineteen patients with symptomatic os odontoideum were
      investigated. Pain scores were assessed using the visual analogue scale.
      Myelopathy was assessed using the Nurick scale and Odom's criteria. Radiological
      imaging was carried out in all patients for diagnosis and to assess the
      atlantodens interval, space available for cord, and presence of intramedullary
      hyperintensity signals on T2-weighted images at the C1-C2 level. Posterior
      stabilization was performed for all patients by using ITFN. RESULTS: The mean
      Nurick score improved from 2.3 before surgery to 0.7 at the time of follow-up.
      The mean follow-up period was 34.7 months (range, 12-65 mo). According to Odom's
      criteria, outcomes were as follows: excellent, 47%; good, 37%; fair, 11%; and
      poor, 5%. All patients with preoperative neck pain had symptom relief or
      improvement, with all of these patients having more than 83.7% improvement in
      visual analogue scale scores. The mean preoperative space available for cord
      value of 9.3 mm improved to 17.7 mm. Solid fusion and reduction of atlantoaxial
      dislocation were achieved in every patient without screw failure. Sixty screws
      were placed in 19 patients. Two C2 polyaxial screws in 2 patients and 1
      transarticular screw in 1 patient slightly penetrated the transverse foramen with
      no vascular injury and clinical sequelae. CONCLUSION: ITFN is a safe, accurate,
      and effective tool for screw placement in patients with symptomatic os
      odontoideum.

PMID- 22475731
TI  - Methods to reduce outpatient non-attendance.
AB  - Non-attendance reduces clinic and provider productivity and efficiency,
      compromises access and increases cost of health care. This systematic review of
      the English language literature (November 1999-November 2009) compares telephone,
      mail, text/short message service, electronic mail and open-access scheduling to
      determine which is best at reducing outpatient non-attendance and providing net
      financial benefit. Telephone, mail and text/short message service interventions
      all improved attendance modestly but at varying costs. Text messaging was the
      most cost-effective of the 3, but its applicability may be limited. Few data are
      available regarding electronic mail reminders, whereas open-access scheduling is
      an area of active research.

PMID- 22475735
TI  - Outcome predictors of allogeneic hematopoietic stem cell transplant.
AB  - Acute kidney injury (AKI) is a significant complication after hematopoietic stem
      cell transplantation (HSCT) and frequently limits treatment success. Patients
      suffering complications with AKI often have high mortality. This investigation
      analyzed the outcomes of patients receiving allogeneic HSCT and identified the
      association between prognosis and RIFLE (risk of renal failure, injury to kidney,
      failure of kidney function, loss of kidney function and end-stage renal disease)
      classification. This study reviewed the medical records of 101 patients receiving
      allogeneic HSCT during an 8-year period at a specialized hematology ward in a
      university hospital in Taiwan. Demographic, clinical and laboratory variables
      were retrospectively gathered as predicators. Overall 6-month mortality was 36.6%
      (37/101). Mortality progressively and significantly increased (chi for trend, P <
      0.001) based on RIFLE classification severity. Multiple variable Cox regression
      analysis identified maximum RIFLE score on day 7 to 14 post-HSCT, occurrence of
      hepatic veno-occlusive disease and respiratory failure during admission as
      independent risk factors for 6-month mortality. Using the area under the receiver
      operating characteristic curve, the RIFLE classification on day 7 to 14 post-HSCT
      has the best discriminative power (area under the receiver operating
      characteristic curve: 0.696 +/- 0.057, P < 0.001) compared with day 0 to 7, 14 to
      30 and 30 to 60 post-HSCT. Cumulative survival rates at 6-month follow-up
      differed significantly (P < 0.05) among non-AKI, RIFLE-R versus RIFLE-I and RIFLE
      F. Hepatic veno-occlusive disease, respiratory failure and severity of maximum
      RIFLE score on day 7 to 14 post-HSCT were independent predictors for 6-month
      mortality. RIFLE classification on day 7 to 14 post-HSCT can improve the accuracy
      of 6-month mortality in patients who received allogeneic HSCT.

PMID- 22475734
TI  - Fever of unknown origin:  an evidence-based review.
AB  - Fever is a common problem for which patients seek medical advice. Fortunately, in
      most cases, fever is self-limiting or the etiology of fever is promptly
      established. Sustained, unexplained fever despite a comprehensive work up is
      recognized as fever of unknown origin (FUO), which frequently poses a clinical
      challenge. For a methodical approach, FUO is recently categorized into classic
      FUO, nosocomial FUO, neutropenic FUO and HIV-associated FUO based on the clinical
      setting and patient's underlying immune status. This review focuses on the key
      factors of classic FUO. The etiologic clues obtainable from the history, bedside
      physical examination findings and pertinent laboratory tests are discussed. Also,
      FUO in older patients and tuberculosis as a cause of FUO are briefly discussed.

PMID- 22475732
TI  - Beneficial effects of statins on endothelial progenitor cells.
AB  - In recent years, endothelial progenitor cells (EPCs) have been demonstrated to
      play an important role during tissue vascularization and endothelium homeostasis
      in adults. In addition, EPCs have been implicated in the pathophysiology of
      cardiovascular and cerebrovascular disease, such that a decreased number of EPCs
      may not only be a risk indicator but also a potential therapeutic target. Of the
      many agents that have been examined to increase EPCs and enhance their function,
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are one of
      the most intriguing. Accumulated evidence has demonstrated that statins promote
      EPC mobilization, proliferation, migration, adhesion, differentiation and reduce
      senescence and apoptosis independent of their serum lipid-lowering effect. This
      review summarizes the understanding of current mechanisms explaining the myriad
      of beneficial effects of statins on EPCs and discusses future challenges for
      studies involving statins and subpopulations of EPCs. However, the pharmacologic
      mechanisms of action of statins on EPCs remain at the cellular level, whereas the
      putative molecular mechanisms await further studies.

PMID- 22475745
TI  - Thermomechanical properties of graphene: valence force field model approach.
AB  - Using the valence force field model of Perebeinos and Tersoff (2009 Phys. Rev. B
      79 241409(R)), different energy modes of suspended graphene subjected to tensile
      or compressive strain are studied. By carrying out Monte Carlo simulations it is
      found that: (i) only for small strains (|epsilon| </~ 0.02) is the total energy
      symmetrical in the strain, while it behaves completely differently beyond this
      threshold; (ii) the important energy contributions in stretching experiments are
      stretching, angle bending, an out-of-plane term, and a term that provides
      repulsion against pi-pi misalignment; (iii) in compressing experiments the two
      latter terms increase rapidly, and beyond the buckling transition stretching and
      bending energies are found to be constant; (iv) from stretching-compressing
      simulations we calculated the Young's modulus at room temperature 350 +/- 3.15 N
      m(-1 ), which is in good agreement with experimental results (340 +/- 50 N m(-1
      )) and with ab initio results (322-353) N m(-1 ); (v) molar heat capacity is
      estimated to be 24.64 J mol(-1 ) K(-1 ) which is comparable with the Dulong-Petit
      value, i.e. 24.94 J mol(-1) K(-1), and is almost independent of the strain; (vi)
      nonlinear scaling properties are obtained from height-height correlations at
      finite temperature; (vii) the used valence force field model results in a
      temperature independent bending modulus for graphene, and (viii) the Gruneisen
      parameter is estimated to be 0.64.

PMID- 22475737
TI  - Long-term expansion of human foetal neural progenitors leads to reduced graft
      viability in the neonatal rat brain.
AB  - We previously reported that early passage human foetal neural progenitors (hFNPs)
      survive long-term in the rodent host brain whereas late passage cells disappear
      at later post-graft survival times. The extent to which this finding is related
      to changes in the expanded FNPs or in the adult host brain environment was not
      determined. Here we report the effect of expanding hFNPs for different periods of
      time in vitro on their ability to survive transplantation into the neonatal rat
      hippocampus, a generally more permissive environment than the adult rat brain.
      After 2 and 8 weeks in vitro, transplanted hFNPs formed large grafts, most of
      which survived well until at least 12 weeks. However, following continued
      expansion, hFNPs formed smaller grafts, and cells transplanted after 20 weeks
      expansion produced no surviving grafts, even at early survival times. To
      determine whether this could be due to a dilution of "true" neural stem cells
      through more differentiated progeny over time in culture, we derived homogeneous
      neural stem (NS) cells grown as a monolayer from the 8 week expanded hFNPs. These
      cells homogeneously expressed the neural stem cell markers sox-2, 3CB2 and nestin
      and were expanded for 5 months before transplantation into the neonatal rat
      brain. However, these cells exhibited a similar survival profile to the long-term
      expanded FNPs. These results indicate that, while the cellular phenotype of
      neural stem cells may appear to be stable in vitro using standard markers,
      expansion profoundly influences the ability of such cells to form viable grafts.

PMID- 22475738
TI  - [Diagnostic criteria for the Brugada syndrome: can they be improved?].
AB  - INTRODUCTION: Diagnosis of Brugada syndrome (BS) currently requires documentation
      of a characteristic repolarization pattern (type 1 Brugada ECG). Mutations in the
      SCN5A gene, which codes for sodium channel Na(v) 1.5, are found in 38% of
      familial cases of BS. Sodium current dysfunction negatively affects the cardiac
      fast response action potential, particularly in atrial and ventricular myocytes
      and in the fast-conducting Purkinje system. OBJECTIVES: To detect carriers of
      SCN5A mutations without using the characteristic repolarization pattern (type 1
      Brugada ECG). METHODS: Of a total of 141 members of three different families
      including 55 carriers of two nonsense SCN5A mutations causing BS, all those aged
      over 16 (113 individuals, 42 carriers) were studied. The PR interval (PR) and QT
      dispersion (QTd) between leads V1 and V3 were measured on conventional ECG. Using
      signal-averaged ECG the total duration of the filtered QRS complex (fQRS), the
      root-mean-square (RMS40) and the low-amplitude signal (LAS) were measured. The
      following procedures were developed to detect carriers/To detect carriers the
      following procedures were developed: (1) a screening test (ScreenTest) with PS
      (PR+fQRS) > or = 250 (250ms is 80% of the theoretical maximum in healthy
      individuals); and (2) a diagnostic test (DiagTest) for the simultaneous
      fulfillment of four conditions: PS > or = 250 and QTd > or = 10 and LAS > 26 and
      RMS40 < or = 29 (the latter two cut-offs are approximately 70% of the theoretical
      maximum in healthy carriers). RESULTS: Significant differences in PR, QTd, QRSf,
      RMS40 and LAS were found between carriers and non-carriers. The SCN5A gene was
      associated with all these variables, the strongest association being with PR.
      Both tests were applied to 63 family members (38 carriers). The ScreenTest was
      positive in 38 of 38 carriers, with eight false positives in 27 non-carriers
      (sensitivity [SE] = 100% and specificity [SP] = 66.67%). From ROC curve analysis
      a cut-off of PS = 252.5 shows SE = 100% and SP = 76% and a cut-off of PS = 260
      shows SE=94.7% and SP = 84%. The DiagTest was positive in 36 of 38 carriers, with
      three false positives: SE = 94.74% and SP = 88.89%. From ROC curve analysis a
      multivariate logistic model identifies a cut-off with SE = 92% and SP = 92%. In
      the same group the SE and SP of the characteristic spontaneous repolarization
      pattern (type 1 Brugada ECG) to detect carriers were 52.4% and 97.2%,
      respectively, and the difference between the SE of the DiagTest and of the
      typical repolarization pattern is statistically significant. CONCLUSIONS: The
      ScreenTest and DiagTest are more effective tools than the characteristic
      repolarization pattern to discriminate between carriers and non-carriers of these
      two nonsense SCN5A mutations. We suggest their use in first-degree relatives of
      Brugada patients when the results of genetic testing are not available, in a
      score of disease probability in individuals with idiopathic Brugada ECG, and in
      patients with arrhythmias or other Brugada-related symptoms presenting type 2 or
      type 3 Brugada ECG.

PMID- 22475744
TI  - The Varicella-zoster virus ORF54 gene product encodes the capsid portal protein,
      pORF54.
AB  - The Varicella-zoster virus (VZV) ORF54 gene was characterized using a guinea pig
      antiserum prepared to a GST-pORF54 fusion protein. A protein of the predicted
      size, 87kDa, was detected in VZV-infected MeWo cells but not in mock-infected
      cells. Sucrose density gradient fractionation of pORF54 expressed in a
      recombinant baculovirus system resulted in samples containing enriched amounts of
      pORF54. Electron microscopic analysis suggested that the ORF54 gene encodes a
      protein that assembles into ring-like portal structures similar to those observed
      for numerous bacteriophages and other herpesviruses.

PMID- 22475741
TI  - Swallowed fluticasone improves histologic but not symptomatic response of adults
      with eosinophilic esophagitis.
AB  - BACKGROUND & AIMS: We evaluated the effect of aerosolized fluticasone therapy on
      symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic
      esophagitis (EoE). METHODS: We performed a double-blind, randomized, placebo
      controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE
      (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that
      swallowed 880 MUg of aerosolized fluticasone twice daily (n = 21), or took a
      placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were
      symptomatic and histologic response. RESULTS: A complete histologic response
      (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who
      received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who
      received placebo (P < .001), based on intention-to-treat analysis; histologic
      responses were observed in 68% of subjects who received fluticasone (13 of 19)
      compared with none of those who received placebo (0 of 15) by per-protocol
      analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was
      reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8%
      who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of
      subjects who received fluticasone (12 of 21) compared with 33% who received
      placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced
      in 63% of patients who received fluticasone (12 of 19) and 47% of those who
      received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal
      candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but
      in none of the subjects in the placebo group (P = .05). CONCLUSIONS: Aerosolized,
      swallowed fluticasone leads to a histologic but not a symptomatic response in
      adults with EoE.

PMID- 22475742
TI  - High rates of viral suppression after long-term entecavir treatment of Asian
      patients with hepatitis B e antigen-positive chronic hepatitis B.
AB  - There are limited data on the effects of long-term entecavir therapy in Asian
      patients with chronic hepatitis B (CHB). We performed a post hoc analysis of 94
      Asian hepatitis B e antigen-positive (HBeAg+), nucleos(t)ide analogue-naive
      patients who received 5 years of therapy with entecavir (up to 2 years in study
      ETV-022 and the remainder in study ETV-901). Among patients completing week 240,
      95% (63 of 66) had levels of hepatitis B virus DNA <300 copies/mL, and 76% (50 of
      66) had normalized levels of alanine aminotransferase. In addition to patients
      who achieved a serologic response during ETV-022, a further 40% (26 of 65)
      achieved HBeAg loss, and 18% (12 of 65) underwent HBeAg seroconversion through
      year 5 of entecavir therapy. No resistance to entecavir was detected, and the
      safety profile was consistent with previous reports. The long-term efficacy and
      safety of entecavir are therefore comparable between Asians and the overall
      population of HBeAg+ patients with CHB.

PMID- 22475746
TI  - The development of simple and sensitive small-molecule fluorescent probes for the
      detection of serum proteins after native polyacrylamide gel electrophoresis.
AB  - In this paper, a simple and sensitive small-molecule fluorescent probe, 2,5
      dihydroxy-4'-dimethylaminochalcone (DHDMAC), was designed and synthesized for the
      detection of human serum proteins via hydrophobic interactions after
      polyacrylamide gel electrophoresis (PAGE). This probe produced lower fluorescence
      emission in the absence of proteins, and the emission intensity was significantly
      increased after the interaction with serum proteins. To demonstrate the imaging
      performance of this probe as a fluorescent dye, a series of experiments was
      conducted that included sensitivity comparison and 2D-PAGE. The results indicated
      that the sensitivity of DHDMAC staining is comparable to that of the most widely
      used fluorescent dye, SYPRO Ruby, and more protein spots (including thyroxine
      binding globulin, angiotensinogen, afamin, zinc-alpha-2-glycoprotein and alpha-1
      antichymotrypsin) were detected after 2D-PAGE. Therefore, DHDMAC is a good
      protein reporter due to its fast staining procedure, low detection limits and
      high resolution.

PMID- 22475736
TI  - Necrotizing fasciitis of the thigh secondary to retroperitoneal abscess.

PMID- 22475748
TI  - GO for integration of expression data.
AB  - The low reproducibility of differential expression of individual genes in
      microarray experiments has led to the suggestion that experiments be analyzed in
      terms of gene characteristics, such as GO categories or pathways, in order to
      enhance the robustness of the results. An implicit assumption of this approach is
      that the different experiments in effect randomly sample the genes participating
      in an active process. We argue that by the same rationale it is possible to
      perform this higher-level analysis on the aggregation of genes that are
      differentially-expressed in different expression-based studies, even if the
      experiments used different platforms. The aggregation increases the reliability
      of the results, it has the potential for uncovering signals that are liable to
      escape detection in the individual experiments, and it enables a more thorough
      mining of the ever more plentiful microarray data. We present here a proof-of
      concept study of these ideas, using ten studies describing the changes in
      expression profiles of human host genes in response to infection by Retroviridae
      or Herpesviridae viral families. We supply a tool (accessible at
      www.cs.bgu.ac.il/~waytogo) which enables the user to learn about genes and
      processes of interest in this study.

PMID- 22475743
TI  - ATM kinase is activated by sindbis viral vector infection.
AB  - Sindbis virus is a prototypic member of the Alphavirus genus, Togaviridae family.
      Sindbis replication results in cellular cytotoxicity, a feature that has been
      exploited by our laboratory for treatment of in vivo tumors. Understanding the
      interactions between Sindbis vectors and the host cell can lead to better virus
      production and increased efficacy of gene therapy vectors. Here we present
      studies investigating a possible cellular response to genotoxic effects of
      Sindbis vector infection. The Ataxia Telangiectasia Mutated (ATM) kinase, a
      sentinel against genomic and cellular stress, was activated by Sindbis vector
      infection at 3h post infection. ATM substrates, Mcm3 and the gammaH2AX histone,
      were subsequently phosphorylated, however, substrates involved with checkpoint
      arrest of DNA replication, p53, Chk1 and Chk2, were not differentially
      phosphorylated compared with uninfected cells. The ATM response suggests nuclear
      pertubation, resulting from cessation of host protein synthesis, as an early
      event in Sindbis vector infection.

PMID- 22475739
TI  - The ion channel transient receptor potential melastatin-2 does not play a role in
      inflammatory mouse models of chronic obstructive pulmonary diseases.
AB  - BACKGROUND: There is strong evidence that oxidative stress is associated with the
      pathogenesis of chronic obstructive pulmonary disease (COPD). The transient
      receptor potential melastatin-2 (TRPM2) is an oxidative stress sensing channel
      that is expressed in a number of inflammatory cells and therefore it has been
      suggested that inhibition of TRPM2 could lead to a beneficial effect in COPD
      patients. In this study, we have investigated the role of TRPM2 in a variety of
      mouse models of oxidative stress and COPD using TRPM2-deficent mice. METHODS:
      Mice were exposed to ozone (3 ppm for 4 h) or lipopolysaccharide (LPS, 0.3 mg/kg,
      intranasaly). In another model, mice were exposed to tobacco smoke (750 MUg/l
      total wet particulate matter) for 30 min twice a day on three consecutive days.
      For the exacerbation model, the smoke exposure on the morning of day 3 animals
      was replaced with intranasal administration of LPS (0.3 mg/kg). Animals were
      killed 3 and 24 h after the challenge (ozone and LPS model) or 18 h after the
      last tobacco smoke exposure. In vitro neutrophil chemotaxis and monocyte
      activation were also studied using cells isolated from wild type and TRPM2
      deficient animals. Statistical significance for the in vivo data (P < 0.05) was
      determined using analysis of variance with Kruskal-Wallis and Dunns multiple
      comparison test. RESULTS: In all models studied, no difference in the
      bronchoalveolar lavage inflammation could be evidenced when comparing wild type
      and TRPM2-deficient mice. In addition, no difference could be seen in the lung
      inflammation as assessed by the measurement of various cytokines/chemokines.
      Similarly in various in vitro cellular activation assays using isolated
      neutrophils and monocytes no significant differences could be observed when
      comparing wild type and TRPM2-deficient mice. DISCUSSION: We have shown, in all
      the models tested, no difference in the development of airway inflammation or
      cell activation between TRPM2-deficient mice and their wild type counterparts.
      These results would suggest that inhibiting TRPM2 activity in COPD would have no
      anti-inflammatory effect.

PMID- 22475751
TI  - Improving usability and accessibility of cheminformatics tools for chemists
      through cyberinfrastructure and education.
AB  - Some of the latest trends in cheminformatics, computation, and the world wide web
      are reviewed with predictions of how these are likely to impact the field of
      cheminformatics in the next five years. The vision and some of the work of the
      Chemical Informatics and Cyberinfrastructure Collaboratory at Indiana University
      are described, which we base around the core concepts of e-Science and
      cyberinfrastructure that have proven successful in other fields. Our chemical
      informatics cyberinfrastructure is realized by building a flexible, generic
      infrastructure for cheminformatics tools and databases, exporting "best of breed"
      methods as easily-accessible web APIs for cheminformaticians, scientists, and
      researchers in other disciplines, and hosting a unique chemical informatics
      education program aimed at scientists and cheminformatics practitioners in
      academia and industry.

PMID- 22475749
TI  - Gene expression data analysis using multiobjective clustering improved with SVM
      based ensemble.
AB  - Microarray technology facilitates the monitoring of the expression levels of
      thousands of genes over different experimental conditions simultaneously.
      Clustering is a popular data mining tool which can be applied to microarray gene
      expression data to identify co-expressed genes. Most of the traditional
      clustering methods optimize a single clustering goodness criterion and thus may
      not be capable of performing well on all kinds of datasets. Motivated by this, in
      this article, a multiobjective clustering technique that optimizes cluster
      compactness and separation simultaneously, has been improved through a novel
      support vector machine classification based cluster ensemble method. The
      superiority of MOCSVMEN (MultiObjective Clustering with Support Vector Machine
      based ENsemble) has been established by comparing its performance with that of
      several well known existing microarray data clustering algorithms. Two real-life
      benchmark gene expression datasets have been used for testing the comparative
      performances of different algorithms. A recently developed metric, called
      Biological Homogeneity Index (BHI), which computes the clustering goodness with
      respect to functional annotation, has been used for the comparison purpose.

PMID- 22475750
TI  - Fragment-based molecular design of new competitive dengue Den2 Ns2b/Ns3
      inhibitors from the components of fingerroot (Boesenbergia rotunda).

PMID- 22475754
TI  - Validation of claims data algorithms to identify nonmelanoma skin cancer.
AB  - Health maintenance organization (HMO) administrative databases have been used as
      sampling frames for ascertaining nonmelanoma skin cancer (NMSC). However, because
      of the lack of tumor registry information on these cancers, these ascertainment
      methods have not been previously validated. NMSC cases arising from patients
      served by a staff model medical group and diagnosed between 1 January 2007 and 31
      December 2008 were identified from claims data using three ascertainment
      strategies. These claims data cases were then compared with NMSC identified using
      natural language processing (NLP) of electronic pathology reports (EPRs), and
      sensitivity, specificity, positive and negative predictive values were
      calculated. Comparison of claims data-ascertained cases with the NLP demonstrated
      sensitivities ranging from 48 to 65% and specificities from 85 to 98%, with ICD-9
      CM ascertainment demonstrating the highest case sensitivity, although the lowest
      specificity. HMO health plan claims data had a higher specificity than all-payer
      claims data. A comparison of EPR and clinic log registry cases showed a
      sensitivity of 98% and a specificity of 99%. Validation of administrative data to
      ascertain NMSC demonstrates respectable sensitivity and specificity, although NLP
      ascertainment was superior. There is a substantial difference in cases identified
      by NLP compared with claims data, suggesting that formal surveillance efforts
      should be considered.

PMID- 22475757
TI  - Protein kinase C isoforms have differential roles in the regulation of human
      sebocyte biology.
AB  - Protein kinase C (PKC) isoforms have crucial roles in cutaneous signaling.
      Interestingly, we lack information about their involvement in human sebaceous
      gland biology. Therefore, in this current study, we investigated the functions of
      the PKC system in human immortalized SZ95 sebocytes. Using molecular biological
      approaches, imaging, and functional assays, we report that SZ95 sebocytes express
      the conventional cPKCalpha; the novel nPKCdelta, E, and eta; and the atypical
      aPKCzeta. Activation of the PKC system by phorbol 12-myristate 13-acetate (PMA)
      stimulated lipid synthesis (a hallmark of differentiation) and resulted in
      translocation and then downregulation of cPKCalpha and nPKCdelta. In good accord
      with these findings, the effect of PMA was effectively abrogated by inhibitors
      and short interfering RNA-mediated "silencing" of cPKCalpha and nPKCdelta. Of
      further importance, molecular or pharmacological inhibition of nPKCdelta also
      prevented the lipogenic and apoptosis-promoting action of arachidonic acid.
      Finally, we also found that "knockdown" of the endogenous aPKCzeta activity
      markedly increased basal lipid synthesis and apoptosis, suggesting its
      constitutive activity in suppressing these processes. Collectively, our findings
      strongly argue for the fact that certain PKCs have pivotal, isoform-specific,
      differential, and antagonistic roles in the regulation of human sebaceous gland
      derived sebocyte biology.

PMID- 22475752
TI  - ChemModLab: a web-based cheminformatics modeling laboratory.
AB  - ChemModLab, written by the ECCR @ NCSU consortium under NIH support, is a toolbox
      for fitting and assessing quantitative structure-activity relationships (QSARs).
      Its elements are: a cheminformatic front end used to supply molecular descriptors
      for use in modeling; a set of methods for fitting models; and methods for
      validating the resulting model. Compounds may be input as structures from which
      standard descriptors will be calculated using the freely available cheminformatic
      front end PowerMV; PowerMV also supports compound visualization. In addition, the
      user can directly input their own choices of descriptors, so the capability for
      comparing descriptors is effectively unlimited. The statistical methodologies
      comprise a comprehensive collection of approaches whose validity and utility have
      been accepted by experts in the fields. As far as possible, these tools are
      implemented in open-source software linked into the flexible R platform, giving
      the user the capability of applying many different QSAR modeling methods in a
      seamless way. As promising new QSAR methodologies emerge from the statistical and
      data-mining communities, they will be incorporated in the laboratory. The web
      site also incorporates links to public-domain data sets that can be used as test
      cases for proposed new modeling methods. The capabilities of ChemModLab are
      illustrated using a variety of biological responses, with different modeling
      methodologies being applied to each. These show clear differences in quality of
      the fitted QSAR model, and in computational requirements. The laboratory is web
      based, and use is free. Researchers with new assay data, a new descriptor set, or
      a new modeling method may readily build QSAR models and benchmark their results
      against other findings. Users may also examine the diversity of the molecules
      identified by a QSAR model. Moreover, users have the choice of placing their data
      sets in a public area to facilitate communication with other researchers; or can
      keep them hidden to preserve confidentiality.

PMID- 22475756
TI  - Pituitary tumor-transforming gene 1 enhances proliferation and suppresses early
      differentiation of keratinocytes.
AB  - The epidermis is a self-renewing tissue, the homeostasis of which is dependent
      upon the tight balance between proliferation and differentiation based on
      appropriate regulation of the cell cycle. The cell cycle regulation is dependent
      on the interactions among a number of cell cycle regulatory molecules, including
      the pituitary tumor-transforming gene 1 (PTTG1), also known as securin, a
      regulator of sister chromatid separation and transition from metaphase to
      anaphase. This study was conducted to clarify the less-known functions of PTTG1
      in the epidermis by the use of keratinocytes cultured under two-dimensional (2D)
      or three-dimensional (3D) conditions. Forced overexpression of PTTG1 caused
      upregulation of cyclin B1, cyclin-dependent kinase 1 (CDK1), and c-Myc, resulting
      in enhanced proliferation and suppression of early differentiation without
      apparent alterations in terminal differentiation, and the exogenous PTTG1 was
      downregulated in association with cell cycle exit. In contrast, depletion of
      PTTG1 caused their downregulation and constrained proliferation with retention of
      differentiation capacity. These findings suggested that PTTG1 could alter the
      proliferation status by modulating the expression levels of the other cell cycle
      regulatory proteins, and excess PTTG1 primarily affects early differentiation of
      keratinocytes under the stability regulation associated with cell cycle exit.

PMID- 22475755
TI  - The beta9 loop domain of PA-PLA1alpha has a crucial role in autosomal recessive
      woolly hair/hypotrichosis.

PMID- 22475747
TI  - Identification of common tumor signatures based on gene set enrichment analysis.
AB  - The identification of common tumor signatures can discover the shared molecular
      mechanisms underlying tumorgenesis whereby we can prevent and treat tumors by a
      system intervention. We identified tumor-associated signatures including
      pathways, transcription factors, microRNAs and gene ontology categories by
      analyzing gene sets for differential expression between normal vs. tumor
      phenotypes classes in various tumor gene expression datasets. We obtained the
      common tumor signatures based on their identified frequencies for different tumor
      types. Some shared signatures important for various tumor types were uncovered
      and discussed. We proposed that the interventions aiming at both the shared tumor
      signatures and the tissue-specific tumor signatures might be a potential approach
      to overcoming cancer.

PMID- 22475759
TI  - TRPV3 as a therapeutic target for itch.

PMID- 22475758
TI  - Aedes aegypti saliva enhances dengue virus infection of human keratinocytes by
      suppressing innate immune responses.

PMID- 22475753
TI  - Illuminator: increasing synergies between medicinal and computational chemists.
AB  - We present Illuminator, a user-friendly web front end to computational models
      such as docking and 3D shape similarity calculations. Illuminator was
      specifically created to allow non-experts to design and submit molecules to
      computational chemistry programs. As such it provides a simple user interface
      allowing users to submit jobs starting from a 2D structure. The models provided
      are pre-optimized by computational chemists for each specific target. We provide
      an example of how Illuminator was used to prioritize the design of molecular
      substituents in the Anadys HCV Polymerase (NS5B) project. With 7500 submitted
      jobs in 1.5 years, Illuminator has allowed project teams at Anadys to accelerate
      the optimization of novel leads. It has also improved communication between
      project members and increased demand for computational drug discovery tools.

PMID- 22475740
TI  - Best practices in endoscopic ultrasound-guided fine-needle aspiration.
AB  - Over the past 2 decades, endoscopic ultrasound-guided fine-needle aspiration has
      evolved to become an indispensable tool for tissue acquisition in patients with
      gastrointestinal tumors. The technique is useful for biopsy of mucosal and
      submucosal lesions in which prior endoscopic biopsies have been nondiagnostic; to
      sample peri-intestinal structures such as lymph nodes; and to sample masses in
      the pancreas, liver, adrenal glands, gallbladder, and bile duct. Also, with the
      advent of neoadjuvant therapies for diseases such as pancreatic cancer, most
      patients require a tissue diagnosis before initiating treatment. This review
      provides a perspective on technical issues that are key for best practices in
      endoscopic ultrasound-guided fine-needle aspiration.

PMID- 22475760
TI  - Melanoma genetics: recent findings take us beyond well-traveled pathways.
AB  - Genetic linkage and candidate gene studies have identified a number of genes
      involved in melanoma susceptibility, such as MC1R and CDKN2A, via the
      endophenotypes of pigmentation and nevus proliferation. A series of genome-wide
      association studies (GWASs) in 2008 and 2009 showed that a handful of additional
      genes (e.g., ASIP, TYR, and PLA2G6) influencing these endophenotypes also
      affected melanoma risk. The most recent wave of melanoma GWASs has uncovered
      genes functioning independently of the known melanoma-associated phenotypes,
      highlighting the role of processes such as DNA repair and cell cycle control. We
      take this opportunity to summarize these new and exciting findings and integrate
      them into the current framework of our understanding of melanoma genetics.

PMID- 22475762
TI  - Predictors of a difficult intubation in the bariatric patient: does preoperative
      body mass index matter?
AB  - BACKGROUND: The incidence of difficult intubations in morbidly obese patients has
      been reported to be 12-20%; however, no well-established predictors of a
      difficult intubation exist for this patient population. Our objective was to
      evaluate the factors associated with a difficult intubation in morbidly obese
      patients undergoing laparoscopic Roux-en-Y gastric bypass at an integrated
      multispecialty health system with a 325-bed community teaching hospital serving
      19 counties. METHODS: The anesthetic records of patients undergoing LRYGB from
      2001 to 2010 were reviewed. Difficult intubations were defined as direct
      laryngoscopy graded >=1 on a 0-2 difficulty scale and unplanned fiberoptic
      intubations. Statistical analysis included chi-square, univariate, and
      multivariate logistic regression. RESULTS: A total of 915 consecutive patients
      underwent LRYGB during the study period. Of these, 3 patients were excluded
      because of incomplete data. Of the 912 included patients, 25 (2.7%) underwent
      planned fiberoptic intubation, 830 (91%) had an uneventful intubation, and 57
      (6.3%) had a difficult intubation. Difficult intubations were more common in men
      than in women (11% versus 6%, P = .027). Difficult intubations were not
      associated with an increasing preoperative body mass index (P = .073), the
      presence of obstructive sleep apnea (P = .784), or the presence of
      gastroesophageal reflux disease (P = .335). Multivariate predictors of a
      difficult intubation were Mallampati class 4 (odds ratio [OR] 2.76, P = .035),
      abnormal thyromental distance (OR 4.39, P = .001), restricted jaw mobility (OR
      3.26, P = .018), and a history of a difficult intubation (OR 4.17, P = .002).
      CONCLUSIONS: An increased Mallampati class, abnormal thyromental distance,
      restricted jaw mobility, and a history of difficult intubations were independent
      predictors of a difficult intubation. An increasing body mass index did not
      predict for a difficult intubation.

PMID- 22475763
TI  - [Dosage of antipseudomonal antibiotics in patients with acute kidney injury
      subjected to continuous renal replacement therapies].
AB  - Critically ill patients are often affected by infections produced by Pseudomonas,
      which can be a cause of sepsis and renal failure. Early and adequate antibiotic
      treatment at correct dosage levels is crucial. Acute kidney injury is also
      frequent in critically ill patients. In those patients who require renal
      replacement therapy, continuous techniques are gaining relevance as filtering
      alternatives to intermittent hemodialysis. It must be taken into account that
      many antibiotics are largely cleared by continuous renal replacement therapies
      (CRRT). The aim of this review is to assess the clinical evidence on the
      pharmacokinetics and dosage recommendations of the main antibiotic groups used to
      treat Pseudomonas spp. infections in critically ill patients subjected to CRRT.

PMID- 22475761
TI  - Pharmacokinetic evaluation of pancreatic arterial infusion chemotherapy with
      lipid emulsion as a drug carrier in an animal model.
AB  - The purpose of this study was to investigate the potential pharmacokinetic
      advantage of pancreatic arterial infusion chemotherapy with lipid emulsion as a
      drug carrier for pancreatic cancer in a dog model. The 20% Intralipid, as a
      solvent, was used in the experimental animals with 2 ml/kg (group A) and 1 ml/kg
      (group B). Normal sodium as a solvent was used as a control with 2 ml/kg (group
      C) and 1 ml/kg (group D), respectively. Cisplatin (4 mg/kg) was infused into the
      proximal segment of the splenic artery. The concentrations of cisplatin were
      measured in plasma of the portal vein and in the liver and pancreas of groups A
      and C. The area under the concentration-time curve (AUC), the maximum plasma
      concentration (C(max)), and the elimination half-life (t(1/2)) in plasma were
      calculated and compared statistically. Compared with group C, the AUC and C(max)
      of group A were significantly lower (P<0.01 and P<0.01, respectively), the t 1/2
      was longer (P<0.05), and the tissue cisplatin concentration of the pancreas was
      higher (P<0.05). Compared with group D, the AUC and C(max) of group B were
      significantly lower (P<0.01 and P<0.01, respectively) and the t(1/2) was longer
      (P<0.01). Pancreatic arterial infusion chemotherapy with lipid emulsion as a drug
      carrier can increase the local concentration and prolong the retention time of a
      drug.

PMID- 22475764
TI  - New-onset diabetes after kidney transplantation: prevalence, risk factors, and
      management.
AB  - New-Onset Diabetes After Transplantation (NODAT) is an increasingly recognized
      severe metabolic complication of kidney transplantation causing lower graft
      function and survival and reduced long-term patient survival mainly due to
      cardiovascular events. The real incidence of NODAT after kidney transplantation
      is difficult to establish, because different classification systems and
      definitions have been employed over the years. Several risk factors, already
      present before or arising after transplantation, in particular the employed
      immunosuppressive regimens, have been related to the development of NODAT.
      However the responsible pathogenic mechanisms are still far to be perfectly
      known. Awareness of NODAT and of the NODAT-related factors is of paramount
      importance for the clinicians in order to individuate higher risk patients and
      arrange screening strategies. The risk of NODAT can be reduced by planning
      preventive measures and by tailoring immunosuppressive regimens according to the
      patient characteristics. Once NODAT has been diagnosed, the administration of
      specific anti-hyperglycemic therapy is mandatory to reach a tight glycemic
      control, which contributes to significantly reduce posttransplant mortality and
      morbidity.

PMID- 22475769
TI  - Drainage of a ventral epidural atlantoaxial abscess via the transoral approach.
AB  - We present a 28-year-old man with neck pain, fevers, elevated acute-phase
      reactant levels and progressive quadraparesis. He had a history of intravenous
      drug abuse. Contrast-enhanced cervical spine MRI revealed a heterogeneously
      enhancing mass in the anterior atlantoaxial region with spinal cord compression.
      The patient was taken emergently to the operating room for decompression.
      Although the transoral approach for access to the ventral atlantoaxial complex
      for resection of compressive inflammatory and neoplastic lesions is well
      described, reports of evacuation of infectious lesions via this route are
      limited. Thus, we report drainage of a ventral high cervical abscess via the
      transoral approach.

PMID- 22475768
TI  - Pisa syndrome in a patient with progressive supranuclear palsy.

PMID- 22475766
TI  - Plate-only open-door laminoplasty with fusion for treatment of multilevel
      degenerative cervical disease.
AB  - Adequate fixation of the opened laminar arch is the key indicator of a successful
      laminoplasty surgery; poor outcomes, including secondary narrowing of the spinal
      canal and a high risk of axial neck pain are possible when using a suturing
      method during conventional laminoplasty. Rigid fixation including spacers or bone
      struts yields satisfactory clinical outcomes. However, this approach is also
      associated with a longer surgical time and an increased risk of instrumentation
      dislodgement. Plate-only fixation with fusion was developed in our hospital to
      improve conventional laminoplasty; in addition, the supraspinous ligament is
      preserved in this procedure. We evaluated both the safety and efficacy of the
      procedure. Twenty-six patients with multilevel cervical degenerative disease were
      enrolled for selective open-door laminoplasty with miniplate fixation; autologous
      bone debris was placed on the hinge side to promote fusion, without bone struts
      on the open side. The Japanese Orthopedic Association (JOA) score, X-ray, three
      dimensional CT scan and MRI were used for the pre- and postoperative evaluations.
      The mean follow-up period was 22 months (range=12-34 months), and all patients
      achieved osseous fusion within six months of the operation. Patients who
      underwent open-door laminoplasty showed an improvement in the JOA score of 60.7%;
      a 23.0% incidence of axial neck pain and a 3.2 degrees  loss of range of motion
      (ROM) were also observed. No instrumentation failure or clinical deterioration
      was observed in our study. Thus, open-door laminoplasty with miniplate fixation
      is a safe, simple surgery for multilevel cervical disease that has significant
      clinical efficacy. This approach can maintain the cervical ROM, reduce the
      incidence of postoperative axial neck pain, decrease surgical time and cost, and
      avoid complications related to fusion.

PMID- 22475771
TI  - Four types of traditional Chinese medicine inducing epileptic seizures.
AB  - Traditional Chinese medicine has been used to treat disease in China for more
      than five thousand years. Over the last few decades it has been used increasingly
      in other countries as well. As its use has spread, interest in the adverse
      effects of traditional Chinese medicine, including epilepsy and epileptic
      seizures, has grown. To date, four types of traditional Chinese medicine have
      been found to induce epileptic seizures. In this review we will summarize the
      current knowledge about possible epileptogenic mechanisms of nux vomica, illicium
      henryi, betelnut and mulberry drawing on botanical, phytochemical, toxicological
      and animal studies.

PMID- 22475773
TI  - European Urology: an American perspective.

PMID- 22475770
TI  - The mechanisms mediating the effect of n-3 fatty acids on triglyceride (TG)
      biosynthesis in rats.

PMID- 22475767
TI  - Clinical analysis of cheiro-pedal syndrome.
AB  - Cheiro-pedal syndrome (CPS) is an incomplete pure sensory disorder confined
      strictly to simultaneous hand/finger and ipsilateral foot/toe symptoms. However,
      its clinical significance and pathogenesis are unclear. We present nine patients
      with typical CPS, and review another seven previously reported patients. Ischemic
      stroke is the leading cause of CPS in these 16 patients. In 13 patients, the
      lesions responsible were distributed widely in the brain from the corona radiata
      to the medulla oblongata whereas in three patients the lesions were found in the
      cervical spinal cord or peripheral nerves. All patients had a favorable outcome.
      The close proximity of the cheiral and pedal sensory fibers in the pons,
      thalamus, internal capsule and the caudal thalamocortical projection increases
      the vulnerability for CPS. Therefore, the underlying cause of CPS should be
      investigated rapidly despite it causing only minor symptoms. The pathogenesis of
      CPS may consist of several interacting factors including preconditioned neuronal
      damage and proximity of the acral sensory fibers.

PMID- 22475772
TI  - Thwarting high-risk prostate cancer: the right treatments for the right patients.

PMID- 22475765
TI  - Combined costimulatory and leukocyte functional antigen-1 blockade prevents
      transplant rejection mediated by heterologous immune memory alloresponses.
AB  - BACKGROUND: Recent evidence suggests that alloreactive memory T cells are
      generated by the process of heterologous immunity, whereby memory T cells arising
      in response to pathogen infection crossreact with donor antigens. Because of
      their diminished requirements for costimulation during recall, these pathogen
      elicited allocrossreactive memory T cells are of particular clinical importance,
      especially given the emergence of costimulatory blockade as a transplant
      immunosuppression strategy. METHODS: We used an established model of heterologous
      immunity involving sequential infection of a naive C57BL/6 recipient with
      lymphocytic choriomeningitis virus and vaccinia virus, followed by combined skin
      and bone marrow transplant from a BALB/c donor. RESULTS: We demonstrate that
      coupling the integrin antagonist anti-leukocyte functional antigen (LFA)-1 with
      costimulatory blockade could surmount the barrier posed by heterologous immunity
      in a fully allogeneic murine transplant system. The combined costimulatory and
      integrin blockade regimen suppressed proliferation of alloreactive memory T cells
      and attenuated their cytokine effector responses. This combined blockade regimen
      also promoted the retention of FoxP3+ Tregs in draining lymph nodes. Finally, we
      show that in an in vitro mixed lymphocyte reaction system using human T cells,
      the combination of belatacept and anti-LFA-1 was able to suppress cytokine
      production by alloreactive memory T cells that was resistant to belatacept alone.
      CONCLUSIONS: As an antagonist against human LFA-1 exists and has been used
      clinically to treat psoriasis, these findings have significant translational
      potential for future clinical transplant trials.

PMID- 22475774
TI  - Validation of quantitative real-time PCR for the in vitro assessment of
      antileishmanial drug activity.
AB  - In vitro assays play an important role in the discovery and development of new
      antileishmanial drugs. The classic macrophage-amastigote models using murine
      peritoneal macrophages or human-monocyte derived macrophages as host cells are
      useful for drug screening. A major limitation of these models is the dependence
      on microscopic counting, a time-consuming and subjective method of analysis. The
      present study describes a detailed protocol for applying quantitative real-time
      PCR (qPCR) as an accurate and sensitive tool to assess parasite load in an
      amastigote-macrophage model. This assay can be performed in a standardized medium
      to-high throughput procedure, replacing traditional readout of number of
      amastigote per macrophages by DNA load measurement.

PMID- 22475776
TI  - Dietary supplementation with chitin and chitosan on haematology and innate immune
      response in Epinephelus bruneus against Philasterides dicentrarchi.
AB  - The present study investigated the effect of 1.0% chitin and chitosan
      supplementation diets on haematology and immune response in Kelp grouper,
      Epinephelus bruneus against protozoan parasite, Philasterides dicentrarchi. The
      red blood cells (RBC), white blood cells (WBC), haemoglobin levels, lymphocytes,
      monocytes, and neutrophils significantly increased in kelp grouper fed with
      chitin or chitosan enriched diets against P. dicentrarchi. The mean corpuscular
      volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin
      concentration (MCHC), and thrombocytes did not significantly change against
      pathogen. The phagocytic activity, respiratory burst activity, complement
      activity, antiprotease activity, and alpha2-macroglobulin were significantly
      enhanced in fish fed with 1% chitin and chitosan diet on weeks 2 and 4. The
      lysozyme activity, total protein, and myeloperoxidase activity significantly
      increased in fish fed with chitin or chitosan supplementation diet from weeks 1
      to 4 against pathogen. The cumulative mortality was found low in fish fed with
      chitin and chitosan enriched diets than those of control against pathogen. The
      present study suggests that supplementation of 1.0% chitin or chitosan in diets
      positively enhances immune response and affords disease resistance in kelp
      grouper, E. bruneus against P. dicentrarchi infection.

PMID- 22475775
TI  - Activities of ectonucleotidases and adenosine deaminase in platelets of dogs
      experimentally infected with Rangelia vitalii.
AB  - Rangeliosis is a disease which affects dogs in Brazil, caused by a piroplasm
      known as Rangelia vitalii. This disease causes a lot of clinico-pathological
      features, including the coagulation disorders associated with bleeding. The cause
      of these changes has not yet been determined. Considering the association of
      purinergic system and hemostasis this study aimed to evaluate the activity of
      enzymes that hydrolyze ATP, ADP and AMP; and deamination of adenosine in
      platelets from dogs experimentally infected with R. vitalii. For this study, 12
      healthy young dogs (females) were used, separated in two groups. Group A (n=5)
      were uninfected controls, and group B were experimentally infected with R.
      vitalii (n=7). After being inoculated with R. vitalii-infected blood, animals
      were monitored by blood smear examinations, which showed intra-erythrocytic forms
      of the parasite after five days post-inoculation (PI). Blood samples were
      collected to quantitate and separate platelets (Day 0, 12 and 21 PI) and to
      measure the enzymatic activities (Day 12 and 21 PI). The activity of NTPDase, 5'
      nucleotidase and adenosine deaminase (ADA) was measured in platelets. A reduction
      (P<0.01) in the number of platelets was observed in R. vitalii-infected blood at
      Days 12 and 21 PI. At Day 12 PI, a reduction (P<0.01) in the hydrolysis of ATP,
      ADP and AMP, and deamination of adenosine was observed in dogs infected with R.
      vitalii. At Day 21 PI the ADA activity remained decreased, unlike the activity of
      NTPDase which increased (P<0.05). Based on these results we can conclude that
      ATP, ADP and AMP hydrolysis and adenosine deamination were altered in platelets
      of R. vitalii-infected dogs. Considering the importance of the purinergic system
      in hemostasis, it is believed that those changes contribute to the coagulation
      disorders and bleeding observed in R. vitalii-infected dogs and discussed in this
      manuscript.

PMID- 22475778
TI  - Airflow obstruction in never smokers in five Latin American cities: the PLATINO
      study.
AB  - BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is mostly
      related to tobacco smoking, a variable proportion of COPD occurs in never
      smokers. We investigated differences between COPD in never smokers compared with
      smokers and subjects without COPD. METHODS: PLATINO is a cross-sectional
      population-based study of five Latin American cities. COPD was defined as
      postbronchodilator FEV(1)/FVC <0.70 and FEV(1) <80% of predicted values. RESULTS:
      Among 5,315 subjects studied, 2278 were never smokers and 3036 were ever smokers.
      COPD was observed in 3.5% of never smokers and in 7.5% of ever smokers. Never
      smokers with COPD were most likely older and reported a medical diagnosis of
      asthma or previous tuberculosis. Underdiagnosis was as common in obstructed
      patients who never smoked as in ever smokers. CONCLUSIONS: Never smokers
      comprised 26% of all individuals with airflow obstruction. Obstruction was
      associated with female gender, older age and a diagnosis of asthma or
      tuberculosis.

PMID- 22475777
TI  - Association between PPAR-gamma and RXR-alpha gene polymorphism and metabolic
      syndrome risk: a case-control study of a Chinese Han population.
AB  - BACKGROUND AND AIMS: Polymorphisms in peroxisome proliferator activated receptor
      gamma (PPAR-gamma) and retinoid X receptor-alpha (RXR-alpha) gene may alter
      metabolic syndrome (MetS) risks by increasing or decreasing the human adiponectin
      promoter activity in cells. To test this statement, three potentially functional
      SNPs of PPAR-gamma and four SNPs of RXR-alpha with minor allele frequency (MAF)
      >=0.05 in the Chinese Han population were identified from NCBI dbSNPs database to
      evaluate their associations with MetS. METHODS: TaqMan assay was performed to
      test the genotypes in MetS patients (n = 901) and normal controls (n = 1009).
      Serum adiponectin concentration was measured by ELISA kit. RESULTS: The variant
      genotypes rs2920502CG and CG/CC, rs4240711GG and AG/GG, rs4842194CC and CT/CC,
      rs3132291CT, CC and CT/CC were associated with MetS. Furthermore, in the
      haplotype of PPAR-gamma gene, compared with the most common haplotype GC,
      haplotype CC was associated with an increased risk of MetS (crude p = 0.017). In
      the haplotype of RXR-alpha gene, haplotype GCGC was associated with a significant
      protective effect for MetS [adjusted p = 0.002, OR (95% CI) = 0.718 (0.585
      0.882)] compared with the most common haplotype GTAT. After taking smoking,
      alcohol consumption and physical activity as environmental adjustment factors
      into the analysis, the result showed A1 A2 A4 A5 A6 A7 B1 (rs3856806, rs2920502,
      rs180128, rs1045570, rs3132291, rs4240711, rs4842194) was the best model (cross
      validation consistency 10/10, p = 0.0107). CONCLUSIONS: The present study
      suggested that the variant genotypes in PPAR-gamma gene could increase the risk
      of MetS; however, genotypes in RXR-alpha gene could decrease the risk of MetS in
      a Chinese Han population.

PMID- 22475779
TI  - Interaction between endothelial nitric oxide synthase gene polymorphisms (
      786T>C, 894G>T and intron 4 a/b) and cardiovascular risk factors in acute
      coronary syndromes.
AB  - BACKGROUND AND AIMS: Endothelial rupture of coronary plaque can represent the
      pathomorphological substratum of acute coronary syndrome (ACS). Polymorphisms in
      the NOS3 gene (eNOS) -786T>C, 894G>T and intron 4 a/b VNTR can be associated with
      a higher susceptibility for ACS. The present study is focused on the
      investigation of the interaction of these polymorphisms and cardiovascular risk
      factors in 135 patients with ACS and 115 control subjects. METHODS: Case-control
      study where the allele and genotype frequencies of the polymorphisms -786T> C,
      894G> T and intron 4 VNTR of the gene encoding eNOS were determined by PCR-RFLP
      associated with cardiovascular risk factors. RESULTS: An association of the 894TT
      genotype and 894GT+GG (OR 1.4; 95% CI 1.0-1.8) in ACS has been observed. Subjects
      without dyslipidemia and intron 4 a/b genotype present a lower chance for ACS
      development, whereas subjects without diabetes and 894TT genotype show a higher
      risk for ACS (OR 1.7; 95% CI 1.2-2.3). In patients without dyslipidemia, the
      894GG genotype presented a tendency to behave as a protector factor against ACS.
      Also, the 894GG genotype has been a protective factor for ACS in females (OR 0.5;
      CI 95% 0.2-0.9). CONCLUSIONS: Our results suggest that eNOS polymorphisms may be
      an additional risk factor in development of ACS.

PMID- 22475781
TI  - Effectiveness of silver-enhanced in situ hybridization for evaluating HER2 gene
      status in invasive breast carcinoma: a comparative study.
AB  - BACKGROUND AND AIMS: HER2 gene amplification occurs in breast cancers and has
      implications for treatment and prognosis. Recently, a new direct evaluation
      technique, silver enhanced in situ hybridization (SISH) was developed for
      evaluating HER2 gene status. This study was performed to evaluate the SISH
      technique for clinical use by comparing it to that of fluorescence in situ
      hybridization (FISH) and immunohistochemistry (IHC). METHODS: We studied 543
      cases of excised breast specimens diagnosed as invasive ductal carcinoma by IHC,
      FISH, and SISH using a tissue microarray. IHC, FISH, and SISH results were
      interpreted according to the American Society of Clinical Oncology/College of
      American Pathologists guidelines. A total of seven English studies that reported
      the concordance rates of SISH and BDISH compared to FISH published before July
      2011 were retrieved. RESULTS: The consensus concordance rate between SISH and
      FISH was 96.69% (kappa value = 0.9175). The pooled sensitivity was 0.94 [95%
      confidence interval (CI) = 0.91-0.97], and the pooled specificity was 0.98 (95%
      CI = 0.96-099) in a meta-analysis of the retrieved studies and this study. Area
      under the receiver operating characteristics curve was 0.9906. CONCLUSIONS: SISH
      technique is an effective modality and is comparable with FISH for evaluating
      HER2 gene amplification in patients with breast carcinoma.

PMID- 22475780
TI  - Association between Val158Met functional polymorphism in the COMT gene and risk
      of preeclampsia in a Chinese population.
AB  - BACKGROUND AND AIMS: The catechol-O-methyltransferase (COMT) gene is a potential
      candidate in altering risk for preeclampsia due to the important enzymatic
      effects in the metabolism of steroid hormones. It contains a non-synonymous G-A
      base change at codon 158 in the membrane bound isoform, which leads to a valine
      to-methionine amino acid substitution. In the soluble isoform the polymorphism
      rs4680 is located in codon 108. The variant allele is the Met (A) allele and the
      Val (G) allele is the wild type allele. Despite its previously reported
      association with preeclampsia in genotypes in three selected ethnic groups,
      further studies in other populations are required. METHODS: We genotyped the
      Val158Met polymorphism in the COMT gene by polymerase chain reaction-restriction
      fragment length polymorphisms (PCR-RFLP) analysis in a Chinese population.
      RESULTS: In the case-control study that included 187 patients with preeclampsia
      (cases) and 189 normal subjects (controls), the AA genotype and variant Met
      allele frequencies of Val158Met in the COMT gene were significantly higher in
      patients with preeclampsia than those in the control group (both p <0.05). The
      odds ratio for the risk of preeclampsia was 2.395 [95% confidence interval (CI):
      1.061-5.408] in women homozygous for the variant COMT allele (chi(2) = 4.649, p =
      0.031). Furthermore, it showed that obese women homozygous for the variant COMT
      allele (Met/Met) had higher diastolic blood pressure levels during pregnancy than
      wild-type homozygotes (Val/Val) (p = 0.034). CONCLUSIONS: Our study provided
      evidence in favor of COMT being a candidate gene for conferring genetic
      susceptibility to preeclampsia in a South West Chinese population.

PMID- 22475782
TI  - Implementation of legal abortion in Nepal: a model for rapid scale-up of high
      quality care.
AB  - Unsafe abortion's significant contribution to maternal mortality and morbidity
      was a critical factor leading to liberalization of Nepal's restrictive abortion
      law in 2002. Careful, comprehensive planning among a range of multisectoral
      stakeholders, led by Nepal's Ministry of Health and Population, enabled the
      country subsequently to introduce and scale up safe abortion services in a
      remarkably short timeframe. This paper examines factors that contributed to
      rapid, successful implementation of legal abortion in this mountainous republic,
      including deliberate attention to the key areas of policy, health system
      capacity, equipment and supplies, and information dissemination. Important
      elements of this successful model of scaling up safe legal abortion include: the
      pre-existence of postabortion care services, through which health-care providers
      were already familiar with the main clinical technique for safe abortion;
      government leadership in coordinating complementary contributions from a wide
      range of public- and private-sector actors; reliance on public-health evidence in
      formulating policies governing abortion provision, which led to the embrace of
      medical abortion and authorization of midlevel providers as key strategies for
      decentralizing care; and integration of abortion care into existing Safe
      Motherhood and the broader health system. While challenges remain in ensuring
      that all Nepali women can readily exercise their legal right to early pregnancy
      termination, the national safe abortion program has already yielded strong
      positive results. Nepal's experience making high-quality abortion care widely
      accessible in a short period of time offers important lessons for other countries
      seeking to reduce maternal mortality and morbidity from unsafe abortion and to
      achieve Millennium Development Goals.

PMID- 22475783
TI  - Identification of an amphioxus intelectin homolog that preferably agglutinates
      gram-positive over gram-negative bacteria likely due to different binding
      capacity to LPS and PGN.
AB  - Intelectin is a recently described galactofuranose-binding lectin that plays a
      role in innate immunity in vertebrates. Little is known about intelectin in
      invertebrates, including amphioxus, the transitional form between vertebrates and
      invertebrates. We cloned an amphioxus intelectin homolog, AmphiITLN-like, coding
      302 amino acids with a conserved fibrinogen-related domain (FReD) in the N
      terminus and an Intelectin domain in the C-terminus. In situ hybridization in
      adult amphioxus showed that AmphiITLN-like transcripts were highly expressed in
      the digestive tract and the skin. Quantitative real-time PCR revealed that
      AmphiITLN-like is significantly up-regulated in response to Staphylococcus aureus
      challenge, but only modestly to Escherichia coli. In addition, recombinant
      AmphiITLN-like expressed in E. coli agglutinates Gram-negative and Gram-positive
      bacteria to different degrees in a calcium dependent manner. Recombinant
      AmphiITLN-like could bind lipopolysaccharide (LPS) and peptidoglycan (PGN), the
      major cell wall components of Gram-negative and Gram-positive bacteria,
      respectively, with a higher affinity to PGN. Our work identified and
      characterized for the first time an amphioxus intelectin homolog, and provided
      insight into the evolution and function of the intelectin family.

PMID- 22475784
TI  - The effects of microporosity on osteoinduction of calcium phosphate bone graft
      substitute biomaterials.
AB  - The effect of increasing strut porosity on the osteoinductive ability of silicate
      substituted calcium phosphate (SiCaP) biomaterials was investigated in an ectopic
      ovine model. Implants with strut porosities of 22.5%, 32.0% and 46.0% were
      inserted into the parapsinalis muscle. At 8, 12 and 24 weeks histological
      sections were prepared. Sections were examined using backscattered scanning
      electron microscopy and un-decalcified histology. Bone area, implant area and
      bone-implant contact were quantified. At 8 weeks there was no significant
      difference between the groups in terms of bone area and implant area. However at
      12 weeks, the amount of bone formation observed was significantly greater in
      SiCaP-46 (6.17 +/- 1.51%) when compared with SiCaP-22.5 (1.33 +/- 0.84%) p=0.035.
      Results also showed significantly increased amounts of bone-implant contact to
      the SiCaP-46 scaffold (3.30 +/- 1.17%) compared with SiCaP-22.5 (0.67 +/- 0.52%,
      p=0.043) at 8 weeks and 12 weeks; (SiCaP-46 (21.82 +/- 5.59%) vs SiCaP-22.5 (3.06
      +/- 1.89%), p=0.012). At 24 weeks, bone formation and graft resorption had
      significantly increased in all groups so that the level of bone formation in the
      SiCaP-46 group had increased 75-fold to 30.05 +/- 8.38%. Bone formation was
      observed in pores <10 MUm. Results suggest that bone graft substitute materials
      with greater strut porosity are more osteoinductive.

PMID- 22475786
TI  - In vivo kinematic analysis of cruciate-retaining total knee arthroplasty during
      weight-bearing and non-weight-bearing deep knee bending.
AB  - The purpose of the present study was to evaluate the in vivo kinematics of the
      posterior cruciate ligament-retaining total knee arthroplasty during weight
      bearing and non-weight-bearing deep knee bending and compare these 2 different
      conditions. We evaluated the in vivo kinematics of the knee using fluoroscopy and
      femorotibial translation relative to the tibia tray by 2-dimensional/3
      dimensional registration. In the weight-bearing state, the femoral component
      showed central pivot and bicondylar posterior rollback pattern. During non-weight
      bearing, the movement anteriorly occurred on both the medial and lateral side
      during early flexion, whereas bicondylar femoral component rollback occurred
      after that. During non-weight-bearing, both the medial and lateral condyle
      significantly moved anteriorly compared with the weight-bearing state during
      early flexion. However, bicondylar femoral rollback occurred under both these
      conditions.

PMID- 22475785
TI  - Rapid cell sheet detachment using spin-coated pNIPAAm films retained on surfaces
      by an aminopropyltriethoxysilane network.
AB  - The ability to harvest cell sheets grown on thermoresponsive polymers, such as
      poly(N-isopropylacrylamide) (pNIPAAm), has been widely studied for use in tissue
      engineering applications. pNIPAAm is of special interest because of the phase
      change that it undergoes in a physiologically relevant temperature range. Two
      primary approaches have been adopted to graft pNIPAAm chains covalently onto
      tissue culture polystyrene dishes: electron beam irradiation and plasma
      polymerization. These approaches often involve non-easily accessible (e.g. e
      beam) facilities and complicated procedures that have hindered most tissue
      culture laboratories in adopting this technology for their specific applications.
      In this study, we developed a simple and cost-effective approach to create
      thermoresponsive surfaces using commercially available pNIPAAm. Using a simple
      spin-coating technique, thermoresponsive thin films were deposited on glass
      slides or silicon wafers using pNIPAAm blended with a small amount of 3
      aminopropyltriethoxysilane (APTES), which enhances the retention of pNIPAAm on
      the surface. We found that the thermoresponsive films created using our method
      support cell attachment and proliferation without additional adhesive proteins as
      well as cell sheet detachment within minutes.

PMID- 22475787
TI  - Revision after total knee arthroplasty and unicompartmental knee arthroplasty in
      the Medicare population.
AB  - This study compares the relative risk of revision and associated risk factors
      after total or unicompartmental knee arthroplasty (TKA or UKA) in the Medicare
      population. A total of 61 767 TKA and 2848 UKA patients were identified. Reviewed
      data included type of treatment, gender, age, race, Charlson Index for
      comorbidity, length of stay, Medicare buy-in for socioeconomic status, region,
      and year. Unicompartmental knee arthroplasty patients were at increased risk for
      revision at 2 and 5 years. Those patients undergoing UKA were significantly more
      likely to require revision in the first 5 years as compared with those undergoing
      TKA. Risk factors contributing to TKA revision included younger male patients
      with higher comorbidities and lower socioeconomic status. About UKA, lower
      revision rates tend to favor those surgeons with higher volume.

PMID- 22475788
TI  - Next-generation education in crop genetics.
AB  - Today, plant breeders are being met with new opportunities to develop superior
      varieties. Fruitful genetic research into populations with novel diversity using
      genotyping by sequencing combined with genotype-to-phenotype bioinformatics has
      generated much knowledge that is directly relevant to crop improvement. These
      advances can assist the breeders in associating genetic makeup with traits of
      commercial value. The greatest challenge now is to find ways to attract the best
      young people to work in plant breeding for its innovation, open field experience
      and ability to support food security. We discuss the need, opportunities and
      conflicts associated with revamping plant breeding teaching programs to bridge
      the art and science of this profession with a rapidly expanding job market.

PMID- 22475789
TI  - [Kidney injury biomarkers].
AB  - Over the last few decades, prevalence of renal diseases has grown continuously in
      occidental societies due to life conditions (age, life style, chronic disease,
      etc.) or potential exposure to nephrotoxic agents (drugs and environmental
      chemicals). Today, the knowledge of the nephropatology mechanism is improving.
      Nevertheless, considering it is a complex and multifunctional structure, the
      clinical strategy of this issue (prognostic, diagnostic or therapy) keeps posing
      a major challenge for clinicians mostly because classical markers are not
      sensitive enough and require hours before reaching significant levels.
      Furthermore, most of these markers provide information on function and not on
      structural integrity of the tissue. Identification and development of new
      biomarkers share promise of improvement in the rapid diagnostic of kidney
      diseases and development of new cures in order to optimize the clinical strategy
      associated to the renal failure.

PMID- 22475790
TI  - Frequency dependence of the quasi-soft Raman-active modes in rotationally
      distorted R(3+)B(3+)O3 perovskites (R(3+)-rare earth, B(3+)=Al, Sc, Ti, V, Cr,
      Mn, Fe, Co, Ni, Ga).
AB  - The structural data and Raman spectra of distorted R(3+)B(3+)O(3) perovskites
      (R(3+)-rare earth, B(3+)=Al, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Ga) with BO(6)
      octahedral tilts were critically reviewed in order to obtain the frequency
      (omega) versus BO(6) tilt angle (alpha) dependence of the quasi-soft vibrational
      modes. It was found that the relation omega = kappaalpha is satisfied in a good
      approximation for each RBO(3) family with fixed B atom, despite the different
      spatial tilt orientations for compounds of the same series with either
      orthorhombic Pnma or rhombohedral R 3c structure. The dependence of the
      proportionality coefficient kappa on the averaged <B-O> octahedral distance can
      be described using different functions (power, linear and exponential ones). The
      established dependences can be used for analysis of Raman data and heuristic
      prediction of structural second-order transitions.

PMID- 22475791
TI  - Granular cell tumour in a patient with Crohn's disease treated with infliximab: 
      coincidence or causal relationship?
AB  - Granular cell tumour (or Abrikossoff's tumour) was first described by Abrikossoff
      in 1926. This is a rare benign neoplasm of unclear histogenesis that is generally
      believed to be of nerve sheath origin. Usually, it presents as a solitary lesion,
      located mainly in the subcutaneous tissue of the head, or the neck, or in the
      oral cavity, such as a tongue lesion, although it may develop anywhere in the
      body. Approximately 1-2% of granular cell tumours are malignant. Granular cell
      tumours are extremely rare in patients with inflammatory bowel disease. To the
      best of our knowledge, granular cell tumours have never been reported in
      association either with Crohn's disease or scheduled infliximab treatment.
      Herein, we report a case of a granular cell tumour that presented as a
      subcutaneous skin nodule of the right lumbar area without any associated local or
      systemic symptoms in a 41-year-old woman with Crohn's disease who was receiving
      scheduled treatment with infliximab (5 mg/kg every 8 weeks) for 7 years.

PMID- 22475792
TI  - Increasing materials' response to two-photon NIR light via self-immolative
      dendritic scaffolds.
AB  - Photoactivation using two photons of NIR allows non-invasive biological
      manipulation. We applied the principle of dendritic amplification to improve the
      materials' sensitivity to NIR light. Light induced uncaging or release of L
      glutamic acid was 2.8 fold higher when incorporating 4-bromo-7-hydroxycoumarin
      (Bhc) with self-immolative dendrimers compared with Bhc directly conjugated to L
      glutamic acid.

PMID- 22475793
TI  - Physical exercise exacerbates memory deficits induced by intracerebroventricular
      STZ but improves insulin regulation of H2O2 production in mice synaptosomes.
AB  - Insulin brain resistant state is associated with cognitive deficits and
      Alzheimer's disease by mechanisms that may involve mitochondrial damage and
      oxidative stress. Conversely, physical exercise improves cognitive function and
      brain insulin signaling. The intracerebroventricular (i.c.v.) administration of
      streptozotocin (STZ) in rodents is an established model of insulin-resistant
      brain state. This study evaluates the effects of physical exercise on memory
      performance of i.c.v., STZ-treated mice(1 and 3 mg/kg) and whether insulin (50
      and 100 ng/ml) modulates mitochondrial H2O2 generation in synaptosomes. S100B
      levels and SOD and CAT activities were assessed as markers of brain damage caused
      by STZ. Sedentary and exercise vehicle-treated mice demonstrated similar
      performance in object recognition memory task. In the water maze test, exercise
      vehicle-treated mice showed improvement performance in the acquisition and
      retrieval phases. The administration of STZ (1 mg/kg) before thirty days of
      voluntary physical exercise protocol impaired recognition and spatial memory only
      in exercised mice, whereas STZ (3 mg/kg) impaired the performance of sedentary
      and exercise groups. Moreover, STZ (3 mg/kg) increased hippocampal S100B levels
      in both groups and SOD/CAT ratio in the sedentary animals. Insulin decreased
      synaptosomal H2O2 production in exercised compared to sedentary mice; however,
      both STZ doses abolished this effect. Normal brain insulin signaling is
      mechanistically involved in the improvement of cognitive function induced by
      exercise through the regulation of mitochondrial H2O2 production. However, a
      prior blockade of brain insulin signaling with STZ abolished the benefits of
      exercise on memory performance and mitochondrial H2O2 regulation.

PMID- 22475794
TI  - APOE genotype and entorhinal cortex volume in non-demented community-dwelling
      adults in midlife and early old age.
AB  - The apolipoprotein E (APOE) epsilon4 allele is a risk factor for the
      neuropathological decline accompanying Alzheimer's disease (AD) while,
      conversely, the epsilon2 allele offers protection. One of the brain structures
      exhibiting the earliest changes associated with the disease is the entorhinal
      cortex. We therefore investigated the volumes of the entorhinal cortex and other
      structures in the medial temporal lobe including the parahippocampal gyrus,
      temporal pole, and inferior, middle, and superior temporal cortices, in relation
      to APOE genotype. Our main objectives were to determine if (a) volumes
      systematically varied according to allele in a stepwise fashion, epsilon2 >
      epsilon3 > epsilon4, and (b) associations varied according to age. We investigate
      this association in 627 non-demented community-dwelling adults in middle age (44
      to 48 years; n = 314) and older age (64 to 68 years; n = 313) who underwent
      structural MRI scans. We found no evidence of APOE-related variation in brain
      volumes in the age groups examined. We conclude that if a epsilon2 > epsilon3 >
      epsilon4 pattern in brain volumes does emerge in non-demented adults living in
      the community in old age, it is not until after the age of 68 years.

PMID- 22475795
TI  - Herpes simplex virus type I induces an incomplete autophagic response in human
      neuroblastoma cells.
AB  - Autophagy is a homeostatic process involved in the turnover or elimination of
      cytoplasmic components, damaged organelles, and protein aggregates via a
      lysosomal degradation mechanism. Autophagy also provides a mechanism of innate
      immunity, known as xenophagy, designed to protect cells from intracellular
      pathogens, but it may unfortunately be subverted to act as a pro-viral pathway
      facilitating the replication of certain viruses. Herpes simplex virus type I (HSV
      1) is a neurotropic virus that remains latent in host neurons; it is the most
      common cause of sporadic viral encephalitis. Moreover, HSV-1 has been related to
      the pathogenesis of Alzheimer's disease. HSV-1 can modulate the autophagic
      process through a mechanism mediated by the viral protein ICP34.5. Here we report
      that HSV-1 induces a strong increase in GFP-LC3 and endogenous LC3 lipidation,
      and triggers the accumulation of intracellular autophagic compartments (mainly
      autophagosomes) without enhancing autophagic long-lived protein degradation in
      the late stages of infection. Autophagy inhibition mediated by ATG5 gene
      silencing had no effect on viral growth. The present results suggest that HSV-1
      infection activates the host autophagic machinery and strongly controls the
      autophagic process, blocking the fusion of autophagosomes with lysosomes. These
      events might be important in the neurodegenerative process associated with HSV-1
      infection.

PMID- 22475796
TI  - Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive
      impairment.
AB  - Cerebrospinal fluid (CSF) measurements of amyloid-beta42 (Abeta42), total-tau (T
      tau), and phosphorylated tau (P-tau) may be used to predict future Alzheimer's
      disease (AD) dementia in patients with mild cognitive impairment (MCI). The
      precise temporal development of these biomarkers in relation to clinical
      progression is unclear. Earlier studies have been hampered by short follow-up. In
      an MCI cohort, we selected 15 patients who developed AD (MCI-AD) and 15 who
      remained cognitively stable during 4 years of follow-up. CSF was sampled at three
      serial occasions from each patient and analyzed for Abeta peptides, the soluble
      amyloid-beta protein precursor protein fragments sAbetaPPalpha and sAbetaPPbeta,
      T-tau, P-tau, and chromogranin B, which is a protein linked to regulated neuronal
      secretion. We also measured, for the first time in MCI patients, an extended
      panel of Abeta peptides by matrix-assisted-laser-desorption/ionization time-of
      flight mass spectrometry (MS). Most biomarkers were surprisingly stable over the
      four years with coefficients of variation below or close to 10%. However, MCI-AD
      patients decreased in CSF AbetaX-40 and chromogranin B concentrations, which may
      indicate a reduced number of functional neurons or synapses with disease
      progression. The MS Abeta peptide panel was more useful than any single Abeta
      peptide to identify MCI-AD patients already at baseline. Knowledge on these
      biomarkers and their trajectories may facilitate early diagnosis of AD and be
      useful in future clinical trials to track effects of disease modifying drugs.

PMID- 22475798
TI  - Copper in Alzheimer's disease: a meta-analysis of serum, plasma, and
      cerebrospinal fluid studies.
AB  - This contribution reviews and corrects data from our previous meta-analysis,
      which appeared in the Journal of Alzheimer's Disease in 2011 concerning the role
      of copper in Alzheimer's disease. We repeated the meta-analysis after excluding
      four of the five studies from our laboratory to avoid possible bias in the
      result. In addition, we included two studies on serum copper levels in
      Alzheimer's disease not previously considered. The results indicate higher levels
      of copper in Alzheimer's disease patients than in controls, confirming our
      previous conclusion.

PMID- 22475797
TI  - The French series of autosomal dominant early onset Alzheimer's disease cases:
      mutation spectrum and cerebrospinal fluid biomarkers.
AB  - We describe 56 novel autosomal dominant early-onset Alzheimer disease (ADEOAD)
      families with PSEN1, PSEN2, and AbetaPP mutations or duplications, raising the
      total of families with mutations on known genes to 111 (74 PSEN1, 8 PSEN2, 16
      AbetaPP, and 13 AbetaPP duplications) in the French series. In 33 additional
      families (23% of the series), the genetic determinism remained uncharacterized
      after this screening. Cerebrospinal fluid (CSF) biomarker levels were obtained
      for patients of 58 families (42 with known mutations and 16 without genetic
      characterization). CSF biomarkers profile was consistent with an AD diagnosis in
      90% of families carrying mutations on known genes. In families without mutation,
      CSF biomarkers were consistent with AD diagnosis in 14/16 cases. Overall, these
      results support further genetic heterogeneity in the determinism of ADEOAD and
      suggest that other major genes remain to be characterized.

PMID- 22475799
TI  - Prediction of S-glutathionylated proteins progression in Alzheimer's transgenic
      mouse model using principle component analysis.
AB  - To date, prediction of Alzheimer's disease (AD) is mainly based on clinical
      criteria because no well-established biochemical biomarkers for routine clinical
      diagnosis of AD currently exist. We developed an approach to aid in the early
      diagnosis of AD by using principal component analysis (PCA)-based spectral
      analysis of oxidized protein electrophoretic profiling. We found that the
      combination of capillary electrophoresis and PCA analysis of S-glutathionylation
      distribution characterization can be used in the sample classification and
      molecular weight (Mw) prediction. The comparison of leave-one-out AD versus non
      AD gives the sensitivity of 100% and 93.33% in brain tissues and blood samples,
      respectively, while the specificity of 100% in brain and 90.0% in blood samples.
      Our findings demonstrate that PCA of S-glutathionylation electrophoretic
      profiling detects AD pathology features, and that the molecular weight based
      electrophoretic profiling of blood and brain S-glutathionylated proteins are
      sensitive to change, even at the early stage of the disease. Our results offer a
      previously unexplored diagnostic approach by using electrophoretic
      characteristics of oxidized proteins to serve as a predictor of AD progression
      and early stage screening.

PMID- 22475800
TI  - Phospholipase C-eta activity may contribute to Alzheimer's disease-associated
      calciumopathy.
AB  - Alzheimer's disease (AD) is associated with altered neuronal Ca2+ homeostasis.
      Ca2+ is known to accumulate in AD-affected neurons leading to deficits in
      neurological activity that are characteristic of the disease. This has led to the
      coinage of the term "calciumopathy". However, the mechanisms of how and why Ca2+
      levels are increased in the AD-affected brain remain unknown. Identifying these
      mechanisms is crucial for our ability to treat and understand the disease
      processes that are occurring. Recent work has revealed the existence of a novel
      signaling pathway that may contribute toward this calciumopathy. Phospholipase C
      eta enzymes have recently been implicated in the modulation and amplification of
      Ca2+ signals and are known to be expressed in neuronal regions of the brain
      associated with cognition and memory. In this article their potential impact on
      neuronal Ca2+ signaling and AD pathogenesis is discussed.

PMID- 22475801
TI  - Dimebon ameliorates amyloid-beta induced impairments of mitochondrial form and
      function.
AB  - Due to their role in producing energy, as major sources of free radicals, and as
      critical regulators of apoptosis, mitochondria play a dominant role in the
      central nervous system (CNS). Mitochondrial dysfunction represents one major
      pathomechanism of Alzheimer's disease (AD), including impaired function of
      mitochondrial respiratory chain complexes and deficits of mitochondrial dynamics,
      such as impaired balance between fission and fusion mechanisms and reduced
      mitochondrial trafficking. Major consequences are enhanced depletion of
      mitochondria in axons and dendrites, synaptic dysfunction, and finally neuronal
      loss. Interfering with impaired mitochondrial dynamics has been proposed as novel
      strategy for antidementia drugs. Dimebon has been shown to improve cognition in
      animal models and seems to be beneficial in AD patients. Regardless of the final
      proof of Dimebon's clinical efficacy, it might specifically interfere with
      mechanisms relevant for the cognitive decline, especially by improving impaired
      mitochondrial function and/or dynamics in AD. Herein, we tested the effects of
      Dimebon on mitochondrial function and dynamics in a cellular model,
      overexpressing neurotoxic Abeta peptides, one of the hallmarks of AD. Dimebon
      exerted pronounced effects on mitochondrial morphology, respiratory chain complex
      activities, and enlarged mitochondrial mass. In summary, form and function of
      mitochondria are altered in the Abeta overexpressing cell model and precisely
      those changes are restored by nanomolar Dimebon treatment. Our findings support
      the idea that Dimebon improves mitochondrial function and that these "disease
      specific" effects might be relevant for interpretation and planning of future
      clinical trials.

PMID- 22475802
TI  - Mining biological information from 3D short time-series gene expression data: the
      OPTricluster algorithm.
AB  - BACKGROUND: Nowadays, it is possible to collect expression levels of a set of
      genes from a set of biological samples during a series of time points. Such data
      have three dimensions: gene-sample-time (GST). Thus they are called 3D microarray
      gene expression data. To take advantage of the 3D data collected, and to fully
      understand the biological knowledge hidden in the GST data, novel subspace
      clustering algorithms have to be developed to effectively address the biological
      problem in the corresponding space. RESULTS: We developed a subspace clustering
      algorithm called Order Preserving Triclustering (OPTricluster), for 3D short time
      series data mining. OPTricluster is able to identify 3D clusters with coherent
      evolution from a given 3D dataset using a combinatorial approach on the sample
      dimension, and the order preserving (OP) concept on the time dimension. The
      fusion of the two methodologies allows one to study similarities and differences
      between samples in terms of their temporal expression profile. OPTricluster has
      been successfully applied to four case studies: immune response in mice infected
      by malaria (Plasmodium chabaudi), systemic acquired resistance in Arabidopsis
      thaliana, similarities and differences between inner and outer cotyledon in
      Brassica napus during seed development, and to Brassica napus whole seed
      development. These studies showed that OPTricluster is robust to noise and is
      able to detect the similarities and differences between biological samples.
      CONCLUSIONS: Our analysis showed that OPTricluster generally outperforms other
      well known clustering algorithms such as the TRICLUSTER, gTRICLUSTER and K-means;
      it is robust to noise and can effectively mine the biological knowledge hidden in
      the 3D short time-series gene expression data.

PMID- 22475803
TI  - Positive end-expiratory pressure following coronary artery bypass grafting.
AB  - BACKGROUND: Cardiac surgery-related pulmonary complications include alterations
      in lung mechanics and anomalies in gas exchange. Higher levels of positive end
      expiratory pressure (PEEP) have been suggested to benefit cardiac surgical
      patients. We compared respiratory compliance, arterial oxygenation and time till
      tracheal extubation in 2 cohorts of patients weaned from mechanical ventilation
      with different levels of PEEP after elective and uncomplicated coronary artery
      bypass grafting (CABG). We hypothesized that higher PEEP levels improve pulmonary
      compliance and gas exchange in the first hours of weaning from mechanical
      ventilation, but not to shorten time till tracheal extubation. METHODS: Secondary
      retrospective analysis of 2 randomized controlled trials: in the first trial
      patients were weaned with PEEP levels of 10 cmH2O for the first 4 hours followed
      by PEEP levels of 5 cmH2O until tracheal extubation (high PEEP, HP); and the
      second trial patients were weaned with PEEP levels of 5 cmH2O during the entire
      weaning phase (low PEEP, LP). The primary endpoint was pulmonary compliance.
      Secondary endpoints included arterial oxygenation, duration of mechanical
      ventilation and postoperative pulmonary complications. RESULTS: The analysis
      included 121 patients; 60 HP patients and 61 LP patients. Baseline
      characteristics were similar. Compared to LP patients, HP patients had a better
      pulmonary compliance, 47.2+/-14.1 versus 42.7+/-10.2 ml/cmH2O (P<0.05), and
      higher levels of PaO2, 18.5+/-6.6 (138.75+/-49.5) versus 16.7+/-5.4 (125.25+/
      40.5) kPa (mmHg) (P<0.05). Patients in the HP group were less frequent in need of
      supplementary oxygen after ICU discharge. These differences remained present
      during the entire weaning phase, even after reduction of PEEP. However, HP
      patients had a longer time till tracheal extubation, 16.9+/-6.1 versus 10.5+/-5.0
      hours (P<0.001). HP patients had longer durations of postoperative infusion of
      propofol, 4.9 (2.6-7.4) versus 3.5 (1.8-5.8) hours (P<0.05). There were no
      differences in use of inotropes. Cumulative fluid balances were slightly higher
      in HP patients. CONCLUSION: Use of higher PEEP levels after elective
      uncomplicated CABG improves pulmonary compliance and oxygenation but seems to be
      associated with a delay in tracheal extubation.

PMID- 22475805
TI  - Outcome prediction in cardiac surgery: the first logistic scoring model for
      cardiac surgical intensive care patients.
AB  - BACKGROUND: In the process of risk stratification, a logistic calculation of
      mortality risk in percentage is easier to interpret. Unfortunately, there is no
      reliable logistic model available for postoperative intensive care patients. The
      aim of this study was to present the first logistic model for postoperative
      mortality risk stratification in cardiac surgical intensive care units. This
      logistic version is based on our previously presented and established additive
      model (CASUS) that proved a very high reliability. METHODS: In this prospective
      study, data from all adult patients admitted to our ICU after cardiac surgery
      over a period of three years (2007-2009) were collected. The Log-CASUS was
      developed by weighting the 10 variables of the additive CASUS and adding the
      number of postoperative day to the model. Risk of mortality is predicted with a
      logistic regression equation. Statistical performance of the two scores was
      assessed using calibration (observed/expected mortality ratio), discrimination
      (area under the receiver operating characteristic curve), and overall correct
      classification analyses. The outcome measure was ICU mortality. RESULTS: A total
      of 4054 adult cardiac surgical patients was admitted to the ICU after cardiac
      surgery during the study period. The ICU mortality rate was 5.8%. The
      discriminatory power was very high for both additive (0.865-0.966) and logistic
      (0.874-0.963) models. The logistic model calibrated well from the first until the
      13th postoperative day (0.997-1.002), but the additive model over- or
      underestimated mortality risk (0.626-1.193). CONCLUSION: The logistic model shows
      statistical superiority. Because of the precise weighing the individual risk
      factors, it offers a reliable risk prediction. It is easier to interpret and to
      facilitate the integration of mortality risk stratification into the daily
      management more than the additive one.

PMID- 22475804
TI  - Sedation practices in a cohort of critically ill patients receiving prolonged
      mechanical ventilation.
AB  - BACKGROUND: The aim of this paper was to describe type and amount of sedatives,
      opioid analgesics and anti- psychotics administered to critically ill patients
      receiving prolonged mechanical ventilation and identify patient-specific factors
      associated with their administration. METHODS: Retrospective cohort study of
      adult patients mechanically ventilated for >=14 days over a two-year period.
      RESULTS: The majority of patients (88%) received lorazepam for sedation (median
      14-day dose 168 mg, IQR 25-606). Morphine (median 14-day dose 125 mg, IQR 0-850)
      and fentanyl (median 14-day dose 2032 mcg, IQR 175-15346) were administered with
      relative equal frequency. Only 48% of the cohort received anti-psychotics during
      the first 14 days. Age was inversely associated with cumulative dose of lorazepam
      equivalents (ratio 0.97; 95% CI 0.95-0.99), propofol (ratio 0.93; 95% CI 0.89
      0.96), and morphine equivalents (ratio 0.97; 95% CI 0.96-0.98). Substance abuse
      was associated with cumulative dose of lorazepam (ratio 3.37; 95% CI 1.14-8.21)
      and morphine equivalents (ratio 3.09; 95% CI 1.48-6.44). Ethanol abuse was
      associated with >50% lower cumulative dose of morphine equivalents (ratio 0.47;
      95% CI 0.25-0.87). CONCLUSION: In critically ill patients receiving prolonged
      ventilation, history of substance abuse predicted a 3-fold increase in 14-day
      cumulative dose of sedatives and opioids used. Conversely, older age was
      associated with decreased use of sedatives and opioids and history of alcohol
      abuse was only associated with decreased opioid use. Overall, patients receiving
      prolonged mechanical ventilation appeared to consume high cumulative doses of
      sedatives and opioids, with less frequent use of antipsychotics. Accounting for
      patient characteristics may help identify individuals with varying sedative
      needs.

PMID- 22475806
TI  - Liver cirrhosis in the medical critical care patient.
AB  - Critically ill cirrhotic patients are characterized by unique and complicated
      clinical scenarios related to some characteristic and clear-cut
      pathophysiological features of their chronic end-stage liver disease that
      challenge Intensive Care Unit (ICU) physicians with several management problems.
      This class of patients may require admission to the ICU because of decompensation
      of their pre-existing liver disease or due to medical problems independent of
      cirrhosis as pneumonia, trauma or surgery. Either way, it is acknowledged that,
      when feasible, without definitive treatment by way of liver transplantation,
      cirrhosis is an independent predictor of poor outcome in critically ill patients.
      In fact, cerebral, cardiopulmonary and kidney dysfunctions as well as portal vein
      hypertension, ascites and gastrointestinal bleeding can make the course of these
      patients very complicated and may further affect their outcome. Despite some
      improvement that was recently reported, patients with decompensated cirrhosis
      pose to ICU physicians several and, sometimes, dramatic dilemmas in terms of
      therapeutic strategies and efficacy of the treatments also due to the lack of
      large specific studies on this particular class of patients. This review will
      focus on kidney, cardiopulmonary and cerebral complications of severe cirrhosis
      as well as those related to portal hypertension and their management.

PMID- 22475807
TI  - No additive effects of inhaled iloprost and prone positioning on pulmonary
      hypertension and oxygenation in acute respiratory distress syndrome.
AB  - BACKGROUND: In acute respiratory distress syndrome (ARDS), pulmonary hypertension
      is associated with a poor prognosis. Prone position is effective to improve
      oxygenation whereas inhaled iloprost can treat pulmonary hypertension. However,
      combination of these interventions has not been examined before. The hypothesis
      was that this combination had additive effects on oxygenation and pulmonary
      hemodynamics as compared with each intervention alone. METHODS: In a prospective,
      randomized cross-over study, ten pigs were anesthetized, intubated and ventilated
      with volume controlled ventilation. Carotid, jugular venous and pulmonary artery
      catheters were inserted. ARDS was induced with oleic acid (0.20 mL/kg).
      Measurements were repeated in randomized different sequences of prone or supine
      positions with or without iloprost inhalation (220 ng/kg/min) (four
      combinations). Systemic and pulmonary arterial pressures; arterial and mixed
      venous blood gases; and Qs/Qt and the resistances were recorded. RESULTS:
      Iloprost decreased pulmonary artery pressures (for MPAP: P=0.034) in both supine
      (37+/-10 vs. 31+/-8 mmHg; P<0.05) and prone positions (38+/-9 vs. 29+/-8 mmHg;
      P<0.05); but did not obtain a significant improvement in oxygenation in both
      positions. Prone position improved the oxygenation (p<0.0001) compared to supine
      position in both with (361+/-140 vs. 183+/-158 mmHg, P<0.05) or without iloprost
      application (331+/-112 vs. 167+/-117 mmHg, P<0.05); but did not achieve a
      significant decrease in MPAP. CONCLUSION: Although iloprost reduced pulmonary
      arterial pressures, and prone positioning improved oxygenation; there are no
      additive effects of the combination of both interventions on both parameters. To
      treat both pulmonary hypertension and hypoxemia, application of iloprost in prone
      position is suggested.

PMID- 22475808
TI  - Ultrasound guided cephalic vein cannulation (in the deltopectoral triangle) in
      severe hypoxemic non-invasive ventilated patient.

PMID- 22475809
TI  - n-3 and n-6 polyunsaturated fatty acids differentially regulate adipose
      angiotensinogen and other inflammatory adipokines in part via NF-kappaB-dependent
      mechanisms.
AB  - Excessive secretion of proinflammatory adipokines has been linked to metabolic
      disorders. We have previously documented anti-inflammatory effects of n-3
      polyunsaturated fatty acids (n-3 PUFAs) in adipose tissue; however, the
      mechanisms by which these fatty acids regulate adipokine secretion remain
      unclear. Here, we determined differential effects of eicosapentaenoic acid (EPA,
      n-3 PUFA) vs. arachidonic acid (AA, n-6 PUFA) on expression and secretion of
      angiotensinogen (Agt), interleukin 6 (IL-6) and monocyte chemotactic protein (MCP
      1) in 3T3-L1 adipocytes. While both PUFAs increased intracellular Agt protein and
      mRNA expression, Agt secretion into culture media was increased only by AA
      treatment, which in turn was prevented by co-treatment with EPA. At various
      AA/EPA ratios, increasing AA concentrations significantly increased secretion of
      the above three adipokines, whereas increasing EPA dose-dependently, while
      lowering AA, decreased their secretion. Moreover, IL-6 and MCP-1 were more
      significantly reduced by EPA treatment compared to Agt (IL-6>MCP>Agt). Next, we
      tested whether nuclear factor-kappaB (NF-kappaB), a major proinflammatory
      transcription factor, was involved in regulation of these adipokines by PUFAs.
      EPA significantly inhibited NF-kappaB activation compared to control or AA
      treatments. Moreover, EPA attenuated tumor necrosis factor-alpha-induced MCP-1
      and further reduced its secretion in the presence of an NF-kappaB inhibitor.
      Taken together, we reported here novel beneficial effects of EPA in adipocytes.
      We demonstrated direct anti-inflammatory effects of EPA, which are at least in
      part due to the inhibitory effects of this n-3 PUFA on the NF-kappaB pathway in
      adipocytes. In conclusion, these studies further support beneficial effects of n
      3 PUFAs in adipocyte inflammation and metabolic disorders.

PMID- 22475810
TI  - The role of PKC isoforms in the inhibition of NF-kappaB activation by vitamin K2
      in human hepatocellular carcinoma cells.
AB  - Vitamin K (VK) has diverse protective effects against osteoporosis,
      atherosclerosis and carcinogenesis. We recently reported that menatetrenone, a
      VK2 analogue, suppressed nuclear factor (NF)-kappaB activation in human hepatoma
      cells. Although NF-kappaB is regulated by isoforms of protein kinase C (PKC), the
      involvement of PKCs in VK2-mediated NF-kappaB inhibition remains unknown.
      Therefore, the effects of VK2 on the activation and the kinase activity of each
      PKC isoform were investigated. The human hepatoma Huh7 cells were treated with
      PKC isoform-specific inhibitors and/or siRNAs against each PKC isoform with or
      without 12-O-tetradecanoylphorbol-13-acetate (TPA). VK2 inhibited the TPA-induced
      NF-kappaB activation in Huh7 cells. NF-kappaB activity was inhibited by the pan
      PKC inhibitor Ro-31-8425, but not by the PKCalpha-specific inhibitor Go6976. The
      knockdown of individual PKC isoforms including PKCalpha, delta and E showed only
      marginal effects on the NF-kappaB activity. However, the knockdown of both
      PKCdelta and PKCE, together with treatment with a PKCalpha-specific inhibitor,
      depressed the NF-kappaB activity. VK2 suppressed the PKCalpha kinase activity and
      the phosphorylation of PKCE after TPA treatment, but neither the activation nor
      the enzyme activity of PKCdelta was affected. The knockdown of PKCE abolished the
      TPA-induced phosphorylation of PKD1, and the effects of PKD1 knockdown on NF
      kappaB activation were similar to those of PKCE knockdown. Collectively, all of
      the PKCs, including alpha, delta and E, and PKD1 are involved in the TPA-mediated
      activation of NF-kappaB. VK2 inhibited the NF-kappaB activation through the
      inhibition of PKCalpha and E kinase activities, as well as subsequent inhibition
      of PKD1 activation.

PMID- 22475811
TI  - Mammalian mismatch repair: error-free or error-prone?
AB  - A considerable surge of interest in the mismatch repair (MMR) system has been
      brought about by the discovery of a link between Lynch syndrome, an inherited
      predisposition to cancer of the colon and other organs, and malfunction of this
      key DNA metabolic pathway. This review focuses on recent advances in our
      understanding of the molecular mechanisms of canonical MMR, which improves
      replication fidelity by removing misincorporated nucleotides from the nascent DNA
      strand. We also discuss the involvement of MMR proteins in two other processes:
      trinucleotide repeat expansion and antibody maturation, in which MMR proteins are
      required for mutagenesis rather than for its prevention.

PMID- 22475812
TI  - [Development and validation of a questionnaire to measure hospitals' social
      reputation].
AB  - OBJECTIVE: To design and validate a questionnaire (MeFio) to measure the social
      reputation of a hospital from patients' and citizens' perspective. MATERIAL AND
      METHODS: We performed a literature review to define the concept of a hospital's
      social reputation. Four nominal groups were conducted to set up the a priori
      factors of the MeFio questionnaire. These groups consisted of 47 managers and
      health professionals and 32 potential customers. Reactive items were identified
      and a pilot test was conducted to examine comprehension. A random sample of 385
      subjects was selected. Ceiling and floor effects, internal consistency,
      reliability, and construct and criteria validity were analyzed. RESULTS: A total
      of 343 validated questionnaires (response rate 89%) were collected. The MeFio
      questionnaire has 21 items grouped into five factors. All items had an item-total
      correlation higher than 0.30. All factor loads were higher than 0.5; between
      66.2% and 80.4% of the variance was explained and Cronbach's alpha was 0.7- 0.88.
      The construct-composite-reliability scores were higher than 0.7. Standardized
      scores in the convergent discriminant validity test were higher than 0.6. The
      factors explained 50% of the variability in satisfaction with the health care
      received (F = 66.5; p <0.001). CONCLUSION: The MeFio questionnaire is a valid and
      reliable tool to measure the five dimensions that define the reputation of a
      hospital in Spain.

PMID- 22475813
TI  - [Are studies of geographical variation in medical practice useful in guiding
      decisions on disinvestment? Some pros and cons].
AB  - OBJECTIVE: Disinvestment has been defined as the explicit process of cutting
      funding, either totally or partially, from health technologies deemed of low
      value. Studies of geographic variation in medical practice have been suggested to
      be useful in guiding decisions on disinvestment, as they may identify unwarranted
      variations in procedure-rates at the population level. This study aimed to
      determine the utility of these studies. METHODS: We performed an ecologic study
      of variations in standardized rates in four "low-value" interventions:
      proctologic surgery, arthroplasty revision, incisional hernia repair and
      tonsillectomy. Variation across 199 healthcare areas within the Spanish national
      health system between 2002 and 2007 was studied by using the extremal quotient
      (EQ), the empirical Bayes statistic (EB) and the standardized utilization ratio
      (SUR). RESULTS: A total of 168,363 proctologic interventions, 41,066 arthroplasty
      revisions, 222,427 incisional hernia repairs, and 72,724 tonsillectomies were
      studied. The EQ ranged from a 3-fold variation in proctologic surgery to a 6.5
      fold variation in tonsillectomy. The EB figures varied from moderate to high
      systematic variation: 0.12 in hernia repair and proctology, 0.20 in arthroplasty
      revision, and 0.30 in tonsillectomy. Twenty-five percent of the healthcare areas
      showed SUR figures above 1.24 in proctologic interventions, 1.25 in arthroplasty
      revision, 1.32 in hernia repair and 1.35 in tonsillectomy. CONCLUSIONS: The
      interventions studied showed moderate to high systematic variation, supporting
      the usefulness of variation studies in guiding disinvestment policies.
      Nevertheless, caution should be exercised when evaluating interventions with an
      uncertain risk-benefit ratio.

PMID- 22475814
TI  - Comparison of impulsivity and working memory in cocaine addiction and
      pathological gambling: Implications for cocaine-induced neurotoxicity.
AB  - BACKGROUND: The aim of this study was to compare the cognitive performance of
      cocaine dependent individuals (CDI) with that of pathological gamblers (PG).
      Cocaine dependence and pathological gambling share neurobiological
      vulnerabilities related to addiction, but PG are relatively free of the toxic
      consequences, such that any additional deficits observed in CDI may be
      interpreted as pertaining to specific drug effects. METHODS: We used a case
      control observational design contrasting multiple measures of impulsivity (UPPS-P
      trait impulsivity, delay discounting) and executive measures of response
      inhibition (Stroop) and working memory performance (N-back) between groups of CDI
      (n=29), PG (n=23), and healthy controls (n=20). We conducted one-way ANOVAs,
      followed by planned pairwise tests and calculations of Cohen's d to estimate
      significant differences between the groups. RESULTS: CDI, as compared to PG, had
      elevated scores on UPPS-P Negative Urgency and poorer performance on working
      memory (2-back). PG had steeper delay-discounting rates. Both groups had elevated
      Positive Urgency and poorer Stroop inhibition compared to controls. Peak amount
      of cocaine use was negatively correlated with working memory and response
      inhibition performance. CONCLUSION: We found cocaine-related specific elevations
      in Negative Urgency and working memory deficits, putatively identified as cocaine
      neurotoxicity effects. Other aspects of impulsivity (Positive Urgency, Stroop
      inhibition) were increased across CDI and PG groups and may reflect vulnerability
      factors for addiction.

PMID- 22475815
TI  - Estimated magnitude of diversion and abuse of opioids relative to benzodiazepines
      in France.
AB  - INTRODUCTION: Prescription drug abuse is a major concern in several countries.
      France appears to be particularly prone to the abuse of opiate maintenance
      treatment (OMT) opioids and benzodiazepines (BZD), whereas the abuse of opioid
      analgesics (OA) is less commonly reported. To estimate the extent of psychoactive
      drug abuse, the French drug agency relies on different methods measuring various
      diversion indicators used as proxies for the detection of abuse/misuse: suspicion
      of abuse/dependence, illegal acquisition by patients seen in specialized care
      centers, prescription forgery and doctor shopping. The main objectives of the
      present study are to analyse the abuse and diversion of opioids (both OA and
      OMT), in comparison with those of BZDs, through the concurrent use of three
      different data sources. METHODS: Diversion and abuse of opioids were analysed
      using indicators of abuse and diversion derived from three data sources over the
      period 2006-2008. Then, opioids were compared to BZDs for the year 2008 using the
      same indicators. RESULTS: The analysis suggests that BZDs are more commonly
      dispensed than OAs and OMTs but that abuse and diversion are related mainly to
      OMT (particularly to buprenorphine), morphine and BZDs and less to OAs (except
      for morphine). CONCLUSION: This study presents an original approach, based on the
      use of multiple data sources, to evaluate and compare the estimated abuse and
      diversion of opioids and benzodiazepines. It provides health authorities with a
      global, comparative and summarized overall view of the importance of different
      patterns of diversion and abuse for different prescription drugs.

PMID- 22475817
TI  - Molecular phylogeny of African bush-shrikes and allies: tracing the biogeographic
      history of an explosive radiation of corvoid birds.
AB  - The Malaconotidea (e.g., butcherbirds, bush-shrikes, batises, vangas) represent
      an Old World assemblage of corvoid passerines that encompass many different
      foraging techniques (e.g., typical flycatchers, flycatcher-shrikes, canopy
      creepers, undergrowth skulkers). At present, relationships among the primary
      Malaconotidea clades are poorly resolved, a result that could either be
      attributed to a rapid accumulation of lineages over a short period of time (hard
      polytomy) or to an insufficient amount of data having been brought to bear on the
      problem (soft polytomy). Our objective was to resolve the phylogenetic
      relationships and biogeographic history of the Malaconotidea using DNA sequences
      gathered from 10 loci with different evolutionary properties. Given the range of
      substitution rates of molecular markers we sequenced (mitochondrial, sex-linked,
      autosomal), we also sought to explore the effect of altering the branch-length
      prior in Bayesian tree estimation analyses. We found that changing the branch
      length priors had no major effect on topology, but clearly improved mixing of the
      chains for some loci. Our phylogenetic analyses clarified the relationships of
      several genera (e.g., Pityriasis, Machaerirhynchus) and provide for the first
      time strong support for a sister-group relationship between core platysteirids
      and core vangids. Our biogeographic reconstruction somewhat unexpectedly suggests
      that the large African radiation of malaconotids originated after a single over
      water dispersal from Australasia around 45-33.7 mya, shedding new light on the
      origins of the Afrotropical avifauna.

PMID- 22475816
TI  - Analysis of malaria parasite phenotypes using experimental genetic crosses of
      Plasmodium falciparum.
AB  - We review the principles of linkage analysis of experimental genetic crosses and
      their application to Plasmodium falciparum. Three experimental genetic crosses
      have been performed using the human malaria parasite P. falciparum. Linkage
      analysis of the progeny of these crosses has been used to identify parasite genes
      important in phenotypes such as drug resistance, parasite growth and virulence,
      and transmission to mosquitoes. The construction and analysis of genetic maps has
      been used to characterise recombination rates across the parasite genome and to
      identify hotspots of recombination.

PMID- 22475818
TI  - Podocyte-specific overexpression of human angiotensin-converting enzyme 2
      attenuates diabetic nephropathy in mice.
AB  - Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin II to angiotensin-(1
      7) and is expressed in podocytes. Here we overexpressed ACE2 in podocytes in
      experimental diabetic nephropathy using transgenic methods where a nephrin
      promoter drove the expression of human ACE2. Glomeruli from these mice had
      significantly increased mRNA, protein, and activity of ACE2 compared to wild-type
      mice. Male mice were treated with streptozotocin to induce diabetes. After 16
      weeks, there was no significant difference in plasma glucose levels between wild
      type and transgenic diabetic mice. Urinary albumin was significantly increased in
      wild-type diabetic mice at 4 weeks, whereas albuminuria in transgenic diabetic
      mice did not differ from wild-type nondiabetic mice. However, this effect was
      transient and by 16 weeks both transgenic and nontransgenic diabetic mice had
      similar rates of proteinuria. Compared to wild-type diabetic mice, transgenic
      diabetic mice had an attenuated increase in mesangial area, decreased glomerular
      area, and a blunted decrease in nephrin expression. Podocyte numbers decreased in
      wild-type diabetic mice at 16 weeks, but were unaffected in transgenic diabetic
      mice. At 8 weeks, kidney cortical expression of transforming growth factor-beta1
      was significantly inhibited in transgenic diabetic mice as compared to wild-type
      diabetic mice. Thus, the podocyte-specific overexpression of human ACE2
      transiently attenuates the development of diabetic nephropathy.

PMID- 22475821
TI  - Predictors of parental posttraumatic stress disorder symptoms in the year after
      adolescent traumatic injury.
AB  - OBJECTIVES: Parental posttraumatic stress disorder (PTSD) is common after
      pediatric traumatic injury and may negatively impact parental functioning and
      quality of life during this key period of the child's early postinjury recovery.
      This study aimed to evaluate the course and predictors of PTSD in parents during
      the year after an adolescent traumatic injury. METHODS: This prospective cohort
      study included a population-based sample of 99 parent-adolescent dyads.
      Assessment was through structured interview administration of standardized
      measures. Interviews were conducted within 30 days of injury and 2, 5, and 12
      months after injury. Mixed model regression was used to evaluate variables
      potentially associated with repeated measures of parental PTSD symptoms at the
      follow-up time points. RESULTS: Twenty-three percent of parents met symptomatic
      criteria for PTSD at the first postinjury evaluation, as did 15% at 2 months, 7%
      at 5 months, and 6% at 12 months after the injury. The percentage of parents
      meeting symptomatic PTSD criteria decreased significantly between the 2-month and
      12-month evaluations. Mixed-model regression analyses revealed greater PTSD
      symptoms within 30 days of injury and a greater number of postinjury parental
      traumatic and/or stressful life events as significant predictors of parental
      PTSD. Adolescent factors did not affect the risk of parental PTSD. CONCLUSIONS: A
      substantial subgroup of parents demonstrate high PTSD symptom levels during the
      course of the year after an adolescent injury. Given that early modifiable risk
      factors can be identified, future investigations focusing on screening and
      intervention are warranted.

PMID- 22475819
TI  - Net endogenous acid production is associated with a faster decline in GFR in
      African Americans.
AB  - Increased acid excretion may promote renal injury. To evaluate this in African
      Americans with hypertensive nephrosclerosis, we studied the association between
      the net endogenous acid production and progression of kidney disease in 632
      patients in the AASK trial. Protein and potassium intakes were estimated from 24
      h urea nitrogen and potassium excretion, and used to estimate net endogenous acid
      production, averaged over 2 years, approximating routine intake. The link between
      net endogenous acid production and the I(125)iothalamate glomerular filtration
      rate (iGFR) and time to end-stage renal disease or doubling of serum creatinine
      was analyzed using mixed models and Cox proportional hazards regressions. The
      trend in higher net endogenous acid production was significantly associated with
      a faster decline in iGFR over a median of 3.2 years. After adjustment for age,
      body mass index, baseline iGFR, urine protein-to-creatinine ratio, and randomized
      treatment group, the trend in higher net endogenous acid production remained
      significantly associated with a faster decline in iGFR at a rate of 1.01 ml/min
      per 1.73 m(2) per year faster in the highest compared to the lowest quartile.
      However, in time-to-event analyses over a median of 7.7 years, the adjusted
      hazard ratio (1.10) for composite renal events per 25 mEq/day higher net
      endogenous acid production was not significant. Hence, our findings implicate
      endogenous acid production as a potential modifiable risk factor for progressive
      kidney disease.

PMID- 22475822
TI  - Application of photoactive yellow protein as a photoresponsive module for
      controlling hemolytic activity of staphylococcal alpha-hemolysin.
AB  - A chimeric protein (N-PYP-Hla), consisting of staphylococcal pore-forming toxin
      alpha-hemolysin (Hla) and photoactive yellow protein (PYP), exhibited
      photoresponsive hemolytic activities, where visible light irradiation gave rise
      to retardation of hemolysis at 25  degrees C.

PMID- 22475820
TI  - Transcription factor FoxO1, the dominant mediator of muscle wasting in chronic
      kidney disease, is inhibited by microRNA-486.
AB  - Chronic kidney disease (CKD) accelerates muscle protein degradation by
      stimulating the ubiquitin proteasome system through activation of the E3 ligases,
      Atrogin-1/MAFbx and MuRF-1. Forkhead transcription factors (FoxOs) can control
      the expression of these E3 ligases, but the contribution of individual FoxOs to
      muscle wasting is unclear. To study this we created mice with a muscle-specific
      FoxO1 deletion. The absence of FoxO1 blocked 70% of the increase in E3 ligase
      induction by CKD as well as the proteolysis and loss of muscle mass. Thus, FoxO1
      has a role in controlling ubiquitin proteasome system-related proteolysis. As
      microRNA (miR)-486 reportedly dampens FoxO1 expression and its activity,we
      transfected a miR-486 mimic into primary cultures of myotubes and found this
      blocked dexamethasone-stimulated protein degradation without influencing protein
      synthesis.It also decreased FoxO1 protein translation and increased FoxO1
      phosphorylation by downregulation of PTEN phosphatase, a negative regulator of p
      Akt. To test its efficacy in vivo, we electroporated miR-486 into muscles and
      found that the expression of the E3 ligases was suppressed and muscle mass
      increased despite CKD. Thus, FoxO1 is a dominant mediator of CKD-induced muscle
      wasting, and miR-486 coordinately decreases FoxO1 and PTEN to protect against
      this catabolic response.

PMID- 22475823
TI  - Anomalous enhancement in the infrared phonon intensity of a one-dimensional
      uneven peanut-shaped C60 polymer.
AB  - A one-dimensional (1D) uneven peanut-shaped C(60) polymer formed from electron
      beam (EB)-induced polymerization of C(60) molecules showed an anomalous increase
      in two characteristic infrared (IR) peak intensities, which are respectively due
      to the radial and tangential motion of the 1D polymer, when compared to the IR
      peaks of pristine C(60) films. This anomaly was analyzed on the basis of the
      vibrational van Hove singularity (VHS), using an extended thin-shell elastic
      model fully considering the effects of periodic radius modulation inherent to the
      1D uneven peanut-shaped C(60) polymer. We succeeded in explaining the enhancement
      in the tangential peak intensity by VHS, whereas the origin to cause that in the
      radial peak intensity is still unclear.

PMID- 22475825
TI  - Voices amplified.

PMID- 22475826
TI  - Developing a research network in environmental health for Latin America.

PMID- 22475827
TI  - Lessons from genome-wide association studies for epidemiology.

PMID- 22475828
TI  - Intuitions, simulations, theorems: the role and limits of methodology.

PMID- 22475829
TI  - Theorems, proofs, examples, and rules in the practice of epidemiology.

PMID- 22475830
TI  - Mediation analysis with multiple versions of the mediator.
AB  - The causal inference literature has provided definitions of direct and indirect
      effects based on counterfactuals that generalize the approach found in the social
      science literature. However, these definitions presuppose well-defined
      hypothetical interventions on the mediator. In many settings, there may be
      multiple ways to fix the mediator to a particular value, and these various
      hypothetical interventions may have very different implications for the outcome
      of interest. In this paper, we consider mediation analysis when multiple versions
      of the mediator are present. Specifically, we consider the problem of attempting
      to decompose a total effect of an exposure on an outcome into the portion through
      the intermediate and the portion through other pathways. We consider the setting
      in which there are multiple versions of the mediator but the investigator has
      access only to data on the particular measurement, not information on which
      version of the mediator may have brought that value about. We show that the
      quantity that is estimated as a natural indirect effect using only the available
      data does indeed have an interpretation as a particular type of mediated effect;
      however, the quantity estimated as a natural direct effect, in fact, captures
      both a true direct effect and an effect of the exposure on the outcome mediated
      through the effect of the version of the mediator that is not captured by the
      mediator measurement. The results are illustrated using 2 examples from the
      literature, one in which the versions of the mediator are unknown and another in
      which the mediator itself has been dichotomized.

PMID- 22475831
TI  - A conversation with Olli Miettinen. Interview by James A. Hanley.

PMID- 22475832
TI  - Recruiting researchers through Facebook.

PMID- 22475833
TI  - Benefits of publicly available data.

PMID- 22475834
TI  - On influencing population means.

PMID- 22475835
TI  - One in 16 quadrillion: importance of blinding in research reproducibility.

PMID- 22475837
TI  - Air pollution and stroke.

PMID- 22475836
TI  - Calcium, magnesium, and colorectal cancer.

PMID- 22475838
TI  - The impact of blood transfusion on short and long term prognosis in STEMI
      patients treated with primary percutaneous coronary intervention: a single center
      experience.

PMID- 22475839
TI  - A population-based follow-up study on the risk of acute myocardial infarction
      following adhesive capsulitis.

PMID- 22475840
TI  - Animal models of organic heart valve disease.
AB  - Heart valve disease is a frequently encountered pathology, related to high
      morbidity and mortality rates in industrialized and developing countries. Animal
      models are interesting to investigate the causality, but also underlying
      mechanisms and potential treatments of human valvular diseases. Recently, animal
      models of heart valve disease have been developed, which allow to investigate the
      pathophysiology, and to follow the progression and the potential regression of
      disease with therapeutics over time. The present review provides an overview of
      animal models of primary, organic heart valve disease: myxoid age-related,
      infectious, drug-induced, degenerative calcified, and mechanically induced
      valvular heart disease.

PMID- 22475841
TI  - Atrial fibrillation management, outcomes and predictors of stable disease in
      daily practice: prospective non-interventional study.
AB  - BACKGROUND: We aimed to describe the current management of patients with atrial
      fibrillation (AF) by cardiologists, and to identify predicting factors for a
      stable disease course. METHODS: 2753 consecutive patients with ECG-confirmed AF
      in the previous 12 months were documented in a 1-year observational (non
      interventional) study from 616 centers. Stable disease was defined as having
      neither AF related intervention nor change in antiarrhythmic therapy in the
      previous 12 months. Stepwise selection of parameters for multivariate regression
      was used to identify factors for stable AF. RESULTS: At baseline, paroxysmal AF
      was reported in 33.5%, persistent in 26.7%, and permanent in 39.7%; rate control
      alone was the prevailing antiarrhythmic strategy (64.2%). Drugs for
      thromboembolic prevention were administered in 93.8%, with a clear predominance
      of oral anticoagulants (OAC), alone or in combination with antiplatelet drugs.
      Electrical or pharmacological conversions were reported in 23.6%. A total of 96
      (3.5%) patients in the total cohort experienced stroke, 72 patients (2.6%) TIA,
      and 24 (0.9%) arterial embolism. 26% were hospitalized during follow-up (0.4
      events per patient), and 9.4% developed incident heart failure (42% prevalence at
      follow-up). The rate of stable patients was 43.4%. In the multivariate model male
      gender, history of stroke, and permanent (vs. persistent) AF were associated with
      stable disease. Conversely, the factors chronic heart failure, impaired left
      ventricular function, rhythm-control (vs. other), OAC and antiplatelet therapy
      were significantly correlated with unstable disease. CONCLUSIONS: The relatively
      low proportion of stable patients and in particular, the high hospitalization and
      stroke rate indicate difficulties in everyday management of patients with AF.

PMID- 22475842
TI  - Heart failure and atrial fibrillation--does practice meet the anticoagulation
      guidelines?

PMID- 22475843
TI  - Impact of right atrial pressure on decision-making using fractional flow reserve
      (FFR) in elective percutaneous intervention.
AB  - BACKGROUND: We undertook a prospective study to assess the impact of routine
      incorporation of right atrial pressure into the calculation of FFR in a real
      world elective PCI cohort. METHODS: 42 patients with stenoses in 2 separate
      epicardial vessels at coronary angiography were studied. Using a temperature and
      pressure sensing guidewire (TPSG) FFR and FFRRAP were performed in the target
      vessel pre and post PCI and in a non-target vessel. FFR was defined as Pd/Pa,
      FFRRAP as Pd-Pv/Pa-Pv where Pv was right atrial pressure and Pd/Pa were the
      hyperemic distal and proximal arterial pressures respectively. RESULTS: Mean RAP
      was 9.1 +/- 0.7 mmHg. Mean FFR was significantly lower when RAP was included in
      the calculation (FFRRAP 0.77 +/- 0.19 vs. FFR 0.80 +/- 0.16, p<0.001). In the
      target vessel pre PCI, incorporating RAP into the calculation of FFR resulted in
      a significant difference in the FFR value (FFR Pre-PCI 0.69 +/- 0.02 vs. FFRRAP
      Pre-PCI 0.63 +/- 0.03, p<0.0001). 21 patients had an FFR <= 0.8 in the group. If
      right atrial pressure were utilized to calculate FFR prior to PCI, an additional
      9 patients would have been re-categorised to an FFR <= 0.8. Following PCI, mean
      FFR was lower when RAP was incorporated (Post PCI FFRRAP 0.93+/-0.05 vs. Post PCI
      FFR 0.95 +/- 0.06, p<0.001). CONCLUSION: Incorporation of right atrial pressure
      into the calculation of FFR significantly alters FFR values and may potentially
      reclassify lesions below ischaemic thresholds.

PMID- 22475844
TI  - Totally occluded left main coronary presented with dizziness and temporary coma.

PMID- 22475845
TI  - Exposure to supernatants of macrophages that phagocytized dead mesenchymal stem
      cells improves hypoxic cardiomyocytes survival.
AB  - OBJECTIVE: To observe the impact of supernatants from macrophages that
      phagocytized dead MSCs (pMPhi) on the survival of hypoxic cardiomyocytes.
      METHODS: MSCs were isolated from bone marrow of mice and dead MSCs were harvested
      after 6h hypoxia. Macrophages were obtained from thioglycolate-elicited
      peritoneal cavity. Macrophages and dead MSCs were co-cultured for 2 days in the
      presence or absence of LPS (1 MUg/ml). Cardiomyocytes obtained from neonatal mice
      were exposed to various medium including supernatants from pMPhi. MTT cell
      proliferation assay and mitochondria membrane potential were used to evaluate the
      viability of cardiomyocytes. Cytokines and chemokines (TNF-alpha, IFN-gamma, IL
      6, IL-12, PGE2, VEGF-alpha, Ang-1, KGF, IGF-1, PDGF-BB, and EPO) in culture
      medium of macrophages, MSCs and pMPhi were detected by ELISA and Real-Time-PCR.
      RESULTS: phagocytic activity of macrophages to dMSC was significantly enhanced by
      LPS. PGE2, VEGF-alpha, Ang-1, KGF, IGF-1, PDGF-BB, and EPO levels were
      significantly increased in supernatants of pMPhi. Exposure to supernatants of
      pMPhi significantly improved viability and survival time of hypoxic
      cardiomyocytes. CONCLUSION: Exposure to supernatants of pMPhi significantly
      improved viability and survival time of hypoxic cardiomyocytes, which might be
      linked to increased cytokines and chemokines secretion by pMPhi.

PMID- 22475846
TI  - Obesity, health status, and 7-year mortality in percutaneous coronary
      intervention: in search of an explanation for the obesity paradox.
AB  - BACKGROUND: Obesity is a growing health problem and is associated with adverse
      outcomes in coronary artery disease (CAD). However, recent studies have shown
      better survival in cardiovascular patients with overweight or obesity, which has
      been referred to as the "obesity paradox". As there is no clear understanding of
      the phenomenon, we examined the association between body mass index (BMI) and all
      cause mortality in patients treated with percutaneous coronary intervention (PCI)
      at 7-year follow-up, and the potential role of health status in explaining the
      obesity paradox. METHODS: Consecutive PCI patients (72.5% men; mean age 62.0 +/-
      11.2 years, range [27-90]years) from the Rapamycin-Eluting Stent Evaluated at
      Rotterdam Cardiology Hospital (RESEARCH) registry completed the 36-item short
      form health survey (SF-36) to assess health status at baseline. Patients were
      classified into a normal weight, overweight or obesity group. RESULTS: The
      prevalence of normal weight was 34.7% (354/1019), overweight was seen in 45.9%
      (468/1019) of patients, and 19.3% (197/1019) was obese. After a median follow-up
      of 7.0 +/- 1.7 years, 163 deaths (16.0%) from any cause were recorded. Cumulative
      hazard functions differed significantly for the obese and overweight group when
      compared to the normal weight group (log-rank X(2)=6.59, p<0.05). In
      multivariable analysis, overweight, but not obesity, remained associated with a
      lower risk for all-cause mortality (HR=0.60, 95%CI [0.42-0.86], p=0.005).
      Additionally, after adding the 8 health status SF-36 domains to the multivariate
      model, the association between overweight and mortality remained unchanged.
      CONCLUSION: In our study population overweight, but not obesity, was associated
      with a lower risk for 7-year mortality in PCI patients. Health status as measured
      with the SF-36 did not seem to play a role in explaining the obesity paradox.

PMID- 22475847
TI  - Myocardial perfusion imaging with 13N-ammonia PET is a strong predictor for
      outcome.
AB  - BACKGROUND/OBJECTIVES: The aim of the present study was to assess the long-term
      predictive value of myocardial perfusion imaging (MPI) with (13)N-ammonia
      positron emission tomography (PET) in patients with suspected myocardial
      perfusion abnormality. At present, outcome data on the predictive value of MPI in
      (13)N-ammonia PET exist only for rather small patient populations. METHODS:
      Cardiac perfusion was assessed in 943 consecutive patients using (13)N-ammonia
      PET, and follow-up was obtained in 698 (74%). 77 patients who underwent early
      revascularization (<60 days) were excluded and 621 patients were assigned to
      normal versus abnormal perfusion for outcome analysis. Hard events (cardiac death
      and non-fatal myocardial infarction) and major adverse cardiac events (MACE; hard
      events, hospitalization for cardiac reasons and late revascularization) were
      investigated using the Kaplan-Meier method. Independent predictors for various
      cardiac events were identified using Cox proportional hazard regression analysis.
      RESULTS: During follow-up (5.7 +/- 2.5 years), 275 patients had at least 1
      cardiac event, including 102 cardiac deaths and 33 non-fatal myocardial
      infarction. Abnormal perfusion (n=469) was associated with a higher incidence of
      MACE (P<0.001) and hard events (P<0.001) throughout the 10-year follow-up period.
      CONCLUSIONS: Cardiac perfusion findings in (13)N-ammonia PET are strong
      predictors of long-term outcome.

PMID- 22475848
TI  - Beneficial effect of digitoxin for heart failure from noncompaction in myotonic
      dystrophy 1.

PMID- 22475849
TI  - Outbreak of meningococcal disease associated with an elementary school --
      Oklahoma, March 2010.
AB  - During March 10-31, 2010, the Oklahoma State Department of Health (OSDH)
      investigated an outbreak of meningococcal (Neisseria meningitidis) disease
      involving a consolidated school district of 1,850 students in rural northeastern
      Oklahoma. An OSDH field investigation team and the Rogers County Health
      Department (RCHD) established operations at the affected elementary school as
      soon as the outbreak was recognized. Five cases of meningococcal disease
      (including one probable case) were identified among four elementary school
      students and one high school student. Two students died; two recovered fully, and
      one survivor required amputation of all four limbs and facial reconstruction. All
      N. meningitidis isolates were serogroup C with the same multilocus sequence type
      and an indistinguishable pulsed-field gel electrophoresis pattern. To interrupt
      the outbreak, mass vaccination and chemoprophylaxis clinics were conducted in the
      population at risk; 1,459 vaccinations and 1,063 courses of antibiotics were
      administered. Children eligible for the Vaccines for Children (VFC) program
      received 1,092 of the vaccine doses, demonstrating that VFC is a feasible funding
      source for vaccine during an outbreak response.

PMID- 22475850
TI  - HIV, other STD, and pregnancy prevention education in public secondary schools --
      45 states, 2008-2010.
AB  - In the United States, 46% of high school students have had sexual intercourse and
      potentially are at risk for human immunodeficiency virus (HIV) infection, other
      sexually transmitted diseases (STDs), and pregnancy. The National HIV/AIDS
      Strategy for the United States recommends educating young persons about HIV
      before they begin engaging in behaviors that place them at risk for HIV
      infection. The Community Preventive Services Task Force (CPSTF) also recommends
      risk reduction interventions to prevent HIV, other STDs, and pregnancy among
      adolescents. To estimate changes in the percentage of secondary schools that
      teach specific HIV, other STD, and pregnancy risk reduction topics, a key
      intervention consistent with those supported by the National HIV/AIDS Strategy
      and CPSTF, CDC analyzed 2008 and 2010 School Health Profiles data for public
      secondary schools in 45 states. This report summarizes the results of those
      analyses, which indicated that in 2010, compared with 2008, the percentage of
      secondary schools teaching 11 topics on HIV, other STD, and pregnancy prevention
      in a required course in grades 6, 7, or 8 was significantly lower in 11 states
      and significantly higher in none; the percentage of secondary schools teaching
      eight topics in a required course in grades 9, 10, 11, or 12 was significantly
      lower in one state and significantly higher in two states; and the percentage of
      secondary schools teaching three condom-related topics in a required course in
      grades 9, 10, 11, or 12 was significantly lower in eight states and significantly
      higher in three states. Secondary schools can increase efforts to teach all age
      appropriate HIV, other STD, and pregnancy prevention topics to help reduce risk
      behaviors among students.

PMID- 22475851
TI  - Influenza outbreaks at two correctional facilities -- Maine, March 2011.
AB  - On March 8, 2011, the Maine Center for Disease Control and Prevention (Maine CDC)
      received a laboratory report of a positive influenza specimen from an intensive
      care unit patient who was an inmate at a prison (facility A). That same day, the
      state medical examiner notified Maine CDC of an inmate death suspected to be have
      been caused by influenza at another, nearby prison (facility B). On March 9,
      Correctional Medical Services (CMS), which provides health services to both
      facilities, notified Maine CDC that additional inmates and staff members from
      both facilities were ill with influenza-like illness (ILI). CMS reported that
      influenza vaccination coverage among inmates was very low (<10%), and coverage
      among staff members was unknown but believed to be low. Maine CDC assisted CMS
      and the Maine Department of Corrections (DOC) in conducting an epidemiologic
      investigation to gather more information about the two cases, initiate case
      finding, and implement control measures, which included emphasizing respiratory
      hygiene and cough etiquette, closing both facilities to new admissions and
      transfers, and offering vaccination and antiviral drugs to inmates and staff
      members. This report describes the public health response and highlights the
      importance of collaboration between public health and corrections officials to
      identify quickly and mitigate communicable disease outbreaks in these settings,
      where influenza can spread rapidly in a large and concentrated population.
      Correctional facilities should strongly consider implementing the following
      measures during each influenza season: 1) offering influenza vaccination to all
      inmates and staff members, 2) conducting education on respiratory etiquette, and
      3) making documentation regarding the vaccination status of inmates and staff
      members accessible.

PMID- 22475852
TI  - Biodiesel from lignocellulosic biomass--prospects and challenges.
AB  - Biodiesel can be a potential alternative to petroleum diesel, but its high
      production cost has impeded its commercialization in most parts of the world. One
      of the main drivers for the generation and use of biodiesel is energy security,
      because this fuel can be produced from locally available resources, thereby
      reducing the dependence on imported oil. Many countries are now trying to produce
      biodiesel from plant or vegetable oils. However, the consumption of large amounts
      of vegetable oils for biodiesel production could result in a shortage in edible
      oils and cause food prices to soar. Alternatively, the use of animal fat, used
      frying oils, and waste oils from restaurants as feedstock could be a good
      strategy to reduce the cost. However, these limited resources might not meet the
      increasing demand for clean, renewable fuels. Therefore, recent research has been
      focused the use of residual materials as renewable feedstock in order to lower
      the cost of producing biodiesel. Microbial oils or single cell oils (SCOs),
      produced by oleaginous microorganisms have been studied as promising alternatives
      to vegetable or seed oils. Various types of agro-industrial residues have been
      suggested as prospective nutritional sources for microbial cultures. Since the
      most abundant residue from agricultural crops is lignocellulosic biomass (LCB),
      this byproduct has been given top-priority consideration as a source of biomass
      for producing biodiesel. But the biological transformation of lignocellulosic
      materials is complicated due to their crystalline structure. So, pretreatment is
      required before they can be converted into fermentable sugar. This article
      compares and scrutinizes the extent to which various microbes can accumulate high
      levels of lipids as functions of the starting materials and the fermentation
      conditions. Also, the obstacles associated with the use of LCB are described,
      along with a potentially viable approach for overcoming the obstacles that
      currently preclude the commercial production of biodiesel from agricultural
      biomass.

PMID- 22475853
TI  - Sludge as dioxins suppressant in hospital waste incineration.
AB  - Nitrogen containing compounds such as ammonia, urea and amines can effectively
      inhibit the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs). Sewage sludge accumulates both sulfur and nitrogen during wastewater
      treatment so it could be used to reduce PCDD/Fs formation. Indeed, it is observed
      in this study that the gas evolving from the sludge drying process can
      significantly suppress chlorobenzene (CBz) and PCDD/Fs formation from fly ash
      collected from a hospital waste incinerator. For instance, the reduction of
      hexachlorobenzene (HxCBz) and PCDD/Fs amount was 92.1% and 78.7%, respectively,
      when the drying gas evolving from 2g sludge flew through 2g fly ash. These tests
      were conducted in the frame of projects devoted to hospital waste incineration.
      The disposal technology for hospital waste (HW), developed in this institute,
      features rotary kiln pyrolysis combined with post-combustion followed by flue gas
      cleaning. Hence, some preliminary tests were devoted to investigate dioxins
      suppression by co-pyrolysis and co-combustion of polyvinyl chloride (PVC) and
      sludge in lab scale. More experimental research will be conducted to
      appropriately assess these effects of sludge on PCDD/Fs emissions during co
      pyrolysis/combustion of HW and sludge.

PMID- 22475854
TI  - A novel fluorescent assay for sucrose transporters.
AB  - BACKGROUND: We have developed a novel assay based on the ability of type I
      sucrose uptake transporters (SUTs) to transport the fluorescent coumarin beta
      glucoside, esculin. Budding yeast (Saccharomyces cerevisiae) is routinely used
      for the heterologous expression of SUTs and does not take up esculin. RESULTS:
      When type I sucrose transporters StSUT1 from potato or AtSUC2 from Arabidopsis
      were expressed in yeast, the cells were able to take up esculin and became
      brightly fluorescent. We tested a variety of incubation times, esculin
      concentrations, and buffer pH values and found that for these transporters, a 1
      hr incubation at 0.1 to 1 mM esculin at pH 4.0 produced fluorescent cells that
      were easily distinguished from vector controls. Esculin uptake was assayed by
      several methods including fluorescence microscopy, spectrofluorometry and
      fluorescence-activiated cell sorting (FACS). Expression of the type II sucrose
      transporter OsSUT1 from rice did not result in increased esculin uptake under any
      conditions tested. Results were reproduced successfully in two distinct yeast
      strains, SEY6210 (an invertase mutant) and BY4742. CONCLUSIONS: The esculin
      uptake assay is rapid and sensitive and should be generally useful for
      preliminary tests of sucrose transporter function by heterologous expression in
      yeast. This assay is also suitable for selection of yeast showing esculin uptake
      activity using FACS.

PMID- 22475855
TI  - Cathodal stimulation of human MT+ leads to elevated fMRI signal: a tDCS-fMRI
      study.
AB  - PURPOSE: Transcranial direct current stimulation (tDCS) was reintroduced about a
      decade ago as a tool for inducing long-lasting changes in cortical excitability.
      Recently it has been shown that both motor and cognitive functions can be
      influenced by tDCS. Here, we tested the effect of tDCS on the blood-oxygen level
      dependent (BOLD) signal evoked by coherent visual motion using functional
      magnetic resonance imaging (fMRI). METHODS: The subjects underwent 10 min of
      cathodal and sham tDCS, applied over the right MT+. Following stimulation, random
      dot kinomatograms (RDK) with different percentages (10%, 30%, 50%) of coherently
      moving dots were presented. RESULTS: All motion stimuli activated MT+ in both
      stimulation conditions. However, cathodal stimulation led to an increase in fMRI
      signal in MT+ when compared to sham stimulation. This effect did not depend on
      the coherence level of the visual stimulus. CONCLUSIONS: Here, we show for the
      first time, that cathodal tDCS stimulation leads to elevated fMRI signal in the
      human visual cortex.

PMID- 22475856
TI  - Gait metric profile of 157 patients suffering from anterior knee pain. A
      controlled study.
AB  - PURPOSE: Gait metric alterations have been previously reported in patients
      suffering from anterior knee pain (AKP). Characterization of simple and
      measureable gait parameters in these patients may be valuable for assessing
      disease severity as well as for follow-up. Previous gait studies in this
      population have been comprised of relatively small cohorts and the findings of
      these studies are not uniform. The objective of the present study was to examine
      spatio-temporal gait parameters in patients with AKP in comparison to symptom
      free controls. Furthermore, the study aimed to examine the relationship between
      self-reported disease severity and the magnitude of gait abnormalities. METHODS:
      157 patients with AKP were identified and compared to 31 healthy controls.
      Patients were evaluated with a spatiotemporal gait analysis via a computerized
      mat, the Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire
      and the Short Form (SF)-36 health surveys. RESULTS: AKP patients walked with
      significantly lower velocity (15.9%) and cadence (5.9%), shorter step length
      (9.5%), stride length (9.6%), and showed significant differences in all gait
      cycle phases (P<0.05 for all). Study group reported higher levels of pain (96%),
      functional limitation (94%), and poorer perception of mental quality of life
      (30%) (P<0.05 for all). CONCLUSION: Significant differences were found between
      the spatiotemporal gait profile of AKP patients and symptom-free matched
      controls. In addition, an association was found between subjective disease
      severity and gait abnormalities. These findings suggest the usefulness of gait
      parameters, alongside with the use of self-evaluation questionnaires, in
      identifying deviations of these patients from healthy population.

PMID- 22475857
TI  - Comparative immunogenicity and safety of different multivalent component
      pertussis vaccine formulations and a 5-component acellular pertussis vaccine in
      infants and toddlers: a randomized, controlled, open-label, multicenter study.
AB  - BACKGROUND: Pentavalent and quadrivalent combination vaccine formulations from
      the same manufacturer (DTaP-IPV/Hib [PENTA], DTaP-IPV [QUAD]) were investigated
      as to whether they were sufficiently interchangeable to tailor use to local
      preference or availability. METHODS: A randomized, controlled, open-label, 4
      armed, multicenter study in healthy, full-term infants (42-89 days of age) was
      conducted in 38 centers across the United States. Participants were randomized
      1:1:1:1 to a control vaccine group (3 doses DTaP, IPV, and Hib and at Dose 4 DTaP
      and Hib) and 3 combination vaccine groups: (1) 3 doses PENTA, then Dose 4 DTaP
      and Hib; (2) 4 QUAD doses and Hib; (3) 4 PENTA doses. Participants (N=2167) were
      immunized at 2, 4, and 6 months of age, Dose 4 participants (N=1832) at 15 months
      of age. Immunogenicity was assessed before Doses 1 and 4 and after Doses 3 and 4.
      Safety was assessed 30 days after each dose and through 180 days Post-Dose 4.
      RESULTS: Antibody responses and geometric mean concentrations/geometric mean
      titers (GMCs/GMTs) elicited by each combination vaccine were noninferior (upper
      bound 90% confidence interval of GMC/GMT ratios <1.5) to control vaccines except
      pertactin GMCs were higher after 4 control DTaP doses (157.46 EU/mL) than after
      Dose 4 with DTaP and Hib (after a PENTA infant series) (111.70 EU/mL) and after 4
      PENTA doses (98.00 EU/mL). Fever rates in the combination vaccine groups were
      noninferior (upper bound 95% CI of combination vaccine group fever rate minus
      control vaccine group fever rate <10%) to the control vaccine group except the
      rate after 4 QUAD and Hib doses (23.5%) was higher than after 4 control DTaP
      doses (13.9%). CONCLUSIONS: PENTA and QUAD had similar safety profiles and no
      clinically important differences in immunogenicity compared with separately
      administered control vaccines. ClinicalTrials.gov (NCT ID: NCT00255047).

PMID- 22475858
TI  - Prevalence of Streptococcus pneumoniae serotypes causing invasive and non
      invasive disease in South East Asia: a review.
AB  - BACKGROUND: Streptococcus pneumoniae is a major cause of bacterial infections
      resulting in significant morbidity and mortality worldwide. Currently, up to 13
      serotypes are included in pneumococcal conjugate vaccines (PCVs). However, the
      serotype formulation of these vaccines was initially designed to protect children
      against serotypes most commonly causing invasive disease in North America, and
      may not reflect the serotype distribution across the world. Data regarding
      pneumococcal epidemiology from the other parts of the world, in particular South
      East Asia, has not been reviewed. METHODS: This systematic literature review
      analyses published serotype data regarding S. pneumoniae isolates from South East
      Asian countries (defined as countries belonging to the Association of South East
      Asian Nations, ASEAN): Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar,
      Philippines, Singapore, Thailand and Vietnam up to 3rd of March 2012. RESULTS:
      Analysis of data from six ASEAN countries, from which information on pneumococcal
      serotypes was available, showed that the most common disease causing serotypes
      (in rank order) were 19F, 23F, 14, 6B, 1, 19A and 3. Serotype distribution of
      pneumococcal isolates was similar across the ASEAN region. Serotype level data
      was more commonly reported for pneumococcal isolates causing invasive
      pneumococcal disease than for those from non-invasive disease. Studies from
      Malaysia, Thailand and Singapore contributed the largest proportion of
      pneumococcal isolates, and serotype data, when compared to other ASEAN countries.
      CONCLUSION: This review demonstrates that the majority of IPD causing serotypes
      in SE Asia are included in currently licensed PCVs. However, PCV's are included
      in the routine childhood immunisation schedule of only one of the ten countries
      included in this analysis. Our findings demonstrate the scarcity of information
      available on serotype prevalence and distribution of pneumococci in SE Asia.

PMID- 22475859
TI  - Predictors of administration and attitudes about pneumococcal, Haemophilus
      influenzae type b and rotavirus vaccines among pediatricians in India: a national
      survey.
AB  - INTRODUCTION: According to the World Health Organization in 2008, pneumonia
      accounted for 20% of deaths and diarrheal diseases accounted for 13% of deaths
      among children under 5 in India. Vaccines are available for Streptococcus
      pneumoniae (pneumococcal conjugate vaccine (PCV)), Haemophilus influenzae type b
      (Hib vaccine), and rotavirus. Barriers to including these vaccines in routine
      immunization schedule in India include potential negative impacts on fragile
      existing immunization programs and cost. Pediatricians who are members of the
      Indian Academy of Pediatrics (IAP) are important stakeholders for vaccine
      delivery and maintaining public confidence in vaccines. METHODS: A random sample
      of 785 pediatricians belonging to IAP was selected for the survey conducted from
      June 2009 to June 2010. Descriptive analyses using sampling weights were
      performed to evaluate the distributions of variables assessing vaccine-related
      attitudes and behaviors among pediatricians. Logistic regression was used to
      assess factors associated with routine vaccine use. RESULTS: The majority of
      pediatricians reported administering PCV (85.6%), Hib (95.9%), and rotavirus
      (80.2%) vaccine selectively or routinely. Pediatricians who had high perceived
      disease susceptibility were 2.42 times more likely to report routine
      administration of Hib vaccine (OR 2.42, 95% CI 1.24, 4.74). Pediatricians who had
      high perceived Hib vaccine efficacy were 4.74 times more likely to administer Hib
      vaccine routinely (OR 4.74, 95% CI 2.09, 10.74). Perceptions of disease
      susceptibility and severity or of vaccine safety and efficacy were not associated
      with routine administration of PCV or rotavirus vaccine. CONCLUSIONS:
      Understanding predictors of routine use of a new vaccine could help focus
      interventions to improve the routine use of other vaccines. The importance of
      perceived susceptibility to and severity of diseases caused by S. pneumoniae,
      Hib, and rotavirus and perceived efficacy and safety of the vaccines by
      pediatricians presents an opportunity to design strategies to build support for
      new vaccine introduction and may have important implications for national
      immunization policy in India.

PMID- 22475861
TI  - Leishmaniasis: vaccine candidates and perspectives.
AB  - Leishmania is a protozoan parasite and a causative agent of the various clinical
      forms of leishmaniasis. High cost, resistance and toxic side effects of
      traditional drugs entail identification and development of therapeutic
      alternatives. The sound understanding of parasite biology is key for identifying
      novel drug targets, that can induce the cell mediated immunity (mainly CD4+ and
      CD8+ IFN-gamma mediated responses) polarized towards a Th1 response. These
      aspects are important in designing a new vaccine along with the consideration of
      the candidates with respect to their ability to raise memory response in order to
      improve the vaccine performance. This review is an effort to identify molecules
      according to their homology with the host and their ability to be used as potent
      vaccine candidates.

PMID- 22475860
TI  - The expected emotional benefits of influenza vaccination strongly affect pre
      season intentions and subsequent vaccination among healthcare personnel.
AB  - BACKGROUND: The relative importance of different attitudes in predicting
      vaccination among healthcare personnel (HCP) is unclear. We hypothesized that HCP
      who feel at risk without vaccination or say they would regret not getting
      vaccinated would be more likely to get vaccinated than HCP who do not expect
      these emotional benefits. METHODS: A prospective cohort of 1544 HCP with direct
      patient care was enrolled from September 18 to December 18, 2010 at Scott & White
      Healthcare in Texas and Kaiser Permanente Northwest in Oregon and Washington. An
      Internet-based questionnaire assessed pre-season intention to be vaccinated and
      included 12 questions on attitudes about vaccination: single-item measures of
      perceived susceptibility and vaccine effectiveness, 5 items that were summed to
      form a concerns about vaccine scale, and 5 items summed to form an emotional
      benefits of vaccination scale. Influenza vaccination status for the 2010-2011
      season and for 5 prior seasons was confirmed by medical record extraction.
      RESULTS: There were significant differences between vaccinated and unvaccinated
      HCP on all attitude items; 72% of vaccinated HCP agreed that they "worry less
      about getting the flu" if vaccinated, compared to only 26% of the unvaccinated
      (odds ratio=7.4, 95% confidence interval=5.8-9.5). In a multivariate model, the
      emotional benefits scale was the strongest predictor of 2010-2011 seasonal
      influenza vaccination, after adjusting for other attitude measures, prior
      vaccination history, and pre-season intention to be vaccinated. The predictive
      value of the emotional benefits scale was strongest for HCP with low pre-season
      intention to be vaccinated, where HCP vaccine receipt was 15% versus 83% for
      those with low versus high scores on the emotional benefits scale. CONCLUSIONS:
      The expected emotional benefits of vaccination strongly affect seasonal influenza
      vaccination among HCP, even after taking into account other attitudes, pre-season
      intentions, and prior vaccination history. These attitudes are promising targets
      for future vaccination campaigns.

PMID- 22475862
TI  - Why did patients with cardiovascular disease in the Netherlands accept Q fever
      vaccination?
AB  - This study examines patient's reasons for accepting Q fever vaccination,
      including risk perception, feelings of doubt, social influence, information
      seeking behavior, preventive measures taken, and perceptions regarding received
      information and governmental action. Data was obtained from exit interviews
      conducted after Q fever vaccination, between January and April 2011. A total of
      413 patients with specific cardiovascular conditions in the Netherlands
      participated in exit interviews; 70% were older than 60 years. Most reported
      reasons for accepting Q fever vaccination were: "I am at an increased risk for
      developing (chronic) Q fever" (69%) and "my general practitioner recommends Q
      fever vaccination for me" (34%). The majority (86%) reported a high perceived
      severity of Q fever, and only 6% felt vulnerable to Q fever after vaccination.
      One-third had doubts about getting vaccinated, primarily related to fears of side
      effects and practical barriers. Fifty-two percent solicited advice from their
      social networks; of these, 67% reported influence on their vaccination decision.
      General practitioners and family were the most reported sources of advice. Thirty
      percent actively sought information about Q fever vaccination. Twenty-two percent
      of all respondents had taken other preventive measures, such as avoiding contact
      with goats and sheep (74%), and cancelling or postponing visits to Q fever
      affected areas (36%). Almost one-half of all respondents reported negative
      feelings regarding governmental action to control Q fever. Significant
      differences were observed regarding feelings of doubt, information-seeking
      behavior, perceived vulnerability, preventive measures taken, and perceptions
      regarding received information and governmental action regarding gender, age,
      educational level, and/or employment status. Vaccination decision-making may
      differ among socio-demographic subgroups. When preparing future vaccination
      campaigns, it is important to obtain greater insight into these differences and
      take these aspects into account in risk communication strategies by tailoring
      information to specific target groups.

PMID- 22475863
TI  - Comparative seroepidemiology of pertussis, diphtheria and poliovirus antibodies
      in Singapore: waning pertussis immunity in a highly immunized population and the
      need for adolescent booster doses.
AB  - BACKGROUND: We assessed the seroepidemiology of pertussis, diphtheria and
      poliovirus antibodies in a cohort of highly immunized children, together with the
      burden of these diseases in Singapore. METHODS: Hospital residual sera collected
      between August 2008 and July 2010 from 1200 children aged 1-17 years were tested
      for the prevalence of IgG antibodies against Bordetella pertussis, diphtheria
      toxoid, and all three poliovirus types by enzyme-linked immunosorbent assays.
      RESULTS: We found an overall seroprevalence of 99.4% (95% CI 98.8-99.7%) for
      diphtheria, and 92.3% (95% CI 90.6-93.6%) for poliomyelitis, along with no
      indigenous cases of these diseases since 1993. However, the seroprevalence for
      pertussis was 60.8% (95% CI 58.0-63.5%) only. Among the subjects who had
      completed three doses of pertussis vaccination by the age of 2 years (n=1092),
      the pertussis seroprevalence was 85.0% (95% CI 79.7-89.2%) in those who received
      the last vaccination within a year before the study, and it decreased to 75.0%
      (95% CI 64.5-83.2%) and 63.1% (95% CI 50.9-73.8%) in those who had the last
      vaccination 1 year and 2 years before the study, respectively. The seroprevalence
      remained at about 50% for those whose last pertussis vaccination was administered
      4 years and longer before the study. CONCLUSIONS: The high seroprevalence for
      poliomyelitis and diphtheria confer solid herd immunity to eliminate these
      diseases in Singapore. In contrast, immunity against pertussis waned considerably
      over time, and routine boosters should be given to adolescents to ensure
      sustained immunity against pertussis.

PMID- 22475864
TI  - Pre-vaccination immunity and immune responses to a cell culture-derived whole
      virus H1N1 vaccine are similar to a seasonal influenza vaccine.
AB  - BACKGROUND: Immune responses to novel pandemic influenza vaccines may be
      influenced by previous exposure to antigenically similar seasonal strains.
      METHODS: An open-label, randomized, phase I/II study was conducted to assess the
      immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1
      A/California/07/2009 vaccine. 408 subjects were stratified by age (18-59 and >60
      years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 MUg
      hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of
      seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1
      strain was assessed. RESULTS: A single vaccination with either dose induced
      substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition
      (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A
      single 7.5 MUg dose induced seroprotection rates of 86.9% in adults and 75.2% in
      elderly subjects. Two 7.5 MUg vaccinations induced seroprotection rates in adult
      and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response
      to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI
      and MN antibodies persisted for >= 6 months post-vaccination. Between 34% and 49%
      of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at
      baseline. Higher baseline HI titers were associated with receipt of the 2008-09
      or 2009-10 seasonal influenza vaccine. High baseline A/California/07/2009
      neutralizing antibody titers were also associated with high baseline titers
      against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was
      included in the seasonal vaccine from 2000-01 to 2006-07. Pre-adsorption with
      A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline
      titers in 55% of tested sera. The vaccine was well tolerated with low rates of
      fever. CONCLUSIONS: A whole-virus H1N1 A/California/07/2009 vaccine was safe and
      well tolerated and a single dose induced substantial immune responses similar to
      seasonal influenza vaccines, probably due to immunological priming by previous
      seasonal influenza vaccines or infections.

PMID- 22475865
TI  - Designing and creating a modularized synthetic pathway in cyanobacterium
      Synechocystis enables production of acetone from carbon dioxide.
AB  - Ketones are a class of important organic compounds. As the simplest ketone,
      acetone is widely used as solvents or precursors for industrial chemicals.
      Presently, million tonnes of acetone is produced worldwide annually, from
      petrochemical processes. Here we report a biotechnological process that can
      produce acetone from CO(2), by designing and creating a modularized synthetic
      pathway in engineered cyanobacterium Synechocystis sp. PCC 6803. The engineered
      Synechocystis cells are able to produce acetone (36.0 mgl(-1) culture medium)
      using CO(2) as the sole carbon source, thus opens the gateway for biosynthesis of
      ketones from CO(2).

PMID- 22475866
TI  - Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors
      based on pharmacokinetic property-driven optimization.
AB  - We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo
      efficacy. While trying to maintain consistent in vitro and in vivo biological
      activity, we initiated a pharmacokinetic property-driven optimization to improve
      the metabolic stability and permeability of inhibitor 6. A simple scaffold
      replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly
      improved metabolic stability (4% vs. 65% remaining). Further modification of the
      pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral
      bioavailability than 6. Importantly, compound 21j exhibits greater in vivo
      efficacy than does 6 and Alogliptin and is worthy of further development.

PMID- 22475867
TI  - The impact of intracoronary thrombus aspiration on STEMI outcomes.
AB  - BACKGROUND: Manual coronary thrombus aspiration was associated with improved
      outcomes of ST-elevation myocardial infarction (STEMI) patients. We aimed to
      evaluate the outcome of aspiration in a "real-world" setting of primary
      percutaneous coronary intervention (PPCI). METHODS AND MATERIALS: We analyzed the
      outcome of STEMI patients who underwent PPCI (initial Thrombolysis in Myocardial
      Infarction flow grade 0/1), comparing patients who underwent aspiration (ASP) to
      those who had standard (STD) therapy. Various subgroups outcomes were further
      analyzed. Clinical end points included mortality and major adverse cardiovascular
      events (MACE) at 30 days and at 1 year. RESULTS: One thousand thirty-five
      consecutive patients were included: 189 (18.26%) with ASP and 846 (81.74%) with
      STD. ASP patients were younger (58+/-12 vs. 61+/-13, P<.05) and had higher
      incidence of direct stenting compared to STD patients (34% vs. 16.7%, P<.05). No
      significant differences were noted in the outcome of ASP vs. STD at 30 days
      (mortality rate 4.2% vs. 4.5%, P=.9; MACE 6.9% vs. 9.8%, P=.2) and at 1 year
      (mortality rate 8.0% vs. 8.3%, P=.9; MACE 20.0% vs. 22.3%, P=.5). A significant
      advantage in favor of ASP was evident in patients with proximal culprit lesions,
      anterior infarcts, and right ventricular involvement. CONCLUSIONS: Although this
      was largely a negative study, when STEMI involved a large jeopardized myocardium,
      aspiration was associated with sustained improved clinical outcomes.

PMID- 22475868
TI  - Spontaneous coronary artery dissection: one entity with several therapeutic
      options.
AB  - Spontaneous coronary artery dissection is an unusual and a rare cause of acute
      coronary syndrome and sudden death with multiple predisposing factors. Prompt
      recognition is crucial for appropriate patient management, but specific
      guidelines for optimal treatment are lacking. We report four cases of women with
      spontaneous coronary artery dissection revealed by ST-segment elevation, three in
      women during postpartum and one case associated with a Marfan syndrome. Our cases
      span the different therapeutic options from medical treatment, stenting, to
      coronary artery bypass graft surgery.

PMID- 22475869
TI  - Nutritional Management of Phenylketonuria.
AB  - Phenylketonuria (PKU) is caused by deficient activity of the enzyme phenylalanine
      hydroxylase, needed to convert the essential amino acid (AA) phenylalanine (phe)
      to tyrosine. In order to prevent neurological damage, lifelong adherence to a low
      phe diet that is restricted in natural foods and requires ingestion of a phe-free
      AA formula to meet protein needs is required. The goal of nutritional management
      for those with PKU is to maintain plasma phe concentrations that support optimal
      growth, development, and mental functioning while providing a nutritionally
      complete diet. This paper reviews developing a lifelong dietary prescription for
      those with PKU, outcomes of nutritional management, compliance with the low-phe
      diet across the life cycle, and new options for nutritional management. An
      individualized dietary prescription is needed to meet nutrient requirements, and
      the adequacy of phe intake is monitored with assessment of blood phe levels.
      Elevated phe concentrations may occur due to illness, excessive or inadequate phe
      intake, or inadequate intake of AA formula. Although normal growth and
      development occurs with adherence to the low-phe diet, it is important to monitor
      vitamin, mineral and essential fatty acid status, especially in those who do not
      consume sufficient AA formula. Given the growing population of adults with PKU,
      further research is needed to understand the risks for developing osteoporosis
      and cardiovascular disease. There are promising new options to liberalize the
      diet and improve metabolic control such as tetrahydrobiopterin therapy or
      supplementation with large neutral AAs. Moreover, foods made with
      glycomacropeptide, an intact protein that contains minimal phe, improves the PKU
      diet by offering a palatable alternative to AA formula. In summary, continued
      efforts are needed to overcome the biggest challenge to living with PKU -
      lifelong adherence to the low-phe diet.

PMID- 22475870
TI  - N-(4-hydroxyphenyl)retinamide promotes apoptosis of resting and proliferating B
      cell chronic lymphocytic leukemia cells and potentiates fludarabine and ABT-737
      cytotoxicity.
AB  - The in vitro effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide
      (4HPR, fenretinide) on primary B-cell chronic lymphocytic leukemia (CLL) cells
      from previously untreated CLL patients were investigated. 4HPR promoted the
      intrinsic apoptotic pathway by reactive oxygen species (ROS) generation and was
      accompanied by drop of Mcl-1 protein expression. The latter was not attributable
      to transcriptional downregulation but to protein degradation mediated by jun N
      terminal kinase activation, and likely by NF-kB downregulation and Noxa
      upregulation. CLL cells stimulated in vitro with CD40L did not increase 4HPR
      chemoresistance if activation was accompanied by proliferation. Intra-patient
      analysis confirmed that the proliferating pool of CLL cells was more sensitive to
      the cytotoxic action of 4HPR than the activated but resting CLL subpopulation.
      The different 4HPR susceptibility of the two subpopulations was associated with
      higher Noxa expression in proliferating CLLs. Combination experiments revealed
      that 4HPR strongly potentiated ABT-737 cytotoxicity, especially in proliferating
      CLL cells that displayed amplified chemoresistance to ABT-737 alone. Synergic
      cytotoxicity was also demonstrated in combination with fludarabine, in both
      resting and stimulated CLL samples. This study entitles 4HPR to be assayed as a
      chemotherapeutic adjuvant for the treatment of CLL.

PMID- 22475871
TI  - SPARC is dispensable for murine hematopoiesis, despite its suspected
      pathophysiological role in 5q-myelodysplastic syndrome.

PMID- 22475872
TI  - Consensus guidelines for the conduct and reporting of clinical trials in systemic
      light-chain amyloidosis.
AB  - This manuscript summarizes the recommendations that emerged from the first
      Roundtable on Clinical Research in Immunoglobulin Light-chain Amyloidosis (AL), a
      meeting sponsored by the Amyloidosis Foundation (Clarkston, MI, USA) to develop a
      consensus of experts on a modern framework for clinical trial design and drug
      development in AL. Recent diagnostic and technical advances in AL, and updated
      consensus guidelines for assessing hematologic and organ responses, enable us to
      define study populations, appropriate end points, and other criteria for all
      phases of clinical research. This manuscript provides a framework for the design
      and conduct of systematic collaborative clinical research in AL to encourage more
      rapid testing of therapies and to expedite new drug development and approval.

PMID- 22475873
TI  - E2F4 plays a key role in Burkitt lymphoma tumorigenesis.
AB  - Sporadic Burkitt lymphoma (sBL) is a rapidly growing B-cell non-Hodgkin's
      lymphoma whose treatment requires highly aggressive therapies that often result
      severely toxic. Identification of proteins whose expression or function is
      deregulated in sBL and play a role in its formation could facilitate development
      of less toxic therapies. We have previously shown that E2F1 expression is
      deregulated in sBL. We have now investigated the mechanisms underlying E2F1
      deregulation and found that the E2F sites in its promoter fail to repress its
      transcriptional activity in BL cells and that the transcriptional repressor E2F4
      barely interacts with these sites. We also have found that E2F4 protein levels,
      but not those of its mRNA, are reduced in sBL cell lines relative to immortal B
      cell lines. E2F4 protein expression is also decreased in 24 of 26 sBL tumor
      samples from patients compared with control tissues. Our data demonstrate that
      enforced E2F4 expression in BL cells not only diminishes E2F1 levels, but also
      reduces selectively the tumorigenic properties and proliferation of BL cells,
      while increasing their accumulation in G(2)/M. Our results therefore point to
      E2F4 as a target for developing novel and less toxic treatments for sBL.

PMID- 22475874
TI  - Color signal information content and the eye of the beholder: a case study in the
      rhesus macaque.
AB  - Animal coloration has provided many classical examples of both natural and sexual
      selection. Methods to study color signals range from human assessment to models
      of receiver vision, with objective measurements commonly involving spectrometry
      or digital photography. However, signal assessment by a receiver is not objective
      but linked to receiver perception. Here, we use standardized digital photographs
      of female rhesus macaque (Macaca mulatta) face and hindquarter regions, combined
      with estimates of the timing of the female fertile phase, to assess how color
      varies with respect to this timing. We compare objective color measures (camera
      sensor responses) with models of rhesus vision (retinal receptor stimulation and
      visual discriminability). Due to differences in spectral separation between
      camera sensors and rhesus receptors, camera measures overestimated color
      variation and underestimated luminance variation compared with rhesus macaques.
      Consequently, objective digital camera measurements can produce statistically
      significant relationships that are probably undetectable to rhesus macaques, and
      hence biologically irrelevant, while missing variation in the measure that may be
      relevant. Discrimination modeling provided results that were most meaningful (as
      they were directly related to receiver perception) and were easiest to relate to
      underlying physiology. Further, this gave new insight into the function of such
      signals, revealing perceptually salient signal luminance changes outside of the
      fertile phase that could potentially enhance paternity confusion. Our study
      demonstrates how, even for species with similar visual systems to humans, models
      of vision may provide more accurate and meaningful information on the form and
      function of visual signals than objective color measures do.

PMID- 22475875
TI  - Kinetic resolution of 1-(1-alkynyl)cyclopropyl ketones by gold(I)-catalyzed
      asymmetric [4+3]cycloaddition with nitrones: scope, mechanism and applications.
AB  - Highly useful optically active 1-(1-alkynyl)cyclopropyl ketones can be
      efficiently obtained by the kinetic resolution of the easily available racemic
      ones under the catalysis of the chiral gold(I) species. Reaction scope and
      synthetic applications are also investigated.

PMID- 22475876
TI  - The two-word stage: motivated by linguistic or cognitive constraints?
AB  - Child development researchers often discuss a "two-word" stage during language
      acquisition. However, there is still debate over whether the existence of this
      stage reflects primarily cognitive or linguistic constraints. Analyses of
      longitudinal data from two Deaf children, Mei and Cal, not exposed to an
      accessible first language (American Sign Language - ASL) until the age of 6
      years, suggest that a linguistic constraint is observed when cognition is
      relatively spared. These older children acquiring a first language after delayed
      exposure exhibit aspects of a two-word stage of language development. Results
      from intelligence assessments, achievement tests, drawing tasks, and qualitative
      cognitive analyses show that Mei and Cal are at least of average intelligence and
      ability. However, results from language analyses clearly show differences from
      both age peers and younger native signers in the early two-word stage, providing
      new insights into the nature of this phase of language development.

PMID- 22475877
TI  - Reproducibility of the time to peak torque and the joint angle at peak torque on
      knee of young sportsmen on the isokinetic dynamometer.
AB  - BACKGROUND: Although peak torque has shown acceptable reproducibility, this may
      not be the case with two other often used parameters: time to peak torque (TPT)
      and the angle of peak torque (APT). Those two parameters should be used for the
      characterization of muscular adaptations in athletes. METHODS: The isokinetic
      performance of the knee extensors and flexors in both limbs was measured in 29
      male athletes. The experimental protocol consisted of three consecutive identical
      paradigms separated by 45 min breaks. Each test consisted of four maximal
      concentric efforts performed at 60 and 180 degrees /s. Reproducibility was
      quantified by the standard error measurement (SEM), the coefficient of variation
      (CV) and by means of intra-class correlation coefficients (ICCs) with the
      calculation of 6 forms of ICCs. RESULTS: Using ICC as the indicator of
      reproducibility, the correlations for TPT of both limbs showed a range of 0.51
      0.65 in extension and 0.50-0.63 in flexion. For APT, the values were 0.46-0.60
      and 0.51-0.81, respectively. In addition, the calculated standard error of
      measurement (SEM) and CV scores confirmed the low level of absolute
      reproducibility. CONCLUSIONS: Due to their low reproducibility, neither TPT nor
      APT can serve as independent isokinetic parameters of knee flexor and extensor
      performance. So, given its reproducibility level, TPT and APT should not be used
      for the characterization of muscular adaptations in athletes.

PMID- 22475878
TI  - Pain assessment in Charcot-Marie-Tooth (CMT) disease.
AB  - OBJECTIVE: The objective of our study was to describe and evaluate the prevalence
      of chronic pain in persons with Charcot-Marie-Tooth (CMT) disease during a
      multidisciplinary consultation at the Center of Reference for Neuromuscular
      Diseases. METHODOLOGY: This prospective study was conducted between 2008 and
      2010, it was a partnership between a Center of Reference for Neuromuscular
      Diseases (Centre de reference des maladies neuromusculaires [CRMD]) and a
      Department for the Assessment and Treatment of Pain (Departement d'evaluation et
      de traitement de la douleur [DETD]). The evaluation consisted in a complete
      assessment of each patient during the first multidisciplinary consultation, with
      a previously established diagnosis validated by genetic testing, by various
      specialists: neurologist, PM&R physician, pain management specialist and
      physiotherapist. The evaluation tools used were Visual Analogical Scale (VAS),
      Hospital Anxiety and Depression Scale (HAD), DN4 scale, Neuropathic Pain Symptom
      Inventory (NPSI) (if DN4>=4), Pain Questionnaire of Saint Antoine (QDSA) (if
      DN4<4), body representation to define the painful areas, Overall Neuropathy
      Limitations Scale (ONLS), Medical Research Council scale (MRC), Short
      Questionnaire on Pain (QCD), VAS during transfers, self-care, getting dressed and
      physiotherapy sessions and quantified use of analgesics. RESULTS: A total of 50
      patients were included (28 women, 22 men); two patients (one man and one woman)
      were discarded from the study because of missing pain assessment data. Mean age
      was 47years (R: 14-85), in average the symptoms had been present for the past
      20years (R: 0.3-68), most patients had little impairment, the mean MRC was 53 (R:
      36-60), with CMT1A being predominant (CMT1A: 76.9%, CMTX: 13.5%, CMT2: 5.8%,
      CMT4: 3.8%). It is noted that 65.4% of patients reported some pain with a mean
      duration of pain at 140months (R: 5-660). The mean VAS was 5.5 (R: 1-10), greater
      than 4 in 79.4% of cases, requiring the use of analgesics in 38.4% of cases (step
      1: 60%, step 2: 40% on the WHO pain relief ladder). The predominant location of
      the pain was distal, peripheral and symmetric (64.7%); furthermore the feet were
      affected in 80% of cases. DN4 was positive in 40.6% of painful patients. In 62.5%
      of the cases, the pain did not have an underlying mechanical origin. The
      emotional impact remained quite modest (HAD: A=8; D=5). Patients with CMT1A
      seemed less affected by pain (P=0.03). CONCLUSION: This original study describes
      the pain in patients with CMT disease during a primary multidisciplinary
      consultation. We see that in 66% of cases, patients do report some pain, this
      pain is usually moderate, preferentially located in the extremities and is
      symmetric. In 62.5% of cases, the pain has a neuromuscular origin with a positive
      DN4 in 50% of cases in this etiology. In our study, patients with CMT1A report
      less pain than patients with other CMT types. This disease being quite rare (rare
      disease), the number of patients did not allow us to bring up statistically
      significant results. The pain must be thoroughly screened for because of its
      frequency in persons with CMT.

PMID- 22475879
TI  - Isolation and identification of petromyzestrosterol, a polyhydroxysteroid from
      sexually mature male sea lamprey (Petromyzon marinus L.).
AB  - Petromyzestrosterol (1), a novel polyhydroxylated steroid, was identified from
      water conditioned with sexually mature male sea lamprey (Petromyzon marinus), a
      jawless vertebrate animal. Along with this novel steroid, two known steroids,
      7alpha,12alpha,24-trihydroxy-5alpha-cholan-3-one-24-sulfate (3k PZS) and
      7alpha,12alpha,24-trihydroxy-5alpha-cholan-24-sulfate (PZS), were isolated.
      Structures of these compounds were unequivocally established by spectroscopic
      analyses and by comparison with spectra of known compounds. Electro-olfactogram
      recordings (EOG) showed that 1 at nanomolar concentrations was stimulatory for
      the olfactory epithelium of adult females. 3k PZS, known to function as a male
      sex pheromone, was more stimulatory than 1 for the female olfactory epithelia.
      The concentration-response curve of 3k PZS was exponential in shape with steep
      slopes between 10(-10) and 10(-6) mol L(-1). The concentration-response curve for
      1 was shallower than that for 3k PZS.

PMID- 22475880
TI  - Intracranial dissection: incidence and long term endovascular treatment results
      of a not so rare disease.
AB  - OBJECTIVE: The objective of this communication was to study the incidence and
      course of ICD and the long term outcome of this severe disease. The second goal
      was to analyze the different endovascular treatment modalities according to their
      long term results. METHODS: It is a retrospective analysis of 14 patients with
      ICD admitted in a single center in two consecutive years, treated with
      endovascular procedures. Patients harbouring blister-like ruptured intracranial
      aneurysms were excluded from this study. RESULTS: In this case series, 12
      patients presented with subarachnoid hemorrhage (SAH) and 2 with brain stem
      symptoms. Mean age was 51 years and 13 patients were female. Six patients (43%)
      died and 8 (57%) survived with a mRS at 0-1. Mean follow up was 21 months.
      CONCLUSIONS: ICD as a cause of SAH seems to be more frequent than previously
      thought and usually has a severe course. It requires a high level of suspicion to
      diagnosis and specific endovascular treatment modalities are required for each
      location to ensure long term stability and change the poor prognosis.

PMID- 22475881
TI  - The value of posterior inferior cerebellar artery wall imaging.

PMID- 22475882
TI  - Rituximab for tumefactive inflammatory demyelination: a case report.

PMID- 22475883
TI  - Malignant transformation of supratentorial ganglioglioma.

PMID- 22475884
TI  - Good laboratory practices for biochemical genetic testing and newborn screening
      for inherited metabolic disorders.
AB  - Biochemical genetic testing and newborn screening are essential laboratory
      services for the screening, detection, diagnosis, and monitoring of inborn errors
      of metabolism or inherited metabolic disorders. Under the Clinical Laboratory
      Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is
      categorized on the basis of the level of testing complexity as either waived
      (i.e., from routine regulatory oversight) or nonwaived testing (which includes
      tests of moderate and high complexity). Laboratories that perform biochemical
      genetic testing are required by CLIA regulations to meet the general quality
      systems requirements for nonwaived testing and the personnel requirements for
      high-complexity testing. Laboratories that perform public health newborn
      screening are subject to the same CLIA regulations and applicable state
      requirements. As the number of inherited metabolic diseases that are included in
      state-based newborn screening programs continues to increase, ensuring the
      quality of performance and delivery of testing services remains a continuous
      challenge not only for public health laboratories and other newborn screening
      facilities but also for biochemical genetic testing laboratories. To help ensure
      the quality of laboratory testing, CDC collaborated with the Centers for Medicare
      & Medicaid Services, the Food and Drug Administration, the Health Resources and
      Services Administration, and the National Institutes of Health to develop
      guidelines for laboratories to meet CLIA requirements and apply additional
      quality assurance measures for these areas of genetic testing. This report
      provides recommendations for good laboratory practices that were developed based
      on recommendations from the Clinical Laboratory Improvement Advisory Committee,
      with additional input from the Secretary's Advisory Committee on Genetics,
      Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in
      Newborns and Children; and representatives of newborn screening laboratories. The
      recommended practices address the benefits of using a quality management system
      approach, factors to consider before introducing new tests, establishment and
      verification of test performance specifications, the total laboratory testing
      process (which consists of the preanalytic, analytic, and postanalytic phases),
      confidentiality of patient information and test results, and personnel
      qualifications and responsibilities for laboratory testing for inherited
      metabolic diseases. These recommendations are intended for laboratories that
      perform biochemical genetic testing to improve the quality of laboratory services
      and for newborn screening laboratories to ensure the quality of laboratory
      practices for inherited metabolic disorders. These recommendations also are
      intended as a resource for medical and public health professionals who evaluate
      laboratory practices, for users of laboratory services to facilitate their
      collaboration with newborn screening systems and use of biochemical genetic
      tests, and for standard-setting organizations and professional societies in
      developing future laboratory quality standards and practice recommendations. This
      report complements Good Laboratory Practices for Molecular Genetic Testing for
      Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular
      genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6])
      to provide guidance for ensuring and improving the quality of genetic laboratory
      services and public health outcomes. Future recommendations for additional areas
      of genetic testing will be considered on the basis of continued monitoring and
      evaluation of laboratory practices, technology advancements, and the development
      of laboratory standards and guidelines.

PMID- 22475885
TI  - Fatigue in adolescents.

PMID- 22475886
TI  - A highly sensitive, label-free gene sensor based on a single conducting polymer
      nanowire.
AB  - A prerequisite for exploiting sensing devices based on semiconductor nanowires is
      ultra-sensitive and selective direct electrical detection of biological and
      chemical species. Here, we constructed a transducer based on copolymer of
      poly(3,4,-ethylenedioxythiophene) (PEDOT) and carboxylic group functionalised
      PEDOT single nanowire in between gold electrodes, followed by covalent attachment
      of amino-modified probe oligonucleotide. The target ODNs specific to Homo sapiens
      Breast and ovarian cancer cells were detected at femtomolar concentration and
      incorporation of negative controls (non-complementary ODN) were clearly
      discriminated by the sensor. The ex situ measurements were performed by using two
      terminal device setup and the changes in the interface of the nanowire associated
      with the association or dissociation of ODNs were measured as change in
      resistance. In addition, in situ measurements were performed by utilizing
      scanning ion conductance microscopy to measure the change in resistance of probe
      modified nanowire upon addition of different concentration of target ODNs in
      presence of relevant buffer. The constructed, nano sensor showed highly sensitive
      concentration dependent resistance change.

PMID- 22475887
TI  - Nanovesicle-based bioelectronic nose platform mimicking human olfactory signal
      transduction.
AB  - We developed a nanovesicle-based bioelectronic nose (NBN) that could recognize a
      specific odorant and mimic the receptor-mediated signal transmission of human
      olfactory systems. To build an NBN, we combined a single-walled carbon nanotube
      based field effect transistor with cell-derived nanovesicles containing human
      olfactory receptors and calcium ion signal pathways. Importantly, the NBN took
      advantages of cell signal pathways for sensing signal amplification, enabling ~
      100 times better sensitivity than that of previous bioelectronic noses based on
      only olfactory receptor protein and carbon nanotube transistors. The NBN sensors
      exhibited a human-like selectivity with single-carbon-atomic resolution and a
      high sensitivity of 1 fM detection limit. Moreover, this sensor platform could
      mimic a receptor-meditated cellular signal transmission in live cells. This
      sensor platform can be utilized for the study of molecular recognition and
      biological processes occurring at cell membranes and also for various practical
      applications such as food screening and medical diagnostics.

PMID- 22475888
TI  - An open-label pilot study of aripiprazole for male and female veterans with
      chronic post-traumatic stress disorder who respond suboptimally to
      antidepressants.
AB  - Emerging data suggest that second-generation antipsychotics such as aripiprazole
      may be effective in the treatment of post-traumatic stress disorder (PTSD).
      However, few clinical trials have used aripiprazole in PTSD, and data are limited
      on its use in Veterans with PTSD. The objective of this pilot trial was to
      investigate the safety and efficacy of aripiprazole in Veterans with PTSD. Ten
      individuals (five men and five women) meeting the Diagnostic and statistical
      manual of mental disorders, 4th ed., PTSD criteria participated in this 12-week,
      open-label, flexibly dosed monotherapy trial. The dose range of aripiprazole was
      5-30 mg/day, titrated to tolerability and clinical response. The primary outcome
      measure was the Clinician-Administered PTSD Scale. Additional outcomes included
      the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale (Top-8), the
      Davidson Trauma Scale, the Positive and Negative Syndrome Scale, the Beck
      Depression Inventory-Fast Screen, and Clinical Global Impressions-Improvement.
      Eight participants completed the study, and aripiprazole was generally well
      tolerated and associated with a significant improvement in PTSD symptoms, as
      measured by the Clinician-Administered PTSD Scale (primary outcome measure) and
      by the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale, and the
      Davidson Trauma Scale. An improvement was also observed on all three Positive and
      Negative Syndrome Scale subscales and the Beck Depression Inventory-Fast Screen,
      and the average Clinical Global Impressions-Improvement ratings indicated that
      patients were 'much improved'. These promising initial results merit further
      investigation in a larger, randomized-controlled trial.

PMID- 22475889
TI  - Lu AA21004, a multimodal psychotropic agent, in the prevention of relapse in
      adult patients with generalized anxiety disorder.
AB  - The purpose of this study was to investigate the long-term maintenance of the
      efficacy of Lu AA21004 5 or 10 mg/day in the prevention of relapse in patients
      with generalized anxiety disorder (GAD). Patients (n = 687) with a primary
      diagnosis of GAD (DSM-IV criteria) and a baseline Hamilton Anxiety (HAM-A) total
      score of at least 20 underwent a 20-week, open-label Lu AA21004 treatment. In
      all, 459 patients responded and were randomized to 24-56 weeks of a double-blind
      treatment with Lu AA21004 (n = 229) or placebo (n = 230). The predefined primary
      efficacy endpoint was time to relapse (HAM-A total score >= 15) using a Cox
      model; the key secondary efficacy endpoint under multiplicity control was time to
      relapse for patients responding to treatment for at least 12 weeks. The primary
      analysis showed a statistically significant effect of Lu AA21004 relative to the
      placebo on the time to relapse of GAD, with a hazard ratio of 2.71 (P < 0.001).
      There was a statistically significant effect of Lu AA21004 in the stable
      responders (hazard ratio = 3.06, P < 0.001). Lu AA21004 was well tolerated, with
      withdrawal rates due to adverse events of 9% (open-label) and 3% (placebo) and 4%
      (Lu AA21004) in the double-blind period. In this study, Lu AA21004 5 or 10 mg/day
      was efficacious in preventing relapse and was well tolerated in the maintenance
      treatment of GAD.

PMID- 22475890
TI  - Role of 18F-FDG PET/CT in detecting recurrent gallbladder carcinoma.
AB  - AIM: The present study was aimed to determine the efficacy of integrated FDG
      PET/CT in patients with gallbladder cancer (GBC) with suspicion of recurrent
      disease. METHODS: A total of 49 patients (male: 15, female: 34; median age: 52.5
      years) with GBC underwent FDG PET/CT for suspected recurrence. A total of 62
      PET/CT scans were acquired. Criteria for detection by PET/CT were both a positive
      FDG uptake and the correct anatomic localization of the tumor. The PET/CT
      findings were grouped as locoregional disease and metastatic disease. Results of
      PET/CT were compared with clinical and radiologic follow-up and/or
      histopathology. Sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy were calculated. Results of PET/CT were also
      compared with conventional imaging (CI) whenever available. RESULTS: Of 62
      PET/CT, 43 (69.4%) were positive and 19 (30.6%) were negative for recurrence. Of
      43 positive scans, 41 were true positive and 2 were false positive. Among 19
      negative PET/CT scans, 18 were true negative and 1 was false negative. PET/CT
      showed a sensitivity of 97.6% and specificity of 90% in detecting tumor
      recurrence. The positive predictive value, negative predictive value, and
      accuracy were 95.3%, 94.7%, and 95.1%, respectively. Locoregional disease was
      seen in 16 (37.2%) PET/CT studies, distant metastases were seen in 13 (30.2%),
      and 14 (32.5%) studies showed both locoregional disease and metastasis. When
      comparable CI was available, PET/CT showed a better specificity than CI for
      detection of recurrence. CONCLUSIONS: Integrated FDG PET/CT can detect recurrence
      in GBC with high sensitivity and specificity. Routine use of PET/CT in these
      patients will detect recurrence early and change the subsequent management.

PMID- 22475891
TI  - Accuracy of 18F-FDG PET/CT for diagnosing inguinal lymph node involvement in
      penile squamous cell carcinoma: systematic review and meta-analysis of the
      literature.
AB  - PURPOSE: Metastatic involvement of the inguinal lymph nodes is associated with
      decreased survival and is a strong prognostic factor in penile squamous cell
      carcinoma. The aim of the current systematic review was to evaluate the accuracy
      of (18)F-FDG PET/CT for inguinal lymph node staging in penile squamous cell
      carcinoma and possible influential factors. MATERIALS AND METHODS: Medline,
      SCOPUS, Springer, Science Direct, and Google Scholar were searched using the key
      words "(penile or penis) and PET," with no date or language limitation. The
      meeting abstracts were not excluded either. Statistical pooling was performed
      using the random-effects model. RESULTS: Seven studies were included in the meta
      analysis. One article had 2 different subgroups of patients, and each subgroup
      was considered as a separate study. Pooled sensitivity and specificity were 80.9%
      (95% confidence interval [CI]: 69.5%-89.4%) and 92.4% (95% CI: 86.8%-96.2%),
      respectively. Pooled sensitivity was 96.4% (95% CI: 81.7%-99.9%) for cN+ and
      56.5% (95% CI: 34.5%-76.8%) for cN0 patients. CONCLUSIONS: (18)F-FDG PET/CT
      imaging has relatively low sensitivity (especially in cN0 patients) for detection
      of inguinal lymph node involvement in penile cancer patients, which does not
      justify its routine use. However, patients with clinically palpable lymph nodes
      may benefit from (18)F-FDG PET/CT because the sensitivity in this subgroup of
      patients is high.

PMID- 22475892
TI  - Predictive value of metabolic tumor volume measured by 18F-FDG PET for regional
      lymph node status in patients with esophageal cancer.
AB  - OBJECTIVE: The aim of the current study was to investigate the predictive value
      of metabolic tumor volume (MTV) measured by (18)F-FDG PET/CT for regional lymph
      node (rLN) metastasis in patients with esophageal cancer. METHODS: A
      retrospective review identified 54 patients with surgically resected esophageal
      cancer who received (18)F-FDG PET/CT at diagnosis of cancer. The (18)F-FDG PET/CT
      findings for all primary cancer and rLN involvement were compared with the
      pathologic diagnosis within 5 weeks after surgical resection. The pathologic
      diagnoses of rLN state were confirmed by surgical resection. Univariate and
      multivariate analyses were used to analyze the associations among the pathologic
      rLN status and age, sex, T stage, location, differentiation, maximum standardized
      uptake value (SUV(max)), MTV2.5, and MTV3. RESULTS: The rLN(+) group showed
      statistically significant higher value of SUVmax than the rLN(-) group (P =
      0.0011). The rLN(+) group showed statistically significant higher value of MTV2.5
      (P = 0.0004) and MTV3 (P = 0.0005) than the rLN(-) group. In receiver operating
      characteristic analysis, the SUV(max), MTV2.5, and MTV3 did not show the
      statistical differences for the prediction of pathologic rLN involvement in
      esophageal cancer. In univariate analysis, T stage, SUV(max), MTV2.5, and MTV3
      were factors significantly associated with pathologic rLN involvement. However,
      in multivariate analysis, the MTV2.5 and MTV3 were factors significantly
      associated with pathologic rLN involvement in esophageal cancer. CONCLUSION:
      Based on the presented results, the MTV measured by (18)F- FDG PET/CT is a useful
      method for the prediction of pathologic rLN status in esophageal cancer patients.
      Further studies are needed to confirm these results and improve statistical
      accuracy.

PMID- 22475893
TI  - The relationship between GLUT-1 and vascular endothelial growth factor expression
      and 18F-FDG uptake in esophageal squamous cell cancer patients.
AB  - PURPOSE: To examine the relationship between glucose transporter-1 (GLUT-1) and
      vascular endothelial growth factor (VEGF) expression and (18)F-FDG uptake in
      esophageal squamous cell cancer patients. MATERIALS AND METHODS: Fifty-seven
      patients (52 male and 5 female) were included in this study. (18)F-FDG PET/CT was
      performed prior to the surgery. Immunohistochemistry was performed using
      postoperative histopathological specimens. The estimation of immunohistochemistry
      was conducted using scoring analysis. We investigated the correlations between
      maximum standardized uptake value (SUV(max)) and GLUT-1/VEGF
      expressions/pathologic tumor length (p-tumor length), and the relationships
      between pathologic T (p-T) stage and GLUT-1/VEGF expressions/SUV(max) and between
      lymph node metastasis (p-N) stage and GLUT-1/VEGF expressions/SUV(max). RESULTS:
      SUV(max) significantly correlated with GLUT-1 expressions and p-tumor length
      (GLUT-1: r = 0.475, P < 0.001; p-tumor length: r = 0.475, P < 0.001). SUV(max) of
      the primary tumor had a significant relationship with p-T stage, p-N stage, and
      VEGF expression (p-T stage: P < 0.001; p-N stage: P = 0.037; VEGF expression: P =
      0.009). There was a statistically significant difference between GLUT-1
      expression and p-T stage/VEGF expression, but not p-N stage (p-T stage: P =
      0.012; VEGF expression: P = 0.01; p-N stage: P = 0.572). VEGF expression had a
      significant relationship with p-T stage, but not with p-N stage (p-T stage: P =
      0.032; p-N stage: P = 0.763). CONCLUSION: (18)F-FDG uptake can be determined by
      GLUT-1 and VEGF. SUV(max) would have a connection with the tumor progression and
      lymph node metastasis.

PMID- 22475894
TI  - 18F-FDG PET/CT and contrast-enhanced CT in a one-stop diagnostic procedure: a
      better strategy for management of patients suffering from retroperitoneal
      fibrosis?
AB  - PURPOSE: Effective management of patients affected by retroperitoneal fibrosis
      (RPF) is an important issue because of lack of relevant parameters to objectively
      assess the degree of inflammation. We evaluated added value of contrast-enhanced
      computed tomography (CE-CT) combined with fluorine-18 fluorodeoxyglucose positron
      emission tomography (FDG PET) as a one-stop diagnostic procedure for the
      assessment and follow-up of patients with RPF. MATERIALS AND METHODS: (18)F-FDG
      PET and CE-CT findings were reviewed in 10 patients suffering from RPF. Maximum
      standard uptake values (on native and contrast-enhanced [ESUV(max)] CT) were
      calculated. Dimensions of periaortitis were measured on CT scans. Observed
      clinical changes between baseline PET scan (T0) and at 6 months follow-up (T6)
      were analyzed regarding differences of initial values for clinic and paraclinic
      parameters. RESULTS: Patients still suffering from pain 6 months after baseline
      PET scan had initially higher FDG uptake (ESUV(max): 5.7 +/- 0.9 vs. 2.4 +/- 0.9,
      P < 0.01). Unlike biologic and CT parameters, FDG uptake was the most relevant
      parameter to measure severity of inflammation (ESUV(max) threshold: 4.3; Se = Sp
      = 1.0). CE-CT exclusively allowed better delineation and more accurate assessment
      of FDG uptake of periaortitis and its extension to adjacent structures.
      CONCLUSIONS: Our results clearly show the usefulness of PET/CT for better
      evaluation and management of patients with fibroblast proliferation disease.
      Accurate determination of inflammation level is significantly improved when
      PET/CT and CE-CT are performed in the same study and used for better delineation
      of areas of residual inflammation.

PMID- 22475895
TI  - 18F-FDG retention index and biologic prognostic parameters in breast cancer.
AB  - AIM: To analyze the correlation between [(18)F]-fluoro-2-deoxy-D-glucose (F-FDG)
      uptake assessed by positron emission tomography/computed tomography (PET/CT) in
      breast tumors and histopathologic and immunohistochemical prognostic factors.
      MATERIAL AND METHODS: Sixty-eight women with breast cancer were prospectively
      evaluated. PET/CT was requested in the initial staging previous to neoadjuvant
      chemotherapy (multicentric study).All the patients underwent a standard (18)F-FDG
      PET/CT followed by a delayed acquisition, 1 hour (PET-1) and 3 hours (PET-2)
      after FDG administration. Both examinations were evaluated qualitatively and
      semiquantitatively (SUV(max) values) in PET-1 (SUV-1) and in PET-2 (SUV-2). The
      percentage variation of the standard uptake values (retention index) between PET
      1 and PET-2 was calculated.Clinical and metabolic stages were assessed according
      to TNM classification. All biologic prognostic parameters, such as the receptor
      status, p53 and c-erbB-2 expression, proliferation rate (Ki-67), and grading were
      determined from tissue of the primary tumor. Metabolic, clinical, and biologic
      parameters were correlated. RESULTS: A positive relationship was found between
      the SUV(max), tumor size, clinical, and metabolic stages. SUV-1 and SUV-2 values
      showed significant statistical correlation (P < 0.05) with PET stage and tumor
      size assessed by PET. On the contrary, the retention index showed relation with
      clinical stage (P < 0.05).When related to the biologic parameters, retention
      index showed the best results, with positive and significant relation (P < 0.05),
      with histologic grade, and Ki-67 and c-erbB-2 expression. Isolated SUV values
      only showed significant relation to Ki-67 expression. CONCLUSION: The retention
      index showed the best relation with biologic and clinical parameters compared
      with isolated SUVmax values for what could be a predictive marker of tumor
      biologic behavior.

PMID- 22475896
TI  - Tumor marker-guided PET in breast cancer patients-a recipe for a perfect wedding:
      a systematic literature review and meta-analysis.
AB  - INTRODUCTION: Early detection of breast cancer (BC) recurrence is a fundamental
      issue during follow-up. Although the utilization of new therapeutic protocols
      aimed at reducing the recurrence risk is defined, the diagnostic approach for
      early detection remains to be clarified. We aim to provide a critical overview of
      recently published reports and perform a meta-analysis on the use of tumor
      markers in BC patients as a guide for fluorodeoxyglucose positron emission
      tomography (PET) imaging. METHODS: Medline and Google Scholar were used for
      searching English and non-English articles that evaluate the role of PET in BC
      recurrence when an increase in tumor markers is found. All complete studies were
      reviewed; thus, quantitative and qualitative analyses were performed. RESULTS:
      From 2001 to May 2011, we found 19 complete articles that critically evaluated
      the role of PET in BC recurrence detection in the presence of elevated tumor
      markers. The meta-analysis of the 13 studies provided the following results:
      pooled sensitivity 0.878 (95% CI: 0.838-0.909), pooled specificity 0.693 (95% CI:
      0.553-0.805), and pooled accuracy 0.828 (95% CI: 0.762-0.878). CONCLUSIONS: The
      current experience confirms the potential of fluorodeoxyglucose PET, and in
      particular of PET/CT, in detecting occult soft tissue and bone metastases in the
      presence of a progressive increase of serum tumor markers in BC patients, but
      this should be better defined in the current practical recommendations.

PMID- 22475897
TI  - FDG PET/CT and diffusion-weighted imaging of head and neck squamous cell
      carcinoma: comparison of prognostic significance between primary tumor
      standardized uptake value and apparent diffusion coefficient.
AB  - PURPOSE: To compare primary tumor (18)F-fluorodeoxyglucose (FDG) maximum
      standardized uptake value (SUV(max)) and diffusion-weighted imaging (DWI)
      apparent diffusion coefficient (ADC) obtained in the same patients with head and
      neck squamous cell carcinoma (HNSCC) to clarify the prognostic significance of
      both indexes. MATERIALS AND METHODS: The study population comprised 26 patients
      with HNSCC visible on both pretreatment FDG PET/CT and DWI. Correlation between
      SUV(max) and ADC (b values; 0 and 800 seconds/mm(2)) was analyzed by the
      Spearman's rank test. Disease-free survival (DFS) was calculated by the Kaplan
      Meier method. Prognostic significance was assessed by the long-rank test and Cox
      proportional hazards analysis. RESULTS: SUV(max) and ADC correlated significantly
      and negatively (rho = -0.566, P = 0.005). High (>12.1) SUV(max) (P < 0.001), low
      (<= 0.88) ADC (P = 0.009), high (T3-4) T stage (P = 0.030), and high (N2-3) N
      stage (P = 0.007) were significant in predicting poor 2-year DFS. The accuracy
      for predicting disease events was 81% (21/26) for SUV(max) (>12.1) and 73%
      (19/26) for ADC(<= 0.88) without significant difference between them (P = 0.52).
      Disease event hazards ratios for significant unadjusted SUV(max) (P = 0.015) and
      ADC (P = 0.039) remained significant when adjusted for other dichotomized
      clinical covariates (SUV(max); P = 0.009-0.039, ADC; P = 0.017-0.037) except
      SUV(max) for ADC and ADC for SUV(max) and T stage. CONCLUSION: These results
      suggest that pretreatment primary tumor SUV(max) and ADC correlate significantly
      and negatively and both may have similar potential to predict DFS or disease
      events of HNSCC.

PMID- 22475898
TI  - Communicating in organizations, part III: important conversations for leaders.
AB  - Building excellent relationships with a large number of other people, avoiding
      CEO disease, encouraging positive thinking and innovation, using language from
      the edge, and effectively dealing with conflict and change are all critically
      important for leaders. All of these require excellent communication skills.

PMID- 22475899
TI  - Malignant transformation of retroperitoneal inflammatory pseudotumor to
      undifferentiated high-grade pleomorphic sarcoma on FDG PET/CT.
AB  - We report FDG PET/CT appearance of malignant transformation of retroperitoneal
      inflammatory pseudotumor to pleomorphic sarcoma in a 78-year-old woman. The
      patient was diagnosed with left retroperitoneal pseudotumor in 2007. She
      subsequently suffered from recurrent disease and chronic osteomyelitis in the L5
      vertebral body in July 2008, status post surgical excision. In November 2009,
      after the patient developed left groin pain, MRI study of lumbosacral spine and
      whole-body PET/CT study demonstrated 2 hypermetabolic soft-tissue masses
      originating from the L5 surgical bed. These masses were subsequently resected and
      were consistent with pleomorphic sarcoma. Malignant transformation of
      retroperitoneal pseudotumor to pleomorphic sarcoma is extremely rare.

PMID- 22475900
TI  - 18F-FDG PET/CT imaging of Sister Mary Joseph's nodule.
AB  - An 82-year-old woman was followed up for an uterine cervical adenocarcinoma
      treated by surgery. A whole-body fluorodeoxyglucose positron emission tomography
      study revealed a pathologic fluorodeoxyglucose uptake located in the umbilicus
      associated to peritoneal carcinomatosis. Biopsy of the umbilical nodule
      demonstrated an umbilical metastasis from the uterine adenocarcinoma, the so
      called "Sister Mary Joseph's nodule."

PMID- 22475901
TI  - FDG PET/CT of a late-term pregnant woman with breast cancer.
AB  - A 38-year-old pregnant woman at 26-week gestation with left breast cancer
      requested an FDG PET/CT scan for more detailed staging of her breast cancer
      before treatment. After discussing the potential radiation-related risk and
      estimating possible absorbed dose to fetus, she consented for examination. By
      using a low-radiation-dose CT protocol and administration of routine 370-MBq FDG
      without diuresis, the resultant calculated (using existing models to predict
      fetal radiation exposure) fetal dose from CT and FDG would be 3.60 mGy and 6.29
      mGy, respectively. In contrast to the existing few literatures, our case also
      demonstrated previously unreported uptake in the fetal kidneys.

PMID- 22475902
TI  - 18F-FDG PET/CT in a recurrent diffuse malignant peritoneal mesothelioma.
AB  - Peritoneal mesothelioma is a rare and aggressive tumor. Early diagnosis of the
      disease is difficult, delaying effective treatment. We report a case of
      recurrent, biphasic, diffuse, malignant peritoneal mesothelioma. Initial
      abdominal computed tomography showed abnormal but nonspecific findings suggestive
      of an ovarian malignancy, with a negative endoscopy and laboratory studies. An
      abdominal exploratory laparotomy found widespread malignancy within the
      peritoneum with a pathological diagnosis of peritoneal mesothelioma. A PET/CT
      imaging showed diffusely increased metabolic activity throughout the peritoneum,
      with no evidence of thoracic or pleural involvement. This case demonstrates the
      PET/CT findings seen with malignant recurrent peritoneal mesothelioma.

PMID- 22475903
TI  - The characteristics of FDG PET/CT imaging in pulmonary Langerhans cell sarcoma.
AB  - A 53-year-old man, who was a heavy smoker, presented with recent severe cough.
      Radiography demonstrated a large pulmonary mass in the right upper lung. FDG
      PET/CT demonstrated heterogeneous high-grade activity in the pulmonary mass
      located in the right upper lung (standardized uptake value of 20), with central
      necrosis, bilateral upper mediastinal lymphadenopathy, right supraclavicular
      lymphadenopathy, direct left sternal manubrium invasion, and distal bilateral
      peripheral lung metastasis. Histology revealed significant malignant cytologic
      features and CD1a- and S-100-positive cells by immunohistochemistry staining,
      typical for Langerhans cell sarcoma.

PMID- 22475904
TI  - 18F-FDG PET/CT in evaluation of radiofrequency ablation of liver metastasis.
AB  - Image-guided radiofrequency ablation (RFA) is a minimally invasive therapy option
      in the treatment of primary and secondary hepatic malignancies, which are not
      suitable for surgery/chemotherapy, and more recently, for tumors with limited
      hepatic involvement and solitary liver metastasis. Accurate assessment of
      treatment response after RFA remains a concern. Conventional imaging modalities
      have limitations of differentiation between residual/recurrence from post-RFA
      changes. We illustrate images of 3 patients in whom (18)F-FDG PET/CT was used for
      response assessment and restaging after RFA in liver tumors.

PMID- 22475905
TI  - Polymyalgia rheumatica and interspinous FDG uptake on PET/CT.
AB  - Polymyalgia rheumatica (PMR) is an inflammatory disease with macrophage
      infiltration and CD4+ T-lymphocytes-related mild synovitis commonly causing neck,
      shoulder, and hip stiffness in patients older than 50 years. Closely related to
      giant cell arthritis (GCA), PMR symptoms can be similar to rheumatoid arthritis.
      Erythrocyte sedimentation rate and C-reactive protein levels are elevated in >90%
      of cases. In 4 patients with PMR, (18)F-fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG PET/CT) demonstrates uptake in the shoulder
      and hip joints and also interspinous and supraspinous focal and diffuse uptake.
      We propose diffuse uptake may reflect ligament inflammation with focal uptake in
      adjacent interspinous bursitis.

PMID- 22475906
TI  - Occult colon cancer with initial cutaneous metastatic manifestation: PET/CT
      detection.
AB  - Skin metastasis as initial clinical presentation of occult internal organ
      malignancy is of rare occurrence, predominantly encountered in breast and lung
      cancer. The search for the occult causative primary malignancy is usually
      difficult with conventional anatomy-based cross-sectional imaging. The authors
      present a case of cecal cancer with thoracic and abdominal cutaneous metastasis
      demonstrated by PET/CT.

PMID- 22475907
TI  - False positive 18F-FDG PET/CT due to inflamed concha bullosa.
AB  - A 62-year-old woman with a history of breast cancer was referred for an (18)F-FDG
      PET/CT scan. She had an active upper respiratory infection at the time of
      examination. An FDG avid (SUV(max) = 7.7) middle turbinate was identified,
      correlating with an inflamed concha bullosa. A short review of concha bullosa is
      given.

PMID- 22475908
TI  - Q Fever masquerading as prostate cancer metastases.
AB  - We report a case of Q fever demonstrated on (99m)Tc methylene diphosphonate bone
      scan and fluorodeoxyglucose (FDG) PET/CT. A 66-year-old man with newly diagnosed,
      low-grade prostate cancer presented with abdominal and bone pain. Bone scan
      revealed multiple lesions suspicious for prostate cancer metastases. Because of
      liver abnormalities on noncontrast CT, an FDG PET/CT was performed and
      demonstrated FDG-avid sclerotic bone lesions, infiltrative liver disease, and
      retroperitoneal adenopathy. This appearance, thought unusual for low-grade
      prostate cancer, prompted extensive clinical evaluation for several months. Liver
      and iliac bone biopsies showed noncaseating granulomas without neoplasia.
      Extensive serologic evaluation eventually demonstrated elevated Q fever titers.

PMID- 22475909
TI  - Intense FDG activity in the brown adipose tissue in omental and mesenteric
      regions in a patient with malignant pheochromocytoma.
AB  - A 39-year-old man who had a history of surgical excision of left adrenal
      pheochromocytoma 3 years ago underwent an FDG PET/CT scan to evaluate possible
      metastatic/recurrent disease. In addition to multiple FDG-avid lesions typical of
      hypermetabolic malignant disease and the FDG uptake in regions rich in brown
      adipose tissue, there was also intense FDG activity in the omental and mesenteric
      regions, which are not common locations of elevated FDG activity. On the repeat
      FDG PET/CT scan 3 days later after the patient was prepared with propranolol, the
      omental and mesenteric FDG activity was diminished.

PMID- 22475910
TI  - Conjunctival lymphoma can be detected by FDG PET.
AB  - Four consecutive patients presented with extranodal marginal zone B-cell lymphoma
      of mucosa-associated lymphoid tissue (MALT lymphoma) in the conjunctiva. After
      the initial resection, long-term follow-up without additional therapy showed the
      clinical relapse. Fluorodeoxyglucose positron emission tomography fused with
      computed tomography (PET/CT) showed abnormal uptake in the conjunctival relapsed
      lesions, which were, on reresection, again proven as MALT lymphoma. Small and
      thin lesions of MALT lymphoma in the conjunctiva can be detected by
      fluorodeoxyglucose PET/CT. The resolution of PET/CT, delineated in this study,
      could be applied to the other areas of the body to achieve more accurate staging
      of lymphoma.

PMID- 22475911
TI  - Bilateral breast uptake demonstrated on FDG PET/CT scans in 3 male patients with
      hepatocellular carcinomas.
AB  - We reported 3 male patients with hepatocellular carcinoma who underwent FDG
      PET/CT for systemic survey before liver transplantation. All of their scans
      demonstrated obvious FDG uptake in bilateral breasts. These uptakes might be
      owing to gynecomastia caused by an increase in free estrogen related to the
      cirrhotic liver.

PMID- 22475912
TI  - A case of primary pericardial mesothelioma detected by 18F-FDG PET/CT.
AB  - Primary pericardial mesothelioma is an extremely rare malignancy. We report a
      case of a 58-year-old woman who presented with fever and fatigue. She had no
      apparent history of occupational or incidental exposure to asbestos. A
      postcontrast-enhanced chest CT revealed a 77 * 56-mm mass lesion in the
      pericardium. The FDG PET/CT was carried out, which demonstrated an intense FDG
      uptake to a main pericardial tumor and disseminated lesions in the pericardium.
      Histologic examination confirmed the primary malignant pericardial mesothelioma.

PMID- 22475913
TI  - Bilateral ovarian metastases from gastric carcinoma on FDG PET/CT.
AB  - We report PET/CT appearance of bilateral ovarian metastases in a 63-year-old
      female patient with newly diagnosed poorly differentiated adenocarcinoma of the
      stomach. She was also found to have peritoneal metastasis on an outside CT study.
      Staging PET/CT demonstrates not only the hypermetabolic gastric primary tumor and
      peritoneal disease but also bilateral enlarged, moderately active ovaries. The
      patient subsequently underwent biopsies of bilateral ovaries which revealed
      metastatic disease from primary gastric carcinoma. It is important to consider
      this form of neoplasm in the differential diagnosis because the treatment and
      prognosis will be different from a dyssynchronous primary tumor.

PMID- 22475914
TI  - Colon cancer metastatic to a urachus diagnosed by PET/CT.
AB  - A 50-year-old man presented with a mass in the transverse colon diagnosed by
      colonoscopy. He underwent a left hemicolectomy and was diagnosed with a
      moderately differentiated adenocarcinoma penetrating into the pericolic adipose
      but no lymph node metastases. His course was uneventful with enrollment in a
      monoclonal antibody research treatment protocol. Eight years later, he presented
      with hematuria. A PET/CT demonstrated a hypermetabolic right external iliac lymph
      node and a hypermetabolic mass within a urachal remnant. The mass was excised and
      pathologically proven to represent a metastasis from the original primary tumor.

PMID- 22475915
TI  - Current readings in nuclear medicine.

PMID- 22475916
TI  - A very rare case of nonfunctioning pituitary adenoma incidentally disclosed at
      18F-FDG PET/CT.
AB  - This is a case of a 48-year-old man treated with surgery and (131)I for papillary
      thyroid carcinoma: a follow-up (18)F-FDG PET/CT incidentally evidenced pituitary
      uptake, also seen in (111)In-octreoscan as increased uptake in the sellar area.
      MRI confirmed a pituitary mass. The patient did not show any signs or symptoms
      related to this lesion; 1 year later, both PET/CT and MRI findings remained
      unchanged. Surgery confirmed nonfunctioning benign pituitary adenoma. This single
      case observed in 12,873 consecutive patients scanned in our center confirms the
      possibility that nonfunctioning benign pituitary adenomas may be FDG-avid: uptake
      mechanisms remain unknown, and targeted studies are needed.

PMID- 22475917
TI  - Postorchiectomy intrascrotal hematoma mimicking local recurrence on 18F-FDG
      PET/CT: a diagnostic dilemma.
AB  - Intratesticular hematomas usually develop immediately after orchiectomy is done
      for testicular tumors and may last for 3 to 6 weeks or longer. They may be
      confused with local recurrence on clinical examination and imaging. We present
      the (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed
      tomography (PET/CT) images of a 30-year-old man who underwent right radical
      transinguinal orchiectomy for seminoma. PET/CT done 8 weeks after orchiectomy
      revealed a soft tissue lesion in the right scrotum with increased FDG uptake,
      suspicious for local recurrence. However, on color Doppler ultrasonography of the
      scrotum, the mass was confirmed to be a hematoma.

PMID- 22475918
TI  - Earlier detection of bone metastases from pleomorphic liposarcoma in a pediatric
      patient by FDG PET/CT than planar 99mTc MDP bone scan.
AB  - Bone scintigraphy using (99m)TC MDP (technetium-99m methylene diphosphonate) is a
      routine procedure for evaluation of osteoblastic metastases; however, its
      sensitivity compared with FDG PET/CT in a variety of malignancies remains to be
      established. We report a case of multiple osseous metastases revealed by FDG
      PET/CT in an 8-year-old girl with pleomorphic liposarcoma. Many of these osseous
      lesions were not visualized on the MDP planar bone scintigraphy performed 24
      hours after PET/CT scan, becoming evident only on repeat bone scan performed 3
      months later. The case suggests that FDG PET/CT has higher sensitivity in
      detecting osteoblastic metastases in pleomorphic liposarcoma.

PMID- 22475919
TI  - Intermittent cystocele diagnosed on 18F-FDG PET/CT scan.
AB  - A 78-year-old woman was diagnosed with stage III diffuse large B-cell lymphoma,
      and treated with chemotherapy in 2004. Imaging follow-up was performed by serial
      6-month diagnostic PET/CT scans. A PET/CT scan performed in June 2011 showed an
      unusual hourglass appearance of activity in the pelvis that prompted further
      investigation. Retrospective review of the prior diagnostic PET/CT scans revealed
      that the patient had a sliding bladder, located either above or below the
      pubococcygeal line at different imaging times, but during this scan, the bladder
      was "caught" moving up to its normal position.

PMID- 22475920
TI  - Atlas of sodium fluoride PET bone scans: atlas of NaF PET bone scans.
AB  - Sodium fluoride (NaF) is a bone-seeking positron-emitting tracer with high
      sensitivity and specificity for detection of osseous lesions, particularly
      osteolytic lesions. We believe that NaF positron emission tomography
      (PET)/computed tomography (CT) scans can provide a more thorough and conclusive
      evaluation of bone diseases than conventional Technetium-99m-methylene
      diphosphonate bone scans. Understanding both normal and pathologic patterns is
      important for the evaluation and interpretation of these studies. Thus, an atlas
      of NaF positron emission tomography/computed tomography bone scans demonstrating
      benign, pathologic, and malignant osseous lesions as well as extraosseous lesions
      will be invaluable in the correct interpretation and diagnosis of osseous
      lesions.

PMID- 22475921
TI  - Incarcerated inguinal hernia from metastatic pleural mesothelioma: PET/CT
      imaging.
AB  - PET/CT provides a comprehensive staging, post-therapeutic surveillance, and
      outcome prognosis of malignant pleural mesothelioma based on its hypermetabolic
      behavior. This ability of PET may allow the monitoring, prediction, and detection
      of uncommon distant gastrointestinal clinical manifestations of this disease. The
      authors present a case of PET/CT imaging of pleural mesothelioma disseminating to
      the abdomen and pelvis, inducing an incarcerated inguinal hernia.

PMID- 22475922
TI  - Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a
      case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation
      secondary to catecholamine-secreting pheochromocytoma?
AB  - Fused positron emission tomography-computed tomography (PET/CT) technology has
      enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is
      observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential
      source of false-positive interpretations for PET. The typical locations of BAT
      include neck, supraclavicular area, mediastinum, and paravertebral intercostal
      spaces. Examples of atypical locations for BAT include posterior neck, left
      paratracheal area, axillae, perirenal area, and retrocrural area. We report
      PET/CT findings in a young male patient with malignant retroperitoneal extra
      adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple
      locations including mesenteric BAT. We also propose catecholamine-secreting
      pheochromocytoma as a possible cause of BAT activation in our case.

PMID- 22475923
TI  - FDG uptake in sacroiliac joint due to osteitis condensans ilii shown on PET/CT in
      a patient with breast cancer: the value of coregistered CT in avoiding
      misinterpretation.
AB  - A 56-year-old woman with breast cancer underwent FDG PET/CT at follow-up. The PET
      images showed increased FDG uptake along right sacroiliac joint. The coregistered
      CT images showed diffuse sclerosis around the sacroiliac joints, but no bony
      destruction, periarticular erosion, or joint space narrowing. She had been
      complaining of intermittent lower back pain since her last pregnancy. The
      radiologic pictures and history of postpartum back pain were considered as
      typical characteristics for osteitis condensans ilii. This case reminds us that
      careful inspection of the coregistered CT images is important to avoid potential
      misinterpretation because of osteitis condensans ilii.

PMID- 22475924
TI  - Percutaneous biopsy based on PET/CT findings in cancer patients: technique,
      indications, and results.
AB  - OBJECTIVE: To describe a technique for CT-guided biopsy based on PET/CT findings
      and to evaluate the indications and results of the technique in cancer patients.
      METHODS: We evaluated all patients receiving CT-guided percutaneous biopsies
      whose indication was based on PET/CT findings at an oncology reference center
      from October 2009 to December 2010. The PET/CT images were evaluated side by side
      with noncontrast CT images to identify the lesion or area of interest to be
      biopsied. Biopsies were guided by CT with the needle directed at the area of
      metabolic activity identified in the PET/CT examination performed before the
      procedure. RESULTS: A total of 64 cases were included in this study. The most
      common lesion location was pulmonary (n = 28; 43.8%). The median of the lesions'
      greatest diameter and maximum SUV were 44.1 +/- 31.6 mm (10-186 mm) and 8.4 +/-
      5.9 (2.1-34.0), respectively. The histologic results of the biopsies were
      negative for malignancy in 15 cases (23.4%), positive in 46 cases (71.9%), and
      inconclusive in 3 cases (4.7%). Lesions with an SUV >= 4.0 were more likely to be
      malignant (85.4% vs. 46.2%; P = 0.006). CONCLUSIONS: CT-guided biopsies should be
      used routinely for lesions identified or better characterized by PET/CT. The
      results of this study demonstrate that this method is reliable, secure, and very
      accurate diagnostically, revealing a high percentage of malignant lesions.

PMID- 22475925
TI  - Squamous papilloma of the oral cavity and oropharynx on 18F-FDG PET/CT imaging.
AB  - Squamous papilloma is one of the most common benign neoplasms of the oral cavity
      and oropharynx. The (18)F-FDG PET/CT metabolic phenotype of this entity has not
      been described. We document the incidental finding of a hypermetabolic lesion at
      the right base of the tongue on an FDG PET/CT that proved to be squamous
      papilloma. The maximum standard uptake value was high at 7.0 g/ml. We conclude
      that oral cavity squamous papilloma can present with an intensely hypermetabolic
      phenotype on (18)F- FDG PET/CT. This benign entity should be included in the
      differential diagnosis of FDG-positive oral and oropharyngeal lesions.

PMID- 22475926
TI  - Synthesis and biological evaluation of isoxazolo[4,5-d]pyridazin-4-(5H)-one
      analogues as potent anti-inflammatory agents.
AB  - In this study, eighteen new isoxazolo[4,5-d]pyridazin-4(5H)-one derivatives
      possessing either a 1,3,4-thiadiazole or a 1,2,4-triazole-5-thione moiety were
      synthesized and tested for anti-inflammatory activity in vitro (COX-1/COX-2, 5
      LOX) and in vivo (rat paw edema assay). Compounds 15, 16, 25, 26 and 28-30 showed
      dual COX-2 (IC(50)'s in the 2.1-10.9 MUM range), and 5-LOX (IC(50)'s in the 6.3
      63.5 MUM range) inhibitory activity. When administered orally to rats, dual COX
      2/5-LOX inhibitors showed higher anti-inflammatory activity in vivo (30-45%
      reduction of the inflammatory response) than the reference drug ibuprofen (18%).
      Among dual COX-2/5-LOX inhibitors, the most potent compound (28) exhibited the
      best anti-inflammatory profile by inhibiting both COX-2 (IC(50)=2.1 MUM) and 5
      LOX (IC(50)=6.3 MUM) enzymes. We investigated the binding interactions of
      compound 28 by an enzyme-ligand molecular modeling (docking) studies, which
      showed favorable binding interactions in both COX-2 and 5-LOX active sites.
      Furthermore, the dual acting COX-2/5-LOX compound 28 exhibited a superior
      gastrointestinal safety profile (ulcer index=0.25) compared to the reference drug
      ibuprofen (UI=7.0) when administered orally at the same molar dose. These
      observations suggest that isoxazolo[4,5-d]pyridazin-4(5H)-one analogs represent a
      new scaffold to design potent, effective, and safe anti-inflammatory agents
      possessing dual COX-2/5-LOX inhibitory activity.

PMID- 22475927
TI  - Identifying questions in the American Association of Swine Veterinarian's PRRS
      risk assessment survey that are important for retrospectively classifying swine
      herds according to whether they reported clinical PRRS outbreaks in the previous
      3 years.
AB  - The American Association of Swine Veterinarian's (AASV) Production Animal Disease
      Risk Assessment Program (PADRAP) is a web-based program that offers a set of risk
      assessment surveys being used by veterinarians who are members of the AASV.
      Members use PADRAP to help producers systematically assess risk factors that may
      be associated with clinical outcomes. As assessments are performed the completed
      surveys are added to the dataset maintained at the Iowa State University College
      of Veterinary Medicine. One of the surveys included in PADRAP is the porcine
      reproductive and respiratory syndrome (PRRS) Risk Assessment for the Breeding
      Herd. The aim of the study was to categorize questions in version 2 of the PRRS
      Risk Assessment for the Breeding Herd survey as important or unimportant for
      classifying herds according to whether they reported clinical PRRS outbreaks in
      the previous 3 years. The results elucidate the relative importance of risk
      factors and areas of risk factors for clinical outcomes and removing unimportant
      questions may reduce the time required to complete the survey without affecting
      the quality of information obtained. Surveys from 896 sow herd sites in the
      United States and Canada completed between March 2005 and March 2009 were
      included in the analysis. The survey contained a large number of questions with a
      complex correlation structure among the questions. Responses for several
      questions were dependent upon responses to others. To address these issues, an
      approach was developed using a series of statistical methods including random
      forest, principle component analysis, logistic regression and receiver operating
      characteristic (ROC) analysis to classify the herds using the questions in the
      survey as explanatory variables. Questions were ranked by importance and
      systematically excluded from least important to most important. The questions
      excluded, without significantly affecting the performance of the model for
      classifying herds were identified as unimportant. Thirty-eight of the 127
      questions analyzed were identified as unimportant for classifying herds according
      to whether they reported clinical PRRS outbreaks in the previous 3 years.
      Sections of the survey where a large number of questions were identified as
      unimportant included (1) entry of semen into the breeding herd and (2)
      transportation of live animals. Sections with a high percentage of questions
      identified as unimportant included (1) characteristics of the site, (2) disposal
      of dead animals and waste management and (3) employee and visitors.

PMID- 22475928
TI  - Tumorigenesis: Cut here for differentiation.

PMID- 22475931
TI  - Assessment of reproductive toxicity under REACH.
AB  - The European REACH regulation requires the evaluation of reproductive toxicity in
      screening tests according to OECD TG 421 and 422 for substances above the tonnage
      level of 10 tons/year. The overall aim of this paper is to increase flexibility
      in combination with a reduced number of experimental animals. Therefore, in
      contrast to the existing approach the registrant should have the possibility to
      file a dossier for a substance at the level of 10 tons/year and above also on the
      basis of data from a developmental toxicity study (OECD TG 414) plus a full-scale
      subacute toxicity study (OECD TG 407 according to the 1995 protocol). The
      proposed new test strategy takes into account overall considerations of duty of
      care and animal welfare. It enables an assessment of developmental toxicity on a
      definitive instead of a screening level. Registrants should be allowed to select
      between these two options, either the existing approach (OECD TG 421/407 and
      alternatively TG 422) or the approach proposed in this paper (OECD TG 407 plus TG
      414).

PMID- 22475930
TI  - Cancer imaging by optical coherence tomography: preclinical progress and clinical
      potential.
AB  - The past decade has seen dramatic technological advances in the field of optical
      coherence tomography (OCT) imaging. These advances have driven commercialization
      and clinical adoption in ophthalmology, cardiology and gastrointestinal cancer
      screening. Recently, an array of OCT-based imaging tools that have been developed
      for preclinical intravital cancer imaging applications has yielded exciting new
      capabilities to probe and to monitor cancer progression and response in vivo.
      Here, we review these results, forecast the future of OCT for preclinical cancer
      imaging and discuss its exciting potential to translate to the clinic as a tool
      for monitoring cancer therapy.

PMID- 22475929
TI  - From genes to drugs: targeted strategies for melanoma.
AB  - The past decade has revealed that melanoma is comprised of multiple subclasses
      that can be categorized on the basis of key features, including the clinical
      stage of disease, the oncogenic molecular 'drivers', the anatomical location or
      the behaviour of the primary lesion and the expression of specific biomarkers.
      Although exercises in subclassification are not new in oncology, progress in this
      area has produced both conceptual and clinical breakthroughs, which, for
      melanoma, are unprecedented in the modern history of the disease. This Review
      focuses on these recent striking advances in the strategy of molecularly targeted
      approaches to the therapy of melanoma in humans.

PMID- 22475932
TI  - Hydrogen bond dynamics in the excited states: photodissociation of phenol in
      clusters.
AB  - We have investigated the photodynamics of phenol molecules in clusters. Possible
      reaction pathways following the photoexcitation of hydrogen-bonded phenol
      clusters have been identified theoretically using ab initio calculations.
      Experimentally we have studied the phenol molecules and clusters of various size
      distributions in a molecular beam apparatus. In particular, we have measured the
      H-fragment kinetic energy distributions after the excitation with 243 nm and 193
      nm laser radiation. At 243 nm the KED spectra did not show any significant
      difference between the photodissociation of isolated molecules and phenol in
      larger clusters, while at 193 nm the contribution of the fast H-fragments is
      significantly suppressed in clusters with respect to the bare phenol molecule. We
      have interpreted the experimental results within the framework of the suggested
      reaction pathways.

PMID- 22475933
TI  - Protective effect of ellagic acid (EA) on micronucleus formation induced by N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG) in mammalian cells, in in vitro assays
      and in vivo.
AB  - The beneficial effects of fruits and vegetables with respect to age-related
      diseases such as diabetes, atherosclerosis and several types of cancer are widely
      recognized and confirmed by several epidemiological studies. A possible approach
      for evaluating the protective potential of promising diet constituents is to
      evaluate their beneficial effect with respect to a set of biomarkers that are
      indicative of a potential risk for developing degenerative diseases. Among the
      numerous biomarkers of the effect of food-related carcinogens and for the
      assessment of the degree of risk for disease, chromosomal damage detection is
      very predictive. The aim of this study was to test antigenotoxic effect of
      ellagic acid (EA) both in in vitro and in vivo studies, in combination with N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG), a methylating agent. EA, a naturally
      occurring and widely distributed plant phenol, has been intensively studied but
      with conflicting results, depending on the endpoints considered and the
      experimental material employed. In vitro and in vivo studies differ in their
      experimental schedule: in the in vitro study pre- and post-treatments and
      simultaneous treatments with EA were performed, while in the in vivo study only
      pre-treatment was carried out. The results of this study clearly demonstrate a
      protective action of EA with respect to MNNG-induced micronuclei and cell
      proliferation both in vitro and in vivo. The lack of effect in the post-treatment
      in in vitro experiments excludes a possible effect of EA on DNA-repair systems.
      On the other hand, consumption of EA can have a protective action against primary
      DNA damage induced by oxidative stress.

PMID- 22475934
TI  - Allethrin-induced genotoxicity and oxidative stress in Swiss albino mice.
AB  - Allethrin (C(19)H(26)O(3)) is non-cyano-containing pyrethroid insecticide that is
      used extensively for controlling flies and mosquitoes. Apart from its neurotoxic
      effects in non-target species, allethrin is reported to be mutagenic in bacterial
      systems. In this study, we observed oxidative damage-mediated genotoxicity caused
      by allethrin in Swiss albino mice. The genotoxic potential of allethrin was
      evaluated using chromosome aberrations (CAs) and a micronuclei (MN) induction
      assay as genetic end-points. The oral intubation of allethrin (25 and 50mg/kg
      b.wt.) significantly induces CAs and MN in mouse bone marrow cells. The DNA
      damaging potential of allethrin was estimated in mouse liver using the DNA
      alkaline unwinding assay (DAUA) and by measuring the levels of 8-hydroxy-2'-deoxy
      guanosine (8-OH-dG). Furthermore, a dose-dependent increase in reactive oxygen
      species (ROS) generation and lipid peroxidation (LPO), with a concurrent decrease
      in superoxide dismutase (SOD) and catalase, confirm its pro-oxidant potential.
      The DNA-damaging potential of allethrin was found to be mediated through the
      modulation of p53, p21, GADD45alpha and MDM-2. These results confirm the
      genotoxic and the pro-oxidant potential of allethrin in Swiss albino mice.

PMID- 22475935
TI  - Cisplatin treatment leads to changes in nuclear protein and microRNA expression.
AB  - Using a proteomic approach, we have previously shown that exposure to different
      concentrations of cisplatin during a 12-h period can lead to changes in nuclear
      protein expression and alternative splicing in HeLa cells. To further shed light
      on the DNA damage response (DDR) induced by cisplatin, we examined the nuclear
      proteome profiles of HeLa cells treated with 5MUM cisplatin for different times
      (2, 12, and 24h). Two-dimensional electrophoresis (2-DE) identified 98
      differentially expressed proteins in cisplatin-treated cells as compared to
      control cells. Among them, 54 spots (55%) were down-regulated and 44 spots (45%)
      were up-regulated. 51 spots were subjected to Matrix-assisted-laser-desorption
      ionization Time-of-flight/time-of-flight Mass spectrometry (MALDI-TOF/TOF MS)
      identification, and 40 spots were identified. Among these, 22 proteins were
      located in nucleus. These proteins were involved in stress response, cell cycle
      and division, apoptosis, mRNA processing, transport, splicing and microRNA
      (miRNA) maturation. The changed expression of Annexin A1 and Lamin B1 were
      confirmed by Western blot. The role of Annexin A1 in the response to cisplatin
      induced DNA damage was further analyzed, and it was shown that after Annexin A1
      knockdown, cisplatin-induced DNA damage was significantly increased. In addition,
      the changed expression of several miRNAs was also observed by quantitative real
      time PCR (qRT-PCR). Taken together, these data indicate that cisplatin-induced
      DDR is a complex process, and that those proteins identified by proteomics can
      lead to new directions for a better understanding of this process.

PMID- 22475936
TI  - Lactic acid bacteria from fermented table olives.
AB  - Table olives are one of the main fermented vegetables in the world. Olives can be
      processed as treated or natural. Both have to be fermented but treated green
      olives have to undergo an alkaline treatment before they are placed in brine to
      start their fermentation. It has been generally established that lactic acid
      bacteria (LAB) are responsible for the fermentation of treated olives. However,
      LAB and yeasts compete for the fermentation of natural olives. Yeasts play a
      minor role in some cases, contributing to the flavour and aroma of table olives
      and in LAB development. The main microbial genus isolated in table olives is
      Lactobacillus. Other genera of LAB have also been isolated but to a lesser
      extent. Lactobacillus plantarum and Lactobacillus pentosus are the predominant
      species in most fermentations. Factors influencing the correct development of
      fermentation and LAB, such as pH, temperature, the amount of NaCl, the polyphenol
      content or the availability of nutrients are also reviewed. Finally, current
      research topics on LAB from table olives are reviewed, such as using starters,
      methods of detection and identification of LAB, their production of bacteriocins,
      and the possibility of using table olives as probiotics.

PMID- 22475937
TI  - Bacteriophages BCP1-1 and BCP8-2 require divalent cations for efficient control
      of Bacillus cereus in fermented foods.
AB  - Bacillus cereus is a foodborne bacterial pathogen that causes diarrhea and
      vomiting. In this study, the usefulness of bacteriophages to eradicate B. cereus
      from fermented foods was investigated. A total of 13 phages were isolated from
      Korean fermented food products, and 2 (BCP1-1 and BCP8-2) were further
      characterized. Transmission electron microscopy (TEM), restriction enzyme
      digestion pattern analysis, and SDS-PAGE of the structural proteins suggest that
      both phages belong to the family Myoviridae, containing approximately 150 kbp
      long genomes. The host ranges of both phages were limited to B. cereus group
      species (12/13), as they were not able to lyse other Gram-positive or negative
      strains including Bacillus subtilis. Purified phages were used to inhibit B.
      cereus growth in a model fermented food system, cheonggukjang, a fast-fermented
      soybean paste product. BCP1-1 and BCP8-2 were able to effectively eradicate B.
      cereus from the food only if divalent cations (Ca2+, Mg2+, or Mn2+) were added to
      the medium. Further studies reveal that divalent cations are essential for phage
      adsorption, while a monovalent cation (Na+) is required for the post-adsorption
      phase of phage infection. Taken together, our findings imply that a phage could
      be an ideal anti-bacterial agent for use in fermented food products that require
      the presence of beneficial microflora and, during phage application, optimization
      of phage reaction conditions is critical for the successful utilization of phage
      biocontrol.

PMID- 22475938
TI  - Characterization of Fusarium verticillioides strains isolated from maize in
      Italy: fumonisin production, pathogenicity and genetic variability.
AB  - Fusarium verticillioides (teleomorph Gibberella moniliformis) is the main fungal
      agent of ear and kernel rot of maize (Zea mays L.) worldwide, including Italy.
      F.verticillioides is a highly toxigenic species since it is able to produce the
      carcinogenic mycotoxins fumonisins. In this study, 25 F. verticillioides strains,
      isolated from maize in different regions of Italy were analyzed for their ability
      to produce fumonisins, their pathogenicity and their genetic variability. A
      further referenced strain of G. moniliformis isolated from maize in USA was also
      used as outgroup. The fumonisins B1, B2, and B3 were analyzed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Pathogenicity tests were
      carried out by symptom observation and determination of growth parameters after
      inoculation of maize seeds, seedlings and wounded detached leaves. Total genomic
      DNA was used for Amplified Fragment Length Polymorphism (AFLP) analysis. About
      20% of the analyzed strains were unable to produce fumonisins in in vitro
      experiments on inoculated maize flour, while, among fumonisin producers, a great
      variability was observed, with values ranging from 1 to 115 mg kg-1. The
      different analyzed strains showed a wide range of pathogenicity in terms of
      effect on seed germination, seedling development and of symptoms produced on
      detached leaves, which were not correlated with the different in vitro fumonisin
      production. AFLP analysis indicated the presence of genetic diversity not only
      between the Italian strains and the American reference but also among the Italian
      isolates.

PMID- 22475939
TI  - Nitrogen requirements of commercial wine yeast strains during fermentation of a
      synthetic grape must.
AB  - Nitrogen deficiencies in grape musts are one of the main causes of stuck or
      sluggish wine fermentations. Currently, the most common method for dealing with
      nitrogen-deficient fermentations is adding supplementary nitrogen (usually
      ammonium phosphate). However, it is important to know the specific nitrogen
      requirement of each strain, to avoid excessive addition that can lead to
      microbial instability and ethyl carbamate accumulation. In this study, we aimed
      to determine the effect of increasing nitrogen concentrations of three different
      nitrogen sources on growth and fermentation performance in four industrial wine
      yeast strains. This task was carried out using statistical modeling techniques.
      The strains PDM and RVA showed higher growth-rate and maximum population size and
      consumed nitrogen much more quickly than strains ARM and TTA. Likewise, the
      strains PDM and RVA were also the greatest nitrogen demanders. Thus, we can
      conclude that these differences in nitrogen demand positively correlated with
      higher growth rate and higher nitrogen uptake rate. The most direct effect of
      employing an adequate nitrogen concentration is the increase in biomass, which
      involves a higher fermentation rate. However, the impact of nitrogen on
      fermentation rate is not exclusively due to the increase in biomass because the
      strain TTA, which showed the worst growth behavior, had the best fermentation
      activity. Some strains may adapt a strategy whereby fewer cells with higher
      metabolic activity are produced. Regarding the nitrogen source used, all the
      strains showed the better and worse fermentation performance with arginine and
      ammonium, respectively.

PMID- 22475940
TI  - Novel Streptococcus infantarius subsp. infantarius variants harboring lactose
      metabolism genes homologous to Streptococcus thermophilus.
AB  - Streptococcus infantarius subsp. infantarius belongs to the Streptococcus
      bovis/Streptococcus equinus complex (SBSEC) commonly associated with human and
      animal infections. We elucidated the lactose metabolism of S. infantarius subsp.
      infantarius predominant in African fermented milk products. S. infantarius subsp.
      infantarius isolates (n = 192) were identified in 88% of spontaneously fermented
      camel milk suusac samples (n = 24) from Kenya and Somalia at log10 8.2-8.5 CFU mL
      1. African S. infantarius isolates excreted stoichiometric amounts of galactose
      when grown on lactose, exhibiting a metabolism similar to Streptococcus
      thermophilus and distinct from their type strain. African S. infantarius subsp.
      infantarius CJ18 harbors a regular gal operon with 99.7-100% sequence identity to
      S. infantarius subsp. infantarius ATCC BAA-102(T) and a gal-lac operon with 91.7
      97.6% sequence identity to S. thermophilus, absent in all sequenced SBSEC strains
      analyzed. The expression and functionality of lacZ was demonstrated in a beta
      galactosidase assay. The gal-lac operon was identified in 100% of investigated S.
      infantarius isolates (n = 46) from suusac samples and confirmed in Malian
      fermented cow milk isolates. The African S. infantarius variant potentially
      evolved through horizontal gene transfer of an S. thermophilus-homologous lactose
      pathway. Safety assessments are needed to identify any putative health risks of
      this novel S. infantarius variant.

PMID- 22475941
TI  - Effects of nisin, EDTA and salts of organic acids on Listeria monocytogenes,
      Salmonella and native microflora on fresh vacuum packaged shrimps stored at 4 
      degrees C.
AB  - Nisin (500 IU ml-1), EDTA (0.02 M), potassium sorbate (PS) (3%, w/v), sodium
      benzoate (SB) (3%, w/v) or sodium diacetate (SD) (3%, w/v); alone or in
      combination were used to dip uninoculated shrimps and shrimps inoculated with
      Listeria monocytogenes or Salmonella (~4.0-5.0 log CFU g-1). Shrimps were then
      drip-dried, vacuum packaged and stored at 4  degrees C for 7 days. Untreated
      shrimps were used as a control. Numbers of L. monocytogenes, Salmonella and
      native background microflora were determined on uninoculated and inoculated
      shrimps on days 0, 3 and 7. Nisin-EDTA-PS and nisin-EDTA-SD significantly reduced
      (p < 0.05) L. monocytogenes numbers by 1.07-1.27 and 1.32-1.36 log CFU g-1,
      respectively, on day 0 and 3. However, all treatments failed to significantly
      reduce (p > 0.05) Salmonella counts on shrimps throughout storage. On day 7,
      numbers of aerobic bacteria, psychrotrophic bacteria and Pseudomonas on combined
      nisin-EDTA-salt of organic acids treated shrimps were significantly lower (p <
      0.05) by 4.40-4.60, 3.50-4.01, and 3.84-3.99 log CFU g-1 respectively, as
      compared to the control. Dipping in organic acids solutions followed by vacuum
      packaging and chilled storage can help reduce L. monocytogenes and native
      microflora, but not Salmonella, on fresh shrimps.

PMID- 22475942
TI  - Reductions of Vibrio parahaemolyticus in Pacific oysters (Crassostrea gigas) by
      depuration at various temperatures.
AB  - Consumption of raw oysters has been linked to several outbreaks of Vibrio
      parahaemolyticus infection in the United States. This study investigated effects
      of ice storage and UV-sterilized seawater depuration at various temperatures on
      reducing V. parahaemolyticus in oysters. Raw Pacific oysters (Crassostrea gigas)
      were inoculated with a mixed culture of five clinical strains of V.
      parahaemolyticus (10290, 10292, 10293, BE 98-2029 and 027-1c1) at levels of 104-6
      MPN/g. Inoculated oysters were either stored in ice or depurated in recirculating
      artificial seawater at 2, 3, 7, 10, 12.5, and 15  degrees C for 4-6 days. Holding
      oysters in ice or depuration of oysters in recirculating seawater at 2 or 3 
      degrees C for 4 days did not result in significant reductions (P > 0.05) of V.
      parahaemolyticus in the oysters. However, depuration at temperatures between 7
      and 15  degrees C reduced V. parahaemolyticus populations in oysters by >3.0 log
      MPN/g after 5 days with no loss of oysters. Depuration at refrigerated
      temperatures (7-15  degrees C) can be applied as a post-harvest treatment for
      reducing V. parahaemolyticus in Pacific oysters.

PMID- 22475943
TI  - Survival of Lactobacillus rhamnosus strains inoculated in cheese matrix during
      simulated human digestion.
AB  - Survival of probiotic bacteria during transit through the gastrointestinal (GI)
      tract is influenced by a number of environmental variables including stomach
      acidity, bile salts, digestive enzymes and food matrix. This study assessed
      survival of seven selected Lactobacillus rhamnosus strains delivered within a
      model cheese system to the human upper GI tract using a dynamic gastric model
      (DGM). Good survival rates for all tested strains were recorded during both
      simulated gastric and duodenal digestion. Strains H12, H25 and N24 demonstrated
      higher survival capacities during gastric digestion than L. rhamnosus GG strain
      used as control, with H12 and N24 continuing to grow during duodenal digestion.
      Strains L. rhamnosus F17, N24 and R61 showed adhesion properties to both HT-29
      and Caco-2 cells. The ability to attach to the cheese matrix during digestion was
      confirmed by scanning electron microscopy, also indicating production of
      extracellular polysaccharides as a response to acid stress.

PMID- 22475944
TI  - Antimicrobial efficacy of pepsin-digested bovine lactoferrin on spoilage bacteria
      contaminating traditional Mozzarella cheese.
AB  - The aim of this work was to check the efficacy of bovine lactoferrin (BLF) and
      its pepsin-digested hydrolysate (LFH) to control spoilage bacteria contaminating
      the governing liquid of high moisture (HM) Mozzarella cheese during cold storage.
      These natural substances resulted effective when tested in vitro against five
      potential spoilage bacteria contaminating cold-stored HM Mozzarella cheese. Among
      six LFH fractions, only the fraction containing lactoferricins, mainly
      represented by LfcinB17-42, resulted effective against Escherichia coli K12 at
      the same extent of the whole pepsin-digested hydrolysate. LFH tested throughout
      seven days for its antimicrobial activity against the main bacterial groups
      growing in cold-stored commercial HM Mozzarella cheese samples delayed
      significantly the growth of pseudomonads and coliforms in comparison with the un
      treated samples. This is the first report providing a direct evidence of the
      ability of LFH to inhibit the growth of cheese spoilage bacteria.

PMID- 22475945
TI  - Microbiological profile of maize and rye flours, and sourdough used for the
      manufacture of traditional Portuguese bread.
AB  - A thorough microbiological study of maize and rye flours, and sourdoughs obtained
      therefrom for eventual manufacture of broa--a dark sour bread typical in Northern
      Portugal, following artisanal practices, was carried out. Towards this purpose,
      samples were supplied by 14 artisanal producers, selected from 4 sub-regions,
      during two periods of the year. Total viable counts, as well as viable mesophilic
      and thermophilic microorganisms, yeasts and molds, Gram- rods, endospore-forming
      and nonsporing Gram+ rods, and catalase+ and catalase- Gram+ cocci were assayed
      for. The comprehensive experimental dataset unfolded a unique and rather complex
      wild microflora in flours and sourdoughs throughout the whole region, which did
      not discriminate among sub-regions or seasons, or flour source for that matter.
      However, fermentation played a major role upon the numbers of the various
      microbial groups: the viable counts of yeasts, lactobacilli, streptococci,
      lactococci, enterococci and leuconostocs increased, whereas those of molds,
      Enterobacteriaceae, Pseudomonadaceae, staphylococci and micrococci decreased.

PMID- 22475946
TI  - Real-time PCR assays for detection and quantification of aflatoxin-producing
      molds in foods.
AB  - Aflatoxins are among the most toxic mycotoxins. Early detection and
      quantification of aflatoxin-producing species is crucial to improve food safety.
      In the present work, two protocols of real-time PCR (qPCR) based on SYBR Green
      and TaqMan were developed, and their sensitivity and specificity were evaluated.
      Primers and probes were designed from the o-methyltransferase gene (omt-1)
      involved in aflatoxin biosynthesis. Fifty-three mold strains representing
      aflatoxin producers and non-producers of different species, usually reported in
      food products, were used as references. All strains were tested for aflatoxins
      production by high-performance liquid chromatography-mass spectrometry (HPLC-MS).
      The functionality of the proposed qPCR method was demonstrated by the strong
      linear relationship of the standard curves constructed with the omt-1 gene copy
      number and Ct values for the different aflatoxin producers tested. The ability of
      the qPCR protocols to quantify aflatoxin-producing molds was evaluated in
      different artificially inoculated foods. A good linear correlation was obtained
      over the range 4 to 1 log cfu/g per reaction for all qPCR assays in the different
      food matrices (peanuts, spices and dry-fermented sausages). The detection limit
      in all inoculated foods ranged from 1 to 2 log cfu/g for SYBR Green and TaqMan
      assays. No significant effect was observed due to the different equipment,
      operator, and qPCR methodology used in the tests of repeatability and
      reproducibility for different foods. The proposed methods quantified with high
      efficiency the fungal load in foods. These qPCR protocols are proposed for use to
      quantify aflatoxin-producing molds in food products.

PMID- 22475947
TI  - Monitoring of the microbial communities involved in the soy sauce manufacturing
      process by PCR-denaturing gradient gel electrophoresis.
AB  - Soy sauce is a traditional seasoning produced through the fermentation of
      soybeans and wheat using microbes. In this study, the microbial communities
      involved in the soy sauce manufacturing process were analyzed by PCR-Denaturing
      Gradient Gel Electrophoresis (PCR-DGGE). The bacterial DGGE profile indicated
      that the bacterial microbes in the koji were Weissella cibaria (Weissella
      confusa, Weissella kimchii, Weissella salipiscis, Lactobacillus fermentum,
      Lactobacillus plantarum, Lactobacillus iners, or Streptococcus thermophilus),
      Staphylococcus gallinarum (or Staphylococcus xylosus), and Staphylococcus
      kloosii. In addition to these bacteria, Tetragenococcus halophilus was also
      detected in the mash during lactic acid fermentation. The fungal DGGE profile
      indicated that the fungal microbes in the koji were not only Aspergillus oryzae
      but also several yeasts. In the mash, Zygosaccharomyces rouxii appeared in the
      early fermentation stage, Candida etchellsii (or Candida nodaensis) and Candida
      versatilis were detected at the middle fermentation stage, and Candida etchellsii
      was detected at the mature fermentation stage. These results suggest that the
      microbial communities present during the soy sauce manufacturing process change
      drastically throughout its production. This is the first report to reveal the
      microbial communities involved in the soy sauce manufacturing process using a
      culture-independent method.

PMID- 22475948
TI  - Stable and non-competitive association of Saccharomyces cerevisiae, Candida
      milleri and Lactobacillus sanfranciscensis during manufacture of two traditional
      sourdough baked goods.
AB  - The microbiota occurring in all the manufacturing phases of two Italian sourdough
      sweet-leavened baked goods (a typical Genoese dry biscuit, Lagaccio, and a soft
      stuffed North Italian typical cake, Panettone) were investigated over a period of
      three years. The two sourdough mother sponges were characterized by the stable
      presence of three dominant microbial species in potential competition for
      carbohydrates: Lactobacillus sanfranciscensis, Candida milleri, and Saccharomyces
      cerevisiae. Genotypic and phenotypic characterizations of microbial isolates
      pointed out that each mother sponge harbored its own strains, well
      distinguishable by molecular methods of analysis but not differing in their main
      metabolic properties from those known for the corresponding species. The
      microbial and biochemical evolution during the whole production protocol of both
      manufactures demonstrated that the three microbial species grew at almost the
      same growth rates, without exhausting any of the main carbon substrates (maltose,
      glucose and fructose). The quite similar growth dynamics under practical
      conditions and the constant presence of all fermentable carbohydrates were
      recognized as responsible for the stable non competitive association of maltose
      positive and maltose-negative species in both sourdoughs. However, the two
      sourdoughs were characterized by quite different LAB to yeast ratio, with values
      significantly higher in Panettone than in Lagaccio. The cause of this difference
      could mainly be ascribed to the temperature of the mother sponge regeneration
      phase, that, in the case of Panettone manufacture, occurred under conditions of
      moderate refrigeration.

PMID- 22475949
TI  - Novel probiotic candidates for humans isolated from raw fruits and vegetables.
AB  - This study was aimed at determining the probiotic potential of a large number of
      autochthonous lactic acid bacteria isolated from fruit and vegetables. Survival
      under simulated gastric and intestinal conditions showed that 35% of the strains,
      mainly belonging to the species Lactobacillus plantarum maintained high cell
      densities. Selected strains did not affect the immune-mediation by Caco-2 cells.
      All strains stimulated all 27 immune-mediators by peripheral blood mononuclear
      cells (PBMC). A significant (P<0.05; P<0.01) increase of the major part of
      cytokines and growth factors was found. A few chemokines were stimulated. Immune
      mediators with pro-inflammatory activity (IL-17, EOTAXIN and IFNgamma) were
      significantly (P<0.01) stimulated by all strains, followed by IL-1b>IP-10>IL
      6>MIP1alpha. Stimulation of IL-12, IL-2 and IL-7 was strain dependent. Only a few
      strains increased the synthesis of cytokines with anti-inflammatory activity. Six
      L. plantarum strains were further selected. Four were defined as the strongly
      adhesive strains (more than 40 bacteria adhering to one Caco-2 cell), and 2 as
      the adhesive strains (5-40 bacteria adhering to one Caco-2 cell). Five strains
      grew and acidified chemically defined medium with fructo-oligosaccharides (FOS)
      as the only carbon source. End-products of FOS fermentation were found. All
      strains inhibited enterohemorragic Escherichia coli K12 and Bacillus megaterium
      F6 isolated from human sources. The results of this study showed that some
      autochthonous lactic acid bacteria from raw fruit and vegetables have functional
      features to be considered as novel probiotic candidates.

PMID- 22475950
TI  - Differentiation of mixed lactic acid bacteria communities in beverage
      fermentations using targeted terminal restriction fragment length polymorphism.
AB  - Lactic acid bacteria (LAB) are an important group of bacteria in beer and wine
      fermentations both as beneficial organisms and as spoilage agents. However,
      sensitive, rapid, culture-independent methods for identification and community
      analyses of LAB in mixed-culture fermentations are limited. We developed a
      terminal restriction fragment length polymorphism (TRFLP)-based assay for the
      detection and identification of lactic acid bacteria and Bacilli during wine,
      beer, and food fermentations. This technique can sensitively discriminate most
      species of Lactobacillales, and most genera of Bacillales, in mixed culture, as
      indicated by both bioinformatic predictions and empirical observations. This
      method was tested on a range of beer and wine fermentations containing mixed LAB
      communities, demonstrating the efficacy of this technique for discriminating LAB
      in mixed culture.

PMID- 22475951
TI  - Isolation and lytic activity of the Listeria bacteriophage endolysin LysZ5
      against Listeria monocytogenes in soya milk.
AB  - The endolysin gene (lysZ5) from the genome of the Listeria monocytogenes phage
      FWLLm3 was cloned in Escherichia coli and characterized. Comparative sequence
      analysis revealed that lysZ5 resembled the murein hydrolase ply511 encoded by L.
      monocytogenes phage A511. The encoded protein LysZ5 had a predicted molecular
      mass of 35.8 kDa and was expressed in E. coli as an N-terminal fusion protein of
      41.5 kDa. Addition of purified fusion protein to lawns of indicator bacteria
      showed that LysZ5 could lyse L. monocytogenes, Listeria innocua and Listeria
      welshimeri, but not Staphylococcus aureus or Enterococcus faecalis. The purified
      protein was able to kill L. monocytogenes growing in soya milk, with the pathogen
      concentration reduced by more than 4 log10 CFU ml-1 after 3 h incubation at 4 
      degrees C. As far as we know, this is the first report of a Listeria phage
      endolysin to control pathogens in soya milk and to demonstrate endolysin activity
      in foods at refrigeration temperatures. Moreover, LysZ5 may also be useful for
      biocontrol in other ready-to-eat foods.

PMID- 22475952
TI  - Gain control in molecular information processing: lessons from neuroscience.
AB  - Statistical properties of environments experienced by biological signaling
      systems in the real world change, which necessitates adaptive responses to
      achieve high fidelity information transmission. One form of such adaptive
      response is gain control. Here, we argue that a certain simple mechanism of gain
      control, understood well in the context of systems neuroscience, also works for
      molecular signaling. The mechanism allows us to transmit more than 1 bit (on or
      off) of information about the signal independent of the signal variance. It does
      not require additional molecular circuitry beyond that already present in many
      molecular systems, and in particular, it does not depend on existence of feedback
      loops. The mechanism provides a potential explanation for abundance of
      ultrasensitive response curves in biological regulatory networks.

PMID- 22475953
TI  - A brief overview of electroporation pulse strength-duration space: a region where
      additional intracellular effects are expected.
AB  - Electroporation (EP) of outer cell membranes is widely used in research,
      biotechnology and medicine. Now intracellular effects by organelle EP are of
      growing interest, mainly due to nanosecond pulsed electric fields (nsPEF). For
      perspective, here we provide an approximate overview of EP pulse strength
      duration space. This overview locates approximately some known effects and
      applications in strength-duration space, and includes a region where additional
      intracellular EP effects are expected. A feature of intracellular EP is direct,
      electrical redistribution of endogenous biochemicals among cellular compartments.
      For example, intracellular EP may initiate a multistep process for apoptosis. In
      this hypothesis, initial EP pulses release calcium from the endoplasmic
      reticulum, followed by calcium redistribution within the cytoplasm. With further
      EP pulses calcium penetrates mitochondrial membranes and causes changes that
      trigger release of cytochrome c and other death molecules. Apoptosis may
      therefore occur even in the presence of apoptotic inhibitors, using pulses that
      are smaller, but longer, than nsPEF.

PMID- 22475954
TI  - [Hashimoto's encephalopathy].
AB  - Hashimoto's encephalopathy was first described by Lord Brain in 1966. Since,
      other designations have been proposed and the existence of the disease itself has
      been debated. However, the number of reported cases in the literature is still
      increasing and physicians are sometimes confronted with patients with
      neuropsychiatric manifestations and positive thyroid antibodies. This article is
      an update based upon a search through Medline database that identified 316
      references published between 1961 and 2011. Hashimoto's encephalopathy is a rare
      condition for which there is a need for both diagnostic criteria and therapeutic
      consensus.

PMID- 22475955
TI  - [Post-transfusional iron overload, iron loading anemia].

PMID- 22475957
TI  - Increasing complexity of clinical research in gastroenterology: implications for
      the training of clinician-scientists.
AB  - OBJECTIVES: Significant advances have been made in clinical and epidemiologic
      research methods over the past 30 years. We sought to demonstrate the impact of
      these advances on published gastroenterology research from 1980 to 2010. METHODS:
      Twenty original clinical articles were randomly selected from each of three
      journals from 1980, 1990, 2000, and 2010. Each article was assessed for topic,
      whether the outcome was clinical or physiologic, study design, sample size,
      number of authors and centers collaborating, reporting of various statistical
      methods, and external funding. RESULTS: From 1980 to 2010, there was a
      significant increase in analytic studies, clinical outcomes, number of authors
      per article, multicenter collaboration, sample size, and external funding. There
      was increased reporting of P values, confidence intervals, and power
      calculations, and increased use of large multicenter databases, multivariate
      analyses, and bioinformatics. CONCLUSIONS: The complexity of clinical
      gastroenterology and hepatology research has increased dramatically, highlighting
      the need for advanced training of clinical investigators.

PMID- 22475958
TI  - How the FDA manages drug safety with black box warnings, use restrictions, and
      drug removal, with attention to gastrointestinal medications.

PMID- 22475959
TI  - Image of the month: Ectopic ascites.

PMID- 22475962
TI  - Healing erosive esophagitis with a proton pump inhibitor: the more the merrier?
AB  - Patients with erosive esophagitis (EE) account for 30% of patients with
      gastroesophageal reflux disease; only a minority of these patients fail to
      achieve healing on treatment with a proton pump inhibitor (PPI), once-daily, for
      8 weeks. For those patients with EE who have failed to heal on a PPI, given once
      daily, current practice is to double the PPI dose although there is little
      published evidence to support this. In this issue of the American Journal of
      Gastroenterology, authors from Japan have demonstrated that double-dose PPI
      produced higher healing rates when given as a split, twice-daily dose than as a
      once-daily dose for patients with EE who had failed initial therapy with
      rabeprazole 10 mg once-daily. Quadruple-dose PPI, given as a split dose, did not
      increase the healing rates but did produce better symptom control, albeit
      limited, compared with double-dose PPI, given twice-daily. Because subjects,
      initially, received a lower PPI dose than that generally indicated for EE
      (rabeprazole 20 mg daily), this study does not provide the eagerly awaited
      justification for double-dose PPI therapy in patients with EE who have failed
      standard-dose PPI once-daily. However, it does demonstrate the clinical advantage
      of a split-dose regimen (AM and PM), compared with a once-daily regimen, when
      doubling the dose of a PPI for patients with residual EE after initial therapy.

PMID- 22475963
TI  - Imaged-enhanced technologies for colorectal polyp detection and classification.
AB  - An early diagnosis of colorectal polyp can be achieved through screening and
      surveillance programs. In the past few years, advances in endoscopic imaging of
      the colorectal mucosa have been extensively developed, leading to an increased
      detection of pre-malignant lesions as well as low-grade and nonneoplastic polyps.
      In order to reduce the overall cost of care with minimal impact on the quality of
      care in colorectal cancer prevention, the "diagnosis and discard" strategy has
      been considered. High-definition, narrow band imaging and confocal endomicroscopy
      are image enhancement technologies that have been widely studied lately. The
      studies from Pasha et al. and Kuiper et al. demonstrate the limitations of these
      new advanced imaging technologies and that further studies should continue to be
      developed.

PMID- 22475967
TI  - Fluid volume in acute pancreatitis: how much is too much?

PMID- 22475968
TI  - Potential hazards of submucosal injection of methylene blue.

PMID- 22475969
TI  - Weekend effect in non-variceal upper gastrointestinal bleeding: data from nine
      italian gastrointestinal units.

PMID- 22475970
TI  - Commentary on "risk factors for early-onset and late-onset hepatocellular
      carcinoma in Asian immigrants with hepatitis B in the United States".

PMID- 22475975
TI  - Acquired cholesteatoma in children: strategies and medium-term results.
AB  - OBJECTIVES: To assess paediatric cholesteatoma surgical management strategies,
      residual disease and recurrence rates and especially the medium-term auditory
      impact. MATERIAL AND METHODS: Retrospective study of 22 cases of acquired middle
      ear cholesteatoma selected from a series of 77 children under the age of 16
      operated for cholesteatoma between 1st January 2000 and 31st December 2003 on the
      basis of the following criteria: first-line surgical management with
      postoperative follow-up greater than four years. Surgical strategies,
      preoperative and postoperative (at 1 year and at the final visit) audiograms and
      residual disease and recurrence rates were analysed. RESULTS: A canal wall up
      tympanoplasty was performed in 82% of cases as first-line procedure and a canal
      wall down tympanoplasty was performed in 32% of cases. Residual cholesteatoma was
      observed in 9% of cases and recurrent disease was observed in 18% of cases. The
      mean preoperative hearing loss was 26dB with an air-bone gap of 23dB with values
      of 26dB and 20dB respectively at the end of follow-up. CONCLUSION: The majority
      of children were operated by two-stage canal wall up tympanoplasty. Long-term
      hearing results remained stable and close to preoperative values. The recurrence
      rate (residual disease and relapse) was low (27%), as reported in the literature.

PMID- 22475976
TI  - Prognostic impact of tumour multifocality in thyroid papillary microcarcinoma
      based on a series of 160 cases.
AB  - OBJECTIVE: The objective of this study was to evaluate the prognostic impact of
      tumour multifocality in papillary thyroid microcarcinoma (PTMC). METHODS: All
      patients who underwent total thyroidectomy and central neck dissection for PTMC
      in our institution between 1990 and 2007 were included in this retrospective
      study. Statistical correlations between tumour multifocality and various clinical
      or pathological prognostic parameters were assessed by univariate and
      multivariate analyses. RESULTS: A total of 160 patients (133 women and 27 men;
      mean age: 47.8+/-13.7 years) were included in this study. Tumour multifocality
      was demonstrated in 59 (37%) patients. Central neck metastatic lymph node
      involvement was identified in 46 (28%) patients. No statistical correlation was
      demonstrated between tumour multifocality and the following factors: age, gender,
      tumour size, extension beyond the thyroid, metastatic central neck lymph node
      involvement and risk of recurrence. A tumour diameter greater than 5mm was
      associated with a higher risk of recurrence (P=0.008). CONCLUSION: Tumour
      multifocality does not appear to have a prognostic impact in PTMC.

PMID- 22475977
TI  - Localized nasopharyngeal amyloidosis.
AB  - OBJECTIVES: To illustrate, via a case report, how a differential diagnosis of
      amyloidosis is to be suspected in case of a nasopharyngeal mass. CASE REPORT: A
      59-year-old woman presented with bilateral nasal obstruction with associated
      episodic tubal dysfunction. Physical examination found a mass occupying the
      entire nasopharynx, initially suggestive of tumor. DISCUSSION: Amyloidosis was
      diagnosed on histopathologic study of the biopsy and surgical specimens.
      Exploration for systemic disease proved negative. The localized amyloidosis was
      managed conservatively. At 9 months' follow-up, there was no recurrence.
      CONCLUSION: Localized amyloidosis, however rare, should be considered as
      differential diagnosis in any case of nasal obstruction with tubal dysfunction,
      even if bilateral. ENT physicians need to recognize and understand this pathology
      for adapted diagnostic and treatment planning.

PMID- 22475978
TI  - A cervical cyst which was not one at all.

PMID- 22475979
TI  - The free thoracodorsal artery perforator flap in head and neck reconstruction.

PMID- 22475980
TI  - Facial nerve identification during parotidectomy.

PMID- 22475981
TI  - A retrosynthetic biology approach to therapeutics: from conception to delivery.
AB  - De novo biosynthetic pathways are designed, assembled and optimized to produce
      high-value compounds such as drugs and chemical building blocks from renewable
      resources. Microorganisms are used as synthetic platforms of systems biology
      where biochemical pathways are engineered into the host metabolic network.
      Retrosynthetic biology offers a creative pathway design concept that has gained
      interest because of its potential to identify novel metabolic ways for
      therapeutic production. Retrosynthetic biology uses the backward search of
      retrosynthetic analysis to devise and optimize tailor-made pathways. The
      retrosynthetic process can be seamlessly integrated into a complete circuitry
      system for therapeutic applications where production, sensing and delivery act as
      constitutive interconnecting parts. The aim of this review is to highlight recent
      efforts toward synthetic design for therapeutic development.

PMID- 22475982
TI  - The diagnostic value of water immersion skin wrinkling and Neuropads in small
      fiber neuropathy.
AB  - OBJECTIVE: To investigate the diagnostic yield of two simple tests for small
      fiber neuropathy (SFN): Neuropads(r) and water immersion skin wrinkling (WISW).
      METHODS: We studied 35 patients clinically diagnosed with SFN and 61 age- and sex
      matched healthy controls. Wrinkling was judged as absent (abnormal), or present
      (normal) after immersion of the hands for 30 min. Neuropads are plasters
      impregnated with cobalt blue that are applied with to the soles of the feet.
      These remain blue when feet are dry (abnormal) or turn pink when there is some
      moisture (normal). RESULTS: The sensitivity of the Neuropad was 29% and its
      specificity 93%. The sensitivity of WISW was 66% and its specificity 70%.
      Regarding abnormality of at least one test to define the combination as abnormal
      yielded a sensitivity of 71% and specificity 67%. When both tests had to be
      abnormal to judge the combination abnormal, sensitivity was 23% and specificity
      97%. CONCLUSIONS: The Neuropad has a high specificity, so an abnormal result can
      be used to confirm SFN. WISW has a moderate sensitivity and specificity.
      Combining these two tests can be helpful: when both tests are abnormal the
      diagnosis SFN is highly likely. SIGNIFICANCE: The Neuropad and WISW can be
      helpful in daily practice by supporting the diagnosis SFN.

PMID- 22475983
TI  - Fluorescence imaging of potassium ions in living cells using a fluorescent probe
      based on a thrombin binding aptamer-peptide conjugate.
AB  - When a biotinylated FRET probe based on a peptide-thrombin binding aptamer
      conjugate was introduced together with streptavidin and biotinylated nuclear
      export signal peptide into HeLa cells, the resulting ternary complex enabled
      visualization of K(+) concentration changes in the cell.

PMID- 22475984
TI  - Characteristics of high-risk sexual behaviors for human immunodeficiency virus
      infection among Iranian drug abusers.
AB  - OBJECTIVES: This study was conducted to estimate the prevalence and the
      associated factors of high-risk sexual behaviors among drug abusers referred to a
      methadone clinic in Gorgan, the capital of Golestan province in the northeast of
      Iran, to help health care decision makers on designing interventional programs.
      METHODS: In this cross-sectional study, 400 drug abusers referred to our
      methadone clinic were evaluated for high-risk sexual behavior. A logistic
      regression model was fitted for the association between independent variables and
      high-risk sexual behavior. RESULTS: Approximately a quarter of patients (25.5%)
      had high-risk sexual behavior among which 47% had not used a condom in their last
      sexual contact. Drug abusers who had poor economic status had a lower chance of
      high-risk sexual behavior than those with good economic status (adjusted odds
      ratio [AOR] = 0.35, 95% confidence interval [CI] = 0.13-0.96). Also, 1-year
      increase in age reduced the chance by 6% (AOR = 0.94, 95% CI = 0.91-0.98). Heroin
      abusers, compared with opium abusers, had a duplicated chance of having high-risk
      sex (AOR = 2.11, 95% CI = 1.12-3.96). CONCLUSION: According to this study, high
      risk sexual behavior in the drug abusers referred to methadone clinic was
      associated with younger age, good economic status, and heroin addiction. Hence,
      in interventional planning, more attention should be paid to young drug abusers,
      patients with good economic status, and heroin addicts as well.

PMID- 22475985
TI  - Comparisons of analgesic potency and side effects of buprenorphine and
      buprenorphine with ultra-low-dose naloxone.
AB  - OBJECTIVES: Opioids are the most effective pain medication available, yet
      concerns about their safety may limit their administration to those in need. In
      efforts to identify analgesics with lower potential for abuse and dependence,
      recent evidence suggests that combinations of opioids with ultra-low doses of the
      opioid antagonist naloxone may enhance the analgesic effect with increased
      safety. This study investigated the use of buprenorphine (0.3 mg) plus ultra-low
      dose naloxone (0.02 mg) (BUP + ULDN) as compared with buprenorphine alone (0.3
      mg) (BUP) for the treatment of pain. METHODS: In a double-blind, placebo
      controlled, randomized cross-over design, 12 study participants with lingering,
      noncancer pain received each medication intravenously for 5 days of dosing,
      separated by an intertrial interval of at least 7 days to avoid possible
      carryover effects. RESULTS: We found no order effects and no differences between
      medications in pre- to postdose pain ratings, side effects, or adverse events.
      CONCLUSIONS: These findings suggest that BUP + ULDN is not more effective in
      reducing pain than BUP.

PMID- 22475986
TI  - Optimization of the preparation of GaN-based specimens with low-energy ion
      milling for (S)TEM.
AB  - We report on optimization of electron transparent GaN based specimens for
      transmission electron microscopy (TEM) and scanning TEM (STEM) studies by
      combining focused ion beam thinning and low-energy (<=500 eV) Ar-ion milling.
      Energy dependent ion milling effects on GaN based structures are investigated and
      the quality of ion milled samples is compared with that of specimens prepared by
      wet chemical etching. Defects formed during ion milling lead to amorphization of
      the specimen. The experimental results are compared with Monte-Carlo simulations
      using the SRIM (stopping and range of ions in matter) software. Specimen
      thickness was deduced from high-angle annular dark field STEM images by
      normalization of measured intensities with respect to the intensity of the
      scanning electron probe and comparison with multislice simulations in the frozen
      lattice approach. The results show that the thickness of the amorphous surface
      layer can be successfully reduced below 1 nm by low energy ion milling, leading
      to a homogeneous image contrast in TEM and STEM, so that good conditions for
      quantitative analysis can be achieved. For an ion energy of 400 eV the thickness
      measurements resulted in an etching rate of about 6-8 nm/min.

PMID- 22475987
TI  - Single-molecule dynamics of transcription of the lar promoter.
AB  - We measured the in vivo production of RNA molecules tagged with MS2d-GFP in
      Escherichia coli, driven by the lar promoter, under weak and medium induction.
      The distributions of intervals between consecutive productions of RNAs are found
      to be sub-exponential, and the process of RNA production is found to be sub
      Poissonian. We discuss possible models of transcription initiation and, based on
      our results and previous in vitro measurements, find that a sequential two-step
      model of transcription initiation at the promoter region explains the results
      well.

PMID- 22475988
TI  - Age-related changes in gene expression in tissues of the sea urchin
      Strongylocentrotus purpuratus.
AB  - The life history of sea urchins is fundamentally different from that of
      traditional models of aging and therefore they provide the opportunity to gain
      new insight into this complex process. Sea urchins grow indeterminately,
      reproduce throughout their life span and some species exhibit negligible
      senescence. Using a microarray and qRT-PCR, age-related changes in gene
      expression were examined in three tissues (muscle, esophagus and nerve) of the
      sea urchin species Strongylocentrotus purpuratus. The results indicate age
      related changes in gene expression involving many key cellular functions such as
      the ubiquitin-proteasome pathway, DNA metabolism, signaling pathways and
      apoptosis. Although there are tissue-specific differences in the gene expression
      profiles, there are some characteristics that are shared between tissues
      providing insight into potential mechanisms that promote lack of senescence in
      these animals. As an example, there is an increase in expression of genes
      encoding components of the Notch signaling pathway with age in all three tissues
      and a decrease in expression of the Wnt1 gene in both muscle and nerve. The
      interplay between the Notch and Wnt pathways may be one mechanism that ensures
      continued regeneration of tissues with advancing age contributing to the general
      lack of age-related decline in these animals.

PMID- 22475989
TI  - Fe3O4@mesoporous SBA-15: a robust and magnetically recoverable catalyst for one
      pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones via the Biginelli reaction.
AB  - A magnetic nanoparticle conjugated mesoporous nanocatalyst (Fe(3)O(4)@mesoporous
      SBA-15) with a high surface area has been synthesized by chemical conjugation of
      magnetite (Fe(3)O(4)) nanoparticles with functionalized mesoporous SBA-15.
      Functionalized mesoporous SBA-15 containing surface carboxyl and amino groups was
      synthesized via the thiol-ene click reaction of cysteine hydrochloride and vinyl
      functionalized SBA-15. The catalytic activity of the robust, safe and
      magnetically recoverable Fe(3)O(4)@mesoporous SBA-15 nanocatalyst was evaluated
      in the Biginelli reaction under mild conditions for the synthesis of a diverse
      range of 3,4-dihydropyrimidin-2(1H)-ones. The separation and reuse of the
      Fe(3)O(4)@mesoporous SBA-15 nanocatalyst were simple, effective and economical.

PMID- 22475990
TI  - Terminal investment and senescence in rhesus macaques (Macaca mulatta) on Cayo
      Santiago.
AB  - Long-lived iteroparous species often show aging-related changes in reproduction
      that may be explained by 2 non-mutually exclusive hypotheses. The terminal
      investment hypothesis predicts increased female reproductive effort toward the
      end of the life span, as individuals have little to gain by reserving effort for
      the future. The senescence hypothesis predicts decreased female reproductive
      output toward the end of the life span due to an age-related decline in body
      condition. Nonhuman primates are ideal organisms for testing these hypotheses, as
      they are long lived and produce altricial offspring heavily dependent on maternal
      investment. In this study, we integrated 50 years of continuous demographic
      records for the Cayo Santiago rhesus macaque (Macaca mulatta) population with new
      morphometric and behavioral data to test the senescence and terminal investment
      hypotheses. We examined relationships between maternal age and activity, mother
      and infant body condition, interbirth intervals, measures of behavioral
      investment in offspring, and offspring survival and fitness to test for age
      associated declines in reproduction that would indicate senescence, and for age
      associated increases in maternal effort that would indicate terminal investment.
      Compared with younger mothers, older mothers had lower body mass indices and were
      less active, had longer interbirth intervals, and spent more time in contact with
      infants, but had infants of lower masses and survival rates. Taken together, our
      results provide strong evidence for the occurrence of reproductive senescence in
      free-ranging female rhesus macaques but are also consistent with some of the
      predictions of the terminal investment hypothesis.

PMID- 22475991
TI  - Grandparenting today is changing gerontological nursing practice.

PMID- 22475994
TI  - Sleep apnea-plus: prevalence, risk factors, and association with cardiovascular
      diseases using United States population-level data.
AB  - OBJECTIVES: The purpose of this study was to estimate the prevalence of, to
      identify sociodemographic risk factors for, and to examine the association of
      cardiovascular diseases with sleep apnea-plus (i.e., comorbid insomnia and sleep
      apnea) in the general United States population. METHODS: A population-based multi
      year cross-sectional study design was used with data from the 2005-2008 United
      States National Health and Nutrition Examination Surveys (NHANES) (n=12,593).
      RESULTS: The prevalence of insomnia among individuals with sleep apnea (n=236/546
      or 43%) was higher compared to individuals without sleep apnea (n=3550/12,047 or
      30%). Among individuals with sleep apnea, women (OR 2.19, 95% CI 1.07-4.48) and
      individuals with symptoms of depression (OR 3.53, 95% CI 1.49-8.35) were
      significantly more likely, and individuals ages 60+ years (OR 0.43, 95% CI 0.20
      0.94) and individuals with morbid obesity (OR 0.27, 95% CI 0.09-0.75) were
      significantly less likely, to have sleep apnea-plus. After controlling for
      confounders, the odds of health professional-diagnosed self-reported hypertension
      (OR 0.64, 95% CI 0.29-1.44), diabetes (OR 1.02, 95% CI 0.33-3.11), congestive
      heart failure (OR 0.67, 95% CI 0.19-2.44), myocardial infarction (OR 1.80, 95% CI
      0.49-6.67), and stroke (OR 0.82, 95% CI 0.18-3.77), as well as objectively
      measured risk factors for these conditions, were not significantly different
      between individuals with sleep apnea-plus and individuals with sleep apnea-alone.
      CONCLUSIONS: The prevalence of insomnia in sleep apnea is high, and substantially
      greater than in the general population, and this has important implications for
      the management of sleep apnea patients. Similar to sleep apnea-alone, individuals
      with sleep apnea-plus have elevated rates of cardiovascular diseases compared to
      the general population. Given the elevated rates of cardiovascular diseases among
      individuals with sleep apnea-plus, along with their known poor CPAP compliance,
      identification of individuals with sleep apnea-plus and treatment of their
      concomitant insomnia is important.

PMID- 22475995
TI  - Measures of forest fire smoke exposure and their associations with respiratory
      health outcomes.
AB  - PURPOSE OF REVIEW: Exposure to forest fire smoke is episodic, which makes its
      health effects challenging to study. We review the newest contributions to a
      growing literature on acute respiratory outcomes. RECENT FINDINGS: Smoke exposure
      was associated with increases in self-reported symptoms, medication use,
      outpatient physician visits, emergency room visits, hospital admissions, and
      mortality. The associations were strongest for the outcomes most specific to
      asthma. SUMMARY: Studies with varied approaches to exposure assessment and varied
      measures of respiratory outcomes were consistent among themselves, and consistent
      with most previous work.

PMID- 22475996
TI  - Bronchial thermoplasty for severe asthma.
AB  - PURPOSE OF REVIEW: Bronchial thermoplasty, which involves the delivery of radio
      frequency energy to the airways to reduce airway smooth muscle mass, has been
      recently introduced for the treatment of severe asthma. This review summarizes
      the preclinical development, efficacy and adverse effects of bronchial
      thermoplasty. In addition, the potential mechanisms of action and place in
      management of severe asthma are discussed. RECENT FINDINGS: The efficacy and
      adverse profile of bronchial thermoplasty has been assessed in three randomized
      controlled trials, the first two of which showed clinical benefits of bronchial
      thermoplasty compared with usual care in patients with moderate or severe asthma.
      The third trial reports the results of a comparison with sham bronchial
      thermoplasty in 288 adults with severe asthma. Bronchial thermoplasty improved
      asthma quality of life questionnaire scores compared with sham bronchial
      thermoplasty; in the posttreatment period, there were fewer severe exacerbations
      and emergency department visits. Bronchial thermoplasty causes short-term
      increases in asthma-related morbidity. Follow-up data to date support the long
      term safety of the procedure. SUMMARY: Bronchial thermoplasty has a role in the
      management of patients with severe asthma who have uncontrolled symptoms despite
      current therapies. Future studies need to identify factors that predict a
      beneficial clinical response.

PMID- 22475997
TI  - Telemanagement in asthma:  an innovative and effective approach.
AB  - PURPOSE OF REVIEW: Information and communication technology (ICT) could
      potentially help to reduce the considerable burden of asthma that still exists
      despite wide availability of effective therapies. Telemanagement is an
      interactive and proactive management approach consisting of an ongoing
      partnership of patients and professionals supported by ICT and focused on
      clinical outcomes and patient goals in the individual. This review highlights
      recent developments in telemanagement in the ongoing management of patients with
      asthma focused on the effectiveness, cost-effectiveness and implementation of
      telemanagement in asthma care. RECENT FINDINGS: An increasing number of studies
      address the effectiveness of components or a comprehensive telemanagement
      intervention in children and adults with mild to severe asthma. Telemanagement of
      asthma in the individual patient includes key components of asthma management,
      such as education, self-monitoring, goal setting, written action plans and
      regular medical review. Such a comprehensive telemanagement approach is effective
      in improving quality of life and clinical outcomes, especially in adult patients
      with moderate to severe asthma. CONCLUSION: Telemanagement of asthma can be an
      effective and cost-effective approach tailored to the individual patient needs.
      More research is needed on the long-term effectiveness and cost-effectiveness of
      telemanagement of patients with asthma under real-world conditions and on
      effective implementation strategies.

PMID- 22475998
TI  - Vitamin D and atopy and asthma phenotypes in children.
AB  - PURPOSE OF REVIEW: To give an overview of the recent research into whether a lack
      of vitamin D contributes to the development of atopy and asthma in childhood.
      RECENT FINDINGS: I describe here the recent epidemiological studies relating
      vitamin D status to atopy and asthma in children, focusing on determinants of
      major asthma phenotypes in childhood. Recent findings include the observations
      that vitamin D levels are inversely associated with degree of corticosteroid use,
      worsening airflow limitation and increased exacerbations among asthmatics. Low
      vitamin D has been associated with atopy and asthma in children and adolescents
      in a community cohort, predominantly in boys, with vitamin D at age 6 predicting
      these outcomes at 14. I also detail the mechanistic studies examining relevant
      vitamin D-regulated processes; recent findings include the demonstration that
      offspring of mice with vitamin D deficiency in pregnancy show reduced lung volume
      and function. SUMMARY: The current literature suggests that intervention to
      ensure adequate vitamin D levels during both pregnancy and childhood may reduce
      the development of atopy and asthma in children. However, important questions
      need to be answered regarding the levels of vitamin D required, which may vary
      between the sexes and between individuals, and the optimal timing and duration of
      such intervention.

PMID- 22476000
TI  - A Mn36Ni4 'loop-of-loops-and-supertetrahedra' aggregate possessing a high S(T) =
      26 +/- 1 spin ground state.
AB  - The initial use of 1,3-propanediol in mixed Mn/3d cluster chemistry has led to a
      Mn(III)(28)Mn(II)(8)Ni(II)(4) molecular aggregate which consists of two
      Mn(III)(8)Ni(2) loops and two Mn(III)(6)Mn(II)(4) supertetrahedral units and
      displays a high ground spin state value S(T) = 26 +/- 1.

PMID- 22475999
TI  - Nonallergen-specific treatments for food allergy.
AB  - PURPOSE OF REVIEW: This review summarizes recent reports on nonallergen-specific
      therapies for food allergy. These therapies are especially appealing for food
      allergy because unlike allergen-specific immunotherapy, they would allow the
      treatment of multiple food allergies in a single patient with one therapy. RECENT
      FINDINGS: Chinese herbal therapy, anti-IgE, probiotics, engineered lactic acid
      bacteria, and helminth therapy are all examples of allergen nonspecific therapies
      that have been investigated in recent years. Although some have only been studied
      in animal models of food allergy, some are undergoing rigorous, human clinical
      trials. SUMMARY: Increasing amounts of research are examining the efficacy and
      safety of nonallergen-specific therapies for food allergy. There is hope that
      clinicians will have effective treatments either as an alternative or as an
      adjunct to immunotherapy.

PMID- 22476001
TI  - Cardiovascular effects of treatment with taxanes.
AB  - Taxanes are cytotoxic drugs that stabilize cellular microtubules and are among
      the most active of the antineoplastic agents being widely used in the treatment
      of cancer patients. Furthermore, taxanes comprise a valuable tool in
      interventional cardiology. Following treatment with taxanes, in many patients,
      the risk of cardiovascular complications has recently been noted. This review
      examines the cardiac toxicity of treatment with taxanes and their use in
      cardiology and analyzes issues in clinical practice.

PMID- 22476002
TI  - Feasibility and safety of transradial approach and bivalirudin treatment in
      elderly patients undergoing early invasive strategy for ACS:  'The OLDER Research
      Project' preliminary study.

PMID- 22476003
TI  - Hierarchical self-organization of cytoskeletal active networks.
AB  - The structural reorganization of the actin cytoskeleton is facilitated through
      the action of motor proteins that crosslink the actin filaments and transport
      them relative to each other. Here, we present a combined experimental
      computational study that probes the dynamic evolution of mixtures of actin
      filaments and clusters of myosin motors. While on small spatial and temporal
      scales the system behaves in a very noisy manner, on larger scales it evolves
      into several well distinct patterns such as bundles, asters and networks. These
      patterns are characterized by junctions with high connectivity, whose formation
      is possible due to the organization of the motors in 'oligoclusters'
      (intermediate-size aggregates). The simulations reveal that the self-organization
      process proceeds through a series of hierarchical steps, starting from local
      microscopic moves and ranging up to the macroscopic large scales where the steady
      state structures are formed. Our results shed light on the mechanisms involved in
      processes such as cytokinesis and cellular contractility, where myosin motors
      organized in clusters operate cooperatively to induce the structural organization
      of cytoskeletal networks.

PMID- 22476004
TI  - Neural basis of the potentiated inhibition of repeated haloperidol and clozapine
      treatment on the phencyclidine-induced hyperlocomotion.
AB  - Clinical observations suggest that antipsychotic effect starts early and
      increases progressively over time. This time course of antipsychotic effect can
      be captured in a rat phencyclidine (PCP)-induced hyperlocomotion model, as
      repeated antipsychotic treatment progressively increases its inhibition of the
      repeated PCP-induced hyperlocomotion. Although the neural basis of acute
      antipsychotic action has been studied extensively, the system that mediates the
      potentiated effect of repeated antipsychotic treatment has not been elucidated.
      In the present study, we investigated the neuroanatomical basis of the
      potentiated action of haloperidol (HAL) and clozapine (CLZ) treatment in the
      repeated PCP-induced hyperlocomotion. Once daily for five consecutive days, adult
      Sprague-Dawley male rats were first injected with HAL (0.05 mg/kg, sc), CLZ (10.0
      mg/kg, sc) or saline, followed by an injection of PCP (3.2 mg/kg, sc) or saline
      30 min later, and motor activity was measured for 90 min after the PCP injection.
      C-Fos immunoreactivity was assessed either after the acute (day 1) or repeated
      (day 5) drug tests. Behaviorally, repeated HAL or CLZ treatment progressively
      increased the inhibition of PCP-induced hyperlocomotion throughout the five days
      of drug testing. Neuroanatomically, both acute and repeated treatment of HAL
      significantly increased PCP-induced c-Fos expression in the nucleus accumbens
      shell (NAs) and the ventral tegmental area (VTA), but reduced it in the central
      amygdaloid nucleus (CeA). Acute and repeated CLZ treatment significantly
      increased PCP-induced c-Fos expression in the ventral part of lateral septal
      nucleus (LSv) and VTA, but reduced it in the medial prefrontal cortex (mPFC).
      More importantly, the effects of HAL and CLZ in these brain areas underwent a
      time-dependent reduction from day 1 to day 5. These findings suggest that
      repeated HAL achieves its potentiated inhibition of the PCP-induced
      hyperlocomotion by acting on the NAs, CeA and VTA, while CLZ does so by acting on
      the mPFC, LSv and VTA.

PMID- 22476005
TI  - Report: Combustion Byproducts and Their Health Effects: Summary of the 10th
      International Congress.
AB  - The 10th International Congress on Combustion Byproducts and their Health Effects
      was held in Ischia, Italy, from June 17-20, 2007. It is sponsored by the US
      NIEHS, NSF, Coalition for Responsible Waste Incineration (CRWI), and Electric
      Power Research Institute (EPRI). The congress focused on: the origin,
      characterization, and health impacts of combustion-generated fine and ultrafine
      particles; emissions of mercury and dioxins, and the development/application of
      novel analytical/diagnostic tools. The consensus of the discussion was that
      particle-associated organics, metals, and persistent free radicals (PFRs)
      produced by combustion sources are the likely source of the observed health
      impacts of airborne PM rather than simple physical irritation of the particles.
      Ultrafine particle-induced oxidative stress is a likely progenitor of the
      observed health impacts, but important biological and chemical details and
      possible catalytic cycles remain unresolved. Other key conclusions were: (1) In
      urban settings, 70% of airborne fine particles are a result of combustion
      emissions and 50% are due to primary emissions from combustion sources, (2) In
      addition to soot, combustion produces one, possibly two, classes of nanoparticles
      with mean diameters of ~10 nm and ~1 nm. (3) The most common metrics used to
      describe particle toxicity, viz. surface area, sulfate concentration, total
      carbon, and organic carbon, cannot fully explain observed health impacts, (4)
      Metals contained in combustion-generated ultrafine and fine particles mediate
      formation of toxic air pollutants such as PCDD/F and PFRs. (5) The combination of
      metal-containing nanoparticles, organic carbon compounds, and PFRs can lead to a
      cycle generating oxidative stress in exposed organisms.

PMID- 22476006
TI  - Impairment of sensory-motor plasticity in mild Alzheimer's disease.
AB  - BACKGROUND: Primary motor cortex (M1) is relatively spared in the early stages of
      Alzheimer's disease (AD). OBJECTIVE: Aim of the present study was to investigate
      whether abnormal M1 synaptic plasticity is present at an early stage of AD. We
      employed an electrophysiological protocol, named rapid paired associative
      stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS)
      paired with electrical stimulation of the contralateral median nerve, that
      modifies corticospinal excitability and short latency afferent inhibition (SAI).
      METHODS: We studied 10 patients with a diagnosis of probable mild AD according to
      the Mini Mental State Examination score (minimum 21) and 14 age-matched control
      subjects. Motor evoked potentials (MEP) amplitudes and short-afferent inhibition
      (SAI) were measured at baseline before and for up to 60 min after 5Hz-rPAS in
      abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial
      magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median
      nerve stimulation preceding TMS over the contralateral M1 at an inter-stimulus
      interval of 25 ms. RESULTS: Baseline SAI was significantly reduced in AD
      patients. In the control subjects rPAS induced a significant increase in MEP
      amplitudes and a decrease of SAI in the APB muscle persistently for up to 1 h.
      Conversely 5Hz-rPAS did not induce any significant changes in MEP amplitudes and
      SAI in mild AD patients. CONCLUSIONS: Sensory-motor plasticity is impaired in the
      motor cortex of AD at an early stage of the disease.

PMID- 22476007
TI  - Macrodystrophia lipomatosa.
AB  - OBJECTIVE: We present a series of six cases of macrodystrophia lipomatosa (MDL)
      and their outcome after debulking surgery. MATERIAL AND METHODS: The study was
      conducted from 2002 to 2005; the cases are selected from outpatients department
      of postgraduate institute of medical education and research. The patients were in
      the age group of 2-5 years of age with the complaints of progressive increase in
      size of the toe, difficulty in walking and recurrent injury to the foot. RESULTS:
      There were no complication in three (50%) cases but two cases (33%) had skin
      blackening along the suture margins, One case (16%) was under corrected. And none
      of the cases had recurrence. CONCLUSION: Simple debulking surgery is sufficient
      for MDL.

PMID- 22476008
TI  - Efficacy of antimicrobials for the disinfection of pathogen contaminated green
      bell pepper and of consumer cleaning methods for the decontamination of knives.
AB  - While there is strong focus on eliminating pathogens from produce at a commercial
      level, consumers can employ simple methods to achieve additional pathogen
      reductions in the domestic kitchen. To determine the ability of antimicrobials to
      decontaminate peppers, samples of green bell pepper were inoculated with
      Salmonella enterica and Escherichia coli O157:H7 and then immersed in 3% (v/v)
      hydrogen peroxide (H2O2), 2.5% (v/v) acetic acid (AA), 70% (v/v) ethyl alcohol
      (EtOH), or sterile distilled water (SDW). The potential for transfer of pathogens
      from contaminated peppers to other non-contaminated produce items, and the effect
      of knife disinfection in preventing this cross contamination, were also tested.
      Knife disinfection procedures were evaluated by chopping inoculated peppers into
      1 cm2 pieces with kitchen knives. Experimental knives were then treated by either
      no treatment (control), wiping with a dry sterile cotton towel, rinsing under
      running warm water for 5 or 10s, or applying a 1% (v/v) lauryl sulfate-based
      detergent solution followed by rinsing with warm running water for 10s. Following
      disinfection treatment, knives were used to slice cucumbers. Exposure to H2O2 for
      5 min and EtOH for 1 min resulted in reductions of 1.3+/-0.3 log10 CFU/cm2 for
      both pathogens. A 5 min exposure to AA resulted in a reduction of S. enterica of
      1.0+/-0.7 log10 CFU/cm2 and E. coli of 0.7+/-0.8 log10 CFU/cm2. No differences (p
      >= 0.05) were found between numbers of pathogens on knives and numbers of
      pathogens transferred to cucumber slices, suggesting that organisms remaining on
      knife surfaces were transferred to cucumbers during slicing. Findings suggest
      that EtOH and H2O2 may be effective antimicrobials for in-home decontamination of
      peppers, and that use of detergent and warm water is effective for
      decontamination of implements used during meal preparation.

PMID- 22476009
TI  - Changes in posterior airway space, pulmonary function and sleep quality,
      following bimaxillary orthognathic surgery.
AB  - Bimaxillary orthognathic surgery (BOS) is commonly used in the correction of
      severe Class III deformities (mandibular prognathism with maxillary
      retrognathism). The postural response of the pharyngeal airway after mandibular
      setback and maxillary advancement procedures is clinically crucial for
      maintaining optimum respiration. Patients might suffer from obstructive sleep
      apnoea, postoperatively. The aim of this study was to determine the effects of
      BOS on pharyngeal airway space, respiratory function during sleep and pulmonary
      functions. 21 male patients were analysed using cephalometry, spirometry for
      pulmonary function tests, and a 1 night sleep study for full polysomnography
      before and 17+/-5 months after BOS. The data show that the hyoid bone
      repositioned to the inferior, the tongue and soft palate displaced to the
      posterior, narrowed at the oropharynx and hypopharynx and widened at the
      nasopharynx and velopharynx levels significantly (p<0.05). The alterations
      indicated decreased airway resistance and better airflow. As a consequence of
      polysomnography evaluation, the sleep quality and efficiency of the patients
      improved significantly after BOS. Patients who undergo BOS should be monitored
      with pulmonary function tests and polysomnography pre- and postoperatively to
      detect any airway obstruction.

PMID- 22476010
TI  - A study of emotion work in student paramedic practice.
AB  - Student paramedics are exposed to the harsh reality of paramedic practice early
      within preregistration education (British Paramedic Association (BPA) 2006).
      Active involvement in the emergency assessment, management and treatment of
      potentially life threatening and traumatic incidents involves exposure to human
      suffering, pain, trauma and death. Managing their own and others' emotions would
      appear to be integral. There is however, a paucity of research evidencing the
      emotional aspects of paramedic practice and none which specifically captures the
      student perspective. A qualitative, exploratory design and semi-structured
      interviews were undertaken with eight second year undergraduate paramedic science
      students to explore their perceptions and experiences of emotion work and the
      strategies used to deal with it. Thematic content analysis revealed three main
      themes, 'getting on with the job', 'struggling with emotion' and 'talking it
      through'. This paper presents the findings on the first two themes. Emergency
      resuscitation and getting on with the job emerged as a priority in a number of
      the experiences and subthemes included control and suppression of emotion, 'got
      to deal with it' and 'don't see them as a person'. Students struggled to deal
      with patients' and relatives' emotions and their own in some situations and
      subthemes included 'not sure of what to say', 'stop myself crying', and 'personal
      links'. The findings provide evidence of the emotional demands of student
      paramedic practice and have important implications for the curriculum content
      which must prepare and support students to perform emotion work effectively.

PMID- 22476011
TI  - Role of peripheral and spinal 5-HT2B receptors in formalin-induced nociception.
AB  - In this study we assessed the role of local peripheral and spinal serotonin 2B (5
      HT(2B)) receptors in rats submitted to the formalin test. For this, local
      peripheral ipsilateral, but not contralateral, administration of the highly
      selective 5-HT(2B) receptor antagonist 2-amino-4-(4-fluoronaphth-1-yl)-6
      isopropylpyridine (RS-127445, 0.01-1 nmol/paw) significantly prevented 1%
      formalin-induced flinching behavior. Moreover, local peripheral ipsilateral, but
      not contralateral, of the selective 5-HT(2) receptor agonist (+/-)-2,5-dimethoxy
      4-iodoamphetamine hydrochloride (DOI, 1-10 nmol/paw) augmented 0.5% formalin
      induced nociceptive behavior. The local pronociceptive effect of the 5-HT(2)
      receptor agonist DOI (10 nmol/paw) was significantly prevented by the local
      injection of RS-127445 (0.01 nmol/paw). Moreover, intrathecal injection of the
      selective 5-HT(2B) receptor antagonist RS-127445 (0.1-10 nmol/rat) also prevented
      1% formalin-induced nociceptive behavior. In contrast, spinal injection of the 5
      HT(2) receptor agonist DOI (1-10 nmol/rat) significantly increased flinching
      behavior induced by 0.5% formalin. The spinal pronociceptive effect of the 5
      HT(2) receptor agonist DOI (10 nmol/rat) was prevented by the intrathecal
      injection of the 5-HT(2B) receptor antagonist RS-127445 (0.1 nmol/rat). Our
      results suggest that the 5-HT(2B) receptors play a pronociceptive role in
      peripheral as well as spinal sites in the rat formalin test. 5-HT(2B) receptors
      could be a target to develop analgesic drugs.

PMID- 22476012
TI  - Alterations on the morphology, nitric oxide synthesis and activity of platelets
      reproduced in rats as possible biomarkers for depression are reversed by
      fluoxetine.
AB  - Biochemical markers associated with the prognosis of depression in humans are
      being described in the literature, whereas experimental studies in animal models
      in search for antidepressant strategies are lacking. The aim of this study was to
      evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis
      as possible biomarkers of depressive-like behavior by using FST alone and in the
      presence of fluoxetine. Naive rats were compared to those receiving vehicle or
      fluoxetine at 10mg/kg i.p. in acute, subchronic and chronic administration in the
      FST. After behavioral assessment, platelets were isolated from blood samples and
      analyzed by flow cytometry to determine the platelet mitochondrial membrane
      potential and NO synthesis. In addition, HPLC and electron microscopy were used
      to examine 5-HT and tryptophan levels and morphology of platelets, respectively.
      Rats receiving vehicle and exposed to FST showed depressive-like behavior at all
      the times tested; after chronic FST rats showed a similar pattern of alteration
      in platelet morphology and in the studied as possible biochemical markers as
      those previously recognized in depressive humans. Depressive-like behavior in
      rats exposed to FST was prevented in the presence of fluoxetine administration at
      all the times tested and associated with the prevention of alterations in
      platelet morphology, platelet activity and NO synthesis, and/or in 5-HT
      concentrations. The results of the present study suggest that platelet function
      and morphology might be relevant markers for the prognosis of depression and the
      search for functional treatments. Besides, the relevance of FST as model to study
      this psychiatric illness is reinforced.

PMID- 22476013
TI  - Effect of time period after boric acid injection on 10B absorption in different
      regions of adult male rat's brain.
AB  - Distribution of (10)B in different regions of rat normal brain was studied. Two
      groups were chosen as control and trial. Trial group received 2 ml of neutral
      boron compound. 2, 4 and 6 h after the injection brain removed, coronal sections
      of forebrain, midbrain and hindbrain were sandwiched between two pieces of
      polycarbonate. Autoradiography plots of (10)B distribution showed significant
      differences in three regions with the highest (10)B concentration in the
      forebrain during 4 h after injection.

PMID- 22476014
TI  - Correction for radon distribution in solid/liquid and air phases in gamma-ray
      spectrometry.
AB  - The effect of radon diffusion and distribution between a (226)Ra matrix and the
      top air gap inside sample containers for gamma-ray spectrometry was studied.
      Containers filled at almost 100% or just 70% of total capacity yielded correction
      factors of about 7% and 20% respectively. Applying these correction factors
      allowed activity values calculated from (226)Ra or radon decay products to agree
      within 2%.

PMID- 22476015
TI  - High beam current operation of a PETtraceTM cyclotron for 18F- production.
AB  - Upgrades and optimisation achieved 160 MUA total target current operation of a GE
      PETtrace cyclotron in dual target mode for the routine production of [(18)F]FDG
      for >2 years. Approximately 900 GBq of (18)F(-) and >500 GBq of [(18)F]FDG can be
      produced routinely in a single production run, meeting the routine [(18)F]FDG
      requirements with our customer base and achieving economies of scale. Production
      of >1 TBq of (18)F(-) in a single run was achieved. Reliability, saturation and
      synthesis yields were not adversely affected.

PMID- 22476016
TI  - Activity standardisation of 45Ca and 204Tl using the new TDCR system at CMI.
AB  - A new triple-to-double coincidence ratio (TDCR) system has been established at
      CMI as an additional technique for primary activity standardisation. Details of
      the detectors and the electronics are given. Construction of the optical chamber
      was validated using measurement of a (3)H standard-the efficiency achieved with
      Ultima Gold was 58%. Several methods of efficiency variation (coloured bands
      painted on vial, positioning and photomultipliers defocussing) are compared.
      Activity concentrations of (204)Tl and (45)Ca were determined with the TDCR
      method and with the efficiency tracer technique. Advantages of the TDCR method
      compared to the efficiency tracing method and agreement between results are
      shown.

PMID- 22476017
TI  - Performance evaluation of commercial radionuclide calibrators in Indonesian
      hospitals.
AB  - Dose calibrator is one of the supporting equipments in the field of nuclear
      medicine. At the hospitals, dose calibrator is used for activity measurement of
      radiopharmaceutical before it is administered to patients. Comparison of activity
      measurements of (131)I and (99m)Tc with dose calibrators was organized in
      Indonesia during 2007-2010 with the the aim of obtaining information dose
      calibrator performance in the hospitals. Seven Indonesian hospitals participated
      in this comparison. The measurement results were evaluated using the E(n)
      criteria. The result presented in this paper facilitated the evaluation of dose
      calibrator performance at several hospitals.

PMID- 22476018
TI  - Comparison of thermoluminescence (TL) and cathodoluminescence (ESEM-CL)
      properties between hydrothermal and metamorphic quartzes.
AB  - This paper reports on the Thermoluminescence (TL) and Cathodoluminescence (CL)
      emission of well-characterized hydrothermal milky quartz specimens from Hakkari
      in Turkey, labeled THQ, and Madrid in Spain, labeled SHQ, and metamorphic quartz
      from Madrid, in Spain, labeled SMQ. Both hydrothermal and metamorphic quartz
      samples display similar UV-IR CL spectra consisting of five groups of components
      centered at 330 nm and 380 nm linked to [AlO(4)] degrees  centers, 420 nm due to
      intrinsic defects such as oxygen vacancies, lattice defects, and impurities which
      modify the crystal structure, 480 nm associated with [AlO(4)] degrees  centers of
      substitutional Al(3+), and a red broad band related to the hydroxyl defects in
      the quartz lattice as precursors of non-bridging oxygen hole centers (NBOHC) and
      substitutional point defects. The Turkish quartz specimen exhibits higher CL
      intensity in the UV region (up to 330 nm) than the Spanish specimens probably
      linked to the presence of Ca (0.95% in THQ and less than 0.1% in SHQ and SMQ). At
      wavelengths greater than 330 nm, SMQ (formed at high pressure 6000 bars and
      temperatures over 500-600 degrees C) shows higher intensity than the hydrothermal
      (growth at 2000 bars and temperatures 200-300 degrees C) samples associated with
      the formation process. The natural blue TL glow curves of both THQ and SHQ
      display a weaker TL intensity than the SMQ, attributable to the Al (0.32%), Ti
      (0.14%), K (0.01%) and Zr (76 ppm) content. It is shown that mineralogical
      formation, crystallinity index and the content of the impurities seem to be the
      main parameters of influence in the shape intensity of the CL and TL glow curve
      emission.

PMID- 22476019
TI  - Determination of plutonium content in high burnup pressurized water reactor fuel
      samples and its use for isotope correlations for isotopic composition of
      plutonium.
AB  - The content of plutonium isotopes in high burnup pressurized water reactor fuel
      samples was examined using both alpha spectrometry and mass spectrometry after
      anion exchange separation. The measured values were compared with results
      calculated by the ORIGEN-2 code. On average, the ratios (m/c) of the measured
      values (m) over the calculated values (c) were 1.22+/-0.16 for (238)Pu, 1.02+/
      0.14 for (239)Pu, 1.08+/-0.06 for (240)Pu, 1.06+/-0.16 for (241)Pu, and 1.13+/
      0.08 for (242)Pu. Using the Pu data obtained in this work, correlations were
      derived between the alpha activity ratios of (238)Pu/((239)Pu+(240)Pu), the alpha
      specific activities of Pu, and the atom % abundances of the Pu isotopes. Using
      these correlations, the atom % abundances of the plutonium isotopes in the target
      samples were calculated. These calculated results agreed within a range from 2 to
      8% of the experimentally derived values according to the isotopes of plutonium.

PMID- 22476020
TI  - Abortion associated with Chlamydia abortus in extensively reared Iberian sows.
AB  - Reproductive disease was investigated in Iberian pigs on an extensive farrow-to
      finish farm in the southwest of Spain. Chlamydia abortus was isolated in cell
      culture and C. abortus-specific PCR products were detected in placental and fetal
      tissues. In one batch of 14 sows, the percentage of sera positive for C. abortus
      specific antibodies increased from 35.7% to 85.7% in the period of 2 weeks
      following abortion. C. abortus may play a role in abortion in extensively reared
      Iberian sows.

PMID- 22476021
TI  - Multimodality imaging of the mitral paravalvular abscess cavity with left
      ventriculo-atrial fistula.
AB  - Paravalvular complications may occur in patients with infective endocarditis.
      Paravalvular abscess formation rarely occurs and if so it generally involves the
      aortic valve. Herein we present a case of left ventriculo-atrial fistula
      formation through mitral paravalvular abscess cavity shown by multimodality
      imaging including two- and real-time three-dimensional transoesophageal
      echocardiography (RT 3-D TEE), cardiac magnetic resonance imaging (CMRI),
      multislice computed tomography (MSCT) and ventriculography in a patient with a
      mechanical prosthetic mitral valve. This is the first case in the literature of a
      mechanical prosthetic mitral valve complicated by a left ventriculo-atrial
      fistula formation in a healed abscess cavity that is demonstrated with RT-3D TEE,
      cardiac MRI and MSCT.

PMID- 22476022
TI  - A suggested paradigm for coronary risk screening in asymptomatic persons-
      assessment of total coronary atheromatous burden.
AB  - Coronary risk factors are poor at predicting adverse cardiac events in the
      individual patient, with more than 75% of all hard coronary events occurring in
      persons classified as low or intermediate risk. Myocardial ischaemia testing of
      asymptomatic persons is an inappropriate measure of myocardial infarction risk,
      and is plagued by a preponderance of false positive and false negative tests.
      Total coronary atheromatous burden as measured by non-invasive CT coronary
      calcium scoring, may provide the best contemporary measure of coronary risk, and
      offer a rational cost-effective approach to long-term management.

PMID- 22476023
TI  - Aldosterone-to-renin ratio as a predictor of stroke under conditions of high
      sodium intake: the Ohasama study.
AB  - BACKGROUND: Aldosterone is thought to have deleterious effects on the
      cardiovascular system. The aldosterone-to-renin ratio (ARR) is more reproducible
      than aldosterone levels alone and could be an index for inappropriate aldosterone
      secretion or activity. We previously reported the apparent relation between ARR
      and hypertension in subjects with high sodium intake. This prospective study
      investigated the risk of ARR for a first stroke in a general population
      stratified by sodium intake. METHODS: We obtained plasma renin activity (PRA) and
      plasma aldosterone concentrations (PAC) for 883 participants aged >= 35 years not
      receiving antihypertensive treatment in the general population of Ohasama (mean
      age: 59.0 +/- 11.3 years; 65.6% women). RESULTS: Over a mean of 10.9 follow-up
      years, 45 strokes occurred. The median PRA, PAC, and ARR were 1.2 ng/ml/h, 6.4
      ng/dl, and 5.3 ng/dl per ng/ml/h, respectively. Using Cox regression, we computed
      hazard ratios adjusted for sex, age, body mass index (BMI), and systolic blood
      pressure. No association between logARR and stroke was observed in subjects
      overall. However, in subjects with high sodium intake (>= median of 4,058 mg/day
      (salt equivalent, 10.5 g/day)), each 1 s.d. increase in logARR was associated
      with an increased hazard ratio for stroke (hazard ratio: 1.49, P = 0.04). No
      significant association was observed in subjects with low sodium intake (P =
      0.7). When we repeated all the analyses using logPRA or logPAC, no significant
      associations were found. CONCLUSION: These results suggest that high ARR, that
      is, relative aldosterone excess, is a predictor for stroke under conditions of
      high sodium intake.

PMID- 22476025
TI  - Prokaryotic transport in electrohydrodynamic structures.
AB  - When a high-voltage direct-current is applied to two beakers filled with water, a
      horizontal electrohydrodynamic (EHD) bridge forms between the two beakers. In
      this work we study the transport and behavior of bacterial cells added to an EHD
      bridge set-up. Organisms were added to one or to both beakers, and the transport
      of the cells through the bridge was monitored using optical and microbiological
      techniques. It is shown that Escherichia coli top10 (Invitrogen, Carlsbad, CA,
      USA) and bioluminescent E. coli YMC10 with a plasmid (pJE202) containing Vibrio
      fischeri genes can survive the exposure to an EHD liquid bridge set-up and the
      cells are drawn toward the anode due to their negative surface charge.
      Dielectrophoresis and hydrostatic forces are likely to be the cause for their
      transport in the opposite direction which was observed as well, but to a much
      lesser extent. Most E. coli YMC10 bacteria which passed the EHD bridge exhibited
      increased luminescent activity after 24 h. This can be explained by two likely
      mechanisms: nutrient limitation in the heavier inoculated vials and a 'survival
      of the strongest' mechanism.

PMID- 22476024
TI  - Periodontal disease and incidence of hypertension in the health professionals
      follow-up study.
AB  - BACKGROUND: Recent studies suggest a possible association between periodontal
      disease and hypertension; however, prospective evidence is limited. METHODS: The
      study population consisted of 31,543 participants of the Health Professionals'
      Follow-Up Study (HPFS) prospective cohort who were 40-75 years old at baseline,
      had no prior hypertension history and had complete baseline information on oral
      health. Information on periodontal disease, hypertension and potential
      confounders was updated biennially. We used Cox proportional hazards models to
      study the relation between periodontal disease at baseline, during follow-up,
      periodontal bone loss severity, baseline number of teeth, and tooth loss during
      follow-up, and the risk of developing hypertension. Multivariate models included
      age, calendar time, race, comprehensive smoking index (CSI), diabetes, alcohol
      consumption, family history of hypertension, dental profession, body mass index
      (BMI), physical activity, fruit and vegetable intake, multivitamin use, calcium,
      vitamin D and vitamin E intake. RESULTS: We identified 10,828 cases of incident
      hypertension over 20 years of follow-up. After adjusting for potential
      confounders, we did not observe significant associations between incident
      hypertension and periodontal disease at baseline (relative risk (RR) = 1.04; 95%
      confidence interval (CI): 0.98-1.10), periodontitis during follow-up (RR = 1.01;
      95% CI: 0.96-1.05), tooth loss during follow-up (RR = 1.03; 95% CI: 0.98-1.09),
      or when comparing men with 0-10 teeth to men with >= 25 teeth at baseline (RR =
      1.05; 95% CI: 0.91-1.21). Participants reporting severe periodontal bone loss had
      a RR for incident hypertension of 1.02 compared to those without bone loss (95%
      CI: 0.77-1.35). CONCLUSIONS: We did not observe an association between
      periodontal disease measures and incident hypertension in this cohort of middle
      aged men.

PMID- 22476026
TI  - Ultrafast molecular rotor: an efficient sensor for premelting of natural DNA.
AB  - Structural changes in nucleic acids in the premelting region (T < melting
      temperature, T(m)) play an important role in the biological activity of DNA at
      physiological temperature. In the present communication we report the use of an
      ultrafast molecular rotor as an extrinsic fluorescence sensor to monitor the
      structural changes in natural DNA at T < T(m), which could not be detected even
      by circular dichroism spectroscopy. Further, the fluorescence sensor used in the
      present study is superior than most commonly used DNA stains.

PMID- 22476027
TI  - Two three-dimensional {V16Ge4}-based open frameworks stabilized by diverse types
      of Co(II)-amine bridges and magnetic properties.
AB  - Two novel three-dimensional (3D) extended vanadogermanate-based frameworks,
      [Co(pdn)(2)](3)[Co(2)(pdn)(4)][V(16)Ge(4)O(44)(OH)(2)(H(2)O)].5H(2)O (1),
      [Co(2)(en)(3)][Co(en)(2)](2)[Co(en)(2)(H(2)O)][V(16)Ge(4)O(44)(OH)(2)(H(2)O)].10.
      H(2)O (2), (pdn = 1,2-propanediamine, en = ethylenediamine) have been synthesized
      under hydrothermal conditions via changing the organic amine. X-ray crystal
      structure analyses reveal that both frameworks are built of
      [V(16)Ge(4)O(44)(OH)(2)(H(2)O)](10-) anions and different Co-amine cations. They
      represent the first example of incorporating elemental Co into the extended
      vanadogermanate frameworks. Compound 1 shows a 3D framework with NaCl topology
      based on {V(16)Ge(4)} clusters as nodes, while compound 2 exhibits a 3D (4,6)
      connected network with a Schlafli symbol of (4(6).6(7).8(2))(2)(4(2).6(4)), which
      is found for the first time in polyoxovanadate chemistry. The diverse types of
      metal-organoamine subunits play critical roles in the formation on the final
      structures. Furthermore, variable temperature susceptibility measurements on
      compounds 1 and 2 demonstrate the presence of anticipated rare ferrimagnetic
      behavior.

PMID- 22476028
TI  - MicroRNAs and myocardial infarction.
AB  - PURPOSE OF REVIEW: We will review the role of microRNAs (miRNAs), small noncoding
      RNAs with regulatory function, in myocardial infarction (MI). Specifically, we
      will examine the effect of MI on miRNAs' expression in the heart, the effect of
      MI on circulating miRNAs, which miRNAs' overexpression or downmodulation appears
      to have a therapeutic role in MI and which cardiac miRNAs are modulated by
      drugs/experimental molecules/cell transplantation strategies which have an
      established or potential therapeutic role in MI. RECENT FINDINGS: A rapidly
      increasing number of studies are showing that cardiac and circulating miRNAs are
      markedly altered in MI. These novel findings shed new light on the mechanisms
      that lead to MI complications, post-MI ventricular remodeling and cardiac repair.
      Further, recent studies show that circulating miRNAs may represent novel and
      sensitive biomarkers of MI and, possibly, also an intercellular signaling
      mechanism. Overexpression and downregulation of specific miRNAs are being
      evaluated as a novel approach to the treatment of MI. Finally, it appears that
      some established and potential MI therapies (approved drugs/experimental
      molecules/cell therapy interventions) may act, at least in part, via modulation
      of specific miRNAs. SUMMARY: Although miRNAs' role in MI is still largely
      uncharacterized, recent studies suggest that miRNAs may represent novel
      therapeutic targets and MI biomarkers.

PMID- 22476029
TI  - Genome-wide studies of gene expression relevant to coronary artery disease.
AB  - PURPOSE OF REVIEW: Genome-wide association studies have led to the discovery of
      many single nucleotide polymorphisms (SNPs) associated with coronary artery
      disease (CAD). However, many of these SNPs are in between genes (intergenic), and
      presumably function through the regulation of gene expression. Microarrays that
      measure the expression of thousands of mRNAs have allowed investigators to study
      how genetic variation alters gene expression at a genome-wide level. Combining
      these methods has led to progress in understanding the molecular basis for the
      genetic susceptibility to atherosclerosis. RECENT FINDINGS: Recent studies
      confirm that gene expression differences due to genetic variation play an
      underlying role in atherosclerosis. Expression levels of SORT1 are negatively
      correlated with an intergenic risk allele on chromosome 1p13.3 that was
      previously associated with CAD. Increased SORT1 expression leads to lower hepatic
      secretion of low-density lipoprotein (LDL), providing a mechanistic link between
      a common risk variant and disease. In addition, three out of 13 newly identified
      CAD risk loci were found to strongly affect the expression of nearby genes.
      Another recent study detected variants adjacent to a newly identified
      atherosclerosis risk locus on chromosome 11q22 that were associated with the
      expression of platelet-derived growth factor D (PDGFD). SUMMARY: Cataloging the
      genetics of gene expression provides a small but crucial molecular link between
      genetics and clinical phenotypes such as atherosclerosis. Thus, gene expression
      is an endophenotype that can lead to the discovery of the underlying genes
      responsible for increasing atherosclerosis risk and potential diagnostic and
      therapeutic targets.

PMID- 22476030
TI  - GATA2 is expressed at critical times in the mouse uterus during pregnancy.
AB  - In mammals, such as mouse and human, timely production of the progesterone
      receptor (PR) in the proper uterine compartments is critical for preparing the
      uterus for the initiation and maintenance of pregnancy. Developmentally, the
      expression of GATA2, a member of the six member zinc-finger family of
      transcription factors, has been shown to be necessary for multiple non-related
      tissues, such as the hematopoietic system, adipose maturation and the urogential
      system. We recently identified Gata2 as a potential progesterone target gene in
      the mouse uterus; however, the expression of the GATA genes in the mouse uterus
      during pregnancy has not been demonstrated. In the present study, we examined the
      expression of GATA2 protein during the phases of pregnancy, including early
      pregnancy where progesterone (P4) signaling is critical in order to facilitate
      the window of receptivity for embryo implantation and during the decidualization
      of the uterine stroma, a process of cellular proliferation and differentiation
      which is necessary for maintenance of the invading embryo until placentation
      occurs. Here, we report that GATA2 protein is expressed in the uterine luminal
      and glandular epithelium pre-implantation, spatio-temporally co-localizing with
      that of the PR. Additionally, GATA2 continues to be expressed in the decidualized
      stroma throughout early pregnancy indicating a role in the maintenance of
      decidual cells. Based on these findings, we conclude that GATA2 is expressed
      during critical phases of early pregnancy, similar to that of the PR, and that it
      may play a major role in mediating P4 signaling in the mouse uterus.

PMID- 22476031
TI  - Spatial autocorrelation: an overlooked concept in behavioral ecology.

PMID- 22476032
TI  - Cortisol in hair, body mass index and stress-related measures.
AB  - Hair cortisol concentrations (HCC) are assumed to reflect integrated cortisol
      secretion over extended periods of time and may provide a sensitive marker for
      stress-associated endocrine changes. Here, we report data from two independent
      studies of 155 (study I) and 58 participants (study II) in which HCC associations
      with different stress-related measures and body mass index (BMI) were
      investigated. Consistent evidence for positive associations between HCC and BMI
      was seen across both studies (study I: r=.33, p<.001; study II: r=.42, p=.001).
      On the other hand, findings failed to reveal reliable HCC associations with
      psychosocial variables, showing only a positive relationship with self-reported
      social overload in study II (r=.29, p=.03) but not with other stress-related
      measures.

PMID- 22476033
TI  - Autonomic and cortical reactivity in acute and chronic posttraumatic stress.
AB  - This study investigated attention (P300 amplitude) and orienting (skin
      conductance amplitude) to auditory tones in a standard oddball task in early
      trauma-exposed groups (Acute Stress Disorder: ASD) (n=12) or no ASD (n=13),
      compared to individuals with chronic posttraumatic stress disorder (PTSD) (n=17)
      and non-trauma-exposed controls (n=17). Individuals with ASD displayed
      significantly higher SCR and P3 amplitudes to target tones than individuals with
      PTSD, non-traumatized controls, and traumatized controls. These findings suggest
      that attention and orienting responses are greater to neutral, task-relevant
      target tones in ASD than PTSD and traumatized and non-traumatized controls.

PMID- 22476034
TI  - Imaging tumours of the penis.
AB  - Malignant primary epithelial tumours of the penis are rare and mainly affect
      uncircumcised men in their fifties to seventies. They are most frequently located
      in the glans and foreskin. Imaging is performed if the clinician has doubts about
      deep extension, after a diagnostic biopsy. High-resolution ultrasound and above
      all MRI are used to detect invasion of the corpora cavernosa and spongiosum. The
      lesion is often seen as a moderate T2 hyposignal, making it possible to
      distinguish it from the relative hypersignal of the corpora cavernosa. The
      sentinel lymph nodes are inguinal. Adenopathy is frequently present, but does
      not, however, necessarily reflect tumour invasion, as secondary infection of the
      lesion, which is often ulcerated, is common. The prognosis for T1 N0 tumours is
      good, at the cost of mutilating ablation. Extension to the lymph nodes is
      detrimental. Non-epithelial tumours and metastases are even rarer.

PMID- 22476035
TI  - How to characterise a solid renal mass: a new classification proposal for a
      simplified approach.
AB  - The reference method for characterising a solid renal mass is computed
      tomography. MRI and ultrasound can provide useful diagnostic information for
      characterising masses the cystic or solid nature of which it is not possible to
      determine from data from the CT scan. For characterising a solid mass, only MRI
      can replace the CT scan in most cases. Once a mass has been shown to be solid and
      vascularised and not occurring in a context suggesting an inflammatory
      pseudotumour, it can be put, using CT, into one of the four categories of the
      classification that we propose: pseudotumoral dysmorphisms (type 1); typical high
      fat angiomyolipomas (type 2); suspect indeterminate tumours (type 3); typically
      malignant tumours (type 4).

PMID- 22476036
TI  - Four allantoinase genes are expressed in nitrogen-fixing soybean.
AB  - Soybean (Glycine max L. [Merr]) plants export nitrogen from the nodules as
      ureides during symbiotic biological nitrogen fixation. Ureides also play a role
      as nitrogen storage compounds in the seeds and are broken down in germinating
      seedlings. In this work we identified four soybean genes encoding allantoinase
      (E.C. 3.5.2.5), an enzyme involved in both ureide production in nodules and
      ureide catabolism in leaves and other sink tissues. We examined ureide content,
      allantoinase enzyme activity and expression of these genes, which we term GmALN1
      through GmALN4, in germinating seedlings and in vegetative tissues from 45 day
      old soybean plants. GmALN1 and GmALN2 transcripts were measured in all tissues,
      but similar levels of expression of GmALN3 and GmALN4 was only observed in
      nodules. The soybean allantoinase genes seem to have arisen through tandem gene
      duplication followed by a whole genome duplication. We looked for evidence of the
      tandem duplication in common bean (Phaseolus vulgaris L.) and present evidence
      that it occured sometime in the bean lineage before these two species diverged,
      but before soybean became a tetraploid.

PMID- 22476037
TI  - High frequency spectral components after secobarbital: the contribution of
      muscular origin--a study with MEG/EEG.
AB  - OBJECTIVES: Previously we found that benzodiazepines not only provoke beta
      activity in the EEG, but also higher frequency activity. Knowing the origin of
      this high frequency activity is crucial if localisation of epileptogenic brain
      tissue is the query. We attempt to differentiate cerebral from muscular origin of
      such activity. METHODS: We postulate that EEG and MEG have similar sensitivity to
      brain activity, but different sensitivity to muscle activity, and compare co
      recorded EEG and MEG signals in a group of five patients who had received short
      lasting barbiturates to induce sleep. We performed principal components analysis
      over time and subtract the results for MEG from the EEG to see where the
      frequency spectra differ. RESULTS: The EEG showed activity in the gamma bands up
      to 270Hz for all patients; the MEG significantly less. We find no differences in
      the lower frequency bands. Topographically the differences localized over the
      frontotemporal regions. CONCLUSIONS: In the EEG benzodiazepines and/or
      barbiturates are not only associated with frequencies in the beta band, but also
      with wide range gamma activity. The latter seems to be of muscular origin.
      SIGNIFICANCE: Our study suggests that gamma activity in such measurements may not
      be cerebral in origin. MEG is less susceptible to contamination from muscle
      activity than the EEG.

PMID- 22476038
TI  - Recruitment for genetic studies of epilepsy.
AB  - Virtually nothing has been published about recruitment of adults with sporadic
      temporal lobe epilepsy (TLE) for genetic studies. We examined eligibility,
      recruitment, participation rates, and reasons for exclusion in a genetic study of
      TLE. Participants with non-acquired TLE with onset <=35 were recruited through
      review of records and screening of incoming patients at Columbia University
      Medical Center (CUMC). Eligible patients were asked to participate in an
      interview about seizures and give a blood sample for DNA extraction. Medical
      records were sought for each participant. Of 2974 patients screened 252 (8.5%)
      were eligible, and 40 (15.9% of eligible) participated. Leading reasons for
      ineligibility included an antecedent cause of epilepsy, syndrome other than TLE,
      and seizure onset after age 35. Those declining participation cited concerns
      about confidentiality, lack of compensation, and fear of phlebotomy. Although TLE
      is common and patients were recruited from a major surgical epilepsy center, a
      small proportion of potential participants participated. Large numbers need to be
      screened to reach the target sample size. Obtaining permission from treating
      physicians to contact their patients directly can improve recruitment. Saliva DNA
      collection, monetary incentives and patient education can improve participation.
      This information can facilitate study design in epilepsy genetics.

PMID- 22476039
TI  - Characterization of patients with low baseline impedance on multichannel
      intraluminal impedance-pH reflux testing.
AB  - GOALS: We aim to look at the prevalence of multichannel intraluminal impedance-pH
      (MII-pH) studies, which are difficult to interpret secondary to low distal
      baseline impedance (DBI), and characterize them by their respective diagnosis and
      DBI. BACKGROUND: Some patients exhibit low DBI because of fluid retention in the
      esophagus or acute or chronic mucosal changes. Low DBI can make MII-pH difficult
      to interpret. STUDY: We reviewed MII-pH reports from patients studied from
      January 2002 to December 2009. We conducted a computerized search of the final
      interpretation for the terms "low," "low baseline," "difficult," and "unable."
      Reflux reports stating difficult or unable to interpret were analyzed. The
      associated manometry studies were reviewed to obtain the DBI (mean value at 5 and
      10 cm above the lower esophageal sphincter in the pretest esophageal resting
      state). RESULTS: Of 2809 MII-pH tracings, 38 (1.4%) were classified as difficult
      to interpret because of low DBI. The most common underlying manometric diagnosis
      was ineffective esophageal motility at 36.8%, followed by 28.9% with achalasia,
      and 10.5% with scleroderma esophagus. An additional 15.8% of patients had
      increased gastroesophageal reflux on MII-pH. In only 7.9% of patients was no
      obvious reason for the low DBI identified. Of the 38 patients, 92% had a DBI
      <1000 Omega, and 58% had a DBI <500 Omega. CONCLUSIONS: These findings indicate
      that difficulty in interpreting MII-pH due to low baseline is very infrequent,
      and they suggest that it is unadvisable to perform MII-pH testing on patients
      with a DBI <500 Omega on prior MII-esophageal manometry. If needed, pH only
      testing off acid-suppressing therapy may be more advisable in these patients.

PMID- 22476040
TI  - Comparison of distribution of intraesophageal pH during nighttime recumbency
      among patients with gastroesophageal reflux disease.
AB  - BACKGROUND: Nighttime reflux has been demonstrated to be associated with a more
      aggressive presentation of gastroesophageal reflux disease (GERD). However, it
      has remained unknown until now if the difference in nighttime reflux between the
      different GERD groups is related to the distribution of intraesophageal pH level
      or duration of acid exposure. AIM: To compare distribution of intraesophageal pH
      during nighttime between patients with erosive esophagitis (EE) versus those with
      nonerosive reflux disease (NERD). METHODS: Patients with heartburn symptoms at
      least 3 times per week were included in this study. Patients were not receiving
      any antireflux treatment. All patients underwent an upper endoscopy to determine
      if esophageal inflammation was present or absent. Subsequently, patients
      underwent ambulatory 24-hour esophageal pH monitoring. Only those with NERD and
      EE were included in this study. Nighttime period was defined as the time from the
      moment patients entered the bed to fall asleep and until they woke up the next
      morning. Distribution of intraesophageal pH during nighttime was generated using
      a special computer program that analyzed all registered pH measurements. RESULTS:
      Nineteen patients were found to have NERD and 31 EE. Time in bed was not
      different between the 2 groups. The mean number of acid reflux events, mean
      reflux time pH<4, and mean % total time pH<4 during nighttime were significantly
      lower in the NERD group as compared with the EE group (13.05+/-4.6, 19.7+/-7.09,
      3.6+/-1.2% vs. 25.44+/-4.4, 29.3+/-7.97, 5.3+/-1.5%, respectively, all P<0.05).
      Symptom index for EE was 43.8% versus 21% for NERD, P<0.05. Overall, the
      distribution of intraesophageal pH during nighttime was similar between NERD and
      EE patients for all pH ranges. CONCLUSIONS: Patients with EE demonstrated a
      significantly higher nighttime esophageal acid exposure as compared with NERD,
      but the overall distribution of the acid exposure was similar between the 2
      groups. This suggests that duration rather than intensity of nighttime
      intraesophageal acid exposure accounts for the difference between EE and NERD.

PMID- 22476041
TI  - Obesity-independent association of human adenovirus Ad37 seropositivity with
      nonalcoholic fatty liver disease.
AB  - OBJECTIVE: Adenoviruses Ad36 and Ad37 increase adiposity in animals and are
      associated with obesity in humans; effects on the liver have been reported. The
      association of Adenovirus Ad36 seropositivity (Ad36+) with obesity but not with
      the severity of nonalcoholic fatty liver disease (NAFLD) has been previously
      shown. We investigate whether nondiabetic Ad37+ patients show a different
      prevalence of NAFLD and ultrasound Bright Liver score. PATIENTS: A total of 268
      adult nondiabetic patients (146 men, 122 women) were included after lifestyle
      counseling including a personalized Mediterranean diet, increase in physical
      activity, and smoking withdrawal. After an Ad37+/Ad36+ assay, overweight obesity,
      insulin resistance, C-reactive protein, and bright liver prevalence and severity
      were compared according to Ad37+. RESULTS: Sixty-five of 268 patients were Ad37+
      and 82/268 patients were both Ad37 seronegative (Ad37-) and Ad36-. The prevalence
      of obesity, defined as body mass index>=30, was not significantly different in
      Ad37+ (11/65; 16.9%) vs. Ad37- (15/82; 18.2%) patients; Bright Liver was present
      in 22/65 (33.8%) Ad37+ patients vs. 13/82 (15.8%) Ad37- patients (P<0.019). By
      odds ratio (OR), a consistent risk for NAFLD was associated with Ad37+, greater
      insulin resistance, and C-reactive protein. By a predictive multiple linear
      regression model, 40.0% of variance toward NAFLD and 50.4% toward the severity of
      Bright Liver score was explained significantly and independently by Ad37+ and by
      body mass index. CONCLUSIONS: Ad37+ status in nondiabetic patients on an
      appropriate diet is significantly associated with NAFLD; because fatty liver
      improves even without weight loss by a "healthy" diet, and not only by lower food
      caloric intake, Ad37+ may be an adjunctive hallmark of an unfavorable clinical
      metabolic profile, if not a causative factor of NAFLD.

PMID- 22476042
TI  - Immunoglobulin A deficiency in celiac disease.
AB  - GOALS: To determine the prevalence and significance of immunoglobulin A (IgA)
      deficiency and partial deficiency in patients with celiac disease (CD).
      BACKGROUND: Selective IgA deficiency is a common primary immunoglobulin
      deficiency and has a higher prevalence in patients with CD. The prevalence and
      significance of IgA deficiency and partial deficiency in patients with CD in the
      United States has not previously been examined. STUDY: A retrospective, cohort
      study of 1498 adults and 317 children seen in a University Medical Center was
      conducted. RESULTS: There were 26 patients (22 adults, 4 children) with CD who
      were IgA deficient and 11 (9 adults, 2 children) with CD who were partially IgA
      deficient. The prevalence of IgA deficiency/partial deficiency was similar among
      adults and children (2.1% and 1.9%, respectively, P=0.99). Among adults,
      concomitant autoimmune disease was present in 29% of IgA-deficient/partially
      deficient patients versus 12% of CD patients with normal IgA levels (P=0.0081).
      All 4 IgA-deficient patients who had persistently positive IgG celiac serologies
      while adherent to a gluten-free diet and were rebiopsied had a normal repeat
      biopsy. Both positive tissue transglutaminase IgG and antigliadin IgG were found
      in these patients. CONCLUSIONS: Selective IgA deficiency/partial deficiency is
      present in 2% of CD patients at this referral center and is equally prevalent
      among adults and children. IgA-deficient/partially deficient adults had a higher
      prevalence of concomitant autoimmune disease than those without IgA deficiency.
      In patients who are IgA deficient, IgG serologies may be persistently elevated
      despite histologic recovery.

PMID- 22476043
TI  - A survey of current practice of venous thromboembolism prophylaxis in
      hospitalized inflammatory bowel disease patients in the United States.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) patients are at an increased risk of
      thrombosis, particularly when hospitalized. Several clinical practice guidelines
      now recommend pharmacologic prophylaxis for hospitalized ulcerative colitis and
      Crohn's disease patients. It is unclear to what extent gastroenterologists are
      aware of these recommendations and whether they are administering pharmacologic
      venous thromboembolism (VTE) prophylaxis appropriately. Our aim was to explore
      current practice of VTE prophylaxis in hospitalized IBD patients in the United
      States. METHODS: A survey was mailed electronically to gastroenterologists whose
      electronic mail address was listed in the American College of Gastroenterology
      (ACG) database. This survey included clinical vignettes outlining scenarios for
      consideration of VTE prophylaxis. RESULTS: A total of 6227 surveys were sent to
      gastroenterologists nationwide, and 591 physicians chose to participate (response
      rate 9.5%). Respondents (80.6%) believed that hospitalized IBD patients have a
      higher risk of VTE than other inpatients. A total of 29.1% were unaware of any
      recommendations addressing pharmacologic prophylaxis included in ACG IBD
      guidelines and 34.6% would give pharmacologic VTE prophylaxis to a hospitalized
      patient with severe ulcerative colitis. Heparin VTE prophylaxis use was
      associated with gastroenterologists who indicated that their practices comprised
      more than 50% of patients with IBD (P=0.0001), being a physician at an academic
      hospital (P=0.0001) and providers having less than 5 years practice experience
      (P=0.003). CONCLUSIONS: Despite reasonable awareness of the increased risk of
      thrombosis in hospitalized IBD patients, many US gastroenterologists may not
      follow clinical practice guidelines and use pharmacologic VTE prophylaxis.

PMID- 22476044
TI  - Obese minorities have a higher prevalence of H. pylori than do whites, but
      nonsignificant differences in upper gastrointestinal tract findings, before
      laparoscopic adjustable gastric banding.

PMID- 22476045
TI  - Water channel proteins in the peripheral nervous system in health and disease.
AB  - The expression and function of aquaporins (AQPs) in the peripheral nervous system
      is a relatively under-investigated subject. Since the original description of
      AQP1 mRNA expression in the trigeminal ganglion in 2004, there has been
      significant progress in describing the expression, regulation and function of
      AQPs in the peripheral nervous system. Three out of the 13 mammalian AQPs (AQP1,
      AQP2 and AQP4) have been localized to neurons or glial cells in trigeminal
      ganglia, periodontal Ruffini endings, dorsal root ganglia and the enteric nervous
      system. Functional studies using knockout mice have suggested the involvement of
      AQP1 in peripheral pain perception. This review discusses current progress in
      this field and the possible involvement of AQPs in peripheral neuropathies.

PMID- 22476047
TI  - Combinatory effects of hepatic CD8+ and NK lymphocytes in bile duct injury from
      biliary atresia.
AB  - INTRODUCTION: To our knowledge, elucidating the immune pathogenesis of disease,
      especially characteristic T-cell and natural killer (NK) cell expansions, has not
      been performed before now. We investigated the role of T lymphocytes and NK
      lymphocytes in the destruction of extrahepatic bile ducts of patients with
      biliary atresia. METHODS: Lymphocytes from the liver and extrahepatic bile duct
      remnants of patients with biliary atresia were characterized by
      immunofluorescence staining, fluorescence-activated cell sorter analysis, and
      real-time reverse-transcriptase PCR. Cholangiocyte lysis assays were performed to
      confirm cytotoxicity of activated hepatic NK lymphocytes or CD8(+) cells.
      RESULTS: The inflammatory milieu from portal tracts and/or biliary remnants
      consisted of greater numbers of Kupffer cells, T lymphocytes, and NK lymphocytes
      in the patients with biliary atresia as compared with the cholestatic and
      noncholestatic controls. In patients with biliary atresia, expression of NK or
      CD8+ costimulatory molecules was upregulated as compared with controls. Hepatic
      NK lymphocytes or CD8(+) cells from patients with biliary atresia were
      demonstrated to be cytotoxic to the duct epithelium. DISCUSSION: Specific immune
      responses from NK and CD8(+) cells were involved in the injury to the duct
      epithelium and play a significant role in the phenotype of experimental biliary
      atresia.

PMID- 22476046
TI  - Effects of nonocclusive mesenteric hypertension on intestinal function:
      implications for gastroschisis-related intestinal dysfunction.
AB  - INTRODUCTION: Infants with gastroschisis (GS) have significant morbidity from
      dysmotility, feeding intolerance, and are at increased risk of developing
      intestinal failure. Although the molecular mechanisms regulating GS-related
      intestinal dysfunction (GRID) are largely unknown, we hypothesized that
      mechanical constriction (nonocclusive mesenteric hypertension (NMH)) from the
      abdominal wall defect acts as a stimulus for GRID. The purpose of this study was
      to determine the effect of NMH on intestinal function and inflammation. METHODS:
      Neonatal rats had placement of a silastic disk to the base of the mesentery (NMH)
      or no disk placement (Sham). At 24 and 72 h, mesenteric venous pressures (MVPs),
      intestinal transit, electric impedance, permeability, length, and tissue water
      content were measured. RESULTS: After placement of the silastic disk, there was a
      significant increase in MVP at both time points. There was also decreased
      intestinal transit. As compared to Sham animals, NMH animals had significant
      changes in bowel impedance without an increase in tissue water, suggesting
      significant intestinal remodeling. NMH rats had significantly increased smooth
      muscle thickness and loss of intestinal length as compared with Sham rats.
      DISCUSSION: NMH may be an initiating factor for GRID. Measurement of MVP and/or
      bowel impedance may be a way to assess severity and monitor progression and/or
      resolution of GRID.

PMID- 22476048
TI  - Regulation of epithelial immunity by IL-17 family cytokines.
AB  - Cutaneous and mucosal epithelial cells function as both a physical barrier and as
      immune sentinels against environmental challenges, such as microbial pathogens,
      allergens and stress. The crosstalk between epithelial cells and leukocytes is
      essential for orchestrating proper immune responses during host defense.
      Interleukin (IL)-17 family cytokines are important players in regulating innate
      epithelial immune responses. Although IL-17A and IL-17F promote antibacterial and
      antifungal responses, IL-17E is essential for defense against parasitic
      infections. Emerging data indicate that another member of this family, IL-17C,
      specifically regulates epithelial immunity. IL-17C production serves as an
      immediate defense mechanism by epithelial cells, utilizing an autocrine mechanism
      to promote antibacterial responses at barrier surfaces.

PMID- 22476050
TI  - Myoid angioendothelioma of the spleen mimicking metastatic disease in a patient
      with rectal cancer: a radiologic-pathologic correlation.
AB  - Myoid angioendothelioma of the spleen is an uncommon, benign vascular tumor that
      is morphologically characterized by a composite of vascular spaces and stromal
      cells with myoid feature. Herein, we report a case of the myoid angioendothelioma
      of the spleen, concurrent with rectal adenocarcinoma. A 41-year-old woman
      presented with hematochezia for several weeks. Grossly, the rectal mass was a 2.5
      * 2-cm ulcerative fungating lesion. The splenic mass was a 2.2 * 2-cm well
      circumscribed lesion. Microscopically, the rectal mass was a well-differentiated
      adenocarcinoma that invaded into the pericolic adipose tissue. The splenic mass
      was composed of slit-like vascular spaces and fascicles of elongated stromal
      cells. Vascular endothelial cells were immunopositive for CD31, factor VIII
      related antigen, and CD34 but negative for CD8. Stromal cells were immunopositive
      for smooth muscle actin but negative for desmin.

PMID- 22476049
TI  - A deep profiler's guide to cytometry.
AB  - In recent years, advances in technology have provided us with tools to quantify
      the expression of multiple genes in individual cells. The ability to measure
      simultaneously multiple genes in the same cell is necessary to resolve the great
      diversity of cell subsets, as well as to define their function in the host.
      Fluorescence-based flow cytometry is the benchmark for this; with it, we can
      quantify 18 proteins per cell, at >10 000 cells/s. Mass cytometry is a new
      technology that promises to extend these capabilities significantly.
      Immunophenotyping by mass spectrometry provides the ability to measure >36
      proteins at a rate of 1000 cells/s. We review these cytometric technologies,
      capable of high-content, high-throughput single-cell assays.

PMID- 22476051
TI  - The prognostic significance of nuclear CSE1L in urinary bladder urothelial
      carcinomas.
AB  - Prognosis of urinary bladder urothelial carcinomas may be challenging; many
      tumors with similar histopathologic features show significantly different
      clinical outcomes. CSE1L, the chromosome segregation 1-like protein, is both a
      cytoplasmic and nuclear protein. We investigated the cytoplasmic/nuclear
      expression pattern of CSE1L to determine its potential prognostic significance.
      In immunohistochemical analysis, nonneoplastic urothelium showed faint CSE1L
      staining, whereas all tumors in the bladder cancer specimens had significant
      staining for CSE1L (100%, or 38/38). CSE1L cytoplasmic/nuclear staining was
      defined based on relative staining intensity. A total of 20 (52.6%) of 38 cancer
      specimens had strong nuclear CSE1L staining, and 44.7.3% (17/38) of the samples
      had strong cytoplasmic CSE1L staining. Bladder urothelial carcinomas with high
      CSE1L nuclear staining had a significantly lower overall survival rate (log-rank
      test, P = .011). CSE1L expression was not correlated with tumor stage, likely
      reflecting the faultiness of current urothelial carcinoma evaluation methods. Our
      results suggest that nuclear CSE1L may play an oncogenic role in bladder tumor
      progression and that immunohistochemical staining of nuclear CSE1L may be useful
      for the prognosis of bladder urothelial carcinomas.

PMID- 22476053
TI  - Antibody affinity purification using metallic nickel particles.
AB  - Functionalized magnetic particles are emerging as a reliable and convenient
      technique in the purification of biomacromolecules (proteins and nucleic acids)
      and cell separation. In this study, we used novel solid nickel ferromagnetic
      particles coated with Protein A for the affinity purification of antibody. The
      study demonstrated that IgG can be purified from undiluted mouse serum in as few
      as 5 min using Protein A-coated nickel particles. Further, protein crosslinking
      was shown to stabilize the Protein A on the nickel particle surfaces to minimize
      Protein A leaching during the affinity purification and elution of IgG. The
      separation procedure is gentle, scalable, automatable, efficient and economical.
      By modifying the functional groups of amino acids in the protein coating,
      crosslinked nickel particles can be used not only for protein affinity
      purification but for other biological sample preparation and chromatographic
      applications as well. Methods proposed and tested in this study can be easily
      modified for small and medium scale antibody purification in lab and pre-clinical
      research.

PMID- 22476052
TI  - Simultaneous determination of 45 pesticides in fruit and vegetable using an
      improved QuEChERS method and on-line gel permeation chromatography-gas
      chromatography/mass spectrometer.
AB  - In this study, a method was developed to determine 45 selected pesticides (of
      different chemical families) in fruit and vegetable (including apple, spinach and
      cucumber). Samples were extracted using an improved QuEChERS method with salting
      out and phase separation in two steps. The target pesticides in concentrated
      extracts were analyzed by an on-line gel permeation chromatography-gas
      chromatography/mass spectrometer (online-GPC-GC/MS). Online GPC effectively
      removed matrix interferences and greatly improved the method sensitivity,
      recoveries and automation. Method limits of quantification were 10 ng/g for
      uniconazole and metalaxyl, and 5 ng/g for other 43 target analytes. In three
      fruit and vegetable matrices each spiked with 45 pesticides (0.01 MUg/g), mean
      recoveries ranged from 80 to 118% for most of the tested pesticides except for
      profenofos (77% in apple) and chlorpyrifos (68% in apple and 75% in cucumber),
      with relative standard deviations (RSDs) of less than 14%. The results of the
      proficiency testing showed that the method is very successful in measuring the
      certified pesticides with less than 1.3 of the absolute value of Z-score. This
      method has been applied for routinely monitoring pesticides in fresh fruit and
      vegetable.

PMID- 22476054
TI  - Liquid chromatography-tandem mass spectrometric assay for the JAK2 inhibitor
      CYT387 in plasma.
AB  - A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC
      MS/MS) assay for the JAK2 inhibitor CYT387 was developed and validated. Plasma
      samples were pre-treated using protein precipitation with acetonitrile containing
      cediranib as internal standard. The extract was directly injected into the
      chromatographic system after dilution with water. This system consisted of a sub
      2 MUm particle, trifunctional bonded octadecyl silica column with a gradient
      using 0.005% (v/v) of formic acid in a mixture of water and methanol. The eluate
      was transferred into the electrospray interface with positive ionization and the
      analyte was detected in the selected reaction monitoring mode of a triple
      quadrupole mass spectrometer. The assay was validated in a 0.25-1000 ng/ml
      calibration range. Within day precisions were 3.0-13.5%, between day precisions
      5.7% and 14.5%. Accuracies were between 96% and 113% for the whole calibration
      range. The drug was stable under all relevant analytical conditions. Finally, the
      assay was successfully used to assess drug levels in mice.

PMID- 22476055
TI  - Liquid chromatography-tandem mass spectrometric assay for the VEGFR inhibitor
      cediranib and its primary human metabolite cediranib-N+-glucuronide in plasma.
AB  - A quantitative bioanalytical assay for cediranib and its N(+)-glucuronide
      metabolite was developed and validated. Human plasma samples were pre-treated
      using protein precipitation with acetonitrile containing erlotinib and CYT-387 as
      internal standards for the glucuronide metabolite and parent compound,
      respectively. The extract was diluted with water and injected into the
      chromatographic system. This system consisted of sub-2 MUm particles, a
      trifunctional bonded octadecyl silica column with gradient elution using 0.005%
      (v/v) of formic acid in a mixture of water and methanol. The eluate was
      transferred into the electrospray interface with positive ionization and the
      analytes were detected in the selected reaction monitoring mode of a triple
      quadrupole mass spectrometer. The assay was validated in a 1-290 ng/ml
      calibration range for cediranib and 0.2-52 ng/ml for its glucuronide metabolite.
      The lowest levels of these ranges corresponded to the lower limits of
      quantification for both compounds. Within day precisions were 4.0-6.7% for
      cediranib and 4.1-11.9% for its glucuronide, between day precisions were 4.2-10.2
      and 4.8-14.4% and accuracies were between 99 and 106 and 84 and 94% for cediranib
      and its metabolite, respectively. Stabilities of both compounds were sufficient
      under all relevant conditions. Finally, the assay was successfully used to assess
      drug levels in a pharmacokinetic mouse study.

PMID- 22476056
TI  - Localized growth and in situ integration of nanowires for device applications.
AB  - Simultaneous localized growth and device integration of inorganic nanostructures
      on heated micromembranes is demonstrated for single crystalline germanium and tin
      oxide nanowires. Fully operating CO gas sensors prove the potential of the
      presented approach. With this simple CMOS compatible technique, issues of
      assembly, transfer and contact formation are addressed.

PMID- 22476057
TI  - Dynamics of AHL mediated quorum sensing under flow and non-flow conditions.
AB  - Quorum sensing (QS) describes the capability of microbes to communicate with each
      other by the aid of small molecules. Here we investigate the dynamics of QS
      regulated gene expression induced by acylhomoserine lactones (AHLs) in
      Pseudomonas putida IsoF containing a green fluorescent protein-based AHL
      reporter. The fluorescence time course of individual colonies is monitored
      following the external addition of a defined AHL concentration to cells which had
      previously reached the QS-inactive state in AHL-free medium. Using a microfluidic
      setup the experiment is performed both under flow and non-flow conditions. We
      find that without supplying external AHL gene expression is induced without flow
      while flow suppresses the induction. Both without and with flow, at a low AHL
      concentration the fluorescence onset is significantly delayed while fluorescence
      starts to increase directly upon the addition of AHL at a high concentration. The
      differences between no flow and flow can be accounted for using a two-compartment
      model. This indicates AHL accumulation in a volume which is not affected by the
      flow. The experiments furthermore show significant cell-to-cell and colony-to
      colony variability which is discussed in the context of a compartmentalized QS
      mechanism.

PMID- 22476058
TI  - The message in the air: hydrogen sulfide metabolism in chronic respiratory
      diseases.
AB  - Hydrogen sulfide (H(2)S) is an important gasotransmitter in the mammalian
      respiratory system. The enzymes that produce H(2)S - mainly cystathionine-beta
      synthase and cystathionine-gamma-lyase - are expressed in pulmonary and airway
      tissues. Endogenous H(2)S participates in the regulation of the respiratory
      system's physiological functions and pathophysiological alterations, such as
      chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and hypoxia
      induced pulmonary hypertension, to name a few. The cellular targets of H(2)S in
      the respiratory system are diverse, including airway smooth muscle cells,
      epithelial cells, fibroblasts, and pulmonary artery smooth muscle cells. H(2)S
      also regulates respiratory functions such as airway constriction, pulmonary
      circulation, cell proliferation or apoptosis, fibrosis, oxidative stress, and
      neurogenic inflammation. Cross-talk between H(2)S and other gasotransmitters also
      affects the net outcome of lung function. The metabolism of H(2)S in the lungs
      and airway may serve as a biomarker for specific respiratory diseases. It is
      expected that strategies targeted at the metabolism and function of H(2)S will
      prove useful for the prevention and treatment of selective chronic respiratory
      diseases.

PMID- 22476059
TI  - A new antihypertensive drug ameliorate insulin resistance.

PMID- 22476060
TI  - Sodium nitroprusside-mediated alleviation of iron deficiency and modulation of
      antioxidant responses in maize plants.
AB  - BACKGROUND AND AIMS: Nitric oxide (NO) has been reported to alleviate Fe
      deficiency effects, possibly by enhancing the functional Fe status of plants.
      This study examines changes in tissue Fe status and oxidative metabolism in Fe
      deficient maize (Zea mays L.) plants enriched with NO using sodium nitroprusside
      (SNP) as a source. METHODOLOGY: Measurements included changes in concentrations
      of H(2)O(2), non-protein thiols, levels of lipid peroxidation and activities of
      superoxide dismutase (SOD) and of the Fe-requiring antioxidant haem enzymes
      catalase, peroxidase and ascorbate peroxidases. Internal NO in Fe-deficient maize
      plants was manipulated with SNP and the NO scavenger, methylene blue (MB). A key
      control was treatment with sodium ferrocyanide (SF), a non-NO-supplying analogue
      of SNP. PRINCIPAL RESULTS: SNP but not SF caused re-greening of leaves in Fe
      deficient maize plants over 10-20 days, increased in vivo NO content, raised
      chlorophyll and carotenoid concentrations, promoted growth in dry weight,
      increased the activities of H(2)O(2)-scavenging haem enzymes and enhanced lipid
      peroxidation, while decreasing SOD activity and H(2)O(2) concentrations. The NO
      scavenger, MB, blocked the effects of the SNP. Although SNP and SF each donated
      Fe and increased active Fe, only SNP increased leaf chlorophyll. CONCLUSIONS: NO
      plays a role in Fe nutrition, independently of its effect on total or active Fe
      status. The most probable mechanism of NO involvement is to increase the
      intracellular availability of Fe by means of modulating redox. This is likely to
      be achieved by enhancing the chemical reduction of foliar Fe(III) to Fe(II).

PMID- 22476061
TI  - Struggle in the flood: tree responses to flooding stress in four tropical
      floodplain systems.
AB  - BACKGROUND AND AIMS: In the context of the 200th anniversary of Charles Darwin's
      birth in 1809, this study discusses the variation in structure and adaptation
      associated with survival and reproductive success in the face of environmental
      stresses in the trees of tropical floodplains. SCOPE: We provide a comparative
      review on the responses to flooding stress in the trees of freshwater wetlands in
      tropical environments. The four large wetlands we evaluate are: (i) Central
      Amazonian floodplains in South America, (ii) the Okavango Delta in Africa, (iii)
      the Mekong floodplains of Asia and (iv) the floodplains of Northern Australia.
      They each have a predictable 'flood pulse'. Although flooding height varies
      between the ecosystems, the annual pulse is a major driving force influencing all
      living organisms and a source of stress for which specialized adaptations for
      survival are required. MAIN POINTS: The need for trees to survive an annual flood
      pulse has given rise to a large variety of adaptations. However, phenological
      responses to the flood are similar in the four ecosystems. Deciduous and
      evergreen species respond with leaf shedding, although sap flow remains active
      for most of the year. Growth depends on adequate carbohydrate supply.
      Physiological adaptations (anaerobic metabolism, starch accumulation) are also
      required. CONCLUSIONS: Data concerning the ecophysiology and adaptations of trees
      in floodplain forests worldwide are extremely scarce. For successful floodplain
      conservation, more information is needed, ideally through a globally co-ordinated
      study using reproducible comparative methods. In the light of climatic change,
      with increasing drought, decreased groundwater availability and flooding
      periodicities, this knowledge is needed ever more urgently to facilitate fast and
      appropriate management responses to large-scale environmental change.

PMID- 22476062
TI  - Morphological, photosynthetic and water relations traits underpin the contrasting
      success of two tropical lichen groups at the interior and edge of forest
      fragments.
AB  - BACKGROUND AND AIMS: Forest edges created by fragmentation strongly affect the
      abiotic and biotic environment. A rarely studied consequence is the resulting
      impact on non-vascular plants such as poikilohydric lichens, known to be highly
      sensitive to changes in the microenvironment. We evaluated the impact of forest
      edge and forest interior on the distribution of two groups of crustose lichens
      characterized by the presence or absence of a cortex and sought explanations of
      the outcome in terms of photosynthetic response and water relations. METHODOLOGY:
      Microclimate, distribution patterns and physiology of cortical and non-cortical
      lichens were compared at the edge and in the interior of an Atlantic rainforest
      fragment in Alagoas, Brazil. Ecophysiological aspects of photosynthesis and water
      relations were studied using chlorophyll a fluorescence analysis, and hydration
      and rehydration characteristics. PRINCIPAL RESULTS: Cortical and non-cortical
      functional groups showed a clear preference for interior and edge habitats,
      respectively. The cortical lichens retained liquid water more efficiently and
      tolerated low light. This explains their predominance in the forest interior,
      where total area cover on host tree trunks reached ca. 40 % (versus ca. 5 % for
      non-cortical lichens). Although non-cortical lichens exchanged water vapour
      efficiently, they required high light intensities. Consequently, they were able
      to exploit well-lit edge conditions where they achieved an area cover of ca. 19 %
      (versus ca. 7 % for cortical lichens). We provide some of the first data for
      lichens giving the relative quantity of incident light absorbed by the
      photosystem (absorptivity). The cortical group achieved higher absorptivity and
      quantum efficiencies, but at the expense of physiological plasticity; non
      cortical lichens showed much decreased values of F(v)/F(m) and electron transport
      rates in the forest interior. CONCLUSIONS: Morphological and physiological
      features largely determine the ecophysiological interaction of lichen functional
      groups with their abiotic environment and, as a consequence, determine their
      habitat preference across forest habitats. In view of the distinctiveness of
      their distribution patterns and ecophysiological strategies, the occurrence of
      cortical versus non-cortical lichens can be a useful indicator of undisturbed
      forest interiors in tropical forest fragments.

PMID- 22476063
TI  - Ability of crassulacean acid metabolism plants to overcome interacting stresses
      in tropical environments.
AB  - BACKGROUND AND AIMS: Single stressors such as scarcity of water and extreme
      temperatures dominate the struggle for life in severely dry desert ecosystems or
      cold polar regions and at high elevations. In contrast, stress in the tropics
      typically arises from a dynamic network of interacting stressors, such as
      availability of water, CO(2), light and nutrients, temperature and salinity. This
      requires more plastic spatio-temporal responsiveness and versatility in the
      acquisition and defence of ecological niches. CRASSULACEAN ACID METABOLISM: The
      mode of photosynthesis of crassulacean acid metabolism (CAM) is described and its
      flexible expression endows plants with powerful strategies for both acclimation
      and adaptation. Thus, CAM plants are able to inhabit many diverse habitats in the
      tropics and are not, as commonly thought, successful predominantly in dry, high
      insolation habitats. TROPICAL CAM HABITATS: Typical tropical CAM habitats or
      ecosystems include exposed lava fields, rock outcrops of inselbergs, salinas,
      savannas, restingas, high-altitude paramos, dry forests and moist forests.
      MORPHOTYPICAL AND PHYSIOTYPICAL PLASTICITY OF CAM: Morphotypical and
      physiotypical plasticity of CAM phenotypes allow a wide ecophysiological
      amplitude of niche occupation in the tropics. Physiological and biochemical
      plasticity appear more responsive by having more readily reversible variations in
      performance than do morphological adaptations. This makes CAM plants particularly
      fit for the multi-factor stressor networks of tropical forests. Thus, while the
      physiognomy of semi-deserts outside the tropics is often determined by tall
      succulent CAM plants, tropical forests house many more CAM plants in terms of
      quantity (biomass) and quality (species diversity).

PMID- 22476064
TI  - Effect of salinity on water relations of wild barley plants differing in salt
      tolerance.
AB  - BACKGROUND AND AIMS: Certain lines of wild barley (Hordeum spontaneum) are more
      tolerant of salinity than others. The physiological basis of this difference is
      examined in a comparative study of a saline-tolerant and saline-intolerant line
      that emphasizes plant water relations. METHODOLOGY: Effects of salt-treatment (75
      mM maximum) extending from a few hours to 3 weeks were quantified in 8-day-old
      seedlings of a saline-sensitive wild barley line ('T-1') and a less saline
      sensitive line ('20-45'). Plants were grown in nutrient culture. Levels of mRNA
      of the HtPIP2;4 aquaporin (AQP) gene were determined together with a range of
      physiological responses including root hydraulic conductivity, osmotic potential
      of root xylem sap, transpiration, leaf relative water content, root water
      content, leaf water potential, leaf sap osmolality, leaf length, leaf area and
      chlorophyll content. PRINCIPAL RESULTS: Salt treatment inhibited transpiration
      and hydraulic conductivity more in salt-tolerant '20-45' plants than in salt
      sensitive 'T-1'. In '20-45', the effect was paralleled by a fast (within a few
      hours) and persistent (3 days) down-regulation of aquaporin. In salt-sensitive 'T
      1' plants, aquaporin down-regulation was delayed for up to 24 h. Greater
      tolerance in '20-45' plants was characterized by less inhibition of leaf area,
      root fresh weight, leaf water content and chlorophyll concentration. Leaf water
      potentials were similar in both lines. CONCLUSIONS: (i) Decline in hydraulic
      conductivity in salt-treated barley plants is important for stomatal closure,
      (ii) lowered transpiration rate is beneficial for salt tolerance, at least at the
      seedling stage and (iii) changes in AQP expression are implicated in the control
      of whole plant hydraulic conductivity and the regulation of shoot water
      relations.

PMID- 22476065
TI  - Nucleated succession by an endemic palm Phoenix pusilla enhances diversity of
      woody species in the arid Coromandel Coast of India.
AB  - BACKGROUND AND AIMS: Phoenix pusilla, an endemic shrubby palm, was used as a
      model nurse plant in degraded tropical dry evergreen forest (TDEF) landscapes.
      This choice was informed by traditional ecological knowledge of the Irula tribe
      of south India. We tested whether the presence of P. pusilla in water-stressed
      arid regions improves conditions for other species to establish, resulting in
      nucleated succession. Success would point the way forward for establishing
      species-rich woodland in abandoned farm land on the south-eastern Coromandel
      Coast of India. METHODOLOGY: Spatial associations of woody species in the natural
      landscape were studied. Experimental tests of nurse plant potential examined the
      extent to which P. pusilla (i) promoted seed germination, (ii) seedling emergence
      and (iii) establishment of two TDEF species, and (iv) ameliorated soil and
      microclimatic conditions over 8 months. PRINCIPAL RESULTS: Phoenix pusilla cooled
      the soil by up to 50 % and decreased radiation by up to 9-fold, especially in
      summer. Soil organic matter and water-holding capacity increased, as did seedling
      number and seedling height of tested TDEF species. The presence of P. pusilla
      favoured a greater abundance (20 %) of woody plants with a bias towards primary
      (11) rather than secondary (2) species, indicating species specificity of the
      effect. CONCLUSIONS: Phoenix pusilla ameliorated abiotic stresses present in open
      ground to create a patchy species-rich mosaic. This nucleated succession created
      using P. pusilla provided an important refuge for primary TDEF species. This
      effect can be expected to have impact at the landscape scale and may prove useful
      in managing landscapes and in biodiversity conservation. The conservation value
      of these patchy landscapes deserves to be more widely recognized as they persist
      in populated areas and thus merit protection. The value of traditional tribal
      knowledge in identifying a highly effective nurse species is highlighted by this
      study.

PMID- 22476066
TI  - Multifunctional crop trait ontology for breeders' data: field book, annotation,
      data discovery and semantic enrichment of the literature.
AB  - BACKGROUND AND AIMS: Agricultural crop databases maintained in gene banks of the
      Consultative Group on International Agricultural Research (CGIAR) are valuable
      sources of information for breeders. These databases provide comparative
      phenotypic and genotypic information that can help elucidate functional aspects
      of plant and agricultural biology. To facilitate data sharing within and between
      these databases and the retrieval of information, the crop ontology (CO) database
      was designed to provide controlled vocabulary sets for several economically
      important plant species. METHODOLOGY: Existing public ontologies and equivalent
      catalogues of concepts covering the range of crop science information and
      descriptors for crops and crop-related traits were collected from breeders,
      physiologists, agronomists, and researchers in the CGIAR consortium. For each
      crop, relationships between terms were identified and crop-specific trait
      ontologies were constructed following the Open Biomedical Ontologies (OBO) format
      standard using the OBO-Edit tool. All terms within an ontology were assigned a
      globally unique CO term identifier. PRINCIPAL RESULTS: The CO currently comprises
      crop-specific traits for chickpea (Cicer arietinum), maize (Zea mays), potato
      (Solanum tuberosum), rice (Oryza sativa), sorghum (Sorghum spp.) and wheat
      (Triticum spp.). Several plant-structure and anatomy-related terms for banana
      (Musa spp.), wheat and maize are also included. In addition, multi-crop passport
      terms are included as controlled vocabularies for sharing information on
      germplasm. Two web-based online resources were built to make these COs available
      to the scientific community: the 'CO Lookup Service' for browsing the CO; and the
      'Crops Terminizer', an ontology text mark-up tool. CONCLUSIONS: The controlled
      vocabularies of the CO are being used to curate several CGIAR centres' agronomic
      databases. The use of ontology terms to describe agronomic phenotypes and the
      accurate mapping of these descriptions into databases will be important steps in
      comparative phenotypic and genotypic studies across species and gene-discovery
      experiments.

PMID- 22476067
TI  - Plant reproduction in the Central Amazonian floodplains: challenges and
      adaptations.
AB  - BACKGROUND: The Central Amazonian floodplain forests are subjected to extended
      periods of flooding and to flooding amplitudes of 10 m or more. The
      predictability, the length of the flood pulse, the abrupt transition in the
      environmental conditions along topographic gradients on the banks of major rivers
      in Central Amazonia, and the powerful water and sediment dynamics impose a strong
      selective pressure on plant reproduction systems. SCOPE: In this review, we
      examine how the hydrological cycle influences the strategies of sexual and
      asexual reproduction in herbaceous and woody plants. These are of fundamental
      importance for the completion of the life cycle. Possible constraints to seed
      germination, seedling establishment and formation of seed banks are also covered.
      Likewise, we also discuss the importance of river connectivity for species
      propagation and persistence in floodplains. CONCLUSIONS: The propagation and
      establishment strategies employed by the highly diversified assortment of
      different plant life forms result in contrasting successional stages and a
      zonation of plant assemblages along the flood-level gradient, whose species
      composition and successional status are continuously changing not only temporally
      but also spatially along the river channel.

PMID- 22476068
TI  - Morphological and physiological responses of lowland purple nutsedge (Cyperus
      rotundus L.) to flooding.
AB  - BACKGROUND AND AIMS: Purple nutsedge (Cyperus rotundus L.) is a major weed of
      upland crops and vegetables. Recently, a flood-tolerant ecotype evolved as a
      serious weed in lowland rice. This study attempted to establish the putative
      growth and physiological features that led to this shift in adaptation.
      METHODOLOGY: Tubers of upland C. rotundus (ULCR) and lowland C. rotundus (LLCR)
      ecotypes were collected from their native habitats and maintained under the
      respective growth conditions in a greenhouse. Five experiments were conducted to
      assess the variation between the two ecotypes in germination, growth and tuber
      morphology when grown in their native or 'switched' conditions. Carbohydrate
      storage and mobilization, and variation in anaerobic respiration under hypoxia
      were compared. PRINCIPAL RESULTS: Tubers of LLCR were larger than those of ULCR,
      with higher carbohydrate content, and larger tubers developed with increasing
      floodwater depth. Stems of LLCR had larger diameter and proportionally larger air
      spaces than those of ULCR: a method of aerating submerged plant parts. The LLCR
      ecotype can also mobilize and use carbohydrate reserves under hypoxia, and it
      maintained relatively lower and steadier activity of alcohol dehydrogenase (ADH)
      as a measure of sustained anaerobic respiration. In contrast, ADH activity in
      ULCR increased faster upon a shift to hypoxia and then sharply decreased,
      suggesting depletion of available soluble sugar substrates. The LLCR ecotype also
      maintained lower lactate dehydrogenase activity under flooded conditions, which
      could reduce chances of cellular acidosis. CONCLUSIONS: These adaptive traits in
      the LLCR ecotype were expressed constitutively, but some of them, such as tuber
      growth and aerenchyma development, are enhanced with stress severity. The LLCR
      ecotype attained numerous adaptive traits that could have evolved as a
      consequence of natural evolution or repeated management practices, and
      alternative strategies are necessary because flooding is no longer a feasible
      management option.

PMID- 22476069
TI  - Strong positive growth responses to salinity by Ceriops tagal, a commonly
      occurring mangrove of the Gujarat coast of India.
AB  - BACKGROUND AND AIMS: Mangroves of Western Gujarat (India) are subject to die
      back. Salinity intolerance is one possible cause, especially in young plants. We
      therefore quantified the extent to which young plants of one widely occurring
      mangrove species (Ceriops tagal) tolerate high salt in terms of establishment,
      growth, water status, proline content and mineral accumulation. METHODOLOGY: In a
      greenhouse study, juvenile plants were established from mature propagules over 40
      days in soil containing added NaCl, raising soil water salinity to 0.2, 2.5, 5.1,
      7.7, 10.3, 12.6, 15.4, 17.9, 20.5 and 23.0 ppt (w/v). Growth and physiological
      characteristics were monitored over the subsequent 6 months. PRINCIPAL RESULTS:
      Despite a negative relationship between the percentage of young plant
      establishment and salt concentration (50 % loss at 22.3 ppt), the remaining
      plants proved highly tolerant. Growth, in dry weight, was significantly promoted
      by low salinity, which is optimal at 12.6 ppt. Water content, leaf expansion and
      dry matter accumulation in tissues followed a similar optimum curve with leaf
      area being doubled at 12.6 ppt NaCl. Salinity >12.6 and <23 ppt inhibited plant
      growth, but never to below control levels. Root:shoot dry weight ratios were
      slightly reduced by salinity (maximum 19 %), but the water potential of roots,
      leaves and stems became more negative as salinity increases while proline
      increases in all tissues. The concentration of Na increased, whereas
      concentrations of K, Ca, N and P decreased and that of Mg remained stable.
      CONCLUSIONS: Ceriops tagal has a remarkably high degree of salinity tolerance,
      and shows an optimal growth when soil water salinity is 12.6 ppt. Salinity
      tolerance is linked to an adaptive regulation of hydration and ionic content. The
      cause of localized die-back along the coastal region of Gujarat is thus unlikely
      to be a primary outcome of salinity stress although amendments with Ca and K, and
      perhaps proline, may help protect against extreme salinity.

PMID- 22476070
TI  - Bolting and flowering control in sugar beet: relationships and effects of
      gibberellin, the bolting gene B and vernalization.
AB  - BACKGROUND AND AIMS: Bolting, the first visible sign of reproductive transition
      in beets (Beta vulgaris), is controlled by the dominant bolting gene B (B
      allele), which allows for flowering under long days (LDs, >14 h light) without
      prior vernalization. The B-locus carries recessive alleles (bb) in sugar beet
      (Beta vulgaris L. spp. vulgaris), so that vernalization and LDs are required for
      bolting and flowering. Gibberellin growth hormones (GAs) control stem elongation
      and reproductive development, but their role during these processes in sugar beet
      is not defined. We aimed to investigate the involvement of GAs in bolting and
      flowering in sugar beet, and also its relationship with the vernalization
      requirement as defined by the B-gene. METHODOLOGY: Plants segregating for the B
      allele were treated with exogenous GA(4) under inductive (16 h light) and non
      inductive (8 h light) photoperiods, with and without prior vernalization
      treatment. A co-dominant polymerase chain reaction (PCR) marker was used to
      genotype the B-gene locus. Bolting and flowering dates were scored, and bolt
      heights were measured as appropriate. Analysis of variance was used to determine
      the effects and interactions of GAs, the B allele and vernalization on bolting
      and flowering. The effects of the B allele on bolting were also verified in the
      field. PRINCIPAL RESULTS: Application of GAs or the B allele could initiate
      bolting independently. When the B allele was absent, the applied GAs promoted
      stem growth, but did so only in vernalized plants, irrespective of photoperiod.
      Under LDs, bolt height before flowering in plants carrying the B allele (BB; Bb)
      was not significantly influenced by GAs. The timing and frequency of flowering
      were influenced by the B allele without interactive effects from GAs.
      CONCLUSIONS: In sugar beet, GA acts independently of the B allele and photoperiod
      to induce bolting. Vernalization enables GA action independently of the B allele;
      hence, the dominant B allele may not directly participate in vernalization
      induced bolting.

PMID- 22476071
TI  - Interactions between rootstock, inter-stem and scion xylem vessel characteristics
      of peach trees growing on rootstocks with contrasting size-controlling
      characteristics.
AB  - BACKGROUND AND AIMS: The primary physiological mechanism influencing tree vigour
      in size-controlling rootstocks of peach has been related to the hydraulic
      conductance of the rootstock. Differences in rootstock hydraulic conductance are
      a function of rootstock xylem vessel characteristics. The present research
      examined whether the vigour and xylem vessel characteristics of the rootstock
      influence the xylem characteristics of the scion. We tested whether using a size
      controlling rootstock genotype as an inter-stem influences the xylem vessel
      characteristics of either the rootstock below the inter-stem or the scion above
      it and vice versa. METHODOLOGY: Anatomical measurements (diameter and frequency)
      of xylem vessels were determined above and below the graft unions of the trunks
      of peach trees with differing scion/rootstock combinations. The three peach
      rootstocks were 'Nemaguard' (vigorous), 'P30-135' (intermediate vigour) and 'K146
      43' (dwarfing). The vigorous scion cultivar was 'O'Henry'. The inter-stem
      experiment involved trees with 'Nemaguard' (vigorous) as the rootstock, 'K146-43'
      (dwarfing) as the inter-stem and 'O'Henry' as the scion. Based on anatomical
      measurements, we calculated the theoretical axial xylem conductance of each stem
      piece and rootstock genotype with the Hagen-Poiseuille law. PRINCIPAL RESULTS:
      Xylem vessel dimensions of rootstocks varied in conjunction with tree vigour.
      Scion xylem vessel dimensions of different scion/rootstock combinations were only
      marginally affected by rootstock genotype. The inter-stem sections from the
      dwarfing genotype ('K146-43') had narrower vessels and a lower calculated
      hydraulic conductance than the xylem from either the vigorous rootstock below
      ('Nemaguard') or the scion above ('O'Henry'). CONCLUSIONS: Rootstock genotype
      only marginally affected scion xylem vessel characteristics. Thus the xylem
      vessel characteristics of the dwarfing rootstock genotypes appear to influence
      tree growth directly rather than through an effect on the xylem characteristics
      of the scion. A dwarfing rootstock genotype used as an inter-stem appeared to
      work as a physical restriction to water movement, reducing potential xylem flow
      and conductance of the whole tree.

PMID- 22476072
TI  - Nitrification inhibition activity, a novel trait in root exudates of rice.
AB  - BACKGROUND AND AIMS: Nitrification is an important process in soil--plant systems
      for providing plant-available nitrate (NO(3) (-)). However, NO(3) (-) is less
      stable in soils compared with ammonium (NH(4) (+)) and is more easily lost
      through leaching, runoff or denitrification. This study tested whether biological
      nitrification inhibition (BNI) activity is present in the root exudates of rice
      (Oryza sativa) and also the extent of variation between different genotypes.
      METHODOLOGY: The BNI activity of root exudates was estimated by a bioluminescence
      assay using a recombinant Nitrosomonas europaea strain. Afterwards, the effect of
      a single application of concentrated root exudates and that of exudates deposited
      in the rhizosphere soil was tested on BNI using soil incubation. Soil was added
      with (NH(4))(2)SO(4) and water to reach 60 % of the water-holding capacity and
      incubated at 30  degrees C for different periods. Amounts of NH(4) (+) and NO(3)
      (-) were determined using a continuous-flow auto-analyser. PRINCIPAL RESULTS: In
      an initial screening experiment, BNI activity in the exudates of 36 different
      rice genotypes was evaluated using a bioassay based on a recombinant Nitrosomonas
      strain. Significant genotypic variation was detected with the upland cultivar
      IAC25 demonstrating consistently high BNI activity, while modern lowland
      varieties like Nipponbare or IR64 exhibited lower activity. Subsequent
      experiments ruled out the possibility that BNI activity is simply due to non
      specific (solute) leakage from roots. Soil incubation studies with concentrated
      root exudates of IAC25 showed significant reductions in NO(3) (-) formation. This
      effect was confirmed by detecting lower NO(3) (-) levels in incubation
      experiments using rhizosphere soil obtained from IAC25. CONCLUSIONS: Our results
      provide first evidence that root exudates of rice can reduce nitrification rates
      in soil. Having shown this for a model crop, rice, offers possibilities for
      further exploitation of this phenomenon through molecular and genetic tools.

PMID- 22476073
TI  - Genome size variation in diploid and tetraploid wild wheats.
AB  - BACKGROUND AND AIMS: Intra- and interspecific variations of C-values and the
      relationship between habitat factors and genome size were studied in natural
      populations of diploid and tetraploid wild wheats. METHODOLOGY: The 1C nuclear
      DNA content of 376 individual plants representing 41 populations of diploid and
      tetraploid wild wheats was determined by flow cytometry (FCM) and correlated with
      geographical and bioclimate variables. PRINCIPAL RESULTS: Based on analysis of
      variance, significant differences between diploid and tetraploid Triticum species
      were found. Differences among populations of T. boeoticum and T. dicoccoides were
      also statistically significant and argue for isolation between populations,
      except for T. araraticum. However, the variation among individuals of the same
      population was not statistically significant. Maximum genome size differences
      among populations for T. boeoticum (0.143 pg; 2.32 %), T. dicoccoides (0.314 pg;
      2.49 %) and T. araraticum (0.116 pg; 0.98 %) argue for genome constancy in these
      species. There was no significant correlation between intra-population variance
      and geographical and bioclimate variables for T. boeoticum and T. dicoccoides. In
      contrast to the limited genome size variation at the intraspecific level, the
      interspecific variation was large: ~0.5 pg/1C (8 %) at the diploid level (T.
      boeoticum vs. T. urartu) and ~1 pg/1C (9.7 %) at the tetraploid level (T.
      dicoccoides vs. T. araraticum). CONCLUSIONS: Low intraspecific genome size
      variation occurs in diploid and tetraploid wild wheats, and this limited
      variation is not correlated with geographical and climate variables. However,
      interspecific variation is significant at the diploid and tetraploid level. It
      can be concluded that the genome size of wild self-fertilizing Triticum species
      is generally stable, despite the presence of many potentially active
      retroelements. In natural habitats, it is very difficult to distinguish wild
      wheats from each other. However, all four species can be distinguished easily,
      quickly and unambiguously by using the FCM technique.

PMID- 22476074
TI  - Plastid division.
AB  - BACKGROUND AND AIMS: Plastids undergo a process of binary fission in order to
      replicate. Plastid replication is required at two distinct stages of plant
      growth: during cell division to ensure correct plastid segregation, and during
      cell expansion and development to generate large populations of functional
      plastids, as in leaf mesophyll cells. This review considers some of the recent
      advances in the understanding of how plastids undergo binary fission, a process
      which uses several different proteins, both internal and external to the plastid,
      which have been derived from the original endosymbiont's genome as well as new
      proteins that have been recruited from the host genome. KEY POINTS: Several of
      the proteins currently used in this process in higher plants have homologues in
      modern-day bacteria. An alternative mode of replication by a budding-type
      mechanism also appears to be used in some circumstances. The review also
      highlights how most of our knowledge of plastid division is centred on the
      chloroplast developing in leaf mesophyll cells and a role for plastid division
      during the development of other plastid types is poorly understood. Whilst models
      for a protein-based mechanism have been devised, exactly how the division process
      is controlled at the plastid level and at the plastid population level is poorly
      understood.

PMID- 22476075
TI  - Molecular marker-based characterization in candidate plus trees of Pongamia
      pinnata, a potential biodiesel legume.
AB  - BACKGROUND AND AIMS: Pongamia pinnata, a legume tree, has many traditional uses
      and is a potential biodiesel plant. Despite its importance and the availability
      of appropriate molecular genetic tools, the full potential of Pongamia is yet to
      be realized. The objective of this study was to assess genetic diversity among 10
      systematically characterized candidate plus trees (CPTs) of P. pinnata from North
      Guwahati. METHODOLOGY: The application and informativeness of polymerase chain
      reaction-based molecular markers [random amplified polymorphic DNA (RAPD), inter
      simple sequence repeat (ISSR) and amplified fragment length polymorphism (AFLP)]
      to assess the genetic variability and relatedness among 10 CPTs of P. pinnata
      were investigated. PRINCIPAL RESULTS: Polymorphism rates of 10.48, 10.08 and 100
      % were achieved using 18 RAPD, 12 ISSR and 4 AFLP primer combinations,
      respectively. Polymorphic information content (PIC) varied in the range 0.33
      0.49, 0.18-0.49 and 0.26-0.34 for RAPD, ISSR and AFLP markers, respectively,
      whereas the corresponding average marker index (MI) values for the above markers
      were 7.48, 6.69 and 30.75. Based on Nei's gene diversity and Shannon's
      information index, inter-population diversity (h(sp)) was highest when compared
      with intra-population diversity (h(pop)) and the gene flow (N(m)) ranged from a
      moderate value of 0.607 to a high value of 6.287 for the three DNA markers.
      Clustering of individuals was not similar when RAPD- and ISSR-derived dendrogram
      analyses were compared with that of AFLP. The Mantel test cophenetic correlation
      coefficient was higher for AFLP (r = 0.98) than for ISSR (r = 0.73) and RAPD (r =
      0.84). Molecular markers discriminated the individuals efficiently and generated
      a high similarity in dendrogram topologies derived using unweighted pair-group
      arithmetic average, although some differences were observed. The three
      dimensional scaling by principal coordinate analysis supported the result of
      clustering. CONCLUSIONS: Comparing the results obtained with the three DNA
      markers, AFLP indicated higher efficiency for estimating the levels of genetic
      diversity and proved to be reliable for fingerprinting, mapping and diversity
      studies in Pongamia in view of their suitability for energy production purposes.

PMID- 22476076
TI  - Biogeography and divergence times of genus Macroptilium (Leguminosae).
AB  - BACKGROUND AND AIMS: Macroptilium is a herbaceous legume genus with 18 currently
      accepted species, seven of them with economic importance due to their use as
      forage, green fertilizer and in medicine. The genus is strictly American, with an
      unknown biogeographic history. The aim of this study was to infer a biogeographic
      pattern of Macroptilium and to estimate its divergence times, using sequences
      from the nuclear ribosomal DNA internal transcribed spacers. METHODOLOGY: To
      study the historical biogeography of Macroptilium, two approaches were used: area
      optimization on a previously obtained phylogeny and a dispersal-vicariance
      analysis. Divergence times were calculated by Bayesian methods. PRINCIPAL
      RESULTS: The analyses revealed that Macroptilium has its origin in the middle
      Pliocene, with an estimated age that ranges from 2.9 to 4 million years. The
      biogeographic analyses placed its origin in South America, specifically on the
      Chaquean sub-region, where most of the cladogenetic events of the genus took
      place. CONCLUSIONS: Macroptilium constitutes a further example of the geographic
      pattern displayed by numerous Neotropical taxa that moved north from South
      America to dominate the Central American lowlands after the land connection
      across the Isthmus of Panama was established.

PMID- 22476077
TI  - Population rules can apply to individual plants and affect their architecture: an
      evaluation on the cushion plant Mulinum spinosum (Apiaceae).
AB  - BACKGROUND AND AIMS: Plants are regarded as populations of modules such as axes
      and growth units (GUs, i.e. seasonally produced axis segments). Due to their
      dense arrays of GUs, cushion plants may resemble crowded plant populations in the
      way the number of components (GUs in plants, individuals in populations) relates
      to their individual sizes. METHODOLOGY: The morphological differentiation of GUs
      and its relationship with biomass accumulation and plant size were studied for
      the cushion subshrub Mulinum spinosum (Apiaceae), a widespread species in dry
      areas of Patagonia. In 2009, GUs were sampled from one-quarter of each of 24
      adult plants. Within- and between-plant variations in GU length, diameter, number
      of nodes and biomass were analysed and related to whole-plant size. PRINCIPAL
      RESULTS: Each year, an M. spinosum cushion develops flowering GUs and vegetative
      GUs. Flowering GUs are larger, twice as numerous and contain two to four times
      more dry mass (excluding reproductive structures) than vegetative GUs. The
      hemispherical area of the cushions was positively correlated with the biomass of
      last-year GUs. The biomass of flowering GUs was negatively correlated with the
      density of GUs. Mulinum spinosum plants exhibited a notable differentiation
      between flowering and vegetative GUs, but their axes, i.e. the sequences of GUs,
      were not differentiated throughout the plants. Flowering GUs comprised a major
      proportion of each plant's photosynthetic tissues. CONCLUSIONS: A decrease in the
      size of flowering GUs and in their number relative to the total number of GUs per
      plant, parallel to an increase in GU density, is predicted as M. spinosum plants
      age over years. The assimilative role of vegetative GUs is expected to increase
      in summer because of their less exposed position in the cushion. These GUs would
      therefore gain more from warm and dry conditions than flowering GUs.

PMID- 22476078
TI  - Bilirubin present in diverse angiosperms.
AB  - BACKGROUND AND AIMS: Bilirubin is an orange-yellow tetrapyrrole produced from the
      breakdown of heme by mammals and some other vertebrates. Plants, algae and
      cyanobacteria synthesize molecules similar to bilirubin, including the protein
      bound bilins and phytochromobilin which harvest or sense light. Recently, we
      discovered bilirubin in the arils of Strelitzia nicolai, the White Bird of
      Paradise Tree, which was the first example of this molecule in a higher plant.
      Subsequently, we identified bilirubin in both the arils and the flowers of
      Strelitzia reginae, the Bird of Paradise Flower. In the arils of both species,
      bilirubin is present as the primary pigment, and thus functions to produce
      colour. Previously, no tetrapyrroles were known to generate display colour in
      plants. We were therefore interested in determining whether bilirubin is broadly
      distributed in the plant kingdom and whether it contributes to colour in other
      species. METHODOLOGY: In this paper, we use HPLC/UV and HPLC/UV/electrospray
      ionization-tandem mass spectrometry (HPLC/UV/ESI-MS/MS) to search for bilirubin
      in 10 species across diverse angiosperm lineages. PRINCIPAL RESULTS: Bilirubin
      was present in eight species from the orders Zingiberales, Arecales and Myrtales,
      but only contributed to colour in species within the Strelitziaceae. CONCLUSIONS:
      The wide distribution of bilirubin in angiosperms indicates the need to re-assess
      some metabolic details of an important and universal biosynthetic pathway in
      plants, and further explore its evolutionary history and function. Although
      colour production was limited to the Strelitziaceae in this study, further
      sampling may indicate otherwise.

PMID- 22476079
TI  - The invasive 'mothcatcher' (Araujia sericifera Brot.; Asclepiadoideae) co-opts
      native honeybees as its primary pollinator in South Africa.
AB  - BACKGROUND AND AIMS: Successful invasive plants such as Araujia sericifera
      usually either are capable of automatic self-pollination or maintain pollinator
      services by having generalized pollination systems to make use of local
      pollinators in the invaded range. Alternatively, plants must co-opt new
      pollinators with similar morphology to native pollinators or reproduce asexually.
      We aimed to document the pollination biology of A. sericifera in South Africa.
      Given the success of this species as an invader, we predicted that sexual
      reproduction occurs either through self-pollination or because A. sericifera has
      successfully co-opted native insect pollinators. METHODOLOGY: We examined the
      pollination biology of the South American A. sericifera in South Africa. We
      documented the effective pollinators including a comparison of the efficacy of
      nocturnal versus diurnal pollinators as well as the breeding system and long-term
      natural levels of the pollination success of this species. PRINCIPAL RESULTS: We
      found that native honeybees (Apis mellifera) were the main pollinators of A.
      sericifera in South Africa. Visiting moths are unimportant pollinators despite
      being attracted by the pale colour and nocturnal scent of the flowers. Plants
      from the Grahamstown population were incapable of autonomous self-pollination but
      pollinator-mediated self-pollination does occur. However, the highest fruit
      initiation resulted from out-crossed pollination treatments. The high pollen
      transfer efficiency of this species was comparable to other hymenopteran
      pollinated exotic and native milkweeds, suggesting that A. sericifera maintains
      pollinator services at levels experienced by indigenous asclepiad species.
      CONCLUSIONS: Araujia sericifera reproduces successfully in South Africa due to a
      combined ability of this species to attract and exploit native honeybees as its
      pollinators and of individual plants to set fruit from pollinator-mediated self
      pollination.

PMID- 22476080
TI  - Mechanisms of plant adaptation/memory in rice seedlings under arsenic and heat
      stress: expression of heat-shock protein gene HSP70.
AB  - BACKGROUND AND AIMS: Plants can withstand many abiotic stresses. Stress
      adaptation through retention of imprints of previous stress exposure has also
      been described in plants. We have characterized the imprint or memory of adaptive
      stress responses of rice seedlings to arsenic (As) and heat stress. METHODOLOGY:
      Two-week-old rice seedlings (both with and without As) were given a 45  degrees C
      heat shock for 3 h. While under heat shock, the leafy portion of the seedlings
      was harvested at regular intervals. Subsequently, the seedlings were kept at room
      temperature for recovery and sampling continued over 3 h. Total RNA and protein
      were extracted from the leafy portion of the seedlings and complementary DNA
      (cDNA) was prepared from total RNA. The cDNA was used as a template for the
      polymerase chain reaction to identify the transcription level of HSP70. Protein
      extracted from the seedlings was western-blotted. HSP70 and actin (loading
      control) antibodies were used to recognize the proteins on the same blot.
      PRINCIPAL RESULTS: Our studies reveal that HSP70, a cellular chaperone gene, is
      over-expressed at the mRNA and protein levels when rice seedlings are exposed to
      As and heat. The effect is cumulative and increases with the duration of stress
      for 3 h. During 3 h recovery from heat stress at ambient temperatures for 3 h,
      the chaperone remains expressed at higher levels in plants pre-exposed to As.
      CONCLUSIONS: Our findings demonstrate a retention of the imprint of previous
      stress exposure, perhaps through sustained activation of the signalling pathways
      upstream of over-expression of HSP70. Furthermore, stress-induced HSP70
      expression was additive/cumulative for continued exposure to similar or different
      kinds of stress, indicating that a commonality of signal transduction networks is
      adopted when plants experience more than one stress.

PMID- 22476081
TI  - Theoretical study of triatomic silver (Ag3) and its ions with coupled-cluster
      methods and correlation-consistent basis sets.
AB  - Coupled-cluster calculations including non-iterative effects of triple
      excitations (CCSD(T)) have been made with correlation-consistent basis sets to
      study a range of properties of Ag3, Ag3(-), and Ag3(+). The methodology was
      tested on atomic and diatomic silver systems. The accuracy achieved for these
      systems suggests that predictive-quality results can be expected for the
      triatomic systems. Properties of the triatomic systems studied include structures
      and energies of ground and excited states (bent and linear geometries),
      dissociation energies, ionization energies, and vertical electron detachment
      energies. In the absence of experimental structural data, the present calculated
      data serve as reliable predictions. The calculated dissociation energies are near
      the middle of the experimental range (253 +/- 13 kJ mol(-1)). The calculated
      ionization energies clearly favor the lower of the two experimental measurements
      (i.e. 5.66 eV). Our calculated vertical electron detachment energies of linear
      Ag3(-) match the observed photoelectron data fairly well. Overall the higher
      levels of theory used in the present study achieve consistent accuracy for a
      range of properties. In contrast, some prior density-functional theory studies
      provide good results for certain properties, but are lacking in accuracy for
      others. Another feature of the present study is that it has not been necessary to
      empirically correct results on the triatomic systems because of known
      deficiencies in the results on atomic and diatomic systems. The majority of prior
      wave function-based studies cannot make this claim. 

PMID- 22476082
TI  - Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in
      C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese
      mice.
AB  - Although the flavonoid tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone) is known
      to possess beneficial health effects, the anti-diabetic effects and the mechanism
      of action have not been elucidated. Treatment with 100 MUM tangeretin
      significantly increased the uptake of 2-NBDG in C2C12 myotubes. We also found
      that AMPK and AS160 were markedly phosphorylated by tangeretin treatment. In
      addition, pretreatment with an AMPK inhibitor significantly abrogated tangeretin
      stimulated AS160 phosphorylation, glucose uptake, and Glut4 translocation from
      the cytosol to the plasma membrane. Furthermore, disruption of AMPK using siRNA
      transfection prevented the glucose uptake stimulated by tangeretin. We also
      examined the anti-diabetic properties of tangeretin in mice on HFD.
      Administration of HFD plus 200 mg/kg of tangeretin significantly altered weight
      gain, glucose tolerance, total cholesterol levels, and the secretion of
      adipocytokines, such as adiponectin, leptin, resistin, IL-6, and MCP-1. Moreover,
      AMPK was activated by 200 mg/kg of tangeretin in mouse muscle tissue, as expected
      from the cell system. These results suggest that tangeretin exerts anti-diabetic
      effects in both cell culture and mouse models, and these effects are necessary
      for activating AMPK.

PMID- 22476083
TI  - Gene array analysis of embryonic- versus adult-derived hypothalamic NPY
      expressing cell lines.
AB  - Few studies have utilized microarray analysis to understand the genome wide
      changes involved in the development of the hypothalamus despite its overall
      importance to basic physiology. Gene expression profiling of immortalized, clonal
      hypothalamic neurons, embryonic-derived mHypoE-46 and adult-derived mHypoA-2/12,
      reveals that the expression of 1225 probes was significantly changed between the
      two neuronal models. Further comparison of the gene expression profiles
      identified two categories of genes that were confirmed with qRT-PCR: (i) genes
      implicated in the Wnt signaling pathway; and (ii) transcription factors
      previously implicated in the development of the central nervous system. Yet,
      functional analysis of the two cell lines, including hormonal responses and
      secretion, indicate that they are comparable despite their developmental origin.
      This study provides a comprehensive analysis of embryonic- and adult-derived
      hypothalamic neuronal cell models that both express neuropeptide Y, and
      identifies novel genes as candidates for mediating the development of specific
      hypothalamic neurons.

PMID- 22476084
TI  - DDX5 is a multifunctional co-activator of steroid hormone receptors.
AB  - The vitamin D receptor (VDR), an evolutionarily conserved member of the nuclear
      receptor superfamily, links the metabolically activated vitamin D ligand,
      calcitriol, with its vitamin D-responsive target genes that are implicated in
      diverse physiological processes. By genome-wide protein-protein interaction
      screening of a keratinocyte cDNA library using VDR as bait, we found that the
      DEAD box RNA helicase p68, also referred to as DDX5, directly interacts with VDR.
      Domain analysis reveals that the ligand-binding domain of VDR is responsible for
      the binding, an interaction typical of NR co-activators. Interestingly, the VDR
      interacting domain of DDX5 lacks a LXXLL-motif and interaction analysis of helix
      12 VDR mutants E420K, E420Q and L417S, known to decrease binding affinity of
      LxxLL motif-containing co-activators showed no change in their interactions. As
      further support that this novel interactor might be involved in vitamin D
      stimulated transcriptional regulation, we demonstrate that VDR and DDX5 co
      localize within the nuclei of HaCaT keratinocytes and sub-cellular protein
      fractions. In vivo validation studies demonstrate, that overexpression of DDX5
      has the capability to enhance both, calcitriol-dependent transcription of known
      response genes and an extrachromosomal DR3-type reporter response. In agreement
      with this, shRNA based knock-down of DDX5 in keratinocytes compensates for this
      particular response. Finally, our findings reveal parallels between the VDR-DDX5
      interaction and the well-characterized interaction between DDX5 and human
      estrogen receptor alpha and the androgen receptor, thus underscoring the
      physiological significance of the novel protein-protein interaction.

PMID- 22476085
TI  - Transition metal ion-assisted photochemical generation of alkyl halides and
      hydrocarbons from carboxylic acids.
AB  - Near-UV photolysis of aqueous solutions of propionic acid and aqueous Fe(3+) in
      the absence of oxygen generates a mixture of hydrocarbons (ethane, ethylene and
      butane), carbon dioxide, and Fe(2+). The reaction becomes mildly catalytic (about
      five turnovers) in the presence of oxygen which converts a portion of alkyl
      radicals to oxidizing intermediates that reoxidize Fe(2+). The photochemistry in
      the presence of halide ions (X(-) = Cl(-), Br(-)) generates ethyl halides via
      halogen atom abstraction from FeX(n)(3-n) by ethyl radicals. Near-quantitative
      yields of C(2)H(5)X are obtained at >=0.05 M X(-). Competition experiments with
      Co(NH(3))(5)Br(2+) provided kinetic data for the reaction of ethyl radicals with
      FeCl(2+) (k = (4.0 +/- 0.5) * 10(6) M(-1) s(-1)) and with FeBr(2+) (k = (3.0 +/-
      0.5) * 10(7) M(-1) s(-1)). Photochemical decarboxylation of propionic acid in the
      presence of Cu(2+) generates ethylene and Cu(+). Longer-chain acids also yield
      alpha olefins as exclusive products. These reactions become catalytic under
      constant purge with oxygen which plays a dual role. It reoxidizes Cu(+) to
      Cu(2+), and removes gaseous olefins to prevent accumulation of Cu(+)(olefin)
      complexes and depletion of Cu(2+). The results underscore the profound effect
      that the choice of metal ions, the medium, and reaction conditions exert on the
      photochemistry of carboxylic acids.

PMID- 22476087
TI  - Implementation challenges and functional outcome predictors for elder community
      based disability prevention programs.
AB  - BACKGROUND AND PURPOSE: Strategies to foster elder well-being and reduce long
      term care costs include efficacious community disability prevention programs.
      However, it is often difficult to replicate clinical trials into real-world
      practice settings. We (a) compared replication and clinical trial functional
      changes, (b) compared replication and clinical trial program structures and
      processes of care, and, additionally, (c) examined how replication client and
      site features are associated with function. METHODS: We used secondary
      longitudinal data on 719 elder clients, and primary data through interviews with
      nurses, social workers, and site managers for the replication, and compared this
      to original trial data. We analyzed associations between baseline self-efficacy
      and functional outcomes and between site features and functional outcomes using
      multivariate and logistic models for the replication. RESULTS: Replication
      functional outcome changes were lower and structures and processes were less
      intense than in the original clinical trial. Baseline client higher self-efficacy
      positively influenced 12-month function, and smaller sites and urban sites had
      better functional outcomes than larger sites and rural sites for the replication.
      DISCUSSION AND CONCLUSION: Exploring systemic strategies for using available
      resources to improve research translation is essential. In addition,
      practitioners need to focus on client self-efficacy enhancement techniques, which
      may be more important in replication studies to improve function.

PMID- 22476088
TI  - A simple model to estimate deposition based on a statistical reassessment of
      global fallout data.
AB  - Atmospheric testing of nuclear weapons began in 1945 and largely ceased in 1963.
      Monitoring of the resulting global fallout was carried out globally by the
      Environmental Measurements Laboratory and the UK Atomic Energy Research
      Establishment as well as at national level by some countries. A correlation was
      identified between fallout deposition and precipitation and an uneven
      distribution with latitude. In this study, the available data from 1954 to 1976
      for (90)Sr and (137)Cs were reanalysed using analysis of covariance (ANCOVA) and
      logarithmically transformed values of the monthly deposition density as the
      response variable. Generalized additive models (GAM) were used to explore the
      relationship of different variables to the response variable and quantify the
      explanatory power that could be achieved. The explanatory variables which
      consistently explained most of the variability were precipitation at each site,
      latitude and change with time and a simple linear model was produced with similar
      explanatory power as the GAM. The estimates improved as the temporal resolution
      of the precipitation data increased. A good log-log fit could be obtained if a
      bias of about 1-6 mm precipitation per month was added, this could be interpreted
      as dry deposition which is not otherwise accounted for in the model. The
      deposition rate could then be explained as a simple non-linear power function of
      the precipitation rate (r(0.2-0.6) depending on latitude band). A similar non
      linear power function relationship has been the outcome of some studies linking
      wash-out and rain-out coefficients with rain intensity. Our results showed that
      the precipitation rate was an important parameter, not just the total amount. The
      simple model presented here allows the recreation of the deposition history at a
      site, allowing comparison with time series of activity concentrations for
      different environmental compartments, which is important for model validation.

PMID- 22476090
TI  - New bioactive motifs and their use in functionalized self-assembling peptides for
      NSC differentiation and neural tissue engineering.
AB  - Developing functionalized biomaterials for enhancing transplanted cell
      engraftment in vivo and stimulating the regeneration of injured tissues requires
      a multi-disciplinary approach customized for the tissue to be regenerated. In
      particular, nervous tissue engineering may take a great advantage from the
      discovery of novel functional motifs fostering transplanted stem cell engraftment
      and nervous fiber regeneration. Using phage display technology we have discovered
      new peptide sequences that bind to murine neural stem cell (NSC)-derived neural
      precursor cells (NPCs), and promote their viability and differentiation in vitro
      when linked to LDLK12 self-assembling peptide (SAPeptide). We characterized the
      newly functionalized LDLK12 SAPeptides via atomic force microscopy, circular
      dichroism and rheology, obtaining nanostructured hydrogels that support human and
      murine NSC proliferation and differentiation in vitro. One functionalized
      SAPeptide (Ac-FAQ), showing the highest stem cell viability and neural
      differentiation in vitro, was finally tested in acute contusive spinal cord
      injury in rats, where it fostered nervous tissue regrowth and improved locomotor
      recovery. Interestingly, animals treated with the non-functionalized LDLK12 had
      an axon sprouting/regeneration intermediate between Ac-FAQ-treated animals and
      controls. These results suggest that hydrogels functionalized with phage-derived
      peptides may constitute promising biomimetic scaffolds for in vitro NSC
      differentiation, as well as regenerative therapy of the injured nervous system.
      Moreover, this multi-disciplinary approach can be used to customize SAPeptides
      for other specific tissue engineering applications.

PMID- 22476091
TI  - A charge transfer assisted fluorescent probe for selective detection of hydrogen
      peroxide among different reactive oxygen species.
AB  - A charge transfer assisted fluorescent probe is synthesized which undergoes a
      change in fluorescence emission at two different wavelengths in the presence of
      hydrogen peroxide.

PMID- 22476092
TI  - The investigation of kinetic and isotherm of fluoride adsorption onto
      functionalize pumice stone.
AB  - In this research work, pumice that is functionalized by the cationic surfactant,
      hexadecyltrimethyl ammonium (HDTMA), is used as an adsorbent for the removal of
      fluoride from drinking water. This work was carried out in two parts. The effects
      of HDTMA loading, pH (3-10), reaction time (5-60 min) and the adsorbent dosage
      (0.15-2.5 g L(-1)) were investigated on the removal of fluoride as a target
      contaminate from water through the design of different experimental sets in the
      first part. The results from this first part revealed that surfactant-modified
      pumice (SMP) exhibited the best performance at dose 0.5 g L(-1), pH 6, and it
      adsorbs over 96% of fluoride from a solution containing 10 mg L(-1) fluoride
      after 30 min of mixing time. The four linear forms of the Langmuir, Freundlich,
      Temkin and Dubinin-Radushkevich isotherms model were applied to determine the
      best fit of equilibrium expressions. Apart from the regression coefficient
      (R(2)), four error functions were used to validate the isotherm and kinetics
      data. The experimental adsorption isotherm complies with Langmuir equation model
      type 1. The maximum amount of adsorption (Q(max)) was 41 mg g(-1). The kinetic
      studies indicated that the adsorption of fluoride best fitted with the pseudo
      second-order kinetic type 1. Thermodynamic parameters evaluation of fluoride
      adsorption on SMP showed that the adsorption process under the selected
      conditions was spontaneous and endothermic. The suitability of SMP in
      defluoridation at field condition was investigated with natural groundwater
      samples collected from a nearby fluoride endemic area in the second part of this
      study. Based on this study's results, SMP was shown to be an affordable and a
      promising option for the removal of fluoride in drinking water.

PMID- 22476093
TI  - Removal of emerging contaminants from municipal wastewater with an integrated
      membrane system, MBR-RO.
AB  - The presence of emerging contaminants in the aquatic environment and their
      potential effects on living organisms has become an issue of growing concern.
      Among emerging contaminants, pharmaceuticals may enter the aquatic environment
      due to their high consumption and their incomplete removal in conventional
      municipal wastewater treatment plants (WWTPs). The main goal of this study was
      the assessment of the removal efficiency of pharmaceuticals found in municipal
      wastewater of a coastal WWTP (Castell-Platja d'Aro, Spain) using an integrated
      pilot scale membrane system (MBR-RO). Twenty multiple-class pharmaceuticals
      (including psychiatric drugs, macrolide antibiotics, beta-blockers, sulfonamide
      and fluoroquinolone antibiotics, histamine H2 receptor antagonists, anti
      inflammatories, nitroimidazole, beta-agonist and antiplatelet agent) were
      measured in real influent with the lowest average concentration for psychiatric
      drugs (0.017 MUg L(-1)) to the highest for macrolide antibiotics (2.02 MUg L(
      1)). Although some contaminants were in relatively high concentrations (even up
      to 2.90 MUg L(-1) in the case of ofloxacin). The combination of MBR and RO
      treatment showed excellent overall removal of target emerging contaminants with
      removal rates above 99% for all of them. For some compounds (metronidazole,
      hydrocodone, codein, ranitidine) MBR provided high removal efficiency (up to
      95%). Additionally RO membrane showed removal rates always higher than 99%.

PMID- 22476094
TI  - Thiol compounds induction kinetics in marine phytoplankton during and after
      mercury exposure.
AB  - We investigated the kinetics of Hg(II) and MeHg accumulation and the synthesis of
      phytochelatins (PCs), cysteine (Cys), glutathione (GSH), and gamma
      glutamylcysteine (gamma-EC) in a marine diatom Thalassiosira weissflogii during a
      3-h (short-term) and a 96-h (long-term) exposure period, and during a subsequent
      96-h recovery period. MeHg induced the synthesis of a significant level of GSH,
      but it was Hg(II) that gave rise to significant levels of other non-protein thiol
      compounds. The thiol compounds Cys, gamma-EC, and PC(2-3) were induced in T.
      weissflogii within the first 30 min of exposure, followed by PC(4), but the
      concentrations of all six compounds returned to the control levels after the 96-h
      recovery period. The kinetics of these non-protein thiol compounds pointed to a
      rapid cellular response to environmental mercury pollution. After a first
      decrease, the molar ratio of PC-SH (sulfhydryl in PCs) to intracellular Hg
      increased slightly which demonstrated the role of PCs in Hg(II) detoxification.
      However, PC-SH was bound with Hg(II) at a stoichiometric ratio of 0.1-0.3,
      indicating the involvement of other detoxification mechanisms. Elucidating the
      effects of mercury on intracellular non-protein thiol pools may help us better
      understand the metal detoxification in phytoplankton.

PMID- 22476095
TI  - Effects of humic acid and suspended soils on adsorption and photo-degradation of
      microcystin-LR onto samples from Taiwan reservoirs and rivers.
AB  - This article covers the adsorption capacity of microcystin-LR (MC-LR) onto
      natural organic matter (NOM) or suspended solids of water samples from reservoirs
      (Emerald and Jade reservoirs) and rivers (Dongshan, Erhjen and Wukai rivers) in
      Taiwan to determine the fate, transport behavior and photo-degradation of
      microcystins in natural water systems. Langmuir adsorption and photo-degradation
      studies were carried out and the capability of samples for MC-LR adsorption was
      confirmed. Among these, samples collected from reservoir showed enhanced MC-LR
      adsorption than that of river samples and the greater adsorption behavior was
      always favored by larger content of organic matter and suspended particles in the
      system. It is obvious from the experimental results that the adsorption of MC-LR
      was influenced by suspended particles (turbidity), humic acid (HA), organic
      matter content and other pollutants. The effective photo-degradation of MC-LR was
      achieved using higher energy, lower wavelength (254 nm) UV light within 60 min.
      The presence of humic acid and turbidity affected the photo-degradation process.
      These data provide important information that may be applied to management
      strategies for improvement of water quality in reservoirs and rivers and other
      water bodies in Taiwan.

PMID- 22476089
TI  - The young brain and concussion: imaging as a biomarker for diagnosis and
      prognosis.
AB  - Concussion (mild traumatic brain injury (mTBI)) is a significant pediatric public
      health concern. Despite increased awareness, a comprehensive understanding of the
      acute and chronic effects of concussion on central nervous system structure and
      function remains incomplete. Here we review the definition, epidemiology, and
      sequelae of concussion within the developing brain, during childhood and
      adolescence, with current data derived from studies of pathophysiology and
      neuroimaging. These findings may contribute to a better understanding of the
      neurological consequences of traumatic brain injuries, which in turn, may lead to
      the development of brain biomarkers to improve identification, management and
      prognosis of pediatric patients suffering from concussion.

PMID- 22476096
TI  - Bio-filler from waste shellfish shell: preparation, characterization, and its
      effect on the mechanical properties on polypropylene composites.
AB  - Waste shellfish shell stacking with a significant odor and toxicity which are
      hazardous to human constitutes a serious environmental hazard. For utilization of
      waste shellfish shell resource, granule of shellfish shell (SS) was prepared from
      waste shellfish shell by removing cuticle, crushing, grinding and shearing
      emulsification and was introduced as a filler to reinforce polypropylene (PP).
      The mechanical behavior of PP/SS composite shows a higher yield strain, yield
      strength, tensile strength and elongation at break than traditional commercial
      calcium carbonate (CC) filled PP. Yield strength of PP/SS composite with 2% SS is
      improved by 11.1% due to the formation of beta-crystalline PP phase. Using waste
      SS for producing bio-filler for filling PP is an effective and prospective
      measure to deal with waste SS, which is valuable for industrial production and
      practical application as fillers for reinforcing polymers.

PMID- 22476098
TI  - Activation of autophagy induces retinal ganglion cell death in a chronic
      hypertensive glaucoma model.
AB  - Autophagy is reported to have important roles in relation to regulated cell death
      pathways and neurodegeneration. This study used chronic hypertensive glaucoma rat
      model to investigate whether the autophagy pathway has a role in the apoptosis of
      retinal ganglion cells (RGCs) after chronic intraocular pressure (IOP) elevation.
      Under electron microscopy, autophagosomes were markedly accumulated in the
      dendrites and cytoplasm of RGCs after IOP elevation. Western blot analysis showed
      that LC3-II/LC3-I and beclin-1 were upregulated throughout the 8-weeks period
      after IOP elevation. The pattern of LC3 immunostaining showed autophagy
      activation in the cytoplasm of RGCs to increase and peak at 4 weeks after IOP
      elevation. Most of these LC3B-positive RGCs underwent apoptosis by terminal
      deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling, and
      inhibition of autophagy with 3-methyladenine decreased RGC apoptosis. The
      activated pattern shows that autophagy is initially activated in the dendrites of
      the RGCs, but, thereafter autophagy is mainly activated in the cytoplasm of RGCs.
      This may show that autophagy is differently regulated in different compartments
      of the neuron. This present study showed that autophgy is activated in RGCs and
      has a role in autophagic cell death after chronic IOP elevation.

PMID- 22476097
TI  - Decreased expression of the augmenter of liver regeneration results in increased
      apoptosis and oxidative damage in human-derived glioma cells.
AB  - The mammalian growth factor erv1-like (GFER) gene encodes a sulfhydryl oxidase
      enzyme, named Augmenter of Liver Regeneration (ALR). Recently it has been
      demonstrated that ALR supports cell proliferation acting as an anti-apoptotic
      factor. This effect is determined by ALR ability to support the anti-apoptotic
      gene expression and to preserve cellular normoxic conditions. We recently
      demonstrated that the addition of recombinant ALR (rALR) in the culture medium of
      H(2)O(2)-treated neuroblastoma cells reduces the lethal effects induced by the
      hydrogen peroxide. Similar data have been reported in the regenerating liver
      tissue from partially hepatectomized rats treated with rALR. The purpose of the
      present study was to evaluate the effect of the GFER inhibition, via the
      degradation of the complementary mRNA by the specific siRNA, on the behaviour of
      the apoptosis (apoptotic gene and caspase expression and apoptotic cell number)
      and of the oxidative stress-induced parameters (reactive oxygen species (ROS),
      clusterin expression and mitochondrial integrity) in T98G glioma cells. The
      results revealed a reduction of (i) ALR, (ii) clusterin and (iii) bcl-2 and an
      increase of (iv) caspase-9, activated caspase-3, ROS, apoptotic cell number and
      mitochondrial degeneration. These data confirm the anti-apoptotic role of ALR and
      its anti-oxidative properties, and shed some light on the molecular pathways
      through which ALR modulates its biological effects.

PMID- 22476099
TI  - PP2A inactivation is a crucial step in triggering apoptin-induced tumor-selective
      cell killing.
AB  - Apoptin (apoptosis-inducing protein) harbors tumor-selective characteristics
      making it a potential safe and effective anticancer agent. Apoptin becomes
      phosphorylated and induces apoptosis in a large panel of human tumor but not
      normal cells. Here, we used an in vitro oncogenic transformation assay to explore
      minimal cellular factors required for the activation of apoptin. Flag-apoptin was
      introduced into normal fibroblasts together with the transforming SV40 large T
      antigen (SV40 LT) and SV40 small t antigen (SV40 ST) antigens. We found that
      nuclear expression of SV40 ST in normal cells was sufficient to induce
      phosphorylation of apoptin. Mutational analysis showed that mutations disrupting
      the binding of ST to protein phosphatase 2A (PP2A) counteracted this effect.
      Knockdown of the ST-interacting PP2A-B56gamma subunit in normal fibroblasts
      mimicked the effect of nuclear ST expression, resulting in induction of apoptin
      phosphorylation. The same effect was observed upon downregulation of the PP2A
      B56delta subunit, which is targeted by protein kinase A (PKA). Apoptin interacts
      with the PKA-associating protein BCA3/AKIP1, and inhibition of PKA in tumor cells
      by treatment with H89 increased the phosphorylation of apoptin, whereas the PKA
      activator cAMP partially reduced it. We infer that inactivation of PP2A, in
      particular, of the B56gamma and B56delta subunits is a crucial step in triggering
      apoptin-induced tumor-selective cell death.

PMID- 22476100
TI  - Inhibition of ER stress-mediated apoptosis in macrophages by nuclear-cytoplasmic
      relocalization of eEF1A by the HIV-1 Nef protein.
AB  - HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We
      assessed the role of the Nef/eEF1A (eukaryotic translation elongation factor 1
      alpha) complex in nucleocytoplasmic shuttling in primary human macrophages.
      Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway
      suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t, occurs in
      Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA
      in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A
      complexes prevented stress-induced apoptosis of MDMs treated with brefeldin-A.
      Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from
      enhanced nucleocytoplasmic transport of eEF1A with decreased release of
      mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c,
      ultimately leading to an inhibition of caspase activation. Our results indicate
      that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs,
      enhances resistance to stress-induced apoptosis in primary human macrophages.

PMID- 22476101
TI  - Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan
      horse approach to eradicate multidrug-resistant cancers.
AB  - Multidrug resistance (MDR) remains a primary hindrance to curative cancer
      therapy. Thus, introduction of novel strategies to overcome MDR is of paramount
      therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an
      established mechanism of drug resistance. Here, we show that MDR cells display a
      marked increase in lysosome number. We further demonstrate that
      imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic
      compartmentalization in lysosomes because of their hydrophobic weak base nature.
      We hence developed a novel photoactivation-based pharmacological Trojan horse
      approach to target and eradicate MDR cancer cells based on photo-rupture of IA
      loaded lysosomes and tumor cell lysis via formation of reactive oxygen species.
      Illumination of IA-loaded cells resulted in lysosomal photodestruction and
      restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR
      cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1
      resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring
      parental cell sensitivity. Finally, in vivo application of this photodynamic
      therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in
      the chorioallantoic membrane model revealed selective destruction of tumors and
      their associated vasculature. These findings identify lysosomal sequestration of
      IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor
      cells via lysosomal photodestruction.

PMID- 22476102
TI  - Human neuroblastoma cells with acquired resistance to the p53 activator RITA
      retain functional p53 and sensitivity to other p53 activating agents.
AB  - Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double
      minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency
      (13/20) and multi-drug resistance. Here, we show that the same cells respond very
      differently when adapted to RITA, a drug that, like nutlin-3, also disrupts the
      p53/Mdm2 interaction. All of the 11 UKF-NB-3 sub-lines adapted to RITA that we
      established retained functional wild-type p53 although RITA induced a substantial
      p53 response. Moreover, all RITA-adapted cell lines remained sensitive to nutlin
      3, whereas only five out of 10 nutlin-3-adapted cell lines retained their
      sensitivity to RITA. In addition, repeated adaptation of the RITA-adapted sub
      line UKF-NB-3(r)RITA(10 MUM) to nutlin-3 resulted in p53 mutations. The RITA
      adapted UKF-NB-3 sub-lines displayed no or less pronounced resistance to
      vincristine, cisplatin, and irradiation than nutlin-3-adapted UKF-NB-3 sub-lines.
      Furthermore, adaptation to RITA was associated with fewer changes at the
      expression level of antiapoptotic factors than observed with adaptation to nutlin
      3. Transcriptomic analyses indicated the RITA-adapted sub-lines to be more
      similar at the gene expression level to the parental UKF-NB-3 cells than nutlin-3
      adapted UKF-NB-3 sub-lines, which correlates with the observed chemotherapy and
      irradiation sensitivity phenotypes. In conclusion, RITA-adapted cells retain
      functional p53, remain sensitive to nutlin-3, and display a less pronounced
      resistance phenotype than nutlin-3-adapted cells.

PMID- 22476103
TI  - Genetics of adrenocortical disease:  an update.
AB  - PURPOSE OF REVIEW: Disease states characterized by abnormal cellular function or
      proliferation frequently reflect aberrant genetic information. By revealing
      disease-specific DNA mutations, we gain insight into normal physiology,
      pathophysiology, potential therapeutic targets and are better equipped to
      evaluate an individual's disease risks. This review examines recent advances in
      our understanding of the genetic basis of adrenal cortical disease. RECENT
      FINDINGS: Important advances made in the past year have included identification
      of KCNJ5 potassium channel mutations in the pathogenesis of both aldosterone
      producing adenomas and familial hyperaldosteronism type III; characterization of
      phosphodiesterase 11A as a modifier of phenotype in Carney complex caused by
      protein kinase, cAMP-dependent, regulatory subunit, type-I mutations; the finding
      of 11beta-hydroxysteroid dehydrogenase type I mutations as a novel mechanism for
      cortisone reductase deficiency; and demonstration of potential mortality benefit
      in pursuing comprehensive presymptomatic screening for patients with Li-Fraumeni
      syndrome, including possible reduction in risks associated with adrenocortical
      carcinoma. SUMMARY: This research review provides a framework for the
      endocrinologist to maintain an up-to-date understanding of adrenal cortical
      disease genetics.

PMID- 22476104
TI  - Management of boys and men with disorders of sex development.
AB  - PURPOSE OF REVIEW: This review of disorders of sex development (DSDs) in boys and
      men will outline the conditions that may lead to this phenotype, present some
      guidance on how to evaluate and investigate affected cases and then review the
      medical and surgical management and subsequent outcome. RECENT FINDINGS: DSDs are
      a wide range of relatively rare conditions which need multidisciplinary input.
      The underlying cause is clearer in girls with DSDs, but the actual diagnosis
      remains unclear in the majority of boys with DSDs. SUMMARY: There is a need to
      improve the diagnostic yield and develop standardized methods for assessing,
      describing and investigating DSDs as well as for reporting outcome. This will
      lead to improved clinical management and genetic counselling.

PMID- 22476105
TI  - Quantification of proteome dynamics in Corynebacterium glutamicum by (15)N
      labeling and selected reaction monitoring.
AB  - Selected reaction monitoring allows quantitative measurements of proteins over
      several orders of magnitude in complex biological samples. Here we present a
      targeted approach for quantification of 19 enzymes from Corynebacterium
      glutamicum applying isotope dilution mass spectrometry coupled to high
      performance liquid chromatography (IDMS-LC-MS/MS). Investigations of protein
      dynamics upon growth on acetate and glucose as sole carbon source shows highly
      stable peptide amounts for enzymes of the central carbon metabolism during the
      transition phase and after substrate depletion. However significant adaptations
      of protein amounts are observed between both growth conditions well agreeing with
      known changes in metabolic fluxes. Time-resolved measurements of protein
      expression after metabolic switch from glycolytic to gluconeogenetic conditions
      reveal fast responses in protein synthesis rates for glyoxylate shunt enzymes.

PMID- 22476106
TI  - Selective sweeps in growing microbial colonies.
AB  - Evolutionary experiments with microbes are a powerful tool to study mutations and
      natural selection. These experiments, however, are often limited to the well
      mixed environments of a test tube or a chemostat. Since spatial organization can
      significantly affect evolutionary dynamics, the need is growing for evolutionary
      experiments in spatially structured environments. The surface of a Petri dish
      provides such an environment, but a more detailed understanding of microbial
      growth on Petri dishes is necessary to interpret such experiments. We formulate a
      simple deterministic reaction-diffusion model, which successfully predicts the
      spatial patterns created by two competing species during colony expansion. We
      also derive the shape of these patterns analytically without relying on
      microscopic details of the model. In particular, we find that the relative
      fitness of two microbial strains can be estimated from the logarithmic spirals
      created by selective sweeps. The theory is tested with strains of the budding
      yeast Saccharomyces cerevisiae for spatial competitions with different initial
      conditions and for a range of relative fitnesses. The reaction-diffusion model
      also connects the microscopic parameters like growth rates and diffusion
      constants with macroscopic spatial patterns and predicts the relationship between
      fitness in liquid cultures and on Petri dishes, which we confirmed
      experimentally. Spatial sector patterns therefore provide an alternative fitness
      assay to the commonly used liquid culture fitness assays.

PMID- 22476107
TI  - Can medication management coordinators help improve continuity of care after
      psychiatric hospitalization?
AB  - OBJECTIVE: This demonstration project examined whether medication management
      coordinators enhanced continuity of care from inpatient facilities to an
      outpatient public mental health clinic. METHODS: From 2004 to 2008, patients
      (N=325) hospitalized with schizophrenia or schizoaffective or bipolar disorder
      enrolled in a medication management program before discharge or at their first
      clinic appointment. Medication management coordinators supplemented existing
      clinic practices by identifying recently hospitalized patients, providing
      inpatient and outpatient prescribing clinicians with patients' complete
      medication history, meeting with patients for six months postdischarge to assess
      clinical status and provide medication education, and advocating guideline
      concordant prescribing. Recently discharged patients (N=345) assigned to a
      different outpatient clinic within the same agency served as the comparison
      group. Intent-to-treat, repeated-measures analyses for mixed models compared the
      groups' number of hospital admissions, hospital days, and medication appointments
      kept and use of nurse or case manager contact hours and emergency or crisis
      services during the 12 months before enrollment, the six-month intervention, and
      the six-month follow-up period. RESULTS: After discharge, individuals enrolled in
      medication management were more likely than comparison patients to attend
      outpatient appointments, and they had more medication visits and nurse or case
      manager treatment hours than the comparison group. Use of hospital and crisis or
      emergency services by all patients decreased. Almost one-third of patients never
      attended an outpatient appointment after hospital discharge. CONCLUSIONS:
      Although this program succeeded in improving continuity of care, additional
      interventions may be required to reduce rehospitalization and crisis care.

PMID- 22476110
TI  - Welcome to AoB PLANTS: the open access journal for all plant biologists.
AB  - The Chief Editor of AoB PLANTS highlights some of the key features of this new
      online, open access journal for plant biologist and sets out some of the reasons
      for starting.

PMID- 22476108
TI  - A behavioral mechanism underlying ecological divergence in the malaria mosquito
      Anopheles gambiae.
AB  - Disruptive selection mediated by predation on aquatic immature stages has been
      proposed as a major force driving ecological divergence and fostering speciation
      between the M and S molecular forms of the African malaria mosquito, Anopheles
      gambiae. In the dry savannahs of West Africa where both molecular forms co-occur,
      the S form thrives in temporary pools filled with rainwater, whereas the M form
      preferentially breeds in permanent freshwater habitats where predator pressure is
      higher. Here, we explored the proximal mechanisms by which predation may
      contribute to habitat segregation between molecular forms using progeny of female
      mosquitoes captured in Burkina Faso. We show that the S form suffers higher
      predation rates than the M form when simultaneously exposed to the widespread
      predator, Anisops jaczewskii in an experimental arena. Furthermore, behavioral
      plasticity induced by exposure to the predator was observed in the M form, but
      not in the S form, and may partially explain its habitat use and ecological
      divergence from the S form. We discuss the role of adaptive phenotypic plasticity
      in allowing successful colonization of a new ecological niche by the M form and
      highlight further research areas that need to be addressed for a better
      understanding of the ultimate mechanisms underlying ecological speciation in this
      pest of major medical importance.

PMID- 22476111
TI  - AoB PLANTS: origins and features.
AB  - INTRODUCTION: AoB PLANTS is a peer reviewed, Open Access (OA) journal owned and
      run by plant biologists and published by Oxford University Press. The journal
      publishes research papers, reviews and opinion papers on all aspects of land
      based plant biology. They are made available rapidly online and can be accessed
      without the need for subscriptions or payment. BACKGROUND: Several difficulties
      in conventional publishing of peer-reviewed manuscripts encouraged AoB PLANTS to
      adopt OA. Open Access helps sidestep library budgets which are struggling to
      purchase the increasing numbers of journals. Open Access makes research freely
      available both to the academic community and beyond while publishing online only
      eliminates the need to reject good manuscripts simply to control the size of the
      printed journal. Finally, the journal chose to go OA to ensure the widest
      possible international readership for the growing amount of high-quality plant
      science research being carried out worldwide in response to problems such as
      climate change and food shortages. Responses to a wide-ranging online
      questionnaire indicated strong international support for a journal such as AoB
      PLANTS. PRINCIPAL FEATURES: AoB PLANTS strives for fair and rapid peer review
      followed by fast publication of accepted papers. For an initial period, there
      will be no OA fees, and fees will remain modest once introduced. AoB PLANTS
      adopts double-blind peer review using published criteria for acceptability as a
      basis for decision-making. Accepted papers are published shortly after acceptance
      together with referees' analyses using Stanford University Libraries High Wire
      Press H2O platform. Authors retain ownership of the copyright in their papers.

PMID- 22476112
TI  - The association between body mass index class, sickness absence, and
      presenteeism.
AB  - OBJECTIVE: To examine the relationship between body mass index class,
      presenteeism, and prospective registered sickness absence. METHODS: Data were
      collected from 2983 Belgian workers. Presenteeism was assessed by a single
      question, evaluating the frequency of being at work, despite illness, during the
      preceding year. Sickness absence data were registered during 12 months' follow
      up. Multiple logistic regression analysis was conducted. RESULTS: Body mass index
      class was positively and significantly associated with presenteeism (at least two
      occasions of working despite illness) in the male employees and was a significant
      predictor of high sickness absence (at least 10 sick leave days) in the female
      population. A final multivariate model demonstrated that these relations were
      only partly mediated by self-rated health. CONCLUSION: The results of this study
      suggest a gender difference concerning absenteeism and presenteeism in overweight
      and obese employees.

PMID- 22476114
TI  - Columnar order in jammed LiFePO4 cathodes: ion transport catastrophe and its
      mitigation.
AB  - The high-rate, high-capacity potential of LiFePO4-based lithium-ion battery
      cathodes has motivated numerous experimental and theoretical studies aiming to
      realize such performance through nano-sizing, tailoring of particle shape through
      synthesis conditions, and doping. Here, a granular mechanics study of
      microstructures formed by dense jammed packings of experimentally and
      theoretically inspired LiFePO4 particle shapes is presented. A strong dependence
      of the resultant packing structures on particle shapes is observed, in which
      columnar structures aligned with the [010] direction inhibit diffusion along
      [010] in anisotropic LiFePO4. Transport limitations are induced by [010] columnar
      order and lead to catastrophic performance degradation in anisotropic LiFePO4
      electrodes. Further, judicious mixing of nanoplatelets with additive
      nanoparticles can frustrate columnar ordering and thereby enhance the rate
      capability of LiFePO4 electrodes by nearly an order of magnitude. 

PMID- 22476113
TI  - Application of the RE-AIM framework to evaluate the impact of a worksite-based
      financial incentive intervention for smoking cessation.
AB  - OBJECTIVE: To apply the RE-AIM framework to examine factors that may have
      influenced the impact of a financial incentive smoking cessation intervention
      delivered at General Electric (GE) worksites. METHODS: Intervention reach and
      efficacy were examined alone and in combination across worksites. Telephone
      interviews were conducted with worksite staff to explore organizational-level
      factors that may have influenced program adoption, implementation, and
      maintenance. Focus groups were conducted with employees to explore barriers and
      facilitators to program participation. RESULTS: Intervention impact varied
      considerably across GE business industries when reach and efficacy both were
      examined instead of efficacy alone. Barriers that may have hindered program
      success include time constraints, competing priorities, work stress, and the lack
      of public visibility. CONCLUSION: Employers considering financial incentive
      interventions for smoking cessation should examine how organizational context and
      real-world constraints may influence differential impact across sites.

PMID- 22476115
TI  - Electrochemical oxidation of amides of type Ph2CHCONHAr.
AB  - Anodic oxidation of N-aryl-2,2-diphenylacetamides in acetonitrile undergoes three
      types of bond-cleavage, one between the benzylic carbon and the carbonyl group,
      the second between a carbonyl and 'N', and the third between the 'N' atom and
      aryl group. The selectivity of the cleavage and nature of emerged products is
      highly dependent on the nature of substituent attached to the aryl group. For
      example, electron-withdrawing groups direct the benzyl-carbonyl bond-breaking
      whereas electron-donating substituents favor the N-aryl bond cleavage. The type
      of products obtained involve benzophenone, 2,2-diphenylacetamide, N
      (diphenylmethylene)acetamide, N-(diphenylmethyl)acetamide, alpha-lactam (1-acetyl
      3,3-diphenylaziridin-2-one, as a 1 : 1 complex with 2,4-dinitroaniline) and
      aniline derivatives.

PMID- 22476116
TI  - Suicide of first-generation immigrants in Australia, 1974-2006.
AB  - PURPOSE: This study analysed suicide rates among first-generation immigrants in
      Australia from 1974 to 2006, and compared their suicide risks against the
      Australian-born population. It also examined the associations between the suicide
      rates of immigrants from 23 selected countries of birth during 2001-2006, and in
      their home countries. METHOD: Age-standardised suicide rates (15+ years) and rate
      ratios, with a 95 % confidence interval, during 1974-2006 were calculated for
      country of birth (COB) groups. Spearman's rank correlation coefficient was
      calculated between COB-specific immigrant suicide rates during 2001-2006 in
      Australia and in their homelands. RESULTS: Suicide rates showed a decreasing time
      trend among all COB groups for both genders in Australia. The lowest suicide
      rates were found during 2004-2006, compared to other year groups. Throughout the
      study period, males born in Eastern, Northern and Western Europe and New Zealand
      had the highest suicide rates in Australia. For females, the highest rates were
      among those born in Western Europe and the UK (including Ireland). Male and
      female migrants born in North Africa and the Middle East, Southern and Central
      Asia and South East Asia showed the lowest suicide rates. There was a significant
      correlation between male immigrant suicide rates by COB and the rates of their
      home countries. CONCLUSION: The patterns of suicide rates in immigrants were
      influenced by the social and cultural norms of their COB. The overall decrease in
      suicide risk among immigrants was particularly evident in males.

PMID- 22476117
TI  - [In brackets].

PMID- 22476118
TI  - [Increase of intraepithelial lymphocytes in patients with irritable bowel
      syndrome].
AB  - Several studies have shown increased numbers of intraepithelial lymphocytes
      (IEL), mast cells, enterochromaffin cells in colonic mucosa of patients with
      Irritable Bowel Syndrome (IBS). Many of these findings are based is based on
      immunohistochemistry results, which is not available in general hospitals. Our
      objective is to study the histological findings observed in colon biopsies from
      patients with IBS compared with a group without IBS, using only histochemistry.
      Twenty five (25) patients were included: 16 with IBS and 9 without IBS. We found
      increased numbers of IEL in patients with IBS (p=0,002). A group of patients with
      IBS (41.9%) who fulfilled histological criteria for lymphocytic colitis were
      excluded. There was no significant difference in mast cells, enterochromaffin
      cells or eosinophils.

PMID- 22476119
TI  - [Ciprofloxacin vs cefazolin in the prevention of infection in cirrhotic patients
      with gastrointestinal bleeding].
AB  - AIM: To determine if prophylaxis with cefazolin produces a significant reduction
      in infections in cirrhotic patients with gastrointestinal bleeding when compared
      with ciprofloxacin. METHODS: Randomized clinical trial. Patients 18 years or
      older with diagnosis of cirrhosis, gastrointestinal bleeding and no clinical or
      laboratory evidence of infection who were admitted to the gastrointestinal
      bleeding unit of HNERM between July 2008 and July 2010 were included. Patients
      were allocated to receive either i.v. ciprofloxacin 200 mg bid or i.v. cefazolin
      1 gm tid for 7 days. RESULTS: 98 patients were included, 53 in the cefazolin
      group and 45 in the ciprofloxacin one. Age average was 66 +/- 10 years, 61% were
      male, 59,2% had ascites. Overall rate of infections was 14,3% (14/98). Rebleeding
      rate was 8,1% and mortality 4,1%. There were no differences in age, sex, Child
      Pugh score, ascites, hepatic encephalopathy nor in billirubin, albumin, PT and
      creatinine levels between the study groups. Infection rate in the cefazolin
      groups was 11,3% while in the ciprofloxacin one 17,8% (p=0,398).When Child-Pugh A
      and patients without ascites were excluded of the analysis, the cefalozin group
      had 22,2% of infections and 26,9% in the ciprofloxacin one (p=0,757). CONCLUSION:
      there were no differences in infection rates between patients with prophylaxis
      with cefazolin and ciprofloxacin after an episode of gastrointestinal bleeding.

PMID- 22476120
TI  - [Choledocholithiasis in Edgardo Rebagliati Martins Hospital. Lima-Peru. 2010
      2011. Incidence, risk factors, diagnostic and therapeutic aspects].
AB  - OBJECTIVE: to determine the incidence, frequency of risk factors, diagnostic
      aspects (clinics, biochemical, and images) and therapeutic aspects of the
      choledocholithiasis. PATIENTS AND METHODS: Descriptive and prospective analysis
      of 51 patients who signed informed consent for study of choledocholithiasis by
      ERCP (endoscopic retrograde cholangiopancreatography). RESULTS: Of the 51
      patients, 36 (70.6%) confirmed choledocholithiasis by ERCP. Its incidence was
      10.4%. The mean age was 63.75 years, BMI 25.59 kg/m2 and 55.6% were women.
      Abdominal pain was present in 94.4% of patients. Total bilirubin in the group
      with choledocholithiasis was 5.8 mg / dl at baseline and 4.2 mg / dl in
      hospitalization. 11.1% debuted with pancreatitis and 30.6% with cholangitis. In
      68.7% of patients with cholangitis was confirmed choledocholithiasis by ERCP. The
      specificity of ultrasound was 0.80 (95% CI 0.6- 1). The specificity of the
      nuclear magnetic resonance was 0.25 (95% CI 0.17-0.67). Of the 51 patients with
      ERCP, 4 (7.80%) do pancreatitis, 1(1.96%) cholangitis and 2 (3.92%) bleeding
      CONCLUSIONS: Choledocholithiasis occurs in older people, female and overweight
      with an incidence of 10.4%. Abdominal pain is the most common symptom. A total
      bilirubin more tan 4mg/dl occurs in patients with choledocholithiasis. The
      complications of choledocholithiasis (pancreatitis and cholangitis) were more
      frequent than reported in the literature. Both the specificity of cholangitis for
      choledocholithiasis, the specificity of ultrasound and the specificity of the
      nuclear magnetic resonance were lower than reported in the literature. ERCP
      complications were slightly higher than that reported in the literature.

PMID- 22476121
TI  - [Factors related to therapeutic failure in the extraction of bile duct  stones
      for endoscopic retrograde colangiopancreatography ERCP].
AB  - OBJECTIVE: Determine the factors that contribute to the technical difficulty of
      endoscopic clearance of common bile duct (CBD) stones in patients that underwent
      endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Prospective study
      included 90 patients, who underwent ERCP and an endoscopic sphincterotomy for the
      extraction of CBD stone. Between April 2009 and March 2010 at Arzobispo Loayza
      National Hospital. The technical difficult of CBD stone removal was graded in:
      easy (1 to 8 attempts) and difficult ( more than 8 attempts or failed). RESULTS:
      In the bivariate analysis, we found that factors which are related to the degree
      of difficulty were: stone greater than or equal to 15 mm, OR = 19.8, CI (5.7 -
      68.6); common bile duct greater than or equal to 15 mm, OR= 12.8, CI (3.7 - 44.3)
      and the use of mechanical lithotripsy, OR= 18.6, CI (1.9 -179). No association
      was found between the difficulty of the clearance of stone with: age, previous
      cholecystectomy, number of stones, stone impaction, periampullary diverticulum,
      sharper distal common bile duct angulation and shorter arm of common bile duct
      angulation. CONCLUSIONS: Complete clearance of common bile duct stone was
      technically more difficult in patients with: stone greater than or equal to 15
      mm, diameter of common bile duct greater than or equal to 15 mm and with the use
      of mechanical lithotripsy.

PMID- 22476123
TI  - [Experience with a biological plug for biological in complex anal fistula].
AB  - Treatment of complex anal fistula is a surgical challenge because the risk of
      sphincter injury with the possibility of developing fecal incontinence. There are
      many techniques for the treatment of anal fistulas such as fistulotomy,
      fistulectomy, seton, endorectal advancement flap and fibrin glue, with different
      rates of recurrence and fecal incontinence. The biologic plug Surgisis(r) AFP
      it's being used since 2006 and produces the closure of the fistula in
      approximately 12 weeks, without surgery, by replacement of the fistulous tract by
      cells of the patient, apparently having advantages over other techniques.We
      retrospectively reviewed the results of 46 patients with complex anorectal
      fistula treated with the biological plug over a period of 4 years. Of these, 34
      were men (73.9%) and 12 women, the mean age was 47.2 years. According the type of
      fistula, 41 were recurrent fistulas (89.1%) and 5 high transsphincteric fistulas
      (10.8%). Patients underwent surgery on average 2.2 times previously. The anal
      fistula plug was successful in 73.9% of cases with a median follow-up 29.8
      months. Use of anal fistula plug Surgisis(r) AFP is a new alternative with
      acceptable results in terms of recurrence comparable to other techniques, but
      with no incontinence.

PMID- 22476122
TI  - [Intraoperative events unexpected and conversion in patients laparoscopic
      cholecystectomy: male and independent risk factor].
AB  - BACKGROUND: Studies have been done trying to confirm the impression that
      laparascopic cholecystecotmy tends to be more complicacted and takes longer in
      men than in women. The analysis of sex as an independent risk factor has been
      done in various studies with mixed results. AIMS: To assess if male gender is an
      independent risk factor for unexpected intraoperative events, conversion and
      longer operating time in a restrospective cohort based on a population of 1029
      patients from one surgeon in a national hospital in Lima, from 1996 to 2010.
      METHODS: The relationship between three variables (unexpected intraoperative
      events, operative time and conversion) and male gender was analyzed in 1023
      patients (151 male, 872 female). Multivariate analysis was performed for two of
      these variables (unexpected intraoperative events and operating time). RESULTS:
      Male gender had an adjusted RR of 1.22 [1.05 - 1.42] (p= 0.007) for unexpected
      intraoperative events. Male gender had an adjusted RR of 1.11 [1.00 - 1.25] (p=
      0.048) for increased operating time compared to women. CONCLUSIONS: Our study
      shows that male gender is an independent risk factor for unexpected
      intraoperative events and longer operating time.

PMID- 22476124
TI  - [Validation of an instrument to measure the level of knowledge of non alcoholic
      fatty liver in general medical doctors in Chiclayo, Peru].
AB  - Nonalcoholic fatty liver disease (NAFLD) is a prevalent disease in daily
      practice. Most General medical do not know how to make a proper diagnosis,
      treatment and prognosis of this disease. In addition, there were no studies, nor
      an instrument that measures the level of knowledge about NAFLD, so we found it
      necessary to conduct this research. OBJECTIVE: To design and validate a
      questionnaire to determine the level of knowledge of nonalcoholic fatty liver
      disease (NAFLD) in general practitioners in the districts of Chicago and La
      Victoria since January to August 2011. METHODS: We designed a questionnaire of 13
      questions; we analyzed the content validity through expert assessment and
      construct validity using factor analysis. We assessed the reliability of the
      questionnaire examining the internal consistency by Cronbach's alpha method and
      test-retest reliability by intraclass correlation coefficient (ICC). The pilot
      test was conducted, interviewing 15 general medical. RESULTS: Cronbach's alpha of
      the questionnaire was 0.77. The value of Kaiser - Meyer-Olkin was 0.091 and
      Bartlett's sphericity test was 0.003, so we did not perform factor analysis, the
      intraclass correlation had a value of 77%. Also passing score for diagnosis was
      greater than 4.6 points and for treatment and prognosis than 4 points.
      CONCLUSIONS: This study provided an instrument with high reliability to measure
      the level of awareness of NAFLD in General Medical.

PMID- 22476125
TI  - [Assessment of the indications of colonoscopy in the prediction of colon cancer
      diagnosis].
AB  - OBJECTIVE: To determine the diagnostic value of colonoscopy indications as
      predictors of colorectal cancer (CRC). METHODS: A retrospective study of
      colonoscopy indications in Centenary Peruvian Japanese Clinic from 2006 to 2010
      was performed. Diagnosis of CRC was considered as dependent variable whereas
      colonoscopy indications were considered as independent variables. For each
      indication we calculated the sensitivity (S), positive predictive value (PPV),
      positive likelihood ratio (LR+) and number of colonoscopies needed to diagnose a
      case of CRC (NND). RESULTS: Of the 2290 colonoscopies analyzed, 58 (2.5%) had
      colorectal cancer, with a mean age of 66.5 ?} 12.4 years (range 27-84) of whom
      89.7% were older than 50 years. The indications with greatest PPV were abdominal
      tumor (20.0%), liver metastases (16.7%), hematochezia (12.2%), suspicious
      radiological image (10.0%), constitutional syndrome (8.3%) and anemia (7.9%). The
      indications with greatest LR+ were liver abdominal tumor (9.62), liver metastases
      (7.70), hematoquezia (5.33), suspicious radiological image (4.28), (3.5) and
      anemia (3.31). The NND was 5 in hematoquezia and 10 in anemia, while others
      indications had negative NND or no significant. CONCLUSIONS: Indications of
      abdominal tumor, liver metastases, non-distal rectal bleeding, suspicious
      radiological image, constitutional syndrome and anemia were associated with
      colorectal cancer diagnosis. Non-distal rectal bleeding and anemia had adequate
      NND in diagnosis of colorectal cancer.

PMID- 22476126
TI  - Endoscopy Ultra- Sonography -guided biliary drainage in the surgical -endoscopy
      era.
AB  - BACKGROUND: US-guided hepatico - gastrostomy, choledocho-duodenostomy and
      choledocho-antrostomy are advanced procedures on biliary and pancreatic endoscopy
      and together make up the echo-guided biliary drainage. Hepatico - gastrostomy is
      indicated in cases of hiliar obstruction, while the procedure of choice is
      choledocho - duodenostomy in distal lesions. Both procedures must be done only
      after unsuccessful ERCP. AIMS: To clarify to the readers about indication of
      these procedures, they must be made under a multidisciplinary view while sharing
      information with the patient or legal guardian. METHODS: All series cases report
      and selected cohort studies were selected according to the DDTS system in which
      key words were EUS biliary drainage, choledocho-duodenostomy, hepatico
      gastrostomy, EUS, palliation and pancreatic biliary advanced cancer. RESULTS:
      Separately it was stated definition on the EUS biliary drainage procedures and it
      includes the techniques details and critical analysis. CONCLUSION: Hepatico-
      gastrostomy and Choledocho- duodenostomy are feasible when performed by
      endoscopists with expertise in bilio pancreatic endoscopy and advanced echo
      endoscopy and should be performed currently under rigorous protocol in
      educational institutions.

PMID- 22476127
TI  - [Hepatic solitary fibrous tumor].
AB  - Solitary fibrous tumor is a very uncommon mesenchymal neoplasia in the liver. We
      report a new case in 52 year old patient. The tomographic image revealed a solid,
      well delimitated tumor, localized at the right hepatic lobe. Macroscopically, it
      had rounded borders, was expansive and white. Microscopically it had a spindle
      cell pattern with extensive areas of hyalinization and hemangiopericytic vessels;
      it was positive with inmunohistochemestry markers for CD34, CD99 and Bcl-2.
      Despite its rarity, solitary fibrous tumor should be considered among the
      differential diagnosis of the spindle cell tumors of the liver.

PMID- 22476128
TI  - [Dysphonia as early presentation symptom in colonic perforation].
AB  - We report two cases with similar main complaints: dysphonia and subcutaneous
      cervical emphysema. After diagnosis procedures we identified pneumomediastinum,
      pneumoperitoneum and pneumoretroperitoneum caused by colonic perforation. Both
      patients underwent surgical treatment at Hospital Campo Aranuelo, Navalmoral de
      la Mata. Dysphonia and subcutaneous cervical emphysema are infrequent symptoms of
      presentation for occult gastrointestinal tract perforation or any retroperitoneal
      condition. Subcutaneous emphysema due to colonic perforation is extremely
      uncommon but it must to be considerate as a cause when its etiology remains
      unknown. Non iatrogenic subcutaneous emphysema is very rare in publications and
      is mostly associated with perforated sigmoid diverticulitis or carcinoma and the
      prognosis is poor Both patients underwent surgical treatment and also a wide
      spectrum antibiotic course. One of them needed respiratory support in the
      intensive care unit, and, in the outcome, he required a second surgical procedure
      to evacuate a residual abscess before discharge.

PMID- 22476129
TI  - [Conservative management of hernia mesh infection].
AB  - INTRODUCTION: Standard management of infected mesh advocates its removal, but
      this often results in a larger hernia than at the time of original repair. In
      this article we describe a novel approach to manage conservatively an infected
      prosthetic mesh. PATIENT AND METHODS: Mesh infection rate at our institution was
      1%. We describe 3 cases (inguinal, ventral and parastomal hernias) that presented
      prosthetic mesh infections. All the cases were satisfactorily managed with a
      conservative approach, consisting in wound opening and pressurized wound
      irrigation with gentamicin (80mg/8hours) and intravenous infusion of
      Amoxicilin/Clavulanic acid (875mg+125mg/8hours) during 7 days, achieving sterile
      cultures of the mesh surface in all the cases. A 3rd intention closure of the
      wound was performed. There is no clinical evidence of recurrent infection in any
      case. CONCLUSION: Conservative management of mesh infection, including drainage,
      antibiotic irrigation and wound closure, is a potential alternative to mesh
      removal.

PMID- 22476130
TI  - Interleukin-17 producing T helper cells are increased during natural Plasmodium
      vivax infection.
AB  - Recent evidences have demonstrated the importance of Th17 cells in host defense
      against infectious diseases. However, little is known about their role in
      parasitic infections. Here, we showed that uncomplicated acute vivax malaria
      induce a significant expansion of IL-17-producing CD4(+) T cells associated to a
      pro-inflammatory cytokine profile. Furthermore, we demonstrated a correlation
      between numbers of IL-17(+)CD4(+) T cells and circulating CD4(+) T-cells
      producing IFN-gamma, IL-10 and TGF-beta. Finally, correlations between number of
      these cells and morbidity or parasitemia were not detected. Further studies are
      underway to investigate whether IL-17-producing CD4(+) T cells are critically
      involved in the immunity against Plasmodium vivax infection.

PMID- 22476132
TI  - [Huge cystic tumor in the left upper abdomen].
AB  - ABTRACT: We report the case of a 71-year-old man with a cystic tumor in the left
      upper abdomen and a long-standing history of symptoms. After completing clinical
      tests and imaging studies a laparotomy was performed. The tumor was removed
      together with the first jejunal loop and bowel reconstruction was completed by
      hand-sewn anastomosis. Histopathological analysis revealed a gastrointestinal
      stromal tumor classified as high risk.

PMID- 22476133
TI  - [Recruiting multicenter surgical studies in Germany].

PMID- 22476131
TI  - Ventral and dorsal fiber systems for imagined and executed movement.
AB  - Although motor imagery is an entirely cognitive process, it shows remarkable
      similarity to overt movement in behavioral and physiological studies. In
      concordance, brain imaging studies reported shared fronto-parietal sensorimotor
      networks commonly engaged by both tasks. However, differences in prefrontal and
      parietal regions point toward additional cognitive mechanisms in the context of
      imagery. Within the perspective of a general dichotomization into dorsal and
      ventral processing streams in the brain, the question arises whether motor
      imagery and overt movement could differentially involve the dorsal or ventral
      system. Therefore, we combined fMRI and DTI data of 20 healthy subjects to
      analyze the anatomical characteristics of connecting fronto-parietal association
      pathways of imagined and overt movements. We found a dichotomy of fiber pathways
      into dorsal and ventral systems: the superior longitudinal fascicle (SLF II-III)
      was found to connect frontal and parietal regions involved in both overt and
      imagined movements, whereas a ventral tract via the extreme/external capsule
      (EmC/EC) connects cortical regions specific for motor imagery that were situated
      more anteriorly and posteriorly. We suppose that motor imagery-related
      kinesthetic emulations are embedded into dorsal sensorimotor networks, and
      imagery-specific cognitive functions are implemented in the ventral system. These
      findings have implications for models of motor cognition.

PMID- 22476134
TI  - [Thoracic aortic aneurysm].
AB  - Thoracic aortic aneurysms (TAA) are the most common pathology of the thoracic
      aorta. TAA are occuring with increasing incidence (10.4 cases per 100,000 person
      years) and are most commonly caused by atherosclerosis. There are also
      hereditary, inflammatory and infectious pathogenic factors. A TAA initially
      causes no symptoms and is therefore usually diagnosed as an incidental finding.
      Computed tomography angiography (CTA) and magnetic resonance angiography (MRA)
      are the diagnostic tools of choice for diagnosis and treatment planning. The mean
      growth rate of TAA is estimated to be 0.10 to 0.42 cm per year. A diameter of 6
      cm is considered to be an indication for surgery. Besides medicinal therapy,
      thoracic endovascular aortic repair (TEVAR) nowadays offers certain advantages
      compared to conventional open repair. The same applies to the region of the
      aortic arch. Follow up examinations after TEVAR are of major importance in order
      to ensure long-term therapeutic success.

PMID- 22476136
TI  - Two azido-bridged cobalt(II) coordination polymers with nicotinate co-ligand:
      synthesis, structures and magnetic properties.
AB  - By utilizing nicotinic acid as a co-ligand, two new azido-bridged cobalt(II)
      complexes with the formulae [Co(2)(N(3))(nic)(2)Cl(H(2)O)](n) (1) and
      [Co(N(3))(nic)](n) (2) (nic = nicotinate) have been synthesized under
      solvothermal condition and structurally characterized. Complex 1 exhibits a rare
      three-dimensional (3D) Kagome topology with [Co4] units as connecting nodes.
      Complex 2 is also a 3D structure which contains 1D Co(II)-MU-1,1-azido chains as
      rod-shaped SBUs. Magnetic data analysis shows that ferromagnetic coupling intra
      [Co4]-cluster and antiferromagnetic interaction inter-[Co4]-cluster exists in
      complex 1, while complex 2 exhibits metamagnetism with a critical field of 5.5
      kOe.

PMID- 22476135
TI  - Associations of prenatal exposure to organophosphate pesticide metabolites with
      gestational age and birth weight.
AB  - BACKGROUND: Prenatal exposure to organophosphate (OP) insecticides, a widely used
      class of pesticides, may be associated with decreased gestational age and lower
      birth weight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme
      genotypes may modify the relationships between OP exposure and perinatal
      outcomes. OBJECTIVE: We examined the relationship of prenatal OP insecticide
      exposure, measured using urinary dialkyl phosphate (DAP) metabolite
      concentrations, with gestational age and birth weight. METHODS: We measured the
      concentrations of six nonspecific DAP metabolites of OP insecticides in two
      maternal spot urine samples collected in a prospective birth cohort. We performed
      multivariable regression to examine associations between the sum of six DAP
      concentrations (SigmaDAP) with gestational age and birth weight. We also examined
      whether these associations differed according to infant PON1(192) and PON1(-108)
      genotypes. RESULTS: Among 306 mother-infant dyads, a 10-fold increase in SigmaDAP
      concentrations was associated with a decrease in covariate-adjusted gestational
      age [-0.5 weeks; 95% confidence interval (CI): -0.8, -0.1] and birth weight (-151
      g; CI: -287, -16); the decrements in birth weight were attenuated after adjusting
      for gestational age. The relationship between SigmaDAP concentrations and
      gestational age was stronger for white (-0.7 weeks; CI: -1.1, -0.3) than for
      black (-0.1 weeks; 95% CI: -0.9, 0.6) newborns. In contrast, there was a greater
      decrease in birth weight with increasing urinary SigmaDAP concentrations for
      black (-188 g; CI: -395, 19) than for white (-118 g; CI: -296, 60) newborns.
      Decrements in birth weight and gestational age associated with SigmaDAP
      concentrations were greatest among infants with PON1(192QR) and PON(-108CT)
      genotypes. CONCLUSIONS: Prenatal urinary SigmaDAP concentrations were associated
      with shortened gestation and reduced birth weight in this cohort, but the effects
      differed by race/ethnicity and PON1(192/108) genotypes.

PMID- 22476137
TI  - (MU-1,2-dimethoxyethane-kappa2O:O')bis[(1,2-dimethoxyethane
      kappa2O,O')tris(1,1,1,5,5,5-hexafluoro-4-oxopent-2-en-2-olato
      kappa2O,O')cerium(III)].
AB  - A previous analysis [Fatila et al. (2012). Dalton Trans. 41, 1352-1362] of the
      title complex, [Ce(2)(C(5)HF(6)O(2))(6)(C(4)H(10)O(2))(3)], had identified it as
      Ce(hfac)(3)(dme)(1.5) according to the (1)H NMR integration [hfac = 1,1,1,5,5,5
      hexafluoroacetylacetonate (1,1,1,5,5,5-hexafluoro-4-oxopent-2-en-2-olate) and dme
      = 1,2-dimethoxyethane]; however, it was not possible to determine the
      coordination environment unambiguously. The structural data presented here reveal
      that the complex is a binuclear species located on a crystallographic inversion
      center. Each Ce(III) ion is coordinated to three hfac ligands, one bidentate dme
      ligand and one monodentate (bridging) dme ligand, thus giving a coordination
      number of nine (CN = 9) to each Ce(III) ion. The atoms of the bridging dme ligand
      are unequally disordered over two sets of sites. In addition, in two of the 
      CF(3) groups, the F atoms are rotationally disordered over two sets of sites.
      This is the first crystal structure of a binuclear lanthanide beta-diketonate
      with a bridging dme ligand.

PMID- 22476138
TI  - Dibromodiphenylstannane: isolated centrosymmetric dimers as a new structure motif
      for the intermolecular association of diorganotin(IV) dihalides.
AB  - In the crystalline state, the low-melting title compound [common name:
      diphenyltin(IV) dibromide], [SnBr(2)(C(6)H(5))(2)], consists of distorted
      tetrahedral molecules with compressed halide and enlarged carbon opening angles
      of 102.741 (9) and 123.53 (8) degrees , respectively, and Sn-C and Sn-Br bond
      lengths of 2.109 (2)/2.113 (2) and 2.4710 (3)/2.4947 (3) A, respectively.
      Intermolecular Sn...Br interactions, typical for diorganotin(IV) dihalides,
      R(2)SnHal(2) (with Hal = Cl, Br, I), and sterically less demanding organic groups
      lead to the formation of a hitherto unknown association pattern consisting of
      centrosymmetric dimers with an antiparallel orientation of the dipole moments and
      two weak intermolecular Sn...Br distances of 3.8482 (3) A between one of the two
      Br atoms and its neighbouring Sn atom, and vice versa. The second Br atom is not
      involved in intermolecular interactions and lies somewhat outside the association
      plane that, therefore, is not coplanar [interplanar angle = 1.750 (2) degrees ]
      with the tin-halide plane. The new structure motif of intermolecular tin-halide
      interaction can be classified as 2a(i), which indicates the number of molecules
      (i.e. '2') composing the oligomer, the antiparallel orientation (i.e. 'a') of
      their dipole moments and the centre of symmetry (i.e. 'i') giving rise to the
      association pattern.

PMID- 22476139
TI  - Poly[(MU3-benzene-1,4-dicarboxylato)di-MU-chlorido
      (triethanolamine)dicadmium(II)]: a cadmium-halide coordination polymer with a
      hydrogen-bonded three-dimensional framework.
AB  - The structure of the title compound,
      [Cd(2)(C(8)H(4)O(4))Cl(2)(C(6)H(15)NO(3))](n), consists of one-dimensional chains
      in which each centrosymmetric tetranuclear Cd(4)Cl(4)O(2) cluster is terminated
      by two chelating triethanolamine (teaH(3)) ligands but linked to two adjacent
      clusters through four bridging benzene-1,4-dicarboxylate (bdc) ligands. The
      tetranuclear Cd(4)Cl(4)O(2) clusters are held together via bridging Cl and O
      atoms. Three directional hydrogen bonds from the multi-podal hydroxy groups of
      the teaH(3) ligand stabilize and extend the one-dimensional chains into a three
      dimensional framework. All three hydroxy groups of the teaH(3) ligand form
      hydrogen bonds, illustrating the fact that the teaH(3) ligand can serve as an
      excellent hydrogen-bond donor.

PMID- 22476140
TI  - Di-MU-methanolato-bis[(eta4-tetrafluorobenzobarrelene)rhodium(I)].
AB  - The versatile synthetic precursor methanolate-bridged title rhodium complex,
      [Rh(2)(CH(3)O)(2)(C(12)H(6)F(4))(2)] or [Rh(MU-OCH(3))(tfbb)](2) [tfbb =
      tetrafluorobenzobarrelene or 3,4,5,6-tetrafluorotricyclo[6.2.2.0(2,7)]dodeca
      2(7),3,5,9,11-pentaene], has been structurally characterized. The asymmetric unit
      contains half a molecule that can be expanded via a twofold axis. The title
      compound has been shown to be a dinuclear rhodium complex where each metal centre
      is coordinated by two O atoms from two bridging methanolate groups and by the
      olefinic bonds of a tfbb ligand. Comparison of the bite angles of tfbb,
      norbornadiene (nbd) and cyclooctadiene (cod) olefins in their eta(4)-coordination
      to rhodium reveals similarities between the tfbb and nbd ligands, which are much
      more rigid than cod. The short distance found between the distorted square-planar
      metal centres [2.8351 (4) A] has been related to the syn conformation of the
      folded core 'RhORhO' ring.

PMID- 22476141
TI  - Two centrosymmetric dinuclear phenanthroline-copper(II) complexes with 3,5
      dichloro-2-hydroxybenzoic acid and 5-chloro-2-hydroxybenzoic acid.
AB  - The title compounds, bis(MU-3,5-dichloro-2-oxidobenzoato)
      kappa(3)O(1),O(2):O(2);kappa(3)O(2):O(1),O(2)-bis[(3,5-dichloro-2-hydroxybenzoic
      acid-kappaO(1))(1,10-phenanthroline-kappa(2)N,N')copper(II)],
      [Cu(2)(C(7)H(2)Cl(2)O(3))(2)(C(7)H(4)Cl(2)O(3))(2)(C(12)H(8)N(2))(2)], (I), and
      bis(MU-5-chloro-2-oxidobenzoato)-kappa(3)O(1),O(2):O(1);kappa(3)O(1):O(1),O(2)
      bis[(5-chloro-2-hydroxybenzoic acid-kappaO(1))(1,10-phenanthroline
      kappa(2)N,N')copper(II)] ethanol monosolvate,
      [Cu(2)(C(7)H(3)ClO(3))(2)(C(7)H(5)ClO(3))(2)(C(12)H(8)N(2))(2)].C(2)H(6)O, (II),
      contain centrosymmetric dinuclear complex molecules in which Cu(2+) cations are
      surrounded by a chelating 1,10-phenanthroline ligand, a chelating 3,5-dichloro-2
      oxidobenzoate or 5-chloro-2-oxidobenzoate anionic ligand and a monodentate 3,5
      dichloro-2-hydroxybenzoic acid or 5-chloro-2-hydroxybenzoic acid ligand. The
      chelating benzoate ligand also bridges to the other Cu(2+) ion in the molecule,
      but the O atom involved in the bridge is different in the two complexes, being
      the phenolate O atom in (I) and a carboxylate O atom in (II). The bridge
      completes a 4+1+1 axially elongated tetragonal-bipyramidal arrangement about each
      Cu(2+) cation. The complex molecules of both compounds are linked into one
      dimensional supramolecular chains through O-H...O hydrogen bonds.

PMID- 22476142
TI  - Distinct chiral units from an axially prochiral ligand in a photoluminescent
      zinc(II)-organic complex.
AB  - The asymmetric unit of the title compound, poly[(dimethylamine-kappaN)[MU(3)-(E)
      2,6-dimethyl-4-styrylpyridine-3,5-dicarboxylato
      kappa(3)O(3):O(3'):O(5)]zinc(II)], [Zn(C(17)H(13)NO(4))(C(2)H(7)N)](n), consists
      of one crystallographically independent distorted tetrahedral Zn(II) cation, one
      (E)-2,6-dimethyl-4-styrylpyridine-3,5-dicarboxylate (mspda(2-)) ligand and one
      coordinated dimethylamine molecule. Two S- and R-type chiral units are generated
      from the axially prochiral mspda(2-) ligand through C-H...O hydrogen bonds. The R
      type chiral units assemble a left-handed (M) Zn-mspda helical chain, while the
      right-handed (P) Zn-mspda helical chain is constructed from neighbouring S-type
      chiral units. The P- and M-type helical chains are interlinked by carboxylate O
      atoms to form a one-dimensional ladder. Interchain N-H...O hydrogen bonds extend
      these one-dimensional ladders into a two-dimensional supramolecular architecture.
      The title compound exhibits luminescence at lambda(max) = 432 nm upon excitation
      at 365 nm.

PMID- 22476143
TI  - Absolute configuration of strictosidinic acid.
AB  - The absolute configuration of strictosidinic acid, (2S,3R,4S)-3-ethenyl-2-(beta-D
      glucopyranosyloxy)-4-{[(1S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl]methyl}
      3,4-dihydro-2H-pyran-5-carboxylate, was determined from its sodium chloride
      trihydrate, poly[[diaqua((2S,3R,4S)-3-ethenyl-2-(beta-D-glucopyranosyloxy)-4
      {[(1S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-1-yl]methyl}-3,4-dihydro-2H
      pyran-5-carboxylate)sodium] chloride monohydrate],
      {[Na(C(26)H(32)N(2)O(9))(H(2)O)(2)]Cl.H(2)O}(n). The strictosidinic acid molecule
      participates in intermolecular hydrogen bonds of the O-H...O and O-H...Cl types.
      The solid-state conformation was observed as a zwitterion, based on a charged
      pyridine N atom and a carboxylate group, the latter mediating the packing through
      coordination with the sodium cation.

PMID- 22476144
TI  - A one-dimensional coordination polymer based on a di-Schiff base supported
      trinuclear CuII subunit.
AB  - A novel one-dimensional Cu(II) coordination polymer, catena-poly[bis(MU(4)-3-{[2
      (3-hydroxy-2-oxidobenzylidene)hydrazinylidene]methyl}benzene-1,2
      diolato)dimethanoltricopper(II)], [Cu(3)(C(14)H(10)N(2)O(4))(2)(CH(3)OH)(2)](n),
      (I), was constructed with a di-Schiff base supported centrosymmetric trinuclear
      Cu(II) subunit. In the subunit, two peripheral symmetry-related Cu(II) cations
      have square-pyramidal CuNO(4) geometry and the central third Cu(II) cation lies
      on an inversion centre with octahedral CuN(2)O(4) geometry. In (I), each
      partially deprotonated di-Schiff base 3-{[2-(3-hydroxy-2
      oxidobenzylidene)hydrazinylidene]methyl}benzene-1,2-diolate ligand (Hbcaz(3-))
      acts as a heptadentate ligand to bind the Cu(II) centres into chains along the a
      axis. A centrosymmetric Cu(2)O(2) unit containing an asymmetrically bridging O
      atom, being axial at one Cu atom and equatorial at the other Cu atom, links the
      trinuclear Cu(II) subunit into a one-dimensional chain, which is reinforced by
      intramolecular phenol-methanol O-H...O and methanol-phenolate O-H...O hydrogen
      bonds. Interchain pi-pi stacking interactions between pyrocatechol units, with a
      distance of 3.5251 (18) A, contribute to the stability of the crystal packing.

PMID- 22476145
TI  - 3,5-diphenyl-1,2,4-triazin-6(1H)-one: synthesis, and X-ray and DFT-calculated
      structures.
AB  - The title compound, C(15)H(11)N(3)O, (I), was obtained by the air oxidation of
      3,5-diphenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one. In the crystal structure, (I)
      forms centrosymmetric hydrogen-bonded dimers through pairs of N-H...N hydrogen
      bonds. The molecular structure of (I) deviates somewhat from planarity in the
      crystalline state, whereas a density functional theory (DFT) study predicts a
      completely planar conformation (C(s) point-group symmetry) for the isolated
      molecule. The solid-state conformation of (I) is stabilized by intramolecular
      hydrogen bonds, viz. one C-H...O interaction, which forms a six-membered ring,
      and three C-H...N interactions that each form five-membered rings. To estimate
      the influence of the intramolecular hydrogen-bonded rings on the aromaticity of
      the phenyl rings, the HOMA (harmonic oscillator model of aromaticity) descriptor
      of pi-electron delocalization has been calculated for conformations of (I) with
      and without intramolecular hydrogen bonds. In the planar conformation of (I), the
      HOMA values for both benzene rings are lower than in hypothetical conformations
      without intramolecular hydrogen bonds.

PMID- 22476146
TI  - Alkyl-chain disorder in tetraisohexylammonium bromide.
AB  - Tetraisohexylammonium bromide [systematic name: tetrakis(4-methylpentyl)azanium
      bromide], C(24)H(52)N(+).Br(-), is a powerful structure II clathrate hydrate
      crystal-growth inhibitor. The crystal structure, in the space group P3(2)21,
      contains one ammonium cation and one bromide anion in the asymmetric unit, both
      on general positions. At 100 K, the ammonium cation exhibits one ordered isohexyl
      chain and three disordered isohexyl chains. At 250 K, all four isohexyl chains
      are disordered. In an effort to reduce the disorder in the alkyl chains, the
      crystal was thermally cycled, but the disorder remained, indicating that it is
      dynamic in nature.

PMID- 22476147
TI  - Pseudopolymorphism in hydroxybenzophenones: the dihydrate of 2,2',4,4'
      tetrahydroxybenzophenone.
AB  - A dihydrate pseudopolymorph of bis(2,4-dihydroxyphenyl)methanone,
      C(13)H(10)O(5).2H(2)O, (I), was obtained during polymorphism screening of
      hydroxybenzophenone derivatives. This structure, in which the molecule sits on a
      twofold axis, was compared with the known anhydrous form of (I) [Schlemper
      (1982). Acta Cryst. B38, 554-559]. The role of water in the crystal assembly was
      established on the basis of the known monohydrate pseudopolymorph of 3,4
      dihydroxybenzophenone [Landre, Souza, Correa, Martins & Doriguetto (2010). Acta
      Cryst. C66, o463-o465].

PMID- 22476148
TI  - 6-bromoindigo dye.
AB  - 6-Bromoindigo (MBI) [systematic name: 6-bromo-2-(3-oxo-2,3-dihydro-1H-indol-2
      ylidene)-2,3-dihydro-1H-indol-3-one], C(16)H(9)BrN(2)O(2), crystallizes with one
      disordered molecule in the asymmetric unit about a pseudo-inversion center, as
      shown by the Br-atom disorder of 0.682 (3):0.318 (3). The 18 indigo ring atoms
      occupy two sites which are displaced by 0.34 A from each other as a result of
      this packing disorder. This difference in occupancy factors results in each atom
      in the reported model used to represent the two disordered sites being 0.08 A
      from the higher-occupancy site and 0.26 A from the lower-occupancy site. Thus, as
      a result of the disorder, the C-Br bond lengths in the disordered components are
      0.08 and 0.26 A shorter than those found in 6,6'-dibromoindigo (DBI) [Susse &
      Krampe (1979). Naturwissenschaften, 66, 110], although the distances within the
      indigo ring are similar to those found in DBI. The crystals are also twinned by
      merohedry. Stacking interactions and hydrogen bonds are similar to those found in
      the structures of indigo and DBI. In MBI, an interaction of the type C-Br...C
      replaces the C-Br...Br interactions found in DBI. The interactions in MBI were
      calculated quantum mechanically using density functional theory and the quantum
      theory of atoms in molecules.

PMID- 22476149
TI  - Two new XP(O)[NHC(CH3)3]2 phosphoramidates, with X = (CH3)2N and
      [(CH3)3CNH]2P(O)(O).
AB  - In N,N'-di-tert-butyl-N'',N''-dimethylphosphoric triamide, C(10)H(26)N(3)OP, (I),
      and N,N',N'',N'''-tetra-tert-butyl[oxybis(phosphonic diamide), [corrected]
      C(16)H(40)N(4)O(3)P(2), (II), the extended structures are mediated by P(O)...(H
      N)(2) interactions. The asymmetric unit of (I) consists of six independent
      molecules which aggregate through P(O)...(H-N)(2) hydrogen bonds, giving
      R(2)(1)(6) loops and forming two independent chains parallel to the a axis. Of
      the 12 independent tert-butyl groups, five are disordered over two different
      positions with occupancies ranging from 1/6 to 5/6. In the structure of (II), the
      asymmetric unit contains one molecule. P(O)...(H-N)(2) hydrogen bonds give S(6)
      and R(2)(2)(8) rings, and the molecules form extended chains parallel to the c
      axis. The structures of (I) and (II), along with similar structures having
      (N)P(O)(NH)(2) and (NH)(2)P(O)(O)P(O)(NH)(2) skeletons extracted from the
      Cambridge Structural Database, are used to compare hydrogen-bond patterns in
      these families of phosphoramidates. The strengths of P(O)[...H-N](x) (x = 1, 2 or
      3) hydrogen bonds are also analysed, using these compounds and previously
      reported structures with (N)(2)P(O)(NH) and P(O)(NH)(3) fragments.

PMID- 22476150
TI  - Aripiprazole salts. I. Aripiprazole nitrate.
AB  - The crystal structure of aripiprazole nitrate (systematic name: 4-(2,3
      dichlorophenyl)-1-{4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]butyl}piperazin
      1-ium nitrate), C(23)H(28)Cl(2)N(3)O(2)(+).NO(3)(-) or AripH(+).NO(3)(-), is
      presented and the molecule compared with the aripiprazole molecules reported so
      far in the literature. Bond distances and angles appear very similar, except for
      a slight lengthening of the C-NH distances involving the protonated N atom, and
      the main differences are to be found in the molecular spatial arrangement
      (revealed by the sequence of torsion angles) and the intermolecular interactions
      (resulting from structural elements specific to this structure, viz. the nitrate
      counter-ions on one hand and the extra protons on the other hand as hydrogen-bond
      acceptors and donors, respectively). The result is the formation of [100] strips,
      laterally linked by weak pi-pi and C-Cl...pi interactions, leading to a family of
      undulating sheets parallel to (010).

PMID- 22476151
TI  - A 2'-deoxycytidine long-linker click adduct forming two conformers in the
      asymmetric unit.
AB  - The title compound {systematic name: 4-amino-1-(2-deoxy-beta-D-erythro
      pentofuranosyl)-5-[6-(1-benzyl-1H-1,2,3-triazol-4-yl)hex-1-ynyl]pyrimidin-2(1H)
      one}, C(24)H(28)N(6)O(4), shows two conformations in the crystalline state, viz.
      (I-1) and (I-2). The pyrimidine groups and side chains of the two conformers are
      almost superimposable, while the greatest differences between them are observed
      for the sugar groups. The N-glycosylic bonds of both conformers adopt similar
      anti conformations, with chi = -168.02 (12) degrees  for conformer (I-1) and chi
      = -159.08 (12) degrees  for conformer (I-2). The sugar residue of (I-1) shows an
      N-type (C3'-endo) conformation, with P = 33.1 (2) degrees  and tau(m) = 29.5 (1)
      degrees , while the conformation of the 2'-deoxyribofuranosyl group of (I-2) is S
      type (C3'-exo), with P = 204.5 (2) degrees  and tau(m) = 33.8 (1) degrees . Both
      conformers participate in hydrogen-bond formation and exhibit identical patterns
      resulting in three-dimensional networks. Intermolecular hydrogen bonds are formed
      with neighbouring molecules of different and identical conformations (N-H...N, N
      H... O, O-H...N and O-H...O).

PMID- 22476152
TI  - 4,4'-(4,5-dimethyl-1,2-phenylene)bis(2-methylbut-3-yn-2-ol): structural variation
      in vicinal dialkynols.
AB  - The structure of the title compound, C(18)H(22)O(2), contains two non-equivalent
      molecules which differ primarily in the location of the -OH groups on opposite
      sides or on the same side of the molecular plane. Inversion-symmetric pairs of
      molecules form intermolecular O-H...O hydrogen-bonded tetrameric synthons that
      link non-equivalent molecules into an approximately square double layer parallel
      to (-102). Recently reported fluorinated analogues [Kane, Meyers, Yu, Gerken &
      Etzkorn (2011). Eur. J. Org. Chem. pp. 2969-2980] have significantly different
      structures of varying complexity that incorporate intramolecular hydrogen bonding
      and suggest that further study of structure versus substituents in vicinal
      dialkynols could be fruitful.

PMID- 22476153
TI  - Functional effects of CCL3L1 copy number.
AB  - Copy number variation (CNV) is becoming increasingly important as a feature of
      human variation in disease susceptibility studies. However, the consequences of
      CNV are not so well understood. Here, we present data exploring the functional
      consequences of CNV of CCL3L1 in 55 independent UK samples with no known clinical
      phenotypes. The copy number of CCL3L1 was determined by the paralogue ratio test,
      and expression levels of macrophage inflammatory protein-1alpha (MIP-1alpha) and
      mRNA from stimulated monocytes were measured and analysed. The data show no
      statistically significant association of MIP-1alpha protein levels with copy
      number. However, there was a significant correlation between copy number and
      CCL3L1:CCL3 mRNA ratio. The data also provide evidence that expression of CCL3
      predominates in both protein and mRNA, and therefore the observed variation of
      CCL3 is potentially more important biologically than that of CNV of CCL3L1.

PMID- 22476154
TI  - Exome sequencing identifies novel compound heterozygous mutations of IL-10
      receptor 1 in neonatal-onset Crohn's disease.
AB  - Inflammatory bowel disease is well recognized for a strong genetic involvement in
      its pathogenesis. Homozygous mutations in interleukin-10 receptor 1 (IL-10R1)
      identified by linkage analysis were shown to be involved in this disorder.
      However, the underlying molecular mechanism and the causal nature of the
      mutations in the disease process remain to be clarified. In this study, using
      whole exome sequencing, we identified novel compound heterozygous missense
      mutations in the extracellular domain of IL-10R1 in a Crohn's disease patient
      from a non-consanguineous family. These mutations did not affect IL-10R1
      expression, nor IL-10 binding. However, they abrogated IL-10R1 phosphorylation
      induced by IL-10, therefore leading to impaired STAT3 activation and suppression
      of inflammatory responses. After reconstitution with wild-type IL-10R1, the
      patient cells showed fully restored IL-10R function including IL-10-induced STAT3
      activation and expression of suppressor of cytokine signaling 3. Thus, our
      results demonstrated that the mutations in IL-10R1 extracellular domain impair IL
      10R1 activation rather than IL-10 binding, indicating these residues are
      important in IL-10 signal transduction through IL-10R1. The reconstitution data
      also confirmed the causality of the IL-10R1 mutations.

PMID- 22476156
TI  - Hepatitis C therapy update.
AB  - PURPOSE OF REVIEW: We review here the recent literature regarding hepatitis C
      treatment through January 2012. We discuss newly approved therapies and their
      clinical trial data and discuss what can be expected in this rapidly changing
      field. RECENT FINDINGS: Two new directly acting antiviral agents were approved in
      2011 for use in hepatitis C treatment, bringing shortened treatment durations,
      and increased treatment success to some patients with genotype 1 hepatitis C.
      Additional drugs using different viral targets are in development to further
      improve response rates, tolerance, and increase access to therapy. SUMMARY:
      Telaprevir and boceprevir were approved in 2011 for use against genotype 1
      hepatitis C, in combination with pegylated interferon and ribavirin. In most
      populations of genotype 1 patients, response rates are much improved but
      increased treatment related anemia has been seen. Additional options for therapy,
      including interferon-free regimens, are still needed and are under development.

PMID- 22476157
TI  - Liver.

PMID- 22476155
TI  - A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical
      manifestations characterized by the development of pathogenic autoantibodies
      manifesting in inflammation of target organs such as the kidneys, skin and
      joints. Genome-wide association studies have identified genetic variants in the
      UBE2L3 region that are associated with SLE in subjects of European and Asian
      ancestry. UBE2L3 encodes an ubiquitin-conjugating enzyme, UBCH7, involved in cell
      proliferation and immune function. In this study, we sought to further
      characterize the genetic association in the region of UBE2L3 and use molecular
      methods to determine the functional effect of the risk haplotype. We identified
      significant associations between variants in the region of UBE2L3 and SLE in
      individuals of European and Asian ancestry that exceeded a Bonferroni-corrected
      threshold (P<1 * 10(-4)). A single risk haplotype was observed in all associated
      populations. Individuals harboring the risk haplotype display a significant
      increase in both UBE2L3 mRNA expression (P=0.0004) and UBCH7 protein expression
      (P=0.0068). The results suggest that variants carried on the SLE-associated
      UBE2L3 risk haplotype influence autoimmunity by modulating UBCH7 expression.

PMID- 22476158
TI  - The Chicago criteria for esophageal motility disorders:  what has changed in the
      past 5 years?
AB  - PURPOSE OF REVIEW: The Chicago Classification for esophageal motility disorders
      was developed to complement the enhanced characterization of esophageal motility
      provided by high-resolution esophageal pressure topography (HREPT) as this new
      technology has emerged within clinical practice. This review aims to summarize
      the evidence supporting the evolution of the classification scheme since its
      inception. RECENT FINDINGS: Studies examining the specific esophageal motility
      disorders in regards to HREPT metrics, clinical characteristics, and responses to
      treatments have facilitated updates of the diagnostic scheme and criteria. These
      studies have demonstrated variation in treatment responses associated with
      subclassification of achalasia, the use of distal latency in the diagnosis of
      distal esophageal spasm, and the development of diagnoses including
      esophagogastric junction outflow obstruction and hypercontractile esophagus.
      SUMMARY: The diagnostic criteria described in the Chicago Classification have
      evolved to demonstrate a greater focus on distinct clinical phenotypes. Future
      evaluation of the natural history and treatment outcomes will assist in further
      refinement of this diagnostic scheme and management of esophageal motility
      disorders.

PMID- 22476159
TI  - Analysis of unstable behavior in a mathematical model for erythropoiesis.
AB  - We consider an age-structured model that describes the regulation of
      erythropoiesis through the negative feedback loop between erythropoietin and
      hemoglobin. This model is reduced to a system of two ordinary differential
      equations with two constant delays for which we show existence of a unique steady
      state. We determine all instances at which this steady state loses stability via
      a Hopf bifurcation through a theoretical bifurcation analysis establishing
      analytical expressions for the scenarios in which they arise. We show examples of
      supercritical Hopf bifurcations for parameter values estimated according to
      physiological values for humans found in the literature and present numerical
      simulations in agreement with the theoretical analysis. We provide a strategy for
      parameter estimation to match empirical measurements and predict dynamics in
      experimental settings, and compare existing data on hemoglobin oscillation in
      rabbits with predictions of our model.

PMID- 22476160
TI  - Autosomal recessive transmission of chorea-acanthocytosis confirmed.

PMID- 22476161
TI  - Physicians' beliefs about faith-based treatments for alcoholism.
AB  - OBJECTIVE: The study examined physicians' beliefs about faith-based alcohol
      treatments vis-a-vis Alcoholics Anonymous, pharmacologic treatment, and
      residential treatment. METHODS: A survey was mailed to a national sample of U.S.
      primary care physicians and psychiatrists. It included a brief vignette of a
      nominally religious 47-year-old man hospitalized for acute alcohol poisoning who
      requested addiction treatment. Physicians rated the likely effectiveness of three
      treatment methods: Alcoholics Anonymous, pharmacological therapy by an addiction
      specialist, and a residential program. Physicians were asked whether they would
      refer the patient to a faith-based program (beyond Alcoholics Anonymous) and
      whether an emphasis on spirituality is critical to 12-step program success.
      RESULTS: The response rate was 896 of 1,427 (63%) for primary care physicians and
      312 of 487 (64%) for psychiatrists. Psychiatrists were more likely to rate
      Alcoholics Anonymous as very effective (64% versus 57% of primary care
      physicians), more likely to rate residential treatment as very effective (47%
      versus 38% of primary care physicians), and more likely to rate pharmacologic
      therapy as very effective (31% versus 22% of primary care physicians).
      Psychiatrists and primary care physicians were equally likely to consider
      referring the patient to a faith-based program (71% and 79%) and equally likely
      to believe that "an emphasis on spirituality is critical to the success of 12
      step programs" (81% and 85%). CONCLUSIONS: Psychiatrists were more optimistic
      than primary care physicians about all three treatments. Physicians in both
      specialties would refer even nominally religious patients to explicitly faith
      based programs (beyond Alcoholics Anonymous). Physicians' enthusiasm for faith
      based treatments highlights the need for scientific study of these treatments to
      determine which elements are most helpful for patients seeking recovery.

PMID- 22476162
TI  - Enhanced bistability by guest inclusion in Fe(II) spin crossover porous
      coordination polymers.
AB  - Inclusion of thiourea guest molecules in the tridimensional spin crossover porous
      coordination polymers {[Fe(pyrazine)[M(CN)(4)]} (M = Pd, Pt) leads to novel
      clathrates exhibiting unprecedented large thermal hysteresis loops of ca. 60 K
      wide centered near room temperature.

PMID- 22476163
TI  - Variation in the HIF1A gene in elite rowers.
AB  - The transcription factor hypoxia-inducible factor 1 (HIF1) is one of the key
      regulators of cellular metabolism. The aim of this study was to analyze the
      possible importance of the HIF1A Pro582Ser polymorphisms in rowing. One hundred
      twenty-seven male Polish rowers (both former and current competitors) were
      recruited for this study. Genotyping was carried out by polymerase chain
      reaction. Significance was assessed by Chi-square (chi(2)) analysis. The results
      obtained revealed that frequency of the HIF1A Pro/Ser genotype (32.28 vs. 18.91%;
      p = 0.006) and Ser allele (16.93 vs. 10.00%; p = 0.01) were significantly higher
      in the rowers compared with those in controls. The results obtained confirm the
      significance of the HIF1A gene as a useful genetic marker in rowing. This kind of
      information would presumably be applicable in a program to search for the most
      predisposed individuals and also in the planning of training programs.

PMID- 22476164
TI  - Caffeine gum and cycling performance:  a timing study.
AB  - The purpose of this study was to determine the most efficacious time to
      administer caffeine (CAF) in chewing gum to enhance cycling performance. Eight
      male cyclists participated in 5 separate laboratory sessions. During the first
      visit, the subjects underwent a graded exercise test to determine maximal oxygen
      consumption (V[Combining Dot Above]O(2)max). During the next 4 visits, 3 pieces
      of chewing gum were administered at 3 time points (120-minute precycling, 60
      minute precycling, and 5-minute precycling). In 3 of the 4 visits, at 1 of the
      time points mentioned previously, 300 mg of CAF was administered. During the
      fourth visit, placebo gum was administered at all 3 time points. The experimental
      trials were defined as follows: trial A (-120), trial B (-60), trial C (-5), and
      trial D (Placebo). After baseline measurements, time allotted for gum
      administration, and a standard warm-up, the participants cycled at 75%
      V[Combining Dot Above]O(2)max for 15 minutes then completed a 7-kJ.kg(-1) cycling
      time trial. Data were analyzed using a repeated measures analysis of variance.
      Cycling performance was improved in trial C (-5), but not in trial A (-120) or
      trial B (-60), relative to trial D (Placebo). CAF administered in chewing gum
      enhanced cycling performance when administered immediately prior, but not when
      administered 1 or 2 hours before cycling.

PMID- 22476165
TI  - The effect of motor imagery and static stretching on anaerobic performance in
      trained cyclists.
AB  - Athletes perform many different protocols as part of their warm-up routine before
      competition. Stretching has been suggested to decrease force and power
      production, whereas motor imagery (MI), the visualization of simple or complex
      motor activities in the absence of physical movement, may increase force and
      power production in young healthy individuals. Few studies have investigated
      either of these in trained individuals. No studies have compared the effects of
      static stretching (SS) with MI on anaerobic performance in trained cyclists. The
      purpose of this study was to examine the effects of SS compared with MI and quiet
      rest (QR) on anaerobic performance in trained cyclists. Thirteen trained cyclists
      (9 men: 4 women; aged 21 +/- 2 years) were assessed for height (1.76 +/- 0.07 m),
      weight (73.4 +/- 13 kg), % body fat (10.8 +/- 6.2%), and maximal oxygen
      consumption (V[Combining Dot Above]O(2)max of 42.0 +/- 5.6 ml.kg(-1).min(-1)) on
      a cycle ergometer. The participants performed 3 randomized sessions consisting of
      cycling for 30 minutes at 65% of V[Combining Dot Above]O(2)max before undergoing
      16 minutes of SS, MI, or QR followed by an anaerobic performance test. The SS
      consisted of 3 sets of 30-second stretches of the hamstrings, quadriceps, hip
      flexors, and piriformis. Imagery was based on the physical, environmental, task,
      learning, emotion, and perspective approach and was conducted by a trained
      technician. Both relative and absolute powers, and peak revolutions per minute,
      were quantified using the Wingate anaerobic threshold test. No significant
      interactions existed among SS, MI, and QR for relative peak power, absolute peak
      power, or peak RPM. In disagreement with current literature, this study suggests
      that neither SS nor a single session of MI immediately affect anaerobic
      performance in trained cyclists. If an event is <30 seconds, then SS or MI may
      not affect performance.

PMID- 22476166
TI  - The use of heart rates and graded maximal test values to determine rugby union
      game intensities.
AB  - The aim of this study was to determine the intensities of university rugby union
      games using heart rates and graded maximal test values. Twenty-one rugby players
      performed a standard incremental maximal oxygen uptake (VO2max) test to the point
      of exhaustion in the weeks between 3 rugby matches. The heart rates that
      corresponded to the first and second ventilatory thresholds were used to classify
      the heart rates into low-, moderate-, and high-intensity zones. The heart rates
      recorded through heart rate telemetry during the matches were then categorized
      into the different zones. The average heart rates for the different intensity
      zones as well the percentages of the maximum heart rate (HRmax) were as follows:
      low, 141-152 b.min(-1) (76.2-82.0% HRmax); moderate, 153-169 b.min(-1) (82.7
      91.4% HRmax); and high, 170-182 b.min(-1) (91.9-100% HRmax). The percentages of
      time players spent in the different intensity zones were as follows: 22.8% for
      the low-intensity, 33.6% for the moderate-intensity, and 43.6% for the high
      intensity zones. The dependant t-test revealed significant differences (p < 0.05)
      between the low- and high-intensity zones for the second halves, between the low-
      and moderate- as well as between the low- and high-intensity zones for the
      matches overall. To conclude, the results of the study showed that the above
      mentioned method can be used to determine the intensities of university rugby
      union games. It also revealed that university rugby games are categorized by
      significantly more high-intensity activities than was previously reported by
      other rugby match analyzing-related studies. Thus, sport scientists and
      conditioning coaches should concentrate more on high-intensity activities for
      longer periods during training sessions.

PMID- 22476167
TI  - The effects of tournament preparation on anthropometric and sport-specific
      performance measures in youth judo athletes.
AB  - The purpose of this study was to characterize the adaptations imposed by 4 weeks
      of precompetition judo training in youth athletes. It was hypothesized that
      anthropometric and sport-specific performance would improve during the
      preparation for a junior national championship event. Twenty youth athletes (mean
      +/- SD; chronological age: 13.1 +/- 3.2 years; training age: 5.3 +/- 3.5 years;
      judo experience: 7.8 +/- 2.5 hours per week) completed pretesting and posttesting
      procedures. Child (12 years old; n = 8) and adolescent (13 years old; n = 12)
      groups were evaluated to determine the anthropometric and sport-specific
      performance changes caused by 4 weeks of judo training conducted in preparation
      for the junior national championships. The child group showed an increase in
      flexibility (11.5%), and the adolescent group showed a decrease in skinfold
      thickness (-12.2%); increased jumping power (26.7%), force (7.7%), and velocity
      (19.0%); and improved judo-specific ability (-5.9%), as measured by the Special
      Judo Fitness Test (SJFT) index. Additionally, the SJFT index for all the study
      participants was shown to be inversely correlated to handgrip strength (r = 
      0.681), rope pull performance (r = -0.545), and jump height (r = -0.503). These
      results support the use of preparatory judo training in the improvement of
      anthropometric and sport-specific measures in adolescent athletes. Furthermore,
      the outcomes from this study provide direction for coaches and trainers in their
      efforts to impact physical performance and judo skills in children and
      adolescents through precompetition training.

PMID- 22476168
TI  - Effects of beta-alanine supplementation on sprint endurance.
AB  - Recent research has shown that beta-alanine (BA) supplementation can increase
      intramuscular carnosine levels. Carnosine is an intramuscular buffer, and it has
      been linked to improvements in performance, specifically during bouts of high
      intensity exercise that are likely limited by muscle acidosis. Therefore, the
      purpose of this study was to examine the effect of BA supplementation on sprint
      endurance at 2 different supramaximal intensities. Twenty-one anaerobically
      trained (rugby players [n = 4], wrestlers [n = 11], and recreationally strength
      trained athletes [n = 6]) college-aged men participated in a double-blind,
      placebo controlled study. The subjects performed an incremental VO2max test and 2
      sprint to exhaustion tests set at 115 and 140% of their VO2max on a motorized
      treadmill before (PRE) and after (POST) a 5-week supplementation period. During
      this time, the subjects ingested either a BA supplement or placebo (PLA) with
      meals. The subjects ingested 4 g.d(-1) of BA or PLA during the first week and 6
      g.d(-1) the following 4 weeks. Capillary blood samples were taken before and
      after each sprint to determine blood lactate response to the sprint exercise. No
      significant group (BA, PLA) * intensity (115%, 140%; p = 0.60), group by time
      (PRE, POST; p = 0.72), or group * intensity * time (p = 0.74) interactions were
      observed for time to exhaustion. In addition, similar nonsignificant observations
      were made for lactate response to the sprints (group * intensity, p = 0.43; group
      * time, p = 0.33, group * intensity * time, p = 0.56). From the results of this
      study, it was concluded that beta-alanine supplementation did not have a
      significant effect on sprint endurance at supramaximal intensities.

PMID- 22476169
TI  - On the crystallization of polymer composites with inorganic fullerene-like
      particles.
AB  - The effect of a sulfide fullerene-like particle embedded into a polymer has been
      studied by molecular dynamics simulations on the nanosecond time scale using a
      mesoscopic Van der Waals force field evaluated for the case of a spherical
      particle. Even in this approach, neglecting the atomistic features of the
      surface, the inorganic particle acts as a nucleation agent facilitating the
      crystallization of the polymeric sample. A consideration of the Van der Waals
      force field of multi-walled sulfide nanoparticles suggests that in the absence of
      chemical interactions the size of the nanoparticle is dominating for the adhesion
      strength, while the number of sulfide layers composing the cage does not play a
      role. 

PMID- 22476170
TI  - Unprecedented dithiolation of enals via their NHC-catalysed umpolung reaction
      with organic disulfides.
AB  - A novel one-pot N-heterocyclic carbene (NHC)-catalysed dithiolation of alpha,beta
      unsaturated aldehydes (enals) with organic disulfides is reported. The protocol
      involves homoenolate reactivity of enals, where the homoenolate attacks on the
      disulfide as a d(3) nucleophile followed by thioesterification to afford beta
      aryl/alkylsulfanyl thioesters with complete atom economy.

PMID- 22476171
TI  - Flow cytometric assessment of the protectants for enhanced in vitro survival of
      probiotic lactic acid bacteria through simulated human gastro-intestinal
      stresses.
AB  - The aim of this study was to apply flow cytometric (FCM) analysis to assess the
      use of sucrose and lecithin vesicles for the protection of probiotic lactic acid
      bacteria in response to the challenge of gastric acidity and bile salts. FCM
      analysis in combination with fluorescent probes carboxyfluorescein (cF) and
      propidium iodide was used to reveal the physiological heterogeneity in the
      stressed bacteria population. Three subpopulations (intact, stressed, and
      damaged) were differentiated by FCM in all six examined strains. Significant
      changes were observed in the presence of the selected protectants. The addition
      of 20 mM sucrose in the simulated gastric fluid substantially increased the
      number of intact cells over 20 folds and reduced the damaged subpopulation by
      half. The presence of 2 % (w/v) lecithin vesicles was shown to protect 50 % more
      intact cells from the challenge of bile salts. The improved survival as evaluated
      by FCM analysis was further assessed for the proliferation capacity by sorting a
      number of cells from each subpopulation on nutrient agar plate. The result
      confirmed conformity between the proliferation-based cultivability and the probe
      indicated viability in the samples of the intact and the damaged subpopulations.
      However, it also revealed the complexities of the stressed (injured)
      subpopulation. In conclusion, FCM analysis confirmed that the selected
      protectants could improve the survival of the probiotic strains in the simulated
      GI environments. The FCM analysis also proved to be a useful analytical tool for
      the probiotics research.

PMID- 22476172
TI  - [Launch to be measure with the impact factors].

PMID- 22476173
TI  - [Use of a rapid rotavirus test in prescription of antibiotics in acute diarrhea
      in pediatrics: an observational, randomized, controlled study].
AB  - OBJECTIVE: To determine the impact of a rapid and accurate rotavirus test in the
      emergency ward on the reduction of antibiotic prescription in children under 5
      years old with acute diarrhea at "Arzobispo Loayza National Hospital", Lima,
      Peru. MATERIAL AND METHODS: We performed an observational prospective randomized
      controlled study, from July 2008 to January 2009. Stool samples from patients
      with diarrhea lasting less than 5 days were analyzed. Out of 201 cases, 101 were
      classified in Group A (with fecal leukocytes test performed) and 100 in Group B
      (with fecal leukocytes test and rotavirus/adenovirus test performed). We aimed to
      associate the signs and symptoms with the decision of prescribing antibiotics and
      with hospitalization risk. RESULTS: Both groups were comparable with regard to
      age, weight and illness duration. In patients with rotavirus infection, fecal
      leukocytes were positive in 46.9% of cases. Frequency of antibiotic use was
      directly associated with the number of fecal leukocytes (P<0.0001). There was a
      higher risk of admission in the group positive to rotavirus than in the group
      negative to this agent (21.9% vs. 6.3, P<0.0001). No diarrhea-attributable deaths
      were reported. CONCLUSION: The use of rotavirus test in the pediatric emergency
      room decreased antibiotic prescription in children with diarrhea.

PMID- 22476174
TI  - [Flat, depressed and polypoid colorectal lesions: a comparative study using a
      index of histological advance].
AB  - BACKGROUND: It has been described that the histological changes in flat and
      depressed colon lesions are more advanced than the ones in polypoid lesions.
      OBJECTIVES: To compare the histological findings in flat or depressed (non
      polypoid) and elevated (polypoid) colon lesions. To validate the use of a newly
      developed Histological Advance Index to compare results. MATERIALS & METHODS:
      Prospective observational study. Population in study consisted of adult patients
      programmed for an elective colonoscopy at a private endoscopy center in Lima-
      Peru. Two groups: 417 found to have non polypoid lesions (which included flat,
      depressed and lateral spreading tumors or LST), and 405 with polypoid lesions.
      RESULTS: Total of 8,248 patients, with 417(5%) in the non polypoid group;
      368(4.5%) in the flat lesion group, 27(0.32%) in the depressed and 22 (0.26%)
      LSTs. According to our index, flat and polypoid lesions showed no difference in
      histological findings. LSTs had a more advanced histology and depressed lesions
      reached the highest index scores. Flat lesions were found more often in right
      colon compared with polypoid ones (31% vs 22%, p<0.01), with a higher percentage
      of serrated lesions (9% vs 2%, p<0.01) and high grade dysplasia (5% vs 3%, NS).
      In contrast, depressed lesions, showed high grade dysplasia in 3.7% (NS) but
      cancer in 18% (p<0.01) LSTs were found mainly in right colon and rectum, showing
      villous component in 23%(p< 0.01) and high grade dysplasia in 32%(p <0.01), but
      no cancer was found. CONCLUSIONS: Flat and polypoid lesions showed similar
      histological findings, but LSTs were found to have a higher prevalence of villous
      lesions and high grade dysplasia. Depressed lesions were found to have a higher
      prevalence of malignancy. Histological Advance Index proved to be a useful tool
      to compare groups and quantify differences. .

PMID- 22476175
TI  - A prospective randomized study comparing partially covered metal stent versus
      plastic multistent in the endoscopic management of patients with postoperative
      benign bile duct strictures: a follow-up above 5 years.
AB  - BACKGROUND: Self-expandable metal stents (SEMS) are often used for biliary
      drainage due to obstruction of neoplastic etiology, with better results than
      plastic stents, but seldom for biliary drainage of benign etiology. OBJECTIVE:
      Primary end point: Verify bile duct patency after placement of self-expandable
      metal and (multiple) plastic stents in patients with benign strictures resulting
      from bile duct surgery with follow-up above five years. Secondary end point:
      Evaluate long-term complication rate in patients with metal self-expandable and
      plastic stents. RESULTS: Self-expandable stents were placed in 15 patients and
      multiple plastic stents in 16. Mean age was 45 years with prevalence of female
      patients in both groups and no statistical difference between groups was observed
      (SEMS: 66.7%; plastic multistent: 62.5%; p=0.8). Complication rate resulting from
      stents occurred more often in the metal stent group (40% versus 25%; p=0.37). In
      the metal stent group, most frequent complications were hemorrhage (n=3; 20%),
      stent migration (n=2; 13.3%) and perforation (n=1; 6.7%). In plastic multistent
      group, most frequent complications were perforation (n:2; 12.5%), hemorrhage
      (n=1; 6.2%) and ulcer (n=1; 6.2%). Long-term patency rate after biliary drainage
      was higher in the self-expandable metal stent group, SEMS: 81.67% +/- 2.56; CI:
      76.47-86.54; plastic multistent: 71.88% +/- 2.93; CI: 66.08-77.27. CONCLUSION:
      The temporary passage of partially covered self-expandable metal stents is a
      feasible option for patients with benign bile duct strictures.

PMID- 22476176
TI  - [Impact of splenectomy and/or distal pancreatectomy in the prognosis of the
      proximal gastric cancer].
AB  - OBJECTIVES: Identify prognostic factors associated to total or proximal
      gastrectomy with or without splenectomy and / or distal pancreatectomy in patient
      with proximal gastric cancer. Evaluate the frequency of lymph node metastasis to
      the hilum and splenic artery, postoperative morbidity and mortality and the
      impact of lymphadenectomy of group 10 and 11 on long term survival. MATERIALS AND
      METHODS: We performed an observational, descriptive, longitudinal and
      retrospective study analyzing patients with diagnostic of proximal third gastric
      adenocarcinoma subjected to total or proximal gastrectomy with or without
      splenectomy or distal pancreatectomy in the service of Abdomen of the Instituto
      Nacional de Enfermedades Neoplasicas between 1990 and 2005. Overall survival for
      each of the groups was calculated using the Kaplan-Meier method, prognostic
      factors were evaluated using univariate and multivariate analysis. RESULTS: We
      studied 219 patients with proximal third gastric adenocarcinoma (cardias and
      bottom), of wich, according to inclusion criteria, only qualify 129 (N=129): 22
      (17.1%) were treated by gastrectomy alone, 79 (61.2%) gastrectomy associated
      witch splenectomy and 28 (21.7%) gastrectomy with distal pancreatosplenectomy,
      constituting three treatment groups. We compared the survival of each group and
      each factor analyzed, determining the following prognostic factors: lymph node
      metastasis (N2-N3), degree of differentiation, undifferentiated tumors and
      Borrmann III and IV tumors. Neither splenectomy or distal pancreatectosplenectomy
      improved survival compared to the gastrectomy alone. The morbidity and mortality
      was higher in patients with more aggressive but more aggressive surgery without
      significant value. CONCLUSIONS: The number of nodes removed in patients who had
      pancreatosplenectomy and /or splenectomy was higher, however, had no impact on
      survival at 5 years.

PMID- 22476177
TI  - [Frequency of proton pump inhibitor prescription based in clinical practice
      guidelines in hospitalized patients in two academic hospitals in Lima, Peru].
AB  - OBJECTIVES: To evaluate if Proton Pump Inhibitor (PPI) prescription is based in
      Clinical Practice Guidelines (CPG) in hospitalized patients at two academic
      hospitals of Lima. MATERIALS AND METHODS: The services of Intern Medicine,
      Tropical Medicine and General Surgery were visited. Therapeutic sheets and
      nursing transcript were checked. The prescription motifs were determined in
      patients who received PPI. These motifs were obtained according to a check list,
      which was made from different CPG. RESULTS: 54.57% of the PPI prescriptions in
      the two academic hospitals were not based in CPG. No statistic significant
      difference was found between the two academic hospitals in the PPI prescription
      based in CPG (p=0,208). Most of the prescriptions not base on CPG belong to the
      service of General Surgery (83.6%; p<0.0001). The main indication for the
      prescription of PPI based on CPG was prevention of NSAIDS induced gastric ulcers
      if advanced age (65.72%). CONCLUSIONS: There is a high rate of PPI overuse in two
      academic hospitals.

PMID- 22476178
TI  - [Associated risk factors in patients with gastric intestinal metaplasia with mild
      gastroduodenal disease. Is it always related to Helicobacter pylori infection?].
AB  - OBJECTIVE: This study aimed to assess the presence or absence of association of
      Helicobacter pylori infection (HP) as risk factor for gastric intestinal
      metaplasia (IM), and to determine concomitant cofactors. METHODS: A prospective,
      case-control study was performed from October 2010 to May 2011, in outpatients
      without significant gastroduodenal disease. The presence or absence of IM was
      diagnosed by gastric biopsies (case or control, respectively). H. Pylori
      infection, age, sex, smoking, alcohol drinking, family history of gastric cancer
      and bile reflux were evaluated. Odds ratios (ORs) and their 95% CIs were
      estimated by logistic regression. RESULTS: A total of 440 patients (88 cases and
      352 controls) were studied, with a mean age +/- SD of 44.3 +/- 15.7 years; 58.2%
      were women. Prevalence of HP infection was 51.6% in the population and 46.6% in
      patients with IM. The mean age was significantly higher in cases (56.5 years vs.
      39, p = 0.0005), whereas no differences in other variables studied. In bivariate
      analysis, only age >= 50 years was a risk factor (OR = 4.47, 95% CI 2.66-7.57),
      whereas in multivariate analysis the risk factors were age >= 50 years (OR =
      4.67, 95% CI 2.79-7.81), bile reflux (OR = 3.66, 95% CI 1.71-7.83) and history of
      alcohol drinking (OR = 2.31, 95% CI 1.33-4.03). HP infection showed an OR less <
      1 (OR = 0.85, 95% CI 0.51-1.41). CONCLUSIONS: Risk factors associated with the
      presence of IM in outpatients without significant gastroduodenal disease were age
      >= 50 years, bile reflux and a history of alcohol drinking in the population
      studied. H. Pylori infection was not associated as risk factor for IM.

PMID- 22476179
TI  - [Gastric cancer: epidemiologic profile 2001-2007 in Lima, Peru].
AB  - OBJECTIVE: To describe and compare the demographic and social characteristics as
      well as lifestyles of patients with gastric cancer against patients with other
      important gastric disorders, who attended at main reference health services in
      Lima, Peru. METHODS: Case control study, matched by sex and age + 2 years,
      applying a questionnaire to 96 cases with gastric cancer, and to 96 controls from
      September 2001 to November 2007. RESULTS: There were no significant differences
      about ethnicity; marital status; exposure to minerals, wood, and metal dusts;
      tobacco and alcohol; red meat consumption; salt addition; food temperature. 87,
      5% of the control group had lesions in the gastric antrum, and 73% of cases group
      had a tubular adenocarcinoma (56%) in the gastric antrum. There was no family
      history of cancer in 85% patients of cases group and 59% of controls, (with
      significant difference). There were significant differences in low scholarship
      level of cases, as well as for their mothers and fathers (OR 3.75, 3.9, and 3.49
      respectively), fruit or vegetables intake, milk or cheese consumption (minus of
      once a day) (OR 2, 3, 2, 57 and 2, 9 respectively), type of fuel for cooking
      (firewood, charcoal, and kerosene OR 5, 25), lack of use of refrigerator (OR 8,
      4). CONCLUSIONS: The profile of a gastric cancer patient was to proceed from the
      Andean zone (high altitude +3000 meters over sea level) and jungle, low education
      level (low socioeconomic level), low consumption of fruits, vegetables and milk,
      use of firewood, charcoal, or kerosene to cook, and no use of refrigerator. The
      most frequent histological diagnosis in the case group was tubular
      adenocarcinoma.

PMID- 22476180
TI  - [Constipation syndrome: methods for measuring the speed of intestinal transit].
AB  - In the present article, I remind what I presented, in a symposium performed in
      our Society on the constipation syndrome, in relation with the definition and the
      determinant factors of this syndrome, and, in addition, with the methods we have
      created to determine physiologically the velocity of the intestinal transit,
      specially colonic.

PMID- 22476181
TI  - [Spleen infarction and S hemoglobinopathies S in the high altitude lands].
AB  - The hemoglobin S is a consequence of the substitution of valine for glutamic acid
      at position 6 of beta globin chain. The problem arises when some individuals with
      Hb S is moved to the mountains and exposed to hypoxia. The decrease in oxygen
      saturation distorts the red blood cell with HbS-shaped crescent (sickle cell).
      Sickle cell (rigid and fragile) tends to adhere to the other red blood cells,
      generating a series of intravascular alterations that can lead to tissue ischemia
      or infarction. The spleen by type of movement and lack of lateral communications
      between the branches of the splenic artery was the most susceptible to sickle
      cell crisis. Splenic infarction at altitude corresponding to different
      circumstances can evolve in three stages: a) Acute (focal, uncomplicated), b)
      massive attack (more than 50% of parenchyma) and c) spontaneous rupture.Early
      diagnosis is crucial, allowing the quick and timely introduction of various
      measures, including adequate hydration and oxygenation continues until its
      evacuation to lower altitude locations. These measures would reduce the
      phenomenon of sickle and some patients may overcome this acute trance without
      major complications. The delay in diagnosis leads to action that can exacerbate
      tissue hypoxia and cause ischemia or infarction of various organs. A large
      population of black and mixed race of African descent living in the Peruvian
      coast, 10% and 2% respectively have hemoglobin S; Caucasian subjects with
      Mediterranean ancestry this hemoglobin also can carry. It is therefore essential
      to disseminate within the clinicians working in regions of high status and to
      thus prevent potentially fatal complications in patients with Hb S; is also
      essential to promote preventive measures for individuals with African or
      Mediterranean ancestry know their sickle cell status before traveling to places
      above 2,500 m.

PMID- 22476182
TI  - [Advances in surgical endoscopy: initial experience in endoscopic colonic
      submucosal dissection (ESD) in Costa Rica].
AB  - OBJECTIVES: To report the first case in Costa Rica of a colon tumor removed by
      endoscopic submucosal dissection (ESD). PATIENT AND METHOD: We describe the case
      of a 70-year-old man with a multilobulated 25 millimeters tumor located in the
      cecum, near the ileocecal valve, detected during a routine colonoscopic check-up.
      The biopsy revealed a tubular adenoma with high grade dysplasia and the patient
      underwent an endoscopic submucosal en-bloc dissection of the lesion. RESULTS: The
      procedure was successfully performed without complications such as bleeding or
      perforation. The operative time was 117 minutes. The histopathological analysis
      of the en-bloc specimen confirmed the diagnosis of high grade dysplasia with
      negative vertical and horizontal margins. CONCLUSION: Colon ESD is an attractive
      and safe treatment option for the removal of premalignant lesions and some types
      of early colon cancer.

PMID- 22476183
TI  - [Acute abdomen by gastric perforation due to foreign body from long stay: a case
      report].
AB  - The intake of foreign bodies is a common clinical entity in Gastroenterology,
      most of them are expelled spontaneously, but those that are long and sharp may
      cause complications in 1 to 5%, therefore requiring endoscopic extraction or
      surgical treatment sometimes. We report the case of a patient with a history of
      bulimia that came to the Guillermo Almenara Hospital for symptoms of acute
      abdominal pain due to gastric perforation by foreign body after many years there
      has been the intake and whose resolution was surgery.

PMID- 22476184
TI  - [Tension pneumoperitoneum as a complication of endoscopic ultrasound guided
      transgastric drainage of pancreatic pseudocyst: case report and review of the
      literature].
AB  - Pancreatic pseudocyst develops as a complication in some cases of pancreatitis.
      Endoscopic drainage is one of the available therapies, but it has limitations
      when a visible compression over the gastric or duodenal wall is not present, or
      when portal hypertension exists. Endoscopic ultrasonography allows for a guided
      approach even in cases where external compression over the gastrointestinal tract
      is barely visible or non-existent, and it also helps to prevent vascular injury
      during puncture of the fluid collection. The most frequent early complications
      related to cystogastrostomy and cystoduodenostomy are bleeding and
      pneumoperitoneum, and late complications are stent migration or occlusion, and
      infection. We report the case of a patient who developed tense pneumoperitoneum
      immediately after endoscopic ultrasound guided drainage of a pancreatic
      pseudocyst, and was treated conservatively. This is a severe event, and can be
      managed by emergency decompression through paracentesis as first line therapy.
      Most cases of pneumoperitoneum can be managed without surgery,but close
      observation is mandatory in order to timely detect and treat conditions needing
      surgical intervention. KEY WORDS: pancreatic.

PMID- 22476185
TI  - [Pneumoperitoneum, pneumoretroperitoneum, bilateral pneumothorax,
      pneumomediastinum and subcutaneous emphysema due ERCP].
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) has become an essential
      procedure in the diagnosis and treatment of biliopancreatic diseases.
      Complications of this procedure are potentially serious, being necessary to know
      how to recognize them for the application of the appropriate treatment. We report
      the case of a 79-year-old woman who developed a massive subcutaneous emphysema,
      bilateral pneumothorax, retropneumomediastinum, retropneumoperitoneum and
      pneumoperitoneum due to iatrogenic duodenal injury secondary to ERCP. The
      clinical suspicion for early diagnosis of iatrogenic injury after ERCP will
      determine the correct treatment of this complication and will achieve better
      outcomes.

PMID- 22476186
TI  - A family of three-dimensional 3d-4f and 4d-4f heterometallic coordination
      polymers based on mixed isonicotinate and 2-sulfobenzoate ligands: syntheses,
      structures and photoluminescent properties.
AB  - Hydrothermal reactions of isonicotinic acid (Hina), 2-sulfobenzoic acid
      (H(2)sba), d-block metal salts and lanthanide oxides/hydroxides yielded 17 three
      dimensional (3D) 3d-4f and 4d-4f heterometallic coordination polymers (HCPs).
      They are formulated as [LaAg(sba)(ina)(2)](n) (1),
      [Ln(2)Ag(2)(sba)(2)(ina)(4)(H(2)O)(2)](n) [Ln = Pr (2), Nd (3), Sm (4), Eu (5),
      Gd (6), Tb (7), Dy (8), Ho (9), Er (10)] and
      [Ln(2)Cu(2)(sba)(2)(ina)(4)(H(2)O)(2)](n) [Ln = La (11), Pr (12), Nd (13), Sm
      (14), Eu (15), Gd (16), Tb (17)]. Their structures were characterized by single
      crystal X-ray diffraction, powder X-ray diffraction (XRD), infrared (IR)
      spectroscopy, elemental analysis (EA), and thermogravimetric analysis (TGA). It
      reveals that they represent two structural types of 3D HCPs. Furthermore, the
      investigations of their solid-state photoluminescent (PL) property demonstrate
      the extraordinary emission behaviors. HCP 1(La-Ag) exhibits tunable blue-to-green
      PL emissions by variation of excitation light. HCPs 6(Gd-Ag), 11(La-Cu), 12(Pr
      Cu) and 16(Gd-Cu) show d(10)-metal-based ligand-to-metal charge transfer (LMCT)
      or metal-to-ligand charge transfer (MLCT) emissions. HCPs 3(Nd-Ag), 4(Sm-Ag),
      5(Eu-Ag), 7(Tb-Ag), 8(Dy-Ag), 13(Nd-Cu), 14(Sm-Cu), 15(Eu-Cu) and 17(Tb-Cu)
      display characteristic PL emissions of the corresponding Ln(III) ions, while both
      d(10)-metal-based and 4f-metal-centered emissions are observed in the emission
      spectra of 4(Sm-Ag), 8(Dy-Ag), 14(Sm-Cu) and 17(Tb-Cu).

PMID- 22476187
TI  - Pediatric genitourinary tumors.
AB  - PURPOSE OF REVIEW: We will review the 2010/2011 literature on pediatric
      genitourinary tumors and highlight the most significant publications. RECENT
      FINDINGS: New techniques such as gene expression profiling, PET, and nephron
      sparing surgery are being incorporated into contemporary treatments for pediatric
      patients with genitourinary tumors. Biologic markers are increasingly being used
      to help with risk stratification of patients and to identify new targets for
      therapy. WT1 mutation and 11p15 loss of heterozygosity have been associated with
      relapse in very low-risk Wilms tumors treated with surgery alone and may help
      reduce the use of chemotherapy in some children. Meta-analysis of data on the use
      of high-dose chemotherapy with autologous hematopoietic stem cell rescue in
      patients with relapsed Wilms tumor and rhabdomyosarcoma suggests that some
      patients may benefit more from conventional salvage chemotherapy. New agents are
      needed for patients with high-risk and relapsed disease to improve outcomes.
      SUMMARY: In general, the prognosis for patients with pediatric genitourinary
      tumors is favorable. Further understanding of the biology in these tumors is
      helping to determine risk stratification, treatment strategies, and candidates
      for new drug development.

PMID- 22476188
TI  - Targeting the DNA damage response in oncology:  past, present and future
      perspectives.
AB  - PURPOSE OF REVIEW: The success of poly(ADP-ribose) polymerase inhibition in BRCA1
      or BRCA2 deficient tumors as an anticancer strategy provided proof-of-concept for
      a synthetic lethality approach in oncology. There is therefore now active
      interest in expanding this approach to include other agents targeting the DNA
      damage response (DDR). We review lessons learnt from the development of
      inhibitors against DNA damage response mechanisms and envision the future of DNA
      repair inhibition in oncology. RECENT FINDINGS: Preclinical synthetic lethality
      screens may potentially identify the best combinations of DNA-damaging drugs with
      inhibitors of DNA repair and the DDR or two agents acting within the DDR. Efforts
      are currently being made to establish robust and cost-effective assays that may
      be implemented within appropriate time-scales in parallel with future clinical
      studies. Detection of relevant mutations in a high-throughput manner, such as
      with next-generation sequencing for genes implicated in homologous recombination,
      including BRCA1, BRCA2, and ataxia telangiectasia mutated is anticipated. Novel
      approaches targeting the DDR are currently being evaluated and inhibitors of ATM,
      RAD51 and DNA-dependent protein kinase are now in early drug discovery and
      development. SUMMARY: There remains great enthusiasm in oncology practice for
      pursuing the strategy of synthetic lethality. The future development of antitumor
      agents targeting the DDR should include detailed correlative biomarker work
      within early phase clinical studies wherever possible, with clear attempts to
      identify doses at which robust target modulation is observed.

PMID- 22476189
TI  - Early palliative care for patients with metastatic cancer.
AB  - PURPOSE OF REVIEW: At present, clinicians and healthcare providers are
      increasingly urged to advance the provision of state-of-the-art palliative care
      for patients with incurable cancer. This review provides an overview about the
      recent findings and practical suggestions. RECENT FINDINGS: In the last decade,
      the awareness about the logistic and personal resources needed to meet the
      somatic and psychological needs of patients with progressive and life-threatening
      diseases has increased and in parallel, palliative care concepts and expertise
      have evolved substantially. Care concepts for patients with metastatic cancer
      emphasized the potential of interdisciplinary care. For example, in 2010, a
      randomized trial reported a benefit for patients with lung cancer who received
      early palliative care in addition to routine care. It is discussed that this was
      because of increased quality of life and detailed exploration of patient
      preferences. SUMMARY: Patients, families and physicians benefit from shared care
      concepts of oncology and specialized palliative care. Although this concept is
      already becoming increasingly implemented in tertiary (comprehensive cancer-)
      care settings, the potential of this approach should be explored for other
      clinical settings such as office-based oncology.

PMID- 22476190
TI  - Supportive care in cancer unit at the National Cancer Institute of Milan: a new
      integrated model of medicine in oncology.
AB  - PURPOSE OF REVIEW: To present the model of the Supportive Care in Cancer Unit
      (SCCU) of the National Cancer Institute (NCI) of Milan. RECENT FINDINGS: In the
      last few years, there has been a debate on different models of integration of
      palliative care in oncology, on early palliative care, supportive care,
      supportive and palliative care, continuous care, end-of life care and pain
      management in the trajectory of cancer. SUMMARY: The aims of the SCCU of the NCI
      of Milan are mainly four: to collaborate with the individual specialists of NCI
      through integrated and ancillary activities while implementing a supportive
      therapy to treat the side effects, toxicities of oncological therapies, and
      comorbidities in the patients from the time of diagnosis and throughout the
      oncology treatment period; to assess all patients' needs through Italian
      validated versions of assessment tools, in order to ensure early care of the
      patient in a holistic approach; to support family members, survivors and
      healthcare professionals; and to promote research (pharmacological and non
      pharmacological) and educational programs.Our integrated model of medicine in
      oncology, which we define 'supportive care', is part of the clinical history of
      the patients, from the time of diagnosis and during oncological treatments, to
      facilitate their psychological well being and improve adherence to treatment
      protocols.

PMID- 22476191
TI  - Predictive factors for poor prognosis febrile neutropenia.
AB  - PURPOSE OF REVIEW: Most patients with chemotherapy-induced febrile neutropenia
      recover rapidly without serious complications. However, it still remains a life
      threatening treatment-related toxicity, and is associated with dose reductions
      and delays of chemotherapeutic agents that may compromise treatment outcomes.
      Recent developments of risk stratification enabled early discharge with oral
      antibiotics for low-risk patients. However, even in low-risk patients, medical
      complications including bacteremia could happen. The authors reviewed recent
      literature to provide an update on research regarding predictive factors for poor
      prognosis in patients with febrile neutropenia. RECENT FINDINGS: Various
      prognostic factors have been suggested with controversies. Hematological
      parameters, prophylactic measurements and patient-specific risk factors showed
      inconsistent results. MASCC risk-index score, which was originally developed to
      identify low-risk patients, in turn showed that the lower the MASCC score, the
      poorer the prognosis of febrile neutropenia, with very low levels (<15), the rate
      of complications was high. Patients with severe sepsis and septic shock commonly
      had procalcitonin concentration above 2.0 ng/ml, and this level should be
      considered at high risk of poor prognosis. SUMMARY: Lower MASCC score and higher
      procalcitonin concentration can predict poor outcomes in febrile neutropenia.
      More research is required with regard to the other factors showing controversies.

PMID- 22476192
TI  - The confusion around neuroendocrine tumors.

PMID- 22476193
TI  - Management of highly emetogenic chemotherapy.
AB  - PURPOSE OF REVIEW: This review updates the clinical data on antiemetic therapy
      for chemotherapy classified as highly emetogenic. RECENT FINDINGS: A meta
      analysis demonstrated that palonosetron was superior to other 5
      hydroxytryptamine3 (5-HT3) receptor antagonists at least in the absence of
      aprepitant. Two major guideline groups have reclassified all chemotherapy that
      contains cyclophosphamide and an anthracycline as 'highly emetogenic'. Although
      recommended prophylaxis for drugs in that category includes aprepitant, phase II
      studies with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and
      doxorubicin, bleomycin, vincristine and dacarbazine (ABVD) demonstrated that
      single agent palonosetron alone provided control of emesis over 85% of patients.
      A randomized phase III trial of olanzapine versus aprepitant found that the
      control of emesis was similar and nausea was significantly better controlled with
      olanzapine. Two studies showed that there is no impact of the moderate cytochrome
      P450 3A4 (CYP3A4) inhibitor aprepitant on the pharmacokinetics of
      cyclophosphamide. Surveys in the United States and Europe demonstrated that
      antiemetic prescribing practices often do not adhere to guidelines even for
      highly emetogenic chemotherapy. SUMMARY: The major guideline groups recommend a
      combination of a 5-HT3 receptor antagonist, dexamethasone and aprepitant ('triple
      therapy') for treatment categorized as highly emetogenic. Recent data suggest
      that, although classified as highly emetogenic, palonosetron may provide very
      good control of emesis for CHOP and ABVD. Guidelines have not made firm
      recommendations for highly emetogenic chemotherapy administered over several days
      or stem cell transplant preparative regimens due to the lack of published
      randomized trials. Although well tolerated and effective, many patients receive
      suboptimal antiemetic therapy that includes aprepitant.

PMID- 22476194
TI  - Increased host aggression as an induced defense against slave-making ants.
AB  - Slave-making ants reduce the fitness of surrounding host colonies through regular
      raids, causing the loss of brood and frequently queen and worker death.
      Consequently, hosts developed defenses against slave raids such as specific
      recognition and aggression toward social parasites, and indeed, we show that host
      ants react more aggressively toward slavemakers than toward nonparasitic
      competitors. Permanent behavioral defenses can be costly, and if social parasite
      impact varies in time and space, inducible defenses, which are only expressed
      after slavemaker detection, can be adaptive. We demonstrate for the first time an
      induced defense against slave-making ants: Cues from the slavemaker
      Protomognathus americanus caused an unspecific but long-lasting behavioral
      response in Temnothorax host ants. A 5-min within-nest encounter with a dead
      slavemaker raised the aggression level in T. longispinosus host colonies.
      Contrarily, encounters with nonparasitic competitors did not elicit aggressive
      responses toward non-nestmates. Increased aggression can be adaptive if a
      slavemaker encounter reliably indicates a forthcoming attack and if aggression
      increases postraid survival. Host aggression was elevated over 3 days, showing
      the ability of host ants to remember parasite encounters. The response
      disappeared after 2 weeks, possibly because by then the benefits of increased
      aggression counterbalance potential costs associated with it.

PMID- 22476195
TI  - Neuroendocrine tumours of the ampulla of Vater: clinico-pathological features,
      surgical approach and assessment of prognosis.
AB  - BACKGROUND/AIMS: Neuroendocrine tumours occur very rarely in the ampulla of Vater
      and their clinical behaviour is unknown. The aim of this study is to assess the
      clinico-pathological features, surgical approach and prognosis of these patients.
      METHODS: Six patients with neuroendocrine tumours of the ampulla of Vater treated
      with curative intent surgery at a single centre were retrospectively analysed. A
      univariate analysis of potential prognostic factors was also performed (data
      provided from the present study and literature review). RESULTS:
      Pancreaticoduodenectomy was curative in all the patients. Overall and disease
      free survival rates were significantly better for G1/G2 tumours (p = 0.006 and p
      = 0.004, respectively). Although frequent, lymph node metastases did not
      influenced both overall (p = 0.760) and disease-free survival rates (p = 0.745).
      No significant differences of survival were observed in patients with ENETS stage
      I/II disease, as compared to ENETS stage III disease (p = 0.169 and p = 0.137,
      respectively). No differences were observed according to UICC staging system (p =
      0.073 and p = 0.177, respectively). Tumours that are less than 2 cm or limited to
      the ampulla appear to have a better prognosis. CONCLUSION: The WHO 2010
      classification appear to accurately predict patient prognosis, while the ENETS or
      UICC staging systems have a limited value (especially in regard to lymph node
      metastases). Radical surgery (i.e. pancreaticoduodenectomy with lymphadenectomy)
      should be the standard approach in most patients with NET of the ampulla of Vater
      because this procedure removes all the potential tumour-bearing tissue.

PMID- 22476198
TI  - The Emergence of Two Functions for Spatial Devices in Nicaraguan Sign Language.
AB  - The emergence of a new sign language since the late 1970s in Nicaragua enables us
      to capture the effects of successive cohorts of learners on an emerging grammar
      and to observe how elements are reshaped from one form and function to another.
      Here we document the contrastive use of a device that has been found to be
      central to the grammars of sign languages: the spatial modulation of signs. In
      Nicaraguan Sign Language, this device has two primary functions: expressing the
      participants of events (that is, indicating who), and describing locations and
      orientations of referents (that is, indicating where). We ask whether the two
      uses reduce to a single construction type, or if the more abstract who
      construction derived from the more iconic and concrete where construction. We
      compare the first two successive cohorts of deaf signers to acquire the language
      in its first decade. We find that as learners created new constructions to meet
      the new functions, they did not simply apply an already developed form more
      broadly, nor did they develop the more abstract application from the more iconic
      one. Instead, the more abstract who construction appears to have conventionalized
      first. Thus, the forms either emerged independently, or split very early in the
      1980s, before either had developed as a consistently applied form.

PMID- 22476196
TI  - An anti-diabetes agent protects the mouse brain from defective insulin signaling
      caused by Alzheimer's disease- associated Abeta oligomers.
AB  - Defective brain insulin signaling has been suggested to contribute to the
      cognitive deficits in patients with Alzheimer's disease (AD). Although a
      connection between AD and diabetes has been suggested, a major unknown is the
      mechanism(s) by which insulin resistance in the brain arises in individuals with
      AD. Here, we show that serine phosphorylation of IRS-1 (IRS-1pSer) is common to
      both diseases. Brain tissue from humans with AD had elevated levels of IRS-1pSer
      and activated JNK, analogous to what occurs in peripheral tissue in patients with
      diabetes. We found that amyloid-beta peptide (Abeta) oligomers, synaptotoxins
      that accumulate in the brains of AD patients, activated the JNK/TNF-alpha
      pathway, induced IRS-1 phosphorylation at multiple serine residues, and inhibited
      physiological IRS-1pTyr in mature cultured hippocampal neurons. Impaired IRS-1
      signaling was also present in the hippocampi of Tg mice with a brain condition
      that models AD. Importantly, intracerebroventricular injection of Abeta oligomers
      triggered hippocampal IRS-1pSer and JNK activation in cynomolgus monkeys. The
      oligomer-induced neuronal pathologies observed in vitro, including impaired
      axonal transport, were prevented by exposure to exendin-4 (exenatide), an anti
      diabetes agent. In Tg mice, exendin-4 decreased levels of hippocampal IRS-1pSer
      and activated JNK and improved behavioral measures of cognition. By establishing
      molecular links between the dysregulated insulin signaling in AD and diabetes,
      our results open avenues for the investigation of new therapeutics in AD.

PMID- 22476199
TI  - Widening the Lens on Language Learning: Language Creation in Deaf Children and
      Adults in Nicaragua: Commentary on Senghas.

PMID- 22476197
TI  - Demonstrated brain insulin resistance in Alzheimer's disease patients is
      associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline.
AB  - While a potential causal factor in Alzheimer's disease (AD), brain insulin
      resistance has not been demonstrated directly in that disorder. We provide such a
      demonstration here by showing that the hippocampal formation (HF) and, to a
      lesser degree, the cerebellar cortex in AD cases without diabetes exhibit
      markedly reduced responses to insulin signaling in the IR->IRS-1->PI3K signaling
      pathway with greatly reduced responses to IGF-1 in the IGF-1R->IRS-2->PI3K
      signaling pathway. Reduced insulin responses were maximal at the level of IRS-1
      and were consistently associated with basal elevations in IRS-1 phosphorylated at
      serine 616 (IRS-1 pS616) and IRS-1 pS636/639. In the HF, these candidate
      biomarkers of brain insulin resistance increased commonly and progressively from
      normal cases to mild cognitively impaired cases to AD cases regardless of
      diabetes or APOE epsilon4 status. Levels of IRS-1 pS616 and IRS-1 pS636/639 and
      their activated kinases correlated positively with those of oligomeric Abeta
      plaques and were negatively associated with episodic and working memory, even
      after adjusting for Abeta plaques, neurofibrillary tangles, and APOE epsilon4.
      Brain insulin resistance thus appears to be an early and common feature of AD, a
      phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1
      dysfunction potentially triggered by Abeta oligomers and yet promoting cognitive
      decline independent of classic AD pathology.

PMID- 22476200
TI  - Smoking among chronically homeless adults: prevalence and correlates.
AB  - OBJECTIVE: Cigarette smoking is one of the leading preventable causes of death,
      and adults who are chronically homeless have among the highest death rates. This
      study examined the prevalence and correlates of smoking in this population.
      METHODS: Data were analyzed for 754 chronically homeless adults who were
      receiving mental health, primary care, and supported housing services at 11 U.S.
      sites in a federal initiative, the Collaborative Initiative to Help End Chronic
      Homelessness. The prevalence of current smoking (past three months),
      sociodemographic and clinical correlates of smoking, and change in smoking status
      (nonsmoker, self-limiting smoker, or regular smoker) over a one-year period were
      examined by use of stepwise multinomial regression analysis. RESULTS: Overall,
      80% of the 754 chronically homeless adults reported current cigarette smoking;
      48% of the smokers reported trying to limit their smoking, and 75% of the smokers
      had discussed smoking with a health care professional. No significant overall
      change in smoking status was found during the study year; however, change in
      alcohol and drug use was associated with change in smoking status in the same
      direction. Having a diagnosis of posttraumatic stress disorder and reducing
      alcohol use predicted quitting or limiting smoking. CONCLUSIONS: A large majority
      of chronically homeless adults reported being current smokers. Smoking cessation
      interventions, integrated with alcohol and drug treatment, that target this
      population are needed.

PMID- 22476201
TI  - Cross-regulations among NRFs and KEAP1 and effects of their silencing on arsenic
      induced antioxidant response and cytotoxicity in human keratinocytes.
AB  - BACKGROUND: Nuclear factor E2-related factors (NRFs), including NRF2 and NRF1,
      play critical roles in mediating the cellular adaptive response to oxidative
      stress. Human exposure to inorganic arsenic, a potent oxidative stressor, causes
      various dermal disorders, including hyperkeratosis and skin cancer. OBJECTIVE: We
      investigated the cross-regulations among NRF2, NRF1, and KEAP1, a cullin-3
      adapter protein that allows NRF2 to be ubiquinated and degraded by the proteasome
      complex, in arsenic-induced antioxidant responses. RESULTS: In human keratinocyte
      HaCaT cells, selective knockdown (KD) of NRF2 by lentiviral short hairpin RNAs
      (shRNAs) significantly reduced the expression of many antioxidant enzymes and
      sensitized the cells to acute cytotoxicity of inorganic arsenite (iAs(3+)). In
      contrast, silencing KEAP1 led to a dramatic resistance to iAs(3+)-induced
      apoptosis. Pretreatment of HaCaT cells with NRF2 activators, such as tert
      butylhydroquinone, protects the cells against acute iAs(3+) toxicity in an NRF2
      dependent fashion. Consistent with the negative regulatory role of KEAP1 in NRF2
      activation, KEAP1-KD cells exhibited enhanced transcriptional activity of NRF2
      under nonstressed conditions. However, deficiency in KEAP1 did not facilitate
      induction of NRF2-target genes by iAs(3+). In addition, NRF2 silencing reduced
      the expression of KEAP1 at transcription and protein levels but increased the
      protein expression of NRF1 under the iAs(3+)-exposed condition. In contrast,
      silencing KEAP1 augmented protein accumulation of NRF2 under basal and iAs3+
      exposed conditions, whereas the iAs(3+)-induced protein accumulation of NRF1 was
      attenuated in KEAP1-KD cells. CONCLUSIONS: Our studies suggest that NRF2, KEAP1,
      and NRF1 are coordinately involved in the regulation of the cellular adaptive
      response to iAs(3+)-induced oxidative stress.

PMID- 22476202
TI  - Using clinically approved cyclophosphamide regimens to control the humoral immune
      response to oncolytic viruses.
AB  - Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies
      whose titers increase progressively with each exposure, resulting in faster virus
      inactivation and further reductions in efficacy with each successive dose. A
      single dose of cyclophosphamide (CPA) at 370 mg m(-2) was not sufficient to
      control the primary antiviral immune responses in mice, squirrel monkeys and
      humans. We therefore tested clinically approved multidose CPA regimens, which are
      known to kill proliferating lymphocytes, to determine if more intensive CPA
      therapy can more effectively suppress antiviral antibody responses during
      virotherapy. In virus-susceptible mice, primary antibody responses to
      intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular
      stomatitis virus (VSV) were partially or completely suppressed, respectively, by
      oral (1 mg * 8 days) or systemic (3 mg * 4 days) CPA regimens initiated 1 day
      before virus. When MV- or VSV-immune mice were re-challenged with the respective
      viruses and concurrently treated with four daily systemic doses of CPA, their
      anamnestic antibody responses were completely suppressed and antiviral antibody
      titers fell significantly below pre-booster levels. We conclude that the CPA
      regimen of four daily doses at 370 mg m(-2) should be evaluated clinically with
      i.v. virotherapy to control the antiviral antibody response and facilitate
      effective repeat dosing.

PMID- 22476203
TI  - Cotton leaf curl Multan betasatellite as a plant gene delivery vector trans
      activated by taxonomically diverse geminiviruses.
AB  - Cotton leaf curl Multan betasatellite (CLCuMB) replicates in tobacco, tomato and
      datura plants in the presence of the helper viruses tomato leaf curl virus
      Australia, Iranian isolates of tomato yellow leaf curl virus, tomato leaf curl
      Karnataka virus, and beet severe curly top virus (BSCTV). Infectious recombinant
      CLCuMB constructs were made in which segments of either the CaMV 35S or the
      petunia ChsA promoter replaced the CLCuMB betaC1 ORF, and these were designated
      pBinbetaDeltaC1-35S and pBinbetaDeltaC1-ChsA, respectively. Inoculation of
      tobacco plants containing a functional 35S-GUS transgene with pBinbetaDeltaC1
      35S, and normal petunia plants with pBinbetaDeltaC1-ChsA, in the presence of
      helper viruses resulted in silencing of GUS and ChsA activities in transgenic
      tobacco and non-transgenic petunia plants, respectively. Replication of CLCuMB
      with different geminiviruses, especially BSCTV, a curtovirus with a broad host
      range, makes it a valuable gene delivery vector to the large number of host plant
      species of geminiviruses that support CLCuMB.

PMID- 22476204
TI  - Dehydration at admission increased the need for dialysis in hemolytic uremic
      syndrome children.
AB  - BACKGROUND: Oligoanuric forms of postdiarrheal hemolytic uremic syndrome (D+ HUS)
      usually have more severe acute stage and higher risk of chronic sequelae than
      nonoligoanuric forms. During the diarrheal phase, gastrointestinal losses could
      lead to dehydration with pre-renal injury enhancing the risk of oligoanuric D+
      HUS. Furthermore, it had been shown that intravenous volume expansion during the
      prodromal phase could decrease the frequency of oligoanuric renal failure. Thus,
      we performed this retrospective study to determine whether dehydration on
      admission is associated with increased need for dialysis in D+ HUS patients. CASE
      DIAGNOSIS/TREATMENT: Data from 137 children was reviewed, which were divided into
      two groups according to their hydration status at admission: normohydrated (n =
      86) and dehydrated (n = 51). Laboratory parameters of the dehydrated patients
      reflected expected deteriorations (higher urea, higher hematocrit and lower
      sodium, bicarbonate, and pH) than normohydrated ones. Likewise, the dehydrated
      group had a higher rate of vomiting and need for dialysis (70.6 versus 40.7 %, p
      = 0.0007). CONCLUSIONS: Our data suggests that dehydration at hospital admission
      might represent a concomitant factor aggravating the intrinsic renal disease in
      D+ HUS patients increasing the need for dialysis. Therefore, the early
      recognition of patients at risk of D+ HUS is encouraged to guarantee a well
      hydrated status.

PMID- 22476205
TI  - Quality of life of patients with rheumatoid arthritis in Argentina: reliability,
      validity, and sensitivity to change of a Spanish version of the Rheumatoid
      Arthritis Quality of Life questionnaire.
AB  - The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is the first needs
      based instrument specifically designed to measure quality of life (QoL) of
      patients with rheumatoid arthritis (RA). The aims of our study were to develop an
      Argentinean version of the RAQoL and to determine its reproducibility, validity,
      and sensitivity to change in patients with RA. Translation process was performed
      according to internationally accepted methodology. Internal consistency and test
      retest reliability were calculated. Criterion and construct validity were
      assessed by comparing the RAQoL with parameters of disease activity, the Health
      Assessment Questionnaire (HAQ), and the Medical Outcomes Study 36-item health
      survey (SF-36) questionnaire. Sensitivity to change was measured at 6-12 months
      using standardized response mean (SRM). The minimal important change was defined
      as a change of 1 or 1.96 times the standard error of measurement. A total of 97
      patients with RA were included. Cronbach's alpha was 0.93, and test-retest
      reliability was 0.95. The RAQoL showed moderate to strong correlation with
      parameters of disease activity, the HAQ, and the SF-36. Functional status was the
      main determinant of patients' level of QoL. The SRM of the RAQoL was 0.24.
      Agreement between 20 % improvement in RAQoL and ACR20 response was moderate.
      Minimal important change was 2.2 (1 SEM) or 4.3 (1.96 SEM). The Argentinean
      version of the RAQoL is the first Spanish translation of this questionnaire. Our
      findings show it to be valid, reliable, and sensitive to changes in RA clinical
      status.

PMID- 22476207
TI  - The first TDDFT and MCD studies of free base triarylcorroles: a closer look into
      solvent-dependent UV-visible absorption.
AB  - Absorption spectra of several free base triarylcorroles were investigated by MCD
      spectroscopy. The MCD spectra exhibit unusual sign-reverse (positive-to-negative
      intensities in ascending energy) features in the Soret- and Q-type band regions,
      suggesting a rare DeltaHOMO < DeltaLUMO relationship between pi and pi* MOs in
      the corrole core.

PMID- 22476206
TI  - Invasive fungal infection in Chinese patients with systemic lupus erythematosus.
AB  - Invasive fungal infection (IFI) can be a lethal complication in systemic lupus
      erythematosus (SLE). The aim of this study was to determine the characteristics
      of hospitalized SLE patients with IFI, and identify the risk factors compared to
      SLE with other major infections or those with active disease alone. Data from 18
      SLE in-patients with IFI at Shanghai Renji Hospital between January 2007 and
      January 2011 were collected by chart review. SLE patients with either active
      Mycobacterium tuberculosis (n = 19) or other bacterial infections (n = 17), or
      active SLE (n = 54) in the same period acted as controls. SLE in-patients with
      IFI (n = 11) from January 2002 to December 2006 was considered as a historical
      control group. The most frequent pathogens of SLE-IFI was Cryptococcus neoformans
      (n = 9, 50.0 %), followed by Aspergillus and Candida (both n = 3, 16.7 %). The
      infection sites included lung (n = 8, 44.4 %), central nervous system (n = 8,
      44.4 %), and disseminated IFI (n = 2, 11.1 %). Three patients (16.7 %) died from
      IFI. Compared with other major infections, IFI patients were younger, with
      shorter SLE disease duration, lower C-reactive protein response, higher
      corticosteroids, and antibiotics exposure. Compared with active SLE, IFI patients
      had elevated alanine transaminase level, higher corticosteroids and antibiotics
      exposure. In multivariate analysis, the only significant risk factors for IFI
      were maximum prednisolone exposure >=45 mg/day prior to infection or flare within
      3 months (OR = 10.284, 95 %CI (2.877, 36.836)). Compared with the historical SLE
      IFI patients, the short-term survival improved over time (63.6 % versus 83.3 %).
      SLE-IFI is a unique entity that characterized by certain aforementioned
      parameters compared with other major infections or disease flare in SLE. Familiar
      with the disease pattern along with appropriate antifungal treatment may lead to
      a better outcome in SLE-IFI patients.

PMID- 22476208
TI  - Stereoselective synthesis of functionalised carbocyclic amides: construction of
      the syn-(4aS,10bS)-phenanthridone skeleton.
AB  - A new synthetic approach has been developed for the preparation of 7
      deoxypancratistatin analogues bearing a syn-(4aS,10bS)-phenanthridone ring
      junction. A one-pot tandem process involving a substrate-directed Overman
      rearrangement and ring closing metathesis reaction was developed for the
      stereoselective synthesis of a carbocyclic allylic trichloroacetamide. Conversion
      to a 6-bromopiperonyl amide, followed by a Heck reaction generated a homoallylic
      alcohol and completed the syn-(4aS,10bS)-phenanthridone carbon skeleton.
      Stereoselective epoxidation and dihydroxylation of the syn-(4aS,10bS)
      phenanthridone framework was then investigated leading to the preparation of new
      analogues of 7-deoxypancratistatin.

PMID- 22476209
TI  - Prevalence, incidence, and stimulant use of attention-deficit hyperactivity
      disorder in Taiwan, 1996-2005: a national population-based study.
AB  - PURPOSE: We used National Health Insurance (NHI) database to examine the
      prevalence, incidence, and stimulant use of attention-deficit hyperactivity
      disorder (ADHD) diagnosis in Taiwan. METHODS: The National Health Research
      Institute provided a database of 10,00,000 random subjects for study. A
      population-based random sample of 372,642 patients aged younger than 18 was
      obtained as a dynamic cohort. Those study subjects who had at least one service
      claim from 1996 to 2005, with a principal diagnosis of ADHD, were identified.
      RESULTS: The cumulative prevalence of ADHD diagnosis increased from 0.06 to 1.64
      % from 1996 to 2005. The annual incidence of ADHD diagnosis increased from 0.02
      to 0.34 % from 1997 to 2005. The highest incidence rates of ADHD diagnosis for
      both males and females were in the 6- to 11-year age group. Higher incidence was
      detected in males (HR 3.76, 95 % CI 3.48-4.07), those who lived in northern
      region (HR 1.35, 95 % CI 1.07-1.71) and urban area (HR 1.53, 95 % CI 1.40-1.66).
      The percentage of stimulant use in children with ADHD diagnosis increased from
      39.6 to 54.0 % from 1997 to 2005. CONCLUSIONS: Our findings suggest increases in
      the prevalence and incidence rates of ADHD diagnosis in Taiwan, which was in line
      with those studies of Western countries. However, the prevalence of ADHD
      diagnosis in the NHI program was still much lower than in the community studies.
      The percentage of stimulant use in children with ADHD diagnosis also has an
      increasing trend, which warrants further study.

PMID- 22476210
TI  - Gender inequality and structural violence among depressed women in South India.
AB  - PURPOSE: While exploring experiences of psychological distress among psychiatric
      outpatients in Southern India, we set out to further understand interpersonal and
      socio-cultural factors that are associated with depressive symptoms. METHODS:
      Using a grounded theory framework, we thematically coded narrative accounts of
      the women who sought treatment at the psychiatric clinic. In addition, we
      included author notes from participant observation and field work experiences in
      the South Indian psychiatric clinic. RESULTS: Of the 32 women who participated in
      the study, 75 % qualified for a diagnosis of a current major depressive episode.
      Depressive symptoms were associated with experiences of domestic violence and, in
      Farmer's terms, structural violence. Although only a partial response to gender
      based suffering, allopathic psychiatric treatment seemed the best available means
      of coping with their circumstances. CONCLUSION: The paper moves beyond a
      medicalized model of disease and behavior to explore social and contextual
      factors that enabled these women to brave additional stigmas surrounding
      psychiatric treatment and seek a better outcome for themselves. It concludes by
      discussing the need for a multi-layered approach to addressing the suffering that
      women in South India experience.

PMID- 22476211
TI  - [A 76-year-old female patient with deep venous thrombosis and cervical
      lymphadenopathy].
AB  - We report the case of a 76-year-old female patient presenting with deep venous
      thrombosis and upper cervical lymphadenopathy. A computed tomography (CT) scan
      showed multiple hepatic lesions with a high suspicion of metastatic disease from
      an unknown primary tumor. The differential diagnosis of lymphadenopathy and
      hepatic lesions includes malignant tumors and various infectious diseases. The
      diagnostic process, however, revealed lymph node tuberculosis with multiple
      hepatic granulomas despite a repeatedly negative interferon-gamma release assay.
      A combined antituberculosis therapy led to complete clinical remission.

PMID- 22476212
TI  - Queen reproductive state modulates pheromone production and queen-worker
      interactions in honeybees.
AB  - The mandibular glands of queen honeybees produce a pheromone that modulates many
      aspects of worker honeybee physiology and behavior and is critical for colony
      social organization. The exact chemical blend produced by the queen differs
      between virgin and mated, laying queens. Here, we investigate the role of mating
      and reproductive state on queen pheromone production and worker responses. Virgin
      queens, naturally mated queens, and queens instrumentally inseminated with either
      semen or saline were collected 2 days after mating or insemination. Naturally
      mated queens had the most activated ovaries and the most distinct chemical
      profile in their mandibular glands. Instrumentally inseminated queens were
      intermediate between virgins and naturally mated queens for both ovary activation
      and chemical profiles. There were no significant differences between semen- and
      saline-inseminated queens. Workers were preferentially attracted to the
      mandibular gland extracts from queens with significantly more activated ovaries.
      These studies suggest that the queen pheromone blend is modulated by the
      reproductive status of the queens, and workers can detect these subtle
      differences and are more responsive to queens with higher reproductive potential.
      Furthermore, it appears as if insemination substance does not strongly affect
      physiological characteristics of honeybee queens 2 days after insemination,
      suggesting that the insemination process or volume is responsible for stimulating
      these early postmating changes in honeybee queens.

PMID- 22476213
TI  - Total hip replacement in patients with history of illicit injecting drug use.
AB  - BACKGROUND: A history of illicit injecting drug use makes indication of total hip
      arthroplasty (THA) in patients with end stage hip osteoarthritis difficult, as
      the risk of infection with colonized strains is multiplied if the patient
      continues to inject or inhale illicit drugs. METHODS: A retrospective
      survivorship analysis of a consecutive series of 27 THA in patients with a
      history of illicit drug use was performed. Follow-up evaluation consisted of (1)
      a WOMAC score, (2) a standardized interview including queries on drug habits and
      eventual additional medico-surgical treatments of the affected hip, (3) a
      clinical examination in order to complete a Harris Hip Score, (4) radiological
      examination and (5) blood tests (blood sedimentation rates and C-reactive
      protein). Defined endpoints were death, implant revised or awaiting revision for
      deep infection or any other reason and lost to follow-up or follow-up after at
      least 2 years. RESULTS: Overall, 5- and 10-year implant survival rates with
      failure for any reason were 61 % (CI: 41;81) and 52.3 % (CI: 29;76) and for
      septic reasons 70.6 % (CI: 52;89) and 60.5 % (CI: 36;85), respectively. Even if
      at the time of THA all patients and respective health care professionals
      confirmed abstinence of illicit injecting drug use, five patients reported
      occasional use. Declared abstinence of less than 1 year before THA was associated
      with higher recurrence rates (p = 0.001) and both with higher septic failure
      rates (p = 0.023, p = 0.061). Positive serology for human deficiency virus did
      not increase implant failure rates. CONCLUSION: We use this unacceptable high
      failure rate as evidence when counseling patients and their health care
      professionals about the appropriate treatment of osteoarthritis in patients with
      a history of illicit drug use. Furthermore, we support the request of hair
      analysis for drugs documenting abstinence of at least 1 year before indicating
      THA.

PMID- 22476214
TI  - Vection can be induced in the absence of explicit motion stimuli.
AB  - The present study utilized two separate experiments to demonstrate that illusory
      self-motion (vection) can be induced/modulated by cognition. In the first
      experiment, two curved lines, which simulated road edges seen while driving at
      night, were employed. Although the lines induced adequate strength of forward
      vection, when one of the lines was horizontally reversed, vection was
      significantly reduced. In the second experiment, two static converging lines with
      moving characters, which simulated side edges of a straight road with a traffic
      sign, were utilized. The road sign moved only during the first 5 s. After the
      sign disappeared, only static lines or a blank screen were able to induce
      vection. These results suggested that vection was largely affected by cognitive
      factors and that vection could be induced by implicit motion stimuli.

PMID- 22476215
TI  - Active training paradigm for motor imagery BCI.
AB  - Brain-computer interface (BCI) allows the use of brain activities for people to
      directly communicate with the external world or to control external devices
      without participation of any peripheral nerves and muscles. Motor imagery is one
      of the most popular modes in the research field of brain-computer interface.
      Although motor imagery BCI has some advantages compared with other modes of BCI,
      such as asynchronization, it is necessary to require training sessions before
      using it. The performance of trained BCI system depends on the quality of
      training samples or the subject engagement. In order to improve training effect
      and decrease training time, we proposed a new paradigm where subjects
      participated in training more actively than in the traditional paradigm. In the
      traditional paradigm, a cue (to indicate what kind of motor imagery should be
      imagined during the current trial) is given to the subject at the beginning of a
      trial or during a trial, and this cue is also used as a label for this trial. It
      is usually assumed that labels for trials are accurate in the traditional
      paradigm, although subjects may not have performed the required or correct kind
      of motor imagery, and trials may thus be mislabeled. And then those mislabeled
      trials give rise to interference during model training. In our proposed paradigm,
      the subject is required to reconfirm the label and can correct the label when
      necessary. This active training paradigm may generate better training samples
      with fewer inconsistent labels because it overcomes mistakes when subject's motor
      imagination does not match the given cues. The experiments confirm that our
      proposed paradigm achieves better performance; the improvement is significant
      according to statistical analysis.

PMID- 22476216
TI  - Tissue characteristics during temporal summation of pressure-evoked pain.
AB  - Temporal summation due to repeated pain stimulation of deep somatic structures is
      facilitated in chronic musculoskeletal pain. In this study, the relation between
      repeated pressure-induced pain and stress/strain distribution within the deep
      tissue was evaluated to understand whether tissue characteristics may change
      during repeated stimulation. This information is important for interpret the pain
      evoked responses. The muscle pain intensity was recorded on a 10-cm visual
      analogue scale (VAS) during ten computer-controlled pressure stimulations (3-s
      interstimulus interval) at pain threshold intensity. The experimental data
      validated computer models describing the stress/strain time relationship in the
      deep tissue during pressure stimulation. VAS scores increased progressively with
      2.5 +/- 0.7 cm during the ten stimuli (P < 0.02) in contrast to the tissue
      indentation assessed by ultrasound, which was non-significantly changing leading
      to a mean of 3.4 +/- 0.4 mm. The principal stress peaked in the skin was reduced
      to 16 % in the underlying muscle tissue and not different during the ten stimuli.
      The peak principal strain in adipose tissue was 0.12; in muscle tissue, it was
      0.108 during the first stimulus and increased by 16 % in the tenth stimulus. In a
      model of a one-stimulus paradigm, it was found that a VAS increase of 2.5 cm
      required a 47 % increase in muscle strain. These findings show that the increase
      in muscle strain during repeated pressure stimulations is not sufficient to
      explain the VAS increase; the temporal summation of deep-tissue pain evoked by
      repetitive pressure stimulations is not likely to be fully explained by
      peripheral tissue changes.

PMID- 22476217
TI  - Spinal and cortical activity-dependent plasticity following learning of complex
      arm movements in humans.
AB  - Activity-dependent plasticity is a fundamental requirement for human motor
      learning, which takes place at several stages of the motor system and involves
      various mechanisms in neuronal circuitry. Here, we investigate parameters of
      cortical and spinal excitability before and immediately after a single session of
      locomotion-like arm training (LMT) or sequential visuo-motor learning (VMT). Both
      training paradigms focused especially on mainly activating the flexor carpi
      radialis muscle (FCR). The activity-dependent change in the excitability of FCR
      associated neurons was investigated using standard transcranial magnetic
      stimulation, including analysis of motor-evoked potentials (MEP) amplitude, short
      interval intracortical inhibition and intracortical facilitation (ICF).
      Furthermore, spinal plasticity was also assessed by means of homosynaptic FCR H
      reflex depression (HD). LMT decreased HD and ICF. In contrast, VMT had no
      significant effect on cortical and spinal parameters. There was a nonsignificant
      tendency of an increase in MEP amplitudes after both interventions. This implies
      that human locomotor-related learning involves spinal mechanisms. Despite the
      decreasing importance of quadrupedal coordination in the course of evolution,
      these changes in transsynaptic plasticity may reflect a persisting locomotor
      memory-encoding function in the spinal circuitry of the human upper extremities.
      Evaluating FCR HD might be helpful for the evaluation and development of
      locomotor rehabilitation strategies.

PMID- 22476219
TI  - Immunological complications beyond rejection after intestinal transplantation.
AB  - PURPOSE OF REVIEW: Intestinal transplantation (ITx) represents a major
      immunological challenge as the bidirectional exchange of donor's and recipient's
      immune cells delivers a graft highly chimeric and immunogenic. Therefore, there
      is a higher risk for immunological complications. It is important to understand
      the prevalence, natural history and mechanisms of other immunological
      complications, beyond rejection, to better understand the implications of ITx.
      RECENT FINDINGS: In recent studies, graft-versus-host disease (GVHD) holds a high
      mortality (43-70%). Apart from increasing or modifying immunosuppression, there
      are not other new therapies at this time. Inflammatory bowel disease (IBD) in
      solid organ transplant recipients has been estimated to be 10 times that of the
      general population. In the ITx recipient, it is not clear whether IBD is an
      autonomous disorder or a different phenotype of acute rejection. There are some
      studies suggesting that anti-tumour necrosis factor alpha (anti-TNFalpha) may
      have a role in preventing or treating rejection. According to recent studies, the
      incidence of autoimmune hemolytic anemia is 11% and a large proportion of these
      patients will respond to conventional therapy. SUMMARY: Rejection, GVHD, IBD-like
      disorder, autoimmune disorders and food allergies are among the more significant
      immunological complications after ITx. We need further studies to comprehend the
      risk factors and pathophysiology that will lead to better markers and innovative
      therapies that will impact survival.

PMID- 22476220
TI  - Antibody-mediated rejection after intestinal transplantation.
AB  - PURPOSE OF REVIEW: In spite of impressive improvements in short-term outcomes for
      intestine transplant recipients, late allograft loss continues to plague the
      field. Attention has mostly been focused on T-cell-mediated cellular mechanisms
      of allograft rejection to explain these losses; however, as in other forms of
      solid-organ transplantation, especially kidney and heart, antibody-mediated
      mechanisms of acute and chronic allograft injury are increasingly being
      implicated. In this review, the mechanisms of B-cell- and humoral-mediated
      allograft injury will be briefly discussed along with the limited evidence that
      exist for invoking antibody-mediated rejection (AMR) as important in intestine
      transplantation. RECENT FINDINGS: The presence of donor-specific antibody has
      been reported to increase the incidence and severity of intestine allograft
      rejection and to worsen the overall prognosis for graft and patient. C4d staining
      in intestine biopsies is unreliable, and currently it is not possible to diagnose
      AMR with certainty in intestine transplantation. Treatment of presumed AMR in
      intestine recipients is purely anecdotal at this time. SUMMARY: Further basic and
      clinical research needs to be conducted to more confidently diagnose and treat
      AMR in intestinal transplantation.

PMID- 22476218
TI  - A novel HSI2 mutation in Arabidopsis affects the PHD-like domain and leads to
      derepression of seed-specific gene expression.
AB  - Two related B3 domain transcriptional repressors, HSI2 (HIGH-LEVEL EXPRESSION OF
      SUGAR-INDUCIBLE GENE2)/VAL1 (VP1/ABI3-LIKE1) and HSL1 (HSI2-LIKE1)/VAL2, function
      redundantly to repress key transcriptional regulators of seed maturation genes in
      Arabidopsis thaliana seedlings. Using a forward genetic screen designed to
      isolate trans-acting mutants that affected expression of a transgene containing
      the glutathione S-transferase F8 promoter::luciferase (GSTF8::LUC) reporter, we
      identified a novel HSI2 mutant allele, hsi2-4, that exhibits constitutively
      elevated luciferase expression while expression of the endogenous GSTF8
      transcript remains unchanged. The hsi2-4 lesion was found to be a missense
      mutation that results in the substitution of a conserved cysteine within the
      plant homeodomain-like (PHD) motif of HSI2. Microarray analysis of hsi2-4 and
      hsi2-4 hsl1 mutants indicated that the HSI2 PHD-like domain functions non
      redundantly to repress a subset of seed maturation genes, including those that
      encode AGL15 (AGAMOUS-LIKE15), FUSCA3 (FUS3), cruciferins, cupin family proteins,
      late-embryogenesis abundant protein, oleosins, 2S albumins and other seed
      specific proteins in Arabidopsis seedlings. Many genes that are responsive to
      this mutation in the HSI2 PHD-like domain are enriched in histone H3
      trimethylation on lysine 27 residues (H3K27me3), a repressive epigenetic mark.
      Chromatin immunoprecipitation analysis showed that sequences of the GSTF8::LUC
      transgene are enriched in H3K27me3 in a HSI2 PHD domain-dependent manner. These
      results indicate that the transcriptional repression activity of the HSI2 PHD
      domain could be mediated, at least in part, by its participation in the
      deposition of H3K27me3 on the chromatin of specific target genes.

PMID- 22476221
TI  - Hepatitis C virus treatment and liver transplantation in the era of new antiviral
      therapies.
AB  - PURPOSE OF REVIEW: The new standard-of-care treatment for genotype 1 hepatitis C
      virus infection is a combination of PEG-interferon (PEG-IFN), ribavirin (RBV) and
      a protease inhibitor - telaprevir or boceprevir. As triple therapy is not yet
      approved for use in decompensated cirrhotics and liver transplant recipients, we
      examine the efficacy and safety of PEG-IFN, RBV and protease inhibitors in
      nontransplant populations to inform the current and future treatment paradigms
      for transplant candidates and recipients. RECENT FINDINGS: Protease inhibitor
      based triple therapy is more efficacious than PEG-IFN and RBV in nontransplant
      genotype 1 patients, so sustained virologic response rates are predicted to be
      higher in waitlisted candidates and transplant recipients treated with protease
      inhibitor-triple therapy. Because of the need to use a backbone of PEG-IFN and
      RBV, tolerability of therapy will remain a major challenge. Anemia, a well
      recognized side-effect with PEG-IFN and RBV, will be especially common with
      protease inhibitor-triple therapy. Both protease inhibitors can modify the levels
      of drugs metabolized by the CYP3A/4 pathway, and in posttransplant patients, the
      protease inhibitors increase the levels of cyclosporine and tacrolimus, with the
      magnitude of the drug-drug interactions varying with protease inhibitor and type
      of calcineurin inhibitor (CNI). SUMMARY: Given the complexities of treatment, it
      is best undertaken by experienced clinicians and only after a detailed discussion
      of risks-benefits with the patient. To maximize the benefit while minimizing
      risk, only Child-Turcott-Pugh A (CPT-A) cirrhotics should be considered for
      pretransplant protease inhibitor-triple therapy. For transplant recipients, very
      close monitoring and adjustment of CNI levels is critical during protease
      inhibitor-triple therapy. Cytopenias, especially anemia, will require aggressive
      management.

PMID- 22476222
TI  - Technical advances for abdominal wall closure after intestinal and multivisceral
      transplantation.
AB  - PURPOSE OF REVIEW: Abdominal wall closure after intestinal transplantation (ITX)
      or multivisceral transplantation (MVTX) is challenging because of the loss of
      abdominal domain and wall elasticity as a result of previous operations and donor
      to-recipient weight and height mismatch. RECENT FINDINGS: We report on abdominal
      wall closure management in 30 ITX and MVTX recipients. In 60% of patients (n =
      18), a primary abdominal closure (PAC) was achieved, in 40% (n = 12) a staged
      closure (SAC) was necessary. Patients with PAC had undergone less pretransplant
      operations and required less posttransplant relaparotomies. They were mainly ITX
      recipients or more abdominal domain because of a longer intestinal remnant. A
      literature review revealed different strategies to overcome a failed primary
      closure. They focus on graft reduction or an enlargement of the abdominal domain.
      The latter includes temporary coverage with prosthetic materials for SAC.
      Definite abdominal closure is achieved by skin only closure, or by using
      acellular dermal matrix, rotational flaps, rectus muscle fascia or abdominal wall
      grafts. SUMMARY: Abdominal wall reconstruction after ITX/MVTX is commonly
      demanded and can be conducted by different strategies. The technique should be
      easy to use in a timely manner and should prevent abdominal infections,
      intestinal fistulation, incisional hernias, and wound dehiscence.

PMID- 22476223
TI  - How can pathologists help to diagnose late complications in small bowel and
      multivisceral transplantation?
AB  - PURPOSE OF REVIEW: Intestinal transplantation (ITx) and multivisceral
      transplantation (MVTx) has evolved into a viable treatment option for short bowel
      syndrome and intestinal failure due to a variety of factors including improved
      immunosuppressive regimens, superior surgical and medical management, and
      enhanced posttransplant monitoring. RECENT FINDINGS: The transplant pathologist
      is a central member of the transplant team in all phases of solid organ
      transplantation and as such, plays an important role in the evaluation of early
      and late complications after ITx and MVTx. Central among the tools for the
      pathologist is the mucosal biopsy, used for discerning histopathological changes
      in the allograft. The principal complications seen in the late posttransplant
      phase are acute rejection, chronic rejection, infections, and a variety of other
      inflammatory conditions. In order to more precisely characterize these
      conditions, the transplant pathologist must also be able to utilize numerous
      other laboratory tests and panels of molecular biomarkers that serve as ancillary
      information to complement the biopsy impression. SUMMARY: Using this array of
      tools, the transplant pathologist is now able to provide rapid and precise
      information regarding the gastrointestinal (GI) transplant complications, a
      function that allows the clinical team to appropriately and successfully
      intervene and that helps contribute to the observed improvement in patient and
      graft survival.

PMID- 22476224
TI  - Cellular therapy and bioartificial approaches to liver replacement.
AB  - PURPOSE OF REVIEW: The success of liver transplantation has increased over the
      past 20 years due to improved immunosuppressive medications, surgical technique
      and donor-recipient selection. To date, the number of patients waiting for a
      liver transplant exceeds the number of transplants performed yearly by over a 2 :
      1 ratio. Despite efforts to expand the donor pool, mortality of patients waiting
      for a liver remains high due to the shortage of donor organs. Herein, we discuss
      options for liver replacement that are currently under development. RECENT
      FINDINGS: Extracorporeal bioactive liver perfusion devices were investigated in
      the late 1990s and preliminarily demonstrated safety but failed to show clinical
      efficacy. Current research is ongoing, but the focus has shifted to
      xenotransplantation of whole organs, organ engineering and cell transplantation.
      These new modalities are limited to small and large animal studies and each
      present unique advantages and limitations. SUMMARY: Discovery of new sources of
      organs or cells to replace a damaged liver may be the only long-term solution to
      provide definitive therapy to all patients who require transplantation. The past
      2 years have seen notable achievements in xenotransplantation, tissue engineering
      and cell transplantation. Though challenges remain, now identified, they may be
      readily solved.

PMID- 22476226
TI  - Development of a core set of performance measures for evaluating schizophrenia
      treatment services.
AB  - OBJECTIVE: The purpose of study was to identify a list of performance measures
      for schizophrenia treatment services and to assemble a multistakeholder group to
      reach consensus on a core list. METHODS: The study was conducted in two stages:
      first, a systematic review of the literature was conducted to identify a
      comprehensive list of measures; second, a consensus-building technique, the
      Delphi process, was used with participants from six groups of stakeholders:
      schizophrenia experts, mental health clinicians, mental health administrators,
      the payer (the Alberta Ministry of Health and Wellness), patients, and family
      members. Thirty stakeholders participated in three rounds of self-completed
      questionnaires. The degree of consensus achieved in the Delphi process was
      defined as the semi-interquartile range for each measure. RESULTS: Ninety-seven
      measures were identified in the literature review. The Delphi method reduced the
      list to 36 measures rated as essential. The measures address eight domains of
      service-level evaluation: acceptability, accessibility, appropriateness,
      competence, continuity, effectiveness, efficiency, and safety. Despite the
      diversity in backgrounds of the stakeholder groups, the Delphi technique was
      effective in moving participants' ratings toward consensus through successive
      questionnaire rounds. The resulting measures reflected the interests of all
      stakeholders. CONCLUSIONS: Several further steps are required before these
      measures are implemented and include working toward reliability and validity of
      specific measures, assessing the feasibility and cost-effectiveness of collecting
      the data, and finally, undertaking risk adjustment for outcome measures.

PMID- 22476225
TI  - Quality of life, risk assessment, and safety research in liver transplantation: 
      new frontiers in health services and outcomes research.
AB  - PURPOSE OF REVIEW: In this review, we briefly summarize three fruitful, emerging
      areas in liver transplantation research, quality of life; risk assessment; and
      patient safety. Our goal is to highlight recent findings in these areas, with a
      call for increased integration of social scientists and transplant clinicians to
      address how best to shape policy and improve outcomes. RECENT FINDINGS: After
      liver transplantation, recipients generally experience clinically significant,
      sustained improvement in their physical, social and emotional well being.
      However, a sizeable minority of patients do experience excess morbidity that may
      benefit from ongoing surveillance and/or intervention. There is growing body of
      research that describes risks associated with liver transplantation, which can be
      useful aids to better inform decision making by patients, clinicians, payers, and
      policy makers. In contrast, there has been a relative lack of empirical data on
      transplant patient safety vulnerabilities, placing the field of surgery in stark
      contrast to other high-risk industries, wherein such assessments inform
      continuous process improvement. SUMMARY: Health services and outcomes research
      has grown in importance in the liver transplantation literature, but several
      important questions remain unanswered that merit programmatic, interdisciplinary
      research.

PMID- 22476227
TI  - Ethnic differences in genetic predisposition to hypertension.
AB  - Recently, large-scale meta-analyses of genome-wide association (GWA) studies have
      identified a number of loci significantly associated with systolic and/or
      diastolic blood pressure (BP). Most of the GWA studies reported to date were
      conducted in populations of European descent. Given the appreciable ethnic
      differences in clinical presentation of hypertension, studies in non-European
      populations allow us to assess the relevance of the findings in Europeans to
      other ethnic groups and to potentially discover novel variants. Before the GWA
      scan era, the presence of racial or ethnic differences has been widely recognized
      for response to antihypertensive therapies, salt sensitivity and impact of
      obesity on developing hypertension. Despite a limited number of genetic loci that
      have been proven to show substantial ethnic differences, we can assume four
      possible genetic mechanisms--(1) absence of target variants in other ethnic
      groups; (2) presence of allelic heterogeneity; (3) difference in linkage
      disequilibrium structure; and (4) gene-gene and gene-environment interactions.
      Considering such a number of potential sources of heterogeneity, we should be
      cautious about claiming the presence of genuine ethnic differences in genetic
      susceptibility to BP-related traits or hypertension. Approximately a quarter of
      BP-associated loci that have been reported in four meta-analyses of GWA studies
      (i.e., 8 out of 34 loci) appear to be common across three ethnic groups-
      Europeans, east Asians and south Asians. 'Transethnic' BP meta-analysis will be
      useful not only for revealing novel susceptibility loci and pathophysiological
      pathways but also for facilitating the fine mapping of common causal variants.

PMID- 22476228
TI  - Association between genetic variants of the ADD1 and GNB3 genes and blood
      pressure response to the cold pressor test in a Chinese Han population: the
      GenSalt Study.
AB  - Genetic factors influence blood pressure (BP) response to the cold pressor test
      (CPT), which is a phenotype related to hypertension risk. We examined the
      association between variants of the alpha-adducin (ADD1) and guanine nucleotide
      binding protein (G protein) beta-polypeptide 3 (GNB3) genes and BP response to
      the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology
      Network of Salt Sensitivity completed the CPT. The area under the curve (AUC)
      above the baseline BP during the CPT was used to measure the BP response. Twelve
      single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected
      and genotyped. Both single-marker and haplotype association analyses were
      conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the
      ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated
      with the BP response to CPT, even after adjusting for multiple testing. For the
      ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic
      BP (SBP) reactivity (P<0.0001) and faster BP recovery (P=0.0003). The TT genotype
      of rs3775067 was associated with slower SBP recovery (P=0.004). For the GNB3
      gene, the C allele of SNP rs4963516 was associated with faster diastolic BP
      recovery (P=0.002) and smaller overall AUC (P=0.003). Haplotype analysis
      indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067,
      rs4961 and rs4963 was significantly associated with the BP response to CPT. These
      data suggest that genetic variants of the ADD1 and GNB3 genes may have important
      roles in BP response to the CPT. Future studies aimed at replicating these novel
      findings are warranted.

PMID- 22476229
TI  - Upregulation of endothelium-derived hyperpolarizing factor compensates for the
      loss of nitric oxide in mesenteric arteries of Dahl salt-sensitive hypertensive
      rats.
AB  - This study was designed to determine whether a high-salt diet would alter
      endothelial function and, if so, the relative contributions of endothelium
      derived hyperpolarizing factor (EDHF) and nitric oxide (NO) to any changes in
      vasomotor responses. Male Dahl salt-sensitive (DS) rats were given either a high
      salt diet (8% NaCl, DS-H) or a low-salt diet (0.4% NaCl, DS-L) for 6 weeks.
      Membrane potentials and contractile responses were recorded from the isolated
      superior mesenteric arteries. After salt loading, DS-H developed hypertension,
      while DS-L remained normotensive. No difference was found in acetylcholine (ACh)
      induced, endothelium-dependent relaxation between the groups. However, after
      treatment with indomethacin and NO synthase inhibitor, EDHF-like relaxation was
      significantly greater in DS-H than in DS-L. In contrast, NO-mediated relaxation
      was significantly smaller in DS-Hthan in DS-L. Iberiotoxin (IbTx), a specific
      blocker of large-conductance calcium-dependent potassium (BKCa) channels,
      attenuated EDHF-like relaxation in DS-H but not in DS-L. IbTx marginally
      inhibited EDHF-mediated hyperpolarization only in DS-H. Endothelium-independent
      relaxation in response to sodium nitroprusside or levcromakalim was similar in
      both groups. In conclusion, EDHF-like relaxation is upregulated through the
      activation of BKCa channels in the mesenteric arteries of DS-H. As the overall
      relaxation in response to ACh did not differ between the groups, the upregulation
      of EDHF appears to compensate for the loss of NO in the mesenteric arteries of DS
      H.

PMID- 22476230
TI  - Is home blood pressure variability itself an interventional target beyond
      lowering mean home blood pressure during anti-hypertensive treatment?
AB  - It is unknown whether home blood pressure (BP) variability reduction is
      associated with target organ damage (TOD) protection independently of home mean
      BP reduction. We enrolled 310 hypertensive patients whose systolic BP (SBP) at
      home was over 135 mm Hg. The subjects measured their BP in the morning and
      evening for 7 days. In addition, we measured urinary albumin excretion (UAE) as a
      marker of TOD before and after 6 months of candesartan treatment
      (+thiazidediuretics). At baseline, UAE was associated with average home SBP
      (r=0.24, P<0.001), the s.d. of home SBP (r=0.15, P=0.011), and the maximum home
      SBP (r=0.27, P<0.001). During the intervention, significant reductions were found
      in average home SBP (146+/-13 vs. 132+/-12 mm Hg, P<0.001), s.d. of home SBP
      (12.9+/-4.8 vs. 11.8+/-4.4 mm Hg, P<0.001), and maximum home SBP (172.5+/-18.0
      vs. 155.9+/-17.5 mm Hg, P<0.001). UAE levels were significantly reduced after 6
      months of therapy compared with baseline (18.9 vs. 12.1 mg g(-1) Cre, P<0.001).
      In multiple regression analysis, the treatment-induced reduction in UAE was
      significantly associated with that of average home BP (P=0.003) but was not
      associated with that of s.d. of home SBP or that of maximum home SBP. Home BP
      variability is not itself an interventional target beyond lowering mean home BP
      during anti-hypertensive treatment.

PMID- 22476231
TI  - Hunting for genes for hypertension: the Millennium Genome Project for
      Hypertension.
AB  - The Millennium Genome Project for Hypertension was started in 2000 to identify
      genetic variants conferring susceptibility to hypertension, with the aim of
      furthering the understanding of the pathogenesis of this condition and realizing
      genome-based personalized medical care. Two different approaches were launched,
      genome-wide association analysis using single-nucleotide polymorphisms (SNPs) and
      microsatellite markers, and systematic candidate gene analysis, under the
      hypothesis that common variants have an important role in the etiology of common
      diseases. These multilateral approaches identified ATP2B1 as a gene responsible
      for hypertension in not only Japanese but also Caucasians. The high blood
      pressure susceptibility conferred by certain alleles of ATP2B1 has been widely
      replicated in various populations. Ex vivo mRNA expression analysis in umbilical
      artery smooth muscle cells indicated that reduced expression of this gene
      associated with the risk allele may be an underlying mechanism relating the
      ATP2B1 variant to hypertension. However, the effect size of a SNP was too small
      to clarify the entire picture of the genetic basis of hypertension. Further,
      dense genome analysis with accurate phenotype data may be required.

PMID- 22476232
TI  - Plasma adiponectin levels predict cardiovascular events in the observational
      Arita Cohort Study in Japan: the importance of the plasma adiponectin levels.
AB  - As the plasma level of adiponectin is related to metabolic syndrome and
      cardiovascular events, a low plasma adiponectin level may either cause or trigger
      cardiovascular disorders. The purpose of this study was to determine whether a
      low adiponectin level contributes to cardiovascular events, and to investigate
      the factors influencing adiponectin in the Japanese Arita-cho cohort study.We
      followed about 2000 subjects in Arita-cho, Saga, Japan as a cohort study, and we
      enrolled 637 subjects (205 men; 65.1+/-8.3 years old) who participated in annual
      health checks from 2005 to 2008 and underwent measurement of the plasma
      adiponectin level and an oral glucose tolerance test. We monitored the incidence
      of cardiovascular or cerebrovascular events in these subjects until the end of
      2010, discontinuing follow-up at 3 years after the start of enrollment. Subjects
      with low plasma adiponectin levels (<10.5 ng ml(-1)) had a higher incidence of
      newly diagnosed cardiovascular diseases such as acute heart failure or acute
      myocardial infarction than those with high plasma adiponectin levels (>=10.5 ng
      ml(-1)) over an average of 2.95 years of follow-up. Multivariate analysis showed
      that the adiponectin level was predicted by the following parameters in all
      subjects: age (beta=0.16), male gender (beta=-0.267), homeostasis model
      assessment of insulin resistance (beta=-0.140) and the plasma levels of high
      density lipoprotein cholesterol (beta=0.104), uric acid (beta=-0.13),
      triglycerides (beta=-0.169) and brain natriuretic peptide (beta=0.151). The
      difference in plasma glucose before and 120 min after the intake of a 75-g
      glucose load did not influence the plasma adiponectin level. The plasma
      adiponectin level is useful for predicting cardiovascular events, and is a
      measure of the risk of lifestyle-related diseases.

PMID- 22476233
TI  - Molecular crowding and protein enzymatic dynamics.
AB  - The effects of molecular crowding on the enzymatic conformational dynamics and
      transport properties of adenylate kinase are investigated. This tridomain protein
      undergoes large scale hinge motions in the course of its enzymatic cycle and
      serves as prototype for the study of crowding effects on the cyclic
      conformational dynamics of proteins. The study is carried out at a mesoscopic
      level where both the protein and the solvent in which it is dissolved are treated
      in a coarse grained fashion. The amino acid residues in the protein are
      represented by a network of beads and the solvent dynamics is described by
      multiparticle collision dynamics that includes effects due to hydrodynamic
      interactions. The system is crowded by a stationary random array of hard
      spherical objects. Protein enzymatic dynamics is investigated as a function of
      the obstacle volume fraction and size. In addition, for comparison, results are
      presented for a modification of the dynamics that suppresses hydrodynamic
      interactions. Consistent with expectations, simulations of the dynamics show that
      the protein prefers a closed conformation for high volume fractions. This effect
      becomes more pronounced as the obstacle radius decreases for a given volume
      fraction since the average void size in the obstacle array is smaller for smaller
      radii. At high volume fractions for small obstacle radii, the average enzymatic
      cycle time and characteristic times of internal conformational motions of the
      protein deviate substantially from their values in solution or in systems with
      small density of obstacles. The transport properties of the protein are strongly
      affected by molecular crowding. Diffusive motion adopts a subdiffusive character
      and the effective diffusion coefficients can change by more than an order of
      magnitude. The orientational relaxation time of the protein is also significantly
      altered by crowding. 

PMID- 22476234
TI  - Local anesthetic volume for peripheral nerve blocks: how low can (or should) we
      go?

PMID- 22476235
TI  - Lumbar dural sac dimensions determined by ultrasound helps predict sensory block
      extent during combined spinal-epidural analgesia for labor.
AB  - BACKGROUND AND OBJECTIVES: The lumbosacral cerebrospinal fluid volume is a major
      determinant of the intrathecal spread of local anesthetics. Ultrasound imaging of
      the lumbar spine allows measurement of dural sac dimensions, which may
      potentially be used as a surrogate of cerebrospinal fluid volume. The purpose of
      this study was to investigate the correlation between lumbar dural sac diameter,
      dural sac length (DSL), and dural sac volume (DSV), measured by ultrasound, and
      the intrathecal spread of isobaric bupivacaine during combined spinal-epidural
      (CSE) analgesia for labor. METHODS: We examined 41 women with singleton
      pregnancies requesting neuraxial analgesia for labor. Using a 5-2-MHz curved
      array ultrasound probe in the paramedian sagittal plane, we measured the dural
      sac width at each lumbar interspace and the DSL from L1-2 to L5-S1 interspace and
      calculated the dural sac volume (DSV). Following CSE block with 0.25% isobaric
      bupivacaine 1.75 mg and fentanyl 15 MUg, peak sensory levels (PSLs) were recorded
      using ice, cotton, and pinprick. Statistical correlation coefficients between
      dural sac dimensions and PSLs were assessed by Spearman rank correlation. In
      addition, multiple linear regression models were used to select important
      predictors of PSLs. RESULTS: There was a moderate correlation between DSL and PSL
      to ice (rho = -0.62; P < 0.0005) and to pinprick (rho = -0.52; P = 0.017).
      Similarly, there was a moderate correlation between DSV and PSL to ice (rho = 
      0.56; P = 0.004) and to pinprick (rho = -0.61; P < 0.0008). Neither the DSL nor
      DSV correlated with PSL to cotton. Multiple linear regression analysis revealed
      that DSL, weight, and body mass index contributed to PSLs. CONCLUSIONS: The
      length of the lumbar spine determined by ultrasound, rather than the lumbar spine
      volume, combined with the weight or body mass index of the subject, is of
      particular value in predicting the intrathecal spread of isobaric bupivacaine
      during CSE analgesia for labor.

PMID- 22476236
TI  - Incidence and effects of unintentional intraneural injection during ultrasound
      guided subgluteal sciatic nerve block.
AB  - BACKGROUND: The present study was conducted to determine the incidence of
      unintentional intraneural injection during ultrasound-guided subgluteal sciatic
      nerve block using a low-frequency transducer. We also observed the effects of
      intraneural injection using ropivacaine and mepivacaine. METHODS: Enrolled in the
      study were 325 patients undergoing arthroscopic knee surgery, who each received a
      subgluteal sciatic nerve block under ultrasound guidance using 1.5% mepivacaine
      with 1:400,000 epinephrine or 0.5% ropivacaine. A block needle was inserted in
      plane with the ultrasound transducer (5-2 MHz curved array) and advanced slowly
      under real-time ultrasound guidance until it was positioned immediately adjacent
      to the nerve. Twenty milliliters of either anesthetic was then injected to
      produce a circumferential spread. An ultrasound video was recorded and used to
      examine whether the local anesthetic was injected intraneurally. Sensory and
      motor blockade was evaluated for 30 mins after completion of the block. Duration
      of the block and any neurologic complications were also examined. RESULTS:
      Intraneural injection was detected in 46 patients (16.3%; 95% confidence
      interval, 12.3%-20.3%). Onset of sensory and motor blockade was significantly
      faster in patients with intraneural injection than those without either
      mepivacaine or ropivacaine. Duration of sensory blockade was similar between
      patients with and without intraneural injection. No patient developed
      postoperative neurologic complications. CONCLUSIONS: Unintentional intraneural
      injection occurred at an incidence rate of 16.3% for the ultrasound-guided
      subgluteal approach to the sciatic nerve. Intraneural injection of mepivacaine or
      ropivacaine hastened the onset of blockade but did not affect block duration, and
      it did not result in clinical neural injury in our small sample of patients.

PMID- 22476237
TI  - Pulsed radiofrequency in the treatment of persistent pain after inguinal
      herniotomy: a systematic review.
AB  - In the United States, it is estimated that between 6000 and 18,000 individuals
      each year present with disabling pain after inguinal hernia repair. Although
      surgical treatment with mesh removal is one of few options available, effective
      alternatives to nonsurgical management are needed. The use of pulsed
      radiofrequency (PFR), leading to nondestructive lesions of nerve structures, has
      been proposed as a treatment option. To examine the evidence of treatment
      efficacy, a systematic literature search was made. From the databases PubMed,
      Embase, and CINAHL, 4 case reports were retrieved and 8 patients were included
      for analysis. The PFR treatment was peripheral (n = 4) and central (n = 4). Pain
      relief varied between 63% and 100%, the follow-up period was 3 to 9 months, and
      no adverse effects or complications were reported. In conclusion, the evidence
      base of PRF in persistent pain after inguinal herniotomy is fairly limited.
      Suggestions for improved research strategies are presented.

PMID- 22476238
TI  - Near-infrared tracking system for epidural catheter placement: a feasibility
      study.
AB  - BACKGROUND: Epidural catheters are routinely used in regional and obstetric
      anesthesia. The flexible catheter is advanced without imaging control into the
      epidural space, and coiling or kinking of the catheter may occur, compromising
      the effectiveness of epidural anesthesia. Potentially near-infrared (NER) light
      detection may help, tracking advancement of the catheter in the epidural space.
      METHODS: Nonembalmed human cadavers donated to the University of Washington
      Willed Body program were placed prone. Catheters containing NER-emitting wire
      were introduced into the lumbar and thoracic epidural space. The progress of the
      emitting wire was tracked using the LumenVu NER guidance system, and the final
      location of the catheter was confirmed with fluoroscopy. RESULTS: Total 12
      attempts were made to place the catheter. In 7 cases (4 lumbar and 3 thoracic),
      good progression of the catheter in the epidural space was achieved with
      excellent visibility at low NER power levels. Maximum light intensity was
      registered when the catheter tip was found in the midline dorsal interlaminar
      position, as confirmed by fluoroscopy. The light intensity decreased while the
      catheter tip was traversing under the lamina. Poor progression of the catheter
      with negligible visibility of the tip at the highest NER level occurred in obese
      specimen (n = 2) or when the tip was in extraforaminal (n = 1), paramedian or
      paravertebral positions (n = 2). CONCLUSIONS: Many variables such as obesity,
      paravertebral and extraforaminal catheter locations, and intervening bony
      structures can impede the application of NER technology for epidural catheter
      placements. Further optimization of the technology for clinical use is necessary.

PMID- 22476239
TI  - Distribution patterns, dermatomal anesthesia, and ropivacaine serum
      concentrations after bilateral dual transversus abdominis plane block.
AB  - BACKGROUND AND OBJECTIVES: The ability of transversus abdominis plane (TAP)
      blocks to anesthetize the upper abdomen remains debatable. We aimed to describe
      the local anesthetic distribution following ultrasound-guided TAP blocks with
      repeated magnetic resonance imaging investigations and to relate this to the
      resulting dermatomal anesthesia. METHODS: Eight volunteers were included in a
      randomized, observer-blinded study. Sixty milliliters of ropivacaine 0.375% was
      administered: 1 injection of 30 mL as a lateral classic TAP block, followed by a
      sham upper intercostal TAP block, and on the contralateral side, 2 separate 15-mL
      injections at the upper intercostal and lateral classic TAP plexuses,
      respectively. The primary outcome measure was magnetic resonance imaging-assessed
      area expansion of all injectates over a 6-hr period. Dermatomal anesthesia and
      sequential serum ropivacaine levels were recorded at the same time intervals.
      RESULTS: All injectate areas expanded in a statistically significant manner in
      the anterior abdominal wall. Lateral classic TAP blocks with 30-mL injectates did
      not extend into the upper intercostal TAP plexus. The dual 15-mL injectates on
      the other hemiabdomen remained within the upper intercostal and lateral classic
      TAP compartments and resulted in significantly (P < 0.018) more widespread
      dermatomal anesthesia. Measured serum ropivacaine concentrations were below the
      potential level of toxicity. CONCLUSIONS: Magnetic resonance imaging analysis
      revealed a significant time-dependent expansion of injectates. Magnetic resonance
      imaging and the degree of dermatomal anesthesia confirmed that the upper and
      lateral TAP compartments do not appear to communicate. Separate injections at the
      upper intercostal and lateral classic TAP plexuses are necessary to block the
      entire abdominal wall.

PMID- 22476241
TI  - A low-cost, durable, combined ultrasound and fluoroscopic phantom for cervical
      transforaminal injections.
AB  - BACKGROUND: This technical report describes a durable, low-cost, anatomically
      accurate, and easy-to-prepare combined ultrasound (US) and fluoroscopic phantom
      of the cervical spine. This phantom is meant to augment training in US- and
      fluoroscopic-guided pain medicine procedures. METHODS: The combined US and
      fluoroscopic phantom (CUF-P) is prepared from commercially available liquid
      plastic that is ordinarily used to prepare synthetic fishing lures. The liquid
      plastic is heated and then poured into a metal canister that houses an anatomical
      cervical spine model. Drops of dark purple dye are added to make the phantom
      opaque. After cooling, tubing is attached to the CUF-P to simulate blood vessels.
      RESULTS: The CUF-P accurately simulates human tissue by imitating both the
      tactile texture of skin and the haptic resistance of human tissue as the needle
      is advanced. This phantom contains simulated fluid-filled vertebral arteries that
      exhibit pulsed flow under color Doppler US. Under fluoroscopic examination, the
      CUF-P-simulated vertebral arteries also exhibit uptake of contrast dye if
      mistakenly injected. CONCLUSIONS: The creation of a training phantom allows the
      pain physician to practice needle positioning technique while simultaneously
      visualizing both targeted and avoidable vascular structures under US and
      fluoroscopic guidance. This low-cost CUF-P is easy to prepare and is reusable,
      making it an attractive alternative to current homemade and commercially
      available phantom simulators.

PMID- 22476240
TI  - Addition of pregabalin to multimodal analgesic therapy following ankle surgery: a
      randomized double-blind, placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Pregabalin is often used as a perioperative analgesic
      adjunct; some studies show benefit, but others do not. Adverse effects, such as
      confusion and sedation, have been attributed to perioperative use of pregabalin.
      We tested the hypothesis that pregabalin, when used as part of a multimodal
      analgesic regimen, reduces the duration of moderate to severe pain in the first
      24 hrs following foot or ankle surgery. Secondary outcomes included measures of
      opioid and pregabalin adverse effects. METHODS: Sixty patients scheduled for
      hospital admission after foot or ankle surgery entered this randomized, double
      blind, placebo-controlled trial. Patients received a neuraxial anesthetic, a
      popliteal fossa sciatic nerve block using 30 mL 0.375% bupivacaine with clonidine
      100 ug and epinephrine, a saphenous nerve block, postoperative hydromorphone
      intravenous patient-controlled analgesia, and oral analgesics
      (oxycodone/acetaminophen). Patients were randomized to receive pregabalin (100 mg
      preoperatively, then 50 mg every 12 hrs) or a placebo for 3 days. The primary
      outcome was the number of hours that patients reported moderate to severe pain.
      RESULTS: Both groups reported a similar number of hours of moderate to severe
      pain during the first 24 hrs: 4.1 (SD, 4.1) hrs (pregabalin) versus 4.5 (SD, 3.5)
      hrs (placebo). Pain scores, opioid use, and adverse effects were also similar in
      both groups. CONCLUSIONS: No clinical benefit was obtained from perioperative
      administration of pregabalin (100 mg preoperative, then 50 mg every 12 hrs) as
      part of a multimodal postoperative analgesic regimen following foot and ankle
      surgery.

PMID- 22476242
TI  - Amplitude modulation of sexy phrases is salient for song attractiveness in female
      canaries (Serinus canaria).
AB  - Song discrimination and recognition in songbird species have usually been studied
      by measuring responses to song playbacks. In female canaries, Serinus canaria,
      copulation solicitation displays (CSDs) are used as an index of female
      preferences, which are related to song recognition. Despite the fact that many
      studies underline the role of song syntax in this species, we observed that short
      segments of songs (a few seconds long) are enough for females to discriminate
      between conspecific and heterospecific songs, whereas such a short duration is
      not sufficient to identify the syntax rules. This suggests that other cues are
      salient for song recognition. In this experiment, we investigated the influence
      of amplitude modulation (AM) on the responses (CSDs) of female canaries to song
      playbacks. We used two groups of females: (1) raised in acoustic isolation and
      (2) raised in normal conditions. When adult, we tested their preferences for sexy
      phrases with different AMs. We broadcast three types of stimuli: (1) songs with
      natural canary AM, (2) songs with AM removed, or (3) song with wren Troglodytes
      troglodytes AM. Results indicate that female canaries prefer and have
      predispositions for a song type with the natural canary AM. Thus, this acoustic
      parameter is a salient cue for song attractiveness.

PMID- 22476243
TI  - Psychosocial, educational, and somatic factors in chronic nonspecific low back
      pain.
AB  - Analysis of the effect of psychosocial factors and co-morbidities on the health
      status of patients with chronic nonspecific low back pain and patients with
      surgical intervention because of disk herniation was performed. One hundred and
      two nonselected consecutive inpatients with chronic nonspecific low back pain
      were included in the study. Their average age was 56.7 (SD = 10.9) years. The
      control group consisted of 199 subjects matched according to age and sex, chosen
      from the database of the national representative health survey Hungarostudy 2006,
      which involved 4,527 subjects. We measured quality of life including mental
      health with the SF-36 questionnaire validated for use in Hungary, the short 9
      item version of the Beck Depression Inventory, the WHO-Five Well-Being Index, and
      the Hospital Anxiety-Depression Scale. We characterized the socio-demographic
      status with variables on age, sex, marital status, and education. Data on
      symptoms and signs of low back pain, other musculoskeletal diseases, and their
      treatments including spinal surgery were recorded. Co-morbidity and body mass
      index were considered as independent indicators of health. Depression as measured
      by Beck Depression Inventory and severity of depression did not vary
      significantly according to marital status, education, hypertension, diabetes, and
      gastrointestinal disease. Only half of the patients (52 %) were in the normal
      range of the scale; 22 % suffered from mild, 16 % from moderate, and 12 % from
      severe depression. Average values for anxiety and depression as measured by
      Hospital Anxiety-Depression Scale and Beck Depression Inventory were both
      significantly higher in the patient than in the control group (Hospital Anxiety
      Scale: p = 0.0001; Beck Depression Inventory: p = 0.0001). According to the WHO
      Well-Being Index-5 scale, the difference between patients and the control group
      was significant (p = 0.0001). Furthermore, correlation was found between the
      incidence of depression and surgery. Depression was demonstrated in 47.4 % of
      those patients who had no surgery, in 50 % of patients who had one round of
      surgery, and in 62.5 % of those who had undergone surgery more than once; the
      contingence coefficient was 0.211. According to different measurements, the
      psychological state of patients with chronic nonspecific low back pain was
      significantly altered as compared to the matched Hungarian population. Higher
      anxiety and depression markers occurred in 48 % of the patients. There was no
      correlation between the depression of patients with low back pain and variables
      such as marital status, education, and co-morbidities. Our study is the first to
      demonstrate that depression runs parallel with the number of surgical procedures.
      Therefore, if there is a relative indication for surgery, depression and severity
      of depression should be assessed and considered when deciding on the
      intervention.

PMID- 22476244
TI  - Effects of glucosamine sulfate and exercise therapy on serum leptin levels in
      patients with knee osteoarthritis: preliminary results of randomized controlled
      clinical trial.
AB  - Osteoarthritis (OA) is a slow, chronic disease characterized by the focal
      deterioration and abrasion of articular cartilage. Leptin may play an important
      role in the pathophysiology of OA. Exercise and glucosamine sulfate therapy is
      one of the most commonly used in patients with knee OA. The goals of the present
      study are performed to investigate whether 12-week strength training program and
      glucosamine sulfate have an effect on serum leptin levels in knee OA and the
      relationship between leptin, clinical parameters, and radiographic severity of
      knee OA. Thirty-seven women with the diagnosis of knee OA were enrolled in the
      study. Patients were randomized into two groups. Group I (n = 19) received an
      exercise program, while group II (n = 18) received glucosamine sulfate (1,500
      mg/day) in addition to the exercise therapy. Both groups were treated for 12
      weeks. Leptin level was assessed at baseline and after 12 weeks. The
      concentration of leptin was measured by ELISA. The patients were evaluated
      regarding pain, disability, functional performance, and muscle strength. Both
      groups showed significant improvements in leptin levels, pain, disability, muscle
      strength, and functional performance with no statistically significant difference
      between the groups after the therapy. At basal time, plasma leptin levels were
      significantly correlated with body mass index and duration of disease, but no
      significant correlation was found with patient age, pain, disability, functional
      performance, muscle strength, and radiographic severity of knee OA. The results
      of this preliminary study revealed that exercise alone was adequate to prevent
      structural changes relieving the symptoms of OA. We also found that exercise
      alone could affect serum plasma levels of the leptin, important mediators of
      cartilage metabolism. Decreases in serum leptin may be one mechanism by which
      cartilage metabolism affects physical function and symptoms in OA patients.

PMID- 22476245
TI  - Discriminative and diagnostic value of anti-cyclic citrullinated peptide
      antibodies in Iranian patients with rheumatoid arthritis.
AB  - Most studies on the diagnostic utility of the anti-cyclic citrullinated peptide
      antibody (anti-CCP) test in rheumatoid arthritis (RA) have been performed in
      developed countries, with only a few done in the developing world. We undertook a
      cross-sectional study to determine the diagnostic utility of the rheumatoid
      factor (RF) and anti-CCP tests in urbanized Iranians with early RA. One hundred
      and ninety-three serum samples were obtained from consecutive patients who were
      diagnosed with RA. Serum samples of 254 ones without RA, consisting of other
      inflammatory polyarthritis disorders, were also collected as controls. RF was
      measured for IgM by latex agglutination test, and titers higher than 1/80 were
      considered positive. Anti-CCP was also assayed using an ELISA with 6.25 RU/ml as
      the threshold for a positive result. The anti-CCP had sensitivity, specificity,
      positive predictive value, and negative predictive value for a diagnosis of RA of
      47.2, 92.9, 83.5, and 69.8 %, respectively. Those for RF were 57.0, 83.9, 72.8,
      and 72.0 %, respectively. For anti-CCP antibodies in combination with RF, they
      were 38.9, 96.5, 89.3, and 67.5 %, respectively. Anti-CCP has higher specificity
      and predictive values compared with the RF parameter in diagnosing RA in Iranian
      patients, but their discriminative values were similar. Anti-CCP and RF in
      combination further increases the diagnostic value for RA.

PMID- 22476246
TI  - Carpal tunnel syndrome and metabolic syndrome co-occurrence.
AB  - We aimed to evaluate the relation between the severity of carpal tunnel syndrome
      and metabolic syndrome. One hundred and fifty patients who had a clinical and
      electrophysiologically confirmed diagnosis of carpal tunnel syndrome (CTS), were
      included in this study. The patients were divided into two groups (with or
      without metabolic syndrome) according to the criteria of National Cholesterol
      Education Program. Eighty one (73.5 %) of the patients with CTS had metabolic
      syndrome. The patients with metabolic syndrome the severity of CTS was found 22.2
      % had mild CTS, 56.8 % had moderate CTS, and 21 % had severe CTS. The patients
      without metabolic syndrome the severity of CTS was found 44.9 % had mild CTS,
      40.6 % had moderate CTS, and 14.5 % had severe CTS. The severity of CTS between
      both groups was found to be statistically significant (p = 0.0009). While a
      correlation was found between the severity of CTS and high level of LDL with the
      presence of metabolic syndrome (correlation coefficient 0.209). In conclusion
      metabolic syndrome that appears to be a risk factor for CTS. At the same time,
      the presence of metabolic syndrome increases the severity of the disease.

PMID- 22476247
TI  - Enantiospecific kinking of DNA by a partially intercalating metal complex.
AB  - Opposite enantiomers of [Ru(phenanthroline)(3)](2+) affect the persistence length
      of DNA differently, a long speculated effect of helix kinking. Our molecular
      dynamics simulations confirm a substantial change of duplex secondary structure
      produced by wedge-intercalation of one but not the other enantiomer. This effect
      is exploited by several classes of DNA operative proteins.

PMID- 22476248
TI  - Infection, mutation, and cancer evolution.
AB  - An understanding of oncogenesis can be fostered by an integration of mechanistic
      studies with evolutionary considerations, which help explain why these mechanisms
      occur. This integration emphasizes infections and mutations as joint essential
      causes for many cancers. It suggests that infections may play a broader causal
      role in oncogenesis than has been generally appreciated. An evolutionary
      perspective also suggests that oncogenic viruses will tend to be transmitted by
      routes that provide infrequent opportunities for transmission, such as
      transmission by sexual and salivary contact. Such routes increase the intensity
      of natural selection for persistence within hosts, and molecular mechanisms for
      persistence often compromise critical barriers to oncogenesis, particularly cell
      cycle arrest, apoptosis, and a cap on the total number of divisions that a cell
      can undergo.

PMID- 22476249
TI  - Ambulatory blood pressure in prehypertensive children and adolescents.
AB  - BACKGROUND: Prehypertension is defined as blood pressure (BP) >= 90 th
      percentile, or >= 120/80 mmHg, but <95th percentile for age, sex, and height.
      Since the definition is made by conventional BP measurements and office BP can be
      quite variable, we studied whether prehypertension could be differentiated by
      ambulatory BP monitoring from normotension or hypertension (HTN) in children and
      adolescents. METHODS: One hundred and fifty-eight children (84 boys and 74 girls,
      aged 6-17 years, median 12) were studied. According to the office BP values, they
      were divided into normotension (80), prehypertension (20), and HTN (58). RESULTS:
      Systolic BP index and systolic daytime ambulatory BP (ABP) were significantly
      higher in prehypertensive patients than in normotensives and lower than
      hypertensives. When daytime ABP was used to diagnose HTN, four normotensive
      (5.0%), four prehypertensive (20.0%), and 27 hypertensive (46.6%) patients had
      HTN. Thus, in patients with prehypertension, the prevalence of masked HTN is
      significantly higher than in those with normotension. On the other hand, the
      prevalence of daytime ambulatory HTN is significantly lower, i.e., white-coat
      effect is more frequent, compared with hypertensive patients. CONCLUSION:
      Prehypertension lies between normotension and HTN in ABP values as well and is a
      good candidate for identifying masked HTN. Our data emphasize the importance of
      identifying prehypertension in children and adolescents.

PMID- 22476250
TI  - "Strawberry wees forever?": questions.

PMID- 22476252
TI  - The contribution of systematic reviews to the practice of pediatric nephrology.
AB  - The key to accurate decision-making is to use the best available evidence.
      Systematic reviews aim to identify and combine evidence using systematic methods
      to minimize bias to provide reliable data for patient care. While systematic
      reviews can address different clinical questions, the methodology is most
      developed for systematic reviews of randomized controlled trials. Such systematic
      reviews include all available trial evidence, enhance the precision of the
      estimates of treatment effects, and identify where evidence is lacking or where
      sufficient evidence is already available. However the term "systematic review"
      does not guarantee that a review covers all the available data, that the validity
      of included studies has been appropriately assessed, or that data have been
      combined appropriately in meta-analyses. Biases in systematic review include
      those related to identifying data (publication bias, language bias, selective
      reporting of outcomes) and those due to the design and conduct of trials
      (selection bias, performance bias, detection bias, attrition bias). Thus, readers
      should read a systematic review carefully before accepting its results and
      conclusions. This review examines the information that can be provided by
      systematic reviews of randomized controlled trials together with the biases that
      can potentially jeopardize the results and conclusions.

PMID- 22476253
TI  - Ru-catalyzed beta-selective and enantioselective addition of amines to styrenes
      initiated by direct arene-exchange.
AB  - A catalytic beta-selective addition of amines to styrenes proceeded in the
      presence of cationic Ru complexes combined with diphosphine ligands. In the
      reaction of alpha-methylstyrene, an enantioselective addition was achieved by
      using xylylBINAP.

PMID- 22476254
TI  - Effectiveness of three configurations of membrane bioreactors on the removal of
      priority and emergent organic compounds from wastewater: comparison with
      conventional wastewater treatments.
AB  - In this work the effectiveness of membrane bioreactors as advanced treatment on
      the removal of emergent and priority organic compounds in wastewater treatment
      plants has been evaluated during a one-year monitoring study. The studied
      wastewater treatment plant operates with flat sheet and hollow fibre membranes in
      two parallel lines. Moreover, a reverse osmosis module connected in series after
      the hollow fibre membrane was evaluated for one month. Comparison of membrane
      bioreactor and conventional activated sludge treatment was also investigated, as
      well as the influence of the physicochemical properties of the compounds on the
      removal rates achieved. Sixteen pharmaceutical compounds belonging to seven
      therapeutic groups and eight priority organic pollutants, including linear
      alkylbenzene sulfonates, nonylphenol and its ethoxylates and phthalate, were
      monitored. The highest mean concentrations corresponded to priority organic
      pollutants (309 MUg L(-1) of linear alkylbenzene sulfonate C(12)) followed by
      pharmaceutical compounds (24.5 MUg L(-1) of ibuprofen). No significant difference
      of effectiveness was found among flat sheet and hollow fibre membranes. However,
      an improvement was obtained with the addition of a reverse osmosis module for
      most of the compounds. Biodegradation has been shown as the main route involved
      in the removal of organic compounds during both technologies.

PMID- 22476255
TI  - Bioaccumulation of phenol, guaiacol and some chlorophenols by selected freshwater
      species of leeches.
AB  - In the recent study, the bioaccumulation ability of phenolic substances was
      determined with field-collected specimens of three leech species, i.e.,
      Erpobdella octoculata (Linnaeus), Theromyzon tessulatum (O. F. Muller) and
      Glossiphonia complanata (Linneaus). It was found that the examined leeches
      bioaccumulated phenol (0.03-27.10 mg/kg), 4-methylphenol (0.09-1.83 mg/kg),
      chlorophenols (0.03-14.90 mg/kg), guaiacol (0.22-2,941 mg/kg),
      tetrachloroguaiacol (0.06-1.98 mg/kg), 3-chlorosyringol (0.04-15.28 mg/kg) and
      chlorocatechols (0.33-23.24 mg/kg) present in the water (0.03-25.23 MUg/L) and in
      the bottom sediments (0.75-760.5 MUg/kg) of three ecosystems that were
      characterized by different contamination levels. Analysis of both the external
      mucous coat of the leeches and the tissue of the dermato-muscular sac showed that
      substantial quantities of the phenolic compounds may be accumulated in both the
      mucous (0.03-2,941 mg/kg) and the tissue (0.03-1,189.8 mg/kg).

PMID- 22476256
TI  - Metal contamination in market based vegetables in an industrial region, India.
AB  - Concentrations of metals were determined in market vegetables in Ghaziabad
      industrial region. The average concentrations of metals (mg/kg dry wt.) in
      vegetables ranged from 0.57 to 9.77, 0.72 to 22.17, 2.76 to 46.63, 2.53 to 5.53,
      28.87 to 65.94, 6.77 to 74.1, 8.43 to 161.1, 23.46 to 36.55 and 4.74 to 24.18 for
      Cu, Cr, Pb, Cd, Zn, Mn, Fe, Ni and Co, respectively. Pb, Cd and Ni were above the
      recommended limit in all the examined vegetables.

PMID- 22476257
TI  - Persistence of bifenthrin in sandy loam soil as affected by microbial community.
AB  - Soil was fortified with bifenthrin at the level of 10 MUg g(-1) soil. Soil
      samples were drawn at regular intervals of 0, 10, 20, 30 and 40 days. For
      extraction of bifenthrin, soil was extracted with acetone. Clean up was done by
      liquid-liquid partitioning with dichloromethane after diluting with brine
      solution. Quantification of bifenthrin residues was done by GC using mega bore
      column and ECD detector. Recovery of bifenthrin in soil ranged between 92.6 % and
      93.8 % at 0.5 and 1.0 MUg g(-1). The instrumental limit of detection of
      bifenthrin was 0.005 MUg mL(-1) and LOQ for soil by this method was found to be
      0.05 MUg g(-1). The calibration curve was found to be linear within range the
      range of 0.01 and 0.10 MUg mL(-1) concentration. The DT(50) (disappearance time
      for 50 % loss) of bifenthrin at the level of 10 MUg g(-1) in sterile and non
      sterile soil were found to be 330 and 147 days, respectively. A vast difference
      in the half life of sterile and non sterile soil indicated the presence of
      potential microbes for bifenthrin degradation.

PMID- 22476258
TI  - Identification of trace organic pollutants in drinking water and the associated
      human health risks in Jiangsu Province, China.
AB  - Organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs),
      dibutyl phthalate (DNBP) and di-2-ethylhexyl phthalate (DEHP) were all detectable
      in surface water in Jiangsu Province, China. Concentrations of OCPs ranged from
      5.13 to 8.15 ng/L. PAHs were found ranging from 14.7 to 24.5 ng/L. Concentrations
      of DNBP and DEHP ranged from 16 to 5,857.5 ng/L and 556 to 15,670.7 ng/L,
      respectively. Greater than 70 % of chemicals were removed in water treatment
      processes. The carcinogenic risks posed by trace organic pollutants through tap
      water ingestion were lower than 10(-6), and the noncarcinogenic risks were less
      than 10(-5).

PMID- 22476259
TI  - Estimation of etofenprox residues in tomato fruits by QuEChERS methodology and
      HPLC-DAD.
AB  - Etofenprox residues were estimated by employing standardized QuEChERS technique
      in tomato following one application of Trebon((r)) 20 % EC. The average
      recoveries of etofenprox on tomato for fortification levels 0.01, 0.1 and 0.5
      mg/kg were observed to be 87.5 %, 89.7 % and 92.2 %, respectively, with relative
      standard division of 3.50, 4.11 and 3.20. The LOQ for tomato was found to be 0.01
      mg/kg. The average initial deposit of etofenprox on tomato was observed to be
      0.783 mg/kg, at single application rate. This etofenprox residue dissipated below
      its LOQ of 0.01 after 15 days at a single dosage. Half-life of etofenprox was
      observed to be 2.15 days, at the recommended dosage. These data could provide
      guidance for the proper and safe use of this pesticide on tomato in Egypt.

PMID- 22476260
TI  - Ultrastructural analysis of flagellar development in plurilocular sporangia of
      Ectocarpus siliculosus (Phaeophyceae).
AB  - Flagellar development in the plurilocular zoidangia of sporophytes of the brown
      alga Ectocarpus siliculosus was analyzed in detail using transmission electron
      microscopy and electron tomography. A series of cell divisions in the
      plurilocular zoidangia produced the spore-mother cells. In these cells, the
      centrioles differentiated into flagellar basal bodies with basal plates at their
      distal ends and attached to the plasma membrane. The plasma membrane formed a
      depression (flagellar pocket) into where the flagella elongated and in which
      variously sized vesicles and cytoplasmic fragments accumulated. The anterior and
      posterior flagella started elongating simultaneously, and the vesicles and
      cytoplasmic fragments in the flagellar pocket fused to the flagellar membranes.
      The two flagella (anterior and posterior) could be clearly distinguished from
      each other at the initial stage of their development by differences in length,
      diameter and the appendage flagellar rootlets. Flagella continued to elongate in
      the flagellar pocket and maintained their mutually parallel arrangement as the
      flagellar pocket gradually changed position. In mature zoids, the basal part of
      the posterior flagellum (paraflagellar body) characteristically became swollen
      and faced the eyespot region. Electron dense materials accumulated between the
      axoneme and the flagellar membrane, and crystallized materials could also be
      observed in the swollen region. Before liberation of the zoospores from the
      plurilocular zoidangia, mastigoneme attachment was restricted to the distal
      region of the anterior flagellum. Structures just below the flagellar membrane
      that connected to the mastigonemes were clearly visible by electron tomography.

PMID- 22476261
TI  - Expression and location of phospho-Artemis (Serine516) in hair follicles during
      induced growth of mouse hair.
AB  - Artemis has been implicated in having a role in NHEJ, and it is also a
      multifunctional protein. Previous studies have found Omenn syndrome-like
      phenotype due to Artemis mutations and associated with alopecia. As Artemis
      phosphorylation in its c-terminus including Serine516 is prerequisite for the
      Artemis endonuclease reaction, we postulate that Artemis (Serine516) may be
      expressed in hair follicle and relate to hair cycling. In this study, hair growth
      in C57BL/6 mice was induced by plucking the telogen hair on the back. Expression
      of Artemis (Serine516) in hair follicles during the hair growth cycle was
      evaluated by immunofluorescence using cryosections and a specific polyclonal anti
      Artemis (Serine516) immunoglobulin G (IgG) antibody. It was detected in germ
      cells, cap, and club hair adjoining the epidermis in telogen. In anagen II,
      intense staining for Artemis (Serine516) was found in the whole interfollicular
      epidermis, and in strand keratinocytes. In anagen IV, intense staining for
      Artemis (Serine516) was detected in basal cells and upper of outer root sheath
      (ORS) and inner root sheath (IRS). But only upper ORS and lower medulla were
      stained positive in anagen VI. Upper ORS and lower cortex were positively stained
      with Artemis (Serine516) in catagen. Based on the phenomenon that the expression
      of Artemis (Serine516) in mid-anagen and mature anagen was stronger than that in
      telogen and catagen, we suggest it may take roles in induced growth of mouse
      hair.

PMID- 22476262
TI  - Detection of an internal translation activity in the 5' region of Bombyx mori
      infectious flacherie virus.
AB  - The 5' untranslated region plays an important role in positive-sense single
      stranded RNA virus translation initiation, as it contains an internal ribosome
      entry site (IRES) that mediates cap-independent translation and is applied to
      simultaneously express several proteins. Infectious flacherie virus (IFV) is a
      positive-sense single-stranded RNA virus; however, the IRES function is still not
      proved. To investigate whether the sequences of IFV contain IRES activity, a
      series of bicistronic reporter (DsRed and enhanced green fluorescent protein)
      recombinant baculoviruses were constructed to infect the insect cells and
      silkworm using the Bombyx mori baculovirus expression system. Results showed that
      the upstream 311, 323, 383, 551, and 599 nt have IRES activity except for the 155
      nt region in BmN cells. More importantly, the tetraloop structure containing
      region between 551 and 599 nt appeared to be responsible for the enhanced IRES
      activity in different insect cell lines and silkworm. These results indicated
      that the IRES activity is not species specific and tissue specific. Therefore,
      our findings may provide the basis for the simultaneous expression of two or
      various different genes under the same promoter in baculovirus expression system.

PMID- 22476263
TI  - Key players and team play: anaerobic microbial communities in hydrocarbon
      contaminated aquifers.
AB  - Biodegradation of anthropogenic pollutants in shallow aquifers is an important
      microbial ecosystem service which is mainly brought about by indigenous anaerobic
      microorganisms. For the management of contaminated sites, risk assessment and
      control of natural attenuation, the assessment of in situ biodegradation and the
      underlying microbial processes is essential. The development of novel molecular
      methods, "omics" approaches, and high-throughput techniques has revealed new
      insight into complex microbial communities and their functions in anoxic
      environmental systems. This review summarizes recent advances in the application
      of molecular methods to study anaerobic microbial communities in contaminated
      terrestrial subsurface ecosystems. We focus on current approaches to analyze
      composition, dynamics, and functional diversity of subsurface communities, to
      link identity to activity and metabolic function, and to identify the
      ecophysiological role of not yet cultured microbes and syntrophic consortia. We
      discuss recent molecular surveys of contaminated sites from an ecological
      viewpoint regarding degrader ecotypes, abiotic factors shaping anaerobic
      communities, and biotic interactions underpinning the importance of microbial
      cooperation for microbial ecosystem services such as contaminant degradation.

PMID- 22476264
TI  - Upconversion nanoparticles modified with aminosilanes as carriers of DNA vaccine
      for foot-and-mouth disease.
AB  - The potential of the upconversion nanoparticles
      NaYF(4):Yb/Er@silica(UCPs)/plasmid DNA (pcDNA3.1/VP1-GFP) complex in inducing
      immune responses was evaluated using the UCPs as carriers of the foot-and-mouth
      disease virus (FMDV AsiaI/Jiangsu2005) DNA vaccine. The UCPs protection against
      DNaseI degradation was measured using an in vitro inhibition assay. The
      expression of the plasmid in vivo was determined via confocal microscopy. Its
      biocompatibility was evaluated through cytotoxicity assay. Based on the results,
      the aminosilane-modified UCPs can electrostatically bind, condense, and protect
      plasmid DNA. Cell viability assays demonstrated that the cytotoxicity of the
      UCPs/plasmid DNA complex is lower than that of the cationic lipid/plasmid DNA
      complex, and that the transfection efficiency of UCPs is the same as that of the
      cationic lipid. Furthermore, the UCP/plasmid DNA complex was intramuscularly
      administered to guinea pigs. Humoral and cellular immune responses were detected
      using indirect enzyme-linked immunosorbent assay (ELISA), micro-neutralization
      assay, and T-lymphocyte proliferation assay. Anti-FMDV specific antibodies,
      neutralizing antibodies, and T-lymphocyte proliferation responses were induced
      after vaccination. In the challenge test, all the guinea pigs vaccinated with the
      UCPs/plasmid DNA complex were fully protected from the FMDV challenge. The
      current study encourages the use of UCPs as an effective nanosystem for gene
      delivery to cells for in vitro and in vivo vaccination, and other therapeutic
      applications.

PMID- 22476265
TI  - Water-seeking behavior in worm-infected crickets and reversibility of parasitic
      manipulation.
AB  - One of the most fascinating examples of parasite-induced host manipulation is
      that of hairworms, first, because they induce a spectacular "suicide" water
      seeking behavior in their terrestrial insect hosts and, second, because the
      emergence of the parasite is not lethal per se for the host that can live several
      months following parasite release. The mechanisms hairworms use to increase the
      encounter rate between their host and water remain, however, poorly understood.
      Considering the selective landscape in which nematomorph manipulation has evolved
      as well as previously obtained proteomics data, we predicted that crickets
      harboring mature hairworms would display a modified behavioral response to light.
      Since following parasite emergence in water, the cricket host and parasitic worm
      do not interact physiologically anymore, we also predicted that the host would
      recover from the modified behaviors. We examined the effect of hairworm infection
      on different behavioral responses of the host when stimulated by light to record
      responses from uninfected, infected, and ex-infected crickets. We showed that
      hairworm infection fundamentally modifies cricket behavior by inducing directed
      responses to light, a condition from which they mostly recover once the parasite
      is released. This study supports the idea that host manipulation by parasites is
      subtle, complex, and multidimensional.

PMID- 22476266
TI  - Forearm bone mineral density varies as a function of adiposity in inuit women 40
      90 years of age during the vitamin D-synthesizing period.
AB  - Aging Inuit women are at increased risk for low vitamin D status due to
      habitation at higher latitudes, darker skin, and ongoing nutrition transition.
      Lower serum 25-hydroxyvitamin D (25[OH]D) concentration and higher risk of
      fracture have been separately reported in Inuit women, with particular relevance
      to postmenopausal women. We evaluated vitamin D status, forearm bone mineral
      density (fBMD), and nutrition in Inuit women >=40 years. Women (n = 568) were
      randomly selected to participate in the 2007-2008 International Polar Year Inuit
      Health Survey from 36 Arctic communities. fBMD was measured using peripheral dual
      energy X-ray absorptiometry. Dietary intakes were derived from 24 h recall and
      food-frequency questionnaires. Fasting serum 25(OH)D, parathyroid hormone, and
      osteocalcin (OC) were measured using a LIAISON((r)) automated analyzer. The
      weighted prevalence of women having 25(OH)D concentration below 37.5, 50, and 75
      nmol/L was 7.2 %, 17.6 %, and 48.6 %, respectively, with older women having
      better status. The dietary density of most nutrients increased with age, as did
      traditional food intake. fBMD was low in 3 (1.4 %) premenopausal (Z score < -2)
      and 107 (29.6 %) postmenopausal (T score < -1.5) women. Regression revealed that
      either weight, body mass index, or percent body fat significantly predicted fBMD
      in premenopausal women, in addition to age and OC in postmenopausal women. Women
      >=50 years have higher vitamin D status and more nutrient-dense diets than women
      40-49 years. While measures of adiposity predicted fBMD in all women, additional
      predictors after menopause included age and bone turnover.

PMID- 22476267
TI  - The effect of care pathways for hip fractures: a systematic review.
AB  - We performed a systematic review for primary studies on care pathways (CPs) for
      hip fracture (HF). The online databases MEDLINE-PubMed, Ovid-EMBASE, CINAHL-EBSCO
      host, and The Cochrane Library (Cochrane Central Register of Clinical Trials,
      Health Technology Assessment Database, NHS Economic Evaluation Database) were
      searched. Two researchers reviewed the literature independently. Primary studies
      that met predefined inclusion criteria were assessed for their methodological
      quality. A total of 15 publications were included: 15 primary studies
      corresponding with 12 main investigations. Primary studies were evaluated for
      clinical outcomes, process outcomes, and economic outcomes. The studies assessed
      a wide range of outcome measures. While a number of divergent clinical outcomes
      were reported, most studies showed positive results of process management and
      health-services utilization. In terms of mortality, the results provided evidence
      for a positive impact of CPs on in-hospital mortality. Most studies also showed a
      significantly reduced risk of complications, including medical complications,
      wound infections, and pressure sores. Moreover, time-span process measures showed
      that an improvement in the organization of care was achieved through the use of
      CPs. Conflicting results were observed with regard to functional recovery and
      mobility between patients treated with CPs compared to usual care. Although our
      review suggests that CPs can have positive effects in patients with HF, the
      available evidence is insufficient for formal recommendations. There is a need
      for more research on CPs with selected process and outcome indicators, for in
      hospital and postdischarge management of HF, with an emphasis on well-designed
      randomized trials.

PMID- 22476268
TI  - Statewide validation of hospital-reported central line-associated bloodstream
      infections: Oregon, 2009.
AB  - BACKGROUND: Mandatory reporting of healthcare-associated infections is common,
      but underreporting by hospitals limits meaningful interpretation. OBJECTIVE: To
      validate mandatory intensive care unit (ICU) central line-associated bloodstream
      infection (CLABSI) reporting by Oregon hospitals. DESIGN: Blinded comparison of
      ICU CLABSI determination by hospitals and health department-based external
      reviewers with group adjudication. SETTING: Forty-four Oregon hospitals required
      by state law to report ICU CLABSIs. PARTICIPANTS: Seventy-six patients with ICU
      CLABSIs and a systematic sample of 741 other patients with ICU-related bacteremia
      episodes. METHODS: External reviewers examined medical records and determined
      CLABSI status. All cases with CLABSI determinations discordant from hospital
      reporting were adjudicated through formal discussion with hospital staff, a
      process novel to validation of CLABSI reporting. RESULTS: Hospital
      representatives and external reviewers agreed on CLABSI status in 782 (96%) of
      817 bacteremia episodes (k = 0.77 [95% confidence interval (CI), 0.70-0.84]).
      Among the 27 episodes identified as CLABSIs by external reviewers but not
      reported by hospitals, the final status was CLABSI in 16 (59%). The measured
      sensitivities of hospital ICU CLABSI reporting were 72% (95% CI, 62%-81%) with
      adjudicated CLABSI determination as the reference standard and 60% (95% CI, 51%
      69%) with external review alone as the reference standard (P = .07). Validation
      increased the statewide ICU CLABSI rate from 1.21 (95% CI, 0.95-1.51) to 1.54
      (95% CI, 1.25-1.88) CLABSIs/1,000 central line-days; ICU CLABSI rates increased
      by more than 1.00 CLABSI/1,000 central line-days in 6 (14%) hospitals.
      CONCLUSIONS: Validating hospital CLABSI reporting improves accuracy of hospital
      based CLABSI surveillance. Discussing discordant findings improves the quality of
      validation.

PMID- 22476269
TI  - Building data quality and confidence in data reported to the National Healthcare
      Safety Network.

PMID- 22476270
TI  - Sustained improvements in peripheral venous catheter care in non-intensive care
      units: a quasi-experimental controlled study of education and feedback.
AB  - BACKGROUND AND OBJECTIVES: Peripheral venous catheters (PVCs) can be associated
      with serious infectious complications. We evaluated the effect of education and
      feedback on process measures to improve PVC care and infectious complications.
      DESIGN: Quasi-experimental controlled crossover study with sampling before and
      after education. SETTING: An 804-bed tertiary care teaching hospital.
      PARTICIPANTS: Nurses and patients in 10 non-intensive care units. METHODS: We
      implemented a process to improve PVC care in 10 non-intensive care units. The 4
      periods (each 3 months in duration) included a preintervention period and a
      staggered educational intervention among nurses. During intervention period 1, 5
      units participated in the intervention (group A), and 5 units served as a control
      group (group B). Group B underwent the intervention during intervention period 2,
      and both groups A and B received feedback on performance during intervention
      period 3. Process measures were evaluated twice monthly, and feedback was given
      to nurses directly and to the unit manager on a monthly basis. RESULTS: During
      the preintervention period, there were no significant differences between groups
      A and B. Of 4,904 intravascular catheters evaluated, 4,434 (90.4%) were
      peripheral. By the end of the study, there were significant improvements in
      processes, compared with the preintervention period, including accurate
      documentation of dressing (from 442 cases [38%] to 718 cases [59%]; P < .0001),
      catheter dressing being intact (from 968 cases [88.5%] to 1,024 cases [95.2%]; P
      < .0001), and correct demonstration of scrubbing the hub before infusion (from
      161 demonstrations [54%] to 316 demonstrations [95%]; P < .0001). There was a
      significant reduction in PVC-associated bloodstream infection, from 2.2 cases per
      10,000 patient-days during the preintervention period (5 cases) to 0.44 cases per
      10,000 patient days during the 3 intervention periods (3 cases; P = .016).
      CONCLUSIONS: Education and real-time feedback to nurses increases and sustains
      compliance with processes to reduce the risk of infection from PVCs.

PMID- 22476271
TI  - Healthcare-associated bloodstream infections secondary to a urinary focus: the
      Quebec provincial surveillance results.
AB  - OBJECTIVE: Urinary tract infections (UTIs) are an important source of secondary
      healthcare-associated bloodstream infections (BSIs), where a potential for
      prevention exists. This study describes the epidemiology of BSIs secondary to a
      urinary source (U-BSIs) in the province of Quebec and predictors of mortality.
      DESIGN: Dynamic cohort of 9,377,830 patient-days followed through a provincial
      voluntary surveillance program targeting all episodes of healthcare-associated
      BSIs occurring in acute care hospitals. SETTING: Sixty-one hospitals in Quebec,
      followed between April 1, 2007, and March 31, 2010. PARTICIPANTS: Patients
      admitted to participating hospitals for 48 hours or longer. METHODS: Descriptive
      statistics were used to summarize characteristics of U-BSIs and microorganisms
      involved. Wilcoxon and chi(2) tests were used to compare U-BSI episodes with
      other BSIs. Negative binomial regression was used to identify hospital
      characteristics associated with higher rates. We explored determinants of
      mortality using logistic regression. RESULTS: Of the 7,217 reported BSIs, 1,510
      were U-BSIs (21%), with an annual rate of 1.4 U-BSIs per 10,000 patient-days. A
      urinary device was used in 71% of U-BSI episodes. Identified institutional risk
      factors were average length of stay, teaching status, and hospital size.
      Increasing hospital size was influential only in nonteaching hospitals. Age,
      nonhematogenous neoplasia, Staphylococcus aureus, and Foley catheters were
      associated with mortality at 30 days. CONCLUSION: U-BSI characteristics suggest
      that urinary catheters may remain in patients for ease of care or because
      practitioners forget to remove them. Ongoing surveillance will enable hospitals
      to monitor trends in U-BSIs and impacts of process surveillance that will be
      implemented shortly.

PMID- 22476272
TI  - Improved risk adjustment in public reporting: coronary artery bypass graft
      surgical site infections.
AB  - OBJECTIVE: The objective was to develop a new National Healthcare Safety Network
      (NHSN) risk model for sternal, deep incisional, and organ/space (complex)
      surgical site infections (SSIs) following coronary artery bypass graft (CABG)
      procedures, detected on admission and readmission, consistent with public
      reporting requirements. PATIENTS AND SETTING: A total of 133,503 CABG procedures
      with 4,008 associated complex SSIs reported by 293 NHSN hospitals in the United
      States. METHODS: CABG procedures performed from January 1, 2006, through December
      31, 2008, were analyzed. Potential SSI risk factors were identified by univariate
      analysis. Multivariate analysis with forward stepwise logistic regression
      modeling was used to develop the new model. The c-index was used to compare the
      predictive power of the new and NHSN risk index models. RESULTS: Multivariate
      analysis independent risk factors included ASA score, procedure duration, female
      gender, age, and medical school affiliation. The new risk model has significantly
      improved predictive performance over the NHSN risk index (c-index, 0.62 and 0.56,
      respectively). CONCLUSIONS: Traditionally, the NHSN surveillance system has used
      a risk index to provide procedure-specific risk-stratified SSI rates to
      hospitals. A new CABG sternal, complex SSI risk model developed by multivariate
      analysis has improved predictive performance over the traditional NHSN risk index
      and is being considered for endorsement as a measure for public reporting.

PMID- 22476274
TI  - Cost-effectiveness analysis of active surveillance screening for methicillin
      resistant Staphylococcus aureus in an academic hospital setting.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of 3 alternative active screening
      strategies for methicillin-resistant Staphylococcus aureus (MRSA): universal
      surveillance screening for all hospital admissions, targeted surveillance
      screening for intensive care unit admissions, and no surveillance screening.
      DESIGN: Cost-effectiveness analysis using decision modeling. METHODS: Cost
      effectiveness was evaluated from the perspective of an 800-bed academic hospital
      with 40,000 annual admissions over the time horizon of a hospitalization. All
      input probabilities, costs, and outcome data were obtained through a
      comprehensive literature review. Effectiveness outcome was MRSA healthcare
      associated infections (HAIs). One-way and probabilistic sensitivity analyses were
      conducted. RESULTS: In the base case, targeted surveillance screening was a
      dominant strategy (ie, was associated with lower costs and resulted in better
      outcomes) for preventing MRSA HAI. Universal surveillance screening was
      associated with an incremental cost-effectiveness ratio of $14,955 per MRSA HAI.
      In one-way sensitivity analysis, targeted surveillance screening was a dominant
      strategy across most parameter ranges. Probabilistic sensitivity analysis also
      demonstrated that targeted surveillance screening was the most cost-effective
      strategy when willingness to pay to prevent a case of MRSA HAI was less than
      $71,300. CONCLUSION: Targeted active surveillance screening for MRSA is the most
      cost-effective screening strategy in an academic hospital setting. Additional
      studies that are based on actual hospital data are needed to validate this model.
      However, the model supports current recommendations to use active surveillance to
      detect MRSA.

PMID- 22476273
TI  - A multicenter study of Clostridium difficile infection-related colectomy, 2000
      2006.
AB  - OBJECTIVE: To assess Clostridium difficile infection (CDI)-related colectomy
      rates by CDI surveillance definitions and over time at multiple healthcare
      facilities. SETTING: Five university-affiliated acute care hospitals in the
      United States. DESIGN AND METHODS: Cases of CDI and patients who underwent
      colectomy from July 2000 through June 2006 were identified from 5 US tertiary
      care centers. Monthly CDI-related colectomy rates were calculated as the number
      of CDI-related colectomies per 1,000 CDI cases, and cases were categorized
      according to recommended surveillance definitions. Logistic regression was
      performed to evaluate risk factors for CDI-related colectomy. RESULTS: In total,
      8,569 cases of CDI were identified, and 75 patients underwent CDI-related
      colectomy. The overall colectomy rate was 8.7 per 1,000 CDI cases. The CDI
      related colectomy rate ranged from 0 to 23 per 1,000 CDI episodes across
      hospitals. The colectomy rate for healthcare-facility-onset CDI was 4.3 per 1,000
      CDI cases, and that for community-onset CDI was 16.5 per 1,000 CDI cases (P <
      .05). There were significantly more CDI-related colectomies at hospitals B and C
      (P < .05). CONCLUSIONS: The overall CDI-related colectomy rate was low, and there
      was no significant change in the CDI-related colectomy rate over time. Onset of
      disease outside the study hospital was an independent risk factor for colectomy.

PMID- 22476275
TI  - Effectiveness of selected surgical masks in arresting vegetative cells and
      endospores when worn by simulated contagious patients.
AB  - OBJECTIVE: The objective of this study was to quantify the effectiveness of
      selected surgical masks in arresting vegetative cells and endospores in an
      experimental model that simulated contagious patients. SETTING: Laboratory.
      METHODS: Five commercially available surgical masks were tested for their ability
      to arrest infectious agents. Surgical masks were placed over the nose and mouth
      of mannequin head forms (Simulaids adult model Brad CPR torso). The mannequins
      were retrofitted with a nebulizer attached to an automated breathing simulator
      calibrated to a tidal volume of 500 mL/breath and a breathing rate of 20
      breaths/min, for a minute respiratory volume of 10 L/min. Aerosols of endospores
      or vegetative cells were generated with a modified microbiological research
      establishment-type 6-jet collision nebulizer, while air samples were taken with
      all-glass impinger (AGI-30) samplers downstream of the point source. All
      experiments were conducted in a horizontal bioaerosol chamber. RESULTS: Mean
      arrestance of bioaerosols by the surgical masks ranged from 48% to 68% when the
      masks were challenged with endospores and from 66% to 76% when they were
      challenged with vegetative cells. When the arrestance of endospores was
      evaluated, statistical differences were observed between some pairs, though not
      all, of the models evaluated. There were no statistically significant differences
      in arrestance observed between models of surgical masks challenged with
      vegetative cells. CONCLUSIONS: The arrestance of airborne vegetative cells and
      endospores by surgical masks worn by simulated contagious patients supports
      surgical mask use as one of the recommended cough etiquette interventions to
      limit the transmission of airborne infectious agents.

PMID- 22476276
TI  - Gaseous chlorine dioxide as an alternative for bedbug control.
AB  - OBJECTIVE: This study evaluated the efficacy of gaseous chlorine dioxide (ClO(2))
      for extermination of bedbugs (Cimex lectularius and Cimex hemipterus).
      BACKGROUND: Bedbugs have received attention because of recent outbreaks. Bedbug
      eradication is difficult and often requires a time-consuming multifaceted
      approach. SETTING: Laboratory and hospital room. METHODS: Bedbugs were exposed to
      concentrations of ClO(2) of 362, 724, and 1,086 parts per million (ppm) in an
      exposure chamber. Bedbug mortality was then evaluated. The ability of ClO(2) to
      penetrate various spaces in a hospital room was evaluated using Bacillus
      atropheus as a surrogate organism. RESULTS: Concentrations of 1,086 and 724 ppm
      of ClO(2) yielded 100% bedbug mortality assessed immediately after exposure. Live
      young were not observed for any eggs exposed to ClO(2) gas. ClO(2) at a
      concentration of 362 ppm for 1,029 parts per million hours (ppm-hours) achieved
      100% mortality 6 hours after exposure. A ClO(2) concentration of 362 ppm for 519
      ppm-hours had 100% mortality 18 hours after exposure. Up to a 6-log reduction in
      B. atropheus spores was achieved using similar concentrations of ClO(2) in a
      hospital room, indicating that the concentrations needed to kill bedbugs can be
      achieved throughout a hospital room. CONCLUSIONS: ClO(2) is effective at killing
      bedbugs in the laboratory, and similar concentrations of ClO(2) gas can be
      achieved in a hospital room. ClO(2) can be removed from the room without
      residuals.

PMID- 22476277
TI  - Use of a structured panel process to define quality metrics for antimicrobial
      stewardship programs.
AB  - INTRODUCTION: Antimicrobial stewardship programs are being implemented in health
      care to reduce inappropriate antimicrobial use, adverse events, Clostridium
      difficile infection, and antimicrobial resistance. There is no standardized
      approach to evaluate the impact of these programs. OBJECTIVE: To use a structured
      panel process to define quality improvement metrics for evaluating antimicrobial
      stewardship programs in hospital settings that also have the potential to be used
      as part of public reporting efforts. DESIGN: A multiphase modified Delphi
      technique. SETTING: Paper-based survey supplemented with a 1-day consensus
      meeting. PARTICIPANTS: A 10-member expert panel from Canada and the United States
      was assembled to evaluate indicators for relevance, effectiveness, and the
      potential to aid quality improvement efforts. RESULTS: There were a total of 5
      final metrics selected by the panel: (1) days of therapy per 1000 patient-days;
      (2) number of patients with specific organisms that are drug resistant; (3)
      mortality related to antimicrobial-resistant organisms; (4) conservable days of
      therapy among patients with community-acquired pneumonia (CAP), skin and soft
      tissue infections (SSTI), or sepsis and bloodstream infections (BSI); and (5)
      unplanned hospital readmission within 30 days after discharge from the hospital
      in which the most responsible diagnosis was one of CAP, SSTI, sepsis or BSI. The
      first and second indicators were also identified as useful for accountability
      purposes, such as public reporting. CONCLUSION: We have successfully identified 2
      measures for public reporting purposes and 5 measures that can be used internally
      in healthcare settings as quality indicators. These indicators can be implemented
      across diverse healthcare systems to enable ongoing evaluation of antimicrobial
      stewardship programs and complement efforts for improved patient safety.

PMID- 22476278
TI  - Comparison of the microbiological efficacy of hydrogen peroxide vapor and
      ultraviolet light processes for room decontamination.
AB  - OBJECTIVE: To compare the microbiological efficacy of hydrogen peroxide vapor
      (HPV) and ultraviolet radiation (UVC) for room decontamination. DESIGN:
      Prospective observational study. SETTING: 500-bed teaching hospital. METHODS: HPV
      and UVC processes were performed in 15 patient rooms. Five high-touch sites were
      sampled before and after the processes and aerobic colony counts (ACCs) were
      determined. Carrier disks with ~10(6) Clostridium difficile (CD) spores and
      biological indicators (BIs) with 10(4) and 10(6) Geobacillus stearothermophilus
      spores were placed in 5 sites before decontamination. After decontamination, CD
      log reductions were determined and BIs were recorded as growth or no growth.
      RESULTS: 93% of ACC samples that had growth before HPV did not have growth after
      HPV, whereas 52% of sites that had growth before UVC did not have growth after
      UVC (P < .0001). The mean CD log reduction was >6 for HPV and ~2 for UVC. After
      HPV 100% of the 10(4) BIs did not grow, and 22% did not grow after UVC, with a
      range of 7%-53% for the 5 sites. For the 10(6) BIs, 99% did not grow after HPV
      and 0% did not grow after UVC. Sites out of direct line of sight were
      significantly more likely to show growth after UVC than after HPV. Mean cycle
      time was 153 (range, 140-177) min for HPV and 73 (range, 39-100) min for UVC (P <
      .0001). CONCLUSION: Both HPV and UVC reduce bacterial contamination, including
      spores, in patient rooms, but HPV is significantly more effective. UVC is
      significantly less effective for sites that are out of direct line of sight.

PMID- 22476279
TI  - Impact of isolation on hospital consumer assessment of healthcare providers and
      systems scores: is isolation isolating?
AB  - The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS)
      survey was used to measure the effect of isolation on patient satisfaction.
      Isolated patients reported lower scores for questions regarding physician
      communication and staff responsiveness. Overall scores for these domains were
      lower in isolated than in nonisolated patients.

PMID- 22476280
TI  - Bacterial contamination of an automated pharmacy robot used for intravenous
      medication preparation.
AB  - Multiple cultures were positive for Bacillus cereus during routine quality
      assurance testing of a pharmacy robot that prepares intravenous medications. An
      investigation confirmed bacterial contamination of the robot as well as drug
      product made by the robot. The process and outcomes of the investigation are
      described in this report.

PMID- 22476281
TI  - Surveillance system of hemodialysis-associated infections in a pediatric unit.
AB  - The bloodstream infection surveillance system proposed by the Centers for Disease
      Control and Prevention (CDC) was prospectively conducted in a pediatric
      hemodialysis unit. Thirty patients were included; 73% had a catheter for vascular
      access at enrollment. Vascular access infection rate was 21.1 per 100 patient
      months, well above those observed in adult patient surveys. Staphylococcus aureus
      was most frequently isolated (23%).

PMID- 22476282
TI  - Blood culture collection through peripheral intravenous catheters increases the
      risk of specimen contamination among adult emergency department patients.
AB  - Five hundred five blood cultures collected through a peripheral intravenous
      catheter (PIV) in an emergency department were matched to cultures obtained by
      dedicated venipuncture from the same patient within 10 minutes. The relative risk
      of contamination for cultures collected through PIVs compared with dedicated
      venipuncture was 1.83 (95% confidence interval, 1.08-3.11).

PMID- 22476283
TI  - Effects of chlorhexidine oral decontamination on respiratory colonization during
      mechanical ventilation in intensive care unit patients.
AB  - We conducted a retrospective cohort study to assess respiratory colonization
      before and after the use of chlorhexidine oral decontamination among a cohort of
      intensive care unit patients who received mechanical ventilation. We observed a
      decrease in the prevalence of Enterobacteriaceae and an increase in the incidence
      of fungal colonization. Chlorhexidine oral decontamination might have a
      differential effect on respiratory colonization.

PMID- 22476284
TI  - Can we expect patients to question health care workers' hand hygiene compliance?

PMID- 22476285
TI  - Impact of the change in surveillance definitions on the rates of urinary tract
      infection in intensive care units: 1988 versus 2009 definitions.

PMID- 22476286
TI  - Environmental decontamination with ultraviolet radiation to prevent recurrent
      Clostridium difficile infection in 2 roommates in a long-term care Facility.

PMID- 22476287
TI  - Polymyxin B consumption and incidence of gram-negative bacteria intrinsically
      resistant to polymyxins.

PMID- 22476290
TI  - Developmental, cytological and transcriptional analysis of autotetraploid
      Arabidopsis.
AB  - An autopolyploid that contains more than two sets of the same chromosomes causes
      apparent alterations in morphology, development, physiology and gene expression
      compared to diploid. However, the mechanisms for these changes remain largely
      unknown. In the present study, cytological observations of mature embryos and
      growing cotyledons demonstrated that enlarged organ size of an autotetraploid
      Arabidopsis was caused by cell size and not by cell number. Quantitative real
      time PCR (qRT-PCR) analysis of 34 core cell cycle genes revealed a subtle but
      stable increase in the expression of ICK1, ICK2 and ICK5 in autotetraploid
      seedlings. Autotetraploid Arabidopsis plants were found to be more sensitive to
      glucose treatment than diploid with decreased number of rosette leaves and
      suppressed root elongation. Cytological observations demonstrated that both cell
      proliferation and cell expansion of autotetraploid were dramatically suppressed
      under glucose treatment. Expression levels of ICK1, ICK5 together with Cyclin D
      and Cyclin B was increased under glucose treatment in both diploid and
      autotetraploid plants. These results suggest that ICK1 and ICK5 may be involved
      in developmental delay and that the suppressed growth under glucose treatment
      probably resulted from disturbed mitotic and endoreduplication cycle in
      autotetraploid Arabidopsis.

PMID- 22476291
TI  - Narciclasine inhibits the responses of Arabidopsis roots to auxin.
AB  - The plant hormone auxin plays a central role in the regulation of plant growth
      and development, as well as in responses to environmental stimuli. Narciclasine
      (NCS, an Amaryllidaceae alkaloid) isolated from Narcissus tazetta bulbs has a
      broad range of inhibitory effects on plants. In this study, the role of NCS in
      responses to auxin in Arabidopsis thaliana roots was investigated. We
      demonstrated the inhibitory effects of NCS on auxin-inducible lateral root
      formation, root hair formation, primary root growth, and the expression of
      primary auxin-inducible genes in Arabidopsis roots using DR5::GUS reporter gene,
      native auxin promoters (IAA12::GUS, IAA13::GUS), and quantitative reverse
      transcription PCR analysis. Results also showed that NCS did not affect the
      expression of cytokinin-inducible ARR5::GUS reporter gene. NCS relieved the auxin
      enhanced degradation of the Aux/IAA repressor modulated by the SCFTIR1 ubiquitin
      proteasome pathway. In addition, NCS did not alter the auxin-stimulated
      interaction between IAA7/AXR2 (Aux/IAA proteins) and the F-box protein TIR1
      activity of the proteasome. Taken together, these results suggest that NCS acts
      on the auxin signaling pathway upstream of TIR1, which modulates Aux/IAA protein
      degradation, and thereby affects the auxin-mediated responses in Arabidopsis
      roots.

PMID- 22476292
TI  - Overexpression of a Medicago truncatula stress-associated protein gene (MtSAP1)
      leads to nitric oxide accumulation and confers osmotic and salt stress tolerance
      in transgenic tobacco.
AB  - The impact of Medicago truncatula stress-associated protein gene (MtSAP1)
      overexpression has been investigated in Nicotiana tabacum transgenic seedlings.
      Under optimal conditions, transgenic lines overexpressing MtSAP1 revealed better
      plant development and higher chlorophyll content as compared to wild type
      seedlings. Interestingly, transgenic lines showed a stronger accumulation of
      nitric oxide (NO), a signaling molecule involved in growth and development
      processes. This NO production seemed to be partially nitrate reductase dependent.
      Due to the fact that NO has been also reported to play a role in tolerance
      acquisition of plants to abiotic stresses, the responses of MtSAP1 overexpressors
      to osmotic and salt stress have been studied. Compared to the wild type,
      transgenic lines were less affected in their growth and development. Moreover, NO
      content in MtSAP1 overexpressors was always higher than that detected in wild
      seedlings under stress conditions. It seems that this better tolerance induced by
      MtSAP1 overexpression could be associated with this higher NO production that
      would enable seedlings to reach a high protection level to prepare them to cope
      with abiotic stresses.

PMID- 22476294
TI  - The need to prioritize smoking cessation.

PMID- 22476293
TI  - Rice PLASTOCHRON genes regulate leaf maturation downstream of the gibberellin
      signal transduction pathway.
AB  - Rice PLASTOCHRON 1 (PLA1) and PLA2 genes regulate leaf maturation and
      plastochron, and their loss-of-function mutants exhibit small organs and rapid
      leaf emergence. They encode a cytochrome P450 protein CYP78A11 and an RNA-binding
      protein, respectively. Their homologs in Arabidopsis and maize are also
      associated with plant development/organ size. Despite the importance of PLA genes
      in plant development, their molecular functions remain unknown. Here, we
      investigated how PLA1 and PLA2 genes are related to phytohormones. We found that
      gibberellin (GA) is the major phytohormone that promotes PLA1 and PLA2
      expression. GA induced PLA1 and PLA2 expression, and conversely the GA-inhibitor
      uniconazole suppressed PLA1 and PLA2 expression. In pla1-4 and pla2-1 seedlings,
      expression levels of GA biosynthesis genes and the signal transduction gene were
      similar to those in wild-type seedlings. GA treatment slightly down-regulated the
      GA biosynthesis gene GA20ox2 and up-regulated the GA-catabolizing gene GA2ox4,
      whereas the GA biosynthesis inhibitor uniconazole up-regulated GA20ox2 and down
      regulated GA2ox4 both in wild-type and pla mutants, suggesting that the GA
      feedback mechanism is not impaired in pla1 and pla2. To reveal how GA signal
      transduction affects the expression of PLA1 and PLA2, PLA expression in GA
      signaling mutants was examined. In GA-insensitive mutant, gid1 and less-sensitive
      mutant, Slr1-d1, PLA1 and PLA2 expression was down-regulated. On the other hand,
      the expression levels of PLA1 and PLA2 were highly enhanced in a GA-constitutive
      active mutant, slr1-1, causing ectopic overexpression. These results indicate
      that both PLA1 and PLA2 act downstream of the GA signal transduction pathway to
      regulate leaf development.

PMID- 22476296
TI  - Datapoints: Reported mental health specialty care in the 2010 HealthStyles
      Survey.

PMID- 22476297
TI  - Law & psychiatry: Responsibility for torts: should the courts continue to ignore
      mental illness?
AB  - Although courts routinely consider whether a criminal defendant's mental illness
      makes punishment unfair, the rules are very different for civil liability. When
      people with mental illness harm others, courts refuse to consider their mental
      states in determining civil liability. The justifications offered for this rule
      range from the difficulty of assessing the impact of mental illness on behavior
      to the desire to place the burden of loss on the person who caused the injury.
      Undeniably, though, mental disabilities are treated differently from physical
      impairments, and the law's resistance to change seems largely based on
      misunderstanding and prejudice against mental illness.

PMID- 22476299
TI  - Personal accounts: Forgiveness: moving from anger and shame to self-love.

PMID- 22476300
TI  - Mental health spending by private insurance: implications for the mental health
      parity and addiction equity act.
AB  - OBJECTIVE: The study developed information on behavioral health spending and
      utilization that can be used to anticipate, evaluate, and interpret changes in
      health care spending following implementation of the Mental Health Parity and
      Addiction Equity Act (MHPAEA). METHODS: Data were from the Thomson Reuters'
      MarketScan database of insurance claims between 2001 and 2009 from large group
      health plans sponsored by self-insured employers. Annual rates in growth of total
      health spending and behavioral health spending and the contribution of behavioral
      health spending to growth in spending for all diseases were determined. Separate
      analyses examined behavioral health and total health spending by 135 employers in
      2008 and 2009, and simulations were conducted to determine how increases in use
      of mental health services after implementation of parity would affect overall
      health care expenditures. RESULTS: Across the nine years examined, behavioral
      health expenditures contributed .3%, on average, to the total rate of growth in
      all health expenditures, a contribution that fell to .1%, on average, when
      prescription drugs were excluded. About 2% of employers experienced an increased
      contribution by behavioral health spending of more than 1%. More than 90% of
      enrollees used well below the maximum 30 inpatient days or outpatient visits
      typical of health insurance plans before parity. Simulations indicated that even
      large increases in utilization would increase total health care expenditures by
      less than 1%. CONCLUSIONS: The MHPAEA is unlikely to have a large effect on the
      growth rate of employers' health care expenditures. The data provide baseline
      information to further evaluate the implementation effect of the MHPAEA.

PMID- 22476301
TI  - Assessment of therapy practices in community treatment for children and
      adolescents.
AB  - OBJECTIVE: The Monthly Treatment and Progress Summary (MTPS) was developed to
      assess treatment techniques applied in clinical practice. This study examined the
      factor structure of the reported therapeutic practice elements on the MTPS and
      explored patterns in technique use based on client and therapist characteristics
      in a community mental health setting. METHODS: MTPS data from 278 lead therapists
      in Hawai'i's local system of care were extracted from the online state mental
      health information management system. Therapists' endorsements (yes-no) of each
      practice element were examined across 278 completed youth treatment episodes, and
      an exploratory factor analysis with varimax rotation was conducted on the
      categorical data set. RESULTS: Three factors emerged from the analyses: behavior
      management (behavioral interventions), coping and self-control (self-change
      practices), and family interventions (family supports). Treatment teams with
      licensed therapists reported higher use of coping and self-control practice
      elements, whereas teams with unlicensed therapists and paraprofessionals reported
      greater use of behavior management practice elements. Lead therapists reported
      that teams treating younger clients and those with attentional disorders were
      more likely to use behavior management practice elements, and teams treating
      youths with more severe impairment at intake utilized more behavior management
      and family intervention practice elements. CONCLUSIONS: Overall, the MTPS shows
      promise as a therapist report of practices. The finding that practice elements
      organized into theoretical patterns and were applied in expected ways suggests a
      thoughtful approach to usual care techniques. With the increased focus on health
      care reform and managed care, the MTPS can inform system monitoring, feedback,
      and improvement.

PMID- 22476302
TI  - Service utilization by hospitalized suicide attempters with schizophrenia or
      depression in Montreal.
AB  - OBJECTIVE: The purpose of this study was to analyze patterns of mental health
      related service utilization before and after hospitalization for attempting
      suicide. METHODS: This retrospective cohort study included all persons 15 years
      or older with a clinical diagnosis of schizophrenia (N=195) or depression (N=330)
      hospitalized in Montreal, Quebec, from April 2003 to December 2004 for attempting
      suicide. Data on the publicly managed health and social services system were
      retrieved from the linked administrative databases of Montreal's Health and
      Social Services Agency (April 2002 to March 2005). Twelve-month preattempt
      service utilization profile, health care contacts three months pre- and
      postattempt, and predictors of postattempt service utilization were analyzed for
      two diagnostic groups (schizophrenia and depression). RESULTS: Specialized
      outpatient care and hospital emergency departments were the services most used by
      both groups before and after attempting suicide. Use of hospital emergency
      services as a primary care service did not adequately ensure aftercare, whereas
      prior contact with services and concurrent substance use disorder predicted
      greater service utilization postattempt among men but not women. CONCLUSIONS: The
      publicly managed health and social services system in Montreal seems to respond
      rather well to severe suicide attempts, including those by men with a concurrent
      substance use disorder known to be at high suicide risk. However, better
      coordination among hospital emergency departments, primary care, specialized
      mental health services, and addiction services is needed in order to enhance
      continuity of care.

PMID- 22476303
TI  - Diversion of patients with mental illness from court-ordered care to immigration
      detention.
AB  - Over 350,000 immigrants are detained by U.S. Immigration and Customs Enforcement
      (ICE) each year. An unknown fraction of these detainees have serious mental
      illnesses and are taken into ICE custody even though a criminal court has ordered
      them to enter inpatient mental health care. The authors report findings from 16
      such cases in which they have provided advocacy over the past four years. In some
      cases, they were able to secure release of detainees into inpatient care in
      community (nonforensic) settings, which involved substantial logistical
      challenges. Given the well-documented concerns about securing adequate care for
      ICE detainees with mental illness, a logical policy change would be for ICE to
      allow these patients to enter court-ordered inpatient care. This move would
      improve care for patients and would also unburden ICE from the untenable
      proposition of caring for patients that the criminal justice system has deemed
      unfit for incarceration.

PMID- 22476304
TI  - Association of perceived barriers with prospective use of VA mental health care
      among Iraq and Afghanistan veterans.
AB  - OBJECTIVE: The relationship between perceived barriers and prospective use of
      mental health care among veterans was examined. METHODS: The sample included Iraq
      and Afghanistan veterans (N=305) who endorsed symptoms of depression or
      posttraumatic stress disorder (PTSD) or alcohol misuse at intake to a
      postdeployment clinic between May 2005 and August 2009. Data on receipt of
      adequate treatment (nine or more mental health visits in the year after intake)
      were obtained from a VA database. RESULTS: Adequate treatment was more likely for
      women (odds ratio [OR]=4.82, 95% confidence interval (CI)=1.37-16.99, p=.014) and
      for those with more severe symptoms of PTSD (OR=1.03, CI=1.01-1.05, p=.003) and
      depression (OR=1.06, CI=1.01-1.11, p=.01). Perceived barriers were not associated
      with adequate treatment. CONCLUSIONS: Male veterans with mental health problems
      should be targeted with outreach to reduce unmet need. Research is needed to
      identify perceived barriers to treatment among veterans.

PMID- 22476305
TI  - Outcomes of 98,609 U.S. Department of Veterans Affairs patients enrolled in
      telemental health services, 2006-2010.
AB  - OBJECTIVE: The study assessed clinical outcomes of 98,609 mental health patients
      before and after enrollment in telemental health services of the U.S. Department
      of Veterans Affairs between 2006 and 2010. METHODS: The study compared number of
      inpatient psychiatric admissions and days of psychiatric hospitalization among
      patients who participated in remote clinical videoconferencing during an average
      period of six months before and after their enrollment in the telemental health
      services. RESULTS: Between 2006 and 2010, psychiatric admissions of telemental
      health patients decreased by an average of 24.2% (annual range 16.3%-38.7%), and
      the patients' days of hospitalization decreased by an average of 26.6% (annual
      range 16.5%-43.5%). The number of admissions and the days of hospitalization
      decreased for both men and women and in 83.3% of the age groups. CONCLUSIONS:
      This four-year study, the first large-scale assessment of telemental health
      services, found that after initiation of such services, patients' hospitalization
      utilization decreased by an average of approximately 25%.

PMID- 22476306
TI  - Does a study focused on trauma encourage patients with psychotic symptoms to seek
      treatment?
AB  - OBJECTIVE: This study explored, in a randomized trial of psychotherapies for
      posttraumatic stress disorder (PTSD), why a surprisingly high percentage of study
      applicants presented with psychotic symptoms and what clinical implications this
      finding might prompt. METHODS: Raters reviewed the records of applicants who
      completed an initial psychiatric interview and compared those who had psychotic
      symptoms with all other study-eligible participants and with those who ultimately
      were enrolled in the study. RESULTS: Of 223 consecutively evaluated individuals
      who applied for study entry, 38 (17%) were found ineligible because of psychotic
      symptoms. These individuals were more likely to be male and to have suffered
      child abuse, and they had taken a greater number of lifetime medications than
      study-eligible applicants. Most individuals with psychotic symptoms met DSM-IV
      criteria for PTSD. CONCLUSIONS: A trauma-informed framework might be a helpful
      part of a comprehensive treatment plan for some individuals with psychotic
      symptoms, possibly leading to greater treatment engagement and more positive
      outcomes.

PMID- 22476307
TI  - Rates of trauma-informed counseling at substance abuse treatment facilities:
      reports from over 10,000 programs.
AB  - OBJECTIVE: Trauma-informed treatment increasingly is recognized as an important
      component of service delivery. This study examined differences in treatment
      related characteristics of facilities that offer moderate or high levels of
      trauma-informed counseling versus those that offer no or low levels of such
      counseling. METHODS: Responses from 13,223 substance abuse treatment facilities
      surveyed in 2009 by the National Survey of Substance Abuse Treatment Services
      (NSSATS) were used. RESULTS: A majority (66.6%) of facilities reported using
      trauma counseling sometimes or always or often. Facilities that provided moderate
      or high levels of trauma counseling were more likely to provide additional
      treatment services, such as disease testing and specialized group therapy, as
      well as child care, employment counseling, and other ancillary services.
      CONCLUSIONS: A majority of facilities reported provision of trauma counseling.
      Additional training and resources may be needed for programs that reported low
      rates of trauma counseling.

PMID- 22476308
TI  - Programs promote ill effects for offspring?

PMID- 22476310
TI  - Fountain house and recovery centers.

PMID- 22476312
TI  - The health literacy of adults with severe mental illness.

PMID- 22476318
TI  - NASMHPD initiative to strengthen role of SBHAs in state health care reform.

PMID- 22476320
TI  - Regulation of TLR4, p38 MAPkinase, IkappaB and miRNAs by inactivated strains of
      lactobacilli in human dendritic cells.
AB  - Strain specific properties of probiotics in providing supportive health effects
      in the immune system and the gastrointestinal tract have been widely investigated
      in vivo and in vitro. However, the underlying responsible mechanism is poorly
      described. By unravelling the probiotic-induced responses in a complex network of
      interacting signalling pathways, we investigated the effect of heat-inactivated
      Lactobacillus rhamnosus GG (LGG) and Lactobacillus delbrueckii subsp. bulgaricus
      (L.del) on the expression of TLR4 and signalling factors such as p38 MAPK and I?B
      at transcription level in human monocyte-derived dendritic cells (DCs). Our
      findings demonstrated that even inactivated probiotic strains can affect TLR4
      expression in a down-regulatory direction as with lipopolysaccharides after 12
      hours. LGG significantly down-regulated expression of p38 while I?B expression
      was significantly reduced in L.del-treated DCs. Moreover, we found these
      Lactobacillus strains could even modify the immune response at post
      transcriptional level by modifying miRNAs expression. Based on our results LGG
      induced a significant down-regulatory effect on miR-146a expression which is
      known as a novel fine negative regulator of immune response targeting NFkappaB.
      On the other hand, miR-155 was up-regulated by LGG which is consistent with down
      regulation of p38 and in LGG-treated DCs. These findings provide genetic and
      epigenetic explanations for the responsible underlying mechanisms by which
      probiotics influence immune response by targeting DCs.

PMID- 22476321
TI  - Oral consumption of potential probiotic Saccharomyces boulardii strain Unique 28
      in patients with acute diarrhoea: a clinical report.
AB  - This study was conducted to evaluate the efficacy and safety of Saccharomyces
      boulardii strain Unique 28 in patients suffering from acute diarrhoea. A total of
      25 patients (average age 30.72+/-4.38 years) with symptoms of acute diarrhoea
      (>=3 loose motion in last 24 hours for <7 days) were included upon informed
      consent and ethical committee approval. All subjects were assigned to consume S.
      boulardii strain Unique 28 (5*109 cfu/capsule) twice a day for a duration of 10
      days. Primary outcome measures such as duration of diarrhoea, frequency of
      defaecation, abdominal pain and consistency of stool were analysed on day 1, 3, 6
      and 10 of the study. Secondary outcome measures were evaluated by assessment of
      incidence and type of adverse events (blood pressure and pulse rate), physical
      examination and clinical laboratory tests (complete blood count, glutamic-pyruvic
      transaminase, serum creatinine, stool examination and microscopy and these tests
      were performed on day 1 and 10 of the study. The results of the present study
      indicate that the mean duration of diarrhoea decreased from 34.20+/-4.25 to
      9.40+/-3.00 (P<0.0001) min per day, frequency of defaecation decreased from
      7.04+/-0.84 to 1.76+/-0.52 (P<0.0001) times a day, abdominal pain decreased from
      3.28+/-1.06 (severe) to 0.72+/-0.50 (absent) (P<0.0001) and consistency of stool
      improved from 3.80+/-0.50 (watery) to 1.32+/-0.47 (soft) (P<0.0001). In addition,
      no significant changes in safety parameters were observed during treatment.
      Therefore, the present study concludes that S. boulardii strain Unique-28 might
      be useful in alleviating the symptoms of diarrhoea without any adverse effects.

PMID- 22476322
TI  - Transfer of antibiotic resistance determinants between lactobacilli isolates from
      the gastrointestinal tract of chicken.
AB  - The aim of this study was to assess the potential horizontal transfer of genetic
      traits for antibiotic resistance between lactobacilli isolated from the chicken
      gut, both in vitro and in vivo. Thirty-seven Lactobacillus spp. strains isolated
      from the gizzard, small and large intestines and caeca of free-range broiler
      chickens showed multi-drug resistance as assessed by disc diffusion assays. The
      minimum inhibitory concentration (MIC) for vancomycin, tetracycline, erythromycin
      and chloramphenicol was determined in De Man, Rogosa and Sharpe broth in a
      microplate assay. Almost all the lactobacilli isolates were resistant to
      vancomycin (except strains belonging to the Lactobacillus acidophilus group) and
      to tetracycline (MIC>=128 MUg/ml). Only five strains were resistant to
      erythromycin, and six to chloramphenicol. The transfer rate in filter mating
      experiments performed using L. acidophilus strain 4M14E (EmR), Lactobacillus
      vaginalis strain 5M14E (CmR), Lactobacillus salivarius strain 5C14C (EmR), and
      the 4G14L and 3C14C strains of Lactobacillus reuteri (CmR) showed a frequency of
      approximately 1*104 cfu/ml of double-resistant transconjugants for the different
      combinations. The exception was the L. salivarius 5C14C (EmR) and L. vaginalis
      5M14E (CmR) mating combination, which produced no transconjugants. In vivo
      experiments performed in gnotobiotic mice by mating L. acidophilus 4M14E (EmR)
      with L. reuteri 3C14C (CmR), L. reuteri 4G14L (CmR) or L. vaginalis 5M14E (CmR)
      resulted in transconjugants at 3.95+/-0.29, 3.16+/-0.33, and 4.55+/-1.52 log10
      cfu/g of faeces, respectively. Taken together, these data suggest that genetic
      exchange may occur between native bacterial strains within the gastrointestinal
      tract of chickens, which might maintain a dynamic gene pool conferring antibiotic
      resistance upon indigenous microbiota components, even in the absence of the
      pathogens. This possibility must be taken into account as a complementary
      criterion when lactobacilli are screened for probiotic use.

PMID- 22476323
TI  - Reversible water uptake by a stable imine-based porous organic cage.
AB  - A crystalline porous organic cage molecule, CC3, is shown to adsorb up to 20.1
      wt% water reversibly. This was confirmed by both gravimetric sorption and by
      crystallographic analysis. Crystals of CC3 are stable in boiling water for at
      least 4 h. The surprising chemical and supramolecular stability of these imine
      based molecular crystals suggests scope for practical applications in humid
      environments.

PMID- 22476324
TI  - Curcumin differentially regulates the expression of superoxide dismutase in
      cerebral cortex and cerebellum of L-thyroxine (T4)-induced hyperthyroid rat
      brain.
AB  - The present investigation was aimed to elucidate the effect of curcumin on lipid
      peroxidation (LPx) and superoxide dismutase (SOD) in L-thyroxine (T4)-induced
      oxidative stress in cerebral cortex and cerebellum of rat brain. Elevated level
      of LPx in cerebral cortex declined to control level on supplementation of
      curcumin to T4-treated rats. On the other hand, unaltered LPx level in T4-treated
      rats showed a significantly decreased level of LPx on supplementation of
      curcumin. The increased activity of SOD and translated products of SOD1 and SOD2
      in cerebral cortex of T4-treated rats was ameliorated on supplementation of
      curcumin. The decreased activity of SOD and protein expression of SOD1 in
      cerebellum of T4-treated rats were ameliorated on administration of curcumin. On
      the other hand, SOD2 expression was not influenced either by T4-treated or by
      curcumin supplementation to T4-treated rats. Results of the present investigation
      reveal that the regulation of expression of SOD by curcumin in different regions
      (cerebral cortex and cerebellum) of rat brain is different under hyperthyroidism.

PMID- 22476325
TI  - Ultrastructural and cytochemical studies on oogenesis of the fern Pteridium
      aquilinum.
AB  - Egg development in Pteridium aquilinum var. latiusculum was studied using
      ultrastructural and cytochemical methods to examine structural features
      influencing fertilization in leptosporangiate ferns. Ultrastructural observations
      indicate a separation cavity is first formed above the egg during oogenesis with
      a pore region persistently connecting the egg and the ventral canal cell. The egg
      envelope is formed by deposition of amorphous materials in the separation cavity
      on the outer surface of plasmalemma. The egg envelope was not formed across the
      pore region; instead, a fertilization pore was formed. During oogenesis, the egg
      nucleus produced extensive evaginations containing osmiophilic bodies.
      Cytochemical experiments revealed that the egg envelope displays strong periodic
      acid-Schiff reaction indicative of polysaccharides, with negligible Sudan black B
      staining for lipids, suggesting that the egg envelope is composed principally of
      polysaccharides, and not lipids. The present manuscript provides new insights
      into egg structure and development of Pteridium, including discovery and
      characterization of the fertilization pore and observations on the chemical
      nature of the egg envelope, thus contributing to the understanding of the
      cytological mechanism of the sexual reproduction of ferns.

PMID- 22476326
TI  - Morphological, histological and ultrastructural changes in the olive pistil
      during flowering.
AB  - Sexual reproduction is essential for the propagation of higher plants. From an
      agronomical point of view, this is a particularly key process because
      fertilization guarantees fruit formation in most cultivated fruit species. In the
      olive, however, in spite of its agricultural importance, little attention has
      been paid to the study of sexual reproduction. In order to investigate the
      cellular and molecular mechanisms that regulate pollen-pistil interactions in the
      olive during the progamic phase, it is essential to first have a good knowledge
      of the reproductive structures involved in such interactions. This study
      characterizes the anatomical and ultrastructural changes in the olive pistil,
      beginning from the young pistil developing within the bud until the time of petal
      loss and visible stigma senescence. We have correlated changes in the pistil with
      a series of defined floral developmental stages and determined that olive pistil
      structures cannot be considered completely mature and ready to be pollinated and
      fertilized until the onset of anthesis. Our results clearly show histological and
      ultrastructural variation during the diverse flowering events. We discuss whether
      the changes observed might influence or result from pollen-pistil interactions
      during the progamic phase.

PMID- 22476327
TI  - Control charts in healthcare quality improvement. A systematic review on
      adherence to methodological criteria.
AB  - OBJECTIVES: Use of Shewhart control charts in quality improvement (QI)
      initiatives is increasing. These charts are typically used in one or more phases
      of the Plan Do Study Act (PDSA) cycle to monitor summaries of process and outcome
      data, abstracted from clinical information systems, over time. We summarize
      methodological criteria of Shewhart control charts and investigate adherence of
      published QI studies to these criteria. METHODS: We searched Medline, Embase and
      CINAHL for studies using Shewhart control charts in QI processes in direct
      patient care. We extracted methodological criteria for Shewhart control charts,
      and for the use of these charts in PDSA cycles, from textbooks and methodological
      literature. RESULTS: We included 34 studies, presenting 64 control charts of
      which 40 control charts plotted two phases of the PDSA cycle. The criterion to
      use 10-35 data points in a control chart was least adhered to (48.4% non
      adherence). Other criteria were: transformation of the data in case of a skewed
      distribution (43.7% non adherence), when comparing data from two phases of the
      PDSA cycle the Plan phase (the first phase) needs to be stable (40.0% non
      adherence), using a maximum of four different rules to detect special cause
      variation (14.1% non-adherence), and setting control limits at three standard
      deviations from the mean (all control charts adhered). CONCLUSION: There is room
      for improvement with regard to the methodological construction of Shewhart
      control charts used in QI processes. Higher adherence to all methodological
      criteria will decrease the risk of incorrect conclusions about the process being
      monitored.

PMID- 22476328
TI  - Leadership in medical emergencies is not gender specific.

PMID- 22476330
TI  - Code reader: a novel concept that warrants more research.

PMID- 22476332
TI  - Influence of cheese matrix on lipid digestion in a simulated gastro-intestinal
      environment.
AB  - Foods are complex nutrient assemblies which are subjected to various industrial
      processes that can influence their nutritional value. The food matrix acts as a
      nutrient-release regulator, and further understanding of its behavior during
      digestion is essential. The objective of this study was to compare the kinetics
      of matrix degradation and fatty acids release for different cheeses in a gastro
      intestinal environment. The relationship between the physical characteristics of
      the cheeses (rheological properties, microstructure) and their digestion pattern
      was also studied. Rheological measurements, compositional and microstructure
      analyses were performed on mild Cheddar, aged Cheddar, light Cheddar and
      Mozzarella cheeses. Cheese samples were subjected to simulated digestion. Matrix
      degradation index, free oil, free fatty acids and fat droplet distribution were
      analyzed after 5, 30, 60, 120, 150, 180 and 240 min of digestion. Mozzarella
      cheese showed the highest rate of matrix degradation, free oil and fatty acids
      release. Aged Cheddar cheese showed rapid degradation during the gastric phase,
      but was more resistant to the duodenal environment. Light Cheddar showed the
      opposite behavior, being highly resistant to the gastric environment; however, it
      underwent extensive degradation at the end of the duodenal phase. The extent of
      matrix degradation for mild Cheddar was similar to that of Mozzarella in the
      gastric phase but was much lower than that of other cheeses in the duodenal
      phase. The cheeses under study exhibited very different digestion patterns, and
      these differences are discussed in relation to cheese matrix composition,
      microstructure and rheological properties. Results suggest that cheese
      degradation and kinetics of fatty acids release are mainly driven by cheese
      physical characteristics.

PMID- 22476333
TI  - Preoperative assessment of peritoneal carcinomatosis: intraindividual comparison
      of 18F-FDG PET/CT and MRI.
AB  - OBJECTIVE: Exact determination of localization and extent of peritoneal
      carcinomatosis (PC) before peritonectomy and hyperthermic intraperitoneal
      chemotherapy (HIPEC) is crucial for the clinical outcome. Our study compares
      dynamic contrast enhanced 3D MRI (T1wDCE) and 18F-FDG PET/CT regarding diagnostic
      accuracy in correlation with surgical exploration (SE) and histological (HI)
      results. MATERIALS AND METHODS: 15 patients with PC were examined on a 1.5T MRI
      and 16 slice PET/CT. MRI: coronal T1wDCE covering the complete abdomen (0.15 mmol
      Gd-chelate/kg BW, 2000 mL mannitol solution p.o., 40 mg buscopan i.v.). PET-CT:
      contrast enhanced 16slice CT (120 mL ultravist 370 i.v., 1000 mL mannitol
      solution p.o., 40 mg buscopan i.v.), PET: 350 MBq 18-FDG i.v., 3 min acquisition
      time/bed, 60 min after tracer injektion). Assessment by two independent,
      experienced observers in correlation with results of SE and HI for each abdominal
      segment based on the peritoneal cancer index (PCI) proposed by Sugarbaker and co
      authors. RESULTS: MRI and PET/CT provided reliable detection of PC. One patient
      had to be excluded from statistical analysis. In summary, 182 segments were
      assessed (13/patient, 14 patients, one patient excluded from statistical
      analysis). PC was found in 118 by MRI, 124 by PET/CT. 4 segments were classified
      false positive for MRI, 2 for PET/CT. False negative segments (MRI: 17, PET/CT:
      9) did not result in irresectability. Positive predictive value for PC/segment
      was 97/98%, negative predictive value 73/84%, sensitivity 87/93%, specificity
      92/96%, and diagnostic accuracy 88/94% (MRI/PET/CT). CONCLUSION: With high
      diagnostic accuracy for PC of both, MRI and PET/CT, PET/CT provides better
      diagnostic accuracy and especially better NPV.

PMID- 22476334
TI  - Insight into Crohn's disease pathomorphology.
AB  - Crohn's disease (CD) belongs together with ulcerative colitis to the two major
      forms of inflammatory bowel diseases (IBD). Although its etiology remains poorly
      understood, several genetic and immune factors and cells (especially T cells)
      have been shown to be involved in the pathogenesis of IBD. Among these factors,
      proinflammatory T cells and their secreted cytokines seem to be the main
      effectors in induction and perpetuation of the intestinal inflammation. Beside
      the local inflammatory effect, there is a very clear defined mechanism where T
      cells and inflammatory complexes migrate and induce extraintestinal manifestation
      and complications. This article reviews current knowledge of the pathomorphology
      of mucosal inflammation in CD focusing especially on the immune mechanisms of T
      cell homing, extraintestinal manifestations and fibrogenesis.

PMID- 22476335
TI  - Spigelian hernia: CT findings and clinical relevance.
AB  - OBJECTIVE: The purpose of our study was to evaluate the clinical relevance of
      preoperative CT in distinguishing between the two subtypes of spigelian hernia
      (SH). MATERIALS AND METHODS: We reviewed retrospectively the CT images of 35
      patients. The patients were divided into two groups on the basis of the SH
      subtype: interstitial SH group (n = 15) and subcutaneous SH group (n = 20).
      Clinical characteristics of patients and CT findings were analyzed. Bowel
      ischemia on surgery was also noted. RESULTS: Sixteen right hernias and 19 left
      hernias were observed. Fifteen interstitial SH (43%) and 20 subcutaneous SH (57%)
      were found. No type of content showed a statistically significant association
      with one or other subtype of SH. Nine of the 26 patients presenting with SH with
      SB content showed signs of SBO on CT. Closed-loop SBO on CT was present in 5 of
      the 26 patients with SB content. An interstitial SH was observed in all of these
      5 patients (p = 0.039). Surgery was performed on 10 patients. Bowel ischemia was
      found on surgery in 4 patients and showed no statistically significant
      association with a particular subtype of SH (p = 0.6). CONCLUSION: Our study
      shows the importance of performing CT in SH. CT provides the diagnosis of SH,
      shows SH content, and demonstrates the presence of SBO or closed-loop SBO.
      Moreover, the distinction between the two subtypes of SH on CT appears to be of
      clinical relevance since closed-loop SBO is statistically associated with
      interstitial SH and the optimal surgical approach may differ.

PMID- 22476337
TI  - [Implant removal].

PMID- 22476338
TI  - [Removal of plates and screws. Tips and tricks for problematic cases].
AB  - BACKGROUND: This overview article addresses the different ways of explanting
      plates and screws. Once the decision has been taken to remove plates and screws,
      the situation is resolved by skilled performance of surgical procedures. METHOD:
      In particular, tips and tricks are offered on how to deal with difficult
      explantations. In general, implant removal is straightforward and without
      complications. Special techniques, instruments, tips and tricks are important
      when implant removal becomes problematic due to screw damage, immovable implants,
      instrument breakage and suchlike. CONCLUSION: This article describes procedures
      that will put the surgeon on a direct route to implant removal. Keeping strictly
      to the pathway will inevitably turn problematic implant removal into a
      straightforward procedure.

PMID- 22476339
TI  - [Implant removal after intramedullary osteosyntheses. Literature review,
      technical details, and tips and tricks].
AB  - We present a literature review about implant removal after intramedullary
      stabilization of femoral or tibial shaft fractures, upper extremity fractures,
      and pediatric fractures. A special focus is the difficult implant removal.
      Implant removal of nails gets difficult when implants are bent or broken. Other
      difficulties include broken interfaces between nail and removal instrument or
      when bone ingrowth hinders extraction. A special difficulty is posed by broken
      solid nails. Implant failure shows typical failure patterns regarding the
      location of the fatigue fracture. Based on well-documented clinical cases, we
      describe in detail surgical techniques as well as tips and tricks which help in
      the difficult circumstances of bent or broken implants in proximal, midshaft, or
      distal nail segments for a large variety of implants (solid, cannulated,
      slotted). We also describe an elegant technique for the safe removal of an
      infected cemented arthrodesis nail. The time required to perform a nail removal
      can easily exceed the planned amount. Nail removal can result in significant
      complications like soft tissue damage, fractures, infections, and other problems.
      Not only because of these problems, the decision on whether or not to remove the
      nail should be made with great care. Therefore, good communication with the
      patient and thorough information about risks and benefits are essential.

PMID- 22476340
TI  - [Is routine implant removal after trauma surgery sensible?].
AB  - We present a literature review about implant removal after operative extremity
      and spine fracture treatment. The indication for implant removal procedures has
      become less frequent in recent years, but is still more common in Europe than for
      example in North America. The time required to perform a implant removal can
      easily exceed the planned amount. Implant removal can result in significant
      complications like soft tissue damage, fractures, infections, and other problems.
      Not only because of these problems, the decision on whether or not to remove the
      implant should be made with great care. Therefore good communication with the
      patient and thorough information about risks and benefits are essential.

PMID- 22476341
TI  - [Refracture of long bones after implant removal. An avoidable complication?].
AB  - Refractures of long bones after implant removal are a rare but serious
      complication, which in most cases make a reoperation necessary. We analysed our
      own cases and reviewed the scarce literature on this subject. As a result we
      found that it is possible to reduce this complication by performing thorough
      preoperative preparation, observing an adequate interim time between initial
      osteosynthesis and hardware removal, cautiously exposing the weakened bone to
      force for a certain time period after implant removal and taking the character of
      the fracture healing into consideration. It is not possible to entirely eradicate
      this complication because a lot of patients demand the implant removal even
      though it is known that demineralisation and residual screw holes both induce a
      reduction of energy-absorbing capacity and therefore predispose the patient to
      refracture. In some cases the surgeon should recommend that the implants remain
      in situ.

PMID- 22476343
TI  - [Hardware removal after spinal instrumentation].
AB  - Because of the increasing number of patients with surgically treated injuries of
      the spine we more often have to answer the question of indication for hardware
      removal. In the cervical spine and after anterior instrumentations of the
      thoracic and lumbar spine hardware removal is only indicated as part of the
      management of postoperative complications. After dorsal instrumentation for
      fractures of the thoracic and lumbar spine, implant-associated discomfort is
      possible. In addition, in non-fusion procedures there is the risk of implant
      failure. In these cases the hardware should be removed. If the consolidation of
      the fracture is in doubt, a preoperative CT scan is useful.

PMID- 22476342
TI  - [Hardware removal after pelvic ring injury].
AB  - BACKGROUND: Pelvic ring fractures are considered as rare injuries. Minimally
      invasive sacroiliac screw fixation has been used increasingly in recent years as
      an operative strategy for the treatment of these injuries, if the dorsal pelvic
      ring needed to be addressed. Treatment options for the anterior pelvic ring
      comprise plates, screws or external fixation. METHOD: Based on the limited number
      of publications on this subject and our own experience with 80 patients who
      suffered pelvic ring B- or C-type injuries during a period of 8 years we are able
      to show that the indication for hardware removal in the pelvic ring should be
      strictly defined. RESULTS: In some cases like external fixation, implant
      associated infection, malpositioning, allergic implant reaction, critical soft
      tissue covering, palpable hardware and consolidated juvenile fractures implant
      removal is certainly indicated. In patients without symptoms and in patients with
      trauma-associated symptoms which are not definitely associated with the hardware,
      the removal should be only indicated after thorough consideration of the risks
      versus the benefits and additionally by taking the initial injury pattern into
      account. If despite all these objections the hardware removal has been indicated
      it should always be considered that hardware removal may be challenging with
      several possible severe complications.

PMID- 22476344
TI  - [Principles of perioperative coagulation management].
AB  - The coagulation system is a complex network of interacting proteins and cells
      with extensive sensitivity, amplification and control pathways. The system
      represents a delicate balance between procoagulant and anticoagulant as well as
      profibrinolytic and antifibrinolytic activities. Clinically relevant phenotypes,
      e.g. bleeding and thrombosis, occur immediately when this balance is no longer in
      equilibrium. A correct understanding of the complex coagulation pathophysiology
      in the perioperative setting is essential for an effective treatment. In a
      bleeding patient, patient's history, clinical findings, routine and advanced
      laboratory coagulation testing as well as point-of-care coagulation monitoring
      help to reliably and readily identify the underlying coagulation disorder. Modern
      coagulation management is proactive, individualized, balanced and follows clearly
      defined algorithms. Coagulopathic bleeding can be successfully controlled with
      specific interventions in the coagulation system.

PMID- 22476346
TI  - Expedient chemical synthesis of 75mer DNA binding domain of MafA: an insight on
      its binding to insulin enhancer.
AB  - An expedient chemical synthesis of a 75mer peptide corresponding to the DNA
      binding domain (DBD, 227-301) of the human MafA leucine zipper transcription
      factor is reported. The application of microwave-assisted solid phase peptide
      synthesis (MW-SPPS) with a protocol modified respect to the standard one allowed
      obtaining the desired 75mer peptide in a short time with high quantity and
      optimal purity. MW-SPPS methodology was thus demonstrated as a valuable
      alternative to recombinant methods to obtain protein domains. Considering that
      recent findings suggest an involvement of MafA in the pathogenesis of diabetes
      mellitus, we also performed circular dichroism studies both on DBD folding and
      its interaction with MafA recognition element (MARE) on insulin enhancer. From
      our results, it was evicted that a disorder to order transition occurs after DBD
      interaction with insulin MARE which is mediated by specific structural elements
      on the N-terminus of the DBD.

PMID- 22476345
TI  - Taurine deficiency damages retinal neurones: cone photoreceptors and retinal
      ganglion cells.
AB  - In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in
      cats and rats. Recently, we found that taurine deficiency contributes to the
      retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity,
      retinal ganglion cells were degenerating in parallel to cone photoreceptors. The
      aim of this study was to re-assess a classic mouse model of taurine deficiency
      following a treatment with guanidoethane sulfonate (GES), a taurine transporter
      inhibitor to determine whether retinal ganglion cells are also affected. GES
      treatment induced a significant reduction in the taurine plasma levels and a
      lower weight increase. At the functional level, photopic electroretinograms were
      reduced indicating a dysfunction in the cone pathway. A change in the
      autofluorescence appearance of the eye fundus was explained on histological
      sections by an increased autofluorescence of the retinal pigment epithelium.
      Although the general morphology of the retina was not affected, cell damages were
      indicated by the general increase in glial fibrillary acidic protein expression.
      When cell quantification was achieved on retinal sections, the number of
      outer/inner segments of cone photoreceptors was reduced (20 %) as the number of
      retinal ganglion cells (19 %). An abnormal synaptic plasticity of rod bipolar
      cell dendrites was also observed in GES-treated mice. These results indicate that
      taurine deficiency can not only lead to photoreceptor degeneration but also to
      retinal ganglion cell loss. Cone photoreceptors and retinal ganglion cells appear
      as the most sensitive cells to taurine deficiency. These results may explain the
      recent therapeutic interest of taurine in retinal degenerative pathologies.

PMID- 22476348
TI  - Development and application of site-specific proteomic approach for study protein
      S-nitrosylation.
AB  - Protein S-nitrosylation is the covalent redox-related modification of cysteine
      sulfhydryl groups with nitric oxide, creating a regulatory impact similar to
      phosphorylation. Recent studies have reported a growing number of proteins to be
      S-nitrosylated in vivo resulting in altered functions. These studies support S
      nitrosylation as a critical regulatory mechanism, fine-tuning protein activities
      within diverse cellular processes and biochemical pathways. In addition, S
      nitrosylation appears to have key roles in the etiology of a broad range of human
      diseases. In this review, we discuss recent advances in proteomic approaches for
      the enrichment, identification, and quantitation of cysteine S-nitrosylated
      proteins and peptides. These advances have provided analytical tools with the
      power to interpret the impact of S-nitrosylation at the system level, providing a
      new platform for drug discovery and the identification of diagnostic markers for
      human diseases.

PMID- 22476347
TI  - EBP50 inhibits EGF-induced breast cancer cell proliferation by blocking EGFR
      phosphorylation.
AB  - Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) suppresses breast cancer
      cell proliferation, potentially through its regulatory effect on epidermal growth
      factor receptor (EGFR) signaling, although the mechanism by which this occurs
      remains unknown. Thus in our studies, we aimed to determine the effect of EBP50
      expression on EGF-induced cell proliferation and activation of EGFR signaling in
      the breast cancer cell lines, MDA-MB-231 and MCF-7. In MDA-MB-231 cells, which
      express low levels of EBP50, EBP50 overexpression inhibited EGF-induced cell
      proliferation, ERK1/2 and AKT phosphorylation. In MCF-7 cells, which express high
      levels of EBP50, EBP50 knockdown promoted EGF-induced cell proliferation, ERK1/2
      and AKT phosphorylation. Knockdown of EBP50 in EBP50-overexpressed MDA-MB-231
      cells abrogated the inhibitory effect of EBP50 on EGF-stimulated ERK1/2
      phosphorylation and restoration of EBP50 expression in EBP50-knockdown MCF-7
      cells rescued the inhibition of EBP50 on EGF-stimulated ERK1/2 phosphorylation,
      further confirming that the activation of EGF-induced downstream molecules could
      be specifically inhibited by EBP50 expression. Since EGFR signaling was triggered
      by EGF ligands via EGFR phosphorylation, we further detected the phosphorylation
      status of EGFR in the presence or absence of EBP50 expression. Overexpression of
      EBP50 in MDA-MB-231 cells inhibited EGF-stimulated EGFR phosphorylation, whereas
      knockdown of EBP50 in MCF-7 cells enhanced EGF-stimulated EGFR phosphorylation.
      Meanwhile, total expression levels of EGFR were unaffected during EGF
      stimulation. Taken together, our data shows that EBP50 can suppress EGF-induced
      proliferation of breast cancer cells by inhibiting EGFR phosphorylation and
      blocking EGFR downstream signaling in breast cancer cells. These results provide
      further insight into the molecular mechanism by which EBP50 regulates the
      development and progression of breast cancer.

PMID- 22476349
TI  - Amazon forest fires between 2001 and 2006 and birth weight in Porto Velho.
AB  - Birth weight data (22,012 live-births) from a public hospital in Porto Velho
      (Amazon) was used in multiple statistical models to assess the effects of forest
      fire smoke on human reproductive outcome. Mean birth weights for girls (3,139 g)
      and boys (3,393 g) were considered statistically different (p-value < 2.2e-16).
      Among all models analyzed, the means were considered statistically different only
      when treated as a function of month and year (p-value = 0.0989, girls and 0.0079,
      boys) . The R (2) statistics indicate that the regression models considered are
      able to explain 65 % (girls) and 54 % (boys) of the variation of the mean birth
      weight.

PMID- 22476350
TI  - Decrease of herbicide bromobutide and its debromo metabolite in paddy field soil
      during 24 weeks after application.
AB  - Variations in concentrations of herbicide bromobutide (RS)-2-bromo-N-(alpha,alpha
      dimethylbenzyl)-3,3-dimethylbutyramide, and its metabolite bromobutide-debromo, N
      (alpha,alpha-dimethylbenzyl)-3,3-dimethylbutyramide were investigated in soils
      from three paddy fields used for rice farming at 24 weeks after application. The
      bromobutide concentration was maximum within 24 h after application. That of
      bromobutide-debromo was maximum within 5-7 days of application. Each gradually
      decreased to below detection limits at 12-22 weeks after application. Bromobutide
      was detected up to 76-104 days after application in the paddy soils, whereas
      bromobutide-debromo was detected up to 125 days after application. The
      bromobutide composition was higher than 90 % within 6 days of application,
      decreasing to less than 5 % by 125 days of application. The decrease of
      bromobutide amount in the soil was inferred as the first-order reaction. The
      bromobutide half-life was calculated as 12-21 days (16 days mean) during 18-104
      days following application.

PMID- 22476351
TI  - Arterial microcalcification in atherosclerotic patients with and without chronic
      kidney disease: a comparative high-resolution scanning X-ray diffraction
      analysis.
AB  - Vascular calcification, albeit heterogeneous in terms of biological and
      physicochemical properties, has been associated with ageing, lifestyle, diabetes,
      and chronic kidney disease (CKD). It is unknown whether or not moderately
      impaired renal function (CKD stages 2-4) affects the physiochemical composition
      and/or the formation of magnesium-containing tricalcium phosphate
      ([Ca,Mg](3)[PO(4)](2), whitlockite) in arterial microcalcification. Therefore, a
      high-resolution scanning X-ray diffraction analysis (European Synchrotron
      Radiation Facility, Grenoble, France) utilizing histological sections of paraffin
      embedded arterial specimens derived from atherosclerotic patients with normal
      renal function (n = 15) and CKD (stages 2-4, n = 13) was performed. This approach
      allowed us to spatially assess the contribution of calcium phosphate (apatite)
      and whitlockite to arterial microcalcification. Per group, the number of samples
      (13 vs. 12) with sufficient signal intensity and total lengths of regions (201
      vs. 232 MUm) giving rise to diffractograms ("informative regions") were
      comparable. Summarizing all informative regions per group into one composite
      sample revealed calcium phosphate/apatite as the leading mineral phase in CKD
      patients, whereas in patients with normal renal function the relative
      contribution of whitlockite and calcium phosphate/apatite was on the same order
      of magnitude (CKD, calcium phosphate/apatite 157 MUm, whitlockite 38.7 MUm; non
      CKD, calcium phosphate/apatite 79.0 MUm, whitlockite 94.1 MUm; each p < 0.05).
      Our results, although based on a limited number of samples, indicate that chronic
      impairment of renal function affects local magnesium homeostasis and thus
      contributes to the physicochemical composition of microcalcification in
      atherosclerotic patients.

PMID- 22476352
TI  - Studying the effect of the psychosocial work environment on risk of ill-health:
      towards a more comprehensive assessment of working conditions.

PMID- 22476353
TI  - The potential prognostic value of cathepsin D protein in serous ovarian cancer.
AB  - OBJECTIVES: Overexpression of a ubiquitous lysosomal aspartyl protease cathepsin
      D (cath-D) is involved in the progression of certain cancer types. This study
      investigated the prognostic value of the cath-D expression and its association
      with other known clinicopathological parameters in serous ovarian carcinoma.
      MATERIALS AND METHODS: Cath-D was detected by immunohistochemistry in 49 serous
      ovarian carcinomas and compared to 50 benign serous ovarian tumors. The results
      were correlated with clinicopathological characteristics and survival outcomes.
      RESULTS: In both cath-D positive benign and malignant serous ovarian tumors, a
      specific granular cytoplasmic staining was observed in both epithelial and
      stromal cells. Cath-D expression levels were higher in serous ovarian carcinomas
      than in benign tumors (P < 0.01). Cath-D expression in tumor epithelial cells
      correlated with mesenchymal cell expression (P < 0.001). The cath-D expression
      levels of tumor epithelial cells correlated with residual tumor size (P = 0.027)
      and was not related to other factors (P > 0.05). Patients with higher cath-D
      expression in epithelial cells had longer disease-free survival time (DFST; P =
      0.025) and overall survival time (OST; P = 0.030). Through the Cox regression
      test, we found that the response to treatment (P < 0.001), pathological stage (P
      < 0.001), and peritoneal cytology results (P = 0.018) were independent effect
      factors for DFST. The expression level of cath-D in epithelial cells (P = 0.025),
      response to treatment (P < 0.001), pathological stage (P = 0.001), and peritoneal
      cytology results (P = 0.002) were independent effect factors for OST. CONCLUSION:
      This showed that cath-D was an indicator of malignancy in serous ovarian
      carcinoma. It was expressed more highly in serous ovarian carcinoma than benign
      serous ovarian tumor. Additionally, our results suggested that high expression of
      cath-D in tumor epithelial cells was a favorable survival prognostic factor for
      serous ovarian carcinoma.

PMID- 22476354
TI  - Particle-size distributions and seasonal diversity of allergenic and pathogenic
      fungi in outdoor air.
AB  - Fungi are ubiquitous in outdoor air, and their concentration, aerodynamic
      diameters and taxonomic composition have potentially important implications for
      human health. Although exposure to fungal allergens is considered a strong risk
      factor for asthma prevalence and severity, limitations in tracking fungal
      diversity in air have thus far prevented a clear understanding of their human
      pathogenic properties. This study used a cascade impactor for sampling, and
      quantitative real-time PCR plus 454 pyrosequencing for analysis to investigate
      seasonal, size-resolved fungal communities in outdoor air in an urban setting in
      the northeastern United States. From the 20 libraries produced with an average of
      ~800 internal transcribed spacer (ITS) sequences (total 15 326 reads), 12 864 and
      11 280 sequences were determined to the genus and species levels, respectively,
      and 558 different genera and 1172 different species were identified, including
      allergens and infectious pathogens. These analyses revealed strong relationships
      between fungal aerodynamic diameters and features of taxonomic compositions. The
      relative abundance of airborne allergenic fungi ranged from 2.8% to 10.7% of
      total airborne fungal taxa, peaked in the fall, and increased with increasing
      aerodynamic diameter. Fungi that can cause invasive fungal infections peaked in
      the spring, comprised 0.1-1.6% of fungal taxa and typically increased in relative
      abundance with decreasing aerodynamic diameter. Atmospheric fungal ecology is a
      strong function of aerodynamic diameter, whereby through physical processes, the
      size influences the diversity of airborne fungi that deposit in human airways and
      the efficiencies with which specific groups of fungi partition from outdoor air
      to indoor environments.

PMID- 22476355
TI  - Comparison of primary total hip replacements performed with a direct anterior
      approach versus the standard lateral approach: perioperative findings.

PMID- 22476356
TI  - A classification method for neurogenic heterotopic ossification of the hip.
AB  - BACKGROUND: Existing classifications for heterotopic ossification (HO) do not
      include all HO types; nor do they consider the anatomy of the involved joint or
      the neurological injury. Therefore, we performed this study to propose and
      evaluate a classification according to the location of neurogenic HO and the
      neurological injury. MATERIALS AND METHODS: We studied the files of 24
      patients/33 hips with brain or spinal cord injury and neurogenic HO of the hip
      treated with excision, indomethacin, and radiation therapy. We classified
      patients according to the Brooker classification scheme as well as ours. Four
      types of neurogenic HO were distinguished according to the anatomical location of
      HO: type 1, anterior; type 2, posterior; type 3, anteromedial; type 4,
      circumferential. Subtypes of each type were added based on the neurological
      injury: a, spinal cord; b, brain injury. Mean follow-up was 2.5 years (1-8
      years). RESULTS: The Brooker classification scheme was misleading-all hips were
      class III or IV, corresponding to ankylosis, even though only 14 hips had
      ankylosis. On the other hand, our classification was straightforward and easy to
      assign in all cases. It corresponded better to the location of the heterotopic
      bone, and allowed for preoperative planning of the appropriate surgical approach
      and evaluation of the prognosis; recurrence of neurogenic HO was significantly
      higher in patients with brain injury (subtype b), while blood loss was higher for
      patients with anteromedial (type 3) and circumferential (type 4) neurogenic HO.
      CONCLUSIONS: Our proposed classification may improve the management and
      evaluation of the prognosis for patients with neurogenic HO.

PMID- 22476357
TI  - Triple jeopardy: transscaphoid, transcapitate, transtriquetral, perilunate
      fracture dislocation.
AB  - Carpal injuries are frequently underdiagnosed and underreported injuries of the
      hand. Scapholunate perilunate dissociation is the most common perilunate
      instability pattern seen in clinical practice. Transscaphoid, transtriquetral,
      transcapitate dislocation with a volar intercalated segment instability pattern
      is a very rare pattern of carpal injury. We describe a case with this unique
      pattern of injury, explaining its mechanism and treatment. Good outcome can be
      achieved in these injuries following open reduction and internal fixation with
      ligamentous repair. 

PMID- 22476358
TI  - Search performance with discrete-cell stimulus arrays: filtered naturalistic
      images and probabilistic markers.
AB  - In order to partially fill the gap between search studies with artificial and
      naturalistic stimuli, experiments with segmented and spatially filtered images of
      real stimuli in the discrete cells of search arrays were conducted. RT * set size
      functions obtained with the spatially filtered arrays were compared with those
      obtained with geometric and other types of arrays. With the aid of Fourier
      analysis, components of target certainty/uncertainty, target-distractor
      similarity/dissimilarity, and distractor homogeneity/heterogeneity were evaluated
      for their effects on search performance and efficiency. The comparative effects
      of valid/invalid and ambiguous/unambiguous markers of search items were included
      in the experiments to probe the potential contributions of top-down and bottom-up
      control to search with naturalistic stimuli. Visual coding in the form of spatial
      frequency passbands and top-down preferences for distractor search were used to
      explain the results.

PMID- 22476359
TI  - Trends in U.S. Attitudes Toward Genetic Testing, 1990-2004.
AB  - This research note examines changes in beliefs and attitudes over a 14-year
      period, from 1990, when the revolution in genomic science was just beginning, to
      2004, the most recent time point for which data are available. The analysis makes
      clear that there is no simple causal path from changes in technology to changes
      in values and beliefs, at least over the period of time during which we have been
      able to track this process. At the same time, claimed awareness about the new
      technology is slowly and gradually diffusing throughout the society.

PMID- 22476360
TI  - [18F]-5-Fluoro-5-deoxyribose, an efficient peptide bioconjugation ligand for
      positron emission tomography (PET) imaging.
AB  - [(18)F]-5-Fluoro-5-deoxyribose ([(18)F]-FDR) conjugates much more rapidly than
      [(18)F]-FDG under mild reaction conditions to peptides and offers new prospects
      for mild and rapid bioconjugation for fluorine-18 labelling in PET imaging.

PMID- 22476361
TI  - Arthritis related to systemic meningococcal disease: 34 years' experience.
AB  - The purpose of this investigation was to assess the clinical characteristics,
      therapeutic aspects, and outcome of arthritis related to invasive meningococcal
      disease (IMD). All episodes of bacterial meningitis and IMD are recorded
      systematically. We selected all episodes of IMD, with or without meningitis, that
      presented arthritis. From 1977 to 2010, 522 episodes of IMD were treated. Thirty
      nine of these (7.5 %, 26 women, mean age 33 years) presented arthritis. Of these
      39, 37 (95 %) presented skin lesions and 31 (79 %) had meningitis. Twenty (51 %)
      had positive blood cultures and six (15 %) had shock. No differences were found
      in skin lesions, shock, or bacteremia compared to cases without arthritis. In
      contrast to other septic forms, arthritis related to IMD was cured with short
      antibiotic therapy and without surgical drainage. There was no mortality. All
      patients recovered and none presented joint sequelae; however, 13 adult patients
      (33 %) required long-term treatment with steroids due to persistent symptoms.
      Arthritis related to IMD most frequently affects the knees and ankles, and may be
      a cause of fever relapse. Short antibiotic therapy is enough in all cases and
      surgical drainage is not needed. In some adult patients, especially those over 50
      years of age, evolution is torpid and steroid therapy may be required in order to
      achieve recovery.

PMID- 22476362
TI  - Ambulatory orthopaedic surgery patients' knowledge with internet-based education.
AB  - BACKGROUND: There is a growing need for patient education and an evaluation of
      its outcomes. OBJECTIVES: The aim of this study was to compare ambulatory
      orthopaedic surgery patients' knowledge with Internet-based education and face-to
      face education with a nurse. The following hypothesis was proposed: Internet
      based patient education (experiment) is as effective as face-to-face education
      with a nurse (control) in increasing patients' level of knowledge and sufficiency
      of knowledge. In addition, the correlations of demographic variables were tested.
      METHODS: The patients were randomized to either an experiment group (n = 72) or a
      control group (n = 75). Empirical data were collected with two instruments.
      RESULTS: Patients in both groups showed improvement in their knowledge during
      their care. Patients in the experiment group improved their knowledge level
      significantly more in total than those patients in the control group. There were
      no differences in patients' sufficiency of knowledge between the groups.
      Knowledge was correlated especially with patients' age, gender and earlier
      ambulatory surgeries. CONCLUSIONS: As a conclusion, positive results concerning
      patients' knowledge could be achieved with the Internet-based education. The
      Internet is a viable method in ambulatory care.

PMID- 22476363
TI  - Birds flee en mass from New Year's Eve fireworks.
AB  - Anthropogenic disturbances of wildlife, such as noise, human presence, hunting
      activity, and motor vehicles, are becoming an increasing concern in conservation
      biology. Fireworks are an important part of celebrations worldwide, and although
      humans often find fireworks spectacular, fireworks are probably perceived quite
      differently by wild animals. Behavioral responses to fireworks are difficult to
      study at night, and little is known about the negative effects fireworks may have
      on wildlife. Every year, thousands of tons of fireworks are lit by civilians on
      New Year's Eve in the Netherlands. Using an operational weather radar, we
      quantified the reaction of birds to fireworks in 3 consecutive years. Thousands
      of birds took flight shortly after midnight, with high aerial movements lasting
      at least 45 min and peak densities measured at 500 m altitude. The highest
      densities were observed over grasslands and wetlands, including nature
      conservation sites, where thousands of waterfowl rest and feed. The Netherlands
      is the most important winter staging area for several species of waterfowl in
      Europe. We estimate that hundreds of thousands of birds in the Netherlands take
      flight due to fireworks. The spatial and temporal extent of disturbance is
      substantial, and potential consequences are discussed. Weather radar provides a
      unique opportunity to study the reaction of birds to fireworks, which has
      otherwise remained elusive.

PMID- 22476364
TI  - Mental health of Australian Aboriginal women during pregnancy: identifying the
      gaps.
AB  - Despite Australia's high standard of health care provision, Australian Aboriginal
      women continue to experience poor pregnancy outcomes in terms of maternal and
      foetal morbidity and mortality. In an attempt to improve these outcomes, health
      care providers have developed targeted antenatal programmes that aim to address
      identified health behaviours that are known to contribute to poor health during
      pregnancy. While some areas of improvement have been noted in rates of engagement
      with health services, the rates of premature births and low birth weight babies
      continue to be significantly higher than in the non-Aboriginal population. It
      appears that Australian researchers have been focused on the behaviour of the
      individual and have failed to fully consider the impact that social and emotional
      well-being has on both health behaviours and pregnancy outcomes. This review has
      highlighted the need for an approach to both research and clinical practice that
      acknowledges the Aboriginal view of health which encompasses mental, physical,
      cultural and spiritual health. Until clinicians and Aboriginal women have a
      shared understanding of how social and emotional well-being is experienced by
      Aboriginal women, in other words their explanatory model, it is unlikely that any
      meaningful improvements will be seen.

PMID- 22476369
TI  - Examination of prior contest experience and the retention of winner and loser
      effects.
AB  - In many animal taxa, prior contest experience affects future performance such
      that winning increases the chances of winning in the future (winner effect) and
      losing increases the chances of losing in the future (loser effect). It is,
      however, not clear whether this pattern typically arises from experience effects
      on actual or perceived fighting ability (or both). In this study, we looked at
      winner and loser effects in the jumping spider Phidippus clarus. We assigned
      winning or losing experience to spiders and tested them against opponents of
      similar fighting ability in subsequent contests at 1-, 2-, 5-, and 24-h
      intervals. We examined the strength of winner and loser effects, how long effects
      persist, as well as how experience affected perceived and actual fighting
      ability. Our results demonstrate that winner and loser effects are of
      approximately the same magnitude, although loser effects last longer than winner
      effects. Our results also demonstrate that previous experience alters actual
      fighting ability because both the assessment and escalation periods were affected
      by experience. We suggest that the retention time of experience effects depends
      on expected encounter rates as well as other behavioral and ecological factors.
      In systems with short breeding seasons and/or rapidly fluctuating populations,
      context-dependent retention of experience effects may allow males to track their
      status relative to the fluctuating fighting ability of local competitors without
      paying the costs necessary to recall or assess individual competitors.

PMID- 22476370
TI  - Anatomical localization of deep infiltrating endometriosis: 3D MRI
      reconstructions.
AB  - PURPOSE: The goal of this study was to determine the accuracy of three
      dimensional (3D) MRI reconstructions obtained with segmentation technique in the
      preoperative assessment of deep infiltrating endometriosis (DIE) and in
      particular to evaluate rectosigmoid and bladder wall involvement. MATERIALS AND
      METHODS: Institutional review board approval for this study was obtained, and
      each patient gave written informed consent. Fifty-seven consecutive patients with
      diagnosis of DIE who had undergone pelvic MRI at 1.5 T before surgery between
      2007 and 2011, were retrospectively evaluated and 3D post-processed in order to
      obtain a detailed mapping of DIE. A blinded reader interpreted images. MRI
      results were compared with surgical findings and were scored by using a four
      point scale (0_3 score). RESULTS: 36/57 patients with symptomatic DIE underwent
      surgery: 18/36 had endometriotic nodules infiltrating the rectouterine pouch,
      12/36 the vesicouterine pouch, and 6/36 the rectovaginal pouch. The sensitivity
      of MRI and 3D MRI vs. surgery was, respectively, 64% vs. 83%; diagnostic accuracy
      of 3D MRI respect to MRI alone was 86% vs. 67% for localization; 86% vs. 67% for
      dimension; 79% vs. 58% for rectosigmoid infiltration; 92% vs. 75% for bladder
      infiltration. CONCLUSIONS: In this preliminary study, 3D MRI reconstructions
      obtained with semi-automatic method of segmentation provided encouraging results
      for staging DIE preoperatively. In fact, the addition of 3D MRI reconstructions
      improved diagnostic accuracy and staging of DIE providing the exact volume of the
      lesions and enabling a precise mapping of these before surgery.

PMID- 22476371
TI  - Splenic duplication: a rare cause of acute upper gastrointestinal bleeding.
AB  - Acute gastrointestinal bleeding represents a common medical emergency. We report
      the rare case of acute upper gastrointestinal bleeding caused by varices in the
      gastric fundus secondary to splenic duplication. Splenic duplication has been
      only rarely reported in the literature, and no case so far has described the
      associated complication of gastrointestinal bleeding, caused by venous drainage
      of the upper spleen via varices in the gastric fundus. We describe the imaging
      findings from endoscopy, endosonography, computed tomography (CT), flat-panel CT,
      and angiography in this rare condition and illustrate the effective role of intra
      arterial embolization.

PMID- 22476372
TI  - Ovarian mucinous cystadenoma coexisting with benign Brenner tumor: MR imaging
      findings.
AB  - PURPOSE: The purpose of this study was to describe the MR imaging findings of
      ovarian mucinous cystadenomas coexisting with benign Brenner tumors. MATERIALS
      AND METHODS: MR images with a 1.5-T unit obtained in five consecutive patients
      (age range, 51-72 years; mean age, 61 years) with surgically confirmed ovarian
      mucinous cystadenomas coexisting with benign Brenner tumors were retrospectively
      reviewed for the presence, configuration, and signal intensity of cystic and
      solid components of the lesions. RESULTS: Tumors ranged in size from 7.5 to 22.1
      cm (mean, 13.5 cm). In four patients (80%), the size of mucinous cystadenoma
      (range 6.4-22.1 cm; mean, 12.5 cm) was larger than that of Brenner tumor (range
      0.2-9.1 cm; mean, 2.8 cm). All patients (100%) had cystic, and three (60%) had
      solid components. Four patients (80%) showed multilocular cystic, and one (20%)
      showed unilocular cystic appearance. MR imaging findings were classified into
      three patterns: (1) a bulky solid mass adjacent to the cystic component, (2) a
      mural nodule at the periphery of the cystic component, and (3) a cystic component
      without a detectable solid component. All four multilocular cystic areas
      exhibited "stained glass" appearances on both T1- and T2-weighted images, and all
      three solid areas showed homogeneous hypointensity on T2-weighted images.
      CONCLUSION: Mucinous cystadenomas were often larger than the coexisting benign
      Brenner tumors. Mucinous cystadenomas coexisting with benign Brenner tumors
      should be considered when multilocular or unilocular cystic components are
      accompanied by homogeneously hypointense solid components on T2-weighted images.

PMID- 22476373
TI  - Renal vein leiomyosarcoma: imaging and clinical features of a renal cell
      carcinoma mimic.
AB  - Renal vein leiomyosarcoma is a rare tumor whose clinical and imaging features can
      significantly overlap with those of advanced primary renal neoplasms,
      particularly renal cell carcinoma. IRB approval was obtained for a retrospective
      review of clinical and imaging information for five patients with the
      pathologically proven diagnosis of renal vein leiomyosarcoma at two institutions.
      Among the five patients, two were female and three male; average age 58.6 (range
      42-77). Three patients presented with flank or abdominal pain, one with pulmonary
      embolism, and one with weight loss and fatigue. Mass size ranged from 4 to 10 cm.
      Four masses were left-sided and one right-sided. Tumors involved and expanded the
      renal vein in all cases, with tumor extension to the renal hilum in one case,
      through the renal hilum into renal parenchyma in two cases, and into inferior
      vena cava in two cases. All masses demonstrated contrast enhancement, which was
      solely peripheral in one case. In all cases, extrarenal tumor volume was greater
      than renal parenchymal tumor volume. When renal masses are predominantly or
      exclusively intravascular, consideration should be given to the diagnosis of
      renal vein leiomyosarcoma because preoperative biopsy results could significantly
      alter management.

PMID- 22476375
TI  - [Results of nonunion treatment with bone morphogenetic protein 7 (BMP-7)].
AB  - BACKGROUND: Complex patterns of impaired bone healing can result in a severe
      economic and social burden for the patient. Herein we describe the local
      application of recombinant human bone morphogenetic protein 7 (BMP-7). The goal
      of this prospective study is to review the indications, application and
      validation of this therapy. MATERIAL AND METHOD: From June 2002 to June 2008, we
      applied 101 BMP-7 treatments in 101 nonunions of 98 patients. The average age of
      the patients was 50 years (18-88 years). The gender composition was 29 women
      (30%) and 69 men (70%). Before BMP-7 application, patients had already underwent
      surgical treatement an average of 3.3 times (median 3, 1- to 13-times). We used
      BMP-7 "off-label" in all long bones. RESULTS: In 93 cases (92%), we observed
      proper bone healing. The average healing time was 4.8 months (range 1.5-11
      months). The average time from injury to BMP-7 application was 18.4 months (3-84
      months). In 65 cases, BMP-7 application was combined with re-osteosynthesis and
      autologous bone grafting. Serious side effects were not observed. CONCLUSIONS:
      BMP-7 should not be used as general treatment of nonunion in all patients, but
      appears to be effective for the treatment of complex cases. In clinical practice,
      the decision to proceed with off-label use of BMP-7 should be made on a case-by
      case basis.

PMID- 22476376
TI  - [Rupture of the anterior cruciate ligament in growing children: surgical or
      conservative treatment? A systematic review].
AB  - The aim of the study was to examine whether a rupture of the anterior cruciate
      ligament (ACL) in patients with open growth plates should be treated by surgery
      or conservatively. An electronic search was performed in MEDLINE, the Cochrane
      controlled trial register, Embase, and Medpilot. Ten studies including 154
      patients were analyzed regarding conservative treatment and 55 studies including
      935 patients regarding operative treatment. The mean age for the conservative and
      operative treatment groups was 12.3 (10-14.4) years and 13.3 (10-15.8) years,
      respectively. Summing up there were significantly better results concerning
      Lysholm score (95.5 vs 73.2; p<0.05), instability described by the giving way
      phenomenon (2.8 vs 89.5%; p<0.05), and regaining former sports activity level
      (91.2 vs 30.9%; p<0.05) in the operatively treated group. Relative risk for leg
      length differences more than 1 cm or axis deviation more than 3 degrees  after
      surgery was low (2.1%). Reruptures occurred in 3.8% of the cases. The analyzed
      data clearly show that operative treatment is superior to conservative management
      of ACL ruptures in children and adolescents.

PMID- 22476377
TI  - First trimester volumetric measurements: relation with hormone levels and fetal
      heart rate.
AB  - PURPOSE: This study aimed to examine two-dimensional ultrasound (2D US)
      volumetric measurements of 1st trimester structures and their relationship with
      beta-hCG, progesterone, and fetal heart rate (FHR) in 6-10 weeks healthy pregnant
      women. METHODS: Using conventional 2D transvaginal ultrasound imaging, the crown
      rump length (CRL), yolk sac (YS) and gestational sac (GS) were measured in 80
      women. Volumetric measurements were done in 32 cases that were selected among 80
      women, using a simplified formula for the volume of a prolate ellipsoid: V =
      0.523 * length * height * width. The beta-hCG and progesterone levels were
      recorded. The heart rate was determined from M-mode tracings using electronic
      calipers. RESULTS: Moderately positive correlation was found between FHR versus
      CRL, embryo volume and GS volume. FHR increased linearly with CRL value, till CRL
      became 15 mm, after which it formed a plateau. beta-hCG increased linearly till
      CRL was 15 mm, and then it formed a plateau. Progesterone level was stable till
      CRL became 20 mm, embryo volume 2 cm(3), after which it increased linearly.
      CONCLUSION: Various ranges of relations are observed between FHR, obstetric, and
      hormonal measurements. The relationship between these parameters might be used
      for determination of abnormal growth and adverse outcomes in early pregnancy.

PMID- 22476378
TI  - Bone mineral density changes during pregnancy in actively exercising women as
      measured by quantitative ultrasound.
AB  - OBJECTIVE: To evaluate whether bone mineral density (BMD) changes in women
      engaged in active exercises during pregnancy would be different from non
      exercising women. METHODS: Consecutive patients with singleton pregnancies who
      were engaged in active exercise training during pregnancy were prospectively
      recruited over a period of 6 months. Quantitative USG measurements of the os
      calcis BMD were performed at 14-20 weeks and at 36-38 weeks. These patients were
      compared to a control cohort of non-exercising low-risk women. RESULTS: A total
      of 24 physically active women undergoing active physical training of over 10 h
      per week at 20 weeks gestation and beyond (mean 13.1 h, SD 3.3) were compared to
      94 non-exercising low-risk women. A marginal fall in BMD of 0.015 g/cm(2) (SD
      0.034) was demonstrable from early to late gestation in the exercising women,
      which was significantly lower than that of non-exercising women (0.041 g/cm(2);
      SD 0.042; p = 0.005). Logistic regression models confirmed that active exercises
      in pregnancy were significantly associated with the absence of or less BMD loss
      in pregnancy. CONCLUSION: In women actively engaged in physical training during
      pregnancy, the physiological fall in BMD during pregnancy was apparently less
      compared to those who did not regularly exercise.

PMID- 22476379
TI  - Pain levels associated with renal colic and primary dysmenorrhea: a prospective
      controlled study with objective and subjective outcomes.
AB  - OBJECTIVES: To evaluate the degree of pain associated with renal colic and
      primary dysmenorrhea using objective and subjective measurements. METHODS: In
      total, 60 subjects participated in this study. There were 20 subjects in the
      renal colic group (average age 24.45 +/- 2.35 years), 20 subjects in the primary
      dysmenorrhea group (average age 23.75 +/- 1.86 years), and 20 subjects in the
      control group (average age 24.20 +/- 2.57 years). The serum chromogranin A (CgA)
      values were determined by an enzyme-linked immunosorbent assay and the mean pain
      score was assessed by means of a Visual Analog Scale (VAS) for each individual.
      RESULTS: The serum CgA level was 19.83 +/- 19.61 ng/ml for the renal colic group,
      13.45 +/- 8.52 ng/ml for the primary dysmenorrhea group and 12.45 +/- 7.76 ng/ml
      for the control group. The mean VAS score for pain was 7.95 +/- 1.54 for the
      renal colic group and 7.05 +/- 1.50 for the primary dysmenorrhea group.
      CONCLUSIONS: Primary dysmenorrheic pain is as intense as renal colic pain.
      Emergency room physicians should display the same degree of care and attention
      for the treatment of patients with primary dysmenorrhea as they do for patients
      with renal colic, and rapidly initiate an effective treatment for these patients.

PMID- 22476380
TI  - Endometrioma in abdominal scars: case reports of four cases and review of the
      literature.

PMID- 22476381
TI  - Unusual lower genital tract injury caused by bull's horn: prolapse of small
      intestine through vagina-first case report in literature.

PMID- 22476382
TI  - New directions in capacity building: incorporating cultural competence into the
      interactive systems framework.
AB  - The UMBC Psychology Department's Center for Community Collaboration (CCC)
      provides training and support for capacity building to promote substance abuse
      and mental health treatment as well as adherence improvement in community
      agencies funded through the Ryan White Act serving persons living with HIV/AIDS.
      This article describes an approach to dissemination of Evidence Based Practices
      (EBPs) for these services that uses the Interactive Systems Framework (ISF) and
      incorporates a collaborative process involving trainer cultural competence, along
      with a comprehensive assessment of organizational needs, culture, and climate
      that culminates in tailored training and ongoing collaboration. This article
      provides: (1) an overview of the CCC's expanded ISF for the effective
      dissemination of two EBPs-motivational interviewing and the stages of change
      perspective; (2) an examination of the role of trainer cultural competence within
      the ISF framework, particularly attending to organizational culture and climate;
      and (3) case examples to demonstrate this approach for both general and
      innovation-specific capacity building in two community based organizations.

PMID- 22476383
TI  - Silver(I) complexes of 9-anthracenecarboxylic acid and imidazoles: synthesis,
      structure and antimicrobial activity.
AB  - [Ag(2)(9-aca)(2)] (1) (9-acaH = 9-anthracenecarboxylic acid) reacts with a series
      of imidazoles to give [Ag(imidH)(2.3)(CH(3)CN)(0.7)](9-aca) (3),
      [Ag(6)(imidH)(4)(9-aca)(6)(MeOH)(2)] (4), {[Ag(1-Me-imid)(2)](2)[Ag(4)(9
      aca)(6)]} (5), {[Ag(1-Bu-imid)(2)](2)[Ag(4)(9-aca)(6)]} (6) and [Ag(apim)](9
      aca).H(2)O (7) (imidH = imidazole; 1-Me-imid = 1-methylimidazole; 1-Bu-imid = 1
      butylimidazole; apim = 1-(3-aminopropyl)imidazole). The mononuclear complex 3,
      hexanuclear 4-6, and polymeric 7, were all characterised using X-ray
      crystallography. While many of the complexes possess excellent in vitro
      antifungal and antibacterial activities they are, unanimously, more effective
      against fungal cells. The insect, Galleria mellonella, can survive high doses of
      the Ag(i) complexes administered in vivo, and a number of the complexes offer
      significant protection to larvae infected with a lethal dose of pathogenic
      Candida albicans cells.

PMID- 22476384
TI  - Teaching DICOM by problem solving.
AB  - The Digital Imaging and Communications in Medicine (DICOM) is the standard for
      encoding and communicating medical imaging information. It is used in radiology
      as well as in many other imaging domains such as ophthalmology, dentistry, and
      pathology. DICOM information objects are used to encode medical images or
      information about the images. Their usage outside of the imaging department is
      increasing, especially with the sharing of medical images within Electronic
      Health Record systems. However, learning DICOM is long and difficult because it
      defines and uses many specific abstract concepts that relate to each other. In
      this paper, we present an approach, based on problem solving, for teaching DICOM
      as part of a graduate course on healthcare information. The proposed approach
      allows students with diversified background and no software development
      experience to grasp a large breadth of knowledge in a very short time.

PMID- 22476385
TI  - Methods and recommendations for evaluating and reporting a new diagnostic test.
AB  - No standardized guidelines exist for the biostatistical methods appropriate for
      studies evaluating diagnostic tests. Publication recommendations such as the
      STARD statement provide guidance for the analysis of data, but biostatistical
      advice is minimal and application is inconsistent. This article aims to provide a
      self-contained, accessible resource on the biostatistical aspects of study design
      and reporting for investigators. For all dichotomous diagnostic tests, estimates
      of sensitivity and specificity should be reported with confidence intervals.
      Power calculations are strongly recommended to ensure that investigators achieve
      desired levels of precision. In the absence of a gold standard reference test,
      the composite reference standard method is recommended for improving estimates of
      the sensitivity and specificity of the test under evaluation.

PMID- 22476386
TI  - Epidemiology of Acinetobacter spp.-associated healthcare infections and
      colonization among children at a tertiary-care hospital in Saudi Arabia: a 6-year
      retrospective cohort study.
AB  - A retrospective cohort study was conducted among hospitalized children less than
      12 years of age who had Acinetobacter spp. isolated from >=1 cultures between
      October 2001 and December 2007 at King Abdulaziz Medical City in Riyadh, Saudi
      Arabia. Children with multidrug-resistant (MDR) Acinetobacter spp. healthcare
      associated infections (HAIs) were compared to children with antimicrobial
      susceptible Acinetobacter spp. HAIs and to children colonized with Acinetobacter.
      Children with MDR Acinetobacter spp. HAIs were older (p = 0.01), more likely to
      be admitted to an intensive care unit (ICU) (p = 0.06), and had a higher
      mortality rate (p = 0.02) than colonized children. Children with MDR
      Acinetobacter spp. HAIs were older than children with antimicrobial-susceptible
      Acinetobacter spp. HAIs (p = 0.0004), but their mortality rates were similar.
      Among children with MDR Acinetobacter spp. HAIs, burn injuries were the most
      common underlying illness. HAIs caused by MDR or susceptible Acinetobacter spp.
      occurred after prolonged hospitalization, suggesting nosocomial acquisition.
      Patients infected with MDR Acinetobacter spp. frequently received inappropriate
      empiric therapy (73.9 %). Further studies are needed in order to identify
      effective strategies to prevent nosocomial transmission and effective ways of
      improving patient outcomes.

PMID- 22476388
TI  - Linkage disequilibrium between the CYP2C19*17 allele and other clinically
      important CYP2C allelic variants in a healthy Scandinavian population.

PMID- 22476387
TI  - Vorapaxar, an oral PAR-1 receptor antagonist, does not affect the
      pharmacokinetics and pharmacodynamics of warfarin.
AB  - PURPOSE: Vorapaxar is an orally active protease-activated receptor 1 (PAR-1)
      antagonist that inhibits thrombin-induced platelet aggregation. This open-label
      study assessed the pharmacokinetics and pharmacodynamics of single-dose warfarin
      in the presence/absence of multiple-dose vorapaxar in 12 healthy men. METHODS:
      Subjects received two treatments separated by >= 7-day washout: Treatment A
      warfarin 25 mg (Day 1); Treatment B vorapaxar 2.5 mg/day on Days 1-6 and
      vorapaxar 40 mg coadministered with warfarin 25 mg (Day 7). R-warfarin, S
      warfarin, and prothrombin time (PT) were assayed predose and up to 120 h
      postdose. RESULTS: The geometric mean ratio (GMR) as a percentage (warfarin +
      vorapaxar/warfarin) was calculated. The GMR (90 % CIs) estimates of C(max) were
      105 (99, 111) and 105 (99, 112) for R- and S-warfarin, respectively. The GMR (90
      % CIs) estimates of AUC(0-infinity) were 108 (101, 116) and 105 (96, 115) for R-
      and S-warfarin, respectively. The GMR (95 % CIs) estimates of AUC(0-120 h) for PT
      and INR were 97 (95, 98) and 96 (94, 98), respectively. CONCLUSION: Results of
      this study indicate that vorapaxar has no meaningful effect on the
      pharmacokinetics or pharmacodynamics of warfarin, suggesting that the
      coadministration of these two drugs or vorapaxar coadministered with other
      CYP2C9/CYP2C19 substrates is unlikely to cause a clinically significant
      pharmacokinetic drug interaction.

PMID- 22476389
TI  - Association of long-term adherence to evidence-based combination drug therapy
      after acute myocardial infarction with all-cause mortality. A prospective cohort
      study based on claims data.
AB  - PURPOSE: To determine long-term adherence to evidence-based secondary preventive
      combination pharmacotherapy in survivors of acute myocardial infarction (AMI) and
      to investigate the association between adherence to recommended therapy and all
      cause mortality in claims data. METHODS: Prospective cohort study based on claims
      data of an 18.75 % random sample of all persons insured with the local statutory
      health insurance fund AOK Hesse. Study population included patients with hospital
      discharge diagnoses of AMI between 2001 and 2005 excluding those who died within
      the first 30 days after AMI or who had been hospitalised with an AMI in the
      previous 2 years. A total of 3,008 patients were followed up until death,
      cancellation of insurance, or the end of the study period on 31 December 2007,
      whichever came first (median follow-up: 4.2 years). RESULTS: Drug adherence to
      single drug groups as determined by proportion of days covered >=80 % was 21.8 %
      for antiplatelet drugs, 9.4 % for beta-blockers, 45.6 % for ACE inhibitors or
      angiotensin II receptor blockers and 45.1 % for lipid-lowering drugs. A total of
      924 (39.7 %) patients met our definition of guideline adherence: Drugs available
      from three of four relevant drug groups on the same day for at least 50 % of the
      observation time. Of the patients adhering to the guidelines, 17.3 % died and of
      the non-adherents, 32.4 % died. All-cause mortality was 28 % lower for guideline
      adherent patients than for the non-adherent group (adjusted HR 0.72, 95 % CI 0.60
      0.86). CONCLUSIONS: In everyday practice, post AMI patients benefit from
      guideline-oriented treatment, but the percentage of adherent patients should be
      improved.

PMID- 22476391
TI  - Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid
      pharmacokinetics in Chinese epilepsy patients.
AB  - PURPOSE: The aim of this study was to investigate the genetic polymorphisms of
      UGT1A3, UGT1A6, and UGT2B7 in Chinese epilepsy patients and their potential
      influence on the pharmacokinetics of valproic acid (VPA). METHODS: The genetic
      architectures of UGT1A3, UGT1A6, and UGT2B7 in 242 epilepsy patients were
      detected by DNA sequencing and PCR-restriction fragment length polymorphism.
      Steady-state plasma concentrations of VPA in 225 patients who had received VPA
      (approx. 250-1,000 mg/day) for at least 2 weeks were determined and associated
      with UGT polymorphisms. RESULTS: The allelic distribution of UGT1A3 in our
      Chinese epilepsy patients was significantly different from that in healthy
      subjects based on reference data. The standardized trough plasma concentration
      (C(S)) of VPA was much lower in our patients with the UGT1A3*5 variant than in
      the wild type carriers (3.24 +/- 1.05 vs. 4.68 +/- 1.24 MUg.kg.mL(-1).mg(-1), P <
      0.01). UGT polymorphisms had no influence on the pharmacokinetic interactions
      between carbamazepine and VPA. CONCLUSION: Our results suggest that UGT1A3*5 may
      be an important determinant of individual variability in the pharmacokinetics of
      VPA and that it may be necessary to increase VPA dose for UGT1A3*5 carriers to
      ensure its therapeutic range of 50-100 MUg/mL.

PMID- 22476392
TI  - Potential risk factors for medication non-adherence in patients with chronic
      obstructive pulmonary disease (COPD).
AB  - AIMS: To investigate the effect of a range of demographic and psychosocial
      variables on medication adherence in chronic obstructive pulmonary disease (COPD)
      patients managed in a secondary care setting. METHODS: A total of 173 patients
      with a confirmed diagnosis of COPD, recruited from an outpatient clinic in
      Northern Ireland, participated in the study. Data collection was carried out via
      face-to-face interviews and through review of patients' medical charts. Social
      and demographic variables, co-morbidity, self-reported drug adherence (Morisky
      scale), Hospital Anxiety and Depression (HAD) scale, COPD knowledge, Health
      Belief Model (HBM) and self-efficacy scales were determined for each patient.
      RESULTS: Participants were aged 67 +/- 9.7 (mean +/- SD) years, 56 % female and
      took a mean (SD) of 8.2 +/- 3.4 drugs. Low adherence with medications was present
      in 29.5 % of the patients. Demographic variables (gender, age, marital status,
      living arrangements and occupation) were not associated with adherence. A range
      of clinical and psychosocial variables, on the other hand, were found to be
      associated with medication adherence, i.e. beliefs regarding medication
      effectiveness, severity of COPD, smoking status, presence of co-morbid illness,
      depressed mood, self-efficacy, perceived susceptibility and perceived barriers
      within the HBM (p < 0.05). Logistic regression analysis showed that perceived
      ineffectiveness of medication, presence of co-morbid illness, depressed mood and
      perceived barriers were independently associated with medication non-adherence in
      the study (P < 0.05). CONCLUSIONS: Adherence in COPD patients is influenced more
      by patients' perception of their health and medication effectiveness, the
      presence of depressed mood and co-morbid illness than by demographic factors or
      disease severity.

PMID- 22476393
TI  - The clinical utility of a one-shot energy subtraction method for thoracic spine
      radiography.
AB  - BACKGROUND: The interpretation of thoracic spine X-rays is difficult because
      these images cannot clearly visualize the thoracic spine because of the overlap
      with soft tissues, such as the heart and pulmonary blood vessels. Thus, to
      improve the clarity of thoracic spine radiographs using existing radiograph
      equipment, we have investigated a one-shot energy subtraction method to visualize
      thoracic spine radiographs. Our objective was to evaluate whether the thoracic
      spine radiographs generated using this method could visualize the spine more
      clearly than the corresponding original thoracic spine radiographs. METHODS: This
      study included 29 patients who underwent thoracic spine radiographs. We used a
      one-shot energy subtraction method to improve the clarity of thoracic spine
      radiographs. Image definition was evaluated using vertebrae sampled from each
      region of the thoracic spine. Specifically, these were: Th1, Th5, Th9, and Th12.
      Image definition was assessed using a three-point grading system. The
      conventional and processed computed radiographs (both frontal and lateral views)
      of all 29 study patients were evaluated by 5 spine surgeons. RESULTS: In all
      thoracic regions on both frontal and lateral views, the processed images showed
      statistically significantly better clarity than the corresponding conventional
      images, especially at all sampling sites on the frontal view and T5 and 9 on the
      lateral view. CONCLUSIONS: Thoracic spine radiographs generated using this method
      visualized the spine more clearly than the corresponding original thoracic spine
      radiographs. The greatest advantages of this image processing technique were its
      ability to clearly depict the whole thoracic spine on frontal views and the
      middle thoracic spine on lateral views.

PMID- 22476394
TI  - A comparison of tumor prosthesis implantation and pasteurized autograft
      prosthesis composite for proximal tibial tumor.
AB  - BACKGROUND AND OBJECTIVES: Although previous reports on composite biologic
      reconstruction in the proximal tibial location vary, we hypothesized that this
      type of reconstruction may reduce the late infection rate and have advantages in
      terms of longevity by restoring bone stock. METHODS: Primary analysis addressed
      differences between 62 tumor prosthesis (TP) and 25 pasteurized autograft
      prosthesis composite (PPC) reconstructions in terms of survival rates, functional
      outcomes, and temporal patterns of infection. RESULTS: The 10-year survival rates
      of the TP and PPC groups were 73.9 +/- 11.7 and 68.7 +/- 20.1 %, respectively (P
      = 0.64). Reconstructive failure occurred in 16 (25.8 %) in the TP and in 7 (28 %)
      in the PPC group. The cause of failures in the TP group was infection (16),
      whereas those of PPC group were infection (5), loosening (1), and local
      recurrence (1). The mean functional scores of TP (52) and PPC (20) patients that
      maintained a mobile joint were 24.2 (81 %) and 25.1 (83.6 %), respectively.
      Infection rates in the two groups were similar (P = 0.328), but infections
      occurred earlier in the PPC group (P = 0.011). CONCLUSIONS: This comparative
      study suggests composite biological reconstruction shows a comparable long-term
      survival rate to TP reconstruction; however, the composite method has a tendency
      to a lower rate of late infection.

PMID- 22476395
TI  - Drosophila Argonaute-1 is critical for transcriptional cosuppression and
      heterochromatin formation.
AB  - Argonaute-1 (Ago-1) plays a crucial role in gene regulation and genome stability
      via biogenesis of small non-coding RNAs. Two "Argonaute" family genes, piwi and
      Ago-2 in Drosophila are involved in multiple silencing mechanisms in the nucleus,
      transgene cosuppression, long-distant chromosome interaction, nuclear
      organization and heterochromatin formation. To investigate whether Ago-1 also
      plays a similar role, we have generated a series of Ago-1 mutations by excising P
      element, inserted in the Ago-1 promoter (Ago-1k08121). AGO-1 protein is
      distributed uniformly in the nucleus and cytosol in early embryos but accumulated
      predominantly in the cytoplasm during the gastrulation stage. Repeat induced
      silencing produced by the mini-white (mw) array and transcriptional cosuppression
      of non-homologous transgenes Adh-w/w-Adh was disrupted by Ago-1 mutation. These
      effects of Ago-1 are distict from its role in microRNA processing because Dicer
      1, a critical enzyme for miRNA biogenesis, has no role on the above silencing.
      Reduction of AGO-1 protein dislodged the POLYCOMB, EZ (enhancer of zeste) and
      H3me3K27 binding at the cosuppressed Adh-w transgene insertion sites suggesting
      its role in Polycomb dependent cosuppression. An overall reduction of methylated
      histone H3me2K9 and H3me3K27 from the polytene nuclei precisely from the mw
      promoters was also found that leads to concomitant changes in the chromatin
      structure. These results suggest a prominent role of Ago-1 in chromatin
      organization and transgene silencing and demonstrate a critical link between
      transcriptional transgene cosuppression, heterochromatin formation and chromatin
      organization. We propose Drosophila Ago-1 as a multifunctional RNAi component
      that interconnects at least two unrelated events, chromatin organization in the
      nucleus and microRNA processing in the cytoplasm, which may be extended to the
      other systems.

PMID- 22476396
TI  - Size and location of radish chromosome regions carrying the fertility restorer
      Rfk1 gene in spring turnip rape.
AB  - In spring turnip rape (Brassica rapa L. spp. oleifera), the most promising F1
      hybrid system would be the Ogu-INRA CMS/Rf system. A Kosena fertility restorer
      gene Rfk1, homolog of the Ogura restorer gene Rfo, was successfully transferred
      from oilseed rape into turnip rape and that restored the fertility in female
      lines carrying Ogura cms. The trait was, however, unstable in subsequent
      generations. The physical localization of the radish chromosomal region carrying
      the Rfk1 gene was investigated using genomic in situ hybridization (GISH) and
      bacterial artificial chromosome-fluorescence in situ hybridization (BAC-FISH)
      methods. The metaphase chromosomes were hybridized using radish DNA as the
      genomic probe and BAC64 probe, which is linked with Rfo gene. Both probes showed
      a signal in the chromosome spreads of the restorer line 4021-2 Rfk of turnip rape
      but not in the negative control line 4021B. The GISH analyses clearly showed that
      the turnip rape restorer plants were either monosomic (2n=2x=20+1R) or disomic
      (2n=2x=20+2R) addition lines with one or two copies of a single alien chromosome
      region originating from radish. In the BAC-FISH analysis, double dot signals were
      detected in subterminal parts of the radish chromosome arms showing that the
      fertility restorer gene Rfk1 was located in this additional radish chromosome.
      Detected disomic addition lines were found to be unstable for turnip rape hybrid
      production. Using the BAC-FISH analysis, weak signals were sometimes visible in
      two chromosomes of turnip rape and a homologous region of Rfk1 in chromosome 9 of
      the B. rapa A genome was verified with BLAST analysis. In the future, this
      homologous area in A genome could be substituted with radish chromosome area
      carrying the Rfk1 gene.

PMID- 22476397
TI  - Progressive data transmission for anatomical landmark detection in a cloud.
AB  - BACKGROUND: In the concept of cloud-computing-based systems, various authorized
      users have secure access to patient records from a number of care delivery
      organizations from any location. This creates a growing need for remote
      visualization, advanced image processing, state-of-the-art image analysis, and
      computer aided diagnosis. OBJECTIVES: This paper proposes a system of algorithms
      for automatic detection of anatomical landmarks in 3D volumes in the cloud
      computing environment. The system addresses the inherent problem of limited
      bandwidth between a (thin) client, data center, and data analysis server.
      METHODS: The problem of limited bandwidth is solved by a hierarchical sequential
      detection algorithm that obtains data by progressively transmitting only image
      regions required for processing. The client sends a request to detect a set of
      landmarks for region visualization or further analysis. The algorithm running on
      the data analysis server obtains a coarse level image from the data center and
      generates landmark location candidates. The candidates are then used to obtain
      image neighborhood regions at a finer resolution level for further detection.
      This way, the landmark locations are hierarchically and sequentially detected and
      refined. RESULTS: Only image regions surrounding landmark location candidates
      need to be trans- mitted during detection. Furthermore, the image regions are
      lossy compressed with JPEG 2000. Together, these properties amount to at least 30
      times bandwidth reduction while achieving similar accuracy when compared to an
      algorithm using the original data. CONCLUSIONS: The hierarchical sequential
      algorithm with progressive data transmission considerably reduces bandwidth
      requirements in cloud-based detection systems.

PMID- 22476398
TI  - Accrual in supportive care trials in pediatric oncology, a challenge!
AB  - PURPOSE: Treatment protocols in pediatric oncology have historically known high
      accrual rates, up to 94 %. Accrual for supportive care studies on the other hand
      appears to be a challenge. The aim of this study was to search for reasons
      explaining this poor accrual and for possible interventions to improve patient
      enrolment. METHODS: The failure screen log of our supportive care study (the
      Aristocaths study) was analyzed, and subsequently, a literature search was
      performed. RESULTS: The literature search (1985-2011) revealed three factors that
      can influence accrual. Firstly, study implementation and patient enrolment can be
      facilitated by appointing a dedicated clinical investigator in all participating
      centers and by facilitating clinical research nurses. Furthermore, adequate and
      tailor-made information is required for families to make a well-informed decision
      regarding study participation. Lastly, sufficient time should be assured for the
      process of decision making, especially since the number of eligible studies is
      increasing rapidly. Concerning our study, all three elements were met, but the
      most striking finding was the presumed burden of study participation by the
      majority of parents (82 %) as the main argument against randomization.
      CONCLUSIONS: Accrual of pediatric oncology patients in supportive care studies is
      challenging. Nevertheless, well-designed randomized controlled trials in
      supportive care will be essential for the improvement of pediatric cancer care.
      Therefore, we will need to increase awareness through (inter)national supportive
      care working groups regarding the need for supportive care trials and stimulate
      accrual when such trials are open.

PMID- 22476399
TI  - A systematic review of unmet needs of newly diagnosed older cancer patients
      undergoing active cancer treatment.
AB  - PURPOSE: The aim of this study is to systematically review evidence with regard
      to answering the following questions: (1) What are the unmet care needs of older
      persons diagnosed with cancer who are undergoing active cancer treatment? (2)
      What are the predictors of unmet needs of older persons while undergoing active
      cancer treatment? METHODS: A systematic review of the literature published
      between January 1996 and December 2010 was completed. Manuscripts could be
      published in English, French, Dutch, or German searching the Medline, Embase,
      Psychinfo, Cinahl, and the Cochrane Library databases. The literature search was
      performed by two researchers with the assistance of a university librarian.
      Abstracts were reviewed by two reviewers for inclusion. RESULTS: Thirty studies
      were included. A significant proportion of newly-diagnosed patients undergoing
      cancer treatment had unmet needs, ranging from 15 to 93%. The most common needs
      varied by study but included psychological needs, information needs, and needs in
      the physical domain. Most studies showed that the level of unmet needs was
      highest after diagnosis and start of treatment and decreased over time.
      Predictors of unmet needs included: younger age, female gender, depression,
      physical symptoms, marital status, treatment type, income, and education.
      CONCLUSIONS: The level of unmet needs in newly diagnosed older cancer patients
      after the start of treatment is high, and the most common needs are psychological
      and information needs. More research is needed which would focus on the needs of
      older adults with comorbid conditions, and how these comorbid conditions
      influence the level of unmet needs.

PMID- 22476400
TI  - Loss of heterozygosity on chromosome 16q suggests malignancy in core needle
      biopsy specimens of intraductal papillary breast lesions.
AB  - It is often difficult to make a definitive diagnosis of papillary breast lesions
      using core needle biopsy (CNB) specimens. We studied loss of heterozygosity (LOH)
      on chromosome 16q in order to assess its diagnostic use for papillary breast
      lesions in CNB specimens. Of 25 patients with intraductal papillary breast
      tumors, we extracted DNA from paired samples of tumor cells from CNB specimens
      and non-tumor cells from subsequent excision specimens and analyzed LOH at the
      D16S419 and D16S514 loci on chromosome 16q. LOH analysis results were compared
      with final diagnoses based on pathological features of the resected specimens. On
      the CNB specimens, 21 tumors were histologically diagnosed as indeterminate or
      suspicious for malignancy, while four tumors were unambiguously malignant. Of the
      21 indeterminate or suspicious tumors, 11 were finally diagnosed as benign and
      ten as malignant, and on these, LOH analyses were informative for 8 of the 11
      benign tumors and 7 of the 10 malignant tumors. LOH was also informative on two
      of the four tumors unambiguously malignant on CNB. None of the eight informative
      benign tumors showed LOH on 16q. Six of the eleven informative malignant tumors
      showed LOH on 16q. LOH on 16q was significantly different between CNB specimens
      of benign and malignant intraductal papillary tumors (P = 0.007). Analysis of LOH
      on 16q may be helpful in making a definitive diagnosis in cases of papillary
      breast lesions, in both excised and CNB specimens.

PMID- 22476401
TI  - Intraepithelially entrapped blood vessels in oral carcinoma in-situ.
AB  - It can be difficult to make a certain diagnosis in case of an oral borderline
      malignant lesion on hematoxylin-eosin-stained sections only. Furthermore,
      assessment of surgical margins of borderline lesions is difficult with the naked
      eye. We set out to determine the topographical distribution of capillary blood
      vessels within the epithelial zone and to assess its use as an aid for
      histopathological diagnosis and a framework for clinical assessment of lesional
      margins using optical techniques, such as narrow-band imaging (NBI) endoscopy.
      Capillary blood vessels entrapped in the epithelial compartment, which we have
      designated as intraepithelially entrapped blood vessels (IEBVs), were examined
      for their frequency, location, and shape in normal mucosa, dysplasia, and
      carcinoma in-situ (CIS) of the tongue using immunohistochemistry for CD31 and
      type IV collagen. When counted per unit length of epithelial surface, IEBVs
      increased in number significantly in CIS (5.6 +/- 2.8), which was two times more
      than in normal (1.9 +/- 1.6) and dysplastic (2.4 +/- 1.5) epithelia. In addition,
      IEBVs in CIS had compressed shapes with occasional obstruction or collapse with
      hemorrhage and were arranged perpendicular to and extending up to the epithelial
      surface. These characteristic IEBVs in CIS were considered to be generated by
      complex expansion of rete ridges due to carcinoma cell proliferation within the
      limited epithelial space determined by the basement membrane. The recognition of
      IEBVs was helpful in the differential diagnosis of oral CIS, and the present data
      provide a valuable frame of reference for detecting oral CIS areas using such NBI
      based optical devices.

PMID- 22476402
TI  - Nonsebaceous lymphadenoma of salivary glands: proposed development from
      intraparotid lymph nodes and risk of misdiagnosis.
AB  - Nonsebaceous lymphadenoma (NSLA) is a rare benign salivary gland tumor composed
      of lymphoid and epithelial components. By definition, the epithelial component
      lacks sebaceous differentiation and instead displays a wide range of histological
      differentiation. In this study, we have collected nine cases of NSLA to
      characterize their histological and immunohistochemical profiles. The samples
      were histologically reviewed and immunohistochemical stains for CK5/6, CK7, CK14,
      CK18, p63, and Ki67 performed. Patients were six males and three females (mean
      age, 50 years). All tumors were located in the parotid gland and showed intimate
      intermingling of lymphoid tissue with islands or strands of epithelium with a
      wide spectrum of histological differentiation. The immunohistochemical profiles
      mirrored the epithelial differentiation; hence, areas with basaloid or
      lymphoepithelial differentiation strongly expressed CK5/6, CK14, and p63, while
      areas with ductal differentiation showed strong positivity for CK18/CK7 and
      CK5/6/CK14/p63 in luminal and basal cell layers, respectively. A hilus structure
      with salivary inclusions or D2-40 (podoplanin)-positive marginal sinus was
      identifiable in four and nine of the cases, respectively, supporting origin
      within intra-/periparotid lymph nodes. Six cases were initially misdiagnosed as
      other benign (n = 4) or malignant tumors (n = 2). Our study on the second largest
      series of NSLA reported to date provides strong evidence that NSLA belongs to the
      group of salivary gland tumors that pathogenetically develop from embryonic
      salivary gland inclusions in intra-/periparotid lymph nodes. Knowledge of the
      wide histological spectrum of this rare and presumably underreported tumor is
      important in order to avoid misdiagnosis, particularly as malignant tumor.

PMID- 22476403
TI  - HMGA2 protein expression in ovarian serous carcinoma effusions, primary tumors,
      and solid metastases.
AB  - The objective of this study was to analyze the expression and clinical role of
      the high mobility group AT hook (HMGA) protein in advanced-stage serous ovarian
      carcinoma. HMGA2 protein expression was investigated in 199 effusions and in 50
      patient-matched primary tumors and solid metastases using immunohistochemistry.
      Results were analyzed for association with clinicopathologic parameters,
      including chemotherapy response, and survival. HMGA2 was expressed in tumor cells
      in 94.5 %, 96 %, and 90 % of specimens, respectively. There was no difference in
      HMGA2 expression between patient-matched samples from different anatomic sites (p
      > 0.3). HMGA2 expression in chemo-naive samples was significantly higher in older
      patients (p = 0.006, p = 0.01, and p = 0.005 for effusions, primary tumors, and
      solid metastases, respectively). No association was found with residual disease
      volume. Furthermore, HMGA2 expression was not associated with FIGO stage (p >
      0.2), except in chemo-naive effusions (n = 106, p = 0.016). There was no
      difference in HMGA2 expression between chemo-naive samples and samples obtained
      post-chemotherapy in effusions (p = 0.2) or primary tumors (p = 0.1). However,
      solid metastases obtained after chemotherapy exposure had higher HMGA2 expression
      compared with chemo-naive samples (p = 0.032). HMGA2 expression was unrelated to
      chemotherapy response or survival. However, it was directly related to protein
      expression of the previously studied cancer stem cell marker Nestin (p = 0.01)
      and the gap junction protein claudin-7 (p = 0.02) and inversely related to the
      mRNA level of the E-cadherin repressor SIP1 (p = 0.02). This study provides
      evidence that HMGA2 is universally expressed in advanced-stage ovarian serous
      carcinoma irrespective of anatomic site, suggesting that HMGA2 may have a
      clinical role as therapeutic target.

PMID- 22476404
TI  - The Effect of Question Framing and Response Options on the Relationship between
      Racial Attitudes and Beliefs about Genes as Causes of Behavior.
AB  - Prior research suggests that the attribution of individual and group differences
      to genetic causes is correlated with prejudiced attitudes toward minority groups.
      Our study suggests that these findings may be due to the wording of the questions
      and to the choice of response options. Using a series of vignettes in an online
      survey, we find a relationship between racial attitudes and genetic attributions
      when respondents are asked to make causal attributions of differences between
      racial groups. However, when they are asked to make causal attributions for
      characteristics shown by individuals, no such relationship is found. The response
      scale used appears to make less, if any, difference in the results. These
      findings indicate that the way questions about genetic causation of behavior are
      framed makes a significant contribution to the answers obtained because it
      significantly changes the meaning of the questions. We argue that such framing
      needs to be carefully attended to, not only in posing research questions but also
      in discourse about genetics more generally.

PMID- 22476405
TI  - The Polls-Review: Inaccurate Age and Sex Data in the Census Pums Files: Evidence
      and Implications.
AB  - We discover and document errors in public-use microdata samples ("PUMS files") of
      the 2000 Census, the 2003-2006 American Community Survey, and the 2004-2009
      Current Population Survey. For women and men age 65 and older, age- and sex
      specific population estimates generated from the PUMS files differ by as much as
      15 percent from counts in published data tables. Moreover, an analysis of labor
      force participation and marriage rates suggests the PUMS samples are not
      representative of the population at individual ages for those age 65 and over.
      PUMS files substantially underestimate labor-force participation of those near
      retirement age and overestimate labor-force participation rates of those at older
      ages. These problems were an unintentional byproduct of the misapplication of a
      newer generation of disclosure-avoidance procedures carried out on the data. The
      resulting errors in the public-use data could significantly impact studies of
      people age 65 and older, particularly analyses of variables that are expected to
      change by age.

PMID- 22476406
TI  - The oral cone of Anomalocaris is not a classic ''peytoia''.
AB  - The Cambro-Ordovician anomalocaridids are large ecdysozoans commonly regarded as
      ancestors of the arthropods and apex predators. Predation is indicated partly by
      the presence of an unusual "peytoia"-type oral cone, which is a tetraradial outer
      ring of 32 plates, four of which are enlarged and in perpendicular arrangement.
      This oral cone morphology was considered a highly consistent and defining
      characteristic of well-known Burgess Shale taxa. It is here shown that
      Anomalocaris has a different oral cone, with only three large plates and a
      variable number of smaller and medium plates. Its functional morphology suggests
      that suction, rather than biting, was used for food ingestion, and that
      anomalocaridids in general employed a range of different scavenging and predatory
      feeding strategies. Removing anomalocaridids from the position of highly
      specialized trilobite predators forces a reconsideration of the ecological
      structure of the earliest marine animal communities in the Cambrian.

PMID- 22476407
TI  - Annexin-V promotes anti-tumor immunity and inhibits neuroblastoma growth in vivo.
AB  - The goal of the current study is to determine the effects of blocking
      phosphatidylserine (PS) on the growth of neuroblastoma in mice. PS, an anionic
      phospholipid restricted to the cytoplasmic surface of plasma membranes in most
      cells, is externalized to the surface of apoptotic cells. PS has been shown to
      induce immune tolerance to self-antigens. PS can also be found on the surface of
      live cells and in particular tumor cells. Annexin-V (AnV) is a protein that
      specifically binds and blocks PS. To determine the effects of blocking PS with
      AnV on tumor growth and immunogenicity, mice were inoculated with AGN2a, a poorly
      immunogenic murine neuroblastoma that expresses high level of PS on the cell
      surface. Survival and anti-tumor T cell response were determined. AGN2a were
      engineered to secrete AnV. Secreted protein effectively blocked tumor PS. 40 % of
      mice inoculated with AnV-expressing AGN2a cells survived free of tumor, whereas
      none of the mice inoculated with control cells survived (p = 0.0062). The
      benefits of AnV were lost when mice were depleted of T cells. The findings
      suggest that AnV could protect mice from tumor challenge through an immune
      mediated mechanism. Mice were then immunized with irradiated AnV-secreting or
      control cells, and challenged with wild-type AGN2a cells. AnV-secreting cell
      vaccine protected 80 % of mice from AGN2a challenge, while control cell vaccine
      prevented tumor growth in only 30 % of animals (p = 0.012). ELISPOT analysis
      demonstrated that AnV-secreting cell vaccine induced a greater frequency of
      interferon-gamma producing splenic T cells. T cells isolated from mice immunized
      with AnV-secreting but not control vaccine lysed AGN2a. In summary, AnV blocked
      PS, enhanced T cell mediated tumor immunity, and inhibited tumor growth.

PMID- 22476408
TI  - Pre-clinical assessment of autologous DC-based therapy in ovarian cancer patients
      with progressive disease.
AB  - Dendritic cell-based vaccines offer promise for therapy of ovarian cancer.
      Previous studies have demonstrated that oxidation of several antigens, including
      ovarian cancer cells, using hypochlorous acid strongly enhances their
      immunogenicity and their uptake and presentation by dendritic cells. The response
      of T cells and dendritic cells to autologous tumour from patients with active
      disease has not previously been investigated. Monocyte-derived dendritic cells
      were generated from patients with active disease and activated by co-culture with
      oxidised tumour cells and the TLR agonist poly I:C. The dendritic cells showed an
      activated phenotype, but secreted high levels of TGFbeta. Co-culture of the
      antigen-loaded dendritic cells with autologous T cells generated a population of
      effector T cells that showed a low level of specific lytic activity against
      autologous tumour, as compared to autologous mesothelium. The addition of
      neutralising antibody to TGFbeta in DC/T cell co-cultures increased the levels of
      subsequent tumour killing in three samples tested. Co-culture of monocytes from
      healthy volunteers with the ovarian cell line SKOV-3 prior to differentiation
      into dendritic cells reduced the ability of dendritic cells to stimulate
      cytotoxic effector cells. The study suggests that co-culture of dendritic cells
      with oxidised tumour cells can generate effector cells able to kill autologous
      tumour, but that the high tumour burden in patients with active disease may
      compromise dendritic cell and/or T cell function.

PMID- 22476409
TI  - Transnasal endoscopic resection of a nasopharyngeal pleomorphic adenoma: a rare
      case report.
AB  - Pleomorphic adenoma (PA) is the most common benign tumor of the major and minor
      salivary glands, but rarely found in the nasopharynx. A PA originating from the
      left lateral wall of the nasopharynx was found in a 52-year-old female who
      presented with nasal obstruction, left-side otalgia, aural fullness, tinnitus and
      subjective hearing loss. It was successfully removed by transnasal endoscopic
      surgery (TES) and navigator system assessed our location, due to the proximity of
      critical anatomic structures such as the left internal carotid. We believe that
      the TES for primary and recurrent nasopharyngeal benign tumors is feasible and
      safe in properly selected patients, due to superior functional and cosmetic
      results and a low complication rate. Tumor characteristics and location should be
      taken into account when selecting cases for the right procedure for this lesions;
      transnasal endoscopic surgery is safe and preferable, carrying less potential
      morbidity compared to open procedures.

PMID- 22476410
TI  - Cochlear implant fixation: are sutures really necessary?
AB  - The objective of this study was to evaluate retrospectively the risk of cochlear
      implant migration and complications related to the here presented alternative
      surgical fixation technique of the receiver/stimulator without any foreign body
      materials. Fixation of the implant was achieved by an "L-shaped" muscle
      periosteal flap and an exactly shaped bony well. Between January 2006 and
      December 2009, 247 consecutive primary cochlear implantations have been performed
      with the described technique in the Department of Otorhinolaryngology, Head and
      Neck surgery of the University of Cologne (tertiary referral center). Devices
      from different manufacturers have been implanted. Implantation age ranged from 6
      months to 78 years (mean age: 24.50 years). Follow-up time ranged from 12 to 60
      months. Neither implant dislocations nor migrations were observed in our
      patients. In four very young children (1.6 %), additional suture fixation of the
      implant was performed. Postoperative complications, i.e. seroma or hematoma were
      observed in a total of six cases (2.4 %). The here presented surgical fixation
      technique is a sufficient and reliable way for fixation of cochlear implants
      independent of the device type.

PMID- 22476411
TI  - Combined-modality treatment improved outcome in sinonasal undifferentiated
      carcinoma: single-institutional experience of 21 patients and review of the
      literature.
AB  - The optimal treatment of sinonasal undifferentiated carcinoma (SNUC) remains
      unclear. We report our results on the outcome and toxicity of patients with SNUC
      treated by a combined modality and attempt to define the optimal treatment
      strategies by reviewing the literature. Between 1996 and 2010, 21 consecutive
      patients with SNUC were treated by any combination of surgery, chemotherapy and
      radiotherapy. End points were local control (LC), regional control (RC), disease
      free (DFS), cause-specific (CSS) overall survival (OS), and late toxicity. Organ
      preservation was defined as visual preservation without orbital exenteration.
      After median follow-up of 54 months, the 5-year actuarial rates of LC, RC, DFS,
      CSS, and OS were 80, 90, 64, 74, and 74 % respectively. On multivariate analysis,
      T-stage and multimodality treatment approach correlated significantly with LC.
      Elective nodal irradiation was given to 42 % of high-risk node-negative patients.
      None of them developed regional failure. The overall 5-year incidence of grade >=
      2 late toxicity was 30 %. Treatment-related blindness was significantly decreased
      in patients treated with intensity-modulated radiotherapy (IMRT), compared to 2D
      and 3D-conformal radiotherapy (3DCRT), with organ preservation rates of 86 and 14
      % respectively (p = 0.006). We concluded that combined-modality treatment with
      three, or at least two, modalities resulted in good LC, but with high overall
      rate of late toxicity. However, the incidence of late toxicity and permanent
      visual impairment were decreased over time by the introduction of IMRT. Because
      of the improvement in therapeutic ratio achieved by using IMRT, this highly
      conformal radiation technique should be the standard of care in patients with
      SNUC.

PMID- 22476412
TI  - Winogradskyella multivorans sp. nov., a polysaccharide-degrading bacterium
      isolated from seawater of an oyster farm.
AB  - A novel bacterial strain, designated T-Y1(T), capable of degrading a variety of
      polysaccharides was isolated from seawater of an oyster farm in the South Sea,
      Korea. It was found to be aerobic, Gram-negative, non-flagellated, non-gliding
      and rod-shaped. Strain T-Y1(T) grew optimally at 25  degrees C, at pH 7.0-7.5 and
      in the presence of 2 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on
      16S rRNA gene sequences showed that strain T-Y1(T) belonged to the genus
      Winogradskyella. Strain T-Y1(T) exhibited 16S rRNA gene sequence similarity
      values of 95.0-96.8 % to the type strains of recognized Winogradskyella species
      and less than 94.5 % to other validly named species. The chemotaxonomic data
      concurred with the phylogenetic inference. Strain T-Y1(T) contained MK-6 as the
      predominant menaquinone and anteiso-C(15:0), iso-C(15:0), iso-C(15:1) G and iso
      C(16:0) 3-OH as the major fatty acids. The major polar lipids of strain T-Y1(T)
      were phosphatidylethanolamine and two unidentified lipids. The DNA G+C content
      was 36.2 mol%. Differential phenotypic properties, together with its phylogenetic
      distinctiveness, enabled strain T-Y1(T) to be differentiated from the recognized
      Winogradskyella species. On the basis of the data presented here, strain T-Y1(T)
      is considered to represent a novel species of the genus Winogradskyella, for
      which the name Winogradskyella multivorans sp. nov. is proposed. The type strain
      is T-Y1(T) (=KCTC 23891(T) = CCUG 62216(T)).

PMID- 22476413
TI  - Evaluation of the binding of oxovanadium(IV) to human serum albumin.
AB  - The understanding of the biotransformations of insulin mimetic vanadium complexes
      in human blood and its transport to target cells is an essential issue in the
      development of more effective drugs. We present the study of the interaction of
      oxovanadium(iv) with human serum albumin (HSA) by electron paramagnetic resonance
      (EPR), circular dichroism (CD) and visible absorption spectroscopy. Metal
      competition studies were done using Cu(II) and Zn(II) as metal probes. The
      results show that V(IV)O occupies two types of binding sites in albumin, which
      compete not only with each other, but also with hydrolysis of the metal ion. In
      one of the sites the resulting V(IV)O-HSA complex has a weak visible CD signal
      and its X-band EPR spectrum may be easily measured. This was assigned to amino
      acid side chains of the ATCUN site. The other binding site shows stronger signals
      in the CD in the visible range, but has a hardly measurable EPR signal; it is
      assigned to the multi metal binding site (MBS) of HSA. Studies with fatted and
      defatted albumin show the complexity of the system since conformational changes,
      induced by the binding of fatty acids, decrease the ability of V(IV)O to bind
      albumin. The possibility and importance of ternary complex formation between
      V(IV)O, HSA and several drug candidates - maltol (mal), picolinic acid (pic), 2
      hydroxypyridine-N-oxide (hpno) and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone (dhp)
      was also evaluated. In the presence of maltol the CD and EPR spectra
      significantly change, indicating the formation of ternary VO-HSA-maltol
      complexes. Modeling studies with amino acids and peptides were used to propose
      binding modes. Based on quantitative RT EPR measurements and CD data, it was
      concluded that in the systems with mal, pic, hpno, and dhp (V(IV)OL(2))(n)(HSA)
      species form, where the maximum value for n is at least 6 (mal, pic). The degree
      of formation of the ternary species, corresponding to the reaction V(IV)OL(2) +
      HSA -->/<-- V(IV)OL(2)(HSA) is hpno > pic >= mal > dhp. (V(IV)OL)(n)(HSA) type
      complexes are detected exclusively with pic. Based on the spectroscopic studies
      we propose that in the (V(IV)OL(2))(n)(HSA) species the protein bounds to
      vanadium through the histidine side chains.

PMID- 22476414
TI  - [Natural and artificial knee joints as a focus of orthopedic and casualty
      surgical research].

PMID- 22476415
TI  - [Musculoskeletal modeling of the patellofemoral joint. Dynamic analysis of
      patellar tracking].
AB  - Numerical simulations contribute to the understanding of patellofemoral diseases.
      Whereas cadaveric studies are limited with respect to reproducibility of results,
      the impact of different operative approaches can be systematically evaluated
      based on mathematical models. The objective of this study was to introduce a
      musculoskeletal model which is capable of describing the dynamic interactions
      within the patellofemoral joint. It contains major bony and soft tissue
      structures of the right leg including the medial patellofemoral ligament (MPFL).
      Two operative approaches were considered based on the model to illustrate the
      effect on patellofemoral biomechanics during active knee flexion: On the one hand
      the effect of femoral insertion during MPFL reconstruction on medial soft tissue
      tension, and on the other hand the difference in patella kinematics before and
      after total knee arthroplasty. Finally, the potential of musculoskeletal models
      is discussed.

PMID- 22476416
TI  - [The oncofetal gene survivin - a possible target gene for regenerative therapy
      concepts in cartilaginous tissue].
AB  - Survivin, the smallest member of the inhibitor of the apoptosis protein gene
      family (IAP) is a key molecule for mammalian cell cycle regulation and cellular
      survival. Of note these functions have been thought to be limited to embryonic
      and malignant tissues. However, a growing body of evidence indicates a limited
      expression of survivin in some highly specific adult tissues and cells. In the
      present study it has been demonstrated that the antiapoptotic protein survivin is
      re-expressed in osteoarthritic human cartilage and primary human chondrocytes.
      Furthermore, the data indicated that survivin significantly affects cell cycle
      regulation and cellular survival. The modulation of survivin expression and
      function in cartilaginous tissues might be important for understanding
      osteoarthritis and the development of regenerative strategies.

PMID- 22476417
TI  - [Reconstruction of osteochondral defects with a collagen I hydrogel. Results of a
      prospective multicenter study].
AB  - STUDY GOALS: The aim of the study was to evaluate the therapeutic benefit of
      CaReS(r), a type I collagen hydrogel-based autologous chondrocyte implantation
      technique, for the treatment of osteochondral defects of the knee (Outerbridge
      grades III and IV) within a prospective multicenter study. MATERIAL AND METHODS:
      A total of 116 patients in 9 clinical centers were treated with CaReS between
      2003 and 2008. The Cartilage Injury Evaluation Package 2000 of the International
      Cartilage Repair Society (ICRS) was employed for data acquisition and included
      the subjective International Knee Documentation Committee score (IKDC score), the
      pain level (visual analog scale, VAS), the physical and mental SF-36 score, the
      overall treatment satisfaction and the functional IKDC status of the indexed
      knee. Follow-up evaluation was performed 3, 6 and 12 months after surgery and
      annually thereafter. RESULTS: The mean defect size treated was 5.4 +/- 2.7 cm(2)
      with 30% of the cartilage defects being  <=4 cm(2) and 70%  >=4 cm(2). The mean
      follow-up period was 30.2 +/- 17.4 months (minimum 12 months and maximum 60
      months). The mean IKDC score significantly improved from 42.4 +/- 13.8
      preoperatively to 70.5 +/- 18.7 (p < 0.01) in the mean follow-up period. Global
      pain level significantly decreased (p < 0.001) from 6.7 +/- 2.2 preoperatively to
      3.2 +/- 3.1 at the latest follow-up. Both the physical and mental components of
      the SF-36 score significantly increased. At the latest follow-up 80% of the
      patients rated the overall treatment satisfaction as either good or very good.
      The functional IKDC knee status clearly improved from preoperative to the latest
      follow-up when 23.4% of the patients reported having no restriction of knee
      function (I), 56.3% had mild restriction (II), 17,2% had moderate restriction
      (III) and 3.1% revealed severe restriction (IV). CONCLUSIONS: The CaReS technique
      is a clinically effective and safe method for the reconstruction of isolated
      osteochondral defects of the knee joint and reveals promising clinical outcome up
      to 5 years after surgery. A longer follow-up period and larger patient cohorts
      are needed to evaluate the sustainability of CaReS treatment.

PMID- 22476418
TI  - [Bone tissue engineering. Reconstruction of critical sized segmental bone defects
      in the ovine tibia].
AB  - Well-established therapies for bone defects are restricted to bone grafts which
      face significant disadvantages (limited availability, donor site morbidity,
      insufficient integration). Therefore, the objective was to develop an alternative
      approach investigating the regenerative potential of medical grade
      polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk
      HA) scaffolds.Critical sized ovine tibial defects were created and stabilized.
      Defects were left untreated, reconstructed with autologous bone grafts (ABG) and
      mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray
      analysis, torsion testing and quantitative computed tomography (CT) analyses were
      performed. Radiological analysis confirmed the critical nature of the defects.
      Full defect bridging occurred in the autograft and partial bridging in the mPCL
      TCP group. Only little bone formation was observed with silk-HA scaffolds.
      Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and
      CT analysis a significantly higher amount of bone formation for the ABG group
      when compared to the silk-HA group. No significant difference was determined
      between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL
      TCP scaffolds combined can serve as an alternative to autologous bone grafting in
      long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells
      or growth factors represents an attractive means to further enhance bone
      formation.

PMID- 22476419
TI  - [Anterior meniscotibial ligaments. Forces under various load conditions].
AB  - The main biomechanical function of the knee meniscus is to enlarge the contact
      area of the tibiofemoral joint leading to a reduction in articular cartilage
      contact stress. The meniscal attachments are essential for converting the axial
      load into circumferential tension in the meniscal periphery. Consequently,
      meniscal substitutes need sufficient anchorage to the tibial plateau to
      adequately restore the biomechanical function of a replaced meniscus. Therefore
      the aim of the present study was to investigate the loads acting on the anterior
      meniscotibial attachments under various joint loads.

PMID- 22476420
TI  - [Does increased tibial slope reduce the wear rate of unicompartmental knee
      prostheses? An in vitro investigation].
AB  - INTRODUCTION: Unicompartmental knee arthroplasty (UKA) has become a standard
      procedure with good clinical outcome in patients with isolated medial
      osteoarthritis of the knee. However, the survival rates of UKA are still inferior
      compared to that of total knee arthroplasty. Aseptic loosening and wear are
      responsible for more than 50% of revisions. Therefore, this study evaluated the
      influence of the tibial slope on the wear rate in a medial UKA. MATERIALS AND
      METHODS: The wear rate of a medial mobile-bearing UKA (Univation(r) Aesculap,
      Tuttlingen, Deutschland) was evaluated according to the ISO 14243-1:2002(E) norm
      with a customized four-station servo-hydraulic knee wear simulator (EndoLab,
      Thansau, Germany). In the first group, the prostheses was medially implanted with
      0 degrees  slope (n = 3) and in the second group the prostheses was medially
      implanted with 8 degrees  slope (n = 3). The lateral side was kept constant with
      0 degrees  in both groups. For each implant, a total of 5.0 million cycles was
      performed and after every 0.5 million cycles the gravimetric wear rate was
      determined. RESULTS: The wear rate in the 0 degrees  slope group was 3.46 +/-
      0.59 mg/million cycles and therefore significantly higher than in the 8 degrees 
      slope group with 0.99 +/- 0.42 mg/million cycles (p < 0.01). DISCUSSION: An
      increase in the tibial slope leads to a reduced wear rate in a mobile-bearing
      UKA. Therefore, at least for this mobile-bearing UKA a higher tibial slope seems
      favorable to reduce the wear. However, before an optimal position of the tibial
      slope can be recommended, further investigations are required to evaluate the
      influence of the tibial slope on other factors, such as the ligament tension or
      the strain on the lateral compartment.

PMID- 22476422
TI  - [Conservative treatment methods. Definition, epidemiology and socio-economic
      importance of non-specific low back pain].

PMID- 22476421
TI  - [Comorbidity from the patient perspective - does it work? Validity of a
      questionnaire on self-estimation of comorbidity (SCQ-D)].
AB  - To minimize the medical effort for the measurement of comorbidity, which is a
      relevant factor for various outcome measures, the Self-Administered Comorbidity
      Questionnaire (SCQ) for patient self-evaluation has been developed. After
      successfully testing the psychometric characteristics and content of the original
      English version a validation of the German translation (SCQ-D) has so far been
      lacking. A total of 218 patients with gonarthrosis and coxarthrosis (average age
      71.5 years) were included in the survey. A questionnaire for doctors as well as
      patients was used to collect data at five different measurement times
      (postoperative, beginning and end of rehabilitation as well as 4 months and 1
      year postoperatively). To evaluate the matching of comorbidities according to the
      SCQ-D and the Charlson Comorbidity Index (CCI), aggregate indices for "problems"
      and "treatment" as well as correlation and kappa coefficients were calculated.
      The assessment of predictive validity in terms of treatment outcome was
      operationalized using the WOMAC and the postoperative 1 year hospitalization by
      applying multilevel models. The patient self-assessment using the SCQ-D
      correlated well with the physician assessment using CCI in terms of aggregate
      indices of 13 given disease groups with r = 0.49 (problems) and r = 0.48
      (treatment). However, the results showed significant differences for certain
      diseases in the conclusions. The comorbidity measured by the SCQ-D proved to be a
      valid predictor of the hospitalization and the treatment outcome. Concerning the
      need for resource efficient data collection especially in large sample studies,
      the SCQ-D is a useful patient self-administered instrument to assess the type and
      extent of comorbidities.

PMID- 22476423
TI  - [Hindfoot valgus. Diagnosis and therapy of flatfoot].
AB  - The clinical finding of flatfoot is characterized by a flattening of the medial
      longitudinal arch and valgus deformity of the hindfoot. The differential
      diagnosis of flatfoot is the physiological, flexible, contracted flatfoot, which
      occurs as a congenital or acquired deformity. Congenital flatfoot deformity
      requires early intensive therapy, while a flexible flatfoot in children has a
      good prognosis and conservative treatment usually leads to a stable and
      sufficient load-bearing foot. Severe flatfoot in children can be corrected
      successfully by simple, minimally invasive procedures. In adults with symptomatic
      flatfoot, which usually occurs due to an insufficiency of the tendon of the
      tibialis posterior, conservative therapy with insoles, shoe modifications and
      physiotherapeutic measures can lead to significant improvement, otherwise
      surgical correction is recommended. Early, stage-appropriate therapy helps to
      prevent an impending decompensation of the hindfoot.

PMID- 22476424
TI  - Surgical site infection and malignant soft tissue tumors.

PMID- 22476426
TI  - Polysaccharide hemostatic system reduces blood loss in high-body-mass-index
      patients undergoing simultaneous bilateral total knee arthroplasty.
AB  - BACKGROUND: To investigate the efficacy of a topically applied hemostatic agent
      used to reduce blood loss in patients undergoing simultaneous bilateral total
      knee arthroplasty (TKA). METHODS: Thirty-two patients (5 male, 27 female) mean
      age 65 +/- 9.3 (46-80) undergoing single-stage bilateral TKA were enrolled in the
      study and divided in two groups. Groups 1 and 2 consisted of patients with body
      mass index (BMI) <30 and >30, respectively. Polysaccharide hemostatic agent (PHA;
      3 g) was applied topically to the right knees of each patient intraoperatively.
      The left knees were used as controls. A negative suction drain was used and the
      effect of PHA and BMI on postoperative bleeding was evaluated. RESULTS: Blood
      loss was significantly higher (p = 0.027, r = 0.397) for patients with higher
      BMI. Treatment by local application of PHA to potential bleeding sites
      significantly reduced blood loss-314 +/- 151 ml (50-600) for the right knees
      versus 468 +/- 140 ml (150-700) for the left knees (p = 0.007) in group 1; 420 +/
      251 ml (100-900) for the right knees versus 620 +/- 229 ml (350-1125) for the
      left knees (p = 0.036) in group 2. Blood loss reduction between the right and
      left knees was no different between the two groups (p = 0.173). CONCLUSIONS: By
      reducing blood loss and the need for postoperative blood transfusion in patients
      with high BMI, PHA can be of value as adjuvant therapy in new blood-management
      procedures in major joint-replacement surgery.

PMID- 22476427
TI  - Periosteal microvascular reorganization after tibial reaming and intramedullary
      nailing in rats.
AB  - BACKGROUND: Intramedullary reaming and nailing of long bones impairs the
      endosteal circulation, often causing necrosis of the inner region of the bone
      cortex. We hypothesized that compensatory hypertrophy of the periosteal
      microcirculation may develop in response to mechanical destruction of the
      endosteum, and that this may affect bone survival in these circumstances. In
      these studies, nailing was performed with materials that affect regeneration of
      the endosteum differently, and the effects on the tibial periosteal
      microvasculatory organization were examined. METHODS: In male Wistar rats, the
      right tibia was reamed and implanted with an inert titanium nail or a less
      osseointegrative polyethylene nail; the contralateral tibial endosteum was
      destroyed by reaming. Reaming without nailing or sham operation was performed on
      both extremities in two other groups of rats. Twelve weeks later, the
      anteromedial and anterolateral surfaces of the tibias were exposed by a
      microsurgical technique. The structural characteristics of the periosteal
      microcirculation (vessel density and distribution of vessel diameters) were
      determined by intravital videomicroscopy and computer-assisted analysis. The
      stability of the implants was assessed on the basis of grades 0-2 on a
      qualitative scale. RESULTS: Tibial reaming alone caused significant increases in
      overall blood vessel and capillary densities in the periosteum compared with
      those of the intact tibias. Implantation with a titanium nail resulted in firm
      embedding of the nail and caused changes in the periosteal vasculature similar to
      those after reaming alone. In contrast, implantation of a polyethylene nail was
      followed by the development of marked instability of the endomedullary implant
      and significant increases in the percentage of capillaries and the vessel density
      in the periosteum. CONCLUSIONS: Destruction of the endosteal microcirculation per
      se brings about an increase in periosteal vascular density, which is further
      augmented if implantation is performed with a material which delays regeneration
      of the endosteal circulation.

PMID- 22476428
TI  - Comparison of the intramedullary nail and low-profile plate for unstable
      metacarpal neck fractures.
AB  - BACKGROUND: There is no robust evidence for the best treatment practice for
      metacarpal neck fractures. The purpose of this comparative study was to
      investigate whether the intramedullary nail or low-profile plate allows for good
      clinical and radiological results for displaced metacarpal neck fractures.
      METHODS: We prospectively reviewed 30 patients with a displaced metacarpal neck
      fracture who underwent surgery: 15 with intramedullary nails and 15 with low
      profile plates. Radiographic and clinical outcomes of both groups were compared.
      Objective findings of range of finger motion and grip strength were assessed at
      3, 6, and 12 months postoperatively. RESULTS: There was no non-union, and
      postoperative complications included extensor tendon rupture in one and transient
      ulnar nerve neuritis in two. Radiological parameters after the fracture healing
      were comparable between the two groups. Postoperative range of finger motion was
      better in patients with the intramedullary nail, and acquired grip strength in
      the low-profile plate group was superior to that in the intramedullary nail
      group. CONCLUSIONS: The current results indicate that both procedures are highly
      effective in maintaining fracture restorations. Plate fixation provides earlier
      recovery of powerful hand function, and intramedullary nailing allows a wide
      range of finger motion.

PMID- 22476429
TI  - Mutation screening of RAD51C in high-risk breast and ovarian cancer families.
AB  - Deleterious mutations in the RAD51C gene, which encodes a DNA double-strand break
      repair protein, have been reported to confer high-penetrance susceptibility to
      both breast and ovarian cancer. To confirm this we conducted a mutation screen of
      the RAD51C gene in 192 probands from high-risk breast and/or ovarian cancer
      families that do not carry BRCA1 or BRCA2 mutations. The nine exons of the RAD51C
      gene containing protein coding sequence were screened for mutations in genomic
      DNA from family probands by high-resolution melting analysis and direct DNA
      sequencing. Four missense variants, p.Ser364Gly, p.Ala126Thr, p.Val169Ala, and
      p.Thr287Ala were detected in six patients. The p.Ser364Gly variant is a novel
      variant predicted to have little influence on RAD51C activity. The p.Ala126Thr
      and p.Val169Ala variants have been reported to have no association with risk of
      breast cancer in a case-control study. However, p.Thr287Ala disrupts the DNA
      repair activity of RAD51C, suggesting some influence on risk. Consistent with
      published results from similar follow-up studies, we suggest that RAD51C
      mutations are rare events among high-risk breast cancer and breast/ovarian cancer
      families. Large population-based studies will be needed to reliably assess the
      prevalence and penetrance of inactivating mutations in the RAD51C susceptibility
      gene.

PMID- 22476430
TI  - Uroepithelial and kidney carcinoma in Lynch syndrome.
AB  - Increased risk for urological tumors has been observed in mutation carriers with
      Lynch syndrome (LS). In this study, we evaluated the clinical features of
      uroepithelial (bladder and ureter) and kidney cancers in 974 Finnish mutation
      carriers. Altogether 30 patients had a total of 34 urological tumors: 12 ureter,
      12 bladder, and 10 kidney cancers. Urological tumor was the only tumor in 9 (30
      %) patients, and metachronous other tumor occurred in 21 (70 %). The occurrence
      of uroepithelial cancers was significantly higher in MSH2 mutation carriers (6 %;
      95 % CI, 2.7-11.0) than in MLH1 carriers (2 %; 95 % CI, 1.1-3.2) and MSH6
      mutation carriers (0 %) (p = 0.014). The mean ages of patients at the time of
      diagnosis were: bladder cancer, 57 years; ureter cancer, 58 years; and kidney
      cancer, 64 years. Overall 5-year survival rates were 70 % (95 % CI, 0.32-0.89) in
      bladder cancer, 81 % (95 % CI, 0.45-0.95) in ureter cancer, and 75 % (95 % CI,
      0.31-0.93) in kidney cancer. Cancer-specific 5-year survival rates were 70 % (95
      % CI, 0.32-0.89) in bladder cancer, 91 % (95 % CI, 0.51-0.98) in ureter cancer,
      and 100 % in kidney cancer. In conclusion, early age of onset was observed in
      patients with uroepithelial tumors, but not in patients with kidney cancer. The
      frequency of uroepithelial tumors was significantly higher in MSH2 mutation
      carriers than in MLH1 carriers. Further studies with larger numbers of patients,
      however, are needed to evaluate the potential benefit of surveillance of
      urological tumors in LS.

PMID- 22476432
TI  - Roles of histone H3K9 methyltransferases during Drosophila spermatogenesis.
AB  - Epigenetic regulation of gene expression by covalent modification of histones is
      important for germ line cell development. In mammals, histone H3 lysine 9 (H3K9)
      specific histone methyltransferases (HMTases), such as G9a, SETDB1, and SUV39H,
      play critical roles, but the contribution of H3K9-specific HMTases in Drosophila
      remains to be clarified, especially in male sperm. Here, we performed
      immunocytochemical analyses with a specific antibody to dG9a, Drosophila G9a
      ortholog, and demonstrated localization in the cytoplasm from the growth to
      elongation stages of spermatogenesis. In the subsequent early canoe stage, strong
      dG9a signals were detected exclusively in nuclei, suggesting a regulatory role.
      However, mono-, di-, and trimethylated H3K9 signals were not extensively
      decreased in a homozygous dG9a null mutant throughout these stages. In contrast,
      mono- and trimethylated H3K9 signals were extensively decreased in a heterozygous
      DmSetdb1 mutant during spermatogenesis, and similar reduction in monomethylated
      H3K9 signals was observed in a homozygous Su(var)3-9 mutant. Therefore, DmSETDB1
      is likely to be mainly responsible for mono- and trimethylation of H3K9 and
      SU(VAR)3-9 for monomethylation of H3K9 during spermatogenesis. However, the
      reduced methylation of H3K9 in premeiotic spermatocytes did not influence X-Y
      chromosome disjunction in male meiosis, suggesting that it may not be critical
      for spermatogenesis in Drosophila.

PMID- 22476433
TI  - Feeding decisions of eastern bluebirds are situationally influenced by fledgling
      plumage color.
AB  - The relative amount of resources that avian parents provide to individual
      offspring within a brood represents a strategy that can have large effects on
      reproductive success. We tested whether parental feeding decisions of eastern
      bluebirds Sialia sialis are influenced by offspring plumage color by presenting
      pairs of differently colored fledglings side by side and observing how they were
      provisioned by parents. After a control period, we manipulated blue plumage color
      so that one sibling in each trial became relatively dark and one became
      relatively bright. During neither the control nor the experimental periods did
      either parent consistently feed naturally brighter or experimentally brightened
      sons more than drab sons. Under specific circumstances, however, both parents
      directed a higher proportion of their feeding attempts to more brightly colored
      sons. Paternal feeding attempts to brighter offspring during both the control and
      experimental periods increased in relation to the brightness of these fledglings
      relative to their brothers. Maternal feeding decision, on the other hand, were
      influenced by numerous variables during control and experimental periods
      including the date of the trial, the difference in mass between fledglings, the
      feeding behavior of fathers during the trial, the relative investment by fathers
      during the nestling stage, and the amount of UV chroma in fledgling plumage.
      Taken together, these results suggest that equal provisioning of offspring is the
      strategy most commonly adopted by eastern bluebirds but more brightly colored
      offspring will be fed preferentially when resources for offspring are limited.

PMID- 22476434
TI  - Subchronic hepatotoxicity evaluation of 1,2,4-tribromobenzene in Sprague-Dawley
      rats.
AB  - Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage
      for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There
      were no TBB exposure-related clinical signs of toxicity or changes in body
      weight. Liver weight increases were dose and exposure time related and
      statistically significant at >=10 mg/kg per d. Incidence and severity of
      centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and
      time related. The 75 mg/kg per d group had minimally increased mitoses within
      hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was
      considered TBB exposure related at >=25 mg/kg per d. Concentrations of blood TBB
      increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 ug/mL (2.5-75
      mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for
      13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg
      per d was selected based on the statistically significant incidence of hepatocyte
      hypertrophy at doses >=10 mg/kg per d.

PMID- 22476436
TI  - Correlation between platelet-derived microparticle enumeration by flow cytometry
      and phospholipid-dependent procoagulant activity in microparticles: the
      centrifugation step matters!

PMID- 22476435
TI  - Linear and nonlinear analysis of heart rate variability in coronary disease.
AB  - OBJECTIVE: Coronary artery disease (CAD) and acute myocardial infarction (AMI)
      are associated with a reduction of heart rate variability (HRV). The aim of this
      study was to compare the HRV of CAD patients with and without AMI (CAD-AMI) with
      health-matched controls by linear (spectral analysis) and nonlinear [Shannon
      entropy (SE), conditional entropy (CE) and symbolic analysis (SA)] analysis.
      METHODS: Fifty-eight men were divided into three groups: healthy (n = 19, 57 +/-
      4 years), CAD (n = 20, 56 +/- 10 years) and CAD-AMI (n = 19, 54 +/- 12 years).
      The RR intervals were recorded at rest in the supine position for 10 min with an
      HR monitor (Polar((r))S810i). A series of 250 beats was selected to analyze
      variance, spectral analysis, SE, CE [complexity index (CI), normalized CI (NCI)]
      and SA (0V, 1V, 2LV and 2ULV patterns), as well as 0V (no significant variation)
      and 2ULV (two significant unlike variations), which reflect sympathetic and vagal
      modulation, respectively. One-way ANOVA (or the Kruskal-Wallis test when
      appropriate) and Pearson correlation were used. RESULTS: The CAD group had higher
      body mass index and weight than the CAD-AMI group, but no differences were found
      between the healthy and AMI groups. There were no differences between the groups
      regarding linear and nonlinear analysis. The 0V and 2ULV patterns were
      significantly correlated with the SE, CI and NCI of the three groups.
      INTERPRETATION: There was no difference between the groups regarding cardiac
      autonomic modulation by linear and nonlinear methods, which may be due to beta
      blocker use, coronary angioplasty and the exercise capacity of healthy subjects.

PMID- 22476437
TI  - Sex-specific DNA methylation and gene expression in andromonoecious poplar.
AB  - The andromonoecious poplar is an exceptional model system for studying sex
      specific flower development in dioecious plants. There is increasing evidence
      that epigenetic regulation, particularly DNA methylation, is an important
      regulatory factor during flower development. Here, methylation-sensitive
      amplified polymorphism (MSAP) was used to screen for sex-specific DNA methylation
      alterations in the andromonoecious poplar. The sequences of 27 sex-specific
      amplified fragments were obtained from DNA prepared from sex-specific flower
      tissues. PtGT2, PtPAL3, and PtCER4, which are homologous to MF26, MF29, and MF35,
      respectively, were cloned as candidate genes. Expression analysis and DNA
      methylation pattern profiling of the three candidate genes revealed that gene
      expression upregulation was always associated with gene body methylation. The
      results suggested that DNA methylation sites have the potential to regulate the
      genes' transcript levels. These three genes were shown to play important roles
      during different phases of flower development. This study will help to provide
      candidates for future experiments aimed at understanding the mechanism, whereby
      DNA methylation regulates gene expression in poplar. KEY MESSAGES: We report the
      first screen for sex-specific DNA methylation alterations in the andromonoecious
      poplar. 27 sex-specific methylation sites were identified. The gene expression
      levels and DNA methylation patterns were detected for three candidate genes.

PMID- 22476438
TI  - Transcriptome analysis of the roots at early and late seedling stages using
      Illumina paired-end sequencing and development of EST-SSR markers in radish.
AB  - The tuberous root of radish is an important vegetable, but insufficient
      transcriptomic and genomic data are currently available to understand the
      molecular mechanisms underlying tuberous root formation and development. High
      throughput transcriptomic sequencing is essential to generate a large transcript
      sequence data set for gene discovery and molecular marker development. In this
      study, a total of 107.3 million clean reads were generated using Illumina paired
      end sequencing technology. De novo assembly generated 61,554 unigenes with an
      average length of 820 bp. Based on a sequence similarity search with known
      proteins or nucleotides, 85.51 % (52,634), 90.18 % (55,507) and 54 % (33,242)
      consensus sequences showed homology with sequences in the Nr, Nt and Swiss-Prot
      databases, respectively. Of these annotated unigenes, 21,109 and 17,343 unigenes
      were assigned to gene ontology categories and clusters of orthologous groups,
      respectively. A total of 27,809 unigenes were assigned to 123 pathways in the
      Kyoto Encyclopedia of Genes and Genomes database. Analysis of transcript
      differences between libraries from the early and late seedling developmental
      stages demonstrated that starch and sucrose metabolism and phenylpropanoid
      biosynthesis may be the dominant metabolic events during tuberous root formation
      and plant hormones probably play critical roles in regulation of this
      developmental process. In total, 14,641 potential EST-SSRs were identified among
      the unigenes, and 12,733 primer pairs for 2,511 SSR were obtained. Summarily,
      this study gave us a clue to understand the radish tuberous root formation and
      development, and also provided us with a valuable sequence resource for novel
      gene discovery and marker-assisted selective breeding in radish. KEY MESSAGE: De
      novo assembled and characterized the radish tuberous root transcriptome; explored
      the mechanism of radish tuberous root formation; development of EST-SSR markers
      in radish.

PMID- 22476440
TI  - Pediatric palliative care-when quality of life becomes the main focus of
      treatment.
AB  - Pediatric palliative care (PPC) focuses on children and adolescents with life
      limiting diseases. It may be initiated at various points of the disease
      trajectory, if possible early enough to support living with the best possible
      quality of life despite a limited lifespan. From birth to adolescence, children
      with a broad spectrum of diseases may benefit from PPC. Since 50% of deaths in
      childhood occur within the first year of life, PPC is just as relevant to
      neonatology. Causes of death in the neonate and young infant are due to perinatal
      conditions such as preterm birth and congenital disorders and syndromes; in older
      children, external causes, such as traumatic injuries, outweigh disease-related
      causes of death. PPC may last from a few hours or days for neonates to many years
      for children with complex chronic conditions. For neonates, PPC often has the
      character of end-of-life (EOL) care followed by bereavement care for the family.
      For older children, PPC can clearly be differentiated from EOL care; its
      indications include progress or deterioration of disease, marked instability of
      the child's condition, increase in the need for technical or medical support,
      increase in suffering, or failure of treatment. If a child's need for palliative
      care is established, useless and potentially harmful treatments may be withheld
      and informed choices can be made about treatment, care, and the remaining life of
      the child. Conclusion This review aims to provide knowledge for clinicians who
      care for children and adolescents at risk of dying from their disease. PPC can
      improve the child's remaining lifetime by focusing on quality of life and goals
      that are defined by the child and his or her family.

PMID- 22476439
TI  - An evaluation on the neuropsychological tests used in the assessment of
      postchemotherapy cognitive changes in breast cancer survivors.
AB  - OBJECTIVES: The choice of appropriate neuropsychological tests is important in
      evaluating the onset, severity, duration, and site of cognitive changes in
      postchemotherapy breast cancer survivors. This literature review is designed to
      evaluate and provide a summary of suitable neuropsychological tests to determine
      cognitive changes in breast cancer survivors. METHOD: A literature search
      restricted to publications in English before June 2011 was performed using the
      following combination of keywords: "neuropsychological assessments," "breast
      cancer," "chemotherapy," and "cognitive impairment." Only observational studies
      that performed cognitive assessments on breast cancer survivors were included.
      The neuropsychological assessments were grouped as "objective" (traditional
      batteries and screening tests), "subjective," or "computerized." RESULTS: Of the
      43 studies extracted, memory (88 %) and attention/concentration (88 %) are the
      two most commonly assessed domains. A majority (63 %) employed the use of
      Wechsler Adult Intelligent Scale (an objective test), while only 49 %
      incorporated subjective assessments to assess perceived cognitive impairment.
      Computerized tests received low popularity (28 %) despite their numerous
      advantages, which include overcoming the language- and cultural-dependent
      limitations of traditional objective tests. CONCLUSIONS: In the selection of a
      suitable neuropsychological tool to determine the onset, severity, site, and
      duration of cognitive changes in breast cancer survivors, incorporation of both
      subjective and objective tests is essential to facilitate a comprehensive
      assessment. With more validation work performed in future studies, it may be
      feasible to employ computerized neuropsychological assessments in both clinical
      and research settings.

PMID- 22476441
TI  - [The experience of being admitted to a psychiatric clinic: part 1: development of
      a questionnaire (QAE-P)].
AB  - BACKGROUND: The aim of the present study was to develop a questionnaire to assess
      the perception and evaluation of admission to a psychiatric hospital from a
      patient's perspective (QAE-P). MATERIAL AND METHODS: Based on existing literature
      and a preparatory pilot study, a questionnaire consisting of 126 items was
      developed, and 708 inpatients based in 6 psychiatry and psychotherapy clinics
      were asked to answer the items. The resulting data were split into two data sets.
      In the first subset, exploratory factor analysis was used to help determine the
      number of scales and provide the basis for item reduction. The resulting
      questionnaire was validated by means of confirmatory factor analyses (CFA) in the
      second data subset. RESULTS: The resulting questionnaire comprises 33 items in 7
      scales, which assess: (1) helpful, positive relations with staff members; (2)
      offering of medical explanations to patients and their involvement in treatment
      planning; (3) evaluation of rooms and clinical environment; (4) dissatisfaction
      with doctors and staff members; (5) evaluation of handling of ward rules by
      staff; (6) perception of ward atmosphere; and (7) negative perception of other
      inpatients. The plausibility of this factorial structure was supported by the
      results of the CFA. CONCLUSIONS: The QAE-P is a short and feasible questionnaire
      that meets the criteria of classic test theory and assesses different dimensions
      of the patient's experience of admission to a psychiatric hospital.

PMID- 22476442
TI  - [Early dementia as primary syndrome of schizophrenia].

PMID- 22476444
TI  - Expression and regulation of macrophage migration inhibitory factor (MIF) in
      feeding American dog ticks, Dermacentor variabilis.
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine
      produced by many mammalian tissues. It is also found in ticks and may function to
      aid the tick in regulating host responses to tick feeding. Our hypothesis is that
      MIF functions in tick blood meal acquisition and pathogen transmission. This
      study was performed to understand the expression and regulation of MIF in the
      American dog tick, Dermacentor variabilis during early stages of blood feeding.
      We used quantitative reverse transcriptase PCR to study the gene expression
      during the first 96 h of feeding. Increases in MIF gene expression were observed
      in salivary gland and midgut tissues during the first 6 days of feeding. RNAi
      mediated gene knockdown of D. variabilis MIF was demonstrated but we did not
      observe measureable phenotypic impact on blood meal acquisition in female ticks.
      These observations are consistent with previously published data on the lone star
      tick Amblyomma americanum and suggest that MIF may not have a direct impact on
      tick blood meal acquisition. Silencing of subolesin, a putative transcription
      factor, down-regulated MIF expression by 50 %.

PMID- 22476443
TI  - Interphase chromatin organisation in Arabidopsis nuclei: constraints versus
      randomness.
AB  - The spatial chromatin organisation and molecular interactions within and between
      chromatin domains and chromosome territories (CTs) are essential for fundamental
      processes such as replication, transcription and DNA repair via homologous
      recombination. To analyse the distribution and interaction of whole CTs,
      centromeres, (sub)telomeres and ~100-kb interstitial chromatin segments in
      endopolyploid nuclei, specific FISH probes from Arabidopsis thaliana were applied
      to 2-64C differentiated leaf nuclei. Whereas CTs occupy a distinct and defined
      volume of the nucleus and do not obviously intermingle with each other in 2-64C
      nuclei, ~100-kb sister chromatin segments within these CTs become more non
      cohesive with increasing endopolyploidy. Centromeres, preferentially located at
      the nuclear periphery, may show ring- or half-moon like shapes in 2C and 4C
      nuclei. Sister centromeres tend to associate up to the 8C level. From 16C nuclei
      on, they become progressively separated. The higher the polyploidy level gets,
      the more separate chromatids are present. Due to sister chromatid separation in
      highly endopolyploid nuclei, the centromeric histone variant CENH3, the 180-bp
      centromeric repeats and pericentromeric heterochromatin form distinct subdomains
      at adjacent but not intermingling positions. The (sub)telomeres are frequently
      associated with each other and with the nucleolus and less often with
      centromeres. The extent of chromatid separation and of chromatin decondensation
      at subtelomeric chromatin segments varies between chromosome arms. A mainly
      random distribution and similar shapes of CTs even at higher ploidy levels
      indicate that in general no substantial CT reorganisation occurs during
      endopolyploidisation. Non-cohesive sister chromatid regions at chromosome arms
      and at the (peri)centromere are accompanied by a less dense chromatin
      conformation in highly endopolyploid nuclei. We discuss the possible function of
      this conformation in comparison to transcriptionally active regions at insect
      polytene chromosomes.

PMID- 22476445
TI  - Testing prey DNA fingerprinting on Amblyseius largoensis (Acari: Phytoseiidae)
      predation of Raoiella indica (Acari: Tenuipalpidae).
AB  - Molecular detection of predation by identifying prey markers in the digestive
      tract of predators has developed into a powerful tool to assess predator-prey
      systems in which diet identification is too time consuming or impossible. Here we
      explore its utility for detecting predation of the pest mite Raoiella indica
      Hirst by the predatory mite Amblyseius largoensis Muma, taking advantage of the
      color the predator acquires after eating this mite to cross-reference our
      results. For this, a ~410 bp segment of the cytochrome c oxidase subunit I (COI)
      mitochondrial gene marker specific for the subfamily Tetranychoidea was used.
      Amblyseius largoensis that had recently eaten were collected from greenhouse
      colonies containing both mites, and isolated from any other food source. Predator
      mites were taken for fingerprinting at 24, 48, 72 and 96 h of starving after
      collection, and the same process was repeated a second time, offering pollen as
      an alternative food source to see whether detection changed. Lastly, a sampling
      trial was conducted in the greenhouse, in which mites were collected regardless
      of their color and frozen immediately for fingerprinting. Raoiella indica DNA was
      detected for 48 h on starving predators, and for 96 h on those who had eaten
      pollen. The segment was detected in 26 % of the samples collected on the trial.
      This technique needs refinement specific for this system, but the results
      obtained here confirm that it could turn into a very useful tool for assessing
      aspects of this predator-prey system.

PMID- 22476446
TI  - Does patient volume affect clinical outcomes in adult intensive care units?
AB  - PURPOSE: This systematic review assessed if outcomes in adult intensive care
      units (ICUs) are related to hospital and ICU patient volume. METHODS: A
      systematic search strategy was used to identify studies reporting on volume
      outcome relationship in adult ICU patients till November 2010. Inclusion of
      articles was established through a predetermined protocol. Two reviewers assessed
      studies independently and data extraction was performed using standardized data
      extraction forms. RESULTS: A total of 254 articles were screened. Of these 25
      were relevant to this study. After further evaluation a total of 13 studies
      including 596,259 patients across 1,068 ICUs met the inclusion criteria and were
      reviewed. All were observational cohort studies. Four of the studies included all
      admissions to ICU, five included mechanically ventilated patients, two reported
      on patients admitted with sepsis and one study each reported on patients admitted
      with medical diagnoses and post cardiac arrest patients admitted to ICU,
      respectively. There was a wide variability in the quantitative definition of
      volume and classification of hospitals and ICUs on this basis. Methodological
      heterogeneity amongst the studies precluded a formal meta-analysis. A trend
      towards favourable outcomes for high volume centres was observed in all studies.
      Risk-adjusted mortality rates revealed a survival advantage for a specific group
      of patients in high volume centres in ten studies but no significant difference
      in outcomes was evident in three studies. CONCLUSIONS: The results indicate that
      outcomes of certain subsets of ICU patients--especially those on mechanical
      ventilation, high-risk patients, and patients with severe sepsis--are better in
      high volume centres within the constraints of risk adjustments.

PMID- 22476447
TI  - Thirty years of home mechanical ventilation in children: escalating need for
      pediatric intensive care beds.
AB  - PURPOSE: To describe trends in pediatric home mechanical ventilation (HMV) and
      their impact on the use of pediatric intensive care unit (PICU) beds. METHODS:
      Review of all children who had started HMV in a single center for HMV. RESULTS:
      Between 1979 and 2009, HMV was started in 197 patients [100 (51%) with invasive
      and 97 with noninvasive ventilation], with a median age of 14.7 (range 0.5-17.9)
      years. Most patients (77%) were males with a neuromuscular disorder (66%). The
      number of children receiving HMV increased from 8 in the 1979-1988 period to 122
      in the 1999-2008 period. This increase occurred foremost in patients aged 0-5
      years and was accompanied by a sharp rise in the use of PICU beds. In 150
      patients (76%), HMV was initiated on an ICU with a total of 12,440 admission
      days, of which 10,385 days (83%) could be attributed to 67 patients who started
      non-electively with invasive HMV. Of the latter, 52 patients had been admitted to
      a PICU with a total of 9,335 admission days. At the end of the study, 134
      patients (68%) were still being ventilated, 43 patients (22%) had died, 11
      patients (6%) were weaned from HMV, 4 patients (2%) did not want to continue HMV
      and 5 patients (3%) were lost to follow-up. CONCLUSIONS: Over time, there was an
      impressive increase in the application of HMV in children. This increase was most
      obvious in the youngest age group with invasive HMV, and these children had very
      long stays in the PICU.

PMID- 22476448
TI  - Diaphragm ultrasonography to estimate the work of breathing during non-invasive
      ventilation.
AB  - PURPOSE: Ultrasonography allows the direct observation of the diaphragm. Its
      thickness variation measured in the zone of apposition has been previously used
      to diagnose diaphragm paralysis. We assessed the feasibility and accuracy of this
      method to assess diaphragmatic function and its contribution to respiratory
      workload in critically ill patients under non-invasive ventilation. METHODS: This
      was a preliminary physiological study in the intensive care unit of a university
      hospital. Twelve patients requiring planned non-invasive ventilation after
      extubation were studied while spontaneously breathing and during non-invasive
      ventilation at three levels of pressure support (5, 10 and 15 cmH(2)O). Diaphragm
      thickness was measured in the zone of apposition during tidal ventilation and the
      thickening fraction (TF) was calculated as (thickness at inspiration - thickness
      at expiration)/thickness at expiration. Diaphragmatic pressure-time product per
      breath (PTP(di)) was measured from oesophageal and gastric pressure recordings.
      RESULTS: PTP(di) and TF both decreased as the level of pressure support
      increased. A significant correlation was found between PTP(di) and TF (rho =
      0.74, p < 0.001). The overall reproducibility of TF assessment was good but the
      coefficient of repeatability reached 18% for inter-observer reproducibility.
      CONCLUSIONS: Ultrasonographic assessment of the diaphragm TF is a non-invasive
      method that may prove useful in evaluating diaphragmatic function and its
      contribution to respiratory workload in intensive care unit patients.

PMID- 22476449
TI  - Classification of sepsis, severe sepsis and septic shock: the impact of minor
      variations in data capture and definition of SIRS criteria.
AB  - PURPOSE: To quantify the effects of minor variations in the definition and
      measurement of systemic inflammatory response syndrome (SIRS) criteria and organ
      failure on the observed incidences of sepsis, severe sepsis and septic shock.
      METHODS: We conducted a prospective, observational study in a tertiary intensive
      care unit in The Netherlands between January 2009 and October 2010. A total of
      1,072 consecutive adults were included. We determined the upper and lower limits
      of the measured incidence of sepsis by evaluating the influence of the use of an
      automated versus a manual method of data collection, and variations in the number
      of SIRS criteria, concurrency of SIRS criteria, and duration of abnormal values
      required to make a particular diagnosis. RESULTS: The measured incidence of SIRS
      varied from 49% (most restrictive setting) to 99% (most liberal setting).
      Subsequently, the incidences of sepsis, severe sepsis and septic shock ranged
      from 22 to 31%, from 6 to 27% and from 4 to 9% for the most restrictive versus
      the most liberal measurement settings, respectively. In non-infected patients, 39
      98% of patients had SIRS, whereas still 17-6% of patients without SIRS had an
      infection. CONCLUSIONS: The apparent incidence of sepsis heavily depends on minor
      variations in the definition of SIRS and mode of data recording. As a
      consequence, the current consensus criteria do not ensure uniform recruitment of
      patients into sepsis trials.

PMID- 22476450
TI  - Prevalence of dental erosion in adolescent competitive swimmers exposed to gas
      chlorinated swimming pool water.
AB  - OBJECTIVES: The purpose of this study was to analyze the prevalence of dental
      erosion among competitive swimmers of the local swimming club in Szczecin,
      Poland, who train in closely monitored gas-chlorinated swimming pool water.
      MATERIALS AND METHODS: The population for this survey consisted of a group of
      junior competitive swimmers who had been training for an average of 7 years, a
      group of senior competitive swimmers who had been training for an average of 10
      years, and a group of recreational swimmers. All subjects underwent a clinical
      dental examination and responded to a questionnaire regarding aspects of dental
      erosion. In pool water samples, the concentration of calcium, magnesium,
      phosphate, sodium, and potassium ions and pH were determined. The degree of
      hydroxyapatite saturation was also calculated. RESULTS: Dental erosion was found
      in more than 26 % of the competitive swimmers and 10 % of the recreational
      swimmers. The lesions in competitive swimmers were on both the labial and palatal
      surfaces of the anterior teeth, whereas erosions in recreational swimmers
      developed exclusively on the palatal surfaces. Although the pH of the pool water
      was neutral, it was undersaturated with respect to hydroxyapatite. CONCLUSION:
      The factors that increase the risk of dental erosion include the duration of
      swimming and the amount of training. An increased risk of erosion may be related
      to undersaturation of pool water with hydroxyapatite components. CLINICAL
      RELEVANCE: To decrease the risk of erosion in competitive swimmers, the degree of
      dental hydroxyapatite saturation should be a controlled parameter in pool water.

PMID- 22476451
TI  - The accuracy of digital templating: a comparison of short-stem total hip
      arthroplasty and conventional total hip arthroplasty.
AB  - PURPOSE: Selection of the correct femoral stem size is crucial in total hip
      arthroplasty for an uncomplicated implantation and good initial stability. Pre
      operative templating has been shown to be a valuable tool in predicting the
      correct implant size. For short-stem total hip arthroplasty (SHA), which recently
      is increasingly used, it is unknown if templating can be performed as reliable as
      conventional total hip arthroplasty (THA). METHODS: A total of 100 hip
      arthroplasties, 50 with SHA and 50 with THA, were templated by four orthopaedic
      surgeons each. The surgeons had different levels of professional experience and
      performed a digital template of the acetabular and femoral component on the pre
      operative radiographs. The results were compared with the truly inserted implant
      size. RESULTS: For the femoral stems the average percentage of agreement (+/- 1
      size) was 89.0 % in SHA and 88.5 % in THA. There was no significant difference
      among surgeons in the accuracy of templating the correct stem size and no
      significant difference between templating SHA and THA. For the acetabular
      component the average percentage of agreement (+/- 1 size) was 75.8 %. However,
      the more experienced surgeons showed a significant higher accuracy for templating
      the correct cup size than the less experienced surgeons. CONCLUSION: Digital
      templating of SHA can predict the stem sizes as accurately as conventional THA.
      Therefore digital templating is also recommendable for SHA, as it helps to
      predict the implant size prior to surgery and thereby might help to avoid
      complications.

PMID- 22476452
TI  - Polyethylene terephthalate (PET) enhances chondrogenic differentiation of ovine
      meniscocytes in a hyaluronic acid/polycaprolactone scaffold in vitro.
AB  - PURPOSE: The purpose of this study was to assess the effect of polyethylene
      terephthalate (PET) on proliferation, differentiation, and attachment of ovine
      meniscocytes seeded in a hyaluronic acid/polycaprolactone biomaterial (BF-1)
      METHODS: BF-1 (30 % hyaluronic acid and 70 % polycaprolactone) cylinders with PET
      (CO-PET) or without PET, were seeded with 2 x 10(6) ovine meniscus cells. The
      specimens were harvested in triplets at 12 hours, seven, 14, 21 and 28 days. DNA
      content was measured to test proliferation, histological analysis for cell
      morphology, and biochemical assessment of glycosaminoglycan content and RT-PCR
      for type I and II collagen were used to assess differentiation, with
      immunohistochemistry as post-translational control. Attachment was evaluated by
      electronic microscopy at 28 days. RESULTS: DNA content was consistent and equal
      across groups, suggesting no effect of PET on cell proliferation. However, the BF
      1 CO-PET showed a higher percentage of cells with spherical morphology which is
      typical for a chondrocytic phenotype. This biomaterial with PET also showed a
      higher type II collagen mRNA expression and an eightfold higher GAG-content than
      the material without PET. Small amounts of type I collagen mRNA expression were
      present on both materials at all time points. PCR results were confirmed by
      immunohistochemistry. CONCLUSION: Addition of PET to a hyaluronic
      acid/polycaprolactone biomaterial enhances a cartilaginous phenotype, increased
      type II collagen mRNA expression and a higher GAG production in ovine
      mensicocytes.

PMID- 22476453
TI  - Advanced buckyball joints: synthesis, complex formation and computational
      simulations of centrohexaindane-extended tribenzotriquinacene receptors for C60
      fullerene.
AB  - The synthesis of a structurally optimized tribenzotriquinacene receptor 9 is
      described, which is extended by centrohexaindane moieties to give rise to a half
      round concave ball bearing, with optimum shape complementarity towards C(60)
      fullerene. Spectroscopic investigations reveal that this novel host forms a 1 : 1
      host-guest complex with C(60) with a complex stability constant of K(1) = 14,550
      +/- 867 M(-1), which is considerably higher than those reported for structurally
      related tribenzotriquinacene hosts reported previously. Both the suppression for
      binding of a second receptor (i.e. formation of a 2 : 1 host-guest complex) as
      well as the increase of complex stability of the 1 : 1 complex can be
      rationalized in terms of multiple additive van der Waals and pi-pi interactions
      between C(60) and the aromatic groups of the receptor, as revealed by DFT + D and
      force-field calculations. Combining results from spectroscopic and theoretical
      investigations leads to predictions in light of future receptor designs, which-
      apart from shape complementarity--will have to consider an optimized electronic
      match (i.e. partial charge transfer) between the receptor and the fullerene host.

PMID- 22476454
TI  - Rapid endocytosis is triggered upon imbibition in Arabidopsis seeds.
AB  - During seed imbibition and embryo activation, rapid change from a metabolically
      resting state to the activation of diverse extracellular and/or membrane bound
      molecules is essential and, hence, endocytosis could be activated too. In fact,
      we have documented endocytic internalization of the membrane impermeable
      endocytic tracer FM4-64 already upon 30 min of imbibition of Arabidopsis seeds.
      This finding suggest that endocytosis is activated early during seed imbibition
      in Arabidopsis. Immunolocalization of rhamnogalacturonan-II (RG-II) complexed
      with boron showed that whereas this pectin is localized only in the cell walls of
      dry seed embryos, it starts to be intracellular once the imbibition started.
      Brefeldin A (BFA) exposure resulted in recruitment of the intracellular RG-II
      pectin complexes into the endocytic BFA-induced compartments, confirming the
      endocytic origin of the RG-II signal detected intracellularly. Finally,
      germination was significantly delayed when Arabidopsis seeds were germinated in
      the presence of inhibitors of endocytic pathways, suggesting that trafficking of
      extracellular molecules might play an important role in the overcome of
      germination. This work constitutes the first demonstration of endocytic processes
      during germination and opens new perspectives about the role of the extracellular
      matrix and membrane components in seed germination.

PMID- 22476455
TI  - TOPLESS co-repressor interactions and their evolutionary conservation in plants.
AB  - Large-scale protein-protein interaction studies recently demonstrated that the
      Arabidopsis TPL/TPR family of transcriptional co-repressors is involved in a
      broad range of developmental processes. TPL/TPRs predominantly interact with
      transcription factors that contain repression domain (RD) sequences.
      Interestingly, RDs reported in the literature are quite diverse in sequence, yet
      TPL/TPRs interact with proteins containing all of the known motifs. These data
      lead us to conclude that the TPL/TPRs act as general repressors of gene
      transcription in plants. To investigate this further, we examined interactions
      between TPL/TPR proteins encoded by the moss Physcomitrella patens genome and
      components of the auxin signaling pathway. As in Arabidopsis, moss TPL proteins
      interact with AUX/IAA and ARF proteins, suggesting that they act in both forms of
      ARF-mediated transcriptional repression. These data suggest that the involvement
      of TPL in auxin signaling has been conserved across evolution, since mosses and
      angiosperms diverged approximately 450 million years ago.

PMID- 22476456
TI  - Control and consequences of chromatin compaction during seed maturation in
      Arabidopsis thaliana.
AB  - Nuclei in dry Arabidopsis thaliana seeds are very small and have highly condensed
      chromatin. Nuclear shrinkage and chromatin compaction occur during seed
      maturation and have been shown to be independent, developmentally controlled
      processes. To confirm this genetically, we studied chromatin compaction in a
      mutant of the seed developmental regulator ABA INSENSITIVE 3, and in a double
      mutant of the nuclear matrix proteins LITTLE NUCLEI 1 and 2. Our results
      indicated that the nuclear shrinking and chromatin condensation during seed
      maturation can be genetically uncoupled, confirming that these are independent
      processes. In addition, we demonstrated that transcript levels of siliques toward
      the end of seed maturation are comparable to those in vegetative tissues, despite
      the highly compacted chromatin, small nuclear volume and low hydration status of
      seeds.

PMID- 22476457
TI  - Biochemical characterization of xylan xylosyltransferases involved in wood
      formation in poplar.
AB  - The major polysaccharides in dicot wood biomass are cellulose and xylan. Although
      wood-associated cellulose synthase genes responsible for cellulose biosynthesis
      have been characterized, wood-associated xylan synthase genes have not been
      biochemically identified. A recent report by Lee et al. (2012) provides the first
      biochemical evidence that two functionally non-redundant Arabidopsis GT43 members
      are xylosyltransferases (XylTs) that function cooperatively in the elongation of
      the xylan backbone. We further extend this finding in the current report
      demonstrating that two poplar (Populus trichocarpa) GT43 glycosyltransferases,
      PtrGT43B and PtrGT43C, are xylan XylTs involved in wood formation. We show that
      microsomes from transgenic tobacco BY2 cells coexpressing PtrGT43B and PtrGT43C
      exhibited a high XylT activity capable of generating beta-(1,4)-linked
      xylooligosaccharides, whereas little XylT activity was detected in microsomes
      with expression of PtrGT43B or PtrGT43C alone. These findings indicate that
      poplar GT43 members are XylTs that act cooperatively in catalyzing the successive
      transfer of xylosyl residues during xylan backbone biosynthesis, which provides
      further support of the hypothesis that the biochemical functions of GT43 members
      in vascular plants are evolutionarily conserved.

PMID- 22476458
TI  - Induction of IRT1 by the nickel-induced iron-deficient response in Arabidopsis.
AB  - Excessive amounts of nickel (Ni) can be toxic for plants. Recently, we reported
      that IRT1, the primary iron (Fe) uptake transporter in roots, meditates excess Ni
      accumulation in Arabidopsis thaliana. We also found that Ni exposure increases
      IRT1 expression in roots, suggesting that Ni uptake is further induced by Ni
      stress. Here, we show that Ni exposure induces expression of not only IRT1, but
      also FRO2, a ferric reductase in the root epidermis, and FIT, a transcription
      factor regulating the expression of genes involved in Fe homeostasis including
      IRT1 and FRO2. This result suggests that Ni accumulation induces an Fe-deficient
      response and leads to the induction of IRT1. Our findings suggest that excess Ni
      causes Fe deficiency at the molecular level and induces Fe deficiency signaling
      in plant cells.

PMID- 22476459
TI  - Never say dye: new roles for an old fluorochrome.
AB  - Recent years have seen a remarkable increase in the number of publications
      dealing with the application of epifluorescence microscopy in cell biology. This
      can be widely attributed to the development of state-of-the-art image processing
      programs, as well as the development of new reagents/probes, which allow the
      labeling of most cell structures, organelles and metabolites with high
      specificity. However, the use of a specific fluorescent dye, 3,3'
      dihexyloxacarbocyanine iodide (DiOC6), has been recently revisited and several
      new application potentials have emerged. The goal of this mini-review is to
      provide an up-to-date overview of the multiple roles of this multifaceted probe.

PMID- 22476460
TI  - Models for the mechanism for activating copper-zinc superoxide dismutase in the
      absence of the CCS Cu chaperone in Arabidopsis.
AB  - Copper-zinc superoxide dismutase (CuZnSOD; CSD) is an important antioxidant
      enzyme for oxidative stress protection. To date, two activation pathways have
      been identified in many species. One requiring the CCS, Cu chaperone for SOD, to
      insert Cu and activate CSD (referred to as CCS-dependent pathway), and the other
      works independently of CCS (referred to as CCS-independent pathway). In our
      previous study, we suggest an unidentified factor will work with glutathione
      (GSH) for CSD activation in the absence of the CCS. Here, two models of the CCS
      independent mechanism are proposed. The role of the unidentified factor may work
      as a scaffold protein, which provides a platform for the CSD protein and Cu-GSH
      to interact, or as a Cu carrier, which itself can bind Cu and interact with CSD
      proteins. We also suggest that the CSD protein conformation at C-terminal is
      important in providing a docking site for unidentified factor to access.

PMID- 22476461
TI  - Bioremoval capacity of three heavy metals by some microalgae species (Egyptian
      Isolates).
AB  - Three fresh water microalgal isolates [Phormidium ambiguum (Cyanobacterium),
      Pseudochlorococcum typicum and Scenedesmus quadricauda var quadrispina
      (Chlorophyta)] were tested for tolerance and removal of mercury (Hg2+), lead
      (Pb2+) and cadmium (Cd2+) in aqueous solutions as a single metal species at conc.
      5-100 mg/L under controled laboratory conditions. The obtained results showed
      that Hg2+ was the most toxic of the three metal ions to the test algae even at
      low concentration (< 20 mg/L). While lower concentration of Pb2+ and Cd2+ (5-20
      mg/L) enhanced the algal growth (chlorophyll a and protein), elevated
      concentrations (40-100 mg/L) were inhibitory to the growth. The results also
      revealed that Ph. ambiguum was the most sensitive alga to the three metal ions
      even at lower concentrations (5 and 10 mg/L) while P. typicum and S. quadricauda
      were more tolerant to high metal concentrations up to 100 mg/L. The bioremoval of
      heavy metal ions (Hg2+, Pb2+ and Cd2+) by P. typicum from aqueous solution showed
      that the highest percentage of metal bioremoval occurred in the first 30 min of
      contact recording 97% (Hg2+), 86% (Cd2+) and 70% (Pb2+). Transmission electron
      microscopy (TEM) was used to study the interaction between heavy metal ions and
      P. typicum cells. At ultrastructural level, an electron dense layers were
      detected on the algal cell surfaces when exposed to Cd, Hg and Pb. At the same
      time, dark spherical electron dense bodies were accumulated in the vacuoles of
      the algal cells exposed to Pb. Excessive accumulation of starch around the
      pyrenoids were recorded as well as deteriorations of the algal cell organelles
      exposed to the three metal ions.

PMID- 22476462
TI  - The chaperonin CCT8 facilitates spread of tobamovirus infection.
AB  - The homeodomain transcription factor KNOTTED1 (KN1) functions in shoot meristem
      maintenance and is thought to move from cell to cell in a similar fashion as
      viral movement proteins. Both types of transported proteins bind to RNA, and
      associate with intercellular bridges formed by plasmodesmata. In a mutant screen
      for KN1 transport deficiency, a component of a type II chaperonin complex, CCT8,
      was identified, and found to interact with non-cell-autonomous proteins. The cct8
      mutants are characterized by limited functionality of non-cell-autonomous
      proteins after their movement, and a phenotype resembling lack of homeodomain
      protein activity. Evidence suggests that CCT8 functions in post-translocational
      refolding of transported proteins. Here we show that spread of tobamovirus
      infection is reduced in a cct8 mutant. This suggests that similar to KN1, viral
      movement proteins are unfolded and refolded during transport to gain
      functionality in the receiving cells.

PMID- 22476463
TI  - Paranoid potato: phytophthora-resistant genotype shows constitutively activated
      defense.
AB  - Phytophthora is the most devastating pathogen of dicot plants. There is a need
      for resistance sources with different modes of action to counteract the fast
      evolution of this pathogen. In order to better understand mechanisms of defense
      against P. infestans, we analyzed several clones of potato. Two of the genotypes
      tested, Sarpo Mira and SW93-1015, exhibited strong resistance against P.
      infestans in field trials, whole plant assays and detached leaf assays. The
      resistant genotypes developed different sizes of hypersensitive response (HR)
      related lesions. HR lesions in SW93-1015 were restricted to very small areas,
      whereas those in Sarpo Mira were similar to those in Solanum demissum, the main
      source of classical resistance genes. SW93-1015 can be characterized as a cpr
      (constitutive expressor of PR genes) genotype without spontaneous microscopic or
      macroscopic HR lesions. This is indicated by constitutive hydrogen peroxide
      (H2O2) production and PR1 (pathogenesis-related protein 1) secretion. SW93-1015
      is one of the first plants identified as having classical protein-based induced
      defense expressed constitutively without any obvious metabolic costs or
      spontaneous cell death lesions.

PMID- 22476464
TI  - Barley tolerance of Russian wheat aphid (Hemiptera: Aphididae) biotype 2
      herbivory involves expression of defense response and developmental genes.
AB  - The Russian wheat aphid, Diuraphis noxia (Kurdjumov), is an invasive insect pest
      that causes serious yield losses in bread wheat, Triticum aestivum L., durum
      wheat, T. turgidum L and barley, Hordeum vulgare L. Successful management of D.
      noxia has been achieved through resistant varieties via plant antixenosis (aphid
      non-preference), antibiosis (reduced aphid growth or fecundity), tolerance (plant
      compensatory growth after aphid feeding), or a combination of each. Previous
      phenotyping experiments revealed that plants of the variety Stoneham resist D.
      noxia damage via tolerance. In the present study, genes involved in upstream
      regulation of jasmonic acid (JA), salicylic acid (SA), ethylene (ET), auxin (AUX)
      and abscisic acid (ABA) biosynthetic pathways were monitored using qRT-PCR in
      Stoneham and susceptible Otis barley plants after D. noxia biotype 2 feeding.
      Results indicate that D. noxia tolerance in Stoneham plants is related to greater
      constitutive expression of JA-, ET- and AUX-biosynthetic pathway genes than in
      susceptible Otis plants, suggesting the possibility of immediate plant
      adjustments due to the stress of D. noxia feeding. There was limited induction of
      genes in the ET-(ACCS) and IAA (TDC) pathways in Stoneham tissues after D. noxia
      feeding. JA pathway genes upregulated in Otis tissues after D. noxia infestation
      failed to successfully defend Otis plants. AUX and ABA transcripts in Otis may be
      associated with developmental collapses resulting from source and sink adjustment
      failures.

PMID- 22476465
TI  - Insights into the toxicity mechanism of and cell response to the herbicide 2,4-D
      in plants.
AB  - Although structurally similar to the natural plant hormone indol-3- acetic acid,
      auxin herbicides were developed for purposes other than growth, and have been
      successfully used in agriculture for the last 60 years. Concerted efforts are
      being made to understand and decipher the precise mechanism of action of IAA and
      synthetic auxins. Innumerable results need to be interconnected to resolve the
      puzzle of auxin biology and action mode of auxin herbicides. To date, different
      breakthroughs are providing more insights into the process of plant-herbicide
      interactions. Here we highlight some of the latest findings on how the 2,4
      dichlorophenoxyacetic acid damages susceptible broadleaf plants, emphasizing the
      role of ROS as a downstream component of the auxin signal transduction under
      herbicide treatment.

PMID- 22476466
TI  - SHORT-ROOT regulates vascular patterning, but not apical meristematic activity in
      the Arabidopsis root through cytokinin homeostasis.
AB  - SHORT-ROOT (SHR) is a key regulator of radial patterning and stem-cell renewal in
      the Arabidopsis root. Although SHR is expressed in the stele, its function in the
      vascular tissue was not recognized until recently. In shr, the protoxylem is
      missing due to the loss of expression of microRNA165A (miR165A) and microRNA166B
      (miR165B). shr is also defective in lateral root formation, but the mechanism
      remains unclear. To dissect the SHR developmental pathway, we recently have
      identified its direct targets at the genome scale by chromatin
      immunoprecipitation followed by microarray analysis (ChIP-chip). In further
      studies, we have shown that SHR regulates cytokinin homeostasis through cytokinin
      oxidase 3 and that this role of SHR is critical to vascular patterning in the
      root. In this communication we report that SHR also regulates miR165A and miR166B
      indirectly through its effect on cytokinin homeostasis. Although cytokinin is
      inhibitory to root growth, the root-apical-meristem defect in shr was not
      alleviated by reduction of endogenous cytokinin. These results together suggest
      that SHR regulates vascular patterning, but not root apical meristematic
      activity, through cytokinin homeostasis.

PMID- 22476467
TI  - Analysis of protein transport in the Brassica oleracea vasculature reveals
      protein-specific destinations.
AB  - We investigated the vascular transport properties of exogenously applied proteins
      to Brassica oleracea plants and compared their delivery to various aerial parts
      of the plant with carboxy fluorescein (CF) dye. We identified unique properties
      for each protein. Alexafluor-tagged bovine serum albumin (Alexa-BSA) and
      Alexafluor-tagged Histone H1 (Alexa-Histone) moved slower than CF dye throughout
      the plant. Interestingly, Alexa-Histone was retained in the phloem and phloem
      parenchyma while Alexa-BSA moved into the apoplast. One possibility is that Alexa
      Histone sufficiently resembles plant endogenous proteins and is retained in the
      vascular stream, while Alexa-BSA is exported from the cell as a foreign protein.
      Both proteins diffuse from the leaf veins into the leaf lamina. Alexa-BSA
      accumulated in the leaf epidermis while Alexa-Histone accumulated mainly in the
      mesophyll layers. Fluorescein-tagged hepatitis C virus core protein (fluorescein
      HCV) was also delivered to B. oleracea plants and is larger than Alexa-BSA. This
      protein moves more rapidly than BSA through the plant and was restricted to the
      leaf veins. Fluorescein-HCV failed to unload to the leaf lamina. These combined
      data suggest that there is not a single default pathway for the vascular transfer
      of exogenous proteins in B. oleracea plants. Specific protein properties appear
      to determine their destination and transport properties within the phloem.

PMID- 22476468
TI  - Arabidopsis purple acid phosphatase 10 is a component of plant adaptive mechanism
      to phosphate limitation.
AB  - When grown with inadequate quantities of inorganic phosphate (Pi), plants
      synthesize and secret acid phosphatases into the rhizosphere. These secreted acid
      phosphatases are thought to release the Pi group from organophosphates present in
      the surrounding environment and to thereby increase Pi availability to plants. So
      far, however, the genetic evidence to support this hypothesis is still lacking.
      Previously, we showed that overexpression of Arabidopsis purple acid phosphatase
      10 (AtPAP10) improved the growth of plants on Pi-deficient medium (P- medium)
      supplemented with the organophosphate compound ADP; in contrast, the growth of
      atpap10 mutant lines was reduced on the same medium. In the current research, we
      determined the growth performance of these lines on P- medium supplemented with
      four other organophosphates. The results showed that AtPAP10 could utilize
      rhizosphere organophosphates other than ADP for plant growth but with different
      utilization efficiencies. This work provides further genetic evidence that
      AtPAP10 phosphatase is a component of plant adaptive mechanism to Pi limitation.

PMID- 22476469
TI  - Tissue localization of maize acetylcholinesterase associated with heat tolerance
      in plants.
AB  - Our recent study reported that maize acetylcholinesterase (AChE) activity in the
      coleoptile node is enhanced through a post-translational modification response to
      heat stress and transgenic plants overexpressing maize AChE gene had an elevated
      heat tolerance, which strongly suggests that maize AChE plays a positive,
      important role in maize heat tolerance. Here we present (1) maize AChE activity
      in the mesocotyl also enhances during heat stress and (2) maize AChE mainly
      localizes in vascular bundles including endodermis and epidermis in coleoptile
      nodes and mesocotyls of maize seedlings.

PMID- 22476470
TI  - The histological growth pattern of colorectal cancer liver metastases has
      prognostic value.
AB  - Little is known about the biological characteristics that determine the prognosis
      of colorectal cancer (CRC) liver metastases. In previous work we reported three
      different histological patterns of the tumour-liver interface of CRC liver
      metastases, termed the pushing, replacement and desmoplastic growth pattern (GP).
      The purpose of this study was to confirm differences in angiogenic and hypoxic
      properties of CRC liver metastases with different GPs in a large data set and to
      study the value of the GP as a prognostic factor. In 205 patients undergoing a
      resection of CRC liver metastases, the GP of the metastasis was determined using
      haematoxylin-eosin and Gordon Sweet's silver staining. The tumour cell
      proliferation fraction (TCP%), endothelial cell proliferation fraction (ECP%) and
      carbonic anhydrase 9 (CA9) expression were determined using immunohistochemistry.
      Standard clinicopathological data and overall survival were recorded. 27.8, 15.6,
      34.6 and 17.6 % of liver metastases had a replacement, pushing, desmoplastic and
      mixed GP, respectively. Analyses of TCP%, ECP% and CA9 expression demonstrated
      that CRC liver metastases with a replacement GP are non-angiogenic, while the
      ones with a pushing GP are the most angiogenic with angiogenesis being, at least
      partially, hypoxia-driven. GP (pushing or not) was the only independent predictor
      of survival at 2 years. CRC liver metastases grow according to different GP
      patterns with different angiogenic properties. At 2 years of follow-up a GP with
      a pushing component was an independent predictor of poor survival, suggesting
      that the pushing GP is characterized by a more aggressive tumour biology. Further
      elucidation of the mechanisms and biological pathways involved in and responsible
      for the differences in GP between CRC liver metastases in different patients
      might lead to therapeutic agents and strategies taking advantage of this 2 year
      'window of opportunity'.

PMID- 22476471
TI  - Venous thromboembolism prevention with fondaparinux 1.5 mg in renally impaired
      patients undergoing major orthopaedic surgery. A real-world, prospective,
      multicentre, cohort study.
AB  - Despite the need for effective and safe thromboprophylactic drugs for patients
      with renal impairment, clinical trial data on anticoagulant agents are limited in
      this population. The study aim was to assess in the real-world setting the use of
      the once-daily 1.5 mg reduced dosage regimen of fondaparinux available for this
      context. In this prospective cohort study, patients with a creatinine clearance
      (CrCl) of 20-50 ml/minute, undergoing total hip (THR) or knee (TKR) replacement
      or hip fracture surgery (HFS) received fondaparinux thromboprophylaxis. Main
      clinical outcomes were bleeding (major/clinically relevant non-major),
      symptomatic venous thromboembolism (VTE) and death. Overall, 442 patients (353
      women; median age: 82 years; 39.4% in ASA class >=3; mean +/- SD CrCl: 39.0 +/-
      8.0 ml/minute; 78% with additional risk factors for bleeding), undergoing THR
      (43.7%), TKR (27.6%), or HFS (28.7%) received fondaparinux 1.5 mg for a mean +/-
      SD duration of 16.0 +/- 12.5 days. At postoperative day 10, the rates (95%
      confidence interval) of major bleeding, clinically relevant bleeding and
      symptomatic VTE were 4.5% (2.8-6.9), 0.5% (0.1-1.6) and 0.5% (0.05-1.62),
      respectively; no fatal bleeding, bleeding into a critical organ, pulmonary
      embolism or proximal deep-vein thrombosis occurred. Corresponding rates at one
      month were 5.2%, 0.7% and 0.7%. One-month mortality was 2.3% (0.9-3.6). This
      large clinical prospective study provides for the first time, under conditions
      reflecting "real-world" routine clinical practice, data on the bleeding and VTE
      risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopaedic
      surgery in renally impaired patients. It shows that these patients constitute a
      very elderly and fragile population.

PMID- 22476472
TI  - Estimates of nuclear DNA content in 98 species of brown algae (Phaeophyta).
AB  - BACKGROUND AND AIMS: Brown algae are critical components of marine ecosystems
      around the world. However, the genome of only one species of the class has so far
      been sequenced. This contrasts with numerous sequences available for model
      organisms such as higher plants, flies or worms. The present communication
      expands our coverage of DNA content information to 98 species of brown algae with
      a view to facilitating further genomic investigations of the class. METHODOLOGY:
      The DNA-localizing fluorochrome DAPI (4',6-diamidino-2-phenylindole) and the red
      blood cell (chicken erythrocyte) standard were used to estimate 2C values by
      static microspectrophotometry. PRINCIPAL RESULTS: 2C DNA contents are reported
      for 98 species of brown algae, almost doubling the number of estimates available
      for the class. The present results also expand the reported DNA content range to
      0.2-3.6 pg, with several species of Fucales and Laminariales containing apparent
      polyploid genomes with 2C = 1.8-3.6 pg. CONCLUSIONS: The data provide DNA content
      values for 12 of the 19 recognized orders of brown algae spanning the breadth of
      the class. Despite earlier contentions concerning DNA content and the presence of
      oogamy, the present results do not support a correlation between phylogenetic
      placement and genome size. The closest sister groups to the brown algae have
      genome sizes on the order of 0.3 pg (e.g. Schizocladiophyceae), suggesting that
      this may be the ancestral genome size. However, DNA content ranges widely across
      the class.

PMID- 22476473
TI  - Association of leaf micro-morphological characters with powdery mildew resistance
      in field-grown mulberry (Morus spp.) germplasm.
AB  - BACKGROUND AND AIMS: Micro-morphological characteristics can influence fungal
      infectivity. We sought links between micro-morphology and resistance to powdery
      mildew in mulberry with the intention of assisting selection of disease-resistant
      lines. METHODOLOGY: Over 3 years and under field conditions, we evaluated 30
      lines of mulberry with contrasting susceptibilities to powdery mildew (15
      resistant and 15 susceptible). Disease severity was related statistically to
      stomatal area, stomatal density, stomatal index, upper and lower cuticular
      thicknesses, leaf thickness and trichome density. PRINCIPAL RESULTS: Differences
      between lines were significant (P <0.05) for all characters studied. Variation
      between the resistant and susceptible groups was statistically highly significant
      (P <0.01) for stomatal index, stomatal area and trichome density. The powdery
      mildew-resistant group was distinguished by  17.4 % lower stomatal density, 12.5
      % smaller stomatal index per unit leaf area, 20.0 % greater trichome density and
      18.0 % higher stomatal area compared with the susceptible group. Trichome density
      was negatively correlated with disease severity index and with the accumulative
      area under disease progression curves. Stomatal density was positively correlated
      with both measures of disease severity. Although stomatal area was negatively
      related to disease severity index (r = -0.28; P <0.05), the correlation was weak.
      There was no statistically significant relationship between stomatal area and the
      accumulative area under disease progression curves. The germplasm was partitioned
      into seven sub-groups based on hierarchical cluster analysis derived from pooled
      disease severity index scores and three highly significant micro-morphological
      characters. Eighty per cent of the resistant germplasm accumulated in three
      cluster components (A1, A2 and B2) characterized by high trichome densities and a
      high stomatal density and stomatal index. CONCLUSIONS: Resistance to powdery
      mildew in mulberry is associated with trichome and stomatal features rather than
      leaf and epidermal thicknesses. Trichome density, stomatal density and stomatal
      index are shown to be promising markers for screening powdery mildew resistance
      in breeding programmes.

PMID- 22476474
TI  - High genetic diversity with moderate differentiation in Juniperus excelsa from
      Lebanon and the eastern Mediterranean region.
AB  - BACKGROUND AND AIMS: Juniperus excelsa is an important woody species in the high
      mountain ecosystems of the eastern Mediterranean Basin where it constitutes the
      only coniferous species found at the tree line. The genetic diversity within and
      among J. excelsa populations of the eastern Mediterranean Basin is studied in the
      light of their historical fragmentation. METHODOLOGY: Nuclear microsatellites
      originally developed for Juniperus communis and J. przewalskii were tested on 320
      individuals from 12 different populations originating from Lebanon, Turkey,
      Cyprus, Greece and the Ukraine. PRINCIPAL RESULTS: Among the 31 nuclear
      microsatellite primers tested, only three produced specific amplification
      products, with orthology confirmed by sequence analysis. They were then used for
      genetic diversity studies. The mean number of alleles and the expected
      heterozygosity means were N(a)=8.78 and H(e)=0.76, respectively. The fixation
      index showed a significant deviation from Hardy-Weinberg equilibrium and an
      excess of homozygotes (F(IS)=0.27-0.56). A moderate level of genetic
      differentiation was observed among the populations (F(ST)=0.075, P<0.001). The
      most differentiated populations corresponded to old vestigial stands found at the
      tree line (>2000 m) in Lebanon. These populations were differentiated from the
      other populations that are grouped into three sub-clusters. CONCLUSIONS: High
      levels of genetic diversity were observed at species and population levels. The
      high level of differentiation in the high-mountain Lebanese populations reflects
      a long period of isolation or possibly a different origin. The admixture observed
      in other populations from Lebanon suggests a more recent separation from the
      Turkish-southeastern European populations.

PMID- 22476475
TI  - Image use in field guides and identification keys: review and recommendations.
AB  - BACKGROUND AND AIMS: Although illustrations have played an important role in
      identification keys and guides since the 18th century, their use has varied
      widely. Some keys lack all illustrations, while others are heavily illustrated.
      Even within illustrated guides, the way in which images are used varies
      considerably. Here, we review image use in paper and electronic guides, and
      establish a set of best practices for image use in illustrated keys and guides.
      SCOPE: Our review covers image use in both paper and electronic guides, though we
      only briefly cover apps for mobile devices. With this one exception, we cover the
      full range of guides, from those that consist only of species descriptions with
      no keys, to lavishly illustrated technical keys. Emphasis is placed on how images
      are used, not on the operation of the guides and key, which has been reviewed by
      others. We only deal with operation when it impacts image use. MAIN POINTS: Few
      illustrated keys or guides use images in optimal ways. Most include too few
      images to show taxonomic variation or variation in characters and character
      states. The use of multiple images allows easier taxon identification and
      facilitates the understanding of characters. Most images are usually not
      standardized, making comparison between images difficult. Although some
      electronic guides allow images to be enlarged, many do not. CONCLUSIONS: The best
      keys and guides use standardized images, displayed at sizes that are easy to see
      and arranged in a standardized manner so that similar images can be compared
      across species. Illustrated keys and glossaries should contain multiple images
      for each character state so that the user can judge variation in the state.
      Photographic backgrounds should not distract from the subject and, where
      possible, should be of a standard colour. When used, drawings should be prepared
      by professional botanical illustrators, and clearly labelled. Electronic keys and
      guides should allow images to be enlarged so that their details can be seen.

PMID- 22476476
TI  - Principles of visual key construction-with a visual identification key to the
      Fagaceae of the southeastern United States.
AB  - BACKGROUND AND AIMS: Advances in digital imaging have made possible the creation
      of completely visual keys. By a visual key we mean a key based primarily on
      images, and that contains a minimal amount of text. Characters in visual keys are
      visually, not verbally defined. In this paper we create the first primarily
      visual key to a group of taxa, in this case the Fagaceae of the southeastern USA.
      We also modify our recently published set of best practices for image use in
      illustrated keys to make them applicable to visual keys. METHODOLOGY: Photographs
      of the Fagaceae were obtained from internet and herbarium databases or were taken
      specifically for this project. The images were printed and then sorted into
      hierarchical groups. These hierarchical groups of images were used to create the
      'couplets' in the key. A reciprocal process of key creation and testing was used
      to produce the final keys. PRINCIPAL RESULTS: Four keys were created, one for
      each of the parts-leaves, buds, fruits and bark. Species description pages
      consisting of multiple images were also created for each of the species in the
      key. Creation and testing of the key resulted in a modified list of best
      practices for image use visual keys. CONCLUSIONS: The inclusion of images into
      paper and electronic keys has greatly increased their ease of use. However,
      virtually all of these keys are still based upon verbally defined, atomistic
      characters. The creation of primarily visual keys allows us to overcome the well
      known limitations of linguistic-based characters and create keys that are much
      easier to use, especially for botanical novices.

PMID- 22476477
TI  - How much detail and accuracy is required in plant growth sub-models to address
      questions about optimal management strategies in agricultural systems?
AB  - BACKGROUND AND AIMS: Simulations that integrate sub-models of important
      biological processes can be used to ask questions about optimal management
      strategies in agricultural and ecological systems. Building sub-models with more
      detail and aiming for greater accuracy and realism may seem attractive, but is
      likely to be more expensive and time-consuming and result in more complicated
      models that lack transparency. This paper illustrates a general integrated
      approach for constructing models of agricultural and ecological systems that is
      based on the principle of starting simple and then directly testing for the need
      to add additional detail and complexity. METHODOLOGY: The approach is
      demonstrated using LUSO (Land Use Sequence Optimizer), an agricultural system
      analysis framework based on simulation and optimization. A simple sensitivity
      analysis and functional perturbation analysis is used to test to what extent
      LUSO's crop-weed competition sub-model affects the answers to a number of
      questions at the scale of the whole farming system regarding optimal land-use
      sequencing strategies and resulting profitability. PRINCIPAL RESULTS: The need
      for accuracy in the crop-weed competition sub-model within LUSO depended to a
      small extent on the parameter being varied, but more importantly and
      interestingly on the type of question being addressed with the model. Only a
      small part of the crop-weed competition model actually affects the answers to
      these questions. CONCLUSIONS: This study illustrates an example application of
      the proposed integrated approach for constructing models of agricultural and
      ecological systems based on testing whether complexity needs to be added to
      address particular questions of interest. We conclude that this example clearly
      demonstrates the potential value of the general approach. Advantages of this
      approach include minimizing costs and resources required for model construction,
      keeping models transparent and easy to analyse, and ensuring the model is well
      suited to address the question of interest.

PMID- 22476478
TI  - Seed pre-treatment in rice reduces damage, enhances carbohydrate mobilization and
      improves emergence and seedling establishment under flooded conditions.
AB  - BACKGROUND AND AIMS: Early flooding helps control weeds but reduces seedling
      establishment in direct-seeded rice (Oryza sativa). When combined with
      appropriate management practices, the use of genotypes that better tolerate
      flooding during emergence can enhance crop establishment in flood-prone areas.
      Management options include seed pre-treatment and we tested the influence of pre
      soaking for 24 h prior to sowing or of priming (soaking for 24 or 48 h followed
      by drying). METHODOLOGY: The effects on seedling establishment after 21-day
      flooding of pre-soaking seeds for 24 h before sowing and/or of priming seeds were
      examined together with physiological responses connected with reactive oxygen
      scavenging. Seeds of four lines with contrasting abilities to tolerate flooding
      at the germination stage were compared. Seeds were primed using KCl solutions (48
      h) or water (24 h) and pre-soaked using water. Lipid peroxidation and activities
      of reactive oxygen-scavenging enzymes were measured in seeds before sowing.
      Carbohydrate mobilization in germinating seeds and seedling growth were also
      monitored at intervals. PRINCIPAL RESULTS: Seed pre-treatment by pre-soaking or
      by priming increased survival of flooding and accelerated and improved seedling
      establishment, especially in tolerant genotypes. Primed seeds had less lipid
      peroxidation and higher superoxide dismutase (SOD) and catalase (CAT) activities
      than non-primed seeds. Amylase activities and starch breakdown were also hastened
      in primed seeds. Survival after flooding was positively correlated with amylase
      activity but negatively correlated with the extent of lipid peroxidation.
      CONCLUSIONS: Pre-soaking and priming improved seedling establishment in flooded
      soil, enhanced the capacity to scavenge reactive oxygen species in seeds by
      increasing SOD and CAT activities, and hastened carbohydrate mobilization.
      Tolerant genotypes responded better to these treatments, emphasizing the
      effectiveness of combining genetic tolerance with appropriate seed pre-treatment
      to improve seedling establishment of rice sown in flooded soils.

PMID- 22476479
TI  - Detection and analysis of endogenous badnaviruses in the New Zealand flora.
AB  - BACKGROUND AND AIMS: Badnaviruses and their host-integrated DNA occur in tropical
      crops and a few northern temperate species. Following the discovery of a
      badnavirus on a subantarctic island with floristic links to New Zealand, we
      postulated that badnaviruses exist in the New Zealand flora. Badnavirus reverse
      transcriptase (RT) sequences consist of variable regions flanked by highly
      conserved regions. This study used RT sequences to detect and characterize
      badnavirus sequences in the New Zealand flora and to investigate their utility
      for the study of broader aspects of plant biology. METHODOLOGY: Molecular
      diversity of RT sequences was analysed using polymerase chain reaction and
      denaturing gradient gel electrophoresis (DGGE). In a study of the genus
      Melicytus, internal transcribed spacer (ITS) sequences were compared with the RT
      data. PRINCIPAL RESULTS: No freely replicating badnaviruses were detected but
      more than half of the species (37/60) contained RT sequences. Phylogenetic
      analysis of 21 RT sequences formed monophyletic groups distinct from other
      species and from badnaviruses. No frameshift mutations occurred in any of the
      sequences translated in silico. More detailed study of the genus Melicytus
      indicated broader applications for our approach. Analysis of RT sequences
      revealed the presence of a previously unrecognized species (confirmed using ITS).
      Inheritance of DGGE profiles by Melicytus ramiflorus seedlings suggested that
      this species may undergo apomixis. CONCLUSIONS: The presence of integrated
      badnavirus sequences in a wide range of taxa from this Southern Hemisphere flora
      indicates that these sequences may be common in many temperate regions. Potential
      to activate viruses from these sequences should be considered when placing these
      species in tissue culture or under other forms of abiotic or genomic stress.
      Analysis of endogenous RT sequences shows potential for the study of systematics,
      phylogenetics and plant reproductive biology.

PMID- 22476480
TI  - Equisetum species show uniform epicuticular wax structures but diverse
      composition patterns.
AB  - BACKGROUND AND AIMS: Only few data on the epicuticular waxes (EWs) of horsetails
      are available. This contribution therefore focuses on the wax micromorphology and
      chemical composition of Equisetum species of the subgenera Equisetum and
      Hippochaete. METHODOLOGY: Distribution patterns and structural details of EW on
      the shoots were studied by scanning electron microscopy. After extraction with
      chloroform, the chemical composition of wax isolates was analysed by gas
      chromatography. PRINCIPAL RESULTS: Epicuticular wax crystals were non-oriented
      platelets or membraneous platelets. They were usually located on subsidiary cells
      of stomata and adjacent cells. Other parts of the shoots were covered mainly with
      a smooth wax film or small granules only. The chemical constituents found were
      alkanes, esters, aldehydes, primary alcohols and free fatty acids in a range of
      C(20)-C(36) (in esters C(36)-C(56)). All species of the subgenus Hippochaete
      showed a similar pattern of fractions with high percentages of alkanes and
      aldehydes, whereas the subgenus Equisetum species had distinctly different wax
      compositions. Extracts from the internodes-surfaces without well-developed EW
      crystals and only few stomata-showed the lowest contents of aldehydes.
      CONCLUSIONS: The covering with EW crystals will provide unhindered gas exchange
      and, combined with intracuticular wax, may prevent excess water loss during
      winter in the evergreen shoots of the subgenus Hippochaete. The results indicate
      that the Equisetum wax micromorphology and biosynthesis are comparable to EW of
      other pteridophyte classes and mosses.

PMID- 22476481
TI  - Expanding the docosahexaenoic acid food web for sustainable production:
      engineering lower plant pathways into higher plants.
AB  - BACKGROUND: Algae are becoming an increasingly important component of land plant
      metabolic engineering projects. Land plants and algae have similar enough
      genetics to allow relatively straightforward gene transfer and they also share
      enough metabolic similarities that algal enzymes often function in a plant cell
      environment. Understanding metabolic systems in algae can provide insights into
      homologous systems in land plants. As examples, algal models are currently being
      used by several groups to better understand starch and lipid metabolism and
      catabolism, fields which have relevance in land plants. Importantly, land plants
      and algae also have enough metabolic divergence that algal genes can often
      provide new metabolic traits to plants. Furthermore, many algal genomes have now
      been sequenced, with many more in progress, and this easy access to genome-wide
      information has revealed that algal genomes are often relatively simple when
      compared with plants. SCOPE: One example of the importance of algal, and in
      particular microalgal, resources to land plant research is the metabolic
      engineering of long-chain polyunsaturated fatty acids into oilseed crops which
      typically uses microalgal genes to extend existing natural plant biosynthetic
      pathways. This review describes both recent progress and remaining challenges in
      this field.

PMID- 22476482
TI  - Micropropagation of Ilex khasiana, a critically endangered and endemic holly of
      Northeast India.
AB  - BACKGROUND AND AIMS: Ilex khasiana is a rare and critically endangered holly
      endemic to the Khasi Hills of Meghalaya, India, and confined to a small number of
      pocket areas. In addition to conventional methods of propagation, endemic and
      threatened plants such as this could be more effectively multiplied and conserved
      using in vitro methods. Such techniques have the additional advantage of having a
      low impact on wild populations because they require a minimum of starting
      material. Our objective was to develop methodologies for the successful in vitro
      mass propagation of I. khasiana. METHODOLOGY: Seedlings were germinated in vitro
      under sterile conditions and nodal explants from these were transferred to
      Murashige and Skoog (MS) medium supplemented with 8.88 uM 6-benzyladenine and
      4.64 uM kinetin. PRINCIPAL RESULTS: This generated ~10 shoots per explant. In a
      second approach, callus was obtained from seedling-derived leaf discs cultured on
      MS medium supplemented with 2,4-dichlorophenoxyacetic acid and 6-benzyladenine.
      Approximately 12 adventitious shoots per callus were regenerated from 83.33 % of
      the calli after transfer to MS medium supplemented with 6.63 uM 6-benzyladenine.
      The most effective treatment for inducing root formation on the shoots was
      transfer of shoots to half-strength MS medium with 9.84 uM indole-3-butyric acid.
      Regenerated plantlets with well-developed shoots and roots were hardened and
      transferred to open soil with 70 % survival after 4 weeks. CONCLUSIONS: Both the
      methods described here are well suited for the mass multiplication of this
      critically endangered tree species.

PMID- 22476483
TI  - Phenotypic variation in heteroblastic woody species does not contribute to shade
      survival.
AB  - BACKGROUND AND AIMS: Leaf heteroblasty involves dramatic phenotypic differences
      between adult and seedling leaves while leaves of homoblastic plants display only
      small differences. This study tested whether, in low-light environments, the
      marked difference in the morphology of seedling leaves that characterizes
      heteroblastic species confers advantages for seedling survival and growth
      compared with homoblastic congeners. METHODOLOGY: Four pairs of heteroblastic and
      homoblastic species in genera Hoheria, Aristotelia, Pseudopanax and Melicope were
      grown in simulated full sunlight (100 % of light, red:far red ratio (R:FR) =
      1.25) or in simulated forest understorey shade (5 % of full sunlight, R:FR ratio
      = 0.25) in a glasshouse. PRINCIPAL RESULTS: After 9 months, 100 % of seedlings of
      both homoblastic and heteroblastic species survived in full sun while in the
      understorey treatment there were 25 % fewer heteroblastic survivors than
      homoblastic congeners. Compared with homoblastic congeners, all heteroblastic
      species except for Pseudopanax crassifolius produced more and smaller leaves and
      branches, but grew more slowly in height, root collar diameter and total biomass
      both in full sun and in forest understorey treatments. CONCLUSIONS: Homoblastic
      species survive and grow better in the forest understorey light treatment,
      suggesting that heteroblastic seedling leaf morphology does not give an advantage
      over homoblastic congeners under low light intensities.

PMID- 22476484
TI  - Reproductive phenology of 233 species from four herbaceous-shrubby communities in
      the Gran Sabana Plateau of Venezuela.
AB  - BACKGROUND AND AIMS: Herbaceous-shrubby communities in the Gran Sabana (Great
      Savanna) Plateau of Venezuela grow under non-zonal conditions. We speculated that
      this would produce specific patterns of reproductive phenology within these
      different soil-climate-vegetation associations. Specifically, we tested the
      hypothesis that the reproductive phenology patterns of four herbaceous-shrubby
      communities are determined by climate, plant life-forms and soil properties.
      METHODOLOGY: The reproductive phenology of 233 plant species of the Gran Sabana
      Plateau of the Venezuelan Guayana Highlands was studied taking into account their
      life-forms (i.e. trees, shrubs, climbers, annual herbs, perennial herbs,
      epiphytes and parasites/hemiparasites) in four herbaceous-shrubby communities:
      (i) shrubland, (ii) secondary bush, (iii) savanna and (iv) broad-leaved meadow.
      Patterns of flowering, and occurrence of unripe fruit and ripe fruit were studied
      at two levels of intensity for 24 months within a 5-year span. Two phenological
      records for each month of the year and between two and four replicates for each
      community type were made. Randomly selected 2-3 ha plots were used. General
      phenological patterns were established using <25% of the plants of each species
      in each plot to give the total duration of each phenological phase. High
      intensity phenological patterns were established using >25% of individuals in
      each plot to establish times of high abundance of flowers, and presence of unripe
      fruit and/or ripe fruit on individual plants. This generated phenological peaks
      for each species. PRINCIPAL RESULTS: Non-seasonality of general flowering and
      unripe fruiting in each of the four communities was related to non-seasonal
      flowering and unripe fruiting patterns in the plant life-forms studied and to low
      variation in precipitation throughout the year. Flowering activity in the
      shrubland and broad-leaved meadow peaked twice. The bush community had only one
      flowering peak while the savanna gave a non-seasonal flowering peak. The peak
      unripe fruiting pattern was not clearly related to unripe fruit phenological
      patterns of the most abundant life-forms. Unripe fruit patterns and precipitation
      were only correlated for shrubs, climbers and trees in the shrubland. Ripe
      fruiting patterns peaked during the short-dry season in the bush and shrubland,
      and were negatively correlated with precipitation in the shrubland. General and
      peak ripe fruiting patterns were non-seasonal in the savanna and broad-leaved
      meadow and related to the dominance of herbaceous species with prolonged ripe
      fruiting times, low climate seasonality, high plant species richness and
      diversity, and dispersal syndromes. CONCLUSIONS: The reproductive phenology of
      the herbaceous-shrubby communities is mainly influenced by the composition of the
      life-forms, the precipitation regime and soil type.

PMID- 22476485
TI  - Green love talks; cell-cell communication during double fertilization in
      flowering plants.
AB  - BACKGROUND: Flowering plant seeds originate from a unique double-fertilization
      event, which involves two sperm cells and two female gametes, the egg cell and
      the central cell. For many years our knowledge of mechanisms involved in
      angiosperm fertilization remained minimal. It was obvious that several signals
      were required to explain how the male gametes are delivered inside the maternal
      reproductive tissues to the two female gametes but their molecular nature
      remained unknown. The difficulties in imaging the double-fertilization process
      prevented the identification of the mode of sperm cell delivery. It was believed
      that the two sperm cells were not functionally equivalent. SCOPE: We review
      recent studies that have significantly improved our understanding of the early
      steps of double fertilization. The attractants of the pollen tube have been
      identified as small proteins produced by the synergid cells that surround the egg
      cell. Genetic studies have identified the signalling pathways required for the
      release of male gametes from the pollen tube. High-resolution imaging of the
      trajectory of the two male gametes showed that their transport does not involve
      the synergid cells directly and that isomorphic male gametes are functionally
      equivalent. We also outline major outstanding issues in the field concerned with
      the barrier against polyspermy, gamete recognition and mechanisms that prevent
      interspecies crosses.

PMID- 22476486
TI  - The amino terminal F-box domain of Petunia inflata S-locus F-box protein is
      involved in the S-RNase-based self-incompatibility mechanism.
AB  - BACKGROUND AND AIMS: Pistils of flowering plants possessing self-incompatibility
      (SI) can distinguish between self and non-self pollen, and only allow non-self
      pollen to effect fertilization. For Petunia inflata, the S-RNase gene encodes
      pistil specificity and multiple S-locus F-box (SLF) genes encode pollen
      specificity. Each SLF produced in pollen interacts with a subset of non-self S
      RNases to mediate their ubiquitination and degradation by the 26S proteasome.
      RATIONALE: S-locus F-box has been proposed to function as a component of the
      conventional SCF (SKP1-CULLIN-F-box protein) complex, based on the finding that
      two SKP1-like proteins, AhSSK1 (Antirrhinum hispanicum SLF-interacting SKP1
      like1) and PhSSK1 (Petunia hybrida SSK1), interact with the F-box domain of some
      allelic variants of SLF. However, we previously showed that PiSLF (P. inflata
      SLF) did not interact with any SKP1 of P. inflata or Arabidopsis thaliana, but
      instead interacted with a RING-finger protein, PiSBP1 (P. inflata S-RNase-Binding
      Protein1), which may also play the role of SKP1. Thus, the biochemical nature of
      the SLF-containing complex is as yet unclear. PRINCIPAL RESULTS: To examine
      whether the F-box domain of PiSLF is required for SI function, we expressed a
      truncated PiSLF(2) (S(2) allelic variant) without this domain in S(2)S(3) plants
      and showed that, unlike the full-length PiSLF(2), it did not cause breakdown of
      SI in S(3) pollen. We identified PiSSK1 (P. inflata SSK1) and found that it did
      not interact with PiSLF(1), PiSLF(2) or PiSLF(3). CONCLUSIONS: The finding that
      the truncated PiSLF(2) did not cause breakdown of SI in S(3) transgenic pollen
      suggests that the F-box domain of PiSLF(2) is required for mediating degradation
      of S(3)-RNase, a non-self S-RNase, in S(3) pollen, and thus is required for SI
      function. The finding that PiSSK1 did not interact with three allelic variants of
      PiSLF is consistent with our previous finding that PiSLF might not be in a
      conventional SCF complex.

PMID- 22476487
TI  - Receptor-like kinases as surface regulators for RAC/ROP-mediated pollen tube
      growth and interaction with the pistil.
AB  - BACKGROUND: RAC/ROPs are RHO-type GTPases and are known to play diverse
      signalling roles in plants. Cytoplasmic RAC/ROPs are recruited to the cell
      membrane and activated in response to extracellular signals perceived and
      mediated by cell surface-located signalling assemblies, transducing the signals
      to regulate cellular processes. More than any other cell types in plants, pollen
      tubes depend on continuous interactions with an extracellular environment
      produced by their surrounding tissues as they grow within the female organ pistil
      to deliver sperm to the female gametophyte for fertilization. SCOPE: We review
      studies on pollen tube growth that provide compelling evidence indicating that
      RAC/ROPs are crucial for regulating the cellular processes that underlie the
      polarized cell growth process. Efforts to identify cell surface regulators that
      mediate extracellular signals also point to RAC/ROPs being the molecular switches
      targeted by growth-regulating female factors for modulation to mediate
      pollination and fertilization. We discuss a large volume of work spanning more
      than two decades on a family of pollen-specific receptor kinases and some recent
      studies on members of the FERONIA family of receptor-like kinases (RLKs).
      SIGNIFICANCE: The research described shows the crucial roles that two RLK
      families play in transducing signals from growth regulatory factors to the
      RAC/ROP switch at the pollen tube apex to mediate and target pollen tube growth
      to the female gametophyte and signal its disintegration to achieve fertilization
      once inside the female chamber.

PMID- 22476488
TI  - Parentage determination of Vanda Miss Joaquim (Orchidaceae) through two
      chloroplast genes rbcL and matK.
AB  - BACKGROUND AND AIMS: The popular hybrid orchid Vanda Miss Joaquim was made
      Singapore's national flower in 1981. It was originally described in the
      Gardeners' Chronicle in 1893, as a cross between Vanda hookeriana and Vanda
      teres. However, no record had been kept as to which parent contributed the
      pollen. This study was conducted using DNA barcoding techniques to determine the
      pod parent of V. Miss Joaquim, thereby inferring the pollen parent of the hybrid
      by exclusion. METHODOLOGY: Two chloroplast genes, matK and rbcL, from five
      related taxa, V. hookeriana, V. teres var. alba, V. teres var. andersonii, V.
      teres var. aurorea and V. Miss Joaquim 'Agnes', were sequenced. The matK gene
      from herbarium specimens of V. teres and V. Miss Joaquim, both collected in 1893,
      was also sequenced. PRINCIPAL RESULTS: No sequence variation was found in the 600
      bp region of rbcL sequenced. Sequence variation was found in the matK gene of V.
      hookeriana, V. teres var. alba, V. teres var. aurorea and V. Miss Joaquim
      'Agnes'. Complete sequence identity was established between V. teres var.
      andersonii and V. Miss Joaquim 'Agnes'. The matK sequences obtained from the
      herbarium specimens of V. teres and V. Miss Joaquim were completely identical to
      the sequences obtained from the fresh samples of V. teres var. andersonii and V.
      Miss Joaquim 'Agnes'. CONCLUSIONS: The pod parent of V. Miss Joaquim 'Agnes' is
      V. teres var. andersonii and, by exclusion, the pollen parent is V. hookeriana.
      The herbarium and fresh samples of V. teres var. andersonii and V. Miss Joaquim
      share the same inferred maternity. The matK gene was more informative than rbcL
      and facilitated differentiation of varieties of V. teres.

PMID- 22476490
TI  - Chromosome number variation in two antipodean floras.
AB  - BACKGROUND AND AIMS: We compared chromosome number (CN) variation in the nearly
      antipodean Italian and New Zealand floras to verify (i) whether patterns of
      variation reflect their similar latitudinal ranges or their different
      biogeographic/taxonomic contexts, (ii) if any differences are equally distributed
      across major taxa/lineages and (iii) if the frequency, number and taxonomic
      distribution of B-chromosomes differ between the two countries. METHODOLOGY: We
      compared two datasets comprising 3426 (Italy) and 2525 (New Zealand) distinct
      cytotypes. We also compared a subset based on taxonomic orders and superimposed
      them onto a phylogeny of vascular plants. We used standard statistics,
      histograms, and either analysis of variance or Kruskal-Wallis tests to analyse
      the data. PRINCIPAL RESULTS: Mean CN of the vascular New Zealand flora is about
      twice that of Italy. For most orders, mean CN values for New Zealand are higher
      than those of the Italian flora and the differences are statistically
      significant. Further differences in CN variation among the orders and main clades
      that we studied, irrespective of geographical distinctions, are revealed. No
      correlation was found between chromosome and B-chromosome number. CONCLUSIONS:
      Mean CN of the whole New Zealand dataset is about twice that of the Italian
      flora. This suggests that extensive polyploidization played a major role in the
      evolution of the New Zealand vascular flora that is characterized by a rate of
      high endemism. Our results show that the hypothesis of a polyploid increase
      proportional to distance from the Equator cannot be applied to territories with
      the same latitudinal ranges but placed in different hemispheres. We suggest that
      bioclimatic gradients, rather than or in addition to latitudinal gradients, might
      account for a polyploidy increase. Our data also suggest that any adaptive role
      of B-chromosomes at geographic scale may be sought in their frequency rather than
      in their number.

PMID- 22476489
TI  - Pollen tube energetics: respiration, fermentation and the race to the ovule.
AB  - BACKGROUND: Pollen tubes grow by transferring chemical energy from stored
      cellular starch and newly assimilated sugars into ATP. This drives myriad
      processes essential for cell elongation, directly or through the creation of ion
      gradients. Respiration plays a central role in generating and regulating this
      energy flow and thus in the success of plant reproduction. Pollen tubes are
      easily grown in vitro and have become an excellent model for investigating the
      contributions of respiration to plant cellular growth and morphogenesis at the
      molecular, biochemical and physiological levels. SCOPE: In recent decades, pollen
      tube research has become increasingly focused on the molecular mechanisms
      involved in cellular processes. Yet, effective growth and development requires an
      intact, integrated set of cellular processes, all supplied with a constant flow
      of energy. Here we bring together information from the current and historical
      literature concerning respiration, fermentation and mitochondrial physiology in
      pollen tubes, and assess the significance of more recent molecular and genetic
      investigations in a physiological context. CONCLUSIONS: The rapid growth of the
      pollen tube down the style has led to the evolution of high rates of pollen tube
      respiration. Respiration rates in lily predict a total energy turnover of 40-50
      fmol ATP s(-1) per pollen grain. Within this context we examine the energetic
      requirements of cell wall synthesis, osmoregulation, actin dynamics and cyclosis.
      At present, we can only estimate the amount of energy required, because data from
      growing pollen tubes are not available. In addition to respiration, we discuss
      fermentation and mitochondrial localization. We argue that the molecular pathways
      need to be examined within the physiological context to understand better the
      mechanisms that control tip growth in pollen tubes.

PMID- 22476491
TI  - Isolated history of the coastal plant Lathyrus japonicus (Leguminosae) in Lake
      Biwa, an ancient freshwater lake.
AB  - BACKGROUND AND AIMS: Lake Biwa is one of the world's few ancient lakes. Formed ~4
      million years ago, the lake harbours many coastal species that commonly inhabit
      seashores. The beach pea Lathyrus japonicus is a typical coastal species of this
      freshwater lake, but its inland populations are faced with the threat of
      extinction. Here, we investigated the phylogeographical and population structures
      of both inland and coastal populations of L. japonicus. We also elucidated the
      historical isolation of the Lake Biwa population. METHODOLOGY: In total, 520
      individuals from 50 L. japonicus populations were sampled throughout the species
      distribution in Japan. Chloroplast haplotyping using intergenic spacers psbA-trnH
      and atpI-atpH was performed to investigate the phylogeographical structure as
      well as the genetic diversity of L. japonicus. Six nuclear microsatellite markers
      were also used to analyse the population structure. PRINCIPAL RESULTS: Population
      structure analyses of chloroplast DNA (cpDNA) and nuclear DNA (nDNA) identified
      inland and coastal groups. Based on the genetic differentiation, inland
      populations exhibited a single cpDNA haplotype and significantly lower values of
      H(S), AR and F(IS) than coastal populations. In addition to the presence of a
      bottleneck, the lack of gene flow among inland populations was supported by
      estimates of recent migration rates between subpopulations. CONCLUSIONS: Our data
      revealed that inland populations have been isolated in Lake Biwa as 'landlocked'
      populations since the predecessor lake was isolated from sea. This was also seen
      in a previous study of Calystegia soldanella. However, the high genetic
      differentiation, accompanied by a lack of gene flow among the Lake Biwa
      populations (according to the BAYESASS(+) analysis), contradicts the results with
      C. soldanella. We conclude that because of the presence of a bottleneck and low
      genetic diversity of the inland populations, self-sustaining population
      persistence may be difficult in the future. Conservation strategies must consider
      the genetic properties of such isolated populations.

PMID- 22476492
TI  - Salinity tolerance ecophysiology of Equisetum giganteum in South America: a study
      of 11 sites providing a natural gradient of salinity stress.
AB  - BACKGROUND AND AIMS: The basic set of adaptations necessary for salinity
      tolerance in vascular plants remains unknown. Although much has been published on
      salinity stress, almost all studies deal with spermatophytes. Studies of salinity
      tolerance in pteridophytes are relatively rare but hold promise for revealing the
      fundamental adaptations that all salt-tolerant vascular plants may share. The
      most basal pteridophytes to exhibit salinity tolerance are members of the genus
      Equisetum, including the giant horsetail, Equisetum giganteum, the only
      pteridophyte to occur in salinity-affected regions of the Atacama Desert valleys
      of northern Chile. Here it can constitute a significant vegetation component,
      forming dense stands of shoots >4 m high. METHODOLOGY: Physiological parameters
      (stomatal conductances; efficiency of photosystem II; sap osmotic potential) were
      measured in E. giganteum populations in northern Chile across a range of
      groundwater salinities at 11 sites. In addition, Na, K, electrical conductivity
      and total plant water potential were measured in the plants and groundwater from
      each site. PRINCIPAL RESULTS: Equisetum giganteum exhibits similar stomatal
      conductances and photochemical efficiencies of photosystem II across a wide range
      of groundwater salinities. It lowers cell sap osmotic potential with increasing
      salinity and produces positive root pressure, as evidenced by guttation, at the
      full range of salinities experienced in the Atacama Desert. Equisetum giganteum
      maintains low Na concentrations in its xylem fluid and cell sap when soil water
      Na is high. It also maintains high K/Na ratios in xylem fluid and cell sap when
      soil water has low K/Na ratios. CONCLUSIONS: Equisetum giganteum is well adapted
      to salinity stress. Efficient K uptake and Na exclusion are important adaptations
      and closely similar to those of the facultative halophyte fern Acrostichum
      aureum.

PMID- 22476493
TI  - Reductions in biomass accumulation, photosynthesis in situ and net carbon balance
      are the costs of protecting Vitis vinifera 'Semillon' grapevines from heat stress
      with shade covering.
AB  - BACKGROUND AND AIMS: Covering whole vines with shade cloth is used to protect the
      vines from heat stress, but may have costs on vine productivity through reduced
      light availability. Our aim was to assess the carbon balance of vines growing
      with and without shade to quantify the impact of the covering. METHODOLOGY: Whole
      vines were covered with 70 % shade cloth, and shoot leaf area and leaf, stem and
      bunch growth were followed over two growing seasons. Photosynthesis was measured
      in situ in all leaves along selected shoots over the growing season. A carbon
      balance was constructed from the difference in acquisition of carbon and the
      sequestration of carbon as biomass across the growing seasons. PRINCIPAL RESULTS:
      Shade covering had no initial impact on shoot growth but later reduced leaf
      growth and later still bunch growth. Stem growth was unaffected. Photosynthetic
      properties were characteristic of shade leaves, with lower rates and lower light
      saturation compared with well-exposed leaves. Overall, net photosynthesis was
      reduced by 40 % by the shade covering and was attributed to the reduced photon
      flux densities. From the carbon balance, vines were reliant on carbon reserves
      over 6 weeks after budbreak until current photosynthate increased sufficiently to
      supply the growth. Shade covering impacted most on biomass accumulation to leaves
      and bunches at the stage when the vines became autotrophic, consistent with the
      reduction in carbon acquisition. The markedly high carbon demand by bunches
      caused a mid-season negative carbon balance, implying that shoots had to draw
      further on reserves to supply the carbon. CONCLUSIONS: Shade covering over whole
      grapevines exacerbated the imbalance between the supply of and demand for carbon
      and greatly reduced vine biomass, especially reproductive allocation. Covering
      vines with shade cloth to protect the vines from heat events, therefore, had
      major costs in the carbon economy.

PMID- 22476494
TI  - A platform for efficient genotyping in Musa using microsatellite markers.
AB  - BACKGROUND AND AIMS: Bananas and plantains (Musa spp.) are one of the major fruit
      crops worldwide with acknowledged importance as a staple food for millions of
      people. The rich genetic diversity of this crop is, however, endangered by
      diseases, adverse environmental conditions and changed farming practices, and the
      need for its characterization and preservation is urgent. With the aim of
      providing a simple and robust approach for molecular characterization of Musa
      species, we developed an optimized genotyping platform using 19 published simple
      sequence repeat markers. METHODOLOGY: The genotyping system is based on 19
      microsatellite loci, which are scored using fluorescently labelled primers and
      high-throughput capillary electrophoresis separation with high resolution. This
      genotyping platform was tested and optimized on a set of 70 diploid and 38
      triploid banana accessions. PRINCIPAL RESULTS: The marker set used in this study
      provided enough polymorphism to discriminate between individual species,
      subspecies and subgroups of all accessions of Musa. Likewise, the capability of
      identifying duplicate samples was confirmed. Based on the results of a blind
      test, the genotyping system was confirmed to be suitable for characterization of
      unknown accessions. CONCLUSIONS: Here we report on the first complex and
      standardized platform for molecular characterization of Musa germplasm that is
      ready to use for the wider Musa research and breeding community. We believe that
      this genotyping system offers a versatile tool that can accommodate all possible
      requirements for characterizing Musa diversity, and is economical for samples
      ranging from one to many accessions.

PMID- 22476495
TI  - Phylogeny and divergence times inferred from rps16 sequence data analyses for
      Tricyrtis (Liliaceae), an endemic genus of north-east Asia.
AB  - BACKGROUND AND AIMS: Tricyrtis is a genus of monocots with attractive and
      sophisticated flower shapes and colours, endemic to north-east Asia. There are 18
      known species. The highly restricted geographical distribution of the genus is of
      great interest in terms of both abiotic (continental drift) and biotic (long
      distance dispersal) impacts on monocot plant speciation events and their timing,
      and of evolutionary patterns of diversification leading to the extant taxa. The
      aims of this study were to (i) predict the time of speciation (divergence) events
      at infraspecific levels of Tricyrtis, (ii) estimate the rate of evolution of the
      genus and (iii) provide information on an excellent plant model system in terms
      of studying loss of biodiversity or extinction of organisms in the dynamic earth
      environment. METHODOLOGY: To investigate the divergence time and evolution rate
      of Tricyrtis, Bayesian Markov chain Monte Carlo (MCMC) analyses were performed by
      calculating the mean branch lengths of evolutionary paths based on base
      substitution variations between rps16 intron nucleotide sequences from the 18
      known species. PRINCIPAL RESULTS: Based upon the relaxed molecular clock model
      test data, a Bayesian phylogenetic inference tree is presented, and the
      divergence times and rate of evolution of Tricyrtis were estimated. The analyses
      also suggest that evolution is occurring at the infraspecific level of the genus
      in a manner that is not strictly clock bound. CONCLUSIONS: Continental drift may
      have been the main speciation process giving rise to the current distribution of
      the taxa of Tricyrtis. The single-locus gene sequence data presented here are a
      significant step towards an improved future understanding of the molecular
      evolution of Tricyrtis via multi-locus evaluation.

PMID- 22476496
TI  - Coordinated changes in storage proteins during development and germination of
      elite seeds of Pongamia pinnata, a versatile biodiesel legume.
AB  - BACKGROUND AND AIMS: The oleaginous legume Pongamia pinnata is a rapidly growing
      and economically important tree. The seeds are used increasingly as feedstock for
      biodiesel production, with the protein-rich residue providing valuable supplement
      to farm animal diets. However, little is known about seed development and the
      characteristics of germination. We therefore studied morphological, protein and
      ultrastructural changes during seed maturation and germination using seeds from a
      tree selected for superior morphological and reproductive characters (candidate
      plus tree). METHODOLOGY: Phenology, sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE), and scanning and transmission electron microscopy
      were used to investigate seed development from 90 to 350 days after flowering
      (DAF), and germination and seedling development from 0 to 45 days after the start
      of imbibition (DAI) (Stages 0-VII). PRINCIPAL RESULTS: Seven distinct
      developmental stages were identified during seed development. Fresh weight,
      length, breadth and thickness increased from Stage I (90 DAF) to V (270 DAF) and
      decreased at Stages VI (315 DAF) and VII (350 DAF), when the seeds were fully
      ripe. Marked changes in total soluble protein content and SDS-PAGE profile were
      observed in vegetative and reproductive tissues and in the cotyledons of
      germinating seedlings. Polypeptide fragments of 150-14 kDa were observed during
      seed maturation and germination. In SDS-PAGE the expression of three main
      polypeptide bands (50, 18 and 14 kDa) increased from Stage I to Stage V and then
      almost became the same until Stage VII during seed maturation. During germination
      the expression of 50 kDa polypeptide decreased and that of 18 and 14 kDa
      increased from Stage 0 (ungerminated seed) to Stage VI (30 DAI), respectively;
      however, all three polypeptides (50, 18 and 14 kDa) completely disappeared at
      Stage VII (45 DAI). Ultrastructural changes during four stages of seed maturation
      (early immature, 90-135 DAF; late immature, 180-225 DAF; early mature, 225-270
      DAF; and late mature, 315-350 DAF) and three stages of germination and seedling
      development (early 10 DAI to late 45 DAI) localized marked gradients in protein
      storage reserves. CONCLUSIONS: Increasing the knowledge base for P. pinnata,
      especially for its seeds, is an essential prerequisite for rapid and successful
      exploitation of this promising energy and animal feed crop. Our findings
      contribute to this by establishing key developmental features of the seeds as
      they form and germinate.

PMID- 22476497
TI  - Evolutionary development of the plant and spore wall.
AB  - BACKGROUND AND AIMS: Many key innovations were required to enable plants to
      colonize terrestrial habitats successfully. One of these was the acquisition of a
      durable spore/pollen wall capable of withstanding the harsh desiccating and UV-B
      rich environment encountered on land. The spores of 'lower' spore-bearing plants
      and the pollen of 'higher' seed plants are homologous. In recent years,
      researchers have begun to investigate the molecular genetics of pollen wall
      development in angiosperms (including the model organism Arabidopsis thaliana).
      However, research into the molecular genetics of spore wall development in more
      basal plants has thus far been extremely limited. This review summarizes the
      literature on spore/pollen wall development, including the molecular genetics
      associated with pollen wall development in angiosperms, in a preliminary attempt
      to identify possible candidate genes involved in spore wall development in more
      basal plants. PRESENCE IN MOSS OF GENES INVOLVED IN POLLEN WALL DEVELOPMENT:
      Bioinformatic studies have suggested that genes implicated in pollen wall
      development in angiosperms are also present in moss and lycopsids, and may
      therefore be involved in spore wall development in basal plants. This suggests
      that the molecular genetics of spore/pollen development are highly conserved,
      despite the large morphological and functional differences between spores and
      pollen. FUTURE WORK: The use of high-throughput sequencing strategies and/or
      microarray experiments at an appropriate stage of 'lower' land plant sporogenesis
      will allow the identification of candidate genes likely to be involved in the
      development of the spore wall by way of comparison with those genes known to be
      involved in pollen wall development. Additionally, by conducting gene knock-out
      and gene swap experiments between 'lower' land plant species, such as the moss
      model species Physcomitrella patens, and the angiosperm model species arabidopsis
      it will be possible to test the role of these candidate genes.

PMID- 22476498
TI  - Dividing without centrioles: innovative plant microtubule organizing centres
      organize mitotic spindles in bryophytes, the earliest extant lineages of land
      plants.
AB  - BACKGROUND AND AIMS: As remnants of the earliest land plants, the bryophytes
      (liverworts, mosses and hornworts) are important in understanding microtubule
      organization in plant cells. Land plants have an anastral mitotic spindle that
      forms in the absence of centrosomes, and a cytokinetic apparatus comprised of a
      predictive preprophase band (PPB) before mitosis and a phragmoplast after
      mitosis. These microtubule arrays have no counterpart in animal cells and the
      nature of the plant microtubule organizing centre (MTOC) remained an enigma for
      many years until antibodies to gamma-tubulin, an essential component of the MTOC
      in all eukaryotes, became available for tracing the origin of microtubule arrays.
      METHODOLOGY: We used immunofluorescence techniques to colocalize gamma-tubulin,
      microtubules and chromosomes in mitotic cells of a representative liverwort, moss
      and hornwort to study the organization of microtubules during mitotic cell
      division. PRINCIPAL RESULTS: THE FUTURE DIVISION SITE IS MARKED BY A PPB IN ALL
      TAXA BUT THE MTOCS INITIALLY GENERATING THE HALF SPINDLES DIFFER: polar
      organizers in the liverwort, plastid MTOCs in the hornwort, and nuclear envelope
      associated MTOCs in the moss. By mid-prophase, the forming spindles become more
      similar as gamma-tubulin begins to spread around the polar regions of the nuclear
      envelope. CONCLUSIONS: Regardless of origin, mature metaphase spindles are
      identical and indistinguishable from the typical anastral spindle of higher
      plants with broad polar regions consisting of numerous subsets of converging
      microtubules. A curious phenomenon of plant spindles, true of bryophytes as well
      as higher plants, is the movement of gamma-tubulin into the metaphase spindle
      itself. The bipolar arrays of phragmoplast microtubules are organized by diffuse
      gamma-tubulin located at proximal surfaces of reforming nuclear envelopes.
      Phragmoplast development appears similar in the three taxa and to vascular plants
      as well.

PMID- 22476499
TI  - Conservation genetics of the rare Pyreneo-Cantabrian endemic Aster pyrenaeus
      (Asteraceae).
AB  - BACKGROUND AND AIMS: Aster pyrenaeus (Asteraceae) is an endangered species,
      endemic to the Pyrenees and Cantabrian Mountain ranges (Spain). For its long-term
      persistence, this taxon needs an appropriate conservation strategy to be
      implemented. In this context, we studied the genetic structure over the entire
      geographical range of the species and then inferred the genetic relationships
      between populations. METHODOLOGY: Molecular diversity was analysed for 290
      individuals from 12 populations in the Pyrenees and the Cantabrian Mountains
      using inter simple sequence repeats (ISSRs). Bayesian-based analysis was applied
      to examine population structure. PRINCIPAL RESULTS: Analysis of genetic
      similarity and diversity, based on 87 polymorphic ISSR markers, suggests that
      despite being small and isolated, populations have an intermediate genetic
      diversity level (P % = 52.8 %, H(E) = 0.21 +/- 0.01, genetic similarity between
      individuals = 49.6 %). Genetic variation was mainly found within populations (80
      84 %), independently of mountain ranges, whereas 16-18 % was found between
      populations and <5 % between mountain ranges. Analyses of molecular variance
      indicated that population differentiation was highly significant. However, no
      significant correlation was found between the genetic and geographical distances
      among populations (Rs = 0.359, P = 0.140). Geographical structure based on
      assignment tests identified five different gene pools that were independent of
      any particular structure in the landscape. CONCLUSIONS: The results suggest that
      population isolation is probably relatively recent, and that the outbreeding
      behaviour of the species maintains a high within-population genetic diversity. We
      assume that some long-distance dispersal, even among topographically remote
      populations, may be determinant for the pattern of genetic variation found in
      populations. Based on these findings, strategies are proposed for genetic
      conservation and management of the species.

PMID- 22476500
TI  - A perspective on underwater photosynthesis in submerged terrestrial wetland
      plants.
AB  - BACKGROUND AND AIMS: Wetland plants inhabit flood-prone areas and therefore can
      experience episodes of complete submergence. Submergence impedes exchange of O(2)
      and CO(2) between leaves and the environment, and light availability is also
      reduced. The present review examines limitations to underwater net photosynthesis
      (P(N)) by terrestrial (i.e. usually emergent) wetland plants, as compared with
      submerged aquatic plants, with focus on leaf traits for enhanced CO(2)
      acquisition. SCOPE: Floodwaters are variable in dissolved O(2), CO(2), light and
      temperature, and these parameters influence underwater P(N) and the growth and
      survival of submerged plants. Aquatic species possess morphological and
      anatomical leaf traits that reduce diffusion limitations to CO(2) uptake and thus
      aid P(N) under water. Many aquatic plants also have carbon-concentrating
      mechanisms to increase CO(2) at Rubisco. Terrestrial wetland plants generally
      lack the numerous beneficial leaf traits possessed by aquatic plants, so
      submergence markedly reduces P(N). Some terrestrial species, however, produce new
      leaves with a thinner cuticle and higher specific leaf area, whereas others have
      leaves with hydrophobic surfaces so that gas films are retained when submerged;
      both improve CO(2) entry. CONCLUSIONS: Submergence inhibits P(N) by terrestrial
      wetland plants, but less so in species that produce new leaves under water or in
      those with leaf gas films. Leaves with a thinner cuticle, or those with gas
      films, have improved gas diffusion with floodwaters, so that underwater P(N) is
      enhanced. Underwater P(N) provides sugars and O(2) to submerged plants.
      Floodwaters often contain dissolved CO(2) above levels in equilibrium with air,
      enabling at least some P(N) by terrestrial species when submerged, although rates
      remain well below those in air.

PMID- 22476501
TI  - Petiole hyponasty: an ethylene-driven, adaptive response to changes in the
      environment.
AB  - BACKGROUND: Many plant species can actively reorient their organs in response to
      dynamic environmental conditions. Organ movement can be an integral part of plant
      development or can occur in response to unfavourable external circumstances.
      These active reactions take place with or without a directional stimulus and can
      be driven either by changes in turgor pressure or by asymmetric growth. Petiole
      hyponasty is upward movement driven by a higher rate of cell expansion on the
      lower (abaxial) compared with the upper (adaxial) side. Hyponasty is common among
      rosette species facing environmental stresses such as flooding, proximity of
      neighbours or elevated ambient temperature. The complex regulatory mechanism of
      hyponasty involves activation of pathways at molecular and developmental levels,
      with ethylene playing a crucial role. SCOPE: We present current knowledge on the
      mechanisms that promote hyponasty in the context of other organ movements,
      including tropic and nastic reactions together with circumnutation. We describe
      major environmental cues resulting in hyponasty and briefly discuss their
      perception and signal transduction. Since ethylene is a central agent triggering
      hyponasty, we focus on ethylene in controlling different stages during plant
      development and summarize current knowledge on the relationship between ethylene
      and cell growth.

PMID- 22476503
TI  - In-vitro maturation of human oocytes: before or after vitrification?
AB  - PURPOSE: This study aims to determine if in-vitro maturation (IVM) of human
      immature oocytes should be performed before or after vitrification. METHODS: A
      total of 184 immature oocytes were randomly divided into two different groups:
      100 were vitrified at metaphase II (MII) stage 24 h-48 h after IVM (group 1) and
      84 were immediately vitrified at germinal vesicle (GV) or metaphase I (MI) stages
      and in vitro matured after warming (group 2). RESULTS: Survival rate after
      warming was similar in both groups (86.9% versus 84.5%). However, oocyte
      maturation rate per collected oocyte was significantly higher for oocytes matured
      before vitrification (group 1, 46%) than for oocytes vitrified before IVM (group
      2, 23.8%) (p < 0.01). Consequently, the number of MII oocytes inseminated per
      oocyte collected was significantly higher for group 1 (40%) than for group 2
      (23.8%) (p < 0.05). CONCLUSION: IVM procedure is more efficient when it is
      performed before oocyte vitrification.

PMID- 22476502
TI  - Recommendations for measurement of tumour vascularity with positron emission
      tomography in early phase clinical trials.
AB  - The evaluation of drug pharmacodynamics and early tumour response are integral to
      current clinical trials of novel cancer therapeutics to explain or predict long
      term clinical benefit or to confirm dose selection. Tumour vascularity assessment
      by positron emission tomography could be viewed as a generic pharmacodynamic
      endpoint or tool for monitoring response to treatment. This review discusses
      methods for semi-quantitative and quantitative assessment of tumour vascularity.
      The radioligands and radiotracers range from direct physiological functional
      tracers like [(15)O]-water to macromolecular probes targeting integrin receptors
      expressed on neovasculature. Finally we make recommendations on ways to
      incorporate such measurements of tumour vascularity into early clinical trials of
      novel therapeutics. Key Points * [ ( 15 ) O]-water is the gold standard for blood
      flow/tissue perfusion with PET * In some instances dynamic [ ( 18 ) F]-FDG uptake
      may be used to estimate perfusion * Radiopharmaceuticals that target integrins
      are now being evaluated for measuring tumour vascularity.

PMID- 22476504
TI  - A novel chromosomal translocation and heteromorphism in a female with recurrent
      pregnancy loss--a case study.
AB  - PURPOSE: To evaluate the clinical, biochemical and cytogenetic analyses of a
      couple with reproductive failure. METHODS: A couple with a history of recurrent
      pregnancy loss was referred to the Institute of Genetics for cytogenetic
      evaluation. Chromosomal analysis of the phenotypically normal parents was done to
      ascertain the role of chromosomal abnormalities and offer appropriate genetic
      counseling. Further, advanced karyotype analysis by spectral karyotyping was also
      carried out in the couple and parents of the female partner. RESULTS: Clinical
      and hormonal profile of the couple revealed normal phenotypes. The ultrasound
      scan of the female showed normal uterus and ovaries. Chromosomal analysis of the
      couple revealed a normal 46, XY karyotype in the male spouse, and a unique
      balanced reciprocal translocation 46, XX, t(12;13) (q13;q33) + 15pstk+
      chromosomal constitution in the female partner. Cytogenetic analysis of her
      parents revealed a similar translocation between chromosomes 12 and 13 in the
      father and 15pstk+ in the mother. Further, corroboration of the chromosome
      abnormalities was carried out by spectral karyotyping. CONCLUSION: A unique and
      novel familial transmission of paternally derived balanced reciprocal
      translocation and maternally derived heteromorphism in a female with the history
      of recurrent pregnancy loss was reported as an original investigation.

PMID- 22476505
TI  - Female Lincoln's sparrows modulate their behavior in response to variation in
      male song quality.
AB  - Sexually reproducing organisms should mate with the highest quality individuals
      that they can. When female songbirds choose a mate, they are thought to use
      several aspects of male song that reflect his quality. Under resource-limited
      environmental conditions, male Lincoln's sparrows (Melospiza lincolnii) vary
      among one another in several aspects of song quality, including song length, song
      complexity, and trill performance. In a 2-pronged approach, we tested whether
      variation in song quality of male Lincoln's sparrows influences the behavior of
      females that are in a reproductive-like state. Over two trials, we exposed
      females to songs from the high and low ends of the distribution of naturally
      occurring song quality variation and found a higher level of behavioral activity
      in females exposed to high-quality songs, especially when they had first been
      exposed to low-quality songs. We also examined female phonotaxis toward
      antiphonally played songs with experimentally elevated and reduced trill
      performance and found that females moved preferentially toward the songs with
      elevated trill performance. Contrary to most studies investigating the behavioral
      responses of wild, female songbirds to variation in male song, we obtained our
      results without administering exogenous estradiol, which can artificially perturb
      the female's physiology. Our results demonstrate that the behavior of female
      Lincoln's sparrows is modulated by the quality of male songs to which they are
      exposed and that trill performance plays a significant role in this behavioral
      modulation. Furthermore, as the order of song quality presentation matters, it
      appears that recent song experience also influences female behavior.

PMID- 22476506
TI  - Serial transverse enteroplasty (STEP): intermediate outcomes in children with
      short bowel syndrome.
AB  - Short bowel syndrome is the most common cause of intestinal failure in children.
      The treatment is based on a multidisciplinary approach involving pediatricians,
      pediatric surgeons, and nutritionists. Surgical procedures for intestinal
      lengthening may be decisive, having been revalued after the recent description of
      serial transverse enteroplasty (STEP). We reviewed the patients who underwent the
      STEP operation for short bowel syndrome in our hospital in order to evaluate
      medium-term outcome. Between April 2006 and December 2008, three children were
      submitted to STEP without postoperative complications directly related to the
      procedure. In two cases the autonomy for oral/enteric feeding was obtained within
      3 and 7 months after surgery with sustained growth, persisting at 5 years of
      follow-up after STEP. One child remained dependent of parenteral nutrition and
      was submitted to intestinal transplantation 30 months after STEP. However, since
      STEP until transplantation, it was possible to increase enteric volume and
      decrease intestinal dilation and the frequency of occlusive episodes. STEP is an
      effective and safe technique for intestinal lengthening that may allow increased
      tolerance to oral/enteric feeding or at least alleviate some complications of
      short bowel syndrome.

PMID- 22476507
TI  - Kikuchi-Fujimoto disease following vaccination against human papilloma virus
      infection and Japanese encephalitis.
AB  - Kikuchi-Fujimoto disease (KFD) is a benign and self-limited syndrome,
      characterized by regional lymphadenopathy and fever. Although the pathogenesis of
      KFD remains unclear, infectious agents, autoimmune causes, and physicochemical
      factors have been suggested as triggers. However, KFD following vaccination has
      never been reported. We present a 14-year-old girl who suffered from fever and
      cervical lymph node swelling following simultaneous administration of human
      papilloma virus vaccine and Japanese encephalitis virus vaccine. The patient was
      diagnosed with KFD based on the histopathologic findings of a lymph node biopsy,
      and her fever and swelling resolved with oral corticosteroid therapy. Although
      the exact pathogenesis of the development of KFD following immunization remains
      unknown, this should be added to the list of potential triggers or factors
      associated with the development of KFD.

PMID- 22476508
TI  - Selection and characterization of aerosol particle size using a bessel beam
      optical trap for single particle analysis.
AB  - Bessel beams were used to create a counter-propagating optical trap for capturing
      and manipulating aerosol particles. Aerosol droplets were characterized through
      measurement of the elastic scattered light at three wavelengths; the trapping
      wavelength of 532 nm was used in conjunction with two probe beams at 405 nm and
      633 nm to reduce the uncertainty in estimating droplet radii of 1 MUm or less.
      Control of the aerosol size distribution sampled by the counter-propagating trap
      was demonstrated by varying the trapping beam core diameters and intensities.
      Smaller droplet sizes were preferentially selected with a 1.7 MUm core diameter
      compared to cores of 2.7 MUm and 4.5 MUm. Further, an increase in core intensity
      was shown to broaden the range in droplet sizes that were optically trapped. The
      possibility of using such an approach to isolate and analyze the properties of
      single accumulation mode aerosol particles is discussed. 

PMID- 22476509
TI  - [Neurotheology: neurobiological models of religious experience].
AB  - Religions are evolutionary selected social and cultural phenomena. They represent
      today belief and normative systems on which the main parts of our culture are
      based. For a long time religions have been seen as mainly originating from a
      spectrum of religious experiences. These include a broad spectrum of experiences
      and are astonishingly widespread in the population. The most consistent and
      transculturally uniform religious experiences are the mystical experiences. Only
      these (and the prayer experience) have factually been researched in detail
      neurobiologically. This article presents a review of empirical results and
      hypothetical approaches to explain mystical religious experiences
      neurobiologically. Some of the explanatory hypotheses possess logical evidence,
      some are even supported by neurobiological studies, but all of them have their
      pitfalls and are at best partially consistent. One important insight from the
      evidence reviewed here is that there may be a whole array of different
      neurophysiological conditions which may result in the same core religious
      mystical experiences.

PMID- 22476510
TI  - [Internet presence of psychiatrists in private practice. Status, chances and
      legal framework].
AB  - BACKGROUND: Physicians increasingly use home pages to call attention to their
      practice. Based on predefined criteria, this study examines the web presence of
      psychiatrists and medical psychotherapists in private practice. METHODS: All
      registered psychiatrists and psychotherapists of six northern German states were
      examined in May 2010 with regards to existence and quality of their web presence.
      Homepages were evaluated by means of a standardized criteria catalogue with 42
      items. Statistical analysis comprised descriptive and analytic approaches (ANOVA,
      linear models). RESULTS: The analysis included 956 physicians, 168 of whom
      (17.6%) had a web presence. More physicians in city states had a web presence as
      compared to those in states with larger territories. However, there was no
      difference between eastern and western states. Male as compared to female
      physicians more often possessed an Internet presence. The average score was 19
      (+/- 5.2) out of 42 items, with practices with more than one physician scoring
      higher than single physician practices. Websites often contained general
      information about the practice, medical services and diseases, and rarely online
      services, professional information about the physician, access for disabled,
      emergency services and holiday substitution. Legal requirements were not
      sufficiently considered by more than half of the physicians. CONCLUSION: Only a
      smaller number of psychiatrists and psychotherapists in private practice make use
      of their own web presence. The quality of information varies. The criteria
      catalogue used in this study may offer a guideline for development of a good
      quality Internet presence. A consensus Internet guideline with participation of
      physician chambers and medical societies would be of use to establish quality
      standards.

PMID- 22476511
TI  - [Substance use associated disorders: frequency in patients with schizophrenic and
      affective psychoses].
AB  - BACKGROUND: Alcohol and substance use disorders (ASUD) are considered to be among
      the most frequent comorbidities in schizophrenic and affective psychoses and have
      a significant negative influence on their course and prognosis. In the present
      study patients with diagnosis from the ICD-10 category F2 or F3 were examined
      regarding a substance use disorder in a multicentre cross-section evaluation at
      nine psychiatric hospitals in Baden-Wurttemberg. The aim of this study is to
      discuss the current research on substance use disorders and psychosis comorbidity
      regarding the theoretical models by means of collected data. METHODS: The
      examination of 50 consecutive admissions per centre is based on a shortened
      version of the European Severity Index (Europ ASI). An initial urine drug
      screening was carried out with all patients after admission. Statistical
      assessment was based on percentage distributions, mean values, standard
      deviations and suitable correlation analysis. RESULTS: The representative sample
      included 448 patients. A proportion of 169 patients (37.7%) had a dual diagnosis
      F2 and F1 and a proportion of 144 patients (32.1%) had a dual diagnosis F3 and
      F1; 64 patients (14.3%) had an F2 diagnosis and 71 patients (15.8%) had an F3
      diagnosis without ASUD. Apart from lifetime use of alcohol (n = 268) and tobacco
      (n = 325) hypnotics/tranquilizers (n = 214), cannabis (n = 156), opioids (n =
      71), stimulants (n = 96) and hallucinogens (n = 36) were consumed. The most
      frequent combination and long-term intake consisted of tobacco, alcohol,
      hypnotics/tranquilizer, cannabis and psychostimulants especially in men with
      schizophrenic disorders. Regarding motivation before first substance use general
      psychological adjustment disorders (51%), peer impact (42%) and unspecific
      affective symptoms were predominant. CONCLUSIONS: Altogether the present study
      clearly demonstrates that patients suffering from schizophrenia, affective
      disorders and ASUD have significantly higher rates of more severe substance use
      disorders in their psychosocial environment and more suicidal behaviour than
      patients without substance misuse. The high rate in the cross-sectional
      prevalence of tobacco, alcohol, cannabis and psychostimulant use calls for more
      effective drug prevention.

PMID- 22476512
TI  - [CLIPPERS: an increasingly diagnosed syndrome].

PMID- 22476513
TI  - [The experience of being admitted to a psychiatric clinic: part 2: comparative
      analyses of patient and hospital characteristics].
AB  - BACKGROUND: The purpose of this study was to investigate associations of
      patient's scores in the newly constructed questionnaire on patients' psychiatric
      admission experiences (QAE-P) and individual, institutional, and situational
      factors. PATIENTS AND METHODS: Data of 708 patients and 6 participating hospitals
      were analyzed. Patient characteristics between clinics were compared and
      univariate as well as multivariate analyses were applied to examine associations
      of QAE-P total score and individual as well as institutional variables (t tests,
      univariate and multivariate analyses of variance, correlation analyses, and
      effect sizes of significant associations). RESULTS: There was little variance of
      patient characteristics between hospitals. Multiple univariate associations with
      small to medium effect sizes were found between total QAE-P scores and
      demographic and clinical variables of the patients, institutional variables, and
      (non-independent) situational views of the patients. After multivariate analyses
      were applied, these associations remained significant for gender, age, diagnosis,
      the personal decision to be admitted, and for previous planning of admission with
      the outpatient doctor. The hospital variables shown to be associated with total
      QAE-P scores were open versus closed ward, disorder-specific organization of the
      ward, and the number of other patients being treated under the German Mental
      Health Act. CONCLUSION: Principally the QAE-P seems to be a suitable instrument
      of quality management. A number of factors were identified that show associations
      with the subjective evaluation of admission as reported by the patients. Some of
      these variables are within the control of the clinical management.

PMID- 22476514
TI  - Characteristics of late-onset myasthenia gravis.
AB  - An increasing incidence of myasthenia gravis (MG) has been reported in the
      elderly, but the full clinical ramifications of late-onset myasthenia gravis
      (LOMG) remain unclear. We describe the clinical features of our cohort of
      patients with MG with an emphasis on an onset after the age of 50. This was a
      retrospective analysis of medical records of a cohort of patients followed in two
      tertiary neuromuscular clinics and comparison of early onset MG (EOMG) versus
      LOMG. There were 174 patients with a mean age of onset of 55.2 +/- 19.1 years,
      and 44 % were women. Late onset of myasthenia gravis after age 50 was reported in
      114 patients (66 %). Anti-AChR antibody titers were elevated in 78 % of patients
      (65 % with EOMG vs. 85 % with LOMG; p = 0.003), and frequency of elevated titers
      of anti-MuSK antibodies was similar in both groups (present in 38 % of all tested
      seronegative patients). Myasthenic crisis was equally common in generalized EOMG
      and LOMG (13 %). Ocular MG was more common in LOMG compared to EOMG (40 vs. 18 %,
      p = 0.021). Diabetes was more prevalent with LOMG (27 vs. 5 %; p = 0.0002).
      Overlapping clinical features of EOMG and LOMG are consistent with a continuous
      clinical spectrum of a single condition, with more frequent occurrence of
      seropositive and ocular MG with a late onset. A higher burden of comorbidities,
      such as diabetes mellitus, may warrant a modified approach to treatment of
      myasthenia in LOMG. However, overall disease severity may not be higher with
      aging. These observations have implications for design of MG clinical trials and
      outcomes studies.

PMID- 22476515
TI  - Evaluating home range techniques: use of Global Positioning System (GPS) collar
      data from chacma baboons.
AB  - Global Positioning System (GPS) collars have revolutionized the field of spatial
      ecology, but to date, few primate studies have used them. We fitted a free
      ranging, semi-habituated, juvenile male chacma baboon (Papio hamadryas ursinus)
      with an automatic self-releasing GPS collar and tracked his movements for 359
      days. The collar captured 4254 fixes out of 5719 programmed opportunities, a 74.4
      % acquisition rate, suggesting that the collar effectively tracked this baboon in
      a variety of habitat types. Of the data points captured, 73.7 % were three
      dimensional fixes, and of these fixes, 66.9 % were highly accurate, having a
      dilution of precision of less than four. We calculated home range using three
      protocols with three estimation methods: minimum convex polygon, fixed kernel
      density estimation (KDE), and fixed r local convex hull. Using all data points
      and the 95 % contour, these methods created home range estimations ranging from
      10.8 to 23.1 km(2) for this baboon troop. Our results indicate that the KDE
      output using all data locations most accurately represented our data set, as it
      created a continuous home range boundary that excluded unused areas and outlying,
      potentially exploratory data points while including all seven sleeping sites and
      a movement corridor. However, home range estimations generated from KDE varied
      from 15.4 to 18.8 km(2) depending on the smoothing parameter used. Our results
      demonstrated that the ad hoc smoothing parameter selection technique was a better
      method for our data set than either the least squares cross-validation or biased
      cross-validation techniques. Our results demonstrate the need for primatologists
      to develop a standardized reporting method which documents the tool, screening
      protocol, and smoothing parameter used in the creation of home range estimations
      in order to make comparisons that are meaningful.

PMID- 22476516
TI  - A new skill for treating unclassified thumb polydactyly: ablation via a
      periosteal incision.
AB  - BACKGROUND: Thumb polydactyly is a common congenital abnormality of the hand.
      Surgical treatment includes reduction and reconstruction. A new type of thumb
      polydactyly and the achieved treatment are reported. METHODS: A 4-year-old boy
      with thumb polydactyly is reported. The duplicated two thumbs had one complete
      metacarpal and a separated triphalangeal phalanx. The ulna thumb was removed via
      periosteal incision, and a whole complex tissue sleeve was used to repair the
      ulna part of the joint capsule. RESULTS: The postoperative aesthetic and
      functional results were satisfactory. CONCLUSIONS: A new type of thumb
      polydactyly that cannot be matched with the classification of either Wassel or
      Wood is described. The thumb polydactyly was treated by ablation via periosteal
      incision and ulna metacarpophalangeal joint capsule reconstruction. Three
      dimensional computed tomography could be a good way to examine the area
      preoperatively. LEVEL OF EVIDENCE V: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors at www.springer.com/00266.

PMID- 22476517
TI  - The impact of triamcinolone acetonide in early breast capsule formation in a
      rabbit model.
AB  - BACKGROUND: The etiology and clinical treatment of capsular contracture remain
      unresolved as the causes may be multifactorial. Triamcinolone acetonide applied
      in the pocket during surgery was reported to be ineffective in prevention of
      capsular contracture. However, if injected 4-6 weeks after surgery or as a
      treatment for capsular contracture, decreased applanation tonometry measurements
      and pain were observed. It was assumed that intraoperative application of
      triamcinolone was not effective because its effect does not last long enough.
      However, betadine, antibiotics, and fibrin were found to be effective in
      preventing capsular contracture with intraoperative applications and are more
      effective in the early phases of wound healing than in later stages. The role of
      triamcinolone acetonide in capsule formation is unknown. The purpose of this
      study was to determine if triamcinolone acetonide modulates breast capsule
      formation or capsular contracture in the early phases of wound healing in a
      rabbit model. METHODS: Rabbits (n=19) were implanted with one tissue expander and
      two breast implants and were killed at 4 weeks. Implant pocket groups were (1)
      Control (n=10) and (2) Triamcinolone (n=9). Pressure/volume curves and
      histological, immunological, and microbiological evaluations were performed.
      Operating room air samples and contact skin samples were collected for
      microbiological evaluation. RESULTS: In the triamcinolone group, a decreased
      capsular thickness, mild and mononuclear inflammation, and negative or mild
      angiogenesis were observed. There were no significant differences in
      intracapsular pressure, fusiform cell density, connective tissue, organization of
      collagen fibers, and microbiological results between the groups. There was no
      significant difference in the dialysate levels of IL-8 and TNF-alpha, but
      correlation between IL-8 and TNF-alpha was observed. CONCLUSION: Triamcinolone
      acetonide during breast implantation influences early capsule formation and may
      reduce capsular contracture. LEVEL OF EVIDENCE III: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors at www.springer.com/00266.

PMID- 22476518
TI  - Correlates of same-sex attractions and behaviors among self-identified
      heterosexual university students.
AB  - Few studies have focused on intragroup variations in sexual orientation and fewer
      on self-identified heterosexuals with same-sex attractions, fantasies, and/or
      behaviors. Self-identified heterosexual students at a large public midwestern
      university (N = 263) completed measures of sexuality and gender, attitudes toward
      lesbian, gay, and bisexual (LGB) people, religious and political beliefs,
      emotional well-being, and demographics. The sample included 82 individuals (31%;
      labeled "H+") who endorsed same-sex attraction, fantasy, and/or behavior and 181
      (69%; labeled "H") who did not. Women were more likely to be categorized as H+
      than men. H+ participants had more positive attitudes toward lesbians and gay and
      bisexual men and reported more support for LGB-positive public policies than did
      H participants. H+ participants reported less literalistic beliefs about
      religious scripture than did H participants. H and H+ groups did not differ
      significantly on measures of emotional well-being. Results were discussed in the
      context of recent literature arguing for a more nuanced and gender-differentiated
      approach toward assessing sexual orientation, as well as literature on the
      flexibility of sexual orientation and on heterosexual identity development.

PMID- 22476519
TI  - On the relationship among social anxiety, intimacy, sexual communication, and
      sexual satisfaction in young couples.
AB  - This study was conducted to better understand why socially anxious individuals
      experience less sexual satisfaction in their intimate partnerships than
      nonanxious individuals, a relationship that has been well documented in previous
      research. Effective communication between partners is an important predictor of
      relationship satisfaction. Sexual communication, an important aspect of
      communication between romantic partners, is especially sensitive for couples
      given the vulnerability inherent in being open about sexual issues. Because
      socially anxious individuals characteristically report fear of evaluation or
      scrutiny by others, we hypothesized that the process of building intimacy by
      sharing personal information about oneself with one's partner, including when
      this information relates to one's sexuality and/or the sexual domain of the
      relationship, would be particularly difficult for socially anxious individuals.
      The present study examined fear of intimacy and sexual communication as potential
      mediators of the relationship between higher social anxiety and lower sexual
      satisfaction. Self-report data were collected from 115 undergraduate students and
      their partners in monogamous, heterosexual, committed relationships of at least 3
      months duration. Multilevel path modeling revealed that higher social anxiety
      predicted higher fear of intimacy, which predicted lower satisfaction with open
      sexual communication, which, in turn, predicted lower sexual satisfaction.
      Additionally, there was evidence of mediation as there were significant indirect
      effects of the antecedent variables on sexual satisfaction. The path model had
      excellent fit. Implications for social anxiety, intimate relationships, and
      couples therapy are discussed.

PMID- 22476520
TI  - White matter volumes in pedophiles, hebephiles, and teleiophiles.

PMID- 22476521
TI  - Synthesis of U(IV) imidos from Tp*2U(CH2Ph) (Tp* = hydrotris(3,5
      dimethylpyrazolyl)borate) by extrusion of bibenzyl.
AB  - Addition of organic azides, N(3)R (R = 2,4,6-trimethylphenyl (Mes), phenyl (Ph),
      1-adamantyl (Ad)), to a solution of the uranium(III) alkyl complex,
      Tp*(2)U(CH(2)Ph) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) (1), results in
      the formation of a family of uranium(iv) imido derivatives, Tp*(2)U(NR) (2-R).
      Notably, these complexes were synthesized in high yields by coupling of the
      benzyl groups to form bibenzyl. The uranium(IV) imido derivatives, 2-Mes, 2-Ph,
      and 2-Ad, were all characterized by both (1)H NMR and IR spectroscopy, and 2-Mes
      and 2-Ad were also characterized by X-ray crystallography. In the molecular
      structure of 2-Mes, typical kappa(3)-coordination of the Tp* ligands was
      observed; however in the case of 2-Ad, one pyrazole ring of a Tp* ligand has
      rotated away from the metal centre, forcing a kappa(2)-coordination of the
      pyrazoles. This results in a uranium-hydrogen interaction with the Tp* B-H.
      Treating these imido complexes with para-tolualdehyde results in multiple bond
      metathesis, forming the terminal uranium(IV) oxo complex, Tp*(2)U(O), and the
      corresponding imine.

PMID- 22476522
TI  - Nutrition and degeneration of articular cartilage.
AB  - PURPOSE: To determine the importance of synovial fluid (SF) or subchondral bone
      marrow (BM) as nutrition sources in cartilage degeneration. METHODS: Ninety-five
      month-old male rabbits were randomly divided into 5 groups according to sources
      of nutrition: SFBM-both; BM-only; SF-only; None-SFBM; and Free plug
      (unrestricted). Nutrition to 4-mm-diameter cylindrical osteochondral plugs
      created on the trochlea of the distal femurs was obstructed by Polyvinyl Chloride
      (PVC) cap. Cartilage changes were assessed after 4, 8, and 12 weeks by histology,
      immunohistochemistry, and real-time PCR. RESULTS: Cartilage in the BM-only group
      suffered the greatest damage, followed by the None-SFBM and SF-only groups.
      Apoptosis was increased in the BM-only and None-SFBM groups compared with others.
      Cartilage was significantly thinner at all time points in the BM-only and None
      SFBM groups when compared with SFBM-both and Free plug, whereas in the SF-only
      group, this difference occurred after 8 weeks. Compared with SFBM-both and Free
      plug, expression of collagen II and aggrecan mRNAs in all groups was decreased
      but MMP-3 increased, respectively. CONCLUSION: Our data indicate that SF-derived
      nutrition is the dominant source of sustenance for adult cartilage structure and
      function. Cartilage damage is observed when the only nutrition source is the BM.

PMID- 22476523
TI  - Specific injuries induced by the practice of trampoline, tumbling and acrobatic
      gymnastics.
AB  - PURPOSE: The recreational and competitive practice of acrobatic sports, that is,
      trampoline, tumbling and acrobatic gymnastics (ACRO), is growing rapidly around
      the world. Many studies described the injuries affecting young artistic gymnasts,
      but only few concerned acrobatic sports. METHODS: During a 5-year period, 357
      traumatic events were collected in young acrobats practicing trampoline, tumbling
      or ACRO. Accident characteristics, level of expertise and training, injury
      location (upper limb, spine and lower limb), type of tissue injured (bone,
      cartilage, muscle, ligament and tendon) and provoking factors
      (intrinsic/behavioural and extrinsic) were investigated. RESULTS: Acrobats of
      national and international levels were mostly injured. Injuries occurring in
      acrobatic sports concerned predominantly the lower limbs and concerned in this
      body part mainly damages to ligaments. Forearm and knee injuries were
      preferentially related to trampoline. Ankle injuries were preferentially related
      to tumbling. Wrist injuries were preferentially related to ACRO. Upper limb bone
      damage and upper limb tendon damage were preferentially related to trampoline and
      ACRO, respectively. Intrinsic/behavioural factors were the main injury
      determinant in the three acrobatic sports. CONCLUSIONS: The main injuries in
      acrobatic sports (i.e. lower limbs) are similar to those observed in artistic
      gymnastics. Specific injuries may result from falls and incomplete and/or
      erroneous figure's landing and may also depend to the type of the landing
      surface. LEVEL OF EVIDENCE: II.

PMID- 22476524
TI  - Femoro-tibial kinematics after TKA in fixed- and mobile-bearing knees in the
      sagittal plane.
AB  - PURPOSE: Lack of the anterior cruciate ligament in total knee arthroplasty
      results in paradoxical movement of the femur as opposed to the tibia under deep
      flexion. Total knee arthroplasty with mobile-bearing inlays has been developed to
      provide increased physiological movement of the knee joint and to reduce
      polyethylene abrasion. The aim of this study was to perform an in vitro analysis
      of the kinematic movement in the sagittal plane in order to show differences
      between fixed- and mobile-bearing TKA in comparison with the natural knee joint.
      METHODS: Seven knee joints of human cadaver material were used in a laboratory
      experiment. Fixed- and mobile-bearing inlays were tested in sequences under
      isokinetic extension in so-called kinemator for knee joints, which can simulate
      muscular traction power by the use of hydraulic cylinders, which crossover the
      knee joint. As a target parameter, the a.p. translation of the tibio-femoral
      relative movement was measured in the sagittal plane under ultrasound (Zebris)
      control. RESULTS: The results show a reduced tibial a.p. translation in relation
      to the femur in the bearing group compared to the natural joint. In the Z-axis,
      between 110 degrees  and 50 degrees  of flexion, linear movement decreases
      towards caudal movement under extension. Admittedly, the study did not show
      differences in the movement pattern between "mobile-bearing" and "fixed-bearing"
      prostheses. CONCLUSION: Results of this study cannot prove functional advantages
      of mobile-bearing prostheses for the knee joint kinematic after TKA. Both types
      of prostheses show typical kinematics of an anterior instability, hence they were
      incapable of performing physiological movement.

PMID- 22476525
TI  - Variability of the location of the tibial tubercle affects the rotational
      alignment of the tibial component in kinematically aligned total knee
      arthroplasty.
AB  - PURPOSE: Our experience with computer plans of kinematically aligned total knee
      arthroplasty showed that the anteroposterior (AP) axis of the tibial component
      when viewed in an axial plane did not consistently intersect either the medial
      border or the medial 1/3 of the tibial tubercle. The purposes were (1) to
      determine the variability in the mediolateral location of the tibial tubercle
      with respect to the medial tibia on the magnetic resonance image (MRI) of the
      knee and (2) to determine whether the AP axis of the kinematically aligned tibial
      component intersects either the medial border or the medial 1/3 of the tibial
      tubercle. METHODS: One hundred and fifteen knees in 111 consecutive subjects
      treated with total knee arthroplasty were studied. The mediolateral location of
      the tibial tubercle was measured from a magnetic resonance image (MRI) of the
      knee. The distances between the AP axis of the tibial component and the medial
      border of the tibial tubercle and between the AP axis and the medial 1/3 of the
      tibial tubercle were measured from a computer plan of the reconstructed knee.
      RESULTS: On the MRI, the medial border of the tibial tubercle varied 15 mm from
      the medial border of the tibia. On the computer plan, the AP axis of the tibial
      component in an axial view of the tibia did not intersect either the medial
      border (p < 0.0001) or the medial 1/3 of the tibial tubercle (p < 0.0001). In 70
      and 86 % of knees, the mediolateral distance of the AP axis of the tibial
      component was 2 mm or greater from the medial border of the tibial tubercle and
      the medial 1/3 of the tibial tubercle, respectively, which causes a clinically
      meaningful error in rotation of 5 degrees  or more. CONCLUSIONS: Because the
      mediolateral location of the tibial tubercle varies, the medial border and medial
      1/3 of the tibial tubercle are not reliable landmarks when the goal is to
      kinematically align the rotation of the tibial component on the tibia. LEVEL OF
      EVIDENCE: IV.

PMID- 22476526
TI  - Transtibial versus low anteromedial portal drilling for anterior cruciate
      ligament reconstruction: a radiographic study of femoral tunnel position.
AB  - PURPOSE: The purpose of this study is to compare femoral tunnel positions after
      ACL reconstruction by the transtibial (TT) approach versus the low anteromedial
      approach using radiographs from a single surgeon. METHODS: The standard
      postoperative knee radiographs of 50 patients with an ACL reconstruction were
      studied. Two groups were determined according to the technique used. The low
      anteromedial portal group and the transtibial portal group. The femoral bone
      tunnel was identified radiographically, and its position determined in the
      lateral and A-P view. Coronal and sagittal obliquity of the tunnel was measured
      and compared among both groups. RESULTS: In the sagittal plane, femoral bone
      tunnels averaged 54 degrees  +/- 6 degrees  for the TT technique and 59 degrees 
      +/- 12 degrees  (p = 0.07) for the low anteromedial portal technique. In the
      coronal plane, the bone tunnels drilled through the low anteromedial portal
      showed a significantly more oblique femoral tunnel position (50 degrees  +/- 6
      degrees ) compared to TT drilling (58 degrees  +/- 9 degrees ), p <= 0.05.
      CONCLUSION: Drilling the femoral tunnel through the low anteromedial portal
      resulted in a more oblique femoral tunnel position compared to the TT technique.
      Clinically, the low anteromedial portal may allow to better restore the anatomic
      orientation of the ACL.

PMID- 22476527
TI  - Structural and functional analysis of the semitendinosus tendon after harvest for
      soft tissue reconstructive procedures: a dynamic ultrasonographic study.
AB  - PURPOSE: To assess the potential for regeneration of the hamstring tendons after
      harvesting for various soft tissue reconstructive procedures, this study uses
      dynamic, high-resolution ultrasound to evaluate the presence of any tissue in the
      harvest gap and to characterize tissue functionality. METHODS: Patients who
      underwent ACL reconstruction using ipsilateral hamstring autograft were
      identified in the database of a single surgeon. Dynamic 12-MHz sonographic
      imaging was used to evaluate the ipsilateral and contralateral (control)
      semitendinosus tendons from their insertion sites to proximal muscle bellies. The
      presence or absence and echogenicity of tissue in the harvest defect, tissue
      appearance, degree of retraction of the proximal tendon stump, thickness of gap
      tissue, and motion of the proximal tendon stump were recorded. Data were analysed
      with Wilcoxon-Mann-Whitney, sign or binomial tests, with significance of P <
      0.05. RESULTS: Eighteen knees in 15 patients (aged 17-51 years) were studied. The
      proximal amputated stump was retracted an average of 9.0 +/- 7.6 cm (range, 0-18
      cm; P = 0.0063). With dynamic testing, 9 of 15 knees demonstrated decreased
      excursion of the proximal tendon stump when compared to the native, contralateral
      muscle-tendon unit (P = 0.0039). Tissue was detected in the harvest gap in nine
      knees, five of which had harvest gap tissue with a disorganized appearance
      compared to the native tendon (P < 0.0001). Six of these nine knees had tissue in
      the gap demonstrating either less or no excursion with active knee flexion when
      compared to the native, contralateral side (P = 0.0313). CONCLUSIONS: The
      presence of tissue in the harvest gap after ACL reconstruction is variable. When
      tissue is present, there is proximal retraction of the musculotendinous junction
      and disorganized appearance of the tissue that does not demonstrate normal
      excursion or physiological function similar to the native muscle-tendon unit.
      LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 22476528
TI  - Influence of soft tissues on the proximal bony tibial slope measured with two
      dimensional MRI.
AB  - PURPOSE: Despite increasing interest in the functional anatomy of the menisci,
      little information is available regarding the relationship between the tibial
      slope and the menisci. It was hypothesized that the meniscus would reduce the
      differences in slope between the medial and lateral compartments and would
      mitigate the effects of age and gender on the tibial slope. METHODS: MRI sagittal
      images from 101 patients were used in this study. The angle between a line
      tangent to the medial and lateral tibial bony slope and the proximal tibial
      anatomical axis was measured on sagittal MRI images (bony slope). The angle
      between the tangent line to the highest point of the anterior and posterior horn
      of the meniscus and the proximal tibial anatomical axis was also determined (soft
      tissue slope). The measurements were carried out twice by two observers. The
      influence of gender and age on these parameters was analysed. RESULTS: Repeated
      measures analysis of variance showed good inter- and intra-observer reliability
      for both bony and soft tissue slope (ICC (0.87-0.93) and (0.91-0.97) for inter-
      and intra-observer reliability, respectively). In both compartments, the soft
      tissue significantly reduced the tibial slope towards the horizontal plane. In
      addition, the soft tissue slope was significantly more horizontal in the lateral
      compartment compared to the medial compartment (p < 0.01). These differences were
      not influenced by age or gender. CONCLUSION: The menisci of the knee generate a
      more horizontal tibial slope when measured on MRI. The soft tissue slope is more
      horizontal in the lateral compartment of the knee compared to the medial
      compartment. LEVEL OF EVIDENCE: Diagnostic, Level III.

PMID- 22476529
TI  - Henipaviruses in their natural animal hosts.
AB  - Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within
      the family Paramyxoviridae, and are classified as biosafety level 4 pathogens due
      to their high case fatality rate following human infection and because of the
      lack of effective vaccines or therapy. Both viruses emerged from their natural
      reservoir during the last decade of the twentieth century, causing severe disease
      in humans, horses and swine, and infecting a number of other mammalian species.
      The current review summarizes our up to date understanding of pathology and
      pathogenesis in the natural reservoir species, the Pteropus bat, and in the
      equine and porcine spill over species.

PMID- 22476530
TI  - Ecological aspects of hendra virus.
AB  - Hendra virus, a novel and fatally zoonotic member of the family Paramyxoviridae,
      was first described in Australia in 1994. Periodic spillover from its natural
      host (fruit bats) results in catastrophic disease in horses and occasionally the
      subsequent infection of humans. Prior to 2011, 14 equine incidents involving
      seven human cases (four fatal) were recorded. The year 2011 saw a dramatic
      departure from the sporadic incidents of the previous 16 years, with a cluster of
      18 incidents in a single 3-month period. The fundamental difference in 2011 was
      the total number of incidents, the geographic clustering, and the expanded
      geographic range. The 2011 cluster more than doubled the total number of
      incidents previously reported, and poses the possibility of a new HeV infection
      paradigm. Epidemiologic evidence suggests that compelling additional host and/or
      environmental factors were at play.

PMID- 22476531
TI  - The influence of Nd:YAG laser irradiation on Fluoroptic(r) temperature
      measurement: an experimental evaluation.
AB  - The aim of this study was to experimentally evaluate temperature monitoring with
      a Fluoroptic(r) temperature probe in the presence of laser irradiation from a
      Nd:YAG laser, which is mainly used for clinical MR-guided laser-induced
      interstitial thermotherapy. Temperature measurements were performed using a
      Fluoroptic(r) probe in comparison to a thermocouple probe in a gel phantom and an
      ex vivo pig liver at distances of 6.5 to 14 mm to the laser applicator (laser
      energy of 30.8 W). To evaluate the artifacts in the temperature measurement, the
      laser was turned on and off three times during the entire experiment. A
      comparison of the fiber-optic measurements with MR thermometry was also performed
      in pig liver by means of the proton resonance frequency method at a distance of 6
      mm. Depending on the distance, the temperature measured by the fiber-optic probe
      deviated from the thermocouple probe temperature. The phantom deviations of 0.4
      to 34.3 % were observed. The differences in the liver were smaller and ranged
      from 1.6 to 5.2 %. The Bland-Altman mean of differences between MR and fiber
      optic temperature measurements was 0.02  degrees C and the 95 % limits of
      agreement value was +/- 2.25 degrees C. During laser application, considerable
      artifacts occurred in the Fluoroptic(r) measurements in short distances which was
      induced by laser energy absorption by the probe coating. No artifacts were
      verifiable at a distance of 14 mm in both mediums. The good conformity with MR
      thermometry resulted from the shorter turn-on times of the laser since the laser
      irradiation had only a minor effect on the measurements.

PMID- 22476532
TI  - A comprehensive appraisal of meta-analyses focusing on nonsurgical treatments
      aimed at decreasing perioperative mortality or major cardiac complications.
AB  - PURPOSE: Millions of patients worldwide who undergo surgical procedures face
      significant morbidity and mortality risks. Several systematic reviews have been
      performed on ancillary treatments aimed at improving surgical outcomes, but their
      features and scholarly impact are unclear. We describe characteristics of meta
      analyses on ancillary treatments aimed at improving surgical outcomes and explore
      factors associated with scholarly citations. METHODS: Systematic reviews
      published up to 2008 were searched without language restrictions in
      MEDLINE/PubMed. Reviews focusing on nonsurgical treatments aimed at decreasing
      mortality or major cardiac complications were included. Associations between
      content, quality, and bibliometric details and scholarly citations in several
      indexes were systematically appraised. RESULTS: From 2,239 citations, 84
      systematic reviews were identified. Patients most commonly underwent
      cardiovascular surgery (40.2%), and were tested for cardiovascular drugs (25.8%),
      with placebo acting as control (38.1%). Internal validity appeared largely
      robust, as most (50.5%) reviews were at low risk of bias. Normalized yearly
      citations for the included reviews ranged between 5.6 in Google Scholar and 4.3
      in Web of Science. Multivariable analysis showed that citations were
      significantly and positively associated with number of authors, North American
      corresponding author, number of studies included, number of patients included,
      noncardiothoracic surgical scope, explicit funding, and lack of competing
      interests (all p < 0.05). CONCLUSIONS: Systematic reviews currently represent a
      key element in defining state of the art ancillary treatments of patients
      undergoing surgery. However, the citation success of available meta-analyses is
      not significantly associated with prognostically relevant findings or quality
      features.

PMID- 22476533
TI  - Cervical impalement injury to a child by a chopstick diagnosed with computed
      tomography and ultrasonography.
AB  - Injuries penetrating into the floor of the mouth in the oral cavity caused by
      chopsticks are rare. We report a case of neck impalement injury caused by a
      wooden chopstick fragment penetrating all the way through the base of the tongue.
      An 18-month-old boy fell off his chair when he was biting on a wooden chopstick.
      Four centimeters of the chopstick broke off but could not be found, so he was
      brought to our emergency department with minor bleeding from the tongue. Computed
      tomography (CT) revealed that the fragment had penetrated through the tongue into
      the neck. Ultrasonography (US) revealed that the fragment was in close proximity
      to the common carotid artery. Surgery for the removal of the chopstick tip was
      uneventful, with minimal soft tissue trauma. Postoperative progress was
      satisfactory and without complications. Of particular interest is the sensitivity
      of US in outlining the broken chopstick fragment lodged in the neck. It is
      noteworthy that the contrast of the chopstick greatly varied between CT and US.

PMID- 22476534
TI  - Caspase-like enzymatic activity and the ascorbate-glutathione cycle participate
      in salt stress tolerance of maize conferred by exogenously applied nitric oxide.
AB  - Salinity stress causes ionic stress (mainly from high Na+ and Cl- levels) and
      osmotic stress (as a result of inhibition of water uptake by roots and amplified
      water loss from plant tissue), resulting in cell death and inhibition of growth
      and ultimately adversely reducing crop productivity. In this report, changes in
      root nitric oxide content, shoot and root biomass, root H2O2 content, root lipid
      peroxidation, root cell death, root caspase-like enzymatic activity, root
      antioxidant enzymatic activity and root ascorbate and glutathione contents/redox
      states were investigated in maize (Zea mays L. cv Silverking) after long-term (21
      d) salt stress (150 mM NaCl) with or without exogenously applied nitric oxide
      generated from the nitric oxide donor 2,2'-(Hydroxynitrosohydrazano)bis-ethane.
      In addition to reduced shoot and root biomass, salt stress increased the nitric
      oxide and H2O2 contents in the maize roots and resulted in elevated lipid
      peroxidation, caspase-like activity and cell death in the roots. Altered
      antioxidant enzymatic activities, along with changes in ascorbate and glutathione
      contents/redox status were observed in the roots in response to salt stress. The
      detrimental effects of salt stress in the roots were reversed by exogenously
      applied nitric oxide. These results demonstrate that exogenously applied nitric
      oxide confers salt stress tolerance in maize by reducing salt stress-induced
      oxidative stress and caspase-like activity through a process that limits
      accumulation of reactive oxygen species via enhanced antioxidant enzymatic
      activity.

PMID- 22476535
TI  - Educating nurses: a call for radical transformation-how far have we come?

PMID- 22476537
TI  - Therapeutic potential of induced and natural FoxP3(+) regulatory T cells for the
      treatment of Graft-versus-host disease.
AB  - Graft-versus-host disease (GvHD) remains a major complication after allogeneic
      hematopoietic stem-cell-transplantation. Present GvHD prophylaxis and treatment
      is still based on unspecific immunosuppressive drug therapy. Over the last
      decade, the potential of cell-based therapies involving the infusion of
      regulatory T cells has emerged as a feasible alternative approach for the
      treatment and prevention of GvHD. Here we review current efforts to translate
      data obtained in rodent models into clinical trials. Special emphasis is placed
      on the variety of strategies to generate sufficient numbers of alloantigen
      specific regulatory T cells for adoptive cell therapy. This can be achieved
      either by expansion or by induction of a regulatory phenotype in naive T cells.
      Stability of the immunosuppressive phenotype of transferred regulatory T cells
      even in the highly inflammatory environment of acute GvHD will be thereby a
      critical parameter for actual therapeutic application.

PMID- 22476538
TI  - Ezrin and BCAR1/p130Cas mediate breast cancer growth as 3-D spheroids.
AB  - CAS proteins and Ezrin, Radixin, Moesin (ERM) family members act as intracellular
      scaffolds and are involved in interactions with the cytoskeleton, respectively.
      Both protein families have previously been associated with metastasis and poor
      prognosis in cancer. Our group recently reported on the overexpression of
      EZR/VIL2 and BCAR1 and their protein products in breast carcinoma effusions
      compared to primary breast carcinoma. In the present study, the role of these two
      proteins was studied in semi-normal MCF10A cells and metastatic MDA-MB-231 breast
      carcinoma cells cultured in tri-dimensional (3-D) conditions that were
      hypothesized to reproduce the in vivo conditions of breast cancer metastasis.
      MCF10A cells formed spheroid-shaped colonies without any Matrigel invasion, while
      MDA-MB-231 cells displayed an invasive phenotype and showed satellite projections
      that bridged multiple cell colonies in 3-D culture. E-cadherin was expressed in
      MCF10A, but not in MDA-MB-231 cells. The temporal expression of ezrin and
      BCAR1/p130Cas at the mRNA and protein level differed in the two cell lines upon 3
      D culturing on Matrigel. Upregulation of BCAR1/p130cas was observed in the
      transition of MDA-MB-231 from attached to detached culture. Silencing of Ezrin
      and p130Cas in MDA-MB-231 cells by short hairpin RNA resulted in decreased
      invasive potential, and p130Cas silencing further resulted in smaller
      spheroid/colony formation. Our data show that MCF10A and MDA-MB-231 cells differ
      in their ability to form spheroids, in expression of E-cadherin and in the
      expression of Ezrin and BCAR1/p130Cas in 3-D cultures on Matrigel, suggesting a
      role in tumor progression in breast carcinoma.

PMID- 22476539
TI  - Quantitative modeling of the behaviour of microfluidic autoregulatory devices.
AB  - We develop a theoretical model for a fluidic current source consisting of a via,
      a detour channel, and a push-up type micro-valve. The model accurately describes
      the non-linear behaviour of this type of device, which has been previously
      measured experimentally. We show how various structural parameters and material
      properties of the device influence the saturated flow rate and the minimum
      driving pressure required for the device to function as a current source.
      Conversely, the model can be used to design a fluidic current source with a
      desired saturated flow rate and low operational pressure. The present model can
      be straightforwardly applied to microfluidic circuits composed of many functional
      autoregulatory devices.

PMID- 22476540
TI  - Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates
      invasion in cholangiocarcinoma cell lines in vitro.
AB  - PURPOSE: Cholangiocarcinoma is defined as a chronic liver disease with altered
      estrogen metabolism and could result in estrogen retention. Estrogenic response
      was known as a promoting factor in progression of some cancer. In this study, we
      determined the significant increase of estrogen level in cholangiocarcinoma
      patients' sera. METHODS: The estrogen levels in cholangiocarcinoma patients' sera
      were measured and correlated with clinical presentations. Estrogen receptor-alpha
      expressions in cholangiocarcinoma tissues were detected by immunohistochemistry
      method. KKU-100 and KKU-M213 cholangiocarcinoma cell lines were treated with
      17beta-estradiol and tested the proliferative and invasive effects. RESULTS: The
      estrogen levels showed positive correlations with serum bilirubin and alkaline
      phosphatase and a negative correlation with albumin. This study also showed an
      association with shorter survival times when patients with low and high serum
      estrogen levels were compared. In vitro studies demonstrated the effect of
      estrogen on cell proliferation and invasion in dose-dependent manners, which
      could be inhibited by tamoxifen, a clinical used estrogen antagonist. Invasion
      showed an association with the TFF1 gene expression and could be inhibited by
      small interfering RNA against TFF1 gene. Estrogen receptor-alpha was the main
      estrogen receptor that response to 17beta-estradiol stimulation. CONCLUSIONS:
      TFF1 trefoil protein could be one of the effectors for estrogen-induced invasion
      in cholangiocarcinoma via the estrogen receptor-alpha. These findings could lead
      to an understanding of the mechanism of cholangiocarcinoma progression.

PMID- 22476541
TI  - A simple and rapid colorimetric method for determination of phytate in urine.
AB  - Phytate is a natural product present in urine and biological fluids that is
      associated with health benefits, such as the prevention of calcium renal stone
      formation. The available methods for phytate analysis in urine all require
      elaborate instrumentation and cannot be routinely applied in clinical
      laboratories. Here, we describe a simple procedure for urinary phytate
      determination, employing colorimetric detection. Our method requires purification
      and preconcentration of phytate via solid-phase extraction prior to colorimetric
      detection employing Fe(III)-thiocyanate. The working linear range of the assay is
      0-5 MUM phytate. The limit of detection is 0.055 MUM. The relative standard
      deviation obtained upon assay of samples containing 2 MUM phytate was 3.5 %.
      Several urine samples were analyzed using an alternative method based on the
      detection of phosphorus; the results of the two assays were comparable. Our novel
      method of phytate analysis in human urine is simple, rapid (3 h for 10 samples),
      accurate, precise, reliable, and highly sensitive. The assay can be run in most
      analytical laboratories and does not require sophisticated instrumentation.

PMID- 22476543
TI  - An International Urogynecological Association (IUGA)/International Continence
      Society (ICS) joint report on the terminology for reporting outcomes of surgical
      procedures for pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Standardized terminology has yet to be developed for
      reporting the outcomes for surgery for pelvic organ prolapse (POP). METHODS: This
      report combines the input of the Terminology and Standardization Committees of
      the International Urogynecological Association (IUGA) and the International
      Continence Society (ICS) and a joint Working Group on this topic, as well as
      expert external referees. The aim was to present a standardized terminology for
      the definitions of surgery and propose a structure for reporting the outcomes of
      surgical procedures for POP. An extensive drafting and review process was
      undertaken, as well as open review on both IUGA and ICS websites. RESULTS: A
      terminology report was developed outlining the recommended structure for
      reporting outcomes of surgical trials involving POP. This document does not
      define success and failure. The report includes patient-reported, subjective and
      objective outcomes to enable researchers to report on their results and compare
      them with other studies. CONCLUSIONS: A consensus-based method for standardizing
      terminology for reporting outcome measures of POP surgery was developed to aid
      clinicians working in this area of research.

PMID- 22476544
TI  - Monogamy and secondary sexual partnerships among Afro-Amerindian immigrant women
      in New York City: a qualitative study.
AB  - In New York City, HIV is increasingly concentrated in the foreign-born
      population, necessitating a greater exploration of the mechanisms through which
      changes in behavior and risk for HIV occur within migrant populations. Interviews
      were conducted with 22 Honduran-born Garifuna women to explore partnerships,
      sexual behaviors, and HIV risk in the context of migration, and transcripts were
      coded by thematic analysis procedures. Five themes emerged: (1) migration ends
      relationships, (2) new relationships in the U.S. form because of material and
      psychological needs, (3) secondary sexual partnerships are a man's issue, (4)
      female secondary sexual partnership participation as a marker of equality, and
      (5) monogamy due to a lack of time. These findings suggest that greater attention
      be paid to women's participation in secondary sexual partnerships for purposes
      other than economic need, and demonstrate a need for HIV interventions that are
      based in an understanding of how the social context of migration affects sexual
      behaviors.

PMID- 22476545
TI  - A water soluble and air-stable tripalladium cluster.
AB  - Complexation of 2,7-dipyridin-2-ylnaphthyridine (bpnp) with a mixture of
      (PhCN)(2)PdCl(2) and Pd(2)(dba)(3) resulted in the formation of a water soluble
      and air-stable tripalladium cluster [Pd(3)(bpnp)(2)Cl(2)]Cl(2), which was
      characterized by NMR spectroscopic and X-ray crystallographic analyses.

PMID- 22476546
TI  - Two eyes see more than one: double echo stereoscopic MRA for rapid 3D
      visualization of vascular structures.
AB  - OBJECT: A three-dimensional (3D) visualization of the target region during
      intravascular interventions in real-time is challenging since the acquisition of
      a time-consuming 3D dataset is required. In this work, a novel stereoscopic
      double echo sequence for achieving 3D depth perception by sampling only two
      oblique projection images is presented. MATERIALS AND METHODS: A double echo (DE)
      FLASH pulse sequence was developed to acquire continuously stereoscopic image
      pairs of the vascular target anatomy. Stereo image data were displayed on a
      stereoscopic 3D LCD monitor in real time after image reconstruction. Phantom
      experiments followed by a depth perception test were performed to assess the
      usability of the stereo image pairs for 3D visualization. In an animal experiment
      the sequence was tested in vivo and was compared with a slower interleaved (IL)
      sequence variant. RESULTS: In the phantom experiments an SNR difference of 6 %
      between left and right image was found which did not influence the depth
      perception. The DE acquisition was superior to the IL sequence (SNR(DE) = 10.3,
      2.3 images/s over SNR(IL) = 7.1, 1.7 images/s), and during contrast enhancement
      the abdominal arterial vasculature was clearly perceived as a 3D structure.
      CONCLUSION: A novel stereoscopic DE pulse sequence can be utilized for the fast
      3D stereoscopic visualization of vascular structures in real-time.

PMID- 22476547
TI  - Transformation of malathion by Lysinibacillus sp. isolated from soil.
AB  - An axenic bacterial strain, Lysinibacillus sp. KB1, was isolated from malathion
      contaminated soil. It tolerated malathion up to 0.15 % and, under aerobic
      conditions, utilized it as sole carbon source. 20 % malathion and 47 % malaoxon
      were degraded out of the initially provided malathion. Two metabolites, mal
      monocarboxylic acid and mal-dicarboxylic acid, were detected within 7 days at 30 
      degrees C. Esterase activity of the strain was 240 +/- 2.5 U/ml after 7 days of
      growth. Sterilized soil mixed with malathion showed rapid degradation of
      malathion when inoculated with strain KB1 as compared to the uninoculated soil.

PMID- 22476548
TI  - Neural differentiation of mouse embryonic stem cells on conductive nanofiber
      scaffolds.
AB  - Nerve tissue engineering requires suitable precursor cells as well as the
      necessary biochemical and physical cues to guide neurite extension and tissue
      development. An ideal scaffold for neural regeneration would be both fibrous and
      electrically conductive. We have contrasted the growth and neural differentiation
      of mouse embryonic stem cells on three different aligned nanofiber scaffolds
      composed of poly L: -lactic acid supplemented with either single- or multi-walled
      carbon-nanotubes. The addition of the nanotubes conferred conductivity to the
      nanofibers and promoted mESC neural differentiation as evidenced by an increased
      mature neuronal markers expression. We propose that the conductive scaffold could
      be a useful tool for the generation of neural tissue mimics in vitro and
      potentially as a scaffold for the repair of neural defects in vivo.

PMID- 22476549
TI  - An alternative method for cDNA cloning from surrogate eukaryotic cells
      transfected with the corresponding genomic DNA.
AB  - cDNA is widely used in gene function elucidation and/or transgenics research but
      often suitable tissues or cells from which to isolate mRNA for reverse
      transcription are unavailable. Here, an alternative method for cDNA cloning is
      described and tested by cloning the cDNA of human LALBA (human alpha-lactalbumin)
      from genomic DNA. First, genomic DNA containing all of the coding exons was
      cloned from human peripheral blood and inserted into a eukaryotic expression
      vector. Next, by delivering the plasmids into either 293T or fibroblast cells,
      surrogate cells were constructed. Finally, the total RNA was extracted from the
      surrogate cells and cDNA was obtained by RT-PCR. The human LALBA cDNA that was
      obtained was compared with the corresponding mRNA published in GenBank. The
      comparison showed that the two sequences were identical. The novel method for
      cDNA cloning from surrogate eukaryotic cells described here uses well-established
      techniques that are feasible and simple to use. We anticipate that this
      alternative method will have widespread applications.

PMID- 22476551
TI  - Precipitation of Trichoderma reesei commercial cellulase preparations under
      standard enzymatic hydrolysis conditions for lignocelluloses.
AB  - Comparative studies between commercial Trichoderma reesei cellulase preparations
      show that, depending on the preparation and loading, total protein precipitation
      can be as high as 30 % under standard hydrolysis conditions used for
      lignocellulosic materials. ATR-IR and SDS-PAGE data verify precipitates are
      protein-based and contain key cell wall hydrolyzing enzymes. Precipitation
      increased considerably with incubation temperature; roughly 50-150 % increase
      from 40 to 50  degrees C and 800 % greater at 60  degrees C. All of the reported
      protein losses translated into significant, and often drastic, losses in activity
      on related 4-nitrophenyl substrates. In addition, supplementation with the non
      ionic surfactant PEG 6,000 decreased precipitation up to 80 % in 24 h
      precipitation levels. Protein precipitation is potentially substantial during
      enzymatic hydrolysis of lignocelluloses and should be accounted for during
      lignocellulose conversion process design, particularly when enzyme recycling is
      considered.

PMID- 22476552
TI  - The SAMPL3 blind prediction challenge: transfer energy overview.
AB  - Prediction of the free energy of solvation of a small molecule, or its transfer
      energy, is a necessary step along the path towards calculating the interactions
      between molecules that occur in an aqueous environment. A set of these transfer
      energies were gathered from the literature for series of chlorinated molecules
      with varying numbers of chlorines based on ethane, biphenyl, and dibenzo-p
      dioxin. This focused set of molecules were then provided as a blinded challenge
      to assess the ability of current computational solvation methods to accurately
      model the interactions between water and increasingly chlorinated compounds. This
      was presented as part of the SAMPL3 challenge, which represented the fourth
      iterative blind prediction challenge involving transfer energies. The results of
      this exercise demonstrate that the field in general has difficulty predicting the
      transfer energies of more highly chlorinated compounds, and that methods seem to
      be erring in the same direction.

PMID- 22476553
TI  - Results of pulsed radiofrequency technique with two laterally placed electrodes
      in the annulus in patients with chronic lumbar discogenic pain.
AB  - Discogenic pain is an important cause of low back pain (LBP). We have developed a
      pulsed radiofrequency (P-RF) technique, using two electrodes placed bilaterally
      in the annulus, for applying radiofrequency current in the disc (bi-annular P-RF
      disc method). The purpose of this study was to investigate the effect of the bi
      annular P-RF disc method, using Diskit needles (Neurotherm, Middleton, MA, USA)
      in patients with discogenic LBP. The subjects were 15 patients with a mean age of
      37.3 +/- 8.63 years with chronic discogenic lower back pain that was not
      responsive to aggressive nonoperative care. Two Diskit II needles (15-cm length,
      20G needles with a 20-mm active tip) were placed bilaterally in the annulus in
      the disc. Pulsed radiofrequency was applied for 12 min at a setting of 5 * 50
      ms/s and 60 V. The pain intensity scores on a 0-10 numeric rating scale (NRS) and
      the Roland-Morris Disability Questionnaire (RMDQ) were measured pretreatment, and
      at 1 week and 1, 3, and 6 months post-treatment. The mean pain severity score
      (NRS) improved from 7.27 +/- 0.58 pretreatment to 2.5 +/- 0.94 at the 6-month
      follow-up (p < 0.01). The RMDQ showed significant (p < 0.01) improvement, from
      10.70 +/- 2.35 pretreatment to 2.10 +/- 1.85 at the 6-month follow up (p < 0.01).
      The bi-annular P-RF disc method with consecutive P-RF 5/5/60 V, 12-min (with
      Diskit needle), appears to be a safe, minimally invasive treatment option for
      patients with chronic discogenic LBP.

PMID- 22476554
TI  - Experience of Advate rAHF-PFM in previously untreated patients and minimally
      treated patients with haemophilia A.
AB  - We report a prospective trial of 55 previously untreated patients (PUPs) and
      minimally treated patients (MTPs) with severe/moderately severe haemophilia A
      (baseline factor VIII [FVIII] <=2%) treated with a single FVIII replacement
      product. It was the objective of this study to evaluate the immunogenicity,
      efficacy, and safety of rAHF-PFM (Advate(r)). On-demand or prophylactic treatment
      regimens were determined at the discretion of the investigator. rAHF-PFM was also
      permitted for perioperative management. There were 633 bleeding episodes (BEs),
      including 517 treated, and 466 rated for efficacy. Haemostatic efficacy was
      considered excellent/good in 93% of 466 rated treatments. Of 517 treated BEs,
      463/517 (90%) were managed with one (356/517 [69%]) or two infusions (107/517
      [21%]). There were 27 surgeries. Intraoperative (n=22) and postoperative (n=25)
      haemostatic efficacies were considered excellent or good in 100% of rated
      surgeries. Related serious adverse events (SAEs) were inhibitor development in
      16/55 (29.1%) subjects who received at least one infusion of rAHF-PFM. Non
      serious, related adverse events (AEs) were few in number (14 in eight subjects).
      The odds ratio (OR [95% Confidence Interval, CI]) of developing inhibitors was
      significantly higher in subjects with a family history of inhibitor (4.95[1.29
      19.06]), non-Caucasian ethnicity (4.18, [1.18-14.82]), and intensive treatment at
      high dose (4.5 [1.05-19.25]) within <=20 exposure days (EDs). In conclusion, rAHF
      PFM was safe and effective for the management and perioperative coverage of
      PUPs/MTPs with severe/moderately severe haemophilia A. This report supports
      previous findings from studies in which family history of inhibitor, non
      Caucasian ethnicity, and high intensity treatment were associated with high risk
      of inhibitor development.

PMID- 22476556
TI  - Animal challenge models of henipavirus infection and pathogenesis.
AB  - The henipaviruses, Hendra virus (HeV), and Nipah virus (NiV), are enigmatic
      emerging pathogens that causes severe and often fatal neurologic and/or
      respiratory disease in both animals and humans. Amongst people, case fatality
      rates range between 40 and 75% and there are no vaccines or treatments approved
      for human use. A number of species of animals including guinea pigs, hamsters,
      cats, ferrets, pigs, and African green monkeys have been employed as animal
      models of human henipavirus infection. Here, we review the development of animal
      models for henipavirus infection, discuss the pathology and pathogenesis of these
      models, and assess the utility of each model to recapitulate important aspects of
      henipavirus-mediated disease seen in humans.

PMID- 22476557
TI  - The gut microflora and its variety of roles in health and disease.
AB  - The intestinal microbiota is a complex community of microorganisms that colonizes
      the gastrointestinal tract. The composition of the intestinal microbiota and the
      number of microorganisms differ in dependency of the local environmental
      conditions. The intestinal microbiota has an important impact on the development
      of the intestinal architecture and function, it influences the development of the
      gut-associated immune system, and epithelial cell functions. One of the most
      important functions of the intestinal microbiota is the prevention of bacterial
      overgrowth and susceptibility to infection with enteropathogenic organisms.
      Additionally, the intestinale microbiota plays a crucial role in the development
      of the systemic immunity and has an important influence on the host nutrition and
      metabolism. However, in genetically predisposed hosts, the intestinal microbiota
      is involved in the pathophysiology of inflammatory bowel diseases and pouchitis.
      Additionally, recent studies suggest that there might be an inflammation
      triggering effect of the intestinal microbiota in necrotizing enterocolitis.
      Here, we give an overview of the intestinal microbiota and its variety of roles
      in health and disease.

PMID- 22476558
TI  - Prostate cancer epidemiology in the United States.
AB  - BACKGROUND: Prostate cancer is a significant public health issue in the United
      States. It is the most commonly diagnosed non-skin cancer and the second leading
      cause of cancer death. The American Cancer Society estimates that in 2011,
      240,890 men were diagnosed with prostate cancer and 33,720 men died of it.
      METHODS: A review of the peer-reviewed literature was conducted: American Cancer
      Society, National Cancer Institute Surveillance, Epidemiology and End Results.
      Program data were assessed to describe trends in incidence, mortality, and
      survival rates and look at other predictors of risk of prostate cancer diagnosis
      and death. RESULTS: Since 1985, there have been significant changing trends in
      prostate cancer incidence, mortality, and survival rates, as well as changes in
      the age distribution of the population diagnosed and even in the distribution of
      pathologies at diagnosis. Major risk factors for diagnosis include age, family
      history, race, and screening behavior. CONCLUSION: While prostate cancer remains
      largely a disease diagnosed in older men (over age 65), screening has increased
      risk of diagnosis among men in their 40s and 50s. The incidence rates and 5-year
      survival rates are heavily influenced by the introduction of serum prostate
      specific antigen (PSA) and widespread screening. The effects of PSA usage and
      screening on mortality rates are less certain. Outcome studies among men treated
      with radical prostatectomy show that greater than 30% relapse rates are common.
      This suggests that many men who are diagnosed with "localized early stage
      disease" actually have "apparently localized early stage disease," which is
      really low volume metastatic disease.

PMID- 22476559
TI  - Identification and molecular analysis of pathogenic yeasts in droppings of
      domestic pigeons in Beijing, China.
AB  - Feral pigeons are known as reservoirs of pathogenic yeasts that cause
      opportunistic infections in human. In the outskirts of Beijing, China, pigeons
      are more frequently raised at homes than are encountered in public areas. Many
      studies have focused on the presence of pathogenic yeasts in the excreta (fresh
      or withered) of a variety kinds of birds, pigeon crop and cloacae. One hundred
      and forty-three samples of fresh droppings were collected from three suburban
      pigeon-raising homes in an area of northern Beijing, China. The internal
      transcribed sequences (ITS) of all strains (except for 8 strains of Rhodotorula
      sp. ) were sequenced and compared with those of the databases of the National
      Center for Biotechnology Information website ( http://www.ncbi.nlm.nih.gov )
      using the Basic Local Alignment Search Tool (BLAST). Yeasts representing 8
      genera, Cryptococcus, Filobasidium, Rhodotorula, Candida, Debaryomyces,
      Saccaromyces, Trichosporon and Sporidiobolus, were identified from 120 isolates.
      Cryptococcus was the most prolific genera represented by eight species. The
      populations of yeast species isolated from fresh pigeon droppings were different
      among homes. Although it is well established that Cryptococcus neoformans exists
      mainly in old pigeon guano, several C. neoformans strains were still isolated
      from fresh pigeon excreta, providing a clue that live cryptococcal cells could
      move through the gastrointestinal tract of the pigeons. Eight genera identified
      from fresh droppings of domestic pigeons further confirm that pigeons serve as
      reservoirs, carriers and even spreaders of Cryptococcus species and other
      medically significant yeasts. The proportion of pathogenic yeasts in all isolates
      is more than 90 %.

PMID- 22476560
TI  - Impact of T-ACASI on Survey Measurements of Subjective Phenomena.
AB  - Numerous studies have shown that audio-computer-assisted self-interviewing (audio
      CASI) and telephone audio-CASI (T-ACASI) technologies yield increased reporting
      of sensitive and stigmatized objective phenomena such as sexual and drug use
      behaviors. Little attention has been given, however, to the impact of these
      technologies on the measurement of subjective phenomena (attitudes, opinions,
      feelings, etc.). This article reports results for the seven subjective
      measurements included in the National STD and Behavior Measurement Experiment
      (NSBME). NSBME drew probability samples of USA and Baltimore adults (Ns = 1,543
      and 744, respectively) and randomized these respondents to be interviewed by T
      ACASI or telephone interviewer-administered questioning (T-IAQ). Response
      distributions for all subjective measurements obtained by T-ACASI diverge from
      those obtained by human telephone interviewers. For six of our seven ordinal
      scaled measurements, this divergence involved shifting responses directionally
      along the ordinal scale, as opposed to a nondirectional redistribution among
      response categories. When interviewed by T-ACASI, respondents were more
      supportive of traditional gender roles and corporal punishment, less supportive
      of integrated neighborhoods and same-gender sex, and more likely to agree that
      occasional marijuana use is harmless and to describe themselves as attractive.
      The majority of these results suggest that telephone survey respondents may
      provide more "tolerant" and "socially liberal" responses to human interviewers
      than to a T-ACASI computer. Similarly, although the evidence is not entirely
      consistent, the impact of T-ACASI appears to increase with the social
      vulnerability of the population surveyed.

PMID- 22476561
TI  - Promoter -2518 single nucleotide polymorphism of monocyte chemoattractant protein
      1 is associated with clinical severity in Behcet's disease.
AB  - OBJECTIVE: We investigated whether promoter -2518 single nucleotide polymorphism
      (SNP) of the monocyte chemoattractant protein-1 (MCP-1) gene contributes to
      susceptibility and clinical features or severity in Behcet's disease (BD)
      patients. METHODS: One hundred and thirty-two BD patients and 113 healthy
      subjects, matched by sex and age, were enrolled. Promoter -2518 polymorphism of
      the MCP-1 gene was analyzed using automated sequencing. Clinical severity in BD
      patients was classified into mild, moderate, and severe features and assessed by
      total severity scores. Clinical features and severity was also compared according
      to genotypes using either the chi-squared or Fisher's exact test and Mann-Whitney
      test, as indicated. RESULTS: There were no significant differences in alleles (G
      allele vs. A allele, p=0.845) and genotypes with -2518 SNP (GG vs. GA vs. AA,
      p=0.916) between BD patients and controls. No clinical features were associated
      with genotypes with -2518 polymorphism of MCP-1. However, the frequency of either
      GA or AA genotype in patients with moderate lesions and moderate to severe
      lesions was significantly increased compared with that in patients with the GG
      genotype (p=0.044 and p=0.038, respectively). Total severity scores in the AA
      genotype were higher than those in the GG and GA genotypes (p=0.039 and p=0.003,
      respectively). Moreover, patients with either the GA or AA genotype had higher
      scores than those with the GG genotype (p=0.041). CONCLUSIONS: This study
      demonstrated that genotypes with A allele with -2518 polymorphism of the MCP-1
      gene might have increased risk of severity of clinical features, but not
      susceptibility to BD.

PMID- 22476562
TI  - A rapid fluorescent screening method for cellular sensitivity to anti-cancer
      compound.
AB  - The tetrazolium salts (MTT, XTT, MTS, WST) based colorimetric assay or resazurin
      based fluorimetric assay are currently typical methods for cell sensitivity
      determination to anticancer compounds. We presented here a new rapid method for
      this purpose. This method uses a fluorescent dye named DCFH-DA which is
      previously taken as a intracellular probe for measurement of H(2)O(2) levels
      within a cell. The application basis for this method lies in two facts: the
      membrane permeable feature of the final metabolite of DCFH-DA inside a cell, and
      the linearity relationship between cell number and H(2)O(2) level. The results
      showed that there was a perfect association between cell number and fluorescent
      intensity determined by the DCFH-DA method, no matter whether using resuspended
      or adherent cells, and further 50% concentration of inhibition (IC(50))
      comparison between data obtained by DCFH-DA method or MTT method using a positive
      known anticancer compound Baicalin showed that there were no significant
      differences in cellular sensitivity determination to compound Baicalin though
      there existed a relatively higher coefficient of variation of IC(50) by the DCFH
      DA method than that by the MTT method. Thus our data indicate that DCFH-DA might
      not only be a fine reagent for determination of H(2)O(2) levels in cells but also
      an ideal fluorescent dye for cellular sensitivity test of anti-cancer compounds,
      and may be suitable for primary high-throughput drugs screening.

PMID- 22476563
TI  - VEGF(165) expressing bone marrow mesenchymal stem cells differentiate into
      hepatocytes under HGF and EGF induction in vitro.
AB  - A short half-life and low levels of growth factors in an injured microenvironment
      necessitates the sustainable delivery of growth factors and stem cells to augment
      the regeneration of injured tissues. Our aim was to investigate the ability of
      VEGF(165) expressing bone marrow mesenchymal stem cells (BMMSCs) to differentiate
      into hepatocytes when cultured with hepatocyte growth factor (HGF) and epidermal
      growth factor (EGF) in vitro. We isolated, cultured and identified rabbit BMMSCs,
      then electroporated the BMMSCs with VEGF(165)-pCMV6-AC-GFP plasmid. G418 was used
      to select transfected cells and the efficiency was up to 70%. The groups were
      then divided as follows: Group A was electroporated with pCMV6-AC-GFP plasmid +
      HGF + EGF and Group B was electroporated with VEGF(165)-pCMV6-AC-GFP plasmid +HGF
      + EGF. After 14 days, BMMSCs were induced into short spindle and polygonal cells.
      Alpha-fetoprotein (AFP) was positive and albumin (ALB) was negative in Group A,
      while both AFP and ALB were positive in group B on day 10. AFP and ALB in both
      groups were positive on day 20, but the quantity of AFP in group B decreased with
      prolonged time and was about 43.5% less than group A. The quantity of the ALB
      gene was  increased with prolonged time in both groups. However, there was no
      significant difference between group A and B on day 10 and 20. Our results
      demonstrated that VEGF(165)-pCMV6-AC-GFP plasmid modified BMMSCs still had the
      ability to differentiate into hepatocytes. The VEGF(165) gene promoted BMMSCs to
      differentiate into hepatocyte-like cells under the induction of HGF and EGF, and
      reduced the differentiation time. These results have implications for cell
      therapies.

PMID- 22476565
TI  - Short-term changes of metal availability in soil. Part I: comparing sludge
      amended with metal-spiked soils.
AB  - Sewage sludge application to soils is regulated by its total metal content.
      However, the real risk of metals is determined by the fraction that is
      biologically available. The available fraction is highly related to the strength
      of metal binding by the matrix, which is a dynamic process. The evaluation of the
      fate of metals in time can contribute increased accuracy of ecological risk
      assessment. Aiming to evaluate short-term changes in metal availability when
      metals were applied to soil directly (metal-spiked) or by way of an organic
      matrix (sludge-amended), a laboratory experiment was performed using open
      microcosms filled with agricultural soil. A concentration gradient of industrial
      sludge (11, 15, 55, and 75 t/ha) that was contaminated predominantly with
      chromium, copper, nickel, and zinc, or soil freshly spiked with the same
      concentrations of these metals, were applied on top of the agricultural soil.
      After 0, 3, 6, and 12 weeks, total (HNO(3) 69 %) and 0.01 M CaCl(2)-extractable
      metal concentrations in soil and metal content in the percolates were measured.
      Results demonstrated that comparison between sludge-amended and metal-spiked
      soils may give important information about the role of sludge matrix on metal
      mobility and availability in soil. In sludge-amended soils, extractable-metal
      concentrations were independent of the sludge concentration and did not change
      over time. In metal-spiked soils, metal extractability decreased with time due to
      ageing and transport of metals to deeper layers. In general, the sludge matrix
      increased the adsorption of metals, thus decreasing their mobility in soils.

PMID- 22476564
TI  - Characterization of Bombyx mori nucleopolyhedrovirus with a knockout of Bm17.
AB  - Open reading frame 17 (Bm17) gene of Bombyx mori nucleopolyhedrovirus is a highly
      conserved gene in lepidopteran nucleopolyhedroviruses, but its function remains
      unknown. In this report, transient-expression and superinfection assays indicated
      that BM17 localized in the nucleus and cytoplasm of infected BmN cells. To
      determine the role of Bm17 in baculovirus life cycle, we constructed a Bm17
      knockout virus and characterized its properties in cells. Analysis of the
      production and infection of budded virions, the level of viral DNA replication
      revealed showed that there was no significant difference among the mutant, the
      control, and the Bm17 repaired virus strains. These results suggest that BM17 is
      not essential for virus replication in cultured cells.

PMID- 22476566
TI  - qPCR quantification of Sphaerodes mycoparasitica biotrophic mycoparasite
      interaction with Fusarium graminearum: in vitro and in planta assays.
AB  - Sphaerodes mycoparasitica, a biotrophic mycoparasite of Fusarium species,
      improved wheat seed germination and seedling growth in vitro compared to
      Trichoderma harzianum, a necrotrophic mycoparasite. However, under phytotron
      conditions, both S. mycoparasitica and T. harzianum had positive impact on wheat
      seedlings growth in the presence of F. graminearum. Once exposed to the
      mycoparasites, the DNA quantity of F. graminearum in wheat root decreased.
      Observed shifts in DNA quantity using qPCR, a set of newly designed Sphaerodes
      specific SmyITS primers, as well as Trichoderma-TGP4 and Fusarium-Fg16 N primers,
      demonstrated the mycoparasite's biocontrol effectiveness in planta. In the
      presence of F. graminearum, the concentration of S. mycoparasitica DNA remained
      stable in the root, whereas the amount of T. harzianum DNA decreased. The
      toxicity assays indicated that S. mycoparasitica's mycelia withstand higher
      concentrations of deoxynivalenol, 3-acetyldeoxynivalenol, and zearalenone
      mycotoxins than T. harzianum mycelia. This study compares the ability of two
      fungi to improve the wheat growth, decrease the root colonization of Fusarium,
      and withstand mycotoxins.

PMID- 22476567
TI  - In vivo anthelmintic activity of Clerodendrum colebrookianum Walp., a
      traditionally used taenicidal plant in Northeast India.
AB  - Although there are several effective drugs available for the treatment of
      intestinal helminths, the fact remains that they continue to remain out of reach
      to a vast majority of people in the world, especially in developing countries. On
      the other hand, there are a great many herbal remedies that are effective against
      common intestinal worms and are easily available to common people in developing
      countries. Clerodendrum colebrookianum Walp. (Lamiaceae) is a perennial shrub
      which is native to South and Southeast Asia. Traditionally, the leaves of this
      plant are used by the indigenous people of Northeast India as a remedy for the
      treatment of intestinal tapeworm infections. The aim of this study was to
      evaluate and authenticate the anthelmintic efficacy of C. colebrookianum leaf
      extract in experimentally induced Hymenolepis diminuta (a zoonotic tapeworm)
      infections in Wistar rats. The efficacy of the plant extract was assessed by
      monitoring the eggs per gram of faeces (EPG) counts and worm recovery rates of
      experimental animals, following treatment with the leaf extract of this plant at
      three different doses, i.e. 200, 400 and 800 mg/kg body weight, each given singly
      for 5 days. The results obtained revealed that the leaf extract of C.
      colebrookianum possesses a dose-dependent efficacy against the larval, immature
      and adult stages of H. diminuta. However, the efficacy of the extract was found
      to be considerably high only against the adult stages of the parasite. For this
      stage, a single 800-mg/kg dose of extract, given for 5 days, resulted into 68.42%
      reduction in the EPG counts and 62.50% reduction in the worm counts in the
      extract-treated group of animals, as compared to the control. The reference drug,
      praziquantel (5 mg/kg, single dose), however, showed slightly better efficacy and
      caused 95.16 and 87.00% reductions in the EPG and worm counts of treated animals,
      respectively. Unlike the adult stages, the efficacy of the plant extract was
      recorded to be comparatively low against the larval and immature stages of the
      parasite, as the treatment of animals with the highest dose of extract (800
      mg/kg) could cause only 37.50 and 54.00% reductions in worm counts, respectively.
      The experimental evidence obtained in this study suggests that leaves of C.
      colebrookianum possess significant anthelminthic properties and supports their
      use against intestinal tapeworm infections in traditional medicine.

PMID- 22476568
TI  - Pilot evaluation of a health promotion program for African immigrant and refugee
      women: the UJAMBO Program.
AB  - The UJAMBO Program was a series of one session group workshops with Congolese and
      Somali women in the United States built around a DVD using African immigrant
      women's stories which provided basic information about mammography, pap smears
      and mental health services for trauma. The current study is an evaluation of the
      UJAMBO program addressing the impact on participants'knowledge of these health
      services and their intentions to use these services.

PMID- 22476569
TI  - The accuracy of meta-metacognitive judgments: regulating the realism of
      confidence.
AB  - Can people improve the realism of their confidence judgments about the
      correctness of their episodic memory reports by deselecting the least realistic
      judgments? An assumption of Koriat and Goldsmith's (Psychol Rev 103:490-517,
      1996) model is that confidence judgments regulate the reporting of memory
      reports. We tested whether this assumption generalizes to the regulation of the
      realism (accuracy) of confidence judgments. In two experiments, 270 adults in
      separate conditions answered 50 recognition and recall questions about the
      contents of a just-seen video. After each answer, they made confidence judgments
      about the answer's correctness. In Experiment 1, the participants in the
      recognition conditions significantly increased their absolute bias when they
      excluded 15 questions. In Experiment 2, the participants in the recall condition
      significantly improved their calibration. The results indicate that recall, more
      than recognition, offers valid cues for participants to increase the realism of
      their report. However, the effects were small with only weak support for the
      conclusion that people have some ability to regulate the realism in their
      confidence judgments.

PMID- 22476571
TI  - Development of a Korean version of the Cancer Therapy Satisfaction Questionnaire
      (CTSQ): cross-cultural adaptation, reliability, and validity.
AB  - PURPOSE: (1) To translate original English Cancer Therapy Satisfaction
      Questionnaire (CTSQ) into Korean and perform validation, (2) to compare CTSQ
      domains of expectations of therapy (ET), feelings about side effects (FSE), and
      satisfaction with therapy (SWT) by cancer therapy type. METHODS: Cross-cultural
      adaptation was performed according to guidelines: translation, back translation,
      focus-group, and field test. We performed validation with internal consistency by
      Cronbach's alpha and construct validity by exploratory factor analysis (EFA) with
      varimax rotation method. We compared each CTSQ domain between traditional Korean
      Medicine (TKM) and integrative cancer therapy (ICT) of combining western and TKM
      by two-sample t test. RESULTS: Cross-cultural adaptation produced no major
      modifications in the items and domains. A total of 102 outpatients were
      participated. Mean age was 51.9 +/- 12.4. Most were stage 4 (74.4 %) cancer. Mean
      scores of ET, FSE, and SWT were 81.2 +/- 15.7, 79.5 +/- 22.9, and 75.7 +/- 14.8,
      respectively. Cronbach's alpha of ET, FSE, and SWT were 0.86, 0.78, and 0.74,
      respectively. EFA loaded items on the three domains, which is very close to that
      of the original CTSQ. ET and SWT was similar, but FSE was significantly higher in
      TKM than ICT (87.5 +/- 19.3 vs. 74.9 +/- 23.5; p = 0.0054). CONCLUSIONS: Cross
      cultural adaptation was successful, and the adapted Korean CTSQ demonstrated good
      internal consistency and construct validity. Similar expectation and satisfaction
      was shown between the two types of therapy, but patient's reported feelings about
      side effects was significantly lower in patients receiving TKM than receiving
      ICT. Korean version of CTSQ can be used to evaluate Korean cancer patient's
      experiences receiving various cancer therapy types.

PMID- 22476573
TI  - Cross-cultural evaluation of the French version of the LEIPAD, a health-related
      quality of life instrument for use in the elderly living at home.
AB  - PURPOSE: To cross-culturally adapt a French version of the LEIPAD, a self
      administered questionnaire assessing the health-related quality of life (HRQoL)
      in adults aged 65 years and over living at home, and to evaluate its psychometric
      properties. METHODS: After having translated LEIPAD in accordance with
      guidelines, we studied psychometric properties: reliability and construct
      validity-factor analysis, relationships between items and scales, internal
      consistency, concurrent validity with the Medical Outcome Study Short-Form 36 and
      known-groups validity. RESULTS: The results obtained in a sample of 195 elderly
      from the general population showed very good acceptability, with response rates
      superior to 93 %. Exploratory factor analysis extracted eight factors providing a
      multidimensionality structure with five misclassifications of items in the seven
      theoretical scales. Good internal consistency (Cronbach's alpha ranging from 0.73
      and 0.86) and strong test-retest reliability (ICCs higher than 0.80 for six
      scales and 0.70 for one) were demonstrated. Concurrent validity with the SF-36
      showed small to strong expected correlations. CONCLUSION: This first evaluation
      of the French version of LEIPAD's psychometric properties provides evidence in
      construct validity and reliability. It would allow HRQoL assessment in clinical
      and common practice, and investigators would be able to take part in national and
      international research projects.

PMID- 22476574
TI  - Retinal detachment after phakic intraocular lens implantation in severe myopic
      eyes.
AB  - BACKGROUND: To report the incidence, clinical presentation, and surgical outcomes
      of retinal detachment in highly myopic patients corrected by implantation of
      phakic intraocular lenses (PIOLs). METHODS: This is a retrospective
      interventional non-comparative case series. A total of 530 highly myopic eyes
      that underwent PIOLs implantation were included in the study. All patients
      completed at least a 2-year follow-up after PIOL implantation. The incidence of
      retinal detachment (RD) and subsequent treatments were reviewed. The refractive
      errors, axial lengths, time between refractive surgery and RD detection,
      vitreoretinal findings, rate of retinal reattachment, and the pre- and
      postoperative best-corrected visual acuity (BCVA) were analyzed. RESULTS: The
      overall incidence of RD was 1.5 % (eight eyes of seven patients) with a mean time
      between PIOL implantation and detachment of 23.63 +/- 18.12 months (range, 2 days
      51 months). Mean spherical equivalent (SE) before PIOL implantation was -17.53 +/
      3.86 diopters (D) (range, -11.5D to -23.5D). Six patients underwent bilateral
      PIOL implantation. Five eyes were implanted with anterior chamber PIOLs and the
      other three received posterior chamber PIOLs. A traumatic history was presented
      before RD detection in four cases. Horseshoe tears, atrophic holes, or giant
      retinal tears were found in four (50 %), two (25 %), and two (25 %) eyes,
      respectively. Two eyes (25 %) underwent scleral buckling surgery, five eyes (62.5
      %) underwent pars plana vitrectomy surgery, and one eye (12.5 %) underwent both
      procedures. Anatomical retinal attachment was achieved after first RD surgery in
      seven eyes. Mean BCVA after PIOL implantation and before RD was 20/40 (decimal
      refraction, 0.51 +/- 0.31) compared to that of 20/80 (decimal refraction, 0.26 +/
      0.12) after the RD surgery. Mean follow-up after RD surgery was 20.63 +/- 12.93
      months (range, 8-42 months). CONCLUSIONS: The incidence of RD after PIOLs
      implantation is low. Its characteristics do not differ significantly from the
      natural history of RD in high myopic eyes. PIOL implantation for surgical
      correction of severe myopia does not seem to increase the risk of RD. Good visual
      prognosis can be obtained with early surgical intervention.

PMID- 22476575
TI  - Success rates of retinal detachment surgery: routine versus emergency setting.
AB  - BACKGROUND: Surgery for rhegmatogenous retinal detachment (RRD) should usually be
      performed as soon as possible. However, a risk of operating in an emergency
      setting has to be considered against the risk of delaying it. METHODS: In a
      retrospective, interventional, non-comparative clinical case series we reviewed
      the charts of all patients who underwent surgery for primary noncomplex RRD
      between February 1999 and July 2009. The primary anatomical success (PAS) of RRD
      surgery was the primary outcome measure, which was defined as permanent
      reattachment of the retina after a single surgical procedure. All cases were
      classified as (I) surgical cases, which were performed as emergency procedures
      the night of the patient's admission to the hospital (emergency setting), and as
      (II) those cases, which were operated in a routine setting during daytime
      (routine setting). Visual acuity was documented 2 and 6 months after surgery
      RESULTS: 1810 cases of primary noncomplex RRD were analysed. PAS rates were 88.0
      % in the routine setting and 87.3 % in the emergency setting (p = 0.67). While
      expert surgeons' PAS rates did not differ between routine and emergency, non
      experts achieved inferior anatomical results, when performing surgery in the
      emergency setting (81.6 % vs. 88.3 %; p = 0.02). There was no difference between
      expert (87.7 %) and non-expert surgeons (88.6 %) in the routine setting (p =
      0.75). There was no statistically significant difference in visual acuity.
      CONCLUSIONS: Prompt RRD surgery in an emergency setting did not improve the
      anatomical outcome and was worse if performed by non-expert surgeons. The
      possibility to schedule surgery may improve delivery of care without compromising
      the outcome. Although we did not see a significant functional difference, there
      was a trend for better visual acuity for experts and routine setting. If one
      decides that prompt surgery is necessary, it should only be done by an
      experienced vitreoretinal surgeon.

PMID- 22476576
TI  - Impaired fibrinolytic capacity and increased fibrin formation associate with
      myocardial infarction.
AB  - We assessed whether abnormality of haemostasis measured by a newly developed
      global method is associated with risk of a first myocardial infarction (MI). The
      global markers coagulation activation profile (Cp), fibrinolysis activation
      profile (Fp) and sum of fibrin optical density over time (Fibrin OD-sum) were
      determined in plasma from 800 MI cases and 1,123 controls included in the
      Stockholm Heart Epidemiology Program. Clot lysis time (CLT) was also determined
      based on raw data of fibrin OD from the global assay. Odds ratios (OR) of MI with
      95% confidence intervals (CI) were calculated using logistic regression. A Fp
      value <10th percentile value in controls was significantly associated with
      increased MI risk; OR after multivariate adjustments for conventional
      cardiovascular risk factors 1.66 (95% CI 1.22-2.27). For an abnormally long CLT
      (>90th percentile value in controls) the adjusted OR of MI was 2.62 (95% CI 1.87
      3.66) and for a high Fibrin OD-sum value (>90th percentile in controls) it was
      1.86 (95% CI 1.37-2.53). A high Cp value was not significantly associated with
      MI. In conclusion, we found that abnormal haemostasis in platelet-poor plasma,
      reflected either as an attenuated fibrinolytic capacity or the resulting increase
      of fibrin formation, was associated with increased MI risk.

PMID- 22476577
TI  - A collaborative environment for developing and validating predictive tools for
      protein biophysical characteristics.
AB  - The exchange of information between experimentalists and theoreticians is crucial
      to improving the predictive ability of theoretical methods and hence our
      understanding of the related biology. However many barriers exist which prevent
      the flow of information between the two disciplines. Enabling effective
      collaboration requires that experimentalists can easily apply computational tools
      to their data, share their data with theoreticians, and that both the
      experimental data and computational results are accessible to the wider
      community. We present a prototype collaborative environment for developing and
      validating predictive tools for protein biophysical characteristics. The
      environment is built on two central components; a new python-based integration
      module which allows theoreticians to provide and manage remote access to their
      programs; and PEATDB, a program for storing and sharing experimental data from
      protein biophysical characterisation studies. We demonstrate our approach by
      integrating PEATSA, a web-based service for predicting changes in protein
      biophysical characteristics, into PEATDB. Furthermore, we illustrate how the
      resulting environment aids method development using the Potapov dataset of
      experimentally measured DeltaDeltaGfold values, previously employed to validate
      and train protein stability prediction algorithms.

PMID- 22476578
TI  - Prediction of trypsin/molecular fragment binding affinities by free energy
      decomposition and empirical scores.
AB  - Two families of binding affinity estimation methodologies are described which
      were utilized in the SAMPL3 trypsin/fragment binding affinity challenge. The
      first is a free energy decomposition scheme based on a thermodynamic cycle, which
      included separate contributions from enthalpy and entropy of binding as well as a
      solvent contribution. Enthalpic contributions were estimated with PM6-DH2
      semiempirical quantum mechanical interaction energies, which were modified with a
      statistical error correction procedure. Entropic contributions were estimated
      with the rigid-rotor harmonic approximation, and solvent contributions to the
      free energy were estimated with several different methods. The second general
      methodology is the empirical score LISA, which contains several physics-based
      terms trained with the large PDBBind database of protein/ligand complexes. Here
      we also introduce LISA+, an updated version of LISA which, prior to scoring,
      classifies systems into one of four classes based on a ligand's hydrophobicity
      and molecular weight. Each version of the two methodologies (a total of 11
      methods) was trained against a compiled set of known trypsin binders available in
      the Protein Data Bank to yield scaling parameters for linear regression models.
      Both raw and scaled scores were submitted to SAMPL3. Variants of LISA showed
      relatively low absolute errors but also low correlation with experiment, while
      the free energy decomposition methods had modest success when scaling factors
      were included. Nonetheless, re-scaled LISA yielded the best predictions in the
      challenge in terms of RMS error, and six of these models placed in the top ten
      best predictions by RMS error. This work highlights some of the difficulties of
      predicting binding affinities of small molecular fragments to protein receptors
      as well as the benefit of using training data.

PMID- 22476579
TI  - Service utilization, expenditures, and success in a well-established system of
      care for young people with serious emotional disorders.
AB  - A major challenge in the implementation of systems of care is creating mechanisms
      to pay for services that are provided across social services systems and by
      multiple agencies. Using a managed care approach to coordinate service provision
      may be one way to effectively bridge the gap across agencies while also providing
      quality care. The authors explore the benefits of a managed care approach to
      service delivery within a well established system of care by describing the
      treatment planning process used by the system of care; describing the type and
      patterns of services provided to young people; and by describing the process used
      to bill for services. The authors also examine the impact of client and service
      characteristics on overall expenditures as well as the effect that patterns of
      service utilization and expenditures of care have on the likelihood that young
      people and their families will successfully meet their clinical objectives. 

PMID- 22476580
TI  - A novel dimerization interface of cyclic nucleotide binding domain, which is
      disrupted in presence of cAMP: implications for CNG channels gating.
AB  - Cyclic nucleotide binding domain (CNBD) is a ubiquitous domain of effector
      proteins involved in signalling cascades of prokaryota and eukaryota. CNBD
      activation by cyclic nucleotide monophosphate (cNMP) is studied well in the case
      of several proteins. However, this knowledge is hardly applicable to cNMP
      modulated cation channels. Despite the availability of CNBD crystal structures of
      bacterial cyclic nucleotide-gated (CNG) and mammalian hyperpolarization-activated
      cyclic nucleotide-modulated (HCN) channels in presence and absence of the cNMP,
      the full understanding of CNBD conformational changes during activation is
      lacking. Here, we describe a novel CNBD dimerization interface found in crystal
      structures of bacterial CNG channel MlotiK1 and mammalian cAMP-activated guanine
      nucleotide-exchange factor Epac2. Molecular dynamics simulations show that the
      found interface is stable on the studied timescale of 100 ns, in contrast to the
      dimerization interface, reported previously. Comparisons with cN-bound structures
      of CNBD show that the dimerization is incompatible with cAMP binding. Thus, the
      cAMP-dependent monomerization of CNBD may be an alternative mechanism of the cAMP
      sensing. Based on these findings, we propose a model of the bacterial CNG channel
      modulation by cAMP.

PMID- 22476581
TI  - Effect of environmental gradient in coastal vegetation on communities of
      arbuscular mycorrhizal fungi associated with Ixeris repens (Asteraceae).
AB  - The community structure of arbuscular mycorrhizal (AM) fungi associated with
      Ixeris repens was studied in coastal vegetation near the Tottori sand dunes in
      Japan. I. repens produces roots from a subterranean stem growing near the soil
      surface which provides an opportunity to examine the effects of an environmental
      gradient related to distance from the sea on AM fungal communities at a regular
      soil depth. Based on partial sequences of the nuclear large subunit ribosomal RNA
      gene, AM fungi in root samples were divided into 17 phylotypes. Among these, five
      AM fungal phylotypes in Glomus and Diversispora were dominant near the seaward
      forefront of the vegetation. Redundancy analysis of the AM fungal community
      showed significant relationships between the distribution of phylotypes and
      environmental variables such as distance from the sea, water-soluble sodium in
      soil, and some coexisting plant species. These results suggest that environmental
      gradients in the coastal vegetation can be determinants of the AM fungal
      community.

PMID- 22476582
TI  - Association of Pinus banksiana Lamb. and Populus tremuloides Michx. seedling fine
      roots with Sistotrema brinkmannii (Bres.) J. Erikss. (Basidiomycotina).
AB  - Sistotrema brinkmannii (Bres.) J. Erikss. (Basidiomycotina, Hydanaceae), commonly
      regarded as a wood decay fungus, was consistently isolated from bareroot nursery
      Pinus banksiana Lamb. seedlings. S. brinkmannii was found in ectomycorrhizae
      formed by Thelephora terrestris Ehrh., Laccaria laccata (Scop.) Cooke, and
      Suillus luteus (L.) Roussel. In pure culture combinations with sterile P.
      banksiana and Populus tremuloides Michx. seedlings, S. brinkmannii colonized root
      cortical cells while not killing seedlings. Colonization by S. brinkmannii
      appeared to be intracellular but typical endo- or ectomycorrhizae were not
      formed. The fungus did not decay roots, although it was shown to produce
      cellulase in enzyme tests. Results suggest a unique association between S.
      brinkmannii and seedling roots that is neither mycorrhizal nor detrimental; its
      exact function remains to be elucidated.

PMID- 22476583
TI  - Human platelet lysate is an alternative to fetal bovine serum for large-scale
      expansion of bone marrow-derived mesenchymal stromal cells.
AB  - Human platelet lysate (HPL) was evaluated as an alternative to fetal bovine serum
      (FBS) in large-scale culturing of bone marrow-derived mesenchymal stromal cells
      (BM-MSCs) for therapeutic applications. Dulbecco's modified Eagle medium (DMEM)of
      low glucose (LG) and Knock Out (KO) were used with human platelet lysate (HPL) as
      LG-HPL and KO-HPL, and with FBS as LG-FBS and KO-FBS to culture the BM-MSCs. HPL
      at 10 % (v/v) supported BM-MSCs growth and subsequent isolation efficiency
      generated >90 * 10(6) MSCs in LG-HPL. Population doublings (PDs) and population
      doubling times of LG-HPL and KO-HPL (PDT) were not significantly different but LG
      HPL showed a significant clonogenic potential and HPL cultures had an average PDT
      of 36.5 +/- 6.5 h and an average PDs of 5 +/- 0.7/passage. BM-MSCs cultured with
      LG-HPL had significantly higher immunosuppression compared to LG-FBS, but KO-HPL
      and KO-FBS-grown cultures were not significantly different. HPL is therefore
      alternative to FBS for large-scale production of BM-MSCs for therapeutic
      applications.

PMID- 22476585
TI  - Esophageal squamous cell carcinoma: assessing tumor angiogenesis using multi
      slice CT perfusion imaging.
AB  - OBJECTIVES: The purpose of this study was to investigate the correlation between
      multi-slice computed tomographic perfusion imaging (CTPI) parameters and
      immunohistologic markers of angiogenesis in esophageal squamous cell carcinoma
      (ESCC). METHODS: Fifty patients with histologically proven esophageal squamous
      cell carcinoma were enrolled in this study. All subjects underwent multi-slice CT
      perfusion scan. The hemodynamic parameters of vascular tumor, including blood
      volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface
      (PS) were generated. All the ESCC specimens were stained immunohistochemically to
      identify CD31 for quantification of microvessel density (MVD). CTPI parameters
      were correlated with MVD by using Pearson correlation analysis. RESULTS: The
      value of CT perfusion parameters of ESCC were as follows: BF 116.71 +/- 47.59
      ml/100 g/min, BV 6.74 +/- 2.70 ml/100 g, MTT 6.42 +/- 2.84 s, PS 13.82 +/- 6.25
      ml/100 g/min. The mean MVD of all 50 tumor specimens was 34.44 +/- 19.75. The PS
      values were significantly higher in ESCC patients with involvement of lymph node
      than those without involvement of lymph node (p < 0.01). Blood volume and
      permeability surface were positively correlated with MVD (p < 0.01), whereas no
      significant correlation was observed between MVD and BF or between MVD and MTT.
      CONCLUSIONS: Blood volume and permeability surface were positively correlated
      with MVD. CTPI could reflect the angiogenesis in ESCC.

PMID- 22476584
TI  - Glucose metabolism in fish: a review.
AB  - Teleost fishes represent a highly diverse group consisting of more than 20,000
      species living across all aquatic environments. This group has significant
      economical, societal and environmental impacts, yet research efforts have
      concentrated primarily on salmonid and cyprinid species. This review examines
      carbohydrate/glucose metabolism and its regulation in these model species
      including the role of hormones and diet. Over the past decade, molecular tools
      have been used to address some of the downstream components of these processes
      and these are incorporated to better understand the roles played by carbohydrates
      and their regulatory paths. Glucose metabolism remains a contentious area as many
      fish species are traditionally considered glucose intolerant and, therefore, one
      might expect that the use and storage of glucose would be considered of minor
      importance. However, the actual picture is not so clear since the apparent
      intolerance of fish to carbohydrates is not evident in herbivorous and omnivorous
      species and even in carnivorous species, glucose is important for specific
      tissues and/or for specific activities. Thus, our aim is to up-date carbohydrate
      metabolism in fish, placing it to the context of these new experimental tools and
      its relationship to dietary intake. Finally, we suggest that new research
      directions ultimately will lead to a better understanding of these processes.

PMID- 22476587
TI  - Protective effects of 3,4-oxo-isopropylidene-shikimic acid on experimental
      colitis induced by trinitrobenzenesulfonic acid in rats.
AB  - BACKGROUND: 3,4-Oxo-isopropylidene-shikimic acid (ISA) is a derivative of
      shikimic acid (SA). SA is extracted from Illicium verum Hook.fil., which has been
      used in traditional Chinese medicine and used for treating vomiting, stomach
      aches, insomnia, skin inflammation, and rheumatic pain. AIMS: To investigate the
      effects and the protective mechanism of 3,4-oxo-isopropylidene-shikimic acid on
      experimental colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS)
      in rats. METHODS: Colitis in rats was induced by colonic administration with
      TNBS. ISA (50, 100, and 200 mg/kg) was administered for 12 days to experimental
      colitis rats. The inflammatory degree was assessed by macroscopic damage score,
      colon weight/length ratios (mg/cm), and myeloperoxidase (MPO) activity.
      Malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) levels, and
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), inducible nitric
      oxide synthase (iNOS) activities were measured with biochemical methods. RESULTS:
      ISA significantly ameliorated macroscopic damage, reduced colon weight/length
      ratios and the activity of MPO, depressed MDA and NO levels and iNOS activity,
      and enhanced GSH level, and GSH-Px and SOD activities in the colon tissues of
      experimental colitis in a dose-dependent manner. Moreover, the effect of ISA (200
      mg/kg) was as effective as sulfasalazine (500 mg/kg). CONCLUSIONS: The findings
      of this study demonstrate the protective effect of ISA on experimental colitis,
      probably due to an antioxidant action.

PMID- 22476586
TI  - Advances in the current treatment of autoimmune hepatitis.
AB  - Current treatment strategies for autoimmune hepatitis are complicated by frequent
      relapse after drug withdrawal, medication intolerance, and refractory disease.
      The objective of this review is to describe advances that have improved treatment
      outcomes by defining the optimum objectives of initial therapy, managing relapse
      more effectively, identifying problematic patients early, and incorporating the
      new pharmacological interventions that have emerged as frontline and salvage
      therapies. Initial corticosteroid treatment should be continued until serum
      aminotransferase, gamma-globulin, and immunoglobulin G levels are normal, and
      maintenance of this improvement for 3-8 months before liver tissue assessment.
      Improvement to normal liver tissue is the ideal histological result that
      justifies drug withdrawal, but it is achievable in only 22 % of patients. Minimum
      portal hepatitis, inactive cirrhosis, or minimally active cirrhosis is the most
      common treatment end point. Relapse after drug withdrawal warrants institution of
      a long-term maintenance regimen, preferably with azathioprine. Mathematical
      models can identify problematic adult patients early, as also can clinical
      phenotype (age <= 30 years and HLA DRB1 03), rapidity of treatment response (<=
      24 months), presence of antibodies to soluble liver antigen, and non-white
      ethnicity. The calcineurin inhibitors (cyclosporine and tacrolimus) can be
      effective in steroid-refractory disease; mycophenolate mofetil can be
      corticosteroid-sparing and effective for azathioprine intolerance; budesonide
      combined with azathioprine can be effective for treatment-naive, non-cirrhotic
      patients. Standard treatment regimens for autoimmune hepatitis can be upgraded
      without adjustments that require major new expertise.

PMID- 22476588
TI  - Thymoquinone prevents and ameliorates dextran sulfate sodium-induced colitis in
      mice.
AB  - BACKGROUND: Thymoquinone (TQ), an active ingredient of the seed oil extract of
      Nigella sativa Linn, has previously been shown to possess antitumor, antioxidant,
      and anti-inflammatory bioactivity. Whether TQ has any effect on colitis remains
      controversial. AIM: The aim of this study was to determine whether treatment with
      TQ prevents and ameliorates colonic inflammation in a mouse model of inflammatory
      bowel disease. METHODS: C57BL/6 murine colitis was induced by the administration
      of dextran sodium sulfate (DSS) (3 % W/V) in the drinking water supplied to the
      mice for 7 consecutive days. The mice with colitis were treated with 5, 10, or 25
      mg/kg TQ orally, and changes in body weight and macroscopic and microscopic
      colitis scores were examined. In addition, biochemical analyses were conducted.
      RESULTS: The treatment of mice with TQ prevented and significantly reduced the
      appearance of diarrhea and body weight loss. These results were associated with
      amelioration of colitis-related damage, as measured by macroscopic and
      microscopic colitis scores. In addition, there was a significant reduction in
      colonic myeloperoxidase activity and malondialdehyde levels and an increase in
      glutathione levels. CONCLUSIONS: These results indicate that TQ administration
      can prevent and improve murine DSS-induced colitis. These findings suggest that
      TQ could serve as a potential therapeutic agent for the treatment of patients
      with inflammatory bowel disease.

PMID- 22476589
TI  - The origin of diversity: studying the evolution of multi-faceted CD8+ T cell
      responses.
AB  - During the past two decades of research in T cell biology, an increasing number
      of distinct T cell subsets arising during the transition from naive to antigen
      experienced T cells have been identified. Recently, it has been appreciated that,
      in different experimental settings, distinct T cell subsets can be generated in
      parallel within the same immune response. While signals driving a single
      "lineage" path of T cell differentiation are becoming increasingly clear, it
      remains largely enigmatic how the phenotypic and functional diversification
      creating a multi-faceted T cell response is achieved. Here, we review current
      literature indicating that diversification is a stable trait of CD8(+) T cell
      responses. We showcase novel technologies providing deeper insights into the
      process of diversification among the descendants of individual T cells, and
      introduce two models that emphasize either intrinsic noise or extrinsic signals
      as driving forces behind the diversification of single cell-derived T cell
      progeny populations in vivo.

PMID- 22476591
TI  - Editorial: Nuclear and radiation accidents.

PMID- 22476590
TI  - Paraspeckle nuclear bodies--useful uselessness?
AB  - The nucleus of higher eukaryotes, such as humans and mice, is compartmentalized
      into multiple nuclear bodies, an organization that allows for the regulation of
      complex gene expression pathways that are characteristic of these organisms.
      Paraspeckles are recently discovered, mammalian-specific nuclear bodies built on
      a long, non-protein-coding RNA, NEAT1 (nuclear-enriched abundant transcript 1),
      which assembles various protein components including RNA-binding proteins of the
      DBHS (Drosophila behavior and human splicing) family. Paraspeckles have been
      proposed to control several biological processes, such as stress responses and
      cellular differentiation, but their function at the whole animal level remains
      unclear. In this review, we summarize a series of studies on paraspeckles that
      have been carried out in the decade since their discovery and discuss their
      physiological function and molecular mechanism.

PMID- 22476592
TI  - Basic principles of molecular effects of irradiation.
AB  - In order to understand the consequences of radiation a thorough understanding of
      the radiobiological mechanisms of the molecular up to the clinical level is of
      importance. Radiobiology therefore combines the basic principles of physics as
      well as biology and medicine and is concerned with the action of radiation from
      the subcellular level up to the living organism. Topics of interest and relevance
      are covered in much more broadness as is possible in the short following article
      in the literature to which the interested reader is referred to. Classical books
      in this field were written by Steel et al. (1989) as well as by Hall (1994).
      Topics usually covered by radiobiological reviews are the classification of
      different types of radiation, cell cycle dependency of radiation effects, types
      of radiation damage and cell death, dose response curves, measurement of
      radiation damage, the oxygen effect, relative biological effectiveness, the
      influence of dose rate, and several other important research areas. This short
      overview will concentrate on a subset of radiobiological topics of high
      importance and relative novelty.

PMID- 22476593
TI  - Preparedness for radiological emergency situations in Austria.
AB  - This article presents the Austrian system of emergency preparedness for nuclear
      and radiological emergency situations. It demonstrates, in particular, the legal
      basis, the roles and competencies of the competent authorities, international and
      bilateral conventions on early notification of nuclear accidents, the Austrian
      emergency plans, the Austrian radiation monitoring system, the operated prognosis
      and decision support systems and the results of an estimation of possible impacts
      of nuclear power plant disasters on Austria.

PMID- 22476594
TI  - "Nuclear" medicine physicians as communicators: their point of view on the
      aftermath of "nuclear" disaster.
AB  - On March 11th, 2011 earthquakes and a subsequent tsunami devastated northern
      Japan. The consecutive technical catastrophe in the Fukushima Daiichi nuclear
      power plant was not only an additional local tragedy, it also turned out to be a
      global disaster. In this review we intend to discuss emerging problems and
      enlighten a way to communicate in such events, tell people how to react in such
      scenarios and prevent panic by providing rational information.

PMID- 22476595
TI  - Individualised PPI prescription in patients on combination antiplatelet therapy
      and upper gastrointestinal events after percutaneous coronary intervention: a
      cohort study.
AB  - BACKGROUND: We investigated the effect of individualised proton pump inhibitors
      (PPI) prescription on upper gastrointestinal adverse events in a cohort of
      patients who received combination antiplatelet therapy (aspirin and clopidogrel)
      after percutaneous coronary intervention (PCI). METHODS: Upper gastrointestinal
      risk factors and other parameters were extracted from a dedicated electronic
      database. Patients were contacted with a standardised questionnaire. A structured
      phone interview was performed in all patients with upper gastrointestinal adverse
      events. RESULTS: A cohort of 718 patients on combination therapy yielded 87
      (12.1%) patients with prophylactic PPI treatment. Upper gastrointestinal adverse
      events occurred in 18.4% patients with and in 11.1% patients without prophylactic
      PPI (OR 1.80, P = 0.054). Co-treatment with corticosteroids was the main
      identifiable risk factor for upper gastrointestinal adverse events (adjusted OR
      5.45, P = 0.014). CONCLUSIONS: Individualised prescription of PPI-prophylaxis
      after PCI in patients on combined antiplatelet therapy based on risk assessment
      for upper gastrointestinal bleeding seems to represent an effective measure to
      minimise upper gastrointestinal adverse events after PCI.

PMID- 22476596
TI  - [Prediction of the final degree in the 2002 reformed curriculum at the Medical
      University of Vienna].
AB  - In 2002 a reform curriculum was implemented at Medical University of Vienna. At
      the end of each study-year students have to pass a summative integrative
      examination consisting of single choice questions. We examined the study success
      of 674 students (50.8% of the cohort) who were surveyed at the beginning of their
      studies. The questionnaire used consisted of 67 items concerning the main success
      factors taken from the literature. Success was most predicted by schoolmarks,
      study-motivation ("keen to acquire knowledge"), the importance of study success,
      self-confidence to reach this goal, not too specific ideas about future
      employment, high learning capacity, and low test anxiety. Some aspects having
      predictive power for the first-year exam (sex, German mother tongue) showed no
      more impact on study success. Other aspects described to be predictive in
      retrospective studies could not be verified in this prospective study.

PMID- 22476598
TI  - Chlorophyllin for the control of Ichthyophthirius multifiliis (Fouquet).
AB  - Tests were conducted to determine the efficiency of the photodynamic substance
      chlorophyllin to kill different life stages of the protozoan parasite
      Ichthyophthirius mulftifiliis (Fouquet) which causes the white spot disease in
      many freshwater fish species. This study has developed a new treatment for the
      control of ichthyophthiriosis, and demonstrated that non-toxic water-soluble
      chlorophyll (chlorophyllin) is a potential remedial agent at low concentrations
      for this serious parasitic disease.

PMID- 22476599
TI  - Previous exposure to a low infectious dose of Leishmania major exacerbates
      infection with Leishmania infantum in the susceptible BALB/c mouse.
AB  - The geographic distribution of Leishmania major overlaps with several other
      species of Leishmania. This study seeks to examine what effect previous exposure
      to L. major has on the outcome of infection with Leishmania infantum, the agent
      of virulent visceral leishmaniasis. The L. major immune response is well
      characterized by a strong Th1 response leading to resolution and protection
      against subsequent re-infection. A contrasting Th2 immune response leads to
      disseminated disease, while the role Th17 cytokines may play in Leishmania
      infection is still being explored. The cytokine profile, antibody titer, and
      parasite burden were evaluated in the susceptible BALB/c mouse after L. infantum
      infection in either naive mice or those previously infected with a low/self
      healing dose of L. major. Only IL-4 expression in mice previously exposed to L.
      major was found to be significantly increased over controls, a cytokine with an
      ambiguous role in L. infantum infection. However, disease exacerbation, with a
      notably higher parasite burden, was observed in the L. major exposed mice
      compared to the L. infantum only. Cross-reactive antibodies were seen in both
      groups of infected mice regardless of their immune history. Studies have shown a
      role for opsonizing antibodies leading to increased disease in visceral
      leishmaniasis. We speculate that cross-reactive antibodies may be playing a role
      in augmenting visceral disease in mice with immunological memory to L. major.

PMID- 22476600
TI  - Adulticide effect of Monticalia greenmaniana (Asteraceae) against Lutzomyia
      migonei (Diptera: Psychodidae).
AB  - Leishmaniasis is a public health problem that has been increasing year by year,
      with the further difficulty that an efficient control system is not available.
      Therefore, it is necessary to search for less contaminating and dangerous
      alternatives for controlling Leishmania transmitting sandflies. The purpose of
      this study was to evaluate the activity of Monticalia greenmaniana (Asteraceae)
      extracts and essential oil as an adulticide against Lutzomyia migonei (Diptera:
      Psychodidae) females, from a laboratory colony, in experimental conditions. Dry
      aerial parts of M. greenmaniana (Hieron) Jeffrey were used. Methanolic and
      aqueous extracts were prepared, and essential oil was obtained by
      hydrodistillation. Adulticide tests in pots, adulticide tests in cages, and
      knocked-down effects were determined. The results obtained demonstrated that
      methanolic and aqueous extracts produced adulticide activity. The essential oil
      from M. greenmaniana was proved to be the most toxic against L. migonei, with a
      95 % death rate at a concentration of 0.01 mg/ml during a 1-h exposure. The
      essential oil showed a DL50 = 0.0050 and DL98 = 0.0066 mg/ml. The methanolic
      extract was DL50 = 0.130 and DL98 = 1.016 mg/ml, and the aqueous extract, DL50 =
      0.487 and DL98 10.924 mg/ml. The knocked-down effect for the M. greenmaniana oil
      showed a KDTL50 = 48.6 and KDTL98 = 90.1 min. It was concluded that the essential
      oil from M. greenmaniana showed a strong insecticide effect against L. migonei
      females, which encourages us to continue these studies in search for control
      alternatives against sandflies.

PMID- 22476601
TI  - Three novel myxobolid species of genera Henneguya and Myxobolus (Myxosporea:
      Bivalvulida) from marine fish in Japan.
AB  - Myxosporean genera Henneguya and Myxobolus (Bivalvulida: Myxobolidae) are closely
      related in morphology and molecular phylogeny, speciose with approximately 1,000
      nominal species. The majority of them are recorded from freshwater fish
      worldwide, and few are known from marine fish. In this study, three myxobolid
      spp. are described from marine fish around Japan. Two novel Henneguya spp.,
      Henneguya ogawai sp. n. and Henneguya yokoyamai sp. n., are described from two
      black sea breams (Acanthopagrus schlegelii) fished in the Inland Sea
      (Setonaikai), Japan. Plasmodia of the former species were localized in the
      esophageal or intestinal wall, and those of the latter species were in the wall
      of the gall bladder and peritoneum. Spore development in plasmodia of these two
      species was synchronous. The spore body of H. ogawai sp. n. was 11.0 (8.9-12.2)
      MUm in length, 6.9 (6.3-7.5) MUm in width, 5.9 (5.2-6.6) MUm in thickness, with a
      bifurcated caudal process of equal length, 10.0 (8.4-12.7) MUm long; total spore
      length, 21.1 (19.2-23.4) MUm. It contained two polar capsule, 4.3 (3.8-5.2) * 1.9
      (1.4-2.3) MUm. The spore body of H. yokoyamai sp. n. was 11.0 (10.1-13.7) MUm in
      length, 7.1 (6.6-7.5) MUm in width, and 5.6 (4.5-6.4) MUm in thickness, with a
      bifurcated caudal process of equal length, 14.1 (10.8-17.0) MUm long; total spore
      length, 25.0 (21.9-29.2) MUm. It contained two polar capsules, 3.7 (3.1-4.2) *
      2.0 (1.8-2.4) MUm. A novel Myxobolus sp., Myxobolus machidai sp. n., is described
      from a spotted knifejaw (Oplegnathus punctatus) fished in the Sea of Japan, off
      Shimonoseki, Yamaguchi Prefecture, Japan. Plasmodia were embedded in the
      esophageal wall. Its round spore was small in size, 9.0 (8.1-9.4) MUm in length,
      7.8 (7.5-8.3) MUm in width, and 5.5 (5.1-6.0) MUm in thickness. It contained two
      polar capsules, 3.5 (3.2-3.8) * 2.3 (2.2-2.5) MUm. Spore development in a
      plasmodium was asynchronous. Nucleotide sequencing of the small subunit ribosomal
      RNA gene (SSU rDNA) of these two novel Henneguya spp. revealed a close
      phylogenetic relationship with the marine clade of Henneguya spp.; however, they
      were distinct in morphology and SSU rDNA sequence from any known species. M.
      machidai sp. n. was grouped with freshwater Henneguya spp. in a phylogenetic tree
      based on the SSU rDNA, distant from a known marine clade of Myxobolus spp.
      reported mainly from the Mediterranean Sea. This is the first record of Henneguya
      Myxobolus spp. from natural marine water in Japan.

PMID- 22476602
TI  - In vitro activity of extracts and isolated polyphenols from West African
      medicinal plants against Plasmodium falciparum.
AB  - The aim of the study was to screen 11 selected traditional medicinal plants from
      West Africa for their in vitro antiplasmodial activity in order to determine the
      activity of single and of combination of plant extracts and to examine the
      activity of isolated pure compounds. Ethanolic and aqueous extracts of the 11
      selected plants and pure compounds from Phyllanthus muellerianus and Anogeissus
      leiocarpus were tested in vitro against Plasmodium falciparum 3D7. Proliferation
      inhibitory effects were monitored after 48 h. Among the plants and pure compounds
      investigated in this study, geraniin from P. muellerianus, ellagic, gentisic, and
      gallic acids from A. leiocarpus, and extracts from A. leiocarpus, P. muellerianus
      and combination of A. leiocarpus with P. muellerianus affected the proliferation
      of P. falciparum most potently. Significant inhibitory activity was observed in
      combination of A. leiocarpus with P. muellerianus (IC(50) = 10.8 MUg/ml), in
      combination of A. leiocarpus with Khaya senegalensis (IC(50) = 12.5 MUg/ml),
      ellagic acid (IC(50) = 2.88 MUM), and geraniin (IC(50) = 11.74 MUM). In general
      growth inhibition was concentration-dependent revealing IC(50) values ranging
      between 10.8 and -40.1 MUg/ml and 2.88 and 11.74 MUM for plant extracts and pure
      substances respectively. Comparison with literature sources of in vivo and in
      vitro toxicity data revealed that thresholds are up to two times higher than the
      determined IC(50) values. Thus, the present study suggests that geraniin from P.
      muellerianus; ellagic acid, gallic acid, and gentisic acid from A. leiocarpus;
      and combination of extracts from A. leiocarpus with either P. muellerianus or K.
      senegalensis could be a potential option for malaria treatment.

PMID- 22476604
TI  - Stenting right ventricular outflow in an infant with tetralogy of Fallot and well
      developed pulmonary arteries.
AB  - A right ventricular outflow tract stent was implanted in a 1-month-old (3.5 kg)
      baby boy with tetralogy of Fallot and worsening cyanosis to relieve infundibular
      and pulmonary valve stenosis in the setting of well-developed pulmonary artery
      branches. This management allowed a symmetric and optimal growth of the pulmonary
      artery branches, with right and left pulmonary arteries measuring 7-mm (z-score,
      +1.3 SD) and 7.3-mm (z-score, +1.7 SD), respectively, 3 months after stent
      implantation. No signs of pulmonary overcirculation developed, and complete
      surgical repair was performed at the age of 6 months.

PMID- 22476603
TI  - Molecular identification of Hartmannella vermiformis and Vannella persistens from
      man-made recreational water environments, Tehran, Iran.
AB  - A survey was conducted on man-made recreational water located in different
      regions of Tehran, Iran to detect the free-living amoebae present in ponds and
      fountains of parks and squares. Fifty water samples from 22 municipal districts
      of Tehran were screened for free-living amoebae and identified by morphological
      characters and polymerase chain reaction amplification. Amoebae detected were
      identified as Hartmannella vermiformis (12 %) and Vannella persistens (4 %),
      which are the first reports of these two amoebas in recreational water
      environments of Iran. Since, H. vermiformis, which is highly similar to strains
      serving as hosts for Legionella pneumophila, is a common component of the
      microbial community in fresh surface water. Although Vannella spp. is not proved
      to be pathogenic itself, they are capable of harboring pathogenic intracellular
      organisms. Due to some reports related to pathogenicity of these amoebas, the
      particular hazard related to these microorganisms should be taken into account in
      the encounter with drinking and washing in these waters. We recommend control
      strategies based on physical removal rather than on disinfection to be adopted
      where necessary.

PMID- 22476605
TI  - The Ross classification for heart failure in children after 25 years: a review
      and an age-stratified revision.
AB  - Accurate grading of the presence and severity of heart failure (HF) signs and
      symptoms in infants and children remains challenging. It has been 25 years since
      the Ross classification was first used for this purpose. Since then, several
      modifications of the system have been used and others proposed. New evidence has
      shown that in addition to signs and symptoms, data from echocardiography,
      exercise testing, and biomarkers such as N-terminal pro-brain natriuretic peptide
      (NT-proBNP) all are useful in stratifying outcomes for children with HF. It also
      is apparent that grading of signs and symptoms in children is dependent on age
      because infants manifest HF differently than toddlers and older children. This
      review culminates in a proposed new age-based Ross classification for HF in
      children that incorporates the most useful data from the last two decades.
      Testing of this new system will be important to determine whether an age
      stratified scoring system can unify the way communication of HF severity and
      research on HF in children is performed in the future.

PMID- 22476606
TI  - 2011 Riley Heart Center Symposium on cardiac development: development of the
      cardiac conduction system and arrhythmias.
AB  - This article gives an overview of the 2011 Riley Heart Center Symposium that was
      held in Indianapolis, IN, USA, 11-13 September, 2011.

PMID- 22476607
TI  - Intervention characteristics that facilitate return to work after sickness
      absence: a systematic literature review.
AB  - INTRODUCTION: In many Western countries, a vast amount of interventions exist
      that aim to facilitate return to work (RTW) after sickness absence. These
      interventions are usually focused on specific target populations such as
      employees with low back pain, stress-related complaints or adjustment disorders.
      The aim of the present study is to detect and identify characteristics of RTW
      interventions that generally facilitate return to work (i.e. in multiple target
      populations and across interventions). This type of knowledge is highly relevant
      to policy makers and health practitioners who want to deliver evidence based care
      that supports the employee's health and participation in labour. METHODS: We
      performed a keyword search (systematic literature review) in seven databases
      (period: 1994-2010). In total, 23 articles were included and assessed for their
      methodological quality. The characteristics of the interventions were evaluated
      as well. RESULTS: Early interventions, initiated in the first 6 weeks of the RTW
      process were scarce. These were effective to support RTW though.
      Multidisciplinary interventions appeared effective to support RTW in multiple
      target groups (e.g. back pain and adjustment disorders). Time contingent
      interventions in which activities followed a pre-defined schedule were effective
      in all physical complaints studied in this review. Activating interventions such
      as gradual RTW were effective in physical complaints. They have not been studied
      for people with psychological complaints. CONCLUSIONS: Early- and
      multidisciplinary intervention and time-contingent-, activating interventions
      appear most effective to support RTW.

PMID- 22476608
TI  - FABP4 is a candidate marker of cerebellar liponeurocytomas.
AB  - Cerebellar liponeurocytoma (cLPN) is a very rare central nervous system (CNS)
      tumour recently recognized as a clinical and pathological entity distinct from
      medulloblastoma (MB), and included in the WHO classification of CNS tumours under
      the heading "glioneuronal tumours". cLPN typically develop in adult age and have
      a favourable prognosis compared with MB. In this work, we reviewed the clinical
      and neuroradiological data of two novel cases of adult cLPN diagnosed at our
      institution; one patient developed distant metastases. We tried to identify novel
      molecular markers for this malignancy. We found that the transcription factor
      NEUROG1 (but not ATOH1) is expressed in cLPN, unlike normal adult cerebellum, and
      that fatty acid binding protein 4 (FABP4), typically found in adipocytes, is
      significantly overexpressed compared with both normal adult cerebellum and human
      MB. These findings suggest cLPN occur as a result of transformation of cerebellar
      progenitors, which are distinct from cerebellar granule progenitors, and
      aberrantly differentiate into adipocyte-like tumour cells. They also suggest that
      analysis of FABP4 expression is of help to differentiate cLPN from MB.

PMID- 22476609
TI  - An early attentional bias to BEGIN-stimuli of the smoking ritual is accompanied
      with mesocorticolimbic deactivations in smokers.
AB  - RATIONALE: Biased processing of drug-associated stimuli is believed to be a
      crucial feature of addiction. Particularly, an attentional bias seems to
      contribute to the disorder's maintenance. Recent studies suggest differential
      effects for stimuli associated with the beginning (BEGIN-smoking-stimuli) or the
      terminal stage of the smoking ritual (END-smoking-stimuli), with the former but
      not the later evoking high cue-reactivity. OBJECTIVE: The current study
      investigated the neuronal network underlying an attentional bias to BEGIN-smoking
      stimuli and END-smoking-stimuli in smokers and tested the hypothesis that the
      attentional bias is greater for BEGIN-smoking-stimuli. METHODS: Sixteen non
      deprived smokers and 16 non-smoking controls participated in an fMRI study. Drug
      pictures (BEGIN-smoking-stimuli, END-smoking-stimuli) and control pictures were
      overlaid with geometrical figures and presented for 300 ms. Subjects had to
      identify picture content (identification-task) or figure orientation (distraction
      task). The distraction-task was intended to demonstrate attentional bias.
      RESULTS: Behavioral data revealed an attentional bias to BEGIN-smoking-stimuli
      but not to END-smoking-stimuli in both groups. However, only smokers showed
      mesocorticolimbic deactivations in the distraction-task with BEGIN-smoking
      stimuli. Importantly, these deactivations were significantly stronger for BEGIN-
      than for END-smoking-stimuli and correlated with the attentional bias score.
      CONCLUSIONS: Several explanations may account for missing group differences in
      behavioral data. Brain data suggest smokers using regulatory strategies in
      response to BEGIN-smoking-stimuli to prevent the elicitation of motivational
      responses interfering with distraction-task performance. These strategies could
      be reflected in the observed deactivations and might lead to a performance level
      in smokers that is similar to that of non-smokers.

PMID- 22476610
TI  - Impact of varenicline on cue-specific craving assessed in the natural environment
      among treatment-seeking smokers.
AB  - RATIONALE: Varenicline is believed to work, in part, by reducing craving
      responses to smoking cues and by reducing general levels of craving; however,
      these hypotheses have never been evaluated with craving assessed in the natural
      environments of treatment-seeking smokers. OBJECTIVES: Ecological momentary
      assessment procedures were used to assess the impact of varenicline on cue
      specific and general craving in treatment-seeking smokers prior to quitting.
      METHODS: For 5 weeks prior to quitting, 60 smokers carried personal digital
      assistants that assessed their response to smoking or neutral cues. During week 1
      (baseline), participants did not receive medication; during weeks 2-4 (drug
      manipulation), participants were randomized to receive varenicline or placebo;
      during week 5 (standard therapy), all participants received varenicline. Craving
      was assessed before each cue; cue-specific craving and attention to cue were
      assessed after each cue. RESULTS: During all phases, smoking cues elicited
      greater craving than neutral cues; the magnitude of this effect declined after
      the first week. General craving declined across each phase of the study. Relative
      to the placebo condition, varenicline was associated with a greater decline in
      general craving over the drug manipulation phase. Varenicline did not
      significantly attenuate cue-specific craving during any phase of the study.
      CONCLUSIONS: Smoking cues delivered in the natural environment elicited strong
      craving responses in treatment-seeking smokers, but cue-specific craving was not
      affected by varenicline administered prior to the quit attempt. These findings
      suggest that the clinical efficacy of varenicline is not mediated by changes in
      cue-specific craving during the pre-quit period of treatment-seeking smokers.

PMID- 22476611
TI  - Assessment of response shift using two structural equation modeling techniques.
AB  - OBJECTIVE: To identify response shift using two structural equation modeling
      (SEM) techniques. STUDY DESIGN AND SETTING: Hypertensive patients (n = 909) with
      coronary artery disease (CAD) completed SF-36 surveys at both baseline and 1-year
      follow-up. Response shift was identified using Oort and Schmitt SEM techniques.
      The type of response shift linked to changes in various parameters of the SEM
      measurement model is defined differently for both SEM approaches. Effect sizes
      were calculated for the impact of response shift on the change of SF-36 domain
      scores when using the Oort approach. RESULTS: Both Oort and Schmitt SEM
      approaches identified response shift only in the SF-36 physical functioning (PF)
      scale. The effect size of recalibration on the change of PF domain scores when
      using the Oort approach was -0.12. CONCLUSION: This study showed that
      hypertensive patients with CAD experienced a response shift over a 1-year period.
      Both the SEM approaches identified response shift (uniform recalibration using
      the Oort approach and recalibration using the Schmitt approach); however, both
      approaches use different parameters to define and test response shift. We found
      that either the variation in analytic methods or the sample used may influence
      the identification and type of response shift.

PMID- 22476612
TI  - Clinical use of multifocal visual-evoked potentials in a glaucoma practice: a
      prospective study.
AB  - PURPOSE: To test a framework that describes how the multifocal visual-evoked
      potential (mfVEP) technique is used in a particular glaucoma practice. METHODS:
      In this prospective, descriptive study, glaucoma suspects, ocular hypertensives
      and glaucoma patients were referred for mfVEP testing by a single glaucoma
      specialist over a 2-year period. All patients underwent standard automated
      perimetry (SAP) and mfVEP testing within 3 months. Two hundred and ten patients
      (420 eyes) were referred for mfVEP testing for the following reasons: (1) normal
      SAP tests suspected of early functional loss (ocular hypertensives, n = 43; and
      glaucoma suspects on the basis of suspicious optic disks, n = 52); (2) normal
      tension glaucoma patients with suspected central SAP defects (n = 33); and (3)
      SAP abnormalities needing confirmation (n = 82). RESULTS: All the glaucoma
      suspects with normal SAP and mfVEP results remained untreated. Of those with
      abnormal mfVEP results, 68 % (15/22) were treated because the abnormal regions on
      the mfVEP were consistent with the abnormal regions seen during clinical
      examination of the optic disk. The mfVEP was abnormal in 86 % (69/80) of eyes
      with glaucomatous optic neuropathy and SAP damage, even though it did not result
      in an altered treatment regimen. In NTG patients, the mfVEP showed central
      defects in 44 % (12 of 27) of the eyes with apparently normal central fields and
      confirmed central scotomata in 92 % (36 of 39), leading to more rigorous
      surveillance of these patients. CONCLUSIONS: In a clinical practice, the mfVEP
      was used when clinical examination and subjective visual fields provided
      insufficient or conflicting information. This information influenced clinical
      management.

PMID- 22476613
TI  - The antidepressant effect of secoisolariciresinol, a lignan-type phytoestrogen
      constituent of flaxseed, on ovariectomized mice.
AB  - Secoisolariciresinol (SECO) is a natural lignan-type phytoestrogen constituent
      mainly found in flaxseed. It can be metabolized in vivo to mammalian lignans of
      enterodiol and enterolactone, which have been proven to be effective in relieving
      menopausal syndrome. Depression is one of the most common symptoms of menopausal
      syndrome, and is currently treated with estrogen replacement and antidepressant
      therapy. However, due to the serious side-effects of such agents, there are
      urgent needs for safer and more tolerable treatments. In this paper, using two
      classical depression models, the forced swimming test and the tail suspension
      test, we report the antidepressant effect of SECO on ovariectomized (OVX) mice by
      intragastric administration for 14 consecutive days at doses of 5, 10 and 20
      mg/kg. The results showed that SECO (10 mg/kg) treatment could significantly
      reduce the duration of immobility of OVX mice in these two models compared with
      the control group (OVX mice + vehicle), which was similar to the positive control
      imipramine. In addition, SECO treatment could substantially increase brain
      monoamine (norepinephrine and dopamine) levels in OVX mice. The present studies
      showed that SECO can reverse depressive-like behavior and exhibit monoamine
      enhancing effects.

PMID- 22476615
TI  - Diabetes and the heart-at the edge between upcoming solutions and newly detected
      problems.

PMID- 22476614
TI  - Coupled left-shift of Nav channels: modeling the Na+-loading and dysfunctional
      excitability of damaged axons.
AB  - Injury to neural tissue renders voltage-gated Na+ (Nav) channels leaky. Even mild
      axonal trauma initiates Na+-loading, leading to secondary Ca2+-loading and white
      matter degeneration. The nodal isoform is Nav1.6 and for Nav1.6-expressing HEK
      cells, traumatic whole cell stretch causes an immediate tetrodotoxin-sensitive
      Na+-leak. In stretch-damaged oocyte patches, Nav1.6 current undergoes damage
      intensity dependent hyperpolarizing- (left-) shifts, but whether left-shift
      underlies injured-axon Nav-leak is uncertain. Nav1.6 inactivation (availability)
      is kinetically limited by (coupled to) Nav activation, yielding coupled left
      shift (CLS) of the two processes: CLS should move the steady-state Nav1.6 "window
      conductance" closer to typical firing thresholds. Here we simulated excitability
      and ion homeostasis in free-running nodes of Ranvier to assess if hallmark
      injured-axon behaviors--Na+-loading, ectopic excitation, propagation block--would
      occur with Nav-CLS. Intact/traumatized axolemma ratios were varied, and for some
      simulations Na/K pumps were included, with varied in/outside volumes. We
      simulated saltatory propagation with one mid-axon node variously traumatized.
      While dissipating the [Na+] gradient and hyperactivating the Na/K pump, Nav-CLS
      generated neuropathic pain-like ectopic bursts. Depending on CLS magnitude,
      fraction of Nav channels affected, and pump intensity, tonic or burst firing or
      nodal inexcitability occurred, with [Na+] and [K+] fluctuating. Severe CLS
      induced inexcitability did not preclude Na+-loading; in fact, the steady-state
      Na+-leaks elicited large pump currents. At a mid-axon node, mild CLS perturbed
      normal anterograde propagation, and severe CLS blocked saltatory propagation.
      These results suggest that in damaged excitable cells, Nav-CLS could initiate
      cellular deterioration with attendant hyper- or hypo-excitability. Healthy-cell
      versions of Nav-CLS, however, could contribute to physiological rhythmic firing.

PMID- 22476616
TI  - [Comorbidity, hypoglycaemia and appropriate selection of antidiabetic
      pharmacotherapy in diabetic patients with heart failure in clinical practice in
      Germany. Results of the DiaRegis registry].
AB  - BACKGROUND: Patients with type 2 diabetes and heart failure are considered to be
      at high risk for hypoglycaemic complications. There is a considerable uncertainty
      with respect to the appropriate choice of antidiabetic pharmacotherapy in
      patients with type 2 diabetes and comorbid heart failure. Little is known about
      comorbidity, hypoglycaemia rates and selected pharmacotherapy in diabetic
      patients with heart failure in clinical practice. METHODS: DiaRegis is a
      prospective registry in Germany including 3,810 patients with type 2 diabetes
      receiving antidiabetic treatment with oral mono or oral dual combination therapy
      in 2009/2010. Only patients for which adjustment of pharmacotherapy (including
      the introduction of insulin and GLP-1 analogues) was deemed necessary were
      enrolled. We examined the differences in comorbidity, hypoglycaemia and choice of
      anti-diabetic pharmacotherapy between diabetics with and without clinical heart
      failure in clinical practice in Germany. RESULTS: For 3,746 patients, data on the
      presence of heart failure were available, median (IQR) age 65.9 (57.6-72.8) years
      and 46.8% were female. Patients with heart failure (n = 370; 9.9%) were older,
      had a higher BMI, were less physically active, and had more cardiovascular risk
      factors and a substantial comorbidity. Glycaemic control was comparable between
      groups. Of the patients with heart failure, 76.8% received metformin, 32.7%
      sulfonylureas, 2.2% glucosidase inhibitors, 4.3% glinides, 6.2% glitazones and
      7.3% DPP-4 inhibitors at baseline before adjustment of therapy. In multivariate
      analyses, patients with heart failure received less metformin (odds ratio (OR)
      0.58, 95% confidence interval (CI) 0.43-0.79) and sulfonylureas (OR 0.70, 95%CI
      0.52-0.95) but not thiazolidinediones (OR 1.22, 95%CI 0.82-1.81) or other
      antidiabetic drugs. Hypoglycaemia was considerably more frequent in diabetic
      patients with heart failure than in those without (OR 1.96, 95%CI 1.47-2.61).
      CONCLUSION: Patients with type 2 diabetes and heart failure had a substantially
      increased comorbidity burden compared to patients without heart failure. They
      more often suffered from episodes of hypoglycaemia, especially those requiring
      medical assistance. The diagnosis of heart failure did not impact the choice of
      antidiabetic pharmacotherapy in patients with type 2 diabetes. There was no
      differential use of thiazolidinediones despite evidence discouraging their use in
      patients with heart failure.

PMID- 22476617
TI  - Hepatic and adipocyte cells respond differentially to iron overload, hypoxic and
      inflammatory challenge.
AB  - Adipose tissue secretes numerous pro-inflammatory cytokines, such as interleukin
      (IL)-6 and tumor necrosis factor (TNF)-alpha that can lead to insulin resistance
      (IR). In the liver, both IL-6 and TNF-alpha induce IR by inhibiting
      phosphorylation or ubiquitination of IRS1. In IR development, Fe is a risk factor
      in type-2 diabetes development. We studied the expression of genes related to
      inflammation, hypoxia, and mitochondrial function in hepatic (HepG2) and adipose
      (3T3-L1) cells. HepG2 and 3T3-L1 cells were incubated with 20 MUM Fe, 40 MUM Fe,
      or 40 MUM Fe/20 mM glucose for 7 days and then challenged with 20 ng/ml IL-6
      and/or 100 MUM CoCl(2) for 20 h. We measured intracellular Fe levels and the
      relative expression of hepcidin, NF-kappaB, IL-6, TNF-alpha, hypoxia inducible
      factor 1alpha (HIF-1alpha), and mitofusin 2 (Mfn-2) mRNA using qRT-PCR. The
      intracellular Fe concentration in HepG2 cells did not change with 20 or 40 MUM
      Fe. However, levels were decreased with Fe/glucose and IL-6 and/or CoCl(2). 3T3
      L1 cells showed an increase in intracellular Fe with high Fe plus either IL-6 or
      CoCl(2). HepG2 cells incubated with 40 MUM Fe alone or Fe/glucose and challenged
      with IL-6 and/or CoCl(2) showed increased IL-6, NF-kappaB, and TNF-alpha mRNA
      expression and decreased mRNA expression of Mfn-2 in all experimental conditions.
      3T3-L1 cells incubated with 40 MUM Fe alone or Fe/glucose and challenged with IL
      6 showed increased NF-kappaB mRNA expression and decreased Mfn-2 expression in
      all experimental conditions. Thus, high Fe, inflammation, and hypoxia trigger the
      expression of genes related to inflammation and Fe metabolism in HepG2 cells, in
      3T3-L1 cells the same stimuli increased NF-kB and hepcidin expression.

PMID- 22476618
TI  - Increased plasma levels of granzymes in adult patients with chronic immune
      thrombocytopenia.

PMID- 22476619
TI  - Genomic associations for drought tolerance on the short arm of wheat chromosome
      4B.
AB  - Drought is a major constraint to maintaining yield stability of wheat in rain fed
      and limited irrigation agro-ecosystems. Genetic improvement for drought tolerance
      in wheat has been difficult due to quantitative nature of the trait involving
      multiple genes with variable effects and lack of effective selection strategies
      employing molecular markers. Here, a framework molecular linkage map was
      constructed using 173 DNA markers randomly distributed over the 21 wheat
      chromosomes. Grain yield and other drought-responsive shoot and root traits were
      phenotyped for 2 years under drought stress and well-watered conditions on a
      mapping population of recombinant inbred lines (RILs) derived from a cross
      between drought-sensitive semidwarf variety "WL711" and drought-tolerant
      traditional variety "C306". Thirty-seven genomics region were identified for 10
      drought-related traits at 18 different chromosomal locations but most of these
      showed small inconsistent effects. A consistent genomic region associated with
      drought susceptibility index (qDSI.4B.1) was mapped on the short arm of
      chromosome 4B, which also controlled grain yield per plant, harvest index, and
      root biomass under drought. Transcriptome profiling of the parents and two RIL
      bulks with extreme phenotypes revealed five genes underlying this genomic region
      that were differentially expressed between the parents as well as the two RIL
      bulks, suggesting that they are likely candidates for drought tolerance. Syntenic
      genomic regions of barley, rice, sorghum, and maize genomes were identified that
      also harbor genes for drought tolerance. Markers tightly linked to this genomic
      region in combination with other important regions on group 7 chromosomes may be
      used in marker-assisted breeding for drought tolerance in wheat.

PMID- 22476620
TI  - Unusual imaging features of completely isolated enteric duplication in a child.
AB  - We report a case of completely isolated enteric duplication in an 18-month-old
      boy in whom US revealed a reniform abdominal mass with a pseudokidney sign that
      had no connection to adjacent organs. Distinctive histopathological changes of
      the duplication account for these unusual imaging features. Our case represents a
      diagnostic challenge in this rare entity. To our knowledge, this is a unique
      case.

PMID- 22476622
TI  - Increased risk of stroke in oral contraceptive users carried replicated genetic
      variants: a population-based case-control study in China.
AB  - Combined oral contraceptives (COC) use is a unique risk factor for stroke in
      women, and may modify the associations between genetic polymorphisms and stroke.
      To investigate whether the genetic variants identified in a recent genome-wide
      association study (GWAS) could be replicated in Chinese women, as well as,
      whether related risk was different in COC users, 451 stroke cases and 831 age-
      and region-matched controls were recruited from our cohort. Genotyping of 3 SNPs
      (rs700651, rs10958409, and rs1333040) was performed by the polymerase chain
      reaction assay with TaqMan probes. The history of contraceptive use and relevant
      information were obtained from a face-to-face interview. Odds ratios (OR) with 95
      % confidence interval (CI) were estimated under conditional logistic regression
      model after adjustment for cardiovascular covariates. Our study replicated the
      associations of rs10958409 and rs1333040, with the risk of stroke, especially
      hemorrhagic subtype, but failed to confirm association of rs700651. COC use was
      associated with a 1.56-fold (OR 1.56, 95 % CI 1.21-2.01) increased risk of
      stroke. COC users with rs10958409 GA/AA or rs1333040 CT/TT genotypes had an
      increased risk of overall stroke by 1.59-fold (OR 2.59, 95 % CI 1.59-4.19) and
      3.24-fold (OR 4.24, 95 % CI 1.71-10.49), respectively, compared with the non
      users with wild-type genotypes. Moreover, the risk of hemorrhagic stroke
      increased by 4.81- and 15.06-fold when risk allele carriers of rs10958409 or
      rs1333040 who took COC. Our results confirmed the associations of two GWAS SNPs,
      also suggested combination effects of these genetic variants and COC use on
      stroke risk.

PMID- 22476621
TI  - Fresh and cryopreserved amniotic membrane secrete the trefoil factor family
      peptide 3 that is well known to promote wound healing.
AB  - Amniotic membrane (AM) is often used for the treatment of ocular surface
      ulcerations and other corneal defects. Trefoil factor family (TFF) peptide 3 is
      produced by conjunctival goblet cells, participates in tear film physiology and
      has also been shown to be involved in ocular surface restitution after corneal
      injury. In the present study, we questioned whether AM also might be a source of
      TFF3 and if yes whether the secretion rate of TFF3 is changed by proinflammatory
      cytokines or by cryoconservation of AM. By means of RT-PCR, the mRNA expression
      of all three known TFF peptides could be detected in AM. Immunohistochemistry on
      paraffin-embedded sections localized TFF3 protein and also TFF2 in AM cells and
      Western blot analysis revealed TFF3 protein in AM. Stimulation experiments with
      proinflammatory cytokines and subsequent TFF3 ELISA measurements revealed that
      the secretion rate of fresh or cryoconserved AM was not significantly changed.
      The results indicate that TFF peptides are produced by AM. TFF3 may contribute to
      ocular surface wound healing after AM transplantation, but its production by AM
      is not further inducible by proinflammatory stimuli. Cryopreservation has no
      effect on the secretion rate of TFF3 supporting the use of cryopreserved AM for
      transplantation.

PMID- 22476623
TI  - Further clarification of the contribution of the ADH1C gene to vulnerability of
      alcoholism and selected liver diseases.
AB  - The alcohol dehydrogenase 1C (ADH1C) subunit is an important member of the
      alcohol dehydrogenase family, a set of genes that plays a major role in the
      catabolism of ethanol. Numerous association studies have provided compelling
      evidence that ADH1C gene variation (formerly ADH3) is associated with altered
      genetic susceptibility to alcoholism and alcohol-related liver disease,
      cirrhosis, or pancreatitis. However, the results have been inconsistent,
      partially, because each study involved a limited number of subjects, and some
      were underpowered. Using cumulative data over the past two decades, this meta
      analysis (6,796 cases and 6,938 controls) considered samples of Asian, European,
      African, and Native American origins to examine whether the aggregate genotype
      provide statistically significant evidence of association. The results showed
      strong evidence of association between ADH1C Ile350Val (rs698, formerly ADH1C
      *1/*2) and alcohol dependence (AD) and abuse in the combined studies. The overall
      allelic (Val vs. Ile or *2 vs. *1) P value was 1 * 10(-8) and odds ratio (OR) was
      1.51 (1.31, 1.73). The Asian populations produced stronger evidence of
      association with an allelic P value of 4 * 10(-33) [OR 2.14 (1.89, 2.43)] with no
      evidence of heterogeneity, and the dominant and recessive models revealed even
      stronger effect sizes. The strong evidence remained when stricter criteria and
      sub-group analyses were applied, while Asians always showed stronger associations
      than other populations. Our findings support that ADH1C Ile may lower the risk of
      AD and alcohol abuse as well as alcohol-related cirrhosis in pooled populations,
      with the strongest and most consistent effects in Asians.

PMID- 22476624
TI  - Genomic rearrangements at the FRA2H common fragile site frequently involve non
      homologous recombination events across LTR and L1(LINE) repeats.
AB  - Common fragile sites (cFSs) are non-random chromosomal regions that are prone to
      breakage under conditions of replication stress. DNA damage and chromosomal
      alterations at cFSs appear to be critical events in the development of various
      human diseases, especially carcinogenesis. Despite the growing interest in
      understanding the nature of cFS instability, only a few cFSs have been
      molecularly characterised. In this study, we fine-mapped the location of FRA2H
      using six-colour fluorescence in situ hybridisation and showed that it is one of
      the most active cFSs in the human genome. FRA2H encompasses approximately 530 kb
      of a gene-poor region containing a novel large intergenic non-coding RNA gene
      (AC097500.2). Using custom-designed array comparative genomic hybridisation, we
      detected gross and submicroscopic chromosomal rearrangements involving FRA2H in a
      panel of 54 neuroblastoma, colon and breast cancer cell lines. The genomic
      alterations frequently involved different classes of long terminal repeats and
      long interspersed nuclear elements. An analysis of breakpoint junction sequence
      motifs predominantly revealed signatures of microhomology-mediated non-homologous
      recombination events. Our data provide insight into the molecular structure of
      cFSs and sequence motifs affected by their activation in cancer. Identifying cFS
      sequences will accelerate the search for DNA biomarkers and targets for
      individualised therapies.

PMID- 22476626
TI  - Prevalence of posterior vitreous detachment in the population with type II
      diabetes mellitus and its effect on diabetic retinopathy: Sankara Nethralaya
      Diabetic Retinopathy Epidemiology and Molecular Genetic Study SN-DREAMS report
      no. 23.
AB  - OBJECTIVE: To report the prevalence of posterior vitreous detachment (PVD), and
      predisposing factors to PVD and their effect on diabetic retinopathy. STUDY
      DESIGN: Population-based study. METHODS: The study included subjects with type II
      diabetes mellitus enrolled from a cross-sectional study. Participants underwent a
      biochemical examination, and a comprehensive ocular examination which included
      stereo fundus photography. Diabetic retinopathy was graded by use of Klein's
      classification and diabetic maculopathy was graded by use of the Early Treatment
      Diabetic Retinopathy Study (ETDRS) criteria. The status of the posterior vitreous
      was assessed by use of B-scan ultrasonography. RESULTS: The prevalence of PVD was
      63.3 %. The risk factors for PVD included age, gender, sight-threatening diabetic
      retinopathy, and axial length. It was observed that incomplete PVD could lead to
      sight-threatening diabetic retinopathy. CONCLUSION: We report the prevalence and
      risk factors of PVD in subjects with diabetes mellitus. Incomplete PVD is a major
      risk factor for sight-threatening diabetic retinopathy.

PMID- 22476625
TI  - Mitochondrial oxidative stress initiates visual loss in sympathetic ophthalmia.
AB  - The visual loss that occurs with sympathetic ophthalmia (SO) in the absence of
      recognizable retinal damage and inflammatory cell infiltration is an enigma.
      Experimental autoimmune uveoretinitis (EAU) is an animal model used to study
      human endogenous uveitis. Both innate and adaptive immune responses have been
      well studied in the photoreceptor damage mechanism of EAU. In our studies, in the
      early phase of EAU, proinflammatory molecules such as tumor necrosis factor (TNF)
      alpha and inducible nitric oxide synthase (iNOS) and the subsequent mitochondrial
      DNA damage, mitochondrial protein alteration, and mitochondrial dysfunction by
      oxidative stress were observed before retinal inflammatory cell infiltration. Our
      recent study shows the importance of Toll-like receptors (TLRs) in the production
      of proinflammatory molecules and the induction of mitochondrial oxidative stress.
      Thus, the innate immune responses occur first with the activation of TLRs; this
      activation upregulates proinflammatory molecules, leading to mitochondrial
      oxidative stress before retinal inflammatory cell infiltration and the subsequent
      adaptive immune responses. Like EAU, SO also results in photoreceptor
      mitochondrial oxidative damage without retinal inflammatory cell infiltration.
      Such damage was associated with TNF-alpha, TNF-alpha receptors, and iNOS
      expression in the photoreceptors, suggesting that this molecular mechanism
      without retinal inflammatory cell infiltration may initiate photoreceptor damage
      in SO.

PMID- 22476627
TI  - Correlation between visual sensitivity loss and years affected for eyes with
      retinitis pigmentosa.
AB  - PURPOSE: To determine the best clinical measures of visual sensitivity for
      monitoring disease progression in eyes with retinitis pigmentosa (RP). METHODS:
      This survey retrospectively studied results from the Humphrey perimetry central
      10-2 program for 123 eyes with RP with regard to the correlation between years
      affected by RP and clinical measures of visual dysfunction, including mean
      deviation (MD), average sensitivity of 12 test points (CENT12), average
      sensitivity of 4 central points (CEN4), foveal threshold (FT), and logarithm of
      the minimum angle of resolution (LogMAR). RESULTS: All these value correlated
      more highly with years of symptoms (P < 0.001 for all) than with years since
      diagnosis. The correlation coefficient with years of symptoms decreased in the
      order MD, CENT12, CENT4, FT, and LogMAR. The order differed for a subset of 66
      eyes with advanced RP having -15 dB or lower MD, and decreased in the order FT,
      CENT4, LogMAR and CENT12. CONCLUSION: Progression in eyes with RP could be well
      assessed by use of the MD of the Humphrey central 10-2 program in general and by
      use of FT, CENT4, and CENT12 in cases of advanced RP.

PMID- 22476629
TI  - Practical Implementation of New Particle Tracking Method to the Real Field of
      Groundwater Flow and Transport.
AB  - In articles published in 2009 and 2010, Suk and Yeh reported the development of
      an accurate and efficient particle tracking algorithm for simulating a path line
      under complicated unsteady flow conditions, using a range of elements within
      finite elements in multidimensions. Here two examples, an aquifer storage and
      recovery (ASR) example and a landfill leachate migration example, are examined to
      enhance the practical implementation of the proposed particle tracking method,
      known as Suk's method, to a real field of groundwater flow and transport. Results
      obtained by Suk's method are compared with those obtained by Pollock's method.
      Suk's method produces superior tracking accuracy, which suggests that Suk's
      method can describe more accurately various advection-dominated transport
      problems in a real field than existing popular particle tracking methods, such as
      Pollock's method. To illustrate the wide and practical applicability of Suk's
      method to random-walk particle tracking (RWPT), the original RWPT has been
      modified to incorporate Suk's method. Performance of the modified RWPT using
      Suk's method is compared with the original RWPT scheme by examining the
      concentration distributions obtained by the modified RWPT and the original RWPT
      under complicated transient flow systems.

PMID- 22476628
TI  - Endomyocardial biopsy in a patient with hemorrhagic pheochromocytoma presenting
      as inverted Takotsubo cardiomyopathy.
AB  - A 29-year-old female patient presented with shock and dyspnea due to heart
      failure and pulmonary edema. Echocardiography indicated excessive contraction
      limited to the left ventricular apex and akinesis of the basal and middle
      ventricle, which were confirmed by emergency left ventriculography. The finding
      was diagnostic of inverted Takotsubo cardiomyopathy. An abdominal computed
      tomography scan showed a tumor in the left adrenal gland with a central low
      density area, and the plasma and urinary catecholamines were strikingly elevated.
      Taken together, these findings suggested the presence of a hemorrhagic
      pheochromocytoma. A myocardial biopsy in the very acute stage on the day of
      admission revealed neutrophilic infiltration and contraction-band necrosis, which
      was indistinguishable from the previously reported pathology in the acute phase
      of idiopathic Takotsubo cardiomyopathy without pheochromocytoma. The diagnosis of
      pheochromocytoma in this case was confirmed 7 weeks later by surgical removal of
      the left adrenal gland with massive hemorrhage at the center of the
      pheochromocytoma. The marked similarity of the endomyocardial pathology between
      this case and cases with idiopathic Takotsubo cardiomyopathy strongly points to
      catecholamine excess as a common causality for Takotsubo cardiomyopathy with or
      without pheochromocytoma.

PMID- 22476630
TI  - The effects of cognitive: linguistic variables and language experience on
      behavioural and kinematic performances in nonword learning.
AB  - The aim of the present study was to investigate the effects of cognitive
      linguistic variables and language experience on behavioral and kinematic measures
      of nonword learning in young adults. Group 1 consisted of thirteen participants
      who spoke American English as the first and only language. Group 2 consisted of
      seven participants with varying levels of proficiency in a second language.
      Logistic regression of the percent of correct productions revealed short-term
      memory to be a significant contributor. The bilingual group showed better
      performance compared to the monolinguals. Linear regression of the kinematic data
      revealed that the short-term memory variable contributed significantly to
      movement coordination. Differences were not observed between the bilingual and
      the monolingual speakers in kinematic performance. Nonword properties including
      syllable length and complexity influenced both behavioral and kinematic
      performance. The findings supported the observation that nonword repetition is
      multiply determined in adults.

PMID- 22476631
TI  - The bisecting GlcNAc in cell growth control and tumor progression.
AB  - The bisecting GlcNAc is transferred to the core mannose residue of complex or
      hybrid N-glycans on glycoproteins by the beta1,4-N-acetylglucosaminyltransferase
      III (GlcNAcT-III) or MGAT3. The addition of the bisecting GlcNAc confers unique
      lectin recognition properties to N-glycans. Thus, LEC10 gain-of-function Chinese
      hamster ovary (CHO) cells selected for the acquisition of ricin resistance, carry
      N-glycans with a bisecting GlcNAc, which enhances the binding of the
      erythroagglutinin E-PHA, but reduces the binding of ricin and galectins-1, -3 and
      -8. The altered interaction with galactose-binding lectins suggests that the
      bisecting GlcNAc affects N-glycan conformation. LEC10 mutants expressing polyoma
      middle T antigen (PyMT) exhibit reduced growth factor signaling. Furthermore,
      PyMT-induced mammary tumors lacking MGAT3, progress more rapidly than tumors with
      the bisecting GlcNAc on N-glycans of cell surface glycoproteins. In recent years,
      evidence for a new paradigm of cell growth control has emerged involving
      regulation of cell surface residency of growth factor and cytokine receptors via
      interactions and cross-linking of their branched N-glycans with a lattice of
      galectin(s). Specific cross-linking of glycoprotein receptors in the lattice
      regulates their endocytosis, leading to effects on growth factor-induced
      signaling. This review will describe evidence that the bisecting GlcNAc of N
      glycans regulates cellular signaling and tumor progression, apparently through
      modulating N-glycan/galectin interactions.

PMID- 22476632
TI  - A novel "pelvic ring augmentation construct" for lumbo-pelvic reconstruction in
      tumour surgery.
AB  - AIM: Reconstructing or augmenting the lumbo-pelvic junction after resection of L5
      and part of the sacrum is challenging. Numerous lumbo-pelvic reconstruction
      methods based on posterior construct and anterior cages have been proposed for
      cases involving total sacrectomy and lumbar vertebrectomy. These constructs
      create long lever arms and generate high cantilever forces across the lumbo
      sacral junction, resulting in implant failure or breakage. Biomechanical studies
      have shown that placing implants anterior to lumbo-sacral pivot point provides a
      more effective moment arm to resist flexion force and improves the ultimate
      strength of the construct. We present here a novel method to augment a lumbo
      pelvic construction using a pelvic ring construct. METHODS: A 69-year-old lady
      presented with implant failure of her two previous posterior lumbo-pelvic
      reconstructions performed by the authors. She initially presented, two and a half
      years previously with 6 months history of back pain with normal neurological
      function. MRI scans of her whole spine showed isolated secondaries in the lumbar
      spine (L4, L5) and sacrum (S1). An abdominal CT scan revealed a primary tumour in
      her right kidney. Briefly, the first surgery involved a single-stage removal of
      posterior elements of L4 and L5 and posterior stabilisation from L2 to pelvis,
      anterior resection of L4 and L5 and partially S1 with implantation of an
      expandable Synex II cage. The cage was replaced with an anterior rod construct
      from L2 and L3 to a trans-sacral screw a week later as it had dislodged. The
      second revision, 9 months later, involved removal of two posterior broken rods
      which were replaced and converted into a modified four-rod construct. While
      monitoring her progress, it was subsequently noted that the trans-sacral rod had
      broken. Therefore, it was decided to augment her lumbo-pelvic construct to
      prevent eventual catastrophic posterior construct failure. From a posterior
      approach, contoured rods were passed bilaterally along the inner table of the
      pelvis under the iliacus muscle up to the anterior border of the pelvis. Using T
      connectors, the rods were connected to the posterior lumbo-pelvic construct.
      Thereafter, two anterior supra-acetabular pelvic screws were connected to a
      subcutaneously placed rod matched to the shape of the anterior abdominal wall.
      The pelvic ring construct was completed on connecting this rod with T-connectors
      to the free ends of the contoured iliac rods. RESULTS AND CONCLUSION: There were
      no intra-operative complications. At the end of 12 months, she was mobilising
      with a frame, with no radiological evidence of failure of the construct. However,
      she died due to disease progression at the end of 15 months. Experience from one
      clinical case shows that such a construct is feasible and adds a technical option
      to the difficult reconstruction of lumbo-pelvic junction after tumour surgery.

PMID- 22476633
TI  - Expert's comment concerning Grand Rounds case entitled "a novel 'pelvic ring
      augmentation construct' for lumbo-pelvic reconstruction in tumor surgery" (by
      Sathya Thambiraj, Daren Forward, James Thomas and Bronek Boszczyk).
AB  - INTRODUCTION: Historically, metastatic spine tumor surgery has been palliative
      for pain control, to maintain neurologic and ambulatory function. The thought of
      curing cancer with limited metastatic disease by resecting the primary and the
      metastatic lesions is becoming more common. Multilevel spondylectomy for
      resection of metastatic disease has been reported in the literature, mostly at
      the thoracic or lumbar level with some success. Reconstruction of the lumbosacral
      junction after tumor resection is a difficult endeavor and several techniques
      have been utilized. Subcutaneous anterior pelvic fixation has been described for
      the treatment of unstable pelvic fractures. MATERIALS AND METHODS: Review of the
      Grand Rounds case "A novel Pelvic Ring Augmentation Construct for Lumbo-Pelvic
      Reconstruction in Tumour Surgery" by Sathya Thambiraj, Daren Forward, James
      Thomas, Bronek Boszczyk and review of the pertinent literature. CONCLUSION: The
      authors describe a novel percutaneous rod technique and construct for buttressing
      a posterior spinal construct to a subcutaneous anterior pelvic fixator after
      tumor resection of the lumbo-pelvic junction. They manage to salvage a difficult
      situation for which they should be commended. This technique may be useful in
      situations where instrumentation has to be preformed to the pelvis: i.e., in
      tumor reconstruction, fusions such as neuromuscular scoliotic disease to the
      pelvis, to augment a lumbo-pelvic construct when a nonunion occurs or in
      osteoporotic patients as a salvage procedure.

PMID- 22476636
TI  - Effect of prosthesis endplate lordosis angles on L5-S1 kinematics after disc
      arthroplasty.
AB  - OBJECTIVE: We hypothesized that L5-S1 kinematics will not be affected by the
      lordosis distribution between the prosthesis endplates. MATERIALS AND METHODS:
      Twelve cadaveric lumbosacral spines (51.3 +/- 9.8 years) were implanted with 6
      degrees  or 11 degrees  prostheses (ProDisc-L) with four combinations of
      superior/inferior lordosis (6 degrees /0 degrees , 3 degrees /3 degrees , 11
      degrees /0 degrees , 3 degrees /8 degrees ). Specimens were tested intact and
      after prostheses implantation with different lordosis distributions. Center of
      rotation (COR) and range of motion (ROM) were quantified. RESULTS: Six-degree
      lordosis prostheses (n = 7) showed no difference in flexion-extension ROM,
      regardless of design (6 degrees /0 degrees  or 3 degrees /3 degrees ) (p > 0.05).
      In lateral bending (LB), both designs reduced ROM (p < 0.05). In axial rotation,
      only the 3 degrees /3 degrees  design reduced ROM (p < 0.05). Eleven-degree
      lordosis prostheses (n = 5) showed no difference in flexion-extension ROM for
      either design (p > 0.05). LB ROM decreased with distributed lordosis prostheses
      (3 degrees /8 degrees ) (p < 0.05). Overall, L5-S1 range of motion was not
      markedly influenced by lordosis distribution among the two prosthesis endplates.
      The ProDisc-L prosthesis design where all lordosis is concentrated in the
      superior endplate yielded COR locations that were anterior and caudal to intact
      controls. The prosthesis with lordosis distributed between the two endplates
      yielded a COR that tended to be closer to intact. CONCLUSIONS: Further clinical
      and biomechanical studies are needed to assess the long-term impact of lordosis
      angle distribution on the fate of the facet joints.

PMID- 22476638
TI  - Percutaneous augmented instrumentation of unstable thoracolumbar burst fractures:
      our experience in preventing cement leakage.

PMID- 22476641
TI  - Association of lipopolysaccharide-binding protein gene polymorphisms with
      cerebral infarction in a Chinese population.
AB  - Toll-like receptors (TLRs) have been widely known for their role as an important
      mediator of immune reactions in the development and progression of
      atherosclerotic (AS) lesions, which play the most important role in the
      occurrence of cerebral infarction (CI). The lipopolysaccharide (LPS)
      lipopolysaccharide binding protein (LBP) compounds connect LPS receptor-CD14 and
      play an important role in promoting inflammatory reaction through TLRs. This
      study was designed to study whether LBP genetic polymorphisms are associated with
      CI risk in a Chinese population. LBP c.291T>C and c.1306T>C single nucleotide
      polymorphisms (SNPs) were genotyped in 366 CI cases and 200 controls from
      Changsha by using method of Polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP). Blood lipid and lipoprotein levels were also detected
      and the intima-media thickness (IMT) of carotid arteries were determined. No
      significant difference in genotype and allele distribution of the LBP c.291T>C
      and LBP c.1306T>C polymorphism was observed between the cases and controls (P >
      0.05). CI patients carrying the TC genotype for both LBP c.291T>C and c.1306T>C
      polymorphisms showed higher carotid IMT than those carrying the TT genotype (P <
      0.05, respectively). LBP c.291T>C and c.1306T>C polymorphisms were significantly
      associated with carotid IMT in Changsha, China, but both polymorphisms were not
      associated with risk of atherosclerotic CI.

PMID- 22476642
TI  - Differentiating ischemic from non-ischemic chest pain using white blood cell
      surface inflammatory and coagulation markers.
AB  - Chest pain is one of the most common complaints seen in emergency departments
      (ED), up to 5-8 % of all ED visits. About 50-60 % of chest pain patients
      presenting to the ED are hospitalized. Seventy percentage of those patients not
      discharged from the ED are subsequently shown to not have acute cardiac disease.
      It has been estimated that emergency physician miss 2-6 % of acute coronary
      syndrome (ACS) that present to ED. While admitting a non-ACS patient is a
      financial burden on the medical system, releasing to home an undiagnosed ACS
      patient has life-threatening consequences. This study used flow cytometry to
      evaluate a panel of mononuclear cells, neutrophils, cytokines and fibrinolytic
      activation markers in patients presenting in ED with acute chest pain. The goal
      was to add diagnostic tools to the differentiation between true ischemic cardiac
      and non-ischemic chest pain in the process of triage. The study population
      consisted of 74 consecutive patients presenting with acute chest pain to the
      emergency department of Ziv Medical Center and were admitted to Intensive Cardiac
      Care Unit or Internal Wards of our hospital during the period September 2009 to
      February 2010. ACS has been clearly associated with a decrease in CD89+/CD62L+
      population, an increase in percentage of cytotoxic T-cell subset, and an increase
      in platelet marker. Differences in thrombin receptor surface expression were also
      noted. The combination of multiple biomarkers may help to enhance diagnostic
      accuracy.

PMID- 22476643
TI  - Screening of cerebral infarction-related genetic markers using a Cox regression
      analysis between onset age and heterozygosity at randomly selected short tandem
      repeat loci.
AB  - The aim of this paper is to explore whether the heterozygosity at the 9 CODIS
      short tandem repeats (STR) loci including D3S1358, vWA, FGA, D8S1179, D21S11,
      D18S51, D5S818, D13S317 and D7S820 is associated with the risk of atherosclerotic
      cerebral infarction (CI). The DNA samples were collected from patients with CI (n
      = 72) and people over the age of 90 years without CI (n = 59). Alleles of the STR
      loci were determined using the STR Profiler Plus PCR amplification kit. The
      relationship between the age of onset and heterozygosity was determined with the
      Cox regression method. A correlation between the age of onset and heterozygosity
      was observed for the D8S1179 locus (p < 0.05). It implied that regions in the
      vicinity of locus D8S1179 may harbor susceptibility genes for CI. The analysis of
      heterozygosity for particular loci as genetic markers using our new study design
      may be an efficient and reliable approach to estimate genetic predispositions.

PMID- 22476646
TI  - Flupentixol: relevance of stereoselective therapeutic drug monitoring.

PMID- 22476648
TI  - Polybrominated diphenyl ethers disrupt molting in neonatal Daphnia magna.
AB  - Polybrominated diphenyl ethers (PBDEs) are flame-retardants which can
      bioaccumulate and biomagnify and are found worldwide despite their banned usage
      in some countries. In recent years, the possibility that PBDEs may disrupt
      endocrine functions in vertebrates has been well investigated, but little
      attention has been paid to the endocrine disrupting potential in aquatic
      invertebrates. The current study aimed to investigate whether PBDEs affect
      molting in neonatal Daphnia magna. Prior to molting studies, 48 h LC50 values
      were tested for several environmentally prevalent PBDEs: PBDEs-28, -47, -99, -100
      and -209. The 48 h LC50s determined were 110.7, 7.9, 2.6, and 11.1 MUg/L for
      PBDEs-28, -47, -99, and -100, respectively, but the highest concentration of
      PBDEs-209 tested (2.5 mg/L) did not affect survival at 48 h. Sublethal
      concentrations of these were used to investigate their potential effects on
      molting, assessed by the time taken to reach 4 molts. Molting studies found that
      PBDE-28 at 12 MUg/L significantly increased the time it took to complete 4 molts.
      PBDE-47 at 20 MUg/L inhibited daphnid molting initially but such an inhibitory
      effect disappeared with the prolongation of exposure due to the death of
      sensitive individuals. No other PBDEs affected molting at the concentrations
      tested, while still maintaining relatively high survival rates. In conclusion,
      this study found that PBDEs-28 and -47 can delay molting at MUg/L concentrations,
      which raises concern for disrupted molting in crustaceans exposed to PBDEs.

PMID- 22476649
TI  - An evaluation of the safety and feasibility of convection-enhanced delivery of
      carboplatin into the white matter as a potential treatment for high-grade glioma.
AB  - Glioblastoma multiforme (GBM) is the most common and most aggressive form of
      intrinsic brain tumour. Despite standard treatment involving surgical resection,
      chemotherapy and radiotherapy this disease remains incurable with the majority of
      tumours recurring adjacent to the resection cavity. Consequently there is a clear
      need to improve local tumour control. Convection-enhanced delivery (CED) is a
      practical technique for administering chemotherapeutics directly into
      peritumoural brain. In this study, we have tested the hypothesis that carboplatin
      would be an appropriate chemotherapeutic agent to administer by CED into
      peritumoural brain to treat GBM. Within this study we have evaluated the
      relationships between carboplatin concentration, duration of exposure and tumour
      cell kill in vitro using GBM cell lines and the relationship between carboplatin
      concentration and clinical and histological evidence of toxicity in vivo. In
      addition, we have used laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS) to evaluate the distribution properties of carboplatin
      following CED into rat brain and to determine the rate at which carboplatin is
      cleared from the brain. Finally, we have compared the distribution properties of
      carboplatin and the MRI contrast agent gadolinium-DTPA in pig brain. The results
      of these experiments confirm that carboplatin can be widely distributed by CED
      and that it remains in the brain for at least 24 h after infusion completion.
      Furthermore, carboplatin provokes a significant GBM cell kill at concentrations
      that are not toxic to normal brain. Finally, we provide evidence that gadolinium
      DTPA coinfusion is a viable technique for visualising carboplatin distribution
      using T1-weighted MR imaging.

PMID- 22476651
TI  - Novel fatty acid gentamicin salts as slow-release drug carrier systems for anti
      infective protection of vascular biomaterials.
AB  - Infections of vascular prostheses are still a major risk in surgery. The current
      work presents an in vitro evaluation of novel slow release antibiotic coatings
      based on new gentamicin fatty acid salts for polytetrafluoroethylene grafts.
      These grafts were coated with gentamicin sodium dodecyl sulfate, gentamicin
      laurate and gentamicin palmitate. Drug release kinetics, anti-infective
      characteristics, biocompatibility and haemocompatibility of developed coatings
      were compared to commercially available gelatin sealed PTFE grafts (SEALPTFETM)
      and knitted silver coated Dacron((r)) grafts (InterGard((r))). Each gentamicin
      fatty acid coating showed a continuous drug release in the first eight hours
      followed by a low continuous release. Grafts coated with gentamicin fatty acids
      reduced bacterial growth even beyond pathologically relevant high concentrations.
      Cytotoxicity levels depending on drug formulation bringing up gentamicin
      palmitate as the most promising biocompatible coating. Thrombelastography
      studies, ELISA assays and an amidolytic substrate assay confirmed
      haemocompatibility of developed gentamicin fatty acid coatings comparable to
      commercially available grafts.

PMID- 22476650
TI  - Fabrication and evaluation of electrospun collagen/poly(N-isopropyl
      acrylamide)/chitosan mat as blood-contacting biomaterials for drug delivery.
AB  - The recent advances in electrospinning have resulted in technologies facilitating
      easy drug entrapment, obtaining high surface area and thereby higher drug loading
      and release efficacy, burst control as well as the specific morphology which
      could be controlled according to the desired requirement. The present study
      focused on the fabrication of collagen/poly(N-isopropyl acrylamide)/chitosan
      complex with incorporated 5-fluorouracil, an anticancer drug by the method of
      electrospinning. The effect of chitosan on the fiber morphology and release
      kinetics was analyzed by varying its concentration. The release kinetics showed
      that the increase in chitosan concentration delayed the release of the drug from
      the fiber network. Nano hydroxyapatite was added to the fiber matrix in order to
      impart bioactivity, which was confirmed by studies in simulated body fluid. The
      addition of poly(N-isopropyl acrylamide) increased the blood compatibility of the
      prepared model. Thus, the model prepared to can find potential application in the
      field of cancer therapy as a drug-delivery agent in post-surgical treatment of
      cancer and as blood contacting biomaterial.

PMID- 22476652
TI  - Case of Mycobacterium tuberculosis meningitis: Gram staining as a useful initial
      diagnostic clue for tuberculous meningitis.
AB  - A 32-year-old man was admitted to our hospital because of fever, headache, and
      loss of consciousness. Four days before admission, he had had difficulty
      speaking. On the day of admission, his colleague had found him to be unconscious
      and lying on his back. He was admitted to our hospital. The temperature at the
      eardrum was 35.2 degrees C. Neurologic evaluation was negative. Computed
      tomography (CT) scan of the brain showed slight ventricular enlargement
      bilaterally. An X-ray film of the chest showed no abnormality. On the second
      hospital day, neck stiffness was noted. The cerebrospinal fluid (CSF) contained
      870 white cells/MUl, most of which were neutrophils; the glucose level in the CSF
      was 10 mg/dl, and the protein level was 140 mg/dl. Stained smears of the CSF,
      including Gram staining and India-ink preparations, disclosed no microorganisms.
      Capsular antigen tests for several bacteria were negative. Antimicrobial agents
      were started. However, by changing the microscope focus slightly while viewing
      Gram stains of the CSF, we could see brightened and Gram-positive bacilli that
      had been phagocytosed by neutrophils. This finding suggested the presence of
      Mycobacterium tuberculosis. Ziehl-Neelsen staining of the CSF and gastric juice
      revealed anti-acid bacilli. Polymerase chain reaction for M. tuberculosis in the
      gastric juice was positive. This case showed that Gram staining could be useful
      as an initial adjunct for the diagnosis of tuberculous meningitis, particularly
      when the CSF shows predominantly neutrocytic pleocytosis, but no other evidence
      of bacterial meningitis.

PMID- 22476653
TI  - Upper respiratory tract infection and torticollis in children: differential
      diagnosis of Grisel's syndrome.

PMID- 22476654
TI  - Anti-human hepatoma Hep-G2 proliferative, apoptotic, and antimutagenic activity
      of tagitinin C from Tithonia diversifolia leaves.
AB  - Tagitinin C, a major sesquiterpenoid, was isolated from the leaves of Tithonia
      diversifolia. The high morbidity and mortality rate of hepatoma in Taiwan
      motivated our interest in the investigation of tagitinin C's mechanism against
      the human hepatocellular carcinoma. The methanolic extract of leaves of T.
      diversifolia (TDM) and tagitinin C were found to have cytotoxic activities
      against human hepatoma Hep-G2 cells in the MTT assay with IC(50) values of 40.0
      +/- 2.0 and 2.0 +/- 0.1 MUg/mL, respectively. This compound induced population
      increase in the sub-G(1) phase and S phase arrest. Treatment with tagitinin C
      isolated from TDM resulted in activation of both caspase 3 and caspase 8 which
      suggested that the antiproliferative effect of this compound was caspase
      dependent apoptosis. Magnetic resonance techniques indicated that the
      tumorigenisity of xenografts derived from Hep-G2 cells was retarded by the
      delivery of tagitinin C (15 MUg/mouse/day) relative to the control counterparts.

PMID- 22476655
TI  - Long-term efficacy of miglustat in paediatric patients with Niemann-Pick disease
      type C.
AB  - Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease
      characterized by progressive neurological manifestations. Oral miglustat was
      first approved for the treatment of children and adults with NP-C in Europe in
      2009. There are still relatively few published data on the long-term efficacy and
      safety of miglustat in patients with NP-C in clinical practice. We report the
      effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five
      children. Overall, 3/5 patients displayed progressive dysphagia before starting
      miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age
      at treatment start was 11.6 years, and the median (range) duration of therapy so
      far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but
      therapy was interrupted for 1-3 months at least once in all patients due to
      supply issues. Swallowing function was stabilised during miglustat therapy, with
      no significant increase in Han dysphagia scale or aspiration-penetration index
      scores among four evaluable patients (p > 0.05). Scores on the mini-mental state
      examination indicated an improvement in cognitive function during the first 3-6
      months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory
      function remained stable for at least the first 2 years of treatment in most
      patients, but there was a trend towards deterioration thereafter, possibly
      related to treatment interruptions. The safety/tolerability profile of miglustat
      was similar to previous clinical studies, although reports of gastrointestinal
      disturbances were rare. Overall, miglustat appeared to stabilise key parameters
      of neurological disease progression.

PMID- 22476656
TI  - Pathogenesis and molecular targeted therapy of spinal and bulbar muscular atrophy
      (SBMA).
AB  - Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is an
      adult-onset, X-linked motor neuron disease characterized by muscle atrophy,
      weakness, contraction fasciculations, and bulbar involvement. SBMA is caused by
      the expansion of a CAG triplet repeat, encoding a polyglutamine tract within the
      first exon of the androgen receptor (AR) gene. The histopathological finding in
      SBMA is the loss of lower motor neurons in the anterior horn of the spinal cord
      as well as in the brainstem motor nuclei. There is no established disease
      modifying therapy for SBMA. Animal studies have revealed that the pathogenesis of
      SBMA depends on the level of serum testosterone, and that androgen deprivation
      mitigates neurodegeneration through inhibition of nuclear accumulation and/or
      stabilization of the pathogenic AR. Heat shock proteins, the ubiquitin-proteasome
      system and transcriptional regulation are also potential targets for development
      of therapy for SBMA. Among these therapeutic approaches, the luteinizing hormone
      releasing hormone analogue, leuprorelin, prevents nuclear translocation of
      aberrant AR proteins, resulting in a significant improvement of disease phenotype
      in a mouse model of SBMA. In a phase 2 clinical trial of leuprorelin, the
      patients treated with this drug exhibited decreased mutant AR accumulation in
      scrotal skin biopsy. Phase 3 clinical trial showed the possibility that
      leuprorelin treatment is associated with improved swallowing function
      particularly in patients with a disease duration less than 10 years. These
      observations suggest that pharmacological inhibition of the toxic accumulation of
      mutant AR is a potential therapy for SBMA.

PMID- 22476657
TI  - Extrinsic cellular and molecular mediators of peripheral axonal regeneration.
AB  - The ability of injured peripheral nerves to regenerate and reinnervate their
      original targets is a characteristic feature of the peripheral nervous system
      (PNS). On the other hand, neurons of the central nervous system (CNS), including
      retinal ganglion cell (RGC) axons, are incapable of spontaneous regeneration. In
      the adult PNS, axonal regeneration after injury depends on well-orchestrated
      cellular and molecular processes that comprise a highly reproducible series of
      degenerative reactions distal to the site of injury. During this fine-tuned
      process, named Wallerian degeneration, a remodeling of the distal nerve fragment
      prepares a permissive microenvironment that permits successful axonal regrowth
      originating from the proximal nerve fragment. Therefore, a multitude of adjusted
      intrinsic and extrinsic factors are important for surviving neurons, Schwann
      cells, macrophages and fibroblasts as well as endothelial cells in order to
      achieve successful regeneration. The aim of this review is to summarize relevant
      extrinsic cellular and molecular determinants of successful axonal regeneration
      in rodents that contribute to the regenerative microenvironment of the PNS.

PMID- 22476658
TI  - The changing spectrum of arrhythmogenic (right ventricular) cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a clinically and
      genetically heterogeneous heart muscle disorder associated with ventricular
      arrhythmias and risk of sudden death. The disease is heredo-familial, and
      mutations in desmosomal genes have been identified in about half of patients.
      Recent experimental models confirm this disease develops after birth due to
      progressive myocardial dystrophy. Genotype-phenotype correlations, including
      magnetic resonance and pathology studies on heart specimens, are currently
      demonstrating that the spectrum of the disease is wider than initially thought
      and usually referred to with the adjective "right ventricular", with the evidence
      of biventricular or even isolated left ventricular forms, so that it is
      increasingly identified simply as "arrhythmogenic cardiomyopathy". A revision of
      the diagnostic criteria encompassing familial, electrocardiographic, arrhythmic,
      morpho-functional and histopathologic findings, has been made to improve
      diagnostic sensitivity and specificity, in particular of the concealed forms and
      left-dominant subtypes of the disease. Experimental models are mandatory to gain
      an insight into the cascade of cellular and molecular events leading from gene
      defect to myocardial dystrophy in ARVC.

PMID- 22476659
TI  - A case series of 12 patients with incidental asymptomatic Dandy-Walker syndrome
      and management.
AB  - PURPOSE: Incidentally detected asymptomatic Dandy-Walker syndrome (DWS) is
      sparsely reported in literature at extremes of age (from 1 to 75 years) in
      association with different diseases. Precipitating factors causing DWS in these
      cases to manifest in late adulthood are still unidentified. We tried to
      hypothesize the aetiology and the natural course of disease based on review of
      literature MATERIAL AND METHODS: Twelve cases of asymptomatic DWS were selected
      retrospectively in this study while being treated for some unrelated disease over
      a period of 15 years. RESULTS: All the cases had vermian hypoplasia with sizeable
      fourth ventricular cyst (more than 3 cm), large posterior fossa and with no or
      borderline ventriculomegaly on CT/MRI. The age ranged from 1 to 65 years. Five
      cases presented with head injury and four cases presented with enlarged head size
      with suboccipital protuberance (noticed in children more than 5 years). Remaining
      cases presented with either occipital encephalocele or right trigeminal neuralgia
      or fixed atlantoaxial dislocation. They were asymptomatic for DWS following
      treatment of the presenting complaints on follow-up of average duration of 4.5
      years. CONCLUSION: Presentation at extremes of age signifies that slow
      degenerative changes in communicating channels between fourth ventricular cyst
      and surrounding basal cisterns may cause asymptomatic DWS to manifest, but cases
      having good communication between these structures can remain asymptomatic
      throughout their life.

PMID- 22476660
TI  - Evaluation of cerebellar mutism by arterial spin-labeling perfusion magnetic
      resonance imaging in a patient with atypical teratoid/rhabdoid tumor (AT/RT): a
      case report.

PMID- 22476661
TI  - Running-induced headaches in an aqueduct stenosis patient.

PMID- 22476662
TI  - Association between chronic morbidity and early retirement in Italy.
AB  - OBJECTIVES: To examine the association between early retirement and presence of
      chronic morbidity in an Italian working population approaching the statutory
      pension age. METHODS: The study population consisted of men and women aged 45-59
      years, employed at some time in the past (n = 18,547), who participated in a
      national cross-sectional survey, conducted in 2005. By means of a standardized
      questionnaire, information was collected on employment status, chronic diseases,
      and sociodemographics. The outcome was being retired as of the survey date. The
      association with number of diseases reported and specific long-term illnesses was
      assessed through multivariate Poisson regression models with robust standard
      errors, adjusted for potential confounders (p < 0.05). RESULTS: In the final
      multivariable models, people with poorer health were more likely to retire
      earlier. Diseases of the nervous system, malignant tumors, myocardial infarction,
      other cardiac diseases, and arthrosis/arthritis were the illnesses most strongly
      associated with early retirement; furthermore, the risk of retirement increased
      linearly as the number of diseases reported increased. Among other covariates,
      age, area of residence, educational level, and occupational social class were
      also significantly associated with the outcome. Occupational social class
      significantly modified the association between morbidity and retirement in men,
      among whom a higher risk of retirement associated with morbidity was observed in
      the highest, compared with lower social classes. CONCLUSIONS: A statistically
      significant and independent association between chronic morbidity and early
      retirement was observed among subjects approaching the statutory pension age,
      suggesting the need to develop interventions to improve prevention and treatment
      of chronic conditions.

PMID- 22476663
TI  - Chemical and mechanical signaling in epithelial spreading.
AB  - We propose a minimal mathematical model to explain long-range coordination of
      dynamics of multiple cells in epithelial spreading, which may be induced, under
      different conditions, by a chemical signal, or mechanically induced strain, or
      both. The model is based on chemo-mechanical interactions including a chemical
      effect of strain, chemically induced polarization and active traction, and
      interaction between polarized cells. The results, showing kinase concentration
      distribution and cell displacement, velocity, and stress fields, allow us to
      reproduce qualitatively available experimental data and distinguish between
      distinct dynamical patterns observed under conditions of injury or
      unconstraining.

PMID- 22476664
TI  - Multidetector CT of right-sided congenital diaphragmatic hernia associated with
      hepatopulmonary fusion in a newborn.
AB  - We present a neonate with a complex congenital cardiopathy and a right-sided
      diaphragmatic hernia complicated with hepatopulmonary fusion. Radiography,
      abdominal US and multidetector CT (MDCT) demonstrated right-sided lung hypoplasia
      and liver herniation. In addition, MDCT angiography showed abnormal pulmonary
      vascular anatomy. At surgery, a right-sided diaphragmatic hernia with a partially
      herniated liver and hepatopulmonary fusion was confirmed. There was no aberrant
      systemic vascular supply towards the lower lobe, as seen in extralobar
      sequestration. MDCT angiography of the chest and upper abdomen with optimal
      enhancement and reconstruction of the pulmonary and hepatic vasculature can
      demonstrate associated anomalies in cases of suspected primary or secondary right
      lung hypoplasia.

PMID- 22476665
TI  - Simulating land-cover change in Montane mainland southeast Asia.
AB  - We used the conversion of land use and its effects (CLUE-s) model to simulate
      scenarios of land-cover change in Montane mainland southeast Asia (MMSEA), a
      region in the midst of transformation due to rapid intensification of agriculture
      and expansion of regional trade markets. Simulated changes affected approximately
      10 % of the MMSEA landscape between 2001 and 2025 and 16 % between 2001 and 2050.
      Roughly 9 % of the current vegetation, which consists of native species of trees,
      shrubs, and grasses, is projected to be replaced by tree plantations, tea, and
      other evergreen shrubs during the 50 years period. Importantly, 4 % of this
      transition is expected to be due to the expansion of rubber (Hevea brasiliensis),
      a tree plantation crop that may have important implications for local-to-regional
      scale hydrology because of its potentially high water consumption in the dry
      season.

PMID- 22476666
TI  - An evaluation of several in-lake restoration techniques to improve the water
      quality problem (eutrophication) of Saint-Augustin Lake, Quebec, Canada.
AB  - Increasing phosphorus (P) content and decreasing water quality of Saint-Augustin
      Lake, Quebec City, Canada, has led to implementation of an Integrated Watershed
      Management Plan to restore the lake. As a part of the plan, the effects of
      different restoration techniques on lake water quality and biological community
      (i.e., biological compatibility) were assessed during an isolated water enclosure
      study and laboratory microcosm assay, respectively. The restoration techniques
      include: (i) coagulation of P by alum only (20 mg L(-1)), (ii) active capping of
      sediments using a calcite layer of 10 cm, and (iii) a complete method involving
      both alum coagulation and calcite capping. The results showed that the total P
      (TP) was greatly decreased (76-95 %) by alum + calcite, followed by calcite only
      (59-84 %). Secchi depth was 106 % greater and chlorophyll a concentrations were
      declined by 19-78 % in the enclosure which received both alum and calcite.
      Results of the biological compatibility test showed that total phytoplankton
      biomass declined by 31 % in microcosms composed of alum + calcite. No significant
      (P > 0.05) toxic effect was found on the survival of Daphnia magna and Hyalella
      azteca in both alum only and alum + calcite microcosms. Although the alum +
      calcite technique impaired the survival of Chironomus riparius, the midge
      emergence was much higher compared to alum only and control. Overall, the alum +
      calcite application was effective in controlling P release from sediment and
      lowering water column P concentrations, and thus improving the water quality and
      aquatic life of Saint-Augustin Lake. However, the TP concentrations are still
      higher than the critical limit (20 MUg L(-1)) for aquatic life and the water
      column remained in the eutrophic state even after treatment. Increased TP
      concentrations, to higher than ambient levels of the lake, in the water column of
      all four enclosures, due to bioturbation artefact triggered by the platform
      installation, likely cause insufficient dosages of alum and/or calcite applied
      and reduced their effectiveness.

PMID- 22476667
TI  - Dynamics of plains cottonwood (Populus deltoides) forests and historical
      landscape change along unchannelized segments of the Missouri River, USA.
AB  - Construction of six large dams and reservoirs on the Missouri River over the last
      50-75 years has resulted in major landscape changes and alterations in flow
      patterns, with implications for riparian forests dominated by plains cottonwood
      (Populus deltoides). We quantified changes in land cover from 1892-1950s and the
      1950s-2006 and the current extent and age structure of cottonwood forests on
      seven segments (two reservoir and five remnant floodplain) comprising 1127 km (53
      %) of the unchannelized upper two-thirds of the Missouri River. Riparian forest
      area declined by 49 %; grassland 61 %; shrubland 52 %; and sandbar habitat 96 %;
      while agricultural cropland increased six-fold and river/reservoir surface area
      doubled from 1892 to 2006. Net rates of erosion and accretion declined between
      the 1892-1950s and 1950s-2006 periods. Accretion exceeded erosion on remnant
      floodplain segments, resulting in declines in active channel width, particularly
      in 1950s-2006. Across all study segments in 2006, most cottonwood stands (67 %)
      were >50 years old, 22 % were 25-50 years old, and only 10 % were <25 years old.
      Among stands <50 years old, the higher proportion of 25-50 year old stands
      represents recruitment that accompanied initial post-dam channel narrowing; while
      declines in sandbar and shrubland area and the low proportion of stands <25 years
      old suggest declines in geomorphic dynamism and limited recruitment under recent
      river management. Future conservation and restoration efforts should focus both
      on limiting further loss of remnant cottonwood stands and developing approaches
      to restore river dynamics and cottonwood recruitment processes.

PMID- 22476668
TI  - Building co-management as a process: problem solving through partnerships in
      Aboriginal country, Australia.
AB  - Collaborative problem solving has increasingly become important in the face of
      the complexities in the management of resources, including protected areas. The
      strategy undertaken by Girringun Aboriginal Corporation in north tropical
      Queensland, Australia, for developing co-management demonstrates the potential
      for a problem solving approach involving sequential initiatives, as an
      alternative to the more familiar negotiated agreements for co-management. Our
      longitudinal case study focuses on the development of indigenous ranger units as
      a strategic mechanism for the involvement of traditional owners in managing their
      country in collaboration with government and other interested parties. This was
      followed by Australia's first traditional use of marine resources agreement, and
      development of a multi-jurisdictional, land to sea, indigenous protected area. In
      using a relationship building approach to develop regional scale co-management,
      Girringun has been strengthening its capabilities as collaborator and regional
      service provider, thus, bringing customary decision-making structures into play
      to 'care for country'. From this evolving process we have identified the key
      components of a relationship building strategy, 'the pillars of co-management'.
      This approach includes learning-by-doing, the building of respect and rapport,
      sorting out responsibilities, practical engagement, and capacity-building.

PMID- 22476669
TI  - Organic matter loading affects lodgepole pine seedling growth.
AB  - Organic matter plays important roles in returning nutrients to the soil,
      maintaining forest productivity and creating habitats in forest ecosystems.
      Forest biomass is in increasing demand for energy production, and organic matter
      has been considered as a potential supply. Thus, an important management question
      is how much organic matter should be retained after forest harvesting to maintain
      forest productivity. To address this question, an experimental trial was
      established in 1996 to evaluate the responses of lodgepole pine seedling growth
      to organic matter loading treatments. Four organic matter loading treatments were
      randomly assigned to each of four homogeneous pine sites: removal of all organic
      matter on the forest floor, organic matter loading quantity similar to whole-tree
      harvesting residuals left on site, organic matter loading quantity similar to
      stem-only-harvesting residuals, and organic matter loading quantity more similar
      to what would be found in disease- or insect-killed stands. Our 10-year data
      showed that height and diameter had 29 and 35 % increase, respectively, comparing
      the treatment with the most organic matter loading to the treatment with the
      least organic matter loading. The positive response of seedling growth to organic
      matter loading may be associated with nutrients and/or microclimate change caused
      by organic matter, and requires further study. The dynamic response of seedling
      growth to organic matter loading treatments highlights the importance of long
      term studies. Implications of those results on organic matter management are
      discussed in the context of forest productivity sustainability.

PMID- 22476670
TI  - The control of an invasive bivalve, Corbicula fluminea, using gas impermeable
      benthic barriers in a large natural lake.
AB  - Anoxia can restrict species establishment in aquatic systems and the artificial
      promotion of these conditions can provide an effective control strategy for
      invasive molluscs. Low abundances (2-20 m(-2)) of the nonnative bivalve, Asian
      clam (Corbicula fluminea), were first recorded in Lake Tahoe, CA-NV in 2002 and
      by 2010 nuisance-level population densities (>10,000 m(-2)) were observed. A non
      chemical control method using gas impermeable benthic barriers to reduce
      dissolved oxygen (DO) concentrations available to C. fluminea was tested in this
      ultra-oligotrophic natural lake. In 2009, the impact of ethylene propylene diene
      monomer (EPDM) sheets (9 m(2), n = 6) on C. fluminea beds was tested on 1-7 day
      intervals over a 56 day period (August-September). At an average water
      temperature of 18  degrees C, DO concentrations under these small barriers were
      reduced to zero after 72 h resulting in 100 % C. fluminea mortality after 28
      days. In 2010, a large EPDM barrier (1,950 m(2)) was applied to C. fluminea
      populations for 120 days (July-November). C. fluminea abundances were reduced
      over 98 % after barrier removal, and remained significantly reduced (>90 %) 1
      year later. Non-target benthic macroinvertebrate abundances were also reduced,
      with variable taxon-specific recolonization rates. High C. fluminea abundance
      under anoxic conditions increased the release of ammonium and soluble reactive
      phosphorus from the sediment substrate; but levels of unionized ammonia were low
      at 0.004-0.005 mg L(-1). Prolonged exposure to anoxia using benthic barriers can
      provide an effective short term control strategy for C. fluminea.

PMID- 22476671
TI  - Community reforms to reduce severity, chronicity, and disability of psychosis: do
      they work?

PMID- 22476672
TI  - Imaging adolescent depression treatment.

PMID- 22476673
TI  - Sex, stress, and drug cues in addiction.

PMID- 22476674
TI  - Clues to the cognitive and perceptual origins of social isolation and psychosis
      in schizophrenia.

PMID- 22476675
TI  - Remembering the "right to treatment".

PMID- 22476676
TI  - Diagnosis and treatment of postpartum obsessions and compulsions that involve
      infant harm.
AB  - Obsessive-compulsive symptoms in the postpartum period often include intrusive
      thoughts of harming the infant and rituals that result in avoidance of the baby.
      The differential diagnosis of women who develop these symptoms includes
      postpartum major mood disorders, obsessive-compulsive disorder, and psychosis
      with infanticidal thoughts. The treatment of the most common diagnoses, mood
      disorders and obsessive-compulsive disorder, includes serotonergic drugs,
      psychoeducation to help the patient understand that she is highly unlikely to
      harm her infant, and exposure with response prevention therapy. This intervention
      involves exposure of the patient to the feared situations, which are usually
      related to infant care, while simultaneously preventing the compulsive rituals.

PMID- 22476677
TI  - The flight from primary care in psychiatry.

PMID- 22476679
TI  - Religion/Spirituality and depression.

PMID- 22476680
TI  - Extended psychotherapies.

PMID- 22476688
TI  - Expansion of an exotic species and concomitant disease outbreaks: pigeon
      paramyxovirus in free-ranging Eurasian collared doves.
AB  - Eurasian collared doves (Streptopelia decaocto) have expanded their range across
      the United States since their introduction several decades ago. Recent mortality
      events in Eurasian collared doves in Arizona and Montana, USA, during the winter
      of 2009-2010 were the result of pigeon paramyxovirus (PPMV), a novel disease
      agent. The first instance of mortality by this emerging infectious disease in
      this species occurred in Florida in 2001 with subsequent disease events in 2006
      and 2008. Full diagnostic necropsies were performed on carcasses from the three
      states. PPMV was identified by RT-PCR and virus isolation and was sequenced to
      the VIb genotype of avian paramyxovirus-1 (APMV). Other APMVs are common in a
      variety of free-ranging birds, but concern is warranted because of the potential
      for commingling of this species with native birds, virus evolution, and threats
      to domestic poultry. Improved surveillance for wildlife mortality events and
      efforts to prevent introduction of non-native animals could reduce the threat of
      introducing new pathogens.

PMID- 22476689
TI  - Anthropogenic ecological change and impacts on mosquito breeding and control
      strategies in salt-marshes, Northern Territory, Australia.
AB  - Darwin, in the tropical north of Australia, is subject to high numbers of
      mosquitoes and several mosquito-borne diseases. Many of Darwin's residential
      areas were built in close proximity to tidally influenced swamps, where long-term
      storm-water run-off from nearby residences into these swamps has led to
      anthropogenic induced ecological change. When natural wet-dry cycles were
      disrupted, bare mud-flats and mangroves were transformed into perennial fresh to
      brackish-water reed swamps. Reed swamps provided year-round breeding habitat for
      many mosquito species, such that mosquito abundance was less predictable and
      seasonally dependent, but constant and often occurring in plague proportions.
      Drainage channels were constructed throughout the wetlands to reduce pooled water
      during dry-season months. This study assesses the impact of drainage
      interventions on vegetation and mosquito ecology in three salt-marshes in the
      Darwin area. Findings revealed a universal decline in dry-season mosquito
      abundance in each wetland system. However, some mosquito species increased in
      abundance during wet-season months. Due to the high expense and potentially
      detrimental environmental impacts of ecosystem and non-target species
      disturbance, large-scale modifications such as these are sparingly undertaken.
      However, our results indicate that some large scale environmental modification
      can assist the process of wetland restoration, as appears to be the case for
      these salt marsh systems. Drainage in all three systems has been restored to
      closer to their original salt-marsh ecosystems, while reducing mosquito
      abundances, thereby potentially lowering the risk of vector-borne disease
      transmission and mosquito pest biting problems.

PMID- 22476690
TI  - Understanding the relationship between religiousness, spirituality, and underage
      drinking: the role of positive alcohol expectancies.
AB  - Research has consistently found that religiousness and spirituality are
      negatively associated with underage drinking. However, there is a paucity of
      research exploring the mechanisms by which these variables influence this
      important outcome. With 344 underage young adults (ages 18-20; 61 % women), we
      investigated positive alcohol expectancies as a mediator between religiousness
      and spirituality (measured separately) and underage alcohol use. Participants
      completed the Religious Commitment Inventory-10, Daily Spiritual Experiences
      Scale, Alcohol Expectancies Questionnaire, and Drinking Styles Questionnaire.
      Results indicate less positive alcohol expectancies partially mediate the
      relationship between both religiousness and spirituality and underage alcohol
      use. This suggests religiousness and spirituality's protective influence on
      underage drinking is partly due to their influence on expectations about
      alcohol's positive effects. Since underage drinking predicts problem drinking
      later in life and places one at risk for serious physical and mental health
      problems, it is important to identify specific points of intervention, including
      expectations about alcohol that rise from religious and spiritual factors. 

PMID- 22476691
TI  - Exogenous arachidonate restores the dimethoate-induced inhibition of
      steroidogenesis in rat interstitial cells.
AB  - The present work studies the potential restorative effect of polyunsaturated
      fatty acids (PUFA, 5 MUM/24 h) on the dimethoate (DMT)-induced inhibition of
      testosterone biosynthesis in Leydig cells isolated from rat testes. Various fatty
      acids (FA) from the n-6 (18:2, 20:3, 20:4, 22:4 and 22:5) and n-3 (18.3, 20:5,
      22:5, 22:6) series were assayed in Leydig cells, alone (as delipidated BSA
      complexes) and in combination with DMT (1 ppm). The n-6 FA stimulated lipid
      peroxidation (LPO) and inhibited the activities of steroidogenic enzymes (3beta-
      and 17beta-hydroxysteroid dehydrogenases). The n-3 FA exerted an anti-oxidant
      effect, decreasing the production of thiobarbituric-acid reactive substances
      (TBARS) and inhibiting phospholipase A(2) activity. The biosynthesis of
      testosterone in DMT-treated cultures was completely normalized by ARA (20:4n-6)
      and partially restored by the addition of 20:3n-6, increasing ARA content inside
      the mitochondria. The other FA assayed failed to restore androgenesis. COX-2
      protein and prostaglandin F2alpha and E2 production were stimulated by 20:3n-6,
      ARA, 18:3n-3 and 20:5 n-3. COX-2 protein decreased upon addition of 22:5n-3 and
      22:6n-3. StAR protein was increased by ARA and partially increased by 20:3n-6,
      likely due to its metabolic conversion into ARA. Both FA increased the
      mitochondrial cholesterol pool available for testosterone biosynthesis. The rate
      of androgenesis is likely the result of various regulatory factors acting
      concomitantly on the physiology of Leydig cells.

PMID- 22476693
TI  - Accuracy of cone-beam computed tomography to assess the configuration and extent
      of ligature-induced peri-implantitis defects. A pilot study.
AB  - PURPOSE: This is a pilot study which aims to evaluate the accuracy of cone-beam
      computed tomography (CBCT) to assess the configuration and extent of ligature
      induced peri-implantitis defects. MATERIALS AND METHODS: Radiographic evaluation
      of advanced ligature-induced peri-implantitis defects (n = 9) in canine was
      performed using CBCT (central cross-sections) and compared with the corresponding
      histomorphometrical measurements of the respective site serving as a validation
      method. Deviations were calculated for the supracrestal (SC), and intrabony (IC)
      defect components, as well as defect width (DW) assessed at both vestibular (v)
      and oral (o) aspects. RESULTS: Mean differences between CBCT and histological
      analyses were -0.53 +/- 1.48 mm (SC), +0.49 +/- 1.18 mm (IC), and +0.18 +/- 0.54
      mm (DW) at vestibular aspects, and -0.13 +/- 0.44 mm (SC), -0.05 +/- 0.62 mm
      (IC), and +0.15 +/- 0.48 mm (DW) at the oral aspects (P > 0.05; paired t test,
      respectively). CONCLUSION: CBCT may represent an accurate diagnostic tool to
      estimate the histological extent of advanced peri-implantitis defects.

PMID- 22476694
TI  - Can science justify regulatory decisions about the cultivation of transgenic
      crops?
AB  - Results of scientific studies are sometimes claimed to provide scientific
      justification for regulatory decisions about the cultivation of certain
      transgenic crops. A decision may be scientifically justified if objective
      analysis shows that the decision is more likely than alternatives to lead to the
      achievement of specific policy objectives. If policy objectives are not defined
      operationally, as is often the case, scientific justification for decisions is
      not possible. The search for scientific justification for decisions leads to
      concentration on reducing scientific uncertainty about the behaviour of
      transgenic crops instead of reducing uncertainty about the objectives of policies
      that regulate their use. Focusing on reducing scientific uncertainty at the
      expense of clarifying policy objectives may have detrimental effects on
      scientists, science and society.

PMID- 22476695
TI  - Hybrid treatment of a thoracoabdominal aortic aneurysm in China: report of the
      first successful case.
AB  - Few cases of hybrid repair of thoracoabdominal aneurysm (TAAA) have been reported
      in Asian countries. The purpose of this article was to report the first
      successful hybrid repair of TAAA in China. We performed a two-stage hybrid
      surgical and endovascular procedure to manage a Safi type V TAAA with the celiac
      artery, superior mesenteric artery and bilateral renal arteries in a 45-year-old
      male with poor cardiopulmonary reserves. The patient had no complications and is
      asymptomatic 3 years after the surgery. Despite the fact that the hybrid
      procedure is based on meticulous techniques, the procedure has seldom been
      performed in China. In addition to our case report, we also summarize the
      recently published reports about hybrid repair for TAAA. The hybrid procedure
      showed a promising midterm outcome for high-risk patients with TAAA, but the late
      efficacy of this procedure should be evaluated in additional studies.

PMID- 22476696
TI  - Recovery potential of periphytic biofilms translocated in artificial streams
      after industrial contamination (Cd and Zn).
AB  - Metal wastes can significantly disturb aquatic communities, particularly
      photosynthetic organisms, the main primary producers in freshwater running
      ecosystems. In this study, biofilms and diatoms were used as bioindicators to
      characterize the kinetics of biofilm recovery. An experimental decontamination
      study was conducted under laboratory conditions, after biofilm colonisation at a
      site subject to discharge of industrial metals (Zn and Cd) and in parallel at an
      upstream site, metal-free, considered as a control. After 24 days of
      colonisation, biofilms were translocated and maintained in the laboratory for 56
      days under clean conditions (control and decontamination) or metal contamination.
      Various tests were conducted from the community level--measures of metal
      bioaccumulation, cell densities and taxonomic investigations, to the individual
      level--measures of teratological forms. After 56 days of decontamination, Zn and
      Cd concentrations in decontaminated biofilms showed a sharp decline, respectively
      ranging from 6.7 +/- 2 to 4 +/- 2.5 mg Zn g-1 DW and from 207.6 +/- 24.5 to 45.4
      +/- 9.9 MUg Cd g-1 DW. However, at the end of the experiment bioaccumulations
      remained significantly higher than concentrations in control biofilms. Despite a
      diatom evolution in biofilm assemblages, taxonomic inventories did not
      demonstrate a complete restoration of diatom communities in biofilms under
      decontamination conditions compared with controls, since metal-resistant species
      initially present after colonisation at the contaminated site, such as Eolimna
      minima, persisted in high abundance in decontaminated biofilms. Biofilms kept
      under metal pressure showed very high bioaccumulation capacities and a sharp
      decline of species diversity which allowed identification of some resistant
      species. Regarding these first results on the behaviour of diatom biofilms under
      experimental decontamination conditions, improvement of the natural hydrosystem's
      chemical state appears quickly, but an eventual return to good ecological status
      appears delayed, with the persistence of metal-tolerant species even after 56
      days.

PMID- 22476697
TI  - A metabolomics based test of independent action and concentration addition using
      the earthworm Lumbricus rubellus.
AB  - A major challenge in ecotoxicology is to understand the effects of multiple
      toxicants on organisms. Here we assess the effects on survival, weight change,
      cocoon production and metabolism caused by exposure to two similarly acting
      (imidacloprid/thiacloprid) and two dissimilarly acting (chlorpyrifos/Nickel)
      chemicals on the earthworm Lumbricus rubellus. We assessed the standard models of
      concentration addition (CA) and independent action (IA), in conjunction with a
      metabolomics based approach to elucidate mechanisms of effect. For imidacloprid
      and thiacloprid the reproductive effects indicated probable additivity. Although
      this suggests joint effects through a similar mechanism, metabolite changes for
      each pesticide actually indicated distinct effects. Further, earthworms exposed
      to a 0.5 toxic unit equitoxic mixture demonstrated metabolic effects intermediate
      between those for each pesticide, indicating a non-interactive, independent joint
      effect. For higher effect level mixtures (1 and 1.5 toxic units), metabolite
      changes associated with thiacloprid exposure began to dominate. The metabolomic
      effects of the two dissimilarly acting chemicals were distinct, confirming
      separate modes of action and both proved more toxic than anticipated from
      previous studies. In the mixtures, phenotypic effects were in accordance with IA
      estimates, while metabolite changes were dominated by Ni effects, even though
      chlorpyrifos contributed most to reproductive toxicity. This could be attributed
      to the greater systematic effect of Ni when compared to the more specifically
      acting chlorpyrifos.

PMID- 22476698
TI  - Differential transcription of heat shock protein 90 (HSP90) in the dinoflagellate
      Prorocentrum minimum by copper and endocrine-disrupting chemicals.
AB  - The dinoflagellate algae survive variations in water temperature as well as
      sudden exposures to toxic substances; heat shock proteins (HSPs) seem to function
      as part of their cell survival strategy. In the present study, we determined the
      complete open reading frame (ORF) of HSP90 gene in the dinoflagellate
      Prorocentrum minimum (PmHSP90), and examined the expression levels of the gene
      after exposure to thermal stressors, copper metal, and endocrine-disrupting
      chemicals, including bisphenol A (BPA) and polychlorinated biphenyl (PCB). The
      complete ORF of PmHSP90 was 2,130-bp long, encoding a 709-amino acid-long
      polypeptide (81.62 kDa), and bearing characteristics of the HSP90 family and
      conserved domains. Real-time (RT)-PCR analyses revealed different expression
      patterns after exposure to heat, metals, and chemicals. The expression of PmHSP90
      was significantly upregulated by increased thermal stresses, with the highest
      changes of 2.4-fold and 1.9-fold occurring after 24 h at 25  degrees C and 30 
      degrees C, respectively. The gene expression dramatically increased (2.1 to 8.9
      fold changes) with increasing concentrations of copper (one-way ANOVA, P < 0.01).
      Treatment with BPA or PCB, however, did not induce significant changes in PmHSP90
      expression. These data suggest that the dinoflagellate HSP90 responds to thermal
      stressors, but may differentially respond to toxic substances such as metals and
      endocrine-disrupting chemicals.

PMID- 22476699
TI  - Effects of selenium on calcium signaling and apoptosis in rat dorsal root
      ganglion neurons induced by oxidative stress.
AB  - Ca(2+) is well known for its role as crucial second messenger in modulating many
      cellular physiological functions, Ca(2+) overload is detrimental to cellular
      function and may present as an important cause of cellular oxidative stress
      generation and apoptosis. The aim of this study is to investigate the effects of
      selenium on lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase
      (GSH-Px), cytosolic Ca(2+) release, cell viability (MTT) and apoptosis values in
      dorsal root ganglion (DRG) sensory neurons of rats. DRG cells were divided into
      four groups namely control, H(2)O(2) (as a model substance used as a paradigm for
      oxidative stress), selenium, selenium + H(2)O(2). Moderate doses and times of
      H(2)O(2) and selenium were determined by MTT test. Cells were preterated 200 nM
      selenium for 30 h before incubatation with 1 MUM H(2)O(2) for 2 h. Lipid
      peroxidation levels were lower in the control, selenium, selenium + H(2)O(2)
      groups than in the H(2)O(2) group. GSH-Px activities were higher in the selenium
      groups than in the H(2)O(2) group. GSH levels were higher in the control,
      selenium, selenium + H(2)O(2) groups than in the H(2)O(2) group. Cytosolic Ca(2+)
      release was higher in the H(2)O(2) group than in the control, selenium, selenium
      + H(2)O(2) groups. Cytosolic Ca(2+) release was lower in the selenium + H(2)O(2)
      group than in the H(2)O(2). In conclusion, the present study demonstrates that
      selenium induced protective effects on oxidative stress, [Ca(2+)](c) release and
      apoptosis in DRG cells. Since selenium deficiency is a common feature of
      oxidative stress-induced neurological diseases of sensory neurons, our findings
      are relevant to the etiology of pathology in oxidative stress-induced
      neurological diseases of the DRG neurons.

PMID- 22476700
TI  - Multifunctional roles of NAD+ and NADH in astrocytes.
AB  - The control and maintenance of the intracellular redox state is an essential task
      for cells and organisms. NAD(+) and NADH constitute a redox pair crucially
      involved in cellular metabolism as a cofactor for many dehydrogenases. In
      addition, NAD(+) is used as a substrate independent of its redox-carrier function
      by enzymes like poly(ADP)ribose polymerases, sirtuins and glycohydrolases like
      CD38. The activity of these enzymes affects the intracellular pool of NAD(+) and
      depends in turn on the availability of NAD(+). In addition, both NAD(+) and NADH
      as well as the NAD(+)/NADH redox ratio can modulate gene expression and Ca(2+)
      signals. Therefore, the NAD(+)/NADH redox state constitutes an important
      metabolic node involved in the control of many cellular events ranging from the
      regulation of metabolic fluxes to cell fate decisions and the control of cell
      death. This review summarizes the different functions of NAD(+) and NADH with a
      focus on astrocytes, a pivotal glial cell type contributing to brain metabolism
      and signaling.

PMID- 22476703
TI  - [Chronic obstructive lung disease. A growing problem in intensive care medicine].

PMID- 22476701
TI  - Neurotransmitters and integration in neuronal-astroglial networks.
AB  - Two major neural cell types, glia, astrocytes in particular, and neurones can
      release chemical transmitters that act as soluble signalling compounds for
      intercellular communication. Exocytosis, a process which depends on an increase
      in cytosolic Ca(2+) levels, represents a common denominator for release of
      neurotransmitters, stored in secretory vesicles, from these neural cells. While
      neurones rely predominately on the immediate entry of Ca(2+) from the
      extracellular space to the cytosol in this process, astrocytes support their
      cytosolic Ca(2+) increases by appropriating this ion from the intracellular
      endoplasmic reticulum store and extracellular space. Additionally, astrocytes can
      release neurotransmitters using a variety of non-vesicular pathways which are
      mediated by an assortment of plasmalemmal channels and transporters. Once a
      neuronal and/or astrocytic neurotransmitter is released into the extracellular
      space, it can activate plasma membrane neurotransmitter receptors on neural
      cells, causing autocrine and/or paracrine signalling. Moreover, chemical
      transmission is essential not only for homocellular, but also for heterocellular
      bi-directional communication in the brain. Further detailed understanding of
      chemical transmission will aid our comprehension of the brain (dys)function in
      heath and disease.

PMID- 22476702
TI  - Maturation and aging of the human cochlea: a view through the DPOAE looking
      glass.
AB  - Cochlear function changes throughout the human lifespan. Distortion product
      otoacoustic emissions (DPOAEs) were recorded in 156 ears to examine these changes
      and speculate as to their mechanistic underpinnings. DPOAEs were analyzed within
      the context of current OAE generation theory, which recognizes distinct emission
      mechanisms. Seven age groups including premature newborns through senescent
      adults were tested with a swept-tone DPOAE protocol to examine magnitude and
      phase features of both the mixed DPOAE and individual distortion and reflection
      components. Results indicate (1) 6-8-month-old infants have the most robust DPOAE
      and component levels for frequencies >1.5 kHz; (2) older adults show a
      substantial reduction in DPOAE and distortion-component levels combined with a
      smaller drop in reflection-component levels; (3) all age groups manifest a
      violation of distortion phase invariance at frequencies below 1.5 kHz consistent
      with a secular break in cochlear scaling; the apical phase delay is markedly
      longer in newborns; and (4) phase slope of reflection emissions is most shallow
      in the older adults. Combined findings suggest that basilar membrane motion in
      the apical half of the cochlea is immature at birth and that the cochlea of
      senescent adults shows reduced nonlinearity and relatively shallow reflection
      component phase slope, which can be interpreted to suggest degraded tuning.

PMID- 22476704
TI  - [Diagnosis and therapy of COPD exacerbation].
AB  - The acute exacerbation of COPD (AECOPD) is a life-threatening clinical situation.
      This review summarizes the definition of AECOPD, the severity assessment, typical
      clinical signs and symptoms, and refers to clinical pitfalls of diagnosis and
      therapy. Important aspects of clinical history and physical examination in severe
      exacerbations are reported. The necessary accompanying examinations like chest X
      ray, blood gas analysis, ECG and echocardiography and their differential
      diagnosis as well as therapeutic significance are described. The most important
      lab examinations are summarized and controversial parameters, e.g.,
      procalcitonin, are commented upon. The differentiated need for a microbiological
      sputum screening is emphasized. The authors place special weight on the essential
      components of the therapeutic management of severe AECOPD. Practical aspects of
      uncontrolled oxygen therapy, drug selection, and application form of inhalative
      acute therapy, dose, and duration of glucocorticoids, the indication for
      antibiotics, mechanical ventilation, and also opiates are summarized.

PMID- 22476705
TI  - [Visualization of radiation effects on the central nervous system].
AB  - Therapy-related side effects, which are detectable with magnetic resonance
      imaging (MRI) at high sensitivity, are one of the most frequent causes of
      morbidity in cancer patients. They can be observed in the treatment of central
      nervous system (CNS) diseases as well as in systemic therapy, including whole
      brain irradiation and chemotherapy and are more often seen due to the better
      overall survival. This review describes the most frequent acute and chronic
      therapy-related changes in the CNS and the imaging findings. Acute changes are
      often reversible while chronic changes can be observed up to several years after
      treatment.The differentiation of treatment-related from tumor-related changes
      might be very difficult, although modern imaging modalities such as MR
      spectroscopy or MR perfusion measurements supply helpful differential diagnostic
      information.

PMID- 22476707
TI  - [Dynamic contrast-enhanced computed tomography. Tracer kinetics and radiation
      hygienic principles].
AB  - Technical innovations in multislice computed tomography (CT) allow for larger
      volume coverage in ever shorter scan times. This progress has stimulated the
      clinical application of dynamic contrast-enhanced (DCE) CT techniques, which
      offer the possibility to noninvasively characterize tissue microcirculation in
      terms of well-defined physiological quantities. This educational review imparts
      to radiologists the essential physiological terms and definitions as well as the
      basic tracer kinetic concepts required for the analysis of DCE-CT data. In
      particular, four different approaches are presented and exemplified by the
      analysis of representative DCE data: the steepest-gradient method, model-free
      algebraic deconvolution in combination with the indicator-dilution theory, two
      compartment modelling and the so-called adiabatic approximation to the
      homogeneity model. Even though DCE-CT offers substantial methodological and
      practical advantages as compared to DCE-MRI (magnetic resonance imaging), there
      are also two serious and interconnected shortcomings: the low contrast
      enhancement in relation to the noise level and the high exposure of patients to
      ionizing radiation. These limiting aspects are considered in detail from a
      radiation hygienic point of view, emphasizing the basic principles of
      justification and optimization. Clinically established as well as potential
      future applications of DCE-CT will be presented in a subsequent paper.

PMID- 22476709
TI  - Blood-plasma separation in Y-shaped bifurcating microfluidic channels: a
      dissipative particle dynamics simulation study.
AB  - The motion of a suspension of red blood cells (RBCs) flowing in a Y-shaped
      bifurcating microfluidic channel is investigated using a validated low
      dimensional RBC model based on dissipative particle dynamics. Specifically, the
      RBC is represented as a closed torus-like ring of ten colloidal particles, which
      leads to efficient simulations of blood flow in microcirculation over a wide
      range of hematocrits. Adaptive no-slip wall boundary conditions were implemented
      to model hydrodynamic flow within a specific wall structure of diverging three
      dimensional microfluidic channels, paying attention to controlling density
      fluctuations. Plasma skimming and the all-or-nothing phenomenon of RBCs in a
      bifurcating microfluidic channel have been investigated in our simulations for
      healthy and diseased blood, including the size of a cell-free layer on the
      daughter branches. The feed hematocrit level in the parent channel has
      considerable influence on blood-plasma separation. Compared to the blood-plasma
      separation efficiencies of healthy RBCs, malaria-infected stiff RBCs (iRBCs) have
      a tendency to travel into the low flow-rate daughter branch because of their
      different initial distribution in the parent channel. Our simulation results are
      consistent with previously published experimental results and theoretical
      predictions.

PMID- 22476710
TI  - First principles of copepod development help explain global marine diversity
      patterns.
AB  - A major goal of modern ecology is to understand macroecological patterns based on
      their mechanistic underpinnings. The metabolic theory of ecology predicts a
      monotonic increase of biodiversity with temperature based on the principles of
      metabolism. For marine copepods, observations have shown that while biodiversity
      does increase with temperature, the theory's prediction overestimates the slope
      of this relationship by a factor of two. By relaxing the theory's assumption that
      size is invariant with respect to temperature, and by incorporating a mechanistic
      description of copepod development into the theory, we provide an adjusted
      prediction that agrees with the observed relationship. The addition of
      development into the theory adds the potential to refine the prediction for a
      wider range of taxa, to account for discrepancies between prediction and
      observations, and to describe a wider variety of temperature-richness
      relationships.

PMID- 22476711
TI  - Distinctive life traits and distribution along environmental gradients of
      dominant and subordinate Mediterranean ant species.
AB  - For most animal and plant species, life traits strongly affect their species
      specific role, function or position within ecological communities. Previous
      studies on ant communities have mostly focused on the role of dominant species
      and the outcome of interspecific interactions. However, life traits of ant
      species have seldom been considered within a community framework. This study (1)
      analyses life traits related to ecological and behavioural characteristics of
      dominant and subordinate ant species from 13 sites distributed throughout the
      Iberian Peninsula, (2) determines how similar the ant species are within each of
      the two levels of the dominance hierarchy, and (3) establishes the distribution
      patterns of these different groups of species along environmental gradients. Our
      results showed that the differences between dominants and subordinates fall into
      two main categories: resource exploitation and thermal tolerance. Dominant
      species have more populated colonies and defend food resources more fiercely than
      subordinates, but they display low tolerance to high temperatures. We have
      identified different assemblages of species included within each of these two
      levels in the dominance hierarchy. The distribution of these assemblages varied
      along the environmental gradient, shifting from dominant Dolichoderinae and
      cryptic species in moist areas, to dominant Myrmicinae and hot climate
      specialists mainly in open and hot sites. We have been able to identify a set of
      life traits of the most common Iberian ant species that has enabled us to
      characterise groups of dominant and subordinate species. Although certain common
      features within the groups of both dominants and subordinates always emerge,
      other different features allow for differentiating subgroups within each of these
      groups. These different traits allow the different subgroups coping with
      particular conditions across environmental gradients.

PMID- 22476712
TI  - Review of laser speckle-based analysis in medical imaging.
AB  - Speckle pattern forms when a rough object is illuminated with coherent light
      (laser) and the backscattered radiation is imaged on a screen. The pattern
      changes over time due to movement in the object. Such time-integrate speckle
      pattern can be statistically analyzed to reveal the flow profile. For higher
      velocity the speckle contrast gets reduced. This theory can be utilized for
      tissue perfusion in capillaries of human skin tissue and cerebral blood flow
      mapping in rodents. Early, the technique was suffered from low resolution and
      computational intricacies for real-time monitoring purpose. However, modern
      engineering has made it feasible for real-time monitoring in microcirculation
      imaging with improved resolution. This review illustrates several modifications
      over classical technique done by many researchers. Recent advances in speckle
      contrast methods gain major interest, leading towards practical implementation of
      this technique. The review also brings out the scopes of laser speckle-based
      analysis in various medical applications.

PMID- 22476713
TI  - Optimal features for online seizure detection.
AB  - This study identifies characteristic features in scalp EEG that simultaneously
      give the best discrimination between epileptic seizures and background EEG in
      minimally pre-processed scalp data; and have minimal computational complexity to
      be suitable for online, real-time analysis. The discriminative performance of 65
      previously reported features has been evaluated in terms of sensitivity,
      specificity, area under the sensitivity-specificity curve (AUC), and relative
      computational complexity, on 47 seizures (split in 2,698 2 s sections) in over
      172 h of scalp EEG from 24 adults. The best performing features are line length
      and relative power in the 12.5-25 Hz band. Relative power has a better seizure
      detection performance (AUC = 0.83; line length AUC = 0.77), but is calculated
      after the discrete wavelet transform and is thus more computationally complex.
      Hence, relative power achieves the best performance for offline detection, whilst
      line length would be preferable for online low complexity detection. These
      results, from the largest systematic study of seizure detection features, aid
      future researchers in selecting an optimal set of features when designing
      algorithms for both standard offline detection and new online low computational
      complexity detectors.

PMID- 22476714
TI  - Gastrostomy insertion in the 21st century: PEG or laparoscopic? Report from a
      large single-centre series.
AB  - PURPOSE: To determine whether laparoscopic-assisted gastrostomy (LAG) has
      superseded percutaneous endoscopic gastrostomy (PEG) based on the clinical
      outcomes. METHODS: A retrospective study was undertaken for the period January 06
      December 09. Demographic and clinical outcomes were recorded and the two groups
      were compared. RESULTS: 164 patients were studied (PEG, n = 107; LAG, n = 57).
      93.5 % of PEG patients required two general anaesthetics compared with 8 % of LAG
      patients. Median time to using the gastrostomy was 24 (range 0-168) h in PEG and
      0 (0-96) h in LAG patients (p < 0.001). Major complications occurred in 15/107
      (14 %) of PEG and 2/57 (3.5 %) of LAG patients (p = 0.05). Re-operation rate
      following complications was 18/107 (16.8 %) for PEG and 3/57 (5.2 %) for LAG (p =
      0.05). Minor complications arose in 41/107 (38 %) of PEG and 32/57 (56 %) of LAG
      (p = 0.05). Post-operative hospital stay was 2 (1-40) days for PEG and 2 (0-20)
      days for LAG (p = 0.01). The day-case rate was 0/107 for PEG and 5/57 (9 %) for
      LAG. There was no gastrostomy-related mortality in the series. CONCLUSION: LAG
      requires fewer anaesthetics, is associated with shorter time to feeding,
      shortened hospital stay and has a reduced risk of major complications. LAG is a
      very good alternative to the PEG in children.

PMID- 22476715
TI  - HIV and mitochondria: more than just drug toxicity.

PMID- 22476716
TI  - Which new diagnostics for tuberculosis, and when?
AB  - Recently, new diagnostic tools for tuberculosis detection and resistance testing
      have become available. The World Health Organization endorses new tuberculosis
      diagnostics by using the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) process. This endorsement process takes place when limited
      evidence beyond test accuracy is available. There is a need to provide guidance
      to tuberculosis programs about which new diagnostics to scale up and how best to
      position them in diagnostic algorithms. To speed adoption of new diagnostics for
      tuberculosis, the policy recommendation process should be revised to consist of 2
      steps: technical recommendation and programmatic recommendation. Technical
      recommendation would follow the GRADE process and be based on accuracy with
      limited cost and feasibility data, while programmatic recommendation would
      include patient-important outcomes, cost-effectiveness when implemented under
      routine conditions, and factors critical to successful scale-up. The evidence for
      both steps should be systematically collected, but each requires different study
      designs.

PMID- 22476717
TI  - HIV infection and antiretroviral therapy have divergent effects on mitochondria
      in adipose tissue.
AB  - BACKGROUND: Although human immunodeficiency virus (HIV) infection and
      antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and
      function, comprehensive evaluations of their effects on mitochondria in muscle,
      adipose tissue, and blood cells are limited. METHODS: Mitochondrial DNA
      quantification, mitochondrial genome sequencing, and gene expression analysis
      were performed on muscle, adipose tissue, and peripheral blood mononuclear cell
      (PBMC) samples from untreated HIV-positive patients, HIV-positive patients
      receiving nucleoside reverse transcriptase inhibitor (NRTI)-based ART, and HIV
      negative controls. RESULTS: The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was
      increased in untreated HIV-infected patients (ratio, 353) and decreased in those
      receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both
      comparisons); the difference between the 2 HIV-infected groups was also
      significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose
      tissue correlated with the level of activation (CD38+ /HLA-DR+) for CD4+ and CD8+
      lymphocytes. No significant differences in mtDNA content were noted in muscle or
      PMBCs among groups. Exploratory DNA microarray analysis identified differential
      gene expression between patient groups, including a subset of adipose tissue
      genes. CONCLUSIONS: HIV infection and ART have opposing effects on mtDNA content
      in adipose tissue; immune activation may mediate the effects of HIV, whereas
      NRTIs likely mediate the effects of ART.

PMID- 22476718
TI  - Clinical research and development of tuberculosis diagnostics: moving from silos
      to synergy.
AB  - The development, evaluation, and implementation of new and improved diagnostics
      have been identified as critical needs by human immunodeficiency virus (HIV) and
      tuberculosis researchers and clinicians alike. These needs exist in international
      and domestic settings and in adult and pediatric populations. Experts in
      tuberculosis and HIV care, researchers, healthcare providers, public health
      experts, and industry representatives, as well as representatives of pertinent US
      federal agencies (Centers for Disease Control and Prevention, Food and Drug
      Administration, National Institutes of Health, United States Agency for
      International Development) assembled at a workshop proposed by the Diagnostics
      Working Group of the Federal Tuberculosis Taskforce to review the state of
      tuberculosis diagnostics development in adult and pediatric populations.

PMID- 22476719
TI  - Evaluation of tuberculosis diagnostics in children: 2. Methodological issues for
      conducting and reporting research evaluations of tuberculosis diagnostics for
      intrathoracic tuberculosis in children. Consensus from an expert panel.
AB  - Confirming the diagnosis of childhood tuberculosis is a major challenge. However,
      research on childhood tuberculosis as it relates to better diagnostics is often
      neglected because of technical difficulties, such as the slow growth in culture,
      the difficulty of obtaining specimens, and the diverse and relatively nonspecific
      clinical presentation of tuberculosis in this age group. Researchers often use
      individually designed criteria for enrollment, diagnostic classifications, and
      reference standards, thereby hindering the interpretation and comparability of
      their findings. The development of standardized research approaches and
      definitions is therefore needed to strengthen the evaluation of new diagnostics
      for detection and confirmation of tuberculosis in children. In this article we
      present consensus statements on methodological issues for conducting research of
      Tuberculosis diagnostics among children, with a focus on intrathoracic
      tuberculosis. The statements are complementary to a clinical research case
      definition presented in an accompanying publication and suggest a phased approach
      to diagnostics evaluation; entry criteria for enrollment; methods for
      classification of disease certainty, including the rational use of culture within
      the case definition; age categories and comorbidities for reporting results; and
      the need to use standard operating procedures. Special consideration is given to
      the performance of microbiological culture in children and we also recommend for
      alternative methodological approaches to report findings in a standardized manner
      to overcome these limitations are made. This consensus statement is an important
      step toward ensuring greater rigor and comparability of pediatric tuberculosis
      diagnostic research, with the aim of realizing the full potential of better tests
      for children.

PMID- 22476720
TI  - Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges,
      and priority needs.
AB  - Tuberculosis was declared a global emergency by the World Health Organization
      (WHO) in 1993. Following the declaration and the promotion in 1995 of directly
      observed treatment short course (DOTS), a cost-effective strategy to contain the
      tuberculosis epidemic, nearly 7 million lives have been saved compared with the
      pre-DOTS era, high cure rates have been achieved in most countries worldwide, and
      the global incidence of tuberculosis has been in a slow decline since the early
      2000s. However, the emergence and spread of multidrug-resistant (MDR)
      tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently,
      totally drug-resistant tuberculosis pose a threat to global tuberculosis control.
      Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for
      drug susceptibility testing are inadequate in most tuberculosis-endemic
      countries, especially in Africa; thus diagnosis is missed, routine surveillance
      is not implemented, and the actual numbers of global drug-resistant tuberculosis
      cases have yet to be estimated. This exposes an ominous situation and reveals an
      urgent need for commitment by national programs to health system improvement
      because the response to MDR tuberculosis requires strong health services in
      general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate
      patient management within resource-poor national tuberculosis programs, reducing
      treatment efficacy and increasing the cost of treatment to the extent that it
      could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite
      nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis
      specific activity, has the country response to the drug-resistant tuberculosis
      epidemic been so ineffectual? The current dilemmas, unanswered questions,
      operational issues, challenges, and priority needs for global drug resistance
      screening and surveillance, improved treatment regimens, and management of
      outcomes and prevention of DR tuberculosis are discussed.

PMID- 22476721
TI  - Health and social adjustment of homeless older adults with a mental illness.
AB  - OBJECTIVE: To better inform treatment strategies, this study compared mental
      health, substance use, physical health, and social support among young, middle
      aged, and older homeless adults before and after participation in intensive case
      management services. METHODS: Data were obtained from the Access to Community
      Care and Effective Services and Supports (ACCESS) public database. Young (age 18
      to 34; N=2,469), middle-aged (age 35 to 54; N=4,358), and older (age 55 or older;
      N=408) homeless adults with a mental illness were compared on the basis of
      demographic characteristics and measures of substance use, mental and general
      medical health, and social support at baseline by using Kruskal-Wallis and chi
      square tests and at three-month and 12-month follow-ups by using mixed-model
      analysis. RESULTS: Older adults had fewer severe mental health and substance
      abuse problems than the two groups of younger adults at baseline. At 12-month
      follow-up, all age groups had improvements in housing, substance use, and
      psychiatric symptoms, but rates of psychiatric symptoms had improved the most
      among young adults, and their scores for psychiatric symptoms were the lowest on
      average of any group. Compared with older adults, adults in the younger groups
      showed greater decreases in substance use. CONCLUSIONS: Older homeless adults
      appeared to follow a different treatment trajectory than their younger
      counterparts, possibly because of lower severity of mental illness at baseline,
      and may need specific interventions to address their unique pathways to
      homelessness.

PMID- 22476722
TI  - Can high psychological job demands, low decision latitude, and high job strain
      predict disability pensions? A 12-year follow-up of middle-aged Swedish workers.
AB  - OBJECTIVES: The aim of this study was to investigate whether job strain,
      psychological demands, and decision latitude are independent determinants of
      disability pension rates over a 12-year follow-up period. METHODS: We studied
      3,181 men and 3,359 women, all middle-aged and working at least 30 h per week,
      recruited from the general population of Malmo, Sweden, in 1992. The
      participation rate was 41 %. Baseline data include sociodemographics, the Job
      Content Questionnaire, lifestyle, and health-related variables. Disability
      pension information was obtained through record linkage from the National Health
      Insurance Register. RESULTS: Nearly 20 % of the women and 15 % of the men were
      granted a disability pension during the follow-up period. The highest quartile of
      psychological job demands and the lowest quartile of decision latitude were
      associated with disability pensions when controlling for age, socioeconomic
      position, and health risk behaviours. In the final model, with adjustment also
      for health indicators and stress from outside the workplace, the hazard ratios
      for high strain jobs (i.e. high psychological demands in combination with low
      decision latitude) were 1.5 in men (95 % CI, 1.04-2.0) and 1.7 in women (95 % CI,
      1.3-2.2). Stratifying for health at baseline showed that high strain tended to
      affect healthy but not unhealthy men, while this pattern was reversed in women.
      CONCLUSIONS: High psychological demands, low decision latitude, and job strain
      were all confirmed as independent risk factors for subsequent disability
      pensions. In order to increase chances of individuals remaining in the work
      force, interventions against these adverse psychosocial factors appear
      worthwhile.

PMID- 22476723
TI  - Contractility in type III cochlear fibrocytes is dependent on non-muscle myosin
      II and intercellular gap junctional coupling.
AB  - The cochlear spiral ligament is a connective tissue that plays diverse roles in
      normal hearing. Spiral ligament fibrocytes are classified into functional sub
      types that are proposed to carry out specialized roles in fluid homeostasis, the
      mediation of inflammatory responses to trauma, and the fine tuning of cochlear
      mechanics. We derived a secondary sub-culture from guinea pig spiral ligament, in
      which the cells expressed protein markers of type III or "tension" fibrocytes,
      including non-muscle myosin II (nmII), alpha-smooth muscle actin (alphasma),
      vimentin, connexin43 (cx43), and aquaporin-1. The cells formed extensive stress
      fibers containing alphasma, which were also associated intimately with nmII
      expression, and the cells displayed the mechanically contractile phenotype
      predicted by earlier modeling studies. cx43 immunofluorescence was evident within
      intercellular plaques, and the cells were coupled via dye-permeable gap
      junctions. Coupling was blocked by meclofenamic acid (MFA), an inhibitor of cx43
      containing channels. The contraction of collagen lattice gels mediated by the
      cells could be prevented reversibly by blebbistatin, an inhibitor of nmII
      function. MFA also reduced the gel contraction, suggesting that intercellular
      coupling modulates contractility. The results demonstrate that these cells can
      impart nmII-dependent contractile force on a collagenous substrate, and support
      the hypothesis that type III fibrocytes regulate tension in the spiral ligament
      basilar membrane complex, thereby determining auditory sensitivity.

PMID- 22476725
TI  - Fractionation of Sb and As in soil and sludge samples using different continuous
      flow extraction techniques.
AB  - The fractionation of Sb and As in soil and sludge samples had been comparably
      studied using two continuous-flow systems: a microcolumn (MC) and a rotating
      coiled column (RCC). The leachants were applied in correspondence with a five
      step sequential extraction scheme addressing water-soluble, non-specifically
      sorbed, specifically sorbed, and bound to amorphous and crystalline Fe/Al oxide
      fractions of Sb and As. Inductively coupled plasma atomic emission spectroscopy
      was applied to determine antimony, arsenic, and major elements in the effluent
      and in the residual fractions after their digestion. Resemblances and
      discrepancies of the two methods were evaluated by the fractionation of Sb and As
      in forest soil, river sludge, and dumped waste (soil) samples. For the forest
      soil sample, which is very poor in organic matter, RCC and MC extractions yielded
      similar quantitative values of As and Sb contents in individual leachable
      fractions. However, for the river sludge sample with a moderate concentration of
      C (org) (3.3 %), the results obtained by both continuous-flow methods are in
      satisfactory agreement. RCC extraction enabled water-soluble and non-specifically
      sorbed As fractions to be recovered, whereas after MC leaching, these
      environmentally relevant forms of As were not detected. For the soil rich in
      organic matter (C(org) = 11.5 %), the discrepancy between the data of RCC and MC
      fractionations is significant. RCC extraction provides about six times higher
      recoveries of As and Sb bound to amorphous Fe/Al oxides. More efficient leaching
      of As and Sb in RCC may be attributed to the migration of organic-rich particles
      with low density inside the column that might enhance the mixing of the solid and
      liquid phases.

PMID- 22476724
TI  - Effects of frequency discrimination training on tinnitus: results from two
      randomised controlled trials.
AB  - That auditory perceptual training may alleviate tinnitus draws on two
      observations: (1) tinnitus probably arises from altered activity within the
      central auditory system following hearing loss and (2) sound-based training can
      change central auditory activity. Training that provides sound enrichment across
      hearing loss frequencies has therefore been hypothesised to alleviate tinnitus.
      We tested this prediction with two randomised trials of frequency discrimination
      training involving a total of 70 participants with chronic subjective tinnitus.
      Participants trained on either (1) a pure-tone standard at a frequency within
      their region of normal hearing, (2) a pure-tone standard within the region of
      hearing loss or (3) a high-pass harmonic complex tone spanning a region of
      hearing loss. Analysis of the primary outcome measure revealed an overall
      reduction in self-reported tinnitus handicap after training that was maintained
      at a 1-month follow-up assessment, but there were no significant differences
      between groups. Secondary analyses also report the effects of different domains
      of tinnitus handicap on the psychoacoustical characteristics of the tinnitus
      percept (sensation level, bandwidth and pitch) and on duration of training. Our
      overall findings and conclusions cast doubt on the superiority of a purely
      acoustic mechanism to underpin tinnitus remediation. Rather, the nonspecific
      patterns of improvement are more suggestive that auditory perceptual training
      affects impact on a contributory mechanism such as selective attention or
      emotional state.

PMID- 22476726
TI  - Peer attachment: a meta-analytic review of gender and age differences and
      associations with parent attachment.
AB  - In adolescence, peers represent key actors within individual social network.
      Given the relevance of peer connections and the growing literature examining
      them, the purpose of this article was to review, through a meta-analytic
      approach, studies on adolescent and youth peer relationships within the
      theoretical framework of attachment. First, we synthesized results of 44 studies
      focused on relationships between parent and peer attachment. Second, we
      summarized findings of 54 studies reporting gender differences on peer
      attachment. Third, we computed an overall effect for age differences on peer
      attachment documented in 19 studies. Main findings highlighted that parent
      attachment is moderately correlated to peer attachment; that females were
      significantly more attached to their peers than males; and that the correlation
      between age and peer attachment was not significant. This set of findings was
      confirmed examining both overall peer attachment as well as specific dimensions
      of attachment, such as trust and communication. Furthermore, since a significant
      heterogeneity was found across studies, we tested the effects of various
      categorical (i.e., year and language of publication, country, attachment measure)
      and continuous (i.e., mean age and percentage of females of the sample, number of
      items of the peer attachment scale) moderators related to characteristics of the
      study samples and designs. Implications of these findings for future research are
      discussed. A focus on cultural dimensions and on peer attachment processes would
      be worthwhile to address relevant research questions: How do peer relationships
      progressively become mature attachment relationships? How is this process shaped
      for individuals with different parent attachment histories?

PMID- 22476727
TI  - Religiosity profiles of American youth in relation to substance use, violence,
      and delinquency.
AB  - Relatively little is known in terms of the relationship between religiosity
      profiles and adolescents' involvement in substance use, violence, and
      delinquency. Using a diverse sample of 17,705 (49 % female) adolescents from the
      2008 National Survey on Drug Use and Health, latent profile analysis and
      multinomial regression are employed to examine the relationships between latent
      religiosity classes and substance use, violence, and delinquency. Results
      revealed a five class solution. Classes were identified as religiously disengaged
      (10.76 %), religiously infrequent (23.59 %), privately religious (6.55 %),
      religious regulars (40.85 %), and religiously devoted (18.25 %). Membership in
      the religiously devoted class was associated with the decreased likelihood of
      participation in a variety of substance use behaviors as well as decreases in the
      likelihood of fighting and theft. To a lesser extent, membership in the religious
      regulars class was also associated with the decreased likelihood of substance use
      and fighting. However, membership in the religiously infrequent and privately
      religious classes was only associated with the decreased likelihood of marijuana
      use. Findings suggest that private religiosity alone does not serve to buffer
      youth effectively against involvement in problem behavior, but rather that it is
      the combination of intrinsic and extrinsic adolescent religiosity factors that is
      associated with participation in fewer problem behaviors.

PMID- 22476728
TI  - Genetic and environmental influences on the association between pubertal
      maturation and internalizing symptoms.
AB  - The literature consistently shows an association between pubertal maturation and
      internalizing problems in girls. The association for boys is less clear. The
      present study examines genetic and environmental influences on the association
      between pubertal maturation and internalizing problems for boys and girls in two
      primarily Caucasian adolescent twin/sibling studies: The Swedish Twin study of
      CHild and Adolescent Development (706 same-sex twin pairs aged 13-14, M = 13.7
      years, 50 % female), and the Nonshared Environment in Adolescent Development
      sample (US-based, 687 same-sex twin/sibling pairs aged 10-18, M = 13.6 years, 47
      % female). For girls, more advanced pubertal maturation was associated modestly
      with more internalizing problems, and that association was entirely explained by
      shared environmental influences. For boys, the association between pubertal
      maturation and internalizing problems was weak and inconsistent. Results for
      girls were remarkably consistent across samples. Findings suggest that nongenetic
      mechanisms mediate the association between pubertal maturation and internalizing
      problems. Findings have implications for intervention such that environmental
      influences shared by twins/siblings may provide the best targets for intervention
      strategies designed to minimize the potential negative effects of pubertal
      maturation on internalizing symptoms in girls.

PMID- 22476729
TI  - Early respiratory morbidity in a multicultural birth cohort: the Generation R
      Study.
AB  - Ethnic disparities in the prevalence of asthma symptoms in children have been
      described. We evaluated to what extent the association between ethnic background
      and respiratory symptoms during the first 2 years of life could be explained by
      the mediating effect of risk factors for respiratory morbidity. The Generation R
      Study is a multiethnic, population-based birth cohort study. Pre and postnatal
      risk factors for respiratory morbidity were prospectively assessed by
      questionnaires. Information about ethnicity was available for 5,684 infants. The
      associations between ethnic background and lower respiratory symptoms at 12 and
      24 months were evaluated with log-binomial regression models. Relative risks and
      95 % confidence intervals (RR [95 % CI]) were computed for Cape Verdean,
      Moroccan, Antillean, Surinamese and Turkish ethnicity with Dutch ethnicity as the
      reference category. We found an increased risk of lower respiratory symptoms at
      24 months in Antillean infants (1.32 [95 % CI 1.12-1.57]) that was mediated by
      early postnatal exposures (pets keeping, siblings, breastfeeding, daycare
      attendance, smoke exposure). Turkish infants also had an increased risk of lower
      respiratory symptoms at 12 and 24 months (1.14 [95 % CI 1.02-1.27] and 1.21 [95 %
      CI 1.07-1.38], respectively), partly explained by previous morbidity (eczema,
      infections and upper respiratory symptoms). There were no differences for Cape
      Verdean, Moroccan or Surinamese, as compared to Dutch infants. Hence, ethnic
      background was associated with respiratory symptoms during the first 2 years of
      life and this association was largely explained by mediating effects of known pre
      and postnatal risk factors for respiratory morbidity.

PMID- 22476730
TI  - Feasibility of emergency laparoscopic colectomy for children with acute colonic
      perforations and fibropurulent peritonitis.
AB  - BACKGROUND: Several studies have demonstrated that laparoscopic surgery is safe
      and effective for urgent and emergent colectomy in adulthood. The aim of the
      present study was to evaluate the feasibility of laparoscopic colectomy for
      children in emergent settings. METHODS: Between March 2008 and August 2011, 10
      consecutive children with acute colonic perforations and fibropurulent
      peritonitis secondary to infectious colitis underwent emergency laparoscopic
      colectomy. Simultaneously, we reviewed and recorded the same data from another
      consecutive 10 patients who underwent standard laparotomy between November 2004
      and February 2008. The two groups were compared with regard to operative time,
      length of hospital stay (LOS), and complications. RESULTS: The gender, age, body
      weight, serum C-reactive protein, number of involved bowel segments, operative
      time, and LOS were not significantly different (P = 0.36, 0.50, 0.33, 0.62, 0.81,
      0.14 and 0.23, respectively). In the laparoscopy group, one patient required
      conversion to open surgery because of extensive bowel involvement, and another
      patient with solitary colonic perforation required reoperation for anastomostic
      leakage. However, patients who underwent laparotomy had a higher incidence of
      later complications, including wound infection, incisional hernia, and adhesion
      ileus (P = 0.03, 0.06, and 0.03, respectively) and thus required more additional
      unplanned operations (P = 0.05). CONCLUSIONS: Emergency laparoscopic surgery is
      technically feasible in most children with acute colonic perforations and
      fibropurulent peritonitis. However, extensive intestinal involvement with
      multiple perforations should be an indication for converting to open surgery.

PMID- 22476731
TI  - Gliosarcoma with osseous tissue: an occasional metaplastic component.
AB  - Glioosarcomas represent a rare entity of intrinsic CNS neoplasms consisting of
      glial and sarcomatous elements; they account for 2 % of glioblastomas. There have
      been few reports of metaplastic osseous transformation in gliosarcomas. Here we
      report a rare case of gliosarcoma with metaplastic osteoid in a 57-year-old male
      patient. Magnetic resonance imaging revealed a large solid cystic heterogeneous
      mass lesion in the left temporal lobe with peri-tumoral oedema and areas of
      calcification. Histology revealed a grade IV tumour with neoplastic glial and
      mesenchymal components with myxoid change and areas of necrosis. The sarcomatous
      areas contained regions of benign osteoid formation. The histogenesis of the
      osseous element in gliosarcomas is not well understood, and could be a result of
      a metaplastic change or divergent differentiation from a common progenitor cell.
      The osseous tissue may be in the form of newly formed osteoid, benign bone tissue
      formation with lacunae and osteoblastic rimming, or unequivocally malignant
      tissue resembling an osteosarcoma.

PMID- 22476732
TI  - Models of highly pathogenic avian influenza epidemics in commercial poultry
      flocks in Nigeria and Ghana.
AB  - State-scale and premises-scale gravity models for the spread of highly pathogenic
      avian influenza (H5N1) in Nigeria and Ghana were used to provide a basis for risk
      maps for future epidemics and to compare and rank plausible culling and
      vaccination strategies for control. Maximum likelihood methods were used to fit
      the models to the 2006-2007 outbreaks. The sensitivity and specificity of the
      state-scale model-generated probabilities that any given state would be involved
      in an epidemic were each 57 %. The premises-based model indicated that reactive,
      countrywide vaccination strategies, in which the order in which flocks are
      vaccinated was strictly determined by known risk factors for infection, were more
      effective in reducing the final size of the epidemic and the epidemic impact than
      vaccinating flocks at random or ring vaccination. The model suggests that an
      introduction of highly pathogenic avian influenza (H5N1) into Ghana had a high
      chance (84 %) of causing a major outbreak. That this did not happen was most
      probably a result of the very swift Ghanaian response to news of the first
      introductions.

PMID- 22476733
TI  - Effect of feeding different proportions of groundnut haulms (Arachis hypogaea)
      and cluster bean straw (Cyamopsis tetragonoloba) on nutrient utilisation and
      serum biochemical parameters in dromedary camels.
AB  - The effect of feeding different proportions of groundnut haulms (Arachis
      hypogaea) and cluster bean straw (Cyamopsis tetragonoloba) on nutrient
      digestibility, nutritive value, nutrient intake and serum biochemical parameters
      was studied using nine male dromedary camels of Bikaneri breeds (637.5 kg average
      body weight; 8-9 years of age). Groundnut haulms (GNH) and cluster bean straw
      (CBS) were fed in one of three ratios, 75:25, 50:50 and 25:75 in treatments T(1),
      T(2) and T(3), respectively. In all treatments, concentrate mixture was fed as
      per requirement of the camels. The groundnut haulms were more nutritive as
      compared to the cluster bean straw. The nutrient digestibility of dry matter,
      organic matter, crude protein (CP), crude fibre and acid detergent fibre was
      better in T(1) than T(2) and T(3). Likewise, the CP, digestible crude protein and
      total digestible nutrient contents were significantly higher in T(1) followed by
      T(2) and T(3). There was non-significant affect on average daily gain of camels.
      However, dry matter intake, digestible crude protein intake and total digestible
      nutrients were better in T(1) as compared to T(2) and T(3). The total water
      intake per kilogram of dry matter intake (litres) was 2.98, 2.89 and 2.68,
      respectively, in T(1), T(2) and T(3). The camels in all the treatments were in
      positive nitrogen, calcium and phosphorus balance. The treatments had a
      significant effect on serum biochemical parameters like glucose, cholesterol,
      aspartate transaminase and creatinine. The results may conclude that feeding of
      higher proportion of groundnut haulms as compared to cluster bean straw has
      pronounced improvement in nutritional utilisation by the camels.

PMID- 22476734
TI  - Effect of L-arginine methyl ester (L-NAME) on hormonal profile and estrous cycle
      length in buffaloes (Bubalus bubalis).
AB  - The present study was undertaken to evaluate the effect of L-arginine methyl
      ester (L-NAME), a nitric oxide synthase inhibitor on serum nitric oxide,
      progesterone, estradiol profiles and estrous cycle length in buffaloes. Murrah
      buffaloes (n = 16) exhibiting regular estrous cycles were randomly allocated to
      two groups of eight animals. In the treatment group, buffaloes were administered
      400 mg/h L-NAME over 2 h (total dose = 800 mg) via the coccygeal artery and the
      aorta abdominalis on day 15 of the estrous cycle. In the control group, normal
      saline was infused on the same day of the cycle by the same route. Blood samples
      were collected every 4 h on days 15 and 16, and once daily from days 17 to 21 of
      the estrous cycle for the assay of progesterone, estradiol and nitric oxide. L
      NAME treatment significantly (p < 0.05) reduced serum nitric oxide concentration
      from 4 h of day 15 until day 20 of the cycle. Serum progesterone concentration
      increased significantly (p < 0.05) between 0 and 20 h post treatment on day 15.
      The estrous cycle length was 19.8 +/- 0.36 and 23.6 +/- 0.17 days for control and
      treated group buffalo (p < 0.05), respectively. It was concluded that treatment
      of buffalo with L-NAME in the late luteal phase of the estrous cycle inhibited
      serum nitric oxide concentration resulting in increased progesterone production
      and extension of the effective life of the corpus luteum, thus prolonging the
      estrous cycle length.

PMID- 22476735
TI  - Influence of different supplements and sugarcane (Saccharum officinarum L.)
      cultivars on intake, digestible variables and methane production of dairy heifers
      under tropical conditions.
AB  - The sulphur hexafluoride (SF(6)) gas tracer method was used to measure methane
      (CH(4)) production of crossbred (3/4 Holstein x Zebu) dairy heifers fed two types
      of sugarcane (Saccharum officinarum L.; cultivar IAC-862480 (CC1) or cultivar IAC
      873184 (CC2)) and supplemented with urea or concentrate. The study was performed
      at Embrapa Southeast Cattle, Sao Carlos, SP, Brazil, using a completely
      randomised design. Differences between treatments were significant for
      digestibility of dry matter, organic matter and energy. When animals were
      supplemented with urea differences between sugarcane cultivars did occur for NDF
      consumption, but not for daily methane production. This suggest that variation in
      chemical composition of sugarcane did not affect bovine ruminal CH(4) emissions.
      Concentrate inclusion in animal diet increased digestible organic matter intake,
      improving the nutrient intake by animals, but did not reduce CH(4) production
      expressed as a percentage of gross energy intake.

PMID- 22476736
TI  - Gum chewing enhances early recovery of bowel function following transperitoneal
      abdominal aortic surgery.
AB  - BACKGROUND AND PURPOSE: Postoperative bowel dysfunction is still a major unsolved
      problem following transperitoneal abdominal aortic surgery. We conducted this
      study to establish if gum chewing during the postoperative period promotes
      recovery of bowel function following abdominal aortic surgery. METHODS: The
      subjects were 44 patients who underwent elective abdominal aortic surgery. The
      patients were allocated to a control group (n = 21), who received standard
      postoperative care, or a "gum group" (n = 23), who received standard
      postoperative care and were also given gum to chew three times a day from
      postoperative day (POD) 0-5. RESULTS: The patient characteristics,
      intraoperative, and postoperative care were equivalent in both groups. Flatus was
      passed on POD 1.49 in the gum group and on POD 2.35 in the control group (P =
      .0004) and the time to oral intake was 3.09 days in the gum group and 3.86 days
      in the control group (P = .023). The number of days to full mobilization in the
      hospital room was 3.35 versus 5.59 for the gum and control groups, respectively
      (P < .0001). CONCLUSIONS: Gum chewing enhances early recovery of bowel function
      following transperitoneal abdominal aortic surgery. Moreover, it is a
      physiologically sound, safe, and an inexpensive part of the postoperative care.

PMID- 22476737
TI  - A novel fatty acid, 12,17-dimethyloctadecanoic acid, from the extremophile
      Thermogemmatispora sp. (Strain T81).
AB  - The major fatty acids of a novel species of Thermogemmatispora sp. (strain T81)
      from the phylum Chloroflexi were identified as i18:0 (42.8 % of total fatty
      acids), i19:0 (9.7 %), and i17:0 (5.9 %). Also observed was a number of
      unidentified fatty acids, including a major acid (16.3 %) with ECL of 19.04
      (BP1), and 18.76 (TG-WAXMS A). GCMS revealed that this compound is a saturated 20
      carbon atom fatty acid. (1)H- and (13)C-NMR, with (1)H-(1)H-COSY and (1)H-(13)C
      HSQC experiments suggested the structure of dimethyl octadecanoic acid with iso
      branching, and an extra middle-chain methyl group. A pyrrolidide derivative
      demonstrated the characteristic gaps in GCMS indicating methyl branching at C12
      and C17, which was eventually confirmed by a (1)H-(13)C-HSQC-TOCSY experiment.
      This 12,17-dimethyloctadecanoic acid has not been previously detected or
      described in these organisms. However, a recent description of a phylogenetically
      related species of Thermogemmatispora (Yabe et al., Int J Syst Evol Microbiol
      61:903-910, 2010), noted an unidentified 20:0 fatty acid with matching GC
      behavior and GCMS data to that of strain T81. These data suggest that
      Thermogemmatispora share an ability to synthesize the same fatty acid. A number
      of other dimethyl-branched fatty acids, namely 8,14-diMe 15:0; 12,15-diMe 16:0;
      10,15-diMe 16:0; 12,16-diMe 17:0; 10,16-diMe 17:0; 12,17-diMe 18:0; 12,18-diMe
      19:0; 14,19-diMe 20:0, were also identified in strain T81.

PMID- 22476738
TI  - Empirical research on moral distress: issues, challenges, and opportunities.
AB  - Studying a concept as complex as moral distress is an ongoing challenge for those
      engaged in empirical ethics research. Qualitative studies of nurses have
      illuminated the experience of moral distress and widened the contours of the
      concept, particularly in the area of root causes. This work has led to the
      current understanding that moral distress can arise from clinical situations,
      factors internal to the individual professional, and factors present in unit
      cultures, the institution, and the larger health care environment. Corley et al.
      (2001) was the first to publish a quantitative measure of moral distress, and her
      scale has been adapted for use by others, including studies of other disciplines
      (Hamric and Blackhall 2007; Schwenzer and Wang 2006). Other scholars have
      proposed variations on Jameton's core definition (Sporrong et al. 2006, 2007),
      developing measures for related concepts such as moral sensitivity (Lutzen et al.
      2006), ethics stress (Raines 2000), and stress of conscience (Glasberg et al.
      2006). The lack of consistency and consensus on the definition of moral distress
      considerably complicates efforts to study it. Increased attention by researchers
      in disciplines other than nursing has taken different forms, some problematic.
      Cultural differences in the role of the nurse and understanding of actions that
      represent threats to moral integrity also challenge efforts to build a cohesive
      research-based understanding of the concept. In this paper, research efforts to
      date are reviewed. The importance of capturing root causes of moral distress in
      instruments, particularly those at unit and system levels, to allow for
      interventions to be appropriately targeted is highlighted. In addition, the issue
      of studying moral distress and interaction over time with moral residue is
      discussed. Promising recent work is described along with the potential these
      approaches open for research that can lead to interventions to decrease moral
      distress. Finally, opportunities for future research and study are identified,
      and recommendations for moving the research agenda forward are offered.

PMID- 22476739
TI  - [Standardised scoring of a multi-parametric 3-T MRI for a targeted MRI-guided
      prostate biopsy].
AB  - BACKGROUND: The use of multi-parametric MRI and MRI-guided biopsy for the
      detection of prostate cancer is rapidly increasing. This is a pilot study to
      evaluate the consensus-based international MRI scoring system as decision
      criterion for targeted MRI-guided prostate biopsy. MATERIAL AND METHODS: After a
      multi-parametric 3-T MRI (T2-weighted imaging, diffusion-weighted imaging, and
      dynamic contrast-enhanced MRI) in 23 consecutive patients a total of 47 lesions
      were scored according to a 5-point scale for each MRI sequence. A total score of
      >= 10 points was considered to be suspicious for prostate cancer. All 47 lesions
      were histologically assessed after MRI-guided biopsy. RESULTS: At the cut-off
      score of 10 points, sensitivity, specificity, negative predictive value and
      positive predictive value of multi-parametric MRI were 94.1, 43.3, 92.9 and
      48.5%, respectively. CONCLUSIONS: A standardised scoring of lesions on multi
      parametric MRI is feasible. The cut-off value leads to excellent values for
      sensitivity and negative predictive value. The values for specificity and
      positive predictive value are modest. Lesions with a total score <10 points are
      very unlikely to be malignant.

PMID- 22476740
TI  - [Choline PET/CT in the diagnosis of primary and recurrent prostate cancer. Are
      there evidence-based indications?].
AB  - Overdiagnosis and resulting overtreatment in prostate cancer are under intensive
      discussion both in the urologic communities and in the public media. Sensitive
      and specific diagnostic modalities could be one step forward to overcome this
      problem. Choline PET/CT provides fusion imaging that combines
      anatomical/morphological information with metabolic/functional data. Despite
      promising preclinical data and interesting initial clinical results, this cost
      intensive and logistically demanding technology has not yet found its way into
      routine clinical practice; the German and European guideline recommendations are
      careful and reluctant. This review has the goal to give an overview of the recent
      data both on initial diagnosis and on staging/diagnosis for biochemical
      recurrence by choline PET/CT and to summarize the possible role of this
      innovative technology in the future, if adequate research projects can be
      realized.

PMID- 22476741
TI  - [The urological Dyna-CT. Urological cross-sectional imaging on a newly developed
      urological intervention table].
AB  - BACKGROUND: The development of a new urological intervention table now enables
      the application of an Artis zee ceiling Dyna-CT (Siemens, Erlangen, Germany) for
      interventional cross-sectional imaging and 3-D reconstruction of the urinary
      tract in the prone and supine positions (urological Dyna-CT). MATERIALS AND
      METHODS: We tested the feasibility of the urological Dyna-CT with the newly
      developed urological intervention table. The system was moved five times to
      enable 3-D reconstruction of the urinary tract of a test person in the prone and
      in supine positions. RESULTS: Handling of the free floating table is easily
      possible during the intervention. We found no limitation of imaging system
      movement in any position of the test person. CONCLUSION: Apart from standard
      urological imaging such as fluoroscopy, intravenous pyelography or plain
      abdominal X-ray the urological Dyna-CT enables further imaging of the urinary
      tract. Fluoroscopy sequences can be stored as videos, and 3-D reconstructions of
      the urinary tract are possible with permanent patient access for any
      intervention. Extensive tests led to the technical approval of the system in
      urology.

PMID- 22476742
TI  - [Wolfgang Knipper (1920-2005): a contribution to the series on the"Man Behind the
      Prize"].
AB  - Every year during the annual conference of the German Society of Urology, the
      Wolfgang Knipper Prize is awarded in memory of the Hamburg urologist Prof. Dr.
      med. Wolfgang Knipper to urological nursing staff who have been particularly
      active in the field of training and continuing education for nurses and medical
      assistants. Over the course of more than four decades, Professor Knipper achieved
      considerable recognition particularly for his work in continuing education for
      auxiliary personnel. He became President and Honorary President of the
      Berufsverband der deutschen Urologen e.V. (Professional Association of German
      Urologists) and an honorary member of numerous professional societies, including
      the German Society of Urology.

PMID- 22476743
TI  - ["Racial improvement" in Ravensburg].
AB  - After implementation of the Law for the Prevention of Progeny with Hereditary
      Diseases on 1 January 1934 the first enforced sterilizations were undertaken at
      the Stadtische Krankenhaus-Heilig-Geist-Spital in Ravensburg. Between April 1934
      and March 1938, 389 sterilization operations were performed. For later years no
      data is available, but it can be assumed that the total number is significantly
      greater. Patients affected were transferred to the Stadtische Krankenhaus by the
      Psychiatric Clinic Weissenau, Gertrudisheim, and the Clinic for Deaf and Dumb in
      Wilhelmsdorf. In only about half of the cases was the rationale for the
      sterilization program stated. The main reasons included: mental illness (57%),
      schizophrenia (23%), and epilepsy (6%). This was similar to the total data
      published for all of Germany.

PMID- 22476744
TI  - Parcel-based connectivity analysis of fMRI data for the study of epileptic
      seizure propagation.
AB  - The aim of this work is to improve fMRI Granger Causality Analysis (GCA) by
      proposing and comparing two strategies for defining the topology of the networks
      among which cerebral connectivity is measured and to apply fMRI GCA for studying
      epileptic seizure propagation. The first proposed method is based on information
      derived from anatomical atlas only; the other one is based on functional
      information and employs an algorithm of hierarchical clustering applied to fMRI
      data directly. Both methods were applied to signals recorded during seizures on a
      group of epileptic subjects and two connectivity matrices were obtained for each
      patient. The performances of the different parcellation strategies were evaluated
      in terms of their capability to recover information about the source and the sink
      of the network (i.e., the starting and the ending point of the seizure
      propagation). The first method allows to clearly identify the seizure onset in
      all patients, whereas the network sources are not so immediately recognizable
      when the second method was used. Nevertheless, results obtained using functional
      clustering do not contradict those obtained with the anatomical atlas and are
      able to individuate the main pattern of propagation. In conclusion, the way nodes
      are defined can influence the easiness of identification of the epileptogenic
      focus but does not produce contradictory results showing the effectiveness of
      proposed approach to formulate hypothesis about seizure propagation at least in
      the early phase of investigation.

PMID- 22476745
TI  - Treatment of acute disseminated encephalomyelitis.
AB  - OPINION STATEMENT: Acute disseminated encephalomyelitis (ADEM) is an inflammatory
      demyelinating disease, characterized by an acute onset of polyfocal central
      nervous system (CNS) deficits, including encephalopathy, demonstrating multifocal
      lesions on MRI. ADEM is typically a monophasic disorder, but recurrent and
      multiphasic courses have been described. Furthermore, an ADEM presentation has
      been reported in neuromyelitis optica (NMO) and multiple sclerosis (MS),
      particularly in younger children. CNS infections, other autoimmune diseases, and
      neurometabolic disorders may mimic ADEM at manifestation. There is no single test
      confirming the diagnosis of ADEM, and diagnosis is based upon a combination of
      clinical and radiologic features and exclusion of diseases that resemble ADEM.
      Therefore, a broad workup including infectious, immunologic, and metabolic tests,
      as well as a systematic follow-up including MRI, is indicated to establish an
      accurate diagnosis as a prerequisite for an optimized treatment approach. There
      is a lack of evidence-based, prospective clinical trial data for the management
      of ADEM. Empiric antibacterial and antiviral treatment is standard of care until
      an infectious disease process is ruled out. Based on the presumed autoimmune
      etiology of ADEM, the common treatment approach consists of intravenous
      methylprednisolone at a dosage of 20 to 30 mg/kg per day (maximum 1 g/day) for 3
      to 5 days, followed by an oral corticosteroid taper of 4 to 6 weeks. In case of
      insufficient response or contraindications to corticosteroids, intravenous
      immunoglobulin G (IVIG) at a dosage of 2 g/kg divided over 2 to 5 days is a
      therapeutic option. For severe or life-threatening cases of ADEM, plasmapheresis
      should be considered early in the disease course. Decompressive craniectomy has
      been reported as a life-saving measure for ADEM patients with intracranial
      hypertension. There is a lack of specific recommendations for the long-term
      management of recurrent and multiphasic ADEM. In children with relapsing
      demyelinating events, the diagnosis of a chronic autoimmune CNS disease like MS
      or NMO should be considered.

PMID- 22476747
TI  - New moment closures based on a priori distributions with applications to epidemic
      dynamics.
AB  - Recently, research that focuses on the rigorous understanding of the relation
      between simulation and/or exact models on graphs and approximate counterparts has
      gained lots of momentum. This includes revisiting the performance of classic
      pairwise models with closures at the level of pairs and/or triples as well as
      effective-degree-type models and those based on the probability generating
      function formalism. In this paper, for a fully connected graph and the simple SIS
      (susceptible-infected-susceptible) epidemic model, a novel closure is introduced.
      This is done via using the equations for the moments of the distribution
      describing the number of infecteds at all times combined with the empirical
      observations that this is well described/approximated by a binomial distribution
      with time dependent parameters. This assumption allows us to express higher order
      moments in terms of lower order ones and this leads to a new closure. The
      significant feature of the new closure is that the difference of the exact
      system, given by the Kolmogorov equations, from the solution of the newly defined
      approximate system is of order 1/N(2). This is in contrast with the O(1/N)
      difference corresponding to the approximate system obtained via the classic
      triple closure. The fully connected nature of the graph also allows us to
      interpret pairwise equations in terms of the moments and thus treat closures and
      the two approximate models within the same framework. Finally, the applicability
      and limitations of the new methodology is discussed in detail.

PMID- 22476748
TI  - Patterns of recurrence following complete response to regional chemotherapy for
      in-transit melanoma.
AB  - BACKGROUND: Even after complete response (CR) to regional chemotherapy for in
      transit melanoma, many patients develop recurrence. Understanding the
      probability, location, and timing of recurrences can optimize management
      strategies for this patient population. METHODS: A prospective database
      identified patients who underwent 81 first-time hyperthermic isolated limb
      perfusions (HILPs) and 133 first-time isolated limb infusions (ILIs). Response
      was defined using the response evaluation criteria in solid tumors; recurrence
      was defined as development of new disease after in-field CR. RESULTS: HILP
      exhibited a significantly higher CR rate than ILI (44 vs. 28 %, p = .01). Among
      36 HILP-CRs and 37 ILI-CRs, the 3-year recurrence rate was 65 % (95 % confidence
      interval [95 % CI]: 43-79 %) and 85 % (95 % CI: 63-94%), respectively. Median
      time to first recurrence was longer for HILP-CR than ILI-CR (23 vs. 8 months, p =
      .02). There was no statistically significant difference in median time to in
      field recurrence between HILP-CR and ILI-CR (46 vs. 25 months, p = .15), but HILP
      CR showed a longer median time to out-of-field recurrence (42 vs. 14 months, p =
      .02). Finally, the overall survival (OS) difference between HILP-CR and ILI-CR (3
      year survival: 77 vs. 54 %) did not achieve statistical significance (p = .10).
      CONCLUSIONS: In the largest series comparing patterns of recurrence, we
      demonstrate that out-of-field recurrence after CR to HILP occurs later than after
      CR to ILI, though control of in-field disease remains similar. There remains no
      statistically significant difference in overall survival after CR to the 2
      procedures.

PMID- 22476749
TI  - Recurrent amplification at 7q21.2 Targets CDK6 gene in primary myxofibrosarcomas
      and identifies CDK6 overexpression as an independent adverse prognosticator.
AB  - BACKGROUND: Myxofibrosarcoma is genetically complex and remains obscure in
      molecular determinants of clinical aggressiveness. Our prior study revealed
      recurrent gains of 7q in myxofibrosarcomas where MET and CDK6 genes displayed
      increased DNA copies. Previously, we demonstrated the implication of MET
      overexpression, prompting us to further elucidate the roles of CDK6 in
      myxofibrosarcomas. MATERIALS: On tissue microarrays, CDK6 immunoexpression was
      assessable in 77 primary tumors, 55 of which were successfully quantified for
      CDK6 and MET genes by real-time PCR using genomic DNA extracted from laser
      microdissected tumor cells. Gene status and protein expression of CDK6 were
      correlated with each other, clinicopathological variables, metastasis-free
      survival (MFS), and disease-specific survival (DSS). RESULTS: Protein
      overexpression and gene amplification of CDK6, which were detected in 21 of 77
      (27.2 %) and 13 of 55 cases (23.6 %), respectively, were highly related to each
      other (p < .001) and associated with higher grades (overexpression, p = .004;
      amplification, p = .014). There was a strong correlation between CDK6 and MET
      gene copies (p < .001, r = 0.0714). Importantly, CDK6 protein overexpression
      (MFS, p = .0002; DSS, p = .0015) and gene amplification (MFS, p = .0001; DSS, p =
      .0083) were both univariately associated with worse outcomes. Together with
      nonextremity location and AJCC stage III disease, CDK6 overexpression
      independently portended inferior MFS (p = .0015, risk ratio [RR] = 7.411). This
      aberration, along with nonextremity location, was also an independent adverse
      prognosticator of DSS (p = .0069, RR = 6.006). CONCLUSIONS: In approximately a
      quarter of primary myxofibrosarcomas, CDK6 overexpression is mostly driven by
      gene amplification on 7q, associated with adverse prognosticators, and
      independently predictive of worse outcomes, highlighting its possible causative
      role in tumor aggressiveness.

PMID- 22476750
TI  - Locoregional recurrence after mastectomy with immediate transverse rectus
      abdominis myocutaneous (TRAM) flap reconstruction.
AB  - BACKGROUND: The locoregional recurrence (LRR) rate after mastectomy is reported
      to be similar with immediate reconstruction. We aimed to identify characteristics
      of LRR after transverse rectus abdominis myocutaneous (TRAM) reconstruction.
      METHODS: We retrospectively reviewed patients undergoing immediate TRAM
      reconstruction for breast cancer who were diagnosed with LRR. RESULTS: We
      identified 18 LRR (4.6 %) in 18 of 390 patients who underwent immediate TRAM
      reconstructions for breast cancer from 1998 to 2008. The median follow-up was
      69.2 months. The mean age at time of mastectomy was 49.5 years. All LRR were
      detected by physical examination. The LRR occurred in the TRAM subcutaneous
      tissue (n = 9), five in the ipsilateral axillary lymph node and four in the
      supraclavicular lymph node. Of the 18 patients who developed LRR, 14 (77.7 %)
      presented with stage 0-1-2 and 4 (22.2 %) with stage 3 disease at the time of the
      original mastectomy. The average time for a LRR to present was 35.8 months after
      initial mastectomy and reconstruction. For patients who initially presented with
      stage 3 disease, the average time to LRR was shorter (22.9 months). Nine patients
      (50.0 %) were found to have metastatic disease at the time of the LRR, and 6
      (33.3 %) died of disease. CONCLUSIONS: All TRAM LRR were detected by routine
      physical examination by the patient or the surgeon. Our findings suggest that
      routine history and clinical breast examination of the breast reconstructed with
      a TRAM flap along with patient self-awareness are reliable in the diagnosis of
      LRR.

PMID- 22476751
TI  - Limited M1 disease: a significant prognostic factor for stage IV breast cancer.
AB  - PURPOSE: The prognosis of patients with breast cancer presenting with distant
      metastasis can vary depending on disease extent. This study evaluates a
      definition of limited M1 disease in association with survival in a cohort of
      women presenting with metastatic breast cancer. METHODS: The study cohort
      comprised 692 women referred to the BC Cancer Agency between 1996 and 2005 with
      M1 breast cancer at presentation. Limited M1 disease was defined as <5 metastatic
      lesions confined to one anatomic subsite. Extensive M1 disease was defined as >=
      5 lesions or disease in more than one subsite. Clinicopathologic and treatment
      characteristics and overall survival (OS) were compared between subjects with
      limited (n = 233) versus extensive (n = 459) M1 disease. Multivariable analysis
      was performed by Cox regression modeling. RESULTS: Median follow-up time was 1.9
      years. Five-year Kaplan-Meier OS was significantly higher in patients with
      limited compared to extensive M1 disease (29.7 vs. 13.1 %, p < 0.001). In the
      multivariable Cox regression analysis, limited M1 disease was significantly
      associated with OS (hazard ratio 0.51, 95 % confidence interval 0.40-0.66, p <
      0.001). The only patient subsets with limited M1 disease with poor 5-year OS <15
      % were patients with Eastern Cooperative Oncology Group performance status of >=
      2 or estrogen receptor-negative status. CONCLUSIONS: Limited M1 disease, defined
      as <5 metastatic lesions confined to one anatomic subsite, is a relevant
      favorable prognostic factor in patients with stage IV breast cancer. This
      definition may be used in conjunction with other clinicopathologic factors to
      select patients for more aggressive systemic and locoregional treatments.

PMID- 22476752
TI  - Cardiac angiosarcoma management and outcomes: 20-year single-institution
      experience.
AB  - PURPOSE: To identify the clinicopathologic characteristics, treatments, and
      outcomes of a series of patients with primary cardiac angiosarcoma (AS). METHODS:
      This retrospective case series was set in a tertiary referral center with a
      multidisciplinary clinic. Consecutive patients with institutionally confirmed
      pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed.
      Main outcome measures included patient demographics, tumor characteristics,
      management strategies, disease response, and survival. RESULTS: Data from 18
      patients (78 % male) were reviewed. Sixteen patients (89 %) had AS originating in
      the right atrium. At diagnosis, eight patients (44 %) had localized/locally
      advanced disease and ten patients (56 %) had metastatic disease. Initial
      treatment strategies included resection (44 %), chemotherapy (39 %), and
      radiotherapy (11 %). Of the eight patients with localized/locally advanced AS,
      two underwent macroscopically complete resection with negative microscopic
      margins, one underwent macroscopically complete resection with positive
      microscopic margins, one underwent macroscopically incomplete resection, two
      received chemotherapy followed by surgery and intraoperative radiotherapy, one
      received chemotherapy alone, and one died before planned radiotherapy. Median
      follow-up was 12 months. Median overall survival (OS) was 13 months for the
      entire cohort; median OS was 19.5 months for those presenting with
      localized/locally advanced AS and 6 months for those with metastatic disease at
      presentation (p = 0.08). Patients who underwent primary tumor resection had
      improved median OS compared with patients whose tumors remained in situ (17 vs. 5
      months, p = 0.01). CONCLUSIONS: Cardiac AS is associated with poor prognosis.
      Resection of primary tumor should be attempted when feasible, as OS may be
      improved. Nevertheless, most patients die of disease progression.

PMID- 22476753
TI  - Pathologic response to preoperative chemotherapy in colorectal liver metastases:
      fibrosis, not necrosis, predicts outcome.
AB  - BACKGROUND: Pathologic response to preoperative chemotherapy for colorectal liver
      metastases (CLM) is associated with survival after hepatectomy. Histologically,
      dominant response patterns include fibrosis, necrosis and/or acellular mucin, but
      some of these changes can appear without previous chemotherapy and their
      individual correlation with outcome is unknown. METHODS: Pathology slides from
      patients who underwent CLM resection (irrespective of preoperative chemotherapy
      status) were rereviewed by a blinded pathologist. Pathologic response was
      recorded as the summation of percentage necrosis, fibrosis and acellular mucin.
      Associations between pathologic response, its components, preoperative
      chemotherapy, and survival were analyzed. RESULTS: Pathology slides were
      rereviewed in 366 patients undergoing CLM resection from 2003 to 2007.
      Preoperative chemotherapy was administered in 249 (68 %) patients, who, when
      compared to no preoperative chemotherapy patients, had higher rates of overall
      pathologic response (57 vs. 46 %, P < .01), fibrosis (21 vs. 12 %, P < .01) and
      acellular mucin (6 vs. 3 %, P = .05) but similar rates of necrosis (30 vs. 31 %,
      P = .30). In patients receiving preoperative chemotherapy, overall pathologic
      response >= 75 % (5 year, 83 vs. 47 %, P < .01) and fibrosis >= 40 % (5 year, 87
      vs. 51 %, P < .01) independently correlated with disease-specific survival after
      hepatectomy. Preoperative hepatic artery infusion chemotherapy (P = .04) and
      bevacizumab (P = .05) were marginally associated with overall pathologic response
      and fibrosis, respectively. CONCLUSIONS: Fibrosis is the predominant chemotherapy
      related pathologic alteration driving the association of treatment response with
      survival after CLM resection. Necrosis in CLM is not related to chemotherapy or
      outcome.

PMID- 22476754
TI  - Diffuse infiltrative hepatocellular carcinoma: assessment of presentation,
      treatment, and outcomes.
AB  - BACKGROUND: Data on infiltrating hepatocellular carcinoma (HCC) are limited. We
      sought to define treatment and outcome of patients treated with infiltrating HCC
      compared with patients who had advanced multifocal HCC. METHODS: Between January
      2000 and July 2011, a total of 147 patients with advanced HCC were identified
      from the Johns Hopkins Hospital database (infiltrative, n = 75; multifocal, n =
      72). Clinicopathologic data were compared by HCC subtype. RESULTS: Patients with
      infiltrating HCC had higher alfa-fetoprotein levels (median infiltrative, 326.5
      ng/mL vs. multifocal, 27.0 ng/mL) and larger tumors (median size, infiltrating,
      9.2 cm vs. multifocal, 5.5 cm) (P < 0.05). Imaging failed to reveal a discrete
      lesion in 42.7 % of patients with infiltrating HCC. Most infiltrating HCC lesions
      presented as hypointense on T1-weighted images (55.7 %) and hyperintense on T2
      weighted images (80.3 %). Among patients with infiltrating HCC, most (64.0 %)
      were treated with intra-arterial therapy (IAT), and periprocedural morality was
      2.7 %. Patients treated with IAT had longer survival versus patients receiving
      best support care (median survival, IAT, 12 months vs. best supportive care, 3
      months; P = 0.001). Survival after IAT was similar among patients treated with
      infiltrating HCC versus multifocal HCC (hazard ratio 1.29, 95 % confidence
      interval 0.82-2.03; P = 0.27). Among infiltrating HCC patients, pretreatment
      bilirubin >2 mg/dL and alfa-fetoprotein >400 ng/mL were associated with worse
      survival after IAT (P < 0.05). Patients with progressive disease after IAT had
      higher risk of death versus patients who had stable/responsive disease (hazard
      ratio 3.53, 95 % confidence interval 1.49-8.37; P = 0.004). CONCLUSIONS: Patients
      with infiltrative HCC often present without a discrete lesion on imaging. IAT for
      infiltrative HCC was safe and was associated with survival comparable to IAT
      outcomes for patients with multifocal HCC. Infiltrative HCC morphology is not a
      contraindication to IAT therapy in select patients.

PMID- 22476755
TI  - Use of magnetic resonance imaging in detection of breast cancer recurrence: a
      systematic review.
AB  - BACKGROUND: Diagnosis of breast cancer recurrence can be difficult as a result of
      the presence of scar tissue in the breast. Magnetic resonance imaging (MRI) may
      be superior to traditional imaging in diagnosis of recurrence because of its
      ability to differentiate malignancy from scarring. Current guidelines on
      investigation of suspected breast cancer recurrence recommend MRI when other
      investigations have equivocal findings. We performed the first systematic review
      on this topic. METHODS: Literature search revealed 35 potentially relevant
      studies; 10 were included in final analysis. Included were clinical studies
      comparing MRI with another diagnostic modality for diagnosis of breast cancer
      recurrence, with at least 10 patients, in the English language. Data extraction
      focused on sensitivity and specificity of standard diagnostic modalities and MRI
      for diagnosis of local disease recurrence. RESULTS: In total 494 patients were
      assessed across 10 studies; all were case series. Sensitivity of MRI for
      detection of recurrence ranged 75-100 %, while specificity ranged 66.6-100 %.
      Both sensitivity and specificity increased when MRI was performed after a longer
      time interval from the original surgery, although the longest follow-up reported
      was only 36 months. A negative MRI can avoid the need for further biopsy.
      CONCLUSIONS: Available data are based on clinically heterogeneous case series and
      superiority over standard triple assessment for breast cancer recurrence has not
      been proven. At present, MRI cannot be recommended in the routine diagnostic
      assessment for breast cancer recurrence but has a potentially useful role as a
      second-line investigation. A negative MRI is more useful than a positive MRI as
      positive MRIs require further investigation.

PMID- 22476756
TI  - Technical considerations in surgery for retroperitoneal sarcomas: position paper
      from E-Surge, a master class in sarcoma surgery, and EORTC-STBSG.
AB  - BACKGROUND: Surgery is the principal treatment for retroperitoneal sarcoma. These
      tumors typically involve or abut multiple organs and therefore require
      multivisceral resections. Despite the complexity of such operations, a
      standardized approach has not been described. As a result, referral centers often
      see patients who have undergone suboptimal surgery, with gross disease left
      behind. This is one of the causes of the dismal prognosis of this disease.
      METHODS: These consensus statements came out from E-Surge, an educational
      symposium with live sarcoma surgery, performed by European and North American
      expert sarcoma surgeons illustrating an optimal technique to an international
      audience, held in 2010 and 2011. The content was then shared among members of the
      local subcommittee of European Organization for Research and Treatment of Cancer
      (EORTC)-Soft Tissue and Bone Sarcoma Group (STBSG). RESULTS: An attempt to
      describe a reproducible and standardized approach to these tumors is illustrated.
      A detailed description of the different procedures according to the variety of
      different presentations is made. CONCLUSIONS: The approach described herein
      should be used as the reference standard in clinical practice and serve to
      perform quality check of local treatment in future trials.

PMID- 22476757
TI  - Evaluation of tumor stiffness by elastography is predictive for pathologic
      complete response to neoadjuvant chemotherapy in patients with breast cancer.
AB  - BACKGROUND: Breast elastography (EG), which can objectively evaluate tumor
      stiffness, has been useful for differentiation of benign and malignant breast
      lesions. However, the value of EG for prediction of response to systemic therapy
      is poorly understood. METHODS: The baseline evaluations of EG in 55 patients who
      received neoadjuvant chemotherapy were reviewed. We investigated the correlation
      between tumor stiffness and response to neoadjuvant chemotherapy. Tumor stiffness
      was evaluated by the Tsukuba elasticity scoring system. RESULTS: The mean EG
      scores were significant lower for the clinical and pathologic complete response
      (pCR) groups than for the others. When we categorized patients into two groups
      according to tumor stiffness, 26 patients were assigned to the low EG group
      (soft, scores from 1 to 3) and 29 patients were assigned to the high EG group
      (hard, score 4 and 5). The low EG group had significantly higher clinical
      complete response and pCR rates than the high EG group (clinical complete
      response, low EG group 38 % vs. high EG group 10 %, P = 0.024; pCR, low EG group
      50 % vs. high EG group 14 %, P = 0.003, respectively). Furthermore, multivariate
      analysis indicated that estrogen receptor, human epidermal growth factor receptor
      2, and low EG (odds ratio 13.04, 95 % confidence interval 1.19-458.28, P = 0.035)
      were independent predictive factors of pCR. CONCLUSIONS: Tumor stiffness
      evaluated by EG bears predictive potential for response to neoadjuvant
      chemotherapy. Stiffness evaluated by EG may be recognized as a clinically
      significant tumor characteristic, comparable to other data obtained by functional
      imaging techniques.

PMID- 22476758
TI  - Axillary lymph node status in unifocal, multifocal, and diffuse breast
      carcinomas: differences are related to macrometastatic disease.
AB  - BACKGROUND: Multifocality in breast carcinoma is associated with an increased
      propensity to metastasis. However, it is not clear whether this propensity
      manifests in the form of macrometastases or as presumably less-significant low
      volume metastatic disease. METHODS: A total of 948 cases of invasive breast
      carcinoma documented in large-format histology sections and assessed with
      detailed radiologic-pathologic correlation were categorized as unifocal,
      multifocal, or diffuse on the basis of the subgross distribution of the invasive
      component. Rates of macrometastases (>2 mm), micrometastases (0.2-2 mm), and
      isolated tumor cells (<0.2 mm) in these categories were compared. The influence
      of tumor size and histology grade on lymph node positivity rates was also tested.
      RESULTS: Macrometastases were present in 20.4% (112 of 550) of unifocal, 48.3%
      (172 of 356) of multifocal, and 61.9% (26 of 42) of diffuse cases (P < 0.0001).
      Among the macrometastatic cases, more than three nodes were involved in 18.9% (21
      of 112) of unifocal, 35.5% (61 of 172) of multifocal, and 50.0% (13 of 26) of
      diffuse cases. The rates of micrometastases (5.1, 5.1, and 2.4% unifocal,
      multifocal, and diffuse, respectively) and isolated tumor cells (4.5, 3.7, and
      2.4% unifocal, multifocal, and diffuse, respectively) were low and similar in all
      examined categories. The relative risk (RR) of having macrometastatic disease was
      approximately doubled (RR 2.3726, P < 0.0001) in multifocal and tripled (RR
      3.0562, P < 0.0001) in diffuse compared to unifocal cases. The findings were
      similar for all size categories, tumor grade categories, and sentinel lymph
      nodes, as well as all examined lymph nodes. CONCLUSIONS: The significantly
      increased lymph node positivity rates in multifocal and diffuse invasive breast
      carcinomas results from large-volume macrometastatic disease.

PMID- 22476759
TI  - Influence of exudates of the kelp Laminaria digitata on biofilm formation of
      associated and exogenous bacterial epiphytes.
AB  - Wild populations of brown marine algae (Phaeophyta) provide extensive surfaces to
      bacteria and epiphytic eukaryotes for colonization. On one hand, various
      strategies allow kelps prevent frond surface fouling which would retard growth by
      reducing photosynthesis and increasing pathogenesis. On the other hand,
      production and release of organic exudates of high energy value, sometimes in
      association with more or less selective control of settlement of epiphytic
      strains, allow bacteria to establish surface consortia not leading to
      macrofouling. Here, we present the analysis of adhesion and biofilm formation of
      bacterial isolates from the kelp Laminaria digitata and of characterized and
      referenced marine isolates. When they were grown in flow cell under standard
      nutrient regimes, all used bacteria, except one, were able to adhere on glass and
      then develop as biofilms, with different architecture. Then, we evaluated the
      effect of extracts from undisturbed young Laminaria thalli and from young thalli
      subjected to oxidative stress elicitation; this latter condition induced the
      production of defense molecules. We observed increasing or decreasing adhesion
      depending on the referenced strains, but no effects were observed against strains
      isolated from L. digitata. Such effects were less observed on biofilms. Our
      results suggested that L. digitata is able to modulate its bacterial
      colonization. Finally, mannitol, a regular surface active component of Laminaria
      exudates was tested individually, and it showed a pronounced increased on one
      biofilm strain. Results of these experiments are original and can be usefully
      linked to what we already know on the oxidative halogen metabolism peculiar to
      Laminaria. Hopefully, we will be able to understand more about the unique
      relationship that bacteria have been sharing with Laminaria for an estimated one
      billion years.

PMID- 22476760
TI  - Measurement of the signs of methyl 13C chemical shift differences between
      interconverting ground and excited protein states by R(1rho): an application to
      alphaB-crystallin.
AB  - Carr-Purcell-Meiboom-Gill relaxation dispersion (CPMG RD) NMR spectroscopy has
      emerged as a powerful tool for quantifying the kinetics and thermodynamics of
      millisecond time-scale exchange processes involving the interconversion between a
      visible ground state and one or more minor, sparsely populated invisible
      'excited' conformational states. Recently it has also become possible to
      determine atomic resolution structural models of excited states using a wide
      array of CPMG RD approaches. Analysis of CPMG RD datasets provides the magnitudes
      of the chemical shift differences between the ground and excited states, Deltapi,
      but not the sign. In order to obtain detailed structural insights from, for
      example, excited state chemical shifts and residual dipolar coupling
      measurements, these signs are required. Here we present an NMR experiment for
      obtaining signs of (13)C chemical shift differences of (13)CH(3) methyl groups
      using weak field off-resonance R(1rho) relaxation measurements. The accuracy of
      the method is established by using an exchanging system where the invisible,
      excited state can be converted to the visible, ground state by altering sample
      conditions so that the signs of Deltapi values obtained from the spin-lock
      approach can be validated against those measured directly. Further, the spin-lock
      experiments are compared with the established H(S/M)QC approach for measuring
      signs of chemical shift differences and the relative strengths of each method are
      discussed. In the case of the 650 kDa human alphaB-crystallin complex where there
      are large transverse relaxation differences between ground and excited state
      spins the R(1rho) method is shown to be superior to more 'traditional'
      experiments for sign determination.

PMID- 22476761
TI  - Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory
      or relapsed aggressive B-cell lymphoma.
AB  - This study was conducted to evaluate the efficacy and safety of Rituximab,
      Gemcitabine, Cisplatin, and Dexamethasone (R-GDP) in relapsed or refractory
      aggressive B-Cell Non-Hodgkin's Lymphoma (NHL). Treatments consisted of rituximab
      375 mg/m2, i.v. on day 1; gemcitabine 1,000 mg/m2, i.v. on days 1 and 8,
      dexamethasone 40 mg i.v. on days 1-4, and cisplatin 25 mg/m2 i.v. on days 1-3,
      every 21 days. The primary end-points were the overall survival (OS) and
      progression-free survival (PFS). Secondary endpoints included response rate (ORR;
      CR) and toxicities. Eligible patients could then proceed to high-dose
      chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or receive up
      to six treatment cycles. From January 2005 to December 2010, 50 successive
      patients at Tianjin cancer hospital lymphoma department were enrolled in this
      study. All patients were recurrent or refractory aggressive B-cell NHL, including
      diffuse large B-cell lymphoma (n=30) and follicular lymphoma grade 3b (n=20). The
      median follow-up time was 42 months (range, 12-70). After two cycles, the overall
      response rate was 72.0%, with a CR/CRu rate of 56%. The 2-year OS and PFS of all
      patients were 70.0 and 48.0%, respectively. Grade III-IV neutropenia and
      thrombocytopenia occurred in 34 and 40% of patients, respectively. Twenty-one
      patients (42%) proceeded to ASCT. Higher International Prognostic Index and
      refractory disease were independently associated with worse survival and
      progression-free survival. R-GDP chemotherapy in patients with refractory or
      relapsed aggressive B-Cell NHL was effective as a salvage therapy and helpful for
      HDC/ASCT.

PMID- 22476762
TI  - Cutaneous blastic plasmacytoid dendritic cell neoplasm occurring after
      spontaneous remission of acute myeloid leukemia: a case report and review of
      literature.
AB  - Spontaneous remission of acute myeloid leukemia (AML) is an extremely uncommon
      event. The etiology is associated with infection, blood transfusion or
      granulocyte colony-stimulating factor therapy, which trigger immune responses to
      exert an antileukemic effect. The remission is usually temporary and followed by
      rapid relapse. However, we present a case of a 42-year-old man with spontaneous
      remission of AML-M5a, who did not relapse but developed a rare and aggressive
      lymphoma, named cutaneous blastic plasmacytoid dendritic cell neoplasm (BPDCN).
      The neoplasm cells are positive for CD4, CD56, CD43, CD45, and CD123, but
      negative for other lineage-specific markers. To our knowledge, this is the first
      report of BPDCN occurring after spontaneous remission of AML, although it has
      been observed that some BPDCN could shift to myeloid leukemia. Occurrence of the
      two diseases is more than a coincidence. Discovery of such cases may shed further
      light on the inner connection between BPDCN and myeloid disorders.

PMID- 22476764
TI  - [The palliative care team in the intensive care unit].
AB  - The aim of palliative care is to relieve suffering and stabilize or improve
      quality of life. Prolongation of life and focus on quality of life seem to be at
      first glance mutually exclusive. However, in daily clinical routine they
      occasionally do simultaneously occur, when further medical treatment to prolong
      life is not successful, not appropriate, or simply refused by the patient. In
      general, basic competencies in palliative care should be offered by the intensive
      care unit teams. In complex cases, it can be reasonable to integrate a palliative
      care team (PCT) which can support treatment for those patients with regard to
      symptom-oriented therapy. They also facilitate referral of seriously ill patients
      to a hospice or home. Palliative care consultation is recommended, if distressing
      symptoms can not be alleviated sufficiently or support for referral of terminally
      ill patients is sought. In addition, a PCT can provide support in discussions
      about withdrawal of life-prolonging treatments and the aims of therapy.

PMID- 22476763
TI  - [Occurrence and prevention of errors in intensive care units].
AB  - Recognition and analysis of error constitutes an essential tool for quality
      improvement in intensive care units (ICUs). The potential for the occurrence of
      error is considerably high in ICUs. Although errors will never be completely
      preventable, it is necessary to reduce frequency and consequences of error. A
      system approach needs to consider human limitations and to design working
      conditions, workplace, and processes in ICUs in a way that promotes reduction of
      error. The development of a preventive safety culture must be seen as an
      essential task for ICUs.

PMID- 22476766
TI  - Overproduction of a potential red pigment by a specific self-immobilization
      biomembrane-surface liquid culture of Penicillium novae-zeelandiae.
AB  - A specific self-immobilization biomembrane-surface liquid culture (SIBSLC) was
      developed to overproduce a potential penicillium red pigment. Statistic analysis
      shows that both glucose concentration and membrane diameter are important factors
      influencing the yield of red pigment. After the optimization using central
      composite experimental design, the maximum yield of red pigment in shake flask
      reaches 4.25 g/l. The growth of strain HSD07B consists of three phases, and the
      pigment secreted in the decelerated phase, is originated from the interior of
      biomembrane where glucose exhaustion occurs. In addition, the batch and
      continuous SIBSLC were conducted for production of the pigment, and the latter
      was more competitive in consideration of the fact that it not only increased 61.5
      % of pigment productivity, but also simplified the production process. Moreover,
      the pigment produced by SIBSLC is potentially acceptable for food applications
      although it is distinguished from the co-cultured red pigment we reported
      previously in components.

PMID- 22476767
TI  - Direct fermentation of L (+)-lactic acid from cassava pulp by solid state culture
      of Rhizopus oryzae.
AB  - This study shows that Rhizopus oryzae is capable of directly utilizing cassava
      pulp alone to L-lactic acid in solid state fermentation (SSF). pH control at 6.0
      helped prevent end product inhibition. Increasing lactate titer was observed at
      the higher initial moistened water due to the higher degree of substrate swelling
      and hydrolysis. With shaking, limited ethanol production but no change in lactate
      titer was observed. Rigorous shaking gave better oxygen transfer but presumably
      caused cell damage leading to substrate utilization through the biosynthesis
      route. Supplementing cassava pulp with nitrogen enhanced growth but not lactate
      production. Under the optimal conditions, R. oryzae converted the sole cassava
      pulp into lactic acid at the titer of 206.20 mg per g initial dry pulp. With the
      help of commercial cellulase and glucoamylase, the dramatically increasing
      lactate titer of 463.18 mg per g initial dry pulp was achieved via SSF.

PMID- 22476768
TI  - Clinical correlations of miR-21 expression in colorectal cancer patients and
      effects of its inhibition on DLD1 colon cancer cells.
AB  - PURPOSE: MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly
      overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only
      a little is known about its functional role in CRC. METHODS: We examined the
      expression level of miR-21 in 44 paired samples of tumoral and non-tumoral colon
      tissues diagnosed for CRC using TaqMan real-time PCR method. Furthermore, we used
      miR-21 inhibitor (anti-miR-21) to transient knockdown of miR-21 in DLD-1 colon
      cancer cells and examined the effects of miR-21 silencing on viability,
      apoptosis, chemosensitivity, cell cycle, and migration of DLD1 cells. RESULTS:
      The expression levels of miR-21 were significantly increased in CRC tumor tissue
      (P < 0.0001). Significant differences in miR-21 levels were observed also between
      CRC tissues of patients with CRC in different clinical stages: I vs. II (P =
      0.033) and I vs. IV (P = 0.021). Kaplan-Meier analysis proved that the miR-21
      expression levels are correlated to shorter overall survival of CRC patients (P =
      0.0341). MiR-21 silencing in DLD1 cell line had no effect on the cell viability;
      however, when combined with chemotherapeutics (5-FU, L-OHP, and SN38), it
      contributed to the decrease of cell viability. Suppression of miR-21 decreased
      cell migration ability of DLD-1 cells by nearly 30 % (P = 0.016). CONCLUSION: We
      have confirmed the overexpression of miR-21 in CRC samples and its correlation
      with advanced disease and shorter overall survival. These findings could be
      described in part by the fact that CRC cells with increased expression of miR-21
      have higher migration ability.

PMID- 22476769
TI  - Initial responses of different health care professionals to various patients with
      headache: which are perceived as difficult?
AB  - BACKGROUND: Somatizing patients are considered a challenge to health care
      professionals. PURPOSE: The purpose of this study was to investigate the
      responses of different health care professionals' to patients with headache with
      different presentations. METHOD: Medical professionals (n = 77), clinical
      psychologists (n = 40), and psychology students (n = 115) were shown with four
      different manifestations of headache (neutral, somatic trauma, anxious-depressed,
      and severe somatizing). Health professionals rated their initial cognitive and
      emotional responses using a standardized questionnaire. RESULTS: The severe
      somatizing and anxious-depressed patients with headache evoked significantly more
      negative cognitive and emotional responses in all three samples. Even brief
      exposure to a patient's story yields specific initial responses from various
      health care professionals irrespective of their disciplines. CONCLUSION: Patients
      with headache and with a distressed presentation evoke significantly more
      negative cognitive and emotional responses in different health care
      professionals. Health care professionals should be more aware of their own
      response to difficult patients; in this way they will be more capable of managing
      this patient group.

PMID- 22476770
TI  - Persistence of critical flicker fusion frequency impairment after a 33 mfw SCUBA
      dive: evidence of prolonged nitrogen narcosis?
AB  - One of the possible risks incurred while diving is inert gas narcosis (IGN), yet
      its mechanism of action remains a matter of controversy. Although providing
      insights in the basic mechanisms of IGN, research has been primarily limited to
      animal studies. A human study, in real diving conditions, was needed. Twenty
      volunteers within strict biometrical criteria (male, age 30-40 years, BMI 20-23,
      non smoker) were selected. They performed a no-decompression dive to a depth of
      33 mfw for 20 min and were assessed by the means of critical flicker fusion
      frequency (CFFF) measurement before the dive, during the dive upon arriving at
      the bottom, 5 min before the ascent, and 30 min after surfacing. After this late
      measurement, divers breathed oxygen for 15 min and were assessed a final time.
      Compared to the pre-dive value the mean value of each measurement was
      significantly different (p < 0.001). An increase of CFFF to 104 +/- 5.1 % upon
      arriving to the bottom is followed by a decrease to 93.5 +/- 4.3 %. This
      impairment of CFFF persisted 30 min after surfacing, still decreased to 96.3 +/-
      8.2 % compared to pre-dive CFFF. Post-dive measures made after 15 min of oxygen
      were not different from control (without nitrogen supersaturation), 124.4 +/-
      10.8 versus 124.2 +/- 3.9 %. This simple study suggests that IGN (at least
      partially) depends on gas-protein interactions and that the cerebral impairment
      persists for at least 30 min after surfacing. This could be an important
      consideration in situations where precise and accurate judgment or actions are
      essential.

PMID- 22476771
TI  - Or47b receptor neurons mediate sociosexual interactions in the fruit fly
      Drosophila melanogaster.
AB  - In the fruit fly Drosophila melanogaster, social interactions especially among
      heterosexual couples have been shown to have significant impact on the circadian
      timing system. Olfaction plays a major role in such interactions; however, we do
      not know yet specifically which receptor(s) are involved. Further, the role of
      circadian clock neurons in the rhythmic regulation of such sociosexual
      interactions (SSIs) is not fully understood. Here, we report the results of our
      study in which we assayed the locomotor activity and sleep-wake behaviors of male
      male (MM), female-female (FF), and male-female (MF) couples from several wild
      type and mutant strains of Drosophila with an aim to identify specific olfactory
      receptor(s) and circadian clock neurons involved in the rhythmic regulation of
      SSI. The results indicate that Or47b receptor neurons are necessary for SSI, as
      ablation or silencing of these neurons has a severe impact on SSI. Further, the
      neuropeptide pigment dispersing factor (PDF) and PDF-positive ventral lateral
      (LN(v)) clock neurons appear to be dispensable for the regulation of SSI;
      however, dorsal neurons may be involved.

PMID- 22476772
TI  - Phase-shifting the fruit fly clock without cryptochrome.
AB  - The blue light photopigment cryptochrome (CRY) is thought to be the main
      circadian photoreceptor of Drosophila melanogaster. Nevertheless, entrainment to
      light-dark cycles is possible without functional CRY. Here, we monitored phase
      response curves of cry(01) mutants and control flies to 1-hour 1000-lux light
      pulses. We found that cry(01) mutants phase-shift their activity rhythm in the
      subjective early morning and late evening, although with reduced magnitude. This
      phase-shifting capability is sufficient for the slowed entrainment of the
      mutants, indicating that the eyes contribute to the clock's light sensitivity
      around dawn and dusk. With longer light pulses (3 hours and 6 hours), wild-type
      flies show greatly enhanced magnitude of phase shift, but CRY-less flies seem
      impaired in the ability to integrate duration of the light pulse in a wild-type
      manner: Only 6-hour light pulses at circadian time 21 significantly increased the
      magnitude of phase advances in cry(01) mutants. At circadian time 15, the mutants
      exhibited phase advances instead of the expected delays. These complex results
      are discussed.

PMID- 22476773
TI  - timeless is an essential component of the circadian clock in a primitive insect,
      the firebrat Thermobia domestica.
AB  - Recent studies show that the timeless (tim) gene is not an essential component of
      the circadian clock in some insects. In the present study, we have investigated
      whether the tim gene was originally involved in the insect clock or acquired as a
      clock component later during the course of evolution using an apterygote insect,
      Thermobia domestica. A cDNA of the clock gene tim (Td'tim) was cloned, and its
      structural analysis showed that Td'TIM includes 4 defined functional domains,
      that is, 2 regions for dimerization with PERIOD (PER-1, PER-2), nuclear
      localization signal (NLS), and cytoplasmic localization domain (CLD), like
      Drosophila TIM. Td'tim exhibited rhythmic expression in its mRNA levels with a
      peak during late day to early night in LD, and the rhythm persisted in DD. A
      single injection of double-stranded RNA (dsRNA) of Td'tim (dstim) into the
      abdomen of adult firebrats effectively knocked down mRNA levels of Td'tim and
      abolished its rhythmic expression. Most dsRNA-injected firebrats lost their
      circadian locomotor rhythm in DD up to 30 days after injection. DsRNA of cycle
      (cyc) and Clock genes also abolished the rhythmic expression of Td'tim mRNA by
      knocking down Td'tim mRNA to its basal level of intact firebrats, suggesting that
      the underlying molecular clock of firebrats resembles that of Drosophila.
      Interestingly, however, dstim also reduced cyc mRNA to its basal level of intact
      animals and eliminated its rhythmic expression, suggesting the involvement of
      Td'tim in the regulation of cyc expression. These results suggest that tim is an
      essential component of the circadian clock of the primitive insect T. domestica;
      thus, it might have been involved in the clock machinery from a very early stage
      of insect evolution, but its role might be different from that in Drosophila.

PMID- 22476774
TI  - Metamorphosis induces a light-dependent switch in Senegalese sole (Solea
      senegalensis) from diurnal to nocturnal behavior.
AB  - Light plays a key role in the development of biological rhythms in fish. Recent
      research in Senegal sole has revealed that spawning and hatching rhythms, larval
      development, and growth performance are strongly influenced by lighting
      conditions. However, the effect of light on the daily patterns of behavior
      remains unexplored. Therefore, the aim of this study was to investigate the
      impact of different photoperiod regimes and white, blue, and red light on the
      activity rhythms and foraging behavior of Solea senegalensis larvae up to 40 days
      posthatching (DPH). To this end, eggs were collected immediately after spawning
      during the night and exposed to continuous white light (LL), continuous darkness
      (DD), or light-dark (LD) 12L:12D cycles of white (LD(W)), blue (LD(B),
      lambda(peak) = 463 nm), or red light (LD(R), lambda(peak) = 685 nm). A filming
      scenario was designed to video record activity rhythms during day and night times
      using infrared lights. The results revealed that activity rhythms in LD(B) and
      LD(W) changed from diurnal to nocturnal on days 9 to 10 DPH, coinciding with the
      onset of metamorphosis. In LD(R), sole larvae remained nocturnal throughout the
      experimental period, while under LL and DD, larvae failed to show any rhythm. In
      addition, larvae exposed to LD(B) and LD(W) had the highest prey capture success
      rate (LD(B) = 82.6% +/- 2.0%; LD(W) = 75.1% +/- 1.3%) and attack rate (LD(B) =
      54.3% +/- 1.9%; LD(W) = 46.9% +/- 3.0%) during the light phase (ML) until 9 DPH.
      During metamorphosis, the attack and capture success rates in these light
      conditions were higher during the dark phase (MD), when they showed the same
      nocturnal behavioral pattern as under LD(R) conditions. These results revealed
      that the development of sole larvae is tightly controlled by light
      characteristics, underlining the importance of the natural underwater
      photoenvironment (LD cycles of blue wavelengths) for the normal onset of the
      rhythmic behavior of fish larvae during early ontogenesis.

PMID- 22476775
TI  - Circadian regulation of bird song, call, and locomotor behavior by pineal
      melatonin in the zebra finch.
AB  - As both a photoreceptor and pacemaker in the avian circadian clock system, the
      pineal gland is crucial for maintaining and synchronizing overt circadian rhythms
      in processes such as locomotor activity and body temperature through its
      circadian secretion of the pineal hormone melatonin. In addition to receptor
      presence in circadian and visual system structures, high-affinity melatonin
      binding and receptor mRNA are present in the song control system of male oscine
      passeriform birds. The present study explores the role of pineal melatonin in
      circadian organization of singing and calling behavior in comparison to locomotor
      activity under different lighting conditions. Similar to locomotor activity, both
      singing and calling behavior were regulated on a circadian basis by the central
      clock system through pineal melatonin, since these behaviors free-ran with a
      circadian period and since pinealectomy abolished them in constant environmental
      conditions. Further, rhythmic melatonin administration restored their
      rhythmicity. However, the rates by which these behaviors became arrhythmic and
      the rates of their entrainment to rhythmic melatonin administration differed
      among locomotor activity, singing and calling under constant dim light and
      constant bright light. Overall, the study demonstrates a role for pineal
      melatonin in regulating circadian oscillations of avian vocalizations in addition
      to locomotor activity. It is suggested that these behaviors might be controlled
      by separable circadian clockworks and that pineal melatonin entrains them all
      through a circadian clock.

PMID- 22476776
TI  - The mammalian circadian system is resistant to dioxin.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      that is bound and activated by many toxic ubiquitous environmental contaminants,
      including the halogenated aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). The AhR belongs to a family of proteins that contain basic helix
      loop-helix/Per-ARNT-SIM (bHLH/PAS) domains. The circadian clock protein, BMAL1,
      is also a bHLH-PAS transcription factor and has been shown to interact with the
      AhR. AhRs are expressed in nearly every mammalian tissue, including the
      suprachiasmatic nuclei (SCN), and previous studies have suggested that activation
      of the AhR with dioxins affects rhythmicity in circadian clocks. In this study,
      the authors tested the hypothesis that activation of the aryl hydrocarbon
      receptor with the potent dioxin, TCDD, alters the organization of the mammalian
      circadian system by measuring bioluminescence from tissues explanted from
      PER2::LUCIFERASE mice. They found that in vitro treatment of explanted tissues
      with TCDD did not alter the periods, amplitudes, or damping rates of the
      PER2::LUC rhythms compared with controls. Likewise, in vivo treatment with TCDD
      had no effect on the phase relationship between central and peripheral
      oscillators. Together, these data demonstrate that activation of the AhR with
      TCDD does not directly or systemically alter the mouse circadian system.

PMID- 22476777
TI  - Age affects photoentrainment in a nocturnal primate.
AB  - The endogenous circadian clock is entrained by external cues, mainly the light
      dark cycle received by photopigments located in the retina. The authors
      investigated (1) the effect of aging on the synchronization of the rest-activity
      rhythm and (2) the physiological basis of light photoreception in the gray mouse
      lemur, a nocturnal Malagasy primate. Old individuals were tested at different
      irradiance levels under 3 different light wavelengths previously shown to trigger
      maximal response in young adults. Investigators analyzed animal activity and
      temperature waveforms and used 2 reference treatments, strong white light and
      continuous darkness. The investigation revealed manifold effects of aging
      picturing a general loss of responsiveness to light and age-related changes in
      activity and temperature. In addition, the investigation shows that
      photoentrainment is a continuous process. Short wavelengths (430 nm) are more
      efficient than longer wavelengths (470-540 nm) at low light levels at dawn and
      across all light levels at dusk. This suggests an implication of S-cones,
      differential at dawn and dusk. This results, surprising for several reasons,
      calls for further investigation. The study brings an interesting contribution to
      the understanding of the physiological processes underlying synchronization to
      light.

PMID- 22476778
TI  - Sleep problems, chronotype, and diurnal preferences in children and adults with
      spina bifida.
AB  - Spina bifida meningomyelocele (SBM) is a neural tube defect that involves
      dysraphism of the spinal cord and extensive reorganization of the brain. The
      authors assessed the relationship between chronotype, diurnal preferences, and
      sleep problems in individuals with SBM and healthy controls. Although individuals
      with SBM showed the characteristic decelerating quadratic relationship between
      age and chronotype, the curve was displaced, peaking at a younger age in controls
      compared with SBM (23.4 vs. 29.2 years). Groups did not differ in morningness
      eveningness preferences. Individuals with SBM endorsed more sleep problems than
      controls. Further examination of the relationship between entrainment and sleep
      in SBM is warranted.

PMID- 22476779
TI  - Fibromyalgia syndrome and chronotype: late chronotypes are more affected.
AB  - Sleep has strong links to the symptomology of fibromyalgia syndrome (FMS), a
      diffuse musculoskeletal pain disorder. Information about the involvement of the
      circadian clock is, however, sparse. In this study, 1548 individuals with FMS
      completed an online survey containing questions on demographics, stimulant
      consumption, sleep quality, well-being and subjective pain, chronotype (assessed
      by the Munich ChronoType Questionnaire, MCTQ), and FMS impact. Chronotype
      (expressed as the mid-sleep-point on free days, corrected for sleep deficit on
      workdays, MSF(sc)) significantly correlated with stress-ratings, so-called
      "memory failures in everyday life," fatigue, FMS impact, and depression but not
      with anxiety. When chronotypes were categorized into 3 groups (early,
      intermediate, late), significant group differences were found for sum scores of
      perceived stress, memory failures in everyday life, fatigue, FMS impact, and
      depression but not anxiety, with late chronotypes being more affected than early
      chronotypes. Sleepiness ratings were highest in early chronotypes. Challenges of
      sleep quality and subjective pain were significantly increased in both early and
      late chronotypes. The results show that according to their reports, late
      chronotypes are more affected by fibromyalgia.

PMID- 22476781
TI  - Musculoskeletal ultrasonography assists the diagnostic performance of the 2010
      classification criteria for rheumatoid arthritis.
AB  - OBJECTIVE: We investigated whether musculoskeletal ultrasonography (MSKUS)
      assists the diagnostic performance of the 2010 rheumatoid arthritis (RA)
      classification criteria. METHODS: Sixty-nine early arthritis patients were
      consecutively enrolled. None of the patients had been treated. In MSKUS of
      bilateral wrist and finger joints from 22 sites, the findings obtained by gray
      scale and power Doppler (PD) assessment were graded on a semiquantitative scale
      from 0 to 3. Plain magnetic resonance imaging (MRI) of both wrist and finger
      joints was also examined. Diagnosis of RA was defined by the initiation of
      disease-modifying antirheumatic drugs within the first 3 months. The diagnostic
      performance of the patients was evaluated at entry using 2010 RA classification
      criteria in conjunction with MSKUS. RESULTS: The indispensable MSKUS finding for
      differentiating RA was the presence of a PD grade 2 or 3 that was superior to
      2010 RA classification criteria or MRI-proven bone edema. We propose that the
      decision tree algorithm of 2010 RA classification criteria with PD grade 2 or 3
      reveals the best discriminative ability. CONCLUSION: MSKUS, especially with a
      strong PD signal, is very useful to assist the diagnostic performance of the 2010
      RA classification criteria in the early recognition of RA.

PMID- 22476782
TI  - Solute-removal enhancement caused by local convective flow in a hemodialyzer.
AB  - Filtration, namely, convective mass transport through a hemodialysis membrane,
      has recently been utilized in maintenance hemodialysis to enhance the removal of
      high-molecular-weight uremic toxins. However, it has been practically impossible
      to estimate the clearance of solutes from hemodialyzers operated at predetermined
      net filtration rates, even if the mass-transfer parameters of the membrane are
      obtainable. Here, we discuss the effect of convective flow on the solute-removal
      performance of a hemodialyzer. The velocity and concentration profiles in the
      hemodialyzer were formulated on the basis of transport phenomena and obtained
      using the finite element method with commercially available software. The
      concentration profile obtained under conditions whereby local convective flow
      occurred through the membrane and the net filtration rate was negligible was
      measurably different from that obtained under conditions of no local convective
      flow. The result was a large discrepancy in the clearances obtained, indicating
      that local convective flow through a high-performance membrane cannot be ignored
      when estimating the solute-removal performance of a hemodialyzer containing such
      membranes or in designing the membrane and hemodialyzer--even if the hemodialyzer
      is operated at a net filtration rate of zero. The enhancement of clearance due to
      filtration, which had been discussed qualitatively elsewhere, was also quantified
      in relation to net filtration rate.

PMID- 22476783
TI  - Addition of a kidney to the normothermic ex vivo perfused porcine liver model
      does not increase cytokine response.
AB  - The addition of a kidney to the ex vivo liver perfused model may facilitate the
      circuit homeostatic balance of important biochemical parameters (i.e. pH changes,
      urea and creatinine, or glucose levels) but might also increase the inflammatory
      reaction produced. In this study, we compared the production of various cytokines
      between liver-kidney and liver-alone circuits. Seven livers were harvested from
      female pigs and perfused for 6 h. In five additional experiments, a kidney was
      also harvested and connected in parallel. Blood samples for interleukins (IL) 1,
      2, 4, 6, 8, 10, and 12, interferon (IFN)-gamma and tumor necrosis factor (TNF)
      alpha were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion.
      In the combined liver-kidney circuit, a significant increase was present only for
      IL-6 and IL-8, but this did not differ significantly from those recorded in the
      liver-alone circuit. All other cytokines were not modified from baseline levels.
      The addition of a kidney to the perfusion circuit does not stimulate a greater
      inflammatory reaction than that of the liver alone and therefore further confirms
      the safety of the experimental setups in view of more delicate experiments
      requiring strict homeostatic conditions.

PMID- 22476784
TI  - Label-free differentiation of human pituitary adenomas by FT-IR spectroscopic
      imaging.
AB  - Fourier transform infrared (FT-IR) spectroscopic imaging has been used to
      characterize different types of pituitary gland tumors and normal pituitary
      tissue. Freshly resected tumor tissue from surgery was prepared as thin
      cryosections and examined by FT-IR spectroscopic imaging. Tissue types were
      discriminated via k-means cluster analysis and a supervised classification
      algorithm based on linear discriminant analysis. Spectral classification allowed
      us to discriminate between tumor and non-tumor cells, as well as between tumor
      cells that produce human growth hormone (hGH+) and tumor cells that do not
      produce that hormone (hGH-). The spectral classification was compared and
      contrasted with a histological PAS and orange G stained image. It was further
      shown that hGH+ pituitary tumor cells show stronger amide bands than tumor cells
      that do not produce hGH. This study demonstrates that FT-IR spectroscopic imaging
      can not only potentially serve as a fast and objective approach for
      discriminating pituitary gland tumors from normal tissue, but that it can also
      detect hGH-producing tumor cells.

PMID- 22476785
TI  - Is nontarget screening of emerging contaminants by LC-HRMS successful? A plea for
      compound libraries and computer tools.
AB  - This review focuses on the possibilities and limits of nontarget screening of
      emerging contaminants, with emphasis on recent applications and developments in
      data evaluation and compound identification by liquid chromatography-high
      resolution mass spectrometry (HRMS). The general workflow includes determination
      of the elemental composition from accurate mass, a further search for the
      molecular formula in compound libraries or general chemical databases, and a
      ranking of the proposed structures using further information, e.g., from mass
      spectrometry (MS) fragmentation and retention times. The success of nontarget
      screening is in some way limited to the preselection of relevant compounds from a
      large data set. Recently developed approaches show that statistical analysis in
      combination with suspect and nontarget screening are useful methods to preselect
      relevant compounds. Currently, the unequivocal identification of unknowns still
      requires information from an authentic standard which has to be measured or is
      already available in user-defined MS/MS reference databases or libraries
      containing HRMS spectral information and retention times. In this context, we
      discuss the advantages and future needs of publicly available MS and MS/MS
      reference databases and libraries which have mostly been created for the
      metabolomic field. A big step forward has been achieved with computer-based tools
      when no MS library or MS database entry is found for a compound. The numerous
      search results from a large chemical database can be condensed to only a few by
      in silico fragmentation. This has been demonstrated for selected compounds and
      metabolites in recent publications. Still, only very few compounds have been
      identified or tentatively identified in environmental samples by nontarget
      screening. The availability of comprehensive MS libraries with a focus on
      environmental contaminants would tremendously improve the situation.

PMID- 22476786
TI  - Determination of perfluorinated alkyl acid concentrations in biological standard
      reference materials.
AB  - Standard reference materials (SRMs) are homogeneous, well-characterized materials
      used to validate measurements and improve the quality of analytical data. The
      National Institute of Standards and Technology (NIST) has a wide range of SRMs
      that have mass fraction values assigned for legacy pollutants. These SRMs can
      also serve as test materials for method development, method validation, and
      measurement for contaminants of emerging concern. Because inter-laboratory
      comparison studies have revealed substantial variability of measurements of
      perfluoroalkyl acids (PFAAs), future analytical measurements will benefit from
      determination of consensus values for PFAAs in SRMs to provide a means to
      demonstrate method-specific performance. To that end, NIST, in collaboration with
      other groups, has been measuring concentrations of PFAAs in a variety of SRMs.
      Here we report levels of PFAAs and perfluorooctane sulfonamide (PFOSA) determined
      in four biological SRMs: fish tissue (SRM 1946 Lake Superior Fish Tissue, SRM
      1947 Lake Michigan Fish Tissue), bovine liver (SRM 1577c), and mussel tissue (SRM
      2974a). We also report concentrations for three in-house quality-control
      materials: beluga whale liver, pygmy sperm whale liver, and white-sided dolphin
      liver. Measurements in SRMs show an array of PFAAs, with perfluorooctane
      sulfonate (PFOS) being the most frequently detected. Reference and information
      values are reported for PFAAs measured in these biological SRMs.

PMID- 22476787
TI  - Microwave-assisted headspace solid-phase microextraction to quantify polycyclic
      aromatic hydrocarbons in pine trees.
AB  - A methodology for the extraction and quantification of 16 polycyclic aromatic
      hydrocarbons (PAHs) based on microwave-assisted extraction coupled with headspace
      solid-phase microextraction followed by gas chromatography/mass spectroscopy was
      validated for needles and bark of two pine species (Pinus pinaster Ait. and Pinus
      pinea L.). The limits of detection were below 0.92 ng g(-1) (dry weight) for
      needles and below 0.43 ng g(-1) (dw) for bark. Recovery assays were performed
      with two sample masses spiked at three levels and the overall mean values were
      between 70 and 110 % for P. pinaster and 75 and 129 % for P. pinea. In the first
      species, the increase in sample mass lowered the recoveries slightly for most
      PAHs, whereas for the second, the recoveries were higher for the needles.
      Naturally contaminated samples from 4 sites were analysed, with higher levels for
      urban sites (1,320 and 942 ng g(-1) (dw) vs. 272 and 111 ng g(-1) (dw) for
      needles and 696 and 488 ng g(-1) (dw) vs. 270 and 103 ng g(-1) (dw) for bark)
      than for rural ones and also for P. pinaster samples over P. pinea. It is also
      shown that gas-phase PAHs are predominant in the needles (over 65 % of the total
      PAHs) and that the incidence for particulate material in bark, reaching 40 % as
      opposed to a maximum below 20 % for the needles. The method has proved to be fit
      and improved some of the existing approaches, on the assessment of particulate
      PAHs and bark levels.

PMID- 22476788
TI  - Risk factors for medically treated hypocalcemia after surgery for Graves'
      disease: a Swedish multicenter study of 1,157 patients.
AB  - BACKGROUND: For reasons that remain unclear, surgery for Graves' disease is
      associated with a higher risk of hypocalcemia than surgery for benign atoxic
      goiter. In the present study, we evaluated risk factors for postoperative
      hypocalcemia in patients undergoing operation for Graves' disease. METHODS: Data
      from 1,157 patients who underwent operation for Graves' disease between 2004 and
      2008 were extracted from the Scandinavian database for Thyroid and Parathyroid
      Surgery. Risk factors for postoperative hypocalcemia (in-hospital i. v. calcium;
      treatment with vitamin D analog at discharge, at 6 weeks, and at 6 months
      postoperatively) were evaluated by logistic regression analysis. RESULTS: Risk
      factors for i. v. calcium were low hospital volume of thyroid surgery (odds ratio
      [OR]: 95 % confidence interval [95 % CI], 0.99: 0.99-1.00), age (0.95: 0.91
      1.00), operative time (1.02: 1.01-1.02), university hospital (12.91: 2.68-62.30),
      and reoperation for bleeding (10.32: 1.51-70.69). The risk for treatment with
      vitamin D at discharge increased with operative time (1.01: 1.00-1.02), excised
      gland weight (1.01: 1.00-1.01), parathyroid autotransplantation (5.19: 2.28
      11.84), and reoperation for bleeding (12.00: 2.43-59.28). At 6 weeks, vitamin D
      medication was associated with gland weight (1.00: 1.00-1.01), and preoperative
      medication with beta-blockers (4.20: 1.67-10.55). At 6 months, vitamin D
      medication was associated with gland weight (1.00: 1.00-1.01) and reoperation for
      bleeding (10.59: 1.58-71.22). CONCLUSIONS: Risk factors for medically treated
      hypocalcemia varied at different times of follow-up. Young age, operative time,
      type of hospital, and parathyroid autotransplantation were associated with early
      postoperatively hypocalcemia. Preoperative beta-blocker treatment was a risk
      factor at the first follow-up. At early and late follow-up, gland weight and
      reoperation for bleeding were associated with medically treated hypocalcemia.

PMID- 22476789
TI  - Prevalence, serovars, phage types, and antibiotic susceptibilities of Salmonella
      strains isolated from animals in the United Arab Emirates from 1996 to 2009.
AB  - The aim of this study was to give some insights into the prevalence, serovars,
      phage types, and antibiotic resistances of Salmonella from animal origin in the
      United Arab Emirates. Data on diagnostic samples from animals (n = 20,871)
      examined for Salmonella between 1996 and 2009 were extracted from the databases
      of the Central Veterinary Research Laboratory in Dubai and from typed strains (n
      = 1052) from the Robert Koch Institute, Wernigerode Branch in Germany and
      analyzed for general and animal-specific trends. Salmonella was isolated from
      1,928 (9 %) of the 20,871 samples examined. Among the 1,052 typed strains, most
      were from camels (n = 232), falcons (n = 166), bustards (n = 101), antelopes (n =
      66), and horses (n = 63). The predominant serovars were Salmonella Typhimurium
      (25 %), Salmonella Kentucky (8 %), followed by Salmonella Frintrop (7 %), and
      Salmonella Hindmarsh (5 %). When analyzed by animal species, the most frequent
      serovars in camels were Salmonella Frintrop (28 %) and Salmonella Hindmarsh (21
      %), in falcons Salmonella Typhimurium (32 %), in bustards Salmonella Kentucky (19
      %), in antelopes Salmonella Typhimurium (9 %), and in horses Salmonella
      Typhimurium (17 %) and S. Kentucky (16 %). Resistance of all typed Salmonella
      strains (n = 1052) was most often seen to tetracycline (23 %), streptomycin (22
      %), nalidixic acid (18 %), and ampicillin (15 %). These data show trends in the
      epidemiology of Salmonella in different animal species which can be used as a
      base for future prevention, control, and therapy strategies.

PMID- 22476790
TI  - Prevalence, bacterial causes, and antimicrobial susceptibility profile of
      mastitis isolates from cows in large-scale dairy farms of Northern Ethiopia.
AB  - The study was undertaken to determine the prevalence of bovine mastitis, isolate
      mastitis causing bacteria, assess the association of some risk factors, and
      determine the antibiotic resistance pattern of bacterial isolates in cows in
      large-scale dairy farms of Northern Ethiopia. A total of 305 lactating and
      nonlactating cows were included in the present study. The overall prevalence of
      clinical and subclinical mastitis was 3.6 and 33.8 %, respectively. The quarter
      level prevalence was 15.4 %; from which, 11.9 and 1.1 % were subclinical form and
      blind teat, respectively, while the remaining 2.4 % were of clinical form.
      Staphylococcus aureus accounted for 36 % of the isolates followed by Escherichia
      coli (27.3 %). Risk factors including age (p < 0.001), parity (p < 0.001), and
      lactation stage (p = 0.02) showed significant association with the occurrence of
      mastitis. Higher prevalence was observed in both groups of older cows (i.e., 6-9
      years (odds ratio (OR) = 4.65, 95 % confidence interval (CI) = 2.74-7.89) and >9
      years (OR = 3.63, 95 % CI = 1.42-9.25)), cows with four to seven calves (OR =
      3.39, 95 % CI = 2.06-5.60), and cows in late lactation stage (OR = 3.79, 95 % CI
      = 1.64-8.75). In multivariable logistic regression analysis, age (p = 0.005) and
      lactation stage (p = 0.027) showed statistically significant association with the
      occurrence of mastitis. The antimicrobial susceptibility pattern showed high
      susceptibility of S. aureus to nalidixic acid (82.4 %) followed by
      chloramphenicol (58.8 %); however, these species were resistant to the rest of
      the antimicrobials tested. Highest resistance was observed against clindamycin
      and ampicillin. Coliform bacteria (E. coli and Klebsiella pneumoniae) showed
      resistance to most of the antimicrobials used. Detailed investigation is needed
      to identify the interplay of managemental and environmental risk factors to
      design appropriate control measures.

PMID- 22476791
TI  - Identification of virulence factors by multiplex PCR in Escherichia coli isolated
      from calves in Minas Gerais, Brazil.
AB  - In this study, multiplex PCR was employed to investigate the virulence factors of
      Escherichia coli strains isolated from 60-day-old calves. Faecal samples were
      collected from 54 calves at 12 dairy farms in the state of Minas Gerais, Brazil.
      A total of 156 isolates were obtained after culture and microbiological isolation
      and were tested by multiplex PCR for the presence of genes encoding toxins (Stx1,
      Stx2 and STa) and adherence factors (intimin, F41 and F5). Seventy of 156
      isolates were positive for at least one virulence factor: ten (14.3 %) from
      diarrhoeic animals and 60 (85.7 %) from healthy calves. The virulence markers
      identified were: Stx1 (82.8 %), eae (24.3 %), F41 (11.4 %), F5 (10 %), STa (4.28
      %) and Stx2 (4 %). In diarrhoeic animals, Stx1 (70 %) and F41 (30 %) were
      identified, while Stx1 (83.3 %), eae (28.3 %), F41 (8.3 %), F5 (11.6 %), STa (5
      %) and Stx2 (1.6 %) were detected in isolates from healthy calves. Mixed
      infections with pathotypes Shiga toxin-producing E. coli (STEC)/enteropathogenic
      E. coli, STEC/enterohaemorrhagic E. coli and STEC/other (eae/F5, Stx1/STa) were
      detected in five healthy calves. Pathogenic E. coli were identified in 59.26 % of
      all calves and on 75 % of the dairy farms studied, not only in diarrhoeic (five
      of six) but also in healthy calves (27 of 48), which demonstrates the importance
      of this agent in the aetiology of diarrhoea in calves in the state of Minas
      Gerais.

PMID- 22476792
TI  - Strategies of supplementation of female suckling calves and nutrition parameters
      of beef cows on tropical pasture.
AB  - The performance of female calves in creep feeding under different strategies of
      supplementation and milk production, intake, and digestibility of grazing Nellore
      and crossbred cows (Nellore * Holstein) during the dry-rainy transition season
      were assessed. Forty-four female beef suckling calves, with initial age between
      90 and 150 days and average initial body weight of 117.7 +/- 4.3 kg, and their
      respective dams (24 Nellore and 20 crossbred) with average initial body weight of
      417.5 +/- 8.3 kg, were used. The experimental treatments consisted of: control
      group--mineral mixture only; strategy 1--supplementation from 112 days prior to
      weaning (0.375 kg/animal/day); strategy 2--supplementation from 112 days prior to
      weaning, in increasing amounts of 0.15, 0.30, 0.45, and 0.60 kg/animal/day
      through the four experimental periods, respectively; and strategy 3-
      supplementation from 56 days prior to weaning (0.750 kg/animal/day). Calves from
      strategy 1 had greater (P < 0.05) average daily gain (0.672 kg/day) than control
      animals (0.582 kg/day) and greater (P < 0.05) efficiency of supplement use than
      the other groups. Crossbred cows produced more milk than Nellore cows (P < 0.05).
      Crossbred cows presented greater (P < 0.05) dry matter intake (DMI) than Nellore
      cows. However, no differences were found (P > 0.05) for nutrient digestibility
      among genetic types. It can be concluded that strategies of supplementation that
      present an equitable distribution of supplement provides greater weight gain in
      suckling female beef calves. Crossbred cows produce more milk and present greater
      DMI than Nellore cows. There are no differences in the nutrient digestibility
      between Nellore and Nellore * Holstein crossbred cows.

PMID- 22476793
TI  - Parent-reported prevalence of autism spectrum disorders in US-born children: an
      assessment of changes within birth cohorts from the 2003 to the 2007 National
      Survey of Children's Health.
AB  - The prevalence of autism spectrum disorders (ASD) from the 2007 National Survey
      of Children's Health (NSCH) was twice the 2003 NSCH estimate for autism. From
      each NSCH, we selected children born in the US from 1990 to 2000. We estimated
      autism prevalence within each 1-year birth cohort to hold genetic and non-genetic
      prenatal factors constant. Prevalence differences across surveys thus reflect
      survey measurement changes and/or external identification effects. In 2003,
      parents were asked whether their child was ever diagnosed with autism. In 2007,
      parents were asked whether their child was ever diagnosed with an ASD and whether
      s/he currently had an ASD. For the 1997-2000 birth cohorts (children aged 3-6
      years in 2003 and 7-10 years in 2007), relative increases between 2003 autism
      estimates and 2007 ASD estimates were 200-600 %. For the 1990-1996 birth cohorts
      (children aged 7-13 years in 2003) increases were lower; nonetheless, differences
      between 2003 estimates and 2007 "ever ASD" estimates were >100 % for 6 cohorts
      and differences between 2003 estimates and 2007 "current ASD" estimates were >80
      % for 3 cohorts. The magnitude of most birth cohort-specific differences suggests
      continuing diagnosis of children in the community played a sizable role in the
      2003-2007 ASD prevalence increase. While some increase was expected for 1997-2000
      cohorts, because some children have later diagnoses coinciding with school entry,
      increases were also observed for children ages >= 7 years in 2003. Given past ASD
      subtype studies, the 2003 "autism" question might have missed a modest amount (<=
      33 %) of ASDs other than autistic disorder.

PMID- 22476794
TI  - Value for the money spent? Exploring the relationship between expenditures,
      insurance adequacy, and access to care for publicly insured children.
AB  - This study examines the relationship between total state Medicaid spending per
      child and measures of insurance adequacy and access to care for publicly insured
      children. Using the 2007 National Survey of Children's Health, seven measures of
      insurance adequacy and health care access were examined for publicly insured
      children (n = 19,715). Aggregate state-level measures were constructed, adjusting
      for differences in demographic, health status, and household characteristics. Per
      member per month (PMPM) state Medicaid spending on children ages 0-17 was
      calculated from capitated, fee-for-service, and administrative expenses. Adjusted
      measures were compared with PMPM state Medicaid spending in scatter plots, and
      multilevel logistic regression models tested how well state-level expenditures
      predicted individual adequacy and access measures. Medicaid spending PMPM was a
      significant predictor of both insurance adequacy and receipt of mental health
      services. An increase of $50 PMPM was associated with a 6-7 % increase in the
      likelihood that insurance would always cover needed services and allow access to
      providers (p = 0.04) and a 19 % increase in the likelihood of receiving mental
      health services (p < 0.01). For the remaining four measures, PMPM was a
      consistent (though not statistically significant) positive predictor. States with
      higher total spending per child appear to assure better access to care for
      Medicaid children. The policies or incentives used by the few states that get the
      greatest value--lower-than-median spending and higher-than-median adequacy and
      access--should be examined for potential best practices that other states could
      adapt to improve value for their Medicaid spending.

PMID- 22476795
TI  - Facile size-tunable fabrication of functional tin dioxide nanostructures by
      multiple size reduction lithography.
AB  - A novel ultraviolet (UV)-assisted imprinting procedure that employs
      photosensitive tin(II) 2-ethylhexanoate is presented for the facile size-tunable
      fabrication of functional tin dioxide (SnO(2)) nanostructures by varying
      annealing temperatures. These imprinted SnO(2) nanostructures were also used as
      new masters for size reduction lithography. SnO(2) lines down to 40 nm wide were
      obtained from a silicon master with 200 nm wide lines by simply performing size
      reduction lithography twice. This leads to 80 and 87.5% reduction in the width
      and height of imprinted lines, respectively. An imprinted pattern annealed at 400
      degrees C demonstrated transmittance greater than 90% over the range of 350-700
      nm, which is high enough to make the pattern useful as a transparent SnO(2) mold.
      This demonstrated approach allows the accessibility to size-tunable molds,
      eliminating the need for conventional expensive imprinting masters with very fine
      structures, as well as functional SnO(2) nanostructures, potentially useful in
      applications where ordered surface nanostructures are required, such as photonic
      crystals, biological sensors, and model catalysts.

PMID- 22476796
TI  - Long-term follow-up results in 142 adult patients with moyamoya disease according
      to management modality.
AB  - BACKGROUND: To clarify the most beneficial treatment of the management modality
      based on our experience with adult moyamoya disease (MMD). METHODS: From 1998 to
      2010, clinical results of 142 patients (ischemic, 98; hemorrhagic, 44) with adult
      MMD were investigated according to management modality. Revascularization surgery
      (direct, indirect, and combined bypass) was performed in 124 patients. We
      observed the clinical course of 18 patients who were treated conservatively.
      Clinical outcome, angiographic features, hemodynamic change, and incidence of
      recurrent stroke were investigated pre- and postoperatively. RESULTS: In patients
      with ischemic MMD, direct and combined bypasses were more effective treatments to
      prevent recurrent ischemic stroke than indirect bypass surgery (P < 0.05). In
      patients with hemorrhagic MMD, rebleeding was less likely to occur in patients
      who had undergone bypass surgery. However, no significant difference was observed
      in the rebleeding rate between patients with and without revascularization
      surgery (P > 0.05). An angiogram after bypass surgery comparing the extent of
      revascularization and reduction of moyamoya vessels in patients treated with
      direct, indirect, and combined bypass showed a significant difference (P < 0.05)
      in favor of direct and combined bypass. Postoperative angiographic changes and
      SPECT results demonstrated significant statistical correlation (P < 0.05).
      CONCLUSION: Revascularization surgery was effective in further ischemic stroke
      prevention to a statistically significant extent. Direct and combined bypasses
      were more effective to prevent recurrent ischemic stroke than indirect bypass.
      However, there is still no clear evidence that revascularization surgery
      significantly prevents rebleeding in adult MMD patients. More significant
      angiographic changes were observed in direct and combined bypasses compared with
      indirect bypass.

PMID- 22476797
TI  - Who gets admitted? Study of referrals and admissions to an adolescent psychiatry
      inpatient facility over a 6-month period.
AB  - BACKGROUND: Child and adolescent psychiatry services have historically been
      neglected in Ireland, in terms of resource provision and research. AIM: To
      describe referral and admission patterns to an adolescent inpatient unit in
      Ireland. METHODS: We studied reasons for referral and admission decisions
      relating to all adolescents referred to St. Joseph's Adolescent Inpatient Unit
      (AIPU), Dublin in the first 6 months following its establishment in 2009.
      RESULTS: Forty-one adolescents were referred during the study period; 46 % were
      admitted. There was no difference between those admitted and not admitted in
      terms of gender (two-thirds were female), age (mean age 16.2 years), most common
      reason for referral (depression, in almost one-in-two) and suicidality (present
      in one-in-two). Amongst those referred, 46 % were resident in the primary
      catchment area. While a majority of admissions occurred within 5 days of referral
      (53 %), a significant minority were not admitted until over 20 days after
      referral (16 %). CONCLUSIONS: The demographic and clinical characteristics of
      adolescents referred and admitted to St. Joseph's AIPU are consistent with
      national and international patterns. At national level, the opening of additional
      beds for adolescents (such as St. Joseph's AIPU) has had positive effects on
      admission patterns; our findings indicate a need to further educate referrers
      about referral criteria, to optimise benefits derived from these new resources.
      Future studies could examine the potential roles of intensive support services in
      the community to further maximise use of scarce resources for this patient group.

PMID- 22476798
TI  - [Problems of urinary diversion].

PMID- 22476799
TI  - [Insufficiency of the efferent segment in continent cutaneous diversion].
AB  - Besides common requirements like universal applicability, reproducibility, and
      low complication rate, functionality and cosmetic aspects are essential in
      continent cutaneous diversions. Creation of the continence mechanism certainly
      represents the major surgical challenge in continent cutaneous diversions.
      Complete continence and ease of catheterization are mandatory for the patient's
      quality of life.High surgical competence, creativity, and variability are
      required in cases of revisional surgery for stomal insufficiency. In addition to
      accurate preoperative clinical, endoscopic, and radiologic evaluation, extensive
      expertise in the fields of continent urinary diversion and reconstructive urology
      allows performance of a surgical solution ideally adapted to the patient's
      individual situation. Between January 1990 and September 2011 we performed
      urinary diversion in 1,224 patients (mean follow-up 90.3 months). Continent
      urinary diversion was performed in 717 patients (59%); in 486 patients an
      ileocecal reservoir with continent cutaneous diversion, in 186 patients an
      ileocecal neobladder, and in 45 patients a sigma rectum pouch was created.
      Incontinence rate and stenosis rate in patients with appendico-umbilical stoma
      (n=219) were 2.3% and 10% and in patients with intussuscepted ileum nipple
      (n=267) nipple 5.2% and 2.7%. Stenosis usually can be corrected easily by simple
      excision of the obstructive scarred tissue or by stomal reconfiguration. Outlet
      failure may result from simple causes like fistula formation between reservoir
      and efferent segment or skin and nipple gliding or prolapse which can easily be
      repaired. More complex situations might require creation of a secondary
      continence mechanism. In our series of 486 patients having undergone continent
      cutaneous diversion in our department, 14 patients (appendico-umbilical stoma
      n=5, ileal nipple n=9) suffered from irreversible damage of the continent outlet.
      In 11 patients creation of a secondary intussuscepted ileal nipple and in 3
      patients a modified Managadze procedure was performed.In case of absence of the
      ileocecal valve (e.g. in primary ileal reservoirs, ileocolonic reservoirs without
      integrated ileocecal valve) and in case of a preexisting pouch of small capacity
      we prefer augmentation of the primary reservoirs with an ileocecal cup patch
      plasty in combination with the submucosally embedded appendix or intussuscepted
      ileal nipple serving as continent outlet. In our institution this was done in
      four patients who had undergone primary surgery elsewhere.

PMID- 22476800
TI  - [Management of urinary incontinence after orthotopic urinary diversion].
AB  - Orthotopic urinary diversion (OUD) is performed in almost half of all radical
      cystectomies. This review presents an overview of the incidence, pathophysiology,
      and management of urinary incontinence (UI) after OUD. Daytime and nighttime UI
      are reported in up to 15% and 45% of cases after OUD, respectively. UI after OUD
      is more frequent in women. Stress incontinence is the most common reason for
      daytime urinary leakage, while an absent vesicourethral reflex with reduced
      external sphincter muscle tone is associated with nighttime UI. Conservative
      management has limited therapeutic value in UI after OUD. Surgical approaches
      include adjustable and nonadjustable slings as well as the ProACT(r) system in
      mild stress UI. Implantation of the artificial urinary sphincter system AMS
      800(r) is the standard treatment for stress UI after OUD. Very limited data exist
      regarding results after implantation of newer artificial urinary sphincter
      systems such as the FlowSecure(r) and the Zephyr(r) ZSI 375 after OUD.

PMID- 22476802
TI  - [Androgen deprivation therapy in prostate cancer. Indication and systemic
      consequences].
AB  - Androgen deprivation therapy (ADT) is effective in prolonging the progression
      free survival of patients with symptomatic/metastatic prostate cancer (PC). The
      reduction of clinical symptoms of tumour disease and the reduction of tumour
      growth and metastatic dissemination is accompanied by systemic consequences of
      testosterone deficiency. These are hot flushes, fatigue due to reduction of
      muscular strength and muscle mass as well as anaemia. Moreover, patients develop
      cognitive impairment und depressive mood. Weight gain with insulin resistance,
      disturbances of lipid metabolism and gynecomastia are other effects of androgen
      deficiency. A decrease in bone mineral density may lead to an increased
      susceptibility to bone fractures. There are several options to reduce these side
      effects of ADT, e.g. physical activity, dietary supplementation, tailored
      pharmacological therapy and psychotherapy. The knowledge of these adjuvant
      treatment options, despite their palliative character, is relevant to optimize
      the quality of life of these patients.

PMID- 22476801
TI  - [Secondary malignancies in urinary diversions].
AB  - In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor
      risk in different forms of urinary diversion using isolated intestinal
      segments.In 44 German urological departments, operation frequencies, indications,
      patient age, and operation dates of the different forms of urinary diversion,
      operated between 1970 and 2007, could be registered. The secondary tumors up to
      2009 were registered as well and related to the numbers of the different forms of
      urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32
      secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and
      cystoplasty (13-fold) is significantly higher than in other continent forms of
      urinary diversion such as neobladders or pouches (p<0.0001). The difference
      between ureterosigmoidostomy and cystoplasty is not significant, nor is the
      difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%)
      (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is
      significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16
      tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly
      at the ureterocolonic borderline in contrast to only 50% following urinary
      diversions via isolated intestinal segments.From postoperative year 5 regular
      endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic
      (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy
      is necessary at least in the presence of symptoms or should be performed
      routinely at greater intervals. Following neobladders or conduits, only
      urethroscopies for urethral recurrence are necessary.

PMID- 22476803
TI  - [Reports from the DGU].

PMID- 22476804
TI  - [URO -- Telegram].

PMID- 22476805
TI  - [BDU-Journal occupational policy].

PMID- 22476807
TI  - A randomized, single-blind comparison of the efficacy and tolerability of
      hyaluronate acid and meloxicam in adult patients with Kashin-Beck disease of the
      knee.
AB  - The aim of this study was to prospectively evaluate the efficacy and tolerability
      of hyaluronic acid (HA) and meloxicam for the treatment of knee pain due to
      Kashin-Beck disease (KBD). A total of 162 patients with KBD-based knee pain were
      randomly assigned to treatment with a 3-week course of HA (n = 80) and a 12-week
      course of meloxicam (n = 82). Clinical assessments for each patient were made at
      0 (baseline), 1, 2, 4, 8, and 12 weeks. The primary efficacy measure was visual
      analog scale (VAS) pain score. Second efficacy measures comprised the Western
      Ontario and McMaster Universities (WOMAC) A (pain), B (stiffness), and C
      (function) scores as well as patients' and physicians' global assessments.
      Tolerability was evaluated based on adverse events (AEs) and physician reporting.
      The VAS rapidly decreased in both groups over 12 weeks. The VAS improvement
      observed in HA group was lower at week 1 (p = 0.001) but better at weeks 8 and 12
      (p < 0.001) than the meloxicam group, which were supported by the secondary
      variables of WOMAC A (p = 0.001) and WOMAC C (p < 0.001) scores and the global
      assessments of the patients and their physicians (p = 0.020 and 0.003,
      respectively). No serious AEs were reported, and the overall incidence of AEs
      among patients treated with meloxicam was higher than in patients treated with HA
      (p = 0.012). This study suggests that intra-articular injection of HA and
      administration of oral meloxicam should be efficacious and well tolerated in the
      treatment of knee pain due to KBD; the onset of action of meloxicam was faster
      than that of HA, whereas HA therapy resulted in a more prolonged increasing
      improvement of symptoms than meloxicam. In addition, HA treatment was likely
      superior to meloxicam with respect to tolerability. Other randomized double-blind
      studies are needed to confirm the findings of our open-label study.

PMID- 22476808
TI  - Comparison of the prognostic values of various inflammation based factors in
      patients with pancreatic cancer.
AB  - The aim of the present study was to determine whether C-reactive protein (CRP)
      based systemic inflammatory response scores (modified Glasgow prognostic score,
      mGPS; prognostic index, PI) have prognostic value superior to that of scores
      based on circulating white cells (neutrophil/lymphocyte ratio, NLR;
      platelet/lymphocyte ratio, PLR) or in combination with albumin (prognostic
      nutritional index, PNI) in patients with pancreatic cancer. The medical records
      of 177 patients with pancreatic adenocarcinoma were reviewed. Kaplan-Meier
      methodology and a multivariable Cox proportional hazards model were used to
      evaluate the potential prognostic factors. NLR > 5 was associated with higher
      white cell count, higher PLR, elevated CRP, hypoalbuminemia, increased mGPS, PI
      and PNI, poorer performance status (PS), greater weight loss and poorer tumor
      differentiation. On multivariate analysis, only NLR (HR, 2.537; 95 % CI, 1.313
      4.902; p = 0.006), PS, tumor-node-metastasis (TNM) staging, type of surgery and
      palliative chemotherapy were associated independently with survival, whereas PLR,
      mGPS, PI and PNI were not. NLR > 5 predicted poorer overall survival (OS)
      compared with NLR <= 5 (median OS, 4.133 and 9.300, respectively; p = 0.006). On
      the subgroup analysis, the median OS of patients with NLR > 5 was 5.767 months,
      whereas patients with NLR <= 5 who had received palliative chemotherapy had a
      median OS of 10.200 months (p < 0.001). Our study demonstrates that elevated NLR
      is superior to the mGPS, PI, PLR and PNI for prognostication in patients with
      pancreatic cancer.

PMID- 22476809
TI  - Docetaxel and cisplatin concurrent with radiotherapy versus 5-fluorouracil and
      cisplatin concurrent with radiotherapy in treatment for locally advanced
      oesophageal squamous cell carcinoma: a randomized clinical study.
AB  - This randomized clinical study was to assess and compare the efficacy and safety
      of two chemoradiotherapy (cisplatin + 5-fluorouracil + radiotherapy and cisplatin
      + docetaxel + radiotherapy) regimens in patients with unresectable local advanced
      oesophageal squamous cell carcinoma. Previously untreated patients with
      histologically or cytologically confirmed squamous cell carcinoma were randomly
      assigned into two groups (each had 45 patients): cisplatin + 5-fluorouracil +
      radiotherapy (PF) group and cisplatin + docetaxel + radiotherapy (DP) group. All
      patients received radiotherapy of 50.4 Gy (28 fractions of 1.8 Gy) over 5 weeks
      (5 fractions a week). Chemotherapy for PF group comprises 5-fluorouracil at days
      1-4 (250 mg/m(2)/day) and cisplatin (75 mg/m(2)) at day 1 of every 28-day cycle;
      full treatment course included 4 cycles. Chemotherapy for DP group comprises
      docetaxel (75 mg/m(2)) and cisplatin (75 mg/m(2)) at day 1 of every 28-day cycle;
      full treatment course included 4 cycles. Response, survival, progression and
      toxicity of both regimens were studied. Overall response rate (ORR) was 53.3 %
      for PF group and 73.3 % for DP group. Median overall survival (OS) time was 22.3
      months for PF group and 43.2 group months for DP: Patients of DP group had a
      significant longer overall median survival time (P < 0.05). Toxicity was
      acceptable; patients of PF group and patients of DP group did not showed
      significant difference in serious haematological event incidence (24.4 vs. 35.6
      %, P > 0.05). ORR and OS favour DP over PF in the treatment of patients with
      unresectable local advanced oesophageal squamous cell carcinoma.

PMID- 22476810
TI  - The effect of cryotherapy on oral mucosa: a study in healthy volunteers.
AB  - Oral cryotherapy causes local vasoconstriction, which reduces blood flow and
      reduces the cytotoxic damage to the oral mucosa, has been shown to reduce oral
      mucositis after intense cytostatic treatment. The main object of this study was
      to investigate the effect of oral cryotherapy on the temperature in the oral
      mucosa, the level of proinflammatory cytokine interleukin-6 (IL-6) in saliva and
      the effect on blood pressure in healthy volunteers, before and after 1 h of
      cooling the oral cavity with crushed ice. Twelve healthy volunteers [mean age
      32.4 (SD 13.2) (20-56) years] were treated with oral cryotherapy in the form of
      crushed ice. Temperature measurements were performed in the oral mucosa using
      infrared thermograph following a flowchart protocol. Blood pressure (BP) was
      measured with a sphygmomanometer. Saliva was analysed for inflammatory cytokine
      IL-6, using an enzyme-linked immunosorbent assay (ELISA). All participants
      fulfilled the cooling session. The temperature in the oral cavity decreased
      significantly (mean 12.9  degrees C, p < .002). The systolic BP was marginally
      but significantly higher after cooling (~5 mmHg, p = .019). We could not detect
      any differences in cytokine IL-6 levels before and after oral cooling. We
      conclude that cryotherapy during 1 h lowers the mucosal temperature as much as
      ~12.9  degrees C, which explains the significant protective effect against
      mucosal damage by cytostatic drugs. The cooling caused no increase in IL-6
      levels. Systemic blood pressure was marginally increased.

PMID- 22476811
TI  - The expression changes of Numblike in rat brain cortex after traumatic brain
      injury.
AB  - Numblike (Numbl) plays an important role in ependymal wall integrity and
      subventricular zone neuroblast survival. And Numbl is specifically expressed in
      the brain. However, its expression and function in the central nervous system
      lesion are still unclear. In this study, we performed a traumatic brain injury
      (TBI) model in adult rats and investigated the dynamic changes of Numbl
      expression in the brain cortex. Western blot and immunohistochemistry analysis
      revealed that Numbl was present in normal brain. It gradually decreased, reached
      the lowest point at day 3 after TBI, and then increased during the following
      days. Double immunofluorescence staining showed that Numbl immunoreactivity was
      found in neurons, but not astrocytes and microglia. Moreover, the 3rd day post
      injury was the apoptotic peak implied by the alteration of caspase-3. All these
      results suggested that Numbl may be involved in the pathophysiology of TBI and
      further research is needed to have a good understanding of its function and
      mechanism.

PMID- 22476812
TI  - The effectiveness of a motivational interviewing primary-care based intervention
      on physical activity and predictors of change in a disadvantaged community.
AB  - Little research exists on the impact of behavior change interventions in
      disadvantaged communities. We conducted a prospective study to explore the
      effectiveness of motivational interviewing on physical activity change within a
      deprived community and the social- psychological and motivational predictors of
      change in physical activity including stage of change, self-efficacy, social
      support, and variables from self-determination theory and the theory of planned
      behavior. Five motivational interviewing counsellors recruited 207 patients and
      offered motivational interviewing sessions to support physical activity behavior
      change. At 6-months there were significant improvements in physical activity,
      stage of change, and social support. A dose-response relationship was evident;
      those who attended 2 or more consultations increased their total physical
      activity, stage of change and family social support more than those who attended
      just one. Hierarchical regression analyses indicated that number of sessions and
      change in stage of change predicted 28.4% of the variance in change in total
      physical activity and, with social support from friends, 21.0% of the variance in
      change walking time. Change in perceived behavioral control and attitudes, friend
      social support, and number of sessions predicted 16.8% of the variance in change
      in vigorous physical activity. Motivational interviewing is an effective approach
      for promoting physical activity amongst lower socio-economic status groups in the
      short term. The study demonstrates good translational efficacy, and contributes
      to a limited number of physical activity interventions targeting low income
      groups in the UK.

PMID- 22476813
TI  - The patient-physician relationship in patients with chronic low back pain as a
      predictor of outcomes after rehabilitation.
AB  - For patients with chronic diseases, especially those with chronic low back pain,
      the patient-physician relationship is significant for treatment adherence. In a
      sample of N = 688 low back pain patients, we examined the hypothesis that aspects
      of the patient-physician relationship (e.g. satisfaction with care, trust in the
      physician, patient participation) have a significant association with outcomes
      (pain, disability, quality of life, pain-related psychological impairment) after
      a multimodal treatment program (rehabilitation) after adjusting for a number of
      sociodemographic, medical, and psychological factors. Results show that the
      patient-physician relationship is significantly associated with the outcome. In
      the medium term (6 months after rehabilitation), the effect of the patient
      physician relationship is clearer than in the short term (end of rehabilitation).
      In addition, risk factors for less improvement are female gender, higher age, low
      income, comorbidity, low treatment motivation, fear avoidance beliefs, and
      external locus of control. Future studies should examine the causal paths between
      the relationship variables and the outcome variables.

PMID- 22476815
TI  - Quality-score refinement of SSU rRNA gene pyrosequencing differs across gene
      region for environmental samples.
AB  - Due to potential sequencing errors in pyrosequencing data, species richness and
      diversity indices of microbial systems can be miscalculated. The "traditional"
      sequence refinement method is not sufficient to account for overestimations
      (e.g., length, primer errors, ambiguous nucleotides). Recent in silico and single
      organism studies have revealed the importance of sequence quality scores in the
      estimation of ecological indices; however, this is the first study to compare
      quality-score stringencies across four regions of the SSU rRNA gene sequence
      (V1V2, V3, V4, and V6) with actual environmental samples compared directly to
      corresponding clone libraries produced from the same primer sets. The nucleic
      acid sequences determined via pyrosequencing were subjected to varying quality
      score cutoffs that ranged from 25 to 32, and at each quality-score cutoff, either
      10 or 15 % of the nucleotides were allowed to be below the cutoff. When species
      richness estimates were compared for the tested samples, the cutoff values of
      Q27(15%), Q30(10%), and Q32(15%) for V1V2, V4, and V6, respectively, estimated
      similar values as obtained with clone libraries and Sanger sequencing. The most
      stringent Q tested (Q32(10%)) was not enough to account for species richness
      inflation of the V3 region pyrosequence data. Results indicated that quality
      score assessment greatly improved estimates of ecological indices for
      environmental samples (species richness and alpha-diversity) and that the effect
      of quality-score filtering was region-dependent.

PMID- 22476816
TI  - Clinicopathologic risk factors for the local recurrence of phyllodes tumors of
      the breast.
AB  - BACKGROUND: Phyllodes tumors (PTs) are rare breast tumors that usually occur in
      middle-aged women. Here we discuss our recent experiences in the diagnosis,
      surgical management, and clinical follow-up of this disease. METHODS: We
      retrospectively reviewed 164 patients with PTs who underwent surgical treatment
      at the Department of Surgery, Samsung Medical Center, Seoul, Korea, from January
      1995 to July 2009. Clinical and histopathological data were analyzed. RESULTS:
      The median follow-up period was 33.6 months (range 2-179 months), and the median
      patient age was 43 years (range of 11-72 years). Tumor size ranged from 1 to 30
      cm, with a median of 6.1 cm. A total of 148 patients (90.2 %) received local or
      wide excisions. Mastectomies were performed in 16 patients (9.8 %). The
      pathologic diagnoses included 82 benign (50.0 %), 42 borderline (25.6 %), and 40
      malignant PTs (24.4 %). The tumor border was infiltrating in 43 patients (26.2 %)
      and pushing in 116 patients (70.7 %). The resection margin was divided by based
      on the width. Local recurrence was observed in 31 patients (18.9 %), and distant
      metastasis developed in four patients with malignant PTs. Risk factors for the
      local recurrence of a PT were a positive resection margin (P = .029) and tumor
      size (P = .001). CONCLUSIONS: The presence of tumor cells on the resection margin
      was a strong prognostic factor for local recurrence of PTs. However, a 1 cm
      negative margin thickness did not confer any local control advantage over a
      thinner negative margin width.

PMID- 22476817
TI  - Short-term results and long-term oncologic outcomes between neoadjuvant
      chemoradiotherapy and adjuvant postoperative chemoradiotherapy for stage III
      rectal cancer: a case-matched study.
AB  - PURPOSE: To compare the short-term perioperative results and long-term oncologic
      outcomes between patients who underwent neoadjuvant chemoradiotherapy (NCRT) and
      patients who underwent postoperative adjuvant chemoradiotherapy (ACRT) for stage
      III rectal cancer. METHODS: From January 1997 to December 2008, a total of 47
      patients who were diagnosed as clinical stage III rectal cancer followed by NCRT
      were matched according to age, gender, and operation method to 47 patients with
      pathologic stage III rectal cancer who underwent ACRT. Clinical characteristics,
      surgical and pathologic outcomes, postoperative complications and recovery, and
      oncologic outcomes were compared between the two groups. RESULTS: There were no
      significant differences in demographics or preoperative characteristics between
      the NCRT and ACRT groups. Though more protective ileostomies were performed in
      the NCRT group, there was no statistical difference in operation times between
      the two groups. Patients in the NCRT group had a smaller tumor size (P < 0.001)
      and a smaller number of lymph nodes retrieved (P < 0.001). No differences were
      observed with respect to morbidity and recovery outcomes between the two groups.
      During the median 58-month follow-up periods, the NCRT group showed better
      disease-free survival and overall survival than the ACRT group (P = 0.002, P =
      0.001, respectively). CONCLUSIONS: NCRT in comparison to ACRT did not increase
      the risk of postoperative morbidity and provided better disease-free and overall
      survival in stage III rectal cancer patients.

PMID- 22476818
TI  - Clinicopathology and outcomes for mucinous and signet ring colorectal
      adenocarcinoma: analysis from the National Cancer Data Base.
AB  - PURPOSE: We evaluated clinical features and survival outcomes among patients with
      signet ring and mucinous histologies of colorectal adenocarcinoma by using data
      from the National Cancer Data Base (NCDB). METHODS: Patients aged 18-90 years
      with colorectal adenocarcinoma diagnosed between 1998 and 2002 were identified
      from the NCDB. Site-stratified (colon vs. rectum) survival analysis was performed
      by multivariate relative survival adjusted for multiple clinicopathologic and
      treatment variables. RESULTS: The study included 244,794 patients: 25,546 (10%)
      with mucinous, 2,260 (1%) with signet ring, and 216,988 (89%) with nonmucinous,
      non-signet ring adenocarcinoma. Mucinous and signet ring cancers were more
      frequently right-sided (60% and 62%, respectively) than were nonmucinous, non
      signet ring adenocarcinomas (42%, P < 0.001). Signet ring histology was
      associated with a higher stage (P < 0.001), and 77.2% of signet ring tumors were
      high-grade lesions, compared with 20% of mucinous and 17% of non-signet ring,
      nonmucinous adenocarcinomas (P < 0.001). After adjustment for covariates, signet
      ring histology was independently associated with higher risk of death [hazard
      ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51, and HR 1.57, CI 1.38
      1.77, for tumors located in the colon and rectum, respectively]. Mucinous tumors
      of the rectum (HR 1.22, CI 1.16-1.29), but not the colon (HR 1.03, CI 1.00-1.06),
      were associated with increased risk of death. CONCLUSIONS: Signet ring cell
      adenocarcinomas of the colon and rectum and mucinous adenocarcinomas of the
      rectum are associated with poorer survival. These aggressive histologic variants
      of colorectal adenocarcinoma should be targeted for research initiatives to
      improve outcomes.

PMID- 22476820
TI  - Publication and interpretation of clinical trial results: the need for caution.

PMID- 22476819
TI  - High expression of nuclear Snail, but not cytoplasmic staining, predicts poor
      survival in nasopharyngeal carcinoma.
AB  - BACKGROUND: Transcription factor Snail has been shown to promote tumor
      progression and metastasis in various cancers. However, its clinical significance
      in nasopharyngeal carcinoma (NPC) is still scanty. We have explored the clinical
      significance of Snail expression and its association with patient outcome in NPC.
      METHODS: Immunohistochemistry was used to examine the expression levels of Snail
      in 122 patients with NPC. RESULTS: Cytoplasmic Snail was detected in 37.7 %, and
      nuclear staining was detected in 49.2 % of primary tumors, respectively. No
      significant associations were found between cytoplasmic Snail and the
      clinicopathologic variables except lymph node metastasis (P = 0.042). However,
      nuclear Snail was significantly associated with tumor stage (P = 0.003), T
      classification (P = 0.045), lymph node metastasis (P = 0.019), distant metastasis
      (P = 0.003), and reduced E-cadherin expression (P = 0.021). Patients with high
      nuclear Snail expression, but not cytoplasmic staining, had significantly shorter
      survival than those with low expression (P < 0.001). Significantly, nuclear Snail
      was an independent prognostic predictor for NPC (P < 0.001). Furthermore, the
      prognostic impact was largely limited to stage III-IV patients. CONCLUSIONS: We
      demonstrated first that nuclear Snail, but not cytoplasmic staining, predicts
      worse outcome. In addition, the prognostic value in stage III-IV suggests that
      nuclear Snail could be a potential therapeutic target for late stage of NPC
      patients.

PMID- 22476821
TI  - Interventional options for severe aortic regurgitation after transcatheter aortic
      valve implantation: balloons, snares, valve-in-valve.

PMID- 22476822
TI  - An unusual finding after resuscitation: contusio cordis.

PMID- 22476823
TI  - Screening for obstructive sleep apnea in veterans with ischemic heart disease
      using a computer-based clinical decision-support system.
AB  - OBJECTIVES: To assess the validity of a handheld clinical decision-support system
      (CDSS) in detecting obstructive sleep apnea (OSA) in veterans with ischemic heart
      disease against polysomnography (PSG) and to compare the diagnostic accuracy of
      the CDSS versus the Berlin questionnaire. METHODS: We enrolled prospectively 143
      patients with underlying ischemic heart disease. Veterans with history of
      neurologic disease, systolic congestive heart failure, or receiving opiates were
      excluded from participation. Participants were asked to complete the Berlin
      Questionnaire and to answer all eight questions of CDSS-software. At the end of
      the interview, veterans were scheduled for an in-laboratory polysomnogram.
      RESULTS: Ninety one patients completed the study. The prevalence of OSA (AHI
      >=5/h) was 74.7 % with a median AHI of 11.5/h (range 0-90). When compared to PSG,
      the CDSS and the Berlin questionnaire achieved a sensitivity of 98.5 % [95 %
      confidence interval (CI) 92.1-100] and 80.9 % (95 % CI 69.5-89.4) and a
      specificity of 86.9 % (95 % CI 66.4-97.2) and 39.1 % (95 % CI 19.7-61.5) at a
      threshold value of AHI >=5 with a corresponding area under the curve of 0.93 (95
      % CI 0.85-0.97) and 0.60 (95 % CI 0.49-0.70); respectively. CONCLUSIONS: CDSS is
      a superior screening tool for identifying cardiac veterans with undiagnosed OSA
      than the BQ.

PMID- 22476824
TI  - Transumbilical single-port sleeve gastrectomy: initial experience and comparative
      study.
AB  - BACKGROUND: Sleeve gastrectomy is gaining relevance in the surgical armamentarium
      against obesity. The transumbilical single port has proved to be an attractive
      and safe alternative for a variety of minimally invasive abdominal surgeries. The
      purpose of this study is to evaluate the initial results of a group of patients
      operated by single-port sleeve gastrectomy compared with a group operated by
      conventional laparoscopic technique. PATIENTS AND METHODS: We present a
      prospective cohort study of two groups of consecutive patients with body mass
      index (BMI) between 35 and 55 kg/m(2), with an indication of sleeve gastrectomy.
      In 20 patients, we used a transumbilical single-port (TUSP) technique; in 22
      patients, we used the conventional laparoscopic (CL) technique. All surgeries
      were performed between June and December 2009 in the Gastrointestinal Surgery
      Department of Hospital Clinic, Barcelona. The same medical team, in a
      standardized fashion, carried out all surgeries. RESULTS: There were no
      differences between groups in body mass index (BMI), age, sex, number and type of
      comorbidities, or history of previous abdominal surgery. Operative time (79.2
      min) was significantly higher in the TUSP group (p = 0.002) than in the CL group
      (54.1 min). There were no conversions to open surgery in any of the patients
      operated upon via CL, but one conversion to laparoscopic surgery, requiring the
      addition of three trocars, in the TUSP group. There were no significant
      differences in morbidity or hospital stay between the groups. Percentage excess
      weight loss and excess BMI loss at 3 and 6 months, as indexes for improvement and
      resolution of comorbidities associated with obesity, showed that there were no
      significant differences between the groups. CONCLUSIONS: Transumbilical single
      port sleeve gastrectomy has proved to be safe, technically feasible, and
      reproducible, with results that are similar to those obtained with conventional
      laparoscopic surgery.

PMID- 22476825
TI  - Video: argon plasma coagulator in a 2-month-old child with tracheoesophageal
      fistula.
AB  - A 2 month-old boy was admitted to the authors' hospital because of regurgitation
      and persistent cough during breastfeeding. A chest X-ray examination and a barium
      esophagogram disclosed small amounts of barium passing in the trachea, suggesting
      a tracheoesophageal fistula (TEF). Bronchoscopy combined with upper
      gastrointestinal (GI) endoscopy performed with the patient under general
      anesthesia confirmed the fistula. The TEF was treated by injection of 1 ml
      Glubran 2 from the esophageal side. A nasogastric tube was placed for feedings,
      and 7 days later, a barium esophagogram showed a reduction of caliber but not
      complete closure of the TEF. Unsuccessful fistula obliteration with Glubran was
      attributed to technical difficulties in catheterization of the fistula orifice,
      mainly resulting from its close proximity to the upper esophageal sphincter and
      to its small caliber. Therefore, an argon plasma coagulator (APC) probe with a
      circumferentially oriented nozzle was used from the esophageal side as an
      alternative technique to fulgurate the residual fistula orifice (see video). A
      nasogastric tube was placed for feedings. Oral feeding was started 7 days later
      when a barium esophagogram confirmed complete fistula closure. At the 2-year
      follow-up visit, the boy was asymptomatic, and the barium esophagogram was
      negative. This report describes a case in which esophagoscopy gave a clear view
      of the fistula due to its direction from esophagus to trachea. Complete fistula
      obliteration was not obtained with Glubran. However, APC was successfully used to
      close the residual fistula orifice. The authors suggest that APC can be used as
      an alternative endoscopic technique to repair TEF when other techniques fail.

PMID- 22476827
TI  - Reply to: a letter to the editors: re: minimally invasive oesophagectomy: current
      status and future direction.

PMID- 22476826
TI  - A prospective study demonstrating the reliability and validity of two procedure
      specific evaluation tools to assess operative competence in laparoscopic
      colorectal surgery.
AB  - BACKGROUND: Laparoscopic colorectal surgery is considered an advanced minimally
      invasive procedure with a long, variable learning curve. Developing an evaluation
      tool is essential to ensure that individuals reach a certain level of competence
      prior to performing this procedure independently. To achieve standardization and
      wide implementation, an assessment tool must be reflective of practice across
      many institutions. STUDY DESIGN: The purpose of this study is to validate two
      procedure-specific evaluation tools for laparoscopic colorectal surgery that were
      developed using innovative consensus methodology. Two procedure-specific rating
      scales for laparoscopic right and sigmoid colectomy were created using the Delphi
      method. Nine novice and nine expert laparoscopic sigmoid colectomy videos were
      prospectively collected, and nine novice and ten expert laparoscopic right
      colectomy videos were recorded. The experts rated the videos using the procedure
      specific technical skills evaluation tool for either laparoscopic right colectomy
      or laparoscopic sigmoid colectomy. RESULTS: There were statistically significant
      differences between the expert and novice scores on the laparoscopic right
      colectomy evaluation tool: the median score of novices was 63.8% and the expert
      score was 73.1% (p = 0.02). Similarly, there was a significant difference between
      the median novice score on the sigmoid tool (58.6%) compared with the median
      expert score (70.7%) (p = 0.003). Cronbach's alpha was 0.82 for the right
      colectomy evaluation tool and 0.79 for the sigmoid rating scale. CONCLUSIONS: The
      procedure-specific evaluation tools for laparoscopic right and sigmoid colectomy
      demonstrate strong reliability and construct validity, and have the potential to
      be used for technical skills assessment and feedback.

PMID- 22476828
TI  - Tensile strength testing for resorbable mesh fixation systems in laparoscopic
      ventral hernia repair.
AB  - BACKGROUND: In an attempt to improve patient outcome and quality of life after
      laparoscopic ventral hernia repair, resorbable fixation devices have been
      developed to allow adequate mesh fixation while minimizing accompanying side
      effects as tack erosion and adhesion formation. MATERIALS AND METHODS: In
      experimental set-up, 24 pigs were treated by laparoscopic mesh placement. Two
      different meshes (PP/ORC and PP/ePTFE) and four fixation devices were evaluated:
      a 6.4 mm poly(D,L: )-lactide pushpin (tack I), a 6.8 mm poly(D,L: )-lactide with
      blunt tip (tack II), a 4.1 mm poly(glycolide-co-L-lactide) (tack III) and one
      titanium tack (control tack). A first group of animals (n = 12) was euthanized
      after 2 weeks survival and a second group (n = 12) after 6 months. At euthanasia,
      a relaparoscopy was performed to assess adhesion formation followed by laparotomy
      with excision of the entire abdominal wall. Tensile strength of the individual
      fixation systems was tested with the use of a tensiometer by measuring the force
      to pull the tack out of the mesh. Additionally, the foreign body reaction to the
      fixation systems was evaluated histologically as was their potential degradation.
      RESULTS: At 2 weeks the tensile strength was significantly higher for the control
      tack (31.98 N/cm2) compared to the resorbable devices. Except for tack II, the
      tensile strength was higher when the devices were fixed in a PP/ePTFE mesh
      compared to the PP/ORC mesh. After 6 months only tack III was completely
      resorbed, while tack I (9.292 N/cm2) had the lowest tensile strength. At this
      time-point similar tensile strength was observed for both tack II (29.56 N/cm2)
      and the control tack (27.77 N/cm2). Adhesions seem to be more depending on the
      type of mesh, in favor of PP/ePTFE. CONCLUSION: At long term, the 4.1 mm
      poly(glycolide-co-L-lactide) tack was the only tack completely resorbed while the
      6.8 mm poly(D,L: )-lactide tack with blunt tip reached equal strengths to the
      permanent tack.

PMID- 22476829
TI  - SLEEVEPASS: a randomized prospective multicenter study comparing laparoscopic
      sleeve gastrectomy and gastric bypass in the treatment of morbid obesity:
      preliminary results.
AB  - BACKGROUND: The long-term efficacy of laparoscopic Roux-en-Y gastric bypass
      (RYGB) in the treatment of morbid obesity has been demonstrated. Laparoscopic
      sleeve gastrectomy (SG) as a single procedure has shown promising short-term
      results, but the long-term efficacy of SG has not yet been demonstrated. The aim
      of this study was to determine the preliminary 30-day morbidity and mortality of
      RYGB and SG in a prospective multicenter randomized setting. METHODS: A total of
      240 morbidly obese (BMI = 35-66 kg/m2) patients evaluated by a multidisciplinary
      team were randomized to undergo either RYGB or SG. There were 117 patients in the
      RYGB group and 121 in the SG group; two patients had to be excluded after
      randomization. Both study groups were comparable regarding age, gender, BMI, and
      comorbidities. RESULTS: There was no 30-day mortality. The median operating time
      was significantly shorter in the SG group (66 min vs. 94 min, p < 0.001). All
      complications were recorded thoroughly. There were 7 (5.8 %) major complications
      following SG and 11 (9.4 %) after RYGB (p = 0.292). Nine (7.4 %) SG patients and
      20 (17.1 %) RYGB patients had minor complications (p = 0.023). The overall
      morbidity was 13.2 % after SG and 26.5 % after RYGB (p = 0.010). There were three
      (2.5 %) early reoperations after SG and four (3.3 %) after RYGB (p = 0.719).
      CONCLUSIONS: At 30-day analysis SG is associated with a shorter operating time
      and fewer early minor complications compared to RYGB. There were no significant
      differences in major complications or early reoperations. Long-term follow-up is
      required to determine the effect on weight loss, resolution of obesity-related
      comorbidities, and improvement of quality of life.

PMID- 22476830
TI  - Totally stapled gastrojejunal anastomosis using hybrid NOTES: single 12-mm trocar
      approach in a porcine model.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility of a totally
      stapled gastrojejunal anastomosis performed using one transabdominal 12-mm trocar
      and a gastroscope in a porcine model. METHODS: The procedure was carried out on
      six domestic pigs weighing 45 kg using a hybrid technique with a gastroscope and
      a 12-mm Hasson trocar, positioned in the left hypochondrium. At the end of the
      procedure a mechanical circular 21-mm gastrojejunal anastomosis was performed by
      inserting the stapler through a small gastrotomy after enlarging the trocar
      incision. RESULTS: In all six cases the procedure was completed through a single
      3 cm abdominal incision and without complications. The mean operating time was 2
      h, and endoscopic investigation showed that the anastomoses were intact, patent,
      and airtight. CONCLUSIONS: Totally stapled gastrojejunal anastomosis using a
      hybrid NOTES-single 12-mm trocar approach is a feasible procedure in the porcine
      model. Further survival studies are warranted, particularly to evaluate the
      functional results of this procedure.

PMID- 22476831
TI  - Cholecystectomy using a novel Single-Site((r)) robotic platform: early experience
      from 45 consecutive cases.
AB  - BACKGROUND: The aim of this work was to study the feasibility, safety, and
      efficacy of single-incision robotic cholecystectomy using a novel platform from
      Intuitive Surgical. METHODS: All operations were performed by the same surgeon.
      Parameters assessed included patient history, indication for surgery, operation
      time, complication rate, conversion rate, robot-related issues, length of
      hospital stay, postoperative pain, and time to return to work. All patients were
      followed for a 2-month period postoperatively. RESULTS: Forty-five patients (22
      women, 23 men) underwent single-incision robotic cholecystectomy from March 1 to
      July 15, 2011. There were no conversions to either conventional laparoscopy or
      laparotomy, although in three cases a second trocar was used. There were no major
      complications apart from a single case of postoperative hemorrhage. Average
      patient age was 47 +/- 12 years (range = 27-80 years) and average BMI was 30
      kg/m(2) (mean = 28.8 +/- 4 kg/m(2), range = 18.4-46.7 kg/m(2)). The primary
      indication for surgery was gallstones. The mean operation time (skin-to-skin) was
      84.5 +/- 25.5 min (range = 51-175 min), docking time was 5.8 +/- 1.5 min (range =
      4-11 min), and console time (net surgical time) was 43 +/- 21.9 min (range = 21
      121 min). Intraoperative blood loss was negligible. There were no collisions
      between the robotic arms and no other robot-related problems. Average
      postoperative length of stay was less than 24 h. The mean Visual Analog Pain
      Scale Score 6 h after the operation was 2.2 +/- 1.51 (range = 0-6) and patients
      returned to normal activities in 4.48 +/- 2.3 days (range = 1-9 days).
      CONCLUSIONS: Single-Site((r)) is a new platform offering a potentially more
      stable and reliable environment to perform single-port cholecystectomy. Both
      simple and complicated cholecystectomies can be performed with safety. The
      technique is possible in patients with a high BMI. The induction of
      pneumoperitoneum using the new port and the docking process require additional
      training.

PMID- 22476833
TI  - Reply to: doi:10.1007/s00464-010-1485-0: evaluation of factors affecting the
      difficulty of laparoscopic anterior resection for rectal cancer: "narrow pelvis"
      is not a contradiction.

PMID- 22476832
TI  - A head-to-head comparison between virtual reality and physical reality simulation
      training for basic skills acquisition.
AB  - BACKGROUND: This study aimed to investigate whether basic laparoscopic skills
      acquired with a virtual reality simulator (LapVRTM) are transferable to a
      standard video trainer (VT) and vice versa. METHODS: Three basic tasks were
      considered: peg transfer, cutting, and knot-tying. The physical models were
      custom-built as identical copies of the virtual models. Forty-four novices were
      randomized into two equal groups to be trained on the LapVRTM or the VT. Each
      task was practiced separately 12 times. Transferability of skills from one
      modality to the other was assessed by performing the same task on the alternative
      modality before and after training (crossover assessment). Performance metrics
      included path length, time, and penalty score. RESULTS: Both groups demonstrated
      significant performance curves for all tasks and metrics (p < 0.05). Plateaus
      were statistically equivalent between the groups for each task in terms of path
      length and time, and across all tasks in terms of the penalty score (p < 0.05).
      When each group was tested on the alternative modality there was a significant
      improvement for all tasks and metrics (p < 0.05). Comparing the plateau
      performance of one group with the performance achieved on the same simulator by
      the other group we found (a) no statistical deference in the penalty score (p <
      0.05), (b) a statistical difference in time and path length for cutting and knot
      tying (p < 0.05), and (c) an equal time performance for peg transfer (p < 0.05)
      but not for path length (p < 0.05). CONCLUSIONS: Both modalities provided
      significant enhancement of the novices' performance. The skills learned on the
      LapVRTM are transferable to the VT and vice versa. However, training with one
      modality does not necessarily mean a performance equivalent to that achieved with
      the other modality.

PMID- 22476834
TI  - Urogenital function following laparoscopic and open rectal cancer resection: a
      comparative study.
AB  - BACKGROUND: Sexual and urinary dysfunction is an established risk after pelvic
      surgery. Studies examining sexual and urinary function following laparoscopic and
      open rectal surgery give conflicting evidence for outcomes. The purpose of this
      study was to analyse the impact of the surgical technique on functional outcomes
      following laparoscopic or open resection for rectal cancer patients in a high
      volume laparoscopic unit. METHODS: All patients who underwent elective
      laparoscopic or open surgery for rectal cancer between September 2006 and
      September 2009 were identified from a prospectively collated database. Validated
      standardized postal questionnaires were sent to surviving patients to assess
      their postoperative sexual and urinary function. The functional data were then
      quantified using previously validated indices of function. RESULTS: A total of
      173 patients were identified from the database, of whom 144 (83 %) responded to
      the questionnaire-based study. Seventy-eight respondents had undergone
      laparoscopic rectal resection (49 men and 29 women), and 65 had an open procedure
      (41 men and 24 women). Both open surgery and laparoscopic surgery were associated
      with deterioration in urinary and sexual function. With regard to urinary
      function, there was no difference in the deterioration in open and laparoscopic
      groups in either gender. With regard to sexual function, in males one component
      of sexual function, namely, the incidence of successful penetration, showed less
      deterioration in the laparoscopic group (p = 0.04). However, in females,
      laparoscopic surgery was associated with significantly better outcomes in all
      aspects of sexual activity, specifically sexual arousal (p = 0.005), lubrication
      (p = 0.001), orgasm (p = 0.04), and the incidence of dyspareunia (p = 0.02).
      CONCLUSION: Laparoscopic total mesorectal excision for rectal cancer is
      associated with significantly less deterioration in sexual function compared with
      open surgery. This effect is particularly pronounced in women.

PMID- 22476835
TI  - The cost of surgical training: analysis of operative time for laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Duration of surgery is a main cost factor of surgical training. The
      purpose of this analysis of operative times for laparoscopic cholecystectomies
      (LC) was to quantify the extra time and related costs in regards to the surgeons'
      experience in the operating room (OR). METHODS: All LC performed between January
      01, 2005 and December 31, 2008 in 46 hospitals reporting to the database of the
      Swiss Association for Quality Management in Surgery (AQC) were analyzed (n =
      10,010). Four levels of seniority were specified: resident (R), junior consultant
      (JC), senior consultant (SC), and attending surgeon (AS). The differences in
      operative time according to seniority were investigated in a multivariable log
      linear and median regression analysis controlling for possible confounders. The
      OR costs were calculated by using a full cost rate in a teaching hospital.
      RESULTS: A total of 9,208 LC were available for analysis; 802 had to be excluded
      due to missing data (n = 212) or secondary major operations (n = 590). Twenty
      eight percent of the LC were performed by R as teaching operations (n = 2,591).
      Compared with R, the multivariable analysis of operative time showed a median
      difference of -2.5 min (-9.0; 4.8) for JC and -18 min (-25; -11) for SC and -28
      min (-35; -10) for AS, respectively. The OR minute costs were <euro>17.57,
      resulting in incremental costs of <euro>492 (159; 615) per operation in case of
      tutorial assistance. CONCLUSIONS: The proportion of LC performed as tutorial
      assistance for R remains low. Surgical training in the OR causes relevant case
      related extra time and therefore costs.

PMID- 22476836
TI  - The virtual reality simulator dV-Trainer((r)) is a valid assessment tool for
      robotic surgical skills.
AB  - BACKGROUND: Exponential development of minimally invasive techniques, such as
      robotic-assisted devices, raises the question of how to assess robotic surgery
      skills. Early development of virtual simulators has provided efficient tools for
      laparoscopic skills certification based on objective scoring, high availability,
      and lower cost. However, similar evaluation is lacking for robotic training. The
      purpose of this study was to assess several criteria, such as reliability, face,
      content, construct, and concurrent validity of a new virtual robotic surgery
      simulator. METHODS: This prospective study was conducted from December 2009 to
      April 2010 using three simulators dV-Trainers((r)) (MIMIC Technologies((r))) and
      one Da Vinci S((r)) (Intuitive Surgical((r))). Seventy-five subjects, divided
      into five groups according to their initial surgical training, were evaluated
      based on five representative exercises of robotic specific skills: 3D perception,
      clutching, visual force feedback, EndoWrist((r)) manipulation, and camera
      control. Analysis was extracted from (1) questionnaires (realism and interest),
      (2) automatically generated data from simulators, and (3) subjective scoring by
      two experts of depersonalized videos of similar exercises with robot. RESULTS:
      Face and content validity were generally considered high (77 %). Five levels of
      ability were clearly identified by the simulator (ANOVA; p = 0.0024). There was a
      strong correlation between automatic data from dV-Trainer and subjective
      evaluation with robot (r = 0.822). Reliability of scoring was high (r = 0.851).
      The most relevant criteria were time and economy of motion. The most relevant
      exercises were Pick and Place and Ring and Rail. CONCLUSIONS: The dV-Trainer((r))
      simulator proves to be a valid tool to assess basic skills of robotic surgery.

PMID- 22476837
TI  - Recurrence after transanal endoscopic microsurgery for large rectal adenomas.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEM) has revolutionized the
      technique and outcome of transanal surgery, becoming the standard of treatment
      for large sessile rectal adenomas. Nevertheless, only a few studies have
      evaluated the risk factors for local recurrence in order to recommend a
      "tailored" approach. The aim of this study was to identify predictor variables
      for recurrence after TEM to treat rectal adenoma. METHODS: This study is a
      retrospective analysis of a prospective database of patients treated for large
      sessile rectal adenomas by TEM at our institution, with a minimum follow-up of 12
      months. Age, gender, tumor diameter, distance from the anal verge, degree of
      dysplasia, histology, and margin involvement were investigated. RESULTS: Between
      January 1993 and July 2010, 293 patients with a rectal adenoma >=3 cm underwent
      TEM. Postoperative morbidity rate was 7.2 % (21/293) and there was no 30-day
      mortality. Over a median follow-up period of 110 (range = 12-216) months, 13
      patients (5.6 %) were diagnosed with local recurrence. The median time to
      recurrence was 10 (range = 4-33) months, with 76.9 % of recurrences detected
      within 12 months after TEM. At univariate analysis, tumor diameter (p = 0.007),
      and positive margins (p < 0.001) were shown to be significant risk factors, while
      multivariate analysis indicated the presence of positive margins as the only
      independent predictor of recurrence (p = 0.003). CONCLUSIONS: TEM provides
      excellent oncological outcomes in the treatment of large sessile benign rectal
      lesions, assuring a minimal risk of resection margin infiltration at pathology
      examination, which represents the only risk factor for recurrence.

PMID- 22476838
TI  - Recurrent laryngeal nerve injury in video-assisted thyroidectomy: lessons learned
      from neuromonitoring.
AB  - INTRODUCTION: The objective of the study was to assess the mechanism of recurrent
      laryngeal nerve (RLN) injury during video-assisted thyroidectomy (VAT). METHODS:
      The study examined 201 nerves at risk (NAR). VAT with laryngeal neuromonitoring
      (LNM) was outlined according to this scheme: (a) preparation of the operative
      space; (b) vagal nerve stimulation (V1); (c) ligature of the superior thyroid
      vessels; (d) visualization, stimulation (R1), and dissection of the RLN; (e)
      extraction of the lobe; (f) resection of the thyroid lobe; (g) final hemostasis;
      (h) verification of the electrical integrity of the RLN (V2, R2). The site,
      cause, and circumstance of nerve injury were elucidated with the application of
      LNM. Laryngeal nerve injuries were classified into type 1 injury (segmental) and
      2 (diffuse). RESULTS: Fourteen nerves (6.9 %) experienced loss of R2 and V2
      signals. 80 percent of lesions occurred in the distal 1 cm of the course of the
      RLN. The incidence of type 1 and 2 injuries was 71 and 29 % respectively. The
      mechanisms of injury were traction (70 %) and thermal (30 %). Traction lesions
      were created during the extraction of the lobe from the mini-incision [point
      (e)]. Thermal injury occurred during energy-based device use in (f) and (g)
      circumstances. CONCLUSIONS: RLN palsy still occurs with routine endoscopic
      identification of the nerve, even combined with LNM. LNM has the advantage of
      elucidating the mechanism of RLN injury. Traction and thermal RLN injuries are
      the most frequent lesions in VAT.

PMID- 22476839
TI  - Laparoscopic versus open colorectal resections in patients with symptomatic stage
      IV colorectal cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate short-term and oncologic
      outcomes of laparoscopic resection (LR) for patients with symptomatic stage IV
      colorectal cancer compared with open resection (OR). METHODS: This study is a
      retrospective analysis of a prospective database. Patients with a minimum follow
      up of 12 months after LR or OR for metastatic colorectal cancer were included.
      All analyses were performed on an "intention-to-treat" basis. RESULTS: A total of
      162 consecutive patients submitted to LR and 127 submitted to OR were included.
      In the LR group, conversion rate was 26.5 %, mostly due to locally advanced
      disease (88.4 %). A greater risk of conversion was observed among patients with a
      tumor size greater than 5 cm regardless the tumor site (P = 0.07). Early
      postoperative outcome was significantly better for LR group, with a shorter
      hospital stay (P = 0.008), earlier onset of adjuvant treatment, and similar
      postoperative complications (P = 0.853) and mortality rates (P = 0.958). LR for
      rectal cancer was associated with a higher morbidity compared with colon cancer
      (P = 0.058). During a median follow-up time of 72 months, there was no
      significant difference in overall survival between the two groups (P = 0.622).
      CONCLUSIONS: LR for symptomatic metastatic CRC is safe and, compared with OR, is
      associated with a shorter hospital stay and with similar survival rates. Concerns
      remain about LR of bulky tumors and rectal cancers due to the increased risk of
      conversion and postoperative complications.

PMID- 22476841
TI  - A sheep model for endoscopic treatment of mandible subcondylar fractures.
AB  - BACKGROUND: Mandible subcondylar fractures may be treated via a traditional
      visible access incision; however, with the advances in surgical endoscopy
      surgeons are transitioning to a minimally invasive approach in an effort to
      reduce surgical morbidity and external facial scarring. We sought to design a
      clinically applicable teaching tool in a large animal model that would allow the
      operator to gain experience treating mandible subcondylar fractures via an
      endoscopic approach. METHODS: A large animal model was developed using the Churra
      sheep. Subcondylar fractures were created, reduced, and internally plated in ten
      specimens via an extraoral, two-port endoscopic approach. Animals were monitored
      for surgical success during the intraoperative and immediate postoperative
      periods. RESULTS: Mandibles were reduced and fixated successfully in each of the
      animals. Operative time was reduced from 70 to 40 min as the surgeons became more
      familiar with the surgical procedure. Each of the ten Churra sheep used in the
      study tolerated the surgeries without postoperative complications. CONCLUSIONS:
      Capitalizing on a mandibular anatomy similar to humans, the Churra sheep
      successfully demonstrated utility for the extraoral, endoscopic approach in
      treating mandibular condyle fractures. This model offers surgeons the opportunity
      to gain surgical endoscopic experience before treating clinical patients.

PMID- 22476842
TI  - Laparoscopic versus robotic subtotal splenectomy in hereditary spherocytosis.
      Potential advantages and limits of an expensive approach.
AB  - BACKGROUND: This study was designed to compare the laparoscopic subtotal
      splenectomy with the robotic approach in patients with hereditary spherocytosis.
      METHODS: Thirty-two consecutive subtotal splenectomies by minimal approach in
      patients with hereditary spherocytosis were analyzed (10 robotic vs. 22
      laparoscopic subtotal splenectomies). RESULTS: A significant difference was found
      for the robotic approach regarding blood loss, vascular dissection duration, and
      splenic remnant size. Follow-up for 4-103 months was available. CONCLUSIONS:
      Subtotal splenectomy seems to be a suitable candidate for robotic surgery,
      requiring a delicate dissection of the splenic vessels and a correct
      intraoperative evaluation of the splenic remnant. Robotic subtotal splenectomy is
      comparable to laparoscopy in terms of hospital stay and complication. The main
      benefits are lower blood loss rate, vascular dissection time, and a better
      evaluation of the splenic remnant volume.

PMID- 22476843
TI  - No-incision (NOTES) versus single-incision (single-port) surgery for access to
      sites of peritoneal carcinomatosis: a back-to-back animal study.
AB  - BACKGROUND: Preoperative radiological diagnosis and evaluation of limited
      peritoneal carcinomatosis (PC) is suboptimal. Triangle laparoscopy is considered
      a noncarcinologic option due to the risk of tumoral spreading through the lateral
      ports into the abdominal wall muscles. Open surgery is therefore often needed to
      characterize PC. A minimally invasive approach would be progress. METHODS: We
      aimed to compare access rates to elective sites of PC using natural orifice
      transluminal endoscopic surgery (NOTES) with those using single-port laparoscopic
      surgery (SPLS). Sixteen acute experiments were performed in a live porcine model.
      Back-to-back NOTES and SPLS standardized peritoneoscopy were conducted in a cross
      over design. Access rates to 11 elective sites of PC were considered as end
      points based on operators' consensus and necropsy verification. RESULTS: Access
      to the targets was successful in 89 % with NOTES and 80 % with SPLS (p = 0.27).
      NOTES and SPLS achieved a 100 % access rate to the diaphragmatic domes and
      paracolic gutters, to the splenic area, to the pelvic floor, and to the trigonal
      bladder (p > 0.99). Access rates of NOTES versus SPLS to other elective sites of
      PC were the following: mesentery root (94 % vs. 0 %, p < 0.001), inferior
      mesenteric vein origin (88 % vs. 0 %, p < 0.001), inferior vena cava (88 % vs. 75
      %, p = 0.85), and hepatic pedicle (8 % vs. 100 %, p < 0.001). CONCLUSIONS: Both
      transgastric NOTES and SPLS provided quick and easy access to most elective sites
      of PC, except for the mesenteric vessel root (better achieved by NOTES) and the
      hepatic pedicle (better achieved by SPLS). Both techniques could be improved or
      combined to overcome their specific drawbacks.

PMID- 22476845
TI  - Electrorheology of graphene oxide.
AB  - Novel polarizable graphene oxide (GO) particles with oxidized groups on their
      edge and basal planes were prepared by a modified Hummers method, and their
      electro-responsive electrorheological (ER) characteristics when dispersed in
      silicone oil were examined with and without an electric field applied. The
      fibrillation phenomenon of this GO-based electro-responsive fluid was also
      observed via an optical microscope under an applied electric field. Both flow
      curves and dielectric spectra of the ER fluid were measured using a rotational
      rheometer and a LCR meter, respectively. Its viscoelastic properties of both
      storage and loss moduli were also examined using a vertical oscillation rheometer
      equipped with a high voltage generator, finding that the GO-based smart ER system
      behaves as a viscoelastic material under an applied electric field.

PMID- 22476844
TI  - Blood loss in cemented THA is not reduced with postoperative versus preoperative
      start of thromboprophylaxis.
AB  - BACKGROUND: Thrombin formation commences perioperatively in orthopaedic surgery
      and therefore some surgeons prefer preoperative initiation of pharmacologic
      thromboprophylaxis. However, because of the potential for increased surgical
      bleeding, the postoperative initiation of thromboprophylaxis has been advocated
      to reduce blood loss, need for transfusion, and bleeding complications. Trials on
      timing of thromboprophylaxis have been designed primarily to detect thrombotic
      events, and it has been difficult to interpret the magnitude of blood loss and
      bleeding events owing to lack of information for bleeding volume and underpowered
      bleeding end points. QUESTIONS/PURPOSES: We therefore asked whether there are
      differences in blood loss, transfusion requirements, and other postoperative
      clinical complications with preoperative versus postoperative start of
      thromboprophylaxis with dalteparin. METHODS: In a double-blind, randomized
      controlled trial, 80 patients undergoing primary cemented THA were allocated to
      dalteparin injections starting 12 hours before or 6 hours after surgery. Blood
      loss was measured by weighing sponges and drapes, volume in suction drains during
      surgery, and wound drains until removal 24 hours postoperatively. Hemoglobin and
      hematocrit were recorded at predefined times during and after surgery. RESULTS:
      We found no differences in blood loss (1081 mL +/- 424 mL versus 1023 mL +/- 238
      mL), bleeding-related events (10% versus 17%), or number of patients who had
      transfusions (12 versus five) with preoperative and postoperative
      thromboprophylaxis, respectively. Other complications were few in both groups.
      CONCLUSIONS: Our data suggest blood loss is similar with preoperative and
      postoperative initiation of dalteparin thromboprophylaxis, but indicate a trend
      toward fewer transfusion requirements which might favor postoperative start of
      thromboprophylaxis.

PMID- 22476846
TI  - Variations in feeding arteries of hepatocellular carcinoma located in the left
      hepatic lobe.
AB  - The left hepatic lobe is divided into three subsegments according to anatomical
      landmarks; however, there are several variations in the vascular territories of
      the left hepatic arterial branches. Hepatocellular carcinoma (HCC) located near
      the umbilical fissure or at the left side of the umbilical portion of the left
      portal vein has frequent crossover blood supply. HCC located in the caudal aspect
      of the lateral segment has a variety of feeding arteries, and is infrequently
      supplied by the caudate artery or the medial subsegmental artery (A4), and by the
      lateral left hepatic arteries. HCC located in the posterior aspect of segment 4
      is frequently supplied by the caudate artery or a small A4 branch arising from
      the caudate artery. In addition, the left inferior phrenic, right and left
      internal mammary, right and left gastric, cystic, and omental arteries are well
      known extrahepatic collateral pathways supplying HCC in the left hepatic lobe,
      especially when the hepatic artery is attenuated by previous transcatheter
      arterial chemoembolization (TACE). Interventional radiologists should have
      sufficient knowledge of vascular territories in the left hepatic arterial
      branches and extrahepatic collaterals to perform effective TACE for HCC located
      in the left hepatic lobe.

PMID- 22476847
TI  - Maple syrup urine disease: diffusion-weighted MRI findings during acute metabolic
      encephalopathic crisis.
AB  - Maple syrup urine disease (MSUD) is caused by a genetic defect of branched-chain
      amino acids, which include leucine, isoleucine and valine. We report diffusion
      weighted imaging (DWI) findings in a newborn child with MSUD who presented with
      acute metabolic encephalopathic crisis. DWI (b = 1,000 s/mm(2)) showed high
      signal localized within the myelinated white matter (WM) areas including the
      cerebellar white matter, pons, bulbus, cerebral peduncles, lentiform nucleus,
      posterior limbs of the internal capsules, corona radiata and bilateral
      perirolandic cortex. The apparent diffusion coefficient values of these regions
      were markedly low in the affected areas. The presence of these findings was
      considered cytotoxic or intramyelinic edema evidenced by restricted water
      diffusion. In conclusion, our findings suggest that during the acute phase and
      early encephalopathic crisis stage of MSUD, DWI can demonstrate the involvement
      of myelinated WM in newborns.

PMID- 22476848
TI  - Strigolactones: a novel class of phytohormones that inhibit the growth and
      survival of breast cancer cells and breast cancer stem-like enriched mammosphere
      cells.
AB  - Several naturally occurring phytohormones have shown enormous potential in the
      prevention and treatment of variety of different type of cancers. Strigolactones
      (SLs) are a novel class of plant hormones produced in roots and regulate new
      above ground shoot branching, by inhibiting self-renewal of undifferentiated
      meristem cells. Here, we study the effects of six synthetic SL analogs on breast
      cancer cell lines growth and survival. We show that SL analogs are able to
      inhibit proliferation and induce apoptosis of breast cancer cells but to a much
      lesser extent "non-cancer" lines. Given the therapeutic problem of cancer
      recurrence which is hypothesized to be due to drug resistant cancer stem cells,
      we also tested the ability of SL analogs to inhibit the growth of mammosphere
      cultures that are typically enriched with cancer stem-like cells. We show that
      SLs are potent inhibitors of self-renewal and survival of breast cancer cell
      lines grown as mammospheres and even a short exposure leads to irreversible
      effects on mammosphere dissociation and cell death. Immunoblot analysis revealed
      that SLs analogs induce activation of the stress response mediated by both P38
      and JNK1/2 MAPK modules and inhibits PI3K/AKT activation. Taken together this
      study indicates that SLs may be promising anticancer agents whose activities may
      be achieved through modulation of stress and survival signaling pathways.

PMID- 22476849
TI  - Rare germline large rearrangements in the BRCA1/2 genes and eight candidate genes
      in 472 patients with breast cancer predisposition.
AB  - Hereditary breast cancers account for up to 5-10 % of breast cancers and a
      majority are related to the BRCA1 and BRCA2 genes. However, many families with
      breast cancer predisposition do not carry any known mutations for BRCA1 and BRCA2
      genes. We explored the incidence of rare large rearrangements in the coding,
      noncoding and flanking regions of BRCA1/2 and in eight other candidate genes-
      CHEK2, BARD1, ATM, RAD50, RAD51, BRIP1, RAP80 and PALB2. A dedicated zoom-in CGH
      array was applied to screen for rearrangements in 472 unrelated French
      individuals from breast-ovarian cancer families that were being followed in eight
      French oncogenetic laboratories. No new rearrangement was found neither in the
      genomic regions of BRCA1/2 nor in candidate genes, except for the CHEK2 and BARD1
      genes. Three heterozygous deletions were detected in the 5' and 3' flanking
      regions of BRCA1. One large deletion introducing a frameshift was identified in
      the CHEK2 gene in two families and one heterozygous deletion was detected within
      an intron of BARD1. The study demonstrates the usefulness of CGH-array in routine
      genetic analysis and, aside from the CHEK2 rearrangements, indicates there is a
      very low incidence of large rearrangements in BRCA1/2 and in the other eight
      candidate genes in families already explored for BRCA1/2 mutations. Finally, next
      generation sequencing should bring new information about point mutations in
      intronic and flanking regions and also medium size rearrangements.

PMID- 22476850
TI  - Can diffusion-weighted MR imaging and contrast-enhanced MR imaging precisely
      evaluate and predict pathological response to neoadjuvant chemotherapy in
      patients with breast cancer?
AB  - Clinical evidence regarding the value of MRI for therapy responses assessment in
      breast cancer is increasing. The objective of this study is to compare the
      diagnostic capability of diffusion-weighted MR imaging (DW-MRI) and contrast
      enhanced MR imaging (CE-MRI) to evaluate and predict pathological response in
      breast cancer patients receiving neoadjuvant chemotherapy (NAC). We performed a
      meta-analysis of all available studies of the diagnostic performance of DW-MRI or
      CE-MRI to evaluate and predict pathological response to NAC in patients with
      breast cancer. We determined sensitivities and specificities across studies,
      calculated positive and negative likelihood ratios (LR+ and LR-), diagnostic odds
      ratio (DOR) and constructed summary receiver operating characteristic curves
      using hierarchical regression models. Methodological quality was assessed by
      QUADAS tool. Thirty-four studies met the inclusion criteria and involved 1,932
      pathologically confirmed patients in total. Methodological quality was relatively
      high. DW-MRI sensitivity was 0.93 (95 % CI 0.82-0.97) and specificity was 0.82
      (95 % CI 0.70-0.90). Overall LR+ was 5.09 (95 % CI 3.09-8.38), LR- was 0.09 (95 %
      CI 0.04-0.22), and DOR was 55.59 (95 % CI 21.80-141.80). CE-MRI sensitivity was
      0.68 (95 % CI 0.57-0.77) and specificity was 0.91 (95 % CI 0.87-0.94). Overall
      LR+ was 7.48 (95 % CI 5.29-10.57), LR- was 0.36 (95 % CI 0.27-0.48), and DOR was
      20.98 (95 % CI 13.24-33.24). Our study confirms that DW-MRI is a high sensitive
      and CE-MRI is a high specific modality in predicting pathological response to NAC
      in breast cancer patients. The combined use of DW-MRI and CE-MRI has the
      potential to improve the diagnostic performance in monitoring NAC. Further large
      prospective studies are warranted to assess the actual value of this combination
      in breast cancer preoperative treatment screening.

PMID- 22476851
TI  - MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin
      expression and is a potential prognostic marker in breast cancer.
AB  - Tumor recurrence and metastasis result in an unfavorable prognosis for cancer
      patients. Recent studies have suggested that specific microRNAs (miRNAs) may play
      important roles in the development of cancer cells. However, prognostic markers
      and the outcome prediction of the miRNA signature in breast cancer patients have
      not been comprehensively assessed. The aim of this study was to identify miRNA
      biomarkers relating to clinicopathological features and outcome of breast cancer.
      A miRNA microarray analysis was performed on breast tumors of different lymph
      node metastasis status and with different progression signatures, indicated by
      overexpression of cyclin D1 and beta-catenin genes, to identify miRNAs showing a
      significant difference in expression. The functional interaction between the
      candidate miRNA, miR-30a, and the target gene, Vim, which codes for vimentin, a
      protein involved in epithelial-mesenchymal transition, was examined using the
      luciferase reporter assay, western blotting, and migration and invasion assays.
      The association between the decreased miR-30a levels and breast cancer
      progression was examined in a survival analysis. miR-30a negatively regulated
      vimentin expression by binding to the 3'-untranslated region of Vim.
      Overexpression of miR-30a suppressed the migration and invasiveness phenotypes of
      breast cancer cell lines. Moreover, reduced tumor expression of miR-30a in breast
      cancer patients was associated with an unfavorable outcome, including late tumor
      stage, lymph node metastasis, and worse progression (mortality and recurrence) (p
      < 0.05). In conclusion, these findings suggest a role for miR-30a in inhibiting
      breast tumor invasiveness and metastasis. The finding that miR-30a downmodulates
      vimentin expression might provide a therapeutic target for the treatment of
      breast cancer.

PMID- 22476852
TI  - Targeting of mTORC2 prevents cell migration and promotes apoptosis in breast
      cancer.
AB  - Most of breast cancers are resistant to mammalian target of rapamycin complex 1
      (mTORC1) inhibitors rapamycin and rapalogs. Recent studies indicate mTORC2 is
      emerging as a promising cancer therapeutic target. In this study, we compared the
      inhibitory effects of targeting mTORC1 with mTORC2 on a variety of breast cancer
      cell lines and xenograft. We demonstrated that inhibition of mTORC1/2 by mTOR
      kinase inhibitors PP242 and OSI-027 effectively suppress phosphorylation of Akt
      (S473) and breast cancer cell proliferation. Targeting of mTORC2 either by kinase
      inhibitors or rictor knockdown, but not inhibition of mTORC1 either by rapamycin
      or raptor knockdown promotes serum starvation- or cisplatin-induced apoptosis.
      Furthermore, targeting of mTORC2 but not mTORC1 efficiently prevent breast cancer
      cell migration. Most importantly, in vivo administration of PP242 but not
      rapamycin as single agent effectively prevents breast tumor growth and induces
      apoptosis in xenograft. Our data suggest that agents that inhibit mTORC2 may have
      advantages over selective mTORC1 inhibitors in the treatment of breast cancers.
      Given that mTOR kinase inhibitors are in clinical trials, this study provides a
      strong rationale for testing the use of mTOR kinase inhibitors or combination of
      mTOR kinase inhibitors and cisplatin in the clinic.

PMID- 22476853
TI  - Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast
      cancer patients: a retrospective cohort study.
AB  - Long interspersed element 1 (LINE-1), a non-coding genomic repeat sequence,
      methylation status can influence tumor progression. In this study, the clinical
      significance of LINE-1 methylation status was assessed in primary breast cancer
      in young versus old breast cancer patients. LINE-1 methylation index (MI) was
      assessed by absolute quantitative assessment of methylated alleles (AQAMA) PCR
      assay. Initially, LINE-1 MI was assessed in a preliminary study of 235 tissues
      representing different stages of ductal breast cancer development. Next, an
      independent cohort of 379 primary ductal breast cancer patients (median follow-up
      18.9 years) was studied. LINE-1 hypomethylation was shown to occur in DCIS and
      invasive breast cancer. In primary breast cancer it was associated with
      pathological tumor stage (p = 0.026), lymph node metastasis (p = 0.022), and
      higher age at diagnosis (>55, p < 0.001). In multivariate analysis, LINE-1
      hypomethylation was associated with decreased OS (HR 2.19, 95 % CI 1.17-4.09, log
      rank p = 0.014), DFS (HR 2.05, 95 % CI 1.14-3.67, log-rank p = 0.016) and
      increased DR (HR 2.83, 95 % CI 1.53-5.21, log-rank p = 0.001) in younger (<=55
      years), but not older patients (>55 years). LINE-1 analysis of primary breast
      cancer demonstrated cancer-related age-dependent hypomethylation. In patients
      <=55 years, LINE-1 hypomethylation portends a high-risk of DR.

PMID- 22476854
TI  - High-sensitivity C-reactive protein (hs-CRP) as a biomarker for trastuzumab
      induced cardiotoxicity in HER2-positive early-stage breast cancer: a pilot study.
AB  - Monitoring of left ventricular ejection fraction (LVEF) is the current standard
      for detection of trastuzumab-induced cardiotoxicity; however, time-to-diagnosis
      and cost of assessment are suboptimal in women with early-stage breast cancer. We
      assessed the utility of B-type natriuretic peptide (BNP), high-sensitivity C
      reactive protein (hs-CRP), and cardiac troponin I (cTnI) as serum biomarkers for
      early detection of trastuzumab-induced cardiotoxicity. Fifty-four women with
      human epidermal growth factor receptor 2 (HER2)-positive early-stage breast
      cancer were prospectively enrolled, and the relationship between elevated serum
      BNP, hs-CRP, and cTnI levels and clinically significant decreases in LVEF was
      examined. LVEF was monitored at 3-4 month intervals during trastuzumab treatment.
      Laboratory testing for candidate biomarkers was repeated every 3 weeks with each
      cycle of trastuzumab. Trastuzumab-induced cardiotoxicity was defined as a
      decrease in LVEF of >=15% or to a value below 50%. A clinically significant
      decrease in LVEF was observed in 28.6% of women. Abnormal hs-CRP (>=3 mg/L)
      predicted decreased LVEF with a sensitivity of 92.9% (95% CI 66.1-99.8) and
      specificity of 45.7% (95% CI 28.8-63.4), and subjects with normal hs-CRP levels
      (<3 mg/L) have 94.1% negative predictive 94.1% (95% CI 70.3-99.9) suggesting that
      normal hs-CRP levels may be associated with low future risk for decreased LVEF;
      however, no association with BNP or cTnI was observed. A false positive would
      have a relatively low associated cost in breast cancer patients undergoing
      adjuvant trastuzumab therapy and would indicate continuation of routine
      observation during treatment through traditional means. The maximum hs-CRP value
      was observed a median of 78 days prior to detection of cardiotoxicity by
      decreased LVEF, and those with normal levels were at lower risk for
      cardiotoxicity. Regular monitoring of hs-CRP holds promise as a biomarker for
      identifying women with early-stage breast cancer at low risk for asymptomatic
      trastuzumab-induced cardiotoxicity. To our knowledge, this is the first study
      documenting the utility of a less expensive, reproducible, easily obtainable
      biomarker with rapid results for evaluating cardiotoxicity related to trastuzumab
      therapy.

PMID- 22476855
TI  - Notch2 activation by benzyl isothiocyanate impedes its inhibitory effect on
      breast cancer cell migration.
AB  - Benzyl isothiocyanate (BITC) is a promising anticancer constituent of edible
      cruciferous vegetables with in vivo efficacy against chemically induced as well
      as oncogene-driven breast cancer in experimental rodents. However, the mechanism
      underlying anticancer effect of BITC is not fully understood. This study was
      undertaken to determine the role of Notch signaling in anticancer responses to
      BITC as this pathway is often hyperactive in human breast cancer. Exposure of MCF
      7, MDA-MB-231, and SUM159 human breast cancer cells to pharmacologic
      concentrations of BITC (2.5 and 5 MUM) resulted in cleavage (activation) of
      Notch1, Notch2, and Notch4, which was accompanied by induction of gamma-secretase
      complex components Presenilin1 and/or Nicastrin. The BITC-mediated cleavage of
      Notch was associated with its transcriptional activation as revealed by RBP-Jk
      and Hes-1A/B luciferase reporter assays. Inhibition of cell migration or cell
      viability resulting from BITC exposure was not influenced by pharmacological
      suppression of Notch1 using a gamma-secretase inhibitor or RNA interference of
      Notch1 as well as Notch4. On the other hand, the BITC-mediated inhibition of cell
      migration, but not cell viability, was significantly augmented by siRNA and shRNA
      knockdown of Notch2 protein. Furthermore, the BITC-mediated inhibition of MDA-MB
      231 xenograft growth in vivo was associated with a significant increase in
      nuclear levels of cleaved Notch2 and Hes-1 proteins. In conclusion, the results
      of this study indicate that (a) BITC treatment activates Notch2 in cultured and
      xenografted human breast cancer cells, and (b) Notch2 activation impedes
      inhibitory effect of BITC on cell migration.

PMID- 22476856
TI  - Final results of a multicenter phase II clinical trial evaluating the activity of
      single-agent lapatinib in patients with HER2-negative metastatic breast cancer
      and HER2-positive circulating tumor cells. A proof-of-concept study.
AB  - This multicenter phase II trial was designed to evaluate the activity of
      lapatinib in metastatic breast cancer patients with HER2-negative primary tumors
      and HER2-positive circulating tumor cells (CTCs). In this study MBC patients with
      HER2-negative primary tumors and HER2-positive CTCs previously treated with at
      least a first-line therapy for metastatic disease received lapatinib 1500 mg/day.
      The CellSearch System(r) was used for CTCs isolation and bio-characterization.
      HER2 status was assessed on CTCs by immunofluorescence. A case was defined as
      CTCs positive if >=2 CTC/7.5 ml of blood were isolated and HER2-positive if >=50%
      of CTCs were HER2-positive. 139 HER2-negative patients were screened, 96 patients
      were positive for CTCs (mean number of CTCs: 85; median number of CTCs: 19; range
      2-1637). Seven of the 96 patients (7%) had >=50% HER2-positive CTCs and were
      eligible for treatment with lapatinib. No objective tumor responses occurred in
      this population. In one patient, disease stabilization lasting 254 days (8.5
      months) was observed. From the findings of this study, we concluded that a subset
      of patients with a HER2-negative primary tumor presents HER2-positive CTCs during
      disease progression, although the HER2 shift rate seems to be lower than
      previously reported. Despite the lack of objective response, the durable disease
      stabilization observed in one patient cannot rule out the hypothesis that
      lapatinib may have some activity in this patient population. However, considering
      that only 1/139 screened patients may potentially have derived benefit from this
      approach, future trials designed according to the presented strategy cannot be
      recommended.

PMID- 22476857
TI  - Genetic heterogeneity of HER2 in breast cancer: impact on HER2 testing and its
      clinicopathologic significance.
AB  - In 2009, ASCO/CAP expanded its human epidermal growth factor receptor type 2
      (HER2) testing guideline to define HER2 genetic heterogeneity (GH). However, the
      clinical significance of GH is unclear. We investigated the impact of HER2 GH on
      HER2 testing and studied its clinicopathologic significance. Paraffin-embedded
      tumor tissues of surgical resections of 617 non-consecutive breast carcinoma
      patients were studied by routine HER2 fluorescence in situ hybridization (FISH).
      HER2 GH was evaluated, and the results were correlated with HER2 protein
      expression by immunohistochemistry and HER2 gene amplification by FISH, and with
      various clinicopathologic parameters. HER2 GH was observed in 15.2 % (94/617) of
      the patients. It was associated with low-to-middle level of HER2 expression, and
      with none-to-low level of HER2 gene amplification. Among the 17 patients with
      equivocal HER2 FISH results, 35.3 % (6/17) of tumors displayed GH. In contrast
      with HER2-positive tumors without GH, tumors with HER2 GH demonstrated
      significant association with lower histologic grade, smaller tumor size, and
      proclivity to hormone receptor expression. HER2 GH is a substantial cause of
      equivocal HER2 testing results of breast cancer by FISH. Tumors with HER2 GH
      showed that biologic features resemble more of HER2-negative tumors than HER2
      positive tumors without GH. The findings indicate a need of the guidelines to
      clarify whether tumors with HER2 GH truly benefit from HER2-targeted therapy of
      breast cancer.

PMID- 22476858
TI  - Impact of the positive pathergy test on the performance of
      classification/diagnosis criteria for Behcet's disease.
AB  - BACKGROUND: The only diagnostic test that currently exists for Behcet's disease
      (BD) is the pathergy test. A positive pathergy test (PPT) is an important
      component of many of the 16 sets of classification/diagnosis criteria used to
      diagnose BD. The aim of this study was to determine the importance of a PTT in
      the performance of the diagnosis/classification criteria for BD. PATIENTS AND
      METHODS: All patients listed in the BD registry of the Rheumatology Research
      Center, Tehran (6,727) and 4,648 BD controls were enrolled in the study. The
      diagnosis was clinical when no other diagnosis could explain the patient's
      manifestations. The criteria were tested with and without PPT results.
      Sensitivity, specificity, and accuracy were calculated. RESULTS: Without PPT, all
      sets of criteria lost sensitivity, gained specificity, and lost accuracy, with
      the exception of the Cheng-Zhang criteria. The largest loss in sensitivity was
      for the Hubault-Hamza (35 %) and Dilsen (17.3 %) criteria; the least was for the
      Curth (1.9 %) and ICBD (6.5 %) criteria. The largest gain on specificity was for
      the Dilsen (4.7 %) and Curth (3.1 %) criteria; the least was for the Japan (0.1
      %) and Japan revised (0.1 %) criteria. The greatest loss in accuracy was for the
      Hubault-Hamza (20.4 %) and Dilsen revised (9.3 %) criteria; the least was for the
      ICBD (3.6 %), while Curth gained 0.3 %. CONCLUSION: Without PPT as a criterion
      for the diagnosis of BD, the sensitivity and accuracy of the sets of
      classification/diagnosis criteria decrease, while the specificity improves.

PMID- 22476859
TI  - Recurrent laryngeal nerve.

PMID- 22476860
TI  - Conservative management of post-transplant central nervous system lymphoma.
AB  - Primary CNS lymphoma (PCNSL) is a rare B cell variant non-Hodgkins lymphoma that
      is confined to the brain, leptomeninges, spinal cord and eyes. Its incidence is
      increasing, primarily due to increase in the number of organ transplantations
      being undertaken. The majority of the PTLD (post-transplant lymphoproliferative
      disorder) is seen in kidney transplant recipients simply because they constitute
      a larger group of transplant recipients each year as compared to other solid
      organ transplantations. Primary infection of previously infected EBV seronegative
      patients and immunosuppression are found to be the main etiologic factors in the
      development of PTLD-PCNSL. There are no clear guidelines on treatment regimens,
      and it should be individualized according to patient comorbidities. We report a
      case of PCNS lymphoproliferative disorder in a kidney transplant recipient, which
      underwent complete remission with decreasing immunosuppression. The patient could
      not undergo chemotherapy/radiotherapy due to underlying comorbidities. We
      highlight the available treatment modalities for PTLD-PCNSL. 

PMID- 22476861
TI  - Altered ventriculo-arterial coupling during exercise in athletes releasing
      biomarkers after endurance running.
AB  - Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and
      N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood
      phenomenon proposed to especially occur with high-intensity exercise in less
      trained subjects. We hypothesised that haemodynamic perturbations during exercise
      are larger in athletes with cTnT release, and studied athletes with detectable
      cTnT levels after an endurance event (HIGH; n = 16; 46 +/- 9 years) against
      matched controls whose levels were undetectable (LOW; n = 11; 44 +/- 7 years).
      Echocardiography was performed at rest and at peak supine bicycle exercise
      stress. Left ventricular (LV) end-systolic elastance (E (LV) a load-independent
      measure of LV contractility), effective arterial elastance (E (A) a lumped index
      of arterial load) and end-systolic meridional wall stress were calculated from
      cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was
      judged from the ventriculo-arterial coupling ratio (E (A)/E (LV): optimal range
      0.5-1.0). While subgroups had similar values at rest, we found ventriculo
      arterial mismatch during exercise in HIGH subjects [0.47 (0.39-0.58) vs. LOW:
      0.73 (0.62-0.83); p < 0.01] due to unopposed increase in E (LV) (p < 0.05). In
      LOW subjects, a greater increase occurred in E (A) during exercise (+81 +/- 67 %
      vs. HIGH: +39 +/- 32 %; p = 0.02) which contributed to a maintained coupling
      ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress
      during exercise (R (2) = 0.39; p < 0.01) despite no correlation at rest (p = ns).
      In conclusion, athletes with exercise-induced biomarker release exhibit
      ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work
      may contribute to this phenomenon.

PMID- 22476862
TI  - Ciprofibrate regulation of rat hepatic bilirubin glucuronidation and UDP
      glucuronosyltransferases expression.
AB  - Synthetic fibrates are hypolipidemic drugs known to stimulate hepatic peroxisome
      proliferation and bilirubin glucuronidation. This study was designed to estimate
      the effects of ciprofibrate simultaneously on rat hepatic bilirubin
      glucuronoconjugation and on hepatic expression of UGT1A1, UGT1A2 and UGT1A5, all
      of which belong to the bilirubin cluster. Hepatic bilirubin glucuronidation
      activity and UDP-glucuronosyltransferase expression (RT-PCR and Western blotting)
      were measured after a single-dose ciprofibrate treatment (5 mg/kg by gastric
      intubation) in 36-h time course experiments. Ciprofibrate regulation of PPARalpha
      and UGT1A5 mRNA expression was also investigated in rat hepatocytes. Bilirubin
      conjugation activity was induced by ciprofibrate, reaching a maximum level (2.4*)
      24 h after the treatment. UGT1A1 and UGT1A5 mRNA expression was induced 1.5 times
      by ciprofibrate, with UGT1A5 reaching the basal level of UGT1A1. Although UGT1A2
      mRNA was induced approximately threefold by ciprofibrate, its expression level
      remained low in comparison with basal or induced levels of UGT1A1 and UGT1A5
      mRNA. In the 36-h time course experiment, bilirubin conjugation activity as well
      as UGT1A5 and PPARalpha mRNA expression presented a biphasic induction profile.
      Although a similar level of induction was observed in primary cultured hepatocyte
      experiments, such biphasic variation was not observed for both UGT1A5 and
      PPARalpha, and the induction of UGT1A5 mRNA expression by ciprofibrate required
      de novo protein synthesis. A single dose of ciprofibrate significantly induces
      rat liver bilirubin conjugation as well as UGT1A1, UGT1A5 and PPARalpha
      expression. The induction mechanism may involve PPARalpha, at least regarding
      UGT1A5 regulation.

PMID- 22476863
TI  - E2F1 induces p19INK4d, a protein involved in the DNA damage response, following
      UV irradiation.
AB  - Central to the maintenance of genomic integrity is the cellular DNA damage
      response. Depending on the type of genotoxic stress and through the activation of
      multiple signaling cascades, it can lead to cell cycle arrest, DNA repair,
      senescence, and apoptosis. p19INK4d, a member of the INK4 family of CDK
      inhibitors, plays a dual role in the DNA damage response, inhibiting cell
      proliferation and promoting DNA repair. Consistently, p19INK4d has been reported
      to become upregulated in response to UV irradiation and a great variety of
      genotoxic agents. Here, this induction is shown to result from a transcriptional
      stimulatory mechanism that can occur at every phase of the cell cycle except
      during mitosis. Moreover, evidence is presented that demonstrates that E2F1 is
      involved in the induction of p19INK4d following UV treatment, as it is prevented
      by E2F1 protein ablation and DNA-binding inhibition. Specific inhibition of this
      regulation using triplex-forming oligonucleotides that target the E2F response
      elements present in the p19INK4d promoter also block p19INK4d upregulation and
      sensitize cells to DNA damage. These results constitute the first description of
      a mechanism for the induction of p19INK4d in response to UV irradiation and
      demonstrate the physiological relevance of this regulation following DNA damage.

PMID- 22476864
TI  - SNARE proteins are not excessive for the formation of post-Golgi SNARE complexes
      in HeLa cells.
AB  - To evaluate the role of SNARE proteins in the constitutive exocytosis, we knocked
      down syntaxin 3, 4, 5, 6, 7, and VAMP3, 5, 7, 8 with their siRNAs, and determined
      the cell-to-medium ratio of CLuc, a secreted luciferase of Cypridina noctiluca.
      Although the protein level of SNAREs in HeLa cells was markedly reduced by the
      siRNA treatment, the cell/medium ratio was scarcely increased by any siRNAs
      except for syntaxin 5. The accumulation of GFP-tagged human growth hormone was
      also visible only by the knockdown of syntaxin 5. To examine whether the residual
      amount of SNAREs are sufficient for maintaining normal constitutive exocytosis,
      we estimated the effect of siRNAs on the level of post-Golgi SNARE complexes
      containing syntaxin 4, SNAP23, and VAMP3 or VAMP8. The amount of SNARE complexes
      was robustly decreased by siRNAs and was well correlated with the residual amount
      of SNAREs in the lysates, suggesting that SNAREs are unnecessarily excessive for
      the formation of post-Golgi SNARE complexes in HeLa cells.

PMID- 22476865
TI  - Anxiety as predictor of the cortisol awakening response in patients with coronary
      heart disease.
AB  - BACKGROUND: Anxiety is associated with worse outcomes in patients with coronary
      heart disease (CHD). A dysregulation of the HPA axis is a potential mechanism
      linking psychological factors and coronary disease. No study has yet investigated
      the relationship between anxiety and cortisol among patients with established
      CHD. PURPOSE: The aim of this study was to assess the association between anxiety
      and the cortisol awakening response in patients with CHD. METHOD: Four salivary
      cortisol samples were used to assess two measures of the cortisol awakening
      response (CAR) in 47 patients with established CHD. Anxiety was measured using
      the Hospital Anxiety and Depression Scale (HADS). RESULTS: Higher anxiety values
      were associated with a higher total output of cortisol in the first hour after
      awakening (AUCg, area under the curve with respect to ground) (p = 0.04) and a
      nonsignificant trend towards a more pronounced increase (AUCi, area under the
      curve with respect to increase) (p = 0.08). In patients who had a history of
      myocardial infarction (MI), the cortisol output was lower compared to patients
      who had no previous MI (p = 0.02). In linear regression analyses, anxiety emerged
      as significant predictor of AUCg and AUCi after controlling for MI, ejection
      fraction (LVEF, left ventricular ejection fraction), and depression. CONCLUSIONS:
      Our results provide further indications for an association between anxiety and a
      dysregulation of the HPA axis. History of MI emerged as second predictor of
      cortisol output in the morning.

PMID- 22476866
TI  - Factors predicting recurrence of chronic subdural haematoma: the influence of
      intraoperative irrigation and low-molecular-weight heparin thromboprophylaxis.
AB  - BACKGROUND: Burr-hole drainage has become the accepted treatment of choice for
      chronic subdural haematoma (cSDH), although still burdened with a major
      recurrence rate. The current analysis was initiated to determine management
      related risk factors for recurrence, i.e. postoperative low-molecular-weight
      heparin thromboprophylaxis, and the importance of rinsing the subdural space.
      METHODS: Two-hundred and forty-seven patients with computerised tomography (CT)
      defined symptomatic cSDH were managed by two burr-hole trepanations and drainage
      between January 2005 and November 2008. Postoperative thromboprophylaxis with 40
      mg enoxaparine daily was given only during the first half of the study period.
      For the current analysis the amount of rinsing fluid, postoperative low-dose
      thromboprophylaxis, as well as age and gender, bilaterality, preoperative and
      postoperative blood coagulation studies, platelet counts and decrease of subdural
      fluid on early postoperative CT, were recorded and correlated with recurrence.
      Statistical calculation was done by univariate and multivariate analysis.
      RESULTS: A total of 62 of 247 patients needed revision surgery for recurrence
      (25.1 %). Recurrence rates were significantly lower in the patients treated
      without postoperative enoxaparine (18.84 %) than in the group with postoperative
      low-dose enoxaparine thromboprophylaxis (32.11 %) and enoxaparine was
      administered in a higher proportion of the patients suffering recurrence (P =
      0.013). A median intraoperative irrigation volume of 863 ml saline was used in
      the patients suffering recurrence and 1,500 ml in patients without recurrence (P
      < 0.001). The median age was slightly higher in the patients suffering from
      recurrence. Male gender predominated in both groups but was slightly more
      pronounced in the recurrence group. Preoperative and postoperative platelet
      counts and plasmatic coagulation indices did not differ significantly between the
      groups. Relative residual subdural fluid collection on early postoperative CT
      remained larger in patients finally suffering recurrence (P = 0.03). Multivariate
      analysis confirmed a small amount of rinsing fluid, male gender and the use of
      enoxaparine as the most important risk factors for recurrence, although that
      latter factor did not reach statistical significance in the multivariate
      analysis. CONCLUSIONS: The investigation provides evidence that copious
      intraoperative irrigation and avoidance of postoperative low-molecular-weight
      heparin thromboprophylaxis may reduce the recurrence rate of cSDH.

PMID- 22476867
TI  - Enamel lesion parameter correlations between polychromatic micro-CT and TMR.
AB  - Transverse microradiography (TMR) is considered as the gold standard technique
      for the evaluation of enamel lesions. Micro-computed tomography (uCT) has the
      advantage of non-destructive measurements, but the beam-hardening effect with
      polychromatic x-rays is a major drawback. To date, no study has validated uCT
      against TMR. The objective of this study was to validate uCT measurements of
      enamel lesions under various x-ray conditions and software beam-hardening
      correction (BHC) against TMR. Human molars with natural white-spot lesions were
      scanned for 5 min by uCT at 100 kV in different conditions: 50 uA (0.5-mm Al
      filter), 165 uA (0.5-mm Al/0.3-mm Cu), and 200 uA (0.5-mm Al/0.4-mm Cu), with or
      without BHC. Grayscale values were converted into mineral density values using
      phantoms. Thin sections at the same positions were then prepared for TMR. Lesion
      depth (LD; um) and mineral loss (DeltaZ; vol%um) were compared between uCT and
      TMR by Pearson's correlations. uCT measurements correlated well with TMR under
      all conditions (p < 0.001, r > 0.86 for LD and DeltaZ), except for 0.5-mm Al
      without BHC (p > 0.05). Even without BHC, combined Al/Cu filters successfully
      reduced the beam-hardening effect. uCT can be used as a non-destructive
      alternative to TMR with comparable parameters for the study of enamel lesions.

PMID- 22476868
TI  - Cytokine expression in the colostral cells of healthy and allergic mothers.
AB  - There is no doubt about the beneficial effect of breastfeeding on the newborn's
      immune system. It is not fully elucidated what the differences are between the
      colostrum/milk of healthy and allergic mothers and how beneficial breastfeeding
      by an allergic mother is. The gene expression of selected cytokines was tested in
      cells isolated from colostra of healthy and allergic mothers using quantitative
      real-time PCR. Allergic phenotype was evident in colostral cells of allergic
      mothers: gene expressions of IL-4, IL-13 and EGF were increased and those of IFN
      gamma decreased in comparison with colostral cells of healthy mothers. The
      allergic phenotype of the colostral cells of allergic mothers supporting the bias
      to a Th2 type response was found. It remains a question if a small number of
      these cells could influence the immature newborn immune system.

PMID- 22476869
TI  - The role of the electroencephalogram as a tool for the investigation of syncope.

PMID- 22476871
TI  - Abstracts of the 6th cachexia conference, milan, Italy, december 8-10, 2011.

PMID- 22476870
TI  - Cloning, in silico characterization and prediction of three dimensional structure
      of SbDof1, SbDof19, SbDof23 and SbDof24 proteins from Sorghum [Sorghum bicolor
      (L.) Moench].
AB  - In the present study, four full-length Dof (DNA-binding with one finger) genes
      from Sorghum bicolor namely SbDof1, SbDof19, SbDof23, and SbDof24 were PCR
      amplified, gel eluted, cloned, and sequenced (accession number HQ540084,
      HQ540085, HQ540086, and HQ540087, respectively). These sequences were further
      characterized in silico by subjecting them to homology search, multiple sequence
      alignment, phylogenetic tree construction, and protein functional analysis,
      revealing their identity to Dof like proteins. Phylogenetic analysis of cloned
      SbDof genes along with other reported Dof proteins revealed existence of two
      major groups A and B, while group A was further bifurcated into two sub-groups
      (viz., I and II). Motif scan analysis of SbDof proteins revealed the presence of
      glycine- and alanine-rich profiles in SbDof1, while proline-rich profile was
      observed in SbDof23. Asparagines, methionine, and serine-rich profiles were
      common in case of both SbDof19 and SbDof24 proteins. The three dimensional
      structures of SbDof proteins were predicted by I-TASSER server based on multiple
      threading method. The modeled structures were refined by energy minimization and
      their stereo chemical qualities were validated by PROCHECK and QMEAN server
      indicating the acceptability of the predicted models. The final models were
      submitted to PMDB database with assigned PMDB IDs, i.e., PM0077395, PM0077396,
      PM0077397, PM0077398, and PM0076448 for SbDof1, SbDof19, SbDof23, SbDof24, and
      Dof domain, respectively. Based on gene ontology (GO) terms in I-TASSER server
      putative functions of modeled SbDof proteins were also predicted.

PMID- 22476872
TI  - [Laparoscopic versus endoscopic primary management of choledocholithiasis. A
      retrospective case-control study].
AB  - BACKGROUND: The aim was to present the long-term results of one-stage
      laparoscopic procedure for the management of common bile duct (CBD) lithiasis in
      comparison with the primary endoscopic approach via ERCP. PATIENTS AND METHODS: A
      retrospective case-control study was performed to determine the outcome of
      patients treated for CBD lithiasis (04/1997 - 11/2011). Data of patients with
      choledocholithiasis undergoing the two treatment modalities - laparoscopic common
      bile duct exploration plus laparoscopic cholecystectomy (LCBDE + LC, group A, n =
      101) versus endoscopic retrograde cholangiopancreatography/sphincterotomy and
      laparoscopic cholecystectomy (ERCP/S + LC, group B, n = 116) were matched
      according to their clinical characteristics. Patients of group A underwent either
      laparoscopic choledochotomy or transcystic exploration. The policy was to convert
      to open choledochotomy only after the sequential application of the two treatment
      modalities (laparoscopic/endoscopic procedure) had failed. RESULTS: No
      significant difference in morbidity was found between the groups (group A 8%
      versus group B 11.2%). Conversion to another procedure was mandatory in 12 out of
      101 and 17 out of 116 patients of groups A and B, respectively. The mean follow
      up period was 7.8 years (range 1-12 years). Effective laparoscopic treatment of
      CBD stones (cholecystectomy and CBD clearance) was possible in 89 of the 101
      patients in group A (88.1%) compared with 99 of the 116 patients in group B
      (85.4%) after the endoscopic approach. CONCLUSIONS: This study showes that both -
      primary endoscopy and one-stage laparoscopic management of CBD lithiasis - are
      highly effective and safe with comparable results.

PMID- 22476873
TI  - Combinations of mutant FAD2 and FAD3 genes to produce high oleic acid and low
      linolenic acid soybean oil.
AB  - High oleic acid soybeans were produced by combining mutant FAD2-1A and FAD2-1B
      genes. Despite having a high oleic acid content, the linolenic acid content of
      these soybeans was in the range of 4-6 %, which may be high enough to cause
      oxidative instability of the oil. Therefore, a study was conducted to incorporate
      one or two mutant FAD3 genes into the high oleic acid background to further
      reduce the linolenic acid content. As a result, soybean lines with high oleic
      acid and low linolenic acid (HOLL) content were produced using different sources
      of mutant FAD2-1A genes. While oleic acid content of these HOLL lines was stable
      across two testing environments, the reduction of linolenic acid content varied
      depending on the number of mutant FAD3 genes combined with mutant FAD2-1 genes,
      on the severity of mutation in the FAD2-1A gene, and on the testing environment.
      Combination of two mutant FAD2-1 genes and one mutant FAD3 gene resulted in less
      than 2 % linolenic acid content in Portageville, Missouri (MO) while four mutant
      genes were needed to achieve the same linolenic acid in Columbia, MO. This study
      generated non-transgenic soybeans with the highest oleic acid content and lowest
      linolenic acid content reported to date, offering a unique alternative to produce
      a fatty acid profile similar to olive oil.

PMID- 22476874
TI  - QTL mapping of terminal heat tolerance in hexaploid wheat (T. aestivum L.).
AB  - High temperature (>30  degrees C) at the time of grain filling is one of the
      major causes of yield reduction in wheat in many parts of the world, especially
      in tropical countries. To identify quantitative trait loci (QTL) for heat
      tolerance under terminal heat stress, a set of 148 recombinant inbred lines was
      developed by crossing a heat-tolerant hexaploid wheat (Triticum aestivum L.)
      cultivar (NW1014) and a heat-susceptible (HUW468) cultivar. The F(5), F(6), and
      F(7) generations were evaluated in two different sowing dates under field
      conditions for 2 years. Using the trait values from controlled and stressed
      trials, four different traits (1) heat susceptibility index (HSI) of thousand
      grain weight (HSITGW); (2) HSI of grain fill duration (HSIGFD); (3) HSI of grain
      yield (HSIYLD); and (4) canopy temperature depression (CTD) were used to
      determine heat tolerance. Days to maturity was also investigated. A linkage map
      comprising 160 simple sequence repeat markers was prepared covering the whole
      genome of wheat. Using composite interval mapping, significant genomic regions on
      2B, 7B and 7D were found to be associated with heat tolerance. Of these, two (2B
      and 7B) were co-localized QTL and explained more than 15 % phenotypic variation
      for HSITGW, HSIGFD and CTD. In pooled analysis over three trials, QTL explained
      phenotypic variation ranging from 9.78 to 20.34 %. No QTL * trial interaction was
      detected for the identified QTL. The three major QTL obtained can be used in
      marker-assisted selection for heat stress in wheat.

PMID- 22476875
TI  - Patterns of linkage disequilibrium and association mapping in diploid alfalfa (M.
      sativa L.).
AB  - Association mapping enables the detection of marker-trait associations in
      unstructured populations by taking advantage of historical linkage disequilibrium
      (LD) that exists between a marker and the true causative polymorphism of the
      trait phenotype. Our first objective was to understand the pattern of LD decay in
      the diploid alfalfa genome. We used 89 highly polymorphic SSR loci in 374
      unimproved diploid alfalfa (Medicago sativa L.) genotypes from 120 accessions to
      infer chromosome-wide patterns of LD. We also sequenced four lignin biosynthesis
      candidate genes (caffeoyl-CoA 3-O-methyltransferase (CCoAoMT), ferulate-5
      hydroxylase (F5H), caffeic acid-O-methyltransferase (COMT), and phenylalanine
      amonialyase (PAL 1)) to identify single nucleotide polymorphisms (SNPs) and infer
      within gene estimates of LD. As the second objective of this study, we conducted
      association mapping for cell wall components and agronomic traits using the SSR
      markers and SNPs from the four candidate genes. We found very little LD among SSR
      markers implying limited value for genomewide association studies. In contrast,
      within gene LD decayed within 300 bp below an r (2) of 0.2 in three of four
      candidate genes. We identified one SSR and two highly significant SNPs associated
      with biomass yield. Based on our results, focusing association mapping on
      candidate gene sequences will be necessary until a dense set of genome-wide
      markers is available for alfalfa.

PMID- 22476876
TI  - Impact of the quantity and flavonoid content of fruits and vegetables on markers
      of intake in adults with an increased risk of cardiovascular disease: the FLAVURS
      trial.
AB  - PURPOSE: Limited robust randomised controlled trials investigating fruit and
      vegetable (F&V) intake in people at risk of cardiovascular disease (CVD) exist.
      We aimed to design and validate a dietary strategy of increasing flavonoid-rich
      versus flavonoid-poor F&V consumption on nutrient biomarker profile. METHODS: A
      parallel, randomised, controlled, dose-response dietary intervention study.
      Participants with a CVD relative risk of 1.5 assessed by risk scores were
      randomly assigned to one of the 3 groups: habitual (control, CT), high-flavonoid
      (HF) or low-flavonoid (LF) diets. While the CT group (n = 57) consumed their
      habitual diet throughout, the HF (n = 58) and LF (n = 59) groups sequentially
      increased their daily F&V intake by an additional 2, 4 and 6 portions for 6-week
      periods during the 18-week study. RESULTS: Compliance to target numbers and types
      of F&V was broadly met and verified by dietary records, and plasma and urinary
      biomarkers. Mean (+/- SEM) number of F&V portions/day consumed by the HF and LF
      groups at baseline (3.8 +/- 0.3 and 3.4 +/- 0.3), 6 weeks (6.3 +/- 0.4 and 5.8 +/
      0.3), 12 weeks (7.0 +/- 0.3 and 6.8 +/- 0.3) and 18 weeks (7.6 +/- 0.4 and 8.1
      +/- 0.4), respectively, was similar at baseline yet higher than the CT group (3.9
      +/- 0.3, 4.3 +/- 0.3, 4.6 +/- 0.4, 4.5 +/- 0.3) (P = 0.015). There was a dose
      dependent increase in dietary and urinary flavonoids in the HF group, with no
      change in other groups (P = 0.0001). Significantly higher dietary intakes of
      folate (P = 0.035), non-starch polysaccharides (P = 0.001), vitamin C (P =
      0.0001) and carotenoids (P = 0.0001) were observed in both intervention groups
      compared with CT, which were broadly supported by nutrient biomarker analysis.
      CONCLUSIONS: The success of improving nutrient profile by active encouragement of
      F&V intake in an intervention study implies the need for a more hands-on public
      health approach.

PMID- 22476877
TI  - Discrete phosphorylated retinoblastoma protein isoform expression in mouse tooth
      development.
AB  - Retinoblastoma protein (pRb) phosphorylation plays a central role in mediating
      cell cycle G1/S stage transition, together with E2F transcription factors. The
      binding of pRb to E2F is thought to be controlled by the sequential and
      cumulative phosphorylation of pRb at various amino acids. In addition to well
      characterized roles as a tumor suppressor, pRb has more recently been implicated
      in osteoprogenitor and other types of stem cell maintenance, proliferation and
      differentiation, thereby influencing the morphogenesis of developing organs. In
      this study, we present data characterizing the expression of pRb and three
      phosphorylated pRb (ppRb) isoforms-ppRbS780, ppRbS795, ppRbS807/811-in
      developmentally staged mouse molar and incisor teeth. Our results reveal distinct
      developmental expression patterns for individual ppRb isoforms in dental
      epithelial and dental mesenchymal cell differentiation, suggesting discrete
      functions in tooth development.

PMID- 22476878
TI  - Artificial liver support system reduces intracranial pressure more effectively
      than bioartificial system: an experimental study.
AB  - OBJECTIVES: Extracorporeal liver support (ELS) may play a role in bridging
      therapy in patients with acute liver failure (ALF). The aim of this study was to
      compare the influence of nonbiological and biological methods on intracranial
      pressure (ICP) in an animal model of ALF. METHODS: A surgical devascularization
      model of ALF in pigs (35-40 kg) was used. Elimination therapy started after the
      onset of hypoglycemia. Biochemical parameters (bilirubin, ammonia, lactate, etc.)
      as well as ICP and cerebral perfusion pressure (CPP) were monitored for 12 hours.
      Of the total 31 pigs with ALF, 14 animals were treated by fractionated plasma
      separation and absorption (FPSA), 10 were treated with a bioartificial liver
      (BAL), and 7 animals were used as a control group. RESULTS: FPSA and BAL
      treatment started on average 3 hours 17 minutes and 2 hours 21 minutes, after
      devascularization and lasted for 5 hours 54 minutes and 5 hours 43 minutes,
      respectively. Ammonia levels were lower in the FPSA group, and bilirubin levels
      differed significantly in both the FPSA and BAL groups compared with controls.
      However, ICP values were reduced more effectively in pigs treated by FPSA: 19.1
      vs. 27.0 mm Hg at 9 hours, 22.5 vs. 28.7 mm Hg at 11 hours, and 24.0 vs. 33.0 mm
      Hg at 12 hours (p<0.05). CONCLUSIONS: The artificial liver support system FPSA
      reduced ICP values more effectively than the Performer O. Liver RanD BAL system.
      Compared with this BAL system, the nonbiological elimination method of FPSA is a
      simpler application with the advantage that it can be applied in a more
      continuous way.

PMID- 22476879
TI  - Hepatocyte labeling with 99mTc-GSA: a potential non-invasive technique for
      tracking cell transplantation.
AB  - BACKGROUND: Hepatocyte transplantation is a promising alternative to orthotopic
      liver transplantation, however, the fate of transplanted hepatocytes is not well
      defined. 99mTc-galactosyl-serum albumin (99mTc-GSA) is a clinical scintigraphic
      agent which is specifically taken up by the hepatocyte asialoglycoprotein
      receptor (ASGPR). AIMS: To investigate labeling of fresh and cryopreserved human
      hepatocytes and fresh rat hepatocytes in vitro using 99mTc-GSA. METHODS: Human
      and rat hepatocytes were isolated from liver tissue by collagenase perfusion. The
      ASGPR were characterized using immunohistochemistry and RT-PCR. Hepatocytes were
      incubated with 99mTc-GSA in suspension at 4 degrees C and 37 degrees C. Cell
      viability and function was determined using cell mitochondrial dehydrogenase
      (MTS) and sulphorhodamine B (SRB) assays. RESULTS: Fresh and cryopreserved human
      hepatocytes expressed the ASGPR. Incubation of hepatocytes in suspension with
      99mTc-GSA reduced the viability of hepatocytes, but this was similar to unlabeled
      control cells. Greater loss of viability was seen on incubation at 37 degrees C
      compared to 4 degrees C, but there was a significantly greater uptake of 99mTc
      GSA at the physiological temperature (6.6 +/- SE 0.6-fold increase, p<0.05)
      consistent with ASGPR-mediated endocytosis. MTS and SRB assays were not
      significantly affected by labeling with 99mTc-GSA in all three cell types. A mean
      of 18.5% of the radioactivity was released over 120 min when 99mTc-GSA -labeled
      hepatocytes were shaken in vitro at 37 degrees C. CONCLUSIONS: Human and rat
      hepatocytes can be labeled with 99mTc-GSA, which may have potential application
      for in vivo imaging after hepatocyte transplantation.

PMID- 22476880
TI  - Delusional parasitosis: a rare cause of pruritus in hemodialysis patients.
AB  - Uremic pruritus is a common symptom in patients undergoing hemodialysis (HD) or
      peritoneal dialysis, but its exact pathogenesis remains rather unclear. However,
      severe or "intractable" pruritus may be the manifestation of another underlying
      disease or disorder other than uremia.  Delusional parasitosis, or Ekbom
      syndrome, is a rare psychiatric disorder characterized by the false conviction of
      being infested with parasites, and it can be primary, or secondary to several
      medical and psychiatric disorders. We report 2 elderly HD patients who presented
      one after another, with delusional parasitosis. At some point in time, the
      delusional beliefs of the first patient were adopted by the second patient who
      was waiting to start his HD session on the same bed and HD machine, on a
      subsequent shift. They were both diagnosed with Ekbom syndrome and described as
      having monosymptomatic hypochondriac delusion. They were both prescribed
      antipsychotic medications. During follow-up they admitted feeling better than
      before; however, they remained concerned about the "insects/parasites."

PMID- 22476881
TI  - Treatment of medically refractory hypercalcemic crisis.
AB  - INTRODUCTION: A 58-year-old patient was admitted to the intensive care unit for
      severe hypercalcemia (total Ca 5.30 mmol/L) complicated with status epilepticus,
      hypertensive crisis and acute renal failure. Renal replacement therapy was
      explored as a method for treating medically refractory hypercalcemia. METHODS:
      Because of hemodynamic instability during intermittent hemodialysis (IHD),
      continuous venovenous hemofiltration (CVVH) with high rates of calcium-free
      replacement fluids was instituted. Epoprostenol rather than citrate was used as
      anticoagulation to ensure adequate extracorporeal anticoagulation. RESULTS: CVVH
      was continued for 40 hours total during which ionized calcium decreased from 2.19
      to 1.07 mmol/L. The etiology of the hypercalcemia was from autoinfarction of a
      parathyroid adenoma. CONCLUSIONS: This is the first case of hypercalcemia treated
      with CVVH with epoprostenol anticoagulation. This method avoids some of the
      pitfalls of using intermittent hemodialysis. It is also a rare example of
      hypercalcemia induced posterior reversible encephalopathy syndrome (PRES).

PMID- 22476882
TI  - Blood oxygenation using microbubble suspensions.
AB  - Microbubbles have been used in a variety of fields and have unique properties,
      for example shrinking collapse, long lifetime, efficient gas solubility, a
      negatively charged surface, and the ability to produce free radicals. In
      medicine, microbubbles have been used mainly as diagnostic aids to scan various
      organs of the body, and they have recently been investigated for use in drug and
      gene delivery. However, there have been no reports of blood oxygenation by use of
      oxygen microbubble fluids without shell reagents. In this study, we demonstrated
      that nano or microbubbles can achieve oxygen supersaturation of fluids, and may
      be sufficiently small and safe for infusion into blood vessels. Although Po(2)
      increases in fluids resulting from use of microbubbles were inhibited by polar
      solvents, normal saline solution (NSS) was little affected. Thus, NSS is suitable
      for production of oxygen-rich fluid. In addition, oxygen microbubble NSS
      effectively improved hypoxic conditions in blood. Thus, use of oxygen microbubble
      (nanobubble) fluids is a potentially effective novel method for oxygenation of
      hypoxic tissues, for infection control, and for anticancer treatment.

PMID- 22476883
TI  - Incidence and treatment strategy for disseminated adenovirus disease after
      haploidentical stem cell transplantation.
AB  - Adenovirus (AdV) infection is an emerging complication in patients undergoing
      allogeneic stem cell transplantation (SCT) and is closely associated with delayed
      immune reconstitution. In particular, disseminated AdV disease accompanies a high
      mortality. We retrospectively examined the incidence of AdV infection in patients
      undergoing unmanipulated haploidentical SCT. Following 121 transplantations in
      110 patients, three had asymptomatic AdV viremia, three had localized AdV disease
      (hemorrhagic cystitis, HC), and seven had disseminated AdV disease (HC +
      viremia). The median time from transplantation to the onset of AdV-associated HC
      was 15 days (range 4-39), and the median time to the onset of disseminated AdV
      disease was 23 days (range 7-38). The cumulative incidence of AdV-associated HC
      was 8.3 %, and that of disseminated AdV disease was 5.8 %. AdV group B (type 11,
      type 34, or type 35) was detected in plasma samples from all the patients with
      disseminated AdV disease. Among them, three patients who received either
      cidofovir or donor lymphocyte infusion (DLI) alone progressed to pneumonia and
      died. The remaining four patients were treated with the combination of cidofovir
      and low-dose unmanipulated DLI, and all survived. We showed that disseminated AdV
      disease is a significant complication after haplo-SCT and that the combination of
      cidofovir and DLI is a promising treatment option.

PMID- 22476884
TI  - SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide,
      bortezomib, and lenalidomide) in the treatment of multiple myeloma.
AB  - In this project, we produced drug-specific recommendations targeting the use of
      new agents for multiple myeloma (MM). We used the GRADE (Grades of
      Recommendation, Assessment, Development, and Evaluation) system which separates
      the judgments on quality of evidence from the judgment about strength of
      recommendations. We recommended thalidomide and bortezomib in MM patients
      candidates to autologous stem cell transplantation (ASCT) (weak positive). We did
      not recommend novel agents as maintenance therapy after ASCT (weak negative). In
      patients not candidate to ASCT, thalidomide or bortezomib (strong positive)
      associated with melphalan and prednisone were recommended. In these patients, no
      specific course of action could be recommended as for maintenance therapy. In
      patients who are refractory or relapsing after first-line therapy, we recommended
      bortezomib and pegylated liposomal doxorubicin, or lenalidomide and dexamethasone
      combinations (weak positive).

PMID- 22476885
TI  - Transient appearance of GPI-deficient population in a patient with azathioprine
      associated bone marrow aplasia.

PMID- 22476886
TI  - Telomere elongation and clinical response to androgen treatment in a patient with
      aplastic anemia and a heterozygous hTERT gene mutation.
AB  - Telomere length (TL) both reflects and limits the replicative life span of normal
      somatic cells. As a consequence, critically shortened telomeres are associated
      with a variety of disease states. Telomere attrition can be counteracted by a
      nucleoprotein complex containing telomerase. Mutations in subunits of telomerase,
      telomerase-binding proteins as well as in members of the shelterin complex have
      been described both in inherited and acquired bone marrow failure syndromes.
      Here, we report on a patient with acquired aplastic anemia and a nonsynonymous
      variation of codon 1062 of the hTERT gene (p.Ala1062Thr) whose substantial and
      maintained hematologic response to long-term androgen treatment (including
      complete transfusion independence) was paralleled by a significant and continued
      increase in TL in multilineage peripheral blood cells. To our knowledge, this
      represents the first case of sustained telomere elongation in hematopoietic stem
      cells induced by a pharmacological approach in vivo (141 words).

PMID- 22476887
TI  - Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the liver: clinical,
      molecular, and microbiological aspects.

PMID- 22476888
TI  - Epitaxial crystal growth and solid-state polymerization of piperonyl muconate on
      the {001} surface of KCl crystal for controlling polymer chain alignment.
AB  - We investigated the crystal growth of piperonyl (E,E)-muconate [bis(3,4
      methylenedioxybenzyl) (E,E)-muconate, MDO] on inorganic crystalline substrates
      during vapor deposition for the control of polymer chain alignment by the
      subsequent solid-state photopolymerization of the MDO monomer thin films
      deposited on the substrate. We controlled the arrangement of the MDO molecules
      and the polymer chains produced on the substrate, depending on the lattice
      parameters of the substrate surfaces used. The epitaxial crystal growth of MDO on
      the {001} plane of a KCl single crystal was observed under the condition that the
      crystal lattice lengths of MDO agreed well with the specific space distance of
      the substrate; i.e., the KCl cubic crystal resulted in a d(110) value of 4.45 A,
      which was very close to the value of the monomer stacking distance in the MDO
      crystal (d(s) = 4.43 A). On the other hand, slightly large and too small d(110)
      values for KBr and NaCl, respectively, resulted in the less controlled and no
      epitaxial crystal growth of MDO. The irradiation of polarized UV light on the MDO
      thin-film crystal produced highly regulated polymer alignment in a specific
      direction on the KCl substrate.

PMID- 22476889
TI  - Surface acoustic wave nebulization produces ions with lower internal energy than
      electrospray ionization.
AB  - Surface acoustic wave nebulization (SAWN) has recently been reported as a novel
      method to transfer non-volatile analytes directly from solution to the gas phase
      for mass spectrometric analysis. Here we present a comparison of the survival
      yield of SAWN versus electrospray ionization (ESI) produced ions. A series of
      substituted benzylpyridinium (BzPy) compounds were utilized to measure ion
      survival yield from which ion energetics were inferred. We also estimated bond
      dissociation energies using higher level quantum chemical calculations than
      previously reported for BzPy ions. Additionally, the effects on BzPy precursor
      ion survival of SAWN operational parameters such as inlet capillary temperature
      and solution flow-rate were investigated. Under all conditions tested, SAWN
      generated BzPy ions displayed a higher tendency for survival and thus have lower
      internal energies than those formed by ESI.

PMID- 22476890
TI  - How ubiquitin unfolds after transfer into the gas phase.
AB  - The structural evolution of ubiquitin after transfer into the gas phase was
      studied by electron capture dissociation. Site-specific fragment yields show that
      ubiquitin's solution fold is overall unstable in the gas phase, but unfolding
      caused by loss of solvent is slowest in regions stabilized by salt bridges.

PMID- 22476892
TI  - The role of FDG PET-CT in the therapeutic evaluation for HNSCC patients.
AB  - F-18 FDG PET/CT has been widely used to diagnose primary tumors and lymph node
      metastases and to evaluate the response of head and neck squamous cell carcinoma
      (HNSCC) to therapy. The advantage of using PET/CT is that this combination allows
      metabolic information to be precisely overlapped with anatomical information,
      thereby improving the identification of sites with an abnormal accumulation of F
      18 FDG. The role of FDG PET/CT in the therapeutic evaluation (such as in
      treatment planning, the therapeutic response, and the surveillance and
      examination of HNSCC patients) is discussed in this manuscript. When evaluating
      the post-treatment outcome via FDG PET/CT, it is important to exclude the post
      treatment inflammation-related increase in glucose metabolism in lymph nodes,
      salivary gland, muscles, and soft tissues. The influence of inflammation can be
      eliminated if PET/CT is performed after 12 weeks, by which time post-treatment
      inflammation subsides. Further, FDG PET/CT affords a high negative predictive
      value. Based on the results of an FDG PET/CT test, some invasive tests that are
      performed to detect recurrence can be omitted.

PMID- 22476891
TI  - Hydrogen exchange mass spectrometry: are we out of the quicksand?
AB  - Although the use of hydrogen exchange (HX) mass spectrometry (MS) to study
      proteins and protein conformation is now over 20 years old, the perception
      lingers that it still has "issues." Is this method, in fact, still in the
      quicksand with many remaining obstacles to overcome? We do not think so. This
      critical insight addresses the "issues" and explores several broad questions
      including, have the limitations of HX MS been surmounted and has HX MS achieved
      "indispensable" status in the pantheon of protein structural analysis tools.

PMID- 22476893
TI  - Kidney stone erosion by micro scale hydrodynamic cavitation and consequent kidney
      stone treatment.
AB  - The objective of this study is to reveal the potential of micro scale
      hydrodynamic bubbly cavitation for the use of kidney stone treatment.
      Hydrodynamically generated cavitating bubbles were targeted to the surfaces of 18
      kidney stone samples made of calcium oxalate, and their destructive effects were
      exploited in order to remove kidney stones in in vitro experiments. Phosphate
      buffered saline (PBS) solution was used as the working fluid under bubbly
      cavitating conditions in a 0.75 cm long micro probe of 147 MUm inner diameter at
      9790 kPa pressure. The surface of calcium oxalate type kidney stones were exposed
      to bubbly cavitation at room temperature for 5 to 30 min. The eroded kidney
      stones were visually analyzed with a high speed CCD camera and using SEM
      (scanning electron microscopy) techniques. The experiments showed that at a
      cavitation number of 0.017, hydrodynamic bubbly cavitation device could
      successfully erode stones with an erosion rate of 0.31 mg/min. It was also
      observed that the targeted application of the erosion with micro scale
      hydrodynamic cavitation may even cause the fracture of the kidney stones within a
      short time of 30 min. The proposed treatment method has proven to be an efficient
      instrument for destroying kidney stones.

PMID- 22476894
TI  - Multiscale models of cell signaling.
AB  - Computational models of signal transduction face challenges of scale below the
      resolution of a single cell. Here, we organize these challenges around three key
      interfaces for multiscale models of cell signaling: molecules to pathways,
      pathways to networks, and networks to outcomes. Each interface requires its own
      set of computational approaches and systems-level data, and no single approach or
      dataset can effectively bridge all three interfaces. This suggests that realistic
      "whole-cell" models of signaling will need to agglomerate different model types
      that span critical intracellular scales. Future multiscale models will be
      valuable for understanding the impact of signaling mutations or population
      variants that lead to cellular diseases such as cancer.

PMID- 22476895
TI  - Microvascular transport and tumor cell adhesion in the microcirculation.
AB  - One critical step in tumor metastasis is tumor cell adhesion to the endothelium
      forming the microvessel wall. Understanding this step may lead to new therapeutic
      concepts for tumor metastasis. Vascular endothelium forming the microvessel wall
      and the glycocalyx layer at its surface are the principal barriers to, and
      regulators of the material exchange between circulating blood and body tissues.
      The cleft between adjacent ECs (interendothelial cleft) is the principal pathway
      for water and solutes transport through the microvessel wall in health. It is
      also suggested to be the pathway for high molecular weight plasma proteins,
      leukocytes and tumor cells across microvessel walls in disease. Thus the first
      part of the review introduced the mathematical models for water and solutes
      transport through the interendothelial cleft. These models, combined with the
      experimental results from in vivo animal studies and electron microscopic
      observations, are used to evaluate the role of the endothelial surface
      glycocalyx, the junction strand geometry in the interendothelial cleft, and the
      surrounding extracellular matrix and tissue cells, as the determinants of
      microvascular transport. The second part of the review demonstrated how the
      microvascular permeability, hydrodynamic factors, microvascular geometry and cell
      adhesion molecules affect tumor cell adhesion in the microcirculation.

PMID- 22476896
TI  - Do dynamic cement-on-cement knee spacers provide better function and activity
      during two-stage exchange?
AB  - BACKGROUND: Implantation of an antibiotic bone cement spacer is used to treat
      infection of a TKA. Dynamic spacers fashioned with cement-on-cement articulating
      surfaces potentially facilitate patient mobility and reduce bone loss as compared
      with their static counterparts, while consisting of a biomaterial not
      traditionally used for load-bearing articulations. However, their direct impact
      on patient mobility and wear damage while implanted remains poorly understood.
      QUESTIONS/PURPOSES: We characterized patient activity, surface damage, and porous
      structure of dynamic cement-on-cement spacers. METHODS: We collected 22 dynamic
      and 14 static knee antibiotic cement spacers at revision surgeries at times
      ranging from 0.5 to 13 months from implantation. For these patients, we obtained
      demographic data and UCLA activity levels. We characterized surface damage using
      the Hood damage scoring method and used micro-CT analysis to observe the internal
      structure, cracking, and porosity of the cement. RESULTS: The average UCLA score
      was higher for patients with dynamic spacers than for patients with static
      spacers, with no differences in BMI or age. Burnishing was the only prevalent
      damage mode on all the bearing surfaces. Micro-CT analysis revealed the internal
      structure of the spacers was porous and highly inhomogeneous, including
      heterogeneous dispersion of radiopaque material and cavity defects. The average
      porosity was 8% (range, 1%-29%) and more than 1/2 of the spacers had pores
      greater than 1 mm in diameter. CONCLUSIONS: Our observations suggest dynamic,
      cement-on-cement spacers allow for increased patient activity without
      catastrophic failure. Despite the antibiotic loading and internal structural
      inhomogeneity, burnishing was the only prevalent damage mode that could be
      consistently classified with no evidence of fracture or delamination. The porous
      structure of the spacers varied highly across the surfaces without influencing
      the material failure.

PMID- 22476897
TI  - Shoulder and elbow lesions distinctive of baseball players. 1947.

PMID- 22476898
TI  - Cell-based therapy improves function in adolescents and young adults with
      patellar osteochondritis dissecans.
AB  - BACKGROUND: Recent advances have been made in using chondrocytes and other cell
      based therapy to treat cartilage defects in adults. However, it is unclear
      whether these advances should be extended to the adolescent and young adult-aged
      patients. QUESTIONS/PURPOSES: We assessed cell-based surgical therapy for
      patellar osteochondritis dissecans (OCD) in adolescents and young adults by (1)
      determining function with the International Knee Documentation Committee (IKDC)
      subjective and Lysholm-Gillquist scores; and (2) evaluating activity level using
      the Tegner-Lysholm scale. METHODS: We retrospectively reviewed 23 patients
      between 12 and 21 years of age (mean 16.8 years) treated for OCD lesions
      involving the patella from 2001 to 2008. Twenty patients had autologous
      chondrocyte implantation and three patients had cultured bone marrow stem cell
      implantation. There were 19 males and four females. We obtained preoperative CT
      scans to assess patella subluxation, tilt, and congruence angle to determine
      choice of treatment. We obtained IKDC subjective knee evaluation scores, Tegner
      Lysholm activity levels, and Lysholm-Gillquist knee scores preoperatively and at
      6, 12, and 24 months postoperatively. RESULTS: Mean IKDC score, Tegner-Lysholm
      outcomes, and Lysholm-Gillquist scale improved from 45, 2.5, and 50,
      respectively, at surgery to 75, 4, and 70, respectively, at 24-month followup.
      Complications include periosteal hypertrophy observed in two patients.
      CONCLUSION: Cell-based therapy was associated with short-term improvement in
      function in adolescents and young adults with patellar OCD. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 22476899
TI  - Gene and protein expressions of vimentin and desmin during embryonic development
      of the mylohyoid muscle.
AB  - Meckel's cartilage is known to be involved in formation of the prenatal mandible.
      However, the relationship between Meckel's cartilage and the embryonic mylohyoid
      muscle during growth and development has been investigated only rarely. This
      study examined the expression of intermediate filaments in Meckel's cartilage and
      the embryonic mylohyoid muscle in fetal mice during morphological development.
      Specimens of E12-16 ICR mice sectioned in the frontal direction were subjected to
      immunohistochemistry for vimentin and desmin. Hematoxylin and eosin sections
      showed that the immature mylohyoid muscle began to grow along Meckel's cartilage
      during fetal development. Weak vimentin expression was detected in the mylohyoid
      muscle and surrounding tissues at E12. Desmin expression was detected
      specifically in the mylohyoid, and strong expression was evident after E13, and
      increased with age. It was inferred that the mylohyoid muscle is one the tissues
      developing from Meckel's cartilage, the latter exerting a continuous influence on
      the growth of the former. In the early stage, the surrounding mesenchymal tissues
      expressing vimentin formed a scaffold for the developing mylohyoid muscle. Muscle
      attachment at E13 showed steady desmin expression, which continued until
      maturity. This study suggested the possibility that Meckel's cartilage has an
      influence not only on the mandibular bone, but also on the development of the
      mylohyoid muscle attached to the mandibular bone. Furthermore, it revealed a
      stage of the developmental process of the mylohyoid muscle in which the
      expression of vimentin, which is a common protein in the surrounding tissue such
      as muscle and bone, induces the morphological formation of the mylohyoid muscle,
      cooperating with the surrounding structures.

PMID- 22476900
TI  - Nucleotide sequence of a chickpea chlorotic stunt virus relative that infects pea
      and faba bean in China.
AB  - We determined the genome sequence of a new polerovirus that infects field pea and
      faba bean in China. Its entire nucleotide sequence (6021 nt) was most closely
      related (83.3% identity) to that of an Ethiopian isolate of chickpea chlorotic
      stunt virus (CpCSV-Eth). With the exception of the coat protein (encoded by
      ORF3), amino acid sequence identities of all gene products of this virus to those
      of CpCSV-Eth and other poleroviruses were <90%. This suggests that it is a new
      member of the genus Polerovirus, and the name pea mild chlorosis virus is
      proposed.

PMID- 22476901
TI  - The enhanced antiproliferative response to combined treatment of trichostatin A
      with raloxifene in MCF-7 breast cancer cells and its relevance to estrogen
      receptor beta expression.
AB  - Antiestrogen is one type of the endocrine therapeutic agents for estrogen
      receptor alpha (ERalpha)-positive breast cancer. Unfortunately, this treatment
      alone is insufficient. Here we reported a novel potential anticancer strategy by
      using histone deacetylase (HDAC) inhibitor to enhance the action of endocrine
      therapy in ERalpha-positive breast cancer cell. The well-described HDAC
      inhibitor, trichostatin A (TSA), and antiestrogen raloxifene were found to,
      respectively, inhibit E2-induced proliferation of MCF-7 breast cancer cell in a
      dose-responsive and time-dependent manner. TSA and raloxifene enhanced the
      antiproliferative activity of each other by promoting cell death via apoptosis
      and cell cycle arrest. Thus, they displayed better antiproliferative effects in
      combined treatment than that with either agent alone. The expression level of
      estrogen receptor beta (ERbeta) showed a marked increase after TSA or/and
      raloxifene treatment. Treatments with TSA or/and raloxifene resulting in the up
      regulation of ERbeta are in accordance with the antiproliferative effects of the
      two agents. Furthermore, the over-expression of ERbeta by adenovirus delivery
      could inhibit the proliferation of MCF-7 tumor cells and drastically enhanced the
      antiproliferative effects of TSA and raloxifene. These results demonstrated that
      the interference of ERbeta on the antiproliferative effects of HDAC inhibitor and
      antiestrogen constitutes a promising approach for breast cancer treatment.

PMID- 22476902
TI  - Cellular mechanism underlying the facilitation of contractile response of vas
      deferens smooth muscle by sodium orthovanadate.
AB  - In the earlier study, sodium orthovanadate (SOV) has been reported to be a
      powerful inhibitor of (Na(+), K(+)) adenosine triphosphatase, exhibit widespread
      actions on the renal and cardiovascular systems, induces smooth muscle
      contraction by inhibiting the phosphorylation of the protein tyrosine
      phosphatases. In the current study, we aimed to investigate the cellular
      mechanisms by which SOV facilitated contractile response of vas deferens smooth
      muscle and its potential therapeutic advantage. Exogenous application of ATP and
      NA-caused contraction was strengthened by pretreatment with SOV. This
      facilitation was inhibited not by bath with the inhibitor of P2 receptor, PPADS,
      or the inhibitor of alpha1 receptor, Prazosin, but by bath with the protein
      tyrosine kinase inhibitor, Genistein. SOV induced a sustained increase in
      intracellular Ca(2+) of smooth muscle cells, which was abolished by 100 MUM
      Genistein or Ca(2+)-free solution. The facilitation of SOV could also be
      inhibited by the selective inhibitors of TRP channel, 2-APB and non-selective
      cation channel, Gd(3+), Ni(+). The in vivo study showed that peritoneal injection
      of SOV in dystrophic mice (mdx mice) enhanced the contraction of vas deferens
      smooth muscle stimulated by electrical field stimulation, ATP, noradrenaline, or
      KCl. The above results suggest that SOV facilitates the concentration of vas
      deferens smooth muscle through the tyrosine phosphorylation activated the non
      selective cation channels, which has potential use in the therapy for muscle
      dysfunction.

PMID- 22476904
TI  - Sin3 interacts with Foxk1 and regulates myogenic progenitors.
AB  - We have previously reported Foxk1 as an important transcription factor in the
      myogenic progenitors. SWI-independent-3 (Sin3) has been identified as a Foxk1
      binding candidate using a yeast two-hybrid screen. In the present study, we have
      identified the Foxk1 N-terminal (1-40) region as the Sin3 interacting domain
      (SID), and the PAH2 of Sin3 as the Foxk1 binding domain utilizing yeast two
      hybrid and GST pull-down assays. Further studies revealed that knockdown of Sin3a
      or Sin3b results in cell cycle arrest and upregulation of cell cycle inhibitor
      genes. In summary, our present studies have shown that Foxk1 interacts with Sin3
      through the SID and that Sin3 has an important role in the regulation of cell
      cycle kinetics of the MPC population. The results of these studies continue to
      define and assemble the networks that regulate the MPCs and muscle regeneration.

PMID- 22476903
TI  - Nutritional factors and bone homeostasis: synergistic effect with zinc and
      genistein in osteogenesis.
AB  - Bone homeostasis is regulated through osteoclasts and osteoblasts. Osteoporosis,
      which is induced with its accompanying decrease in bone mass with increasing age,
      is widely recognized as a major public health problem. Bone loss may be due to
      decreased osteoblastic bone formation and increased osteoclastic bone resorption.
      There is growing evidence that nutritional and food factors may play a part in
      the prevention of bone loss with aging and have been to be worthy of notice in
      the prevention of osteoporosis. Zinc, an essential trace element, or genistein,
      which are contained in soybeans, has been shown to have a stimulatory effect on
      osteoblastic bone formation and an inhibitory effect on osteoclastic bone
      resorption, thereby increasing bone mass. These factors have an effect on protein
      synthesis and gene expression, which are related to bone formation in
      osteoblastic cells and bone resorption in osteoclastic cells. The combination of
      zinc and genistein is found to reveal the synergistic effect on bone anabolic
      effect. The oral administration of those factors has been shown to prevent on
      bone loss in ovariectomized rats, an animal model for osteoporosis, indicating a
      role in the prevention of osteoporosis. Supplemental intake of ingredient with
      the combination of zinc and genistein has been shown to have a preventive effect
      on osteoporosis in human subjects, suggesting a role in the prevention of bone
      loss.

PMID- 22476905
TI  - Genome sequence determination and analysis of a Chinese virulent strain, LMS, of
      Gallid herpesvirus type 2.
AB  - Marek's disease (MD) is a neoplastic and neurodegenerative disease of chickens,
      which is caused by the Gallid herpesvirus type 2 (GaHV-2). Although vaccination
      has been used widely in China, MD still occurs frequently. Some molecular
      epidemiologic studies have shown that Chinese GaHV-2 isolates seem to constitute
      a separate clade from strains isolated from other regions. However, more of a
      genomic background of the Chinese strains is necessary. In 2007, a virulent GaHV
      2 field strain, named LMS, was isolated from diseased chicken flocks in the
      southwest of China. The whole genome sequence of LMS was determined to evaluate
      its genetic property. The genome of LMS is 177,526 bp long, and 197 open reading
      frames (ORFs) were predicted. Most of the ORFs have high sequence identity with
      homologous ORFs of reference strains. Two regions in the LMS genome are grossly
      different from other strains: the alpha-like region and the latency-associated
      transcripts (LATs) promoters. Evolutionary analysis demonstrated that LMS has a
      larger phylogenetic distance from most American isolated strains but a closer
      relationship with 648Ap80 and the European pC12/130 strain. The characterised
      genome of LMS provides further insight into the genetics of the Chinese GaHV-2
      field strains, which is useful for the control of MD in China.

PMID- 22476906
TI  - Phylogenetic analysis of hemagglutinin genes of 40 H9N2 subtype avian influenza
      viruses isolated from poultry in China from 2010 to 2011.
AB  - Avian influenza virus (H9N2) infection is a major problem of product performance
      in poultry worldwide. Vaccination is used to limit spread, but more knowledge is
      needed on the epidemiology of virus subtypes to improve vaccine design. In this
      study, 40 H9N2 subtype avian influenza viruses (AIVs) were isolated from
      vaccinated poultry flocks in China from 2010 to 2011. Hemagglutinin (HA) from
      different virus strains was sequenced and analyzed. We found that the HA genes of
      these strains shared nucleotide and deduced amino acid homologies that ranged
      from 90.1 to 92.9 and 91.4 to 95.0 %, respectively, when compared with vaccine
      strains. Phylogenetic analysis showed that the strains tested could be divided
      into two major groups. Group I consisted of 24 strains isolated mainly from
      Eastern and Central China. Group II consisted of 20 strains isolated from
      Southern China. The cleavage site within the HA protein contained two basic
      motifs, PSRSSR?GLF for group I, and PARSSR?GLF for group II. Additional potential
      glycosylation sites were found at amino acid position 295 in the HA1 of the
      isolates in group I, compared with isolates in group II and the vaccine strains.
      Furthermore, 38 out of the 40 isolates had a leucine residue at position 216 (aa
      226 in H3), which was characteristic of human influenza virus-like receptor
      specificity. In the present study we found that geographical factors play a
      significant role in virus evolution, and emphasize the importance of continuing
      surveillance of H9N2 AIVs in chickens in China.

PMID- 22476907
TI  - Temporal differences in ejection between right and left ventricles in chronic
      pulmonary hypertension: a pulsed Doppler study.
AB  - Chronic pulmonary hypertension (cPH) is known to alter right ventricular (RV)
      deformation and cause mechanical dyssynchrony. Since not all echocardiographic
      laboratories are equipped with sophisticated imaging tools, we decided to
      determine if Doppler would be useful to detect temporal differences between the
      ejection of the right and left ventricle (LV) as a result of cPH using pulsed
      outflow tract (RVOT and LVOT) spectral signals. Data was collected from 30
      patients without PH (Group I: 53 +/- 7 years and 31 +/- 5 mmHg) and from 40
      patients with cPH (Group II: 53 +/- 13 years; P = NS and 82 +/- 24 mmHg; P <
      0.00001). Group II patients had a longer temporal delay from onset between RVOT
      and LVOT (23 +/- 12 ms vs. 0 +/- 0 ms; P < 0.0001) with a significantly shorter
      temporal difference between RVOT and LVOT spectral signals to reach maximum peak
      of ejection (27 +/- 24 ms vs. 61 +/- 23 ms; P < 0.0001) than Group I. In
      addition, Group II had a statistically lower RVOT VTI value (0.14 +/- 0.05 cm vs.
      0.17 +/- 0.03 cm; P < 0.01). Our data seems to suggest that increasing severity
      of PH mainly affects ejection of the RV resulting in noticeable temporal
      alterations in both time of onset as well as time to reach maximum peak ejection
      between RV and LV. More studies are now required to determine the utility of
      obtaining these measurements prospectively in the follow-up and treatment of cPH
      patients.

PMID- 22476908
TI  - Quantification of myocardial perfusion reserve at 1.5 and 3.0 Tesla: a comparison
      to fractional flow reserve.
AB  - The objective of this study was to compare quantitative analysis of cardiac
      magnetic resonance (CMR) perfusion at 1.5 and 3 T against fractional flow reserve
      (FFR) as measured invasively. FFR is considered by many investigators to be a
      reliable standard to determine hemodynamically significant coronary artery
      stenoses. Quantitative 1.5 and 3 T CMR is capable to noninvasively determine
      myocardial perfusion reserve, but have not been compared against each other and
      validated against FFR as standard reference. Patients with suspected or known
      coronary artery disease (CAD) underwent CMR at at both field strengths, 1.5 and 3
      T, and FFR. 34 patients were included into the study. Quantitative myocardial
      perfusion reserve was calculated in 544 myocardial segments at 1.5 and 3 T,
      respectively. FFR was measured in 109 coronary arteries. FFR <= 0.8 was regarded
      relevant. Reduced FFR (<=0.8) was found in 38 coronary arteries (19 LAD, 8 LCX
      and 11 RCA). Receiver operator curve analysis yielded higher area under the curve
      for 3 T CMR in comparison to 1.5 T CMR (0.963 vs. 0.645, p < 0.001) resulting in
      higher sensitivity (90.5 vs. 61.9 %) and specificity (100 vs. 76.9 %).
      Quantitative analysis of CMR myocardial perfusion reserve at 1.5 and 3 T is
      capable to detect hemodynamic significance of coronary artery stenoses.
      Diagnostic accuracy at 3 T is to be superior to 1.5 T.

PMID- 22476909
TI  - Cardiovascular imaging 2011 in the International Journal of Cardiovascular
      Imaging.

PMID- 22476910
TI  - Artifact reduction strategies for prosthetic heart valve CT imaging.
AB  - Multislice CT evaluation of prosthetic heart valves (PHV) is limited by PHV
      related artifacts. We assessed the influence of different kV settings, a metal
      artifact reduction filter (MARF) and an iterative reconstruction algorithm (IR)
      on PHV-induced artifacts in an in vitro model. A Medtronic-Hall tilting disc and
      St Jude bileafet PHV were imaged using a 64-slice scanner with 100 kV/165 mAs,
      120 kV/100 mAs, 140 kV/67 mAs at an equal CTDI(vol). Images were reconstructed
      with (1) filtered back projection (FBP), (2) IR, (3) MARF and (4) MARF and IR.
      Hypo- and hyperdense artifacts volumes (mean mm(3) +/- SD) were quantified with 2
      thresholds (<=-50 and >=175 Hounsfield Units). Image noise was measured and the
      presence of secondary artifacts was scored by 2 observers independently. Mean
      hypodense artifacts for the Medtronic-Hall/St Jude valve (FBP) were 966 +/-
      23/1,738 +/- 21 at 100 kV, 610 +/- 13/991 +/- 12 at 120 kV, and 420 +/- 9/634 +/-
      9 at 140 kV. Compared to FBP, hypodense artifact reductions for IR were 9/8 %,
      10/7 % and 12/6 % respectively, for MARF 92 %/84 %, 89/81 % and 86/77 %
      respectively; for MARF + IR 94/85 %, 92/82 %, and 90/79 % respectively. Mean
      hyperdense artifacts for the Medtronic-Hall/St Jude valve were 5,530 +/- 48/6,940
      +/- 70 at 100 kV, 5,120 +/- 42/6,250 +/- 53 at 120 kV, and 5,011 +/- 52/6,000 +/-
      0 at 140 kV. Reductions for IR were 2/2 %, 2/3 % and 3/4 % respectively, for MARF
      were 9/30 %, 0/25 %, 5/22 % respectively, MARF + IR 12/32 %, 4/27 % and 7/25 %
      respectively. Secondary artifacts were found in all MARF images. Image noise was
      reduced in the IR images. In vitro PHV-related artifacts can be reduced by
      increasing kV despite maintaining identical CTDI(vol). Although MARF is more
      effective than IR, it induces secondary artifacts.

PMID- 22476911
TI  - Additional diverse findings expand the clinical presentation of DOCK8 deficiency.
AB  - We describe seven Turkish children with DOCK8 deficiency who have not been
      previously reported. Three patients presented with typical features of recurrent
      or severe cutaneous viral infections, atopic dermatitis, and recurrent
      respiratory or gastrointestinal tract infections. However, four patients
      presented with other features. Patient 1-1 featured sclerosing cholangitis and
      colitis; patient 2-1, granulomatous soft tissue lesion and central nervous system
      involvement, with primary central nervous system lymphoma found on follow-up;
      patient 3-1, a fatal metastatic leiomyosarcoma; and patient 4-2 showed no other
      symptoms initially besides atopic dermatitis. Similar to other previously
      reported Turkish patients, but in contrast to patients of non-Turkish ethnicity,
      the patients' lymphopenia was primarily restricted to CD4(+) T cells. Patients
      had homozygous mutations in DOCK8 that altered splicing, introduced premature
      terminations, destabilized protein, or involved large deletions within the gene.
      Genotyping of remaining family members showed that DOCK8 deficiency is a fully
      penetrant, autosomal recessive disease. In our patients, bone marrow
      transplantation resulted in rapid improvement followed by disappearance of viral
      skin lesions, including lesions resembling epidermodysplasia verruciformis,
      atopic dermatitis, and recurrent infections. Particularly for patients who
      feature unusual clinical manifestations, immunological testing, in conjunction
      with genetic testing, can prove invaluable in diagnosing DOCK8 deficiency and
      providing potentially curative treatment.

PMID- 22476912
TI  - Therapy with TLR7 agonists induces lymphopenia: correlating pharmacology to
      mechanism in a mouse model.
AB  - BACKGROUND AND OBJECTIVE: Synthetic TLR7 agonists have been proposed as oral
      replacements for interferonalpha (IFNalpha) therapy in the treatment of hepatitis
      C virus infection. However, adverse effects, such as lymphopenia and
      cardiovascular irregularities, have been observed in the clinical following
      treatment with TLR7 agonists. We wished to understand and characterise the
      relationship between TLR7 agonism and adverse effects. METHODS: We compared
      responses to two prototypic TLR7 agonists (Resiquimod: R-848; and PF-04878691) in
      a mouse model and compared the responses to treatment with IFNalpha. We measured
      clinically relevant adverse effects such as lymphopenia and cardiovascular
      irregularities and related them to plasma drug levels and clinically relevant
      efficacy biomarkers such as the pro-inflammatory cytokine IP-10, 2'5'OAS and TLR7
      receptor expression. RESULTS: By 2 h post dose all agents had induced a dose
      dependent transient lymphopenia. IFNalpha increased heart rate immediately
      following dosing, persisting for 5 h, whilst PF-04878691 induced significant
      reductions in blood pressure. Lymphopenia co-incided with maximum plasma drug
      levels, raised levels of IP-10 and the auto-induction of TLR7 expression in the
      blood and lymph nodes. Peak levels of 2'5'OAS occurred at 24 h post-dose and only
      at doses which also induced lymphopenia. CONCLUSIONS: We conclude that systemic
      delivery of TLR7 agonists or IFNalpha induces similar exaggerated pharmacology,
      consistent with there being a narrow therapeutic window between efficacy and
      safety. This clinically validated mouse model will help to investigate whether
      more potent agonists or optimised dosing schedules, will be successful strategies
      for targeting TLR7 in patients.

PMID- 22476913
TI  - Ligand binding assays in the 21st century laboratory-a call for change.

PMID- 22476914
TI  - Atherosclerosis, inflammation, genetics, and stem cells: 2012 update.
AB  - Atherosclerosis is a peculiar form of inflammation triggered by cholesterol-rich
      lipoproteins and other noxious factors such as cigarette smoke, diabetes
      mellitus, and hypertension. Genetics also play an important role in the disease,
      accounting for about 40% of the risk. Of surprise in recent years of post-human
      genome sequencing, atherosclerosis-relevant genes discovered by non-biased
      techniques (ie, genome-wide association studies), did not rehash previously
      suspected pathways of lipid metabolism, diabetes, or hypertension. Instead these
      studies highlighted genes relevant to mechanisms of inflammation and stem cell
      biology. Only a minority of implicated genes were linked to lipid and other
      cardiac risk factor genes. Although such findings do not contradict the fact that
      atherosclerosis is triggered and exacerbated by elevated lipids, atherosclerosis
      "new genes" suggest that the mechanism responsible for the development of
      arterial lesions is more complex than a simple response to injury, where injury
      is necessary, but perhaps not sufficient, for disease progression.

PMID- 22476915
TI  - The effect of exercise on IL-6-induced cachexia in the Apc ( Min/+) mouse.
AB  - BACKGROUND: Cachexia involves unintentional body weight loss including diminished
      muscle and adipose tissue mass and is associated with an underlying disease.
      Systemic overexpression of IL-6 accelerates cachexia in the Apc(Min/+) mouse, but
      does not induce wasting in control C57BL/6 mice. With many chronic diseases,
      chronic inflammation and metabolic dysfunction can be improved with moderate
      exercise. A direct effect of regular moderate exercise on the prevention of IL-6
      induced cachexia in the Apc(Min/+) mouse has not been investigated. The purpose
      of this study was to assess the effects of exercise on the development of
      cachexia in the Apc(Min/+) mouse. METHODS: Mice were randomly assigned to
      moderate treadmill exercise (18 m/min, 1 h, 6 days/week, 5% grade) or cage
      control (CC) groups from 6 to 14 weeks of age. At 12 weeks of age, mice were
      electroporated with either IL-6-containing or control plasmid into the quadriceps
      muscle. Mice were killed after 2 weeks of systemic IL-6 overexpression or control
      treatment. RESULTS: IL-6 overexpression induced an 8% loss in body weight in CC
      mice, which was significantly attenuated by exercise. IL-6 overexpression in CC
      mice increased fasting insulin and triglyceride levels, which were normalized by
      exercise, and associated with increased oxidative capacity, an induction of AKT
      signaling, and a repression of AMPK signaling in muscle. These exercise-induced
      changes occurred despite elevated inflammatory signaling in skeletal muscle.
      CONCLUSION: We conclude that moderate-intensity exercise can attenuate IL-6
      dependent cachexia in Apc(Min/+) mice, independent of changes in IL-6
      concentration and muscle inflammatory signaling. The exercise effect was
      associated with improved insulin sensitivity and improved energy status in the
      muscle.

PMID- 22476918
TI  - Effect of sexual dimorphism on muscle strength in cachexia.
AB  - BACKGROUND: Reduced muscle strength is a cardinal feature in cachexia. We
      investigated whether weight loss is associated differently with muscle strength
      in men and women in a large cohort of hospitalized patients. METHODS: One
      thousand five hundred hospitalized patients (whereof 718 men, mean age 57.6 +/-
      16.0 years, mean body mass index (BMI) 24.6 +/- 4.8 kg/m2) were included in the
      study. Non-edematous involuntary weight loss was determined with Subjective
      Global Assessment; isometric maximal muscle strength was evaluated by hand grip
      strength. Mid-upper arm circumference and triceps skinfold were used to calculate
      arm muscle area. Interrelationship between sex and weight loss was evaluated by
      regression analysis performed with the general linear model (GLM) allowing
      adjustment for continuous and categorical variables and corrected for age, arm
      muscle area (AMA), BMI, and diagnosis category (benign/malignant disease) as
      potentially confounding covariates. RESULTS: Both men and women exhibited a
      significant stepwise decrease of hand grip strength with increasing weight loss.
      Age, sex, moderate and severe weight loss, BMI, and AMA were significant
      predictors of hand grip strength. The GLM moreover revealed a significant sex *
      weight loss effect, since grip strength was similarly decreased in moderate
      weight loss in men and women when compared to control patients without weight
      loss (8.5% in men and 10.5% in women, not significant (n.s.)), but the further
      reduction of grip strength in severe weight loss was significantly different
      between men and women (10.6% vs. 4.1%, P = 0.033). CONCLUSIONS: Our findings
      indicate sex-specific differences in muscle strength response to weight loss.

PMID- 22476919
TI  - Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse
      model of burn cachexia.
AB  - BACKGROUND: Burn injury results in a chronic inflammatory, hypermetabolic, and
      hypercatabolic state persisting long after initial injury and wound healing. Burn
      survivors experience a profound and prolonged loss of lean body mass, fat mass,
      and bone mineral density, associated with significant morbidity and reduced
      quality of life. Understanding the mechanisms responsible is essential for
      developing therapies. A complete characterization of the pathophysiology of burn
      cachexia in a reproducible mouse model was lacking. METHODS: Young adult (12-16
      weeks of age) male C57BL/6J mice were given full thickness burns using heated
      brass plates or sham injury. Food and water intake, organ and muscle weights, and
      muscle fiber diameters were measured. Body composition was determined by Piximus.
      Plasma analyte levels were determined by bead array assay. RESULTS: Survival and
      weight loss were dependent upon burn size. The body weight nadir in burned mice
      was 14 days, at which time we observed reductions in total body mass, lean
      carcass mass, individual muscle weights, and muscle fiber cross-sectional area.
      Muscle loss was associated with increased expression of the muscle ubiquitin
      ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral
      density, concomitant with increased liver, spleen, and heart mass. Recovery of
      initial body weight occurred at 35 days; however, burned mice exhibited
      hyperphagia and polydipsia out to 80 days. Burned mice had significant increases
      in serum cytokine, chemokine, and acute phase proteins, consistent with findings
      in human burn subjects. CONCLUSIONS: This study describes a mouse model that
      largely mimics human pathophysiology following severe burn injury. These baseline
      data provide a framework for mouse-based pharmacological and genetic
      investigation of burn-injury-associated cachexia.

PMID- 22476920
TI  - The sensitivity of sheep to vecuronium: an example of the limitations of
      extrapolation.

PMID- 22476916
TI  - Sarcopenia and cachexia: the adaptations of negative regulators of skeletal
      muscle mass.
AB  - Recent advances in our understanding of the biology of muscle, and how anabolic
      and catabolic stimuli interact to control muscle mass and function, have led to
      new interest in the pharmacological treatment of muscle wasting. Loss of muscle
      occurs as a consequence of several chronic diseases (cachexia) as well as normal
      aging (sarcopenia). Although many negative regulators [Atrogin-1, muscle ring
      finger-1, nuclear factor-kappaB (NF-kappaB), myostatin, etc.] have been proposed
      to enhance protein degradation during both sarcopenia and cachexia, the
      adaptation of mediators markedly differs among these conditions. Sarcopenic and
      cachectic muscles have been demonstrated to be abundant in myostatin- and
      apoptosis-linked molecules. The ubiquitin-proteasome system (UPS) is activated
      during many different types of cachexia (cancer cachexia, cardiac heart failure,
      chronic obstructive pulmonary disease), but not many mediators of the UPS change
      during sarcopenia. NF-kappaB signaling is activated in cachectic, but not in
      sarcopenic, muscle. Some studies have indicated a change of autophagic signaling
      during both sarcopenia and cachexia, but the adaptation remains to be elucidated.
      This review provides an overview of the adaptive changes in negative regulators
      of muscle mass in both sarcopenia and cachexia.

PMID- 22476917
TI  - Evolving concepts on the age-related changes in "muscle quality".
AB  - The deterioration of skeletal muscle with advancing age has long been anecdotally
      recognized and has been of scientific interest for more than 150 years. Over the
      past several decades, the scientific and medical communities have recognized that
      skeletal muscle dysfunction (e.g., muscle weakness, poor muscle coordination,
      etc.) is a debilitating and life-threatening condition in the elderly. For
      example, the age-associated loss of muscle strength is highly associated with
      both mortality and physical disability. It is well-accepted that voluntary muscle
      force production is not solely dependent upon muscle size, but rather results
      from a combination of neurologic and skeletal muscle factors, and that biologic
      properties of both of these systems are altered with aging. Accordingly, numerous
      scientists and clinicians have used the term "muscle quality" to describe the
      relationship between voluntary muscle strength and muscle size. In this review
      article, we discuss the age-associated changes in the neuromuscular system
      starting at the level of the brain and proceeding down to the subcellular level
      of individual muscle fibers-that are potentially influential in the etiology of
      dynapenia (age-related loss of muscle strength and power).

PMID- 22476921
TI  - Chronic kidney disease categories and renal-cardiovascular outcomes in type 2
      diabetes without prevalent cardiovascular disease: a prospective cohort study
      (JDDM25).
AB  - AIMS/HYPOTHESIS: In type 2 diabetic patients at low risk for cardiovascular
      disease (CVD), the relationship between the clinical course of nephropathy by
      stage of chronic kidney disease (CKD) and onset of CVD remains unclear.
      Clarification of this relationship is important for clinical decision-making for
      both low- and high-risk diabetic patients. METHODS: This 4 year prospective study
      enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum
      creatinine <176.8 MUmol/l. The risk for CVD onset (non-fatal and fatal CVD and
      stroke, and peripheral arterial disease) was assessed according to CKD stage
      categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated
      GFR (eGFR; ml min(-1) 1.73 m(-2)). Association of progression from 'no CKD' stage
      (ACR <3.5 mg/mmol and eGFR >= 90 ml min(-1) 1.73 m(-2)) with risk for CVD onset
      was also evaluated. RESULTS: During follow-up (median 3.8 years), 89 CVD events
      occurred. Compared with patients with 'no CKD' as reference, those with ACR >=
      35.0 mg/mmol with co-existing eGFR 60-89 ml min(-1) 1.73 m(-2) or <60 ml min(-1)
      1.73 m(-2) showed increased risk for CVD onset, whereas those with eGFR >= 90 ml
      min(-1) 1.73 m(-2) did not. Those with ACR <3.5 mg/mmol and eGFR <60 ml min(-1)
      1.73 m(-2) did not show any increased risk. Among patients with 'no CKD' stage at
      baseline, those who progressed to ACR >= 3.5 mg/mmol during follow-up showed an
      increased risk compared with those who did not, whereas those who progressed to
      eGFR <90 ml min(-1) 1.73 m(-2) did not have increased risk.
      CONCLUSIONS/INTERPRETATION: The risk for CVD was associated with progression of
      albuminuria stage rather than eGFR stage in type 2 diabetic patients at
      relatively low risk for CVD.

PMID- 22476922
TI  - Empathizing with a dissimilar other: the role of self-other distinction in
      sympathetic responding.
AB  - Can we empathize effectively with someone who has a different sensitivity to
      physical events from ours? Or, are we susceptible to an egocentric bias in
      overprojection, which may lead us to under- or overreact in such cases? In this
      study, participants with normal visual and auditory capacity observed a video
      clip in which a sighted or blind target was exposed to a strong flash or high
      frequency sound, while their physiological arousals during the observation were
      recorded. On average, participants displayed a differential arousal pattern to
      the aversive stimuli, according to the target's ability to perceive them. Degrees
      of arousal control were also correlated with dispositional differences in
      empathy. Participants who scored higher on the Empathic Concern subscale of
      Davis's Interpersonal Reactivity Index were better at controlling arousals in
      accordance with the Target * Stimulus interaction. The authors' findings have
      important implications for helping disabled people while respecting their
      inherent dignity and individual autonomy.

PMID- 22476923
TI  - Chronic cigarette smoke exposure enhances brain-derived neurotrophic factor
      expression in rats with traumatic brain injury.
AB  - The involvement of brain-derived neurotrophic factor (BDNF) in regulating
      neuronal survival during neuron differentiation, growth, and maturation, and
      during the regeneration of injured nerve cells, has already been documented. In
      experimental Parkinson's disease, chronic exposure to cigarette smoke increased
      BDNF levels and survival of dopaminergic neurons. BDNF is also elevated in
      traumatic brain injury (TBI), where it is potentially involved in post-injury
      repair and regeneration. The aim of this study was to investigate the effects of
      chronic exposure to cigarette smoke on BDNF expression and apoptosis in rats with
      TBI. Three groups of rats were compared: rats with TBI after chronic exposure to
      cigarette smoke, rats with TBI and no exposure to cigarette smoke, and sham
      operated rats. BDNF mRNA expression in the hippocampus increased from 2 to 24 h
      after TBI, and chronic exposure to cigarette smoke upregulated TBI-induced BDNF
      mRNA elevation at 0, 2, 4, 12, and 24 h after head injury. The BDNF protein
      levels generally corresponded to the mRNA levels in the hippocampal region.
      Compared to the TBI group without smoke exposure, chronic cigarette smoke
      exposure in rats inhibited the decrease of the Bcl-2/Bax ratio and reduced P53
      expression and apoptosis 24 h after TBI. In addition, neuronal damage in the
      parietal and cingulate cortex 7 days after TBI was less extensive in rats exposed
      to cigarette smoke. In conclusion, although chronic exposure to cigarette smoke
      is a risk factor for myocardial and pulmonary disease, cigarette smoke exposure
      increases BDNF expression after TBI and thereby can play a neuroprotective role.

PMID- 22476924
TI  - Maternal separation enhances object location memory and prevents exercise-induced
      MAPK/ERK signalling in adult Sprague-Dawley rats.
AB  - Early life stress increases the risk of developing psychopathology accompanied by
      reduced cognitive function in later life. Maternal separation induces anxiety
      like behaviours and is associated with impaired memory. On the other hand,
      exercise has been shown to diminish anxiety-like behaviours and improve cognitive
      function. The effects of maternal separation and exercise on anxiety, memory and
      hippocampal proteins were investigated in male Sprague-Dawley rats. Maternal
      separation produced anxiety-like behaviours which were reversed by exercise.
      Maternal separation also enhanced object location memory which was not affected
      by exercise. Exercise did, however, increase synaptophysin and phospho
      extracellular signal-regulated kinase (p-ERK) in the hippocampus of non-separated
      rats and this effect was not observed in maternally separated rats. These
      findings show that maternal separation selectively enhanced n memory and
      prevented activation of the MAPK/ERK signalling pathway in the adult rat
      hippocampus.

PMID- 22476925
TI  - Hexane fraction from Laminaria japonica exerts anti-inflammatory effects on
      lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting NF-kappaB
      pathway.
AB  - PURPOSE: Laminaria japonica is a representative marine brown alga used as a
      culinary item in East Asia. L. japonica extract was shown to exert various
      biological activities; however, its anti-inflammatory activity has not been
      reported. The aim of this study is to investigate the molecular mechanisms
      underlying its anti-inflammatory action. METHODS: Anti-inflammatory mechanisms of
      L. japonica n-hexane fraction (LHF) were assessed using lipopolysaccharide (LPS)
      stimulated RAW 264.7 macrophages. An anti-inflammatory compound isolated from LHF
      by reverse-phase chromatography was identified using nuclear magnetic resonance
      (NMR) spectroscopy. RESULTS: Our results indicate that LHF significantly
      inhibited LPS-stimulated nitric oxide (NO) and prostaglandin E(2) (PGE(2))
      secretion in a dose-dependent manner and suppressed the expression of inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) with no cytotoxicity.
      As results, levels of pro-inflammatory cytokines were significantly reduced by
      pretreatment of LHF in LPS-stimulated RAW 264.7 cells. Treatment of LHF strongly
      suppressed nuclear factor-kappaB (NF-kappaB) promoter-driven expression and
      nuclear translocation of NF-kappaB by preventing proteolytic degradation of
      inhibitor of kappaB (IkappaB)-alpha in LPS-stimulated RAW 264.7 cells. Moreover,
      LHF inhibited the phosphorylation of Akt and mitogen-activated protein kinase
      (MAPK) in LPS-stimulated RAW 264.7 cells. One of the anti-inflammatory compounds
      was isolated from LHF and identified as fucoxanthin. CONCLUSIONS: These results
      indicate that the LHF-mediated inhibition of NO and PGE(2) secretion in LPS
      stimulated macrophages is regulated by NF-kappaB inactivation through inhibition
      of IkappaB-alpha, MAPKs, and Akt phosphorylation. LHF may be considered as a
      functional food candidate for the prevention or treatment of inflammatory
      diseases.

PMID- 22476926
TI  - Effects of pre-exercise feeding on serum hormone concentrations and biomarkers of
      myostatin and ubiquitin proteasome pathway activity.
AB  - PURPOSE: The aim of the study was to examine the acute effects of pre-exercise
      ingestion of protein, carbohydrate, and a non-caloric placebo on serum
      concentrations of insulin and cortisol, and the intramuscular gene expression of
      myostatin- and ubiquitin proteasome pathway (UPP)-related genes following a bout
      of resistance exercise. METHODS: Ten untrained college-aged men participated in
      three resistance exercise sessions (3 * 10 at 80 % 1RM for bilateral hack squat,
      leg press, and leg extension) in a cross-over fashion, which were randomly
      preceded by protein, carbohydrate, or placebo ingestion 30 min prior to training.
      Pre-supplement/pre-exercise, 2 h and 6 h post-exercise muscle biopsies were
      obtained during each session and analyzed for mRNA fold changes in myostatin
      (MSTN), activin IIB, follistatin-like 3 (FSTL3), SMAD specific E3 ubiquitin
      protein ligase 1 (SMURF1), forkhead box O3, F-box protein 32 (FBXO32), and Muscle
      RING-finger protein-1, with beta-actin serving as the housekeeping gene. Gene
      expression of all genes was analyzed using real-time PCR. RESULTS: Acute feeding
      appeared to have no significant effect on myostatin or UPP biomarkers. However,
      resistance exercise resulted in a significant downregulation of MSTN and FBXO32
      mRNA expression and a significant upregulation in FSTL3 and SMURF1 mRNA
      expression (p < 0.05). CONCLUSIONS: An acute bout of resistance exercise results
      in acute post-exercise alterations in intramuscular mRNA expression of myostatin
      and UPP markers suggestive of skeletal muscle growth. However, carbohydrate and
      protein feeding surrounding resistance exercise appear to have little influence
      on the acute expression of these markers.

PMID- 22476927
TI  - Management of squamous cell cancer of the oesophagus in a patient with a
      polyglandular endocrinopathy (APECED) and achalasia.
AB  - INTRODUCTION: We report a case of a 37-year-old man, with a background of a rare
      polyglandular autoimmune syndrome and achalasia, who developed an oesophageal
      tumour. Both autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
      (APECED) or type I polyglandular syndrome and achalasia confer increased risk of
      development of oesophageal squamous cell carcinoma. METHODS: Despite having had
      multiple endoscopic examinations and dilatations in the recent past, this patient
      presented with dysphagia, and on endoscopy, he was found to have a mid
      oesophageal tumour. A multidisciplinary team approach was vital in his management
      as careful monitoring of underlying disorders including Addison's disease and
      hypoparathyroidism were challenging during neoadjuvant chemoradiotherapy and in
      the perioperative period. RESULTS: He made an uneventful recovery after a three
      stage oesophagectomy, and histologically, he had a complete pathological
      response. CONCLUSION: To our knowledge, this is the first successful outcome of a
      patient with APECED and oesophageal carcinoma in the literature.

PMID- 22476928
TI  - Blunt diaphragmatic rupture--a rare injury in blunt thoracoabdominal trauma.
AB  - INTRODUCTION: Blunt traumatic rupture of the diaphragm is rare. DISCUSSION: We
      provide a case report of rupture of the diaphragm with visceral herniation in
      blunt thoracoabdominal trauma.

PMID- 22476929
TI  - In vitro propagation of Dioscorea alata var. purpurae.
AB  - Dioscorea alata var. purpurae (Indian purple yam) is an important source of
      diosgenin, a triterpenoid that is used as a raw material in the synthesis of
      corticosteroid hormones. These drugs are used for the treatment of
      pharmacological conditions such as arthritis. This paper reports in vitro
      propagation of explants of various parts of Dioscorea-tuber, leaves, and nodes.
      Murashige and Skoog media supplemented with hormones and additives was used to
      get maximum callus initiation and shoot/root induction. All the cultures were
      maintained at 25 +/- 2  degrees C under cool-white fluorescent tubes with 16-h
      photoperiod. Callus initiation was observed from 8th to 11th day of inoculation,
      and subsequent root/shoot was initiated in nodal callus after 21 days. Hormones
      such as kinetin, indole-3-acetic acid, indole-3-butyric acid, alpha-naphthalene
      acetic acid, and thiadizuron did not show significant enhancement. Also, there
      was no need for supplementing additives (silver nitrate, glutamine, L-:
      asparagine monohydrate, polyethylene glycol). Combination of 6-benzylaminopurine
      (0.2 ppm) and 2,4-dichlorophenoxyacetic acid (2 ppm) hormones gave the best
      results, and all parts of the plants gave similar callus induction.

PMID- 22476930
TI  - Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression.
AB  - The semaphorins and plexins comprise a family of cysteine-rich proteins
      implicated in control of nerve growth and development and regulation of the
      immune response. Our group and others have found that Semaphorin 4D (SEMA4D) and
      its receptor, Plexin-B1, play an important role in tumor-induced angiogenesis,
      with some neoplasms producing SEMA4D in a manner analogous to vascular
      endothelial growth factor (VEGF) in order to attract Plexin-B1-expressing
      endothelial cells into the tumor for the purpose of promoting growth and
      vascularity. While anti-VEGF strategies have been the focus of most angiogenesis
      inhibition research, such treatment can lead to upregulation of pro-angiogenic
      factors that can compensate for the loss of VEGF, eventually leading to failure
      of therapy. Here, we demonstrate that SEMA4D cooperates with VEGF to promote
      angiogenesis in malignancies and can perform the same function in a setting of
      VEGF blockade. We also show the potential value of inhibiting SEMA4D/Plexin-B1
      signaling as a complementary mechanism to anti-VEGF treatment, particularly in
      VEGF inhibitor-resistant tumors, suggesting that this may represent a novel
      treatment for some cancers.

PMID- 22476931
TI  - Metal-on-metal bearings, inflammatory pseudotumours and their neurological
      manifestations.
AB  - Metal-on-metal bearings have become more popular for hip arthroplasty in younger
      patients in the last 15 years. We present a review of the neurological
      consequences relating to such bearing surfaces illustrated by an appropriate case
      report. The mechanisms of increased metal ion production and pseudotumour
      formation are discussed. If unexplained neurology, hip/groin pain or a localised
      mass around the hip are present with a metal bearing hip then urgent referral to
      a specialist orthopaedic surgeon is warranted for consideration of exchange
      arthroplasty.

PMID- 22476932
TI  - Debonding of the acetabular porous coating of a hip resurfacing arthroplasty: a
      case report.
AB  - We report an unusual case of loosening of the acetabular component of a hip
      resurfacing arthroplasty due to debonding of the titanium surface coating from
      the acetabular shell. A 41-year-old male scaffolder had bilateral hip
      resurfacings in 2006. These initially functioned well. At 54 months he was found
      to have migration of the acetabular component on the right side. This was
      subsequently revised to a cemented total hip arthroplasty. Debonding of the
      surface coating was suspected on radiographs prior to the revision procedure, and
      was confirmed intraoperatively.

PMID- 22476933
TI  - Indications for early hip revision surgery in the UK--a re-analysis of NJR data.
AB  - This study determined the rate and indication for revision between cemented,
      uncemented, hybrid and resurfacing groups from NJR (6th edition) data. Data
      validity was determined by interrogating for episodes of misclassification. We
      identified 6,034 (2.7%) misclassified episodes, containing 97(4.3%) revisions.
      Kaplan-Meier revision rates at 3 years were 0.9% cemented, 1.9% for
      uncemented,1.2% for hybrids and 3.0% for resurfacings (significant difference
      across all groups, p<0.001, with identical pattern in patients <55 years).
      Regression analysis indicated both prosthesis group and age significantly
      influenced failure (p<0.001). Revision for pain, aseptic loosening, and
      malalignment were highest in uncemented and resurfacing arthroplasty. Revision
      for dislocation was highest in uncemented hips (significant difference between
      groups, p<0.001). Feedback to the NJR on data misclassification has been made for
      future analysis.

PMID- 22476934
TI  - Oligomer formation pathways in secondary organic aerosol from MS and MS/MS
      measurements with high mass accuracy and resolving power.
AB  - Secondary organic aerosol (SOA) is formed when organic molecules react with
      oxidants in the gas phase to form particulate matter. Recent measurements have
      shown that more than half of the mass of laboratory-generated SOA consists of
      high molecular weight oligomeric compounds. In this work, the formation
      mechanisms of oligomers produced in the laboratory by ozonolysis of alpha-pinene,
      an important SOA precursor in ambient air, are studied by MS and MS/MS
      measurements with high accuracy and resolving power to characterize monomer
      building blocks and the reactions that couple them together. The distribution of
      oligomers in an SOA sample is complex, typically yielding over 1000 elemental
      formulas that can be assigned from an electrospray ionization mass spectrum.
      Despite this complexity, MS/MS spectra can be found that give strong evidence for
      specific oligomer formation pathways that have been postulated but not confirmed.
      These include aldol and gem-diol reactions of carbonyls as well as
      peroxyhemiacetal formation from hydroperoxides. The strongest evidence for
      carbonyl reactions is in the formation of hydrated products. Less compelling
      evidence is found for dehydrated products and secondary ozonide formation. The
      number of times that a monomer building block is observed as a fragmentation
      product in the MS/MS spectra is shown to be independent of the monomer vapor
      pressure, suggesting that oligomer formation is not driven by equilibrium
      partitioning of a monomer between the gas and particle phases, but rather by
      reactive uptake where a monomer collides with the particle surface and rapidly
      forms an oligomer.

PMID- 22476936
TI  - Inhibitory effects of Ginkgo biloba extract on inflammatory mediator production
      by Porphyromonas gingivalis lipopolysaccharide in murine macrophages via Nrf-2
      mediated heme oxygenase-1 signaling pathways.
AB  - Periodontitis is an oral chronic inflammatory disease that influences systemic
      diseases. Heme oxygenase-1 has several beneficial abilities through Nrf-2
      regulation. Ginkgo biloba has been reported to have anti-inflammatory effects
      associated with heme oxygenase-1 (HO-1) expression. In this study, we
      investigated whether the anti-inflammatory effects of G. biloba were involved
      with Nrf-2-mediated HO-1 expression in Porphyromonas gingivalis LPS-stimulated
      RAW264.7 macrophage cells. G. biloba was extracted with ethyl acetate (EGB). EGB
      exhibited anti-inflammatory activities, which suppressed the production of pro
      inflammatory mediators, the activation of mitogen-activated protein kinases, and
      nuclear translocation of transcription factors. EGB also up-regulated the HO-1
      expression, and the Nrf-2 level in the nucleus and its transactivity.
      Furthermore, reduced pro-inflammatory mediator levels by EGB were inverted in the
      presence of SnPP. The collective results suggest that the anti-inflammatory
      effects of EGB are due to the HO-1 expression via up-regulation of Nrf-2 in RAW
      264.7 cells stimulated by P. gingivalis LPS.

PMID- 22476937
TI  - Alteration of gene expression levels during osteogenic induction of human adipose
      derived stem cells in long-term culture.
AB  - Adipose tissue is a source of multipotent stem cells and it has the ability to
      differentiate into several types of cell lineages such as neuron cells,
      osteogenic and adipogenic cells. Most studies on human adipose-derived stem cells
      (ASCs) have been carried out at the early passages. For clinical usage, ASCs need
      to be expanded in vitro for a period of time to get sufficient cells for
      transplantation into patients. However, the impact of long-term culture on ASCs
      molecular characteristics has not been established yet. Several studies have also
      shown that osteogenic and adipogenic cells have the ability to switch pathways
      during in vitro culture as they share the same progenitor cells. This data is
      important to ensure their functionality and efficacy before being used clinically
      in the treatment of bone diseases. Therefore, we aim to investigate the effect of
      long-term culture on the adipogenic, stemness and osteogenic genes expression
      during osteogenic induction of ASCs. In this study, the molecular characteristics
      of ASCs during osteogenic induction in long-term culture was analysed by
      observing their morphological changes during induction, analysis of cell
      mineralization using Alizarin Red staining and gene expression changes using
      quantitative RT-PCR. Morphologically, cell mineralization at P20 was less
      compared to P5, P10 and P15. Adipogenesis was not observed as negative lipid
      droplets formation was recorded during induction. The quantitative PCR data
      showed that adipogenic genes expression e.g. LPL and AP2 decreased but PPAR-gamma
      was increased after osteogenic induction in long-term culture. Most stemness
      genes decreased at P5 and P10 but showed no significant changes at P15 and P20.
      While most osteogenic genes increased after osteogenic induction at all passages.
      When compared among passages after induction, Runx showed a significant increased
      at P20 while BSP, OSP and ALP decreased at later passage (P15 and P20). During
      long-term culture, ASCs were only able to differentiate into immature osteogenic
      cells.

PMID- 22476938
TI  - Distribution and source analysis of aluminum in rivers near Xi'an City, China.
AB  - To study the status and source of aluminum (Al) contamination, a total of 21
      sampling sites along six rivers near Xi'an City (Shaanxi province, China) were
      investigated during 2008-2010. The results indicated that the average
      concentration of total Al (Al(t)) in the six rivers increased by 1.6 times from
      2008 to 2010. The spatial distribution of Al(t) concentrations in the rivers near
      Xi'an City was significantly different, ranged from 367 MUg/L (Bahe River) to
      1,978 MUg/L (Taiping River). The Al(t) concentration was highest near an
      industrial area for pulp and paper-making (2,773 MUg/L), where the Al level
      greatly exceeded the water quality criteria of both the USA (Criterion Continuous
      Concentration, 87 MUg/L) and Canada (100 MUg/L). The average concentration of
      inorganic monometric aluminum (Al(im)) was 72 MUg/L which would pose threats to
      fishes and other aquatic lives in the rivers. The concentrations of exchangeable
      Al (Al(ex)) in the sediment of the Taiping River sampled were relatively high,
      making it to be an alternative explanation of increasing Al concentrations in the
      rivers near Xi'an City. Furthermore, an increasing Al level has been detected in
      the upstream watershed near Xi'an City in recent years, which might indicate
      another notable pollution source of Al.

PMID- 22476939
TI  - Constitutive activity of the A2A adenosine receptor and compartmentalised cyclic
      AMP signalling fine-tune noradrenaline release.
AB  - Neuroblastoma SH-SY5Y (SH) cells endogenously express A(2A) adenosine receptors
      and can be differentiated into a sympathetic neuronal phenotype, capable of
      depolarisation-dependent noradrenaline release. Using differentiated SH culture,
      we here explored the link between A(2A)-receptor signalling and neurotransmitter
      release. In response to the receptor agonist CGS21680, the cells produced cyclic
      AMP (cAMP), and when depolarised, they released increased amounts of
      noradrenaline. An A(2A)-receptor antagonist, XAC, as well as an inhibitor of cAMP
      dependent protein kinase A (PKA), H89, depressed agonist-dependent release. In
      the presence of XAC or H89, noradrenaline release was found to be below basal
      values. This suggested that release facilitation also owes to constitutive
      receptor activity. We demonstrate that even in the absence of an agonist, the
      native A(2A)-receptor stimulated cAMP production, leading to the activation of
      PKA and enhanced noradrenaline release. Ancillary, non-cAMP-dependent effects of
      the receptor (i.e. phosphorylation of CREB, of Rabphilin3A) were refractory to
      constitutive activation. PKA-dependent facilitation of noradrenaline release was
      recapitulated with membrane-permeable 8-Br-cAMP; in addition to facilitation, 8
      Br-cAMP caused marked inhibition of release, an effect not observed upon receptor
      activation. Inhibition by receptor-independent cAMP was likely due to suppression
      of voltage-dependent calcium current (VDCC) and increased activity of Src-family
      kinases. Receptor-mediated release facilitation was reproduced in the presence of
      tetrodotoxin (blocking action potentials); hence, the signalling occurred at the
      active zone comprising release sites. Our findings thus support (1) presynaptic
      localisation of the A(2A)-receptor and (2) suggest that compartmentalised
      pathways transmit cAMP signalling in order to facilitate depolarisation-dependent
      neurotransmitter release.

PMID- 22476941
TI  - Special issue on cell and molecular biology of purinergic signalling: an
      introduction.

PMID- 22476940
TI  - A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic
      cells in the absence of serum and extracellular ATP.
AB  - The P2X7 receptor is widely recognized to mediate the proinflammatory effects of
      extracellular ATP. However this receptor in the absence of ATP may have a
      function unrelated to inflammation. Our data show that P2X7 expressed on the
      surface of monocyte/macrophages or on epithelial HEK-293 cells greatly augments
      the engulfment of latex beads and live and heat-killed bacteria by effector
      phagocyte in the absence of ATP and serum. The expression of P2X7 on the effector
      also confers the ability to phagocytose apoptotic target cells and an
      accumulation of P2X7 can be seen at the attachment point to the target.
      Activation of the P2X7 receptor by ATP causes a slow dissociation (over 10-15
      min) of nonmuscle myosin from the P2X7 membrane complex and abolishes further
      P2X7-mediated phagocytosis of these targets. The recent crystal structure of the
      homologous zebrafish P2X4 receptor shows an exposed "nose" of the ectodomain
      (residues 115-162) which contains three of the five disulfide bonds conserved in
      all P2X receptors. Three short biotin-labeled peptides mimicking sequence of this
      exposed region bound to apoptotic target cells but not to either viable cells or
      to other target particles. All three peptides contained one or two cysteine
      residues and their replacement by alanine abolished peptide binding. These data
      implicate thiol-disulfide exchange reactions in the initial tethering of
      apoptotic cells to macrophage and establish P2X7 as one of the scavenger
      receptors involved in the recognition and removal of apoptotic cells in the
      absence of extracellular ATP and serum.

PMID- 22476942
TI  - Assessing patients' beliefs about their cancer-related fatigue: validation of an
      adapted version of the Illness Perception Questionnaire.
AB  - Cancer-related fatigue (CRF) is a common and distressing side-effect of cancer
      treatment. The present study developed a brief version of the Illness Perception
      Questionnaire (IPQ) for assessing patients' representations of CRF. Cancer
      patients and survivors (n = 155) completed a revised version of the IPQ as well
      as measures of fatigue severity at two different time-points. Confirmatory factor
      analysis at both Time 1 and 2 showed that the seven-factor solution based on the
      Self-Regulation Model fit the data adequately and factorial invariance over the
      two time-points was supported. The resulting subscales exhibited good internal
      consistency and test-retest reliability. The adapted version of the IPQ shows
      promise for the assessment of patient perceptions regarding CRF. The scale may be
      able to be used clinically to identify if patients have inaccurate or unhelpful
      representations of CRF and to help tailor interventions for persistent fatigue in
      cancer survivors.

PMID- 22476943
TI  - Effects of device and formulation on in vitro performance of dry powder inhalers.
AB  - The study examined the sensitivity of DPI in vitro performance to formulation and
      device changes. Rotahaler/Rotacaps was selected as the reference DPI drug
      product, and Aerolizer was selected as the test device. Since the test device was
      recognized to have much greater efficiency of dispersion, simple modifications to
      both formulation and device were made in an effort to provide a closer match to
      the in vitro performance of the reference product. The modifications included
      varying the drug and lactose particle sizes and/or lactose fine particle content
      in the test formulations, as well as lowering the specific resistance of the test
      device. These modifications were intended to address variables important for drug
      product performance for a defined experimental design and were not intended to
      mimic the extensive formulation and device design strategies that are employed in
      an industrial setting. Formulation and device modifications resulted in a
      modified test product that approached the reference product in the in vitro
      performance.

PMID- 22476944
TI  - Integrating cytosolic phospholipase A2 with oxidative/nitrosative signaling
      pathways in neurons: a novel therapeutic strategy for AD.
AB  - The pathophysiology of Alzheimer's disease (AD) is comprised of complex metabolic
      abnormalities in different cell types in the brain. To date, there are not yet
      effective drugs that can completely inhibit the pathophysiological event, and
      efforts have been devoted to prevent or minimize the progression of this disease.
      Much attention has focused on studies to understand aberrant functions of the
      ionotropic glutamate receptors, perturbation of calcium homeostasis, and toxic
      effects of oligomeric amyloid beta peptides (Abeta) which results in production
      of reactive oxygen and nitrogen species and signaling pathways, leading to
      mitochondrial dysfunction and synaptic impairments. Aberrant phospholipase A(2)
      (PLA(2)) activity has been implicated to play a role in the pathogenesis of many
      neurodegenerative diseases, including AD. However, mechanisms for their modes of
      action and their roles in the oxidative and nitrosative signaling pathways have
      not been firmly established. In this article, we review recent studies providing
      a metabolic link between cytosolic PLA(2) (cPLA(2)) and neuronal excitation due
      to stimulation of ionotropic glutamate receptors and toxic Abeta peptides. The
      requirements for Ca(2+) binding together with its posttranslational modifications
      by protein kinases and possible by the redox-based S-nitrosylation, provide
      strong support for a dynamic role of cPLA(2) in serving multiple functions to
      neurons and glial cells under abnormal physiological and pathological conditions.
      Therefore, understanding mechanisms for cPLA(2) in the oxidative and nitrosative
      pathways in neurons will allow the development of novel therapeutic targets to
      mitigate the detrimental effects of AD.

PMID- 22476945
TI  - Recent developments in the management of T-cell precursor acute lymphoblastic
      leukemia/lymphoma.
AB  - T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma are
      uncommon disorders classified together by the World Health Organization
      classification as "T-lymphoblastic leukemia/lymphoma." This review gives an
      overview on the treatment of these aggressive but curable T cell malignancies in
      adult patients, in order to highlight current developments. The most interesting
      and relevant developments are in our understanding of the genetics of T-ALL/LBL
      and how the genetics relate to clinical outcome. These studies will inform
      clinicians as to which targeted novel agents may be of value and how patients may
      be best risk-stratified to receive them.

PMID- 22476946
TI  - Ouabain-induced cochlear degeneration in rat.
AB  - Ouabain, a potent inhibitor of the Na+/K+-ATPase pump, selectively destroys
      spiral ganglion neurons (SGNs) in gerbils and mice, whereas in guinea pigs it
      preferentially damages cochlear hair cells. To elucidate the effects of ouabain
      on the rat inner ear, a species widely used in research, 5 MUl of 1 or 10 mM
      ouabain was applied to the round window membrane. Distortion product otoacoustic
      emissions (DPOAE) and auditory brainstem responses (ABR) were used to identify
      functional deficits in hair cells and neurons, respectively, and histological
      techniques were used to characterize cochlear pathologies. High-frequency ABR
      thresholds were elevated after treatment with 1 mM ouabain, whereas DPOAEs
      remained normal. In contrast, 10 mM ouabain increased ABR thresholds and reduced
      DPOAE amplitudes. Consistent with the physiological changes, 1 mM ouabain only
      damaged the SGNs and auditory nerve fibers in the basal turn of the cochlea
      whereas 10 mM ouabain destroyed both SGNs and cochlear hair cells; damage was
      greatest near the base and decreased toward the apex. The nuclei of degenerating
      SGNs and hair cells were condensed and fragmented and many cells were TUNEL
      positive, morphological features of apoptotic cell death. Thus, ouabain-induced
      cochlear degeneration in rats is apoptotic and concentration dependent; low
      concentrations preferentially damage SGNs in the base of the cochlea, producing
      an animal model of partial auditory neuropathy, whereas high concentrations
      damage both hair cells and SGNs with damage decreasing from the base toward the
      apex.

PMID- 22476947
TI  - Diabetes and cancer (1): evaluating the temporal relationship between type 2
      diabetes and cancer incidence.
AB  - Substantial evidence suggests that people with type 2 diabetes have an increased
      risk of developing several types of cancers. These associations may be due to a
      number of direct and indirect mechanisms. Observational studies of these
      associations, including the potential role for glucose-lowering therapy, are
      being increasingly reported, but face a number of methodological challenges. This
      paper is the first of two review papers addressing methodological aspects
      underpinning the interpretations of links between diabetes and cancer, and
      suggests potential approaches to study designs to be considered in observational
      studies. This paper reviews factors related to cancer incidence in the diabetic
      population; the second paper relates to studies of cancer mortality.

PMID- 22476948
TI  - Diabetes and cancer (2): evaluating the impact of diabetes on mortality in
      patients with cancer.
AB  - In this paper we address methodological aspects of aetiological importance in the
      link between diabetes and mortality in patients with cancer. We identified nine
      key points on the cancer pathway at which confounding may arise-cancer screening
      use, stage at diagnosis, cancer treatment selection, cancer treatment
      complications and failures, peri-treatment mortality, competing risks for long
      term mortality, effects of type 2 diabetes on anti-cancer therapies, effects of
      glucose-lowering treatments on cancer outcome and differences in tumour biology.
      Two types of mortality studies were identified: (1) inception cohort studies that
      evaluate the effect of baseline diabetes on cancer-related mortality in general
      populations, and (2) cohorts of patients with a cancer diagnosis and pre-existing
      type 2 diabetes. We demonstrate, with multiple examples from the literature, that
      pre-existing diabetes affects presentation, cancer treatment, and outcome of
      several common cancer types, often to varying extents. Diabetes is associated
      with increased all-cause mortality in cancer patients, but the evidence that it
      influences cancer-specific mortality is inconsistent. In the absence of data that
      address the potential biases and confounders outlined in the above framework, we
      caution against the reporting of cancer-related mortality as a main endpoint in
      analyses determining the impact of diabetes and glucose-lowering medications on
      risk of cancer.

PMID- 22476949
TI  - Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic
      insulin sensitivity.
AB  - AIMS/HYPOTHESIS: Sirtuin-1 (SIRT1) is a potential therapeutic target to combat
      insulin resistance and type 2 diabetes. This study aims to identify a microRNA
      (miRNA) targeting SIRT1 to regulate hepatic insulin sensitivity. METHODS:
      Luciferase assay combined with mutation and immunoblotting was used to screen and
      verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were
      measured by real-time PCR. Insulin signalling was detected by immunoblotting and
      glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor
      and SIRT1-deficient hepatocytes. The role of miR-181a in vivo was explored with
      adenovirus and locked nucleic acid antisense oligonucleotides. RESULTS: miR-181a
      targets the 3' untranslated region (3'UTR) of Sirt1 mRNA through a miR-181a
      binding site, and downregulates SIRT1 protein abundance at the translational
      level. miR-181a is increased in insulin-resistant cultured hepatocytes and liver,
      and in the serum of diabetic patients. Overexpression of miR-181a decreases SIRT1
      protein levels and activity, and causes insulin resistance in hepatic cells.
      Inhibition of miR-181a by antisense oligonucleotides increases SIRT1 protein
      levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic
      expression of SIRT1 abrogates the effect of miR-181a on insulin sensitivity, and
      inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the
      improvement in insulin sensitivity induced by antisense miR-181a. In addition,
      overexpression of miR-181a by adenovirus impairs hepatic insulin signalling, and
      intraperitoneal injection of locked nucleic acid antisense oligonucleotides for
      miR-181a improves glucose homeostasis in diet-induced obesity mice.
      CONCLUSIONS/INTERPRETATION: miR-181a regulates SIRT1 and improves hepatic insulin
      sensitivity. Inhibition of miR-181a might be a potential new strategy for
      treating insulin resistance and type 2 diabetes.

PMID- 22476950
TI  - Jasmonic acid (JA) acts as a signal molecule in LaCl(3)-induced baicalin
      synthesis in Scutellaria baicalensis seedlings.
AB  - Rare earth elements (REEs) have been widely used to increase accumulation of
      biomass and secondary metabolites in medicinal plants in China. However, very few
      studies have investigated how REEs mediate secondary metabolism synthesis in
      medicinal plants. Lanthanum (La), an important REE, is known to improve the
      accumulation of secondary metabolites in medicinal plants and is widely
      distributed in China. However, few studies have evaluated the signal transduction
      leading to La-induced secondary metabolism in medicinal plants. In this study,
      LaCl(3) treatment-induced multiple responses in Scutellaria baicalensis
      seedlings, including the rapid generation of jasmonic acid (JA), sequentially
      followed by the enhancement of baicalin production. Direct application of JA also
      promoted the synthesis of baicalin in the absence of LaCl(3). LaCl(3)-induced
      baicalin synthesis was blocked by two different JA synthesis inhibitors. Our
      results showed that JA acts as a signal component within the signaling system
      leading to La-induced baicalin synthesis in S. baicalensis seedlings.

PMID- 22476951
TI  - The immunostimulatory effect of biogenic selenium nanoparticles on the 4T1 breast
      cancer model: an in vivo study.
AB  - Selenium salts as well as elemental selenium nanoparticles are attracting the
      attention of researchers due to their excellent biological properties. The aim of
      the present work was to study immunomodulation by applying elemental Se NPs to
      stimulate the immune response of mice bearing 4 T1 breast cancer tumors. Six- to
      8-week-old female inbred BALB/c mice were divided into two groups of test and
      control, each containing 15 mice. Every day, for 2 weeks prior to tumor
      induction, selenium nanoparticles were orally administered to the mice at a dose
      of 100 MUg/day. Then, 1 * 10(6) cells from a 4 T1 cell line were injected
      subcutaneously to each mouse. Oral nanoparticle administration was continued
      daily for 3 weeks after tumor induction. Different immunological parameters were
      then evaluated including cytokine level, delayed type hypersensitivity (DTH)
      response as well as tumor growth and the survival rates in all treated or
      nontreated animals. The production of Th1 cytokines, such as IFN-gamma and IL-12,
      in spleen cell culture was increased in the test mice-administered selenium
      nanoparticles. The DTH response of test mice also showed a significant increase
      when compared to the control mice. The survival rate was notably higher for the
      selenium nanoparticle-treated mice compared to the control mice. Our results
      suggest that selenium nanoparticle administration can result in considerable
      induction of the Th1 platform of immune response through the elevation of IFN
      gamma and IL-12 and may be a cause for better prognosis in mice with tumors.

PMID- 22476953
TI  - Buyers beware: lead poisoning due to Ayurvedic medicine.
AB  - A 29-year-old man, who recently emigrated from India, presented with a 2-week
      history of abdominal pain, as well as nausea, constipation, and fatigue. He
      underwent removal of a parathyroid adenoma 6 weeks prior to admission and
      received a locally made Indian traditional medicine (Ayurveda) for pain control;
      however, this information was not initially available. He was instructed to take
      approximately 15 g/day. Initial evaluation revealed a normocytic anemia, but
      other workup including imaging and endoscopy was unrevealing. Given his recent
      use of Ayurvedic medicines, we tested for lead poisoning and found a blood lead
      level of 72 mcg/dl. We sent his medicine for analysis and found it had a high
      lead concentration of 36,000 mcg/g, which is over 25,000 times the maximum daily
      dose. He improved with cessation of the medicine and treatment with succimer.
      Lead poisoning can present with a variety of nonspecific signs and symptoms,
      including abdominal pain and anemia. Ayurvedic medicines, as well as traditional
      medicines from other cultures, may be a source of lead or other heavy metals. It
      is essential for physicians to be aware of adverse effects of Ayurvedic medicines
      as they are easily available and increasing in popularity.

PMID- 22476955
TI  - Acute spinal cord injury induces genetic damage in multiple organs of rats.
AB  - Spinal cord injury (SCI) is a devastating condition with important functional and
      psychological consequences. However, the underlying mechanisms by which these
      alterations occur are still not fully understood. The aim of this study was to
      analyze genomic instability in multiple organs in the acute phase of SCI by means
      of single cell gel (comet) assay. Rats were randomly distributed into two groups
      (n = 5): a SHAM and a SCI group killed 24 h after cord transection surgery. The
      results pointed out genetic damage in blood cells as depicted by the tail moment
      results. DNA breakage was also detected in liver and kidney cells after SCI.
      Taken together, our results suggest that SCI induces genomic damage in multiple
      organs of Wistar rats.

PMID- 22476954
TI  - Activation of acetylcholinesterase after U-74389G administration in a porcine
      model of intracerebral hemorrhage.
AB  - Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes.
      Despite high incidence, morbidity and mortality, the precise pathophysiology of
      spontaneous ICH is not fully understood, while there is little data concerning
      the mechanisms that follow the primary insult of the hematoma formation. The
      cholinergic system, apart from its colossal importance as a neurotransmission
      system, seems to also play an important role in brain injury recovery. It has
      been recently suggested that the brain possesses a cholinergic anti-inflammatory
      pathway that counteracts the inflammatory responses after ICH, thereby limiting
      damage to the brain itself. We, herein, report the findings of our study
      concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound
      enzyme involved in cholinergic neurotransmission) in a porcine model of
      spontaneous ICH, with a focus on the first 4 and 24 h following the lesion's
      induction, in combination with a study of the effectiveness of the lazaroid
      antioxidant U-74389G administration. Our study demonstrates the activation of
      AChE activity following U-74389G administration. The lazaroid U-74389G seems to
      be an established neuroprotectant and this is the first report of its supporting
      role in the enhancement of cholinergic response to the induction of ICH.

PMID- 22476956
TI  - The versatility of Delftia sp. isolates as tools for bioremediation and
      biofertilization technologies.
AB  - Two Pb(II)-resistant bacteria isolated from a soil containing 2,500 mg/kg of Pb
      were identified by 16S rRNA sequencing analysis as Delftia sp. and designated as
      3C and 6C. Both isolates grew at a Pb(II) concentration of 62 mg/L and at the
      stationary phase showed a Pb(II)-sorption capability of 10 +/- 1.5 (3C) and 5 +/-
      0.8 (6C) mg/g of biomass. Biochemical properties related to heavy metal
      resistance and plant growth promotion were analyzed and compared with the Cr(VI)
      resistant plant growth-promoting Delftia sp. JD2, previously reported by our
      group. Both isolates and JD2 were resistant to Cr(VI), Pb(II) and many
      antibiotics, produced siderophores and the phytohormone indole-3-acetic, and
      showed clover growth-promoting activity in greenhouse conditions. Interestingly,
      the occurrence of integron class 1 was shown in all isolates. Our results add to
      previous reports and suggest that bacteria of the genus Delftia could be consider
      as good candidates for the design of technologies for cleaning up contaminated
      environments and/or the production of biofertilizers.

PMID- 22476957
TI  - Waging war and scientific progress.

PMID- 22476959
TI  - Analysis of insect cuticular compounds by non-lethal solid phase micro extraction
      with styrene-divinylbenzene copolymers.
AB  - Insect cuticular hydrocarbons including relatively non-volatile chemicals play
      important roles in cuticle protection and chemical communication. The
      conventional procedures for extracting cuticular compounds from insects require
      toxic solvents, or non-destructive techniques that do not allow storage of
      subsequent samples, such as the use of SPME fibers. In this study, we describe
      and tested a non-lethal process for extracting cuticular hydrocarbons with
      styrene-divinylbenzene copolymers, and illustrate the method with two species of
      bees and one species of beetle. The results demonstrate that these compounds can
      be efficiently trapped by Chromosorb(r) (SUPELCO) and that this method can be
      used as an alternative to existing methods.

PMID- 22476958
TI  - Females of the bumblebee parasite, Aphomia sociella, excite males using a
      courtship pheromone.
AB  - Aphomia sociella (Lepidoptera: Pyralidae: Galleriinae) is a parasitic moth of
      bumblebees. Behavioral experiments show that A. sociella females emit
      semiochemicals that influence male pre-mating behavior and serve as a courtship
      pheromone. GC/EAD and two-dimensional GC/MS (GCxGC-TOFMS) analyses of extracts of
      females revealed three antennally active compounds. Comparative GC and GCxGC
      TOFMS analyses of extracts and synthetic standards confirmed the identity of the
      antennally active compounds as hexan-1-ol (1), 6,10,14-trimethylpentadecan-2-one
      (2), and 6,10,14-trimethylpentadecan-2-ol (3). In laboratory bioassays, alcohol 3
      and, at higher doses, ketone 2 initiated male courtship behavior associated with
      ultrasonic production. Hexan-1-ol (1) and ketone 2 enhanced the activity of
      alcohol 3. These data suggest that hexan-1-ol, 6,10,14-trimethylpentadecan-2-ol,
      and 6,10,14-trimethylpentadecan-2-one constitute the female-produced courtship
      pheromone of A. sociella.

PMID- 22476960
TI  - Trade-offs in defensive metabolite production but not ecological function in
      healthy and diseased sponges.
AB  - Diseases of marine organisms, and sponges in particular, are increasingly
      reported worldwide. Prior research indicates that the survival of sponges on
      reefs is due largely to their production of biologically active secondary
      metabolites that provide protection from a diversity of stressors. Aplysina Red
      Band Syndrome (ARBS) is an emerging disease affecting Caribbean rope sponges
      (Aplysina spp.), but it is not known whether secondary metabolites play a role in
      disease susceptibility and resistance. To investigate whether differences in
      secondary metabolites may explain variability in susceptibility to ARBS in
      Aplysina cauliformis, we used high performance liquid chromatography (HPLC) to
      generate chemical profiles from healthy tissue in both healthy and diseased
      sponges, and quantified peak areas for 15 metabolites. Analyses of healthy and
      diseased sponges revealed qualitative and quantitative differences in their
      chemical profiles. Aplysamine-1 and fistularin-3 were produced in significantly
      higher concentrations by healthy sponges, whereas aerothionin and 11
      oxoaerothionin were found only in diseased sponges. At natural concentrations,
      extracts from both healthy and diseased sponges deterred feeding by an omnivorous
      reef fish. Fistularin-3 deterred feeding at concentrations found in healthy
      sponges, but not at concentrations found in diseased sponges. Aerothionin
      deterred feeding at concentrations found in diseased sponges, and may at least
      partially replace the loss of fistularin-3 as a feeding deterrent compound
      following pathogenesis, suggesting a trade-off in the production of feeding
      deterrent compounds. Extracts from healthy and diseased sponges inhibited
      bacterial growth, and both aplysamine-1 and fistularin-3 displayed selective
      antibacterial activity. Despite differences in secondary metabolite production
      between healthy and diseased sponges, the stress associated with ARBS does not
      appear to compromise the ability of A. cauliformis to maintain defenses against
      some of its natural enemies.

PMID- 22476961
TI  - Galectin-3 genetic variants are associated with platinum-based chemotherapy
      response and prognosis in patients with NSCLC.
AB  - AIM: To explore the association between the galectin-3 genetic polymorphisms and
      Platinum-based chemotherapy response as well as the prognosis of non-small cell
      lung cancer (NSCLC). METHOD: Three hundred twenty patients with Stage III (A+B)
      or IV NSCLC were enrolled. A Platinum-based chemotherapy was given to each
      subjects and therapeutic effect was evaluated. The two galectin-3 genetic
      polymorphisms, namely, galectin-3 +191 A>C and +292 A>C, were genotyped. RESULTS:
      The polymorphic genotypes and the allele frequency of galectin-3 +191 A>C were
      not significantly different between responders and non-responders to
      chemotherapy. For galectin-3 +292 A>C, the AA genotype and A allele distribution
      were significantly higher in responders than in non-responders. Logistic
      regression analysis showed CC genotype of galectin-3 +292 presented higher risk
      of being non-responders compared with the AA genotype (OR = 2.96, 95 % CI: 1.55
      5.47; P < 0.001). The overall survival in patients with AA genotype of galectin-3
      +292 were significantly longer than in those with CC genotype (25.6 vs. 19.5
      months, P = 0.013). The hazard ratio for CC genotype of galectin-3 +292 was 2.43
      (95 % CI: 2.03-3.98, compared with AA carriers, P = 0.003). CONCLUSION: The
      galectin-3 genetic polymorphisms of galectin-3 +292, rather than galectin-3 +191,
      were associated with the chemotherapy response and prognosis of NSCLC.

PMID- 22476963
TI  - Pharmacogenetics in older people: what we know and what we need to know.
AB  - The prevalence of therapeutic failures (TFs) and adverse drug reactions (ADRs)
      markedly increased in older subjects. However, both TFs and ADRs did not always
      appear related to the presence of multiple pharmacologic treatments, a common
      status in subjects aged 65 and over. Instead, they seem more related to
      variations in the genes encoding protein metabolizing and transporting drugs.
      Thus, variations in these proteins may account for the inter-individual
      differences observed in drug efficacy, including the most severe clinical
      consequences TFs and ADRs. The genetics of drug metabolizing enzymes (DMEs) and
      drug transporters (DTs) is a very active area of multidisciplinary research,
      overlapping the fields of medicine, biology, pharmacology, and genetics. These
      proteins are virtually responsible for metabolism and disposition, and thus the
      efficacy, of a number of drugs currently used in clinical practice. This article
      explored some basic concepts of the pharmacogenetics of DMEs and DTs. We also
      focused current knowledge of the genetic basis of TFs and ADRs of the most common
      drugs currently used in geriatric clinics. The knowledge of what we know and what
      we need to know is needed to advance the application of pharmacogenetics in
      clinical practice, in order to introduce personalized treatments for elderly
      people.

PMID- 22476962
TI  - Cell culture models for studying the development of Barrett's esophagus: a
      systematic review.
AB  - BACKGROUND: Barrett's esophagus (BE) is a premalignant condition caused by
      chronic gastroesophageal reflux. BE patients have an increased risk of developing
      esophageal adenocarcinoma (EAC). As many aspects of this condition are still
      unknown, there is a need for in vitro models to study BE development. AIM: To
      review the literature on cell lines and incubation conditions for studying BE
      development. METHODS: A literature search was performed using PubMed, EMBASE and
      the Cochrane library, combining the words esophagus, cell line, culture,
      Barrett's, bile, acid, exposure, reflux and adenocarcinoma. RESULTS: A wide range
      of cell lines and incubation conditions to study BE development have been
      reported. The most commonly used cell lines are derived from epithelium from
      patients with BE or EAC. A 25-minute incubation with 200 MUM bile salts induced
      cell proliferation and Akt phosphorylation. However, increased CDX2 and MUC2
      expression was only observed with longer incubations or higher bile salt
      concentrations. Two-hundred MUM bile at pH 6 showed a higher toxicity to EAC
      cells than the same concentration at pH 7. Multiple 5-minute exposures with 200
      MUM bile at pH 4 or pH 7 increased CK8/18 and COX2 in BE epithelial cells.
      CONCLUSIONS: Two-hundred MUM conjugated primary or secondary bile salts at pH 4
      for multiple short exposures is able to induce BE specific factors in BE cell
      lines. In SQ and EAC cell lines; however, higher concentrations of secondary bile
      salts for 8 h are needed to induce BE specific molecules. Due to the high
      variability in reported methods, it is difficult to determine the most effective
      in vitro setup for studying the development of BE.

PMID- 22476965
TI  - Impact of dialysis modality on the survival of end-stage renal disease patients
      with or without cardiovascular disease.
AB  - BACKGROUND: The question of which modality, either peritoneal dialysis (PD) or
      hemodialysis (HD), confers the survival advantage for incident ESRD patients with
      pre-existing cardiovascular disease (CVD) remains unanswered. METHODS: Data used
      in this study were extracted from the National Health Insurance Research Database
      in Taiwan. From 1997 to 2007, incident ESRD patients who underwent dialysis
      longer than three months were selected. The established dialysis modality at day
      90 was used to analyze the impact of dialysis modality on survival. For each PD
      patient indentified, five HD patients matched for age, sex, and year in which the
      patients received their first dialysis treatment were randomly selected. Finally,
      a total of 35 664 patients including 29 720 HD patients and 5944 PD patients were
      selected. The primary outcome was death after commencing dialysis. RESULTS: For
      diabetic ESRD patients with or without coronary artery disease (CAD) or
      congestive heart failure (CHF), patients receiving PD had inferior survival
      compared with those receiving HD (P<.001, adjusted HR=1.34 to 1.43). For
      nondiabetic patients with CAD or CHF, patients receiving PD also had inferior
      survival compared with those receiving HD (adjusted HR=1.30, CI: 1.08 to 1.57;
      adjusted HR=1.31, CI: 1.11 to 1.55). For nondiabetic ESRD patients without CAD or
      CHF, there was no statistically significant difference in survival between PD and
      HD (adjusted HR=1.00, CI: 0.92 to 1.09; adjusted HR=0.98, CI: 0.90 to 1.07).
      CONCLUSIONS: PD was associated with poorer survival among ESRD patients with CVD
      or diabetes mellitus compared with HD.

PMID- 22476964
TI  - Geographical variability of patient characteristics and treatment patterns affect
      outcomes for incident hemodialysis patients.
AB  - BACKGROUND: Geographical differences in disease prevalence and mortality have
      been described in the general population and in chronic kidney disease patients
      in Europe. In this secondary analysis of the Membrane Permeability Outcome (MPO)
      study, we addressed differences in patient and treatment patterns, and whether
      these affect patient outcomes. METHODS: Participating countries were grouped
      according to geographical location; thus study centers in France, Greece, Italy,
      Portugal and Spain were allocated to southern Europe (n=499), and those in all
      other countries (Belgium, Germany, Poland and Sweden) to northern Europe (n=148).
      Descriptive analysis of patient and treatment patterns at study start, as well as
      survival analysis, was performed. RESULTS: In patients from the northern European
      countries, a higher prevalence of diabetes mellitus and of cardiovascular disease
      was observed than in those from southern Europe (diabetes 35.1% vs. 21.0%,
      p=0.0007; cardiovascular disease 40.5% vs. 22.8%, p<0.0001). In northern Europe,
      23% of patients started hemodialysis with a catheter for vascular access, while
      in southern European centers, only 13% did so (p=0.0042). Kaplan-Meier survival
      analysis revealed a lower probability for both all-cause and cardiovascular
      mortality in southern Europe (log-rank test p<0.001). In a Cox proportional
      hazards model, a higher mortality risk was estimated for the northern European
      patients after adjustment for age, sex, membrane permeability, comorbidity index
      and vascular access (hazard ratio = 1.831; 95% confidence interval, 1.282-2.615;
      p=0.0009). CONCLUSIONS: Our study patients from northern Europe showed a higher
      risk profile than those from southern Europe. However, only some of the factors
      can be modified in attempts to lower the mortality risk in this geographical
      area.

PMID- 22476966
TI  - Lanthanum carbonate: a postmarketing observational study of efficacy and safety.
AB  - BACKGROUND: Hyperphosphatemia is associated with morbidity and mortality in
      hemodialysis patients. The use of calcium chelators is restricted by the risk of
      hypercalcemia and vascular calcifications. Sevelamer, a non-calcium chelator, is
      associated with risks of metabolic acidosis and poor compliance. Lanthanum
      carbonate is a non-calcium chelator not associated with these issues. However,
      accumulation in liver and bone has been a reason for concern. METHODS: Adult
      patients (n=112) from 9 hemodialysis centers, with serum phosphorus >5.5 mg/dL
      and on hemodialysis for >1 year, were selected to switch to lanthanum carbonate
      (mean dosage: 2,189 +/- 491 mg/day); 103 completed the study. Laboratory assays
      for serum phosphate, calcium, parathyroid hormone, alkaline phosphatase, gamma
      glutamyl transpeptidase (gammaGT), aspartate transaminase, alanine transaminase
      and plasma bicarbonate were performed monthly. Seven patients underwent a bone
      biopsy for evaluation of lanthanum bone content. RESULTS: Switching to lanthanum
      carbonate led to a reduction in mean serum phosphate levels (-18.2%; p<0.001) and
      calcium * phosphorus product (-17.6%; p<0.0001). There were no important changes
      in other variables, except for an increase in transaminases in 2 patients with
      preexisting liver disease, who discontinued therapy. An increase in plasma
      bicarbonate concentration was observed (p=0.001). Although some lanthanum was
      detected in bone, its distribution did not follow the mineralization front.
      CONCLUSIONS: Lanthanum carbonate is effective and well tolerated, provided that
      recipients do not have preexisting liver disease. After 8 months of treatment,
      lanthanum was not detected in the mineralization front of bone. In hemodialysis
      patients, lanthanum carbonate does not seem to be involved in metabolic bone
      disease.

PMID- 22476967
TI  - P-glycoprotein function at the blood-brain barrier: effects of age and gender.
AB  - PURPOSE: P-glycoprotein (Pgp) is an efflux transporter involved in transport of
      several compounds across the blood-brain barrier (BBB). Loss of Pgp function with
      increasing age may be involved in the development of age-related disorders, but
      this may differ between males and females. Pgp function can be quantified in vivo
      using (R)-[(11)C]verapamil and positron emission tomography. The purpose of this
      study was to assess global and regional effects of both age and gender on BBB Pgp
      function. PROCEDURES: Thirty-five healthy men and women in three different age
      groups were included. Sixty minutes dynamic (R)-[(11)C]verapamil scans with
      metabolite-corrected arterial plasma input curves were acquired. Grey matter time
      activity curves were fitted to a validated constrained two-tissue compartment
      plasma input model, providing the volume of distribution (V (T)) of (R)
      [(11)C]verapamil as outcome measure. RESULTS: Increased V (T) of (R)
      [(11)C]verapamil with aging was found in several large brain regions in men.
      Young and elderly women showed comparable V (T) values. Young women had higher V
      (T) compared with young men. CONCLUSIONS: Decreased BBB Pgp is found with aging;
      however, effects of age on BBB Pgp function differ between men and women.

PMID- 22476968
TI  - Efficient construction of PET/fluorescence probe based on sarcophagine cage: an
      opportunity to integrate diagnosis with treatment.
AB  - PURPOSE: Due to the shortage of established platforms/methods for multimodality
      probe construction, in this study, we developed a heterofunctional chelator,
      BaAn(Boc)Sar, from sarcophagine cage as a general platform for dual-modality
      probe construction. PROCEDURES: A dual-modality probe for positron-emission
      tomography (PET) and fluorescence imaging was synthesized using the developed
      BaAn(Boc)Sar chelator. The c(RGDyK)(2) peptide (denoted as RGD(2)) and
      fluorescence dye Cy5.5 were conjugated with BaAn(Boc)Sar to form BaAnSar-RGD(2)
      Cy5.5. Then, BaAnSar-RGD(2)-Cy5.5 was labeled with (64)Cu in ammonium acetate
      buffer. PET and fluorescent imaging were carried out to evaluate (64)Cu-BaAnSar
      RGD(2)-Cy5.5 in nude mice bearing U87MG glioblastoma xenograft. RESULTS: The
      BaAnSar-RGD(2)-Cy5.5 was labeled with (64)Cu very efficiently in 0.1 M NH(4)OAc
      buffer within 10 min at 37  degrees C in the yield of 86.7 +/- 4.4 % (n = 3). The
      specific activity of (64)Cu-BaBaSar-RGD(2) was controlled at 50-200 mCi/MUmol for
      the consideration of both PET and optical imaging. MicroPET quantification
      analysis shows that the U87MG tumor uptake is 6.41 +/- 0.28, 6.51 +/- 1.45, and
      5.92 +/- 1.57 %ID/g at 1, 4, and 20 h postinjection, respectively. Good
      correlation was obtained between the tumor to muscle ratios measured by the
      radioactivity and fluorescence intensity. As a proof of concept, an animal
      surgery study demonstrated that this dual-modality probe would greatly benefit
      the patients because the PET moiety could be used for tumor detection, and the
      fluorescent moiety would allow image-guided surgery. CONCLUSIONS: Our findings
      demonstrated the effectiveness and feasibility of preparing dual-modality imaging
      probes based on the sarcophagine scaffold. The resulting PET and fluorescent
      imaging probe also holds a great potential for clinical translation.

PMID- 22476969
TI  - Surface geophysical exploration: developing noninvasive tools to monitor past
      leaks around Hanford's tank farms.
AB  - A characterization program has been developed at Hanford to image past leaks in
      and around the underground storage tank facilities. The program is based on
      electrical resistivity, a geophysical technique that maps the distribution of
      electrical properties of the subsurface. The method was shown to be immediately
      successful in open areas devoid of underground metallic infrastructure, due to
      the large contrast in material properties between the highly saline waste and the
      dry sandy host environment. The results in these areas, confirmed by a limited
      number of boreholes, demonstrate a tendency for the lateral extent of the
      underground waste plume to remain within the approximate footprint of the
      disposal facility. In infrastructure-rich areas, such as tank farms, the
      conventional application of electrical resistivity using small point-source
      surface electrodes initially presented a challenge for the resistivity method.
      The method was then adapted to directly use the buried infrastructure,
      specifically the steel-cased wells that surround the tanks, as "long" electrodes
      for both transmission of electrical current and measurements of voltage.
      Overcoming the drawbacks of the long electrode method has been the focus of our
      work over the past 7 years. The drawbacks include low vertical resolution and
      limited lateral coverage. The lateral coverage issue has been improved by
      supplementing the long electrodes with surface electrodes in areas devoid of
      infrastructure. The vertical resolution has been increased by developing borehole
      electrode arrays that can fit within the small-diameter drive casing of a direct
      push rig. The evolution of the program has led to some exceptional advances in
      the application of geophysical methods, including logistical deployment of the
      technology in hazardous areas, development of parallel processing resistivity
      inversion algorithms, and adapting the processing tools to accommodate electrodes
      of all shapes and locations. The program is accompanied by a full set of quality
      assurance procedures that cover the layout of sensors, measurement strategies,
      and software enhancements while insuring the integrity of stored data. The data
      have been shown to be useful in identifying previously unknown contaminant
      sources and defining the footprint of precipitation recharge barriers to retard
      the movement of existing contamination.

PMID- 22476971
TI  - Metabolites of Lactobacillus plantarum 2142 prevent oxidative stress-induced
      overexpression of proinflammatory cytokines in IPEC-J2 cell line.
AB  - Probiotics have already proven beneficial effects in the treatment of several
      intestinal infections, but the underlying mechanisms how the probiotics can
      affect responses of porcine IPEC-J2 enterocytes to oxidative stress remained to
      be elucidated. The immunomodulatory effect of five bacterial strains
      (Lactobacillus plantarum 2142, Lactobacillus casei Shirota, Bifidobacterium
      animalis subsp. lactis BB-12, Bacillus amyloliquefaciens CECT 5940 and
      Enterococcus faecium CECT 4515) on 1 mM peroxide-triggered upregulation of
      interleukin (IL)-8 and tumor necrosis factor alpha (TNF-alpha) level was screened
      by q RT-PCR. Our data revealed that spent culture supernatant (SCS) of L.
      plantarum 2142 had significant lowering effect on IL-8 and TNF-alpha level with
      concomitant promoting activity on protective Hsp70 gene expression. According to
      our results, lactic acid (racemic, D: - and L: -lactic acid) and acetic acid
      produced by lactobacilli had no protective effect in quenching upregulation of
      proinflammatory cytokines. Furthermore, L. plantarum 2142-specific supernatant
      peptides were detected by gel electrophoresis and capillary zone electrophoresis.

PMID- 22476972
TI  - Vapor-induced phase transformations in docetaxel.
AB  - Vapor-induced transformations of docetaxel anhydrous (form D(A)) under ambient
      conditions have been studied using methanol, ethanol, and water as the solvent
      media. The online vapor-induced transformations were monitored by powder X-ray
      diffractometry. New solid forms (solvates/hydrates/anhydrous) of docetaxel
      anhydrous were obtained in stoichiometric ratios which were characterized
      completely using powder X-ray diffraction, differential scanning calorimeter,
      thermogravimetric analysis, and spectroscopic ((13)C solid-state nuclear magnetic
      spectroscopy, solution (1)H NMR, and Fourier transform infrared) techniques. The
      new forms namely methanol solvate (D(M)), ethanol solvate (D(E)), monohydrate
      (D(MH)), trihydrate (D(TH)), and anhydrous (D(AN-I) and D(AN-II)) were identified
      through structural analysis.

PMID- 22476973
TI  - Evaluation of drug release profile from patches based on styrene-isoprene-styrene
      block copolymer: the effect of block structure and plasticizer.
AB  - We prepared pressure-sensitive adhesive (PSA) patches based on styrene-isoprene
      styrene (SIS) thermoplastic elastomer using hot-melt coating method. The liquid
      paraffine is added in the PSA matrices as a plasticizer to moderate the PSA
      properties. Three drugs, methyl salicylate, capsaicin, and diphenhydramine
      hydrochloride are selected as model drugs. The Fourier transform infrared
      spectroscopy, differential scanning calorimetry test, and wide-angle X-ray
      diffraction test indicate a good compatibility between drugs and matrices. Peppas
      equation is used to describe drug release profile. Different drug-matrix
      absorption, as indicative of drug-matrix interaction, accounts for the variation
      in release profiles of different drugs. Furthermore, atomic force microscopy and
      rheological studies of the PSA samples are performed to investigate the effect of
      SIS structure and plasticizer of PSA on drug release behaviors. For methyl
      salicylate and capsaicin, drug diffusion in the PSA matrices is the main factor
      controlled by the release kinetic constant k. The high [SI] diblock content and
      high plasticizer amount in matrix provide the PSA with a homogeneous and soften
      microstructure, resulting in a high diffusion rate. But for water-soluble drugs
      such as diphenhydramine hydrochloride, the release rate is governed by water
      penetration with the competition from diffusion mechanisms.

PMID- 22476975
TI  - Pharmacoeconomics of Alzheimer's disease (AD) treatment with cholinesterase
      inhibitors.
AB  - Until more effective and especially disease-modifying treatments for Alzheimer's
      disease (AD) are available, the therapeutic arsenal consists of cholinesterase
      inhibitors for mild to moderate dementia and memantine for moderate to severe
      dementia. Health economic data make an important contribution to the planning of
      healthcare services and the estimation of the cost of drug reimbursement. As
      such, for cholinesterase inhibitors it is claimed that the direct cost of the
      drug itself is eclipsed by the cost savings associated with delaying
      institutionalisation or delaying the time of progression into a more severe
      disease state. The present manuscript reviews several factors contributing to the
      costs of AD, gives an overview of available studies claiming the cost
      effectiveness of current AD treatments, highlights strengths and weaknesses of
      the aforementioned studies, and discusses the impact of (early) identification
      and treatment of AD. It is concluded that there still is a need for long-term
      follow-up data from prospective cohort studies before the cost-effectiveness of
      cholinesterase inhibitors for AD can be confirmed.

PMID- 22476974
TI  - Vascular calcification: pathophysiology and risk factors.
AB  - Vascular calcification can occur in nearly all arterial beds and in both the
      medial and intimal layers. The initiating factors and clinical consequences
      depend on the underlying disease state and location of the calcification. The
      best studied manifestation is coronary artery calcification, in part because of
      the obvious clinical consequences, but also because of CT-based imaging
      modalities. In the general population, the presence of coronary artery
      calcification increases cardiovascular risk above that predicted by traditional
      Framingham risk factors, suggesting the presence of nontraditional risk factors.
      In patients with chronic kidney disease (CKD), coronary artery calcification is
      more prevalent and markedly more severe than in the general population. In these
      CKD patients, nontraditional risk factors such as oxidative stress, advanced
      glycation end products, and disordered mineral metabolism are also more prevalent
      and more severe and offer mechanistic insight into the pathogenesis of vascular
      calcification.

PMID- 22476976
TI  - Cognitive impairment as unusual first manifestation in late-onset relapsing
      remitting multiple sclerosis.

PMID- 22476977
TI  - Associations of zinc and copper levels in serum and hair with sleep duration in
      adult women.
AB  - Zinc (Zn) and copper (Cu) are essential micronutrients involved in numerous
      metabolic reactions. They are also antagonists of the N-methyl-D-aspartate
      glutamate (NMDA) receptor in the central nervous system, which mediates mood,
      cognition, pain perception, and sleep. However, there have been few studies on
      the effects of Zn and Cu on sleep. A total of 126 adult women were recruited in
      this cross-sectional study. Zn and Cu levels in the serum and hair were measured
      for each subject. The participants completed the 7-day physical activity recall
      questionnaire and the Hospital Anxiety and Depression Scale. The mean hours of
      sleep were compared according to the tertiles of Zn, Cu, and Zn/Cu ratio in the
      serum and hair by analyses of covariance. The participants in the middle tertile
      of Zn and Zn/Cu ratio in the serum had significantly longer sleep duration
      compared to those in the lowest tertile (p<0.05 for each). An increasing Zn/Cu
      ratio in the hair was associated with longer sleep hours (p=0.026), whereas sleep
      duration decreased significantly from the lowest to the highest tertile of hair
      Cu level (p=0.010). The largest percentage of participants with optimal sleep
      duration was observed in the highest tertile of Zn/Cu ratio in the serum and hair
      (p=0.052 and 0.046, respectively). The results of our study suggest that Zn/Cu
      ratio as well as Zn or Cu levels in the serum and hair may be involved in sleep
      duration in adult women.

PMID- 22476978
TI  - Selenium downregulates RAGE and NFkappaB expression in diabetic rats.
AB  - Diabetes is one of the leading causes of death in developed and developing
      countries. Oxidative stress has been proposed to play a crucial role in the
      pathogenesis of diabetic vascular complications. In recent years, selenium has
      been shown to mediate a number of insulinlike actions in a dose-dependent fashion
      both in vitro and in vivo. In this study, the effect of selenium as sodium
      selenite was investigated in streptozotocin-induced diabetic rats at the dose of
      1 MUg sodium selenite/kg body weight. Selenium supplementation restored the
      streptozotocin-induced alterations in the activities of antioxidant enzymes,
      decreased the serum glucose level, glycated hemoglobin content as well as the
      levels of lipid peroxidation products, and downregulated the expressions of both
      NFkB and RAGE. The histopathological studies also reinforce our findings. Hence,
      selenium has a protective role in streptozotocin-induced diabetes mellitus.

PMID- 22476979
TI  - Association of double-positive FOXA1 and FOXP1 immunoreactivities with favorable
      prognosis of tamoxifen-treated breast cancer patients.
AB  - Breast cancer is primarily a hormone-dependent tumor that can be regulated by the
      status of the steroid hormones estrogen and progesterone. Forkhead box A1 (FOXA1)
      is a member of the forkhead box transcription factor family and functions as a
      pioneer factor of the estrogen receptor (ER) in breast cancer. In the present
      study, we demonstrate that FOXA1 mRNA was upregulated by estrogen and that
      estrogen receptor-alpha (ERalpha) recruitment to ER-binding sites in the vicinity
      of the FOXA1 gene was increased by estrogen in ERalpha-positive MCF-7 breast
      cancer cells. The estrogen-induced FOXA1 upregulation was repressed by 4
      hydroxytamoxifen treatment. We also demonstrated that the proliferation and the
      migration of MCF-7 cells were decreased by FOXA1-specific small interfering RNA
      (siRNA; siFOXA1). Furthermore, siFOXA1 decreased the estrogen response element
      driven transcription and the estrogen-dependent upregulation of ERalpha target
      genes in MCF-7 cells. Next, the immunohistochemical analyses of FOXA1 were
      performed using two groups of breast cancer specimens. The nuclear
      immunoreactivity of FOXA1 was detected in 80 (74%) of 108 human invasive breast
      cancers and was negatively correlated with tumor grade and positively correlated
      with hormone receptor status, including ERalpha and progesterone receptor,
      pathological tumor size, and immunoreactivity of FOXP1, another FOX family
      transcription factor. FOXA1 immunoreactivity was significantly elevated in the
      relapse-free breast cancer patients treated with tamoxifen. Notably, the double
      positive immunoreactivities of FOXA1 and FOXP1 were significantly associated with
      a favorable prognosis for the relapse-free and overall survival of patients with
      tamoxifen-treated breast cancer, with lower P values compared with FOXA1 or FOXP1
      immunoreactivity alone. These results suggest that FOXA1 plays an important role
      in the proliferation and migration of breast cancer cells by modulating estrogen
      signaling and that the double-positive immunoreactivities of FOXA1 and FOXP1 are
      associated with a favorable prognosis of tamoxifen-treated breast cancer.

PMID- 22476980
TI  - Natural inhibitors of poly(ADP-ribose) polymerase-1.
AB  - Poly(ADP-ribose) polymerases (PARPs) are enzymes that catalyze the transfer of
      ADP-ribose units from beta-nicotinamide adenine dinucleotide (NAD(+)) to acceptor
      proteins. PARP-1 is responsible for more than 90 % of protein poly-ADP
      ribosylation in the brain and may play a role as a molecular switch for cell
      survival and death. The functional roles of PARP-1 are largely mediated by its
      activation after binding to damaged DNA. Upon binding, PARP-1 activity increases
      rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide. Increased activity
      of PARP-1 can promote DNA repair and its interaction with several transcription
      factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose)
      accumulation and depletion of NAD(+) and ATP which may lead to caspase
      independent apoptotic or necrotic cell death, respectively. Excessive PARP-1
      activity has been implicated in the pathogenesis of numerous clinical conditions
      such as stroke, myocardial infarction, inflammation, diabetes, and
      neurodegenerative disorders. Therefore, it is not surprising that the search for
      PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer)
      has been an active area of research. Beyond medicinal uses, naturally occurring
      PARP-1 inhibitors may also offer a unique preventative means at attenuating
      chronic inflammatory diseases through dietary supplementation. This possibility
      has prompted research for specific, naturally occurring inhibitors of PARP-1.
      Though fewer investigations focus on identifying endogenous inhibitors/modulators
      of PARP-1 activity in vivo, these activities are very important for better
      understanding the complex regulation of this enzyme and the potential long-term
      benefits of supplementation with PARP-1 inhibitors. With this in mind, the focus
      of this article will be on providing a state-of-the-science review on endogenous
      and naturally occurring compounds that inhibit PARP-1.

PMID- 22476981
TI  - NALCN: a regulator of pacemaker activity.
AB  - Pacemaker cells play a fundamental role in generating or regulating many
      essential biological rhythms. Spontaneous pacemaker activity is dependent on the
      function of an array of ion channels expressed in these cells. Recent
      characterization of a Na(+) leak channel (NALCN) has linked to its role in
      conducting the background Na(+) current that depolarizes resting membrane
      properties of pacemaker neurons. NALCN, along with Unc79 and Unc80, forms a
      protein complex that is involved in regulating intrinsic membrane and synaptic
      activities. In this review, we will discuss the current understanding of NALCN
      channel physiology and its role in regulating cell excitability and pacemaker
      activity.

PMID- 22476982
TI  - Protective effects of curcumin on amyloid-beta-induced neuronal oxidative damage.
AB  - To investigate the protective effects of curcumin against amyloid-beta (Abeta)
      induced neuronal damage. Primary rat cortical neurons were cultured with
      different treatments of Abeta and curcumin. Neuronal morphologies, viability and
      damage were assessed. Neuronal oxidative stress was assessed, including
      extracellular hydrogen peroxide and intracellular reactive oxygen species. The
      abilities of curcumin to scavenge free radicals and to inhibit Abeta aggregation
      and beta-sheeted formation are further assessed and discussed. Curcumin preserves
      cell viability, which is decreased by Abeta. The results of changed morphology,
      released Lactate dehydrogenases and cell viability assays indicate that curcumin
      protects Abeta-induced neuronal damage. Curcumin depresses Abeta-induced up
      regulation of neuronal oxidative stress. The treatment sequence impacts the
      protective effect of curcumin on Abeta-induced neuronal damage. Curcumin shows a
      more protective effect on neuronal oxidative damage when curcumin was added into
      cultured neurons not later than Abeta, especially prior to Abeta. The abilities
      of curcumin to scavenge free radicals and to inhibit the formation of beta
      sheeted aggregation are both beneficial to depress Abeta-induced oxidative
      damage. Curcumin prevents neurons from Abeta-induced oxidative damage, implying
      the therapeutic usage for the treatment of Alzheimer's disease patients.

PMID- 22476983
TI  - Controlling cytoplasmic c-Fos controls tumor growth in the peripheral and central
      nervous system.
AB  - Some 20 years ago c-Fos was identified as a member of the AP-1 family of
      inducible transcription factors (Angel and Karin in Biochim Biophys Acta 1072:129
      157, 1991). More recently, an additional activity was described for this protein:
      it associates to the endoplasmic reticulum and activates the biosynthesis of
      phospholipids (Bussolino et al. in FASEB J 15:556-558, 2001), (Gil et al. in Mol
      Biol Cell 15:1881-1894, 2004), the quantitatively most important components of
      cellular membranes. This latter activity of c-Fos determines the rate of membrane
      genesis and consequently of growth in differentiating PC12 cells (Gil et al. in
      Mol Biol Cell 15:1881-1894, 2004). In addition, it has been shown that c-Fos is
      over-expressed both in PNS and CNS tumors (Silvestre et al. in PLoS One
      5(3):e9544, 2010). Herein, it is shown that c-Fos-activated phospholipid
      synthesis is required to support membrane genesis during the exacerbated growth
      characteristic of brain tumor cells. Specifically blocking c-Fos-activated
      phospholipid synthesis significantly reduces proliferation of tumor cells in
      culture. Blocking c-Fos expression also prevents tumor progression in mice intra
      cranially xeno-grafted human brain tumor cells. In NPcis mice, an animal model of
      the human disease Neurofibromatosis Type I (Cichowski and Jacks in Cell 104:593
      604, 2001), animals spontaneously develop tumors of the PNS and the CNS, provided
      they express c-Fos (Silvestre et al. in PLoS One 5(3):e9544, 2010). Treatment of
      PNS tumors with an antisense oligonucleotide that specifically blocks c-Fos
      expression also blocks tumor growth in vivo. These results disclose cytoplasmic c
      Fos as a new target for effectively controlling brain tumor growth.

PMID- 22476984
TI  - Upregulation of metallothioneins after exposure of cultured primary astrocytes to
      silver nanoparticles.
AB  - To test for the prolonged consequences of a short transient exposure of
      astrocytes to silver nanoparticles (AgNP), cultured primary astrocytes were
      incubated for 4 h in the presence of AgNP and the cell viability as well as
      various metabolic parameters were investigated during a subsequent incubation in
      AgNP-free medium. Acute exposure of astrocytes to AgNP led to a concentration
      dependent increase in the specific cellular silver content to up to 46 nmol/mg
      protein, but did not compromise cell viability. During a subsequent incubation of
      the cells in AgNP-free medium, the cellular silver content of AgNP-treated
      astrocytes remained almost constant for up to 7 days. The cellular presence of
      AgNP did neither induce any delayed cell toxicity nor were alterations in
      cellular glucose consumption, lactate production or in the cellular ratio of
      glutathione to glutathione disulfide observed. However, Western blot analysis and
      immunocytochemical staining revealed that AgNP-treated astrocytes strongly
      upregulated the expression of metallothioneins. These results demonstrate that a
      prolonged presence of accumulated AgNP does not compromise the viability and the
      basal metabolism of cultured astrocytes and suggest that the upregulation of
      metallothioneins may help to prevent silver-mediated toxicity that could be
      induced by AgNP-derived silver ions.

PMID- 22476985
TI  - Patient-provider discussions about colorectal cancer screening: who initiates
      elements of informed decision making?
AB  - BACKGROUND: Colorectal cancer (CRC) screening rates remain low among low-income
      minority populations. OBJECTIVE: To evaluate informed decision making (IDM)
      elements about CRC screening among low-income minority patients. DESIGN:
      Observational data were collected as part of a patient-level randomized
      controlled trial to improve CRC screening rates. Medical visits (November 2007 to
      May 2010) were audio-taped and coded for IDM elements about CRC screening. Near
      the end of the study one provider refused recording of patients' visits (33 of
      270 patients). Among all patients in the trial, agreement to be audio taped was
      43.5 % (103/237). Evaluable patient (n = 100) visits were assessed for CRC
      screening discussion occurrence, IDM elements, and who initiated discussion of
      each IDM element. PARTICIPANTS: Patients were African American (72.2 %), female
      (63.7 %), with annual household incomes <$20,000 (60.7 %), without health
      insurance (57.0 %), and limited health literacy (53.7 %). KEY RESULTS: Although
      CRC screening was mentioned during 48 (48 %) visits, no further discussion about
      screening occurred in 23 visits (19 times mentioned by the participant with no
      response from providers). During any visit, the maximum number of IDM elements
      was five; however, only two visits included five elements. The most common IDM
      element discussed in addition to the nature of the decision was the assessment of
      the patient's understanding in 16 (33.3 %) of the visits that included a CRC
      discussion. CONCLUSIONS: A patient activation intervention initiated CRC
      screening discussions with health care providers; however, limited IDM occurred
      about CRC screening during medical visits of minority and low-income patients.

PMID- 22476986
TI  - A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative
      injury following ischemia-reperfusion.
AB  - Vascular peroxidase 1 (VPO1) can utilize reactive oxygen species (ROS) generated
      from NADPH oxidase (NOX) to catalyze peroxidative reactions. This study was
      performed to identify a novel pathway of NOX/VPO1 in mediating the oxidative
      injury following myocardial ischemia reperfusion (IR). In a rat model of
      myocardial IR, the infarct size, serum creatine kinase (CK) activity, apoptosis,
      NOX activity, NOX2 and VPO1 expression were measured. In a cell (rat heart
      derived H9c2 cells) model of hypoxia/reoxygenation (HR), the apoptosis, NOX
      activity, NOX2 and VPO1 expression, and H(2)O(2) and HOCl levels were examined.
      In vivo, IR caused 54.8 +/- 1.7 % infarct size in myocardium accompanied by
      elevated activities of CK, caspase-3 and NOX, up-regulated VPO1 expression and
      high numbers of myocardial apoptotic cells; these effects were attenuated by
      pretreatment with the inhibitor of NOX. In vitro, inhibition of NOX or silencing
      of NOX2 or VPO1 expression significantly suppressed HR-induced cellular apoptosis
      concomitantly with decreased HOCl production. Inhibition of NOX or silencing of
      NOX2 led to a decrease in H(2)O(2) production accompanied by a decrease in VPO1
      expression and HOCl production. However, silencing of VPO1 expression did not
      affect NOX2 expression and H(2)O(2) production. H(2)O(2)-induced VPO1 expression
      was partially reversed by JNK or p38 MAPK inhibitor. Our results demonstrate a
      novel pathway of NOX2/VPO1 in myocardium, where VPO1 coordinates with NOX2 and
      amplifies the role of NOX-derived ROS in oxidative injury following IR.

PMID- 22476987
TI  - Carbon dioxide embolism during laparoscopic surgery.
AB  - Clinically significant carbon dioxide embolism is a rare but potentially fatal
      complication of anesthesia administered during laparoscopic surgery. Its most
      common cause is inadvertent injection of carbon dioxide into a large vein, artery
      or solid organ. This error usually occurs during or shortly after insufflation of
      carbon dioxide into the body cavity, but may result from direct intravascular
      insufflation of carbon dioxide during surgery. Clinical presentation of carbon
      dioxide embolism ranges from asymptomatic to neurologic injury, cardiovascular
      collapse or even death, which is dependent on the rate and volume of carbon
      dioxide entrapment and the patient's condition. We reviewed extensive literature
      regarding carbon dioxide embolism in detail and set out to describe the
      complication from background to treatment. We hope that the present work will
      improve our understanding of carbon dioxide embolism during laparoscopic surgery.

PMID- 22476988
TI  - Cerebrovascular disease and stroke in Korean male adolescent.
AB  - PURPOSE: This study aimed to estimate the prevalence and incidence of
      cerebrovascular disease (CVD) and stroke in Korean male adolescents. MATERIALS
      AND METHODS: The authors reviewed all medical certificates, medical records, and
      radiologic images from the examinations of Korean military conscription from
      January 2008 to May 2011. RESULTS: Of the 101,156 examinees, 40 had CVD and
      stroke during adolescence. The overall prevalence and incidence of CVD and stroke
      was 39.54 cases per 100,000 adolescents and 2.08 cases per 100,000 adolescents
      per year, respectively and these were similar to the worldwide data. There were 3
      cases of aneurysm, 3 cases of dural arteriovenous fistula, 11 cases of
      arteriovenous malformation, 4 cases of cavernous hemangioma, 4 cases of
      cerebrovascular infarction, 16 cases of Moyamoya disease, and 1 case of missing
      data. The incidence of arteriovenous malformation (0.57 cases per 100,000
      adolescents per year) was lower than the incidence for the worldwide general
      population. The incidence of Moyamoya disease was higher than that in any other
      country (15.82 cases per 100,000 adolescents, vs. 0.83 cases per 100,000
      adolescents per year). CONCLUSION: We observed ischemic and hemorrhagic stroke,
      each accounting for approximately half of cases, and high incidence of Moyamoya
      disease with low incidence of arteriovenous malformation in Korean male
      adolescents.

PMID- 22476989
TI  - The localizing and lateralizing value of auras in lesional partial epilepsy
      patients.
AB  - PURPOSE: We investigated the localizing and lateralizing values of auras in
      patients with lesional partial epilepsy on an outpatient basis. MATERIALS AND
      METHODS: A total of 276 subjects were retrospectively selected for this study if
      they had a unilateral single lobar lesion based on magnetic resonance image (MRI)
      results, and their scalp electroencephalography (EEG) findings were not
      discordant with the MRI-defined lobar localization and lateralization. According
      to the lesion locations, subjects were considered as having mesial temporal
      (MTLE), lateral temporal (LTLE), frontal (FLE), parietal (PLE), or occipital
      (OLE) lobe epilepsies. Auras were classified into 13 categories. RESULTS: A
      hundred and seventy-six subjects (63.8%) had experienced at least one aura. FLE
      subjects had the fewest number of auras. Epigastric and psychic auras were
      frequent among MTLE subjects, while visual auras were common in those with PLE
      and OLE. Somatosensory auras and whole body sensations were more frequent in the
      subjects with PLE than those without. Autonomic auras were more common in MTLE
      subjects than in LTLE subjects. Dysphasic auras were more frequently found in
      left-sided epilepsies. Five pairs of aura categories showed concurrent
      tendencies, which were the epigastric and autonomic auras, autonomic and
      emotional auras, visual and vestibular auras, auditory and vestibular auras, and
      whole-body sensation and auditory auras. Autonomic and emotional auras had a
      concurrent tendency in left-sided epilepsies, but not in right-sided epilepsies.
      CONCLUSION: Our results support the previously known localizing value of auras,
      and suggest that dysphasic auras and the association of emotional and autonomic
      auras may have a lateralizing value.

PMID- 22476990
TI  - Lateralization of cognitive functions in aphasia after right brain damage.
AB  - PURPOSE: The lateralization of cognitive functions in crossed aphasia in dextrals
      (CAD) has been explored and compared mainly with cases of aphasia with left
      hemisphere damage. However, comparing the neuropsychological aspects of CAD and
      aphasia after right brain damage in left-handers (ARL) could potentially provide
      more insights into the effect of a shift in the laterality of handedness or
      language on other cognitive organization. Thus, this case study compared two
      cases of CAD and one case of ARL. MATERIALS AND METHODS: The following
      neuropsychological measures were obtained from three aphasic patients with right
      brain damage (two cases of CAD and one case of ARL); language, oral and limb
      praxis, and nonverbal cognitive functions (visuospatial neglect and visuospatial
      construction). RESULTS: All three patients showed impaired visuoconstructional
      abilities, whereas each patient showed a different level of performances for oral
      and limb praxis, and visuospatial neglect. CONCLUSION: Based on the analysis of
      these three aphasic patients' performances, we highlighted the lateralization of
      language, handedness, oral and limb praxis, visuospatial neglect and visuospatial
      constructive ability in aphasic patients with right brain damage.

PMID- 22476991
TI  - Genetic and epileptic features in Rett syndrome.
AB  - PURPOSE: Rett syndrome is a severe neurodevelopmental disorder in females. Most
      have mutations in the methyl-CpG-binding protein 2 (MECP2) gene (80-90%).
      Epilepsy is a significant commonly accompanied feature in Rett syndrome. Our
      study was aimed at comprehensive analysis of genetic and clinical features in
      Rett syndrome patients, especially in regards to epileptic features. MATERIALS
      AND METHODS: We retrospectively reviewed 20 patients who were diagnosed with
      MECP2 mutations at Severance Children's Hospital between January 1995 and July
      2010. All patients met clinical criteria for Rett syndrome. Evaluations included
      clinical features, epilepsy classification, electroencephalography analysis, and
      treatment of seizures. RESULTS: Ages ranged from 3.6 to 14.3 years (7.7+/-2.6).
      Fourteen different types of MECP2 mutations were found, including a novel in
      frame mutation (1153-1188 del36). Fourteen of these patients (70.0%) had
      epilepsy, and the average age of seizure onset was 3.0+/-1.8 years. Epilepsy was
      diverse, including partial seizure in four patients (28.5%), secondarily
      generalized seizure in six (42.8%), generalized tonic seizure in two (14.3%),
      Lennox-Gastaut syndrome in one (7.1%), and myoclonic status in non-progressive
      encephalopathy in one (7.1%). Motor functions were delayed so that only 10
      patients (50.0%) were able to walk independently: five (35.8%) in the epilepsy
      group and five (83.3%) in the non-epilepsy group. Average developmental scale was
      33.5+/-32.8 in the epilepsy group and 44.4+/-21.2 in the non-epilepsy group. A
      clear genotype-phenotype correlation was not found. CONCLUSION: There is a
      tendency for more serious motor impairment and cognitive deterioration in Rett
      syndrome patients with epilepsy.

PMID- 22476992
TI  - Correlations between serum inflammation factors and left ventricular remodeling
      in acute ST segment elevation myocardial infarction.
AB  - PURPOSE: To investigate the changes and correlations of the serum inflammation
      factors levels and left ventricular (LV) structure and function in patients with
      acute ST segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS:
      A prospective study was performed on 70 STEMI patients and 70 control subjects.
      Serum levels of interleukin-6 (IL-6), soluble CD40 ligand (sCD40L),
      metalloproteinase- 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      were measured by sandwich enzyme-linked immunosorbent assay (ELISA), and cardiac
      structure and function were assessed by echocardiography at admission and 3-year
      follow-up. RESULTS: We found that the levels of serum IL-6, sCD40L and MMP-9
      increased steadily among control subjects, remote myocardial infarction and acute
      STEMI patients, and the level of TIMP-1 elevated remarkly at 3-year follow-up
      visit in STEMI. The admission level of serum MMP-9 positively correlated with LV
      end-diastolic and end-diastole volume (r=0.294, p=0.022; r=0.269, p=0.036,
      respectively), and TIMP-1 positively correlated with E/A ratio (r=0.278, p=0.044)
      at 3-year follow-up. CONCLUSION: The study indicates that admission levels of
      serum MMP-9 and TIMP-1 closely correlated with left ventricular structure and
      function, which may be involved in the process of post-infarction remodeling of
      myocardium.

PMID- 22476993
TI  - Correlations between coronary plaque tissue composition assessed by virtual
      histology and blood levels of biomarkers for coronary artery disease.
AB  - PURPOSE: We investigated correlations of coronary plaque composition determined
      by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of
      biomarkers that represent the vulnerability of coronary plaques. MATERIALS AND
      METHODS: Pre- and postprocedural blood levels of high sensitivity C-reactive
      protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin
      were measured in 70 patients with stable angina (SA) or unstable angina (UA) who
      were undergoing percutaneous coronary intervention (PCI) for single lesions. We
      evaluated the data for correlations between these biomarkers and necrotic core
      contents in PCI target lesions analyzed by VH. RESULTS: Clinical characteristics,
      IVUS, VH, and biomarker blood levels were not different between the SA and the UA
      group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and
      lower remodeling index in the SA group (0.98+/-0.09 vs. 1.10+/-0.070, p<0.001).
      Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly
      significant correlation with the absolute volume of the necrotic core (r=0.320,
      p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231,
      p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends
      toward weakly positive correlations with the absolute volume of necrotic core.
      CONCLUSION: We found a weakly positive correlation between the pre-PCI neopterin
      level and necrotic core volume in the PCI-target lesion. The clinical
      implications of our findings need to be investigated in further studies.

PMID- 22476994
TI  - Diagnostic patterns in the evaluation of patients presenting with syncope at the
      emergency or outpatient department.
AB  - PURPOSE: Patterns of syncope evaluation vary widely among physicians and
      hospitals. The aim of this study was to assess current diagnostic patterns and
      medical costs in the evaluation of patients presenting with syncope at the
      emergency department (ED) or the outpatient department (OPD) of a referral
      hospital. MATERIALS AND METHODS: This study included 171 consecutive patients
      with syncope, who visited the ED or OPD between January 2009 and July 2009.
      RESULTS: The ED group had fewer episodes of syncope [2 (1-2) vs. 2 (1-5),
      p=0.014] and fewer prodromal symptoms (81.5% vs. 93.3%, p=0.018) than the OPD
      group. Diagnostic tests were more frequently performed in the ED group than in
      the OPD group (6.2+/-1.7 vs. 5.3+/-2.0; p=0.012). In addition, tests with low
      diagnostic yields were more frequently used in the ED group than in the OPD
      group. The total cost of syncope evaluation per patient was higher in the ED
      group than in the OPD group [823,000 (440,000-1,408,000) won vs. 420,000 (186,000
      766,000) won, p<0.001]. CONCLUSION: There were some differences in the clinical
      characteristics of patients and diagnostic patterns in the evaluation of syncope
      between the ED and the OPD groups. Therefore, a selective diagnostic approach
      according to the presentation site is needed to improve diagnostic yields and to
      reduce the time and costs of evaluation of syncope.

PMID- 22476995
TI  - Comparison of optical coherence tomographic assessment between first- and second
      generation drug-eluting stents.
AB  - PURPOSE: There is a lack of sufficient data in comparison of optical coherence
      tomographic (OCT) findings between first- and second-generation drug-eluting
      stents (DES). Compared to first-generation (i.e., sirolimus- or paclitaxel
      eluting stents), second-generation DESs (i.e., everolimus- or biolinx-based
      zotarolimus-eluting stents) might have more favorable neointimal coverage.
      MATERIALS AND METHODS: Follow-up OCT findings of 103 patients (119 lesions)
      treated with second- generation DESs were compared with those of 139 patients
      (149 lesions) treated with first-generation DESs. The percentage of uncovered or
      malapposed struts, calculated as the ratio of uncovered or malapposed struts to
      total struts in all OCT cross-sections, respectively, was compared between the
      two groups. RESULTS: Both DES groups showed similar suppression of neointimal
      hyperplasia (NIH) on OCT (mean NIH cross-sectional area; second- vs. first
      generation=1.1+/-0.5 versus 1.2+/-1.0 mm2, respectively, p=0.547). However, the
      percentage of uncovered struts of second-generation DESs was significantly
      smaller than that of first-generation DESs (3.8+/-4.8% vs.7.5+/-11.1%,
      respectively, p<0.001). The percentage of malapposed struts was also
      significantly smaller in second-generation DESs than in first-generation DESs
      (0.4+/-1.6% vs.1.4+/-3.7%, respectively, p=0.005). In addition, intra- stent
      thrombi were less frequently detected in second-generations DESs than in first
      generation DESs (8% vs. 20%, respectively, p=0.004). CONCLUSION: This follow-up
      OCT study showed that second-generation DESs characteristically had greater
      neointimal coverage than first-generation DESs.

PMID- 22476996
TI  - Myeloperoxidase expression in acute myeloid leukemia helps identifying patients
      to benefit from transplant.
AB  - PURPOSE: Despite extensive study, the use of allogeneic hematopoietic stem cell
      transplantation in acute myeloid leukemia (AML) vary considerably. The decision
      of which of these options to choose is complex and depends on both clinical and
      molecular variables as well as the availability and histocompatability of donor
      stem cells. So far there is no clear explanation on whether the expression of
      myeloperoxidase (MPO) relates to the prognosis of AML. MATERIALS AND METHODS: We
      retrospectively analyzed the prognostic significance of the MPO expression in the
      140 patients with diagnosed AML treated at a single institution. RESULTS: In our
      study, MPO expression was associated with disease-free survival (DFS) and
      transplant was beneficial to overcome a negative prognostic effect of MPO
      negative at diagnosis based upon the result that the DFS in patients received
      transplants are not significant between the MPO-positive group and MPO-negative
      group although DFS in all patients was different according to MPO expression.
      CONCLUSION: MPO expression at diagnosis helps to choose therapy for each AML
      patient and can differentiate AML patients who need transplantation.

PMID- 22476997
TI  - Clinical outcomes of ductal carcinoma in situ of the breast treated with partial
      mastectomy without adjuvant radiotherapy.
AB  - PURPOSE: Some recent trials suggest that postoperative adjuvant radiotherapy (RT)
      may be safely omitted after breast-conserving surgery (BCS) for some patients
      with ductal carcinoma in situ (DCIS). In this study, we reviewed clinical
      outcomes of patients with DCIS treated with partial mastectomy (PM) without
      adjuvant RT. MATERIALS AND METHODS: Medical records of 28 patients (29 breasts)
      with DCIS who were treated with PM, but without RT, between April 1991 and
      December 2010 were retrospectively analyzed. Based on established criteria (2.0
      cm or less in size and no comedonecrosis), 18 patients were treated without RT
      after PM. Seven patients (8 breasts) who did not receive RT due to refusal were
      also included in this study. Three other patients were excluded because data
      concerning comedonecrosis were not available. RESULTS: For the 25 patients
      included in this study, the mean age of the 18 patients who met the criteria was
      47.9+/-6.2 years, and 47.6+/-12.7 years for the 7 patients who did not. The mean
      sizes of the primary tumors were 0.6+/-0.4 cm and 0.9+/-0.3 cm, respectively, in
      these two groups. Among these 25 patients (26 breasts) treated without RT, we
      observed no ipsilateral breast tumor recurrence or mortality within a mean follow
      up of 84 months. CONCLUSION: Based on this small number of cases, patients with
      DCIS, who were selected for tumor size less than 2 cm and absence of
      comedonecrosis, may be treated successfully with BCS; adjuvant RT may be omitted.

PMID- 22476998
TI  - Recent changes in the clinicopathologic features of Korean men with prostate
      cancer: a comparison with Western populations.
AB  - PURPOSE: The aim of this study was to evaluate the recent changes in the
      clinicopathologic features of prostate cancer in Korea and to compare these
      features with those of Western populations. MATERIALS AND METHODS: We
      retrospectively reviewed the data of 1582 men undergoing radical prostatectomy
      for clinically localized prostate cancer between 1995 and 2007 at 10 institutions
      in Korea for comparison with Western studies. The patients were divided into two
      groups in order to evaluate the recent clinicopathological changes in prostate
      cancer: Group 1 had surgery between 1995 and 2003 (n=280) and Group 2 had surgery
      between 2004 and 2007 (n=1302). The mean follow-up period was 24 months. RESULTS:
      Group 1 had a higher prostate-specific antigen level than Group 2 (10.0 ng/mL vs.
      7.5 ng/mL, respectively; p<0.001) and a lower proportion of biopsy Gleason scores
      <=6 (35.0% vs. 48.1%, respectively; p<0.001). The proportion of patients with
      clinical T1 stage was higher in Group 2 than in Group 1. Group 1 had a lower
      proportion of organ-confined disease (59.6% vs. 68.6%; p<0.001) and a lower
      proportion of Gleason scores <=6 (21.3% vs. 33.0%; p<0.001), compared to Group 2.
      However, the relatively higher proportion of pathologic Gleason scores <=6 in
      Group 2 was still lower than those of Western men, even though the proportion of
      organ-confined disease reached to that of Western series. CONCLUSION: Korean men
      with prostate cancer currently present better clinicopathologic parameters.
      However, in comparison, Korean men still show relatively worse pathologic Gleason
      scores than Western men.

PMID- 22476999
TI  - Comparison of pelvic phased-array versus endorectal coil magnetic resonance
      imaging at 3 Tesla for local staging of prostate cancer.
AB  - PURPOSE: Several studies have demonstrated the superiority of endorectal coil
      magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla
      for local staging of prostate cancer. However, few have studied which evaluation
      is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local
      staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI
      at 3 Tesla. MATERIALS AND METHODS: Between January 2005 and May 2010, 151
      patients underwent radical prostatectomy. All patients were evaluated with either
      pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63
      endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was
      compared with pathologic stage. We calculated the specificity, sensitivity and
      accuracy of each group in the evaluation of extracapsular extension and seminal
      vesicle invasion. RESULTS: Both endorectal coil and pelvic phased-array coil MRI
      achieved high specificity, low sensitivity and moderate accuracy for the
      detection of extracapsular extension and seminal vesicle invasion. There were
      statistically no differences in specificity, sensitivity and accuracy between the
      two groups. CONCLUSION: Overall staging accuracy, sensitivity and specificity
      were not significantly different between endorectal coil and pelvic phased-array
      coil MRI.

PMID- 22477000
TI  - Evaluation of the UniCelTM DxI 800 immunoassay analyzer in measuring five tumor
      markers.
AB  - PURPOSE: Tumor marker concentrations in a given specimen measured by different
      analyzers vary according to assay methods, epitopes for antibodies used, and
      reagent specificities. Although great effort in quality assessment has been
      instituted, discrepancies among results from different analyzers are still
      present. We evaluated the assay performance of the UniCelTM DxI 800 automated
      analyzer in measuring the alpha-fetoprotein (AFP), carcinoembryonic antigen
      (CEA), carbohydrate antigen (CA) 125, CA 15-3 and CA 19-9 tumor markers.
      MATERIALS AND METHODS: The linearity and precision performance of the five tumor
      marker assays were evaluated, and concentrations of the respective markers as
      measured by DxI were compared to those measured by other conventional analyzers
      (ADVIA CentaurTM and VitrosTM ECi) using 200 specimens collected from 100 healthy
      persons and 100 patients with respective cancers. RESULTS: The linear fits for
      all five tumor markers were statistically acceptable (F=4648 for AFP, F=15846 for
      CEA, F=6445 for CA 125, F=2285 for CA 15-3, F=7459 for CA 19-9; p<0.0001 for
      all). The imprecision of each tumor marker assay was less than 5% coefficient of
      variation, except for low and high concentrations of AFP. The results from
      UniCelTM DxI 800 were highly correlated with those from other analyzers.
      CONCLUSION: Our results demonstrate that UniCelTM DxI 800 has good linearity and
      precision performance for the tumor markers assayed in this study. However, there
      were discrepancies between assaying methods. Efforts to standardize tumor marker
      assays should be undertaken, and the redetermination of cut-off levels is
      necessary when developing methods of analyzing tumor markers.

PMID- 22477001
TI  - Prognostic factors for endotracheal silicone stenting in the management of
      inoperable post-intubation tracheal stenosis.
AB  - PURPOSE: Stenting has been developed to deal with airway stenosis and is
      applicable in patients with post-intubation tracheal stenosis (PITS) in whom
      surgery would not be indicated. The purpose of this study was to investigate the
      prognostic factors in inoperable patients in whom a silicone stent was inserted
      due to PITS. MATERIALS AND METHODS: We retrospectively evaluated 55 PITS patients
      undergoing silicone stenting between January 2001 and December 2009. RESULTS:
      Silicone stent was inserted to narrowed trachea after the combination of pre
      dilatation including laser cauterization, mechanical bougienation and ballooning.
      Following airway stabilization, the stent could be removed successfully in 40%
      (22/55) of the patients after median 12 months of stenting. However, in 60%
      (33/55) of patients, the stent could not be removed successfully and surgical
      management was needed after initial stabilization. Multivariate analysis revealed
      that the stent could be successfully removed more frequently in those who do not
      have cardiovascular disease [odds ratio (OR)=12.195; p=0.036] and the
      intervention was performed within 6 months after intubation (OR=13.029; p=0.031).
      CONCLUSION: Among those patients undergoing silicone stenting due to PITS, the
      stent could be successfully removed when patients do not have cardiovascular
      disease and stented within 6 months after intubation.

PMID- 22477002
TI  - Hereditary thrombophilia in Korean patients with idiopathic pulmonary embolism.
AB  - PURPOSE: Hereditary thrombophilia (HT) is a major risk factor for idiopathic
      pulmonary embolism (iPE) and shows different prevalence among ethnic groups. The
      prevalence and clinical characteristics of HT in Korean patients with iPE were
      investigated. MATERIALS AND METHODS: Patients with PE on computed tomography (CT)
      scan were recruited, and those with malignancy were excluded. Patients were
      divided into iPE and provoked PE (pPE) groups. The presence of HT in the iPE
      group was assessed by DNA sequencing of the corresponding gene in patients who
      had low levels of natural anticoagulants. The clinical characteristics of iPE
      with HT (iPE/HT+) were compared with those of iPE without HT (iPE/HT-) and pPE.
      RESULTS: Out of 161 patients, 84 patients had iPE and 77 patients had pPE. Among
      54 patients in the iPE group whose coagulation profiles were tested, 28 patients
      were diagnosed with HT (51.9%; 28/54). Compared with the iPE/HT- and pPE groups,
      the iPE/HT+ group showed the highest proportion of male patients (71.4%;
      p<0.001); the youngest mean age (44+/-14 years; p<0.001); and the highest
      frequencies for history of venous thromboembolism (64.3%; p<0.001), concurrent
      deep vein thrombosis (75.0%; p=0.021), and adverse clinical outcomes (42.9%,
      p<0.001). Protein C deficiency was the most common HT. On molecular genetic
      tests, causative mutation was identified in 13 patients. CONCLUSION: In this
      study of Korean patients, about half of the patients with iPE had HT. Patients
      with iPE and HT were mostly young males with deep venous thrombosis (DVT),
      previous venous thromboembolism (VTE), and frequent adverse clinical outcomes.
      Therefore, Korean patients with iPE should be tested for HT.

PMID- 22477003
TI  - Estimating average glucose levels from glycated albumin in patients with end
      stage renal disease.
AB  - PURPOSE: In patients with diabetic end stage renal disease (ESRD), glycated
      albumin (GA) reflects recent glycemic control more accurately than glycated
      hemoglobin (HbA1c). We evaluated the relationship between GA and average blood
      glucose (AG) level and developed an estimating equation for translating GA values
      into easier-to-understand AG levels. MATERIALS AND METHODS: A total of 185 ESRD
      patients, including 154 diabetic and 31 non-diabetic participants, were enrolled
      (108 hemodialysis, 77 peritoneal dialysis). Patients were asked to perform four
      point daily self-monitoring of capillary blood glucose (SMBG) at least three
      consecutive days each week for four weeks. Serum levels of GA, HbA1c and other
      biochemical parameters were checked at baseline, as well as at 4 and 8 weeks.
      RESULTS: Approximately 74.3+/-7.0 SMBG readings were obtained from each
      participant and mean AG was 169.1+/-48.2 mg/dL. The correlation coefficient
      between serum GA and AG levels (r=0.70, p<0.001) was higher than that of HbA1c
      and AG (r=0.54, p<0.001). Linear regression analysis yielded the following
      equation: estimated AG (eAG) (mg/dL)=4.71*GA%+73.35, and with this formula, serum
      GA levels could be easily translated to eAG levels. Multivariate analysis
      revealed significant contributions of postprandial hyperglycemia (beta=0.25,
      p=0.03) and serum albumin (beta=0.17, p=0.04) in determining serum GA level,
      independent to other clinical parameters. CONCLUSION: Compared to HbA1c, serum GA
      levels were better correlated with AG levels. Using the estimating equation, an
      average blood glucose level of 155-160 mg/dL could be matched to a GA value of 18
      19% in patients with ESRD.

PMID- 22477004
TI  - Urinary hypoxia-inducible factor-1alpha levels are associated with histologic
      chronicity changes and renal function in patients with lupus nephritis.
AB  - PURPOSE: Tubulointerstitial hypoxia in the kidney is considered a hallmark of
      injury and a mediator of the progression of tubulointerstitial fibrosis. Hypoxia
      inducible factor-1alpha (HIF-1alpha), a master transcription factor in cellular
      adaptation to hypoxia, regulates a wide variety of genes, some of which are
      closely associated with tissue fibrosis. The present study set out to
      characterize urinary HIF-1alpha expressions in patients with lupus nephritis (LN)
      and to explore whether urinary HIF-1alpha expressions are associated with
      histologic chronicity changes and renal function. MATERIALS AND METHODS: Urinary
      HIF-1alpha levels were measured by enzyme-linked immunosorbent assays in 42
      patients with LN and in 30 healthy controls. Activity and chronicity indexes as
      well as tubular HIF-1alpha expressions were analyzed for each specimen. RESULTS:
      Urinary HIF-1alpha levels were higher in LN patients than in healthy controls
      (3.977+/-1.696 vs. 2.153+/-0.554 ng/mL, p<0.001) and were associated with
      histologic chronicity indexes (r=0.463, p<0.01) and eGFR (r=-0.324, p<0.05).
      However, urinary HIF-1alpha levels showed no correlation with histologic activity
      indexes, anti-dsDNA, ANA, complement 3 and 4 levels, proteinuria, systemic lupus
      erythematosis disease activity index, and WHO pathological classification
      (p>0.05). CONCLUSION: Urinary HIF-1alpha levels were elevated in LN patients and
      were associated with histologic chronicity changes and renal function, indicating
      that HIF-1alpha might contribute to histologic chronicity in LN.

PMID- 22477005
TI  - Endotoxin is not essential for the development of cockroach induced allergic
      airway inflammation.
AB  - PURPOSE: Cockroach (CR) is an important inhalant allergen and can induce allergic
      asthma. However, the mechanism by which CR induces airway allergic inflammation
      and the role of endotoxin in CR extract are not clearly understood in regards to
      the development of airway inflammation. In this study, we evaluated whether
      endotoxin is essential to the development of CR induced airway allergic
      inflammation in mice. MATERIALS AND METHODS: Airway allergic inflammation was
      induced by intranasal administration of either CR extract, CR with additional
      endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type
      mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR
      4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice. RESULTS: Intranasal
      administration of CR extracts significantly induced airway hyperresponsiveness
      (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell
      hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR
      allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and
      goblet cell hyperplasia of respiratory epithelium; however, it did not affect the
      development of AHR. Endotoxin depletion in CR extract did not attenuate
      eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13
      expression in the lungs compared to CR alone. The attenuation of AHR,
      eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract
      alone was not different between TLR-4 mutant and the wild type mice. In addition,
      heat inactivated CR extract administration induced attenuated AHR and
      eosinophilic inflammation. CONCLUSION: Endotoxin in CR extracts may not be
      essential to the development of airway inflammation.

PMID- 22477006
TI  - Health related quality of life in common variable immunodeficiency.
AB  - PURPOSE: To quantify the health related quality of life in primary
      immunodeficiency patients. MATERIALS AND METHODS: We used generic health status
      and general psychological health questionnaires to determine the range of issues
      that needed to be considered in examining the burden of common variable
      immunodeficiency (CVID). RESULTS: The health status of patients with CVID was
      lower than that observed in normal subjects. Overall, Role-Physical and General
      Health scales correlated with a poorer clinical status. Surprisingly, the
      duration of disease did not influence health status. Being female, older, General
      Health Questionnaire-positive and alexithymic proved to be major risk factors
      associated with a poor health status. Patients with chronic lung disease and
      chronic diarrhea had the lowest values on the Medical Outcome Study, Short Form
      SF-36 (SF-36) scales. Disease severity perception was associated with the General
      Health Questionnaire and alexithymia status. Limitations in daily activities as a
      result of lower physical health were the major problems facing common variable
      immunodeficiency patients. CONCLUSION: Our data underlined the importance of
      conducting a periodical health related quality of life assessment on patients
      with primary antibody deficiencies and, moreover, stressed the necessity of
      providing psychological support to at risk patients.

PMID- 22477007
TI  - Single-stage removal of thoracic dumbbell tumors from a posterior approach only
      with costotransversectomy.
AB  - PURPOSE: Thoracic dumbbell tumors are relatively rare, usually arising from
      neurogenic elements. Methods for surgical removal thereof remain controversial.
      The purpose of this study was to evaluate the surgical results of a single-stage
      posterior approach with laminectomy and costotransversectomy only for the
      management of thoracic dumbbell tumors. MATERIALS AND METHODS: Eight cases of
      thoracic large dumbbell tumor were analyzed retrospectively: seven men and one
      woman (mean age, 49 years). Pathologic findings included schwannoma in five
      patients, neurofibroma in two patients (Recklinghausen in one patient), and
      ganglioneuroma in one patient. All patients underwent single-stage removal of
      dumbbell tumors by a posterior approach followed by laminectomy and
      costotransversectomy combined with instrumentation. Clinical and radiologic
      outcomes were reviewed, thereafter. RESULTS: Operative time ranged from 185 to
      420 minutes (mean, 313 minutes), with estimated blood loss ranging from 71 to
      1830 mL (mean, 658 mL). Postoperative complications included atelectasis in one
      case. All patients had tumors successfully removed with no neurological
      deterioration. Spinal deformities were not observed in any patients at the last
      follow-up (mean, 52 months), with instrumentation. CONCLUSION: Single-stage
      surgery with laminectomy and costotransversectomy may be useful for removing
      thoracic dumbbell tumors without a combined anterior approach.

PMID- 22477008
TI  - Altered cellular kinetics in growth plate according to alterations in weight
      bearing.
AB  - PURPOSE: To examine the effects of change in weight bearing on the growth plate
      metabolism, a simulated animal model of weightlessness was introduced and the
      chondrocytes' cellular kinetics was evaluated. MATERIALS AND METHODS: Unloading
      condition on the hind-limb of Sprague-Dawley rats was created by fixing a tail
      and lifting the hind-limb. Six rats aged 6 weeks old were assigned to each group
      of unloading, reloading, and control groups of unloading or reloading. Unloading
      was maintained for three weeks, and then reloading was applied for another one
      week thereafter. Histomorphometry for the assessment of vertical length of the
      growth plate, 5-bromo-2'-deoxyuridin immunohistochemistry for cellular kinetics,
      and biotin nick end labeling transferase-mediated deoxyuridine triphosphate
      biotin nick end labeling (TUNEL) assay for chondrocytes apoptosis in the growth
      plate were performed. RESULTS: The vertical length of the growth plate and the
      proliferative potential of chondrocytes were decreased in the unloading group
      compared to those of control groups. Inter-group differences were more
      significant in the proliferative and hypertrophic zones. Reloading increased the
      length of growth plate and proliferative potential of chondrocytes. However,
      apoptotic changes in the growth plate were not affected by the alterations of
      weight bearing. CONCLUSION: Alterations in the weight bearing induced changes in
      the chondrocytic proliferative potential of the growth plate, however, had no
      effects on the apoptosis. This may explain why non-weight bearing in various
      clinical situations hampers normal longitudinal bone growth. Further studies on
      the factors for reversibility of chondrocytic proliferation upon variable
      mechanical stresses are needed.

PMID- 22477009
TI  - Altered cellular kinetics in the growth plate of the femoral head of
      spontaneously hypertensive rats.
AB  - PURPOSE: Pathologic changes in the growth plate remain unknown in Legg-Calve
      Perthes (LCP) disease. Spontaneously hypertensive rats have proven to be a good
      model for studying LCP disease. This study investigated the histopathologic
      changes and the expression of vascular endothelial growth factor in the growth
      plate of spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: Sixty SHR
      rats were divided into two groups: those showing osteonecrosis (SHR+n group: 32),
      and those showing normal ossification (SHR-n group: 28). Thirty Wister Kyoto rats
      served as a control. For histomorphological measurement, the length of each zone
      of the growth plate was measured. Cell kinetics was measured by 5-bromo-2'
      deoxyuridin (BrdU) immunohistochemistry and transferase-mediated deoxyuridine
      triphosphate-biotin nick end labeling (TUNEL) assays. Vascular endothelial growth
      factor (VEGF) immunohistochemistry was used to identify of expression of VEGF.
      RESULTS: The lengths of growth plates of the SHR+n group were significantly
      shorter in the initial growth period than those of the other groups. The lowest
      proliferative rate and the highest apoptosis rate were observed in the SHR+n
      group at the initial growth period. The expression of VEGF in the growth plate of
      the SHR group was lower than the control group, and it was lower in the SHR+n
      group than in the SHR-n group. CONCLUSION: The growth plate of the SHR+n group
      was found to be affected by disease process of ischemic necrosis of the femoral
      head, and this might explain the relative overgrowth of the greater trochanter in
      the later stages of LCP disease.

PMID- 22477010
TI  - Reliability of RTVue, Visante, and slit-lamp adapted ultrasonic pachymetry for
      central corneal thickness measurement.
AB  - PURPOSE: To evaluate reliability of Fourier-domain optical coherence tomography
      (OCT) (RTVue), time-domain OCT (Visante), and slit-lamp adapted ultrasonic
      pachymetry (SL-US) in the measurement of central corneal thickness (CCT).
      MATERIALS AND METHODS: Thirty healthy volunteers visited our clinic 3 times and
      fifty eyes were measured by one physician. RTVue and Visante were randomly
      performed, and then SL-US, in which the ultrasound probe was inserted into the
      Goldmann tonometry mount, was done. During the second visit, each measurement was
      repeated 3 times. Measurements on the second visit were averaged, and agreement
      among the instruments was investigated with Bland-Altman plots. RESULTS: RTVue
      showed smaller repeatability coefficient than Visante and SL-US (4.7, 8.3, and
      7.7 MUm, respectively). Intersession reproducibility of RTVue and Visante was
      worse than their repeatability. CCT of RTVue was estimated to be maximally
      different by 11.8 MUm from CCT of Visante and 8.8 MUm from CCT of SL-US. The
      repeatability coefficient of SL-US was 7.7 MUm and its reproducibility was
      similar to the repeatability. CONCLUSION: CCT measured by RTVue showed good
      reliability and generally agreed with Visante and SL-US. SL-US was as reliable as
      triple touching conventional US even with a single touch on the cornea.

PMID- 22477011
TI  - Facial nerve paralysis due to chronic otitis media: prognosis in restoration of
      facial function after surgical intervention.
AB  - PURPOSE: Facial paralysis is an uncommon but significant complication of chronic
      otitis media (COM). Surgical eradication of the disease is the most viable way to
      overcome facial paralysis therefrom. In an effort to guide treatment of this rare
      complication, we analyzed the prognosis of facial function after surgical
      treatment. MATERIALS AND METHODS: A total of 3435 patients with COM, who
      underwent various otologic surgeries throughout a period of 20 years, were
      analyzed retrospectively. Forty six patients (1.33%) had facial nerve paralysis
      caused by COM. We analyzed prognostic factors including delay of surgery, the
      extent of disease, presence or absence of cholesteatoma and the type of surgery
      affecting surgical outcomes. RESULTS: Surgical intervention had a good effect on
      the restoration of facial function in cases of shorter duration of onset of
      facial paralysis to surgery and cases of sudden onset, without cholesteatoma. No
      previous ear surgery and healthy bony labyrinth indicated a good postoperative
      prognosis. CONCLUSION: COM causing facial paralysis is most frequently due to
      cholesteatoma and the presence of cholesteatoma decreased the effectiveness of
      surgical treatment and indicated a poor prognosis after surgery. In our
      experience, early surgical intervention can be crucial to recovery of facial
      function. To prevent recurrent cholesteatoma, which leads to local destruction of
      the facial nerve, complete eradication of the disease in one procedure cannot be
      overemphasized for the treatment of patients with COM.

PMID- 22477012
TI  - Efficacy of epidural analgesia in patients with cancer pain: a retrospective
      observational study.
AB  - PURPOSE: Pain in terminal cancer patients may be refractory to systemic
      analgesics or associated with adverse drug reactions to analgesics. Epidural
      analgesia has been effectively used in such patients for pain control. However,
      this method does not provide pain relief to all patients. The efficacy and
      complications of continuous epidural analgesia were evaluated for expanding
      efficacy in terminal cancer patients. MATERIALS AND METHODS: The charts of
      patients who received epidural analgesia for over 5 years for the control of
      terminal cancer pain were reviewed retrospectively. RESULTS: Ninety-six patients
      received 127 epidural catheters. The mean duration for epidural catheterization
      was 31.5+/-55.6 (5-509) days. The dose of epidural morphine increased by 3.5% per
      day. The efficacy of epidural analgesia at 2 weeks follow up revealed improved
      pain control (n=56), as the morphine equivalent drug dose dropped from 213.4
      mg/day to 94.1 mg/day (p<0.05) at 2 weeks follow up. Accordingly, after 2 weeks
      institution of epidural analgesia, there was a significant reduction in the
      proportion of patients with severe pain, from 78.1% to 19.6% (p<0.05).
      CONCLUSION: Epidural analgesia was an effective pain control method in patients
      with terminal cancer pain, however, a systematized algorithm for the control of
      cancer-related pain in needed.

PMID- 22477013
TI  - Phagocytosis and endocytosis of silver nanoparticles induce interleukin-8
      production in human macrophages.
AB  - Phagocytosis or endocytosis by macrophages is critical to the uptake of fine
      particles, including nanoparticles, in order to initiate toxic effects in cells.
      Here, our data enhance the understanding of the process of internalization of
      silver nanoparticles by macrophages. When macrophages were pre-treated with
      inhibitors to phagocytosis, caveolin-mediated endocytosis, or clathrin-mediated
      endocytosis, prior to exposure to silver nanoparticles, Interleukin-8 (IL-8)
      production was inhibited. Although cell death was not reduced, the inflammatory
      response by macrophages was compromised by phagocytosis and endocytosis
      inhibitors.

PMID- 22477014
TI  - Male pseudohermaphroditism presented with sudden cardiac arrest.
AB  - Torsades de pointes is a life-threatening arrhythmia associated with a number of
      causes, but is very rare among endocrinologic disorders. We report a case of male
      pseudohermaphroditism with hyperaldosteronism due to a 17alpha-hydroxylase
      deficiency presented with sudden cardiac arrest.

PMID- 22477015
TI  - A Trp33Arg mutation at exon 1 of the MYH9 gene in a Korean patient with May
      Hegglin anomaly.
AB  - In this report, we describe a Korean patient with May-Hegglin anomaly from a
      mutation of the MYH9 gene. The proband was a 21-year-old man with
      thrombocytopenia. He did not have a bleeding tendency. His neutrophil count was
      normal at 7490/mm3; however, the neutrophils contained abnormal basophilic
      inclusions in their cytoplasm. The platelet count was decreased at 15,000/mm3
      with giant platelets. Coagulation test results were not remarkable. Direct
      sequencing of MYH9 revealed that he was heterozygous for a mutation in exon 1,
      which was a 97T>A substitution mutation affecting codon 33, substituting
      tryptophan with arginine (Trp33Arg). Family study showed that both of his parents
      had normal phenotype and genotypes, indicating a de novo occurrence of the
      mutation in the proband.

PMID- 22477016
TI  - Syndrome of inappropriate antidiuretic hormone secretion in a patient with large
      cell neuroendocrine carcinoma.
AB  - The syndrome of inappropriate antidiuretic hormone secretion has only been
      reported in a few patients with large cell neuroendocrine carcinoma (LCNEC);
      however, it has never been reported in a patient with LCNEC of the lung, whose
      serum sodium levels were normalized after surgical resection of the mass. A 63
      year-old male presented with a two-day history of dizziness and recent memory
      loss. On admission, his serum sodium level was 113 mEq/L with a serum osmolality
      of 236 mosm/kg, a urine osmolality of 441 mosm/kg, and a urine sodium level of 65
      mEq/L. His chest computed tomography revealed a 2.7*2.3 cm-sized mass in the left
      lower lobe. After surgical removal of the mass, his serum sodium concentrations
      were normalized, and histopathology of the mass revealed LCNEC.

PMID- 22477019
TI  - Structural integrity and postconcussion syndrome in mild traumatic brain injury
      patients.
AB  - The presence of a postconcussion syndrome (PCS) induces substantial socio
      professional troubles in mild traumatic brain injury (mTBI) patients. Although
      the exact origin of these disorders is not known, they may be the consequence of
      diffuse axonal injury (DAI) impacting structural integrity. In the present study,
      we compared structural integrity at the subacute and late stages after mTBI and
      in case of PCS, using diffusion-weighted imaging (DWI). Fifty-three mTBI patients
      were investigated and compared with 40 healthy controls. All patients underwent a
      DWI examination at the subacute (8-21 days) and late (6 months) phases after
      injury. MTBI patients with PCS were detected at the subacute phase using the ICD
      10 classification. Groupwise differences in structural integrity were
      investigated using Tract-Based Spatial Statistics (TBSS). A loss of structural
      integrity was found in mTBI patients at the subacute phase but partially resolved
      over time. Moreover, we observed that mTBI patients with PCS had greater and
      wider structural impairment than patients without PCS. These damages persisted
      over time for PCS patients, while mTBI patients without PCS partly recovered. In
      conclusion, our results strengthen the relationship between structural integrity
      and PCS.

PMID- 22477020
TI  - Reallocating attention during multiple object tracking.
AB  - Wolfe, Place, and Horowitz (Psychonomic Bulletin & Review 14:344-349, 2007) found
      that participants were relatively unaffected by selecting and deselecting targets
      while performing a multiple object tracking task, such that maintaining tracking
      was possible for longer durations than the few seconds typically studied. Though
      this result was generally consistent with other findings on tracking duration
      (Franconeri, Jonathon, & Scimeca Psychological Science 21:920-925, 2010), it was
      inconsistent with research involving cuing paradigms, specifically precues
      (Pylyshyn & Annan Spatial Vision 19:485-504, 2006). In the present research, we
      broke down the addition and removal of targets into separate conditions and
      incorporated a simple performance model to evaluate the costs associated with the
      selection and deselection of moving targets. Across three experiments, we
      demonstrated evidence against a cost being associated with any shift in
      attention, but rather that varying the type of cue used for target deselection
      produces no additional cost to performance and that hysteresis effects are not
      induced by a reduction in tracking load.

PMID- 22477021
TI  - Neither as harmful as feared by critics nor as empowering as promised by
      providers: risk information offered direct to consumer by personal genomics
      companies.
AB  - In this paper, I investigate ethical and policy aspects of the genetic services
      and web-rhetoric of companies offering genetic information direct to consumer,
      and I do so with a special focus on genetic risk information. On their websites,
      the companies stress that genetic risk testing for multifactorial complex medical
      conditions such as cardiovascular disease and cancer may empower the consumer and
      provide valuable input to personal identity. Critics maintain, on the other hand,
      that testing can be psychologically harmful, is of limited clinical and
      preventive value, and vulnerable to misinterpretation. I stress the importance of
      empirical studies in assessing the pros and cons of direct-to-consumer testing
      and point out that recent empirical studies indicate that this testing is neither
      as harmful as feared by critics nor as empowering as promised by the companies.
      However, the testing is not entirely harmless. Remaining problems include testing
      of third parties without consent and ownership of genotypic and phenotypic
      information. Moreover, the testing, although not particularly empowering, may
      still provide input to self-understanding that some people find valuable.
      Regarding policy-making, I suggest that self-regulation in terms of best practice
      guidelines may play an important role, but I also stress that national and
      international regulation may be necessary. 

PMID- 22477023
TI  - Phenylpyruvic acid decreases glucose-6-phosphate dehydrogenase activity in rat
      brain.
AB  - Phenylketonuria is a recessive autosomal disorder that is caused by a deficiency
      in the activity of phenylalanine-4-hydroxylase, which converts phenylalanine to
      tyrosine, leading to the accumulation of phenylalanine and its metabolites
      phenyllactic acid, phenylacetic acid, and phenylpyruvic acid in the blood and
      tissues of patients. Phenylketonuria is characterized by severe neurological
      symptoms, but the mechanisms underlying brain damage have not been clarified.
      Recent studies have shown the involvement of oxidative stress in the
      neuropathology of hyperphenylalaninemia. Glucose-6-phosphate dehydrogenase plays
      an important role in antioxidant defense because it is the main source of reduced
      nicotinamide adenine dinucleotide phosphate (NADPH), providing a reducing power
      that is essential in protecting cells against oxidative stress. Therefore, the
      present study investigated the in vitro effect of phenylalanine (0.5, 1, 2.5, and
      5 mM) and its metabolites phenyllactic acid, phenylacetic acid, and phenylpyruvic
      acid (0.2, 0.6, and 1.2 mM) on the activity of enzymes of the pentose phosphate
      pathway, which is involved in the oxidative phase in rat brain homogenates. 6
      Phosphogluconate dehydrogenase activity was not altered by any of the substances
      tested. Phenylalanine, phenyllactic acid, and phenylacetic acid had no effect on
      glucose-6-phosphate dehydrogenase activity. Phenylpyruvic acid significantly
      reduced glucose-6-phosphate dehydrogenase activity without pre-incubation and
      after 1 h of pre-incubation with the homogenates. The inhibition of glucose-6
      phosphate dehydrogenase activity caused by phenylpyruvic acid could elicit an
      impairment of NADPH production and might eventually alter the cellular redox
      status. The role of phenylpyruvic acid in the pathophysiological mechanisms of
      phenylketonuria remains unknown.

PMID- 22477022
TI  - Design and in vitro haemolytic evaluation of cryptolepine hydrochloride-loaded
      gelatine nanoparticles as a novel approach for the treatment of malaria.
AB  - Cryptolepine hydrochloride-loaded gelatine nanoparticles were developed and
      characterised as a means of exploring formulation techniques to improve the
      pharmaceutic profile of the compound. Cryptolepine hydrochloride-loaded gelatine
      type (A) nanoparticles were developed base on the double desolvation approach.
      After optimisation of formulation parameters including temperature, stirring
      rate, incubation time polymer and cross-linker (glutaraldehyde) concentrations,
      the rest of the study was conducted at two different formulation pH values (2.5
      and 11.0) and by two different approaches to drug loading. Three cryoprotectants-
      sucrose, glucose and mannitol--were investigated for possible use for the
      preparation of freeze-dried samples. Nanoparticles with desired size mostly less
      than 350 nm and zeta potential above +/-20 were obtained when formulation pH was
      between 2.5 and 5 and above 9. Entrapment efficiency was higher at pH 11.0 than
      pH 2.5 and for products formulated when drug was loaded during the second
      desolvation stage compared to when drug was loaded onto pre-formed nanoparticles.
      Further investigation of pH effect showed a new isoelectric point of 6.23-6.27 at
      which the zeta potential of nanoparticles was zero. Sucrose and glucose were
      effective in low concentrations as cryoprotectants. The best formulation produced
      an EC(50) value of 227.4 MUM as a haemolytic agent compared to 51.61 MUM by the
      free compound which is an indication of reduction in haemolytic side effect.
      There was sustained released of the compound from all formulation types over a
      period of 192 h. Stability data indicated that the nanosuspension and freeze
      dried samples were stable at 4 and 25 degrees C, respectively, over a 52-week
      period, but the former was less stable at room temperature. In conclusion,
      cryptolepine hydrochloride-loaded gelatine nanoparticles exhibited reduced
      haemolytic effect compared to the pure compound and can be developed further for
      parenteral delivery.

PMID- 22477024
TI  - Stereoselective chemical defense in the Drosophila parasitoid Leptopilina
      heterotoma is mediated by (-)-iridomyrmecin and (+)-isoiridomyrmecin.
AB  - Chemical defense mechanisms are widespread among insects but have rarely been
      demonstrated in parasitoid wasps. Here, we show that the Drosophila parasitoid
      Leptopilina heterotoma (Hymenoptera, Figitidae) produces (-)-iridomyrmecin and
      (+)-isoiridomyrmecin in a cephalic gland, and that these chemicals have a highly
      repellent effect on ants. Stereoselective synthesis of 4 stereoisomers of
      iridomyrmecin allowed us to demonstrate that the repellent effect of
      iridomyrmecins depends on the stereochemistry. Potential food items impregnated
      with natural doses of (-)-iridomyrmecin were avoided by ants much longer than
      those impregnated with (+)-iridomyrmecin, (+)-isoiridomyrmecin, or (-)
      isoiridomyrmecin, respectively. Quantitative headspace analyses revealed
      furthermore that females and males of L. heterotoma released iridomyrmecins in
      higher amounts when confronted with ants. This is the first time, that (-)
      iridomyrmecin and (+)-isoiridomyrmecin are reported as natural products. Females
      synthesize more iridomyrmecins than males, and the most active (-)-iridomyrmecin
      is produced by females only. We, therefore, hypothesize that this defense
      mechanism is used mainly by female wasps when foraging for Drosophila larvae on
      rotten fruits, but also may protect male wasps during dispersal.

PMID- 22477025
TI  - High conservatism in the composition of scent gland secretions in cyphophthalmid
      harvestmen: evidence from pettalidae.
AB  - The scent gland secretion of Austropurcellia forsteri was analyzed by gas
      chromatography-mass spectrometry, providing the first description of the
      secretion chemistry in the cyphophthalmid family Pettalidae. The secretion
      contained a total of 21 compounds: About 60% of the whole secretion consisted of
      a series of saturated, mono-unsaturated and doubly unsaturated methylketones,
      from C11 to C15, with a cluster of saturated and mono-unsaturated C13
      methylketones dominating. A second fraction included several naphthoquinones such
      as 1,4-naphthoquinone (ca. 20% of secretion), 6-methyl-1,4-naphthoquinone (ca.
      17%), and minor amounts of chloronaphthoquinones (ca. 2%). When compared with
      scent gland compositions of other representatives of cyphophthalmids (e.g. from
      families Sironidae and Stylocellidae), a highly conservative chemistry of
      cyphophthalmid secretions is apparent, based on a restricted number of
      methylketones and naphthoquinones.

PMID- 22477026
TI  - Electrophysiological and behavioral responses of the black-banded oak borer,
      Coroebus florentinus, to conspecific and host-plant volatiles.
AB  - Aspects of the chemical ecology of the black-banded oak borer, (BBOB) Coroebus
      florentinus (Coleoptera: Buprestidae), were studied. Odors produced by males and
      females were similar, both qualitatively and quantitatively. Nonanal, decanal,
      and geranylacetone, identified in the headspace of both sexes, elicited strong
      electroantennographic responses from male antennae, but not from female antennae.
      In dual-choice olfactometer experiments, a blend of these three compounds was
      attractive to both sexes; males responded to decanal alone, while females
      responded to geranylacetone alone, suggesting that these compounds are
      responsible for activity of the blend to the respective sexes. Antennae of both
      sexes responded electroantennographically to the green leaf volatiles (E)-2
      hexenal, (E)-2-hexenol, 1-hexanol, (Z)-3-hexenyl acetate, and n-hexyl acetate,
      all identified from the host plant Quercus suber. In behavioral experiments, only
      females were attracted to host-plant odors, and in tests with synthetic
      compounds, females were attracted to (E)-2-hexenol, 1-hexanol, and (Z)-3-hexenyl
      acetate. It is likely that these compounds play a role in foraging and/or
      oviposition behavior of BBOB females.

PMID- 22477027
TI  - A comparison of classroom and online asynchronous problem-based learning for
      students undertaking statistics training as part of a Public Health Masters
      degree.
AB  - This case-study compared traditional, face-to-face classroom-based teaching with
      asynchronous online learning and teaching methods in two sets of students
      undertaking a problem-based learning module in the multilevel and exploratory
      factor analysis of longitudinal data as part of a Masters degree in Public Health
      at Maastricht University. Students were allocated to one of the two study
      variants on the basis of their enrolment status as full-time or part-time
      students. Full-time students (n = 11) followed the classroom-based variant and
      part-time students (n = 12) followed the online asynchronous variant which
      included video recorded lectures and a series of asynchronous online group or
      individual SPSS activities with synchronous tutor feedback. A validated student
      motivation questionnaire was administered to both groups of students at the start
      of the study and a second questionnaire was administered at the end of the
      module. This elicited data about student satisfaction with the module content,
      teaching and learning methods, and tutor feedback. The module coordinator and
      problem-based learning tutor were also interviewed about their experience of
      delivering the experimental online variant and asked to evaluate its success in
      relation to student attainment of the module's learning outcomes. Student
      examination results were also compared between the two groups. Asynchronous
      online teaching and learning methods proved to be an acceptable alternative to
      classroom-based teaching for both students and staff. Educational outcomes were
      similar for both groups, but importantly, there was no evidence that the
      asynchronous online delivery of module content disadvantaged part-time students
      in comparison to their full-time counterparts.

PMID- 22477029
TI  - High concentration formulation studies of an IgG2 antibody using small angle X
      ray scattering.
AB  - PURPOSE: Concentrated protein formulations are strongly influenced by protein
      protein interactions. These can be probed at low protein concentration by e.g.
      virial coefficients. It was recently suggested that interactions are attractive
      at short distances and repulsive at longer distances. Measurements at low
      concentrations mainly sample longer distances, hence may not predict high
      concentration behavior. Here we demonstrate that small angle X-ray scattering
      (SAXS) measurements simultaneously collect information on interactions at short
      and long distances. METHODS: IgG2 antibody samples at concentrations up to 122
      mg/ml are analyzed using SAXS and compared to Circular Dichroism (CD),
      Fluorescence, Size Exclusion Chromatography (SEC) and Dynamic Light Scattering
      (DLS) analysis. RESULTS: DLS and SEC analyses reveal attraction between
      antibodies at high concentrations. SAXS data analysis provides an elaborate
      understanding and shows both attractive and repulsive forces. The protein-protein
      interactions are strongly affected by excipients. No change in the solution state
      of IgG2 is observed at pH 4-8, while samples at pH 3 exhibit heavy
      oligomerization. The solution conformation of the examined IgG2 derived from SAXS
      data is a T-shape. CONCLUSION: SAXS analysis resolves simultaneous attractive and
      repulsive interactions, and details the effect of excipients on the interactions,
      while providing three-dimensional structural information from low-concentration
      samples.

PMID- 22477030
TI  - The consequences of risk reducing salpingo-oophorectomy: the case for a
      coordinated approach to long-term follow up post surgical menopause.
AB  - Women with germline mutations in BRCA1 and BRCA2 genes have significantly
      increased lifetime risks of breast and ovarian cancer. To manage both the ovarian
      and breast cancer risks the current recommendation is undergo a risk reducing
      salpingo-oophorectomy (RRSO) prior to natural menopause. To date, studies have
      focussed on quality of life and sexual dysfunction in women who undergo RRSO, but
      few have reported on the wider physical consequences. We performed a
      questionnaire study in women with BRCA 1 or 2 gene mutations known to the Peter
      MacCallum Familial Cancer Centre. We gathered information about ovarian surgery,
      ongoing follow-up, management of risk factors including osteoporosis, and current
      severity of menopausal symptoms. Two hundred and nineteen women were surveyed.
      One hundred and forty-three of 157 responding participants (91 %) reported having
      RRSO. Sixty one were pre-menopausal at RRSO. Post surgical follow-up rates were
      generally low, and a minority of women reported recent bone density imaging or
      pharmaceutical prevention or treatment of osteoporosis. Menopausal symptoms
      appeared generally mild. No significant differences in symptom severity were
      observed in women who underwent a pre-menopausal RRSO compared to RRSO after
      natural menopause. These data indicate that a formalised follow-up protocol is
      necessary to optimally manage the consequences of a RRSO.

PMID- 22477031
TI  - The incidence and prevalence of temporomandibular disorders and posterior open
      bite in patients receiving mandibular advancement device therapy for obstructive
      sleep apnea.
AB  - PURPOSE: This study aims to evaluate the incidence and prevalence of
      temporomandibular disorders (TMD) in patients receiving a mandibular advancement
      device (MAD) to treat obstructive sleep apnea using the Research Diagnostic
      Criteria for Temporomandibular Disorders (RDC/TMD). In addition, it also aims to
      assess the development of posterior open bite (POB). MATERIALS AND METHODS: Data
      from 167 patients were evaluated at baseline, from 159 patients after 118 days
      (visit II), from 129 patients after 208 days (visit III), and from 85 patients
      after 413 days (visit IV). The presence of TMD symptoms was evaluated through a
      questionnaire. TMD signs were assessed using the RDC/TMD. Clinical evaluation
      assessed for the presence of POB. RESULTS: The prevalence of TMD was 33/167 (19.8
      %) at baseline. After an initial decrease to 14.5 % on visit II, the prevalence
      increased to 19.4 % on visit III and finally demonstrated a decrease to 8.2 % on
      visit IV. The incidence of TMD was 10.6 % on visit II. This decreased on further
      visits and only two (1.9 %) patients developed TMD from visit III to visit IV.
      POB was found to develop with an average incidence of 6.1 % per visit. The
      prevalence of POB was 5.8 % on visit II, 9.4 % on visit III, and 17.9 % on visit
      IV. CONCLUSION: The use of MADs may lead to the development of TMD in a small
      number of patients. Nevertheless, these signs are most likely transient. Patients
      with pre-existing signs and symptoms of TMD do not experience significant
      exacerbation of those signs and symptoms with MAD use. Furthermore, these may
      actually decrease over time. POB was found to develop in 17.9 % of patients;
      however, only 28.6 % of these patients were aware of any bite changes.

PMID- 22477032
TI  - Cryotherapy is associated with improved clinical outcomes of Sorafenib therapy
      for advanced hepatocellular carcinoma.
AB  - We assessed the safety and efficacy of sorafenib with cryotherapy (cryoRx) in
      advanced hepatocellular carcinoma (HCC). One hundred four HCC patients were
      enrolled, who met the following criteria: (i) Barcelona Clinic Liver Cancer stage
      C; (ii) HCC without distant metastasis; (iii) the presence of portal vein
      thrombosis (PVT); (iv) Child-Pugh class A or B; and (v) life expectancy of at
      least 12 weeks. The patients were randomly divided into sorafenib-cryoRx and
      sorafenib (control) groups. Primary endpoint was time to progression (TTP);
      secondary endpoints included overall survival (OS) and tolerability. Microvessel
      density (MVD) was assessed by CD34-immunostaining. After a median 10.5 (4-26)
      months follow-up, the data showed that median TTP was 9.5 (8.4-13.5) months in
      combinatorial therapy group vs. 5.3 (3.8-6.9) months in sorafenib group (P =
      0.02). The median OS was 12.5 (95 % CI 10.6-16.4) months in combination therapy
      group vs. 8.6 (7.3-10.4) months in sorafenib group (P = 0.01). Low MVD patients
      in combination therapy exhibited significantly longer median TTP and OS than
      controls. High MVD was predictive of poor responses to sorafenib. CryoRx did not
      increase frequency/degree of sorafenib-related adverse events. Therefore, it was
      concluded that the addition of cryoRx significantly improved clinical outcomes of
      Sorafenib therapy in advanced HCC with acceptable tolerance and similar safety
      profiles as previously reported.

PMID- 22477033
TI  - An insecticidal protein from Xenorhabdus ehlersii triggers prophenoloxidase
      activation and hemocyte decrease in Galleria mellonella.
AB  - The bacteria Xenorhabdus spp. are entomopathogenic symbionts that can produce
      several toxic proteins that interfere the immune system of insects. We purified
      an insecticidal protein from Xenorhabdus ehlersii, and designated it as XeGroEL
      with an estimated molecular mass of ~58 kDa. Galleria mellonella larva injected
      with XeGroEL presented prophenoloxidase activation and hemocyte decrease. XeGroEL
      can kill G. mellonella larva in 48 h with an LD(50) of 0.76 +/- 0.08 MUg/larva.
      Our results demonstrate that X. ehlersii possesses a toxic XeGroEL protein acting
      as a potential factor to activate proPO in host insect, which also provides a
      meaningful hypothesis to understand the interaction between nematode-symbiotic
      bacteria and host.

PMID- 22477034
TI  - Augmented humoral immune response and decreased cell-mediated immunity by Aloe
      vera in rats.
AB  - OBJECTIVE: The present study was performed to explore the effect of aqueous
      extract of Aloe vera on parameters of humoral and cell-mediated immunity.
      MATERIALS AND METHODS: Delayed-type hypersensitivity was assessed by measuring
      foot pad thickness following sensitisation by keyhole limpet haemocyanin
      injection and subsequently challenged by the same. Humoral immunity was assessed
      by measurement of haemagglutination titre to sheep red blood cells. RESULTS: Aloe
      vera (400 mg/kg, p.o.) produced a significant decrease in foot pad thickness
      compared with the control group, and also significantly enhanced the secondary
      humoral immune response. CONCLUSION: Thus, these findings suggest that A. vera
      can modulate immune response by augmenting secondary humoral immunity and
      decreasing cell-mediated immunity.

PMID- 22477035
TI  - Pathogens for travelers' diarrhea in Nepal and resistance patterns.
AB  - At the top of the world, Nepal leads the world in travelers' diarrhea. A review
      of the rates, pathogens and resistance patterns over 3 decades reveals a
      persistent problem of increasing alarm. A look at root causes provides insight
      into this oppressive, inconvenient offense to travelers to an otherwise mystical
      Himalayan paradise.

PMID- 22477036
TI  - Recent advances in the diagnosis and treatment of influenza pneumonia.
AB  - A potentially fatal complication of influenza infection is the development of
      pneumonia, caused either directly by the influenza virus, or by secondary
      bacterial infection. Pneumonia related to the 2009 influenza A pandemic was found
      to be underestimated by commonly used pneumonia severity scores in many cases,
      and to be rapidly progressive, leading to respiratory failure. Confirmation of
      etiology by laboratory testing is warranted in such cases. Rapid antigen and
      immunofluorescence testing are useful screening tests, but have limited
      sensitivity. Confirmation of pandemic H1N1 influenza A infection can only be made
      by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) or viral
      culture. The most effective preventive measure is annual influenza vaccination in
      selected individuals. Decisions to administer antiviral medications for influenza
      treatment or chemoprophylaxis should be based upon clinical and epidemiological
      factors, and should not be delayed by confirmatory laboratory testing results.
      Neuraminidase inhibitors (NI) are the agents of choice.

PMID- 22477038
TI  - Clinical ethics and values: how do norms evolve from practice?
AB  - Bioethics laws in France have just undergone a revision process. The bioethics
      debate is often cast in terms of ethical principles and norms resisting emerging
      social and technological practices. This leads to the expression of
      confrontational attitudes based on widely differing interpretations of the same
      principles and values, and ultimately results in a deadlock. In this paper I
      would like to argue that focusing on values, as opposed to norms and principles,
      provides an interesting perspective on the evolution of norms. As Joseph Raz has
      convincingly argued, "life-building" values and practices are closely
      intertwined. Precisely because values have a more indeterminate meaning than
      norms, they can be cited as reasons for action by concerned stakeholders, and
      thus can help us understand how controversial practices, e.g. surrogate
      motherhood, can be justified. Finally, norms evolve when the interpretations of
      the relevant values shift and cause a change in the presumptions implicit in the
      norms. Thus, norms are not a prerequisite of the ethical solution of practical
      dilemmas, but rather the outcome of the decision-making process itself.
      Struggling to reach the right decision in controversial clinical ethics
      situations indirectly causes social and moral values to change and principles to
      be understood differently.

PMID- 22477037
TI  - Chagas disease in non-endemic countries: epidemiology, clinical presentation and
      treatment.
AB  - Imported Chagas disease (Trypanosoma cruzi infection) is increasingly recognized
      as an emerging problem in the USA and Europe due to immigration from Latin
      America. Most migrants from endemic countries will have been infected during
      childhood. Based on the natural history of the disease, up to 35 % of those
      infected may develop cardiac and/or gastrointestinal manifestations during the
      third or fourth decade of life. This disease was described more than 100 years
      ago, yet many challenges still remain such as the identification of risk factors
      for visceral involvement, effective treatment for chronic cases, and reliable
      markers of cure following treatment. Transmission of the infection may occur even
      in non-endemic areas through non-vectorial routes and many countries are
      therefore currently facing the challenge of this emerging public health problem.

PMID- 22477039
TI  - A new era in prenatal testing: are we prepared?
AB  - Prenatal care and the practice of prenatal genetic testing are about to be
      changed fundamentally. Due to several ground-breaking technological developments
      prenatal screening and diagnosis (PND) will soon be offered earlier in gestation,
      with less procedure-related risks and for a profoundly enlarged variety of
      targets. In this paper it is argued that the existing normative framework for
      prenatal screening and diagnosis cannot answer adequately to these new
      developments. In concentrating on issues of informed consent and the reproductive
      autonomy of the pregnant women the ethical debate misses problems related to the
      clinical pathway as a whole and to implicit normative attributions to clinical
      actions or the function of health care professionals. If, however, ethical debate
      would focus on the clinical context and on the ends of PND to a larger extent, it
      would be able to provide a more comprehensive analysis of the ethical challenges
      especially of the new technologies in order to be more adequately prepared for
      their implementation.

PMID- 22477040
TI  - Correspondence in regard to necrotising enterocolitis in a term neonate following
      intravenous immunoglobulin therapy.

PMID- 22477041
TI  - Prenatal diagnosis of LAD-I on cord blood by flowcytometry.
AB  - OBJECTIVES: To optimize a simple flowcytometric technique for Prenatal diagnosis
      (PND) for Leukocyte adhesions defect (LAD-I) on cordocentesis sample at 18 wk
      gestation. METHODS: Normal reference ranges for expression of CD18/CD11-integrins
      in neutrophils and lymphocytes at 18 wk of gestation were established by
      flowcytometry. PND for LAD-I was then performed on the cordocentesis samples in
      three 'at risk' pregnancies after ruling out maternal contamination. RESULTS:
      CD18 and CD11a expression on fetal lymphocytes were found to be the most useful
      parameters for PND of LAD-I. All the three fetuses tested showed normal
      expression of CD18/CD11-integrins and thus were unaffected. This was confirmed by
      testing the cord blood (CB) samples after delivery and normal growth and absence
      of serious infections on follow-up. CONCLUSIONS: Flowcytometry offers a rapid and
      sensitive technique for PND of LAD-I in the absence of facilities for molecular
      diagnosis. Obstetricians, even in developing countries with modest facilities,
      can offer considerable relief for the families.

PMID- 22477042
TI  - Joint control and generalized nonidentity matching: Saying when something is not.
AB  - This study investigated how the absence of a specified stimulus can control
      behavior. Four children were trained in nonidentity matching, and as a control,
      four were trained in identity matching. Both performances were produced by
      training over mediating responses, so that in identity matching, the selection of
      a particular comparison was evoked by the repetition of a sample tact to the
      comparison, and in nonidentity, by the inability to repeat the sample tact to the
      comparison. Successful generalization of the performances indicated that they
      were indeed controlled by these general features rather than by stimulus-specific
      features. Comparison selection thus served as an autoclitic report about other
      verbal behavior. In particular, generalized nonidentity matching indicated that
      sensitivity to discrepancies between what a sample specifies, and what is
      actually presented, can be accounted for behaviorally, without recourse to
      hypothesized cognitive mediators.

PMID- 22477043
TI  - Evocative and function-altering effects of contingency-specifiying stimuli.
AB  - This study examined the effects of various forms of contingency-specifying
      stimuli (CSSs) on the compliance of 4-year-old children, and attempted to
      separate the evocative vs. function-altering functions of the CSSs. Each child
      was presented with a series of CSSs (one per day) that differed with respect to
      the deadline specified (immediate or delayed) and the consequence specified for
      performing the task. In the second part of the experiment, the CSSs either
      specified a delayed deadline or did not specify a deadline. Also, the
      consequences that were specified were either immediate or delayed. The results
      showed that under conditions where the opportunity to respond was immediately
      available, (a) CSSs that specified deadlines and immediate consequences exerted
      reliable control over behavior, and (b) deadlines, whether delayed or immediate
      exerted some control over the behavior, even when CSSs specified no consequences
      for task completion. Under conditions where the opportunity to respond was
      delayed, (a) CSSs of any kind were less likely to exert reliable control, and (b)
      children were most likely to respond when CSSs specified immediate consequences
      and made no mention of a deadline. Results are interpreted in terms of the role
      of CSSs as evocative and/or function-altering and in terms of deadlines as
      learned aversive conditions.

PMID- 22477044
TI  - Effects of visual demonstration, verbal instructions, and prompted verbal
      descriptions on the performance of human subjects in conditional discriminations.
AB  - A study was conducted to confirm prior results concerning the role of prompted
      verbal descriptions of visually demonstrated stimulus relations in the
      acquisition and transfer of identity, difference, and similarity-matching
      relations (Ribes et al., 1988). Four groups of human adults were trained with
      these three matching relations under four different procedures: (1) visual
      demonstration without response requirement, (2) verbal instructions, (3) visual
      demonstration plus prompted verbal description, and (4) visual demonstration plus
      verbal instructions. These procedures were presented at the beginning of the
      training period before subjects could respond to the experimental task. Although
      most subjects in the four groups acquired the conditional discrimination under
      the three matching relations, only those in the two instruction-related groups
      showed some intramodal and extramodal transfer in tests with stimuli that had not
      been used in training. These results suggest the importance of measuring extra
      situational and trans-situational generalization, and raise the need to
      distinguish between formal and functional verbal factors in the regulation of
      human behavior.

PMID- 22477045
TI  - Rule-governed behavior and human behavioral pharmacology: A brief commentary on
      an important topic.
AB  - Over 25 years ago, B. F. Skinner introduced the concept of rule-governed
      behavior, which is the topic of this commentary. To date, behavioral
      pharmacologists have given rule-governed behavior little consideration in their
      analyses of drug action. There are, however, published studies that demonstrate
      the importance of rule-governed behavior in modulating drug effects in humans.
      Rule-governed behavior may help to explain differences in drug self
      administration in humans and nonhumans and, in humans, differences in drug
      effects across individuals and situations. This commentary suggests that rule
      governed behavior merits further attention in the context of human behavioral
      pharmacology, and posits that scientists who are experts in verbal behavior can
      make a unique contribution to the theoretical and experimental analysis of drug
      related human behaviors, including drug abuse and its treatment.

PMID- 22477046
TI  - Verbal concept "mediators" as simple operants.
AB  - A series of experiments is summarized, in historical rather than logical order.
      The results of these experiments indicate that one type of verbal operant, the
      notate, a discriminated verbal response(1) by a subject to stimuli experimentally
      presented, occurs in at least four kinds of situations, "concept-identification,"
      "problem-solving," "association" and "conditioning." In two of these it becomes
      chained with other such operants, to form the notant-a fuller verbal statement
      about the environment, or the monent-a self-administered instruction, that is, an
      S(D) for further behavior. All three classes of operant, each behaving slightly
      differently from one another in behavior, seem to constitute the behavioral basis
      of statements about "hypotheses." Unlike "mediating responses," or "processes,"
      these verbal behaviors are not theoretically inferred, or indirectly manipulated,
      but rather are subject to direct experimental investigation. The relationship of
      their strength to the strength of the behaviors that they control is
      demonstrable.

PMID- 22477047
TI  - The behavior of the listener, generic extensions, and the communicative adequacy
      of verbal behavior.
AB  - Except for a few words, children first become listeners of a word before becoming
      speakers of the word. The analysis of listener behavior is therefore of
      fundamental importance for the complete analysis of verbal behavior. In this
      paper, some basic aspects of listener behavior are examined: in particular, the
      events that give origin to the behavior, the generic effects of these events, and
      intraspecific uniformities between these effects. By relying on the generic
      effects, the notion of extension is defined. This notion is then used for
      characterizing correct listener behavior. Finally, the uniformities between the
      generic effects are shown to play a crucial role in ensuring the communicative
      adequacy of verbal behavior.

PMID- 22477048
TI  - Aspects of conversational style-linguistic versus behavioral analysis.
AB  - Skinner's functional analysis of verbal behavior has been contrasted with formal
      linguistic analysis which studies the grammatical structure and "meaning" of
      verbal response-products, regardless of the circumstances under which they are
      produced. Nevertheless, it appears that certain areas of linguistic analysis are
      not entirely structural. In her recent books That's Not What I Meant (1986) and
      You Just Don't Understand (1990), the linguist Deborah Tannen purports to explain
      how people exhibit different "conversation styles"-that is, how they speak and
      achieve effects on listeners in different ways. There are indications, however,
      that the linguistic model may not be the most functional and precise one that
      could be used in analyzing conversational style. This paper takes concepts
      presented in Deborah Tannen's book That's Not What I Meant (1986), analyzes them
      from a linguistic and a behavioral perspective, and compares the relative utility
      of the two approaches.

PMID- 22477049
TI  - Verbal behavior: The other reviews.
AB  - The extensive attention devoted to Noam Chomsky's review of Verbal Behavior by
      B.F. Skinner has resulted in a neglect of more than a dozen other rewiews of the
      work. These are surveyed and found to be positive and congenial in tone, with
      many of the reviewers advancing his/her own analysis of speech and language. The
      dominant criticism of the book was its disregard of central or implicit processes
      and its lack of experimental data. An examination of the receptive history of
      Verbal Behavior offers a more balanced historical account than those which rely
      excessively on Chomsky's commentary.

PMID- 22477050
TI  - A brief introduction to the word associate test.
AB  - An examination format assessing the intraverbal repertoire of individuals in
      psychology is described and results using it reported. The Associate Test is easy
      to prepare, to take, and to grade. Its reliability measures are satisfactory; its
      ability to predict later behavior is reported upon. The Associate Test is
      computer friendly, and its methods can be applied for examination in any field,
      and at any level.

PMID- 22477051
TI  - Intelligence: Real or artificial?
AB  - Throughout the history of the artificial intelligence movement, researchers have
      strived to create computers that could simulate general human intelligence. This
      paper argues that workers in artificial intelligence have failed to achieve this
      goal because they adopted the wrong model of human behavior and intelligence,
      namely a cognitive essentialist model with origins in the traditional
      philosophies of natural intelligence. An analysis of the word "intelligence"
      suggests that it originally referred to behavior-environment relations and not to
      inferred internal structures and processes. It is concluded that if workers in
      artificial intelligence are to succeed in their general goal, then they must
      design machines that are adaptive, that is, that can learn. Thus, artificial
      intelligence researchers must discard their essentialist model of natural
      intelligence and adopt a selectionist model instead. Such a strategic change
      should lead them to the science of behavior analysis.

PMID- 22477052
TI  - Natural language processing, pragmatics, and verbal behavior.
AB  - Natural Language Processing (NLP) is that part of Artificial Intelligence (AI)
      concerned with endowing computers with verbal and listener repertoires, so that
      people can interact with them more easily. Most attention has been given to
      accurately parsing and generating syntactic structures, although NLP researchers
      are finding ways of handling the semantic content of language as well. It is
      increasingly apparent that understanding the pragmatic (contextual and
      consequential) dimension of natural language is critical for producing effective
      NLP systems. While there are some techniques for applying pragmatics in computer
      systems, they are piecemeal, crude, and lack an integrated theoretical
      foundation. Unfortunately, there is little awareness that Skinner's (1957) Verbal
      Behavior provides an extensive, principled pragmatic analysis of language. The
      implications of Skinner's functional analysis for NLP and for verbal aspects of
      epistemology lead to a proposal for a "user expert"-a computer system whose area
      of expertise is the long-term computer user. The evolutionary nature of behavior
      suggests an AI technology known as genetic algorithms/programming for
      implementing such a system.

PMID- 22477053
TI  - Behavioral personal digital assistants: The seventh generation of computing.
AB  - Skinner (1985) described two divergent approaches to developing computer systems
      that would behave with some approximation to intelligence. The first approach,
      which corresponds to the mainstream of artificial intelligence and expert
      systems, models intelligence as a set of production rules that incorporate
      knowledge and a set of heuristics for inference and symbol manipulation. The
      alternative is a system that models the behavioral repertoire as a network of
      associations between antecedent stimuli and operants, and adapts when supplied
      with reinforcement. The latter approach is consistent with developments in the
      field of "neural networks." The authors describe how an existing adaptive network
      software system, based on behavior analysis and developed since 1983, can be
      extended to provide a new generation of software systems capable of acquiring
      verbal behavior. This effort will require the collaboration of the academic and
      commercial sectors of the behavioral community, but the end result will enable a
      generational change in computer systems and support for behavior analytic
      concepts.

PMID- 22477054
TI  - Modified biliopancreatic diversion for GK rats: a proposal for a simpler
      technique and mechanism research.

PMID- 22477055
TI  - Epidemiological profiles between equol producers and nonproducers: a genomewide
      association study of the equol-producing phenotype.
AB  - Equol is a daidzein (a phytoestrogen isoflavone) metabolite of gut bacteria, and
      the ability to produce equol varies between individuals and reduces the risks of
      several diseases. We tested the effects of equol production on health in Koreans
      and identified the genetic factors that determine the equol-producing phenotype.
      In 1391 subjects, the equol-producing phenotype was determined, based on
      measurements of serum equol concentrations. The anthropometric and blood
      biochemical measurements between equol producers and nonproducers were analyzed
      by LC-MS/MS. Genetic factors were identified in a genomewide association study
      (GWAS), and the interaction between genetic factors and the equol-producing
      phenotype was examined. We observed that 70.1 % of the study population produced
      equol. Blood pressure was significantly lower in equol producers (beta +/- SE = 
      1.35 +/- 0.67, p = 0.045). In our genomewide association study, we identified 5
      single-nucleotide polymorphisms (p < 1 * 10(-5)) in HACE1. The most significant
      SNP was rs6927608, and individuals with a minor allele of rs6927608 did not
      produce equol (odds ratio = 0.57 (95 % CI 0.45-0.72), p value = 2.5 * 10(-6)).
      Notably, the interaction between equol production and the rs6927608 HACE1 SNP was
      significantly associated with systolic blood pressure (p value = 1.3 * 10(4)).
      Equol production is linked to blood pressure, and HACE1, identified in our
      (GWAS), might be a determinant of the equol-producing phenotype.

PMID- 22477056
TI  - Dissociation of first- and second-order motion systems by perceptual learning.
AB  - Previous studies investigating transfer of perceptual learning between luminance
      defined (LD) motion and texture-contrast-defined (CD) motion tasks have found
      little or no transfer from LD to CD motion tasks but nearly perfect transfer from
      CD to LD motion tasks. Here, we introduce a paradigm that yields a clean double
      dissociation: LD training yields no transfer to the CD task, but more
      interestingly, CD training yields no transfer to the LD task. Participants were
      trained in two variants of a global motion task. In one (LD) variant, motion was
      defined by tokens that differed from the background in mean luminance. In the
      other (CD) variant, motion was defined by tokens that had mean luminance equal to
      the background but differed from the background in texture contrast. The task was
      to judge whether the signal tokens were moving to the right or to the left. Task
      difficulty was varied by manipulating the proportion of tokens that moved
      coherently across the four frames of the stimulus display. Performance in each of
      the LD and CD variants of the task was measured as training proceeded. In each
      task, training produced substantial improvement in performance in the trained
      task; however, in neither case did this improvement show any significant transfer
      to the nontrained task.

PMID- 22477057
TI  - Does response interference depend on the subjective visibility of flanker
      distractors?
AB  - Response interference (or response conflict) refers to the phenomenon whereby
      response times to a target stimulus are longer in the presence of distractor
      stimuli that indicate contrary motor responses. Response interference has been
      observed even when the distractor stimuli cannot be discriminated above chance
      levels. These results raise the question of whether response interference might
      be driven automatically by the physical distractor stimuli, independently of
      one's subjective perception of the distractors. Using a modified version of the
      Eriksen flanker task, we applied metacontrast masks to the flanker stimuli and
      measured their subjective visibility after each trial. We found converging lines
      of evidence that the subjective perception of flankers contributed to response
      interference, over and above the contribution of automatic processing of the
      stimulus itself. A factorial analysis revealed that the objective, physical
      congruency of target and flankers and the subjective, perceptual congruency of
      target and flankers make additive, noninteracting contributions to target
      response interference, suggesting that the two interference effects originate
      from independent levels or stages of cognitive processing.

PMID- 22477058
TI  - The plateau in mnemonic resolution across large set sizes indicates discrete
      resource limits in visual working memory.
AB  - The precision of visual working memory (WM) representations declines
      monotonically with increasing storage load. Two distinct models of WM capacity
      predict different shapes for this precision-by-set-size function. Flexible
      resource models, which assert a continuous allocation of resources across an
      unlimited number of items, predict a monotonic decline in precision across a
      large range of set sizes. Conversely, discrete-resource models, which assert a
      relatively small item limit for WM storage, predict that precision will plateau
      once this item limit is exceeded. Recent work has demonstrated such a plateau in
      mnemonic precision. Moreover, the set size at which mnemonic precision reached
      asymptote has been strongly predicted by estimated item limits in WM. In the
      present work, we extend this evidence in three ways. First, we show that this
      empirical pattern generalizes beyond orientation memory to color memory. Second,
      we rule out encoding limits as the source of discrete limits by demonstrating
      equivalent performance across simultaneous and sequential presentations of the
      memoranda. Finally, we demonstrate that the analytic approach commonly used to
      estimate precision yields flawed parameter estimates when the range of stimulus
      space is narrowed (e.g., a 180o rather than a 360o orientation space) and typical
      numbers of observations are collected. Such errors in parameter estimation
      reconcile an apparent conflict between our findings and others based on different
      stimuli. These findings provide further support for discrete-resource models of
      WM capacity.

PMID- 22477059
TI  - Exploiting illusory effects to disclose similarities in numerical and luminance
      processing.
AB  - Recent studies have suggested that numerical and physical magnitudes are
      similarly processed by a generalized magnitude system. The present study
      investigates the number-luminance interaction, taking advantage of illusory
      effects in a cued line bisection task with numerical or nonnumerical flankers and
      varying levels of luminance. The results showed that both dimensions influenced
      bisection performance. Whereas numbers (Experiment 1) induced a systematic shift
      of the subjective midpoint toward the larger digit, luminance (Experiment 2)
      modulated the bisection performance toward the darker flanker. By combining these
      two illusions (Experiments 3 and 4), the two dimensions interfered with each
      other. This pattern of results suggests overlapping representations for physical
      and numerical magnitudes and highlights the value of illusory effects in
      cognitive research.

PMID- 22477060
TI  - Investigations on photoinduced interaction of 9-aminoacridine with certain
      catechols and rutin.
AB  - The fluorescence quenching of 9-aminoacridine by certain biologically important
      catechols and rutin was investigated using absorption, steady state and time
      resolved fluorescence measurements. The in vitro-antioxidant activities of the
      above compounds were studied using deoxyribose degradation assay and nitric oxide
      scavenging assay. The experimental results showed that the fluorescence of 9
      aminoacridine was quenched by quencher molecules via forming ground state
      complex. The bimolecular quenching rate constant k(q), binding constant (K) and
      number of binding sites (n) were calculated at different temperatures from
      relevant fluorescence data. Static quenching mechanism was supported by lifetime
      measurement. The free energy change (DeltaG(et)) for electron transfer process
      was calculated by Rehm-Weller equation. The binding distance of 4-nitrocatechol
      with 9-aminoacridine was obtained according to Forster's non-radiative energy
      transfer theory. Nature of binding forces and their interactions was probed based
      on thermodynamic parameters.

PMID- 22477062
TI  - Simultaneous quantitative analysis of three compounds using three-dimensional
      fluorescence spectra based on digital image techniques.
AB  - Digital image processing has been applied on various fields such as
      classification and qualitative analysis. In this work, a very simple quantitative
      approach was proposed for the first time. Based on the digital grayscale images
      of three-dimensional fluorescence spectra, several wavelet moment invariants were
      calculated, and used to establish the linear models for the quantitative
      analysis. This approach was applied to the quantitative analysis of Tryptophan,
      Tyrosine and Phenylalanine in mixture samples, and the correlation coefficients
      R(2) of the obtained linear models were more than 0.99, which were supported by
      the strict statistical parameters as well as leave-one-out and Jackknife cross
      validations. Our study indicates that the selected wavelet moment invariants are
      immune from the noise and background signals, and the quantitative analysis can
      be performed accurately based on the overlapping peaks of compounds in mixture.
      This proposed approach provides a novel pathway for the analysis of three
      dimensional spectra.

PMID- 22477061
TI  - Reduced fluoresceinamine for peroxynitrite quantification in the presence of
      nitric oxide.
AB  - A new fluorescent analytical methodology for the quantification of peroxynitrite
      (ONOO(-)) in the presence of nitric oxide (NO) was developed. The quantification
      of ONOO(-) is based in the oxidation of the non-fluorescent reduced
      fluoresceinamine to a high fluorescent oxidized fluoresceinamine in reaction
      conditions where the interference of NO is minimized. Screening factorial
      experimental designs and optimization Box-Behnken experimental design
      methodologies were used in order to optimize the detection of ONOO(-) in the
      presence of NO. The factors analysed were: reduced fluoresceinamine concentration
      (C( Fl)); cobalt chloride concentration (C(CoCl2)); presence of oxygen (O(2));
      and, the pH (pH). The concentration of sodium hydroxide (C(NaOH)) needed to
      diluted the initially solution of ONOO(-) was also evaluated. An optimum region
      for ONOO(-) quantification where the influence of NO is minimal was identified -
      C(Fl) from 0.50 to 1.56 mM, C(CoCl2) from 0 to 1.252 * 10(-2) M, pH from 6 to 8
      and C(NaOH) 0.10 M. Better results were found in the presence of NO at pH 7.4,
      C(Fl) 0.5 mM, without oxygen, without cobalt chloride and with a previous
      dilution of peroxynitrite solution with C(NaOH) 0.1 M. This methodology shows a
      linear range from 0.25 to 40 MUM with a limit of detection of 0.08 MUM. The
      bioanalytical methodology was successfully applied in the ONOO(-) quantification
      of fortified serum and macrophage samples.

PMID- 22477063
TI  - Fluorometric determination of bopindolol and celiprolol in pharmaceutical
      preparations and biological fluids.
AB  - Two sensitive fluorometric methods were developed for the determination of both
      bopindolol malonate (BOP) and celiprolol HCl (CLP) based on measuring their
      native fluorescence in methanol and acetonitrile, respectively. For BOP, the
      fluorescence was measured at 316 nm after excitation at 278 nm. The proposed
      method was successfully applied to the assay of commercial tablets as well as
      content uniformity testing. For CLP, the fluorescence was enhanced by the
      addition of carboxymethylcellulose solution and measured at 455 nm after
      excitation at 339 nm. The method was successfully applied to the analysis of CLP
      in tablets and biological fluids. In both methods, interference likely to be
      introduced from co-formulated, co-administered, or chemically related drugs was
      studied. The results were statistically compared with those obtained by reference
      methods and were found to be in good agreement.

PMID- 22477064
TI  - Influence of additional ballooning with a dual wire balloon after a rotational
      atherectomy to expand drug-eluting stent for calcified lesions.
AB  - Calcified lesions have been known as a cause of stent underexpansion which
      increases the risk of thrombosis and in-stent restenosis. A dual wire balloon has
      been introduced to create a focal stress pattern in a localized region of the
      calcification. We evaluated the combination therapy using a dual wire balloon
      after rotational atherectomy (RA) for heavily calcified lesions. Of 21
      consecutive patients with severe calcified lesions, 10 patients were treated with
      a dual wire balloon after RA, and 11 patients were treated with RA alone or, RA
      plus the conventional balloon. Finally, drugeluting stents (DES) were implanted
      in all cases. Baseline characteristics, lesion characteristics, and
      postdilatation procedures were not different between two groups. Before
      implantation of DES, a dual wire balloon enabled adequate dilatation with
      significantly more cracks than RA (1.8 +/- 0.4 cracks vs. 1.2 +/- 0.6 cracks, P =
      0.02). The minimal stent cross sectional area (CSA) and the stent expansion ratio
      were similar in both groups. However, the symmetrical expansion was significantly
      accomplished in patients with a dual wire balloon compared to those without it
      (mean ratio calculated by dividing the shortest diameter by the longest diameter
      at the site of the minimal stent CSA was 0.83 +/- 0.05 vs. 0.76 +/- 0.07, P =
      0.02). Moreover, no in-stent restenosis was observed in patients treated with a
      dual wire balloon at follow-up. In conclusion, by using a dual wire balloon after
      RA, adequate stent expansion and follow-up results were accomplished. This
      combination therapy is safety and feasible procedure for the treatment of severe
      calcified lesions.

PMID- 22477065
TI  - Effects of prolonged exercise on agouti-related protein: a pilot study.
AB  - Agouti-related protein (AgRP), is a signaling peptide that affects feeding
      behavior, energy homeostasis, and has also been shown to stimulate the
      hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine
      the effects of 90 min of treadmill exercise on circulating AgRP concentrations
      and the relationship of AgRP responses to cortisol. Seven young males completed a
      preliminary trial followed by counterbalanced experimental and control trials 4-5
      weeks apart. The experimental trial began 2.5 h after consumption of a standard
      nutrient beverage and consisted of treadmill exercise at 60 % of previously
      determined VO(2max) for 90 min. Blood samples were collected before (-30 and 0
      min), during (18, 36, 54, 72, and 90 min), and following exercise (20, 40, and 60
      min). Blood samples were collected in a resting, control trial at the same time
      points as the experimental trial. Plasma lactate was significantly higher in the
      exercise than the control trial. Although AgRP increased from 18 min of exercise
      to peak at 90 min, these increases were not significantly different than values
      in the control trial. Cortisol responses during the exercise trial were
      significantly higher than the control trial. AgRP concentrations during early
      exercise were positively correlated with cortisol levels later in recovery. The
      obtained data suggest that AgRP concentrations during prolonged steady-state
      exercise are associated with subsequent cortisol increases, but further study is
      required to determine whether there is a causal effect.

PMID- 22477066
TI  - A heavy snorer with multiple prolonged asystoles during the night-reversal by
      CPAP therapy.

PMID- 22477067
TI  - Reversine, a 2,6-disubstituted purine, as an anti-cancer agent in differentiated
      and undifferentiated thyroid cancer cells.
AB  - PURPOSE: A novel and effective treatment is urgently needed to deal with the
      current treatment dilemma in incurable differentiated thyroid cancer (DTC),
      poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC).
      Reversine, a small synthetic purine analogue (2,6-disubstituted purine), has been
      shown to be effective in tumor suppression. METHODS: We performed in vitro
      evaluation of anti-tumor effects of reversine on proliferation, cell cycle, and
      apoptosis in human PDTC, ATC, and follicular thyroid cancer cell lines,
      respectively. RESULTS: Treatment of these three lines with reversine inhibited
      proliferation in a time- and dose-dependent manner. G2/M accumulation was
      demonstrated in cell cycle analysis. Reversine induced apoptosis in PDTC cells
      with caspase-3 and caspase-8 activation, but not caspase-9. Use of a pan-caspase
      inhibitor before treatment with reversine attenuated cell death. Reversine also
      showed in vivo growth inhibitory effects on ATC cells in a xenograft nude mice
      model. CONCLUSIONS: Data demonstrated that reversine is effective in inhibiting
      the growth of thyroid cancer cells by cell cycle arrest or apoptosis, especially
      with the more aggressive ATC and PDTC. Apoptosis was induced by the mitochondria
      independent pathway. Reversine is therefore worthy of further investigation in
      clinical therapeutics.

PMID- 22477068
TI  - Structure and function of purified monoclonal antibody dimers induced by
      different stress conditions.
AB  - PURPOSE: To investigate structure and function of different monoclonal antibody
      (MAb) dimers. METHODS: MAb dimers were induced by process-related, low pH and UV
      light stress. Dimers were isolated and purified by chromatography and extensively
      characterized by biochemical, structural and functional methods. RESULTS: Highly
      purified dimer forms were obtained which enabled detailed characterization.
      Dimers induced by process stress were associated by a single non-covalent
      interaction site between two Fab domains in a characteristic "bone-like"
      structure observed in Transmission Electron Microscopy (TEM). These dimers showed
      reduced potency and antigen binding affinity. Low pH stress generated more stable
      but also non-covalently associated dimers without chemical alterations in a
      typical "closed" conformation according to TEM. These dimer species were more
      compact and more hydrophobic as dimers induced by process stress. They showed
      bioactivity and antigen binding affinity similar to the native monomer. Light
      induced dimers, exhibiting various different conformations, were the most stable
      dimers with various chemical modifications leading to a broad range in size,
      charge and hydrophobicity. These dimers fully lost bioactivity and antigen
      binding affinity. CONCLUSION: The use of highly purified MAb dimers and a panel
      of characterizations methods enabled to obtain a clear picture about molecular
      architecture and function of dimers.

PMID- 22477069
TI  - Combining cheminformatics methods and pathway analysis to identify molecules with
      whole-cell activity against Mycobacterium tuberculosis.
AB  - PURPOSE: New strategies for developing inhibitors of Mycobacterium tuberculosis
      (Mtb) are required in order to identify the next generation of tuberculosis (TB)
      drugs. Our approach leverages the integration of intensive data mining and
      curation and computational approaches, including cheminformatics combined with
      bioinformatics, to suggest biological targets and their small molecule
      modulators. METHODS: We now describe an approach that uses the TBCyc pathway and
      genome database, the Collaborative Drug Discovery database of molecules with
      activity against Mtb and their associated targets, a 3D pharmacophore approach
      and Bayesian models of TB activity in order to select pathways and metabolites
      and ultimately prioritize molecules that may be acting as substrate mimics and
      exhibit activity against TB. RESULTS: In this study we combined the TB
      cheminformatics and pathways databases that enabled us to computationally search
      >80,000 vendor available molecules and ultimately test 23 compounds in vitro that
      resulted in two compounds (N-(2-furylmethyl)-N'-[(5-nitro-3
      thienyl)carbonyl]thiourea and N-[(5-nitro-3-thienyl)carbonyl]-N'-(2
      thienylmethyl)thiourea) proposed as mimics of D-fructose 1,6 bisphosphate, (MIC
      of 20 and 40 MUg/ml, respectively). CONCLUSION: This is a simple yet novel
      approach that has the potential to identify inhibitors of bacterial growth as
      illustrated by compounds identified in this study that have activity against Mtb.

PMID- 22477070
TI  - The effect of engineered mannitol-lactose mixture on dry powder inhaler
      performance.
AB  - PURPOSE: To co-crystallise mannitol and lactose with a view to obtaining crystals
      with more favourable morphological features than either lactose or mannitol
      alone, suitable for use as carriers in formulations for dry powder inhalers
      (DPIs) using simultaneous engineering of lactose-mannitol mixtures. METHODS:
      Mannitol and lactose individually and the two sugars with three different ratios
      were crystallised/co-crystallised using anti-solvent precipitation technique.
      Obtained crystals were sieved to separate 63-90 MUm size fractions and then
      characterised by size, shape, density and in vitro aerosolisation performance.
      Solid state of crystallized samples was studied using FT-IR, XRPD and DSC.
      RESULTS: At unequal ratios of mannitol to lactose, the elongated shape dominated
      in the crystallisation process. However, lactose exerted an opposite effect to
      that of mannitol by reducing elongation ratio and increasing the crystals' width
      and thickness. Crystallised beta-lactose showed different anomers compared to
      commercial lactose (alpha-lactose monohydrate). Crystallised alpha-mannitol
      showed different polymorphic form compared to commercial mannitol (beta
      mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding
      to alpha-mannitol, alpha-lactose monohydrate, beta-lactose, 5alpha-/3beta-lactose
      and 4alpha-/1beta-lactose. In vitro deposition assessments showed that
      crystallised carriers produced more efficient delivery of salbutamol sulphate
      compared to formulations containing commercial grade carriers. CONCLUSION: The
      simultaneous crystallization of lactose-mannitol can be used as a new approach to
      improve the performance of DPI formulations.

PMID- 22477071
TI  - Galactose decorated acid-labile nanoparticles encapsulating quantum dots for
      enhanced cellular uptake and subcellular localization.
AB  - PURPOSE: Biodegradable polymers containing acid-labile segments and galactose
      grafts were formulated into nanoparticles in current study, and enhanced cellular
      uptake and subcellular distribution were clarified. METHODS: Quantum dots (QDs)
      was utilized as an imaging agent and a model of bioactive substances, and
      entrapped into nanoparticles of around 200 nm through a nanoprecipitation
      process. RESULTS: The acid-labile characteristics of QDs-loaded nanoparticles
      were approved by the hemolysis capability, the degradation behaviors of matrix
      polymers, and the fluorescence decay of entrapped QDs after incubation into
      buffer solutions of different pH values. The galactose grafts increased the acid
      lability, due to the hydrophilic moieties on the acid-labile segments, and
      enhanced uptake efficiency of over 50 % was found after 4 h incubation with HepG2
      cells, due to the galactose-receptor mediated endocytosis. The acid-lability led
      to an efficient endosomal escape of QDs-loaded nanoparticles into cytoplasm.
      CONCLUSIONS: The integration of acid-lability, targeting effect, and full
      biodegradable backbone into nanoparticle matrices constitutes a promising
      platform for intracellular delivery of bioactive substances for disease
      diagnosis, imaging and treatment.

PMID- 22477072
TI  - Microstructural elucidation of self-emulsifying system: effect of chemical
      structure.
AB  - PURPOSE: Self-emulsifying systems (SES) emulsify spontaneously to produce fine
      oil-in-water emulsion when introduced into aqueous phase. The self-emulsification
      process plays an important role during formation of emulsion. The objective of
      current work was to understand and explore the inner structuration of SES through
      controlled hydration and further to study the influence of additive on the same
      which ultimately governs performance of final formulation in terms of droplet
      size. METHODS: Droplet size of final formulations containing structural analogues
      of ibuprofen was determined. Microstructural properties of intermediate hydrated
      regimes of SES were investigated using techniques such as small angle X-ray
      scattering, differential scanning calorimetry and rheology. RESULTS: The current
      work established inverse relationship between droplet size of the formulations
      containing structural analogues of ibuprofen and their Log P values.
      Microstructural analysis of intermediate hydrated regimes of the prepared samples
      showed formation of local lamellar structure. Structural analogues of ibuprofen
      significantly altered microstructure of lamellae which was well correlated with
      the droplet size of final formulations. In vitro drug release study showed
      increase in dissolution rate of lipophillic drugs when formulated as SES.
      CONCLUSION: The current work emphasizes the fact that tailor-made formulations
      can be prepared by controlling the properties of intermediate regimes.

PMID- 22477073
TI  - Imaging the distribution of sodium dodecyl sulfate in skin by confocal Raman and
      infrared microspectroscopy.
AB  - PURPOSE: To image SDS distribution across different skin regions, to compare the
      permeability difference between porcine and human skin, and to evaluate the
      interaction between SDS and skin. METHODS: Full thickness porcine and human skin
      was treated with acyl chain perdeuterated SDS (SDS-d(25)) at room temperature and
      at 34  degrees C for 3, 24 and 40 h. SDS distribution in skin was monitored by
      confocal Raman and IR microspectroscopic imaging. Permeation profiles of SDS
      d(25) in skin were derived from the band intensities of the CD(2) stretching
      vibrations. The interaction between SDS and skin was monitored through the CH(2)
      and CD(2) stretching frequencies and the Amide I and II spectral region. RESULTS:
      SDS-d(25) penetrates both porcine and human skin in a time and temperature
      dependent manner, with slightly higher permeability through the stratum corneum
      (SC) in porcine skin. When SDS permeates into the SC, its chains are more ordered
      compared to SDS micelles. The secondary structure of keratin in the SC is not
      affected by SDS-d(25). CONCLUSION: The spatial distribution of SDS-d(25) in skin
      was obtained for the first time. Infrared microscopic imaging provides unique
      opportunities to measure concentration profiles of exogenous materials in skin
      and offers insights to interaction between permeants and skin.

PMID- 22477075
TI  - Verbal responses to past events: Intraverbal relations, or tacts to private
      events?
AB  - Seventy-five undergraduate students worked through a computer program which
      taught them to correctly identify four solid geometry figures. The video screen
      background color was incidently different for each figure. Later, when given a
      colorless background, students were asked to say what color accompanied the
      instructional frames for each superimposed figure. Taken as a whole, the 75
      students correctly recalled the previously paired colors 53% of the time
      (p<.0001) when compared to a random probability of 25% (a replication of the
      experiment produced similar results). Results showed great variability from one
      student to another in the ability to recall colors but scores did not correlate
      with gender or performance in the course. Successful responding to "absent"
      colors was assumed to be the product of multiple variables, among these being the
      possibilities of conditioned seeing and intraverbal relations acquired prior to
      and during the tutorial.

PMID- 22477074
TI  - Bioreducible crosslinked polyelectrolyte complexes for MMP-2 siRNA delivery into
      human vascular smooth muscle cells.
AB  - PURPOSE: Bioreducible crosslinked polyplexes were prepared via disulfide bond
      formation after siRNA condensation with polyethylenimine-modified by deoxycholic
      acid (PEI-DA) to stabilize polyplex structure in an extracellular environment and
      to promote transfection efficiency in human smooth muscle cells (hSMCs). METHODS:
      The PEI-DA/siRNA polyplexes were further modified by crosslinking the primary
      amines of PEI with thiol-cleavable crosslinkers. The effect of disulfide
      crosslinked PEI-DA/siRNA (Cr PEI-DA/siRNA) polyplexes on target gene silencing
      was investigated by transfecting hSMCs with matrix metalloproteinase-2 (MMP-2)
      siRNA under serum conditions. The MMP-2 levels in the conditioned medium were
      examined using gelatin zymography. RESULTS: The Cr PEI-DA/siRNA polyplexes showed
      increased stability against heparin exchange reactions, while their disulfide
      linkages were successfully cleaved under reducing conditions. The polyplex
      crosslinking reaction led to a slight decrease in MMP-2 gene silencing activity
      in hSMCs due to the insufficient redox potential. However, the gene silencing
      efficiency of the Cr PEI-DA/siRNA polypexes was gradually improved in response to
      increasing intracellular reduction potential. The increased serum stability of
      the Cr PEI-DA/siRNA polyplexes resulted in significant enhancement of the
      intracellular delivery efficiency especially under serum conditions. CONCLUSION:
      The Cr PEI-DA/siRNA polyplex formulation may be a promising siRNA delivery system
      for the treatment of incurable genetic disorders.

PMID- 22477076
TI  - Teaching intraverbal behavior to preschool children.
AB  - Four preschool children who were taught to tact a set of Peabody picture cards
      were unable to emit those same responses under intraverbal conditions. A transfer
      of stimulus control procedure was used to bring the responses under intraverbal
      control. A multiple probe design was used to demonstrate experimental control.
      The results indicate that the transfer procedure was effective in developing the
      responses as intraverbals, and in increasing the subjects' scores on the Verbal
      Fluency subtest of the McCarthy Scales. A second study demonstrated that teaching
      four additional subjects to tact both the items and the class of which the items
      were members resulted in the untrained emergence of a few intraverbal responses
      for two of four subjects. For the other subjects and classes, it was still
      necessary to teach each of the responses as intraverbals, further demonstrating
      that tacts and intraverbals are separate verbal operants. The implications of
      these results for the use of Skinner's (1957) analysis of verbal behavior for
      studying typical language development are discussed.

PMID- 22477077
TI  - A functional analysis of verbal delay in preschool children: Implications for
      prevention and total recovery.
AB  - Delays in acquiring age-appropriate verbal repertoires in preschool children with
      no known organic etiology may be explained by defective or absent behavior
      environmental contingencies. This paper presents six possible behavioral
      paradigms that describe verbal episodes between parents and their preschool
      children and how these interactions may inhibit or prevent the acquisition of
      verbal behavior. These paradigms are contrasted with parent-child interactions
      that typically result in age-appropriate verbal repertoires. Identifying the
      reinforcement contingencies that produce delays in acquisition of verbal behavior
      could lead to the development of more effective behavioral programs for
      remediating nonorganic language delay. Recommendations for prevention, treatment
      and total recovery from functional verbal delay and associated mental retardation
      are presented. The relation between contingency-shaped and rule-governed behavior
      in the shaping of verbal behavior is discussed.

PMID- 22477078
TI  - Stimulus control analysis of language disorders: A study of substitution between
      voiced and unvoiced consonants.
AB  - This study attempted to analyze defective stimulus control relations underlying
      persistent substitution between voiced and unvoiced consonants in the speech and
      writing of two children. A series of 20 tests was administered repeatedly. Some
      tests consisted of matching-to-sample tasks, with dictated words, printed words,
      or pictures as samples. Comparison stimuli were arranged in pairs of printed
      words or pictures, such that the only difference in their corresponding spoken
      words was the voicing of one consonant phoneme. In other tests, a stimulus
      (dictated word, printed word, or picture) was presented, and the subject was
      required to emit an oral response (repeat the dictated word, read the printed
      word, or name the picture) or a written response (write to dictation, copy the
      word, or write a picture name). Other tests required the subjects to make a
      same/different distinction in pairs of dictated words that did or did not differ
      in the voicing of a single phoneme. Results showed distinct deficit profiles for
      each subject, consisting of patterns of defective stimulus control relations. The
      subjects were able, however, to distinguish between voiced and unvoiced sounds
      and to produce these sounds.

PMID- 22477079
TI  - Behavioral pharmacology and verbal behavior: Diazepam effects on verbal self
      reports.
AB  - Diazepam (10 mg) was administered to two men performing a delayed matching-to
      sample task in which the number of elements in a compound sample stimulus (one of
      which appeared among 4 comparison stimuli) was manipulated from 1 to 3. After
      each trial, subjects pressed either a "Yes" or "No" button in response to a
      computer-presented query about whether the last choice met a point contingency
      requiring selection of the matching comparison stimulus within a time limit.
      Diazepam simultaneously produced marginal decreases in matching-to-sample
      performance and more pronounced decreases in the accuracy of self-reports about
      the same performance. Diazepam selectively increased false reports of success;
      false reports of failure were not systematically affected. A signal-detection
      analysis summarized these patterns as a decrease in self-report discriminability
      (A') with no systematic change in bias (B'(H)). These preliminary results
      converge with those of clinical lore and the results of studies with other
      benzodiazepine drugs in suggesting that diazepam can produce an "overconfidence"
      in performance self-evaluation, the mechanisms and parameters of which remain to
      be identified. The results were inconsistent with those of one previous study of
      diazepam's effects on performance self-evaluation, but given procedural
      differences between the two studies, the discrepancy may reflect the functional
      independence of verbal operant classes in Skinner's (1957) taxonomy.

PMID- 22477080
TI  - The concept of strength in the analysis of verbal behavior.
AB  - A textual analysis of the concept of strength is presented, based on patterns of
      its occurrence in the book Verbal Behavior (Skinner, 1957). A manual count was
      conducted of all instances of the word "strength," and closely related forms.
      Rates were then plotted and interpreted as revealing the kinds of situations
      where strength is most relevant. Strength appears to be most relevant (as
      measured by instances per page of text) whenever a detailed behavioral analysis
      involves 1) more than one source of strength for a response, 2) multiple
      responses or fragments being strengthened by one or more variables, 3) dynamic
      changes in behavior, or 4) behavior which is not currently or readily observed.
      Further research is needed to evaluate how textual analysis of this sort
      contributes to a science of behavior.

PMID- 22477081
TI  - Mutual exclusivity and exclusion: Converging evidence from two contrasting
      traditions.
AB  - Mutual exclusivity and exclusion are two terms used by cognitive psychologists
      and behavior analysts, respectively, to identify essentially the same phenomenon.
      While cognitive psychologists view mutual exclusivity in terms of a hypothesis
      that individuals use intuitively while acquiring language, behavior analysts
      regard exclusion as a derived stimulus relation that bears upon the acquisition
      and elaboration of verbal behavior. Each research tradition, though at odds with
      respect to accounting for the phenomenon, employs similar procedures to answer
      comparable questions. Insofar as both cognitive and behavioral psychologists are
      studying the same phenomenon, the ground work is established for collaboration
      between them.

PMID- 22477082
TI  - Comments on Skinner's grammar.
AB  - The strong tradition of "school room" grammars may have had a negative influence
      on the reception given a functional analysis of verbal behavior, both within and
      without the field of behavior analysis. Some of the failings of those traditional
      grammars, and their largely prescriptive nature were outlined through reference
      to other critics, and conflicting views. Skinner's own treatment of grammatical
      issues was presented, emphasizing his view of a functional unit and his use of
      the autoclitic and intraverbal functions to describe alternatives to a formal or
      structural analysis. Finally, the relevance of stimulus control variables to some
      recurring questions about verbal behavior and, specifically grammar, were
      mentioned.

PMID- 22477083
TI  - Facilitator control as automatic behavior: A verbal behavior analysis.
AB  - Several studies of facilitated communication have demonstrated that the
      facilitators were controlling and directing the typing, although they appeared to
      be unaware of doing so. Such results shift the focus of analysis to the
      facilitator's behavior and raise questions regarding the controlling variables
      for that behavior. This paper analyzes facilitator behavior as an instance of
      automatic verbal behavior, from the perspective of Skinner's (1957) book Verbal
      Behavior. Verbal behavior is automatic when the speaker or writer is not
      stimulated by the behavior at the time of emission, the behavior is not edited,
      the products of behavior differ from what the person would produce normally, and
      the behavior is attributed to an outside source. All of these characteristics
      appear to be present in facilitator behavior. Other variables seem to account for
      the thematic content of the typed messages. These variables also are discussed.

PMID- 22477084
TI  - Selecting a response form for nonverbal persons: Facilitated communication,
      pointing systems, or sign language?
AB  - The three major types of augmentative communication for nonverbal persons consist
      of writing (or typing), pointing, and signing. These alternative response forms
      are examined in terms of their advantages and disadvantages for establishing
      effective verbal behavior. In addition, these systems are examined using the
      concepts from Skinner's (1957) analysis of verbal behavior (i.e., mand, tact,
      intraverbal, and autoclitic). The results of this analysis show that sign
      language has the most advantages and the fewest disadvantages, and more closely
      parallels speech in terms of the verbal operants. Although, the current trend is
      to favor facilitated communication (typing) and pointing systems, both of these
      response forms have several disadvantages that impede the development of the
      verbal operants. It is suggested that for many nonverbal individuals sign
      language is a better alternative response form, and has a better chance of
      improving speech.

PMID- 22477085
TI  - Teaching topography-based and selection-based verbal behavior to developmentally
      disabled individuals: Some considerations.
AB  - Augmentative and alternative communication systems are widely recommended for
      nonvocal developmentally disabled individuals, with selection-based systems
      becoming increasingly popular. However, theoretical and experimental evidence
      suggests that topography-based communication systems are easier to learn. This
      paper discusses research relevant to the ease of acquisition of topography-based
      and selection-based systems. Additionally, current practices for choosing and
      designing communication systems are reviewed in order to investigate the extent
      to which links have been made with available theoretical and experimental
      knowledge. A stimulus equivalence model is proposed as a clearer direction for
      practitioners to follow when planning a communication training program.
      Suggestions for future research are also offered.

PMID- 22477086
TI  - Mapping the risk of yellow Fever infection.
AB  - The World Health Organization coordinated a comprehensive, systematic review of
      the countries and areas at risk for yellow fever (YF) virus transmission. The
      review applied the following evidence to each country and area considered: human
      and non-human YF cases, human serology for anti-YF antibody obtained prior to
      widespread YF vaccination, altitude, vegetation, and vector distribution. The
      result was the categorization of countries or areas as endemic, transitional, low
      potential for infection, or no risk. This information was adapted to create a map
      that defined the areas where vaccination against YF may be recommended. Travel
      health professionals, countries, and public health bodies can use this
      information as they determine recommendations and requirements for vaccination.
      This paper reviews the process and outcomes of the review of YF risk, and places
      it in the context of providing YF vaccination.

PMID- 22477087
TI  - Pneumonia Due to Drug-Resistant Streptococcus pneumoniae.
AB  - Pneumonia is a major infectious disease associated with significant morbidity and
      mortality, with Streptococcus pneumoniae the predominant pathogen in community
      acquired cases, accounting for 20% to 50% of bacterial cases. Although
      pneumococcal resistance to beta-lactams is now common worldwide, high-dose
      parental penicillin G, many other parental beta-lactams and some oral beta
      lactams continue to be efficacious. The new Clinical and Laboratory Standards
      Institute susceptibility breakpoints for parental penicillin G for nonmeningeal
      infections (<=2 MUg/mL, susceptible; 4 MUg/mL, intermediate; >=8 MUg/mL,
      resistant) introduced in 2008 facilitate appropriate reporting and use of
      penicillin G. Pneumococcal vaccine usage in children from 2000 has led to
      significant decreases in morbidity and mortality due to S. pneumoniae in all age
      groups, and the increase in resistant serotypes, such as 19A, appears to be
      decreasing following the introduction of an expanded valence vaccine in 2010.
      Judicious use of antimicrobial agents is the best long-term approach in order to
      reduce S. pneumoniae resistance.

PMID- 22477088
TI  - Neural and behavioral endophenotypes in ADHD.
AB  - In recent years, descriptive symptom-based approaches of attention deficit
      hyperactivity disorder (ADHD) have been increasingly replaced by more
      sophisticated endophenotype-based strategies, better suited to investigate its
      pathophysiological basis, which is inherently heterogeneous. Measurements derived
      from neuroimaging techniques such as positron emission tomography (PET) and
      magnetic resonance imaging (MRI) constitute endophenotypes of growing interest,
      capable of providing unprecedented windows on neurochemical and neuroanatomical
      components of psychiatric conditions. This chapter reviews the current state of
      knowledge regarding putative neural and behavioral endophenotypes of ADHD, across
      the lifespan. To this end, recent evidence drawn from molecular and structural
      neuroimaging studies are discussed in the light of widely accepted
      neuropsychological and pharmacological models of ADHD.

PMID- 22477089
TI  - How not to think: medical ethics as negative education.
AB  - An implicit rationale for ethics in medical schools is that there is a perceived
      need to teach students how not to think and how not to act, if they are to avoid
      a lawsuit or being struck off by the GMC. However, the imperative to keep within
      the law and professional guidance focuses attention on risks to patients that can
      land a doctor in trouble, rather than what it means to treat a patient humanely
      or well. In this paper I explore the gap between learning how not to think and
      act as a doctor, and learning to be reflective and responsive to patients as
      fellow human beings. This gap is exposed by the difference between a GMC web
      resource for doctors, and a detailed ethical discussion by Gawande in his book
      Complications. The latter raises fundamental questions of meaning, and
      exemplifies an approach to ethical thinking as the appropriate management of
      doubt that, according to the argument of this paper, is of utmost importance for
      doctors.

PMID- 22477090
TI  - Subject to empowerment: the constitution of power in an educational program for
      health professionals.
AB  - Empowerment and user participation represents an ideal of power with a strong
      position in the health sector. In this article we use text analysis to
      investigate notions of power in a program plan for health workers focusing on
      empowerment. Issues addressed include: How are relationships of power between
      users and helpers described in the program plan? Which notions of user
      participation are embedded in the plan? The analysis is based on Foucault's idea
      that power which is made subject to attempts of redistribution will re-emerge in
      other forms. How this happens, and with what consequences, is our analytical
      concern. The analysis is contrasted with 'snapshots' from everyday life in a
      nursing home. The program plan communicates empowerment as a democracy-building
      instrument that the users need. It is a tool for providing expert assistance to
      the user's self-help. User participation is made into a tool which is external to
      the user him-/herself. Furthermore, the analysis shows that the plan's image of
      empowerment presupposes an 'elite user' able to articulate personal needs and
      desires. This is not very applicable to the most vulnerable user groups, who
      thereby may end up in an even weaker position. By way of conclusion, we argue
      that an exchange of undesirable dominating paternalism for a desirable
      empowerment will not abolish power, but may result in more covert and subtle
      forms of power that are less open to criticism. The paper offers insights that
      will facilitate reflections on the premises for practising empowerment-oriented
      health care.

PMID- 22477091
TI  - (1)H, (13)C, (15)N backbone and side-chain resonance assignments of rat
      angiogenin.
AB  - Angiogenin is an unusual member of the pancreatic ribonuclease superfamily that
      induces formation of new blood vessels and is a promising anti-cancer target.
      Here we report backbone and side chain (1)H, (13)C, and (15)N resonance
      assignments for rat angiogenin (residues 24-145), excluding the N-terminal signal
      peptide. These data allow nuclear magnetic resonance structure and inhibitor
      binding studies with the aim of providing angiogenin antagonists as potential
      therapeutics.

PMID- 22477092
TI  - Backbone resonance assignments for the cytoplasmic region of the Mg(2+)
      transporter MgtE in the Mg (2+)-unbound state.
AB  - Magnesium ion (Mg(2+)) is an essential metal element for life, and has many
      cellular functions, including ATP utilization, activation of enzymes, and
      maintenance of genomic stability. The intracellular Mg(2+) concentration is
      regulated by a class of transmembrane proteins, called Mg(2+) transporters. One
      of the prokaryotic Mg(2+) transporters, MgtE, is a 450-residue protein, and
      functions as a dimer. We previously reported that MgtE exhibits the channel-like
      electrophysiological property, i.e., it permeates Mg(2+) according to the
      electrochemical potential of Mg(2+). The Mg(2+)-permeation pathway opens in
      response to the decrease of the intracellular Mg(2+) concentration, while it is
      completely closed at the intracellular Mg(2+) concentration of 10 mM. The crystal
      structures of the MgtE dimer revealed that the Mg(2+)-sensing cytoplasmic region
      consists of the N and CBS domains. The Mg(2+)-bound state of MgtE adopts a
      compact, globular conformation, which is stabilized by the coordination of a
      number of Mg(2+) ions between these domains. On the other hand, in the Mg(2+)
      unbound state, these domains are far apart, and fixed by the crystal packing.
      Therefore, structural analyses in solution were awaited, in order to characterize
      the Mg(2+)-dependent alteration of the MgtE structure and dynamics relevant to
      its gating. In this paper, we report the backbone resonance assignments of the
      dimer of the cytoplasmic region of the MgtE from Thermus thermophilus with a
      molecular weight of 60 KDa, in the Mg(2+)-unbound state.

PMID- 22477093
TI  - Incidence and management of epithelial loosening after LASIK.
AB  - To determine the incidence of recurrent epithelial loosening (REL) following
      laser in situ keratomileusis (LASIK) and evaluate the efficacy of anterior
      stromal micropuncture (ASP) and the application of bandage contact lenses (BCLs)
      in the management of REL after LASIK. A retrospective study including all
      individuals who underwent LASIK with a microkeratome between January 2006 and
      January 2007. Medical records were reviewed to identify patients who were
      diagnosed as having epithelial loosening with or without epithelial defects. Data
      were collected on 5,566 eyes that underwent LASIK with a microkeratome. Eight
      eyes (0.14 % or one in 696 eyes) of seven patients had REL with or without
      epithelial defects. Frequent lubrication, BCL application, and ASP were needed
      for four eyes (50 %) in the management of REL, respectively. All patients
      remained free of symptoms after completion of ASP. REL following LASIK is
      uncommon. Follow-up of patients showed that BCL application and ASP were
      effective in the management of REL following LASIK.

PMID- 22477094
TI  - Generalized instructional control and the production of broadly applicable
      relational responding.
AB  - Two experiments examined the performance of preschool children in tasks requiring
      the generalized matching of faces to faces and names to faces under the control
      of instructional stimuli (background color) that specified the basis by which
      faces were to be matched on a given trial. The children first learned to recite
      all the names, and to select all the faces, in a fixed order (the forward order).
      They then learned to select the faces in response to their spoken names. When the
      faces appeared on a white background, subjects selected the face named. On a gray
      background, they selected the face whose name was next forward. Subsequently,
      over a series of tests, when subjects were presented with novel, but similar
      stimuli with the same names, and with completely novel stimuli with novel names,
      control by the white and gray background colors generalized. In the second
      experiment, on trials with the gray background, when the face bearing the next
      forward relation was not present, the children learned to select an appropriate
      substitute (two faces forward). This performance also generalized to novel
      stimuli. Together with earlier findings, these data suggest that widely
      generalized relational matching performances may arise because the labels for
      these relations are generically and metaphorically extended tacts.

PMID- 22477095
TI  - The effects of schedules of reinforcement on instruction-following in human
      subjects with verbal and nonverbal stimuli.
AB  - The experiment reported here represents a partial replication of an experiment by
      Newman, Buffington, and Hemmes (in press) and analyzes responding in college
      students as a function of three different schedules of reinforcement (FR 1, FR 2,
      FR 3) and either verbal discriminative stimuli (instructions) or nonverbal
      discriminative stimuli (different colored cards). All consequences (tokens) were
      based on behavior consistent either with the verbal discriminative stimulus
      (S(D)) or with the nonverbal S(D). The schedule of reinforcement varied across
      subjects, and accuracy of the verbal and nonverbal S(D)s varied across phases
      from. Results showed that the behavior of all continuous reinforcement (FR 1)
      subjects was sensitive to the accuracy of the verbal S(D)s, but the behavior of
      subjects in the nonverbal S(D) conditions showed more sensitivity than the
      behavior of subjects in verbal conditions under intermittent schedules (FR 2 and
      FR 3). These finding suggest that the behavior of subjects in experiments where
      instructions are sometimes pitted against actual contingencies of reinforcement
      is a function not only of the instruction, but also of the type of reinforcement
      schedule used.

PMID- 22477096
TI  - A conceptual analysis of request teaching procedures for individuals with
      severely limited verbal repertoires.
AB  - There have been many published reports of attempts to teach requests to
      individuals with severely limited verbal repertoires associated with
      developmental disabilities. Few of these studies used Skinner's (1975) term mand
      to refer to the behavior taught, yet many seemed to be influenced by Skinner's
      analysis. We analyzed procedures according to three variables: motivational
      conditions, supplemental stimulation, and consequences. Individuals with severely
      limited verbal repertoires provide unique opportunities to study how each of
      these three variables influence the acquisition of requests. Our analysis
      indicated that several different procedures were effective in teaching requests,
      however the degree of supplemental stimulation for the requests varied greatly.
      Future request teaching programs should consider how each of these three
      variables influences targeted responses as well as how these variables influence
      generalization from teaching contexts to nonteaching contexts.

PMID- 22477097
TI  - A review of interventions to teach a mand repertoire.
AB  - Interventions which teach developmentally disabled persons to make requests and
      choices are now widely recommended. Recent changes in general approaches to
      teaching request-making have been noted which are consistent with theory and
      research concerning mands. Three categories of interventions, incidental
      teaching, choice making, and the interrupted behavior chain are also examined
      with regard to theory concerning the mand and establishing operations (EOs).
      Several of the critical features of EOs, and in particular the momentary aspect
      of EOs, have not been well incorporated into interventions. Suggestions for
      improvement of mand interventions are therefore proposed.

PMID- 22477099
TI  - Review of R. A. Harris' linguistics wars.

PMID- 22477098
TI  - An analysis of concept learning: simple conceptual control and definition-based
      conceptual control.
AB  - Concept learning can involve either contingency shaping of stimulus-class
      discriminations or the application of definitions of the concepts. Experimental
      behavior analysts have studied contingency shaping, whereas educational
      psychologists have studied definitional concept training. In this paper, we
      analyze definition-based concept learning in terms of stimulus-response chains.
      Then we apply this chaining analysis to principles of instruction proposed by
      educational psychologists. These principles include (a) stating the definition in
      terms of critical and variable attributes, (b) using examples and nonexamples,
      (c) using a rational set of examples and nonexamples, (d) presenting coordinate
      concepts simultaneously, and (e) presenting the next instance based on the
      learner's previous error.

PMID- 22477100
TI  - Review of Pinker's the language instinct.

PMID- 22477101
TI  - On structure-dependent grammars: a reply to Mabry.
AB  - In a recent paper, Mabry (1993) examines various aspects of Skinner's (1957)
      treatment of grammar, and he compares it with cognitivist approaches. Mabry gives
      convincing reasons for concluding that Skinner's approach is superior. But Mabry
      virtually ignores one of the most important features of grammatical behavior,
      namely, its structure dependence. Since Chomsky's main argument against Skinner's
      treatment of verbal behavior is based on this feature, Mabry's analysis must be
      expanded to include a behavior-analytic treatment of it. Only then can real
      progress be made in bringing cognitivists closer to functional analyses of verbal
      behavior. A brief outline of a behavior-analytic explanation of structure
      dependence is given in the present paper.

PMID- 22477103
TI  - Reminders of secular authority reduce believers' distrust of atheists.
AB  - Atheists have long been distrusted, in part because they do not believe that a
      watchful, judging god monitors their behavior. However, in many parts of the
      world, secular institutions such as police, judges, and courts are also potent
      sources of social monitoring that encourage prosocial behavior. Reminders of such
      secular authority could therefore reduce believers' distrust of atheists. In our
      experiments, participants who watched a video about police effectiveness
      (Experiment 1) or were subtly primed with secular-authority concepts (Experiments
      2-3) expressed less distrust of atheists than did participants who watched a
      control video or were not primed, respectively. We tested three distinct
      alternative explanations for these findings. Compared with control participants,
      participants primed with secular-authority concepts did not exhibit reduced
      general prejudice against out-groups (Experiment 1), prejudice reactions
      associated with functional threats that particular out-groups are perceived to
      pose (specifically, viewing gays with disgust; Experiment 2), or general distrust
      of out-groups (Experiment 3). These findings contribute to theory regarding both
      the psychological bases of prejudices and the psychological functions served by
      gods and governments.

PMID- 22477104
TI  - On near misses and completed tasks: the nature of relief.
AB  - What is the nature and function of relief? Relief has been studied little in
      psychological science despite its familiarity and pervasiveness. Two studies
      revealed that relief can result from two distinct situations: the narrow
      avoidance of an aversive outcome (near-miss relief) and completion of an onerous
      or aversive event (task-completion relief). Study 1 found that recollections of
      near-miss relief were marked by more downward counterfactual thoughts and greater
      feelings of social isolation than recollections of task-completion relief. Study
      2 experimentally elicited the two types of relief and found mediational evidence
      that relief following near misses elicits feelings of social isolation via its
      stimulation of counterfactual thinking. That near-miss relief is characterized by
      counterfactual thinking suggests that it prompts people to contemplate how to
      avert similar experiences in the future, whereas task-completion relief may serve
      to reinforce endurance during difficult tasks.

PMID- 22477105
TI  - Embodied metaphors and creative "acts".
AB  - Creativity is a highly sought-after skill. Prescriptive advice for inspiring
      creativity abounds in the form of metaphors: People are encouraged to "think
      outside the box", to consider a problem "on one hand, then on the other hand",
      and to "put two and two together" to achieve creative breakthroughs. These
      metaphors suggest a connection between concrete bodily experiences and creative
      cognition. Inspired by recent advances in the understanding of body-mind linkages
      in the research on embodied cognition, we explored whether enacting metaphors for
      creativity enhances creative problem solving. Our findings from five studies
      revealed that both physical and psychological embodiment of metaphors for
      creativity promoted convergent thinking and divergent thinking (i.e., fluency,
      flexibility, or originality) in problem solving. Going beyond prior research,
      which focused primarily on the kind of embodiment that primes preexisting
      knowledge, we provide the first evidence that embodiment can also activate
      cognitive processes that facilitate the generation of new ideas and connections.

PMID- 22477106
TI  - Testosterone affects gaze aversion from angry faces outside of conscious
      awareness.
AB  - Throughout vertebrate phylogeny, testosterone has motivated animals to obtain and
      maintain social dominance-a fact suggesting that unconscious primordial brain
      mechanisms are involved in social dominance. In humans, however, the prevailing
      view is that the neocortex is in control of primordial drives, and testosterone
      is thought to promote social dominance via conscious feelings of superiority,
      indefatigability, strength, and anger. Here we show that testosterone
      administration in humans prolongs dominant staring into the eyes of threatening
      faces that are viewed outside of awareness, without affecting consciously
      experienced feelings. These findings reveal that testosterone motivates social
      dominance in humans in much the same ways that it does in other vertebrates:
      involuntarily, automatically, and unconsciously.

PMID- 22477107
TI  - Integrating sexual objectification with object versus person recognition: the
      sexualized-body-inversion hypothesis.

PMID- 22477108
TI  - The role of automatic reinforcement in early language acquisition.
AB  - The vocal behavior of five children was recorded and analyzed during pre- and
      post-pairing conditions. Between these conditions there was a pairing condition
      where a target sound, word, or phrase was paired with an established form of
      reinforcement (e.g., tickling). In the first experiment all of the children
      emitted the targeted responses during the post-pairing condition. The results
      showed that the children acquired new vocal and verbal responses by pairing
      neutral stimuli with established forms of conditioned or unconditioned
      reinforcement. Perhaps the most significant aspect of these results was that new
      vocal responses were acquired by the children without the use of direct
      reinforcement, echoic training, or prompts. In the second experiment several
      parameters of the pairing procedure were examined. The results of the two
      experiments have implications for the analysis of native language acquisition,
      and for the development of language intervention procedures for individuals who
      fail to acquire language.

PMID- 22477109
TI  - Automatic reinforcement and automatic punishment in infant vocal behavior.
AB  - Two female infants, aged 11 and 14 months, were exposed to a procedure in which
      an experimenter-emitted vocal response was paired with an established form of
      reinforcement (positive condition). One of the subjects was also exposed to a
      procedure in which an experimenter-emitted vocal response was paired with a
      neutral stimulus (neutral condition), and a procedure in which an experimenter
      emitted vocal response was paired with a mild aversive stimulus (negative
      condition). An AB design was used with pre- and post-pairing measures. The
      results showed that after the positive pairing the targeted responses increased
      in frequency in 75% of the sessions. Responding remained constant during the
      neutral condition, but dropped sharply in the negative condition. These data
      suggest that a critical variable related to an infant's native language
      acquisition is the stimulus-stimulus pairing process that occurs when parents or
      caretakers speak to their infants.

PMID- 22477110
TI  - Differential latency and selective nondisclosure in verbal self-reports.
AB  - Several previous studies have examined the correspondence between self-reports
      and the delayed identity match-to-sample performance they supposedly described.
      The present two experiments used similar procedures to explore different
      characteristics of the self-reports. In both studies, match-to-sample responses
      were successful (earned points) if they were both correct and faster than a time
      limit. Following each response, a computer-presented query asked whether the
      response had been successful, and subjects replied by pressing a "Yes" or "No"
      button. Experiment 1 analyzed self-report latencies from a previously-published
      study (Critchfield, 1993a). Latencies generally were longer for self-reports of
      failure than for self-reports of success. In Experiment 1, a "Yes" or "No" self
      report was required to advance the session. In Experiment 2, self-reports were
      optional. In addition to "Yes" and "No" buttons, subjects could press a third
      button (a "nondisclosure" option) to remove the self-report query without
      providing a "Yes" or "No" answer. Across a range of conditions, nondisclosures
      always occurred more frequently after match-to-sample failures than after
      successes (i.e., under conditions in which a self-report of failure would be
      appropriate). The effects observed in the two experiments are consistent with a
      history of differential punishment for uncomplimentary self-reports, which casual
      observation and some descriptive studies suggest is a common experience in United
      States culture. The research necessary to explore this notion should produce data
      that are of interest to psychologists both within and outside of Behavior
      Analysis.

PMID- 22477111
TI  - Delayed outcomes and rule-governed behavior among "noncompliant" and "compliant"
      boys: a replication and extension.
AB  - The present research investigated the effects of verbal, contingency-specifying,
      stimuli on compliance among two groups of preschool-aged boys. Experiment 1
      assessed the joint influence of prior compliance history and reinforcement
      parameters on compliance, and Experiment 2 explored the utility of distinguishing
      between the evocative and function-altering effects of verbal stimuli. Results
      from Experiment 1 showed that statements specifying a behavior and an outcome
      controlled similar levels of compliance in "compliant" and "noncompliant" boys
      under conditions of immediate reinforcement, but as the opportunity for
      reinforcement became more delayed (or nonexistent), the performance of
      "noncompliant" boys deteriorated. Results from Experiment 2 showed that
      statements specifying immediate and delayed reinforcers, but not statements
      specifying no reinforcer, controlled high levels of compliance in both compliant
      and noncompliant boys, even after a 15-20 minute delay in the opportunity to
      respond. These results suggest that rules, or contingency specifying stimuli with
      function-altering, rather than evocative effects, reliably control the behavior
      of boys as young as 4 or 5 years-old.

PMID- 22477112
TI  - An experimental analysis of ongoing verbal behavior: reinforcement, verbal
      operants, and superstitious behavior.
AB  - Four adult humans were asked to asked to "find" and talk about a particular topic
      to a person in an adjoining room, and were instructed that they would hear a
      short beep (the only form of reply from the other person) when they were talking
      about the topic, or were "close" to the topic. In Session 1, the experimenter in
      the adjoining room presented the beeps in the manner of shaping, or the
      differential reinforcement of successive approximations, "toward" the designated
      topic. In Session 2, the same conditions were in effect but the experimenter was
      unable to hear the subject and the beeps were presented noncontingently in a way
      that roughly matched the frequency and distribution of presentations in Session
      1. In Session 3, shaping conditions were again in effect but with a different
      topic than that designated for Session 1. Audio recordings were transcribed in a
      way that was designed to show the progress of shaping over time. These and
      additional forms of supporting data and accompanying rationale are presented and
      discussed in detail. Issues raised by the methodology and results of the
      experiment include the nature of the verbal operant, superstitious verbal
      behavior, and a variety of methodological issues relevant to the experimental
      analysis of ongoing or continuous verbal behavior.

PMID- 22477113
TI  - The functional analysis of psychological terms: in defense of a research program.
AB  - In 1945, B. F. Skinner outlined a proposal that psychological or mentalistic
      terms found in natural language might be analyzed empirically in terms of the
      variables, conditions, and contingencies of which they may be observed to be a
      function. Such an analysis would enable discriminations to be made between
      different classes of variables that enter into the control of the term. In this
      way, the analysis would clarify what is traditionally called the "meanings" of
      such terms as they occur as properties of verbal behavior. Despite his expressed
      confidence in the success of such a program, Skinner largely abandoned the
      functional analysis of psychological terms in favor of the development of a
      promising new field; the experimental analysis of behavior. The present paper
      argues that the original program is of great importance as well, and for the
      following reasons: (a) to make full, immediate, and (most importantly) effective
      contact with the range of issues and terms of central importance to the
      traditionally and culturally important concepts of "mind" and "mental life" (and
      thereby demonstrating the relevance of radical behaviorism to the full range of
      human and verbal behavior); and (b) to extend the methodology of the functional
      analysis of verbal behavior more generally. Such a research program would
      demonstrate, through an empirically-based scientific analysis, that the
      philosophical problems concerning "mental life" may be productively analyzed as
      problems of verbal behavior. Issues of methodology are discussed, and possible
      methodological strategies are proposed regarding the confirmation of behavior
      analytic interpretations of mentalistic terms.

PMID- 22477114
TI  - Verbal behavior in the measuring process.
AB  - The behavior called "measuring" generates new stimuli that intraverbally evoke
      new and potentially more effective responding to the situation under
      investigation. The nature of the measurement-produced contribution to these
      supplementary antecedent controls is examined, particularly with respect to
      changes in what can then be said or known. A simple problem (fitting a tablecloth
      to a table) is analyzed with measuring prohibited. Autoclitically related tacts
      are seen to emerge and form statements intraverbally. The conclusion is that only
      when quantitative statements evoked by measurement records supplement the
      statements featuring autoclitically related tacts can a new and more effective
      level of responding occur.

PMID- 22477116
TI  - Editorial.

PMID- 22477117
TI  - Contingency adduction of "symbolic aggression" by pigeons.
AB  - THIS STUDY ADDRESSED THE QUESTION: Can novel social behavior arise even though
      the organism has had no explicit training in that particular social pattern?
      Seven pigeons were trained individually to peck keys for brief access to food.
      Four of these birds were also trained to peck two "switching keys" which, at
      first, raised or lowered the requirements on their own food keys. Later, these
      switching keys no longer affected an animal's own requirements, but raised or
      lowered the requirements imposed on a second pigeon working concurrently for food
      in an adjacent chamber. The second animal was trained only on the food key. In
      each such pair, the pigeon trained on the switching keys reliably pecked
      whichever one raised its partner's schedule-requirements. This novel pattern of
      behavior did not directly benefit the first bird, arose spontaneously as a
      recombination of previously established nonsocial repertoires, and seemed to be
      maintained entirely by its effects on the animal in the adjacent chamber.

PMID- 22477118
TI  - Intraverbal stimulus-response reversibility: Fluency, familiarity effects, and
      implications for stimulus equivalence.
AB  - English-speaking subjects with little knowledge of the French language used a
      computerized flashcard program, Think Fast, to learn 16 English-French word pairs
      (intraverbals) by typing one word of the pair when presented with the other word
      as a textual stimulus. In Phase 1, half of the intraverbals were taught from
      French to English (FE-1) and half from English to French (EF-1). Then, in Phase
      2, training continued with the stimulus and response items of each intraverbal
      reversed, i.e., cards previously in the FE-1 condition were trained from English
      to French (EF-2) and cards previously in the EF-1 condition were trained from
      French to English (FE-2). Feedback was provided throughout the experiment.
      Reversing the stimulus and response items in Phase 2 significantly reduced rate
      correct and accuracy scores for eight of the nine subjects. In Experiments 1 and
      2, this effect was more pronounced for cards in the EF-2 condition; in Experiment
      3, when the criterion for a "correct" response was more lenient, there was no
      consistent difference between cards in the EF-2 and FE-2 conditions. Symmetry, as
      indicated by accuracy scores on the first trial in Phase 2, was generally poor:
      eight of the nine subjects averaged only 29% correct when asked to respond to the
      reversed relations for the first time. We relate our paradigm and results to
      recent developments in fluency, verbal behavior, and stimulus equivalence, and
      provide directions for future research.

PMID- 22477119
TI  - The role of mediating verbal behavior in selection-based responding.
AB  - Michael (1985) distinguished between two kinds of verbal behavior which he
      identified as selection-based (SB) and topography-based (TB). Research has shown
      substantial differences between the two types of verbal behavior for nonverbal
      participants, but little differences has been found with highly verbal
      participants. This study arranged for highly verbal participants (college
      students) to engage in a SB task while "talking aloud," one of Ericsson & Simon's
      (1993) techniques for conducting protocol analyses. The transcripts of these
      sessions were analyzed in terms of Skinner's (1957) elementary verbal operants.
      Very consistent types of statements were found to precede correct selections in
      the SB task. This finding lends support to the possibility that some SB
      conditional discriminations, and related emergent equivalence relations, are
      mediated by TB vocal responding when using highly verbal participants. These data
      also account for some of the differences observed in the SB and TB research.

PMID- 22477120
TI  - Relating equivalence relations to equivalence relations: A relational framing
      model of complex human functioning.
AB  - The current study aimed to develop a behavior-analytic model of analogical
      reasoning. In Experiments 1 and 2 subjects (adults and children) were trained and
      tested for the formation of four, three-member equivalence relations using a
      delayed matching-to-sample procedure. All subjects (Experiments 1 and 2) were
      exposed to tests that examined relations between equivalence and non-equivalence
      relations. For example, on an equivalence-equivalence relation test, the complex
      sample B1/C1 and the two complex comparisons B3/C3 and B3/C4 were used, and on a
      nonequivalence-nonequivalence relation test the complex sample B1/C2 was
      presented with the same two comparisons. All subjects consistently related
      equivalence relations to equivalence relations and nonequivalence relations to
      nonequivalence relations (e.g., picked B3/C3 in the presence of B1/C1 and picked
      B3/C4 in the presence of B1/C2). In Experiment 3, the equivalence responding, the
      equivalence-equivalence responding, and the nonequivalence-nonequivalence
      responding was successfully brought under contextual control. Finally, it was
      shown that the contextual cues could function successfully as comparisons, and
      the complex samples and comparisons could function successfully as contextual
      cues and samples, respectively. These data extend the equivalence paradigm and
      contribute to a behaviour-analytic interpretation of analogical reasoning and
      complex human functioning, in general.

PMID- 22477121
TI  - A review of studies examining the nature of selection-based and topography-based
      verbal behavior.
AB  - Selection-based (SB) verbal behavior, in most general terms, consists of
      selecting stimuli from an array, which presumably has some effect on a listener.
      Topography-based (TB) verbal behavior consists of responses with unique
      topographies (e.g. speaking, signing, writing) which is also presumed to have
      some effect on a listener. This article reviews research examining the nature of
      these two types of verbal behavior. Overall, TB verbal behavior appears to be
      more easily acquired and may also function to mediate some SB verbal behavior.

PMID- 22477123
TI  - Editorial.

PMID- 22477122
TI  - Meeting the enemy: An essay review of Noam Chomsky: A life of dissent by Robert
      F. Barsky.

PMID- 22477124
TI  - The speaker as listener: The interpretation of structural regularities in verbal
      behavior.
AB  - Regularities in word order not specifically addressed by Skinner require
      behavioral interpretation if our field is to become more influential among
      students of language. Three such phenomena are briefly described in traditional
      structural terms and are offered as test cases: subtle differences in dative
      verbs, transformational traces, and the formation of compound nouns. It is argued
      that the variables that control such regularities derive from the speaker's
      repertoire as listener. Intraverbal frames are established as verbal responses in
      the listener through reinforcement by parity. Transitions from element to element
      in such frames are controlled, moment to moment in time, partly by the speaker's
      responses as a listener to his or her own verbal behavior. Although this account
      offers only a tentative interpretation of grammar and syntax in a limited domain,
      it suggests that the conceptual tools of behavior analysis are adequate to the
      task of explaining even the most subtle of grammatical rules.

PMID- 22477125
TI  - Ape language research: A review and behavioral perspective.
AB  - The ape language research of the Gardners, Fouts, Terrace, Rumbaugh, and Savage
      Rumbaugh is reviewed. This research involved the raising of chimpanzees (and a
      bonobo) in human-like environments over extended time periods. The results
      indicate that apes are capable of learning small verbal repertoires in a fashion
      similar to that of human infants. The writings of the ape language researchers
      show an opposition to behavioral approaches to language. Although they
      characterize each other's work as behavioral, they oppose such explanations
      applied to their own work. A behavior-analytic approach to language has much
      empirical support, and behavioral treatments for people with language delays have
      produced substantial results. Despite the protestations of the ape language
      researchers, now is an appropriate time to apply the extensive knowledge base
      derived from a science of behavior to language acquisition in apes.

PMID- 22477127
TI  - Protocol analysis and the "silent dog" method of analyzing the impact of self
      generated rules.
AB  - Within the cognitive literature, verbal protocols of cognitive events are plagued
      by difficult questions of unconsciousness, completeness, reactivity, and
      validity. In this paper we argue that these concerns apply with much less force
      or not at all when protocol analysis is used to determine whether a given
      instance of behavior is governed by self-generated rules. When adequate controls
      are used, some patterns of results allow this question to be answered
      unambiguously and in a manner untouched by the philosophical hurdles encountered
      within the cognitive literature on protocol analysis. We argue that in at least
      some circumstances a slightly modified version of protocol analysis allows us to
      know, in a functional sense, what a person was thinking. Protocol analysis can be
      very useful to behavior analysts who are interested in determining whether task
      relevant behavior is controlled by self-generated rules or is purely contingency
      shaped.

PMID- 22477126
TI  - Protocol analysis as a tool for behavior analysis.
AB  - The study of thinking is made difficult by the fact that many of the relevant
      stimuli and responses are not apparent. Although the use of verbal reports has a
      long history in psychology, it is only recently that Ericsson and Simon's (1993)
      book on verbal reports explicated the conditions under which such reports may be
      reliable and valid. We review some studies in behavior analysis and cognitive
      psychology that have used talk-aloud reporting. We review particular methods for
      collecting reliable and valid verbal reports using the "talk-aloud" method as
      well as discuss alternatives to the talk-aloud procedure that are effective under
      different task conditions, such as the use of reports after completion of very
      rapid task performances. We specifically caution against the practice of asking
      subjects to reflect on the causes of their own behavior and the less frequently
      discussed problems associated with providing inappropriate social stimulation to
      participants during experimental sessions.

PMID- 22477128
TI  - The trouble with babies and the value of bathwater: Complexities in the use of
      verbal reports as data.
AB  - Recent interest among behavior analysts in protocol analysis techniques prompts a
      consideration of some general measurement issues and some special issues relevant
      to protocol analysis. The development of behavior- analytic method and theory
      specific to verbal report research is a good thing, and Ericsson and Simon's
      (1984) book, Protocol Analysis, provides a useful model of integrating
      psychological theory and the craft of research. But protocol analysis techniques
      do not provide a magic window to the "world within the skin," and individual
      researchers should adopt these techniques only after confronting thorny issues
      such as how to determine the operating characteristics of verbal reports about
      private events, how to identify public performances to which protocol analysis
      can be applied productively, and how to maintain theoretical integrity in the
      empirical search for private events. We also caution against letting enthusiasm
      (and controversy) regarding protocol analysis distract behavior analysts from the
      benefits of using verbal report methods to study interesting events that are
      public in principle but difficult to measure in practice.

PMID- 22477129
TI  - Memory as behavior: The importance of acquisition and remembering strategies.
AB  - The study of memory has traditionally been the province of cognitive psychology,
      which has postulated different memory systems that store memory traces to explain
      remembering. Behavioral psychologists have been unsuccessful at empirically
      identifying the behavior that occurs during remembering because so much of it
      occurs rapidly and covertly. In addition, behavior analysts have generally been
      disinterested in studying transient phenomena such as memory. As a result, the
      cognitive interpretation has been the only one that has made and tested useful
      predictions. Recent experimental evidence acquired while having participants
      "think aloud" suggests that a behavioral approach to memory may provide a
      superior account of memory performance and allow applied scientists to observe
      and modify memory-related behavior with well-known applied behavior-analytic
      techniques. We review evidence supporting and extending the interpretation of
      memory provided by Palmer (1991), who described memory in terms of precurrent
      behavior that occurs at the time of acquisition in preparation for problem
      solving that occurs at the time of remembering.

PMID- 22477130
TI  - Current status and future directions of the analysis of verbal behavior:
      Introductory remarks.

PMID- 22477131
TI  - The experimental analysis of verbal behavior.

PMID- 22477132
TI  - Why I stopped reading verbal behavior (and continue to study perceptual control
      theory).

PMID- 22477133
TI  - Interpreting verbal behavior.

PMID- 22477134
TI  - Promoting synthesis in the analysis of verbal relations.

PMID- 22477135
TI  - Computer simulations of verbal behavior for research and persuasion.

PMID- 22477136
TI  - Current status and future directions of operant research on verbal behavior:
      Baselines.

PMID- 22477137
TI  - The methodological challenge of the functional analysis of verbal behavior.

PMID- 22477138
TI  - Something for the future.

PMID- 22477139
TI  - Sentence and sentence structure in the analysis of verbal behavior.

PMID- 22477140
TI  - The verbal operant: Cause and/or effect.

PMID- 22477141
TI  - The analysis of verbal behavior: Where are we?

PMID- 22477142
TI  - Realizing the potential of Skinner's analysis of verbal behavior.

PMID- 22477143
TI  - Verbal behavior: Implications of its mediational and relational characteristics.

PMID- 22477144
TI  - Contributions of verbal behavior to instructional technology.

PMID- 22477145
TI  - The current status and future directions of the analysis of verbal behavior:
      Comments on the comments.

PMID- 22477147
TI  - A deeper analysis of the spacing effect after "deep" encoding.
AB  - The most common encoding strategies used by participants in word list studies
      include rehearsal and using the story mnemonic. Previous studies have suggested
      that with a rote-rehearsal strategy, mixed lists lead people to borrow rehearsal
      time from massed items and to give it to spaced items. Using rehearse-aloud
      methodologies, we demonstrated in Experiment 1 that the borrowing effect does not
      occur in the story mnemonic. However, the rates of rehearsal of individual items
      provided a good prediction of their subsequent recall rates, with spaced items
      being rehearsed more often in both mixed and pure lists. In experiment 2, we
      demonstrated that creating "story links" between items enhanced recall, but it
      did not affect the magnitude of the spacing effect. These results suggest that a
      massed-item deficit in encoding may underlie the spacing effect in the story
      mnemonic.

PMID- 22477146
TI  - Unraveling STIM2 function.
AB  - The discovery of molecular players in capacitative calcium (Ca(2+)) entry, also
      referred to as store-operated Ca(2+) entry (SOCE), supposed a great advance in
      the knowledge of cellular mechanisms of Ca(2+) entry, which are essential for a
      broad range of cellular functions. The identification of STIM1 and STIM2 proteins
      as the sensors of Ca(2+) stored in the endoplasmic reticulum unraveled the
      mechanism by which depletion of intracellular Ca(2+) stores is communicated to
      store-operated Ca(2+) channels located in the plasma membrane, triggering the
      activation of SOCE and intracellular Ca(2+)-dependent signaling cascades. Initial
      studies suggested a dominant function of STIM1 in SOCE and SOCE-dependent
      cellular functions compared to STIM2, especially those that participate in immune
      responses. Consequently, most of the subsequent studies focused on STIM1.
      However, during the last years, STIM2 has been demonstrated to play a more
      relevant and complex function than initially reported, being even important to
      sustain normal life in mice. These studies have led to reconsider the role of
      STIM2 in SOCE and its relevance in cellular physiology. This review is intended
      to summarize and provide an overview of the current data available about this
      exciting isoform, STIM2, and its actual position together with STIM1 in the
      mechanism of SOCE.

PMID- 22477148
TI  - Prenatal genetic testing: an investigation of determining factors affecting the
      decision-making process.
AB  - Despite the increase in popularity of prenatal genetic testing, relatively little
      is known about the role psychological factors play in the decision-making
      process. In this analogue study, a sample of Italian female university students
      was used to investigate determining factors that predict the intention of
      undergoing prenatal genetic testing. Structural Equation Modelling was used to
      describe the dynamic interplay between knowledge, beliefs, attitudes and health
      related behaviour such as prenatal genetic testing. Following the Theory of
      Reasoned Action, three dimensions predicted the intention to undergo prenatal
      genetic testing: the need for more scientific information, a positive attitude
      towards genetic testing, and the inclination to terminate pregnancy after
      receiving a positive test result. Results showed that less religious women tended
      to be more in favour of prenatal tests and in undertaking such tests. This
      preliminary study provides genetic counsellors and policy makers with a clearer
      picture of their clients' motives and attitudes behind the decision-making
      process of prenatal genetic testing, contributing to improving both the
      communication process between counsellors and their clients and the organization
      of genetic services.

PMID- 22477149
TI  - Generation, functional analysis and utility of Citrus grandis EST from a flower
      derived cDNA library.
AB  - Pummelo (Citrus grandis) is one of the most important species found in the genus
      Citrus and one of the ancestors of sweet oranges. We used flower buds at
      different developmental stages to construct the first cDNA library for this
      species. A total of 3,758 EST sequences were generated from the cDNA library and
      clustered into 2,228 unigenes, comprising 451 contigs and 1,777 singletons. Among
      these unigene sequences, 1,266 have significant homology to the non-redundant
      protein database, from which 891 were assigned to one or more gene ontology
      categories. Functional categorization of the annotated unigenes showed that 760
      genes were involved in molecular function, 1,189 in biological processes and
      1,154 in cellular component categorization. Homologs of genes regulating many
      aspects of flower development were also identified, including those for organ
      development, cell-cycle control and cell and tissue differentiation. The majority
      of these genes (e.g., embryo relatives, YABBY-like, MAD Box, SKP-like and SRNAs)
      are the first representatives in Citrus, providing an opportunity to explore the
      cause of self incompatibility and embryo development in Citrus. Patterns of
      transcript accumulation were characterized by real-time qPCR for 13 of these
      genes. Many potential molecular markers were also identified in this EST data
      set; 212 Simple Sequences Repeats (SSRs), 717 transposon elements and 115
      candidate single nucleotide polymorphisms (SNPs) were found. An assessment of a
      set of 212 SSR primer pairs on 16 citrus genotypes showed polymorphism with 122
      (57.82%) markers. Similarly, a set of eight contigs were used to confirm in
      silico predicated SNPs in a set of five genotypes using wet lab experiments,
      three contigs were generated as scorable and sequenceable amplicons and no PCR
      amplicons were obtained from five contigs. The outcome of this study could aid in
      the discovery of genes involved in reproductive developments. Identified
      candidate genes can be experimentally tested for their functions in various
      important processes. SSR, SNP and transposon element-containing data sets may
      facilitate marker development and can be used for citrus molecular breeding,
      linkage map construction, evolutionary, phylogenetic and population genetic
      studies.

PMID- 22477150
TI  - The effects of fever on hormone ghrelins, immunoglobulins, and heat shock protein
      70 expression after swine flu vaccinations.
AB  - For analyzing the changes in immunoglobulins, HSP70, ghrelin levels in blood
      samples were collected from volunteers vaccinated against swine flu before the
      vaccinations and on days 3, and 15, and 1 and 2 months after the vaccination in
      the presence or absence of fever associated with the it. The study included 11
      subjects having developed a fever, and 13 subjects not having a fever, and 20
      control subjects. Immunoglobulins were measured by nephelometry, and HSP70 and
      ghrelins by appropriate ELISA tests. The level of ghrelin was reduced, while the
      level of HSP70 was significantly increased in subjects who developed fevers. When
      temperatures were normalized, both levels were found similar to the control
      group. These results indicate that the increase in serum immunoglobulins levels
      associated with vaccinations, along with, elevations in HSP70 and reduced ghrelin
      levels associated with fever, may be the important parameters in the clinical
      evaluation and follow-up of treatments with vaccines.

PMID- 22477153
TI  - Editorial.

PMID- 22477151
TI  - Combined inhibition of cellular pathways as a future therapeutic option in fatal
      anaplastic thyroid cancer.
AB  - Conventional treatment by surgery, radioiodine, and thyroxin-suppressive therapy
      often fails to cure anaplastic thyroid cancer (ATC). Therefore several attempts
      have been made to evaluate new therapy options by use of "small molecule
      inhibitors". ATC was shown to respond to monotherapeutic proteasome and Aurora
      kinase inhibition in vitro as well as in xenotransplanted tumor cells. Aim of
      this study was to evaluate the effect of combined treatment targeting the
      ubiquitin-proteasome system by bortezomib and Aurora kinases by use of MLN8054.
      Three ATC cell lines (Hth74, C643, and Kat4.1) were used. The antiproliferative
      effect of combined treatment with bortezomib and MLN8054 was assessed by MTT
      assay and cell cycle analysis (FACS). Proapoptotic effects were evaluated by
      measurement of Caspase-3 activity, and effects on VEGF secretion were analyzed by
      ELISA. Compared to mono-application combined treatment with bortezomib and
      MLN8054 resulted in a further decrease of cell density, whereas antagonizing
      effects were found regarding cell cycle progression. Caspase-3 activity was
      increased up to 2.7- and 14-fold by mono-application of MLN8054 and bortezomib,
      respectively. When the two drugs were used in combination, a further enhancement
      of Caspase-3 activity was achieved, depending on the cell line. VEGF secretion
      was decreased following bortezomib treatment and remained unchanged by MLN8054.
      Only in C643 cells, the bortezomib-induced down-regulation was enhanced when
      MLN8054 was applied simultaneously. In conclusion, our data demonstrate that
      targeting the proteasome and Aurora kinases simultaneously results in additional
      antitumoral effects in vitro, especially regarding cell growth and induction of
      apoptosis. The efficacy of this therapeutic approach remains to be revised by in
      vivo and clinical application.

PMID- 22477152
TI  - Recent advances in the genetics of the ALS-FTLD complex.
AB  - There is a clinical and pathological overlap between amyotrophic lateral
      sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). A number of
      autosomal-dominant genes have been described that primarily cause ALS or FTLD
      such as progranulin (GRN), valosin-containing protein (VCP), and TAR DNA-Binding
      Protein (TARDBP), and for each of these conditions there are a small number of
      cases with both ALS and FTLD. Two major genes were described in 2011, which cause
      FTLD and/or ALS within extended kindreds. Ubiquilin2 (UBQLN2) is responsible for
      X-linked FTLD/ALS. A hexanucleotide repeat expansion in C9ORF72 causes chromosome
      9p linked FTLD/ALS and is the most common cause of familial ALS accounting for
      about 40 % of familial cases. Both UBQLN2 and C9ORF72 mutations lead to TDP-43
      positive neuropathology, and C9ORF72-positive cases have p62/ubiquitin-positive
      pathology, which is not stained by TDP-43 antibodies. Ubiquilin2 is one of a
      family of proteins thought to be important in targeting abnormal proteins for
      degradation via lysosomal and proteasomal routes. The pathogenic mechanism of the
      C9ORF72 expansion is unknown but may involve partial haploinsufficiency of
      C9ORF72 and/or the formations of toxic RNA inclusions. The identification of
      mutations in these genes represents an important step forward in our
      understanding of the clinical, pathological, and genetic spectrum of ALS/FTLD
      diseases.

PMID- 22477154
TI  - Effects of grammar instruction and fluency training on the learning of the and a
      by native speakers of japanese.
AB  - In a computer-assisted sentence completion task, the effects of grammar
      instruction and fluency training on learning the use of the definite and
      indefinite articles of English were examined. Forty-eight native Japanese
      speaking students were assigned to four groups: with grammar/accuracy (G/A),
      without grammar/accuracy (N/A), with grammar/fluency (G/F), and without
      grammar/fluency (N/F). In the G/A and N/A groups, training continued until
      performance reached 100% accuracy (accuracy criterion). In the G/F and N/F
      groups, training continued until 100% accuracy was reached and the correct
      responses were made at a high speed (fluency criterion). Grammar instruction was
      given to participants in the G/A and G/F groups but not to those in the N/A and
      N/F groups. Generalization to new sentences was tested immediately after reaching
      the required criterion. High levels of generalization occurred, regardless of the
      type of mastery criterion and whether the grammar instruction was given.
      Retention tests were conducted 4, 6, and 8 weeks after training. Fluency training
      effectively improved retention of the performance attained without the grammar
      instruction. This effect was diminished when grammar instruction was given during
      training. Learning grammatical rules was not necessary for the generalized use of
      appropriate definite and indefinite articles or for the maintenance of the
      performance attained through fluency training.

PMID- 22477155
TI  - The effects of stating contingency-specifying stimuli on compliance in children.
AB  - The present investigation examined whether distinguishing between the
      discriminative and function-altering properties of contingency-specifying stimuli
      (CSS) is of heuristic value in conceptualizing child compliance. Groups of
      "compliant" and "noncompliant" children were instructed to place several blocks
      in a box. During half of the trials the children had an immediate opportunity to
      respond to the instruction (IOR), and during the other trials the children's
      opportunity to respond was delayed by 10 min (DOR). Results showed that 5 of the
      8 children were more likely to comply in the IOR condition, whereas the 3
      remaining children were equally compliant in IOR and DOR conditions. In addition,
      the study investigated the influence of condition presentation sequence on child
      compliance. Thus, half of the children entered the IOR condition first, and the
      other half entered the DOR condition first. Results showed no differences in
      compliance for 3 of 4 children in the IOR-first sequence. However, in the DOR
      first sequence, all children, regardless of classification, were more compliant
      in IOR than in DOR conditions. Presentation order appeared to strongly influence
      compliance and could likely have affected the results of prior investigations.

PMID- 22477156
TI  - Using mand training to establish an echoic repertoire in young children with
      autism.
AB  - This research describes a method that initially establishes a mand repertoire as
      the first component in producing echoic and tact repertoires in young children
      with limited verbal repertoires. The subjects were 3 nonverbal children with
      autism, aged 2.5 to 3.5 years. The results indicated that establishing a mand
      repertoire as the starting point for echoic training produced the acquisition of
      an initial echoic repertoire in all 3 children within the first 10 sessions. Two
      of the children also began tacting during the same period. A mand repertoire was
      acquired by all subjects by the sixth session. Negative vocal behavior was
      rapidly reduced without the use of aversive contingencies by shaping
      inapproapriate vocalizations into acceptable vocal mands. Our discussion analyzes
      those contingencies that contribute to the effectiveness of the manding procedure
      and compares this procedure with the conventional vocal imitation model. We also
      discuss variables that may contribute to the long-term success of language
      training programs and describe strategies for preventing language delay in
      typical infants and children.

PMID- 22477157
TI  - A review of Sundberg and Partington's teaching language to children with autism
      or other developmental disabilities.

PMID- 22477158
TI  - A call for tutorials on alternative approaches to the study of verbal behavior.

PMID- 22477159
TI  - Some additional considerations of protocol analyses.

PMID- 22477160
TI  - Sequential analyses, multiple controlling stimuli, and temporal patterning in
      first-language transmission.
AB  - Although inferences of causality from contingencies are problematic, as Hume
      argued, and are difficult to prove empirically, explanatory accounts of normal
      language acquisition and all remedial interventions rely on presumptions of
      environmental effectiveness. Careful sequential analyses of verbal behaviors can
      strongly corroborate dependencies by means of establishing either (a) contiguous
      contingencies or (b) topographical resemblances between antecedents and delayed
      consequences that could not be explained without assuming such dependencies. The
      promises, as well as the methodological and conceptual challenges, of such
      sequential analyses of verbal training and learning are exemplified on the basis
      of mother-child interactions. Concomitant variation over shorter and longer
      intervals, and immediate as well as lagged contingencies, are interpreted as
      indicators of dependency relationships. By focusing on behavioral evidence,
      extensive similarities or even homologies between first-language training and
      learning and basic behavioral principles established mostly through nonhuman
      research can be demonstrated. Nevertheless, expansions and innovations in the
      behavioral repertoire are suggested as conducive to mutual enrichment of the two
      fields of the experimental analysis of behavior and first-language acquisition.

PMID- 22477161
TI  - Foundations for a natural science of philosophy.
AB  - The functional relations among philosophy, science, technology, and intuition are
      examined. Those domains are each defined as behaviors, and each of them is then
      classified either as verbal, nonverbal, or both. Finally, those classes of
      behavior are organized into one integral behavioral system. The concept of a
      science of philosophy is introduced. A science and technology of philosophy are
      not only possible but necessary. Such an approach to the discipline of philosophy
      could lead to a new disciplinary structure for philosophy. Philosophy could be
      taught in academic departments as a verbal behavioral science. The discipline of
      behaviorology provides the foundations necessary to capacitate the traditional
      discipline of philosophy as a science and technology of verbal behavior
      commensurate with its potential cultural mission.

PMID- 22477162
TI  - Distribution characteristics of organochlorine pesticides in surface and vertical
      sediments from the Zha Long Wetland, China.
AB  - INTRODUCTION: The Zha Long Wetland, the first water bird conservation area in
      China, lies on the northern bank of the Song Nen Plain with an area of 2,100
      km(2). In many areas of the Zha Long Wetland, water pollution has led to a
      decrease in the wetland's ecological function, vegetation degradation, a decrease
      in the number of bird species, and the depletion of fish resources. MATERIALS AND
      METHODS: The sediments used in this study were collected from the surface
      sediment of seven sites and from different depths in three types of marshes in
      the Zha Long Wetland in northeast China in late October 2006. The levels and
      distribution patterns of 17 organochlorine pesticides (OCPs; alpha-HCH, beta-HCH,
      gamma-HCH, delta-HCH, p,p'-DDE, p,p'-DDD, p,p'-DDT, endosulfan I, endosulfan II,
      endosulfan sulfate, heptachlor, heptachlor epoxide, aldrin, dieldrin, endrin,
      endrin aldehyde, and methoxychlor) in surface sediments as well as
      hexachlorocyclohexane (HCH) and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane
      (DDT) in vertical sediments were investigated. RESULTS AND DISCUSSION: The
      concentrations of HCHs, DDTs, endosulfans, heptachlors, aldrin, and methoxychlor
      in surface sediments ranged from 10.44 to 41.97 ng/g, nd (undetectable levels) to
      211.88 ng/g, nd to 69.89 ng/g, nd to 28.10 ng/g, 9.81 to 623.83 ng/g, and from nd
      to 3.99 ng/g, respectively. The highest levels of OCPs were detected in
      Tangtugangzi at a total concentration of 727.72 ng/g, where the dominant compound
      was endrin at a concentration of 483.04 ng/g. In the vertical sediments, the HCHs
      and DDTs were in the ranges of nd-136.00 and nd-214.06 ng/g, respectively.
      CONCLUSIONS: Different distributions of HCHs, DDTs, and other OCPs indicated that
      they originated from different contamination sources. Composition analyses in
      surface sediments indicated recent OCP usage or discharge at some sample sites in
      the Zha Long Wetland.

PMID- 22477163
TI  - Removal of Cu, Zn, and Cd from aqueous solutions by the dairy manure-derived
      biochar.
AB  - PURPOSE: Biochar derived from waste biomass is now gaining much attention for its
      function as a biosorbent for environmental remediation. The objective of this
      study was to determine the effectiveness of biochar as a sorbent in removing Cd,
      Cu, and Zn from aqueous solutions. METHODS: Biochar was produced from dairy
      manure (DM) at two temperatures: 200  degrees C and 350  degrees C, referred to
      as DM200 and DM350, respectively. The obtained biochars were then equilibrated
      with 0-5 mM Cu, Zn or Cd in 0.01 M NaNO(3) solution for 10 h. The changes in
      solution metal concentrations after sorption were evaluated for sorption capacity
      using isotherm modeling and chemical speciation Visual MINTEQ modeling, while the
      solid was collected for species characterization using infrared spectroscopy and
      X-ray elemental dot mapping techniques. RESULTS: The isotherms of Cu, Zn, and Cd
      sorption by DM200 were better fitted to Langmuir model, whereas Freundlich model
      well described the sorption of the three metals by DM350. The DM350 were more
      effective in sorbing all three metals than DM200 with both biochars had the
      highest affinity for Cu, followed by Zn and Cd. The maximum sorption capacities
      of Cu, Zn, and Cd by DM200 were 48.4, 31.6, and 31.9 mg g(-1), respectively, and
      those of Cu, Zn, and Cd by DM350 were 54.4, 32.8, and 51.4 mg g(-1),
      respectively. Sorption of the metals by the biochar was mainly attributed to
      their precipitation with PO(4)(3-) or CO(3)(2-) originating in biochar, with less
      to the surface complexation through -OH groups or delocalized pi electrons. At
      the initial metal concentration of 5 mM, 80-100 % of Cu, Zn, and Cd retention by
      DM200 resulted from the precipitation, with less than 20 % from surface
      adsorption through phenonic -OH complexation. Among the precipitation, 20-30 % of
      the precipitation occurred as metal phosphate and 70-80 % as metal carbonate. For
      DM350, 75-100 % of Cu, Zn, and Cd retention were due to the precipitation, with
      less than 25 % to surface adsorption through complexation of heavy metal by
      phenonic -OH site or delocalized pi electrons. Among the precipitation, only less
      than 10 % of the precipitation was present as metal phosphate and more than 90 %
      as metal carbonate. CONCLUSIONS: Results indicated that dairy manure waste can be
      converted into value-added biochar as a sorbent for sorption of heavy metals, and
      the mineral components originated in the biochar play an important role in the
      biochar's high sorption capacity.

PMID- 22477164
TI  - Daily, seasonal and monthly variations in ozone levels recorded at the Turia
      river basin in Valencia (Eastern Spain).
AB  - INTRODUCTION: The Turia river basin, located in the east of the Iberian
      Peninsula, drains into the Mediterranean Sea near the city of Valencia
      (population, 814,208). The predominance of sea-breeze fluxes favours the inland
      transport of pollutants from the city up the basin where ozone concentrations
      exceeding the threshold for protection of human health are systematically
      recorded during the summer months. METHODS: This work analyses the variability in
      ozone levels by examining their spatial and temporal distribution in a
      Mediterranean river basin downwind from a city within the period 2005-2008.
      Orographic determinants and atmospheric fluxes induce strong variations in ozone
      measurements, even on relatively close locations. CONCLUSIONS: Results show a
      different behaviour of the monthly means and the daily cycles depending on the
      season of the year and the measuring environment, with summer/winter ratios
      ranging from 2.4 in cities to 1.6 inland, and mean values always higher in the
      interior of the basin. Daily cycles show significant summer/winter differences
      related to the predominant situations of anticyclonic stability in winter, which
      limit ventilation, and the predominant breeze circulations in summer. Results
      also show a "weekend effect" at urban and medium-distance stations. At the most
      inland station, the weekend/weekday behaviour differs according to the season of
      the year; weekend ozone levels are higher in spring, autumn and winter, and lower
      in summer, coinciding with the predominance of local wind cycles that favour air
      mass penetration inland from the coast.

PMID- 22477165
TI  - Diphenyl diselenide attenuates hepatic and hematologic toxicity induced by
      chlorpyrifos acute exposure in rats.
AB  - PURPOSE: In this study, we investigated the effect of diphenyl diselenide
      [(PhSe)(2)] on chlorpyrifos (CPF)-induced hepatic and hematologic toxicity in
      rats. METHODS: Rats were pre-treated with (PhSe)(2) (5 mg/kg) via the oral route
      (oral gavage) once a day for 7 days. On the eighth and ninth days, rats were
      treated with (PhSe)(2) (5 mg/kg) 30 min prior to CPF (50 mg/kg, by subcutaneous
      route). The aspartate aminotransferase, alanine aminotransferase, and lactate
      dehydrogenase activities were determined in plasma of rats. Lipid peroxidation,
      protein carbonyl, and non-protein thiol levels as well as catalase, superoxide
      dismutase, glutathione peroxidase, glutathione reductase, and gluthatione S
      transferase activities were determined in livers of rats. Hematological
      parameters were also determined. RESULTS: The results showed that CPF caused
      hepatic oxidative damage, as demonstrated by an increase in lipid peroxidation
      and protein carbonyl levels which was associated with a decrease in antioxidant
      defenses. CPF exposure caused a reduction in the leukocyte, indicating
      hematologic toxicity. (PhSe)(2) was effective in attenuating these toxic effects
      caused by CPF exposure in rats. CONCLUSIONS: The results indicated that (PhSe)(2)
      was effective in protecting the hepatic and hematologic toxicity induced by acute
      CPF exposure in rats.

PMID- 22477166
TI  - The importance of physical strength to human males.
AB  - Fighting ability, although recognized as fundamental to intrasexual competition
      in many nonhuman species, has received little attention as an explanatory
      variable in the social sciences. Multiple lines of evidence from archaeology,
      criminology, anthropology, physiology, and psychology suggest that fighting
      ability was a crucial aspect of intrasexual competition for ancestral human
      males, and this has contributed to the evolution of numerous physical and
      psychological sex differences. Because fighting ability was relevant to many
      domains of interaction, male psychology should have evolved such that a man's
      attitudes and behavioral responses are calibrated according to his formidability.
      Data are reviewed showing that better fighters feel entitled to better outcomes,
      set lower thresholds for anger/aggression, have self-favoring political
      attitudes, and believe more in the utility of warfare. New data are presented
      showing that among Hollywood actors, those selected for their physical strength
      (i.e., action stars) are more likely to believe in the utility of warfare.

PMID- 22477167
TI  - Iatrogenic infection of a colonic cystic lymphangioma following cold-forceps
      biopsy.

PMID- 22477168
TI  - Endoscopic removal of an impacted acupuncture needle in the duodenum.

PMID- 22477169
TI  - Subcapsular hepatic hematoma post ERCP: a rare or an underdiagnosed complication?

PMID- 22477170
TI  - Esophageal papillomatosis complicated by squamous cell carcinoma.

PMID- 22477171
TI  - Isolated Kaposi sarcoma of the stomach.

PMID- 22477172
TI  - Multiple esophagopleural and esophagobronchial fistulas in a patient with Crohn's
      disease.

PMID- 22477173
TI  - The "U-wire" technique during ERCP for easy guide wire passage through occluded
      uncovered metal stents.

PMID- 22477174
TI  - Duodenal duplication cyst causing acute recurrent pancreatitis, managed
      curatively by endoscopic marsupialization.

PMID- 22477175
TI  - Resolution of a refractory severe biliary stricture using a diathermic sheath.

PMID- 22477176
TI  - Esophageal stricture following successful resolution of a mediastinal pseudocyst
      by endoscopic transpapillary drainage.

PMID- 22477177
TI  - A rare case of double primary cancer of the colon with parotid gland metastasis.

PMID- 22477178
TI  - Risk of biodegradable stent-induced hypergranulation causing re-stenosis of a
      gastric conduit after esophageal resection.

PMID- 22477179
TI  - Autoamputation of a large pedunculated colon polyp.

PMID- 22477180
TI  - Severe case of intestinal vasculitis: knife's edge diagnosis and treatment.

PMID- 22477181
TI  - Long-term dysphagia due to bronchogenic cyst of the esophagus.

PMID- 22477182
TI  - An improved method for nasojejunal feeding tube placement in     patients
      requiring endoscopic nasobiliary drainage.

PMID- 22477183
TI  - Natural products as potential anticonvulsants: caffeoylquinic acids.
AB  - Current anticonvulsant therapies are generally directed at symptomatic treatment
      by suppressing excitability within the brain. Consequently, they have adverse
      effects such as cognitive impairment, dependence, and abuse. The need for more
      effective and less toxic anticonvulsants has generated renewed interest in
      natural products for the treatment of convulsions. Caffeoylquinic acids (CQs) are
      naturally occurring phenolic acids that are distributed widely in plants. There
      has been increasing interest in the biological activities of CQs in diseases of
      the central nervous system. In this issue, Nugroho et al. give evidence for the
      anticonvulsive effect of a CQ-rich extract from Aster glehni Franchet et Sckmidt.
      They optimized the extract solvent conditions, resulting in high levels of CQs
      and peroxynitrite-scavenging activity. Then, they investigated the sedative and
      anticonvulsive effects in pentobarbital- and pentylenetetrazole-induced models in
      mice. The CQ-rich extract significantly inhibited tonic convulsions as assessed
      by onset time, tonic extent, and mortality. They suggested that the CQ-rich
      extract from A. glehni has potential for treating convulsions. This report
      provides preclinical data which may be used for the development of
      anticonvulsants from natural products.

PMID- 22477184
TI  - Development of PAC-14028, a novel transient receptor potential vanilloid type 1
      (TRPV1) channel antagonist as a new drug for refractory skin diseases.
AB  - The transient receptor potential vanilloid 1 (TRPV1) is a member of nonselective
      cation channels and has been implicated in the progression of neurogenic
      inflammation and nociception. Through the synthesis of over 2,000 new compounds,
      a novel non-vanilloid TRPV1 antagonist PAC-14028 was discovered. As well as ideal
      physicochemical and pharmacokinetic properties, PAC-14028 showed meaningful
      efficacies against diverse disease models that include visceral pain,
      inflammatory bowel disease, and inflammatory pain. Of note, PAC-14028 effectively
      attenuates atopic dermatitis and pruritus without significant adverse effects,
      which is a substantial benefit over conventional pharmacotherapy. This report
      introduces the potential of a novel TRPV1 antagonist PAC-14028 as a new drug for
      atopic dermatitis and pruritus.

PMID- 22477185
TI  - Emerging roles of the ubiquitin-proteasome system in the steroid receptor
      signaling.
AB  - The ubiquitin-proteasome system (UPS) harbors elaborated protein quality control
      systems in eukaryotic cells. Recently, the UPS is emerging as an important
      regulator in controlling the magnitude and the duration of the steroid hormone
      responses. Upon steroid hormone stimuli, their cognate steroid receptors,
      including androgen receptor (AR) and estrogen receptor (ER), not only mediate
      transcriptional activation, but also undergo ubiquitination and consequent
      proteasomal degradation. Many reports have strongly suggested that UPS machinery,
      particularly the E3 ubiquitin ligases, are closely involved in the receptor
      mediated gene expression regulation. Both ligand-dependent and -independent
      recruitment of E3 ubiquitin ligases often prompt the degradation of target
      steroid receptors and correct transcription activation. Here, we review that the
      deep mechanistic connections between AR and ER-dependent transcription and the
      UPS for the correct expression of target genes. We also emphasize that this
      regulatory system has a significant potential for future clinical application,
      including the treatment of breast and prostate cancers by facilitating the
      degradation of related hormone receptors.

PMID- 22477186
TI  - Antimicrobial peptides: their physicochemical properties and therapeutic
      application.
AB  - Antibiotic resistance has become a global public health problem, thus there is a
      need to develop a new class of antibiotics. Natural antimicrobial peptides have
      got an increasing attention as potential therapeutic agents. Antimicrobial
      peptides are small cationic peptides with broad antimicrobial activity. They can
      serve as critical defense molecules protecting the host from the invasion of
      bacteria. Even though they possess a different mode of action compared to
      traditional antibiotics, antimicrobial peptides couldn't go into the drug markets
      because of problems in application such as toxicity, susceptibility to
      proteolysis, manufacturing cost, size, and molecular size. Nevertheless,
      antimicrobial peptides can be new hope in developing novel, effective and safe
      therapeutics without antibiotic resistance. Thus, it is necessary to discover new
      antimicrobial sources in nature and study their structures and physicochemical
      properties more in depth.

PMID- 22477187
TI  - A new flavonol glycoside from Hylomecon vernalis.
AB  - Purification of a MeOH extract from the aerial parts of Hylomecon vernalis Maxim.
      (Papaveraceae) using column chromatography furnished a new acetylated flavonol
      glycoside (1), together with twenty known phenolic compounds (2-21). Structural
      elucidation of 1 was based on 1D- and 2D-NMR spectroscopy data analysis to be
      quercetin 3-O-[4'''-O-acetyl-alpha-L-arabinopyranosyl]-(1'''->6")-beta-D
      galactopyranoside (1). The structures of compounds 2-21 were elucidated by
      spectroscopy and confirmed by comparison with reported data; quercetin 3-O-[2'''
      O-acetyl-alpha-L-arabinopyranosyl]-(1'''->6")-beta -D-galactopyranoside (2),
      quercetin 3-O-alpha-L-arabinopyranosyl-(1'''->6")-beta-D-galactopyranoside (3),
      quercetin 3-O-beta -D-galactopyranoside (4), kaempferol 3,7-O-alpha-L
      dirhamnopyranoside (5), diosmetin 7-O-beta -D-glucopyranoside (6), diosmetin 7-O
      beta -D-xylopyranosyl-(1'''->6")-beta-D-glucopyranoside (7), p-hydroxybenzoic
      acid (8), protocatechuic acid (9), caffeic acid (10), 6-hydroxy-3,4-dihydro-1-oxo
      beta -carboline (11), (Z)-3-hexenyl-beta -D-glucopyranoside (12), (E)-2-hexenyl
      beta -D-glucopyranoside (13), (Z)-3-hexenyl-alpha-Larabinopyranosyl-(1"->6')-beta
      D-glucopyranoside (14), oct-1-en-3-yl-alpha-L-arabinopyranosyl-(1"->6')-beta-D
      glucopyranoside (15), benzyl-beta-D-apiofuranosyl-(1"->6')-beta-D-glucopyranoside
      (16), benzyl-alpha-L-arabinopyranosyl-(1"->6')-beta-D-glucopyranoside (17),
      benzyl-beta-D-xylopyranosyl-(1"->6')-beta-Dglucopyranoside (18), 2-phenylethyl
      alpha-L-arabinopyranosyl-(1"->6')-beta-D-glucopyranoside (19), 2-phenylethyl-beta
      D-apiofuranosyl-(1"->6')-beta-D-glucopyranoside (20), and aryl-beta-D
      glucopyranoside (21). Compounds 2-21 were isolated for the first time from this
      plant. The isolated compounds were tested for cytotoxicity against four human
      tumor cell lines in vitro using a Sulforhodamin B bioassay.

PMID- 22477188
TI  - Phytochemical studies of the phenolic substances in Aster glehni extract and its
      sedative and anticonvulsant activity.
AB  - On high performance liquid chromatography, the caffeoylquinic acid (CQ) occupying
      the highest proportion of the water-ethanol (7:3) extract of Aster glehni
      (Compositae) leaves was 3-Op-coumaroylquinic acid (46.10 +/- 4.22 mg/g of dried
      weight) among CQs tested. The IC50 of the water-ethanol (7:3) extract was 4.23 +/
      0.24 MUg/mL in the peroxynitrite (ONOO(-))-scavenging assay. Phytochemical
      isolation from A. glehni extract yielded three kaempferol glycosides. The water
      ethanol (7:3) extract and both p-coumaric acid and caffeic acid, phenylpropanoid
      moieties of CQs, had sedative effects in pentobarbital-induced sleeping time in
      mice and anticonvulsant effects in pentylenetetrazole-induced mice. Furthermore,
      the phenolic substance-rich W-E (7:3) extract of A. glehni could be used to treat
      anxiety or convulsion partly due to its peroxynitrite-scavenging mechanism.

PMID- 22477189
TI  - Biologically active C-alkylated flavonoids from Dodonaea viscosa.
AB  - A new C-alkylated flavonoid (5,7-dihydroxy-3'-(4"-acetoxy-3"-methylbutyl)-3,6,4'
      trimethoxyflavone (1), along with two known C-alkylated flavonoids (5,7-dihydroxy
      3'-(3-hydroxymethylbutyl)-3,6,4'-trimethoxyflavone (2), 5,7,4'-trihydroxy-3'-(3
      hyroxymethylbutyl)-3,6-dimethoxyflavone (3) and two new source C-alkylated
      flavonoids (5,7-dihydroxy-3'-(2-hydroxy-3-methyl-3-butenyl)-3,6,4'
      trimethoxyflavone (4), 5,7,4'-trihydroxy-3,6-dimethoxy-3'-isoprenyl-flavone (5)
      were isolated from the aerial parts of Dodonaea viscosa. The structures of all
      compounds were established on the basis of 1D and 2D NMR spectroscopy and mass
      spectrometry. The isolated compounds were evaluated for their inhibitory effect
      on urease and alpha-chymotrypsin enzyme. All the compounds (1-5) exhibited mild
      inhibition against urease but remained recessive in case of alpha-chymotrypsin.

PMID- 22477190
TI  - Synthesis of new pyrazole, triazole, and thiazolidine-pyrimido [4, 5-b] quinoline
      derivatives with potential antitumor activity.
AB  - 2-Hydrazinyltetrahydropyrimido [4, 5-b] quinolin-4(3H)-one (3) was prepared by
      desulfurization reaction of S- and N-dimethyl derivatives 2 with hydrazine
      hydrate. Reactions of (3) with malonitrile, carbondisulfide, potassium
      thiocyanate, phthalic anhydride and aromatic aldehydes afforded 3, 5-di
      aminopyrazolopyrimido [4, 5-b] quinoline (4), triazolotetrahydropyrimido [4, 5-b]
      quinoline (5), aminotriazolopyrimido [4, 5-b] quinoline (6),
      aminophthalimidopyrimido [4, 5-b] quinoline (7) and N-arylidene hydrazinepyrimido
      [4, 5-b] quinoline 8a-d, respectively. Furthermore, 8a-d reacted with
      mercaptoacetic acid gave the thiazolidinonepyrimido [4, 5-b] quinoline 9a-d,
      which afforded the thiazolotriazolopyrimido [4, 5-b] quinolinone 10a-d upon
      treatment with ethanolic potassium hydroxide. The newly synthesized compounds
      were characterized by elemental analyses, IR, 1H-NMR, 13C-NMR and mass
      spectrometer. The investigated compounds were screened for their cytotoxicity.
      Compounds 4, 6 and 5 exhibited potent antitumor activity.

PMID- 22477191
TI  - A facile synthesis of emodin derivatives, emodin carbaldehyde, citreorosein, and
      their 10-deoxygenated derivatives and their inhibitory activities on MU-calpain.
AB  - A new procedure for the preparation of emodin carbaldehyde and citreorosein was
      described, in which, omega,omega'-dibromomethylemodin triacetate was prepared as
      a key intermediate by NBSmediated bromination of 1,3,8-triacetylemodin. Reduction
      of emodin and citreorosein with SnCl(2) in a 1:1 mixture of HOAc and HCl afforded
      the corresponding anthrones in 90% and 92% yield, respectively, while the
      corresponding 10-desoxyemodin carbaldehyde was prepared by MnO(2) oxidation of 10
      desoxycitreorosein. 10-Desoxycitreorosein and emodin carbaldehyde showed feasible
      MU-calpain inhibitory activities with IC(50) values of 20.15 and 25.77 M,
      respectively.

PMID- 22477192
TI  - Novel human umbilical vein endothelial cells (HUVEC)-apoptosis inhibitory
      phytosterol analogues: insight into their structure-activity relationships.
AB  - Design, synthesis and insight into the structure-activity relationships (SAR) of
      phytosterol analogues as novel antiapoptotic agents are described. In particular,
      the non-branched alkyl chain at C24 and the pseudosugar moiety at C3 hydroxyl
      group turned out crucial for the inhibition of human umbilical vein endothelial
      cells (HUVEC) apoptosis.

PMID- 22477193
TI  - Tetrahydroanthraquinone and xanthone derivatives from the marine-derived fungus
      Trichoderma aureoviride PSU-F95.
AB  - Trichodermaquinone (1) and trichodermaxanthone (2) were isolated from the marine
      derived fungus Trichoderma aureoviride PSU-F95 together with eleven known
      compounds. The structures were interpreted by spectroscopic methods. Known
      coniothranthraquinone 1 and emodin displayed strong antibacterial activity
      against methicillin-resistant Staphylococcus aureus with the MIC values of 8 and
      4 MUg/mL, respectively.

PMID- 22477194
TI  - Synthesis and evaluation of peptidyl alpha,beta-unsaturated carbonyl derivatives
      as anti-malarial calpain inhibitors.
AB  - Malarial calpain is a cysteine protease believed to be a central mediator
      essential for parasitic activities. N-Acetyl-L-leucyl-L-leucyl-L-norleucinal
      (ALLN), a calpain inhibitor, showed an excellent inhibitory effect on the
      erythrocytic stages of Plasmodium falciparum. However the aldehyde group of ALLN
      makes it susceptible to metabolism. Therefore, we designed alpha,beta-unsaturated
      carbonyl peptides that could serve as electrophiles for cysteine residues in
      calpain. Among the synthetic analogs based on the structure of ALLN, peptidyl
      esters 7, 8 and 9 showed the most potent anti-malarial effects, with the same
      IC50 values of 5.0 MUM. Also they showed the high selective toxicity for the
      malaria versus Hela cell with 40.6, 69.2 and 24.3 fold for 7, 8 and 9,
      respectively. Dipeptidyl alpha,beta-unsaturated carbonyl derivatives consisting
      of two amino acids gave better anti-malarial effects than those consisting with
      one amino acid. The fluctuation in anti-malarial activity with small changes in
      chemical structure indicates the possibilities of improving synthetic analogs.

PMID- 22477195
TI  - Bioassay-guided isolation of fatty acid synthase inhibitory diterpenoids from the
      roots of Salvia miltiorrhiza Bunge.
AB  - Fatty acid synthase (FAS) is considered as a novel drug target for the
      development of anticancer and anti-obesity agents. Bioassay-guided fractionation
      of a n-hexane-soluble extract prepared from the roots of Salvia miltiorrhiza
      Bunge (Labiatae), using an in vitro enzyme assay, led to the isolation of five
      abietane diterpenoids: 15,16-dihydrotanshinone I (1), cryptotanshinone (2),
      tanshinone I (3), tanshinone IIA (4), and dansenspiroketallactone (5). Compounds
      1-5 were tested for their in vitro FAS inhibitory activity and, except for
      compound 5 (IC(50) > 100 MUM), compounds 1-4 inhibited the enzyme activity with
      IC(50) values ranging from 12.0 to 30.3 MUM. Our findings may be partially
      related to the anticancer activity of abietane diterpenoids from the plant,
      suggesting a further study on the anticancer potential of tanshinone derivatives.

PMID- 22477196
TI  - Design and in vitro and in vivo characterization of mucoadhesive matrix pellets
      of metformin hydrochloride for oral controlled release: a technical note.
AB  - The aim of the current work was to design and develop matrix pellets of hydroxy
      propyl methyl cellulose K200M and microcrystalline cellulose in an admixture for
      a mucoadhesive gastroretentive drug delivery system. Pellets containing metformin
      hydrochloride (500 mg) were prepared by the pelletization technique using an
      extruder-spheronizer. Pellets were characterized by differential scanning
      calorimetry (DSC), x-ray diffraction (XRD), scanning electron microscopy (SEM),
      circularity, roundness, percent drug content, percent production yield, in vitro
      swelling, ex vivo mucoadhesion, in vitro drug release and in vivo x-ray imaging
      studies. Optimized pellets were sufficiently porous spheroids, free flowing, had
      smooth surfaces, had yields up to 75.45 +/- 0.52% and had drug content up to
      96.45 +/- 0.19%. The average particle size of formulations MF2 and MF6 were 1.13
      +/- 0.41 mm and 1.22 +/- 0.18 mm, respectively. Formulation MF6 exhibited strong
      adhesion, about 94.67%, to goat mucosal tissue, and the desired in vitro
      swelling, with a sustained drug release profile for 12 h and with retention in
      the upper small intestine of rabbits for 10 h. We conclude that hydroxy propyl
      methyl cellulose K200M and microcrystalline cellulose at a 2.80:1.00 w/w ratio
      could be an effective carrier for multiple unit controlled delivery of metformin
      hydrochloride.

PMID- 22477197
TI  - Role of a novel pyridostigmine bromide-phospholipid nanocomplex in improving oral
      bioavailability.
AB  - A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared
      to increase the bioavailability of PB. A central composite design approach was
      employed for process optimization. The physicochemical properties of PBPLC were
      investigated by means of differential scanning calorimetry, ultraviolet
      spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water
      partition coefficient. The intestinal permeability of PBPLC was observed via a
      single pass intestinal perfusion in rats. After oral administration of PBPLC, the
      concentrations of PB at predetermined time points were determined by HPLC, and
      the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple
      linear regression analysis for process optimization revealed that the optimal
      PBPLC was obtained when the values of X(1), X(2), and X(3) were 8, 40 degrees C,
      and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC
      with the optimized formulation were 204.60 nm and -25.12 mV, respectively. Non
      covalent interactions between PB and phospholipids were found in the PBPLC. The n
      octanol/water partition coefficient of PBPLC was substantially increased. PBPLC
      had better intestinal permeability in comparison with free PB. Mean plasma drug
      concentration-time curves of PBPLC and free PB after oral administration were
      both in accordance with the two-compartment open model. The values of
      pharmacokinetic parameters of PBPLC and free PB were the peak time (T(max)) 2 h
      vs 2 h, the maximum concentration (C(max)) 22.79 MUg/mL vs 6.00 MUg/mL, and the
      value of the area under the concentration vs time curve (AUC(0-infinity)) 7128.21
      MUg.min/mL vs 1772.36 MUg.min/mL, respectively. In conclusion, compared with free
      PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due
      to its higher lipophilicity and permeability.

PMID- 22477198
TI  - Effects of cysteine on the pharmacokinetics of paclitaxel in rats.
AB  - Paclitaxel is a P-gp substrate and metabolized via CYP2C and 3A subfamily in
      rats. It has been reported that cysteine causes the changes in expression of CYP
      isozymes and intestinal P-gp mediated efflux activity in rats. Thus, the effects
      of cysteine on the pharmacokinetics of intravenous and oral paclitaxel were
      investigated in rats. After intravenous administration of paclitaxel (30 mg/kg)
      to control (CON), single cysteine treatment (ST) and cysteine treatment for a
      week (CT) rats, the pharmacokinetic parameters were comparable among three groups
      of rats. Also the pharmacokinetic parameters between CON and ST rats were
      comparable after oral administration of paclitaxel (30 mg/kg) to rats. These
      results are consistent with that oral cysteine supplement on a single day did not
      considerably inhibit the metabolism of paclitaxel via hepatic and/or intestinal
      CYP3A subfamily and P-gp mediated efflux of paclitaxel in the liver and/or
      intestine both after intravenous and oral administration to rats. After oral
      administration of paclitaxel (30 mg/kg) to rats, the greater AUC(06 h) in CT rats
      was mainly due to that oral cysteine supplement for seven consecutive days
      enhanced the gastrointestinal absorption of paclitaxel compared with those in CON
      and ST rats.

PMID- 22477199
TI  - Preparation and determination of optical purity of gamma-lysine modified peptide
      nucleic acid analogues.
AB  - Peptide nucleic acids (PNAs) are DNA analogues in which the nucleic acid backbone
      is replaced by a pseudopeptide backbone and nucleobases are attached to the
      backbone by methylene carbonyl linkers. gamma-Carbon modification of the PNA
      structure allows monomers, and subsequently oligomers, with improved properties
      to be obtained. In this study, we report the convenient synthesis of gamma-lysine
      modified PNA monomers for pyrimidine bases (thymine and cytosine) with high
      optical purity (> 99.5%) and direct enantiomer separation of gamma-lysine
      modified PNA analogs, using chiral HPLC to determine the optical purity.

PMID- 22477200
TI  - Pharmacokinetic and ulcerogenic studies of naproxen prodrugs designed for
      specific brain delivery.
AB  - Naproxen (Nap) is an NSAID used as a neuroprotective agent to treat several
      neurodegenerative diseases. The observed limited brain bioavailability of the
      drug prompted the design of several chemical delivery systems. We report the
      synthesis and preliminary in vitro and in vivo investigations of Nap prodrugs
      with dihydropyridine (I) and ascorbic acid (II) through an ester spacer to target
      specific brain delivery of Nap. The purpose of this study was to determine the
      brain bioavailability of Nap after oral administration of the prodrugs in rats.
      The results showed moderate oral bioavailability of prodrugs (AUC = 53-94 h .
      MUg/mL) in rats compared with parent Nap (AUC = 155 h . MUg/mL) at equimolar
      doses. Contrarily, there was a twofold increase in Nap levels in the brain with
      the prodrugs compared to parent Nap. The enhanced brain bioavailability may be
      attributed to the specific carrier system in addition to the reduced percentage
      of plasma protein binding of Nap. Plasma protein binding of the tested prodrugs
      was investigated in vitro using equilibrium dialysis. The percentage of plasma
      free fraction of prodrugs (9-15%) was significantly greater than that of Nap
      (about 5%) when tested at 20 MUM, illustrating more available prodrug to cross
      the blood brain barrier. A significant decrease in gastric ulcerogenicity of the
      prodrugs compared with parent Nap was also noted. In conclusion, oral
      dihydropyridine and ascorbate prodrugs for brain site-specific delivery of Nap
      may be promising candidates for safe, chronic use of NSAIDs for the treatment of
      neurodegenerative diseases.

PMID- 22477201
TI  - Evaluation of interstitial protein delivery in multicellular layers model.
AB  - The limited efficacy of anticancer protein drugs is related to their poor
      distribution in tumor tissue. We examined interstitial delivery of four model
      proteins of different molecular size and bioaffinity in multicellular layers
      (MCL) of human cancer cells. Model proteins were tumor necrosis factor-related
      apoptosis-including ligand (TRAIL), cetuximab, RNase A, and IgG. MCLs were
      cultured in Transwell inserts, exposed to drugs, then cryo-sectioned for image
      acquisition using fluorescence microscopy (fluorescent dye-labeled TRAIL, RNase
      A, IgG) or immunohistochemistry (cetuximab). TRAIL and cetuximab showed partial
      penetration into MCLs, whereas RNase A and IgG showed insignificant penetration.
      At 10-fold higher dose, a significant increase in penetration was observed for
      IgG only, while cetuximab showed an intense accumulation limited to the front
      layers. PEGylated TRAIL and RNase A formulated in a heparin-Pluronic (HP) nanogel
      showed significantly improved penetration attributable to increased stability and
      extracellular matrix binding, respectively. IgG penetration was significantly
      enhanced with paclitaxel pretreatment as a penetration enhancer. The present
      study suggests that MCL culture may be useful in evaluation of protein delivery
      in the tumor interstitium. Four model proteins showed limited interstitial
      penetration in MCL cultures. Bioaffinity, rather than molecular size, seems to
      have a positive effect on tissue penetration, although high binding affinity may
      lead to sequestration in the front cell layers. Polymer conjugation and
      nanoformulation, such as PEGylation and HP nanogel, or use of penetration
      enhancers are potential strategies to increase interstitial delivery of
      anticancer protein drugs.

PMID- 22477202
TI  - Ursolic acid-induced apoptosis in K562 cells involving upregulation of PTEN gene
      expression and inactivation of the PI3K/Akt pathway.
AB  - Ursolic acid (UA), a pentacyclic triterpenoid derived from a variety of medicinal
      plants, exhibits potent anticancer activity against many types of cancer cells.
      However, the anticancer mechanism of UA is not clearly understood. Suppression of
      phosphatase and a tensin homolog deleted on chromosome 10 (PTEN) gene expression
      leading to activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway
      has been observed in many cancers including leukemia, making the PTEN gene and
      PI3K/Akt pathway a central target for cancer therapy. Here, we demonstrated that
      UA was able to inhibit growth, induce apoptosis in a human chronic myelogenous
      leukemia cell line (K562 cells) via upregulation of PTEN gene expression, inhibit
      Akt kinase activity, change mitochondrial transmembrane potential and reduce the
      release of cytochrome c and the activity of caspases. These results suggest that
      UA may elicit its strong antitumor effects via upregulation of the PTEN gene and
      inhibition of the PI3K/Akt pathway.

PMID- 22477203
TI  - Anti-inflammatory changes of gene expression by Artemisia iwayomogi in the LPS
      stimulated human gingival fibroblast: microarray analysis.
AB  - The leaves and stems of Asteraceae Artemisia iwayomogi (Ai) for a long time have
      been known to inhibit inflammatory cytokine production and allergic reactions,
      and have been used to treat liver diseases. It needs to be elucidated in terms of
      global gene expression whether Ai has an influence as an anti-inflammatory agent
      on the cultured human gingival fibroblast stimulated with lipopolysaccharide
      (LPS). This study investigated the anti-inflammatory changes of the genes by Ai
      using the Affymetrix genechip human gene 1.0 ST array when the cultured human
      gingival fibroblast was treated with LPS. It was observed that the inflammation-
      and immune response-related genes were activated by LPS challenge in the cultured
      human gingival fibroblast. The array analysis showed that 65 of the 344 genes up
      regulated by LPS stimulation, when compared to the control, were down-regulated
      by the Ai treatment. A number of inflammation- and immune response-related genes
      of the 65 genes were found. In addition, 78 of the 164 genes down-regulated by
      the LPS, when compared to the control, were up-regulated by the Ai treatment. The
      regulatory patterns of the representative genes were correlated with the real
      time RT-PCR analysis. The Ai extract and its specific components, scopolin and
      scopoletin, significantly hindered the production of inflammatory mediators such
      as IL-6, TNF-alpha and nitrite in the LPS-challenged fibroblast. This study
      suggests that Ai can comprehensively inhibit the activation of the inflammation-
      and immune response-related genes and the inflammatory mediators in the human
      gingival fibroblast.

PMID- 22477204
TI  - In vitro antiproliferative effects of the indole alkaloid vallesiachotamine on
      human melanoma cells.
AB  - In course of a screening for small molecules presenting potential anticancer
      properties, a known monoterpene indole alkaloid named vallesiachotamine was
      isolated from the leaves of Palicourea rigida (Rubiaceae) collected in the
      Brazilian Cerrado. The structure was determined by spectroscopic methods, mainly
      1D- and 2D-NMR and its biological activities were investigated on cultured human
      (SK-MEL-37) melanoma cells. In vitro cytotoxicity was evaluated by the 3-(4, 5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory
      concentration (IC(50)) was 14.7 +/- 1.2 MUM for 24 h of drug exposure. Flow
      cytometry analysis revealed that vallesiachotamine induced G0/G1 arrest and
      increased the proportion of sub-G1 hypodiploid cells (at 11 MUM and 22 MUM) and
      this effect was not dependent on time of incubation. At these concentrations, a
      typical ladder was observed by agarose gel electrophoresis of the extracted DNA.
      Treatment of cells with 50 MUM vallesiachotamine for 24 h caused extensive
      cytotoxicity and necrosis. Our results demonstrated that the indole alkaloid
      vallesiachotamine exhibited important cytotoxicity toward human melanoma cells
      and that apoptosis and necrosis might be responsible for the observed events.

PMID- 22477205
TI  - Improving working memory in children with attention-deficit/hyperactivity
      disorder: the separate and combined effects of incentives and stimulant
      medication.
AB  - Working memory (WM) is considered a core deficit in Attention-Deficit/
      Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM
      among children with ADHD. We tested the degree to which WM in children with ADHD
      was improved by performance-based incentives, an analog of behavioral
      intervention. In two studies, WM performance was assessed using a visuo-spatial n
      back task. Study 1 compared children (ages 9-12 years) with ADHD-Combined type (n
      = 24) to a group of typically developing (TD) children (n = 32). Study 1
      replicated WM deficits among children with ADHD. Incentives improved WM,
      particularly among children with ADHD. The provision of incentives reduced the
      ADHD-control group difference by approximately half but did not normalize WM.
      Study 2 examined the separate and combined effects of incentives and stimulant
      medication among 17 children with ADHD-Combined type. Both incentives and a
      moderate dose of long-acting methylphenidate (MPH; ~0.3 mg/kg t.i.d. equivalent)
      robustly improved WM relative to the no-incentive, placebo condition. The
      combination of incentives and medication improved WM significantly more than
      either incentives or MPH alone. These studies indicate that contingencies
      markedly improve WM among children with ADHD-Combined type, with effect sizes
      comparable to a moderate dose of stimulant medication. More broadly, this work
      calls attention to the role of motivation in studying cognitive deficits in ADHD
      and in testing multifactorial models of ADHD.

PMID- 22477206
TI  - Management of hypertension and factors affecting its control in Jordanian renal
      transplant recipients.
AB  - BACKGROUND: Hypertension affects 70-90 % of all kidney transplant recipients. It
      is associated with poor graft survival and is a contributing factor to the
      increased cardiovascular mortality. The reasons for the insufficient blood
      pressure control in transplanted patients have not been thoroughly investigated.
      OBJECTIVE: To evaluate the extent of blood pressure control in Jordanian
      hypertensive renal transplant recipients and to assess factors associated with
      such control. SETTING: Three outpatient renal transplant clinics in Amman.
      METHOD: A cross-sectional observational study including 181 patients. We have
      considered blood pressure <130/80 mm Hg as controlled hypertension. Bivariate and
      multivariate logistic regression analyses were used to determine clinical factors
      associated with achievement of blood pressure control. MAIN OUTCOME MEASURES:
      Proportion of patients who achieved hypertension control and clinical factors
      associated with good blood pressure control. RESULTS: Mean systolic blood
      pressure was 128.6 +/- 16.3 mm Hg and mean diastolic blood pressure was 82.8 +/-
      11.5 mm Hg. Blood pressure control was achieved only in 58 % of patients. The
      most commonly prescribed antihypertensives were calcium channel blockers (58 %)
      followed by beta-blockers (44 %). In bivariate analysis, female gender (p =
      0.017) and creatinine clearance (p = 0.002) were positively associated, while
      number of antihypertensive medications was inversely associated (p = 0.04) with
      achievement of blood pressure control. After including these factors in
      multivariate logistic regression analysis, only creatinine clearance remained
      independently associated with hypertension control (odds ratio, OR 1.04; 95 %
      confidence interval [CI] 1.01-1.06; p = 0.003). CONCLUSION: Blood pressure
      control among renal transplant recipients in Jordan was found to be inadequate.
      The only factor found to be independently associated with adequate blood pressure
      control was creatinine clearance.

PMID- 22477207
TI  - Primary coronary intervention versus thrombolytic therapy in myocardial
      infarction patients in the Middle East.
AB  - BACKGROUND: Little is known about predictors and outcome differences of primary
      percutaneous coronary intervention (PPCI) and thrombolytic therapy (TT) in ST
      segment elevation myocardial infarction (STEMI) patients in the Middle East.
      OBJECTIVE: To compare predictors as well as in-hospital outcomes of PPCI and TT
      in STEMI patients in six Middle Eastern countries. SETTING: Sixty-five hospitals
      (covering at least 85 % of the population) in Oman, United Arab Emirates, Qatar,
      Bahrain, Kuwait and Yemen. METHODS: This was a prospective, multinational,
      multicentre, observational survey of consecutive acute coronary syndrome patients
      who were admitted to 65 hospitals during May 8, 2006 to June 6, 2006 and from
      January 29, 2007 to June 29, 2007, as part of Gulf RACE (Registry of Acute
      Coronary Events). Analyses were performed using univariate and multivariate
      statistical techniques. MAIN OUTCOME MEASURES: Predictors as well as in-hospital
      outcomes of PPCI and TT in STEMI patients. RESULTS: Out of 2,155 STEMI patients
      admitted to hospitals within 12 h of symptoms onset, 92 % received reperfusion (8
      % PPCI and 84 % TT). TT use included reteplase (43 %), tenecteplase (30 %),
      streptokinase (25 %), and alteplase (2 %). Median age of the study cohort was 50
      (44-58) years with majority being males (90 %). There were no significant
      differences in median onset time to presentation between the TT and PPCI groups
      (130 vs. 120 min; P = 0.422). Median door-to-needle time and door-to-balloon time
      were 45 min (29-75) and 75 min (58-120), respectively. Predictors of PPCI
      included prior PCI, hospitals with catheterization laboratory facilities as well
      as those involved with academia. Multivariate logistic regression model
      demonstrated that patients that had PPCI were less likely to have recurrent
      ischemic attacks than those that had TT (odds ratio, 0.18; 95 % CI, 0.06-0.56; P
      = 0.003). CONCLUSIONS: The main reperfusion strategy for STEMI patients in the
      Arab Middle East region is thrombolytic therapy. Predictors of primary
      percutaneous coronary intervention included prior percutaneous coronary
      intervention, hospitals with catheterization laboratory facilities as well as
      those involved with academia. Primary percutaneous coronary intervention resulted
      in significant reductions in recurrent ischemic events when compared to
      thrombolytic therapy.

PMID- 22477208
TI  - Pharmaceutical care for people with depression: Belgian pharmacists' attitudes
      and perceived barriers.
AB  - BACKGROUND: In the past three decades, the role of pharmacists has evolved toward
      working with other health professionals and the public in a patient-centered
      model of practice, which is called pharmaceutical care. This model has been
      implemented for most physical illnesses but in relation to mental health,
      pharmacists' role is still evolving. OBJECTIVE: The objective of this study was
      to evaluate pharmacists' attitudes, current practice, perceived barriers and
      training needs concerning pharmaceutical care for people with depression.
      SETTING: All pharmacists attending obligatory regional meetings of the Surplus
      Network (a Flemish community pharmacy chain) during April and May 2009. METHOD:
      Written survey consisting of questions on (1) pharmacists' attitude and current
      practice in depression care and pharmaceutical care for people with other
      illnesses; (2) potential barriers in providing pharmaceutical care for people
      with depression; and (3) training needs. Paired samples T tests and Wilcoxon
      tests were used to analyze the data. MAIN OUTCOME MEASURE: Attitude and current
      practice in depression care versus care for other illnesses. RESULTS: Although
      the results show no difference in the attitude of pharmacists toward providing
      care for people with depression versus other illnesses (p = 0.315), pharmacists
      report to provide significantly less care to people with depression compared to
      people with other illnesses (p < 0.05). Perceived barriers toward providing
      depression care were the lack of information about the person and their
      treatment, the fact that depression is a difficult condition, the lack of
      education in mental health and the lack of time and privacy in the pharmacy.
      These, and the reported training needs, may limit the self-efficacy of
      pharmacists and hence influence current practice. CONCLUSION: In spite of
      pharmacists' positive attitude toward depression care, current practice displays
      actionable flaws. Barriers and training needs should be addressed in order to
      improve pharmaceutical care for people with depression.

PMID- 22477209
TI  - Editorial.

PMID- 22477210
TI  - Dedication: Ullin place: 1924-2000.

PMID- 22477212
TI  - Chomsky's nativism: A critical review.

PMID- 22477211
TI  - The Chomsky-Place correspondence 1993-1994.
AB  - Edited correspondence between Ullin T. Place and Noam Chomsky, which occurred in
      1993-1994, is presented. The principal topics are (a) deep versus surface
      structure; (b) computer modeling of the brain; (c) the evolutionary origins of
      language; (d) behaviorism; and (e) a dispositional account of language. This
      correspondence includes Chomsky's denial that he ever characterized deep
      structure as innate; Chomsky's critique of computer modeling (both traditional
      and connectionist) of the brain; Place's critique of Chomsky's alleged failure to
      provide an adequate account of the evolutionary origins of language, and
      Chomsky's response that such accounts are "pop-Darwinian fairy tales"; and
      Place's arguments for, and Chomsky's against, the relevance of behaviorism to
      linguistic theory, especially the relevance of a behavioral approach to language
      that is buttressed by a dispositional account of sentence construction.

PMID- 22477213
TI  - Chomsky's nativism reconsidered.

PMID- 22477214
TI  - A departure from cognitivism: Implications of Chomsky's second revolution in
      linguistics.
AB  - In 1957 Noam Chomsky published Syntactic Structures, expressing views
      characterized as constituting a "revolution" in linguistics. Chomsky proposed
      that the proper subject matter of linguistics is not the utterances of speakers,
      but what speakers and listeners know. To that end, he theorized that what they
      know is a system of rules that underlie actual performance. This theory became
      known as transformational grammar. In subsequent versions of this theory, rules
      continued to play a dominant role. However, in 1980 Chomsky began a second
      revolution by proposing the elimination of rules in a new theory: the principles
      and-parameters approach. Subsequent writings finalized the abandonment of rules.
      Given the centrality of rules to cognitivism, this paper argues that Chomsky's
      second revolution constitutes a departure from cognitivism.

PMID- 22477215
TI  - Effects of a stimulus-stimulus pairing procedure on conditioning vocal sounds as
      reinforcers.
AB  - Two experiments were conducted to investigate the effects of stimulus-stimulus
      pairing on conditioning vocal sounds as reinforcers. Four preschoolers with
      severe language and communication delays participated. In Experiment 1, an
      attempt was made to condition vocal sounds as a reinforcer by pairing a specific
      vocal sound with a reinforcing event (e.g., physical interaction). Results
      indicated that presentation of a stimulus-stimulus pairing was effective in
      conditioning the target vocal sounds as reinforcers, which increased the
      occurrence of vocalizations of those sounds by the participants. Experiment 2
      compared the effects of the pairing procedure with those of echoic training. The
      pairing procedure was identical to that in Experiment 1. In the echoic training
      condition, the experimenter produced the target vocal sound and gave the
      participant an opportunity to echo. The same reinforcing stimulus (e.g., physical
      interaction) was provided contingent upon the occurrence of the target vocal
      sound emitted by the participant. Results showed that the pairing procedure was
      more effective than the echoic training. Findings from this study suggest that
      for these participants, who had no vocal imitation skills, the stimulus-stimulus
      pairing was an effective procedure for conditioning vocal sounds as reinforcers
      and increased the probability of occurrence of the vocalization without a direct
      reinforcement contingency.

PMID- 22477216
TI  - Using intraverbal prompts to establish tacts for children with autism.
AB  - Some children with autism have difficulty acquiring tacts, despite their ability
      to mand, echo words, and imitate actions. The current study focused on 2 nonvocal
      children who had acquired a few mands using sign language, but had repeatedly
      failed to acquire signed tacts. Two procedures were compared to determine the
      most effective approach for training tacts to these participants. One procedure
      (the standard condition) used the general verbal prompt "What is that?" The other
      procedure (the intraverbal condition) used a specific intraverbal prompt "Sign
      [spoken word]." The results showed that both participants acquired nonimitative
      verbal responses during the intraverbal condition but not during the standard
      condition. One participant demonstrated complete transfer to pure tacts, and the
      other participant showed a partial transfer to pure tacts. These results have
      implications for the design of language intervention programs for children with
      autism who have difficulty acquiring tacts.

PMID- 22477217
TI  - Selection-based versus topography-based responding: An important distinction for
      stimulus equivalence?
AB  - English-speaking subjects were taught 16 English-French word pairs. Within any
      given trial, one word from each pair was presented; for eight items, subjects
      were to select its counterpart from an array of words in the other language
      (selection-based training), and for the other eight items there was no array and
      subjects were to type its counterpart (topography-based training). In Experiment
      1, all items were trained from French to English, and later, interspersed no
      feedback probe trials tested for the emergence of the reversed relations. Half of
      the eight selection-trained items were tested in the selection-based mode and
      half were tested in the topography-based mode; similarly, half of the eight
      topography-trained items were tested in the selection-based mode and half were
      tested in the topography-based mode. On the first reversal test trial, all 7
      subjects scored 100% correct for the selection-tested items; in contrast, 5 of
      the 7 subjects scored 0% or near 0% correct for the topography-tested items,
      which improved to varying degrees with repeated testing. The training response
      mode affected neither acquisition rate nor reversal test trial performance. In
      Experiment 2, all items were tested in the topography-based mode only, and
      subjects were exposed to nine consecutive reversal test trials prior to
      interspersed probe testing. Improved accuracy across reversal test trials was not
      observed until the conditions of probe testing were instated, an indication that
      reexposure to the trained relations was a crucial component of delayed emergence.
      In Experiment 3, all items were trained from English to French, resulting in
      subjects typing a familiar rather than an unfamiliar word on reversal test
      trials. Accuracy on reversal test trials was considerably better than in the
      previous two experiments. We discuss the implications of our findings for
      stimulus equivalence research.

PMID- 22477218
TI  - Verbal behavior and initial exposure to delayed reinforcement.
AB  - Ten subjects responded under a tandem fixed-ratio 1 not-responding-greater-than-t
      schedule of point delivery during one 75-min session in which the delay was
      either 10 or 20 s. Subjects were asked to describe the contingencies throughout
      the session. Although studies with non-humans have demonstrated response
      acquisition under similar delayed-consequence procedures, a minority of subjects
      in the current study demonstrated sensitivity to delayed consequences
      convincingly. All subjects exhibited inefficient patterns of responding and
      descriptions of nonexistent contingencies. Subjects who demonstrated learning
      were more likely to verbalize the actual contingencies, but this was not true in
      all cases. Furthermore, some subjects who demonstrated learning did not describe
      the delay contingency. Results suggest that learning may occur in the absence of
      a person's ability to describe environment-behavior relations.

PMID- 22477219
TI  - Words are not things.
AB  - On a traditional view, words are the fundamental units of verbal behavior. They
      are independent, autonomous things that symbolically represent or refer to other
      independent, autonomous things, often in some other dimension. Ascertaining what
      those other things are constitutes determining the meaning of a word. On a
      behavior-analytic view, verbal behavior is ongoing, functional operant activity
      occasioned by antecedent factors and reinforced by its consequences, particularly
      consequences that are mediated by other members of the same verbal community.
      Functional relations rather than structure select the response unit. The behavior
      analytic point of view clarifies such important contemporary issues in psychology
      as (a) the role of scientific theories and explanations, (b) educational
      practices, and (c) equivalence classes, so that there is no risk of strengthening
      the traditional view that words are things that symbolically represent other
      things.

PMID- 22477220
TI  - A contingency interpretation of Place's contingency anomaly in ordinary
      conversation.
AB  - A verbal phenomenon often reported in the research literature of conversation
      analysis is reviewed. The phenomenon involves the observation that spoken
      sentences often receive consequences from listeners, and that the effect of these
      consequences appears to be variability in sentence emission, whereas the absence
      of such consequences appears to produce response persistence. If the speaker's
      sentences function as units of verbal behavior and the listener's responses
      function as reinforcers, the effect seems to run contrary to reinforcement
      contingency effects observed in the laboratory, where reinforcement produces
      response differentiation and extinction produces an increase in response
      variability and a decrease in the response class previously selected by
      reinforcement. An interpretation of the conversation phenomenon is presented,
      employing standard reinforcement contingencies for which the behavioral dynamics
      involved may be seen when speaker's sequence of sentences is construed as a
      behavior chain.

PMID- 22477221
TI  - Publication trends in The Analysis of Verbal Behavior: 1982-1998.
AB  - Every article published in The Analysis of Verbal Behavior (TAVB) from its
      inception as a newsletter through 1998 was rated along several dimensions.
      Results indicated that the journal has grown substantially over time. Most
      articles (overall, 73%) published in TAVB did not describe experiments. The
      experiments that were described characteristically used within-subject designs
      and direct measures of behavior. They were conducted mostly by researchers in
      academic settings, using students as participants. Several authors have recently
      suggested that the journal should publish more experimental articles, covering a
      wider range of topics. The present results show that there is indeed room for
      more experimental articles, although they also underscore that the Journal has
      played, and continues to play, a major role as an outlet for both empirical and
      theoretical analyses of verbal behavior.

PMID- 22477222
TI  - Staffing the empirical analysis of verbal behavior.
AB  - Empirical articles in The Analysis of Verbal Behavior were inspected to evaluate
      the contributions of new and repeat investigators. The journal has attracted a
      steady stream of new empirical authors from early in its history. In recent
      years, repeat authors have begun to have a substantial impact on the journal.
      These outcomes suggest a maturing research community and provide cause for
      optimism about the future of empirical verbal behavior research.

PMID- 22477223
TI  - Whither the muse: What influences empirical research on verbal behavior?
AB  - To identify some of the published works that have helped to inspire empirical
      verbal behavior research, we searched for patterns in the sources cited in
      empirical studies published in The Analysis of Verbal Behavior between 1990 and
      1999. Not unexpectedly, Skinner's (1957) Verbal Behavior was the most cited
      source, although a variety of more recent sources explicating verbal relations as
      conceptualized by Skinner also were frequently cited. About one third of the most
      frequently cited sources were fairly recent primary empirical papers. These
      outcomes suggest that scholars who are interested in a behavior-analytic approach
      to studying verbal behavior are beginning to generate a critical mass of work
      that renders Verbal Behavior no longer monolithic in its influence. Nevertheless,
      some aspects of the citation data could be interpreted as evidence of insularity,
      and we argue for the importance of a broad-based analysis of verbal behavior that
      can have substantial impact outside of behavior analysis.

PMID- 22477224
TI  - The most important questions.

PMID- 22477225
TI  - The effects of a stimulus-stimulus pairing procedure on the vocal behavior of
      children diagnosed with autism.
AB  - Recent research suggests that the sound produced by a child's vocalization can
      become a conditioned reinforcer via the temporal pairing of an experimenter's
      vocal model with a preferred stimulus delivered to the child. The current study
      replicated and extended the findings of previous studies in this area. A multiple
      baseline design across vocal behaviors (combined with a reversal to baseline) was
      used to evaluate the effects of a stimulus-stimulus pairing procedure on one
      syllable utterances of 3 boys who had been diagnosed with autism. Data were
      collected during presession and postsession observations across four conditions:
      baseline, control, pairing, and reversal. During baseline, the free-operant
      levels of target sounds were recorded in the absence of experimenter interaction.
      During the control condition, the experimenter presented a vocal model and, after
      a 20-s delay, presented a preferred stimulus to the child. During the pairing
      condition, the experimenter's vocal model was paired with the delivery of the
      preferred item. Results from postsession observations during the pairing
      condition showed an increase in target sounds for 2 participants. This outcome
      may suggest that the children's vocalizations were automatically reinforced,
      albeit only temporarily. Practical and theoretical implications of the results
      are discussed along with the specific methods employed in this literature.

PMID- 22477226
TI  - Contriving establishing operations to teach mands for information.
AB  - Many children with autism cannot effectively ask wh- questions to mand for
      information, even though they may have extensive tact, intraverbal, and receptive
      language skills. Wh- questions are typically mands because they occur under the
      control of establishing operations (EOs) and result in specific reinforcement.
      The current study first investigated a procedure to teach the mand "where?" to
      children with autism by contriving an EO for the location of a missing item.
      Following the successful acquisition of this mand, an establishing operation for
      a specific person was contrived to teach the mand "who?" The results showed that
      the children acquired these mands when the relevant establishing operations were
      manipulated as independent variables. The children also demonstrated
      generalization to untrained items and to the natural environment. These results
      have implications for methods of language instruction for children who have
      difficulty acquiring mands for information.

PMID- 22477227
TI  - Altering the function of commands presented to boys with oppositional and
      hyperactive behavior.
AB  - Mentalistic and behavioral analyses of noncompliance among children with
      hyperactive behavior are contrasted. Then, a behavioral training program for 3
      boys with behavior characteristic of attention deficit hyperactivity disorder and
      oppositional defiant disorder is described. The child-focused training was
      conducted in conjunction with parent training. In an effort to increase the rate
      of compliance, the child-training program was designed to alter the function of
      parent commands by teaching the boys to verbalize rules about parent commands and
      consequences in the context of observing parent-child role-plays. Training was
      conducted within a multiple baseline design across children. Direct observation
      of mother-child interactions, telephone interviews, and standardized rating
      scales showed that training resulted in clinically significant reductions in
      noncompliance and improved parenting behavior. A 6-month follow-up revealed
      stable outcomes.

PMID- 22477228
TI  - The functional analysis of problematic verbal behavior.
AB  - This study describes procedures and outcomes in a functional analysis of problem
      behavior of 2 public school students. For a 13-year-old honors student, bizarre
      tacts (labeled as psychotic speech by school staff) were maintained by attention.
      For a 15-year-old with autism, the functional analysis revealed that
      perseverative mands for toileting were controlled by attention; mands for edible
      items were controlled by access to any food item; and mands for nonedible items
      were maintained by access to the specific item manded. The "problematic" aspects
      of the verbal behavior differed-the bizarre speech was problematic based on its
      content, but the perseverative verbalizations resulted in high response cost for
      classroom staff. Research in the area of problematic verbal behavior is sparse
      and warrants further attention from behavior analysts who work in public school
      settings. This research demonstrates the applicability and relevance of
      functionally analyzing problematic verbal behavior in public school settings.

PMID- 22477229
TI  - A comparison of textual and echoic prompts on the acquisition of intraverbal
      behavior in a six-year-old boy with autism.
AB  - A comparison of textual and echoic prompts was conducted to determine which form
      of prompts was more effective for teaching intraverbal behavior to a 6-year-old
      boy with autism. A multiple baseline design across three sets of questions
      measured (a) the number of full-sentence target answers, (b) partial answers that
      made sense, and (c) partial answers that did not make sense, or no response, to
      direct questions asked. A fading procedure using either scripted textual or
      scripted echoic prompts was employed to evoke the child's correct answers.
      Although both forms of prompts were effective, results indicated that textual
      prompts were much more effective. These findings suggest that textual prompts may
      be effective in teaching complex skills to children with autism.

PMID- 22477230
TI  - The selectionist meaning of C. S. Peirce and B. F. Skinner.
AB  - The selectionist meaning of C. S. Peirce and B. F. Skinner, which has an
      empirical existence, is advanced against essentialist meaning, which does not.
      Against a tradition that advocates essentialist meanings, the development of
      selectionist meaning is traced from Darwin through Peirce and on to Skinner. The
      views of Peirce and Skinner on meaning are presented as sharing a compatible
      conceptual foundation with contrasting but complementary distinctions. Support
      for selectionist meaning comes from contemporary dictionary construction,
      pragmatist philosophers, and recent views of scientific verbal behavior. Some
      implications are discussed.

PMID- 22477231
TI  - The functional analysis of psychological terms: The symmetry problem.
AB  - Skinner (1945) proposed an empirical research program in which subjective,
      mentalistic, or psychological terms from ordinary language could be analyzed in
      terms of the contingencies that control their occurrence. The practical successes
      of such a program, however, may face an unusual challenge. The symmetrical
      relation between the terms and the controlling contingencies may be construed by
      critics as support for the "intentional criticism," a frequent criticism of
      radical behaviorism by philosophers in which intentional concepts are said to
      "underlie" or are "presupposed" or are otherwise foundational to the technical
      vocabulary of behavior analysis. These critics thus promote intentional
      explanations as more fundamental and of more general importance than behavior
      analytic explanations of human behavior. A pragmatic counterargument is described
      in which the vocabulary of controlling contingencies enables uniquely effective
      behavior with respect to the phenomena that control the occurrence of the
      psychological term, unlike additional ordinary-language terms that might also be
      evoked by the term.

PMID- 22477232
TI  - The abative effect: A new term to describe the action of antecedents that reduce
      operant responding.
AB  - Behavior-analytic terminology concerning the so-called inhibitory effect of
      operant antecedents lacks precision. The present paper describes the problem with
      current nomenclature concerning the effects of antecedent events that reduce
      operant responding and offers a solution to this problem. The solution consists
      of adopting a new term, abative, for the effect in question. This paper suggests
      that the new term has several advantages over terms currently used and that
      adopting this term will yield a variety of practical and theoretical benefits,
      including, but not limited to, a more consistent vocabulary to describe
      antecedent-behavior relations.

PMID- 22477233
TI  - The psychological impact of a false-positive screening mammogram in Barcelona.
AB  - The purpose of this study was to ascertain the psychological impact of
      mammographic screening for women who receive negative results and for those who
      need additional non-invasive and invasive complementary investigations to exclude
      breast cancer (false positives). One hundred fifty women who attended a breast
      cancer screening programme in Barcelona, aged 50-69 years, were included in this
      study: 50 with negative results and 100 with false positive mammograms (50
      underwent non-invasive and 50 underwent invasive complementary investigations).
      Participants worried little until they underwent mammography, but worries
      increased when a telephone call notified the women of the need for further
      testing. A substantial proportion of women requiring further assessment reported
      that they were at least somewhat worried about having breast cancer throughout
      the screening process (P < 0.0001). Nevertheless, levels of anxiety and
      depression, measured by the Hospital Anxiety and Depression Scale, showed no
      statistically significant differences among the three groups. In conclusion,
      although the women showed no psychological morbidity, there is a substantial
      psychological response in those with an abnormal screening mammogram.

PMID- 22477234
TI  - Distinguishing factors for asymptomatic colonoscopy screening.
AB  - Demographic, medical history, physician factors, knowledge, beliefs and perceived
      barriers related to colorectal cancer (CRC) and CRC screening were compared for
      age-eligible individuals who received asymptomatic colonoscopy screening (n=100)
      versus those who did not receive any kind of CRC screening (n=142). All
      participants had health insurance that covered the full cost of colonoscopy
      screening. Screeners were more likely to have lower levels of income and
      education, to know the purpose of a colonoscopy, believe it was more normative,
      and report fewer barriers. Addressing these and other factors associated with CRC
      screening warrant testing as empirically based interventions.

PMID- 22477235
TI  - The development of a peritoneal surface malignancy program: a tale of three
      hospitals.
AB  - An increasing amount of evidence supports the use of cytoreductive surgery and
      heated intraperitoneal chemotherapy (HIPEC) for the treatment of select patients
      with carcinomatosis. The care of such patients is optimal at centers where
      physicians with expertise in the recognition, treatment, and follow-up of
      carcinomatosis collaborate to manage issues particular to patients undergoing
      HIPEC. New Peritoneal Surface Malignancy Programs should be introduced to meet
      the growing interest in this field; however, there are few guidelines available
      on how to propose, develop, and safely implement them across different hospital
      models. A new Peritoneal Surface Malignancy Program was initiated at a large
      academic medical center affiliated with three hospital systems serving distinct
      patient populations: a private hospital, a public hospital, and a Veterans
      Affairs hospital. Ten groups were identified as playing key roles in program
      implementation. Program approval was successfully obtained at all three
      hospitals. The initial two-year experience included a total of 20 cases across
      the three sites. Six of these cases were aborted due to high tumor volume, most
      of which (4/6) were at the public hospital. No 30-day mortalities occurred.
      Hospitals vary significantly in their approval process and timeline for new
      Peritoneal Surface Malignancy Program development. Patient populations differ in
      their awareness of HIPEC as a therapeutic modality. Public hospitals may serve
      patient populations with more advanced disease presentations. Careful
      coordination by the surgical oncologist with ten key groups allows for the safe
      introduction of a complex procedure within varied hospital models.

PMID- 22477236
TI  - University student understanding of cancer: analysis of ethnic group variances.
AB  - Traditional university and college students ages 18-24 are traversing an
      important period in their lives in which behavioral intervention is critical in
      reducing their risk of cancer in later years. The study's purpose was to
      determine the perceptions and level of knowledge about cancer of white, Hispanic,
      and black university students (n=958). Sources of student information about
      cancer were also identified. The survey results showed all students know very
      little about cancer and their perceptions of cancer are bad with many students
      thinking that cancer and death are synonymous. We also discovered university
      students do not discuss cancer often in their classrooms nor with their family or
      friends. Moreover, university students are unlikely to perform monthly or even
      yearly self-examinations for breast or testicular cancers; black students have
      the lowest rate of self-examinations.

PMID- 22477237
TI  - Reconsolidation from negative emotional pictures: is successful retrieval
      required?
AB  - Finn and Roediger (Psychological science 22:781-786, 2011) found that when a
      negative emotional picture was presented immediately after a successful
      retrieval, later test performance was enhanced as compared to when a neutral
      picture or a blank screen had been shown. This finding implicates the period
      immediately following retrieval as playing an important role in determining later
      retention via reconsolidation. In two new experiments, we investigated whether
      successful retrieval was required to show the enhancing effect of negative
      emotion on later recall. In both experiments, the participants studied Swahili
      English vocabulary pairs, took an intervening cued-recall test, and were given a
      final cued-recall test on all items. In Experiment 1, we tested a distinctiveness
      explanation of the effect. The results showed that neither presentation of a
      negative picture just prior to successful retrieval nor presentation of a
      positive picture after successful retrieval produced the enhancing effect that
      was seen when negative pictures were presented after successful retrieval. In
      Experiment 2, we tested whether the enhancing effect would occur when a negative
      picture followed an unsuccessful retrieval attempt with feedback, and a larger
      enhancement effect occurred after errors of commission than after errors of
      omission. These results indicate that effort in retrieving is critical to the
      enhancing effect shown with negative pictures; whether the target is produced by
      the participant or given by an external source following a commission error does
      not matter. We interpret these results as support for semantic enrichment as a
      key element in producing the enhancing effect of negative pictures that are
      presented after a retrieval attempt.

PMID- 22477238
TI  - Predicting and understanding undergraduate students' intentions to gamble in a
      casino using an extended model of the theory of reasoned action and the theory of
      planned behavior.
AB  - Given that current television programming contains numerous gambling portrayals,
      it is imperative to understand whether and to what extent these gambling
      behaviors in media influence individuals' beliefs, attitudes, and intentions.
      This study explores an extended model of the theory of reasoned action (TRA) by
      including gambling media exposure as a distal, mediating and mediated factor in
      predicting undergraduate students' intentions to gamble in a casino. Findings
      show that the extended model of TRA clearly indicates that the constructs of
      gambling media exposure, prior gambling experience, and level of gambling
      addiction contribute to the prediction of undergraduate students' casino gambling
      intentions. Theoretical implications of gambling media effects and practical
      implications for public policy are discussed, and future research directions are
      outlined.

PMID- 22477239
TI  - Eponyms in forensic pathology.
AB  - The phenomenon of eponymous terms in forensic pathology is described in this
      paper. The authors analyzed representative textbooks (monographs) dealing with
      forensic pathology in both English and German and identified several eponymous
      terms. The paper aims to present to the reader the most important eponymous terms
      in forensic pathology. Included in the paper are the following terms: Beckwith's
      Sign, Casper's Rule, Kronlein's Shot, Lichtenberg's Figures, Nysten's Law,
      Paltauf's Spots, Puppe's Rule, Sehrt's Sign, Simon's Sign, Sveshnikov's Sign,
      Tardieu's Spots, Wischnewski Spots, Wydler's Sign. The spread of eponymous terms
      throughout various languages is mentioned. The linguistic basis of such terms as
      well as their advantages and disadvantages in specialist fields, and indeed in
      even wider circles, is discussed. The authors state that the main function of
      these terms is to facilitate the open flow of unambiguous information among
      scholars. Eponymous terms in forensic pathology are characteristic for the German
      speaking countries and for all countries influenced by the German school of
      forensic pathology. Their usage in the Anglo-Saxon world is much less widespread,
      meaning they do not occur very often in English monographs and textbooks.

PMID- 22477240
TI  - Cryosurgery: A review.
AB  - Cryosurgery dates back to the 19th century, with the description of the benefits
      of local application of cooling for conditions such as pain control. Once
      commercial liquefied gases became available, more progress was made in the use of
      cryotherapy for localized lesions. As understanding of disease response to
      freezing increased, safer techniques for performing freezing procedures helped
      prepare its clinical application in different clinical situations, such as
      prostate disease and bronchial cancers. Cryosurgical techniques are less invasive
      and have lower morbidity compared with surgical resection. However, the use of
      cryosurgery has been limited by a lack of good understanding of the underlying
      mechanisms of tissue destruction. To apply cryosurgery clinically, and to extend
      its use, it is important to understand the mechanisms of freeze injury on cells,
      and to control the thermal parameters.

PMID- 22477241
TI  - Ozonized autohemotransfusion does not affect arterial vasodilation in patients
      with peripheral arterial disease.
AB  - Ozonized autohemotransfusion has been used as a complementary therapy in patients
      with peripheral arterial disease (PAD). To determine whether ozone therapy could
      acutely modify artery vasodilatory capacity, a flow-mediated dilation test was
      performed at the brachial artery level before and after an ozonized
      autohemotransfusion in 16 patients with PAD, mean (+/- SD) age 55+/-1.8 years,
      and 14 healthy volunteers matched for age, sex and body mass index. Before
      ozonized autohemotransfusion, the mean baseline diameter of the brachial artery
      was higher in PAD patients than in healthy subjects (4.6+/-0.54 mm versus 3.6+/
      0.54 mm, P<0.001) while mean flow-mediated brachial artery dilation and
      percentage of increase in flow were significantly lower in PAD patients than in
      controls (6.3+/-6.1% versus 11.8+/-2.4%, P<0.02; 433+/-61% versus 580+/-46%,
      P<0.02, respectively). No significant changes were observed after ozonized
      autohemotransfusion, indicating that ozonized autohemotransfusion does not modify
      endothelium-dependent ischemia-induced vascular reactivity.

PMID- 22477242
TI  - Coronary atherosclerosis, low-density lipoproteins and markers of thrombosis,
      inflammation and endothelial dysfunction.
AB  - Available information regarding the relation among atherosclerosis, low-density
      lipoproteins, markers of thrombosis, inflammation and endothelial dysfunction has
      accumulated, but is still very limited, making only minimal contributions to
      clinical decision-making. Many more clinical trials are needed, but unless there
      is a relationship between atherosclerosis prevention, specific markers and a
      pharmaceutical product, financial support for such trials will be difficult to
      obtain. The anti-inflammatory effect of statins is well established. Angiotensin
      converting enzyme inhibitors are generally not thought of as having anti
      inflammatory effects, but the European Trial on Reduction of Cardiac Events with
      Perindopril in Stable Coronary Artery Disease (EUROPA) study observed extensive
      RR reduction with perindopril. It was explained not simply by control of
      hypertension, but by reduced activity of multiple factors, supported by specific
      substudies. The 'cardiovascular continuum' is an excellent unifying term to
      explain atherosclerosis mechanisms, relate mechanisms to clinical understanding,
      and assist the clinician in selecting the appropriate prevention and control
      therapies. This so-called continuum actually describes a relationship among
      different biochemical, enzymatic and hormonal factors that affect the
      cardiovascular system. It can be seen in the downregulation of the angiotensin II
      receptor type 1 by statins, which contributes to hypertension control while
      lowering low-density lipoproteins. Peroxisome proliferator activator receptor
      gamma also demonstrates the cardiovascular continuum with activation of the
      receptor by glitazones. The glitazones increase insulin sensitivity for diabetes
      control. Activation of the peroxisome proliferator activator receptor-gamma
      inhibits inflammation, which is possibly related to atherosclerosis,
      normalization of endothelial function, suppression of metalloproteinases and a
      decrease in smooth muscle cell migration. All of these effects may decrease
      atherosclerosis production while improving control of diabetes mellitus, a key
      disease in the cardiovascular continuum for development of atherosclerosis.
      Consideration of such interrelationships is just scratching the surface.
      Nevertheless, it can be seen that the complicated process of atherosclerosis
      development has a multifaceted explanation that has been minimally defined, but
      holds the key to prevention and control of this major medical problem faced in
      modern society.

PMID- 22477243
TI  - Edaravone suppresses postoperative reperfusion injury in rat lower extremity: An
      immunohistological study.
AB  - PURPOSE: The present study evaluated whether the free radical scavenger edaravone
      (Radicut [Mitsubishi Pharma Co, Japan]) can suppress lower extremity
      postoperative reperfusion injury by evaluating muscle cell viability with
      immunohistological stain (cytochrome c oxidase stain). METHODS: Eight Lewis male
      rats (460 g to 510 g) were divided into two groups. In the control group,
      postoperative reperfusion injury models were created by clamping the bilateral
      common femoral arteries for 5 h and then releasing. In the other group, 9.0 mg/kg
      of edaravone was administered before clamping the bilateral common femoral
      arteries. After 5 h of reperfusion, the bilateral triceps muscles in both groups
      were stained with cytochrome c oxidase stain (each n=4 * 2). The positive areas
      of cytochrome c oxidase stain were measured and compared, using computerized
      densitometry (National Institutes of Health Image program, version 1.61).
      RESULTS: In the control group, the lower triceps muscles were not stained with
      cytochrome c oxidase. In the edaravone group, the lower triceps muscles were
      strongly stained with cytochrome c oxidase. The positive areas of cytochrome c
      oxidase stain were significantly greater in the edaravone group (133,000+/-12,000
      MU(2)/mm(2), P<0.01) compared with the control group (8000+/-1300 MU(2)/mm(2)).
      CONCLUSION: The present study suggests that the preoperative administration of
      9.0 mg/kg of edaravone may suppress postoperative reperfusion injury in a rat
      model.

PMID- 22477244
TI  - P-wave dispersion in patients with rheumatic mitral stenosis.
AB  - It has previously been shown that maximum P-wave duration and P-wave dispersion
      in 12-lead surface electrocardiogram (ECG) are significantly increased in
      patients prone to developing atrial fibrillation. Because patients with mitral
      stenosis (MS) are also susceptible to developing atrial fibrillation, the present
      study was carried out to determine whether maximum P-wave duration and P-wave
      dispersion are prolonged in MS patients during normal sinus rhythm. In addition,
      the correlation between these P-wave variables and the left atrial size,
      transmitral valve gradient and mitral valve area were determined. Fifty
      consecutive patients (40 women and 10 men; mean age 35.76+/-6.59 years) with MS
      who were in normal sinus rhythm, and a control group of 50 age- and sex-matched
      healthy persons were studied.A 12-lead ECG was obtained for each subject. All
      ECGs were scanned through a Cannon scanner at 300 dpi and saved as images in a
      personal computer. The minimum and maximum P-wave durations, as well as P-wave
      dispersion, were subsequently calculated. In addition, all patients were
      evaluated by echocardiography to measure the left atrial size, transmitral valve
      gradient and mitral valve area by planimetry. The P-wave parameters were compared
      between the two groups and the correlation between these parameters and the
      echocardiographic variables were determined in patients with MS. The most
      important findings included a significant prolongation of maximum P-wave duration
      in patients with MS compared with controls (P<0.001), and a strong correlation
      between the maximum P-wave duration and left atrial size (r=0.505, P<0.001),
      transmitral valve gradient (r=0.371, P=0.01) and a significant negative
      correlation with mitral valve area (r=-0.379, P=0.007). There was no correlation
      between the P-wave dispersion and echocardiographic parameters.

PMID- 22477245
TI  - Hemorrhagic shock secondary to rupture of a right gastroepiploic artery aneurysm:
      Case report and brief review of splanchnic artery aneurysms.
AB  - A case of a 78-year-old woman who presented with hemorrhagic shock and abdominal
      pain, and who was subsequently found to have a ruptured aneurysm of the right
      gastroepiploic artery, is presented. She underwent open surgical resection of the
      aneurysm without any significant postoperative complication. A brief review of
      splanchnic artery aneurysms with regard to their incidence, presentation and
      approaches for repair is also presented.

PMID- 22477246
TI  - Impact of a bidirectional approach via radial and popliteal arteries for the
      treatment of chronic total occlusion of lower limb artery: A case report.
AB  - A 49-year-old man with poorly controlled diabetes was admitted to Kushiro Rosai
      Hospital, Hokkaido, Japan after scalding both feet with boiling water. Because of
      poor healing, he was assessed for peripheral arterial disease. Angiography
      revealed total occlusion of the right common and external iliac arteries, diffuse
      stenosis of the right superficial femoral artery, focal stenosis of the left
      common iliac artery and chronic total occlusion of the left superficial femoral
      artery. A staged procedure with bidirectional approach via the radial and
      popliteal arteries was attempted. During the procedures, the patient was in the
      prone position on the catheterization table, and bidirectional guidewire
      manipulation was performed. All of the lesions were successfully stented. The
      patient was not required to change positions during the procedure, which can be
      performed by a single operator. The bidirectional approach is effective in the
      setting of transcatheter treatment of chronic total occlusive disease.

PMID- 22477247
TI  - Treatment of a coronary artery aneurysm by use of a covered stent graft - a case
      report.
AB  - Coronary artery aneurysm is a rare finding at coronary angiography. Most coronary
      aneurysms remain asymptomatic. There is no consensus on its management; some
      advocate aggressive approach while others advocate conservative management. A
      case of coronary artery aneurysm successfully treated by implantation of a
      polytetrafluoroethylene-covered coronary stent is presented.

PMID- 22477248
TI  - Primary percutaneous coronary intervention of an anomalous right coronary artery
      arising from the left coronary cusp using an undersized Judkins catheter: A case
      report.
AB  - Occlusion of an anomalous right coronary artery arising from the left coronary
      cusp is a rare cause of acute inferior wall myocardial infarction. The case of a
      66-year-old man who presented with an acute inferior wall myocardial infarction
      from occlusion of an anomalous right coronary artery arising from the left
      coronary cusp is described. An undersized Judkins left guide catheter was
      successfully used to perform primary percutaneous coronary intervention for this
      anomaly. Computed tomographic angiography was subsequently used to characterize
      the origin and anatomical course of the anomalous right coronary artery and
      assess coronary stent patency.

PMID- 22477249
TI  - Questions and complexities.

PMID- 22477250
TI  - Alternative theories of the origin of derived stimulus relations.
AB  - Two theories of derived stimulus relations are discussed. Sidman's primary
      process theory holds that contingencies establish the discriminative stimulus,
      the response, and the reinforcement as members of the same equivalence class.
      This position suggests a continuity of processes between humans and nonhumans and
      requires only a very modest change in traditional views concerning principles of
      behavior. Hayes, Barnes-Holmes and Roche also maintain that equivalence is a
      function of contingencies. However, they maintain that equivalence is only one of
      many relational frames that are developed through learning multiple examples.
      Moreover, once relational frames are developed, these frames may change the
      effects of direct contingencies. They state that if their position is valid "we
      must rethink all of behavioral psychology as it applies to verbal organisms."
      Their position implies a discontinuity between the behavior of humans and
      nonhumans. These two different perspectives suggest quite different research
      agendas. The research agenda suggested by Hayes et al. is primarily directed
      toward the study of human behavior, while the research agenda of Sidman suggests
      the study of both human and nonhuman behavior.

PMID- 22477251
TI  - On the verbal behavior of relational frame theory: A post-skinnerian account of
      human language and cognition.
AB  - The authors of the provocative subtitle, without embarrassment, set out to
      produce a revolution in the behavioral study of verbal behavior. I first consider
      their new definition and then suggest avoiding the definitional problem by
      describing the properties that characterize verbal behavior, including both those
      that are like nonverbal behavior and those that are unlike it. Conceding that
      this book is not an easy read, I nevertheless conclude that we all examine its
      assertions in detail and in research.

PMID- 22477252
TI  - Behavior analysis and linguistic productivity.
AB  - The greatest intellectual challenge to the field of behavior analysis may be
      understanding linguistic productivity (e.g., being able to correctly say and
      understand novel sentences). One of the main issues concerning linguistic
      productivity is whether behavioral productivity is, itself, a fundamental
      behavioral process, as claimed by the proponents of relational frame theory, or
      whether we can understand linguistic productivity in terms of more fundamental
      behavioral principles.

PMID- 22477253
TI  - Beyond Skinner? A review of relational frame theory: A post-skinnerian account of
      human language and cognition by Hayes, Barnes-Holmes, and Roche.
AB  - In their book, Relational Frame Theory: A Post-Skinnerian Account of Human
      Language and Cognition (2001), Hayes, Barnes-Holmes and Roche challenge behavior
      analysts to put aside Skinner and Verbal Behavior in favor of relational frame
      theory's approach to human language and cognition. However, when viewed from the
      contexts of behavior analysis, the principles of behavior analysis, and the
      principles of the founder of behavior analysis, Relational Frame Theory fits
      squarely in the Skinnerian, behavior analytic tradition. As with Verbal Behavior,
      Relational Frame Theory and its theses may be thought of as logical and empirical
      extensions of that which precedes them.

PMID- 22477254
TI  - A stimulus in need of a response: A review of relational frame theory: A post
      skinnerian account of human language and cognition.
AB  - In this commentary, I describe relational frame theory (RFT) as an analysis of
      complex human behavior that has been insufficiently addressed within contemporary
      behavior analysis. The theory is described as having an exceptionally ambitious
      vision of the type that will render behavior analytic accounts more generally
      acceptable within the broader behavioral and cognitive sciences. In my own view,
      inductive empirically-driven analyses derived from current data on relational
      learning (including my own) have not been comparably ambitious; they have not
      addressed the full range of phenomena to which they might be profitably applied.
      By contrast, researchers in the RFT tradition have ambitious; they have not
      addressed the full range of phenomena to which they might be profitably applied.
      By contrast, researchers in the RFT tradition have tended to project their
      analyses to encompass a variety of plausible, attractive applications that are
      arguably within the reach of their current data or data that may be reasonably
      anticipated in the future. In order for RFT researchers to have its maximum
      impact, however, I suggest that certain critical steps must be accomplished.
      First, the theory must be reconciled with the basic behavioral processes that are
      the core of the experimental analysis of behavior. Second, certain experiments
      must be conducted that have thus far not been emphasized in the RFT tradition. In
      particular, I suggest that the current practice of studying college students and
      verbal school-aged children must be supplemented with comparably intensive
      studies of populations with developmental limitations (e.g., typically developing
      children who are just acquiring language). Absent such experimentation, it seems
      likely that RFT will remain a plausible account that merely competes with other
      plausible accounts without promoting ultimate resolution of the critical issues.

PMID- 22477255
TI  - Behavior analysis, relational frame theory, and the challenge of human language
      and cognition: A reply to the commentaries on relational frame theory: A post
      skinnerian account of human language and cognition.
AB  - Answers to a series of commentaries are presented and the challenge Relational
      Frame Theory (RFT) presents to behavior analysis is explicated. RFT is a behavior
      analytic theory, based on extensive behavior analytic data, which appeals only to
      known principles to explain arbitrarily applicable relational responding. The
      claim that such responding is operant must be answerable within behavior
      analysis. RFT has too much empirical support for the field to avoid this
      challenge. If the answer is "yes," behavior analysis seems destined to enter a
      new era.

PMID- 22477256
TI  - Predicting taxonomic and thematic relational responding.
AB  - Pairs of pictures were classified by the authors and others as related by
      identity (A-A), basic taxonomy (A-B), superordinate taxonomy (A-C), or by theme
      (A-D). Two-choice matching-to-sample trial types were composed of these same
      picture pairs in which the sample was common to the two stimulus pairs in each
      configuration and, together with the sample, each comparison exemplified one of
      the relations in the picture pair; that is: A(AB), A(AC), A(AD), A(BC), A(BD),
      and A(CD). In five experiments, for each picture pair, college students
      classified the relation (as taxonomic or thematic) and rated its strength (Exps
      1, 3) or its similarity (Exp 4); others matched to sample the foregoing trial
      types only (Exps 2, 5), or they classified and rated, too (Exp 3). With
      exceptions, students classed most pairs as the authors did. They also
      collectively ordered relational strengths from (1) identity, (2) basic taxonomy,
      and (3) theme, to (4) superordinate taxonomy based, in part, on the similarity of
      sample and comparison. Subjects chose the comparisons of the more strongly
      related picture pairs in the matching-to-sample task on 90 percent or more of the
      configurations. Subjects' selections in two-choice, matching-to-sample
      configurations using natural stimuli may be based on existing stimulus control
      topographies such as those exhibited by ratings of the relations in a
      configuration.

PMID- 22477257
TI  - The hierarchical relationship between several visual and auditory discriminations
      and three verbal operants among individuals with developmental disabilities.
AB  - This study examined the relationship between performance on the Assessment of
      Basic Learning Abilities test (ABLA), two auditory matching tasks, and a test of
      echoics, tacts, and mands with persons with developmental disabilities. It was
      found that discrimination skill (visual, auditory-visual, and auditory-auditory
      discriminations) was a better predictor of performance on verbal operant
      assessments than level of functioning based on diagnosis. The results showed high
      test-retest reliability for the test of verbal operants and no hierarchical
      relationship was found among the three verbal operants. The results suggest that
      the ABLA Level 6 might be a possible bridging task for teaching echoics, tacts,
      and mands. Further research is needed to ascertain the relation between the
      auditory matching tasks and the verbal operants.

PMID- 22477258
TI  - Michael and Malott's dialog on linguistic productivity.
AB  - This is an informal dialog between Jack Michael and Dick Malott inspired by
      Malott's commentary (In press) on Relational Frame Theory: A Post-Skinnerian
      Account of Human Language and Cognition (Hayes, Barnes-Holmes, Roche; 2001).
      Topics range from psychologist Skinner to linguist Hockett and from the Skinner
      box to verbal behavior (AKA language).

PMID- 22477259
TI  - Intracellular accumulation of aggregated pyroglutamate amyloid beta: convergence
      of aging and Abeta pathology at the lysosome.
AB  - Deposition of aggregated amyloid beta (Abeta) is a major hallmark of Alzheimer's
      disease (AD)-a common age-related neurodegenerative disorder. Typically, Abeta is
      generated as a peptide of varying lengths. However, a major fraction of Abeta
      peptides in the brains of AD patients has undergone posttranslational
      modifications, which often radically change the properties of the peptides.
      Abeta3(pE)-42 is an N-truncated, pyroglutamate-modified variant that is
      abundantly present in AD brain and was suggested to play a role early in the
      pathogenesis. Here we show that intracellular accumulation of oligomeric
      aggregates of Abeta3(pE)-42 results in loss of lysosomal integrity. Using a novel
      antibody specific for aggregates of AbetapE3, we show that in postmortem human
      brain tissue, aggregated AbetapE3 is predominantly found in the lysosomes of both
      neurons and glial cells. Our data further demonstrate that AbetapE3 is relatively
      resistant to lysosomal degradation, which may explain its accumulation in the
      lysosomes. The intracellular AbetapE3 aggregates increase in an age-dependent
      manner. The results presented in this study support a model where Abeta pathology
      and aging converge, leading to accumulation of the degradation-resistant pE
      modified Abeta in the lysosomes, lysosomal dysfunction, and neurodegeneration.

PMID- 22477261
TI  - Evaluation of sequential FDG-PET/CT for monitoring bone metastasis of breast
      cancer during therapy: correlation between morphological and metabolic changes
      with tumor markers.
AB  - PURPOSE: The purpose of this study was to clarify the significance of positron
      emission tomography (PET) and computed tomography (CT) findings for evaluating
      the bone metastasis of breast cancer during therapy. PATIENTS AND METHODS: Forty
      seven patients with bone metastases from breast cancer who underwent sequential
      FDG-PET/CT studies during therapy were enrolled. A total of 771 lesions were
      identified. The changes in the PET and CT findings were compared with the tumor
      marker levels in each patient by calculating the weighted kappa value. The
      correlation between the PET and CT findings was examined for each lesion by an
      adjusted Chi-square test. RESULTS: The change in the tumor marker levels was
      substantially correlated with the PET findings and moderately correlated with the
      CT findings (weighted kappa = 0.780 and 0.585 for quadratic weighting,
      respectively). An increase in FDG uptake was correlated with lytic changes on the
      CT images (62/65, 95.4 %, p < 0.05). Sclerotic changes suggested improvement, but
      sclerosis and progression occurred at the same time in some lesions. CONCLUSION:
      Changes of FDG uptake are useful for evaluating individual bone metastases in
      cases of breast cancer during therapy. Lytic change on CT images suggests
      progression of bone metastasis. The lysis-progression/sclerosis-improvement
      pattern was observed in the majority of subjects, but a sclerosis-progression
      pattern was also observed. The hybrid pattern of increase of FDG uptake on
      PET/lytic change on CT is most accurate to show progression of bone metastases.
      Assessments of these processes during therapy are necessary for the precise
      evaluation of bone metastases.

PMID- 22477260
TI  - The NPY system and its neural and neuroendocrine regulation of bone.
AB  - The past decade has seen a significant expansion of our understanding of the
      interaction between the neural system and bone. While innervation of bone was
      long appreciated, the discovery of central relays from the hypothalamus to the
      cells of bone has seen the identification of a number of efferent neural pathways
      to bone. The neuropeptide Y (NPY) system has proven to represent a major central
      pathway, regulating the activity of osteoblasts and osteoclasts, through
      signaling of central and peripheral ligands, through specific receptors within
      the hypothalamus and the osteoblast. Moreover, this pathway is now recognized as
      acting to coordinate both skeletal and energy homeostasis. This review examines
      the mechanism and actions of the NPY pathway to regulate bone mass and bone cell
      activity.

PMID- 22477262
TI  - 18F-FLT PET performs better than 18F-FDG PET in differentiating malignant uterine
      corpus tumors from benign leiomyoma.
AB  - PURPOSE: The aim of this study is to test the hypothesis that positron emission
      tomography (PET) with 3'-deoxy-3'-[(18)F]-fluorothymidine ((18)F-FLT) can
      differentiate malignancy from benign leiomyoma better than PET with 2-deoxy-2
      [(18)F]fluoro-D-glucose ((18)F-FDG), and to evaluate whether (18)F-FLT and (18)F
      FDG uptake correlate with immunohistochemical index of cell proliferation.
      METHODS: The protocol of this prospective study was approved by the institutional
      ethics committee, and all patients gave written informed consent. Fifteen
      patients (aged 26-65 years, median 44 years) with uterine corpus tumor which has
      the possibility of being leiomyosarcoma underwent (18)F-FLT and (18)F-FDG PET
      scans. Maximum standard uptake value (SUV(max)) of PET scans and Ki-67 labeling
      index of surgical specimens were evaluated. Mann-Whitney's U test was used for
      comparing uptakes between benign and malignant, and linear regression analysis
      was used for evaluating the correlation between Ki-67 labeling index and
      SUV(max). RESULTS: Five cases were diagnosed as malignant (leiomyosarcoma for 3
      cases, and carcinoma for 2 cases), and the others were benign leiomyoma.
      Sensitivity and negative predictive value of both tracers for detecting
      malignancy was 100%. Specificity, positive predictive value and accuracy of (18)F
      FLT PET were higher than those of (18)F-FDG PET. Difference in SUV(max) between
      malignant and benign was significant for (18)F-FLT PET (P < 0.01), but not for
      (18)F-FDG PET. While all the malignant cases showed positive uptake in both
      tracers, a case of leiomyosarcoma with huge necrosis showed relatively low
      uptake. Uptake of (18)F-FLT showed better correlation with Ki-67 labeling index
      compared with (18)F-FDG (R(2) = 0.91 vs. R(2) = 0.26). CONCLUSION: Negative
      findings on additional (18)F-FDG or (18)F-FLT PET may rule out the possibility of
      malignancy for the patients with suspected leiomyosarcoma diagnosed by
      conventional methods. (18)F-FLT PET is superior to (18)F-FDG PET in
      differentiating malignant from benign leiomyoma. Moreover, (18)F-FLT uptake
      correlated well with the immunohistochemical index of cell proliferation.

PMID- 22477263
TI  - EORTC QLQ-BM22 and QLQ-C30 quality of life scores in patients with painful bone
      metastases of prostate cancer treated with strontium-89 radionuclide therapy.
AB  - PURPOSE: Approximately 80% of patients with prostate cancer will develop bone
      metastases, which often lead to bone pain and skeletal-related events. Sr-89 is
      an established alternative for the palliation of bone pain in prostate cancer. We
      aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL)
      in prostate cancer patients with painful bone metastases. MATERIALS AND METHODS:
      Thirteen patients received a single intravenous injection of Sr-89 at a dose of
      2.0 MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1,
      2, and 3 months afterward using the Japanese version of the EORTC QLQ-BM22, EORTC
      QLQ-C30, a VAS, and face scale. We also evaluated PSA and ALP response and
      toxicity of the Sr-89 therapy. RESULTS: The pain characteristics subscale of the
      EORTC QLQ-BM22 was significantly reduced from 1 month onward compared with the
      baseline. The functional interference and psychosocial aspects subscales were
      significantly higher than baseline from 2 months onward. At 2 months, VAS
      indicated a significant reduction in pain as compared to the baseline. Sr-89
      therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had
      leukocyte toxicity, and one patient had grade 3 platelet toxicity. CONCLUSION: Sr
      89 radionuclide therapy can provide not only reduced pain characteristics but
      also better psychosocial aspects and functional interference in patients with
      painful bone metastases of prostate cancer.

PMID- 22477264
TI  - Cosmetic evaluation following volume replacement using lateral tissue flap in
      breast-conserving surgery.
AB  - BACKGROUND: We examined the effectiveness of volume replacement using a lateral
      tissue flap (LTF) in breast-conserving surgery for a good cosmetic outcome.
      METHODS: We analyzed the results of 130 patients with breast cancer who underwent
      breast-conserving surgery with replacement using an LTF from 2006 to 2010 with
      cosmetic evaluations performed according to the criteria of the Japanese Breast
      Cancer Society. We examined scores with regard to the following possible
      contributing factors: partial resection (Bp) or quadrantectomy (Bq), diameter of
      the specimen, body mass index (BMI), axillary lymphadenectomy, postoperative
      irradiation, and position of the tumor. RESULTS: The scores for cases with Bp and
      non-postoperative irradiation were higher than those for Bq and postoperative
      irradiation cases, though they were not significant factors in multivariate
      analysis. A negative correlation was seen between score and diameter of the
      specimen, whereas there was no significant correlation with BMI. There was no
      significant difference between scores of cases with or without an axillary
      lymphadenectomy. However, the score for the extended upper-outer area including
      the upper and outer borders was significantly higher than scores for other
      portions. In multiple regression analysis, cases with a tumor diameter less than
      4 cm in the extended upper-outer area or less than 2 cm in other areas showed
      good adaptation. CONCLUSION: Tumor location and diameter are important factors
      for cosmetic evaluation of volume replacement using an LTF.

PMID- 22477265
TI  - Prognostic factors for survival after first recurrence in breast cancer: a
      retrospective analysis of 252 recurrent cases at a single institution.
AB  - INTRODUCTION: Previous studies have shown that primary breast cancer patients
      with estrogen receptor (ER)-positive status have better outcomes in terms of both
      overall survival and disease-free intervals (DFI). However, 25.2 % of our ER
      positive patients experienced recurrence. This study aimed to define factors
      potentially predicting survival after first recurrence in surgically treated
      patients with stage I-III breast cancer. METHODS: We retrospectively analyzed 252
      females with recurrent breast cancer who had undergone surgery and been followed
      at Kyoto University Hospital in Japan. Age, clinical stage, pathological stage,
      axillary lymph node involvement, ER status at the time of diagnosis, progesterone
      receptor status, human epidermal growth factor receptor 2 status, operative
      method, adjuvant chemotherapy, adjuvant endocrine therapy, use of trastuzumab
      after recurrence, site of recurrence, DFI, and time of recurrence were examined
      for possible influences on survival after the first recurrence. RESULTS: Positive
      ER status and positive PR status at the time of diagnosis were significantly
      favorable factors of survival after first recurrence for patients with
      recurrence, p < 0.001 and p = 0.021, respectively. More than two sites of
      recurrence (p < 0.001) were associated with shorter survival time after the first
      recurrence on multivariate analysis. Survival of patients with recurrent breast
      cancer steadily improved from 1980-1994 to 1995-2008, significantly in ER
      negative subgroups. CONCLUSIONS: Positive ER status at the time of diagnosis is a
      powerful predictor for favorable survival after first recurrence. Survival time
      after first recurrence of breast cancer has steadily increased in recent decades.
      Advances in treatments and attitudes about breast cancer have contributed to this
      improvement in survival after first recurrence.

PMID- 22477266
TI  - Breast biopsy for mammographically detected nonpalpable lesions using a vacuum
      assisted biopsy device (Mammotome) and upright-type stereotactic mammography unit
      without a digital imaging system: experience of 500 biopsies.
AB  - BACKGROUND: The most common diagnostic procedure in the United States for
      mammographically detected nonpalpable lesions is a combination of a vacuum
      assisted biopsy device and a prone-type biopsy table. We have used an upright
      type stereotactic mammography unit without a digital imaging system instead of
      the prone table. PATIENTS AND METHODS: Five-hundred ten biopsies of 506
      mammographically detected nonpalpable breast lesions in 488 patients, consisting
      of 445 lesions with microcalcifications alone, 39 masses without calcifications,
      and 22 with both masses and microcalcifications, were attempted using a
      combination of a vacuum-assisted device (Mammotome) and an upright unit without a
      digital imaging system in a sitting position between May 1999 and February 2007.
      RESULTS: Breast tissue was obtained in 497 biopsies. Microcalcifications were
      confirmed radiographically in the tissue of 447 out of 459 biopsies from lesions
      with microcalcifications (97.4 %). One hundred thirty-seven were diagnosed as
      malignant, 10 as atypical ductal hyperplasia, 345 as benign, and 1 was not
      diagnosable. The underestimation rate was 28.0 %. Overall, 26 patients (5.1 %)
      had vasovagal reactions, while 19 (3.8 %) experienced mild subcutaneous bleeding.
      Two hundred fifty of 350 lesions, for which biopsy diagnoses were benign, were
      followed for a median period of 33 months. Four lesions turned out to be
      malignant. The false-negative rate was 2.8 %. CONCLUSION: The biopsy technique
      using the combination of the Mammotome and an upright unit without a digital
      imaging system is cost-effective, safe, and accurate, and should be regarded as
      one of the standard biopsy methods for mammographically detected nonpalpable
      lesions.

PMID- 22477267
TI  - Underestimation of papillary breast lesions by core biopsy: correlation to
      surgical excision.
AB  - BACKGROUND: The purpose of this study was to evaluate papillary lesions of the
      breast diagnosed at needle core biopsy and the outcomes of follow-up imaging and
      surgical findings. METHODS: Retrospective review of 13,806 needle core biopsies
      performed from 2004 to 2010 revealed 352 patients with 368 papillary lesions; 137
      of these lesions underwent surgical excision and 215 had a minimum of 2 year
      imaging follow-up. Outcomes of imaging follow-up and underestimation of carcinoma
      by comparison to surgical excision, as applicable, were determined. Patient
      demographics, clinical presentation, BI-RADS((r)) breast density, palpability,
      biopsy methods, number of specimens, and pathology were recorded. A two-tailed
      Fisher exact test was used to assess associations between biopsy techniques and
      the results of surgical excision as well as the association between palpability
      and the results of surgical excision. SAS((r)) V 9.1.3 was used to perform the
      calculations. RESULTS: One hundred and thirty-seven lesions proceeded to surgical
      excision. A total of 28 lesions were underestimated; 21 of these were
      underestimated carcinomas. When comparing biopsy devices in the underestimated
      group, 64 % were biopsied with directional vacuum-assisted devices and 36 % with
      automated large core devices (p < 0.0706). In total 18 % of the palpable lesions
      were underestimated, whereas 17 % of the nonpalpable lesions were underestimated
      (p < 0.6560); this was not a significant difference. CONCLUSIONS: Overall,
      carcinoma was underestimated at needle biopsy in 6 % (21/368) of papillary
      lesions diagnosed when compared to surgical excision. In cases that underwent
      excision, 34 % (47/137) revealed carcinoma; 45 % (21/47) of these were
      underestimated carcinomas. Lesion palpability and biopsy method did not affect
      underestimation in this study population.

PMID- 22477269
TI  - Patients with echocardiographic aortic valve calcium or mitral annular calcium
      have an increased prevalence of moderate or severe coronary artery calcium
      diagnosed by cardiac computed tomography.
AB  - The association between aortic valve calcium (AVC) and mitral annular calcium
      (MAC), as diagnosed by two-dimensional echocardiography, was investigated in 138
      patients (76 women and 62 men, mean age 64+/-8 years) seen in a private
      cardiology practice at the New York Medical College. Coronary artery calcium
      (CAC) scores were diagnosed by 64-multislice computed tomography. AVC was present
      in 25 of 57 patients (44%) with moderate or severe CAC (a CAC score of more than
      100) and in 15 of 81 patients (19%) with no or mild CAC (a CAC score of 0 to
      100), P<0.001. Moderate or severe AVC was present in nine of 57 patients (16%)
      with moderate or severe CAC, and in two of 81 patients (2%) with no or mild CAC,
      P<0.005. MAC was present in 18 of 57 patients (32%) with moderate or severe CAC,
      and in seven of 81 patients (9%) with no or mild CAC, P<0.001. Moderate or severe
      MAC was present in eight of 57 patients (14%) with moderate or severe CAC, and in
      two of 81 patients (2%) with no or mild CAC, P<0.001.

PMID- 22477270
TI  - Percutaneous transluminal angioplasty of the popliteal artery without the use of
      stents: A review of 116 consecutive procedures.
AB  - PURPOSE: To evaluate the safety and efficacy of percutaneous transluminal
      angioplasty (PTA), without the use of stents, for the treatment of popliteal
      artery stenosis. METHODS: From March 1997 to December 2003, 116 consecutive PTAs
      of the popliteal artery were performed in 98 patients. All patients underwent
      preoperative and postoperative colour duplex scans and preoperative angiography.
      In all cases, the superficial femoral artery was patent and without significant
      stenosis. Follow-up patency was assessed by clinical examination and colour
      duplex scanning in all patients. RESULTS: There was no perioperative mortality.
      Primary patency after two years was 86% for intermittent claudication (IC)
      patients and 54% for critical limb ischemia (CLI) patients. Secondary patency
      rates were 98% for IC patients versus 92% for CLI patients after one year, 94%
      for IC patients versus 83% for CLI patients after two years and 69% for IC
      patients versus 7% for CLI patients after five years (P<0.001). CONCLUSION:
      Popliteal artery PTA is safe and efficient, especially in IC patients with single
      lesions.

PMID- 22477268
TI  - Peripheral arterial disease: Epidemiology, natural history, diagnosis and
      treatment.
AB  - Lower extremity peripheral arterial disease (PAD) affects approximately 10% of
      the American population, with 30% to 40% of these patients presenting with
      claudication symptoms. The prevalence of PAD increases with age and the number of
      vascular risk factors. More importantly, it is a marker of atherosclerotic
      disease burden, and is associated with increased mortality from cardiovascular
      and cerebrovascular causes. There have been recent advances in noninvasive
      imaging, endovascular approaches for revascularization, and aggressive risk
      factor management for prevention of cardiac and cerebrovascular complications in
      PAD. There is now a trend toward aggressive risk factor modification and
      endovascular revascularization for most patients, with surgical interventions
      reserved for certain situations only. In the present article, a systematic review
      is presented, focusing on the key aspects of the disease epidemiology,
      presentation, natural history, diagnosis and available management options.

PMID- 22477271
TI  - Earliest time of change in QT dispersion after stenting in patients with single
      vessel coronary artery disease.
AB  - Dispersion of the QT interval (QTd) is a measure of inhomogeneity of ventricular
      repolarization, and its prolongation may provide a suitable substrate for life
      threatening ventricular arrhythmias. The present study was performed to determine
      the onset time of change in the corrected QT (QTc) interval and QTd in patients
      with stable angina and single vessel coronary artery disease. Electrocardiograms
      of 60 patients with successful stenting, obtained 1 h before and 1 h, 6 h, 12 h
      and 24 h after the procedure were analyzed. The QTc interval, QTc maximum, QTc
      minimum and QTd were measured. All electrocardiograms were scanned, and then
      underwent computer-based analysis. There was a significant reduction in the mean
      QTc interval as early as 12 h after the procedure (from 474+/-41 ms to 460+/-31
      ms; P<0.001), which persisted to the 24 h follow-up. This was associated with a
      significant reduction in mean QT maximum (from 496+/-31 ms to 418+/-66 ms;
      P<0.001) and a significant prolongation in mean QT minimum (from 403+/-21 ms to
      444+/-12 ms; P<0.001) at the same time intervals. Therefore, successful stenting
      of coronary arteries in patients with single vessel coronary artery disease and
      stable angina decreases QTd as early as 12 h after the procedure. This phenomenon
      may be the result of improved regional myocardial circulation, and reduced
      ischemia. A persistently low QTd in the following months may therefore have
      prognostic significance, and can be used as a noninvasive marker of stent
      patency. Further studies are necessary to define the clinical applicability of
      QTd in the assessment of long-term stent patency in such patients.

PMID- 22477272
TI  - A review of troponins in ischemic heart disease and other conditions.
AB  - Measuring cardiac troponin (cTn) I and T levels is currently considered to be a
      cornerstone for making the diagnosis of acute coronary syndrome (ACS).Based on
      current literature, cTnI and cTnT are known to be very sensitive and specific for
      myocardial damage, regardless of the underlying cause. Lately, it has been found
      that cTns can be elevated and reflect worse prognoses in many situations where
      ACS is excluded. Such information can affect the validity of cTns as markers for
      ACS without classic symptoms. This may call for a revision of the troponin cutoff
      values to make a diagnosis of ACS. Furthermore, it opens a new field of study to
      determine appropriate management of patients with elevated cTn levels in whom ACS
      has been excluded.

PMID- 22477273
TI  - Morphological variations of the internal carotid artery: Prevalence,
      characteristics and association with cerebrovascular disease.
AB  - The prevalence of internal carotid artery (ICA) morphological variations (MV),
      their characteristics, and their possible association with carotid stenosis,
      vascular risk factors, and previous transient ischemic attack or ischemic stroke
      was investigated in a consecutive series of patients.Within a seven-month period,
      1217 patients (557 men and 660 women; mean age [+/- SD] 62.7+/-18.1 years)
      consecutively referred to the Laboratory of Neurosonology, University of
      L'Aquila, Italy, underwent a neck vessel examination using a high-resolution B
      mode ultrasound device with a 7.5 MHz linear phased array probe.ICA MV were
      present in 319 (26.2%) patients; they were unilateral in 201 patients (63.0%) and
      bilateral in 118 patients (37.0%). Patients with ICA MV were older than those
      without ICA MV (66.3+/-19.9 years versus 61.4+/-18.0 years, P<0.0001) and were
      mostly women (62.4%, P=0.0008). Tortuosity was present in 195 (44.6%) arteries,
      kinking in 236 arteries (54.0%) and coiling in six arteries (1.4%). Carotid
      stenosis was found in 270 patients (22.2%). Among patients with ICA stenosis, MV
      were found in 134 patients (49.6%). Mean neck length was similar in patients with
      and without ICA MV (12.1+/-2.4 cm versus 12.6+/-2.9 cm, P=0.4). In the
      multivariate logistic regression analysis, the presence of ICA MV was associated
      with female sex and older age.Tortuosity and kinking were frequently encountered
      during neurovascular examination. Their presence was usually related to aging and
      female sex, and did not imply any additive risk for stroke, although further
      studies are needed to clarify this point.

PMID- 22477274
TI  - Reversible left ventricular apical ballooning associated with jet lag in a
      Taiwanese woman: A case report.
AB  - Reversible left ventricular apical ballooning, without coronary artery stenosis,
      is a novel heart syndrome mimicking acute myocardial infarction, and is very rare
      in Taiwan. A 74-year-old Taiwanese woman returned from travelling abroad for one
      week and suffered from persistent, severe jet lag with sleep disturbance. She had
      a cold exacerbated by bronchial asthma for three days. She presented with sudden
      onset of chest pain after drinking three cups of coffee and taking a sauna for
      more than 1 h. On admission, an electrocardiogram showed ST segment elevation in
      leads II, III, aVF and V(3-6), and cardiac enzyme tests revealed minimal
      elevation. An echocardiogram showed apical ballooning and basal hyperkinesias of
      the left ventricle (LV) in systole. A coronary angiogram on the second day was
      normal, while the ST segment was still elevated, and the patient continued to
      experience chest pain. A negative T wave developed three days later. The
      electrocardiogram abnormality and LV dysfunction resolved completely six months
      later. A takotsubo (ampulla) cardiomyopathy was diagnosed. The activated
      myocardial adrenergic nervous system, stimulated by acute and marked stress in
      this patient, with more adrenergic innervations distributed in the apex of the
      LV, may be the trigger for this novel cardiac syndrome.

PMID- 22477275
TI  - Percutaneous coronary intervention in a patient with a single right coronary
      artery: A case report and review of the literature.
AB  - The present report discusses a case of successful percutaneous coronary
      intervention to abnormally originating circumflex and diagonal arteries arising
      from the right sinus of Valsalva in a patient with a single right coronary
      artery. The incidence of this rare abnormality, frequency of atherosclerosis and
      interventional procedures in this group of patients are discussed, and a review
      the literature is presented.

PMID- 22477276
TI  - Noncompaction of the ventricular myocardium in a patient with Behcet's disease
      showing multiple thrombus formations in the right atrium, inferior vena cava and
      right iliac vein: A case report.
AB  - A case of noncompaction of the ventricular myocardium in a 24-year-old man with
      Behcet's disease is reported. Transthoracic echocardiographic examination
      revealed two cardiac masses in the right atrium, pericardial fluid behind the
      right atrium and multiple muscular trabeculation in the apical part of the left
      ventricle. Subsequent transesophageal echocardiography clearly showed two
      thrombus formations in the right atrium and prominent ventricular trabeculations
      with deep intertrabecular recesses perfused from the ventricular cavity, which
      are characteristic findings of ventricular noncompaction. In addition,
      abdominopelvic computed tomography showed thrombus formation in the inferior vena
      cava and right iliac vein. These multiple thrombus formations were treated
      successfully with steroid, immunosuppressive and anticoagulant therapies. This is
      the first reported case of left ventricular noncompaction in association with
      Behcet's disease showing pericarditis and multiple thrombus formations in the
      right atrium, inferior vena cava and right iliac vein.

PMID- 22477277
TI  - Successful endovascular management of an aortic rupture following stent placement
      for severe atherosclerotic stenosis: A case report.
AB  - Aortic rupture during endovascular procedures is a devastating complication that
      mandates expedient intervention. The present report describes a case in which
      endovascular treatment was used to successfully manage an aortic rupture
      following placement of a covered stent graft for severe infrarenal aortic
      stenosis. Successful management of this case was the result of the procedure
      being performed in an operating room under appropriate anesthesia and close
      hemodynamic monitoring. Bilateral common femoral arterial access and use of
      covered aortic stent grafts also contributed to a favourable outcome.

PMID- 22477278
TI  - Developmental trajectories of chinese children's relational and physical
      aggression: associations with social-psychological adjustment problems.
AB  - The purpose of this short-term longitudinal study was to examine Chinese
      children's trajectories of physical and relational aggression and their
      association with social-psychological adjustment problems (i.e., depressive
      symptoms and delinquency) and gender. Fourth and fifth grade children in Taiwan
      (n = 739, age 9-11) were followed across 1 year. Results of Linear Mixed Models
      demonstrated that, on average, relational aggression increased in a linear
      fashion for fifth grade children and girls and physical aggression remained
      stable for boys and increased linearly for fifth grade girls. Further, increases
      in relational aggression were associated with time-dependent increases in
      depressive symptoms, and the effect size of this association seemed to be
      stronger than that of physical aggression. Findings are discussed in the context
      of Chinese culture.

PMID- 22477280
TI  - [Disorders of smell and taste].

PMID- 22477281
TI  - Editorial.

PMID- 22477279
TI  - Herbal hepatotoxicity: a hidden epidemic.
AB  - Complementary and alternative therapies, including herbal products, have become
      increasingly popular in the general population and among patients and physicians.
      Regulations and pharmacovigilance regarding herbal drugs are still incomplete and
      need to be improved. In fact, herbals are commonly marketed on the Internet, and
      in many countries they are sold as food supplements, which are beyond the control
      of drug regulatory agencies. In Europe and the U.S., reports of hepatotoxicity
      from these products, including those advertised for liver diseases, are
      accumulating. Many herbal drugs are also commonly used in children, and in women
      during pregnancy and lactation, because they are believed to be "natural" and,
      therefore, "harmless." One emerging problem is people preferring herbal-based
      slimming aids to conventional dietary and physical activity. In Italy, the use of
      non-conventional therapies has been reported for 13.6 % of the population, and
      3.7 % freely use herbal drugs, unaware of the risks associated with a potential
      interaction with prescription drugs. In our review, we discuss the problem of the
      lack of standardization of herbal drugs, the lack of randomized clinical trials
      regarding the majority of these products, the unawareness of risks by the
      patients who buy and use them, and, further, the problem of underreporting. For
      the most commonly used herbal products and slimming aids, we describe their
      potential hepatotoxicity mechanisms, the causality assessment necessary for a
      correct diagnosis, and the clinical patterns for which these products seem to be
      responsible.

PMID- 22477282
TI  - The search for the etiology of autism.
AB  - This special section on autism etiology began with the paper submitted to The
      Analysis of Verbal Behavior by Drash and Tutor, who propose that autism is a
      contingency-shaped disorder of verbal behavior. The five papers that follow the
      Drash and Tutor paper provide reactions to their analysis by several behavior
      analysts working in the autism field. Only one of the five (Malott) is fully
      supportive of Drash and Tudor's analysis of autism as a completely contingency
      shaped disorder. The other four authors recognize the importance of environmental
      variables in the development and maintenance of autistic behavior, but caution
      against the neglect of genetic and other variables such as environmental
      intrusion, and insist that a complete behavioral theory of the etiology of autism
      must involve all three variables. The series ends with Drash and Tutor's response
      to the five papers.

PMID- 22477284
TI  - A comment on Drash and Tudor's (2004) operant theory of autism.
AB  - The authors comment on Drash and Tudor's operant theory of autism. Concerns with
      the theory's face validity and empirical support are presented, along with
      concerns about four aspects of the theory.

PMID- 22477283
TI  - An analysis of autism as a contingency-shaped disorder of verbal behavior.
AB  - This paper analyzes autism as a contingency-shaped disorder of verbal behavior.
      Contingencies of reinforcement in effect during the first to third year of a
      child's life may operate to establish and maintain those behaviors that later
      result in a diagnosis of autism. While neurobiological variables may, in some
      cases, predispose some children to be more or less responsive to environmental
      variables than others, our analysis suggests that reliance on neurobiological
      variables as causal factors in autism is unnecessary. We present six paradigms
      that may play critical etiologic roles in the development of behaviors labeled as
      autistic. Recognizing these contingencies and their resulting behaviors during
      the first two years of a child's life may contribute substantially to earlier
      identification, more effective treatment and, quite possibly, to the development
      of Applied Behavior Analysis programs for the prevention of autism that could be
      implemented immediately. Conceptualizing autism as a contingency-shaped disorder
      of verbal behavior may provide a new and potentially more effective paradigm for
      behavioral research and treatment in autism.

PMID- 22477285
TI  - Autistic behavior, behavior analysis, and the gene.
AB  - This article addresses the meaning of autism, the etiology of autistic behavior
      and values, the nature-nurture debate, contingencies vs. genes, and resistance to
      a behavioral analysis of autism.

PMID- 22477286
TI  - Towards a balanced account of autism etiology.
AB  - Drash and Tudor describe six sets of reinforcement contingencies which may be
      present in the environments of some children eventually diagnosed with autism and
      suggest that these contingencies account for the etiology of "autistic"
      behaviors. Nevertheless, merely observing such contingencies in the environments
      of these children is insufficient to establish a positive correlation between the
      contingencies and "autistic" behaviors, let alone a causal relationship. To
      demonstrate a positive correlation, it is necessary to present evidence that the
      relevant contingencies are present more often in the environments of children
      exhibiting these behaviors than in the environments of children not exhibiting
      these behaviors. This condition has not been met, since no evidence to the effect
      that such contingencies are absent in the environments of typical children or
      children with disabilities other than autism has been presented. In fact, the
      opposite appears to be true, as is argued in the present commentary. It appears
      that Drash and Tudor's account of autism etiology is incomplete in that it
      neglects the role of unlearned differences between children and their possible
      interactions with the social environment in shaping "autistic" behaviors. Despite
      the misconception held by some that behavior analysis is a radically
      environmental approach, unlearned differences may be discussed within a
      behavioral framework. A "completely behavioral" account may discuss such
      differences in terms of susceptibility to reinforcement or punishment, speed of
      conditioning, or other unlearned characteristics which are potentially testable.

PMID- 22477287
TI  - Commentary on Drash and Tudor: An analysis of autism as a contingency-shaped
      disorder of verbal behavior.
AB  - A critique is presented of the etiological model for autism as presented by Drash
      and Tudor. The model is rejected based upon conceptual and methodological
      grounds. The major points raised concern overgeneralization of research findings,
      limitations of single subject methodology to answer population based questions,
      current neurobiological research, and the danger of uni-dimensional models.
      Specific examples of cases that do not fit Drash and Tudor model are presented.

PMID- 22477288
TI  - Autism as a contingency-shaped disorder of verbal behavior: Evidence obtained and
      evidence needed.
AB  - Drash and Tudor's argument that autism is a contingency-shaped disorder of verbal
      behavior is logical and consistent with behavioral principles, but the argument's
      premises have no direct empirical support and some conflicting evidence. The
      quantity and quality of research needed to support such a theory is compared to
      that found in the area of antisocial behavior in children, which has considerable
      evidence for a contingency-shaped etiology. Even if autism is largely inherited,
      this does not weaken the necessity or importance of behavioral intervention.
      Drash and Tudor's paper may serve a useful function by outlining areas in need of
      further study because a great deal more research is needed on how the early
      environment shapes the language, cognitive, and behavioral development of
      children.

PMID- 22477289
TI  - Is autism a preventable disorder of verbal behavior? A response to five
      commentaries.
AB  - This paper presents a response to five commentaries on our article An Analysis of
      Autism as a Contingency-Shaped Disorder of Verbal Behavior (Drash & Tudor, 2004).
      One of the principal objectives of that article is to provide the behavior
      analysis community and the autism community with a conceptual basis for analyzing
      autism as a behavioral disorder rather than a neurological disorder. This
      analysis provides a logical and testable behavioral answer to the question of the
      etiology of autism, a question that has baffled scientists and researchers for
      more than half a century. Elements of the original article with which reviewers
      expressed concern include: need for more data, need for greater emphasis on
      neurological and epidemiological factors in autism, the relative importance of
      verbal behavior as a core deficit of autism, and disruptive and avoidant behavior
      as a primary variable in the etiology of autism. We provide a behavioral response
      to each of these concerns. We also show how our analysis will provide a
      conceptual foundation for behavior analysis to begin developing urgently needed
      programs for prevention and earlier intervention in autism.

PMID- 22477291
TI  - Meaning: A verbal behavior account.
AB  - Although the verbal operants that comprise Skinner's account of verbal behavior
      provide a seemingly complete description of the behavior of the speaker with
      respect to what is ordinarily called the expression of meanings, it may be shown
      that the account is intrinsically deficient in describing the receptive behavior
      of listeners with regard to their comprehension of the meanings of novel words,
      sentences and propositions. In response to this perceived deficiency, the notion
      of joint control is presented here. Joint control occurs when a verbal-operant
      topography, currently evoked by one stimulus, is additionally (i.e., jointly)
      evoked by a second stimulus. This event of joint stimulus control then sets the
      occasion for a response. This simple mechanism is shown here to have exceedingly
      broad explanatory properties: providing a coherent and rigorously behavioral
      account of various aspects of language ranging from meaning, reference and
      comprehension, to the development of abstraction in children's speech.

PMID- 22477290
TI  - Emergence of untaught mands or tacts of novel adjective-object pairs as a
      function of instructional history.
AB  - We tested the effects of multiple exemplar instruction (MEI) on the emergence of
      untaught mands or tacts of adjective-object pairs in a multiple-probe design
      across four students with autism/developmental disabilities. None of the students
      emitted either mands or tacts for three sets of three adjective-object pairs
      (word sets counterbalanced across students and conditions) in pre-experimental
      probe trials. In the baseline phase, either mands or tacts were taught for the
      first adjective-object pairs to each student who then received probe trials for
      the untaught verbal operants. None of the students emitted the verbal operant
      that was not directly taught. In the MEI condition, a second set of adjective
      object pairs was taught under alternating mand and tact conditions until both
      operants were mastered. Following mastery of the second set in the MEI condition,
      students were again probed for the untaught mands or tacts for the adjective
      object pairs that were not in their repertoires when a single verbal operant was
      taught in baseline (the first set). All students emitted the untaught mands or
      tacts for the first set. Finally, a third set of adjective-object pairs was
      taught as tacts or mands and the untaught mands or tacts emerged. The data are
      discussed in terms of generative verbal behavior, abstraction of establishing
      operation control, and multiple exemplar instruction.

PMID- 22477292
TI  - Engineering discovery learning: The contingency adduction of some precursors of
      textual responding in a beginning program.
AB  - A learning situation in which the principal content of what is to be learned is
      not given but is independently discovered by the learner is often considered
      "discovery learning." Recently, learning scientists have been able to make
      explicit some of the conditions under which such independent discovery is likely
      to occur (Andronis, 1983; Epstein, 1996; Johnson & Layng, 1992). One form of
      "discovery" can often be observed when skills learned under one set of conditions
      are recruited under new conditions to serve a new or different function-a process
      of "contingency adduction" (Andronis, Layng, & Goldiamond, 1997). The research
      reported here investigated the application of contingency adduction in a
      discovery learning context to establish sound-to-letter correspondence as part of
      an online reading/decoding program, Headsprout Early Reading. Beginning readers
      acquired novel letters/sounds correspondence with minimal presentations and few
      errors-often requiring only one presentation. This research suggests that
      instructional sequences may be designed to provide effective discovery learning
      activities to teach some phonics skills.

PMID- 22477293
TI  - Dialogue on private events.
AB  - In the fall of 2003, the authors corresponded on the topic of private events on
      the listserv of the Verbal Behavior Special Interest Group. Extracts from that
      correspondence raised questions about the role of response amplitude in
      determining units of analysis, whether private events can be investigated
      directly, and whether covert behavior differs from other behavior except in
      amplitude. Most participants took a cautious stance, noting not only conceptual
      pitfalls and empirical difficulties in the study of private events, but doubting
      the value of interpretive exercises about them. Others argued that despite such
      obstacles, in domains where experimental analyses cannot be done, interpretation
      of private events in the light of laboratory principles is the best that science
      can offer. One participant suggested that the notion that private events can be
      behavioral in nature be abandoned entirely; as an alternative, the phenomena
      should be reinterpreted only as physiological events.

PMID- 22477294
TI  - Notation systems for reading and writing sign language.
AB  - Without written forms, signed languages do not permit the type of textual record
      available to speakers of English and other written languages. Deaf signers have
      generally relied on the language of the dominant hearing culture for this
      purpose. Because of their visual-gestural modality, signed languages present a
      unique set of challenges for developing written forms. These issues are
      considered from a behavioral perspective, and two sign language notation systems,
      Stokoe Notation and Sutton SignWriting, are described.

PMID- 22477295
TI  - Advanced behavioral applications in schools: A review of R. Douglas Greer's
      designing teaching strategies: An applied behavior analysis systems approach.
AB  - R. Douglas Greer(1)s Designing Teaching Strategies is an important book directed
      to advanced students in applied behavior analysis for classrooms. This review
      presents some of the striking features of the Comprehensive Applied Behavior
      Analysis to Schooling (CABAS(r)) program and the individualized instruction that
      the book advances. These include its instruction in literacy, its use of
      graphing, and its flexibility in systematic organization. Although its
      readability could be improved, this book has much to recommend it in an approach
      that has acquired an international following.

PMID- 22477296
TI  - A behavioral look at the training of Alex: A review of Pepperberg's the Alex
      studies: Cognitive and communicative abilities of grey parrots.
AB  - The Alex Studies: Cognitive and Communicative Abilities of Grey Parrots by Irene
      Pepperberg is reviewed from a behavior analytic orientation. The results of the
      majority of her experiments are discussed in terms drawn from the general
      literature of behavior analysis and Skinner's analysis of verbal behavior. We
      conclude that she has provided evidence of the complex control of vocal behavior
      that illustrates a functional verbal repertoire of tacts and mands. This book
      suggests several areas for future research on the methods needed to establish
      verbal repertoires in species other than humans.

PMID- 22477298
TI  - Inflammation and platelet activation in peripheral arterial occlusive disease.
AB  - OBJECTIVES: Epidemiological evidence indicates that inflammation accompanies the
      progression of atherosclerosis. The aim of the present cross-sectional study was
      to define relationships between platelet activation and inflammation in patients
      with mild to severe (stages II to IV) peripheral arterial occlusive disease
      (PAOD) and matched controls. The effect of chronic administration of low-dose
      acetylsalicylic acid was investigated. METHODS: Subjects were studied on a single
      occasion. C-reactive protein (CRP) and two indexes of in vivo platelet activation
      were measured - the urinary excretion of 11-dehydrothromboxane (TX) B(2) by
      immunoassay and circulating platelet-monocyte aggregates (PMAs) by flow
      cytometry. RESULTS: Plasma PMAs and urinary 11-dehydro-TXB(2) were significantly
      increased in PAOD patients compared with controls (P<0.01 for all). A positive
      correlation between 11-dehydro-TXB(2) and CRP was found in the study population
      (r(s)=0.63, P<0.001). Using logistic regression analysis, CRP was the only
      independent correlate of 11-dehydro-TXB(2) (beta(CRP)=11.9, P<0.01), whereas only
      the presence of PAOD was an independent predictor of high PMA levels
      (beta(PAOD)=13.7, P=0.001). Chronic administration of acetylsalicylic acid
      reduced 11-dehydro-TXB(2), but not PMA and CRP. CONCLUSIONS: There is evidence
      that platelet activation in patients with PAOD is related to the vascular disease
      and is dependent on the severity of inflammation.

PMID- 22477297
TI  - Cigarette smoke and adverse health effects: An overview of research trends and
      future needs.
AB  - A large volume of data has accumulated on the issues of tobacco and health
      worldwide. The relationship between tobacco use and health stems initially from
      clinical observations about lung cancer, the first disease definitively linked to
      tobacco use. Almost 35 years ago, the Office of the Surgeon General of the United
      States Health Service reviewed over 7000 research papers on the topic of smoking
      and health, and publicly recognized the role of smoking in various diseases,
      including lung cancer. Since then, numerous studies have been published that
      substantiate the strong association of tobacco use with a variety of adverse
      human health effects, most prominently with cancer and cardiovascular diseases.
      Cigarette smoking is regarded as a major risk factor in the development of lung
      cancer, which is the main cause of cancer deaths in men and women in the United
      States and the world. Major advances have been made by applying modern genetic
      technologies to examine the relationship between exposure to tobacco smoke and
      the development of diseases in human populations. The present review summarizes
      the major research areas of the past decade, important advances, future research
      needs and federal funding trends.

PMID- 22477299
TI  - Dose-dependency in pleiotropic effects of atorvastatin.
AB  - Statins are recognized as the principal and most effective class of drugs for
      reducing serum cholesterol levels and, therefore, significantly reducing
      cardiovascular events and mortality. Statins may have a wide range of beneficial
      biological effects in addition to lipid lowering, a phenomenon commonly termed a
      'pleiotropic effect'. However, the dose-dependency of these effects remains
      unclear. The present study evaluated whether atorvastatin, a potent statin,
      ameliorates the serum markers of pleiotropic effects, with a focus on dose
      dependency. The pleiotropic effects of treatment with atorvastatin 5 mg/day and
      10 mg/day for six months each in 15 patients with primary hypercholesterolemia
      were assessed in a prospective, randomized, open-label, crossover, single-centre
      study. Atorvastatin treatment dose-dependently decreased a serum marker of
      oxidative stress as well as the serum low-density lipoprotein cholesterol level.
      However, serum markers of inflammation and fibrinolysis decreased independently
      of dose. In conclusion, the dose-dependency of atorvastatin's pleiotropic effects
      differs among individual biological effects.

PMID- 22477300
TI  - Interaction between the heme oxygenase system and aldosterone in hypertension.
AB  - The chronic intraperitoneal administration of the heme oxygenase inducer, hemin
      (15 mg/kg daily), for three weeks reduced blood pressure in adult spontaneously
      hypertensive rats (SHR) from 210.1+/-1.03 mmHg to 127+/-0.9 mmHg (n=10, P<0.01)
      but had no effect on age-matched normotensive Wistar-Kyoto or Sprague-Dawley
      strains. The antihypertensive effect of hemin was accompanied by reduced
      expression of aldosterone synthase messenger RNA and depleted levels of plasma
      aldosterone (675.7+/-121.6 pg/mL versus 365.7+/-37 pg/mL; n=4, P<0.05).Because
      aldosterone is known to stimulate phospholipase C (PLC), the effect of hemin on
      PLC was examined. Hemin abated PLC activity (29.6+/-1.5 nmol/min/mL versus 3.1+/
      0.9 nmol/min/mL; n=5, P<0.01) and this was accompanied by depleted levels of
      intracellular calcium (551+/-46 nM versus 103.2+/-6.3 nM; n=4, P<0.01) in the
      aorta of SHR. In contrast, enhanced heme oxygenase activity and elevated cyclic
      GMP levels (17.74+/-0.08 pmol/mg versus 30.4+/-2.3 pmol/mg protein; n=6, P<0.01)
      were detected in hemin-treated SHR. Additionally, hemin therapy also suppressed
      inflammatory and oxidative insults by significantly reducing nuclear factor kappa
      B messenger RNA expression while enhancing the total antioxidant capacity (0.22+/
      0.02 Trolox equivalent antioxidant capacity (TEA C)/mg protein versus 0.60+/-0.04
      TEA C/mg protein; n=4, P<0.01).The concomitant depletion of aldosterone, PLC
      activity, intracellular calcium and the corresponding decline of inflammatory and
      oxidative insults may account for the antihypertensive effects of hemin.

PMID- 22477301
TI  - The coral reef aorta - a single centre experience in 70 patients.
AB  - Coral reef aorta (CRA) is described as rock-hard calcifications in the visceral
      part of the aorta. These heavily calcified plaques grow into the lumen and can
      cause significant stenoses, which may lead to malperfusion of the lower limbs,
      visceral ischemia or hypertension due to renal ischemia. From January 1984 to
      February 2007, 70 patients (24 men, 46 women, mean age 59.5 years, range 14 to 81
      years) underwent treatment in the Department of Vascular Surgery and Renal
      Transplantation, University Hospital, Heinrich-Heine-University (Dusseldorf,
      Germany) for CRA. The present study is based on a review of patients' records and
      the prospective follow-up in the outpatient clinic. The most frequent finding was
      renovascular arterial hypertension (44.3%) causing headache, vertigo and visual
      symptoms. Intermittent claudication due to peripheral arterial occlusive disease
      was found in 28 patients (40.0%). Seventeen patients (24.3%) presented with
      chronic visceral ischemia causing diarrhea, weight loss and abdominal pain. Sixty
      nine of the 70 patients (98.6%) underwent surgery; in 57 patients, aortic
      reconstruction was achieved with thromboendarterectomy, performed on an isolated
      suprarenal segment in six cases (8.7%), an infrarenal segment in 15 cases
      (21.7%), and the supra- and infrarenal aorta in 43 cases (62.3%). Eight patients
      (11.6%) died during or soon after surgery. Postoperative complications requiring
      corrective surgery occurred in 11 patients (15.9%). Almost one-third of the
      patients (n=19, 27.5%) returned for follow-up after a mean of 52.6 months (range
      six to 215 months). Of the 19 patients, there was significant clinical and
      diagnostic improvement in 16 patients (84.2%) and three patients (15.8%) were
      unchanged. Impairment was not observed. Despite the existing and improving
      surgical techniques for the treatment of CRA, its pathophysiological basis and
      genesis is not yet understood.

PMID- 22477302
TI  - Multiple basilic vein aneurysms concomitant with multiple hemangiomas of the
      upper extremity: A case report.
AB  - Basilic vein aneurysms are rare clinical entities. A 21-year-old woman with
      basilic vein aneurysms and multiple hemangiomas in the right upper extremity is
      presented. The case is discussed in light of the relevant literature with
      emphasis on the use of Doppler ultrasonography and magnetic resonance venography.

PMID- 22477303
TI  - Recurrent spontaneous coronary artery dissection: A case report and review of the
      literature.
AB  - Spontaneous coronary artery dissection is a rare cause of acute coronary
      syndrome. Recurrent spontaneous dissection is even more rare. A case of recurrent
      coronary artery dissection is reported and the literature is reviewed.

PMID- 22477304
TI  - Sarcoidosis, microvascular angina and aortitis: New dimensions of the 'Takayasu
      syndrome' - A case report.
AB  - A case of Takayasu aortitis associated with sarcoidosis presenting with recurrent
      angina is reported. This association has been called 'Takayasu syndrome', which
      reflects what is likely a shared etiology. Myocardial perfusion abnormalities
      have recently been documented in sarcoidosis, but this case clarifies for the
      first time that the angina in Takayasu syndrome is likely due to small vessel
      coronary arteritis. Corticosteroids and cytotoxic therapy have been shown to be
      beneficial in all forms of sarcoidosis related to vasculitis. Initiation of
      steroid therapy may provide relief of angina in patients with evidence of
      reversible ischemia in normal coronary arteries.

PMID- 22477305
TI  - Myocardial bridging: A 'forgotten' cause of acute coronary syndrome - a case
      report.
AB  - During a stress test, an asymptomatic 40-year-old man showed an ST depression
      above 4 mm and a horizontal ST depression above 2 mm in the V3 to V6 precordial
      leads during the recovery phase, without symptoms related to myocardial ischemia.
      After several days, he experienced recurrent episodes of oppressive retrosternal
      pain with radiation to the interscapular region, associated with stress dyspnea.
      Stress myocardial scintigraphy using technetium sestamibi was performed, which
      showed a modest push-pull deficit of perfusion in the septal-anterior basal area
      associated with a small deficit of perfusion in the apical region.The patient was
      admitted to hospital with a diagnosis of unstable angina. Repeated episodes of
      chest pain appeared during this period, which were partially relieved with the
      administration of sublingual nitrate. There were no significant changes in the
      electrocardiogram or cardiac enzyme levels. Coronary angiography showed initial
      parietal hypertrophy with normal segmentary kinesis and global systolic function
      and, most importantly, the presence of a systolic narrowing (myocardial bridging)
      of the middle one-third of the left anterior descending artery from the likely
      intramyocardial route. There was no significant stenosis of the remaining
      coronary tracts.Myocardial bridges have traditionally been considered a benign
      condition, but recent studies have demonstrated that the clinical complications
      can be dangerous; these complications include acute coronary syndromes,
      arrhythmias (including supraventricular tachycardia and ventricular tachycardia),
      exercise-induced atrioventricular conduction blocks, transient ventricular
      dysfunction and sudden death.

PMID- 22477307
TI  - Editorial.

PMID- 22477306
TI  - Delayed pseudoaneurysm repair: A case report.
AB  - Iatrogenic pseudoaneurysms are a complication of arterial catheterization
      performed for both diagnosis and intervention. Their incidence is approximately
      1% following diagnostic catheterizations and 3.2% after interventional
      procedures. The symptoms of iatrogenic pseudoaneurysm are pain and swelling. The
      preferred method of treatment consists of thrombin injection under ultrasound
      guidance, although compression can be used. Most published research describes
      pseudoaneurysms that occurred close to the time of catheterization; the present
      case report describes a patient who presented two years postcatheterization with
      a symptomatic pseudoaneurysm.

PMID- 22477308
TI  - E. L. Moerk: remembrances.

PMID- 22477309
TI  - Remembrance of ernst L. Moerk.

PMID- 22477310
TI  - Ernst moerk and the puzzle of zero-trial learning.

PMID- 22477311
TI  - Expanding Vocal Requesting Repertoires via Relational Responding in Adults with
      Severe Developmental Disabilities.
AB  - The purpose of this project was to demonstrate untrained vocal requests in three
      adults with severe developmental disabilities. Specifically, we evaluated whether
      a history of reinforced relational responding would give rise to untrained vocal
      requests for novel items. Participants were first taught to request preferred
      items using their category names. They were then taught conditional
      discriminations between pictures of preferred items that were categorically
      related. Finally, participants were tested for their abilities to request items
      that had not been originally presented during request training, using their
      category names. All participants demonstrated untrained requests, and for some
      participants, changes in the mand repertoire were accompanied by changes in the
      tact repertoire. Some participants also showed generalization of skills across
      settings.

PMID- 22477312
TI  - The effects of multiple-tact and receptive-discrimination training on the
      acquisition of intraverbal behavior.
AB  - The purpose of this study was to determine whether multiple-tact training and
      receptive-discrimination training could be used to teach thematically related
      vocal intraverbals to typically developing preschool children. Multiple-tact
      training involved teaching a child to name both the item and the category to
      which the item belonged. Receptive-discrimination training consisted of teaching
      a child to select a picture card in the presence of a question from the
      experimenter regarding the item or its category. When neither of these strategies
      resulted in substantial increases in intraverbal responses, a typical intraverbal
      training protocol using tact prompts was implemented. Six typically developing
      children participated in the study. A multiple-baseline design across word
      categories was used to evaluate the effects of the three training procedures.
      Results indicated that both multiple-tact and receptive-discrimination training
      had minimal effects on the strength of the intraverbal repertoire, whereas direct
      intraverbal training had a more substantial effect. The results provide some
      evidence of the functional independence of verbal operants, as well as the
      independence of listener and speaker repertoires. Receptive-discrimination and
      multiple-tact training may have facilitated acquisition of intraverbals; however,
      further research is needed to assess how these repertoires might interact with
      each other.

PMID- 22477313
TI  - Evaluating stimulus-stimulus pairing and direct reinforcement in the
      establishment of an echoic repertoire of children diagnosed with autism.
AB  - Many children with autism do not imitate adult vocalizations, an important skill
      in learning to talk. Pairing adult vocalizations with preferred stimuli has been
      shown to increase free-operant vocalizations but effects are temporary; thus,
      direct reinforcement may be necessary to establish durable vocal behaviors. In
      Experiment 1, directly reinforced echoic responses did not increase following
      stimulus-stimulus pairings in three children with autism. Similarly, pairings did
      not increase free-operant vocalizations in Experiment 2, a replication of Miguel
      et al. (2002). Experiment 3 demonstrated that shaping increased vowel frequency
      for one participant. Results suggest that variables are yet to be delineated that
      influence effectiveness of a stimulus-stimulus pairing procedure on vocalization
      frequency and acquisition of a verbal operant following such pairings.

PMID- 22477314
TI  - Emergence of Mands and Tacts of Novel Objects among Preschool Children.
AB  - According to Skinner's (1957) analysis of verbal behavior, the mand and the tact
      are functionally independent verbal operants, each of which is acquired through a
      unique history of reinforcement. The present study attempted to replicate the
      findings of Lamarre and Holland (1985), who empirically demonstrated functional
      independence of mands and tacts in typically developing preschool children. Five
      children participated. All were initially trained to complete two 4-piece
      assembly tasks. Four children were then trained to tact the four pieces that
      comprised one of the assembly tasks, and to mand for the four pieces that
      comprised the other task, using arbitrary vocal response forms. The remaining
      child received tact training only, and only on one task. The effects of training
      on the untrained operant were evaluated in a multiple-probe design across tasks.
      Following mand training, 4 out of 4 children reliably emitted tacts under testing
      conditions, while the effects of tact training differed across participants. The
      results differ from those of Lamarre and Holland, but are not necessarily
      surprising from the point of view of either Skinner's analysis or more recent
      behavioral accounts of language. Future research should attempt to identify
      variables that affect transfer between mand and tact relations.

PMID- 22477315
TI  - An Analog Study of First Language Dominance and Interference over Second
      Language.
AB  - The purpose of this study was to design a model for "first language" dominance
      over "second language" performance and the interference of one language over the
      other. Two sets of equivalence relations showing a common element (i.e., the
      reference) were established under different contextual conditions. One set
      ("first language") was over trained relative to the other ("second language").
      Dominance of the "first language," as demonstrated in relations involving the
      common element, was determined by examining performances in the absence of
      contextual stimuli. Interference by one language over the other was modeled by
      examining the degree to which resurgence of "first language" and "second
      language" relations would occur in extinction, following a period of exposure to
      inconsistent test trials. In addition, both selection-based (i.e., copy text) and
      topography-based (i.e., intraverbal) equivalence were examined in these areas.
      The results demonstrated that the development of an analog for a bilingual
      repertoire, the domination of the "first language" over the "second language" and
      the interference of one language over the other, were established.

PMID- 22477316
TI  - Novel dictation and intraverbal responses as a function of a multiple exemplar
      instructional history.
AB  - We tested the effect of multiple exemplar instruction (MEI) on acquisition of
      joint spelling responses, vocal to written and vice versa, for three sets of five
      words by four kindergarteners with language delays using a delayed multiple probe
      design. First, students were taught to spell Set 1 as either vocal or written
      responses (two vocal and two written) and probed on untaught responses. Next
      students were taught Set 2 using MEI (i.e., alternating responses) and again
      probed untaught responses for Set 1. Finally, Set 3 was taught in a single
      response and students were probed on untaught responses. Two students spelled
      none of Set 1 untaught responses before MEI, while two spelled the words at 60%
      accuracy or 10% accuracy. After MEI on Set 2, all students spelled untaught
      responses for Set 1 at 80% to 100% accuracy and Set 3 at 80% to 100% accuracy.
      The MEI resulted in joint stimulus function such that formerly independent
      responses came under the same stimulus control. We replicated these results with
      four other kindergartners with autism who performed academically above their
      typically developing peers. The results are discussed in terms of Skinner's
      treatment of the independence of the two verbal operants.

PMID- 22477317
TI  - Self-management of Initiations by Students Diagnosed with Autism.
AB  - During prebaseline observations, three students diagnosed with autism were unable
      to make social initiations to another individual. The ability to make initiations
      would be considered a "pivotal response" in that it would allow an individual to
      come into contact with a wide variety of social reinforcement. A multiple
      baseline design was implemented to measure the effects of a using a self
      management package to teach the students to make social initiations. Two
      interventionists worked with each student to prompt and reinforce initiations.
      All students acquired social initiations during externally-determined
      reinforcement. The initiations were maintained when reinforcement changed from
      externally determined to a self-management system. The prompts to initiate and
      self-reinforce were faded over the course of the sessions. The use of self
      management by the student led to less need for staff intervention. Implications
      from the literature are discussed.

PMID- 22477318
TI  - The emergence of the listener to speaker component of naming in children as a
      function of multiple exemplar instruction.
AB  - We tested the effect of multiple exemplar instruction on the transfer of stimulus
      function for unfamiliar pictures across listener responses (i.e., matching and
      pointing) and speaker responses (i.e., pure tacts and impure tacts). Three
      preschool students, who were 3- and 4-year-old males and did not have the
      listener to speaker component of the naming repertoire, participated in the
      experiment. The dependent variable was numbers of correct responses to probe
      trials of both untaught listener responses ("point to__") and speaker responses
      (tact and impure tacts) following mastery of matching responses for two sets of
      five unfamiliar pictures (Set 1 and Set 3). After each participant mastered
      matching (e.g., "match Labrador") for Set 1 pictures they were probed on the
      three untaught responses to Set 1 words. That is, they were asked to point to
      Labrador, tact the picture of Labrador, and respond to the picture of a Labrador
      and the question "What is this?" Next, the participants were taught mastery of
      all four types of responses using MEI for a second set of five pictures (Set 2)
      and probed again on the 3 untaught Set 1 responses. Finally, matching responses
      were taught to mastery for a novel set of pictures (Set 3) and then probed on the
      three untaught responses. The results showed that untaught speaker responses
      emerged at 60% to 85% for two participants, and 40%-70% for one participant. We
      discuss the role of instructional history in the development of the listener to
      speaker component of naming.

PMID- 22477319
TI  - The effects of deprivation, presession exposure, and preferences on teaching
      manding to children with autism.
AB  - The effects of at least 23-hr deprivation, 5-min presession exposure, and
      individual preference on the acquisition of mands were investigated in these
      studies. Two boys who were 2.5 years old and diagnosed with autism participated
      in the studies. Preference assessments were conducted to identify preference
      levels of various toys. Toys of various preferences were then assigned to either
      a 23-hr deprivation or 5-min presession exposure condition for mand training.
      Both deprivation and preference level affected acquisition of mands. Implications
      for teaching children to mand are discussed.

PMID- 22477320
TI  - Reducing palilalia by presenting tact corrections to young children with autism.
AB  - Palilalia, the delayed repetition of words or phrases, occurs frequently among
      individuals with autism and developmental disabilities. The current study used a
      combined multiple baseline and reversal design to investigate the effectiveness
      of presenting tacts as corrections for palilalia. During baseline, five
      preschoolers with autism emitted high rates of palilalia and low rates of mands
      and tacts during play and instructional activities. During treatment, when
      experimenters presented opportunities to echoically tact actions and objects
      following the emission of palilalia, its frequency decreased to low and stable
      levels and mands and tacts increased. Functional relationships between the tact
      corrections and emissions of palilalia, mands, and tacts were established during
      reversals to baseline and treatment conditions. Similar trends in responding were
      found for frequency of palilalia, mands, and tacts in non-treatment settings.

PMID- 22477321
TI  - Using transfer procedures to teach tacts to a child with autism.
AB  - This applied study attempted to evaluate a combination of transfer procedures
      commonly used to teach tacts to children with autism. A receptive to echoic to
      tact transfer and an echoic to tact transfer procedure were combined during 5-min
      instructional sessions to teach tacts to a seven-year-old vocal child with
      autism. A multiple baseline design across three sets of ten tacts was used.
      Without the teaching procedure, the child acquired no target tacts. With the 5
      min teaching procedure implemented first with Set 1 then with Sets 2 and 3,
      respectively, the child acquired thirty new tacts over sixty teaching sessions.
      The results have wide application for children with and without autism who need
      instruction to learn tacts.

PMID- 22477322
TI  - Meaning and Verbal Behavior in Skinner's Work from 1934 to 1957.
AB  - This paper explores the historical development of Skinner's treatment of meaning
      from 1930 to 1957. Twelve papers published between 1934 and 1957, and parts of
      The Behavior of Organisms and Science and Human Behavior related to verbal
      behavior, were analyzed. Before 1945 meaning was taken as a property of the
      verbal response, and from 1945 on, meaning was supposed to be found among the
      determiners of a verbal response. We argue that these different conceptions of
      meaning were related to distinct aspects of Skinner's explanatory system.
      Finally, the notion of meaning presented by Skinner in 1945 is related to the
      theoretical breakthrough represented by Skinner's assertion of the three-term
      contingency. This idea permitted verbal behavior to be analyzed in terms of its
      functions.

PMID- 22477323
TI  - Autistic Behavior, Behavior Analysis, and the Gene-Part II.
AB  - This article reviews the negative behavior-analytic commentary on Drash and
      Tudor's behavior-analytic analysis of the etiology of autistic repertoires and
      values. This article also asks that, in our effort to scrub it clean, we not
      drown Drash and Tudor's beautiful, but fragile, new-born, behavior-analytic baby
      in hyper-methodological, hyper-scholarly bathwater.

PMID- 22477324
TI  - The secrets of scheherazade: toward a functional analysis of imaginative
      literature.
AB  - A functional analysis of selected aspects of imaginative literature is presented.
      Reading imaginative literature is described as a process in which the reader
      makes indirect contact with the contingencies operating on the behavior of story
      characters. A functional story grammar is proposed in which the reader's
      experience with a story is interpreted in terms of escape contingencies in which
      the author initially introduces an establishing operation consisting of a source
      of tension, which is resolved in some way by the outcome of the story. Although
      escape contingencies represent the functional basis for the structure of stories,
      they are to be understood in a context of many other reinforcers for reading
      fiction. Other contingencies that maintain reading are discussed. Functional
      analyses of imaginative literature have much to offer, both in improving literary
      education and in understanding the behavioral processes that occur on the part of
      the reader.

PMID- 22477325
TI  - A Philosopher's War on Poverty of the Stimulus Arguments: A Review of Fiona
      Cowie's What's Within? Nativism Reconsidered.
AB  - In What's Within? Nativism Reconsidered 1999 Fiona Cowie addresses three
      questions: (1) What is nativism? (2) What is meant by calling some trait
      "innate"? and (3) What types of evidence should be offered when claiming
      innateness? This review concentrates on these questions as they pertain to
      Chomsky's faculties-based account of language acquisition. In particular, this
      review focuses on Cowie's critique of three versions of the poverty of the
      stimulus argument (POSA): (1) the a posteriori POSA, (2) the logical problem
      POSA, and (3) the iterated POSA. In addition, counter arguments to her critique,
      and Cowie's response, in turn, to some of those counter arguments, are also
      reviewed.

PMID- 22477326
TI  - Management of small asymptomatic abdominal aortic aneurysms - a review.
AB  - The approach for abdominal aortic aneurysms (AAAs) larger than 55 mm is well
      defined due to the risk of rupture being higher than 10% per year, and a 30-day
      perioperative mortality rate between 2.5% and 5%. However, the approach for small
      asymptomatic AAAs is less well defined.There are different definitions given to
      describe a small AAA. The one the authors accepted and applied is "a localized,
      permanent and irreversible dilation of the aorta of at least 50% in relation to
      the normal adjacent infrarenal or suprarenal aorta, with a maximum diameter
      between 30-55 mm".The investigators of the largest study on small AAAs (United
      Kingdom Small Aneurysm Trial [UK-SAT]) concluded, in brief, that ultrasound
      monitoring is the most appropriate solution because the results do not support a
      policy of surgical restoration for AAAs with a diameter of between 40 mm and 55
      mm.The aim of the present review article is to highlight several challenges that
      could change the limits or create a more flexible deciding factor in the
      management of AAAs. There are multiple factors that influence surgical decision
      making, and the limit on aneurysm diameter that indicates surgery should depend
      on the patient's age, life expectancy, general status, associated diseases,
      diameter in relation to body mass, risk factors, sex, anxiety and compliance
      during the follow-up period. Monitoring is an acceptable alternative for AAAs
      between 40 mm and 55 mm, and is probably the best solution for high-risk
      patients. Surgery is the most reasonable solution for patients who are at
      moderate risk, have a significant life expectancy, are less than 70 to 75 years
      of age, and/or have aortic aneurysms larger than 50 mm.

PMID- 22477327
TI  - Effects of age, sex and smoking on ankle-brachial index in a Finnish population
      at risk for cardiovascular disease.
AB  - BACKGROUND: Smoking is a well-known risk factor for peripheral arterial disease
      (PAD). Data regarding differences in the prevalence of PAD between sexes are
      somewhat controversial. In addition, most studies indicate that the prevalence of
      PAD increases with age in both sexes. In the present study, the effects of sex,
      age and smoking on the ankle-brachial index (ABI) in a Finnish cardiovascular
      risk population were investigated. OBJECTIVES: To investigate the relationship
      between the ankle-brachial index, and age, sex and smoking in a Finnish
      population at risk for cardiovascular disease. METHODS: All men and women between
      45 and 70 years of age living in a rural town (Harjavalta, Finland; total
      population 7700) were invited to participate in a population survey (Harmonica
      study). Patients with previously diagnosed diabetes or vascular disease were
      excluded. In total, 2856 patients were invited to participate in the study. From
      these subjects, a cardiovascular risk population was screened. Complete data were
      available from 1028 persons. ABI (the ratio between the posterior tibial or
      dorsalis pedis artery and brachial artery pressures) was measured, and
      questionnaires were used to detect smoking status and relevant medical history.
      Only current smoking status was taken into account. RESULTS: The mean ABI for the
      entire study population was 1.10 (range 0.56 to 1.64). Current smokers had a
      lower mean ABI (1.06; P<0.001). There was no statistically significant difference
      in ABI values among age groups, although the majority of patients with ABI values
      below 0.9 were older than 60 years of age. There was no statistically significant
      difference in ABI between sexes. CONCLUSION: As previously reported, the present
      study shows the significant effect of smoking in the development of PAD. No
      statistically significant difference was found among age groups, but the tendency
      was toward lower ABIs in the oldest age groups. Sex had a minimal effect on the
      ABI.

PMID- 22477328
TI  - Outcome of blood pressure and renal function in patients with renal artery
      stenosis after stenting.
AB  - OBJECTIVE: To study the response of systolic and diastolic blood pressure (BP)
      and renal function after renal artery stenting at three months, six months, one
      year and last follow-up. METHODS: Patients with significant renal artery stenosis
      who underwent angioplasty with stenting from January 1999 to September 2006 were
      analyzed. The BP and serum creatinine levels were recorded at baseline, three
      months, six months, one year and at last follow-up. Generalized estimating
      equations were applied to analyze the changes in blood pressure and serum
      creatinine over time. RESULTS: There were 32 patients - 21 Chinese, six Malay and
      five Indian. The male to female ratio was 1.3:1. The mean age (+/- SD) was 69.4+/
      8.8 years. The mean follow-up time was 1.8+/-1.6 years (range 0.5 to six years).
      When compared with the baseline BP, there was significant improvement at three
      months, six months, one year and at last follow-up. In the diabetes mellitus (DM)
      group, there was deterioration in serum creatinine. In the non-DM group, there
      was stabilization of serum creatinine with improvement at one year. CONCLUSION:
      Significant improvement in BP occurs in renal artery stenosis patients after
      stenting. In patients without DM, renal function remains stable or improves.
      However, in DM patients, especially those with proteinuria, there is
      deterioration in renal function.

PMID- 22477329
TI  - Blood pressure reactions to insulin treatment in patients with type 2 diabetes.
AB  - BACKGROUND: The initiation of insulin therapy may be easy and uncomplicated in
      some patients with type 2 diabetes, but in others, mainly in obese patients,
      problems often arise (ie, poor compliance, worsening B-cell function and/or
      insulin resistance). METHODS: As a substudy of a broader investigation concerning
      hemorheological effects of insulin treatment in insufficiently controlled type 2
      diabetes, blood pressure was recorded in 12 patients at baseline, after two
      months and after four months on insulin. RESULTS: After two months on insulin,
      analyses of triglycerides, high-density lipoprotein cholesterol and total
      cholesterol indicated metabolic improvement (P<0.05 to 0.001) and a surprisingly
      uniform increase of blood pressure values (P<0.05 to 0.01) was found. At the same
      time, the serum sodium concentration increased (P<0.01) and was positively
      correlated to both systolic and diastolic blood pressure (P<0.01). After four
      months on insulin, blood pressure returned to pretreatment values or lower
      (P<0.05 to 0.01). Serum sodium also decreased to pretreatment values. No
      significant changes of the flow behaviour of blood were seen after the initiation
      of insulin. CONCLUSIONS: The number of patients was small and the study was not
      primarily designed to examine blood pressure. The preliminary conclusion from the
      present study, however, is that the initiation of insulin treatment in poorly
      controlled type 2 diabetes causes a temporary and possibly clinically significant
      elevation of blood pressure. A change in renal treatment of sodium caused by
      insulin may be one of several possible explanations of the results, but further
      studies are warranted to confirm the findings.

PMID- 22477330
TI  - Occult left ventricular dysfunction diagnosed by myocardial performance index in
      patients with limb girdle muscle dystrophy: A case control study.
AB  - The myocardial performance index (MPI) was assessed in 30 patients with limb
      girdle muscle dystrophy (LGMD) with a normal left ventricular ejection fraction
      (greater than 50%), as well as in 30 age- and sex-matched healthy adults with a
      left ventricular ejection fraction greater than 50%. MPIs derived by pulsed-wave
      Doppler and tissue Doppler were also compared. The MPI was 0.37+/-0.09 in the
      LGMD patients and 0.29+/-0.09 in the control group (P=0.003). These data show
      that patients with LGMD have occult cardiac dysfunction as evidenced by a higher
      MPI than the controls. There was good agreement between the MPIs measured by
      pulsed-wave Doppler and tissue Doppler methods in these patients.

PMID- 22477331
TI  - Suppression of postoperative intimal hyperplasia of vein grafts with edaravone in
      rat models - a scanning electron microscope study.
AB  - PURPOSE: Postoperative intimal hyperplasia, the most common cause of vein graft
      occlusion, is initiated by endothelial injury. In the present study, the
      mechanism by which the free radical scavenger edaravone (Radicut, Mitsubishi
      Tanabe Pharma Co, Japan) protects against endothelial injury in postoperative
      intimal hyperplasia was investigated. METHODS: In 18 male Lewis rats, a right
      epigastric vein graft was interposed into the common femoral artery. Nine rats
      received a pre-operative intraperitoneal administration of edaravone (3.0 mg/kg,
      edaravone group) and the other nine rats received an equal volume of saline
      (saline group). After 1 h, five vein grafts from each group were treated with
      Verhoeff-van Gieson elastica stain and subjected to a histological examination.
      The other four vein grafts from each group were examined with an S-800 Hitachi
      scanning electron microscope (SEM) (Hitachi High-Technologies Co, Japan) at *1000
      magnification, as were three unoperated right epigastric veins (unoperated vein
      group). The endothelial areas of the vein grafts were measured using computerized
      planimetry of the SEM images (ImageJ version 1.37, National Institutes of Health,
      USA). The mean endothelial areas (%) were compared between the two groups.
      RESULTS: Verhoeff-van Gieson elastica stain revealed no significant differences
      between the two groups. SEM showed that endothelial cells in the unoperated
      epigastric vein had a cobblestone-like appearance. In the saline group, the
      endothelial cells were comb-shaped and had adherent monocytes. In the edaravone
      group, however, the cobblestone-like appearance of endothelial cells was well
      preserved, with little monocyte adhesion. Moreover, the mean (+/- standard error
      of the mean) endothelial area was significantly higher in vein grafts from the
      edaravone group than in those from the saline group (74+/-1.8% versus 56+/-4.3%,
      P<0.05), and was similar to those in the unoperated epigastric veins (72+/-1.9%).
      CONCLUSION: These findings show that endothelial injury is present soon after
      placement of the interposition graft. The authors believe that edaravone
      suppresses postoperative intimal hyperplasia by alleviating endothelial injury.

PMID- 22477332
TI  - Arterialized cephalic vein as a femoropopliteal bypass graft: A case report.
AB  - The overall therapeutic strategy in patients with diabetes mellitus and
      peripheral arterial disease affecting several arterial segments is problematic.
      Usually, the greater saphenous vein (GSV) is the gold standard for bypass.
      However, alternative venous grafts may be necessary when the GSV is not
      available. The superficial veins of the arm are not suitable for bypass
      operations in most cases because of anatomical variations, inadequate diameter or
      very thin walls. However, arterialization of the cephalic vein can dilate and
      strengthen the walls, thus avoiding postoperative complications. The present
      patient, whose case was followed for 20 months postoperatively, suffered both
      from diabetes and peripheral arterial disease in a setting of gangrene and a lack
      of the GSV. The treament of the patient and the problems it incurred are
      discussed. The advantages of preoperative temporary arteriovenous shunting to
      improve the quality of the cephalic vein as an alternative autogenous graft are
      analyzed. Currently, the patient has excellent postoperative results, with
      healing of the ulcers and preserved peripheral pulses.

PMID- 22477333
TI  - Chronic mesenteric artery insufficiency produces hyperplasia of the intestine -
      case report.
AB  - Chronic ischemia produces corresponding tissue hypoplasia. However, the present
      paper reports a distinctive hypertrophy of the intestine due to chronic
      mesenteric artery insufficiency. Two patients with chronic mesentery artery
      insufficiency confirmed by angiography are presented. The first patient
      demonstrated marked hypertrophy of the intestine, while the second patient was
      remarkable for pronounced hypoplasia. During the surgery of the first patient, an
      ileum approximately 60 cm long with a sausage-like consistency and cyanosis was
      identified proximal to the cecum; wall-attached thromboembolism material and the
      hypertrophic segment of ileum were removed. In the other patient, the intestine
      wall was paper thin; after the aortomesenteric bypass, the intestine wall grew
      thicker. Postoperative recovery of both patients was uneventful. The commonly
      observed situation after a longstanding hypoxic insult in a setting of chronic
      mesenteric ischemia is that the target tissue will, at least, develop slight
      hypoplasia. However, the cases presented here had either pronounced hyperplasia
      or severe hypoplasia. The authors find this observation so interesting that they
      report it in the hope that an explanation for this conundrum may come forth.

PMID- 22477334
TI  - Leiomyosarcoma of the superior vena cava: Resection with vascular reconstruction 
      case report and review of the literature.
AB  - The present report describes a case of pedunculated intraluminal leiomyosarcoma
      of the superior vena cava, extending to the right atrium, that was successfully
      resected surgically. Superior vena cava reconstruction was performed using bovine
      pericardial graft, saving the sinus node. The pathological variants of this
      neoplasm according to the anatomical site of the tumour are described.

PMID- 22477335
TI  - The contributions of anchoring and past-test performance to the underconfidence
      with-practice effect.
AB  - In the underconfidence-with-practice effect, people's judgments of learning
      (JOLs) typically underestimate memory performance across multiple study-test
      phases. Whereas the past-test hypothesis suggests that this underconfidence stems
      from participants' reliance on earlier test performance to make subsequent JOLs
      (despite new learning), the anchoring hypothesis suggests that the
      underconfidence stems from participants' reliance on a fixed psychological anchor
      point low on the JOL scale to make their JOLs. To contrast the predictions of
      these hypotheses, we had college students study, make JOLs, and test over several
      dozen paired-associate items across two study-test phases. We parametrically
      manipulated the presence or absence of testing and judging within participants
      during Phase 1. Contrary to the past-test hypothesis, items tested during Phase 1
      demonstrated less underconfidence during Phase 2 than did nontested items.
      Furthermore, participants did not increase JOLs from Phase 1 to Phase 2 for items
      that they had not recalled or for items that had not been tested at all,
      suggesting that the underconfidence stemmed largely from participants'
      overreliance on a psychological anchor point to make their JOLs. Past test
      performance, however, seems to be a major cue that participants use to adjust
      their JOLs away from the anchor, reducing underconfidence. This was most evident
      when we used a between-participants manipulation (Exp. 2) to cause our
      participants to anchor their JOLs either high or low on the JOL scale, producing
      differential underconfidence independent of any adjustment. Taken together, these
      results support the anchoring hypothesis over the past-test hypothesis for
      explaining underconfidence with practice.

PMID- 22477336
TI  - Semantic similarity influences early morphological priming in Serbian: a
      challenge to form-then-meaning accounts of word recognition.
AB  - Semantically similar (e.g., coolant-COOL) primes have produced greater
      facilitation than have form-similar but semantically dissimilar (e.g., rampant
      RAMP) primes when English words have appeared in the forward-masked primed
      lexical decision task (Feldman, O'Connor, & Moscoso del Prado Martin, Psychonomic
      Bulletin & Review 16: 684-691, 2009). These results challenge claims that form
      based, semantically blind activation underlies early morphological facilitation.
      Some have argued that the English materials in previous studies were not ideally
      constructed, insofar as the types of spelling changes to affixed stems differed
      in the semantically similar and dissimilar pairs. The present study exploited
      Serbian's bialphabetism, rich morphology, and homographic (form-identical) stems
      to replicate early effects of semantic similarity. Furthermore, it incorporated
      within-target manipulations of prime type and of alphabet, such that the
      alphabets of the prime-target pairs matched in Experiment 1a and alternated in
      Experiment 1b. Importantly, no letter or phoneme changes occurred between the
      stems of the primes and targets. These results revealed significant effects of
      semantic similarity that are comparable with and without alphabet alternation.
      The semantic effects in Serbian replicated almost exactly those in English
      (Feldman et al., Psychonomic Bulletin & Review 16: 684-691, 2009), which suggests
      that even early in the course of processing, morphemes are units of meaning as
      well as of form. The results failed to support models of lexical processing that
      postulate sequential access, first to the morphological form, and then to the
      semantic aspects of words.

PMID- 22477337
TI  - Ezrin overexpression by transformed human ovarian surface epithelial cells,
      ovarian cleft cells, and serous ovarian adenocarcinoma cells.
AB  - OBJECTIVES: We have shown that ezrin expression correlates with ovarian
      epithelial cancer (OVCA) cell proliferation and metastatic behavior. In this
      study, we evaluated ezrin expression in transformed ovarian superficial
      epithelial cells (OSE) in ovarian clefts and in culture. STUDY DESIGN:
      Immunohistochemistry and Western blotting for immunoreactive ezrin (ir-ezrin) in
      normal ovarian tissue, cultured OSE, and ovarian epithelial cancer cells.
      RESULTS: While ir-ezrin was not demonstrable in normal cuboidal surface cells or
      interior ovarian organelles, cells lining the ovarian clefts strongly expressed
      ir-ezrin. Long-term culture of OSE increased ezrin expression and cytological
      abnormalities. Administration of estradiol and insulin at levels reported in
      inclusions dramatically induced OSE ir-ezrin expression to OVCA levels and
      membrane specializations; ruffling, pseudopodia and filopodia. Moreover epidermal
      growth factor (EGF) drastically increased ezrin translocation in OSE cells in a
      time-dependent manner. CONCLUSIONS: Ezrin expression by OSE increases during
      transformation. Ezrin expression is responsive to estradiol and growth factors
      previously shown to be present in ovarian inclusions. These findings suggest that
      the microenvironment in ovarian inclusions and clefts contributes to the
      development of OVCA. Our findings elaborate on the mechanism of the ovarian
      origin of OVCA.

PMID- 22477339
TI  - Editorial.

PMID- 22477338
TI  - Activin A stimulates interleukin 8 and vascular endothelial growth factor release
      from cultured human endometrial stromal cells: possible implications for the
      pathogenesis of endometriosis.
AB  - BACKGROUND: Activin A is an endometrial secretory product involved in
      inflammation and angiogenesis. The present study aimed to evaluate the effect of
      activin A and its antagonist follistatin on interleukin (IL)-6, IL-8, and
      vascular endothelial growth factor (VEGF) expression and release from cultured
      human endometrial stromal cells (HESCs) from women with and without
      endometriosis. METHODS: The HESCs were collected from women with endometriosis (n
      = 6) and controls (n = 6). Primary cultures were treated with activin A at
      different doses or activin A plus follistatin. The IL-6, IL-8, and VEGF messenger
      RNA expression was evaluated by real-time polymerase chain reaction and protein
      release was evaluated by enzyme-linked immunosorbent assay. RESULTS: Unstimulated
      HESC from women with endometriosis secreted more IL-6 and IL-8 than controls. The
      addition of activin A increased IL-8 and VEGF secretion in HESC from controls and
      decreased IL-6 and IL-8 secretion in HESC from women with endometriosis. These
      effects were counteracted by follistatin. CONCLUSION: Activin A regulates the
      expression and secretion of IL-8 and VEGF in cultured HESC, and this mechanism
      appears to be disrupted in eutopic endometrial cells from women affected by
      endometriosis.

PMID- 22477340
TI  - Rudimentary Reading Repertoires via Stimulus Equivalence and Recombination of
      Minimal Verbal Units.
AB  - We report a study with sixteen low-SES Brazilian children that sought to
      establish a repertoire of relations involving dictated words, printed words, and
      corresponding pictures. Children were taught: (1) in response to dictated words,
      to select corresponding pictures; (2) in response to syllables presented in both
      visual and auditory formats, to select words which contained a corresponding
      syllable in either the first or the last position; (3) in response to dictated
      word samples, to "construct" corresponding printed words via arranging their
      constituent syllabic components; and (4) in response to printed word samples, to
      construct identical printed words by arranging their syllabic constituents. After
      training on the first two types of tasks, children were given tests for
      potentially emergent relations involving printed words and pictures. Almost all
      exhibited relations consistent with stimulus equivalence. They also displayed
      emergent naming performances--not only with training words but also with new
      words that were recombinations of their constituent syllables. The present work
      was inspired by Sidman's stimulus equivalence paradigm and by Skinner's
      functional analysis of verbal relations, particularly as applied to conceptions
      of minimal behavioral units and creativity (i.e., behavioral flexibility) in the
      analytical units applied to verbal relations.

PMID- 22477341
TI  - Generalized negatively reinforced manding in children with autism.
AB  - Individuals with developmental disabilities are often unable to influence their
      social environment in traditional ways (i.e., vocal language) and frequently
      exhibit challenging behaviors (e.g., aggression and self-injury) because such
      behaviors were previously reinforced under similar conditions. While the area of
      positive reinforcement manding has been well-documented and empirically
      validated, there is less research in the area of negatively reinforced manding
      particularly in the area of negatively reinforced manding of nonpreferred items.
      Using a multiple baseline design across participants, this study sought to teach
      three children with autism to replace their challenging behaviors with more
      socially appropriate ways to request the removal of nonpreferred items. Results
      showed that all participants were able to learn the negatively reinforced mand
      response and these mand responses were generalized to other untrained items. In
      addition to extending the research in the area, the study empirically defined a
      procedure for teaching negatively reinforced manding of nonpreferred items.
      Moreover, teaching the mand response resulted in quality of life improvements for
      all participants and their families.

PMID- 22477342
TI  - Empirical Applications of Skinner's Analysis of Verbal Behavior with Humans.
AB  - In Verbal Behavior,Skinner (1957) provided a conceptual framework and taxonomy
      for the controlling variables of language that defined independent verbal
      operants by their functional relations to antecedents and consequences (rather
      than by topography or meaning). Although professional interest in this area has
      recently increased within the behavior analytic community, Skinner's conceptual
      framework may not yet have fully impacted the experimental literature. This
      quantitative review of the literature examined the studies on verbal behavior
      that were empirical in nature, concerned with human verbal behavior, and
      addressed at least one verbal operant (e.g., mand, tact, echoic, autoclitic,
      and/or intraverbal behavior) within the experiment. The results of this review
      suggest that a growing body of research exists to support many of the tenets of
      Skinner's conceptualization and taxonomy but many areas of verbal behavior
      research have yet to be addressed. Continued research in this area is crucial for
      the development and implementation of effective verbal behavior interventions for
      people with disabilities.

PMID- 22477343
TI  - Behavioral language interventions for children with autism: comparing applied
      verbal behavior and naturalistic teaching approaches.
AB  - Several important behavioral intervention models have been developed for teaching
      language to children with autism and two are compared in this paper.
      Professionals adhering to Skinner's conceptualization of language refer to their
      curriculum and intervention programming as applied verbal behavior (AVB). Those
      primarily focused on developing and using strategies embedded in natural settings
      that promote generalization refer to their interventions as naturalistic teaching
      approaches (NTAs). The purpose of this paper is to describe each approach and
      discuss similarities and differences in terms of relevant dimensions of stimulus
      control. The discussion includes potential barriers to translation of terminology
      between the two approaches that we feel can be overcome to allow better
      communication and collaboration between the two communities. Common naturalistic
      teaching procedures are described and a Skinnerian conceptualization of these
      learning events is provided.

PMID- 22477344
TI  - An implementation of protocol analysis and the silent dog method in the area of
      behavioral safety.
AB  - Recent research has demonstrated that conducting safety observations increases
      the safety performance of the observer. The purpose of this study was to help
      determine whether observers make self-verbalizations regarding their own safety
      performance and whether these reports are functionally related to safety
      performance. In order to answer these questions two experiments were conducted
      using both protocol analysis and the silent dog method. The objective of
      Experiment 1 was (a) to determine whether safety performance with continuous,
      concurrent talk-aloud procedures is functionally equivalent to safety performance
      without talk-aloud reports, and (b) to determine whether that safety performance
      is altered when participants are presented with a distracter task. The goal of
      Experiment 2 was to determine whether the safety-related verbalizations made by
      Experiment 1 participants were task-relevant and functionally related to safety
      performance. The results from both Experiments 1 and 2 provide support for the
      existence of a functional relationship between safety-related verbalizations and
      increases in safety performance.

PMID- 22477345
TI  - The effects of a stimulus-stimulus pairing procedure on the unprompted
      vocalizations of a young child diagnosed with autism.
AB  - The current study evaluated the effects of a stimulus-stimulus pairing procedure
      intended to increase spontaneous vocalizations of a young child diagnosed with
      autism. A multiple-baseline design across two target phonemes was used to
      evaluate the effects of the pairing procedure on the frequency of phonemes
      uttered by the participant. Data were collected during presession, postsession,
      and follow-up periods across three conditions: Baseline, Control, and Pairing.
      During the Pairing conditions, a target phoneme was repeatedly vocalized by the
      experimenter and was systematically paired with preferred stimuli. Results from
      postsession observations following the pairing condition evidenced no increase in
      the target sounds. Practical and theoretical implications of the results are
      discussed.

PMID- 22477346
TI  - Words as behavior.

PMID- 22477347
TI  - Antecedents and consequences of words.
AB  - As instances of behavior, words interact with environments. But they also
      interact with each other and with other kinds of behavior. Because of the
      interlocking nature of the contingencies into which words enter, their behavioral
      properties may become increasingly removed from nonverbal contingencies, and
      their relationship to those contingencies may become distorted by the social
      contingencies that maintain verbal behavior. Verbal behavior is an exceedingly
      efficient way in which one organism can change the behavior of another. All other
      functions of verbal behavior derive from this most basic function, sometimes
      called verbal governance. Functional verbal antecedents in verbal governance may
      be extended across time and space when individuals replicate the verbal behavior
      of others or their own verbal behavior. Differential contact with different
      verbal antecedents may follow from differential attention to verbal stimuli
      correlated with consequential events. Once in place, verbal behavior can be
      shaped by (usually social) consequences. Because these four verbal processes
      (verbal governance, replication, differential attention, and verbal shaping)
      share common stimulus and response terms, they produce interlocking contingencies
      in which extensive classes of behavior come to be dominated by verbal
      antecedents. Very different consequences follow from verbal behavior depending on
      whether it is anchored to environmental events, as in scientific verbal
      practices, or becomes independent of it, as in religious fundamentalism.

PMID- 22477348
TI  - Toward an "Awareness" of the Relationship between Task Performance and Own Verbal
      Accounts of that Performance.
AB  - The existence of learning without awareness has been debated for many years.
      Learning without awareness is said to occur when an individual's behavior has
      been affected without that individual being aware of the conditions affecting the
      behavior, of the relationship between those conditions and the behavior, or of
      the fact that the behavior has changed. This paper describes a series of
      experiments investigating this phenomenon. The findings support the existence of
      "learning without awareness." However, it is argued that the term "awareness"
      should be discarded as it is misleading. Instead, the results of the experiments
      are discussed in terms of behavior for which the individual does not provide a
      complete verbal account.

PMID- 22477349
TI  - A Summary and Commentary on D. and S. Premack's Original Intelligence.

PMID- 22477350
TI  - Joint Control for Dummies*: An Elaboration of Lowenkron's Model of Joint
      (Stimulus) Control.
AB  - The following paper describes Lowenkron's model of joint (stimulus) control.
      Joint control is described as a means of accounting for performances, especially
      generalized performances, for which a history of contingency control does not
      provide an adequate account. Examples are provided to illustrate instances in
      which joint control may facilitate performance of a task.

PMID- 22477351
TI  - An introduction to joint control.
AB  - Lowenkron and colleagues (Lowenkron, 1984; 1991; 1998; 2006; Lowenkron and
      Colvin, 1992) describe a model that explains complex behavior using only well
      established behavioral principles, concepts and terms. The model, called joint
      control, is especially useful for understanding complex and delayed
      discriminations within a purely behavioral framework and with no appeal to
      hypothetical concepts or structures. In it the listener is an active behaver
      rather than a processor of information. In fact, on this account the listener
      becomes a speaker. Several examples of the relevance of this approach to the
      explanation of complex behavior are provided, including cases of stimulus
      selection, conditional discrimination, and generalized identity matching.

PMID- 22477352
TI  - Joint control and the selection of stimuli from their description.
AB  - This research examined the role the two constituents of joint control, the tact
      and the echoic, play in producing accurate selections of novel stimuli in
      response to their spoken descriptions. Experiment 1 examined the role of tacts.
      In response to unfamiliar spoken descriptions, children learned to select from
      among six successively presented comparisons which varied in their color, shape,
      and border features. Repeated testing and training revealed that accurate
      selecting with new combinations of the same colors, shapes and borders, did not
      occur until after the children could themselves tact the individual color, shape
      and border features with the unfamiliar descriptions. Experiment 2 examined the
      role of self-echoics. Here, the stimulus features were given their familiar
      names, but the rehearsal of these names, while searching among the six
      successively presented comparisons, was impeded by a distracter task. Under these
      conditions selection of the correct comparison was found to depend on its
      position in the order of presentation. Correct comparisons presented earlier in
      the order, and presumably less effected by the distracter task, were more likely
      to be selected than correct comparisons presented later in the serial order.
      Taken together, these data suggest that generalized stimulus selection must be
      under joint tact/echoic control. The data also illustrate the distinction between
      mediated selection of a stimulus in response to its description (i.e., selection
      under joint control) and the traditional conception of an unmediated selection
      response evoked as a result of a heightened response probability in a conditional
      discrimination.

PMID- 22477353
TI  - The role of modeling and automatic reinforcement in the construction of the
      passive voice.
AB  - Language acquisition has been a contentious topic among linguists,
      psycholinguists, and behaviorists for decades. Although numerous theories of
      language acquisition have surfaced, none have sufficiently accounted for the
      subtleties of the language that children acquire. The present study attempts to
      explain the role of modeling and automatic reinforcement in the acquisition of
      the passive voice. Six children, ages 3 to 5, participated in this study. The
      results indicated that the children began using the passive voice only after the
      experimenter modeled passive sentences. Furthermore, the usage of the passive
      voice increased with repeated exposure to the experimenter's verbal behavior.
      Given that the children were not explicitly reinforced, it is proposed that their
      behavior was automatically reinforced for using the passive voice.

PMID- 22477354
TI  - Generalization of relational matching to sample in children: a direct
      replication.
AB  - The ability of preschool age children to perform generalized relational matching
      to sample tasks with and without an overt mediating stimulus was examined. This
      experiment was a direct replication of a study by Lowenkron (1984) and examined a
      behavioral model relevant to complex human behavior that he later came to call
      joint control. Children were trained to code two-dimensional stimuli with the
      help of a handheld mediating stimulus. They were later tested for generalization
      of relational matching to sample with and without the mediating stimulus. Results
      indicated high levels of generalized matching to sample with the mediating
      stimulus and lower levels without. Findings also indicated that generalization
      was somewhat stronger with symmetrical shapes than with asymmetrical. Results are
      discussed in terms of a radical behavioral interpretation of complex human
      behavior.

PMID- 22477355
TI  - The role of rehearsal in joint control.
AB  - Behavior analysts have offered accounts of the behavior involved in matching to
      sample and delayed matching to sample. But until recently have not offered a
      behavioral analysis of generalized matching-to-sample. The concept of joint
      control, however, seems especially suited to such an analysis The present study
      used a joint-control procedure to train five adult women to acquire a generalized
      sequencing behavior using an unfamiliar language. After joint-control training
      the participants were able to produce untrained picture sequences, and blocking
      the mediating response during the sequencing task resulted in a reduction in the
      number of accurate sequences. These results clearly support response mediation as
      a precurrent to various kinds of complex human behavior.

PMID- 22477356
TI  - The Role of Joint Control in the Manded Selection Responses of Both Vocal and Non
      vocal Children with Autism.
AB  - In the present study, joint-control training was applied when teaching manded
      selection responses to children with autism. Four vocal children with autism
      participated in the first experiment, two males (ages seven and eight) and two
      females (ages seven and nine). The results showed that it was only after object
      word naming was trained under joint control that the symmetrical performance of
      manded selection responses appeared with no additional training. Four non-vocal
      children with autism participated in the second experiment, two males (ages six
      and seven), and two females (ages twelve and thirteen). These results also showed
      that it was only after the joint tact/self-mimetic/sequelic control training that
      the symmetrical performance of manded selection responses appeared with no
      additional training.

PMID- 22477357
TI  - Joint control: a discussion of recent research.
AB  - The discrimination of the onset of joint control is an important interpretive
      tool in explaining matching behavior and other complex phenomena, but the
      difficulty of getting experimental control of all relevant variables stands in
      the way of a definitive experiment. The studies in the present issue of The
      Analysis of Verbal Behavior illustrate how modest experiments can take their
      place in a web of interpretation to make a strong case that joint control is a
      necessary element of such phenomena.

PMID- 22477358
TI  - Scene findings and autopsy features in a case of ultra-light aircraft crash.

PMID- 22477359
TI  - Lethal hemorrhage from a ureteric-arterial-enteric fistula diagnosed by
      postmortem CT angiography.
AB  - Fistula formation following pelvic surgery and radiotherapy, including ureteric
      arterial fistulas (UAF), is well documented, however, ureteric-arterial-enteric
      fistula is extremely rare. Conventional autopsy is usually required for the
      definitive diagnosis of pelvic vascular fistulas although an accurate diagnosis
      can still be complicated and challenging. The role of post-mortem computed
      tomography (PMCT) as an adjunct to conventional autopsy is well documented in the
      literature. One of the limitations of PMCT is the diagnosis of vascular
      conditions. Post-mortem computed tomography angiography (PMCTA) is a recently
      introduced technique that can assist in detecting such pathology. We present a
      case of post-radiotherapy ureteric-arterial-enteric fistula presenting as massive
      rectal and vaginal bleeding diagnosed prior to autopsy on PMCTA. The role of
      PMCTA in the diagnosis of such a UAF has not previously been reported in the
      literature.

PMID- 22477360
TI  - Functional outcomes in schizophrenia: employment status as a metric of treatment
      outcome.
AB  - The importance of an adequate and satisfying level of functioning for the course
      and outcome of schizophrenia has been increasingly emphasized by researchers in
      recent years. Employment status is a major component of the patient's functioning
      and is generally believed to be essential for well-being, satisfaction in life,
      and a better prognosis for schizophrenia illness. This article summarizes recent
      relevant publications concerning the employment status of schizophrenia patients
      and its influence on treatment outcome. Given the significant link between
      employment status and outcome in schizophrenia, different influencing factors of
      employment are discussed, as they mirror potential treatment targets. Finally,
      currently available treatment strategies for the improvement of employment status
      are outlined.

PMID- 22477361
TI  - Induction of cell proliferation in old rat liver can reset certain gene
      expression levels characteristic of old liver to those associated with young
      liver.
AB  - During the past decade, it has become increasingly clear that consistent changes
      in the levels of expression of a small cohort of genes accompany the aging of
      mammalian tissues. In many cases, these changes have been shown to generate
      features that are characteristic of the senescent phenotype. Previously, a small
      pilot study indicated that some of these changes might be reversed in rat liver,
      if the liver cells became malignant and were proliferating. The present study has
      tested the hypothesis that inducing proliferation in old rat liver can reset the
      levels of expression of these age-related genes to that observed in young tissue.
      A microarray approach was used to identify genes that exhibited the greatest
      changes in their expression during aging. The levels of expression of these
      markers were then examined in transcriptomes of both proliferating hepatomas from
      old animals and old rat liver lobes that had regenerated after partial
      hepatectomy but were again quiescent. We have found evidence that over 20 % of
      the aging-related genes had their levels of expression reset to young levels by
      stimulating proliferation, even in cells that had undergone a limited number of
      cell cycles and then become quiescent again. Moreover, our network analysis
      indicated alterations in MAPK/ERK and Jun-N-terminal kinase pathways and the
      potential important role of PAX3, VCAN, ARRB2, NR1H2, and ITGA5 that may provide
      insights into mechanisms involved in longevity and regeneration that are distinct
      from cancer.

PMID- 22477362
TI  - Altered white matter structure of the dentatorubrothalamic pathway in children
      with autistic spectrum disorders.
AB  - Neuropathological studies have demonstrated decreased Purkinje cells in
      cerebellar cortex and changes in the dentate nucleus of the cerebellum, the
      projection target for the Purkinje cells, in autistic spectrum disorders (ASD).
      The dentatorubrothalamic tract is formed by efferents from the dentate nucleus
      projecting toward the red nucleus with axon collaterals to this nucleus and
      continuing to innervate the ventral lateral and ventral anterior nuclei of the
      thalamus. In the current study, we assessed whether the dentatorubrothalamic
      tract is altered in ASD using Q-ball imaging (QBI). The QBI tractography was
      performed in 13 children with high functioning ASD (HFA), 11 children with low
      functioning ASD (LFA), and 14 typically developing children (TD). Regions of
      interest in dentate nucleus and red nucleus in both hemispheres were objectively
      placed to sort bilateral dorsal-rostral (DR), dorsal-caudal (DC), ventral-rostral
      (VR), and ventral-caudal (VC) portions of the dentatorubrothalamic pathway. Group
      differences in fractional anisotropy (FA), axial diffusivity, radial diffusivity,
      and fiber volume of individual pathways were analyzed. Significantly reduced FA
      was found in children with LFA and HFA, compared to the TD group in tracts
      originating in all four subdivisions of the right dentate nucleus. Tract-based
      morphometry (TBM) analysis demonstrated significant reductions of FA in caudal
      midbrain (p<0.0001), dorsal-caudal dentate (p=0.0013), and ventral-caudal dentate
      (p=0.0061) on the right in the LFA group. The FA values in TBM segments of right
      VR and VC pathways were significantly correlated with communication skills in the
      combined HFA/LFA group, while there was a significant correlation found between
      TBM segments of right DR pathway and daily living skills (r=0.76; p=0.004).
      Decreased white matter integrity in dorsal portions of the dentatorubrothalamic
      tract may be related to motor features in ASD, while changes in the ventral
      portions are related more to communication behavior.

PMID- 22477363
TI  - Subcellular distribution of patched and smoothened in the cerebellar neurons.
AB  - The Sonic hedgehog (Shh) signaling pathway carries out a wide range of biological
      functions such as patterning of the embryonic neural tube and expansion of
      cerebellar granule cell precursors. We previously have found that the Shh
      signaling receptors, Patched1 (Ptch1) and Smoothened (Smo), are expressed in
      hippocampal neurons of developing and adult rats, suggesting the continued
      presence of Shh signaling in postmitotic, differentiated neurons. Here, we report
      that Ptch1 and Smo are present in the processes and growth cones of immature
      neurons in the developing cerebellum, and that, in the mature cerebellum, Ptch1
      and Smo are expressed by several types of neurons including Purkinje cells,
      granule cells, and interneurons. Within these neurons, Ptch1 and Smo are
      predominantly localized in the postsynaptic side of the synapses, a distribution
      pattern similar to that found in hippocampal neurons. Our findings provide
      morphological evidence that Shh signaling events are not confined to neuronal
      precursors and are likely to have ongoing roles within the postmitotic neurons of
      the developing and adult cerebellum.

PMID- 22477364
TI  - Early onset scoliosis: current concepts and controversies.
AB  - Early Onset Scoliosis (EOS) may be associated with long-term pulmonary morbidity,
      which is not commonly seen in Adolescent Idiopathic Scoliosis. Initial evaluation
      is based on determining any underlying etiology related to congenital or
      syndromic conditions. Assessing the impact of scoliosis on thoracic development
      may help guide treatment, which is often required at a young age in these
      children to prevent irreversible pulmonary insufficiency. Treatment is based on
      multiple factors but may include non-surgical strategies, such as casting or
      bracing, along with growth-sparing surgical procedures using growing rods or
      chest wall expansion. Definitive fusion is rarely indicated in young patients.
      This chapter will cover the diagnosis, evaluation, and treatment of children with
      EOS.

PMID- 22477365
TI  - Staying the course.....

PMID- 22477367
TI  - The use of retrievable inferior vena cava filters in the trauma population.
AB  - OBJECTIVE: To determine if the use of retrievable filters resulted in an increase
      in the placement of inferior vena cava (IVC) filters in trauma patients. DESIGN:
      All patients who underwent IVC filter placement at Yale-New Haven Hospital, New
      Haven, Connecticut, USA between the years 1999 and 2004. SETTING: Academic, level
      1 trauma centre. PATIENTS: Included in the present study were 202 trauma patients
      and 676 nontrauma patients. INTERVENTION: IVC filter placement. MAIN OUTCOME
      MEASURE: Demographics, indications, complication rates and type of IVC filters
      placed in trauma patients versus nontrauma patients were evaluated. RESULTS: The
      present study determined 45.4% (n=92) of trauma patients undergoing IVC filter
      placement were younger than 40 years of age, compared with 7.8% (n=53) of
      nontrauma patients. The most common indication for IVC filter placement in trauma
      patients was prophylaxis (n=162, 80.2%), while in the nontrauma patients only
      11.4% (n=77) of patients underwent prophylactic filter placement. The number of
      retrievable filters used in trauma patients increased from 46.7% in 2001, the
      year they became available, to 78.9% in 2004. The use of retrievable filters
      similarly increased in the nontrauma population from 35.9% in 2001 to 78.3% in
      2004. Approximately 24% of the patients that underwent IVC filter placement at
      Yale-New Haven Hospital were categorized as trauma patients. The complication
      rate for this time period was 0.5% (n=1) in the trauma population versus 3.7%
      (n=26) in the nontrauma population. CONCLUSION: The overall number of IVC filters
      placed in trauma patients did not dramatically increase with the introduction of
      retrievable filters, suggesting that the indications for the use of IVC filters
      have not changed.

PMID- 22477368
TI  - Serum biochemical changes in rabbits on a regular diet with and without flax
      lignan complex following a high-cholesterol diet.
AB  - BACKGROUND: Flax lignan complex (FLC) isolated from flaxseed suppresses
      development of hypercholesterolemic atherosclerosis. It does not produce
      regression of atherosclerosis, but prevents its regular diet-induced acceleration
      following a high-cholesterol diet. It is not known if replacement of a high
      cholesterol diet with a regular diet has deleterious effects on body organs.
      OBJECTIVES: To determine if short-term use of a high-cholesterol diet, and a
      regular diet with or without FLC following the high-cholesterol diet, have any
      adverse effects on serum electrolytes, glucose and enzymes related to the liver,
      kidneys, skeletal muscle and intestines. METHODS: Blood samples were collected
      from the rabbits before and at various intervals during the high-cholesterol
      diet, and while on the regular diet with or without FLC, following the high
      cholesterol diet. Measurements of serum total cholesterol, glucose, aspartate
      aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase
      (ALT), gamma-glutamyltransferase (GGT), albumin, creatinine, electrolytes (sodium
      [Na], potassium [K], chloride [Cl]) and carbon dioxide (CO(2)) were taken.
      RESULTS: The high-cholesterol diet produced hypercholesterolemia, which was
      associated with reductions in serum glucose and no significant changes in serum
      Na, K, Cl, CO(2), ALT, ALP, AST, GGT, albumin or creatinine. Regular diet with or
      without FLC, following the high-cholesterol diet, reduced serum total cholesterol
      and glucose, increased serum Na, Cl and creatinine, but produced no significant
      alterations in serum K, CO(2), ALT, AST, GGT or albumin. FLC reduced serum ALP,
      but regular diet produced no significant change. CONCLUSION: Short-term use of a
      high-cholesterol diet, or a regular diet with or without FLC following the high
      cholesterol diet, does not produce deleterious effects in the liver, kidneys,
      skeletal muscle, intestine or bone, as shown by changes in serum electrolytes,
      glucose and enzymes.

PMID- 22477369
TI  - Functional outcome after femoral endarterectomy: A single-centre experience.
AB  - OBJECTIVE: To assess limb salvage and functional outcome in patients who
      underwent femoral endarterectomy (FE). METHODS: A single-centre, retrospective
      analysis of all patients undergoing FE in the past four years. RESULTS: FE was
      performed on 30 patients (32 symptomatic legs) to treat gangrene (n=5), pain at
      rest (n=7) and incapacitating intermittent claudication (n=20). Patients had a
      mean age of 76.2 years. Twenty-three FEs were performed electively and nine were
      emergency procedures. Twenty-two patients were operated on under general
      anesthesia, five under local anesthesia and three under spinal/epidural
      anesthesia. Forty-six per cent of the patients underwent a simultaneous
      revascularization procedure (33% profundaplasty, 3% femoral-femoral cross-over,
      3% femoral-popliteal and 3% aorto-bifemoral bypass). Overall patency rate and
      limb salvage rate was 80% and 74%, respectively, at mean follow-up of 25 months.
      Early mortality was 6% and morbidity was 24%. Among the living patients, 88% were
      happy with their quality of life and rated the procedure excellent, 6% rated the
      procedure as good and 6% rated the procedure as bad. CONCLUSION: The functional
      outcome of FE is very favourable, either as a primary or adjunctive procedure
      where angioplasty is not possible. FE can be performed under locoregional
      anesthesia, which is potentially suitable in elderly patients to avoid major
      amputation and its associated sequelae.

PMID- 22477370
TI  - Early thrombosis in bovine mesenteric vein grafts after infrainguinal
      reconstruction.
AB  - INTRODUCTION: Autologous vein grafts are still the gold standard in infrainguinal
      arterial bypass grafting procedures. However, due to the unavailability of
      suitable autologous vein grafts, heterogeneous grafts are usually preferred. In
      the present study, surgical outcomes with bovine mesenteric vein grafts (ProCol,
      Hancock Jaffe Laboratories, USA) in the infrainguinal location in patients with
      ischemic leg infection or necrosis are presented. METHODS: Seven patients who
      underwent infrainguinal arterial reconstructions with ProCol grafts were
      evaluated retrospectively. RESULTS: Graft thrombosis was seen in two patients on
      postoperative day 1 (28.5%). The shortest and the longest patency durations were
      six and 18 months, respectively. Aneurysmal dilation developed postoperatively in
      two grafts (28.5%) after 12 and 18 months, respectively. CONCLUSION: In cases
      where infection accompanies ischemia, and autologous veins are not available as
      graft materials, ProCol grafts can be used as temporary grafts in infrainguinal
      arterial reconstructions. The use of the graft is believed to be unacceptable for
      any indication other than infection due to its low short- and long-term patency
      rates and high risk of aneurysm formation in this location.

PMID- 22477366
TI  - The antihypertensive effect of arginine.
AB  - Hypertension is a leading cause of morbidity and mortality worldwide. Individuals
      with hypertension are at increased risk of stroke, heart disease and kidney
      failure. Although the etiology of essential hypertension has a genetic component,
      lifestyle factors such as diet play an important role. Reducing dietary salt is
      effective in lowering blood pressure in salt-sensitive individuals. Insulin
      resistance and altered glucose metabolism are common features of hypertension in
      humans and animal models, with or without salt sensitivity. Altered glucose
      metabolism leads to increased formation of advanced glycation end products.
      Insulin resistance is also linked to oxidative stress, and alterations in the
      nitric oxide pathway and renin angiotensin system. A diet rich in protein
      containing the semiessential amino acid, arginine, and arginine treatment, lowers
      blood pressure in humans and in animal models. This may be due to the ability of
      arginine to improve insulin resistance, decrease advanced glycation end products
      formation, increase nitric oxide, and decrease levels of angiotensin II and
      oxidative stress, with improved endothelial cell function and decreased
      peripheral vascular resistance. The Dietary Approaches to Stop Hypertension
      (DASH) study demonstrated that the DASH diet, rich in vegetables, fruits and low
      fat dairy products; low in fat; and including whole grains, poultry, fish and
      nuts, lowered blood pressures even more than a typical North American diet with
      similar reduced sodium content. The DASH diet is rich in protein; the blood
      pressure-lowering effect of the DASH diet may be due to its higher arginine
      containing protein, higher antioxidants and low salt content.

PMID- 22477371
TI  - Complete fracture of an Ikari guiding catheter in the axillary artery during
      transradial coronary intervention.
AB  - Complete fracture of a guiding catheter during percutaneous coronary intervention
      is an exceedingly rare but potentially serious complication. The present case
      report describes the complete fracture of an Ikari guiding catheter and the
      various manoeuvres used to retrieve the broken catheter fragment. The anatomy and
      limited space in the radial and axillary arteries made it possible for the
      catheter to twist on itself during a difficult cannulation, resulting in its
      complete fracture and separation. The present case highlights the need for
      caution in the manipulation of an Ikari guiding catheter by the transradial
      approach.

PMID- 22477373
TI  - Use of nesiritide in Ebstein's anomaly.
AB  - A rare case of a 77-year-old man with congestive heart failure due to a
      previously diagnosed condition of Ebstein's anomaly is presented. Unique to the
      present case is the treatment of New York Heart Association class IV congestive
      heart failure associated with Ebstein's anomaly with nesiritide.

PMID- 22477372
TI  - Superior vena cava syndrome: A medical emergency?
AB  - Superior vena cava (SVC) syndrome was originally described as being secondary to
      an infection. Currently, it is almost exclusively secondary to malignancy. A case
      of SVC syndrome presenting with dyspnea, facial swelling, neck distension and
      cough developed over a period of 10 days is reported. The approach included
      imaging studies and tissue diagnosis. Computed tomography scan of the chest
      revealed a lobulated mass on the right upper chest invading the mediastinum, and
      cytology obtained from bronchoscopy revealed squamous cell carcinoma. The
      etiology, diagnosis and treatment modalities of the SVC syndrome are discussed.

PMID- 22477374
TI  - Fatal cerebellar stroke following emergency endovascular stent grafting of a
      leaking thoracic aortic aneurysm: A case report.
AB  - Stent-grafting of thoracic aortic diseases has developed as an alternative
      therapeutic modality in thoracic aneurysm management. Postprocedural
      complications include mortality, endoleaks, paraplegia and stroke. Other
      complications that may arise in cases of overstenting the origin of the left
      subclavian arther include left upper limb ischemia, subclavian steal syndrome and
      stroke. Posterior circulation strokes due to vertebral artery insufficiency have
      been reported in the past. In the present case, a fatal stroke caused by a
      cerebellar infarct culminating in the death of a patient with a leaking thoracic
      aortic aneurysm is reported. Medical personnel as well as patients should be
      aware of this possible complication. Vigilance in assessing the contralateral
      cerebral circulation before the procedure is a prerequisite in less acute
      circumstances.

PMID- 22477375
TI  - Editorial.

PMID- 22477376
TI  - Stimulus-stimulus pairing and subsequent mand acquisition of children with
      various levels of verbal repertoires.
AB  - Effects of a stimulus-stimulus pairing procedure on the subsequent acquisition of
      mand operants were investigated. An attempt was made to shape novel sounds that
      emerged through the pairing procedure into a mand. Six children, aged two to five
      years, with moderate to severe language and communication delays, participated.
      Two conditions were used following the pairing condition: postpairing and direct
      reinforcement. The emergence of mands was compared across these conditions. An
      additional analysis was made of the relation between participants' baseline
      verbal repertoires and the effects of the pairing and the emergence of mands.
      Results indicate the possibility of stimulus control from a stimulus-stimulus
      pairing to mand as shown in two of the participants who had demonstrated high
      rates of vocal play and low to no verbal repertoire prior to this study. Target
      vocal sounds during postpairing and direct reinforcement condition remained at
      zero to low levels for participants with high verbal repertoire and little vocal
      play, warranting future studies on relations between the pre-existing verbal
      repertoire and the effectiveness of stimulus-stimulus pairing.

PMID- 22477377
TI  - Some issues in infant speech perception: do the means justify the ends.
AB  - A major focus of research on language acquisition in infancy involves
      experimental studies of the infant's ability to discriminate various kinds of
      speech or speech-like stimuli. This research has demonstrated that infants are
      sensitive to many fine-grained differences in the acoustic properties of speech
      utterances. Furthermore, these empirical findings have led investigators to
      theorize about how the infants internally process and represent speech stimuli.
      This paper examines one particular experimental protocol frequently used in these
      experiments: the Head-Turn Preference Procedure. It will be shown that this
      procedure is methodologically flawed and the theoretical conclusions drawn from
      its results are not adequately warranted.

PMID- 22477378
TI  - An underdiscussed aspect of chomsky (1959).
AB  - Chomsky's (1959) review of Skinner's (1957)Verbal Behavior has been influential
      and attributed with a role in the cognitive revolution. However, while counter
      reviews from within behavior analysis have noted that Chomsky misunderstood the
      subject matter, certain aspects of his scholarship have been underdiscussed. This
      includes several instances where Chomsky misquotes Skinner or takes his quotes
      out of context. Similar to the findings of Sokal (1996a, 1996b), it is speculated
      that the problems with Chomsky were overlooked by cognitive psychologists because
      his general outlook was accepted. Implications for the editorial review process
      are discussed.

PMID- 22477379
TI  - Does ABLA Test Performance on the ABLA Test Predict Picture Receptive Name
      Recognition with Persons with Severe Developmental Disabilities.
AB  - Research has shown that performance on the Assessment of Basic Learning Abilities
      (ABLA) test correlates with language assessments for persons with developmental
      disabilities. This study investigated whether performance on ABLA Level 6, an
      auditory-visual discrimination, predicts performance on a receptive language task
      with persons with severe developmental disabilities. Five participants who passed
      ABLA Level 6, and five who failed ABLA Level 6, were each tested on five 2-choice
      discriminations that required them to point to pictures of common objects after
      hearing their names. Four of the five participants who had failed ABLA Level 6
      failed all of the receptive name recognition tasks. All five participants who had
      passed ABLA Level 6 passed all of the name recognition tasks. The practical
      implications of these results are discussed.

PMID- 22477380
TI  - Role of contextual control in second language performance.
AB  - Transfer of training from an instructional environment to a natural environment
      may bring about ineffective language performance by bilingual individuals. In
      that regard, this study was designed to demonstrate the effect of such a
      transition on individuals' language performance. A series of Japanese and English
      words were used as sample and comparisons in a matching procedure. Differential
      conditioning was implemented in the presence two types of contextual stimuli.
      After three sets of relations were established, the physical configuration of the
      contextual stimuli was changed to more subtle appearances, and the number of
      variations in the contextual stimuli was increased. Measures of percent correct
      and response latency were used to show the negative influence on second language
      performance. Percent correct responses decreased with the subtle contextual
      stimuli for 11 out of 14 participants, and average response latency increased
      with the increased number of variations in the last phase. These findings
      indicate that the change in environmental stimuli will be a significant
      participatory factor in training of second languages.

PMID- 22477381
TI  - The veils of clio: dimensions of a behavioral narratology.
AB  - This paper outlines a behavior-analysis approach to the field of narratology, the
      study of the narrative or story, with emphasis on nonfiction stories and the
      processes by which such stories distort the world they describe. Stories are
      described in terms of (a) a behavior-analysis adaptation of Todorov's (1977)
      analysis of the plots of stories in terms of states of equilibrium/disequilibrium
      and (b) Grant's (2005) analysis of the structure of stories in terms of
      establishing operations and escape contingencies. These two sets of concepts are
      applied to understanding how and why stories lead to distortions of the events
      they report.

PMID- 22477382
TI  - The induction of naming in children with no prior tact responses as a function of
      multiple exemplar histories of instruction.
AB  - The phenomenon identified as naming is a key stage of language function that is
      missing in many children with autism and other language delay diagnoses. We
      identified four children with autism, who, prior to the implementation of this
      experiment, did not have the naming repertoire (either speaker to listener or
      listener to speaker) and who had no tact responses for two- or three-dimensional
      stimuli. Tact training alone did not result in a naming repertoire or echoic-to
      tact responses for these students. We then provided multiple exemplar instruction
      (MEI) across speaker and listener repertoires for a subset of stimuli (the
      teaching set) that resulted in untaught response components of naming and the
      capability to acquire naming after learning tacts for subsequent sets of stimuli.
      We used a delayed multiple-baseline probe design with stimuli counterbalanced
      across participants. The results showed that for all four students, mastery of
      tacts alone (the baseline or initial training condition) was not sufficient for
      the naming or echoic-to-tact repertoires to emerge. Following MEI the naming
      repertoire emerged for all four students for the initial set of stimuli. In
      addition, we tested for naming with novel stimuli that were probed prior to the
      MEI and naming also emerged following tact instruction alone for these sets. The
      results are discussed in terms of the role of naming in the incidental
      acquisition of verbal functions as part of the speaker-as-own-listener
      repertoire.

PMID- 22477383
TI  - Transferring control of the mand to the motivating operation in children with
      autism.
AB  - Few studies have made use of B. F. Skinner's (1957) behavioral analysis of
      language and precise taxonomy of verbal behavior when describing the controlling
      variables for the mand relation. Consequently, the motivating operation (MO) has
      not typically been identified as an independent variable and the nature of a
      spontaneous mand has been imprecisely described. The purpose of this study was to
      develop procedures to bring the mand response under the control of the relevant
      MO and therefore free it from the multiple controls that are more easily
      identified by practitioner's who rely on Skinner's analysis and taxonomy. Using a
      rolling time delay and prompt fade procedure both participants' mand repertoires
      were successfully transferred to the relevant MO and a listener and described
      within the context of a behavioral analysis of language.

PMID- 22477384
TI  - The Effects of a Delay of Noncontingent Reinforcement during a Pairing Procedure
      in the Development of Stimulus Control of Automatically Reinforced Vocalizations.
AB  - Children with autism and related disabilities frequently fail to develop echoic
      repertoires. Among the ways in which treatment approaches vary is the extent to
      which automatic reinforcement is utilized. The present experiment was designed to
      test the efficacy of a procedure that incorporates automatic reinforcement and
      socially mediated reinforcement in the development of an echoic repertoire. The
      implementation of this treatment package resulted in an increase in the vocal
      play and echoic behavior for two participants, each of whom had very limited
      verbal repertoires. The study was conducted as a multiple probe across sounds
      design. Vocal play for Participant 1 increased from baseline rates as low as .2
      per min to 4.5 per min during treatment, and her percent correct echoic behavior
      increased from 0% to at least 90% on both sounds. Participant 2 showed rapid
      gains in echoic control on one sound before requiring dismissal from the study.
      Interobserver agreement on the occurrence of target vocals equaled 100%. The
      results of this study have implications for which procedures to use in the
      establishment of echoic, echoic mand, and mand repertoires.

PMID- 22477385
TI  - A Comparison of Topography-based and Selection-based Verbal Behavior in Typically
      Developed Children and Developmentally Disabled Persons with Autism.
AB  - This study is a replication of Sundberg and Sundberg (1990) that compared
      topography-based verbal behavior with selection-based verbal behavior in terms of
      acquisition, accuracy, and testing for the emergence of a new verbal relation.
      Participants were three typical children and three developmentally disabled
      persons with autism. The study sought to determine which paradigm (topography
      based or selection-based) resulted in more rapid acquisition of tacts and
      intraverbals, which was associated with the fewest errors, and which paradigm
      resulted in the emergence of the highest number of new verbal relations. The
      results of the study showed that the six participants performed quite differently
      from one another. Most importantly, the results from the person with autism
      contradicted previous findings favoring selection-based verbal behavior over
      topography-based approaches for teaching verbal behavior to low-functioning
      individuals.

PMID- 22477386
TI  - A review of training intraverbal repertoires: can precision teaching help.
AB  - Intraverbal behavior is common in conversation and academic and professional
      settings. Many individuals with disabilities fail to acquire intraverbal
      repertoires. Some individuals who do acquire intraverbal behavior fail to acquire
      responses that are functional and complete. Research has examined procedures to
      establish or increase intraverbal repertoires of individuals with impaired verbal
      repertoires. Several of these studies integrate a precision teaching methodology
      with Skinner's (1957) conceptual framework. This paper reviews the literature on
      the most commonly examined methods of establishing or increasing intraverbal
      repertoires. Articles that incorporate precision teaching are emphasized. The
      review highlights the strengths (including the effectiveness) and limitations of
      each procedure. The review concludes with a discussion of the implications of
      using precision teaching to establish or increase an intraverbal repertoire and
      with suggestions for future research.

PMID- 22477387
TI  - [Significance of autopsy in patients with head and neck cancer].
AB  - BACKGROUND: Nowadays, the morphological assessment of samples obtained from
      living patients has a greater importance than the scientific knowledge which is
      gained by autopsy. Therefore, the aim of the study was a retrospective analysis
      of causes of death in patients with head and neck cancer. MATERIAL AND METHODS:
      The autopsy rate, clinical parameters of oncologic patients as well as autopsy
      findings like lethal complications, distant metastases and second primary tumors
      were retrospectively analyzed. RESULTS: From 1968 to 2007 in 91 patients with
      malignant tumors of the head and neck an autopsy was performed. In these 39 years
      an autopsy was performed in 45.9% of dead oncologic patients. Autopsy findings
      revealed distant metastases in 46.2% and second primary tumors in 17.6% of the
      patients. 49.5% of the patients died from pneumonia, 20.9% from tumor bleeding
      and 10% from progressive cachexia. CONCLUSION: The study confirms the global
      trend of a decline in autopsy numbers in the last 3 decades. However, as an
      important instrument of quality assurance autopsies continue to play an essential
      and indispensable role in medical research.

PMID- 22477388
TI  - [Persistent nasal obstruction following septoplasty: deviated nasal pyramid and
      perpendicular plate].
AB  - BACKGROUND: Functional septorhinoplasty (SRP) is a surgical procedure for
      improvement of symptomatic deformity of the inner and outer nose. Due to
      inadequate preoperative analysis and consequently insufficient surgical
      indication, septoplasty (SPL) alone may be performed. A frequent cause for
      revision septorhinoplasty (rSRP) in our institution was found to be due to a
      deviated bony pyramid in compound with a contralateral high deviation of the
      perpendicular plate, ipsilateral reluxation of the cartilaginous septum and a
      resulting nasal valve stenosis. MATERIALS AND METHODS: The medical records of all
      patients undergoing revision septorhinoplasty in our institution from 2005-2011
      were evaluated retrospectively.398 patients underwent rSRP, in 57 patients (14%)
      a deviated bony nose after septoplasty was diagnosed. In all cases a deviated
      bony nose and contralateral deviation of the perpendicular plate was found and
      corrected by rSRP. The nasal breathing was improved in all cases. This was also
      shown in an increase of endonasal volume and nasal air flow in acoustic
      rhinometry and active anterior rhinomanometry. CONCLUSION: A deviated nasal
      pyramid and perpendicular plate was found to be a common cause for persistent
      nasal obstruction after septoplasty. A careful preoperative analysis of the nose,
      the pathology of the bony and cartilaginous septum and the nasal valves is
      mandatory in order to recognize anatomical details and set up the right
      indication for rhinosurgical interventions.

PMID- 22477389
TI  - Reducing progoitrin and enriching glucoraphanin in Brassica napus seeds through
      silencing of the GSL-ALK gene family.
AB  - The hydrolytic products of glucosinolates in brassica crops are bioactive
      compounds. Some glucosinolate derivatives such as oxazolidine-2-thione from
      progoitrin in brassica oilseed meal are toxic and detrimental to animals, but
      some isothiocyanates such as sulforaphane are potent anti-carcinogens that have
      preventive effects on several human cancers. In most B. rapa, B. napus and B.
      juncea vegetables and oilseeds, there is no or only trace amount of glucoraphanin
      that is the precursor to sulforaphane. In this paper, RNA interference (RNAi) of
      the GSL-ALK gene family was used to down-regulate the expression of GSL-ALK genes
      in B. napus. The detrimental glucosinolate progoitrin was reduced by 65 %, and
      the beneficial glucosinolate glucoraphanin was increased to a relatively high
      concentration (42.6 MUmol g(-1) seed) in seeds of B. napus transgenic plants
      through silencing of the GSL-ALK gene family. Therefore, there is potential
      application of the new germplasm with reduced detrimental glucosinolates and
      increased beneficial glucosinolates for producing improved brassica vegetables.

PMID- 22477391
TI  - Low nocturnal blood pressure is associated with reduced cerebral blood flow in
      the cohort "Men born in 1914".
AB  - BACKGROUND: "Men born in 1914" is a population-based cohort study of the
      epidemiology of cardiovascular and cerebral disease. Little is known about how
      diurnal variation in blood pressure (BP) levels influence cerebral perfusion in
      very elderly populations. OBJECTIVES: To study the association between systolic
      (SBP) and diastolic BP (DBP) levels, during the day and at night, expressed
      through 24 h ambulatory BP monitoring (ABPM) and regional cerebral blood flow
      (rCBF) disturbances. METHODS: A cross-sectional study from a population-based
      cohort of 108 men 81 years of age (born in 1914) was performed in an out-patient
      university clinic. Cerebral blood flow measurements using (99m)Tc
      hexamethylpropyleneamine oxime single photon emission computed tomography and 24
      h ABPM were performed. Eleven men were excluded due to incomplete ABPM data.
      RESULTS: Mean DBP at night for each tertile was correlated to rCBF for the medial
      temporal right (P=0.012) and left (P=0.039) regions. Also, DBP during the day was
      correlated to the medial temporal right region (P=0.025). When analyses were
      stratified for DBP during the day, subjects with high DBP during the day (greater
      than 70 mmHg) showed a stronger association between low medial temporal right
      rCBF and low mean DBP at night (r=0.32, P=0.009) compared with subjects who had a
      lower daytime DBP. A corresponding positive correlation was noted for the medial
      temporal left region and daytime SBP, whereas a negative correlation was noted
      for frontal left region blood flow and SBP at night. CONCLUSIONS: A significant
      association was seen between low BP levels, especially at night, and rCBF in
      subjects with otherwise normal daytime DBP that may indicate a risk for nocturnal
      cerebral ischemia.

PMID- 22477393
TI  - The vascular component in neurogenic-arterial thoracic outlet syndrome.
AB  - The incidence of arterial compression in patients diagnosed with neurogenic
      thoracic outlet syndrome is not accurately known. In a consecutive series of 148
      patients diagnosed with neurogenic thoracic outlet syndrome, a standard objective
      method of Doppler ultrasound examination was implemented, with standard
      manoeuvres for the arm involved. These standards for assessing the incidence of
      true subclavian artery compression were previously reported. It was found that 75
      patients (51%) had definite arterial occlusion. The potential for even venous
      compression was examined in this type of patient, and 11 patients (8%) were found
      to have vascular compression of the subclavian vein when performing the
      manoeuvres. The present study is possibly the first to use a standard objective
      method to evaluate the vascular component in patients with neurogenic thoracic
      outlet syndrome.

PMID- 22477390
TI  - Risk factors for progression of calcific aortic stenosis and potential
      therapeutic targets.
AB  - Current thought regarding the progression of calcific aortic stenosis (AS) is
      presented. After summarizing contemporary ideas about AS pathogenesis, the
      present article examines the factors that may affect disease progression. Data
      indicate that this process may be accelerated by aortic valve structure, degree
      of valvular calcification, chronic renal insufficiency and cardiovascular risk
      factors such as diabetes and dyslipidemia. Finally, the present review discusses
      potential therapeutic targets to slow AS progression.

PMID- 22477392
TI  - A six-year study of diagnostic lower extremity imaging practice patterns and
      outcomes in the Veterans Affairs health care system.
AB  - BACKGROUND: The use of diagnostic imaging in the United States continues to
      increase, while investigations of the clinical implications following testing are
      lacking. The objectives of the present study are to describe the practice
      patterns and clinical outcomes that follow lower extremity diagnostic imaging.
      This is a retrospective cohort study with six years of data (1999 to 2004).
      METHODS: The sources of data for the present study were Veterans Affairs Hospital
      administrative and clinical databases. The study population included 19,209
      American veterans who had either contrast-enhanced magnetic resonance angiography
      (MRA) or digital subtraction angiography (DSA) for the assessment of peripheral
      artery occlusive disease. Descriptive statistics of the characteristics were
      provided, as well as adjusted ORs for having interventions or complications
      following an imaging procedure. RESULTS: The number of patients initially imaged
      with a contrast-enhanced MRA increased from 1999 to 2004, while those imaged with
      DSA decreased. The overall imaging rate remained relatively constant. In the
      multivariate model adjusted for the risk of complications within 30 days of the
      initial imaging procedure, the risk of complications following DSA increased 2.29
      fold (95% CI 1.60 to 3.30). More patients had an intervention following DSA (DSA
      41% versus MRA 23%, P<0.0001) but were also twice as likely to have an
      intervention with an amputation (adjusted OR 2.36, 95% CI 1.79 to 3.12).
      CONCLUSIONS: The present study illustrates the need for prospective evaluation of
      diagnostic imaging to determine how best to employ screening strategies that will
      optimize diagnostic imaging and treatment in patients diagnosed with peripheral
      artery occlusive disease.

PMID- 22477394
TI  - Intermediate term outcomes with bifurcation coronary stenting using the
      paclitaxel drug-eluting stent: a single centre experience.
AB  - BACKGROUND: Percutaneous treatment of bifurcation coronary artery disease (BCD)
      is complex and, in the era of bare metal stents (BMS), was reported to have a
      high rate of repeat target lesion revascularization (TLR). Paclitaxel drug
      eluting stents (PES) have been used in the treatment of BCD, with better overall
      outcomes than BMS. Also, acute stent thrombosis (AST), with an incidence ranging
      from 2.7% to 4.3%, has been reported with the use of bifurcation PES, and remains
      a concern in treating these patients. In the present report, intermediate term
      outcomes with BCD stenting using TAXUS Express (Boston Scientific, USA) PES are
      presented from the Genesis Medical Center. METHODS: In the present retrospective
      study, 518 consecutive de novo bifurcation stenting procedures are reported. They
      were performed in 2005 at the present institution using the TAXUS Express PES.
      Follow-up data on 312 patients (60.2%) was achieved through telephone interviews
      and reviews of medical records after a mean of 6.7 months. The primary end point
      of the present study was the combined end points of cardiac death, nonfatal
      myocardial infarction (MI) and TLR. Secondary outcomes included the individual
      end points of death, cardiac death, AST, target vessel revascularization (TVR),
      TLR, ST elevation MI and non-ST elevation MI on intermediate term follow-up.
      RESULTS: The mean (+/- SD) age of the patients was 66+/-12 years. Acute
      procedural success was 95% (main branch, 99%; side branch, 95.9%). The following
      intermediate term outcomes with bifurcation drug-eluting stents were: TLR, 6.7%;
      TVR, 12.2%; definite and probable AST, 1.6%; death, 6.7%; cardiac death, 2.9%;
      non-ST elevation MI, 0.7%; ST elevation MI, 2.0%; and the combined primary end
      point, 9.9%. The outcomes for patients who underwent main branch stenting were
      not statistically different from those with bifurcation stenting, with an overall
      combined end point favouring main branch stenting alone (5.8% versus 10.8%, P not
      significant). CONCLUSION: The TAXUS Express PES carry acceptable intermediate
      term outcomes in the treatment of BCD compared with historic controls with BMS,
      with low TLR, TVR and overall primary combined end point. Main branch stenting
      alone is safe, with a trend toward fewer adverse events than bifurcation
      stenting.

PMID- 22477395
TI  - An update on the 'fast-track' abdominal aortic aneurysm repair.
AB  - Patients who have unfavourable anatomy for endovascular repair of an abdominal
      aortic aneurysm require open repair. This is particularly the case for juxtarenal
      aortic aneurysms, or those patients with small or occluded iliac access
      vessels.An experience of 'fast-track' abdominal aortic aneurysm repair that was
      previously reported is updated in the present case. A retroperitoneal approach to
      the aorta is taken, using a small incision, and is followed by a patient care
      pathway protocol that demonstrated excellent results and a shortened length of
      stay. The present update on 56 patients is approximately double the previously
      reported experience.

PMID- 22477396
TI  - Acquired aneurysm of the left sinus of Valsalva and coexistence of coronary
      artery disease with hypereosinophilia in a young menstruating woman: a case
      report.
AB  - A 35-year-old menstruating woman presented with exertional angina, and was
      diagnosed with an unruptured left sinus of Valsalva and a noncoronary sinus of
      Valsalva aneurysm. Hypereosinophilia and coronary artery occlusion was also
      observed; this association is extremely rare.

PMID- 22477397
TI  - Iliocrural long bypass using the deep femoral artery as a midway outflow for limb
      salvage: report of a case.
AB  - A patient who presented with total occlusion of the right common femoral artery,
      superficial femoral artery and popliteal artery is reported. Ilio-deep femoral
      and deep femoroposterior tibial bypass with an expanded polytetrafluoroethylene
      graft and an in situ saphenous vein graft, respectively, was successfully
      performed. A simple and reproducible technique for crural bypass in patients
      whose common and superficial femoral arteries are unavailable as inflow and
      outflow sites is presented.

PMID- 22477398
TI  - A modern cause of an old disease. Constrictive pericarditis after percutaneous
      coronary intervention: a case report.
AB  - A 70-year-old patient developed severe constrictive pericarditis with exertional
      dyspnea, lethargy and marked peripheral edema four months after percutaneous
      coronary intervention for acute coronary syndrome. The diagnosis of constrictive
      pericarditis was confirmed by cardiac catheterization and computed tomography.
      Despite the short duration of the disease, the pericardium showed fibrosis and
      had a thickness of approximately 6 mm. The patient underwent pericardiectomy,
      with a satisfactory outcome. Hemopericardium due to coronary microperforation was
      suspected to be responsible for the development of constrictive pericarditis.
      This unusual mid-term complication of percutaneous coronary intervention has
      rarely been reported and should be suspected in this particular clinical setting.

PMID- 22477399
TI  - Klippel-Feil syndrome and supra-aortic arch anomaly: a case report.
AB  - Patients with Klippel-Feil syndrome have an increased incidence of supra-aortic
      arch anomalies. The present report presents the case of a patient who, during
      evaluation of his carotid arteries for nonspecific symptoms, was found to have an
      anomaly of the supra-aortic branches and Klippel-Feil syndrome.

PMID- 22477400
TI  - Teaching Manual Signs to Adults With Mental Retardation Using Matching-to-Sample
      Procedures and Stimulus Equivalence.
AB  - The objective of this study was to teach manual signs through an automated
      matching-to-sample procedure and to test for the emergence of new conditional
      relations and imitative behaviors. Seven adults with mild to severe mental
      retardation participated. Four were also hearing impaired. Relations between
      manual signs (set A) and pictures (set B) were initially taught, followed by the
      training of corresponding printed words (set C) and pictures (set B). Further
      presentations of conditional discriminations tested for the emergence of AC,
      followed by tests for the emergence of imitative signing behavior (D) in the
      presence of either pictures (B) or printed words (C). Each stimulus set was
      comprised of 9 elements. The stimuli were still pictures, printed words, and
      dynamic presentations of manual signs. A pretest was conducted to determine which
      signs the participants could make pre-experimentally. Teaching was arranged in a
      multiple baseline design across 3 groups of 3 words each. The purpose of the
      present study was to determine whether participants would emit manual signs in
      expressive signs tests as a result of observation (video modeling) during match
      to-sample training in the absence of explicit training. Five of the 7 subjects
      passed tests of emergence and emitted at least 50% of the signs. Two were hearing
      impaired with signing experience, and 3 were not hearing impaired and had no
      signing experience. Thus, observation of video recorded manual signs in a
      matching-to-sample training procedure was effective at establishing some signs by
      adults with mental retardation.

PMID- 22477401
TI  - Investigating the acquisition, generalization, and emergence of untrained verbal
      operants for mands acquired using the picture exchange communication system in
      adults with severe developmental disabilities.
AB  - This study compared the total amount of training time and total number of trial
      blocks for individuals with severe developmental disabilities to acquire mands
      under control of unconditioned establishing operations and mands under control of
      transitive conditioned establishing operations for manual sign and for the
      Picture Exchange Communication System (PECS). Also examined was the
      generalization of mands across settings and communicative partners, as well as
      the emergence of untrained tacts and intraverbals for mands acquired using PECS.
      Mands for preferred items and for items needed to complete a chained task were
      acquired more rapidly and in fewer training blocks for PECS than for manual sign.
      Moreover, mands established using PECS generalized across settings and
      communicative partners. Finally, untrained tacts and intraverbals using PECS were
      shown to emerge for some of the participants following PECS training. These
      results suggest that PECS may be a viable alternative communication system for
      adults with severe developmental disabilities who have little or no history of
      systematic instruction and limited imitative repertoires.

PMID- 22477402
TI  - A behavior analytic analogue of learning to use synonyms, syntax, and parts of
      speech.
AB  - Matching-to-sample and sequence training procedures were used to develop
      responding to stimulus classes that were considered analogous to 3 aspects of
      verbal behavior: identifying synonyms and parts of speech, and using syntax.
      Matching-to-sample procedures were used to train 12 paired associates from among
      24 stimuli. These pairs were analogous to synonyms. Then, sequence
      characteristics were trained to 6 of the stimuli. The result was the formation of
      3 classes of 4 stimuli, with the classes controlling a sequence response
      analogous to a simple ordering syntax: first, second, and third. Matching-to
      sample procedures were then used to add 4 stimuli to each class. These stimuli,
      without explicit sequence training, also began to control the same sequence
      responding as the other members of their class. Thus, three 8-member functionally
      equivalent sequence classes were formed. These classes were considered to be
      analogous to parts of speech. Further testing revealed three 8-member equivalence
      classes and 512 different sequences of first, second, and third. The study
      indicated that behavior analytic procedures may be used to produce some
      generative aspects of verbal behavior related to simple syntax and semantics.

PMID- 22477403
TI  - The effects of praising qualifying autoclitics on the frequency of reading.
AB  - In the current study, tacts with positive qualifying autoclitics for reading were
      reinforced in order to determine if this procedure would increase the time spent
      reading by participants. Participants included 5 children, between 9-10 years
      old. Participants were individually exposed to 4 free operant sessions during
      which they were instructed to independently choose play activities. During pre-
      and post-treatment conditions, no consequences were provided for choosing
      reading. In addition, 4 treatment sessions were conducted on days separate from
      the free operant session days, during which the experimenter praised each
      positive reading-related statement emitted by the participant. Following
      treatment sessions, 4 out of 5 participants increased the time allocated to
      reading, suggesting that reading could be increased when praise is delivered
      contingent upon positive reading-related verbalizations.

PMID- 22477404
TI  - A functional analysis of non-vocal verbal behavior of a young child with autism.
AB  - The functions of an American Sign Language response were experimentally evaluated
      with a young boy diagnosed with autism. A functional analysis procedure based on
      that reported by Lerman et al. (2005) was used to evaluate whether the target
      sign response would occur under mand, tact, mimetic, or control conditions. The
      target sign was observed most often in the mand and mimetic test conditions, very
      seldom in the tact test condition, and never in the control condition. These
      results support those reported by Lerman et al. and extend previous research by
      evaluating a non-vocal verbal response using a brief multi-element arrangement
      with a single control condition. The implications for language assessment and
      suggestions for future research are discussed.

PMID- 22477405
TI  - Discrete Trial Instruction vs. Mand Training for Teaching Children With Autism to
      Make Requests.
AB  - The present study compared the effects of discrete trial instruction (DTI) and
      mand training on the acquisition of independent requests in 6 children with
      autism. Two multiple-probe designs across participants were conducted with 3
      participants receiving mand training followed by DTI and the other 3 receiving
      DTI followed by mand training. Eye contact and challenging behaviors were also
      assessed across conditions. Results indicate that 5 of 6 participants made more
      independent requests and acquired requesting faster in the mand training
      condition, had slightly better eye contact in the DTI condition, and fewer
      challenging behaviors in the mand training condition. Overall, the results
      indicate that mand training is a more efficient method for teaching children with
      autism to make requests.

PMID- 22477406
TI  - Assessing transfer of stimulus control procedures across learners with autism.
AB  - The purpose of this study was to evaluate the effectiveness of 2 transfer of
      stimulus control procedures to teach tacting to individuals with autism. Five
      participants with differing verbal skills were assessed by a subset of the ABLLS
      prior to intervention, then were taught 36 previously unknown tacts using the
      receptive-echoic-tact (r-e-t) and echoic-tact (e-t) transfer procedures. Each
      transfer method was used separately to establish different tacts, in a multiple
      baseline design across tacts for 3 sets of stimuli. The results showed that 4 out
      of 5 participants (who demonstrated mands, tacts, echoics, and sometimes
      intraverbals prior to the study) acquired all targeted tacts when either r-e-t or
      e-t training was presented. One participant (who emitted no verbal operants at
      the onset of the study) did not acquire any tacts. While some participants
      appeared to learn more quickly with one transfer method, neither method emerged
      as more efficient with learners with fewer or more extensive verbal skills. The
      results indicate that both transfer methods promoted the acquisition of tacts for
      learners with autism with at least minimal verbal skills.

PMID- 22477407
TI  - How kids learn to say the darnedest things: the effect of multiple exemplar
      instruction on the emergence of novel verb usage.
AB  - We report experiments using time-lagged pre- and postintervention designs with
      (a) 4 first graders with learning delays, and (b) a systematic replication with 3
      preschoolers with learning delays. Both experiments tested the effects of
      multiple exemplar instructional procedures (MEI) on the emergence of untaught
      past tense emission of novel regular verbs (e.g., jumped derived from jump) and
      grammatically inaccurate but experimentally correct usage of irregular verbs
      (e.g., singed derived from sing). Prior to the MEI, none of the children could
      produce regular or irregular past tense forms to pictures that provided simulated
      contexts (pictures with backgrounds for past and present tense). MEI provided
      across the picture contexts for past and present tense used separate training
      sets of verbs to teach children to form regular past tense. After either 1 or 2
      MEI training sets, the children emitted accurate past tense forms of the untaught
      regular and inaccurate, but experimentally correct irregular verbs. These
      findings provided an instructional history that resulted in the children's
      acquisition of past tense for untaught regular past tense verbs and "creative"
      errors with irregular tenses. Results are discussed in terms of the research on
      experimentally induced sources for novel verbal behavior and related
      interpretations.

PMID- 22477408
TI  - A comparison of stimulus-stimulus pairing, standard echoic training, and control
      procedures on the vocal behavior of children with autism.
AB  - An alternating treatments design was employed to compare the effect of stimulus
      stimulus pairing, standard echoic training, and a control condition on the vocal
      behavior of 3 preschoolers with autism. Data were recorded during pre- and
      postsession observations. During the stimulus-stimulus pairing condition, the
      experimenter's vocal model was paired with the delivery of a preferred item.
      During the standard echoic training condition, the experimenter presented a vocal
      model and delivered a preferred item contingent on an echoic response. During the
      control condition, the experimenter presented a vocal model and, after a 10-s
      delay, presented a preferred edible item. Results from the post-session
      observations during the stimulus-stimulus pairing condition showed an immediate
      but temporary increase in the target sound for 1 participant only. Implications
      and suggestions for future research are provided.

PMID- 22477409
TI  - Using stimulus-stimulus pairing and direct reinforcement to teach vocal verbal
      behavior to young children with autism.
AB  - In this study the effect of a stimulus-stimulus pairing procedure was used as
      part of a clinical investigation to increase vocalizations for two young children
      diagnosed with autism. This procedure involved pairing a vocal sound with a
      preferred stimulus (e.g., toy) to condition automatic reinforcement. In addition,
      this study assessed the effects of a direct reinforcement procedure to bring a
      vocalization under echoic control following the pairing procedure for 1 of the
      participants. The results showed the pairing procedure was used successfully to
      increase a vocalization for one of the participants, and the vocalization was
      brought under echoic control.

PMID- 22477410
TI  - A behavioral conceptualization of aphasia.
AB  - Aphasia is an acquired language impairment that affects over 1 million
      individuals, the majority of whom are over age 65 (Groher, 1989). This disorder
      has typically been conceptualized within a cognitive neuroscience framework, but
      a behavioral interpretation of aphasia is also possible. Skinner's (1957)
      analysis of verbal behavior proposes a framework of verbal operants that can be
      integrated with the work of Sidman (1971) and Haughton (1980) to describe the
      language difficulties individuals with aphasia experience. Using this synthesis
      of models, we propose a new taxonomy of aphasia based on the observed deficit
      relations. Assessment and treatment implications are also discussed.

PMID- 22477411
TI  - Conditional discrimination in the intraverbal relation: a review and
      recommendations for future research.
AB  - Conditional discrimination is inherent in the intraverbal relation when one
      verbal stimulus alters the evocative effect of another verbal stimulus and they
      collectively evoke an intraverbal response. Rarely in research on conditional
      discriminations have both conditional and discriminative stimuli been vocal
      verbal and rarely have the responses been topography-based. Making conditional
      discriminations in intraverbal behavior is a repertoire that is often delayed in
      children with autism and other developmental disabilities. Reviewed in this paper
      is research on teaching intraverbal behavior, auditory conditional
      discriminations, and restricted stimulus control. The purpose of these reviews is
      to identify the extent to which previous researchers examined conditional
      discriminations in the intraverbal relation and to recommend directions for
      research in this area.

PMID- 22477413
TI  - Knee-length graduated compression stockings for thromboprophylaxis in air
      travellers: A meta-analysis.
AB  - OBJECTIVE: To systematically review the randomized controlled trials that have
      evaluated the efficacy of knee-length (KL) compression stockings for
      thromboprophylaxis in air travellers. METHOD: After an electronic database
      search, the randomized controlled trials that studied passengers on long-haul
      flights were selected and analyzed to generate summative data. RESULTS: Nine
      trials studying participants using KL stockings were analyzed. Forty-six of 1261
      participants randomly assigned to the control group developed deep vein
      thrombosis (DVT), compared with two of 1237 participants (0.16%) in the KL
      stockings group. The weighted risk difference was -0.034, which indicated that
      the absolute difference was 3.4% in the incidence of DVT, in favour of KL
      stockings. The number needed to treat with KL stockings to avoid one case of DVT
      was 29.4. However, there was significant heterogeneity among trials. The RR for
      DVT was 0.08 in high-risk participants and 0.14 in low- to medium-risk
      participants. CONCLUSION: KL stockings are effective for thromboprophylaxis in
      air travellers at low, medium and high risk of DVT. The use of KL stockings
      should form an important part of air traveller education on lowering the burden
      of DVT. The results of the present meta-analysis can be used to advise travellers
      on their risk of DVT and preventive strategies.

PMID- 22477414
TI  - Efficacy and safety of a single 2 mg dose or 4 mg double dose of alteplase for 50
      occluded chest ports using a unique instillation technique.
AB  - PURPOSE: To evaluate the effectiveness and safety of a single 2 mg dose or a 4 mg
      double dose of alteplase for restoring function in occluded chest ports. METHODS:
      A prospective, open-label, nonblinded study was performed on 40 enrolled patients
      with a total of 50 chest ports at the Henry Ford Hospital Interventional
      Radiology Department (Detroid, Michigan, USA). Alteplase (Cathflo Activase;
      Genentech, USA), a recombinant tissue plasminogen activator produced by
      recombinant DNA technology, was used to restore the function of 50 occluded chest
      ports. Occlusion was defined as the inability to withdraw blood freely from the
      port, or the inability to flush the port easily. A 2 mg (2 mL) dose of alteplase
      was injected into the port through a Huber needle, using a gentle push and pull
      technique, and was left to dwell for 30 min. If the port remained occluded after
      the initial 2 mg alteplase treatment, an additional 2 mg alteplase treatment was
      administered with the same dwell time of 30 min. If a port had remained occluded
      despite the above regimen, this outcome would have been considered a failure and
      the chest port would have required surgical intervention. However, all ports were
      successfully treated, and no surgical intervention was required. The safety end
      points included minor or major hemorrhages, such as intracranial hemorrhages, or
      sepsis. Safety end points were determined by a 24 h follow-up telephone call.
      RESULTS: Of the 50 chest ports (30 single ports and 10 double ports) treated with
      alteplase, 36 required 2 mg (72%) and 14 required 4 mg (28%). The efficacy end
      point was 100% for all chest ports treated, without any adverse events.
      CONCLUSION: High efficacy and safety rates of restoring function in occluded
      chest ports were obtained with 2 mg or 4 mg doses of alteplase. Part of this high
      efficacy rate may be due to the gentle push and pull technique used in the
      present study.

PMID- 22477415
TI  - Three-dimensional aortic aneurysm model and endovascular repair: an educational
      tool for surgical trainees.
AB  - OBJECTIVES: Endovascular aortic aneurysm repair (EVAR) is a current valid
      treatment option for patients with abdominal aortic aneurysms (AAAs). The success
      of EVAR depends on the selection of appropriate patients, which requires detailed
      knowledge of the patient's vascular anatomy and preoperative planning. Three
      dimensional (3D) models of AAA using a rapid prototyping technique were developed
      to help surgical trainees learn how to plan for EVAR more effectively. METHOD:
      Four cases of AAA were used as prototypes for the models. Nine questions
      associated with preoperative planning for EVAR were developed by a group of
      experts in the field of endovascular surgery. Forty-three postgraduate trainees
      in general surgery participated in the present study. The participants were
      randomly assigned into two groups. The 'intervention' group was provided with the
      rapid prototyping AAA models along with 3D computed tomography (CT) corresponding
      to the cases of the test, while the control group was provided with 3D CTs only.
      RESULTS: Differences in the scores between the groups were tested using the
      unpaired t test. The mean test scores were consistently and significantly higher
      in the 3D CT group with models compared with the 3D CT group without models for
      all four cases. Age, year of training, sex and previous EVAR experience had no
      effect on the scores. CONCLUSION: The 3D aortic aneurysm model constructed using
      the rapid prototype technique may significantly improve the ability of trainees
      to properly plan for EVAR.

PMID- 22477416
TI  - Can patients with significant renal artery stenosis who underwent renal
      angioplasty be monitored postprocedure in the general ward instead of the high
      dependency unit?
AB  - INTRODUCTION: Renal angioplasty has been increasingly used to treat significant
      renal artery stenosis (RAS). At the Tan Tock Seng Hospital (Singapore), renal
      angioplasty patients are routinely admitted to the high dependency unit (HDU)
      postprocedure for monitoring. METHODS: The complications of the RAS patients were
      reviewed postangioplasty, and it was determined whether the patients could be
      monitored in the general ward (GW) instead of the HDU. Cases of patients with RAS
      of more than 50% who underwent angioplasty between January 1999 and September
      2006 were reviewed retrospectively. RESULTS: There were 35 patients with
      significant RAS who underwent angioplasty. Thirty were monitored in the HDU. Five
      were monitored in the GW because there were no HDU beds available. Patients in
      the GW were monitored every 30 min for 6 h, then every hour for 24 h. No
      immediate complications or deaths were recorded in the present series.
      CONCLUSION: It may be safe and cost-effective to monitor patients with
      significant RAS postangioplasty in the GW.

PMID- 22477417
TI  - Supervised and home-based exercise training for patients with intermittent
      claudication.
AB  - Home-based exercise training, applied as the primary treatment in patients with
      intermittent claudication, has produced inconsistent effects on walking capacity
      in previous published studies. The aim of the present study was to evaluate
      whether a home-based exercise training program could maintain improved walking
      capacity and other functional variables achieved through a supervised exercise
      training program. The present design was a 48-week self-controlled study. The
      first 12-week period was a control stage in which no prescribed exercise program
      was provided, the second 12-week period was a supervised treadmill-walking
      training program and the following 24-week period was a home-based exercise
      program. Twenty-two subjects with intermittent claudication were recruited
      initially; 15 of them (14 men and one woman) completed the whole program. Walking
      capacity, peak oxygen uptake, walking economy and ankle-brachial index were
      measured at baseline and at 12, 24 and 48 weeks. There was no significant change
      in the measured variables after the control stage. The 12-week supervised
      treadmill-walking training program significantly increased pain-free walking
      time, maximal walking time and peak oxygen uptake. Walking economy was also
      significantly improved. These improvements were successfully maintained after 24
      weeks of home-based training. The results indicated that 12 weeks of supervised
      treadmill-walking training followed by a home-based training program is an
      effective model of exercise rehabilitation for patients with intermittent
      claudication.

PMID- 22477418
TI  - Prevalence of risk factors and of coronary artery disease, ischemic stroke,
      carotid arterial disease and lower extremity peripheral arterial disease in 96
      patients undergoing elective surgery for an abdominal aortic aneurysm.
AB  - Ninety-six patients (77 men and 19 women), with a mean (+/- SD) age of 77+/-9
      years, underwent elective surgery between 2006 and 2007 for an abdominal aortic
      aneurysm (AAA) greater than 5.5 cm in diameter. Of the 96 patients with an AAA,
      31 (32%) were smokers, 85 (89%) had hypertension, 78 (81%) were treated with
      statins for hypercholesterolemia and 24 (25%) had diabetes mellitus. As well, 71
      (74%) had coronary artery disease, 17 (18%) had a previous ischemic stroke, 19
      (20%) had carotid arterial disease and 37 (39%) had peripheral arterial disease
      of the lower extremities.

PMID- 22477419
TI  - Five-year treatment of chronic venous insufficiency with O-(beta-hydroxyethyl)
      rutosides: safety aspects.
AB  - Chronic venous insufficiency (CVI), and related signs and symptoms of venous and
      diabetic microangiopathy, can be effectively treated with O-(beta-hydroxyethyl)
      rutosides (HR). The aim of the present independent registry study was to evaluate
      HR in a long-term (five-year) period of administration that examined the
      tolerability and safety of HR. Patients with severe CVI and venous
      microangiopathy were included in the registry. Subjects who completed five years
      of treatment were considered in the analysis. Blood parameters, liver and renal
      function tests, microalbuminuria (in diabetic patients) and cholesterol levels
      were evaluated to assess the effects of HR treatment. Four groups were studied -
      group A (98 patients) received oral HR (1500 mg per day), group B (87 diabetic
      patients with CVI) was treated with 2 g of HR per day, group C (90 controls,
      including 42 diabetic patients) had no pharmacological treatment and group D (113
      patients, including 48 diabetic patients) used elastic stockings. No significant
      negative changes in blood parameters were recorded at two and five years.
      Decreases in microalbuminuria and total cholesterol, and an increase in high
      density lipoprotein cholesterol were observed in HR-treated patients,
      particularly in diabetic patients. Minimal (nonsignificant) variations were
      observed in the groups that did not use HR. In conclusion, HR treatment is safe,
      and some positive effects from HR on cholesterol levels and microalbuminuria (in
      diabetic patients) that were previously observed may suggest potential new
      clinical applications.

PMID- 22477420
TI  - Custodiol versus Plegisol: A phase 3 multicentre myocardial protection study.
AB  - BACKGROUND: While considered simple and effective, crystalloid antegrade
      cardioplegia solutions have had few prospective multicentre comparison trials.
      METHODS: A commercial intracellular-type histidine-tryptophan-ketoglutarate (HTK)
      cardioplegia solution (Custodiol HTK; Kohler Chemie GmbH, Germany) designed for 4
      h of protection after a single administration was compared with a standard
      extracellular multidose product (Plegisol [PL]; Hospira Inc, USA) in an open
      label, randomized, prospective seven-institution trial. A total of 136 isolated
      coronary bypass patients were randomly assigned into two groups and stratified by
      ejection fraction into categories of 40% or greater (n=118) and 20% to 39%
      (n=18). RESULTS: The mean age of the study cohort was 62 years, of which 94% were
      men. Seventy per cent of patients had Canadian Cardiovascular Society class III
      angina and 75% had three-vessel disease anatomy. Cross-clamp times were nearly
      identical for patients in both cardioplegia groups; however, defibrillation was
      needed less often for patients who were treated with HTK (64% versus 91%,
      P<0.01). Hospital and intensive care unit stays, creatine kinase isoenzyme MB
      curves, cardiac outputs, inotrope levels, and deaths or serious adverse events
      (PL=13, HTK=14) were very similar between groups. Logistic regression showed that
      myocardial infarction or possible treatment-related adverse events were
      associated with high cardiac troponin I (cTn-I) levels 6 h after the procedure
      (P=0.001), and HTK treatment (OR 3.5, P=0.01). The primary study end point (6 h
      post-ischemia cTn-I) favoured PL (16.7+/-13.2 MUg/L versus 20.3+/-13.5 MUg/L,
      P=0.01). Patients who underwent circumflex grafting had higher cTn-I levels with
      HTK (P<0.001) and 48% required reinfusions due to cardiac warming. Longer
      intervals between doses correlated with high cTn-I levels (P=0.02). HTK provided
      prolonged protection with low cTn-I release (10 MUg/L or less), although this
      occurred less frequently than with PL (17 versus 27 patients, P=0.06).
      CONCLUSIONS: HTK caused more structural protein release and adverse events than
      PL, even when reinfusion was implemented.

PMID- 22477421
TI  - A case report on asymptomatic ascending aortic dissection.
AB  - Aortic dissection is a relatively rare but dreadful illness, often presenting
      with tearing chest pain and acute hemodynamic compromise. Early and accurate
      diagnosis and treatment are essential for survival. In the present review, a rare
      case of an asymptomatic ascending aortic dissection is reported. The general
      clinical manifestations, diagnosis and management of aortic dissection will also
      be reviewed.

PMID- 22477422
TI  - Paraganglioma neck - a neuroendocrine tumour revisited.
AB  - Paragangliomas are uncommon neck swellings, usually associated with hypertension
      and flushing. They occur in the neck and other amine precursor uptake and
      decarboxylation cell rests, and are a challenge to the anesthetist at the time of
      excision.

PMID- 22477424
TI  - The verbal behavior approach.

PMID- 22477423
TI  - Subclavian steal and rest pain in a case of brachiocephalic artery occlusion.
AB  - A patient with multiple vessel disease presented with symptoms of significant
      bilateral upper extremity pain and weakness that was more significant on the
      right side. On carotid duplex scanning, brachiocephalic artery occlusion with
      retrograde flow was noted through the right common carotid and right vertebral
      arteries at rest. Furthermore, 50% to 90% occlusion of the left internal carotid
      was noted. Filling of the right subclavian artery was noted to be through the
      right vertebral and right common carotid arteries. Unlike isolated subclavian
      steal syndrome, brachiocephalic artery occlusion induces significant hemodynamic
      alterations in extracranial arterial flow, which normally produces no symptoms at
      rest, but may produce symptoms with exercise. The occurrence of subclavian steal
      phenomenon in the presence of brachiocephalic occlusion is extremely rare. The
      present case is the first to report a patient presenting with bilateral upper
      extremity rest pain in the presence of brachiocephalic artery occlusive disease.

PMID- 22477425
TI  - Equivalence relations and behavior: an introductory tutorial.
AB  - With an emphasis on procedural fundamentals, the original behavior-analytic
      equivalence experiments and the equivalence paradigm are described briefly. A few
      of the subsequent developments and implications are noted, with special reference
      to the possible significance of the findings with respect to language and
      cognition.

PMID- 22477426
TI  - Extending the assessment of functions of vocalizations in children with limited
      verbal repertoires.
AB  - The current study examined the effectiveness of an experimental functional
      analysis for assessing the functions of emergent vocal-verbal behavior in
      children with developmental disabilities. Experiment 1 consisted of a systematic
      replication of Lerman et al. (2005). Participants were 3 children with
      developmental disabilities, between the ages of 2 and 5 years, with limited vocal
      verbal repertoires, who could emit at least two clear vocalizations. Results
      indicated that for all participants, targeted vocalizations functioned as mands,
      tacts, or both. The purpose of Experiment 2 was to address some of the
      limitations of Experiment 1 while using a different experimental design. Results
      of Experiment 2 suggested that participants' targeted vocalizations served as
      tacts, echoics, or both. Results are discussed in terms of the utility of this
      methodology for the selection and development of effective language interventions
      as well as implications for our current knowledge of verbal behavior.

PMID- 22477427
TI  - General outcome measures for verbal operants.
AB  - A general outcome measure (GOM) can be used to show progress towards a long-term
      goal. GOMs should sample domains of behavior across ages, be sensitive to change
      over time, be inexpensive and easy to use, and facilitate decision making.
      Skinner's (1957) analysis of verbal behavior may benefit from the development of
      GOM. To develop GOM, we conducted a review of the literature on mands, tacts,
      echoics, and intraverbals. The four areas reviewed included (a) an examination of
      the participant's response form (i.e., vocal or nonvocal), (b) the type of prompt
      used, (c) types of materials used, and (d) timing of responses or sessions. Based
      on the review of the literature, we developed GOM for mands and tacts. This paper
      attempts to bridge the concept of GOMs with Skinner's analysis of verbal
      behavior.

PMID- 22477428
TI  - The "silent dog" method: analyzing the impact of self-generated rules when
      teaching different computer chains to boys with autism.
AB  - The purpose of the study was to extend the literature on verbal self-regulation
      by using the "silent dog" method to evaluate the role of verbal regulation over
      nonverbal behavior in 2 individuals with autism. Participants were required to
      talk-aloud while performing functional computer tasks.Then the effects of
      distracters with increasing demands on target behavior were evaluated as well as
      whether self-talk emitted by Participant 1 could be used to alter Participant 2's
      performance. Results suggest that participants' tasks seemed to be under control
      of self-instructions, and the rules generated from Participants 1's self-talk
      were effective in teaching computer skills to Participant 2. The silent dog
      method was useful in evaluating the possible role of self-generated rules in
      teaching computer skills to participants with autism.

PMID- 22477429
TI  - Is a reasonable attempt reasonable? Shaping versus reinforcing verbal attempts of
      preschoolers with autism.
AB  - The effectiveness of a language-training procedure that emphasized reinforcing
      vocal "reasonable attempts" (any response directed at an interventionist and
      within a broader class of correct responses) was compared with a procedure that
      emphasized shaping (reinforcing successive approximations that more closely
      resembled the target vocalization). Three preschoolers who had been diagnosed
      with autism spectrum disorders participated in the study. Data indicated that the
      children mastered vocal skills more rapidly when they learned through shaping
      than in the reasonable attempts condition. Implications for teaching children
      with autism spectrum disorders are discussed.

PMID- 22477430
TI  - Increasing vocal variability in children with autism using a lag schedule of
      reinforcement.
AB  - Variability has been demonstrated to be an operant dimension of behavior
      (Neuringer, 2002; Page & Neuringer, 1985). Recently, lag schedules have been used
      to demonstrate operant variability of verbal behavior in persons with a diagnosis
      of autism (e.g., Lee, McComas, & Jawor, 2002). The current study evaluated the
      effects of a Lag 1 schedule on the vocal variability of 2 nonverbal children with
      a diagnosis of autism. Results showed systematic increases in variability during
      the Lag 1 schedule. Implications of lag schedules for speech and language
      training are discussed.

PMID- 22477431
TI  - Teaching intraverbal behavior to children with autism: a comparison of textual
      and echoic prompts.
AB  - Although echoic prompts may be effective for teaching intraverbal behavior to
      children with autism, the performance of some children may become dependent on
      such prompts (i.e., the prompts cannot be eliminated). Recent research suggests
      that visual rather than echoic prompts may be used to teach children with autism
      a variety of skills and may facilitate independent performance. In the present
      study, an adapted alternating treatments design was used to compare the effects
      of using visual (textual) and echoic prompts on acquisition of intraverbal
      responses (answering questions) by 2 children with autism. The results indicated
      that the textual prompts were more effective than the echoic prompts.
      Implications for the use of visual prompts during instruction with children with
      autism are discussed.

PMID- 22477432
TI  - Relational frame theory: an overview of the controversy.
AB  - Although Skinner's Verbal Behavior (1957) was published over 50 years ago,
      behavior-analytic research on human language and cognition has been slow to
      develop. In recent years, a new behavioral approach to language known as
      relational frame theory (RFT) has generated considerable attention, research, and
      debate. The controversy surrounding RFT can be difficult to fully appreciate,
      partly because of the complexity of the theory itself and partly because the
      debate has spanned several years and several journals. The current paper aims to
      provide a concise overview of RFT and a summary of key points of debate and
      controversy.

PMID- 22477433
TI  - The Hefferline Notes: B. F. Skinner's First Public Exposition of His Analysis of
      Verbal Behavior.
AB  - B. F. Skinner's first public exposition of his analysis of verbal behavior was
      the Hefferline Notes (1947a), a written summary of a course Skinner taught at
      Columbia University during the summer of 1947 just prior to his presentation of
      the William James Lectures at Harvard University in the fall. The Notes are
      significant because they display Skinner's analysis as it made the transition
      from spoken to written form; moreover, they are an effective supplemental source
      of examples and early approximations for comprehending Skinner's functional
      verbal operants.

PMID- 22477434
TI  - A quarter century of the analysis of verbal behavior: an analysis of impact.
AB  - The Analysis of Verbal Behavior (TAVB) has been published since 1982, and during
      this time, interest in verbal behavior research appears to have increased
      substantially within behavior analysis. The purpose of the present analysis was
      to assess the influence of TAVB on the field by (a) counting citations of TAVB
      articles in the Journal of the Experimental Analysis of Behavior (JEAB) and the
      Journal of Applied Behavior Analysis (JABA) from 1983 through 2007, (b) examining
      which other journals cite TAVB, and (c) calculating impact-factor estimates for
      2003 through 2007. Citations of TAVB articles began to appear in JEAB and JABA in
      the late 1980s to early 1990s, and by the end of 2007, almost a third of all
      articles published in TAVB had been cited in either JEAB or JABA. Other journals
      that cite TAVB include The Behavior Analyst and The Psychological Record. The
      estimated impact factor ranged from 0.267 to 0.600. Strategies for increasing the
      impact of TAVB are discussed.

PMID- 22477435
TI  - Publication trends in the analysis of verbal behavior: 1999-2008.
AB  - The Analysis of Verbal Behavior (TAVB) publishes experimental and theoretical
      papers relevant to a behavioral analysis of language. Normand, Fossa, and Poling
      (2000) reviewed the published studies in TAVB across several dimensions and found
      that despite the growth of the journal, most articles published in TAVB from 1982
      to 1998 were nonexperimental. The current study extends this review by analyzing
      articles published in TAVB from 1999 through 2008. Results showed that 48% of the
      articles published between 1999 and 2008 were experimental (65% in the last 4
      years), 93% of them used within-subject experimental designs, and most of them
      (54%) included children with developmental disabilities. This suggests an
      increased interest in the experimental analysis of verbal behavior with a focus
      on teaching language to individuals with disabilities.

PMID- 22477436
TI  - Validity and reliability of a radio positioning system for tracking athletes in
      indoor and outdoor team sports.
AB  - Radio-frequency local positioning systems (LPS) have the potential to provide
      accurate location information about sport players for performance analysis,
      making available for study the emergent nature of interpersonal coordination and
      collective decision-making behaviour among players in both indoor and outdoor
      sports. However, no available publications have validated the performance of LPS
      for indoor sports. The objective of this study was to validate the performance of
      an LPS in an indoor venue and to compare it to performance observed in an outdoor
      venue using static and dynamic measurements. Our results showed that the absolute
      positioning errors obtained from the static measurements of the LPS were
      comparable for both indoor and outdoor venues, with mean errors of 12.1 cm
      outdoors and 11.9 cm indoors. From the dynamic measurements, we analysed the
      relative position error and the distance estimation performance of the system.
      The 90th-percentile relative position errors were 28 cm for the indoor venue
      versus 18 cm for the outdoor venue. On average, the LPS overestimated the
      distance travelled, and the performance was similar for both indoor and outdoor
      venues. On a linear course, the mean errors of the distance estimates were 2.2%
      of the total distance indoors and 1.3% outdoors, and on a nonlinear course, they
      were 2.7% indoors and 3.2% outdoors.

PMID- 22477437
TI  - Box for interaction with objects (BIO): a new device to synchronize the
      presentation of objects with electrophysiological recordings.
AB  - Brain event-related potentials are a useful tool for investigating visual
      processing and action planning. This technique requires extremely accurate
      synchronization of stimulus delivery with recordings. The precision of the onset
      time of visual stimulus delivery is a major challenge when attempting to use
      real, three-dimensional objects as stimuli. Here, we present an innovative
      device, the "box for interaction with objects" (BIO), that is designed to
      synchronize the presentation of objects with electroencephalographic (EEG)
      recordings. To reach the required resolution of stimulus-onset timing, the BIO
      system features an interface with reflective glass and light-emitting diodes
      (LEDs). When the LEDs inside the BIO are turned on, the object inside becomes
      visible, and a synchronizing pulse is sent to the recording systems. The BIO was
      tested in a motivational study that focused on visual and motor event-related
      potentials. EEG signals were recorded during the presentation of an emotion-laden
      object that could be grasped and brought close to the participant's chest. BIO
      successfully synchronized the appearance of a three-dimensional object with EEG
      recordings, which would allow for an analysis of visual and motor event-related
      potentials in the same experiment. The BIO device, through a high-quality
      psychophysiological approach, offers a new perspective for the study of the
      motivational factors that drive actions toward relevant stimuli.

PMID- 22477438
TI  - eDom: norming software and relative meaning frequencies for 544 English homonyms.
AB  - Words that are homonyms-that is, for which a single written and spoken form is
      associated with multiple, unrelated interpretations, such as COMPOUND, which can
      denote an < enclosure > or a < composite > meaning-are an invaluable class of
      items for studying word and discourse comprehension. When using homonyms as
      stimuli, it is critical to control for the relative frequencies of each
      interpretation, because this variable can drastically alter the empirical effects
      of homonymy. Currently, the standard method for estimating these frequencies is
      based on the classification of free associates generated for a homonym, but this
      approach is both assumption-laden and resource-demanding. Here, we outline an
      alternative norming methodology based on explicit ratings of the relative meaning
      frequencies of dictionary definitions. To evaluate this method, we collected and
      analyzed data in a norming study involving 544 English homonyms, using the eDom
      norming software that we developed for this purpose. Dictionary definitions were
      generally sufficient to exhaustively cover word meanings, and the methods
      converged on stable norms with fewer data and less effort on the part of the
      experimenter. The predictive validity of the norms was demonstrated in analyses
      of lexical decision data from the English Lexicon Project (Balota et al.,
      Behavior Research Methods, 39, 445-459, 2007), and from Armstrong and Plaut
      (Proceedings of the 33rd Annual Meeting of the Cognitive Science Society, 2223
      2228, 2011). On the basis of these results, our norming method obviates relying
      on the unsubstantiated assumptions involved in estimating relative meaning
      frequencies on the basis of classification of free associates. Additional details
      of the norming procedure, the meaning frequency norms, and the source code,
      standalone binaries, and user manual for the software are available at
      http://edom.cnbc.cmu.edu .

PMID- 22477439
TI  - TETRA-COM: a comprehensive SPSS program for estimating the tetrachoric
      correlation.
AB  - We provide an SPSS program that implements descriptive and inferential procedures
      for estimating tetrachoric correlations. These procedures have two main purposes:
      (1) bivariate estimation in contingency tables and (2) constructing a correlation
      matrix to be used as input for factor analysis (in particular, the SPSS FACTOR
      procedure). In both cases, the program computes accurate point estimates, as well
      as standard errors and confidence intervals that are correct for any population
      value. For purpose (1), the program computes the contingency table together with
      five other measures of association. For purpose (2), the program checks the
      positive definiteness of the matrix, and if it is found not to be Gramian,
      performs a nonlinear smoothing procedure at the user's request. The SPSS syntax,
      a short manual, and data files related to this article are available as
      supplemental materials from brm.psychonomic-journals.org/content/supplemental.

PMID- 22477440
TI  - Examining the convergent validity of shared mental model measures.
AB  - Despite widespread interest in shared mental models (SMMs) within teams and
      groups and an extensive empirical literature examining SMM-performance links,
      very little is known about the convergent validity of commonly used measures of
      SMMs. In this study, two-person teams (n = 96) engaged in a complex flight task
      and completed three SMM measures: concept mapping, paired ratings, and causal
      mapping. Task-based sharedness scores were compared across the measures. Analyses
      were conducted in two ways: using SMMs of actual team members (n = 96 pairs) and
      using the SMMs of pairs of participants who worked separately but for whom
      similarity indices were calculated after the study (n = 18,240). The purpose of
      the latter pairs, coined pseudo-partners, was to create a sample with
      considerable power to test the convergent validity of the SMM measures. The
      results call into some question the convergent validity of these task-based SMM
      measures.

PMID- 22477441
TI  - T cell virological synapses and HIV-1 pathogenesis.
AB  - Human immunodeficiency virus type 1 is the cause of a modern global pandemic
      associated with progressive acquired immune deficiency. The infection is
      characterized by the loss of the primary target of viral infection, the CD4+ T
      cell. The measurement of plasma viremia in patients can predict the rate of CD4+
      cell decline; however, it is not clear whether this cell-free plasma virus
      represents the engine that drives viral spread. Active viral replication is
      mainly observed within lymphoid tissues that are hotbeds of cell-cell
      interactions that initiate and organize immune responses. It is well established
      that cell-cell interactions enhance viral spread in vitro. Dendritic cell-T cell
      interactions, which lie at the heart of adaptive immune responses, enhance viral
      infection in vitro. Interactions between infected and uninfected CD4+ T cells are
      a dominant route of viral spread in vitro and are likely to play a central role
      in viral dissemination in vivo. Future studies will test existing paradigms of
      HIV-1 dissemination to determine whether virus-transmitting contacts between
      infected and uninfected T cells called virological synapses are the dominant mode
      of viral spread in vivo. Here, we review the status of our understanding of this
      mode of infection with a focus on T cell-T cell interactions and examine how it
      may explain resistance to neutralizing antibodies and or the generation of
      genetic diversity of HIV.

PMID- 22477444
TI  - Borderline peripheral arterial disease.
AB  - Peripheral arterial disease (PAD), along with coronary artery disease and
      cerebrovascular disease, is a manifestation of systemic atherosclerosis. These
      cardiovascular diseases (CVDs) are the leading cause of death in the world,
      representing 30% of all global deaths. Although population-based studies indicate
      that PAD has a relatively benign course in the legs, patients with PAD show more
      cardiovascular comorbidity and have at least twofold risk of fatal coronary
      artery disease and cerebrovascular accidents compared with the general
      population. These studies suggest that noninvasive testing using the ankle
      brachial index (ABI) is also an accurate marker of subclinical CVD and thus may
      hold promise for early identification of individuals at the greatest risk for
      major CVD events.The Inter-Society Consensus for the Management of Peripheral
      Arterial Disease (TASC II) defines a cutoff ABI value of 0.90 or less for
      diagnosing PAD at rest. This threshold value has been reported to be 95%
      sensitive in detecting angiogram-positive PAD and almost 100% specific in
      identifying apparently healthy individuals. In persons without PAD, arterial
      pressures increase with greater distance from the heart, resulting in higher
      systolic blood pressures at the ankle than at the the brachial arteries. Thus,
      persons without atherosclerosis typically have an ABI greater than 1.00. But what
      is the significance of ABI values between 0.91 to 1.00, which are conventionally
      regarded as 'no disease'? The present article gives an overview of current
      knowledge of borderline PAD (ie, an ABI of 0.91 to 1.00).

PMID- 22477442
TI  - Systematic review of proinflammatory cytokines in obsessive-compulsive disorder.
AB  - Several studies have examined levels of proinflammatory cytokines, such as tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. This meta-analysis
      was conducted to examine the association between obsessive-compulsive disorder
      (OCD) and plasma serum levels of proinflammatory cytokines. Twelve studies met
      inclusion criteria. The meta-analysis demonstrated a significant reduction in IL
      1beta levels in OCD. No significant difference in plasma levels of IL-6 or TNF
      alpha was demonstrated. Stratified subgroup analysis revealed possible moderating
      effects of age and medication use on IL-6 levels. Studies including children on
      psychotropic medication had lower plasma IL-6 levels. Stratified subgroup
      analysis revealed a moderating effect of comorbid depression on TNF-alpha levels.
      Elevated TNF-alpha levels were reported in studies that included individuals with
      comorbid depression. Future studies examining immune function in OCD should
      adjust for potential confounding due to medication use and comorbid depression.
      Further studies assessing cerebrospinal fluid cytokine levels in OCD are also
      needed.

PMID- 22477445
TI  - A viewpoint on statin effects - benefits and problems.

PMID- 22477446
TI  - Comparison of risk-scoring systems in predicting hospital mortality after
      abdominal aortic aneurysm repair.
AB  - OBJECTIVE: To compare the Physiological and Operative Severity Score for the
      enUmeration of Mortality and Morbidity, Portsmouth adjustment (P-POSSUM), the
      Hardman index and the Glasgow aneurysm score (GAS) in the prediction of hospital
      mortality after abdominal aortic aneurysm (AAA) repair. METHODS: Medical charts
      of 146 AAA patients treated between January 1996 and January 2007 were reviewed.
      The P-POSSUM, Hardman index and GAS were calculated for each patient. The scores
      were tested and compared for their discriminatory ability to predict hospital
      death. RESULTS: Of the 146 patients with ruptured and unruptured AAAs (133
      underwent open repair, five underwent extra-anatomical bypass and eight underwent
      endovascular aneurysm repair), 18 died (12%) after AAA repair. The areas under
      the receiver operating characteristic curves for the GAS, Hardman index and P
      POSSUM for predicting hospital mortality were 0.740, 0.730 and 0.886,
      respectively. The area under the receiver operating characteristic curve for the
      P-POSSUM was significantly higher than those of other scores. CONCLUSION: In the
      present study, the P-POSSUM was the best predictor of hospital mortality for
      patients undergoing AAA repair.

PMID- 22477447
TI  - Attenuation of the development of hypercholesterolemic atherosclerosis by
      thymoquinone.
AB  - Thymoquinone (TQ), derived from Nigella sativa seed, is an antioxidant. The
      present study investigated whether TQ attenuates the development of
      atherosclerosis, and/or reduces the serum lipid levels and oxidative stress in
      rabbits. New Zealand white female rabbits were assigned to four groups of six
      animals each: group I, control; group II, 1% cholesterol diet; group III, 1%
      cholesterol plus TQ (10 mg/kg/day; through a nasogastric tube) diet; and group
      IV, 1% cholesterol plus TQ (20 mg/kg/day; through a nasogastric tube) diet. Blood
      samples were collected at baseline and after four and eight weeks on the
      experimental diets for measurement of serum lipids, total cholesterol (TC),
      triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), TC/HDL-C ratio and oxidative stress biomarkers
      (malondialdehyde [MDA] and protein carbonyls). At the end of the eight weeks, the
      aorta was removed for the assessment of atherosclerotic changes, MDA and protein
      carbonyls. Group II animals developed atherosclerosis (45%+/-11% of the intimal
      surface of aorta was covered with atherosclerotic plaques), which was associated
      with an increase in the serum TC, TG, LDL-C, HDL-C, TC/HDL-C, MDA and protein
      carbonyls. In group III, TQ decreased serum TC, LDL-C, MDA and protein carbonyls
      by 26%, 29%, 85% and 62%, respectively, and aortic MDA by 73%, which was
      associated with a 40% reduction of the development of aortic atherosclerosis. The
      higher dose of TQ in group IV had effects similar to the lower dose (group III),
      except that this dose further decreased serum TG. It is concluded that TQ
      attenuates hypercholesterolemic atherosclerosis and this effect is associated
      with a decrease in serum lipids and oxidative stress.

PMID- 22477448
TI  - Nonarteritic anterior ischemic optic neuropathy treated with intravenous
      prostaglandin E1 and steroids.
AB  - BACKGROUND: Acute nonarteritic anterior ischemic optic neuropathy (NAION) is
      considered to be acute ischemia of the posterior ciliary arteries. Prostaglandin
      E1 (PGE1), a powerful microcirculation vasodilator, has been shown to improve
      ocular blood flow. DESIGN: A nonrandomized, comparative trial. METHODS: Eight
      consecutive cases of NAION were treated with intravenous steroids and PGE1. Seven
      control cases of NAION were treated with acetylsalicylic acid and oral steroids.
      Fisher's exact test was used for statistical analysis. RESULTS: The visual acuity
      improved in seven cases of NAION treated with PGE1 and was unchanged in one. Of
      the seven control cases, four had no change in vision and three lost further
      visual acuity on follow-up visits. CONCLUSIONS: Intravenous PGE1 and steroids
      should be considered in cases of NAION to immediately restore blood flow to the
      optic nerve and improve visual acuity.

PMID- 22477449
TI  - A novel approach to mechanical prophylaxis: calf impulse technology mimics
      natural ambulation more effectively than sequential calf compression.
AB  - BACKGROUND: The risk of thrombosis can be reduced by mechanical compression, but
      the optimal device is unknown. OBJECTIVES: To record the effect of natural
      ambulation on deep venous flow, providing a reference for evaluating the efficacy
      of mechanical compression systems, assuming that ambulation is the gold standard
      against which such systems should be compared; and to compare the hemodynamic
      effect of the A-V Impulse System CalfPad garment (A-VI) (Orthofix Vascular
      Novamedix, United Kingdom) with the SCD Express calf compression garment (SCD)
      (Covidien, USA). METHODS: Twelve healthy volunteers were recruited and randomly
      assigned to either A-VI or SCD in a two-device, two-period crossover design. Peak
      femoral velocity (PFV) was calculated using custom ultrasound software and
      compared with baseline values. Ultrasound images were recorded. RESULTS: A-VI
      augmented the mean (+/- SD) PFV to 59.79+/-29.07 cm/s compared with 22.86+/-5.73
      cm/s for SCD. The actual percentage increase from baseline was approximately five
      times greater for A-VI (mean increase 385%+/-260%) than SCD (mean increase 81%+/
      53%). Using an analysis of covariance model, with baseline fitted as a covariate,
      a highly statistically significant difference in favour of A-VI was detected
      (P=0.0002). Least square (adjusted) means (+/-95% CIs) were 37.24 cm/s (21.39
      cm/s to 64.84 cm/s) for A-VI and 6.71 cm/s (3.86 cm/s to 11.69 cm/s) for SCD,
      representing more than fivefold greater improvement in PFV from rest with the A
      VI device than with the SCD device. CONCLUSION: Pulsatile impulse calf
      compression (A-VI) more closely mimics PFV of normal ambulation than slow-squeeze
      sequential compression (SCD). Pulsatile calf compression may provide superior
      protection against thrombosis in immobile patients.

PMID- 22477450
TI  - Impact of atherosclerosis risk factors on the clinical presentation of arterial
      occlusive disease in Arabic patients.
AB  - BACKGROUND: Although the risk factors for atherosclerosis have been identified,
      their impact on the presentation of arterial occlusive disease has not been
      studied among Arabs. OBJECTIVE: To determine the correlation between
      atherosclerotic risk factors and the extent and presentation of atherosclerotic
      disease in different arterial systems. METHODS: The present case-control study
      was performed on a consecutive series of Arabic patients over one year. There
      were two groups - an atherosclerotic group, which included patients with
      peripheral arterial disease, extracranial cerebrovascular disease or coronary
      artery disease (CAD), and the control group, which included patients admitted to
      one of the general surgical units who were free from atherosclerotic disease. All
      patients underwent evaluation of risk factors (diabetes mellitus [DM], smoking,
      dyslipidemia and hypertension) for atherosclerosis and systemic assessment of the
      vascular tree. RESULTS: Two hundred fifteen patients in the atherosclerotic group
      and 191 patients in the control group were included in the study. There were
      positive correlations between the prevalence of DM, smoking, dyslipidemia and the
      severity of presentation of peripheral arterial disease, and the extent of CAD.
      The correlation between the incidence of DM and the severity of presentation of
      CAD was also significant. The correlation was also positive between the incidence
      of ex-smoking and hypertension, and the severity of presentation of extracranial
      cerebrovascular disease. CONCLUSION: Different risk factors may interact in
      different ways in the clinical presentation of atherosclerotic disease in
      different arterial systems.

PMID- 22477451
TI  - Carotid artery stenting in asymptomatic and surgically high-risk patients: single
      centre, single-operator results.
AB  - BACKGROUND: Stroke represents the third leading cause of death in developed
      countries and the leading cause of disability in the elderly. Because
      asymptomatic, surgically high-risk patients have been systematically excluded
      from randomized trials of carotid endarterectomy and medical therapy, the
      management of this group of patients is still controversial. A single-centre,
      single-operator registry was analyzed to evaluate feasibility and safety of
      carotid artery stenting (CAS) with distal protection devices in consecutive,
      asymptomatic, surgically high-risk patients who were scheduled for endovascular
      treatment of significant carotid stenoses. METHODS: A total of 122 consecutive,
      surgically high-risk, asymptomatic patients (150 carotid arteries, 59% men, mean
      [+/- SD] age 69+/-9 years) with severe carotid stenosis and one or more high-risk
      features for carotid endarterectomy were scheduled for CAS. All procedures were
      performed in a single centre by a single operator. All patients were
      prospectively asked to undergo a clinical 30-day follow-up. RESULTS: A total of
      154 stents were implanted in 150 carotid arteries. The primary success rate was
      98.7%. The rates of stenosis before and after direct CAS were 81%+/-9% and 10%+/
      13%, respectively. The median of fluoroscopic time of direct CAS was 6 min (range
      2.5 min to 31.5 min). At 30 days, data were available in all patients. The
      combined 30-day mortality and stroke rate was 1.3%. CONCLUSIONS: Short-term
      outcomes of CAS in asymptomatic, surgically high-risk patients treated by a
      single operator suggest a low periprocedural complication rate.

PMID- 22477452
TI  - Arteriovenous malformation of the pancreas: A case report and review of
      literature.
AB  - Extrahepatic arteriovenous malformations (AVMs) of the gastrointestinal (GI)
      tract are rare and mostly asymptomatic congenital anomalies. The present case
      describes a 45-year-old woman with an AVM in the head of the pancreas, which
      caused massive GI bleeding that recurred after embolization, and which was
      subsequently treated with a pylorus-preserving Whipple pancreaticoduodenectomy.
      The authors then review the available literature pertaining to AVMs of the GI
      tract, the diagnostic modalities that have been used to identify them and the
      treatment approaches that have been described to date, which range from coil
      embolization of the feeding artery to radical resection of the affected organ. It
      is important to remember that these lesions shunt blood between the high-pressure
      arterial system and the low-pressure portal system, which leads to the much
      dreaded consequence of portal hypertension.

PMID- 22477453
TI  - Diagnosis and management of acute traumatic arteriovenous fistula.
AB  - Acute arterial injuries are often complicated by the development of an
      arteriovenous fistula (AVF). In the acute setting, an AVF may present at the same
      time as the arterial injury. A case of traumatic AVF in the thigh that presented
      with normal neurovascular examination findings is reported. AVF was diagnosed by
      duplex scan and managed promptly. The authors suggest that duplex imaging
      together with arteriography, where appropriate, should be performed routinely
      when penetrating wounds are in close proximity to major vessels despite a normal
      clinical neurovascular examination.

PMID- 22477454
TI  - Post-traumatic giant fistula between the aorta and the left renal vein: a case
      report.
AB  - A unique case of post-traumatic aorto-left renal vein fistula (ALRVF) is
      presented. Some specific features of diagnosis and treatment of post-traumatic
      and postaneurysm ALRVF are discussed. The importance of careful planning of the
      operative strategy is emphasized because substantial blood loss may lead to
      serious intraoperative complications and frequently necessitates
      autohemotransfusion. The 10-year follow-up confirmed that direct reconstruction
      was the appropriate procedure, with no indications that an endovascular procedure
      would have been preferable. Direct reconstruction may also be valuable in
      treating postaneurysm ALVRF.

PMID- 22477455
TI  - Edaravone suppresses endothelial cell injury in vein grafts of a rat model.
AB  - OBJECTIVE: Postoperative intimal hyperplasia, the major cause of vein graft
      occlusion, is initiated by endothelial injury. Using a high-magnification
      scanning electron microscope (SEM), the surfaces of endothelial cells in vein
      grafts were examined to investigate the protective mechanism of the free radical
      scavenger edaravone (Radicut, Mitsubishi Tanabe Pharma Co, Japan) against
      endothelial injury in postoperative intimal hyperplasia. METHODS: In 10 male
      Lewis rats with a mean (+/- SD) weight of 495+/-28 g, a right epigastric vein
      graft was interposed into the common femoral artery. Five rats received
      preoperative intraperitoneal administration of edaravone (3.0 mg/kg; edaravone
      group). The other five received an equal volume of saline preoperatively (sham
      operation group). Unoperated right epigastric veins were also examined as
      controls. The vein grafts from each group were examined using an S-800 Hitachi
      SEM (Hitachi High-Technologies Co, Japan) at *10,000 to *20,000 magnification.
      RESULTS: Unoperated endothelial cells had smooth surfaces. While endothelial
      cells in the sham operation group had very rough surfaces with platelet adhesion,
      endothelial cells in the edaravone group had smooth surfaces without platelet
      adhesion, very similar to unoperated endothelial cells. CONCLUSION: These SEM
      results showed that edaravone may maintain the smooth surface of endothelial
      cells. The authors postulate that edaravone suppresses postoperative intimal
      hyperplasia by alleviating endothelial injury.

PMID- 22477457
TI  - Editorial.

PMID- 22477456
TI  - Lisuride reduces involuntary periodic leg movements in spinocerebellar ataxia
      type 2 patients.
AB  - Periodic leg movements (PLMs) are a common sleep disorder in spinocerebellar
      ataxia type 2 (SCA2) being associated to higher disease severity and altered
      sleep patterns. To assess the efficacy and safety of lisuride for the treatment
      of PLMs in SCA2 patients, an open-label clinical trial was conducted in 12 SCA2
      patients suffering from PLMs associated to other subjective sleep complaints. All
      subjects received 0.1 mg of oral lisuride daily for 4 weeks. Primary outcome
      measure was the change of PLMs index. Changes in the subjective sleep quality,
      other polysomnographical sleep parameters, Scale for the Assessment and Rating of
      Ataxia score, and saccadic velocity were assessed as secondary outcome
      parameters. Safety assessments included hemoglobin, hematocrit, cholesterol,
      creatinine, and TGP. A significant decrease in both the PLMs index and R stage
      latency were observed during the treatment, associated to subjective improvement
      of frequent awakenings, early insomnia, restless leg syndrome, and nocturnal limb
      paresthesias in most cases. Ataxia score and saccadic pathology were unchanged.
      No significantly adverse events were observed. Our study suggests the efficacy of
      dopamine agonist therapy in the treatment of PLMs in SCA2, improving various
      subjective sleep complaints. These findings serve to promote the adequate
      management of sleep-related disorders in SCA2, which could improve the life
      quality of the patients.

PMID- 22477458
TI  - An assessment of self-echoic behavior in young children.
AB  - In the behavioral literature, self-echoic behavior has been hypothesized to play
      an important role in, for example, emergent conditional discriminations (e.g.,
      Lowenkron, 1991), emergent verbal operants (Horne & Lowe, 1996), and problem
      solving (Skinner, 1957). Although early behavioral intervention programs for
      children with autism emphasize the establishment of accurate echoic repertoires,
      the type of stimulus control that defines a self-echoic response is typically not
      addressed. We report the development of a self-echoic assessment procedure that
      was administered to children with and without autism spectrum disorders.
      Preliminary results indicated that a discrepancy between echoic and self-echoic
      repertoires was more likely to be present among participants with autism than
      among typically developing participants. Future research should evaluate the
      extent to which interventions to establish self-echoic responding might produce
      other collateral benefits.

PMID- 22477459
TI  - Evaluation of single and mixed verbal operant arrangements for teaching mands and
      tacts.
AB  - The purpose of this series of experiments was to evaluate the effects of mixed
      mand-tact arrangements on the acquisition of mands and tacts in preschool-aged
      children. In Experiment 1, the effects of three training arrangements (mand-only
      training, tact-only training, and mand-tact training) were investigated with 3
      typically developing children. Rates of acquisition in single (mand-only and tact
      only) versus mixed (mand-tact) presentation were comparable, in contrast to
      earlier investigations. Experiment 2 attempted to clarify the equivocal findings
      of Experiment 1 by directly replicating the Carroll and Hesse (1987)
      investigation with 2 typically developing children. Results again demonstrated no
      clear benefit of mixed verbal operant training on tact acquisition. In Experiment
      3, these same arrangements were evaluated with a boy with autism and included
      assessments to determine that a relevant establishing operation was in effect
      prior to each mand training session. Experiment 3 again failed to demonstrate the
      facilitative effects of mand-tact training on the acquisition of mands or tacts.
      Taken together, the data from these three experiments fail to support the
      improved efficiency of mand-tact training suggested by prior studies. Findings
      are discussed in the context of future research investigating mixed verbal
      operant arrangements.

PMID- 22477460
TI  - The effects of textual prompting and reading fluency on the acquisition of
      intraverbals.
AB  - The study examined the effects of textual prompt fading on the acquisition of
      intraverbals in 3 individuals with developmental disabilities. An alternating
      treatments design was used to assess the two independent variables. The first
      independent variable was transfer of stimulus control without component skill
      fluency. The second independent variable was transfer of stimulus control with
      component skill fluency, in which participants were taught the textual responses
      used in the scripts to a level of fluency prior to transfer of stimulus control.
      The results suggest that transfer of stimulus control was effective for teaching
      intraverbals and that adding a fluency component resulted in faster acquisition
      for some participants.

PMID- 22477461
TI  - Defining delayed consequences as reinforcers: some do, some don't, and nothing
      changes.
AB  - Results of a survey sent to members of the editorial boards of five behavior
      analytic journals in 1990 indicated that there was no consensus among respondents
      with respect to whether delayed events can function as reinforcers (Schlinger,
      Blakely, Fillhard, & Poling, 1991). Since that time, several studies with
      nonhuman animals have demonstrated that events delayed by at least several
      seconds can increase the probability of occurrence of the responses that produce
      them. To determine the relative number of contemporary behavior analysts who
      nonetheless believe that reinforcers must immediately follow the responses that
      produce them, the present study replicated the procedures used by Schlinger et
      al., with similar results. That is, respondents did not agree with respect to
      whether delayed events could be reinforcers.

PMID- 22477462
TI  - Recombinative generalization: an exploratory study in musical reading.
AB  - The present study aimed to extend the findings of recombinative generalization
      research in alphabetical reading and spelling to the context of musical reading.
      One participant was taught to respond discriminatively to six two-note sequences,
      choosing the corresponding notation on the staff in the presence of each
      sequence. When novel three- and four-note sequences were presented, she selected
      the corresponding notation. These results suggest the generality of previous
      research to the context of musical teaching.

PMID- 22477463
TI  - Enhancing vowel discrimination using constructed spelling.
AB  - In a computerized task, an adult with intellectual disabilities learned to
      construct consonant-vowel-consonant words in the presence of corresponding spoken
      words. During the initial assessment, the participant demonstrated high accuracy
      on one word group (containing the vowel-consonant units it and un) but low
      accuracy on the other group (containing the units ag and ed). Errors occurred
      almost exclusively in the vowel position. Training the group with low accuracy
      increased accuracy on the trained word group but decreased the accuracy on the
      untrained, but initially accurate, group. High accuracy on both groups together
      occurred only after added training in which all five vowels (a, e, i, u, and o)
      were taught together in words that differed only in the vowel. These findings
      indicate the importance of carefully arranging examples and nonexamples to
      sharpen stimulus control. The findings also illustrate a promising step in the
      development of effective instructional programming for remediation of medial
      vowel errors, which can be a source of difficulty in early reading instruction.

PMID- 22477464
TI  - The effects of listener training on the emergence of tact and mand signs by
      individuals with intellectual disabilities.
AB  - The purpose of the current study was to assess whether individuals with
      intellectual disabilities would emit untrained speaker responses (i.e., signed
      tacts and mands) after being taught listener behaviors. Listener relations were
      trained via an automated matching-to-sample (MTS) procedure. Following mastery,
      the emergence of signed tacts, generalized tacts, and mands was tested. All
      participants met criterion in listener relations training and showed the
      emergence of almost all relations. Results suggest that teaching listener
      relations first, through MTS tasks, is a viable way to produce emergence of
      speaker relations.

PMID- 22477465
TI  - A rose by naming: how we may learn how to do it.
AB  - Naming appears to be the source of the explosion in language development and
      involves the integration of the initially separate listener and speaker
      responses. This integration has a role in the development of reading, writing,
      and the following and construction of verbal algorithms that make types of
      complex human behavior possible. Considerable research has investigated the role
      of Naming in the emergence of derived relations. Recent research has also
      investigated the emergence of Naming itself. We describe these experiments and
      the experiences that function to induce Naming. We also describe evidence about
      preverbal developmental cusps that are foundational to the emergence of Naming
      and the evidence on its reinforcement sources. The isolation of the role of the
      environment in the emergence of Naming identifies stimuli that were said to be
      missing in accounts that were critical of Skinner's (1957) account of verbal
      behavior. These arguments purported that the phenomenon was not attributable to
      learning because of the "poverty of the stimulus." Some of the relevant stimuli
      now appear to be identified.

PMID- 22477466
TI  - Three myths from the language acquisition literature.
AB  - THREE POPULAR ASSERTIONS HAVE HINDERED THE PROMOTION OF AN EMPIRICIST APPROACH TO
      LANGUAGE ACQUISITION: (a) that Brown and Hanlon (1970) claimed to offer data that
      parents do not reinforce their children's grammaticality; (b) that Brown and
      Hanlon also claimed to offer data that parents do not provide negative evidence
      (i.e., corrective feedback) for ungrammaticality; and (c) that Gold (1967)
      claimed to offer a formal proof showing that, without negative evidence, a child
      cannot acquire a language solely from environmental input. In this paper I offer
      introductory comments on the nature-nurture distinction (including
      interactionism, and the nativists' claim to have found a gene for language). Next
      I debunk the three aforementioned assertions by arguing that the authors (Brown &
      Hanlon; Gold) never made the claims attributed to them; review evidence on the
      role of reinforcement and corrective feedback in language acquisition; and offer
      some concluding comments.

PMID- 22477467
TI  - Crucial issues in the applied analysis of verbal behavior: reflections on crucial
      conversations: tools for talking when the stakes are high.
AB  - A popular-press self-help manual is reviewed with an eye toward two issues.
      First, the popularity of such books documents the existence of considerable
      demand for technologies that address the everyday problems (in the present case,
      troublesome conversations) of nondisordered individuals. Second, many ideas
      invoked in popular-press books may be interpretable within an analysis of verbal
      behavior, although much more than casual translation is required to develop
      technologies that outperform self-help manuals. I discuss several challenges
      relevant to research, theory refinement, technology development, and
      dissemination, and conclude that behavioral alternatives to existing popular
      press resources may not emerge anytime soon.

PMID- 22477468
TI  - Daytime secretion of salivary cortisol and alpha-amylase in preschool-aged
      children with autism and typically developing children.
AB  - We examined daytime salivary cortisol and salivary alpha-amylase (sAA) secretion
      levels and variability in preschool-aged children with autism (AUT) and typically
      developing children (TYP). Fifty-two subjects (26 AUT and 26 TYP) were enrolled.
      Salivary samples were obtained at waking, midday, and bedtime on two consecutive
      days at three phases (baseline, 3 months later, 6 months later). There were
      modest increases in waking cortisol and sAA levels in AUT relative to TYP, but
      the increases were not statistically significant. Important differences were
      observed in cortisol and sAA variability between AUT and TYP. There was also a
      graded response among AUT by functional status--cortisol and sAA secretion levels
      were higher when IQ was lower.

PMID- 22477469
TI  - Characterization of photosystem I from spinach: effect of solution pH.
AB  - Our previous work has demonstrated the isolation of photosystem I (PSI) from
      spinach using ultrafiltration with a final purity of 84%. In order to get a
      higher purity of PSI and more importantly to develop a practical bioseparation
      process, key physiochemical properties of PSI and their dependence on operational
      parameters must be assessed. In this study, the effect of solution pH, one of the
      most important operating parameters for membrane process, on the property of PSI
      was examined. Following the isolation of crude PSI from spinach using n-dodecyl
      beta-D: -maltoside as detergent, the isoelectric point, aggregation size, zeta
      potential, low-temperature fluorescence, atomic force microscopy imaging,
      secondary structure, and thermal stability were determined. Solution pH was found
      to have a significant effect on the activity, aggregation size and thermal
      stability of PSI. The results also suggested that the activity of PSI was related
      to its aggregation size.

PMID- 22477471
TI  - A novel method of coronary stent sizing using intravascular ultrasound: Safety
      and clinical outcomes.
AB  - OBJECTIVES: The use of intravascular ultrasound (IVUS) in guiding coronary
      stenting has increased in recent years. The feasibility, safety and clinical
      outcomes of a novel method of sizing coronary stents using IVUS have not been
      established. The main end points of the current study are the incidence of acute
      and short-term complications, and the need for target vessel revascularization at
      six months. METHODS: Eighty-six patients underwent coronary stenting using IVUS
      imaging during the procedure. The optimal size of the stents was determined by
      using a novel method (the 'aggressive IVUS method'), ie, measuring the media-to
      media dimensions of the coronary vessels at the site of the lesions using IVUS. A
      six-month follow-up chart review was performed following the initial stenting.
      RESULTS: At six months, there were two noncardiac deaths in the group. There were
      no acute, subacute or late stent thromboses. Target vessel revascularization and
      major adverse cardiac event rates remained low - at 5.8% and 9.3%, respectively.
      The mean (+/- SD) IVUS-derived coronary stent size (3.89+/-0.98 mm) using the
      aggressive IVUS method was significantly different from the mean IVUS-derived
      coronary stent size (3.46+/-0.96 mm) using the 'traditional IVUS method'.
      CONCLUSION: Aggressive sizing of the coronary stents by IVUS guidance is feasible
      and safe, and is associated with a favourable clinical outcome.

PMID- 22477472
TI  - External banding valvuloplasty for incompetence of the great saphenous vein: 10
      year results.
AB  - OBJECTIVES: External banding valvuloplasty (EBV) of the great saphenous vein
      (GSV) in patients with varicose veins is still controversial. The present study
      evaluated the effectiveness of EBV in selected patients with an insufficiency of
      the GSV after a mean follow-up of 92.6 months. METHODS: A total of 101 limbs
      underwent EBV for the treatment of a GSV insufficiency. Thirty-one limbs from 27
      patients (three men, 24 women; mean age 44.2 years; range 19 to 58 years) were re
      examined and followed for a mean of 92.6 months. The venous volume, venous
      filling index, ejection fraction and residual venous fraction were analyzed
      preoperatively and at the follow-up using air plethysmography. The diameter and
      reflux of the GSV were evaluated using duplex ultrasound. RESULTS: Overall, the
      mean (+/- SD) follow-up time was 92.6+/-22.3 months (range 46 to 138 months). At
      the follow-up, the preoperative venous hemodynamic states had improved
      significantly, to the following values: venous volume 96.0+/-32.3 mL to 83.4+/
      32.6 mL; venous filling index 3.6+/-2.9 mL/min to 2.4+/-2.2 mL/min; and residual
      venous fraction 39.7%+/-18.6% to 26.1%+/-16.8% (P<0.05). The diameter of the GSV
      was 6.4+/-1.4 mm preoperatively and 4.8+/-1.7 mm postoperatively (P<0.01). Reflux
      in the proximal GSV was demonstrated preoperatively in 19 (61.3%) of 31 limbs.
      During the follow-up period, four limbs (12.9%) had high ligation and stripping
      of the GSV performed due to the recurrence of varicosity. CONCLUSION: EBV of the
      GSV provides good results in terms of the venous hemodynamics and decreasing the
      diameter of the GSV. EBV may be an alternative procedure to stripping or
      endovenous ablation therapy in selected patients.

PMID- 22477473
TI  - Arteriovenous fistulas as vascular access for hemodialysis: The preliminary
      experience at the University Hospital of the West Indies, Jamaica.
AB  - BACKGROUND: The demand for vascular hemodialysis access creation is steadily
      increasing. To satisfy the demand, a vascular access team was established at the
      University Hospital of the West Indies, Jamaica. The outcomes of this practice
      are reported. METHODS: A retrospective study of all patients who had permanent
      vascular dialysis access established at the University Hospital of the West
      Indies between January 1, 2002, and December 31, 2006, was performed. Data were
      analyzed using SPSS version 12.0 (SPSS Inc, USA). A direct anastomosis between an
      autogenous artery and vein was considered an arteriovenous fistula (AVF). When
      prosthetic material was used, the access was considered to be an arteriovenous
      graft. Accesses that were nonfunctional after six weeks of maturation were
      considered to be primary failures, while those that failed after previous
      successful dialysis were considered to be secondary failures. Primary patency was
      defined as the interval between access placement and the first intervention for
      failure. Secondary patency was the interval between access placement and
      abandonment. Cumulative patency was defined as the number of accesses that
      remained patent over a given time period, regardless of the number of
      interventions performed. RESULTS: Of 41 patients, nine were excluded due to
      incomplete data. Final analyses were performed on 32 patients with a mean (+/-
      SD) age of 42.3+/-15.3 years (range 18 to 66 years, median 43 years). The access
      type was an AVF in 100% of cases, which included distal radiocephalic fistulas in
      27 patients, brachial-cephalic fistulas in three patients and proximal
      radiocephalic fistulas in two patients. Operations were performed in four (12.5%)
      incident and 28 (87.5%) prevalent dialysis patients. The mean delay between
      initiation of dialysis and AVF creation was 21.2+/-26.1 months (range one to 94
      months, median 10 months). There were eight (25%) primary failures. Of the
      remaining 24 patients, there were seven (29.2%) secondary failures from
      thrombosis. There was primary patency for a mean of 723.9+/-422.1 days (range 199
      to 1314 days, median 678 days). Only one (4.2%) patient had thrombectomy to
      prolong AVF function, resulting in secondary patency for 439 days. Cumulative
      patency was 62.5%, 33.3%, 25% and 4.2% for one, two, three and four years,
      respectively. CONCLUSIONS: The rate of AVF creation for end-stage renal disease
      patients in this setting far exceeds the target goals set forward by the National
      Kidney Foundation published updated Dialysis Outcomes Quality Initiative
      (NKF/DOQI) Guidelines and the Centers for Medicaid & Medicare Services Fistula
      First initiative. This is being achieved with acceptable rates of morbidity and
      patency. There is room for improvement in postoperative surveillance to increase
      early detection of failing accesses and allow for increased utility of
      interventions for assisted patency.

PMID- 22477474
TI  - Forty years' experience treating septic arteritis and vasculitis.
AB  - By their natures, septic arteritis and infected grafts present a high morbidity
      and mortality situation for both the patient and the treating physician. In the
      experience of the authors, therapy frequently includes removing the previous
      infected graft, use of long-term antibiotics, repeat grafting and omental wraps.
      When possible, aortic endografting followed by future elective primary repair may
      be considered an option. Leaving wounds open to granulate from the 'bottom up'
      has been successful in the extremities and the groin. Again, avoidance of
      infection is primary. Antibiotics are frequently used at the time of vascular
      grafting, both intravenously and as irrigation. Examples of the authors'
      techniques and results demonstrate the variety of procedures available.

PMID- 22477470
TI  - The antihypertensive effect of cysteine.
AB  - Hypertension is a leading cause of morbidity and mortality worldwide. Individuals
      with hypertension are at an increased risk for stroke, heart disease and kidney
      failure. Essential hypertension results from a combination of genetic and
      lifestyle factors. One such lifestyle factor is diet, and its role in the control
      of blood pressure has come under much scrutiny. Just as increased salt and sugar
      are known to elevate blood pressure, other dietary factors may have
      antihypertensive effects. Studies including the Optimal Macronutrient Intake to
      Prevent Heart Disease (OmniHeart) study, Multiple Risk Factor Intervention Trial
      (MRFIT), International Study of Salt and Blood Pressure (INTERSALT) and Dietary
      Approaches to Stop Hypertension (DASH) study have demonstrated an inverse
      relationship between dietary protein and blood pressure. One component of dietary
      protein that may partially account for its antihypertensive effect is the
      nonessential amino acid cysteine. Studies in hypertensive humans and animal
      models of hypertension have shown that N-acetylcysteine, a stable cysteine
      analogue, lowers blood pressure, which substantiates this idea. Cysteine may
      exert its antihypertensive effects directly or through its storage form,
      glutathione, by decreasing oxidative stress, improving insulin resistance and
      glucose metabolism, lowering advanced glycation end products, and modulating
      levels of nitric oxide and other vasoactive molecules. Therefore, adopting a
      balanced diet containing cysteine-rich proteins may be a beneficial lifestyle
      choice for individuals with hypertension. An example of such a diet is the DASH
      diet, which is low in salt and saturated fat; includes whole grains, poultry,
      fish and nuts; and is rich in vegetables, fruits and low-fat dairy products.

PMID- 22477475
TI  - Percutaneous common iliac artery aneurysm repair - a case report.
AB  - Endovascular repair of common iliac artery aneurysms has become the preferred
      form of treatment, provided the appropriate anatomy for endovascular repair
      exists. The Zenith abdominal aortic aneurysm graft converter (Cook Medical Inc,
      USA), by virtue of its design, appears to be the ideal device for such a repair.
      A case to illustrate the same is presented.

PMID- 22477476
TI  - Endovascular repair of post-traumatic, concomitant popliteal artery
      pseudoaneurysm and arteriovenous fistula.
AB  - Popliteal artery trauma is a potentially devastating injury to the lower
      extremity with substantial associated morbidity. Pseudoaneurysm and arteriovenous
      fistula formation are complications of arterial injury that often present in a
      delayed fashion. Although these have traditionally been repaired using an open
      procedure, the growth of minimally invasive techniques has provided new
      therapeutic options for the treatment of such lesions. The present report
      discusses the successful treatment of concomitant popliteal pseudoaneurysm and
      arteriovenous fistula after delayed presentation by placing covered stents
      endovascularly.

PMID- 22477477
TI  - Premature peripheral arterial disease - difficult diagnosis in very early
      presentation.
AB  - Peripheral arterial disease (PAD) is defined as an ankle-brachial index of less
      than 0.9. It is mostly prevalent in patients older than 50 years of age; its
      occurrence in younger patients is rare. Nevertheless, the diagnosis must be
      considered in any patient with exertional lower extremity symptoms. Patients with
      early-onset disease, also called premature PAD, have a particularly difficult
      course with early involvement of other major arterial beds such as the carotid
      and coronary arteries. Their diagnosis and treatment have to be comprehensive to
      prevent early morbidity and mortality. Reports of very early occurrence and
      management are rare, especially of onset before 25 years of age. Management of
      this early presentation of PAD is unclear because most of the available
      information concerns treatment of patients 40 years of age or older. The cases of
      two patients who developed symptomatic PAD before 25 years of age are described,
      and the various causes and management options available for the treatment of
      early onset PAD patients are discussed.

PMID- 22477478
TI  - Unique operative approach for dealing with a tortuous external iliac artery
      during abdominal aortic aneurysm endografting.
AB  - Endovascular repair of abdominal aortic aneurysms offers many benefits over open
      repair. However, there are many characteristics that can exclude patients from
      undergoing this minimally invasive procedure, such as iliac arterial pathology.
      The present report describes the case of an 85-year-old patient with an aneurysm
      in which the right external iliac artery presented a challenge for vascular
      access due to its severe tortuosity and hairpin turn. Access for endovascular
      repair was achieved via an end-to-end anastomosis of the external iliac artery
      through a transverse inguinal incision. This represents a new option for
      achieving endograft placement when confronted with vascular tortuosity.

PMID- 22477479
TI  - [About traditions ...the 65th Anniversary of the Respiratory Diseases Clinic
      "Heckeshorn" (Chest-Hospital)].

PMID- 22477480
TI  - [Interferon-gamma release assays for hospital-based tuberculosis diagnostics in
      children and adolescents--a retrospective analysis].
AB  - OBJECTIVE: Interferon-gamma release assays (IGRA) are well established for
      diagnosing latent tuberculosis infection in adults. Evidence for their diagnostic
      relevance in children is still insufficient. The aim of this study was to
      evaluate the sensitivity and specificity of IGRA compared to the tuberculin skin
      test (TST) in a local population of children and adolescents presenting to our
      lung clinic with a specialised outpatient department. METHODS: Records from all
      patients evaluated for tuberculosis at our centre between 2009 and 2011 were
      analysed retrospectively. Complete data sets were available for 80 children and
      adolescents (age 3 months to 17 years) in the following diagnostic groups: active
      pulmonary tuberculosis (MTB, n = 13), latent tuberculosis infection (LTBI, n =
      15) and controls with tuberculosis exposure (n = 40), non-tuberculous
      mycobacterial disease (NTM, n = 2) or other lung diseases (n = 10). RESULTS: All
      13 patients with MTB were positive on both IGRA and TST. Among the LTBI patients,
      14 /15 had a positive IGRA and 14 /15 a positive TST result. In the control group
      0 /52 exceeded the IGRA cut-off, while three patients had a positive TST due to a
      cross reaction with BCG or NTM. DISCUSSION: IGRA and TST results are highly
      correlated in paediatric patients with active or latent tuberculosis. IGRA
      sensitivity was comparable to that of the TST with a higher specificity as
      expected. The importance of IGRA in the hospital setting to guide diagnostic
      algorithms in an unselected population should be further evaluated in prospective
      studies.

PMID- 22477481
TI  - [Staging with 18F-FDG-PET/CT influences stage-specific survival in advanced non
      small cell lung cancer (NSCLC)].
AB  - BACKGROUND: PET/CT investigation with 18F-fluorodeoxyglucose (FDG) has a high
      sensitivity (89 - 100 %) and good specificity (79 - 95 %) for the diagnosis of
      NSCLC. Currently, it is mainly used in preoperative staging. This leads in
      approximately 15 % of these cases to the diagnosis of metastatic disease that was
      neither clinically suspected nor seen in previously performed conventional
      imaging. We hypothesised that including these cases in the palliative stage IV
      group would have an influence on overall survival. AIM: The aim of this study was
      to compare the overall survival (OS) of patients with stage IV NSCLC who
      underwent FDG-PET/CT staging with patients in whom conventional imaging
      procedures were performed. METHODS: We analysed the OS of all stage IV NSCLC
      patients diagnosed in our clinic in 2009 (n = 254), 96/254 (38 %) patients were
      staged with PET/CT and 158/254 (62 %) with conventional imaging (CT group).
      Survival data were compared by Kaplan-Meier statistics. RESULTS: Patients in the
      PET/CT group were younger (65 +/- 11) than in the CT group (68 +/- 10 years; p =
      0.008). The median OS of all patients was 246 (range: 217 - 275) days; 338
      (range: 247 - 429) days in the PET/CT group and 207 (range: 161 - 253) days in
      the CT group (p = 0.001), stating a difference of 131 days (4.4 months) in median
      OS. CONCLUSION: The use of FDG-PET/CT staging mainly in the preoperative setting
      leads to stage migration of patients with a better prognosis into the worst stage
      (IV) and thus longer survival within this subgroup. This survival benefit is
      unrelated to treatment and needs to be addressed in future studies.

PMID- 22477482
TI  - [Curative surgical treatment options for patients with non-small cell lung cancer
      (NSCLC) and solitary pulmonary metastasis].
AB  - INTRODUCTION: The treatment of synchronous solitary lung metastasis in non-small
      cell lung cancer (NSCLC) remains controversial. Satellite lesions in the same
      lobe are now classified as T3 which may result in stage IIB (T3N0M0). In
      contrast, ipsilateral lesions in different lobes are associated with a worse
      prognosis and classified as T4 tumors (stage IIIA), but operation is usually
      withheld from these patients. Contralateral lung metastases have been classified
      more recently as M1a which usually results in a conservative therapy. We analysed
      survival data of all patients with primary lung tumour and synchronous pulmonary
      metastasis outside of the tumour-bearing lobe, who underwent surgery. METHODS:
      Between 1997 - 2007 we operated on 57 patients with NSCLC and simultaneous second
      (solitary) malignant lesions of the lung, outside of the tumour-bearing lobe,
      after informed consent. Survival was documented and analysed by Kaplan-Meier
      statistics (log-rank). RESULTS: The primary tumour was treated in 67 % of cases
      by lobectomy, in 9 % by pneumonectomy, by bilobectomy in 2 % and in 22 % by
      segment or wedge resection. The second malignant lesion, and thus potential
      solitary metastasis, was treated in 83 % by segment or wedge resection. The
      overall survival of all patients (n = 57) was a median of 82 months (75 - 89
      95%CI). In the synchronous second primaries (n = 7) the median survival was 76
      months (0.1 to 151 95%CI) and in the synchronous metastases (n = 50) 82 months
      (95 % CI 75 - 88). This results in a 5-year survival rate of 56 % and 77 %,
      respectively. The median survival of patients with solitary metastasis,
      ipsilateral (T4 after UICC7) was 79 months (76 - 82 95 %CI) and with
      contralateral metastasis (M1a according UICC7) 84 months (60 - 107 95 %CI, p =
      0.634). CONCLUSIONS: This analysis shows that patients with solitary pulmonary
      metastasis (outside of the tumour-bearing lobe) and otherwise operable NSCLC may
      profit from surgical intervention comprising resection of the primary tumour,
      lymphadenectomy, and resection of the solitary pulmonary metastasis. Long-term
      survival can be achieved independent of the localisation of lung metastases
      (ipsilateral vs. contralateral lung).

PMID- 22477483
TI  - [Rational tumour documentation and quality assurance to improve the standard of
      medical care for lung cancer patients].
AB  - The data on the quality of care of patients with lung cancer in Germany are
      insufficient. Although the National Lung Cancer Guideline from 2010 provides a
      good scientific basis for the management of the frequently complex pathways, no
      evidence exists showing how the relevant guideline recommendations are
      implemented nationwide or which treatment options generally are chosen in a
      tumour entity with one of the poorest prognoses. As part of the National Cancer
      Plan 2008, specific targets have been formulated for the systematic improvement
      of cancer care in Germany. As a main goal, the national re-organisation and
      harmonisation of tumor documentation and quality assurance are required for a
      sustainable improvement in the quality of care. This review article first
      describes the relevant terms and then examines how the specific targets of the
      National Cancer Plan have been implemented so far with regard to lung cancer
      care.

PMID- 22477484
TI  - [The need for palliative care treatment in pneumology in non-malignant diseases-
      a case report].
AB  - A 70-year-old pneumological patient with a COLD for many years, who was using
      long-term oxygen therapy, developed a complex clinical presentation. During his
      inpatient course over several weeks we treated severe physical symptoms such as
      shortness of breath, anxiety and pain. After the transfer to the palliative care
      ward only an inpatient final accompaniment was possible. In this case the
      palliative care expertise was integrated too late into the process of the
      therapy. The delay led to a poorer control of severe physical symptoms such as
      those named above. Also, the patients request for comprehensive ambulant care
      could not be realised because the severity of the disease was not detected soon
      enough. Instruments for the evaluation of the need for an additional palliative
      care treatment in patients with a non-malignant pneumological disease have not
      been established sufficiently.

PMID- 22477485
TI  - [Implementation of an early geriatric rehabilitation in acute inpatient
      pneumology].
AB  - BACKGROUND: In order to counter the rapidly developing loss of function
      especially in elderly patients with acute exacerbation of chronic obstructive
      pulmonary disease (AE-COPD) the concept "early geriatric rehabilitation in acute
      inpatient pneumology" was developed. An essential aspect of the project was a
      targeted approach making use of multi-professional expertise and standards.
      METHODS: This 1-year feasibility study included a total of 58 patients with AE
      COPD in advanced age (mean: 74.8 +/- 6.8 years) with typical geriatric
      multimorbidity and necessity for acute medical as well as rehabilitation
      treatment. The results of the early geriatric rehabilitation by a multi
      professional rehabilitation team were analyzed in a prospective study approach
      using standardized assessments. RESULTS: The early geriatric rehabilitation
      started on median day 3 (range: 1st - 22nd) and lasted in median 16 days (range:
      9 - 29). It achieved a significant improvement, particularly in mobility [timed
      up-and-go, median 19 (range: 10 - 150) vs. 15 (range: 7 - 120) seconds, p <
      0.0001], self-help ability [Barthel index, median 73 (range: 5 - 95) vs. 95
      (range: 45 - 100) points, p < 0.0001] and social care. CONCLUSIONS: Early
      geriatric rehabilitation in a cohort of AE-COPD patients is feasible and can be
      integrated in an acute inpatient pulmonary care system.

PMID- 22477486
TI  - Two kinds of verbal behavior plus a possible third.
AB  - Speaking, writing, and signing (American Sign Language) are types of verbal
      behavior where each different verbal relation involves a different topography. It
      is also possible to behave verbally by pointing at or in some way indicating the
      relevant verbal stimuli, where response topographies do not differ from one
      verbal relation to another. There are a number of potentially important
      differences between topography-based and stimulus-selection-based verbal
      behavior, although the two are often treated as equivalent from a behavioral as
      well as from a traditional perspective. Selection-based verbal behavior involves
      a conditional discrimination whereas topography-based verbal behavior does not.
      In topography-based, but not in selection-based verbal behavior, there is point
      to-point correspondence between response form and relevant response product.
      Also, effective selection-based verbal behavior requires a good scanning
      repertoire whereas in topography-based verbal behavior the correct response
      simply becomes stronger under appropriate conditions. What is traditionally
      referred to as receptive language training is described as quite similar from a
      behavioral perspective to training in selection-based verbal behavior. Given the
      differences between topography- and selection-based verbal behavior, the wisdom
      of the current rather extensive reliance on selection-based verbal behavior in
      language instruction for developmentally disabled clients is seriously
      questioned.

PMID- 22477487
TI  - Studying the effects of the audience on verbal behavior.

PMID- 22477488
TI  - Teaching verbal behavior to pigeons.
AB  - Pigeons were taught simple analogs of verbal behavior by replicating and
      extending the procedures presented by Michael, Whitley, and Hesse (1983). A
      student lab, connected to a course on the experimental analysis of behavior, was
      used to teach both the students and the pigeons new behavioral repertoires. Most
      of the 18 birds learned a simple stimulus-selection-based tact, as well as 2-3
      topography-based tacts. Several pigeons learned to mand for reinforcers, and a
      few acquired some simple intraverbal responses. The student's learned the basic
      features of Skinner's analysis of verbal behavior, as well as several laboratory
      skills. Further work in this area is encouraged due to its potential
      contributions to the experimental analysis of verbal behavior, and to teaching
      language to the developmentally disabled, and other speech and language impaired
      individuals.

PMID- 22477489
TI  - The promotive: A verbal operant related to production.

PMID- 22477490
TI  - Verbal behavior: Child's talk.

PMID- 22477491
TI  - Notebooks by B. F. Skinner: A referenced index of entries relevant to verbal
      behavior.

PMID- 22477492
TI  - A response to Sundberg and Michael.

PMID- 22477493
TI  - Why are the intramyocardial portions of the coronary arteries spared from
      arteriosclerosis? Clinical implications.
AB  - Experienced cardiac surgeons are aware that the intramyocardial portions of the
      coronary arteries are rarely affected by arteriosclerosis. This is a striking and
      reliable finding in the operating room that is present even when the preceding
      and subsequent segments of the arteries are diseased. The present review
      describes the published evidence of embryological, anatomical and physiological
      differences between intramyocardial coronary arteries and their epicardial
      counterparts. Possible mechanisms of these differences are explored, and
      hypotheses are advanced as to how one may capitalize on these differences to
      provide better diagnosis and treatment of coronary artery disease. The absence of
      vasa vasorum in the intramyocardial coronary arteries appears to play a major
      role in their protection from arteriosclerosis. Fully understanding this peculiar
      phenomenon - the sparing of the intramyocardial coronary arteries - would be one
      giant step closer to unlocking the remaining mysteries of arteriosclerosis in
      general.

PMID- 22477494
TI  - Atherosclerosis in sickle cell disease - a review.
AB  - Acute, vaso-occlusive crises are the most common and earliest clinical
      manifestations of sickle cell disease. Recent thoughts about development of
      atherosclerosis as a result of this disease are presented. Current insights into
      the pathogenesis of atherosclerosis in sickle cell disease are reviewed, in
      particular the role of endothelial dysfunction, homocysteine and platelets.
      Common and uncommon sites of atherosclerosis are described. Radiological
      assessment and potential therapeutic agents to slow the progression of
      atherosclerosis are discussed. Finally, treatment of atherosclerosis in certain
      sites is evaluated and reviewed.

PMID- 22477495
TI  - Living donor renal transplant recipients tolerate early removal of bladder
      catheters.
AB  - Recipients of living donor renal grafts enjoy numerous benefits compared with
      deceased donor kidney recipients. Bladder catheterization allows for the
      continuous determination of urinary output and, theoretically, may prevent
      urinary leaks. A series of 25 consecutive renal transplants was reviewed to
      evaluate the timing of removal of bladder catheters after transplantation.
      Removing urinary catheters as early as 24 h to 48 h post-transplant showed no
      increase in undesirable outcomes. More than 50% of the patients had invasive
      bladder catheters in place for only one or two days. Early removal was associated
      with a lower rate of urinary tract infections, decreased length of
      hospitalization and possibly less discomfort, in the absence of detrimental
      effects.

PMID- 22477496
TI  - Cadaveric renal transplant recipients can safely tolerate removal of bladder
      catheters within 48 h of transplant.
AB  - The ideal time to remove urinary catheters after renal transplantation has not
      been thoroughly established. It remains unclear whether the anastomosis is
      actually protected with prolonged bladder catheterization. In addition, the
      incidence of urinary tract infections may increase with prolonged
      catheterization. A series of 57 consecutive deceased donor renal transplants was
      retrospectively reviewed for outcomes associated with duration of bladder
      catheterization. Removing urinary catheters within 48 h post-transplant showed no
      increase in undesirable outcomes, and very likely improved patient satisfaction.

PMID- 22477497
TI  - Access surgery for hemodialysis in the Cayman Islands: Preliminary results of a
      vascular access service.
AB  - OBJECTIVE: In the Cayman Islands, a vascular access service was created in 2005
      to facilitate the creation of vascular access for hemodialysis by local surgeons.
      The present retrospective audit aims to establish the outcomes of this practice
      in the Cayman Islands. METHODS: Data from the operative log of the Cayman Islands
      Hospital was collected over a period of 36 months. The data were analyzed using
      SPSS version 12.0 (SPSS Inc, USA). Statistical analyses were performed using
      Student's t tests and Fisher's exact tests. RESULTS: A total of 19 operative
      procedures were performed to create vascular accesses in 12 men and seven women.
      Thirteen procedures (68%) created autogenous arteriovenous fistulas (AVFs) and
      six (32%) involved the insertion of a prosthetic arteriovenous graft (AVG). There
      were six incident dialysis patients, all of whom had an AVF created. The
      remaining 13 prevalent dialysis patients had new accesses in the form of AVFs
      (n=7) or AVGs (n=6). The statistical analyses were limited by sample size, but
      with AVFs, there were trends toward reduced incidence of secondary failure (four
      of 13 versus four of six), thrombosis (four of 13 versus two of six), infectious
      morbidity (zero versus two of six) and less demand for interventions to maintain
      patency (one of 13 versus two of six) with AVFs. There were also trends toward
      superior primary (461 days versus 227 days) and secondary (803 days versus 205
      days) patency rates for AVFs. CONCLUSIONS: In this setting, the rate of AVF
      creation exceeds the goals set by the National Kidney Foundation Kidney Disease
      Outcomes Quality Initiative and the Fistula First Breakthrough Initiative. To
      ensure continued delivery of modern quality care, further audits of the local
      practice will be required at regular intervals.

PMID- 22477498
TI  - Endoluminal thermal ablation versus stripping of the saphenous vein: Meta
      analysis of recurrence of reflux.
AB  - BACKGROUND: Catheter-based minimally invasive techniques developed to treat
      saphenous vein insufficiency include endovenous laser and radiofrequency
      ablation. Their long-term results are under evaluation. A meta-analysis of trials
      was performed, comparing endovenous versus surgical saphenous vein ablation with
      focus on long-term (greater than 365 days) outcomes of recurrence of
      varicosities, reflux and symptomatic disease. METHODS: A systematic search of
      published studies reporting on the treatment of varicose veins was performed. The
      databases searched included Medline/PubMed, OVID, EMBASE, CINAHL,
      ClinicalTrials.gov, the Cochrane central register of controlled trials and the
      Cochrane database of systematic reviews. Search terms included saphenous vein
      ligation, stripping, radiofrequency ablation, laser ablation and endovenous
      ablation. Reports in all languages from 1966 to 2009 were considered. The
      'related articles' function was used to broaden the search. All article titles,
      abstracts and subject headings were screened by one reviewer for potential
      relevance. Abstracts of articles selected by title were read online to reduce the
      number of articles for full-text examination. Finally, additional titles were
      sought in the bibliographies of the retrieved articles. Only studies reporting
      outcomes after more than 365 days were selected. Analyzed outcomes included
      recurrence of varicosities and reflux, as documented by duplex ultrasound, and
      recurrence of signs and symptoms. Data extraction was performed from life tables,
      text or graphs. Statistical analysis was performed using the commercially
      available software CMA Version 2 (Biostat Inc, USA). The random effects model was
      used to calculate the ORs and 95% CIs. Statistical heterogeneity was evaluated
      using the Q value and considered present if P<0.05. RESULTS: Eight randomized
      controlled trials were included; these reported on 497 patients. Two hundred
      twenty-six patients underwent ligation and stripping and 271 underwent
      endoluminal thermal ablation. The mean (+/- SD) follow-up period was 584+/-182
      days. There was no difference in the age and sex distribution between the groups.
      There was no difference in the long-term recurrence rate between the two
      techniques (OR 0.97, 95% CI 0.48 to 1.9, P=0.9). Statistical heterogeneity was
      not significant (Q value P=0.5) and publication bias was limited. CONCLUSIONS:
      The analysis indicates that catheter-based treatments and traditional venous
      stripping with high ligation have similar long-term results. Establishing
      preoperative criteria for each method may improve outcomes but presently neither
      technique appears to confer an advantage in terms of mid- to long-term freedom
      from recurrent symptoms.

PMID- 22477499
TI  - The role of heart-type fatty acid-binding protein in the diagnosis of acute
      coronary syndrome.
AB  - BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a membrane-bound
      protein that facilitates transport of fatty acids from the blood into the heart.
      It is currently being used outside the United States for the early diagnosis of
      myocardial infarction (MI). However, previous studies have shown inconsistent
      correlation of H-FABP with standard cardiac biomarkers. METHODS: Fifty patients
      admitted with ST segment elevation MI (n=25), non-ST segment elevation MI (n=15)
      or unstable angina (n=10) were evaluated. The CardioDetect med cardiac infarction
      test (rennesens GmbH, Germany) was used to measure both qualitative and
      quantitative H-FABP. RESULTS: Of the 40 patients with acute MI, the initial
      troponin assay was positive in 35 patients (88%), the qualitative H-FABP assay
      was positive in 23 patients (58%) and the quantitative H-FABP assay was positive
      in 15 patients (38%) (P=0.001). No patient with MI had a positive H-FABP assay
      with a negative initial troponin assay. CONCLUSION: In the present study, the
      results of both the qualitative and quantitative H-FABP assays neither appeared
      earlier nor provided increased sensitivity compared with troponin in diagnosing
      acute MI. Accordingly, the use of H-FABP as a diagnostic tool for MI is limited.

PMID- 22477500
TI  - Should symptomatic, isolated distal deep vein thrombosis be treated with
      anticoagulation?
AB  - BACKGROUND: During the past two decades, the diagnosis of deep venous thrombosis
      (DVT) has made considerable progress. The term distal or calf vein thrombosis
      includes thrombosis in infrapopliteal veins, including the posterior tibial,
      peroneal, anterior tibial and muscular calf veins. The necessity of treating of
      distal DVT is debatable. OBJECTIVE: To determine whether treatment of isolated,
      distal DVT with anticoagulation versus no treatment affects patient outcome.
      METHODS: All patients discharged with a diagnosis of distal DVT from Tan Tock
      Seng Hospital, Singapore, between January 1, 2006, and December 31, 2007, were
      identified by the medical records office of the hospital. Compression of the
      intraluminal thrombus by duplex scan was used to diagnose distal DVT. Excluded
      were patients who either had both distal and proximal DVT, or had distal DVT
      along with pulmonary embolism (PE) at presentation. Complete resolution of distal
      DVT on repeat duplex scan was used to measure the primary outcome. Repeat follow
      up scans were performed at two weeks, one month, three months and six months, or
      on subsequent follow-up until the distal DVT had resolved completely. Secondary
      outcome measures were complete improvement of symptoms, progression of
      thrombosis, or PE or death during the follow-up period. The study included 68
      patients with distal DVT; however, 17 patients with PE, two of whom had proximal
      DVT (in the iliac and common femoral veins) at the first presentation along with
      distal DVT, were excluded from the study. In total, 51 patients were included for
      analysis. The follow-up scan was available in 35 patients; therefore, the primary
      analysis was performed in 35 patients (47 incidences of distal DVT). However, the
      secondary analysis was available in all 51 patients. Of the 35 patients available
      for follow-up scans, 17 patients (25 incidences of distal DVT) received
      anticoagulation and 18 patients (22 incidences of distal DVT) received no
      anticoagulation. Of the 17 patients who were treated with anticoagulation, nine
      patients (13 incidences of distal DVT) received enoxaparin at a dose of 1 mg/kg
      twice a day for two weeks and eight patients (12 incidences of distal DVT)
      received warfarin for a period of three months with initial overlap of enoxaparin
      1 mg/kg twice a day for three to five days. Once the prothrombin time
      international normalized ratio of a patient on warfarin was between 2 and 3,
      enoxaparin was discontinued. The 18 patients who did not receive anticoagulation
      received follow-up with regular duplex scan. RESULTS: There were no statistically
      significant differences among the groups in the resolution of distal DVT or
      symptom improvement with or without treatment. In the group that received no
      treatment, one death occurred. Proximal extension and PE were not recorded in any
      of the patients. CONCLUSION: Distal DVT may not require treatment with
      anticoagulation. If leg symptoms worsen, or if there is an extension of distal
      DVT on the follow-up scan, treatment with anticoagulation is recommended.

PMID- 22477501
TI  - Vitamin E does not slow the progression of hypercholesterolemic atherosclerosis.
AB  - BACKGROUND: Vitamin E suppresses the development of atherosclerosis but does not
      regress established hypercholesterolemic atherosclerosis. OBJECTIVES: To
      investigate whether vitamin E slows the progression of established
      atherosclerosis, and whether this effect is associated with reductions in serum
      lipids and oxidative stress. METHODS: THE PRESENT STUDY WAS PERFORMED IN FOUR
      GROUPS OF RABBITS: group I, regular diet (control); group II, 0.25% cholesterol
      diet (two months); group III, 0.25% cholesterol diet (four months); and group IV,
      0.25% cholesterol diet (two months) followed by 0.25% cholesterol and vitamin E
      (two months). Serum lipids and the chemiluminescent activity of white blood cells
      (WBC-CL), a measure of oxygen radical production by white blood cells, were
      measured before and at monthly intervals for the duration of the study. Aortas
      were removed at the end of the protocol for assessment of atherosclerosis and the
      chemiluminescent activity of aortic tissue (aortic-CL), a measure of antioxidant
      reserve. RESULTS: Atherosclerosis was associated with hyperlipidemia and
      increased oxidative stress, indicated by increased nonactivated WBC-CL and
      alteration of the aortic-CL. Significant areas of the intimal surfaces of the
      aortas from group II (26.54%+/-4.11%), group III (69.37%+/-5.34%) and group IV
      (65.96%+/-7.86%) were covered with atherosclerotic lesions. Vitamin E did not
      alter serum lipids, aortic antioxidant reserve or WBC-CL. Vitamin E was
      ineffective in slowing the progression of hypercholesterolemic atherosclerosis.
      CONCLUSION: Vitamin E did not slow the progression of hypercholesterolemic
      atherosclerosis, and this effect was associated with its ineffectiveness in
      reducing serum lipids and oxidative stress.

PMID- 22477502
TI  - Celiac artery embolism due to thrombophilia - a case report.
AB  - A case of celiac artery embolism in a patient with factor V Leiden thrombophilia
      is reported. The embolism was likely due to an undetected cardiac thrombus,
      causing an abdominal aortic embolism. The patient underwent emergency surgery for
      the abdominal embolism. The celiac artery embolism was treated nonsurgically due
      to the presence of collateral circulation through the gastroduodenal artery from
      the superior mesenteric artery. The patient fully recovered and was discharged
      from the hospital one month after his first referral.

PMID- 22477503
TI  - New fibrillin gene mutation - possible cause of ascending aortic dilation in
      patients with aortic valve disease: Preliminary results.
AB  - BACKGROUND: Approximately 10% of patients who undergo surgery for aortic valve
      disease (stenosis or regurgitation) suffer from ascending aortic dilation (AAD).
      A possible genetic etiology of AAD associated with aortic valve disease has been
      repeatedly mentioned in the literature, but a specific responsible gene mutation
      has not been described. METHODS: In the present study, two groups of patients
      were compared, all of whom underwent surgery for aortic valve disease. Group A
      was a cohort of 27 patients who suffered from aortic valve disease associated
      with AAD. Group B was a cohort of 29 patients with structural aortic valve
      disease, but without concomitant AAD (control group). Genomic DNA was extracted
      from the white blood cells of peripheral blood samples and was amplified using
      primers specific for chosen exons of the fibrillin-1 gene, including their
      intron/exon boundaries. Exons 26 and 27 were selected for analysis. RESULTS:
      Analysis of the intronic part situated close to exon 27 showed insertion of
      cytosine between nucleotide 37 682 and 37 683 of query sequence. This insertions
      was classified as IVS 37 682 and 37 683insC. This mutation was found in all 27
      patients from group A (patients with structural aortic valve disease accompanied
      by significant AAD). The abovementioned mutation was not found in any of the 29
      patients from group B. CONCLUSIONS: This finding has potential implications for
      risk stratification and therapeutic targeting not only for patients with existing
      disease, but also for the general population. Future studies are needed to
      determine the clinical utility of the finding; however, the present hypothesis
      needs to be verified by further molecular studies.

PMID- 22477504
TI  - On the difference between verbal and nonverbal behavior.
AB  - Language theorists have often proposed lists of the defining properties of
      language. This account reviews some of these and offers as an alternative a three
      item list consisting of instructional control, equivalence classes, and
      autoclitic processes.

PMID- 22477505
TI  - Repertoire-altering effects of remote contingencies.

PMID- 22477506
TI  - Post-session verbal reports and the experimental analysis of behavior.
AB  - Experimental analyses of the performance of verbal subjects often include verbal
      reports, obtained during post-session interviews, about within-session covert
      verbal behavior (e.g., hypotheses about the contingencies). But such post-session
      reports are not necessarily accurate, and procedural details of how the samples
      were obtained are typically inadequate. Even when the post-session reports are
      accurate, the within-session hypotheses do not have the status of causes of
      within-session nonverbal performance. In an experimental analysis, it is
      important to treat such reports as instances, not causes, of behavior.

PMID- 22477507
TI  - Psychological linguistics: A natural science approach to the study of language
      interactions.
AB  - Kantor's theoretical analysis of "psychological linguistics" offers a natural
      science approach to the study of linguistic behavior and interactions. This paper
      includes brief descriptions of (a) some of the basic assumptions of the approach,
      (b) Kantor's conception of linguistic behavior and interactions, (c) a compatible
      research method and sample research data, and (d) some areas of research and
      application.

PMID- 22477508
TI  - Dysfunctional control by client verbal behavior: The context of reason-giving.
AB  - Dysfunctional control exerted by reason-giving in adult psychopathology is
      interpreted from a radical behavioral perspective. Verbal-social contingencies
      which support the establishment of reason-giving and its control over maladaptive
      actions are reviewed. A contextual approach to psychotherapy, comprehensive
      distancing, which attempts to weaken dysfunctional verbal control is described
      briefly. Data relevant to therapeutic process are presented. The overall results
      suggest that comprehensive distancing facilitates therapeutic change through a
      process consistent with a behavioral analysis of reason-giving. Suggestions for
      further research and radical behavioral approaches to psychotherapy are
      discussed.

PMID- 22477509
TI  - Reference citations in B. F. Skinner's verbal behavior.

PMID- 22477510
TI  - Polyphenols are medicine: Is it time to prescribe red wine for our patients?
AB  - Alcohol, specifically red wine, has been suggested to play a key role in the
      prevention of cardiovascular disease and other chronic pathologies, including
      cancer. Its regular and moderate consumption has been found in numerous
      epidemiological studies to correlate inversely with vascular disease and
      mortality, despite the presence of risk factors such as high consumption of
      saturated fats, elevated smoking and low physical activity. This phenomenon,
      known as the 'French Paradox', would be explained mainly by the high levels of
      polyphenols present in red wine, making it more advantageous than beer, spirits
      and even white wine. The habit of having one or two drinks of red wine every day
      with meals may translate to a longer, healthier and better quality of life.

PMID- 22477512
TI  - Long-term outcome of infrapopliteal catheter-based intervention for critical limb
      ischemia.
AB  - CONTEXT: Percutaneous treatment of tibioperoneal occlusive disease is associated
      with decreased morbidity compared with bypass surgery. The long-term patency and
      limb salvage rates are not well documented. AIMS: To evaluate the long-term
      outcome of endoluminal interventions for tibioperoneal lesions. METHODS: A
      retrospective study was performed to determine the outcomes of patients
      undergoing infrapopliteal catheter-based intervention for critical limb ischemia.
      Collected data included demographics, comorbidities, clinical presentation, pre-
      and postintervention noninvasive vascular measurements (segmental pressure and
      waveforms, and ankle-brachial index [ABI]), type of intervention, limb loss rate,
      patient follow-up and need for surgical revascularization. Statistical analysis
      was performed with the two-tailed t test. P<0.05 was considered significant;
      results were reported as mean +/- SD. Cox regression analysis and Kaplan-Meier
      limb survival analysis were performed to demonstrate freedom from amputation over
      time. RESULTS: Thirty-five patients underwent intervention from 2003 to 2008;
      technical success was achieved in 26 patients (75%). Arterial segmental pressure
      studies revealed a significant increase in ABI - preprocedure ABI was 0.62+/-0.24
      versus a postintervention ABI of 0.81+/-0.29 (P=0.02). The limb salvage rate was
      63% during the follow-up period. Limb salvage was better for patients who
      underwent isolated infrapopliteal intervention versus combined above and below
      the knee intervention. CONCLUSION: Percutaneous interventions for tibioperoneal
      occlusive disease offer an acceptable limb salvage rate and may be the preferred
      initial treatment for critical limb ischemia.

PMID- 22477511
TI  - Etiopathogenesis, clinical diagnosis and treatment of thromboangiitis obliterans 
      current practices.
AB  - Thromboangiitis obliterans (TAO) is a segmental inflammatory occlusive disorder
      that affects small- and medium-sized arteries, and arm and leg veins of young
      smokers. Several different diagnostic criteria have been offered for the
      diagnosis of TAO. Clinically, it manifests as migratory thrombophlebitis or signs
      of arterial insufficiency in the extremities. It is characterized by highly
      cellular and inflammatory occlusive thrombi, primarily of the distal extremities.
      Thromboses are often occlusive and sometimes display moderate, nonspecific
      inflammatory infiltrate, consisting mostly of polymorphonuclear leukocytes,
      mononuclear cells and rare multinuclear giant cells. The immune system appears to
      play a critical role in the etiology of TAO. However, knowledge about
      immunological aspects involved in the progression of vascular tissue
      inflammation, and consequently, the evolution of this disease, is still limited.
      There are several studies that suggest the involvement of genetic factors and
      results have shown increasing levels of antiendothelial cell antibodies in
      patients with active disease. Vasodilation is impaired in patients with TAO. TAO
      disorder may actually be an autoimmune disorder, probably initiated by an unknown
      antigen in the vascular endothelium, possibly a component of nicotine. There are
      various therapies available for treatment of TAO, but the major and indispensable
      measure is smoking cessation. Except for discontinuation of tobacco use, no forms
      of therapy are definitive. Sympathectomy, cilostazol and prostaglandin analogues
      (prostacyclin or prostaglandin E) have been used in specific conditions.
      Recently, therapeutic angiogenesis with autologous transplantation of bone marrow
      mononuclear cells has been studied in patients with critical limb ischemia.

PMID- 22477513
TI  - Selective two-stage basilic and cephalic vein transpositions can significantly
      improve the rate of fistula construction.
AB  - INTRODUCTION: Modified proximal radial artery arteriovenous fistula (MPRAVF) can
      be used to improve the success and patency of basilic vein transposition (BVT)
      and cephalic vein transposition (CVT). In the present study, surgical experience
      with patients requiring a two-stage BVT or CVT using MPRAVF as the first stage
      was reviewed. METHODS: All two-stage BVTs and CVTs performed between September
      2004 and October 2006 were retrospectively reviewed. The median follow-up for
      this cohort was 23.7 months. One-year secondary patency of all transpositions was
      assessed. RESULTS: Two hundred nineteen MPRAVFs were constructed. Twelve MPRAVFs
      failed and underwent a second procedure. Ninety-eight patients required no
      further procedures and their upper arm cephalic vein was matured and used for
      dialysis. Of 121 patients whose MPRAVFs were functioning but unusable due to
      their depth, 87 underwent BVT and 34 underwent CVT. The Kaplan-Meier one-year
      secondary patencies (+/- standard error) for BVTs and CVTs were 0.90+/-0.03 and
      0.82+/-0.06, respectively. At one year, 87% of all transpositions remained
      patent. CONCLUSIONS: Use of MPRAVF as the first stage of a two-stage BVT or CVT
      can significantly improve the patency rate of autogenous hemodialysis access
      placement beyond the 66% set forth by the Fistula First guidelines.

PMID- 22477514
TI  - Operative management of multilevel iliofemoral occlusive disease.
AB  - BACKGROUND: The current trend is to treat both inflow and outflow occlusive
      disease using endovascular procedures either simultaneously or in a staged
      procedure. The long-term benefits of a combined one-stage approach are not
      available. OBJECTIVES: The main objectives are to investigate the risks and long
      term benefits of a combined one-stage approach using endovascular techniques for
      iliac occlusive disease and bypass for femoropopliteal occlusive disease. METHODS
      AND RESULTS: Fifty-three patients with limb ischemia underwent combined ilial
      stenting and distal bypass. Complications included minor wound problems in nine
      patients, atrial fibrillations in one patient, acute graft occlusion in one
      patient, toe amputation in two patients and one death. During a follow-up period
      of up to 96 months, eight patients required repeat distal bypass, five patients
      underwent revascularization on contralateral sides and four patients had repeat
      endovascular procedures. CONCLUSION: These results suggest that there are few
      risks with a combined endovascular procedure for iliac occlusion and bypass for
      femoropopliteal occlusive disease. Long-term complications with the combined
      approach included repeat distal bypass, revascularization on contralateral sides
      and repeat endovascular procedure.

PMID- 22477515
TI  - Suprarenal stricture of the inferior vena cava with massive iliocaval and distal
      thromboses successfully treated with catheter-directed thrombectomy, thrombolysis
      and angioplasty.
AB  - Long-term complications from deep vein thrombosis, such as post-thrombotic
      syndrome and chronic venous insufficiency, can result in significant morbidity
      for the affected patient. Although anticoagulation has been the conventional
      method of treatment, the benefit of thrombus burden removal cannot be
      underestimated. The present case report describes the successful treatment of
      extensive iliocaval and distal thrombosis with suprarenal inferior vena cava
      stricture using catheter-directed thrombolysis, thrombectomy and angioplasty.

PMID- 22477516
TI  - Aortic dissection after open repair of an infrarenal aortic aneurysm.
AB  - INTRODUCTION: A case of thoracic-abdominal dissection after open surgical
      exclusion of an infrarenal aortic aneurysm is presented. CASE PRESENTATION: A 62
      year-old woman was diagnosed with an infrarenal abdominal aortic aneurysm with a
      rapid increase in maximal diameter. She underwent surgery for aneurysm exclusion
      by an end-to-end aortoaortic bypass with Dacron collagen (Intervascular; WL Gore
      & Associates Inc, USA). After 15 days, she was admitted to the emergency
      department with intense epigastric and lumbar pain. Computed tomography
      angiography with contrast revealed an aortic dissection with origin in the
      proximal bypass anastomosis and cranial extension to the thoracic aorta. The true
      lumen at the level of the eighth thoracic vertebra was practically collapsed by
      the false lumen. The celiac trunk, and the mesenteric and renal arteries were
      perfused by the true lumen. After the acute phase of the aortic dissection,
      surgical repair was planned. Two paths of false lumen were found - one at the
      thoracic aorta and the second in the proximal bypass anastomosis. Surgical repair
      comprised two approaches. First, a Valiant Thoracic stent graft (Medtronic Inc,
      UK) was implanted distal from the left subclavian artery, expanding the collapsed
      true lumen and covering the false and dissected lumen. Second, an infrarenal
      Endurant abdominal stent graft (Medtronic Inc) was implanted. This second device
      was complemented with an aortic infrarenal extension using a Talent abdominal
      stent graft (Medtronic Inc) in the infrarenal aortic neck to achieve a hermetic
      seal. The postoperative clinical course was uneventful, and her symptoms were
      completely resolved in six months. CONCLUSION: Arteritis must be taken into
      account in young patients with high inflammatory markers. Covered stents and
      endoprosthetic devices seem to be effective methods to seal the dissected lumen.

PMID- 22477517
TI  - Deep venous thrombosis caused by congenital inferior vena cava agenesis and
      heterozygous factor V Leiden mutation - a case report.
AB  - The unusual clinical presentation, importance of imaging techniques and role of
      low molecular weight heparin are described for an initial treatment of thrombosis
      in inferior vena cava agenesis associated with heterozygous factor V Leiden. The
      patient, a 36-year-old woman, presented to the emergency room with sudden onset
      of back pain, swelling of the legs and thighs, and claudication while walking.
      Abdominal ultrasonography was immediately ordered. Anomalies in vascular blood
      flow were detected. Computed tomography was performed, and initially showed a
      complete absence of the infrarenal segment of inferior vena cava caudally to the
      origin of both renal veins. Treatment with enoxaparin (1 mg/kg twice per day) was
      started. The patient was discharged and returned to her activities of daily
      living two weeks after admission. This vascular abnormality is mostly
      incidentally diagnosed in adults and only a few cases are described as being
      associated with thrombophilia.

PMID- 22477519
TI  - Abstracts of the 5(th) Cachexia Conference, Barcelona, Spain, December 5-8, 2009.

PMID- 22477518
TI  - Percutaneous treatment of spontaneous left main coronary artery dissection
      extending to the left anterior descending and circumflex arteries possibly
      triggered by thrombolytic therapy.
AB  - Spontaneous coronary artery dissection is a rare cause of myocardial infarction
      and the role of thrombolytic therapy in this setting is not known. A case of
      acute ST elevation myocardial infarction is presented, with initial positive
      response to thrombolytic therapy and subsequent marked worsening of ST elevation
      due to extensive dissection, possibly triggered by thrombolytic therapy, which
      was successfully treated with percutaneous coronary intervention.

PMID- 22477520
TI  - Inflammatory rheumatic disorders and bone.
AB  - Inflammatory joint diseases such as rheumatoid arthritis, as well as other
      rheumatic conditions, such as systemic lupus erythematosus (SLE) and ankylosing
      spondylitis, comprise a heterogeneous group of joint disorders that are all
      associated with extra-articular side effects, including bone loss and fractures.
      The concept of osteoimmunology is based on growing insights into the links
      between the immune system and bone. The pathogenesis of osteoporosis in these
      patients is multifactorial. We have, more or less as an example, described this
      extensively for patients with SLE. High disease activity (inflammation) and
      immobility are common factors that substantially increase fracture risk in these
      patients, on top of the background fracture risk based on, among other factors,
      age, body mass index, and gender. Although no fracture reduction has been shown
      in intervention studies in patients with inflammatory rheumatic diseases, we
      present treatment options that might be useful for clinicians who are treating
      these patients.

PMID- 22477521
TI  - The immune system in the aging human.
AB  - With the improvement of medical care and hygienic conditions, there has been a
      tremendous increment in human lifespan. However, many of the elderly (>65 years)
      display chronic illnesses, and a majority requires frequent and longer
      hospitalization. The robustness of the immune system to eliminate or control
      infections is often eroded with advancing age. Nevertheless, some elderly
      individuals do cope better than others. The origin of these inter-individual
      differences may come from genetic, lifestyle conditions (nutrition, socio
      economic parameters), as well as the type, number and recurrence of pathogens
      encountered during life. The theory we are supporting is that chronic infections,
      through life, will induce profound changes in the immune system probably due to
      unbalanced inflammatory profiles. Persistent viruses such a cytomegalovirus are
      not eliminated and are a driven force to immune exhaustion. Because of their age,
      elderly individuals may have seen more of these chronic stimulators and have
      experienced more reactivation episodes ultimately leading to shrinkage of their
      repertoire and overall immune robustness. This review integrates updates on
      immunity with advancing age and its impact on associated clinical conditions.

PMID- 22477522
TI  - Regulation of frontline antibody responses by innate immune signals.
AB  - Mature B cells generate protective immunity by undergoing immunoglobulin (Ig)
      class switching and somatic hypermutation, two Ig gene-diversifying processes
      that usually require cognate interactions with T cells that express CD40 ligand.
      This T-cell-dependent pathway provides immunological memory but is relatively
      slow to occur. Thus, it must be integrated with a faster, T-cell-independent
      pathway for B-cell activation through CD40 ligand-like molecules that are
      released by innate immune cells in response to microbial products. Here, we
      discuss recent advances in our understanding of the interplay between the innate
      immune system and B cells, particularly "frontline" B cells located in the
      marginal zone of the spleen and in the intestine.

PMID- 22477523
TI  - Human B cell defects in perspective.
AB  - While primary immune defects are generally considered to lead to severe and
      easily recognized disease in infants and children, a number of genetic defects
      impairing B cell function may not be clinically apparent or diagnosed until adult
      life. The commonest of these is common variable immune deficiency, the genetic
      origins of which are beginning to be at least partially understood. CVID affects
      ~ 1/25,000 Caucasians and is characterized by a marked reduction in serum IgG,
      almost always in serum IgA, and reduced serum IgM in about half of all cases;
      these defects continue to provide an opportunity to investigate the genes
      necessary for B cell function in humans. Recently, a small number of genes
      necessary for normal B cell function have been identified in consanguineous
      families leading to varying degrees of hypogammaglobulinemia and loss of antibody
      production. In other studies, whole-exome sequencing and copy number variation,
      applied to large cohorts, have extended research into understanding both the
      genetic basis of this syndrome and the clinical phenotypes of CVID.

PMID- 22477524
TI  - HPK1 as a novel target for cancer immunotherapy.
AB  - Identifying the appropriate drug targets for the development of a novel anti
      tumor immunotherapy is one of the most risky steps in the drug development cycle.
      We have identified a hematopoietic cell-restricted serine/threonine kinase,
      hematopoietic progenitor kinase 1 (HPK1), as a possible target for therapeutic
      intervention. Targeted disruption of HPK1 alleles confers T cells with an
      elevated Th1 cytokine production in response to TCR engagement. HPK1 (-/-) T
      cells proliferate more rapidly than the haplotype-matched wild-type counterpart
      and are resistant to prostaglandin E2 (PGE(2))-mediated suppression. Most
      strikingly, mice that received adoptive transfer of HPK1 (-/-) T cells became
      resistant to lung tumor growth. Also, the loss of HPK1 from dendritic cells (DCs)
      endows them with superior antigen presentation ability, enabling HPK1 (-/-) DCs
      to elicit a more potent anti-tumor immune response when used as cancer vaccine.
      It is probable that blocking the HPK1 kinase activity with a small molecule
      inhibitor may activate the superior anti-tumor activity of both cell types,
      resulting in a synergistic amplification of anti-tumor potential. Given that HPK1
      is not expressed in any major organs, it is less likely that an inhibitor of HPK1
      kinase activity would cause any serious side effects.

PMID- 22477525
TI  - NFkappaB and ubiquitination: partners in disarming RIPK1-mediated cell death.
AB  - The mechanisms regulating cell survival and thus its corollary, cell death, have
      been intensively studied over the last two decades. Recent studies have shed new
      light into how non-degradative ubiquitination of the kinase RIPK1 is critical in
      determining this cell fate. In this review, we summarize recent findings on how
      ubiquitination of RIPK1 constitutes a survival signal through both NFkappaB
      independent and NFkappaB-dependent mechanisms. However, in the absence of
      ubiquitination, RIPK1 becomes a death-signaling molecule capable of engaging both
      the caspase-dependent apoptosis machinery and the recently described RIPK3
      dependent necroptosis machinery. Another layer of complexity is now emerging in
      that components of the ubiquitin-modifying machinery are themselves regulated by
      proteolytic processing. This survival/death regulatory mechanism has been best
      analyzed in the context of TNF receptor signaling, but it is likely that
      principles learned from TNFR may be applicable to other immune receptors
      including the antigen and Toll-like receptors.

PMID- 22477526
TI  - Biology of autoreactive extrathymic T cells and B-1 cells of the innate immune
      system.
AB  - Cumulative evidence has shown that extrathymic T cells can be autoreactive and
      that B-1 cells may produce autoantibodies. These T and B-1 cells, which form part
      of the innate immune system, tend to be activated simultaneously when
      conventional T and B cells are in a suppressive state, for example, when thymic
      atrophy occurs by stress or involution with aging. In other words, autoreactive T
      cells and autoantibody-producing B cells are different from thymus-derived T
      cells and bone marrow-derived B cells. Activated extrathymic T cells and B-1
      cells are often observed in numerous autoimmune diseases, aging, malarial
      infection and chronic graft-versus-host disease. It is thought that the
      autoreactivity of extrathymic T cells and B-1 cells may be important for the
      elimination of "abnormal self" tissues or cells. However, over-activation of
      innate lymphocytes may be related to the onset of disease or self-tissue
      destruction. However, it must be emphasized that the autoreactivity of innate
      lymphocytes is not generated by failure of the thymic pathway of T-cell
      differentiation or the conventional pathway of B-2 cells.

PMID- 22477527
TI  - Complement regulation of T cell immunity.
AB  - Results of studies published since 2002 reveal that T cells and antigen
      presenting cells (APCs) produce complement proteins. The immune cell-derived,
      alternative pathway complement components activate spontaneously, yielding local,
      but not systemic, production of C3a and C5a. These anaphylatoxins bind to their
      respective G-protein-coupled receptors, C3aR and C5aR, expressed on both
      partners. The resultant complement-induced T cell activation and APC activation
      drive T cell differentiation, expansion and survival. Complement deficiency or
      blockade attenuates T cell-mediated autoimmunity and delays allograft rejection
      in mice. Increasing complement activation, achieved by genetic removal of the
      complement regulatory protein decay-accelerating factor, enhances murine T cell
      immunity and accelerates allograft rejection. The findings support the need for
      design and testing of complement inhibitors in humans.

PMID- 22477529
TI  - Some contingencies of spelling.
AB  - This paper presents some speculation about the contingencies that might select
      standard spellings. The speculation is based on a new development in the teaching
      of spelling-the process writing approach, which lets standard spellings emerge
      collateral to a high frequency of reading and writing. The paper discusses this
      approach, contrasts it with behavior-analytic research on spelling, and suggests
      some new directions for this latter research based on a behavioral interpretation
      of the process writing approach to spelling.

PMID- 22477528
TI  - Antitumor efficacy of viable tumor vaccine modified by heterogenetic ESAT-6
      antigen and cytokine IL-21 in melanomatous mouse.
AB  - The goal of this study was to investigate whether glycosylphosphatidylinositol
      (GPI)-anchored 6 kDa early secreted antigenic target (ESAT-6) and IL-21-producing
      B16F10/ESAT-6-GPI-IL-21 viable vaccine would induce antitumor efficacy. Mice were
      immunized with B16F10/ESAT-6-GPI-IL-21 vaccine and challenged by B16F10 cells 2
      weeks later. Antitumor efficacy and mechanisms of the vaccine were analyzed.
      Vaccination with the viable B16F10/ESAT-6-GPI-IL-21 vaccine resulted in an
      increase of IFN-gamma level and the CD8(+)CTL cytotoxicity, a decrease in TGF
      beta generation and increase in the expression of miR-200c that serves as
      melanoma suppressor by directly targeting zinc-finger E-box binding homeobox 1 to
      inhibit epithelial-mesenchymal transition and block tumor metastasis. The vaccine
      significantly inhibited the melanoma growth, reduced the lung melanoma nodules,
      and prolonged the mouse survival compared with the controls. These findings
      highlighted IL-21 as an immune adjuvant in an engineered viable tumor vaccine to
      reinforce heterogenetic antigen ESAT-6 immune tolerance break to induce powerful
      antitumor efficacy in mice.

PMID- 22477530
TI  - Generative strategies and teaching for generalization.

PMID- 22477531
TI  - Rules as environmental events.

PMID- 22477532
TI  - Rule-following and human operant responding: Conceptual and methodological
      considerations.
AB  - A conceptual analysis of rule-governed behavior, emphasizing pliance and tracking
      as functional classes of rule-following, is provided and related to previous
      methodological strategies in human operant research. A novel strategy, which
      utilizes a microcomputer to reinforce correspondences between subject guesses and
      responding, is proposed for the study of rule-following. Results from a
      preliminary demonstration of the procedures are reported briefly, and possible
      applications to the further analysis of rule-following are discussed.

PMID- 22477533
TI  - Teaching mands by manipulating conditioned establishing operations.
AB  - Skinner's (1957) analysis of verbal behavior suggests the functional independence
      of the verbal operants. However, only a few empirical studies have directly
      examined the nature of these operants, and their independence. The present study
      evaluated whether teaching topographies as tacts would lead to their emission as
      mands. The results indicated that manding only occurred reliably after direct
      mand training, which consisted of the use of imitative and tact prompts, and
      fading those prompts, to transfer stimulus control from nonverbal stimuli to
      conditioned establishing operations. The results contribute to the existing data
      on the functional independence of mands and tacts, as well as demonstrate the
      value of manipulating conditioned establishing operations for mand training.

PMID- 22477534
TI  - The effects of alternating mand and tact training on the acquisition of tacts.
AB  - Two training procedures were compared with respect to the average number of
      training trials it took to teach new verbal responses to normal children. Mand
      contingencies were alternated with tact contingencies in one condition while only
      tact contingencies were in effect in the other condition. Normal, preschool
      children served as subjects and toy parts were the objects that were to be named.
      The results indicated that it took, on the average, fewer trials to teach part
      names (tacts) in the mand-tact condition than in the tact only condition.
      Although more research is needed to confirm this, it appears that mand
      contingencies involve stronger controlling variables and can facilitate the
      acquisition of a tact repertoire.

PMID- 22477535
TI  - A description of the verbal behavior of students during two reading instruction
      methods.
AB  - The responses of students during two reading methods, the language experience
      approach and two Mastery Learning programs, were analyzed using verbal operants.
      A description of student responding was generated for these methods. The purpose
      of the study was to answer the questions: What are the major controlling
      variables determining student reading behavior during the language experience
      approach and two Mastery Learning programs, and how do these controlling
      variables change across story reading sessions and across stories in the first
      method? Student responses by verbal operant were compared for both reading
      methods. Findings indicated higher frequencies of textual operants occurred in
      responses during the Mastery Learning programs. A greater reliance on intraverbal
      control was evident in responses during the language experience approach. It is
      suggested that students who can generate strong intraverbal responses and who may
      have visual discrimination problems during early reading instruction may benefit
      from use of the language experience approach at this stage.

PMID- 22477536
TI  - On diversity in the terminology concerning inhibitory stimulus control:
      Implications for practitioners of applied behavior analysis.
AB  - The multiplicity of terms employed in the literature of behavior analysis to tact
      stimuli associated with inhibition effects is considered. It is submitted that
      whereas there is diversity in the conditioning histories associated with
      inhibitory stimulus control, there is commonality in the controlling properties
      invested in contiguous stimuli by those various histories. The author contends
      that there is heuristic value in organizing the scientific language of behavior
      analysts on this topic around inhibition as a process. It is further suggested
      that the many tacts for inhibition-related stimuli, divided as they are along
      what might be called procedural lines, distract from what is argued here to be
      the core operation, viz., stimulus mediated inhibition.

PMID- 22477537
TI  - A novel delta-globin gene mutation (HBD: c.323G>A) masking the diagnosis of beta
      thalassemia: a first report from India.
AB  - An elevated HbA(2) (alpha2delta2) level (>3.5%) is a well-established diagnostic
      test for heterozygous beta-thalassemia. Mutations in the delta-globin gene can
      cause decreased expression of HbA(2), resulting in heterozygous beta-thalassemia
      with normal levels of HbA(2). In this report, we describe a novel missense
      mutation in delta-globin (HBD: c.323G>A, Gly > Asp) in an Indian family with
      heterozygous beta-thalassemia with normal HbA(2) levels.

PMID- 22477539
TI  - Guest editorial: Current understanding of thrombosis and hemostasis--from bench
      to bedside.

PMID- 22477538
TI  - von Willebrand factor: at the crossroads of bleeding and thrombosis.
AB  - Hemostasis and thrombosis represent two sides of the same coin. Hemostasis
      maintains blood fluidity in the vascular system while allowing for rapid thrombus
      formation to prevent excessive hemorrhage after blood vessel injury. Thrombosis
      is a pathologic extension of the normal hemostatic mechanism, occurring when
      unwanted clot formation develops in certain pathological situations. The
      molecular mechanisms underlying both phenomena are fundamentally identical. One
      of the key players in both processes is the plasma glycoprotein von Willebrand
      factor, which perfectly illustrates this duality between hemostatic and
      thrombotic mechanisms. The purpose of this review is to discuss novel findings on
      the role of von Willebrand factor at this interface, and how some of these
      findings may help develop new therapeutic strategies.

PMID- 22477540
TI  - Polyphosphate: a link between platelets, coagulation and inflammation.
AB  - Inorganic polyphosphate (polyP) is abundant in biological organisms. PolyP is a
      major component of dense granules of human platelets and is secreted upon
      platelet activation. Studies from our lab and others have shown that polyP is a
      potent modulator of the blood clotting cascade, acting as a pro-hemostatic,
      prothrombotic and proinflammatory agent depending on its polymer size and
      location. PolyP may represent at least one of the long-sought (patho)physiologic
      activators of the contact pathway of blood clotting, and its actions may also
      help to explain previously unexplained abilities of activated platelets to
      enhance plasma clotting reactions. PolyP may have utility as a hemostatic agent
      to control bleeding, and conversely, polyP antagonists might have utility as
      antithrombotic/anti-inflammatory agents with reduced bleeding side effects. The
      detailed molecular mechanisms by which polyP modulates blood clotting reactions
      still remain to be elucidated.

PMID- 22477542
TI  - Factor XIII is a key molecule at the intersection of coagulation and fibrinolysis
      as well as inflammation and infection control.
AB  - Factor XIII (FXIII) is a transglutaminase consisting of two catalytic A subunits
      (FXIII-A) and two non-catalytic B subunits (FXIII-B) in plasma. FXIII-B protects
      FXIII-A from its clearance. FXIII-A is also present as a homodimer inside
      megakaryocytes/platelets and monocytes/macrophages. Although possible functions
      of intracellular FXIII-A have been proposed, these remain to be established.
      Intra- and extra-cellular FXIIIs support platelet adhesion and spreading as well
      as clot retraction, suggesting that FXIII is important for the stabilization of
      platelet-fibrin clots. Intra- and extra-cellular FXIIIs also support
      immobilization and killing of bacteria as well as phagocytosis by macrophages.
      Thus, FXIII may function in innate immunity. Congenital FXIII deficiency due to
      defective F13-A genes manifests as a life-long bleeding tendency, abnormal wound
      healing, and recurrent miscarriage. Although congenital FXIII-B deficiency used
      to be thought rare, reports of such cases have increased recently. As the
      bleeding tendency is often mild, patients with FXIII-B deficiency may be
      overlooked by physicians. Patients with acquired FXIII deficiency, in particular
      those with autoimmune hemorrhaphilia due to anti-FXIII antibodies, are on the
      increase, at least in Japan. It is important to diagnose such cases as early as
      possible, and to treat them with immunosuppression in combination with FXIII
      replacement therapy as their bleeding symptoms can be life-threatening.

PMID- 22477543
TI  - Telmisartan 80 mg/hydrochlorothiazide 25 mg provides clinically relevant blood
      pressure reductions across baseline blood pressures.
AB  - INTRODUCTION: Most patients with hypertension require combination therapy to
      achieve optimal reduction of blood pressure (BP). The angiotensin II receptor
      blocker, telmisartan, provides 24-hour BP-lowering efficacy and is proven to
      prevent cardiovascular morbidity in high-risk patients. METHODS: Pooled data from
      seven randomized controlled trials (3,654 patients with stage 1-2 hypertension)
      were analyzed to investigate the BP-lowering efficacy of telmisartan 40 or 80 mg
      (T40 or T80) in combination with hydrochlorothiazide 12.5 or 25 mg (H12.5 or H25)
      when compared with either placebo or telmisartan monotherapy, relative to
      patients' baseline BP. BP-lowering efficacy was also assessed in subpopulations.
      The primary endpoint was the change from baseline in seated trough clinic
      systolic BP (SBP) and diastolic BP (DBP). RESULTS: In the overall population and
      across all baseline BP categories, T40/H12.5, T80/H12.5, and T80/H25 resulted in
      additional BP reductions to those provided by telmisartan monotherapy. In
      patients with baseline SBP>=170 mmHg, T80/H25 effected a mean SBP change of -39.2
      mmHg compared with changes of -25.5 mmHg and -8.3 mmHg observed with T80 and
      placebo treatment, respectively. Mean DBP changes were -20.4 mmHg T80/H25, -12.2
      T80 and -5.9 placebo in patients with baseline DBP>=105 mmHg. T80/H25 also
      resulted in larger BP reductions than telmisartan monotherapy in black patients
      with hypertension, irrespective of baseline BP. In patients with hypertension
      with type 2 diabetes and in patients with moderate or severe renal impairment,
      both T80/H12.5 and T80/H25 were more effective than monotherapy in reducing BP in
      all baseline BP categories. CONCLUSION: Combination treatment of telmisartan and
      hydrochlorothiazide results in large and clinically relevant BP reductions
      additional to those provided by monotherapy.

PMID- 22477544
TI  - Effect of myrtol standardized and other substances on the respiratory tract:
      ciliary beat frequency and mucociliary clearance as parameters.
AB  - INTRODUCTION: Myrtol standardized is a phytomedicine obtained by distillation,
      consisting of many constituents. In vitro and in vivo, the major monterpenes, d
      limonene, 1,8-cineole, and alpha-pinene, are used as biological marker
      substances. Myrtol standardized has secretolytic, secretomotor, and mucolytic
      effects in addition to anti-inflammatory and antioxidative actions. The aim of
      the study was to investigate the effects of different concentrations of Myrtol
      standardized on in vivo mucociliary clearance in mice and the ciliary beat
      frequency (CBF) in rat tracheal rings. METHODS: Data regarding the effects of 1,8
      cineole and N-acetylcysteine (NAC) were compared. Salbutamol was used as a
      positive control. CBF was measured using rat tracheal explants and a high-speed
      video camera linked to a microscope with specific software equipment. Mucociliary
      clearance was determined using the microdialysis technique, which measured the
      acceleration of a fluorescent sample in the trachea in vivo. RESULTS: Myrtol
      standardized accelerated both CBF and mucociliary transport in a concentration
      dependent manner. Significant effects were seen at a concentration of 0.01%
      Myrtol regarding CBF (P<0.01) and 17.1 mg/kg body weight regarding mucociliary
      clearance experiments (P<0.05) according to doses relevant to humans. The 1,8
      cineole dosage relative to humans only accelerated the mucociliary clearance in
      vivo without having an effect on the CBF. Extremely high doses of Myrtol were not
      able to additionally increase the CBF effect in comparison to salbutamol.
      Compared to NAC, also used in a dosage relative to humans, Myrtol standardized
      showed a tendency to be more effective. CONCLUSION: In summary, the present data
      suggest that Myrtol standardized is a pharmacologically important drug which,
      when used at a dose relative to humans, shows positive effects on both measured
      parameters, CBF and mucociliary clearance, in vivo.

PMID- 22477545
TI  - Potential role of high molecular weight calmodulin-binding protein in cardiac
      injury.
AB  - Ca(2+) is a major determinant of many biochemical processes in various cell types
      and is a critical second messenger in cell signalling. High molecular weight
      calmodulin-binding protein (HMWCaMBP) was originally discovered and purified in
      the authors' laboratory. It was identified as a homologue of calpastatin - an
      inhibitor of Ca(2+)-activated cysteine proteases (calpains). Decreased expression
      of HMWCaMBP in ischemia suggests that it is proteolyzed by calpains during
      ischemia and reperfusion. In normal myocardial muscle, HMWCaMBP may protect its
      substrate from calpains, but during an early stage of ischemia/reperfusion with
      increased Ca(2+) influx, calpain activity exceeds HMWCaMBP activity, leading to
      proteolysis of HMWCaMBP and other protein substrates, resulting in cellular
      damage. The role of HMWCaMBP in ischemia/reperfusion is yet to be explored. The
      present review summarizes developments from the authors' laboratory in the area
      of HMWCaMBP.

PMID- 22477546
TI  - Cardiac device-related endocarditis: Epidemiology, pathogenesis, diagnosis and
      treatment - a review.
AB  - Cardiac device-related endocarditis (CDE) is a phenomenon for which incidence is
      on the rise; it presents difficult management problems to the clinician. On one
      hand, there is the patient who needs the implanted device, and the potential
      morbidity and mortality associated with its removal. On the other hand, there is
      the problem of a persistent infection - usually acquired during insertion of an
      electrical device - that is resistant to many antibiotics, has a high recurrence
      rate, and necessitates an extensive operation to remove the device if removal is
      delayed. Most studies recommend device and metal lead replacement if CDE occurs.
      The aim of the present review is to raise awareness of CDE among clinicians, and
      to provide an appropriate approach to its management.

PMID- 22477541
TI  - Protein C anticoagulant and cytoprotective pathways.
AB  - Plasma protein C is a serine protease zymogen that is transformed into the
      active, trypsin-like protease, activated protein C (APC), which can exert
      multiple activities. For its anticoagulant action, APC causes inactivation of the
      procoagulant cofactors, factors Va and VIIIa, by limited proteolysis, and APC's
      anticoagulant activity is promoted by protein S, various lipids, high-density
      lipoprotein, and factor V. Hereditary heterozygous deficiency of protein C or
      protein S is linked to moderately increased risk for venous thrombosis, while a
      severe or total deficiency of either protein is linked to neonatal purpura
      fulminans. In recent years, the beneficial direct effects of APC on cells which
      are mediated by several specific receptors have become the focus of much
      attention. APC-induced signaling can promote multiple cytoprotective actions
      which can minimize injuries in various preclinical animal injury models.
      Remarkably, pharmacologic therapy using APC demonstrates substantial
      neuroprotective effects in various murine injury models, including ischemic
      stroke. This review summarizes the molecules that are central to the protein C
      pathways, the relationship of pathway deficiencies to venous thrombosis risk, and
      mechanisms for the beneficial effects of APC.

PMID- 22477547
TI  - Fate of the external carotid artery following carotid interventions.
AB  - OBJECTIVE: The external carotid artery (ECA) is an important collateral pathway
      for cerebral blood flow. Carotid artery stenting (CAS) typically crosses the ECA,
      while carotid endarterectomy (CEA) includes deliberate ECA plaque removal. The
      purpose of the present study was to compare the long-term patency of the ECA
      following CAS and CEA as determined by carotid duplex ultrasound. METHODS: Duplex
      ultrasounds and hospital records were reviewed for consecutive patients
      undergoing CAS between February 2002 and April 2008, and were compared with those
      undergoing CEA in the same time period. Preoperative and postoperative ECA peak
      systolic velocities were normalized to the common carotid artery (CCA) as ECA/CCA
      ratios. A significant (80% or greater) ECA stenosis was defined as an ECA/CCA
      ratio of 4.0. A change of ratio by more than 1 was defined as significant. Data
      were analyzed using Student's t test and chi(2) analysis. RESULTS: A total of 86
      CAS procedures in 83 patients were performed (81 men, mean age 69.9 years). Among
      them, 38.4% of patients had previous CEA, 9.6% of whom had contralateral internal
      carotid artery occlusion. Sixty-seven CAS and 65 CEA patients with complete
      duplex data in the same time period were included in the analyses. There was no
      difference in the incidence of severe ECA stenosis on preoperative ultrasound
      evaluations. During a mean follow-up of 34 months (range four to 78 months),
      three postprocedure ECA occlusions were found in the CAS group. The likelihood of
      severe stenosis or occlusion following CAS was 28.3%, compared with 11% following
      CEA (P<0.025). However, 62% of CEA patients and 57% of CAS patients had no
      significant change in ECA status. Reduction in the patient's degree of ECA
      stenosis was observed in 9.4% of CAS versus 26.6% of CEA patients. Overall,
      immediate postoperative ratios of both groups were slightly improved, but there
      was a trend of more disease progression in the CAS group during follow-up.
      CONCLUSION: CAS is associated with a higher incidence of post-procedure ECA
      stenosis. Despite the absence of neurological symptoms, a trend toward late
      disease progression of ECA following CAS warrants long-term evaluation.

PMID- 22477548
TI  - QT interval dispersion pattern in patients with acute ischemic stroke: Does the
      site of infarction matter?
AB  - BACKGROUND: QT interval dispersion (QTD) is an independent predictor of outcome
      following acute neurological events. OBJECTIVES: To explore QTD patterns and
      their relation to the affected cerebral region in patients with acute ischemic
      stroke. METHODS: Thirty patients with first acute ischemic stroke (the first
      stroke the patients had ever experienced) (study group) and 30 healthy controls
      (control group) were enrolled. Patients underwent magnetic resonance imaging to
      confirm and localize cerebral damage. Patients in the study group were further
      subdivided according to the site of infarction into four subgroups - namely,
      cortical, subcortical, brain stem and cerebellar infarctions, as well as
      according to insular involvement. All included subjects underwent 12-lead
      electrocardiography to measure QTD and corrected QT dispersion (QTcD). RESULTS:
      In the study group, both QTD and QTcD on the first hospitalization day were
      significantly higher than in the control group (P<0.05 for both). Similarly, in
      the study group, both QTD and QTcD values on the first hospitalization day were
      significantly higher than the respective values on the third day (P<0.001 for
      both). No significant differences were found among the four territorial
      subgroups, or between right- and left-sided subgroups, regarding QT interval
      measurements, whether on the first or third day (P>0.05 for all). However, 'first
      day' QTD and QTcD of patients with insular involvement were significantly higher
      than in those without such involvement (P<0.001 for both). CONCLUSIONS: Both QTD
      and QTcD increased significantly in patients with acute ischemic stroke during
      the first hospitalization day. This increase of 'first-day' QTD and QTcD was
      significantly higher in patients with insular involvement than in those without
      such involvement.

PMID- 22477549
TI  - A retrospective analysis of the incidence of hemolysis in type and screen
      specimens from trauma patients.
AB  - BACKGROUND: Hemolysis of blood samples has been a concern in hospitals.
      Currently, residents and nurses have replaced traditional teams of skilled
      phlebotomists for both routine and 'stat' blood draws. Although this leads to a
      decreased operating cost for institutions, the lack of skill and experience leads
      to a higher percentage of hemolyzed specimens. OBJECTIVE: To determine the
      incidence of hemolyzed 'type and screen' blood samples at Staten Island
      University Hospital (SIUH) (New York, USA). METHODS: The study group comprised
      615 consecutive trauma patients at SIUH between July 2006 and June 2007. Patients
      were treated according to the Advanced Trauma Life Support protocol. The primary
      survey for a trauma patient consists of 'airway', 'breathing' and 'circulation'.
      The primary objective of 'circulation' is to establish vascular access and
      collect blood samples for analysis. The SIUH in-house laboratory provided all of
      the reports. RESULTS: Of the 615 samples collected, 155 samples (25.2%) were
      hemolyzed. CONCLUSIONS: The hemolysis rate of 25.2% for type and screen samples
      is higher than previously reported in the literature. The data suggest that the
      high rate of hemolysis in these trauma patients is due to the residents' lack of
      experience and skills required to obtain an adequate blood draw.

PMID- 22477550
TI  - Effect of enoxaparin on peak and trough levels of antifactor Xa in patients with
      a creatinine clearance of less than 30 mL/min.
AB  - AIM: To assess whether there was an increased risk of bleeding with enoxaparin in
      patients with a creatinine clearance (CCT) of less than 30 mL/min. METHODS:
      Patients with a CCT of less than 30 mL/min who were given enoxaparin 1 mg/kg/day
      were included. Antifactor Xa levels (peak and trough) were measured after three
      doses (days) of enoxaparin. The peak antifactor Xa levels were measured 4 h after
      the third enoxaparin dose, and the trough levels of antifactor Xa were measured
      12 h and 24 h after the third enoxaparin dose. Basic demographic data such as
      age, sex, race, diagnosis and creatinine values were assessed at baseline.
      Adverse events were monitored and recorded. Domain-specific review board approval
      was obtained before the present study began. RESULTS: A total of 15 patients were
      recruited for the present study. Three patients dropped out of the study;
      therefore, 12 patients were analyzed. The mean age of the 12 patients was 69.25
      years (range 41 to 89 years). There were six men and an equal number of women.
      There were eight Chinese patients, three Malay patients and one Indian patient.
      The indication for anticoagulation was deep vein thrombosis in seven patients,
      non-ST elevation myocardial infarction in four patients and atrial fibrillation
      in one patient. There were no adverse events noted in any patient. CONCLUSION: It
      is safe to administer enoxaparin once a day to patients with renal impairment and
      a CCT of less than 30 mL/min.

PMID- 22477551
TI  - Low levels of soluble receptor for advanced glycation end products in non-ST
      elevation myocardial infarction patients.
AB  - BACKGROUND: Interaction of the receptors for advanced glycation end products
      (RAGEs) with advanced glycation end products (AGEs) results in expression of
      inflammatory mediators (tumor necrosis factor-alpha [TNF-alpha] and soluble
      vascular cell adhesion molecule-1 [sVCAM-1]), activation of nuclear factor-kappa
      B and induction of oxidative stress - all of which have been implicated in
      atherosclerosis. Soluble RAGE (sRAGE) acts as a decoy for the RAGE ligand and is
      protective against atherosclerosis. OBJECTIVES: To determine whether levels of
      serum sRAGE are lower, and whether levels of serum AGEs, TNF-alpha and sVCAM-1
      are higher in non-ST elevation myocardial infarction (NSTEMI) patients than in
      healthy control subjects; and whether sRAGE or the ratio of AGEs to sRAGE
      (AGEs/sRAGE) is a predictor/biomarker of NSTEMI. METHODS: Serum levels of sRAGE,
      AGEs, TNF-alpha and sVCAM-1 were measured in 46 men with NSTEMI and 28 age- and
      sex-matched control subjects. Angiography was performed in the NSTEMI patients.
      RESULTS: sRAGE levels were lower, and levels of AGEs, TNF-alpha, sVCAM-1 and
      AGEs/sRAGE were higher in NSTEMI patients than in control subjects. sRAGE levels
      were negatively correlated with the number of diseased coronary vessels, serum
      AGEs, AGEs/sRAGE, TNF-alpha and sVCAM-1. The sensitivity of the AGEs/sRAGE test
      is greater than that of the sRAGE test, while the specificity and predictive
      values of the sRAGE test are greater than those of the AGEs/sRAGE test for
      identifying NSTEMI patients. CONCLUSIONS: Serum levels of sRAGE were low in
      NSTEMI patients, and were negatively correlated with extent of lesion,
      inflammatory mediators, AGEs and AGEs/sRAGE. Both sRAGE and AGEs/sRAGE may serve
      as biomarkers/predictors for identifying NSTEMI patients.

PMID- 22477552
TI  - Prevention of contrast-induced nephropathy: A randomized controlled trial of
      sodium bicarbonate and N-acetylcysteine.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) continues to be a common cause of
      acute renal failure in high-risk patients undergoing radiocontrast studies.
      However, there is still a lack of consensus regarding the most effective measures
      to prevent CIN. METHODS: ONE HUNDRED EIGHTEEN PATIENTS WITH DIABETES MELLITUS
      AND/OR RENAL INSUFFICIENCY, SCHEDULED FOR CORONARY ANGIOGRAPHY OR INTERVENTION,
      WERE RANDOMLY ASSIGNED TO ONE OF FOUR TREATMENT GROUPS: intravenous (IV) 0.9%
      NaCl alone, IV 0.9% NaCl plus N-acetylcysteine (NAC), IV 0.9% sodium bicarbonate
      (NaHCO(3)) alone or IV 0.9% NaHCO(3) plus NAC. All patients received IV hydration
      as a preprocedure bolus and as maintenance. Iso-osmolar contrast was used in all
      patients. CIN was defined as an increase of greater than 25% in the serum
      creatinine concentration from baseline to 72 h. RESULTS: The overall incidence of
      CIN was 6%. There was no statistically significant difference in the incidence of
      CIN among the groups. There was a CIN incidence of 7% in the NaCl only group, 5%
      in the NaCl/NAC group, 11% in the NaHCO(3) only group and 4% in the NaHCO(3)/NAC
      group (P=0.86). The maximum increase in serum creatinine was 14.14+/-12.38
      MUmol/L in the NaHCO(3) group, 10.60+/-29.14 MUmol/L in the NaCl only group,
      9.72+/-13.26 MUmol/L in the NaCl/NAC group and 0.177+/-15.91 MUmol/L for the
      NaHCO(3)/NAC group (P=0.0792). CONCLUSION: CIN in high-risk patients may be
      effectively minimized solely through the use of an aggressive hydration protocol
      and an iso-osmolar contrast agent. The addition of NaHCO(3) and/or NAC did not
      have an effect on the incidence of CIN.

PMID- 22477553
TI  - Endometriosis causing lower extremity deep vein thrombosis - case report and
      review of the literature.
AB  - Endometriosis is a medical condition in women wherein endometrial cells deposited
      in the area outside the uterine cavity are influenced by hormonal changes, and
      produce symptoms depending on the site of implantation. A unique case of
      retroperitoneal endometriosis causing deep vein thrombosis from extrinsic
      compression of the right iliac vein is described. Clinical presentation with
      cyclical leg swelling, coincidental with menstruation and culminating with deep
      vein thrombosis, although very suggestive, has not been previously reported.

PMID- 22477554
TI  - Symptomatic inferior vena cava perforation by a retrievable filter: Report of two
      cases and a literature review.
AB  - Inferior vena cava filters have been used frequently for decades to prevent
      pulmonary embolism in medical, surgical and trauma patients. With the advent of
      temporary or retrievable filters, the use of these filters has increased
      substantially. However, the enhanced design and attributes that make these
      devices attractive for short-term benefit and retrieval are not without risk. Two
      cases of symptomatic inferior vena cava wall penetration are reported - one of
      which required surgical intervention.

PMID- 22477555
TI  - Hibernating kidney - a case report.
AB  - A 75-year-old woman presented with a two-month history of progressive dyspnea on
      exertion. On physical examination, her blood pressure was 148/90 mmHg, jugular
      venous pressure was 10 cmH(2)O with a prominent V wave, right ventricular heave
      was present and she had a systolic murmur at the right upper sternal border that
      varied with inspiration. The patient had a pulsatile liver, mild ascites and
      systolic bruits over both kidneys, with the diastolic component on the left side.

PMID- 22477556
TI  - Use of an autologous artery for tibial artery bypass in a trauma patient.
AB  - Peripheral artery bypass grafting is a commonly performed procedure. The present
      report describes the use of an autologous artery for tibial artery bypass graft
      following a gunshot wound to the calf. Approximately 4 cm of proximal peroneal
      artery was harvested for use as a bypass graft. At one year postoperatively, an
      arterial duplex scan showed patency of the tibioperoneal trunk to the posterior
      artery bypass.

PMID- 22477558
TI  - A fable.

PMID- 22477557
TI  - Introducing the at-risk average causal effect with application to HealthWise
      South Africa.
AB  - Researchers often hypothesize that a causal variable, whether randomly assigned
      or not, has an effect on an outcome behavior and that this effect may vary across
      levels of initial risk of engaging in the outcome behavior. In this paper, we
      propose a method for quantifying initial risk status. We then illustrate the use
      of this risk-status variable as a moderator of the causal effect of leisure
      boredom, a non-randomized continuous variable, on cigarette smoking initiation.
      The data come from the HealthWise South Africa study. We define the causal
      effects using marginal structural models and estimate the causal effects using
      inverse propensity weights. Indeed, we found leisure boredom had a differential
      causal effect on smoking initiation across different risk statuses. The proposed
      method may be useful for prevention scientists evaluating causal effects that may
      vary across levels of initial risk.

PMID- 22477559
TI  - Establishing operations and the mand.
AB  - In Verbal Behavior Skinner identifies a small number of elementary verbal
      relations, one of which is the mand. Because its introduction is at first in
      terms of unlearned motivative variables, and because the mand's relation to prior
      controlling events is quite complex, its general significance has probably been
      underestimated. An extensive treatment of establishing operations, including the
      warning and the blocked-response conditioned establishing operations is provided,
      followed by a description of the mand in terms of such operations. The importance
      of the mand for language training programs is suggested, as well as the reasons
      why it is typically neglected in such programs.

PMID- 22477560
TI  - Event-governed and verbally-governed behavior.
AB  - A NUMBER OF STATEMENTS PRESCRIBE BEHAVIOR: apothegms, maxims, proverbs,
      instructions, and so on. These differing guides to conduct present varieties of
      the dictionary definition of "rules." The term "rules" thus defines a category of
      language usage. Such a term, and its derivative, "rule-governed," does not
      address a controlling relation in the analysis of verbal behavior. The prevailing
      confounding of a category of language with a category of verbal behavior appears
      related to a lack of understanding as to what distinguishes verbal behavior from
      other behavior. Verbal behavior is a behavior-behavior relation in which events
      are contacted through the mediation of another organism's behavior specifically
      shaped for such mediation by a verbal community. It contrasts with behavior that
      contacts events directly, and shaped directly by the features of those events.
      Thus we may distinguish between two large classes of behavior by whether it is
      behavior controlled by events, or behavior controlled verbally. However, the
      functional controls operative with both classes of behavior do not differ.

PMID- 22477561
TI  - Promoting the behaviorological analysis of verbal behavior.
AB  - An important contribution of radical behavioral science is its analysis of verbal
      behavior. Slowly but surely an increasing number of efforts verify the
      propositions explicit or inherent in Skinner's theory of verbal behavior, or
      apply his analysis to clinical or educational practice. But both the theory and
      the effort to apply it are met with silence. Such silent neglect simply varies
      the calumnious attention usually given to behavioristic science. In recent years
      several papers have called attention to how non-behaviorists have habitually
      misrepresented the science of behavior and its underlying philosophy of radical
      behaviorism (Cooke, 1984; DellaLana, 1982; Morris, 1985; Todd, 1987a; Todd &
      Morris, 1981; Todd & Morris, 1983). These authors offer various solutions. Their
      preferred strategy stresses an increased effort to disseminate accurate
      information about behavioristic science to the press and to the world at large.
      They generally address, however, errors of commission, not omission. Further,
      their solutions tend to dwell on "processes" instead of "products." This paper
      first reviews the problem of misrepresentation of the science. It then addresses
      the principal error of omission in the psychological literature, and offers a
      solution based on achieving new products resulting from new verbal behavior
      technology.

PMID- 22477562
TI  - Fixed-interval and fixed-ratio reinforcement schedules with human subjects.
AB  - Operant laboratory studies were conducted as part of the regular activities of a
      psychiatric research ward. This report includes only some early data obtained
      from the ward staff, not the patients. A multiple schedule having alternating
      fixed-ratio and fixed-interval components permitted observations of acquisition
      and maintenance of behavior at low schedule values, transition to and final
      performance at greater schedule values, and behavioral changes after a limited
      hold contingency was added to the fixed-interval. Prior to the added limited
      hold, subjects used watches to time the interval, and usually responded only once
      before obtaining each fixed-interval reinforcement. Short limited-hold values
      eliminated clock watching and increased fixed-interval responding. Subjects
      communicated freely with each other, and it was clear that their performances
      were controlled both by the contingencies and by instructions. Just as clearly,
      the instructions themselves were controlled by the contingencies. It was
      concluded that the kinds of verbal control that were responsible for
      "nonstandard" fixed-interval performances did not require the postulation of any
      new behavioral principles.

PMID- 22477563
TI  - Establishing a generalized autoclitic repertoire in preschool children.
AB  - Skinner's (1957) analysis of language presents the notion of secondary verbal
      behavior, some of which is termed "autoclitic." These kinds of verbal responses
      are dependent upon primary verbal behavior and are controlled by some feature of
      the primary verbal relationship (e.g., mand, tact, etc.). In this study preschool
      children were trained to make autoclitic responses evoked by the weakness of the
      relation controlling a primary tact response. A method for training tacting of
      private events known as "public accompaniment" was utilized. Theoretical issues
      related to the nature of autoclitic behavior as well as practical concerns for
      training are discussed.

PMID- 22477564
TI  - A preliminary investigation of the consequences that define the mand and the
      tact.
AB  - Skinner (1957) proposed that the mand and the tact differed with respect to their
      unique antecedents and consequences. The present study examined the specific
      reinforcement characteristic of the mand, and the nonspecific reinforcement
      characteristic of the tact. A severely mentally impaired individual who used sign
      language served as subject. A concurrent-chain with latency measures and choice
      was used. The results showed that specific reinforcement produced stronger verbal
      behavior than nonspecific reinforcement, but only when response strength was
      measured in terms of latency and choice. These data lend support to Skinner's
      assertion that the mand and the tact are different operants. These results also
      have practical significance in that they may lead to more effective work with
      individuals who have speech and language impairments.

PMID- 22477565
TI  - [The German severe asthma registry].

PMID- 22477566
TI  - [Farmer's lung antigens in Germany].
AB  - Recent studies suggest that besides the long-known farmer's lung antigen sources
      Saccharopolyspora rectivirgula (Micropolyspora faeni), Thermoactinomyces
      vulgaris, and Aspergillus fumigatus, additionally the mold Absidia (Lichtheimia)
      corymbifera as well as the bacteria Erwinia herbicola (Pantoea agglomerans) and
      Streptomyces albus may cause farmer's lung in Germany. In this study the sera of
      64 farmers with a suspicion of farmer's lung were examined for the following
      further antigens: Wallemia sebi, Cladosporium herbarum, Aspergillus versicolor,
      and Eurotium amstelodami. Our results indicate that these molds are not frequent
      causes of farmer's lung in Germany.

PMID- 22477567
TI  - [Lung function diagnostics for the small airways].
AB  - In the recent years growing interest has focused on the involvement of the distal
      airways (internal diameter < 2 mm) in obstructive lung diseases and other
      pulmonary conditions. Inflammation in the small airways seems to play a major
      role in severe and uncontrolled asthma as a major determinant of airflow
      obstruction. Thus, small airways represent an important target for inhalation
      therapy. Currently there is no accepted single lung function parameter to detect
      small airway dysfunction. Various invasive and non-invasive techniques have been
      described. In future, non-invasive lung function testing will gain more
      importance. Using spirometry or body plethysmography, lung function parameters
      such as the ratio of forced vital capacity to slow vital capacity (FVC/SVC) and
      the residual volume (RV) can provide information about air trapping in small
      airway disease. Recent data show that techniques such as impulse oscillometry,
      nitrogen washout testing and analysis of exhaled nitric oxide are promising tools
      to assess involvement of the small airways. Impulse oscillometry is a sensitive
      method to calculate peripheral airway resistance, nitrogen washout allows one to
      detect air trapping and inhomogeneous ventilation in the distal lung, and the
      alveolar nitric oxide concentration represents a marker of peripheral
      inflammation. Further studies are needed to validate these functional tests or
      their combination for diagnosis and assessment of treatment response in pulmonary
      diseases involving small airways.

PMID- 22477568
TI  - [Asbestos-induced laryngeal carcinoma in situ].

PMID- 22477569
TI  - [Is the telemedical management of COPD patients of any value?].

PMID- 22477570
TI  - Evidence-based management of carotid artery disease.
AB  - Stroke is a major cause of disability and mortality, and a major cause of stroke
      is carotid artery stenosis. This stenosis is caused by carotid atherosclerotic
      plaques, the prevention and management of which are the key to avoiding many
      resultant strokes. The plaque can either embolize to a cerebral artery or build
      up in a carotid artery, ultimately resulting in thrombosis and total occlusion.
      Noninvasive testing can now make the diagnosis of carotid stenosis. Medical
      management with plaque stabilization and platelet inhibition plays a key role in
      stroke prevention. Carotid endarterectomy and invasive carotid angioplasty
      stenting are also important for lesions with extensive progression, and patients
      with a very high overall risk may especially benefit from the latter procedure. A
      medical-surgical team approach is now greatly contributing to the avoidance of
      stroke and its devastation.

PMID- 22477571
TI  - Cost-benefit comparison of hemodialysis access creation in a developing country
      and North American centres.
AB  - OBJECTIVE: It has been suggested that vascular access operations should only be
      performed in high-volume centres to ensure good outcomes. Vascular access
      operations have been routinely performed in the Cayman Islands since 2005.
      However, with an estimated population of 45,000 persons, only a small number of
      patients require vascular access in any given interval. A cost-benefit analysis
      of this practice was performed. METHODS: All patients who had vascular access
      operations over four years were retrospectively identified. Two groups were
      defined - the local group, who had operations performed by surgeons in the Cayman
      Islands, and the offshore group, who were transferred off the island and had
      operations overseas. Cumulative cost, morbidity, patency and failure rates were
      compared. Significance was considered present with a two-tailed P<=0.05. RESULTS:
      There were 14 patients in the local group and 22 in the offshore group. The mean
      cost of access creation was 6.9 times greater in the offshore group (US$26,883.36
      versus US$3,913.33; P<0.001). The likelihood of the use of arteriovenous grafts
      was significantly greater in the offshore group (P=0.04). When therapeutic
      outcomes were compared, there were no differences in primary or secondary
      failure, primary or secondary patency, or overall access-specific morbidity.
      CONCLUSIONS: In the present setting, vascular access creation exceeded all the
      goals set by the National Kidney Foundation Kidney Disease Outcomes Quality
      Initiative and the Fistula First Breakthrough Initiative. Compared with overseas
      centres, this is being achieved at a significantly lower cost, with a greater
      likelihood of native fistula use and similar therapeutic outcomes.

PMID- 22477572
TI  - Augmentation of venous, arterial and microvascular blood supply in the leg by
      isometric neuromuscular stimulation via the peroneal nerve.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is the formation of a blood clot within
      the deep veins. During periods of sitting, blood flow is decreased and this
      contributes to an increased risk of DVT. Trials have shown that 5% to 10% of
      passengers undertaking long-haul flights develop asymptomatic calf DVT. AIM: To
      investigate the safety and efficacy of a novel neuromuscular device that augments
      peripheral blood flow. METHODS: Thirty healthy volunteers were assessed while
      seated. Each subject had one leg connected to the stimulator and the other leg
      immobile acting as control. Fifteen sequential electrical stimulations were
      applied for 5 min each followed by a 10 min recovery phase. The following
      noninvasive measurements were performed before, during and after the stimulation
      programs: photoplethysmography, strain gauge plethysmography, laser Doppler
      fluxmetry, transcutaneous oxygen tension, pulse oximetry, superficial femoral
      vein blood flow and vessel diameter (ultrasound); discomfort questionnaires were
      also administered. RESULTS: During neuromuscular stimulation, significant
      increases in blood volume flow and velocity and skin capillary blood flow were
      found; transdermal skin oxygen levels were maintained. No changes were observed
      in heart rate, blood pressure, oxygen saturation or femoral vein vessel diameter.
      CONCLUSIONS: Using a newly developed device, electrical nerve stimulation of the
      lower leg significantly increased blood flow; the device in the present study is,
      therefore, a promising tool for the development of a novel DVT prevention device.
      Because this method of electrical nerve stimulation is virtually pain free, the
      present study has significant implications for the prevention of DVT in
      hospitals, outpatient settings and community care settings, as well as in
      preventing travel-related thrombosis.

PMID- 22477573
TI  - Edaravone protects against tissue damage in the lung and kidney induced by
      myonephropathic metabolic syndrome.
AB  - PURPOSE: Free radicals have been implicated in myonephropathic metabolic syndrome
      (MNMS), which not only damages muscles but also the kidneys and lungs. It was
      recently shown that the free radical scavenger edaravone suppressed reperfusion
      injury in rat extremities. The present study evaluated whether edaravone also
      protects against MNMS-induced tissue damage in the lungs and kidneys after
      reperfusion injury of rat extremities. METHODS: Ten male Lewis rats (mean [+/-
      SD] weight 508+/-33 g) were divided into two groups. The MNMS models were created
      by clamping the bilateral common femoral arteries for 5 h, followed by
      declamping. In another group, 3.0 mg/kg of edaravone was injected into the
      peritoneal cavity before clamping the bilateral common femoral arteries. Five
      hours after starting reperfusion, the kidneys and lungs were harvested from each
      rat for histological study (n=10). Kidney damage was expressed as the number of
      infiltrating cells in the glomeruli. Lung damage was expressed as the percentage
      area of the alveolar wall thickness with cellular infiltration, using
      computerized densitometry. RESULTS: Kidneys in the edaravone group showed less
      cellular infiltration than in the control group (62.2+/-2.4 cells versus 75.8+/
      3.6 cells per glomerulus, respectively; P=0.002). Lungs in the edaravone group
      also showed a significantly lower percentage of damaged lung tissue area than in
      the control group (20.5+/-1.5% versus 63.6+/-2.8%, respectively; P<0.001).
      CONCLUSION: The results suggest that the free radical scavenger edaravone might
      protect against kidney and lung damage induced by MNMS after reperfusion injury
      of rat extremities.

PMID- 22477574
TI  - Claudication pain in the left arm of a coronary artery bypass graft patient using
      crutches: Coronary subclavian steal syndrome - a case report.
AB  - A 77-year-old male former smoker with hypercholesterolemia and diabetes, who
      underwent coronary artery bypass graft surgery three years before admission and
      right carotid endarterectomy four years before admission, presented with recent
      onset exertional chest pain. His medical history revealed that the chest pain was
      preceded by gradually worsening exertional claudication pain in his left arm when
      he was using crutches. The chest pain was similar to the pain he experienced
      before the coronary artery bypass graft surgery was performed. Coronary
      angiography and bypass graft imaging showed significant stenosis of the left
      subclavian artery proximal to the origin of the left internal mammary artery
      bypass, decreased flow in the left internal mammary artery with partial
      retrograde filling from the left anterior descending artery, and severe narrowing
      of the left vertebral artery with preserved centrifugal flow. Percutaneous stent
      implantation into the left subclavian artery was performed together with proximal
      balloon angioplasty of the left vertebral artery. The patient has been symptom
      free since the stent implantation.

PMID- 22477575
TI  - Persistent bilateral sciatic artery: Report of a rare case.
AB  - The sciatic artery - a rare finding on autopsy - and continuation of the inferior
      gluteal artery has been reported previously. On a routine dissection, bilateral
      persistent sciatic arteries were found in both thighs of a female cadaver. This
      provided evidence that the sciatic artery follows the sciatic nerve, supplies the
      back of the thigh and finally joins the popliteal artery near the knee. The
      profunda femoris artery was completely absent bilaterally. The present report
      strengthens the view that the sciatic artery plays a major role in supplying
      blood to the lower limbs in utero and its existence after birth may have
      significant clinical importance.

PMID- 22477576
TI  - Unusual presentation of Monckeberg's sclerosis in the thyroid vessels of three
      female patients.
AB  - Histopathological findings of Monckeberg's sclerosis in the thyroid vessels of
      three female patients are described. Two of the patients presented with papillary
      carcinoma and the third presented with two cystic adenomatous nodules. Lesions of
      chronic lymphocytic thyroiditis were observed in two of the cases. The presence
      of Monckeberg's sclerosis is an indication for further examination of patients'
      vascular systems because of the high risk for cardiovascular events.

PMID- 22477577
TI  - Large pulmonary artery aneurysm associated with Marfan syndrome.
AB  - Pulmonary artery aneurysms are rare, and published data on the subject are
      limited. The first case of Marfan syndrome associated with a large pulmonary
      artery aneurysm complicated by pulmonary artery thrombi and pulmonary
      hypertension is described. Serial echocardiograms showed progressive dilation of
      the aneurysm, which reached a massive size of 90 mm. Cardiac catheterization,
      pulmonary angiography and computed tomography angiography were used in the
      preoperative evaluation. The patient died suddenly while awaiting a decision for
      surgical intervention, thereby underscoring the need for aggressive management.

PMID- 22477578
TI  - Adverse effect of low-dose amiodarone mimicking pulmonary malignancy.
AB  - A 74-year-old woman presented with a one-week history of persistent cough. A
      chest x-ray and computed tomography images revealed features mimicking lung
      cancer, which included a large solitary consolidation and hilar lymphadenopathy.
      She had received low-dose amiodarone (200 mg/day) for treatment of atrial
      fibrillation for more than 2.5 years. The tumour-like abnormalities did not
      disappear until the discontinuation of amiodarone therapy. The finding of low
      dose amiodarone causing tumour-like abnormalities on a chest x-ray is unique.
      Once amiodarone-induced tumour-like changes are diagnosed, therapeutic options
      are limited. In most cases, the tumour-like changes are reversible, if diagnosed
      early. An unusual case involving amiodarone-induced pulmonary abnormalities is
      reported, followed by a review of the relevant literature.

PMID- 22477581
TI  - A functional analysis of a behavior analyst's functional analysis.

PMID- 22477580
TI  - A functional analysis of mentalistic terms in human observers.
AB  - This paper, and the following paper by M.J. Dougher (1989), were originally given
      as part of a symposium presented at the 1984 meeting of the Association for
      Behavior Analysis (R. Schnaitter, Chair). The symposium included two other papers
      on the same theme by Diane Spooner and Diane Mercier, and the discussant was
      Willard Day. The concept of the symposium was to use the following paper
      (Leigland) as a basis for a demonstration of what has been termed the "Reno
      methodology," a method for the interpretation of verbal behavior developed by
      Willard Day and his students at the University of Nevada, Reno. Essentially, the
      project may be described in the following way: the controlled environment
      behavior interactions of a pigeon in an operant chamber gave rise to explanatory
      verbal behavior on the part of observing human subjects, and the controlling
      relations with respect to the latter gave rise to the verbal behavior contained
      in Leigland's report. The controlling relations to be discriminated with respect
      to Leigland's verbal behavior were then the subject of Dougher's analysis in the
      report that follows. Dougher's report, then, uses Leigland's report as a source
      of verbal behavior to be interpreted, using the practices developed by the Reno
      group as a method.

PMID- 22477579
TI  - Antihypertensive effects of dietary protein and its mechanism.
AB  - Hypertension is a leading cause of morbidity and mortality worldwide. Individuals
      with hypertension are at increased risk of stroke, heart disease and kidney
      failure. Both genetic and lifestyle factors, particularly diet, have been
      attributed an important role in the development of hypertension. Reducing dietary
      sugar and salt intake can help lower blood pressure; similarly, adequate protein
      intake may also attenuate hypertension. Observational, cross-sectional and
      longitudinal epidemiological studies, and controlled clinical trials, have
      documented significant inverse associations between protein intake and blood
      pressure. Human and animal studies have shown that specific amino acids within
      proteins may have antihypertensive effects. Cysteine, glutathione (a tripeptide),
      glutamate and arginine attenuate and prevent alterations that cause hypertension
      including insulin resistance, decreased nitric oxide bioavailability, altered
      renin angiotensin system function, increased oxidative stress and formation of
      advanced glycation end products. Leucine increases protein synthesis in skeletal
      muscle and improves insulin resistance by modulating hepatic gluconeogenesis.
      Taurine and tryptophan attenuate sympathetic nervous system activity. Soy protein
      helps lower blood pressure through its high arginine content and antioxidant
      activity exhibited by isoflavones. A diet containing an ample amount of protein
      may be a beneficial lifestyle choice for individuals with hypertension; one
      example is the Dietary Approaches to Stop Hypertension (DASH) diet, which is low
      in salt and saturated fat; includes whole grains, lean meat, poultry, fish and
      nuts; and is rich in vegetables, fruits and low-fat dairy products, which are
      good sources of antioxidant vitamins, minerals and fibre. Including an adequate
      supply of soy in the diet should also be encouraged.

PMID- 22477582
TI  - On the relation between radical behaviorism and the science of verbal behavior.
AB  - A fully-developed "science of verbal behavior" may depend upon a recognition of
      the implications of Skinner's scientific system, radical behaviorism,
      particularly as it relates to the nature of scientific research. An examination
      of the system and Skinner's own research practices imply, for example, that
      samples of vocal or written verbal behavior collected under controlling
      conditions may be observed as directly for the effects of controlling
      contingencies as in the traditional practice involving cumulative response
      records. Such practices may be defended on the basis of the pragmatic
      epistemology which characterizes radical behaviorism. An example of one type of
      exploratory method is described.

PMID- 22477583
TI  - Lying.

PMID- 22477584
TI  - Rules as classes of verbal behavior: A reply to Glenn.

PMID- 22477585
TI  - On rules and rule-governed behavior: A reply to Catania's reply.

PMID- 22477586
TI  - A review of empirical studies of verbal behavior.
AB  - This paper reviews empirical research which has been directly influenced by
      Skinner's Verbal Behavior. Despite the importance of this subject matter, the
      book has generated relatively little empirical research. Most studies have
      focused on Skinner's mand and tact relations while research focused on the other
      elementary verbal operants has been limited. However, the results of empirical
      research that exist support Skinner's analysis of the distinction between
      elementary verbal operants and his distinction between the speaker's and
      listener's repertoires. Further, research suggests that language training
      programs may not be successful if they do not provide explicit training of each
      elementary verbal operant and independent training of speaker's and listener's
      repertoires.

PMID- 22477587
TI  - Teaching intraverbal behavior to severely retarded children.
AB  - The present study evaluated procedures to teach single and multiple intraverbal
      responses, and assessed whether intraverbals and tacts are functionally
      independent. A delayed echoic prompting procedure was used to assess transfer of
      stimulus control. Probes were interspersed among intraverbal training trials to
      measure the emergence of intraverbals that were not directly trained. Following
      intraverbal training, visual stimuli were presented to determine whether response
      topographies transferred to tact conditions. The results suggest that special
      training is necessary for the acquisition of intraverbal responding in retarded
      individuals, and provide some support for the functional independence of
      intraverbals and tacts at the time of acquisition.

PMID- 22477588
TI  - Effects of oral reading rate and inflection on intraverbal responding.
AB  - Reading comprehension may be defined as a type of intraverbal responding. Only a
      few studies have reported the effects of the rate and inflection of oral reading
      performances on this class of intraverbals. In the present study the effects of
      four conditions; low reading rates (40 to 60 words per minute), with and without
      inflection, and high reading rates (150 to 200 words per minute), with and
      without inflection, were studied using six subjects. Two of the subjects were of
      high school age, reading below grade level, and four were typical third grade
      students, reading on grade level. The results indicated that the combination of
      high oral reading rate with inflection, a condition approximating conversational
      speech, increased both the accuracy and speed of intraverbal responding
      (comprehension), more than any other combination of variables. A second
      experiment was conducted which systematically replicated the findings across
      reading levels, reading passage content, settings, and subjects.

PMID- 22477589
TI  - Low interrater agreement on the semantic base of textual material.
AB  - The present paper describes three experiments which were conducted to determine
      whether independent raters could agree upon the semantic base of textual
      materials. These experiments were occasioned by an earlier experiment in which
      the investigators reported success in increasing the ability of students to
      extract the semantic base from textual materials. The present paper reports our
      unsuccessful attempts to obtain an acceptable level of agreement among
      independent raters about what constituted the semantic base of a number of texts.
      The paper concludes by raising some doubts about the strategy of extending
      behavior-analytic research to verbal behavior by combining behavior-change
      procedures with cognitive constructs.

PMID- 22477590
TI  - Transfer of function across members of an equivalence class.
AB  - A child's presses on response windows behind which stimuli were presented via
      computer monitor occasionally lit lamps arranged in a column; a present was
      delivered when all lamps in the column were lit. During the operation of a
      multiple schedule, the child first learned low rates of pressing in the presence
      of STAR and high rates in the presence of TREE. Later, in an arbitrary matching
      task, the child learned to select STAR given wiggly WORM and TREE given BLOCK.
      When WORM and BLOCK were inserted into the multiple schedule, the low and high
      rates respectively correlated with STAR and TREE transferred to them. Tests of
      reflexivity (identity matching) and of symmetry of the arbitrary matching implied
      that STAR and WORM had become members of one equivalence class, and TREE and
      BLOCK had become members of another.

PMID- 22477591
TI  - Role of methylglyoxal in essential hypertension.
AB  - Altered glucose metabolism due to insulin resistance is a common feature of
      essential hypertension in humans and in animal models. Elevated endogenous
      aldehydes in genetic (spontaneously hypertensive rats) and acquired (fructose
      induced hypertensive rats) models of essential hypertension may be due to
      increased production of the reactive aldehyde methylglyoxal, resulting from
      altered glucose metabolism. Excess methylglyoxal binds sulfhydryl groups of
      membrane proteins, altering calcium channels and increasing cytosolic free Ca(2+)
      and blood pressure. It has been demonstrated that methylglyoxal, when given in
      drinking water to Wistar-Kyoto rats, leads to an increase in kidney aldehyde
      conjugates, cytosolic free Ca(2+) concentration, decreased serum nitric oxide,
      renal vascular hyperplasia and hypertension. N-acetylcysteine (NAC) in the diet
      of these animals prevented hypertension and associated biochemical and
      morphological changes. NAC normalizes blood pressure by directly binding to
      excess methylglyoxal, thus normalizing Ca(2+) channels, cytosolic Ca(2+) and
      nitric oxide. NAC also leads to increased levels of tissue glutathione, a storage
      form of cysteine. Glutathione acts as a cofactor in the enzymatic catabolism of
      methylglyoxal. Cysteine and other antioxidants, such as vitamins B(6), C and E,
      and lipoic acid, prevented hypertension and associated biochemical and
      morphological changes in both genetic and acquired rat models of hypertension.
      The antihypertensive effect of dietary antioxidants may be due to an increase in
      tissue cysteine and glutathione, which improves glucose metabolism and decreases
      tissue methylglyoxal. A diet rich in these antioxidants may be effective in
      preventing and controlling hypertension in humans.

PMID- 22477592
TI  - A comparative study of restenosis rates in bare metal and drug-eluting stents.
AB  - BACKGROUND: Various studies have been performed throughout the world on the rate
      of restenosis using bare metal stents (BMS) and drug-eluting stents (DES). The
      prohibitive costs associated with DES generally dictate the type of stent used,
      especially in developing countries. Therefore, there was a need for a study to
      assess the effect of various risk factors on restenosis in BMS and DES in the
      Indian context. A study was performed in the premier institution of the Indian
      Armed Forces, the Army Hospital (Research and Referral), New Delhi, India, under
      the aegis of the Indian Council of Medical Research (New Delhi). The profile of
      patients in the armed forces is inherently diverse in terms of demography,
      ethnicity, genetics, etc, which reflects the diverse and varied nature of the
      population in India. METHODS AND RESULTS: A total of 130 patients were included
      in the present study. Follow-up after stent implantation was scheduled for six to
      nine months following the procedure to assess symptoms, drug compliance, and
      treadmill test and coronary angiography results, and to ascertain the incidence
      of restenosis. However, only 80 patients returned for follow-up and, therefore,
      the final analysis was based on these patients. They were segregated into BMS
      (n=41) and DES (n=39) groups. Restenosis occurred in 29 patients (36.3%). Nine of
      39 patients with DES (23.1%) and 20 of 41 patients with BMS (48.8%) developed
      restenosis. There was a statistically significant relationship between restenosis
      and female sex, clinical presentation before intervention and at the time of
      follow-up evaluation (unstable angina), hypertension, positive stress test and
      compliance with medical therapy (P<0.05). No statistically significant
      relationship was observed between restenosis and age, diabetes, smoking, obesity
      and diet (P>0.05). CONCLUSIONS: DES appear to reduce the restenosis rate and
      clinical end points, and appear to be more cost effective than BMS. Patient
      related factors (eg, sex, hypertension and unstable angina) are important
      variables that affect the restenosis rate. Noninvasive stress testing had high
      positive and negative predictive values. Therefore, based on the present study,
      noninvasive stress testing is suggested before routine angiography at follow-up,
      which will reduce the need for repeat coronary angiography.

PMID- 22477593
TI  - Evidence for unmyelinated C fibres and inflammatory cells in human varicose
      saphenous vein.
AB  - The physiopathology of venous symptoms, such as pain, leg heaviness or swelling
      sensations, in chronic venous disease (CVD) remains unclear. Localized release of
      proinflammatory mediators appears to play a key role but the presence of
      nociceptors sensitive to inflammatory mediators, such as unmyelinated C fibres,
      needs to be demonstrated. The present study included 10 patients with documented
      CVD who underwent surgery for saphenectomy. For each patient, five segments of
      the great saphenous vein were immunostained with anti-S100 protein and anti-CD45
      to identify nerve fibres and inflammatory cells, respectively. Light microscopy
      was completed by electron microscopy. In all patients, S100 immunopositive nerve
      fibres and CD45 immunopositive cells were observed. Under an electron microscope,
      advanced signs of wall remodelling were systematically observed. The density of
      nerve fibres was low and variable from one sample to another. Unmyelinated C
      fibres were mainly located in the external part of the media and to a lesser
      extent in the internal part of the adventitia. Inflammatory cells, mainly
      histiocytes, were scattered in the media. Mast cells were observed in three
      patients. In conclusion, unmyelinated C fibres and inflammatory cells are present
      in the varicose saphenous vein wall. Their linked roles in symptoms of CVD should
      be further explored.

PMID- 22477594
TI  - Predictors of contractile recovery after revascularization in patients with
      anterior myocardial infarction who received thrombolysis.
AB  - BACKGROUND: Identification of viable myocardium after myocardial infarction has
      gained paramount importance with the current progress in coronary
      revascularization. OBJECTIVE: To explore the prognostic power of certain patient
      characteristics to predict myocardial contractile recovery after
      revascularization in patients presenting with acute anterior ST elevation
      myocardial infarction (STEMI) who received thrombolytic therapy. METHODS: Seventy
      three consecutive patients presenting with first acute anterior STEMI who had
      received thrombolytic therapy and had significant coronary stenosis or occlusion
      of the infarct-related artery amenable for revascularization were enrolled. All
      patients underwent echocardiographic assessment of regional wall motion and left
      ventricular ejection fraction. Patients underwent coronary revascularization by
      either percutaneous angioplasty or surgical bypass. Echocardiography was repeated
      two to three months following revascularization. Patients were classified into
      two groups: group 1 had evidence of contractile recovery after revascularization
      at follow-up echocardiography and group 2 had no such evidence of recovery.
      RESULTS: Predictors of contractile recovery after revascularization included a
      shorter time from symptom onset to the institution of thrombolytic therapy, a
      lower baseline wall motion score index, the presence of grade 3 collaterals to
      the infarct-related artery and the use of beta-blockers. Instead, the presence of
      diabetes mellitus and a totally occluded infarct-related artery predicted poor
      contractile recovery. CONCLUSIONS: Myocardial contractile recovery after
      revascularization in patients presenting with first acute anterior STEMI may be
      predicted by the absence of diabetes, a shorter time from symptom onset to
      thrombolytic therapy, the use of beta-blockers, a lower initial wall motion index
      score and the presence of collaterals to the infarct-related artery.

PMID- 22477595
TI  - Prolongation of QRS duration and axis deviation in the right bundle branch block
      are not markers for left ventricular systolic dysfunction.
AB  - BACKGROUND: Right bundle branch block (RBBB) is not commonly associated with
      structural heart disease and left ventricular (LV) systolic dysfunction. The
      purpose of the present study was to determine whether the QRS duration and degree
      of right axis deviation (RAD) or left axis deviation (LAD) in patients with RBBB
      predicted a subset of patients with significant LV systolic dysfunction. METHODS:
      In the present prospective study, 75 of 200 consecutive patients with RBBB had
      their ejection fraction (EF) evaluated by echocardiography. The relationship
      among QRS duration, axis and EF was derived. RESULTS: There were no significant
      differences in sex and EF among the patients with a normal axis, RAD or LAD. The
      EFs of patients with a normal axis (n=27), RAD (n=15) and LAD (n=33) were 52+/
      15%, 49+/-14% and 46+/-17%, respectively (P=0.35). The mean EF (46+/-16%) of
      patients with a QRS duration of 150 ms or greater (n=53) was not significantly
      different from the mean EF (49+/-18%) of patients with a QRS duration of less
      than 150 ms (n=22) (P=0.54). For patients with a QRS of 120 ms or greater and
      less than 150 ms (n=22), QRS of 150 ms or greater and 180 ms or less (n=48), and
      QRS of greater than 180 ms (n=5), the mean EFs were 49+/-18%, 47+/-16% and 44+/
      7%, respectively (P=0.78). There was no significant correlation between QRS
      duration and EF in all patients (r=0.03, P=0.83), EF and RAD (r=0.38, P=0.16) or
      EF and LAD (r=0.26, P=0.14). CONCLUSIONS: In patients with RBBB, the QRS duration
      and axis do not have a significant relationship with EF. Furthermore,
      prolongation of the QRS duration (150 ms or greater) in the presence of RBBB is
      not a marker of significant LV systolic dysfunction.

PMID- 22477596
TI  - A novel method to quantify carotid artery stenosis by Doppler ultrasound: Using
      the continuity principle.
AB  - BACKGROUND AND PURPOSE: A novel method to quantify carotid artery stenosis by
      using the continuity principle was evaluated. It was hypothesized that the novel
      method improved the accuracy of carotid ultrasound in assessing carotid artery
      stenosis. METHODS: Forty-nine patients were retrospectively studied. They were at
      a high risk for stroke and myocardial infarction, with significant cardiovascular
      risk factors. They were studied by carotid ultrasound as well as by one of the
      accepted gold standard techniques (computed tomography, magnetic resonance
      imaging or angiography). The cross-sectional areas of the narrowed part of the
      carotid arteries were measured using the continuity principle, and the percentage
      stenosis was thus calculated. RESULTS: The analyses showed that the combination
      of the conventional and novel criteria (ie, classifying a case as significant
      only if its stenosis was 67% or greater and its peak systolic velocity was 130
      cm/s or greater) conferred the highest accuracy in predicting significant carotid
      stenosis compared with the gold standard techniques. CONCLUSION: From a practical
      point of view, the combined criteria might be useful for improving the accuracy
      of carotid ultrasound in predicting significant carotid stenosis.

PMID- 22477597
TI  - Providing insights into atherosclerosis: A case of multivessel coronary artery
      disease with an anomalous straightforward vessel spared from atherosclerosis.
AB  - Atherosclerotic plaques tend to involve arterial localizations in which blood
      flow is not laminar due to arterial bends and bifurcations. A 49-year-old man was
      admitted to hospital with breathlessness and was subsequently diagnosed with left
      ventricular failure. Coronary angiography revealed three-vessel coronary artery
      disease and an anomalous extra left anterior descending artery taking off from
      the right sinus of Valsalva and spared from atherosclerosis. The absence of side
      branches and the relative lack of bends in arterial geometry were considered to
      be the cause of resistance to atherosclerosis. The present case identifies local
      flow conditions as an important factor determining the genesis of atherosclerosis
      in arterial segments.

PMID- 22477598
TI  - Letter to the editor.

PMID- 22477599
TI  - An instance of spurious equivalence relations.
AB  - Four normal children learned conditional discriminations that had upper-case or
      lower-case Greek letters as comparison stimuli, and dictated letter names as
      samples. Experimental stimuli were three pairs of letters; within each pair, an
      upper- and a lower-case letter were conditionally related to the same dictated
      sample. Four control stimuli, also upper- and lower-case letters, were each
      conditionally related to a different dictated sample. Conditional-discrimination
      tests for equivalence used the upper- and lower-case letters both as samples and
      comparisons. Untaught conditional relations between the upper- and lower-case
      members of each experimental stimulus pair were expected to emerge on the basis
      of their previously established relations to a common sample. The emergence of
      conditional relations between control stimuli, however, would have suggested an
      artifact. In test trials with the experimental stimuli as samples and
      comparisons, new conditional discriminations emerged as expected with all four
      children. With two of the children, however, consistent discriminations also
      emerged between control stimuli. Evidence suggested that uncontrolled features of
      the program for teaching the children the baseline conditional discriminations
      might have been responsible for the emergence of untaught conditional relations.

PMID- 22477600
TI  - Do stimulus classes exist before they are tested?
AB  - This paper addresses verbal practices that are common when behavior analysis talk
      about stimulus classes. Specifically, we examine some of the conditions that may
      set the occasion for saying "Stimulus classes exist prior to the tests that
      document their formation." We suggest that "stimulus class" should tact behavior
      that is a function of training and test procedures, not entities that "form" or
      "exist" in any independent sense. To frame our arguments, we review relevant
      research findings and suggest descriptive language that is more consistent with
      behavior analytic traditions.

PMID- 22477601
TI  - Equivalence class formation in non-hearing impaired children and hearing impaired
      children.
AB  - THE RELATIONSHIP BETWEEN VERBAL BEHAVIOR AND STIMULUS EQUIVALENCE WAS EXAMINED
      USING THREE SETS OF CHILDREN DIFFERING IN CHRONOLOGICAL AGE AND VERBAL ABILITY:
      (1) non-hearing impaired three and four year olds who had verbal skills generally
      consistent with their chronological ages; (2) partially hearing (severe to
      profoundly deaf) children who were rated with verbal ages of above 2 years; and
      (3) partially hearing children (also severely to profoundly deaf) who were rated
      with verbal ages of below 2 years. All children were taught a series of four
      conditional discriminations using unfamiliar stimuli. The children were then
      tested to determine whether classes of equivalent stimuli had formed. Although
      all the children were able to learn the conditional discriminations equally well
      and all the verbally-able children (normal and partially hearing) formed
      equivalence classes, only one of the verbally-impaired children reliably
      demonstrated stimulus equivalence formation. These results are consistent with
      the suggestion that stimulus equivalence and human verbal behavior are closely
      related.

PMID- 22477602
TI  - Comparing topography-based verbal behavior with stimulus selection-based verbal
      behavior.
AB  - Michael (1985) distinguished between two types of verbal behavior: topography
      based and stimulus selection-based verbal behavior. The current research was
      designed to empirically examine these two types of verbal behavior while
      addressing the frequently debated question, Which augmentative communication
      system should be used with the nonverbal developmentally disabled person? Four
      mentally retarded adults served as subjects. Each subject was taught to tact an
      object by either pointing to its corresponding symbol (selection-based verbal
      behavior), or making the corresponding sign (topography-based verbal behavior).
      They were then taught an intraverbal relation, and were tested for the emergence
      of stimulus equivalence relations. The results showed that signed responses were
      acquired more readily than pointing responses as measured by the acquisition of
      tacts and intraverbals, and the formation of equivalence classes. These results
      support Michael's (1985) analysis, and have important implications for the design
      of language intervention programs for the developmentally disabled.

PMID- 22477603
TI  - Nonverbal behavior correlated with the shaped verbal behavior of children.
AB  - Children under 6 years old pressed on response windows behind which stimuli
      appeared (star or tree). Presses occasionally lit lamps arranged in a column; a
      present was delivered when all lamps were lit. A random-ratio schedule in the
      presence of star alternated with a random-interval schedule in the presence of
      tree. These contingencies usually did not produce respective high and low
      response rates in the presence of star and tree, but the shaping of verbal
      behavior (e.g., "press a lot without stopping" or "press and wait") was sometimes
      accompanied by corresponding changes in response rate. Verbal shaping was
      accomplished between schedule components during verbal interactions between the
      child and a hand-puppet, Garfield the Cat, and used social consequences such as
      enthusiastic reactions to what the child had said as well as concrete
      consequences such as delivery of extra presents. Variables that may constrain the
      shaping of verbal behavior in children seem to include the vocabulary available
      to the child and the functional properties of that vocabulary; the correlation
      between rates of pressing and what the child says about them may depend upon such
      variables.

PMID- 22477604
TI  - Reinforcement, stereotypy, and rule discovery.
AB  - The effects of reinforced pretraining on subsequent rule discovery were examined
      with college students as subjects. Levels of behavioral stereotypy observed
      during reinforced and non-contingent pretraining were compared. During
      pretraining subjects received reinforcement if they pressed two keys in a
      particular sequence. During the problem session pressing each key four times was
      a necessary condition for reinforcement, but each problem had additional
      different requirements for reinforcement. Subjects were asked to solve the
      problems by discovering the rule that determined whether or not they received
      reinforcement. Levels of stereotyped responding during pretraining were
      equivalent for contingently and non-contingently trained subjects. During the
      problem session contingently pretrained, non-contingently pretrained, and naive
      subjects required equal numbers of trials to solve problems and solved the same
      number of problems. The results suggest that behavioral stereotypy observed in
      this experimental preparation may be due to repeated exposure to the task.
      Differences between the results observed in this study and that of Schwartz
      (1982) and implications for the use of reinforcement procedures in applied
      settings are discussed.

PMID- 22477605
TI  - "I'll do it when the snow melts": The effects of deadlines and delayed outcomes
      on rule-governed behavior in preschool children.
AB  - This study examined the control exerted by different types of rules on the
      behavior of preschool children. Four similar rules were presented to eight, four
      year-old children, using a multielement design. The contingencies the rules
      described varied in the specification of deadlines and in the delays in the
      delivery of the reinforcers. The results showed (a) rules specifying only
      response requirements did not reliably control behavior, (b) rules specifying an
      immediate deadline with the immediate delivery of a reinforcer exerted reliable
      control, (c) rules specifying an immediate deadline with a one-week delay in the
      delivery of the reinforcer also exerted reliable control, and (d) rules
      specifying no deadline with a one-week delay in the delivery of the reinforcer
      exerted little control. These results suggest that a rule's specification of a
      deadline is crucial in its control of behavior, but the delay of the reinforcer
      is of little importance. This latter conclusion further suggests that problems in
      self-control do not result from delayed outcomes or the inablity to delay
      gratification, contrary to conventional wisdom.

PMID- 22477606
TI  - A reply to behavior analysts writing about rules and rule-governed behavior.
AB  - Verbal stimuli called "rules" or "instructions" continue to be interpreted as
      discriminative stimuli despite recent arguments against this practice. Instead,
      it might more fruitful for behavior analysts to focus on "contingency-specifying
      stimuli" which are function-altering. Moreover, rather than having a special
      term, "rule," for verbal stimuli whose only function is discriminative, perhaps
      behavior analysts should reserve the term, if at all, only for these function
      altering contingency-specifying stimuli.

PMID- 22477607
TI  - The acquisition of tacts, mands, and intraverbals by individuals with traumatic
      brain injury.
AB  - Two individuals who sustained traumatic brain injuries from motorcycle accidents
      were taught several verbal responses by using tact, mand, and intraverbal
      training procedures. The rate of acquisition for each operant and the transfer to
      untrained verbal operants involving the same response topography were measured.
      The results showed that tacts and intraverbals were acquired quickest, and
      training on the tact produced the greatest amount of transfer to the untrained
      verbal operants. Intraverbal training also resulted in transfer for both
      subjects, but to varying degrees. Direct mand training proved to be the least
      efficient way to generate a mand repertoire, and when acquired showed least
      amount of transfer to the untrained operants. These results seem to be in
      contrast with the findings of similar research with developmentally disabled
      individuals, and may have implications for methods of language instruction for
      the brain injured population.

PMID- 22477608
TI  - A description of teacher-student verbal interactions in a resource room versus
      regular classrooms.
AB  - The focus of this study was the description and classification of verbal operants
      as described by Skinner (1957) that were used by a resource room teacher and two
      regular education teachers, the compliance responses of two students identified
      as learning disabled who attended all three classes, and the actual tasks that
      existed in each setting. These descriptions were used to compare the similarities
      and differences that may account for student success in a resource classroom and
      lack of success in mainstream classrooms. The results indicated that the verbal
      operants could be used to determine the tasks that existed in each setting.
      Comparisons showed that the greatest differences among the settings existed in
      the type of "mand" stated, the proportion of instructional to management "mands,"
      the frequency of compliance to instructional "mands," and the teacher consequence
      for compliance or non-compliance with "mands."

PMID- 22477609
TI  - Establishing verbal repertoires: Toward the application of general case analysis
      and programming.
AB  - A great deal of clinical and experimental work in past decades has focused on
      establishing functional verbal repertoires that are used across various settings
      and situations by persons with moderate and severe disabilities. Such work has
      not always involved a careful analysis and programming approach for structuring
      training to achieve the desired range of stimulus control relationships. General
      case analysis and programming procedures, which are based on behavior analytic
      and Direct Instruction principles and techniques, have proven effective in recent
      years for teaching a variety of community-based skills to learners with moderate
      and severe disabilities. This paper outlines the general case process and
      discusses its application to establish verbal repertoires.

PMID- 22477610
TI  - On the relationship between speech and writing with implications for behavioral
      approaches to teaching literacy.
AB  - Two theories of the relationship between speech and writing are examined. One
      theory holds that writing is restricted to a one-way relationship with speech-a
      unidirectional influence from speech to writing. In this theory, writing is
      derived from speech and is simply a representation of speech. The other theory
      holds that additional, multidirectional influences are involved in the
      development of writing. The unidirectional theory focuses on correspondences
      between speech and writing while the multidirectional theory directs attention to
      the differences as well as the similarities between speech and writing. These
      theories have distinctive pedagogical implications. Although early behaviorism
      may be seen to have offered some support for the unidirectional theory, modern
      behavior analysis should be seen to support the multidirectional theory.

PMID- 22477611
TI  - Understanding and the listener: Conflicting views.
AB  - Skinner's (1957, 1974) distinction between three senses of the term understanding
      is presented. For Skinner, a listener understands if she (a) can repeat back to
      the speaker what he has said; or (b) can respond appropriately; or (c) knows
      about the controlling variables. Next, a critique of Skinner's view by Parrott
      (1984; now L.J. Hayes) is presented. Parrott criticizes the first sense of
      understanding for simplifying a complex activity; the second for equating
      understanding with reinforcement mediation; and the third for defining
      understanding as potential behavior. Next, Parrott's two alternative views are
      presented. Understanding is (a) having perceptual responses of things when only
      their "names" are present, and (b) organizing objects and words into relational
      networks. Lastly, Skinner's and Parrott's views on understanding are evaluated,
      and Parrott's views are critiqued.

PMID- 22477612
TI  - Verbal behavior and the history of linguistics.
AB  - A recent paper by a historian of linguistics suggests that after many years of
      neglect linquists are finding value in the analysis of verbal behavior developed
      by B.F. Skinner.

PMID- 22477613
TI  - Continuous monitoring of cerebrovascular reactivity using pulse waveform of
      intracranial pressure.
AB  - BACKGROUND: Guidelines for the management of traumatic brain injury (TBI) call
      for the development of accurate methods for assessment of the relationship
      between cerebral perfusion pressure (CPP) and cerebral autoregulation and to
      determine the influence of quantitative indices of pressure autoregulation on
      outcome. We investigated the relationship between slow fluctuations of arterial
      blood pressure (ABP) and intracranial pressure (ICP) pulse amplitude (an index
      called PAx) using a moving correlation technique to reflect the state of cerebral
      vasoreactivity and compared it to the index of pressure reactivity (PRx) as a
      moving correlation coefficient between averaged values of ABP and ICP. METHODS: A
      retrospective analysis of prospective 327 TBI patients (admitted on neurocritical
      care unit of a university hospital in the period 2003-2009) with continuous ABP
      and ICP monitoring. RESULTS: PAx was worse in patients who died compared to those
      who survived (-0.04 +/- 0.15 vs. -0.16 +/- 0.15, chi2 = 28, p < 0.001). In
      contrast to PRx, PAx was able to differentiate between fatal and non-fatal
      outcome in a group of 120 patients with ICP levels below 15 mmHg (-0.04 +/- 0.16
      vs. -0.14 +/- 0.16, chi2 = 6, p = 0.01). CONCLUSIONS: PAx is a new modified index
      of cerebrovascular reactivity which performs equally well as established PRx in
      long-term monitoring in severe TBI patients, but importantly is potentially more
      robust at lower values of ICP. In view of establishing an autoregulation-oriented
      CPP therapy, continuous determination of PAx is feasible but its value has to be
      evaluated in a prospective controlled trail.

PMID- 22477616
TI  - Latest drug developments in the field of cardiovascular disease.
AB  - Cardiovascular disease has been responsible for more deaths annually than any
      other disease category since 1900, except for the influenza epidemic in 1916.
      Yet, the drug pipeline has been largely bereft of new entrants. In 2008, one new
      cardiovascular medication was marketed in the United States. In 2009, there were
      two new cardiovascular medications. In comparison, there were seven new drugs for
      oncology in 2009. The present review explores new agents within the context of
      models currently in the drug pipeline. Of course, there is no guarantee that any
      of these agents will be marketed. A discussion of the models is illustrative of
      the types of approaches being used to develop new cardiovascular agents.

PMID- 22477617
TI  - The impact of severe distal left main disease on target lesion revascularization
      in patients with trifurcating coronary artery disease receiving the paclitaxel
      drug-eluting stent.
AB  - BACKGROUND: The presence of severe left main (LM) disease has been shown to
      adversely influence the outcome of patients undergoing percutaneous treatment of
      bifurcating LM disease. LM trifurcating coronary artery disease (LMTCAD) is even
      more complex and challenging to treat. The present article reports on the
      immediate and midterm outcomes of patients with severe LM disease treated with
      the paclitaxel drug-eluting stent for LMTCAD. METHODS: Consecutive patients
      (n=52) who underwent LM trifurcating stenting with the paclitaxel drug-eluting
      stent at the Genesis Medical Center (Iowa, USA) over a two-year period were
      divided into two groups: type A (with severe [50% or greater] LM involvement
      including trifurcating branches) and type B (with no LM involvement but involving
      the trifurcating branches). Demographic, clinical, procedural and midterm
      clinical outcomes were reviewed. Angiograms were analyzed by an operator who was
      blinded to patient histories. The primary end point of the study was target
      lesion revascularization (TLR) on follow-up. Descriptive and univariate analyses
      were performed, and survival curves were plotted to compare the two groups.
      RESULTS: Demographic and clinical variables were identical in both groups. Type A
      lesions required significantly more stents to treat than type B lesions (4.13+/
      1.78 versus 2.33+/-1.22; P=0.001). The techniques to treat both lesions were
      considerably different, with more V stenting in type B and more Y stenting in
      type A. The TLR rate was 64.3% in type A versus 18.2% in type B (P=0.005). On
      follow-up, one patient with type B disease had sudden death, possibly related to
      stent thrombosis. CONCLUSION: Severe LM disease has a significant adverse impact
      on TLR in patients with LMTCAD. Given the high TLR rate, bypass surgery needs to
      be considered as first-line therapy in patients with type A trifurcating coronary
      artery disease.

PMID- 22477615
TI  - Active surveillance for favorable-risk prostate cancer: background, patient
      selection, triggers for intervention, and outcomes.
AB  - With the advent of increasingly sensitive and widely used diagnostic testing,
      cancer overdiagnosis in particular has emerged as a problem in multiple organ
      sites. This has the greatest ramifications in the case of prostate cancer because
      of the very high incidence of latent prostate cancer in aging men, the
      availability of the prostate-specific antigen (PSA) test, and the long-term
      effects of definitive therapy. The condition of most men with favorable-risk
      prostate cancer is far removed from the consequences of a rampaging, aggressive
      disease. Most of these men are not destined to die of their disease, even in the
      absence of treatment. Unfortunately, most of these patients are treated radically
      and are exposed to the risk of significant side effects. Therefore, a selective
      approach to treatment is appealing. The concept is to identify the subset that
      harbor more aggressive disease early enough that curative therapy is still a
      possibility, thereby allowing the others to enjoy improved quality of life, free
      from the side effects of treatment. This review article summarizes the evidence
      supporting active surveillance, and the current approach to this management
      strategy, including the roles of serial biopsy, PSA kinetics, and MR imaging.

PMID- 22477618
TI  - A rare cause of venous thrombosis: Congenital absence (agenesis) of the inferior
      vena cava.
AB  - Deep vein thrombosis is a frequent finding in otherwise healthy, young adults who
      are diagnosed with congenital absence (agenesis) of the inferior vena cava - a
      rare anomaly. This condition is best diagnosed by computed tomography angiography
      with venous phase imaging, and is managed using anticoagulation, percutaneous
      catheter-directed mechanical thrombectomy and thrombolysis. To illustrate this
      phenomenon, a case is presented.

PMID- 22477619
TI  - Arteritic anterior ischemic optic neuropathy treated with intravenous
      prostaglandin E(1) and steroids.
AB  - Arteritic anterior ischemic optic neuropathy (AAION) is an acute ischemia of the
      posterior ciliary arteries and/or ophthalmic artery due to inflammation. Therapy
      is immediate intervention with systemic steroids, especially to protect against
      vision loss in the other eye. The addition of a potent vasodilator to the
      steroids could help restore ocular blood flow and improve visual acuity. The
      objective of the current report was to present the use of prostaglandin E(1)
      (PGE(1)) - a powerful vasodilator of the microcirculation - in the treatment of
      AAION. Two patients with AAION were treated with intravenous steroids and PGE(1).
      The visual acuity improved from 4/50 (less than 20/200) to 6/10 (20/35) in one
      patient and from 1/50 (20/400) to 1/10 (20/200) in the second patient. The visual
      fields in both patients maintained small central islands of vision. No
      complications due to the use of PGE(1) were seen. Intravenous PGE(1) should be
      considered in addition to steroids in cases of AAION to immediately restore blood
      flow to the optic nerve and improve visual acuity while the steroids reduce the
      inflammation.

PMID- 22477620
TI  - Bilateral massive pulmonary thromboembolism in a young patient treated with
      supportive measures and an inferior vena cava filter with excellent outcome.
AB  - Acute pulmonary embolism (PE) is a common and often fatal disease with a
      mortality rate of more than 30% in untreated patients. There is a twofold
      increase in mortality in patients with massive PEs who do not receive treatment.
      Recurrent embolism is the most common cause of death. A 48-year-old woman
      presented to Tan Tock Seng Hospital, Singapore, on December 16, 2009, with a
      massive pulmonary thromboembolism. She was admitted to the intensive care unit
      and treated with supportive measures, ventilatory support, antibiotics and
      ionotropes. The patient was diagnosed with urosepsis with septicemic shock,
      disseminated intravascular coagulation, acute renal failure, high anion gap
      metabolic acidosis, iron-deficiency anemia secondary to menorrhagia, and a
      uterine mass with high cancer antigen 125, although malignancy was ruled out.
      Anticoagulation or thrombolysis could not be provided in view of coagulopathy.
      The patient subsequently underwent inferior vena cava filter insertion on
      December 31, 2009. The patient showed clinical improvement over the next two
      weeks with antibiotics and supportive measures. If there is a contraindication to
      anticoagulation or thrombolysis, massive pulmonary thromboembolism should be
      treated aggressively with supportive measures. Inferior vena cava filter
      insertion should be instituted early to prevent recurrent PE, which can be fatal.
      It may take weeks before the patient displays clinical improvement.

PMID- 22477621
TI  - Metabolic syndrome, peripheral vascular disease and coronary artery disease: A
      concise review.
AB  - Metabolic syndrome has a very strong association with both forms of
      cardiovascular (CV) disease - coronary artery disease and peripheral vascular
      disease. There is also a marked interrelationship between the two forms of CV
      disease. When one form of CV disease is present, the other should be strongly
      suspected and the possible occurrence of associated vascular events should be
      clinically evaluated. When three of the five major components that define
      metabolic syndrome are present, the clinical evidence indicates that one or both
      forms of CV disease are present, at least in incipient form. To give maximum
      clinical benefit to the patient at risk, the clinician must be aware of these
      associations, look for them and institute the measures that can reduce the risk
      of progression.

PMID- 22477623
TI  - Retinal optical coherence tomography manifestations of intraocular lymphoma.
AB  - PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare disease. The
      index report describes a patient with intraocular lymphoma secondary to recurrent
      PCNSL and corresponding retinal findings on spectral domain optical coherence
      tomography (SD-OCT). METHODS: Case report. RESULTS: OCT changes were documented
      and correlated with the clinical course of intraocular lymphoma progression in
      the index patient. The OCT changes, manifested as hyperreflective material
      accumulation in the intraretinal and subretinal pigment epithelial spaces, were
      caused by lymphomatous infiltration. CONCLUSION: SD-OCT can be useful in
      diagnosing and monitoring the progression or regression of intraocular lymphoma
      with retinal involvement.

PMID- 22477622
TI  - Protein refolding in peroxisomes is dependent upon an HSF1-regulated function.
AB  - Post-heat shock refolding of luciferase requires chaperones. Expression of a
      dominant negative HSF1 mutant (dnHSF1), which among other effects depletes cells
      of HSF1-regulated chaperones, blocked post-heat shock refolding of luciferase
      targeted to the cytoplasm, nucleus, or peroxisomes, while refolding of
      endoplasmic reticulum (ER)-targeted luciferase was inhibited by about 50 %.
      Luciferase refolding in the cytoplasm could be partially restored by expression
      of HSPA1A and fully by both HSPA1A and DNAJB1. For full refolding of ER
      luciferase, HSPA1A expression sufficed. Neither nuclear nor peroxisomal refolding
      was rescued by HSPA1A. A stimulatory effect of DNAJB1 on post-heat shock
      peroxisomal luciferase refolding was seen in control cells, while refolding in
      the cytoplasm or nucleus in control cells was inhibited by DNAJB1 expression in
      the absence of added HSPA1A. HSPB1 also improved refolding of peroxisomal
      luciferase in control cells, but not in dnHSF1 expressing cells. HSP90, HSPA5,
      HSPA6, and phosphomevalonate kinase (of which the synthesis is also downregulated
      by dnHSF1) had no effect on peroxisomal refolding in either control or chaperone
      depleted cells. The chaperone requirement for post-heat shock refolding of
      peroxisomal luciferase in control cells is thus unusual in that it can be
      augmented by DNAJB1 or HSPB1 but not by HSPA1A; in dnHSF1 expressing cells,
      expression of none of the (co)-chaperones tested was effective, and an as yet to
      be identified, HSF1-regulated function is required.

PMID- 22477624
TI  - Nontuberculous mycobacterial infection after frontalis sling surgery using
      silicone rod.
AB  - PURPOSE: The purpose of this study is to report a case of nontuberculous
      mycobacterial infection after frontalis sling surgery. METHOD: A 65-year-old man
      presented with bilateral painful, erythematous lesions in the brow and upper
      eyelids. He had a history of frontalis sling surgery for myopathic ptosis 2 years
      back and all lesions were found localized to the tract of the silicone rod used
      in the previous frontalis sling surgery. RESULT: Incision and drainage of the
      lesions with microbiological analysis revealed significant growth of coagulase
      negative staphylococcus and Mycobacterium fortuitum. Sensitivity-based antibiotic
      treatment with intravenous amikacin was started, but poor response necessitated
      eventual explantation of both silicone rods for relief of symptoms. Culture of
      the explanted rods revealed similar results of M. fortuitum infection. Five
      months after the acute presentation, the patient is asymptomatic. CONCLUSION:
      Nontuberculous mycobacterial infection may be a delayed onset complication in
      frontalis sling surgery using silicone rods.

PMID- 22477625
TI  - Topography-based and selection-based verbal behavior: A further comparison.
AB  - Michael (1985) identified two types of verbal behavior, topography-based (e.g.,
      speaking or using sign language) and selection-based (e.g., using a symbol
      board). Sundberg and Sundberg (1990) and Wraikat (1990) compared these systems in
      terms of the ease of learning object naming (tact) and giving the correct sign or
      pointing to the correct symbol on hearing the object name (intraverbal). Sundberg
      and Sundberg (1990) also compared them for the spontaneous development of a new
      relation, identifying the object when hearing its name (stimulus class formation
      or equivalence). The results of both studies favored the topography-based system,
      but in each case some subjects were not verbally skillful enough to learn either
      system and some learned both too easily to permit a useful comparison. The
      current study replicated the two previous ones by teaching the same two verbal
      relations and testing for the emergence of new relations, but adjusted the task
      to the subject's level of functioning during the experiment. This was
      accomplished by varying the number of object relations being learned, and by
      interspersing already learned tasks with the training of new tasks. As with the
      earlier studies, topography-based verbal behavior was easier to learn, and led to
      more new stimulus-class relations than selection-based verbal behavior. These
      data confirm the relevant theoretical analysis, and have practical implications
      for a change in current language training practices.

PMID- 22477626
TI  - The effects of specific versus nonspecific reinforcement on verbal behavior.
AB  - The current study is a systematic replication and extension of previous research
      on the differences between specific (mand) and nonspecific (tact) reinforcement.
      The focus was on the role that these different consequences played in the
      acquisition of verbal behavior. Using both a within-subject and a between
      subjects design, the current researchers trained eight essentially nonverbal
      individuals to tact a variety of foods under two different reinforcement
      conditions. The results showed no significant differences between the four
      matched-pairs in rates of acquisition, or in the resistance to extinction.
      However, subjects in the specific reinforcement condition emitted more untrained
      mand-compliance responses, while subjects in the nonspecific group demonstrated
      increased generalization to multiply controlled mand conditions. The results
      supported previous findings which indicated that the two types of consequences
      were equally effective in the acquisition of tacting, but each had unique
      features and implications for language training with nonverbal populations.

PMID- 22477627
TI  - A descriptive analysis of family discussions about everyday problems and
      decisions.
AB  - Skinner's Verbal Behavior (1957) and "An operant analysis of problem solving"
      (1966) were used to develop a coding system to analyze the relationships between
      verbal behaviors in family problem solving discussions. Taking solution
      statements as a target behavior, sequential relationships were examined with both
      subsequent and antecedent verbal behaviors, comparing families with higher and
      lower rates of solution statements. Results indicated that two categories of
      verbal behavior occurred both subsequent and antecedent to solution statements
      more frequently in families with higher frequencies of solution statements:
      Agreements and contingency statements. Results are discussed in terms of an
      operant theory of problem solving in which agreements may serve as reinforcers
      for solutions and contingency statements may serve as discriminative stimuli.

PMID- 22477628
TI  - Maximization of reinforcement by two autistic students with accurate and
      inaccurate instructions.
AB  - The present study examines maximization of reinforcement by two autistic
      individuals under conditions of no instructions, accurate instructions, and
      inaccurate instructions. Accuracy of instructions and magnitude of reinforcement
      for differential responding in a choice paradigm were systematically varied
      across phases. Subject one maximized reinforcement across all three conditions in
      seven experimental phases. Subject two maximized across these same seven phases,
      but also experienced three additional phases. In two of the additional phases,
      subject two maximized reinforcement. In a ninth phase, when reinforcement was
      intermittent rather than continuous, he failed to maximize reinforcement.
      Implications of the results for the controversies surrounding the concept of rule
      governed behavior are discussed.

PMID- 22477629
TI  - A standard methodology for the analysis, recording, and control of verbal
      behavior.
AB  - Lack of a standard methodology has been one of the major obstacles preventing
      advancement of behavior analytic research in verbal behavior. This article
      presents a standard method for the analysis, recording, and control of verbal
      behavior that overcomes several major methodological problems that have hindered
      operant research in verbal behavior. The system divides all verbal behavior into
      four functional response classes, correct, error, no response, and inappropriate
      behavior, from which all vocal responses of a subject may be classified and
      consequated. The effects of contingencies of reinforcement on verbal operants
      within each category are made immediately visible to the researcher as changes in
      frequency of response. Incorporating frequency of response within each category
      as the unit of response allows both rate and probability of verbal response to be
      utilized as basic dependent variables. This method makes it possible to record
      and consequate verbal behavior in essentially the same way as any other operant
      response. It may also facilitate an experimental investigation of Skinner's
      verbal response categories.

PMID- 22477630
TI  - Quantified trends in the history of verbal behavior research.
AB  - The history of scientific research about verbal behavior research, especially
      that based on Verbal Behavior (Skinner, 1957), can be assessed on the basis of a
      frequency and celeration analysis of the published and presented literature. In
      order to discover these quantified trends, a comprehensive bibliographical
      database was developed. Based on several literature searches, the bibliographic
      database included papers pertaining to verbal behavior that were published in the
      Journal of the Experimental Analysis of Behavior, the Journal of Applied Behavior
      Analysis, Behaviorism, The Behavior Analyst, and The Analysis of Verbal Behavior.
      A nonbehavioral journal, the Journal of Verbal Learning and Verbal Behavior was
      assessed as a nonexample comparison. The bibliographic database also included a
      listing of verbal behavior papers presented at the meetings of the Association
      for Behavior Analysis. Papers were added to the database if they (a) were about
      verbal behavior, (b) referenced B.F. Skinner's (1957) book Verbal Behavior, or
      (c) did both. Because the references indicated the year of publication or
      presentation, a count per year of them was measured. These yearly frequencies
      were plotted on Standard Celeration Charts. Once plotted, various celeration
      trends in the literature became visible, not the least of which was the greater
      quantity of verbal behavior research than is generally acknowledged. The data
      clearly show an acceleration of research across the past decade. The data also
      question the notion that a "paucity" of research based on Verbal Behavior
      currently exists. Explanations of the acceleration of verbal behavior research
      are suggested, and plausible reasons are offered as to why a relative lack of
      verbal behavior research extended through the mid 1960s to the latter 1970s.

PMID- 22477631
TI  - 301 research topics from Skinner's book verbal behavior.
AB  - Skinner's (1957) analysis of verbal behavior addresses some of the most important
      issues in human behavior. However, relatively few of the analyses presented by
      Skinner in Verbal Behavior have been subjected to an experimental analysis. The
      current list of topics was assembled in an effort to stimulate empirical research
      on verbal behavior. The list contains thirty research areas with ten topics
      suggested for each area. A final topic, education, is presented as a challenge to
      behavior analysts.

PMID- 22477632
TI  - A retrospective appreciation of Willard Day's contributions to radical
      behaviorism and the analysis of verbal behavior.
AB  - Willard Day's contributions to radical behaviorism are grouped under three
      headings: (a) an emphasis on the distinction between radical and methodological
      behaviorism; (b) an emphasis on the interpretation, rather than the prediction
      and control, of behavior; and (c) an emphasis on the analysis of verbal behavior
      as a natural, ongoing phenomenon. The paper suggests that the contributions above
      are listed in ascending order of significance.

PMID- 22477633
TI  - A poem for an organism alone.

PMID- 22477634
TI  - The relationship between stimulus equivalence and verbal behavior.
AB  - Despite the apparent similarity between stimulus equivalence and verbal behavior,
      these phenomena have been described in different terms. With different
      terminologies for each phenomenon, the precise nature of their relationship is
      difficult to determine. To explore this relationship, this paper first defines
      stimulus equivalence using a synthesis of the mathematical definition of the
      equivalence relation and Sidman and Tailby's (1982) definition. Selected examples
      of stimulus equivalence are then described as verbal behavior using Skinner's
      (1957) terminology. The paper then cites instances of verbal behavior that cannot
      be described as stimulus equivalence and considers whether there are instances of
      stimulus equivalence that cannot be described as verbal behavior.

PMID- 22477635
TI  - Joint control and the generalization of selection-based verbal behavior.
AB  - Although the acquisition of selection-based verbal behavior can be ascribed to
      the acquisition of a conditional discrimination, such an account cannot explain
      any generalization of the behavior to novel verbal stimuli. The problem is that
      printed and spoken words and phrases do not vary on continuous dimensions that
      would support stimulus generalization. Both conceptual analysis and empirical
      evidence suggest that an alternate form of stimulus control, joint control, can
      more readily account for acquisition and generalization of these performances.
      The fact that joint control depends on topography-based behavior implies that
      generalized selection-based behavior is not an alternative to topography-based
      behavior but depends on its prior development.

PMID- 22477636
TI  - Rule-governed behavior: Unifying radical and paradigmatic behaviorism.
AB  - Commonalities and differences between Skinner's analysis of verbal behavior and
      the paradigmatic behaviorism (PB) approach are described as a means of
      introducing the latter to behavior analysis. The focus is on treating the topic
      of rule-governed behavior-a topic of current interest in behavior analysis in
      addressing the challenge of cognitive psychology-within the PB framework. Dealing
      behaviorally with traditional psychology interests is considered important in PB,
      and this article aims to advance toward that goal. PB has presented a framework
      that deals with not only the behavioral description of language but also with
      language function as well as language acquisition. This includes a treatment of
      the manner in which verbal stimuli generally can control motor behavior. This
      framework includes analyses in addition to those present in the behavior analytic
      framework, along with empirical developments, and these can be used to enhance a
      behavioral understanding of important parts of verbal behavior and the effects of
      verbal stimuli on behavior, including rule-governed phenomena. Our purpose is to
      use the particular topic of rule-governed behavior to argue that a more explicit
      interaction between radical and paradigmatic behaviorism would advance
      behaviorism and also enable it to have a stronger impact upon psychology and the
      scientific community.

PMID- 22477637
TI  - Verbal understanding: Integrating the conceptual analyses of Skinner, Ryle, and
      Wittgenstein.
AB  - Gilbert Ryle's (1949) and Ludwig Wittgenstein's (1953; 1958; 1974/78) conceptual
      analyses of verbal understanding are presented. For Ryle, the term understanding
      signifies simultaneously an acquired disposition and a behavioral episode. For
      Wittgenstein, it signifies simultaneously a skill and a criterial behavior. Both
      argued that episodes of understanding comprise heterogenious classes of
      behaviors, and that each member of such a class is neither a necessary nor a
      sufficient condition of understanding. Next, an approach integrating the analyses
      of Ryle and Wittgenstein with that of Skinner is presented. Lastly, it is argued
      that this integrated analysis adequately counters Parrott's (1984) argument that
      understanding, for Skinner, is potential behavior and not an event.

PMID- 22477638
TI  - Defining terms in behavior analysis: Reinforcer and discriminative stimulus.
AB  - Many definitions of reinforcer and discriminative stimulus found in behavioral
      texts include a requirement of temporal proximity between stimulus and response.
      However, this requirement is not consistently adopted. We present additional
      evidence from a questionnaire that was sent to members of the editorial boards of
      several behavioral journals showing that there is not universal agreement
      concerning the temporal parameters accepted in the definitions of reinforcer and
      discriminative stimulus. We suggest that the disagreement over the definitions of
      these essential terms ought to be at least addressed if not resolved. Because the
      discrepancy usually occurs when the behavior of verbal humans is at issue, we
      urge behavior analysts to be conservative when extending the terms reinforcer and
      discriminative stimulus from the behavior of nonhumans in the laboratory to human
      behavior where the effects of many stimuli may depend in part on sophisticated
      verbal repertoires.

PMID- 22477639
TI  - Racial comparison of therapeutic support, service use, and satisfaction among
      male outpatients with severe mental illness.
AB  - This study examined racial differences among male outpatients with severe mental
      illness on therapeutic support, mental health service utilization, and service
      satisfaction. A total of 530 participants (289 white, 179 black, and 62 of
      another race) across three large mental health centers (two state funded and one
      federally funded) in Connecticut were examined cross-sectionally. No racial
      differences were found in therapeutic support, and there were essentially no
      racial differences in service satisfaction. Black clients reported greater use of
      substance abuse inpatient services than White clients and clients of other racial
      minorities reported greater use of mental health inpatient services than White
      clients, but differences were small. These findings suggest there are few racial
      differences in the reported quality of mental health care and service utilization
      among male outpatients with severe mental illness. More research is needed on
      where and under what circumstances health disparities exist.

PMID- 22477640
TI  - [Fractionated inpatient rehabilitation of diabetes: results from a randomized
      controlled trial on rehabilitation aftercare].
AB  - BACKGROUND: Treating diabetes mellitus type 2 (DMT2) essentially involves long
      term changes of health behaviour, especially diet and physical activity habits.
      Medical rehabilitation tries to support these changes by patient education and
      practical instructions. While short-term successes are frequently obtained, the
      main challenge lies in maintaining these results in the longer run. This study
      examines whether a fractionated inpatient rehabilitation programme of 3 weeks
      duration in combination with an additional week of inpatient rehabilitation after
      6 months and a subsequent aftercare telephone service facilitates positive long
      term effects for patients with DMT2. METHOD: A prospective randomized controlled
      trial was conducted with 411 patients with DMT2 in order to compare the
      fractionated inpatient rehabilitation programme with aftercare to a 3-weeks
      standard rehabilitation programme without aftercare. The analysis included
      physiological (cardiovascular risk, HbA1c, BMI) and psychosocial (diabetes
      specific coping, quality of life) parameters at baseline (beginning of the
      programme) and 1 year later. RESULTS: After 12 months, no significant differences
      between the groups were found in the physiological parameters. At the same time,
      however, the aftercare group showed larger benefits in almost every psychosocial
      dimension (coping, quality of life, subjective health). Coping and quality of
      life had even improved when compared to baseline. In contrast, these parameters
      had decreased further in the standard-care control group when compared to
      baseline. CONCLUSION: The intensive aftercare was successful in the long-term
      improvement of the patients' psychological well-being. Also, the high rate of
      participation in fractionated inpatient rehabilitation suggests both the
      acceptance of and the need for aftercare. However, positive long-term changes of
      physiological parameters probably will require more specific interventions or
      individual case management. The effectiveness of fractionated inpatient
      rehabilitation may be limited by the adverse social, psychological and financial
      situation of the patients.

PMID- 22477641
TI  - Prognostic value of cardiovascular CT: is coronary artery calcium screening
      enough? The added value of CCTA.
AB  - Coronary artery disease (CAD) is the primary cause of death in adults in the
      United States. Only 50% of patients who present with a myocardial infarction have
      a prior history of CAD. Non-invasive cardiac imaging tests have been developed to
      diagnose CAD. Current guidelines and systematic reviews have tried to determine
      the prognostic value of the coronary artery calcium (CAC) scoring and the
      coronary computed tomography angiography (CCTA) for major adverse cardiovascular
      events. Several studies support the roles of CCTA and CAC scoring for the
      diagnosis of CAD in asymptomatic patients. Further studies are needed to confirm
      the superior role of CCTA over CAC scoring in symptomatic patients.

PMID- 22477642
TI  - Non-FDG imaging of atherosclerosis: will imaging of MMPs assess plaque
      vulnerability?
AB  - Acute ruptures of atherosclerotic plaques with subsequent occlusion account for
      the vast majority of clinical events such as myocardial infarction or stroke. New
      imaging approaches focusing on the visualization of inflammation in the vessel
      wall could emerge as tools for individualized risk assessment and prevention of
      events. To this end, PET employing (18)F-fluorodeoxyglucose (FDG) has recently
      been introduced for the first clinical trials. Although this approach nicely
      visualizes plaques inflammation questions remain with respect to if and how this
      inflammatory signal can be employed for predicting individual plaque rupture.
      Molecular imaging of proteases such as matrix-metalloproteinases (MMPs) involved
      in several steps in plaque progression driving plaques into vulnerable, rupture
      prone states seems a promising alternative approach. This review introduces and
      discusses the vulnerable plaque concept, animal models with human-like plaque
      ruptures and the potential of a FDG versus a non-FDG MMP-targeted strategy to
      image rupture-prone plaques.

PMID- 22477643
TI  - Association between BDNF Val66Met polymorphism and cognitive performance in
      antipsychotic-naive patients with schizophrenia.
AB  - Cognitive impairment is one of the core symptoms in schizophrenia, which reflects
      the neurodevelopmental deficits in the etiology of this disease. Brain-derived
      neurotrophic factor (BDNF) plays an important role in various neurodevelopmental
      processes. Growing evidence has shown that BDNF may be involved in the etiology
      of schizophrenia. The aim of this study was to examine the association of the
      BDNF Val66Met polymorphism with cognition in patients with schizophrenia. Various
      neuropsychological tests including the Wechsler Adult Intelligence Scale-Revised,
      the Wechsler Memory Scale-Revised, and the Wisconsin Card Sorting Test (WCST)
      were employed in a sample of 112 antipsychotic-naive patients with schizophrenia
      and 63 healthy controls. We examined the Val66Met polymorphism in the 112
      patients and 394 controls. Among the patients, cognition was compared between Met
      allele carriers and non-Met allele carriers. A wide range of cognitive deficits
      were demonstrated in the schizophrenic patients, compared with the controls (Ps <
      0.01). No significant differences of genotype or allele distribution were
      identified between patients and controls. The patients with Met allele showed
      more percent WCST perseverative errors than those without Met allele (P = 0.007).
      After stratification based on gender, an association between the Met allele and a
      higher percentage of perseverative errors was found in male patients (P = 0.014),
      but not in females (P = 0.09). Cognitive performance is broadly impaired in
      schizophrenic patients. The BDNF Val66Met polymorphism may be involved in the
      impaired executive function. This effect may have gender-specific
      characteristics.

PMID- 22477644
TI  - Compensatory recovery of blood glucose levels in KKA(y) mice fed a high-fat diet:
      insulin-sparing effects of PACAP overexpression in beta cells.
AB  - Inadequate compensatory insulin secretion is observed during the development of
      type 2 diabetes and deteriorates over time in a manner that is difficult to
      reverse. Here, we found that plasma glucose levels in genetically diabetic KKA(y)
      mice fed a high-fat diet were markedly increased in young mice. However, the
      levels started to decrease at 22 weeks of age and returned to normal levels at
      around 40 weeks of age. These changes were accompanied by a marked increase in
      insulin levels from week 25 onwards. Decreased energy intake and suppressed fat
      pad accumulation were observed at 44-45 weeks of age compared with those at 19-22
      weeks of age. beta cell-specific overexpression of pituitary adenylate cyclase
      activating polypeptide (PACAP), an insulinotropic neuropeptide, decreased the
      insulin levels required to compensate for hyperglycemia. Glucose disposal was
      significantly enhanced despite impaired insulin sensitivity in 41-44-week-old
      A(y) mice without or with PACAP overexpression. In conclusion, the present
      results provide further evidence that PACAP is involved in the regulation of
      hyperinsulinemia and islet hyperplasia in type 2 diabetes. Our results also
      indicate that A(y) mice fed a high-fat diet constitute an animal model suitable
      to study compensatory islet hyperplasia.

PMID- 22477645
TI  - Mitigation of obesity-promoted diseases by Nigella sativa and thymoquinone.
AB  - Obesity is closely associated with increased incidence of cardiovascular
      diseases, cancer, insulin resistance, and immune dysfunction, and thus obesity
      mitigation strategies should take into account these secondary pathologies in
      addition to promoting weight loss. Recent studies indicate that black cumin
      (Nigella sativa) has cardio-protective, anti-cancer, anti-diabetic, antioxidant,
      and immune-modulatory properties. While black cumin and/or its major bioactive
      constituent, thymoquinone have demonstrated bioactivity in a variety of disease
      models, the mechanisms of action are largely unknown. Given the growing interest
      in and the use of functional foods and nutraceuticals, as well as the increase in
      obesity and chronic diseases worldwide, further research into the
      therapeutic/preventive effects of black cumin may be beneficial.

PMID- 22477646
TI  - Causes of failure in removing calcium in microcalcification-only lesions using 11
      gauge stereotactic vacuum-assisted breast biopsy.
AB  - PURPOSE: The aim of this study was to determine the causes and rate of failure in
      removing calcification in microcalcification-only lesions using 11-gauge
      stereotactic vacuum-assisted breast biopsy. MATERIALS AND METHODS: In total, 1365
      microcalcification-only lesions were included in this study. The breast biopsy
      database was reviewed retrospectively. The biopsies were divided into two groups
      based on whether the specimen X-ray showed calcium within the cores. Breast
      composition, lesion size, calcification distribution, density on mammography, and
      the number of specimens were compared between the two groups. RESULTS: In 11
      (0.8%) biopsies, no calcium in the specimen radiography could be identified. Re
      biopsy was performed in five cases. The initial biopsy result was unchanged at
      the second biopsy in three cases containing calcium, while in the other two
      cases, a benign biopsy result was upgraded to atypical ductal hyperplasia and
      ductal carcinoma in situ, respectively. In six cases, the biopsy was not repeated
      despite the absence of calcium in the specimen X-ray. In three of these cases,
      calcifications were reported histopathologically and deemed to be too small to be
      identified on specimen X-ray. In two of six patients, sufficient information was
      found in the cores without microcalcification to indicate the need for surgery.
      One patient refused re-biopsy. A statistically significant higher failure rate
      was observed in low-density calcification compared with intermediate or high
      density calcification on mammography. CONCLUSION: The failure to retrieve
      microcalcification is uncommon when an 11-gauge vacuum-assisted breast biopsy is
      used. Low-density calcifications have a higher rate of failure. In cases in which
      no calcium is observed in specimen radiography, repeated biopsy is recommended.

PMID- 22477647
TI  - Percutaneous intervention strategies for the management of dysfunctioning biliary
      plastic endoprostheses in patients with malignant biliary obstruction.
AB  - PURPOSE: To present our clinical experience and to suggest different strategies
      in the management of dysfunctioning plastic biliary stents in patients with
      malignant biliary obstruction. MATERIALS AND METHODS: Twenty females and 23 males
      with a mean age of 64.8 years (range, 30-89 years) with malignant obstructive
      jaundice were referred to the interventional radiology department due to
      previously inserted dysfunctioning plastic endoprostheses. Pancreatic carcinoma
      (n=12), duodenal carcinoma (n=5), cholangiocarcinoma (n=16), gallbladder cancer
      (n=4), and metastatic disease (n=6) had been previously stented endoscopically.
      Nine of the patients had two plastic endoprostheses in the biliary tree. Forty
      nine endoprostheses were straight polyethylene stents, and three were double-J
      type plastic stents (52 endoprostheses in total). RESULTS: Forty-nine of the
      dysfunctioning plastic stents were cleared from the biliary tree. Of these, 31
      were dislodged into the bowel with the help of a balloon catheter. Threading with
      an over-the-wire diagnostic and percutaneous biliary drainage catheter was
      performed in 12 of the plastic stents. Six dysfunctioning endoprostheses were
      removed by transhepatic access. Three plastic endoprostheses could not be removed
      or dislodged. No complication occurred due to intervention. The mean follow-up
      time was nine months (range, 1-19 months). All of the patients were evaluated in
      the first month, and then at three-month intervals. Percutaneous metallic
      stenting was performed on 29 patients. CONCLUSION: Percutaneous intervention
      should be considered as an alternative treatment when a need for eliminating the
      dysfunctioning plastic stent arises. Both removal of the dysfunctioning stent and
      dislodgement into the bowel are safe and efficient strategies in the management
      of malignant biliary obstructions.

PMID- 22477648
TI  - Cardiovascular risk management of hypertension and hypercholesterolaemia in the
      Netherlands: from unifactorial to multifactorial approach.
AB  - About 30 years ago, the first Dutch unifactorial guidelines on hypertension and
      hypercholesterolaemia were developed. These guidelines have been revised several
      times, often after publication of landmark studies on new generations of drugs.
      In 1978, cut-off points for pharmacological treatment of hypertension were based
      on diastolic blood pressure values >=115 mmHg, and in 2000 they were lowered to
      >100 mmHg. From 1997 onwards, cut-off points for systolic blood pressure values
      >180 mmHg were introduced, which became leading. In 1987, cut-offs for
      hypercholesterolaemia of >=8 mmol/l were set and from 2006 pharmacological
      treatment was based on a total/HDL cholesterol ratio >8. Around 2000, treatment
      decisions for hypertension and/or hypercholesterolaemia were no longer based on
      high levels of individual risk factors, but on a multifactorial approach based on
      total risk of cardiovascular diseases (CVD), determined by a risk function. In
      the 2006 multidisciplinary guideline on cardiovascular risk management, the
      Framingham risk tables were replaced by European SCORE risk charts. A cut-off
      point of 10% CVD mortality was set in the Netherlands. In 2011, this cut-off
      point changed to 20% fatal plus nonfatal CVD risk. Nowadays, 'the lower the risk
      factors, the lower the absolute risk' is the leading paradigm in CVD prevention.

PMID- 22477650
TI  - Barbarians at the gate.

PMID- 22477649
TI  - Critical hand ischaemia after transradial cardiac catheterisation: an uncommon
      complication of a common procedure.
AB  - We describe a case of critical hand ischaemia after transradial cardiac
      catheterisation. The patient presented with hand ischaemia 5 days after
      transradial coronary angiography. Urgent angiography demonstrated radial artery
      occlusion with embolisation to the palmar arch and digital arteries. The
      ischaemia was refractory to an extensive thrombolytic regimen, and subsequently,
      the patient was referred to the vascular surgeon for urgent thrombectomy and
      patch angioplasty. The patient recovered slowly and no amputation was necessary,
      but complaints of right hand numbness and paresthesia of all digits remained.

PMID- 22477651
TI  - Erratum to: Wasting in chronic kidney disease.

PMID- 22477653
TI  - Repair and rehabilitation concept of a five-day-old radius fracture in a foal.

PMID- 22477652
TI  - [The influence of colostral antibodies on the postvaccination humoral immune
      response in neonatal calves].
AB  - The aim of this study was to evaluate the efficiency of vaccination of young
      calves and to see whether maternal antibodies may influence the immunological
      response in calves. For this project 20 matched-pairs of cows and their offspring
      were selected. Of each pair, one cow received a placebo 8 and 4 weeks before term
      (group A) and the other was vaccinated against Feline Leucose Virus, FeLV, with
      Leucogen(r) (group B). All calves received colostrum from their respective mother
      shortly after birth and all calves were vaccinated with Leucogen(r) 10 days after
      birth. Blood samples from the cows and calves were taken during the whole study
      period (till four weeks after calf vaccination). An ELISA test was done in the
      lab to define the FeLV antibody concentration. 30 % of the vaccinated cows showed
      a seroconversion, 13 out of 20 vaccinated cows passed the antibodies onto their
      calves. 11 calves of group B did not convert in comparation of only 4 of group A.
      All seroconverted calves had low antibody concentration before their vaccination.
      Calves of group B with a low passive antibody level at the beginning showed a
      higher seroconversion as compared to calves with higher antibody concentrations
      of the same group. Two thirds of the calves without maternal antibodies reacted
      adequately to the vaccination. Therefore, an early vaccination of calves can be
      recommended.

PMID- 22477654
TI  - New World camelids and Bovine Virus Diarrhea Virus (BVDV) infection in
      Switzerland.

PMID- 22477655
TI  - [First time detection of lung worms in free range swine in Switzerland].

PMID- 22477660
TI  - [Diagnosis and treatment of food allergies in preschool children].
AB  - The prevalence of food allergies in preschool children has increased in the last
      few decades. Depending on the triggering allergen, children may outgrow many
      hypersensitivity reactions to food proteins by the age of 3 - 5 years. Despite
      improved diagnosis and knowledge, food allergies are still restricting the
      quality of life in affected subjects and their families. There is a wide spectrum
      of clinical manifestation from mild cutaneous symptoms to life-threatening
      anaphylactic reaction. Food proteins are the most frequent cause of anaphylactic
      reactions in childhood and adolescence. The task of primary care physicians
      includes identification of at-risk patients, early diagnosis and advice to family
      members concerning preventive measures and emergency treatment (e. g. adrenaline)
      in case of accidental ingestion of the culprit food. There is still no causal
      treatment of food allergy available. Therefore, strict avoidance of the causative
      food remains the most important measure to date.

PMID- 22477661
TI  - [Food allergy from school age to adulthood].
AB  - In young children food allergy is mainly acquired over the gastrointestinal tract
      and directed to egg and milk. Patients at school age or adult patients, however,
      often acquire a food allergy over a primary sensitisation to inhalant allergens,
      in Switzerland primarily over birch pollen. This type of food allergy is directed
      to plant foods. Apple and hazelnut are the most prevalent allergenic foods in
      this age group. A birch pollen related food allergy is often accompanied by mild
      allergic symptoms such as the oral contact urticaria. The relevant allergens are
      labile to heat and are often tolerated in heat processed form. Severe up to
      anaphylactic symptoms, however, have been reported in birch pollen related soy
      allergy. Physical exercise, intake of alcohol, NSAIDs, betablocking agents or
      eventually antacids may aggravate the severity of a food allergic reaction.

PMID- 22477662
TI  - [Diagnostic and therapeutic procedure for two popular but quite distinct adverse
      reactions to food - fructose malabsorption and histamine intolerance].
AB  - Claiming to suffer from adverse food reactions is popular. In contrast to the
      classical food allergy, there are some pathomechanisms which are evidently dose
      dependent. Thus the procedure in diagnosis and therapy must undoubtedly differ
      from the practice when food allergy is suspected or proven. Nevertheless many
      patients suffering from dose-dependent adverse reactions to food are given strict
      elimination diets, which is neither necessary nor helpful and decreases their
      quality of life broadly. This holds especially true for fructose malabsorption
      and histamine intolerance. For the latter, the term adverse reaction to ingested
      histamine is preferred, because histamine intolerance implies that symptoms are
      caused entirely by an enzyme defect. Why this is not very likely to be the only
      reason is discussed in this article. Both adverse reactions require an individual
      approach especially with regard to nutrition therapy. Therefore the task of
      diagnosis should be to establish an individual profile of tolerated and not
      tolerated foods taking into account that tolerance can greatly vary by meal
      composition, frequency and individual triggering factors. In view of this,
      therapeutic recommendations should not be based on the absolute quantities of the
      eliciting substance to be eliminated but on a feasible transfer into daily life.
      Thereby food restriction can be minimized and a high quality of life will be
      maintained.

PMID- 22477663
TI  - [Pollen allergy and immunotherapy].
AB  - Pollinosis affects up to 25 % of the Swiss-population and increased substantially
      during the last century. Main causative pollens are birch and related pollens,
      ash pollen and grass pollen and to a lesser extent also mugwort. Diagnosis of
      Pollinosis is based on anamnesis, skin tests and determination of specific IgE in
      the serum. Treatment includes allergen avoidance, pharmacotherapy and allergen
      specific immunotherapy (SIT). A proper patient and allergen extract selection, an
      ideally adapted application regimen and good patient-guidance as well as good
      compliance and treatment adherence are decisive for the success of the SIT. SCIT
      is the regimen of choice with well demonstrated efficacy, safety and long term
      effect. Nowadays SLIT is an additional complementary approach that mainly for
      grass pollen also offers good efficacy with good safety. Under such conditions
      immunotherapy leads to a benefit in more than 80 % of pollinosis-patients.
      Component-resolved diagnosis is a very useful and important step in more specific
      diagnosis. Several approaches studying changed application regimens and using
      molecular technologies to improve the efficacy of SIT are undergoing and will
      possibly substantially improve the efficacy, safety and acceptance of SIT.

PMID- 22477664
TI  - [House dust mite allergy].
AB  - House dust mites can be found all over the world where human beings live
      independent from the climate. Proteins from the gastrointestinal tract- almost
      all known as enzymes - are the allergens which induce chronic allergic diseases.
      The inhalation of small amounts of allergens on a regular base all night leads to
      a slow beginning of the disease with chronically stuffed nose and an exercise
      induced asthma which later on persists. House dust mites grow well in a humid
      climate - this can be in well isolated dwellings or in the tropical climate - and
      nourish from human skin dander. Scales are found in mattresses, upholstered
      furniture and carpets. The clinical picture with slowly aggravating complaints
      leads quite often to a delayed diagnosis, which is accidently done on the
      occasion of a wider spectrum of allergy skin testing. The beginning of a medical
      therapy with topical steroids as nasal spray or inhalation leads to a fast relief
      of the complaints. Although discussed in extensive controversies in the
      literature - at least in Switzerland with the cold winter and dry climate - the
      recommendation of house dust mite avoidance measures is given to patients with
      good clinical results. The frequent ventilation of the dwelling with cold air in
      winter time cause a lower indoor humidity. Covering encasings on mattresses,
      pillow, and duvets reduces the possibility of chronic contact with mite allergens
      as well as the weekly changing the bed linen. Another option of therapy is the
      specific immunotherapy with extracts of house dust mites showing good results in
      children and adults. Using recombinant allergens will show a better quality in
      diagnostic as well as in therapeutic specific immunotherapy.

PMID- 22477665
TI  - [Allergies to animals and fungi].
AB  - Allergies to animals are behind the house-dust mite allergy the most frequent
      cause for indoor allergic respiratory symptoms. In case of persistent allergen
      exposure symptoms like rhinitis, itch of the skin or asthma are usually not
      perceived intensively and, thus, can not assigned to an animal or an animal
      source. In many cases animal allergies are based on a perennial allergen
      exposure. Although most likely all animals may be the cause of a respiratory
      allergy, cats, dogs, and horses are the most frequent elicitors. The diagnosis of
      an allergy to an animal needs to be set with due care, since it often causes
      emotional reactions, diverse conflicts, but also lack of understanding. Rarer are
      allergies to fungi even though fungi as allergen sources since decades belong to
      the differential diagnosis in respiratory allergies particularly in case of late
      summer asthma. Fungi are ubiquitous and present indoors as well as outdoors.
      Unfortunately the field of fungal allergy is not well explored and diagnostic
      possibilities are limited. The most promising therapy in both allergy to animals
      and fungi would be complete avoiding of contact with the respective allergen
      source. Indeed many preventive recommendations are given; however, realization is
      often not successful. In selected cases specific immunotherapy for both animal
      and fungal allergies is a potential therapeutic option.

PMID- 22477666
TI  - [Occupational rhinitis and asthma].
AB  - Allergic rhinoconjunctivits and asthma are frequent diseases. About one in ten
      asthma cases is caused by an occupational hazard, either by an allergic or a non
      immunologic mechanism. Primary or secondary preventive measures should be able to
      prevent these cases. Often, occupational rhinitis precedes the development of
      occupational asthma. Important causative agents are flours, plant and enzyme
      powders, laboratory animals, latex, isocyanates and hardeners, epoxy resins,
      acrylates, formaldehyde and welding fumes. Early diagnosis and the installation
      of protective measures are decisive for the prognosis of occupational respiratory
      disease.

PMID- 22477667
TI  - Self-perceived competence among medical residents in skills needed to care for
      patients with advanced dementia versus metastatic cancer.
AB  - To examine medical residents' perceived competence in caring for patients with
      dementia we conducted an online survey of all 120 second, third and fourth-year
      residents in Internal Medicine, Medicine/Pediatrics, and Family Medicine at
      University of Michigan. A structured survey elicited residents' training,
      experience, confidence, and perceived career needs for skills in estimating
      prognosis, symptom management, and communication in caring for patients with
      dementia, compared to patients with metastatic cancer. Among the 61 (51 %)
      respondents, a majority report lower confidence in assessing prognosis and
      eliciting treatment wishes in patients with dementia (vs. metastatic cancer), and
      in performing skills integral to the care of patients with dementia, including
      the ability to assess caregiver needs, decisional capacity, advise on place of
      care, and manage agitation, despite viewing these skills as important to their
      future careers. These findings support the need for enhanced education on optimal
      care of patients with advanced dementia.

PMID- 22477668
TI  - Severity of outcomes associated to types of HIV coinfection with TB and malaria
      in a setting where the three pandemics overlap.
AB  - The objectives of this study is to (1) characterize profiles of HIV coinfection
      with TB and malaria; (2) estimate the severity of outcome associated with each
      type of coinfection; (3) identify most severe coinfection type, and populations
      most affected. Data on 1,302 HIV/AIDS patients were collected from hospital
      record books for 2007 and 2008. Distribution patterns of types of HIV coinfection
      with TB and malaria were assessed among low and high SES (socioeconomic status)
      inpatients. Case fatality rate for each type of coinfection was estimated as the
      ratio of number of deaths associated with a specific type of coinfection over the
      number of cases, times 100. Case fatality rates were compared among coinfection
      types and between low and high SES inpatients. Four types of coinfections were
      identified: single-HIV, HIV-TB, HIV-malaria and HIV-TB-malaria. Single-HIV
      infection was the most prevalent, and predominant among high SES inpatients; HIV
      TB was the second most prevalent, and predominant among low SES inpatients; HIV
      malaria and HIV-TB-malaria coinfections were the least prevalent, they were
      relatively comparable between both SES groups. HIV-TB coinfection was the
      deadliest type of coinfection, followed by HIV-TB-malaria and HIV-malaria. Single
      HIV infection was the least deadly of the four conditions. Aside from HIV
      malaria, the proportion of fatalities associated with each coinfection type was
      higher among low SES inpatients when compared with high SES inpatients. HIV/AIDS
      treatment and care programs in communities with limited resources and high
      prevalence of malaria and TB should give priority attention to low socioeconomic
      status patients coinfected with TB to prevent unnecessary deaths among those
      living with HIV.

PMID- 22477669
TI  - Effects of hygiene and sanitation interventions on reducing diarrhoea prevalence
      among children in resource constrained communities: case study of Turkana
      District, Kenya.
AB  - Worldwide, lack of access to safe drinking water together with inadequate
      sanitation and hygiene is an overwhelming contributor to approximately 4 billion
      cases of illness annually. This study was set out to understand the effects of
      hygiene and sanitation interventions on targeted health outcomes including
      diarrhoeal prevalence in children's of Turkana District, Kenya. The interventions
      undertaken included capacity building and empowerment approach to trigger
      communities to demand hygiene and sanitation facilities. Three hundred mothers
      were randomly sampled in a baseline survey carried out in 2007 and in a post
      intervention survey carried out in 2008 (a repeat cross-sectional study design).
      Specimens were collected for microbiological tests of key diarrhoea related
      pathogens. Overall, Faecal coliform counts per 100 ml sample had significant
      variations between 2007 and 2008; in Kakuma, reduced from 88 to 30.2 colony units
      (P = 0.005), Lodwar Central where the number reduced from 91 to 17.3 units (P =
      0.003), and in Lokichogio Division, the number reduced from 63.8 to 23.6 units (P
      = 0.006). From the 230 stool samples examined, the proportion of children from
      whom infectious pathogens of Proteus spp. was isolated reduced from 16 to 7 %
      while Escherichia coli reduced from 54 to 41 %. Overall, prevalence of diarrhoea
      related microbes in children aged <5 years reduced from 91.3 % in 2007 to 78.3 %
      after intervention (2008). It is notable that sanitation and hygiene promotion
      leads to significant reduction of diarrhoea prevalence in children aged <5 years.
      Its application should therefore be up-scaled in resource constrained areas.

PMID- 22477670
TI  - Characteristics of US counties with no mammography capacity.
AB  - Access to screening mammography may be limited by the availability of facilities
      and machines, and nationwide mammography capacity has been declining. We assessed
      nationwide capacity at state and county levels from 2003 to 2009, the most recent
      year for which complete data were available. Using mammography facility
      certification and inspection data from the Food and Drug Administration, we
      geocoded all mammography facilities in the United States and determined the total
      number of fully accredited mammography machines in each US County. We categorized
      mammography capacity as counties with zero capacity (i.e., 0 machines) or
      counties with capacity (i.e.,>=1 machines), and then compared those two
      categories by sociodemographic, health care, and geographic characteristics. We
      found that mammography capacity was not distributed equally across counties
      within states and that more than 27 % of counties had zero capacity. Although the
      number of mammography facilities and machines decreased slightly from 2003 to
      2009, the percentage of counties with zero capacity changed little. In adjusted
      analyses, having zero mammography capacity was most strongly associated with low
      population density (OR = 11.0; 95 % CI 7.7-15.9), low primary care physician
      density (OR = 8.9; 95 % CI 6.8-11.7), and a low percentage of insured residents
      (OR = 3.3; 95 % CI 2.5-4.3) when compared with counties having at least one
      mammography machine. Mammography capacity has been and remains a concern for a
      portion of the US population--a population that is mostly but not entirely rural.

PMID- 22477672
TI  - Editor's Page.

PMID- 22477671
TI  - Improving health promotion to American Indians in the midwest United States:
      preferred sources of health information and its use for the medical encounter.
AB  - American Indians and Alaska Natives suffer significant health disparities for
      many infectious and chronic diseases as compared to the general population.
      Providing accurate and culturally tailored health information to underserved
      groups has been shown to influence health behaviors and health outcomes. Little
      prior research has explored American Indians health information use and
      preferences. National representative sample surveys such as the Health
      Information National Trends Survey provide some data on minority groups but are
      underpowered to provide useful information on American Indians. The present study
      analyzes data from a survey of over 900 American Indians from the Midwest United
      States and explores their sources of health information, their preferences for
      information presentation, and their use of health information prior to and during
      medical encounters. We conclude that campaigns targeting Natives should be
      narrowly focused and be community driven or employing community resources.
      American Indians use a diversity of media sources to obtain health information,
      with the Internet being underutilized compared to the general population.
      Partnership with Indian Health Service providers and pharmacists, as well as
      traditional healers, in the development and dissemination of new health
      information for Natives may provide the "expert" tone needed to promote health
      improvements in American Indians.

PMID- 22477673
TI  - Clinical application of functional analysis methodology.
AB  - Functional analysis (FA) methodology is a well-established standard for
      assessment in applied behavior analysis research. Although used less commonly in
      clinical (nonresearch) application, the basic components of an FA can be adapted
      easily in many situations to facilitate the treatment of problem behavior. This
      article describes practical aspects of FA methodology and suggests ways that it
      can be incorporated into routine clinical work.

PMID- 22477674
TI  - Functional analysis and treatment of chronic hair pulling in a child with cri du
      chat syndrome: effects on co-occurring thumb sucking.
AB  - The relation between hair pulling and thumb sucking in a child with Cri du Chat
      syndrome was evaluated during the assessment and treatment of hair pulling. A
      functional analysis suggested that both behaviors were maintained by automatic
      reinforcement and possibly by attention. Treatment combining differential
      reinforcement (praise), response interruption, and access to toys decreased hair
      pulling. A corresponding decrease in thumb sucking was observed even though it
      was not directly treated. After an initial evaluation in a controlled setting,
      the treatment was extended to the participant's classroom setting. A 1-year
      follow up revealed that hair pulling, but not thumb sucking, remained at near
      zero frequency. Clinical and research-to-practice implications are discussed.

PMID- 22477675
TI  - Functional communication training: a review and practical guide.
AB  - Functional communication training (FCT) is one of the most common and effective
      interventions for severe behavior problems. Since the initial description of FCT
      by Carr and Durand (1985), various aspects of the FCT treatment process have been
      evaluated, and from this research, best practices have emerged. This manuscript
      provides a review of these practices as they arise during the development of
      effective FCT interventions.

PMID- 22477676
TI  - Simulation training of community job skills for adults with autism: a further
      analysis.
AB  - We evaluated the benefits of training work skills in a simulated situation to
      adults with autism by examining their performance at a job site. In the first
      study, simulation training on new work tasks included the same materials and job
      coach from the job setting (i.e., a common stimuli approach to promote
      generalization). In the second study, each participant received training on new
      work tasks using materials that were different from those in the job setting. In
      both studies, simulation training was accompanied by improvement in each
      participant's subsequent job performance. Results are discussed regarding the
      importance of using research-based procedures in supported work versus practices
      that are currently popular but not necessarily based on research. Working
      guidelines are offered for using simulation training to promote more success in
      supported work among adults with disabilities on the severe end of the autism
      spectrum.

PMID- 22477677
TI  - Teaching safety skills to children: prevention of firearm injury as an exemplar
      of best practice in assessment, training, and generalization of safety skills.
AB  - The focus of this paper is on teaching safety skills to children with an emphasis
      on recent research on behavioral skills training for the prevention of firearm
      injury. Following a discussion of safety skills and methods for assessing these
      skills, the paper reviews recent research on behavioral skills training and in
      situ training for teaching safety skills to prevent firearm injury. Strategies
      for promoting generalization and increasing the efficiency of training are then
      discussed, along with a summary of conclusions that can be drawn from the
      research and guidelines for best practices in teaching safety skills to children.

PMID- 22477678
TI  - A Comparison of Most-to-Least and Least-to-Most Prompting on the Acquisition of
      Solitary Play Skills.
AB  - Two studies are presented in which common prompting procedures were evaluated
      while teaching children with autism to build Lego((r)) play structures. In the
      first study, most-to-least (MTL) and least-to-most (LTM) prompting were compared.
      All participants learned to build the play structures when the teacher used MTL,
      which was associated with fewer errors than LTM. Nonetheless, three participants
      learned more quickly with LTM. This finding suggests that MTL may prevent errors,
      but it sometimes slows learning. The second study compared LTM to MTL without and
      with a delay (MTLD). MTLD provided an opportunity for the child to independently
      initiate responding but still minimized the likelihood of errors. Results showed
      that acquisition was nearly as rapid when the teacher used MTLD as LTM but it
      produced fewer errors than LTM. Best practice guidelines for choosing prompting
      procedures are proposed.

PMID- 22477680
TI  - List of guest associate editors and guest reviewers.

PMID- 22477679
TI  - The behavior analyst certification board and the profession of behavior analysis.
AB  - As applied behavior analysis has matured as a field, matters regarding
      credentialing have followed. Such issues surround how to identify quality
      behavior analytic services and to ensure that they are delivered to consumers.
      The Behavior Analyst Certification Board was developed to address such concerns.
      In this paper, we discussed the current status and impact of the BACB, along with
      several challenges that are facing the profession. Suggested solutions for
      managing these challenges are provided.

PMID- 22477681
TI  - An Introduction to the Second Issue of Behavior Analysis in Practice (BAP).

PMID- 22477682
TI  - Practical implications of data reliability and treatment integrity monitoring.
AB  - Data reliability and treatment integrity have important implications for clinical
      practice because they can affect clinicians' abilities to accurately judge the
      efficacy of behavioral interventions. Reliability and integrity data also allow
      clinicians to provide feedback to caregivers and to adjust interventions as
      needed. We present reasons why reliability and integrity measures are paramount
      in clinical work, discuss events that may result in decreased reliability or
      integrity, and provide several efficient means for collecting data and
      calculating reliability and integrity measures.

PMID- 22477683
TI  - The effects of a group contingency intervention on academic engagement and
      problem behavior of at-risk students.
AB  - A successful learning environment can be characterized by actively engaged
      students displaying appropriate student behavior. We implemented a group
      contingency intervention as a novel component to a school-wide behavior
      management system to decrease the frequency of inappropriate behaviors and,
      conversely, increase the academic engagement of students in four elementary
      school classrooms. Twelve students with behavioral risks served as target
      students to monitor effects. A reversal design was implemented to evaluate
      behaviors across experimental conditions. Results indicated that the frequency of
      inappropriate behaviors decreased and academic engaged time increased for all 12
      participants. These results suggested that the group contingency was an effective
      class-wide intervention. Implications for research and practice are discussed.

PMID- 22477684
TI  - Treatment integrity of school-based behavior analytic interventions: a review of
      the research.
AB  - A growing body of evidence suggests that treatment integrity of school-based
      behavior analytic interventions is related to intervention outcomes. These
      findings are of importance to behavior analysts, educators, and other
      practitioners working in school settings, and indicate that these professionals
      should be knowledgeable in the assessment of treatment integrity. In this
      article, we describe the methods used to measure treatment integrity in research
      and summarize the findings on consultation characteristics that affect treatment
      integrity. Based on the reviewed research, recommendations are offered to
      behavior analysts and school professionals to aid in the measurement and
      maintenance of treatment integrity in school settings.

PMID- 22477685
TI  - Self-monitoring of pace to improve math fluency of high school students with
      disabilities.
AB  - This study illustrates how a behavioral self-management intervention, which
      combined tactile and visual cued self-monitoring, self-graphing, and goal
      setting, improved the math fluency of five high school students with various
      disabilities during independent math practice. The intervention helped students
      monitor, adjust, and increase the pace at which they produced answers to simple
      addition and subtraction problems during daily 3-minute sessions. Using the self
      management techniques, the students systematically increased the number and pace
      of correct responses, and concurrently, kept the number of error responses
      minimal and maintained or improved accuracy of responses. The paper includes
      recommendations for teaching students how to monitor their own academic
      performances rather than relying on teachers.

PMID- 22477686
TI  - Effects of self-graphing and goal setting on the math fact fluency of students
      with disabilities.
AB  - We evaluated the impact of goal setting and students' participation in graphing
      their own performance data on the rate of math fact calculations. Participants
      were 3 students with mild disabilities in the first and second grades; 2 of the 3
      students were also identified with Attention-Deficit/Hyperactivity Disorder
      (ADHD). They were taught to use Microsoft Excel(r) software to graph their rate
      of correct calculations when completing timed, independent practice sheets
      consisting of single-digit mathematics problems. Two students' rates of correct
      calculations nearly always met or exceeded the aim line established for their
      correct calculations. Additional interventions were required for the third
      student. Results are discussed in terms of implications and future directions for
      increasing the use of evaluation components in classrooms for students at risk
      for behavior disorders and academic failure.

PMID- 22477687
TI  - Science, skepticism, and applied behavior analysis.
AB  - Pseudoscientific claims concerning medical and psychological treatments of all
      varieties are commonplace. As behavior analysts, a sound skeptical approach to
      our science and practice is essential. The present paper offers an overview of
      science and skepticism and discusses the relationship of skepticism to behavior
      analysis, with an emphasis on the types of issues concerning behavior analysts in
      practice.

PMID- 22477688
TI  - Using behavior analysis to examine the outcomes of unproven therapies: an
      evaluation of hyperbaric oxygen therapy for children with autism.
AB  - It has become increasingly common for parents of children with autism to
      supplement behavior analytic interventions with therapies that have not yet been
      subjected to adequate scientific scrutiny. When caregivers elect to use unproven
      therapies despite advice to the contrary, practitioners should employ the methods
      of applied behavior analysis to experimentally evaluate the outcomes. Controlled
      evaluations of unproven therapies can be challenging, however, particularly when
      ongoing behavioral services are supplemented with biomedical interventions. This
      paper describes the methods and results of a behavior analytic evaluation of
      hyperbaric oxygen therapy, an unproven intervention that has been growing in
      popularity over the past several years. Three young children with autism
      participated. No benefits of the therapy were evident beyond those obtained
      through the behavioral intervention alone. Considerations for conducting this
      type of research are highlighted, along with suggestions for practitioners.

PMID- 22477689
TI  - Remediating minimal progress on teaching programs by adults with severe
      disabilities in a congregate day setting.
AB  - We evaluated a modified teaching approach for improving the performance of adults
      with severe disabilities who were making minimal progress on teaching programs in
      a congregate day setting. An approach for enhancing progress was developed for
      implementation within the ongoing routine of the adult day setting using
      resources indigenous to the setting. The teaching approach, based on early
      intensive teaching programs, involved increasing teaching trials, adding another
      consequence to the reinforcement component, and reducing distractions. Improved
      progress accompanied the approach with each of 4 participating adults. Measures
      of happiness and problem behavior showed no detrimental effect on quality of
      life. Advantages and disadvantages of the teaching approach are discussed
      regarding implications for practitioners.

PMID- 22477691
TI  - An Introduction to the Volume 2, Number 1 of Behavior Analysis in Practice (BAP).

PMID- 22477690
TI  - Treating non-retentive encopresis with rewarded scheduled toilet visits.
AB  - We evaluated the effects of rewarded scheduled toilet sits on non-retentive
      encopretic behavior of an elementary-school student receiving services for
      serious emotional disturbance. A multidisciplinary team implemented the 8-week
      intervention using a multiple baseline across settings design. The results showed
      an increase in sitting on the toilet and a decline in encopretic episodes in both
      school and home settings. These findings support the use of a behavioral
      intervention for children with significant behavioral disorders within a
      classroom setting.

PMID- 22477692
TI  - Facilitating the adoption of contingency management for the treatment of
      substance use disorders.
AB  - Contingency management (CM) is an effective treatment strategy for addressing
      many types of substance abuse disorders and associated problems. Nonetheless, CM
      protocols have not been widely embraced by community-based treatment providers.
      Exploration of the viability of CM outside of a research context remains largely
      an academic pursuit. In this paper, we outline several areas that may hinder the
      transfer of CM technology into community-based practice settings, review the
      literature that may address these barriers, and offer suggestions to researchers
      for overcoming them.

PMID- 22477693
TI  - Teaching teenagers with autism to answer cell phones and seek assistance when
      lost.
AB  - Three participants with autism were taught to answer a cell phone and to follow
      directions to seek assistance when lost in community settings. During baseline,
      none of the participants answered a cell phone or sought assistance. Following
      instruction at school and in the community, all participants learned to answer
      the cell phone and follow instructions to seek assistance from a naive adult by
      exchanging a communication card. Generalization probes were conducted in non
      training community sites and with the participants' parents. Data also were
      collected on the responses of naive community members to determine the social
      validity of the participants' assistance-seeking skills. Results are discussed in
      terms of the importance of teaching community safety skills to individuals with
      autism and the challenges of teaching these responses to individuals with severe
      communication and social deficits.

PMID- 22477694
TI  - Rapid training of a community job skill to nonvocal adults with autism: an
      extension of intensive teaching.
AB  - We evaluated an intensive program in a simulated format for rapidly teaching a
      job skill to nonvocal adults with autism. Following baseline probes with a new
      work task of assembling mailing boxes at a publishing company, 3 supported
      workers individually received repeated teaching sessions at a simulated work
      site. All workers met criterion with 1 day of simulation teaching, with
      subsequent criterion level performance upon returning to the job (1 worker
      required booster trials). Intensive teaching did not occasion problem behavior
      nor unhappiness indices. Improved work performance also occurred with two
      generalization tasks involving different materials. Implications for
      practitioners focus on improving worker performance without interfering with work
      completion that often accompanies on-the-job training. Potential applications of
      intensive programs for rapidly teaching other skills are discussed.

PMID- 22477695
TI  - Treatment of selective and inadequate food intake in children: a review and
      practical guide.
AB  - Treatment of highly selective or low overall eating by children may prevent the
      development of more complicated feeding difficulties, which can result in
      compromised health status and developmental concerns as well as the need for more
      intensive interventions. Caregiver-friendly intervention strategies that can be
      implemented with children in their community environments (e.g., in the child's
      home or school) may reduce the need for tertiary care. A small but growing number
      of studies have found that certain behavioral procedures can be effective in the
      absence of escape extinction with children who have established eating patterns
      (i.e., inadequate intake, selectivity by food type). This article reviews these
      procedural variations within the behavioral pediatric feeding literature and
      provides a practical guide for individuals who develop behavioral interventions
      for children in community settings.

PMID- 22477696
TI  - A primer on professional credentialing: introduction to invited commentaries on
      licensing behavior analysts.
AB  - Questions have arisen recently about the relative merits of certification and
      licensure for protecting practitioners of behavior analysis and consumers of
      their services. The two approaches to credentialing have short- and long-term
      implications for practitioners, consumers, and the field. To provide background
      for the invited commentaries on these issues, we describe similarities and
      differences in the two types of professional credentials.

PMID- 22477697
TI  - The case for licensure of applied behavior analysts.
AB  - The evolution of the field of applied behavior analysis to a practice-oriented
      profession has created the need to ensure that the consumers of these services
      are adequately protected. We review the limitations of the current board
      certification process and present a rationale for the establishment of licensing
      standards for applied behavior analysts on a state-by-state basis.
      Recommendations for securing the passage of a licensure bill also are discussed.

PMID- 22477698
TI  - Licensing behavior analysts: risks and alternatives.
AB  - Under certain conditions, obtaining state laws to license practitioners of
      behavior analysis might be feasible and could produce benefits for practitioners
      and consumers. Those conditions are not yet in place in most states, however, and
      pursuing licensure prematurely carries substantial risks for the entire field. We
      describe the most serious risks and the conditions that make it more or less
      likely that licensure initiatives will succeed. Finally, we recommend strategies
      for securing recognition of practitioners of behavior analysis in laws,
      regulations, and policies that can minimize risks.

PMID- 22477699
TI  - Development of a real time PCR assay for rapid detection of Vibrio
      parahaemolyticus from seafood.
AB  - A real time PCR assay for the detection of Vibrio parahaemolyticus in seafood
      samples was developed using a novel specific target and a competitive internal
      amplification control (IAC). The specificity of this assay was evaluated using
      390 bacterial strains including V. parahaemolyticus, and other strains belonging
      to Vibrio and non-Vibrio species. The real time PCR assay unambiguously
      distinguished V. parahaemolyticus with a detection sensitivity of 4.8 fg per PCR
      with purified genomic DNA or 1 CFU per reaction by counting V. parahaemolyticus
      colonies. The assays of avoiding interference demonstrated that, even in the
      presence of 2.1 MUg genomic DNA or 10(7) CFU background bacteria, V.
      parahaemolyticus could still be accurately detected. In addition, the IAC was
      used to indicate false-negative results, and lower than 94 copies of IAC per
      reaction had no influence on the detection limit. Ninety-six seafood samples were
      tested, of which 58 (60.4%) were positive, including 3 false negative results.
      Consequently, the real time PCR assay is effective for the rapid detection of V.
      parahaemotyticus contaminants in seafood.

PMID- 22477700
TI  - An examination of the OMIM database for associating mutation to a consensus
      reference sequence.
AB  - Gene mutation (e.g. substitution, insertion and deletion) and related phenotype
      information are important biomedical knowledge. Many biomedical databases (e.g.
      OMIM) incorporate such data. However, few studies have examined the quality of
      this data. In the current study, we examined the quality of protein single-point
      mutations in the OMIM and identified whether the corresponding reference
      sequences align with the mutation positions. Our results show that close to 20%
      of mutation data cannot be mapped to a single reference sequence. The failed
      mappings are caused by position conflict, site shifting (peptide, N-terminal
      methionine) and other types of data error. We propose a preliminary model to
      resolve such inconsistency in the OMIM database.

PMID- 22477701
TI  - An Introduction to the Volume 2, Number 2 of Behavior Analysis in Practice (BAP).

PMID- 22477702
TI  - A tribute to sidney w. Bijou, pioneer in behavior analysis and child development:
      key works that have transformed behavior analysis in practice.
AB  - Sidney W. Bijou's contributions to the practice of behavior analysis spanned
      nearly 7 decades, and they continue to influence what is considered "best
      practice" in our field today. By extending basic behavioral phenomena conducted
      with nonhuman animals to children in laboratory and naturalistic settings,
      Bijou's early research sparked a watershed of similar extensions. More
      importantly, Bijou's approach has led to a greater understanding of child
      development and behavior. This tribute will highlight what may be three of
      Bijou's most significant contributions to practice, namely his studies on (a)
      programmed instruction for children with developmental disabilities (Bijou,
      Birnbrauer, Kidder, & Tague, 1966), (b) children's responding under schedules of
      reinforcement and extinction (Bijou, 1957), and (c) the use of descriptive
      analysis to identify functional relations (Bijou, Peterson, & Ault, 1968).

PMID- 22477703
TI  - A preliminary analysis of the effects of coaching feedback on teacher
      implementation fidelity of first step to success.
AB  - First Step to Success (FSS) is a "manualized" intervention with documented
      effectiveness in reducing problem behaviors for young children at risk for school
      failure. This study is a preliminary analysis focusing on the role of performance
      feedback from FSS coaches on the fidelity with which teachers implemented FSS.
      Three typically developing students (2 kindergarten and 1 first grade) and their
      respective teachers served as participants. Student behavior and teacher
      implementation fidelity were assessed using a nonconcurrent multiple baseline
      design across student/teacher dyads, in which a no coaching baseline was followed
      by a performance feedback condition. The baseline phase showed modest levels of
      implementation fidelity and initial low levels of problem behavior followed by
      gradually increasing trends. A relation was demonstrated between coaching
      feedback and improved implementation fidelity. In addition, improved fidelity was
      associated with improvements in student problem behavior. Implications are drawn
      for clinical application of FSS and other "manualized" interventions.

PMID- 22477704
TI  - A tutorial on the concept of the motivating operation and its importance to
      application.
AB  - Motivating operations (MOs) exert a powerful influence over operant relations and
      hold significant implications for those working in applied settings. In this
      paper, we describe the concept of the MO and provide "real world" examples.
      Particular emphasis is given to the concept of the conditioned MO (CMO).
      Implications for intervention are discussed. It is hoped that this endeavour will
      encourage the utilization of the full conceptual system of the MO.

PMID- 22477705
TI  - Teleconsultation in school settings: linking classroom teachers and behavior
      analysts through web-based technology.
AB  - This paper describes a technically driven, collaborative approach to assessing
      the function of problem behavior using web-based technology. A case example is
      provided to illustrate the process used in this pilot project. A school team
      conducted a functional analysis with a child who demonstrated challenging
      behaviors in a preschool setting. Behavior analysts at a university setting
      provided the school team with initial workshop trainings, on-site visits, e-mail
      and phone communication, as well as live web-based feedback on functional
      analysis sessions. The school personnel implemented the functional analysis with
      high fidelity and scored the data reliably. Outcomes of the project suggest that
      there is great potential for collaboration via the use of web-based technologies
      for ongoing assessment and development of effective interventions. However, an
      empirical evaluation of this model should be conducted before wide-scale adoption
      is recommended.

PMID- 22477706
TI  - Increasing independence of adults with autism in community activities: a brief,
      embedded teaching strategy.
AB  - We evaluated a brief, embedded teaching strategy for increasing the independence
      of adults with autism in performing community activities. Initially, community
      situations were observed to identify an activity that a support staff was
      performing for an individual. The staff person was then trained to implement SWAT
      Support (say, wait and watch, act out, touch to guide) involving least-to-most
      prompting and praise to teach the individual on the spot to complete the
      activity. SWAT Support was implemented by support staff with 3 adults during
      break activities at a community job (Study 1), with 1 adult in a grocery store
      (Study 2), and with another individual in a secretary's office (Study 3). All
      applications of embedded teaching were accompanied by increased participant
      independence, which generally maintained across follow-up periods of up to 33
      weeks. Results are discussed regarding how practitioners could use the teaching
      strategy to reduce staff and caregiver completion of activities for adults with
      autism and increase active community participation.

PMID- 22477707
TI  - Behavior analysis in the era of medicalization: the state of the science and
      recommendations for practitioners.
AB  - Recent decades have witnessed an increase in biological explanations of common
      disorders such as depression and anxiety, a phenonmenon termed "medicalization"
      (Conrad, 2007). Behavior analysts may find it difficult to implement non-drug
      treatment with a populace that has become inundated with biological explanations
      and a preference for medication as the treatment of choice. Research frequently
      cited in support of medicalization includes studies of drug effectiveness, as
      well as family studies and studies of brain structure and function.
      Methodological and interpretation difficulties within those bodies of research
      are described and recommendations are made so that behavioral practitioners may
      function optimally within the culture of biological causation.

PMID- 22477708
TI  - 'Primum non nocere': A review of Taking America off Drugs: Why Behavioral Therapy
      is More Effective for Treating ADHD, OCD, Depression and Other Psychological
      Problems by Stephen Ray Flora.
AB  - Taking America off Drugs by Stephen Ray Flora provides an overview of effective
      behavioral interventions to treat a variety of mental health concerns, including
      depression and phobias. These disorders are better treated with behavioral than
      psychopharmacological interventions. Yet, the latter prevail in today's society.
      Taking America off Drugs provides the background to help us understand why, as it
      puts the treatment of behavioral disorders in the context of modern psychiatry
      and its relationship with the pharmaceutical industry. This review provides an
      overview and critical evaluation of the book, but it also extends its context by
      discussing the history of the treatment of mental illness and practices of the
      pharmaceutical-medical complex and by offering an optimistic scenario by which
      psychopharmacological agents will ultimately be replaced by interventions based
      on the principles of applied behavior analysis.

PMID- 22477709
TI  - RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and
      modulates the PTEN/PI3K/Akt signaling pathway.
AB  - Emerging evidence indicates that RhoE as novel member of the Rho GTPases family
      plays an essential role in carcinogenesis and tumor progression of human various
      tumors, but the functional significance of RhoE in human esophageal squamous cell
      carcinoma (ESCC) is still unclear. In the current study, RhoE expression in ESCC
      tissues and cells was examined, and the biological functions of RhoE in ESCC
      cells were determined. The results revealed that RhoE expression at mRNA and
      protein levels was significantly downregulated in ESCC tissues and cell lines (P
      < 0.05). RhoE expression was tightly associated with differentiation degree,
      clinical staging, and lymph node metastasis of the patients with ESCC (P < 0.05),
      but no significant correlations were found between RhoE expression and gender or
      age of the patients with ESCC (P > 0.05). Additionally, we found that
      downregulation of RhoE expression in ESCC cells promoted cell proliferation, cell
      cycle progression, as well as cell invasion in vitro, and inhibited cell
      apoptosis. Conversely, upregulation of RhoE expression in ESCC cells inhibited
      cell proliferation, arrested cell cycle at G0/G1 phase, reduced cell invasion,
      and promoted cell apoptosis. Furthermore, the downregulation of RhoE expression
      significantly reduced PTEN level and enhanced pAkt level; however, elevation of
      RhoE expression markedly increased PTEN level and decreased pAkt level. Stepwise
      investigations demonstrated that overexpression of RhoE in ESCC cells increased
      the expressions of p27 and bax proteins but decreased the expressions of cyclin
      D1 and bcl-2 proteins. These data demonstrate that RhoE may play a driving role
      in the development and progression of ESCC, and targeting the RhoE may be an
      effective and feasible approach for treatment of ESCC.

PMID- 22477710
TI  - Kallikrein-related peptidase 6 (KLK6)gene expression in intracranial tumors.
AB  - Kallikrein-related peptidases (KLKs) are emerging novel new biomarkers for
      prognosis, diagnosis and therapeutic intervention of cancer. Kallikrein-related
      peptidase 6 (KLK6) has the highest expression in normal brain among other
      tissues. Although its expression has been extensively studied in many types of
      cancer and in neurodegenerative diseases, very little is known for its expression
      in intracranial tumors. In the present study, 73 intracranial tumor samples were
      examined for KLK6 messenger ribunucleic acid (mRNA) gene expression using
      quantitative real-time polymerase chain reaction. Statistical analysis revealed
      the significant association of KLK6 expression with clinical and pathological
      parameters. Follow-up information was available for a median time of 20 months
      (range 1-59 months). KLK6 is expressed more frequently in tumors of high
      malignancy like the glioblastomas (70.6 %) and less in tumors of low malignancy
      like the meningiomas (12.5 %). KLK6 positive expression is associated with tumor
      grade (p < 0.001), malignancy status (p < 0.001), and tumor histologic type (p =
      0.001). Cox proportional hazard regression model using univariate analysis
      revealed for the first time that positive KLK6 expression is a significant factor
      for disease-free survival (DFS; p = 0.041) of patients suffering from
      intracranial tumors. Kaplan-Meier survival curves demonstrated that negative KLK6
      expression is significantly associated with longer DFS (p = 0.032). KLK6 gene
      expression may have clinical utility as a marker of unfavorable prognosis for
      intracranial tumors, and consequently, it could be used as target for therapeutic
      intervention.

PMID- 22477711
TI  - Natural withanolide withaferin A induces apoptosis in uveal melanoma cells by
      suppression of Akt and c-MET activation.
AB  - Uveal melanoma (UM) is the most common primary intraocular malignancy in adults.
      While effective therapy exists for the primary tumor, there is a lack of
      effective treatment for metastatic disease currently. Natural withanolide
      withaferin A (WA) has shown efficacy in cancers demonstrating upregulation of pro
      survival pathways. The purpose of the present study is to investigate the effect
      of WA as a potential therapeutic agent for UM in vitro as well as in vivo. UM
      cells were treated with WA and several cell-based assays, such as MTS, trypan
      blue exclusion assay, clonogenic, wound healing, cell cycle shift, annexin
      V/propidium iodide, and Western blot, were performed. In vivo experiments
      utilized the 92.1 cells in a xenograft murine model. WA inhibits cell
      proliferation of uveal melanoma cells with an IC50 of 0.90, 1.66, and 2.42 MUM
      for OMM2.3, 92.1, and MEL290 cells, respectively. Flow cytometry analysis
      demonstrates G2/M cell cycle arrest and apoptosis at 1 MUM WA in treated cells.
      WA induced apoptosis partly through the suppression of c-Met, Akt, and Raf-1
      signaling activation. In vivo studies using WA reduced tumor growth in 100% of
      animals (p = 0.015). Our observation indicates that WA is a potent drug that
      inhibits cell proliferation, shifts cell cycle arrest, and induces apoptosis in
      multiple UM cell lines in vitro. WA-mediated apoptosis in UM cells is partly
      mediated though the suppression of c-Met and Akt activation. WA significantly
      decreases UM tumor growth in vivo and justifies further evaluation of this drug
      for the treatment of metastatic uveal melanoma.

PMID- 22477713
TI  - Caecal herniation through the foramen of Winslow: a rare cause of bowel
      obstruction.
AB  - Internal herniation through the foramen of Winslow is a rare cause of abdominal
      hernia. We describe a case in which caecal herniation through the foramen of
      Winslow was diagnosed using various imaging modalities, including computed
      tomography and managed operatively through hernia identification, caecal
      reduction and foramen closure. The literature is subsequently reviewed to
      highlight previous similar episodes and identify the optimal modalities for pre
      operative diagnosis and describe the most appropriate intra-operative management.

PMID- 22477714
TI  - Similarities and differences of self-care behaviors between Korean Americans and
      Caucasian Americans with heart failure.
AB  - PURPOSE: To compare the differences of self-care behaviors between Korean
      Americans with heart failure (HF) and Caucasian Americans with HF. METHOD: Ninety
      (N = 90) participants (45 Korean Americans and 45 Caucasian Americans) were
      recruited for this study. A two-group, comparative, descriptive design using the
      Revised Heart Failure Self-Care Behavior Scale was used to assess self-care
      behaviors. RESULTS: Self-care behavior was not significantly different between
      the two groups (p > .05). However, culture-specific self-care behaviors were
      evident between two racial groups. DISCUSSION: Implementation of culturally
      congruent education programs could be useful in preventing and managing HF.
      Further studies comparing self-care behaviors should be conducted in diverse
      racial populations.

PMID- 22477712
TI  - The p53-independent induction of apoptosis in breast cancer cells in response to
      proteasome inhibitor bortezomib.
AB  - An important hallmark of cancer cells is acquired resistance toward apoptosis.
      The apoptotic pathway is the most well-defined cell death program and is
      characterized by several morphological and biochemical features. The tumor
      suppressor protein p53 is a critical regulator of apoptosis in many cell types.
      p53 stimulates a wide network of signals that act through either extrinsic or
      intrinsic pathways of apoptosis. However, a number of studies have shown that
      apoptosis can be induced in a p53-independent manner as well. In this study, we
      examined the mechanism of apoptosis in p53-null breast cancer cells in response
      to the proteasome inhibitor bortezomib. Initially, we determined the p53 status
      of 4T1 breast carcinoma and 4THMpc (a highly mestatic derivative of 4T1) cells
      and verified that both cells are p53 deficient. It was subsequently shown that
      apoptosis can be induced in both cells in a dose-dependent manner in response to
      bortezomib treatment, based on DNA fragmentation evidence. Western blot analyses
      of ubiquitin-protein conjugates additionally showed that the proteasome is
      potently inhibited by bortezomib in p53-null 4T1 and 4THMpc cells. The results
      presented in the current study also show that caspase-3 is significantly
      activated in response to the treatment with bortezomib, implying that induction
      of apoptosis in these p53-deficient cells is occurring via caspase-3. The
      additional results presented here suggest that the pro-apoptotic proteins Bad,
      Noxa, and Puma are not critical regulators of apoptosis induction in p53-null 4T1
      and 4THMpc cells. Similarly, there was no difference in the expression level of
      Mcl-1 in treated cells, suggesting that this anti-apoptotic protein is also
      uninvolved in the apoptotic response resulting from bortezomib treatment. In
      contrast, a very significant upregulation of the anti-apoptotic protein Hsp25/27
      was detected in these p53-deficient cells after treatment with bortezomib. If the
      increased expression of Hsp25/27 protein levels are muting the apoptotic effects
      of the bortezomib treatment, then the apoptosis-inducing effects of such
      proteasome inhibitors might be increased with approaches simultaneously
      inhibiting Hsp25/27 protein in p53-deficient cells.

PMID- 22477715
TI  - Cultural practices and end-of-life decision making in the neonatal intensive care
      unit in Taiwan.
AB  - The purpose of this research was to describe conditions of decision making for
      dying infants and cultural effects on the process of infant death in the neonatal
      intensive care unit. A retrospective chart review was used in this research.
      Fifty charts were reviewed; the major cause of death for the research subjects
      was complications of prematurity (52%). Eighty-two percent of the charts
      documented a do not resuscitate order, and 16% of parents allowed discontinuation
      of ventilator support when they realized the futility of continued care. In 30
      nursing records, parents and their dying infants were offered a quiet place in
      which to grieve. In 10 cases, nurses accompanied these parents and allowed them
      to express their emotions. Research findings showed great outward expression of
      religion at the time of death. Various cultural issues affected both the grieving
      process of the families and the dying process of their infants.

PMID- 22477716
TI  - Age-related differences in health beliefs regarding cervical cancer screening
      among Korean American women.
AB  - Cervical cancer screening rates among older Korean American (KA) women are much
      lower than the rates for younger KA women, even though the overall cancer
      screening rates in the population continue to have one of the lowest Papanicolaou
      (Pap) test adherence rates compared with non-Hispanic White women. Variables
      based on the Health Belief Model related to cervical cancer screening were
      compared by age group among KA women. A telephone survey was conducted with 189
      KA women living in the midwestern United States. Perceived barriers to having a
      Pap test predicted the outcome variable of having had Pap tests in the preceding
      3 years in older KA women who were 65 or older, but not in younger women who were
      between 40 and 64 years old. Having physical examinations without symptoms in the
      preceding 2 years predicted the outcome variable in both age groups. Intervention
      strategies for all KA women should focus on encouraging them to receive routine
      physical examinations. In addition, attempts should be made to reduce perception
      of barriers in older KA women to improve their cervical cancer screening
      behaviors.

PMID- 22477717
TI  - Development of scales to assess patients' perception of physicians' cultural
      competence in health care interactions.
AB  - This study describes the development of scales to measure patients' perception of
      physicians' cultural competence in health care interactions and thus contributes
      to promoting awareness of physician-patient intercultural interaction processes.
      Surveys were administrated to a total of 682 participants. Exploratory factor
      analyses were employed to assess emergent scales and subscales to develop
      reliable instruments. The first two phases were devoted to formative research and
      pilot study. The third phase was devoted to scale development, which resulted in
      a five-factor solution to measure patient perception of physicians' cultural
      competence for patient satisfaction.

PMID- 22477718
TI  - European higher health care education curriculum: development of a cultural
      framework.
AB  - This article concerns the European Curriculum in Cultural Care Project (2005
      2009), which aimed at developing a curriculum framework for the enhancement of
      cultural competence in European health care education. The project was initiated
      and supported by the Consortium of Institutes in Higher Education in Health and
      Rehabilitation, whose goal is to nurture educational development and networking
      among member institutions. The framework is the result of a collaborative
      endeavor by nine nurse educators from five different European countries. The
      production of the framework will be described in accordance with the following
      tenets: developing cultural competence is a continuing process, cultural
      competence is based on sensitivity toward others, and cultural competence is a
      process of progressive inquiry. Critique concerning the framework will be
      presented.

PMID- 22477719
TI  - Cultural self-efficacy of Canadian nursing students caring for aboriginal
      patients with diabetes.
AB  - Cultural self-efficacy refers to how capable one feels functioning in culturally
      diverse situations. The purpose of this study was to gain a better understanding
      of cultural self-efficacy among nursing students, specifically in relation to
      individuals of Aboriginal ancestry. The authors examined the extent to which
      intercultural anxiety, intercultural communication, and experience with persons
      of Aboriginal ancestry predicted two aspects of cultural self-efficacy, namely,
      knowledge and skills. In this correlational study, non-Aboriginal Canadian
      nursing students (N = 59) completed a survey assessing these variables. Overall,
      cultural self-efficacy was rated as moderate by nursing students. Regression
      analyses indicated that greater intercultural communication skills and experience
      with persons of Aboriginal ancestry were significant unique predictors of higher
      cultural knowledge self-efficacy. Greater intercultural communication and lower
      intercultural anxiety significantly predicted higher cultural skills self
      efficacy. The results provide direction to nursing programs interested in
      facilitating higher levels of cultural self-efficacy among nursing students.

PMID- 22477720
TI  - Attitudes toward and justification for wife abuse among Syrian medical and
      nursing students.
AB  - PURPOSE: To explore the perceptions of and attitudes toward violence and beliefs
      of contextual justification of wife abuse among Syrian medical and nursing
      students. DESIGN: A descriptive, cross-sectional design was used. The Perceptions
      of and Attitudes toward Wife Abuse Questionnaire was used to collect data from a
      convenience sample of 621 medical and nursing students from three public
      universities in Syria. RESULTS: Only 18.4% of the students had positive attitudes
      toward interpersonal violence reflecting low tolerance to wife beating and use of
      physical force for problem solving and child discipline, and 16.1% did not
      justify wife beating. Medical, older, female students, from urban areas, with
      more educated parents, and those who did not experience violence or witness
      violence between their parents had significantly more positive attitudes toward
      wife abuse and significantly less justification of wife beating (p < .05).
      CONCLUSION AND IMPLICATIONS: Education about violence against women of future
      medical and nursing students is the responsibility of medical and nursing
      educators and health policy makers, who have to acknowledge the influence of the
      sociocultural factors in shaping student's attitudes toward wife abuse and
      develop strategies to enhance these attitudes at the early stages of professional
      preparation.

PMID- 22477721
TI  - Acculturation and health status among Hispanic American elders.
AB  - PURPOSE: Hispanic Americans are at risk for health-related problems. Disparities
      in diseases such as diabetes and obesity, poor access to health services, and
      lack of health insurance have placed Hispanic Americans at a disadvantage.
      Sociocultural factors such as acculturation and its relationship to health
      require further investigation. The primary purpose of this study was to identify
      the relationship between acculturation and health in Hispanic American elders and
      examine the interrelationships of acculturation, health status, age, gender,
      education, years in the United States, and income. DESIGN: This descriptive
      correlational study was a secondary analysis of data from a large study titled
      Culture Bias in Testing Expressive Ability in Dementia. METHODS: A total sample
      of 132 community-dwelling Hispanic American elders was used. The Cross Cultural
      Measure of Acculturation was used to measure acculturation, and health status was
      measured using the SF-8(r) Health Survey. Correlation and multiple linear
      regressions were used to analyze the data. DISCUSSION/CONCLUSIONS: Findings from
      the study revealed that participants who were more acculturated to mainstream
      American culture reported their mental health to be better but not their physical
      health. This is an important contribution to advancing knowledge about cultural
      and health issues among Hispanic American elders, with implications for the
      clinical setting and for providing more culturally competent care.

PMID- 22477722
TI  - Respect, protection, faith, and love: major care constructs identified within the
      subculture of selected urban African American adolescent gang members.
AB  - PURPOSE: The purpose of this study was to discover universal and diverse care
      meanings and expressions of the selected urban African American adolescent gang
      culture within a qualitative paradigm. DESIGN: The study was conducted using
      ethnonursing research methodology and was guided by Leininger's theory of culture
      care. Thirteen key participants and 28 general participants were selected from a
      school setting in a Midwestern city. Data were collected and analyzed over a 12
      month period, in which the researcher participated daily in school and
      extracurricular activities of the gang members. Leininger's Data Analysis Guide
      included collection of raw data and maintenance of a field journal, coding and
      examining of the data for behavioral patterns and structural meanings, and
      finally formulation of major themes. FINDINGS: Culture care constructs that
      emerged from the major themes were respect, being listened to/accepted,
      worthiness, concern for others, protection, surveillance, trust, and faith.
      CONCLUSIONS: Nurses may promote health and well-being through collaborative
      partnerships with gang members and working with other caregivers to encourage
      more healthy lifestyles. Nurses should assume a leadership role in restructuring
      health policy that would give equal voice to underprivileged members of American
      society.

PMID- 22477723
TI  - Immunohistochemical investigation of F344/N rat islet cell tumors from national
      toxicology program studies.
AB  - In this study, we have investigated the immunoexpression of peptide hormones and
      mediators associated with human islet cell tumors in a group of proliferative
      islet cell lesions in F344 rats including islet cell hyperplasias, adenomas, and
      carcinomas, as defined by conventional histopathologic criteria. All
      proliferative islets expressed synaptophysin, although decreased expression
      intensity was observed in hyperplasias and adenomas. Most of the proliferative
      lesions expressed insulin, which generally decreased as lesions progressed toward
      malignancy. The distribution of glucagon, somatostatin, and gastrin-expressing
      cells was altered in proliferative islet lesions but did not comprise a large
      proportion of cells. Islet cell tumors were associated with increased nuclear
      expression of cyclin-dependent kinase 4 as well as increased proliferating cell
      nuclear antigen and decreased beta-catenin expression. c-Myelocytomatosis
      oncogene expression was variable. This is the first study to describe the
      immunophenotype of islet cell tumors in the F344 rat and to show that islet cell
      tumors in the F344 rat exhibit similarities in protein expression to the human
      counterpart.

PMID- 22477724
TI  - Lapatinib for advanced or metastatic breast cancer.
AB  - Lapatinib is a potent reversible and selective inhibitor of the tyrosine kinase
      domains of epidermal growth factor receptor and human epidermal growth factor
      receptor (HER)-2 that exerts its action by competitive binding to the
      intracellular ATP-binding site of the receptor. It is registered for the
      treatment of advanced or metastatic HER-2+ breast cancer in combination with
      capecitabine and for hormone receptor-positive breast cancer in combination with
      an aromatase inhibitor. Lapatinib administered orally once daily is moderately to
      well tolerated, with rash and gastrointestinal adverse events as the main
      toxicities. In studies on the efficacy of lapatinib, direct comparisons between
      lapatinib and trastuzumab are lacking. Results of ongoing randomized phase III
      studies with lapatinib or trastuzumab in combination with taxanes as first-line
      agents for metastatic breast cancer as well as in the neoadjuvant and adjuvant
      settings are awaited.

PMID- 22477725
TI  - Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen
      4: challenges from a new cause of a rare disease.
AB  - Specific human monoclonal antibodies antagonize cytotoxic T-lymphocyte antigen 4
      (anti-CTLA-4 mAbs), a negative regulator of the immune system, inducing
      unrestrained T-cell activation. In patients with advanced or metastatic melanoma,
      one of these agents, ipilimumab, produced considerable disease control rates and,
      for the first time, a clear improvement in overall survival outcomes. However,
      accumulating clinical experience with anti-CTLA-4 mAbs identified a novel
      syndrome of autoimmune and autoinflammatory side effects, designated as "immune
      related adverse events," including mainly rash, colitis, and hepatitis.
      Autoimmune hypophysitis has emerged as a distinctive side effect induced by anti
      CTLA-4 mAbs. This condition may be life threatening because of adrenal
      insufficiency if not promptly recognized, but it may easily be diagnosed and
      treated if clinically suspected. Hypopituitarism caused by these agents is rarely
      reversible and prolonged or life-long substitutive hormonal treatment is often
      required. The precise mechanism of injury to the pituitary triggered by anti-CTLA
      4 mAbs is yet to be fully elucidated.

PMID- 22477726
TI  - Bevacizumab-based therapies in the first-line treatment of metastatic colorectal
      cancer.
AB  - Since its approval for the first-line treatment of metastatic colorectal cancer
      (mCRC), bevacizumab has become a standard treatment option in combination with
      chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in
      combination with a number of different backbone chemotherapy regimens, and its
      widespread use has introduced several important questions regarding the selection
      and optimization of bevacizumab-based treatment regimens, its use in various
      patient populations, and the identification of associated adverse events. This
      review discusses the results of several phase II and phase III clinical trials,
      as well as large observational studies, to address the use of bevacizumab in the
      treatment of patients with mCRC in the first-line setting.

PMID- 22477727
TI  - The European Medicines Agency review of cabazitaxel (Jevtana(r)) for the
      treatment of hormone-refractory metastatic prostate cancer: summary of the
      scientific assessment of the committee for medicinal products for human use.
AB  - On March 17, 2011 the European Commission issued a marketing authorization valid
      throughout the European Union for Jevtana(r) (Sanofi-Aventis, Paris, France) for
      the treatment of patients with hormone-refractory metastatic prostate cancer
      previously treated with a docetaxel-containing regimen. The active substance of
      Jevtana(r) is cabazitaxel acetone solvate, an antineoplastic agent that acts by
      disrupting the microtubular network in cells. The recommended dose of cabazitaxel
      is 25 mg/m2 administered as a 1-hour i.v. infusion every 3 weeks in combination
      with oral prednisone or prednisolone, 10 mg, administered daily throughout
      treatment. In the main study submitted for this application, a 2.4-month longer
      median overall survival time and a 30% lower risk for death were observed for
      cabazitaxel, compared with mitoxantrone. The most common side effects with
      cabazitaxel were anemia, leukopenia, neutropenia, thrombocytopenia, and diarrhea.
      This paper summarizes the scientific review of the application leading to
      approval in the European Union. The detailed scientific assessment report and
      product information, including the summary of product characteristics, are
      available on the European Medicines Agency Web site (http://www.ema.europa.eu).

PMID- 22477729
TI  - Taking stock.

PMID- 22477728
TI  - Accumulating evidence for a drug-drug interaction between methotrexate and proton
      pump inhibitors.
AB  - BACKGROUND: A number of medications are known to interact with methotrexate
      through various mechanisms. The aim of this article is to apprise practitioners
      of a new labeling change based on the accumulating evidence for a possible drug
      drug interaction between methotrexate (primarily at high doses) and proton pump
      inhibitors (PPIs). METHODS: The U.S. Food and Drug Administration (FDA) Adverse
      Event Reporting System (AERS) database of spontaneous adverse event reports and
      the published literature were searched for cases reporting an interaction between
      methotrexate and PPIs. RESULTS: A search of the AERS database and existing
      literature found several individual case reports of drug-drug interactions and
      three additional supportive studies that suggest potential underlying mechanisms
      for the interaction. CONCLUSION: There is evidence to suggest that concomitant
      use of methotrexate (primarily at high doses) with PPIs such as omeprazole,
      esomeprazole, and pantoprazole may decrease methotrexate clearance, leading to
      elevated serum levels of methotrexate and/or its metabolite hydroxymethotrexate,
      possibly leading to methotrexate toxicities. In several case reports, no
      methotrexate toxicity was found when a histamine H2 blocker was substituted for a
      PPI. Based on the reviewed data, the FDA updated the methotrexate label to
      include the possible drug-drug interaction between high-dose methotrexate and
      PPIs. Physicians should be alerted to this potential drug-drug interaction in
      patients receiving concomitant high-dose methotrexate and PPIs.

PMID- 22477730
TI  - Surgical ablation of hepatocellular carcinoma with 2.45-GHz microwave: a critical
      appraisal of treatment outcomes.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a new generation of 2.45-GHz
      microwave to ablate hepatocellular carcinoma by surgical approach. DESIGN; Case
      series with prospective follow-up. SETTING: A university teaching hospital in
      Hong Kong. PATIENTS: From March 2009 to January 2011, 26 consecutive patients (19
      men and 7 women) with a median age of 63 (range, 49-79) years with hepatocellular
      carcinoma were recruited. Five (19%) of the patients had recurrent hepatocellular
      carcinoma after previous treatment. INTERVENTION: Microwave ablation for
      hepatocellular carcinomas (one tumour, n=24; two tumours, n=2) using a
      laparoscopic (n=16) or open approach (n=10). MAIN OUTCOME MEASURES: Operative
      mortality and morbidity, rate of incomplete ablation, recurrence rate, and
      survival rate. RESULTS: The median tumour diameter was 3.8 cm (range, 2.0-6.0
      cm). Complications occurred in five (19%) of the patients; only one was ablation
      related, and there was no operative mortality. One (4%) of the patients
      experienced incomplete ablation. Recurrent tumours were noted in 11 (42%) of the
      patients (5 were local, 2 were remote, and 4 were multifocal) after a median
      follow-up of 14 (range, 4-26) months. The failure rate for local disease control
      was 23%, and was 14% if patients with recurrent hepatocellular carcinoma were
      excluded. All but one patient survived until the time of censorship. The mean
      survival was 25 (standard deviation, 1) months. CONCLUSION: This new-generation
      microwave technique is safe and effective for local ablation of hepatocellular
      carcinoma. It is a valuable treatment option for patients who are not candidates
      for hepatectomy.

PMID- 22477731
TI  - Is stroke thrombolysis safe and efficacious in Hong Kong?
AB  - OBJECTIVE: To investigate the safety and efficacy of stroke thrombolysis in a
      local hospital. DESIGN: Historical cohort study. SETTING: A tertiary hospital in
      Hong Kong. PATIENTS: The outcome of acute ischaemic stroke patients treated with
      intravenous tissue plasminogen activator between October 2008 and May 2011 was
      compared to those admitted during the same period who were thrombolysis-eligible,
      but treated conservatively due to unavailability of the thrombolysis service
      after-hours. INTERVENTIONS: Intravenous tissue plasminogen activator. MAIN
      OUTCOME MEASURES: Primary outcome was functional independence (modified Rankin
      Scale score of 2 or below) at 3 months. Safety outcomes were symptomatic
      intracranial haemorrhage and 3-month mortality. Secondary outcomes were hospital
      length of stay, direct home discharge, and nursing home discharge. RESULTS: A
      total of 48 thrombolysis and 63 non-thrombolysis patients were identified. Fifty
      two percent of the thrombolysis group achieved functional independence compared
      to 24% of non-thrombolysis group (P=0.003), without significant increase in
      mortality (15% vs 13%, P=0.51) or symptomatic intracranial haemorrhage (4% vs 2%,
      P=0.58). Twenty-nine percent of the thrombolysis group patients were discharged
      home directly, versus 6% of non-thrombolysis group (P<0.001). Mean length of stay
      was shorter for the thrombolysis group (25 vs 35 days; P=0.034). A similar
      percentage from each group was discharged to nursing homes. CONCLUSION:
      Implementation of the stroke thrombolysis service in Hong Kong appeared safe and
      efficacious. Patients who received thrombolysis had better outcomes compared to
      non-thrombolysis cohort. Further studies are needed to investigate the economics
      of stroke thrombolysis in Hong Kong, which may help to improve funding for
      provision of this service.

PMID- 22477732
TI  - Factors influencing the mode of delivery and associated pregnancy outcomes for
      twins: a retrospective cohort study in a public hospital.
AB  - OBJECTIVES: To determine current trends for different modes of delivery in twin
      pregnancies, factors affecting the mode of delivery, and associated outcomes.
      DESIGN: Retrospective cohort study. SETTING: A public hospital in Hong Kong.
      PARTICIPANTS: All twin pregnancies booked at Kwong Wah Hospital during a 3-year
      period from 1 April 2006 to 31 March 2009. RESULTS: Of 197 sets of twins, 35
      (18%) were delivered vaginally and 162 (82%) by caesarean section (47% were
      emergencies and 53% elective). In all, 32 (37%) of the elective and 21 (28%) of
      the emergency caesarean sections were in response to maternal requests. Vaginal
      delivery was more common in mothers with a history of vaginal delivery and
      monochorionic diamniotic twins. Women who conceived by assisted reproduction or
      those who had a tertiary education were more likely to deliver by caesarean
      section. The type of conception and the presentation of the second twin were
      statistically significant factors affecting maternal choice on the mode of
      delivery. Maternal age did not affect the choice of delivery mode. Except for the
      higher frequency of sepsis and cord blood acidosis in second twins delivered
      vaginally, there were no significant differences in neonatal morbidity between
      the groups that attempted vaginal delivery or requested caesarean sections. All
      the women who had compression sutures or hysterectomy to control massive
      postpartum haemorrhage were delivered by caesarean section. CONCLUSION: A high
      caesarean section rate observed in our cohort was associated with maternal
      requests for this mode of delivery. The type of conception and the presentation
      of the second twin were statistically significant factors affecting maternal
      choice on mode of delivery. Women's requests for caesarean delivery out of the
      concern for their babies are not supported by current evidence. In response to a
      woman with a twin pregnancy requesting caesarean delivery, the pros and cons of
      vaginal deliveries and caesarean sections should be fully explained before the
      woman's autonomy is respected.

PMID- 22477733
TI  - Tight control early rheumatoid arthritis clinic in Hong Kong: a pilot study.
AB  - OBJECTIVE: To evaluate disease activity in early rheumatoid arthritis patients in
      daily practice 1 year after applying a tight control treatment strategy aimed at
      lowering disease activity (Disease Activity Score 28, <= 3.2). DESIGN: Single-arm
      open trial with historical controls. SETTING: Regional hospital, Hong Kong.
      PATIENTS: All new rheumatoid arthritis patients (onset < 2 years) attending the
      tight control clinic from October 2008 to October 2009 were recruited. All the
      patients were followed up every 3 to 6 weeks and clinically assessed using the
      Disease Activity Score 28. Disease-modifying agent treatment was stepped up
      according to a preset protocol ladder and patient tolerance. The treatment target
      was to achieve a Disease Activity Score 28 of 3.2 or below (low disease
      activity). These patients were compared to matched historical controls in the
      rheumatology clinic. RESULTS: Twenty patients in the tight control early
      rheumatoid arthritis clinic were recruited. Their disease activities were brought
      into better control than historical control patients who were followed up every
      12 weeks. At week 52, clinical variables showed greater improvements in the
      intensive care group; respective mean scores (based on the Disease Activity Score
      28 system) were 2.7 versus 4.2 (P<0.001); respective mean Health Assessment
      Questionnaire scores were 0.2 versus 1.3 (P<0.001). CONCLUSION: Outcomes of
      patients attending our locally adapted tight control clinic were consistent with
      previous reports in the literature. The clinic reduced rheumatoid arthritis
      activity faster and better. It entailed more frequent follow-up and monitoring,
      however. To address this strategy more objectively, a randomised trial with
      parallel controls is necessary.

PMID- 22477734
TI  - Acute and subacute inflammation of the optic nerve and its sheath: clinical
      features in Chinese patients.
AB  - OBJECTIVE: Inflammation of the optic nerve (optic neuritis) and its sheath (optic
      perineuritis) can have similar initial clinical presentations. They are less well
      defined in the Chinese than in Caucasians, and the aetiology of optic neuritis
      may also differ depending on ethnicity. The aim of our study was to document the
      clinical features of acute/subacute optic neuritis/optic perineuritis in Chinese
      patients. DESIGN: Retrospective case series. SETTING: Hong Kong Eye Hospital,
      Hospital Authority. PATIENTS: Records of all patients presenting to the Hong Kong
      Eye Hospital between 2005 and 2008, with their first episode of optic
      neuritis/optic perineuritis with onset of symptoms within 30 days, were reviewed.
      MAIN OUTCOME MEASURES: Disease aetiology, clinical features and outcomes.
      RESULTS: Twenty-nine patients were included (M:F=13:16), with a mean age of 46
      years at presentation. Among these, 25 had optic neuritis and four had optic
      perineuritis; four presented with bilateral optic neuritis. Among the optic
      neuritis group, 17 (68%) were idiopathic, seven (28%) were related to multiple
      sclerosis, and one (4%) had neuromyelitis optica. Poor visual outcome in the
      optic neuritis group was associated with poor visual acuity at presentation and
      poor visual acuity at the nadir. CONCLUSION: Optic perineuritis and neuromyelitis
      optica-related optic neuritis were more commonly encountered in our study of Hong
      Kong Chinese patients than in Caucasian populations. Even in Chinese patients
      with 'typical' optic neuritis, neuro-imaging and further investigations may be
      warranted to exclude optic perineuritis/neuromyelitis optica, since Chinese
      ethnicity is itself an atypical feature. Where neuro-imaging is not readily
      available, intravenous methylprednisolone may be considered as initial treatment
      to cover both optic neuritis/optic perineuritis in patients with severe visual
      loss.

PMID- 22477735
TI  - The Chinese version of the pelvic pain and urgency/frequency symptom scale: a
      useful assessment tool for street-ketamine abusers with lower urinary tract
      symptoms.
AB  - OBJECTIVE: To investigate the use of a translated Chinese version of the pelvic
      pain and urgency/frequency symptom scale as an assessment and prognostic tool to
      evaluate the severity of street-ketamine-associated lower urinary tract symptoms
      and their reversibility after abstinence. DESIGN: Cross-sectional study. SETTING:
      A special designated out-patient clinic in a regional hospital in Hong Kong.
      PARTICIPANTS: There were 50 patients with street-ketamine-associated lower
      urinary tract symptoms and 20 healthy individuals. MAIN OUTCOME MEASURES:
      Reliability and validity of the questionnaire; frequency of individual lower
      urinary tract symptoms, cystoscopic, urodynamic and radiological abnormalities,
      and their correlation with pelvic pain and the urgency/frequency score. RESULTS:
      The test-retest reliability coefficient was 0.755 (P<0.001). Cronbach's alpha was
      0.974. Mann-Whitney U test proved the discriminatory ability of the questionnaire
      (P<0.001). Patients with specific lower urinary tract symptoms had a higher mean
      pelvic pain and urgency/frequency total score compared to those without them:
      frequency (23.8 vs 17.3), nocturia (22.4 vs 14.0), urgency (22.5 vs 15.1),
      dysuria (22.7 vs 13.3), and haematuria (24.8 vs 16.2). The number of daytime
      voids and nocturia episodes correlated well with pelvic pain and
      urgency/frequency scores. With an increasing score, the likelihood of having
      cystitis changes, urodynamic abnormalities and hydronephrosis increased, while
      the cystometrically determined bladder capacity decreased. None of the patients
      with a score of 16 or below had urodynamic abnormality or hydronephrosis. The
      mean score change in the abstinence group was -4.33, versus +3.33 in their
      counterparts. CONCLUSIONS: The Chinese version of the pelvic pain and
      urgency/frequency questionnaire is reliable and valid for assessment in patients
      with street-ketamine-associated lower urinary tract symptoms. The pelvic pain and
      urgency/frequency score correlates well with symptom severity as well as
      endoscopic, urodynamic and radiological abnormalities in patients with street
      ketamine-associated lower urinary tract symptoms. A cut-off total pelvic pain and
      urgency/frequency score of 17 may suggest more serious urological sequelae from
      ketamine abuse. Abstinence from ketamine reduced lower urinary tract symptoms,
      but the extent of reversibility of urinary tract damage is yet to be evaluated.

PMID- 22477736
TI  - Epidemiology of occupational hand injury in Hong Kong.
AB  - OBJECTIVES: To study the epidemiology of occupational hand injuries and
      associated social and industrial factors. DESIGN. For this retrospective case
      series of patients with occupational hand injuries, case records were retrieved
      to gather data. In addition, all the subjects were interviewed by a single
      interviewer using a predesigned questionnaire. SETTING: Division of Hand Surgery,
      Department of Orthopaedics and Traumatology, Queen Mary Hospital, Hong Kong.
      PATIENTS: A total of 250 patients with occupational hand injuries were treated
      during the period from 1999 to 2001. This period was chosen to obtain 10 years of
      follow-up data to assess return to work and any secondary injuries. MAIN OUTCOME
      MEASURES: Personal particulars (gender, age, marital status, education level,
      length of stay in Hong Kong, type of employment, wage system, personal habits,
      family size, number of breadwinners, income), type of industry and mode of
      injury, causes of injury according to the worker, work conditions, type of
      injury, and treatment given. RESULTS: Two groups of workers in our study had more
      occupational hand injuries, namely those with less than 1 year of experience on a
      new job and immigrants from China. Factors associated with a large proportion of
      occupational hand injuries were male gender with personal risk factors (smoking
      and regular consumption of alcohol, long working hours), and in the case of
      machine operators, inadequate training and use of safety devices. CONCLUSION:
      Occupational hand injuries lead to loss of working hours and compensation. For
      prevention, the workplace should be made into a safer and work-friendly
      environment. Workers should also have sufficient training.

PMID- 22477737
TI  - Workshop 5--Sources of bias in cohort studies.

PMID- 22477738
TI  - Medication-induced acute angle closure attack.
AB  - OBJECTIVE: To review acute angle closure attacks induced by local and systemic
      medications. DATA SOURCES: PubMed literature searches up to August 2011. STUDY
      SELECTION: The following key words were used for the search: "drug",
      "iatrogenic", "acute angle closure glaucoma". DATA EXTRACTION: A total of 86
      articles were retrieved using the key words. Only those concerning acute angle
      closure attack triggered by local or systemic drug administration were included.
      For articles on the same or related topics, those published at later or more
      recent dates were selected. As a result, 44 articles were included and formed the
      basis of this review. DATA SYNTHESIS: An acute attack of angle closure can be
      triggered by dilatation of the pupil, by anatomical changes in the ciliary body
      and iris, or by movement of the iris-lens diaphragm. Local and systemic
      medications that cause these changes have the potential to precipitate an attack
      of acute angle closure. The risk is higher in subjects who are predisposed to the
      development of angle closure. Many pharmaceutical agents including ophthalmic
      eyedrops and systemic drugs prescribed by general practitioners and various
      specialists (in psychiatry, otorhinolaryngology, ophthalmology, medicine, and
      anaesthesia) can precipitate an acute angle closure attack. The medications
      include: anti-histamines, anti-epileptics, antiparkinsonian agents,
      antispasmolytic drugs, mydriatic agents, sympathetic agents, and botulinum toxin.
      CONCLUSION: Since acute angle closure attack is a potentially blinding eye
      disease, it is extremely important to be vigilant and aware of ophthalmic and
      systemic medications that can lead to such attacks in predisposed subjects and to
      diagnose the condition when it occurs.

PMID- 22477739
TI  - Prenatal diagnosis and assessment of facial clefts: where are we now?
AB  - Orofacial clefts are one of the most common non-syndromic congenital structural
      abnormalities. Prenatal diagnosis of such defects has traditionally been made by
      ultrasound examination. With the advent of routine second-trimester ultrasound
      screening for morphological abnormalities in the recent two decades, the prenatal
      detection rate of such abnormalities has progressively increased. While
      conventionally, two-dimensional scanning has been used for screening of lip
      clefts, the development of three-dimensional ultrasound scanning technology has
      allowed more easy visualisation of the defects, as well as more accurate
      evaluation of palatal clefts. Various three-dimensional scanning techniques to
      assess such defects have been advocated in the recent 5 to 6 years, but as yet
      there is no consensus as to the most effective and practical methods. As fetal
      magnetic resonance imaging gradually becomes an accessible modality of imaging in
      modern obstetrics, it is likely to become an additional tool to assess these
      defects.

PMID- 22477740
TI  - Benign metastasising leiomyoma after hysterectomy and bilateral salpingo
      oophorectomy.
AB  - Benign metastasising leiomyomatosis is a rare condition affecting women in the
      reproductive age-group with a history of uterine fibroids, who have undergone
      treatment by myomectomy or hysterectomy. It is characterised by development of
      multiple, indolent, smooth muscle tumours outside the uterus, most commonly in
      the lungs, and manifests several years after the uterine surgery. We describe the
      case of a young woman, who had undergone total abdominal hysterectomy and
      bilateral salpingo-oophorectomy for multiple fibroids and a right ovarian cyst.
      After 5 years of being on oestrogen replacement therapy, she was detected to have
      benign metastasising leiomyoma, for which an additional laparotomy was performed.
      At laparotomy, removal of the pelvic mass was associated with several
      complications. The metastatic lesions in the lung responded well to progestogens
      (megestrol acetate) alone as evidenced by regression of the lesions detected at
      follow-up after 6 months and 1 year.

PMID- 22477741
TI  - Intrapleural injection of OK-432 as the primary in-utero treatment for fetal
      chylothorax.
AB  - Chylothorax is a rare congenital condition associated with significant perinatal
      mortality and morbidity. Previous treatments with repeated thoracocentesis or
      thoracoamniotic shunting were technically demanding, and associated with
      significant procedure-related complications and neonatal complications. Here we
      report the first successful case in Hong Kong treated by a simple and effective
      intervention, namely pleurodesis with OK-432, in a fetus presenting at 20 weeks
      of gestation with bilateral pleural effusion.

PMID- 22477742
TI  - Acute torsion of a wandering spleen.
AB  - The 'wandering spleen' is a rare condition due to extreme laxity or absence of
      ligaments that fix the organ in its normal anatomical position within the left
      upper quadrant. Without early surgical intervention, wandering spleen can lead to
      torsion and subsequent splenic infarction or rupture. Clinical suspicion plus
      urgent investigation and intervention are important, so as to salvage the spleen
      and prevent complications. We present a case of torsion of a wandering spleen in
      a 21-year-old young woman, who presented with a painful pelvic mass. We also
      reviewed the literature on this entity.

PMID- 22477743
TI  - A pale Chinese boy with recurrent painful digital swelling.
AB  - Thalassaemia is the most common haemoglobinopathy in the Chinese population.
      However, recurrent painful digital swelling is not a typical manifestation of
      this well-known hereditary condition. We describe a case of co-inheritance of
      beta-thalassaemia and sickle cell trait in a Chinese family and a child who
      suffered from sickle cell/beta-thalassaemia with recurrent dactylitis. This
      report highlights awareness of this rare condition in the Chinese population,
      since acute manifestations can be life-threatening and mimic other emergency
      conditions. Prompt management can prevent further complications and avoid
      unnecessary interventions due to delay in diagnosis. A detailed family history
      and examination of the patient's peripheral blood smear is crucial to reach a
      correct diagnosis.

PMID- 22477744
TI  - Hong Kong dollar in the oesophagus.

PMID- 22477745
TI  - Family medicine internship training: importance for Hong Kong's primary care.

PMID- 22477746
TI  - Thrombolytic service of acute ischaemic stroke in Hong Kong.

PMID- 22477747
TI  - Contraction of the Amplatzer Vascular Plug I and II in pulmonary artery and
      systemic venous collateral vessels is safe and of no hemodynamic or vascular
      consequence in short- and mid-term follow-up.
AB  - BACKGROUND: The Amplatzer Vascular Plug (AVP) I and AVP II have been used
      successfully to occlude moderate-large venous collateral vessels (VC) and
      pulmonary arteriovenous malformations (PAVM) in children and adults with
      congenital heart disease. PURPOSE: To report our experience in 4 patients who
      underwent device occlusion of systemic venous collaterals (3 patients) and device
      closure of pulmonary arteriovenous malformation (1 patient) that developed
      contraction of the AVP. METHODS: The records of all patients who underwent device
      occlusion utilizing both AVP I and AVP II between November 2006 and January 2011
      were retrospectively reviewed. All available follow-up chest x-rays were reviewed
      and compared with angiograms obtained post device occlusion. A device 30%-50%
      larger than the targeted vessel was utilized to occlude the vessel. RESULTS: Four
      patients were identified with a mean age of 21 years (range, 7 years and 2 months
      52 years) and mean weight of 60.6 kg (range, 15.3-131.5 kg). Two patients
      received AVP I and 2 patients received AVP II. One patient who received the 12 mm
      AVP I showed moderate contraction. The 3 other patients who received AVP I (6 mm)
      and AVP II (10 mm, 12 mm) all demonstrated device contraction to the original
      shape of the device. Mean follow-up time of 24 months (range, 12-40 months) has
      shown no evidence of hemodynamic or vascular compromise. CONCLUSIONS: Short to
      mid-term follow-up indicate that contraction of AVP I and AVP II is safe with no
      evidence of hemodynamic or vascular compromise. Continued long-term follow-up is
      warranted.

PMID- 22477748
TI  - Good efficacy of drug-eluting balloons in a mixed population of patients with
      coronary artery disease.
AB  - INTRODUCTION: Drug-coated balloons (DCB) are being increasingly used in
      interventional cardiology and are established for the treatment of in-stent
      restenosis (ISR). It is unclear how effective they are in patients with de novo
      lesions. METHODS: A prospective registry of patients treated with the In.Pact DCB
      at our institution was conducted. Patients with ISR and those with planned
      surgery or contraindication to long-term use of double-antiplatelet therapy were
      included. OUTCOME MEASURES: 12-month rates of clinically driven target-lesion
      revascularization (TLR). The efficacy of DCB was compared between patients with
      ISR and de novo lesions and in those with reference vessel diameter (RVD) < and >
      2.75 mm. RESULTS: A total of 139 patients (222 lesions) were followed up for 12
      months. The mean age was 69 +/- 10 years. Ninety-five patients (68%) had stable
      angina and 44 patients (32%) had acute coronary syndrome. Clinically driven TLR
      was performed in 6/126 lesions (4.8%) in the de novo group and in 5/92 lesions
      (5.4 %) in the ISR group (P=1.0). In the de novo group, TLR rate was 1/45 (2.2%)
      in patients with vessel diameter >2.75 mm and 5/81 (6.2%) in those with diameter
      <2.75 (P=.42). In the ISR group, TLR was 3/71 (4.2%) in patients with vessel
      diameter >2.75 mm and 2/21 (9.5%) in those with diameter <2.75 mm (P=.32).
      CONCLUSIONS: DCB are a valuable treatment option for patients with ISR offering
      good rates of TLR. Additionally, DCB can be an alternative to drug-eluting
      stents, if the use of long-term double antiplatelet medications is not desired.

PMID- 22477749
TI  - Low-dose unfractionated heparin administration during intravascular ultrasound
      studies is safe even shortly after endomyocardial biopsy in cardiac transplant
      patients.
AB  - BACKGROUND: Full therapeutic heparin doses ranging from 5000-10,000 units or
      weight based (70-100 units/kg) have been recommended during percutaneous coronary
      interventions. However, there are currently no data available in regards to the
      appropriate dosing of unfractionated heparin during intravascular ultrasound
      (IVUS) studies without therapeutic coronary interventions. The goal of this study
      was to evaluate the safety of low dose unfractionated heparin during IVUS
      studies, shortly after endomyocardial biopsy in cardiac transplant patients.
      METHODS: At the University of Arizona Medical Center, transplant patients
      routinely undergo diagnostic IVUS studies for the detection of early cardiac
      allograft vasculopathy (CAV) shortly after endomyocardial biopsy. A low-dose
      heparin (2000 to 3000 Units) is given before coronary wire and IVUS catheter
      advancement without checking activated clotting time. We evaluated the occurrence
      of any thromboembolic event or any other adverse outcomes in this population.
      RESULTS: A total of 108 cardiac transplant patients, who had underwent routine
      IVUS studies between 2004-2008 were identified retrospectively. The average
      heparin dose used was 2528 +/- 501 units. The left anterior descending artery was
      studied in 93% of cases. There was no thromboembolic event. Only one catheter
      induced coronary dissection occurred treated with percutaneous coronary
      intervention. An endomyocardial biopsy was performed 10-15 minutes before the
      administration of low-dose heparin. There were no other major adverse cardiac
      events in this population during the procedure. CONCLUSION: This is the first
      study showing the safety of low-dose heparin use during diagnostic IVUS studies
      in cardiac transplant patients, even shortly after endomyocardial biopsy.

PMID- 22477750
TI  - Heparin dose and harm: absence of evidence or evidence of absence?

PMID- 22477751
TI  - A novel method to deliver the Filtrap coronary embolic protection filter using a
      manual thrombectomy catheter: in vitro and in vivo comparison with the
      conventional method.
AB  - BACKGROUND: Although several types of distal embolic protection devices have been
      developed, they are usually difficult to use because of their stiff and bulky
      characteristics. We present a novel method to deliver the coronary embolic
      protection filter via a manual thrombectomy catheter. METHODS: We modified the
      Filtrap embolic protection filter (Nipro Corporation) to pass through the
      aspiration thrombectomy catheter. Three interventional cardiologists performed
      the Filtrap delivery with in vivo and in vitro coronary arteries using two
      different methods. The in vitro experiments were performed using a Circuit
      Cardiac Catheterization Simulator (Just Medical Corporation) with and without
      coronary artery stenosis. The in vivo experiment was performed using a normal pig
      coronary artery. The times required for Filtrap delivery in the two different
      methods were compared. The target lesions were the main and side branch of the
      left anterior descending, left circumflex, and right coronary arteries. RESULTS:
      The average Filtrap delivery time when using the thrombectomy catheter was
      significantly shorter compared to the time using the conventional method (in
      vitro experiment without coronary stenosis, 39 +/- 14 seconds vs 30 +/- 6 seconds
      and P=.019; in vitro experiment with multiple coronary stenosis, 69 +/- 55
      seconds vs 32 +/- 11 seconds and P=.012; in vivo experiment, 169 +/- 166 seconds
      vs 51 +/- 12 seconds; P=.019). CONCLUSION: The study results indicate that
      delivery of the coronary embolic protection filter via a manual thrombectomy
      catheter may simplify the procedure and decrease the procedure time.

PMID- 22477752
TI  - Percutaneous device closure of patent foramen ovale using the Premere occlusion
      device: initial experience, procedural, and intermediate-term results.
AB  - BACKGROUND: Percutaneous device closure is a therapeutic option in patients with
      presumed stroke complicating paradoxical emboli. Newer devices with lower
      profiles and potentially reduced thrombogenicity have emerged, such as the
      Premere PFO occlusion device (St Jude Medical, Inc.); there are limited data on
      the efficacy and procedural experience with this device. METHODS: We evaluated
      our initial experience with the Premere device in a contemporary patient cohort,
      comparing the procedural and intermediate follow-up characteristics with the
      currently utilized Amplatzer PFO occluder. RESULTS: Both devices were similarly
      effective in terms of immediate procedural success and defect closure. Procedures
      using the Premere device tended to be longer and required larger vascular access
      sheath sizes; there were also significantly more adverse events in the Premere
      group (4/29) compared to the Amplatzer group (0/42; P=.02), including 1
      retroperitoneal bleed, 2 hematomas, and 1 myocardial infarction. CONCLUSIONS:
      While the Amplatzer device may offer advantages in terms of safety and procedural
      simplicity, this in part reflects the early procedural experience with this new
      device. The Premere and Amplatzer PFO occlusion devices are similarly effective
      in achieving PFO closure when applied to appropriate anatomy and should be
      considered complementary when performing such procedures.

PMID- 22477753
TI  - Successful transfemoral antegrade valve-in-valve implantation of a SAPIEN XT
      valve into a degenerated mitral valve prosthesis.
AB  - Transfemoral aortic valve implantation has become an important interventional
      technique for patients with severe aortic stenosis and high surgical risks. The
      mitral valve has been a much greater challenge for interventional procedures, and
      no percutaneous mitral valve implantation system has yet been developed and
      approved. Here, we report the successful transfemoral, antegrade, valve-in-valve
      implantation of the SAPIEN XT valve (Edwards Lifesciences) into a degenerated
      mitral valve bioprosthesis. The patient was an 81-year-old woman with severe
      regurgitation of her 27 mm Epic mitral valve prosthesis (St. Jude Medical),
      suffering from dyspnea on mild exertion with a calculated logistic EuroScore of
      48% and an Society of Thoracic Surgeons score of 29%. Thus, another surgical
      mitral valve replacement was refused by the patient and was considered as
      extremely high risk by the cardiac surgeon. Therefore, a transfemoral valve-in
      valve implantation was planned. The femoral vein was used as an access site,
      followed by a transseptal puncture and placement of a super-stiff wire into the
      left ventricle. Then, the septum was dilated and a 26 mm SAPIEN XT valve was
      inserted through the septum and then inserted into the mitral valve prosthesis.
      Under rapid pacing, a very slow inflation of the balloon was performed, leading
      to a stable valve-in-valve implantation without any regurgitation. The patient
      was transferred to a normal ward after 2 days. This procedure is an off-label,
      technically very challenging, high-risk implantation that could be attempted in
      very select patients after discussion by a heart team and by experienced
      implanters.

PMID- 22477754
TI  - The incidence of transcatheter aortic valve implantation-related heart block in
      self-expandable Medtronic CoreValve and balloon-expandable Edwards valves.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been performed at
      Waikato Hospital for high-risk severe symptomatic aortic stenosis patients who
      are considered unsuitable for conventional cardiac surgery for the last 3 years.
      The Medtronic CoreValve (MCV) is a self-expandable device, while the Edwards
      SAPIEN valve (EV) requires the use of a balloon to expand the device. This
      observational study reports and compares the incidence of heart block in both
      Medtronic and Edwards transcatheter valves. METHODS: All patients who underwent
      TAVI between the periods of 28 August 2008 and 27 July 2011 were included in this
      study. Preprocedure and daily postprocedure until discharge electrocardiograms
      (ECG) were obtained prospectively. New onsets of significant atrioventricular
      (AV) and bundle branch blocks were recorded. Patients with existing pacemaker and
      those who did not survive the procedure were excluded. RESULTS: Sixty patients
      underwent TAVI during the study period, of whom 40 (67%) and 20 (33%) patients
      had MCV and EV implanted, respectively. Seven patients were excluded from the
      analysis; 38 MCV and 15 EV patients fulfilled the criteria for analysis. Mean age
      was 80 +/- 7 years, 57% were male. Five patients (9%) required permanent
      pacemaker (PPM) implantation, which occurred exclusively post MCV TAVI (MCV vs
      EV: 13% vs 0%, respectively; P=.02). The indications of PPM were complete heart
      block in 3 patients (60%), Mobitz II second-degree heart block in 1 patient
      (20%), and symptomatic sick sinus syndrome in 1 patient (20%). The incidence of
      left bundle branch block (LBBB) was increased after the TAVI procedure and was
      more significant with MCV implants (MCV vs EV: 42% vs 8%, respectively; P<.01).
      Of note, 2 of the 5 patients (40%) with pre-existing right bundle branch block
      (RBBB) who underwent TAVI required PPM (P=.01). CONCLUSION: MCV implantation is
      associated with a higher incidence of significant AV block requiring PPM
      implantation and LBBB compared to EV. The overall rate of PPM requirement post
      MCV TAVI is, however, lower than previously published data. Pre-existing RBBB may
      help in predicting the likelihood of developing significant AV block.

PMID- 22477755
TI  - Management of drug-eluting stent restenosis.
AB  - In-stent restenosis has been a longstanding problem after percutaneous coronary
      intervention. The introduction of the drug-eluting stent (DES) successfully
      reduced the rate of restenosis; however, it is not completely diminished.
      Although restenosis occurs less frequently compared to the bare-metal stent
      (BMS), DES restenosis remains a familiar problem due to the increasing total
      number of implanted DESs as well as the targeting of more complex lesions. In
      addition, worse outcomes after repeat revascularization compared to BMS
      restenosis are reported in DES restenosis. Management of DES restenosis is an
      emerging issue, which requires careful evaluation of the restenosed lesion,
      together with cautious determination of therapeutic strategy. In this review,
      available repeat revascularization procedures for DES restenosis as well as
      possible impacting factors on the outcomes are discussed.

PMID- 22477756
TI  - Bilateral arm approach for percutaneous coronary intervention of unprotected left
      main supported by a modified intra-aortic balloon pump.
AB  - Patients in whom femoral arterial access is not feasible pose a challenge in
      terms of hemodynamic support during high-risk percutaneous coronary intervention.
      Patient's height adds another challenge given the fixed lengths of available
      intra-aortic balloon pumps, in terms of achieving an adequate infrasubclavian
      positioning in the descending thoracic aorta. We report a case where a modified
      intra-aortic balloon pump helped achieve a successful result in a patient
      undergoing intervention of an unprotected left main using bilateral arm approach.

PMID- 22477757
TI  - Radial artery perforation during transradial catheterization managed with a
      coronary polytetrafluoroethylene-covered stent graft.
AB  - A 69-year-old man underwent transradial catheterization (TRC) with successful
      percutaneous coronary intervention (PCI), but developed a radial artery
      perforation. Guiding catheter re-positioning and prolonged balloon inflation were
      unable to provide hemostasis. Successful reconstruction of the perforated vessel
      required the unconventional and novel use of a coronary polytetrafluoroethylene
      covered stent graft.

PMID- 22477758
TI  - Rapid stent surface coverage after endothelial progenitor cell capture (genous)
      stent implantation: first optical coherence tomography report.
AB  - A 78-year-old man was referred for anterior wall motion abnormality on
      echocardiogram. In anticipation of the urgent surgery for stomach cancer, an
      endothelial progenitor cell Genous capture stent (Orbus Neich Medical Technology)
      was implanted. After 2 weeks, optical coherence tomography was done to confirm
      the coverage of stent struts and all struts were fully covered by
      reendothelialization. The patient could undergo stomach surgery without
      antiplatelet therapy successfully.

PMID- 22477759
TI  - Acute ST-elevation myocardial infarction 6 years following a sirolimus-eluting
      stent secondary to complete stent fracture.
AB  - With increasing coronary interventions, coronary stent fracture following
      implantation of drug-eluting stents is being commonly recognized. Though isolated
      strut fractures are often only incidental findings, more severe forms of stent
      fracture with complete transection have adverse clinical outcomes. Most such
      cases are reported within several months following the index angioplasty. We
      report an unusual presentation of late stent fracture following a sirolimus
      eluting stent, presenting with acute myocardial infarction 6 years after the
      initial stent implantation. The various mechanisms underlying fracture of drug
      eluting stents are reviewed. Because no known mechanisms were noted in our case,
      unknown factors may also play a role in the genesis of stent fracture. Clinicians
      need to be aware that such complications may present rarely, extremely late after
      the index procedure as an acute myocardial infarction.

PMID- 22477760
TI  - Single coronary artery anomaly: branching of left coronary artery from right
      coronary artery with 2 distinct patterns.
AB  - Normal coronary vasculature has a left coronary artery arising from the left
      coronary cusp and a right coronary artery arising from the right coronary cusp.
      In about 0.024% of cases in the general population, there is no left main
      coronary artery. In fact, there is a single coronary artery, which arises from
      the right coronary cusp. We encountered 2 such cases with distinct patterns. The
      first case was a patient with angina who had an abnormal stress test for which he
      underwent coronary angiography. This revealed a single coronary artery arising
      from the right coronary cusp. This vessel gave rise to the right coronary artery,
      which had a varicose anatomy, with a critical lesion in the posterior descending
      artery. The left coronary artery passed anteriorly to the pulmonary artery with a
      critical lesion in the circumflex artery. In the second case, the patient also
      had angina with a normal noninvasive work-up but due to his persistent symptoms,
      coronary angiography was performed. This revealed a single coronary artery
      arising from the right coronary cusp. Subsequent CT angiography revealed that the
      left coronary artery coursed in between the aorta and pulmonary artery without
      critical lesions. In both cases, the patients underwent coronary artery bypass
      grafting.

PMID- 22477761
TI  - Evaluation of endothelialization after percutaneous closure of paravalvular
      leaks.
AB  - BACKGROUND: There is limited data regarding the duration of endothelialization
      following paravalvular leak closure. We aimed to observe the endothelialization
      process in 2 patients who underwent surgery 6 and 16 months after failed
      percutaneous mitral paravalvular leak closure, respectively. METHODS:
      Twodimensional transesophageal echocardiography (2D-TEE) and real-time 3
      dimensional transesophageal echocardiography (RT-3D TEE) were utilized to
      demonstrate mitral paravalvular leaks. The status of endothelialization was
      explored in the surgery. RESULTS: Two patients underwent percutaneous closure of
      mitral paravalvular leaks both with 2 occluder devices. The first patient was
      admitted with dyspnea 6 months later. RT-3D TEE demonstrated a defect around the
      proximal part of one of the occluder devices. The residual mitral regurgitation
      was considered moderate to severe by 2D TEE and RT-3D TEE. The patient was
      referred to surgery in which failed endothelialization of both devices was
      observed. In the second patient, 2 occluder devices were implanted. He underwent
      surgery at 16 months due to progressive increase in the severity of mitral
      regurgitation, which disclosed partially endothelialized closure device.
      CONCLUSION: These cases suggest that endothelialization of closure devices may be
      significantly delayed or even absent for a long time following implantation.

PMID- 22477762
TI  - Percutaneous aortic balloon valvuloplasty performed in a patient with distal
      aortic occlusion.
AB  - We present a case of successful percutaneous aortic balloon valvuloplasty
      performed via surgical cut down of the right brachial artery in a patient with
      distal aortic occlusion. We describe the procedural technique and review the
      literature on alternative access sites that have been used to perform
      percutaneous aortic balloon valvuloplasty.

PMID- 22477763
TI  - Guideliner microcatheter to improve back-up support during a complex coronary
      stenting procedure through a tortuous left internal mammary graft.
AB  - Back-up support during percutaneous coronary interventions (PCI) is one of the
      keys for successful intervention. Extra back-up support guiding catheters, deep
      intubation, buddy wires, and other more complex techniques are usually used to
      improve this support. Left anterior descending (LAD) artery PCI through the left
      internal mammary artery (LIMA) are rarely performed because many operators feel
      reluctant to instrument a disease-free LIMA graft risking iatrogenic
      complications by passing wire, balloons, and stents to the diseased distal LAD.
      Improving back-up support during LIMA-LAD PCIs is often challenging because in
      this particular setting the distance between the LAD lesion and the guiding
      catheter is exceedingly long. We report a case of a challenging PCI of the LAD
      through a patent and disease-free LIMA graft. After multiple failed attempts to
      cross the LAD lesion with conventional stent deployment techniques, we
      successfully finished the stenting procedure using the Guideliner microcatheter
      (Vascular Solutions) as a guiding extension through the LIMA graft. With this
      case, we illustrate that this microcatheter dramatically improves the back-up
      support, allowing stent deployment also in very difficult settings as in tortuous
      LIMA grafts.

PMID- 22477764
TI  - Successful sealing of a coronary artery perforation with a mesh-covered stent.
AB  - Coronary artery perforation is a rare, but particularly feared and sometimes life
      threatening, complication of percutaneous coronary interventions. The incidence
      of coronary perforation has increased with newer, more invasive interventional
      devices and techniques like rotablation, excimer laser coronary angioplasty,
      routine high-pressure balloon dilatation, or chronic total occlusion
      interventions. Here we describe a case of Ellis grade 2 perforation following a
      balloon dilatation performed in an in-stent restenotic total occlusion. The
      perforation was successfully sealed with a recently introduced device, a mesh
      covered stent (MGuard stent, Inspire MD). This new stent is much more flexible
      than the polytetrafluoroethylene-covered stent, which is often implanted in Ellis
      2 or 3 grade perforations.

PMID- 22477765
TI  - Primary percutaneous coronary intervention in a case of idiopathic spontaneous
      coronary artery dissection.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare but important cause of
      acute coronary syndrome. SCAD can cause unstable angina, acute myocardial
      infarction, and sudden death. The diagnosis of coronary dissection is usually
      made by coronary angiography. Therapeutic options include medical therapy,
      percutaneous coronary intervention, and bypass surgery. A 23-year-old male
      patient presented with acute inferior wall myocardial infarction. He was taken
      for primary percutaneous coronary intervention and found to have long segment
      SCAD in the right coronary artery. He was stented with 2 drug-eluting stents;
      TIMI 3 flow was restored; and the patient had an uneventful, complete recovery.

PMID- 22477767
TI  - Odd electron diffraction patterns in silicon nanowires and silicon thin films
      explained by microtwins and nanotwins.
AB  - Odd electron diffraction patterns (EDPs) have been obtained by transmission
      electron microscopy (TEM) on silicon nanowires grown via the vapour-liquid-solid
      method and on silicon thin films deposited by electron beam evaporation. Many
      explanations have been given in the past, without consensus among the scientific
      community: size artifacts, twinning artifacts or, more widely accepted, the
      existence of new hexagonal Si phases. In order to resolve this issue, the
      microstructures of Si nanowires and Si thin films have been characterized by TEM,
      high-resolution transmission electron microscopy (HRTEM) and high-resolution
      scanning transmission electron microscopy. Despite the differences in the
      geometries and elaboration processes, the EDPs of the materials show great
      similarities. The different hypotheses reported in the literature have been
      investigated. It was found that the positions of the diffraction spots in the
      EDPs could be reproduced by simulating a hexagonal structure with c/a =
      12(2/3)(1/2), but the intensities in many EDPs remained unexplained. Finally, it
      was established that all the experimental data, i.e. EDPs and HRTEM images, agree
      with a classical cubic silicon structure containing two microstructural defects:
      (i) overlapping Sigma3 microtwins which induce extra spots by double diffraction,
      and (ii) nanotwins which induce extra spots as a result of streaking effects. It
      is concluded that there is no hexagonal phase in the Si nanowires and the Si thin
      films presented in this work.

PMID- 22477768
TI  - Constraints and restraints in crystal structure analysis.
AB  - The widely used restraint-based approach to structural analysis using diffraction
      data is critiqued. The convenience of using rigid constraints, through the use of
      internal coordinates, is discussed.

PMID- 22477766
TI  - Estimation of the effect of SLCO1B1 polymorphisms on lopinavir plasma
      concentration in HIV-infected adults.
AB  - BACKGROUND: The organic anion transporting polypeptides (OATP)/SLCO family
      represents an important class of hepatic drug uptake transporters that mediate
      the sodium independent transport of a diverse range of amphipathic organic
      compounds, including the protease inhibitors. The SLCO1B1 521T>C (rs4149056)
      single nucleotide polymorphism (SNP) has been consistently associated with
      reduced transport activity in vivo, and we previously showed an association of
      this polymorphism with lopinavir plasma concentrations. The aim of this study was
      to develop a population pharmacokinetic (PK) model to quantify the impact of
      521T>C. METHODS: A population PK analysis was performed with 594 plasma samples
      from 375 patients receiving lopinavir/ritonavir. Non-linear mixed effects
      modelling was applied to explore the effects of SLCO1B1 521T>C and patient
      demographics. Simulations of the lopinavir concentration profile were performed
      with different dosing regimens considering the different alleles. RESULTS: A one
      compartment model with first-order absorption best described the data. Population
      clearance was 5.67 l/h with inter-patient variability of 37%. Body weight was the
      only demographic factor influencing clearance, which increased 0.5 l/h for every
      10 kg increase. Homozygosity for the C allele was associated with a 37% lower
      clearance, and 14% for heterozygosity, which were statistically significant.
      CONCLUSIONS: These data show an association between SLCO1B1 521T>C and lopinavir
      clearance. The association is likely to be mediated through reduced uptake by
      hepatocytes leading to higher plasma concentrations of lopinavir. Further studies
      are now required to confirm the association and to assess the influence of other
      polymorphisms in the SLCO family on lopinavir PK.

PMID- 22477769
TI  - PDB_REDO: automated re-refinement of X-ray structure models in the PDB.
AB  - Structural biology, homology modelling and rational drug design require accurate
      three-dimensional macromolecular coordinates. However, the coordinates in the
      Protein Data Bank (PDB) have not all been obtained using the latest experimental
      and computational methods. In this study a method is presented for automated re
      refinement of existing structure models in the PDB. A large-scale benchmark with
      16 807 PDB entries showed that they can be improved in terms of fit to the
      deposited experimental X-ray data as well as in terms of geometric quality. The
      re-refinement protocol uses TLS models to describe concerted atom movement. The
      resulting structure models are made available through the PDB_REDO databank
      (http://www.cmbi.ru.nl/pdb_redo/). Grid computing techniques were used to
      overcome the computational requirements of this endeavour.

PMID- 22477770
TI  - Elastic constants of fibre-textured thin films determined by X-ray diffraction.
AB  - A new methodology is presented that allows the rapid determination of elastic
      constants of cubic fibre-textured thin films by X-ray diffraction. The
      theoretical concept is developed and tested on calculated examples of Cu and CrN
      films. The mechanical elastic constants are extrapolated from X-ray elastic
      constants by taking into consideration crystal and macroscopic elastic
      anisotropy. The derived algorithm enables the determination of a reflection and
      the corresponding value of the X-ray anisotropic factor Gamma for which the X-ray
      elastic constants are equal to their mechanical counterparts in the case of fibre
      textured cubic polycrystalline aggregates. The approach is independent of the
      crystal elastic anisotropy and depends on the fibre-texture type, the texture
      sharpness, the number of randomly oriented crystallites and the supposed grain
      interaction model. In the experimental part, out-of-plane Young's moduli of 111
      and 311 fibre-textured Cu and CrN thin films deposited on monocrystalline Si(100)
      substrates are determined. The moduli are extrapolated from thin-film
      experimental X-ray elastic constants that are determined by a combination of X
      ray diffraction substrate curvature and sin(2)psi methods. For the calculation,
      the film macroscopic elastic anisotropy (texture) is considered. The advantage of
      the new technique lies in the fact that experimental moduli are determined
      nondestructively, using a static diffraction experiment, and represent volume
      averaged quantities.

PMID- 22477771
TI  - The pseudo-single-crystal method: a third approach to crystal structure
      determination.
AB  - A novel method that enables single-crystal diffraction data to be obtained from a
      powder sample is presented. A suspension of LiCoPO(4) microrods was subjected to
      a frequency-modulated dynamic elliptical magnetic field to align the microrods;
      the alignment achieved was consolidated by photopolymerization of the suspending
      UV-curable monomer. The composite thus obtained (referred to as a pseudo single
      crystal) gave rise to X-ray diffraction data from which the crystal structure was
      solved using the standard method for single-crystal X-ray analyses. The structure
      determined was in good agreement with that reported using a conventional single
      crystal.

PMID- 22477772
TI  - Proliferation and skeletal myotube formation capability of C2C12 and H9c2 cells
      on isotropic and anisotropic electrospun nanofibrous PHB scaffolds.
AB  - This study aims at investigating the behavior in terms of the proliferation and
      skeletal muscle differentiation capability of two myoblastic cell lines, C2C12
      and H9c2, on both isotropic and anisotropic electrospun nanofibrous
      poly(hydroxybutyrate) (PHB) scaffolds, as well as on PHB films and polystyrene
      controls. After a careful characterization of the matrices in terms of surface
      morphology, surface roughness and mechanical properties, the proliferation rate
      and the capability of the two cell lines to form skeletal myotubes were
      evaluated. Genetic analyses were also performed in order to assess the
      differentiation level of the cells on the different substrates. We demonstrated
      that the aligned nanofibrous mesh decreases the proliferation activity and
      provides a higher differentiative stimulus. We also clarified how the nanofibrous
      substrate influences myotube formation, and quantified a series of myotube
      related parameters for both C2C12 and H9c2 cells.

PMID- 22477773
TI  - Crystallography Open Database - an open-access collection of crystal structures.
AB  - The Crystallography Open Database (COD), which is a project that aims to gather
      all available inorganic, metal-organic and small organic molecule structural data
      in one database, is described. The database adopts an open-access model. The COD
      currently contains ~80 000 entries in crystallographic information file format,
      with nearly full coverage of the International Union of Crystallography
      publications, and is growing in size and quality.

PMID- 22477774
TI  - The MORPHEUS protein crystallization screen.
AB  - A 96-condition initial screen for protein crystallization, called MORPHEUS, has
      been developed at the MRC Laboratory of Molecular Biology, Cambridge, England
      (MRC-LMB). The concept integrates several innovative approaches, such as
      chemically compatible mixes of potential ligands, new buffer systems and
      precipitant mixes that also act as cryoprotectants. Instead of gathering a set of
      crystallization conditions that have already been successful, a selection of
      molecules frequently observed in the Protein Data Bank (PDB) to co-crystallize
      with proteins has been made. These have been put together in mixes of similar
      chemical behaviour and structure, and combined with buffers and precipitant mixes
      that were also derived from PDB searches, to build the screen de novo.
      Observations made at the MRC-LMB and many practical aspects were also taken into
      account when formulating the screen. The resulting screen is easy to use,
      comprehensive yet small, and has already yielded a list of crystallization hits
      using both known and novel samples. As an indicator of success, the screen has
      now become one of the standard screens used routinely at the MRC-LMB when
      searching initial crystallization conditions for biological macromolecules.

PMID- 22477775
TI  - Development of a shutterless continuous rotation method using an X-ray CMOS
      detector for protein crystallography.
AB  - A new shutterless continuous rotation method using an X-ray complementary metal
      oxide semiconductor (CMOS) detector has been developed for high-speed, precise
      data collection in protein crystallography. The principle of operation and the
      basic performance of the X-ray CMOS detector (Hamamatsu Photonics KK C10158DK)
      have been shown to be appropriate to the shutterless continuous rotation method.
      The data quality of the continuous rotation method is comparable to that of the
      conventional oscillation method using a CCD detector and, furthermore, the
      combination with fine phi slicing improves the data accuracy without increasing
      the data-collection time. The new method is more sensitive to diffraction
      intensity because of the narrow dynamic range of the CMOS detector. However, the
      strong diffraction spots were found to be precisely measured by recording them on
      successive multiple images by selecting an adequate rotation step. The new method
      has been used to successfully determine three protein structures by multi- and
      single-wavelength anomalous diffraction phasing and has thereby been proved
      applicable in protein crystallography. The apparatus and method may become a
      powerful tool at synchrotron protein crystallography beamlines with important
      potential across a wide range of X-ray wavelengths.

PMID- 22477776
TI  - WebCSD: the online portal to the Cambridge Structural Database.
AB  - WebCSD, a new web-based application developed by the Cambridge Crystallographic
      Data Centre, offers fast searching of the Cambridge Structural Database using
      only a standard internet browser. Search facilities include two-dimensional
      substructure, molecular similarity, text/numeric and reduced cell searching.
      Text, chemical diagrams and three-dimensional structural information can all be
      studied in the results browser using the efficient entry summaries and embedded
      three-dimensional viewer.

PMID- 22477777
TI  - Morphology of polysorbate 80 (Tween 80) micelles in aqueous dimethyl sulfoxide
      solutions.
AB  - The structures of micelles of the surfactant polysorbate 80 (Tween 80) in 0-50%
      aqueous dimethyl sulfoxide (DMSO) solutions (pH 7.2, ionic strength 2.44 mM) were
      investigated by means of small-angle X-ray scattering. At DMSO concentrations of
      0-20%, core-shell cylinder micelles formed, and at 30-50% DMSO, core-shell discus
      micelles formed, that is, changing the hydrophobicity of the DMSO solvent mixture
      changed the micelles from core-shell cylinder micelles to core-shell discus
      micelles.

PMID- 22477779
TI  - A general method to determine twinning elements.
AB  - The fundamental theory of crystal twinning has been long established, leading to
      a significant advance in understanding the nature of this physical phenomenon.
      However, there remains a substantial gap between the elaborate theory and the
      practical determination of twinning elements. This paper proposes a direct and
      simple method - valid for any crystal structure and based on the minimum shear
      criterion - to calculate various twinning elements from the experimentally
      determined twinning plane for Type I twins or the twinning direction for Type II
      twins. Without additional efforts, it is generally applicable to identify and
      predict possible twinning modes occurring in a variety of crystalline solids.
      Therefore, the present method is a promising tool to characterize twinning
      elements, especially for those materials with complex crystal structure.

PMID- 22477778
TI  - Nanovolume optimization of protein crystal growth using the microcapillary
      protein crystallization system.
AB  - The Microcapillary Protein Crystallization System (MPCS) is a microfluidic, plug
      based crystallization technology that generates X-ray diffraction-ready protein
      crystals in nanolitre volumes. In this study, 28 out of 29 (93%) proteins
      crystallized by traditional vapor diffusion experiments were successfully
      crystallized by chemical gradient optimization experiments using the MPCS
      technology. In total, 90 out of 120 (75%) protein/precipitant combinations
      leading to initial crystal hits from vapor diffusion experiments were
      successfully crystallized using MPCS technology. Many of the resulting crystals
      produced high-quality X-ray diffraction data, and six novel protein structures
      that were derived from crystals harvested from MPCS CrystalCards are reported.

PMID- 22477780
TI  - Versatile in situ powder X-ray diffraction cells for solid-gas investigations.
AB  - This paper describes new sample cells and techniques for in situ powder X-ray
      diffraction specifically designed for gas absorption studies up to ca 300 bar (1
      bar = 100 000 Pa) gas pressure. The cells are for multipurpose use, in particular
      the study of solid-gas reactions in dosing or flow mode, but can also handle
      samples involved in solid-liquid-gas studies. The sample can be loaded into a
      single-crystal sapphire (Al(2)O(3)) capillary, or a quartz (SiO(2)) capillary
      closed at one end. The advantages of a sapphire single-crystal cell with regard
      to rapid pressure cycling are discussed, and burst pressures are calculated and
      measured to be ~300 bar. An alternative and simpler cell based on a thin-walled
      silicate or quartz glass capillary, connected to a gas source via a VCR fitting,
      enables studies up to ~100 bar. Advantages of the two cell types are compared and
      their applications are illustrated by case studies.

PMID- 22477781
TI  - Diffraction study of protein crystals grown in cryoloops and micromounts.
AB  - Protein crystals are usually grown in hanging or sitting drops and generally get
      transferred to a loop or micromount for cryocooling and data collection. This
      paper describes a method for growing crystals on cryoloops for easier
      manipulation of the crystals for data collection. This study also investigates
      the steps for the automation of this process and describes the design of a new
      tray for the method. The diffraction patterns and the structures of three
      proteins grown by both the new method and the conventional hanging-drop method
      are compared. The new setup is optimized for the automation of the crystal
      mounting process. Researchers could prepare nanolitre drops under ordinary
      laboratory conditions by growing the crystals directly in loops or micromounts.
      As has been pointed out before, higher levels of supersaturation can be obtained
      in very small volumes, and the new method may help in the exploration of
      additional crystallization conditions.

PMID- 22477782
TI  - Evaluation of the Bruker SMART X2S: crystallography for the nonspecialist?
AB  - An evaluation of the Bruker SMART X2S for the collection of crystallographic
      diffraction data, structure solution and refinement is carried out with a variety
      of materials with different electron densities, presenting some of the successes
      and challenges of automation in chemical crystallography.

PMID- 22477783
TI  - MoleCoolQt - a molecule viewer for charge-density research.
AB  - MoleCoolQt is a molecule viewer for charge-density research. Features include the
      visualization of local atomic coordinate systems in multipole refinements based
      on the Hansen and Coppens formalism as implemented, for example, in the XD suite.
      Residual peaks and holes from XDfft are translated so that they appear close to
      the nearest atom of the asymmetric unit. Critical points from a topological
      analysis of the charge density can also be visualized. As in the program MolIso,
      color-mapped isosurfaces can be generated with a simple interface. Apart from its
      visualization features the program interactively helps in assigning local atomic
      coordinate systems and local symmetry, which can be automatically detected and
      altered. Dummy atoms - as sometimes required for local atomic coordinate systems 
      are calculated on demand; XD system files are updated after changes. When using
      the invariom database, potential scattering factor assignment problems can be
      resolved by the use of an interactive dialog. The following file formats are
      supported: XD, MoPro, SHELX, GAUSSIAN (com, FChk, cube), CIF and PDB. MoleCoolQt
      is written in C++ using the Qt4 library, has a user-friendly graphical user
      interface, and is available for several flavors of Linux, Windows and MacOS.

PMID- 22477784
TI  - New software for statistical analysis of Cambridge Structural Database data.
AB  - A collection of new software tools is presented for the analysis of geometrical,
      chemical and crystallographic data from the Cambridge Structural Database (CSD).
      This software supersedes the program Vista. The new functionality is integrated
      into the program Mercury in order to provide statistical, charting and plotting
      options alongside three-dimensional structural visualization and analysis. The
      integration also permits immediate access to other information about specific CSD
      entries through the Mercury framework, a common requirement in CSD data analyses.
      In addition, the new software includes a range of more advanced features focused
      towards structural analysis such as principal components analysis, cone-angle
      correction in hydrogen-bond analyses and the ability to deal with topological
      symmetry that may be exhibited in molecular search fragments.

PMID- 22477785
TI  - ShelXle: a Qt graphical user interface for SHELXL.
AB  - ShelXle is a graphical user interface for SHELXL [Sheldrick, G. M. (2008). Acta
      Cryst. A64, 112-122], currently the most widely used program for small-molecule
      structure refinement. It combines an editor with syntax highlighting for the
      SHELXL-associated .ins (input) and .res (output) files with an interactive
      graphical display for visualization of a three-dimensional structure including
      the electron density (F(o)) and difference density (F(o)-F(c)) maps. Special
      features of ShelXle include intuitive atom (re-)naming, a strongly coupled
      editor, structure visualization in various mono and stereo modes, and a novel way
      of displaying disorder extending over special positions. ShelXle is completely
      compatible with all features of SHELXL and is written entirely in C++ using the
      Qt4 and FFTW libraries. It is available at no cost for Windows, Linux and Mac-OS
      X and as source code.

PMID- 22477786
TI  - ANODE: anomalous and heavy-atom density calculation.
AB  - The new program ANODE estimates anomalous or heavy-atom density by reversing the
      usual procedure for experimental phase determination by methods such as single-
      and multiple-wavelength anomalous diffraction and single isomorphous replacement
      anomalous scattering. Instead of adding a phase shift to the heavy-atom phases to
      obtain a starting value for the native protein phase, this phase shift is
      subtracted from the native phase to obtain the heavy-atom substructure phase. The
      required native phase is calculated from the information in a Protein Data Bank
      file of the structure. The resulting density enables even very weak anomalous
      scatterers such as sulfur to be located. Potential applications include the
      identification of unknown atoms and the validation of molecular replacement
      solutions.

PMID- 22477787
TI  - Dexmedetomidine: Are There Going to be Issues with Prolonged Administration?

PMID- 22477788
TI  - The dawn of pediatric personalized therapeutics.

PMID- 22477789
TI  - Dexmedetomidine use in pediatric intensive care and procedural sedation.
AB  - OBJECTIVE: Dexmedetomidine was approved by the Food and Drug Administration in
      1999 for the sedation of adults receiving mechanical ventilation in an intensive
      care setting. It provides sedation with minimal effects on respiratory function
      and may be used prior to, during, and following extubation. Based on its efficacy
      in adults, dexmedetomidine is now being explored as an alternative or adjunct to
      benzodiazepines and opioids in the pediatric intensive care setting. This review
      describes the studies evaluating the safety and efficacy dexmedetomidine in
      infants and children and provides recommendations on dosing and monitoring.
      METHODS: The MEDLINE (1950-November 2009) database was searched for pertinent
      abstracts, using the key term dexmedetomidine. Additional references were
      obtained from the bibliographies of the articles reviewed and the manufacturer.
      All available English-language case reports, clinical trials, retrospective
      studies, and review articles were evaluated. RESULTS: Over two dozen case series
      and clinical studies have documented the utility of dexmedetomidine as a sedative
      in children requiring mechanical ventilation or procedural sedation. In several
      papers, dexmedetomidine use resulted in a reduction in the dose or
      discontinuation of other sedative agents. It may be of particular benefit in
      children with neurologic impairment or in those who do not tolerate
      benzodiazepines. The most frequent adverse effects reported with dexmedetomidine
      have been hypotension and bradycardia, in 10% to 20% of patients. These effects
      typically resolve with dose reduction. CONCLUSIONS: Dexmedetomidine offers an
      additional choice for the sedation of children receiving mechanical ventilation
      in the intensive care setting or requiring procedural sedation. While
      dexmedetomidine is well tolerated when used at recommended doses, it has the
      potential to cause hypotension and bradycardia and requires close monitoring. In
      addition to clinical trials currently underway, larger controlled studies are
      needed to further define the role of dexmedetomidine in pediatric intensive care.

PMID- 22477790
TI  - Evaluation of adverse events noted in children receiving continuous infusions of
      dexmedetomidine in the intensive care unit.
AB  - OBJECTIVES: Dexmedetomidine is an alpha(2)-adrenergic receptor agonist with
      sedative and analgesic effects in mechanically ventilated adults and children.
      Safety and efficacy data are limited in children. The purpose of this study is to
      retrospectively identify the incidence and types of adverse events noted in
      children receiving continuous infusions of dexmedetomidine and evaluate potential
      risk factors for adverse events. METHODS: Between July 1, 2006, and July 31,
      2007, data were collected on all children (< 18 years) who received continuous
      infusions of dexmedetomidine. Data collection included demographics,
      dexmedetomidine regimen, and type/number of adverse events. The primary endpoint
      was the total number of adverse events noted, including: transient hypertension,
      hypotension, neurological manifestations, apnea, and bradycardia. Secondary
      endpoints included categorization of each type of adverse event and an assessment
      of risk factors. A logistic regression model was used to assess the relationship
      of adverse events with independent variables including length of ICU stay,
      cumulative dose, peak infusion rate, duration of therapy, PRISM III score, and
      bolus dose. RESULTS: Thirty-six patients received dexmedetomidine representing 41
      infusions. The median age was 16 months (range, 0.1-204 months) and median PRISM
      III score was 2 (range, 0-18). Eighteen (43.9%) patients received a bolus dose of
      dexmedetomidine. The median cumulative dose (mcg/kg) and peak dose (mcg/kg/hr)
      were 8.5 (range, 2.2-193.7) and 0.5 (range, 0.2-0.7), respectively.
      Dexmedetomidine was continued for a median of 20 (range, 3-263) hours. Six
      (14.6%) patients were slowly tapered off the continuous infusions. Twenty-one
      adverse events were noted in 17 patients, including 4 neurologic manifestations.
      Fourteen patients required interventions for adverse events. ICU length of stay
      was the only independent risk factor (p=0.036) for development of adverse events.
      CONCLUSIONS: Several potential adverse events were noted with dexmedetomidine
      continuous infusions including possible neurological manifestations. Further
      studies are needed looking at adverse events associated with dexmedetomidine use
      in the pediatric population.

PMID- 22477791
TI  - Neurologic withdrawal symptoms following abrupt discontinuation of a prolonged
      dexmedetomidine infusion in a child.
AB  - Dexmedetomidine is a alpha(2)-adrenergic agonist which possesses sedative,
      analgesic, and anxiolytic properties. It is approved for short-term use in adults
      to provide sedation while mechanically ventilated and for noninvasive procedural
      sedation. An increased number of anecdotal reports describe the use
      dexmedetomidine in children. Cardiovascular withdrawal symptoms have been
      reported in the literature. However, there have been few published reports of
      neurologic withdrawal symptoms following discontinuation of prolonged infusions
      of dexmedetomidine. We describe a 2 year-old child who received a prolonged
      continuous infusion (263 hours) of dexmedetomidine as an adjunctive sedative
      agent. Following abrupt discontinuation of dexmedetomidine, the patient presented
      with symptoms suggestive of neurological withdrawal. The symptoms gradually
      resolved over two days without further intervention, and the patient had full
      resolution of symptoms and was discharged home with no further neurologic
      sequelae.

PMID- 22477792
TI  - Dexmedetomidine to control agitation and delirium from toxic ingestions in
      adolescents.
AB  - Dexmedetomidine is an alpha(2)-adrenergic agonist that is approved by the Food
      and Drug Administration for the provision of short term (less than 24 hours)
      sedation of adults during mechanical ventilation. Given its beneficial
      physiologic effects including sedation and anxiolysis, various applications have
      been reported in the pediatric-aged patient. We report the use of dexmedetomidine
      to control the agitation and violent behavior which resulted from the ingestion
      of illicit drugs in 3 adolescents. The utility of dexmedetomidine in these
      scenarios is discussed and its potential beneficial effects on cardiovascular and
      respiratory function are reviewed.

PMID- 22477793
TI  - Continuous infusion of nafcillin for sternal osteomyelitis in an infant after
      cardiac surgery.
AB  - We report the use of the continuous infusion of nafcillin for the treatment of an
      infant who had methicillinsusceptible Staphylococcus aureus sternal osteomyelitis
      not responsive to traditional nafcillin dosing. The patient was successfully
      treated with surgical debridement and the continuous infusion of nafcillin. To
      our knowledge, this is the first report describing the successful use of the
      continuous infusion of nafcillin to treat an infant who had sternal osteomyelitis
      after cardiac surgery.

PMID- 22477794
TI  - Pediatric news.

PMID- 22477795
TI  - Switching of antiepileptic drug formulations.

PMID- 22477796
TI  - A Patient's Voice.

PMID- 22477797
TI  - Interplay between pediatric pharmacy practice and research to influence patient
      care.

PMID- 22477798
TI  - The History of PPAG: The First 30 Years.
AB  - This article describes the history of the Pediatric Pharmacy Advocacy Group
      (PPAG). From its humble beginning in 1979, to its formation as the Pediatric
      Directors of Pediatric Hospitals in 1985, through its time as the Pediatric
      Pharmacy Administrative Group and through its evolution into the PPAG. The
      organization was established and continues to be dedicated to improving
      medication therapy use in children. Its sole purpose is to promote safe and
      effective medication use in children through communication, education, and
      research. After three decades, PPAG has established itself as the preeminent
      pediatric pharmacy organization. Its annual conference has grown over the years
      to become the best educational and networking meeting for pediatric pharmacists
      worldwide.

PMID- 22477799
TI  - The Controversy over Generic Antiepileptic Drugs.
AB  - As patent protection ends for the next generation of antiepileptic drugs (AEDs),
      a complex debate continues over generic substitution of AEDs. On one hand,
      generic drug formulations provide cost savings for patients and society. On the
      other hand, patients with epilepsy and physicians are wary about the adequacy and
      efficacy of the Food and Drug Administration's (FDA) standards for generics. This
      article reviews current and proposed bioequivalence test procedures, summarizes
      new generic AED formulations and their costs, and discusses potential pitfalls in
      the current standards. These shortcomings include certain pharmacokinetic factors
      and clinical pharmacologic factors that may affect bioequivalence of generic
      AEDs, and statistical limitations of the standards. While the drug concentration
      differences between the brand name drug and each generic formulation are unlikely
      to be substantial, the differences with generic-to-generic switches will be
      greater and potentially clinically significant. Conversely, owing to their more
      favorable pharmacokinetic profile, newer AEDs may be less prone to problems with
      generic substitution than older ones. Unfortunately, very few data are available
      to guide decisions regarding what is best for an individual patient. Based on new
      prediction methods, generic substitution should be safe for many patients but
      identifying them ultimately requires more rigorous study.

PMID- 22477800
TI  - Pharmacokinetics and drug dosing in obese children.
AB  - OBJECTIVES: To review pharmacokinetics in obese children and to provide
      medication dosing recommendations. METHODS: EMBASE, MEDLINE, AND INTERNATIONAL
      PHARMACEUTICAL ABSTRACTS DATABASES WERE SEARCHED USING THE FOLLOWING TERMS:
      obesity, morbid obesity, overweight, pharmacokinetics, drug, dose, kidney
      function test, creatinine, pediatric, and child. RESULTS: We identified 10
      studies in which the authors examined drug dosing or pharmacokinetics for obese
      children. No information was found for drug absorption or metabolism. Obese
      children have a higher percent fat mass and a lower percent lean mass compared
      with normal-weight children. Therefore, in obese children, the volume of
      distribution of lipophilic drugs is most likely higher, and that of hydrophilic
      drugs is most likely lower, than in normal-weight children. Serum creatinine
      concentrations are higher in obese than normal-weight children. Total body weight
      is an appropriate size descriptor for calculating doses of antineoplastics,
      cefazolin, and succinylcholine in obese children. Initial tobramycin doses may be
      determined using an adjusted body weight, although using total body weight in the
      context of monitoring serum tobramycin concentrations would also be an
      appropriate strategy. We found no information for any of the opioids; antibiotics
      such as penicillins, carbapenems, vancomycin, and linezolid; antifungals; cardiac
      drugs such as digoxin and amiodarone; corticosteroids; benzodiazepines; and
      anticonvulsants. In particular, we found no information about medications that
      are widely distributed to adipose tissue or that can accumulate there.
      CONCLUSIONS: The available data are limited because of the small numbers of
      participating children, study design, or both. The number and type of drugs that
      have been studied limit our understanding of the pharmacokinetics in obese
      children. In the absence of dosing information for obese children, it is
      important to consider the nature and severity of a child's illness,
      comorbidities, organ function, and side effects and physiochemical properties of
      the drug. Extrapolating from available adult data is possible, as long as
      practitioners consider the effects of growth and development on the
      pharmacokinetics relevant to the child's age.

PMID- 22477801
TI  - Plasma amino Acid concentrations in 108 children receiving a pediatric amino Acid
      formulation as part of parenteral nutrition.
AB  - BACKGROUND: Plasma amino acid (PAA) levels can be largely normalized during
      parenteral nutrition (PN) in infants and children using a pediatric-specific
      amino acid (AA) formulation. However, these previous results were based on
      individual clinical studies of small populations of neonates and infants.
      OBJECTIVE: We have now examined AA levels in 108 children (0-7 years of age)
      receiving a pediatric-specific AA formulation in PN using a single analytical
      methodology. METHODS: Infants and children were enrolled in specific protocols
      and parents/caregivers gave informed consent. Patients were stable and receiving
      age-appropriate intakes of AA and non-protein calories. Samples were obtained
      between 8 and10 am, processed immediately, deproteinized, and AA concentrations
      (MUmol/L) were determined on a Beckman 6300 analyzer. Means and SD were
      calculated for sub-populations stratified by age: 0-1 month (48 patients, n=139),
      1-6 months (36 patients, n=124), 7-12 months (11 patients, n=41), and 1-7 years
      (13 patients, n=51). Z scores were calculated for each amino acid [(observed mean
      - normal control mean)/normal control SD]. RESULTS: When compared to the neonatal
      reference range, nonessential AA had Z scores that ranged from -1.84 (asparagine)
      to +1.48 (threonine). Only plasma free cystine, free tyrosine, and phenylalanine
      had Z scores outside the -2.0 to +2.0 range (95% confidence limits). Plasma free
      cystine values were low in all groups except neonates. Free tyrosine levels were
      low in all groups despite the presence of N-acetyl-L-tyrosine in the pediatric AA
      formulation. Phenylalanine levels were elevated only in neonates. When children 1
      to 7 years old were compared with an age-matched reference range, plasma free
      cystine values were low (Z score -2.47), as were plasma glutamine values (-3.11),
      but elevations were found in the dicarboxylic amino acids aspartic acid (+2.5)
      and glutamic acid (+4.27). Regardless of reference range used for comparison, all
      essential amino acids, except phenylalanine in neonates, were within range (-2 to
      +2 of the 95% confidence limits). CONCLUSIONS: While most AAs were within the
      normal range, formulation modifications are needed to normalize free cystine in
      infants and young children, free tyrosine in all children, and phenylalanine in
      neonates. The decrease in glutamine concentrations in older children has been
      noted by our group before, and may imply limited ability to convert glutamic acid
      to glutamine, or increased consumption of glutamine. In either case, increased
      concentrations of glutamine in older children, especially those receiving home
      parenteral nutrition, should be considered.

PMID- 22477802
TI  - Effects of age and weight-based dosing of enoxaparin on anti-factor xa levels in
      pediatric patients.
AB  - OBJECTIVE: The objective of this dose range study is to expand on the
      relationship between age and weight-based doses of enoxaparin and resulting
      levels of anti-factor Xa (anti-Xa) in pediatric patients. The primary outcome of
      this study is to determine the average dose of enoxaparin required to produce a
      therapeutic effect. Secondary outcomes include the number of enoxaparin dose
      changes required to achieve a therapeutic level of anti-Xa in each age group, the
      success rates of achieving and maintaining therapeutic anti-Xa levels, and the
      effect of serum antithrombin concentrations on anti-Xa levels. The study will
      also determine whether different dispensed concentrations of enoxaparin play a
      role in achieving therapeutic levels of anti-Xa. METHODS: Single center,
      retrospective chart review. Patients were excluded from the study if they were
      older than 18 years of age, were receiving enoxaparin for prophylactic purposes,
      had a creatinine clearance < 30 ml/min/1.73m(2), and if no anti-factor Xa levels
      were drawn. RESULTS: Average enoxaparin doses required for therapeutic levels of
      anti-factor Xa were 1.8 mg/kg for patients <1 month, 1.64 mg/kg (1 month to 1
      year), 1.45 mg/kg (1 to 6 years), and 1.05 mg/kg (>6 years of age). An average of
      3.24 dose changes was required for neonates to achieve therapeutic levels anti
      factor Xa. The success rates for achieving and maintaining therapeutic levels
      were both 41%. Patients with low serum antithrombin levels were more likely to
      have low anti-Xa levels than those with normal or high values, 52% vs 40% vs 18%,
      respectively. Patients receiving diluted concentrations, 10 or 20 mg/mL,
      experienced lower anti-Xa levels than patients who received the standard
      manufactured concentration of 100 mg/mL, 61% vs 33%. CONCLUSION: Based on this
      dose-range study, enoxaparin should be initiated at larger doses than recommended
      by the current guidelines to promptly achieve therapeutic anti-Xa levels. Doses
      should be divided into three age groups instead of two as currently suggested in
      the guidelines. To increase the likelihood of achieving therapeutic levels, the
      commercially available enoxaparin product should not be diluted if possible.

PMID- 22477803
TI  - Pharmacists' attitudes towards pediatric cough and cold products and behind the
      counter status.
AB  - BACKGROUND: Safety and efficacy issues regarding over-the-counter cough and cold
      (CAC) products for use in children have surfaced. Late in 2007 the FDA began
      reviewing CAC product status for use in children under 6 years old. OBJECTIVE: In
      regards to CAC products for children < 6 years old, to determine pharmacists: 1)
      comfort level in recommending; 2) attitudes towards behind-the-counter (BTC)
      status; and 3) level of support for BTC status. An additional objective was to
      determine how frequently pharmacists were asked for CAC product recommendations
      for children METHODS: Georgia Pharmacy Association members (2,045) were invited
      to anonymously participate in a self-administered online survey from January 3 -
      Feb 6, 2008. Topic areas included demographics, comfort in recommending CAC, and
      BTC status. RESULTS: Most responding pharmacists (99.1%) feel pediatric CAC
      medicine safety problems are due to inappropriate use. More than 50% of chain and
      independent pharmacists were asked to recommend CAC medicines for children during
      cold/flu season once a day or less, and 79% reported counseling on less than 50%
      of total CAC sales. The majority of pharmacists felt comfortable recommending CAC
      medications when thinking of both safety and efficacy. Most pharmacists supported
      a BTC condition of sale for children under two for decongestants, antihistamines,
      and antitussives, and for decongestants and antitussives for children between 2
      and 5 years old. CONCLUSIONS: Most pharmacists indicate comfort in recommending
      CAC despite lack of evidence for safety or efficacy and support BTC status.
      Pharmacist education on this topic would be useful.

PMID- 22477804
TI  - Stability of ziprasidone mesylate in an extemporaneously compounded oral
      solution.
AB  - OBJECTIVES: To formulate a liquid preparation of ziprasidone in a convenient
      concentration to allow dosing of less than 20 mg and of sufficient chemical and
      physical stability to enable an entire prescription or course of treatment to be
      prepared in a single batch. METHODS: Geodon for injection (ziprasidone mesylate),
      20 mg/mL, was diluted to 2.5 mg/mL in a commercially available sugar-free and
      alcohol-free, flavored syrup and stored at room temperature under ambient
      fluorescent light illumination, at room temperature in darkness, and under
      refrigeration. The ziprasidone content was measured in samples at various time
      intervals using a stability-indicating high-performance liquid chromatographic
      method. RESULTS: When refrigerated, the ziprasidone syrup that was compounded in
      a commercially available, sugar-free and alcohol-free vehicle maintained at least
      90% of stated potency for at least 6 weeks. Samples stored under other conditions
      were less stable, underscoring the manufacturer's labeling regarding refrigerated
      storage of the reconstituted injection. CONCLUSIONS: The findings suggest that
      chemical and physical stability are maintained for 2 weeks under refrigeration,
      allowing the convenience of compounding for the long-term needs of a particular
      patient, rather than daily compounding. The only storage condition we recommend
      is refrigeration at 5 degrees C.

PMID- 22477805
TI  - Opioid infusions in the neonatal intensive care unit.
AB  - OBJECTIVES: The primary objective of this study was to compare the use of opioid
      infusions to that proposed in guidelines published in an in-house medication
      handbook. Secondary objectives were to assess the documented use of a
      standardized neonatal pain assessment tool and to describe the supplemental use
      of opioids concurrent with an opioid infusion. METHODS: A retrospective chart
      review was performed for all patients in the NICU who received opioid infusions
      between November 1, 2005, and November 30, 2006. Data collected included patient
      characteristics, opioid infusion dosing and duration, supplemental opioid use,
      and pain assessment documentation. RESULTS: Of the110 neonates who received
      morphine or fentanyl during the study period, 65 patients met inclusion criteria.
      Reasons for starting an opioid infusion included nonsurgical sedation and/or
      analgesia (51%), postoperative pain (17%), and procedural pain (1%). No reason
      was documented for 31% of patients. Thirtyeight percent of neonates received a
      loading dose of opioid before initiation of the infusion. The median dose was 100
      mcg/kg (IQR=48.2) for morphine and and 1 mcg/kg (IQR=0.8) for fentanyl. The mean
      +/- SD starting rates of morphine and fentanyl infusions were 12.3 +/- 4.7
      mcg/kg/hr and 1.5 +/- 1.7 mcg/kg/hr, respectively. Supplemental opioid doses were
      given to 46% of neonates during the infusion period. Supplemental doses were
      given for procedures (69%) and pain/agitation/sedation (26%). No reason was
      documented for 5% of patients. The Neonatal Pain, Agitation and Sedation Scale
      scores were only documented 9% of the time for each day that the patient received
      an opioid infusion. CONCLUSIONS: Dosing of opioids generally was within the
      recommendations that are described in the in-house medication handbook. A
      substantial percentage of neonates received supplemental opioid doses while on
      opioid infusions, mostly for procedural pain management. Documentation of the
      reason for using opioid infusions and the assessment of neonatal pain was poor.

PMID- 22477806
TI  - Pediatric news.

PMID- 22477807
TI  - Penicillin prophylaxis in children with sickle cell disease.
AB  - Children who have sickle cell disease and are under the age of five years are at
      increased risk of life-threatening pneumococcal infection due to absent or non
      functional spleens and a decreased immune response. To prevent pneumococcal
      infection, the American Academy of Pediatrics recommends the use of penicillin
      prophylaxis in children with sickle cell disease under the age of five and in
      older children who have had a previous severe pneumococcal infection or have
      functional/surgical asplenia. These recommendations are based on two landmark
      studies, the first evaluating the effectiveness of penicillin prophylaxis and the
      second evaluating the duration of prophylaxis. Although the mortality rate from
      infection has been reduced following penicillin prophylaxis, altered immunologic
      response and penicillin-resistant S. pneumoniae remain a concern. This paper will
      review the literature that supports the use of penicillin prophylaxis, potential
      problems associated with prolonged therapy and recommendations for prophylaxis.

PMID- 22477808
TI  - Use of statins for dyslipidemia in the pediatric population.
AB  - Childhood dyslipidemia is on the rise and increasingly being recognized as an
      important risk factor for adult cardiovascular disease. Due to a heightened
      awareness surrounding this problem, the American Academy of Pediatrics published
      a clinical report concerning prevention, screening, diagnosis, and treatment of
      dyslipidemia in children. Of concern among practitioners is when to initiate
      pharmacologic therapy and which medications are safe and appropriate in children.
      The report addresses this concern by suggesting that pharmacologic management
      begin only in pediatric patients with substantially elevated LDL levels. Since
      statins are the drugs of choice among adult patients with elevated LDL levels, it
      would be appropriate to evaluate their outcome in pediatric patients. To evaluate
      the efficacy and safety of statins for the treatment of pediatric dyslipidemia, a
      comprehensive search was performed of the MEDLINE database and International
      Pharmaceutical Abstracts as well as references from additional review articles.
      The manufacturer was contacted for data regarding a newly approved statin.
      Fourteen trials were identified, eight of which were randomized, controlled
      trials involving greater than 50 patients with primary or familial
      hypercholesterolemia. Overall, the studies showed that statins are effective at
      lowering LDL levels (reduction from baseline: 17% to 50%) and are fairly well
      tolerated, with headache, gastrointestinal distress, and myalgia being the most
      common adverse effects. Statins were found to be an efficacious option for the
      management of familial hypercholesterolemia of childhood. However, concerns
      regarding long term safety and efficacy have not been established, and data in
      patients with secondary lipid disorders is lacking.

PMID- 22477809
TI  - Thimerosal-containing vaccines and autism: a review of recent epidemiologic
      studies.
AB  - Although epidemiologic evidence has not supported the hypothesis of a causal
      relationship between thimerosal-containing vaccines and autism, concerns continue
      about pediatric exposure to mercury through vaccine administration. A statement
      issued by the American Academy of Pediatrics and the US Public Health Service in
      1999 prompted the removal of thimerosal from many vaccines. In 2004, the
      Immunization Safety Review Committee of the Institute of Medicine rejected the
      hypothesis of a causal relationship between thimerosal-containing vaccines and
      autism.In a search of MEDLINE and EMBASE, we identified articles that address the
      potential association between thimerosal and neurodevelopmental disorders,
      specifically autism. In this article, we review recent pharmacokinetic and
      epidemiologic studies published between 2003 and 2008 regarding the proposed link
      between thimerosal and autism.

PMID- 22477810
TI  - Root cause analysis and subsequent intervention to improve first dose antibiotic
      turnaround time for hospitalized pediatric patients.
AB  - OBJECTIVE: Antibiotic timing is used as a quality standard for hospital
      accreditation and is an important quality measure. The study aim was to identify
      barriers in the process of first dose antibiotic administration on the pediatric
      floors at a tertiary healthcare center and carry out and test an intervention to
      improve turnaround time to less than one hour. METHODS: We conducted a quasi
      experimental pre-post study of hospitalized pediatric patients up to 18 years of
      age initiated on intravenous antibiotics. Every order for a first dose
      intravenous antibiotic was assessed on all pediatric floors (10/2008). Orders
      that did not meet the overall turnaround time goal of <= 1 hour were identified.
      A root cause analysis (RCA) was performed to identify reasons for delayed
      antibiotic administration. Barriers identified in the RCA were used to develop
      interventions (03/2009) to improve compliance, and the proportion of orders that
      met the goal was compared pre- (10/2008-02/2009) and post-intervention (04/2009
      05/2009). RESULTS: During the pre-intervention assessment period, 32 out of 46
      total physician orders for a first dose intravenous antibiotic did not meet the
      one-hour overall turnaround goal. A main reason for delay was failure to label
      antibiotic orders as first dose. We designed an intervention that included
      antibiotic audits and individualized feedback to prescribers. The mean +/- SD
      time from the written physician order to drug administration was 228 +/- 58
      minutes; timing improved to 55 +/- 4 minutes after the intervention. The
      proportion of antibiotics administered within one hour improved from 42.2% to 63%
      (p=0.0015). CONCLUSIONS: We identified system barriers associated with delayed
      antibiotic administration. Antibiotic timing was improved after continued
      surveillance and individualized feedback to providers.

PMID- 22477811
TI  - Computerized orders with standardized concentrations decrease dispensing errors
      of continuous infusion medications for pediatrics.
AB  - OBJECTIVES: The use of continuous infusion medications with individualized
      concentrations may increase the risk for errors in pediatric patients. The
      objective of this study was to evaluate the effect of computerized prescriber
      order entry (CPOE) for continuous infusions with standardized concentrations on
      frequency of pharmacy processing errors. In addition, time to process handwritten
      versus computerized infusion orders was evaluated and user satisfaction with CPOE
      as compared to handwritten orders was measured. METHODS: Using a crossover
      design, 10 pharmacists in the pediatric satellite within a university teaching
      hospital were given test scenarios of handwritten and CPOE order sheets and asked
      to process infusion orders using the pharmacy system in order to generate
      infusion labels. Participants were given three groups of orders: five correct
      handwritten orders, four handwritten orders written with deliberate errors, and
      five correct CPOE orders. Label errors were analyzed and time to complete the
      task was recorded. RESULTS: Using CPOE orders, participants required less
      processing time per infusion order (2 min, 5 sec +/- 58 sec) compared with time
      per infusion order in the first handwritten order sheet group (3 min, 7 sec +/- 1
      min, 20 sec) and the second handwritten order sheet group (3 min, 26 sec +/- 1
      min, 8 sec), (p<0.01). CPOE eliminated all error types except wrong
      concentration. With CPOE, 4% of infusions processed contained errors, compared
      with 26% of the first group of handwritten orders and 45% of the second group of
      handwritten orders (p<0.03). Pharmacists were more satisfied with CPOE orders
      when compared with the handwritten method (p=0.0001). CONCLUSIONS: CPOE orders
      saved pharmacists' time and greatly improved the safety of processing continuous
      infusions, although not all errors were eliminated. pharmacists were
      overwhelmingly satisfied with the CPOE orders.

PMID- 22477812
TI  - Once-daily amoxicillin for pharyngitis.
AB  - A once-daily antibiotic regimen for group A beta-hemolytic streptococcal
      pharyngitis (GABHS) could improve compliance and be effective in the prevention
      of rheumatic fever, a dangerous complication of untreated or poorly treated
      GABHS. Amoxicillin is ideal for once-daily dosing due to its low cost.
      Azithromycin, cefadroxil, ceftibuten, cefixime and extended release amoxicillin
      are also FDA approved to treat GABHS once daily; however, even when taken for
      short courses, these antibiotics are more expensive compared with a oncedaily
      dosing of conventional amoxicillin for 10 days. The American Heart Association
      recently recommended once-daily amoxicillin dosing when treating GABHS, and
      amoxicillin has been proven to be effective when dosed once daily, with no
      obvious disadvantage compared with twice-daily dosing or with conventional
      penicillin treatment 3 to 4 times daily.

PMID- 22477813
TI  - Smoking cessation treatment for adolescents.
AB  - Cigarette smoking in the adolescent population remains a public health concern. A
      significant portion of the adolescent population currently uses tobacco. Nicotine
      is particularly addicting in adolescents, and quitting is difficult. The goals
      for adolescent cigarette smoking efforts must include both primary prevention and
      smoking cessation. Bupropion and nicotine replacement therapies-including
      nicotine patches, gum, and nasal spray-have been studied to a limited extent in
      the adolescent population. Varenicline has not been evaluated as a treatment
      modality in adolescents. Long-term quit rates in the pharmacotherapy trials have
      not been optimal; however, decreases in cigarettes smoked per day have been
      observed. Several evidencebased guidelines include recommendations for smoking
      cessation in adolescents that include counseling and pharmacotherapy.
      Pharmacotherapy may be instituted for some adolescents in addition to counseling
      and behavioral interventions. Therapy should be individualized, based on smoking
      patterns, patient preferences, and concomitant disease states. Smoking cessation
      support for parents should be instituted as well. The pharmacist can play a large
      role in helping the adolescent quit smoking. Further studies evaluating
      pharmacotherapy options for smoking cessation in adolescents are necessary. If
      pharmacotherapy is used, it should be individualized and combined with
      psychosocial and behavioral interventions.

PMID- 22477814
TI  - Accuracy of empiric gentamicin dosing guidelines in neonates.
AB  - OBJECTIVE: To evaluate the accuracy of a neonatal gentamicin nomogram to achieve
      therapeutic gentamicin serum concentrations without further adjustment, allowing
      for decreased serum drug monitoring METHODS: Retrospective single center review
      of all gentamicin pharmacokinetic evaluations in patients <= 30 days of life from
      July 2005 - June 2007. Patients were evaluated for postnatal age, gestational
      age, weight, serum creatinine, dose/interval, serum drug peaks and troughs,
      results of discharge hearing test and recent use of indomethacin. Logistic
      regression was utilized to determine potential factors impacting overall dosing
      accuracy, potentially allowing for decreased therapeutic drug monitoring. Factors
      found to be significant were incorporated into new guidelines which were
      evaluated through pharmacokinetic modeling. RESULTS: Overall accuracy rate was
      84% when empiric dosing guidelines were utilized; 16% of all doses were changed
      due to supratherapeutic troughs and 1% were changed due to subtherapeutic peaks.
      Variables found to impact the necessity for dose changes incuded gestational age
      (p<=0.001), weight (p<=0.001), indomethacin use (p<=0.001), number of
      indomethacin doses used (p<=0.001 and p=0.009 for 1-3 and 4-6 doses,
      respectively), and SCr in patients >= 7 days old (p=0.028); however, only
      gestational age remained a significant predictor when all other factors were
      considered (p=0.008). The current guidelines were changed to account for
      increased troughs in patients <= 28 weeks gestation and examined through
      pharmacokinetic modeling. Pharmacokinetic modeling of the new guidelines
      predicted an overall accuracy of 94%. CONCLUSIONS: From the data gathered
      regarding the accuracy in patients >= 35 weeks gestation, we recommend to
      decrease therapeutic drug monitoring within this cohort. Utilizing the results of
      regression analysis, the current guidelines have been adjusted to allow for
      increased clearance in patients <= 28 weeks gestation, although they still need
      to be prospectively evaluated.

PMID- 22477815
TI  - Computerized pharmaceutical algorithm reduces medication administration errors
      during simulated resuscitations.
AB  - OBJECTIVE: Medication errors involving intravenous medications continue to be a
      significant problem, particularly in the pediatric population due to the high
      rate of point-of-care and weight-adjusted dosing. The pharmaceutical algorithm
      computerized calculator (pac2) assists in converting physician medication orders
      to correct volumes and rates of administration for intravenous medications. This
      study was designed to assess the efficacy of the pac2 in simulated clinical
      scenarios of point-of-care dosing. METHODS: The study design was a within-subject
      controlled study in which 33 nurses from pediatrics, pediatric critical care, or
      critical care (mean nursing experience of 10.9 years) carried out various point
      of-care medication-dosing scenarios with and without the aid of the pac2.
      RESULTS: Use of the pac2 resulted in a significantly higher percentage (mean [95%
      CI]) of medication volumes calculated and drawn accurately (91% [87-95%] versus
      61% [52-70%], p<0.0001), a higher percentage of correct recall of essential
      medication information (97% [95-99%] versus 45% [36-53%], p<0.0001), and better
      recognition of unsafe doses (93% [87-99%] versus 19% [12-27%], p<0.0001) as
      compared to usual practice. The pac2 also significantly reduced average
      medication calculation times (1.5 minutes [1.3-1.7 minutes] versus 1.9 minutes
      [1.6-2.2 minutes], p=0.0028) as compared to usual practice. CONCLUSIONS: The pac2
      significantly improved the performance of drug calculations by pediatric and
      critical care nurses during simulated clinical scenarios designed to mimic point
      of-care dosing. These results suggest that the pac2 addresses an area of safety
      vulnerability for point-of-care dosing practices and could be a useful addition
      to a hospital's overall program to minimize medication errors.

PMID- 22477816
TI  - Pilot comparison of three cardiopulmonary resuscitation medication dosing
      strategies in overweight children.
AB  - OBJECTIVES: Dose calculations using three variations of patient weight estimates
      (actual body weight [ABW], ideal body weight [IBW], and the Broselow Pediatric
      Emergency Tape [BPET, a length-based weight estimation tool]) were compared to
      administered doses of cardiopulmonary resuscitation medications in overweight and
      obese children to assess for differences in dose. METHODS: This retrospective
      cohort analysis included 54 consecutive pediatric patients who underwent
      emergency resuscitation at UMass Memorial Medical Center between January 2000 and
      October 2008. Patients were identified using ICD-9 codes related to
      cardiopulmonary resuscitation. Patients were included if they were overweight or
      obese, less than 12 years of age, less than 146 centimeters in length, and
      received emergency resuscitation medication(s). Doses of administered medications
      were recorded and compared to potential doses calculated based on ABW, IBW and
      the dose recommended by the BPET. Dose differences greater than 10% were
      considered clinically significant and dose differences greater than 20% were
      considered to be potential medication errors. RESULTS: Out of 54 possible
      patients, four overweight patients were included; none were obese. Ten total
      medication doses were assessed (minimum two per patient). In all patients, at
      least one comparator dose varied by greater than 20% from the administered dose.
      Four out of 10 doses calculated according to ABW, eight out of 10 doses
      calculated with IBW, and eight out of 10 doses recommended by the BPET all
      differed by greater than 20% from the administered dose. CONCLUSIONS: Dosing
      variations were observed when the dose received was compared to dosing using
      three variants of patient weight estimates. The largest dosing differences were
      observed upon comparison of the administered dose versus the dose recommended by
      the BPET.

PMID- 22477817
TI  - Angiotensin Converting Enzyme Inhibitor (ACEI)-Induced Acute Renal Failure in
      Premature Newborns with Congenital Heart Disease.
AB  - We report three cases of angiotensin converting enzyme inhibitor (ACEI) induced
      nephrotoxicity in preterm infants with congenital heart disease. Patients
      developed acute renal failure after starting captopril or enalapril at doses
      commonly prescribed for term neonates. There was no underlying renal disease
      found in these infants and the acute renal failure was reversible upon
      discontinuation of the ACEI. Conservative starting doses of ACEI should be used
      in patients with multiple risk factors for nephrotoxicity. A summary of
      previously reported ACEI induced renal failure in premature infants and
      congenital heart disease is included.

PMID- 22477818
TI  - The Use of Daptomycin and Linezolid to Treat Vancomycin-Intermediate
      Staphylococcus haemolyticus Infection in a Premature Infant.
AB  - Infections with staphylococcal species, especially coagulase-negative
      staphylococci are common after neurosurgical procedures. We report a case of a
      coagulase-negative staphylococci infection of a ventricular shunt site in a 105
      day-old, premature infant born at 25 weeks gestation with multiple medical
      problems. The patient was successfully treated with a combination of daptomycin
      and linezolid for the persistent infection, which was increasingly resistant to
      vancomycin. The patient was initially treated with a combination of vancomycin
      and rifampin; however, the course of therapy had to be changed when the bacteria
      was identified as having intermediate resistance to vancomycin. Therapy was
      initially changed to linezolid monotherapy, but culture results continued to be
      positive for the bacteria, necessitating removal of an external ventricular drain
      and combination therapy of daptomycin and linezolid for 2 weeks before insertion
      of a new ventricular shunt. The patient received 4 weeks of therapy with no
      further positive results of the culture analysis. To our knowledge, this is the
      first published case report of the use of daptomycin to successfully treat a
      central nervous system infection in a premature infant.

PMID- 22477819
TI  - Reversing the myths obstructing the determination of optimal age- and disease
      based drug dosing in pediatrics.
AB  - The need for critical, well-designed comprehensive clinical pharmacology research
      in pediatrics that encompasses the age continuum, from the most premature infant
      through adolescence, may be more important today than ever. New drug regimens
      often require greater adherence to specific dose guidelines to maximize efficacy
      and minimize toxic potential. The climate that allowed the propagation of the
      "therapeutic orphan" concept is now mostly of historical perspective.
      Nevertheless, the negative impact of this concept continues to linger due to
      continued propagation of many, now outdated myths surrounding the effective study
      of optimal drug dosing in pediatrics. Advances in clinical medicine combined with
      the advances in study design, sampling, and analysis has dramatically improved
      the paradigm for clinical pharmacology research in infants and children.
      Capitalizing upon and thoughtfully using these many advances while dispelling
      these myths will result in greater research focused on optimal drug therapy in
      pediatric practice.

PMID- 22477820
TI  - Nebulized furosemide in the treatment of bronchopulmonary dysplasia in preterm
      infants.
AB  - Bronchopulmonary dysplasia (BPD) is a chronic pulmonary disease commonly seen in
      preterm infants who require supplemental oxygen and/or assisted mechanical
      ventilation. BPD, a major cause of morbidity and mortality among premature
      infants, occurs in 5,000 to 10,000 premature infants in the United States each
      year. Despite numerous medical advances, no single intervention will prevent or
      treat BPD; hence, premature infants have an increased risk for developing
      significant sequelae that affect both cognitive and motor function. This article
      provides a brief overview of BPD and reviews the available literature regarding
      the safe and effective use of nebulized furosemide in the treatment of this
      disorder.

PMID- 22477821
TI  - Beyond Susceptible and Resistant, Part I: Treatment of Infections Due to Gram
      Negative Organisms With Inducible beta-Lactamases.
AB  - Inactivation of beta-lactams by the action of beta-lactamase enzymes is the most
      common mode of resistance to these drugs among Gram-negative organisms. The
      genomes of some key clinical pathogens such as Enterobacter and Pseudomonas
      encode AmpC, an inducible chromosomal beta-lactamase. The potent activity of AmpC
      against broad-spectrum beta-lactams complicates treatment of organisms with this
      gene. Antibiotic exposure can select for mutants expressing high levels of this
      enzyme, leading to the emergence of resistant isolates and failure of therapy,
      even when the initial isolate is fully susceptible. The risk of selecting for
      resistant organisms varies according to the particular beta-lactam used for
      treatment. This article reviews the microbiology of these enzymes, summarizes
      clinical data on the frequency emergence of resistance, and discusses
      considerations for antimicrobial treatment of these organisms.

PMID- 22477822
TI  - Omega-3 long chain polyunsaturated Fatty acids for treatment of parenteral
      nutrition-associated liver disease: a review of the literature.
AB  - Parenteral nutrition-associated liver disease (PNALD) is a complex disease that
      is diagnosed by clinical presentation, biochemical markers of liver injury,
      concurrent use of parenteral nutrition (PN), and negative workup for other causes
      of liver disease. For the past 30 years, clinicians have had few effective
      treatments for PNALD and when disease progressed to liver cirrhosis it was
      historically associated with poor outcomes. Within the past 5 years there has
      been some encouraging evidence for the potential benefits of fish oils, rich in
      omega-3 long-chain polyunsaturated fatty acids (omega3PUFA), in reversing liver
      injury associated with PN. This article reviews the current literature relating
      to omega3PUFA and PNALD.

PMID- 22477823
TI  - Dosing evaluation of continuous intravenous fentanyl infusions in overweight
      children: a pilot study.
AB  - OBJECTIVES: The purpose of this study was to assess the appropriateness of weight
      based dosing of continuous intravenous infusion of fentanyl in overweight/obese
      versus normal-weight children admitted to the pediatric intensive care unit
      (PICU). METHODS: This retrospective, pilot study included 5- to 12-year-old
      children admitted to the PICU over a 2-year period who received continuous
      intravenous infusion fentanyl for >= 4 days. The overweight/obese group included
      children with a body mass index (BMI) >= 85th percentile, while the control group
      included children with BMI < 85th percentile. The primary objective was to
      compare the number of fentanyl continuous intravenous infusion dosage changes
      required per day to achieve adequate sedation between groups. Secondarily, opioid
      withdrawal symptoms following the discontinuation of fentanyl and concomitant
      sedative/analgesic regimens were analyzed between groups. Student t tests and chi
      square analyses were performed as appropriate, with an a priori alpha of p<=0.05.
      RESULTS: Sixteen normal-weight and 15 overweight/obese patients with 18 and 16
      individual infusions were identified, respectively. No statistical difference was
      found between groups for the number of dosage changes per day, 0.92 versus 0.69
      (p=0.16). Five patients in each group experienced withdrawal (p=0.71). The total
      number of concomitant bolus doses received was greater in the overweight/obese
      group but did not reach statistical significance. CONCLUSIONS: There was a
      numerical, but statistically nonsignificant difference in the number of
      sedative/analgesic bolus doses and dosing changes per day between groups. Larger
      studies are warranted to determine the optimal dosing strategy for continuous
      intravenous infusion fentanyl in overweight/obese children.

PMID- 22477824
TI  - Pharmacists' perceived knowledge and expertise in selected pediatric topics.
AB  - OBJECTIVES: The purpose of this study is to determine pharmacists' perceived
      knowledge and expertise required to make recommendations regarding selected
      pediatric topics. METHODS: A questionnaire was distributed to 400 pharmacists
      practicing in community, hospital, and home care settings. This instrument
      explored their perceived knowledge, expertise, and comfort in providing
      recommendations related to 38 pediatric topics. The impact of responder
      demographics on differences in perceived knowledge and expertise for each topic
      were evaluated. RESULTS: Ninety-five of 400 (24%) questionnaires were returned
      completed or partially completed. Forty-seven and 36 of responders practiced in
      the community or inpatient hospital setting, respectively. Seventy percent of
      responders reported that <= 40% of their patients were children. In general,
      responders believed they had the knowledge and expertise to make recommendations
      for the frequently occurring conditions or topics but not for the less familiar.
      Formal pediatric training was the most influential responder characteristic with
      a larger proportion having training that they believed enables them to have
      knowledge and expertise to make recommendations. Although less impressive,
      experience of more than 5 years and a community-based practice were also
      important factors. CONCLUSION: Additional training is beneficial in increasing
      the perceived knowledge and comfort of pharmacists making recommendations
      regarding pediatric patients.

PMID- 22477825
TI  - Clevidipine for perioperative blood pressure control in infants and children
      undergoing cardiac surgery for congenital heart disease.
AB  - OBJECTIVE: To determine the efficacy and adverse effect profile of clevidipine
      when used for perioperative blood pressure (BP) control during surgery for
      congenital heart disease (CHD). METHODS: We retrospectively reviewed our
      experience with the perioperative use of clevidipine in pediatric-aged patients
      undergoing surgery for CHD. RESULTS: The study cohort included 14 patients
      ranging from 11 months to 15 years (7.4 +/- 4.6 years) and weighing from 5 to 41
      kg (21.8 +/- 11.1 kg). Clevidipine was administered as a continuous infusion for
      control of either postoperative BP or intraoperative mean arterial pressure (MAP)
      during cooling and cardiopulmonary bypass (CPB). It was administered as a bolus
      for BP control during emergence from anesthesia following cardiac surgery. The
      continuous infusion was started at 1 mcg/kg/min and increased in increments of
      0.5 to 1 mcg/kg/min as needed. For postoperative BP control, dosing requirements
      varied from 1 to 7 mcg/kg/min (mean = 2.0 +/- 1.2 mcg/kg/min). The target BP was
      achieved within 5 minutes in all patients. Two patients were treated with
      intravenous or oral propranolol for an increase in heart rate (HR) while
      receiving clevidipine. Despite doses up to 10 mcg/kg/min, effective control of
      MAP could not be achieved during CPB and cooling (core body temperature 28
      degrees C to 32 degrees C). Bolus doses of clevidipine (10 to 15 mcg/kg)
      controlled BP during emergence from anesthesia with a decrease of the MAP from 97
      +/- 6 mm Hg to 71 +/- 5 mm Hg (p<0.01). CONCLUSIONS: Clevidipine is effective for
      perioperative BP control in infants and children with CHD; however, it does not
      appear effective in controlling MAP during cooling and CPB.

PMID- 22477826
TI  - Carbamazepine-induced acute generalized exanthematous pustulosis: a case report.
AB  - A 15-year-old adolescent was admitted to the hospital for management of a
      generalized pruritic skin rash, which had appeared 10 days prior to admission.
      Carbamazepine (CBZ) and insulin were initiated 44 and 23 days prior to the onset
      of the skin rash (day 44), respectively. Clinical examination showed bluish
      lesions on the tongue and bilateral keratoconjunctivitis. His skin was very
      erythematous and pruritic without edema and covered with hundreds of
      nonfollicular pustules mainly on the trunk and skin folds. Laboratory assessment
      revealed leukocytosis, hypereosinophilia, and thrombocytopenia. A sample of
      superficial pus from a pustule on the trunk showed a significant number of
      leukocytes as well as a significant number of Staphylococcus aureus and
      Lancefield Group B beta-hemolytic streptococci strains. An abdominal skin biopsy
      revealed acute to subacute folliculocentric spongiotic dermatitis with subcorneal
      pustules. All of these observations were consistent with a diagnosis of acute
      generalized exanthematous pustulosis (AGEP). Although we could not exclude with
      certainty the role of insulin initiated on day 21 and discontinued on day 55 with
      substitution to oral metformin and repaglinide, no cases of AGEP have ever been
      published with insulin, and skin lesions were not related to injection sites.
      This article describes a probable case of CBZ-induced acute generalized
      exanthematous pustulosis in a 15-year-old adolescent.

PMID- 22477827
TI  - Pediatric news.

PMID- 22477828
TI  - Respiratory syncytial virus pathophysiology and affect of palivizumab in special
      populations: cystic fibrosis and immunosuppression.

PMID- 22477829
TI  - Respiratory Syncytial Virus Prophylaxis in Special Populations: Is it Something
      Worth Considering in Cystic Fibrosis and Immunosuppression?
AB  - Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of infant
      hospitalization in the United States. Prophylaxis with palivizumab is effective
      in reducing RSV hospitalizations in premature infants and in infants or children
      with chronic lung disease or congenital heart disease. Patients with CF or those
      who are immunocompromised may be at increased risk for RSV infection-related
      complications; hence, prophylaxis may prove beneficial to these populations. The
      extent of palivizumab use in the CF and immunocompromised populations is
      variable. Palivizumab appears to be safe and may be effective in infants and
      young children with CF and immunocompromise. However, well-designed, randomized,
      controlled trials published in peer-reviewed journals are lacking, and its
      routine use can therefore not be recommended at this time. If used in patients
      with CF or those who are immunocompromised, RSV prophylaxis should be restricted
      to peak outbreak months in order to optimize the cost benefit of palivizumab.

PMID- 22477830
TI  - Hyperphosphatemia in pediatric oncology patients receiving liposomal amphotericin
      B.
AB  - OBJECTIVE: After transitioning our front-line amphotericin product to the
      liposomal formulation, we observed an increased incidence of hyperphosphatemia.
      We aimed to determine the incidence of hyperphosphatemia in children with
      oncologic disorders receiving an amphotericin B product and to establish whether
      the incidence varies depending on amphotericin formulation. METHODS: This
      retrospective review of the medical record was conducted at a tertiary, free
      standing children's hospital. Pharmacy data revealed 159 patients receiving an
      amphotericin product between November 2006 and December 2008. Doses of
      amphotericin, serum phosphorous, calcium and creatinine concentrations were
      recorded at daily time points during the 10 days following both initiation and
      discontinuation of amphotericin. Administration of phosphate binders and total
      parenteral nutrition was noted. The incidence of hyperphosphatemia, defined as a
      serum value greater than the age-adjusted upper limit of normal, was compared
      among the amphotericin groups. RESULTS: One hundred thirty-nine amphotericin
      recipients had a serum phosphorus measurement during amphotericin therapy. Final
      analysis included 117 children, of which 64 (55%) were oncology patients.
      Deoxycholate (mean maximum dose 1 mg/kg), lipid complex (mean maximum dose 4.8
      mg/kg) and liposomal amphotericin (mean maximum dose 4.9 mg/kg) were used in 24
      (20.5%), 37 (31.6%) and 56 (47.9%) of all patients, respectively.
      Hyperphosphatemia developed in 27% (32/117) of all patients, and in 33% (21/64)
      of oncology patients. Similar to within all recipients, among oncology patients,
      45% (n=18) of liposomal recipients demonstrated hyperphosphatemia compared to 13%
      of those receiving lipid complex (n=3, p=0.007). No oncology patient received
      deoxycholate. CONCLUSION: Nearly 45% of children with oncologic disorders
      receiving liposomal amphotericin developed hyperphosphatemia. The incidence is
      significantly greater for the liposomal formulation than either of the other
      amphotericin formulations.

PMID- 22477831
TI  - Aluminum in pediatric parenteral nutrition products: measured versus labeled
      content.
AB  - OBJECTIVE: Aluminum is a contaminant in all parenteral nutrition solutions.
      Manufacturers currently label these products with the maximum aluminum content at
      the time of expiry, but there are no published data to establish the actual
      measured concentration of aluminum in parenteral nutrition solution products
      prior to being compounded in the clinical setting. This investigation assessed
      quantitative aluminum content of products commonly used in the formulation of
      parenteral nutrition solutions. The objective of this study is to determine the
      best products to be used when compounding parenteral nutrition solutions (i.e.,
      those with the least amount of aluminum contamination). METHODS: All products
      available in the United States from all manufacturers used in the production of
      parenteral nutrition solutions were identified and collected. Three lots were
      collected for each identified product. Samples were quantitatively analyzed by
      Mayo Laboratories. These measured concentrations were then compared to the
      manufacturers' labeled concentration. RESULTS: Large lot-to-lot and manufacturer
      to-manufacturer differences were noted for all products. Measured aluminum
      concentrations were less than manufacturer-labeled values for all products.
      CONCLUSIONS: The actual aluminum concentrations of all the parenteral nutrition
      solutions were significantly less than the aluminum content based on
      manufacturers' labels. These findings indicate that 1) the manufacturers should
      label their products with actual aluminum content at the time of product release
      rather than at the time of expiry, 2) that there are manufacturers whose products
      provide significantly less aluminum contamination than others, and 3) pharmacists
      can select products with the lowest amounts of aluminum contamination and reduce
      the aluminum exposure in their patients.

PMID- 22477832
TI  - Arthritis associated with antithyroid therapy in a 15-year-old girl.
AB  - A 15-year-old white girl with autoimmune thyroiditis developed arthritis 3 weeks
      after starting therapy with the antithyroid drug thiamazole. Because an adverse
      drug reaction of thionamide therapy was suspected, thiamazole was withdrawn, and
      symptoms disappeared rapidly. Thionamide therapy is indicated for hyperthyroidism
      and has been widely used since 1948. Reported adverse drug reactions range from
      mild to potentially life threatening. Arthritis is an uncommon but serious side
      effect and can develop as a part of the antithyroid arthritis syndrome or as a
      part of antineutrophil cytoplasmic antibody-associated vasculitis that is induced
      by antithyroid drugs. Little is known about the exact pathogenesis. Therapy
      consists of prompt discontinuation of the drug, where upon symptoms rapidly
      disappear. Because of possible cross-reactivity with alternative thionamides,
      another form of treatment for hyperthyroidism is recommended. Clinical awareness
      is important, and prompt withdrawal of the antithyroid drug is necessary when
      serious side effects occur.

PMID- 22477833
TI  - Use of intravesicular amikacin irrigations for the treatment and prophylaxis of
      urinary tract infections in a patient with spina bifida and neurogenic bladder: a
      case report.
AB  - This case report describes the use of intravesicular amikacin irrigations to
      treat and prevent urinary tract infections (UTIs) in a pediatric patient with
      spina bifida and neurogenic bladder. A 15 year old Hispanic female was admitted
      for a UTI caused by Enterobacter cloacae and multiple-drug resistant Pseudomonas
      aeruginosa. A 7 day course of daily intravenous amikacin and ceftazidime was
      initiated along with twice daily intravesicular amikacin irrigations (15 mg/30
      mL) with a dwell time of 2 hours. The patient improved and was discharged on
      prophylactic Bactrim SS (sulfamethoxazole/trimethoprim) 1 tablet daily and
      intravesicular amikacin irrigations (15 mg/30 mL) once every other day.
      Approximately 2 months after discharge, the patient developed another UTI from
      multidrug resistant Escherichia coli and was treated with a 14 day course of
      daily intravenous ciprofloxacin accompanied by daily intravesicular amikacin
      irrigations. Adjunctive therapy with either once daily or twice daily
      intravesicular amikacin irrigations successfully treated the patient's UTI.
      However, prophylactic treatment with intravesicular amikacin failed to prevent
      future UTIs in this patient.

PMID- 22477834
TI  - Bivalirudin use in an infant with persistent clotting on unfractionated heparin.
AB  - Bivalirudin is a direct thrombin inhibitor approved for use in adult patients
      with heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary
      intervention. Recently, its use in the pediatric population has increased due to
      its anti-thrombin-independent mechanism of action. As heparin products produce
      great inter- and intraindividual variability in pediatric patients, often due to
      decreased anti-thrombin concentrations in the first year of life, some
      practitioners have turned to direct thrombin inhibitors, such as bivalirudin, for
      more predictable pharmacokinetics and effects on bound and circulating thrombin.
      We report our experience using bivalirudin in a 2-month-old female with recurrent
      systemic thrombi despite continuous unfractionated heparin infusion. Due to the
      patient's inability to maintain therapeutic activated partial thromboplastin time
      (aPTT) values during heparin infusion, bivalirudin was initiated at 0.1 mg/kg/h
      and increased due to subtherapeutic aPTTs to a maximum of 0.58 mg/kg/h.
      Therapeutic aPTTs were achieved at the increased dose; however, the patient's
      worsening renal impairment with resultant drug accumulation and overwhelming
      sepsis on day 5 of therapy led to discontinuation of the infusion and the
      initiation of comfort measures.

PMID- 22477835
TI  - Dexmedetomidine as part of balanced anesthesia care in children with malignant
      hyperthermia risk and egg allergy.
AB  - Malignant hyperthermia is an acute hypermetabolic crisis triggered in susceptible
      patients by the administration of succinylcholine or a volatile anesthetic agent.
      When anesthesia care is provided to malignant hyperthermia-susceptible patients,
      a total intravenous anesthesia technique with propofol is frequently chosen.
      However, coexisting allergies to egg and soybeans may contraindicate the use of
      propofol. We present our experience with the use of dexmedetomidine as part of
      the anesthesia regimen in 3 patients with family histories of malignant
      hyperthermia and personal histories of egg or soybean allergies. In 2 patients,
      dexmedetomidine was used as part of a general anesthesia regimen and for sedation
      during spinal anesthesia in the third patient. Previous reports of the use of
      dexmedetomidine in patients susceptible to malignant hyperthermia are reviewed,
      and its benefits in such patients are discussed.

PMID- 22477836
TI  - The role of the pediatric pharmacist in personalized medicine and clinical
      pharmacogenomics for children: pediatric pharmacogenomics working group.
AB  - With the initiatives by the National Institutes of Health and the Food and Drug
      Administration, pharmacogenomics has now moved from the laboratory to the patient
      bedside. Over 100 drug-products now contain pharmacogenomic information as part
      of their labeling. Many of these are commonly used in the pediatric population.
      Direct-to-consumer genetic test kits also require intervention and guidance from
      healthcare professionals. This increased trend towards personalized medicine
      mandates that healthcare professionals develop a working knowledge about
      pharmacogenomics and its application towards patient care. Because
      pharmacogenomic testing can provide patient-specific predictors for response to
      and safety of medications, pharmacists are positioned to play an active role in
      pharmacogenomic testing, clinical interpretation of results, and recommendations
      for individualization of drug therapy. Opportunities for pharmacists exist in
      both inpatient and outpatient settings, such as pharmacist-managed clinical
      pharmacogenomics consultation services and educating patients and families about
      pharmacogenomic testing. In addition to clinical roles, pharmacists may also be
      involved in genetically-influenced drug discovery and development. Given the
      potential for genetic and age-dependent factors to influence drug selection and
      dosing, pediatric pharmacists should be involved in the development of dosing
      recommendations and interprofessional practice guidelines regarding
      pharmacogenomic testing in pediatric patients. Opportunities to become
      knowledgeable and competent in pharmacogenomics span from coursework as part of
      the pharmacy curriculum to postgraduate education (e.g., residencies,
      fellowships, continuing education). However, there exists a need for additional
      postgraduate learning opportunities for practicing pharmacists. As a result, the
      Pediatric Pharmacy Advocacy Group (PPAG) acknowledges a need for increased
      education of both student and practicing pharmacists, with consideration of
      special patient populations, such as infants and children. PPAG endorses and
      advocates for the involvement of pediatric pharmacists in pharmacogenomic testing
      and in using those results to provide safe and effective medication use in
      pediatric patients of all ages. Additionally, PPAG strongly encourages pediatric
      pharmacists to take responsibility for educating patients and their families
      about the importance of pharmacogenomic testing and its role in the safe and
      effective use of medications.

PMID- 22477837
TI  - Pediatric news.

PMID- 22477838
TI  - Mental health in family medicine: a new opportunity.

PMID- 22477839
TI  - Mental health and primary care: family medicine has a role.

PMID- 22477840
TI  - Integrating mental health into primary healthcare.

PMID- 22477841
TI  - What is primary care mental health?: WHO and Wonca Working Party on Mental
      Health.

PMID- 22477842
TI  - Does perceived financial strain predict depression among young women?
      Longitudinal findings from the Southampton Women's Survey.
AB  - Background Social and financial environment has an influence on the incidence of
      depression. We studied perceived financial strain as a risk factor for
      development of depression among a large cohort of young women in Southampton,
      UK.Methods We recruited a large number of young women in Southampton in the
      Southampton Women's Survey, a longitudinal study looking at factors influencing
      the health of women and their offspring. Women were asked to complete a baseline
      questionnaire, which included the GHQ-12 (an assessment of mental health), as
      well as questions on perceived financial strain and past history of depression.
      They were followed up two years later through their general practitioner (GP)
      records for evidence of incident mental illness.Results A total of 7020 women
      completed the baseline questionnaire including the GHQ-12. Of these, 5237 (74.6%)
      had records available for follow-up. Among those developing depression, there was
      a higher proportion receiving benefits, and a higher level of perceived financial
      strain. There were also modest elevations in perceived stress, and poorer levels
      of educational attainment. Among women not depressed at baseline, and with no
      previous history of depression, those in receipt of state benefits at baseline
      had a significantly elevated risk of developing the disorder - hazard ratio 1.61
      (95% confidence interval (CI) 1.13-2.3). The risk associated with perceived
      financial strain was 2.16 (95% CI 1.14-4.11), but this did not remain
      statistically significant after adjustment was made for receipt of benefits,
      educational qualification, and perceived stress.Conclusion Financial hardship as
      evidenced by receipt of benefits is a strong independent predictor for the
      development of depression. Although perception of financial strain is also a
      predictor for incident depression, the risk associated with this subjective
      characteristic does not remain significantly elevated after adjustment. Future
      studies of the aetiology of depression should incorporate ascertainment of actual
      financial status.

PMID- 22477843
TI  - Major depression and recent physical or sexual abuse increase readmissions among
      high-utilising primary care patients.
AB  - Objective To investigate whether current major depression and past
      physical/sexual victimisation is associated with recurrent general hospital
      admissions.Method Ninety-six inner-city primary care patients with a history of
      high medical service utilisation completed the PRIME-MD and the Abuse Assessment
      Screen; medical records were reviewed to assess reasons for re-hospitalisations.
      We compared hospitalisation rates over the preceding 12 months between those
      subjects with and without major depression and those with and without histories
      of abuse.Results Compared to non-abused subjects, patients with past-year abuse
      showed significantly increased past-year hospitalisations (3.2 versus 1.8, P =
      0.007). Re-admissions were related to chronic disease management and were not
      because of acute physical effects of trauma. Analysis of variance revealed that
      major depressive disorder and past-year abuse history interacted to increase an
      association with re-admissions.Conclusions Past-year abuse was independently
      associated with increased hospital admissions. Psychological effects of recent
      abuse combined with depression may particularly increase rates of
      medical/surgical hospitalisations.

PMID- 22477844
TI  - A controlled trial of internet-based cognitive-behavioural therapy for panic
      disorder with face-to-face support from a general practitioner or email support
      from a psychologist.
AB  - Background Panic disorder (PD) is one of the most common anxiety disorders seen
      in general practice, but provision of evidence-based cognitive-behavioural
      treatment (CBT) is rare. Many Australian GPs are now trained to deliver focused
      psychological strategies, but in practice this is time consuming and
      costly.Objective To evaluate the efficacy of an internet-based CBT intervention
      (Panic Online) for the treatment of PD supported by general practitioner (GP)
      delivered therapeutic assistance.Design Panic Online supported by GP-delivered
      face-to-face therapy was compared to Panic Online supported by psychologist
      delivered email therapy.Methods Sixty-five people with a primary diagnosis of PD
      (78% of whom also had agoraphobia) completed 12 weeks of therapy using Panic
      Online and therapeutic assistance with his/her GP (n = 34) or a clinical
      psychologist (n = 31). The mean duration of PD for participants allocated to
      these groups was 59 months and 58 months, respectively. Participants completed a
      clinical diagnostic interview delivered by a psychologist via telephone and
      questionnaires to assess panic-related symptoms, before and after
      treatment.Results The total attrition rate was 20%, with no group differences in
      attrition frequency. Both treatments led to significant improvements in panic
      attack frequency, depression, anxiety, stress, anxiety sensitivity and quality of
      life. There were no statistically significant differences in the two treatments
      on any of these measures, or in the frequency of participants with clinically
      significant PD at post assessment.Conclusions When provided with accessible
      online treatment protocols, GPs trained to deliver focused psychological
      strategies can achieve patient outcomes comparable to efficacious treatments
      delivered by clinical psychologists. The findings of this research provide a
      model for how GPs may be assisted to provide evidence-based mental healthcare
      successfully.

PMID- 22477845
TI  - All in for mental health: a pilot study of group therapy for people experiencing
      anxiety and/or depression and a significant other of their choice.
AB  - Background A need to provide treatment for people with anxiety and/or depression,
      and to provide preventive strategies for individuals who love them has been
      identified. In response, an innovative group therapy programme for people with
      anxiety and/or depression and a significant other of their choice was developed
      and implemented.Methods Mixed methods were employed. Five 'significant other'
      groups were held between May 2005 and June 2006. All group participants were
      requested to complete the Depression Anxiety Stress Scale (DASS), World Health
      Organization Quality of Life Assessment (WHOQol) and Connor-Davidson Resilience
      Scale (CD-RISC), pre- and post-therapy, and three months after their last therapy
      session. In addition, participants who attended groups between July and September
      2005 were invited to provide feedback about the group therapy in an individual
      semi-structured interview.Results Pilot results indicate positive responses from
      clients, related to facilitation of knowledge and understanding and skills
      development. For people referred to the group significant improvements were found
      in the DASS scores, resilience, psychological health and living
      environment.Limitations Due to the small sample size, and lack of follow-up data
      and control group, the findings need to be considered with caution and indicate
      the necessity to collect further data to provide conclusive findings.Conclusions
      Overall, the outcome of the 'significant other' pilot programme was useful, in
      that it facilitated a number of positive outcomes for participants. Areas for
      further research have been identified including strategies to improve social
      relationships, the de-identification with the sick/supporter role, and testing
      this model with diverse populations and clinical groups.

PMID- 22477846
TI  - Addressing long-term physical healthcare needs in a forensic mental health
      inpatient population using the UK primary care Quality and Outcomes Framework
      (QOF): an audit.
AB  - Objectives This audit aims to evaluate the effectiveness of delivering an
      equivalent primary care service to a long-term forensic psychiatric inpatient
      population, using the UK primary care national Quality and Outcomes Framework
      (QOF).Method The audit compares the targets met by the general practitioner with
      special interest (GPwSI) service, using local and national QOF benchmarks (2005
      2006), and determines the prevalence of chronic disease in a long-term inpatient
      forensic psychiatry population.Results The audit results show that the UK
      national QOF is a useful tool for assessment and evaluation of physical
      healthcare needs in a non-community based population. It shows an increased
      prevalence of all QOF-assessed long-term physical conditions when compared to the
      local East London population and national UK population, confirming previously
      reported elevated levels of physical healthcare need in psychiatric
      populations.Conclusions This audit shows that the UK General Practice QOF can be
      used as a standardised instrument for commissioning and monitoring the delivery
      of physical health services to in-patient psychiatric populations, and for the
      evaluation of the effectiveness of clinical interventions in long-term physical
      conditions. The audit also demonstrates the effectiveness of using a GPwSI in
      healthcare delivery in non-community based settings. We suggest that the findings
      may be generalisable to other long-term inpatient psychiatric and prison
      populations in order to further the objective of delivering an equivalent primary
      care service to all populations.The QOF is a set of national primary care audit
      standards and is freely available on the British Medical Association website or
      the UK Department of Health website. We suggest that primary care workers in
      health economies who have not yet developed their own national primary care
      standards can access and adapt these standards in order to improve the clinical
      standards of care given to the primary care populations that they serve.

PMID- 22477847
TI  - Mental health education resources for Australia's general practitioners.

PMID- 22477848
TI  - Wonca conferences and other meetings of interest at a glance.

PMID- 22477850
TI  - New standards of care for people with gender dysphoria.

PMID- 22477849
TI  - Primary care mental health and Alma-Ata: from evidence to action.

PMID- 22477851
TI  - Mental health and primary health care.

PMID- 22477852
TI  - Rates of depression among men attending high-HIV-caseload general practices in
      Australia.
AB  - This paper compares rates of current depression among men attending high-HIV
      caseload general practices in New South Wales and South Australia. Current
      depression was assessed by the treating general practitioner (GP), using the nine
      item Patient Health Questionnaire (PHQ-9), and by patient self-reporting. The
      study found that GPs, the PHQ-9 screening tool and patients were equally likely
      to identify current depression. High rates of depression were observed among the
      men attending general practice, with the highest rates among men with HIV and men
      who did not identify as either heterosexual or homosexual.

PMID- 22477853
TI  - Reporting distress and quality of life of patients with diabetes mellitus in
      primary and secondary care in Greece.
AB  - Background and aim This study constitutes an initial attempt at elucidating the
      relationship between quality of life (QoL), health status and psychological
      distress in patients with diabetes mellitus (DM) in Greece, by comparing patients
      with DM registered at a rural primary healthcare centre (PHCC) and those
      attending a diabetes outpatient clinic (DOC) at an urban hospital.Methods Cross
      sectional study. Participants were consecutive, consenting patients with a known
      history of type 2DM(T2 DM), currently registered at either of the two centres.
      All patients were administered the Short Form-36 version 2 (SF-36 v2) and the
      Problem Areas In Diabetes (PAID) questionnaire, and information in relation to
      socio-demographic data and clinical characteristics were also obtained.Results
      Patients with DM had a lower QoL over all domains when compared with general
      population normative data. In addition, mean scores for the SF-36 v2 Physical
      Component Summary (PCS) and Mental Component Summary (MCS) and six subscales of
      the SF-36 v2 demonstrated significant differences between the two participating
      centres (P < 0.0001). The mean PAID score was 19.18 (+/-15.58) for patients from
      the PHCC, versus 40.19 (+/-17.36) for the DOC (P < 0.0001). Lower scores on the
      MCS of the SF-36 v2, and higher scores on PAID in patients with T2 DM were
      related to major co-morbidities, insulin use and duration of DM.Conclusions
      Patients with T2 DM from the urban DOC had significantly higher levels of
      distress and consequently lower levels of QoL compared with patients from the
      rural PHCC. The findings from this study may have important implications with
      regard to the individualisation of patient care in Greece, and encouragement of
      patient participation in the treatment process.

PMID- 22477854
TI  - Patients' experiences of receiving collaborative care for the treatment of
      depression in the UK: a qualitative investigation.
AB  - Objective We explored the experiences of patients who received treatment for
      depression during a 'phase II' platform trial of collaborative care in the
      UK.Method Semi-structured interviews were used to obtain information from 13
      patients receiving collaborative care. Patients from a range of general
      practitioner (GP) practices within the trial were purposively sampled. The
      constant comparative approach within a framework analysis was used to identify
      emerging concepts and key themes.Results Three distinct themes in people's
      experience of collaborative care were identified: (1) the process of
      collaborative care; (2) the content of collaborative care; and (3) staying well.
      These themes were set against a backdrop in which patients described how they had
      been struggling with lowmood. Our central therapeutic ingredients of information
      giving, behavioural activation and medication management were supported by
      patients. Patients expressed reservations about the rigid inflexibility of
      telephone-based treatment.Conclusions While most of the protocol elements were
      supported by patients, we have been able to amend our protocol to allow for
      greater delivery flexibility and more attention to the therapeutic alliance and
      relapse prevention. We are now testing this in a multicentre randomised
      controlled trial.

PMID- 22477855
TI  - Cross-sectional survey of patients in receipt of long-term repeat prescriptions
      for antidepressant drugs in primary care.
AB  - This cross-sectional survey describes the clinical characteristics of 92 patients
      from across 12 general medical practices, in receipt of a long-term repeat
      prescription of an antidepressant for the treatment of depression. Psychiatric
      diagnoses were determined using the Schedule for Clinical Assessment in
      Neuropsychiatry. Fifty-three participants (57.6%) failed to meet criteria for any
      psychiatric diagnosis (95% confidence interval (CI): 47.5-67.7%). Independent
      clinical assessments based upon diagnoses and other clinical data indicated that
      26 (31.0%) participants (95% CI: 28.9-49.7%) had no clear clinical reason for
      continued receipt of an antidepressant. Reasons for the continued use of
      antidepressants in this population require further investigation.

PMID- 22477856
TI  - Depression case management by practice nurses in primary care: an audit.
AB  - Introduction Depression is a common and debilitating condition. A body of
      evidence exists about improving depression outcomes in primary care, using
      collaborative care models. Such approaches, however, have not been routinely
      adopted within general practice settings. In this paper we outline the results of
      an audit of an enhanced care initiative that trained practice nurses to deliver
      such approaches.Method An audit of symptom outcome and satisfaction was conducted
      in depression case-management clinics run by practice nurses. Results were then
      benchmarked against appropriate randomised trial data. The cost of practice nurse
      time devoted to the delivery of the service was estimated by multiplying time by
      unit cost.Results A mean change of 9.07 (standard deviation (SD) 6.67, 95%
      confidence interval (CI) 7.93-10.22, P < 0.001) points on the Patient Health
      Questionnaire (PHQ9) score was observed in those who were using/had used the
      service. Clinical change demonstrated a shift from moderate-to-severe to mild
      depression. The results reflect the changes seen in randomised controlled trial
      data from similar interventions in similar samples, and are superior to expected
      treatment as usual outcomes. Overall, respondents were 'very satisfied' with the
      service on offer. The mean cost of practice nurse time was estimated at L45 per
      patient.Discussion While acknowledging the limitations of audit data, practice
      nurses in general practice appear to be able to offer effective and acceptable
      case management to patients experiencing depression.

PMID- 22477858
TI  - News from WHO and Wonca: new report calls for mental health to be better
      integrated into primary care.

PMID- 22477857
TI  - Mental health education and resources for general practitioners in the UK.

PMID- 22477859
TI  - No mental health without primary care.

PMID- 22477860
TI  - A smoking ban in psychiatric units: threat or opportunity?
AB  - People with severe mental illness (SMI) experience some of the worst physical
      health and die younger than almost any section of the population. Mental health
      professionals have seemed strangely indifferent to this inequality, which in
      other areas of health would be a national scandal. In this editorial we discuss
      the recently introduced smoking ban in inpatient mental health service settings,
      which will offer mental health services an opportunity to implement creative,
      evidence-based strategies to help people with SMI address smoking and nicotine
      addiction. In doing this, we refer to National Institute for Health and Clinical
      Excellence (NICE) guidance. This guidance forms the basis of national smoking
      policies for the general population and forms a starting point for those with
      SMI. Such a strategy will necessarily involve close collaboration with primary
      care, and we specifically examine how this might be achieved.

PMID- 22477861
TI  - Suicide and attempted suicide among South Asians in England: who is at risk?
AB  - Evidence from both large-scale and small-scale studies suggests differences and
      similarities in patterns of suicide and attempted suicide between South Asians
      and the total population in England. Among South Asians, the excess of females
      among both suicides and attempted suicides is even more marked; the traditional
      view of a strong family structure among Asians is confirmed, although cultural
      conflict between generations is apparent. The technique of suicide by burning
      among Asians appears to be waning. Asians who attempt or complete suicide are
      more likely to be suffering from stress, but less likely to have been diagnosed
      as mentally ill. Their psychological problems appear to have been frequently
      overlooked by general practitioners, or not presented to them. Differences in
      religion, with Hindus producing higher rates than Muslims, and demographic,
      geographical, financial and cultural differences, contribute to the need for
      disaggregation and up-to-date research.

PMID- 22477862
TI  - Somatisation and alexithymia in patients with high use of medical care and
      medically unexplained symptoms.
AB  - Background and objective Few reports in the medical literature examine physician
      agreement on a standard assessment for somatisation in primary care patients. We
      describe somatising patients who were subjectively identified by family
      physicians and subsequently classified on the somatisation spectrum by a standard
      evaluation. We also examine the relation between somatisation and
      alexithymia.Method Responding to a brief verbal prompt, family physicians
      referred high-utilising patients 18 years old and older who had 'persistent
      medically unexplained symptoms for at least 6 months' (n = 72). Patients who
      agreed to participate in the study (n = 48) were assessed individually using a
      structured diagnostic interview and two measures of alexithymia.Results All
      participating patients met inclusion criteria for one of two abridged subtypes on
      the somatisation spectrum. Somatisation was not related to
      alexithymia.Conclusions Family physicians subjectively identified patients who
      had somatisation, with a high level of accuracy and without formal screening or
      diagnostic tests. Embedded in a disease-management system, especially an
      electronic version, a brief verbal prompt to physicians to identify patients on
      the somatisation spectrum could potentially realise considerable savings in
      physician time and medical system financial expenditures.

PMID- 22477863
TI  - Variables associated with general practitioners taking on patients with common
      mental disorders.
AB  - Objective The article assesses variables associated with general practitioners
      (GPs) taking on patients suffering from common mental disorders (CMD).Method The
      study is based on a sample of 398 GPs, representative of the 7199 equivalent full
      time GPs practising in Quebec, the second-largest province of Canada. GPs were
      asked to answer a 143-item questionnaire related to their socio-demographic
      profile, clinical practice, patient characteristics, perceived interprofessional
      relationships, quality of care, and support strategies for improving continuity
      of care. Descriptive, bivariate, and multivariate analyses were performed.Results
      This study demonstrates that the following dimensions are associated with GPs
      taking on patients with CMD: (1) their interest and knowledge in dealing with
      such patients; (2) the relative simplicity of treating CMD cases; (3) the quality
      of, and interest in, mental healthcare collaboration; and (4) the availability of
      diversified services. The main enabling variable in GPs taking on CMD patients is
      their interest in mental disorders. Conversely, the principal impeding variable
      is their positive perception of relationships with psychiatric teams.Conclusions
      In accordance with current healthcare reforms, this study reinforces the need to
      promote GP interest and training in mental health care. Increasing GP co
      ordination with psycho-social services, along with developing integrated care
      models including specialised care, is strongly recommended.

PMID- 22477864
TI  - Making fewer depression diagnoses: beneficial for patients?
AB  - Currently, general practitioners actively search for depressive disorders in
      their patients. When they diagnose 'depressive disorder', they tell their
      patients that they have a disease and can be treated accordingly. This is
      probably an important reason for the huge prescription rates of anti-depressants.
      In doing so, general practitioners implement specialised, psychiatric diagnostic
      methods in a setting characterised by patients with symptoms that superficially
      may resemble those of depressive disorder but in reality mainly arise from normal
      problems in everyday life due to losses of valued relations or failure to achieve
      desired goals. We argue that it might be beneficial for patients if general
      practitioners, in a stepped care approach, hold back on specialised methods of
      psychiatry and instead use a more generalist approach as first step, in which
      patients' problems are formulated in their own words, and efforts are directed in
      helping patients regain their self-confidence to solve them. Our arguments for
      directing attention away from diagnosing depressive disorder are: depressive
      disorder is a diagnosis by agreement and therefore relative, so there are other
      ways to look at problems than though psychiatric glasses; depression has unclear
      boundaries with other mental disorders and with normality; depression is often
      not an adequate summary of the real problems of the patient; the patient often
      has a very different conception about what is wrong and often does not agree with
      the proposed presence of a mental disorder; to diagnose depressive disorder may
      have more disadvantages than advantages for the patient;. the efficacy of anti
      depressants is very modest.

PMID- 22477865
TI  - 'It's really a myriad of different signals, not just the textbook': the
      complexities of diagnosing depression in gay men in general practice.
AB  - This paper reports on in-depth interviews with general practitioners (GPs) about
      their views and experiences of diagnosing depression in gay men - some of whom
      are living with HIV - and the broader social contexts in which such a diagnosis
      is located. This analysis is a key outcome of a collaboration between social
      researchers, primary healthcare researchers, GPs and community partners, to
      investigate the management of depression in gay men in primary care settings. As
      the qualitative component of this project, semi-structured in-depth interviews
      were conducted with 16 GPs with high caseloads of gay men, in three geographical
      settings in Australia: Sydney, Adelaide and a rural-coastal town. GPs considered
      the diagnosis and management of depression to be an integral part of primary
      care, especially in gay male patients. They had a heightened sense of awareness
      that depression was common in the group of patients they were seeing. Central to
      diagnosing depression was the ongoing, long-term relationship GPs had with their
      gay male patients. GPs were vigilant and proactively inquired about depression,
      taking into account somatic, social and psychological indicators. In their
      approach to diagnosing depression, GPs considered not only the life circumstances
      of individual patients but also the broader social context of stigma related to
      homosexuality, and the effects that the HIV epidemic has had on individuals,
      especially on gay men who have been living with HIV for a long time.

PMID- 22477866
TI  - Suicide prevention in Nepal: a comparison to Australia-a personal view.
AB  - Suicide is a crisis of unknown proportions in much of the developing world. The
      majority of research into suicide has been done in high-resource countries such
      as Australia, and most intervention protocols have been drawn up using Western
      models. There appear to be a number of differences in the aetiology, presentation
      and treatment options for mental health problems between high-resource and low
      resource countries. This review compares suicide in a high-resource country,
      Australia, and low-resource country, Nepal.Many low-resource countries such as
      Nepal struggle to address barriers to mental health care due to limited mental
      health resources and issues such as stigma, workforce and mental health literacy.
      Issues relating to suicide prevention are raised, contrasting a low-resource
      country, Nepal, with a high-resource country, Australia.

PMID- 22477867
TI  - 'Well doctor, it is all about how life is lived': cues as a tool in the medical
      consultation.
AB  - Introduction During consultations, the perspective of the patient and the family
      physician come together. In order to reach a shared view about the symptoms it is
      important to know the agenda of the patient. Cues (i.e. non-explicit remarks that
      can enclose a special meaning) can serve as a tool to clarify the agenda.Case
      report In this article, we describe a patient with unexplained palpitations
      during vacuuming. During one of the following consultations she provided an
      important psychosocial cue which changed my perspective on her palpitations,
      resulting in a deeper understanding of her symptoms.Discussion Recognition and
      exploration of cues is important for reaching mutual understanding of doctors and
      patients about the symptoms. Moreover, it enhances the therapeutic relationship
      and improves illness outcomes and patient satisfaction.Conclusion Noticing cues
      in the medical consultation helps the doctor to understand the patient's real
      worries. It gives us, as doctors, a better understanding of the patient's
      perspective.

PMID- 22477868
TI  - World Federation for Mental Health: 2009 World Mental Health Day campaign
      highlights need for more attention to mental health services in primary health
      care.

PMID- 22477869
TI  - Primary care and dementia: time to act.

PMID- 22477870
TI  - What should prompt an urgent referral to a community mental health team?
AB  - Background There is often little guidance to advise general practitioners on
      whether a referral to a community mental health team should be classified as
      'urgent' or not.Aims (1) To identify the proportion and appropriateness of
      referrals considered urgent by the referrer; (2) To develop a set of criteria to
      guide what should constitute an 'urgent' referral.Methods One hundred consecutive
      referral letters to a community mental health team were analysed to determine the
      proportion that were considered urgent by the referrer compared to a consensus
      panel of psychiatrists. A Delphi group was then used to develop a set of criteria
      to guide referrers as to what should be regarded as an urgent referral.Results
      Thirty-three percent of referrals were deemed urgent by the referrer, compared to
      17% by the psychiatric consensus panel, with little agreement between the two
      (kappa = 0.021, P = 0.013). Referrals that were made using a single assessment
      process (SAP) form were significantly more likely to be inappropriately marked as
      being urgent (P < 0.001). A set of 12 criteria was developed using the Delphi
      technique.Conclusions There was significant disagreement between the referrers
      and the assessing team as to which referrals required urgent attention. The
      findings justified the creation of guidelines, and this paper outlines a set of
      12 criteria to guide what should prompt an urgent referral.

PMID- 22477871
TI  - The needs of primary care mental health service users: a Q-sort study.
AB  - Background Within scientific and policy literature, the broader needs and
      preferences of the service user are usually described as being relatively
      homogenous for any particular condition. Additionally, despite common adult
      mental health problems being a huge burden to primary care services, there has
      been little research into the client's perspective of their needs regarding such
      difficulties. The aim of this research was thus to uncover the issues and
      preferences for this sample.Method The attitudes of 28 service users were
      explored through use of a Q-methodology approach. This procedure involves
      statistical analysis of the order that participants rank pertinent statements
      associated with the area of study.Results Five independent factors (clusters of
      preferences) were identified. These differed over issues associated with:
      relationships with service providers, access/barriers associated with services,
      information provision, stigma, choices associated with therapy and the care
      pathway, medication and complementary approaches, as well as social
      support.Discussion The study suggests that differing individual needs exist
      within diagnostic categories which, unless considered, may impede service
      engagement. Issues associated with the implications for service delivery for
      these differing clusters of perceived needs and viewpoints are outlined.

PMID- 22477872
TI  - General practitioner attitudes towards referral of eating-disordered patients: a
      vignette study based on the theory of planned behaviour.
AB  - Objective The study examined individual differences between general practitioners
      (GPs) to determine their impact on variations in intention to refer a
      hypothetical patient with disordered eating to specialist eating disorder
      services. The study also examined the impact of patient weight on intention to
      refer.Method GPs within three primary care trusts (PCTs) were posted a vignette
      depicting a patient with disordered eating, described as either normal weight or
      underweight. A questionnaire was developed from the theory of planned behaviour
      to assess the GPs' attitudes, perception of subjective norms, perceived
      behavioural control, and intention to refer the patient. Demographic details were
      also collected.Results Responses were received from 88 GPs (33%). Intention to
      refer the patient was significantly related to subjective norms and cognitive
      attitudes. Together these predictors explained 86% of the variance in the
      intention to refer. GP or practice characteristics did not have a significant
      effect on the GPs' intention to refer, and nor did the patient's
      weight.Conclusion Despite National Institute for Health and Clinical Excellence
      current guidance, patient weight did not influence GPs' decisions to refer. Much
      of the variance in actual referral behaviour may be explained by cognitive
      attitudes and subjective norms. Interventions to reduce this variation should be
      focused on informing GPs about actual norms, and best practice guidelines.

PMID- 22477873
TI  - The introduction of a healthy reading scheme for people with mental health
      problems: usage and experiences of health professionals and library staff.
AB  - Objective This study aimed to explore utilisation of a 'healthy reading' service
      and to offer further insight into improving the processes and uptake of book
      prescribing so that more people have the opportunity to access this
      treatment.Method Semi-structured interviews with librarians and prescribers.
      Collection of routine library data.Results The scheme was thought to have been
      well organised, and borrowings by library users were high. A prescription was
      presented for 17% of borrowings. Health professionals who already used
      bibliotherapy in their practice were particularly positive about the scheme.
      There is potential to increase prescribing from other health professionals,
      especially general practitioners (GPs). Barriers to use included remembering the
      service, lack of knowledge about resources, concerns that patients would find
      resources difficult to use, and the time required within the
      consultation.Conclusion This research showed that the healthy reading scheme
      provided a useful treatment option for patients with mild mental health problems
      and was also well used by library members. Regular reminders about the service
      and training for prescribers have the potential to increase patient access to
      resources. Further research is required to determine whether this model of
      bibliotherapy meets the needs of users of healthy reading materials in accessing
      the service.Healthy reading has a place in stepped care models for improving
      mental health at both community and primary care levels. As well as being used as
      an adjunct therapy it could, in some cases, be an alternative to antidepressant
      prescribing and help reduce waiting lists for more staff-intensive psychological
      therapies.

PMID- 22477874
TI  - Screening for suicidal thoughts in primary care: the views of patients and
      general practitioners.
AB  - Background It has been argued that primary care practitioners have an important
      part to play in the prevention of suicide. However, levels of assessment of risk
      of suicide among patients treated in this setting are generally low.Methods Cross
      sectional survey of general practitioners (GPs) and people being treated in
      primary care who had signs of depression. The study combined open and closed
      questions on attitudes to screening or being screened for suicidal
      ideation.Results One hundred and one of 132 patients took part in the survey and
      103 of 300 GPs completed a questionnaire. A majority of both GPs and patients
      stated that people should be screened for suicidal ideation. However, an
      important minority of patients and GPs stated that asking or being asked such
      questions made them feel uncomfortable. Less than half of GPs had received formal
      training on the assessment of suicide risk. GPs told the researchers that
      barriers to screening included time pressures, culture and language, and concerns
      about the impact that screening could have on people's mental health. One-quarter
      of GPs and one-fifth of patients supported the notion that screening for suicidal
      ideation could induce a person to have thoughts of self-harm.Conclusions GPs and
      family doctors should screen for suicidal risk among depressed patients and
      should receive training on how to do this as part of their general training in
      the assessment and management of mental disorders. Research should be conducted
      to examine what, if any, effect screening for suicidal ideation has on mental
      health.

PMID- 22477876
TI  - Developments in primary mental health care in New Zealand.

PMID- 22477875
TI  - Low-intensity workers: lessons learned from supervising primary care mental
      health workers and dilemmas associated with such roles.
AB  - The UK government's latest primary care mental health initiative, Improving
      Access to Psychological Therapies (IAPT), seeks to achieve its aims partly
      through the extensive use of low-intensity workers (LIWs). As clinical
      supervisors to teams of primary care mental health workers (PCMHWs) already
      offering brief, evidence-based interventions in primary care mental health
      services, we draw on the growing body of literature and our own experience to
      discuss dilemmas associated with the roles of such workers. These concern
      clinical governance, training, supervision and integration into existing
      services. We discuss how IAPT service characteristics may provide solutions to
      some of these dilemmas. We argue that it is unlikely they will be completely
      resolved and that IAPT services, in addressing future challenges, could benefit
      from lessons learned from the PCMHW role.

PMID- 22477877
TI  - Conferences 2009.

PMID- 22477878
TI  - Mental health in primary care gap: now is the time to act.

PMID- 22477879
TI  - Mental health specialty care in the medical home.

PMID- 22477880
TI  - 'The right to health': a viewpoint.

PMID- 22477881
TI  - Primary care and mental health: how can the world respond?

PMID- 22477882
TI  - Detecting mental disorders in primary care.
AB  - Managing mental health problems of people around the world is a major challenge
      for health workers as well as for policy makers. It is a particular problem for
      low- and middle-income countries for many reasons, especially due to lack of
      recourses.A computer-assisted interview, the GMHAT/PC (Global Mental Health
      Assessment Tool - Primary Care) has been developed to assist general
      practitioners and other health professionals to make a quick, convenient, and
      comprehensive, standardised mental health assessment. It has proved to be a
      reliable and valid tool in various studies. Its use by other health professionals
      may help in detecting and managing mental disorders in primary care and general
      health settings more effectively. The article outlines the development and
      potential use of the GMHAT/PC.

PMID- 22477883
TI  - Navigating the mental health and addictions maze: a community-based pilot project
      of a new role in primary mental health care.
AB  - Problem being addressed In a medically under-served rural Canadian community
      where overburdened family physicians provide most of the cae for patients with
      mental illness and substance use problems, providing access to timely and
      effective help for all citizens is a challenge. The care burden of unmet mental
      health needs is experienced throughout the larger community by diverse community
      service providers.Supporting a shared understanding of the needs and challenges,
      and ensuring effective connection and clear communication between diverse
      disciplines in primary care, community services and the formal mental health
      system requires models of service organisation and delivery that go beyond
      traditional clinical roles.In cancer care a navigator model has previously been
      used to address information and service gaps and improve patient experience. We
      wished to evaluate whether a community-supported navigator model could help solve
      some of the challenges for clients and service providers in our community, while
      at the same time allowing data collection that offers a clearer understanding of
      actual service needs.Pre-programme activities Community members formed an
      interdisciplinary community steering committee which met monthly for two years to
      develop and adapt a service and collaborative research model, generate support,
      secure ethical approval and raise funds.Programme description The navigator
      service was embedded in a local family service organisation, the steering
      committee met monthly, and along with the researchers met regularly with
      programme staff and provided support, oversight and development of ethical data
      collection.Navigators provided low barrier access, comprehensive assessment,
      collaborative service planning, and linkage and referral facilitation for any
      individual or family who requested assistance with a mental health or substance
      use concern. Navigators also serve as an information resource for any community
      service provider or family physician needing to assist a client, and collected
      data on local service needs.Conclusions Analysis of quantitative administrative
      data, consented research data, and qualitative interview and survey data
      demonstrated that this community supported navigator service model was effective
      in improving service access, assessment and linkage for citizens with mental
      health and addictions concerns, and connecting a range of community services into
      a more effective network of care. Connecting unattached clients with a primary
      care provider and supporting needs assessment and service planning for patients
      of local family physicians were key navigator functions.

PMID- 22477884
TI  - The Sooke Navigator project: using community resources and research to improve
      local service for mental health and addictions.
AB  - Our rural BC community engaged in an innovative action research project to
      improve access to mental health and addiction (MHA) services for citizens and
      increase connections and communication between primary care, community-based
      providers, and the formal mental health service system. Developed by a community
      based steering committee, our Navigator model is aimed at anyone with mental
      health and addictions issues seeking help in our region. The model includes the
      following services: timely needs assessment, collaborative assistance with need
      based care planning, appropriate information, referral, and linkage facilitation.
      Key features of the Navigator model are discussed, including community
      engagement, guiding principles, and a description of the service is provided. In
      our rural and remote community, a community-supported Navigator model was
      effective in increasing access to comprehensive, strengths-based assessment,
      planning and referral facilitation.

PMID- 22477885
TI  - Integrating mental health into primary care in Sverdlovsk.
AB  - Introduction Mental disorders occur as frequently in Russia as elsewhere, but the
      common mental disorders, especially depression, have gone largely unrecognised
      and undiagnosed by policlinic staff and area doctors.Methods This paper describes
      the impact and sustainability of a multi-component programme to facilitate the
      integration of mental health into primary care, by situation appraisal, policy
      dialogue, development of educational materials, provision of a training programme
      and the publication of standards and good practice guidelines to improve the
      primary care of mental disorders in the Sverdlovsk region of the Russian
      Federation.Results The multi-component programme has resulted in sustainable
      training about common mental disorders, not only of family doctors but also of
      other cadres and levels of professionals, and it has been well integrated with
      Sverdlovsk's overall programme of health sector reforms.Conclusion It is possible
      to facilitate the sustainable integration of mental health into primary care
      within the Russian context. While careful adaptation will be needed, the approach
      adopted here may also hold useful lessons for policy makers seeking to integrate
      mental health within primary care in other contexts and settings.

PMID- 22477886
TI  - Integration of mental health into primary health care in Uganda: opportunities
      and challenges.
AB  - Background Worldwide, a number of reforms have been undertaken with the intention
      of improving access to mental health services. Notable among these is the
      integration of mental health services into primary health care, which has been
      one of the most fundamental healthcare reform recommendations globally.Objectives
      This paper describes the opportunities for and challenges to the integration of
      mental health into primary health care in Uganda, as identified in a wider study,
      aimed at exploring the policy interventions required to address the vicious cycle
      of mental ill-health and poverty.Methods Semi-structured interviews and focus
      group discussions (FGDs) were conducted with purposefully selected mental health
      stakeholders from various sectors. The interviews and FGDs were audio-recorded,
      and transcripts coded on the basis of a pre-determined coding frame. Thematic
      analysis of the data was conducted using NVivo7, adopting a framework analysis
      approach.Results The participants identified a number of opportunities that could
      be exploited to strengthen the integration process. Notable among these was the
      political will and prioritisation of mental health at policy level. Poor
      appreciation of the integration process and attitudinal problems emerged as the
      most pressing challenges for integration of mental health into primary health
      care.Conclusion Irrespective of the various opportunities in place, the
      integration of mental health into primary health care has not yet been fully
      realised, as it faces a number of challenges within and outside the health
      sector. This calls for more concerted efforts to scale up activities for
      effective integration of mental health care into primary health care.

PMID- 22477887
TI  - Integration of child mental health services to primary care: challenges and
      opportunities.
AB  - In the first decade of this new millennium, health professionals are faced with a
      rapidly increasing need for child mental health services and changing models of
      service provision. This gives us a unique opportunity to make provision for
      services where it has not been available before, or to improve upon the existing
      services. This paper examines the challenges and opportunities while attempting
      to integrate child mental health services to primary care.

PMID- 22477888
TI  - Depression recovery from the primary care patient's perspective: 'hear it in my
      voice and see it in my eyes'.
AB  - Purpose This paper aims to contribute to the discussion about the concept of
      recovery from depression from the patient perspective.Methods A structured,
      computer-assisted telephone interview of 576 participants from the Australian
      diamond cohort study who were asked, at the one year follow-up, how they would
      know if someone had recovered from depression. The responses were thematically
      analysed using a modified grounded-theory approach.Results Participants found the
      question challenging on a number of levels, relating to the definition of
      recovery, the subjective nature of getting better from depression, pessimism
      about the possibility of recovery and concerns that people hide how they really
      feel. Participants reported observation and human interaction as crucial to
      deciding if recovery had occurred. This led to three broad groups of indicators
      for recovery: a person's actions, their appearance and their thoughts and
      feelings.Conclusions Australian primary care patients with depressive symptoms
      report using observation and human interaction when trying to decide if someone
      is getting better from depression, leading to a broad range of indicators of
      recovery that include, but are not limited to, the traditional symptom-based
      definitions of depression remission. This data suggests that patients have a rich
      variety of ways of describing recovery, supporting a call for more patient
      centred approaches to setting goals for depression recovery in the primary care
      setting.

PMID- 22477889
TI  - Wonca.

PMID- 22477890
TI  - Wonca Europe: bursaries for Wonca World Conference, Cancun May 2010.

PMID- 22477891
TI  - Report: wonca working party on mental health.

PMID- 22477893
TI  - Mental Health in Family Medicine comes of age.

PMID- 22477892
TI  - Conferences.

PMID- 22477894
TI  - The gap in treatment of serious mental disorder in the community: a public health
      problem.

PMID- 22477895
TI  - Managing depression in a changing primary mental healthcare system: comparison of
      two snapshots of Australian GPs' treatment and referral patterns.
AB  - Background Significant government spending has resulted in substantial changes to
      the Australian primary mental healthcare system. Initially producing the Better
      Outcomes in Mental Health Care (BOiMHC) initiative, this has been replaced by the
      Better Access to Mental Health Care programme, which allows all general
      practitioners (GPs) to refer patients for allied psychological health care under
      Medicare. Aim To examine changes in patient management and referral for care
      following the BOiMHC initiative.Method Comparison of results of a 2006 postal
      survey of Australian GPs examining self-reported management of patients with
      depression with a similar survey conducted in 2001-2002, prior to the BOiMHC
      initiative.Results One hundred and thirty-three (33%) GPs responded. The main
      self-reported strategies for managing patients with depression were similar to
      the previous study: supportive counselling and medication. No significant
      difference was found in rates of self-reported formal training in psychological
      treatments. Significantly higher rates of referral for psychological treatments
      were reported in 2006 than in 2002. Small trends towards higher reported referral
      for and reported use of psychological treatments by GPs registered for the BOiMHC
      initiative were noted when compared with those who were not registered.Conclusion
      While GPs' main reported strategies for managing patients with depression were
      unchanged, reported referral for psychological therapies was significantly higher
      in 2006, possibly reflecting the impact of changes to the primary mental
      healthcare system. Ongoing rigorous evaluation of further changes to the primary
      mental healthcare system are needed to determine whether they deliver effective,
      evidence-based care, and thus to inform future programmes.

PMID- 22477896
TI  - Recession, debt and mental health: challenges and solutions.
AB  - Background During the economic downturn, the link between recession and health
      has featured in many countries' media, political, and medical debate. This paper
      focuses on the previously neglected relationship between personal debt and mental
      health.Aims Using the UK as a case study, this paper considers the public health
      challenges presented by debt to mental health. We then propose solutions
      identified in workshops held during the UK Government's Foresight Review of
      Mental Capital and Wellbeing.Results Within their respective sectors, health
      professionals should receive basic 'debt first aid' training, whilst all UK
      financial sector codes of practice should - as a minimum - recognise the
      existence of customers with mental health problems. Further longitudinal research
      is also needed to 'unpack' the relationship between debt and mental health.
      Across sectors, a lack of co-ordinated activity across health, money advice, and
      creditor organisations remains a weakness. A renewed emphasis on co-ordinated
      'debt care pathways' and better communication between local health and advice
      services is needed.Discussion The relationship between debt and mental health
      presents a contemporary public health challenge. Solutions exist, but will
      require action and investment at a time of competition for funds.

PMID- 22477897
TI  - The family physician and the psychologist in the office together: a response to
      fragmentation.
AB  - It is well known that motives for consulting the family physician, though
      expressed as physical symptoms, often derive from problems needing a holistic,
      psychosocial approach. Progressive differentiation between medicine and
      psychology makes co-operation through referral to the psychologist by the
      physician quite problematic, in terms of both which patients are referred and the
      modalities of referral. Acceptance of psychological referral may, in any case, be
      difficult, due to the social stigma that still surrounds mental distress.The
      authors report a possible solution in an experiment implemented by the
      postgraduate Health Psychology School of the Rome University 'Sapienza',
      entailing joint, direct co-operation between a family physician and a
      psychologist through the psychologist's presence in the doctor's office during
      consultations. This allowed direct access to a psychologist in the absence of any
      filter and without the need for a formal request on the patient's part and a
      biopsychosocial approach to distress. In a small number of cases, more formal
      consultation with the psychologist was proposed. Cases were always discussed
      between the two professionals. To date, the experiment has involved nine
      psychologists and seven physicians over a period of nine years. It appears to be
      entirely feasible, though requiring a period of adaptation between the two
      professionals. Patients have welcomed the presence of the psychologist and, as
      expected, take a broader approach in reporting their distress.An illustrative
      case is presented, in which finding the meaning of a symptom avoided unnecessary
      and costly investigations, and facilitated the patient in taking a new direction
      in his life.

PMID- 22477898
TI  - Mental ability performance among adults with type 2 diabetes in primary care.
AB  - Aim and method The present university-based outpatient clinic, cross-sectional
      study assessed cognitive performance in a sample of 137 adults, with the primary
      objective of determining differences in cognitive performance as a function of
      gender and hypertension status in a type 2 diabetes cohort.Results Approximately
      64% of the sample was 65 years old and younger, and 50 subjects had > 13 years of
      education. Global mental ability scores were relatively similar by age grouping,
      and higher-ordered cognitive functioning and reading literacy were strongly
      correlated, r (98) = 0.62, P < 0.01. Approximately 30% of the sample posted
      global mental ability scores in the slow learner range on tasks measuring
      attention, immediate memory and verbal reasoning. Males achieved higher cognitive
      functioning scores compared to females on multiple mental ability tasks. The
      presence of hypertension was associated with significantly worse cognitive
      performance compared to those subjects without hypertension, t = 2.11, P = 0.03.
      Approximately 57% of the hypertension group was classified as mild cognitive
      impaired.Conclusion While approximately half of the general population can be
      expected to demonstrate an average range of performance on cognitive ability
      measures, such an expectation could be inappropriately generalised to persons
      diagnosed with type 2 diabetes, even among those who were high school educated.

PMID- 22477900
TI  - The rights of the child and primary care mental health.

PMID- 22477899
TI  - Managing schizophrenia in primary care: the utility of remission criteria as
      outcome indicators.
AB  - The shared management of patients with schizophrenia in primary care can only
      succeed if underpinned by valid, easily administered and clinically relevant
      outcome measures. While conditions such as depression and anxiety lend themselves
      to this approach through the development, over a number of years, of patient- and
      observer-rated scales, schizophrenia still lacks the capacity for meaningful
      outcome measures. Recently, two international working groups have developed the
      concept of remission in schizophrenia and recommended a simple, brief and
      clinically valid measure based upon improvement in key symptoms over a specified
      time period. The authors consider this concept and its application to primary
      care both as a commissioning tool and to facilitate shared care of this chronic
      medical condition.

PMID- 22477901
TI  - Emotional distress: an alternative primary care perspective.

PMID- 22477902
TI  - Have Quality and Outcomes Framework Depression Indicators changed referrals from
      primary care to a dedicated memory clinic?
AB  - The proportion of patients referred from primary care to dedicated dementia
      clinics who receive a final diagnosis of dementia is low. Many of these non
      demented patients may have depressive disorders, since depression is the most
      common differential diagnosis of dementia. The UK general practitioner (GP)
      General Medical Services contract, introduced in April 2006, included a Quality
      and Outcomes Framework (QOF) with indicators related to depression. We
      investigated whether introduction of the QOF Depression Indicators changed the
      pattern of referrals from primary care to a dedicated dementia clinic. The
      results indicated that the null hypothesis could not be rejected.

PMID- 22477903
TI  - Depression comorbidity among patients with tuberculosis in a university teaching
      hospital outpatient clinic in Nigeria.
AB  - Background Tuberculosis (TB) remains a leading infectious cause of morbidity and
      mortality throughout the world. Medication non-compliance has been recognised as
      one of the drawbacks in the successful management of this disease. Hence,
      different approaches for ensuring medication compliance have been adopted; these
      include the Directly Observed Therapy Short course (DOTS). TB is associated with
      psychiatric morbidity, particularly depressive disorder, and this has been
      recognised as a cause of poor compliance and a cause of increased morbidity and
      mortality from the disease. Despite this recognition, little attention is paid to
      the identification of depression among TB patients, particularly in the DOTS
      clinics that most of these patients attend. This study was designed to determine
      the prevalence of depression in patients with TB attending the DOTS outpatient
      clinic in a university teaching hospital in Nigeria, and to find out the factors
      that may be associated with this.Method All consenting TB patients attending the
      clinic completed a socio-demographic questionnaire and nine-item Patient Health
      Questionnaire (PHQ-9) designed to screen for depression, especially in outpatient
      and primary care settings.Results Sixty-five patients participated in the study
      of whom 41 (63.1%) were males. The mean age of the respondents was 35.1 +/- 14.4
      (range 15-70 years). Eighteen (27.7%) of the patients had depression, comprising
      14 (21.5%) with mild depression and four (6.2%) with moderate depression. Socio
      demographic factors (age groups, P=0.024; and financial status, P=0.02) and a
      clinical factor (persistent cough, P=0.04) were significantly associated with
      depression.Conclusion Measures to reduce depression among patients with TB should
      include effective symptom control, particularly of coughing, and measures to
      improve the financial status of this group of patients. Financial empowerment of
      patients may reduce depression in them, improve the compliance rate to anti-TB
      medication, and could furthermore bring an improvement to their quality of life.

PMID- 22477904
TI  - Balint groups as 'shared care' in the area of mental health in primary medicine.
AB  - This paper describes how Balint groups can be effective for primary care doctors
      and how leaders of these groups can act as role models in the interdisciplinary,
      experiential learning experience. The paper describes the way Balint activity
      helps the facilitation of a dialogue between mental health professionals and
      primary care physicians. While these groups have been found to improve the
      sensitivity of doctors in their interaction with patients, Balint groups, with
      the joint leadership of professionals from different disciplines, can be seen as
      an effective method to improve primary care and mental health cooperation. These
      issues are discussed and appropriate examples outlined offering an uncommon
      perspective on an interesting topic to promote an integrated, shared model of
      care.

PMID- 22477905
TI  - Comparative, clinical feasibility study of three tools for delivery of cognitive
      behavioural therapy for mild to moderate depression and anxiety provided on a
      self-help basis.
AB  - Background In response to a research recommendation made by a UK healthcare
      policy agency (National Institute for Health and Clinical Excellence (NICE)),
      this study compared the effectiveness of computer-based cognitive behavioural
      therapy (CBT) with other self-help treatment options for mild to moderate
      depression and anxiety.Method Comparative, clinical feasibility study of three
      self-help CBT tools with six-month follow-up. Out of an initial sample of 180
      adults referred by their general practitioners, 100 met the inclusion criteria
      and after consenting to take part were allocated one of three self-help CBT
      tools: the Beating the Blues(r) (BtB) computer programme;(1) workbooks on
      overcoming depression and anxiety; and the Livinglifetothefull free access
      internet website.(2)Results Only 50 of the 100 consented participants completed
      the allocated intervention protocols, however, drop-out rates were not
      significantly different between the groups of participants allocated each of the
      three self-help CBT tools. Adults aged over 24 years (chi(2) = 14.5; df = 2; P =
      0.001) and with symptom duration greater than four years (chi(2) = 3.96; df = 1;
      P = 0.047) were significantly more likely to complete any of the three
      interventions. There was a highly significant reduction in mean Clinical Outcomes
      in Routine Evaluation-Outcome Measure (CORE-OM) score at week eight compared to
      entry in all three groups (t (49) = 9.150; P <=0.001). Adjusting for entry
      scores, there was no significant difference between the three groups in CORE-OM
      score improvement at week eight. There was no significant association between
      CORE-OM score improvement at week eight and number of general practitioner (GP)
      consultations at six months. There was no significant association between whether
      participants completed the programme and number of GP consultations at six
      months.Conclusions The results demonstrated that within a two-month follow-up
      period, three different tools delivering self-help CBT all produced significant
      clinical benefit for adults with mild to moderate depression and anxiety. The
      study had limited statistical power, but none of the modalities for delivering
      supported self-help CBT appeared superior to another. There was no evidence to
      suggest that any of these interventions would be likely to reduce subsequent
      service uptake. Nevertheless, this pilot study has shown sufficient benefit from
      each of the self-administered CBT tools to justify larger trials of their use.

PMID- 22477906
TI  - Effects of an educational outreach campaign (IMPACT) on depression management
      delivered to general practitioners in one primary care trust.
AB  - Objective An educational outreach initiative with general practitioners (GPs)
      within Walsall, led by pharmacists and aimed at delivering evidence-based
      guidance on stepped care management of clinical depression.Methods Standardised
      educational material was produced with key messages and contributions by experts
      on prescribing principles and management of clinical depression based on NICE
      guidance. The primary care pharmacists together with a psychiatrist or other
      professional delivered the training through initial face-to-face meetings with GP
      practices and carrying out follow-up visits.Evaluation Analysis of prescribing
      data (PACT) on antidepressants, which included prescribing of defined daily doses
      (DDD) and net ingredient cost (NIC) of commonly prescribed antidepressants for
      the whole of Walsall teaching Primary Care Trust (tPCT) and comparison with
      prescribing data for the West Midlands and for England during the period June
      2000 to June 2006.Results The use of Fluoxetine increased slightly and the
      prescribing of Dosulepin continued to fall. The prescribing of Escitalopram,
      which had steadily increased prior to the launch of campaign, showed decline,
      resulting in savings of over L50K in the year 2005 to 2006. This was in
      comparison to a relative increase in the prescribing for Escitalopram for the
      same time period in the West Midlands and nationally. Prescribing of Dosulepin
      continued to fall. The total cost of prescribing for the four antidepressants
      fell and theses changes were sustained over the following year.Conclusions The
      educational outreach campaign successfully influenced prescribing behaviour in
      terms of adhering to NICE guidance and cost-effective prescribing, and also
      facilitated improved communication among clinicians at the primary-secondary care
      interface.

PMID- 22477907
TI  - A qualitative study on adolescence, health and family.
AB  - Family is important to both health and adolescence. Adolescence is a time of peak
      health, but there are some important family based risk factors. The aim of this
      study was to explore the perspective of adolescent Iranians on issues of family
      and their health. We used descriptive, qualitative methodology and purposeful
      sampling and interviews for collecting the data. Forty-one participants explained
      their perspectives on health and family. Data were analysed using qualitative
      content analysis. Analysis revealed three categories of risk factors: a widening
      generation gap, effective parenting and family financial situation. To have
      healthy adolescents, both children and parents need more knowledge and better
      skills about adolescent health and development and about social trends. To
      understand adolescents in a more realistic way, parents should develop healthy
      communication to avoid family health problems.

PMID- 22477908
TI  - Primary care mental health: maintaining momentum.

PMID- 22477909
TI  - Overuse of antipsychotic medication in elderly people with dementia? A view from
      general practice.

PMID- 22477910
TI  - Role of the husband's knowledge and behaviour in postnatal depression: a case
      study of an immigrant Pakistani woman.
AB  - Objective This study aims to highlight the subjective experience of an immigrant
      Pakistani woman during postnatal depression (PND), with a special emphasis on the
      husband's knowledge and behaviour towards PND.Methods A face-to-face interview
      was conducted with a woman reporting symptoms of depression on the fourth day
      after delivery. She was evaluated using the Diagnostic and Statistical Manual of
      Mental Disorders, fourth edition (DSM IV)(1) and the Edinburgh Postnatal
      Depression Rating Scale (EPDRS).(2) The evaluations were completed by a qualified
      psychiatrist. The demographic information, personal and family medical history
      and attitude towards the child were the principal issues recorded. In addition,
      five items were used to evaluate the husband's knowledge about PND. The EPDRS
      differences before and after counselling were evaluated using a student t
      test.Results The patient was 32 years old and this was her first experience of
      delivery by Caesarean section. The evaluation for depression confirmed the
      diagnosis of PND and she scored 16 on the EPDRS. The husband's knowledge of PND
      was poor.Conclusion This case study suggests that lack of social support and
      understanding appear to play a vital role in the persistence of symptoms of PND
      among new mothers. Therefore, counselling of couples may be an effective
      additional tool in treating PND.

PMID- 22477911
TI  - Medication error in mental health: implications for primary care.
AB  - Medication errors are associated with significant morbidity and people with
      mental health problems may be particularly susceptible to medication errors due
      to various factors. Primary care has a key role in improving medication safety in
      this vulnerable population. The complexity of services, involving primary and
      secondary care and social services, and potential training issues may increase
      error rates, with physical medicines representing a particular risk. Service
      users may be cognitively impaired and fail to identify an error placing
      additional responsibilities on clinicians. The potential role of carers in error
      prevention and medication safety requires further elaboration. A potential lack
      of trust between service users and clinicians may impair honest communication
      about medication issues leading to errors. There is a need for detailed research
      within this field.

PMID- 22477912
TI  - Detection of dementia in primary care: comparison of the original and a modified
      Mini-Cog Assessment with the Mini-Mental State Examination.
AB  - Background Dementia is considered widely under-detected in primary care, and
      general practitioners (GPs) frequently ask for easy to use tools to assist in its
      early detection.Aim To determine the degree of correlation between the Mini-Cog
      Assessment (Mini-Cog) as performed by GPs and the Mini-Mental State Examination
      (MMSE).Design of study This was a prospective study (2005, 2006) comparing two
      cognitive screening instruments.Setting Ten general practices in Austria, with
      patients with a hitherto undiagnosed suspicion of dementia seen
      consecutively.Method Sensitivity, specificity and positive and negative
      predictive values (PPVs and NPVs) of the Mini-Cog (applying both a colour-coded
      and the original rating method) were assessed for degree of correlation with the
      MMSE. In phase one GPs examined patients suspected of having dementia using the
      Mini-Cog; in phase two a neurologist retested them applying the MMSE, a clock
      drawing test (CDT) and a routine clinical examination. A questionnaire on the
      practicability of the Mini-Cog was answered by GPs.Results Of the 107 patients
      who participated 86 completed the whole study protocol. The Mini-Cog, as
      performed by the ten GPs, displayed a sensitivity of 0.85 (95% CI: 0.71, 0.98), a
      specificity of 0.58 (95% CI: 0.46, 0.71), a PPV of 0.47 (95% CI: 0.33, 0.61) and
      an NPV of 0.90 (95% CI: 0.80, 0.99) as against the MMSE carried out by
      neurologists. The GPs judged the Mini-Cog useful and time saving.Conclusion The
      Mini-Cog has a high sensitivity and acceptable specificity in the general
      practice setting and has proved to be a practicable tool for the diagnosis of
      dementia in primary care.

PMID- 22477913
TI  - Attitude toward depression, its complications, prevention and barriers to seeking
      help among ethnic groups in Penang, Malaysia.
AB  - This study aims to explore attitudes towards, complications of and preventive
      measures for depression and the barriers that result in delays in seeking help
      among the various ethnic groups in Penang, Malaysia. In June 2007 a questionnaire
      based survey was undertaken in Penang. Face-to-face interviews were conducted,
      and 1855 respondents were approached to participate in the study by adopting a
      cluster random sampling method. A 25-item questionnaire was used to explore
      public attitudes towards, complications of and preventive measures for depression
      and delays in seeking help. A total of 1149 (61.94%) showed willingness to
      participate in the survey. Ethnically, 490 (42.6%) of the respondents who
      participated in the survey were Malay, while 413 (35.9%) were Chinese, 149 (13%)
      Indian and 97 (8.4%) from other ethnic minorities. The mean age of the
      respondents was 30 years (SD +/- 11.5). In evaluating public attitudes, the
      majority (n = 910, 79.2%) agreed with the statement that family and friends can
      enhance the depression recovery process by providing more care and attention to
      the patient and this was found to be statistically significant (P <=0.001). More
      than one-third of the respondents (n = 437, 38.0%) perceived depression as a
      normal medical condition and believed that it subsides automatically. The
      majority (n = 830, 72.2%) stated that depression results in social problems,
      while some felt that it can lead to raised blood pressure (n = 518, 45.1%). In
      terms of prevention, most of the respondents indicated that one can prevent
      depression by maintaining a good social life. In evaluating the barriers to
      seeking professional help, the majority (n = 582, 50.7%) stated that they did not
      believe they were at risk, with the next largest group identifying a lack of
      awareness regarding the signs and symptoms. However, a positive attitude was
      observed towards the complications and prevention of depression. Initiatives to
      increase mental health literacy will prove fruitful in neutralising the negative
      public perceptions towards the treatment of depression and barriers to seeking
      professional help.

PMID- 22477915
TI  - Portuguese national mental health plan (2007-2016) executive summary.

PMID- 22477914
TI  - Research in primary care mental health in Greece.

PMID- 22477916
TI  - Acculturation, metaphor and mental health in primary care.

PMID- 22477917
TI  - The meaning and the story: reflecting on a refugee's experiences of mental health
      services in Australia.

PMID- 22477918
TI  - Evolution of the prevalence and incidence of consumption of antidepressants in a
      Spanish region (2002-2007).
AB  - Background The treatment of depressive disorders involves the administration of
      drugs of proven efficacy at the correct doses and for specific periods of time,
      in conjunction with psychotherapeutic support.Aim To assess the evolution of the
      consumption of antidepressants in the Health Region of Lleida (Spain).Method A
      retrospective cohort study of the antidepressant medication prescribed via the
      Spanish National Health System in the Health Region of Lleida between 2002 and
      2007. The variables recorded in the study were age, sex, number of patients in
      antidepressant treatment in the Health Region of Lleida, length of treatment and
      type of drug. The prevalence of the population of the health region who were
      receiving antidepressant drugs and the incidence for each particular year was
      calculated.Results The mean prevalence of patients in treatment with
      antidepressant drugs was 8.5% (5% in men and 12.1% in women). The highest
      prevalence was observed in the higher age groups. By therapeutic groups,
      selective serotonin reuptake inhibitors (SSRIs) were the most frequently
      prescribed, five times more than the next group, tricyclics/heterocyclics. The
      follow-up assessment of the medication prescribed showed that one out of every
      four patients did not continue treatment after the first month, and 38.4% did not
      continue after three months. Very few were treated for more than six
      months.Conclusion This study stresses the high rate of antidepressant treatment
      in the older women's group. One of every four treatments initiated did not last
      more than one month. Over the six-year period, 16 506 patients dropped out of
      treatment.

PMID- 22477919
TI  - Understanding the expanding role of primary care physicians (PCPs) to primary
      psychiatric care physicians (PPCPs): enhancing the assessment and treatment of
      psychiatric conditions.
AB  - Aim In the current healthcare system primary care physicians (PCPs) have, in
      effect, become the primary psychiatric care physicians (PPCPs) for many of their
      patients. Being the PPCP in an already busy and stressful medical industry
      presents additional time management and treatment challenges to successfully
      manage patients' medical and psychiatric needs. The aim of the study was to
      ascertain PCPs' psychiatric assessment and treatment practices and to determine
      the extent to which PCPs have a need for using a structured psychiatric
      assessment tool.Method We sent 300 PCPs a survey to examine their psychiatric
      assessment and treatment practices. A one-page questionnaire was used to inquire
      about PCPs' psychiatric care practice habits including types of conditions
      treated, psychiatric medications prescribed, assessment methods used, interest in
      using a structured assessment tool and referral sources used. Sixty-eight usable
      surveys (23%) were returned.Results PCPs identify approximately one-third of
      their patients as mental health patients. They are treating a wide range of
      psychiatric conditions and prescribing a variety of psychiatric medications. The
      vast majority are using traditional clinical interviewing as their primary method
      of psychiatric assessment. However, the majority were willing to use a structured
      psychiatric assessment tool.Conclusion PCPs are serving a useful role in
      providing psychiatric treatment to many of their patients. Using a more
      structured psychiatric assessment method in practice could ultimately strengthen
      the assessment and treatment of psychiatric conditions in primary care settings.

PMID- 22477920
TI  - Mental health literacy towards depression among non-medical students at a
      Malaysian university.
AB  - Background The aim of the present study was to evaluate the knowledge and
      perception of depression among students of University Sains Malaysia (USM), in
      Penang, Peninsular Malaysia.Method Face-to-face interviews were conducted using a
      pre-validated 21-item questionnaire among students at USM.Results A total of 500
      respondents participated in the survey comprising 24.6% (n=123) males and 75.4%
      (n=377) females. Half (50.0%, n=250) were Malays, followed by Chinese (44.0%,
      n=220) and Indians (6.0%, n=30). Whilst exploring the respondents' knowledge of
      the symptoms of depression, it was found that Chinese females had a comparatively
      better knowledge (P=0.058) of the symptoms of depression in comparison with
      Malays and Indians. Overall, social issues were attributed as the possible cause
      of depression. A cursory knowledge level was observed regarding medication for
      depression. Female students were more inclined towards the use of alternative and
      traditional medicines. However, with regard to seeking professional help,
      consultation with a psychiatrist was preferred by the majority.Conclusion
      Overall, a moderate level of knowledge about the symptoms of depression and a
      cursory knowledge of its therapy were observed. Those with personal experience of
      depression had better knowledge of the symptoms and therapy. Alternative
      treatments and traditional medicines were also favoured. There is a risk that
      this may affect the ability of Malaysian youths to seek evidence-based mental
      health care.

PMID- 22477921
TI  - Integration of mental health into primary care and community health working in
      Kenya: context, rationale, coverage and sustainability.
AB  - Integration of mental health into primary care is essential to meet population
      needs yet faces many challenges if such projects are to achieve impact and be
      sustainable in low income countries alongside other competing priorities. This
      paper describes the rationale and progress of a collaborative project in Kenya to
      train primary care and community health workers about mental health and integrate
      mental health into their routine work, Within a health systems strengthening
      approach. So far 1877 health workers have been trained. The paper describes the
      multiple challenges faced by the project, and reviews the mechanisms deployed
      which have strengthened its impact and sustainability to date.

PMID- 22477922
TI  - Feasibility of guided cognitive behaviour therapy (CBT) self-help for childhood
      anxiety disorders in primary care.
AB  - Anxiety disorders in childhood are common, disabling and run a chronic course.
      Cognitive behaviour therapy (CBT) is effective but expensive and trained
      therapists are scarce. Guided self-help treatments may be a means of widening
      access to treatment. This study aimed to examine the feasibility of guided CBT
      self-help in primary care for childhood anxiety disorders, specifically in terms
      of therapist adherence, patient and therapist satisfaction and clinical
      gain.Participants were children aged between five and 12 years referred to two
      primary child and adolescent mental health services (PCAMHSs) in Oxfordshire, UK,
      who met diagnostic criteria for a primary anxiety disorder. Of the 52 eligible
      children, 41 anxious children were assessed for anxiety severity and interference
      before and after receiving CBT self-help delivered via a parent (total therapy
      time = five hours) by primary mental health workers (PMHWs). Therapy sessions
      were rated for treatment adherence and parents and PMHWs completed satisfaction
      questionnaires after treatment completion. Over 80% of therapy sessions were
      rated at a high level of treatment adherence. Parents and PMHWs reported high
      satisfaction with the treatment. Sixty-one percent of the children assessed no
      longer met the criteria for their primary anxiety disorder diagnosis following
      treatment, and 76% were rated as 'much'/'very much' improved on the Clinical
      Global Impression-Improvement (CGI-I) scale. There were significant reductions on
      parent and child report measures of anxiety symptoms, interference and
      depression. Preliminary exploration indicated that parental anxiety was
      associated with child treatment outcome. The findings suggest that guided CBT
      self-help represents a promising treatment for childhood anxiety in primary care.

PMID- 22477923
TI  - Substance misuse and primary care mental health.

PMID- 22477924
TI  - Psychosocial stress and abdominal pain in adolescents.
AB  - Children and adolescents may express psychiatric symptoms via somatic complaints.
      Likewise, children with chronic somatic illnesses are likely to experience
      psychiatric sequelae. We report three cases of adolescents who were admitted to
      general paediatrics services for abdominal pain and/or nausea and vomiting with a
      negative medical workup. In each case, a clear psychosocial stressor was evident.
      It is possible that somatic symptoms without clear medical causes may reflect
      psychosocial stress, but it is difficult to discern whether the psychosocial
      issues preceded the somatic complaints or were a result of them. Making an
      accurate diagnosis is difficult, and broaching such a subject with patients and
      their families is a delicate matter. More research is needed to determine
      appropriate screening tools for identifying cases where psychosocial stress may
      play a relevant role in symptom presentation, as well as potential treatment
      modalities for such cases.

PMID- 22477925
TI  - The cost of somatisation among the working-age population in England for the year
      2008-2009.
AB  - Medically unexplained symptoms are one of the most commonly encountered symptoms
      across all healthcare settings. They are also responsible for a large proportion
      of disability in the workforce and decreased quality of life. These patients
      represent an important clinical phenomenon with considerable direct and indirect
      economic consequences.This study aims to calculate the economic burden of
      somatisation among English adults in 2008-2009.Using existing literature,
      estimates of prevalence, healthcare use and disability were combined in order to
      calculate the annual cost of healthcare use and productivity loss associated with
      these patients in excess of non-somatising patients.Based on the results of our
      analysis, the incremental health care cost incurred by somatising patients is
      estimated to be L3 billion. This represents approximately 10% of total NHS
      expenditure on these services for the working-age population in 2008-2009. The
      cost of sickness absence and decreased quality of life associated with these
      patients amounts to over L14 billion.By highlighting the magnitude of this
      phenomenon at each level of the health system and the considerable impact of non
      healthcare costs, this study serves to draw attention to a group of patients who
      are frequently unrecognised or misdiagnosed by physicians who tend to repeatedly
      pursue organic possibilities through multiple tests, procedures and operations.
      As economic perspectives play an increasing role in healthcare planning, the
      reduction of health care use and improvement of functioning among this group of
      patients should be a major goal. In order to realise these goals, changed
      pathways and behaviour in primary and secondary care are needed, along with
      improved access to psychological therapy services.

PMID- 22477926
TI  - Biofeedback in medicine: who, when, why and how?
AB  - Biofeedback is a mind-body technique in which individuals learn how to modify
      their physiology for the purpose of improving physical, mental, emotional and
      spiritual health. Much like physical therapy, biofeedback training requires
      active participation on the part of patients and often regular practice between
      training sessions. Clinical biofeedback may be used to manage disease symptoms as
      well as to improve overall health and wellness through stress management
      training. Research has shown that biofeedback interventions are efficacious in
      treating a variety of medical conditions, and many Americans are turning to
      biofeedback and other less traditional therapies for their routine
      healthcare.Clinical biofeedback training is growing increasingly popular in the
      USA, as many people are seeking out relatively new approaches to healthcare. This
      article provides an overview of clinical biofeedback training, outlines two
      models of training, details research which has established how effective
      biofeedback is in patients with a given disease, and describes who should be
      referred for biofeedback training.

PMID- 22477927
TI  - Quality of life in mothers of children with oppositional defiant symptoms: a
      community sample.
AB  - Background Children with oppositional defiant symptoms (ODS) are highly related
      to parental stress, especially in mothers. This study is the first to investigate
      the quality of life (QOL) of mothers of children with ODS in a community
      sample.Methods Randomly selected mothers of children attending an elementary
      school were contacted, and 387 who completed the questionnaire participated in
      this study. The children's ODS status was determined by the maternal rating of
      the Chinese Swanson, Nolan, and Pelham rating scale, version IV. The mothers' QOL
      was estimated by maternal reports from the World Health Organization Quality of
      Life - BREF (WHOQOL-BREF) instrument. The relationship between the children's ODS
      status and maternal QOL was examined by analysis of covariance (ANCOVA) with the
      participants' sociodemographic factors as covariables.Results Sixty-three
      children, mostly boys, met the screening criteria for ODS. The positive screening
      rate for ODS was 16.49%. The children's ODS status was a significant predictor
      for the maternal physical capacity, psychological wellbeing and environment
      domains of QOL. Mothers of children with ODS who rented a house were younger and
      had lower education levels and worse QOL in all domains.Conclusion A high
      positive screening rate for ODS children in the elementary school and a
      relationship between poor maternal QOL and children's ODS were found in this
      study. Routine screening for ODS in children and mental health services for these
      children and their mothers are warranted.

PMID- 22477928
TI  - Readability of standard appointment letters.
AB  - Introduction and aims The first contact a clinical service has with a patient is
      often an appointment letter and thus it is important that this letter is written
      in a way which is accessible. One concern is to write in language which is easily
      able to be read by the majority of recipients. A simple initial way to assess
      this is by using measures of readability of text.Methods We applied measures to
      examine the readability of appointment and administrative letters sent to young
      people by clinicians in the Young People's Department at the Royal Cornhill
      Hospital in Aberdeen.Results Many letters were unlikely to be understood by our
      youngest patients. We revised the letters to meet an agreed standard of
      readability, and agreed their routine use within the team. All letters were
      significantly improved on standard measures of readability and were preferred by
      patients.Conclusions The methods used are feasible, easily available and may be
      helpful to clinicians working in other specialties to improve the level of
      readability of written communication. This will help patients and families in
      their first contact with any clinical service.

PMID- 22477929
TI  - Depression screening as a quality indicator.
AB  - Objective Although practice guidelines for depression screening are evidence
      based, with their development relying on reviews of controlled studies, their
      adaptation and use as quality indicators have not been subject to rigorous study.
      This paper will therefore review the evidence supporting this practice.Methods A
      rational evaluation was carried out on both controlled studies and other sources
      of evidence related to the technical, clinical and policy assumptions underlying
      the use of depression screening guidelines as quality indicators.Results 1)
      Technical assumptions: depression screening could be used as a quality indicator.
      Current information technology does not allow accurate determination of who would
      benefit from being screened, whether they actually were screened, or the optimal
      percentage that should be screened. 2) Clinical assumptions: depression screening
      would improve outcomes. The evidence suggests that although depression screening
      might increase the diagnosis of depression, depressed patients so recognised tend
      to be less ill, less in need of treatment, or less likely to benefit from
      treatment, while screening, in the absence of other interventions, does not
      improve outcomes. 3) Policy assumptions: depression screening should be a focus
      of quality improvement. However, relative to other preventative measures,
      depression screening is a low priority. It does not meet usual cost-effectiveness
      criteria. There are more robust interventions for depression (i.e. collaborative
      care) that could be a focus of quality improvement efforts.Conclusion Although
      routine depression screening may be an acceptable practice guideline, its use as
      a quality measure is not supported.

PMID- 22477931
TI  - World mental health day.

PMID- 22477930
TI  - Physical healthcare of people with severe mental illness: everybody's business!
AB  - Aim People with severe mental illness are at higher risk of physical health
      problems. Guidelines recommend annual monitoring. An audit cycle was completed on
      individuals with severe mental illness under the care of an early interventions
      in psychosis (EIP) service to evaluate and improve physical health monitoring
      practice.Methods The number of patients who had undergone a physical health check
      in the previous year, and those having a record of it in their EIP notes, was
      examined. Interventions made between baseline audit and re-audit included
      improving awareness within the multidisciplinary EIP mental health team about the
      importance of physical health monitoring of people with severe mental illness and
      liaison with primary care health services.Results The number of patients
      undergoing at least one annual physical health check increased from 20% to 58%.
      Among patients who had undergone a physical health check at re-audit, a record of
      some or all the checks was available in the notes for 75% of patients.Clinical
      implications There is a need to improve awareness among mental health
      professionals about the importance of the physical health of people with severe
      mental illness and to make appropriate organisational changes.

PMID- 22477932
TI  - WPA Thematic Conference: Mental Health and Family Medicine Professionals: Working
      Together, 9-11 February 2012, Granada.

PMID- 22477933
TI  - Mental health and chronic physical illnesses: the need for continued and
      integrated care - World Mental Health Day 2010.

PMID- 22477934
TI  - Correlation between mental health co-morbidity screening scores and clinical
      response in collaborative care treatment for depression.
AB  - The hypothesis for this paper is that adult patients who have higher screening
      scores for mental health co-morbidities and depression have a greater likelihood
      of not responding to treatment with collaborative care management (CCM) for their
      depression within six months.For the 334 patients in this study, the primary
      endpoints were if the patient was in remission at six months (PHQ-9 score <5) or
      if they were non-responsive (NR) (PHQ-9 >50% of baseline score). Initial
      evaluation included screening for alcoholism (AUDIT), anxiety (GAD-7) and bipolar
      disorders (MDQ).The differences in marital status, percentage of minority
      patients, gender, initial PHQ-9 and AUDIT scores were not statistically
      significant. Mood Disorders Questionnaire (MDQ) screening was more likely to be
      negative for the group in remission (96.2% vs 90.0%, P=0.049) and positive for
      the NR group (8.0% vs 2.1%, P=0.026). GAD-7 screening was significantly lower in
      the remission group (9.85) than in the NR group (11.53, P=0.009).Results of
      multiple logistic regression analysis demonstrated that age, gender, race,
      marital status, PHQ-9 score and AUDIT score were not related to the odds of being
      NR. A one-point higher GAD-7 score was associated with approximately 6% higher
      adjusted odds of being NR. Patients with a positive MDQ were associated with
      elevated odds of non-response (adjusted OR=3.4714, P=0.044) when controlling for
      all other variables.A higher initial screening score for anxiety or bipolar
      disorder is associated with a statistically significant increase in the relative
      risk of patients in CCM not responding to current treatments for depression
      within six months.

PMID- 22477935
TI  - Family perceptions of post-deployment healthcare needs of Iraq/Afghanistan
      military personnel.
AB  - Nearly 40 000 service members returning from Iraq and Afghanistan have suffered
      traumatic injuries, with over 300 000 at risk for post-traumatic stress disorder
      (PTSD) or other psychiatric problems. These veterans face numerous post
      deployment health concerns, sharing substantial burdens with their families.
      Although many rely upon community-based health care, little is known about how
      these individuals present at family medicine clinics for perceived medical and
      psychological issues. We surveyed 347 patients during visits at six clinics, and
      respondents reported whether they,a family member or a close acquaintance had
      been deployed since 2001. Patients identified traumatic military experiences,
      plus any attributable health or social problems. The mean patient age was 47.5
      years, with 71% women and 55% Hispanic individuals. Nearly one-quarter reported
      family members serving overseas while 52% knew someone deployed. Significant
      events included nearby explosion (21%) or combat injury (9%), along with a
      variety of other incidents. Among the half of individuals perceiving significant
      health or social ramifications, the most prevalent consequences were PTSD,
      depression and alcohol abuse. Divorce or marital problems were noted by13%, while
      many reported employment, legal or other difficulties. This study offers insights
      into post-deployment needs of military personnel and subsequent problems reported
      by family members. A high prevalence of traumatic combat events translated into
      serious health needs, plus social disruptions for veterans and their loved ones.
      As the long-term problems disclosed by returning service personnel continue to
      ripple across community clinics and other health systems, effective treatment
      planning mandates coordinated attention from multiple providers and service
      organisations.

PMID- 22477936
TI  - Factors associated with adolescents' smoking experience and staying tobacco free.
AB  - Introduction It is not expected that those who did not smoke during their
      adolescent years will start to smoke later in life. This study was planned to
      learn the thoughts of Turkish adolescents about staying tobacco free.Methods A
      descriptive study was conducted in 2007 with 866 adolescents aged 11 to 14 years.
      On a self-administered questionnaire, non-smoker students answered both multiple
      choice and open-ended questions about why they would not smoke in the future. The
      Chi-square test and logistic regression analysis was used for statistical
      assessment. For the answers to the open-ended questions, thematic analysis was
      applied.Results The mean age of the participants was 12.84 +/- 1.14 years. The
      incidence of a smoking experience at least once in the participant's lifetime was
      12% and the rate of current smoking was 3.6%. The most listed reasons for staying
      tobacco free were health problems directly related to smoking (64%), such as 'it
      can cause diseases' or 'it kills', negative effects of smoking other than health
      (51%), such as 'it smells bad' or 'it is toxic', and some subjective judgements
      related only with their self perceptions, such as 'I am happy and healthy' or 'it
      affects growth negatively' (20%).The most well-known problem related to tobacco
      use was lung cancer and the least well-known problems were bladder cancer and
      chronic bronchitis. Most of the smoking students (68%) were not aware that second
      hand smoking was harmful (p=0.003). There were significant correlations between
      smoking experience and male gender, having a smoker in the household and low
      educational level of the mother or the father (p=0.000, p=0.018, p=0.022, p=0.044
      respectively).Conclusion We suggest that the beliefs and perceptions of
      adolescents about smoking should be given as much consideration as the negative
      effects of cigarettes in planning smoking free messages.

PMID- 22477938
TI  - Patient characteristics that may predict the likelihood of the presence of mental
      health problems in patients attending the general outpatient clinic of a tertiary
      hospital in South-South Nigeria.
AB  - Background A considerable number of patients seen in general outpatient clinics
      (GOPC) are known to suffer from psychiatric rather than physical disorders.
      Studies have shown that doctors working in these clinics have difficulty in
      making accurate ratings of mental health problems in their patients and have poor
      knowledge of psychiatric diagnosis. Accurate recognition of psychiatric symptoms
      in a patient is essential for specific diagnosis and successful management. There
      is a need for the use of an easy tool such as the12-item General Health
      Questionnaire (GHQ-12) for screening and identification of psychopathologies
      especially in a busy clinic setting like the GOPC. Aside from psychometric
      screening tools, patients' sociodemographic characteristics such as gender, age,
      marital status, occupation, education etc. have been found to be of value in
      predicting those at risk.Objectives This study seeks to correlate GHQ 'caseness'
      with sociodemographic factors and to compare physician diagnosis with GHQ
      diagnosis.Subjects and method Three-hundred and twenty-two respondents were
      recruited for the study by a systematic random sampling method. Using a cut off
      score of three on both the English and Efik translation versions of the GHQ-12,
      'cases' and 'non-cases' generated were compared with the same classification as
      identified by the GOPC doctors. Identification rates for both groups were
      calculated and the coefficients determined using a two-by-two contingency table.
      Sociodemographic correlates were determined by statistical comparison of the
      classifications in both groups.Results Statistically significant differences in
      sociodemographic characteristics of respondents were found for age (chi(2)=48.97;
      P <0.05) and education (chi(2)=45.64; P=0.05) using their GHQ-12 scores, and for
      occupation (chi(2)=37.90; P <0.05) among those seen by the GOPC doctors. A
      further comparison of identified 'cases' and 'non-cases' by doctors again
      revealed significant difference for age (chi(2)=7.151; P <0.05). Sex as a
      sociodemographic characteristic showed no statistically significant difference
      though a greater percentage of females (57.3%) were observed as 'high scorers' as
      compared to their male counterparts (42.7%). The GHQ-12 identified 46.6% 'cases'
      while the GOPC doctors identified 6.8% among the attendees with a diagnostic
      sensitivity of 8% and a specificity of 94%, respectively.Conclusion Belonging to
      the 18-39 years age group, being employed and having less than 12 years of
      education were the patients' characteristics that suggested the likelihood of the
      presence of mental health problems.This study also revealed that despite the high
      proportion of psychiatric morbidity (46.6%) in the GOPC of the University of
      Calabar Teaching Hospital (UCTH) rate of detection by the clinic doctors was low
      (6.8%).It is recommended that primary care doctors should be alerted to the
      possibility that clinically significant psychiatric morbidity may be present in
      GOPC attendees. The correlation between patients' sociodemographic parameters and
      presence of mental health problems could be informative and should be given
      adequate attention during consultation.

PMID- 22477937
TI  - Self-efficacy and the promotion of health for depressed single mothers.
AB  - Single mothers are a vulnerable population at risk for poor mental and physical
      health. This paper discusses the mental and physical health of single mothers, as
      well as the psychosocial and socio-economic risk factors placing single mothers
      at risk for poor health outcomes. Some of these include, gender, income level,
      educational status, social support, stress and certain personality
      characteristics. Theoretical models with the potential to explore ways to promote
      health in depressed single mothers will also be presented. The paper concludes
      with the application of these models to primary prevention and the promotion of
      health for single mothers along with recommendations for future research.

PMID- 22477940
TI  - The coming of age: Mental Health in Family Medicine.

PMID- 22477939
TI  - Depression and subjective quality of life among outpatients with diabetes
      mellitus at a teaching hospital in Nigeria.
AB  - Objective To determine the relationship between depression and the subjective
      assessment of quality of life (QoL) in a sample of patients with diabetes
      mellitus (DM) attending outpatient clinics at a regional university teaching
      hospital in Nigeria.Methods A cross-section of 200 patients were administered the
      depression module of the Schedule for the Clinical Assessment in Neuropsychiatry
      (SCAN) and the World Health Organization Quality of Life assessment - brief
      version (WHOQoL-Bref) over a two-month study period.Results A major depressive
      disorder (MDD) was diagnosed in 30% of patients. MDD was significantly associated
      with lower mean scores on the facets of overall QoL (p<0.01) and health
      satisfaction (p<0.01), but not in the domains of physical health (p=0.67),
      psychological health (p=0.59), environment (p=0.70), or social relations (p=0.58)
      of the WHOQoL-Bref.Conclusion Depression is associated with a poorer subjective
      assessment of QoL among DM patients in Nigeria.

PMID- 22477941
TI  - Not yet explained symptoms.

PMID- 22477942
TI  - Medically unexplained symptoms in primary care: how can doctors help, not hinder?

PMID- 22477943
TI  - Democratising and vitalising family practice by patient-centred medicine.

PMID- 22477944
TI  - Coping style in primary care adult patients with abridged somatoform disorders.
AB  - Background and objective Empirical data are scarce regarding the adaptive
      response to stress for patients with somatoform disorders. Our objective was to
      identify the preferred coping strategies of patients with abridged somatisation,
      a common condition in primary care. Because of the functional impairment
      associated with somatisation, we predicted a preference for less effective,
      emotion-focused coping strategies over more effective, problem-focused
      adaptations.Design We conducted a cross-sectional, observational study of
      physician referred primary care patients who presented with persistent, medically
      unexplained, physical symptoms. Patients were classified into two abridged
      somatisation groups by symptom frequency and duration, as determined by the
      Diagnostic Interview Schedule. The groups were compared with each other and with
      a non-clinical reference group; outcome variables were eight emotion- and problem
      focused strategies, as measured by the Ways of Coping Questionnaire.Results Of
      the 72 eligible individuals, 48 participated in the study. Median age was 48
      years and 75% of patients were women; 26 had somatic syndrome and 22 had a
      subthreshold somatising level. Patients with abridged somatisation disorders
      preferred emotion-focused coping strategies - typically detachment and impact
      minimisation, wishful thinking and problem avoidance.Conclusions Patients with
      abridged somatising disorder responded to stress with predominantly emotion
      focused strategies, which may be associated with a lower level of positive
      adaptive outcome. Our findings suggest that patients with abridged somatising
      disorders might benefit from emphasis on problem-focused coping strategies,
      delivered through primary care, to improve quality of life and decrease
      healthcare utilisation costs.

PMID- 22477945
TI  - The treatment of patients with medically unexplained symptoms in primary care: a
      review of the literature.
AB  - Medically unexplained symptoms (MUS) are among the most common and frustrating in
      primary care. Our goal was to review published evidence to guide busy general
      practitioners working with a culturally diverse, challenging patient population
      coping with MUS. A search of PubMed and PsycINFO from 1985 to the present was
      conducted using MUS and related terms.The literature was then organised into
      subcategories based on its relevance to primary care. We conclude with a
      description of gaps in the literature based on the literature review and the
      clinical experience of the authors.

PMID- 22477946
TI  - Explanatory models of medically unexplained symptoms: a qualitative analysis of
      the literature.
AB  - Background Medically unexplained symptoms (MUS) are common in primary health
      care. Both patients and doctors are burdened with the symptoms that negatively
      affect patients' quality of life. General practitioners (GPs) often face
      difficulties when giving patients legitimate and convincing explanations for
      their symptoms. This explanation is important for reassuring patients and for
      maintaining a good doctor-patient communication and relationship.Objective To
      provide an overview of explanatory models for MUS.Study design We performed a
      systematic search of reviews in PsycINFO and PubMed about explanatory models of
      MUS. We performed a qualitative analysis of the data according to the principles
      of constant comparative analysis to identify specific explanatory models.Results
      We distinguished nine specific explanatory models of MUS in the literature:
      somatosensory amplification, sensitisation, sensitivity, immune system
      sensitisation, endocrine dysregulation, signal filter model, illness behaviour
      model, autonomous nervous system dysfunction and abnormal proprioception. The
      nine different explanatory models focus on different domains, including somatic
      causes, perception, illness behaviour and predisposition. We also found one meta
      model, which incorporates these four domains: the cognitive behavioural therapy
      model.Conclusion Although GPs often face difficulties when providing explanations
      to patients with MUS, there are multiple explanatory models in the scientific
      literature that may be of use in daily medical practice.

PMID- 22477947
TI  - What lies beyond the pain? A case report.
AB  - The majority of people have back pain at some point in their lives and most are
      cured without any intervention. However, some patients develop chronic back pain
      and persistent disability. There is strong evidence that psychological factors
      significantly correlate with the development of chronic back pain. Back pain has
      also emerged as the strongest predictor of major depression. Assessing and
      treating patients in a manner that integrates psychosocial and biological aspects
      of care is the essence of excellent family medicine. This case illustrates the
      importance for primary care physicians of screening for depression and other
      psychosocial factors in assessing patients with persistent back pain.

PMID- 22477949
TI  - Post-partum depression: a comprehensive approach to evaluation and treatment.
AB  - Post-partum depression (PPD) presents a significant disruption to the mother
      infant relationship. Such disruptions are associated with risks to the
      neurological, socio-emotional and cognitive functioning of the developing infant.
      A review of this literature supports the early detection of PPD and the
      application of comprehensive, psychotherapeutic interventions that target the
      functioning of the infant, the mother and the mother-infant relationship.
      Ecological factors important to evaluation and avenues of intervention are
      emphasised. The need for further research to determine evidence-based methods of
      intervention is described.

PMID- 22477951
TI  - The midwestern association of behavior analysis: Past, present, future.

PMID- 22477948
TI  - Perinatal depression: implications for child mental health.
AB  - Perinatal depression is common and primary care holds a crucial role for
      detecting, treating or, if necessary, providing referrals to mental health care
      for affected women. Family doctors should be aware of risk factors for peripartum
      depression, including previous history of depression, life events and
      interpersonal conflict. Perinatal depression has been associated with many poor
      outcomes, including maternal, child and family unit challenges. Infants and young
      children of perinatally depressed mothers are more likely to have a difficult
      temperament, as well as cognitive and emotional delays. The primary care setting
      is uniquely poised to be the screening and treatment site for perinatal
      depression; however, several obstacles, both at patient and systems level, have
      been identified that interfere with women's treatment engagement. Current
      published treatment guidelines favour psychotherapy above medicines as first line
      treatment for mild to moderate perinatal depression, while pharmacotherapy is
      first choice for severe depression, often in combination with psychosocial or
      integrative approaches. Among mothers who decide to stop taking their
      antidepressants despite ongoing depression during the perinatal period, the
      majority suffer from relapsing symptoms. If depression continues post-partum,
      there is an increased risk of poor mother-infant attachment, delayed cognitive
      and linguistic skills in the infant, impaired emotional development and risk for
      behavioural problems in later life. Complex, comprehensive and multilevel
      algorithms are warranted to treat perinatal depression. Primary care doctors are
      best suited to initiate, carry out and evaluate the effectiveness of such
      interventions designed to prevent adverse outcomes of maternal perinatal
      depression on mother and child wellbeing.

PMID- 22477950
TI  - Editorial.

PMID- 22477952
TI  - A behavioral approach to the teaching of composition.

PMID- 22477953
TI  - Theory and technology in behavior analysis.
AB  - The differences within behaviorism in general and behavior analysis in particular
      have been described in many ways. Some of the more common distinctions are "basic
      versus applied", "clinical versus non-clinical", "behavior therapy versus
      behavior analysis", and "experimental analysis of behavior versus applied
      behavior analysis". These and other such distinctions do not seem to refer to
      truely important differences, or refer to important differences in confusing
      ways. It is suggested that there are two main dimensions which divide
      behaviorists into meaningful units: the type of paradigm (behavior analysis
      versus methodological behaviorism) and the level of analysis (technical,
      methodological, conceptual, or philosophical). By considering these two
      dimensions a number of issues in the field are recast. In particular, many of the
      differences within behavior analysis are recast into questions of the
      relationship between theory and technology.

PMID- 22477954
TI  - Engineering environments for behavioral opportunities in the zoo.

PMID- 22477955
TI  - Instructional technology and educational reform: 1977.

PMID- 22477956
TI  - A behavior-analytic critique of Bandura's self-efficacy theory.
AB  - A behavior-analytic critique of self-efficacy theory is presented. Self-efficacy
      theory asserts that efficacy expectations determine approach behavior and
      physiological arousal of phobics as well as numerous other clinically important
      behaviors. Evidence which is purported to support this assertion is reviewed. The
      evidence consists of correlations between self-efficacy ratings and other
      behaviors. Such response-response relationships do not unequivocally establish
      that one response causes another. A behavior-analytic alternative to self
      efficacy theory explains these relationships in terms of environmental events.
      Correlations between self-efficacy rating behavior and other behavior may be due
      to the contingencies of reinforcement that establish a correspondence between
      such verbal predictions and the behavior to which they refer. Such a behavior
      analytic account does not deny any of the empirical relationships presented in
      support of self-efficacy theory, but it points to environmental variables that
      could account for those relationships and that could be manipulated in the
      interest of developing more effective treatment procedures.

PMID- 22477957
TI  - Three conceptual units for behavior.
AB  - THREE GENERIC UNITS FOR BEHAVIOR ARE EXAMINED IN TERMS OF THEIR BACKGROUND: an if
      then unit for stimulus and response (S-R), a holistic unit for Kantor's behavior
      segment, and an AB-because-of-C unit for Skinner's three-term contingency. The
      units are distinguished in terms of their respective historical backgrounds,
      causal modes, advantages, and disadvantages. The ways in which these units may be
      compatible are discussed.

PMID- 22477958
TI  - A history of the term radical behaviorism: From Watson to Skinner.
AB  - This paper describes the origins and evolution of the term radical behaviorism.
      John B. Watson's coining of behaviorism in 1913 is presented first, followed by a
      discussion of the uses of "radical" within psychology during these early years.
      When the term radical behaviorism first emerged in the early 1920s, its referent
      was Watson's behaviorism, most specifically his stance on consciousness. In the
      1930s, B. F. Skinner described his own position with the term radical behaviorism
      in an unpublished manuscript, and then in 1945 first referred in print to his
      views as such. Today, radical behaviorism is generally applied to Skinner's views
      alone. The paper concludes with a brief discussion of a similarity in Watson's
      and Skinner's positions on consciousness, which seems a possible historical and
      philosophical connection between their respective radical behaviorisms.

PMID- 22477959
TI  - Function-altering effects of contingency-specifying stimuli.
AB  - Contingengy-specifying stimuli (CSSs) can function differently than
      discriminative stimuli. Rather than evoking behavior due to a history of
      discrimination training, they alter the function of other stimuli and, therefore,
      the behavioral relations involving those stimuli. CSSs can alter the evocative
      function of discriminative stimuli, establishing operations, and conditional
      stimuli, as well as the efficacy of reinforcing and punishing stimuli and of
      stimuli that can function in second-order respondent conditioning. The concept of
      function-altering CSSs has implications for such areas of interest as stimulus
      equivalence, the terminology involving "rules" and "rule-governed behavior," and
      the way in which behavior analysts view the effects of such basic processes as
      reinforcement and punishment.

PMID- 22477960
TI  - Quantitative order in B. F. Skinner's early research program, 1928-1931.
AB  - The purpose of this article is to provide a coherent story of Skinner's graduate
      school (1928-1931) research projects, adding to Skinner's own accounts a
      different emphasis and a number of interesting details. The story is guided by
      the proposal that a search for quantitative order was the "unifying force" amid
      the variety of apparatus changes and shifts of research topic in Skinner's early
      development as a researcher. Archival laboratory-research records from several
      apparatuses which Skinner constructed between 1928 and 1931 (1) indicate that his
      research program was more complicated than he has implied; (2) show that he
      worked on three interdependent lines of investigation simultaneously; (3) suggest
      that change or abandonment of an apparatus or a project was markedly affected by
      his success (and failure) in his primary objective, which was to find
      quantitative orderliness in measured behavior. Frequent apparatus change in the
      period of 1928 to 1930 ceased when he obtained quantitative orderliness in the
      panel-press and lever-box preparations. In the examination of archival records,
      questions about the enterprise of biographical understanding are considered.

PMID- 22477961
TI  - Introductory comments.

PMID- 22477962
TI  - Crime prevention through social and physical environmental change.
AB  - One approach to crime prevention where behavior analysts can make important
      contributions is the modification of environmental opportunities and victim
      vulnerabilities that are related to higher rates of offending. Examples of
      environmental crime prevention are discussed in the following areas: (1)
      modifying physical environments in order to "harden" targets of crime, (2)
      training victims to be less vulnerable to victimization, (3) eliminating
      portrayals of certain groups of people that legitimize their victimization, and
      (4) organizing neighborhoods and communities to strengthen their means of social
      control. Two implications of environmental crime prevention-the role of
      individual differences and the scope of prevention-are discussed.

PMID- 22477963
TI  - Delinquency prevention through training parents in family management.
AB  - Nearly two decades of clinical research at the Oregon Social Learning Center
      (OSLC) have helped to shape a theory of antisocial behavior in boys. Models
      depicting the theory are presented and discussed. In addition, family management
      variables such as "discipline," "monitoring," "positive parenting," and "problem
      solving" are described as used in clinical applications. Total aversive behavior
      (TAB), based on home observations, and parent daily report (PDR), based on
      telephone interviews, are examined as outcome indicators for a variety of studies
      investigating the efficacy of the OSLC social interactional therapy. Several
      recent reports of treatment for adjudicated adolescents and their families are
      included; law violations are the dependent measures in those studies. Examples of
      the interface between clinical work and theory at OSLC are presented. Questions
      of generalization of the clinical methodology to large urban populations, and
      access to parents who most need to learn the parenting techniques are noted.

PMID- 22477964
TI  - Social policy and the role of the behavior analyst in the prevention of
      delinquent behavior.
AB  - The purpose of this article is to encourage behavior analysts to expand their
      domain of interest and application to include the "social/political"
      contingencies that are developed and implemented by policymakers and lawmakers.
      Using the Vermont juvenile justice system as a prototype, examples are provided
      that focus on the tertiary, secondary, and primary prevention of delinquent
      behavior.

PMID- 22477965
TI  - Misdescribing the carneau: A perplexing plurality.

PMID- 22477966
TI  - When we speak of integrating..

PMID- 22477967
TI  - The great power of steady misrepresentation: Behaviorism's presumed denial of
      instinct.

PMID- 22477968
TI  - "Separate disciplines" is another name for survival.

PMID- 22477969
TI  - The cultural mission of behaviorology.

PMID- 22477970
TI  - The debate about praxics: Some comments meant especially for students.

PMID- 22477972
TI  - Editorial.

PMID- 22477971
TI  - The trend of stimulus control publications.

PMID- 22477973
TI  - Walden two: The morality of anarchy.
AB  - The utopian label is often pinned on calls for comprehensive change as a means of
      dismissing them from serious consideration.... [S]ocial orders come and go, and
      those who indulge in utopian thinking may be more prepared for... the
      inevitability of widespread societal transformation.... Keeping utopia in mind
      can prevent our settling for minor reforms when more significant change might be
      possible. (Fox, 1985, p. 55)When... I called myself a benign anarchist... someone
      said that that was not like the dictatorship of Walden Two. But Walden Two was
      anarchistic.... The functions delegated to [authority figures] in the world at
      large were performed by the people themselves through face-to-face commendation
      and censure. (Skinner, 1983, p. 426, emphasis his)The issue for anarchists is not
      whether there should be structure or order, but what kind there should be and
      what its sources ought to be. The individual or group which has sufficient
      liberty to be self-regulating will have the highest degree of order; the
      imposition of order from above and outside induces resentment and rebellion where
      it does not encourage childlike dependence and impotence, and so becomes a force
      for disorder. (Barclay, 1982, p. 17).

PMID- 22477974
TI  - Theoretical implications of the neurotic paradox as a problem in behavior theory:
      An experimental resolution.
AB  - Why do human phobias last for months or years when such behavior should undergo
      extinction? This failure of extinction or persistence of self-defeating behavior
      of human disorders was labeled by Mowrer as the neurotic paradox. The paradox is
      cited by an ever-increasing number of critics who challenge any laboratory-based
      learning model of human psychopathology. Laboratory research, of course, omits
      essential requirements in the analysis of behavior, and the principles derived
      from such analyses must be combined in order to explain complex human behavaior.
      Validation for a behavioral model can thus be achieved if (a) basic principles
      inferred from observation of humans treated with a laboratory-derived extinction
      procedure (e.g., implosive therapy) are combined with (b) principles examined in
      laboratory research that are combined to generate unique predictions that
      correspond to known features of human phobic behavior. The latter evidence is
      briefly reviewed in research demonstrating sustained responding over one thousand
      consecutive active avoidance responses with complete avoidance of the "phobic" CS
      for an initial single shock trial. Differential reinforcement for responses to
      early sequential stimuli depends on minimal work requirement, and reinforcement
      by timeout from avoidance. This combination of factors effectively precludes
      extinction to main conditioned aversive stimuli for nonhumans, as it does for
      human phobias. Support for a laboratory model of human phobia is thereby
      attained.

PMID- 22477975
TI  - On the virtues of being a psychologist.
AB  - Some changes that have taken place in psychology are discussed in the light of
      the presently urgent need for a new science of psychology that addresses the
      important social issues of our times. Substantial development of the experimental
      analysis of behavior is urged, through its formulation of research problems
      related to every aspect of contemporary life, extending from political
      negotiation and economic decision making to the study of personality and
      individual differences.

PMID- 22477976
TI  - Rules: Function-altering contingency-specifying stimuli.
AB  - Behavior analysts have traditionally defined rules as discriminative stimuli.
      Three problems with this interpretation are discussed. First, because the effects
      of rules are often delayed, and the effects of discriminative stimuli are
      immediate, classifying rules as discriminative stimuli violates the definitional
      requirements of the latter. Second, when rules are defined as discriminative
      stimuli, other truly unique effects of rules may be obscured. Finally, both rules
      and contingencies develop new behavioral relations; however, when rules are
      interpreted as discriminative stimuli, their effects are not readily compared
      with those of contingencies. As an alternative, we suggest that rules be
      interpreted as function-altering contingency-specifying stimuli. Implications of
      this function-altering interpretation for terminology and research strategy are
      discussed.

PMID- 22477977
TI  - Reinforcement in the sixteenth century: Was the bard a behaviorist?
AB  - Shakespeare's play The Taming of the Shrew is described in terms of behavior
      analysis. Changes in the behavior of the character Kate result from her husband
      Petruchio's manipulation of environmental contingencies. Aspects of behavior
      analysis found in the play include the identification of target behavior, the
      establishment of events as reinforcers, the arrangement of contigencies between
      responses and reinforcers, and the assessment of post-intervention responding.
      Several aspects of Shakespeare's description are related to current issues in
      behavior analysis bearing on theory, cultural practices, and public relations.

PMID- 22477978
TI  - Inversion of the three-term contingency.

PMID- 22477979
TI  - Developing behavior analysis at the state level.
AB  - Over the past fifteen years, behavior analysts in Florida have worked together to
      develop the discipline with a multifaceted system of contingencies. Basing their
      effort in the area of retardation and with the cooperation of the state's
      Developmental Services Program Office, they have gradually developed a regulatory
      manual of programming policy and procedures, a hierarchical system of
      responsibilities for programming approval and monitoring, a state-sponsored
      certification program, a professional association, and an active university
      community. These components are described and discussed in terms of suggested
      principles for developing the field of behavior analysis within a state.

PMID- 22477981
TI  - The ABA humanitarian award: Introduction of the presenter.

PMID- 22477980
TI  - The ABA humanitarian awards for outstanding achievement in pursuit of the right
      to effective treatment.

PMID- 22477982
TI  - The ABA humanitarian awards for the right to effective treatment: Presentations
      to Robert A. Sherman and Claudia and Leo Soucy.

PMID- 22477983
TI  - The concept of consequences in the analysis of behavior.

PMID- 22477984
TI  - In response to Axelrod's review of alternatives to punishment.

PMID- 22477985
TI  - "Look homeward angel": A call to return to our (Functional) roots.

PMID- 22477986
TI  - In response to Kohler and Greenwood's "Toward a technology of generalization".

PMID- 22477987
TI  - Rhetoric and cliche: A response to Neitzel and Milich's review of crime and human
      nature.

PMID- 22477988
TI  - Instincts-who needs them?

PMID- 22477989
TI  - Strategic and tactical limits of comparison studies.
AB  - A comparison study is an experiment whose primary purpose is to compare directly
      (regardless of experimental design) at least two different procedures for
      changing behavior or two or more components of such a procedure. This paper
      argues that, in spite of their popularity, such studies typically lead to
      inappropriate inferences with poor generality based on improper evidence gathered
      in support of the wrong question, thus wasting the limited experimental
      resources. The discussion considers problems concerning the functions of
      comparison studies, the nature of the comparisons that are attempted, the
      generality of their findings, and the limited role that they can play in
      technological research.

PMID- 22477990
TI  - Task force on behavior analysis and public policy: Executive council liaison
      commentary.

PMID- 22477992
TI  - Recommendations of the task force on public policy.

PMID- 22477991
TI  - Behavior analysis and public policy.
AB  - The Task Force on Public Policy was created to examine ways for behavior analysts
      to be more functional citizen scientists in the policymaking arena. This report
      informs readers about the contexts and processes of policymaking; and it outlines
      issues regarding the roles of behavior analysts in crating policy-relevant
      conceptual analyses, generating research data, and communicating policy-relevant
      information. We also discuss a possible role for the professional association in
      enhancing analysis, research, and advocacy on policies relevant to the public
      interest.

PMID- 22477993
TI  - August Dvorak (1894-1975): Early expressions of applied behavior analysis and
      precision teaching.
AB  - August Dvorak is best known for his development of the Dvorak keyboard. However,
      Dvorak also adapted and applied many behavioral and scientific management
      techniques to the field of education. Taken collectively, these techniques are
      representative of many of the procedures currently used in applied behavior
      analysis, in general, and especially in precision teaching. The failure to
      consider Dvorak's instructional methods may explain some of the discrepant
      findings in studies which compare the efficiency of the Dvorak to the standard
      keyboard. This article presents a brief background on the development of the
      standard (QWERTY) and Dvorak keyboards, describes parallels between Dvorak's
      teaching procedures and those used in precision teaching, reviews some of the
      comparative research on the Dvorak keyboard, and suggests some implications for
      further research in applying the principles of behavior analysis.

PMID- 22477994
TI  - Laboratory lore and research practices in the experimental analysis of human
      behavior.
AB  - Growing interest in experimental analyses of human behavior has augmented the
      importance of describing its "laboratory lore" and research practices.
      "Laboratory lore" refers to the informal and miscellaneous collection of facts,
      assumptions, and techniques regarding the conduct of experimental research. This
      series of papers describes the laboratory lore and research practices of
      experimental analysts of human behavior. Topics include selecting subjects,
      designing session logistics, developing instructions, selecting reinforcers, and
      using subjects' verbal reports. These descriptions are offered as a step toward
      developing improved procedures for conducting research with human subjects.

PMID- 22477995
TI  - Laboratory lore and research practices in the experimental analysis of human
      behavior: Subject selection.

PMID- 22477996
TI  - Laboratory lore and research practices in the experimental analysis of human
      behavior: Designing session logistics-how long, how often, how many?

PMID- 22477997
TI  - Laboratory lore and research practices in the experimental analysis of human
      behavior: Issues in instructing subjects.

PMID- 22477998
TI  - Laboratory lore and research practices in the experimental analysis of human
      behavior: Selecting reinforcers and arranging contingencies.

PMID- 22477999
TI  - Laboratory lore and research practices in the experimental analysis of human
      behavior: Use and abuse of subjects' verbal reports.

PMID- 22478000
TI  - The sorcerer's apprentice: A review of Hardy's behavior analysis: A computer
      based tutorial.

PMID- 22478001
TI  - Radical behaviorism: A nonradical recommendation.

PMID- 22478002
TI  - Editorial.

PMID- 22478003
TI  - Matching theory in natural human environments.
AB  - Matching theory is a mathematical account of behavior, many aspects of which have
      been confirmed in laboratory experiments with nonhuman and human subjects. The
      theory asserts that behavior is distributed across concurrently available
      response alternatives in the same proportion that reinforcement is distributed
      across those alternatives. The theory also asserts that behavior on a single
      response alternative is a function not only of reinforcement contingent on that
      behavior, but also of reinforcement contingent on other behaviors and of
      reinforcement delivered independently of behavior. These assertions constitute
      important advances in our understanding of the effects of reinforcement on
      behavior. Evidence from the applied literature suggests that matching theory
      holds not only in laboratory environments, but also in natural human
      environments. In addition, the theory has important therapeutic implications. For
      example, it suggests four new intervention strategies, and it can be used to
      improve treatment planning and management. Research on matching theory
      illustrates the progression from laboratory experimentation with nonhuman
      subjects to therapeutic applications in natural human environments.

PMID- 22478004
TI  - Task force on the right to effective treatment: Executive council liaison
      commentary.

PMID- 22478005
TI  - The right to effective behavioral treatment.
AB  - WE PROPOSE THAT INDIVIDUALS WHO ARE RECIPIENTS OR POTENTIAL RECIPIENTS OF
      TREATMENT DESIGNED TO CHANGE THEIR BEHAVIOR HAVE THE RIGHT TO: (1) a therapeutic
      environment, (2) services whose overriding goal is personal welfare, (3)
      treatment by a competent behavior analyst, (4) programs that teach functional
      skills, (5) behavioral assessment and ongoing evaluation, and (6) the most
      effective treatment procedures available.

PMID- 22478006
TI  - Toward an explicit analysis of generalization: A stimulus control interpretation.
AB  - Producing generality of treatment effects to new settings has been a critical
      concern for applied behavior analysts, but a systematic and reliable means of
      producing generality has yet to be provided. We argue that the principles of
      stimulus control and reinforcement underlie the production of most generalized
      effects; therefore, we suggest interpreting generalization programming in terms
      of stimulus control. The generalization programming procedures identified by
      Stokes and Baer (1977) are discussed in terms of both the stimulus control
      tactics explicitly identified and those that may be operating but are not
      explicitly identified. Our interpretation clarifies the critical components of
      Stokes and Baer's procedures and places greater emphasis on planning for
      generalization as a part of training procedures.

PMID- 22478007
TI  - The virtues of scientific psychology: A reply to Harzem.
AB  - Harzem recently expressed the opinions that, beginning in the 1960s, the progress
      of scientific psychology has been deferred and that psychological research has
      failed to address important social issues. He proposed that progress be resumed
      by taking up, anew, the experimental analysis of behavior. The present reply
      provides evidence inconsistent with Harzem's assertions regarding the state of
      contemporary, scientific psychology and questions the wisdom of disregarding the
      significant body of data and theory that currently are available to pursue the,
      as yet, unfulfilled promises of the experimental analysis of human behavior.

PMID- 22478008
TI  - Behavioral obesity research: Where have all the single subjects gone?
AB  - Many recent reviews of the literature concerning behavioral treatments of obesity
      have concluded that behavioral methods have not been as successful in treating
      this problem as might have been predicted in the early years of behavior
      modification. Among the many potential reasons for this lack of success is the
      growing trend to utilize group statistical designs rather than single subject
      designs to examine the problem of obesity, in spite of the fact that single case
      methodology has provided the foundation for applied behavior analysis and
      behavior therapy. Several behavioral journals were surveyed to determine more
      precisely the trends in types of research strategies utilized in obesity studies.
      The potential relationship between research methodology and the development of
      effective treatments is discussed.

PMID- 22478009
TI  - The development and adoption of controversial default technologies.
AB  - Default technologies evolve from failure. Within the realm of human behavior,
      technologies based on the use of aversive contingencies can be conceptualized as
      default technologies because they come into play when natural contingencies or
      positive reinforcement fail to produce a desired behavioral outcome. Historical
      as well as contemporary events suggest that it is a mistake for behavior analysts
      to advocate for the adoption of aversive technologies. We must, however, continue
      to play a leading role in the development of such technologies so that they will
      be used in an appropriate manner. Furthermore, the eventual elimination of
      aversive technologies will be possible only through continued, careful, and
      experimental analysis of the contexts of failure in which they are born.

PMID- 22478010
TI  - Introductory comments.

PMID- 22478011
TI  - Contingencies and metacontingencies: Toward a synthesis of behavior analysis and
      cultural materialism.
AB  - A synthesis of cultural materialism and behavior analysis might increase the
      scientific and technological value of both fields. Conceptual and substantive
      relations between the two fields show important similarities, particularly with
      regard to the causal role of the environment in behavioral and cultural
      evolution. Key concepts in Marvin Harris's cultural materialist theories are
      outlined. A distinction is made between contingencies at the behavioral level of
      analysis (contingencies of reinforcement) and contingencies at the cultural level
      of analysis (metacontingencies). Relations between the two kinds of contingencies
      are explored in cultural practices from paleolithic to industrial sociocultural
      systems. A synthesis of these two fields may offer the opportunity to resolve
      serious problems currently facing modern cultures.

PMID- 22478012
TI  - Rule-governed behavior and behavioral anthropology.
AB  - According to cultural materialism, cultural practices result from the
      materialistic outcomes of those practices, not from sociobiological, mentalistic,
      or mystical predispositions (e.g., Hindus worship cows because, in the long run,
      that worship results in more food, not less food). However, according to behavior
      analysis, such materialistic outcomes do not reinforce or punish the cultural
      practices, because such outcomes are too delayed, too improbable, or individually
      too small to directly reinforce or punish the cultural practices (e.g., the food
      increase is too delayed to reinforce the cow worship). Therefore, the molar,
      materialistic contingencies need the support of molecular, behavioral
      contingencies. And according to the present theory of rule-governed behavior, the
      statement of rules describing those molar, materialistic contingencies can
      establish the needed molecular contingencies. Given the proper behavioral
      history, such rule statements combine with noncompliance to produce a learned
      aversive condition (often labeled fear, anxiety, or guilt). The termination of
      this aversive condition reinforces compliance, just as its presentation punishes
      noncompliance (e.g., the termination of guilt reinforces the tending to a sick
      cow). In addition, supernatural rules often supplement these materialistic rules.
      Furthermore, the production of both materialistic and supernatural rules needs
      cultural designers who understand the molar, materialistic contingencies.

PMID- 22478013
TI  - The detrimental effects of extrinsic reinforcement on "Intrinsic motivation".
AB  - Extrinsic consequences have been criticized on the grounds that they decrease
      intrinsic motivation or internally initiated behavior. Two popular rationales for
      this criticism, Lepper's overjustification hypothesis (1981) and Deci's
      motivational theory (Deci & Ryan, 1985), are reviewed and the criticism is then
      redefined behaviorally. "Intrinsically controlled" behavior is defined as
      behavior maintained by response-produced reinforcers, and the question concerning
      extrinsic consequences is thus restated as follows: When behavior is maintained
      by response-produced stimuli, does extrinsic reinforcement decrease the
      reinforcing value of those stimuli? The empirical support for this detrimental
      effect is summarized briefly, and several possible explanations for the
      phenomenon are offered. Research results that reflect on the effect's generality
      and social significance are discussed next, with the conclusion that the effect
      is transient and not likely to occur at all if extrinsic rewards are reinforcing,
      noncompetitive, based on reasonable performance standards, and delivered
      repetitively.

PMID- 22478014
TI  - Behavior analysts and cultural analysis: Troubles and issues.
AB  - THREE STRATEGIC SUGGESTIONS ARE OFFERED TO BEHAVIOR ANALYSTS WHO ARE CONCERNED
      WITH EXTENDING THE INTERESTS OF OUR DISCIPLINE INTO DOMAINS TRADITIONALLY
      ASSIGNED TO THE SOCIAL SCIENCES: (1) to expand our world-view perspectives beyond
      the boundaries commonly accepted by psychologists in general; (2) to build a
      cultural analytic framework upon the foundations we have developed for the study
      of individuals; and (3) to study the works of those social scientists whose views
      are generally compatible with, and complementary to, our own. Sociologist C.
      Wright Mills' distinction between troubles and issues and anthropologist Marvin
      Harris's principles of cultural materialism are related to topics raised by these
      three strategies. The pervasiveness of the "psychocentric" world view within
      psychology and the social sciences, and throughout our culture at large, is
      discussed from the points of view of Skinner, Mills, and Harris. It is suggested
      that a thorough commitment to radical behaviorism, and continuation of
      interaction between radical behaviorism and cultural materialism, are necessary
      for maintaining and extending an issues orientation within the discipline of
      behavior analysis and for guarding against dilutions and subversions of that
      orientation by "deviation-dampening" contingencies that exist in our profession
      and in our culture at large.

PMID- 22478015
TI  - Logic, reasoning, and verbal behavior.
AB  - This paper analyzes the traditional concepts of logic and reasoning from the
      perspective of radical behaviorism and in the terms of Skinner's treatment of
      verbal behavior. The topics covered in this analysis include the proposition,
      premises and conclusions, logicality and rules, and deductive and inductive
      reasoning.

PMID- 22478017
TI  - Misconstruing behavioral consequences: Teleology or teleonomy.

PMID- 22478016
TI  - Some historical relationships between science and technology with implications
      for behavior analysis.
AB  - The relationship between science and technology is examined in terms of some
      implications for behavior analysis. Problems result when this relationship is
      seen as one in which science generally begets technology in a one-way, or
      hierarchical, relationship. These problems are not found when the relationship
      between science and technology is seen as two-way, or symmetrical, within a
      larger context of relationships. Some historical examples are presented.
      Collectively, these and other examples in the references weaken the case for a
      prevailing one-way, hierarchical relationship and strengthen the case for a two
      way, symmetrical relationship. In addition to being more accurate historically,
      the symmetrical relationship is also more consistent with the principles of
      behavior analysis.

PMID- 22478018
TI  - Comments about the isolation of behavior analysis.

PMID- 22478019
TI  - Social work: Professional opportunities for behavior analysts.

PMID- 22478021
TI  - Social validity and the report of the ABA task force on right to effective
      treatment.

PMID- 22478020
TI  - The future of radical behaviorism: Brief comments on Glenn's editorial and
      Drash's "On terms".

PMID- 22478022
TI  - The influence of behavior analysis on the surgeon general's report, the health
      consequences of smoking: Nicotine addiction.

PMID- 22478023
TI  - A reply to Graf's review of Hardy's behavior analysis: A computer-based tutorial.

PMID- 22478024
TI  - Editorial.

PMID- 22478025
TI  - A lost art.

PMID- 22478026
TI  - The road less traveled by.

PMID- 22478027
TI  - The convergence of behavioral biology and operant psychology: Toward an
      interlevel and interfield science.
AB  - Behavioral biology and operant psychology have developed in parallel but separate
      paths since their origins in the 1930s. In the first three decades, both fields
      dealt with microscopic (or molecular) controlling variables and qualitative data.
      Since about 1960, both have primarily focused on macroscopic (or molar)
      controlling variables. Their shared interest in foraging in the 1980s suggests a
      limited convergence beween biologists and psychologists in data, methods, and
      theories. We draw on accounts of intertheoretic relations from the philosophy of
      science, including both interlevel theory and interfield theory, to understand
      this convergence. However, our greater emphasis on methods of data collection and
      analysis leads us to characterize the convergence as not only one of interfield
      theory but one of interfield science.

PMID- 22478028
TI  - Some remarks on the quantitative analysis of behavior.
AB  - This paper discusses similarities between the mathematization of operant behavior
      and the early history of the most mathematical of sciences-physics. Galileo
      explored the properties of motion without dealing with the causes of motion,
      focusing on changes in motion. Newton's dynamics were concerned with the action
      of forces as causes of change. Skinner's rationale for using rate to describe
      behavior derived from an interest in changes in rate. Reinforcement has played
      the role of force in the dynamics of behavior. Behavioral momentum and
      maximization have received mathematical formulations in behavior analysis. Yet to
      be worked out are the relations between molar and molecular formulations of
      behavioral theory.

PMID- 22478029
TI  - Two modern developments in matching theory.
AB  - Matching theory is a mathematical theory of choice behavior, parts of which have
      been shown to hold in natural human environments and to have important
      therapeutic applications. Two modern developments in matching theory are
      discussed in this article. The first is the mathematical description of behavior
      in asymmetrical choice situations, which are situations where different
      reinforcers and/or different behaviors are associated with concurrently available
      response alternatives. Most choice situations in natural human environments are
      probably asymmetrical. The second development in matching theory is the
      mathematical description of a tendency toward indifferent responding in all
      choice situations. Behavior in asymmetrical choice situations and the tendency
      toward indifferent responding in all choice situations can be described by
      modifications of the matching equations, which change the equations from lines
      into power functions. These modern forms have been extraordinarily successful in
      describing behavior in choice situations, and are the forms most likely to
      accurately describe human behavior in naturally occurring environments.

PMID- 22478030
TI  - Quantitative prediction and molar description of the environment.
AB  - Molecular explanations of behavior, based on momentary events and variables that
      can be measured each time an event occurs, can be contrasted with molar
      explanations, based on aggregates of events and variables that can be measured
      only over substantial periods of time. Molecular analyses cannot suffice for
      quantitative accounts of behavior, because the historical variables that
      determine behavior are inevitably molar. When molecular explanations are
      attempted, they always depend on hypothetical constructs that stand as surrogates
      for molar environmental variables. These constructs allow no quantitative
      predictions when they are vague, and when they are made precise, they become
      superfluous, because they can be replaced with molar measures. In contrast to
      molecular accounts of phenomena like higher responding on ratio schedules than
      interval schedules and free-operant avoidance, molar accounts tend to be simple
      and straightforward. Molar theory incorporates the notion that behavior produces
      consequences that in turn affect the behavior, the notion that behavior and
      environment together constitute a feedback system. A feedback function specifies
      the dependence of consequences on behavior, thereby describing properties of the
      environment. Feedback functions can be derived for simple schedules, complex
      schedules, and natural resources. A complete theory of behavior requires
      describing the environment's feedback functions and the organism's functional
      relations. Molar thinking, both in the laboratory and in the field, can allow
      quantitative prediction, the mark of a mature science.

PMID- 22478031
TI  - Describing behavior with ratios of count and time.
AB  - Describing behavior with ratios of count and time is a popular measurement tactic
      in the field of behavior analysis. The paper examines some count and time ratios
      in order to determine what about behavior each describes and why one ratio may
      sometimes be more useful than another. In addition, the paper briefly considers
      some terminological issues, derived quantities, dimensional analysis, some
      advantages and disadvantages of ratios, and selection of useful quantities for
      measurement.

PMID- 22478032
TI  - Avoidance at columbia.

PMID- 22478033
TI  - Time past, time present, time future.

PMID- 22478034
TI  - Concerning the hallmark of a discrimination.

PMID- 22478035
TI  - Keller and Schoenfeld's principles of psychology.

PMID- 22478036
TI  - Keller, Schoenfeld, Cumming, and Berryman as instructional stimuli.

PMID- 22478037
TI  - A reply to Kent-Udolf's review of behavior analysis language instrument and
      behavior analysis language program.

PMID- 22478038
TI  - Rats.

PMID- 22478039
TI  - What is unnatural about "Extrinsic reinforcement?".

PMID- 22478040
TI  - Editorial.

PMID- 22478042
TI  - Dimension in action: A commentary on Powell and Dickie.

PMID- 22478041
TI  - Kinetic output: A conceptual, dimensional and empirical analysis.
AB  - A dimensional analysis permitted behavioral frequency, duration and available
      time to be collapsed into a singular dimensionless expression called Kinetic
      output (K(o)). An empirical analysis across several behaviors in some human
      subjects showed that the derived index of behavioral output, K(o), was more
      likely to exhibit less variability than rate or duration measures of the
      behavior. As a reduction in variability is synonymous with finding an increased
      order, the results tentatively support the notion that behavior may exhibit
      conformity at a previously undetected level. One major implication of the K(o)
      formulation is that divergent frequency and duration performances are
      interpretable as reflecting alternate forms of the same equivalence.

PMID- 22478043
TI  - Behavior measures and variability.

PMID- 22478044
TI  - Total duration weighted by frequency: A meaningful measure?

PMID- 22478046
TI  - Separating the wheat from the chaff: A review of some commentaries concerning the
      conceptual and empirical status of kinetic output.

PMID- 22478045
TI  - Describing behavioral variability.

PMID- 22478047
TI  - Forgetting the lessons of history.
AB  - While a great deal of behavior analytic research has focussed on studying current
      contingencies, the amount of work done in the area of conditioning history is
      spotty, at best. Weiner (1964, 1969) conducted history research with human
      subjects, but little has followed in either the human or the nonhuman literature.
      Some direction can also be found in the literature studying the effects of
      conditioning on drug effects (e.g., Barrett, 1977; Urbain, Poling, Millam, &
      Thompson, 1978). However, "behavioral history" or "conditioning history" has not
      been a fully-developed area within behavior analysis. It is suggested that
      empirical work on history effects might have implications for (a) better
      understanding human-nonhuman behavioral differences and similarities, (b)
      clinical applications, especially where clients are resistant to behavioral
      change, and (c) theoretical assumptions in behavior analysis in relation to both
      basic and applied concerns.

PMID- 22478048
TI  - Overcorrection: Reviewed, revisited and revised.
AB  - Overcorrection is a widely used behavior management procedure, the success of
      which has been well documented. However, overcorrection is not a simple, single
      procedure. Rather, it is a complex combination of procedures that often make it a
      complicated strategy to understand conceptually and to implement correctly. The
      complex nature of overcorrection combined with the use of multiple labels has
      created much confusion and debate among both researchers and practitioners. A
      number of issues relating to overcorrection are examined and evaluated. A
      proposal is made for revising the present overcorrection terminology. Finally,
      directions for future research are suggested.

PMID- 22478049
TI  - Reflections on the impact of K & S as a systematic textbook.

PMID- 22478050
TI  - Control of contingencies of reinforcement in the laboratory.

PMID- 22478051
TI  - PSI: Two unorthodox studies.

PMID- 22478052
TI  - Past imperfect, present conditional: Some research on formative evaluation.

PMID- 22478053
TI  - He met the challenge of technology transfer.

PMID- 22478054
TI  - Ontological and ideological commitments in behavior analysis.

PMID- 22478055
TI  - Methodological commitments and other philosophic necessities.

PMID- 22478056
TI  - Suggested North American translations of behavior analytic and operant
      conditioning terms.

PMID- 22478057
TI  - Reflections on B. F. Skinner.

PMID- 22478058
TI  - To know the future.

PMID- 22478059
TI  - A procedural analysis of correspondence training techniques.
AB  - A variety of names have been given to procedures used in correspondence training,
      some more descriptive than others. In this article I argue that a terminology
      more accurately describing actual procedures, rather than the conceptual function
      that those procedures are assumed to serve, would benefit the area of
      correspondence training. I identify two documented procedures during the
      reinforcement of verbalization phase and five procedures during the reinforcement
      of correspondence phase and suggest that those procedures can be classified, or
      grouped into nonoverlapping categories, by specifying the critical dimensions of
      those procedures belonging to a single category. I suggest that the names of such
      nonoverlapping categories should clearly specify the dimensions on which the
      classification is based in order to facilitate experimental comparison of
      procedures, and to be able to recognize when a new procedure (as opposed to a
      variant of one already in existence) is developed. Future research involving
      comparative analysis across and within procedures is discussed within the
      framework of the proposed classification.

PMID- 22478060
TI  - What is happening in psychology of learning courses?
AB  - Current practices in the undergraduate Psychology of Learning course were
      assessed through a survey in which a questionnaire probing the teaching of the
      course was sent to 238 4-year colleges and universities in the United States.
      Fifty-four percent of the questionnaires were returned. Learning courses were
      taught at all but 10 of the schools that responded. The course typically is one
      of several that can be selected to fulfill requirements for the major in
      psychology. The course orientation and content varied widely from cognitive to
      eclectic to behavioral, and laboratory requirements existed in less than half of
      the courses. The effects of these practices on behavior analysis are considered
      and several suggestions are made for teaching behavior analysis in the Learning
      course and elsewhere to undergraduates.

PMID- 22478062
TI  - A special section commemorating the 30th anniversary of tactics of scientific
      research: Evaluating experimental data in psychology by Murray Sidman.

PMID- 22478063
TI  - What it means to be a scientist.

PMID- 22478064
TI  - Experimental designs.

PMID- 22478061
TI  - The history of behavior analysis: Some historiography and a bibliography.
AB  - This article has two main purposes. First, it introduces the discipline of
      historiography and, second, it provides a selected bibliography on the history of
      behavior analysis. In introducing the former in the context of the latter, four
      important methodological considerations involved in the process and product of
      historiography are described: The sources from which historical materials are
      drawn (i.e., primary, secondary, and tertiary) and three dimensions along which
      historiography is conducted and evaluated-internalist vs. externalist, great
      person vs. Zeitgeist, and presentist vs. historicist. Integrated throughout are
      four purposes for the historiography of behavior analysis, as well as an overview
      of the topics covered in the extant literature. The manuscript concludes with a
      listing of current bibliographic material by publication type and topic.

PMID- 22478065
TI  - Tactics of scientific research and organizational behavior analysis.

PMID- 22478066
TI  - The "It" that is steady in steady states.

PMID- 22478067
TI  - Tactics of scientific research at 30: Some personal reflections.

PMID- 22478068
TI  - Exploring the controlling conditions of importance.

PMID- 22478069
TI  - Tactics: In reply.

PMID- 22478070
TI  - No longer "Not for professors only".

PMID- 22478071
TI  - The masters thesis in applied behavior analysis: Rationale, characteristics, and
      student advisement strategies.

PMID- 22478072
TI  - Humble behaviorism.

PMID- 22478073
TI  - Humble behaviorism or equal doses of skepticism?

PMID- 22478074
TI  - A post-modern behavior analysis?

PMID- 22478075
TI  - Humble (yet assertive) behaviorism.

PMID- 22478076
TI  - Modesty, yes; Humility, no.

PMID- 22478077
TI  - Irreconcilable differences and political reality in these dark ages.

PMID- 22478078
TI  - Beyond pride and humility.

PMID- 22478079
TI  - Humility, science, and ethological behaviorism.

PMID- 22478080
TI  - Behaviorism: Methodological, radical, assertive, skeptical, ethological, modest,
      humble, and evolving.

PMID- 22478081
TI  - Skinner and Chomsky 30 years later. Or: The return of the repressed.

PMID- 22478082
TI  - The gifts of culture and of eloquence: An open letter to Michael J. Mahoney in
      reply to his article, "Scientific psychology and radical behaviorism".
AB  - In what seems to be a response to a paper by Skinner (1987), Mahoney (1989)
      provides evidence of unfamiliarity with and intellectual intolerance toward
      radical behaviorism by presenting a critique of it that includes a variety of
      improper and counterfactual attributions. For example, he argues that radical
      behaviorism is Cartesian rather than Baconian when the historical record shows
      the opposite, that it is fundamentally associationist when in fact it is
      selectionist, and that its philosophy of science is essentially that of
      operationalism and logical positivism when instead it moved on to other criteria
      decades ago. The details of Mahoney's history are sometimes flawed and sometimes
      unsubstantiated, as when he provides a distorted account of the origins of the
      Association for Behavior Analysis or when he makes undocumented claims about the
      banning of books. On examination, many of his arguments are couched in stylistic
      terms that share their rhetorical features with racial, ethnic, and religious
      stereotyping.

PMID- 22478083
TI  - The enduring intellectual legacy of B. F. Skinner: A citation count from 1966
      1989.
AB  - It is frequently claimed that the influence of behaviorism in general and of B.
      F. Skinner in particular, is declining. Data obtained from the Social Sciences
      Citation Index for the years 1966-1989 document that in the last twenty-four
      years the number of citations to the works of Skinner has been reasonably steady.
      There is no evidence of a decline in the absolute number of such citations,
      suggesting that claims of the demise of behaviorism may be, once again,
      premature.

PMID- 22478084
TI  - Against unifying behaviorism.

PMID- 22478085
TI  - The right to effective education.

PMID- 22478087
TI  - On the difficulty of studying "Basic" behavioral processes in humans.

PMID- 22478086
TI  - Analyzing the reinforcement process at the human level: can application and
      behavioristic interpretation replace laboratory research?
AB  - Critics have questioned the value of human operant conditioning experiments in
      the study of fundamental processes of reinforcement. Contradictory results from
      human and animal experiments have been attributed to the complex social and
      verbal history of the human subject. On these grounds, it has been contended that
      procedures that mimic those conventionally used with animal subjects represent a
      "poor analytic preparation" for the explication of reinforcement principles. In
      defending the use of conventional operant methods for human research, we make
      three points: (a) Historical variables play a critical role in research on
      processes of reinforcement, regardless of whether the subjects are humans or
      animals. (b) Techniques are available for detecting, analyzing, and counteracting
      such historical and extra-experimental influences; these include long-term
      observations, steady state designs, and, when variables are not amenable to
      direct control (e.g., age, gender, species), selection of subjects with common
      characteristics. (c) Other forms of evidence that might be used to validate
      conditioning principles-applied behavior analysis and behavioristic
      interpretation-have inherent limitations and cannot substitute for experimental
      analysis. We conclude that human operant conditioning experiments are essential
      for the analysis of the reinforcement process at the human level, but caution
      that their value depends on the extent to which the traditional methods of the
      experimental analysis of behavior are properly applied.

PMID- 22478088
TI  - Continuity and context.

PMID- 22478089
TI  - The respective roles of human and nonhuman subjects in behavioral research.

PMID- 22478090
TI  - Shared premises, different conclusions.

PMID- 22478091
TI  - Can operant research with animals rescue the science of human behavior?

PMID- 22478092
TI  - Preparations and principles.

PMID- 22478093
TI  - Behavioral history: a promising challenge in explaining and controlling human
      operant behavior.

PMID- 22478094
TI  - The experimental analysis of human behavior: indispensable, ancillary, or
      irrelevant?

PMID- 22478095
TI  - Distressed behavior and its context.
AB  - Behavior that is commonly labeled as indicating distress may have an important
      function in certain clinical problems. Evidence suggests that "distressed"
      behavior is displayed more frequently by persons who are depressed or
      experiencing chronic pain. Such behavior includes nonverbal facial expressions
      and body postures which are typically labeled as "sad," and verbal responses
      involving self-denigration or complaints. Such behaviors appear to form a
      functional response class which has a unique impact on others. The behavior
      appears to be more likely among persons who are receiving aversive stimulation.
      Recipients of distressed behavior are more likely to experience negative emotion,
      yet be solicitous toward the person who displays distressed behavior. Under
      circumstances where distressed behavior is unsuccessful in reducing aversive
      stimulation, the behavior may be shaped and maintained by the fact that it
      temporarily reduces the probability of others behaving aggressively toward the
      person displaying distress. Thus, the development of a pattern of high rates of
      distressed behavior that characterizes clinically depressed persons and persons
      in chronic pain may be partly a result of the unique social contingencies that
      surround this behavior.

PMID- 22478096
TI  - The speciation of behavior analysis.
AB  - The relationship between the Experimental Analysis of Behavior (EAB) and Applied
      Behavior Analysis (ABA) has been the subject of several editorials and
      commentaries in recent years. Various authors have argued that researchers in
      these two fields (a) have become isolated from each other, (b) face different
      requirements for survival in their respective fields, and (c) possess different
      skills to meet those requirements. The present paper provides an allegory for the
      relationship between EAB and ABA in terms of biological speciation. The
      conditions that have changed the relationship between EAB and ABA are parallel to
      those responsible for biological speciation: (a) isolation of some members of a
      species from the rest of the population, (b) different contingencies of survival
      for members of the two separate groups, and (c) divergence in the adaptive
      characteristics displayed by the two groups. When members of two different
      groups, descendants of common ancestors, no longer are capable of producing
      viable offspring by interbreeding, the different groups then represent different
      species. To the extent that members of the EAB group and members of the ABA group
      interact with each other only trivially, they each represent allegorically
      different species. Changes in the relationship between EAB and ABA are part of a
      natural process that takes place in many other sciences, and the course of that
      process can hardly be reversed by us.

PMID- 22478097
TI  - The speciation of behavior analysis: the unnatural selection of foxes and
      hedgehogs.

PMID- 22478098
TI  - What can behavior analysis learn from the aversives controversy?
AB  - The paper argues that behavior analysis may have contributed to the aversives
      controversy in a number of ways. The role that the field has played and the
      lessons that may be learned are discussed in the areas of research, training, and
      politics.

PMID- 22478099
TI  - Aversives, fundamental rights and the courts.

PMID- 22478101
TI  - What's the function of a misnomer?

PMID- 22478100
TI  - "Nonaversive" behavior management: a misnomer.

PMID- 22478102
TI  - Definitions and usage, or a rose by any other name smells as sweet.

PMID- 22478103
TI  - Defining aversiveness: a reply to Van Houten and Salzinger.

PMID- 22478104
TI  - A response to nonaversive behavior management and "Default" technologies.

PMID- 22478105
TI  - Are moral considerations sufficient for selecting nonaversive interventions?: a
      review of Repp and Singh's perspectives on the use of nonaversive and aversive
      interventions for persons with developmental disabilities.

PMID- 22478106
TI  - Should behavior analysts accept Imam's sense of teleology?

PMID- 22478107
TI  - A behavioral perspective on college teaching.
AB  - Much of the subject matter learned in college, particularly during the first two
      years, is taught in relatively large classes with text and lecture as the primary
      source of the information being learned. If students make effective and prolonged
      contact with these sources, they can acquire extensive verbal repertoires in many
      areas of knowledge. Unfortunately there are many other activities that compete
      for the typical student's study time. Several factors are often cited as
      variables that will support study behavior in competition with other activities,
      but the only powerful one available to the teacher is the exam grade, as it is
      related to the course grade. However, unless exams are clearly related to
      appropriate study behavior, require through and extensive coverage of the subject
      matter, occur frequently (preferably no less often than once a week), and are
      also clearly related to the course grade, even this factor will not generate
      prolonged and effective study behavior. Effective college teaching is essentially
      a form of aversive control, but if done properly the aversiveness is quite mild,
      and such aversive control can be responsible for the development of large and
      valuable intellectual repertoires.

PMID- 22478108
TI  - Teaching students to analyze examples of classical conditioning.

PMID- 22478109
TI  - A catalyst for discussion on observables, inference, and behaviorism.

PMID- 22478110
TI  - The function of journals.

PMID- 22478111
TI  - ABA presidential address: the aim, progress, and evolution of behavior analysis.

PMID- 22478112
TI  - Social behavior as discriminative stimulus and consequence in social
      anthropology.
AB  - A behavior analysis is provided for three topics in social anthropology. Food,
      social relations, and ritual behaviors can enter into contingencies both as
      functional consequences and as discriminative stimuli for the reinforcement of
      behaviors through generalized social consequences. Many "symbolic" behaviors,
      which some social anthropologists believe go beyond an individual material basis,
      are analyzed as the latter. It is shown how the development of self-regulation to
      bridge remote consequences can undermine a group's generalized social control. It
      is also shown that rituals and taboos can be utilized to maintain generalized
      social compliance, which in turn can maintain both the community's verbal
      behavior and other group behaviors that bridge indirect and remote consequences.

PMID- 22478113
TI  - An empirical update (1969-1989) of D. L. Krantz's thesis that the experimental
      analysis of behavior is isolated.
AB  - Citation data from 1970 to 1989 were examined in order to determine whether the
      "isolation" of the experimental analysis of behavior (EAB) that was originally
      documented by Krantz (1971, 1972) has persisted beyond the early 1970s. Our
      findings from analyses of the Journal of the Experimental Analysis of Behavior
      (JEAB) and of related journals support the following conclusions: (1) In the 20
      year period since 1969, JEAB has continued to cite its own articles ("self-cite")
      at a higher rate than related journals; (2) JEAB's self-citation rate decreased
      by a larger amount since 1969 than did that of related journals; and (3) JEAB was
      cited with diminishing frequency by some related journals during the 20-year
      period. These findings and other disciplinary comparisons provide information
      relevant to the issue of the health of behavior analysis and related specialties.

PMID- 22478114
TI  - Probability and radical behaviorism.
AB  - The concept of probability appears to be very important in the radical
      behaviorism of Skinner. Yet, it seems that this probability has not been
      accurately defined and is still ambiguous. I give a strict, relative frequency
      interpretation of probability and its applicability to the data from the science
      of behavior as supplied by cumulative records. Two examples of stochastic
      processes are given that may model the data from cumulative records that result
      under conditions of continuous reinforcement and extinction, respectively.

PMID- 22478116
TI  - Encouraging applied behavioral theses in nonbehavioral programs.

PMID- 22478115
TI  - Brave new world revisited revisited: Huxley's evolving view of behaviorism.
AB  - Aldous Huxley's Brave New World has served as a popular and powerful source of
      antibehavioral sentiment. Several of Huxley's works are examined in order to
      ascertain his true thoughts regarding behaviorism. Early in his career Huxley
      failed to appreciate aspects of behavioral theory (e.g., an appreciation of
      heredity) or the good ends to which it could be employed. Huxley's later works
      portrayed behaviorism in a much more positive light, and he believed that
      behavioral science, along with spiritual enlightenment, might help save humanity
      from the Brave New World he predicted.

PMID- 22478118
TI  - Where is "Animal intelligence"?

PMID- 22478119
TI  - Stimulus control shaping and stimulus control topographies.

PMID- 22478120
TI  - Memories of psychology in the twenties.

PMID- 22478121
TI  - The renaissance of the experimental analysis of human behavior.
AB  - Ten years ago, a number of authors commented on the dismal state of the basic
      research area known as the experimental analysis of human behavior (EAHB). At
      that time, data on the number of research articles using human subjects published
      in the Journal of the Experimental Analysis of Behavior (JEAB) indicated little
      progress since the early 1960s. However, updated publication data through 1991
      reveal that EAHB research has accelerated in the last decade, reaching a peak of
      nearly half of all research articles published in JEAB, with an increasing trend
      evident. The increase in this percentage is not due solely to a long-term
      declining trend in the total number of experimental articles in JEAB using either
      human or nonhuman subjects, a trend that appears to have slowed or stabilized in
      the last 6 years. These data indicate that the EAHB has made dramatic progress in
      a decade and is healthy and growing.

PMID- 22478122
TI  - Skinner and a solution to the problem of inner events.
AB  - Skinner's treatment of inner states has been criticized not only by cognitivists
      but also by people who are close to behaviorist views. In particular, critics
      have argued that because of the limited conceptual resources of his scientific
      framework, Skinner cannot account for "mental" phenomena such as the qualitative
      character of feelings, conscious contents, or states of awareness. The present
      paper claims that these criticisms are mistaken. By paying careful attention to
      Skinner's strict physicalist position and by employing a consistent physicalist
      terminology, it can be shown that Skinner is able to account for the phenomena in
      question.

PMID- 22478123
TI  - Variation and selection: The evolutionary analogy and the convergence of
      cognitive and behavioral psychology.
AB  - The empirical and theoretical work of both operant and cognitive researchers has
      increasingly appealed to evolutionary concepts. In particular, both traditional
      operant studies of extinction-induced behavior and cognitive investigations of
      creativity and problem solving converge on the fundamental evolutionary
      principles of variation and selection. These contemporary developments and their
      implications for the alleged preparadigmatic status of psychology are discussed.

PMID- 22478124
TI  - The psychological present.
AB  - The present paper compares behavior-analytic and cognitive treatments of the
      concept of psychological history with regard to its role in current action. Both
      treatments take the position that the past bears some responsibility for the
      present, and are thereby obligated to find a means of actualizing the past in the
      present. Both do so by arguing that the past is brought to bear in the present
      via the organism. Although the arguments of the two positions differ on this
      issue, neither provides a complete account. An unconventional treatment of
      psychological history is proposed, the logic of which is exemplified in
      anthropological, biological, and psychological perspectives. The unconventional
      treatment in psychological perspective holds that (a) the organism's interaction
      with its environment, not the organism itself, changes with experience; and (b)
      the past interactions of an organism exist as, and only as, the present
      interactions of that organism. This solution to the problem of psychological
      history provides obligations and opportunities for analysis that are not
      available when the more conventional positions of cognitivism and behavior
      analysis are adopted.

PMID- 22478125
TI  - Trends in the measurement of social validity.
AB  - Since its inception in the mid-1970s, social validity has provided applied
      behavior analysts with a critical measure of the social impact and importance of
      their interventions. Recent discussion, however, has questioned the use of this
      construct in regard to the frequency and types of social validty measures
      employed in research. Despite the ensuing discussion, virtually no quantitative
      information has been made available to frame various perspectives and opinions.
      The purpose of this report is to present a content analysis of social validity
      measures used over the previous 20 years. Social validity was assessed along
      three dimensions: (a) type of assessment, (b) focus of assessment, and (c) time
      of assessment. Articles published in the Journal of Applied Behavior Analysis
      (1968-1990) and Behavior Modification (1977-1990) were surveyed. The results of
      the content analysis indicate that current applications of social validation
      procedures are presented in 20% of the articles surveyed. The majority of
      articles used subjective evaluation of outcomes following intervention to assess
      social validity. In addition, the data indicated that normative comparison was a
      rarely used method of social validation and that its use has been decreasing over
      time.

PMID- 22478126
TI  - A suggestion for describing combinations of response-dependent and response
      independent events.

PMID- 22478127
TI  - Convergences with behavior analysis: Recommendations from the rhetoric of
      inquiry.
AB  - This analysis speculates on reasons why behavior analysis has not had the
      professional impact it desires, and suggests that increased contact with non
      behavior-analytic research traditions and increased research in the area of
      verbal behavior may reverse the profession's fortunes. Behaviorists have accured
      a number of advantages from constituting themselves as a separate school in
      psychology. Nonetheless, school status can lead to isolation from other research
      traditions and can restrict communicative encounters with outside scholars to
      efforts to attack their research programs and defend one's own. Efforts to
      counteract these tendencies should help bring behavior analysis into the
      mainstream of contemporary social science research. In addition, if behavior
      analysts reconsider some of their assumptions about verbal and nonverbal
      behaviors and some of their methodological assumptions about how verbal behavior
      is to be studied, and if they place verbal behavior research on center stage,
      they may make substantive contributions to the contemporary multidisciplinary
      study of language.

PMID- 22478128
TI  - Separating discriminative and function-altering effects of verbal stimuli.
AB  - Ever since Skinner's first discussion of rule-governed behavior, behavior
      analysts have continued to define rules, either explicitly or implicitly, as
      verbal discriminative stimuli. Consequently, it is not difficult to find, in the
      literature on rule-governed behavior, references to stimulus control, antecedent
      control, or to rules occasioning behavior. However, some verbal stimuli have
      effects on behavior that are not easily described as discriminative. Such stimuli
      don't evoke behavior as discriminative stimuli, but rather alter the functions of
      other stimuli in a manner analogous to operant and respondent conditioning.
      Hence, this type of control has been called function altering. Any known stimulus
      function (e.g., evocative, or [conditioned] reinforcing or punishing functions)
      can apparently be altered by such function-altering stimuli. Describing these
      stimuli as discriminative stimuli obscures their possible function-altering
      effects and consequently may retard inquiry into them. This paper encourages
      behavior analysts to begin separating the discriminative and function-altering
      effects of verbal stimuli and suggests that by doing so, behavior analysts may
      better understand what may be most unique about these stimuli. Results from
      several experiments, especially those in which children served as subjects, are
      analyzed. Finally, some speculations are offered concerning the genesis of
      function-altering stimuli.

PMID- 22478129
TI  - Behavior analysis and mechanism: One is not the other.
AB  - Behavior analysts have been called mechanists, and behavior analysis is said to
      be mechanistic; that is, they are claimed to be aligned with the philosophy of
      mechanism. What this means is analyzed by (a) examining standard and specialized
      dictionary and encyclopedia definitions and descriptions of mechanism and its
      cognates and (b) reviewing contemporary representations of the mechanistic
      worldview in the literature on the philosophy of psychology. Although the term
      mechanism and its cognates are sometimes an honorific (e.g., "natural science"),
      their standard meanings, usages, and functions in society, science, psychology,
      and philosophy do not aptly characterize the discipline. These terms
      mischaracterize how behavior analysts conceptualize (a) the behavior of their
      subjects and the individuals with whom they work and (b) their own behavior as
      scientists. Discussion is interwoven throughout about the nature of terms and
      definitions in science.

PMID- 22478130
TI  - On Morris's mechanisms.

PMID- 22478131
TI  - Behavior analysis is not ultimately about behavior.

PMID- 22478132
TI  - Behavior analysis and S. C. Pepper's other mechanism.

PMID- 22478133
TI  - Beyond the illusion of a mechanistic psychology.

PMID- 22478134
TI  - Contextualistic mechanism or mechanistic contextualism?: The straw machine as tar
      baby.

PMID- 22478135
TI  - Comments about Morris's paper.

PMID- 22478136
TI  - Participation by women in behavior analysis. II: 1992.
AB  - Participation by women and men in (a) the editorial process and publication of
      three behavior analysis journals, (b) leadership in the Association for Behavior
      Analysis (ABA) and the Society for the Experimental Analysis of Behavior, and (c)
      participation in the 1982 and 1991 conventions of the Association for Behavior
      Analysis are described. The data indicate that the relative involvement of women
      in all three areas is lower than the percentage of ABA members who are women
      (31%) and is considerably lower than the percentage of women in society at large
      (51%). This underrepresentation of women in editorial and leadership roles in
      behavior analysis mirrors the reported phenomenon of a glass ceiling for women in
      leadership roles in business and industry. The men who control our institutions
      are asked to share power and responsibility by increasing the involvement of
      women in behavior analysis.

PMID- 22478137
TI  - The professional credential in behavior analysis.
AB  - The quality of behavior analysis is of interest to many individuals within the
      community. Other professionals are including behavior analysis in their
      credentials and excluding from practice those qualified behavior analysts who do
      not have their credentials. Existing credentialing programs do not seem to
      regulate behavior analysis adequately. This article examines reasons for a
      professional credential in behavior analysis, various components of credentialing
      programs, the forms of programs available, and alternative professional
      credentials for behavior analysts.

PMID- 22478138
TI  - Applying the least restrictive alternative principle to treatment decisions: A
      legal and behavioral analysis.
AB  - The least restrictive alternative concept is widely used in mental health law.
      This paper addresses how the concept has been applied to treatment decisions. The
      paper offers both a legal and a behavioral analysis to some problems that have
      emerged in recent years concerning the selection of behavioral procedures used to
      change client behavior. The paper also offers ways of improving the application
      of the concept, which involve developing a more behaviorally functional
      perspective toward restrictiveness.

PMID- 22478139
TI  - ABA accreditation of graduate programs of study.
AB  - ABA now offers accreditation for graduate programs of study in behavior analysis.
      Minimum standards include curriculum topics in (a) the principles of behavior,
      (b) within-subject research methodology and direct observation of behavior, (c)
      conceptual issues, and (d) behavioral interventions, as well as a thesis,
      dissertation, review paper, or general examination that is based on a behavior
      analytic approach to problems or issues. Accreditation is viewed as one part of a
      process concerned with demonstrating that a person trained according to a given
      set of standards is more effective in utilizing the techniques of a science than
      a person who is not so trained.

PMID- 22478140
TI  - Mands across the water: A report on the application of the picture-exchange
      communication system in Peru.

PMID- 22478141
TI  - Concomitants, categories, and constraints.

PMID- 22478142
TI  - Windows on the 21st century.
AB  - Behavior analysis is a cultural system of which the Association for Behavior
      Analysis is a component cultural system. As cultural systems, they are composed
      of interlocking behavioral contingencies that constitute their cultural
      practices. Critical to the survival of both cultural systems is the frequency of
      interaction with and the nature of the content of the behavioral contingencies
      composing those cultural practices. The strengths of behavior analysis as a
      cultural system include its disciplinary character and its worldwide community of
      scientists and practitioners; its ability to be integrated into a scientific
      worldview; its track record in providing effective solutions to problems of
      importance to society; and the high levels of intellect, competence, and
      commitment that are characteristic of its participants. Weaknesses of behavior
      analysis are its status as an academic orphan, its relatively small size and its
      underdeveloped professional identity, and a lack of sociopolitical sophistication
      among many of its members. Behavior analysis will need to maximize its strengths
      and mitigate its weaknesses if it is to take advantage of the many opportunities
      available for growth in the modern world.

PMID- 22478143
TI  - Credentialing behavior analysts and the Florida behavior analysis certification
      program.
AB  - Nearly 1,000 professions are regulated in one or more of the 50 states. Behavior
      analysis is not regulated as a distinct profession except in Florida. Typically,
      the regulation of behavior analysis is subsumed within other professions (such as
      psychology) whose practices often differ considerably from those of behavior
      analysis. This paper provides an overview of the common methods of regulation and
      discusses the pros and cons of regulating behavior analysis independently of
      other professions. It also describes how one state agency in Florida has
      regulated behavior analysts through the Behavior Analysis Certification Program,
      with a historical summary of the development of the training curriculum and
      certification examination and description of current efforts to refine and expand
      the regulation of behavior analysts. Suggestions for establishing formal
      regulation of behavior analysts in other states are also given.

PMID- 22478144
TI  - Discriminating utopian from dystopian literature: Why is walden two considered a
      dystopia?
AB  - Skinner thought of Walden Two as a utopia, but many literary critics consider it
      a dystopia. The present paper examines works by several authors of utopian
      literature in an effort to determine what elements lead critics to classify works
      as "dystopian." Common elements seem to include (a) suspicion of scientific
      social planning, (b) the unhappiness of the characters portrayed, (c) suspicion
      of sources of control of behavior outside the individual, (d) violation of a
      presumed inherent need to struggle, and (e) suspicion of behavioral methods of
      governance. The elements Walden Two shares with other utopias and dystopias are
      examined, and the conclusion is offered that Walden Two could not be considered a
      dystopia for any of the traditional reasons. Instead, the negative view of Walden
      Two seems to be an outgrowth of literary devices and general negative reactions
      to behavioral determinism.

PMID- 22478145
TI  - Ogden R. Lindsley and the historical development of precision teaching.
AB  - This paper presents the historical developments of precision teaching, a
      technological offshoot of radical behaviorism and free-operant conditioning. The
      sequence progresses from the scientific precursors of precision teaching and the
      beginnings of precision teaching to principal developments since 1965.
      Information about the persons, events, and accomplishments presented in this
      chronology was compiled in several ways. Journals, books, and conference
      presentations provided the essential information. The most important source for
      this account was Ogden Lindsley himself, because Lindsley and his students
      established the basic practices that define precision teaching.

PMID- 22478146
TI  - Establishing operations.
AB  - The first two books on behavior analysis (Skinner, 1938; Keller & Schoenfeld,
      1950) had chapter-length coverage of motivation. The next generation of texts
      also had chapters on the topic, but by the late 1960s it was no longer being
      given much treatment in the behavior-analytic literature. The present failure to
      deal with the topic leaves a gap in our understanding of operant functional
      relations. A partial solution is to reintroduce the concept of the establishing
      operation, defined as an environmental event, operation, or stimulus condition
      that affects an organism by momentarily altering (a) the reinforcing
      effectiveness of other events and (b) the frequency of occurrence of that part of
      the organism's repertoire relevant to those events as consequences.
      Discriminative and motivative variables can be distinguished as follows: The
      former are related to the differential availability of an effective form of
      reinforcement given a particular type of behavior; the latter are related to the
      differential reinforcing effectiveness of environmental events. An important
      distinction can also be made between unconditioned establishing operations
      (UEOs), such as food deprivation and painful stimulation, and conditioned
      establishing operations (CEOs) that depend on the learning history of the
      organism. One type of CEO is a stimulus that has simply been paired with a UEO
      and as a result may take on some of the motivative properties of that UEO. The
      warning stimulus in avoidance procedures is another important type of CEO
      referred to as reflexive because it establishes its own termination as a form of
      reinforcement and evokes the behavior that has accomplished such termination.
      Another CEO is closely related to the concept of conditional conditioned
      reinforcement and is referred to as a transitive CEO, because it establishes some
      other stimulus as a form of effective reinforcement and evokes the behavior that
      has produced that other stimulus. The multiple control of human behavior is very
      common, and is often quite complex. An understanding of unlearned and learned
      establishing operations can contribute to our ability to identify and control the
      various components of such multiple determination.

PMID- 22478147
TI  - Establishing operations: Another step toward a functional taxonomy of
      environmental events.

PMID- 22478148
TI  - The application of establishing operations.

PMID- 22478149
TI  - The establishing operation revisited.

PMID- 22478150
TI  - Coming to terms with establishing operations.

PMID- 22478151
TI  - Establishing operations and the discriminative stimulus.

PMID- 22478152
TI  - Author's response.

PMID- 22478153
TI  - Mechanism and contextualism in behavioral pharmacology.

PMID- 22478154
TI  - Is contextualism productive?

PMID- 22478155
TI  - Pepper with a pinch of psalt.

PMID- 22478156
TI  - A mote in the mind's eye.

PMID- 22478157
TI  - Mechanism and contextualism in behavior analysis: Just some observations.

PMID- 22478158
TI  - The dimensions of clinical behavior analysis.
AB  - In most talk therapies for outpatient adults, the therapist has no contro over
      the client's daily life or contingencies outside the treatment session. The
      fundamental theoretical issue facing the behavior analyst is, "How can the
      talking that goes on during the session help the client with problems that occur
      outside the session in the client's daily life?" An historical analysis and the
      application of verbal behavior principles are used to answer the question and
      form the basis of clinical behavior analysis (CBA). The implications of CBA range
      from providing a theoretical base for psychotherapy to suggesting new forms of
      treatment.

PMID- 22478159
TI  - Some applied implications of a contemporary behavior-analytic account of verbal
      events.

PMID- 22478160
TI  - A behavior-analytic view of psychological health.
AB  - This paper argues that a behavioral analysis of psychological health is useful
      and appropriate. Such an analysis will allow us to better evaluate intervention
      outcomes without resorting only to the assessment of pathological behavior, thus
      providing an alternative to the Diagnostic and Statistical Manual system of
      conceptualizing behavior. The goals of such an analysis are to distinguish
      between people and outcomes using each term of the three-term contingency as a
      dimension to consider. A brief review of other efforts to define psychological
      health is provided. Laboratory approaches to a behavioral analysis of healthy
      behavior are presented along with shortcomings in our science that impede our
      analysis. Finally, we present some of the functional characteristics of
      psychological health that we value.

PMID- 22478162
TI  - A teleconference with professor Fred S. Keller.

PMID- 22478161
TI  - Persuasion criteria in research and practice: Gathering more meaningful
      psychotherapy data.
AB  - Psychotherapy research should ultimately benefit the psychotherapy client.
      Unfortunately, traditional psychotherapy research continues to have little
      influence on practicing clinicians and, therefore, does not benefit psychotherapy
      clients. As behavior analysts begin to show interest in this area of research,
      they may be in a position to improve its quality. We argue that traditional
      psychotherapy researchers have become prematurely wedded to a methodology that
      does not address the concerns of clinical audiences. Furthermore, we make a case
      for defining and evaluating psychotherapy data in terms of its capacity to
      influence both researchers and clinicians. We also suggest several alternative
      methods for gathering psychotherapy data based on the case formulation approach.
      We argue that this approach may be one of the most promising methods for
      gathering useful psychotherapy data.

PMID- 22478163
TI  - Do establishing operations alter reinforcement effectiveness?
AB  - Michael (this issue) defines an establishing operation (EO), such as food
      deprivation, as (a) altering the effectiveness of reinforcement as well as (b)
      evoking behavior. Although this dual role for EOs is compelling, it is possible
      that such operations have only evocative effects (i.e., function only in the form
      of antecedent control). The main question raised here is how the reinforcement
      altering function can be experimentally analyzed. Evolutionary and conceptual
      implications of the two-function EO are also considered.

PMID- 22478164
TI  - The case against physicalism in the analysis of behavior.

PMID- 22478165
TI  - Response to Myers on participation of women in behavior analysis: Right problem,
      wrong source.

PMID- 22478166
TI  - More participation by women in behavior analysis: Reply to Neef.

PMID- 22478167
TI  - Editorial.

PMID- 22478168
TI  - Memorial minute for B. F. Skinner.

PMID- 22478170
TI  - Ordinary language: The contributions of Gilbert Ryle and John Austin to the
      experimental analysis of behavior.
AB  - The aim of this paper is to show how "conceptual analysis"-the philosophical
      method used by Gilbert Ryle and John Austin-can contribute to behavior analysis
      in general and in particular to the elucidation and development of views put
      forward by B. F. Skinner. One of the key requirements is a sensitivity to the
      precise circumstances in which particular combinations of words are uttered.
      Without such sensitivity, it is difficult to make informed decisions as to when
      ways of talking should be changed and when they should be left as they are.

PMID- 22478169
TI  - Activity anorexia: An interplay between basic and applied behavior analysis.
AB  - The relationship between basic research with nonhumans and applied behavior
      analysis is illustrated by our work on activity anorexia. When rats are fed one
      meal a day and allowed to run on an activity wheel, they run excessively, stop
      eating, and die of starvation. Convergent evidence, from several different
      research areas, indicates that the behavior of these animals and humans who self
      starve is functionally similar. A biobehavioral theory of activity anorexia is
      presented that details the cultural contingencies, behavioral processes, and
      physiology of anorexia. Diagnostic criteria and a three-stage treatment program
      for activity-based anorexia are outlined. The animal model permits basic research
      on anorexia that for practical and ethical reasons cannot be conducted with
      humans. Thus, basic research can have applied importance.

PMID- 22478171
TI  - Taking hermeneutics to science: Prospects and tactics suggested by the work of B.
      F. Skinner.
AB  - Skinner's contributions to the understanding of behavior are typically viewed as
      being in sufficiently tight alignment with traditional science to prevent their
      amenability to alternative discourses such as hermeneutics. However, it is
      possible to identify several concepts at work in radical behaviorism that might
      constitute its common ground with hermeneutics. The coextensiveness of individual
      and environment, the emphasis on contingency, and the interminableness of
      conversation promised by technology are among the concepts considered here,
      together with issues that are potentially problematic for the effort to find a
      common ground.

PMID- 22478172
TI  - A descriptive taxonomy of environmental operations and its implications for
      behavior analysis.
AB  - Environmental operations may be classified according to whether they have
      evocative or function-altering effects. Evocative events, such as the
      presentation of unconditioned and conditioned stimuli, establishing operations,
      and discriminative stimuli, serve to increase, decrease, or maintain the
      momentary frequency of behavior. Function-altering operations, such as operant
      and respondent conditioning, the correlation of stimuli, and the presentation of
      certain verbal stimuli, serve to increase, decrease, or maintain the evocative
      and function-altering (e.g., reinforcing or punishing) functions of other events.
      This paper expands upon the functional taxonomy of environmental events described
      by Michael (1993a). The resulting classification scheme should permit behavior
      analysts to more easily respond to similarities and differences between
      functional environmental events. This paper discusses implications of the
      suggested taxonomy for how behavior analysts talk about motivational variables,
      discriminative stimuli, the operant unit of analysis, and the distinction between
      operant and respondent conditioning.

PMID- 22478173
TI  - Bridging the schism between behavioral and cognitive analyses.
AB  - A major schism in modern scientific psychology has occurred between behavior
      analysts and cognitive psychologists. The two groups speak in different
      languages, but the languages can be translated so that they are mutually
      understandable; when either language is translated into the other, similarities
      emerge from seeming differences. We draw an analogy between the basic units of
      behavior analysis (the operant and the establishing operation) and cognitive
      psychology (the production). We argue that both units describe behavior as a
      function of motivative and discriminative antecedents. In addition, the two
      perspectives account in analogous ways for ongoing changes in motivation and for
      control by verbal statements. Adherents of the two perspectives have
      experimentally analyzed some of the same problems and fashioned similar solutions
      for applied problems. We conclude that many of the commonly cited differences
      between the two perspectives are the result of misunderstanding, and that the
      real differences need not preclude communication and collaboration. The schism
      can be bridged.

PMID- 22478174
TI  - Teleology and teleonomy in behavior analysis.
AB  - Teleological descriptions and explanations refer to purpose as consequent to a
      phenomenon. They become nonteleological if purpose is represented as antecedent
      to the phenomenon. Such nonteleological statements are called teleonomic,
      especially when they refer to antecedent genetic "programs." In behavior
      analysis, purpose is attributed to the organism's history of consequences. Such a
      history may leave a trace-physiological (mechanism) or mental (cognitivism)-or
      the issue of traces may be irrelevant (contextualism). The history or trace is
      antecedent to current responding, and thus is not a teleological concept in the
      classical sense. It could be called a teleonomic concept, but this designation is
      undesirable if it implies exclusively genetic programming, because the history or
      trace is genetically programmed in evolutionary selection but not in ontogenetic
      selection. Therefore, the concepts of teleology and teleonomy are not useful for
      behavior analysis, and invoking them can be misleading. The concept of purpose
      can be useful if it is not reified.

PMID- 22478175
TI  - Psychological behaviorism and behaviorizing psychology.
AB  - Paradigmatic or psychological behaviorism (PB), in a four-decade history of
      development, has been shaped by its goal, the establishment of a behaviorism that
      can also serve as the approach in psychology (Watson's original goal). In the
      process, PB has become a new generation of behaviorism with abundant heuristic
      avenues for development in theory, philosophy, methodology, and research.
      Psychology has resources, purview and problem areas, and nascent developments of
      many kinds, gathered in chaotic diversity, needing unification (and other things)
      that cognitivism cannot provide. Behaviorism can, within PB's multilevel
      framework for connecting and advancing both psychology and behaviorism.

PMID- 22478176
TI  - W. Edwards Deming, quality analysis, and total behavior management.
AB  - During the past 10 years, the inclusion of the word "quality" in descriptions of
      production methods, management approaches, educational systems, service system
      changes, and so forth, has grown exponentially. It appears that no new approach
      to any problem is likely to be given much consideration today without overt
      acknowledgment that some improvement in quality must be the outcome. The origins
      of the importance of quality are primarily rooted in the awakening recognition of
      the influence of W. Edwards Deming in the post-World War II restoration of
      Japanese industry. We provide a brief overview of Deming's approach to
      modernizing management methods and discuss recent criticisms from the field of
      organizational behavior management that his approach lacks emphasis on the role
      of reinforcement. We offer a different analysis of Deming's approach and relate
      its evolution to the contingencies of reinforcement for the behavior of
      consulting. We also provide an example of problem solving with Deming's approach
      in a social service setting familiar to many behavior analysts.

PMID- 22478177
TI  - Attitudes, beliefs, and behavior: Saying you like, saying you believe, and doing.

PMID- 22478178
TI  - Do as I say, not as I do.
AB  - The degree of agreement between responses to attitude questionnaires and
      responses in situations in which the content of the questionnaires is relevant is
      examined for the study of attitudes in general and for the study of environmental
      attitudes in particular. The observed low positive correlations of attitude and
      behaviour suggest that the notion that it is first necessary to change attitudes
      before one can change behaviour must be reevaluated. A review of the recent say
      do correspondence literature is followed by a comparison of attitude-behaviour
      studies with say-do correspondence studies. A more empirical approach is urged
      for the future of environmental research which offers a unique arena for the
      study of attitude-behaviour congruence.

PMID- 22478179
TI  - Addenda.

PMID- 22478180
TI  - Attitude-behavior congruity, mindfulness, and self-focused attention: A behavior
      analytic reconstruction.
AB  - Social psychologists have responded to research reporting low agreement between
      attitude measures and related behavior with attempts to explain the incongruities
      and enhance agreement. This article examines attitude-behavior incongruity from a
      behavior-analytic point of view. Traditional and behavior-analytic views of
      attitudes and behaviors are compared. In the behavior-analytic view, answering an
      attitude scale should be considered as behavior displayed by a person under
      rather unusual social conditions, not as a reflection of an enduring personal
      disposition. Reasons why questionnaire-answering behavior will not resemble
      behavior in other functionally different social conditions are reviewed. Special
      attention is extended to two representative lines of attitude-behavior research:
      mindfulness and self-focused attention. Discriminative stimuli in both areas of
      study have produced more predictable agreement between questionnaire-answering
      behavior and behavior in other settings.

PMID- 22478181
TI  - Attitudes and beliefs as verbal behavior.
AB  - Attitudes and beliefs are analyzed as verbal behavior. It is argued that shaping
      by a verbal community is an essential part of the formation and maintenance of
      both attitudes and beliefs, and it is suggested that verbal communities mediate
      the important shift in control from events in the environment (attitudes and
      beliefs as tacts) to control by other words (attitudes and beliefs as
      intraverbals). It appears that both attitudes and beliefs are constantly being
      socially negotiated through autoclitic functions. That is, verbal communities
      reinforce (a) reporting general rather than specific attitudes and beliefs, (b)
      presentation of intraverbals as if they were tacts, and (c) presentation of
      beliefs as if they were attitudes. Consistency among and between attitudes,
      beliefs, and behavior is also contingent upon the reinforcing practices of verbal
      communities. Thus, attitudes and beliefs can be studied as social behavior rather
      than as private, cognitive processes.

PMID- 22478182
TI  - Mechanistic ontology and contextualistic epistemology: A contradiction within
      behavior analysis.

PMID- 22478184
TI  - Reply to Dougherty: On measuring content diversity in the experimental analysis
      of human behavior.

PMID- 22478183
TI  - The selective renaissance of the experimental analysis of human behavior.
AB  - Two recent articles (Dougherty, Nedelmann, & Alfred, 1993; Hyten & Reilly, 1992)
      have favorably appraised the growth and health of the experimental analysis of
      human behavior as a whole. Within the last decade alone, there has been a more
      than threefold increase in the percentage of human operant papers appearing in
      the Journal of the Experimental Analysis of Behavior. In the present paper, a
      more molecular analysis is used, and some concerns are raised about the overall
      health of the field. The analysis included a determination of the rate at which
      new authors have appeared, how several areas of research have grown, and a
      contrast between the proportion of papers appearing in each of several areas of
      research during the last two decades. Two primary concerns are raised in this
      paper: (a) The recent growth within the field has been in only three select
      research areas (general schedule control, reinforcement, and stimulus control),
      and (b) there is an increasing disparity between the number of papers published
      in the few areas of research receiving the most attention and the number of
      papers published in the other areas of research receiving the least attention.
      Although the experimental analysis of human behavior has made considerable
      progress in the mere number of publications, these publications have been
      somewhat limited in scope.

PMID- 22478185
TI  - Richard J. Herrnstein: A memoir.

PMID- 22478187
TI  - Common versus distinctive species: On the logic of behavioral comparison.

PMID- 22478186
TI  - The representative animal.
AB  - The anthropocentric approach to the study of animal behavior uses representative
      nonhuman animals to understand human behavior. This approach raises problems
      concerning the comparison of the behavior of two different species. The datum of
      behavior analysis is the behavior of humans and representative animal phenotypes.
      The behavioral phenotype is the product of the ontogeny and phylogeny of each
      species, and this requires that contributions of genotype as well as behavioral
      history to experimental performance be considered. Behavior analysis tends to
      favor the ontogenetic over the phylogenetic component, yet both components are
      responsible for the performance of each individual animal. This paper raises
      questions about the role of genotype variables in the use of representative
      animals to understand human behavior. Examples indicating the role of genotype in
      human behavior are also discussed. The final section of the paper deals with
      considerations of genotype in the design of animal experiments.

PMID- 22478188
TI  - On science, scientists, and scientific vocabulary: Commentary on Harrison's "The
      representative animal".

PMID- 22478189
TI  - Reply to Harrison: The representative method.

PMID- 22478190
TI  - Discussion of comments on "The representative animal".

PMID- 22478191
TI  - Functions of the environment in behavioral evolution.
AB  - This paper explores some of the ways in which the environment functions with
      respect to behavior within an explanatory framework analogous to that of
      evolutionary biology. In both the behavioral and organic domains, the environment
      functions differently with respect to individual occurrences and evolutionary
      units. Within the behavioral domain, the problem of accounting for an occurrence
      of an operant instance differs from that of accounting for the existence of the
      operant unit of which the instance is a part. Maintaining these distinctions in
      levels of analysis within the behavioral domain, we focus first on operant units
      and operant instances as products of evolutionary processes occurring in the
      behavioral domain and second upon the causal role of the environment with respect
      to the existence of operant units and the occurrence of operant instances. The
      environment's function is selective with respect to origin, maintenance,
      suppression, and extinction of behavioral populations. At the level of operant
      instances, the environment has instantiating functions-evocative or alterative.
      Evocative functions are exemplified by discriminative relations, and alterative
      functions include both conditional and motivative relations. Implications are
      considered regarding extension of the analogy to more complex behavior
      environment relations.

PMID- 22478192
TI  - Conditioned reinforcement: Experimental and theoretical issues.
AB  - The concept of conditioned reinforcement has received decreased attention in
      learning textbooks over the past decade, in part because of criticisms of its
      validity by major behavior theorists and in part because its explanatory function
      in a variety of different conditioning procedures has become uncertain. Critical
      data from the major procedures that have been used to investigate the concept
      (second-order schedules, chain schedules, concurrent chains, observing responses,
      delay-of-reinforcement procedures) are reviewed, along with the major issues of
      interpretation. Although the role played by conditioned reinforcement in some
      procedures remains unresolved, the results taken together leave little doubt that
      the underlying idea of conditioned value is a critical component of behavior
      theory that is necessary to explain many different types of data. Other processes
      (marking, bridging) may also operate to produce effects similar to those of
      conditioned reinforcement, but these clearly cannot explain the full domain of
      experimental effects ascribed to conditioned reinforcement and should be regarded
      as complements to the concept rather than theoretical competitors. Examples of
      practical and theoretical applications of the concept of conditioned
      reinforcement are also considered.

PMID- 22478193
TI  - Acceptance and commitment therapy: Altering the verbal support for experiential
      avoidance.
AB  - Acceptance and Commitment Therapy (ACT) is a behavior-analytically-based
      psychotherapy approach that attempts to undermine emotional avoidance and
      increase the capacity for behavior change. An overview of this approach is given,
      followed by several specific examples of the techniques used within ACT. In each
      instance the behavioral rationale of these techniques is described. A
      contemporary view of verbal relations provides the basis for new approaches to
      adult outpatient psychotherapy.

PMID- 22478194
TI  - Improving cognitive therapy for depression with functional analytic
      psychotherapy: Theory and case study.
AB  - A behavioral reconceptualization of cognitive therapy is presented to illustrate
      that clinical behavior analysis (CBA) has much to offer traditional cognitive
      behavior therapy. Particular attention is given to the distinction between
      cognitive structures and products and the theoretical dilemma facing cognitive
      therapists when they attempt to devise interventions aimed at changing
      nonbehavioral entities. The distinction between rule-governed and contingency
      shaped behavior and the implications of functional analytic psychotherapy
      (Kohlenberg & Tsai, 1991) are used to resolve the dilemma and to suggest methods
      for enhancing cognitive therapy. In a case study, a CBA-enhanced version of
      cognitive therapy was introduced after 7 weeks of standard cognitive treatment
      for a 35-year-old depressed male. The client-therapist relationship provided
      opportunities during the therapy session for learning new behavior called for in
      the behaviorally reconceptualized cognitive therapy. The enhanced treatment
      improved clinical efficacy and increased the client's focus on his deficits in
      interpersonal repertoires. Because the present case study involved only one of
      several enhancements suggested by CBA, the possibility of increased efficacy from
      a more comprehensive application is discussed.

PMID- 22478195
TI  - A behavior-analytic account of depression and a case report using acceptance
      based procedures.
AB  - Although roughly 6% of the general population is affected by depression at some
      time during their lifetime, the disorder has been relatively neglected by
      behavior analysts. The preponderance of research on the etiology and treatment of
      depression has been conducted by cognitive behavior theorists and biological
      psychiatrists and psychopharmacologists interested in the biological substrates
      of depression. These approaches have certainly been useful, but their reliance on
      cognitive and biological processes and their lack of attention to environment
      behavior relations render them unsatisfactory from a behavior-analytic
      perspective. The purpose of this paper is to provide a behavior-analytic account
      of depression and to derive from this account several possible treatment
      interventions. In addition, case material is presented to illustrate an
      acceptance-based approach with a depressed client.

PMID- 22478196
TI  - Increasing the prevalence of successful children: The case for community
      intervention research.
AB  - This paper makes a case for research on community interventions on child rearing.
      Sufficient evidence has accumulated about the development of children's problem
      behavior to justify evaluating efforts to reduce the prevalence of these problems
      in whole communities. The contextual risk factors for diverse child behavior
      problems are well understood, and interventions to ameliorate individual risk
      factors have been developed and evaluated. Because interventions with individual
      children have proven to be efficacious, it is now appropriate to direct energy
      toward reducing the prevalence of children with behavior problems. At the same
      time, existing interventions have limitations. Community interventions may be
      needed to modify the larger social context for families. This paper enumerates
      possible components of a community intervention to improve child-rearing
      outcomes. Existing evidence indicates that communities would benefit from making
      parent training and family support programs available to parents. Validated
      methods of identifying and remediating academic and behavioral problems in
      schools are available, but influencing schools to adopt them remains a problem.
      Community organizing could mobilize communities to allocate the resources
      necessary to support such parenting and schooling programs as well as encourage
      their adoption. Media campaigns could foster community support and directly
      influence parenting practices. Efforts to modify peer influences to use illicit
      substances have received empirical support; similar efforts may be relevant to
      preventing other problems. The development of a science of community
      interventions on child rearing is hampered by overreliance on randomized control
      trials. For this reason, two examples of time-series experimental evaluations of
      community intervention components are described here.

PMID- 22478198
TI  - Award for lifetime achievement in behavior analysis presented to F. S. Keller,
      May 29, 1994.

PMID- 22478199
TI  - Meanings of my career.

PMID- 22478200
TI  - Physicalism, reductionism, and verbal behavior: A reply to Leigland.

PMID- 22478197
TI  - A contextual approach to research on AIDS prevention.
AB  - The acquired immune deficiency syndrome (AIDS) is a disease that is transmitted
      almost entirely through behavioral factors. In the absence of a cure or vaccine,
      the modification of AIDS-risk behavior presents a unique challenge to behavioral
      scientists and should be taken as a clear imperative by behavior analysts. This
      paper discusses the currently dominant social-cognitive theories (the health
      belief model, the theory of reasoned action, and self-efficacy theory) that have
      been widely used to predict and understand AIDS-risk behavior. Although these
      theories have generated a voluminous literature on the cognitive, attitudinal,
      and demographic correlates of AIDS-risk behavior, they have not resulted in
      specific intervention strategies to influence risky behavior, most likely because
      they fail to specify manipulable variables. As an alternative to social-cognitive
      theories, this paper evaluates the usefulness of a behavior-analytic approach to
      stem the spread of HIV infection. It examines some of the philosophical
      differences underlying cognitive and behavioral approaches that are embedded in
      mechanistic versus functional contextualistic principles. It explores the
      theoretical and practical implications of adopting either predicting and
      explaining behavior or predicting and influencing behavior as the goals of
      science. To illustrate the value of adopting the goal of prediction and
      influence, behavior-analytic research on the social context of risky sexual
      behavior in adolescents is described. The paper argues that in order to alter the
      future course of the AIDS epidemic, the behavioral sciences must move beyond
      describing cognitive and attitudinal correlates of risky behavior and focus on
      the social context of the behavior of individuals. In addition, population-wide
      changes in AIDS-risk behavior can be accomplished only if research focuses on how
      to influence larger social systems, including the media, school systems, and
      community organizations.

PMID- 22478201
TI  - Rules, culture, and fitness.
AB  - Behavior analysis risks intellectual isolation unless it integrates its
      explanations with evolutionary theory. Rule-governed behavior is an example of a
      topic that requires an evolutionary perspective for a full understanding. A rule
      may be defined as a verbal discriminative stimulus produced by the behavior of a
      speaker under the stimulus control of a long-term contingency between the
      behavior and fitness. As a discriminative stimulus, the rule strengthens listener
      behavior that is reinforced in the short run by socially mediated contingencies,
      but which also enters into the long-term contingency that enhances the listener's
      fitness. The long-term contingency constitutes the global context for the
      speaker's giving the rule. When a rule is said to be "internalized," the
      listener's behavior has switched from short- to long-term control. The fitness
      enhancing consequences of long-term contingencies are health, resources,
      relationships, or reproduction. This view ties rules both to evolutionary theory
      and to culture. Stating a rule is a cultural practice. The practice strengthens,
      with short-term reinforcement, behavior that usually enhances fitness in the long
      run. The practice evolves because of its effect on fitness. The standard
      definition of a rule as a verbal statement that points to a contingency fails to
      distinguish between a rule and a bargain ("If you'll do X, then I'll do Y"),
      which signifies only a single short-term contingency that provides mutual
      reinforcement for speaker and listener. In contrast, the giving and following of
      a rule ("Dress warmly; it's cold outside") can be understood only by reference
      also to a contingency providing long-term enhancement of the listener's fitness
      or the fitness of the listener's genes. Such a perspective may change the way
      both behavior analysts and evolutionary biologists think about rule-governed
      behavior.

PMID- 22478202
TI  - The X club and the secret ring: lessons on how behavior analysis can take over
      psychology.
AB  - In 1864 Thomas Huxley and eight fellow scientists formed a secret organization
      called the X Club, dedicated to the promotion of Darwinian theory and
      naturalistic science. Its members active for almost 40 years, the X Club acted as
      the "power behind the throne" with respect to the governance of the Royal Society
      and other British scientific groups. In 1914 Sigmund Freud formed the Secret Ring
      with six other psychoanalysts, dedicated to the covert promotion of their field
      and to the removal of impediments (persons and policies) to the acceptance of
      psychoanalysis. After over 20 years of existence, the Secret Ring disbanded,
      having succeeded in its mission. It is suggested that behavior analysis should
      adopt a similar arrangement, whereby a group of distinguished scholars quietly
      but systematically promotes the persons and practices of our field within
      psychology, with respect to awards, elected and appointed office, and governance.

PMID- 22478203
TI  - Radical behaviorism and the subjective-objective distinction.
AB  - The distinction between subjective and objective domains is central to
      traditional psychology, including the various forms of mediational stimulus
      organism-response neobehaviorism that treat the elements of a subjective domain
      as hypothetical constructs. Radical behaviorism has its own unique perspective on
      the subjective-objective distinction. For radical behaviorism, dichotomies
      between subjective and objective, knower and known, or observer and agent imply
      at most unique access to a part of the world, rather than dichotomous ontologies.
      This perspective leads to unique treatments of such important philosophical
      matters as (a) dispositions and (b) the difference between first- and third
      person psychological sentences.

PMID- 22478204
TI  - Stimulus control: part I.
AB  - In his effort to distinguish operant from respondent conditioning, Skinner
      stressed the lack of an eliciting stimulus and rejected the prevailing stereotype
      of Pavlovian "stimulus-response" psychology. But control by antecedent stimuli,
      whether classified as conditional or discriminative, is ubiquitous in the natural
      setting. With both respondent and operant behavior, symmetrical gradients of
      generalization along unrelated dimensions may be obtained following differential
      reinforcement in the presence and the absence of the stimulus. The slopes of
      these gradients serve as measures of stimulus control, and they can be steepened
      without applying differential reinforcement to any two points along the test
      dimension. Increases and decreases in stimulus control occur under the same
      conditions as those leading to increases and decreases in observing responses,
      indicating that it is the increasing frequency and duration of observation (and
      perhaps also of attention) that produces the separation in performances during
      discrimination learning.

PMID- 22478205
TI  - Introduction: how the happy few might become the competent many.

PMID- 22478207
TI  - Essential content for training behavior analysis practitioners.
AB  - A recent national survey of 265 behavior analysts has produced a list of 12
      content areas and 108 tasks that the group felt were essential in the training of
      behavior analyst practitioners. The survey methodology, sample demographics, and
      survey results are summarized. The implications of these results are discussed as
      they relate to instruction in behavior analysis and the standards of practice of
      behavior analyst practitioners. The final task list of essential content is
      provided.

PMID- 22478206
TI  - Teaching performance management using behavior analysis.
AB  - A special undergraduate track in performance management, taught using behavior
      analysis principles, is described. The key elements of the program are presented,
      including the point systems and other reinforcement contingencies in the classes,
      the goals of the instructional activities, and many of the requirements used to
      evaluate student performance. Finally, the article provides examples of the
      performance management projects students have conducted with local businesses.

PMID- 22478208
TI  - Contingency diagrams as teaching tools.
AB  - Contingency diagrams are particularly effective teaching tools, because they
      provide a means for students to view the complexities of contingency networks
      present in natural and laboratory settings while displaying the elementary
      processes that constitute those networks. This paper sketches recent developments
      in this visualization technology and illustrates approaches for using contingency
      diagrams in teaching.

PMID- 22478209
TI  - A model of cause-effect relations in the study of behavior.
AB  - A three-phase model useful in teaching the analysis of behavior is presented. The
      model employs a "black box" behavior inventory diagram (BID), with a single
      output arrow representing behavior and three input arrows representing stimulus
      field, reversible states, and conditioning history. The first BID describes the
      organism at Time 1, and the second describes it at Time 2. Separating the two
      inventory diagrams is a column for the description of the intervening procedure.
      The model is used as a one-page handout, and students fill in the corresponding
      empty areas on the sheet as they solve five types of application problems.
      Instructors can use the BID to shape successive approximations in the accurate
      use of behavior-analytic vocabulary, conceptual analysis, and applications of
      behavior-change strategies.

PMID- 22478210
TI  - A descriptive notation system for contingency diagramming in behavior analysis.
AB  - We describe a notation system for diagramming behavioral contingencies. The
      system is descriptive. Stimulus functions are not represented with special
      symbols, such as S(R), S(D), or UCS, but are simply described in terms of the
      relation between behavior and stimulus change, and the resulting outcome. The
      system is atheoretical, self-explanatory, and easy to use. Our goal is to provide
      an approach to contingency diagramming for the student that represents directly
      the exact relations and outcomes involved in operant and respondent processes.

PMID- 22478211
TI  - State notation for teaching about behavioral procedures.
AB  - Complex operant procedures are not easy to describe unambiguously and several
      abstract notation systems have been developed for such description. Although they
      have not been generally adopted, such systems could be especially valuable to the
      teacher and student of behavior analysis, functioning like other figures and
      graphs as visual aids to ordinary verbal description. One of these systems, state
      notation, is described in some detail, and examples are provided of its use in
      teaching about behavior analysis.

PMID- 22478212
TI  - A classroom demonstration of self-monitoring, reactivity, and interobserver
      agreement.
AB  - A brief classroom demonstration designed to introduce students to the concepts of
      self-monitoring, reactivity, and interobserver agreement is presented. The
      demonstration provides students with opportunities to monitor their own behavior,
      record the behavior of others, and calculate interobserver agreement percentages.
      Results of using the demonstration with students from two classes are presented.

PMID- 22478213
TI  - Rat lab for fun and profit.
AB  - Many applied behavior analysts have little or no personal exposure to the basic
      animal experimentation that provided the foundation for applied behavior
      analysis. However, personal experience in the animal laboratory provides many
      benefits to students of applied behavior analysis. Animal laboratory experience
      provides convincing, vivid illustrations of basic principles of learning and
      facilitates generalization and application of the basic principles. The
      laboratory experience also teaches interpersonal skills that may be important in
      future employment in applied fields. The animal laboratory can also provide
      public relations opportunities, especially with university-sponsored events such
      as the Rat Olympics. These points, as well as concerns about the resources needed
      for an animal laboratory and compliance with federal animal-use guidelines, are
      addressed. It is concluded that the animal laboratory offers many educational
      profits to students while making learning fun for a reasonable outlay of effort
      and resources.

PMID- 22478214
TI  - Looking for a way to improve your behavior analysis lectures? Try guided notes.

PMID- 22478215
TI  - I'd been doing it wrong for so long it looked like right to me: using case method
      to teach introduction to applied behavior analysis.

PMID- 22478216
TI  - Analysis of complex human behavior: a reply to Staats.

PMID- 22478217
TI  - Some old work for the behavior-analytic community: introduction.

PMID- 22478218
TI  - "Reinforcement" in behavior theory.
AB  - In its Pavlovian context, "reinforcement" was actually a descriptive term for the
      functional relation between an unconditional and a conditional stimulus. When it
      was adopted into operant conditioning, "reinforcement" became the central concept
      and the key operation, but with new qualifications, new referents, and new
      expectations. Some behavior theorists believed that "reinforcers" comprise a
      special and limited class of stimuli or events, and they speculated about what
      the essential "nature of reinforcement" might be. It is now known that any
      stimulus can serve a reinforcing function, with due recognition of such
      parameters as subject species characteristics, stimulus intensity, sensory
      modality, and schedule of application. This paper comments on these developments
      from the stand-point of reflex behavior theory.

PMID- 22478219
TI  - Contingency and behavior analysis.
AB  - The concept of contingency is central to theoretical discussions of learned
      behavior and in the application of learning research to problems of social
      significance. This paper reviews three aspects of the contingency concept as it
      has been developed by behavior analysts. The first is the empirical analysis of
      contingency through experimental studies of both human and nonhuman behavior. The
      second is the synthesis of experimental studies in theoretical and conceptual
      frameworks to yield a more general account of contingency and to integrate the
      concept with other behavioral processes. The third aspect is one of practical
      considerations in the application of the contingency concept in both laboratory
      and applied settings.

PMID- 22478220
TI  - Jacques Loeb, B. F. Skinner, and the legacy of prediction and control.
AB  - The biologist Jacques Loeb is an important figure in the history of behavior
      analysis. Between 1890 and 1915, Loeb championed an approach to experimental
      biology that would later exert substantial influence on the work of B. F. Skinner
      and behavior analysis. This paper examines some of these sources of influence,
      with a particular emphasis on Loeb's firm commitment to prediction and control as
      fundamental goals of an experimental life science, and how these goals were
      extended and broadened by Skinner. Both Loeb and Skinner adopted a pragmatic
      approach to science that put practical control of their subject matter above
      formal theory testing, both based their research programs on analyses of
      reproducible units involving the intact organism, and both strongly endorsed
      technological applications of basic laboratory science. For Loeb, but especially
      for Skinner, control came to mean something more than mere experimental or
      technological control for its own sake; it became synonomous with scientific
      understanding. This view follows from (a) the successful working model of science
      Loeb and Skinner inherited from Ernst Mach, in which science is viewed as human
      social activity, and effective practical action is taken as the basis of
      scientific knowledge, and (b) Skinner's analysis of scientific activity, situated
      in the world of direct experience and related to practices arranged by scientific
      verbal communities. From this perspective, prediction and control are human acts
      that arise from and are maintained by social circumstances in which such acts
      meet with effective consequences.

PMID- 22478221
TI  - Units of interaction, evolution, and replication: organic and behavioral
      parallels.
AB  - Organic and behavioral evolution both involve variation, selection, and
      replication with retention; but the individuals involved in these processes
      differ in the two kinds of evolution. In this paper, biological units of
      evolution, selection, and retention are compared with analogous units at the
      behavioral level. In organic evolution, natural selection operates on variations
      among organisms within a species, with the result of preserving in future
      generations of organisms those heritable characteristics that contributed to the
      organism's survival and reproduction. Species evolve as characteristics of the
      population change as a result of past selection. Continuity in a lineage in the
      biosphere is maintained by replication of genes with retention of organismic
      characteristics across successive generations of organisms. In behavioral
      evolution, reinforcement operates on variations among responses within an
      operant, with the result of preserving in future responses those characteristics
      that resulted in reinforcement. Continuity in a behavioral lineage, within the
      repertoire of a given organism, appears to involve retention and replication, but
      the unit of retention and replication is unknown. We suggest that the locus of
      retention and replication is the nervous system of the behaving organism.

PMID- 22478222
TI  - Stimulus control: part II.
AB  - The second part of my tutorial stresses the systematic importance of two
      parameters of discrimination training: (a) the magnitude of the physical
      difference between the positive and the negative stimulus (disparity) and (b) the
      magnitude of the difference between the positive stimulus, in particular, and the
      background stimulation (salience). It then examines the role these variables play
      in such complex phenomena as blocking and overshadowing, progressive
      discrimination training, and the transfer of control by fading. It concludes by
      considering concept formation and imitation, which are important forms of
      application, and recent work on equivalence relations.

PMID- 22478224
TI  - What every student of behavior analysis ought to learn: a system for classifying
      the multiple effects of behavioral variables.
AB  - An accurate repertoire of tacts and intraverbals about behavior is essential for
      scientific and technical communication. All behavioral effects of the environment
      can be classified in an eight-cell arrangement created by three dichotomies:
      respondent versus operant, evocative versus function altering, and unlearned
      versus learned. By refining some old definitions and inventing a few new terms
      and symbols, it becomes possible to locate any functional relation in the eight
      cells of this set of categories. Much instruction about behavior analysis can
      then focus on helping students master a two-part repertoire consisting of (a)
      providing the term (or symbol) when given a description of a relevant situation
      and (b) describing the environmental and behavioral evidence for the relation
      when given the term (or symbol). This system of analysis is described and
      illustrated with sample questions and answers that teach about the system.

PMID- 22478225
TI  - Behavior-analytic repertoires: where will they come from and how can they be
      maintained?
AB  - The field of behavior analysis faces a number of issues concerning its existence
      as a discipline and as a profession, including (a) identification of the
      knowledge and skills comprising the repertoire of competent behavior analysts,
      (b) the nature of the curricula that will produce the scientists and
      practitioners needed by the discipline, (c) identification of the generic
      professional and social skills required for any successful professional career,
      (d) academic employment opportunities for behavior analysts, and (e) the
      maintenance of behavior-analytic repertoires. Recommendations are offered as
      possible solutions to problems raised with respect to each of these issues.

PMID- 22478226
TI  - Fostering multiple repertoires in undergraduate behavior analysis students.
AB  - Eight techniques used by the author in teaching an introductory applied behavior
      analysis course are described: (a) a detailed study guide, (b) frequent tests,
      (c) composition of practice test questions, (d) in-class study groups, (e)
      fluency building with a computerized flash-card program, (f) bonus marks for
      participation during question-and-answer sessions, (g) student presentations that
      summarize and analyze recently published research, and (h) in-class behavior
      analysis of comic strips. Together, these techniques require an extensive amount
      of work by students. Nevertheless, students overwhelmingly prefer this approach
      to the traditional lecture-midterm-final format, and most earn an A as their
      final course grade.

PMID- 22478227
TI  - Three nice labs, no real rats: a review of three operant laboratory simulations.
AB  - The operant laboratory, once the foundation for a curriculum in behavior
      analysis, has become almost impossible to maintain because of costs, federal
      regulations, and other factors. Fortunately, over the years several computer
      simulations of animal labs have been developed. This paper describes, compares,
      and contrasts three simulations and concludes that in general, they are effective
      and offer an alternative to the real thing.

PMID- 22478228
TI  - Using computers to teach behavior analysis.
AB  - When it is impractical to provide behavior analysis students with extensive
      laboratory experience using real organisms, computers can provide effective
      demonstrations, simulations, and experiments. Furthermore, such computer programs
      can establish contingency-shaped behavior even in lecture classes, which usually
      are limited to establishing rule-governed behavior. We describe the development
      of computerized shaping simulations and the development of software that teaches
      students to discriminate among reinforcement schedules on the basis of cumulative
      records.

PMID- 22478229
TI  - Statewide behavior analysis training through distance education.
AB  - Human services and educational agencies frequently lack qualified behavior
      analysts, often because of the insufficient availability of training in behavior
      analysis. This paper describes the statewide implementation of a distance
      education-based training program to help remedy the problem.

PMID- 22478230
TI  - Developing an interdisciplinary master's program in applied behavior analysis.
AB  - At many universities, faculty interested in behavior analysis are spread across
      disciplines. This makes difficult the development of behavior-analytically
      oriented programs, and impedes regular contact among colleagues who share common
      interests. However, this separation by disciplines can be a source of strength if
      it is used to develop interdisciplinary programs. In this article we describe how
      a bottom-up strategy was used to develop two complementary interdisciplinary MS
      programs in applied behavior analysis, and conclude with a description of the
      benefits-some obvious, some surprising-that can emerge from the development of
      such programs.

PMID- 22478231
TI  - A self-capitalization model for building behavior analysis graduate programs.
AB  - The development of the Behavior Analysis Program at the University of Nevada
      through self-capitalization is described. With this model, both doctoral and
      master's degree programs were established at almost no cost to the university.
      Some of the problems encountered along the way, including gaining support for the
      original proposal, attracting and retaining high-quality faculty, engendering
      support from the Department of Psychology and the university, developing
      resources, and balancing academic with entrepreneurial demands are discussed, as
      are the solutions we have found for those problems.

PMID- 22478232
TI  - Saving the world by teaching behavior analysis: a behavioral systems approach.
AB  - This article presents a behavioral systems approach to organizational design and
      applies that approach to the teaching of behavior analysis. This systems approach
      consists of three components: goal-directed systems design, behavioral systems
      engineering, and performance management. This systems approach is applied to the
      Education Board and Teaching Behavior Analysis Special Interest Group of the
      Association for Behavior Analysis, with a conclusion that we need to emphasize
      the recruitment of students and the placement and maintenance of alumni. This
      systems approach is also applied at the scale of the individual faculty member
      running a university-based training system and is seen to generate special
      approaches to textbook preparation, undergraduate research, colloquium and
      conference attendance, career counseling, preparation for graduate examinations,
      graduate training and graduate seminars, and classroom alternatives to the
      traditional lecture.

PMID- 22478233
TI  - Toward dialogue with cognitive psychology.

PMID- 22478234
TI  - Do we need an alternative theory of verbal behavior?: a reply to Hayes and
      Wilson.

PMID- 22478235
TI  - Myths of meaning: response to Reese (1994).

PMID- 22478236
TI  - Editorial.

PMID- 22478237
TI  - A mingled yarn.
AB  - The behavior of nonliving and living systems is generally viewed as being
      qualitatively different. The key difference is often summarized by saying that
      whereas living systems are complex, nonliving ones are simple. This distinction
      is often the basis for claiming essential differences in conceptual stances,
      methods, and theories between scientific fields. I argue first that nonliving
      systems can display the unpredictable, irreducible, irreversible, and emergent-in
      sum, complex-properties of living systems. Then I discuss an emerging field
      called complexity theory, the principles of which offer the promise of bringing
      quantitative unity to an enormous range of phenomena, living or dead.

PMID- 22478238
TI  - Distinguishing between applied research and practice.
AB  - Behavior-analytic research is often viewed along a basic-applied continuum of
      research goals and methods. The applied portion of this continuum has evolved in
      ways that combine applied research and service delivery. Although these two
      facets of applied behavior analysis should be closely related, more clearly
      distinguishing between them, particularly in how we conceptualize and conduct
      applied research, may enhance the continuing development of each. This
      differentiation may improve the recruitment and training of graduate students.

PMID- 22478239
TI  - Reflections on some early events related to behavior analysis of child
      development.
AB  - A series of events related to the early application of behavioral principles to
      child behavior and development is described. The events began in the 1930s at
      Columbia University with a solicited letter from John B. Watson suggesting a
      master's degree thesis problem, and continued through the 1950s and 1960s at the
      University of Washington. Specifically, these happenings resulted in (a) research
      demonstrating that Skinner's laboratory method for studying nonhuman organisms
      could be profitably applied to the laboratory study of young normal children; (b)
      a demonstration that by successive approximations, a normal child can be
      operantly conditioned to respond to an arbitrary situation; (c) research showing
      that the effects of simple schedules of reinforcement obtained with nonhuman
      organisms could be duplicated in young normal and retarded children; (d) the
      demonstration that Skinner's operant laboratory method could be adapted to study
      young children in field situations; (e) research showing that operant principles
      can be successfully applied to the treatment of a young autistic boy with a
      serious visual handicap; (f) laboratory studies showing that mothers can be
      trained to treat their own young children who have behavior problems; (g) an in
      home study demonstrating that a mother can treat her own child who has behavior
      problems; (h) a demonstration that operant principles can be applied effectively
      to teaching reading, writing, and arithmetic to children with retardation; and
      (i) publication of a book, Child Development: A Systematic and Empirical Theory,
      in collaboration with Donald M. Baer, by Prentice Hall in their Century
      Psychological Series.

PMID- 22478240
TI  - How is physiology relevant to behavior analysis?
AB  - Physiology is an important biological science; but behavior analysis is not a
      biological science, and behavior analysts can safely ignore biological processes.
      However, ignoring products of biological processes might be a serious mistake.
      The important products include behavior, instinctive drift, behavior potentials,
      hunger, and many developmental milestones and events. Physiology deals with the
      sources of such products; behavior analysis can deal with how the products affect
      behavior, which can be understood without understanding their sources.

PMID- 22478241
TI  - On the relation between behavior analysis and biology.

PMID- 22478242
TI  - Toward a reconstructive understanding of behavior: A response to Reese.

PMID- 22478243
TI  - Reactions to Reese: Lord, let us laud and lament.

PMID- 22478244
TI  - On the invulnerability of behavior-analytic theory to biological research.

PMID- 22478245
TI  - Response to commentaries.

PMID- 22478246
TI  - Method and theory in memory; Or, how many rooms are there in the Mad Hatter's
      house?

PMID- 22478247
TI  - Mediationism and the obfuscation of memory.
AB  - Memory theorizing is going nowhere. The reason is that it is rooted in
      mediationism, the doctrine that memory is mediated by some sort of memory trace.
      Mediationism is the basic tenet of those who seek the substrate of memory; for
      students of memory per se it is merely a metaphor, and moreover an unfruitful
      one, for it cannot be penetrated by the methods of psychology. The rejection of
      mediationism would serve both to replace mechanistic theories with laws or other
      modes of explanation and to focus research on the actual experience of memory and
      on the context in which it occurs. The ensuing advantages are discussed and
      illustrated.

PMID- 22478248
TI  - Commentary on Watkins (1990): There are other solutions to the problem of
      proliferating memory theories.

PMID- 22478249
TI  - Mediationism has no place in psychology: Reply to Salthouse.

PMID- 22478251
TI  - Response to Harzem's review of modern perspectives on John B. Watson and
      classical behaviorism.

PMID- 22478250
TI  - Tempered with a harsh word: Harzem's review of modern perspectives on John B.
      Watson and classical behaviorism.

PMID- 22478252
TI  - Mechanistic ontology and contextualistic epistemology: Response to Barnes and
      Roche.

PMID- 22478253
TI  - Aberrance in science: Should behavior analysts know about psychological
      behaviorism?

PMID- 22478255
TI  - Excellent and fair.

PMID- 22478254
TI  - Response to Marr's and Zuriff's reviews of understanding behaviorism: Science,
      behavior, and culture.

PMID- 22478256
TI  - Translating the covenant: The behavior analyst as ambassador and translator.
AB  - Behavior analysts should be sensitive to how others react to and interpret our
      language because it is inextricably related to our image. Our use of conceptual
      revision, with such terms as punishment, has created communicative confusion and
      hostility on the part of general and professional audiences we have attempted to
      influence. We must, therefore, adopt the role of ambassador and translator in the
      nonbehavioral world. A number of recommendations are offered for promoting,
      translating, and disseminating behavior analysis.

PMID- 22478257
TI  - Behavioral fluency: Evolution of a new paradigm.
AB  - Behavioral fluency is that combination of accuracy plus speed of responding that
      enables competent individuals to function efficiently and effectively in their
      natural environments. Evolving from the methodology of free-operant conditioning,
      the practice of precision teaching set the stage for discoveries about relations
      between behavior frequency and specific outcomes, notably retention and
      maintenance of performance, endurance or resistance to distraction, and
      application or transfer of training. The use of frequency aims in instructional
      programming by Haughton and his associates led to formulation of empirically
      determined performance frequency ranges that define fluency. Use of fluency-based
      instructional methods has led to unprecedented gains in educational cost
      effectiveness, and has the potential for significantly improving education and
      training in general. This article traces the development of concepts, procedures,
      and findings associated with fluency and discusses their implications for
      instructional design and practice. It invites further controlled research and
      experimental analyses of phenomena that may be significant in the future
      evolution of educational technology and in the analysis of complex behavior.

PMID- 22478259
TI  - Is fluency free-operant response-response chaining?
AB  - This article briefly reviews behavioral fluency and its 10 products. Fluency
      development requires three of the four free-operant freedoms: the freedom to
      present stimuli at the learner's rhythm, the freedom to form the response, and
      the freedom to speed at the learner's maximum frequency. The article closes with
      several suggestions that fluent performing is really operant response-response (R
      R) chaining, and recommends further controlled laboratory research on free
      operant R-R chaining.

PMID- 22478258
TI  - The four free-operant freedoms.
AB  - This article reviews early free-operant conditioning laboratory research and
      applications. The seldom-mentioned four free-operant freedoms are described for
      the first time in detail. Most current behavior analysts do not realize that the
      freedom to form responses and the freedom to speed responses were crucial steps
      in designing free-operant operanda in the 1950s. These four freedoms were known
      by the laboratory researchers of the 1950s to the point that, along with operanda
      design, Sidman (1960) did not feel the need to detail them in his classic,
      Tactics of Scientific Research. The dimensions of freedom in the operant were so
      well understood and accepted in the 1950s that most thought it redundant to use
      the term free operant. These issues are reviewed in some detail for younger
      behavior analysts who did not have the opportunity of learning them firsthand.

PMID- 22478260
TI  - Twenty years of applied behavior analysis in treating the most severe problem
      behavior: Lessons learned.
AB  - This paper reviews some of the author's experiences during the past 20 years of
      treating severe problem behavior. Factors that represent barriers to success are
      identified and discussed, as are factors that contribute to the development of
      successful treatment programs. Barriers to success include the inherent reactive
      nature of human services and educational systems, expertise problems, systems
      problems, information gaps, programming problems, characteristics of problem
      behavior, and maintenance problems. Some new programmatic directions are
      suggested for overcoming the various treatment barriers. The paper concludes with
      strategies and factors to consider that will ensure long-term success in the
      treatment of severe problem behavior.

PMID- 22478261
TI  - The differential effects of tangible rewards and praise on intrinsic motivation:
      A comparison of cognitive evaluation theory and operant theory.
AB  - Substantial research indicates that tangible rewards, such as money, prizes, and
      tokens, decrease response rates by undermining intrinsic motivation. In contrast,
      praise appears to increase response rates by enhancing intrinsic motivation.
      Based on their interpretation of available evidence, many social-cognitive
      researchers warn not to use tangible rewards in applied settings and to use
      praise instead. Furthermore, they suggest that the differential effects of the
      two types of rewards on intrinsic motivation cannot be explained using principles
      of operant psychology. Cognitive evaluation theory provides one of the most
      recent and widely cited social-cognitive explanations for the different effects
      of the two types of rewards on intrinsic motivation (Deci & Ryan, 1985). However,
      a review of existing research found little support for the explanations based on
      this theory and revealed three potential confounding effects: (a) temporal
      contiguity, (b) the number of reward administrations, and (c) discriminative
      stimuli associated with reward availability. These three confounding factors
      provide explanations for the effects of tangible rewards and praise on intrinsic
      motivation that are consistent with principles of operant psychology.

PMID- 22478262
TI  - Envisioning cultural practices.
AB  - Graphic visualization has demonstrated its value for organizing transactional
      data and modeling complex phenomena in a wide variety of fields, from theoretical
      physics to medicine. Behavior analysts have historically used a variety of
      graphic tools not only for presentation but also for analysis and teaching. As
      they turn increasingly to the analysis and design of cultural practices, the
      phenomena behavior analysts study are becoming increasingly complicated. Many
      cultural practices of interest are embedded in extensive webs of interlocking
      practices and contingencies that can be difficult to grasp comprehensively.
      Building on contingency diagrams, which have proven to be useful for the analysis
      of operant behavior, and graphic tools developed for object-oriented systems
      analysis, this paper suggests graphic tools for capturing the interlocking
      contingencies that constitute cultures. These diagrams offer a broad-bandwidth
      technology for analyzing and designing cultural practices.

PMID- 22478263
TI  - Why be moral: Humanist and behavioral perspectives.
AB  - Students of philosophy have struggled with the question, "Why should I be moral?"
      Many diverse theorists have constructed elaborate logical arguments that explain
      why people in general should behave morally, but have had difficulty explaining
      why any given individual, safe from detection or retribution, should behave in a
      moral fashion. To avoid this problem, the notion of a supernatural deity (one who
      is always watching and thus removes the notion of nondetection and
      nonretribution) has been introduced by numerous thinkers. Philosophical systems
      that pride themselves on being based only on natural phenomena, however, can make
      no such recourse (leading to the charge, particularly from the religious, that
      without a god concept there can be no morality). Naturalistic humanists and
      behavior analysts are two groups who have found themselves unable to invoke a
      deity and thus face the question "Why should I behave morally?" Parallel attempts
      from both camps will be described and analyzed, with the conclusion being drawn
      that although such naturalists may not be better off than their more religious
      friends, they are certainly no worse off.

PMID- 22478265
TI  - Overlearning, fluency, and automaticity.

PMID- 22478264
TI  - On terms and procedures: Fluency.
AB  - Fluency is a metaphor for flowing, effortless, well-practiced, and accurate
      performance. Current practice in fluency building involves increasing the
      frequency of free-operant performances. Free-operant performance is defined as
      continuous responding in the presence of discriminative stimuli that are either
      varied or not varied from response to response. Free-operant performance is also
      distinguished from discrete-trial performance. Frequency-building procedures are
      also described, including defining the learning channel and stimulus control
      topography of a component performance (called a pinpoint), selecting an
      appropriate timing period, and displaying stimuli so that no performance ceilings
      occur. During frequency building, frequencies of pinpoints are continuously
      charted on standard celeration charts. Frequencies are increased to empirically
      derived performance standards, or aims, that predict retention, endurance,
      stability, application, and adduction of performance. Frequency is also described
      as a dimension of performance, not simply its measurement. Frequency building is
      described as possibly facilitating contingency adduction.

PMID- 22478266
TI  - Prediction and control in Loeb's visualization and Skinner's contingencies:
      Response to Hackenberg.

PMID- 22478268
TI  - Certification of behavior analysts in Minnesota.

PMID- 22478267
TI  - When being a mechanist wasn't so bad: Reply to Moxley.

PMID- 22478269
TI  - Editorial.

PMID- 22478270
TI  - Applied behavior analysis, service and the acquisition of knowledge.

PMID- 22478272
TI  - A reply to Dinsmoor.

PMID- 22478271
TI  - A note on the historical record: MPA and MABA.

PMID- 22478273
TI  - On the relation between generalization and generality.

PMID- 22478274
TI  - Editorial.

PMID- 22478275
TI  - Ethics for behaviorists.

PMID- 22478276
TI  - Behavior mod: A short reply to the critics.

PMID- 22478277
TI  - Behavioral assessment of human preference.

PMID- 22478278
TI  - Editorial.

PMID- 22478280
TI  - The alleged vices of popularization and the potential vices of laboratory
      isolation.

PMID- 22478279
TI  - Is a new definition of verbal behavior necessary in light of derived relational
      responding?

PMID- 22478281
TI  - A belated response to Moxley.

PMID- 22478282
TI  - A renaissance in residential behavior analysis? A historical perspective and a
      better way to help people with challenging behavior.
AB  - After a slow start, the popularity of applied behavior analysis for people with
      severe behavior problems peaked in the 1970s and was then battered down by the
      effects of methodological behaviorism, the aversives controversy, overregulation,
      and the inherent limitations of congregate living. Despite the ethical,
      technical, and conceptual advancements in behavior analysis, many people with
      challenging behavior live in futile environments in which the behavior analyst
      can only tinker. A radically behavioristic approach has become available that has
      the power to change these conditions, to restore the reciprocity necessary for
      new learning, and to bring residential behavior analysts more in contact with the
      contingencies of helping and teaching. The approach is consistent with
      alternatives that behaviorists have suggested for years to improve the image and
      effectiveness of applied behavior analysis, although it will take the behaviorist
      far from the usual patterns of practice. Finally, the approach promotes its own
      survival by promoting access to interlocking organizational contingencies, but
      its antithetical nature presents many conceptual and practical challenges to
      agency adoption.

PMID- 22478283
TI  - Behavior analysis and farm animal welfare.
AB  - This article demonstrates that there is a role for behavior-analytic techniques
      in the area of farm animal welfare and provides examples of the kinds of work
      that can be done. Behavior-analytic procedures, specifically those used in the
      study of psychophysics, preference, and demand, can provide answers to three
      questions people concerned with the welfare of farm animals are likely to ask:
      What can the animals detect? What do they like and dislike? What will they work
      to attain or preserve? Such information certainly is necessary for making
      reasonable decisions about animal welfare, although it is not sufficient in and
      of itself.

PMID- 22478284
TI  - Making behavioral technology transferable.
AB  - The paucity of transferred behavioral technologies is traced to the absence of
      strategies for developing technology that is transferable, as distinct from
      strategies for conducting research, whether basic or applied. In the field of
      engineering, the results of basic research are transformed to candidate
      technologies that meet standardized criteria with respect to three properties:
      quantification, repetition, and verification. The technology of vitrification and
      storage of nuclear waste is used to illustrate the application of these criteria.
      Examples from behavior analysis are provided, together with suggestions regarding
      changes in practice that will accelerate the development and application of
      behavioral technologies.

PMID- 22478285
TI  - International publication trends in the experimental analysis of behavior.
AB  - The present paper assessed international publication trends in the experimental
      analysis of behavior by recording the geographical origin of the first authors of
      articles in the Journal of the Experimental Analysis of Behavior (JEAB), the
      Journal of Applied Behavior Analysis (JABA), and The Behavior Analyst (TBA). Five
      international categories were identified: Australasia, Europe, Latin America, the
      Middle East, and North America. A cooperative category was also employed to
      assess the number of publications with authors from different international
      categories. First, the percentage and number of international articles published
      in JEAB, JABA, and TBA are presented. Second, a more detailed analysis of the
      publication rates within the international categories is presented. The number
      and rate at which new authors from the categories appeared and the percentage of
      articles published by different authors are also presented. Some limitations of
      the review and suggestions for increasing international participation in behavior
      analysis are outlined.

PMID- 22478286
TI  - The response-stimulus contingency and reinforcement learning as a context for
      considering two non-behavior-analytic views of contingency learning.
AB  - This paper introduces a special section on the contingency. Bower and Watson were
      invited to present their views of contingency learning in human infants from
      outside the context of behavior analysis, and Cigales, Marr, and Lattal and
      Shahan provided commentaries that point out some of the more interesting and
      controversial aspects of those views from a behavior-analytic perspective. The
      debate turns on how to conceptualize the response-stimulus contingency of operant
      learning. The present paper introduces the contingency concept and contingency
      detection by subjects, as well as research practices in behavior analysis, in a
      context in which the dependency between infant responding and the presentation of
      environmental consequences may be disrupted through procedures in which
      ordinarily consequent events occur before the response or in its absence. These
      points can relate to and serve as an introduction to the Bower and Watson papers
      on infant contingency learning as well as to the three commentaries that follow.

PMID- 22478287
TI  - Contingency and its two indices within conditional probability analysis.
AB  - FOUR THEORETICAL BASES FOR DETECTING A CONTINGENCY BETWEEN BEHAVIOR AND
      CONSEQUENT STIMULI ARE CONSIDERED: contiguity, correlation, conditional
      probability, and logical implication. It is argued that conditional probability
      analysis is statistically the most powerful of these options, in part due to its
      provision of two indices of contingency: a forward time probability that
      reinforcement follows behavior and a backward time probability that behavior
      precedes reinforcement. Evidence is cited that both indices appear to bear on the
      learning of a variety of animals, although they are unequally salient to human
      adults and to artificial neural networks designed to solve time-series functions.
      It is hypothesized that humans may acquire the capacity to detect contingency in
      the progressive sequence: contiguity, correlation, forward time conditional
      probability, backward time conditional probability, and ultimately logical
      implication.

PMID- 22478288
TI  - Contingencies, logic, and learning.
AB  - A logical analysis of operant learning is presented. In total, the analysis makes
      a number of predictions that are different from the predictions of any other
      theory. Individual predictions can be explained by other theories, but the
      pattern of predictions is unique. Some tests of the predictions of the analysis
      with human newborns are described. The analysis predicts increased variance in
      sucking with the introduction of continuous reinforcement. This does occur. The
      analysis predicts a decreased rate of sucking with a shift from continuous to
      partial reinforcement. This does occur. The analysis predicts an increased rate
      of sucking with a shift from continuous reinforcement to continuous plus
      noncontingent reinforcement. Due to methodological deficiencies, we have been
      unable to test this prediction. However, it has been confirmed by others. The
      most exciting prediction of the analysis is a rapid way of producing extinction.
      That has not been tested with newborns; however, there is confirmatory evidence
      in the literature.

PMID- 22478289
TI  - Differing views of contingencies: How contiguous?
AB  - The contingency between environmental events and behavior has proven to be a
      useful concept in the study of both behavior and cognition. There is common
      ground in the definition of contingency in both domains, but interpretations of
      the basis of its action differ. For behavior analysts the contingency acts
      through both its direct, response-strengthening effect and indirectly through its
      function as a discriminative stimulus. Cognitive accounts, as represented in the
      work of both Bower and Watson, focus more on the organism's detection and
      interpretation of the contingency as the basis of its action. Despite such
      conceptual differences, Watson's quantitative descriptions of contingency effects
      seem relevant to feedback functions that describe reinforcement schedule
      performance and, as such, may bear on research involving combinations of response
      dependent and response-independent food presentations and on superstitious
      behavior.

PMID- 22478290
TI  - Infants' feats of inference: A commentary on Bower and Watson.

PMID- 22478291
TI  - Intersections of behavior analysis with cognitive models of contingency
      detection.
AB  - Bower and Watson have offered, respectively, a logical hypothesis-testing model
      and a conditional probability model of contingency detection by young infants.
      Although each could represent cognitive processes concomitant with operant
      learning, empirical support for these models is sparse. The limitations of each
      model are discussed, and suggestions are made for a more parsimonious approach by
      focusing on the areas of overlap between the two.

PMID- 22478293
TI  - A behaviorological thanatology: Foundations and implications.
AB  - Foundation principles supporting a behaviorological thanatology are reviewed,
      including concepts of life, person, death, value, right, ethic, and body/person
      distinctions. These natural science foundations are contrasted with traditional
      foundations, and their respective implications are speculatively explored.

PMID- 22478292
TI  - Making sense of sensitivity in the human operant literature.
AB  - Human operant behavior is often said to be controlled by different variables or
      governed by different processes than nonhuman operant behavior. Support for this
      claim within the operant literature comes from data suggesting that human
      behavior is often insensitive to schedules of reinforcement to which nonhuman
      behavior has been sensitive. The data that evoke the use of the terms sensitivity
      and insensitivity, however, result from both between-species and within-subject
      comparisons. We argue that because sensitivity is synonymous with experimental
      control, conclusions about sensitivity are best demonstrated through within
      subject comparisons. Further, we argue that even when sensitivity is assessed
      using within-subject comparisons of performance on different schedules of
      reinforcement, procedural differences between studies of different species may
      affect schedule performance in important ways. We extend this argument to age
      differences as well. We conclude that differences across populations are an
      occasion for more precise experimental analyses and that it is premature to
      conclude that human behavior is controlled by different processes than nonhuman
      behavior.

PMID- 22478294
TI  - Dying slowly with compassion and dignity: A commentary.
AB  - Fraley offers a provocative behavior-analytic perspective on the process of slow
      death. I argue that the value of his insightful analysis is severely compromised
      by his insistence on equating behavioral competence with personal worth. Fraley
      errs by proclaiming that his philosophy is science, that existing social
      practices are essential human attributes, and that idiosyncratic reinforcing
      stimuli are universally functional. Further, his philosophical tenet is
      fundamentally inconsistent with his genuinely humane goal of understanding and
      promoting protracted dying as a behavioral rather than metaphysical phenomenon.

PMID- 22478295
TI  - Beyond equality: A reply to Rakos.

PMID- 22478296
TI  - The experimental analysis of human sexual arousal: Some recent developments.
AB  - Experimental analyses of human sexual arousal have been decidedly sparse. Recent
      developments in the analysis of derived relational responding, however, have
      opened the way for a modern behavior-analytic treatment of complex or "novel"
      human behavior, including specific instances of human sexual arousal. The current
      article examines some of these developments and their relevance to the analysis
      of emotional behavior, with a focus on sexual arousal. Recent research that has
      examined the acquisition of sexual stimulus functions within a relational frame
      paradigm is then outlined. Finally, a series of relational frame interpretations
      of a variety of human sexual arousal phenomena is offered.

PMID- 22478297
TI  - Religious behaviors as strategies for organizing groups of people: A social
      contingency analysis.
AB  - A social contingency analysis of religion is presented, arguing that individual
      religious behaviors are principally maintained by the many powerful benefits of
      participating in social groups rather than by any immediate or obvious
      consequences of the religious behaviors. Six common strategies are outlined that
      can shape the behaviors of large groups of people. More specifically, religious
      behavior is shaped and maintained by making already-existing contingencies
      contingent upon low-probability, but socially beneficial, group behaviors. Many
      specific examples of religious themes are then analyzed in terms of these common
      strategies for social shaping, including taboos, rituals, totems, personal
      religious crises, and symbolic expression. For example, a common view is that
      people are anxious about life, death, and the unknown, and that the direct
      function of religious behaviors is to provide escape from such anxiety. Such an
      explanation is instead reversed-that any such anxiety is utilized or created by
      groups through having escape contingent upon members performing less probable
      behaviors that nonetheless provide important benefits to most individual group
      members. These generalized beneficial outcomes, rather than escape from anxiety,
      maintain the religious behaviors and this fits with observations that religions
      typically act to increase anxiety rather than to reduce it. An implication of
      this theory is that there is no difference in principle between religious and
      nonreligious social control, and it is demonstrated that the same social
      strategies are utilized in both contexts, although religion has been the more
      historically important form of social control.

PMID- 22478298
TI  - Why Skinner is difficult.
AB  - Skinner's views are commonly misrepresented. One reason for this difficulty is
      that changes in the way that Skinner formulated his views occurred in a gradual
      evolution over time throughout Skinner's career, and the changes and their
      significance were not as conspicuously marked as they might have been. Among
      these changes were a movement from a two-term necessity to a three-term
      contingency; a movement from discriminative stimulus to setting as the first term
      in his three-term contingency; and a movement from determinism to random
      variation as a foundational principle in his selectionist behaviorism. When not
      seen in their historical development over time, a sample reading of Skinner's
      views may readily result in misleading or inaccurate interpretations,
      particularly in respect to his later work. Seen in historical context, however,
      the accounts that survived after the changes Skinner made are well integrated in
      a selectionist theory of behavior.

PMID- 22478299
TI  - On Skinner's rejection of S-R psychology.

PMID- 22478300
TI  - Skinner may be difficult, but..

PMID- 22478301
TI  - Interpreting the record in context.

PMID- 22478302
TI  - Reply to palmer, schaal, and chiesa.

PMID- 22478303
TI  - Visual inspection of data revisited: Do the eyes still have it?
AB  - In behavior analysis, visual inspection of graphic information is the standard by
      which data are evaluated. Efforts to supplement visual inspection using
      inferential statistical procedures to assess intervention effects (e.g., analysis
      of variance or time-series analysis) have met with opposition. However, when
      serial dependence is present in the data, the use of visual inspection by itself
      may prove to be problematic. Previously published reports demonstrate that
      autocorrelated data influence trained observers' ability to identify level
      treatment effects and trends that occur in the intervention phase of experiments.
      In this report, four recent studies are presented in which autoregressive
      equations were used to produce point-to-point functions to simulate experimental
      data. In each study, various parameters were manipulated to assess trained
      observers' responses to changes in point-to-point functions from the baseline
      condition to intervention. Level shifts over baseline behavior (treatment
      effect), as well as no change from baseline (no treatment effect or trend), were
      most readily identified by observers, but trends were rarely recognized.
      Furthermore, other factors previously thought to augment and improve observers'
      responses had no impact. Results are discussed in terms of the use of visual
      inspection and the training of behavior analysts.

PMID- 22478304
TI  - A critique of the usefulness of inferential statistics in applied behavior
      analysis.
AB  - Researchers continue to recommend that applied behavior analysts use inferential
      statistics in making decisions about effects of independent variables on
      dependent variables. In many other approaches to behavioral science, inferential
      statistics are the primary means for deciding the importance of effects. Several
      possible uses of inferential statistics are considered. Rather than being an
      objective means for making decisions about effects, as is often claimed,
      inferential statistics are shown to be subjective. It is argued that the use of
      inferential statistics adds nothing to the complex and admittedly subjective
      nonstatistical methods that are often employed in applied behavior analysis.
      Attacks on inferential statistics that are being made, perhaps with increasing
      frequency, by those who are not behavior analysts, are discussed. These attackers
      are calling for banning the use of inferential statistics in research
      publications and commonly recommend that behavioral scientists should switch to
      using statistics aimed at interval estimation or the method of confidence
      intervals. Interval estimation is shown to be contrary to the fundamental
      assumption of behavior analysis that only individuals behave. It is recommended
      that authors who wish to publish the results of inferential statistics be asked
      to justify them as a means for helping us to identify any ways in which they may
      be useful.

PMID- 22478305
TI  - Editorial.

PMID- 22478306
TI  - Personal agency in feminist theory: Evicting the illusive dweller.
AB  - The growing impact of feminist scholarship, activism, and politics would benefit
      substantially from input by radical behaviorists. The feminist community, broadly
      defined, and radical behaviorists share interesting commonalities that suggest a
      potentially fruitful alliance. There are, however, points of divergence that must
      be addressed; most prominently, the construct of personal agency. A behavioral
      reconstruction of personal agency is offered to deal with the invisible
      contingencies leading to gender-asymmetric interpretive repertoires. The benefits
      of a mutually informing fusion are discussed.

PMID- 22478307
TI  - Women in the experimental analysis of behavior.
AB  - We examined the status of women in the experimental analysis of behavior by
      comparing authorship by women in the Journal of the Experimental Analysis of
      Behavior (JEAB) to authorship by women in three similar journals. For all
      journals, the percentage of articles with at least one female author, the
      percentage of authors who are female, and the percentage of articles with a
      female first author increased from 1978 to 1997. However, the participation by
      women in JEAB lagged behind participation in the other journals on each measure.
      Female membership on the editorial board of JEAB also failed to increase from
      1978 to 1997. Suggestions are made that may increase the participation of women
      in the experimental analysis of behavior.

PMID- 22478308
TI  - Judgment and decision making: Behavioral approaches.
AB  - The area of judgment and decision making has given rise to the study of many
      interesting phenomena, including reasoning fallacies, which are also of interest
      to behavior analysts. Indeed, techniques and principles of behavior analysis may
      be applied to study these fallacies. This article reviews research from a
      behavioral perspective that suggests that humans are not the information-seekers
      we sometimes suppose ourselves to be. Nor do we utilize information effectively
      when it is presented. This is shown from the results of research utilizing
      matching to sample and other behavioral tools (monetary reward, feedback,
      instructional control) to study phenomena such as the conjunction fallacy, base
      rate neglect, and probability matching. Research from a behavioral perspective
      can complement research from other perspectives in furthering our understanding
      of judgment and decision making.

PMID- 22478309
TI  - Experimental design: Problems in understanding the dynamical behavior-environment
      system.
AB  - In this paper, I attempt to describe the implications of dynamical approaches to
      science for research in the experimental study of behavior. I discuss the
      differences between classical and dynamical science, and focus on how dynamical
      science might see replication differently from classical science. Focusing on
      replication specifically, I present some problems that the classical approach has
      in dealing with dynamics and multiple causation. I ask about the status and
      meaning of "error" variance, and whether it may be a potent source of
      information. I show how a dynamical approach can handle the sort of control by
      past events that is hard for classical science to understand. These concerns
      require, I believe, an approach to variability that is quite different from the
      one most researchers currently employ. I suggest that some of these problems can
      be overcome by a notion of "behavioral state," which is a distillation of an
      organism's history.

PMID- 22478310
TI  - Behavioral history: A definition and some common findings from two areas of
      research.
AB  - Behavioral history research includes studies that (a) permit assessment of a
      prior experimental condition on a subsequent one, (b) show either short-lived or
      permanent effects, and (c) produce effects that are observable in ongoing
      behavior or that may be unobservable until special test conditions are
      introduced. We review experiments within both the conventional experimental
      analysis of behavior and behavioral pharmacology in order to identify
      commonalities and differences in the outcomes of conceptually similar
      experiments. We suggest that a deeper understanding of the necessary and
      sufficient conditions for producing history effects will emerge from these
      complementary research efforts.

PMID- 22478311
TI  - Moral behavior and the development of verbal regulation.
AB  - The present paper examines the relationship between the development of moral
      behavior and the development of verbal regulatory processes. Relational frame
      theory and the distinctions among pliance, tracking, and augmenting forms of rule
      governance are applied to the domain of moral behavior and its development, in
      order to identify the specific social and verbal contingencies that are
      responsible for an evolving moral repertoire. It is argued that moral behavior is
      controlled by relational and rule-following repertoires, and that these can be
      arranged into a rough progression: pliance, tracking, augmenting, social concern
      for pliance, social concern for tracking, and social concern for augmenting.
      Congruence with data derived from other research traditions is examined, and
      applied implications are explored.

PMID- 22478312
TI  - The introductory class in higher education: Some old problems and new
      considerations.
AB  - The traditional text and lecture format has remained the norm in introductory
      college courses despite evidence, such as the personalized system of instruction,
      that other practices could improve what is learned and retained. The growth of
      distance learning provides new opportunities to implement effective teaching
      practices. Unfortunately, an adequate comparison of various teaching practices is
      not possible (even with regard to the teaching of behavior analysis). Few
      practices have been assessed with respect to course-end effects (final exam
      performance), and longer term effects remain almost wholly unexplored. Studies of
      the retention of academic materials, the practice required for mastery or
      fluency, and the relation between verbal repertoires and correspondent everyday
      behaviors suggest course outcomes more modest than those hoped for earlier.
      Suggestions for changing current practices have little credibility until the size
      of the gap between present and possible learning outcomes is much better known,
      and the personal, social, and economic consequences of bridging that gap (or not)
      are assessed.

PMID- 22478313
TI  - Adverse implications for university teaching concealed in economically driven
      policies.
AB  - Modern universities represent large economic operations fueled by funds that are
      increasingly derived from student tuition as government subsidies shrink. Student
      recruitment and retention are now mainly driven by the need for the dollars that
      students pay into the system. Policy that is responsive to these pressing
      economic realities, promulgated at all institutional levels, promotes
      professional behavior that encourages student retention while allowing this to
      occur through subtle sacrifice of the traditional essence of the university. A
      multiphase analysis relates the institution's economically driven policies on
      retention to their classroom implications and to other effects on the behavior of
      the teaching faculty.

PMID- 22478314
TI  - Epistemological barriers to radical behaviorism.
AB  - The historian and philosopher of science Gaston Bachelard proposed the concept of
      epistemological barriers to describe the intellectual challenges encountered by
      scientists in their work. In order to embrace novel ways of approaching a problem
      in science, scientists must overcome barriers or obstacles posed by their prior
      views. For example, Einsteinian physics presents scientists with claims that
      space is curved and that time and space are on the same continuum. We utilize
      Bachelard's concept of epistemological barriers to describe the differences
      between the intellectual journeys students pursuing advanced studies face when
      attempting to accept cognitive psychology or radical behaviorism. We contend that
      the folk psychological beliefs that students typically hold when entering these
      studies pose less challenge to cognitive psychology than to radical behaviorism.
      We also suggest that these barriers may also partly be involved in the
      problematic exegesis that has plagued radical behaviorism. In close, we offer
      some suggestions for dealing with these epistemological barriers.

PMID- 22478315
TI  - Radical behaviorist interpretation: Generating and evaluating an account of
      consumer behavior.
AB  - This article considers an approach to the radical behaviorist interpretation of
      complex human social behavior. The chosen context is consumer psychology, a field
      currently dominated by cognitive models of purchase and consumption. The nature
      of operant interpretation is considered, and several levels of operant analysis
      of complex economic behavior in affluent marketing-oriented economies are
      developed. Empirical evidence for the interpretation is considered, and a case is
      made for the qualified use of the hypothetico-deductive method in the appraisal
      of operant interpretations of complex behaviors.

PMID- 22478316
TI  - Editorial.

PMID- 22478317
TI  - Is the learn unit a fundamental measure of pedagogy?
AB  - We propose a measure of teaching, the learn unit, that explicitly describes the
      interaction between teachers and their students. The theoretical, educational
      research, and applied behavior analysis literatures all converge on the learn
      unit as a fundamental measure of teaching. The theoretical literature proposes
      the construct of the interlocking operant and embraces verbal behavior, social
      interaction, and translations of psychological constructs into complex
      theoretical respondent-operant interactions and behavior-behavior relations.
      Research findings in education and applied behavior analysis on engaged academic
      time, opportunity to respond, active student responding, teacher-student
      responding, student-teacher responding, tutor-tutee responding, tutee-tutor
      responding, and verbal episodes between individuals all support a measure of
      interlocking responses. More recently, research analyzing the components of both
      the students' and teachers' behavior suggests that the learn unit is the
      strongest predictor of effective teaching. Finally, we propose applications of
      the learn unit to other issues in pedagogy not yet researched and the relation of
      learn units to the verbal behavior of students.

PMID- 22478318
TI  - Clinical behavior analysis and clinical social work: A mutually reinforcing
      relationship.
AB  - Clinical behavior analysis (CBA) and clinical social work (CSW) have the
      potential to gain much from one another. The existing synergistic relation
      between the fields, however, is largely under-recognized, overwhelmed by the
      stronger disciplinary and historical associations among behavior analysis and
      psychology and education. This paper reviews the similarities and differences
      between CBA and CSW, how they have enriched each other, and the potential for
      greatly expanded relations between the two fields.

PMID- 22478319
TI  - Human sensitivity to reinforcement: A comment on Kollins, Newland, and
      Critchfield's (1997) quantitative literature review.
AB  - In a quantitative review of human operant experiments, Kollins, Newland, and
      Critchfield (1997) found that humans are less sensitive to reinforcement
      contingencies than nonhumans are. Human performances were not as consistent with
      the matching law, and they were more variable from subject to subject. Some of
      the variables correlated with reduced human sensitivity were surprising. These
      included collection of the data under more controlled conditions (laboratory
      rather than naturalistic settings), and inclusions of discriminative stimuli
      correlated with alternative sources of reinforcement. We discuss these unexpected
      findings in the light of criticisms that have been leveled against meta-analytic
      literature reviews (e.g., the wisdom of grouping studies with widely diverse
      methods), and we suggest ways of improving future analyses of the behavior
      analytic literature.

PMID- 22478320
TI  - Comments on the learn unit.

PMID- 22478321
TI  - Renaissance or killer mutation? A response to Holburn.

PMID- 22478322
TI  - Further comments on person-centered approaches.

PMID- 22478323
TI  - Statistical inference in behavior analysis: Friend or foe?
AB  - Behavior analysts are undecided about the proper role to be played by inferential
      statistics in behavioral research. The traditional view, as expressed in Sidman's
      Tactics of Scientific Research (1960), was that inferential statistics has no
      place within a science that focuses on the steady-state behavior of individual
      organisms. Despite this admonition, there have been steady inroads of statistical
      techniques into behavior analysis since then, as evidenced by publications in the
      Journal of the Experimental Analysis of Behavior. The issues raised by these
      developments were considered at a panel held at the 24th annual convention of the
      Association for Behavior Analysis, Orlando, Florida (May, 1998). The proceedings
      are reported in this and the following articles.

PMID- 22478324
TI  - Statistical inference in behavior analysis: Some things significance testing does
      and does not do.
AB  - Significance testing plays a prominent role in behavioral science, but its value
      is frequently overestimated. It does not estimate the reliability of a finding,
      it does not yield a probability that results are due to chance, nor does it
      usually answer an important question. In behavioral science it can limit the
      reasons for doing experiments, reduce scientific responsibility, and emphasize
      population parameters at the expense of behavior. It can, and usually does, lead
      to a poor approach to theory testing, and it can also, in behavior-analytic
      experiments, discount reliability of data. At best, statistical significance is
      an ancillary aspect of a set of data, and therefore should play a relatively
      minor role in advancing a science of behavior.

PMID- 22478325
TI  - Statistical inference in behavior analysis: Environmental determinants?
AB  - Use of inferential statistics should be based on the experimental question, the
      nature of the design, and the nature of the data. A hallmark of single-subject
      designs is that such statistics should not be required to determine whether the
      data answer the experimental question. Yet inferential statistics are being
      included more often in papers that purport to present data relevant to the
      behavior of individual organisms. The reasons for this too often seem to be
      extrinsic to the experimental analysis of behavior. They include lapses in
      experimental design and social pressure from colleagues who are unfamiliar with
      single-subject research. Regardless of whether inferential statistics are used,
      behavior analysts need to be sophisticated about experimental design and
      inferential statistics. Such sophistication not only will enhance design and
      analysis of behavioral experiments, but also will make behavior analysts more
      persuasive in presenting rationales for the use or nonuse of inferential
      statistics to the larger scientific community.

PMID- 22478326
TI  - Statistical inference in behavior analysis: Having my cake and eating it?
AB  - Using simple, nonparametric statistical procedures can formalize the process of
      letting data speak for themselves, and can eliminate the gratuitous dismissal of
      deviant data from subjects or conditions. These procedures can act as useful
      discriminative stimuli, both for behavior analysts and for those from other areas
      of psychology who occasionally sample our journals. I also argue that changes in
      publication policies must change if behavior analysts are to accurately
      discriminate between real, reliable effects (hits) and false alarms.

PMID- 22478327
TI  - Statistical inference in behavior analysis: Useful friend.
AB  - Single-subject and statistical inference are virtually identical. With both
      techniques change is inferred when variability across conditions is sufficiently
      large to accommodate variability within conditions, replication is the final
      arbiter of whether change is likely to occur by chance, a large effect size is
      preferred to a small consistent difference, there are similar threats to internal
      validity, and generalizability of results is valued. Knowing how to use
      statistical inferential procedures would make behavior analysts more
      methodologically sophisticated. It would also help them to critically evaluate
      research in other areas of psychology, obtain research grants, and publish their
      research in diverse outlets, which would help others to see behavior-analytic
      work.

PMID- 22478328
TI  - Statistical inference in behavior analysis: Experimental control is better.
AB  - Statistical inference promises automatic, objective, reliable assessments of
      data, independent of the skills or biases of the investigator, whereas the single
      subject methods favored by behavior analysts often are said to rely too much on
      the investigator's subjective impressions, particularly in the visual analysis of
      data. In fact, conventional statistical methods are difficult to apply correctly,
      even by experts, and the underlying logic of null-hypothesis testing has drawn
      criticism since its inception. By comparison, single-subject methods foster
      direct, continuous interaction between investigator and subject and development
      of strong forms of experimental control that obviate the need for statistical
      inference. Treatment effects are demonstrated in experimental designs that
      incorporate replication within and between subjects, and the visual analysis of
      data is adequate when integrated into such designs. Thus, single-subject methods
      are ideal for shaping-and maintaining-the kind of experimental practices that
      will ensure the continued success of behavior analysis.

PMID- 22478329
TI  - Statistical inference in behavior analysis: Discussant's remarks.
AB  - A collection of essays on the roles of inferential statistics in behavior
      analytic research prompted consideration of five issues: (a) the acceptance of
      research that focuses on the behavior of individual organisms; (b) the need to
      apply methods thoughtfully; (c) the heuristic value of statistical description;
      (d) the treatment of aberrant data in the search for general principles; and (e)
      the role of derived measures in the search for invariances.

PMID- 22478330
TI  - An interview with W. N. Schoenfeld (july 22, 1990).
AB  - This article is a transcription of an interview with William N. Schoenfeld made
      in 1990. William N. Schoenfeld (1915-1996) is one of the outstanding contributors
      to the initial stages of the experimental analysis of behavior. After graduating
      from Columbia University, Schoenfeld wrote, in collaboration with Fred S. Keller,
      what was at that time the most significant book introducing, and updating, the
      seminal contributions of B. F. Skinner and other behavioral psychologists:
      Principles of Psychology (1950). Schoenfeld was also instrumental in the design
      of a psychology course at Columbia University based on the integration of theory
      and laboratory work, as well as in the foundation of the Journal of the
      Experimental Analysis of Behavior in 1958. In 1968 Schoenfeld moved to the Queens
      College of the City University of New York, where he developed a doctoral program
      based in the research of stimulus schedules (T system), the analysis of
      conceptual and theoretical problems in operant conditioning, and the study of
      respondent and operant interactions under pharmacological agents. After his
      retirement from Queens College, Schoenfeld taught at Bar-Ilan University and the
      Hebrew University in Israel. The interview forms part of a research project on
      the experimental analysis of scientific behavior (Ribes, 1994), which also
      included two other distinguished and original contributors of the experimental
      analysis of behavior, B. F. Skinner and R. J. Herrnstein.

PMID- 22478331
TI  - H. G. Wells and B. F. Skinner on the superorganism.
AB  - In Skinner's Walden Two, the central character Frazier refers to the
      superorganism and how to build it, but without elaboration. An examination of
      some parallels between the work of H. G. Wells and B. F. Skinner, however, casts
      light on that reference and other aspects of Skinner's views, such as multiple
      selves. Both Wells and Skinner wrote in similar ways about what the composition
      of such a superorganism would be and the conditions for its development. In
      particular, attention is directed to the ways in which their forecasts of the
      conditions for producing the superorganism changed over time, from determinism
      based conditions to more evolutionary or selection-based conditions.

PMID- 22478332
TI  - Quantitative integration of single-subject studies: Methods and
      misinterpretations.
AB  - Derenne and Baron (1999) criticized a quantitative literature review by Kollins,
      Newland, and Critchfield (1997) and raised several important issues with respect
      to the integration of single-subject data. In their criticism they argued that
      the quantitative integration of data across experiments conducted by Kollins et
      al. is a meta-analysis and, as such, is inappropriate. We reply that Kollins et
      al. offered behavior analysts a technique for integrating quantitative
      information in a way that draws from the strengths of behavior analysis. Although
      the quantitative technique is true to the original spirit of meta-analysis, it
      bears little resemblance to meta-analyses as currently conducted or defined and
      offers behavior analysts a potentially useful tool for comparing data from
      multiple sources. We also argue that other criticisms raised by Derenne and Baron
      were inaccurate or irrelevant to the original article. Our response highlights
      two main points: (a) There are meaningful quantitative techniques for examining
      single-subject data across studies without compromising the integrity of behavior
      analysis; and (b) the healthiest way to refute or question findings in any viable
      field of scientific inquiry is through empirical investigation.

PMID- 22478333
TI  - Clinical behavior analysis and clinical social work: A mutually reinforcing
      relationship (as long as science is included).

PMID- 22478334
TI  - Private events: Do they belong in a science of human behavior?
AB  - The role of thinking, feeling, and other private events has received a great deal
      of attention in mainstream psychology but has been virtually ignored in behavior
      analysis until recently. This paper introduces a series of papers from a
      symposium that explored the roles of private events in a science of human
      behavior. We briefly explore the role private events are assigned in several
      behavioral orientations. Next, we discuss several positions on how private events
      might be conceptualized within a behavior-analytic framework. We conclude by
      noting that the dearth of research and conceptualizations about private events
      unnecessarily limits the theoretical or conceptual understanding on which applied
      behavior analysts base their work. With this paper and the papers that follow, we
      hope to spark research, discussion, and yes, thinking, about the roles of
      thinking and feeling.

PMID- 22478335
TI  - Establishing operations, cognition, and emotion.
AB  - In this paper we argue that behavior analysts have tended to neglect the study of
      important aspects of complex human behavior, including cognition and emotion.
      This relative neglect has been costly in terms of mainstream psychology's
      perception of the field of behavior analysis and in terms of our ability to
      provide a more thorough account of human behavior. Observations and findings from
      the clinical context are offered as examples of behavior that are not readily
      explained by the three-term contingency, and we argue that an adequate account of
      these behaviors must include principles derived from recent behavior-analytic
      work, in particular a better understanding of the short- and long-term effects of
      establishing operations. The concept of the establishing operation and its
      implications for understanding complex human behavior are discussed.

PMID- 22478336
TI  - Why it is crucial to understand thinking and feeling: An analysis and application
      to drug abuse.
AB  - Behavior analysis has long accepted the legitimacy of the analysis of private
      events in a natural science of behavior. However, the topic has languished as a
      focus of empirical research in either applied or basic arenas. We argue that
      recent empirical work examining the bidirectional nature of verbal relations may
      shed light on the role of private events in complex human behavior. Skinner
      argued that although it would be possible to analyze private events, we need not,
      because thoughts and feelings were viewed as co-occuring products of the same
      contingencies that are responsible for changes in overt responses. However, the
      bidirectional transformation of stimulus function inherent in verbal behavior
      changes the way that private events participate in complex behavioral episodes
      for verbal organisms. We examine why we have reached such a conclusion, with
      special emphasis on the role of self-awareness. Finally, we conclude with an
      application of our analysis to the problem of substance abuse.

PMID- 22478337
TI  - Thinking about thinking and feeling about feeling.
AB  - Traditional clinical psychology generally posits "mental" events that differ from
      "behavioral" events. Mental events are not publicly observable, take place in a
      different dimension from overt behavior, and are the topic of primary concern.
      For example, mental events are often taken to be causes of troublesome overt
      behavior. In addition, the mental events themselves may be regarded as
      troublesome, independent of their relation to any specific overt behavior.
      Therapy is usually aimed at fixing these troublesome mental events, under an
      assumption that improvement in the client's status will follow in due course.
      Behavior analysis has its own position on the relations among clinical matters,
      overt behavior, and such private events as thinking and feeling. In a behavior
      analytic view, private events are behavioral phenomena rather than mental
      phenomena. They are not initiating causes of behavior; rather, they are
      themselves caused by antecedent conditions, but they may contribute to
      discriminative control over subsequent behavior, both verbal and nonverbal.
      Verbal processes are viewed as vitally important in understanding troublesome
      behavior. However, the circumstances that cause both the troublesome private
      events and the troublesome behavior in the first place still need to be
      addressed. Finally, clinical behavior analysis will need to market its insights
      into diagnosis and treatment very adroitly, because it rejects the mentalism upon
      which most traditional forms of therapy are predicated and the mentalism that
      most consumers expect to encounter.

PMID- 22478338
TI  - Development and function of consequence classes in operant behavior.
AB  - The term class has been discussed extensively in the behavioral literature for
      groups of stimuli or responses that share a common function. In contrast, the
      concept of consequence class, including its definition, its formation, and other
      relevant characteristics, has not been the topic of much attention in the
      literature. Issues pertaining to consequence classes are discussed to provide a
      more thorough analysis of the units of operant and discriminated operant
      functional relations. The concept of class for consequences provides a means to
      integrate data and theory from the behavior-analytic literature.

PMID- 22478339
TI  - Relational frame theory and Skinner's Verbal Behavior: A possible synthesis.
AB  - The current article suggests a possible synthesis of Skinner's (1957) treatment
      of verbal behavior with the more recent behavioral interpretation of language
      known as relational frame theory. The rationale for attempting to combine these
      two approaches is first outlined. Subsequently, each of the verbal operants
      described by Skinner is examined and subjected to a relational frame analysis. In
      each case, two types of operants are identified; one based on direct
      contingencies of reinforcement and the other based on arbitrarily applicable
      relational responding. The latter operants are labeled verbal because they can be
      distinguished from other forms of social behavior, and they appear to possess the
      symbolic or referential qualities often ascribed to human language. By applying
      relational frame theory to Skinner's verbal operants, we aim to contribute
      towards the development of a modern behavior-analytic research agenda in human
      language and cognition.

PMID- 22478340
TI  - Positive behavior support: Expanding the application of applied behavior
      analysis.
AB  - Positive behavior support (PBS) is an approach to providing services to
      individuals who exhibit challenging behavior. Since its inception in the early
      1990s, PBS has received increasing attention from the behavior-analytic
      community. Some behavior analysts have embraced this approach, but others have
      voiced questions and concerns. In this paper we describe the framework of PBS and
      show that it is consistent with the tenets of behavior analysis. Also, we
      illustrate how the framework of PBS might be used to guide practitioners and
      researchers in the field of applied behavior analysis. We hope to demonstrate
      that PBS offers useful suggestions regarding how applied behavior analysts can
      design and evaluate effective programs for people with developmental disabilities
      or behavioral challenges.

PMID- 22478341
TI  - Quantitative summaries of single-subject studies: What do group comparisons tell
      us about individual performances?
AB  - Kollins, Newland, and Critchfield (1999) responded to our comments about their
      review by arguing that their quantitative summary was not a meta-analysis and
      should not be criticized in these terms. We reply that regardless of what they
      call their review, it included confounding effects that make interpretations of
      the results problematic. Kollins et al. also argued that unexpected findings of
      the sort they reported can serve as a spur for further research. We reply that
      the understanding of findings that deviate from existing knowledge may well
      require empirical investigation. Such endeavors, however, should begin with an
      evaluation of the review procedures that suggested the existence of the
      differences. Finally, we emphasize that quantitative summaries of individual data
      are, in the end, a form of group comparison. The implications of using group
      methods to clarify individual data deserve frank recognition in discussions of
      the outcomes.

PMID- 22478342
TI  - The good, the bad, and the aggregate.
AB  - To evaluate progress and focus goals, scientific disciplines need to identify
      relations that are robust across many situations. One approach is the literature
      review, which characterizes generality across studies. Some writers (e.g., Baron
      & Derenne, 2000) claim that quantitative literature reviews, but not narrative
      reviews, violate the methodological precepts of behavior analysis by pooling data
      from nonidentical studies. We argue that it is impossible to assess generality
      without varying the context in which relationships are studied. Properly chosen
      data-aggregation strategies can reveal which behavior-environment relations are
      general and which are procedure dependent. Within behavior analysis, reluctance
      to conduct quantitative reviews may reflect unsupported assumptions about the
      consequences of aggregating data across studies. Whether specific data
      aggregation techniques help or harm a research program is an empirical issue that
      cannot be resolved by unstructured discussion. Some examples of how aggregation
      has been used in identifying behavior-environment relations are examined.

PMID- 22478343
TI  - Behavior analysis and the R&D paradigm.
AB  - This paper considers research and development (R&D) as a style of investigation
      that holds promise for the field of behavior analysis. Contrasted with academic
      style research, R&D tends to be highly targeted toward achievement of specific
      outcomes, which are determined by a user community. R&D is typically
      multidisciplinary in character and is coordinated by a funding source. R&D
      usually includes extensive field testing and systematically addresses technology
      transfer. A program of R&D focused on detector dogs serves as an exemplar of this
      approach for behavior analysis.

PMID- 22478344
TI  - Early intensive behavioral intervention: emergence of a consumer-driven service
      model.
AB  - Parents are becoming influential stimulators and shapers of public policy in
      regard to educational services for their children. Increasingly, this advocacy
      has created a controversy about the role of applied behavior analysis as a
      foundation for early intensive behavioral intervention in autism. Uncertainties
      exist in policy regarding the role of behavior analysis in early intervention and
      the capacity of behavior analysis to field a trained work force. Based on
      contacts with parents of children with autism and information available in a
      variety of forms on the Internet, there is a rising demand for fundamentally
      better early intervention services that are available and accessible, provide
      active intervention, and are based on principles of behavior analysis.
      Contemporary movements in special and early education, however, appear to be
      nonconducive to scientifically based treatments, and school districts seem
      hostile to an increasing role for behavior analysis and to the establishment of
      services that are responsive to changing parental priorities for the education of
      their children with autism and related disorders.

PMID- 22478345
TI  - Varieties of scientific explanation.
AB  - Scientific explanations often take one of two forms. The first is instantiation.
      According to this form, an event is said to be explained when it can be expressed
      as some particular value of a variable in a general proposition, equation, or
      law. One example of instantiation in psychology is Stevens' psychophysical law.
      Another is the matching law in the experimental analysis of behavior. A second
      form of explanation is a deduction from a covering law. According to this form,
      an event is said to be explained when its description follows as a valid logical
      deduction in an argument that has a covering law as one premise and a statement
      of antecedent conditions as another premise. Examples of covering law
      explanations in psychology are found in traditional neobehaviorism, which sought
      to develop laws of behavior so that observed behavioral events could be explained
      as deductions therefrom. Strictly speaking, neither form of explanation is
      consistent with behavior-analytic explanations derived from Skinner's radical
      behaviorism, which emphasize the pragmatic sources and contributions of the
      verbal behavior regarded as explanatory.

PMID- 22478346
TI  - Behavioral pragmatism: no place for reality and truth.
AB  - The current article begins by reviewing L. J. Hayes's claim that pragmatism
      relies on a correspondence-based truth criterion. To evaluate her claim, the
      concept of the observation sentence, proposed by the pragmatist philosopher W. V.
      Quine, is examined. The observation sentence appears to remove the issue of
      correspondence from Quine's pragmatist philosophy. Nevertheless, the issue of
      correspondence reemerges, as the problem of homology, when Quine appeals to
      agreement between or among observation sentences as the basis for truth. Quine
      also argues, however, that the problem of homology (i.e., correspondence) should
      be ignored on pragmatic grounds. Because the problem is simply ignored, but not
      resolved, there appears to be some substance to Hayes's claim that pragmatism
      relies ultimately on correspondence as a truth criterion. Behavioral pragmatism
      is then introduced to circumvent both Hayes's claim and Quine's implicit appeal
      to correspondence. Behavioral pragmatism avoids correspondence by appealing to
      the personal goals (i.e., the behavior) of the scientist or philosopher as the
      basis for establishing truth. One consequence of this approach, however, is that
      science and philosophy are robbed of any final or absolute objectives and thus
      may not be a satisfactory solution to philosophers. On balance, behavioral
      pragmatism avoids any appeal to correspondence-based truth, and thus it cannot be
      criticized for generating the same philosophical problems that have come to be
      associated with this truth criterion.

PMID- 22478347
TI  - Escalation research: providing new frontiers for applying behavior analysis to
      organizational behavior.
AB  - Decision fiascoes such as escalation of commitment, the tendency of decision
      makers to "throw good money after bad," can have serious consequences for
      organizations and are therefore of great interest in applied research. This paper
      discusses the use of behavior analysis in organizational behavior research on
      escalation. Among the most significant aspects of behavior-analytic research on
      escalation is that it has indicated that both the patterns of outcomes that
      decision makers have experienced for past decisions and the patterns of responses
      that they make are critical for understanding escalation. This research has also
      stimulated the refinement of methods by researchers to better assess decision
      making and the role reinforcement plays in it. Finally, behavior-analytic
      escalation research has not only indicated the utility of reinforcement
      principles for predicting more complex human behavior but has also suggested some
      additional areas for future exploration of decision making using behavior
      analysis.

PMID- 22478348
TI  - Collegiate contingencies.
AB  - We discuss contemporary trends and developments that affect colleges and
      universities and describe several central contingencies that have given rise to,
      maintain, and operate in response to these trends and developments. We identify
      the differential impacts of these contingencies on faculty, students, and
      administrators in various types of higher education institutions. These
      contingencies are sources of conflict between and among these three groups within
      the academy that, we argue, cause significant instability in contemporary
      academe. We discuss prominent domains of this dis-equilibrium and propose several
      general interventions to address the sources of the instability.

PMID- 22478349
TI  - Understanding complex behavior: the transformation of stimulus functions.
AB  - The transformation of stimulus functions is said to occur when the functions of
      one stimulus alter or transform the functions of another stimulus in accordance
      with the derived relation between the two, without additional training. This
      effect has been demonstrated with a number of derived stimulus relations,
      behavioral functions, experimental preparations, and subject populations. The
      present paper reviews much of the existing research on the transformation of
      stimulus functions and outlines a number of important methodological and
      conceptual issues that warrant further attention. We conclude by advocating the
      adoption of the generic terminology of relational frame theory to describe both
      the derived transformation of stimulus functions and relational responding more
      generally.

PMID- 22478351
TI  - Women in applied behavior analysis.
AB  - The status of women in applied behavior analysis was examined by comparing the
      participation of women in the Journal of Applied Behavior Analysis (JABA) to
      their participation in three similar journals. For all journals, the percentage
      of articles with at least one female author, the percentage of authors who are
      female, and the percentage of articles with a female first author increased from
      1978 to 1997. Participation by women in JABA was equal to or greater than
      participation by women in the comparison journals. However, women appeared as
      authors on papers in special sections of Behavior Modification substantially more
      often when the editor was female than when the editor was male. In addition,
      female membership on the editorial boards of JABA, Behavior Modification, and
      Behaviour Research and Therapy failed to increase from 1978 to 1997. We conclude
      that a "glass ceiling" reduces the participation of women at the highest levels
      of applied behavior analysis and related fields.

PMID- 22478350
TI  - Sources cited most frequently in the experimental analysis of human behavior.
AB  - We conducted an analysis of the sources cited most frequently in primary
      empirical reports in the experimental analysis of human behavior (EAHB) published
      in four journals between 1990 and 1999. Citation patterns suggest that modern
      EAHB is topically focused and relatively independent of both animal operant
      research and human research conducted outside of behavior analysis.

PMID- 22478352
TI  - Reflections on the glass ceiling: women in the experimental analysis of behavior.
AB  - McSweeney and Swindell (1998) sought to determine whether men and women are
      treated equitably in the experimental analysis of behavior. They purported to
      show that women participate less in the Journal of the Experimental Analysis of
      Behavior than in similar journals and that the participation of women decreases
      with increases in selectivity. Their data were difficult to interpret, however,
      because they did not present the variability in the mean data drawn from
      different individuals over time. My analyses were not in accord with their
      conclusions. When the percentage of associate editors who are women was
      considered along with the mean percentages McSweeney and Swindell reported for
      other measures, participation did not systematically decrease with increases in
      selectivity in recent years. As quantified in terms of their number of
      publications in the Journal of the Experimental Analysis of Behavior, women who
      were editorial board members and associate editors were not more highly selected
      than their male counterparts. Finally, in the recent period from 1996 to 1998,
      although women submitted fewer manuscripts to the journal, rejection ratios did
      not differ for men and women. Efforts to increase the participation of women in
      the experimental analysis of behavior may best be directed toward recruitment and
      retention rather than some of the suggestions proposed by McSweeney and Swindell
      (1998), which could inadvertently create different standards for women's work.

PMID- 22478354
TI  - Certification, accreditation, and quality control in behavior analysis.
AB  - Implementing quality control measures in the discipline and professional practice
      of behavior analysis is a challenging, but nevertheless important, step in the
      evolution of our field. The Association for Behavior Analysis currently seeks to
      ensure quality in behavior analysis by sponsoring an accreditation program for
      graduate academic programs and by promoting certification of individual
      practitioners. The accreditation reviews are conducted by ABA, whereas
      certification status is awarded by an independent, nonprofit credentialing
      entity: the Behavior Analyst Certification Board, Inc. Among the challenges that
      ABA faces as it pursues various quality control measures, particularly in its
      educational programs, are (a) how extensively should academic programs specify
      the verbal and nonverbal terminal repertoires in all three branches of behavior
      analysis (applied, experimental, and conceptual); (b) how extensively should
      programs that emphasize applied behavior analysis integrate science-based
      criteria for the evaluation of interventions; and (c) how extensively should
      programs that emphasize service delivery include training in formal research
      methodology.

PMID- 22478353
TI  - Pervasive negative effects of rewards on intrinsic motivation: The myth
      continues.
AB  - A major concern in psychology and education is that rewards decrease intrinsic
      motivation to perform activities. Over the past 30 years, more than 100
      experimental studies have been conducted on this topic. In 1994, Cameron and
      Pierce conducted a meta-analysis of this literature and concluded that negative
      effects of reward were limited and could be easily prevented in applied settings.
      A more recent meta-analysis of the literature by Deci, Koestner, and Ryan (1999)
      shows pervasive negative effects of reward. The purpose of the present article is
      to resolve differences in previous meta-analytic findings and to provide a meta
      analysis of rewards and intrinsic motivation that permits tests of competing
      theoretical explanations. Our results suggest that in general, rewards are not
      harmful to motivation to perform a task. Rewards given for low-interest tasks
      enhance free-choice intrinsic motivation. On high-interest tasks, verbal rewards
      produce positive effects on free-choice motivation and self-reported task
      interest. Negative effects are found on high-interest tasks when the rewards are
      tangible, expected (offered beforehand), and loosely tied to level of
      performance. When rewards are linked to level of performance, measures of
      intrinsic motivation increase or do not differ from a nonrewarded control group.
      Overall, the pattern of results indicates that reward contingencies do not have
      pervasive negative effects on intrinsic motivation. Theoretical and practical
      implications of the findings are addressed.

PMID- 22478355
TI  - Following rules in the intermontane west: 19th-century mormon settlement.
AB  - The academic discipline of human geography is concerned with human activities,
      especially as these relate to physical landscapes and contribute to the
      modification of those landscapes. Although little attention has been paid to
      objectivist philosophies to inform human geography, behavior analysis might offer
      a useful explanatory model. As an example, a behavior analysis of selected
      aspects of 19th-century Mormon movement and settlement in the intermontane West
      is conducted. Mormons are a society of believers who practice cooperative effort
      and support for other members, and the Mormon church is governed by priesthood
      authority with members being called to perform tasks. This analysis employs the
      concepts of metacontingency, rule-governed behavior, and delayed reinforcement to
      analyze how Mormons settled the intermontane West.

PMID- 22478356
TI  - Intimacy: A behavioral interpretation.
AB  - This paper proposes that intimacy is a process that emerges from a sequence of
      events in which behavior vulnerable to interpersonal punishment is reinforced by
      the response of another person. These intimate events result in an increase in
      the probability of behavior vulnerable to interpersonal punishment in the
      presence of the reinforcing partner. The process results in intimate partnership
      formation and reports of feeling intimate. In addition to positing an operant
      process integrating the various components of intimacy, the theory also posits
      that the punishment of interpersonally vulnerable behavior is an integral aspect
      of intimate partnership formation and that intimate partnerships can develop that
      reinforce behavior that may be destructive both to the individual and to others.

PMID- 22478358
TI  - Editorial.

PMID- 22478357
TI  - The glass ceiling is not fragile: A response to Odum (2000).
AB  - Odum (2000) criticized our recent conclusions about the participation of women in
      the experimental analysis of behavior (McSweeney & Swindell, 1998). We address
      her criticisms here. We argue against the need for statistical tests. We show
      that our conclusions still apply to all journals except the Journal of the
      Experimental Analysis of Behavior even when we include the senior editorial staff
      along with members of the editorial board. We argue that the data that Odum
      provides to show gender equity are limited, inconsistent with past findings, and
      hard to interpret in the absence of other data. Finally, we argue that Odum
      failed to address our most convincing argument for gender inequity and
      misinterpreted our suggestions for improvements.

PMID- 22478359
TI  - Some reflections on 25 years of the association for behavior analysis: Past,
      present, and future.
AB  - This paper offers some reflections on the discipline and profession of behavior
      analysis, as well as on the Association for Behavior Analysis (ABA), on the
      occasion of the association's 25th anniversary. It is based on a panel session
      conducted at the 1999 convention that included six past presidents of ABA (Donald
      M. Baer, Judith E. Favell, Sigrid S. Glenn, Philip N. Hineline, Jack Michael, and
      Edward K. Morris) and its current Executive Director and Secretary-Treasurer
      (Maria E. Malott). Among the topics addressed were (a) the survival of behavior
      analysis in university and cultural contexts, (b) the training of behavior
      analytic researchers and practitioners, (c) relations between basic and applied
      research, (d) convergences between behavior analysis and other disciplines, (e)
      the structure and function of ABA, and (f) the importance of students for the
      future of the association, the discipline, and the profession. Questions from the
      audience raised issues concerning the relevance of major behavior-analytic
      journals, advances in behavior analysis since the death of B. F. Skinner, and the
      availability of accessible, popular material on applied behavior analysis.

PMID- 22478360
TI  - The human side of animal behavior.
AB  - An important element of behavioral research with nonhuman animals is that
      insights are drawn from it about human behavior, what is called here the human
      side of animal behavior. This article examines the origins of comparing human
      behavior to that of other animals, the ways in which such comparisons are
      described, and considerations that arise in evaluating the validity of those
      comparisons. The rationale for such an approach originated in the reductionism of
      experimental physiology and the understanding of the commonalities of all life
      forms promulgated by Darwinian evolutionary biology. Added more recently were
      such observations as the relative simplicity of animal behavior, tempered by the
      constraints placed on resulting comparisons by the absence of verbal behavior in
      animals. The construction of comparisons of human behavior to that of animals may
      be framed on the basis of Skinner's (1957) distinction between the metaphorical
      and generic forms of the extended tact. Both ordinary and systematic comparisons
      of animal and human behavior are congruent with Skinner's extended tact
      framework. The most general consideration in evaluating comparisons of animal and
      human behavior is that a functional basis for the claimed similarity be
      established. Systematic analysis and convergent evidence also may contribute to
      acceptability of these comparisons. In the final analysis, however, conclusions
      about the human side of animal behavior are nondeductively derived and often are
      assessed based on their heuristic and pragmatic value. Such conclusions represent
      a valuable contribution to understanding the human animal and in developing
      practical solutions to problems of human behavior to which much of psychology is
      dedicated.

PMID- 22478361
TI  - A step towards ending the isolation of behavior analysis: A common language with
      evolutionary science.
AB  - In spite of repeated efforts to explain itself to a wider audience, behavior
      analysis remains a largely misunderstood and isolated discipline. In this article
      we argue that this situation is in part due to the terms we use in our technical
      discussions. In particular, reinforcement and punishment, with their vernacular
      associations of reward and retribution, are a source of much misunderstanding.
      Although contemporary thinking within behavior analysis holds that reinforcement
      and punishment are Darwinian processes whereby behavioral variants are selected
      and deselected by their consequences, the continued use of the terms
      reinforcement and punishment to account for behavioral evolution obscures this
      fact. To clarify and simplify matters, we propose replacing the terms
      reinforcement and punishment with selection and deselection, respectively. These
      changes would provide a terminological meeting point with other selectionist
      sciences, thereby increasing the likelihood that behavior analysis will
      contribute to Darwinian science.

PMID- 22478362
TI  - The premack principle, response deprivation, and establishing operations.
AB  - This paper describes response deprivation as an establishing operation. In this
      context, we review the concept of establishing operation, in particular, its
      reinforcer-establishing and evocative effects; we place response deprivation in
      the literature on the reinforcing effects of behavioral activity, wherein
      response deprivation subsumes the Premack principle; we describe the reinforcer
      altering and evocative effects of response deprivation; and we address a
      methodological concern about the evocative effect. In closing, we discuss some
      conceptual and empirical implications of the foregoing analyses.

PMID- 22478363
TI  - Delayed rule following.
AB  - Although the elements of a fully stated rule (discriminative stimulus [S(D)],
      some behavior, and a consequence) can occur nearly contemporaneously with the
      statement of the rule, there is often a delay between the rule statement and the
      S(D). The effects of this delay on rule following have not been studied in
      behavior analysis, but they have been investigated in rule-like settings in the
      areas of prospective memory (remembering to do something in the future) and goal
      pursuit. Discriminative events for some behavior can be event based (a specific
      setting stimulus) or time based. The latter are more demanding with respect to
      intention following and show age-related deficits. Studies suggest that the
      specificity with which the components of a rule (termed intention) are stated has
      a substantial effect on intention following, with more detailed specifications
      increasing following. Reminders of an intention, too, are most effective when
      they refer specifically to both the behavior and its occasion. Covert review and
      written notes are two effective strategies for remembering everyday intentions,
      but people who use notes appear not to be able to switch quickly to covert
      review. By focusing on aspects of the setting and rule structure, research on
      prospective memory and goal pursuit expands the agenda for a more complete
      explanation of rule effects.

PMID- 22478364
TI  - Understanding metaphor: A relational frame perspective.
AB  - The current article presents a basic functional-analytic interpretation of
      metaphor. This work involves an extension of Skinner's (1957) interpretation of
      metaphor using relational frame theory (RFT). A basic RFT interpretation of a
      particular metaphor is outlined, according to which the metaphor acquires its
      psychological effects when formal stimulus dimensions are contacted via the
      derivation of arbitrary stimulus relations. This interpretation sees the metaphor
      as involving four elements: (a) establishing two separate equivalence relations,
      (b) deriving an equivalence relation between these relations, (c) discriminating
      a formal relation via this equivalence-equivalence relation, and (d) a
      transformation of functions on the basis of the formal relation discriminated in
      the third element. In the second half of the paper, a number of important issues
      with regard to the RFT interpretation of metaphor are addressed.

PMID- 22478365
TI  - Sources for Skinner's pragmatic selectionism in 1945.
AB  - Skinner's pragmatic selectionism shows up strongly in his 1945 publication, "The
      Operational Analysis of Psychological Terms," in which he introduced a
      probabilistic three-term contingency for verbal behavior. This probabilism was
      accompanied by an expanded contextualism and an increased emphasis on
      consequences with a clear alignment to pragmatism. In total, these changes
      represent Skinner's most striking shift from mechanistic and necessitarian values
      to pragmatic selectionism, and these changes may be indebted more to the
      conceptual contributions of others than Skinner acknowledged. Before 1945,
      Skinner made at least some positive associations with the views of Watson,
      Russell, and Carnap. From 1945 and afterwards, he strongly disassociated his
      views on verbal behavior from theirs. Before 1945, Skinner did not associate his
      views with those of Darwin or Peirce. After 1945, he strongly associated his
      views with those of Darwin and Peirce (in one published interview). No sources
      for his pragmatic selectionism, however, were referred to in 1945.

PMID- 22478366
TI  - Acceptance in behavior therapy: Understanding the process of change.
AB  - Acceptance is integral to several cutting-edge behavior therapies. However,
      several questions about acceptance remain to be clearly answered. First, what
      does acceptance look like, and can it be observed and measured? Second, what are
      the behavioral principles involved in the promotion of acceptance? Third, when is
      acceptance indicated or contraindicated as a therapeutic goal? The current paper
      attempts to clarify answers to these questions. The goal is to provide a
      conceptualization of the what, how, and when of acceptance that is accessible to
      behavior analysts, both to promote our understanding of acceptance as a
      behavioral phenomenon and to facilitate its empirical study and therapeutic
      utility.

PMID- 22478367
TI  - Some recurrent issues in the history of behavioral sciences.
AB  - Many issues seem to have appeared, disappeared, and reappeared in the behavioral
      sciences during the 20th century. Salient examples discussed in the present paper
      are consciousness, including the concept itself and consciousness in nonhuman
      animals; the method of introspection; and cognition, including the interpretation
      of mental imagery and the role of language in thinking. One possible explanation
      of the apparent cycles is consistent with a suggestion by John B. Watson:
      Important issues are found to be intractable and are abandoned, but they recur
      when newer theories and methods emerge.

PMID- 22478368
TI  - Neither dark age nor renaissance: Research and authorship trends in the
      experimental analysis of human behavior (1980-1999).
AB  - The anniversary of several milestones in the experimental analysis of human
      behavior (EAHB) provides a prompt for updating previous surveys of EAHB
      publication trends, which portrayed the field's overall health as good but raised
      questions about its breadth and trajectory. For the years 1980 through 1999, we
      examined trends in annual frequency of data-based EAHB articles published in the
      Journal of the Experimental Analysis of Behavior (JEAB); in the topical emphasis
      of those EAHB articles; in the geographic region of origin of EAHB articles; and
      in the relative contributions of new and veteran authors. Our findings show
      continued productivity in the field, but contradict an earlier report by showing
      little sustained growth in EAHB over roughly the past 15 years. In terms of
      authorship, an increasing proportion of EAHB articles are authored by veteran
      investigators, although the field also benefits from a steady infusion of new
      authors. International participation in EAHB is limited, with most EAHB research
      originating in North America. In terms of content, our findings replicate those
      of previous reports in showing stimulus control and reinforcement and punishment
      to be the field's most commonly addressed research topics, although content
      emphases apparently differ across regions of origin. Overall, the data depict
      EAHB at the close of the 20th century as a multifaceted enterprise, one that is
      neither bankrupt nor at its full potential for contributing to the overall
      analysis of behavior. We close with some observations on the value of this type
      of archival research and some suggestions for improving the archival
      characterization of the field.

PMID- 22478369
TI  - Resurgence.

PMID- 22478370
TI  - The discriminative stimulus for punishment or S(Dp).

PMID- 22478371
TI  - Compatibility of person-centered planning and applied behavior analysis.
AB  - In response to Osborne (1999), the aims and practices of person-centered planning
      (PCP) are compared to the basic principles of applied behavior analysis set forth
      by Baer, Wolf, and Risley (1968, 1987). The principal goal of PCP is social
      integration of people with disabilities; it qualifies as a socially important
      behavior, and its problems have been displayed sufficiently. However, social
      integration is a complex social problem whose solution requires access to system
      contingencies that influence lifestyles. Nearly all of the component goals of PCP
      proposed by O'Brien (1987b) have been reliably quantified, although concurrent
      measurement of outcomes such as friendship, autonomy, and respect presents a
      formidable challenge. Behavioral principles such as contingency and contextual
      control are operative within PCP, but problems in achieving reliable
      implementation appear to impede an experimental analysis.

PMID- 22478372
TI  - Editorial.

PMID- 22478373
TI  - Notes from the beginning of time.
AB  - Some remembrances of things past, and their possible relevance to things now.
      These remembrances include notes about informality, research as a social process,
      student training and evaluation, research grants, thesis and dissertation
      proposals, and interdisciplinary collaboration.

PMID- 22478374
TI  - Pioneer profiles: A few minutes with Sid Bijou.
AB  - This article is an interview with Sidney W. Bijou. His education, work,
      accomplishments, and honors in the field of behavior analysis are reviewed and
      described in his own words. Some of his accomplishments include applying operant
      methodology to normal children and children with retardation, extending operant
      methodology with children from the laboratory to the natural environment,
      carrying the banner of behavior analysis to many foreign countries, teaching and
      advising many students of behavior analysis who have become well known as
      behavior analysts, and researching, developing, and commercializing such well
      known products as the Edmark reading program, the Portage parent training
      program, and the Wide Range Achievement Test.

PMID- 22478375
TI  - Essential readings for graduate students in behavior analysis: A survey of the
      JEAB and JABA boards of editors.
AB  - We surveyed the editorial boards of the Journal of the Experimental Analysis of
      Behavior and the Journal of Applied Behavior Analysis in an attempt to construct
      an essential reading list for graduate students in behavior analysis. Respondents
      were asked to list up to 10 behavior-analytic journal articles, 10 behavior
      analytic books, and 5 non-behavior-analytic books or journal articles that they
      felt were essential readings. Several behavior-analytic books were listed by
      members of both editorial boards, suggesting that an understanding of the
      philosophy of radical behaviorism and its basic principles are essential for
      graduate students. In contrast, a number of disparities point to differences in
      training and a lack of integration that may exist between basic and applied
      researchers. However, these disparities might also be indicative of the strength
      of behavior analysis. Finally, several non-behavior-analytic readings draw
      attention to the convergence of behavior analysis and other fields of study.

PMID- 22478376
TI  - Participation by women in developmental, social, cognitive, and general
      psychology: A context for interpreting trends in behavior analysis.
AB  - We examined participation by women in journals devoted to social, developmental,
      cognitive, and general psychology. Authorship and first authorship by women
      increased from 1978 to 1997 for most journals. Participation by women on the
      editorial staff did not keep pace with their increased authorship for social and
      developmental psychology. Based on these trends, women's participation decreased
      with increases in the selectivity of the position for social and developmental
      psychology (a glass ceiling). The development of a glass ceiling suggests that
      the contributions of men and women are not always treated equally (gender
      inequity). Because a similar glass ceiling was reported for journals in behavior
      analysis (McSweeney, Donahoe, & Swindell, 2000; McSweeney & Swindell, 1998), the
      causes of this inequity appear to be relatively widespread. The failure to find a
      glass ceiling for general and cognitive psychology suggests that the inequity
      might be reduced by subtle pressure for diversity in editorial positions and by
      adopting actions that encourage women to pursue research positions.

PMID- 22478377
TI  - Selected publication trends in JEAB: Implications for the vitality of the
      experimental analysis of behavior.
AB  - To provide some insight into the current vitality of the experimental analysis of
      behavior, we updated and extended an analysis by R. A. Williams and Buskist
      (1983) of selected trends in the Journal of the Experimental Analysis of
      Behavior. Specifically, the number of articles published and the percentage of
      those articles that were empirical, the number of different affiliations of
      authors and number of articles per affiliation, the types of subjects used in
      empirical articles, and the topics investigated were analyzed for the years 1958
      through 1999. Although several trends may point to a decline in the overall well
      being of the experimental analysis of behavior, they may also be interpreted as
      signs of progress for the field.

PMID- 22478378
TI  - A review of correspondence training: Suggestions for a revival.
AB  - Doing what is promised or accurately reporting what has been done increases with
      correspondence training. Early research showed that training produced positive
      correlations between saying and doing, but did not always produce useful
      generalized correspondence to new, untrained say-do sequences (Baer, 1990).
      Recent research (reviewed here in detail) questioned early procedures and
      introduced new issues: functional criteria, functional verbal responses, baseline
      measures, and response chains in correspondence training. Correspondence research
      was almost abandoned after 1992. This review suggests new procedures and
      directions to revive this important research area. Specific suggestions are to
      combine correspondence procedures with similar features from ongoing research in
      compliance and self-instruction; consider important guidelines for future
      research derived from recent studies; consider interactions between applied and
      basic research with correspondence issues; compare correspondence between
      different participant cohorts; examine the use of descriptive and functional
      terms; examine punishment procedures; and provide a behavioral analysis of the
      relations between verbal and nonverbal behaviors related to correspondence.

PMID- 22478379
TI  - Relational frame theory: A new paradigm for the analysis of social behavior.
AB  - Recent developments in the analysis of derived relational responding, under the
      rubric of relational frame theory, have brought several complex language and
      cognitive phenomena within the empirical reach of the experimental analysis of
      behavior. The current paper provides an outline of relational frame theory as a
      new approach to the analysis of language, cognition, and complex behavior more
      generally. Relational frame theory, it is argued, also provides a suitable
      paradigm for the analysis of a wide variety of social behavior that is mediated
      by language. Recent empirical evidence and theoretical interpretations are
      provided in support of the relational frame approach to social behavior.

PMID- 22478381
TI  - Up close: Impersonal.

PMID- 22478380
TI  - On the distinction between science and practice: A reply to Thyer and Adkins.

PMID- 22478382
TI  - Pioneer profiles: An interview with Don Baer.
AB  - This is an interview with Donald M. Baer. The interview includes discussion of
      his education at the University of Chicago, his work at the University of
      Washington and the University of Kansas, events that influenced his career, and
      his perspectives on various issues. His accomplishments include developing the
      standards for the practice of applied behavior analysis, creating an empirical
      research base for language training for people with severe disabilities,
      initiating procedures that led to generalized imitation, formulating experimental
      designs for applied behavioral research, and devising procedures for
      generalization and maintenance of behavior.

PMID- 22478383
TI  - Behavior analysis and the study of human aging.
AB  - As the population of older adults continues to rise, psychologists along with
      other behavioral and social scientists have shown increasing interest in this age
      group. Although behavior analysts have contributed to research on aging, the
      focus has been on applications that remedy age-related deficits, rather than a
      concern with aging as a developmental process. In particular, there has been
      little interest in the central theoretical questions that have guided
      gerontologists. How does behavior change with advancing years, and what are the
      sources of those changes? We consider the possibility that this neglect reflects
      the long-standing commitment of behavior analysts to variables that can be
      experimentally manipulated, a requirement that excludes the key variable-age
      itself. We review the options available to researchers and present strategies
      that minimize deviations from the traditional features of behavior-analytic
      designs. Our comments are predicated on the view that aging issues within
      contemporary society are far too important for behavior analysts to ignore.

PMID- 22478384
TI  - Cognitive neuroscience from a behavioral perspective: A critique of chasing
      ghosts with geiger counters.
AB  - Cognitive neuroscience is a growing new discipline concerned with relating
      complex behavior to neuroanatomy. Relatively new advances in the imaging of brain
      function, such as positron emission tomography (PET), have generated hundreds of
      studies that have demonstrated a number of interesting but also potentially
      problematic brain-behavior relations. For example, cognitive neuroscientists
      largely favor interpretations of their data that rely on unobserved hypothetical
      mechanisms. Their reports often contain phraseology such as central executive,
      willed action, and mental imagery. As B. F. Skinner argued for decades, cognitive
      constructs of neurological data may yield nothing more than a conceptual nervous
      system.

PMID- 22478385
TI  - Novelty, stimulus control, and operant variability.
AB  - Although behavior analysis has been criticized for failure to account for
      response novelty, many common behavior-analytic concepts and processes (e.g.,
      selectionism, the operant, reinforcement, and stimulus control) assume
      variability both in the environment and in behavior. The importance of the
      relation between variability and novelty, particularly for verbal behavior, is
      discussed, and concepts used to account for novel behavior are examined.
      Experimental findings also are reviewed that suggest that variability in behavior
      can come under discriminative control, and these findings are applied to describe
      novel instances of behavior that may arise during problem solving. We conclude
      that variations provided and selected by the terms of the three-term contingency
      are powerful means for understanding novel behavior.

PMID- 22478386
TI  - Countercontrol in behavior analysis.
AB  - Countercontrol is a functional class of behavior that is part of Skinner's
      analysis of social behavior. Countercontrol refers to behavioral episodes
      comprised of socially mediated aversive controlling conditions and escape or
      avoidance responses that do not reinforce, and perhaps even punish, controllers'
      responses. This paper suggests that neglect of countercontrol in modern behavior
      analysis is unfortunate because the concept applies to interpersonal and social
      relations the fundamental operant principle that human behavior is both
      controlled and controlling-humans are not passive and inflexible. Countercontrol
      is addressed here in terms of conceptual status, contemporary developments in
      behavior analysis, its importance in a behavior-analytic approach to freedom and
      cultural design, applications, and research. The main conclusion is that
      Skinner's formulation of counter-control is scientifically supported and worthy
      of increased prominence in behavior analysis.

PMID- 22478387
TI  - Some more similarities between Peirce and Skinner.
AB  - C. S. Peirce is noted for pioneering a variety of views, and the case is made
      here for the similarities and parallels between his views and B. F. Skinner's
      radical behaviorism. In addition to parallels previously noted, these
      similarities include an advancement of experimental science, a behavioral
      psychology, a shift from nominalism to realism, an opposition to positivism, a
      selectionist account for strengthening behavior, the importance of a community of
      selves, a recursive approach to method, and the probabilistic nature of truth.
      Questions are raised as to the extent to which Skinner's radical behaviorism, as
      distinguished from his S-R positivism, may be seen as an extension of Peirce's
      pragmatism.

PMID- 22478388
TI  - Interteaching: A strategy for enhancing the user-friendliness of behavioral
      arrangements in the college classroom.
AB  - "Interteaching" is an arrangement for college classroom instruction that departs
      from the standard lecture format and offers an answer to criticisms commonly
      directed at behavioral teaching techniques. This approach evolved from
      exploratory use of small-group arrangements and Ferster and Perrott's (1968)
      "interview technique," leading ultimately to a format that is organized around
      focused dyadic discussion. Specific suggestions are offered that might enable
      both seasoned and novice instructors to incorporate this or similar arrangements
      into their classrooms. This approach retains some key characteristics of Keller's
      personalized system of instruction and precision teaching, but offers greater
      flexibility for strategies that are based on behavioral principles.

PMID- 22478389
TI  - On the relation between applied behavior analysis and positive behavioral
      support.
AB  - Anderson and Freeman (2000) recently defined positive behavioral support (PBS) as
      a systematic approach to the delivery of clinical and educational services that
      is rooted in behavior analysis. However, the recent literature contains varied
      definitions of PBS as well as discrepant notions regarding the relation between
      applied behavior analysis and PBS. After summarizing common definitional
      characteristics of PBS from the literature, we conclude that PBS is comprised
      almost exclusively of techniques and values originating in applied behavior
      analysis. We then discuss the relations between applied behavior analysis and PBS
      that have been proposed in the literature. Finally, we discuss possible
      implications of considering PBS a field separate from applied behavior analysis.

PMID- 22478390
TI  - Inner behavior: Empirical investigations of private events.
AB  - The special section on private events in the Spring 2000 issue of The Behavior
      Analyst discussed the exploration of private events. The four articles focused on
      conceptualizations of issues related to private events and on behavior analysts'
      neglect of the area. This response cites 19 data-based articles and two doctoral
      dissertations involving measurement of what precision teachers term inner
      behavior-thoughts, feelings, and urges. Of the estimated 1.2 million standard
      celeration charts, at least 1,600 are inner behavior charts. These extensive data
      indicate that people can and do count and chart their inner behavior. This
      response discusses findings on inner behavior and its frequency, celeration
      (growth), variability, and improvement using antecedent and consequent events.

PMID- 22478391
TI  - Negative effects of positive reinforcement.
AB  - Procedures classified as positive reinforcement are generally regarded as more
      desirable than those classified as aversive-those that involve negative
      reinforcement or punishment. This is a crude test of the desirability of a
      procedure to change or maintain behavior. The problems can be identified on the
      basis of theory, experimental analysis, and consideration of practical cases.
      Theoretically, the distinction between positive and negative reinforcement has
      proven difficult (some would say the distinction is untenable). When the
      distinction is made purely in operational terms, experiments reveal that positive
      reinforcement has aversive functions. On a practical level, positive
      reinforcement can lead to deleterious effects, and it is implicated in a range of
      personal and societal problems. These issues challenge us to identify other
      criteria for judging behavioral procedures.

PMID- 22478392
TI  - The stitching and the unstitching: What can behavior analysis have to say about
      creativity?
AB  - Traditional critics of behaviorism and behavior analysis have emphasized that
      these approaches cannot deal with creative achievements in the arts or sciences,
      or even in ordinary speech. This essay explores several lines of research and
      conceptual issues from different sources in an effort to refute this claim. The
      emphasis is on scientific and mathematical creativity. Some of the topics
      considered include the role of special practice and manipulation, conditions for
      development of automaticity, the interplay of contingency-controlled and rule
      governed behavior, modeling, abstraction, intuition, the blending of response
      units, and emergent behavior. Some limitations of a behavioral account are also
      considered.

PMID- 22478393
TI  - Some verbal behavior about verbal behavior.
AB  - Beginning with behavior analysts' tendency to characterize verbal behavior as
      "mere" verbal behavior, the author reviews his own attempt to employ it to
      influence both his staff and policies of our government. He then describes its
      role in psychopathology, its effect on speakers in healing themselves and on
      engendering creativity. The paper ends by calling to our attention the role of
      verbal behavior in the construction of behavior analysis.

PMID- 22478394
TI  - Bibliographic processes and products, and a bibliography of the published primary
      source works of B. F. Skinner.
AB  - This paper introduces the nature and practice of bibliography (e.g., definition,
      history, and genres); it reviews the extant B. F. Skinner bibliographies (1958 to
      2001); and it describes the methods used in constructing a new, comprehensive,
      and corrected bibliography of Skinner's primary-source published works. The
      bibliography includes 291 items from across 16 categories of publications (e.g.,
      books, articles, chapters, monographs, book reviews, manuals, encyclopedia
      entries, letters to the editor) and lists them in chronological order (1930 to
      1999). A discussion section addresses the bibliography's limitations, how it
      might be enlarged and expanded, its value for qualitative and quantitative
      historical inquiry, and the beginnings of a "Skinner industry."

PMID- 22478395
TI  - Some proposed relations among the domains of behavior analysis.
AB  - The present article examines the nature of and relations among the domains of
      behavior analysis. It first proposes a set of annotated, descriptive criteria to
      aid in distinguishing the experimental analysis of behavior, applied behavior
      analysis, and service delivery. It then argues that the experimental analysis of
      behavior lies at one end of a continuum of behavior-analytic activity, with
      applied behavior analysis in the middle, service delivery at the other end, and
      the theoretical-philosophical-conceptual position known as "radical behaviorism"
      informing the three domains on the continuum. Finally, it argues that clarifying
      the distinctions among the domains of behavior analysis will help the behavior
      analytic community to focus its efforts in training programs and overall support
      of behavior analysis.

PMID- 22478396
TI  - The structure of the cognitive revolution: an examination from the philosophy of
      science.
AB  - The received view is that psychology has undergone several scientific revolutions
      similar to those that occurred in the physical sciences. Of these, this paper
      will consider the cognitive revolution. Because the arguments in favor of the
      existence of a cognitive revolution are cast using the concepts and terms of
      revolutionary science, we will examine the cognitive revolution using accounts of
      revolutionary science advanced by five influential philosophers of science.
      Specifically, we will draw from the philosophical positions of Popper, Kuhn,
      Lakatos, Laudan, and Gross for the purpose of discussion. We conclude that no
      substantive revolution took place according to these accounts. This conclusion is
      based on data gathered from some of the major participants in the "cognitive
      revolution" and on a general scholarly survey of the literature. We argue that
      the so-called cognitive revolution is best characterized as a socio-rhetorical
      phenomenon.

PMID- 22478397
TI  - Some early similarities and later differences between Bertrand Russell and B. F.
      Skinner.
AB  - B. F. Skinner credited Bertrand Russell with converting him to behaviorism and
      with writing one of the books that most influenced him. Particularly in Skinner's
      early work, there are similarities between Skinner and Russell that extend across
      mathematics, determinism, positivism, verbal behavior, future communities,
      evolution, and pragmatism. Later, Skinner's views changed, and he parted company
      with Russell in most of these areas. Perhaps the most dramatic and fundamental
      departure came when Skinner embraced pragmatism, which Russell said he "hated."
      However, there was a time during which Russell wrote favorably of pragmatism as a
      view for science. Although the similarities between Skinner and Russell may have
      resulted from common cultural influences, Russell appears to deserve credit for
      leading Skinner into the stimulus-response behaviorism of two-term necessities;
      he may also deserve some credit for helping to lead him out of it and into the
      selectionist behaviorism of three-term contingencies.

PMID- 22478398
TI  - Toward an operant model of power in organizations.
AB  - The purpose of this paper is to suggest that behavior analysis can help to
      explain social power. In this approach, an individual's potential for influence
      is thought to be partially a function of his or her access to stimuli that can be
      used as consequences. This access can occur either through direct authority or
      indirectly through social networks and exchanges. Social power is also thought to
      be a function of an individual's skill in delivering the stimuli in ways that
      will have the most impact on behavior. A number of predictions about power based
      on an operant approach are offered.

PMID- 22478399
TI  - Experimental.

PMID- 22478400
TI  - Generalized imitation and generalized matching to sample.

PMID- 22478401
TI  - Behavior analysis, mentalism, and the path to social justice.
AB  - Traditional psychology is mentalistic in the sense that it appeals to inner
      causes in the explanation of behavior. Two examples of mentalism in traditional
      psychology are (a) dispositional attributions and (b) conventional treatments of
      intelligence. These examples may be linked to such pernicious social -isms as
      racism and sexism by noting that some individuals justify engaging in
      discriminatory conduct toward others by appealing to some deficient inner quality
      of those being discriminated against. This sort of mentalistic appeal ultimately
      prevents some members of our society from being integrated into society and from
      progressing down the path of social justice. Behavior analysis offers a
      constructional alternative to the mentalistic views of traditional psychology and
      allows our society as a whole to move down the path.

PMID- 22478402
TI  - Stimulus control topography coherence theory: foundations and extensions.
AB  - Stimulus control topography refers to qualitative differences among members of a
      functional stimulus class. Stimulus control topography coherence refers to the
      degree of concordance between the stimulus properties specified as relevant by
      the individual arranging a reinforcement contingency (behavior analyst,
      experimenter, teacher, etc.) and the stimulus properties that come to control the
      behavior of the organism (experimental subject, student, etc.) that experiences
      those contingencies. This paper summarizes the rationale for analyses of
      discrimination learning outcomes in terms of stimulus control topography
      coherence and briefly reviews some of the foundational studies that led to this
      perspective. We also suggest directions for future research, including pursuit of
      conceptual and methodological challenges to a complete stimulus control
      topography coherence analysis of processes involved in discriminated and
      generalized operants.

PMID- 22478403
TI  - Behavior analysis and social constructionism: some points of contact and
      departure.
AB  - Social constructionists occasionally single out behavior analysis as the field of
      psychology that most closely resembles the natural sciences in its commitment to
      empiricism, and accuses it of suffering from many of the limitations to science
      identified by the postmodernist movement (e.g., K. J. Gergen, 1985a; Soyland,
      1994). Indeed, behavior analysis is a natural science in many respects. However,
      it also shares with social constructionism important epistemological features
      such as a rejection of mentalism, a functional-analytic approach to language, the
      use of interpretive methodologies, and a reflexive stance on analysis. The
      current paper outlines briefly the key tenets of the behavior-analytic and social
      constructionist perspectives before examining a number of commonalties between
      these approaches. The paper aims to show that far from being a nemesis to social
      constructionism, behavior analysis may in fact be its close ally.

PMID- 22478404
TI  - Expanding visions: 1950s applications and extensions of Skinner's operant
      psychology.

PMID- 22478405
TI  - Behavior analysis and the growth of behavioral pharmacology.
AB  - Psychologists, particularly those influenced by the work of B. F. Skinner, played
      a major part in the development of behavioral pharmacology in the 1950s and
      1960s. Revolutionary changes in pharmacology and psychiatry, including the
      discovery of powerful therapeutic agents such as chlorpromazine and reserpine,
      had produced a surge of interest in drug research. Pharmaceutical companies began
      hiring psychologists with operant conditioning backgrounds so as to compete
      successfully in the search for new drugs. Psychologists, most of whom were
      skilled in the behavior-analytic approach, started to assume prominent positions
      as authors and editors for the Journal of Pharmacology and Experimental
      Therapeutics as its emphasis on behavior increased. This also proved true with
      the other publications founded to deal with the popularity of behavioral
      pharmacology. Especially important were contributions by B. F. Skinner, Peter B.
      Dews, and Joseph V. Brady.

PMID- 22478406
TI  - Conflicting approaches: operant psychology arrives at a primate laboratory.
AB  - During a brief period, from 1955 to 1957, behavior analysts, primarily Charles
      Ferster, Roger Kelleher, and John Falk, conducted research on chimpanzees at the
      Yerkes Laboratories of Primate Biology in Orange Park, Florida. This was a time
      of conflict between operant conditioners and more traditional experimental
      psychologists at the national level, and there was a similar conflict at the
      local level in Orange Park. The principal overt issues concerned the use of
      deprivation procedures, the apparatus utilized, and the naming of animals,
      although more fundamental differences probably set the occasion for the disputes.
      The conflicts in Orange Park can be seen as a microcosm of the broader conflicts
      that occurred during a period when the operant approach was being extended and
      applied more broadly than before.

PMID- 22478407
TI  - Skinner boxes for psychotics: operant conditioning at Metropolitan State
      Hospital.
AB  - Between 1953 and 1965, Ogden Lindsley and his associates conducted free-operant
      research with psychiatric inpatients and normal volunteers at Metropolitan State
      Hospital in Waltham, Massachusetts. Their project, originally named "Studies in
      Behavior Therapy," was renamed "Harvard Medical School Behavior Research
      Laboratory" in 1955. This name change and its implications were significant. The
      role of the laboratory in the history of the relationship between the
      experimental analysis of behavior and applied behavior analysis is discussed. A
      case is made for viewing Lindsley's early work as foundational for the subfield
      of the experimental analysis of human behavior that formally coalesced in the
      early 1980s. The laboratory's work is also contextualized with reference to the
      psychopharmacological revolution of the 1950s. Finally, a four-stage framework
      for studying the historical and conceptual development of behavior analysis is
      proposed.

PMID- 22478408
TI  - Comments on the 1950s applications and extensions of Skinner's operant
      psychology.
AB  - These comments address Laties', Dewsbury's, and Rutherford's papers on the
      extension and application of Skinner's operant psychology during the 1950s. I
      begin by reflecting on the papers' overall theme-that the success of behavior
      analysis lies in its practical applications-and add some comments on Planck's
      principle. I then turn to the three papers and address such topics as (a) other
      applications and extensions (e.g., the U.S. space program), (b) relations between
      the research and researchers at the Yerkes Laboratories of Primate Biology (e.g.,
      a Yerkes' researcher in Skinner's laboratory), and (c) human schedule performance
      (e.g., continuity and discontinuity with nonhuman behavior). I end with a
      discussion of the fundamental reason for the success of the extensions and
      applications of behavior analysis-the experimental analysis of behavior.

PMID- 22478409
TI  - Is a new version of philosophical pragmatism necessary? A reply to Barnes-Holmes.
AB  - Barnes-Holmes (2000) discussed certain issues regarding philosophy, pragmatism,
      and behavior analysis, and offered a "behavioral pragmatism" based on or derived
      from behavior-analytic perspectives. In a comparison of certain philosophical
      views, Quine's concept of observation sentences was employed for representing
      pragmatism, but this concept is not sufficiently representative of the literature
      of philosophical pragmatism to warrant the broad conclusions drawn by Barnes
      Holmes. Further, although the extensive and diverse literature of philosophical
      pragmatism has been shown by a number of writers to have various themes and
      perspectives in common with Skinner's radical behaviorism, it is unnecessary to
      extract a limited, generic version of pragmatism because (a) the latter cannot
      match the range and depth of the various extant versions and (b) the problems
      raised by Barnes-Holmes in justification for the new version yield readily to the
      current versions in philosophy. A set of philosophical views may provide
      additional verbal support for a given system of science, and the science of
      behavior analysis may eventually contribute to philosophical discourse. The
      latter, however, will not be achieved by proposing new versions of old
      philosophy, but rather by approaching established philosophical issues in new
      ways.

PMID- 22478410
TI  - A reply to Galizio's "The abstracted operant: a review of relational frame
      theory: a post-Skinnerian account of human language and cognition".

PMID- 22478411
TI  - Hypothetical high-level cognitive functions cannot be localized in the brain:
      another argument for a revitalized behaviorism.
AB  - A key epistemological difference between behaviorism and cognitivism concerns
      their respective attitudes toward the analysis of so-called cognitive processes
      into functional modules. Behaviorists generally say it is not possible.
      Cognitivists argue that this is an achievable goal. The question has been
      concretized by recent developments in brain imaging technology. A consideration
      of the matter suggests that technical and conceptual difficulties abound in the
      effort to localize "high-level cognitive functions" in narrowly circumscribed
      regions of the brain. Some of the most serious involve the ambiguous definition
      of the putative mental components that are to be localized and the generally
      unacknowledged nonlinear complexity of both psychological processes and the
      brain. In addition, the imaging techniques themselves are replete with technical
      difficulties that raise additional questions about this particular application,
      even though these wonderful machines can make extraordinary contributions to our
      knowledge of brain anatomy and physiology. The cumulative implication of these
      difficulties is that the cognitive approach to the study of scientific psychology
      has once again set out on a search for a chimera. New approaches to behaviorism
      may be required to set psychology back on the correct track.

PMID- 22478412
TI  - Effects of rate building on fluent performance: a review and commentary.
AB  - The use of rate-building procedures to encourage the production of high response
      rates and to develop fluency has been increasingly justified by research on
      precision teaching and automaticity. Rate-building procedures often ensure both
      speed and accuracy, and claims have been made that such procedures result in
      greater retention, persistence, and generalization of trained skills, as well as
      preference by students. Given the potential importance of these claims for
      behavior analysts and educators alike, this review assesses the validity,
      generality, and implications of research on rate building. The review revealed
      sparse empirical evidence that retention, persistence, and generalization of
      skills result from the use of rate-building procedures when the effects of
      practice and reinforcement rate are controlled. Given the results of this review,
      the implications are discussed in the context of behavior-analytic research
      (e.g., behavioral momentum), and further research is recommended.

PMID- 22478413
TI  - Toward the globalization of behavior analysis.
AB  - Globalization could facilitate the long-term growth of behavior analysis, and
      although progress has been made, much yet needs to be done. Given the scarcity of
      resources, it is suggested that we draw from successes in the development of
      behavior analysis and establish behavioral programs around the world that embrace
      research, education, and practice as a focus of systematic globalization efforts.
      The strategy would require the implementation of cultural contingencies that
      support initiation and long-term program expansion. For program initiation,
      contingencies are needed to place pioneer behavior analysts in university units
      that would be unlikely to start a behavioral program otherwise. The task of these
      pioneers would be to build a critical mass that would multiply behavior-analytic
      repertoires, obtain research funding, conduct publishable research, and establish
      applied settings. For long-term program development, the field should expand
      internationally as it continues building the infrastructure needed to accelerate
      the demand for behavioral programs in higher education, scholarly work in
      behavior analysis, behavior analysts in existing jobs, and behavioral technology
      in the market place.

PMID- 22478414
TI  - A forgotten resource critical to the future of behavior analysis: undergraduate
      psychology majors.
AB  - The demand for board-certified applied behavior analysts is not being met, and
      there is a perception that fewer students are exposed to systematic courses in
      basic and applied behavior analysis than was true a generation ago. This article
      outlines how we have successfully implemented an undergraduate curriculum in
      behavior analysis within a traditional department of psychology. Certification
      credentials offered by the Behavior Analysis Certification Board facilitated the
      approval of this curriculum, and the cultural practice selection contingencies
      that supported the creation of our curriculum in behavior analysis may be similar
      at other comprehensive universities. Advice for developing an undergraduate
      program in behavior analysis within a psychology department is outlined. We also
      summarize strategies we have used to attract talented students to the courses and
      the significant impact these strategies have had on the number of our graduates
      who pursue graduate training in basic and applied behavior analysis. Attracting
      the best and brightest students to behavior analysis is critical to the future of
      the field.

PMID- 22478416
TI  - Stability over time: is behavior analysis a trait psychology?
AB  - Historically, behavior analysis and trait psychology have had little in common;
      however, recent developments in behavior analysis bring it closer to one of the
      core assumptions of the trait approach: the stability of behavior over time and,
      to a lesser extent, environments. The introduction of the concept of behavioral
      momentum and, in particular, the development of molar theories have produced some
      common features and concerns. Behavior-analytic theories of stability provide
      improved explanations of many everyday phenomena and make possible the expansion
      of behavior analysis into areas that have been inadequately addressed.

PMID- 22478417
TI  - An intentional interpretive perspective.
AB  - To the extent that the concept of intention has been addressed within behavior
      analysis, descriptions of intention have been general and have not specifically
      included important distinctions that differentiate a behavior-analytic approach
      from vernacular definitions of intention. A fundamental difference between a
      behavior-analytic approach and most other psychological approaches is that other
      approaches focus on the necessity of intentions to explain behavior, whereas a
      behavior-analytic approach is directed at understanding the interplay between
      behavior and environment. Behavior-analytic interpretations include the relations
      between the observer's behavior and the environment. From a behavior-analytic
      perspective, an analysis of the observer's interpretations of an individual's
      behavior is inherent in the subsequent attribution of intention. The present
      agenda is to provide a behavior-analytic account of attributing intention that
      identifies the establishing conditions for speaking of intention. Also addressed
      is the extent to which we speak of intentions when the observed individual's
      behavior is contingency shaped or under instructional control.

PMID- 22478418
TI  - Determining essential content for applied behavior analyst practitioners.
AB  - This article reports the procedures and findings of a job-analysis study recently
      conducted by the Behavior Analyst Certification Board, Inc. (BACB) and considers
      some implications of the survey data collected during this process. The job
      analysis focused on the applied sector of the field of behavior analysis and
      limited its inquiry into matters of professional competencies and training. The
      results represent a unique sample of demographic information and valuable
      collection of opinions regarding the competencies and training required of
      applied behavior analyst practitioners. Because these opinions have a direct
      effect on certification task standards and content of the BACB credentialing
      examinations, which in turn drive the curricula of undergraduate and graduate
      programs in applied behavior analysis, it is important to consider what these
      views might mean for the continuing evolution of the field of behavior analysis.

PMID- 22478419
TI  - Two suggestions for the verbal behavior(s) of organisms (i.e., authors).

PMID- 22478420
TI  - Up with this I shall not put: 10 reasons why I disagree with Branch and Vollmer
      on behavior used as a count noun.
AB  - Branch and Vollmer (2004) argue that use of the word behavior as a count noun is
      ungrammatical and, worse, mischaracterizes and ultimately degrades the concept of
      the operant. In this paper I argue that use of behavior as a count noun is a
      reflection of its grammatical status as a hybrid of count and mass noun. I show
      that such usage is widespread across colloquial, referential, and scientific
      documents including the writings of major figures in behavior analysis (most
      notably B. F. Skinner), books describing its applications, and its major
      journals. Finally, I argue against the assertion that such usage degrades the
      concept of the operant, at least in any meaningful way, and argue instead that
      employing eccentric definitions for ordinary words and using arcane terms to
      describe everyday human behavior risks diminishing the influence of behavior
      analysis on human affairs.

PMID- 22478421
TI  - Relational frames: where do they come from? A comment on Barnes-Holmes and Hayes
      (2003).

PMID- 22478422
TI  - A reply to Leigland's "Is a new version of philosophical pragmatism necessary? A
      reply to Barnes-Holmes".

PMID- 22478423
TI  - A call to arms.

PMID- 22478424
TI  - Individual behavior, culture, and social change.
AB  - The principle of operant selection is examined as a prototype of cultural
      selection, and the role of the social environment is suggested as the critical
      element in the emergence of cultural phenomena. Operant contingencies are
      compared to cultural selection contingencies, designated as metacontingencies.
      Both of these types of contingency relations result in evolving lineages of
      recurrences that can become increasingly complex in the number and organization
      of their elements. In addition to its role in the recurring interlocking
      behavioral contingencies that constitute cultural organization, operant behavior
      plays another role in cultures. Although the operants of individuals are
      functionally independent of one another, the behavior of each person may
      contribute to a cumulative effect that is relevant to the well-being of many
      people. Similarly, the outcomes of metacontingencies may also contribute to a
      cumulative effect. The relation between independently evolving operant lineages,
      or between independently evolving cultural lineages, and their cumulative effect
      is identified as a macrocontingency. Macrocontingencies do not involve cultural
      level selection per se. Effective cultural engineering requires identifying the
      macrocontingencies that produce less than desirable effects and altering the
      relevant operant contingencies or metacontingencies to produce change in the
      cumulative effects.

PMID- 22478425
TI  - Whether, when, and why Skinner published on biological participation in behavior.
AB  - This paper brings some data to bear on the criticisms, claims, and arguments that
      Skinner (a) denied or dismissed biological participation in behavior, (b)
      addressed it only late in his career or more often later than earlier, or (c)
      addressed it only because of the overwhelming evidence for it or the criticisms
      that he had overlooked it. For this, we coded Skinner's every primary-source
      publication for three content categories (i.e., genetics, physiology, and
      evolution) and for the extent to which he addressed them (i.e., in publication
      titles, substantively, or in passing). Our findings are that Skinner addressed
      biological participation in over a third of his publications throughout his
      career, albeit more often later than earlier. The latter, however, is accounted
      for by an increase in his base rate of publication and in general conditions and
      specific events in his career, psychology, and science. The discussion addresses
      our research methods; the reasons for and refutations of the criticisms, claims,
      and arguments; and their sources.

PMID- 22478427
TI  - Dynamic changes in reinforcer effectiveness: satiation and habituation have
      different implications for theory and practice.
AB  - Reinforcers lose their effectiveness when they are presented repeatedly. Early
      researchers labeled this loss of effectiveness as satiation without conducting an
      experimental analysis. When such an analysis is conducted, habituation provides a
      more precise and empirically accurate label for the changes in reinforcer
      effectiveness. This paper reviews some of the data that suggest that habituation
      occurs to repeatedly presented reinforcers. It also argues that habituation has
      surprisingly different implications than satiation for theory and practice in
      behavior analysis. For example, postulating that habituation occurs to repeatedly
      presented reinforcers suggests ways for maintaining the strength of an existing
      reinforcer and for weakening the strength of a problematic reinforcer that differ
      from those implied by an account in terms of satiation. An habituation account
      may also lead to different ways of conceptualizing the regulation of behavior.
      For example, habituation may be a single-process contributor to the termination
      of behaviors that are usually attributed to satiation (e.g., ingestive behaviors
      such as eating and drinking), fatigue (e.g., energetic behaviors such as
      running), the waning of attention (e.g., cognitive behaviors such as studying),
      and pharmacodynamic factors (e.g., drug taking).

PMID- 22478428
TI  - The analysis of human behavior in context.
AB  - Does the name of the special interest group, "The Experimental Analysis of Human
      Behavior," imply that those who analyze the behavior of human animals must
      organize themselves apart from those who analyze the behavior of nonhuman
      animals? Is the use of nonhumans in experiments really not relevant to the
      analysis of the behavior of humans? If so, then something must have changed. Many
      differences exist, of course, between the behavior of humans and nonhumans
      humans, for example, cannot fly under their own power-but have we really isolated
      differences in principle, differences that require separate organizations for the
      study of each? I will try to indicate why I believe this is a serious concern,
      where the concern comes from, and what, perhaps, might be done to maintain what
      was once a flourishing bidirectional relation between research with humans and
      nonhumans, in both basic and applied research.

PMID- 22478429
TI  - Toward a behavioral analysis of joint attention.
AB  - Joint attention (JA) initiation is defined in cognitive-developmental psychology
      as a child's actions that verify or produce simultaneous attending by that child
      and an adult to some object or event in the environment so that both may
      experience the object or event together. This paper presents a contingency
      analysis of gaze shift in JA initiation. The analysis describes reinforcer
      establishing and evocative effects of antecedent objects or events,
      discriminative and conditioned reinforcing functions of stimuli generated by
      adult behavior, and socially mediated reinforcers that may maintain JA behavior.
      A functional analysis of JA may describe multiple operant classes. The paper
      concludes with a discussion of JA deficits in children with autism spectrum
      disorders and suggestions for research and treatment.

PMID- 22478430
TI  - Exploring the limits and utility of operant conditioning in the treatment of drug
      addiction.
AB  - This article describes a research program to develop an operant treatment for
      cocaine addiction in low-income, treatment-resistant methadone patients. The
      treatment's central feature is an abstinence reinforcement contingency in which
      patients earn monetary reinforcement for providing cocaine-free urine samples.
      Success and failure of this contingency appear to be an orderly function of
      familiar parameters of operant conditioning. Increasing reinforcement magnitude
      and duration can increase effectiveness, and sustaining the contingency can
      prevent relapse. Initial development of a potentially practical application of
      this technology suggests that it may be possible to integrate abstinence
      reinforcement into employment settings using salary for work to reinforce drug
      abstinence. This research illustrates the potential utility and current
      limitations of an operant approach to the treatment of drug addiction. Similar
      research programs are needed to explore the limits of the operant approach and to
      develop practical applications that can be used widely in society for the
      treatment of drug addiction.

PMID- 22478431
TI  - A behavior-analytic conceptualization of the side effects of psychotropic
      medication.
AB  - A range of behavior-much deemed problematic by society-is treated with behavioral
      methods or psychotropic medications. Although the processes associated with
      behavioral interventions have been investigated using conceptual, experimental,
      and applied analyses, less is known about the behavioral processes associated
      with the use of psychotropic medication. Psychotropic drugs produce at least two
      types of effects of behavioral interest: (a) primary effects of drug action on
      target behaviors and (b) side effects that change the target or other behavior.
      Although an empirical literature exists regarding the former effects, little
      attention has been given to the latter topic. In this paper we offer a conceptual
      analysis of the side effects of psychotropic medication. We propose that the side
      effects of various drugs can influence behavior by functioning as motivating
      operations, conditional or discriminative stimuli, or by establishing new
      response-reinforcer relations. This conceptualization may facilitate the
      empirical analysis of how psychotropic drugs change behavior.

PMID- 22478432
TI  - Impulsive choice and workplace safety: a new area of inquiry for research in
      occupational settings.
AB  - A conceptual argument is presented for the relevance of behavior-analytic
      research on impulsive choice to issues of occupational safety and health.
      Impulsive choice is defined in terms of discounting, which is the tendency for
      the value of a commodity to decrease as a function of various parameters (e.g.,
      having to wait or expend energy to receive the commodity). A high degree of
      discounting is often considered an index of impulsivity. We argue that for
      workers, possible negative consequences (e.g., injury or disease) are often
      disregarded, or discounted, in choices about workplace safety because such
      consequences are typically delayed and uncertain. Furthermore, some evidence
      suggests that certain environmental conditions, such as those that lead to stress
      or sleep deprivation, may increase discounting. Increased discounting, by
      extension, leads to a further devaluation of safety practices and their benefits.
      A call is made for research aimed at more clearly delineating the relation
      between impulsive choice and workplace safety.

PMID- 22478433
TI  - Multiply controlled verbal operants: an analysis and extension to the picture
      exchange communication system.
AB  - This paper presents Skinner's (1957) analysis of verbal behavior as a framework
      for understanding language acquisition in children with autism. We describe
      Skinner's analysis of pure and impure verbal operants and illustrate how this
      analysis may be applied to the design of communication training programs. The
      picture exchange communication system (PECS) is a training program influenced by
      Skinner's framework. We describe the training sequence associated with PECS and
      illustrate how this sequence may establish multiply controlled verbal behavior in
      children with autism. We conclude with an examination of how Skinner's framework
      may apply to other communication modalities and training strategies.

PMID- 22478434
TI  - Studies using single-subject designs in sport psychology: 30 years of research.
AB  - A prominent feature of behavior-analytic research has been the use of single
      subject designs. We examined sport psychology journals and behavioral journals
      published during the past 30 years, and located 40 studies using single-subject
      designs to assess interventions for enhancing the performance of athletes and
      coaches. In this paper, we summarize that body of research, discuss its strengths
      and limitations, and identify areas for future research.

PMID- 22478435
TI  - A refocus on response-rate measurement: comment on Doughty, Chase, and O'Shields
      (2004).

PMID- 22478436
TI  - Extrinsic and intrinsic motivation at 30: Unresolved scientific issues.
AB  - The undermining effect of extrinsic reward on intrinsic motivation remains
      unproven. The key unresolved issues are construct invalidity (all four
      definitions are unproved and two are illogical); measurement unreliability (the
      free-choice measure requires unreliable, subjective judgments to infer intrinsic
      motivation); inadequate experimental controls (negative affect and novelty, not
      cognitive evaluation, may explain "undermining" effects); and biased metareviews
      (studies with possible floor effects excluded, but those with possible ceiling
      effects included). Perhaps the greatest error with the undermining theory,
      however, is that it does not adequately recognize the multifaceted nature of
      intrinsic motivation (Reiss, 2004a). Advice to limit the use of applied behavior
      analysis based on "hidden" undermining effects is ideologically inspired and is
      unsupported by credible scientific evidence.

PMID- 22478437
TI  - The aesthetics of behavioral arrangements.
AB  - With their origins in scientific validation, behavior-analytic applications have
      understandably been developed with an engineering rather than a crafting
      orientation. Nevertheless, traditions of craftsmanship can be instructive for
      devising aesthetically pleasing arrangements-arrangements that people will try,
      and having tried, will choose to continue living with. Pye (1968) provides
      suggestions for this, particularly through his distinctions between workmanship
      of risk versus workmanship of certainty, and the mating of functional precision
      with effective or otherwise pleasing variability. Close examination of
      woodworking tools as well as antique machines offers instructive analogues that
      show, for instance, that misplaced precision can be dysfunctional when precision
      is not essential to a design. Variability should be allowed or even encouraged.
      Thus, in the design of behavioral contingencies as well as of practical or purely
      aesthetic objects, "precise versus variable" is not necessarily a distinction
      between good and bad. More generally, behavior analysts would do well to look
      beyond their technical experience for ways to improve the aesthetics of
      contingency design while continuing to understand the resulting innovations in
      relation to behavior-analytic principles.

PMID- 22478438
TI  - Ernst Mach and B. F. Skinner: Their similarities with two traditions for verbal
      behavior.
AB  - Ernst Mach is most closely associated with a positivism that demanded a language
      of close contact with reality. Mach linked this view with the tradition of the
      quest for an ideal language in which meaning is a property of a word. Logical
      positivism and the S-R psychology of the early B. F. Skinner also participated in
      this ideal-language positivism. In addition, Mach showed an affinity with another
      tradition-a pragmatic-selectionist tradition-although that tradition and Mach's
      similarities with it were not as well developed. Mach showed no difficulty in
      jointly maintaining both of these traditions although they have been regarded as
      deeply incompatible. When the later Skinner adopted a pragmatic selectionism for
      his later views on verbal behavior, he rejected his earlier views that were
      aligned with S-R psychology as well as with logical positivism and its
      sympathizers. Nevertheless, some statements consistent with "meaning is a
      property of a word" remained for some time in Skinner's writing.

PMID- 22478439
TI  - Applying behavior analysis to school violence and discipline problems: Schoolwide
      positive behavior support.
AB  - School discipline is a growing concern in the United States. Educators frequently
      are faced with discipline problems ranging from infrequent but extreme problems
      (e.g., shootings) to less severe problems that occur at high frequency (e.g.,
      bullying, insubordination, tardiness, and fighting). Unfortunately, teachers
      report feeling ill prepared to deal effectively with discipline problems in
      schools. Further, research suggests that many commonly used strategies, such as
      suspension, expulsion, and other reactive strategies, are not effective for
      ameliorating discipline problems and may, in fact, make the situation worse. The
      principles and technology of behavior analysis have been demonstrated to be
      extremely effective for decreasing problem behavior and increasing social skills
      exhibited by school children. Recently, these principles and techniques have been
      applied at the level of the entire school, in a movement termed schoolwide
      positive behavior support. In this paper we review the tenets of schoolwide
      positive behavior support, demonstrating the relation between this technology and
      applied behavior analysis.

PMID- 22478440
TI  - "Golden oldies" in a laboratory course in the experimental analysis of behavior.
AB  - A common problem in teaching undergraduate courses in the experimental analysis
      of behavior (EAB) is that the contemporary research literature is largely not
      comprehensible to most undergraduates. A suggested solution is the use of
      research articles from the early days of EAB. These are not only easy to
      understand but provide additional educational benefits. A reading list and an
      organizational structure for an undergraduate laboratory course in EAB are
      suggested.

PMID- 22478441
TI  - The relations among fluency, rate building, and practice: A response to Doughty,
      Chase, and O'Shields (2004).

PMID- 22478442
TI  - A reply to Uttal (2004).

PMID- 22478443
TI  - Positive and negative reinforcement: Should the distinction be preserved?
AB  - Michael (1975) reviewed efforts to classify reinforcing events in terms of
      whether stimuli are added (positive reinforcement) or removed (negative
      reinforcement). He concluded that distinctions in these terms are confusing and
      ambiguous. Of necessity, adding a stimulus requires its previous absence and
      removing a stimulus its previous presence. Moreover, there is no good basis,
      either behavioral or physiological, that indicates the involvement of distinctly
      different processes, and on these grounds he proposed that the distinction be
      abandoned. Despite the cogency of Michael's analysis, the distinction between
      positive and negative reinforcement is still being taught. In this paper, we
      reconsider the issue from the perspective of 30 years. However, we could not find
      new evidence in contemporary research and theory that allows reliable
      classification of an event as a positive rather than a negative reinforcer. We
      conclude by reiterating Michael's admonitions about the conceptual confusion
      created by such a distinction.

PMID- 22478445
TI  - Variables of which values are a function.
AB  - The ordinary-language concept of values has a complex history in psychology and
      in science generally. The traditional fact-value distinction commonly found in
      traditional scientific perspectives has been challenged by the varieties of
      philosophical pragmatism, which have similarities to Skinner's radical
      behaviorism. Skinner's challenge to the fact-value distinction maintained that
      the phenomena of both "facts" and "values" are a matter of contingencies of
      environment-behavior interaction, and both phenomena may be observed when a
      scientist does research or makes recommendations in applied settings based on
      that research. Some of the processes and variables relevant to an analysis of
      values as behavioral phenomena are described, and examples of both nonverbal and
      verbal contingencies are considered, along with implications for the values of an
      individual and a culture. If the various issues of methodology can be addressed
      successfully, then behavior analysis will be in the position to move beyond
      descriptive studies of values, such as those found in humanistic psychology, by
      providing analyses of the variables of which values are a function.

PMID- 22478444
TI  - B. F. Skinner's contributions to applied behavior analysis.
AB  - Our paper reviews and analyzes B. F. Skinner's contributions to applied behavior
      analysis in order to assess his role as the field's originator and founder. We
      found, first, that his contributions fall into five categorizes: the style and
      content of his science, his interpretations of typical and atypical human
      behavior, the implications he drew from his science for application, his
      descriptions of possible applications, and his own applications to nonhuman and
      human behavior. Second, we found that he explicitly or implicitly addressed all
      seven dimensions of applied behavior analysis. These contributions and the
      dimensions notwithstanding, he neither incorporated the field's scientific (e.g.,
      analytic) and social dimensions (e.g., applied) into any program of published
      research such that he was its originator, nor did he systematically integrate,
      advance, and promote the dimensions so to have been its founder. As the founder
      of behavior analysis, however, he was the father of applied behavior analysis.

PMID- 22478446
TI  - Operant psychology goes to the fair: Marian and Keller Breland in the popular
      press, 1947-1966.
AB  - Marian and Keller Breland pioneered the application of operant psychology to
      commercial animal training during the 1940s and 1950s. The Brelands' story is
      relatively unknown in the history of behavior analysis. Using information from
      the Breland-Bailey papers, this paper describes the development and activities of
      Animal Behavior Enterprises (ABE), the Brelands' animal training business. We
      also review popular press coverage of the Brelands between 1947 and 1966 to
      investigate the level of public exposure to ABE-trained animals and to the
      principles and methods of operant psychology. An examination of 308 popular print
      articles featuring the Brelands indicates that there was public exposure of
      behavior analysis through the popular press coverage of ABE-trained animals.
      Furthermore, the expansion of operant methods to the marine mammal and bird
      training industries can be linked to the Brelands' mass media exposure.

PMID- 22478447
TI  - Buckle up for safety: A comment on Reynolds and Schiffbauer (2004).

PMID- 22478448
TI  - Focus on response rate is important but not sufficient: A reply.

PMID- 22478449
TI  - Why Morris, Lazo, and Smith (2004) was published in The Behavior Analyst.

PMID- 22478450
TI  - "Replacing" problem behavior: an analysis of tactical alternatives.
AB  - A number of textbooks and professional volumes in applied behavior analysis
      suggest that interventions designed primarily to decrease a problem behavior
      should routinely be accompanied by efforts to increase the frequency of at least
      one appropriate behavior. Some sources describe the objective of this tactic as
      "replacing" the problem behavior. This paper considers rationales that might
      underlie this advice, as well as reasons why a general rule to this effect is
      inappropriate. This review reveals that although there may well be good reasons
      for considering this tactic, their rationales are often not well articulated and
      may even be unsound. It is also the case that there are good reasons why this
      tactic may not always be necessary, thus conflicting with an argument for a
      general rule.

PMID- 22478451
TI  - Private stimuli, covert responses, and private events: conceptual remarks.
AB  - In this article, I discuss the concepts of private stimuli, covert responses, and
      private events, emphasizing three aspects: the conditions under which private
      stimuli may acquire discriminative functions to verbal responses, the conditions
      of unobservability of covert responses, and the complexity of events or phenomena
      described as private. I argue that the role of private stimuli in the control of
      self-descriptive verbal responses is dependent on a relation (correlation or
      equivalence relation) with public stimuli, and that responses vary along a
      continuum of observability. These remarks on private stimuli and covert responses
      are introductory to an examination of the varying complexity of phenomena
      described as private. I argue that private events is a verbal response emitted
      under the control of phenomena of different degrees of complexity, and I
      interpret these phenomena, based on the principle of selection by consequences. I
      introduce the notion of inclusiveness to suggest that some phenomena related to
      privacy are less or more complex as they include relations of a phylogenetic,
      ontogenetic, and cultural origin.

PMID- 22478452
TI  - Positive behavior support and applied behavior analysis.
AB  - This article reviews the origins and characteristics of the positive behavior
      support (PBS) movement and examines those features in the context of the field of
      applied behavior analysis (ABA). We raise a number of concerns about PBS as an
      approach to delivery of behavioral services and its impact on how ABA is viewed
      by those in human services. We also consider the features of PBS that have
      facilitated its broad dissemination and how ABA might benefit from emulating
      certain practices of the PBS movement.

PMID- 22478454
TI  - Linguistic Sources of Skinner's Verbal Behavior.
AB  - Formal and functional analyses of verbal behavior have been often considered to
      be divergent and incompatible. Yet, an examination of the history of part of the
      analytical approach used in Verbal Behavior (Skinner, 1957/1992) for the
      identification and conceptualization of verbal operant units discloses that it
      corresponds well with formal analyses of languages. Formal analyses have been
      carried out since the invention of writing and fall within the scope of
      traditional grammar and structural linguistics, particularly in analyses made by
      the linguist Leonard Bloomfield. The relevance of analytical instruments
      originated from linguistic studies (which examine and describe the practices of
      verbal communities) to the analysis of verbal behavior, as proposed by Skinner,
      relates to the conception of a verbal community as a prerequisite for the
      acquisition of verbal behavior. A deliberately interdisciplinary approach is
      advocated in this paper, with the systematic adoption of linguistic analyses and
      descriptions adding relevant knowledge to the design of experimental research in
      verbal behavior.

PMID- 22478455
TI  - Teaching the distinction between positive and negative reinforcement.

PMID- 22478456
TI  - Comment on baron and galizio (2005).

PMID- 22478453
TI  - Citation Analysis of Skinner's Verbal Behavior: 1984-2004.
AB  - The present study undertook an updated citation analysis of Skinner's
      (1957)Verbal Behavior. All articles that cited Verbal Behavior between 1984 and
      2004 were recorded and content analyzed into one of five categories; four
      empirical and one nonempirical. Of the empirical categories, studies that
      employed a verbal operant from Skinner's analysis were assigned to either basic,
      applied, or observational categories. Empirical studies that did not employ a
      verbal operant were categorized as other-empirical. The total number of citations
      remained stable across the review period and averaged just over 52 per year. Of
      these, 80% were from nonempirical articles, 13.7% were from other-empirical
      articles, 4% were from applied articles, 1.4% were from basic articles, and 0.9%
      were from observational articles. An "obliteration" analysis was also conducted
      to identify articles that employed Skinner's verbal operant terms but did not
      cite Verbal Behavior. This analysis identified 44 additional articles, suggesting
      that a degree of obliteration had occurred in the half century since the
      publication of Verbal Behavior. In particular, the analysis suggests that the
      verbal operant of manding has sufficient presence in the applied empirical
      literature to render citation of Verbal Behavior redundant. Overall, Verbal
      Behavior continues to make an important contribution to the psychological
      literature.

PMID- 22478457
TI  - On the distinction between positive and negative reinforcement.

PMID- 22478458
TI  - Through the looking glass: symmetry in behavioral principles?

PMID- 22478459
TI  - And Yet ...: Further Comments on distinguishing Positive and Negative
      Reinforcement.

PMID- 22478460
TI  - The distinction between positive and negative reinforcement: some additional
      considerations.

PMID- 22478461
TI  - The distinction between positive and negative reinforcement: use with care.
AB  - It is customary in behavior analysis to distinguish between positive and negative
      reinforcement in terms of whether the reinforcing event involves onset or offset
      of a stimulus. In a previous article (Baron & Galizio, 2005), we concluded that a
      distinction of these terms is not only ambiguous but has little if any functional
      significance. Here, we respond to commentaries by a group of distinguished
      behavior analysts about the issues we raised. Although several of the
      commentators argued for preservation of the distinction, we remain unconvinced
      that its benefits outweigh its weaknesses. Because this distinction is so deeply
      embedded in the language of behavior analysis, we hardly expect that it will be
      abandoned. However, we hope that the terms positive and negative reinforcement
      will be used with circumspection and with full knowledge of the confusion they
      can engender.

PMID- 22478462
TI  - Acceptance and commitment therapy and behavioral activation for the treatment of
      depression: description and comparison.
AB  - The field of clinical behavior analysis is growing rapidly and has the potential
      to affect and transform mainstream cognitive behavior therapy. To have such an
      impact, the field must provide a formulation of and intervention strategies for
      clinical depression, the "common cold" of outpatient populations. Two treatments
      for depression have emerged: acceptance and commitment therapy (ACT) and
      behavioral activation (BA). At times ACT and BA may suggest largely redundant
      intervention strategies. However, at other times the two treatments differ
      dramatically and may present opposing conceptualizations. This paper will compare
      and contrast these two important treatment approaches. Then, the relevant data
      will be presented and discussed. We will end with some thoughts on how and when
      ACT or BA should be employed clinically in the treatment of depression.

PMID- 22478463
TI  - Behaviorism, latent learning, and cognitive maps: needed revisions in
      introductory psychology textbooks.
AB  - This paper critically assesses the scholarship in introductory psychology
      textbooks in relation to the topic of latent learning. A review of the treatment
      of latent learning in 48 introductory psychology textbooks published between 1948
      and 2004, with 21 of these texts published since 1999, reveals that the
      scholarship on the topic of latent learning demonstrated in introductory
      textbooks warrants improvement. Errors that persist in textbooks include the
      assertion that the latent learning experiments demonstrate unequivocally that
      reinforcement was not necessary for learning to occur, that behavioral theories
      could not account for the results of the latent learning experiments, that B. F.
      Skinner was an S-R association behaviorist who argued that reinforcement is
      necessary for learning to occur, and that because behavioral theories (including
      that of B. F. Skinner) were unable explain the results of the latent learning
      experiments the cognitive map invoked by Edward Tolman is the only explanation
      for latent learning. Finally, the validity of the cognitive map is typically
      accepted without question. Implications of the presence of these errors for
      students and the discipline are considered. Lastly, remedies are offered to
      improve the scholarship found in introductory psychology textbooks.

PMID- 22478465
TI  - Fred s. Keller, a generalized conditioned reinforcer.

PMID- 22478464
TI  - Self-Editing: On the Relation Between behavioral and Psycholinguistic Approaches.
AB  - In Skinner's (1957) conceptual analysis, the process of self-editing is integral
      to the dynamic complexities of multiply determined verbal behavior, but the
      analysis has generated little in the way of an experimental analysis. The
      majority of scientific work on self-editing has taken place within linguistics
      and cognitive psycholinguistics. Here we compare and contrast behavioral and
      cognitive psycholinguistic approaches to self-editing, highlighting points of
      contact that can be identified despite fundamental differences in theoretical
      styles. We conclude that the two approaches are not mutually exclusive on all
      dimensions, and suggest that a consideration of cognitive psycholinguistic
      research may help to spur an experimental analysis of self-editing from a
      behavioral perspective.

PMID- 22478466
TI  - The Case Against B. F. Skinner 45 years Later: An Encounter with N. Chomsky.
AB  - Chomsky's (1959) review of Verbal Behavior (Skinner, 1957) has been hailed as the
      most influential document in the history of psychology. Although many rejoinders
      to Chomsky's review have been published, their impact has been minimal. Moreover,
      Chomsky has not answered them in detail. To invite Chomsky to revisit a number of
      matters concerning the review, he was interviewed. The principal topics addressed
      by Chomsky were (a) historical factors associated with behaviorism after World
      War II; (b) circumstances surrounding the preparation of the review; (c) likely
      compatibility between formal and functional analyses of language; and (d)
      Chomsky's current point of view on aspects of the content of his review and on
      the evolution of behavior analysis.

PMID- 22478467
TI  - On Chomsky's Appraisal of Skinner's Verbal Behavior: A Half Century of
      Misunderstanding.
AB  - The history of the writing of Verbal Behavior (Skinner, 1957), Chomsky's review
      (1959), and MacCorquodale's rebuttal (1970) are briefly summarized. Chomsky's
      recent reflections on his review are analyzed: Chomsky's refusal to acknowledge
      the review's errors or its aggressive tone is consistent with his polemical style
      but comes at a minor cost in consistency and plausibility. However, his remarks
      about the place of Skinner's work in science reveal misunderstandings so great
      that they undercut the credibility of the review substantially. The gradual
      growth in the influence of Skinner's book suggests that its legacy will endure.

PMID- 22478468
TI  - Speculation and explicit identification as judgmental standards for positive or
      negative reinforcement: a comment on.

PMID- 22478469
TI  - Positive and negative reinforcers: how about the second and third functions?

PMID- 22478470
TI  - Distinguishing between positive and negative reinforcement: responses to  and.

PMID- 22478471
TI  - What happened to analysis in applied behavior analysis?
AB  - This paper addresses the current help-oriented focus of researchers in applied
      behavior analysis. Evidence from a recent volume of JABA suggests that analytic
      behavior is at low levels in applied analysis while cure-help behavior is at high
      strength. This low proportion of scientific behavior is apparantly related to
      cure-help contingencies set by institutions and agencies of help and the
      editorial policies of JABA itself. These contingencies have favored the flight to
      real people and a concern with client gains, evaluation and outcome strategies
      rather than the analysis of contingencies of reinforcement controlling human
      behavior. In this regard, the paper documents the current separation of applied
      behavior analysis from the experimental analysis of behavior. There is limited
      use of basic principles in applied analysis today and almost no reference to the
      current research in the experimental analysis of behavior involving concurrent
      operants and adjunctive behavior. This divorce of applied behavior research and
      the experimental analysis of behavior will mitigate against progress toward a
      powerful technology of behavior. In order to encourage a return to analysis in
      applied research, there is a need to consider the objectives of applied behavior
      analysis. The original purpose of behavioral technology is examined and a re
      definition of the concept of "social importance" is presented which can direct
      applied researchers toward an analytic focus. At the same time a change in the
      publication policies of applied journals such as JABA toward analytic research
      and the design of new educational contingencies for students will insure the
      survival of analysis in applied behavior analysis.

PMID- 22478472
TI  - Creative behavior.

PMID- 22478473
TI  - Engineering technology and behavior analysis for interdisciplinary environmental
      protection.
AB  - Engineering strategies for saving environmental resources have been widespread.
      However, many of those engineering advances have not been widely accepted nor
      generally applied by large segments of the general population. This paper
      considers the need to examine behavioral/environmental variables in the
      application of engineering technology, with particular reference to specific
      behavioral strategies for encouraging the use of engineering technology from an
      interdisciplinary perspective. A model for the study of factors contributing to
      the solution of ecological/environmental problems is presented and examples of
      interdisciplinary research are described. The model implies a need for the
      examination of the effects of antecedent and consequent manipulation of a variety
      of variables including: behavioral, physiological, environmental, technical and
      legal conditions. It is concluded that while interdisciplinary research efforts
      between engineering technologists and behavioral analysts are necessary, they
      have not received sufficient attention in the literature nor have they focused on
      the comprehensive study of antecedents and consequences as they relate to
      ecological/environmental problems. Thus, an extended "family" of research efforts
      is important for the success of these efforts.

PMID- 22478474
TI  - Where have all the behaviorists gone?
AB  - Many of the world's current problems are the result of behavior, and traditional
      appeals to mental determinants are again proving inadequate. The time for a
      behavioristic alternative appears ripe, yet many behaviorists seem to be becoming
      less behavioristic and more mentalistic. When confronted with the complexity of
      human behavior many are resorting to the intellectual comfort and safety of
      mentalism. A recent example of this tendency (Schwartz et al, 1978) is presented
      and discussed. Additionally, speculations regarding the origins of the resurgence
      of mentalism are presented, and it is proposed that arranging histories which
      provide for more rigorous and lasting control of verbal behavior about behavior
      may serve to improve the situation.

PMID- 22478475
TI  - The discriminative stimulus or S(D).

PMID- 22478476
TI  - The species-specific behavior of ethologists.

PMID- 22478477
TI  - Flight from behavior analysis.

PMID- 22478478
TI  - Self-control revisited: Or why doesn't anyone actually read Skinner anymore?
AB  - Self-control continues to develop as a major source of explanatory concepts
      within cognitive behavior therapy. The recent history of self-control is
      reviewed, and three related areas of disagreement between radical behaviorists
      and cognitive behaviorists are discussed. The logical status of self
      reinforcement, reciprocity, and private events is examined and evaluated. This
      review suggests that a radical behavioral approach continues to offer psychology
      the most effective program for the analysis of behavior.

PMID- 22478479
TI  - Our most unforgettable character.

PMID- 22478480
TI  - Natural concepts and generalization classes.
AB  - The results of an experiment performed by Herrnstein, Loveland, and Cable (1976)
      show that pigeons possess concepts that are not based on common elements. The
      conclusion they draw from these results is that these concepts are largely
      determined by genetic factors. In the present paper it is argued that, at least
      for some of the concepts, the conclusion is incorrect. These concepts-called here
      uncommon generalization classes-were acquired by the pigeons as a consequence of
      certain experiences through which they went during the experiment. The discussion
      will also suggest the fruitfulness of replacing the vague and misleading notion
      of concept by the more adequate notion of generalization class.

PMID- 22478481
TI  - On citing the literature.
AB  - Some outlandish examples are used to support the argument that literature
      citations should be treated as references to documents and not references to
      individuals. Different consequences for scientific behavior are implicit in the
      alternative usages.

PMID- 22478482
TI  - Defining creativity.

PMID- 22478483
TI  - On the alleged incompatibility of analysis: A response to Pierce and Epling.

PMID- 22478484
TI  - Values and the scientific culture of behavior analysis.
AB  - As scientists and practitioners, behavior analysts must make frequent decisions
      that affect many lives. Scientific principles have been our guide as we work to
      promote effective action across a broad spectrum of cultural practices. Yet
      scientific principles alone may not be sufficient to guide our decision making in
      cases with potentially conflicting outcomes. In such cases, values function as
      guides to work through ethical conflicts. We will examine two ethical systems,
      radical behaviorism and functional contextualism, from which to consider the role
      of values in behavior analysis, and discuss potential concerns. Finally, we
      propose philosophical pragmatism, focusing on John Dewey's notions of community
      and dialogue, as a tradition that can help behavior analysts to integrate talk
      about values and scientific practices in ethical decision making.

PMID- 22478485
TI  - Neural events in the reinforcement contingency.
AB  - When neural events are analyzed as stimuli and responses, functional relations
      among them and among overt stimuli and responses can be unveiled. The integration
      of neuroscience and the experimental analysis of behavior is beginning to provide
      empirical evidence of involvement of neural events in the three-term contingency
      relating discriminative stimuli, responses, and consequences. This paper is aimed
      at highlighting exemplar instances in the development of this issue. It has long
      been known that the electrical stimulation of certain cerebral areas can have a
      reinforcing function. Extraordinary technological advances in recent years show
      that neural activity can be selected by consequences. For example, the activity
      of in vitro isolated neurons that receive dopamine as a reinforcer functions as a
      cellular analogue of operant conditioning. The in vivo activity of populations of
      neurons of rats and monkeys can be recorded on an instant-to-instant basis and
      can then be used to move mechanical arms or track a target as a function of
      consequences. Neural stimulation acts as a discriminative stimulus for operant
      responses that are in turn maintained by neural consequences. Together with
      investigations on the molecular basis of classical conditioning, those studies
      are examples of possibilities that are being created for the study of behavior
      environment interactions within the organism. More important, they show that, as
      an element in the three-term contingency, neural activity follows the same laws
      as other events.

PMID- 22478486
TI  - Galen: developer of the reversal design?
AB  - Galen, known to psychologists largely for his personality theory of the four
      temperaments, diagnosed the cause of a patient's symptoms with a form of reversal
      design long before its formal description (e.g., Sidman, 1960).

PMID- 22478487
TI  - Cultural materialism and behavior analysis: common problems and radical
      solutions.

PMID- 22478488
TI  - A threshold theory of the humor response.
AB  - The humor response has long been considered mysterious, and it is given
      relatively little attention in modern experimental psychology, in spite of the
      fact that numerous studies suggest that it has substantial benefits for mood and
      health. Existing theories of humor fail to account for some of the most basic
      humor phenomena. On most occasions when a humor response occurs, certain verbal
      or visual stimuli (the "setup" stimuli, which function as an establishing
      operation) must precede a critical stimulus (such as a "punch line" or the final
      panel or critical feature of a cartoon), which then occasions a sudden
      "revelation" or "understanding"; this revelation is often accompanied by the
      humor response. We suggest that the setup stimuli increase the strength of the
      revelatory response to a point just below the threshold of awareness and that the
      critical stimulus, properly designed and timed, edges the revelatory response to
      a point just above threshold. We also suggest that it is this threshold
      phenomenon that produces most instances of the humor response. We discuss these
      issues in the context of some notable humor of Carl Rogers and B. F. Skinner.

PMID- 22478489
TI  - Ultimate realities: deterministic and evolutionary.
AB  - References to ultimate reality commonly turn up in the behavioral literature as
      references to determinism. However, this determinism is often difficult to
      interpret. There are different kinds of determinisms as well as different kinds
      of ultimate realities for a behaviorist to consider. To clarify some of the
      issues involved, the views of ultimate realities are treated as falling along a
      continuum, with extreme views of complete indeterminism and complete determinism
      at either end and various mixes in between. Doing so brings into play
      evolutionary realities and the movement from indeterminism to determinism, as in
      Peirce's evolutionary cosmology. In addition, this framework helps to show how
      the views of determinism by B. F. Skinner and other behaviorists have shifted
      over time.

PMID- 22478490
TI  - B. F. Skinner and T. N. Whitehead: a brief encounter, research similarities,
      hawthorne revisited, what next?
AB  - B. F. Skinner and T. N. Whitehead recalled a personal interaction in 1934, with
      differing memories of the event. No evidence of other subsequent interactions or
      mutual citations has been found. Although they went their separate ways, three
      similarities in their research strategies have been found and are discussed.
      Elements of Whitehead's Hawthorne study and Skinner's concurrent, parallel work
      reveal that they both (a) introduced the cumulative curve to report data, (b)
      used a small number of subjects studied over time, and (c) used highly accurate
      recording devices. A few "afterwords" are offered on their lives and writings,
      and again, on the Hawthorne effect. A suggestion is made that a Skinner-Whitehead
      research approach might be useful in studying gambling behavior.

PMID- 22478491
TI  - Positive behavior support: considerations for the future of a model.

PMID- 22478492
TI  - Trends in presentations at the annual conference of the association for behavior
      analysis.
AB  - The present report analyzes trends in attendance and presentations at the annual
      conference of the Association for Behavior Analysis (ABA). Numbers of registered
      attendees were plotted over time. The trends show that the number of registered
      attendees has grown considerably over the last three decades, with the largest
      proportion of the growth occurring during the last 10 years. This growth is shown
      to be correlated with the introduction of board certification in behavior
      analysis (BCBA and BCABA). In addition, conference programs from 1980 through
      2007 were coded, and all presentations were categorized into one of four areas
      (application, basic research, conceptual, and verbal behavior) based on the
      primary designator codes chosen by the authors at the time of submission. An
      analysis of the total number of presentations in each category indicates that
      applied research presentations have always outnumbered the other three
      categories. The absolute number of presentations related to application has grown
      faster than presentations in other categories. However, correcting for population
      growth shows that the relative proportion of presentations in the four areas has
      remained fairly constant over the last 28 years.

PMID- 22478493
TI  - The Influence of Bloomfield's Linguistics on Skinner.
AB  - Bloomfield's "Linguistics as a Science" (1930/1970), Language (1933/1961), and
      "Language or Ideas?" (1936a/1970), and Skinner's Verbal Behavior (1957) and
      Science and Human Behavior (1953) were analyzed in regard to their respective
      perspectives on science and scientific method, the verbal episode, meaning, and
      subject matter. Similarities between the two authors were found. In particular
      both asserted that (a) the study of language must be carried out through the
      methods of science; (b) the main function of language is to produce practical
      effects on the world through the mediation of a listener; and (c) a physicalist
      conception of meaning. Their differences concern the subject matter of their
      disciplines and their use of different models for the analysis of behavior.
      Bloomfield's linguistics and Skinner's functional analysis of verbal behavior are
      complementary approaches to language.

PMID- 22478494
TI  - The ultimate challenge: prove B. F. Skinner wrong.
AB  - For much of his career, B. F. Skinner displayed the optimism that is often
      attributed to behaviorists. With time, however, he became less and less sanguine
      about the power of behavior science to solve the major problems facing humanity.
      Near the end of his life he concluded that a fair consideration of principles
      revealed by the scientific analysis of behavior leads to pessimism about our
      species. In this article I discuss the case for Skinner's pessimism and suggest
      that the ultimate challenge for behavior analysts today is to prove Skinner
      wrong.

PMID- 22478495
TI  - A transactional systems model of autism services.
AB  - There has been an escalation in the number of children identified with autism
      spectrum disorders in recent years. To increase the likelihood that treatments
      for these children are effective, interventions should be derived from sound
      theory and research evidence. Absent this supportive foundation, intervention
      programs could be inconsequential if not harmful. Although atypical, the
      development of children with autism should be considered initially from the
      perspective of the same variables that affect the development of typical
      children. In addition, the developmental deviations that characterize autism must
      be considered when developing intervention programs. Behavioral systems models
      describe both typical and atypical development and emphasize dynamic
      multidirectional person-environment transactions. The environment is viewed as
      having multiple levels, from the individuals with autism themselves, to larger
      societal and cultural levels. Behavioral systems models of human development can
      be generalized to a transactional systems model of services for children with
      autism. This model is the foundational theoretical position of the Southern
      Illinois University Center for Autism Spectrum Disorders. The center's programs
      are described to illustrate the application of the model to multiple levels of
      the social ecology.

PMID- 22478496
TI  - Trends in Women's Participation at the Meetings of the Association for Behavior
      Analysis: 1975-2005.
AB  - We examined women's participation, relative to men's, at the annual meetings of
      the Association for Behavior Analysis (ABA) between 1975 and 2005. Among our
      findings are upward trends in female presenters across formats (e.g., posters),
      types of authorship (e.g., first authors), and specialty areas (e.g., autism).
      Where women have attained parity, however, they are still often underrepresented,
      given their percentage of membership. Women also participate less than men as
      sole and invited authors and discussants and in the domains of basic research and
      conceptual analysis, but participate more than men in the applied domain. Data
      from the Journal of the Experimental Analysis of Behavior and the Journal of
      Applied Behavior Analysis show parallel but delayed trends toward parity in basic
      and applied research, whereas data from The Behavior Analyst show only modest
      gains in the conceptual domain. We discuss the gender disparities in ABA's more
      prestigious categories of participation (e.g., invited addresses) and across its
      content domains, as well as in science in general, and the role of social and
      cultural factors in producing the disparities and how behavior analysts might aid
      in correcting them.

PMID- 22478498
TI  - Some comments on the distinction between intention and intentionality.
AB  - The topic of intention has recently received attention from behavior analysts
      (Hineline, 2003; Neuman, 2004). From a behavior-analytic perspective, it is
      important to identify the circumstances in which people utter such terms, and to
      identify the potential circumstances that maintain such utterances. It follows
      that from a behavior-analytic perspective, the focus is primarily on those who
      observe behavior and attribute intentions to that behavior. However, there has
      not been a distinction between intention and intentionality. The current analysis
      stresses the distinction between the two terms, both from a traditional point of
      view (psychologist and layperson) and from a behavior-analytic point of view.
      From a behavior analyst's perspective, the distinction is important because
      observers may be responding to distinct functional relations when they attribute
      intention or intentionality to behavior.

PMID- 22478497
TI  - Extended Analysis of Empirical Citations with Skinner's Verbal Behavior: 1984
      2004.
AB  - The present paper comments on and extends the citation analysis of verbal operant
      publications based on Skinner's Verbal Behavior (1957) by Dymond, O'Hora, Whelan,
      and O'Donovan (2006). Variations in population parameters were evaluated for only
      those studies that Dymond et al. categorized as empirical. Preliminary results
      indicate that the majority of empirical research in the area of verbal behavior
      has been conducted with the younger developmentally disabled population and has
      focused on verbal operants from the introductory chapters of Skinner's book. It
      is clear that Verbal Behavior has influenced empirical research over the past 50
      years. We believe, however, that there are many underdeveloped research areas
      originating from Verbal Behavior that have not yet been addressed. Suggestions
      for extended areas of research are provided.

PMID- 22478499
TI  - The nature of clinical depression: symptoms, syndromes, and behavior analysis.
AB  - In this article we discuss the traditional behavioral models of depression and
      some of the challenges analyzing a phenomenon with such complex and varied
      features. We present the traditional model and suggest that it does not capture
      the complexity of the phenomenon, nor do syndromal models of depression that
      dominate the mainstream conceptualization of depression. Instead, we emphasize
      ideographic analysis and present depression as a maladaptive dysregulation of an
      ultimately adaptive elicited emotional response. We emphasize environmental
      factors, specifically aversive control and private verbal events, in terms of
      relational frame theory, that may transform an adaptive response into a
      maladaptive disorder. We consider the role of negative thought processes and
      rumination, common and debilitating aspects of depression that have traditionally
      been neglected by behavior analysts.

PMID- 22478500
TI  - Behavioral contributions to teaching of psychology: an annotated bibliography.
AB  - An annotated bibliography that summarizes behavioral contributions to the journal
      Teaching of Psychology from 1974 to 2006 is provided. A total of 116 articles of
      potential utility to college-level instructors of behavior analysis and related
      areas were identified, annotated, and organized into nine categories for ease of
      accessibility.

PMID- 22478502
TI  - An initial survey of fractional graph and table area in behavioral journals.
AB  - This study examined the fractional graph area (FGA), the proportion of page space
      used to display statistical graphics, in 11 behavioral journals and places
      behavior analysis on a continuum with other natural, mathematical, and social
      science disciplines. The composite FGA of all 11 journals puts behavior analysis
      within the range of the social sciences, whereas the composite FGA of the most
      established and preeminent behavioral journals positions behavior analysis within
      the range of the natural sciences. In addition, fractional table area (FTA), the
      proportion of page space used to display tables, generally is higher in
      behavioral journals with lower degrees of FGA, a result that replicates previous
      research.

PMID- 22478501
TI  - What 50 years of research tell us about pausing under ratio schedules of
      reinforcement.
AB  - Textbooks in learning and behavior commonly describe performance on fixed-ratio
      schedules as "break and run," indicating that after reinforcement subjects
      typically pause and then respond quickly to the next reinforcement. Performance
      on variable-ratio schedules, on the other hand, is described as steady and fast,
      with few long pauses. Beginning with Ferster and Skinner's magnum opus, Schedules
      of Reinforcement (1957), the literature on pausing under ratio schedules has
      identified the influences on pausing of numerous important variables, in
      particular ratio size and reinforcement magnitude. As a result, some previously
      held assumptions have been called into question. For example, research has shown
      that the length of the pause is controlled not only by the preceding ratio, as
      Ferster and Skinner and others had assumed (and as implied by the phrase
      postreinforcement pause), but by the upcoming ratio as well. Similarly, despite
      the commonly held belief that ratio pausing is unique to the fixed-ratio
      schedule, there is evidence that pausing also occurs under variable-ratio
      schedules. If such widely held beliefs are incorrect, then what about other
      assumptions? This article selectively examines the literature on pausing under
      ratio schedules over the past 50 years and concludes that although there may
      indeed be some common patterns, there are also inconsistencies that await future
      resolution. Several accounts of pausing under ratio schedules are discussed along
      with the implications of the literature for human performances, most notably the
      behaviors termed procrastination.

PMID- 22478503
TI  - Culture-sensitive functional analytic psychotherapy.
AB  - Functional analytic psychotherapy (FAP) is defined as behavior-analytically
      conceptualized talk therapy. In contrast to the technique-oriented educational
      format of cognitive behavior therapy and the use of structural mediational
      models, FAP depends on the functional analysis of the moment-to-moment stream of
      interactions between client and therapist. This distinctive feature makes FAP
      particularly sensitive to the challenges posed by cultural differences between
      client and therapist. Core elements of FAP philosophy are invoked to argue that
      this vulnerability paradoxically implies an increased ability to capture and use
      relevant issues in the therapy process with culturally different clients. This
      argument focuses FAP's preference for concrete behavior over theoretical
      modeling, its emphasis on functional principles rather than topographically
      defined techniques, and its inclusion of the therapist's behavior in the
      assessment of clients' clinically relevant behavior. Suggestions are given
      concerning how academic and practical training and personal experience may be
      used to foster sound multicultural practice.

PMID- 22478504
TI  - Introduction: 2008 state of the science lectures.

PMID- 22478505
TI  - Stimuli, reinforcers, and private events.
AB  - Radical behaviorism considers private events to be a part of ongoing observable
      behavior and to share the properties of public events. Although private events
      cannot be measured directly, their roles in overt action can be inferred from
      mathematical models that relate private responses to external stimuli and
      reinforcers according to the same quantitative relations that characterize public
      operant behavior. This approach is illustrated by a model of attending to stimuli
      and to anticipated reinforcers in delayed matching to sample, in which the
      probabilities of attending are related to reinforcer rates by an expression
      derived from research on behavioral momentum.

PMID- 22478506
TI  - Reflections on stimulus control.
AB  - The topic of stimulus control is too broad and complex to be traceable here. It
      would probably take a two-semester course to cover just the highlights of that
      field's evolution. The more restricted topic of equivalence relations has itself
      become so broad that even an introductory summary requires more time than we have
      available. An examination of relations between equivalence and the more general
      topic of stimulus control, however, may reveal characteristics of both the larger
      and the more limited field that have not been generally discussed. Consideration
      of these features may in turn foster future developments within each area. I
      speak, of course, about aspects of stimulus control that my own experiences have
      made salient to me; others would surely emphasize different characteristics of
      the field. It is my hope that cooperative interactions among researchers and
      theorists who approach stimulus control from different directions will become
      more common than is currently typical.

PMID- 22478507
TI  - Self-awareness: behavior analysis and neuroscience.
AB  - Self-awareness is a specific type of autoclitic discriminative behavior and
      inferential generalization to similar performances exhibited by other people.
      Brain imaging findings take on special importance within behavior analysis when
      they indicate that dysfunctions in these areas are related to differential
      effects of our interventions, with some acquiring substantially typical self
      awareness skills and others failing to do so. It appears that those individuals
      whose brain dysfunctions are limited to these areas, and are not part of more
      generalized brain abnormalities, are amenable to substantial acquisition of those
      most basic of human skills called self-awareness, whereas individuals with more
      generalized brain dysfunction are not so disposed. Through a combination of less
      or more effective teaching contingencies during childhood, and degrees of
      dysfunction of those brain structures, some children grow up lacking self
      reflective abilities and self-insight, whereas others are extraordinarily astute
      at those capacities. Among children with autism spectrum disorders who lack those
      skills due to abnormal brain development, approximately half of them can acquire
      those skills, at least to some degree through the use of effective, intensive,
      early behavior therapy methods.

PMID- 22478508
TI  - Listening is behaving verbally.
AB  - As we celebrate the 50th anniversary of the publication of B. F. Skinner's Verbal
      Behavior, it may be important to reconsider the role of the listener in the
      verbal episode. Although by Skinner's own admission, Verbal Behavior was
      primarily about the behavior of the speaker, his definition of verbal behavior as
      "behavior reinforced through the mediation of other persons" (1957, p. 2) focused
      on the behavior of the listener. But because many of the behaviors of the
      listener are fundamentally no different than other discriminated operants, they
      may not appropriately be termed listening. Even Skinner noted that the behavior
      of the listener often goes beyond simply mediating consequences for the speaker's
      behavior, implying that the listener engages in a repertoire of behaviors that is
      itself verbal. In the present article I suggest that listening involves subvocal
      verbal behavior. I then describe some of the forms and functions of the
      listener's verbal behavior (including echoic and intraverbal behavior) and
      conclude that there may be no functional distinction between speaking and
      listening.

PMID- 22478509
TI  - Radical behaviorism and buddhism: complementarities and conflicts.
AB  - Comparisons have been made between Buddhism and the philosophy of science in
      general, but there have been only a few attempts to draw comparisons directly
      with the philosophy of radical behaviorism. The present review therefore
      considers heretofore unconsidered points of comparison between Buddhism and
      radical behaviorism in terms of their respective goals, conceptualization of
      human beings, and the outcomes of following either philosophy. From these
      comparisons it is concluded that the commonalities discerned between these two
      philosophies may enhance both philosophical systems.

PMID- 22478510
TI  - Sidney w. Bijou: the illinois years, 1965-1975.
AB  - Sidney W. Bijou is among the founders of behavior analysis, but the record of his
      contributions is incomplete. It has not systematically described his
      contributions beyond his tenure at the University of Washington (1948-1965). The
      purpose of this paper is to describe his contributions over the course of the
      next decade-his years at the University of Illinois (1965-1975). I begin by
      reviewing his education and training, contributions at Washington, and why he
      left and moved to Illinois. Then, I describe his Illinois years: his
      appointments, colleagues, and service; the Child Behavior Laboratory; grant
      funding and publications; further service, awards, and recognition; and influence
      on his colleagues, students, classroom teachers and research supervisors, and
      visiting scholars. Bijou is modest about his contributions at Illinois, but he
      advanced the field in many ways over the course of the decade, especially the
      careers of his colleagues and students.

PMID- 22478511
TI  - A contemporary behavior analysis of anxiety and avoidance.
AB  - Despite the central status of avoidance in explaining the etiology and
      maintenance of anxiety disorders, surprisingly little behavioral research has
      been conducted on human avoidance. In the present paper, first we provide a brief
      review of the empirical literature on avoidance. Next, we describe the
      implications of research on derived relational responding and the transformation
      of functions for a contemporary behavioral account of avoidance, before providing
      several illustrative research examples of laboratory-based analogues of key
      clinical treatment processes. Finally, we suggest some challenges and
      opportunities that lie ahead for behavioral research on anxiety and avoidance.

PMID- 22478512
TI  - A behavior-analytic account of cognitive bias in clinical populations.
AB  - Cognitive bias refers to a well-established finding that individuals who suffer
      from certain clinical problems (e.g., depression, anxiety, posttraumatic stress
      disorder, substance abuse, etc.) selectively attend to, remember, and interpret
      events relevant to their condition. Although a body of literature exists that has
      tried to examine this phenomenon, most existing explanations are mentalistic and
      mediational. In this paper we offer a behavior-analytic account of cognitive
      bias, its development, and how it may contribute to maintenance of clinical
      problems. This account is based on establishing operations or motivating events,
      verbal processes, and relational responding. Clinical and future research
      implications are also discussed.

PMID- 22478513
TI  - Molar functional relations and clinical behavior analysis: implications for
      assessment and treatment.
AB  - The experimental analysis of behavior has identified several molar functional
      relations that are highly relevant to clinical behavior analysis. These include
      matching, discounting, momentum, and variability. Matching provides a broader
      analysis of how multiple sources of reinforcement influence how individuals
      choose to allocate their time and offers an empirical rationale for reducing
      problem behavior by increasing adaptive behavior. Discounting highlights the
      functional relations that affect self-control. Momentum specifies the variables
      responsible for persistence in challenging situations. Variability characterizes
      a functional dimension of behavior that is essential for learning and problem
      solving. These concepts have important implications for clinical practice and
      research. A selective review of these concepts is presented, and their
      implications for assessment and treatment are discussed with two goals: to inform
      basic scientists about the relevance of their work and to invite clinical
      behavior analysts to broaden the conceptual basis for their work.

PMID- 22478514
TI  - Beyond values clarification: addressing client values in clinical behavior
      analysis.
AB  - Ethical principles of psychology, as exemplified in the American Psychological
      Association (APA) Code of Ethics (2002), provide impractical advice for
      addressing client values during psychotherapy. These principles seem to argue
      that each client's values should be respected and protected at all times, except
      in cases in which this would result in harm to the client or the general public.
      Although the code is appropriately designed as a defense against potential and
      actual abuses of professional power, this general proscription against directly
      targeting client values for change is based on an understanding of values that
      grants them special ontological status and has resulted in limited clinical
      interventions focusing solely on "values clarification." With its strong
      foundation in a unified philosophical system, clinical behavior analysis offers a
      sophisticated alternative approach to values that both defines what they are and
      identifies when they can be ethically targeted to improve the lives of clients.

PMID- 22478515
TI  - In search of meaning: values in modern clinical behavior analysis.
AB  - Skinner described behavior analysis as the field of values and purpose. However,
      he defined these concepts in terms of a history of reinforcement and failed to
      specify whether and how human and nonhuman values might differ. Human values have
      been seen as theoretically central within a number of nonbehavioral traditions in
      psychology, including humanism and positive psychology. However, these approaches
      have failed to provide explanations of the behavior-environment relations
      involved in valuing that might allow prediction and influence with respect to
      this phenomenon. Modern clinical behavior analysis in the form of acceptance and
      commitment therapy (ACT), however, succeeds in providing a functional definition
      of human values that meets this latter criterion. ACT is rooted in behavior
      analysis and relational frame theory (RFT) and defines values in terms of
      verbally established motivation. ACT empirical research into values has begun to
      blossom in recent years, and ACT-RFT researchers are currently investigating the
      concept at the most basic empirical level as well as in the applied clinical
      arena, heralding new interest in and insight into values within clinical
      behavioral psychology.

PMID- 22478517
TI  - The challenge of understanding process in clinical behavior analysis: the case of
      functional analytic psychotherapy.
AB  - Whether explicitly acknowledged or not, behavior-analytic principles are at the
      heart of most, if not all, empirically supported therapies. However, the change
      process in psychotherapy is only now being rigorously studied. Functional
      analytic psychotherapy (FAP; Kohlenberg & Tsai, 1991; Tsai et al., 2009)
      explicitly identifies behavioral-change principles used to bring about
      therapeutic improvements in adult outpatients whose clinical problems stem from
      ineffective interpersonal repertoires. These principles include contingent
      responding to behavioral excesses and deficits by a therapist who has established
      him- or herself as a salient source of social reinforcement. Empirical support
      for FAP is emerging, but a variety of pragmatic and theoretical questions warrant
      investigation. Among the issues described in this paper are the training and
      dissemination of procedures for how to conduct a functional analysis, how to
      train therapists to identify functional stimulus classes, how to best address
      decreasing problem behavior without creating an aversive environment, how to
      enhance generalization, and how to account for the principle of equifinality when
      trying to specify therapeutic procedures. These and other issues stem largely
      from trying to disseminate a behavioral principle-based intervention rather than
      a topographically specified intervention. These issues present challenges and
      research opportunities for applied clinical behavior analysts if they wish to
      extend their science to address clinical issues important to the treatment of
      adult outpatients with normal intellectual functioning.

PMID- 22478516
TI  - Creating a strategy for progress: a contextual behavioral science approach.
AB  - Behavior analysis is a field dedicated to the development and application of
      behavioral principles to the understanding and modification of the psychological
      actions of organisms. As such, behavior analysis was committed from the beginning
      to a comprehensive account of behavior, stretching from animal learning to
      complex human behavior. Despite that lofty goal, basic behavior analysis is
      having a generally harder time finding academic support, and applied behavior
      analysis has narrowed its focus. In the present paper we argue that both of these
      trends relate to the challenge of human language and cognition, and that
      developments within clinical behavior analysis and the analysis of derived
      relational responding are providing a way forward. To take full advantage of
      these developments, however, we argue that behavior analysts need to articulate
      their unique approach to theory, to develop more flexible language systems for
      applied workers, and to expand their methodological flexibility. This approach,
      which we term contextual behavioral science, is meant as an evolutionary step
      that will allow behavior analysis to better capture the center of modern
      psychological concerns in both the basic and applied areas. Clinical behavior
      analysis is showing a way forward for behavior analysis to regain its vision as a
      comprehensive approach to behavior.

PMID- 22478518
TI  - A behavior-analytic account of motivational interviewing.
AB  - Several published reports have now documented the clinical effectiveness of
      motivational interviewing (MI). Despite its effectiveness, there are no generally
      accepted or empirically supported theoretical accounts of its effects. The
      theoretical accounts that do exist are mentalistic, descriptive, and not based on
      empirically derived behavioral principles. Empirical research is being generated
      regarding the role of client and therapist verbal behavior in MI. Client and
      therapist speech in MI sessions has been correlated with subsequent client
      behavior change (Amrhein, Miller, Yahne, & Fulcher, 2003; Gaume, Gmel, & Daeppen,
      2008; Moyers et al., 2007). Although provocative, these findings are
      correlational and no theory has yet been provided to explain them. The purposes
      of the present paper are (a) to bring MI to the attention of clinical behavior
      analysts; (b) to provide a conceptual account of MI that relies on recent
      developments in the behavior analysis of motivation and verbal behavior,
      especially stimulus equivalence and transformation of functions; (c) to provide a
      possible answer to two critical questions: "How does MI evoke client in-session
      talk abut behavior change?" and "Why is this change talk related to outcomes?";
      and (d) to use this account to identify important research questions and perhaps
      enhance MI's effectiveness.

PMID- 22478519
TI  - The search for an effective clinical behavior analysis: the nonlinear thinking of
      Israel goldiamond.
AB  - This paper has two purposes; the first is to reintroduce Goldiamond's
      constructional approach to clinical behavior analysis and to the field of
      behavior analysis as a whole, which, unfortunately, remains largely unaware of
      his nonlinear functional analysis and its implications. The approach is not
      simply a set of clinical techniques; instead it describes how basic, applied, and
      formal analyses may intersect to provide behavior-analytic solutions where the
      emphasis is on consequential selection. The paper takes the reader through a
      cumulative series of explorations, discoveries, and insights that hopefully
      brings the reader into contact with the power and comprehensiveness of
      Goldiamond's approach, and leads to an investigation of the original works cited.
      The second purpose is to provide the context of a life of scientific discovery
      that attempts to elucidate the variables and events that informed one of the most
      extraordinary scientific journeys in the history of behavior analysis, and expose
      the reader (especially young ones) to the exciting process of discovery followed
      by one of the field's most brilliant thinkers. One may perhaps consider this
      article a tribute to Goldiamond and his work, but the tribute is really to the
      process of scientific discovery over a professional lifetime.

PMID- 22478520
TI  - Much Ado About Nothing? Some Comments on B. F. Skinner's Definition of Verbal
      Behavior.
AB  - Some have suggested that the definition of verbal behavior offered by B. F.
      Skinner (1957) fails to capture the essence of language insofar as it is too
      broad and not functional. In this paper, I argue that the ambiguities of
      Skinner's definition are not an indictment of it, and that suggestions to the
      contrary are problematic because they suffer a critical error of scientific
      reasoning. Specifically, I argue that (a) no clear definition of verbal behavior
      is possible because there is no natural distinction between verbal and nonverbal
      behavior; (b) attempts at an immutable definition are essentialistic; and (c)
      Skinner's functional taxonomy of language is in no way affected by the
      particulars of any definition of verbal behavior.

PMID- 22478521
TI  - Religion as schedule-induced behavior.
AB  - In this article, I argue that a class of religious behaviors exists that is
      induced, for prepared organisms, by specific stimuli that are experienced
      according to a response-independent schedule. Like other schedule-induced
      behaviors, the members of this class serve as minimal units out of which
      functional behavior may arise. In this way, there exist two classes of religious
      behavior: nonoperant schedule-induced behaviors and operant behaviors. This
      dichotomy is consistent with the distinction insisted upon by religious scholars
      and philosophers between "graceful" and "effortful" religious behaviors.
      Embracing the distinction allows an explanation of many aspects of religious
      experience and behavior that have been overlooked or disregarded by other
      scientific approaches to religion.

PMID- 22478523
TI  - A Response to Diller and Lattal's "Radical Behaviorism and Buddhism".

PMID- 22478524
TI  - A Comprehensive Science: A Review of Moore's Conceptual Foundations of Radical
      Behaviorism.

PMID- 22478525
TI  - Introduction: translational science lectures.

PMID- 22478522
TI  - A case study in the misrepresentation of applied behavior analysis in autism: the
      gernsbacher lectures.
AB  - I know that most men, including those at ease with problems of the greatest
      complexity, can seldom accept the simplest and most obvious truth if it be such
      as would oblige them to admit the falsity of conclusions which they have proudly
      taught to others, and which they have woven, thread by thread, into the fabrics
      of their life. (Tolstoy, 1894)This article presents a case study in the
      misrepresentation of applied behavior analysis for autism based on Morton Ann
      Gernsbacher's presentation of a lecture titled "The Science of Autism: Beyond the
      Myths and Misconceptions." Her misrepresentations involve the characterization of
      applied behavior analysis, descriptions of practice guidelines, reviews of the
      treatment literature, presentations of the clinical trials research, and
      conclusions about those trials (e.g., children's improvements are due to
      development, not applied behavior analysis). The article also reviews applied
      behavior analysis' professional endorsements and research support, and addresses
      issues in professional conduct. It ends by noting the deleterious effects that
      misrepresenting any research on autism (e.g., biological, developmental,
      behavioral) have on our understanding and treating it in a transdisciplinary
      context.

PMID- 22478526
TI  - Translational behavior analysis: from laboratory science in stimulus control to
      intervention with persons with neurodevelopmental disabilities.
AB  - Throughout its history, laboratory research in the experimental analysis of
      behavior has been successful in elucidating and clarifying basic learning
      principles and processes in both humans and nonhumans. In parallel, applied
      behavior analysis has shown how fundamental behavior-analytic principles and
      procedures can be employed to promote desirable forms of behavior and to prevent
      or ameliorate undesirable forms in clinical, educational, and other settings.
      Less obviously, there has also emerged a small but identifiable bridging field
      that can potentially connect and inform both basic and applied behavior analysis.
      Although such translational behavior analysis uses laboratory methodologies,
      research targets are selected largely for their value in ultimate application to
      improve the human condition. I will discuss the distinction of translational
      behavior analysis from basic and applied behavior analysis and consider the
      potential contribution that translational research can make in the development of
      the science of behavior.

PMID- 22478527
TI  - Antecedent stimulus control: using orienting cues to facilitate first-word
      acquisition for nonresponders with autism.
AB  - Although considerable progress has been made in improving the acquisition of
      expressive verbal communication in children with autism, research has documented
      that a subpopulation of children still fail to acquire speech even with intensive
      intervention. One variable that might be important in facilitating responding for
      this nonverbal subgroup of children is the use of antecedent orienting cues.
      Using a multiple baseline design, this study examined whether individualized
      orienting cues could be identified, and whether their presentation would result
      in the production of verbal expressive words. The results showed that this
      antecedent stimulus control procedure produced improvements in responding to
      verbal models in all of the children, and subsequent gains in speech for some of
      the children. Theoretical and applied implications of orienting cues as they
      relate to antecedent stimulus control for children with autism are discussed.

PMID- 22478528
TI  - The Persistence-Strengthening Effects of DRA: An Illustration of Bidirectional
      Translational Research.
AB  - We summarize a series of bidirectional research studies that demonstrate the
      persistence-strengthening effects of differential reinforcement of alternative
      behavior on problem behavior. We model a possible solution to this problem with
      rats followed by replication with a human clinical population. The importance of
      coordinated basic and applied research to stimulate new behavioral technologies
      is emphasized.

PMID- 22478529
TI  - Response persistence: the effects of stimulus control on negatively reinforced
      problem behavior in a concurrent operant.
AB  - In the context of instructional demands, compliance and problem behavior can be
      considered concurrent operants. Of applied interest is increasing one response
      (i.e., compliance) while decreasing the other (i.e., problem behavior). Strategic
      arrangement of reinforcement can alter response allocation accordingly. Such
      schedules can also influence response persistence and generalization. A case
      study is used to illustrate the effects of stimulus-reinforcer relations in a
      concurrent-operants arrangement involving an adult with developmental
      disabilities and problem behavior. Results are discussed in the context of basic
      operant research findings in the areas of stimulus control and behavioral
      persistence.

PMID- 22478530
TI  - Relational responding and conditional discrimination procedures: an apparent
      inconsistency and clarification.
AB  - This article discusses theoretical issues relating to an apparent terminological
      inconsistency between two recent studies involving relational responding. These
      studies employed a functionally similar protocol to establish contextual cues for
      arbitrarily applicable relational responding by using a nonarbitrary relational
      responding procedure; however, one employed the term nonarbitrary regarding this
      procedure, and the other used arbitrary. Both can be legitimately described as
      correct, but they use apparently contradictory descriptions because they focus on
      different aspects of the protocol; in one, the label is based on traditional
      conditional discrimination task nomenclature, whereas in the other, it is based
      on the type of relational responding being performed. The current article
      describes and then explains the issue. In doing so, it touches on an important
      topic concerning the relation between relational responding and the conditional
      discrimination procedure.

PMID- 22478532
TI  - Kathleen kinkade.

PMID- 22478531
TI  - B. F. Skinner's Utopian Vision: Behind and Beyond Walden Two.
AB  - This paper addresses B. F. Skinner's utopian vision for enhancing social justice
      and human well-being in his 1948 novel, Walden Two. In the first part, we situate
      the book in its historical, intellectual, and social context of the utopian
      genre, address critiques of the book's premises and practices, and discuss the
      fate of intentional communities patterned on the book. The central point here is
      that Skinner's utopian vision was not any of Walden Two's practices, except one:
      the use of empirical methods to search for and discover practices that worked. In
      the second part, we describe practices in Skinner's book that advance social
      justice and human well-being under the themes of health, wealth, and wisdom, and
      then show how the subsequent literature in applied behavior analysis supports
      Skinner's prescience. Applied behavior analysis is a measure of the success of
      Skinner's utopian vision: to experiment.

PMID- 22478533
TI  - What are we doing when we translate from quantitative models?
AB  - Although quantitative analysis (in which behavior principles are defined in terms
      of equations) has become common in basic behavior analysis, translational efforts
      often examine everyday events through the lens of narrative versions of
      laboratory-derived principles. This approach to translation, although useful, is
      incomplete because equations may convey concepts that are difficult to capture in
      words. To support this point, we provide a nontechnical introduction to selected
      aspects of quantitative analysis; consider some issues that translational
      investigators (and, potentially, practitioners) confront when attempting to
      translate from quantitative models; and discuss examples of relevant
      translational studies. We conclude that, where behavior-science translation is
      concerned, the quantitative features of quantitative models cannot be ignored
      without sacrificing conceptual precision, scientific and practical insights, and
      the capacity of the basic and applied wings of behavior analysis to communicate
      effectively.

PMID- 22478534
TI  - How to discover what you have to say-a talk to students.

PMID- 22478535
TI  - Behavior modification and human rights: A legacy of Edward Stanton Sulzer, 1930
      1970.
AB  - Edward Stanton Sulzer was born in New York City on June 4, 1930. He attended
      school in Laureltown, N.Y., until the age of 15, when, after two years of high
      school, he was admitted into the University of Chicago. Leaving prematurely due
      to his mother's death, he returned to New York to work in film production. Sulzer
      completed his undergraduate work at the City College of New York, studying film
      production and psychology. In 1953 he entered the doctoral program in clinical
      psychology at Teachers College, Columbia. Spending two years in the Army during
      his graduate training, his work was completed in 1958. He then joined the faculty
      of the Upstate Medical School of the State University of New York, Department of
      Psychiatry, moving on two years later to the Psychiatry Department at the
      University of Minnesota. In 1965 Sulzer moved to assume the directorship of the
      Behavior Modification Program, in the Rehabilitation Institute at Southern
      Illinois University, where he remained until his death on February 28, 1970.In
      observance of the 10th anniversary of the death of Edward Stanton Sulzer, these
      reminiscences are presented. They describe how an individual psychologist could
      affect the professional and personal lives of many. Edward Sulzer is described in
      terms of the environment that shaped his values, how they affected the actions of
      his students and clients, and how they are reflected in current social policy.
      The account leads to a conclusion that the actions of single individuals may
      influence the course of human events.

PMID- 22478536
TI  - Current measurement in applied behavior analysis.
AB  - The analysis of behavior began with a form of data, rate of responding, which
      allowed for efficient study and for the description of the basic principles of
      behavior. Especially important were the facts that rate of responding was a
      direct reflection of fundamental properties of behavior, and that rate of
      responding was measured continuously within an experimental session. As behavior
      analysts moved from purely experimental to applied settings, discontinuous, time
      based methods of measurement evolved, which neither directly reflect fundamental
      properties of behavior nor continuously record behavior within an experimental
      session. This paper offers a critical discussion of current measurement
      practices, and discusses factors possibly related to the use of discontinuous,
      time-based observing/recording procedures. A theoretical basis for
      observing/recording procedures is presented which emphasizes continuous
      measurement of response dimensions directly related to fundamental properties of
      behavior.

PMID- 22478537
TI  - The spread of behavior analysis to the applied fields.
AB  - This paper reviews the status of applied behavioral science as it exists in the
      various behavioral fields and considers the role of the Association for Behavior
      Analysis in serving those fields. The confounding effects of the traditions of
      psychology are discussed. Relevant issues are exemplified in the fields of law,
      communications, psychology, and education, but broader generalization is implied.

PMID- 22478538
TI  - On pigeons and people: A preliminary look at the columban simulation project.
AB  - Simulations of complex human behaviors with pigeons are providing plausible
      environmental accounts of such behaviors, as well as data-based commentaries on
      non-behavioristic psychology. Behaviors said to show "symbolic communication,"
      "insight," "self-awareness," and the "spontaneous use of memoranda" have thus far
      been simulated, and other simulations are in progress.

PMID- 22478539
TI  - A cogito-behavioro-summing up.

PMID- 22478540
TI  - Response cost: A case for specificity.

PMID- 22478541
TI  - The flight to the laboratory.

PMID- 22478542
TI  - A flight of behavior analysis.

PMID- 22478543
TI  - The schism between experimental and applied behavior analysis: Is it real and who
      cares?
AB  - This paper addresses the relationship between the experimental analysis of
      behavior and applied behavior analysis. Citation data indicate that across time
      the Journal of the Experimental Analysis of Behavior, and other experimental
      sources, have been referenced increasingly infrequently in the Journal of Applied
      Behavior Analysis, Behavior Therapy, and Behavior Research and Therapy. Such
      sources are now rarely cited in these journals, and never have been regularly
      referenced in Behavior Modification. Although their proper interpretation is far
      from certain, these data partially support recent suggestions that the
      experimental analysis of behavior and applied behavior analysis are largely
      separate, insular fields. A questionnaire, mailed to the editorial staffs of the
      Journal of the Experimental Analysis of Behavior and the Journal of Applied
      Behavior Analysis, was intended to gather further information about the alleged
      schism between the fields. Few respondents regularly read both journals, publish
      in both journals, or find both journals useful in their current research efforts.
      The majority of editors of both journals indicated that the fields were growing
      apart, although there was no consensus that this is harmful for behavior
      analysis. Most editors of the Journal of Applied Behavior Analysis reported that
      research published in the Journal of the Experimental Analysis of Behavior has
      decreased in value to applied researchers across time; most editors of the
      Journal of the Experimental Analysis of Behavior indicated that research
      published there has not changed in applied value. Several respondents commented
      at length concerning the relationship of experimental and applied behavior
      analysis. These comments, many of which appear in the article, reveal a marked
      plurality of views.

PMID- 22478544
TI  - Behavior analysis in instructional design: A functional typology of verbal tasks.
AB  - This paper describes and illustrates a typology of verbal instructional tasks for
      advanced classroom instruction and inservice training. The typology is based upon
      functional definitions of elementary and conceptual behavior, and incorporates
      the kinds of goals and objectives that surveys and research have shown to be
      important for experienced learners. The typology's metastructure is B. F.
      Skinner's (1957) verbal behavior classification system. This paper describes
      Skinner's system as a context for understanding and selecting instructional tasks
      for experienced learners. This paper also discusses rate of response as an
      important dimension of proficiency or mastery, and procedures for selecting
      proficiency criteria of tasks in the typology are also described. Results of the
      first of a series of validation studies indicated that high agreement between
      typology designer and subjects' classification of tasks can be attained after a
      short training session. The typology is discussed as a vehicle for standardizing
      instructional research and practice, and as a basis for research on transfer of
      control across classes of verbal behavior. Implications for research on building
      fluency of adult performance, and efficiency in instructional design are also
      discussed.

PMID- 22478545
TI  - Overcorrection: A review and critical analysis.
AB  - This paper reviews the overcorrection literature with a focus on the subject
      populations, dependent variables, procedural variations and research methodology
      reflected in overcorrection research. It analyzes overcorrection in terms of its
      punishment characteristics, and based on this, offers suggestions for the
      effective use of overcorrection. It raises issues regarding generalization and
      maintenance and the lack of data supporting claims for an educative value of
      overcorrection. We conclude that overcorrection can be an effective response
      suppressing procedure with greater social acceptability than other forms of
      punishment, but that the staff time involved in its use constitutes a possible
      drawback. We suggest the need for analytic research to identify overcorrection's
      critical components and minimal effective duration. Finally, we offer a
      suggestion for the use of more descriptive and precise terminology with respect
      to overcorrection procedures.

PMID- 22478547
TI  - A cogito-behavioro-summing up.

PMID- 22478546
TI  - Describing response-event relations: Babel revisited.
AB  - The terms used to describe the relations among the three components of
      contingencies of reinforcement and punishment include many with multiple meanings
      and imprecise denotation. In particular, usage of the term "contingency" and its
      variants and acceptance of unsubstantiated functional, rather than procedural,
      descriptions of response-event relations are especially troublesome in the
      behavior analysis literature. Clarity seems best served by restricting the term
      "contingency" to its generic usage and by utilizing procedural descriptions of
      response-event relations.

PMID- 22478548
TI  - Charles B. Ferster 1922-1981.

PMID- 22478550
TI  - Concerning Michael's concerns.

PMID- 22478549
TI  - On behavioral analysis.

PMID- 22478551
TI  - The spread of behavior analysis to social work.

PMID- 22478552
TI  - Contrived reinforcement.

PMID- 22478553
TI  - Can linguistics contribute to the study of verbal behavior?
AB  - A number of publications during the last decade reveal a growing interest in
      linguistics and psycholinguistics among some radical behaviorists, who have
      proposed a direct rapprochement between a formal analysis of language and a
      functional account. It is argued that whereas function has to do with the
      circumstances under which verbal behavior is emitted, structure has to do with
      its "internal organization," the ways in which sentences or parts thereof are
      presumably interrelated. These are said to be different dimensions of verbal
      behavior; together they should lead toward a coherent psychology of language. But
      psychologists bent on incorporating techniques from linguistics should be aware
      of its underlying assumptions, lest their work be deflected in essentially
      unproductive directions. The line between rapprochement and subservience is thin
      indeed, as the extant literature shows. This paper traces the development of
      mainstream contemporary psycholinguistics and examines the linguist's assumptions
      about the subject matter in the light of a behavioral analysis. The possibility
      of an effective reconciliation seems to be a long way off.

PMID- 22478554
TI  - The basic-applied continuum and the possible evolution of human operant social
      and verbal research.
AB  - Human operant research is typically viewed as fitting somewhere between the end
      points of a basic-to-applied continuum. Viewed in this way, the major role of
      human operant research is to determine the conditions under which principles
      discovered with animals also hold with humans. Relative to the basic and applied
      end points, which have defined the major journals and graduate training programs
      in Behavior Analysis, the human operant area has not been strong since the late
      1950's when a scientifically based application was only an exciting possibility.
      However, application quickly became a reality and to some extent it replaced the
      major role of human operant research. After about 15 years of focusing on the
      basic and applied end points, an increasing number of behavior analysts are
      concerned about the large content of psychology (e.g., social and verbal
      behavior) between the end points and the continued growth of Behavior Analysis.
      Basic research in social and verbal behavior should ordinarily begin with the
      human instead of a lower animal, because the human is the most qualified and
      prepared subject in the sense that most complex social and verbal behaviors are
      more accessible in humans. This new role for basic human research of initiating
      rather than only replicating, could result in a rebuilding of the "bridge"
      between basic and applied, and contribute to the growth of Behavior Analysis in
      terms of extensions to new content areas, methods, and the followers it would
      reach in these areas.

PMID- 22478555
TI  - From innovation to standard practice: developing and disseminating behavioral
      procedures.
AB  - This paper proposes a three-stage continuum for discussing the development and
      dissemination of behavioral technology. At the level of behavioral techniques,
      researchers need only establish a functional relationship between technologically
      defined intervention procedures and socially significant target behaviors.
      Dissemination is conducted for informational purposes only, and the purposes and
      details surrounding subsequent use of the technique are left to the discretion of
      the user. At the level of behavioral demonstration, a collection of socially
      acceptable intervention procedures is refined and standardized and must be shown
      to produce behavior changes across a number of subjects. Here dissemination is
      conducted, in large part, to generate support for provision of services. At the
      level of behavioral models, procedural descriptions must be useroriented.
      Additionally, model effects must be obtainable by agents not associated with
      their development and must compare favorably with other treatment or service
      alternatives. The purpose of dissemination at this level is to obtain adoptions
      and replications of the model. Details of development and dissemination of
      behavioral technology at each of these three levels are discussed.

PMID- 22478556
TI  - Graphics for three-term contingencies.
AB  - A source of confusion in the general readership regarding the relationship of
      operant to S-R psychology is traced to the use of graphics in the behavioral
      literature. A case is made for supplementing traditional linear notation systems
      with triangular graphics to illustrate three-term contingencies. Constructing
      discriminative stimuli in this fashion makes the distinction between operant and
      S-R formulations more conspicuous and reveals more comprehensive relationships
      for an extended radical behaviorism.

PMID- 22478557
TI  - Defining applied behavior analysis: an historical analogy.
AB  - This article examines two criteria for a definition of applied behavior analysis.
      The criteria are derived from a 19th century attempt to establish medicine as a
      scientific field. The first criterion, experimental determinism, specifies the
      methodological boundaries of an experimental science. The second criterion,
      philosophic doubt, clarifies the tentative nature of facts and theories derived
      from those facts. Practices which will advance the science of behavior are
      commented upon within each criteria. To conclude, the problems of a 19th century
      form of empiricism in medicine are related to current practices in applied
      behavior analysis.

PMID- 22478558
TI  - Countercontrols for the american educational research association.
AB  - Publications of the American Educational Research Association (AERA) maintain
      that years of research in education have failed to produce a useful technology
      for teachers. Little is said to be known about teaching children beyond the
      potential of new findings such as mastery learning, time on task, and features of
      an appropriate school climate. These latter conclusions are in stark contrast to
      the large body of useful findings in the behavior analysis literature. Several
      possible reasons are discussed for the discrepancy in views between behavior
      analysts and educational researchers. The lack of acknowledgement of behavior
      analysis is viewed as a serious problem because of the control that the
      educational research establishment exerts over federal funding of research and
      the training of teachers. There is a growing use of some of the aspects of
      behavior analysis by educational researchers; however, the derivation is not
      acknowledged and there is little enlightenment about radical behaviorism. It is
      suggested that ABA should countercontrol the influence of AERA by incorporating
      doctoral students in educational research as students of behavior analysis,
      teaching the complexity of behaviorism, teaching the positions of the opposing
      camp to behavior analysis students. ABA can take an aggressive role in
      countercontrolling AERA by forming committees to insure (a) quality of treatment,
      (b) funding representation in government, (c) protection and qualified review of
      untenured behavior analysts, (d) expansion of certification.

PMID- 22478559
TI  - The acquisition and maintenance of behavioral skills: a response to Michael.
AB  - A response to Michael's (1980) presidential address to the Association for
      Behavior Analysis is presented. The position is taken that in many instances we
      have failed to adopt a behavioral approach to dealing with problems within our
      field concomitant with the shift from an emphasis on behaviorism and a science of
      behavior to technology. It is argued that we need to be sensitive to the data and
      consider the contingencies that are operating within the culture. A general
      strategy and some tactics are presented to acquire and maintain behavioral
      skills.

PMID- 22478560
TI  - Feedback is not a new principle of behavior.

PMID- 22478561
TI  - Comments on Baer's "A flight of behavior analysis".

PMID- 22478563
TI  - Comments on cognitive science in the experimental analysis of behavior.
AB  - Arguments are increasingly being made for the inclusion of cognitive science in
      the experimental analysis of behavior (TEAB). These arguments are described, and
      a critical analysis of them is presented, especially in regards to the logic of
      objective inference and the renewed use of cognitive intervening variables. In
      addition, one particular defining feature of cognitive processes (i.e., the
      absence of an immediate controlling stimulus) is described, along with
      alternative points of view stressing molar-molecular levels of analysis and
      historical causation. Finally, comments are made on the use of cognitive concepts
      and language in the behavioral sciences. On all of these issues, counter
      arguments are based on available material in behavior analysis metatheory,
      concepts, and experimental practices.

PMID- 22478564
TI  - The fixed-interval scallop in human affairs.
AB  - "Fixed-interval scalloping" is used to describe certain everyday patterns of
      behavior in textbooks and other educational communications. This is a misleading
      use of the term. It implies that the behavior is accounted for by the schedule,
      when, in fact, many other variables are operating. This paper reviews eleven such
      variables and the research evidence on them. These variables provide a more
      adequate account of complex behavior and point up areas of limited knowledge
      requiring further research in both laboratory and applied settings. Extrapolating
      from basic research on human fixed-performance suggests that there are phenomena
      of mutual interest to both basic and applied behavior analysts.

PMID- 22478565
TI  - The analysis of human operant behavior: A brief census of the literature: 1958
      1981.
AB  - A census involving several major journals was conducted to survey the content and
      scope of the experimental analysis of human behavior. While the percentage of
      reports involving human subjects published each year in JEAB has lacked
      consistency, it was shown that JEAB has been the primary outlet for human work
      among the journals surveyed. Few areas of interest within the study of human
      behavior have received extensive scrutiny. The normal adult (typically
      undergraduate students) has been the preferred subject for human research. The
      results of a citation analysis of JEAB reports featuring human research are also
      presented.

PMID- 22478566
TI  - The place of the human subject in the operant laboratory.
AB  - Although laboratory study of human behavior seems an obvious vehicle for
      strengthening the scientific base of behavior analysis, the place of the human
      subject within the operant laboratory remains problematic. The prevailing
      research strategy has been to link principles developed with animals to human
      affairs, either through interpretation of naturally occurring human behaviors or
      through application of the principles to the solution of human problems. The
      paucity of laboratory research on human operant behavior derives from several
      misconceptions: the possibility that experimental demand characteristics and pre
      experimental behavioral dispositions of human subjects contaminate the results;
      that ethical considerations place undue constraint on research topics and
      experimental designs; and that uncontrollable variation in subjects' histories
      and other relevant personal characteristics prevents observation of reliable
      functional relations. We argue that these problems do not pose insurmountable
      obstacles to the experimental analysis of human behavior; that adequate methods
      of control and analysis are available; and that operant techniques, by
      emphasizing experimentally imposed contingencies, are well suited for the
      laboratory study of human behavior.

PMID- 22478567
TI  - The influence of Kantor's interbehavioral psychology on behavior analysis.
AB  - The contributions of J. R. Kantor and his system of interbehavioral psychology to
      the field of behavior analysis are examined. Two sources of information served to
      organize this investigation: (1) the historical record as described in the
      literature and (2) the results of a questionnaire survey sent to past and present
      editorial board members of the Journal for the Experimental Analysis of Behavior,
      the Journal of Applied Behavior Analysis, and Behaviorism. The outcome of this
      investigation showed that Kantor has had a broader influence than might
      heretofore have been recognized. More importantly, contemporary behavior analytic
      research and theory are evolving in directions either influenced by, or consonant
      with, his approach. We conclude that Kantor's interbehavioral psychology and his
      writings offer an important and valuable source of ideas and concepts for the
      future of behavior analysis.

PMID- 22478568
TI  - Concurrent behavior: are the interpretations mutually exclusive?
AB  - The experimental literature is replete with examples of behavior which occur
      concurrently with a schedule of reinforcement. These concurrent behaviors, often
      with similar topographies and occurring under like circumstances, may be
      interpreted as functionally autonomous, collateral, adjunctive, superstitious or
      mediating behavior. The degree to which the interaction of concurrent and
      schedule controlled behavior is used in the interpretation of behavior
      illustrated the importance of distinguishing among these interpretations by
      experimental procedure. The present paper reviews the characteristics of these
      interpretations, and discusses the experimental procedures necessary to
      distinguish among them. The paper concludes that the interpretations are mutually
      exclusive and refer to distinct behaviors, but that the distinction between any
      two of the interpretations requires more than one experimental procedure.

PMID- 22478569
TI  - Subjects used in JEAB articles: is the snark a pigeon?

PMID- 22478570
TI  - Determinism.

PMID- 22478571
TI  - The importance of analysis in behavioral technology: a response to Paine and
      Bellamy.

PMID- 22478572
TI  - Can the experimental analysis of behavior rescue psychology?

PMID- 22478573
TI  - Nurturing behavioral repertoires within a nonsupportive environment.
AB  - Recent articles have expressed concern over the increasing retreat to mentalism
      among behaviorists. The problem has been described elsewhere as a shift in verbal
      behavior resulting from the contingencies imposed by mentalistic verbal
      communities. Previous solutions have focused on strengthening our behavioral
      graduate programs to make the graduates' verbal repertoires more resistant to
      change. We suggest it is useful to analyze the problem in terms of inappropriate
      audience control and offer an approach by which behaviorists may assemble
      audiences to maintain their behavioral verbal repertoires within mentalistic
      verbal communities.

PMID- 22478574
TI  - Applied behavior analysis: New directions from the laboratory.
AB  - Applied behavior analysis began when laboratory based principles were extended to
      humans inorder to change socially significant behavior. Recent laboratory
      findings may have applied relevance; however, the majority of basic researchers
      have not clearly communicated the practical implications of their work. The
      present paper samples some of the new findings and attempts to demonstrate their
      applied importance. Schedule-induced behavior which occurs as a by-product of
      contingencies of reinforcement is discussed. Possible difficulties in treatment
      and management of induced behaviors are considered. Next, the correlation-based
      law of effect and the implications of relative reinforcement are explored in
      terms of applied examples. Relative rate of reinforcement is then extended to the
      literature dealing with concurrent operants. Concurrent operant models may
      describe human behavior of applied importance, and several techniques for
      modification of problem behavior are suggested. As a final concern, the paper
      discusses several new paradigms. While the practical importance of these models
      is not clear at the moment, it may be that new practical advantages will soon
      arise. Thus, it is argued that basic research continues to be of theoretical and
      practical importance to applied behavior analysis.

PMID- 22478575
TI  - Subject selection in applied behavior analysis.
AB  - Past researchers have commented on the role of specifying relevant subject
      characteristics in determining the generality of experimental findings. Knowledge
      of subject selection criteria is important in interpreting and replicating
      research results. Such knowledge, as compared with many other historical and
      demographic characteristics of the subject, is likely to be related to a
      procedure's effectiveness. Data indicated that the majority of articles published
      in the Journal of Applied Behavior Analysis do not provide an adequate
      description of subject selection criteria. The failure to provide detailed
      information concerning subject selection criteria can prevent systematic
      replication of research results. The relatively low cost inclusion of complete
      descriptions of subject selection criteria would enhance the generality of
      applied behavior analysis research by facilitating systematic inductive
      manipulations and replications.

PMID- 22478576
TI  - Maladaptive functional relations in client verbal behavior.
AB  - Skinner's analysis of verbal behavior is applied in this paper to several kinds
      of maladaptive behavior with which clinicians must deal. Lying, denial, and poor
      observing skills are discussed as defective tacting repertoires. Demanding and
      manipulative behaviors are mands that obtain immediate reinforcement at the
      expense of disrupting long-term interpersonal relations. Obsessing is runaway
      intraverbal behavior. Variables that enter into the maladaptive functional
      relations are examined.

PMID- 22478577
TI  - Choice, matching, and human behavior: A review of the literature.
AB  - This review concerns human performance on concurrent schedules of reinforcement.
      Studies indicate that humans match relative behavior to relative rate of
      reinforcement. Herrnstein's proportional matching equation describes human
      performance but most studies do not evaluate the equation at the individual
      level. Baum's generalized matching equation has received strong support with
      humans as subjects. This equation permits the investigation of sources of
      deviation from ideal matching and a few studies have suggested variables which
      control such deviations in humans. While problems with instructional control are
      raised, the overall findings support the matching law as a principle of human
      choice.

PMID- 22478578
TI  - Two correct definitions of "Applied".

PMID- 22478579
TI  - Interspecies generality and human behavior: An addendum to Baron and Perone.

PMID- 22478580
TI  - Las Vegas knows better.

PMID- 22478581
TI  - Comments on Marr's determinism.

PMID- 22478582
TI  - Toward a science of history.
AB  - The scientific status of History was compared to other sciences in the critical
      areas event selection, investigative operations, and theory construction. First,
      in terms of events studied, history is regarded as a quasi-scientific study of
      past events. However, viewed from the science of behavior's perspective of what
      historians actually do, history becomes a study of current records. As a study of
      currently existing records, not the non-existent past, history has potential to
      become a science. Second, like other scientists, historians may undertake
      manipulative investigations: they can locate the presence and absence of a
      condition in records and thereby determine its relation to other recorded
      phenomena. A limitation has been the lack of quantification that results from
      emphasis on the uniqueness of things rather than on their communality. Scientific
      training would facilitate viewing similar things as instances of a larger class
      that could be counted. Another limitation that cannot be easily overcome is the
      inability to produce raw data. This limitation has created problems in
      theoretical practices, the third area of comparison, because theoretical
      constructions have frequently been substituted for missing data. This problem too
      could be reduced through scientific training, particularly in other behavior
      sciences. An authentic science of history is possible.

PMID- 22478583
TI  - A verbal behavior analysis of auditory hallucinations.
AB  - A review of recent research on the non-medical control of auditory hallucinations
      is presented. It is suggested that the decreases in hallucinatory behavior
      obtained in studies using aversive contingencies may be attributable to the
      disruption of the chains of behavior involved. The results of several additional
      studies are interpreted as indicating that methods of stimulus control and the
      use of incompatible behaviors may be effective in reducing the rate of auditory
      hallucinations. Research relating auditory hallucinations to subvocalizations is
      presented in support of the view that hallucinatory phenomena are sometimes
      related to the subject's own vocal productions. Skinner's views (1934, 1936,
      1953, 1957, 1980) are then presented as possible explanations of some
      hallucinatory behavior. It is suggested that some auditory hallucinations consit
      of the mishearing of environmental and physiological stimuli as voices in a
      fashion similar to that which Skinner observed in his work with the verbal
      summator. The maintenance of long chains of such responses may be largely
      attributable to self-intraverbal influences (such as are present during automatic
      writing). With some auditory hallucinations, this progression involves first
      mishearing ambiguous stimuli as voices and then attributing the voices to some
      cause (e.g., insanity, the television, radio, or God). Later, the frequent and
      ongoing chains of such behavior may contaminate other verbal responses. Such
      verbal behavior may be parasitic on "normal verbal behavior" (and hence, not
      directly dependent on consquences for maintenance), may be cued by various
      stimuli (including respiration), and may interfere with other covert and overt
      behavior. Several studies to investigate this view are presented. It is hoped
      that such research will lead to a better understanding of the major issues
      involved in the etiology and treatment of auditory hallucinations in particular
      and perhaps of psychosis in general.

PMID- 22478584
TI  - Participation by women in behavior analysis.
AB  - The participation of women in behavior analysis as authors of articles published
      in the Journal of the Experimental Analysis of Behavior (JEAB) and the Journal of
      Applied Behavior Analysis (JABA), as members of the Association for Behavior
      Analysis (ABA), and as contributors to the 1982 ABA convention was examined.
      Since the inception of JEAB and JABA, men have appeared as authors far more
      frequently than women, although women have published relatively more frequently
      in the latter journal than in the former. Across years, there has been an upward
      trend in the proportion of JEAB authors who are female; this is not the case for
      all JABA authors, although it does hold for senior authors. In 1980-1981 and 1981
      1982, females represented approximately half of ABA's student and affiliate
      members but less than a third of its full members. Approximately a third of the
      contributors to posters and symposia and a seventh of those delivering invited
      addresses at the 1982 ABA convention were women.

PMID- 22478585
TI  - Misconception and miseducation: Presentations of radical behaviorism in
      psychology textbooks.
AB  - Behavior analysts have recently expressed concern about what appear to be
      misrepresentations of behaviorism in psychology textbooks. This paper presents an
      analysis of currently used textbooks in the areas of introductory, social,
      cognitive, personality, and developmental psychology that confirms this. Topics
      on which behavior analysis is most often misrepresented relate to the role of
      animal learning research, environmentalism, the "empty organism," language, and
      the overall utility of the approach. Because textbooks are often a major medium
      of interaction between the public and behaviorism, behavior analysts must work to
      correct these errors and to prevent possible negative consequences of widespread
      misunderstanding. Several potential solutions to these problems are presented
      that take into account current publishing practices and the monetary
      contingencies which support them.

PMID- 22478587
TI  - An index to B. F. Skinner's particulars of my life.

PMID- 22478586
TI  - Twenty-five years of JEAB: A survey of selected demographic characteristics
      related to publication trends.
AB  - Some demographic characteristics related to authorship of research reports in the
      Journal of the Experimental Analysis of Behavior (JEAB) were analyzed as to
      affiliation and location (U.S. or foreign) of authors. In addition, the incidence
      of publications by the members of the editorial board was tallied. The number of
      different affiliations of JEAB authors has decreased steadily over the past
      several years with substantially fewer papers deriving from independent
      laboratories and medical schools. While the number of papers by foreign authors
      has generally increased over the years there is a recent reduction in their
      number. These data paint a mixed picture of the "health" status of the
      experimental analysis of behavior as reflected in its major publication outlet.

PMID- 22478588
TI  - When we speak of knowing.

PMID- 22478589
TI  - A reply to Vaughan.

PMID- 22478590
TI  - On mentalistic terms: Another view.

PMID- 22478591
TI  - Children are human too.

PMID- 22478592
TI  - On privacy, causes, and contingencies.
AB  - Radical behaviorism may be distinguished from other varieties of behaviorism,
      notably methodological behaviorism, by the way it accommodates private events in
      causal explanations of behavior. That is, in an operational sense, radical
      behaviorism accommodates private phenomena in the context of the three term
      contingency of reinforcement with regard to their discriminative function, their
      nature as responses, or their reinforcing function. In any case, any contribution
      of a private phenomenon is presumably linked at some point to a prior public
      event that has endowed the private phenomenon with its functional significance.

PMID- 22478593
TI  - Belief, its inconsistency, and the implications for the teaching faculty.
AB  - The traditional concept of belief is analyzed and compared with a behavior
      analytic concept of belief. Beliefs and belief statements are differentiated and
      relationships between them are examined. The often troublesome inconsistencies in
      people's beliefs are examined in general and explained, including the phenomena
      of compartmentalization and repression. Social implications are pursued relative
      to both punishment for inconsistency in belief and counter-controls thwarting
      such punishment. The role of teachers in shaping beliefs is analyzed, and
      appropriate teaching strategies are reviewed.

PMID- 22478594
TI  - Listening and understanding.
AB  - The activities involved in mediating reinforcement for a speaker's behavior
      constitute only one phase of a listener's reaction to verbal stimulation. Other
      phases include listening and understanding what a speaker has said. It is argued
      that the relative subtlety of these activities is reason for their careful
      scrutiny, not their complete neglect. Listening is conceptualized as a functional
      relation obtaining between the responding of an organism and the stimulating of
      an object. A current instance of listening is regarded as a point in the
      evolution of similar instances, whereby one's history of perceptual activity may
      be regarded as existing in one's current interbehavior. Understanding reactions
      are similarly analyzed; however, they are considerably more complex than
      listening reactions due to the preponderance of implicit responding involved in
      reactions of this type. Implicit responding occurs by way of substitute
      stimulation, and an analysis of the serviceability of verbal stimuli in this
      regard is made. Understanding is conceptualized as seeing, hearing, or otherwise
      reacting to actual things in the presence of their "names" alone. The value of an
      inferential analysis of listening and understanding is also discussed, with the
      conclusion that unless some attempt is made to elaborate on the nature and
      operation of these activities, the more apparent reinforcement mediational
      activities of a listener are merely asserted without an explanation for their
      occurrence.

PMID- 22478596
TI  - An index to B. F. Skinner's the shaping of a behaviorist.

PMID- 22478595
TI  - On "Setting events" and related concepts.
AB  - The term "setting event" is examined in light of recent interest in the possible
      utility of the concept. The term was found to characteristically include
      properties of environmental variables, functional relations already defined, and
      other functional relations either unspecified or not identified with any
      generally-accepted term. "Setting event" as a technical term may be too general
      and functionally unclear and should thus be viewed with caution. An alternative
      approach is examined in the recently-proposed term, "establishing operation,"
      which is viewed as a more limited, functionally specific, and therefore
      preferable approach to the adoption of new technical terms.

PMID- 22478597
TI  - A new term and some old advice.

PMID- 22478598
TI  - Reaction to Willems and McIntire's review of "Preserving the environment: New
      strategies for behavior change".

PMID- 22478599
TI  - Can radical behaviorism rescue psychology?

PMID- 22478600
TI  - A science of history.

PMID- 22478601
TI  - Participation by women in behavior analysis: Some recent data on authorship of
      manuscripts submitted to the journal of applied behavior analysis.

PMID- 22478602
TI  - Observational learning from a radical-behavioristic viewpoint.
AB  - Bandura (1972, 1977b) has argued that observational learning has some distinctive
      features that set it apart from the operant paradigm: (1) acquisition simply
      through observation, (2) delayed performance through cognitive mediation, and (3)
      vicarious reinforcement. The present paper first redefines those three features
      at the descriptive level, and then adopts a radical-behavioristic viewpoint to
      show how those redefined distinctive features can be explained and tested
      experimentally. Finally, the origin of observational learning is discussed in
      terms of recent data of neonatal imitation. The present analysis offers a
      consistent theoretical and practical understanding of observational learning from
      a radical-behavioristic viewpoint.

PMID- 22478603
TI  - Can a statement in cognitive terms be a behavior-analytic interpretation?

PMID- 22478604
TI  - The case for praxics.
AB  - Since the early 1900s a variety of names has been proposed for the scientific
      study of behavior, but none has come into general use. "Praxics," a recent entry,
      is defensible on several grounds. "Behaviorism," on the other hand, is the name
      of a school of philosophy. Though praxics has roots in behaviorism, the term
      "behaviorism" should not be applied to praxics. Confusion between the science and
      the philosophy has retarded the growth of the science immeasurably. Its growth
      has also been impeded by its association with psychology, which is still
      primarily the study of mind. Efforts are underway to establish praxics as an
      independent field.

PMID- 22478605
TI  - Contingency management in the people's republic of China.
AB  - The behavioral contingencies that have been implemented in the attempt by the
      People's Republic of China to achieve two of its national goals are described.
      The goals are the modernization and increased productivity of industry and a
      significant decrease in the birth rate. Changes from past practices in the
      industrial sphere involving a shift from noncontingent to contingent consequences
      are outlined. The use of a variety of consequences as a means of reducing the
      birth rate is described.

PMID- 22478606
TI  - Teachers and students: Reflections on social control and future performance.
AB  - To instruct consists of arranging controls between teacher, student, and subject
      matter. Initial controls must emanate from the teacher since those of the subject
      matter are minimal, crude, or missing. Teachers mand students to behave in
      certain ways with respect to a given subject matter. Eventually, however, the
      teacher must transfer the teacher mediated and managed control of the student to
      natural controls functioning directly through student interaction with the
      subject matter. Difficulty in doing this occurs due to the reinforcers for both
      student and teacher derived from social contact. Nevertheless, the student
      eventually must be taught to interact with the subject matter independent of
      teacher involvement if the student is to maintain effective contact with the
      subject matter beyond the period of formal instruction.

PMID- 22478607
TI  - Toward a functional analysis of delusional speech and hallucinatory behavior.
AB  - An approach to a functional analysis of delusional speech and hallucinatory
      behavior is described and discussed using concepts found in Goldiamond's (1975a
      and 1984) nonlinear contingency analysis and Skinner's Verbal Behavior (1957).
      This synthesis draws upon and concords with research from the animal laboratory,
      with the extensive experimental literatures on stimulus control and signal
      detection theory, and with our own clinical experiences.In this formulation,
      delusional speech and hallucinatory behavior are viewed as successful operants.
      Accordingly, we argue that such behaviors can be considered adaptive and
      rational, rather than maladaptive and irrational, when analyzed within a model of
      consequential governance that includes alternative sets of contingencies. Several
      clinical examples are offered to illustrate both analytic procedures and the
      design of systemic treatment programs based upon a behavioral contingency
      analysis derived from a natural science of behavior. Throughout, we emphasize the
      consequential governance of these clinically important classes of behavior, in
      contrast to other approaches which suggest formal similarities to operant verbal
      behavior but largely ignore the role of consequential contingencies.

PMID- 22478609
TI  - J. R. Kantor's contributions to psychology and philosophy: A guide to further
      study.

PMID- 22478608
TI  - A citation analysis of the influence on research of Skinner's verbal behavior.
AB  - The influence of Skinner's Verbal Behavior on the generation of verbal behavior
      research was examined in a citation analysis that counted the citations of the
      book from January 1957 to August 1983 and described the fields in which the
      citations occurred. In a subsequent content analysis, citations were classified
      as directly influenced by the book if they selected at least one of Skinner's
      classes of verbal behavior for empirical examination. Directly influenced
      citations were sorted as descriptive, applied, or basic. The total number of
      citations of the book (836), the increasing annual number of citations, and the
      range of fields in which the book has been cited are evidence of its broad
      influence. However, empirical investigations employing at least one of Skinner's
      classes of verbal behavior are only a small proportion (31/836) of the citations.
      Of this small proportion an even smaller number constitutes experimental analyses
      (19/836). The small proportion of empirical studies suggests that Verbal Behavior
      is primarily cited for reasons other than as source material for research
      hypotheses in the study of verbal behavior. Some speculations are offered to
      account for the book's limited influence on research.

PMID- 22478610
TI  - Conceptual contributions of Kantor's interbehavioral psychology.
AB  - Kantor's interbehavioral psychology may be characterized by its conceptual
      emphases upon (a) naturalism, (b) scientific pluralism, (c) organism-environment
      interactions, and (d) integrated event fields of continuously interrelated and
      interrelating factors. Despite differences between Skinnerian and Kantorian
      classification schemes, the conceptual features of interbehaviorism are
      compatible with those of Skinner's behaviorism, and taken together the two
      provide a firm theoretical foundation for an authenticially behavioristic
      psychology.

PMID- 22478611
TI  - Some reflections on Kantor's (1970) "An analysis of the experimental analysis of
      behavior (TEAB)".

PMID- 22478612
TI  - Interbehavioral psychology and radical behaviorism: Some similarities and
      differences.
AB  - Both J. R. Kantor's interbehavioral psychology and B. F. Skinner's radical
      behaviorism represent wellarticulated approaches to a natural science of
      behavior. As such, they share a number of similar features, yet they also differ
      on a number of dimensions. Some of these similarities and differences are
      examined by describing their emergence in the professional literature and by
      comparing the respective units of analysis of the two approaches-the
      interbehavioral field and the three-term contingency. An evaluation of the
      similarities and differences shows the similarities to be largely fundamental,
      and the differences largely ones of emphasis. Nonetheless, the two approaches do
      make unique contributions to a natural science of behavior, the integration of
      which can facilitate the development of that science and its acceptance among
      other sciences and within society at large.

PMID- 22478613
TI  - Comparing humans to other species: We're animals and they're not infrahumans.

PMID- 22478614
TI  - The complex case of Brownstein and Shull's review of Schwartz and Lacey.

PMID- 22478615
TI  - Reasoning about hallucinations.

PMID- 22478616
TI  - News from nowhere, 1984.

PMID- 22478617
TI  - Some reciprocal roles between behavior analysis and institutional economics in
      post-darwinian science.
AB  - Behavior analysis and institutional economics are viewed as having common origins
      in the early 20th century effort to benefit from the conceptual revolution
      spurred by Darwin's synthesis. Institutional economics, initiated by Thorstein
      Veblen, appears to have failed to develop a progressive scientific technology,
      while behavior analysis has done so. It is suggested that institutional economics
      has been held back by lack of a synthesizing scientific mechanism that elucidates
      the relation between technological and ceremonial processes, the two cultural
      forces described by Veblen. The theory of institutional economist C. E. Ayres,
      built on Veblen's distinction, is used to clarify the concepts of technological
      and ceremonial processes for the reader. An analysis of the behavioral processes
      that might underlie the cultural processes described by Veblen/Ayres suggests
      that the experimental analysis of behavior has provided concepts that might
      function as a synthesizing mechanism for the social sciences and, in particular,
      institutional economics. The Veblen/Ayres dichotomy, now seen in terms of
      underlying behavioral processes, is used to examine the field of behavior
      analysis in terms of its origins, its relation to psychology and its current
      state. The paper concludes with a few practical suggestions as to how behavior
      analysts might work to enhance survival.

PMID- 22478618
TI  - A behaviorist's response to the report of the national commission on excellence
      in education.
AB  - The National Commission on Excellence in Education was charged with the
      responsibility for examining the quality of education in America. Its report, "A
      Nation at Risk" (1983), contained a set of alarming facts about the status of
      American education. These were followed by a set of five major recommendations
      for improving the situation. They related to (1) content, (2) standards and
      expectations, (3) time, (4) teaching, and (5) leadership and support. The present
      paper examines each of the set of recommendations from a behavior analytic
      perspective. It notes what the field of behavior analysis can say on the subject
      now; what it potentially might address and remediate at this time; what it might
      explore and predict; and in general what it can do to make a difference. Behavior
      analysis has made many important discoveries that should be communicated to
      educators and the public, and it has tools and concepts for further contributing
      toward the improvement of education.

PMID- 22478619
TI  - Adlerian psychology as an intuitive operant system.
AB  - Traditional accounts of the Individual Psychology of Alfred Adler tend to
      sentimentalize his system and obscure its functional flavor. Six basic Adlerian
      positions on human behavior, including Rudolf Dreikurs' "four goals of
      misbehavior," are interpreted as a primitive statement of operant principles.
      Applied techniques long used by Individual Psychology practitioners strongly
      resemble interventions that applied behavior analysts have developed by more
      systematic means.

PMID- 22478620
TI  - Some historical and conceptual relations among logical positivism, operationism,
      and behaviorism.
AB  - Historical and conceptual relations among logical positivism, conventional
      operationism, and behaviorism are examined from the standpoint of Skinner's
      radical behaviorism. Although logical positivism and conventional operationism
      sought the formulation and application of an epistemology based strictly upon
      physicalistic principles and experiential verification, the application of that
      epistemology in psychology has resulted in the perpetuation, rather than the
      resolution, of a number of mentalistic, if not outright dualistic, problems.

PMID- 22478621
TI  - Designing courseware: Prompts from behavioral instruction.
AB  - Behavior analysis has been at the forefront of instructional design for many
      years. However, this leadership position is rapidly eroding as teachers, trainers
      and other educators insist that behavioral instruction is good only for meeting
      simplistic educational goals. I argue that in order for behavior analysis to
      continue to influence the field of instructional design, behavior analysts need
      to help people develop instructional programs that use advanced interactive
      computer systems and that are based on all the components of behavioral
      instruction. Therefore, this paper suggests the following strategy. First, it
      teaches people to select authoring systems that will enable them to design
      interactive computer programs. Second, in order to improve current authoring
      systems it provides a set of prompts that integrate the features of behavioral
      instruction. I claim that the integration of these prompts with an advanced
      authoring system will facilitate the development of complex, conceptual learning
      programs and minimize current criticisms of behavioral instruction.

PMID- 22478622
TI  - Use of electrical shock in nonhuman research: A survey of JEAB studies.

PMID- 22478623
TI  - Public information, dissemination, and behavior analysis.
AB  - Behavior analysts have become increasingly concerned about inaccuracies and
      misconceptions in the public, educational, and professional information
      portraying their activities, but have done little to correct these views. The
      present paper has two purposes in this regard. First, the paper describes some of
      the conditions that have given rise to these concerns. Second, and more
      important, the paper surveys various procedures and programs for the
      dissemination of public information that may correct inaccuracies and
      misconceptions. Special consideration is also given to issues involving (a) the
      assessment of the problem, (b) the content and means of dissemination, (c) the
      possible contributions of behavior analysts to current misunderstandings, and (d)
      relationships between behavior analysts and the media. The dissemination of
      accurate and unbiased information constitutes an important new undertaking for
      behavior analysis. The future of the field may depend in part on such activity.

PMID- 22478624
TI  - A historical and pedagogic note on establishing operations.

PMID- 22478625
TI  - Praxics and behaviorism.

PMID- 22478626
TI  - Praxics and the case for radical behaviorism.

PMID- 22478627
TI  - The ABP contingency.

PMID- 22478628
TI  - The ABP noncontingency: A response to "The ABP contingency".

PMID- 22478629
TI  - A reply to Clark regarding auditory hallucinations.

PMID- 22478630
TI  - Behavior analysis, amelioration, and the control of human behavior.

PMID- 22478631
TI  - On differentiation in applied behavior analysis.
AB  - Distinct types of activity in the field of applied behavior analysis are noted
      and discussed. Four metaphorical types of activity are considered: prospecting,
      farming, building, and guiding. Prospecting consists of time-limited exploration
      of a variety of beaviors, populations, or settings. Farming consists of producing
      new behaviors in the same setting using independent variables provided by the
      researchers or normally available in the setting. Building consists of combining
      procedural elements to create new programs or systems or to rehabilitate aspects
      of existing programs. Guiding involves pointing out connections between the
      principles of human behavior and the problems, populations, settings, and
      procedures with which researchers are (or could be) working. Advantages of each
      sphere are noted, and benefits of this division of labor to the field as a whole
      are discussed.

PMID- 22478632
TI  - Behavior analysis and behavioral ecology: A synergistic coupling.
AB  - Recent trends in behavioral ecology and behavior analysis suggest that the two
      disciplines complement one another, underscoring the desirability of an
      integrated approach to behavior. Three examples from the foraging literature
      illustrate the potential value of an interdisciplinary approach. For example, a
      model of natural selection for foraging efficiency-optimal foraging theory-makes
      several predictions consistent with an hypothesis of a more proximate phenomenon,
      the reduction in delay to primary reinforcement. Not only are the ecological and
      behavior analytic approaches to behavior complementary, but each may provide
      insights into the operation of controlling variables in situations usually
      thought of as being the other's domain.

PMID- 22478633
TI  - Doctoral training in behavior analysis: Training generalized problem-solving
      skills.
AB  - This essay provides guidelines for designing a doctoral program in behavior
      analysis. First, we propose a general accomplishment for all behavior analytic
      doctoral students: that they be able to solve problems concerning individual
      behavior within a range of environments. Second, in order to achieve this goal,
      we propose that students be trained in conceptual and experimental analysis of
      behavior, the application of behavioral principles and the administration of
      behavioral programs. This training should include class work, but it should
      emphasize the immersion of students in a variety of environments in which they
      are required to use behavior analytic strategies. Third, we provide an example of
      a hypothetical graduate program that involves the proposed training. Finally, an
      evaluation plan is suggested for determining whether a training program is in
      fact producing students who are generalized problem-solvers. At each step, we
      justify our point of view from a perspective that combines principles from
      behavior analysis and educational systems design.

PMID- 22478634
TI  - Reflections on a cumulative record.

PMID- 22478635
TI  - On the impact of human operant research: Asymmetrical patterns of cross-citation
      between human and nonhuman research.
AB  - Reactions to published accounts of research with human subjects, as well as
      research with nonhuman subjects, were assessed by examining citations in several
      samples of empirical articles in the Journal of the Experimental Analysis of
      Behavior. A stable, asymmetrical pattern emerged: Nonhuman research was cited in
      both human and nonhuman articles, but human research was cited primarily in human
      articles. Thus, human operant research appears to have had little influence on
      the nonhuman research which constitutes the bulk of the experimental analysis of
      behavior. Interpretation of this lack of impact depends on the functions one
      envisions for human research, several of which are discussed.

PMID- 22478637
TI  - Calculating percentage agreement correctly but writing its formula incorrectly.

PMID- 22478636
TI  - Behavior analytic studies of creativity: A critical review.
AB  - Studies that treat creativity as operant behavior were critically reviewed. Of
      the twenty studies, most met minimal requirements for methodological adequacy;
      all provided at least some evidence for increased creative responding. Major
      difficulties involved potential confounds between instructions and contingencies,
      lack of an independent record of the training interaction, lack of social
      validation data, and very limited evidence for generalization. Several issues
      were discussed: problems in the behavioral definition of creativity, objections
      to the use of contingent reinforcement, and the need for empirical analysis of
      the creative process.

PMID- 22478638
TI  - An index to B. F. Skinner's a matter of consequences.

PMID- 22478639
TI  - Stimulus control terminology.

PMID- 22478640
TI  - A rule for the use of the term, "Rule-governed behavior".

PMID- 22478641
TI  - Further comments on praxics: Why the devotion to behaviorism?

PMID- 22478642
TI  - Courseware and behavioral instruction: The design and dissemination of effective
      teaching systems.

PMID- 22478643
TI  - On radicalizing behaviorism: A call for cultural analysis.
AB  - Our culture at large continues many practices that work against the well-being of
      its members and its chances for survival. Our discipline has failed to realize
      its potential for contributing to the understanding of these practices and to the
      generation of solutions. This failure of realization is in part a consequence of
      the general failure of behavior analysts to view social and cultural analysis as
      a fundamental component of radical behaviorism. This omission is related to three
      prevailing practices of our discipline. First, radical behaviorism is
      characteristically defined as a "philosophy of science," and its concerns are
      ordinarily restricted to certain epistemological issues. Second, theoretical
      extensions to social and cultural phenomena too often depend solely upon
      principles derived from the analysis of behavior. Third, little attention has
      been directed at examining the relationships that do, or that should, exist
      between our discipline and related sciences. These practices themselves are
      attributed to certain features of the history of our field. Two general remedies
      for this situation are suggested: first, that radical behaviorism be treated as a
      comprehensive world view in which epistemological, psychological, and cultural
      analyses constitute interdependent components; second, that principles derived
      from compatible social-science disciplines be incorporated into radical
      behaviorism.

PMID- 22478644
TI  - Toward a technology of generalization: The identification of natural
      contingencies of reinforcement.
AB  - Applied behavior analysts have directed a growing effort towards the development
      of a technology for behavioral generalization and maintenance over the past
      decade. Among the list of potential generalization promoters thought to exist is
      the natural contingency of social reinforcement (i.e., a behavioral trap) for new
      behavior in its untrained form or setting, or over time. Although past
      researchers have noted a need to program for the generalization and maintenance
      of behavior change, the current understanding of behavioral traps precludes the
      use of these contingencies to support behavioral changes when interventions are
      not in operation. This article describes five forms of evidence useful for the
      identification and analysis of natural contingencies of reinforcement. Examples
      from the applied research literature are provided to illustrate the kinds of
      studies that would greatly enhance our knowledge of behavioral traps and improve
      our ability to understand and program the generalization of trained behaviors
      across diverse forms and settings, and over time.

PMID- 22478645
TI  - Competition: Some behavioral issues.
AB  - Conclusions drawn from research in the social sciences comparing the quality or
      quantity of performance under cooperation and competiton stress the advantages of
      cooperation. This generalization may be premature, however, because of the
      paucity of experimental analyses investigating variations in competitive
      conditions. Neglected in particular have been variables that affect reinforcement
      conditions among competitors. These include performance differences, the basis of
      reinforcement, reinforcer distribution, and stimuli that indicate the
      performances of other competitors. These variables provide the basis for a
      behavioral interpretation of performance under competition. The result is a
      clearer understanding of the options that are available in instituting
      competitive contingencies and the areas in which experimental analyses are
      needed.

PMID- 22478646
TI  - Public policymaking and research information.
AB  - The public policymaking process presents behavior analysts with opportunities to
      shape public policy and influence decisions that affect the evolution of
      communities. Although the scientist-advocate's role in public policymaking has
      received increased attention, little attention has been given to behavioral
      analyses of the policymaking context. This paper describes the stages of
      policymaking, including agenda formation, policy adoption, policy implementation,
      and policy review. It also analyzes seven types of research information important
      in agenda formation and policy adoption-information about the dimensions of an
      issue, number of people affected, relative standing of an issue, interests of
      those involved, controlling variables, program alternatives, and program
      acceptability. Methods for communicating research information to policymakers are
      discussed.

PMID- 22478647
TI  - Separate disciplines: The study of behavior and the study of the psyche.
AB  - The study of behavior differs fundamentally from the study of the psyche and
      logically cannot share the same discipline. However, while disciplines might be
      defined through technical exercises, they function through exercises of political
      power. The evolution of a discipline, though based on field and laboratory data
      interpreted within a specific paradigm and justified publicity by its utility to
      solve personal and social problems, follows a course of development in the
      political arenas of the academies and the professions. We happen to have a
      discipline, roughly connoted by the label "behavior analysis," without an
      academic home (the present ones haphazardly tolerate our activities), without a
      professional organization (the present one lobbies only "for behavior analysis"),
      and without a true professional name (the present one implies an approach not a
      discipline). No scientific community lasts long without a supporting professional
      infrastructure. In explicitly asserting ourselves as a discipline, we confront a
      number of difficult issues such as continuing to work in departments antithetical
      to behaviorism and a number of problems such as what we call ourselves to
      identify our professional and scientific concerns. (For example, we need a term
      descriptive of our science in its broad sense. That term is not psychology. Too
      many people persist in maintaining its commitment to cognitivism. On whatever
      term we agree, "behavior" should constitute its stem, for our efforts focus
      there, not in the putative underlying psyche or its current cognitive update.)
      The focus of our concerns and the solutions of our problems rest on one issue:
      Will our discipline prosper most as a branch of psychology or as an independent
      discipline? Slowly, but surely, our actions demonstrate that the latter is the
      preferred option, but these actions, though fortuitous, occur almost by accident.
      By specifically programming to achieve an independent professional status we
      increase the probability of doing so.

PMID- 22478648
TI  - The threat of nuclear war: Some responses.
AB  - The possibility of nuclear holocaust threatens the very existence of the world
      community. Biologists, earth scientists, educators, lawyers, philosophers,
      physicists, physicians, and social scientists have addressed the problem from
      their special perspectives, and have had substantial impact on the public.
      Behavior analysts, however, have not as a whole contributed a great deal to the
      goal of preventing nuclear catastrophe. We argue that the threat of nuclear war
      is primarily a behavioral problem, and present an analysis of that problem. In
      addition, we address the difficulty of implementing behavioral interventions that
      would contribute to the survival of the World.

PMID- 22478649
TI  - The early research of John B. Watson: Before the behavioral revolution.
AB  - John B. Watson is widely regarded as one of the most important figures in modern
      psychology. Despite this stature, however, presentations of his contributions and
      career are usually limited to material on his establishment of classical
      behaviorism in 1913, and then on subsequent elaborations of his position and on
      his study of conditioned emotional reactions. Watson's career and research prior
      to 1913 are rarely mentioned or cited; moreover, when this work is mentioned, the
      presentations often contain errors of fact. To correct these shortcomings, we
      present an overview of his pre-1913 research that focuses on (1) his doctoral
      thesis and first book, Animal Education; (2) his studies with Harvey Carr on the
      role of the various sense modalities in rats' maze learning; (3) his
      collaboration with Robert Yerkes on the design and construction of psychophysical
      equipment for the quantitative study of vision, and on experiments on the visual
      capabilities of monkeys, rabbits, rats, and birds; and (4) his extensive
      naturalistic studies in Florida on the behavior of noddy and sooty terns, parts
      of which anticipated better-known subsequent research on imprinting and
      instinctual drift. Watson's commitment to the development of an objective,
      natural science of behavior is clearly evident throughout his early research. In
      addition, his research shows that his range of interests and scientific
      sophistication are greater than typical descriptions of his work indicate.

PMID- 22478650
TI  - The basic importance of applied behavior analysis.
AB  - We argue that applied behavior analysis is relevant to basic research.
      Modification studies, and a broad range of investigations that focus on the
      precipitating and maintaining conditions of socially significant human behavior,
      have basic importance. Applied behavior analysis may aid basic researchers in the
      design of externally valid experiments and thereby enhance the theoretical
      significance of basic research for understanding human behavior. Applied research
      with humans, directed at culturally-important problems, will help to propagate
      the science of human behavior. Such a science will also be furthered by analogue
      experiments that model socially important behavior. Analytical-applied studies
      and analogue experiments are forms of applied behavior analysis that could
      suggest new environment-behavior relationships. These relationships could lead to
      basic research and principles that further the prediction, control, and
      understanding of behavior.

PMID- 22478651
TI  - Behaviorism: Are reports of its death exaggerated?
AB  - Despite reports that behaviorism is dead or dying, examination of the data
      indicates otherwise. The opinions of psychology historians, the number of
      professional associations devoted to behaviorism, and the increasing number of
      behavioral publications all support the conclusion that behaviorism is vital and
      growing.

PMID- 22478652
TI  - Behavioral biology.

PMID- 22478653
TI  - Observer drift: A drifting definition.

PMID- 22478654
TI  - News from now-here, 1986: A response to "News from nowhere, 1984".

PMID- 22478655
TI  - A fire in schermerhorn extension.

PMID- 22478656
TI  - The challenge of technology transfer: Buying in without selling out.
AB  - Highly effective technologies flowing from the discipline of behavior analysis
      have not been widely adopted, thus threatening the survival of the discipline
      itself. An analysis of the contingencies underlying successful technology
      transfer suggests the need for direct, empirical involvement in the marketplace
      in order to insure that the maximum demonstrable benefits reach the ultimate
      users. A successful example of this strategy of technology transfer is provided.
      Three areas of intense national concern-urban violence, illiteracy, and declining
      industrial productivity-provide immediate opportunities for the technologies of
      behavior analysis to secure the place of the discipline in the intellectual
      mosaic of the 21st century.

PMID- 22478657
TI  - Methodology, the matching law, and applied behavior analysis.
AB  - THE PRACTICAL VALUE OF THE QUANTITATIVE ANALYSIS OF BEHAVIOR IS LIMITED BY TWO
      METHODOLOGICAL CHARACTERISTICS OF THIS AREA OF RESEARCH: the use of (a) steady
      state strategies and (b) relative vs. absolute response rates. Applied behavior
      analysts are concerned with both transition-state and steady-state behavior, and
      applied interventions are typically evaluated by their effects on absolute
      response rates. Quantitative analyses of behavior will have greater practical
      value when methods are developed for their extension to traditional rate-of
      response variables measured across time. Although steady-state and relative-rate
      of-response strategies are appropriate to the experimental analysis of many
      behavioral phenomena, these methods are rarely used by applied behavior analysts
      and further separate the basic and applied areas.

PMID- 22478658
TI  - Understanding cognitive language: The mental idioms in children's talk.
AB  - Considerable debate has occurred among behavior analysts about the value of
      cognitive language for labels or descriptions of phenomena in the analysis of
      behavior. That value is difficult to assess, however, until a clearer
      understanding of the definitions of those terms is obtained. To begin that
      process, this article demonstrates through a series of examples what children
      mean when they use typical cognitive expressions. One conclusion possible from
      the results of such an analysis is that cognitive terms describe nothing more
      than behavior in context, a very behavioral idea. Cognitive expressions may be
      more suitable to a behavioral analysis than to one derived from the current
      computer metaphor of cognitive science. The usefulness of these more accurately
      defined cognitive expressions for the scientific language of behavior analysis is
      discussed.

PMID- 22478659
TI  - The behavioral and the mystical: Reflections on behaviorism and eastern thought.
AB  - As in the case of other scientific conceptual schemas, features of radical
      behaviorism can be compared to descriptions of the world that have evolved within
      Eastern philosophic traditions. Applications of the analysis of verbal behavior
      can further the move within contemporary scientific writing towards calling
      attention to the structuring and limiting effects of language, effects long
      recognized in the East as sources of dualism and mentalism. Use of the three-term
      contingency automatically integrates organism and environment. Radical behavioral
      analyses can help demystify the mystical.

PMID- 22478660
TI  - Mentalism, behavior-behavior relations, and a behavior-analytic view of the
      purposes of science.
AB  - In a behavioral view, the purposes of science are primarily prediction and
      control. To the extent that a scientist embraces both of these as a unified and
      generally applicable criterion for science, certain philosophical and theoretical
      practices are counterproductive, including mentalism in both its metaphysical and
      metatheoretical forms. It is possible and often worthwhile to recast some
      mentalistic talk into an issue of behavior-behavior relations. When behavior
      behavior relations are approached non-mechanistically, however, analysis cannot
      stop at the level of the relations themselves. Several analytic concepts common
      in the behavioral community share some of the dangers of mentalism if not
      employed properly, including such concepts as self-reinforcement, response
      produced stimulation, and self-rules.

PMID- 22478662
TI  - He has acted to save the world: Award to Marlin Schneider, Wisconsin state
      representative.

PMID- 22478661
TI  - The ABA award for outstanding legislative action: Introduction of the presenter.

PMID- 22478663
TI  - Behavior, psychology, and praxics: Where does science fit in?

PMID- 22478664
TI  - Behaviorology: An integrative denomination.

PMID- 22478665
TI  - On praxis and praxics.

PMID- 22478667
TI  - Small investments, big payoffs.

PMID- 22478666
TI  - Left and right paths for behaviorism's development.

PMID- 22478668
TI  - Choosing the right tool.

PMID- 22478669
TI  - Traversing the Landscape Of Project BioShield.

PMID- 22478671
TI  - Approvals, FDA actions, clinical trials.

PMID- 22478670
TI  - MAYA-II and Molecular Computing.

PMID- 22478672
TI  - Phase 4 research grows despite lack of FDA oversight.

PMID- 22478673
TI  - 5 things employers want to know about biologics.
AB  - Can a determination of the value of biologics really be boiled down to a handful
      of issues? According to our sample of purchasers, the number of issues that
      really counts in the realm of biologics is just 5.

PMID- 22478674
TI  - Where VC Fears To Tread.
AB  - In recent years, venture capitalists have been less willing to place bets on pre
      clinical technologies. Major drug manufacturers, flush with cash but increasingly
      bereft of blockbusters, are stepping into the breach. So are established biotech
      companies. Here's a look at how the changing sources and timing of investments
      are helping to shape biotech's future.

PMID- 22478675
TI  - Biogenetic tests emerge from their chrysalis.
AB  - As technology improves, barriers to payment are beginning to fall for costly
      diagnostic tests that may identify good candidates for even pricier therapies.
      Part 1 of 2.

PMID- 22478676
TI  - Learning to love your specialty pharmacy: perspectives on a new business
      relationship.
AB  - The key to a smooth relationship lies in understanding the SP's capabilities and
      determining its role in your organization's success.

PMID- 22478677
TI  - A Renewed Emphasis on Therapeutic Angiogenesis Research for CAD.
AB  - Up to now, unblocking clogged arteries for so-called no-option patients with
      coronary artery disease or congestive heart failure hasn't been possible.
      Angiogenesis research, despite previous setbacks, may be the answer for this
      group of patients.

PMID- 22478678
TI  - Biologics Provide Hope For Immune System Disorders: Patients tell the story and
      ask for appropriate access.

PMID- 22478679
TI  - Specialty drugs continue to drive spending growth.

PMID- 22478680
TI  - Some predictions for 2008.

PMID- 22478681
TI  - The biotech detail rep of the future.

PMID- 22478682
TI  - Money-Back Guarantees: Where Private Payers Might Not Wait for CMS To Lead.

PMID- 22478685
TI  - Employers work to manage biologics in 2008 benefit designs.

PMID- 22478686
TI  - A century in the making... almost here?
AB  - Cancer immunotherapeutics, including vaccines, may hit the market by the end of
      this decade. They promise longer survival and perhaps indefinite remission at a
      more favorable cost-benefit ratio than that of oncologics now in use. They also
      may fuel dramatic changes in how healthcare is delivered and financed.

PMID- 22478683
TI  - Ousting the "ouch factor" in drug delivery.

PMID- 22478684
TI  - Approvals, FDA actions, clinical trials.

PMID- 22478687
TI  - Convergence in the midst of competition.
AB  - As biotechs hit their adolescence, they - like test makers and pharmaceutical
      manufacturers - are more likely than ever to reach outside of their own areas of
      expertise, link hands with the other guys, and pursue new programs and
      technologies.

PMID- 22478688
TI  - Biopharmaceuticals: the economic equation.
AB  - As more biopharmaceuticals reach the market, more attention will be given to
      issues such as cost-effectiveness evaluations, biosimilars, and price controls.
      The value biologic therapies bring to the healthcare system may take years to
      appreciate in full -perhaps only when policy decisions allow for their economic
      effects to be understood.

PMID- 22478689
TI  - A wish list for molecular tests.
AB  - Companion diagnostics improve health outcomes, say developers, who are willing to
      work with payers to develop medical policies for coverage. Payers and clinicians
      want more evidence of long-term benefit. The FDA, meanwhile, is jostling for
      regulatory control. How long will patients have to wait? Part 2 of 2.

PMID- 22478691
TI  - Making an impression on biotech development.

PMID- 22478690
TI  - Lower cost and faster product approval through proper software design controls.
AB  - The market success of a medical device depends in large part on how well its
      software is programmed. Focusing heavily on the device while treating the
      software as an afterthought can lead to costly recalls and liability concerns.

PMID- 22478692
TI  - Additional indications drive higher specialty spending.

PMID- 22478693
TI  - Winds of change.

PMID- 22478694
TI  - The savvy shopper.

PMID- 22478695
TI  - Research, conferences, and FDA actions.

PMID- 22478696
TI  - What the devil is personalized medicine?

PMID- 22478697
TI  - Solid tumors: prevalence, economics, and implications for payers and purchasers.
AB  - Prevalence of disease, economics of care, and implications for payers, as told in
      charts.

PMID- 22478699
TI  - Tumor marker: a new standard of breast cancer care.
AB  - Diagnostic test creation often requires using many of the principles of drug
      development. Complex data analysis and evidence-based reviews are changing
      professional society guidelines and treatment options for breast cancer.

PMID- 22478698
TI  - Translating cancer trial endpoints into the language of managed care.
AB  - Oncology endpoints are an essential component of cancer trials, but often they
      are confusing, making it difficult to evaluate cancer therapies based on trial
      data. As more oncology agents hit the market and as indications expand for
      existing products, familiarity with these endpoints is critical for payers when
      making coverage decisions.

PMID- 22478700
TI  - A Day in the Life: They Provide the Proof When Tough Decisions Have to be Made.
AB  - In a perfect world, payers would hire decision makers with a combination of
      attributes: a scientific understanding of biologics, the ability to get along
      with physicians, and managed care smarts. Meet SelectHealth's biologics go-to
      team.

PMID- 22478701
TI  - Flexibility in biologic benefit designs can deliver big rewards.
AB  - Some pioneering companies are making it easier for their employees to gain access
      to needed medications, regardless of the drug's acquisition cost. The hope is
      that easing the financial burden on employees will result not only in happier
      workers, but more productive ones as well.

PMID- 22478702
TI  - MRSA: The Private-Sector Response.
AB  - With Medicare eliminating payment for the treatment of several preventable
      hospital errors and infections, the market for effective infection-control
      interventions is poised to grow quickly. Products that merge information
      technology with biotechnology can improve quality of care, reduce unnecessary
      suffering, and eliminate waste of resources.

PMID- 22478703
TI  - Out-of-Pocket Expenses Can Soar With 4th-Tier Drugs.

PMID- 22478704
TI  - Olympian feats.

PMID- 22478705
TI  - Point with pride, view with alarm, end with hope.

PMID- 22478706
TI  - Research, conferences, and FDA actions.

PMID- 22478707
TI  - Is there a better way to guide payers on off-label coverage?

PMID- 22478708
TI  - Rheumatoid arthritis: prevalence, economics, and implications for payers and
      purchasers.
AB  - Prevalence of disease, economics of care, and implications for payers, as told in
      charts.

PMID- 22478709
TI  - 10 years, still shifting gears.
AB  - Ten years into the modern biologics era, access- and cost-management techniques
      still aren't refined. Why has managing biologics proven so much harder than
      managing other drugs? What strategies might help payers face the challenges of
      the future?

PMID- 22478710
TI  - What path do we take?
AB  - As existing biologics gain indications and new drugs make it to market, the array
      of choices makes it challenging to pick the right treatment for a given patient.
      Clinical effectiveness is the most important factor, but at the policy level,
      cost has to enter the discussion. Where?

PMID- 22478711
TI  - The next generation: strong, specialized.
AB  - The first generation of RA biologics was good, but just the start. A new group of
      therapies - some novel, some familiar, but all powerful and each with a niche -
      will energize this market.

PMID- 22478713
TI  - Health insurance you can bank on.
AB  - Robin Smith, MD, MBA, isn't claiming she has found the fountain of youth, but she
      is certain her company, NeoStem, can help prevent many costly, debilitating
      scourges of older age.

PMID- 22478712
TI  - The impact of rheumatoid arthritis and biologics on employers and payers.
AB  - Paresh Chaudhari, PharmD, MPH, frames the business case for employers to look
      beyond the direct medical costs of treatment of RA and consider employee health
      benefits as an investment.

PMID- 22478714
TI  - The evolution of specialty pharmacy.

PMID- 22478715
TI  - Under the Hood: GM's Strategy For Making Biologics Accessible.

PMID- 22478716
TI  - Declaring war on warfarin misdosing.

PMID- 22478717
TI  - Growth of specialty drug utilization slows over 4 years.

PMID- 22478718
TI  - This is What Matters.

PMID- 22478719
TI  - Industry profile.

PMID- 22478720
TI  - MS: Prevalence, Economics, and the Pipeline.
AB  - Prevalence of disease, economics of care, and implications for payers, as told in
      charts.

PMID- 22478721
TI  - Research, conferences, and FDA actions.

PMID- 22478722
TI  - Can online genetic testing predict the future?

PMID- 22478723
TI  - How the Candidates' Positions Indirectly Affect Access to and Financing of High
      Tech Therapies: Four healthcare experts handicap the reform proposals.
AB  - Nobody is out on the hustings talking about cost-sharing or fair means of access
      to biologics. But a pipeline loaded with them may ultimately force the government
      to address fundamental cost issues in healthcare. How the candidates' positions
      play into this.

PMID- 22478724
TI  - HER2 TESTS: How Do We Choose?
AB  - Incorrect test results defining HER2 status are not uncommon. Getting it wrong
      leads to spending a fortune on treatment that won't work or denying therapy to
      people whose lives could be spared by it.

PMID- 22478725
TI  - Trends, issues, and perspectives.
AB  - The nature of multiple sclerosis and its treatment differ from some other
      conditions that are treated with biologics, leading to opportunities that could
      help to close gaps in patient care.

PMID- 22478726
TI  - High-tech, simple solutions for improving patient care management.
AB  - Nonadherence is an incredibly complex and difficult-to-address problem. Several
      products designed to appeal to tech-savvy patients offer the promise of one
      simple solution.

PMID- 22478727
TI  - Cost-effectiveness: an evolving science.
AB  - Overseas, government payers challenge biopharma companies to show evidence of
      cost-effectivess. Collaboration there could provide a model for U.S. payers and
      manufacturers.

PMID- 22478728
TI  - The value of value-added services.

PMID- 22478729
TI  - Peeling back the onion.

PMID- 22478730
TI  - Is It Time To Take a Harder Look at the QALY?

PMID- 22478731
TI  - Biologics sales trends nearly double those of traditional pharmaceuticals.

PMID- 22478732
TI  - Unintended consequences.

PMID- 22478733
TI  - Birthday boomer.

PMID- 22478734
TI  - Role of genetic data emerges in antismoking effort.

PMID- 22478735
TI  - Digestive diseases: epidemiology, economics, and the pipeline.
AB  - Prevalence of disease, economics of care, the drug development pipeline, and
      implications for payers.

PMID- 22478736
TI  - Research, conferences, and FDA actions.

PMID- 22478737
TI  - VEBAs employers to unions: see if you can do better.
AB  - Faced with staggering healthcare costs, some large companies have transferred
      those liabilities to a voluntary employee beneficiary association. Eager to
      control employee and retiree benefits, unions gladly have taken on the challenge
      of running a VEBA. But success in this field is hard won, and to earn it, some
      unions may be forced to take a harder line with health care professionals and
      manufacturers than employers did.

PMID- 22478738
TI  - Creating a pathway over the regulatory chasm: a fresh start.
AB  - With the election over, a clear framework for guiding follow-on biologics to
      market may soon emerge. But difficult issues of cost, timing, and even
      terminology are keeping innovators and generic rivals on opposite sides of the
      fence.

PMID- 22478739
TI  - Making the case for biotechnology Reinsurance (BIO-RE).
AB  - The inherent difficulty of sustaining the rate of growth in healthcare spending
      may make biologics a touchstone for government intervention. The author proposes
      a combined cost-management and care-delivery standard that could lessen that
      threat.

PMID- 22478740
TI  - To manage costs of hemophilia, patients need more than clotting factor.
AB  - With the cost of clotting factor exceeding $50,000 a year, careful management can
      save payers thousands of dollars per patient. The author writes about the role
      specialty pharmacy plays in cost management while helping patients achieve better
      clinical outcomes.

PMID- 22478741
TI  - Copayment foundations: help for the underinsured.
AB  - With focus often placed on the uninsured, many patients who are underinsured fall
      through the cracks. Copayment foundations look to fill their gaps in coverage.

PMID- 22478742
TI  - When it comes to SP, employer size matters.

PMID- 22478744
TI  - Biotech drug development jumps 51 percent in 2 years.

PMID- 22478743
TI  - When a negative becomes a positive: GIC bucks the high-cost trend.

PMID- 22478745
TI  - The loch ness vaccine.

PMID- 22478746
TI  - Playing games.

PMID- 22478747
TI  - DTC Advertising: Where Do Genetic Tests Fit?

PMID- 22478748
TI  - Research, conferences, and FDA actions.

PMID- 22478750
TI  - Controlling the cost of care through clinical pathways.
AB  - A look at how two health plans have integrated physician-developed clinical
      pathways into their networks.

PMID- 22478749
TI  - Biologic vaccines: a panacea for infectious diseases?
AB  - The threat of new disease pandemics has spurred the development of biologic
      vaccines, which promise tremendous improvements in global and local health.
      Several lend themselves to the prevention or treatment of chronic diseases. But
      the uncertainties of whom to vaccinate raise the question of whether the health
      care system can make these promising products viable.

PMID- 22478751
TI  - Opportunity, resources, and affordability: multistakeholder perspectives.
AB  - On two occasions last year, the Jefferson School of Population Health convened a
      National Advisory Board of scientists and opinion leaders from key stakeholder
      groups at a high-level forum to explore different perspectives and to discuss
      improving access for patients who require treatment with biologic drugs. The
      following is the first of two articles documenting these discussions. The second
      article will appear in a subsequent issue of Biotechnology Healthcare.

PMID- 22478752
TI  - Payers tightening management of specialty therapies.
AB  - Continued market growth among specialty therapies has attracted the attention of
      big pharma and investors. Many payers, however, believe the industry has reached
      a tipping point, where greater management focus - and tougher decisions - are
      needed.

PMID- 22478753
TI  - Cutting back expenses through carve-outs.

PMID- 22478754
TI  - What's Learned When the Health Plan Is the Employer.

PMID- 22478755
TI  - More employees turning to high-deductible health plans.

PMID- 22478757
TI  - Congress must confront the biologic frontier.

PMID- 22478756
TI  - The Official Journal of BFAC.

PMID- 22478758
TI  - First-in-Class Product Seeks To Promote Better Prescribing Habits.

PMID- 22478759
TI  - Research, conferences, and FDA actions.

PMID- 22478761
TI  - Turning a blind eye to value.
AB  - Employers want value in benefit design. Why don't they get it?

PMID- 22478760
TI  - Genetic testing: Counselors Desperately Needed.
AB  - Genetic tests are proliferating, and payers, PBMs, and professional societies are
      developing in-house expertise to fill the counseling gap. All agree that more
      education programs and clinical decision tools are needed. But hard questions
      about data validity have to be answered first if personalized medicine is to
      become a reality.

PMID- 22478762
TI  - The push for prostate cancer screening.
AB  - New tests and techniques aim to alter the male mindset and raise public
      consciousness about this disease.

PMID- 22478763
TI  - What GINA Wants, Will GINA Get?
AB  - The new genetic nondiscrimination law took effect last month, but uncertainties
      remain.

PMID- 22478764
TI  - Rethinking comparative effectiveness research.
AB  - Opponents to the new CER legislation are raising red flags, warning about a one
      size-fits-all treatment approach and the rationing of healthcare. But Dr. Donald
      Berwick, president and CEO of the Institute for Healthcare Improvement, says to
      look at which interventions are effective - but not what they cost - is
      irrational and simply bad policy.

PMID- 22478766
TI  - Managing Second-line Biologics: Worth the Effort?

PMID- 22478765
TI  - Patient medication adherence: the forgotten aspect of biologics.
AB  - The full benefit of biologic therapies isn't reached and quality of life is
      compromised if patients don't adhere to their medication regimen. Are adherence
      interventions in order?

PMID- 22478767
TI  - Having mined gold in pharmacy deal, caterpillar sets sights on gold-standard
      therapies.

PMID- 22478768
TI  - Search for vaccines: opportunity in tragedy.

PMID- 22478769
TI  - The biggest thing since medicare.

PMID- 22478770
TI  - Getting our priorities straight.

PMID- 22478771
TI  - Genetic Tests Unravel Mystery of Long QT Syndrome.

PMID- 22478772
TI  - Research, conferences, and FDA actions.

PMID- 22478773
TI  - Walking the CER Path.
AB  - Evidence-based medicine has been a rallying cry for payers, but an inability to
      define value, conflicting clinical trial designs, physician practice variations,
      and payment incentives confound efforts to make EBM go mainstream. CER may give
      EBM some legs - just as the biologics pipeline is about to overflow.

PMID- 22478774
TI  - Comparative effectiveness: the employer perspective.
AB  - Biopharmaceuticals are rapidly emerging as a focal point of concern in benefit
      design. CE initiatives may prove their value, but controlling costs will be up to
      consumers.

PMID- 22478775
TI  - Building a value-based approach to biologic drugs.
AB  - In the absence of comprehensive position papers from professional organizations
      on the complex issue of patient affordability of biologic therapies, the
      Jefferson School of Population Health reconvened a National Advisory Board to
      discuss the issue. The objectives of the board were to quantify the issues and to
      identify potential solutions - including a recommended approach for payers.

PMID- 22478776
TI  - Industry meeting demands for more effective vaccines.
AB  - Swine flu aside, infectious disease is big business. Not all biopharma work is
      focused on rare diseases; new adjuvants and higher doses may be the answer to
      better flu control.

PMID- 22478778
TI  - Personalized Medicine: Tomorrow's Promise or Today's Reality?

PMID- 22478777
TI  - Specialty pharmacy trends and plan sponsor value.
AB  - Current benefit designs can't handle the increasing use and cost of biologic
      therapies. New tactical strategies to forge value-based insurance are needed now.

PMID- 22478779
TI  - Weeding out waste in benefit design.

PMID- 22478780
TI  - Specialty drugs, healthcare costs rise in tandem.

PMID- 22478781
TI  - Does healthcare warrant a warranty?

PMID- 22478782
TI  - In time for nanotech.

PMID- 22478783
TI  - Gene patents on the line.
AB  - Whoever invents or discovers any new and useful process, machine, manufacture, or
      composition of matter, or any new and useful improvement thereof, may obtain a
      patent therefor, subject to the conditions and requirements of this title. Patent
      Statute (USC 35, Part II, Chapter 10, Section 101).

PMID- 22478785
TI  - A crash course.
AB  - Researchers raced to fight the H1N1 pandemic, but translating knowledge to
      practice has proven to be difficult. Manufacturing capabilities have been
      hindered, distribution strategies have to be clarified, and public misconceptions
      need to be dispelled.

PMID- 22478784
TI  - Satisfaction GuaranteedOr Your Money Back.
AB  - Risk sharing is an old idea that has taken many forms in the era of managed care.
      But with the emergence of high-cost biopharmaceuticals, payers and purchasers are
      keen on a new twist: putting the onus on manufacturers to prove that their
      products are as good as advertised. Popular in Europe, risk-sharing contracts are
      gaining traction in the United States.

PMID- 22478786
TI  - Influenza vaccination: financial burden or public health solution?
AB  - Influenza drives up both direct and indirect costs for employers. Vaccinating
      employees can help with prevention, but the answer to keeping costs down may be
      herd immunity.

PMID- 22478787
TI  - FTC Versus Congress: The Biosimilars Debate.
AB  - A Federal Trade Commission report dismissed the need for a period of market
      exclusivity for brand-name biologics that may face follow-on competition. The
      authors argue that the FTC's conclusion -that patent protection alone will fuel
      biotech R&D after passage of follow-on legislation - is shaky.

PMID- 22478788
TI  - A rich pipeline that needs to be managed.
AB  - Health plans will experience increasing demands as specialty drugs are used for
      more common conditions. The author discusses ways to manage the ever-changing
      terrain.

PMID- 22478790
TI  - Can Higher PMPY Costs Be a Good Thing?

PMID- 22478789
TI  - Value-based insurance design.
AB  - As the healthcare debate waged on, many argued that VBID should be an essential
      component of reform. Payers and purchasers are looking to understand how VBID
      fits into the way services are chosen and paid for, maximizing the care given for
      the money spent.

PMID- 22478791
TI  - Ch... Ch... Changes...

PMID- 22478792
TI  - Think globally, act locally.

PMID- 22478793
TI  - KRAS Testing: Optimizing Cancer Therapy.

PMID- 22478794
TI  - Research, conferences, and FDA actions.

PMID- 22478795
TI  - Stacking hope against dollars.
AB  - When it comes to treating cancer, physicians pull out all the stops. In the face
      of escalating and exorbitant costs, though, what works and what doesn't must be
      sorted out.

PMID- 22478796
TI  - Copayment subsidies.
AB  - Payers are struggling to find an appropriate way to respond to copayment
      subsidies. Aggressive tactics to counteract them run the risk of keeping drugs
      from people who need them.

PMID- 22478797
TI  - Cost-sharing reform: searching for equity.
AB  - The healthcare reform debate has included discussion of some cost relief for
      patients by subsidizing their out-of-pocket costs. But employers and payers are
      looking at other options, such as linking the value of a healthcare intervention
      to its copayment, to try to improve health-care delivery and make its cost more
      equitable for all.

PMID- 22478798
TI  - The impact of the patient-centered medical home on the biologics industry,
      employers, and third-party payers.
AB  - A strong primary care system is a critical element of healthcare, but its current
      state is anything but efficient. One promising model of change is the patient
      centered medical home.

PMID- 22478799
TI  - IOM Likes Its CER List; Others Might if It Suits Them.
AB  - The Institute of Medicine, charged with helping health plans and providers choose
      best treatments, suggests 100 priorities for CER research interest. The use of
      biologics or the study of biomarkers make up just 4 of the 100 priorities.

PMID- 22478801
TI  - Adherence: A Measure of ROI.

PMID- 22478800
TI  - Mixing Personalized Medicine and CER, One Specialty Pharmacy Plows New Ground.

PMID- 22478802
TI  - The shell game as healthcare reform.

PMID- 22478803
TI  - Beware biohacking?

PMID- 22478804
TI  - Familial hypercholesterolemia captures gene test controversies.

PMID- 22478805
TI  - Research, conferences, and FDA actions.

PMID- 22478806
TI  - It's the System, Stupid: How Systems Biology Is Transforming.
AB  - So far, little is known about systems biology and its potential for changing how
      we diagnose and treat disease. That will change soon, say the systems experts,
      who advise payers to begin learning now about how it could make healthcare
      efficient.

PMID- 22478807
TI  - Payer perspectives on federally funded comparative effectiveness research.
AB  - Comparing the effectiveness of drugs and their costs is not new for payers, whose
      criteria may include factors not considered by investigators performing federally
      funded CER. Here are the surprising results of a survey of payer views on the
      impact of federal CER on specialty drugs.

PMID- 22478809
TI  - Breaking down the barriers to biologics.

PMID- 22478808
TI  - How a patent eligibility case could affect personalized medicine.
AB  - Personalized medicine may be in danger as the doctrine of patent eligibility 
      which determines technological innovations that warrant patent protection -faces
      legal challenges. Diagnostic tests, gene patents, and more are at stake.

PMID- 22478810
TI  - Wellness programs on the rise.

PMID- 22478811
TI  - Employee cost share rises; employers still paying more.

PMID- 22478812
TI  - Of risks and dreams.

PMID- 22478813
TI  - Entry and exit.

PMID- 22478814
TI  - Surprise District Court Ruling Invalidates Myriad Genetics' BRCA Patents, But
      Appeal is Pending.

PMID- 22478815
TI  - Clinical trials, research, and FDA actions.

PMID- 22478816
TI  - Managing the immunomodulators.
AB  - Dosage and indication "creep" with the new biologics to treat inflammatory
      diseases have payers enforcing strict utilization policies. Physicians counter
      that payers can't dictate treatment. With even more biologics on the horizon, and
      drug spend spiralling upward, both sides need to seek a middle ground. The
      question is how?

PMID- 22478817
TI  - The value of observational cohort studies for cancer drugs.
AB  - Randomized controlled trials - the gold standard for clinical drug evaluation 
      can't always predict adverse events in real-world settings. For the new cancer
      therapies, observational cohort studies (OCSs) can help evaluate their effects in
      broader populations and provide valuable information for future clinical trials.

PMID- 22478819
TI  - Diagnostics come of age.

PMID- 22478818
TI  - Medical devices: adapting to the comparative effectiveness landscape.
AB  - Outcomes research for medical devices has always lagged, with good reason.
      Comparative effectiveness initiatives, though, will soon spur demand for more and
      better data, and that means more and better outcomes research training.

PMID- 22478820
TI  - With injectable biologic therapies on the rise, payers face tough reimbursement
      issues.

PMID- 22478821
TI  - Inception.

PMID- 22478822
TI  - Strategic decision making.

PMID- 22478824
TI  - Clinical trials, research, and FDA actions.

PMID- 22478823
TI  - P4 medicine could transform healthcare, but payers and physicians are not yet
      convinced.

PMID- 22478825
TI  - Will Clinical Pathways Work?: Insurers say they are willing to give up control
      over what they pay for to reduce cancer costs. But oncologists may think
      differently.

PMID- 22478826
TI  - Oncology Biomarker Diagnostics: Where We Are, Where We Need To Be: Identifying
      cancer biomarkers that are clinically useful is difficult. So is obtaining
      funding to get biomarker diagnostics to market.

PMID- 22478827
TI  - Payers Try New Approaches To Manage Molecular Diagnostics: Some payers require
      prior authorization for molecular diagnostic testing and some don't. And some
      payers are looking at other options.

PMID- 22478828
TI  - Comparative effectiveness research: promise or peril for biotechnology?

PMID- 22478830
TI  - Specialty drug use and cost continue to rise.

PMID- 22478829
TI  - Specialty drug use among children and adolescents is growing.

PMID- 22478831
TI  - Show me the evidence.....

PMID- 22478833
TI  - Clinical trials, research, and FDA actions.

PMID- 22478832
TI  - Biology 2.0.

PMID- 22478834
TI  - If It's Not Type 1 or Type 2 Diabetes, It May be Monogenic Diabetes.

PMID- 22478835
TI  - Longing To Believe In Evidence-Based Medicine: Questions abound about the
      motivations of researchers who publish their work. But forces are converging to
      create a more transparent and user-friendly evidence base.
AB  - Justified or not, evidence-based medicine is again under attack. Critics claim
      the science is suspect and guidelines are often arbitrary. The push for a
      transparent, user-friendly evidence base - that also makes use of real-world data
      - has started, giving hope to payers for evidence they can depend on.

PMID- 22478836
TI  - Seeking a Coding Solution For Molecular Tests: Managing the estimated 1,700
      molecular tests now on the market is impossible without a unique CPT code for
      each test. What's at stake? The future of personalized medicine.
AB  - The lack of a unique CPT code for each molecular test on the market jeopardizes
      patient test results and the evidence base. It's time for a serious overhaul.

PMID- 22478837
TI  - The Biosimilars Act: Promoting or Discouraging the Development of Generic
      Biologics?: A tug-of-war between generic and innovator biologics seems to be
      where drug developers are headed.
AB  - Congress may have unwittingly thrown roadblocks at makers of follow-on biologics.

PMID- 22478839
TI  - Oral multiple sclerosis agents look to gain market share.

PMID- 22478838
TI  - The need to serve rural america.
AB  - Biologics and the new diagnostics are needed in rural areas nationwide.

PMID- 22478840
TI  - Prior authorization - still used, still an issue.

PMID- 22478841
TI  - Serious games.

PMID- 22478842
TI  - Clinical trials, research, and FDA findings.

PMID- 22478843
TI  - New tests can identify the genetic mutations that drive lung cancers.

PMID- 22478844
TI  - Intervening on behalf of patients.
AB  - Adherence to a biologic treatment regimen is essential for tracking efficacy and
      justifying its cost. That's where medication therapy management services come
      in.Pharmacists are providing medication therapy management (MTM) services for
      patients taking biologics, although studies to demonstrate its cost-effectiveness
      are lacking. Is this the best way to ensure that high-cost, high-impact biologics
      are used correctly?

PMID- 22478845
TI  - Why Bigger Is Better For Controlling Oncology Spend: It offers less competition -
      perhaps - but can be a boon for evidence-based pathway initiatives.
AB  - Oncology practices nationwide face rising maintenance costs and lower
      reimbursements for biologic therapies. It's even tougher for small community
      based practices, which often lag in adopting new standards of cancer care. Group
      purchasing organizations claim they have the market clout that oncologists need,
      and McKesson is betting that they are right. Will the US Oncology buyout deliver?

PMID- 22478846
TI  - Alzheimer's disease: new therapies and the role of biomarkers.
AB  - Biomarkers have shown promise for identifying people at high risk for Alzheimer's
      disease. Therapies that address presymptomatic disease are already in
      development, and MCOs should start thinking about coverage for them.

PMID- 22478847
TI  - The 3.3 percent rx dilemma.

PMID- 22478848
TI  - Medical cost growth will slow in 2011.

PMID- 22478849
TI  - Breaking out of the spend game.

PMID- 22478850
TI  - Clinical trials, research, and FDA findings.

PMID- 22478851
TI  - Regulators place spotlight on drug prices.

PMID- 22478852
TI  - Lots of enthusiasm, lots of questions.
AB  - Value-based benefit design is all the rage, but applying it to biologics is
      complicated. Several issues must be addressed if VBBD is to rule this frontier.

PMID- 22478853
TI  - Putting a lid on chemotherapy costs.
AB  - Genomic Health's Oncotype DX Colon Cancer Assay assesses the risk of stage II
      colon cancer recurrence and potential adjuvant chemotherapy benefit. Cost savings
      could be huge.

PMID- 22478854
TI  - The biologic finance and access council 2nd annual biologics healthcare survey:
      views from key healthcare stakeholders.
AB  - Although biologics are a growing area of interest, payers, purchasers, and
      providers understand surprisingly little about their overall costs or benefits
      coverage.

PMID- 22478855
TI  - Managing MS: Trends, Issues, and Perspectives.
AB  - The entry of oral medications for multiple sclerosis into the marketplace and the
      high cost of biologic drugs are presenting new challenges for stakeholders.

PMID- 22478856
TI  - Resurrection of preterm labor drug evokes questions of fairness.
AB  - Big prices for small-market biopharmaceuticals is nothing new. But when the
      market is centered around a public health concern, pricing can trigger
      contentious issues.

PMID- 22478857
TI  - ScoliScore AIS Prognostic Test Personalizes Treatment for Children With Spinal
      Curve.

PMID- 22478858
TI  - Appropriate specialty drug utilization to reduce waste still a top priority.

PMID- 22478859
TI  - Pharmacy practice residencies in Canada: opportunities and emerging challenges.

PMID- 22478860
TI  - Effect of utilization policies for fluoroquinolones: a pilot study in nova scotia
      hospitals.
AB  - BACKGROUND: Antimicrobial resistance results in increased morbidity, mortality,
      and costs to the health care system. Evidence suggests an association between the
      use of antimicrobials in hospitals and the development of antimicrobial
      resistance. Fluoroquinolones constitute one group of antimicrobials that are
      effective against a variety of bacterial infections, yet they may be subject to
      misuse. Many hospitals in Nova Scotia have implemented policies to improve
      antimicrobial prescribing, but the impact of these policies on utilization is
      unknown. OBJECTIVES: To evaluate the use of fluoroquinolones in Nova Scotia
      hospitals using the World Health Organization's Anatomical Therapeutic Chemical
      classification system with defined daily doses (ATC/DDD) and to examine the
      influence of hospital policies for utilization of fluoroquinolones in community
      acquired pneumonia. METHODS: During the study period (April 1, 1997, to March 31,
      2003), fluoroquinolones were administered at 31 of the 37 hospitals in Nova
      Scotia's 9 district health authorities. Hospital administrative data, hospital
      characteristics, and pharmaceutical purchasing data related to use of these drugs
      were aggregated using the ATC/DDD methodology for the fiscal years 1997/1998 to
      2002/2003. District pharmacy directors were surveyed to obtain information about
      district and individual hospital antibiotic policies. Descriptive statistics were
      calculated, and univariable regression and multilevel analyses were performed.
      RESULTS: Mean overall fluoroquinolone use increased over the study period, from
      47.2 DDD/1000 bed-days per year in fiscal year 1997/1998 to 163.8 DDD/1000 bed
      days per year in fiscal year 2002/2003 (p < 0.001). Multilevel analysis showed
      that utilization policies aimed at appropriate prescribing did not affect the use
      of fluoroquinolones. CONCLUSION: This study revealed that drug purchasing,
      hospital administrative, and diagnostic data could be combined to compare the
      utilization of fluoroquinolones among different hospitals and district health
      authorities. Utilization policies had little effect on the amount, type, or route
      of fluoroquinolone use.

PMID- 22478861
TI  - Evaluation of the Accuracy of the Saskatchewan Health Pharmaceutical Information
      Program for Determining a Patient's Medication Use Immediately before Admission.
AB  - BACKGROUND: The Pharmaceutical Information Program (PIP) administered by
      Saskatchewan Health provides records for individual patients of prescription
      medications and some over-the-counter products obtained with a prescription and
      processed through the provincial drug plan. Use of the PIP to assist in obtaining
      a medication history on admission to hospital has been advocated; however, the
      accuracy of the database has never been investigated. OBJECTIVE: To quantify the
      extent of agreement between a patient's PIP profile and a Best Possible
      Medication History (BPMH) for determining the patient's prescription medication
      use on admission to hospital. METHODS: General medicine patients admitted to 1 of
      the 2 clinical teaching units at the authors' hospital were reviewed for
      eligibility. A copy of the patient's PIP profile was printed, reviewed, and used
      in the course of obtaining a BPMH from consenting patients. The number and type
      of medication discrepancies and the time required to complete medication
      histories were documented. RESULTS: Fifty patients were interviewed. For 39
      patients (78%), one or more prescription discrepancies were identified between
      the PIP profile and the BPMH (mean 2.0, standard deviation 2.3, range 0-6). The
      top 3 prescription discrepancies were medication incorrectly appeared inactive in
      the PIP profile (49/101 discrepancies [49%]), dosing discrepancy (28/101 [28%]),
      and medication did not appear in the PIP profile (13/101 [13%]). The most common
      reasons for prescription discrepancies were recent change in dosage or medication
      (18 [18%]), compliance packaging (13 [13%]), noncompliance (12 [12%]), and entry
      error at the dispensing pharmacy (12 [12%]). Mean total time to prepare for and
      conduct interviews was 22.5 min (range 10-54 min). CONCLUSION: A patient's PIP
      profile may contain incomplete, inaccurate, or misleading information. Although
      the profile may be used to prompt the health care provider during a BPMH
      interview, it should never be used as a substitute for communicating directly
      with the patient.

PMID- 22478862
TI  - Physical compatibility and chemical stability of ketamine-morphine mixtures in
      polypropylene syringes.
AB  - BACKGROUND: Small amounts of ketamine administered with a narcotic can help to
      reduce both requirements for and potential adverse effects of the opioid. The use
      of ketamine in conjunction with morphine has become popular with the Acute Pain
      Service of the author's hospital. However, the only reported stability data that
      have been found for this combination stored in syringes were for 6 days at room
      temperature. OBJECTIVE: To conduct a compatibility and stability study with the
      ultimate aim of extending the current expiry date for the concentrations of
      ketamine and morphine combinations used at the author's institution and thus to
      allow batch production of mixtures of these drugs without increasing wastage.
      METHODS: Commercial solutions of ketamine (50 mg/mL) and morphine sulphate (50
      mg/mL) were combined and further diluted with 0.9% sodium chloride to final
      concentrations of ketamine 2 mg/mL and morphine 2, 5, or 10 mg/mL; the resulting
      mixtures were packaged in polypropylene syringes. The syringes were stored at
      either 23 degrees C or 5 degrees C for 91 days. The following physical
      compatibility parameters were monitored: clarity, colour, and pH. Chemical
      stability was determined with a validated stability-indicating high-performance
      liquid chromatography system. RESULTS: Over the 91 days, all solutions remained
      clear and colourless, and the pH did not change significantly. The concentration
      of each drug in the various solutions remained above 98% of the original
      concentration for both storage conditions for the duration of the study.
      CONCLUSIONS: Solutions of ketamine (2 mg/mL) combined with morphine (2, 5, or 10
      mg/mL) were physically compatible and chemically stable for 91 days when diluted
      with normal saline, packaged in polypropylene syringes, and stored at either 23
      degrees C or 5 degrees C.

PMID- 22478864
TI  - Practice spotlight: eric lun.

PMID- 22478863
TI  - Long-term stability of 5-Fluorouracil in 0.9% sodium chloride after freezing,
      microwave thawing, and refrigeration.
AB  - OBJECTIVE: To investigate the stability of 5-fluorouracil diluted in 0.9% sodium
      chloride (normal saline [NS]) after freezing, microwave thawing, and storage for
      28 days at 5 degrees C +/- 3 degrees C. METHODS: Polyvinylchloride (PVC) infusion
      bags (n = 5) containing 5-fluorouracil 800 mg/100 mL were frozen for 79 days at 
      20 degrees C. The bags were then thawed in a microwave oven and stored at 5
      degrees C +/- 3 degrees C for 28 days. The concentration of 5-fluorouracil was
      measured by high-performance liquid chromatography. Visual and microscopic
      inspections were performed and pH was measured periodically during storage.
      Solutions were considered stable if the lower limit of the 95% confidence
      interval of the concentration versus time profile remained greater than 90% of
      the initial concentration. RESULTS: No colour change or precipitation was
      observed in any of the solutions. Slight changes in pH were observed during
      refrigeration. 5-Fluorouracil solutions were stable during storage at 5 degrees C
      +/- 3 degrees C for 28 days, as indicated by the results of high-performance
      liquid chromatography. CONCLUSION: 5-Fluorouracil 8 mg/mL in NS may be prepared
      in advance, frozen and stored in PVC bags, and thawed before use. The solutions
      remained stable after freezing at -20 degrees C for 79 days followed by storage
      at 5 degrees C +/- 3 degrees C for up to 28 days.

PMID- 22478865
TI  - A near miss involving cyclophosphamide.

PMID- 22478866
TI  - Is a 1-year residency program long enough to prepare hospital pharmacists for
      practice?

PMID- 22478868
TI  - St Mary's Hospital, Sechelt, British Columbia.

PMID- 22478867
TI  - In vitro study of esomeprazole sachet suspension administered via enteral feeding
      tubes.

PMID- 22478869
TI  - CSHP Professional Practice Conference 2009: Poster Abstracts/Conference sur la
      pratique professionnelle 2009 de la SCPH : Resumes des affiches.

PMID- 22478870
TI  - 2009 CSHP National Awards Program/Programme National Des Prix 2009 De La SCPH.

PMID- 22478871
TI  - The Times They Are a-Changin'.

PMID- 22478872
TI  - Practical education for pharmacist students: a hospital perspective.

PMID- 22478873
TI  - The pharmacist as patient educator.

PMID- 22478874
TI  - Cobequid community health centre, lower sackville, nova scotia.

PMID- 22478875
TI  - Survey of sterile admixture practices in canadian hospital pharmacies: part 1.
      Methods and results.
AB  - BACKGROUND: The 1996 Guidelines for Preparation of Sterile Products in Pharmacies
      of the Canadian Society of Hospital Pharmacists (CSHP) represent the current
      standard of practice for sterile compounding in Canada. However, these guidelines
      are practice recommendations, not enforceable standards. Previous surveys of
      sterile compounding practices have shown that actual practice deviates markedly
      from voluntary practice recommendations. In 2004, the United States Pharmacopeia
      (USP) published its "General Chapter <797> Pharmaceutical Compounding-Sterile
      Preparations", which set a more rigorous and enforceable standard for sterile
      compounding in the United States. OBJECTIVES: To assess sterile compounding
      practices in Canadian hospital pharmacies and to compare them with current CSHP
      recommendations and USP chapter <797> standards. METHODS: An online survey, based
      on previous studies of sterile compounding practices, the CSHP guidelines, and
      the chapter <797> standards, was created and distributed to 193 Canadian hospital
      pharmacies. RESULTS: A total of 133 pharmacies completed at least part of the
      survey, for a response rate of 68.9%. All respondents reported the preparation of
      sterile products. Various degrees of deviation from the practice recommendations
      were noted for virtually all areas of the CSHP guidelines and the USP standards.
      Low levels of compliance were most notable in the areas of facilities and
      equipment, process validation, and product testing. Availability in the central
      pharmacy of a clean room facility meeting or exceeding the criteria of
      International Organization for Standardization (ISO) class 8 is a requirement of
      the chapter <797> standards, but more than 40% of responding pharmacies reported
      that they did not have such a facility. Higher levels of compliance were noted
      for policies and procedures, garbing requirements, aseptic technique, and
      handling of hazardous products. Part 1 of this series reports the survey methods
      and results relating to policies, personnel, raw materials, storage and handling,
      facilities and equipment, and garments. Part 2 will report results relating to
      preparation of aseptic products, expiry dating, labelling, process validation,
      product testing and release, documentation, records, and disposal of hazardous
      pharmaceuticals. It will also highlight some of the key areas where there is
      considerable opportunity for improvement. CONCLUSION: This survey identified
      numerous deficiences in sterile compounding practices in Canadian hospital
      pharmacies. Awareness of these deficiencies may create an impetus for critical
      assessment and improvements in practice.

PMID- 22478876
TI  - Stability of Hydromorphone-Ketamine Solutions in Glass Bottles, Plastic Syringes,
      and IV Bags for Pediatric Use.
AB  - OBJECTIVES: To evaluate the stability of mixtures of hydromorphone and ketamine
      in 0.9% sodium chloride (normal saline [NS]) after storage for up to 7 days at
      room temperature (25 degrees C). METHODS: The stability of 3 standard mixtures of
      hydromorphone and ketamine (hydromorphone 0.2 mg/mL + ketamine 0.2 mg/mL,
      hydromorphone 0.2 mg/mL + ketamine 0.6 mg/mL, and hydromorphone 0.2 mg/mL +
      ketamine 1.0 mg/mL) in NS was studied. Portions of each mixture were transferred
      to 3 brown glass bottles (100 mL), 3 plastic syringes (50 mL), and 3 IV bags (50
      mL), which were then stored at room temperature (25 degrees C). Physical
      characteristics, including pH, colour, and precipitation, were evaluated daily.
      Three 1.5-mL samples were collected from each bottle, syringe, and IV bag at
      baseline, at 24, 48, and 72 hours, and on day 7. Samples were analyzed in
      triplicate by a stability-indicating high-performance liquid chromatography
      method. Solutions were considered stable if they maintained 90% of the initial
      concentration of each drug. Samples from syringes and IV bags were subjected to
      standard sterility testing by incubation for 5 days in an enriched culture media.
      RESULTS: No notable changes in pH or colour were observed, and no precipitation
      occurred in any of the solutions. All formulations maintained more than 90% of
      the initial concentration of each drug on day 7. No bacterial growth was observed
      in any of the samples tested. CONCLUSIONS: Mixtures of hydromorphone and ketamine
      were stable for up 7 days at 25 degrees C, and the sterility of the preparations
      was maintained. Because stability alone does not guarantee efficacy, it is
      recommended that clinical studies be conducted to evaluate the pharmacokinetics
      and pharmacodynamics of these formulations.

PMID- 22478877
TI  - Monitoring of serum prolactin in pediatric patients with cystic fibrosis who are
      receiving domperidone.
AB  - BACKGROUND: Since 2003, it has been routine practice at Children's and Women's
      Health Centre of British Columbia to monitor serum levels of prolactin in
      pediatric patients with cystic fibrosis who are receiving domperidone. Although a
      pharmacologic relationship between domperidone and prolactin has been documented
      in the literature, there is no information about routine monitoring of prolactin,
      and guidance on interpretation of prolactin values is lacking. OBJECTIVES: To
      characterize how prolactin levels were being used in monitoring patients with
      cystic fibrosis who were receiving domperidone therapy at this institution, to
      evaluate the need for this practice, and to formulate recommendations
      accordingly. METHODS: A chart review was conducted for pediatric patients with
      cystic fibrosis who had been receiving domperidone therapy and whose serum
      prolactin levels had been monitored between June 1, 2001, and October 1, 2005.
      RESULTS: A total of 219 samples had been drawn, from 49 patients, for
      determination of prolactin level. Of these, 100 (45.7%) were above the normal
      range. Of the values above the normal range, 86 (86%) led to no dosage adjustment
      of domperidone and 14 (14%) led to either a decrease in dose or discontinuation
      of therapy. None of the elevated prolactin levels were associated with
      supratherapeutic doses of domperidone. CONCLUSION: The role of routine monitoring
      of prolactin in this patient population requires further study. In particular,
      more information is needed about prolactin levels in pediatric patients and the
      relationship of prolactin level to domperidone dose.

PMID- 22478878
TI  - Clinical Equivalency of Ciprofloxacin 750 mg Enterally and 400 mg Intravenously
      for Patients Receiving Enteral Feeding: Systematic Review.
AB  - BACKGROUND: Concomitant enteral administration of ciprofloxacin with products
      containing magnesium, aluminum, and calcium (e.g., as enteral feeds) decreases
      the oral bioavailability of this antibiotic. The manufacturer currently
      recommends holding enteral feeds for a total of 8 h after ciprofloxacin is given,
      but this is not feasible for patients who are receiving continuous enteral
      feeding. A previous study demonstrated that a higher dose of oral ciprofloxacin
      (750 mg BID) may compensate for the reduced bioavailability associated with this
      drug-food interaction, allowing adequate concentrations for effective
      bactericidal activity. OBJECTIVE: To evaluate whether ciprofloxacin 750 mg
      administered enterally is a clinically feasible alternative to ciprofloxacin 400
      mg administered intravenously for adults receiving enteral feeds. METHODS: A
      literature search was conducted in EMBASE (January 1980 to April 2008) and
      MEDLINE (January 1949 to April 2008), with no language restrictions, using the
      key words "ciprofloxacin", "fluoroquinolone", "tube feed", and "enteral". For
      trials that remained after screening of the abstract, the full text was reviewed
      and the reference lists were hand-searched to identify additional trials. The
      following outcomes were prespecified: death, serious adverse events, clinical
      cure, microbiological cure, re-infection, total adverse events, ratio of area
      under the curve (AUC, in microgram-hours per millilitre) to minimum inhibitory
      concentration (MIC, in micrograms per millilitre), ratio of maximum serum
      concentration (C(max), in micrograms per millilitre) to MIC, and C(max). RESULTS:
      The search identified 121 potentially eligible studies, which were screened on
      the basis of information provided in the abstract. From this initial screening,
      it was clear that 113 studies did not meet the inclusion criteria. The remaining
      8 studies were subjected to a full-text review, which revealed that only 1 study
      met the inclusion criteria. In that study, ciprofloxacin 750 mg given enterally
      yielded an AUC similar to that achieved with 400 mg given parentally, but the
      C(max) was lower. No clinical outcomes were reported. CONCLUSIONS: There is
      insufficient evidence from this systematic review to determine whether patients
      receiving enteral feeds concomitantly with enteral ciprofloxacin 750 mg BID will
      achieve clinical outcomes similar to those receiving parenteral ciprofloxacin 400
      mg BID.

PMID- 22478879
TI  - Extended stability of pantoprazole for injection in 0.9% sodium chloride or 5%
      dextrose at 4 degrees c and 23 degrees c.
AB  - BACKGROUND: The pantoprazole product available in Canada for IV administration
      has recently been reformulated to include ethylenediaminetetra-acetic acid
      (EDTA). The purpose of this study was to determine if the chemical stability of
      pantoprazole for injection containing EDTA (PANTO IV), admixed in polyvinyl
      chloride (PVC) minibags at concentrations of 0.16 mg/mL and 0.80 mg/mL in 5%
      dextrose in water (D5W) or 0.9% sodium chloride for injection (normal saline
      [NS]) and stored at 4 degrees C or 23 degrees C, could be extended beyond the
      manufacturer's expiry period of 24 hours. METHODS: Sodium pantoprazole was
      reconstituted in NS or D5W, and 32 PVC minibags were prepared, 16 containing
      pantoprazole at a nominal concentration of 0.16 mg/mL (8 in NS, 8 in D5W) and 16
      containing pantoprazole at a nominal concentration of 0.80 mg/mL (8 in NS, 8 in
      D5W). Half of the minibags for each diluent-concentration combination were stored
      at 4 degrees C and half at room temperature (23 degrees C). The concentration of
      pantoprazole in each minibag was determined by a validated, stability-indicating
      liquid chromatographic method on study days 0, 1, 2, 4, 7, 9, 11, 14, and 21.
      RESULTS: Analysis of variance revealed differences in the percentage of drug
      remaining in relation to temperature (p < 0.001), study day (p = 0.001),
      concentration (p = 0.007), and diluent (p = 0.008). CONCLUSIONS: Solutions of
      pantoprazole in D5W with concentration between 0.16 mg/mL and 0.80 mg/mL can be
      stored for a maximum of 11 days at 4 degrees C plus an additional 6 h at 23
      degrees C. The saline solutions degraded more slowly, and pantoprazole admixtures
      in NS with concentration between 0.16 mg/mL and 0.80 mg/mL can be stored for 20
      days at 4 degrees C plus an additional 6 h at 23 degrees C. Under these
      conditions, more than 90% of the initial concentration will remain (with 95%
      confidence).

PMID- 22478880
TI  - Clostridium difficile Outbreak: A Small Group of Pharmacists Makes a Big Impact.

PMID- 22478881
TI  - Practice Spotlight: Marie Craig and The Arthritis Program (TAP) at Southlake
      Regional Health Centre.

PMID- 22478882
TI  - Enhancing safe medication use for pediatric patients in the emergency department.

PMID- 22478883
TI  - Does colour-coded labelling reduce the risk of medication errors?

PMID- 22478885
TI  - Tribute to the reviewers of the canadian journal of hospital pharmacy.

PMID- 22478884
TI  - Notice to Hospitals Regarding Ceftriaxone-Calcium Incompatibility: What's a
      Clinician to Do?

PMID- 22478886
TI  - Distinguished service award 2008/2009 presented by ortho biotech - division of
      janssen-ortho inc robin j ensom.

PMID- 22478887
TI  - Care Beyond Cure: Management of Pain and Other Symptoms: Published in
      collaboration with l'Association des pharmaciens des etablissements de sante du
      Quebec (A.P.E.S.) and the Canadian Society of Hospital Pharmacists (CSHP).

PMID- 22478888
TI  - Technological Disintermediation: A Path to CSHP 2015 and Beyond.

PMID- 22478889
TI  - Information Overload: We Need to Improve the Signal-to-Noise Ratio.

PMID- 22478890
TI  - Survey of sterile admixture practices in canadian hospital pharmacies: part 2.
      More results and discussion.
AB  - BACKGROUND: The 1996 Guidelines for Preparation of Sterile Products in Pharmacies
      of the Canadian Society of Hospital Pharmacists (CSHP) represent the current
      standard of practice for sterile compounding in Canada. However, these guidelines
      are practice recommendations, not enforceable standards. Previous surveys of
      sterile compounding practices have shown that actual practice deviates markedly
      from voluntary practice recommendations. In 2004, the United States Pharmacopeia
      (USP) published its "General Chapter <797> Pharmaceutical Compounding-Sterile
      Preparations", which set a more rigorous and enforceable standard for sterile
      compounding in the United States. OBJECTIVES: To assess sterile compounding
      practices in Canadian hospital pharmacies and to compare them with current CSHP
      recommendations and USP chapter <797> standards. METHODS: An online survey, based
      on previous studies of sterile compounding practices, the CSHP guidelines, and
      the chapter <797> standards, was created and distributed to 193 Canadian hospital
      pharmacies. RESULTS: A total of 133 pharmacies completed at least part of the
      survey, for a response rate of 68.9%. All respondents reported the preparation of
      sterile products. Various degrees of deviation from the practice recommendations
      were noted for virtually all areas of the CSHP guidelines and the USP standards.
      Low levels of compliance were most notable in the areas of facilities and
      equipment, process validation, and product testing. Availability in the central
      pharmacy of a clean room facility meeting or exceeding the criteria of
      International Organization for Standardization (ISO) class 8 is a requirement of
      the chapter <797> standards, but more than 40% of responding pharmacies reported
      that they did not have such a facility. Higher levels of compliance were noted
      for policies and procedures, garbing requirements, aseptic technique, and
      handling of hazardous products. The survey methods for this study and results
      relating to policies, personnel, raw materials, storage and handling, facilities
      and equipment, and garments were reported in Part 1. Part 2 reports results
      relating to preparation of aseptic products, expiry dating, labelling, process
      validation, product testing and release, documentation, records, and disposal of
      hazardous pharmaceuticals. It also highlights some of the key areas where there
      is considerable opportunity for improvement. CONCLUSION: This survey identified
      numerous deficiencies in sterile compounding practices in Canadian hospital
      pharmacies. Awareness of these deficiencies may create an impetus for critical
      assessment and improvements in practice.

PMID- 22478891
TI  - Prevalence and satisfaction of discharged patients who recall interacting with a
      pharmacist during a hospital stay.
AB  - BACKGROUND: To enhance the quality of patient care, the former Calgary Health
      Region (now part of Alberta Health Services) works continuously to improve
      pharmacy clinical services and to plan and implement new programs and services.
      Patient satisfaction is an important indicator of patients' perception of the
      value of services provided. OBJECTIVES: To determine the baseline prevalence of
      patients admitted to the former Calgary Health Region with complex and high-risk
      medication needs who recalled speaking to a pharmacist during their hospital stay
      and their reported satisfaction with those interactions. METHODS: A retrospective
      cross-sectional study was conducted by means of a telephone survey of patients
      shortly after discharge. Patients were asked whether they recalled speaking with
      a pharmacist during their last stay in the hospital. Patients who recalled such
      interactions were asked to rate pharmacy services on a 5-point scale. RESULTS: Of
      1200 patients who were discharged from hospital in June 2007 and who were
      contacted by telephone 2 months later, 400 patients agreed to participate in the
      survey; 3 of these patients were subsequently excluded. Of the 397 respondents
      included in the analysis, 83 (20.9%) recalled speaking to a pharmacist. Most of
      these rated the interaction favourably, with an average satisfaction rating of
      4.4 out of 5. CONCLUSIONS: The Pharmacy Department of the former Calgary Health
      Region now has baseline frequency and satisfaction data for this indicator of
      service value, which can be used as comparators for future assessments of service
      value.

PMID- 22478892
TI  - An instrument to objectively measure pharmacist professionalism as an outcome: a
      pilot study.
AB  - BACKGROUND: Historically, academic success has been a major outcome for
      evaluating the effectiveness of pharmacy education programs and admission
      criteria. In other words, students' overall grades and/or specific course grades
      have determined academic success. However, there is a disconnection between
      students' grades and their performance during practicums or in practice. It was
      postulated that professionalism might be an alternative outcome for measuring
      graduates' abilities. OBJECTIVE: To construct an objective measure of
      professional attitudes and behaviours for recently graduated pharmacists.
      METHODS: A self-report instrument was developed using the American Board of
      Internal Medicine's 6-tenet definition of professionalism. Four months after
      completing the doctor of pharmacy degree (PharmD), pharmacists were asked to
      complete an online version of the professionalism instrument. The Rasch
      Measurement Model (Winsteps, Chicago, Illinois) was used to construct a measure
      from the responses. Using data that fit the model, the Rasch Measurement Model
      can build the interval-level measurements needed for future inferential
      statistical interpretations of ordinal-level data gathered with this instrument.
      RESULTS: Twenty-seven PharmD graduates completed the 15-item instrument. The
      Rasch Measurement Model was used to construct continuous, linear measures of
      pharmacist professionalism from these instrument rating scale data. Most of the
      scales functioned without modification, but 2 of the scales functioned only after
      being collapsed. One person and one item "misfit" the Rasch Measurement Model and
      were omitted from the analysis. After these adjustments, the data fit the model
      well. As a measurement tool, this instrument was overwhelmingly unidimensional;
      the linear model explained 99.9% of the variation in the data using principal
      contrast analysis. Item separation was 3.64 logits, person separation was 2.31
      logits, and reliability was 0.93 by Cronbach's alpha. CONCLUSION: The Rasch
      Measurement Model was used to construct an objective measure of pharmacists'
      professionalism. The results of this pilot project suggest a promising outcome
      measure for evaluating pharmacy graduates soon after completion of university.

PMID- 22478893
TI  - Identifying missed opportunities to curtail antimicrobial therapy for presumed
      ventilator-associated pneumonia using the clinical pulmonary infection score.
AB  - BACKGROUND: Early discontinuation of antimicrobial therapy for ventilator
      associated pneumonia can reduce the emergence of antimicrobial resistance, the
      occurrence of adverse drug events, and the cost of therapy. Evidence suggests
      that discontinuation of therapy by day 3 may be appropriate for patients with a
      clinical pulmonary infection score of 6 or less at baseline and on day 3.
      OBJECTIVES: To determine the proportion of patients eligible for antimicrobial
      discontinuation on day 3 and day 7 of therapy and to determine the proportion of
      eligible patients for whom antimicrobials were discontinued within these
      timeframes. METHODS: A 6-month observational study was conducted from October 3,
      2005, to March 31, 2006, in a 27-bed medical-surgical tertiary care intensive
      care unit. Clinical pharmacists attended daily rounds and prospectively
      identified patients for inclusion in the study. A study pharmacist
      retrospectively calculated clinical pulmonary infection scores. Other data were
      obtained from the quality-improvement database and patient health records for the
      intensive care unit. RESULTS: Ninety-two patients were treated for ventilator
      associated pneumonia during the study period, of whom 49 were included in the
      analysis. At day 3, 17 (35%) of the 49 patients were eligible for early
      discontinuation of antimicrobial therapy, but therapy was discontinued for only 2
      (12%) of these 17 patients. At day 7, 10 (32%) of 31 patients were eligible for
      antimicrobial discontinuation, but therapy was discontinued for only 1 (10%) of
      these 10 patients. CONCLUSIONS: A significant opportunity exists at the authors'
      institution to develop and implement an antimicrobial discontinuation policy that
      uses the clinical pulmonary infection score to guide antimicrobial use for
      patients with ventilator-associated pneumonia.

PMID- 22478894
TI  - Stability of aseptically prepared tazocin solutions in polyvinyl chloride bags.
AB  - BACKGROUND: Tazocin, a mixture of piperacillin and tazobactam, has recently been
      reformulated to include edetate disodium (EDTA) and citric acid. Since the
      introduction of this new formulation, there have been no studies of stability in
      polyvinylchloride (PVC) bags. OBJECTIVE: To complete a physical compatibility and
      chemical stability study of the new formulation of Tazocin, prepared at 2
      concentrations in each of 2 diluents and stored in PVC bags. METHODS: Tazocin, at
      22.5 or 90 mg/mL, was compounded in dextrose 5% in water (D5W) or 0.9% sodium
      chloride (normal saline [NS]) in PVC bags. The bags were stored at 5 degrees C
      with protection from light for 14, 21, or 28 days, followed in each case by
      storage at 23 degrees C with exposure to light for 72 h. Triplicate samples
      collected at each of the 7 time points were analyzed in duplicate using a
      stability-indicating high-performance liquid chromatography method. Physical
      compatibility was determined by monitoring the solutions for changes in colour,
      clarity, and pH. RESULTS: The amount of each drug remaining for each
      concentration in each diluent was above 95% of the initial concentration after
      storage at 5 degrees C with protection from light and above 94% of the initial
      concentration after an additional 72 h at 23 degrees C with exposure to light.
      The pH of the solutions changed only slightly over the course of the study, and
      all solutions remained clear and colourless. CONCLUSIONS: Tazocin solutions at
      22.5 and 90 mg/mL, prepared in PVC bags of either D5W or NS, were chemically
      stable after storage for up to 28 days at 5 degrees C with protection from light
      followed by 72 h at 23 degrees C with exposure to light.

PMID- 22478895
TI  - Reimbursement for supportive cancer medications through private insurance in
      Saskatchewan.
AB  - BACKGROUND: As demand for cancer treatment grows, and newer, more expensive drugs
      become available, public payers in Canada are finding it increasingly difficult
      to fund the full range of available cancer drugs. OBJECTIVE: To determine the
      extent of private drug coverage for supportive cancer treatments in Saskatchewan,
      preparatory to exploring the potential for cost-sharing. METHODS: Patients who
      presented for chemotherapy and who provided informed consent for participation
      were surveyed regarding their access to private insurance. Insurers were
      contacted to verify patients' level of coverage for supportive cancer
      medications. Groups with specified types of insurance were compared statistically
      in terms of age, income bracket, time required to assess insurance status, and
      amount of deductible. Logistic regression was used to determine the effect of
      patients' age and income on the probability of having insurance. RESULTS: Of 169
      patients approached to participate, 156 provided consent and completed the
      survey. Their mean age was 58.5 years. About two-fifths of all patients (64 or
      41%) were in the lowest income bracket (up to $30 000). Sixty-three (40%) of the
      patients had private insurance for drugs, and 36 (57%) of these plans included
      reimbursement for supportive cancer medications. A deductible was in effect in 31
      (49%) of the plans, a copayment in 28 (44%), and a maximum payment in 8 (13%).
      Income over $50 000 was a significant predictor of access to drug insurance (p =
      0.003), but age was not significantly related to insurance status. CONCLUSIONS: A
      substantial proportion of cancer patients in this study had access to private
      insurance for supportive cancer drugs for which reimbursement is currently
      provided by the Saskatchewan Cancer Agency. Cost-sharing and optimal utilization
      of the multipayer environment might offer a greater opportunity for public payers
      to cover future innovative and supportive therapies for cancer, but further study
      is required to determine whether a cost-sharing program would be cost-effective
      and in the best interest of patients.

PMID- 22478896
TI  - Medication reconciliation by a pharmacist in the emergency department: a pilot
      project.

PMID- 22478898
TI  - Role 3 multinational medical unit kandahar air field, afghanistan.

PMID- 22478897
TI  - Practice spotlight: community intravenous program, winnipeg regional health
      authority.

PMID- 22478899
TI  - Fatal outcome after inadvertent injection of epinephrine intended for topical
      use.

PMID- 22478900
TI  - Should the Window for Intravenous Administration of Tissue Plasminogen Activator
      in the Treatment of Acute Ischemic Stroke be Extended to 4.5 Hours?

PMID- 22478901
TI  - Failure of spinal anesthesia with marcaine (bupivacaine): recent cluster of
      cases.

PMID- 22478902
TI  - Ready, set ... go!

PMID- 22478903
TI  - "I hear and I forget, I see and I remember, I do and I understand".

PMID- 22478904
TI  - Holy family hospital vancouver, british columbia.

PMID- 22478905
TI  - Potentially inappropriate prescribing of benzodiazepines for older adults and
      risk of falls during a hospital stay: a descriptive study.
AB  - BACKGROUND: Falls have been identified as a potential adverse event associated
      with the administration of psychotropic medications to older patients. OBJECTIVE:
      The objective of this exploratory study was to examine the association between
      potentially inappropriate prescribing of benzodiazepines, as defined by the Beers
      criteria, by older adults (at least 65 years of age) and the risk of having a
      fall during acute inpatient care. METHODS: This 1-year retrospective cross
      sectional study of discharges from a tertiary care hospital in Halifax, Nova
      Scotia, used pharmacy data to identify the prescription of benzodiazepines listed
      in the updated Beers criteria as being associated with an increased risk of
      falls. These data were linked with information on in-hospital falls from
      occurrence report forms. RESULTS: For 5831 (58.1%) of the 10 044 discharges, the
      patient had received a prescription for at least one benzodiazepine during the
      hospital stay. A total of 574 falls were reported (for 374 patients), and 226
      (39.4%) of the falls resulted in an injury. According to the Beers criteria, for
      936 (9.3%) of the discharges, the patient had received a prescription for at
      least one potentially inappropriate benzodiazepine. However, there was no
      statistically significant difference between patients with a prescription for a
      potentially inappropriate benzodiazepine and those receiving an appropriate or no
      benzodiazepine in terms of occurrence of falls (4.5% versus 3.8%, p = 0.30) or
      fall-related injuries (2.6% versus 1.8%, p = 0.08). The median length of stay was
      about 3 days longer for the former group (9 versus 6 days, p < 0.001).
      CONCLUSIONS: The findings from the current study do not support use of the Beers
      criteria related to benzodiazepines alone for identifying patients at risk of
      falls or injuries.

PMID- 22478906
TI  - Unintended medication discrepancies associated with reliance on prescription
      databases for medication reconciliation on admission to a general medical ward.
AB  - BACKGROUND: In a recent study, 50% of the patients who were admitted to a
      hospital's general medicine ward had at least one error in medication orders at
      the time of admission related to inaccuracies in the medication history. The use
      of computerized prescription databases has been suggested as a way to improve
      medication reconciliation at the time of admission. OBJECTIVE: To quantify and
      describe unintended discrepancies between a best possible medication history and
      medications ordered on admission to the general medicine ward in a hospital with
      routine access to a provincial outpatient prescription database (British
      Columbia's PharmaNet). METHODS: This prospective study involved 20 patients who
      were regularly using at least 4 prescription medications before admission to
      hospital. The best possible medication history for each patient (based on a
      review of the medical chart and the PharmaNet record and an interview with the
      patient) was compared with the physician's admission orders to identify any
      discrepancies. The frequency and perceived severity of discrepancies, graded
      independently by 3 physicians, were compared with observations from a similar
      study conducted at a hospital where a prescription database was not available.
      RESULTS: The 20 patients were recruited between September 2005 and January 2006.
      For 8 patients (40%), information in the PharmaNet database was consistent with
      the prescription medication list obtained during the best possible medication
      history at the time of admission. For the other 12 patients, a total of 30
      unintended discrepancies were identified, 13 (43%) of which were classified as
      having potential for moderate or severe harm. The proportion of patients with
      unintended discrepancies was similar to that for the comparison cohort (60%
      versus 54%). Although the percentage of discrepancies involving omissions was
      lower than in the comparison population (37% versus 46%), these results were
      offset by a higher proportion of commission discrepancies (27% versus 0%).
      CONCLUSION: Unintended discrepancies were frequent, despite use of the PharmaNet
      database at the time of admission. Inconsistencies between the PharmaNet record
      and patients' actual medication use, coupled with failure to verify PharmaNet
      data with patients, were likely contributing factors.

PMID- 22478907
TI  - Clinical experience with argatroban for heparin-induced thrombocytopenia in a
      large teaching hospital.
AB  - BACKGROUND: Argatroban is a direct thrombin inhibitor approved for the
      prophylaxis or treatment of thrombosis in patients with heparin-induced
      thrombocytopenia (HIT). The product monograph does not guide clinicians beyond
      specifying the initial dose of 2 MUg/kg per minute (or 0.5 MUg/kg per minute for
      patients with hepatic impairment). Some authors have suggested that in the
      intensive care unit (ICU) and for patients with acute cardiac disease and those
      with renal or hepatic dysfunction, this dose may result in a supratherapeutic
      activated partial thromboplastin time (aPTT). OBJECTIVES: To evaluate the
      efficacy and safety of argatroban in adult patients with suspected HIT in a large
      teaching hospital, and to review dosing for patients in the ICU, patients with
      acute cardiac disease, and patients with renal or hepatic dysfunction. METHODS:
      Charts of patients with suspected HIT who had received argatroban for at least 24
      h between October 1, 2005, and October 1, 2007, at the Foothills Medical Centre,
      Calgary, Alberta, were examined retrospectively. RESULTS: Thirty patients met the
      inclusion criteria, with charts available for review. Of these, 21 (70%) patients
      had an initial argatroban dose of 2 MUg/kg per minute and 4 (13%) had an initial
      dose of 0.5 MUg/kg per minute. The median duration of therapy was 6 days, and the
      mean dose was 2.14 MUg/kg per minute. There were 122 dosage adjustments, the most
      common change being 0.5 MUg/kg per minute, followed by adjustments of 1 and 0.1
      MUg/kg per minute. Six patients had supratherapeutic aPTT values (above 100 s),
      and none experienced major bleeding. CONCLUSIONS: The results of this study
      suggest that an initial argatroban dose of 2 MUg/kg per minute is appropriate for
      patients with no hepatic dysfunction. Patients with acute cardiac disease and
      critically ill patients may require lower doses of argatroban; however no dosage
      adjustments are required for patients with renal dysfunction.

PMID- 22478908
TI  - Inventory of drug samples in a health care institution.
AB  - BACKGROUND: Few data exist on the presence of drug samples in health care
      facilities. Although the use of drug samples has potential benefits, this
      practice is also controversial, as it can contribute to non-optimal drug use. The
      objective of this study was to evaluate the inventory of drug samples in a health
      care institution and to determine compliance with existing policies and
      procedures. METHODS: This descriptive observational study was conducted in a
      university hospital centre from October 18 to November 1, 2007. A standardized
      data collection form was used for a physical inventory, which was intended to
      identify all drug samples available in the institution. The following information
      was recorded: number of locations where drug samples were found, primary patient
      care activity performed at each location, number of storage areas in the
      location, type of storage, presence of a lock, location of the key (if a lock was
      present), medical specialty, number of physicians and nurses likely to use the
      samples, reasons given for handing out samples, presence of a designated person
      to manage the samples, physical inventory (i.e., various details for each
      distribution unit), and declaration of samples to the pharmacy department. The
      inventory was conducted by 2 research assistants during day shifts. RESULTS: A
      total of 84 locations were included in the inventory, and drug samples were found
      in 21 locations (with a total of 31 storage areas). All of the locations were
      intended for ambulatory patients (outpatient clinics and day centres). No drug
      samples were found in inpatient care units. The drug samples, which came from 62
      different pharmaceutical companies, represented a total of 159 generic entities
      and 266 different brands. Of the distribution units for drug samples that were
      identified during this inventory, 59% were not on the hospital's local formulary.
      Furthermore, only 3.5% of the distribution units had been declared to the
      pharmacy department, in accordance with established policy. The sample
      distribution units, including expired units, totalled 78 955 doses, with a total
      value of Can$48 783 (based on unit prices in effect in October 2007). CONCLUSION:
      This study presents an inventory of drug samples in an urban health care
      institution and reports compliance with the institution's policies and procedures
      regarding drug samples. Samples were found only in outpatient clinics and
      represented 2.4 times the hospital's floor stock of medications. Most of the
      samples inventoried were not listed on the hospital's formulary. It appears that
      the use of drug samples is underestimated in hospital settings. Further studies
      are needed to evaluate the importance of drug samples and the risks associated
      with their use.

PMID- 22478909
TI  - Evaluating the Risk of Re-identification of Patients from Hospital Prescription
      Records.
AB  - BACKGROUND: Pharmacies often provide prescription records to private research
      firms, on the assumption that these records are de-identified (i.e., identifying
      information has been removed). However, concerns have been expressed about the
      potential that patients can be re-identified from such records. Recently, a large
      private research firm requested prescription records from the Children's Hospital
      of Eastern Ontario (CHEO), as part of a larger effort to develop a database of
      hospital prescription records across Canada. OBJECTIVE: To evaluate the ability
      to re-identify patients from CHEO'S prescription records and to determine ways to
      appropriately de-identify the data if the risk was too high. METHODS: The risk of
      re-identification was assessed for 18 months' worth of prescription data. De
      identification algorithms were developed to reduce the risk to an acceptable
      level while maintaining the quality of the data. RESULTS: The probability of
      patients being re-identified from the original variables and data set requested
      by the private research firm was deemed quite high. A new de-identified record
      layout was developed, which had an acceptable level of re-identification risk.
      The new approach involved replacing the admission and discharge dates with the
      quarter and year of admission and the length of stay in days, reporting the
      patient's age in weeks, and including only the first character of the patient's
      postal code. Additional requirements were included in the data-sharing agreement
      with the private research firm (e.g., audit requirements and a protocol for
      notification of a breach of privacy). CONCLUSIONS: Without a formal analysis of
      the risk of re-identification, assurances of data anonymity may not be accurate.
      A formal risk analysis at one hospital produced a clinically relevant data set
      that also protects patient privacy and allows the hospital pharmacy to explicitly
      manage the risks of breach of patient privacy.

PMID- 22478911
TI  - Practice Spotlight: Interdisciplinary HIV Outpatient Clinic.

PMID- 22478910
TI  - Structuring an early clinical experience for pharmacy students: lessons learned
      from the hospital perspective.

PMID- 22478912
TI  - Pharmaceutical bar coding: moving forward in Canada.

PMID- 22478913
TI  - Is it ethical for health care organizations to charge institutions for
      experiential rotations?

PMID- 22478914
TI  - CSHP Summer Educational Sessions (SES) 2009: Poster Abstracts / Seances
      educatives d'ete (SEE) 2009 de la SCPH : Resumes des affiches.

PMID- 22478915
TI  - The professor is in.

PMID- 22478916
TI  - Overcoming barriers to adoption of guidelines and use of proven interventions: it
      is my table!

PMID- 22478917
TI  - Drug-related problems in patients undergoing elective total joint arthroplasty of
      the hip or knee.
AB  - BACKGROUND: Few studies have evaluated drug-related problems in patients
      undergoing elective total hip or knee arthroplasty. OBJECTIVE: To quantify, for
      patients undergoing elective total joint arthroplasty, drug-related problems
      arising from medication orders written before or immediately after the surgery.
      The primary outcome was the proportion of patients with at least one drug-related
      problem. The secondary outcomes were the total number and descriptions of these
      problems, according to the patient's age and the category, type, and severity of
      the drug-related problem. METHODS: From among patients who underwent elective
      total joint arthroplasty in a large Canadian regional health authority in 2005,
      150 were randomly selected for this chart audit. Patients were included if they
      had been taking more than one medication before surgery. The charts were examined
      for drug-related problems, which were categorized according to whether the
      problem involved a prescription for a home medication, an order for a
      postoperative medication, or a potential indication for drug therapy. The
      problems were further described by type and potential severity. RESULTS: Of the
      146 patients whose charts were available, 116 (79.5%) had at least one drug
      related problem, with a mean of 1.88 drug-related problems per patient. Of the
      146 patients, 88 (60.3%) had at least one drug-related problem involving a home
      medication, 34 (23.3%) had problems related to postoperative orders, and 37
      (25.3%) had problems related to a potential indication. The mean number of drug
      related problems per patient was 2.03 for those 65 years of age or older and 1.56
      for those younger than 65 years (p = 0.09); however, more of the older patients
      experienced at least one drug-related problem related to home medications (67%
      [67/100] versus 46% [21/46], p = 0.02). The most common types of problems were
      medication omissions, illegible drug orders, inappropriate dose or frequency, and
      drug-allergy interactions. Of the 275 drug-related problems identified, 147
      (53.5%) were deemed potentially harmful, 78 (28.4%) required monitoring, and 50
      (18.2%) were considered not harmful. CONCLUSIONS: In this study, patients who
      underwent total joint arthroplasty experienced many drug-related problems.
      Pharmacists may have opportunities to optimize patient care by identifying,
      resolving, and preventing drug-related problems in this patient population.

PMID- 22478918
TI  - Treatment dosing of low-molecular-weight heparins and the dose cap dilemma:
      considerations for patients in Canada.
AB  - BACKGROUND: In Canada, there is a dose cap for weight-based treatment with low
      molecular-weight (LMW) heparins. OBJECTIVE: To review whether capping of LMW
      heparin doses is warranted for patients with obesity. METHODS: English-language
      publications concerning the use of LMW heparin in Canada were reviewed, and the
      literature regarding use of these drugs at treatment doses in patients with
      obesity was assessed. RESULTS: Five pharmacokinetic or pharmacodynamic studies
      meeting the inclusion criteria were identified. The evidence in those studies
      pointed toward no excess accumulation of LMW heparin in patients with obesity. In
      addition, 5 trials involving patients with acute coronary syndromes and 6 trials
      involving patients with venous thromboembolism and other indications were
      identified, but only 7 of these 11 trials included sufficient information for
      review. Subgroup analysis of patients with acute coronary syndrome whose LMW
      heparin dose was not capped showed no increased risk of bleeding for obese
      patients treated with enoxaparin. For patients with venous thromboembolism and
      other indications, the best evidence was for dalteparin, with anti-Xa levels used
      as a surrogate end point. In this setting, excess accumulation did not occur when
      there was no dose cap. DISCUSSION: There is little literature dedicated to the
      dosing of LMW heparin for obese patients. In particular, there are few data for
      those with body weight above 150 kg. Despite the limitations of these studies,
      there appears to be little justification for capping the doses of these drugs. On
      the basis of the available literature, it is suggested that treatment doses of
      LMW heparin be based on body weight up to 150 kg.

PMID- 22478919
TI  - Buffered lidocaine hydrochloride solution with and without epinephrine: stability
      in polypropylene syringes.
AB  - BACKGROUND: Pain associated with infiltrating the skin with lidocaine can be
      reduced by buffering the solution with sodium bicarbonate. OBJECTIVES: To
      determine the physical compatibility and chemical stability of lidocaine
      hydrochloride solution buffered with 8.4% sodium bicarbonate, with and without
      epinephrine, packaged in polypropylene syringes and stored at 5 degrees C with
      protection from light. METHODS: Lidocaine solutions (1% and 2%), with and without
      epinephrine 1:100 000, were diluted 10:1 with 8.4% sodium bicarbonate, packaged
      in 3-mL polypropylene syringes, and stored at 5 degrees C (range 3 degrees C to 8
      degrees C). On each of days 0, 3, 7, 10, 14, 17, 21, 24, and 28, the contents of
      3 syringes for each solution of lidocaine combined with epinephrine were
      collected separately in glass vials and frozen at -70 degrees C for subsequent
      analysis. In addition, on days 0, 7, 14, 21, and 28, the contents of 3 syringes
      for each lidocaine solution without epinephrine were collected separately in
      glass vials and frozen at -70 degrees C for subsequent analysis. Chemical
      stability was determined with a validated, stability-indicating high-performance
      liquid chromatography method. Changes in colour, clarity, and pH were used to
      determine physical compatibility of the solutions. RESULTS: All buffered
      lidocaine solutions containing epinephrine (1:100 000) retained at least 93.3% of
      the original concentration of epinephrine and 97.5% of the lidocaine
      concentration for 7 days when stored at 5 degrees C with protection from light.
      In contrast, the epinephrine-free solutions retained at least 94.7% of the
      initial concentration of lidocaine for the duration of the study (28 days). All
      samples remained clear, colourless, and free of precipitate throughout the study,
      and there were no significant changes in pH. CONCLUSION: Extemporaneously
      prepared buffered lidocaine (1% and 2%) packaged in polypropylene syringes
      remained stable for up to 28 days when properly refrigerated with protection from
      light. A 7-day expiry date was established for buffered lidocaine solutions
      containing epinephrine, packaged in polypropylene syringes, and stored with
      refrigeration and protection from light.

PMID- 22478920
TI  - Reasons for Non-use of Proven Interventions for Hospital Inpatients: Pharmacists'
      Perspectives.
AB  - BACKGROUND: Recently, health care institutions have been using performance
      indicators to measure and improve quality of care. One such indicator, the Ideal
      Medication Intervention Index, reflects the rate of implementation of proven
      pharmacologic interventions, which studies have shown are underutilized.
      Identifying the reasons why proven interventions are underused is essential to
      determining how their rate of use can be improved. OBJECTIVE: To characterize the
      reasons for non-use of proven interventions from the perspective of clinical
      pharmacists within the authors' health care organization. METHODS: A survey of
      all clinical pharmacists within the organization was conducted. The survey used
      standardized, case-based scenarios involving pharmacologic interventions known to
      improve health outcomes. Respondents were asked to rank potential reasons why a
      patient might not receive a proven intervention. RESULTS: Of the 115 pharmacists
      invited, 53 (46%) participated in the survey. Most of the respondents practised
      on medical wards. The 2 most common reasons for non-use of proven interventions
      were a team preference to defer management of such issues to the outpatient care
      provider and issues related to workload. CONCLUSIONS: Clinical pharmacists
      revealed that their perceptions of priorities, communication with their
      interdisciplinary teams, and workload issues contributed to non-use of proven
      pharmacologic interventions among patients in their care. Efforts to increase the
      utilization of the proven clinical interventions studied here should focus on
      changing pharmacists' perceptions of priorities.

PMID- 22478921
TI  - Best possible medication history for hemodialysis patients obtained by a pharmacy
      technician.
AB  - BACKGROUND: Outpatients undergoing hemodialysis are at high risk for adverse drug
      events. Limited resources make it challenging for pharmacists to routinely obtain
      a best possible medication history (BPMH). OBJECTIVES: The primary objective was
      to determine whether, for patients undergoing hemodialysis, a pharmacy technician
      has the skills to obtain a BPMH that would allow a pharmacist to identify drug
      related problems. The secondary objectives were to determine the number and types
      of medication discrepancies and drug-related problems identified and the time
      required by the technician to complete the BPMH. METHODS: All patients treated in
      the hemodialysis unit during the study period were included, except for those who
      required an interpreter or were unable to participate in an in-person interview.
      A single technician was taught how to interview patients according to a
      structured format. For each patient, the technician's BMPH was verified by a
      pharmacist. The agreement rate between technician and pharmacists was determined,
      along with the number and types of discrepancies and drug-related problems
      identified. RESULTS: The technician interviewed 99 patients. Of the 1334
      medication orders reviewed, the technician and pharmacists agreed on all but 15
      (agreement rate 98.9%). A total of 358 medication discrepancies were noted for 93
      patients (3.8 discrepancies per patient). Of these, 210 (59%) were undocumented
      intentional discrepancies, and 148 (41%) were unintentional discrepancies (most
      commonly errors of commission). Of the 135 drug-related problems identified, the
      majority involved dosing problems or nonadherence. The technician required an
      average of 17 min for each interview. CONCLUSION: An adequately trained
      technician was capable of interviewing patients to create a BPMH. A variety of
      medication discrepancies and drug-related problems were identified. Generation of
      a BPMH by a technician is a useful approach allowing pharmacists to identify drug
      related problems.

PMID- 22478922
TI  - Limited-sampling strategies for anti-infective agents: systematic review.
AB  - BACKGROUND: Area under the concentration-time curve (AUC) is a pharmacokinetic
      parameter that represents overall exposure to a drug. For selected anti-infective
      agents, pharmacokinetic-pharmacodynamic parameters, such as AUC/MIC (where MIC is
      the minimal inhibitory concentration), have been correlated with outcome in a few
      studies. A limited-sampling strategy may be used to estimate pharmacokinetic
      parameters such as AUC, without the frequent, costly, and inconvenient blood
      sampling that would be required to directly calculate the AUC. OBJECTIVE: To
      discuss, by means of a systematic review, the strengths, limitations, and
      clinical implications of published studies involving a limited-sampling strategy
      for anti-infective agents and to propose improvements in methodology for future
      studies. METHODS: The PubMed and EMBASE databases were searched using the terms
      "anti-infective agents", "limited sampling", "optimal sampling", "sparse
      sampling", "AUC monitoring", "abbreviated AUC", "abbreviated sampling", and
      "Bayesian". The reference lists of retrieved articles were searched manually.
      Included studies were classified according to modified criteria from the US
      Preventive Services Task Force. RESULTS: Twenty studies met the inclusion
      criteria. Six of the studies (involving didanosine, zidovudine, nevirapine,
      ciprofloxacin, efavirenz, and nelfinavir) were classified as providing level I
      evidence, 4 studies (involving vancomycin, didanosine, lamivudine, and lopinavir
      ritonavir) provided level II-1 evidence, 2 studies (involving saquinavir and
      ceftazidime) provided level II-2 evidence, and 8 studies (involving
      ciprofloxacin, nelfinavir, vancomycin, ceftazidime, ganciclovir, pyrazinamide,
      meropenem, and alpha interferon) provided level III evidence. All of the studies
      providing level I evidence used prospectively collected data and proper
      validation procedures with separate, randomly selected index and validation
      groups. However, most of the included studies did not provide an adequate
      description of the methods or the characteristics of included patients, which
      limited their generalizability. CONCLUSIONS: Many limited-sampling strategies
      have been developed for anti-infective agents that do not have a clearly
      established link between AUC and clinical outcomes in humans. Future studies
      should first determine if there is an association between AUC monitoring and
      clinical outcomes. Thereafter, it may be worthwhile to prospectively develop and
      validate a limited-sampling strategy for the particular anti-infective agent in a
      similar population.

PMID- 22478923
TI  - Best possible medication history by a pharmacy technician at a tertiary care
      hospital.

PMID- 22478924
TI  - [Not Available].

PMID- 22478925
TI  - Practice spotlight: dawn dalen.

PMID- 22478926
TI  - Prograf and Advagraf Mix-up.

PMID- 22478928
TI  - Ross memorial hospital, lindsay, ontario.

PMID- 22478927
TI  - Should the provincial colleges of pharmacy create a category for "advanced
      practice pharmacist"?

PMID- 22478929
TI  - Resident-on-call service.

PMID- 22478930
TI  - A Commitment to Act: CSHP 2015 and the Blueprint for Pharmacy.

PMID- 22478931
TI  - Integrity in authorship and publication.

PMID- 22478932
TI  - Evaluation of 2 weight-based protocols for administration of heparin.
AB  - BACKGROUND: In 1996, a weight-based protocol for administration of heparin was
      implemented and assessed at the authors' institution. Since then, several
      modifications have been made, including introduction of a lower-target protocol.
      These changes warranted re-evaluation of the standard and lower-target protocols.
      OBJECTIVE: To determine and compare the efficacy and safety of the standard and
      lower-target protocols for heparin administration and to descriptively compare
      these findings with the original 1996 protocol. METHODS: This 5-month
      retrospective, observational study involved 100 consecutive patients, 50 assigned
      to each of the 2 current protocols (standard and lower target), who were treated
      between September 2006 and January 2007. The primary outcomes were efficacy,
      represented by the time to achieve partial thromboplastin time (PTT) above the
      lower limit of the therapeutic range and within the therapeutic range, and
      safety, as indicated by the incidence of major bleeding and thromboembolic events
      over the entire course of heparin therapy. RESULTS: There were no significant
      differences between the standard and lower-target protocols with respect to
      median time to achieve PTT above the lower limit of the therapeutic range (6.0 h
      versus 6.3 h, respectively; p = 0.24) or median time to achieve PTT within the
      therapeutic range (14.4 h versus 14.3 h, respectively; p = 0.93). Compared with
      the original 1996 protocol, these protocols appeared to have shorter times to
      achieve both of these outcomes. The rate of adverse events was infrequent, with
      fewer episodes of major bleeding (1%, for both current protocols combined) than
      in the 1996 study (10%). CONCLUSIONS: The 2 current weight-based protocols for
      administration of heparin appeared to have similar efficacy and safety and
      appeared to perform at least as well as the original 1996 protocol.

PMID- 22478933
TI  - Dosing Recommendations for Continuous Venovenous Hemodiafiltration with AN69
      Filter Membranes and Prismaflex Dialyzers.
AB  - BACKGROUND: Continuous renal replacement therapy is used to manage fluid and
      solute imbalances in critically ill patients but may affect the clearance of
      concurrently administered drugs. The impact of continuous renal replacement
      therapy on pharmacokinetics has been summarized, but previous reports have
      included studies involving various modes of therapy, filter membranes, and brands
      of dialyzers, which makes it difficult to apply the recommendations to individual
      patients. In Canada, continuous venovenous hemodiafiltration (CVVHDF) with a
      Prismaflex dialyzer machine (Gambro, Saint-Leonard, Quebec) and AN69 filter
      membranes is the most common mode of continuous renal replacement therapy for
      critically ill patients. OBJECTIVE: To develop a set of dosage recommendations
      for commonly encountered medications used in treating critically ill patients who
      are undergoing CVVHDF with a Prismaflex dialyzer and AN69 filter membranes.
      METHODS: A literature search was conducted to identify studies of the
      pharmacokinetics and disposition of drugs in patients undergoing CVVHDF via a
      Prismaflex dialyzer (sold under 3 brand names: Gambro, Hospal, and Prima)
      equipped with polyacrylonitrile (AN69) filter membranes. From each study, the
      mean total clearance of each study medication during CVVHDF was extracted and
      compared with clearance of the drug in patients not undergoing CVVHDF, to produce
      dosage guidelines for patients undergoing CVVHDF. RESULTS: A total of 22 studies
      of 14 medications were included in the final review. For most of the drugs, the
      total clearance during CVVHDF was less than clearance in patients whose renal
      function was presumed to be normal. Fluconazole and moxifloxacin had greater
      total clearance during CVVHDF, but a dose adjustment during CVVHDF was deemed
      necessary only for fluconazole. CONCLUSIONS: Dosing recommendations were created
      for concurrently administered drugs for patients undergoing treatment with this
      particular CVVHDF equipment. Patient-specific factors and clinical judgement
      should also be taken into account.

PMID- 22478934
TI  - Stability of celecoxib oral suspension.
AB  - BACKGROUND: Celecoxib is a selective cyclo-oxygenase 2 inhibitor that relieves
      pain without affecting platelet function, causing gastrointestinal toxic effects,
      or increasing the risk of bleeding. OBJECTIVES: To develop a suspension
      formulation for oral celecoxib and to determine its physical and chemical
      stability when packaged in amber polyvinyl chloride (PVC) bottles and stored with
      refrigeration (5 degrees C) and at room temperature (23 degrees C). METHODS: The
      contents of celecoxib capsules were used to prepare a single suspension, with Ora
      Blend used as the suspending and flavouring agent. The suspension (10 mg/mL) was
      then packaged in amber PVC bottles and stored at either 5 degrees C or 23 degrees
      C. Samples were collected on days 0, 7, 14, 21, 27, 56, and 93. Chemical
      stability was determined using a validated stability-indicating high-performance
      liquid chromatography method. At each sampling time, the suspensions were checked
      visually for changes in appearance (i.e., colour, layering, caking, and ease of
      resuspension), odour, and pH. RESULTS: All of the suspensions were stable for at
      least 93 days, regardless of storage conditions. There were no apparent changes
      in physical appearance, nor were there any substantial changes in odour or pH.
      CONCLUSIONS: Suspensions of celecoxib (10 mg/mL in Ora-Blend) packaged in amber
      PVC bottles were stable for up to 93 days when stored at 5 degrees C or 23
      degrees C. A 3-month expiry date has been established for this oral suspension on
      the basis of physical compatibility and chemical stability.

PMID- 22478936
TI  - Survey of Canadian Pharmacists' Responses to Warnings of Potential Interactions
      Between Ceftriaxone and Calcium in IV Solutions.
AB  - BACKGROUND: In 2007, because of a potential interaction between ceftriaxone and
      calcium-containing IV solutions, Roche Laboratories (manufacturer of Rocephin
      [ceftriaxone] in the United States) issued letters to health care professionals
      advising them of changes to the product monograph. Subsequently, warning letters
      were also issued by the US Food and Drug Administration (FDA) and Health Canada.
      The Health Canada recommendations and their implications for clinical practice
      generated debate in the Canadian hospital pharmacy community. OBJECTIVE: To
      evaluate the response to the warnings among hospital pharmacists and their
      respective institutions. METHODS: An anonymous, voluntary 10-question survey was
      distributed to members of the Pharmacy Specialty Networks of the Canadian Society
      of Hospital Pharmacists. Requests to participate were solicited via 2 e-mail
      messages. Responses were analyzed descriptively. RESULTS: A total of 152
      pharmacists participated in the survey. Forty-three respondents (28.3%) reported
      being very concerned and 86 (56.6%) reported being somewhat concerned about the
      Health Canada Notice to Hospitals. About half (77/152 [50.7%]) of the respondents
      felt that the Health Canada notice did not need to be strictly heeded. Two-thirds
      (98/145 [67.6%]) reported that their institutions had addressed the risk of an
      interaction through a change in policy regarding the administration of
      ceftriaxone. Eighty-eight (61.5%) of 143 participants indicated that their
      institution's official position on the notice was that it represented a "relative
      contraindication" (i.e., the benefit may outweigh the risk). CONCLUSIONS: Warning
      letters issued by the manufacturer, the FDA, and Health Canada generated concern
      within the Canadian hospital pharmacy community. However, a large proportion of
      hospital pharmacy practitioners did not agree with strict adherence to the Health
      Canada notice.

PMID- 22478935
TI  - Role of therapeutic drug monitoring of voriconazole in the treatment of invasive
      fungal infections.
AB  - BACKGROUND: Voriconazole is a broad-spectrum, second-generation triazole
      antifungal agent with demonstrated efficacy in the treatment of invasive fungal
      infections caused by Aspergillus spp. and Candida spp. Given the
      characteristically poor prognosis of patients with invasive fungal infections and
      the protracted duration of treatment required, therapeutic monitoring of
      voriconazole is, in theory, an attractive method to optimize antifungal therapy.
      OBJECTIVE: To determine the utility of therapeutic drug monitoring for
      voriconazole. METHODS: A previously published decision-making algorithm was used
      to assess the currently available literature on therapeutic drug monitoring of
      voriconazole. RESULTS: Several analytical methods can be used to quantify plasma
      or serum concentrations of voriconazole. Reasons for therapeutic monitoring of
      this drug include wide variability both within and between individuals secondary
      to drug properties, drug-drug interactions, and disease states. Furthermore,
      voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance.
      Another potential factor in favour of therapeutic drug monitoring for
      voriconazole is genetic polymorphism of CYP2C19, whereby patients who are
      homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold
      greater exposure to voriconazole. The concentrations of this drug are also
      greater in patients with hepatic impairment. Drug-drug interactions with other
      substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole
      concentrations. However, the correlations between plasma concentrations of
      voriconazole and its efficacy and toxicity are not well defined. Although lower
      and upper target thresholds of 0.25-2 mg/L and 4-6 mg/L, respectively, have been
      suggested, studies to date have not been appropriately designed or powered to
      reveal any definitive association. CONCLUSIONS: Routine therapeutic drug
      monitoring of voriconazole is not recommended except in certain circumstances,
      such as lack of response to therapy or evidence of toxicity, in which case
      selective monitoring of voriconazole concentrations may be of clinical utility.

PMID- 22478937
TI  - Development of a simplified protocol for administration of 20% magnesium sulphate
      for prophylaxis and treatment of eclampsia.
AB  - BACKGROUND: Magnesium sulphate is a high-risk medication that is used extensively
      for prophylaxis and treatment of eclampsia. To accommodate recommendations
      related to fluid restrictions and patient safety, a protocol was developed for
      the administration of 20% magnesium sulphate. OBJECTIVES: To determine whether
      administration of 20% magnesium sulphate increased the risk of phlebitis relative
      to 2% to 8% magnesium sulphate solutions, to determine if the institution's
      protocol for administration of 20% magnesium sulphate reduced errors during
      administration, and to identify strategies to further reduce potential errors.
      METHODS: A retrospective chart audit was undertaken for patients who had received
      magnesium sulphate for prophylaxis of eclampsia from December 2004 to December
      2007. A failure mode and effect analysis was used to identify additional safety
      strategies. RESULTS: A total of 47 patients received magnesium sulphate according
      to the old administration protocol (2% to 8% solution) and 29 according to the
      new protocol (20% solution). No evidence of phlebitis was documented for any of
      these 76 patients. A few errors occurred with changes in rates or concentrations
      and because of failure to reset the pump after the loading dose, but there was no
      documented harm to any of the patients. Strategies to further reduce errors in
      the administration of magnesium sulphate included development of preprinted
      orders, use of 20% magnesium sulphate for all infusion rates, changes to pump
      settings to enable use of fractional infusion rates, preparation of magnesium
      sulphate in mini-bags in the pharmacy, double-check of pump settings by nurses,
      anesthesiology consult, and distribution of protocols to all areas in the
      hospital (to limit errors associated with patient transfers). CONCLUSIONS: There
      was no documented phlebitis, and fewer errors occurred when 20% magnesium
      sulphate was used. Several additional strategies were identified to reduce errors
      in the administration of this high-risk medication.

PMID- 22478938
TI  - Pulmonary Infection Due to Mycobacterium malmoense in a Patient with Crohn
      Disease.

PMID- 22478939
TI  - Antiretroviral therapeutic drug monitoring in Canada: current status and
      recommendations for clinical practice.

PMID- 22478940
TI  - Practice spotlight: a telepharmacy model of care for hospitals.

PMID- 22478941
TI  - Hospital-acquired acute hyponatremia and parenteral fluid administration in
      children.

PMID- 22478943
TI  - East kootenay regional hospital, cranbrook, british columbia.

PMID- 22478942
TI  - Do automated dispensing machines improve patient safety?

PMID- 22478945
TI  - In every challenge there lies opportunity: rise of the phoenix.

PMID- 22478944
TI  - Does prolonged infusion allow lower daily dose of meropenem than bolus dosing?

PMID- 22478946
TI  - Do not accept the status quo!

PMID- 22478947
TI  - Appropriateness of adrenocorticotropic hormone stimulation test for critically
      ill patients.
AB  - BACKGROUND: In earlier work, it was shown that patients with septic shock who
      also have adrenal insufficiency experience a benefit in terms of lower mortality
      rates with hydrocortisone supplementation. As such, the adrenocorticotropic
      hormone (ACTH) stimulation test has been used frequently to identify these
      patients. However, recent evidence has suggested that the identification and
      treatment of adrenal insufficiency in patients with septic shock does not reduce
      mortality. These results call into question the utility of the ACTH stimulation
      test in this patient population. OBJECTIVES: To determine the indications for
      ordering the ACTH stimulation test for critically ill patients at a tertiary care
      hospital and to classify the indications as either appropriate (e.g., primary
      adrenal insufficiency or medication-induced suppression of the hypothalamus
      pituitary-adrenal axis) or inappropriate (e.g., patients with septic shock, prior
      etomidate exposure, or absence of steroid use). METHODS: A retrospective analysis
      of health care records was conducted for all patients who had been admitted to
      the intensive care unit and who had undergone an ACTH stimulation test during
      2007. For each patient, the indication for the test was identified and classified
      as appropriate or inappropriate. RESULTS: A total of 35 ACTH stimulation tests
      were performed during the study period, of which 8 (23%) were classified as
      having an appropriate indication and 27 (77%) as having an inappropriate
      indication. Of the tests with an inappropriate indication, 15 (56%) were ordered
      for patients with septic shock. However, the number of ACTH tests ordered for
      this indication declined as the year progressed. CONCLUSIONS: The ACTH
      stimulation test was often used inappropriately for patients with septic shock.
      Over time, there appeared to be a trend away from use of this test in this
      patient population, perhaps reflecting increasing awareness of the lack of
      benefit.

PMID- 22478948
TI  - Influence of age on frequency of vancomycin dosing.
AB  - BACKGROUND: Vancomycin is commonly prescribed at the authors' institution because
      of a high prevalence of invasive infections caused by methicillin-resistant
      Staphylococcus aureus (MRSA) in a generally younger population. The most commonly
      prescribed empiric dosing interval is every 12 h (q12h). However, observations
      have suggested that younger adult patients require more frequent dosing, such as
      every 8 h (q8h). Initial underdosing of vancomycin may increase the risk of
      antibiotic failure. OBJECTIVE: To determine whether patients under 40 years of
      age are more likely than older patients to require q8h dosing of vancomycin and
      whether recommendations can be made to alter current prescribing practices.
      METHODS: This retrospective unmatched case-control study involved patients who
      had received vancomycin for suspected or confirmed severe MRSA infections. The
      cases were patients who had been confirmed as requiring q8h dosing, and the
      controls were patients who had been confirmed as requiring q12h dosing (on the
      basis of target predose serum levels). The influence of age (the predictor
      variable) on outcome (the vancomycin regimen) was evaluated by logistic
      regression. RESULTS: The odds ratio for patients under 40 years of age requiring
      q8h dosing was 3.1 (95% confidence interval 1.5-6.3) (p = 0.002). Sixty percent
      of patients under 40 ultimately required a q8h regimen to achieve target predose
      serum levels. Patients who required q8h dosing took longer to achieve their first
      therapeutic serum level than those with q12h dosing (median 6 versus 4 days; p <
      0.001). CONCLUSIONS: In this patient population, age less than 40 years was a
      strong predictor for requiring more frequent dosing of vancomycin. The authors
      suggest that doses of 15 mg/kg IV q8h be used empirically for younger patients
      with severe infections and normal renal function.

PMID- 22478949
TI  - Medication error reporting systems: a survey of canadian intensive care units.
AB  - BACKGROUND: Patients in the intensive care unit (ICU) have complex problems and
      experience many medical errors. Currently, little is known about the measurement
      of medication errors and adverse drug events in Canadian ICUs. OBJECTIVE: To
      investigate methods of measuring medication errors and adverse drug events in
      ICUs in Canada. METHODS: A questionnaire was constructed and uploaded to an
      online survey tool, SurveyMonkey. Through the mailing list software of the
      Critical Care Pharmacy Specialty Network of the Canadian Society of Hospital
      Pharmacists, the survey was sent by e-mail to 146 pharmacists working in 79 ICUs
      across Canada; 2 reminder e-mails followed. The survey was open from July 18 to
      September 18, 2007. RESULTS: A total of 34 individual responses were received
      from 31 (39%) of the 79 ICUs. Responses were from academic hospitals (11/31
      [35%]), community teaching hospitals (9/31 [29%]), and community nonteaching
      hospitals (11/31 [35%]). Twenty-six (84%) of the 31 responding ICUs had a process
      for tracking medication errors and adverse drug events: non-anonymous voluntary
      reporting (19 or 73%), direct observation (14 or 54%), anonymous voluntary
      reporting (12 or 46%), chart review (6 or 23%), computerized system (3 or 12%),
      trigger tools (2 or 8%), pharmacist intervention (2 or 8%), and weekly ICU
      "safety huddles" (1 or 4%). Fourteen (54%) of the 26 ICUs that had a method of
      measuring medication errors and adverse drug events had implemented changes to
      address identified problems. CONCLUSIONS: Most respondents were measuring the
      frequency of medication errors and adverse drug events, but a wide variety of
      methods were in use. Only about half of the ICUs had implemented changes as a
      result of these measurements. There is an opportunity to improve standardization
      of the measurement of medication errors and adverse drug events in Canadian ICUs.

PMID- 22478950
TI  - Stability of diclofenac sodium oral suspensions packaged in amber polyvinyl
      chloride bottles.
AB  - BACKGROUND: Prescribing of diclofenac for children usually involves a dose
      different from commercially available strengths. This drug is available only as
      tablets, which can be divided only so many times before the dose obtained becomes
      inaccurate. In addition, children may have difficulty swallowing tablets. For
      these reasons, a compounding formula for a liquid dosage form is essential to
      ensure effective delivery of the drug to pediatric patients. OBJECTIVES: To
      develop a compounding formula for diclofenac sodium and to determine the extended
      physical and chemical stability of this compound when stored in amber polyvinyl
      chloride (PVC) prescription bottles under refrigeration and at room temperature.
      METHODS: A suspension of diclofenac sodium (10 mg/mL) was prepared from
      commercially available diclofenac sodium tablets, with Ora-Blend as the
      suspending and flavouring agent. The suspension was packaged in 60-mL amber PVC
      prescription bottles and stored at either room temperature (23 degrees C) or
      under refrigeration (5 degrees C). Samples were collected on days 0, 7, 14, 21,
      27, 56, and 93. Chemical stability was determined using a validated stability
      indicating high-performance liquid chromatography method. At each sampling time,
      the suspensions were checked for changes in appearance (i.e., colour, layering,
      caking, ease of resuspension), odour, and pH. RESULTS: The diclofenac sodium
      suspensions were very stable, retaining at least 99.5% of the original
      concentration for up to 93 days, regardless of storage temperature. There were no
      apparent changes in the physical appearance of the suspensions, nor were there
      any substantial changes in odour or pH. CONCLUSIONS: Suspensions of diclofenac
      sodium (10 mg/mL) were quantitatively stable but difficult to prepare because of
      the enteric coating of the tablets. Therefore, it is recommended that diclofenac
      powder be used for the preparation of suspensions. For pediatric use,
      palatability is a consideration, and a masking agent should be added before
      administration. An expiry date of up to 93 days is suggested.

PMID- 22478951
TI  - Association Between Use of Proton Pump Inhibitors and a Clostridium difficile
      Associated Disease Outbreak: Case-Control Study.
AB  - BACKGROUND: The use of proton pump inhibitors (PPIs) has been implicated as a
      potential contributor to the development of Clostridium difficile-associated
      disease (CDAD) because of the ability of these drugs to substantially reduce the
      bactericidal effect of gastric acid. This study focused on the impact of PPIs,
      among other known risk factors, during an outbreak of CDAD in a hospital setting.
      OBJECTIVES: The primary objective was to determine whether there was an
      association between current use of a PPI and the CDAD outbreak. Secondary
      objectives were to evaluate any correlations between the CDAD outbreak and past
      use of PPIs, use of antibiotics, diabetes mellitus, enteral feeding, cancer,
      gastrointestinal surgery, inflammatory bowel disease, and previous care or
      residence in an institutional setting. METHODS: A retrospective case-control
      study was conducted. One hundred and fifty cases of hospital-acquired Clostridium
      difficile were identified. Patients were individually matched to controls for
      age, sex, date of admission to hospital, and hospital unit. The groups were
      compared with respect to each exposure. RESULTS: Eight case patients could not be
      matched with suitable controls. Therefore, data from 142 cases and 142 controls
      were analyzed. There was no association between current use of a PPI and the CDAD
      outbreak (odds ratio [OR] 1.0, 95% confidence interval [CI] 0.99-1.01).
      Similarly, there was no correlation between the CDAD outbreak and diabetes,
      enteral feeding, cancer, gastrointestinal surgery, inflammatory bowel disease, or
      previous care or residence in an institution. However, the development of CDAD
      was positively associated with use of antibiotics within the 30 days preceding
      the infection (OR 12.0, 95% CI 4.0-35.7) and with past use of a PPI (OR 2.4, 95%
      CI 1.4-4.3). CONCLUSIONS: The development of CDAD during a hospital outbreak was
      associated with use of antibiotics and with past, not current, use of PPIs.

PMID- 22478952
TI  - Patient's Perspectives on Team-Based Care by a Clinical Pharmacist: Case Report.

PMID- 22478953
TI  - Using clinical pharmacy support technicians to optimize pharmaceutical care in
      the intensive care unit.

PMID- 22478954
TI  - Practice spotlight: denise sprague.

PMID- 22478955
TI  - Clopidogrel and proton pump inhibitors: a new drug interaction?

PMID- 22478956
TI  - Are tight glycemic targets achieved through intensive insulin infusion still
      applicable in the intensive care unit?

PMID- 22478958
TI  - Tribute to the reviewers of the canadian journal of hospital pharmacy.

PMID- 22478957
TI  - Prescribing by Pharmacist's and Collaborative Care: Are We Ready to Accept the
      Baton and Get in the Race?

PMID- 22478959
TI  - CSHP Professional Practice Conference 2010: Poster Abstracts/Conference sur la
      pratique professionnelle 2010 de la SCHP: Resumes des affiches.

PMID- 22478960
TI  - 2010 CSHP National Awards Program Winners Programme national des prix 2010 de la
      SCPH : laureats et laureates.

PMID- 22478961
TI  - Another devil of a year.

PMID- 22478962
TI  - Value for money and hospital pharmacists.

PMID- 22478963
TI  - Evidence to support development of pharmacy services: how much or how little do
      we need?

PMID- 22478964
TI  - A tribute to charlie bayliff.

PMID- 22478965
TI  - Care providers' satisfaction with restructured clinical pharmacy services in a
      tertiary care teaching hospital.
AB  - BACKGROUND: At the time this study was undertaken, clinical pharmacy services at
      the authors' institution, a tertiary care teaching hospital, were largely
      reactive in nature, with patients and units receiving inconsistent coverage.
      OBJECTIVE: To develop an evidence-based model of proactive practice and to
      evaluate the satisfaction of pharmacists and other stakeholders after
      restructuring of clinical pharmacy services. METHODS: The literature was reviewed
      to determine a core set of pharmacist services associated with the greatest
      beneficial impact on patients' health. On the basis of established staffing
      levels, the work schedule was modified, and pharmacists were assigned to a
      limited number of patient care teams to proactively and consistently provide
      these core services. Other patient care teams continued to receive reactive
      troubleshooting-based services, as directed by staff in the pharmacy dispensary.
      A satisfaction survey was distributed to all pharmacists, nurses, and physicians
      18 months after the restructuring. RESULTS: Of the 26 pharmacists who responded
      to the survey, all agreed or strongly agreed that the restructuring of services
      had improved job satisfaction and patient safety and that other health care
      professionals valued their contribution to patient care. Nurses and physicians
      from units where pharmacists had been assigned to provide proactive services
      perceived pharmacist services more favourably than those from units where
      pharmacist services were reactive. Pharmacists, nurses, and physicians all felt
      that proactive pharmacist services should be more widely available. Challenges
      reported by pharmacists included increased expectations for documentation and
      guilt about "cutting back" services where they had previously been provided.
      CONCLUSIONS: Restructuring clinical pharmacy services in an evidence-based manner
      improved pharmacists' satisfaction and created demand from other stakeholders to
      provide this level of service for all patients.

PMID- 22478966
TI  - Stability of norepinephrine solutions in normal saline and 5% dextrose in water.
AB  - BACKGROUND: Most previous stability studies for norepinephrine have reported the
      percentage of drug remaining in IV solutions after only 24 h. No previously
      published study has evaluated the effect of light on the stability of this drug.
      OBJECTIVE: To evaluate the stability of norepinephrine (64 mg/L) in either normal
      saline (NS; 0.9% sodium chloride) or 5% dextrose in water (D5W) with storage at
      either 4 degrees C or room temperature (23 degrees C) in polyvinyl chloride (PVC)
      bags exposed to or protected from normal room lighting for 2 months. METHODS:
      Thirty-two PVC bags were prepared, each containing norepinephrine at 64 mg/L;
      half of the bags had normal saline as the diluent and the other half had D5W. The
      bags were stored at either 4 degrees C or room temperature (23 degrees C), with
      protection from or exposure to ambient fluorescent room light. Overall, there
      were 4 bags for each combination of diluent, temperature, and light condition.
      The concentration of norepinephrine in each bag was determined by a validated,
      stability-indicating liquid chromatographic method on study days 0, 1, 2, 3, 4,
      8, 9, 10, 11, 14, 18, 21, 23, 25, 28, 30, 36, 42, and 61. RESULTS: Analysis of
      variance revealed differences in percentage remaining as a function of study day
      (p < 0.001) and light conditions (p < 0.001), but not diluent (p = 0.06) or
      storage temperature (p > 0.99). CONCLUSIONS: Solutions of norepinephrine 64 mg/L
      in NS or D5W can be stored in PVC bags at 4 degrees C for up to 61 days with
      protection from light. This expiry date allows for up to 24 h storage at 23
      degrees C. Solutions that are not protected from light will retain only 90% of
      the initial concentration after storage for 39 days at 4 degrees C. This storage
      period could include up to 24 h at room temperature, without protection from
      light.

PMID- 22478967
TI  - [Not Available].
AB  - BACKGROUND: Although the concept of clinical pharmacy was originally developed
      some time ago, in the 1960s, there is a wide variety of programs in existence, as
      well as great disparity between programs where the presence of a pharmacist is
      provided in outpatient and inpatient settings. OBJECTIVE: To test a method for
      upgrading pharmaceutical care areas in a hospital setting. METHOD: This
      descriptive study was conducted at the Sainte-Justine university health centre, a
      500-bed mother-and-child hospital. The pharmaceutical care area that was used to
      exemplify the upgrading method was pediatric hematology-oncology. A 3-step method
      was used: review of the scientific literature, creation of a profile of the
      targeted area, and upgrading of the practice level according to the pre- and post
      upgrading profile of the pharmaceutical activities in the area. RESULTS: A total
      of 108 articles were identified in a search of the PubMed database, of which 22
      were retained. After a complementary manual search, a total of 36 articles were
      evaluated. The articles retained included 3 guidelines, 11 development studies, 1
      review of scientific literature, 6 pre- and post-intervention studies, and 15
      quasi-experimental studies. Although patients in the pediatric hematology
      oncology area account for only 5% of admissions to this hospital, the cases are
      highly complex, in terms of both the codification of the care phase and the
      potential for pharmaceutical intervention per admission. CONCLUSION: There are
      few data to illustrate a method for upgrading practice in a pharmaceutical care
      area. This study tested a method for upgrading pharmaceutical care in a pediatric
      hematology-oncology service, with a review of the scientific literature, a
      profile of the area, and the pharmacists' pre- and post-upgrading job description
      in this area. [Publisher's translation].

PMID- 22478968
TI  - Quality and usability of common drug information databases.
AB  - BACKGROUND: Pharmacists' access to user-friendly electronic drug information
      databases that can quickly provide accurate, up-to-date information has become
      increasingly important. Unfortunately, decisions about purchasing subscriptions
      to such services are not always made objectively. Previously published studies
      have compared drug information databases, but there are no recent analyses from
      the perspective of Canadian hospital pharmacists. OBJECTIVE: To determine overall
      preferences among the most commonly used online drug information databases, based
      on an appraisal of the quality, performance, and usability of the databases and
      users' preferences. METHODS: Qualitative and quantitative analyses with
      descriptive and inferential statistics were used to compare the Clinical
      Pharmacology, Lexi-Comp Online, and Micromedex databases. Quality scores were
      determined from investigators' consensus ratings across 5 categories of quality
      indicators. Performance scores were determined according to the ability of a
      database to answer 15 clinical drug information questions. Usability scores were
      determined from user ratings in 7 domains. Users' preferences were assessed
      through rankings of the databases by 26 practising pharmacists. RESULTS: The
      highest quality and performance scores were awarded to Lexi-Comp Online, whereas
      Micromedex received the lowest overall usability score, attributable to poor
      scores for layout, navigation, and speed. Lack of Canadian content was identified
      as a major disadvantage of the Clinical Pharmacology database. Users ranked
      Micromedex significantly lower than the other databases, whereas the majority of
      users ranked Lexi-Comp Online as the most preferred database. CONCLUSIONS: Lexi
      Comp Online appeared to be the most preferred database, whereas Micromedex was
      clearly the least preferred database. These findings should be considered in
      future decisions about purchasing database subscriptions.

PMID- 22478969
TI  - Specialized pharmacy oncology technician: experience at the ridge meadows
      hospital.

PMID- 22478970
TI  - Retrospective analysis of adherence to thromboprophylaxis after orthopedic
      surgery in a community hospital.

PMID- 22478971
TI  - Practice spotlight: supportive care research in pediatric oncology.

PMID- 22478972
TI  - Should All Pharmacists Entering a Patient Care Setting Have Completed (at Least)
      a Canadian Hospital Pharmacy Residency Board-Accredited Residency?

PMID- 22478973
TI  - Physical compatibility of high-concentration bupivacaine with hydromorphone,
      morphine, and fentanyl.

PMID- 22478975
TI  - Distinguished service award 2009/2010 presented by ortho biotech - division of
      janssen ortho inc emily lap sum musing.

PMID- 22478974
TI  - Are the Results of the RE-LY Trial Reliable?

PMID- 22478976
TI  - What the Saskatchewan Roughriders Have Taught Me about Pharmacy.

PMID- 22478978
TI  - Gatineau park, quebec.

PMID- 22478977
TI  - Uniform Format for Disclosure of Conflict of Interest in the CJHP.

PMID- 22478979
TI  - Initial vancomycin dosing recommendations for critically ill patients undergoing
      continuous venovenous hemodialysis.
AB  - BACKGROUND: Delaying appropriate antimicrobial therapy for critically ill
      patients increases the risk of death. Currently, there are insufficient data to
      guide initial vancomycin dosing for patients undergoing continuous venovenous
      hemodialysis (CVVHD). OBJECTIVE: To develop practical recommendations for initial
      dosing of vancomycin, based on the pharmacokinetics of this drug in critically
      ill patients undergoing CVVHD. METHODS: A chart review was conducted for 24
      critically ill adult patients who had undergone concurrent CVVHD and vancomycin
      therapy. Mean pharmacokinetic parameters were determined, along with practical
      recommendations for initial vancomycin dosing that targeted steady-state trough
      concentrations for patients receiving intermittent infusions and steady-state
      levels for those receiving continuous infusions between 15 and 20 mg/L. Monte
      Carlo simulation was used to develop the initial vancomycin dosing
      recommendations. RESULTS: The mean (95% confidence interval) pharmacokinetic
      parameters for vancomycin (elimination rate constant 0.0315 [0.0254-0.0391], half
      life 22.0 h [17.72-27.24 h], volume of distribution 0.96 L/kg [0.77-1.20 L/kg],
      and clearance 2.4 L/h [1.97-2.92 L/h]) indicated that initial intermittent IV
      dosing of 1.25-1.5 g q24h or 15 mg/kg q24h would be suitable. For continuous
      infusion, a 1.5-g IV loading dose followed by continuous infusion of 1-1.5 g IV
      over 24 h (42-62 mg/h) would be recommended. However, Monte Carlo simulation
      revealed that the probability of achieving desired concentrations between 15 and
      20 mg/L with any of these initial regimens is low. CONCLUSIONS: There was
      considerable variation in vancomycin pharmacokinetics in this patient population.
      The observations reported here raise concerns about the reliability of numerous
      empiric dosing recommendations derived from small pharmacokinetic studies in
      heterogeneous populations. Follow-up therapeutic drug monitoring is essential to
      ensure that concentrations remain within the target range.

PMID- 22478980
TI  - Use of evidence-based therapy at discharge for patients with acute myocardial
      infarction: retrospective audit of medical records.
AB  - BACKGROUND: Various guidelines are available outlining optimal therapy for
      patients with acute myocardial infarction. Canadian institutions providing care
      for such patients have been encouraged to evaluate their care processes using
      specific indicators. OBJECTIVE: To determine the proportion of patients with
      acute myocardial infarction discharged from a single health authority for whom
      acetylsalicylic acid (ASA), adrenergic beta-receptor antagonists (beta-blockers),
      angiotensin-converting enzyme (ACE) inhibitors, or 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors (statins) had been prescribed. METHODS:
      Patients treated over a 12-month period (April 1, 2004, to March 31, 2005) for
      whom the most responsible diagnosis was acute myocardial infarction were eligible
      for inclusion in this review. Retrieved data included diagnosis, demographic
      information, comorbidities, and medications at the time of admission and
      discharge. Rates of discharge prescribing for the 4 drug classes were calculated
      for all patients and for "ideal" patients (those without documented
      contraindications). Rates were compared with published benchmark values. RESULTS:
      Medical records for a total of 346 eligible patients were reviewed. Mean age was
      65.3 years (standard deviation 13.4 years), and 226 (65.3%) of the patients were
      male. The coded diagnosis was ST-elevation myocardial infarction for 91 patients
      (26.3%), non-ST-elevation myocardial infarction for 164 (47.4%), and myocardial
      infarction not specified for 91 (26.3%). For "ideal" patients, the prescribing
      rates were 99.0% (308 of 311 patients) for ASA, 96.3% (310 of 322 patients) for
      beta-blockers, 90.4% (264 of 292 patients) for ACE inhibitors, and 88.8% (278 of
      313 patients) for statins. CONCLUSIONS: Rates of prescribing of ASA, beta
      blockers, ACE inhibitors, and statins for "ideal" patients discharged after
      treatment for acute myocardial infarction exceeded the published Canadian
      benchmark rates (>= 90% for ASA, >= 85% for beta-blockers and ACE inhibitors, >=
      70% for statins).

PMID- 22478981
TI  - Stability of commonly used antibiotic solutions in an elastomeric infusion
      device.
AB  - BACKGROUND: The Accufuser silicone-based elastomeric infusion device has recently
      been approved for the Canadian market. OBJECTIVE: To evaluate the stability of 5
      antibiotics (cefazolin, ceftazidime, ceftriaxone, clindamycin, and vancomycin) in
      either 5% dextrose in water (D5W) or 0.9% sodium chloride in water (NS) after
      storage in Accufuser disposable silicone balloon infusers. METHODS: The study
      drugs were reconstituted, according to the manufacturers' directions, in
      polyvinyl chloride minibags with either D5W or NS, at 2 different concentrations.
      The resulting solutions were transferred to disposable silicone balloon infusers
      for storage at 4 degrees C or at room temperature (23 degrees C). The
      concentration of each drug in each solution was determined by validated stability
      indicating liquid chromatographic methods after storage for 14 to 31 days.
      RESULTS: Solutions of ceftriaxone in either diluent retained more than 95.2% of
      the initial concentration for 2 days at room temperature and more than 91.6% of
      the initial concentration for 14 days at 4 degrees C. Solutions of cefazolin in
      D5W or NS retained more than 90% of the initial concentration for at least 3 days
      at room temperature and for at least 26 days at 4 degrees C. Solutions of
      ceftazidime in D5W or NS retained more than 90% of the initial concentration for
      only 1 day when stored at room temperature and for at least 4 days at 4 degrees
      C. Solutions of clindamycin or vancomycin in D5W or NS retained 90% of the
      initial concentration for at least 7.5 days at room temperature and at least 90%
      of the initial concentration for at least 27.8 days at 4 degrees C. CONCLUSIONS:
      Previously reported expiration dates for solutions stored in elastomeric infusion
      devices were not based on 95% confidence intervals and were often longer than
      expiration dates determined from the studies reported here, which are based on
      95% confidence intervals. Comparison of the observed concentrations remaining
      between previously published studies and the studies reported here indicates that
      the Accufuser elastomeric infusion device did not adversely affect the stability
      of these drugs.

PMID- 22478982
TI  - Acceptability and face validity of a geriatric self-medication assessment tool.
AB  - BACKGROUND: A majority of community-dwelling older adults manage their own
      medication regimens. This study describes the development and first phase of
      testing of the Self-Medication Assessment Tool (SMAT), designed to screen for
      cognitive and functional deficits in relation to medication self-management among
      community-dwelling geriatric patients. OBJECTIVE: To evaluate the face validity
      of the SMAT and to determine its acceptability among pharmacists. METHODS: An
      instrument was designed, with 5 assessment scales to measure function, cognition,
      medication recall, and 2 aspects of adherence. The instrument included a
      standardized test kit and instructions for testers. Focus groups interviews,
      individual interviews, and surveys were used to determine the reactions of
      community and hospital-based pharmacists to the tool. Transcripts of the focus
      group and individual interviews were coded for main themes. Pharmacists' ratings
      of usefulness, thoroughness, and ease of use, as well as their willingness to use
      the instrument, were compared with a neutral rating on a 7-point scale by means
      of 1-sample t tests. RESULTS: Focus group interviews or individual interviews
      were conducted with 17 pharmacists and 3 pharmacy students (out of a potential
      population of about 300) who responded to an invitation to participate. The
      pharmacists felt that the tool would be useful in identifying difficulties with
      medication management and potential interventions, and they expressed a
      willingness to use it in their respective practices. Pharmacists working in
      hospital settings were slightly more willing than community pharmacists to use
      the tool. Interviewees highlighted ways to improve the tool before testing of its
      psychometric properties in the planned second phase of this project. CONCLUSIONS:
      The SMAT had strong face validity and was particularly acceptable for use by
      pharmacists in hospital settings.

PMID- 22478983
TI  - Probable topiramate-induced hemiparesis.

PMID- 22478985
TI  - Practice spotlight: health outcomes analyst in oncology.

PMID- 22478984
TI  - [Not Available].

PMID- 22478986
TI  - Should IV Antibiotics Be Administered by Prolonged Infusion?

PMID- 22478987
TI  - Experience with extended infusion of piperacillin-tazobactam at a teaching
      hospital.

PMID- 22478989
TI  - The end is nigh, and the work has just begun.

PMID- 22478990
TI  - Facts and comparisons: journal updates and performance indicators.

PMID- 22478988
TI  - Prescribing by pharmacists: information paper (2009).

PMID- 22478991
TI  - Audit of physicians' adherence to a preprinted order set for community-acquired
      pneumonia.
AB  - BACKGROUND: Community-acquired pneumonia is the seventh leading cause of death in
      Canada. Previous studies have shown reductions in both mortality rate and length
      of hospital stay with the use of guideline-concordant empiric therapy and
      standardized preprinted orders. OBJECTIVES: The primary objective was to
      determine adherence to the preprinted order for community-acquired pneumonia at
      the University Hospital of Northern British Columbia (UHNBC). The study also had
      the following secondary objectives: to assess the appropriateness of prescribing
      of levofloxacin in relation to institutional recommendations; to determine
      adherence with recent guidelines from the Infectious Diseases Society of America
      (IDSA) and the American Thoracic Society (ATS) for the treatment of community
      acquired pneumonia; and to determine all-cause mortality, duration of IV
      antibiotic therapy, and length of stay for the various regimens reviewed.
      METHODS: A retrospective observational chart review was conducted of patients
      with community-acquired pneumonia who were admitted between November 2007 and
      February 2008. Exclusion criteria were designed to eliminate patients who did not
      have this condition. Descriptive statistics were used to assess adherence with
      the preprinted order. Secondary outcomes were analyzed with the Pearson chi(2)
      test, t tests, and analysis of variance. RESULTS: In total, the charts for 113
      patients were reviewed, and 58 patients were included in the study. The
      preprinted order for community-acquired pneumonia was used for 25 (43%) of the 58
      patients; however, for only 4 (7%) of these admissions were all sections of the
      preprinted order used correctly. No statistically significant differences in
      length of stay were found for any of the antibiotic combinations assessed.
      However, the proportion of patients treated according to the IDSA-ATS guidelines
      was significantly greater when the preprinted order was used (p = 0.012). In
      addition, use of the preprinted order encouraged assessment of the patient's
      pneumococcal vaccination status (9 [25%] of 25 patients versus 3 [9%] of 33
      patients) and utilization of the pneumonia severity index (13 [52%] of 25
      patients versus 0 [0%] of 33 patients). CONCLUSION: The preprinted order for
      community-acquired pneumonia at UHNBC was not being utilized to its fullest.
      However, when it was used, it increased guideline-concordant empiric therapy and
      encouraged assessment of patients' pneumococcal vaccination status and pneumonia
      severity index.

PMID- 22478992
TI  - Development of a supervisory skills course for hospital pharmacy workplaces.
AB  - BACKGROUND AND OBJECTIVE: Many Canadian hospital pharmacies are experiencing
      difficulties recruiting supervisory personnel. It was expected that, through a
      "learning-by-doing" course, pharmacy staff would learn to apply basic skills in
      the day-to-day supervision of pharmacy operations and human resources and to
      apply the principles of supervisory documentation. METHODS: A supervisory skills
      course targeted to pharmacy staff members was developed and implemented by the
      pharmacy department of a large urban health region. The course was initially
      offered to practising pharmacy technicians. The course design emphasized a
      constructivist framework incorporating authentic learning and reflective practice
      during seminars, with experiential and self-directed learning in the workplace.
      Preceptors assisted learners to achieve the course goals. Learners and preceptors
      provided feedback about hours spent (as the course progressed) and about their
      satisfaction with the course itself (at the end of the course). Learners and
      preceptors completed a post-program evaluation 2 months after completing the
      course to help in the assessment of the transfer of learning (lasting impact)
      associated with the course. Overall performance in the course was assessed on a
      pass/fail basis. RESULTS: Eighteen pharmacy technicians were admitted to the
      program, but one withdrew because of a job change. All learners successfully
      completed the course. Two months after the course, learners and preceptors
      described enhanced organization, time management, leadership, communication, and
      conflict-resolution skills on the part of learners, as well as their increased
      confidence, maturity, and ability to supervise staff. Learners' evaluations
      revealed a broadened perspective of pharmacy. The preceptors valued the
      enhancement of learners' skills and their increased enthusiasm. At the time of
      writing, 6 of the participants had secured supervisory positions. CONCLUSION:
      Creating formal instruction that engages pharmacy staff to pursue management
      positions is challenging. Instructional design grounded in constructivist theory
      and incorporating authentic learning experiences and reflection resulted in high
      learner satisfaction with learning outcomes.

PMID- 22478993
TI  - Stability of trisodium citrate and gentamicin solution for catheter locks after
      storage in plastic syringes at room temperature.
AB  - BACKGROUND: Catheter-related infections are a major problem for hemodialysis
      patients with central venous catheters for vascular access. Catheter lock
      solutions containing an anticoagulant are used to maintain the patency of the
      catheter between hemodialysis sessions. There is evidence that the use of lock
      solutions containing an antibiotic is associated with lower rates of infection
      but also that these solutions can kill microbes in colonized catheters and thus
      avoid the risks and costs associated with replacing the catheter. OBJECTIVE: This
      stability study was conducted to determine whether an extemporaneously prepared
      gentamicin-citrate catheter lock solution would retain its potency over time,
      thus allowing for advance preparation of the solution. METHODS: Catheter lock
      solutions containing gentamicin alone, citrate alone, and the combination of
      gentamicin and citrate were prepared aseptically and packaged in polyethylene
      syringes. The syringes were stored at room temperature. At timed intervals over
      112 days, samples were withdrawn for analysis by means of validated high
      performance liquid chromatography. RESULTS: None of the 3 lock solutions showed
      any evidence of degradation during the 112-day observation period. In the
      formulation containing both gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL
      (4%), there was no change in the concentration of either gentamicin (p = 0.34) or
      citrate (p = 0.55). Linear regression analysis of the concentration-time data for
      the combined formulation showed that 99.97% of the labelled amount of gentamicin
      and 101.30% of the labelled amount of citrate remained at day 112. The lower
      limit of the 95% confidence intervals indicated that more than 98.17% of the
      gentamicin and more than 99.57% of the citrate remained on day 112. CONCLUSION:
      The results of this study will allow pharmacies to extemporaneously compound the
      combined gentamicin-citrate catheter lock solution in advance of use. The method
      described here will yield a stable product for use in clinical applications.

PMID- 22478994
TI  - Endocarditis Due to Listeria monocytogenes in an Academic Teaching Hospital: Case
      Report.

PMID- 22478995
TI  - Ertapenem-induced reduction in valproate levels: case report and review of the
      literature.

PMID- 22478996
TI  - Asynchronous validation and documentation of sterile compounding in a hospital
      pharmacy.

PMID- 22478997
TI  - Practice spotlight: pharmacists in an antimicrobial stewardship program.

PMID- 22478998
TI  - Should hospital pharmacy drug budgets be the responsibility of each individual
      department in an institution, or should such budgets be controlled centrally by
      the pharmacy department?

PMID- 22478999
TI  - Are You GS1-Compliant? One Hospital Pharmacy's Experience.

PMID- 22479000
TI  - Explaining the RE-LY Trial.

PMID- 22479001
TI  - And so the journey continues.

PMID- 22479002
TI  - "Partners in crime": pharmacists and pharmacy technicians.

PMID- 22479003
TI  - Best possible medication history in the emergency department: comparing pharmacy
      technicians and pharmacists.
AB  - BACKGROUND: Obtaining an accurate and complete medication list (i.e., the best
      possible medication history [BPMH]) is the first step in completing medication
      reconciliation. The ability of pharmacy technicians to obtain medication
      histories, relative to that of pharmacists, has not been formally assessed.
      OBJECTIVES: To determine whether pharmacy technicians at the authors' institution
      could obtain a BPMH as accurately and completely as pharmacists and if both
      groups met national norms for unintentional discrepancies and the success index
      for medication reconciliation. METHODS: Pharmacy technicians were trained in
      obtaining a BPMH at the beginning of the study, before any patients were
      enrolled. Patients presenting to the emergency department were prospectively
      enrolled to be interviewed separately by both a pharmacist and a technician, with
      information recorded on standard medication reconciliation forms. The completed
      forms for each patient were compared following each set of interviews, and
      discrepancies were clarified with the patient. RESULTS: Fifty-nine patients were
      included in the study, and 3 pharmacists and 2 technicians obtained the
      histories. There was no significant difference between pharmacists and
      technicians in terms of discrepancies involving prescription drugs (chi(2) =
      0.52, df = 1, n = 118, p = 0.47, Cramer's V for effect size = 0.07) or over-the
      counter medications (chi(2) = 0.09, df = 1, n = 118, p = 0.77, Cramer's V =
      0.03). The mean number of discrepancies per patient did not differ significantly
      between the pharmacists and technicians (t = 0.15, df = 58, p = 0.88 for
      prescription drugs; t = -0.22, df = 58, p = 0.83 for over-the-counter products).
      For both groups, the number of unintentional discrepancies per patient was
      significantly lower and the success index for medication reconciliation
      significantly higher than the national average. CONCLUSIONS: Trained pharmacy
      technicians at the authors' institution were able to obtain a BPMH with as much
      accuracy and completeness as pharmacists. Both groups were significantly superior
      to the national average in terms of unintentional discrepancies and success index
      for medication reconciliation.

PMID- 22479004
TI  - Stability of Vancomycin 25 mg/mL in Ora-Sweet and Water in Unit-Dose Cups and
      Plastic Bottles at 4 degrees C and 25 degrees C.
AB  - BACKGROUND: Solutions of vancomycin for oral administration are not available
      commercially in Canada or the United States but are needed for patients who
      cannot swallow capsules. OBJECTIVE: To evaluate the stability of vancomycin
      solutions stored in unit-dose cups and plastic bottles under refrigeration (4
      degrees C) and at room temperature (25 degrees C) for up to 75 days. METHODS:
      Vancomycin 25 mg/mL in Ora-Sweet vehicle and water (1:1 ratio by volume) was
      dispensed into opaque blue polyethylene unit-dose cups with aluminum seal (14
      replicates) or amber plastic prescription bottles (6 replicates). Seven cups and
      3 bottles were refrigerated (4 degrees C), and the remainder of the containers
      were stored at room temperature (25 degrees C). At the time of preparation and at
      15, 30, 40, 50, 63, and 75 days, 3 aliquots were collected from one of the cups
      and from every bottle and were stored frozen (-85 degrees C) until the time of
      analysis. Physical characteristics were evaluated at each time point, including
      measurement of pH and visual assessment of colour and precipitation. After
      thawing, the samples were analyzed in triplicate by a validated stability
      indicating high-performance liquid chromatography method. A solution was
      considered stable if 90% of the initial concentration of vancomycin was
      maintained. RESULTS: No notable changes in colour, taste, or pH were observed in
      vancomycin solutions stored in the unit-dose cups at 4 degrees C or 25 degrees C
      or in the plastic bottles stored at 4 degrees C over the 75-day study period.
      Starting on day 63, a white precipitate was observed in the solutions stored in
      plastic bottles at 25 degrees C, but there were no notable changes in taste or pH
      during the 75-day period. The 95% confidence interval of the slope of the curve
      relating concentration to time, determined by linear regression, indicated that
      vancomycin solutions stored in cups or bottles at 4 degrees C would maintain at
      least 93.6% of the initial vancomycin concentration for 75 days and that
      solutions stored at 25 degrees C would maintain at least 90.0% of the initial
      concentration for 30 days (cups) or 26 days (bottles), with 95% confidence.
      CONCLUSIONS: Vancomycin 25 mg/mL stored in unit-dose cups or plastic bottles at 4
      degrees C was stable for at least 75 days, whereas solutions stored in cups or
      bottles at 25 degrees C are expected to be stable for 30 or 26 days,
      respectively.

PMID- 22479005
TI  - Comparison of Continuous and Intermittent IV Infusion of Vancomycin: Systematic
      Review.
AB  - BACKGROUND: There is some evidence that administration of vancomycin by
      continuous infusion has pharmacokinetic and pharmacodynamic advantages over
      traditional intermittent dosing. Whether these advantages translate into clinical
      efficacy remains controversial. OBJECTIVE: To review the literature comparing
      continuous infusion of vancomycin and conventional intermittent IV dosing in
      terms of efficacy and safety. METHODS: A literature search was conducted in the
      PubMed/MEDLINE and Embase databases and the Cochrane Central Register of
      Controlled Trials, and by means of the Google search engine, and the reference
      lists of pertinent articles were searched manually. All human studies published
      in English or French that evaluated vancomycin given by continuous and
      intermittent IV infusion were reviewed. Articles that did not include a
      comparator arm and those that assessed continuous and intermittent
      intraperitoneal infusions were excluded. The level of evidence of each study was
      categorized according to the US Preventive Services Task Force rating scale.
      RESULTS: In total, 9 studies were identified: 1 in a pediatric population and 8
      in adult populations. Of the 3 studies with the highest quality of evidence
      (level I), one demonstrated pharmacodynamic advantages with continuous infusion
      of vancomycin. Of the 6 studies representing a moderate level of evidence (level
      II), 3 also favoured continuous infusion in terms of pharmacokinetic and
      pharmacodynamic outcomes, but the findings in terms of clinical outcomes were
      mixed. CONCLUSIONS: Current evidence evaluating the pharmacokinetic and
      pharmacodynamic advantages and clinical efficacy of continuous versus
      intermittent vancomycin infusions is inconsistent and does not support the
      routine use of continuous infusion for the treatment of multidrug-resistant gram
      positive infections.

PMID- 22479006
TI  - Interaction between Methadone and Ciprofloxacin.

PMID- 22479007
TI  - Development of a multisite distribution rotation for pharmacy practice residents.

PMID- 22479008
TI  - Practice spotlight: staff development and practice evaluation pharmacist.

PMID- 22479010
TI  - A vision for hospital pharmacy in Canada.

PMID- 22479009
TI  - Should Pharmacy Technicians Provide Clinical Services or Perform Patient Care
      Activities in Areas without a Pharmacist?

PMID- 22479011
TI  - Transition from hospital to home: can pharmacists' interventions improve
      patients' outcomes?

PMID- 22479012
TI  - La transition de l'hopital a la maison : les interventions des pharmaciens
      peuvent-elles ameliorer les resultats pour les patients?

PMID- 22479013
TI  - Pharmacists making house calls: innovative role or overkill?
AB  - BACKGROUND: The Medication Management Program was established at the Fraser
      Health Authority in 2005, in response to evidence suggesting that having
      pharmacists provide care to patients in their homes after discharge from hospital
      could reduce subsequent utilization of health service resources. OBJECTIVE: To
      determine the effectiveness of the Medication Management Program in its first 2
      years of operation. METHODS: For patients who had received a home visit by a
      pharmacist, the utilization of health services (admissions to hospital, physician
      office visits, and dispensed medications) in the year before the home visit was
      compared with utilization during the year after the intervention. The net cost of
      the program was also determined. RESULTS: In the first 2 years of the Medication
      Management Program (2005/2006 and 2006/2007), a total of 1171 patients received a
      home visit from a pharmacist. Of these, 836 (71%) were included in the before-and
      after analysis. The median per-patient cost for utilization of health services
      was $11 014 lower in the year after the intervention than in the year preceding
      the intervention. After the costs of the program were taken into account, this
      resulted in a net median cost reduction of $3047.43 per patient. CONCLUSION: The
      Medication Management Program was effective as a clinical program in its first 2
      years.

PMID- 22479014
TI  - Use of milrinone in critically ill children.
AB  - BACKGROUND: Optimal dose adjustment of milrinone in critically ill children is
      challenging because of conflicting information about the association between dose
      and outcomes in this age group. OBJECTIVES: To describe the use of milrinone in
      critically ill children and to explore associations between milrinone dosing and
      clinical outcomes, specifically effectiveness and adverse events. METHODS: This
      retrospective cohort study was performed in a consecutive sample of children
      admitted to a university-affiliated critical care unit (January to June 2004).
      The relations between milrinone dosing and its effectiveness (based on prevention
      of low cardiac output syndrome, defined as a difference in oxygen saturation
      between arterial and mixed venous blood of at least 30% or an increase in serum
      lactate > 2 mmol/L) and its adverse effects (thrombocytopenia, arrhythmia) were
      evaluated by logistic regression. RESULTS: A total of 197 children from 213
      admissions (ranging in age from newborn to 18 years) were included in the study.
      Milrinone was initiated with a median loading dose of 99.2 MUg/kg (range 22.1
      162.2 MUg/kg). The initial loading dose was higher if given in the operating room
      rather than the Critical Care Unit (median 99.7 versus 51.0 MUg/kg; p < 0.001).
      Subsequent loading doses, for patients who received them, were lower (median 49
      MUg/kg). Milrinone was infused at a median rate of 0.64 MUg/kg per minute (range
      0.13-2.08 MUg/kg per minute) for a median of 43.1 h. There was no relation
      between serum creatinine level and the maintenance dose of milrinone (r2 <=
      0.0335). Low cardiac output syndrome was relatively frequent (166 [77.9%] of the
      213 admissions). There was a trend for occurrence of this syndrome in patients
      with greater average milrinone dose rate (odds ratio [OR] 8.21, 95% confidence
      interval [CI] 0.98-69.15, p = 0.053) and with longer duration of milrinone
      therapy (OR 1.01, 95% CI 1.01-1.02, p < 0.05). Adverse events were relatively
      frequent (thrombocytopenia for 27 admissions [12.7%], arrhythmia for 82
      admissions [38.5%]) but were not significantly associated with milrinone dosing.
      CONCLUSIONS: A retrospective evaluation of milrinone use in critically ill
      children revealed variable utilization and frequent occurrence of both low
      cardiac output syndrome and adverse events. Further prospective research is
      needed to understand the impact of individual pharmacokinetic differences on
      pharmacodynamic responses, to guide optimal dose adjustment, improve outcomes,
      and minimize toxic effects.

PMID- 22479015
TI  - Evaluating appropriateness of prescribing of long-acting risperidone for
      injection in acute care settings.
AB  - BACKGROUND: Long-acting risperidone for injection is a second-generation
      antipsychotic indicated for the treatment of schizophrenia and related psychotic
      disorders. It is a relatively new agent with pharmacokinetic and dosing
      properties unlike those of conventional long-acting antipsychotic drugs
      administered by injection. OBJECTIVE: To determine the proportion of patients for
      whom long-acting risperidone for injection was prescribed appropriately in acute
      care settings in the Fraser Health Authority of British Columbia, according to
      the following 4 criteria: approved indication for therapy, 2-week dosing
      intervals, dose increases no sooner than every 4 weeks, and initial overlap
      supplementation with another antipsychotic for at least 3 weeks. A variety of
      other variables, including documented approval under special authority from the
      provincial drug coverage program, length of hospital stay, initial dose of
      risperidone, and total number of doses, were assessed as secondary outcomes.
      METHODS: A chart review was conducted for all patients for whom therapy with long
      acting risperidone for injection was prescribed during stays in 8 acute care
      hospitals between July 1, 2007, and July 22, 2008. The appropriateness of
      prescribing was assessed according to the 4 prespecified criteria. RESULTS: Long
      acting risperidone for injection was prescribed for 116 patients during the study
      period, and 82 of these started therapy and were included in the evaluation. The
      primary outcome could not be assessed for 27 of these 82 patients, because they
      were discharged early, and data for some or all of the 4 criteria were not
      available. For 33 (60%) of the 55 remaining patients, long-acting risperidone for
      injection had been prescribed appropriately. In contrast, for 22 (40%) of the
      patients, prescription of risperidone was deemed inappropriate because of failure
      to meet at least 1 of the 4 criteria. Premature escalation of the dose and
      inadequate overlap with antipsychotic supplementation were the most common
      reasons for designation of the prescription as inappropriate. CONCLUSIONS:
      Opportunities exist to improve prescribing practices for long-acting risperidone
      for injection in acute care institutions in this health authority.

PMID- 22479016
TI  - Stability of Levothyroxine in Sodium Chloride for IV Administration.
AB  - BACKGROUND: Levothyroxine by IV administration is often prescribed in the
      intensive care unit for the management of potential solid organ donors, following
      declaration of brain death and provision of consent for organ donation. Published
      data on the stability of levothyroxine in IV solutions are limited. OBJECTIVE: To
      evaluate the physical compatibility and chemical stability, over a 24-h period,
      of 2 concentrations of levothyroxine in 0.9% sodium chloride with storage at room
      temperature and with exposure to or protection from light. METHODS: Levothyroxine
      solutions (0.4 MUg/mL and 2.0 MUg/mL) were prepared in 50-mL minibags of 0.9%
      NaCl and stored at room temperature (25 degrees C) with exposure to or protection
      from light. Samples were collected from each minibag at time 0 and after 0.5,
      1.0, 1.5, 2.0, 3.0, 4.0, 8.0, 12.0, and 24.0 h. The samples were analyzed in
      triplicate with a validated stability-indicating high-performance liquid
      chromatography method using ultraviolet detection. A solution was considered
      stable if it maintained 90% of its initial concentration of levothyroxine.
      Changes in colour, clarity, and pH were assessed to determine the physical
      compatibility of the solutions. RESULTS: All samples remained clear, colourless,
      and free of precipitate throughout the study, and there were no significant
      changes in pH. Based on the 95% confidence interval of the slope of the curve
      relating concentration to time determined by linear regression, solutions of
      levothyroxine with concentration 0.4 MUg/mL would maintain at least 90% of the
      initial concentration for 16.9 h with exposure to light and for 18.0 h if kept in
      the dark. Solutions of levothyroxine with concentration 2.0 MUg/mL would maintain
      at least 90% of the initial concentration for 6.5 h with exposure to light and
      for 12.0 h if kept in the dark, with 95% confidence. CONCLUSIONS:
      Extemporaneously prepared solutions of levothyroxine in 0.9% NaCl can be expected
      to remain stable for at least 6.5 h if stored without protection from light and
      at least 12 h if stored in the dark. Stability is related to concentration, with
      more dilute solutions having greater stability.

PMID- 22479018
TI  - Practice spotlight: pharmacist in a chronic kidney disease clinic.

PMID- 22479017
TI  - The Voice of Canada's Front-line Pharmacists: CSHP Survey of Non-management
      Pharmacists.

PMID- 22479019
TI  - Should a Process be Developed to Recognize "Pharmacy Practice Residency
      Equivalency" for Pharmacists with Substantial Clinical Experience Who Have Not
      Completed a Pharmacy Practice Residency?

PMID- 22479020
TI  - [Not Available].

PMID- 22479021
TI  - Enhancing pharmacy practice with technology: a utopian dream?

PMID- 22479022
TI  - Pharmacists: the guardians of safe medication use.

PMID- 22479023
TI  - Completeness of information sources used to prepare best possible medication
      histories for pediatric patients.
AB  - BACKGROUND: Medication reconciliation can reduce medication errors and mortality.
      With limited availability of clinical pharmacists, it is important to determine
      the resources that will yield the most complete information about a patient's
      medication history. OBJECTIVE: To identify the most time-efficient sources of
      information about medication history for use by clinicians in a pediatric care
      setting. METHODS: In July and August 2009, newly admitted pediatric patients
      (under 18 years of age) were identified, and a best possible medication history
      (BPMH) was compiled from the admission history in each patient's chart, a
      provincial prescription database, a community pharmacy record, and an "informed
      interview". Each individual source of information was compared with the BPMH and
      given a completeness score based on 3 pieces of information about each medication
      (name, dose, and frequency). RESULTS: Data were collected for 99 pediatric
      patients. Of these, 76 (77%) were taking at least one medication, and 49 (50%)
      were taking at least one prescription medication. Among patients who were taking
      at least one medication, the informed interview, based on background information
      from other sources, resulted in the most comprehensive medication history, with a
      median completeness score of 100% (interquartile range [IQR] 90% to 100%). The
      admission history had a median completeness score of 33% (IQR 4% to 56%), with
      documentation of dose and frequency lacking most frequently. Information from
      community pharmacies had a median completeness score of 67% (IQR 42% to 87%), but
      this source was available for only 24 of the 99 patients. The prescription
      database was the least complete source, with a median completeness score of 0%
      (IQR 0% to 37%). CONCLUSION: An informed interview by a trained professional
      resulted in the most complete medication history. Admission histories represented
      the next most complete source. The data from this study indicated a need for
      education on the performance of medication reconciliation that would emphasize
      the use of all available background information, documentation of dose and
      frequency for each medication, and inclusion of both over-the-counter and herbal
      products.

PMID- 22479024
TI  - Psychometric evaluation of a self-medication assessment tool in an elderly
      population.
AB  - BACKGROUND: Most community-dwelling older adults are engaged in medication self
      management activities. Deviation in these activities can lead to adverse outcomes
      for patients and an increased burden on the health care system. Successful
      medication self-management involves a complex interaction among cognitive,
      functional, and psychosocial variables. Several assessment instruments have been
      developed, but there remains a need for an effective and comprehensive tool.
      OBJECTIVE: To evaluate the psychometric properties (inter-rater reliability, test
      retest reliability, and validity), as well as the usability, of the Self
      Medication Assessment Tool (SMAT), an instrument designed to measure elderly
      patients' ability to manage their medications. METHODS: The study enrolled
      patients 65 years of age or older who were living independently and were admitted
      to family medicine beds in a community hospital in eastern Canada. Three
      subsamples of the population were identified. The inter-rater reliability group
      was videotaped and scored independently by 2 pharmacists. The test-retest
      reliability group was tested with the SMAT and was retested with the same tool a
      week later. The usability group was interviewed after using the SMAT to determine
      their satisfaction. Standard neuropsychological measures (Cognitive Competency
      Test, clock-drawing test, and Mini Mental State Examination [MMSE]) were used to
      determine convergent and divergent validity. Pill counts, refill rates, and use
      of adherence aids or reminders before study enrolment were used as measures of
      concurrent validity. RESULTS: A total of 121 patients (mean age 81.5 years) were
      enrolled. The scales of the SMAT were determined to have good internal
      consistency and high inter-rater and test-retest reliability. Convergent validity
      was evidenced by the high positive correlation between the functional scale of
      the SMAT and the results of the clock-drawing and Cognitive Competency tests (p <
      0.01) and between the cognitive and recall scales of the SMAT and the results of
      the clock-drawing test (p < 0.05), the MMSE (p < 0.01), and the Cognitive
      Competency Test (p < 0.01). Patients reported being highly satisfied with their
      experience. CONCLUSION: The SMAT is a practical, reliable, comprehensive
      instrument with demonstrated convergent validity, strong patient acceptability,
      and various internally consistent scales that assess multiple dimensions of
      elderly patients' ability to self-manage their medications. Further testing is
      required to show that the SMAT correlates with medication adherence.

PMID- 22479025
TI  - Review of prescribing practices for intermittent bolus administration of
      morphine.
AB  - BACKGROUND: Several changes to medication safety practices were proposed in a
      pediatric hospital, including changing the period of patient observation after
      administration of opioids and limiting the availability of various concentrations
      of morphine in the patient care unit. OBJECTIVE: To document and review
      postoperative pain management for children on a surgical ward, specifically with
      regard to intermittent IV bolus administration of morphine, to help in assessing
      the impact of the proposed nursing practice changes. METHODS: Data were collected
      from records for narcotics and controlled drugs for the surgical ward over a 3
      month period (April to June 2006). For each patient, data had been recorded for
      up to 7 consecutive days after surgery. A patient's data were included in the
      review if he or she had received at least 2 doses of morphine by IV bolus, except
      for the review of weight-based dosing pattern (mg/kg), for which all patients who
      had received at least one dose of IV morphine were included. RESULTS: Charts for
      193 patients were audited. Of these, 163 patients (84.5%) had recieved up to 0.1
      mg/kg per dose, and 53 (27.5%) had received only one dose of morphine. Among
      patients who received more than one dose, the median dose was 0.080 mg/kg on day
      1, with a decrease by day 5 to 0.065 mg/kg. Most patients received morphine over
      the first 2 days after surgery. The median time elapsed between doses was 4.3 h
      on day 1 and 6.2 h on day 2. Of the 1020 doses included in the analysis, most
      (801 [78.5%]) were 4 mg or less. CONCLUSION: The intermittent administration of
      IV bolus doses of morphine at the study hospital followed common standards for
      the treatment of postoperative pain. Most doses were no more than 4 mg. On the
      basis of this information, only 2-mg vials of morphine are now stocked on the
      ward. The hospital's change in monitoring practices will increase the
      surveillance of patients receiving IV bolus doses of morphine.

PMID- 22479026
TI  - Pharmacists' perceptions of their professional role: insights into hospital
      pharmacy culture.
AB  - BACKGROUND: Numerous studies have demonstrated the positive impacts of
      pharmacists on patient outcomes. To capitalize on these positive impacts,
      hospital pharmacy organizations around the world are now calling on pharmacists
      to shift their focus from distribution of medications to patient outcomes. This
      new emphasis is consistent with the vision statement for the profession of
      pharmacy in Canada, as set out in the Blueprint for Pharmacy: "Optimal drug
      therapy outcomes for Canadians through patient-centred care". Given the ambitious
      nature of this statement and these goals, it is essential to understand what
      pharmacists currently think of their practice. OBJECTIVE: To conduct a
      qualitative and semiquantitative analysis of hospital pharmacists' perceptions of
      their role in patient care. METHODS: A researcher posing as a University of
      Alberta student who was studying how health professionals use language to
      describe what they do contacted the pharmacy departments of all hospitals in
      Alberta. The "top-of-mind" approach was used in asking hospital pharmacists 2
      questions: (1) How many years have you been practising pharmacy? (2) In 3 or 4
      words (or phrases), from your perspective could you please tell me, "What does a
      pharmacist do"? These techniques were used to minimize the impact of social
      desirability bias. Content analysis was used to categorize hospital pharmacists'
      responses into 4 broad categories: patient-centred, drug-focused, drug
      distribution, and ambiguous. RESULTS: A total of 103 phone calls were made to
      hospital pharmacies, and 85 pharmacists contacted in this way were willing to
      participate in the survey. Hospital pharmacists provided 333 individual responses
      to the question about their activities. Of these, 79 (23.7%) were patient
      centred, 98 (29.4%) were drug-focused, and 82 (24.6%) were in the drug
      distribution category. Ambiguous responses accounted for the remaining 74
      (22.2%). CONCLUSION: Aspects of care categorized as other than patient-centred
      should not be construed as unimportant. However, the fact that they were reported
      in this survey more frequently than patient-centred aspects suggests that
      hospital pharmacists in Alberta may have not fully embraced the concept of
      patient-centred care as outlined in the Blueprint for Pharmacy.

PMID- 22479027
TI  - Use of oral bisphosphonates by older adults with fractures and impaired renal
      function.
AB  - BACKGROUND: The manufacturers of oral bisphosphonates (alendronate, risedronate)
      recommend avoiding use of these drugs in patients with renal impairment. However,
      many patients who have osteoporosis or who are at risk of fracture are elderly
      and may have renal impairment. This situation poses a quandary for clinicians in
      deciding how best to manage osteoporosis in this high-risk population. OBJECTIVE:
      To synthesize published evidence regarding the use and safety of oral
      bisphosphonates for patients with impaired renal function. METHODS: The following
      databases were searched up to October 2010: PubMed, MEDLINE, Embase, the Cochrane
      Library, and International Pharmaceutical Abstracts. The following key words and
      terms were used for the searches: bisphosphonates, alendronate, risedronate,
      Fosamax, Actonel, "renal failure", "renal insufficiency", "chronic kidney
      disease", and "end-stage renal disease". The manufacturers of Fosamax and Actonel
      were asked to provide information about use of their products in patients with
      renal impairment, including unpublished pharmacokinetic studies or reports of
      adverse drug events. RESULTS: The search yielded 2 post hoc analyses of safety
      data, 1 case-control study, 1 case series, 4 retrospective chart analyses, and 2
      prospective studies. According to these publications, numerous patients with
      decreased renal function have received bisphosphonates and have experienced
      improvement in bone mineral density and/or reduction in risk of fractures, with
      no increase in adverse effects. Increased renal damage occurred in some
      individuals with underlying renal disorders, as described in case reports.
      CONCLUSIONS: Although the literature is limited, there is evidence that
      alendronate and risedronate are well tolerated and effective when used by
      individuals with renal impairment. Further research is required to confirm the
      benefits and risks of using these medications in patients with renal impairment.

PMID- 22479028
TI  - Improving the quality of clinical pharmacy services: a process to identify and
      capture high-value "quality actions".

PMID- 22479029
TI  - Provision of pharmacy services at an influenza assessment centre.

PMID- 22479030
TI  - Practice spotlight: drug safety pharmacist.

PMID- 22479031
TI  - Should key performance indicators for clinical services be mandatory?

PMID- 22479033
TI  - Tribute to the reviewers of the canadian journal of hospital pharmacy.

PMID- 22479032
TI  - Are we ready to share data from pharmacy information systems to electronic health
      records?

PMID- 22479034
TI  - CSHP Professional Practice Conference 2011: Poster Abstracts / Conference sur la
      pratique professionnelle 2011 de la SCHP : Resumes des affiches.

PMID- 22479035
TI  - 2011 CSHP National Awards Program Winners.

PMID- 22479036
TI  - The year of the dog.

PMID- 22479037
TI  - Pharmacists unite!

PMID- 22479038
TI  - Toward a unified model for contemporary institutional pharmacy practice.

PMID- 22479040
TI  - A Pilot Comparative Study of the Clarity and Assessability of the Drug Management
      Standards of Accreditation Canada and the US Joint Commission.
AB  - BACKGROUND: There are few data comparing the drug management standards of the US
      and Canadian agencies that accredit health care institutions. OBJECTIVE: To
      evaluate the clarity and assessability of criteria in the drug management
      standards adopted by Accreditation Canada and the Joint Commission (United
      States). METHODS: A pilot study was conducted to compare the clarity and
      assessability of the criteria listed in the 2 standards. Criteria that were
      common to the 2008 versions of the Canadian and US drug management standards were
      identified. A panel of 12 health care professionals was assembled to
      independently rate the clarity (i.e., clear or unclear) and the assessability
      (i.e., assessable or not assessable) of each statement, using a validated
      comparative grid. RESULTS: In total, there were 143 Canadian standards and 103 US
      standards. Sixty-two (43%) of the 143 Canadian criteria could be directly paired
      with a US criterion, whereas 70 (68%) of the 103 US criteria could be paired with
      one or more Canadian criteria. Six of the US criteria were paired with more than
      one Canadian criterion, and 12 of the Canadian criteria could be paired with more
      than one US criterion. Four of the 22 themes in the Canadian standards had no
      equivalent criteria in the US standards. Panel members from the pharmaceutical
      practice group evaluated the clarity and assessability of the Canadian criteria
      more severely than panel members from the nursing practice group: 86% versus 95%
      of individual ratings were deemed "clear" by these two groups, respectively (p <
      0.001) and 64% versus 88% of individual ratings were deemed "assessable" (p <
      0.001). There were no criteria that were considered unclear or unassessable by
      all of the panel members. CONCLUSIONS: Few data are available on drug management
      standards and their impact on health care. A better understanding of these
      standards, as well as comparisons of Canadian standards with those of other
      countries, might help in determining their clarity and assessability. A larger
      scale study is required to validate the observations reported here.

PMID- 22479039
TI  - [Not Available].
AB  - CONTEXT: Few data are available on the use and consequences of decentralized
      automated dispensing cabinets (ADCs) in institutional settings. METHOD: This
      descriptive study examined compliance with published guidelines on the
      implementation of decentralized ADCs. The primary objective was to evaluate
      overall compliance, as well as compliance with specific steps in the medication
      cycle. The study was carried out at the Centre hospitalier universitaire (CHU)
      Sainte-Justine, a 500-bed mother-and-child hospital. The 2008 guidelines of the
      Institute for Safe Medication Practices (US) concerning the safe use of
      decentralized ADCs and the associated self-assessment tool (2009) were used to
      evaluate compliance at 30 days and at 120 days after implementation. RESULTS:
      From November 2009 to April 2010, 7 decentralized ADCs were brought into service
      at the CHU Sainte-Justine. Overall compliance with published guidelines increased
      from 66% to 74% between January and April 2010. For each process related to the
      safe use of the ADCs, the criteria were briefly described, along with the non
      compliance components related to technological or organizational aspects of
      implementation. For each component for which practice was noncompliant with
      guidelines, the actions required to modify the equipment (i.e., technological
      aspects) were determined and conveyed to the manufacturer; similarly, modes of
      use requiring modification (i.e., organizational aspects) were determined and
      conveyed to the institution. CONCLUSION: This study has described the compliance
      of practices at the CHU Sainte-Justine with published guidelines of the Institute
      for Safe Medication Practices. The use of published guidelines can help to guide
      both the technological and organizational aspects of implementing decentralized
      ADCs. [Publisher's translation].

PMID- 22479041
TI  - Developing, implementing, and evaluating a formal pharmacist mentorship program.
AB  - BACKGROUND: Mentoring is associated with positive professional and personal
      outcomes. However, there are few published data on mentoring programs for
      pharmacists. OBJECTIVE: To develop and evaluate a mentorship program for hospital
      pharmacists that was implemented at St Joseph's Healthcare Hamilton, in Hamilton,
      Ontario, by identifying the benefits and challenges that participants experienced
      and determining whether the program provided the necessary skills for a
      successful mentoring relationship. METHODS: A descriptive pilot study was
      performed between June 2007 and November 2008. Focus groups and self-administered
      questionnaires were conducted at two time points (after 3-4 months and at the end
      of the study period). The focus groups were conducted separately for mentors and
      mentees. Data were summarized by predefined categories. Quantitative data from
      the questionnaires were summarized as medians, minimums, and maximums, and
      qualitative survey data were transcribed and reviewed. RESULTS: Three mentors
      were each paired with a mentee. The mentees identified an average of 4 learning
      objectives. All of the mentees reported improvements in their self-perceived
      level of competency and skill within the mentoring relationship and their
      confidence in their ability to perform the functions of a hospital pharmacist.
      The job satisfaction of both mentors and mentees improved. Reported challenges
      were related to scheduling and documentation. Mentors and mentees reported high
      levels of overall satisfaction with the program, at both of the evaluation time
      points. Participants spent less than 60 min/week each on mentoring activities.
      CONCLUSIONS: Both mentors and mentees benefited from the mentoring relationship.

PMID- 22479043
TI  - Evaluation of anemia management by algorithms in patients with chronic kidney
      disease who are not receiving dialysis.
AB  - BACKGROUND: Anemia commonly develops in patients with chronic kidney disease and
      is strongly associated with adverse clinical outcomes. There are currently no
      published studies evaluating the efficacy of a nurse-driven anemia-management
      protocol for patients with chronic kidney disease who are not receiving dialysis.
      OBJECTIVES: To evaluate the efficacy of an anemia-management protocol in terms of
      achieving hemoglobin and transferrin saturation levels within the target range,
      as well as associated utilization of medications, relative to individualized
      dosing of medications by nephrologists. METHODS: An algorithm for nurse-driven
      management of anemia was introduced in April 2009 at a kidney function clinic in
      a large urban centre. The charts of patients with chronic kidney disease who were
      not undergoing dialysis were reviewed before (July to December 2007) and after
      (July to December 2009) implementation of the protocol. Patients' data for
      hemoglobin, transferrin saturation, and doses of iron and erythropoiesis
      stimulating agents were collected for each of the 6-month study periods. RESULTS:
      In total, 390 patients were treated for anemia before and 434 patients after
      introduction of the protocol. The anemia-management protocol was non-inferior to
      individualized dosing for maintenance of hemoglobin levels within the target
      range of 110-120 g/L: percentage of measured levels within target range 33.3%
      (485/1456) before versus 34.2% (504/1472) after (absolute difference 0.9
      percentage points, 95% confidence interval [CI] -2.5 to 4.4). The criteria for
      non-inferiority were not met for maintenance of transferrin saturation within the
      target range of 22%-50%: percentage of levels within target range 58.8% (374/636)
      before versus 56.9% (403/708) after (absolute difference 1.9 percentage points,
      95% CI -3.4 to 7.2). There were no statistically significant differences in mean
      doses of epoetin alfa, darbepoetin, or iron before and after introduction of the
      protocol. Similarly, there were no statistically significant differences in
      number of dose changes for epoetin alfa, darbepoetin, or iron. CONCLUSION: The
      nurse-driven anemia-management protocol was non-inferior to dosing by
      nephrologists in terms of managing hemoglobin levels. It would be reasonable to
      use an anemia-management protocol for patients with chronic kidney disease who
      are not receiving dialysis.

PMID- 22479044
TI  - Practice spotlight: pharmacist in a family medicine teaching unit.

PMID- 22479042
TI  - Coping strategies used by patients infected with hepatitis C virus who are facing
      medication costs.
AB  - BACKGROUND: The prevalence of infection with hepatitis C virus (HCV) is
      increasing worldwide. Antiviral therapy, prescription and nonprescription
      medications, and nondrug therapies to treat HCV infection and to manage
      associated adverse effects are costly. OBJECTIVE: To determine whether
      individuals infected with HCV attending a hepatology clinic were negatively
      affected by the costs of prescription medications, and if so, to determine coping
      strategies they adopted. METHODS: Patients infected with HCV attending Hepatology
      Services, a clinic within the Queen Elizabeth II Health Sciences Centre in
      Halifax, Nova Scotia, were interviewed as part of an exploratory study (April 2
      to July 8, 2008). The interview was based on a validated survey adapted for Nova
      Scotia. Information collected included demographic characteristics; types of
      prescription, nonprescription, and complementary medications used by patients;
      and strategies patients adopted to pay their medication costs. RESULTS: Fifty
      patients (age 33-64 years) participated in the interviewer-administered survey,
      including 35 (70%) men and 19 people (38%) with household income less than $30
      000. Frequently used medications were antidepressants (19 patients [38%]),
      antihypertensive agents (12 [24%]), anxiolytics (10 [20%]), and nonsteroidal anti
      inflammatory drugs (10 [20%]). More than half (29 [58%]) were concerned about
      having sufficient money to pay for their medications. Coping strategies adopted
      in response to costs of prescription medications were either self-initiated or
      undertaken in consultation with physicians and/or other health care
      professionals. Sixteen (32%) of the respondents expressed the belief that
      physicians usually do not consider patients' concerns about affordability when
      prescribing medications. Seven (14%) indicated they would seek help from a
      pharmacist to buy low-cost substitutes for their medications. CONCLUSION: This
      study highlighted a range of coping strategies adopted by patients infected with
      HCV in response to medication costs. It underscores that cost may limit access to
      essential medications within this patient population, even in a publicly funded
      health care system. Some of the coping strategies adopted might reduce patients'
      persistence and adherence with medication therapy, which could lead to adverse
      health outcomes. Hospital and community pharmacists need to be aware of the
      challenges faced by patients in terms of paying for medications and should
      consider possible proactive responses to address potentially detrimental coping
      strategies.

PMID- 22479045
TI  - Should erythropoiesis-stimulating agents be used in predialysis patients?

PMID- 22479046
TI  - The "con" side.

PMID- 22479047
TI  - What is Pharmacy Research?

PMID- 22479048
TI  - Current-oasis: a potential mirage of numbers.

PMID- 22479049
TI  - Pediatric pharmacokinetics of vancomycin: a canadian perspective.

PMID- 22479050
TI  - Society news/nouvelles de la societe.

PMID- 22479051
TI  - Ghosts of pharmacy past, present, and future.

PMID- 22479052
TI  - Free the pharmacist!

PMID- 22479053
TI  - Extended-interval aminoglycoside therapy for adult patients with febrile
      neutropenia: a systematic review.
AB  - BACKGROUND: Although the efficacy and toxicity of extended-interval (once-daily)
      aminoglycoside regimens is well established for immunocompetent patients, there
      is clinical concern about using this regimen for patients with neutropenia.
      OBJECTIVE: To summarize and evaluate the literature reporting the clinical
      efficacy and safety of extended-interval aminoglycosides therapy in adults with
      febrile neutropenia. METHODS: A literature search was conducted within PubMed,
      Embase, and the Cochrane Database of Systematic Reviews to identify studies
      assessing the use of extended-interval aminoglycosides for treating febrile
      neutropenia in adults. Articles were categorized by quality of evidence,
      according to the rating scale of the US Preventive Services Task Force. RESULTS:
      TEN ARTICLES WERE IDENTIFIED: 5 with level I evidence, 1 with level II-2
      evidence, and 4 with level III evidence. Review of the 5 studies with level I
      evidence (all open-label randomized controlled trials), which compared extended
      interval dosing with multiple-daily dosing strategies, revealed no evidence to
      suggest superiority of one regimen over the other in terms of clinical outcomes.
      In the study with level II-2 evidence (a prospective comparative trial), the
      response rate was better in the extended-interval group than in the standard
      therapy group. Two of the studies with level III evidence (both prospective
      noncomparative trials) also had acceptable response rates to extended-interval
      aminoglycoside therapy, with minimal associated nephrotoxicity. In this review,
      no major differences in rates of nephrotoxicity or ototoxicity were seen between
      the 2 dosing regimens. CONCLUSIONS: The use of extended-interval dosing for
      aminoglycosides, in combination with other recommended antibiotic therapy, is an
      effective and safe management strategy for immunocompromised patients with
      febrile neutropenia. In this population, the clinical efficacy and safety of
      extended-interval dosing does not appear to differ from those of standard dosing.
      Whether routine or selective pharmacokinetic monitoring in this patient
      subpopulation leads to improvements in outcomes is yet to be determined.

PMID- 22479054
TI  - Stability of pantoprazole sodium in glass vials, polyvinyl chloride minibags, and
      polypropylene syringes.
AB  - BACKGROUND: Pantoprazole sodium, a proton-pump inhibitor, is approved for the
      short-term treatment of several types of ulcer, Zollinger-Ellison syndrome, and
      gastroesophageal reflux disease. OBJECTIVE: To determine the physical
      compatibility and chemical stability of ethylenediaminetetra-acetic acid (EDTA)
      free pantoprazole in glass vials, polypropylene syringes, and polyvinylchloride
      (PVC) minibags, after storage at 2 degrees C to 8 degrees C with protection from
      light or at 20 degrees C to 25 degrees C with exposure to light. METHODS:
      Solutions of pantoprazole 4 mg/mL reconstituted in 0.9% sodium chloride (normal
      saline [NS]) were stored in glass vials at 20 degrees C to 25 degrees C. Similar
      solutions were transferred to polypropylene syringes and stored at 2 degrees C to
      8 degrees C. Stock solution was further diluted, in 5% dextrose in water (D5W) or
      NS, to 0.4 or 0.8 mg/mL, and samples were then packaged in PVC minibags for
      storage at 2 degrees C to 8 degrees C or at 20 degrees C to 25 degrees C. Samples
      collected on days 0, 2, 3, 7, 14, 21, and 28 were analyzed in duplicate with a
      stability-indicating high-performance liquid chromatography assay. RESULTS:
      Pantoprazole 4 mg/mL was stable (i.e., retained at least 90% of initial
      concentration) for 3 days when stored in glass vials at 20 degrees C to 25
      degrees C or for 28 days when stored in polypropylene syringes at 2 degrees C to
      8 degrees C. Pantoprazole 0.4 mg/mL diluted in D5W and stored in PVC minibags was
      stable for 2 days at 20 degrees C to 25 degrees C or for 14 days at 2 degrees C
      to 8 degrees C. At 0.8 mg/mL, pantoprazole in D5W was stable for 3 days at 20
      degrees C to 25 degrees C or 28 days at 2 degrees C to 8 degrees C. Pantoprazole
      diluted to either 0.4 or 0.8 mg/mL in NS and stored in PVC minibags was stable
      for 3 days at 20 degrees C to 25 degrees C or 28 days at 2 degrees C to 8 degrees
      C. CONCLUSIONS: The present study confirmed or extended previously reported
      expiry dates for pantoprazole sodium packaged in glass vials, polypropylene
      syringes, and PVC minibags.

PMID- 22479055
TI  - Development and evaluation of a checklist for medication order review by
      pharmacists.
AB  - BACKGROUND: To create a checklist of the tasks that a pharmacist must perform
      during medication order review in the hospital setting and to evaluate the
      utility of and pharmacists' satisfaction with the checklist. METHODS: An evidence
      based checklist for medication order review was developed, with items related to
      order urgency, verification of patients' identity, therapeutic review, and
      actionable items. Pharmacists were educated about the checklist, and it was made
      available at 2 community hospitals in an urban setting. Pharmacists completed a
      nonvalidated satisfaction survey and participated in focus groups or interviews
      within 3 months after implementation of the checklist. Qualitative descriptive
      theory was used to identify themes within the data. Near-miss occurrence reports
      for the 3 months before and after implementation of the checklist were
      quantified. RESULTS: Of 16 pharmacists who were involved in the implementation
      phase, 14 participated in focus groups or an interview, and 11 responded to the
      survey. All respondents felt that the primary role of the checklist was for
      training. They felt that the checklist could be useful when reviewing high-alert
      or unfamiliar medications or therapy for patients with complex medications. The
      checklist was most helpful when it was used as a reminder, on an as-needed basis.
      Nine (82%) of the 11 survey respondents indicated that the checklist standardized
      the process of medication order review, the same number felt that it prevented
      accidental omission of critical checks, and 8 (73%) felt that it improved patient
      safety. Education was necessary to reinforce the purpose of the checklist and its
      self-check nature. There was no difference in the number of near misses in the
      pharmacy between the 3-month periods before and after implementation of the
      checklist. CONCLUSION: Pharmacists participating in the study felt that a
      checklist for medication order review had a role in training new pharmacists and
      standardizing processes.

PMID- 22479056
TI  - Stability of levetiracetam in extemporaneously compounded suspensions.
AB  - BACKGROUND: Levetiracetam is widely used as adjunctive therapy in the treatment
      of partial-onset seizures, myoclonic seizures, primary generalized tonic-clonic
      seizures, and idiopathic generalized epilepsy in the community and in hospital.
      However, no convenient, easy-to-swallow dosage form is commercially available in
      Canada. Moreover, no stability data are available for this antiepileptic prepared
      in a vehicle combining Ora-Sweet sweetener and Ora-Plus suspending agent.
      OBJECTIVE: To evaluate the stability of levetiracetam suspensions in amber
      plastic bottles at room temperature and under refrigeration for up to 91 days.
      METHODS: Suspensions of levetiracetam (50 mg/mL) were prepared in a 1:1 mixture
      of Ora-Sweet sweetening agent and Ora-Plus suspending agent. The suspensions were
      transferred to 50-mL amber plastic prescription bottles, which were stored at 25
      degrees C or at 4 degrees C. Samples were collected from each bottle at time zero
      and on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, and 91. The samples
      were analyzed in triplicate by a validated, stability-indicating high-performance
      liquid chromatography method with ultraviolet detection. A suspension was
      considered stable if it maintained at least 90% of its initial concentration of
      levetiracetam. Colour, odour, taste, clarity, and pH were assessed to determine
      physical compatibility. RESULTS: All samples remained physically unchanged over
      time, and there was no significant change in pH. The 95% confidence interval of
      the slope of the curve relating concentration to time, determined by linear
      regression, indicated that suspensions stored at 25 degrees C would maintain at
      least 91.4% of the initial levetiracetam concentration for 91 days and that
      suspensions stored at 4 degrees C would maintain at least 93.2% of the initial
      concentration for 91 days, with 95% confidence. CONCLUSION: Levetiracetam
      suspensions prepared in Ora-Sweet/Ora-Plus vehicle and stored in plastic
      prescription bottles at either 25 degrees C or 4 degrees C can be expected to
      remain stable for 91 days.

PMID- 22479058
TI  - Practice spotlight: compounding pharmacy.

PMID- 22479057
TI  - Tracking required organizational practices related to processes involving
      medications.

PMID- 22479059
TI  - Should Pharmacy Technician Managers Be Responsible for the Drug Distribution
      System within Hospital Pharmacy Departments?

PMID- 22479060
TI  - Use of commercially available heparin solution for neonates.

PMID- 22479061
TI  - Integrating a pharmacist into an already-established primary health care team.

PMID- 22479063
TI  - What My 1-Year-Old Son Has Taught Me about Pharmacist Practice.

PMID- 22479062
TI  - Sharing data from pharmacy information systems.

PMID- 22479064
TI  - Of silos and systems: the issue of regionalizing health care.

PMID- 22479065
TI  - Stability of cefazolin sodium in polypropylene syringes and polyvinylchloride
      minibags.
AB  - BACKGROUND: Cefazolin is a semisynthetic penicillin derivative with a narrow
      spectrum of activity covering some gram-positive organisms and a few gram
      negative aerobic bacteria. OBJECTIVE: To determine the physical and chemical
      stability of cefazolin sodium reconstituted with sterile water for injection and
      stored in polypropylene syringes or diluted with either 5% dextrose in water
      (D5W) or 0.9% sodium chloride (normal saline [NS]) and stored in
      polyvinylchloride (PVC) minibags. METHODS: Reconstituted solutions of cefazolin
      (100 or 200 mg/mL) were packaged in polypropylene syringes. More dilute solutions
      (20 or 40 mg/mL) were prepared in D5W or NS and packaged in PVC minibags. For
      each concentration-diluent-container combination, 3 containers were designated
      for each day of analysis (days 7, 14, 21, and 30). Containers were stored under
      refrigeration (5 degrees C) with protection from light until the designated day
      of analysis, at which time one 5-mL sample was collected from each the designated
      container. The designated containers were then stored at room temperature (21
      degrees C to 25 degrees C) with exposure to light for an additional 72 h, and
      additional samples were drawn. The samples were assayed using a validated,
      stability-indicating high-performance liquid chromatography method. The colour
      and clarity of the solutions, as well as their pH, were also monitored on each
      sampling day. RESULTS: All samples remained clear for the duration of the study;
      they had a slight yellow colour that darkened over time, and there was an
      increase in pH. Solutions diluted with sterile water for injection and stored in
      polypropylene syringes retained at least 94.5% of the initial concentration after
      30 days of refrigerated storage and at least 92.1% after an additional 72 h at
      room temperature with exposure to light. Samples diluted in D5W or NS and stored
      in PVC minibags retained at least 95.8% of the initial concentration after 30
      days of refrigerated storage and at least 91.8% after an additional 72 h at room
      temperature with exposure to light. CONCLUSIONS: Cefazolin at various
      concentrations stored in polypropylene syringes or PVC minibags was stable for up
      to 30 days with storage at 5 degrees C with protection from light, followed by an
      additional 72 h at 21 degrees C to 25 degrees C with exposure to light.

PMID- 22479066
TI  - Avoiding Potential Medication Errors Associated with Non-intuitive Medication
      Abbreviations.
AB  - BACKGROUND: Pharmaceutical companies use a variety of abbreviations to denote
      short- and long-acting medications. Errors involving the administration of these
      medications are frequently reported. OBJECTIVES: To evaluate comprehension rates
      for abbreviations used to denote short- and long-acting medications and to
      evaluate whether changes to medication labels could reduce potential errors in
      the selection and administration of medications. METHODS: In phase 1 of the
      study, nursing staff were asked to define 4 abbreviations and then to categorize
      them by release rate. In phase 2, a simulation exercise, nursing staff were asked
      if it would be appropriate to administer a medication illustrated in a photograph
      (oxycodone CR 5-mg blister pack) on the basis of information highlighted in a
      screen shot of an electronic medication administration record (order for
      oxycodone 5 mg). Three different presentations were used to identify the
      medication in the medication administration record and on the drug label.
      RESULTS: In phase 1, 10 (28%) of 36 nursing staff members knew what all 4
      abbreviations meant, and 14 (39%) correctly classified all 4 abbreviations as
      indicating a short- or a long-acting medication. In the simulation exercise
      (phase 2), labelling changes reduced the likelihood of a potential medication
      administration error. CONCLUSIONS: Most abbreviations used to indicate short-
      versus long-acting medications were not correctly understood by study
      participants. Of more concern was the incorrect interpretation of some
      abbreviations as indicating the opposite release rate (e.g., "ER" interpreted as
      meaning "emergency release", rather than "extended release", with incorrect
      classification as a short-acting medication). This evaluation highlighted the
      potential consequences of using non-intuitive abbreviations to differentiate high
      risk medications having different release rates.

PMID- 22479067
TI  - Stability of ciprofloxacin in polyvinylchloride minibags.
AB  - BACKGROUND: Ciprofloxacin is a fluoroquinolone antibiotic used to treat
      infections caused by both gram-positive and gram-negative organisms. OBJECTIVE:
      To determine the physical and chemical stability of ciprofloxacin diluted in 5%
      dextrose in water (D5W) or 0.9% sodium chloride (normal saline [NS]) and stored
      in polyvinylchloride (PVC) minibags at various temperatures. METHODS: Solutions
      of ciprofloxacin (1 and 2 mg/mL) were prepared by diluting a commercially
      available concentrate (10 mg/mL) with either D5W or NS. The prepared solutions
      were then packaged in PVC mini-bags. Three minibags of each concentration-diluent
      combination were stored at 2 degrees C to 8 degrees C with protection from light,
      at 21 degrees C to 24 degrees C with exposure to light, and at 29 degrees C to 31
      degrees C with protection from light. Samples were collected from each minibag on
      days 0, 7, 14, and 30 and then analyzed. Colour, clarity, and pH were monitored
      when the samples were collected. On each day of analysis, the samples were
      accurately diluted before duplicate analysis with a stability-indicating high
      performance liquid chromatography assay. A solution was considered stable if the
      concentration remained above 90% of the initial values. RESULTS: There were no
      changes in the physical characteristics of any of the solutions. At both
      concentrations (1 and 2 mg/mL), the ciprofloxacin solutions prepared in D5W
      remained above 93.9% of the initial concentration over the 30-day study period
      under all 3 storage conditions. Similarly, at both concentrations, solutions
      diluted in NS remained above 95.9% of the initial concentration over the 30-day
      study period under all 3 storage conditions. CONCLUSIONS: Ciprofloxacin prepared
      in either D5W or NS and stored in PVC minibags was stable for 30 days under 3
      separate storage conditions: 2 degrees C to 8 degrees C with protection from
      light, 21 degrees C to 24 degrees C with exposure to light, and 29 degrees C to
      31 degrees C with protection from light.

PMID- 22479068
TI  - A pilot study of bar codes in a canadian hospital.
AB  - BACKGROUND: In 2004, the US Food and Drug Administration issued a new rule
      requiring most prescription and some over-the-counter pharmaceutical products to
      carry bar codes down to the level of individual doses, with the intent of
      reducing the number of medication errors. Despite these regulatory changes in the
      United States, Health Canada has not yet adopted any mandatory bar-coding of
      drugs. OBJECTIVE: To evaluate the feasibility of using commercial bar codes for
      receipt and preparation of drug products and to evaluate the readability of the
      bar codes printed on various levels of drug packaging. METHODS: This cross
      sectional observational pilot study was conducted in the Pharmacy Department of a
      Canadian mother-child university hospital centre in July 2010. For the purposes
      of the study, research drugs and cytotoxic drugs in various storage areas, as
      well as locally compounded medications with bar codes generated in house, were
      excluded. For all other drug products, the presence or absence of bar codes was
      documented for each level of packaging, along with the trade and generic names,
      content (i.e., drug product), quantity of doses or level of packaging,
      therapeutic class (if applicable), type of bar code (1- or 2-dimensional
      symbology), alphanumeric value contained in the bar code, standard of reference
      used to generate the alphanumeric value (Universal Product Code [UPC], Global
      Trade Item Number [GTIN], or unknown), and readability of the bar codes by 2
      scanners. RESULTS: Only 33 (1.9%) of the 1734 products evaluated had no bar codes
      on any level of packaging. Of the 2875 levels of packaging evaluated, 2021
      (70.3%) had at least one bar code. Of the 2384 bar codes evaluated, 2353 (98.7%)
      were linear (1-dimensional) and 31 (1.3%) were 2-dimensional. Well over three
      quarters (2112 or 88.6%) of the evaluated bar codes were readable by at least 1
      of the 2 scanners used in the study. CONCLUSIONS: On the basis of these results,
      bar-coding could be used for receipt of 80.9% of the drug products at this
      Canadian hospital and for the preparation and dispensing of 70.1% of the
      products.

PMID- 22479069
TI  - Nitrofurantoin-associated lung and liver toxicity leading to liver
      transplantation in a middle-aged patient.

PMID- 22479070
TI  - Phenytoin-induced reduction in sirolimus levels.

PMID- 22479072
TI  - Practice spotlight: "reaching new heights" in pharmaceutical care at altum
      health.

PMID- 22479071
TI  - [Not Available].

PMID- 22479073
TI  - Is a single provincial pharmacy program beneficial for the advancement of
      pharmacy practice?

PMID- 22479074
TI  - Stability of buffered lidocaine in glass vials.

PMID- 22479075
TI  - Recent data from the canadian hospital pharmacy residency matching service.

PMID- 22479076
TI  - [Not Available].

PMID- 22479077
TI  - Home inotrope program for patients with end-stage heart failure awaiting heart
      transplant.

PMID- 22479078
TI  - Effect of albumin on phenytoin concentration: are we flogging a dead horse?

PMID- 22479079
TI  - Is there an app for that?

PMID- 22479080
TI  - The Role of Self-Compassion in Development: A Healthier Way to Relate to Oneself.

PMID- 22479081
TI  - In utero Repair of Myelomeningocele: Rationale, Initial Clinical Experience and a
      Randomized Controlled Prospective Clinical Trial.
AB  - Myelomeningocele (MMC), one of the most common congenital malformations, can
      result in severe lifelong disabilities, including paraplegia, hydrocephalus,
      Arnold-Chiari II malformation, incontinence, sexual dysfunction, skeletal
      deformations, and mental impairment. MMC was the first nonlethal anomaly to be
      treated by fetal surgery. Studies in animals provide compelling evidence that the
      primary cause of the neurological deficit associated with MMC is not simply
      incomplete neurulation but rather chronic mechanical injury and amniotic-fluid
      induced chemical trauma that progressively damage the exposed neural tissue
      during gestation. Initial results suggest that the surgical repair of MMC before
      25 weeks of gestation may preserve neurological function, reverse the hindbrain
      herniation of the Arnold-Chiari II malformation, and obviate the need for
      postnatal placement of a ventriculoperitoneal shunt. As it is currently unknown
      whether fetal surgery for MMC is truly beneficial compared to standard postnatal
      care, a randomized, controlled clinical trial has been initiated within the
      United States.

PMID- 22479082
TI  - Growing a "positive culture" of antimicrobial stewardship in a community
      hospital.
AB  - BACKGROUND: Promoting the appropriate use of antimicrobials is a core value of
      antimicrobial stewardship. Prospective audit and feedback constitute an effective
      strategy for reducing the cost and use of antimicrobials, as well as their
      adverse effects, such as infection with Clostridium difficile. OBJECTIVE: To
      evaluate the antimicrobial stewardship program in the intensive care unit at the
      authors' hospital, in order to determine the cost and utilization of
      antimicrobials, as well as the rate of nosocomially acquired C. difficile
      infection. METHODS: An infectious diseases team, consisting of a physician and a
      pharmacist, performed prospective audit and feedback during a pilot study (April
      to June 2010). The team met with the intensive care unit team daily to discuss
      optimization of therapy. The cost and utilization of antimicrobial drugs, as well
      as rates of C. difficile infection, were compared between the pilot period and
      the same period during the previous year (April to June 2009). For 3 months after
      the pilot phase (i.e., July to September 2010), the strategy was continued 3 days
      per week. RESULTS: AFTER INTRODUCTION OF THE ANTIMICROBIAL STEWARDSHIP PROGRAM,
      THERE WAS A SIGNIFICANT REDUCTION IN THE COST OF ANTIMICROBIAL DRUGS: $27 917
      less than during the same period in the previous year, equivalent to a reduction
      of $15.45 (36.2%) per patient-day ($42.63 versus $27.18). Utilization of broad
      spectrum antipseudomonal antimicrobial agents was also significantly lower,
      declining from 63.16 to 38.59 defined daily doses (DDDs) per 100 patient-days
      (reduction of 38.9%). After the pilot period, the rate declined further, to 28.47
      DDDs/100 patient-days. During the pilot period, there were no cases of C.
      difficile infection, and in the post-pilot period, there was 1 case (overall rate
      0.42 cases/1000 patient-days). This rate was lower than (but not significantly
      different from) the rate for April to September 2009 (1.87 cases/1000 patient
      days). There were no differences in mortality rate or severity of illness.
      CONCLUSION: The antimicrobial stewardship program in this community hospital was
      associated with significant decreases in antimicrobial costs and in utilization
      of antipseudomonal antimicrobial agents and a nonsignificant decrease in the rate
      of C. difficile infection. Knowledge exchange, peer-to-peer communication, and
      decision support, key factors in this success, will be applied in implementing
      the antimicrobial stewardship program throughout the hospital.

PMID- 22479083
TI  - Medications prescribed and occurrence of falls in general medicine inpatients.
AB  - BACKGROUND: Although falls are multifactorial, medications are a key risk factor
      that may be modifiable. Falls were among the most common occurrences entered into
      a risk identification system at the authors' hospital. OBJECTIVES: To identify
      whether general medicine inpatients who had experienced a fall were taking any
      medications known to be associated with falls. METHODS: The literature was
      reviewed to develop a list of high-risk medications that have been associated
      with falls. In a retrospective quality-improvement database-based study,
      information from the risk identification system was merged with data from the
      pharmacy dispensing system for general medicine inpatients who had experienced a
      fall. The primary end point was the percentage of patients with a documented fall
      who had a prescription for a high-risk medication. The number of such medications
      that had been prescribed for patients who fell was also calculated. RESULTS:
      Eighty-one unique medications were found to be associated with falls. During the
      study period (April 1, 2008, to March 31, 2009), 151 patients experienced a fall.
      Of those, 144 (95.4%) were taking at least one high-risk medication. The mean
      number of high-risk medications per patient who experienced a fall was 2.2. Of
      all documented falls, a new high-risk medication had been started within 7 days
      before the fall for 74 (49.0%) and within 24 h before the fall for 17 (11.3%).
      The most commonly prescribed drugs during all time periods (i.e., within 24 h or
      7 days before the fall or since the patient's admission) were lorazepam and
      zopiclone. The pharmacy database did not track administration of medications, so
      it is possible that some of the drugs prescribed were not actually taken by the
      patient. CONCLUSION: Almost all inpatients who experienced a fall during the
      hospital stay had a prescription for at least one medication associated with a
      high risk for falls. Lorazepam and zopiclone were the drugs most commonly
      associated with falls in this hospital, and their use should be reviewed.

PMID- 22479084
TI  - Pilot Evaluation of Dermal Contamination by Antineoplastic Drugs among Hospital
      Pharmacy Personnel.
AB  - BACKGROUND: It is believed that health care workers are exposed to antineoplastic
      drugs primarily via dermal contact. However, levels of occupational dermal
      contamination in Canada have not been formally investigated. OBJECTIVE: To
      determine the potential dermal exposure to antineoplastic drugs among hospital
      pharmacy personnel in a metropolitan area in British Columbia. METHODS: Six
      hospital pharmacies in the Vancouver area participated in this pilot study. Three
      pharmacy workers (a technician responsible for preparing drugs, a pharmacist
      responsible for checking drugs before administration, and a technician not
      responsible for preparing drugs but working in the pharmacy department) were
      selected from each site, for a total of 18 participants. Each worker's hands were
      wiped with a premoistened tissue (one wipe per person), and the wipes were
      subsequently analyzed by high-performance liquid chromatography tandem mass
      spectrometry to determine levels of both cyclophosphamide and methotrexate (total
      of 36 analyses). RESULTS: At 3 of the 6 sites, at least one hand-wipe sample was
      above the analytical detection limit. Of the 18 analyses from the 3 "positive"
      sites, 5 (28%) had measurable levels of cyclophosphamide and methotrexate.
      Cyclophosphamide was detected in 3 samples (geometric mean 0.98 ng, geometric
      standard deviation 2.72 ng, range from below limit of detection to 3.96 ng) and
      methotrexate in 2 samples (geometric mean 0.27 ng, geometric standard deviation
      2.57 ng, range from below limit of detection to 0.27 ng). CONCLUSIONS: The
      results of this pilot study suggest that hospital pharmacy workers in Metro
      Vancouver are probably exposed to antineoplastic drugs, given that detectable
      levels of drug were found on the hands of some personnel. Further studies are
      recommended to confirm these findings.

PMID- 22479085
TI  - Implementation of the glucommander method of adjusting insulin infusions in
      critically ill patients.
AB  - BACKGROUND: Intensive glycemic control has been associated with reduced morbidity
      and mortality in critically ill patients. Web-based, patient-specific insulin
      nomograms may facilitate improved glucose control. OBJECTIVE: To compare 2
      algorithms for individualizing insulin infusion therapy (a web-based system
      [Glucommander method] and a standard paper-based nomogram) in a cardiovascular
      surgery intensive care unit (ICU). METHODS: In this prospective, before-after
      cohort study, measures of glycemic control for 50 patients receiving insulin
      according to the Glucommander system were compared with a control group (n = 50)
      who received insulin according to the standard paper-based nomogram used in the
      cardiovascular surgery ICU. RESULTS: There was no significant difference between
      the 2 groups with respect to time to target blood glucose (5.1-8.0 mmol/L),
      percentage of time within the target range, or mean amplitude of glucose
      excursion. Patients in the intervention group spent less time above the target
      range (p = 0.007) and more time below the target range (p < 0.001), and the mean
      glucose was lower in this group compared with the control group (7.9 versus 8.6
      mmol/L, p = 0.002). The percentage of blood glucose measurements below 4 mmol/L
      was higher in the intervention group than in the control group (3.7% versus 1.4%,
      p = 0.003). Satisfaction surveys revealed that the program was well accepted by
      the nursing staff in the cardiovascular surgery ICU. CONCLUSIONS: A web-based
      insulin nomogram was an easy-to-use instrument for achieving tighter glucose
      control for patients in the cardiovascular surgery ICU. Use of the Glucommander
      system led to lower mean blood glucose but an increase in episodes of
      hypoglycemia.

PMID- 22479086
TI  - Describing Intravenous Extravasation in Children (DIVE Study).
AB  - BACKGROUND: Extravasation, the inadvertent leakage of intravenous (IV) medication
      from the vein into the surrounding tissue, is a iatrogenic cause of patient
      injury. Extravasation has been reported to occur in 0.1% to 6.5% of hospital
      inpatients. The incidence may be higher among children because they have multiple
      risk factors, including small and fragile veins, decreased peripheral
      circulation, capillary leakage, and flexible subcutaneous tissue. OBJECTIVES: To
      describe the incidence of extravasation at a pediatric tertiary care hospital, to
      identify the agents causing extravasation, and to describe the use of antidotes
      to manage identified cases. A secondary objective was to describe adverse drug
      effects associated with the antidotes administered. METHODS: The medical records
      of pediatric patients with documented extravasation of an IV medication between
      January 1, 2006, and August 31, 2008, were analyzed retrospectively. The
      appropriateness of antidote use was determined in terms of adherence to the
      institution's protocol for treatment of extravasation. RESULTS: A total of 42
      patients had documented extravasation, for an overall incidence of 0.04% per
      patient-day. Of the 40 cases in which location was documented, 12 (30%) occurred
      on the general pediatric wards, 10 (25%) on the surgical ward, 9 (22%) in the
      neonatal intensive care unit, 5 (12%) in the pediatric intensive care unit, 3
      (8%) in day care, and 1 (2%) in the emergency department. The most common
      medications involved were fluids for IV administration (18 [43%]), potassium
      chloride (11 [26%]), antibiotics (8 [19%]), total parenteral nutrition (8 [19%]),
      calcium chloride (2 [5%]), and epinephrine (2 [5%]). Multiple drugs were involved
      in some cases of extravasation. The decision to administer an antidote and the
      choice of antidote (if required) were appropriate in 50% of the cases. No adverse
      drug effects were reported with use of antidotes. CONCLUSIONS: The incidence of
      extravasation was low. The medications most commonly involved were similar to
      those reported in the literature. Antidotes were well tolerated but were
      appropriately used in only half of the events. Prospective trials are needed to
      determine the clinical severity of injury and to assess the effectiveness and
      safety of antidotes.

PMID- 22479087
TI  - Retrospective audit of medication order turnaround time after implementation of
      standardized definitions.
AB  - BACKGROUND: Standardizing the interpretation of "stat", "emergent", "urgent", and
      "now" medication orders can improve patient safety. However, the effect of
      implementing standardized definitions on the turnaround time for medication
      orders in hospital pharmacy dispensaries has not been studied. OBJECTIVES: To
      examine the effects of using formal definitions for "stat", "emergent", "urgent",
      and "now" on turnaround time for medication orders within a pharmacy dispensary.
      METHODS: Definitions for "stat", "emergent", "urgent", and "now" orders, as well
      as for "turnaround time", were developed from the formal literature and the grey
      literature. The definitions were implemented by educating all pharmacy staff.
      Retrospective audits of turnaround time were conducted at baseline (for all
      orders over a 1-month period) and after implementation of the definitions (for a
      total of 28 days over a 3-month period). Health records and medication orders
      were used to calculate time from prescribing to administration (total turnaround
      time) and time from prescribing to departure from the dispensary (dispensary
      turnaround time). Differences between total and dispensary turnaround times were
      compared with nonparametric statistics. RESULTS: During the baseline audit
      period, 84 (1.1%) of 7787 orders were identified as "stat", "emergent", "urgent",
      or "now". After implementation of the formal definitions, 142 (2.6%) of 5365
      orders were identified by one of these terms. The percentage of orders meeting
      the target dispensary turnaround time of less than 15 min was at least 90% both
      at baseline (76/84 [90%]) and after implementation (129/142 [91%]) (p = 0.80).
      Median dispensary turnaround time for stat and emergent medication orders
      combined (10 versus 9 min, p = 0.27) and for urgent and now medication orders
      combined (10 versus 12 min, p = 0.09) did not change after implementation of
      formal definitions. Similarly, median total turnaround time did not change for
      stat and emergent medication orders combined (30 versus 45 min, p = 0.32), but it
      increased for urgent and now orders combined (35 versus 45 min, p = 0.041).
      CONCLUSIONS: Implementing standardized definitions for "stat", "emergent",
      "urgent", and "now" had no significant effect on dispensary turnaround time.
      However, the majority of orders with these designations met the expected target
      for dispensary turnaround time. Further interventions aimed at other health care
      professionals may be needed to reduce total turnaround time. This research
      supports the concept of interdisciplinary interventions for reducing total
      turnaround time.

PMID- 22479088
TI  - Stability of Ibuprofen solutions in normal saline or 5% dextrose in water.
AB  - BACKGROUND: A shortage of the standard medication for treatment of patent ductus
      arteriosus has necessitated use of parenteral ibuprofen, which is equally
      efficacious for this indication. The beyond-use date recommended by the
      manufacturer is very short and has implications for resource allocation and
      wastage. OBJECTIVE: To evaluate the stability of ibuprofen (undiluted or diluted
      in either 0.9% sodium chloride [normal saline; NS] or 5% dextrose in water [D5W])
      with storage for up to 21 days under refrigeration or at room temperature in
      glass vials or polypropylene syringes. METHODS: Six glass vials, each containing
      undiluted ibuprofen (5 mg/mL), were prepared. In addition, ibuprofen was diluted
      to 2.5 mg/mL in NS or D5W, and 6 syringes were prepared for each diluent (total
      of 12 syringes). Finally, 6 extension tubes were each primed with 1 mL of
      ibuprofen (duplicates of undiluted solution and solutions diluted to 2.5 mg/mL in
      NS or D5W). Half of the vials, syringes, and tubes were stored under
      refrigeration (4 degrees C) and the other half at room temperature (23 degrees
      C). The concentration of ibuprofen was determined by a validated, stability
      indicating liquid chromatographic method on study days 0, 1, 2, 3, 6, 8, 10, 13,
      17, and 21 for samples stored in vials and syringes, or at time 0, 6, 24, and 30
      h for samples stored in tubes. RESULTS: Analysis of variance showed differences
      in the percentage of ibuprofen remaining due to study day (p < 0.001) and diluent
      (p < 0.005), but no differences due to concentration (p = 0.06) or temperature (p
      = 0.12). All solutions of ibuprofen were stable throughout the study period,
      retaining at least 90% of their initial concentration. CONCLUSIONS: Undiluted
      ibuprofen (5 mg/mL) stored in glass vials and ibuprofen diluted to 2.5 mg/mL with
      either NS or D5W and stored in polypropylene syringes will retain more than 92%
      of its initial concentration with storage for up to 14 days at 4 degrees C. A
      beyond-use date of 14 days would allow for up to 24 h storage at 23 degrees C
      during this 14-day period. Storage of ibuprofen solutions in extension tubing
      should not exceed 29 h at 4 degrees C or 17 h at 23 degrees C. Beyond-use dates
      should be applied only after consideration of US Pharmacopeia Revised General
      Chapter <797> guidelines for compounding of sterile preparations.

PMID- 22479089
TI  - Nitrofurantoin-induced pulmonary reaction involving respiratory symptoms: case
      report.

PMID- 22479090
TI  - A Standardized, Structured Approach to Identifying Drug-Related Problems in the
      Intensive Care Unit: FASTHUG-MAIDENS.

PMID- 22479091
TI  - Practice spotlight: pharmacists in a multidisciplinary atrial fibrillation
      clinic.

PMID- 22479092
TI  - Should the pharmacy profession lead the medication reconciliation process?: the
      "pro" side.

PMID- 22479093
TI  - Should the pharmacy profession lead the medication reconciliation process?: the
      "con" side.

PMID- 22479094
TI  - Evaluation of the research grant program of the Foundation of the Canadian
      Society of Hospital Pharmacists, 1995-2008.
AB  - BACKGROUND: Pharmacist-led research has grown substantially over the past 10 to
      15 years. The Research Grant Program of the Research and Education Foundation of
      the Canadian Society of Hospital Pharmacists (CSHP Foundation), initiated in
      1992, is the only funding opportunity available specifically to members of the
      Society. OBJECTIVE: To evaluate the status of research projects funded by the
      Research Grant Program of the CSHP Foundation, to examine the outcomes of these
      projects, and to determine the opinions of grant recipients regarding this
      competition. METHODS: An e-mail survey was sent to each of the 34 hospital
      pharmacist researchers who received funding from the Research Grant Program of
      the CSHP Foundation during the period 1995 to 2008. Survey questions sought to
      evaluate scholarly outcomes (i.e., publications and presentations) from funded
      projects. The opinions of grant recipients about the value of the program were
      also solicited. RESULTS: One of the potential respondents had returned the grant
      money and was ineligible for the survey. Of the 33 potential respondents, 30
      (91%) responded to the survey. Overall, 24 of the projects had been completed at
      the time of the survey, and 19 of these had been published, resulting in a total
      of 26 manuscripts. Abstracts had been presented for 21 of the projects. In total,
      49 abstracts had been presented at national (22), international (13), provincial
      (7) and local (7) conferences. The median award was $5000 (interquartile range
      $5000 to $7500). Eleven of the projects had received additional funding,
      primarily from the recipient's hospital or health authority or from university
      sources. The survey respondents indicated that the grant from the CSHP Foundation
      had been critical to completion of their projects and had been of assistance in
      securing additional funding, when such funding was necessary. Respondents felt
      that dedicated research funding for hospital pharmacists in Canada should
      continue. CONCLUSIONS: The Research Grant Program of the CSHP Foundation has been
      important to hospital pharmacists, enabling a variety of research projects to be
      initiated and completed. The high rate of project completion and the large number
      of publications and presentations resulting from this work speak to both the
      quality of the work and the dedication of the research teams. The CSHP Foundation
      should continue to fund this competition and should explore a more robust model,
      with larger awards and more funded projects each year.

PMID- 22479095
TI  - Developing Preceptors through Virtual Communities and Networks: Experiences from
      a Pilot Project.
AB  - BACKGROUND: Supporting preceptors is critical to the expansion of experiential
      learning opportunities for the pharmacy profession. Informal learning
      opportunities within communities of practitioners are important for hospital
      preceptors. However, such communities may be limited by geographic separation of
      preceptors from peers, faculty members, and supports within the pharmacy services
      department. OBJECTIVE: To use computer-mediated conferencing to create a sense of
      community among preceptors, specifically by using this medium to provide initial
      development of and continuing support for preceptors, and to examine preceptors'
      satisfaction with this approach. METHODS: Thirty-nine preceptors who had
      completed a day-long face-to-face preceptor development workshop and who were
      supervising students in 1 of 2 specific rotation blocks were invited to
      participate in the study. The pharmacists used computer-mediated conferencing to
      meet for virtual networking about specific topics. They met once before the
      student rotation to receive instructions about the technology and to discuss
      student orientation and scheduling, and 3 times during the student rotation for
      open discussion of specific topics. Evaluation and feedback were solicited by
      means of an electronic survey and virtual (i.e., computer-based) feedback
      sessions with an independent facilitator. RESULTS: The response rate was 66%
      (26/39) for the electronic survey, but only 15% (6/39) for the virtual feedback
      sessions. All of the respondents were experienced preceptors, but for 92%
      (22/24), this was their first experience with computer-mediated conferencing.
      Overall, the sessions had a positive reception, and participants found it useful
      to share information and experiences with other preceptors. The main challenges
      were related to the technology, perceived lack of support for their participation
      in the sessions, and inconvenience related to the timing of sessions. CONCLUSION:
      Computer-mediated conferencing allowed preceptors to learn from and to support
      each other despite geographic distance. The participants felt that these sessions
      encouraged them to serve as preceptors regularly. Such encouragement could
      contribute to the retention of preceptors, which is important to the expansion of
      experiential learning.

PMID- 22479096
TI  - Analysis of Orders for QTc-Prolonging Medication for Intensive and Cardiac Care
      Unit Patients with Pre-existing QTc Prolongation (QTIPPP Study).
AB  - BACKGROUND: A prolonged QTc interval on electrocardiography is often used as a
      surrogate marker for ventricular arrhythmia. Medications that can prolong the QTc
      interval may increase the risk of cardiac complications, although the exact
      incidence is unknown. It is reasonable to assume that administration of QTc
      prolonging medications to patients with pre-existing QTc prolongation will
      further increase the risk of cardiac consequences. This study was designed to
      examine the frequency of prescription of QTc-prolonging medications in such
      patients and to explore the potential for clinical pharmacists to minimize the
      associated risks. OBJECTIVES: The primary objective was to identify the number of
      patients with pre-existing prolonged QTc interval for whom QTc-prolonging
      medications were prescribed, from among all patients with orders for QTc
      prolonging medications. The secondary objectives were to determine patterns of
      intervention by clinical pharmacists in these cases and to document any further
      QTc prolongation and occurrence of cardiac events. METHODS: A prospective,
      observational, quality assessment study was conducted over 4.5 months. Adult
      patients admitted to beds with cardiac monitoring by telemetry for whom one or
      more QTc-prolonging medications were ordered were eligible for inclusion.
      Patients were included if the QTc interval was longer than 450 ms on the most
      recent 12-lead electrocardiogram before the QTc-prolonging medication was
      ordered. These patients were followed to identify outcomes of interest after
      administration of QTc-prolonging medication. RESULTS: Overall, a QTc-prolonging
      medication was prescribed for 207 patients. Of these, 53 patients (26%) had pre
      existing prolongation of the QTc interval. Clinical pharmacists made
      recommendations related to 28 medication orders; of these, 16 (57%) were accepted
      by the physician. Fifty-one (96%) of the 53 patients received at least one dose
      of QTc-prolonging medication and were monitored daily for complications. Nine
      (18%) of the 51 patients who underwent daily monitoring experienced at least one
      cardiac event. CONCLUSIONS: A substantial proportion (26%) of patients for whom
      QTc-prolonging medications were prescribed had pre-existing prolongation of the
      QTc interval. Clinical pharmacists may have a role in reducing the risk of
      subsequent complications.

PMID- 22479097
TI  - Survey of graduates of the british columbia pharmacy practice residency programs,
      1973-2009.
AB  - BACKGROUND: The Canadian Hospital Pharmacy Residency Board (CHPRB) first
      introduced accreditation standards to guide the development and maintenance of
      pharmacy residency programs in the 1970s. These standards have evolved over the
      years, including a comprehensive revision in 1998. Ongoing quality assessment of
      residency training is necessary to identify areas for improvement and to ensure
      that residency training keeps pace with continual changes in pharmacists' roles.
      OBJECTIVE: To characterize the practices of graduates of the British Columbia
      Pharmacy Practice Residency Programs (BCPPRPs), to review the effect of residency
      training on their careers, and to assess whether the BCPPRPs achieved their
      educational goals with respect to the 2010 CHPRB accreditation standards.
      METHODS: An 18-question electronic survey was sent by e-mail to all graduates of
      the BCPPRPs from inception in 1973 to 2009. Both quantitative and qualitative
      data were collected, so descriptive, narrative, and formal mixed-methods
      approaches were used for the analysis. RESULTS: Of the estimated 490 graduates,
      144 (29%) completed the survey. About 95% of respondents (125 of 131) agreed that
      the BCPPRPs had adequately prepared them for a career in hospital pharmacy
      practice. A majority strongly or somewhat agreed that their respective programs
      had allowed them to aquire all core competencies. There was less agreement about
      the achievement of project management and leadership skills. Analysis of these
      results by eras (specifically, before and after the 1998 revision of the CHPRB
      accreditation standards) showed statistically significant improvements in
      achievement for 2 of the educational outcomes, "providing evidence-based direct
      patient care as a member of an inter-professional team" (p = 0.001) and "adequate
      training in literature appraisal" (p = 0.005). CONCLUSIONS: A majority of
      respondents recognized that their residency program had a substantial impact on
      their hospital pharmacy careers, especially in terms of developing direct patient
      care skills. The 2010 standards have introduced a specific outcome related to
      leadership skills. These results indicate that both the CHPRB and specific
      residency programs would benefit from discussions clarifying outcomes related to
      project management skills.

PMID- 22479098
TI  - [Not Available].
AB  - BACKGROUND: Drug shortages have been a reality of pharmacy practice for decades.
      However, this problem has become a daily concern for pharmacists in the 21st
      century and extends beyond the pharmaceutical literature. OBJECTIVE: The primary
      objective of this study was to quantify the annual number of drugs in short
      supply and the duration of these shortages. A secondary objective was to describe
      the number of drugs in short supply by manufacturer and therapeutic class.
      METHOD: This descriptive retrospective study examined drug shortages in relation
      to all hospital medication supply contracts in the administrative regions of
      Montreal, Laval, and the Eastern Townships in the province of Quebec. The number
      of inventory shortages, the number of out-of-stock days, and the mean annual
      duration of the shortages were calculated by manufacturer and by therapeutic
      class. The proportions of out-of-stock products and out-of-stock days were also
      calculated by therapeutic class. Descriptive statistical analyses were performed
      (i.e., totals, means, standard deviations, medians, and ranges). RESULTS: There
      were 2400 inventory shortages between January 1, 2006, and August 31, 2010 (56
      month period) for a total of 258 105 out-of-stock days (mean duration +/-
      standard deviation 108 +/- 130 days, range 5 to 1623 days). A total of 70
      manufacturers were implicated in drug shortages over the study period, but 4
      manufacturers were responsible for half (50%) of the shortages and out-of-stock
      days. The shortages affected the majority of therapeutic drug classes on the
      market. However, 3 therapeutic classes (central nervous system drugs, anti
      infective agents, and cardiovascular drugs) accounted for 50% of the shortages.
      CONCLUSION: These are the first Canadian data published on the scope of drug
      shortages in the hospital market. This study has demonstrated that drug shortages
      affect the majority of manufacturers and most therapeutic classes. Further
      studies are required to explore the causes and effects of drug shortages in the
      hospital setting. [Publisher's translation].

PMID- 22479099
TI  - Evaluation of an alcohol withdrawal protocol and a preprinted order set at a
      tertiary care hospital.
AB  - BACKGROUND: Alcohol withdrawal protocols involving symptom-triggered
      administration of benzodiazepine have been established to reduce the duration of
      treatment and the cumulative benzodiazepine dose (relative to usual care).
      However, the effects of a protocol combining fixed-schedule and symptom-triggered
      benzodiazepine dosing are less clear. OBJECTIVE: To assess the efficacy and
      safety of a combination fixed-scheduled and symptom-triggered benzodiazepine
      dosing protocol for alcohol withdrawal, relative to usual care, for medical
      inpatients at a tertiary care hospital. METHODS: A chart review of admissions to
      the internal medicine service for alcohol withdrawal was conducted to compare
      treatment outcomes before (October 2005 to April 2007) and after (October 2007 to
      April 2009) implementation of the combination protocol. The primary outcome was
      duration of benzodiazepine treatment for alcohol withdrawal. The secondary
      outcomes were cumulative benzodiazepine dose administered, safety implications,
      and use of adjunctive medications. RESULTS: A total of 159 patients met the
      inclusion criteria. Assessable data were available for 71 charts from the pre
      implementation period and 72 charts from the post-implementation period. The
      median duration of benzodiazepine treatment was 91 h before implementation and 57
      h after implementation (p < 0.001). Use of the protocol was also associated with
      a significant reduction in severe complications of alcohol withdrawal (50% versus
      33%, p = 0.019), median cumulative benzodiazepine dose (in lorazepam equivalents)
      (20.0 mg versus 15.5 mg, p = 0.026), and use of adjunctive medications (65%
      versus 38%, p = 0.001). The incidence of serious adverse outcomes of treatment
      with benzodiazepines was not significantly different between the 2 groups.
      CONCLUSIONS: Implementation of an alcohol withdrawal protocol with a combination
      of fixed-schedule and symptom-triggered benzodiazepine dosing in a medical ward
      was associated with a shorter duration of benzodiazepine use and a lower
      incidence of severe complications of alcohol withdrawal.

PMID- 22479100
TI  - Development and evaluation of a student pharmacist clinical teaching unit
      utilizing peer-assisted learning.

PMID- 22479101
TI  - Organizational restructuring of regional pharmacy services to enable a new
      pharmacy practice model.

PMID- 22479102
TI  - Practice spotlight: pharmacy practice in a correctional setting.

PMID- 22479103
TI  - Should Pharmacy Informatics Officer Positions be Based in, and Report to, the
      Pharmacy Department, Rather than the Health Information Technology Department?

PMID- 22479104
TI  - Fludrocortisone for heparin-induced hyperkalemia.

PMID- 22479105
TI  - How critical are critical care pharmacists?

PMID- 22479106
TI  - [Not Available].

PMID- 22479107
TI  - Use of methadone for prevention of opioid withdrawal in critically ill children.
AB  - BACKGROUND: Opioids are commonly administered to critically ill children for
      analgesia and sedation, but many patients experience opioid withdrawal upon
      discontinuation. The authors' institution developed a protocol for using
      methadone to prevent opioid withdrawal in children who have received morphine by
      continuous IV infusion for 5 days or longer in the pediatric intensive care unit
      (PICU). OBJECTIVES: The primary objectives were to determine if opioids were
      tapered according to the protocol and to determine the conversion ratio for IV
      morphine to oral methadone that was used. Secondary objectives were to describe
      the methadone dosage used and the clinical outcomes, to evaluate adjustments to
      methadone dosing, and to report the incidence of adverse effects. METHODS: A
      retrospective analysis of charts was conducted for pediatric patients who had
      received morphine by continuous IV infusion for 5 days or longer followed by
      methadone in the PICU between May 2008 and August 2009. Validated scoring systems
      (the Withdrawal Assessment Tool and the State Behavioral Scale) were used to
      assess symptoms of withdrawal and degree of sedation, respectively. RESULTS:
      Forty-three patients were included in the study, with median age of 8 months
      (range 0.25-201 months). For 31 patients (72%), the protocol was not used, and
      there were no patients for whom the protocol was followed to completion. The
      median duration of weaning was 10 days (range 0-91 days). The conversion ratio
      for IV morphine to oral methadone was 1:0.78 for anticipated 5-day weaning and
      1:0.98 for anticipated 10-day weaning. During the first 10 days of weaning, 18
      patients (42%) experienced withdrawal symptoms. The methadone dose was increased
      for 11 (26%) of the 43 patients. Patients were sedated for a median of 1 day
      (range 0-9 days), were comfortable for a median of 6.5 days (range 1-64 days),
      and were agitated for a median of 2.5 days (range 0-23 days). Naloxone was
      required for 2 patients. CONCLUSIONS: The institution's methadone protocol was
      not followed consistently during the study period, and practices for
      transitioning from morphine by continuous IV infusion to methadone with tapering
      were also inconsistent. Further studies are needed to determine the optimal
      conversion ratio for morphine to methadone and the optimal tapering regimen to
      minimize withdrawal symptoms and adverse events.

PMID- 22479108
TI  - Errors Associated with IV Infusions in Critical Care.
AB  - BACKGROUND: All medication errors are serious, but those associated with the IV
      route of administration often result in the most severe outcomes. According to
      the literature, IV medications are associated with 54% of potential adverse
      events, and 56% of medication errors. OBJECTIVES: To determine the type and
      frequency of errors associated with prescribing, documenting, and administering
      IV infusions, and to also determine if a correlation exists between the incidence
      of errors and either the time of day (day versus night) or the day of the week
      (weekday versus weekend) in an academic medicosurgical intensive care unit
      without computerized order entry or documentation. METHODS: As part of a quality
      improvement initiative, a prospective, observational audit was conducted for all
      IV infusions administered to critically ill patients during 40 randomly selected
      shifts over a 7-month period in 2007. For each IV infusion, data were collected
      from 3 sources: direct observation of administration of the medication to the
      patient, the medication administration record, and the patient's medical chart.
      The primary outcome was the occurrence of any infusion-related errors, defined as
      any errors of omission or commission in the context of IV medication therapy that
      harmed or could have harmed the patient. RESULTS: It was determined that up to 21
      separate errors might occur in association with a single dose of an IV
      medication. In total, 1882 IV infusions were evaluated, and 5641 errors were
      identified. Omissions or discrepancies related to documentation accounted for
      92.7% of all errors. The most common errors identified via each of the 3 data
      sources were incomplete labelling of IV tubing (1779 or 31.5% of all errors),
      omission of infusion diluent from the medication administration record (474 or
      8.4% of all errors), and discrepancy between the medication order as recorded in
      the patient's chart and the IV medication that was being infused (105 or 1.9% of
      all errors). CONCLUSIONS: Strict definitions of errors and direct observation
      methods allowed identification of errors at every step of the medication
      administration process that was evaluated. Documentation discrepancies were the
      most prevalent type of errors in this paper-based system.

PMID- 22479109
TI  - Use of parenteral fish oil to reverse cholestasis induced by parenteral nutrition
      in infants with intestinal failure: single-centre case series.

PMID- 22479110
TI  - Prospective audit and feedback of antimicrobial stewardship in critical care:
      program implementation, experience, and challenges.

PMID- 22479111
TI  - [Not Available].

PMID- 22479112
TI  - Practice spotlight: pharmacist practice in an outpatient menopause clinic.

PMID- 22479113
TI  - Should all elderly women receive bisphosphonates to prevent osteoporotic
      fractures?

PMID- 22479115
TI  - Tribute to the reviewers of the canadian journal of hospital pharmacy.

PMID- 22479116
TI  - United we stand.

PMID- 22479117
TI  - [Not Available].

PMID- 22479119
TI  - Ask for what you need, not what you want.

PMID- 22479118
TI  - [Not Available].

PMID- 22479120
TI  - Abstractions, algorithms and data structures for structural bioinformatics in
      PyCogent.
AB  - To facilitate flexible and efficient structural bioinformatics analyses, new
      functionality for three-dimensional structure processing and analysis has been
      introduced into PyCogent - a popular feature-rich framework for sequence-based
      bioinformatics, but one which has lacked equally powerful tools for handling
      stuctural/coordinate-based data. Extensible Python modules have been developed,
      which provide object-oriented abstractions (based on a hierarchical
      representation of macromolecules), efficient data structures (e.g.kD-trees), fast
      implementations of common algorithms (e.g. surface-area calculations), read/write
      support for Protein Data Bank-related file formats and wrappers for external
      command-line applications (e.g. Stride). Integration of this code into PyCogent
      is symbiotic, allowing sequence-based work to benefit from structure-derived data
      and, reciprocally, enabling structural studies to leverage PyCogent's versatile
      tools for phylogenetic and evolutionary analyses.

PMID- 22479121
TI  - A manual low-cost protein-crystallization plate jig for in situ diffraction in
      the home laboratory.
AB  - A prototype jig to attach a protein crystallization plate to a standard X-ray
      goniometer has been designed and constructed in partnership with an engineering
      firm. This allows a low-cost implementation of in situ diffraction using the
      available home-laboratory X-ray source.

PMID- 22479122
TI  - Perspectives on the future of behavior analysis: introductory comments.

PMID- 22479123
TI  - Looking to the future: will behavior analysis survive and prosper?
AB  - Behavior analysis as a discipline currently is doing relatively well. How it will
      do in the future is unclear and depends on how the field, and the world at large,
      changes. Five current characteristics of the discipline that appear to reduce the
      probability that it will survive and prosper are discussed and suggestions for
      improvement are offered. The areas of concern are (a) the small size and limited
      power of the discipline, (b) the growing focus of applied behavior analysis on
      autism spectrum disorders and little else, (c) the esoteric nature of much basic
      research, (d) the proliferation of "applied" research that really isn't applied,
      and (e) the widespread use of imprecise and potentially harmful technical
      language.

PMID- 22479124
TI  - Come on in, the Water is Fine: Achieving Mainstream Relevance through Integration
      with Primary Medical Care.
AB  - Behavior analysis is a generic science, and Skinner's vision for it was that it
      would become a mainstream force, relevant for most if not all human concerns,
      major and minor. Clearly his vision has not been realized. Determining why this
      is the case would require a complex multifactorial analysis. One likely factor is
      that the majority of its basic science findings have been obtained from the study
      of rats and pigeons. Another likely factor, one directly addressed by this paper,
      is that the majority of its applied science findings have been obtained from the
      study of people in only one tail of the normal distribution. Regardless, those
      outside the field see the relevance of behavior analysis to general human affairs
      as very limited. Whether the path behavior analysis is on will lead to widespread
      perception of mainstream relevance anytime soon seems doubtful. An alternative
      route would involve integrating it with a field that has already made the trip
      successfully. A premier example involves primary medical care. This paper argues
      for the integration of behavior analysis with pediatric primary care, sketches a
      method for its accomplishment, and uses diurnal enuresis to illustrate the
      requirements of the method.

PMID- 22479125
TI  - Behavior under the microscope: increasing the resolution of our experimental
      procedures.
AB  - Behavior analysis has exploited conceptual tools whose experimental validity has
      been amply demonstrated, but their relevance to large-scale and fine-grained
      behavioral phenomena remains uncertain, because the experimental analysis of
      these domains faces formidable obstacles of measurement and control. In this
      essay I suggest that, at least at the fine-grained end of the behavioral
      spectrum, we have not taken sufficient advantage of all available procedures.
      Specifically, I propose that an examination of eye movements, joint control, and
      response latency in intraverbal tasks might help us to formulate more complete
      accounts of complex human behavior.

PMID- 22479126
TI  - Behaviorism and the stages of scientific activity.
AB  - Following from an earlier analysis by B. F. Skinner, the present article suggests
      that the verbal processes in science may usefully be viewed as following a three
      stage progression. This progression starts with (a) identification of basic data,
      then moves to (b) description of relations among those data, and ultimately
      concludes with (c) the deployment of higher order concepts in statements about
      organizations of data. The article emphasizes the importance of viewing theory
      and explanation as examples of verbal processes at the later stages, guided by
      the stimulus control from the earlier stages. The article further suggests that
      many theories and explanations in traditional psychology often take a form that
      appears to be from the later stages. However, adequate activity at the earlier
      stages has not preceded those theories and explanations. They therefore do not
      have the benefit of suitable stimulus control from the earlier stages. Rather,
      they reflect some degree of stimulus control by many mentalistic assumptions
      about causal entities and relations. Ultimately, traditional theories and
      explanations influenced by mentalistic assumptions occasion less effective
      interaction with natural events (e.g., through prediction and control) than they
      might otherwise.

PMID- 22479127
TI  - Emergent verbal behavior and analogy: skinnerian and linguistic approaches.
AB  - The production of verbal operants not previously taught is an important aspect of
      language productivity. For Skinner, new mands, tacts, and autoclitics result from
      the recombination of verbal operants. The relation between these mands, tacts,
      and autoclitics is what linguists call analogy, a grammatical pattern that serves
      as a foundation on which a speaker might emit new linguistic forms. Analogy
      appears in linguistics as a regularity principle that characterizes language and
      has been related to how languages change and also to creativity. The approaches
      of neogrammarians like Hermann Paul, as well as those of Jespersen and
      Bloomfield, appear to have influenced Skinner's understanding of verbal
      creativity. Generalization and stimulus equivalence are behavioral processes
      related to the generative grammatical behavior described in the analogy model.
      Linguistic forms and grammatical patterns described in analogy are part of the
      contingencies of reinforcement that produce generalization and stimulus
      equivalence. The analysis of verbal behavior needs linguistic analyses of the
      constituents of linguistic forms and their combination patterns.

PMID- 22479128
TI  - Zen and behavior analysis.
AB  - Zen's challenge for behavior analysis is to explain a repertoire that renders
      analysis itself meaningless-a result following not from scientific or
      philosophical arguments but rather from a unique verbal history generated by
      Zen's methods. Untying Zen's verbal knots suggests how meditation's and koans'
      effects on verbal behavior contribute to Enlightenment and Samadhi. The concept
      of stimulus singularity is introduced to account for why, within Zen's frame of
      reference, its methods can be studied but its primary outcomes (e.g., Samadhi and
      Satori) cannot be described in any conventional sense.

PMID- 22479130
TI  - On distinguishing progressively increasing response requirements for
      reinforcement.
AB  - Several different arrangements have been described for increasing the response
      requirements for reinforcement using the label progressive-ratio schedule. Under
      the original progressive-ratio schedule, the response requirement is increased
      after each reinforcer. Subsequently, arrangements have been used in which the
      number of required responses increases following multiple reinforcers at a single
      response requirement or between sessions. Following an assessment of the
      different types of contingencies that result from such progressive response
      requirements and the labels used to describe them, a set of descriptive labels is
      suggested for these different types of progressively increasing response
      requirements.

PMID- 22479129
TI  - Evaluating the evidence base for relational frame theory: a citation analysis.
AB  - Relational frame theory (RFT) is a contemporary behavior-analytic account of
      language and cognition. Since it was first outlined in 1985, RFT has generated
      considerable controversy and debate, and several claims have been made concerning
      its evidence base. The present study sought to evaluate the evidence base for RFT
      by undertaking a citation analysis and by categorizing all articles that cited
      RFT-related search terms. A total of 174 articles were identified between 1991
      and 2008, 62 (36%) of which were empirical and 112 (64%) were nonempirical
      articles. Further analyses revealed that 42 (68%) of the empirical articles were
      classified as empirical RFT and 20 (32%) as empirical other, whereas 27 (24%) of
      the nonempirical articles were assigned to the nonempirical reviews category and
      85 (76%) to the nonempirical conceptual category. In addition, the present
      findings show that the majority of empirical research on RFT has been conducted
      with typically developing adult populations, on the relational frame of sameness,
      and has tended to be published in either The Psychological Record or the Journal
      of the Experimental Analysis of Behavior. Overall, RFT has made a substantial
      contribution to the literature in a relatively short period of time.

PMID- 22479131
TI  - A critical analysis of conventional descriptions of levels employed in the
      assessment of basic learning abilities.

PMID- 22479132
TI  - The Complete Guide to Autism Treatments: A Parent's Handbook: Make Sure Your
      Child Gets What Works!

PMID- 22479133
TI  - Colony variation in the collective regulation of foraging by harvester ants.
AB  - This study investigates variation in collective behavior in a natural population
      of colonies of the harvester ant, Pogonomyrmex barbatus. Harvester ant colonies
      regulate foraging activity to adjust to current food availability; the rate at
      which inactive foragers leave the nest on the next trip depends on the rate at
      which successful foragers return with food. This study investigates differences
      among colonies in foraging activity and how these differences are associated with
      variation among colonies in the regulation of foraging. Colonies differ in the
      baseline rate at which patrollers leave the nest, without stimulation from
      returning ants. This baseline rate predicts a colony's foraging activity,
      suggesting there is a colony-specific activity level that influences how quickly
      any ant leaves the nest. When a colony's foraging activity is high, the colony is
      more likely to regulate foraging. Moreover, colonies differ in the propensity to
      adjust the rate of outgoing foragers to the rate of forager return. Naturally
      occurring variation in the regulation of foraging may lead to variation in colony
      survival and reproductive success.

PMID- 22479134
TI  - Linking amphibian call structure to the environment: the interplay between
      phenotypic flexibility and individual attributes.
AB  - The structure of the environment surrounding signal emission produces different
      patterns of degradation and attenuation. The expected adjustment of calls to
      ensure signal transmission in an environment was formalized in the acoustic
      adaptation hypothesis. Within this framework, most studies considered anuran
      calls as fixed attributes determined by local adaptations. However, variability
      in vocalizations as a product of phenotypic expression has also been reported.
      Empirical evidence supporting the association between environment and call
      structure has been inconsistent, particularly in anurans. Here, we identify a
      plausible causal structure connecting environment, individual attributes, and
      temporal and spectral adjustments as direct or indirect determinants of the
      observed variation in call attributes of the frog Hypsiboas pulchellus. For that
      purpose, we recorded the calls of 40 males in the field, together with vegetation
      density and other environmental descriptors of the calling site. Path analysis
      revealed a strong effect of habitat structure on the temporal parameters of the
      call, and an effect of site temperature conditioning the size of organisms
      calling at each site and thus indirectly affecting the dominant frequency of the
      call. Experimental habitat modification with a styrofoam enclosure yielded
      results consistent with field observations, highlighting the potential role of
      call flexibility on detected call patterns. Both, experimental and correlative
      results indicate the need to incorporate the so far poorly considered role of
      phenotypic plasticity in the complex connection between environmental structure
      and individual call attributes.

PMID- 22479135
TI  - Resource quality or competition: why increase resource acceptance in the presence
      of conspecifics?
AB  - Some animal species increase resource acceptance rates in the presence of
      conspecifics. Such responses may be adaptive if the presence of conspecifics is a
      reliable indicator of resource quality. Similarly, these responses could
      represent an adaptive reduction in choosiness under high levels of scramble
      competition. Although high resource quality and high levels of scramble
      competition should both favor increased resource acceptance, the contexts in
      which the increase occurs should differ. In this paper, we tested the effect of
      social environment on egg-laying and aggressive behavior in the walnut fly,
      Rhagoletis juglandis, in multiple contexts to determine whether increased
      resource acceptance in the presence of conspecifics was better viewed as a
      response to increased host quality or increased competition. We found that
      grouped females oviposit more readily than isolated females when provided small
      (low-quality) artificial hosts but not when provided large (high-quality)
      artificial hosts, indicating that conspecific presence reduces choosiness.
      Increased resource acceptance was observed even when exposure to conspecifics was
      temporally or spatially separate from exposure to the resource. Finally, we found
      that individuals showed reduced aggression after being housed in groups, as
      expected under high levels of scramble competition. These results indicate that
      the pattern of resource acceptance in the presence of conspecifics may be better
      viewed as a response to increased scramble competition rather than as a response
      to public information about resource quality.

PMID- 22479136
TI  - Progressive parenting behavior in wild golden lion tamarins.
AB  - Young primates in the family Callitrichidae (the marmosets and tamarins) receive
      extensive and relatively prolonged care from adults. Of particular note,
      callitrichid young are routinely provisioned until well after weaning by parents
      and helpers, which is in stark contrast to typical juvenile primates, who must
      acquire most of their food independently once they are weaned. Adults of some
      callitrichid species produce a specialized vocalization that encourages immature
      group members to take proffered food from the caller. Here, I report that wild
      adult golden lion tamarins (Leontopithecus rosalia) not only used this food
      offering call to encourage young, mobile offspring to approach and take captured
      prey from them, but as the young began to spend significant time foraging for
      themselves and to acquire prey by independent means, the frequency of these
      vocalizations in the context of food transfer declined. Adults then began to use
      food-offering calls in a novel context: to direct juveniles to foraging sites
      that contained hidden prey that the adults had found but not captured. During the
      period of these most frequent adult-directed prey captures, the independent prey
      capture success rates of juveniles improved. Thus, adults modified their
      provisioning behavior in a progressive developmentally sensitive manner that may
      have facilitated learning how to find food. I hypothesize that as a result of
      these demonstrations by adults, juveniles either may be encouraged to continue
      foraging despite low return rates or to learn the properties of productive prey
      foraging substrates in a complex environment.

PMID- 22479138
TI  - By any name, female-female competition yields differential mating success.

PMID- 22479137
TI  - Intrasexual competition in females: evidence for sexual selection?
AB  - In spite of recent interest in sexual selection in females, debate exists over
      whether traits that influence female-female competition are sexually selected.
      This review uses female-female aggressive behavior as a model behavioral trait
      for understanding the evolutionary mechanisms promoting intrasexual competition,
      focusing especially on sexual selection. I employ a broad definition of sexual
      selection, whereby traits that influence competition for mates are sexually
      selected, whereas those that directly influence fecundity or offspring survival
      are naturally selected. Drawing examples from across animal taxa, including
      humans, I examine 4 predictions about female intrasexual competition based on the
      abundance of resources, the availability of males, and the direct or indirect
      benefits those males provide. These patterns reveal a key sex difference in
      sexual selection: Although females may compete for the number of mates, they
      appear to compete more so for access to high-quality mates that provide direct
      and indirect (genetic) benefits. As is the case in males, intrasexual selection
      in females also includes competition for essential resources required for access
      to mates. If mate quality affects the magnitude of mating success, then
      restricting sexual selection to competition for quantity of mates may ignore
      important components of fitness in females and underestimate the role of sexual
      selection in shaping female phenotype. In the future, understanding sex
      differences in sexual selection will require further exploration of the extent of
      mutual intrasexual competition and the incorporation of quality of mating success
      into the study of sexual selection in both sexes.

PMID- 22479139
TI  - What is sexual selection and the short herstory of female trait variation.

PMID- 22479140
TI  - Spatial movements and social networks in juvenile male song sparrows.
AB  - The time between fledging and breeding is a critical period in songbird ontogeny,
      but the behavior of young songbirds in the wild is relatively unstudied. The
      types of social relationships juveniles form with other individuals can provide
      insight into the process through which they learn complex behaviors crucial for
      survival, territory establishment, and mate attraction. We used radio telemetry
      to observe social associations of young male song sparrows (Melospiza melodia)
      from May to November. Juvenile song sparrows were frequently observed in social
      flocks and generally associated with more birds in the summer than in the autumn
      months. Most juvenile subjects formed stable social relationships with other
      birds and were seen with the same individual on up to 60% of the days observed.
      The strongest associations occurred with other juvenile males, and these
      individuals were often seen <1 m from the subject, even when the subject moved
      large distances between tracking observations. Associations also had long-term
      behavioral consequences as subjects were more likely to establish territories
      near their associates and learn shared song types. Our results indicate that male
      song sparrows spend a large percentage of the juvenile life stage forming social
      relationships and suggest that these associations may be important for the
      ecology of young birds and the ontogeny of their behaviors.

PMID- 22479141
TI  - Participation of protein Z-dependent protease inhibitor and protein Z system in
      the pathomechanism of thrombotic complications.
AB  - Thrombotic complications of unknown etiology remain a serious diagnostic and
      therapeutic problem. Occurrence of the inherited polymorphisms of genes encoding
      proteins involved in the coagulation cascade is one of the possible causes of
      these complications. In recent years, protein Z (PZ) and PZ-dependent protease
      inhibitor (ZPI) have been added to the list of prothrombotic factors. PZ is a
      glycoprotein serving as a cofactor of ZPI, which is responsible for the
      inhibition of prothrombinase. Expression of the PZ gene is under the control of
      many transcriptional factors; several polymorphisms alternate the rate of gene
      expression. The present article describes the significance of the ZPI-PZ system
      in venous and arterial thrombosis, adverse pregnancy outcomes and
      antiphospholipid syndrome complications.

PMID- 22479142
TI  - The results of in situ saphenous vein bypass for infrainguinal arterial
      reconstruction: Comparison between two types of valvulotomes.
AB  - PURPOSE: To evaluate the authors' experiences with in situ saphenous vein
      bypasses that were performed using two types of valvulotomes and to respectively
      compare their efficacy on the basis of the operative outcomes. METHODS: Between
      June 1993 and December 2008, 103 constructive in situ saphenous vein bypasses
      were performed, of which 53 were performed between 1993 and 2000 using an
      Insitucat valvulotome (B Braun Melsungen AG, Germany), and 50 were performed
      between 2000 and 2008 using a LeMaitre valvulotome (LeMaitre Vascular Inc, USA).
      RESULTS: There were no statistical differences with regard to age, sex and bypass
      procedures between the two groups. Critical limb ischemia (P=0.021) and diabetes
      (P=0.005) were more frequent in the LeMaitre group than the Insitucat group.
      Intraoperative graft revisions (P=0.079) and graft spasms (P=0.638) were less
      frequent in the LeMaitre group. Graft failures in the perioperative period or
      within the first year were less frequent in the LeMaitre group. The five-year
      cumulative primary patency rates were 63.2% and 59.8% in the LeMaitre and
      Insitucat groups, respectively (chi(2)=0.390, not significant). The five-year
      cumulative secondary patency rates were 91.9% and 81.7% in the LeMaitre and
      Insitucat groups, respectively (chi(2)=2.690, not significant). CONCLUSIONS: The
      results suggested that there were no significant differences in the outcome and
      adverse effects between the two types of valvulotomes for in situ saphenous vein
      bypass.

PMID- 22479143
TI  - Edaravone reduces mitochondrial damage due to reperfusion injury following leg
      ischemia in rats.
AB  - PURPOSE: Free radicals have been implicated in reperfusion injury. It was shown
      that the free radical scavenger edaravone might suppress reperfusion injury in
      rat extremities. The present study aimed to elucidate how edaravone suppresses
      reperfusion injury, focusing on its effect on the mitochondrial structure and
      glycogen storage in the lower extremity muscles. METHODS: Sixteen male Lewis rats
      (mean [+/- SD] weight 497+/-32 g) were divided into two groups and injected with
      either 3.0 mg/kg of edaravone (edaravone group, n=8 rats) or the same dose of
      saline (control group, n=8 rats) into the peritoneal cavity. The rat reperfusion
      injury models were created by clamping the bilateral common femoral arteries for
      5 h, then declamping. The muscles were harvested more than 5 h after the start of
      reperfusion. The mitochondrial damage, defined as mitochondrial swelling, was
      examined using a transmission electron microscope at *30,000 original
      magnification (n=3 for each rat). Glycogen storage, defined as a positive
      periodic acid-Schiff stain area, was examined using computerized densitometry
      (n=5 sections for each rat). RESULTS: The mitochondria in the control group
      demonstrated marked swelling (mean mitochondrial size = 0.169+/-0.059 MUm(2)).
      However, the mitochondria in the edaravone group had significantly less swelling
      (mean mitochondrial size = 0.102+/-0.036 MUm(2); P<0.01). The mean percentage of
      positive periodic acid-Schiff stain was also significantly higher in the
      edaravone group than in the control group (51.7+/-6.8% versus 7.3+/-2.1%;
      P<0.01). CONCLUSION: The results suggested that edaravone reduces mitochondrial
      damage due to reperfusion injury, resulting in a high level of glycogen storage.

PMID- 22479144
TI  - Very high central aortic systolic pressures in a young hypertensive patient on
      telmisartan: Is central aortic systolic pressure associated with white coat
      hypertension?
AB  - Central aortic systolic pressure (CASP) is a very well-recognized tool to assess
      the end organ damage in patients with hypertension. It is known that angiotensin
      converting enzyme inhibitors, angiotensin receptor blockers and calcium channel
      blockers reduce CASP more than some antihypertensives such as beta-blockers.
      White coat hypertension with CASP has not been described and validated. The
      present report describes a very anxious 24-year-old patient on telmisartan (an
      angiotensin receptor blocker), with a very high CASP compared with his peripheral
      blood pressure (BP). He had a strong family history of hypertension, and was
      fairly well controlled on 80 mg/day telmisartan, with his BP ranging from 125/80
      mmHg to 130/85 mmHg (home BP monitoring). In May 2009, he underwent routine CASP
      at Tan Tock Seng Hospital (Singapore), and ambulatory BP measurements using a
      BPro watch (HealthSTATS, Singapore). The patient had a CASP of 132 mmHg at the
      hospital, but his calculated CASP by ambulatory BP measurement at 1 pm was 120
      mmHg. His ambulatory BPs were 137/94 mmHg; thus, hydrochlorothiazide was added
      for further control. He was advised to repeat CASP measurements on follow-up in
      six weeks. He followed up on June 18, 2009, and July 30, 2009, and his CASPs were
      139 mmHg and 137 mmHg, respectively. He underwent a magnetic resonance aortogram
      to exclude any obstructive cause for very high CASPs. His magnetic resonance
      aortogram revealed no evidence of coarctation of the aorta. CASP may have
      significant variations due to white coat phenomenon. Further 24 h CASP studies
      are needed to observe whether CASP is subject to white coat phenomenon.

PMID- 22479145
TI  - Successful direct thrombin injection of a femoral artery pseudoaneurysm in an
      anticoagulated patient with a mechanical mitral valve.
AB  - Femoral pseudoaneurysm is a complication of cardiac catheterization and may be
      related to the use of anticoagulants, antiplatelet agents, larger diameter
      sheaths and prolonged duration of sheath insertion. The treatment ranges from
      direct compression with or without direct thrombin injection to surgical repair.
      The present report describes a unique scenario of postcardiac catheterization
      femoral artery pseudoaneursym in a patient with a pre-existing mechanical mitral
      valve requiring anticoagulation. The potential systemic effects of thrombin made
      the patient reluctant to undergo treatment and made thrombin administration a
      challenging proposition. The present report suggests that thrombin injection for
      treating femoral pseudoaneursym in patients with mechanical heart valves on
      chronic anticoagulation can be performed safely.

PMID- 22479146
TI  - Simultaneous Removal of Nitrate and Natural Organic Matter from Drinking Water
      Using a Hybrid Heterotrophic/Autotrophic/Biological Activated Carbon Bioreactor.
AB  - Simultaneous removal of nitrate ([Formula: see text]) and natural organic matter
      (NOM) from drinking water using a hybrid heterotrophic/autotrophic/BAC bioreactor
      (HHABB) was studied in continuous mode. The HHABB consisted of three
      compartments: ethanol heterotrophic part, sulfur autotrophic part, and biological
      activated carbon (BAC)-part (including anoxic and aerobic sections). Experiments
      were performed with [Formula: see text] concentration 30 mg N/L, [Formula: see
      text] loading rate 0.72 kg N/m(3)/d, C : N ratio 0.53, and three concentrations
      of NOM (0.6, 2.6, and 5.7 mg C/L). Overall denitrification rate and efficiency of
      the HHABB were not affected by NOM concentration and were in the suitable ranges
      of 0.69-0.70 kg N/m(3)/d and 96.0%-97.7%, respectively. NOM removal at
      concentration 0.6 mg C/L was not efficient because of organic carbon replacement
      as soluble microbial products. At higher NOM concentrations, total NOM removal
      efficiencies were 55%-65%, 55%-70%, and 55%-65% for dissolved organic carbon,
      trihalomethane formation potential, and UV absorbance at 254 nm (UV(254)),
      respectively. The more efficient compartments of the HHABB for the removal of NOM
      were the ethanol heterotrophic phase and aerobic BAC-phase. The efficiency of the
      HHABB in the removal of NOM was considerable, and the effluent dissolved organic
      carbon and trihalomethane formation potential concentrations were relatively low.
      This study indicated that the HHABB without the anoxic BAC-phase could be a
      feasible alternative for simultaneous removal of [Formula: see text] and NOM from
      drinking water at full scale.

PMID- 22479147
TI  - Decision Tree-Based Classifier Combined with Neural-Based Predictor for Water
      Stage Forecasts in a River Basin During Typhoons: A Case Study in Taiwan.
AB  - To solve the complicated problem of water-stage predictions under the interaction
      of upstream flows and tidal effects during typhoon attacks, this article presents
      a novel approach to river-stage predictions. The proposed CART-ANN model combines
      both the decision trees (classification and regression trees [CART]) and the
      artificial neural network (ANN) techniques, which comprise the multilayer
      perceptron (MLP) and radial basis function (RBFNN). The combined CART-ANN model
      involves a two-step predicting process. First, the CART stage-level classifier
      can classify the river stages into higher, middle, and lower levels. Then, the
      ANN-based water-stage predictors are employed to predict the water stages. The
      proposed model was applied to the Tanshui River Basin in Taiwan. The Taipei
      Bridge, which is close to the estuary and affected by tidal effects, was taken as
      the study gauge. The mean square error and the mean absolute error were used for
      evaluating the variance and bias performances of the models. This study makes two
      contributions. First, the CART-MLP and CART-RBF were modeled to predict river
      stages under tidal effects during typhoons, and they were compared with three
      benchmark models, CART, back-propagation neural network, and RBFNN. Second, the
      CART-RBF successfully demonstrated that it achieved more accurate prediction than
      CART-MLP and three benchmark models.

PMID- 22479148
TI  - NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin
      like functions.
AB  - A unifying feature of eukaryotic nuclear organization is genome segregation into
      transcriptionally active euchromatin and transcriptionally repressed
      heterochromatin. In metazoa, lamin proteins preserve nuclear integrity and higher
      order heterochromatin organization at the nuclear periphery, but no non-metazoan
      lamin orthologues have been identified, despite the likely presence of
      nucleoskeletal elements in many lineages. This suggests a metazoan-specific
      origin for lamins, and therefore that distinct protein elements must compose the
      nucleoskeleton in other lineages. The trypanosomatids are highly divergent
      organisms and possess well-documented but remarkably distinct mechanisms for
      control of gene expression, including polycistronic transcription and trans
      splicing. NUP-1 is a large protein localizing to the nuclear periphery of
      Trypanosoma brucei and a candidate nucleoskeletal component. We sought to
      determine if NUP-1 mediates heterochromatin organization and gene regulation at
      the nuclear periphery by examining the influence of NUP-1 knockdown on
      morphology, chromatin positioning, and transcription. We demonstrate that NUP-1
      is essential and part of a stable network at the inner face of the trypanosome
      nuclear envelope, since knockdown cells have abnormally shaped nuclei with
      compromised structural integrity. NUP-1 knockdown also disrupts organization of
      nuclear pore complexes and chromosomes. Most significantly, we find that NUP-1 is
      required to maintain the silenced state of developmentally regulated genes at the
      nuclear periphery; NUP-1 knockdown results in highly specific mis-regulation of
      telomere-proximal silenced variant surface glycoprotein (VSG) expression sites
      and procyclin loci, indicating a disruption to normal chromatin organization
      essential to life-cycle progression. Further, NUP-1 depletion leads to increased
      VSG switching and therefore appears to have a role in control of antigenic
      variation. Thus, analogous to vertebrate lamins, NUP-1 is a major component of
      the nucleoskeleton with key roles in organization of the nuclear periphery,
      heterochromatin, and epigenetic control of developmentally regulated loci.

PMID- 22479149
TI  - Mediator acts upstream of the transcriptional activator Gal4.
AB  - The proteasome inhibitor MG132 had been shown to prevent galactose induction of
      the S. cerevisiae GAL1 gene, demonstrating that ubiquitin proteasome-dependent
      degradation of transcription factors plays an important role in the regulation of
      gene expression. The deletion of the gene encoding the F-box protein Mdm30 had
      been reported to stabilize the transcriptional activator Gal4 under inducing
      conditions and to lead to defects in galactose utilization, suggesting that
      recycling of Gal4 is required for its function. Subsequently, however, it was
      argued that Gal4 remains stably bound to the enhancer under inducing conditions,
      suggesting that proteolytic turnover of Gal4 might not be required for its
      function. We have performed an alanine-scanning mutagenesis of ubiquitin and
      isolated a galactose utilization-defective ubiquitin mutant. We have used it for
      an unbiased suppressor screen and identified the inhibitor Gal80 as a suppressor
      of the transcriptional defects of the ubiquitin mutant, indicating that the
      protein degradation of the inhibitor Gal80, and not of the activator Gal4, is
      required for galactose induction of the GAL genes. We also show that in the
      absence of Gal80, Mdm30 is not required for Gal4 function, strongly supporting
      this hypothesis. Furthermore, we have found that Mediator controls the galactose
      induced protein degradation of Gal80, which places Mediator genetically upstream
      of the activator Gal4. Mediator had originally been isolated by its ability to
      respond to transcriptional activators, and here we have discovered a leading role
      for Mediator in the process of transcription. The protein kinase Snf1 senses the
      inducing conditions and transduces the signal to Mediator, which initiates the
      degradation of the inhibitor Gal80 with the help of the E3 ubiquitin ligase
      SCF(Mdm30). The ability of Mediator to control the protein degradation of
      transcriptional inhibitors indicates that Mediator is actually able to direct its
      own recruitment to gene promoters.

PMID- 22479150
TI  - Research chimpanzees may get a break.
AB  - A recent report by the Institute of Medicine leaves few urgent reasons standing
      for the continued use of chimpanzees in biomedical research. It is high time to
      think about their retirement, Frans de Waal argues, without neglecting prospects
      for non-invasive research on behavior, cognition, and genetics.

PMID- 22479151
TI  - Global gradients in vertebrate diversity predicted by historical area
      productivity dynamics and contemporary environment.
AB  - Broad-scale geographic gradients in species richness have now been extensively
      documented, but their historical underpinning is still not well understood. While
      the importance of productivity, temperature, and a scale dependence of the
      determinants of diversity is broadly acknowledged, we argue here that limitation
      to a single analysis scale and data pseudo-replication have impeded an integrated
      evolutionary and ecological understanding of diversity gradients. We develop and
      apply a hierarchical analysis framework for global diversity gradients that
      incorporates an explicit accounting of past environmental variation and provides
      an appropriate measurement of richness. Due to environmental niche conservatism,
      organisms generally reside in climatically defined bioregions, or "evolutionary
      arenas," characterized by in situ speciation and extinction. These bioregions
      differ in age and their total productivity and have varied over time in area and
      energy available for diversification. We show that, consistently across the four
      major terrestrial vertebrate groups, current-day species richness of the world's
      main 32 bioregions is best explained by a model that integrates area and
      productivity over geological time together with temperature. Adding finer scale
      variation in energy availability as an ecological predictor of within-bioregional
      patterns of richness explains much of the remaining global variation in richness
      at the 110 km grain. These results highlight the separate evolutionary and
      ecological effects of energy availability and provide a first conceptual and
      empirical integration of the key drivers of broad-scale richness gradients.
      Avoiding the pseudo-replication that hampers the evolutionary interpretation of
      non-hierarchical macroecological analyses, our findings integrate evolutionary
      and ecological mechanisms at their most relevant scales and offer a new synthesis
      regarding global diversity gradients.

PMID- 22479153
TI  - Historical and contemporary factors govern global biodiversity patterns.
AB  - A novel hierarchical framework integrates the effects of time, area,
      productivity, and temperature at their respective relevant scales and
      successfully predicts the latitudinal gradient in global vertebrate diversity.

PMID- 22479152
TI  - Reasoning, learning, and creativity: frontal lobe function and human decision
      making.
AB  - The frontal lobes subserve decision-making and executive control--that is, the
      selection and coordination of goal-directed behaviors. Current models of frontal
      executive function, however, do not explain human decision-making in everyday
      environments featuring uncertain, changing, and especially open-ended situations.
      Here, we propose a computational model of human executive function that clarifies
      this issue. Using behavioral experiments, we show that unlike others, the
      proposed model predicts human decisions and their variations across individuals
      in naturalistic situations. The model reveals that for driving action, the human
      frontal function monitors up to three/four concurrent behavioral strategies and
      infers online their ability to predict action outcomes: whenever one appears more
      reliable than unreliable, this strategy is chosen to guide the selection and
      learning of actions that maximize rewards. Otherwise, a new behavioral strategy
      is tentatively formed, partly from those stored in long-term memory, then probed,
      and if competitive confirmed to subsequently drive action. Thus, the human
      executive function has a monitoring capacity limited to three or four behavioral
      strategies. This limitation is compensated by the binary structure of executive
      control that in ambiguous and unknown situations promotes the exploration and
      creation of new behavioral strategies. The results support a model of human
      frontal function that integrates reasoning, learning, and creative abilities in
      the service of decision-making and adaptive behavior.

PMID- 22479154
TI  - Improving ethical review of research involving incentives for health promotion.
AB  - Alex London and colleagues propose new ethical frameworks for evaluating the
      risks associated with research in which financial or other incentives are used to
      promote healthy behavior.

PMID- 22479155
TI  - Intermittent preventive treatment for malaria in Papua New Guinean infants
      exposed to Plasmodium falciparum and P. vivax: a randomized controlled trial.
AB  - BACKGROUND: Intermittent preventive treatment in infants (IPTi) has been shown in
      randomized trials to reduce malaria-related morbidity in African infants living
      in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear
      whether IPTi is an appropriate prevention strategy in non-African settings or
      those co-endemic for P. vivax (Pv). METHODS AND FINDINGS: In this study, 1,121
      Papua New Guinean infants were enrolled into a three-arm placebo-controlled
      randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and
      1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate
      (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo.
      Both participants and study teams were blinded to treatment allocation. The
      primary end point was protective efficacy (PE) against all episodes of clinical
      malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The
      PE (compared to placebo) against clinical malaria episodes (caused by all
      species) was 29% (95% CI, 10-43, p <= 0.001) in children receiving SP-AQ and 12%
      (95% CI, -11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher
      against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9-54, p =
      0.012) and Pv incidence was 23% (95% CI, 0-41, p = 0.048) lower than in the
      placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95%
      CI, 4-51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, -24 to 26, p =
      0.759). Number of observed adverse events/serious adverse events did not differ
      between treatment arms (p > 0.55). None of the serious adverse events were
      thought to be treatment-related, and the vomiting rate was low in both treatment
      groups (1.4%-2.0%). No rebound in malaria morbidity was observed for 6 mo
      following the intervention. CONCLUSIONS: IPTi using a long half-life drug
      combination is efficacious for the prevention of malaria and anemia in infants
      living in a region highly endemic for both Pf and Pv.

PMID- 22479157
TI  - New research on childbirth has the potential to empower women's decision making,
      but more is needed.
AB  - The PLoS Medicine editors discuss new research studies on the risks associated
      with mode of childbirth following caesarean section.

PMID- 22479156
TI  - No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV
      infection: the randomized Primo-SHM trial.
AB  - BACKGROUND: The objective of this study was to assess the benefit of temporary
      combination antiretroviral therapy (cART) during primary HIV infection (PHI).
      METHODS AND FINDINGS: Adult patients with laboratory evidence of PHI were
      recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to
      receive no treatment or 24 or 60 wk of cART (allocation in a 1?1?1 ratio); if
      therapy was clinically indicated, participants were randomized over the two
      treatment arms (allocation in a 1?1 ratio). Primary end points were (1) viral set
      point, defined as the plasma viral load 36 wk after randomization in the no
      treatment arm and 36 wk after treatment interruption in the treatment arms, and
      (2) the total time that patients were off therapy, defined as the time between
      randomization and start of cART in the no treatment arm, and the time between
      treatment interruption and restart of cART in the treatment arms. cART was
      (re)started in case of confirmed CD4 cell count < 350 cells/mm(3) or symptomatic
      HIV disease. In total, 173 participants were randomized. The modified intention
      to-treat analysis comprised 168 patients: 115 were randomized over the three
      study arms, and 53 randomized over the two treatment arms. Of the 115 patients
      randomized over the three study arms, mean viral set point was 4.8 (standard
      deviation 0.6) log(10) copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3
      (0.9) log(10) copies/ml in the 24- and 60-wk treatment arms (between groups: p <
      0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI
      0.0-1.8) y compared to 3.0 (1.9-4.2) and 1.8 (0.5-3.0) y in the 24- and 60-wk
      treatment arms (log rank test, p < 0.001). In the adjusted Cox analysis, both 24
      wk (hazard ratio 0.42 [95% CI 0.25-0.73]) and 60 wk of early treatment (hazard
      ratio 0.55 [0.32-0.95]) were associated with time to (re)start of cART.
      CONCLUSIONS: In this trial, temporary cART during PHI was found to transiently
      lower the viral set point and defer the restart of cART during chronic HIV
      infection.

PMID- 22479158
TI  - Is Meperidine the Drug That Just Won't Die?

PMID- 22479159
TI  - Neonatal pharmacology: extensive interindividual variability despite limited
      size.
AB  - Providing safe and effective drug therapy to neonates requires knowledge of the
      impact of development on the pharmacokinetics and pharmacodynamics of drugs.
      Although maturational changes are observed throughout childhood, they are most
      prominent during the first year of life. Several of these processes overlap,
      making development an extremely dynamic system in the newborn compared with that
      in infants, children, or adults. Changes in body composition and porportions,
      liver mass, metabolic activity, and renal function collectively affect the
      pharmacokinetic behavior of medications. Instead of simply adapting doses by
      scaling adult or pediatric doses on the basis of a patient's weight and/or body
      surface area, integrated knowledge of clinical maturation and developmental
      pharmacology is critical to the safe and effective use of medications in
      neonates. Unfortunately, the effects of human ontogeny on both pharmacokinetics
      and pharmacodynamics have not been well established in these early stages of
      life, and information regarding the influence of developmental changes on the
      pharmacodynamics of medications is even more limited. Theoretically, age
      dependent variations in receptor number and affinity for drugs have significant
      potential to influence an individual's response to drug therapy. In this review,
      some of the relevant covariates of pharmacokinetics and pharmacodynamics in
      neonates are reviewed and illustrated based on the published literature.

PMID- 22479160
TI  - Meperidine restriction in a pediatric hospital.
AB  - BACKGROUND: Much has been published revealing concerns surrounding the use of
      meperidine due to associated toxicities, drug interactions, and lack of proven
      efficacy. Thus, many adult institutions have chosen to remove or limit the use of
      this agent, while little has been published about the restriction of meperidine
      in pediatrics. Many clinicians feel there are still clinical situations in which
      this agent may be useful. OBJECTIVE: To describe methods taken in a pediatric
      hospital to restrict the use of meperidine and review literature describing uses
      of meperidine as a second-line agent. METHODS: In our pediatric institution, a
      policy to restrict the use of meperidine was developed, approved, and
      implemented. An assessment of meperidine's use 6 months prior to policy
      implementation was done, along with a postinitiation review of use. RESULTS: Data
      revealed that the use of meperidine dropped from 646 doses in 84 patients to 226
      doses in 27 patients after restriction, as anticipated. Previous to
      implementation of these restrictions, orthopedics physicians ordered the majority
      of meperidine prescriptions, while the gastroenterology service ordered the
      majority of meperidine prescriptions after implementation of the restriction
      policy. However, the use of the required form was not widely adopted, with only
      30% of practitioners utilizing it postrestriction. Widespread restriction of
      meperidine and education about use of the form at this institution are still
      under way. CONCLUSION: Not only are there limited reasons for using meperidine,
      there are acceptable alternatives for every known indication. Limiting
      meperidine's use via a restriction policy and/or removal from the institution
      formulary can help limit the use of this potentially toxic agent in the pediatric
      patient.

PMID- 22479161
TI  - Comparison of levalbuterol and racemic albuterol based on cardiac adverse effects
      in children.
AB  - OBJECTIVE: To compare the cardiac effects of levalbuterol with those of racemic
      albuterol based on changes in heart rate (HR) in pediatric patients. METHODS: The
      medical records of hospitalized children ages 1 month to 12 years, who received
      either levalbuterol or racemic albuterol via nebulizer for 3 consecutive doses
      between January 2006 and December 2008 were reviewed. The documented HR was
      collected prior to and after each administered dose of bronchodilator. The
      primary outcome was the largest percentage of change in HR between groups.
      Secondary outcomes of comparisons of the number of patients who had more than a
      10% change in HR and incidence of tachycardia were included. RESULTS: A total of
      50 patients, 25 in each group, was included in the study. All patients in the
      racemic albuterol group received 2.5 mg per dose, while most of the patients in
      the levalbuterol group received 0.63 mg per dose (19 patients, 76%). Only 6
      levalbuterol patients received a dose of 1.25 mg. Nineteen of 25 patients (76%)
      in the levalbuterol group were tachycardic prior to the first recorded dose
      compared to 15 patients (60%) in the racemic albuterol group (p = 0.36). The
      median of the largest percentage of change in HR was 4.1% (interquartile range
      [IQR], 1.8-8.7) in the levalbuterol group compared to 5% (IQR, 1.9-7.8) in the
      racemic albuterol group (p = 0.763). Four patients in the levalbuterol group
      experienced an HR increase of more than 10% compared to 5 patients in the racemic
      albuterol group (p = 1.0). CONCLUSION: Levalbuterol and racemic albuterol
      bronchodilator therapies produced similar effects on HR. No clinically
      significant differences were detected in HR changes between the two treatment
      groups, despite administration of a larger equipotent albuterol dose in the
      racemic albuterol group than in the levalbuterol group.

PMID- 22479162
TI  - Prophylactic ketoconazole shampoo for tinea capitis in a high-risk pediatric
      population.
AB  - OBJECTIVES: Although topical agents for the treatment of tinea capitis decrease
      viable fungal elements and reduce shedding, their use as a prophylactic agent has
      not been investigated. This study evaluated the effectiveness of a prophylactic
      ketoconazole shampoo (Nizoral 2%) protocol to reduce the number of clinically
      evident tinea capitis infections in a high-risk African American, urban
      population. METHODS: We conducted a retrospective analysis of a ketoconazole
      prophylaxis protocol that was implemented at an urban pediatric clinic for
      medically fragile children. Patients at high risk for tinea capitis received
      twice-weekly ketoconazole shampoo. The primary outcome of the study was a
      reduction in the number of documented tinea capitis infections between the 12
      month preprotocol and 12-month postprotocol periods. A secondary outcome included
      the evaluation of predisposing risk factors for acquiring tinea infections.
      RESULTS: Ninety-seven patients, with a mean age of 8.06 years, were included.
      Most patients (78%) were African American. There were a total of 13 tinea capitis
      infections during the 12-month preprotocol period. During the 12-month
      postprotocol period, 41 infections were documented: 37 (90.2%) in the prophylaxis
      group and 4 (9.8%) in the nonprophylaxis group. The average numbers of per
      patient infections in the postprotocol period were 0.79 and 0.08 in the
      prophylaxis and nonprophylaxis groups, respectively. Initiation of prophylaxis
      did not reduce tinea capitis infections (p=NS). Previous history of infection and
      a high level of care were significant predictors of infections (p<0.05).
      CONCLUSIONS: Improved hygiene, adherence to prescribed treatment regimens, and
      prevention of recurrent environmental exposure to surviving fomites should be
      stressed in high-risk patients and supersede the need for an antifungal
      (ketoconazole shampoo) prophylaxis protocol.

PMID- 22479163
TI  - Using a Trigger Tool to Assess Adverse Drug Events in a Children's Rehabilitation
      Hospital.
AB  - INTRODUCTION: Some of the most common actions after an adverse drug event (ADE)
      have been carefully listed, studied, and described as "triggers." Trigger-based
      tools for finding and evaluating ADEs have been validated in varied patient
      populations. A recent article described the frequency and severity of ADEs in
      hospitalized children in tertiary care children's hospitals. Our objective was to
      discover whether children in a pediatric rehabilitation setting are at higher
      risk for ADEs because of polypharmacy, or at a lower risk because of relative
      overall clinical stability. METHODS: A pediatric inpatient trigger tool was used
      in 3 groups of children hospitalized in a pediatric rehabilitation setting. ADE
      frequencies and patient characteristics were compared with values from a
      multicenter study using the same tools in pediatric tertiary care hospitals.
      Changes in ADE frequency over time were assessed (2005, n=20; 2006, n=20; 2008,
      n=19). RESULTS: No serious ADEs were newly discovered using the trigger tool.
      Nearly all of the ADEs (16 of 17) discovered by the trigger tool had not been
      voluntarily reported to the hospital's event reporting program. ADE frequencies
      expressed per patient were higher than those seen in tertiary care children's
      hospitals. Longer lengths of stay resulted in lower ADE frequencies when
      expressed per day. ADE frequency increased in the institution over time,
      reflecting increases in the acuity and complexity of patients cared for at this
      facility. Many ADEs affected bowel frequency. CONCLUSIONS: Systematic chart
      review using a trigger tool discovered ADEs that had not been voluntarily
      reported or evaluated. ADEs in pediatric rehabilitation patients occurred less
      often than those in tertiary pediatric care when expressed as rates per day, but
      were more frequent when expressed per patient or per medication. Types and
      severity of ADEs in pediatric rehabilitation can guide monitoring and attention
      to specific areas of care.

PMID- 22479164
TI  - Assessment of web-based training modules on learning facilitation for advanced
      pharmacy practice experiences in pediatrics.
AB  - OBJECTIVES: To assess the effectiveness of web-based training (WBT) modules to
      enhance and facilitate student pharmacists' learning and their ability to provide
      pharmaceutical care to children during a pediatric advanced pharmacy practice
      experience (APPE). METHODS: Pediatric-specific WBT modules were developed for
      completion by APPE students during a 4-week rotation. Pediatric modules covered
      developmental pharmacology; antimicrobial use and monitoring; fluids,
      electrolytes, and dehydration; and drug information. Students were responsible
      for completing all modules within the first week of the APPE. Preassessments and
      postassessments consisted of 8 to 10 multiple-choice questions, with scores
      ranging from 0 to 100 points. Data were analyzed using descriptive statistics and
      paired t tests. RESULTS: Statistically significant improvements in postassessment
      scores were achieved for 3 of the 4 modules. Significant improvements were not
      observed in the antimicrobial use and monitoring module. Most student pharmacists
      either somewhat or strongly agreed that the modules improved their understanding
      of pharmaceutical care for children. CONCLUSIONS: WBT modules, taken during an
      APPE rotation, may expand and improve student pharmacists' understanding of
      pharmaceutical care in pediatric patients.

PMID- 22479165
TI  - Rhabdomyolysis following a short course of clarythromycin.
AB  - A healthy 5-year-old girl developed myalgia and an elevated creatine kinase
      concentration after 4 days of normal doses of clarithromycin. Myalgias resolved
      and creatine kinase values returned to normal following discontinuation of
      clarithromycin. No other precipitating factors or interacting drugs were
      identified; hence, clarithromycin was suspected as the cause of the
      rhabdomyolysis.

PMID- 22479167
TI  - Pediatric news.

PMID- 22479166
TI  - Worsening bradycardia following antithymocyte globulin treatment of severe
      aplastic anemia.
AB  - Immunosuppressive regimens, which include antithymocyte globulin (ATG), are
      widely used for the treatment of severe aplastic anemia (SAA). However,
      bradycardia has been reported only as a rare side effect of ATG therapy in the
      manufacturer's product information and, in rare cases, in the adult literature.
      We present an adolescent with SAA and preexisting bradycardia who underwent
      immunosuppression therapy with ATG, methylprednisolone, and tacrolimus and
      developed profound sinus bradycardia with successive doses of ATG.

PMID- 22479168
TI  - Neural network mechanisms underlying stimulus driven variability reduction.
AB  - It is well established that the variability of the neural activity across trials,
      as measured by the Fano factor, is elevated. This fact poses limits on
      information encoding by the neural activity. However, a series of recent
      neurophysiological experiments have changed this traditional view. Single cell
      recordings across a variety of species, brain areas, brain states and stimulus
      conditions demonstrate a remarkable reduction of the neural variability when an
      external stimulation is applied and when attention is allocated towards a
      stimulus within a neuron's receptive field, suggesting an enhancement of
      information encoding. Using an heterogeneously connected neural network model
      whose dynamics exhibits multiple attractors, we demonstrate here how this
      variability reduction can arise from a network effect. In the spontaneous state,
      we show that the high degree of neural variability is mainly due to fluctuation
      driven excursions from attractor to attractor. This occurs when, in the parameter
      space, the network working point is around the bifurcation allowing multistable
      attractors. The application of an external excitatory drive by stimulation or
      attention stabilizes one specific attractor, eliminating in this way the
      transitions between the different attractors and resulting in a net decrease in
      neural variability over trials. Importantly, non-responsive neurons also exhibit
      a reduction of variability. Finally, this reduced variability is found to arise
      from an increased regularity of the neural spike trains. In conclusion, these
      results suggest that the variability reduction under stimulation and attention is
      a property of neural circuits.

PMID- 22479169
TI  - Thermodynamic state ensemble models of cis-regulation.
AB  - A major goal in computational biology is to develop models that accurately
      predict a gene's expression from its surrounding regulatory DNA. Here we present
      one class of such models, thermodynamic state ensemble models. We describe the
      biochemical derivation of the thermodynamic framework in simple terms, and lay
      out the mathematical components that comprise each model. These components
      include (1) the possible states of a promoter, where a state is defined as a
      particular arrangement of transcription factors bound to a DNA promoter, (2) the
      binding constants that describe the affinity of the protein-protein and protein
      DNA interactions that occur in each state, and (3) whether each state is capable
      of transcribing. Using these components, we demonstrate how to compute a cis
      regulatory function that encodes the probability of a promoter being active. Our
      intention is to provide enough detail so that readers with little background in
      thermodynamics can compose their own cis-regulatory functions. To facilitate this
      goal, we also describe a matrix form of the model that can be easily coded in any
      programming language. This formalism has great flexibility, which we show by
      illustrating how phenomena such as competition between transcription factors and
      cooperativity are readily incorporated into these models. Using this framework,
      we also demonstrate that Michaelis-like functions, another class of cis
      regulatory models, are a subset of the thermodynamic framework with specific
      assumptions. By recasting Michaelis-like functions as thermodynamic functions, we
      emphasize the relationship between these models and delineate the specific
      circumstances representable by each approach. Application of thermodynamic state
      ensemble models is likely to be an important tool in unraveling the physical
      basis of combinatorial cis-regulation and in generating formalisms that
      accurately predict gene expression from DNA sequence.

PMID- 22479171
TI  - Ten simple rules for starting a company.

PMID- 22479170
TI  - Collective dynamics differentiates functional divergence in protein evolution.
AB  - Protein evolution is most commonly studied by analyzing related protein sequences
      and generating ancestral sequences through Bayesian and Maximum Likelihood
      methods, and/or by resurrecting ancestral proteins in the lab and performing
      ligand binding studies to determine function. Structural and dynamic evolution
      have largely been left out of molecular evolution studies. Here we incorporate
      both structure and dynamics to elucidate the molecular principles behind the
      divergence in the evolutionary path of the steroid receptor proteins. We
      determine the likely structure of three evolutionarily diverged ancestral steroid
      receptor proteins using the Zipping and Assembly Method with FRODA (ZAMF). Our
      predictions are within ~2.7 A all-atom RMSD of the respective crystal structures
      of the ancestral steroid receptors. Beyond static structure prediction, a
      particular feature of ZAMF is that it generates protein dynamics information. We
      investigate the differences in conformational dynamics of diverged proteins by
      obtaining the most collective motion through essential dynamics. Strikingly, our
      analysis shows that evolutionarily diverged proteins of the same family do not
      share the same dynamic subspace, while those sharing the same function are
      simultaneously clustered together and distant from those, that have functionally
      diverged. Dynamic analysis also enables those mutations that most affect dynamics
      to be identified. It correctly predicts all mutations (functional and permissive)
      necessary to evolve new function and ~60% of permissive mutations necessary to
      recover ancestral function.

PMID- 22479172
TI  - Decoding unattended fearful faces with whole-brain correlations: an approach to
      identify condition-dependent large-scale functional connectivity.
AB  - Processing of unattended threat-related stimuli, such as fearful faces, has been
      previously examined using group functional magnetic resonance (fMRI) approaches.
      However, the identification of features of brain activity containing sufficient
      information to decode, or "brain-read", unattended (implicit) fear perception
      remains an active research goal. Here we test the hypothesis that patterns of
      large-scale functional connectivity (FC) decode the emotional expression of
      implicitly perceived faces within single individuals using training data from
      separate subjects. fMRI and a blocked design were used to acquire BOLD signals
      during implicit (task-unrelated) presentation of fearful and neutral faces. A
      pattern classifier (linear kernel Support Vector Machine, or SVM) with linear
      filter feature selection used pair-wise FC as features to predict the emotional
      expression of implicitly presented faces. We plotted classification accuracy vs.
      number of top N selected features and observed that significantly higher than
      chance accuracies (between 90-100%) were achieved with 15-40 features. During
      fearful face presentation, the most informative and positively modulated FC was
      between angular gyrus and hippocampus, while the greatest overall contributing
      region was the thalamus, with positively modulated connections to bilateral
      middle temporal gyrus and insula. Other FCs that predicted fear included superior
      occipital and parietal regions, cerebellum and prefrontal cortex. By comparison,
      patterns of spatial activity (as opposed to interactivity) were relatively
      uninformative in decoding implicit fear. These findings indicate that whole-brain
      patterns of interactivity are a sensitive and informative signature of unattended
      fearful emotion processing. At the same time, we demonstrate and propose a
      sensitive and exploratory approach for the identification of large-scale,
      condition-dependent FC. In contrast to model-based, group approaches, the current
      approach does not discount the multivariate, joint responses of multiple
      functional connections and is not hampered by signal loss and the need for
      multiple comparisons correction.

PMID- 22479173
TI  - "Guilt by association" is the exception rather than the rule in gene networks.
AB  - Gene networks are commonly interpreted as encoding functional information in
      their connections. An extensively validated principle called guilt by association
      states that genes which are associated or interacting are more likely to share
      function. Guilt by association provides the central top-down principle for
      analyzing gene networks in functional terms or assessing their quality in
      encoding functional information. In this work, we show that functional
      information within gene networks is typically concentrated in only a very few
      interactions whose properties cannot be reliably related to the rest of the
      network. In effect, the apparent encoding of function within networks has been
      largely driven by outliers whose behaviour cannot even be generalized to
      individual genes, let alone to the network at large. While experimentalist-driven
      analysis of interactions may use prior expert knowledge to focus on the small
      fraction of critically important data, large-scale computational analyses have
      typically assumed that high-performance cross-validation in a network is due to a
      generalizable encoding of function. Because we find that gene function is not
      systemically encoded in networks, but dependent on specific and critical
      interactions, we conclude it is necessary to focus on the details of how networks
      encode function and what information computational analyses use to extract
      functional meaning. We explore a number of consequences of this and find that
      network structure itself provides clues as to which connections are critical and
      that systemic properties, such as scale-free-like behaviour, do not map onto the
      functional connectivity within networks.

PMID- 22479174
TI  - Topic pages: PLoS Computational Biology meets Wikipedia.

PMID- 22479175
TI  - The rate of beneficial mutations surfing on the wave of a range expansion.
AB  - Many theoretical and experimental studies suggest that range expansions can have
      severe consequences for the gene pool of the expanding population. Due to
      strongly enhanced genetic drift at the advancing frontier, neutral and weakly
      deleterious mutations can reach large frequencies in the newly colonized regions,
      as if they were surfing the front of the range expansion. These findings raise
      the question of how frequently beneficial mutations successfully surf at shifting
      range margins, thereby promoting adaptation towards a range-expansion phenotype.
      Here, we use individual-based simulations to study the surfing statistics of
      recurrent beneficial mutations on wave-like range expansions in linear habitats.
      We show that the rate of surfing depends on two strongly antagonistic factors,
      the probability of surfing given the spatial location of a novel mutation and the
      rate of occurrence of mutations at that location. The surfing probability
      strongly increases towards the tip of the wave. Novel mutations are unlikely to
      surf unless they enjoy a spatial head start compared to the bulk of the
      population. The needed head start is shown to be proportional to the inverse
      fitness of the mutant type, and only weakly dependent on the carrying capacity.
      The precise location dependence of surfing probabilities is derived from the non
      extinction probability of a branching process within a moving field of growth
      rates. The second factor is the mutation occurrence which strongly decreases
      towards the tip of the wave. Thus, most successful mutations arise at an
      intermediate position in the front of the wave. We present an analytic theory for
      the tradeoff between these factors that allows to predict how frequently
      substitutions by beneficial mutations occur at invasion fronts. We find that
      small amounts of genetic drift increase the fixation rate of beneficial mutations
      at the advancing front, and thus could be important for adaptation during species
      invasions.

PMID- 22479176
TI  - Dynamical modeling of collective behavior from pigeon flight data: flock cohesion
      and dispersion.
AB  - Several models of flocking have been promoted based on simulations with
      qualitatively naturalistic behavior. In this paper we provide the first direct
      application of computational modeling methods to infer flocking behavior from
      experimental field data. We show that this approach is able to infer general
      rules for interaction, or lack of interaction, among members of a flock or, more
      generally, any community. Using experimental field measurements of homing pigeons
      in flight we demonstrate the existence of a basic distance dependent
      attraction/repulsion relationship and show that this rule is sufficient to
      explain collective behavior observed in nature. Positional data of individuals
      over time are used as input data to a computational algorithm capable of building
      complex nonlinear functions that can represent the system behavior. Topological
      nearest neighbor interactions are considered to characterize the components
      within this model. The efficacy of this method is demonstrated with simulated
      noisy data generated from the classical (two dimensional) Vicsek model. When
      applied to experimental data from homing pigeon flights we show that the more
      complex three dimensional models are capable of simulating trajectories, as well
      as exhibiting realistic collective dynamics. The simulations of the reconstructed
      models are used to extract properties of the collective behavior in pigeons, and
      how it is affected by changing the initial conditions of the system. Our results
      demonstrate that this approach may be applied to construct models capable of
      simulating trajectories and collective dynamics using experimental field
      measurements of herd movement. From these models, the behavior of the individual
      agents (animals) may be inferred.

PMID- 22479177
TI  - A foot in the door for dermatophyte research.

PMID- 22479178
TI  - In situ microscopy analysis reveals local innate immune response developed around
      Brucella infected cells in resistant and susceptible mice.
AB  - Brucella are facultative intracellular bacteria that chronically infect humans
      and animals causing brucellosis. Brucella are able to invade and replicate in a
      broad range of cell lines in vitro, however the cells supporting bacterial growth
      in vivo are largely unknown. In order to identify these, we used a Brucella
      melitensis strain stably expressing mCherry fluorescent protein to determine the
      phenotype of infected cells in spleen and liver, two major sites of B. melitensis
      growth in mice. In both tissues, the majority of primary infected cells expressed
      the F4/80 myeloid marker. The peak of infection correlated with granuloma
      development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells
      expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c
      marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of
      genetically deficient mice revealed that differentiation of iNOS+ inflammatory
      DC, granuloma formation and control of bacterial growth were deeply affected by
      the absence of MyD88, IL-12p35 and IFN-gamma molecules. During chronic phase of
      infection in susceptible mice, we identified a particular subset of DC expressing
      both CD11c and CD205, serving as a reservoir for the bacteria. Taken together,
      our results describe the cellular nature of immune effectors involved during
      Brucella infection and reveal a previously unappreciated role for DC subsets,
      both as effectors and reservoir cells, in the pathogenesis of brucellosis.

PMID- 22479179
TI  - Mutation and selection of prions.

PMID- 22479180
TI  - C. elegans germ cells show temperature and age-dependent expression of Cer1, a
      Gypsy/Ty3-related retrotransposon.
AB  - Virus-like particles (VLPs) have not been observed in Caenorhabditis germ cells,
      although nematode genomes contain low numbers of retrotransposon and retroviral
      sequences. We used electron microscopy to search for VLPs in various wild strains
      of Caenorhabditis, and observed very rare candidate VLPs in some strains,
      including the standard laboratory strain of C. elegans, N2. We identified the N2
      VLPs as capsids produced by Cer1, a retrotransposon in the Gypsy/Ty3 family of
      retroviruses/retrotransposons. Cer1 expression is age and temperature dependent,
      with abundant expression at 15 degrees C and no detectable expression at 25
      degrees C, explaining how VLPs escaped detection in previous studies. Similar age
      and temperature-dependent expression of Cer1 retrotransposons was observed for
      several other wild strains, indicating that these properties are common, if not
      integral, features of this retroelement. Retrotransposons, in contrast to DNA
      transposons, have a cytoplasmic stage in replication, and those that infect non
      dividing cells must pass their genomic material through nuclear pores. In most C.
      elegans germ cells, nuclear pores are largely covered by germline-specific
      organelles called P granules. Our results suggest that Cer1 capsids target
      meiotic germ cells exiting pachytene, when free nuclear pores are added to the
      nuclear envelope and existing P granules begin to be removed. In pachytene germ
      cells, Cer1 capsids concentrate away from nuclei on a subset of microtubules that
      are exceptionally resistant to microtubule inhibitors; the capsids can aggregate
      these stable microtubules in older adults, which exhibit a temperature-dependent
      decrease in egg viability. When germ cells exit pachytene, the stable
      microtubules disappear and capsids redistribute close to nuclei that have P
      granule-free nuclear pores. This redistribution is microtubule dependent,
      suggesting that capsids that are released from stable microtubules transfer onto
      new, dynamic microtubules to track toward nuclei. These studies introduce C.
      elegans as a model to study the interplay between retroelements and germ cell
      biology.

PMID- 22479181
TI  - A novel mouse model of Schistosoma haematobium egg-induced immunopathology.
AB  - Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a
      major source of morbidity and mortality for more than 112 million people
      worldwide. Infection with S. haematobium results in a variety of immunopathologic
      sequelae caused by parasite oviposition within the urinary tract, which drives
      inflammation, hematuria, fibrosis, bladder dysfunction, and increased
      susceptibility to urothelial carcinoma. While humans readily develop urogenital
      schistosomiasis, the lack of an experimentally-tractable model has greatly
      impaired our understanding of the mechanisms that underlie this important
      disease. We have developed an improved mouse model of S. haematobium urinary
      tract infection that recapitulates several aspects of human urogenital
      schistosomiasis. Following microinjection of purified S. haematobium eggs into
      the bladder wall, mice consistently develop macrophage-rich granulomata that
      persist for at least 3 months and pass eggs in their urine. Importantly, egg
      injected mice also develop urinary tract fibrosis, bladder dysfunction, and
      various urothelial changes morphologically reminiscent of human urogenital
      schistosomiasis. As expected, S. haematobium egg-induced immune responses in the
      immediate microenvironment, draining lymph nodes, and systemic circulation are
      associated with a Type 2-dominant inflammatory response, characterized by high
      levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse
      model may help facilitate a better understanding of the unique pathophysiological
      mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated
      with urogenital schistosomiasis.

PMID- 22479182
TI  - A cytoplasmic tail determinant in HIV-1 Vpu mediates targeting of tetherin for
      endosomal degradation and counteracts interferon-induced restriction.
AB  - The HIV-1 accessory protein Vpu counteracts tetherin (BST-2/CD317) by preventing
      its incorporation into virions, reducing its surface expression, and ultimately
      promoting its degradation. Here we characterize a putative trafficking motif,
      EXXXLV, in the second alpha helix of the subtype-B Vpu cytoplasmic tail as being
      required for efficient tetherin antagonism. Mutation of this motif prevents ESCRT
      dependent degradation of tetherin/Vpu complexes, tetherin cell surface
      downregulation, but not its physical interaction with Vpu. Importantly, this
      motif is required for efficient cell-free virion release from CD4+ T cells,
      particularly after their exposure to type-1 interferon, indicating that the
      ability to reduce surface tetherin levels and promote its degradation is
      important to counteract restriction under conditions that the virus likely
      encounters in vivo. Vpu EXXXLV mutants accumulate with tetherin at the cell
      surface and in endosomal compartments, but retain the ability to bind both beta
      TrCP2 and HRS, indicating that this motif is required for a post-binding
      trafficking event that commits tetherin for ESCRT-dependent degradation and
      prevents its transit to the plasma membrane and viral budding zones. We further
      found that while Vpu function is dependent on clathrin, and the entire second
      alpha helix of the Vpu tail can be functionally complemented by a clathrin
      adaptor binding peptide derived from HIV-1 Nef, none of the canonical clathrin
      adaptors nor retromer are required for this process. Finally we show that
      residual activity of Vpu EXXXLV mutants requires an intact endocytic motif in
      tetherin, suggesting that physical association of Vpu with tetherin during its
      recycling may be sufficient to compromise tetherin activity to some degree.

PMID- 22479183
TI  - HIV-1 superinfection in women broadens and strengthens the neutralizing antibody
      response.
AB  - Identifying naturally-occurring neutralizing antibodies (NAb) that are cross
      reactive against all global subtypes of HIV-1 is an important step toward the
      development of a vaccine. Establishing the host and viral determinants for
      eliciting such broadly NAbs is also critical for immunogen design. NAb breadth
      has previously been shown to be positively associated with viral diversity.
      Therefore, we hypothesized that superinfected individuals develop a broad NAb
      response as a result of increased antigenic stimulation by two distinct viruses.
      To test this hypothesis, plasma samples from 12 superinfected women each assigned
      to three singly infected women were tested against a panel of eight viruses
      representing four different HIV-1 subtypes at matched time points post
      superinfection (~5 years post-initial infection). Here we show superinfected
      individuals develop significantly broader NAb responses post-superinfection when
      compared to singly infected individuals (RR = 1.68, CI: 1.23-2.30, p = 0.001).
      This was true even after controlling for NAb breadth developed prior to
      superinfection, contemporaneous CD4+ T cell count and viral load. Similarly, both
      unadjusted and adjusted analyses showed significantly greater potency in
      superinfected cases compared to controls. Notably, two superinfected individuals
      were able to neutralize variants from four different subtypes at plasma dilutions
      >1?300, suggesting that their NAbs exhibit elite activity. Cross-subtype breadth
      was detected within a year of superinfection in both of these individuals, which
      was within 1.5 years of their initial infection. These data suggest that
      sequential infections lead to augmentation of the NAb response, a process that
      may provide insight into potential mechanisms that contribute to the development
      of antibody breadth. Therefore, a successful vaccination strategy that mimics
      superinfection may lead to the development of broad NAbs in immunized
      individuals.

PMID- 22479184
TI  - Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated
      protein.
AB  - The principal virulence determinant of Mycobacterium tuberculosis (Mtb), the ESX
      1 protein secretion system, is positively controlled at the transcriptional level
      by EspR. Depletion of EspR reportedly affects a small number of genes, both
      positively or negatively, including a key ESX-1 component, the espACD operon.
      EspR is also thought to be an ESX-1 substrate. Using EspR-specific antibodies in
      ChIP-Seq experiments (chromatin immunoprecipitation followed by ultra-high
      throughput DNA sequencing) we show that EspR binds to at least 165 loci on the
      Mtb genome. Included in the EspR regulon are genes encoding not only EspA, but
      also EspR itself, the ESX-2 and ESX-5 systems, a host of diverse cell wall
      functions, such as production of the complex lipid PDIM (phenolthiocerol
      dimycocerosate) and the PE/PPE cell-surface proteins. EspR binding sites are not
      restricted to promoter regions and can be clustered. This suggests that rather
      than functioning as a classical regulatory protein EspR acts globally as a
      nucleoid-associated protein capable of long-range interactions consistent with a
      recently established structural model. EspR expression was shown to be growth
      phase-dependent, peaking in the stationary phase. Overexpression in Mtb strain
      H37Rv revealed that EspR influences target gene expression both positively or
      negatively leading to growth arrest. At no stage was EspR secreted into the
      culture filtrate. Thus, rather than serving as a specific activator of a
      virulence locus, EspR is a novel nucleoid-associated protein, with both
      architectural and regulatory roles, that impacts cell wall functions and
      pathogenesis through multiple genes.

PMID- 22479185
TI  - Dengue virus infection of the Aedes aegypti salivary gland and chemosensory
      apparatus induces genes that modulate infection and blood-feeding behavior.
AB  - The female Aedes aegypti salivary gland plays a pivotal role in bloodmeal
      acquisition and reproduction, and thereby dengue virus (DENV) transmission. It
      produces numerous immune factors, as well as immune-modulatory, vasodilatory, and
      anti-coagulant molecules that facilitate blood-feeding. To assess the impact of
      DENV infection on salivary gland physiology and function, we performed a
      comparative genome-wide microarray analysis of the naive and DENV infection
      responsive A. aegypti salivary gland transcriptomes. DENV infection resulted in
      the regulation of 147 transcripts that represented a variety of functional
      classes, including several that are essential for virus transmission, such as
      immunity, blood-feeding, and host-seeking. RNAi-mediated gene silencing of three
      DENV infection-responsive genes--a cathepsin B, a putative cystatin, and a
      hypothetical ankyrin repeat-containing protein--significantly modulated DENV
      replication in the salivary gland. Furthermore, silencing of two DENV infection
      responsive odorant-binding protein genes (OBPs) resulted in an overall compromise
      in blood acquisition from a single host by increasing the time for initiation of
      probing and the probing time before a successful bloodmeal. We also show that
      DENV established an extensive infection in the mosquito's main olfactory organs,
      the antennae, which resulted in changes of the transcript abundance of key host
      seeking genes. DENV infection, however, did not significantly impact probing
      initiation or probing times in our laboratory infection system. Here we show for
      the first time that the mosquito salivary gland mounts responses to suppress DENV
      which, in turn, modulates the expression of chemosensory-related genes that
      regulate feeding behavior. These reciprocal interactions may have the potential
      to affect DENV transmission between humans.

PMID- 22479186
TI  - Shiga toxin 1 induces on lipopolysaccharide-treated astrocytes the release of
      tumor necrosis factor-alpha that alter brain-like endothelium integrity.
AB  - The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia,
      thrombocytopenia and renal dysfunction. The typical form of HUS is generally
      associated with infections by Gram-negative Shiga toxin (Stx)-producing
      Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but
      bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the
      pathophysiology. Although renal failure is characteristic of this syndrome,
      neurological complications occur in severe cases and is usually associated with
      death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral
      endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory
      cells in the brain and determine the BBB function. ASTs are in close proximity to
      ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of
      their response on ECs is essential. We have previously demonstrated that Stx1 and
      LPS induced activation of rat ASTs and the release of inflammatory factors such
      as TNF-alpha, nitric oxide and chemokines. Here, we demonstrate that rat ASTs
      derived factors alter permeability of ECs with brain properties (HUVECd);
      suggesting that functional properties of BBB could also be affected.
      Additionally, these factors activate HUVECd and render them into a proagregant
      state promoting PMN and platelets adhesion. Moreover, these effects were
      dependent on ASTs secreted-TNF-alpha. Stx1 and LPS-induced ASTs response could
      influence brain ECs integrity and BBB function once Stx and factors associated to
      the STEC infection reach the brain parenchyma and therefore contribute to the
      development of the neuropathology observed in HUS.

PMID- 22479187
TI  - Anthrax lethal factor cleavage of Nlrp1 is required for activation of the
      inflammasome.
AB  - NOD-like receptor (NLR) proteins (Nlrps) are cytosolic sensors responsible for
      detection of pathogen and danger-associated molecular patterns through unknown
      mechanisms. Their activation in response to a wide range of intracellular danger
      signals leads to formation of the inflammasome, caspase-1 activation, rapid
      programmed cell death (pyroptosis) and maturation of IL-1beta and IL-18. Anthrax
      lethal toxin (LT) induces the caspase-1-dependent pyroptosis of mouse and rat
      macrophages isolated from certain inbred rodent strains through activation of the
      NOD-like receptor (NLR) Nlrp1 inflammasome. Here we show that LT cleaves rat
      Nlrp1 and this cleavage is required for toxin-induced inflammasome activation, IL
      1 beta release, and macrophage pyroptosis. These results identify both a
      previously unrecognized mechanism of activation of an NLR and a new,
      physiologically relevant protein substrate of LT.

PMID- 22479188
TI  - A quantitative, high-throughput reverse genetic screen reveals novel connections
      between Pre-mRNA splicing and 5' and 3' end transcript determinants.
AB  - Here we present the development and implementation of a genome-wide reverse
      genetic screen in the budding yeast, Saccharomyces cerevisiae, that couples high
      throughput strain growth, robotic RNA isolation and cDNA synthesis, and
      quantitative PCR to allow for a robust determination of the level of nearly any
      cellular RNA in the background of ~5,500 different mutants. As an initial test of
      this approach, we sought to identify the full complement of factors that impact
      pre-mRNA splicing. Increasing lines of evidence suggest a relationship between
      pre-mRNA splicing and other cellular pathways including chromatin remodeling,
      transcription, and 3' end processing, yet in many cases the specific proteins
      responsible for functionally connecting these pathways remain unclear. Moreover,
      it is unclear whether all pathways that are coupled to splicing have been
      identified. As expected, our approach sensitively detects pre-mRNA accumulation
      in the vast majority of strains containing mutations in known splicing factors.
      Remarkably, however, several additional candidates were found to cause increases
      in pre-mRNA levels similar to that seen for canonical splicing mutants, none of
      which had previously been implicated in the splicing pathway. Instead, several of
      these factors have been previously implicated to play roles in chromatin
      remodeling, 3' end processing, and other novel categories. Further analysis of
      these factors using splicing-sensitive microarrays confirms that deletion of
      Bdf1, a factor that links transcription initiation and chromatin remodeling,
      leads to a global splicing defect, providing evidence for a novel connection
      between pre-mRNA splicing and this component of the SWR1 complex. By contrast,
      mutations in 3' end processing factors such as Cft2 and Yth1 also result in pre
      mRNA splicing defects, although only for a subset of transcripts, suggesting that
      spliceosome assembly in S. cerevisiae may more closely resemble mammalian models
      of exon-definition. More broadly, our work demonstrates the capacity of this
      approach to identify novel regulators of various cellular RNAs.

PMID- 22479189
TI  - LMW-E/CDK2 deregulates acinar morphogenesis, induces tumorigenesis, and
      associates with the activated b-Raf-ERK1/2-mTOR pathway in breast cancer
      patients.
AB  - Elastase-mediated cleavage of cyclin E generates low molecular weight cyclin E
      (LMW-E) isoforms exhibiting enhanced CDK2-associated kinase activity and
      resistance to inhibition by CDK inhibitors p21 and p27. Approximately 27% of
      breast cancers express high LMW-E protein levels, which significantly correlates
      with poor survival. The objective of this study was to identify the signaling
      pathway(s) deregulated by LMW-E expression in breast cancer patients and to
      identify pharmaceutical agents to effectively target this pathway. Ectopic LMW-E
      expression in nontumorigenic human mammary epithelial cells (hMECs) was
      sufficient to generate xenografts with greater tumorigenic potential than full
      length cyclin E, and the tumorigenicity was augmented by in vivo passaging.
      However, cyclin E mutants unable to interact with CDK2 protected hMECs from tumor
      development. When hMECs were cultured on Matrigel, LMW-E mediated aberrant acinar
      morphogenesis, including enlargement of acinar structures and formation of multi
      acinar complexes, as denoted by reduced BIM and elevated Ki67 expression.
      Similarly, inducible expression of LMW-E in transgenic mice generated hyper
      proliferative terminal end buds resulting in enhanced mammary tumor development.
      Reverse-phase protein array assay of 276 breast tumor patient samples and cells
      cultured on monolayer and in three-dimensional Matrigel demonstrated that, in
      terms of protein expression profile, hMECs cultured in Matrigel more closely
      resembled patient tissues than did cells cultured on monolayer. Additionally, the
      b-Raf-ERK1/2-mTOR pathway was activated in LMW-E-expressing patient samples, and
      activation of this pathway was associated with poor disease-specific survival.
      Combination treatment using roscovitine (CDK inhibitor) plus either rapamycin
      (mTOR inhibitor) or sorafenib (a pan kinase inhibitor targeting b-Raf)
      effectively prevented aberrant acinar formation in LMW-E-expressing cells by
      inducing G1/S cell cycle arrest. LMW-E requires CDK2-associated kinase activity
      to induce mammary tumor formation by disrupting acinar development. The b-Raf
      ERK1/2-mTOR signaling pathway is aberrantly activated in breast cancer and can be
      suppressed by combination treatment with roscovitine plus either rapamycin or
      sorafenib.

PMID- 22479190
TI  - Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle
      orientation, mitotic progression, and maintenance of neural progenitor cells.
AB  - The cerebral cortex is a specialized region of the brain that processes
      cognitive, motor, somatosensory, auditory, and visual functions. Its
      characteristic architecture and size is dependent upon the number of neurons
      generated during embryogenesis and has been postulated to be governed by
      symmetric versus asymmetric cell divisions, which mediate the balance between
      progenitor cell maintenance and neuron differentiation, respectively. The
      mechanistic importance of spindle orientation remains controversial, hence there
      is considerable interest in understanding how neural progenitor cell mitosis is
      controlled during neurogenesis. We discovered that Treacle, which is encoded by
      the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is
      critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of
      function disrupts spindle orientation and cell cycle progression, which perturbs
      the maintenance, proliferation, and localization of neural progenitors during
      cortical neurogenesis. Consistent with this, Tcof1(+/-) mice exhibit reduced
      brain size as a consequence of defects in neural progenitor maintenance. We
      determined that Treacle elicits its effect via a direct interaction with Polo
      like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1
      in governing mitotic progression and spindle orientation in the developing
      mammalian cortex. Increased asymmetric cell division, however, did not promote
      increased neuronal differentiation. Collectively our research has therefore
      identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity,
      mitotic progression, and proliferation in the maintenance and localization of
      neural progenitor cells. Together, Treacle and Plk1 are critically required for
      proper cortical neurogenesis, which has important implications in the regulation
      of mammalian brain size and the pathogenesis of congenital neurodevelopmental
      disorders such as microcephaly.

PMID- 22479193
TI  - Phenotypic plasticity of the Drosophila transcriptome.
AB  - Phenotypic plasticity is the ability of a single genotype to produce different
      phenotypes in response to changing environments. We assessed variation in genome
      wide gene expression and four fitness-related phenotypes of an outbred Drosophila
      melanogaster population under 20 different physiological, social, nutritional,
      chemical, and physical environments; and we compared the phenotypically plastic
      transcripts to genetically variable transcripts in a single environment. The
      environmentally sensitive transcriptome consists of two transcript categories,
      which comprise ~15% of expressed transcripts. Class I transcripts are genetically
      variable and associated with detoxification, metabolism, proteolysis, heat shock
      proteins, and transcriptional regulation. Class II transcripts have low genetic
      variance and show sexually dimorphic expression enriched for reproductive
      functions. Clustering analysis of Class I transcripts reveals a fragmented
      modular organization and distinct environmentally responsive transcriptional
      signatures for the four fitness-related traits. Our analysis suggests that a
      restricted environmentally responsive segment of the transcriptome preserves the
      balance between phenotypic plasticity and environmental canalization.

PMID- 22479192
TI  - Intronic cis-regulatory modules mediate tissue-specific and microbial control of
      angptl4/fiaf transcription.
AB  - The intestinal microbiota enhances dietary energy harvest leading to increased
      fat storage in adipose tissues. This effect is caused in part by the microbial
      suppression of intestinal epithelial expression of a circulating inhibitor of
      lipoprotein lipase called Angiopoietin-like 4 (Angptl4/Fiaf). To define the cis
      regulatory mechanisms underlying intestine-specific and microbial control of
      Angptl4 transcription, we utilized the zebrafish system in which host regulatory
      DNA can be rapidly analyzed in a live, transparent, and gnotobiotic vertebrate.
      We found that zebrafish angptl4 is transcribed in multiple tissues including the
      liver, pancreatic islet, and intestinal epithelium, which is similar to its
      mammalian homologs. Zebrafish angptl4 is also specifically suppressed in the
      intestinal epithelium upon colonization with a microbiota. In vivo transgenic
      reporter assays identified discrete tissue-specific regulatory modules within
      angptl4 intron 3 sufficient to drive expression in the liver, pancreatic islet
      beta-cells, or intestinal enterocytes. Comparative sequence analyses and
      heterologous functional assays of angptl4 intron 3 sequences from 12 teleost fish
      species revealed differential evolution of the islet and intestinal regulatory
      modules. High-resolution functional mapping and site-directed mutagenesis defined
      the minimal set of regulatory sequences required for intestinal activity.
      Strikingly, the microbiota suppressed the transcriptional activity of the
      intestine-specific regulatory module similar to the endogenous angptl4 gene.
      These results suggest that the microbiota might regulate host intestinal Angptl4
      protein expression and peripheral fat storage by suppressing the activity of an
      intestine-specific transcriptional enhancer. This study provides a useful
      paradigm for understanding how microbial signals interact with tissue-specific
      regulatory networks to control the activity and evolution of host gene
      transcription.

PMID- 22479194
TI  - PIF4-mediated activation of YUCCA8 expression integrates temperature into the
      auxin pathway in regulating arabidopsis hypocotyl growth.
AB  - Higher plants adapt their growth to high temperature by a dramatic change in
      plant architecture. It has been shown that the transcriptional regulator
      phytochrome-interacting factor 4 (PIF4) and the phytohormone auxin are involved
      in the regulation of high temperature-induced hypocotyl elongation in
      Arabidopsis. Here we report that PIF4 regulates high temperature-induced
      hypocotyl elongation through direct activation of the auxin biosynthetic gene
      YUCCA8 (YUC8). We show that high temperature co-upregulates the transcript
      abundance of PIF4 and YUC8. PIF4-dependency of high temperature-mediated
      induction of YUC8 expression as well as auxin biosynthesis, together with the
      finding that overexpression of PIF4 leads to increased expression of YUC8 and
      elevated free IAA levels in planta, suggests a possibility that PIF4 directly
      activates YUC8 expression. Indeed, gel shift and chromatin immunoprecipitation
      experiments demonstrate that PIF4 associates with the G-box-containing promoter
      region of YUC8. Transient expression assay in Nicotiana benthamiana leaves
      support that PIF4 directly activates YUC8 expression in vivo. Significantly, we
      show that the yuc8 mutation can largely suppress the long-hypocotyl phenotype of
      PIF4-overexpression plants and also can reduce high temperature-induced hypocotyl
      elongation. Genetic analyses reveal that the shy2-2 mutation, which harbors a
      stabilized mutant form of the IAA3 protein and therefore is defective in high
      temperature-induced hypocotyl elongation, largely suppresses the long-hypocotyl
      phenotype of PIF4-overexpression plants. Taken together, our results illuminate a
      molecular framework by which the PIF4 transcriptional regulator integrates its
      action into the auxin pathway through activating the expression of specific auxin
      biosynthetic gene. These studies advance our understanding on the molecular
      mechanism underlying high temperature-induced adaptation in plant architecture.

PMID- 22479191
TI  - Genome-wide association and functional follow-up reveals new loci for kidney
      function.
AB  - Chronic kidney disease (CKD) is an important public health problem with a genetic
      component. We performed genome-wide association studies in up to 130,600 European
      ancestry participants overall, and stratified for key CKD risk factors. We
      uncovered 6 new loci in association with estimated glomerular filtration rate
      (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1,
      CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish
      embryos revealed podocyte and tubular abnormalities with altered dextran
      clearance, suggesting a role for these genes in renal function. By providing new
      insights into genes that regulate renal function, these results could further our
      understanding of the pathogenesis of CKD.

PMID- 22479195
TI  - The transcription factor ultraspiracle influences honey bee social behavior and
      behavior-related gene expression.
AB  - Behavior is among the most dynamic animal phenotypes, modulated by a variety of
      internal and external stimuli. Behavioral differences are associated with large
      scale changes in gene expression, but little is known about how these changes are
      regulated. Here we show how a transcription factor (TF), ultraspiracle (usp; the
      insect homolog of the Retinoid X Receptor), working in complex transcriptional
      networks, can regulate behavioral plasticity and associated changes in gene
      expression. We first show that RNAi knockdown of USP in honey bee abdominal fat
      bodies delayed the transition from working in the hive (primarily "nursing"
      brood) to foraging outside. We then demonstrate through transcriptomics
      experiments that USP induced many maturation-related transcriptional changes in
      the fat bodies by mediating transcriptional responses to juvenile hormone. These
      maturation-related transcriptional responses to USP occurred without changes in
      USP's genomic binding sites, as revealed by ChIP-chip. Instead, behaviorally
      related gene expression is likely determined by combinatorial interactions
      between USP and other TFs whose cis-regulatory motifs were enriched at USP's
      binding sites. Many modules of JH- and maturation-related genes were co-regulated
      in both the fat body and brain, predicting that usp and cofactors influence
      shared transcriptional networks in both of these maturation-related tissues. Our
      findings demonstrate how "single gene effects" on behavioral plasticity can
      involve complex transcriptional networks, in both brain and peripheral tissues.

PMID- 22479196
TI  - Critical evaluation of imprinted gene expression by RNA-Seq: a new perspective.
AB  - In contrast to existing estimates of approximately 200 murine imprinted genes,
      recent work based on transcriptome sequencing uncovered parent-of-origin allelic
      effects at more than 1,300 loci in the developing brain and two adult brain
      regions, including hundreds present in only males or females. Our independent
      replication of the embryonic brain stage, where the majority of novel imprinted
      genes were discovered and the majority of previously known imprinted genes
      confirmed, resulted in only 12.9% concordance among the novel imprinted loci.
      Further analysis and pyrosequencing-based validation revealed that the vast
      majority of the novel reported imprinted loci are false-positives explained by
      technical and biological variation of the experimental approach. We show that
      allele-specific expression (ASE) measured with RNA-Seq is not accurately modeled
      with statistical methods that assume random independent sampling and that
      systematic error must be accounted for to enable accurate identification of
      imprinted expression. Application of a robust approach that accounts for these
      effects revealed 50 candidate genes where allelic bias was predicted to be parent
      of-origin-dependent. However, 11 independent validation attempts through a range
      of allelic expression biases confirmed only 6 of these novel cases. The results
      emphasize the importance of independent validation and suggest that the number of
      imprinted genes is much closer to the initial estimates.

PMID- 22479197
TI  - Imprinted genes ... and the number is?

PMID- 22479198
TI  - The atypical calpains: evolutionary analyses and roles in Caenorhabditis elegans
      cellular degeneration.
AB  - The calpains are physiologically important Ca(2+)-activated regulatory proteases,
      which are divided into typical or atypical sub-families based on constituent
      domains. Both sub-families are present in mammals, but our understanding of
      calpain function is based primarily on typical sub-family members. Here, we take
      advantage of the model organism Caenorhabditis elegans, which expresses only
      atypical calpains, to extend our knowledge of the phylogenetic evolution and
      function of calpains. We provide evidence that a typical human calpain protein
      with a penta EF hand, detected using custom profile hidden Markov models, is
      conserved in ancient metazoans and a divergent clade. These analyses also provide
      evidence for the lineage-specific loss of typical calpain genes in C. elegans and
      Ciona, and they reveal that many calpain-like genes lack an intact catalytic
      triad. Given the association between the dysregulation of typical calpains and
      human degenerative pathologies, we explored the phenotypes, expression profiles,
      and consequences of inappropriate reduction or activation of C. elegans atypical
      calpains. These studies show that the atypical calpain gene, clp-1, contributes
      to muscle degeneration and reveal that clp-1 activity is sensitive to genetic
      manipulation of [Ca(2+)](i). We show that CLP-1 localizes to sarcomeric sub
      structures, but is excluded from dense bodies (Z-disks). We find that the muscle
      degeneration observed in a C. elegans model of dystrophin-based muscular
      dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A
      inhibition of the EGL-19 calcium channel reveals that Ca(2+) dysfunction
      underlies the C. elegans MyoD model of myopathy. Taken together, our analyses
      highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and
      suggest that the atypical calpains could retain conserved roles in myofilament
      turnover.

PMID- 22479199
TI  - Balanced codon usage optimizes eukaryotic translational efficiency.
AB  - Cellular efficiency in protein translation is an important fitness determinant in
      rapidly growing organisms. It is widely believed that synonymous codons are
      translated with unequal speeds and that translational efficiency is maximized by
      the exclusive use of rapidly translated codons. Here we estimate the in vivo
      translational speeds of all sense codons from the budding yeast Saccharomyces
      cerevisiae. Surprisingly, preferentially used codons are not translated faster
      than unpreferred ones. We hypothesize that this phenomenon is a result of codon
      usage in proportion to cognate tRNA concentrations, the optimal strategy in
      enhancing translational efficiency under tRNA shortage. Our predicted codon-tRNA
      balance is indeed observed from all model eukaryotes examined, and its impact on
      translational efficiency is further validated experimentally. Our study reveals a
      previously unsuspected mechanism by which unequal codon usage increases
      translational efficiency, demonstrates widespread natural selection for
      translational efficiency, and offers new strategies to improve synthetic biology.

PMID- 22479200
TI  - Gene reactivation by 5-aza-2'-deoxycytidine-induced demethylation requires SRCAP
      mediated H2A.Z insertion to establish nucleosome depleted regions.
AB  - 5-Aza-2'-deoxycytidine, approved by the FDA for the treatment of myelodysplastic
      syndrome (MDS), is incorporated into the DNA of dividing cells where it
      specifically inhibits DNA methylation by forming covalent complexes with the DNA
      methyltransferases (DNMTs). In an effort to study the correlations between DNA
      methylation, nucleosome remodeling, and gene reactivation, we investigate the
      integrated epigenetic events that worked coordinately to reprogram the methylated
      and closed promoters back to permissive chromatin configurations after 5-Aza-2'
      deoxycytidine treatment. The ChIP results indicate that H2A.Z is deposited at
      promoter regions by the Snf2-related CBP activator protein (SRCAP) complex
      following DNA demethylation. According to our genome-wide expression and DNA
      methylation profiles, we find that the complete re-activation of silenced genes
      requires the insertion of the histone variant H2A.Z, which facilitates the
      acquisition of regions fully depleted of nucleosome as demonstrated by NOMe-seq
      (Nucleosome Occupancy Methylome-sequencing) assay. In contrast, SRCAP-mediated
      H2A.Z deposition is not required for maintaining the active status of
      constitutively expressed genes. By combining Hpa II digestion with NOMe-seq
      assay, we show that hemimethylated DNA, which is generated following drug
      incorporation, remains occupied by nucleosomes. Our data highlight H2A.Z as a
      novel and essential factor involved in 5-Aza-2'-deoxycytidine-induced gene
      reactivation. Furthermore, we elucidate that chromatin remodeling translates the
      demethylation ability of DNMT inhibitors to their downstream efficacies,
      suggesting future therapeutic implications for chromatin remodelers.

PMID- 22479201
TI  - The ciliogenic transcription factor RFX3 regulates early midline distribution of
      guidepost neurons required for corpus callosum development.
AB  - The corpus callosum (CC) is the major commissure that bridges the cerebral
      hemispheres. Agenesis of the CC is associated with human ciliopathies, but the
      origin of this default is unclear. Regulatory Factor X3 (RFX3) is a transcription
      factor involved in the control of ciliogenesis, and Rfx3-deficient mice show
      several hallmarks of ciliopathies including left-right asymmetry defects and
      hydrocephalus. Here we show that Rfx3-deficient mice suffer from CC agenesis
      associated with a marked disorganisation of guidepost neurons required for axon
      pathfinding across the midline. Using transplantation assays, we demonstrate that
      abnormalities of the mutant midline region are primarily responsible for the CC
      malformation. Conditional genetic inactivation shows that RFX3 is not required in
      guidepost cells for proper CC formation, but is required before E12.5 for proper
      patterning of the cortical septal boundary and hence accurate distribution of
      guidepost neurons at later stages. We observe focused but consistent ectopic
      expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate
      associated with a reduced ratio of GLIoma-associated oncogene family zinc finger
      3 (GLI3) repressor to activator forms. We demonstrate on brain explant cultures
      that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3
      mutants. This study unravels a crucial role of RFX3 during early brain
      development by indirectly regulating GLI3 activity, which leads to FGF8
      upregulation and ultimately to disturbed distribution of guidepost neurons
      required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel
      understandings of the mechanisms that underlie CC agenesis in ciliopathies.

PMID- 22479203
TI  - Statistical analysis of readthrough levels for nonsense mutations in mammalian
      cells reveals a major determinant of response to gentamicin.
AB  - The efficiency of translation termination depends on the nature of the stop codon
      and the surrounding nucleotides. Some molecules, such as aminoglycoside
      antibiotics (gentamicin), decrease termination efficiency and are currently being
      evaluated for diseases caused by premature termination codons. However, the
      readthrough response to treatment is highly variable and little is known about
      the rules governing readthrough level and response to aminoglycosides. In this
      study, we carried out in-depth statistical analysis on a very large set of
      nonsense mutations to decipher the elements of nucleotide context responsible for
      modulating readthrough levels and gentamicin response. We quantified readthrough
      for 66 sequences containing a stop codon, in the presence and absence of
      gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of
      readthrough after treatment is determined by the complex interplay between the
      stop codon and a larger sequence context. There was a strong positive correlation
      between basal and induced readthrough levels, and a weak negative correlation
      between basal readthrough level and gentamicin response (i.e. the factor of
      increase from basal to induced readthrough levels). The identity of the stop
      codon did not affect the response to gentamicin treatment. In agreement with a
      previous report, we confirm that the presence of a cytosine in +4 position
      promotes higher basal and gentamicin-induced readthrough than other nucleotides.
      We highlight for the first time that the presence of a uracil residue immediately
      upstream from the stop codon is a major determinant of the response to
      gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather
      than by the amino-acid or tRNA corresponding to the -1 codon. Finally, we point
      out that a uracil at this position associated with a cytosine at +4 results in an
      optimal gentamicin-induced readthrough, which is the therapeutically relevant
      variable.

PMID- 22479204
TI  - Igf1r signaling is indispensable for preimplantation development and is activated
      via a novel function of E-cadherin.
AB  - Insulin-like growth factor I receptor (Igf1r) signaling controls proliferation,
      differentiation, growth, and cell survival in many tissues; and its deregulated
      activity is involved in tumorigenesis. Although important during fetal growth and
      postnatal life, a function for the Igf pathway during preimplantation development
      has not been described. We show that abrogating Igf1r signaling with specific
      inhibitors blocks trophectoderm formation and compromises embryo survival during
      murine blastocyst formation. In normal embryos total Igf1r is present throughout
      the membrane, whereas the activated form is found exclusively at cell contact
      sites, colocalizing with E-cadherin. Using genetic domain switching, we show a
      requirement for E-cadherin to maintain proper activation of Igf1r. Embryos
      expressing exclusively a cadherin chimera with N-cadherin extracellular and E
      cadherin intracellular domains (NcEc) fail to form a trophectoderm and cells die
      by apoptosis. In contrast, homozygous mutant embryos expressing a reverse
      structured chimera (EcNc) show trophectoderm survival and blastocoel cavitation,
      indicating a crucial and non-substitutable role of the E-cadherin ectodomain for
      these processes. Strikingly, blastocyst formation can be rescued in homozygous
      NcEc embryos by restoring Igf1r signaling, which enhances cell survival. Hence,
      perturbation of E-cadherin extracellular integrity, independent of its cell
      adhesion function, blocked Igf1r signaling and induced cell death in the
      trophectoderm. Our results reveal an important and yet undiscovered function of
      Igf1r during preimplantation development mediated by a unique physical
      interaction between Igf1r and E-cadherin indispensable for proper receptor
      activation and anti-apoptotic signaling. We provide novel insights into how
      ligand-dependent Igf1r activity is additionally gated to sense developmental
      potential in utero and into a bifunctional role of adhesion molecules in contact
      formation and signaling.

PMID- 22479205
TI  - Accurate prediction of inducible transcription factor binding intensities in
      vivo.
AB  - DNA sequence and local chromatin landscape act jointly to determine transcription
      factor (TF) binding intensity profiles. To disentangle these influences, we
      developed an experimental approach, called protein/DNA binding followed by high
      throughput sequencing (PB-seq), that allows the binding energy landscape to be
      characterized genome-wide in the absence of chromatin. We applied our methods to
      the Drosophila Heat Shock Factor (HSF), which inducibly binds a target DNA
      sequence element (HSE) following heat shock stress. PB-seq involves incubating
      sheared naked genomic DNA with recombinant HSF, partitioning the HSF-bound and
      HSF-free DNA, and then detecting HSF-bound DNA by high-throughput sequencing. We
      compared PB-seq binding profiles with ones observed in vivo by ChIP-seq and
      developed statistical models to predict the observed departures from idealized
      binding patterns based on covariates describing the local chromatin environment.
      We found that DNase I hypersensitivity and tetra-acetylation of H4 were the most
      influential covariates in predicting changes in HSF binding affinity. We also
      investigated the extent to which DNA accessibility, as measured by digital DNase
      I footprinting data, could be predicted from MNase-seq data and the ChIP-chip
      profiles for many histone modifications and TFs, and found GAGA element
      associated factor (GAF), tetra-acetylation of H4, and H4K16 acetylation to be the
      most predictive covariates. Lastly, we generated an unbiased model of HSF binding
      sequences, which revealed distinct biophysical properties of the HSF/HSE
      interaction and a previously unrecognized substructure within the HSE. These
      findings provide new insights into the interplay between the genomic sequence and
      the chromatin landscape in determining transcription factor binding intensity.

PMID- 22479206
TI  - Metabolic profiling of a mapping population exposes new insights in the
      regulation of seed metabolism and seed, fruit, and plant relations.
AB  - To investigate the regulation of seed metabolism and to estimate the degree of
      metabolic natural variability, metabolite profiling and network analysis were
      applied to a collection of 76 different homozygous tomato introgression lines
      (ILs) grown in the field in two consecutive harvest seasons. Factorial ANOVA
      confirmed the presence of 30 metabolite quantitative trait loci (mQTL). Amino
      acid contents displayed a high degree of variability across the population, with
      similar patterns across the two seasons, while sugars exhibited significant
      seasonal fluctuations. Upon integration of data for tomato pericarp metabolite
      profiling, factorial ANOVA identified the main factor for metabolic polymorphism
      to be the genotypic background rather than the environment or the tissue.
      Analysis of the coefficient of variance indicated greater phenotypic plasticity
      in the ILs than in the M82 tomato cultivar. Broad-sense estimate of heritability
      suggested that the mode of inheritance of metabolite traits in the seed differed
      from that in the fruit. Correlation-based metabolic network analysis comparing
      metabolite data for the seed with that for the pericarp showed that the seed
      network displayed tighter interdependence of metabolic processes than the fruit.
      Amino acids in the seed metabolic network were shown to play a central hub-like
      role in the topology of the network, maintaining high interactions with other
      metabolite categories, i.e., sugars and organic acids. Network analysis
      identified six exceptionally highly co-regulated amino acids, Gly, Ser, Thr, Ile,
      Val, and Pro. The strong interdependence of this group was confirmed by the mQTL
      mapping. Taken together these results (i) reflect the extensive redundancy of the
      regulation underlying seed metabolism, (ii) demonstrate the tight co-ordination
      of seed metabolism with respect to fruit metabolism, and (iii) emphasize the
      centrality of the amino acid module in the seed metabolic network. Finally, the
      study highlights the added value of integrating metabolic network analysis with
      mQTL mapping.

PMID- 22479207
TI  - SMG-1 and mTORC1 act antagonistically to regulate response to injury and growth
      in planarians.
AB  - Planarian flatworms are able to both regenerate their whole bodies and
      continuously adapt their size to nutrient status. Tight control of stem cell
      proliferation and differentiation during these processes is the key feature of
      planarian biology. Here we show that the planarian homolog of the
      phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR
      complex 1 components are required for this tight control. Loss of smg-1 results
      in a hyper-responsiveness to injury and growth and the formation of regenerative
      blastemas that remain undifferentiated and that lead to lethal ectopic
      outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and
      differentiation defects are hallmarks of this uncontrolled growth. These data
      imply a previously unappreciated and novel physiological function for this PIKK
      family member. In contrast we found that planarian members of the mTOR complex 1,
      tor and raptor, are required for the initial response to injury and blastema
      formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal
      growth requires mTOR signalling. We also found that the macrolide rapamycin, a
      natural compound inhibitor of mTORC1, is able to increase the survival rate of
      smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model
      where Smg-1 acts as a novel regulator of both the response to injury and growth
      control mechanisms. Our data suggest the possibility that this may be by
      suppressing mTOR signalling. Characterisation of both the planarian mTORC1
      signalling components and another PIKK family member as key regulators of
      regeneration and growth will influence future work on regeneration, growth
      control, and the development of anti-cancer therapies that target mTOR
      signalling.

PMID- 22479209
TI  - Too much cleavage of cyclin E promotes breast tumorigenesis.

PMID- 22479208
TI  - Diverse forms of RPS9 splicing are part of an evolving autoregulatory circuit.
AB  - Ribosomal proteins are essential to life. While the functions of ribosomal
      protein-encoding genes (RPGs) are highly conserved, the evolution of their
      regulatory mechanisms is remarkably dynamic. In Saccharomyces cerevisiae, RPGs
      are unusual in that they are commonly present as two highly similar gene copies
      and in that they are over-represented among intron-containing genes. To
      investigate the role of introns in the regulation of RPG expression, we
      constructed 16 S. cerevisiae strains with precise deletions of RPG introns. We
      found that several yeast introns function to repress rather than to increase
      steady-state mRNA levels. Among these, the RPS9A and RPS9B introns were required
      for cross-regulation of the two paralogous gene copies, which is consistent with
      the duplication of an autoregulatory circuit. To test for similar intron function
      in animals, we performed an experimental test and comparative analyses for
      autoregulation among distantly related animal RPS9 orthologs. Overexpression of
      an exogenous RpS9 copy in Drosophila melanogaster S2 cells induced alternative
      splicing and degradation of the endogenous copy by nonsense-mediated decay (NMD).
      Also, analysis of expressed sequence tag data from distantly related animals,
      including Homo sapiens and Ciona intestinalis, revealed diverse alternatively
      spliced RPS9 isoforms predicted to elicit NMD. We propose that multiple forms of
      splicing regulation among RPS9 orthologs from various eukaryotes operate
      analogously to translational repression of the alpha operon by S4, the distant
      prokaryotic ortholog. Thus, RPS9 orthologs appear to have independently evolved
      variations on a fundamental autoregulatory circuit.

PMID- 22479210
TI  - Genetic analysis of floral symmetry in Van Gogh's sunflowers reveals independent
      recruitment of CYCLOIDEA genes in the Asteraceae.
AB  - The genetic basis of floral symmetry is a topic of great interest because of its
      effect on pollinator behavior and, consequently, plant diversification. The
      Asteraceae, which is the largest family of flowering plants, is an ideal system
      in which to study this trait, as many species within the family exhibit a
      compound inflorescence containing both bilaterally symmetric (i.e., zygomorphic)
      and radially symmetric (i.e., actinomorphic) florets. In sunflower and related
      species, the inflorescence is composed of a single whorl of ray florets
      surrounding multiple whorls of disc florets. We show that in double-flowered
      (dbl) sunflower mutants (in which disc florets develop bilateral symmetry), such
      as those captured by Vincent van Gogh in his famous nineteenth-century sunflower
      paintings, an insertion into the promoter region of a CYCLOIDEA (CYC)-like gene
      (HaCYC2c) that is normally expressed specifically in WT rays is instead expressed
      throughout the inflorescence, presumably resulting in the observed loss of
      actinomorphy. This same gene is mutated in two independent tubular-rayed (tub)
      mutants, though these mutations involve apparently recent transposon insertions,
      resulting in little or no expression and radialization of the normally
      zygomorphic ray florets. Interestingly, a phylogenetic analysis of CYC-like genes
      from across the family suggests that different paralogs of this fascinating gene
      family have been independently recruited to specify zygomorphy in different
      species within the Asteraceae.

PMID- 22479211
TI  - Phosphorylation of the Drosophila melanogaster RNA-binding protein HOW by
      MAPK/ERK enhances its dimerization and activity.
AB  - Drosophila melanogaster Held Out Wings (HOW) is a conserved RNA-binding protein
      (RBP) belonging to the STAR family, whose closest mammalian ortholog Quaking
      (QKI) has been implicated in embryonic development and nervous system
      myelination. The HOW RBP modulates a variety of developmental processes by
      controlling mRNA levels and the splicing profile of multiple key regulatory
      genes; however, mechanisms regulating its activity in tissues have yet to be
      elucidated. Here, we link receptor tyrosine kinase (RTK) signaling to the
      regulation of QKI subfamily of STAR proteins, by showing that HOW undergoes
      phosphorylation by MAPK/ERK. Importantly, we show that this modification
      facilitates HOW dimerization and potentiates its ability to bind RNA and regulate
      its levels. Employing an antibody that specifically recognizes phosphorylated
      HOW, we show that HOW is phosphorylated in embryonic muscles and heart
      cardioblasts in vivo, thus documenting for the first time Serine/Threonine
      (Ser/Thr) phosphorylation of a STAR protein in the context of an intact organism.
      We also identify the sallimus/D-titin (sls) gene as a novel muscle target of HOW
      mediated negative regulation and further show that this regulation is
      phosphorylation-dependent, underscoring the physiological relevance of this
      modification. Importantly, we demonstrate that HOW Thr phosphorylation is reduced
      following muscle-specific knock down of Drosophila MAPK rolled and that,
      correspondingly, Sls is elevated in these muscles, similarly to the HOW RNAi
      effect. Taken together, our results provide a coherent mechanism of differential
      HOW activation; MAPK/ERK-dependent phosphorylation of HOW promotes the formation
      of HOW dimers and thus enhances its activity in controlling mRNA levels of key
      muscle-specific genes. Hence, our findings bridge between MAPK/ERK signaling and
      RNA regulation in developing muscles.

PMID- 22479212
TI  - DNA resection at chromosome breaks promotes genome stability by constraining non
      allelic homologous recombination.
AB  - DNA double-strand breaks impact genome stability by triggering many of the large
      scale genome rearrangements associated with evolution and cancer. One of the
      first steps in repairing this damage is 5'->3' resection beginning at the break
      site. Recently, tools have become available to study the consequences of not
      extensively resecting double-strand breaks. Here we examine the role of Sgs1- and
      Exo1-dependent resection on genome stability using a non-selective assay that we
      previously developed using diploid yeast. We find that Saccharomyces cerevisiae
      lacking Sgs1 and Exo1 retains a very efficient repair process that is highly
      mutagenic to genome structure. Specifically, 51% of cells lacking Sgs1 and Exo1
      repair a double-strand break using repetitive sequences 12-48 kb distal from the
      initial break site, thereby generating a genome rearrangement. These Sgs1- and
      Exo1-independent rearrangements depend partially upon a Rad51-mediated homologous
      recombination pathway. Furthermore, without resection a robust cell cycle arrest
      is not activated, allowing a cell with a single double-strand break to divide
      before repair, potentially yielding multiple progeny each with a different
      rearrangement. This profusion of rearranged genomes suggests that cells tolerate
      any dangers associated with extensive resection to inhibit mutagenic pathways
      such as break-distal recombination. The activation of break-distal recipient
      repeats and amplification of broken chromosomes when resection is limited raise
      the possibility that genome regions that are difficult to resect may be hotspots
      for rearrangements. These results may also explain why mutations in resection
      machinery are associated with cancer.

PMID- 22479214
TI  - We're Not in Kansas Anymore.

PMID- 22479202
TI  - Novel loci for adiponectin levels and their influence on type 2 diabetes and
      metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
AB  - Circulating levels of adiponectin, a hormone produced predominantly by
      adipocytes, are highly heritable and are inversely associated with type 2
      diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis
      of genome-wide association studies in 39,883 individuals of European ancestry to
      identify genes associated with metabolic disease. We identified 8 novel loci
      associated with adiponectin levels and confirmed 2 previously reported loci (P =
      4.5*10(-8)-1.2*10(-43)). Using a novel method to combine data across ethnicities
      (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we
      identified two additional novel loci. Expression analyses of 436 human adipocyte
      samples revealed that mRNA levels of 18 genes at candidate regions were
      associated with adiponectin concentrations after accounting for multiple testing
      (p<3*10(-4)). We next developed a multi-SNP genotypic risk score to test the
      association of adiponectin decreasing risk alleles on metabolic traits and
      diseases using consortia-level meta-analytic data. This risk score was associated
      with increased risk of T2D (p = 4.3*10(-3), n = 22,044), increased triglycerides
      (p = 2.6*10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8*10(-5), n =
      77,167), increased glucose two hours post oral glucose tolerance testing (p =
      4.4*10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but
      with lower in HDL-cholesterol concentrations (p = 4.5*10(-13), n = 96,748) and
      decreased BMI (p = 1.4*10(-4), n = 121,335). These findings identify novel
      genetic determinants of adiponectin levels, which, taken together, influence risk
      of T2D and markers of insulin resistance.

PMID- 22479215
TI  - Needed: a new business model.

PMID- 22479213
TI  - Heritability and genetic correlations explained by common SNPs for metabolic
      syndrome traits.
AB  - We used a bivariate (multivariate) linear mixed-effects model to estimate the
      narrow-sense heritability (h(2)) and heritability explained by the common SNPs
      (h(g)(2)) for several metabolic syndrome (MetS) traits and the genetic
      correlation between pairs of traits for the Atherosclerosis Risk in Communities
      (ARIC) genome-wide association study (GWAS) population. MetS traits included body
      mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP),
      fasting glucose (GLU), fasting insulin (INS), fasting trigylcerides (TG), and
      fasting high-density lipoprotein (HDL). We found the percentage of h(2) accounted
      for by common SNPs to be 58% of h(2) for height, 41% for BMI, 46% for WHR, 30%
      for GLU, 39% for INS, 34% for TG, 25% for HDL, and 80% for SBP. We confirmed
      prior reports for height and BMI using the ARIC population and independently in
      the Framingham Heart Study (FHS) population. We demonstrated that the
      multivariate model supported large genetic correlations between BMI and WHR and
      between TG and HDL. We also showed that the genetic correlations between the MetS
      traits are directly proportional to the phenotypic correlations.

PMID- 22479217
TI  - Everyone wants in, but with no ground rules, the biosimilar business remains
      elusive.

PMID- 22479218
TI  - Setting the Bar Higher For Off-Label Use of Biologics: Off-label use of biologics
      is common as physicians strive for optimal treatment. Patients want whatever
      works. Drug makers want expanded labeling, but payers chafe at the lack of
      efficacy data. Is there an answer to this conundrum?
AB  - Off-label use of biologics is common as physicians strive to treat patients as
      best they can. But payers and purchasers want evidence of value before they pay
      for off-label use, and the FDA has moved to mitigate off-label prescribing. With
      patient activism increasing, how should off-label use be handled? And where do
      the drug makers fit in?

PMID- 22479219
TI  - A Conversation With Scott Gottlieb, MD: The impact of health care reform on
      access to biologics, health policy, and managed care.
AB  - The former CMS and FDA insider talks about the many challenges that plague the
      financing of healthcare and what is needed to get affordable patient care on
      track.

PMID- 22479216
TI  - Clinical trials, research, and FDA findings.

PMID- 22479220
TI  - The biologic finance and access council 2nd annual biologics healthcare survey:
      views from key healthcare stakeholders, part 2.
AB  - Part 2 of BFAC's survey reveals a range of understanding among providers,
      purchasers, and payers about the management of biologics and the implications of
      their use.

PMID- 22479221
TI  - Managing Viral Hepatitis C: HCV: New Opportunities, High CostTwo new biologics
      establish a higher standard of care. Managing these agents, however, will be
      highly complex.
AB  - Two new biologics for HCV present treatment and cost-management challenges.

PMID- 22479222
TI  - Pitting the FDA Against CMS: The good, the bad, and the ugly about "parallel
      review.".
AB  - The good, the bad, and the ugly about the FDA/CMS parallel review process. Can it
      work?

PMID- 22479224
TI  - Breast and ovarian cancers drive drug development.

PMID- 22479223
TI  - Therapeutic vaccine for brain cancer succeeds using a unique approach.

PMID- 22479225
TI  - The business of biologics.

PMID- 22479227
TI  - Talking to Different Audiences: Mini-Sentinel, precursor to the FDA's long
      awaited Sentinel drug safety surveillance system, may soon reap benefits for
      insurers and patients.

PMID- 22479226
TI  - Clinical trials, research, and FDA findings.

PMID- 22479228
TI  - How Will Biologics Fit Into Healthcare Reform?: With so many variables, it's hard
      to predict what kind of market will exist for biologics and other specialty drugs
      in 2014. Current trends may provide some insight.
AB  - The Institute of Medicine says that health benefit packages should be limited by
      cost, not services, but doesn't address the coverage of biologics. Employers,
      meanwhile, are thinking about limiting access to high-priced drugs. Yet, industry
      reports say that biologics are set to dominate drug spend by 2015. Are we moving
      toward healthcare rationing?

PMID- 22479229
TI  - Renewing Humans: Regenerative medicine is set for explosive growth. Proponents
      believe that some of the advances in this field will evolve into therapeutic
      practices that will forever change healthcare.
AB  - Some pioneers in this burgeoning field say that regenerative therapies will
      forever change healthcare and provide a fourfold return on investment. Hope? Or
      hype?

PMID- 22479230
TI  - Employers Struggle To Cope With the Rising Use of Biologics: Tradeoffs in cost
      sharing or higher deductibles could derail treatment and decrease the value of
      healthcare spending.
AB  - Employers have tried everything from uptiering to tighter utilization management
      in trying to mitigate the high cost of biologics. They now hope that biosimilars
      may offer some relief. But there's another option - one they should take a hard
      look at.

PMID- 22479231
TI  - New approaches to treat cancer - what they can and cannot do.
AB  - Delivering drugs directly to tumors and overcoming drug resistance are two
      hurdles that face cancer researchers. Here's a look at where cancer treatment
      stands.

PMID- 22479232
TI  - Gene Patent Reform: Still in Doubt: The patent-eligibility doctrine remains in
      limbo as the battle over gene patents cuts a tortuous path through the court
      system.

PMID- 22479233
TI  - Leahy-Smith Act Sets a New Foundation: The new patent law puts the U.S. in line
      with the rest of the world and gives biotechs an edge they have long wanted.

PMID- 22479234
TI  - New Automated HER2 Test Promises Faster, More Accurate Testing.

PMID- 22479235
TI  - The role of information communication technology (ICT) towards universal health
      coverage: the first steps of a telemedicine project in Ethiopia.
AB  - BACKGROUND: Eighty-five per cent of the Ethiopian population lives in remote
      areas, without access to modern health services. The limited health care budget,
      chronic shortage of health care workers and lack of incentives to retain those in
      remote areas further jeopardize the national health care delivery system.
      Recently, the application of information communication technology (ICT) to health
      care delivery and the use of telemedicine have raised hopes. OBJECTIVE: This
      paper analyzes the challenges, failures and successes encountered in setting-up
      and implementing a telemedicine program in Ethiopia and provides possible
      recommendations for developing telemedicine strategies in countries with limited
      resources. DESIGN: Ten sites in Ethiopia were selected to participate in this
      pilot between 2004 and 2006 and twenty physicians, two per site, were trained in
      the use of a store and forward telemedicine system, using a dial-up internet
      connection. Teledermatology, teleradiology and telepathology were the chosen
      disciplines for the electronic referrals, across the selected ten sites. RESULTS:
      Telemedicine implementation does not depend only on technological factors, rather
      on e-government readiness, enabling policies, multisectoral involvement and
      capacity building processes. There is no perfect 'one size fits all' technology
      and the use of combined interoperable applications, according to the local
      context, is highly recommended. CONCLUSIONS: Telemedicine is still in a premature
      phase of development in Ethiopia and other sub-Saharan African countries, and it
      remains difficult to talk objectively about measurable impact of its use, even
      though it has demonstrated practical applicability beyond reasonable doubts.

PMID- 22479236
TI  - Filter Bank Common Spatial Pattern Algorithm on BCI Competition IV Datasets 2a
      and 2b.
AB  - The Common Spatial Pattern (CSP) algorithm is an effective and popular method for
      classifying 2-class motor imagery electroencephalogram (EEG) data, but its
      effectiveness depends on the subject-specific frequency band. This paper presents
      the Filter Bank Common Spatial Pattern (FBCSP) algorithm to optimize the subject
      specific frequency band for CSP on Datasets 2a and 2b of the Brain-Computer
      Interface (BCI) Competition IV. Dataset 2a comprised 4 classes of 22 channels EEG
      data from 9 subjects, and Dataset 2b comprised 2 classes of 3 bipolar channels
      EEG data from 9 subjects. Multi-class extensions to FBCSP are also presented to
      handle the 4-class EEG data in Dataset 2a, namely, Divide-and-Conquer (DC), Pair
      Wise (PW), and One-Versus-Rest (OVR) approaches. Two feature selection algorithms
      are also presented to select discriminative CSP features on Dataset 2b, namely,
      the Mutual Information-based Best Individual Feature (MIBIF) algorithm, and the
      Mutual Information-based Rough Set Reduction (MIRSR) algorithm. The single-trial
      classification accuracies were presented using 10 * 10-fold cross-validations on
      the training data and session-to-session transfer on the evaluation data from
      both datasets. Disclosure of the test data labels after the BCI Competition IV
      showed that the FBCSP algorithm performed relatively the best among the other
      submitted algorithms and yielded a mean kappa value of 0.569 and 0.600 across all
      subjects in Datasets 2a and 2b respectively.

PMID- 22479237
TI  - Head direction maps remain stable despite grid map fragmentation.
AB  - Areas encoding space in the brain contain both representations of position (place
      cells and grid cells) and representations of azimuth (head direction cells).
      Previous studies have already suggested that although grid cells and head
      direction cells reside in the same brain areas, the calculation of head direction
      is not dependent on the calculation of position. Here we demonstrate that
      realignment of grid cells does not affect head direction tuning. We analyzed head
      direction cell data collected while rats performed a foraging task in a multi
      compartment environment (the hairpin maze) vs. an open-field environment,
      demonstrating that the tuning of head direction cells did not change when the
      environment was divided into multiple sub-compartments, in the hairpin maze. On
      the other hand, as we have shown previously (Derdikman et al., 2009), the
      hexagonal firing pattern expressed by grid cells in the open-field broke down
      into repeating patterns in similar alleys when rats traversed the multi
      compartment hairpin maze. The grid-like firing of conjunctive cells, which
      express both grid properties and head direction properties in the open-field,
      showed a selective fragmentation of grid-like firing properties in the hairpin
      maze, while the head directionality property of the same cells remained
      unaltered. These findings demonstrate that head direction is not affected during
      the restructuring of grid cell firing fields as a rat actively moves between
      compartments, thus strengthening the claim that the head direction system is
      upstream from or parallel to the grid-place system.

PMID- 22479238
TI  - Tinnitus suppression by electric stimulation of the auditory nerve.
AB  - Electric stimulation of the auditory nerve via a cochlear implant (CI) has been
      observed to suppress tinnitus, but parameters of an effective electric stimulus
      remain unexplored. Here we used CI research processors to systematically vary
      pulse rate, electrode place, and current amplitude of electric stimuli, and
      measure their effects on tinnitus loudness and stimulus loudness as a function of
      stimulus duration. Thirteen tinnitus subjects who used CIs were tested, with nine
      (70%) being "Responders" who achieved greater than 30% tinnitus loudness
      reduction in response to at least one stimulation condition and the remaining
      four (30%) being "Non-Responders" who had less than 30% tinnitus loudness
      reduction in response to any stimulus condition tested. Despite large individual
      variability, several interesting observations were made between stimulation
      parameters, tinnitus characteristics, and tinnitus suppression. If a subject's
      tinnitus was suppressed by one stimulus, then it was more likely to be suppressed
      by another stimulus. If the tinnitus contained a "pulsating" component, then it
      would be more likely suppressed by a given combination of stimulus parameters
      than tinnitus without these components. There was also a disassociation between
      the subjects' clinical speech processor and our research processor in terms of
      their effectiveness in tinnitus suppression. Finally, an interesting dichotomy
      was observed between loudness adaptation to electric stimuli and their effects on
      tinnitus loudness, with the Responders exhibiting higher degrees of loudness
      adaptation than the Non-Responders. Although the mechanisms underlying these
      observations remain to be resolved, their clinical implications are clear. When
      using a CI to manage tinnitus, the clinical processor that is optimized for
      speech perception needs to be customized for optimal tinnitus suppression.

PMID- 22479239
TI  - Fragmentation: loss of global coherence or breakdown of modularity in functional
      brain architecture?
AB  - Psychiatric illnesses characterized by disorganized cognition, such as
      schizophrenia, have been described in terms of fragmentation and hence understood
      as reduction in functional brain connectivity, particularly in prefrontal and
      parietal areas. However, as graph theory shows, relatively small numbers of
      nonlocal connections are sufficient to ensure global coherence in the modular
      small-world network structure of the brain. We reconsider fragmentation in this
      perspective. Computational studies have shown that for a given level of
      connectivity in a model of coupled nonlinear oscillators, modular small-world
      networks evolve from an initially random organization. Here we demonstrate that
      with decreasing connectivity, the probability of evolving into a modular small
      world network breaks down at a critical point, which scales to the percolation
      function of random networks with a universal exponent of alpha = 1.17. Thus,
      according to the model, local modularity systematically breaks down before there
      is loss of global coherence in network connectivity. We, therefore, propose that
      fragmentation may involve, at least in its initial stages, the inability of a
      dynamically evolving network to sustain a modular small-world structure. The
      result is in a shift in the balance in schizophrenia from local to global
      functional connectivity.

PMID- 22479240
TI  - Interval timing and time-based decision making.

PMID- 22479242
TI  - Neuroeconomics.

PMID- 22479241
TI  - Toward a limbic cortical inhibitory network: implications for hypothalamic
      pituitary-adrenal responses following chronic stress.
AB  - A network of interconnected cell groups in the limbic forebrain regulates
      hypothalamic-pituitary-adrenal (HPA) axis activation during emotionally stressful
      experiences, and disruption of these systems is broadly implicated in the onset
      of psychiatric illnesses. A significant challenge has been to unravel the
      circuitry and mechanisms providing for regulation of HPA output, as these limbic
      forebrain regions do not provide any direct innervation of HPA effector cell
      groups in the paraventricular hypothalamus (PVH). Recent evidence will be
      highlighted that endorses a discrete region within the bed nuclei of the stria
      terminalis serving as a neural hub for integrating and relaying HPA-inhibitory
      influences to the PVH during emotional stress, whereas the prevailing view has
      involved a more complex organization of mulitple cell groups arranged in parallel
      between the forebrain and PVH. A hypothesis will be advanced that accounts for
      the capacity of this network to constrain the magnitude and/or duration of HPA
      axis output in response to emotionally stressful experiences, and for how chronic
      stress-induced synaptic reorganization in key cell groups may lead to an
      attrition of these influences, resulting in HPA axis hyperactivity.

PMID- 22479243
TI  - The effect of leisure activity golf practice on motor imagery: an fMRI study in
      middle adulthood.
AB  - Much is known about practice-induced plasticity of the motor system. But it is
      not clear how a physical training influences the mental rehearsal of the
      practiced task and its associated hemodynamic responses. In the present
      longitudinal study with two measurement time-points, we used the method of
      functional magnetic resonance imaging (fMRI) and a motor imagery task, in order
      to explore the dynamic neuro-functional changes induced by a highly complex
      physical training. The 11 golf novices between the age of 40 and 60 years
      practiced the motor training as leisure activity. Additionally, data from an age
      and sex-matched control group without golf training was collected. As a main
      result, we demonstrate that changes between the two measurement time-points were
      only found in the golf novice group. The golf novices showed a decrease in
      hemodynamic responses during the mental rehearsal of the golf swing in non
      primary motor areas after the 40 h of golf practice. Thus, the results indicate
      that a complex physical leisure activity induces functional neuroplasticity in
      the seldom studied population of middle-aged adults, and that this effect is
      evident during mental rehearsal of the practiced task. This finding supports the
      idea that (a) a skill improvement is associated with a modified activation
      pattern in the associated neuronal network that can be identified during mental
      rehearsal of the practiced task, and that (b) a strict training protocol is not
      necessary to induce functional neuroplasticity.

PMID- 22479244
TI  - Losing the battle but winning the war: game theoretic analysis of the competition
      between motoneurons innervating a skeletal muscle.
AB  - The fibers in a skeletal muscle are divided into groups called "muscle units"
      whereby each muscle unit is innervated by a single neuron. It was found that
      neurons with low activation thresholds have smaller muscle units than neurons
      with higher activation thresholds. This results in a fixed recruitment order of
      muscle units, from smallest to largest, called the "size principle." It is
      thought that the size principle results from a competitive process-taking place
      after birth-between the neurons innervating the muscle. The underlying mechanism
      of the competition was not understood. Moreover, the results in the majority of
      experiments that manipulated the activity during the competition period seemed to
      contradict the size principle. Experiments at the isolated muscle fibers showed
      that the competition is governed by a Hebbian-like rule, whereby neurons with low
      activation thresholds have a competitive advantage at any single muscle fiber.
      Thus neurons with low activation thresholds are expected to have larger muscle
      units in contradiction to what is seen empirically. This state of affairs was
      termed "paradoxical." In the present study we developed a new game theoretic
      framework to analyze such competitive biological processes. In this game, neurons
      are the players competing to innervate a maximal number of muscle fibers. We
      showed that in order to innervate more muscle fibers, it is advantageous to win
      (as the neurons with higher activation thresholds do) later competitions. This
      both explains the size principle and resolves the seemingly paradoxical
      experimental data. Our model establishes that the competition at each muscle
      fiber may indeed be Hebbian and that the size principle still emerges from these
      competitions as an overall property of the system. Thus, the less active neurons
      "lose the battle but win the war." Our model provides experimentally testable
      predictions. The new game-theoretic approach may be applied to competitions in
      other biological systems.

PMID- 22479245
TI  - Does emotional memory enhancement assist the memory-impaired?
AB  - We review recent work on emotional memory enhancement in older adults and
      patients with mild cognitive impairment (MCI) or Alzheimer dementia (AD) and
      evaluate the viability of incorporating emotional components into cognitive
      rehabilitation for these groups. First, we identify converging evidence regarding
      the effects of emotional valence on working memory in healthy aging. Second, we
      introduce work that suggests a more complex role for emotional memory enhancement
      in aging and identify a model capable of unifying disparate research findings.
      Third, we survey the neuroimaging literature for evidence of a special role for
      the amygdala in MCI and early AD in emotional memory enhancement. Finally, we
      assess the theoretical feasibility of incorporating emotional content into
      cognitive rehabilitation given all available evidence.

PMID- 22479247
TI  - Sodium channels as targets for volatile anesthetics.
AB  - The molecular mechanisms of modern inhaled anesthetics are still poorly
      understood although they are widely used in clinical settings. Considerable
      evidence supports effects on membrane proteins including ligand- and voltage
      gated ion channels of excitable cells. Na(+) channels are crucial to action
      potential initiation and propagation, and represent potential targets for
      volatile anesthetic effects on central nervous system depression. Inhibition of
      presynaptic Na(+) channels leads to reduced neurotransmitter release at the
      synapse and could therefore contribute to the mechanisms by which volatile
      anesthetics produce their characteristic end points: amnesia, unconsciousness,
      and immobility. Early studies on crayfish and squid giant axon showed inhibition
      of Na(+) currents by volatile anesthetics at high concentrations. Subsequent
      studies using native neuronal preparations and heterologous expression systems
      with various mammalian Na(+) channel isoforms implicated inhibition of
      presynaptic Na(+) channels in anesthetic actions at clinical concentrations.
      Volatile anesthetics reduce peak Na(+) current (I(Na)) and shift the voltage of
      half-maximal steady-state inactivation (h(infinity)) toward more negative
      potentials, thus stabilizing the fast-inactivated state. Furthermore recovery
      from fast-inactivation is slowed, together with enhanced use-dependent block
      during pulse train protocols. These effects can depress presynaptic excitability,
      depolarization and Ca(2+) entry, and ultimately reduce transmitter release. This
      reduction in transmitter release is more potent for glutamatergic compared to
      GABAergic terminals. Involvement of Na(+) channel inhibition in mediating the
      immobility caused by volatile anesthetics has been demonstrated in animal
      studies, in which intrathecal infusion of the Na(+) channel blocker tetrodotoxin
      increases volatile anesthetic potency, whereas infusion of the Na(+) channels
      agonist veratridine reduces anesthetic potency. These studies indicate that
      inhibition of presynaptic Na(+) channels by volatile anesthetics is involved in
      mediating some of their effects.

PMID- 22479246
TI  - Barrier mechanisms in the developing brain.
AB  - The adult brain functions within a well-controlled stable environment, the
      properties of which are determined by cellular exchange mechanisms superimposed
      on the diffusion restraint provided by tight junctions at interfaces between
      blood, brain and cerebrospinal fluid (CSF). These interfaces are referred to as
      "the" blood-brain barrier. It is widely believed that in embryos and newborns,
      this barrier is immature or "leaky," rendering the developing brain more
      vulnerable to drugs or toxins entering the fetal circulation from the mother. New
      evidence shows that many adult mechanisms, including functionally effective tight
      junctions are present in embryonic brain and some transporters are more active
      during development than in the adult. Additionally, some mechanisms present in
      embryos are not present in adults, e.g., specific transport of plasma proteins
      across the blood-CSF barrier and embryo-specific intercellular junctions between
      neuroependymal cells lining the ventricles. However developing cerebral vessels
      appear to be more fragile than in the adult. Together these properties may render
      developing brains more vulnerable to drugs, toxins, and pathological conditions,
      contributing to cerebral damage and later neurological disorders. In addition,
      after birth loss of protection by efflux transporters in placenta may also render
      the neonatal brain more vulnerable than in the fetus.

PMID- 22479248
TI  - The validation of a functional, isolated pig bladder model for physiological
      experimentation.
AB  - Characterizing the integrative physiology of the bladder requires whole organ
      preparations. The purpose of this study was to validate an isolated large animal
      (pig) bladder preparation, through arterial and intravesical drug administration,
      intravesical pressure recording, and filming of surface micromotions. Female pig
      bladders were obtained from the local abattoir and arterially perfused in vitro.
      Arterial and intravesical pressures were recorded at varying volumes. Bladder
      viability was assessed histologically and by monitoring inflow and outflow pH.
      Arterial drug administration employed boluses introduced into the perfusate.
      Intravesical administration involved slow instillation and a prolonged dwell
      time. Surface micromotions were recorded by filming the separation of surface
      markers concurrently with intravesical pressure measurement. Adequate perfusion
      to all bladder layers was achieved for up to 8 h; there was no structural
      deterioration nor alteration in inflow and effluent perfusate pH. Arterial drug
      administration (carbachol and potassium chloride) showed consistent dose
      dependent responses. Localized movements (micromotions) occurred over the bladder
      surface, with variable correlation with fluctuations of intravesical pressure.
      The isolated pig bladder is a valid approach to study integrative bladder
      physiology. It remains viable when perfused in vitro, responds to different
      routes of drug administration and provides a model to correlate movements of the
      bladder wall directly to variation of intravesical pressure.

PMID- 22479249
TI  - Whole genome amplification of DNA for genotyping pharmacogenetics candidate
      genes.
AB  - Whole genome amplification (WGA) technologies can be used to amplify genomic DNA
      when only small amounts of DNA are available. The Multiple Displacement
      Amplification Phi polymerase based amplification has been shown to accurately
      amplify DNA for a variety of genotyping assays; however, it has not been tested
      for genotyping many of the clinically relevant genes important for
      pharmacogenetic studies, such as the cytochrome P450 genes, that are typically
      difficult to genotype due to multiple pseudogenes, copy number variations, and
      high similarity to other related genes. We evaluated whole genome amplified
      samples for Taqman(TM) genotyping of SNPs in a variety of pharmacogenetic genes.
      In 24 DNA samples from the Coriell human diversity panel, the call rates, and
      concordance between amplified (~200-fold amplification) and unamplified samples
      was 100% for two SNPs in CYP2D6 and one in ESR1. In samples from a breast cancer
      clinical trial (Trial 1), we compared the genotyping results in samples before
      and after WGA for three SNPs in CYP2D6, one SNP in CYP2C19, one SNP in CYP19A1,
      two SNPs in ESR1, and two SNPs in ESR2. The concordance rates were all >97%.
      Finally, we compared the allele frequencies of 143 SNPs determined in Trial 1
      (whole genome amplified DNA) to the allele frequencies determined in unamplified
      DNA samples from a separate trial (Trial 2) that enrolled a similar population.
      The call rates and allele frequencies between the two trials were 98 and 99.7%,
      respectively. We conclude that the whole genome amplified DNA is suitable for
      Taqman(TM) genotyping for a wide variety of pharmacogenetically relevant SNPs.

PMID- 22479250
TI  - Microvesicles: novel biomarkers for neurological disorders.
AB  - Microvesicles (MVs) are released by most cell types in physiological conditions,
      but their number is often increased upon cellular activation or neoplastic
      transformation. This suggests that their detection may be helpful in pathological
      conditions to have information on activated cell types and, possibly, on the
      nature of the activation. This could be of paramount importance in districts and
      tissues that are not accessible to direct examination, such as the central
      nervous system. Increased release of MVs has been described to be associated to
      the acute or active phase of several neurological disorders. While the
      subcellular origin of MVs (exosome or ectosomes) is basically never addressed in
      these studies because of technical limitations, the cell of origin is always
      identified. Endothelium- or platelet-derived MVs, detected in plasma or serum,
      are linked to neurological pathologies with a vascular or ischemic pathogenic
      component, and may represent a very useful marker to support therapeutic choices
      in stroke. In neuroinflammatory disorders, such as multiple sclerosis, MVs of
      oligodendroglial, or microglial origin have been described in the cerebrospinal
      fluid and may carry, in perspective, additional information on the biological
      alterations in their cell of origin. Little specific evidence is available in
      neurodegenerative disorders and, specifically, MVs of neural origin have never
      been investigated in these pathologies. Few data have been reported for
      neuroinfection and brain trauma. In brain tumors, despite the limited number of
      studies performed, results are very promising and potentially close to clinical
      translation. We here review all currently available data on the detection of MVs
      in neurological diseases, limiting our search to exclusively human studies.
      Current literature and our own data indicate that MVs detection may represent a
      very promising strategy to gain pathogenic information, identify therapeutic
      targets, and select specific biomarkers for neurological disorders.

PMID- 22479252
TI  - Eventual role of asymptomatic cases of dengue for the introduction and spread of
      dengue viruses in non-endemic regions.
AB  - In dengue virus infections the asymptomatic cases are much more frequent than the
      symptomatic ones, but their true role in the introduction and subsequent spread
      of dengue viruses in non-endemic regions remains to de clarified. We analyzed
      data from English and French literatures to assess if viremia in asymptomatic
      dengue infections might be sufficient to represent a true risk. During outbreaks
      of dengue a large number of individuals are infected and since viremia levels in
      symptomatic patients are known to vary by many orders of magnitude, it is
      reasonable to augur that a proportion of asymptomatic cases might reach levels of
      viremia sufficient to infect competent mosquitoes. In addition, a number of new
      ways of contamination in man by dengue viruses were recently described such as
      blood transfusion, bone marrow transplantation, and nosocomial infections that
      may be worth considering.

PMID- 22479251
TI  - MicroRNA Regulation of SIRT1.
AB  - SIRT1 is an NAD-dependent deacetylase that regulates stress response pathways. By
      deacetylating transcription factors and co-factors, SIRT1 modulates metabolism,
      inflammation, hypoxic responses, circadian rhythms, cell survival, and longevity.
      Since SIRT1 plays a key role in regulating pathways involved in cardiovascular
      diseases and metabolic diseases cancer, the regulation of SIRT1 has received
      intense scrutiny. The post-transcriptional regulation of SIRT1 is mediated by two
      classes of molecules, RNA-binding proteins (RBPs) and non-coding small RNAs.
      MicroRNAs (miRNAs) are short non-coding RNAs that regulate target gene expression
      in a post-transcriptional manner. More than 16 miRNAs modulate SIRT1 expression,
      including miR-34a. miR-34a induces colon cancer apoptosis through SIRT1, and miR
      34a also promotes senescence in endothelial cells via SIRT1. This review
      describes the impact of miRNAs on SIRT1. The background of SIRT1 and miRNAs will
      be summarized, followed by the mechanism by which several key miRNAs alter SIRT1
      levels, and how the RBP HuR regulates SIRT1. MicroRNA regulation of SIRT1 might
      affect a wide variety of pathways in humans, from metabolic diseases such as
      diabetes to cardiovascular diseases and cancer.

PMID- 22479253
TI  - Linking global warming, metabolic rate of hematophagous vectors, and the
      transmission of infectious diseases.

PMID- 22479254
TI  - CD-1 mice Show Individual Differences in Nicotine Preference in a Modified Two
      Bottle Oral Self-Administration Model.
AB  - Although both animal and human studies reveal significant contributions of
      genetics to smoking addiction, many human studies were underpowered or biased by
      potential confounding variables, and animal genetic studies are challenged by
      limited genetic variations and lack of convincing phenotypes. To address these
      concerns, we used non-sibling outbred CD-1 mice to evaluate individual
      differences in nicotine preference with a modified two-bottle oral self
      administration model. Animals were first given free access to two bottles, one
      filled with nicotine dissolved in 2% saccharin and the other with saccharin only.
      Under this regular two-bottle choice condition, the majority of animals avoided
      the nicotine solution with limited individual differences. However, when we
      modified the model by introducing 4 days of exposure to 5% saccharin in the
      drinking water, the animals significantly increased nicotine consumption in the
      two-bottle choice test, with about 30% animals showing a nicotine preference.
      Nicotine preference after 5% saccharin treatment remained elevated throughout the
      28 days of the experiment. Further, we found there existed striking individual
      differences in nicotine consumption after exposure to 5% saccharin, with a range
      of 0-100% of total liquid consumption. The enhanced individual differences and
      the ratio of nicotine consumption were observed at different concentrations of
      nicotine (10-80 MUg/ml) and in both adolescents and adults. Further examination
      on the induction mechanism showed that the long-lasting nicotine preference was
      not correlated with nicotine consumption before the induction, 5% saccharin
      consumption, or weight gain during the induction. Although liquid consumption
      during the 4 days of 5% saccharin exposure was decreased by about 30%, comparable
      liquid restriction alone for 4 days did not induce nicotine preference. Together,
      this study showed a strong and stable nicotine preference in CD-1 mice, which was
      induced by a short-term high concentration of saccharin in the drinking water.
      Considering the nature and heterogeneity of CD-1 mice, the striking individual
      differences imply that genetics plays an important role in nicotine preference
      observed in these animals.

PMID- 22479256
TI  - Perceptual learning and feature-based approaches to concepts - a critical
      discussion.
AB  - A central challenge for any theory of concept learning comes from Fodor's
      argument against the learning of concepts, which lies at the basis of
      contemporary computationalist accounts of the mind. Robert Goldstone and his
      colleagues propose a theory of perceptual learning that attempts to overcome
      Fodor's challenge. Its main component is the addition of a cognitive device at
      the interface of perception and conception, which slowly builds "cognitive
      symbols" out of perceptual stimuli. Two main mechanisms of concept creation are
      unitization and differentiation. In this paper, I will present and examine their
      theory, and will show that two problems hinder this reply to Fodor's challenge
      from being a successful answer to the challenge. To amend the theory, I will
      argue that one would need to say more about the input systems to unitization and
      differentiation, and be clearer on the representational format that they are able
      to operate upon. Until these issues have been addressed, the proposal does not
      deploy its full potential to threaten a Fodorian position.

PMID- 22479255
TI  - Color improves speed of processing but not perception in a motion illusion.
AB  - When two superimposed surfaces of dots move in different directions, the
      perceived directions are shifted away from each other. This perceptual illusion
      has been termed direction repulsion and is thought to be due to mutual inhibition
      between the representations of the two directions. It has further been shown that
      a speed difference between the two surfaces attenuates direction repulsion. As
      speed and direction are both necessary components of representing motion, the
      reduction in direction repulsion can be attributed to the additional motion
      information strengthening the representations of the two directions and thus
      reducing the mutual inhibition. We tested whether bottom-up attention and top
      down task demands, in the form of color differences between the two surfaces,
      would also enhance motion processing, reducing direction repulsion. We found that
      the addition of color differences did not improve direction discrimination and
      reduce direction repulsion. However, we did find that adding a color difference
      improved performance on the task. We hypothesized that the performance
      differences were due to the limited presentation time of the stimuli. We tested
      this in a follow-up experiment where we varied the time of presentation to
      determine the duration needed to successfully perform the task with and without
      the color difference. As we expected, color segmentation reduced the amount of
      time needed to process and encode both directions of motion. Thus we find a
      dissociation between the effects of attention on the speed of processing and
      conscious perception of direction. We propose four potential mechanisms wherein
      color speeds figure-ground segmentation of an object, attentional switching
      between objects, direction discrimination and/or the accumulation of motion
      information for decision-making, without affecting conscious perception of the
      direction. Potential neural bases are also explored.

PMID- 22479257
TI  - Cerebral asymmetry in insomnia sufferers.
AB  - Cerebral asymmetry is used to describe the differences in electroencephalographic
      activity between regions of the brain. The objective of this study was to
      document frontal, central, and parietal asymmetry in psychophysiological (Psy-I)
      and paradoxical (Para-I) insomnia sufferers as well as good sleeper (GS)
      controls, and to compare their patterns of asymmetry to others already found in
      anxiety and depression. Additionally, asymmetry variations between nights were
      assessed. Participants were 17 Psy-I, 14 Para-I, and 19 GS (mean age = 40 years,
      SD = 9.4). They completed three nights of polysomnography (PSG) recordings
      following a clinical evaluation in a sleep laboratory. All sleep cycles of Nights
      2 and 3 were retained for power spectral analysis. The absolute activity in
      frequency bands (0.00-125.00 Hz) was computed at multiple frontal, central, and
      parietal sites in rapid eye movement and non-rapid eye movement sleep to provide
      cerebral asymmetry measures. Mixed model ANOVAs were computed to assess
      differences between groups and nights. Correlations were performed with asymmetry
      and symptoms of depression and anxiety from self-reported questionnaires. Over
      the course of the two nights, Para-I tended to present hypoactivation of their
      left frontal region but hyperactivation of their right one compared with GS. As
      for Psy-I, they presented increased activation of their right parietal region
      compared with Para-I. Asymmetry at frontal, central, and parietal region differed
      between nights. On a more disrupted night of sleep, Psy-I had increased activity
      in their right parietal region while Para-I presented a decrease in cerebral
      activity in the right central region on their less disrupted night of sleep.
      Anxious and depressive symptoms did not correlate with asymmetry at any region.
      Therefore, Psy-I and Para-I present unique patterns of cerebral asymmetry that do
      not relate to depression or anxiety, and asymmetry varies between nights, maybe
      as a consequence of variability in objective sleep quality from night to night.

PMID- 22479258
TI  - KSHV Induction of Angiogenic and Lymphangiogenic Phenotypes.
AB  - Kaposi's sarcoma (KS) is a highly vascularized tumor supporting large amounts of
      neo-angiogenesis. The major cell type in KS tumors is the spindle cell, a cell
      that expresses markers of lymphatic endothelium. KSHV, the etiologic agent of KS,
      is found in the spindle cells of all KS tumors. Considering the extreme extent of
      angiogenesis in KS tumors at all stages it has been proposed that KSHV directly
      induces angiogenesis in a paracrine fashion. In accordance with this theory, KSHV
      infection of endothelial cells in culture induces a number of host pathways
      involved in activation of angiogenesis and a number of KSHV genes themselves can
      induce pathways involved in angiogenesis. Spindle cells are phenotypically
      endothelial in nature, and therefore, activation through the induction of
      angiogenic and/or lymphangiogenic phenotypes by the virus may also be directly
      involved in spindle cell growth and tumor induction. Accordingly, KSHV infection
      of endothelial cells induces cell autonomous angiogenic phenotypes to activate
      host cells. KSHV infection can also reprogram blood endothelial cells to
      lymphatic endothelium. However, KSHV induces some blood endothelial specific
      genes upon infection of lymphatic endothelial cells creating a phenotypic
      intermediate between blood and lymphatic endothelium. Induction of pathways
      involved in angiogenesis and lymphangiogenesis are likely to be critical for
      tumor cell growth and spread. Thus, induction of both cell autonomous and non
      autonomous changes in angiogenic and lymphangiogenic pathways by KSHV likely
      plays a key role in the formation of KS tumors.

PMID- 22479259
TI  - Abiotic and Microbial Interactions during Anaerobic Transformations of Fe(II) and
      [Formula: see text].
AB  - Microbial Fe(II) oxidation using [Formula: see text] as the terminal electron
      acceptor [nitrate-dependent Fe(II) oxidation, NDFO] has been studied for over 15
      years. Although there are reports of autotrophic isolates and stable enrichments,
      many of the bacteria capable of NDFO are known organotrophic [Formula: see text]
      reducers that require the presence of an organic, primary substrate, e.g.,
      acetate, for significant amounts of Fe(II) oxidation. Although the thermodynamics
      of Fe(II) oxidation are favorable when coupled to either [Formula: see text] or
      [Formula: see text] reduction, the kinetics of abiotic Fe(II) oxidation by
      [Formula: see text] are relatively slow except under special conditions. NDFO is
      typically studied in batch cultures containing millimolar concentrations of
      Fe(II), [Formula: see text], and the primary substrate. In such systems,
      [Formula: see text] is often observed to accumulate in culture media during
      Fe(II) oxidation. Compared to [Formula: see text] abiotic reactions of biogenic
      [Formula: see text] and Fe(II) are relatively rapid. The kinetics and reaction
      pathways of Fe(II) oxidation by [Formula: see text] are strongly affected by
      medium composition and pH, reactant concentration, and the presence of Fe(II)
      sorptive surfaces, e.g., Fe(III) oxyhydroxides and cellular surfaces. In batch
      cultures, the combination of abiotic and microbial Fe(II) oxidation can alter
      product distribution and, more importantly, results in the formation of
      intracellular precipitates and extracellular Fe(III) oxyhydroxide encrustations
      that apparently limit further cell growth and Fe(II) oxidation. Unless steps are
      taken to minimize or account for potential abiotic reactions, results of
      microbial NDFO studies can be obfuscated by artifacts of the chosen experimental
      conditions, the use of inappropriate analytical methods, and the resulting
      uncertainties about the relative importance of abiotic and microbial reactions.
      In this manuscript, abiotic reactions of [Formula: see text] and [Formula: see
      text] with aqueous Fe(2+), chelated Fe(II), and solid-phase Fe(II) are reviewed
      along with factors that can influence overall NDFO reaction rates in microbial
      systems. In addition, the use of low substrate concentrations, continuous-flow
      systems, and experimental protocols that minimize experimental artifacts and
      reduce the potential for under- or overestimation of microbial NDFO rates are
      discussed.

PMID- 22479260
TI  - Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane
      Active Antiseptic Agent Against Candida albicans Biofilms.
AB  - Carbohydrate derived fulvic acid (CHD-FA) is a heat stable low molecular weight,
      water soluble, cationic, colloidal material with proposed therapeutic properties.
      The aim of this study was to evaluate the antifungal activity of CHD-FA against
      Candida albicans, and to characterize its mode of action. A panel of C. albicans
      isolates (n = 50) derived from a range of clinical specimens were grown
      planktonically and as biofilms, and the minimum inhibitory concentrations
      determined. Scanning electron microscopy was performed to examine ultrastructural
      changes and different cell membrane assays were used to determine its mode of
      action. In addition, the role of C. albicans biofilm resistance mechanisms were
      investigated to determine their effects on CHD-FA activity. CHD-FA was active
      against planktonic and sessile C. albicans at concentrations 0.125 and 0.25%
      respectively, and was shown to be fungicidal, acting through disruption of the
      cell membrane activity. Resistance mechanisms, including matrix, efflux, and
      stress, had a limited role upon CHD-FA activity. Overall, based on the promising
      in vitro spectrum of activity and minimal biofilm resistance of the natural and
      cheap antiseptic CHD-FA, further studies are required to determine its
      applicability for clinical use.

PMID- 22479261
TI  - The use of N-terminal pro-brain natriuretic Peptide to evaluate vascular disease
      in elderly patients with mental illness.
AB  - BACKGROUND: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is
      regarded as a sensitive marker of cardiovascular disease. Vascular disease plays
      an important role in cognitive impairment. METHOD: In 447 elderly patients with
      mental illness, serum NT-proBNP level and the presence or absence of vascular
      disease according to the medical record were used to categorize patients in
      different subgroups of vascular disease. RESULTS AND CONCLUSION: Patients with
      vascular disease and elevated serum NT-proBNP level had a lower cognition level,
      shorter survival time, lower renal function and a higher percentage of
      pathological brain imaging than patients with vascular disease and normal NT
      proBNP level. Thus, elevated serum NT-proBNP level might be helpful to detect
      patients who have a more severe cardiovascular disease.

PMID- 22479262
TI  - Factors associated with a depressive disorder in Alzheimer's disease are
      different from those found for other dementia disorders.
AB  - BACKGROUND: This study explores factors associated with depression in Alzheimer's
      disease (AD) compared with mild cognitive impairment (MCI) and other dementia
      disorders. METHOD: In a prospective study we included 195 patients: 31 with MCI,
      112 with AD and 52 with other dementias. RESULTS: According to the ICD-10 and the
      DSM-IV criteria, 88 (44.1%) and 59 (30.3%), respectively, had a depressive
      disorder. An adjusted multiple regression analysis showed that previous
      depression (p < 0.05) was significantly associated with depression in AD
      patients. Severity of dementia (p < 0.05) was significantly associated with a
      depressive disorder in a group of patients with frontotemporal dementia, vascular
      dementia, or dementia due to Lewy Body disease or Parkinson's disease.
      CONCLUSION: We found different factors associated with a depressive disorder in
      AD compared to those found for other dementia disorders.

PMID- 22479263
TI  - Thrombin stimulates synthesis of macrophage colony-stimulating factor,
      granulocyte-macrophage colony-stimulating factor and granulocyte colony
      stimulating factor by human proximal tubular epithelial cells in culture.
AB  - BACKGROUND/AIMS: Colony-stimulating factors (CSFs) are well-known hematopoietic
      growth factors. Although recent studies revealed that CSFs are involved in many
      inflammatory conditions, the local production of CSFs and its regulation in the
      kidney is not well elucidated. Therefore, using cultured human proximal tubular
      epithelial cells (PTEC), we examined the effect of thrombin on CSFs production,
      since thrombin has been suggested to play an important role in tubulointerstitial
      injury. METHODS: PTEC were incubated with thrombin (0.5-5.0 U/ml) and the effects
      on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF)
      and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme
      linked immunosorbent assay, and the expressions of mRNA were analyzed by
      quantitative real-time reverse transcription polymerase chain reaction. Using
      argatroban, a direct thrombin inhibitor, we also examined the specific effect of
      thrombin. RESULTS: Thrombin 5.0 U/ml significantly stimulated the production of M
      CSF (p < 0.01) and G-CSF (p < 0.01), and 1.0 and 5.0 U/ml thrombin significantly
      stimulated GM-CSF (p < 0.02 and p < 0.01) in a dose-dependent manner. Thrombin
      5.0 U/ml increased CSFs (M-CSF, p < 0.005; GM-CSF, p < 0.0005; G-CSF, p < 0.005)
      in a time-dependent manner. Thrombin also significantly enhanced the mRNA
      expressions of M-CSF (p < 0.01), GM-CSF (p < 0.05) and G-CSF (p < 0.01). These
      effects of thrombin were significantly reduced by the addition of argatroban (M
      CSF, p < 0.01; GM-CSF, p < 0.01; G-CSF, p < 0.05). CONCLUSION: We demonstrated
      that thrombin significantly increased the production of CSFs by PTEC. These data
      suggest that the local production of CSFs in the tubulointerstitium may affect
      tubulointerstitial lesions in kidney injury.

PMID- 22479264
TI  - ACE Inhibition in Anti-Thy1 Glomerulonephritis Limits Proteinuria but Does Not
      Improve Renal Function and Structural Remodeling.
AB  - BACKGROUND/AIMS: ACE inhibitor (ACE-I) treatment effectively inhibits proteinuria
      and ameliorates the course of various renal diseases. In experimental
      glomerulonephritis, however, angiotensin II (AngII) infusion has also been shown
      to be renoprotective. We evaluated the long-term (28 days) course of anti-Thy1
      glomerulonephritis in animals with suppressed AngII formation by ACE-I treatment.
      METHODS: Brown Norway rats received perindopril (2.8 mg/kg/day, n = 12),
      dihydropyridine calcium-antagonist amlodipine (Ca-A; 13 mg/kg/day, n = 6) or were
      left untreated (n = 14). All animals were monitored for blood pressure,
      proteinuria, and creatinine clearance after anti-Thy1 injection. Renal histology
      was assessed at day 7 and 28. RESULTS: Systolic blood pressure was equally
      reduced by ACE-I and Ca-A treatment. AngII suppression prevented development of
      proteinuria, but did not protect against glomerular microaneurysm formation or
      reduction in creatinine clearance. After resolution of the microaneurysms,
      animals with suppressed AngII production showed a modest increase in
      glomerulosclerosis and vasculopathic thickening of intrarenal vessels.
      CONCLUSIONS: In anti-Thy1 glomerulonephritis, suppression of AngII formation does
      not protect against the induction of glomerular damage and is associated with
      mild aggravation of adverse renal fibrotic remodeling. Proteinuria, however, is
      effectively prevented by ACE-I treatment. Ca-A treatment did not affect the
      course of glomerulonephritis, indicating that ACE-I effects are blood pressure
      independent.

PMID- 22479265
TI  - Mineralocorticoid Receptor Blocker Protects against Podocyte-Dependent
      Glomerulosclerosis.
AB  - BACKGROUND: We previously showed that angiotensin type 1 receptor (AT1) blocker
      (ARB) attenuates glomerular injury in Nphs1-hCD25 (NEP25) transgenic mice, a
      model of selective podocyte injury. However, subsequent studies in NEP25 mice
      with podocyte-specific deficiency of AT1 revealed that the protective effects of
      ARB are not through the podocyte AT1, thereby raising the possibility that the
      protective effects of ARB involve mineralocorticoids. METHODS: NEP25 mice were
      treated with the mineralocorticoid receptor blocker (MRB) spironolactone (25
      mg/kg/day, n = 10), the ARB losartan (250 mg/kg/day, n = 11), both (ARB+MRB, n =
      8) or vehicle (Vehicle, n = 9) from day -7 to day 9 of induction of podocyte
      injury. RESULTS: ALTHOUGH MRB DID NOT REDUCE SYSTOLIC BLOOD PRESSURE OR
      PROTEINURIA, ADDITION OF MRB TO ARB SIGNIFICANTLY ATTENUATED GLOMERULOSCLEROSIS
      (GLOMERULOSCLEROSIS INDEX: ARB+MRB 1.67 +/- 0.19 vs. MRB 2.01 +/- 0.29, ARB 2.35
      +/- 0.19, and Vehicle 2.25 +/- 0.26, p < 0.05) and preserved the number of WT1
      positive podocytes (ARB+MRB 152.5 +/- 9.7 vs. MRB 117.2 +/- 9.0 or ARB 113.6 +/-
      7.4, and ARB+MRB vs. Vehicle 97.5 +/- 4.0 per glomerulus; p < 0.05). CONCLUSION:
      These data suggest that, while MRB does not attenuate proteinuria caused by
      podocyte-specific injury, it provides protective effects against
      glomerulosclerosis that is independent of systemic blood pressure.

PMID- 22479266
TI  - Fas Ligand Has a Greater Impact than TNF-alpha on Apoptosis and Inflammation in
      Ischemic Acute Kidney Injury.
AB  - BACKGROUND/AIM: Fas ligand (FasL) and tumor necrosis factor (TNF)-alpha are major
      pro-apoptotic molecules and also induce inflammation through cytokine and
      chemokine production. Although precise intracellular mechanisms of action have
      been reported for each molecule, the differential impact of these molecules on
      kidney injury in vivo still requires clarification. METHODS: We explored the
      differential impact of FasL and TNF-alpha upon apoptosis and inflammation in
      ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF
      alpha receptor 1 (TNFR1)-deficient mice. RESULTS: TNFR1 deficiency was associated
      with a lesser anti-inflammatory effect upon leukocyte infiltration and tubular
      necrosis than treatment with anti-FasL antibody. Furthermore, the number of TUNEL
      positive cells was significantly reduced in anti-FasL antibody-treated mice,
      whereas it was only partially diminished in TNFR1-deficient mice. In vitro
      studies confirmed these findings. FasL administration induced both apoptosis and
      cytokine/chemokine production from cultured tubular epithelial cells. However,
      TNF-alpha had a limited effect upon tubular epithelial cells. CONCLUSION: In
      ischemic acute kidney injury, FasL has a greater impact than TNF-alpha on the
      apoptosis and inflammatory reaction through cytokine/chemokine production from
      tubular epithelial cells.

PMID- 22479267
TI  - Evaluation of Bovine chemerin (RARRES2) Gene Variation on Beef Cattle Production
      Traits.
AB  - A previous study in cattle based on >48,000 markers identified markers on
      chromosome 4 near the chemerin gene associated with average daily feed intake
      (ADFI) in steers (P < 0.008). Chemerin is an adipokine associated with obesity
      and metabolic syndrome in humans, representing a strong candidate gene
      potentially underlying the observed association. To evaluate whether the bovine
      chemerin gene is involved in feed intake, 16 markers within and around the gene
      were tested for association in the same resource population. Eleven were
      nominally significant for ADFI (P < 0.05) and two were significant after
      Bonferroni correction. Two and five SNP in this region were nominally significant
      for the related traits of average daily gain (ADG) and residual feed intake
      (RFI), respectively. All markers were evaluated for effects on meat quality and
      carcass phenotypes. Many of the markers associated with ADFI were associated with
      hot carcass weight (HCW), adjusted fat thickness (AFT), and marbling (P < 0.05).
      Marker alleles that were associated with lower ADFI were also associated with
      lower HCW, AFT, and marbling. Markers associated with ADFI were genotyped in a
      validation population of steers representing 14 breeds to determine predictive
      merit across populations. No consistent relationships for ADFI were detected. To
      determine whether cattle feed intake or growth phenotypes might be related to
      chemerin transcript abundance, the expression of chemerin was evaluated in
      adipose of 114 heifers that were siblings of the steers in the discovery
      population. Relative chemerin transcript abundance was not correlated with ADFI,
      ADG, or RFI, but associations with body condition score and yearling weight were
      observed. We conclude that variation in the chemerin gene may underlie observed
      association in the resource population, but that additional research is required
      to determine if this variation is widespread among breeds and to develop robust
      markers with predictive merit across breeds.

PMID- 22479268
TI  - Evolutionary and Biochemical Aspects of Chemical Stress Resistance in
      Saccharomyces cerevisiae.
AB  - Large-scale chemical genetics screens (chemogenomics) in yeast have been widely
      used to find drug targets, understand the mechanism-of-action of compounds, and
      unravel the biochemistry of drug resistance. Chemogenomics is based on the
      comparison of growth of gene deletants in the presence and absence of a chemical
      substance. Such studies showed that more than 90% of the yeast genes are required
      for growth in the presence of at least one chemical. Analysis of these data,
      using computational approaches, has revealed non-trivial features of the natural
      chemical tolerance systems. As a result two non-overlapping sets of genes are
      seen to respectively impart robustness and evolvability in the context of natural
      chemical resistance. The former is composed of multidrug-resistance genes,
      whereas the latter comprises genes sharing chemical genetic profiles with many
      others. Recent publications showing the potential applications chemogenomics in
      studying the pharmacological basis of various drugs are discussed, as well as the
      expansion of chemogenomics to other organisms. Finally, integration of
      chemogenomics with sensitive sequence analysis and ubiquitination/phosphorylation
      data led to the discovery of a new conserved domain and important post
      translational modification pathways involved in stress resistance.

PMID- 22479269
TI  - The premier statistical report of hematologic malignancies in Korea.

PMID- 22479270
TI  - Allogeneic stem cell transplantation for neuroblastoma.

PMID- 22479271
TI  - Leukemic manifestation of anaplastic lymphoma kinase-negative-type anaplastic
      large-cell lymphoma.

PMID- 22479272
TI  - Chronic myeloid leukemia with extreme thrombocytosis.

PMID- 22479273
TI  - Treatment strategies for Hodgkin lymphoma recurring following autologous
      hematopoietic stem cell transplantation.
AB  - Hodgkin lymphoma (HL) represents one of the great success stories in hematology
      going from a uniformly fatal disease, to one that is curable in the vast majority
      of cases. Despite this success, some patients experience relapse. To address this
      unmet need a variety of agents, classes of drugs, and strategies have
      demonstrated activity in HL recurring after autologous hematopoietic stem cell
      transplantation. These include chemotherapeutics (gemcitabine-based combinations,
      bendamustine), histone deacetylase (HDAC) inhibitors (panobinostat),
      immunomodulatory agents (lenalidomide), mTOR inhiobitors (everolimus), monoclonal
      antibodies (rituximab), and antibody-drug conjugates (brentuximab vedotin) as
      well the potential of long-term disease control via allogeneic transplantation.
      Such advances reflect our increased understanding of the biology of HL and hold
      promise for continued improved outcomes for those suffering with this condition.

PMID- 22479274
TI  - Cellular immunotherapy using dendritic cells against multiple myeloma.
AB  - Cellular therapy with dendritic cells (DCs) is emerging as a useful
      immunotherapeutic tool to treat multiple myeloma (MM). DC-based idiotype
      vaccination was recently suggested to induce idiotype-specific immune responses
      in MM patients. However, the clinical results so far have been largely
      disappointing, and the clinical effectiveness of such vaccinations in MM still
      needs to be demonstrated. DC-based therapies against MM may need to be boosted
      with other sources of tumor-associated antigens, and potent DCs should be
      recruited to increase the effectiveness of treatment. DCs with both high
      migratory capacity and high cytokine production are very important for effective
      DC-based cancer vaccination in order to induce high numbers of Th1-type CD4(+) T
      cells and CD8(+) cytotoxic T lymphocytes. The tumor microenvironment is also
      important in the regulation of tumor cell growth, proliferation, and the
      development of therapeutic resistance after treatment. In this review, we discuss
      how the efficacy of DC vaccination in MM can be improved. In addition, novel
      treatment strategies that target not only myeloma cells but also the tumor
      microenvironment are urgently needed to improve treatment outcomes.

PMID- 22479275
TI  - Statistics of hematologic malignancies in Korea: incidence, prevalence and
      survival rates from 1999 to 2008.
AB  - BACKGROUND: The nationwide statistical analysis of hematologic malignancies in
      Korea has not been reported yet. METHODS: The Korea Central Cancer Registry and
      the Korean Society of Hematology jointly investigated domestic incidence rates
      and prevalence of hematologic malignancies occurred between 1999 and 2008, and
      analyzed survival rates of patients who were diagnosed between 1993 and 2008.
      Data of hematologic malignancies from 1993 to 2008 were obtained from the Korean
      National Cancer Incidence Data base. The crude incidence rates, age-specific
      incidence rates, age-standardized incidence rates, annual percentage change of
      incidence, and prevalence from 1999-2008 were calculated. Survival rates for
      patients diagnosed in 1993-2008 were estimated. RESULTS: In 2008, a total of
      8,006 cases of hematologic malignancies were occurred, which comprised 4.5% of
      all malignancies. In all genders, non-Hodgkin lymphoma, myeloid leukemia, and
      multiple myeloma were most frequent diseases. In terms of age, ages between 60
      and 69 were most prevalent. From 1999 to 2008, the age-standardized incidence
      rates increased from 10.2 to 13.7, and the annual percentage change was 3.9%. The
      5-year survival rate increased from 38.2% during 1993-1995 to 55.2% during 2004
      2008. As of January 2009, number of patients with 10-year prevalence was 33,130,
      and with 5- to 10-year prevalence was 10,515. CONCLUSION: This is the first
      nationwide statistical report of hematologic malignancies in Korea. It could be
      used as the basic information to help investigate epidemiologic characteristics,
      evaluate progress during the past years, and establish future strategies for
      hematologic malignancies. Periodic statistical analysis of hematologic
      malignancies in Korea should be continued.

PMID- 22479276
TI  - Usefulness of anti-PF4/heparin antibody test for intensive care unit patients
      with thrombocytopenia.
AB  - BACKGROUND: It is critical to differentiate heparin-induced thrombocytopenia
      (HIT) from disseminated intravascular coagulation (DIC) in heparinized intensive
      care unit (ICU) patients with thrombocytopenia because the therapeutic approach
      differs based on the cause. We investigated the usefulness of PF4/heparin
      antibody tests in these patients. METHODS: A total of 127 heparinized ICU
      patients whose platelet counts were <150*10(9)/L or reduced by >50% after 5-10
      days of heparin therapy were enrolled. PF4/heparin antibodies were measured using
      2 immunoassays. We assessed the probability of HIT by using Warkentin's 4T's
      scoring system for antibody positive patients and compared routinely performed
      coagulation test results between patients with and without antibodies to evaluate
      the ability of these tests to discriminate between HIT and DIC. RESULTS: Positive
      results were obtained for 14 (11.0%) and 11 (8.7%) patients in the 2 assays. The
      analysis performed using the 4T's scoring system revealed that 11 of 20 (15.7%)
      patients with antibodies in at least 1 assay had intermediate or greater
      probability of HIT. Patients without antibodies had significantly higher levels
      of D-dimer than those with antibodies. However, there were no intergroup
      differences in platelet counts, PT, aPTT, fibrinogen, DIC score, and rate of
      overt DIC. CONCLUSION: Seropositivity for PF4/heparin antibody was 8.7-11.0% in
      the patients with thrombocytopenia, and more than a half of them had an increased
      probability of HIT. Among the routine coagulation tests, only D-dimer was
      informative for differentiating HIT from DIC. PF4/heparin antibody test is useful
      to ensure appropriate treatment for thrombocytopenic heparinized ICU patients.

PMID- 22479277
TI  - Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem
      cell transplantation in children.
AB  - BACKGROUND: Immune reconstitution (IR) after hematopoietic stem cell
      transplantation (HSCT) reduces transplantation-related complications such as
      infection and improves HSCT outcomes. METHODS: We retrospectively analyzed IR of
      lymphocyte subpopulations in 38 pediatric patients for hematologic malignant
      diseases after allogeneic HSCT from April 2006 to July 2008. T-cell-, B-cell-,
      and natural killer (NK) cell-associated antigens were assayed in peripheral blood
      by flow cytometry analysis of 5 lymphocyte subsets, CD3+, CD3+/CD4+, CD4+/CD8+,
      CD16+/CD56+, and CD19+, before and 3 and 12 months after transplantation.
      RESULTS: Reconstitutions of CD16+/CD56+ and CD3+/CD8+ lymphocytes were achieved
      rapidly, whereas that of CD3+/CD19+ lymphocytes occurred later. Age was not
      related to reconstitution of any lymphocyte subset. Total body irradiation (TBI)
      and anti-thymocyte globulin (ATG) administration were related to delayed
      reconstitution of total lymphocytes and CD3+ lymphocytes, respectively.
      Reconstitutions of CD3+/CD4+ lymphocytes and CD3+/CD8+ lymphocytes were
      significantly delayed in patients who received umbilical cord blood stem cells.
      In patients with chronic graft-versus-host disease (cGVHD), recovery of the total
      lymphocyte count and CD19+ lymphocytes at 3 months post-transplant were
      significantly delayed. However, acute GVHD (aGVHD) and cytomegalovirus (CMV)
      reactivation did not influence the IR of any lymphocyte subset. Further, delayed
      reconstitution of lymphocyte subsets did not correspond to inferior survival
      outcomes in this study. CONCLUSION: We observed that some lymphocyte
      reconstitutions after HSCT were influenced by the stem cell source and
      preparative regimens. However, delayed CD19+ lymphocyte reconstitution may be
      associated with cGVHD.

PMID- 22479278
TI  - A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients
      with advanced-stage diffuse large B-cell lymphomas.
AB  - BACKGROUND: Bortezomib targets molecular dysregulation of nuclear factor-kappaB
      activation and cell cycle control, which are characteristic features of diffuse
      large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib
      treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and
      prednisone (CHOP) every 2 weeks (CHOP-14). METHODS: Untreated DLBCL patients were
      enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m(2)
      bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was
      performed to determine the maximum tolerated dose (MTD) and the dose-limiting
      toxicity (DLT). Lenograstim 5 ug/kg/d was administered on day 4-13. The
      bortezomib dose from the phase I study was used in the phase II study. RESULTS:
      Nine and 37 patients were enrolled in the phase I and phase II studies,
      respectively. The analysis of the phase II results (40 patients) included data of
      the 3 patients in the last MTD dose cohort of the phase I trial. During the phase
      I trial, no DLT was observed at any bortezomib dose; therefore, the recommended
      dose was 1.6 mg/m(2). In phase II, the overall response rate was 95% (complete
      response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3
      sensory neuropathy, and 22 required at least 1 dose reduction. Three patients
      could not complete the intended 6 cycles of treatment because of severe
      neuropathy. CONCLUSION: Bortezomib plus CHOP-14 was highly effective for the
      treatment of untreated DLBCL patients, but in many cases, dose or schedule
      modification was required to reduce neurotoxicity.

PMID- 22479279
TI  - Relapse pattern and prognostic factors for patients with primary central nervous
      system lymphoma.
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) rarely relapses in
      extracranial sites, and no specialized guidelines for follow-up evaluation have
      been proposed. METHODS: We analyzed 65 patients with newly diagnosed PNCSL to
      evaluate the pattern of relapse and prognostic factors. RESULTS: Of the 65
      patients analyzed, 55 had only parenchymal brain disease, and 10 had both
      intracranial and extracranial lesions. As a first-line treatment, 29 patients
      received chemotherapy only (CTx), 13 received chemotherapy followed by whole
      brain radiotherapy (CTx-WBRT), 18 received chemotherapy followed by autologous
      stem cell transplantation (CTx-ASCT), 2 received palliative WBRT, and 3 received
      best supportive care. The overall response rate to the initial treatment was
      75.8%, with specific response rates of 62.1% to CTx, 84.6% to CTx-WBRT, and 100%
      to CTx-ASCT. The complete response (CR) rate was higher with CTx-ASCT than in the
      absence of ASCT (77.8% vs. 43.2%; P=0.025). After a median follow-up of 18.8
      months, the median failure-free survival (FFS) and overall survival (OS) were
      13.0 and 36.1 months, respectively. No systemic relapse without a CNS lesion was
      noted. Multivariate analysis showed that ASCT was predictive of better FFS but
      not of OS. Age and the Memorial-Sloan Kettering Cancer Center prognostic score
      were predictive of survival. CONCLUSION: We observed no systemic relapse without
      a CNS lesion, suggesting that regular systematic evaluation of extracranial sites
      may not always be necessary. Age was prognostic of survival irrespective of
      treatment scheme. ASCT may improve CR rate and FFS.

PMID- 22479280
TI  - Anti-leukemic and immunomodulatory effects of fungal metabolites of Pleurotus
      pulmonarius and Pleurotus ostreatus on benzene-induced leukemia in Wister rats.
AB  - BACKGROUND: The use of natural bioactive compounds in conventional chemotherapy
      is a new direction in cancer treatment that is gaining more research attention
      recently. Bioactive polysaccharides and polysaccharide-protein complexes from
      some fungi (edible mushrooms) have been identified as sources of effective and
      non-toxic antineoplastic agents. Selected oyster mushrooms (Pleurotus pulmonarius
      and P. ostreatus being local [Nigeria] and exotic strains, respectively) were
      cultured on a novel medium of yeast extract supplemented with an ethanolic
      extract of Annona senegalensis, and the antileukemic potential of their
      metabolites was studied. METHODS: Leukemia was successfully induced in Wister
      rats by intravenous injection (0.2 mL) of a benzene solution every 2 days for 3
      consecutive weeks. The aqueous solution of fungal metabolites (20 mg/mL) produced
      by submerged fermentation was orally administered (0.2 mL) before, during, and
      after leukemia induction. Leukemia burden was assessed by comparing the
      hematological parameters at baseline and after leukemia induction. The
      immunomodulatory potential of the metabolites was assessed by using a phagocytic
      assay (carbon clearance method). The ability to enhance leukopoiesis was assessed
      by using the total leukocyte count. RESULTS: Leukemia induction resulted in
      significant anemia indices and leukocytosis (P<0.05) in the experimental rats.
      Both metabolites equally enhanced leukopoiesis and demonstrated phagocytic
      actions; P. ostreatus activity was significantly higher than that of P.
      pulmonarius (P<0.05). CONCLUSION: The metabolites exhibited profound antileukemic
      potential by suppressing leukemia and demonstrating immunotherapeutic activities
      on animals after oral administration in various experimental groups.

PMID- 22479281
TI  - Asymptomatic pneumatosis intestinalis following chemotherapy for B lymphoblastic
      leukemia with recurrent genetic abnormalities in an adolescent patient.
AB  - Pneumatosis intestinalis (PI) is a rare condition characterized by multiple
      pneumocysts in the submucosa or subserosa of the bowel. Here, we report a rare
      case of asymptomatic PI after chemotherapy induction in an 18-yr-old man with B
      lymphoblastic leukemia with recurrent genetic abnormalities. The patient was
      treated conservatively and recovered without complications. The possibility of PI
      should be considered as a complication during or after chemotherapy for
      hematologic malignancies. Conservative treatment should be considered unless
      there are complications, including peritonitis, bowel perforation, and severe
      sepsis.

PMID- 22479282
TI  - Histoplasmosis on bone marrow aspirate cytological examination associated with
      hemophagocytosis and pancytopenia in an AIDS patient.
AB  - A 38-year-old woman who presented with unexplained fever and pancytopenia was
      subjected to a bone marrow examination. Her bone marrow aspirate smear showed no
      obvious pathological finding except for the presence of hemophagocytosis and mild
      plasmacytosis. In view of hemophagocytosis, a thorough examination of the smear
      was conducted and revealed the presence of histoplasmosis. She was advised to
      undergo evaluation of her immunological status, and she tested positive for human
      immunodeficiency virus (HIV) infection. This case highlights that
      hemophagocytosis in the marrow may be an early sign of underlying disease, and
      that careful examination of bone marrow smears may reveal subtle infections. In
      addition, histoplasmosis with hemophagocytosis may be associated with
      pancytopenia, and hence, the HIV status of the patient should always be
      investigated.

PMID- 22479283
TI  - A patient with acquired hemophilia A induced by clopidogrel.
AB  - Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies
      against factor VIII (FVIII). Treatment with clopidogrel is a cause of AHA, but
      its clinical course is unknown. Recently, we treated a 65-year-old man who was
      hospitalized for cerebellar infarction and had a prolonged activated partial
      thromboplastin time (aPTT) with soft tissue oozing after 3 weeks of clopidogrel
      use. We terminated clopidogrel administration and transfused the patient with
      fresh frozen plasma. However, the aPTT increased up to 98.8 seconds, and the
      FVIII and FVIII inhibitor levels were <1% and 5.4 Bethesda units/mL,
      respectively. Clopidogrel-associated AHA was considered, and we began steroid
      treatment. Two months later, FVIII, FVIII inhibitor, and aPTT values were
      normalized. No further bleeding or aPTT prolongation has been reported during the
      2-year follow-up period. AHA should be considered in patients taking clopidogrel
      and experiencing bleeding, unless the platelet count and coagulation screen are
      normal.

PMID- 22479285
TI  - World family doctor day 19 may 2011.

PMID- 22479284
TI  - "Indeterminate lupus anticoagulant" as the third category.

PMID- 22479286
TI  - Traditional mental health training's effect on primary care physicians in Saudi
      Arabia.

PMID- 22479287
TI  - Interventions during pregnancy to lower the chances of postnatal depression among
      women from the Asian subcontinent.
AB  - Postnatal depression (PND) is a major psychiatric challenge to women's mental
      health worldwide. Particularly speaking of the Asian subcontinent i.e. India and
      Pakistan (Indo-Pak), many women suffer through PND but remain undiagnosed, which
      may be due to lack of knowledge and awareness about alteration in mood and
      thoughts during pregnancy and after delivery. Certain factors like low socio
      economic status, a history of marital violence and depression entail a higher
      risk of PND. In addition, one factor which remains neglected is the husband's
      knowledge about PND and his behaviour toward the woman suffering from PND. The
      husband's poor knowledge of PND and his attitude toward the mother play a vital
      role in the initiation of PND. Pre-delivery interventions focusing on a couple's
      knowledge of PND, the couple's mutual understanding/relationship and
      identification of the potential stressors for a depressive episode may be one way
      to reduce the incidence of PND among both women and men.

PMID- 22479289
TI  - Does religious affiliation influence glycaemic control in primary care patients
      with type 2 diabetes mellitus?
AB  - Background To determine the relationships between religiosity, religions and
      glycaemic control of type 2 diabetes mellitus (T2D).Methods This is a cross
      sectional study conducted at an urban, university-based, teaching outpatient
      clinic. Religiosity was assessed with the Beliefs and Values Scale (BV), which
      contains 20 items each with a Likert scale of five possible responses. The range
      of scores is 0 to 80, with a higher score indicating stronger religious belief.
      Glycaemic control was taken as the mean value of the latest three fasting plasma
      glucose (FPG) levels and HbA1c readings documented in each patient's case
      records.Results A total of 212 patients participated (a response rate of 79%).
      Two-thirds were female, mean age was 62.7 (SD 10.8) years and mean duration of
      T2D was 11.7 (SD 6.7) years. The mean BV score was 57.4 (SD 10.97, CI 55.9,
      59.0). Religiosity had a negative correlation with lower FPG (r = -0.15, p =
      0.041) but no such correlation was found with HbA1c. Moslem religiosity had a
      significant negative correlation with HbA1c (r = -0.34, p = 0.007, n = 61) even
      after controlling for covariates. Christians and non-religious group had
      significantly lower mean rank HbA1c than other religions (p = 0.042).Conclusions
      Those with higher religiosity amongst the Moslem population had significantly
      better glycaemic control. Patients who had church-going religions had better
      glycaemic control compared with those of other religions.

PMID- 22479288
TI  - Detecting psychogeriatric problems in primary care: factors related to
      psychiatric symptoms in older community patients.
AB  - Objective The aim was to determine the relationship and influence of different
      variables on the psychiatric symptomatology of older people who reside in the
      community, as detected by family practitioners.Design A cross-sectional and multi
      centre study.Setting Twenty-eight general practices and two psychiatric practices
      in Huesca, Spain, from 19 primary care health centres.Subjects A sample of 324
      patients aged over 65 years, representative of the older people who reside in the
      community in the province of Huesca.Main outcome measures Symptoms of depression
      (Yesavage GDS), cognitive impairment (MMSE), anxiety (GADS), psychotic symptoms,
      obsessive symptoms and hypochondriacal ideas (GMS) were measured by family
      practitioner and were detected following specific questions from the Geriatric
      Mental State (GMS-B) examination, following DSM-IV criteria, being defined as
      'concern and fear of suffering, or the idea of having a serious disease based on
      the interpretation of somatic symptoms'. Sociodemographic, physical and somatic,
      functional and social data were evaluated. Analysis was carried out in three
      phases: univariate, bivariate and multivariate with logistic regression.Results
      At the time of the study, 46.1% of the older people studied suffered from some
      psychiatric symptom; 16.4% had cognitive impairment, 15.7% anxiety, 14.3%
      depression, 6.1% hallucinations and delusions, 7.2% hypochondriacal ideas and
      4.4% obsessive symptoms. Female gender was significantly associated with
      depression (prevalence ration (PR) 3.3) and anxiety (PR 3.9). Age was a factor
      associated with cognitive impairment (PR 4.4). Depression was significantly
      related to severity of the physical illness (PR 61.7 in extremely severe
      impairment). Isolation (PR 16.3) and being single (PR 13.4) were factors which
      were strongly associated with anxiety; living in a nursing home was associated
      with psychotic symptoms (PR 7.6).Conclusions Severity of physical illness,
      isolation, living in a nursing home and female gender, among others, are related
      to psychiatric symptoms in community-residing older people identified in primary
      healthcare centres.

PMID- 22479290
TI  - Compiling a register of patients with moderate or severe learning disabilities:
      experience at one United Kingdom general practice.
AB  - Background Identifying patients with learning disabilities within primary care is
      central to initiatives for improving the health of this population. UK general
      practitioners (GPs) receive additional income for maintaining registers of
      patients with learning disabilities as part of the Quality and Outcomes Framework
      (QOF), and may opt to provide Directed Enhanced Services (DES), which requires
      practices to maintain registers of patients with moderate or severe learning
      disabilities and offer them annual health checks.Objectives This paper describes
      the development of a register of patients with moderate or severe learning
      disabilities at one UK general practice.Methods A Read code search of one UK
      general practice's electronic medical records was conducted in order to identify
      patients with learning disabilities. Confirmation of diagnoses was sought by
      scrutinising records and GP verification. Cross-referencing with the practice QOF
      register of patients with learning disabilities of any severity, and the local
      authority's list of clients with learning disabilities, was performed.Results Of
      15 001 patients, 229 (1.5%) were identified by the Read code search as possibly
      having learning disabilities. Scrutiny of records and GP verification confirmed
      64 had learning disabilities and 24 did not, but the presence or absence of
      learning disability remained unclear in 141 cases. Cross-referencing with the QOF
      register (n=81) and local authority list (n=49) revealed little
      overlap.Conclusion Identifying learning disability and assessing its severity are
      tasks GPs may be unfamiliar with, and relying on Read code searches may result in
      under-detection. Further research is needed to define optimum strategies for
      identifying, cross-referencing and validating practice-based registers of
      patients with learning disabilities.

PMID- 22479291
TI  - Integrating mental health into primary health care in Iraq.
AB  - The Ministry of Health in Iraq is undertaking a systematic programme to integrate
      mental health into primary care in order to increase population access to mental
      health care. This paper reports the evaluation of the delivery of a ten day
      interactive training programme to 20% of primary care centres across Iraq. The
      multistage evaluation included a pre- and post-test questionnaire to assess
      knowledge, attitudes and practice in health workers drawn from 143 health
      centres, a course evaluation questionnaire and, in a random sample of 41 clinics,
      direct observation of health workers skills and exit interviews of patients,
      comparing health workers who had received the training programme with those from
      the same clinics who had not received the training. Three hundred andseventeen
      health workersparticipated in the training, which achieved an improvement in test
      scores from 42.3% to 59%. Trained health workers were observed by research
      psychiatrists to have a higher level of excellent skills than the untrained
      health workers, and patient exit interviews also reported better skills in the
      trained rather than untrained health workers. The two week course has thus been
      able to achieve significant change, not only in knowledge, but also in subsequent
      demonstration of trained practitioners practical skills in the workplace.
      Furthermore, it has been possible to implement the course and the evaluation
      despite a complex conflict situation.

PMID- 22479292
TI  - Suicide index reduction in Slovenia: the impact of primary care provision.
AB  - Background Education of primary care providers about diagnosis and treatment of
      depression and anxiety is an evidence-based suicide prevention measure.Aim To
      analyse suicide index, mental health epidemiological data and primary care
      provision in Slovenian regions and to identify examples of good suicide
      prevention practices in different Slovenian regions.Methods Analysis of existent
      epidemiological data on mental health in Slovenia.Results Anxiety and depression
      are the most common complaints in a representative sample of the Slovene
      population. The number of suicides in Slovenia had been dropping in the period
      from 2002 to 2006 and was again slowly rising in 2008. The number of visits to
      family physicians' practices because of mental health problems is low in
      comparison to other European countries, which might be attributed also to the
      high workload of family physicians. Suicide prevention programmes follow the
      example of the Suicide Prevention Project in the central-east region of Slovenia.
      This programme is based on education of primary care providers and the general
      public about recognition and treatment of depression in line with international
      guidelines.Conclusions The differentiation of causes for suicide reduction needs
      further research, as well as urgent improvement in the accessibility of primary
      care teams in Slovenia.

PMID- 22479293
TI  - Melorheostosis and its treatment with intravenous zoledronic acid.
AB  - We report a case of melorheostosis, a rare bone disorder characterised by
      mesodermal dysplasia, and its successful and prolonged treatment with the
      intravenous bisphosphonate zoledronic acid. The middle-aged man presented with
      pain and swelling of his tibia, which was diagnosed by imaging and bone biopsy as
      being due to melorheostosis. There was early symptom control after a single
      infusion of intravenous zoledronic acid. Prolonged symptom relief was accompanied
      by long-term suppression of the bone resorption marker beta cross-laps. We
      suggest that melorheostosis can be treated with intravenous zoledronic acid and
      that treatment can be monitored by the use of a specific bone resorption marker.

PMID- 22479294
TI  - Myasthenia gravis presenting as acute vocal cord paresis.
AB  - Myasthenia gravis is a condition rarely seen by otolaryngologists. We present a
      case of bilateral vocal cord paresis caused by previously undiagnosed myasthenia
      gravis. A tracheostomy was required after initial presentation and after a
      relapse. The airway management, neurological diagnosis and medical treatment are
      discussed.

PMID- 22479295
TI  - Concurrent macular oedema and optic neuritis in Crohn's disease with varied
      response to steroids.
AB  - A patient with a 10-year history of Crohn's disease presented to our
      ophthalmology service with symptoms of acute anterior uveitis. Previous episodes
      had been treated successfully with topical steroids.However, on this occasion
      after treatment with topical steroids, the patient developed macular oedema with
      concurrent optic neuritis in the affected eye.Furthermore, optic neuritis
      persisted despite oral steroid treatment contrary to expectations based on
      current literature. After 6 months of treatment, optic disc oedema had markedly
      improved but was replaced by sectoral disc pallor.

PMID- 22479296
TI  - Positive psoas sign in presentation of retroperitoneal malignant triton tumour.
AB  - This article describes a case of a rare malignant neoplasm presenting to the
      emergency department with common symptomatology and its subsequent identification
      using a simple physical examination technique. Discussion includes a description
      of this rare soft tissue sarcoma and a consideration of the value of the psoas
      sign as a part of the routine abdominal exam to detect intra-abdominal and
      retroperitoneal pathology. In conclusion, this article acts as a reminder to all
      clinicians that uncommon and significant pathology may present to the emergency
      department masquerading as a common, seemingly benign, complaint, but can be
      clinically identified using simple techniques available to all and rapidly
      investigated using appropriate special investigations.

PMID- 22479297
TI  - A case of needle fixation.
AB  - Needle fixation is frequently missed and dismissed by clinicians and patients.
      However, ignoring this condition can have severe consequences, such as
      septicaemia, thrombosis, blood borne viruses, and is associated with an overall
      poor prognosis of drug dependence.Here we describe a 37-year-old man who
      presented with 20-year history of polydrug dependence, drug-induced psychosis and
      antisocial personality disorder. He was found to also have a 5-year history of
      intermittent needle fixation. His injecting behaviour and drug use improved
      significantly with fluoxetine while being on methadone maintenance.At present
      there is little evidence for any effective treatment strategies for needle
      fixation. The current recommended treatment consists of cognitive behavioural
      therapy and cue exposure. Whether fluoxetine constitutes an effective management
      strategy remains to be seen.

PMID- 22479298
TI  - An unusual case of myocardial infarction.
AB  - POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin
      changes) syndrome is a rare haematological condition with a constellation of
      clinical features that can present to the clinician in a variety of ways. This
      case highlights how a seemingly uncomplicated myocardial infarction can herald
      the development of this rare haematological disorder. While knowledge of the
      pathophysiological mechanisms that underpin POEMS syndrome is developing, so too
      are the diagnostic and treatment strategies available to the clinician.

PMID- 22479299
TI  - Meckel diverticulum causing small bowel obstruction.
AB  - A 62-year-old man was admitted with generalised abdominal pain, constipation and
      vomiting. His abdomen was markedly distended and tender on general examination
      with signs of local peritonism in the left iliac fossa. He was initially
      diagnosed with likely acute diverticulitis and treated conservatively. A CT scan
      the next day showed fluid filled, dilated small bowel loops consistent with small
      bowel obstruction and there was a suggestion of an abscess in the left iliac
      fossa region. An urgent laparotomy was performed, which identified a perforated
      Meckel diverticulum.

PMID- 22479303
TI  - Highly parallel translation of DNA sequences into small molecules.
AB  - A large body of in vitro evolution work establishes the utility of biopolymer
      libraries comprising 10(10) to 10(15) distinct molecules for the discovery of
      nanomolar-affinity ligands to proteins. Small-molecule libraries of comparable
      complexity will likely provide nanomolar-affinity small-molecule ligands. Unlike
      biopolymers, small molecules can offer the advantages of cell permeability, low
      immunogenicity, metabolic stability, rapid diffusion and inexpensive mass
      production. It is thought that such desirable in vivo behavior is correlated with
      the physical properties of small molecules, specifically a limited number of
      hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most
      importantly, molecular weights less than 500 Daltons. Creating a collection of
      10(10) to 10(15) small molecules that meet these criteria requires the use of
      hundreds to thousands of diversity elements per step in a combinatorial synthesis
      of three to five steps. With this goal in mind, we have reported a set of
      mesofluidic devices that enable DNA-programmed combinatorial chemistry in a
      highly parallel 384-well plate format. Here, we demonstrate that these devices
      can translate DNA genes encoding 384 diversity elements per coding position into
      corresponding small-molecule gene products. This robust and efficient procedure
      yields small molecule-DNA conjugates suitable for in vitro evolution experiments.

PMID- 22479304
TI  - Disentangling the relative importance of changes in climate and land-use
      intensity in driving recent bird population trends.
AB  - Threats to biodiversity resulting from habitat destruction and deterioration have
      been documented for many species, whilst climate change is regarded as
      increasingly impacting upon species' distribution and abundance. However, few
      studies have disentangled the relative importance of these two drivers in causing
      recent population declines. We quantify the relative importance of both processes
      by modelling annual variation in population growth of 18 farmland bird species in
      the UK as a function of measures of land-use intensity and weather. Modelled
      together, both had similar explanatory power in accounting for annual
      fluctuations in population growth. When these models were used to retrodict
      population trends for each species as a function of annual variation in land-use
      intensity and weather combined, and separately, retrodictions incorporating land
      use intensity were more closely linked to observed population trends than
      retrodictions based only on weather, and closely matched the UK farmland bird
      index from 1970 onwards. Despite more stable land-use intensity in recent years,
      climate change (inferred from weather trends) has not overtaken land-use
      intensity as the dominant driver of bird populations.

PMID- 22479305
TI  - Response inhibition during cue reactivity in problem gamblers: an fMRI study.
AB  - Disinhibition over drug use, enhanced salience of drug use and decreased salience
      of natural reinforcers are thought to play an important role substance
      dependence. Whether this is also true for pathological gambling is unclear. To
      understand the effects of affective stimuli on response inhibition in problem
      gamblers (PRGs), we designed an affective Go/Nogo to examine the interaction
      between response inhibition and salience attribution in 16 PRGs and 15 healthy
      controls (HCs).Four affective blocks were presented with Go trials containing
      neutral, gamble, positive or negative affective pictures. The No-Go trials in
      these blocks contained neutral pictures. Outcomes of interest included percentage
      of impulsive errors and mean reaction times in the different blocks. Brain
      activity related to No-Go trials was assessed to measure response inhibition in
      the various affective conditions and brain activity related to Go trials was
      assessed to measure salience attribution.PRGs made fewer errors during gamble and
      positive trials than HCs, but were slower during all trials types. Compared to
      HCs, PRGs activated the dorsolateral prefrontal cortex, anterior cingulate and
      ventral striatum to a greater extent while viewing gamble pictures. The dorsal
      lateral and inferior frontal cortex were more activated in PRGs than in HCs while
      viewing positive and negative pictures. During neutral inhibition, PRGs were
      slower but similar in accuracy to HCs, and showed more dorsolateral prefrontal
      and anterior cingulate cortex activity. In contrast, during gamble and positive
      pictures PRGs performed better than HCs, and showed lower activation of the
      dorsolateral and anterior cingulate cortex.This study shows that gambling-related
      stimuli are more salient for PRGs than for HCs. PRGs seem to rely on compensatory
      brain activity to achieve similar performance during neutral response inhibition.
      A gambling-related or positive context appears to facilitate response inhibition
      as indicated by lower brain activity and fewer behavioural errors in PRGs.

PMID- 22479306
TI  - Impaired clearance and enhanced pulmonary inflammatory/fibrotic response to
      carbon nanotubes in myeloperoxidase-deficient mice.
AB  - Advancement of biomedical applications of carbonaceous nanomaterials is hampered
      by their biopersistence and pro-inflammatory action in vivo. Here, we used
      myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation
      and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these
      animals after pharyngeal aspiration was markedly less effective whereas the
      inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results
      provide direct evidence for the participation of MPO - one of the key
      orchestrators of inflammatory response - in the in vivo pulmonary oxidative
      biodegradation of SWCNT and suggest new ways to control the biopersistence of
      nanomaterials through genetic or pharmacological manipulations.

PMID- 22479307
TI  - Genetic ancestry, self-reported race and ethnicity in African Americans and
      European Americans in the PCaP cohort.
AB  - BACKGROUND: Family history and African-American race are important risk factors
      for both prostate cancer (CaP) incidence and aggressiveness. When studying
      complex diseases such as CaP that have a heritable component, chances of finding
      true disease susceptibility alleles can be increased by accounting for genetic
      ancestry within the population investigated. Race, ethnicity and ancestry were
      studied in a geographically diverse cohort of men with newly diagnosed CaP.
      METHODS: Individual ancestry (IA) was estimated in the population-based North
      Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident
      CaP cases (2063 with complete ethnicity information) comprising roughly equal
      numbers of research subjects reporting as Black/African American (AA) or European
      American/Caucasian/Caucasian American/White (EA) from North Carolina or
      Louisiana. Mean genome wide individual ancestry estimates of percent African,
      European and Asian were obtained and tested for differences by state and
      ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis
      of variance models. Principal components (PC) were compared to assess differences
      in genetic composition by self-reported race and ethnicity between and within
      states. RESULTS: Mean individual ancestries differed by state for self-reporting
      AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs
      who answered "no" to all ethnicity membership questions (non-ethnic research
      subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry
      estimates of self-identified AA Louisiana research subjects for each ethnic
      group; Cajun only, Creole only and both Cajun and Creole differed significantly
      from self-identified non-ethnic AA Louisiana research subjects. These ethnicity
      differences were not seen in those who self-identified as EA. CONCLUSIONS: Mean
      IA differed by race between states, elucidating a potential contributing factor
      to these differences in AA research participants: self-reported ethnicity.
      Accurately accounting for genetic admixture in this cohort is essential for
      future analyses of the genetic and environmental contributions to CaP.

PMID- 22479308
TI  - Mtss1 promotes cell-cell junction assembly and stability through the small GTPase
      Rac1.
AB  - Cell-cell junctions are an integral part of epithelia and are often disrupted in
      cancer cells during epithelial-to-mesenchymal transition (EMT), which is a main
      driver of metastatic spread. We show here that Metastasis suppressor-1 (Mtss1;
      Missing in Metastasis, MIM), a member of the IMD-family of proteins, inhibits
      cell-cell junction disassembly in wound healing or HGF-induced scatter assays by
      enhancing cell-cell junction strength. Mtss1 not only makes cells more resistant
      to cell-cell junction disassembly, but also accelerates the kinetics of adherens
      junction assembly. Mtss1 drives enhanced junction formation specifically by
      elevating Rac-GTP. Lastly, we show that Mtss1 depletion reduces recruitment of F
      actin at cell-cell junctions. We thus propose that Mtss1 promotes Rac1 activation
      and actin recruitment driving junction maintenance. We suggest that the observed
      loss of Mtss1 in cancers may compromise junction stability and thus promote EMT
      and metastasis.

PMID- 22479309
TI  - Genome-wide association study to identify common variants associated with
      brachial circumference: a meta-analysis of 14 cohorts.
AB  - Brachial circumference (BC), also known as upper arm or mid arm circumference,
      can be used as an indicator of muscle mass and fat tissue, which are distributed
      differently in men and women. Analysis of anthropometric measures of peripheral
      fat distribution such as BC could help in understanding the complex
      pathophysiology behind overweight and obesity. The purpose of this study is to
      identify genetic variants associated with BC through a large-scale genome-wide
      association scan (GWAS) meta-analysis. We used fixed-effects meta-analysis to
      synthesise summary results across 14 GWAS discovery and 4 replication cohorts
      comprising overall 22,376 individuals (12,031 women and 10,345 men) of European
      ancestry. Individual analyses were carried out for men, women, and combined
      across sexes using linear regression and an additive genetic model: adjusted for
      age and adjusted for age and BMI. We prioritised signals for follow-up in two
      stages. We did not detect any signals reaching genome-wide significance. The FTO
      rs9939609 SNP showed nominal evidence for association (p<0.05) in the age
      adjusted strata for men and across both sexes. In this first GWAS meta-analysis
      for BC to date, we have not identified any genome-wide significant signals and do
      not observe robust association of previously established obesity loci with BC.
      Large-scale collaborations will be necessary to achieve higher power to detect
      loci underlying BC.

PMID- 22479310
TI  - The myeloid receptor PILRbeta mediates the balance of inflammatory responses
      through regulation of IL-27 production.
AB  - Paired immunoglobulin-like receptors beta, PILRbeta, and alpha, PILRalpha, are
      related to the Siglec family of receptors and are expressed primarily on cells of
      the myeloid lineage. PILRbeta is a DAP12 binding partner expressed on both human
      and mouse myeloid cells. The potential ligand, CD99, is found on many cell types,
      such as epithelial cells where it plays a role in migration of immune cells to
      sites of inflammation. Pilrb deficient mice were challenged with the parasite
      Toxoplasma gondii in two different models of infection induced inflammation; one
      involving the establishment of chronic encephalitis and a second mimicking
      inflammatory bowel disease in order to understand the potential role of this
      receptor in persistent inflammatory responses. It was found that in the absence
      of activating signals from PILRbeta, antigen-presenting cells (APCs) produced
      increased amounts of IL-27, p28 and promoted IL-10 production in effector T
      cells. The sustained production of IL-27 led ultimately to enhanced survival
      after challenge due to dampened immune pathology in the gut. Similar protection
      was also observed in the CNS during chronic T. gondii infection after i.p.
      challenge again providing evidence that PILRbeta is important for regulating
      aberrant inflammatory responses.

PMID- 22479311
TI  - Walking is not like reaching: evidence from periodic mechanical perturbations.
AB  - The control architecture underlying human reaching has been established, at least
      in broad outline. However, despite extensive research, the control architecture
      underlying human locomotion remains unclear. Some studies show evidence of high
      level control focused on lower-limb trajectories; others suggest that nonlinear
      oscillators such as lower-level rhythmic central pattern generators (CPGs) play a
      significant role. To resolve this ambiguity, we reasoned that if a nonlinear
      oscillator contributes to locomotor control, human walking should exhibit dynamic
      entrainment to periodic mechanical perturbation; entrainment is a distinctive
      behavior of nonlinear oscillators. Here we present the first behavioral evidence
      that nonlinear neuro-mechanical oscillators contribute to the production of human
      walking, albeit weakly. As unimpaired human subjects walked at constant speed, we
      applied periodic torque pulses to the ankle at periods different from their
      preferred cadence. The gait period of 18 out of 19 subjects entrained to this
      mechanical perturbation, converging to match that of the perturbation.
      Significantly, entrainment occurred only if the perturbation period was close to
      subjects' preferred walking cadence: it exhibited a narrow basin of entrainment.
      Further, regardless of the phase within the walking cycle at which perturbation
      was initiated, subjects' gait synchronized or phase-locked with the mechanical
      perturbation at a phase of gait where it assisted propulsion. These results were
      affected neither by auditory feedback nor by a distractor task. However, the
      convergence to phase-locking was slow. These characteristics indicate that
      nonlinear neuro-mechanical oscillators make at most a modest contribution to
      human walking. Our results suggest that human locomotor control is not organized
      as in reaching to meet a predominantly kinematic specification, but is
      hierarchically organized with a semi-autonomous peripheral oscillator operating
      under episodic supervisory control.

PMID- 22479312
TI  - A systematic review of studies measuring and reporting hearing aid usage in older
      adults since 1999: a descriptive summary of measurement tools.
AB  - OBJECTIVE: A systematic review was conducted to identify and quality assess how
      studies published since 1999 have measured and reported the usage of hearing aids
      in older adults. The relationship between usage and other dimensions of hearing
      aid outcome, age and hearing loss are summarised. DATA SOURCES: Articles were
      identified through systematic searches in PubMed/MEDLINE, The University of
      Nottingham Online Catalogue, Web of Science and through reference checking. STUDY
      ELIGIBILITY CRITERIA: (1) participants aged fifty years or over with sensori
      neural hearing loss, (2) provision of an air conduction hearing aid, (3)
      inclusion of hearing aid usage measure(s) and (4) published between 1999 and
      2011. RESULTS: Of the initial 1933 papers obtained from the searches, a total of
      64 were found eligible for review and were quality assessed on six dimensions:
      study design, choice of outcome instruments, level of reporting (usage, age, and
      audiometry) and cross validation of usage measures. Five papers were rated as
      being of high quality (scoring 10-12), 35 papers were rated as being of moderate
      quality (scoring 7-9), 22 as low quality (scoring 4-6) and two as very low
      quality (scoring 0-2). Fifteen different methods were identified for assessing
      the usage of hearing aids. CONCLUSIONS: Generally, the usage data reviewed was
      not well specified. There was a lack of consistency and robustness in the way
      that usage of hearing aids was assessed and categorised. There is a need for more
      standardised level of reporting of hearing aid usage data to further understand
      the relationship between usage and hearing aid outcomes.

PMID- 22479313
TI  - HIV-related high-risk behaviors among Chinese migrant construction laborers in
      Nantong, Jiangsu.
AB  - BACKGROUND: HIV transmission in rural areas of China is being fueled in part by
      migrant workers who acquire HIV outside of their hometowns. Recent surveillance
      statistics indicate that HIV prevalence among returning migrants has increased
      significantly. METHODS: We conducted a community-based cross-sectional study to
      assess HIV-related knowledge, attitudes and behaviors among migrant returnees in
      Nantong, Jiangsu Province, one of the largest exporters of migrant laborers.
      RESULTS: A total of 1625 subjects were enrolled with a response rate of 89%. All
      participants were male and of the majority Han ethnicity. The mean age was 39.0
      years (SD = 6.7; range: 18 to 63), and most had a stable partner (N = 1533,
      94.3%). Most correctly identified the major modes of HIV transmission (68.9%
      82.0%), but fewer were able to identify ways that HIV cannot be transmitted.
      Nearly one-third of participants held positive attitudes toward having multiple
      sex partners, and nearly half believed that sex work should be legalized.
      Multiple logistic regression analysis indicated that risky sexual behavior
      (defined as sex with a casual or commercial sex partner) was associated with no
      stable partner; working abroad; correct condom use; age <22 at first sex; higher
      coital frequency; and having a positive attitude towards multiple sex partners.
      CONCLUSIONS: We found high levels of reported sex with a casual or commercial sex
      partner and low levels of consistent condom use. HIV prevention interventions
      among migrant workers need to focus on younger migrants, migrants without stable
      partners, and migrants who travel abroad for work.

PMID- 22479314
TI  - Streptococcus pneumoniae serotype-2 childhood meningitis in Bangladesh: a newly
      recognized pneumococcal infection threat.
AB  - BACKGROUND: Streptococcus pneumoniae is a leading cause of meningitis in
      countries where pneumococcal conjugate vaccines (PCV) targeting commonly
      occurring serotypes are not routinely used. However, effectiveness of PCV would
      be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by
      serotypes which are not included in PCV. Systematic hospital based surveillance
      in Bangladesh was established and progressively improved to determine the
      pathogens causing childhood sepsis and meningitis. This also provided the
      foundation for determining the spectrum of serotypes causing IPD. This article
      reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal
      serotype, without any known intervention. METHODS AND FINDINGS: Cases with
      suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning
      of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of
      isolates or PCR of culture-negative CSF specimens. Multicenter national
      surveillance, expanded from 2004, identified 45,437 patients with suspected
      bacteremia who were blood cultured and 10,618 suspected meningitis cases who had
      a lumber puncture. Pneumococcus accounted for 230 culture positive cases of
      meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal
      meningitis, accounting for 20.4% (45/221; 95% CI 15%-26%) of cases. Ninety eight
      percent (45/46) of these serotype-2 strains were isolated from meningitis cases,
      yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI
      3.4-256.3). The serotype-2 strains had three closely related pulsed field gel
      electrophoresis types. CONCLUSIONS: S. pneumoniae serotype-2 was found to possess
      an unusually high potential for causing meningitis and was the leading serotype
      specific cause of childhood meningitis in Bangladesh over the past decade.
      Persisting disease occurrence or progressive spread would represent a major
      potential infection threat since serotype-2 is not included in PCVs currently
      licensed or under development.

PMID- 22479315
TI  - Coupled analysis of in vitro and histology tissue samples to quantify structure
      function relationship.
AB  - The structure/function relationship is fundamental to our understanding of
      biological systems at all levels, and drives most, if not all, techniques for
      detecting, diagnosing, and treating disease. However, at the tissue level of
      biological complexity we encounter a gap in the structure/function relationship:
      having accumulated an extraordinary amount of detailed information about
      biological tissues at the cellular and subcellular level, we cannot assemble it
      in a way that explains the correspondingly complex biological functions these
      structures perform. To help close this information gap we define here several
      quantitative temperospatial features that link tissue structure to its
      corresponding biological function. Both histological images of human tissue
      samples and fluorescence images of three-dimensional cultures of human cells are
      used to compare the accuracy of in vitro culture models with their corresponding
      human tissues. To the best of our knowledge, there is no prior work on a
      quantitative comparison of histology and in vitro samples. Features are
      calculated from graph theoretical representations of tissue structures and the
      data are analyzed in the form of matrices and higher-order tensors using matrix
      and tensor factorization methods, with a goal of differentiating between
      cancerous and healthy states of brain, breast, and bone tissues. We also show
      that our techniques can differentiate between the structural organization of
      native tissues and their corresponding in vitro engineered cell culture models.

PMID- 22479316
TI  - Attentional performance, age and scholastic achievement in healthy children.
AB  - BACKGROUND: Attentional processes in children play a critical role in daily
      school demands and accomplishments. Studies on the association of attentional
      processes with school achievement and age in healthy school children are scarce.
      The aim of the present study was to identify correlations between dimensions of
      attentional performance, scholastic achievement and age. METHODOLOGY/PRINCIPAL
      FINDINGS: An extensive testing battery was used to assess a wide range of
      attentional dimensions. A principal component analysis revealed three factors
      that are related to attentional performance (distractibility, lapses of
      attention, cognitive speed). Age was negatively associated with distractibility,
      lapses of attention and cognitive speed, indicating that distractibility and
      lapses of attention decreased with age in healthy children and resulted in lower
      cognitive speed. CONCLUSIONS/SIGNIFICANCE: Attentional processes in healthy
      children should be measured in relation to distractibility, lapses of attention
      and cognitive speed.

PMID- 22479318
TI  - Mesofluidic devices for DNA-programmed combinatorial chemistry.
AB  - Hybrid combinatorial chemistry strategies that use DNA as an information-carrying
      medium are proving to be powerful tools for molecular discovery. In order to
      extend these efforts, we present a highly parallel format for DNA-programmed
      chemical library synthesis. The new format uses a standard microwell plate
      footprint and is compatible with commercially available automation technology. It
      can accommodate a wide variety of combinatorial synthetic schemes with up to 384
      different building blocks per chemical step. We demonstrate that fluidic routing
      of DNA populations in the highly parallel format occurs with excellent
      specificity, and that chemistry on DNA arrayed into 384 well plates proceeds
      robustly, two requirements for the high-fidelity translation and efficient in
      vitro evolution of small molecules.

PMID- 22479317
TI  - Modulation of gamma-secretase activity by multiple enzyme-substrate interactions:
      implications in pathogenesis of Alzheimer's disease.
AB  - BACKGROUND: We describe molecular processes that can facilitate pathogenesis of
      Alzheimer's disease (AD) by analyzing the catalytic cycle of a membrane-imbedded
      protease gamma-secretase, from the initial interaction with its C99 substrate to
      the final release of toxic Abeta peptides. RESULTS: The C-terminal AICD fragment
      is cleaved first in a pre-steady-state burst. The lowest Abeta42/Abeta40 ratio is
      observed in pre-steady-state when Abeta40 is the dominant product. Abeta42 is
      produced after Abeta40, and therefore Abeta42 is not a precursor for Abeta40. The
      longer more hydrophobic Abeta products gradually accumulate with multiple
      catalytic turnovers as a result of interrupted catalytic cycles. Saturation of
      gamma-secretase with its C99 substrate leads to 30% decrease in Abeta40 with
      concomitant increase in the longer Abeta products and Abeta42/Abeta40 ratio. To
      different degree the same changes in Abeta products can be observed with two
      mutations that lead to an early onset of AD, DeltaE9 and G384A. Four different
      lines of evidence show that gamma-secretase can bind and cleave multiple
      substrate molecules in one catalytic turnover. Consequently depending on its
      concentration, NotchDeltaE substrate can activate or inhibit gamma-secretase
      activity on C99 substrate. Multiple C99 molecules bound to gamma-secretase can
      affect processive cleavages of the nascent Abeta catalytic intermediates and
      facilitate their premature release as the toxic membrane-imbedded Abeta-bundles.
      CONCLUSIONS: Gradual saturation of gamma-secretase with its substrate can be the
      pathogenic process in different alleged causes of AD. Thus, competitive
      inhibitors of gamma-secretase offer the best chance for a successful therapy,
      while the noncompetitive inhibitors could even facilitate development of the
      disease by inducing enzyme saturation at otherwise sub-saturating substrate.
      Membrane-imbedded Abeta-bundles generated by gamma-secretase could be neurotoxic
      and thus crucial for our understanding of the amyloid hypothesis and AD
      pathogenesis.

PMID- 22479319
TI  - A syndemic of psychosocial problems places the MSM (men who have sex with men)
      population at greater risk of HIV infection.
AB  - BACKGROUND: The MSM (Men who have sex with men) population suffers from very high
      rates of concurrent psychosocial problems. Together, these problems comprise a
      syndemic that increases the risk of HIV infection for this community. The precise
      mechanisms through which this syndemic can raise the likelihood of HIV infection
      warrant further exploration. METHODOLOGY/PRINCIPAL FINDINGS: A total of 522 MSM
      were enrolled via a multiframe sampling approach and were asked to report
      psychosocial problems, risky sexual behaviors and HIV test results. A count of
      psychosocial health problems was calculated to test the additive relationship of
      these factors on HIV risk. Adjusting analysis and restriction analysis were used
      to determine a proposed intermediate pathway. Psychosocial health problems are
      highly concurrent and intercorrelated among urban MSM. Greater numbers of health
      problems are significantly and positively associated with HIV infection, which is
      mediated, at least partially, by risky sexual behaviors.
      CONCLUSIONS/SIGNIFICANCE: MSM experience concurrent psychosocial health problems
      that correlate with HIV infection in this community. We recommend the development
      of coping strategies for this population to deal with these psychosocial
      problems, both in prevention research and health policy.

PMID- 22479320
TI  - Willingness to accept HIV pre-exposure prophylaxis among Chinese men who have sex
      with men.
AB  - OBJECTIVE: We investigated the awareness and acceptability of pre-exposure
      prophylaxis (PrEP) among men who have sex with men (MSM) and potential predicting
      factors. METHODS: This study was conducted among MSM in Beijing, China. Study
      participants, randomly selected from an MSM cohort, completed a structured
      questionnaire, and provided their blood samples to test for HIV infection and
      syphilis. Univariate logistic regression analyses were performed to evaluate the
      factors associated with willingness to accept (WTA) PrEP. Factors independently
      associated with willingness to accept were identified by entering variables into
      stepwise logistic regression analysis. RESULTS: A total of 152 MSM completed the
      survey; 11.2% had ever heard of PrEP and 67.8% were willing to accept it.
      Univariate analysis showed that age, years of education, consistent condom use in
      the past 6 months, heterosexual behavior in the past 6 months, having ever heard
      of PrEP and the side effects of antiretroviral drugs, and worry about
      antiretroviral drugs cost were significantly associated with willingness to
      accept PrEP. In the multivariate logistic regression model, only consistent
      condom use in the past 6 months (odds ratio [OR]: 0.31; 95% confidence interval
      [CI]: 0.13-0.70) and having ever heard of the side effects of antiretroviral
      drugs (OR: 0.30; 95% CI: 0.14-0.67) were independently associated with
      willingness to accept PrEP. CONCLUSIONS: The awareness of PrEP in the MSM
      population was low. Sexual behavioral characteristics and knowledge about ART
      drugs may have effects on willingness to accept PrEP. Comprehensive prevention
      strategies should be recommended in the MSM community.

PMID- 22479321
TI  - Therapeutic hemoglobin levels after gene transfer in beta-thalassemia mice and in
      hematopoietic cells of beta-thalassemia and sickle cells disease patients.
AB  - Preclinical and clinical studies demonstrate the feasibility of treating beta
      thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the
      human beta-globin gene. However, previous studies have not addressed whether the
      ability of lentiviral vectors to increase hemoglobin synthesis might vary in
      different patients.We generated lentiviral vectors carrying the human beta-globin
      gene with and without an ankyrin insulator and compared their ability to induce
      hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of
      an ankyrin insulator leads to higher, potentially therapeutic levels of human
      beta-globin through a novel mechanism that links the rate of transcription of the
      transgenic beta-globin mRNA during erythroid differentiation with polysomal
      binding and efficient translation, as reported here for the first time. We also
      established a preclinical assay to test the ability of this novel vector to
      synthesize adult hemoglobin in erythroid precursors and in CD34(+) cells isolated
      from patients affected by beta-thalassemia and SCD. Among the thalassemic
      patients, we identified a subset of specimens in which hemoglobin production can
      be achieved using fewer copies of the vector integrated than in others. In SCD
      specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing
      adult hemoglobin (Hb A) and concurrently reducing the sickling tetramer (Hb
      S).Our results suggest two major findings. First, we discovered that for the
      purpose of expressing the beta-globin gene the ankyrin element is particularly
      suitable. Second, our analysis of a large group of specimens from beta
      thalassemic and SCD patients indicates that clinical trials could benefit from a
      simple test to predict the relationship between the number of vector copies
      integrated and the total amount of hemoglobin produced in the erythroid cells of
      prospective patients. This approach would provide vital information to select the
      best candidates for these clinical trials, before patients undergo myeloablation
      and bone marrow transplant.

PMID- 22479322
TI  - Pregnancy close to the edge: an immunosuppressive infiltrate in the chorionic
      plate of placentas from uncomplicated egg cell donation.
AB  - In pregnancies achieved after egg donation (ED) tolerance towards a completely
      allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of
      which numerous aspects are still unknown. A distinct lesion not described
      previously in the literature, was repeatedly found in the chorionic plate in a
      substantial portion of placentas from ED pregnancies, but never in placentas from
      normal term pregnancies. The aim of this study was to assess its origin and its
      cellular composition. The relation between the lesion, the clinical and
      histological parameters were assessed. In addition we investigated the relation
      with the number of HLA-mismatches and KIR genotype of mother and child.In ten out
      of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was
      present in the chorionic plate. A significantly lower incidence of pre-eclampsia
      was found in the group with the lesion; 0% versus 45.5%. A significant relation
      was found between this lesion and the presence of intervillositis, chronic
      deciduitis, presence of plasma cells and fibrin deposition in the decidua.
      Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the
      majority of cells present in the lesion are of maternal origin. The expression of
      the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was
      significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was
      significantly higher in cases with a lesion compared to the group without the
      lesion. In conclusion, a striking relationship was observed between the presence
      of a not previously described inflammatory lesion in the chorionic plate and the
      absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly
      maternal cells with a higher expression of the macrophage marker CD14+ and the M2
      marker CD163+. These findings suggest a protective immune mechanism which might
      contribute to the prevention of severe clinical complications like pre-eclampsia.

PMID- 22479323
TI  - Mitochondrial division/mitophagy inhibitor (Mdivi) ameliorates pressure overload
      induced heart failure.
AB  - BACKGROUND: We have previously reported the role of anti-angiogenic factors in
      inducing the transition from compensatory cardiac hypertrophy to heart failure
      and the significance of MMP-9 and TIMP-3 in promoting this process during
      pressure overload hemodynamic stress. Several studies reported the evidence of
      cardiac autophagy, involving removal of cellular organelles like mitochondria
      (mitophagy), peroxisomes etc., in the pathogenesis of heart failure. However,
      little is known regarding the therapeutic role of mitochondrial division
      inhibitor (Mdivi) in the pressure overload induced heart failure. We hypothesize
      that treatment with mitochondrial division inhibitor (Mdivi) inhibits abnormal
      mitophagy in a pressure overload heart and thus ameliorates heart failure
      condition. MATERIALS AND METHODS: To verify this, ascending aortic banding was
      done in wild type mice to create pressure overload induced heart failure and then
      treated with Mdivi and compared with vehicle treated controls. RESULTS:
      Expression of MMP-2, vascular endothelial growth factor, CD31, was increased,
      while expression of anti angiogenic factors like endostatin and angiostatin along
      with MMP-9, TIMP-3 was reduced in Mdivi treated AB 8 weeks mice compared to
      vehicle treated controls. Expression of mitophagy markers like LC3 and p62 was
      decreased in Mdivi treated mice compared to controls. Cardiac functional status
      assessed by echocardiography showed improvement and there is also a decrease in
      the deposition of fibrosis in Mdivi treated mice compared to controls.
      CONCLUSION: Above results suggest that Mdivi inhibits the abnormal cardiac
      mitophagy response during sustained pressure overload stress and propose the
      novel therapeutic role of Mdivi in ameliorating heart failure.

PMID- 22479324
TI  - Characterization of full-length enterovirus 71 strains from severe and mild
      disease patients in northeastern China.
AB  - Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has
      been a leading cause of childhood infection in China since 2008. Epidemic and
      molecular characteristics of HFMD have been examined in many areas of China,
      including the central and southern regions. However, clinical and genetic
      characterization of EV71 in the northeastern region of China is scarce. In this
      study, a series of analyses were performed on seven full-length EV71 sequences
      from HFMD patients who had either severe or mild disease. We have determined that
      these seven circulating EV71 viruses from Changchun, China are actually complex
      recombinant viruses involving multiple type A human enterovirus (HEV). Classified
      as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic
      recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the
      structural protein region (P1) of these viruses resembled that of the prototype
      EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high
      degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5'UTR
      had unclassified recombination,while partial 3D region of these viruses showed a
      high degree of similarity to CA16. Phylogenetic analysis of full-length or
      partial sequences of isolates from severe or mild disease patients in Changchun
      always formed a single cluster in various phylogenetic analyses of different
      genomic regions, suggesting that all seven strains originated from one single
      common ancestor. There was no correlation between viral genomic sequence and
      virulence. Thus, we found that circulating recombinant forms of EV71 are
      prevalent among HFMD patients in Northeastern China. The existence of a unique
      cluster of EV71 related viruses in Northeast China has important implications for
      vaccine development that would address the increasing prevalence of HFMD.

PMID- 22479325
TI  - Phylogeny and taxonomy of the round-eared sengis or elephant-shrews, genus
      Macroscelides (Mammalia, Afrotheria, Macroscelidea).
AB  - The round-eared sengis or elephant-shrews (genus Macroscelides) exhibit striking
      pelage variation throughout their ranges. Over ten taxonomic names have been
      proposed to describe this variation, but currently only two taxa are recognized
      (M. proboscideus proboscideus and M. p. flavicaudatus). Here, we review the
      taxonomic history of Macroscelides, and we use data on the geographic
      distribution, morphology, and mitochondrial DNA sequence to evaluate the current
      taxonomy. Our data support only two taxa that correspond to the currently
      recognized subspecies M. p. proboscideus and M. p. flavicaudatus. Mitochondrial
      haplotypes of these two taxa are reciprocally monophyletic with over 13%
      uncorrected sequence divergence between them. PCA analysis of 14 morphological
      characters (mostly cranial) grouped the two taxa into non-overlapping clusters,
      and body mass alone is a relatively reliable distinguishing character throughout
      much of Macroscelides range. Although fieldworkers were unable to find sympatric
      populations, the two taxa were found within 50 km of each other, and genetic
      analysis showed no evidence of gene flow. Based upon corroborating genetic data,
      morphological data, near sympatry with no evidence of gene flow, and differences
      in habitat use, we elevate these two forms to full species.

PMID- 22479326
TI  - Neuroticism modifies psychophysiological responses to fearful films.
AB  - BACKGROUND: Neuroticism is a personality component frequently found in anxious
      and depressive psychiatric disorders. The influence of neuroticism on negative
      emotions could be due to its action on stimuli related to fear and sadness, but
      this remains debated. Our goal was thus to better understand the impact of
      neuroticism through verbal and physiological assessment in response to stimuli
      inducing fear and sadness as compared to another negative emotion (disgust).
      METHODS: Fifteen low neurotic and 18 high neurotic subjects were assessed on an
      emotional attending task by using film excerpts inducing fear, disgust, and
      sadness. We recorded skin conductance response (SCR) and corrugator muscle
      activity (frowning) as indices of emotional expression. RESULTS: SCR was larger
      in high neurotic subjects than in low neurotics for fear relative to sadness and
      disgust. Moreover, corrugator activity and SCR were larger in high than in low
      neurotic subjects when fear was induced. CONCLUSION: After decades of evidence
      that individuals higher in neuroticism experience more intense emotional
      reactions to even minor stressors, our results indicate that they show greater
      SCR and expressive reactivity specifically to stimuli evoking fear rather than to
      those inducing sadness or disgust. Fear processing seems mainly under the
      influence of neuroticism. This modulation of autonomic activity by neurotics in
      response to threat/fear may explain their increased vulnerability to anxious
      psychopathologies such as PTSD (post traumatic stress disorder).

PMID- 22479327
TI  - Comparison of bone and renal effects in HIV-infected adults switching to abacavir
      or tenofovir based therapy in a randomized trial.
AB  - INTRODUCTION: Our objective was to compare the bone and renal effects among HIV
      infected patients randomized to abacavir or tenofovir-based combination anti
      retroviral therapy. METHODS: In an open-label randomized trial, HIV-infected
      patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to
      abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured
      bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin,
      procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I
      collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed
      renal function by estimated creatinine clearance, plasma cystatin C, and urinary
      levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated
      lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers
      were compared across study arms. RESULTS: Of 40 included patients, 35 completed
      48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27
      patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated
      patients we observed significant reductions from baseline in hip and lumbar spine
      BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was
      stable in patients in the ABC/3TC arm. The changes from baseline in BMD were
      significantly different between study arms. All bone turnover biomarkers except
      osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but
      early changes did not predict subsequent loss of BMD. Renal function parameters
      were similar between study arms although a small increase in NGAL was detected
      among TDF-treated patients. CONCLUSION: Switching to TDF/FTC-based therapy led to
      decreases in BMD and increases in bone turnover markers compared with ABC/3TC
      based treatment. No major difference in renal function was observed. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT00647244.

PMID- 22479328
TI  - Role of gonadotropin regulated testicular RNA helicase (GRTH/Ddx25) on polysomal
      associated mRNAs in mouse testis.
AB  - Gonadotropin Regulated Testicular RNA Helicase (GRTH/Ddx25) is a testis-specific
      multifunctional RNA helicase and an essential post-transcriptional regulator of
      spermatogenesis. GRTH transports relevant mRNAs from nucleus to cytoplasmic sites
      of meiotic and haploid germ cells and associates with actively translating
      polyribosomes. It is also a negative regulator of steroidogenesis in Leydig
      cells. To obtain a genome-wide perspective of GRTH regulated genes, in
      particularly those associated with polyribosomes, microarray differential gene
      expression analysis was performed using polysome-bound RNA isolated from testes
      of wild type (WT) and GRTH KO mice. 792 genes among the entire mouse genome were
      found to be polysomal GRTH-linked in WT. Among these 186 were down-regulated and
      7 up-regulated genes in GRTH null mice. A similar analysis was performed using
      total RNA extracted from purified germ cell populations to address GRTH action in
      individual target cells. The down-regulation of known genes concerned with
      spermatogenesis at polysomal sites in GRTH KO and their association with GRTH in
      WT coupled with early findings of minor or unchanged total mRNAs and abolition of
      their protein expression in KO underscore the relevance of GRTH in translation.
      Ingenuity pathway analysis predicted association of GRTH bound polysome genes
      with the ubiquitin-proteasome-heat shock protein signaling network pathway and
      NFkappaB/TP53/TGFB1 signaling networks were derived from the differentially
      expressed gene analysis. This study has revealed known and unexplored factors in
      the genome and regulatory pathways underlying GRTH action in male reproduction.

PMID- 22479329
TI  - Screening of MAMLD1 mutations in 70 children with 46,XY DSD: identification and
      functional analysis of two new mutations.
AB  - More than 50% of children with severe 46,XY disorders of sex development (DSD) do
      not have a definitive etiological diagnosis. Besides gonadal dysgenesis, defects
      in androgen biosynthesis, and abnormalities in androgen sensitivity, the
      Mastermind-like domain containing 1 (MAMLD1) gene, which was identified as
      critical for the development of male genitalia, may be implicated. The present
      study investigated whether MAMLD1 is implicated in cases of severe 46,XY DSD and
      whether routine sequencing of MAMLD1 should be performed in these
      patients.Seventy children with severe non-syndromic 46,XY DSD of unknown etiology
      were studied. One hundred and fifty healthy individuals were included as
      controls. Direct sequencing of the MAMLD1, AR, SRD5A2 and NR5A1 genes was
      performed. The transactivation function of the variant MAMLD1 proteins was
      quantified by the luciferase method.TWO NEW MUTATIONS WERE IDENTIFIED: p.S143X
      (c.428C>A) in a patient with scrotal hypospadias with microphallus and p.P384L
      (c.1151C>T) in a patient with penile hypospadias with microphallus. The in vitro
      functional study confirmed no residual transactivating function of the p.S143X
      mutant and a significantly reduced transactivation function of the p.P384L
      protein (p = 0.0032). The p.P359S, p.N662S and p.H347Q variants are also reported
      with particularly high frequency of the p.359T- p.662G haplotype in the DSD
      patients.Severe undervirilization in XY newborns can reveal mutations of MAMLD1.
      MAMLD1 should be routinely sequenced in these patients with otherwise normal AR,
      SRD5A2 and NR5A1genes.

PMID- 22479330
TI  - Correlation of diffusion and metabolic alterations in different clinical forms of
      multiple sclerosis.
AB  - Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide
      greater sensitivity than conventional MRI to detect diffuse alterations in normal
      appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different
      clinical forms. Therefore, the goal of this study is to combine DTI and MRSI
      measurements to analyze the relation between diffusion and metabolic markers, T2
      weighted lesion load (T2-LL) and the patients clinical status. The sensitivity
      and specificity of both methods were then compared in terms of MS clinical forms
      differentiation. MR examination was performed on 71 MS patients (27 relapsing
      remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP))
      and 24 control subjects. DTI and MRSI measurements were obtained from two
      identical regions of interest selected in left and right centrum semioval (CSO)
      WM. DTI metrics and metabolic contents were significantly altered in MS patients
      with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR
      patients. Significant correlations were observed between diffusion and metabolic
      measures to various degrees in every MS patients group. Most DTI metrics were
      significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in
      RR patients. A comparison analysis of MR methods efficiency demonstrated a better
      sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could
      distinguish all MS and SP patients groups from controls, while NAA/Cho ratio
      differentiated PP patients from controls. This study demonstrated that
      diffusivity changes related to microstructural alterations were correlated with
      metabolic changes and provided a better sensitivity to detect early changes,
      particularly in RR patients who are more subject to inflammatory processes. In
      contrast, the better specificity of metabolic ratios to detect axonal damage and
      demyelination may provide a better index for identification of PP patients.

PMID- 22479331
TI  - Comparison of in vitro- and chorioallantoic membrane (CAM)-culture systems for
      cryopreserved medulla-contained human ovarian tissue.
AB  - At present, there are three ways to determine effectively the quality of the
      cryopreservation procedure using ovarian tissue before the re-implantation
      treatment: evaluation of follicles after post-thawing xenotransplantation to SCID
      mouse, in-vitro culture in a large volume of culture medium under constant
      agitation and culture on embryonic chorio-allantoic membrane within a hen's eggs.
      The aim of this study was to compare the two methods, culture in vitro and
      culture on embryonic chorioallantoic membrane (CAM) of cryopreserved human
      ovarian medulla-contained and medulla-free cortex. Ovarian fragments were divided
      into small pieces (1.5-2.0*1.0-1.2*0.8-1.5) of two types, cortex with medulla and
      medulla-free cortex, frozen, thawed and randomly divided into the following four
      groups. Group 1: medulla-free cortex cultured in vitro for 8 days in large volume
      of medium with mechanical agitation, Group 2: medulla-containing cortex cultured
      in vitro, Group 3: medulla-free cortex cultured in CAM-system for 5 days, Group
      4: medulla-containing cortex cultured in CAM-system. The efficacy of the tissue
      culture was evaluated by the development of follicles and by intensiveness of
      angiogenesis in the tissue (von Willebrand factor and Desmin). For Group 1, 2, 3
      and 4, respectively 85%, 85%, 87% and 84% of the follicles were morphologically
      normal (P>0.1). The immunohistochemical analysis showed that angiogenesis
      detected by von Willebrand factor was lower in groups 1 and 3 (medulla-free
      cortex). Neo-vascularisation (by Desmin) was observed only in ovarian tissue of
      Group 4 (medulla-contained cortex after CAM-culture). It appears that the
      presence of medulla in ovarian pieces is beneficial for post-thaw development of
      cryopreserved human ovarian tissue. For medical practice it is recommended for
      evaluation of post-warming ovarian tissue to use the CAM-system as a valuable
      alternative to xenotransplantation and for cryopreservation of these tissues to
      prepare ovarian medulla-contained strips.

PMID- 22479332
TI  - Development of an in vitro model for the multi-parametric quantification of the
      cellular interactions between Candida yeasts and phagocytes.
AB  - We developed a new in vitro model for a multi-parameter characterization of the
      time course interaction of Candida fungal cells with J774 murine macrophages and
      human neutrophils, based on the use of combined microscopy, fluorometry, flow
      cytometry and viability assays. Using fluorochromes specific to phagocytes and
      yeasts, we could accurately quantify various parameters simultaneously in a
      single infection experiment: at the individual cell level, we measured the
      association of phagocytes to fungal cells and phagocyte survival, and monitored
      in parallel the overall phagocytosis process by measuring the part of ingested
      fungal cells among the total fungal biomass that changed over time. Candida
      albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they
      exhibited species-specific differences in their association rate with phagocytes.
      The fungal biomass uptaken by the phagocytes differed significantly according to
      the Candida species. The measure of the survival of fungal and immune cells
      during the interaction showed that C. albicans was the more aggressive yeast in
      vitro, destroying the vast majority of the phagocytes within five hours. All
      three species of Candida were able to survive and to escape macrophage
      phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C.
      albicans) and the fungal cell multiplication until phagocytes burst (C. glabrata,
      C. lusitaniae), or by the avoidance of phagocytosis (C. lusitaniae). We
      demonstrated that our model was sensitive enough to quantify small variations of
      the parameters of the interaction. The method has been conceived to be amenable
      to the high-throughput screening of mutants in order to unravel the molecular
      mechanisms involved in the interaction between yeasts and host phagocytes.

PMID- 22479333
TI  - Genomic organization, tissue distribution and functional characterization of the
      rat Pate gene cluster.
AB  - The cysteine rich prostate and testis expressed (Pate) proteins identified till
      date are thought to resemble the three fingered protein/urokinase-type
      plasminogen activator receptor proteins. In this study, for the first time, we
      report the identification, cloning and characterization of rat Pate gene cluster
      and also determine the expression pattern. The rat Pate genes are clustered on
      chromosome 8 and their predicted proteins retained the ten cysteine signature
      characteristic to TFP/Ly-6 protein family. PATE and PATE-F three dimensional
      protein structure was found to be similar to that of the toxin bucandin. Though
      Pate gene expression is thought to be prostate and testis specific, we observed
      that rat Pate genes are also expressed in seminal vesicle and epididymis and in
      tissues beyond the male reproductive tract. In the developing rats (20-60 day
      old), expression of Pate genes seem to be androgen dependent in the epididymis
      and testis. In the adult rat, androgen ablation resulted in down regulation of
      the majority of Pate genes in the epididymides. PATE and PATE-F proteins were
      found to be expressed abundantly in the male reproductive tract of rats and on
      the sperm. Recombinant PATE protein exhibited potent antibacterial activity,
      whereas PATE-F did not exhibit any antibacterial activity. Pate expression was
      induced in the epididymides when challenged with LPS. Based on our results, we
      conclude that rat PATE proteins may contribute to the reproductive and defense
      functions.

PMID- 22479334
TI  - Protease activity increases in plasma, peritoneal fluid, and vital organs after
      hemorrhagic shock in rats.
AB  - Hemorrhagic shock (HS) is associated with high mortality. A severe decrease in
      blood pressure causes the intestine, a major site of digestive enzymes, to become
      permeable - possibly releasing those enzymes into the circulation and peritoneal
      space, where they may in turn activate other enzymes, e.g. matrix
      metalloproteinases (MMPs). If uncontrolled, these enzymes may result in
      pathophysiologic cleavage of receptors or plasma proteins. Our first objective
      was to determine, in compartments outside of the intestine (plasma, peritoneal
      fluid, brain, heart, liver, and lung) protease activities and select protease
      concentrations after hemorrhagic shock (2 hours ischemia, 2 hours reperfusion).
      Our second objective was to determine whether inhibition of proteases in the
      intestinal lumen with a serine protease inhibitor (ANGD), a process that improves
      survival after shock in rats, reduces the protease activities distant from the
      intestine. To determine the protease activity, plasma and peritoneal fluid were
      incubated with small peptide substrates for trypsin-, chymotrypsin-, and elastase
      like activities or with casein, a substrate cleaved by multiple proteases.
      Gelatinase activities were determined by gelatin gel zymography and a specific
      MMP-9 substrate. Immunoblotting was used to confirm elevated pancreatic trypsin
      in plasma, peritoneal fluid, and lung and MMP-9 concentrations in all samples
      after hemorrhagic shock. Caseinolytic, trypsin-, chymotrypsin-, elastase-like,
      and MMP-9 activities were all significantly (p<0.05) upregulated after
      hemorrhagic shock regardless of enteral pretreatment with ANGD. Pancreatic
      trypsin was detected by immunoblot in the plasma, peritoneal space, and lungs
      after hemorrhagic shock. MMP-9 concentrations and activities were significantly
      upregulated after hemorrhagic shock in plasma, peritoneal fluid, heart, liver,
      and lung. These results indicate that protease activities, including that of
      trypsin, increase in sites distant from the intestine after hemorrhagic shock.
      Proteases, including pancreatic proteases, may be shock mediators and potential
      targets for therapy in shock.

PMID- 22479335
TI  - Designing adverse event forms for real-world reporting: participatory research in
      Uganda.
AB  - The wide-scale roll-out of artemisinin combination therapies (ACTs) for the
      treatment of malaria should be accompanied by continued surveillance of their
      safety. Post-marketing pharmacovigilance (PV) relies on adverse event (AE)
      reporting by clinicians, but as a large proportion of treatments are provided by
      non-clinicians in low-resource settings, the effectiveness of such PV systems is
      limited. To facilitate reporting, AE forms should be easily completed; however,
      most are challenging for lower-level health workers and non-clinicians to
      complete. Through participatory research, we sought to develop user-friendly AE
      report forms to capture information on events associated with ACTs.Following
      situation analysis, we undertook workshops with community medicine distributors
      and health workers in Jinja, Uganda, to develop a reporting form based on
      experiences and needs of users, and communication and visual perception
      principles. Participants gave feedback for revisions of subsequent versions. We
      then conducted 8 pretesting sessions with 77 potential end users to test and
      refine passive and active versions of the form.The development process resulted
      in a form that included a pictorial storyboard to communicate the rationale for
      the information needed and facilitate rapport between the reporter and the
      respondent, and a diary format to record the drug administration and event
      details in chronological relation to each other. Successive rounds of pretesting
      used qualitative and quantitative feedback to refine the form, with the final
      round showing over 80% of the form completed correctly by potential end users.We
      developed novel AE report forms that can be used by non-clinicians to capture
      pharmacovigilance data for anti-malarial drugs. The participatory approach was
      effective for developing forms that are intuitive for reporters, and motivating
      for respondents. The forms, or their key components, could be adapted for use in
      other low-literacy settings to improve quality and quantity of drug safety
      reports as new medicines are scaled-up.

PMID- 22479336
TI  - Carnivore translocations and conservation: insights from population models and
      field data for fishers (Martes pennanti).
AB  - Translocations are frequently used to restore extirpated carnivore populations.
      Understanding the factors that influence translocation success is important
      because carnivore translocations can be time consuming, expensive, and
      controversial. Using population viability software, we modeled reintroductions of
      the fisher, a candidate for endangered or threatened status in the Pacific states
      of the US. Our model predicts that the most important factor influencing
      successful re-establishment of a fisher population is the number of adult females
      reintroduced (provided some males are also released). Data from 38 translocations
      of fishers in North America, including 30 reintroductions, 5 augmentations and 3
      introductions, show that the number of females released was, indeed, a good
      predictor of success but that the number of males released, geographic region and
      proximity of the source population to the release site were also important
      predictors. The contradiction between model and data regarding males may relate
      to the assumption in the model that all males are equally good breeders. We
      hypothesize that many males may need to be released to insure a sufficient number
      of good breeders are included, probably large males. Seventy-seven percent of
      reintroductions with known outcomes (success or failure) succeeded; all 5
      augmentations succeeded; but none of the 3 introductions succeeded.
      Reintroductions were instrumental in reestablishing fisher populations within
      their historical range and expanding the range from its most-contracted state
      (43% of the historical range) to its current state (68% of the historical range).
      To increase the likelihood of translocation success, we recommend that managers:
      1) release as many fishers as possible, 2) release more females than males (55
      60% females) when possible, 3) release as many adults as possible, especially
      large males, 4) release fishers from a nearby source population, 5) conduct a
      formal feasibility assessment, and 6) develop a comprehensive implementation plan
      that includes an active monitoring program.

PMID- 22479337
TI  - Why do species co-occur? A test of alternative hypotheses describing abiotic
      differences in sympatry versus allopatry using spadefoot toads.
AB  - Areas of co-occurrence between two species (sympatry) are often thought to arise
      in regions where abiotic conditions are conducive to both species and are
      therefore intermediate between regions where either species occurs alone
      (allopatry). Depending on historical factors or interactions between species,
      however, sympatry might not differ from allopatry, or, alternatively, sympatry
      might actually be more extreme in abiotic conditions relative to allopatry. Here,
      we evaluate these three hypothesized patterns for how sympatry compares to
      allopatry in abiotic conditions. We use two species of congeneric spadefoot
      toads, Spea multiplicata and S. bombifrons, as our study system. To test these
      hypotheses, we created ecological niche models (specifically using Maxent) for
      both species to create a map of the joint probability of occurrence of both
      species. Using the results of these models, we identified three types of
      locations: two where either species was predicted to occur alone (i.e., allopatry
      for S. multiplicata and allopatry for S. bombifrons) and one where both species
      were predicted to co-occur (i.e., sympatry). We then compared the abiotic
      environment between these three location types and found that sympatry was
      significantly hotter and drier than the allopatric regions. Thus, sympatry was
      not intermediate between the alternative allopatric sites. Instead, sympatry
      occurred at one extreme of the conditions occupied by both species. We
      hypothesize that biotic interactions in these extreme environments facilitate co
      occurrence. Specifically, hybridization between S. bombifrons females and S.
      multiplicata males may facilitate co-occurrence by decreasing development time of
      tadpoles. Additionally, the presence of alternative food resources in more
      extreme conditions may preclude competitive exclusion of one species by the
      other. This work has implications for predicting how interacting species will
      respond to climate change, because species interactions may facilitate survival
      in extreme habitats.

PMID- 22479338
TI  - Priming with a recombinant pantothenate auxotroph of Mycobacterium bovis BCG and
      boosting with MVA elicits HIV-1 Gag specific CD8+ T cells.
AB  - A safe and effective HIV vaccine is required to significantly reduce the number
      of people becoming infected with HIV each year. In this study wild type
      Mycobacterium bovis BCG Pasteur and an attenuated pantothenate auxotroph strain
      (BCGDeltapanCD) that is safe in SCID mice, have been compared as vaccine vectors
      for HIV-1 subtype C Gag. Genetically stable vaccines BCG[pHS400] (BCG-Gag) and
      BCGDeltapanCD[pHS400] (BCGpan-Gag) were generated using the Pasteur strain of
      BCG, and a panothenate auxotroph of Pasteur respectively. Stability was achieved
      by the use of a codon optimised gag gene and deletion of the hsp60-lysA promoter
      gene cassette from the episomal vector pCB119. In this vector expression of gag
      is driven by the mtrA promoter and the Gag protein is fused to the Mycobacterium
      tuberculosis 19 kDa signal sequence. Both BCG-Gag and BCGpan-Gag primed the
      immune system of BALB/c mice for a boost with a recombinant modified vaccinia
      virus Ankara expressing Gag (MVA-Gag). After the boost high frequencies of
      predominantly Gag-specific CD8(+) T cells were detected when BCGpan-Gag was the
      prime in contrast to induction of predominantly Gag-specific CD4(+) T cells when
      priming with BCG-Gag. The differing Gag-specific T-cell phenotype elicited by the
      prime-boost regimens may be related to the reduced inflammation observed with the
      pantothenate auxotroph strain compared to the parent strain. These features make
      BCGpan-Gag a more desirable HIV vaccine candidate than BCG-Gag. Although no Gag
      specific cells could be detected after vaccination of BALB/c mice with either
      recombinant BCG vaccine alone, BCGpan-Gag protected mice against a surrogate
      vaccinia virus challenge.

PMID- 22479339
TI  - The naturally occurring YMDD mutation among patients chronically infected HBV and
      untreated with lamivudine: a systematic review and meta-analysis.
AB  - BACKGROUND: Several recent reports have demonstrated that tyrosine (Y)-methionine
      (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally
      occur in chronic HBV patients without antiviral treatment such as lamivudine
      therapy. This paper aims to assess the overall spontaneous incidence and related
      risk factors of YMDD-motif mutations among lamivudine-naive chronic HBV carriers,
      so as to provide some clue for clinical treatment of hepatitis B.
      METHODOLOGY/PRINCIPAL FINDINGS: Chinese and English literatures were searched for
      studies reporting natural YMDD mutations among untreated chronic HBV patients
      from 2001 to 2010. The incidence estimates were summarized and analyzed by meta
      analyses. Forty-seven eligible articles from eight countries were selected in
      this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif
      mutation among untreated chronic HBV patients from eight countries was 12.21%
      (95% CI: 9.69%-14.95%). China had an incidence of 13.38% (95% CI: 10.90%-16.07%)
      and seven other countries had an incidence of 9.90% (95% CI: 3.28%-19.55%),
      respectively. Lamivudine therapy would increase the risk of mutations 5.23 times
      higher than the untreated patients. A higher HBV DNA copy number was associated
      with increased incidence of natural YMDD mutation. No significant difference was
      found in YMDD mutation incidence between groups of different gender, age, HBeAg
      status, patients' ALT (alanine aminotransferase) level, and between the groups of
      HBV genotype B and C. CONCLUSIONS: The YMDD-motif mutations can occur
      spontaneously with a relatively high incidence in CHB patients untreated with
      lamivudine. These mutations might be the consequence of accumulated base mismatch
      due to the nature of viral polymerase. More fundamental and clinical studies are
      needed to clarify the influence of YMDD mutations in hepatitis B progression and
      antiviral treatment.

PMID- 22479340
TI  - Heat or insulation: behavioral titration of mouse preference for warmth or access
      to a nest.
AB  - In laboratories, mice are housed at 20-24 degrees C, which is below their lower
      critical temperature (~30 degrees C). This increased thermal stress has the
      potential to alter scientific outcomes. Nesting material should allow for
      improved behavioral thermoregulation and thus alleviate this thermal stress.
      Nesting behavior should change with temperature and material, and the choice
      between nesting or thermotaxis (movement in response to temperature) should also
      depend on the balance of these factors, such that mice titrate nesting material
      against temperature. Naive CD-1, BALB/c, and C57BL/6 mice (36 male and 36
      female/strain in groups of 3) were housed in a set of 2 connected cages, each
      maintained at a different temperature using a water bath. One cage in each set
      was 20 degrees C (Nesting cage; NC) while the other was one of 6 temperatures
      (Temperature cage; TC: 20, 23, 26, 29, 32, or 35 degrees C). The NC contained one
      of 6 nesting provisions (0, 2, 4, 6, 8, or 10g), changed daily. Food intake and
      nest scores were measured in both cages. As the difference in temperature between
      paired cages increased, feed consumption in NC increased. Nesting provision
      altered differences in nest scores between the 2 paired temperatures. Nest scores
      in NC increased with increasing provision. In addition, temperature pairings
      altered the difference in nest scores with the smallest difference between
      locations at 26 degrees C and 29 degrees C. Mice transferred material from NC to
      TC but the likelihood of transfer decreased with increasing provision. Overall,
      mice of different strains and sexes prefer temperatures between 26-29 degrees C
      and the shift from thermotaxis to nest building is seen between 6 and 10 g of
      material. Our results suggest that under normal laboratory temperatures, mice
      should be provided with no less than 6 grams of nesting material, but up to 10
      grams may be needed to alleviate thermal distress under typical temperatures.

PMID- 22479341
TI  - Protein phosphatase 1 dephosphorylates profilin-1 at Ser-137.
AB  - Profilin-1 (PFN1) plays an important role in the control of actin dynamics, and
      could represent an important therapeutic target in several diseases. We
      previously identified PFN1 as a huntingtin aggregation inhibitor, and others have
      implicated it as a tumor-suppressor. Rho-associated kinase (ROCK) directly
      phosphorylates PFN1 at Ser-137 to prevent its binding to polyproline sequences.
      This negatively regulates its anti-aggregation activity. However, the phosphatase
      that dephosphorylates PFN1 at Ser-137, and thus activates it, is unknown. Using a
      phospho-specific antibody against Ser-137 of PFN1, we characterized PFN1
      dephosphorylation in cultured cells based on immunocytochemistry and a
      quantitative plate reader-based assay. Both okadaic acid and endothall increased
      pS137-PFN1 levels at concentrations more consistent with their known IC(50)s for
      protein phosphatase 1 (PP1) than protein phosphatase 2A (PP2A). Knockdown of the
      catalytic subunit of PP1 (PP1Calpha), but not PP2A (PP2ACalpha), increased pS137
      PFN1 levels. PP1Calpha binds PFN1 in cultured cells, and this interaction was
      increased by a phosphomimetic mutation of PFN1 at Ser-137 (S137D). Together,
      these data define PP1 as the principal phosphatase for Ser-137 of PFN1, and
      provide mechanistic insights into PFN1 regulation by phosphorylation.

PMID- 22479342
TI  - MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate
      cancer growth.
AB  - PURPOSE: Prostate cancer (PCa) is characterized by deregulated expression of
      several tumor suppressor or oncogenic miRNAs. The objective of this study was the
      identification and characterization of miR-let-7c as a potential tumor suppressor
      in PCa. EXPERIMENTAL DESIGN: Levels of expression of miR-let-7c were examined in
      human PCa cell lines and tissues using qRT-PCR and in situ hybridization. Let-7c
      was overexpressed or suppressed to assess the effects on the growth of human PCa
      cell lines. Lentiviral-mediated re-expression of let-7c was utilized to assess
      the effects on human PCa xenografts. RESULTS: We identified miR-let-7c as a
      potential tumor suppressor in PCa. Expression of let-7c is downregulated in
      castration-resistant prostate cancer (CRPC) cells. Overexpression of let-7c
      decreased while downregulation of let-7c increased cell proliferation,
      clonogenicity and anchorage-independent growth of PCa cells in vitro. Suppression
      of let-7c expression enhanced the ability of androgen-sensitive PCa cells to grow
      in androgen-deprived conditions in vitro. Reconstitution of Let-7c by lentiviral
      mediated intratumoral delivery significantly reduced tumor burden in xenografts
      of human PCa cells. Furthermore, let-7c expression is downregulated in clinical
      PCa specimens compared to their matched benign tissues, while the expression of
      Lin28, a master regulator of let-7 miRNA processing, is upregulated in clinical
      PCa specimens. CONCLUSIONS: These results demonstrate that microRNA let-7c is
      downregulated in PCa and functions as a tumor suppressor, and is a potential
      therapeutic target for PCa.

PMID- 22479343
TI  - The KAP evaluation of intervention on fall-induced injuries among elders in a
      safe community in Shanghai, China.
AB  - BACKGROUND: To evaluate the effect of an intervention on fall induced injuries of
      elderly people in a safe-community in Shanghai and to discuss an intervention
      model that is proper for the community to generalize. METHODOLOGY/PRINCIPAL
      FINDINGS: Five neighborhood areas in a Safe Community were purposively selected.
      All individuals aged 60 years or over in five neighborhoods were prospective
      participants. From randomly selected prospective households with elders, 2,889
      (pre intervention) and 3,021 (post intervention) elderly people were included in
      the study. Knowledge, Attitude and Practice Model (KAP) questionnaires were used
      at the pre- and post-intervention phase for fall-induced injury prevention in the
      community. Descriptive statistics and chi-square tests were used. After the
      intervention, knowledge about the prevention of fall-induced injuries increased,
      as did attitudes, beliefs and good behaviors for fall prevention. Behavior
      modification was most notable with many behavior items changing significantly (p
      value<0.0001). CONCLUSIONS/ SIGNIFICANCE: The integrated program for reducing
      fall-related injuries in the community was effective in improving fall prevention
      among the elderly, but the intervention still needs further improvement.

PMID- 22479344
TI  - Structural insights from binding poses of CCR2 and CCR5 with clinically important
      antagonists: a combined in silico study.
AB  - Chemokine receptors are G protein-coupled receptors that contain seven
      transmembrane domains. In particular, CCR2 and CCR5 and their ligands have been
      implicated in the pathophysiology of a number of diseases, including rheumatoid
      arthritis and multiple sclerosis. Based on their roles in disease, they have been
      attractive targets for the pharmaceutical industry, and furthermore, targeting
      both CCR2 and CCR5 can be a useful strategy. Owing to the importance of these
      receptors, information regarding the binding site is of prime importance.
      Structural studies have been hampered due to the lack of X-ray crystal
      structures, and templates with close homologs for comparative modeling. Most of
      the previous models were based on the bovine rhodopsin and beta2-adrenergic
      receptor. In this study, based on a closer homolog with higher resolution (CXCR4,
      PDB code: 3ODU 2.5 A), we constructed three-dimensional models. The main aim of
      this study was to provide relevant information on binding sites of these
      receptors. Molecular dynamics simulation was done to refine the homology models
      and PROCHECK results indicated that the models were reasonable. Here, binding
      poses were checked with some established inhibitors of high pharmaceutical
      importance against the modeled receptors. Analysis of interaction modes gave an
      integrated interpretation with detailed structural information. The binding poses
      confirmed that the acidic residues Glu291 (CCR2) and Glu283 (CCR5) are important,
      and we also found some additional residues. Comparisons of binding sites of
      CCR2/CCR5 were done sequentially and also by docking a potent dual antagonist.
      Our results can be a starting point for further structure-based drug design.

PMID- 22479345
TI  - Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110delta
      prevents chronic rejection of heart allografts.
AB  - Chronic rejection is the major cause of long-term heart allograft failure,
      characterized by tissue infiltration by recipient T cells with indirect
      allospecificity. Phosphoinositol-3-kinase p110delta is a key mediator of T cell
      receptor signaling, regulating both T cell activation and migration of primed T
      cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic
      or pharmacologic inactivation of PI3K p110delta on the development of chronic
      allograft rejection in a murine model in which HY-mismatched male hearts were
      transplanted into female recipients. We show that suppression of p110delta
      activity significantly attenuates the development of chronic rejection of heart
      grafts in the absence of any additional immunosuppressive treatment by impairing
      the localization of antigen-specific T cells to the grafts, while not inducing
      specific T cell tolerance. p110delta pharmacologic inactivation is effective when
      initiated after transplantation. Targeting p110delta activity might be a viable
      strategy for the treatment of heart chronic rejection in humans.

PMID- 22479346
TI  - Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as hypertension susceptibility
      genes in Han Chinese with a genome-wide gene-based association study.
AB  - Hypertension is a complex disorder with high prevalence rates all over the world.
      We conducted the first genome-wide gene-based association scan for hypertension
      in a Han Chinese population. By analyzing genome-wide single-nucleotide
      polymorphism data of 400 matched pairs of young-onset hypertensive patients and
      normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100
      susceptibility genes for hypertension were identified and also validated with
      permutation tests. Seventeen of the 100 genes exhibited differential allelic and
      expression distributions between patient and control groups. These genes provided
      a good molecular signature for classifying hypertensive patients and normotensive
      controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only
      identified by our gene-based association scan and gene expression analysis but
      were also replicated by a gene-based association analysis of the Hong Kong
      Hypertension Study. Moreover, cis-acting expression quantitative trait loci
      associated with the differentially expressed genes were found and linked to
      hypertension. IGF1, which encodes insulin-like growth factor 1, is associated
      with cardiovascular disorders, metabolic syndrome, decreased body weight/size,
      and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic
      sodium bicarbonate cotransporter 1, is associated with decreased body weight/size
      and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain
      containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1,
      which encodes the scm-like with four MBT domains protein 1, is a novel
      hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant
      differential allelic and expressed distributions between hypertensive patients
      and normotensive controls. GRB14 was also found relevant to blood pressure in a
      previous genetic association study in East Asian populations. TMEM56 and KIAA1797
      may be specific to Taiwanese populations, because they were not validated by the
      two replication studies. Identification of these genes enriches the collection of
      hypertension susceptibility genes, thereby shedding light on the etiology of
      hypertension in Han Chinese populations.

PMID- 22479347
TI  - Novel plasmids and resistance phenotypes in Yersinia pestis: unique plasmid
      inventory of strain Java 9 mediates high levels of arsenic resistance.
AB  - Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not
      restricted to the three classical virulence plasmids. The Java 9 strain of Y.
      pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although
      it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it
      retains virulence in mouse and non-human primate animal models. While comparing
      diverse Y. pestis strains using subtractive hybridization, we identified
      sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying
      the transposon Tn2502, which is known to encode arsenic resistance. Here we
      demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance
      mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic
      resistance was self-transmissible from Java 9 to other Y. pestis strains via
      conjugation. Genomic analysis of the atypical plasmid inventory of Java 9
      identified pCD and pPCP plasmids of atypical size and two previously
      uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance
      encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9
      are found on all four indigenous plasmids, including the two novel cryptic
      plasmids. This unique mobilome introduces more than 105 genes into the species
      gene pool. The majority of these are encoded by the two entirely novel self
      transmissible plasmids, which show partial homology and synteny to other
      enterics. In contrast to the reductive evolution in Y. pestis, this study
      underlines the major impact of a dynamic mobilome and lateral acquisition in the
      genome evolution of the plague bacterium.

PMID- 22479348
TI  - Chromatin composition is changed by poly(ADP-ribosyl)ation during chromatin
      immunoprecipitation.
AB  - Chromatin-immunoprecipitation (ChIP) employs generally a mild formaldehyde cross
      linking step, which is followed by isolation of specific protein-DNA complexes
      and subsequent PCR testing, to analyze DNA-protein interactions. Poly(ADP
      ribosyl)ation, a posttranslational modification involved in diverse cellular
      functions like repair, replication, transcription, and cell death regulation, is
      most prominent after DNA damage. Poly(ADP-ribose)polymerase-1 is activated upon
      binding to DNA strand-breaks and coordinates repair by recruitment or
      displacement of proteins. Several proteins involved in different nuclear pathways
      are directly modified or contain poly(ADP-ribose)-interaction motifs. Thus,
      poly(ADP-ribose) regulates chromatin composition. In immunofluorescence
      experiments, we noticed artificial polymer-formation after formaldehyde-fixation
      of undamaged cells. Therefore, we analyzed if the formaldehyde applied during
      ChIP also induces poly(ADP-ribosyl)ation and its impact on chromatin composition.
      We observed massive polymer-formation in three different ChIP-protocols tested
      independent on the cell line. This was due to induction of DNA damage signaling
      as monitored by gammaH2AX formation. To abrogate poly(ADP-ribose) synthesis, we
      inhibited this enzymatic reaction either pharmacologically or by increased
      formaldehyde concentration. Both approaches changed ChIP-efficiency.
      Additionally, we detected specific differences in promoter-occupancy of tested
      transcription factors as well as the in the presence of histone H1 at the
      respective sites. In summary, we show here that standard ChIP is flawed by
      artificial formation of poly(ADP-ribose) and suppression of this enzymatic
      activity improves ChIP-efficiency in general. Also, we detected specific changes
      in promoter-occupancy dependent on poly(ADP-ribose). By preventing polymer
      synthesis with the proposed modifications in standard ChIP protocols it is now
      possible to analyze the natural chromatin-composition.

PMID- 22479349
TI  - Estimating individual exposure to malaria using local prevalence of malaria
      infection in the field.
AB  - BACKGROUND: Heterogeneity in malaria exposure complicates survival analyses of
      vaccine efficacy trials and confounds the association between immune correlates
      of protection and malaria infection in longitudinal studies. Analysis may be
      facilitated by taking into account the variability in individual exposure levels,
      but it is unclear how exposure can be estimated at an individual level. METHOD
      AND FINDINGS: We studied three cohorts (Chonyi, Junju and Ngerenya) in Kilifi
      District, Kenya to assess measures of malaria exposure. Prospective data were
      available on malaria episodes, geospatial coordinates, proximity to infected and
      uninfected individuals and residence in predefined malaria hotspots for 2,425
      individuals. Antibody levels to the malaria antigens AMA1 and MSP1(142) were
      available for 291 children from Junju. We calculated distance-weighted local
      prevalence of malaria infection within 1 km radius as a marker of individual's
      malaria exposure. We used multivariable modified Poisson regression model to
      assess the discriminatory power of these markers for malaria infection (i.e.
      asymptomatic parasitaemia or clinical malaria). The area under the receiver
      operating characteristic (ROC) curve was used to assess the discriminatory power
      of the models. Local malaria prevalence within 1 km radius and AMA1 and MSP1(142)
      antibodies levels were independently associated with malaria infection. Weighted
      local malaria prevalence had an area under ROC curve of 0.72 (95%CI: 0.66-0.73),
      0.71 (95%CI: 0.69-0.73) and 0.82 (95%CI: 0.80-0.83) among cohorts in Chonyi,
      Junju and Ngerenya respectively. In a small subset of children from Junju, a
      model incorporating weighted local malaria prevalence with AMA1 and MSP1(142)
      antibody levels provided an AUC of 0.83 (95%CI: 0.79-0.88). CONCLUSION: We have
      proposed an approach to estimating the intensity of an individual's malaria
      exposure in the field. The weighted local malaria prevalence can be used as
      individual marker of malaria exposure in malaria vaccine trials and longitudinal
      studies of natural immunity to malaria.

PMID- 22479350
TI  - Confining domains lead to reaction bursts: reaction kinetics in the plasma
      membrane.
AB  - Confinement of molecules in specific small volumes and areas within a cell is
      likely to be a general strategy that is developed during evolution for regulating
      the interactions and functions of biomolecules. The cellular plasma membrane,
      which is the outermost membrane that surrounds the entire cell, was considered to
      be a continuous two-dimensional liquid, but it is becoming clear that it consists
      of numerous nano-meso-scale domains with various lifetimes, such as raft domains
      and cytoskeleton-induced compartments, and membrane molecules are dynamically
      trapped in these domains. In this article, we give a theoretical account on the
      effects of molecular confinement on reversible bimolecular reactions in a
      partitioned surface such as the plasma membrane. By performing simulations based
      on a lattice-based model of diffusion and reaction, we found that in the presence
      of membrane partitioning, bimolecular reactions that occur in each compartment
      proceed in bursts during which the reaction rate is sharply and briefly increased
      even though the asymptotic reaction rate remains the same. We characterized the
      time between reaction bursts and the burst amplitude as a function of the model
      parameters, and discussed the biological significance of the reaction bursts in
      the presence of strong inhibitor activity.

PMID- 22479351
TI  - Somatic integration of single ion channel responses of alpha7 nicotinic
      acetylcholine receptors enhanced by PNU-120596.
AB  - Positive allosteric modulators of highly Ca(2+)-permeable alpha7 nicotinic
      acetylcholine receptors, such as PNU-120596, may become useful therapeutic tools
      supporting neuronal survival and function. However, despite promising results,
      the initial optimism has been tempered by the concerns for cytotoxicity. The same
      concentration of a given nicotinic agent can be neuroprotective, ineffective or
      neurotoxic due to differences in the expression of alpha7 receptors and
      susceptibility to Ca(2+) influx among various subtypes of neurons. Resolution of
      these concerns may require an ability to reliably detect, evaluate and optimize
      the extent of alpha7 somatic ionic influx, a key determinant of the likelihood of
      neuronal survival and function. In the presence of PNU-120596 and physiological
      choline (~10 uM), the activity of individual alpha7 channels can be detected in
      whole-cell recordings as step-like current/voltage deviations. However, the
      extent of alpha7 somatic influx remains elusive because the activity of
      individual alpha7 channels may not be integrated across the entire soma, instead
      affecting only specific subdomains located in the channel vicinity. Such a
      compartmentalization may obstruct detection and integration of alpha7 currents,
      causing an underestimation of alpha7 activity. By contrast, if step-like alpha7
      currents are integrated across the soma, then a reliable quantification of alpha7
      influx in whole-cell recordings is possible and could provide a rational basis
      for optimization of conditions that support survival of alpha7-expressing
      neurons. This approach can be used to directly correlate alpha7 single-channel
      activity to neuronal function. In this study, somatic dual-patch recordings were
      conducted using large hypothalamic and hippocampal neurons in acute coronal rat
      brain slices. The results demonstrate that the membrane electrotonic properties
      do not impede somatic signaling, allowing reliable estimates of somatic ionic and
      Ca(2+) influx through alpha7 channels, while the somatic space-clamp error is
      minimal (~0.01 mV/um). These research efforts could benefit optimization of
      potential alpha7-PAM-based therapies.

PMID- 22479352
TI  - The role of inflammatory pathway genetic variation on maternal metabolic
      phenotypes during pregnancy.
AB  - BACKGROUND: Since mediators of inflammation are associated with insulin
      resistance, and the risk of developing diabetes mellitus and gestational
      diabetes, we hypothesized that genetic variation in members of the inflammatory
      gene pathway impact glucose levels and related phenotypes in pregnancy. We
      evaluated this hypothesis by testing for association between genetic variants in
      31 inflammatory pathway genes in the Hyperglycemia and Adverse Pregnancy Outcome
      (HAPO) cohort, a large multiethnic multicenter study designed to address the
      impact of glycemia less than overt diabetes on pregnancy outcome. RESULTS:
      Fasting, 1-hour, and 2-hour glucose, fasting and 1-hour C-peptide, and HbA1c
      levels were measured in blood samples obtained from HAPO participants during an
      oral glucose tolerance test at 24-32 weeks gestation. We tested for association
      between 458 SNPs mapping to 31 genes in the inflammatory pathway and metabolic
      phenotypes in 3836 European ancestry and 1713 Thai pregnant women. The strongest
      evidence for association was observed with TNF alpha and HbA1c (rs1052248; 0.04%
      increase per allele C; p-value = 4.4*10(-5)), RETN and fasting plasma glucose
      (rs1423096; 0.7 mg/dl decrease per allele A; p-value = 1.1*10(-4)), IL8 and 1 hr
      plasma glucose (rs2886920; 2.6 mg/dl decrease per allele T; p-value = 1.3*10(
      4)), ADIPOR2 and fasting C-peptide (rs2041139; 0.55 ug/L decrease per allele A; p
      value = 1.4*10(-4)), LEPR and 1-hour C-peptide (rs1171278; 0.62 ug/L decrease per
      allele T; p-value = 2.4*10(-4)), and IL6 and 1-hour plasma glucose (rs6954897; 
      2.29 mg/dl decrease per allele G, p-value = 4.3*10(-4)). CONCLUSIONS: Based on
      the genes surveyed in this study the inflammatory pathway is unlikely to have a
      strong impact on maternal metabolic phenotypes in pregnancy although variation in
      individual members of the pathway (e.g. RETN, IL8, ADIPOR2, LEPR, IL6, and TNF
      alpha,) may contribute to metabolic phenotypes in pregnant women.

PMID- 22479353
TI  - Inflammation aggravates disease severity in Marfan syndrome patients.
AB  - BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major
      features in cardiovascular, ocular and skeletal systems, associated with large
      clinical variability. Numerous studies reveal an involvement of TGF-beta
      signaling. However, the contribution of tissue inflammation is not addressed so
      far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and
      inflammation are up-regulated in patients with MFS. We analyzed transcriptome
      wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array
      and levels of TGF-beta and various cytokines in their plasma. Within our MFS
      population, increased plasma levels of TGF-beta were found especially in MFS
      patients with aortic root dilatation (124 pg/ml), when compared to MFS patients
      with normal aorta (10 pg/ml; p = 8*10(-6), 95% CI: 70-159 pg/ml). Interestingly,
      our microarray data show that increased expression of inflammatory genes was
      associated with major clinical features within the MFS patients group; namely
      severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for
      both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and
      HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal
      features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with
      progressive aortic disease had higher levels of Macrophage Colony Stimulating
      Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS
      aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02)
      and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS
      patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying
      role of inflammation in MFS. Inflammation might be a novel therapeutic target in
      these patients.

PMID- 22479354
TI  - Interferon-alpha regulates glutaminase 1 promoter through STAT1 phosphorylation:
      relevance to HIV-1 associated neurocognitive disorders.
AB  - HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1
      infection and affect up to 50% of infected individuals. Activated microglia and
      macrophages are critical cell populations that are involved in the pathogenesis
      of HAND, which is specifically related to the production and release of various
      soluble neurotoxic factors including glutamate. In the central nervous system
      (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme
      glutaminase. Our previous study has shown that glutaminase is upregulated in HIV
      1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1
      leads to glutaminase upregulation, or how glutaminase expression is regulated in
      general, remains unclear. In this study, using a dual-luciferase reporter assay
      system, we demonstrated that interferon (IFN) alpha specifically activated the
      glutaminase 1 (GLS1) promoter. Furthermore, IFN-alpha treatment increased signal
      transducer and activator of transcription 1 (STAT1) phosphorylation and
      glutaminase mRNA and protein levels. IFN-alpha stimulation of GLS1 promoter
      activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a
      chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to
      directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1
      phosphorylation and significantly enhanced by IFN-alpha treatment. More
      importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to
      the GLS1 promoter, which was associated with increased glutamate levels. The
      clinical relevance of these findings was further corroborated with investigation
      of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1) mRNA
      levels in HIV associated-dementia (HAD) individuals correlate with STAT1
      (p<0.01), IFN-alpha (p<0.05) and IFN-beta (p<0.01). Together, these data indicate
      that both HIV-1 infection and IFN-alpha treatment increase glutaminase expression
      through STAT1 phosphorylation and by binding to the GLS1 promoter. Since
      glutaminase is a potential component of elevated glutamate production during the
      pathogenesis of HAND, our data will help to identify additional therapeutic
      targets for the treatment of HAND.

PMID- 22479355
TI  - The study on newly developed McAb NJ001 specific to non-small cell lung cancer
      and its biological characteristics.
AB  - Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and
      immunotherapy. McAb-based immunotherapy that targets tumor antigens has had great
      achivement. In this study, a cell clone which kept secreting high-titer IgG1-type
      McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was
      obtained. The titer of purified NJ001 was 2*10(6). The antigen named SP70 of
      NSCLC specifically identified by NJ001 was proved to be a protein with the
      relative molecular mass (Mr) of 70 kDa. The results of immunohistochemical
      staining indicated that NJ001 could positively react to NSCLC, but weak
      positively or negatively react to human small-cell lung cancer (SCLC), pulmonary
      pseudotumor and other epithelial tumors. In soft agar assay, the colony formation
      efficiency in NJ001 groups decreased in a dose-dependent manner. For the
      concentration of 100 ug/ml, 200 ug/ml and 400 ug/ml, the inhibition ratio of
      colony formation was 23.4%, 62.5% and 100% respectively. Meanwhile, NJ001 caused
      significant reduction in tumor volume and tumor weight compared to control mice
      in lung cancer xenograft model. The tumor growth inhibition ratio in 200 ug, 400
      ug and 800 ug NJ001 groups was 10.44%, 37.29% and 44.04%, respectively. NJ001
      also led to cytomorphological changes and induced the apoptosis of human lung
      adenocarcinoma cell line SPC-A1 significantly. The newly developed NJ001
      selectively reacted to NSCLC and exhibited anti-tumor activity both in vitro and
      in vivo. NJ001 is of great value concerning immunodiagnostics and immunotherapy
      for NSCLC and holds promise for further research regarding the mechanism
      underlying tumor progression of NSCLC.

PMID- 22479356
TI  - A combined approach of high-throughput sequencing and degradome analysis reveals
      tissue specific expression of microRNAs and their targets in cucumber.
AB  - MicroRNAs (miRNAs) are endogenous small RNAs playing an important regulatory
      function in plant development and stress responses. Among them, some are
      evolutionally conserved in plant and others are only expressed in certain
      species, tissue or developmental stages. Cucumber is among the most important
      greenhouse species in the world, but only a limited number of miRNAs from
      cucumber have been identified and the experimental validation of the related
      miRNA targets is still lacking. In this study, two independent small RNA
      libraries from cucumber leaves and roots were constructed, respectively, and
      sequenced with the high-throughput Illumina Solexa system. Based on sequence
      similarity and hairpin structure prediction, a total of 29 known miRNA families
      and 2 novel miRNA families containing a total of 64 miRNA were identified. QRT
      PCR analysis revealed that some of the cucumber miRNAs were preferentially
      expressed in certain tissues. With the recently developed 'high throughput
      degradome sequencing' approach, 21 target mRNAs of known miRNAs were identified
      for the first time in cucumber. These targets were associated with development,
      reactive oxygen species scavenging, signaling transduction and transcriptional
      regulation. Our study provides an overview of miRNA expression profile and
      interaction between miRNA and target, which will help further understanding of
      the important roles of miRNAs in cucumber plants.

PMID- 22479357
TI  - Prevention and mitigation of acute radiation syndrome in mice by synthetic
      lipopeptide agonists of Toll-like receptor 2 (TLR2).
AB  - Bacterial lipoproteins (BLP) induce innate immune responses in mammals by
      activating heterodimeric receptor complexes containing Toll-like receptor 2
      (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-kappaB)-dependent
      upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which
      have been implicated in radiation protection. Here we demonstrate that synthetic
      lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal
      BLP significantly increase mouse survival following lethal total body irradiation
      (TBI) when administered between 48 hours before and 24 hours after irradiation.
      The TBI dose ranges against which sLP are effective indicate that sLP primarily
      impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP
      treatment accelerated recovery of bone marrow (BM) and spleen cellularity and
      ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of
      irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection
      requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2
      null BM on a wild type background, indicating that radioprotection of the HP
      system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP
      injection resulted in strong transient induction of multiple cytokines with known
      roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF),
      keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced
      cytokines, particularly G-CSF, are likely mediators of the
      radioprotective/mitigative activity of sLP. This study illustrates the strong
      potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in
      defense and medical scenarios.

PMID- 22479358
TI  - Composition and evolution of the vertebrate and mammalian selenoproteomes.
AB  - BACKGROUND: Selenium is an essential trace element in mammals due to its presence
      in proteins in the form of selenocysteine (Sec). Human genome codes for 25 Sec
      containing protein genes, and mouse and rat genomes for 24. METHODOLOGY/PRINCIPAL
      FINDINGS: We characterized the selenoproteomes of 44 sequenced vertebrates by
      applying gene prediction and phylogenetic reconstruction methods, supplemented
      with the analyses of gene structures, alternative splicing isoforms, untranslated
      regions, SECIS elements, and pseudogenes. In total, we detected 45 selenoprotein
      subfamilies. 28 of them were found in mammals, and 41 in bony fishes. We define
      the ancestral vertebrate (28 proteins) and mammalian (25 proteins)
      selenoproteomes, and describe how they evolved along lineages through gene
      duplication (20 events), gene loss (10 events) and replacement of Sec with
      cysteine (12 events). We show that an intronless selenophosphate synthetase 2
      gene evolved in early mammals and replaced functionally the original multiexon
      gene in placental mammals, whereas both genes remain in marsupials. Mammalian
      thioredoxin reductase 1 and thioredoxin-glutathione reductase evolved from an
      ancestral glutaredoxin-domain containing enzyme, still present in fish.
      Selenoprotein V and GPx6 evolved specifically in placental mammals from
      duplications of SelW and GPx3, respectively, and GPx6 lost Sec several times
      independently. Bony fishes were characterized by duplications of several
      selenoprotein families (GPx1, GPx3, GPx4, Dio3, MsrB1, SelJ, SelO, SelT, SelU1,
      and SelW2). Finally, we report identification of new isoforms for several
      selenoproteins and describe unusually conserved selenoprotein pseudogenes.
      CONCLUSIONS/SIGNIFICANCE: This analysis represents the first comprehensive survey
      of the vertebrate and mammal selenoproteomes, and depicts their evolution along
      lineages. It also provides a wealth of information on these selenoproteins and
      their forms.

PMID- 22479359
TI  - Microencapsulated 3-dimensional sensor for the measurement of oxygen in single
      isolated pancreatic islets.
AB  - BACKGROUND: Oxygen consumption reflects multiple processes in pancreatic islets
      including mechanisms contributing to insulin secretion, oxidative stress and
      viability, providing an important readout in studies of islet function, islet
      viability and drug testing. Due to the scarcity, heterogeneity, and intrinsic
      kinetic properties of individual islets, it would be of great benefit to detect
      oxygen consumption by single islets. We present a novel method we have developed
      to image oxygen in single islets. METHODOLOGY/PRINCIPAL FINDINGS: Using a
      microfluidics system, individual islets and a fluorescent oxygen-sensitive dye
      were encased within a thin alginate polymer layer. Insulin secretion by the
      encapsulated islets was normal. Fluorescent signal from the encased dye, detected
      using a standard inverted fluorescence microscope and digital camera, was stable
      and proportional to the amount of oxygen in the media. When integrated into a
      perifusion system, the sensing system detected changes in response to metabolic
      substrates, mitochondrial poisons, and induced-oscillations. Glucose responses
      averaged 30.1+/-7.1% of the response to a metabolic inhibitor (cyanide),
      increases were observed in all cases (n = 6), and the system was able to resolve
      changes in oxygen consumption that had a period greater than 0.5 minutes. The
      sensing system operated similarly from 2-48 hours following encapsulation, and
      viability and function of the islets were not significantly affected by the
      encapsulation process. CONCLUSIONS/SIGNIFICANCE: An oxygen-dependent dye situated
      around and within a pancreatic islet encapsulated by a thin layer of alginate was
      sensitive to changes in oxygen consumption, and was not harmful to the function
      or viability of islets over the course of two days. The microcapsule-based
      sensing method is particularly suited to assessing the effects of compounds (dose
      responses and time courses) and chronic changes occurring over the course of
      days. The approach should be applicable to other cell types and dyes sensitive to
      other biologically important molecules.

PMID- 22479360
TI  - Evaluation of indirect fluorescent antibody assays compared to rapid influenza
      diagnostic tests for the detection of pandemic influenza A (H1N1) pdm09.
AB  - Performance of indirect fluorescent antibody (IFA) assays and rapid influenza
      diagnostic tests (RIDT) during the 2009 H1N1 pandemic was evaluated, along with
      the relative effects of age and illness severity on test accuracy. Clinicians and
      laboratories submitted specimens on patients with respiratory illness to public
      health from April to mid October 2009 for polymerase chain reaction (PCR) testing
      as part of pandemic H1N1 surveillance efforts in Orange County, CA; IFA and RIDT
      were performed in clinical settings. Sensitivity and specificity for detection of
      the 2009 pandemic H1N1 strain, now officially named influenza A(H1N1)pdm09, were
      calculated for 638 specimens. Overall, approximately 30% of IFA tests and RIDTs
      tested by PCR were falsely negative (sensitivity 71% and 69%, respectively).
      Sensitivity of RIDT ranged from 45% to 84% depending on severity and age of
      patients. In hospitalized children, sensitivity of IFA (75%) was similar to RIDT
      (84%). Specificity of tests performed on hospitalized children was 94% for IFA
      and 80% for RIDT. Overall sensitivity of RIDT in this study was comparable to
      previously published studies on pandemic H1N1 influenza and sensitivity of IFA
      was similar to what has been reported in children for seasonal influenza. Both
      diagnostic tests produced a high number of false negatives and should not be used
      to rule out influenza infection.

PMID- 22479361
TI  - Efficacy of a high-dose in addition to daily low-dose vitamin A in children
      suffering from severe acute malnutrition with other illnesses.
AB  - BACKGROUND: Efficacy of high-dose vitamin A (VA) in children suffering from
      severe acute malnutrition (SAM) has recently been questioned. This study compared
      the efficacy of a single high-dose (200,000 IU) in addition to daily low-dose
      (5000 IU) VA in the management of children suffering from SAM with diarrhea
      and/or acute lower respiratory tract infection (ALRI). METHODS: In a randomized,
      double-blind, controlled clinical trial in icddr,b, Bangladesh during 2005-07,
      children aged 6-59 months with weight-for-height <-3 Z-score and/or bipedal edema
      (SAM) received either a high-dose VA or placebo on admission day. Both the groups
      received 5,000 IU/day VA in a multivitamins drop for 15 days and other standard
      treatment which is similar to WHO guidelines. RESULTS: A total 260 children (130
      in each group) were enrolled. All had diarrhea, 54% had concomitant ALRI, 50% had
      edema, 48.5% were girl with a mean+/-SD age of 16+/-10 months. None had clinical
      signs of VA deficiency. Mean+/-SD baseline serum retinol was 13.15+/-9.28 ug/dl,
      retinol binding protein was 1.27+/-0.95 mg/dl, and pre-albumin was 7.97+/-3.96
      mg/dl. Median (inter quartile range) of C-reactive protein was 7.8 (2.1, 22.2)
      mg/L. Children of the two groups did not differ in any baseline characteristic.
      Over the 15 days treatment period resolution of diarrhea, ALRI, edema,
      anthropometric changes, and biochemical indicators of VA were similar between the
      groups. The high-dose VA supplementation in children with SAM did not show any
      adverse event. CONCLUSIONS: Efficacy of daily low-dose VA compared to an
      additional single high-dose was not observed to be better in the management of
      children suffering from SAM with other acute illnesses. A single high-dose VA may
      be given especially where the children with SAM may leave the hospital/treatment
      center early. TRIAL REGISTRATION: ClinicalTrials.gov NCT00388921.

PMID- 22479362
TI  - The putative tumor suppressor VILIP-1 counteracts epidermal growth factor-induced
      epidermal-mesenchymal transition in squamous carcinoma cells.
AB  - Epithelial-mesenchymal transition (EMT) is a crucial step for the acquisition of
      invasive properties of carcinoma cells during tumor progression. Epidermal growth
      factor (EGF)-treatment of squamous cell carcinoma (SCC) cells provokes changes in
      the expression of lineage markers, morphological changes, and a higher invasive
      and metastatic potential. Here we show that chronic stimulation with EGF induces
      EMT in skin-derived SCC cell lines along with the down-regulation of the
      epithelial marker E-cadherin, and of the putative tumor suppressor VILIP-1
      (visinin-like protein 1). In esophageal squamous cell carcinoma and non-small
      cell lung carcinoma the loss of VILIP-1 correlates with clinicopathological
      features related to enhanced invasiveness. VILIP-1 has previously been shown to
      suppress tumor cell invasion via enhancing cAMP-signaling in a murine SCC model.
      In mouse skin SCC cell lines the VILIP-1-negative tumor cells have low cAMP
      levels, whereas VILIP-1-positive SCCs possess high cAMP levels, but low invasive
      properties. We show that in VILIP-1-negative SCCs, Snail1, a transcriptional
      repressor involved in EMT, is up-regulated. Snail1 expression is reduced by
      ectopic VILIP-1-expression in VILIP-1-negative SCC cells, and application of the
      general adenylyl cyclase inhibitor 2',3'-dideoxyadenosine attenuated this effect.
      Conversely, EGF-stimulation of VILIP-1-positive SCC cells leads to the down
      regulation of VILIP-1 and the induction of Snail1 expression. The induction of
      Snail is inhibited by elevated cAMP levels. The role of cAMP in EMT was further
      highlighted by its suppressive effect on the EGF-induced enhancement of migration
      in VILIP-1-positive SCC cells. These findings indicate that VILIP-1 is involved
      in EMT of SCC by regulating the transcription factor Snail1 in a cAMP-dependent
      manner.

PMID- 22479363
TI  - A cost-effectiveness analysis of "test" versus "treat" patients hospitalized with
      suspected influenza in Hong Kong.
AB  - BACKGROUND: Seasonal and 2009 H1N1 influenza viruses may cause severe diseases
      and result in excess hospitalization and mortality in the older and younger
      adults, respectively. Early antiviral treatment may improve clinical outcomes. We
      examined potential outcomes and costs of test-guided versus empirical treatment
      in patients hospitalized for suspected influenza in Hong Kong. METHODS: We
      designed a decision tree to simulate potential outcomes of four management
      strategies in adults hospitalized for severe respiratory infection suspected of
      influenza: "immunofluorescence-assay" (IFA) or "polymerase-chain-reaction" (PCR)
      guided oseltamivir treatment, "empirical treatment plus PCR" and "empirical
      treatment alone". Model inputs were derived from literature. The average
      prevalence (11%) of influenza in 2010-2011 (58% being 2009 H1N1) among cases of
      respiratory infections was used in the base-case analysis. Primary outcome
      simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the
      Hong Kong healthcare providers' perspective. RESULTS: In base-case analysis,
      "empirical treatment alone" was shown to be the most cost-effective strategy and
      dominated the other three options. Sensitivity analyses showed that "PCR-guided
      treatment" would dominate "empirical treatment alone" when the daily cost of
      oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the
      predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the
      threshold of willingness-to-pay, "empirical treatment alone" and "PCR-guided
      treatment" were cost-effective 97% and 3% of time, respectively, in 10,000 Monte
      Carlo simulations. CONCLUSIONS: During influenza epidemics, empirical antiviral
      treatment appears to be a cost-effective strategy in managing patients
      hospitalized with severe respiratory infection suspected of influenza, from the
      perspective of healthcare providers in Hong Kong.

PMID- 22479364
TI  - Knock-down of core proteins regulating microRNA biogenesis has no effect on
      sensitivity of lung cancer cells to ionizing radiation.
AB  - Recent studies underline the important role of microRNAs (miRNA) in the
      development of lung cancer. The main regulators of miRNA biogenesis are the
      ribonucleases Drosha, Dicer and Ago2. Here the role of core proteins of miRNA
      biogenesis machinery in the response of human non-small and small cell lung
      carcinoma cell lines to treatment with ionizing radiation was assessed. We found
      that Drosha and Dicer were expressed at higher levels in radioresistant but not
      in sensitive cell lines. However, down-regulation of either Dicer or Drosha had
      no effect on the sensitivity of cells to irradiation. Elimination of components
      of the RNA-induced silencing complex Ago2 and Tudor staphylococcal nuclease also
      did not sensitize cells to the same treatment. Thus, modulation of miRNA
      biogenesis machinery is not sufficient to increase the radiosensitivity of lung
      tumors and other strategies are required to combat lung cancer.

PMID- 22479365
TI  - Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice.
AB  - BACKGROUND: Decrease in lacrimal gland secretory function is related to age
      induced dry eye disease. Lactoferrin, the main glycoprotein component of tears,
      has multiple functions, including anti-inflammatory effects and the promotion of
      cell growth. We investigated how oral administration of lactoferrin affects age
      related lacrimal dysfunction. METHODS AND FINDINGS: Twelve-month-old male
      C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral
      lactoferrin treatment group. Tear function was measured at a 6-month time-point.
      After euthanasia, the lacrimal glands were subjected to histological examination
      with 8-hydroxy-2'-deoxyguanosine (8-OHdG) antibodies, and serum concentrations of
      8-OHdG and hexanoyl-lysine adduct (HEL) were evaluated. Additionally, monocyte
      chemotactic protein-1(MCP-1) and tumor necrosis factor-alpha (TNF-alpha) gene
      expression levels were determined by real-time PCR. The volume of tear secretion
      was significantly larger in the treated group than in the control. Lactoferrin
      administration reduced inflammatory cell infiltration and the MCP-1 and TNF-alpha
      expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin
      group were lower than those in the control group and were associated with
      attenuated 8-OHdG immunostaining of the lacrimal glands. CONCLUSION: Oral
      lactoferrin administration preserves lacrimal gland function in aged mice by
      attenuating oxidative damage and suppressing subsequent gland inflammation.

PMID- 22479366
TI  - Granzyme B cleaves decorin, biglycan and soluble betaglycan, releasing active
      transforming growth factor-beta1.
AB  - OBJECTIVE: Granzyme B (GrB) is a pro-apoptotic serine protease that contributes
      to immune-mediated target cell apoptosis. However, during inflammation, GrB
      accumulates in the extracellular space, retains its activity, and is capable of
      cleaving extracellular matrix (ECM) proteins. Recent studies have implicated a
      pathogenic extracellular role for GrB in cardiovascular disease, yet the
      pathophysiological consequences of extracellular GrB activity remain largely
      unknown. The objective of this study was to identify proteoglycan (PG) substrates
      of GrB and examine the ability of GrB to release PG-sequestered TGF-beta1 into
      the extracellular milieu. METHODS/RESULTS: Three extracellular GrB PG substrates
      were identified; decorin, biglycan and betaglycan. As all of these PGs sequester
      active TGF-beta1, cytokine release assays were conducted to establish if GrB
      mediated PG cleavage induced TGF-beta1 release. Our data confirmed that GrB
      liberated TGF-beta1 from all three substrates as well as from endogenous ECM and
      this process was inhibited by the GrB inhibitor 3,4-dichloroisocoumarin. The
      released TGF-beta1 retained its activity as indicated by the induction of SMAD-3
      phosphorylation in human coronary artery smooth muscle cells. CONCLUSION: In
      addition to contributing to ECM degradation and the loss of tissue structural
      integrity in vivo, increased extracellular GrB activity is also capable of
      inducing the release of active TGF-beta1 from PGs.

PMID- 22479367
TI  - Protein quality control disruption by PKCbetaII in heart failure; rescue by the
      selective PKCbetaII inhibitor, betaIIV5-3.
AB  - Myocardial remodeling and heart failure (HF) are common sequelae of many forms of
      cardiovascular disease and a leading cause of mortality worldwide. Accumulation
      of damaged cardiac proteins in heart failure has been described. However, how
      protein quality control (PQC) is regulated and its contribution to HF development
      are not known. Here, we describe a novel role for activated protein kinase C
      isoform betaII (PKCbetaII) in disrupting PQC. We show that active PKCbetaII
      directly phosphorylated the proteasome and inhibited proteasomal activity in
      vitro and in cultured neonatal cardiomyocytes. Importantly, inhibition of
      PKCbetaII, using a selective PKCbetaII peptide inhibitor (betaIIV5-3), improved
      proteasomal activity and conferred protection in cultured neonatal
      cardiomyocytes. We also show that sustained inhibition of PKCbetaII increased
      proteasomal activity, decreased accumulation of damaged and misfolded proteins
      and increased animal survival in two rat models of HF. Interestingly, betaIIV5-3
      mediated protection was blunted by sustained proteasomal inhibition in HF.
      Finally, increased cardiac PKCbetaII activity and accumulation of misfolded
      proteins associated with decreased proteasomal function were found also in
      remodeled and failing human hearts, indicating a potential clinical relevance of
      our findings. Together, our data highlights PKCbetaII as a novel inhibitor of
      proteasomal function. PQC disruption by increased PKCbetaII activity in vivo
      appears to contribute to the pathophysiology of heart failure, suggesting that
      PKCbetaII inhibition may benefit patients with heart failure. (218 words).

PMID- 22479368
TI  - Financial incentive increases CPAP acceptance in patients from low socioeconomic
      background.
AB  - OBJECTIVE: We explored whether financial incentives have a role in patients'
      decisions to accept (purchase) a continuous positive airway pressure (CPAP)
      device in a healthcare system that requires cost sharing. DESIGN: Longitudinal
      interventional study. PATIENTS: The group receiving financial incentive (n = 137,
      50.8+/-10.6 years, apnea/hypopnea index (AHI) 38.7+/-19.9 events/hr) and the
      control group (n = 121, 50.9+/-10.3 years, AHI 39.9+/-22) underwent attendant
      titration and a two-week adaptation to CPAP. Patients in the control group had a
      co-payment of $330-660; the financial incentive group paid a subsidized price of
      $55. RESULTS: CPAP acceptance was 43% greater (p = 0.02) in the financial
      incentive group. CPAP acceptance among the low socioeconomic strata (n = 113)
      (adjusting for age, gender, BMI, tobacco smoking) was enhanced by financial
      incentive (OR, 95% CI) (3.43, 1.09-10.85), age (1.1, 1.03-1.17), AHI (>30 vs.
      <30) (4.87, 1.56-15.2), and by family/friends who had positive experience with
      CPAP (4.29, 1.05-17.51). Among average/high-income patients (n = 145) CPAP
      acceptance was affected by AHI (>30 vs. <30) (3.16, 1.14-8.75), living with a
      partner (8.82, 1.03-75.8) but not by the financial incentive. At one-year follow
      up CPAP adherence was similar in the financial incentive and control groups, 35%
      and 39%, respectively (p = 0.82). Adherence rate was sensitive to education (+yr)
      (1.28, 1.06-1.55) and AHI (>30 vs. <30) (5.25, 1.34-18.5). CONCLUSIONS:
      Minimizing cost sharing reduces a barrier for CPAP acceptance among low
      socioeconomic status patients. Thus, financial incentive should be applied as a
      policy to encourage CPAP treatment, especially among low socioeconomic strata
      patients.

PMID- 22479369
TI  - Effect of polymorphisms in XPD on clinical outcomes of platinum-based
      chemotherapy for Chinese non-small cell lung cancer patients.
AB  - PURPOSE: Xeroderma pigmentosum group D (XPD) codes for a DNA helicase involved in
      nucleotide excision repair that removes platinum-induced DNA damage. Genetic
      polymorphisms of XPD may affect DNA repair capacity and lead to individual
      differences in the outcome of patients after chemotherapy. This study aims to
      identify whether XPD polymorphisms affect clinical efficacy among advanced non
      small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.
      EXPERIMENTAL DESIGN: 353 stage III-IV NSCLC patients receiving platinum-based
      chemotherapy as the first-line treatment were enrolled in this study. Four
      potentially functional XPD polymorphisms (Arg(156)Arg, Asp(312)Asn, Asp(711)Asp
      and Lys(751)Gln) were genotyped by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry or PCR-based sequencing. RESULTS: Variant
      genotypes of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln were significantly
      associated with poorer NSCLC survival (P = 0.006, 0.006, 0.014, respectively, by
      log-rank test). The most common haplotype GCA (in order of Asp(312)Asn,
      Asp(711)Asp and Lys(751)Gln) also exhibited significant risk effect on NSCLC
      survival (log-rank P = 0.001). This effect was more predominant for patients with
      stage IIIB disease (P = 2.21*10(-4), log-rank test). Increased risks for variant
      haplotypes of XPD were also observed among patients with performance status of 0
      1 and patients with adenocarcinoma. However, no significant associations were
      found between these polymorphisms, chemotherapy response and PFS. CONCLUSIONS:
      Our study provides evidence for the predictive role of XPD Asp(312)Asn,
      Asp(711)Asp and Lys(751)Gln polymorphisms/haplotype on NSCLC prognosis in
      inoperable advanced NSCLC patients treated with platinum-based chemotherapy.

PMID- 22479370
TI  - Phrase frequency effects in language production.
AB  - A classic debate in the psychology of language concerns the question of the grain
      size of the linguistic information that is stored in memory. One view is that
      only morphologically simple forms are stored (e.g., 'car', 'red'), and that more
      complex forms of language such as multi-word phrases (e.g., 'red car') are
      generated on-line from the simple forms. In two experiments we tested this view.
      In Experiment 1, participants produced noun+adjective and noun+noun phrases that
      were elicited by experimental displays consisting of colored line drawings and
      two superimposed line drawings. In Experiment 2, participants produced
      noun+adjective and determiner+noun+adjective utterances elicited by colored line
      drawings. In both experiments, naming latencies decreased with increasing
      frequency of the multi-word phrase, and were unaffected by the frequency of the
      object name in the utterance. These results suggest that the language system is
      sensitive to the distribution of linguistic information at grain-sizes beyond
      individual words.

PMID- 22479371
TI  - Chromium stress mitigation by polyamine-brassinosteroid application involves
      phytohormonal and physiological strategies in Raphanus sativus L.
AB  - Brassinosteroids (BRs) and polyamines (PAs) are well-established growth
      regulators playing key roles in stress management among plants. In the present
      study, we evaluated the effects of epibrassinolide (EBL, an active BR) and
      spermidine (Spd, an active PA) on the tolerance of radish to oxidative stress
      induced by Cr (VI) metal. Our investigation aimed to study the impacts of EBL
      (10(-9) M) and/or Spd (1 mM) on the biochemical and physiological responses of
      radish (Raphanus sativus L.) under Cr-stress. Applications of EBL and/or Spd were
      found to improve growth of Cr-stressed seedlings in terms of root length, shoot
      length and fresh weight. Our data also indicated that applications of EBL and Spd
      have significant impacts, particularly when applied together, on the endogenous
      titers of PAs, free and bound forms of IAA and ABA in seedlings treated with Cr
      stress. Additionally, co-applications of EBL and Spd modulated more remarkably
      the titers of antioxidants (glutathione, ascorbic acid, proline, glycine betaine
      and total phenol) and activities of antioxidant enzymes (guaicol peroxidase,
      catalase, superoxide dismutase and glutathione reductase) in Cr-stressed plants
      than their individual applications. Attenuation of Cr-stress by EBL and/or Spd
      (more efficient with EBL and Spd combination) was also supported by enhanced
      values of stress indices, such as phytochelatins, photosynthetic pigments and
      total soluble sugars, and reduction in malondialdehyde and H(2)O(2) levels in Cr
      treated seedlings. Diminution of ROS production and enhanced ROS scavenging
      capacities were also noted for EBL and/or Spd under Cr-stress. However, no
      significant reduction in Cr uptake was observed for co-application of EBL and Spd
      when compared to their individual treatments in Cr-stressed seedlings. Taken
      together, our results demonstrate that co-applications of EBL and Spd are more
      effective than their independent treatments in lowering the Cr-induced oxidative
      stress in radish, leading to improved growth of radish seedlings under Cr-stress.

PMID- 22479372
TI  - Genome wide analysis of acute myeloid leukemia reveal leukemia specific methylome
      and subtype specific hypomethylation of repeats.
AB  - Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP
      seq) has the potential to identify changes in DNA methylation important in cancer
      development. In order to understand the role of epigenetic modulation in the
      development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA
      of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia
      associated differentially methylated regions that included gene promoters, gene
      bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with
      significantly methylated promoters were of interest and further analysis of their
      expression showed them to be repressed in AML. We also demonstrated considerable
      cytogenetic subtype specificity in the methylomes affecting different genomic
      features. Significantly distinct patterns of hypomethylation of certain
      interspersed repeat elements were associated with cytogenetic subtypes. The
      methylation patterns of members of the SINE family tightly clustered all leukemic
      patients with an enrichment of Alu repeats with a high CpG density (P<0.0001). We
      were able to demonstrate significant inverse correlation between intragenic
      interspersed repeat sequence methylation and gene expression with SINEs showing
      the strongest inverse correlation (R(2) = 0.7). We conclude that the alterations
      in DNA methylation that accompany the development of AML affect not only the
      promoters, but also the non-promoter genomic features, with significant
      demethylation of certain interspersed repeat DNA elements being associated with
      AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite
      pyrosequencing and the Infinium array.

PMID- 22479373
TI  - Light and heavy fractions of soil organic matter in response to climate warming
      and increased precipitation in a temperate steppe.
AB  - Soil is one of the most important carbon (C) and nitrogen (N) pools and plays a
      crucial role in ecosystem C and N cycling. Climate change profoundly affects soil
      C and N storage via changing C and N inputs and outputs. However, the influences
      of climate warming and changing precipitation regime on labile and recalcitrant
      fractions of soil organic C and N remain unclear. Here, we investigated soil
      labile and recalcitrant C and N under 6 years' treatments of experimental warming
      and increased precipitation in a temperate steppe in Northern China. We measured
      soil light fraction C (LFC) and N (LFN), microbial biomass C (MBC) and N (MBN),
      dissolved organic C (DOC) and heavy fraction C (HFC) and N (HFN). The results
      showed that increased precipitation significantly stimulated soil LFC and LFN by
      16.1% and 18.5%, respectively, and increased LFC:HFC ratio and LFN:HFN ratio,
      suggesting that increased precipitation transferred more soil organic carbon into
      the quick-decayed carbon pool. Experimental warming reduced soil labile C (LFC,
      MBC, and DOC). In contrast, soil heavy fraction C and N, and total C and N were
      not significantly impacted by increased precipitation or warming. Soil labile C
      significantly correlated with gross ecosystem productivity, ecosystem respiration
      and soil respiration, but not with soil moisture and temperature, suggesting that
      biotic processes rather than abiotic factors determine variations in soil labile
      C. Our results indicate that certain soil carbon fraction is sensitive to climate
      change in the temperate steppe, which may in turn impact ecosystem carbon fluxes
      in response and feedback to climate change.

PMID- 22479374
TI  - A novel rapid DNA microarray assay enables identification of 37 Mycoplasma
      species and highlights multiple Mycoplasma infections.
AB  - Mycoplasmas comprise a conglomerate of pathogens and commensals occurring in
      humans and animals. The genus Mycoplasma alone contains more than 120 species at
      present, and new members are continuously being discovered. Therefore, it seems
      promising to use a single highly parallel detection assay rather than develop
      separate tests for each individual species. In this study, we have designed a DNA
      microarray carrying 70 oligonucleotide probes derived from the 23S rRNA gene and
      86 probes from the tuf gene target regions. Following a PCR amplification and
      biotinylation step, hybridization on the array was shown to specifically identify
      31 Mycoplasma spp., as well as 3 Acholeplasma spp. and 3 Ureaplasma spp. Members
      of the Mycoplasma mycoides cluster can be recognized at subgroup level. This
      procedure enables parallel detection of Mollicutes spp. occurring in humans,
      animals or cell culture, from mono- and multiple infections, in a single run. The
      main advantages of the microarray assay include ease of operation, rapidity, high
      information content, and affordability. The new test's analytical sensitivity is
      equivalent to that of real-time PCR and allows examination of field samples
      without the need for culture. When 60 field samples from ruminants and birds
      previously analyzed by denaturing-gradient gel electrophoresis (DGGE) were tested
      by the microarray assay both tests identified the same agent in 98.3% of the
      cases. Notably, microarray testing revealed an unexpectedly high proportion (35%)
      of multiple mycoplasma infections, i.e., substantially more than DGGE (15%). Two
      of the samples were found to contain four different Mycoplasma spp. This
      phenomenon deserves more attention, particularly its implications for
      epidemiology and treatment.

PMID- 22479375
TI  - Efficacy of an educational material on second primary cancer screening practice
      for cancer survivors: a randomized controlled trial.
AB  - BACKGROUND: Cancer surivors have limited knowledge about second primary cancer
      (SPC) screening and suboptimal rates of completion of screening practices for
      SPC. Our objective was to test the efficacy of an educational material on the
      knowledge, attitudes, and screening practices for SPC among cancer survivors.
      METHODS: Randomized, controlled trial among 326 cancer survivors from 6 oncology
      care outpatient clinics in Korea. Patients were randomized to an intervention or
      an attention control group. The intervention was a photo-novel, culturally
      tailored to increase knowledge about SPC screening. Knowledge and attitudes
      regarding SPC screening were assessed two weeks after the intervention, and
      screening practices were assessed after one year. RESULTS: At two weeks post
      intervention, the average knowledge score was significantly higher in the
      intervention compared to the control group (0.81 vs. 0.75, P<0.01), with no
      significant difference in their attitude scores (2.64 vs. 2.57, P = 0.18). After
      1 year of follow-up, the completion rate of all appropriate cancer screening was
      47.2% in both intervention and control groups. CONCLUSION: While the educational
      material was effective for increasing knowledge of SPC screening, it did not
      promote cancer screening practice among cancer survivors. More effective
      interventions are needed to increase SPC screening rates in this population.
      TRIAL REGISTRATION: ClinicalTrial.gov NCT00948337.

PMID- 22479376
TI  - Identifying overlapping and hierarchical thematic structures in networks of
      scholarly papers: a comparison of three approaches.
AB  - The aim of this paper is to introduce and assess three algorithms for the
      identification of overlapping thematic structures in networks of papers. We
      implemented three recently proposed approaches to the identification of
      overlapping and hierarchical substructures in graphs and applied the
      corresponding algorithms to a network of 492 information-science papers coupled
      via their cited sources. The thematic substructures obtained and overlaps
      produced by the three hierarchical cluster algorithms were compared to a content
      based categorisation, which we based on the interpretation of titles, abstracts,
      and keywords. We defined sets of papers dealing with three topics located on
      different levels of aggregation: h-index, webometrics, and bibliometrics. We
      identified these topics with branches in the dendrograms produced by the three
      cluster algorithms and compared the overlapping topics they detected with one
      another and with the three predefined paper sets. We discuss the advantages and
      drawbacks of applying the three approaches to paper networks in research fields.

PMID- 22479377
TI  - Identification and functional analysis of a novel von Willebrand factor mutation
      in a family with type 2A von Willebrand disease.
AB  - von Willebrand factor (VWF) is essential for normal hemostasis. VWF gene
      mutations cause the hemorrhagic von Willebrand disease (VWD). In this study, a 9
      year-old boy was diagnosed as type 2A VWD, based on a history of abnormal
      bleeding, low plasma VWF antigen and activity, low plasma factor VIII activity,
      and lack of plasma high-molecular-weight (HMW) VWF multimers. Sequencing analysis
      detected a 6-bp deletion in exon 28 of his VWF gene, which created a mutant
      lacking D1529V1530 residues in VWF A2 domain. This mutation also existed in his
      family members with abnormal bleedings but not in >60 normal controls. In
      transfected HEK293 cells, recombinant VWF DeltaD1529V1530 protein had markedly
      reduced levels in the conditioned medium (42+/-4% of wild-type (WT) VWF, p<0.01).
      The mutant VWF in the medium had less HMW multimers. In contrast, the
      intracellular levels of the mutant VWF in the transfected cells were
      significantly higher than that of WT (174+/-29%, p<0.05), indicating
      intracellular retention of the mutant VWF. In co-transfection experiments, the
      mutant reduced WT VWF secretion from the cells. By immunofluorescence staining,
      the retention of the mutant VWF was identified within the endoplasmic reticulum
      (ER). Together, we identified a unique VWF mutation responsible for the bleeding
      phenotype in a patient family with type 2A VWD. The mutation impaired VWF
      trafficking through the ER, thereby preventing VWF secretion from the cells. Our
      results illustrate the diversity of VWF gene mutations, which contributes to the
      wide spectrum of VWD.

PMID- 22479378
TI  - Evaluation of genetic mutations associated with Mycobacterium tuberculosis
      resistance to amikacin, kanamycin and capreomycin: a systematic review.
AB  - BACKGROUND: Rapid molecular diagnostics for detecting multidrug-resistant and
      extensively drug-resistant tuberculosis (M/XDR-TB) primarily identify mutations
      in Mycobacterium tuberculosis (Mtb) genes associated with drug resistance. Their
      accuracy, however, is dependent largely on the strength of the association
      between a specific mutation and the phenotypic resistance of the isolate with
      that mutation, which is not always 100%. While this relationship is well
      established and reliable for first-line anti-TB drugs, rifampin and isoniazid, it
      is less well-studied and understood for second-line, injectable drugs, amikacin
      (AMK), kanamycin (KAN) and capreomycin (CAP). METHODOLOGY/PRINCIPAL FINDINGS: We
      conducted a systematic review of all published studies evaluating Mtb mutations
      associated with resistance to AMK, KAN, CAP in order to characterize the
      diversity and frequency of mutations as well as describe the strength of the
      association between specific mutations and phenotypic resistance in global
      populations. Our objective was to determine the potential utility and reliability
      of these mutations as diagnostic markers for detecting AMK, KAN and CAP
      resistance. Mutation data was reviewed for 1,585 unique clinical isolates from
      four continents and over 18 countries. Mutations in the rrs, tlyA, eis promoter
      and gidB genes were associated with AMK, KAN and/or CAP resistance.
      CONCLUSIONS/SIGNIFICANCE: The rrs A1401G mutation was present in the majority of
      AMK, KAN and CAP resistant Mtb strains reviewed, but was also found in 7% of CAP
      susceptible strains. The 1401 mutation alone, however, was not found with
      sufficient frequency to detect more than 70-80% of global Mtb strains resistant
      to AMK and CAP, and 60% of strains resistant to KAN. Additional mutations in the
      rrs, eis promoter, tlyA and gidB genes appear to be associated with resistance
      and could improve sensitivity and specificity of future diagnostics.

PMID- 22479379
TI  - Selection of reference genes for quantitative gene expression studies in
      Platycladus orientalis (Cupressaceae) Using real-time PCR.
AB  - Platycladus orientalis is a tree species that is highly resistant, widely
      adaptable, and long-lived, with lifespans of even thousands of years. To explore
      the mechanisms underlying these characteristics, gene expressions have been
      investigated at the transcriptome level by RNA-seq combined with a digital gene
      expression (DGE) technique. So, it is crucial to have a reliable set of reference
      genes to normalize the expressions of genes in P. orientalis under various
      conditions using the most accurate and sensitive method of quantitative real-time
      PCR (qRT-PCR). In this study, we selected 10 reference gene candidates from
      transcriptome data of P. orientalis, and examined their expression profiles by
      qRT-PCR using 29 different samples of P. orientalis, which were collected from
      plants of different ages, different tissues, and plants subjected to different
      treatments including cold, heat, salinity, polyethylene glycol (PEG), and
      abscisic acid (ABA). Three analytical software packages (geNorm, Bestkeeper, and
      NormFinder) were used to assess the stability of gene expression. The results
      showed that ubiquitin-conjugating enzyme E2 (UBC) and alpha-tubulin (aTUB) were
      the optimum pair of reference genes at all developmental stages and under all
      stress conditions. ACT7 was the most stable gene across different tissues and
      cold-treated samples, while UBQ was the most stably expressed reference gene for
      NaCl- and ABA-treated samples. In parallel, aTUB and UBC were used singly or in
      combination as reference genes to examine the expression levels of NAC (a homolog
      of AtNAC2) in plants subjected to various treatments with qRT-PCR. The results
      further proved the reliability of the two selected reference genes. Our study
      will benefit future research on the expression of genes in response to
      stress/senescence in P. orientalis and other members of the Cupressaceae.

PMID- 22479380
TI  - Genetic and non-genetic influences during pregnancy on infant global and site
      specific DNA methylation: role for folate gene variants and vitamin B12.
AB  - Inter-individual variation in patterns of DNA methylation at birth can be
      explained by the influence of environmental, genetic and stochastic factors. This
      study investigates the genetic and non-genetic determinants of variation in DNA
      methylation in human infants. Given its central role in provision of methyl
      groups for DNA methylation, this study focuses on aspects of folate metabolism.
      Global (LUMA) and gene specific (IGF2, ZNT5, IGFBP3) DNA methylation were
      quantified in 430 infants by Pyrosequencing(r). Seven polymorphisms in 6 genes
      (MTHFR, MTRR, FOLH1, CbetaS, RFC1, SHMT) involved in folate absorption and
      metabolism were analysed in DNA from both infants and mothers. Red blood cell
      folate and serum vitamin B(12) concentrations were measured as indices of vitamin
      status. Relationships between DNA methylation patterns and several covariates
      viz. sex, gestation length, maternal and infant red cell folate, maternal and
      infant serum vitamin B(12), maternal age, smoking and genotype were tested.
      Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p =
      0.032) and inversely with ZNT5 methylation (rho = -0.13, p = 0.017). Methylation
      of the IGFBP3 locus correlated inversely with infant vitamin B(12) concentration
      (rho = -0.16, p = 0.007), whilst global DNA methylation correlated inversely with
      maternal vitamin B(12) concentrations (rho = 0.18, p = 0.044). Analysis of common
      genetic variants in folate pathway genes highlighted several associations
      including infant MTRR 66G>A genotype with DNA methylation (chi(2) = 8.82, p =
      0.003) and maternal MTHFR 677C>T genotype with IGF2 methylation (chi(2) = 2.77, p
      = 0.006). These data support the hypothesis that both environmental and genetic
      factors involved in one-carbon metabolism influence DNA methylation in infants.
      Specifically, the findings highlight the importance of vitamin B(12) status,
      infant MTRR genotype and maternal MTHFR genotype, all of which may influence the
      supply of methyl groups for DNA methylation. In addition, gestational length
      appears to be an important determinant of infant DNA methylation patterns.

PMID- 22479381
TI  - A sensitive branched DNA HIV-1 signal amplification viral load assay with single
      day turnaround.
AB  - Branched DNA (bDNA) is a signal amplification technology used in clinical and
      research laboratories to quantitatively detect nucleic acids. An overnight
      incubation is a significant drawback of highly sensitive bDNA assays. The
      VERSANT(r) HIV-1 RNA 3.0 Assay (bDNA) ("Versant Assay") currently used in
      clinical laboratories was modified to allow shorter target incubation, enabling
      the viral load assay to be run in a single day. To dramatically reduce the target
      incubation from 16-18 h to 2.5 h, composition of only the "Lysis Diluent"
      solution was modified. Nucleic acid probes in the assay were unchanged.
      Performance of the modified assay (assay in development; not commercially
      available) was evaluated and compared to the Versant Assay. Dilution series
      replicates (>950 results) were used to demonstrate that analytical sensitivity,
      linearity, accuracy, and precision for the shorter modified assay are comparable
      to the Versant Assay. HIV RNA-positive clinical specimens (n = 135) showed no
      significant difference in quantification between the modified assay and the
      Versant Assay. Equivalent relative quantification of samples of eight genotypes
      was demonstrated for the two assays. Elevated levels of several potentially
      interfering endogenous substances had no effect on quantification or specificity
      of the modified assay. The modified assay with drastically improved turnaround
      time demonstrates the viability of signal-amplifying technology, such as bDNA, as
      an alternative to the PCR-based assays dominating viral load monitoring in
      clinical laboratories. Highly sensitive bDNA assays with a single day turnaround
      may be ideal for laboratories with especially stringent cost, contamination, or
      reliability requirements.

PMID- 22479382
TI  - RUNX3 regulates intercellular adhesion molecule 3 (ICAM-3) expression during
      macrophage differentiation and monocyte extravasation.
AB  - The adhesion molecule ICAM-3 belongs to the immunoglobulin gene superfamily and
      functions as a ligand for the beta2 integrins LFA-1, Mac-1 and alpha(d)beta(2).
      The expression of ICAM-3 is restricted to cells of the hematopoietic lineage. We
      present evidences that the ICAM-3 gene promoter exhibits a leukocyte-specific
      activity, as its activity is significantly higher in ICAM-3+ hematopoietic cell
      lines. The activity of the ICAM-3 gene promoter is dependent on the occupancy of
      RUNX cognate sequences both in vitro and in vivo, and whose integrity is required
      for RUNX responsiveness and for the cooperative actions of RUNX with
      transcription factors of the Ets and C/EBP families. Protein analysis revealed
      that ICAM-3 levels diminish upon monocyte-derived macrophage differentiation,
      monocyte transendothelial migration and dendritic cell maturation, changes that
      correlate with an increase in RUNX3. Importantly, disruption of RUNX-binding
      sites led to enhanced promoter activity, and small interfering RNA-mediated
      reduction of RUNX3 expression resulted in increased ICAM-3 mRNA levels.
      Altogether these results indicate that the ICAM-3 gene promoter is negatively
      regulated by RUNX transcription factors, which contribute to the leukocyte
      restricted and the regulated expression of ICAM-3 during monocyte-to-macrophage
      differentiation and monocyte extravasation.

PMID- 22479383
TI  - Centromere plasmid: a new genetic tool for the study of Plasmodium falciparum.
AB  - The introduction of transgenes into Plasmodium falciparum, a highly virulent
      human malaria parasite, has been conducted either by single crossover
      recombination or by using episomal plasmids. However, these techniques remain
      insufficient because of the low transfection efficiency and the low frequency of
      recombination. To improve the genetic manipulation of P. falciparum, we developed
      the centromere plasmid as a new genetic tool. First, we attempted to clone all of
      the predicted centromeres from P. falciparum into E. coli cells but failed
      because of the high A/T contents of these sequences. To overcome this difficulty,
      we identified the common sequence features of the centromere of Plasmodium spp.
      and designed a small centromere that retained those features. The centromere
      plasmid constructed with the small centromere sequence, pFCEN, segregated into
      daughter parasites with approximately 99% efficiency, resulting in the stable
      maintenance of this plasmid in P. falciparum even in the absence of drug
      selection. This result demonstrated that the small centromere sequence harboured
      in pFCEN could function as an actual centromere in P. falciparum. In addition,
      transgenic parasites were more rapidly generated when using pFCEN than when using
      the control plasmid, which did not contain the centromere sequence. Furthermore,
      in contrast to the control plasmid, pFCEN did not form concatemers and, thus, was
      maintained as a single copy over multiple cell divisions. These unique properties
      of the pFCEN plasmid will solve the current technical limitations of the genetic
      manipulation of P. falciparum, and thus, this plasmid will become a standard
      genetic tool for the study of this parasite.

PMID- 22479384
TI  - Detection of recent HIV-1 infection using a new limiting-antigen avidity assay:
      potential for HIV-1 incidence estimates and avidity maturation studies.
AB  - BACKGROUND: Accurate and reliable laboratory methods are needed for estimation of
      HIV-1 incidence to identify the high-risk populations and target and monitor
      prevention efforts. We previously described a single-well limiting-antigen
      avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection.
      METHODS: We describe here further optimization and characterization of LAg
      Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA.
      Specimen sets included longitudinal sera (n = 393), collected from 89
      seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera
      from AIDS patients (n = 488) with or without TB co-infections from 3 different
      cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The
      BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed.
      RESULTS: Monitoring quality control specimens indicated high reproducibility of
      the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range.
      The LAg-Avidity EIA has an overall mean duration of recency (omega) of 141 days
      (95% CI 119-160) at normalized optical density (ODn) cutoff of 1.0, with similar
      omega in different HIV-1 subtypes and populations (132 to 143 days). Antibody
      avidity kinetics were similar among individuals and subtypes by both the LAg
      Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay.
      The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity
      EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with
      increasing avidity confirm accurate detection of recent HIV-1 infections.
      CONCLUSIONS: These data demonstrate that the LAg-Avidity EIA is a promising assay
      with consistent omega in different populations and subtypes. The assay should be
      very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as
      part of HIV surveillance, 2) identifying risk factors for recent infections, 3)
      measuring impact of prevention programs, and 4) studying avidity maturation
      during vaccine trials.

PMID- 22479385
TI  - Abnormal pulmonary artery stiffness in pulmonary arterial hypertension: in vivo
      study with intravascular ultrasound.
AB  - BACKGROUND: There is increasing recognition that pulmonary artery stiffness is an
      important determinant of right ventricular (RV) afterload in pulmonary arterial
      hypertension (PAH). We used intravascular ultrasound (IVUS) to evaluate the
      mechanical properties of the elastic pulmonary arteries (PA) in subjects with
      PAH, and assessed the effects of PAH-specific therapy on indices of arterial
      stiffness. METHOD: Using IVUS and simultaneous right heart catheterisation, 20
      pulmonary segments in 8 PAH subjects and 12 pulmonary segments in 8 controls were
      studied to determine their compliance, distensibility, elastic modulus and
      stiffness index beta. PAH subjects underwent repeat IVUS examinations after 6
      months of bosentan therapy. RESULTS: AT BASELINE, PAH SUBJECTS DEMONSTRATED
      GREATER STIFFNESS IN ALL MEASURED INDICES COMPARED TO CONTROLS: compliance
      (1.50+/-0.11*10(-2) mm(2/)mmHg vs 4.49+/-0.43*10(-2) mm(2/)mmHg, p<0.0001),
      distensibility (0.32+/-0.03%/mmHg vs 1.18+/-0.13%/mmHg, p<0.0001), elastic
      modulus (720+/-64 mmHg vs 198+/-19 mmHg, p<0.0001), and stiffness index beta
      (15.0+/-1.4 vs 11.0+/-0.7, p = 0.046). Strong inverse exponential associations
      existed between mean pulmonary artery pressure and compliance (r(2) = 0.82,
      p<0.0001), and also between mean PAP and distensibility (r(2) = 0.79, p = 0.002).
      Bosentan therapy, for 6-months, was not associated with any significant changes
      in all indices of PA stiffness. CONCLUSION: Increased stiffness occurs in the
      proximal elastic PA in patients with PAH and contributes to the pathogenesis RV
      failure. Bosentan therapy may not be effective at improving PA stiffness.

PMID- 22479386
TI  - Extensions of MADM (mosaic analysis with double markers) in mice.
AB  - Mosaic Analysis with Double Markers (MADM) is a method for generating genetically
      mosaic mice, in which sibling mutant and wild-type cells are labeled with
      different fluorescent markers. It is a powerful tool that enables analysis of
      gene function at the single cell level in vivo. It requires transgenic cassettes
      to be located between the centromere and the mutation in the gene of interest on
      the same chromosome. Here we compare procedures for introduction of MADM
      cassettes into new loci in the mouse genome, and describe new approaches for
      expanding the utility of MADM. We show that: 1) Targeted homologous recombination
      outperforms random transgenesis in generation of reliably expressed MADM
      cassettes, 2) MADM cassettes in new genomic loci need to be validated for
      biallelic and ubiquitous expression, 3) Recombination between MADM cassettes on
      different chromosomes can be used to study reciprocal chromosomal
      deletions/duplications, and 4) MADM can be modified to permit transgene
      expression by combining it with a binary expression system. The advances
      described in this study expand current, and enable new and more versatile
      applications of MADM.

PMID- 22479387
TI  - Persistent cell-autonomous circadian oscillations in fibroblasts revealed by six
      week single-cell imaging of PER2::LUC bioluminescence.
AB  - Biological oscillators naturally exhibit stochastic fluctuations in period and
      amplitude due to the random nature of molecular reactions. Accurately measuring
      the precision of noisy oscillators and the heterogeneity in period and strength
      of rhythmicity across a population of cells requires single-cell recordings of
      sufficient length to fully represent the variability of oscillations. We found
      persistent, independent circadian oscillations of clock gene expression in 6-week
      long bioluminescence recordings of 80 primary fibroblast cells dissociated from
      PER2::LUC mice and kept in vitro for 6 months. Due to the stochastic nature of
      rhythmicity, the proportion of cells appearing rhythmic increases with the length
      of interval examined, with 100% of cells found to be rhythmic when using 3-week
      windows. Mean period and amplitude are remarkably stable throughout the 6-week
      recordings, with precision improving over time. For individual cells, precision
      of period and amplitude are correlated with cell size and rhythm amplitude, but
      not with period, and period exhibits much less cycle-to-cycle variability (CV
      7.3%) than does amplitude (CV 37%). The time series are long enough to
      distinguish stochastic fluctuations within each cell from differences among
      cells, and we conclude that the cells do exhibit significant heterogeneity in
      period and strength of rhythmicity, which we measure using a novel statistical
      metric. Furthermore, stochastic modeling suggests that these single-cell clocks
      operate near a Hopf bifurcation, such that intrinsic noise enhances the
      oscillations by minimizing period variability and sustaining amplitude.

PMID- 22479388
TI  - Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.
AB  - BACKGROUND: The T-box transcription factor Brachyury (T) is essential for
      formation of the posterior mesoderm and the notochord in vertebrate embryos. Work
      in the frog and the zebrafish has identified some direct genomic targets of
      Brachyury, but little is known about Brachyury targets in the mouse.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we use chromatin immunoprecipitation and
      mouse promoter microarrays to identify targets of Brachyury in embryoid bodies
      formed from differentiating mouse ES cells. The targets we identify are enriched
      for sequence-specific DNA binding proteins and include components of signal
      transduction pathways that direct cell fate in the primitive streak and tailbud
      of the early embryo. Expression of some of these targets, such as Axin2, Fgf8 and
      Wnt3a, is down regulated in Brachyury mutant embryos and we demonstrate that they
      are also Brachyury targets in the human. Surprisingly, we do not observe
      enrichment of the canonical T-domain DNA binding sequence 5'-TCACACCT-3' in the
      vicinity of most Brachyury target genes. Rather, we have identified an (AC)(n)
      repeat sequence, which is conserved in the rat but not in human, zebrafish or
      Xenopus. We do not understand the significance of this sequence, but speculate
      that it enhances transcription factor binding in the regulatory regions of
      Brachyury target genes in rodents. CONCLUSIONS/SIGNIFICANCE: Our work identifies
      the genomic targets of a key regulator of mesoderm formation in the early mouse
      embryo, thereby providing insights into the Brachyury-driven genetic regulatory
      network and allowing us to compare the function of Brachyury in different
      species.

PMID- 22479389
TI  - Identification and characterization of microcin S, a new antibacterial peptide
      produced by probiotic Escherichia coli G3/10.
AB  - Escherichia coli G3/10 is a component of the probiotic drug Symbioflor 2. In an
      in vitro assay with human intestinal epithelial cells, E. coli G3/10 is capable
      of suppressing adherence of enteropathogenic E. coli E2348/69. In this study, we
      demonstrate that a completely novel class II microcin, produced by probiotic E.
      coli G3/10, is responsible for this behavior. We named this antibacterial peptide
      microcin S (MccS). Microcin S is coded on a 50.6 kb megaplasmid of E. coli G3/10,
      which we have completely sequenced and annotated. The microcin S operon is about
      4.7 kb in size and is comprised of four genes. Subcloning of the genes and gene
      fragments followed by gene expression experiments enabled us to functionally
      characterize all members of this operon, and to clearly identify the nucleotide
      sequences encoding the microcin itself (mcsS), its transport apparatus and the
      gene mcsI conferring self immunity against microcin S. Overexpression of cloned
      mcsI antagonizes MccS activity, thus protecting indicator strain E. coli E2348/69
      in the in vitro adherence assay. Moreover, growth of E. coli transformed with a
      plasmid containing mcsS under control of an araC PBAD activator-promoter is
      inhibited upon mcsS induction. Our data provide further mechanistic insight into
      the probiotic behavior of E. coli G3/10.

PMID- 22479390
TI  - Nicorandil attenuates monocrotaline-induced vascular endothelial damage and
      pulmonary arterial hypertension.
AB  - BACKGROUND: An antianginal K(ATP) channel opener nicorandil has various
      beneficial effects on cardiovascular systems; however, its effects on pulmonary
      vasculature under pulmonary arterial hypertension (PAH) have not yet been
      elucidated. Therefore, we attempted to determine whether nicorandil can attenuate
      monocrotaline (MCT)-induced PAH in rats. MATERIALS AND METHODS: Sprague-Dawley
      rats injected intraperitoneally with 60 mg/kg MCT were randomized to receive
      either vehicle; nicorandil (5.0 mg.kg(-1).day(-1)) alone; or nicorandil as well
      as either a K(ATP) channel blocker glibenclamide or a nitric oxide synthase (NOS)
      inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), from immediately or 21
      days after MCT injection. Four or five weeks later, right ventricular systolic
      pressure (RVSP) was measured, and lung tissue was harvested. Also, we evaluated
      the nicorandil-induced anti-apoptotic effects and activation status of several
      molecules in cell survival signaling pathway in vitro using human umbilical vein
      endothelial cells (HUVECs). RESULTS: Four weeks after MCT injection, RVSP was
      significantly increased in the vehicle-treated group (51.0+/-4.7 mm Hg), whereas
      it was attenuated by nicorandil treatment (33.2+/-3.9 mm Hg; P<0.01). Nicorandil
      protected pulmonary endothelium from the MCT-induced thromboemboli formation and
      induction of apoptosis, accompanied with both upregulation of endothelial NOS
      (eNOS) expression and downregulation of cleaved caspase-3 expression. Late
      treatment with nicorandil for the established PAH was also effective in
      suppressing the additional progression of PAH. These beneficial effects of
      nicorandil were blocked similarly by glibenclamide and l-NAME. Next, HUVECs were
      incubated in serum-free medium and then exhibited apoptotic morphology, while
      these changes were significantly attenuated by nicorandil administration.
      Nicorandil activated the phosphatidylinositol 3-kinase (PI3K)/Akt and
      extracellular signal-regulated kinase (ERK) pathways in HUVECs, accompanied with
      the upregulation of both eNOS and Bcl-2 expression. CONCLUSIONS: Nicorandil
      attenuated MCT-induced vascular endothelial damage and PAH through production of
      eNOS and anti-apoptotic factors, suggesting that nicorandil might have a
      promising therapeutic potential for PAH.

PMID- 22479391
TI  - Inter-individual variability and conspecific densities: consequences for
      population regulation and range expansion.
AB  - The presence of conspecifics can strongly modulate the quality of a breeding
      site. Both positive and negative effects of conspecifics can act on the same
      individuals, with the final balance between its costs and benefits depending on
      individual characteristics. A particular case of inter-individual variation found
      in many avian species is chromatic variability. Among birds, plumage coloration
      can co-vary with morphology, physiology and behavior as well as with age. These
      relationships suggest that cost-benefit balances of conspecific presence may be
      different for individuals with different colorations. We investigated whether
      inter-individual variability affects population regulation and expansion
      processes by analyzing potential differences in density-dependent productivity
      and settlement patterns in relation to plumage coloration in a population of a
      long-lived avian species recently undergoing a notable increase in numbers and
      distribution range. Our results show strong variation in the effect of density on
      productivity of breeding pairs depending on plumage coloration of their members.
      Productivity of dark birds decreased along the breeding density gradient while
      that of lighter breeders remained unchanged with conspecific density. In a
      similar way, our results showed an uneven occupation of localities by individuals
      with different plumage coloration in relation to local densities, with the
      breeding of lighter harriers more aggregated than that of dark-brown ones. At a
      population scale, darker birds had higher probability of colonization of the most
      isolated, empty sites. Explanations for species range expansion and population
      regulation usually make the inferred assumption that species traits are similar
      among individuals. However, in most species, there could be individual variation
      in niche requirements or dispersal propensities among individuals with different
      traits. Our results contribute to the growing appreciation that the individual
      traits, but not the average trait at the level of species, are important during
      population regulation and expansion processes.

PMID- 22479392
TI  - Monitoring inequalities in the health workforce: the case study of Brazil 1991
      2005.
AB  - INTRODUCTION: Both the quantity and the distribution of health workers in a
      country are fundamental for assuring equitable access to health services. Using
      the case of Brazil, we measure changes in inequalities in the distribution of the
      health workforce and account for the sources of inequalities at sub-national
      level to identify whether policies have been effective in decreasing inequalities
      and increasing the density of health workers in the poorest areas between 1991
      and 2005. METHODS: With data from Datasus 2005 and the 1991 and 2000 Census we
      measure the Gini and the Theil T across the 4,267 Brazilian Minimum Comparable
      Areas (MCA) for 1991, 2000 and 2005 to investigate changes in inequalities in the
      densities of physicians; nurse professionals; nurse associates; and community
      health workers by states, poverty quintiles and urban-rural stratum to account
      for the sources of inequalities. RESULTS: We find that inequalities have
      increased over time and that physicians and nurse professionals are the
      categories of health workers, which are more unequally distributed across MCA.
      The poorest states experience the highest shortage of health workers (below the
      national average) and have the highest inequalities in the distribution of
      physicians plus nurse professionals (above the national average) in the three
      years. Most of the staff in poor areas are unskilled health workers. Most of the
      overall inequalities in the distribution of health workers across MCA are due to
      inequalities within states, poverty quintiles and rural-urban stratum.
      DISCUSSION: This study highlights some critical issues in terms of the
      geographical distribution of health workers, which are accessible to the poor and
      the new methods have given new insights to identify critical geographical areas
      in Brazil. Eliminating the gap in the health workforce would require policies and
      interventions to be conducted at the state level focused in poor and rural areas.

PMID- 22479393
TI  - Crystal structure of Streptococcus pyogenes Csn2 reveals calcium-dependent
      conformational changes in its tertiary and quaternary structure.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR
      associated (Cas) proteins constitute a microbial immune system against invading
      genetic elements, such as plasmids and phages. Csn2 is an Nmeni subtype-specific
      Cas protein, and was suggested to function in the adaptation process, during
      which parts of foreign nucleic acids are integrated into the host microbial
      genome to enable immunity against future invasion. Here, we report a 2.2 A
      crystal structure of Streptococcus pyogenes Csn2. The structure revealed
      previously unseen calcium-dependent conformational changes in its tertiary and
      quaternary structure. This supports the proposed double-stranded DNA-binding
      function of S. pyogenes Csn2.

PMID- 22479394
TI  - The tyrosine kinase c-Src directly mediates growth factor-induced Notch-1 and
      Furin interaction and Notch-1 activation in pancreatic cancer cells.
AB  - The proteolytic activity of Furin responsible for processing full length Notch-1
      (p300) plays a critical role in Notch signaling. The amplitude and duration of
      Notch activity can be regulated at various points in the pathway, but there has
      been no report regarding regulation of the Notch-1-Furin interaction, despite its
      importance. In the present study, we found that the Notch-1-Furin interaction is
      regulated by the non-receptor tyrosine kinase, c-Src. c-Src and Notch-1 are
      physically associated, and this association is responsible for Notch-1 processing
      and activation. We also found that growth factor TGF-alpha, an EGFR ligand, and
      PDGF-BB, a PDGFR ligand, induce the Notch-1-Furin interaction mediated by c-Src.
      Our results support three new and provocative conclusions: (1) The association
      between Notch-1 and Furin is a well-regulated process; (2) Extracellular growth
      factor signals regulate this interaction, which is mediated by c-Src; (3) There
      is cross-talk between the plasma growth factor receptor-c-Src and Notch pathways.
      Co-localization of Notch-1 and c-Src was confirmed in xenograft tumor tissues and
      in the tissues of pancreatic cancer patients. Our findings have implications for
      the mechanism by which the Notch and growth factor receptor-c-Src signaling
      pathways regulate carcinogenesis and cancer cell growth.

PMID- 22479395
TI  - Molecular phylogenetic evaluation of classification and scenarios of character
      evolution in calcareous sponges (Porifera, Class Calcarea).
AB  - Calcareous sponges (Phylum Porifera, Class Calcarea) are known to be
      taxonomically difficult. Previous molecular studies have revealed many
      discrepancies between classically recognized taxa and the observed relationships
      at the order, family and genus levels; these inconsistencies question underlying
      hypotheses regarding the evolution of certain morphological characters.
      Therefore, we extended the available taxa and character set by sequencing the
      complete small subunit (SSU) rDNA and the almost complete large subunit (LSU)
      rDNA of additional key species and complemented this dataset by substantially
      increasing the length of available LSU sequences. Phylogenetic analyses provided
      new hypotheses about the relationships of Calcarea and about the evolution of
      certain morphological characters. We tested our phylogeny against competing
      phylogenetic hypotheses presented by previous classification systems. Our data
      reject the current order-level classification by again finding non-monophyletic
      Leucosolenida, Clathrinida and Murrayonida. In the subclass Calcinea, we
      recovered a clade that includes all species with a cortex, which is largely
      consistent with the previously proposed order Leucettida. Other orders that had
      been rejected in the current system were not found, but could not be rejected in
      our tests either. We found several additional families and genera polyphyletic:
      the families Leucascidae and Leucaltidae and the genus Leucetta in Calcinea, and
      in Calcaronea the family Amphoriscidae and the genus Ute. Our phylogeny also
      provided support for the vaguely suspected close relationship of several members
      of Grantiidae with giantortical diactines to members of Heteropiidae. Similarly,
      our analyses revealed several unexpected affinities, such as a sister group
      relationship between Leucettusa (Leucaltidae) and Leucettidae and between
      Leucascandra (Jenkinidae) and Sycon carteri (Sycettidae). According to our
      results, the taxonomy of Calcarea is in desperate need of a thorough revision,
      which cannot be achieved by considering morphology alone or relying on a taxon
      sampling based on the current classification below the subclass level.

PMID- 22479396
TI  - Approximate invariance of metabolic energy per synapse during development in
      mammalian brains.
AB  - During mammalian development the cerebral metabolic rate correlates qualitatively
      with synaptogenesis, and both often exhibit bimodal temporal profiles. Despite
      these non-monotonic dependencies, it is found based on empirical data for
      different mammals that regional metabolic rate per synapse is approximately
      conserved from birth to adulthood for a given species (with a slight deviation
      from this constancy for human visual and temporal cortices during adolescence). A
      typical synapse uses about (7+/-2)*10(3) glucose molecules per second in primate
      cerebral cortex, and about five times of that amount in cat and rat visual
      cortices. A theoretical model for brain metabolic expenditure is used to estimate
      synaptic signaling and neural spiking activity during development. It is found
      that synaptic efficacy is generally inversely correlated with average firing
      rate, and, additionally, synapses consume a bulk of metabolic energy, roughly 50
      90% during most of the developmental process (except human temporal cortex <
      50%). Overall, these results suggest a tight regulation of brain electrical and
      chemical activities during the formation and consolidation of neural connections.
      This presumably reflects strong energetic constraints on brain development.

PMID- 22479397
TI  - Inhibition of SIRT1 impairs the accumulation and transcriptional activity of HIF
      1alpha protein under hypoxic conditions.
AB  - Sirtuins and hypoxia-inducible transcription factors (HIF) have well-established
      roles in regulating cellular responses to metabolic and oxidative stress. Recent
      reports have linked these two protein families by demonstrating that sirtuins can
      regulate the activity of HIF-1 and HIF-2. Here we investigated the role of SIRT1,
      a NAD+-dependent deacetylase, in the regulation of HIF-1 activity in hypoxic
      conditions. Our results show that in hepatocellular carcinoma (HCC) cell lines,
      hypoxia did not alter SIRT1 mRNA or protein expression, whereas it predictably
      led to the accumulation of HIF-1alpha and the up-regulation of its target genes.
      In hypoxic models in vitro and in in vivo models of systemic hypoxia and
      xenograft tumor growth, knockdown of SIRT1 protein with shRNA or inhibition of
      its activity with small molecule inhibitors impaired the accumulation of HIF
      1alpha protein and the transcriptional increase of its target genes. In addition,
      endogenous SIRT1 and HIF-1alpha proteins co-immunoprecipitated and loss of SIRT1
      activity led to a hyperacetylation of HIF-1alpha. Taken together, our data
      suggest that HIF-1alpha and SIRT1 proteins interact in HCC cells and that HIF
      1alpha is a target of SIRT1 deacetylase activity. Moreover, SIRT1 is necessary
      for HIF-1alpha protein accumulation and activation of HIF-1 target genes under
      hypoxic conditions.

PMID- 22479398
TI  - An ancient pathway combining carbon dioxide fixation with the generation and
      utilization of a sodium ion gradient for ATP synthesis.
AB  - Synthesis of acetate from carbon dioxide and molecular hydrogen is considered to
      be the first carbon assimilation pathway on earth. It combines carbon dioxide
      fixation into acetyl-CoA with the production of ATP via an energized cell
      membrane. How the pathway is coupled with the net synthesis of ATP has been an
      enigma. The anaerobic, acetogenic bacterium Acetobacterium woodii uses an ancient
      version of this pathway without cytochromes and quinones. It generates a sodium
      ion potential across the cell membrane by the sodium-motive ferredoxin:NAD
      oxidoreductase (Rnf). The genome sequence of A. woodii solves the enigma: it
      uncovers Rnf as the only ion-motive enzyme coupled to the pathway and unravels a
      metabolism designed to produce reduced ferredoxin and overcome energetic barriers
      by virtue of electron-bifurcating, soluble enzymes.

PMID- 22479399
TI  - Analysis of the subunit stoichiometries in viral entry.
AB  - Virions of the Human Immunodeficiency Virus (HIV) infect cells by first attaching
      with their surface spikes to the CD4 receptor on target cells. This leads to
      conformational changes in the viral spikes, enabling the virus to engage a
      coreceptor, commonly CCR5 or CXCR4, and consecutively to insert the fusion
      peptide into the cellular membrane. Finally, the viral and the cellular membranes
      fuse. The HIV spike is a trimer consisting of three identical heterodimers
      composed of the gp120 and gp41 envelope proteins. Each of the gp120 proteins in
      the trimer is capable of attaching to the CD4 receptor and the coreceptor, and
      each of the three gp41 units harbors a fusion domain. It is still under debate
      how many of the envelope subunits within a given trimer have to bind to the CD4
      receptors and to the coreceptors, and how many gp41 protein fusion domains are
      required for fusion. These numbers are referred to as subunit stoichiometries. We
      present a mathematical framework for estimating these parameters individually by
      analyzing infectivity assays with pseudotyped viruses. We find that the number of
      spikes that are engaged in mediating cell entry and the distribution of the spike
      number play important roles for the estimation of the subunit stoichiometries.
      Our model framework also shows why it is important to subdivide the question of
      the number of functional subunits within one trimer into the three different
      subunit stoichiometries. In a second step, we extend our models to study whether
      the subunits within one trimer cooperate during receptor binding and fusion. As
      an example for how our models can be applied, we reanalyze a data set on subunit
      stoichiometries. We find that two envelope proteins have to engage with CD4
      receptors and coreceptors and that two fusion proteins must be revealed within
      one trimer for viral entry. Our study is motivated by the mechanism of HIV entry
      but the experimental technique and the model framework can be extended to other
      viral systems as well.

PMID- 22479400
TI  - Modulation by endothelin-1 of spontaneous activity and membrane currents of
      atrioventricular node myocytes from the rabbit heart.
AB  - BACKGROUND: The atrioventricular node (AVN) is a key component of the cardiac
      pacemaker-conduction system. Although it is known that receptors for the peptide
      hormone endothelin-1 (ET-1) are expressed in the AVN, there is very little
      information available on the modulatory effects of ET-1 on AVN electrophysiology.
      This study characterises for the first time acute modulatory effects of ET-1 on
      AVN cellular electrophysiology. METHODS: Electrophysiological experiments were
      conducted in which recordings were made from rabbit isolated AVN cells at 35-37
      degrees C using the whole-cell patch clamp recording technique. RESULTS:
      Application of ET-1 (10 nM) to spontaneously active AVN cells led rapidly (within
      ~13 s) to membrane potential hyperpolarisation and cessation of spontaneous
      action potentials (APs). This effect was prevented by pre-application of the
      ET(A) receptor inhibitor BQ-123 (1 uM) and was not mimicked by the ET(B) receptor
      agonist IRL-1620 (300 nM). In whole-cell voltage-clamp experiments, ET-1
      partially inhibited L-type calcium current (I(Ca,L)) and rapid delayed rectifier
      K(+) current (I(Kr)), whilst it transiently activated the hyperpolarisation
      activated current (I(f)) at voltages negative to the pacemaking range, and
      activated an inwardly rectifying current that was inhibited by both tertiapin-Q
      (300 nM) and Ba(2+) ions (2 mM); each of these effects was sensitive to ET(A)
      receptor inhibition. In cells exposed to tertiapin-Q, ET-1 application did not
      produce membrane potential hyperpolarisation or immediate cessation of
      spontaneous activity; instead, there was a progressive decline in AP amplitude
      and depolarisation of maximum diastolic potential. CONCLUSIONS: Acutely applied
      ET-1 exerts a direct modulatory effect on AVN cell electrophysiology. The
      dominant effect of ET-1 in this study was activation of a tertiapin-Q sensitive
      inwardly rectifying K(+) current via ET(A) receptors, which led rapidly to cell
      quiescence.

PMID- 22479401
TI  - Genes are often sheltered from the global histone hyperacetylation induced by
      HDAC inhibitors.
AB  - Histone deacetylase inhibitors (HDACi) are increasingly used as therapeutic
      agents, but the mechanisms by which they alter cell behaviour remain unclear.
      Here we use microarray expression analysis to show that only a small proportion
      of genes (~9%) have altered transcript levels after treating HL60 cells with
      different HDACi (valproic acid, Trichostatin A, suberoylanilide hydroxamic acid).
      Different gene populations respond to each inhibitor, with as many genes down- as
      up-regulated. Surprisingly, HDACi rarely induced increased histone acetylation at
      gene promoters, with most genes examined showing minimal change, irrespective of
      whether genes were up- or down-regulated. Many genes seem to be sheltered from
      the global histone hyperacetyation induced by HDACi.

PMID- 22479402
TI  - A method for removal of low frequency components associated with head movements
      from dual-axis swallowing accelerometry signals.
AB  - Head movements can greatly affect swallowing accelerometry signals. In this
      paper, we implement a spline-based approach to remove low frequency components
      associated with these motions. Our approach was tested using both synthetic and
      real data. Synthetic signals were used to perform a comparative analysis of the
      spline-based approach with other similar techniques. Real data, obtained data
      from 408 healthy participants during various swallowing tasks, was used to
      analyze the processing accuracy with and without the spline-based head motions
      removal scheme. Specifically, we analyzed the segmentation accuracy and the
      effects of the scheme on statistical properties of these signals, as measured by
      the scaling analysis. The results of the numerical analysis showed that the
      spline-based technique achieves a superior performance in comparison to other
      existing techniques. Additionally, when applied to real data, we improved the
      accuracy of the segmentation process by achieving a 27% drop in the number of
      false negatives and a 30% drop in the number of false positives. Furthermore, the
      anthropometric trends in the statistical properties of these signals remained
      unaltered as shown by the scaling analysis, but the strength of statistical
      persistence was significantly reduced. These results clearly indicate that any
      future medical devices based on swallowing accelerometry signals should remove
      head motions from these signals in order to increase segmentation accuracy.

PMID- 22479403
TI  - 3D Traction forces in cancer cell invasion.
AB  - Cell invasion through a dense three-dimensional (3D) matrix is believed to depend
      on the ability of cells to generate traction forces. To quantify the role of cell
      tractions during invasion in 3D, we present a technique to measure the elastic
      strain energy stored in the matrix due to traction-induced deformations. The
      matrix deformations around a cell were measured by tracking the 3D positions of
      fluorescent beads tightly embedded in the matrix. The bead positions served as
      nodes for a finite element tessellation. From the strain in each element and the
      known matrix elasticity, we computed the local strain energy in the matrix
      surrounding the cell. We applied the technique to measure the strain energy of
      highly invasive MDA-MB-231 breast carcinoma and A-125 lung carcinoma cells in
      collagen gels. The results were compared to the strain energy generated by non
      invasive MCF-7 breast and A-549 lung carcinoma cells. In all cases, cells locally
      contracted the matrix. Invasive breast and lung carcinoma cells showed a
      significantly higher contractility compared to non-invasive cells. Higher
      contractility, however, was not universally associated with higher invasiveness.
      For instance, non-invasive A-431 vulva carcinoma cells were the most contractile
      cells among all cell lines tested. As a universal feature, however, we found that
      invasive cells assumed an elongated spindle-like morphology as opposed to a more
      spherical shape of non-invasive cells. Accordingly, the distribution of strain
      energy density around invasive cells followed patterns of increased complexity
      and anisotropy. These results suggest that not so much the magnitude of traction
      generation but their directionality is important for cancer cell invasion.

PMID- 22479404
TI  - LILRA2 selectively modulates LPS-mediated cytokine production and inhibits
      phagocytosis by monocytes.
AB  - The activating immunoglobulin-like receptor, subfamily A, member 2 (LILRA2) is
      primarily expressed on the surface of cells of the innate immunity including
      monocytes, macrophages, neutrophils, basophils and eosinophils but not on
      lymphocytes and NK cells. LILRA2 cross-linking on monocytes induces pro
      inflammatory cytokines while inhibiting dendritic cell differentiation and
      antigen presentation. A similar activating receptor, LILRA4, has been shown to
      modulate functions of TLR7/9 in dendritic cells. These suggest a selective immune
      regulatory role for LILRAs during innate immune responses. However, whether
      LILRA2 has functions distinct from other receptors of the innate immunity
      including Toll-like receptor (TLR) 4 and FcgammaRI remains unknown. Moreover, the
      effects of LILRA2 on TLR4 and FcgammaRI-mediated monocyte functions are not
      elucidated. Here, we show activation of monocytes via LILRA2 cross-linking
      selectively increased GM-CSF production but failed to induce IL-12 and MCP-1
      production that were strongly up-regulated by LPS, suggesting functions distinct
      from TLR4. Interestingly, LILRA2 cross-linking on monocytes induced similar
      amounts of IL-6, IL-8, G-CSF and MIP-1alpha but lower levels of TNFalpha, IL
      1beta, IL-10 and IFNgamma compared to those stimulated with LPS. Furthermore,
      cross-linking of LILRA2 on monocytes significantly decreased phagocytosis of IgG
      coated micro-beads and serum opsonized Escherichia coli but had limited effect on
      phagocytosis of non-opsonized bacteria. Simultaneous co-stimulation of monocytes
      through LILRA2 and LPS or sequential activation of monocytes through LILRA2
      followed by LPS led lower levels of TNFalpha, IL-1beta and IL-12 production
      compared to LPS alone, but had additive effect on levels of IL-10 and IFNgamma
      but not on IL-6. Interestingly, LILRA2 cross-linking on monocytes caused
      significant inhibition of TLR4 mRNA and protein, suggesting LILRA2-mediated
      suppression of LPS responses might be partly via regulation of this receptor.
      Taken together, we provide evidence that LILRA2-mediated activation of monocytes
      is significantly different to LPS and that LILRA2 selectively modulates LPS
      mediated monocyte activation and FcgammaRI-dependent phagocytosis.

PMID- 22479405
TI  - Characterization of the interaction of full-length HIV-1 Vif protein with its key
      regulator CBFbeta and CRL5 E3 ubiquitin ligase components.
AB  - Human immunodeficiency virus-1 (HIV-1) viral infectivity factor (Vif) is
      essential for viral replication because of its ability to eliminate the host's
      antiviral response to HIV-1 that is mediated by the APOBEC3 family of cellular
      cytidine deaminases. Vif targets these proteins, including APOBEC3G, for
      polyubiquitination and subsequent proteasome-mediated degradation via the
      formation of a Cullin5-ElonginB/C-based E3 ubiquitin ligase. Determining how the
      cellular components of this E3 ligase complex interact with Vif is critical to
      the intelligent design of new antiviral drugs. However, structural studies of
      Vif, both alone and in complex with cellular partners, have been hampered by an
      inability to express soluble full-length Vif protein. Here we demonstrate that a
      newly identified host regulator of Vif, core-binding factor-beta (CBFbeta),
      interacts directly with Vif, including various isoforms and a truncated form of
      this regulator. In addition, carboxyl-terminal truncations of Vif lacking the BC
      box and cullin box motifs were sufficient for CBFbeta interaction. Furthermore,
      association of Vif with CBFbeta, alone or in combination with Elongin B/C
      (EloB/C), greatly increased the solubility of full-length Vif. Finally, a stable
      complex containing Vif-CBFbeta-EloB/C was purified in large quantity and shown to
      bind purified Cullin5 (Cul5). This efficient strategy for purifying Vif-Cul5
      CBFbeta-EloB/C complexes will facilitate future structural and biochemical
      studies of Vif function and may provide the basis for useful screening approaches
      for identifying novel anti-HIV drug candidates.

PMID- 22479406
TI  - HlSRB, a Class B scavenger receptor, is key to the granulocyte-mediated microbial
      phagocytosis in ticks.
AB  - Ixodid ticks transmit various pathogens of deadly diseases to humans and animals.
      However, the specific molecule that functions in the recognition and control of
      pathogens inside ticks is not yet to be identified. Class B scavenger receptor
      CD36 (SRB) participates in internalization of apoptotic cells, certain bacterial
      and fungal pathogens, and modified low-density lipoproteins. Recently, we have
      reported on recombinant HlSRB, a 50-kDa protein with one hydrophobic SRB domain
      from the hard tick, Haemaphysalis longicornis. Here, we show that HlSRB plays
      vital roles in granulocyte-mediated phagocytosis to invading Escherichia coli and
      contributes to the first-line host defense against various pathogens. Data
      clearly revealed that granulocytes that up-regulated the expression of cell
      surface HlSRB are almost exclusively involved in hemocyte-mediated phagocytosis
      for E. coli in ticks, and post-transcriptional silencing of the HlSRB-specific
      gene ablated the granulocytes' ability to phagocytose E. coli and resulted in the
      mortality of ticks due to high bacteremia. This is the first report demonstrating
      that a scavenger receptor molecule contributes to hemocyte-mediated phagocytosis
      against exogenous pathogens, isolated and characterized from hematophagous
      arthropods.

PMID- 22479407
TI  - Estimating fitness by competition assays between drug susceptible and resistant
      Mycobacterium tuberculosis of predominant lineages in Mumbai, India.
AB  - BACKGROUND: Multi Drug Resistant Tuberculosis (MDR TB) is a threat to global
      tuberculosis control. A significant fitness cost has been associated with DR
      strains from specific lineages. Evaluation of the influence of the competing drug
      susceptible strains on fitness of drug resistant strains may have an important
      bearing on understanding the spread of MDR TB. The aim of this study was to
      evaluate the fitness of MDR TB strains, from a TB endemic region of western
      India: Mumbai, belonging to 3 predominant lineages namely CAS, Beijing and MANU
      in the presence of drug susceptible strains from the same lineages. METHODOLOGY:
      Drug susceptible strains from a single lineage were mixed with drug resistant
      strain, bearing particular non synonymous mutation (rpoB D516V; inhA, A16G; katG,
      S315T1/T2) from the same or different lineages. Fitness of M.tuberculosis (M.tb)
      strains was evaluated using the difference in growth rates obtained by using the
      CFU assay system. CONCLUSION/SIGNIFICANCE: While MANU were most fit amongst the
      drug susceptible strains of the 3 lineages, only Beijing MDR strains were found
      to grow in the presence of any of the competing drug susceptible strains. A
      disproportionate increase in Beijing MDR could be an alarm for an impending
      epidemic in this locale. In addition to particular non synonymous substitutions,
      the competing strains in an environment may impact the fitness of circulating
      drug resistant strains.

PMID- 22479408
TI  - Carbohydrate recognition by an architecturally complex alpha-N
      acetylglucosaminidase from Clostridium perfringens.
AB  - CpGH89 is a large multimodular enzyme produced by the human and animal pathogen
      Clostridium perfringens. The catalytic activity of this exo-alpha-D-N
      acetylglucosaminidase is directed towards a rare carbohydrate motif, N-acetyl
      beta-D-glucosamine-alpha-1,4-D-galactose, which is displayed on the class III
      mucins deep within the gastric mucosa. In addition to the family 89 glycoside
      hydrolase catalytic module this enzyme has six modules that share sequence
      similarity to the family 32 carbohydrate-binding modules (CBM32s), suggesting the
      enzyme has considerable capacity to adhere to carbohydrates. Here we suggest that
      two of the modules, CBM32-1 and CBM32-6, are not functional as carbohydrate
      binding modules (CBMs) and demonstrate that three of the CBMs, CBM32-3, CBM32-4,
      and CBM32-5, are indeed capable of binding carbohydrates. CBM32-3 and CBM32-4
      have a novel binding specificity for N-acetyl-beta-D-glucosamine-alpha-1,4-D
      galactose, which thus complements the specificity of the catalytic module. The X
      ray crystal structure of CBM32-4 in complex with this disaccharide reveals a mode
      of recognition that is based primarily on accommodation of the unique bent shape
      of this sugar. In contrast, as revealed by a series of X-ray crystal structures
      and quantitative binding studies, CBM32-5 displays the structural and functional
      features of galactose binding that is commonly associated with CBM family 32. The
      functional CBM32s that CpGH89 contains suggest the possibility for multivalent
      binding events and the partitioning of this enzyme to highly specific regions
      within the gastrointestinal tract.

PMID- 22479409
TI  - Formal modeling and analysis of the MAL-associated biological regulatory network:
      insight into cerebral malaria.
AB  - The discrete modeling formalism of Rene Thomas is a well known approach for the
      modeling and analysis of Biological Regulatory Networks (BRNs). This formalism
      uses a set of parameters which reflect the dynamics of the BRN under study. These
      parameters are initially unknown but may be deduced from the appropriately chosen
      observed dynamics of a BRN. The discrete model can be further enriched by using
      the model checking tool HyTech along with delay parameters. This paves the way to
      accurately analyse a BRN and to make predictions about critical trajectories
      which lead to a normal or diseased response. In this paper, we apply the formal
      discrete and hybrid (discrete and continuous) modeling approaches to characterize
      behavior of the BRN associated with MyD88-adapter-like (MAL)--a key protein
      involved with innate immune response to infections. In order to demonstrate the
      practical effectiveness of our current work, different trajectories and
      corresponding conditions that may lead to the development of cerebral malaria
      (CM) are identified. Our results suggest that the system converges towards
      hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active
      along with pre-existing high cytokine levels which may play an important role in
      CM pathogenesis.

PMID- 22479410
TI  - Iron-responsive olfactory uptake of manganese improves motor function deficits
      associated with iron deficiency.
AB  - Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting
      that toxicity related to manganese exposure could be modified by iron status. To
      explore possible interactions, the distribution of intranasally-instilled
      manganese in control and iron-deficient rat brain was characterized by
      quantitative image analysis using T1-weighted magnetic resonance imaging (MRI).
      Manganese accumulation in the brain of iron-deficient rats was doubled after
      intranasal administration of MnCl(2) for 1- or 3-week. Enhanced manganese level
      was observed in specific brain regions of iron-deficient rats, including the
      striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced
      time on a standard accelerating rotarod bar before falling and with lower peak
      speed compared to controls; unexpectedly, these measures of motor function
      significantly improved in iron-deficient rats intranasally-instilled with
      MnCl(2). Although tissue dopamine concentrations were similar in the striatum,
      dopamine transporter (DAT) and dopamine receptor D(1) (D1R) levels were reduced
      and dopamine receptor D(2) (D2R) levels were increased in manganese-instilled
      rats, suggesting that manganese-induced changes in post-synaptic dopaminergic
      signaling contribute to the compensatory effect. Enhanced olfactory manganese
      uptake during iron deficiency appears to be a programmed "rescue response" with
      beneficial influence on motor impairment due to low iron status.

PMID- 22479411
TI  - Underrepresentation of elderly people in randomised controlled trials. The
      example of trials of 4 widely prescribed drugs.
AB  - BACKGROUND: We aimed to determine the representation of elderly people in
      published reports of randomized controlled trials (RCTs). We focused on trials of
      4 medications--pioglitazone, rosuvastatin, risedronate, and valsartan-frequently
      used by elderly patients with chronic medical conditions. METHODS AND FINDINGS:
      We selected all reports of RCTs indexed in PubMed from 1966 to April 2008
      evaluating one of the 4 medications of interest. Estimates of the community-based
      "on-treatment" population were from a national health insurance database (SNIIR
      AM) covering approximately 86% of the population in France. From this database,
      we evaluated data claims from January 2006 to December 2007 for 1,958,716
      patients who received one of the medications of interest for more than 6 months.
      Of the 155 RCT reports selected, only 3 studies were exclusively of elderly
      patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%)
      for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for
      rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged
      65 or older was within or above that treated in clinical practice. In 62.2% of
      the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and
      70.2% for valsartan, the proportion of patients aged 65 or older was lower than
      half that in the treated population. The representation of elderly people did not
      differ by publication date or sample size. CONCLUSIONS: Elderly patients are
      poorly represented in RCTs of drugs they are likely to receive.

PMID- 22479412
TI  - Computational characterization of 3' splice variants in the GFAP isoform family.
AB  - Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein
      specific to central nervous system (CNS) astrocytes. It has been the subject of
      intense interest due to its association with neurodegenerative diseases, and
      because of growing evidence that IF proteins not only modulate cellular
      structure, but also cellular function. Moreover, GFAP has a family of splicing
      isoforms apparently more complex than that of other CNS IF proteins, consistent
      with it possessing a range of functional and structural roles. The gene consists
      of 9 exons, and to date all isoforms associated with 3' end splicing have been
      identified from modifications within intron 7, resulting in the generation of
      exon 7a (GFAPdelta/epsilon) and 7b (GFAPkappa). To better understand the nature
      and functional significance of variation in this region, we used a Bayesian
      multiple change-point approach to identify conserved regions. This is the first
      successful application of this method to a single gene--it has previously only
      been used in whole-genome analyses. We identified several highly or moderately
      conserved regions throughout the intron 7/7a/7b regions, including untranslated
      regions and regulatory features, consistent with the biology of GFAP. Several
      putative unconfirmed features were also identified, including a possible new
      isoform. We then integrated multiple computational analyses on both the DNA and
      protein sequences from the mouse, rat and human, showing that the major isoform,
      GFAPalpha, has highly conserved structure and features across the three species,
      whereas the minor isoforms GFAPdelta/epsilon and GFAPkappa have low conservation
      of structure and features at the distal 3' end, both relative to each other and
      relative to GFAPalpha. The overall picture suggests distinct and tightly
      regulated functions for the 3' end isoforms, consistent with complex astrocyte
      biology. The results illustrate a computational approach for characterising
      splicing isoform families, using both DNA and protein sequences.

PMID- 22479413
TI  - Productive infection of bovine papillomavirus type 2 in the placenta of pregnant
      cows affected with urinary bladder tumors.
AB  - Papillomaviruses (PVs) are believed to be highly epitheliotropic as they usually
      establish productive infections within stratified epithelia. In vitro, various
      PVs appear to complete their entire life-cycle in different trophoblastic cell
      lines. In this study, infection by and protein expression of bovine
      papillomavirus type 2 (BPV-2) in the uterine and chorionic epithelium of the
      placenta has been described in four cows suffering from naturally occurring
      papillomavirus-associated urothelial bladder tumors. E5 oncoprotein was detected
      both by Western blot analysis and immunohistochemically. It appears to be
      complexed and perfectly co-localized with the activated platelet-derived growth
      factor beta receptor (PDGFbetaR) by laser scanning confocal microscopy. The
      activated PDGFbetaR might be involved in organogenesis and neo-angiogenesis
      rather than in cell transformation during pregnancy. The major capsid protein,
      L1, believed to be only expressed in productive papillomavirus infection has been
      detected by Western blot analysis. Immunohistochemical investigations confirmed
      the presence of L1 protein both in the cytoplasm and nuclei of cells of the
      uterine and chorionic epithelium. Trophoblastic cells appear to be the major
      target for L1 protein expression. Finally, the early protein E2, required for
      viral DNA replication and known to be expressed during a productive infection,
      has been detected by Western blot and immunohistochemically. Electron microscopic
      investigations detected viral particles in nuclei of uterine and chorionic
      epithelium. This study shows that both active and productive infections by BPV-2
      in the placenta of pregnant cows can occur in vivo.

PMID- 22479414
TI  - Internalization and down-regulation of the ALK receptor in neuroblastoma cell
      lines upon monoclonal antibodies treatment.
AB  - Recently, activating mutations of the full length ALK receptor, with two hot
      spots at positions F1174 and R1275, have been characterized in sporadic cases of
      neuroblastoma. Here, we report similar basal patterns of ALK phosphorylation
      between the neuroblastoma IMR-32 cell line, which expresses only the wild-type
      receptor (ALK(WT)), and the SH-SY5Y cell line, which exhibits a heterozygous ALK
      F1174L mutation and expresses both ALK(WT) and ALK(F1174L) receptors. We
      demonstrate that this lack of detectable increased phosphorylation in SH-SY5Y
      cells is a result of intracellular retention and proteasomal degradation of the
      mutated receptor. As a consequence, in SH-SY5Y cells, plasma membrane appears
      strongly enriched for ALK(WT) whereas both ALK(WT) and ALK(F1174L) were present
      in intracellular compartments. We further explored ALK receptor trafficking by
      investigating the effect of agonist and antagonist mAb (monoclonal antibodies) on
      ALK internalization and down-regulation, either in SH-SY5Y cells or in cells
      expressing only ALK(WT). We observe that treatment with agonist mAbs resulted in
      ALK internalization and lysosomal targeting for receptor degradation. In
      contrast, antagonist mAb induced ALK internalization and recycling to the plasma
      membrane. Importantly, we correlate this differential trafficking of ALK in
      response to mAb with the recruitment of the ubiquitin ligase Cbl and ALK
      ubiquitylation only after agonist stimulation. This study provides novel insights
      into the mechanisms regulating ALK trafficking and degradation, showing that
      various ALK receptor pools are regulated by proteasome or lysosome pathways
      according to their intracellular localization.

PMID- 22479415
TI  - Small heat shock protein alphaA-crystallin prevents photoreceptor degeneration in
      experimental autoimmune uveitis.
AB  - The small heat shock protein, alphaA-crystallin null (alphaA-/-) mice are known
      to be more prone to retinal degeneration than the wild type mice in Experimental
      Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous
      administration of alphaA preserves retinal architecture and prevents
      photoreceptor damage in EAU. Interestingly, only alphaA and not alphaB-crystallin
      (alphaB), a closely related small heat shock protein works, pointing to molecular
      specificity in the observed retinal protection. The possible involvement of
      alphaA in retinal protection through immune modulation is corroborated by
      adaptive transfer experiments, (employing alphaA-/- and wild type mice with EAU
      as donors and Rag2-/- as the recipient mice), which indicate that alphaA protects
      against the autoimmune challenge by modulating the systemic B and T cell
      immunity. We show that alphaA administration causes marked reduction in Th1
      cytokines (TNF-alpha, IL-12 and IFN-gamma), both in the retina and in the spleen;
      notably, IL-17 was only reduced in the retina suggesting local intervention.
      Importantly, expression of Toll-like receptors and their associated adaptors is
      also inhibited suggesting that alphaA protection, against photoreceptor loss in
      EAU, is associated with systemic suppression of both the adaptive and innate
      immune responses.

PMID- 22479416
TI  - Risk-return relationship in a complex adaptive system.
AB  - For survival and development, autonomous agents in complex adaptive systems
      involving the human society must compete against or collaborate with others for
      sharing limited resources or wealth, by using different methods. One method is to
      invest, in order to obtain payoffs with risk. It is a common belief that
      investments with a positive risk-return relationship (namely, high risk high
      return and vice versa) are dominant over those with a negative risk-return
      relationship (i.e., high risk low return and vice versa) in the human society;
      the belief has a notable impact on daily investing activities of investors. Here
      we investigate the risk-return relationship in a model complex adaptive system,
      in order to study the effect of both market efficiency and closeness that exist
      in the human society and play an important role in helping to establish
      traditional finance/economics theories. We conduct a series of computer-aided
      human experiments, and also perform agent-based simulations and theoretical
      analysis to confirm the experimental observations and reveal the underlying
      mechanism. We report that investments with a negative risk-return relationship
      have dominance over those with a positive risk-return relationship instead in
      such a complex adaptive systems. We formulate the dynamical process for the
      system's evolution, which helps to discover the different role of identical and
      heterogeneous preferences. This work might be valuable not only to complexity
      science, but also to finance and economics, to management and social science, and
      to physics.

PMID- 22479417
TI  - Functional analysis of general odorant binding protein 2 from the meadow moth,
      Loxostege sticticalis L. (Lepidoptera: Pyralidae).
AB  - Odorant binding proteins play a crucial role in transporting semiochemicals
      across the sensillum lymph to olfactory receptors within the insect antennal
      sensilla. In this study, the general odorant binding protein 2 gene was cloned
      from the antennae of Loxostege sticticalis, using reverse transcription PCR and
      rapid amplification of cDNA ends. Recombinant LstiGOBP2 was expressed in
      Escherichia coli and purified by Ni ion affinity chromatography. Real-time PCR
      assays indicated that LstiGOBP2 mRNA is expressed mainly in adult antennae, with
      expression levels differing with developmental age. Ligand-binding experiments
      using N-phenyl-naphthylamine (1-NPN) as a fluorescent probe demonstrated that the
      LstiGOBP2 protein has binding affinity to a broad range of odorants. Most
      importantly, trans-11-tetradecen-1-yl acetate, the pheromone component of
      Loxostege sticticalis, and trans-2-hexenal and cis-3-hexen-1-ol, the most
      abundant plant volatiles in essential oils extracted from host plants, had high
      binding affinities to LstiGOBP2 and elicited strong electrophysiological
      responses from the antennae of adults.

PMID- 22479418
TI  - Proteomic profiling and protein identification by MALDI-TOF mass spectrometry in
      unsequenced parasitic nematodes.
AB  - Lack of genomic sequence data and the relatively high cost of tandem mass
      spectrometry have hampered proteomic investigations into helminths, such as
      resolving the mechanism underpinning globally reported anthelmintic resistance.
      Whilst detailed mechanisms of resistance remain unknown for the majority of drug
      parasite interactions, gene mutations and changes in gene and protein expression
      are proposed key aspects of resistance. Comparative proteomic analysis of drug
      resistant and -susceptible nematodes may reveal protein profiles reflecting drug
      related phenotypes. Using the gastro-intestinal nematode, Haemonchus contortus as
      case study, we report the application of freely available expressed sequence tag
      (EST) datasets to support proteomic studies in unsequenced nematodes. EST
      datasets were translated to theoretical protein sequences to generate a
      searchable database. In conjunction with matrix-assisted laser desorption
      ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), Peptide Mass
      Fingerprint (PMF) searching of databases enabled a cost-effective protein
      identification strategy. The effectiveness of this approach was verified in
      comparison with MS/MS de novo sequencing with searching of the same EST protein
      database and subsequent searches of the NCBInr protein database using the Basic
      Local Alignment Search Tool (BLAST) to provide protein annotation. Of 100
      proteins from 2-DE gel spots, 62 were identified by MALDI-TOF-MS and PMF
      searching of the EST database. Twenty randomly selected spots were analysed by
      electrospray MS/MS and MASCOT Ion Searches of the same database. The resulting
      sequences were subjected to BLAST searches of the NCBI protein database to
      provide annotation of the proteins and confirm concordance in protein identity
      from both approaches. Further confirmation of protein identifications from the
      MS/MS data were obtained by de novo sequencing of peptides, followed by FASTS
      algorithm searches of the EST putative protein database. This study demonstrates
      the cost-effective use of available EST databases and inexpensive, accessible
      MALDI-TOF MS in conjunction with PMF for reliable protein identification in
      unsequenced organisms.

PMID- 22479419
TI  - Genome-wide association study of treatment refractory schizophrenia in Han
      Chinese.
AB  - We report the first genome-wide association study of a joint analysis using 795
      Han Chinese individuals with treatment-refractory schizophrenia (TRS) and 806
      controls. Three loci showed suggestive significant association with TRS were
      identified. These loci include: rs10218843 (P = 3.04 * 10(-7)) and rs11265461 (P
      = 1.94 * 10(-7)) are adjacent to signaling lymphocytic activation molecule family
      member 1 (SLAMF1); rs4699030 (P = 1.94 * 10(-6)) and rs230529 (P = 1.74 * 10(-7))
      are located in the gene nuclear factor of kappa light polypeptide gene enhancer
      in B-cells 1 (NFKB1); and rs13049286 (P = 3.05 * 10(-5)) and rs3827219 (P = 1.66
      * 10(-5)) fall in receptor-interacting serine/threonine-protein kinase 4 (RIPK4).
      One isolated single nucleotide polymorphism (SNP), rs739617 (P = 3.87 * 10(-5))
      was also identified to be associated with TRS. The -94delATTG allele (rs28362691)
      located in the promoter region of NFKB1 was identified by resequencing and was
      found to associate with TRS (P = 4.85 * 10(-6)). The promoter assay demonstrated
      that the -94delATTG allele had a significant lower promoter activity than the 
      94insATTG allele in the SH-SY5Y cells. This study suggests that rs28362691 in
      NFKB1 might be involved in the development of TRS.

PMID- 22479420
TI  - Ligation tunes protein reactivity in an ancient haemoglobin: kinetic evidence for
      an allosteric mechanism in Methanosarcina acetivorans protoglobin.
AB  - Protoglobin from Methanosarcina acetivorans (MaPgb) is a dimeric globin with
      peculiar structural properties such as a completely buried haem and two
      orthogonal tunnels connecting the distal cavity to the solvent. CO binding to and
      dissociation from MaPgb occur through a biphasic kinetics. We show that the
      heterogenous kinetics arises from binding to (and dissociation from) two tertiary
      conformations in ligation-dependent equilibrium. Ligation favours the species
      with high binding rate (and low dissociation rate). The equilibrium is shifted
      towards the species with low binding (and high dissociation) rates for the
      unliganded molecules. A quantitative model is proposed to describe the observed
      carbonylation kinetics.

PMID- 22479421
TI  - Colorization and automated segmentation of human T2 MR brain images for
      characterization of soft tissues.
AB  - Characterization of tissues like brain by using magnetic resonance (MR) images
      and colorization of the gray scale image has been reported in the literature,
      along with the advantages and drawbacks. Here, we present two independent
      methods; (i) a novel colorization method to underscore the variability in brain
      MR images, indicative of the underlying physical density of bio tissue, (ii) a
      segmentation method (both hard and soft segmentation) to characterize gray brain
      MR images. The segmented images are then transformed into color using the above
      mentioned colorization method, yielding promising results for manual tracing. Our
      color transformation incorporates the voxel classification by matching the
      luminance of voxels of the source MR image and provided color image by measuring
      the distance between them. The segmentation method is based on single-phase
      clustering for 2D and 3D image segmentation with a new auto centroid selection
      method, which divides the image into three distinct regions (gray matter (GM),
      white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical
      knowledge). Results have been successfully validated on human T2-weighted (T2)
      brain MR images. The proposed method can be potentially applied to gray-scale
      images from other imaging modalities, in bringing out additional diagnostic
      tissue information contained in the colorized image processing approach as
      described.

PMID- 22479422
TI  - Bagging statistical network inference from large-scale gene expression data.
AB  - Modern biology and medicine aim at hunting molecular and cellular causes of
      biological functions and diseases. Gene regulatory networks (GRN) inferred from
      gene expression data are considered an important aid for this research by
      providing a map of molecular interactions. Hence, GRNs have the potential
      enabling and enhancing basic as well as applied research in the life sciences. In
      this paper, we introduce a new method called BC3NET for inferring causal gene
      regulatory networks from large-scale gene expression data. BC3NET is an ensemble
      method that is based on bagging the C3NET algorithm, which means it corresponds
      to a Bayesian approach with noninformative priors. In this study we demonstrate
      for a variety of simulated and biological gene expression data from S. cerevisiae
      that BC3NET is an important enhancement over other inference methods that is
      capable of capturing biochemical interactions from transcription regulation and
      protein-protein interaction sensibly. An implementation of BC3NET is freely
      available as an R package from the CRAN repository.

PMID- 22479423
TI  - Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an
      EPR site-directed spin-labeling and relaxation study.
AB  - The second messenger lipid PIP(3) (phosphatidylinositol-3,4,5-trisphosphate) is
      generated by the lipid kinase PI3K (phosphoinositide-3-kinase) in the inner
      leaflet of the plasma membrane, where it regulates a broad array of cell
      processes by recruiting multiple signaling proteins containing PIP(3)-specific
      pleckstrin homology (PH) domains to the membrane surface. Despite the broad
      importance of PIP(3)-specific PH domains, the membrane docking geometry of a PH
      domain bound to its target PIP(3) lipid on a bilayer surface has not yet been
      experimentally determined. The present study employs EPR site-directed spin
      labeling and relaxation methods to elucidate the membrane docking geometry of
      GRP1 PH domain bound to bilayer-embedded PIP(3). The model target bilayer
      contains the neutral background lipid PC and both essential targeting lipids: (i)
      PIP(3) target lipid that provides specificity and affinity, and (ii) PS
      facilitator lipid that enhances the PIP(3) on-rate via an electrostatic search
      mechanism. The EPR approach measures membrane depth parameters for 18 function
      retaining spin labels coupled to the PH domain, and for calibration spin labels
      coupled to phospholipids. The resulting depth parameters, together with the known
      high resolution structure of the co-complex between GRP1 PH domain and the PIP(3)
      headgroup, provide sufficient constraints to define an optimized, self-consistent
      membrane docking geometry. In this optimized geometry the PH domain engulfs the
      PIP(3) headgroup with minimal bilayer penetration, yielding the shallowest
      membrane position yet described for a lipid binding domain. This binding
      interaction displaces the PIP(3) headgroup from its lowest energy position and
      orientation in the bilayer, but the headgroup remains within its energetically
      accessible depth and angular ranges. Finally, the optimized docking geometry
      explains previous biophysical findings including mutations observed to disrupt
      membrane binding, and the rapid lateral diffusion observed for PIP(3)-bound GRP1
      PH domain on supported lipid bilayers.

PMID- 22479424
TI  - X4 Human immunodeficiency virus type 1 gp120 promotes human hepatic stellate cell
      activation and collagen I expression through interactions with CXCR4.
AB  - BACKGROUND & AIMS: Patients coinfected with HIV-1 and HCV develop more rapid
      liver fibrosis than patients monoinfected with HCV. HIV RNA levels correlate with
      fibrosis progression implicating HIV directly in the fibrotic process. While
      activated hepatic stellate cells (HSCs) express the 2 major HIV chemokine
      coreceptors, CXCR4 and CCR5, little is known about the pro-fibrogenic effects of
      the HIV-1 envelope protein, gp120, on HSCs. We therefore examined the in vitro
      impact of X4 gp120 on HSC activation, collagen I expression, and underlying
      signaling pathways and examined the in vivo expression of gp120 in HIV/HCV
      coinfected livers. METHODS: Primary human HSCs and LX-2 cells, a human HSC line,
      were challenged with X4 gp120 and expression of fibrogenic markers assessed by
      qRT-PCR and Western blot +/- either CXCR4-targeted shRNA or anti-CXCR4
      neutralizing antibody. Downstream intracellular signaling pathways were evaluated
      with Western blot and pre-treatment with specific pathway inhibitors. Gp120
      immunostaining was performed on HIV/HCV coinfected liver biopsies. RESULTS: X4 gp
      120 significantly increased expression of alpha-smooth muscle actin (a-SMA) and
      collagen I in HSCs which was blocked by pre-incubation with either CXCR4-targeted
      shRNA or anti-CXCR4 neutralizing antibody. Furthermore, X4 gp120 promoted
      Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and pretreatment
      with an ERK inhibitor attenuated HSC activation and collagen I expression.
      Sinusoidal staining for gp120 was evident in HIV/HCV coinfected livers.
      CONCLUSIONS: X4 HIV-1 gp120 is pro-fibrogenic through its interactions with CXCR4
      on activated HSCs. The availability of small molecule inhibitors to CXCR4 make
      this a potential anti-fibrotic target in HIV/HCV coinfected patients.

PMID- 22479425
TI  - Cortactin tyrosine phosphorylation promotes its deacetylation and inhibits cell
      spreading.
AB  - BACKGROUND: Cortactin is a classical Src kinase substrate that participates in
      actin cytoskeletal dynamics by activating the Arp2/3 complex and interacting with
      other regulatory proteins, including FAK. Cortactin has various domains that may
      contribute to the assembly of different protein platforms to achieve process
      specificity. Though the protein is known to be regulated by post-translational
      modifications such as phosphorylation and acetylation, how tyrosine
      phosphorylation regulates cortactin activity is poorly understood. Since the
      basal level of tyrosine phosphorylation is low, this question must be studied
      using stimulated cell cultures, which are physiologically relevant but unreliable
      and difficult to work with. In fact, their unreliability may be the cause of some
      contradictory findings about the dynamics of tyrosine phosphorylation of
      cortactin in different processes. METHODOLOGY/PRINCIPAL FINDINGS: In the present
      study, we try to overcome these problems by using a Functional Interaction Trap
      (FIT) system, which involves cotransfecting cells with a kinase (Src) and a
      target protein (cortactin), both of which are fused to complementary leucine
      zipper domains. The FIT system allowed us to control precisely the tyrosine
      phosphorylation of cortactin and explore its relationship with cortactin
      acetylation. CONCLUSIONS/SIGNIFICANCE: Using this system, we provide definitive
      evidence that a competition exists between acetylation and tyrosine
      phosphorylation of cortactin and that phosphorylation inhibits cell spreading. We
      confirmed the results from the FIT system by examining endogenous cortactin in
      different cell types. Furthermore, we demonstrate that cell spreading promotes
      the association of cortactin and FAK and that tyrosine phosphorylation of
      cortactin disrupts this interaction, which may explain how it inhibits cell
      spreading.

PMID- 22479426
TI  - Mirna expression profiles identify drivers in colorectal and pancreatic cancers.
AB  - BACKGROUND AND AIM: Altered expression of microRNAs (miRNAs) hallmarks many
      cancer types. The study of the associations of miRNA expression profile and
      cancer phenotype could help identify the links between deregulation of miRNA
      expression and oncogenic pathways. METHODS: Expression profiling of 866 human
      miRNAs in 19 colorectal and 17 pancreatic cancers and in matched adjacent normal
      tissues was investigated. Classical paired t-test and random forest analyses were
      applied to identify miRNAs associated with tissue-specific tumors. Network
      analysis based on a computational approach to mine associations between cancer
      types and miRNAs was performed. RESULTS: The merge between the two statistical
      methods used to intersect the miRNAs differentially expressed in colon and
      pancreatic cancers allowed the identification of cancer-specific miRNA
      alterations. By miRNA-network analysis, tissue-specific patterns of miRNA
      deregulation were traced: the driving miRNAs were miR-195, miR-1280, miR-140-3p
      and miR-1246 in colorectal tumors, and miR-103, miR-23a and miR-15b in pancreatic
      cancers. CONCLUSION: MiRNA expression profiles may identify cancer-specific
      signatures and potentially useful biomarkers for the diagnosis of tissue specific
      cancers. miRNA-network analysis help identify altered miRNA regulatory networks
      that could play a role in tumor pathogenesis.

PMID- 22479427
TI  - Loss of PTEN is not associated with poor survival in newly diagnosed glioblastoma
      patients of the temozolomide era.
AB  - INTRODUCTION: Pre-temozolomide studies demonstrated that loss of the tumor
      suppressor gene PTEN held independent prognostic significance in GBM patients. We
      investigated whether loss of PTEN predicted shorter survival in the temozolomide
      era. The role of PTEN in the PI3K/Akt pathway is also reviewed. METHODS: Patients
      with histologically proven newly diagnosed GBM were identified from a
      retrospective database between 2007 and 2010. Cox proportional hazards analysis
      was used to calculate the independent effects of PTEN expression, age, extent of
      resection, Karnofsky performance scale (KPS), and treatment on overall survival.
      RESULTS: Sixty-five percent of patients were men with median age of 63 years, and
      70% had KPS>=80. Most patients (81%) received standard treatment (temozolomide
      with concurrent radiation). A total of 72 (47%) patients had retained PTEN
      expression. Median overall survival (OS) was 19.1 months (95% CI: 15.0-22.5).
      Median survival of 20.0 months (95% CI: 15.0-25.5) and 18.2 months (95% CI: 13.0
      25.7) was observed in PTEN retained and PTEN loss patients, respectively (p =
      .71). PTEN loss patients were also found to have amplifications of EGFR gene more
      frequently than patients with retained PTEN (70.8% vs. 47.8%, p = .01).
      Multivariate analysis showed that older age (HR 1.64, CI: 1.02-2.63, p = .04),
      low KPS (HR 3.57, CI: 2.20-5.79, p<.0001), and lack of standard treatment (HR
      3.98, CI: 2.38-6.65, p<.0001) yielded worse survival. PTEN loss was not
      prognostic of overall survival (HR 1.31, CI: 0.85-2.03, p = .22). CONCLUSIONS:
      Loss of expression of PTEN does not confer poor overall survival in the
      temozolomide era. These findings imply a complex and non-linear molecular
      relationship between PTEN, its regulators and effectors in the tumorigenesis of
      glioblastoma. Additionally, there is evidence that temozolomide may be more
      effective in eradicating GBM cancer cells with PTEN loss and hence, level the
      outcomes between the PTEN retained and loss groups.

PMID- 22479428
TI  - Achieving secondary prevention low-density lipoprotein particle concentration
      goals using lipoprotein cholesterol-based data.
AB  - BACKGROUND: Epidemiologic studies suggest that LDL particle concentration (LDL-P)
      may remain elevated at guideline recommended LDL cholesterol goals, representing
      a source of residual risk. We examined the following seven separate lipid
      parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk
      secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a
      composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL
      and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non
      HDL-C<130, TG<150; LDL phenotype; HDL-C >= 40; TG<150; and TG/HDL-C<3. METHODS:
      We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR
      lipoprotein particle concentration in 148 unselected primary and secondary
      prevention patients. RESULTS: TC/HDL-C<3 effectively discriminated subjects by
      LDL-P goal (F = 84.1, p<10(-6)). The ATP-III very high risk composite target (LDL
      C<70, nonHDL-C<100, TG<150) was also effective (F = 42.8, p<10(-5)). However, the
      standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150) was
      also effective but yielded higher LDL-P than the very high risk composite (F =
      42.0, p<10(-5)) with upper 95% confidence interval of LDL-P less than 1000
      nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects
      but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F =
      15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively). LDL density phenotype
      neared significance (F = 2.85, p = 0.094) and the HDL-C cutpoint of 40 mg/dL did
      not discriminate (F = 0.53, p = 0.47) alone or add discriminatory power to ATP
      III targets. CONCLUSIONS: A simple composite of ATP-III very high risk
      lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most
      effectively identified subjects meeting the secondary prevention target level of
      LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in
      many clinical circumstances.

PMID- 22479429
TI  - Regular health checks: cross-sectional survey.
AB  - OBJECTIVE: To investigate whether Danish providers of general health checks
      present a balanced account of possible benefits and harms on their websites and
      whether the health checks are evidence-based. METHODS AND DESIGN: Cross-sectional
      study. The search engines Google and Jubii (Danish) were in July and August 2009
      used to identify 56 websites using Danish search terms for "health check" and
      "health examination". The content of the websites were evaluated using a
      checklist with 15 officially recommended information items. All tests offered
      through the websites were registered. The evidence for tests offered through at
      least 10% of the websites was identified in structured searches using PubMed and
      The Cochrane Library. RESULTS: We found 36 different tests on 56 websites
      offering health checks. Twenty one tests were offered on at least 10% of the
      websites. Seventeen (81%) of these tests were unsupported by evidence, or there
      was evidence against them for screening purposes. We found evidence supporting
      screening using body-mass-index, blood pressure, cholesterol, and faecal occult
      blood testing. None of the websites mentioned possible risks or harms. The
      websites presented a median of 1 of the 15 information items; the highest number
      from any provider was 2. CONCLUSIONS: Information from Danish providers of health
      checks was sparse and tests were often offered against existing evidence or
      despite lack of evidence. None of the included websites mentioned potential risks
      or harms.

PMID- 22479430
TI  - A 3D image filter for parameter-free segmentation of macromolecular structures
      from electron tomograms.
AB  - 3D image reconstruction of large cellular volumes by electron tomography (ET) at
      high (<= 5 nm) resolution can now routinely resolve organellar and compartmental
      membrane structures, protein coats, cytoskeletal filaments, and macromolecules.
      However, current image analysis methods for identifying in situ macromolecular
      structures within the crowded 3D ultrastructural landscape of a cell remain labor
      intensive, time-consuming, and prone to user-bias and/or error. This paper
      demonstrates the development and application of a parameter-free, 3D
      implementation of the bilateral edge-detection (BLE) algorithm for the rapid and
      accurate segmentation of cellular tomograms. The performance of the 3D BLE filter
      has been tested on a range of synthetic and real biological data sets and
      validated against current leading filters-the pseudo 3D recursive and Canny
      filters. The performance of the 3D BLE filter was found to be comparable to or
      better than that of both the 3D recursive and Canny filters while offering the
      significant advantage that it requires no parameter input or optimisation. Edge
      widths as little as 2 pixels are reproducibly detected with signal intensity and
      grey scale values as low as 0.72% above the mean of the background noise. The 3D
      BLE thus provides an efficient method for the automated segmentation of complex
      cellular structures across multiple scales for further downstream processing,
      such as cellular annotation and sub-tomogram averaging, and provides a valuable
      tool for the accurate and high-throughput identification and annotation of 3D
      structural complexity at the subcellular level, as well as for mapping the
      spatial and temporal rearrangement of macromolecular assemblies in situ within
      cellular tomograms.

PMID- 22479431
TI  - Risk factors and outcomes of candidemia caused by biofilm-forming isolates in a
      tertiary care hospital.
AB  - BACKGROUND: Very few data exist on risk factors for developing biofilm-forming
      Candida bloodstream infection (CBSI) or on variables associated with the outcome
      of patients treated for this infection. METHODS AND FINDINGS: We identified 207
      patients with CBSI, from whom 84 biofilm-forming and 123 non biofilm-forming
      Candida isolates were recovered. A case-case-control study to identify risk
      factors and a cohort study to analyze outcomes were conducted. In addition, two
      sub-groups of case patients were analyzed after matching for age, sex, APACHE III
      score, and receipt of adequate antifungal therapy. Independent predictors of
      biofilm-forming CBSI were presence of central venous catheter (odds ratio [OR],
      6.44; 95% confidence interval [95% CI], 3.21-12.92) or urinary catheter (OR,
      2.40; 95% CI, 1.18-4.91), use of total parenteral nutrition (OR, 5.21; 95% CI,
      2.59-10.48), and diabetes mellitus (OR, 4.47; 95% CI, 2.03-9.83). Hospital
      mortality, post-CBSI hospital length of stay (LOS) (calculated only among
      survivors), and costs of antifungal therapy were significantly greater among
      patients infected by biofilm-forming isolates than those infected by non-biofilm
      forming isolates. Among biofilm-forming CBSI patients receiving adequate
      antifungal therapy, those treated with highly active anti-biofilm (HAAB) agents
      (e.g., caspofungin) had significantly shorter post-CBSI hospital LOS than those
      treated with non-HAAB antifungal agents (e.g., fluconazole); this difference was
      confirmed when this analysis was conducted only among survivors. After matching,
      all the outcomes were still favorable for patients with non-biofilm-forming CBSI.
      Furthermore, the biofilm-forming CBSI was significantly associated with a matched
      excess risk for hospital death of 1.77 compared to non-biofilm-forming CBSI.
      CONCLUSIONS: Our data show that biofilm growth by Candida has an adverse impact
      on clinical and economic outcomes of CBSI. Of note, better outcomes were seen for
      those CBSI patients who received HAAB antifungal therapy.

PMID- 22479433
TI  - Significant communities in large sparse networks.
AB  - Researchers use community-detection algorithms to reveal large-scale organization
      in biological and social networks, but community detection is useful only if the
      communities are significant and not a result of noisy data. To assess the
      statistical significance of the network communities, or the robustness of the
      detected structure, one approach is to perturb the network structure by removing
      links and measure how much the communities change. However, perturbing sparse
      networks is challenging because they are inherently sensitive; they shatter
      easily if links are removed. Here we propose a simple method to perturb sparse
      networks and assess the significance of their communities. We generate resampled
      networks by adding extra links based on local information, then we aggregate the
      information from multiple resampled networks to find a coarse-grained description
      of significant clusters. In addition to testing our method on benchmark networks,
      we use our method on the sparse network of the European Court of Justice (ECJ)
      case law, to detect significant and insignificant areas of law. We use our
      significance analysis to draw a map of the ECJ case law network that reveals the
      relations between the areas of law.

PMID- 22479432
TI  - How the emotional content of discourse affects language comprehension.
AB  - Emotion effects on cognition have often been reported. However, only few studies
      investigated emotional effects on subsequent language processing, and in most
      cases these effects were induced by non-linguistic stimuli such as films, faces,
      or pictures. Here, we investigated how a paragraph of positive, negative, or
      neutral emotional valence affects the processing of a subsequent emotionally
      neutral sentence, which contained either semantic, syntactic, or no violation,
      respectively, by means of event-related brain potentials (ERPs). Behavioral data
      revealed strong effects of emotion; error rates and reaction times increased
      significantly in sentences preceded by a positive paragraph relative to negative
      and neutral ones. In ERPs, the N400 to semantic violations was not affected by
      emotion. In the syntactic experiment, however, clear emotion effects were
      observed on ERPs. The left anterior negativity (LAN) to syntactic violations,
      which was not visible in the neutral condition, was present in the negative and
      positive conditions. This is interpreted as reflecting modulatory effects of
      prior emotions on syntactic processing, which is discussed in the light of three
      alternative or complementary explanations based on emotion-induced cognitive
      styles, working memory, and arousal models. The present effects of emotion on the
      LAN are especially remarkable considering that syntactic processing has often
      been regarded as encapsulated and autonomous.

PMID- 22479434
TI  - Membrane fusion and cell entry of XMRV are pH-independent and modulated by the
      envelope glycoprotein's cytoplasmic tail.
AB  - Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus that
      was originally identified from human prostate cancer patients and subsequently
      linked to chronic fatigue syndrome. Recent studies showed that XMRV is a
      recombinant mouse retrovirus; hence, its association with human diseases has
      become questionable. Here, we demonstrated that XMRV envelope (Env)-mediated
      pseudoviral infection is not blocked by lysosomotropic agents and cellular
      protease inhibitors, suggesting that XMRV entry is not pH-dependent. The full
      length XMRV Env was unable to induce syncytia formation and cell-cell fusion,
      even in cells overexpressing the viral receptor, XPR1. However, truncation of the
      C-terminal 21 or 33 amino acid residues in the cytoplasmic tail (CT) of XMRV Env
      induced substantial membrane fusion, not only in the permissive 293 cells but
      also in the nonpermissive CHO cells that lack a functional XPR1 receptor. The
      increased fusion activities of these truncations correlated with their enhanced
      SU shedding into culture media, suggesting conformational changes in the
      ectodomain of XMRV Env. Noticeably, further truncation of the CT of XMRV Env
      proximal to the membrane-spanning domain severely impaired the Env fusogenicity,
      as well as dramatically decreased the Env incorporations into MoMLV
      oncoretroviral and HIV-1 lentiviral vectors resulting in greatly reduced viral
      transductions. Collectively, our studies reveal that XMRV entry does not require
      a low pH or low pH-dependent host proteases, and that the cytoplasmic tail of
      XMRV Env critically modulates membrane fusion and cell entry. Our data also imply
      that additional cellular factors besides XPR1 are likely to be involved in XMRV
      entry.

PMID- 22479435
TI  - Stable isotope biogeochemistry of seabird guano fertilization: results from
      growth chamber studies with maize (Zea mays).
AB  - BACKGROUND: Stable isotope analysis is being utilized with increasing regularity
      to examine a wide range of issues (diet, habitat use, migration) in ecology,
      geology, archaeology, and related disciplines. A crucial component to these
      studies is a thorough understanding of the range and causes of baseline isotopic
      variation, which is relatively poorly understood for nitrogen (delta(15)N).
      Animal excrement is known to impact plant delta(15)N values, but the effects of
      seabird guano have not been systematically studied from an agricultural or
      horticultural standpoint. METHODOLOGY/PRINCIPAL FINDINGS: This paper presents
      isotopic (delta(13)C and delta(15)N) and vital data for maize (Zea mays)
      fertilized with Peruvian seabird guano under controlled conditions. The level of
      (15)N enrichment in fertilized plants is very large, with delta(15)N values
      ranging between 25.5 and 44.70/00 depending on the tissue and amount of
      fertilizer applied; comparatively, control plant delta(15)N values ranged between
      -0.3 and 5.70/00. Intraplant and temporal variability in delta(15)N values were
      large, particularly for the guano-fertilized plants, which can be attributed to
      changes in the availability of guano-derived N over time, and the reliance of
      stored vs. absorbed N. Plant delta(13)C values were not significantly impacted by
      guano fertilization. High concentrations of seabird guano inhibited maize
      germination and maize growth. Moreover, high levels of seabird guano greatly
      impacted the N metabolism of the plants, resulting in significantly higher tissue
      N content, particularly in the stalk. CONCLUSIONS/SIGNIFICANCE: The results
      presented in this study demonstrate the very large impact of seabird guano on
      maize delta(15)N values. The use of seabird guano as a fertilizer can thus be
      traced using stable isotope analysis in food chemistry applications
      (certification of organic inputs). Furthermore, the fertilization of maize with
      seabird guano creates an isotopic signature very similar to a high-trophic level
      marine resource, which must be considered when interpreting isotopic data from
      archaeological material.

PMID- 22479436
TI  - Viral sequence variation in chronic carriers of hepatitis C virus has a low
      impact on liver steatosis.
AB  - Most clinical studies suggest that the prevalence and severity of liver steatosis
      are higher in patients infected with hepatitis C virus (HCV) genotype 3 than in
      patients infected with other genotypes. This may reflect the diversity and
      specific intrinsic properties of genotype 3 virus proteins. We analyzed the
      possible association of particular residues of the HCV core and NS5A proteins
      known to dysregulate lipid metabolism with steatosis severity in the livers of
      patients chronically infected with HCV. We used transmission electron microscopy
      to quantify liver steatosis precisely in a group of 27 patients, 12 of whom were
      infected with a genotype 3 virus, the other 15 being infected with viruses of
      other genotypes. We determined the area covered by lipid droplets in liver
      tissues and analyzed the diversity of the core and NS5A regions encoded by the
      viral variants circulating in these patients. The area covered by lipid droplets
      did not differ significantly between patients infected with genotype 3 viruses
      and those infected with other genotypes. The core and NS5A protein sequences of
      the viral variants circulating in patients with mild or severe steatosis were
      evenly distributed throughout the phylogenic trees established from all the
      collected sequences. Thus, individual host factors seem to play a much greater
      role than viral factors in the development of severe steatosis in patients
      chronically infected with HCV, including those infected with genotype 3 viruses.

PMID- 22479437
TI  - A chemical screen probing the relationship between mitochondrial content and cell
      size.
AB  - The cellular content of mitochondria changes dynamically during development and
      in response to external stimuli, but the underlying mechanisms remain obscure. To
      systematically identify molecular probes and pathways that control mitochondrial
      abundance, we developed a high-throughput imaging assay that tracks both the per
      cell mitochondrial content and the cell size in confluent human umbilical vein
      endothelial cells. We screened 28,786 small molecules and observed that hundreds
      of small molecules are capable of increasing or decreasing the cellular content
      of mitochondria in a manner proportionate to cell size, revealing stereotyped
      control of these parameters. However, only a handful of compounds dissociate this
      relationship. We focus on one such compound, BRD6897, and demonstrate through
      secondary assays that it increases the cellular content of mitochondria as
      evidenced by fluorescence microscopy, mitochondrial protein content, and
      respiration, even after rigorous correction for cell size, cell volume, or total
      protein content. BRD6897 increases uncoupled respiration 1.6-fold in two
      different, non-dividing cell types. Based on electron microscopy, BRD6897 does
      not alter the percent of cytoplasmic area occupied by mitochondria, but instead,
      induces a striking increase in the electron density of existing mitochondria. The
      mechanism is independent of known transcriptional programs and is likely to be
      related to a blockade in the turnover of mitochondrial proteins. At present the
      molecular target of BRD6897 remains to be elucidated, but if identified, could
      reveal an important additional mechanism that governs mitochondrial biogenesis
      and turnover.

PMID- 22479438
TI  - Real-time visualization and quantitation of vascular permeability in vivo:
      implications for drug delivery.
AB  - The leaky, heterogeneous vasculature of human tumors prevents the even
      distribution of systemic drugs within cancer tissues. However, techniques for
      studying vascular delivery systems in vivo often require complex mammalian models
      and time-consuming, surgical protocols. The developing chicken embryo is a well
      established model for human cancer that is easily accessible for tumor imaging.
      To assess this model for the in vivo analysis of tumor permeability, human tumors
      were grown on the chorioallantoic membrane (CAM), a thin vascular membrane which
      overlays the growing chick embryo. The real-time movement of small fluorescent
      dextrans through the tumor vasculature and surrounding tissues were used to
      measure vascular leak within tumor xenografts. Dextran extravasation within tumor
      sites was selectively enhanced an interleukin-2 (IL-2) peptide fragment or
      vascular endothelial growth factor (VEGF). VEGF treatment increased vascular leak
      in the tumor core relative to surrounding normal tissue and increased doxorubicin
      uptake in human tumor xenografts. This new system easily visualizes vascular
      permeability changes in vivo and suggests that vascular permeability may be
      manipulated to improve chemotherapeutic targeting to tumors.

PMID- 22479439
TI  - Stroke outcomes in Malawi, a country with high prevalence of HIV: a prospective
      follow-up study.
AB  - BACKGROUND: Stroke contributes significantly to disability and mortality in
      developing countries yet little is known about the determinants of stroke
      outcomes in such countries. 12% of Malawian adults have HIV/AIDS. It is not known
      whether having HIV-infection alters the outcome of stroke. The aim of this study
      was to document the functional outcome and mortality at 1 year of first-ever
      acute stroke in Malawi. Also to find out if the baseline variables, including HIV
      infection, affect the outcome of stroke. METHODS AND FINDINGS: 147 adult patients
      with first-ever acute stroke were prospectively followed up for 12 months.
      Conventional risk factors and HIV-infection were assessed at baseline. Stroke
      severity was evaluated with modified National Institute of Health Stroke Scale
      (mNIHSS) and functional outcome with modified Rankin scale (mRS). Fifty (34%) of
      patients were HIV-seropositive. 53.4% of patients had a poor outcome (severe
      disability or death, mRS 4-6) at 1 year. Poor outcome was related to stroke
      severity and female gender but not to presence of HIV-infection. HIV-seropositive
      patients were younger and had less often common risk factors for stroke. They
      suffer more often ischemic stroke than HIV-seronegative patients. CONCLUSIONS:
      Mild stroke and male gender were associated with favourable outcome. HIV
      infection is common in stroke patients in Malawi but does not worsen the outcome
      of stroke. However, it may be a risk factor for ischemic stroke for young people,
      who do not have the common stroke risk factors. Our results are significant,
      because stroke outcome in HIV-seropositive patients has not been studied before
      in a setting such as ours, with very limited resources and a high prevalence of
      HIV.

PMID- 22479440
TI  - The transcriptome and proteome of the diatom Thalassiosira pseudonana reveal a
      diverse phosphorus stress response.
AB  - Phosphorus (P) is a critical driver of phytoplankton growth and ecosystem
      function in the ocean. Diatoms are an abundant class of marine phytoplankton that
      are responsible for significant amounts of primary production. With the control
      they exert on the oceanic carbon cycle, there have been a number of studies
      focused on how diatoms respond to limiting macro and micronutrients such as iron
      and nitrogen. However, diatom physiological responses to P deficiency are poorly
      understood. Here, we couple deep sequencing of transcript tags and quantitative
      proteomics to analyze the diatom Thalassiosira pseudonana grown under P-replete
      and P-deficient conditions. A total of 318 transcripts were differentially
      regulated with a false discovery rate of <0.05, and a total of 136 proteins were
      differentially abundant (p<0.05). Significant changes in the abundance of
      transcripts and proteins were observed and coordinated for multiple biochemical
      pathways, including glycolysis and translation. Patterns in transcript and
      protein abundance were also linked to physiological changes in cellular P
      distributions, and enzyme activities. These data demonstrate that diatom P
      deficiency results in changes in cellular P allocation through polyphosphate
      production, increased P transport, a switch to utilization of dissolved organic P
      through increased production of metalloenzymes, and a remodeling of the cell
      surface through production of sulfolipids. Together, these findings reveal that
      T. pseudonana has evolved a sophisticated response to P deficiency involving
      multiple biochemical strategies that are likely critical to its ability to
      respond to variations in environmental P availability.

PMID- 22479441
TI  - A demonstration of 'broken' visual space.
AB  - It has long been assumed that there is a distorted mapping between real and
      'perceived' space, based on demonstrations of systematic errors in judgements of
      slant, curvature, direction and separation. Here, we have applied a direct test
      to the notion of a coherent visual space. In an immersive virtual environment,
      participants judged the relative distance of two squares displayed in separate
      intervals. On some trials, the virtual scene expanded by a factor of four between
      intervals although, in line with recent results, participants did not report any
      noticeable change in the scene. We found that there was no consistent depth
      ordering of objects that can explain the distance matches participants made in
      this environment (e.g. A>B>D yet also A<C<D) and hence no single one-to-one
      mapping between participants' perceived space and any real 3D environment.
      Instead, factors that affect pairwise comparisons of distances dictate
      participants' performance. These data contradict, more directly than previous
      experiments, the idea that the visual system builds and uses a coherent internal
      3D representation of a scene.

PMID- 22479442
TI  - Measuring straight line segments using HT butterflies.
AB  - This paper addresses the features of Hough Transform (HT) butterflies suitable
      for image-based segment detection and measurement. The full segment parameters
      such as the position, slope, width, length, continuity, and uniformity are
      related to the features of the HT butterflies. Mathematical analysis and
      experimental data are presented in order to demonstrate and build the
      relationship between the measurements of segments and the features of HT
      butterflies. An effective method is subsequently proposed to employ these
      relationships in order to discover the parameters of segments. Power line
      inspection is considered as an application of the proposed method. The
      application demonstrates that the proposed method is effective for power line
      inspection, especially for corner detection when they cross poles.

PMID- 22479443
TI  - Denial of reward in the neonate shapes sociability and serotonergic activity in
      the adult rat.
AB  - BACKGROUND: Manipulations of the early environment are linked to long-lasting
      alterations of emotionality and social capabilities. Denial of rewarding mother
      pup interactions in early life of rats could serve as model for child neglect.
      Negative consequences for social competence in later life, accompanied by changes
      in the serotonergic system would be expected. In contrast, rewarding mother-pup
      contact should promote adequate social abilities. METHODOLOGY/PRINCIPAL FINDINGS:
      Male Wistar rats trained in a T-maze during postnatal days 10-13 under denial
      (DER) or permission (RER) of maternal contact were tested for play behavior in
      adolescence and for coping with defeat in adulthood. We estimated serotonin (5
      HT) levels in the brain under basal conditions and following defeat, as well as
      serotonin receptor 1A (5-HT1A) and serotonin transporter (SERT) expression. DER
      rats exhibited increased aggressive-like play behavior in adolescence (i.e.
      increased nape attacks, p<0.0001) and selected a proactive coping style during
      defeat in adulthood (higher sum of proactive behaviors: number of attacks,
      flights, rearings and defensive upright posture; p = 0.011, p<0.05 vs RER, non
      handled-NH). In adulthood, they had lower 5-HT levels in both the prefrontal
      cortex (p<0.05 vs RER) and the amygdala (p<0.05 vs NH), increased 5-HT levels
      following defeat (PFC p<0.0001) and decreased serotonin turnover (amygdala p =
      0.008). The number of 5-HT1A immunopositive cells in the CA1 hippocampal area was
      increased (p<0.05 DER, vs RER, NH); SERT levels in the amygdala were elevated
      (p<0.05 vs RER, NH), but were lower in the prefrontal cortex (p<0.05 vs NH).
      CONCLUSIONS/SIGNIFICANCE: Denial of expected maternal reward early in life
      negatively affects sociability and the serotonergic system in a complex manner.
      We propose that our animal model could contribute to the identification of the
      neurobiological correlates of early neglect effects on social behavior and coping
      with challenges, but also in parallel with the effects of a rewarding early-life
      environment.

PMID- 22479444
TI  - Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that
      modulate central nervous system autoimmunity.
AB  - Laquinimod is a novel oral drug that is currently being evaluated for the
      treatment of relapsing-remitting (RR) multiple sclerosis (MS). Using the animal
      model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we
      examined how laquinimod promotes immune modulation. Oral laquinimod treatment
      reversed established RR-EAE and was associated with reduced central nervous
      system (CNS) inflammation, decreased Th1 and Th17 responses, and an increase in
      regulatory T cells (Treg). In vivo laquinimod treatment inhibited donor myelin
      specific T cells from transferring EAE to naive recipient mice. In vivo
      laquinimod treatment altered subpopulations of myeloid antigen presenting cells
      (APC) that included a decrease in CD11c(+)CD11b(+)CD4(+) dendritic cells (DC) and
      an elevation of CD11b(hi)Gr1(hi) monocytes. CD11b(+) cells from these mice
      exhibited an anti-inflammatory type II phenotype characterized by reduced STAT1
      phosphorylation, decreased production of IL-6, IL-12/23 and TNF, and increased IL
      10. In adoptive transfer, donor type II monocytes from laquinimod-treated mice
      suppressed clinical and histologic disease in recipients with established EAE. As
      effects were observed in both APC and T cell compartments, we examined whether T
      cell immune modulation occurred as a direct effect of laquinimod on T cells, or
      as a consequence of altered APC function. Inhibition of Th1 and Th17
      differentiation was observed only when type II monocytes or DC from laquinimod
      treated mice were used as APC, regardless of whether myelin-specific T cells were
      obtained from laquinimod-treated or untreated mice. Thus, laquinimod modulates
      adaptive T cell immune responses via its effects on cells of the innate immune
      system, and may not influence T cells directly.

PMID- 22479445
TI  - Practical application of methanol-mediated mutualistic symbiosis between
      Methylobacterium species and a roof greening moss, Racomitrium japonicum.
AB  - Bryophytes, or mosses, are considered the most maintenance-free materials for
      roof greening. Racomitrium species are most often used due to their high
      tolerance to desiccation. Because they grow slowly, a technology for forcing
      their growth is desired. We succeeded in the efficient production of R. japonicum
      in liquid culture. The structure of the microbial community is crucial to
      stabilize the culture. A culture-independent technique revealed that the cultures
      contain methylotrophic bacteria. Using yeast cells that fluoresce in the presence
      of methanol, methanol emission from the moss was confirmed, suggesting that it is
      an important carbon and energy source for the bacteria. We isolated
      Methylobacterium species from the liquid culture and studied their
      characteristics. The isolates were able to strongly promote the growth of some
      mosses including R. japonicum and seed plants, but the plant-microbe combination
      was important, since growth promotion was not uniform across species. One of the
      isolates, strain 22A, was cultivated with R. japonicum in liquid culture and in a
      field experiment, resulting in strong growth promotion. Mutualistic symbiosis can
      thus be utilized for industrial moss production.

PMID- 22479446
TI  - Reconstructing viral genomes from the environment using fosmid clones: the case
      of haloviruses.
AB  - BACKGROUND: Metaviriomes, the viral genomes present in an environment, have been
      studied by direct sequencing of the viral DNA or by cloning in small insert
      libraries. The short reads generated by both approaches make it very difficult to
      assemble and annotate such flexible genomic entities. Many environmental viruses
      belong to unknown groups or prey on uncultured and little known cellular
      lineages, and hence might not be present in databases. METHODOLOGY AND PRINCIPAL
      FINDINGS: Here we have used a different approach, the cloning of viral DNA into
      fosmids before sequencing, to obtain natural contigs that are close to the size
      of a viral genome. We have studied a relatively low diversity extreme
      environment: saturated NaCl brines, which simplifies the analysis and
      interpretation of the data. Forty-two different viral genomes were retrieved, and
      some of these were almost complete, and could be tentatively identified as head
      tail phages (Caudovirales). CONCLUSIONS AND SIGNIFICANCE: We found a cluster of
      phage genomes that most likely infect Haloquadratum walsbyi, the square archaeon
      and major component of the community in these hypersaline habitats. The identity
      of the prey could be confirmed by the presence of CRISPR spacer sequences shared
      by the virus and one of the available strain genomes. Other viral clusters
      detected appeared to prey on the Nanohaloarchaea and on the bacterium
      Salinibacter ruber, covering most of the diversity of microbes found in this type
      of environment. This approach appears then as a viable alternative to describe
      metaviriomes in a much more detailed and reliable way than by the more common
      approaches based on direct sequencing. An example of transfer of a CRISPR cluster
      including repeats and spacers was accidentally found supporting the dynamic
      nature and frequent transfer of this peculiar prokaryotic mechanism of cell
      protection.

PMID- 22479447
TI  - Progenitor-derivative relationships of Hordeum polyploids (Poaceae, Triticeae)
      inferred from sequences of TOPO6, a nuclear low-copy gene region.
AB  - Polyploidization is a major mechanism of speciation in plants. Within the barley
      genus Hordeum, approximately half of the taxa are polyploids. While for diploid
      species a good hypothesis of phylogenetic relationships exists, there is little
      information available for the polyploids (4*, 6*) of Hordeum. Relationships among
      all 33 diploid and polyploid Hordeum species were analyzed with the low-copy
      nuclear marker region TOPO6 for 341 Hordeum individuals and eight outgroup
      species. PCR products were either directly sequenced or cloned and on average 12
      clones per individual were included in phylogenetic analyses. In most diploid
      Hordeum species TOPO6 is probably a single-copy locus. Most sequences found in
      polyploid individuals phylogenetically cluster together with sequences derived
      from diploid species and thus allow the identification of parental taxa of
      polyploids. Four groups of sequences occurring only in polyploid taxa are
      interpreted as footprints of extinct diploid taxa, which contributed to
      allopolyploid evolution. Our analysis identifies three key species involved in
      the evolution of the American polyploids of the genus. (i) All but one of the
      American tetraploids have a TOPO6 copy originating from the Central Asian diploid
      H. roshevitzii, the second copy clustering with different American diploid
      species. (ii) All hexaploid species from the New World have a copy of an extinct
      close relative of H. californicum and (iii) possess the TOPO6 sequence pattern of
      tetraploid H. jubatum, each with an additional copy derived from different
      American diploids. Tetraploid H. bulbosum is an autopolyploid, while the assumed
      autopolyploid H. brevisubulatum (4*, 6*) was identified as allopolyploid
      throughout most of its distribution area. The use of a proof-reading DNA
      polymerase in PCR reduced the proportion of chimerical sequences in polyploids in
      comparison to Taq polymerase.

PMID- 22479448
TI  - Sex promotes spatial and dietary segregation in a migratory shorebird during the
      non-breeding season.
AB  - Several expressions of sexual segregation have been described in animals,
      especially in those exhibiting conspicuous dimorphism. Outside the breeding
      season, segregation has been mostly attributed to size or age-mediated dominance
      or to trophic niche divergence. Regardless of the recognized implications for
      population dynamics, the ecological causes and consequences of sexual segregation
      are still poorly understood. We investigate the foraging habits of a shorebird
      showing reversed sexual dimorphism, the black-tailed godwit Limosa limosa, during
      the winter season, and found extensive segregation between sexes in spatial
      distribution, microhabitat use and dietary composition. Males and females
      exhibited high site-fidelity but differed in their distributions at estuary
      scale. Male godwits (shorter-billed) foraged more frequently in exposed mudflats
      than in patches with higher water levels, and consumed more bivalves and
      gastropods and fewer polychaetes than females. Females tended to be more
      frequently involved and to win more aggressive interactions than males. However,
      the number of aggressions recorded was low, suggesting that sexual dominance
      plays a lesser role in segregation, although its importance cannot be ruled out.
      Dimorphism in the feeding apparatus has been used to explain sex differences in
      foraging ecology and behaviour of many avian species, but few studies confirmed
      that morphologic characteristics drive individual differences within each sex. We
      found a relationship between resource use and bill size when pooling data from
      males and females. However, this relationship did not hold for either sex
      separately, suggesting that differences in foraging habits of godwits are
      primarily a function of sex, rather than bill size. Hence, the exact mechanisms
      through which this segregation operates are still unknown. The recorded
      differences in spatial distribution and resource use might expose male and female
      to distinct threats, thus affecting population dynamics through differential
      mortality. Therefore, population models and effective conservation strategies
      should increasingly take sex-specific requirements into consideration.

PMID- 22479449
TI  - Comprehensive decision tree models in bioinformatics.
AB  - PURPOSE: Classification is an important and widely used machine learning
      technique in bioinformatics. Researchers and other end-users of machine learning
      software often prefer to work with comprehensible models where knowledge
      extraction and explanation of reasoning behind the classification model are
      possible. METHODS: This paper presents an extension to an existing machine
      learning environment and a study on visual tuning of decision tree classifiers.
      The motivation for this research comes from the need to build effective and
      easily interpretable decision tree models by so called one-button data mining
      approach where no parameter tuning is needed. To avoid bias in classification, no
      classification performance measure is used during the tuning of the model that is
      constrained exclusively by the dimensions of the produced decision tree. RESULTS:
      The proposed visual tuning of decision trees was evaluated on 40 datasets
      containing classical machine learning problems and 31 datasets from the field of
      bioinformatics. Although we did not expected significant differences in
      classification performance, the results demonstrate a significant increase of
      accuracy in less complex visually tuned decision trees. In contrast to classical
      machine learning benchmarking datasets, we observe higher accuracy gains in
      bioinformatics datasets. Additionally, a user study was carried out to confirm
      the assumption that the tree tuning times are significantly lower for the
      proposed method in comparison to manual tuning of the decision tree. CONCLUSIONS:
      The empirical results demonstrate that by building simple models constrained by
      predefined visual boundaries, one not only achieves good comprehensibility, but
      also very good classification performance that does not differ from usually more
      complex models built using default settings of the classical decision tree
      algorithm. In addition, our study demonstrates the suitability of visually tuned
      decision trees for datasets with binary class attributes and a high number of
      possibly redundant attributes that are very common in bioinformatics.

PMID- 22479450
TI  - An ethanol extract of Artemisia iwayomogi activates PPARdelta leading to
      activation of fatty acid oxidation in skeletal muscle.
AB  - Although Artemisia iwayomogi (AI) has been shown to improve the lipid metabolism,
      its mode of action is poorly understood. In this study, a 95% ethanol extract of
      AI (95EEAI) was identified as a potent ligand of peroxisome proliferator
      activated receptordelta (PPARdelta) using ligand binding analysis and cell-based
      reporter assay. In cultured primary human skeletal muscle cells, treatment of
      95EEAI increased expression of two important PPARdelta-regulated genes, carnitine
      palmitoyl-transferase-1 (CPT1) and pyruvate dehydrogenase kinase isozyme 4
      (PDK4), and several genes acting in lipid efflux and energy expenditure.
      Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARdelta-dependent
      manner. High-fat diet-induced obese mice model further indicated that
      administration of 95EEAI attenuated diet-induced obesity through the activation
      of fatty acid oxidation in skeletal muscle. These results suggest that a 95%
      ethanol extract of AI may have a role as a new functional food material for the
      prevention and/or treatment of hyperlipidermia and obesity.

PMID- 22479451
TI  - The Tnt1 retrotransposon escapes silencing in tobacco, its natural host.
AB  - Retrotransposons' high capacity for mutagenesis is a threat that genomes need to
      control tightly. Transcriptional gene silencing is a general and highly effective
      control of retrotransposon expression. Yet, some retrotransposons manage to
      transpose and proliferate in plant genomes, suggesting that, as shown for plant
      viruses, retrotransposons can escape silencing. However no evidence of
      retrotransposon silencing escape has been reported. Here we analyze the silencing
      control of the tobacco Tnt1 retrotransposon and report that even though
      constructs driven by the Tnt1 promoter become silenced when stably integrated in
      tobacco, the endogenous Tnt1 elements remain active. Silencing of Tnt1-containing
      transgenes correlates with high DNA methylation and the inability to incorporate
      H2A.Z into their promoters, whereas the endogenous Tnt1 elements remain partially
      methylated at asymmetrical positions and incorporate H2A.Z upon induction. Our
      results show that the promoter of Tnt1 is a target of silencing in tobacco, but
      also that endogenous Tnt1 elements can escape this control and be expressed in
      their natural host.

PMID- 22479452
TI  - First evidence of immunomodulation in bivalves under seawater acidification and
      increased temperature.
AB  - Water acidification, temperature increases and changes in seawater salinity are
      predicted to occur in the near future. In such a global climate change (GCC)
      scenario, there is growing concern for the health status of both wild and farmed
      organisms. Bivalve molluscs, an important component of coastal marine ecosystems,
      are at risk. At the immunological level, the ability of an organism to maintain
      its immunosurveillance unaltered under adverse environmental conditions may
      enhance its survival capability. To our knowledge, only a few studies have
      investigated the effects of changing environmental parameters (as predicted in a
      GCC scenario) on the immune responses of bivalves. In the present study, the
      effects of both decreased pH values and increased temperature on the important
      immune parameters of two bivalve species were evaluated for the first time. The
      clam Chamelea gallina and the mussel Mytilus galloprovincialis, widespread along
      the coast of the Northwestern Adriatic Sea, were chosen as model organisms.
      Bivalves were exposed for 7 days to three pH values (8.1, 7.7 and 7.4) at two
      temperatures (22 and 28 degrees C). Three independent experiments were carried
      out at salinities of 28, 34 and 40 PSU. The total haemocyte count, Neutral Red
      uptake, haemolymph lysozyme activity and total protein levels were measured. The
      results obtained demonstrated that tested experimental conditions affected
      significantly most of the immune parameters measured in bivalves, even if the
      variation pattern of haemocyte responses was not always linear. Between the two
      species, C. gallina appeared more vulnerable to changing pH and temperature than
      M. galloprovincialis. Overall, this study demonstrated that climate changes can
      strongly affect haemocyte functionality in bivalves. However, further studies are
      needed to clarify better the mechanisms of action of changing environmental
      parameters, both individually and in combination, on bivalve haemocytes.

PMID- 22479453
TI  - Methamphetamine increases LPS-mediated expression of IL-8, TNF-alpha and IL-1beta
      in human macrophages through common signaling pathways.
AB  - The use of methamphetamine (MA) has increased in recent years, and is a major
      health concern throughout the world. The use of MA has been associated with an
      increased risk of acquiring HIV-1, along with an increased probability of the
      acquisition of various sexually transmitted infections. In order to determine the
      potential effects of MA exposure in the context of an infectious agent, U937
      macrophages were exposed to various combinations of MA and bacterial
      lipopolysaccharide (LPS). Treatment with MA alone caused significant increases in
      the levels of TNF-alpha, while treatment with both MA and LPS resulted in
      significant increases in TNF-alpha, IL-1beta and the chemokine IL-8. The
      increases in cytokine or chemokine levels seen when cells were treated with both
      LPS and MA were generally greater than those increases observed when cells were
      treated with only LPS. Treatment with chemical inhibitors demonstrated that the
      signal transduction pathways including NF-kB, MAPK, and PI3-Akt were involved in
      mediating the increased inflammatory response. As discussed in the paper, these
      pathways appear to be utilized by both MA and LPS, in the induction of these
      inflammatory mediators. Since these pathways are involved in the induction of
      inflammation in response to other pathogens, this suggests that MA-exacerbated
      inflammation may be a common feature of infectious disease in MA abusers.

PMID- 22479454
TI  - A reverse engineering approach to the suppression of citation biases reveals
      universal properties of citation distributions.
AB  - The large amount of information contained in bibliographic databases has recently
      boosted the use of citations, and other indicators based on citation numbers, as
      tools for the quantitative assessment of scientific research. Citations counts
      are often interpreted as proxies for the scientific influence of papers,
      journals, scholars, and institutions. However, a rigorous and scientifically
      grounded methodology for a correct use of citation counts is still missing. In
      particular, cross-disciplinary comparisons in terms of raw citation counts
      systematically favors scientific disciplines with higher citation and publication
      rates. Here we perform an exhaustive study of the citation patterns of millions
      of papers, and derive a simple transformation of citation counts able to suppress
      the disproportionate citation counts among scientific domains. We find that the
      transformation is well described by a power-law function, and that the parameter
      values of the transformation are typical features of each scientific discipline.
      Universal properties of citation patterns descend therefore from the fact that
      citation distributions for papers in a specific field are all part of the same
      family of univariate distributions.

PMID- 22479455
TI  - Expression of constitutively active CDK1 stabilizes APC-Cdh1 substrates and
      potentiates premature spindle assembly and checkpoint function in G1 cells.
AB  - Mitotic progression in eukaryotic cells depends upon the activation of cyclin
      dependent kinase 1 (CDK1), followed by its inactivation through the anaphase
      promoting complex (APC)/cyclosome-mediated degradation of M-phase cyclins.
      Previous work revealed that expression of a constitutively active CDK1 (CDK1AF)
      in HeLa cells permitted their division, but yielded G1 daughter cells that
      underwent premature S-phase and early mitotic events. While CDK1AF was found to
      impede the sustained activity of APC-Cdh1, it was unknown if this defect
      improperly stabilized mitotic substrates and contributed to the occurrence of
      these premature M phases. Here, we show that CDK1AF expression in HeLa cells
      improperly stabilized APC-Cdh1 substrates in G1-phase daughter cells, including
      mitotic kinases and the APC adaptor, Cdc20. Division of CDK1AF-expressing cells
      produced G1 daughters with an accelerated S-phase onset, interrupted by the
      formation of premature bipolar spindles capable of spindle assembly checkpoint
      function. Further characterization of these phenotypes induced by CDK1AF
      expression revealed that this early spindle formation depended upon premature
      CDK1 and Aurora B activities, and their inhibition induced rapid spindle
      disassembly. Following its normal M-phase degradation, we found that the absence
      of Wee1 in these prematurely cycling daughter cells permitted the endogenous CDK1
      to contribute to these premature mitotic events, since expression of a non
      degradable Wee1 reduced the number of cells that exhibited premature cyclin
      B1oscillations. Lastly, we discovered that Cdh1-ablated cells could not be forced
      into a premature M phase, despite cyclin B1 overexpression and proteasome
      inhibition. Together, these results demonstrate that expression of constitutively
      active CDK1AF hampers the destruction of critical APC-Cdh1 targets, and that this
      type of condition could prevent newly divided cells from properly maintaining a
      prolonged interphase state. We propose that this more subtle type of defect in
      activity of the APC-driven negative-feedback loop may have implications for
      triggering genome instability and tumorigenesis.

PMID- 22479456
TI  - miR-34a repression in proneural malignant gliomas upregulates expression of its
      target PDGFRA and promotes tumorigenesis.
AB  - Glioblastoma (GBM) and other malignant gliomas are aggressive primary neoplasms
      of the brain that exhibit notable refractivity to standard treatment regimens.
      Recent large-scale molecular profiling has revealed distinct disease subclasses
      within malignant gliomas whose defining genomic features highlight dysregulated
      molecular networks as potential targets for therapeutic development. The
      "proneural" designation represents the largest and most heterogeneous of these
      subclasses, and includes both a large fraction of GBMs along with most of their
      lower-grade astrocytic and oligodendroglial counterparts. The pathogenesis of
      proneural gliomas has been repeatedly associated with dysregulated PDGF
      signaling. Nevertheless, genomic amplification or activating mutations involving
      the PDGF receptor (PDGFRA) characterize only a subset of proneural GBMs, while
      the mechanisms driving dysregulated PDGF signaling and downstream oncogenic
      networks in remaining tumors are unclear. MicroRNAs (miRNAs) are a class of
      small, noncoding RNAs that regulate gene expression by binding loosely
      complimentary sequences in target mRNAs. The role of miRNA biology in numerous
      cancer variants is well established. In an analysis of miRNA involvement in the
      phenotypic expression and regulation of oncogenic PDGF signaling, we found that
      miR-34a is downregulated by PDGF pathway activation in vitro. Similarly, analysis
      of data from the Cancer Genome Atlas (TCGA) revealed that miR-34a expression is
      significantly lower in proneural gliomas compared to other tumor subtypes. Using
      primary GBM cells maintained under neurosphere conditions, we then demonstrated
      that miR-34a specifically affects growth of proneural glioma cells in vitro and
      in vivo. Further bioinformatic analysis identified PDGFRA as a direct target of
      miR-34a and this interaction was experimentally validated. Finally, we found that
      PDGF-driven miR-34a repression is unlikely to operate solely through a p53
      dependent mechanism. Taken together, our data support the existence of reciprocal
      negative feedback regulation involving miR-34 and PDGFRA expression in proneural
      gliomas and, as such, identify a subtype specific therapeutic potential for miR
      34a.

PMID- 22479457
TI  - Subcellular location, phosphorylation and assembly into the motor complex of
      GAP45 during Plasmodium falciparum schizont development.
AB  - An actomyosin motor complex assembled below the parasite's plasma membrane drives
      erythrocyte invasion by Plasmodium falciparum merozoites. The complex is
      comprised of several proteins including myosin (MyoA), myosin tail domain
      interacting protein (MTIP) and glideosome associated proteins (GAP) 45 and 50,
      and is anchored on the inner membrane complex (IMC), which underlies the
      plasmalemma. A ternary complex of MyoA, MTIP and GAP45 is formed that then
      associates with GAP50. We show that full length GAP45 labelled internally with
      GFP is assembled into the motor complex and transported to the developing IMC in
      early schizogony, where it accumulates during intracellular development until
      merozoite release. We show that GAP45 is phosphorylated by calcium dependent
      protein kinase 1 (CDPK1), and identify the modified serine residues. Replacing
      these serine residues with alanine or aspartate has no apparent effect on GAP45
      assembly into the motor protein complex or its subcellular location in the
      parasite. The early assembly of the motor complex suggests that it has functions
      in addition to its role in erythrocyte invasion.

PMID- 22479458
TI  - Sex matters during adolescence: testosterone-related cortical thickness
      maturation differs between boys and girls.
AB  - Age-related changes in cortical thickness have been observed during adolescence,
      including thinning in frontal and parietal cortices, and thickening in the
      lateral temporal lobes. Studies have shown sex differences in hormone-related
      brain maturation when boys and girls are age-matched, however, because girls
      mature 1-2 years earlier than boys, these sex differences could be confounded by
      pubertal maturation. To address puberty effects directly, this study assessed sex
      differences in testosterone-related cortical maturation by studying 85 boys and
      girls in a narrow age range and matched on sexual maturity. We expected that
      testosterone-by-sex interactions on cortical thickness would be observed in brain
      regions known from the animal literature to be high in androgen receptors. We
      found sex differences in associations between circulating testosterone and
      thickness in left inferior parietal lobule, middle temporal gyrus, calcarine
      sulcus, and right lingual gyrus, all regions known to be high in androgen
      receptors. Visual areas increased with testosterone in boys, but decreased in
      girls. All other regions were more impacted by testosterone levels in girls than
      boys. The regional pattern of sex-by-testosterone interactions may have
      implications for understanding sex differences in behavior and adolescent-onset
      neuropsychiatric disorders.

PMID- 22479459
TI  - Fast and robust characterization of time-heterogeneous sequence evolutionary
      processes using substitution mapping.
AB  - Genes and genomes do not evolve similarly in all branches of the tree of life.
      Detecting and characterizing the heterogeneity in time, and between lineages, of
      the nucleotide (or amino acid) substitution process is an important goal of
      current molecular evolutionary research. This task is typically achieved through
      the use of non-homogeneous models of sequence evolution, which being highly
      parametrized and computationally-demanding are not appropriate for large-scale
      analyses. Here we investigate an alternative methodological option based on
      probabilistic substitution mapping. The idea is to first reconstruct the
      substitutional history of each site of an alignment under a homogeneous model of
      sequence evolution, then to characterize variations in the substitution process
      across lineages based on substitution counts. Using simulated and published
      datasets, we demonstrate that probabilistic substitution mapping is robust in
      that it typically provides accurate reconstruction of sequence ancestry even when
      the true process is heterogeneous, but a homogeneous model is adopted.
      Consequently, we show that the new approach is essentially as efficient as and
      extremely faster than (up to 25 000 times) existing methods, thus paving the way
      for a systematic survey of substitution process heterogeneity across genes and
      lineages.

PMID- 22479461
TI  - Coupling and elastic loading affect the active response by the inner ear hair
      cell bundles.
AB  - Active hair bundle motility has been proposed to underlie the amplification
      mechanism in the auditory endorgans of non-mammals and in the vestibular systems
      of all vertebrates, and to constitute a crucial component of cochlear
      amplification in mammals. We used semi-intact in vitro preparations of the
      bullfrog sacculus to study the effects of elastic mechanical loading on both
      natively coupled and freely oscillating hair bundles. For the latter, we attached
      glass fibers of different stiffness to the stereocilia and observed the induced
      changes in the spontaneous bundle movement. When driven with sinusoidal
      deflections, hair bundles displayed phase-locked response indicative of an Arnold
      Tongue, with the frequency selectivity highest at low amplitudes and decreasing
      under stronger stimulation. A striking broadening of the mode-locked response was
      seen with increasing stiffness of the load, until approximate impedance matching,
      where the phase-locked response remained flat over the physiological range of
      frequencies. When the otolithic membrane was left intact atop the preparation,
      the natural loading of the bundles likewise decreased their frequency selectivity
      with respect to that observed in freely oscillating bundles. To probe for
      signatures of the active process under natural loading and coupling conditions,
      we applied transient mechanical stimuli to the otolithic membrane. Following the
      pulses, the underlying bundles displayed active movement in the opposite
      direction, analogous to the twitches observed in individual cells. Tracking
      features in the otolithic membrane indicated that it moved in phase with the
      bundles. Hence, synchronous active motility evoked in the system of coupled hair
      bundles by external input is sufficient to displace large overlying structures.

PMID- 22479460
TI  - MicroRNA-34c enhances murine male germ cell apoptosis through targeting ATF1.
AB  - BACKGROUND: MicroRNAs (miRNAs) play vital regulatory roles in many cellular
      processes. The expression of miRNA (miR)-34c is highly enriched in adult mouse
      testis, but its roles and underlying mechanisms of action are not well
      understood. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we show that
      miR-34c is detected in mouse pachytene spermatocytes and continues to be highly
      expressed in spermatids. To explore the specific functions of miR-34c, we have
      established an in vivo model by transfecting miR-34c inhibitors into primary
      spermatocytes to study the loss-of-function of miR-34c. The results show that
      silencing of miR-34c significantly increases the Bcl-2/Bax ratio and prevents
      germ cell from apoptosis induced by deprivation of testosterone. Moreover,
      ectopic expression of the miR-34c in GC-2 cell trigger the cell apoptosis with a
      decreased Bcl-2/Bax ratio and miR-34c inhibition lead to a low spontaneous
      apoptotic ratio and an increased Bcl-2/Bax ratio. Furthermore, ectopic expression
      of miR-34c reduces ATF1 protein expression without affecting ATF1 mRNA level via
      directly binding to ATF1's 3'UTR, indicating that ATF1 is one of miR-34c's target
      genes. Meanwhile, the knockdown of ATF1 significantly decreases the Bcl-2/Bax
      ratio and triggers GC-2 cell apoptosis. Inhibition of miR-34c does not decrease
      the GC-2 cell apoptosis ratio in ATF1 knockdown cells. CONCLUSIONS/SIGNIFICANCE:
      Our study shows for the first time that miR-34c functions, at least partially, by
      targeting the ATF1 gene in germ cell apoptosis, providing a novel mechanism with
      involvement of miRNA in the regulation of germ cell apoptosis.

PMID- 22479462
TI  - Cross-species analyses identify the BNIP-2 and Cdc42GAP homology (BCH) domain as
      a distinct functional subclass of the CRAL_TRIO/Sec14 superfamily.
AB  - The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily,
      binds to a diverse set of small lipophilic ligands. Similar domains are found in
      a range of different proteins including neurofibromatosis type-1, a Ras GTPase
      activating Protein (RasGAP) and Rho guanine nucleotide exchange factors
      (RhoGEFs). Proteins containing this structural protein domain exhibit a low
      sequence similarity and ligand specificity while maintaining an overall
      characteristic three-dimensional structure. We have previously demonstrated that
      the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low
      sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold
      that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling
      processes. In this work, we investigate 175 BCH domain-containing proteins from a
      wide range of different organisms. A phylogenetic analysis with ~100 CRAL_TRIO
      and similar domains from eight representative species indicates a clear
      distinction of BCH-containing proteins as a novel subclass within the
      CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence
      motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs ('h' is large and hydrophobic residue and
      's' is small and weekly polar residue) and can be further subdivided into three
      unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains.
      A previously unknown group of genes encoding 'BCH-only' domains is also
      identified in plants and arthropod species. Based on an analysis of their gene
      structure and their protein domain context we hypothesize that BCH domain
      containing genes evolved through gene duplication, intron insertions and domain
      swapping events. Furthermore, we explore the point of divergence between BCH and
      CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and
      GEFs and lipid ligands. Our study suggests a need for a more extensive analysis
      of previously uncharacterized BCH, 'BCH-like' and CRAL_TRIO-containing proteins
      and their significance in regulating signaling events involving small GTPases.

PMID- 22479463
TI  - Efficient and specific analysis of red blood cell glycerophospholipid fatty acid
      composition.
AB  - BACKGROUND: Red blood cell (RBC) n-3 fatty acid status is related to various
      health outcomes. Accepted biological markers for the fatty acid status
      determination are RBC phospholipids, phosphatidylcholine, and
      phosphatidyletholamine. The analysis of these lipid fractions is demanding and
      time consuming and total phospholipid n-3 fatty acid levels might be affected by
      changes of sphingomyelin contents in the RBC membrane during n-3 supplementation.
      AIM: We developed a method for the specific analysis of RBC glycerophospholipids.
      The application of the new method in a DHA supplementation trial and the
      comparison to established markers will determine the relevance of RBC GPL as a
      valid fatty acid status marker in humans. METHODS: Methyl esters of
      glycerophospholipid fatty acids are selectively generated by a two step procedure
      involving methanolic protein precipitation and base-catalysed methyl ester
      synthesis. RBC GPL solubilisation is facilitated by ultrasound treatment. Fatty
      acid status in RBC glycerophospholipids and other established markers were
      evaluated in thirteen subjects participating in a 30 days supplementation trial
      (510 mg DHA/d). OUTCOME: The intra-assay CV for GPL fatty acids ranged from 1.0
      to 10.5% and the inter-assay CV from 1.3 to 10.9%. Docosahexaenoic acid
      supplementation significantly increased the docosahexaenoic acid contents in all
      analysed lipid fractions. High correlations were observed for most of the mono-
      and polyunsaturated fatty acids, and for the omega-3 index (r = 0.924) between
      RBC phospholipids and glycerophospholipids. The analysis of RBC
      glycerophospholipid fatty acids yields faster, easier and less costly results
      equivalent to the conventional analysis of RBC total phospholipids.

PMID- 22479464
TI  - High resolution intravital imaging of subcellular structures of mouse abdominal
      organs using a microstage device.
AB  - Intravital imaging of brain and bone marrow cells in the skull with subcellular
      resolution has revolutionized neurobiology, immunology and hematology. However,
      the application of this powerful technology in studies of abdominal organs has
      long been impeded by organ motion caused by breathing and heartbeat. Here we
      describe for the first time a simple device designated 'microstage' that
      effectively reduces organ motions without causing tissue lesions. Combining this
      microstage device with an upright intravital laser scanning microscope equipped
      with a unique stick-type objective lens, the system enables subcellular-level
      imaging of abdominal organs in live mice. We demonstrate that this technique
      allows for the quantitative analysis of subcellular structures and gene
      expressions in cells, the tracking of intracellular processes in real-time as
      well as three-dimensional image construction in the pancreas and liver of the
      live mouse. As the aforementioned analyses based on subcellular imaging could be
      extended to other intraperitoneal organs, the technique should offer great
      potential for investigation of physiological and disease-specific events of
      abdominal organs. The microstage approach adds an exciting new technique to the
      in vivo imaging toolbox.

PMID- 22479465
TI  - Population genetics of two asexually and sexually reproducing psocids species
      inferred by the analysis of mitochondrial and nuclear DNA sequences.
AB  - BACKGROUND: The psocids Liposcelis bostrychophila and L. entomophila (Psocoptera:
      Liposcelididae) are found throughout the world and are often associated with
      humans, food stores and habitations. These insects have developed high levels of
      resistance to various insecticides in grain storage systems. However, the
      population genetic structure and gene flow of psocids has not been well
      categorized, which is helpful to plan appropriate strategies for the control of
      these pests. METHODOLOGY/PRINCIPAL FINDINGS: The two species were sampled from 15
      localities in China and analyzed for polymorphisms at the mitochondrial DNA
      (Cytb) and ITS (ITS1-5.8S-ITS2) regions. In total, 177 individual L.
      bostrychophila and 272 individual L. entomophila were analysed. Both Cytb and ITS
      sequences showed high genetic diversity for the two species with haplotype
      diversities ranged from 0.154 +/- 0.126 to 1.000 +/- 0.045, and significant
      population differentiation (mean F(ST) = 0.358 for L. bostrychophila; mean F(ST)
      = 0.336 for L. entomophila) was also detected among populations investigated. A
      Mantel test indicated that for both species there was no evidence for isolation
      by-distance (IBD). The neutrality test and mismatch distribution statistics
      revealed that the two species might have undergone population expansions in the
      past. CONCLUSION: Both L. bostrychophila and L. entomophila displayed high
      genetic diversity and widespread population genetic differentiation within and
      between populations. The significant population differentiation detected for both
      psocids may be mainly due to other factors, such as genetic drift, inbreeding or
      control practices, and less by geographic distance since an IBD effect was not
      found.

PMID- 22479466
TI  - GPS-MBA: computational analysis of MHC class II epitopes in type 1 diabetes.
AB  - As a severe chronic metabolic disease and autoimmune disorder, type 1 diabetes
      (T1D) affects millions of people world-wide. Recent advances in antigen-based
      immunotherapy have provided a great opportunity for further treating T1D with a
      high degree of selectivity. It is reported that MHC class II I-A(g7) in the non
      obese diabetic (NOD) mouse and human HLA-DQ8 are strongly linked to
      susceptibility to T1D. Thus, the identification of new I-A(g7) and HLA-DQ8
      epitopes would be of great help to further experimental and biomedical
      manipulation efforts. In this study, a novel GPS-MBA (MHC Binding Analyzer)
      software package was developed for the prediction of I-A(g7) and HLA-DQ8
      epitopes. Using experimentally identified epitopes as the training data sets, a
      previously developed GPS (Group-based Prediction System) algorithm was adopted
      and improved. By extensive evaluation and comparison, the GPS-MBA performance was
      found to be much better than other tools of this type. With this powerful tool,
      we predicted a number of potentially new I-A(g7) and HLA-DQ8 epitopes.
      Furthermore, we designed a T1D epitope database (TEDB) for all of the
      experimentally identified and predicted T1D-associated epitopes. Taken together,
      this computational prediction result and analysis provides a starting point for
      further experimental considerations, and GPS-MBA is demonstrated to be a useful
      tool for generating starting information for experimentalists. The GPS-MBA is
      freely accessible for academic researchers at: http://mba.biocuckoo.org.

PMID- 22479467
TI  - Identification of novel Mt-Guab2 inhibitor series active against M. tuberculosis.
AB  - Tuberculosis (TB) remains a leading cause of mortality worldwide. With the
      emergence of multidrug resistant TB, extensively drug resistant TB and HIV
      associated TB it is imperative that new drug targets be identified. The potential
      of Mycobacterium tuberculosis inosine monophosphate dehydrogenase (IMPDH) as a
      novel drug target was explored in the present study. IMPDH exclusively catalyzes
      the conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP)
      in the presence of the cofactor nicotinamide adenine dinucleotide (NAD(+)).
      Although the enzyme is a dehydrogenase, the enzyme does not catalyze the reverse
      reaction i.e. the conversion of XMP to IMP. Unlike other bacteria, M.
      tuberculosis harbors three IMPDH-like genes, designated as Mt-guaB1, Mt-guaB2 and
      Mt-guaB3 respectively. Of the three putative IMPDH's, we previously confirmed
      that Mt-GuaB2 was the only functional ortholog by characterizing the enzyme
      kinetically. Using an in silico approach based on designed scaffolds, a series of
      novel classes of inhibitors was identified. The inhibitors possess good activity
      against M. tuberculosis with MIC values in the range of 0.4 to 11.4 ug mL(-1).
      Among the identified ligands, two inhibitors have nanomolar K(i)s against the Mt
      GuaB2 enzyme.

PMID- 22479468
TI  - Functional identification and characterization of the Brassica napus
      transcription factor gene BnAP2, the ortholog of Arabidopsis thaliana APETALA2.
AB  - BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus
      cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a
      transcription factor comprising of 432 amino acid residues. Results from
      complementary experiment indicated that BnAP2 was completely capable of restoring
      the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and
      expression data, the complementation data suggested that BnAP2 encodes the
      ortholog of AtAP2. To address the transcriptional activation of BnAP2, we
      performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA
      binding domain strongly activated transcription in yeast, and the transactivating
      activity of BnAP2 was localized to the N-terminal 100 amino acids. To further
      study the function of BnAP2 involved in the phenotype of B. napus, we used a
      transgenic approach that involved targeted RNA interference (RNAi) repression
      induced by ihp-RNA. Floral various phenotype defectives and reduced female
      fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of
      BnAP2 gene also resulted in delayed sepal abscission and senescence with the
      ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed
      defects in shape, structure and development and larger size. Strong BnAP2-RNAi
      and wild-type seeds initially did not display a significant difference in
      morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than
      that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were
      essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and
      developing and gradually withered.

PMID- 22479469
TI  - Pharmacokinetic modeling of an induction regimen for in vivo combined testing of
      novel drugs against pediatric acute lymphoblastic leukemia xenografts.
AB  - Current regimens for induction therapy of pediatric acute lymphoblastic leukemia
      (ALL), or for re-induction post relapse, use a combination of vincristine (VCR),
      a glucocorticoid, and L-asparaginase (ASP) with or without an anthracycline. With
      cure rates now approximately 80%, robust pre-clinical models are necessary to
      prioritize active new drugs for clinical trials in relapsed/refractory patients,
      and the ability of these models to predict synergy/antagonism with established
      therapy is an essential attribute. In this study, we report optimization of an
      induction-type regimen by combining VCR, dexamethasone (DEX) and ASP (VXL)
      against ALL xenograft models established from patient biopsies in immune
      deficient mice. We demonstrate that the VXL combination was synergistic in vitro
      against leukemia cell lines as well as in vivo against ALL xenografts. In vivo,
      VXL treatment caused delays in progression of individual xenografts ranging from
      22 to >146 days. The median progression delay of xenografts derived from long
      term surviving patients was 2-fold greater than that of xenografts derived from
      patients who died of their disease. Pharmacokinetic analysis revealed that
      systemic DEX exposure in mice increased 2-fold when administered in combination
      with VCR and ASP, consistent with clinical findings, which may contribute to the
      observed synergy between the 3 drugs. Finally, as proof-of-principle we tested
      the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w
      inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo
      platform to prioritize new drugs for clinical trials in children with
      relapsed/refractory ALL.

PMID- 22479470
TI  - A rapid and highly sensitive method of non radioactive colorimetric in situ
      hybridization for the detection of mRNA on tissue sections.
AB  - BACKGROUND: Non Radioactive colorimetric In Situ Hybridization (NoRISH) with
      hapten labeled probes has been widely used for the study of gene expression in
      development, homeostasis and disease. However, improvement in the sensitivity of
      the method is still needed to allow for the analysis of genes expressed at low
      levels. METHODOLOGY/PRINCIPAL FINDINGS: A stable, non-toxic, zinc-based fixative
      was tested in NoRISH experiments on sections of mouse embryos using four probes
      (Lhx6, Lhx7, ncapg and ret) that have different spatial patterns and expression
      levels. We showed that Z7 can successfully replace paraformaldehyde used so far
      for tissue fixation in NoRISH; the morphology of the cryosections of Z7-fixed
      tissues was excellent, and the fixation time required for tissues sized 1 cm was
      1 hr instead of 24 hr for paraformaldehyde. The hybridization signal on the
      sections of the Z7-treated embryos always appeared earlier than that of the PFA
      fixed embryos. In addition, a 50-60% shorter detection time was observed in
      specimen of Z7-treated embryos, reducing significantly the time required to
      complete the method. Finally and most importantly, the strength of the
      hybridization signal on the sections of the Z7-treated embryos always compared
      favorably to that of the sections of PFA-fixed embryos; these data demonstrate a
      significant improvement of the sensitivity the method that allows for the
      analysis of mRNAs that are barely or not detected by the standard colorimetric
      NoRISH method. CONCLUSIONS/SIGNIFICANCE: Our NoRISH method provides excellent
      preservation of tissue morphology, is rapid, highly sensitive, and especially
      suitable to implement in the study of genes expressed at low levels and/or in
      sparse cells within a structure.

PMID- 22479472
TI  - Genetic diversity of Mycobacterium tuberculosis isolates from Tibetans in Tibet,
      China.
AB  - BACKGROUND: Tuberculosis (TB) is a serious health problem in Tibet where Tibetans
      are the major ethnic group. Although genotyping of Mycobacterium tuberculosis (M.
      tuberculosis) isolates is a valuable tool for TB control, our knowledge of
      population structure of M. tuberculosis circulating in Tibet is limited.
      METHODOLOGY/PRINCIPAL FINDINGS: In our study, a total of 576 M. tuberculosis
      isolates from Tibetans in Tibet, China, were analyzed via spoligotyping and 24
      locus MIRU-VNTR. The Beijing genotype was the most prevalent family (90.63%, n =
      522). Shared-type (ST) 1 was the most dominant genotype (88.89%, n = 512). We
      found that there was no association between the Beijing genotype and sex, age and
      treatment status. In this sample collection, 7 of the 24 MIRU-VNTR loci were
      highly or moderately discriminative according to their Hunter-Gaston
      discriminatory index. An informative set of 12 loci had similar discriminatory
      power with 24 loci set. CONCLUSIONS/SIGNIFICANCE: The population structure of M.
      tuberculosis isolates in Tibetans is homogeneous and dominated by Beijing
      genotype. The analysis of 24-locus MIRU-VNTR data might be useful to select
      appropriate VNTR loci for the genotyping of M. tuberculosis.

PMID- 22479471
TI  - Comparative omics-driven genome annotation refinement: application across
      Yersiniae.
AB  - Genome sequencing continues to be a rapidly evolving technology, yet most
      downstream aspects of genome annotation pipelines remain relatively stable or are
      even being abandoned. The annotation process is now performed almost exclusively
      in an automated fashion to balance the large number of sequences generated. One
      possible way of reducing errors inherent to automated computational annotations
      is to apply data from omics measurements (i.e. transcriptional and proteomic) to
      the un-annotated genome with a proteogenomic-based approach. Here, the concept of
      annotation refinement has been extended to include a comparative assessment of
      genomes across closely related species. Transcriptomic and proteomic data derived
      from highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis Pestoides F,
      and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive
      comparative omic-based annotation methodology. Peptide and oligo measurements
      experimentally validated the expression of nearly 40% of each strain's predicted
      proteome and revealed the identification of 28 novel and 68 incorrect (i.e.,
      observed frameshifts, extended start sites, and translated pseudogenes) protein
      coding sequences within the three current genome annotations. Gene loss is
      presumed to play a major role in Y. pestis acquiring its niche as a virulent
      pathogen, thus the discovery of many translated pseudogenes, including the
      insertion-ablated argD, underscores a need for functional analyses to investigate
      hypotheses related to divergence. Refinements included the discovery of a
      seemingly essential ribosomal protein, several virulence-associated factors, a
      transcriptional regulator, and many hypothetical proteins that were missed during
      annotation.

PMID- 22479473
TI  - Perceived surface slant is systematically biased in the actively-generated optic
      flow.
AB  - Humans make systematic errors in the 3D interpretation of the optic flow in both
      passive and active vision. These systematic distortions can be predicted by a
      biologically-inspired model which disregards self-motion information resulting
      from head movements (Caudek, Fantoni, & Domini 2011). Here, we tested two
      predictions of this model: (1) A plane that is stationary in an earth-fixed
      reference frame will be perceived as changing its slant if the movement of the
      observer's head causes a variation of the optic flow; (2) a surface that rotates
      in an earth-fixed reference frame will be perceived to be stationary, if the
      surface rotation is appropriately yoked to the head movement so as to generate a
      variation of the surface slant but not of the optic flow. Both predictions were
      corroborated by two experiments in which observers judged the perceived slant of
      a random-dot planar surface during egomotion. We found qualitatively similar
      biases for monocular and binocular viewing of the simulated surfaces, although,
      in principle, the simultaneous presence of disparity and motion cues allows for a
      veridical recovery of surface slant.

PMID- 22479474
TI  - Modeling the emergence of circadian rhythms in a clock neuron network.
AB  - Circadian rhythms in pacemaker cells persist for weeks in constant darkness,
      while in other types of cells the molecular oscillations that underlie circadian
      rhythms damp rapidly under the same conditions. Although much progress has been
      made in understanding the biochemical and cellular basis of circadian rhythms,
      the mechanisms leading to damped or self-sustained oscillations remain largely
      unknown. There exist many mathematical models that reproduce the circadian
      rhythms in the case of a single cell of the Drosophila fly. However, not much is
      known about the mechanisms leading to coherent circadian oscillation in clock
      neuron networks. In this work we have implemented a model for a network of
      interacting clock neurons to describe the emergence (or damping) of circadian
      rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an
      array of pacemakers that interact through the modulation of some parameters by a
      network feedback. The individual pacemakers are described by a well-known
      biochemical model for circadian oscillation, to which we have added degradation
      of PER protein by light and multiplicative noise. The network feedback is the PER
      protein level averaged over the whole network. In particular, we have
      investigated the effect of modulation of the parameters associated with (i) the
      control of net entrance of PER into the nucleus and (ii) the non-photic
      degradation of PER. Our results indicate that the modulation of PER entrance into
      the nucleus allows the synchronization of clock neurons, leading to coherent
      circadian oscillations under constant dark condition. On the other hand, the
      modulation of non-photic degradation cannot reset the phases of individual clocks
      subjected to intrinsic biochemical noise.

PMID- 22479475
TI  - Chemical clearing and dehydration of GFP expressing mouse brains.
AB  - Generally, chemical tissue clearing is performed by a solution consisting of two
      parts benzyl benzoate and one part benzyl alcohol. However, prolonged exposure to
      this mixture markedly reduces the fluorescence of GFP expressing specimens, so
      that one has to compromise between clearing quality and fluorescence
      preservation. This can be a severe drawback when working with specimens
      exhibiting low GFP expression rates. Thus, we screened for a substitute and found
      that dibenzyl ether (phenylmethoxymethylbenzene, CAS 103-50-4) can be applied as
      a more GFP-friendly clearing medium. Clearing with dibenzyl ether provides
      improved tissue transparency and strikingly improved fluorescence intensity in
      GFP expressing mouse brains and other samples as mouse spinal cords, or embryos.
      Chemical clearing, staining, and embedding of biological samples mostly requires
      careful foregoing tissue dehydration. The commonly applied tissue dehydration
      medium is ethanol, which also can markedly impair GFP fluorescence. Screening for
      a substitute also for ethanol we found that tetrahydrofuran (CAS 109-99-9) is a
      more GFP-friendly dehydration medium than ethanol, providing better tissue
      transparency obtained by successive clearing. Combined, tetrahydrofuran and
      dibenzyl ether allow dehydration and chemical clearing of even delicate samples
      for UM, confocal microscopy, and other microscopy techniques.

PMID- 22479476
TI  - Apolipoprotein A-I attenuates palmitate-mediated NF-kappaB activation by reducing
      Toll-like receptor-4 recruitment into lipid rafts.
AB  - While high-density lipoprotein (HDL) is known to protect against a wide range of
      inflammatory stimuli, its anti-inflammatory mechanisms are not well understood.
      Furthermore, HDL's protective effects against saturated dietary fats have not
      been previously described. In this study, we used endothelial cells to
      demonstrate that while palmitic acid activates NF-kappaB signaling,
      apolipoprotein A-I, (apoA-I), the major protein component of HDL, attenuates
      palmitate-induced NF-kappaB activation. Further, vascular NF-kappaB signaling (IL
      6, MCP-1, TNF-alpha) and macrophage markers (CD68, CD11c) induced by 24 weeks of
      a diabetogenic diet containing cholesterol (DDC) is reduced in human apoA-I
      overexpressing transgenic C57BL/6 mice compared to age-matched WT controls.
      Moreover, WT mice on DDC compared to a chow diet display increased gene
      expression of lipid raft markers such as Caveolin-1 and Flotillin-1, and
      inflammatory Toll-like receptors (TLRs) (TLR2, TLR4) in the vasculature. However
      apoA-I transgenic mice on DDC show markedly reduced expression of these genes.
      Finally, we show that in endothelial cells TLR4 is recruited into lipid rafts in
      response to palmitate, and that apoA-I prevents palmitate-induced TLR4
      trafficking into lipid rafts, thereby blocking NF-kappaB activation. Thus, apoA-I
      overexpression might be a useful therapeutic tool against vascular inflammation.

PMID- 22479477
TI  - Variation of basal EROD activities in ten passerine bird species--relationships
      with diet and migration status.
AB  - Inter-specific differences in animal defence mechanisms against toxic substances
      are currently poorly understood. The ethoxyresorufin-O-deethylase (EROD) enzyme
      plays an important role in defence against toxic chemicals in a wide variety of
      animals, and it is an important biomarker for environmental contamination. We
      compared basal hepatic EROD activity levels among ten passerine species to see if
      there is inter-specific variation in enzyme activity, especially in relation to
      their diet and migration status. Migratory insectivores showed higher EROD
      activity compared to granivores. We hypothesize that the variable invertebrate
      diet of migratory insectivores contains a wider range of natural toxins than the
      narrower diet of granivores. This may have affected the evolution of mixed
      function oxidases (MFO) system and enzyme activities. We further tested whether
      metabolic rates or relative liver size were associated with the variation in
      detoxification capacity. We found no association between EROD activity and
      relative (per mass unit) basal metabolic rate (BMR). Instead, EROD activity and
      relative liver mass (% of body mass) correlated positively, suggesting that a
      proportionally large liver also functions efficiently. Our results suggest that
      granivores and non-migratory birds may be more vulnerable to environmental
      contaminants than insectivores and migratory birds. The diet and migration
      status, however, are phylogenetically strongly connected to each other, and their
      roles cannot be fully separated in our analysis with only ten passerine species.

PMID- 22479478
TI  - The glycosylation pattern of common allergens: the recognition and uptake of Der
      p 1 by epithelial and dendritic cells is carbohydrate dependent.
AB  - Allergens are initiators of both innate and adaptive immune responses. They are
      recognised at the site of entry by epithelial and dendritic cells (DCs), both of
      which activate innate inflammatory circuits that can collectively induce Th2
      immune responses. In an attempt to have a better understanding of the role of
      carbohydrates in the recognition and uptake of allergens by the innate immune
      system, we defined common glycosylation patterns in major allergens. This was
      done using labelled lectins and showed that allergens like Der p 1
      (Dermatophagoides pteronyssinus group 1), Fel d 1 (Felis domisticus), Ara h 1
      (Arachis hypogaea), Der p 2 (Dermatophagoides pteronyssinus group 2), Bla g 2
      (Blattella germanica) and Can f 1 (Canis familiaris) are glycosylated and that
      the main dominant sugars on these allergens are 1-2, 1-3 and 1-6 mannose. These
      observations are in line with recent reports implicating the mannose receptor
      (MR) in allergen recognition and uptake by DCs and suggesting a major link
      between glycosylation and allergen recognition. We then looked at TSLP (Thymic
      Stromal Lymphopoietin) cytokine secretion by lung epithelia upon encountering
      natural Der p 1 allergen. TSLP is suggested to drive DC maturation in support of
      allergic hypersensitivity reactions. Our data showed an increase in TSLP
      secretion by lung epithelia upon stimulation with natural Der p 1 which was
      carbohydrate dependent. The deglycosylated preparation of Der p 1 exhibited
      minimal uptake by DCs compared to the natural and hyperglycosylated recombinant
      counterparts, with the latter being taken up more readily than the other
      preparations. Collectively, our data indicate that carbohydrate moieties on
      allergens play a vital role in their recognition by innate immune cells,
      implicating them in downstream deleterious Th2 cell activation and IgE
      production.

PMID- 22479479
TI  - TAP1-deficiency does not alter atherosclerosis development in Apoe-/- mice.
AB  - Antigen presenting cells (APC) have the ability to present both extra-cellular
      and intra-cellular antigens via MHC class I molecules to CD8(+) T cells. The
      cross presentation of extra-cellular antigens is reduced in mice with deficient
      Antigen Peptide Transporter 1 (TAP1)-dependent MHC class I antigen presentation,
      and these mice are characterized by a diminished CD8(+) T cell population. We
      have recently reported an increased activation of CD8(+) T cells in
      hypercholesterolemic Apoe(-/-) mice. Therefore, this study included TAP1
      deficient Apoe(-/-) mice (Apoe(-/-)Tap1(-/-)) to test the atherogenicity of
      CD8(+) T cells and TAP1-dependent cross presentation in a hypercholesterolemic
      environment. As expected the CD8(+) T cell numbers were low in Apoe(-/-)Tap1(-/-)
      mice in comparison to Apoe(-/-) mice, constituting ~1% of the lymphocyte
      population. In spite of this there were no differences in the extent of
      atherosclerosis as assessed by en face Oil Red O staining of the aorta and cross
      sections of the aortic root between Apoe(-/-)Tap1(-/-) and Apoe(-/-) mice.
      Moreover, no differences were detected in lesion infiltration of macrophages or
      CD3(+) T cells in Apoe(-/-)Tap1(-/-) compared to Apoe(-/-) mice. The CD3(+)CD4(+)
      T cell fraction was increased in Apoe(-/-)Tap1(-/-) mice, suggesting a
      compensation for the decreased CD8(+) T cell population. Interestingly, the
      fraction of CD8(+) effector memory T cells was increased but this appeared to
      have little impact on the atherosclerosis development.In conclusion, Apoe(-/
      )Tap1(-/-) mice develop atherosclerosis equal to Apoe(-/-) mice, indicating a
      minor role for CD8(+) T cells and TAP1-dependent antigen presentation in the
      disease process.

PMID- 22479480
TI  - Expression analysis of LEDGF/p75, APOBEC3G, TRIM5alpha, and tetherin in a
      Senegalese cohort of HIV-1-exposed seronegative individuals.
AB  - BACKGROUND: HIV-1 replication depends on a delicate balance between cellular co
      factors and antiviral restriction factors. Lens epithelium-derived growth factor
      (LEDGF/p75) benefits HIV, whereas apolipoprotein B mRNA-editing catalytic
      polypeptide-like 3G (APOBEC3G), tripartite motif 5alpha (TRIM5alpha), and
      tetherin exert anti-HIV activity. Expression levels of these proteins possibly
      contribute to HIV-1 resistance in HIV-1-exposed populations.
      METHODOLOGY/PRINCIPAL FINDINGS: We used real-time PCR and flow cytometry to study
      mRNA and protein levels respectively in PBMC and PBMC subsets. We observed
      significantly reduced LEDGF/p75 protein levels in CD4+ lymphocytes of HIV-1
      exposed seronegative subjects relative to healthy controls, whereas we found no
      differences in APOBEC3G, TRIM5alpha, or tetherin expression. Untreated HIV-1
      infected patients generally expressed higher mRNA and protein levels than healthy
      controls. Increased tetherin levels, in particular, correlated with markers of
      disease progression: directly with the viral load and T cell activation and
      inversely with the CD4 count. CONCLUSIONS/SIGNIFICANCE: Our data suggest that
      reduced LEDGF/p75 levels may play a role in resistance to HIV-1 infection, while
      increased tetherin levels could be a marker of advanced HIV disease. Host factors
      that influence HIV-1 infection and disease could be important targets for new
      antiviral therapies.

PMID- 22479481
TI  - Developmental reaction norms for water stressed seedlings of succulent cacti.
AB  - Succulent cacti are remarkable plants with capabilities to withstand long periods
      of drought. However, their adult success is contingent on the early seedling
      stages, when plants are highly susceptible to the environment. To better
      understand their early coping strategies in a challenging environment, two
      developmental aspects (anatomy and morphology) in Polaskia chichipe and
      Echinocactus platyacanthus were studied in the context of developmental reaction
      norms under drought conditions. The morphology was evaluated using landmark based
      morphometrics and Principal Component Analysis, which gave three main trends of
      the variation in each species. The anatomy was quantified as number and area of
      xylem vessels. The quantitative relationship between morphology and anatomy in
      early stages of development, as a response to drought was revealed in these two
      species. Qualitatively, collapsible cells and collapsible parenchyma tissue were
      observed in seedlings of both species, more often in those subjected to water
      stress. These tissues were located inside the epidermis, resembling a web of
      collapsible-cell groups surrounding turgid cells, vascular bundles, and spanned
      across the pith. Occasionally the groups formed a continuum stretching from the
      epidermis towards the vasculature. Integrating the morphology and the anatomy in
      a developmental context as a response to environmental conditions provides a
      better understanding of the organism's dynamics, adaptation, and plasticity.

PMID- 22479482
TI  - ApoTransferrin: dual role on adult subventricular zone-derived neurospheres.
AB  - Neural stem and progenitor cells (NSC/NPCs) are multipotent self-renewing cells
      that are able to generate neurons, astrocytes and oligodendrocytes (OLs) within
      the adult central nervous system. We cultured NSC/NPCs from the rat
      subventricular zone as neurospheres (NS) and studied apoTransferrin (aTf) effects
      on oligodendroglial specification and maturation. Our findings suggest that aTf
      acts at different stages during progression from NSC to mature oligodendrocytes.
      On the one hand, an early event associated with the activation of NSC/NPCs
      proliferation and commitment toward the oligodendroglial fate, as indicated by
      increased BrdU incorporation, larger neurospheres production, and higher ability
      to generate OL precursors (OPCs) from undifferentiated cultures. On the other
      hand, aTf exposure during differentiating conditions favours OL maturation from
      OPCs by promoting OL morphological development. This evidence supports a key role
      of Tf on the generation of OL from NSC/NPCs and highlights its potential in
      demyelinating disorder treatment.

PMID- 22479484
TI  - Prevalence and determinants of khat (Catha edulis) chewing among high school
      students in eastern Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Use of psychoactive drugs such as khat leaves (Catha edulis) alter
      moods and emotional state and lead to adverse effects on the health and social
      life of users. Ethiopia is a major producer and exporter of khat in east Africa
      and the majority of the khat comes from the eastern part of the country, however,
      no studies have been conducted to investigate the habit in this area. This study
      was conducted to assess the prevalence and predictors of khat chewing among high
      school students in Harar, eastern Ethiopia. METHODOLOGY: The study was conducted
      among 1,890 secondary school students in Harar town in April 2010. A structured
      self-administered questionnaire was used for data collection. Descriptive
      statistics and logistic regression were performed to examine the prevalence and
      predictors of khat chewing. RESULT: The overall prevalence of khat chewing among
      the sample was 24.2% (95% CI 22.2%-26.2%). About 28.5% of females and 71.5% of
      males had chewed khat. Older age (OR 1.31; 95% CI 1.16-1.49), male gender (OR
      2.10; 95% CI 1.50-2.93), Muslim religion (OR 1.88; 95% CI 1.17-3.04), having
      friends who chewed khat (OR 7.93; 95% CI 5.40-11.64), and availability of someone
      with a similar habit in the family (OR 1.50; 95% CI 1.07-2.11) were found to be
      independent predictors of chewing. CONCLUSION: A significant proportion of
      students chew khat. The use of khat is significantly associated with age, gender,
      Muslim religion, peer influence and habit of family and other relatives among
      students. Measures such as educational campaigns need to be instituted to create
      awareness among school adolescents and their parents in order to reduce the
      prevalence of the habit and its adverse social and health consequences.

PMID- 22479483
TI  - Apoptotic effects of antilymphocyte globulins on human pro-inflammatory CD4+CD28-
      T-cells.
AB  - BACKGROUND: Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects
      in apoptosis have been investigated as markers of premature immuno-senescence in
      various immune-mediated diseases. In this study we evaluated the influence of
      polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T
      cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three
      colour fluorescence activated cell sorting analyses of peripheral blood
      mononuclear cells from 16 consecutive transplant recipients and short-term cell
      lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells
      decreased from 3.7 +/- 7.1% before to 0 +/- 0% six hours after ATG-F application
      (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 +/- 2.9% vs.
      3.9 +/- 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells,
      which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis
      was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl
      (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21
      hydrogensuccinate. ATG-F triggered CD25 expression and production of pro
      inflammatory cytokines, and induced down-regulation of the type 1 chemokine
      receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L
      predominately in CD4(+)CD28(-) T-cells. CONCLUSION: In summary, in vivo depletion
      of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was
      paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine
      receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the
      underlying mechanism.

PMID- 22479485
TI  - Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV
      reservoir seeding during acute HIV infection.
AB  - BACKGROUND: Limited knowledge exists on early HIV events that may inform
      preventive and therapeutic strategies. This study aims to characterize the
      earliest immunologic and virologic HIV events following infection and
      investigates the usage of a novel therapeutic strategy. METHODS AND FINDINGS: We
      prospectively screened 24,430 subjects in Bangkok and identified 40 AHI
      individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III,
      2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART
      (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were
      completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age
      was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected
      with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm(3). HIV RNA was
      5.5 log(10) copies/ml. Median total blood HIV DNA was higher in Fiebig III (550
      copy/10(6) PBMC) vs. Fiebig I (8 copy/10(6) PBMC) (p = 0.01) while the median
      %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p =
      0.0008). After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved
      in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted
      reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was
      undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T
      cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with
      less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from
      baseline to week 24 (14% vs. 71%, p = 0.02). CONCLUSIONS: Gut T cell depletion
      and HIV reservoir seeding increases with progression of AHI. MegaHAART was
      associated with immune restoration and reduced reservoir size. Our findings could
      inform research on strategies to achieve HIV drug-free remission.

PMID- 22479486
TI  - Kinetics of inclusion body formation and its correlation with the characteristics
      of protein aggregates in Escherichia coli.
AB  - The objective of the research was to understand the structural determinants
      governing protein aggregation into inclusion bodies during expression of
      recombinant proteins in Escherichia coli. Recombinant human growth hormone (hGH)
      and asparaginase were expressed as inclusion bodies in E.coli and the kinetics of
      aggregate formation was analyzed in details. Asparaginase inclusion bodies were
      of smaller size (200 nm) and the size of the aggregates did not increase with
      induction time. In contrast, the seeding and growth behavior of hGH inclusion
      bodies were found to be sequential, kinetically stable and the aggregate size
      increased from 200 to 800 nm with induction time. Human growth hormone inclusion
      bodies showed higher resistance to denaturants and proteinase K degradation in
      comparison to those of asparaginase inclusion bodies. Asparaginase inclusion
      bodies were completely solubilized at 2-3 M urea concentration and could be
      refolded into active protein, whereas 7 M urea was required for complete
      solubilization of hGH inclusion bodies. Both hGH and asparaginase inclusion
      bodies showed binding with amyloid specific dyes. In spite of its low beta-sheet
      content, binding with dyes was more prominent in case of hGH inclusion bodies
      than that of asparaginase. Arrangements of protein molecules present in the
      surface as well as in the core of inclusion bodies were similar. Hydrophobic
      interactions between partially folded amphiphillic and hydrophobic alpha-helices
      were found to be one of the main determinants of hGH inclusion body formation.
      Aggregation behavior of the protein molecules decides the nature and properties
      of inclusion bodies.

PMID- 22479487
TI  - CUP-1 is a novel protein involved in dietary cholesterol uptake in Caenorhabditis
      elegans.
AB  - Sterols transport and distribution are essential processes in all multicellular
      organisms. Survival of the nematode Caenorhabditis elegans depends on dietary
      absorption of sterols present in the environment. However the general mechanisms
      associated to sterol uptake in nematodes are poorly understood. In the present
      work we provide evidence showing that a previously uncharacterized transmembrane
      protein, designated Cholesterol Uptake Protein-1 (ChUP-1), [corrected] is
      involved in dietary cholesterol uptake in C. elegans. Animals lacking ChUP-1
      [corrected] showed hypersensitivity to cholesterol limitation and were unable to
      uptake cholesterol. A ChUP-1-GFP [corrected] fusion protein colocalized with
      cholesterol-rich vesicles, endosomes and lysosomes as well as the plasma
      membrane. Additionally, by FRET imaging, a direct interaction was found between
      the cholesterol analog DHE and the transmembrane "cholesterol
      recognition/interaction amino acid consensus" (CRAC) motif present in C. elegans
      ChUP-1. [corrected]. In-silico analysis identified two mammalian homologues of
      ChUP-1. [corrected]. Most interestingly, CRAC motifs are conserved in mammalian
      ChUP-1 [corrected] homologous. Our results suggest a role of ChUP-1 [corrected]
      in cholesterol uptake in C. elegans and open up the possibility for the existence
      of a new class of proteins involved in sterol absorption in mammals.

PMID- 22479488
TI  - No association of COMT (Val158Met) genotype with brain structure differences
      between men and women.
AB  - We examined the effect of the catechol-O-methyltransferase (COMT) Val158Met
      polymorphism (rs4680), on brain structure in a subset (N = 82) of general
      population members of the Northern Finland 1966 Birth Cohort, selected through a
      randomization procedure, aged 33-35. Optimised voxel-based morphometry was used
      to produce grey matter maps from each subject's high resolution T1 weighted brain
      magnetic resonance images, which were subsequently entered into a general linear
      model with COMT genotype as defined by Met allele loading, gender and genotype by
      gender interaction as independent variables. Additional analyses were carried out
      on grey matter volumes within the dorsal lateral pre-frontal cortex (DLPFC) to
      examine effects on overall DLPFC volume and also using the DLPFC as a mask for
      voxelwise analyses, as this is an area previously reported as associated with Met
      allele loading. We failed to find any statistically significant association with
      grey matter volume and Met allele loading in the COMT gene or interaction affects
      between COMT and gender in either the whole brain voxel-wise analysis or in the
      area of the DLPFC.

PMID- 22479489
TI  - CD4+CD25+ Regulatory T cell ontogeny and preferential migration to the cecal
      tonsils in chickens.
AB  - Thymic CD4(+)CD25(+) cells have regulatory-T-cell-like properties in chickens.
      This study examined the ontogeny of CD4(+)CD25(+) cells in the thymus and in
      peripheral compartments in chickens. CD4(+)CD25(+) cells started to appear in the
      thymus at day 15 of incubation (E15), although at low percentages. Expressed as a
      percentage of CD4(+) cells, CD4(+)CD25(+) cells increased (P<0.01) from 1.7% at
      E20 to 7.3% at 0 d post-hatch (D0). CD4(+)CD25(+) cells did not appear in the
      spleen or cecal tonsils of embryos. Expressed as a percentage of CD4(+) cells,
      CD4(+)CD25(+) cells increased (P<0.01) from 0% at D0 to 27% at D1 in cecal
      tonsils and from 0% at D0 to 11% at D1 in the spleen. Expressed as a percentage
      of all mononuclear cells, cecal tonsils at D1 had approximately 3.5-fold higher
      percentage of CD4(+)CD25(+) cells than the spleen at D1. CD4(+)CD25(+) cells from
      cecal tonsils of chicks at D1 were suppressive. CD4(+)CD25(+) cells from D0
      thymus, when injected back into MHC-compatible chicks, migrated to cecal tonsils
      and lungs and were detected until 10 d post-injection. CD4(+)CD25(+) cells from
      cecal tonsils had a higher (P = 0.01) relative amount of CCR9 mRNA than
      CD4(+)CD25(+) cells from the thymus. It could be concluded that in chickens
      CD4(+)CD25(+) cells migrate from the thymus immediately post-hatch and
      preferentially colonize the gut associated lymphoid tissues. CD4(+)CD25(+) cells'
      preferential migration to cecal tonsils is likely directed through the CCR9
      pathway in chickens.

PMID- 22479490
TI  - The multipartite mitochondrial genome of Liposcelis bostrychophila: insights into
      the evolution of mitochondrial genomes in bilateral animals.
AB  - Booklice (order Psocoptera) in the genus Liposcelis are major pests to stored
      grains worldwide and are closely related to parasitic lice (order Phthiraptera).
      We sequenced the mitochondrial (mt) genome of Liposcelis bostrychophila and found
      that the typical single mt chromosome of bilateral animals has fragmented into
      and been replaced by two medium-sized chromosomes in this booklouse; each of
      these chromosomes has about half of the genes of the typical mt chromosome of
      bilateral animals. These mt chromosomes are 8,530 bp (mt chromosome I) and 7,933
      bp (mt chromosome II) in size. Intriguingly, mt chromosome I is twice as abundant
      as chromosome II. It appears that the selection pressure for compact mt genomes
      in bilateral animals favors small mt chromosomes when small mt chromosomes co
      exist with the typical large mt chromosomes. Thus, small mt chromosomes may have
      selective advantages over large mt chromosomes in bilateral animals. Phylogenetic
      analyses of mt genome sequences of Psocodea (i.e. Psocoptera plus Phthiraptera)
      indicate that: 1) the order Psocoptera (booklice and barklice) is paraphyletic;
      and 2) the order Phthiraptera (the parasitic lice) is monophyletic. Within
      parasitic lice, however, the suborder Ischnocera is paraphyletic; this differs
      from the traditional view that each suborder of parasitic lice is monophyletic.

PMID- 22479491
TI  - Long-term mortality of patients with septic ocular or central nervous system
      complications from pyogenic liver abscess: a population-based study.
AB  - BACKGROUND: Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or
      central nervous system (CNS) complications derived from PLA can result in
      catastrophic disability. We investigated the epidemiology and long-term prognosis
      of PLA patients with septic ocular or CNS complications over an 8-year period.
      METHODOLOGY/PRINCIPAL FINDINGS: We extracted 21,307 patients with newly diagnosed
      PLA from a nationwide health registry in Taiwan between 2000 and 2007. The
      frequency of and risk factors for PLA with septic ocular or CNS complications
      were determined. The 2-year survival of these patients was compared between those
      with and without septic ocular or CNS complications. Septic ocular or CNS
      complications accounted for 2.1% of all PLA patients. Age and the Charlson
      comorbidity index were significantly lower in PLA patients with ocular or CNS
      complications than those without. Diabetes and age <65 years were independent
      predictors of septic ocular or CNS complications. The 2-year mortality of
      patients with septic ocular or CNS complications was similar to those without
      complications (24.8% vs. 27.5%, p = 0.502). However, among patients <65 years old
      and a Charlson index <= 1, the 2-year mortality was significantly higher in those
      with than without complications (18.6% vs. 11.8%, p = 0.001).
      CONCLUSIONS/SIGNIFICANCE: Physicians should recognize that catastrophic
      disability due to ocular or neurological complications from PLA could lead to a
      poor long-term prognosis, and should follow-up these patients more closely.

PMID- 22479493
TI  - Multicopper oxidase-3 is a laccase associated with the peritrophic matrix of
      Anopheles gambiae.
AB  - The multicopper oxidase (MCO) family of enzymes includes laccases, which oxidize
      a broad range of substrates including polyphenols and phenylendiamines;
      ferroxidases, which oxidize ferrous iron; and several other oxidases with
      specific substrates such as ascorbate, bilirubin or copper. The genome of
      Anopheles gambiae, a species of mosquito, encodes five putative multicopper
      oxidases. Of these five, only AgMCO2 has known enzymatic and physiological
      functions: it is a highly conserved laccase that functions in cuticle
      pigmentation and tanning by oxidizing dopamine and dopamine derivatives. AgMCO3
      is a mosquito-specific gene that is expressed predominantly in adult midguts and
      Malpighian tubules. To determine its enzymatic function, we purified recombinant
      AgMCO3 and analyzed its activity. AgMCO3 oxidized hydroquinone (a p-diphenol),
      the five o-diphenols tested, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic
      acid) (ABTS), and p-phenylenediamine, but not ferrous iron. The catalytic
      efficiencies of AgMCO3 were similar to those of cuticular laccases (MCO2
      orthologs), except that AgMCO3 oxidized all of the phenolic substrates with
      similar efficiencies whereas the MCO2 isoforms were less efficient at oxidizing
      catechol or dopa. These results demonstrate that AgMCO3 can be classified as a
      laccase and suggest that AgMCO3 has a somewhat broader substrate specificity than
      MCO2 orthologs. In addition, we observed AgMCO3 immunoreactivity in the
      peritrophic matrix, which functions as a selective barrier between the blood meal
      and midgut epithelial cells, protecting the midgut from mechanical damage,
      pathogens, and toxic molecules. We propose that AgMCO3 may oxidize toxic
      molecules in the blood meal leading to detoxification or to cross-linking of the
      molecules to the peritrophic matrix, thus targeting them for excretion.

PMID- 22479492
TI  - The lid domain of Caenorhabditis elegans Hsc70 influences ATP turnover, cofactor
      binding and protein folding activity.
AB  - Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy
      of ATP hydrolysis to alter the folding state of its client proteins. In contrast
      to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C.
      elegans (CeHsc70) has not been studied to date.We find that CeHsc70 is
      characterized by a high ATP turnover rate and limited by post-hydrolysis
      nucleotide exchange. This rate-limiting step is defined by the helical lid domain
      at the C-terminus. A certain truncation in this domain (CeHsc70-Delta545) reduces
      the turnover rate and renders the hydrolysis step rate-limiting. The helical lid
      domain also affects cofactor affinities as the lidless mutant CeHsc70-Delta512
      binds more strongly to DNJ-13, forming large protein complexes in the presence of
      ATP. Despite preserving the ability to hydrolyze ATP and interact with its
      cofactors DNJ-13 and BAG-1, the truncation of the helical lid domain leads to the
      loss of all protein folding activity, highlighting the requirement of this domain
      for the functionality of the nematode's Hsc70 protein.

PMID- 22479494
TI  - Coreferentiality: a new method for the hypothesis-based analysis of phenotypes
      characterized by multivariate data.
AB  - Many multifactorial biologic effects, particularly in the context of complex
      human diseases, are still poorly understood. At the same time, the systematic
      acquisition of multivariate data has become increasingly easy. The use of such
      data to analyze and model complex phenotypes, however, remains a challenge. Here,
      a new analytic approach is described, termed coreferentiality, together with an
      appropriate statistical test. Coreferentiality is the indirect relation of two
      variables of functional interest in respect to whether they parallel each other
      in their respective relatedness to multivariate reference data, which can be
      informative for a complex effect or phenotype. It is shown that the power of
      coreferentiality testing is comparable to multiple regression analysis,
      sufficient even when reference data are informative only to a relatively small
      extent of 2.5%, and clearly exceeding the power of simple bivariate correlation
      testing. Thus, coreferentiality testing uses the increased power of multivariate
      analysis, however, in order to address a more straightforward interpretable
      bivariate relatedness. Systematic application of this approach could
      substantially improve the analysis and modeling of complex phenotypes,
      particularly in the context of human study where addressing functional hypotheses
      by direct experimentation is often difficult.

PMID- 22479495
TI  - The protein partners of GTP cyclohydrolase I in rat organs.
AB  - OBJECTIVE: GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for
      tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic
      target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The
      endogenous GCH1-interacting partners have not been identified. Here, we
      determined endogenous GCH1-interacting proteins in rat. METHODS AND RESULTS: A
      pulldown and proteomics approach were used to identify GCH1 interacting proteins
      in rat liver, brain, heart and kidney. We demonstrated that GCH1 interacts with
      at least 17 proteins including GTP cyclohydrolase I feedback regulatory protein
      (GFRP) in rat liver by affinity purification followed by proteomics and validated
      six protein partners in liver, brain, heart and kidney by immunoblotting. GCH1
      interacts with GFRP and very long-chain specific acyl-CoA dehydrogenase in the
      liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A
      member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and
      eukaryotic translation initiation factor 3 subunit I (EIF3I) in all organs
      tested. Furthermore, GCH1 associates with mitochondrial proteins and GCH1 itself
      locates in mitochondria. CONCLUSION: GCH1 interacts with proteins in an organ
      dependant manner and EIF3I might be a general regulator of GCH1. Our finding
      indicates GCH1 might have broader functions beyond tetrahydrobiopterin
      biosynthesis.

PMID- 22479497
TI  - Zipf's law in short-time timbral codings of speech, music, and environmental
      sound signals.
AB  - Timbre is a key perceptual feature that allows discrimination between different
      sounds. Timbral sensations are highly dependent on the temporal evolution of the
      power spectrum of an audio signal. In order to quantitatively characterize such
      sensations, the shape of the power spectrum has to be encoded in a way that
      preserves certain physical and perceptual properties. Therefore, it is common
      practice to encode short-time power spectra using psychoacoustical frequency
      scales. In this paper, we study and characterize the statistical properties of
      such encodings, here called timbral code-words. In particular, we report on rank
      frequency distributions of timbral code-words extracted from 740 hours of audio
      coming from disparate sources such as speech, music, and environmental sounds.
      Analogously to text corpora, we find a heavy-tailed Zipfian distribution with
      exponent close to one. Importantly, this distribution is found independently of
      different encoding decisions and regardless of the audio source. Further analysis
      on the intrinsic characteristics of most and least frequent code-words reveals
      that the most frequent code-words tend to have a more homogeneous structure. We
      also find that speech and music databases have specific, distinctive code-words
      while, in the case of the environmental sounds, this database-specific code-words
      are not present. Finally, we find that a Yule-Simon process with memory provides
      a reasonable quantitative approximation for our data, suggesting the existence of
      a common simple generative mechanism for all considered sound sources.

PMID- 22479496
TI  - Compensatory T-cell regulation in unaffected relatives of SLE patients, and
      opposite IL-2/CD25-mediated effects suggested by coreferentiality modeling.
AB  - In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate
      over years before disease manifestation. Unaffected relatives of SLE patients
      frequently share a sustained production of autoantibodies with indiscriminable
      specificity, usually without ever acquiring the disease. We studied relations of
      IgG autoantibody profiles and peripheral blood activated regulatory T-cells
      (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90%
      Foxp3(+). We found consistent positive correlations of broad-range as well as
      specific SLE-associated IgG with aTreg frequencies within unaffected relatives,
      but not patients or unrelated controls. Our interpretation: unaffected relatives
      with shared genetic factors compensated pathogenic effects by aTregs engaged in
      parallel with the individual autoantibody production. To study this further, we
      applied a novel analytic approach named coreferentiality that tests the indirect
      relatedness of parameters in respect to multivariate phenotype data. Results show
      that independently of their direct correlation, aTreg frequencies and specific
      SLE-associated IgG were likely functionally related in unaffected relatives: they
      significantly parallelled each other in their relations to broad-range immunoblot
      autoantibody profiles. In unaffected relatives, we also found coreferential
      effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25
      functional genetic effects constructed by coreferentiality maximization suggests
      that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives,
      had an opposed effect in SLE patients, presumably triggering primarily T-effector
      cells in this group. Coreferentiality modeling as we do it here could also be
      useful in other contexts, particularly to explore combined functional genetic
      effects.

PMID- 22479498
TI  - Use of arthropod rarity for area prioritisation: insights from the Azorean
      Islands.
AB  - We investigated the conservation concern of Azorean forest fragments and the
      entire Terceira Island surface using arthropod species vulnerability as defined
      by the Kattan index, which is based on species rarity. Species rarity was
      evaluated according to geographical distribution (endemic vs. non endemic
      species), habitat specialization (distribution across biotopes) and population
      size (individuals collected in standardized samples). Geographical rarity was
      considered at 'global' scale (species endemic to the Azorean islands) and
      'regional' scale (single island endemics). Measures of species vulnerability were
      combined into two indices of conservation concern for each forest fragment: (1)
      the Biodiversity Conservation Concern index, BCC, which reflects the average
      rarity score of the species present in a site, and (2) one proposed here and
      termed Biodiversity Conservation Weight, BCW, which reflects the sum of rarity
      scores of the same species assemblage. BCW was preferable to prioritise the areas
      with highest number of vulnerable species, whereas BCC helped the identification
      of areas with few, but highly threatened species due to a combination of
      different types of rarity.A novel approach is introduced in which BCC and BCW
      indices were also adapted to deal with probabilities of occurrence instead of
      presence/absence data. The new probabilistic indices, termed pBCC and pBCW, were
      applied to Terceira Island for which we modelled species distributions to
      reconstruct species occurrence with different degree of probability also in areas
      from which data were not available. The application of the probabilistic indices
      revealed that some island sectors occupied by secondary vegetation, and hence not
      included in the current set of protected areas, may in fact host some rare
      species. This result suggests that protecting marginal non-natural areas which
      are however reservoirs of vulnerable species may also be important, especially
      when areas with well preserved primary habitats are scarce.

PMID- 22479499
TI  - Thinking about eating food activates visual cortex with reduced bilateral
      cerebellar activation in females with anorexia nervosa: an fMRI study.
AB  - BACKGROUND: Women with anorexia nervosa (AN) have aberrant cognitions about food
      and altered activity in prefrontal cortical and somatosensory regions to food
      images. However, differential effects on the brain when thinking about eating
      food between healthy women and those with AN is unknown. METHODS: Functional
      magnetic resonance imaging (fMRI) examined neural activation when 42 women
      thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24
      age-matched controls (HC). RESULTS: Group contrasts between HC and AN revealed
      reduced activation in AN in the bilateral cerebellar vermis, and increased
      activation in the right visual cortex. Preliminary comparisons between AN
      subtypes and healthy controls suggest differences in cortical and limbic regions.
      CONCLUSIONS: These preliminary data suggest that thinking about eating food shown
      in images increases visual and prefrontal cortical neural responses in females
      with AN, which may underlie cognitive biases towards food stimuli and ruminations
      about controlling food intake. Future studies are needed to explicitly test how
      thinking about eating activates restraint cognitions, specifically in those with
      restricting vs. binge-purging AN subtypes.

PMID- 22479500
TI  - Women born preterm or with inappropriate weight for gestational age are at risk
      of subsequent gestational diabetes and pre-eclampsia.
AB  - INTRODUCTION: Low birthweight, which can be caused by inappropriate intrauterine
      growth or prematurity, is associated with development of gestational diabetes
      mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects
      of prematurity and inappropriate intrauterine growth remain uncertain. METHODS:
      Through nation-wide registries we identified all Danish mothers in the years 1989
      2007. Two separate cohorts consisting mothers born 1974-1977 (n = 84219) and 1978
      1981 (n = 32376) were studied, due to different methods of registering
      birthweight and gestational age in the two periods. Data was linked with
      information on GDM, pre-eclampsia and education. RESULTS: In a multivariate
      logistic regression model the odds of developing GDM was increased by 5-7% for
      each week the mother was born before term (p = 0.018 for 1974-1977, p = 0.048 for
      1978-1981), while the odds were increased by 13-17% for each standard deviation
      (SD) reduction in birthweight for gestational age for those who were small or
      normal for gestational age (p<0.0001 and p = 0.035) and increased by 118-122% for
      each SD increase above the normal range (p<0.0001 and p = 0.024). The odds of pre
      eclampsia was increased by 3-5% for each week the mother was born before term (p
      = 0.064 and p = 0.04), while the odds were increased 11-12% for each SD reduction
      in birthweight for gestational age (p<0.0001 and p = 0.0002). CONCLUSION: In this
      cohort of young Danish mothers, being born premature or with increasingly low
      birthweight for gestational age was associated with an increased risk of GDM and
      pre-eclampsia in adulthood, while increasingly high birthweight for gestational
      age was associated with an increased risk of GDM and a decreased risk of pre
      eclampsia. Inappropriate weight for gestational age was a more important risk
      factor than prematurity.

PMID- 22479501
TI  - Central glucocorticoid administration promotes weight gain and increased 11beta
      hydroxysteroid dehydrogenase type 1 expression in white adipose tissue.
AB  - Glucocorticoids (GCs) are involved in multiple metabolic processes, including the
      regulation of insulin sensitivity and adipogenesis. Their action partly depends
      on their intracellular activation by 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1). We previously demonstrated that central GC administration promotes
      hyperphagia, body weight gain, hyperinsulinemia and marked insulin resistance at
      the level of skeletal muscles. Similar dysfunctions have been reported to occur
      upon specific overexpression of 11beta-HSD1 in adipose tissue. The aim of the
      present study was therefore to determine whether the effects of central GC
      infusion may enhance local GC activation in white adipose tissue. Male Wistar and
      Sprague Dawley (SD) rats were intracerebroventricularly infused with GCs for 2 to
      3 days. Body weight, food intake and metabolic parameters were measured, and
      expression of enzymes regulating 11beta-HSD1, as well as that of genes regulated
      by GCs, were quantified. Central GC administration induced a significant increase
      in body weight gain and in 11beta-HSD1 and resistin expression in adipose tissue.
      A decrease 11beta-HSD1 expression was noticed in the liver of SD rats, as a
      partial compensatory mechanism. Such effects of GCs are centrally elicited. This
      model of icv dexamethasone infusion thus appears to be a valuable acute model,
      that helps delineating the initial metabolic defects occurring in obesity. An
      impaired downregulation of intracellular GC activation in adipose tissue may be
      important for the development of insulin resistance.

PMID- 22479502
TI  - Near-infrared fluorescence imaging of mammalian cells and xenograft tumors with
      SNAP-tag.
AB  - Fluorescence in the near-infrared (NIR) spectral region is suitable for in vivo
      imaging due to its reduced background and high penetration capability compared to
      visible fluorescence. SNAP(f) is a fast-labeling variant of SNAP-tag that reacts
      with a fluorescent dye-conjugated benzylguanine (BG) substrate, leading to
      covalent attachment of the fluorescent dye to the SNAP(f). This property makes
      SNAP(f) a valuable tool for fluorescence imaging. The NIR fluorescent substrate
      BG-800, a conjugate between BG and IRDye 800CW, was synthesized and characterized
      in this study. HEK293, MDA-MB-231 and SK-OV-3 cells stably expressing SNAP(f)
      Beta-2 adrenergic receptor (SNAP(f)-ADRbeta2) fusion protein were created. The
      ADRbeta2 portion of the protein directs the localization of the protein to the
      cell membrane. The expression of SNAP(f)-ADRbeta2 in the stable cell lines was
      confirmed by the reaction between BG-800 substrate and cell lysates. Microscopic
      examination confirmed that SNAP(f)-ADRbeta2 was localized on the cell membrane.
      The signal intensity of the labeled cells was dependent on the BG-800
      concentration. In vivo imaging study showed that BG-800 could be used to
      visualize xenograph tumors expressing SNAP(f)-ADRbeta2. However, the background
      signal was relatively high, which may be a reflection of non-specific
      accumulation of BG-800 in the skin. To address the background issue, quenched
      substrates that only fluoresce upon reaction with SNAP-tag were synthesized and
      characterized. Although the fluorescence was successfully quenched, in vivo
      imaging with the quenched substrate CBG-800-PEG-QC1 failed to visualize the
      SNAP(f)-ADRbeta2 expressing tumor, possibly due to the reduced reaction rate.
      Further improvement is needed to apply this system for in vivo imaging.

PMID- 22479503
TI  - SEPTIN12 genetic variants confer susceptibility to teratozoospermia.
AB  - It is estimated that 10-15% of couples are infertile and male factors account for
      about half of these cases. With the advent of intracytoplasmic sperm injection
      (ICSI), many infertile men have been able to father offspring. However,
      teratozoospermia still remains a big challenge to tackle. Septins belong to a
      family of cytoskeletal proteins with GTPase activity and are involved in various
      biological processes e.g. morphogenesis, compartmentalization, apoptosis and
      cytokinesis. SEPTIN12, identified by c-DNA microarray analysis of infertile men,
      is exclusively expressed in the post meiotic male germ cells.
      Septin12(+/+)/Septin12(+/-) chimeric mice have multiple reproductive defects
      including the presence of immature sperm in the semen, and sperm with bent neck
      (defect of the annulus) and nuclear DNA damage. These facts make SEPTIN12 a
      potential sterile gene in humans. In this study, we sequenced the entire coding
      region of SEPTIN12 in infertile men (n = 160) and fertile controls (n = 200) and
      identified ten variants. Among them is the c.474 G>A variant within exon 5 that
      encodes part of the GTP binding domain. The variant creates a novel splice donor
      site that causes skipping of a portion of exon 5, resulting in a truncated
      protein lacking the C-terminal half of SEPTIN12. Most individuals homozygous for
      the c.474 A allele had teratozoospermia (abnormal sperm <14%) and their sperm
      showed bent tail and de-condensed nucleus with significant DNA damage. Ex vivo
      experiment showed truncated SEPT12 inhibits filament formation in a dose
      dependent manner. This study provides the first causal link between SEPTIN12
      genetic variant and male infertility with distinctive sperm pathology. Our
      finding also suggests vital roles of SEPT12 in sperm nuclear integrity and tail
      development.

PMID- 22479504
TI  - A single gene target of an ETS-family transcription factor determines neuronal
      CO2-chemosensitivity.
AB  - Many animals possess neurons specialized for the detection of carbon dioxide
      (CO(2)), which acts as a cue to elicit behavioral responses and is also an
      internally generated product of respiration that regulates animal physiology. In
      many organisms how such neurons detect CO(2) is poorly understood. We report here
      a mechanism that endows C. elegans neurons with the ability to detect CO(2). The
      ETS-5 transcription factor is necessary for the specification of CO(2)-sensing
      BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a
      receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5
      in CO(2)-detection and transforms neurons into CO(2)-sensing neurons. Because ETS
      5 and GCY-9 are members of gene families that are conserved between nematodes and
      vertebrates, a similar mechanism might act in the specification of CO(2)-sensing
      neurons in other phyla.

PMID- 22479505
TI  - Physical and functional interaction of NCX1 and EAAC1 transporters leading to
      glutamate-enhanced ATP production in brain mitochondria.
AB  - Glutamate is emerging as a major factor stimulating energy production in CNS.
      Brain mitochondria can utilize this neurotransmitter as respiratory substrate and
      specific transporters are required to mediate the glutamate entry into the
      mitochondrial matrix. Glutamate transporters of the Excitatory Amino Acid
      Transporters (EAATs) family have been previously well characterized on the cell
      surface of neuronal and glial cells, representing the primary players for
      glutamate uptake in mammalian brain. Here, by using western blot, confocal
      microscopy and immunoelectron microscopy, we report for the first time that the
      Excitatory Amino Acid Carrier 1 (EAAC1), an EAATs member, is expressed in
      neuronal and glial mitochondria where it participates in glutamate-stimulated ATP
      production, evaluated by a luciferase-luciferin system. Mitochondrial metabolic
      response is counteracted when different EAATs pharmacological blockers or
      selective EAAC1 antisense oligonucleotides were used. Since EAATs are Na(+)
      dependent proteins, this raised the possibility that other transporters
      regulating ion gradients across mitochondrial membrane were required for
      glutamate response. We describe colocalization, mutual activity dependency,
      physical interaction between EAAC1 and the sodium/calcium exchanger 1 (NCX1) both
      in neuronal and glial mitochondria, and that NCX1 is an essential modulator of
      this glutamate transporter. Only NCX1 activity is crucial for such glutamate
      stimulated ATP synthesis, as demonstrated by pharmacological blockade and
      selective knock-down with antisense oligonucleotides. The EAAC1/NCX1-dependent
      mitochondrial response to glutamate may be a general and alternative mechanism
      whereby this neurotransmitter sustains ATP production, since we have documented
      such metabolic response also in mitochondria isolated from heart. The data
      reported here disclose a new physiological role for mitochondrial NCX1 as the key
      player in glutamate-induced energy production.

PMID- 22479506
TI  - Xylosyltransferase-I regulates glycosaminoglycan synthesis during the pathogenic
      process of human osteoarthritis.
AB  - Loss of glycosaminoglycan (GAG) chains of proteoglycans (PGs) is an early event
      of osteoarthritis (OA) resulting in cartilage degradation that has been
      previously demonstrated in both huma and experimental OA models. However, the
      mechanism of GAG loss and the role of xylosyltransferase-I (XT-I) that initiates
      GAG biosynthesis onto PG molecules in the pathogenic process of human OA are
      unknown. In this study, we have characterized XT-I expression and activity
      together with GAG synthesis in human OA cartilage obtained from different regions
      of the same joint, defined as "normal", "late-stage" or adjacent to "late-stage".
      The results showed that GAG synthesis and content increased in cartilage from
      areas flanking OA lesions compared to cartilage from macroscopically "normal"
      unaffected regions, while decreased in "late-stage" OA cartilage lesions. This
      increase in anabolic state was associated with a marked upregulation of XT-I
      expression and activity in cartilage "next to lesion" while a decrease in the
      "late-stage" OA cartilage. Importantly, XT-I inhibition by shRNA or forced
      expression with a pCMV-XT-I construct correlated with the modulation of GAG
      anabolism in human cartilage explants. The observation that XT-I gene expression
      was down-regulated by IL-1beta and up-regulated by TGF-beta1 indicates that these
      cytokines may play a role in regulating GAG content in human OA. Noteworthy,
      expression of IL-1beta receptor (IL-1R1) was down-regulated whereas that of TGF
      beta1 was up-regulated in early OA cartilage. Theses observations may account for
      upregulation of XT-I and sustained GAG synthesis prior to the development of
      cartilage lesions during the pathogenic process of OA.

PMID- 22479507
TI  - Leishmania amazonensis arginase compartmentalization in the glycosome is
      important for parasite infectivity.
AB  - In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L
      arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1).
      Previous studies in L. major and L. mexicana showed that ARG is essential for in
      vitro growth in the absence of polyamines and needed for full infectivity in
      animal infections. The ARG protein is normally found within the parasite
      glycosome, and here we examined whether this localization is required for
      survival and infectivity. First, the localization of L. amazonensis ARG in the
      glycosome was confirmed in both the promastigote and amastigote stages. As in
      other species, arg(-) L. amazonensis required putrescine for growth and presented
      an attenuated infectivity. Restoration of a wild type ARG to the arg(-) mutant
      restored ARG expression, growth and infectivity. In contrast, restoration of a
      cytosol-targeted ARG lacking the glycosomal SKL targeting sequence (argDeltaSKL)
      restored growth but failed to restore infectivity. Further study showed that the
      ARGDeltaSKL protein was found in the cytosol as expected, but at very low levels.
      Our results indicate that the proper compartmentalization of L. amazonensis
      arginase in the glycosome is important for enzyme activity and optimal
      infectivity. Our conjecture is that parasite arginase participates in a complex
      equilibrium that defines the fate of L-arginine and that its proper subcellular
      location may be essential for this physiological orchestration.

PMID- 22479508
TI  - Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin
      aldosterone system associated epithelial-to-mesenchymal transition.
AB  - BACKGROUND: Uremic toxins are considered to have a determinant pathological role
      in the progression of chronic kidney disease. The aim of this study was to define
      the putative pathological roles of the renal renin-angiotensin-aldosterone system
      (RAAS) and renal tubular epithelial-to-mesenchymal transition (EMT) in kidney
      fibrosis induced by (indoxyl sulfate) IS and (p-cresol sulfate) PCS. METHODS:
      Mouse proximal renal tubular cells (PKSV-PRs) treated with IS or PCS were used.
      Half-nephrectomized B-6 mice were treated with IS or PCS for 4 weeks. In the
      losartan treatment study, the study animal was administrated with IS+losartan or
      PCS+losartan for 4 weeks. RESULTS: IS and PCS significantly activated the
      intrarenal RAAS by increasing renin, angiotensinogen, and angiotensin 1 (AT1)
      receptor expression, and decreasing AT2 receptor expression in vitro and in vivo.
      IS and PCS significantly increased transforming growth factor-beta1 (TGF-beta1)
      expression and activated the TGF-beta pathway by increasing Smad2/Smad2-P,
      Smad3/Smad3-P, and Smad4 expression. The expression of the EMT-associated
      transcription factor Snail was increased by IS and PCS treatment. IS and PCS
      induced the phenotype of EMT-like transition in renal tubules by increasing the
      expression of fibronectin and alpha-smooth muscle actin and decreasing the
      expression of E-cadherin. Losartan significantly attenuated the expression of TGF
      beta1 and Snail, and decreased kidney fibrosis induced by IS and PCS in vivo.
      CONCLUSION: Activating the renal RAAS/TGF-beta pathway has an important
      pathological role in chronic kidney injury caused by IS and PCS. IS and PCS may
      increase Snail expression and induce EMT-like transition.

PMID- 22479509
TI  - A programmable Escherichia coli consortium via tunable symbiosis.
AB  - Synthetic microbial consortia that can mimic natural systems have the potential
      to become a powerful biotechnology for various applications. One highly desirable
      feature of these consortia is that they can be precisely regulated. In this work
      we designed a programmable, symbiotic circuit that enables continuous tuning of
      the growth rate and composition of a synthetic consortium. We implemented our
      general design through the cross-feeding of tryptophan and tyrosine by two E.
      coli auxotrophs. By regulating the expression of genes related to the export or
      production of these amino acids, we were able to tune the metabolite exchanges
      and achieve a wide range of growth rates and strain ratios. In addition, by
      inverting the relationship of growth/ratio vs. inducer concentrations, we were
      able to "program" the co-culture for pre-specified attributes with the proper
      addition of inducing chemicals. This programmable proof-of-concept circuit or its
      variants can be applied to more complex systems where precise tuning of the
      consortium would facilitate the optimization of specific objectives, such as
      increasing the overall efficiency of microbial production of biofuels or
      pharmaceuticals.

PMID- 22479510
TI  - Territorial dynamics and stable home range formation for central place foragers.
AB  - Uncovering the mechanisms behind territory formation is a fundamental problem in
      behavioural ecology. The broad nature of the underlying conspecific avoidance
      processes are well documented across a wide range of taxa. Scent marking in
      particular is common to a large range of terrestrial mammals and is known to be
      fundamental for communication. However, despite its importance, exact
      quantification of the time-scales over which scent cues and messages persist
      remains elusive. Recent work by the present authors has begun to shed light on
      this problem by modelling animals as random walkers with scent-mediated
      interaction processes. Territories emerge as dynamic objects that continually
      change shape and slowly move without settling to a fixed location. As a
      consequence, the utilisation distribution of such an animal results in a slowly
      increasing home range, as shown for urban foxes (Vulpes vulpes). For certain
      other species, however, home ranges reach a stable state. The present work shows
      that stable home ranges arise when, in addition to scent-mediated conspecific
      avoidance, each animal moves as a central place forager. That is, the animal's
      movement has a random aspect but is also biased towards a fixed location, such as
      a den or nest site. Dynamic territories emerge but the probability distribution
      of the territory border locations reaches a steady state, causing stable home
      ranges to emerge from the territorial dynamics. Approximate analytic expressions
      for the animal's probability density function are derived. A programme is given
      for using these expressions to quantify both the strength of the animal's
      movement bias towards the central place and the time-scale over which scent
      messages persist. Comparisons are made with previous theoretical work modelling
      central place foragers with conspecific avoidance. Some insights into the
      mechanisms behind allometric scaling laws of animal space use are also given.

PMID- 22479511
TI  - Response of methicillin-resistant Staphylococcus aureus to amicoumacin A.
AB  - Amicoumacin A exhibits strong antimicrobial activity against methicillin
      resistant Staphylococcus aureus (MRSA), hence we sought to uncover its mechanism
      of action. Genome-wide transcriptome analysis of S. aureus COL in response to
      amicoumacin A showed alteration in transcription of genes specifying several
      cellular processes including cell envelope turnover, cross-membrane transport,
      virulence, metabolism, and general stress response. The most highly induced gene
      was lrgA, encoding an antiholin-like product, which is induced in cells
      undergoing a collapse of Deltapsi. Consistent with the notion that LrgA modulates
      murein hydrolase activity, COL grown in the presence of amicoumacin A showed
      reduced autolysis, which was primarily caused by lower hydrolase activity. To
      gain further insight into the mechanism of action of amicoumacin A, a whole
      genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated
      by a serial passage method was carried out. Single point mutations generating
      codon substitutions were uncovered in ksgA (encoding RNA dimethyltransferase),
      fusA (elongation factor G), dnaG (primase), lacD (tagatose 1,6-bisphosphate
      aldolase), and SACOL0611 (a putative glycosyl transferase). The codon
      substitutions in EF-G that cause amicoumacin A resistance and fusidic acid
      resistance reside in separate domains and do not bring about cross resistance.
      Taken together, these results suggest that amicoumacin A might cause perturbation
      of the cell membrane and lead to energy dissipation. Decreased rates of cellular
      metabolism including protein synthesis and DNA replication in resistant strains
      might allow cells to compensate for membrane dysfunction and thus increase cell
      survivability.

PMID- 22479512
TI  - Identification of chromosomal genes in Yersinia pestis that influence type III
      secretion and delivery of Yops into target cells.
AB  - Pathogenic Yersinia species possess a type III secretion system, which is
      required for the delivery of effector Yop proteins into target cells during
      infection. Genes encoding the type III secretion machinery, its substrates, and
      several regulatory proteins all reside on a 70-Kb virulence plasmid. Genes
      encoded in the chromosome of yersiniae are thought to play important roles in
      bacterial perception of host environments and in the coordinated activation of
      the type III secretion pathway. Here, we investigate the contribution of
      chromosomal genes to the complex regulatory process controlling type III
      secretion in Yersinia pestis. Using transposon mutagenesis, we identified five
      chromosomal genes required for expression or secretion of Yops in laboratory
      media. Four out of the five chromosomal mutants were defective to various extents
      at injecting Yops into tissue culture cells. Interestingly, we found one mutant
      that was not able to secrete in vitro but was fully competent for injecting Yops
      into host cells, suggesting independent mechanisms for activation of the
      secretion apparatus. When tested in a mouse model of plague disease, three
      mutants were avirulent, whereas two strains were severely attenuated. Together
      these results demonstrate the importance of Y. pestis chromosomal genes in the
      proper function of type III secretion and in the pathogenesis of plague.

PMID- 22479513
TI  - Tyrosine phosphorylation of the E3 ubiquitin ligase TRIM21 positively regulates
      interaction with IRF3 and hence TRIM21 activity.
AB  - Patients suffering from Systemic Lupus Erythematous (SLE) have elevated type I
      interferon (IFN) levels which correlate with disease activity and severity.
      TRIM21, an autoantigen associated with SLE, has been identified as an ubiquitin
      E3 ligase that targets the transcription factor IRF3 in order to turn off and
      limit type I IFN production following detection of viral and bacterial infection
      by Toll Like Receptors (TLRs). However, how the activity of TRIM21 is regulated
      downstream of TLRs is unknown. In this study we demonstrate that TRIM21 is
      tyrosine phosphorylated following TLR3 and TLR4 stimulation, suggesting that its
      activity is potentially regulated by tyrosine phosphorylation. Using Netphos, we
      have identified three key tyrosines that are strongly predicted to be
      phosphorylated, two of which are conserved between the human and murine forms of
      TRIM21, at residues 343, 388, and 393, all of which have been mutated from
      tyrosine to phenylalanine (Y343F, Y388F, and Y393F). We have observed that
      tyrosine phosphorylation of TRIM21 only occurs in the substrate binding PRY/SPRY
      domain, and that Y393, and to a lesser extent, Y388 are required for TRIM21 to
      function as a negative regulator of IFN-beta promoter activity. Further studies
      revealed that mutating Y393 to phenylalanine inhibits the ability of TRIM21 to
      interact with its substrate, IRF3, thus providing a molecular explanation for the
      lack of activity of Y393 on the IFN-beta promoter. Our data demonstrates a novel
      role for tyrosine phosphorylation in regulating the activity of TRIM21 downstream
      of TLR3 and TLR4. Given the pathogenic role of TRIM21 in systemic autoimmunity,
      these findings have important implications for the development of novel
      therapeutics.

PMID- 22479514
TI  - Resolving the sources of plasma glucose excursions following a glucose tolerance
      test in the rat with deuterated water and [U-13C]glucose.
AB  - Sources of plasma glucose excursions (PGE) following a glucose tolerance test
      enriched with [U-(13)C]glucose and deuterated water were directly resolved by
      (13)C and (2)H Nuclear Magnetic Resonance spectroscopy analysis of plasma glucose
      and water enrichments in rat. Plasma water (2)H-enrichment attained isotopic
      steady-state within 2-4 minutes following the load. The fraction of PGE derived
      from endogenous sources was determined from the ratio of plasma glucose position
      2 and plasma water (2)H-enrichments. The fractional gluconeogenic contributions
      to PGE were obtained from plasma glucose positions 2 and 5 (2)H-positional
      enrichment ratios and load contributions were estimated from plasma [U
      (13)C]glucose enrichments. At 15 minutes, the load contributed 26+/-5% of PGE
      while 14+/-2% originated from gluconeogenesis in healthy control rats. Between 15
      and 120 minutes, the load contribution fell whereas the gluconeogenic
      contribution remained constant. High-fat fed animals had significant higher 120
      minute blood glucose (173+/-6 mg/dL vs. 139+/-10 mg/dL, p<0.05) and gluconeogenic
      contributions to PGE (59+/-5 mg/dL vs. 38+/-3 mg/dL, p<0.01) relative to standard
      chow-fed controls. In summary, the endogenous and load components of PGE can be
      resolved during a glucose tolerance test and these measurements revealed that
      plasma glucose synthesis via gluconeogenesis remained active during the period
      immediately following a glucose load. In rats that were placed on high-fat diet,
      the development of glucose intolerance was associated with a significantly higher
      gluconeogenic contribution to plasma glucose levels after the load.

PMID- 22479515
TI  - Patterns of early gut colonization shape future immune responses of the host.
AB  - The most important trigger for immune system development is the exposure to
      microbial components immediately after birth. Moreover, targeted manipulation of
      the microbiota can be used to change host susceptibility to immune-mediated
      diseases. Our aim was to analyze how differences in early gut colonization
      patterns change the composition of the resident microbiota and future immune
      system reactivity. Germ-free (GF) mice were either inoculated by single oral
      gavage of caecal content or let colonized by co-housing with specific pathogen
      free (SPF) mice at different time points in the postnatal period. The microbiota
      composition was analyzed by denaturing gradient gel electrophoresis for 16S rRNA
      gene followed by principal component analysis. Furthermore, immune functions and
      cytokine concentrations were analyzed using flow cytometry, ELISA or multiplex
      bead assay. We found that a single oral inoculation of GF mice at three weeks of
      age permanently changed the gut microbiota composition, which was not possible to
      achieve at one week of age. Interestingly, the ex-GF mice inoculated at three
      weeks of age were also the only mice with an increased pro-inflammatory immune
      response. In contrast, the composition of the gut microbiota of ex-GF mice that
      were co-housed with SPF mice at different time points was similar to the gut
      microbiota in the barrier maintained SPF mice. The existence of a short GF
      postnatal period permanently changed levels of systemic regulatory T cells, NK
      and NKT cells, and cytokine production. In conclusion, a time window exists that
      enables the artificial colonization of GF mice by a single oral dose of caecal
      content, which may modify the future immune phenotype of the host. Moreover,
      delayed microbial colonization of the gut causes permanent changes in the immune
      system.

PMID- 22479516
TI  - HPV genotypes in high grade cervical lesions and invasive cervical carcinoma as
      detected by two commercial DNA assays, North Carolina, 2001-2006.
AB  - BACKGROUND: HPV typing using formalin fixed paraffin embedded (FFPE) cervical
      tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE
      specimens can negatively affect test results. This study aimed to evaluate 2
      commercial assays for HPV detection and typing using FFPE cervical specimens.
      METHODS: Four large North Carolina pathology laboratories provided FFPE specimens
      from 299 women ages18 and older diagnosed with cervical disease from 2001 to
      2006. For each woman, one diagnostic block was selected and unstained serial
      sections were prepared for DNA typing. Extracts from samples with residual lesion
      were used to detect and type HPV using parallel and serial testing algorithms
      with the Linear Array and LiPA HPV genotyping assays. FINDINGS: LA and LiPA
      concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any
      low-risk (LR) types, with significant differences in marginal proportions for
      HPV16, 51, 52, and any HR types. Discordant results were most often LiPA
      positive, LA-negative. The parallel algorithm yielded the highest prevalence of
      any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and
      serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using
      the serial algorithm, but the median number of HR types per woman (1) did not
      differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of
      invasive and >95% of pre-invasive lesions. The most common type was HPV16,
      followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens.
      Multiple HPV types were more common in lower grade lesions. CONCLUSIONS: We
      developed an efficient algorithm for testing and reporting results of two
      commercial assays for HPV detection and typing in FFPE specimens, and describe
      HPV type distribution in pre-invasive and invasive cervical lesions in a state
      based sample prior to HPV vaccine introduction.

PMID- 22479517
TI  - Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells
      via endocytosis.
AB  - BACKGROUND: Increasing evidence indicates that tumor endothelial cells (TEC)
      differ from normal endothelial cells (NEC). Our previous reports also showed that
      TEC were different from NEC. For example, TEC have chromosomal abnormality and
      proangiogenic properties such as high motility and proliferative activity.
      However, the mechanism by which TEC acquire a specific character remains unclear.
      To investigate this mechanism, we focused on tumor-derived microvesicles (TMV).
      Recent studies have shown that TMV contain numerous types of bioactive molecules
      and affect normal stromal cells in the tumor microenvironment. However, most of
      the functional mechanisms of TMV remain unclear. METHODOLOGY/PRINCIPAL FINDINGS:
      Here we showed that TMV isolated from tumor cells were taken up by NEC through
      endocytosis. In addition, we found that TMV promoted random motility and tube
      formation through the activation of the phosphoinositide 3-kinase/Akt pathway in
      NEC. Moreover, the effects induced by TMV were inhibited by the endocytosis
      inhibitor dynasore. Our results indicate that TMV could confer proangiogenic
      properties to NEC partly via endocytosis. CONCLUSION: We for the first time
      showed that endocytosis of TMV contributes to tumor angiogenesis. These findings
      offer new insights into cancer therapies and the crosstalk between tumor and
      endothelial cells mediated by TMV in the tumor microenvironment.

PMID- 22479518
TI  - Molecular evolution of the neuropeptide S receptor.
AB  - The neuropeptide S receptor (NPSR) is a recently deorphanized member of the G
      protein-coupled receptor (GPCR) superfamily and is activated by the neuropeptide
      S (NPS). NPSR and NPS are widely expressed in central nervous system and are
      known to have crucial roles in asthma pathogenesis, locomotor activity,
      wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought
      to have first evolved in the tetrapods. Here we examine the origin and the
      molecular evolution of the NPSR using in-silico comparative analyses and document
      the molecular basis of divergence of the NPSR from its closest vertebrate
      paralogs. In this study, NPSR-like sequences have been identified in a
      hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR
      like sequence in the metazoan lineage. Phylogenetic analyses revealed that the
      NPSR is most closely related to the invertebrate cardioacceleratory peptide
      receptor (CCAPR) and the group of vasopressin-like receptors. Gene structure
      features were congruent with the phylogenetic clustering and supported the
      orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific
      analysis between the vertebrate NPSR and the well studied paralogous vasopressin
      like receptor subtypes revealed several putative amino acid sites that may
      account for the observed functional divergence between them. The data can
      facilitate experimental studies aiming at deciphering the common features as well
      as those related to ligand binding and signal transduction processes specific to
      the NPSR.

PMID- 22479519
TI  - Selective regulation of NR2B by protein phosphatase-1 for the control of the NMDA
      receptor in neuroprotection.
AB  - An imbalance between pro-survival and pro-death pathways in brain cells can lead
      to neuronal cell death and neurodegeneration. While such imbalance is known to be
      associated with alterations in glutamatergic and Ca(2+) signaling, the underlying
      mechanisms remain undefined. We identified the protein Ser/Thr phosphatase
      protein phosphatase-1 (PP1), an enzyme associated with glutamate receptors, as a
      key trigger of survival pathways that can prevent neuronal death and
      neurodegeneration in the adult hippocampus. We show that PP1alpha overexpression
      in hippocampal neurons limits NMDA receptor overactivation and Ca(2+) overload
      during an excitotoxic event, while PP1 inhibition favors Ca(2+) overload and cell
      death. The protective effect of PP1 is associated with a selective
      dephosphorylation on a residue phosphorylated by CaMKIIalpha on the NMDA receptor
      subunit NR2B, which promotes pro-survival pathways and associated transcriptional
      programs. These results reveal a novel contributor to the mechanisms of
      neuroprotection and underscore the importance of PP1-dependent dephosphorylation
      in these mechanisms. They provide a new target for the development of potential
      therapeutic treatment of neurodegeneration.

PMID- 22479520
TI  - Disrupted-in-schizophrenia (DISC1) functions presynaptically at glutamatergic
      synapses.
AB  - The pathophysiology of schizophrenia is believed to involve defects in synaptic
      transmission, and the function of many schizophrenia-associated genes, including
      DISC1, have been linked to synaptic function at glutamatergic synapses. Here we
      develop a rodent model via in utero electroporation to assay the presynaptic
      function of DISC1 at glutamatergic synapses. We used a combination of mosaic
      transgene expression, RNAi knockdown and optogenetics to restrict both genetic
      manipulation and synaptic stimulation of glutamatergic neurons presynaptic to
      other layer 2/3 neocortical pyramidal neurons that were then targeted for whole
      cell patch-clamp recording. We show that expression of the DISC1 c-terminal
      truncation variant that is associated with Schizophrenia alters the frequency of
      mEPSCs and the kinetics of evoked glutamate release. In addition, we show that
      expression level of DISC1 is correlated with the probability of glutamate release
      such that increased DISC1 expression results in paired-pulse depression and RNAi
      knockdown of DISC1 produces paired-pulse facilitation. Overall, our results
      support a direct presynaptic function for the schizophrenia-associated gene,
      DISC1.

PMID- 22479521
TI  - RNA sensors enable human mast cell anti-viral chemokine production and IFN
      mediated protection in response to antibody-enhanced dengue virus infection.
AB  - Dengue hemorrhagic fever and/or dengue shock syndrome represent the most serious
      pathophysiological manifestations of human dengue virus infection. Despite
      intensive research, the mechanisms and important cellular players that contribute
      to dengue disease are unclear. Mast cells are tissue-resident innate immune cells
      that play a sentinel cell role in host protection against infectious agents via
      pathogen-recognition receptors by producing potent mediators that modulate
      inflammation, cell recruitment and normal vascular homeostasis. Most importantly,
      mast cells are susceptible to antibody-enhanced dengue virus infection and
      respond with selective cytokine and chemokine responses. In order to obtain a
      global view of dengue virus-induced gene regulation in mast cells, primary human
      cord blood-derived mast cells (CBMCs) and the KU812 and HMC-1 mast cell lines
      were infected with dengue virus in the presence of dengue-immune sera and their
      responses were evaluated at the mRNA and protein levels. Mast cells responded to
      antibody-enhanced dengue virus infection or polyinosinicpolycytidylic acid
      treatment with the production of type I interferons and the rapid and potent
      production of chemokines including CCL4, CCL5 and CXCL10. Multiple interferon
      stimulated genes were also upregulated as well as mRNA and protein for the RNA
      sensors PKR, RIG-I and MDA5. Dengue virus-induced chemokine production by KU812
      cells was significantly modulated by siRNA knockdown of RIG-I and PKR, in a
      negative and positive manner, respectively. Pretreatment of fresh KU812 cells
      with supernatants from dengue virus-infected mast cells provided protection from
      subsequent infection with dengue virus in a type I interferon-dependent manner.
      These findings support a role for tissue-resident mast cells in the early
      detection of antibody-enhanced dengue virus infection via RNA sensors, the
      protection of neighbouring cells through interferon production and the potential
      recruitment of leukocytes via chemokine production.

PMID- 22479522
TI  - Molecular dynamics analysis of apolipoprotein-D-lipid hydroperoxide interactions:
      mechanism for selective oxidation of Met-93.
AB  - BACKGROUND: Recent studies suggest reduction of radical-propagating fatty acid
      hydroperoxides to inert hydroxides by interaction with apolipoprotein-D (apoD)
      Met93 may represent an antioxidant function for apoD. The nature and structural
      consequences of this selective interaction are unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: Herein we used molecular dynamics (MD) analysis to address these
      issues. Long-timescale simulations of apoD suggest lipid molecules are bound
      flexibly, with the molecules free to explore multiple conformations in a binding
      site at the entrance to the classical lipocalin ligand-binding pocket. Models of
      5s- 12s- and 15s-hydroperoxyeicosatetraenoic acids were created and the lipids
      found to wrap around Met93 thus providing a plausible mechanism by which
      eicosatetraenoic acids bearing hydroperoxides on different carbon atoms can
      interact with Met93 to yield Met93 sulfoxide (Met93SO). Simulations of
      glycosylated apoD indicated that a second solvent exposed Met at position 49 was
      shielded by a triantennerary N-glycan attached to Asn45 thereby precluding lipid
      interactions. MD simulations of apoD showed B-factors of the loop containing
      Met93SO were higher in the oxidized protein, indicating increased flexibility
      that is predicted to destabilize the protein and promote self-association.
      CONCLUSIONS/SIGNIFICANCE: These studies provide novel insights into the
      mechanisms that may contribute to the antioxidant function of apoD and the
      structural consequences that result if Met93SO is not redox-cycled back to its
      native state.

PMID- 22479523
TI  - The natural product domain seeker NaPDoS: a phylogeny based bioinformatic tool to
      classify secondary metabolite gene diversity.
AB  - New bioinformatic tools are needed to analyze the growing volume of DNA sequence
      data. This is especially true in the case of secondary metabolite biosynthesis,
      where the highly repetitive nature of the associated genes creates major
      challenges for accurate sequence assembly and analysis. Here we introduce the web
      tool Natural Product Domain Seeker (NaPDoS), which provides an automated method
      to assess the secondary metabolite biosynthetic gene diversity and novelty of
      strains or environments. NaPDoS analyses are based on the phylogenetic
      relationships of sequence tags derived from polyketide synthase (PKS) and non
      ribosomal peptide synthetase (NRPS) genes, respectively. The sequence tags
      correspond to PKS-derived ketosynthase domains and NRPS-derived condensation
      domains and are compared to an internal database of experimentally characterized
      biosynthetic genes. NaPDoS provides a rapid mechanism to extract and classify
      ketosynthase and condensation domains from PCR products, genomes, and metagenomic
      datasets. Close database matches provide a mechanism to infer the generalized
      structures of secondary metabolites while new phylogenetic lineages provide
      targets for the discovery of new enzyme architectures or mechanisms of secondary
      metabolite assembly. Here we outline the main features of NaPDoS and test it on
      four draft genome sequences and two metagenomic datasets. The results provide a
      rapid method to assess secondary metabolite biosynthetic gene diversity and
      richness in organisms or environments and a mechanism to identify genes that may
      be associated with uncharacterized biochemistry.

PMID- 22479524
TI  - When the transmission of culture is child's play.
AB  - BACKGROUND: Humans frequently engage in arbitrary, conventional behavior whose
      primary purpose is to identify with cultural in-groups. The propensity for doing
      so is established early in human ontogeny as children become progressively
      enmeshed in their own cultural milieu. This is exemplified by their habitual
      replication of causally redundant actions shown to them by adults. Yet children
      seemingly ignore such actions shown to them by peers. How then does culture get
      transmitted intra-generationally? Here we suggest the answer might be 'in play'.
      PRINCIPAL FINDINGS: Using a diffusion chain design preschoolers first watched an
      adult retrieve a toy from a novel apparatus using a series of actions, some of
      which were obviously redundant. These children could then show another child how
      to open the apparatus, who in turn could show a third child. When the adult
      modeled the actions in a playful manner they were retained down to the third
      child at higher rates than when the adult seeded them in a functionally oriented
      way. CONCLUSIONS: Our results draw attention to the possibility that play might
      serve a critical function in the transmission of human culture by providing a
      mechanism for arbitrary ideas to spread between children.

PMID- 22479526
TI  - Effects of seawater acidification on cell cycle control mechanisms in
      Strongylocentrotus purpuratus embryos.
AB  - Previous studies have shown fertilization and development of marine species can
      be significantly inhibited when the pH of sea water is artificially lowered.
      Little mechanistic understanding of these effects exists to date, but previous
      work has linked developmental inhibition to reduced cleavage rates in embryos. To
      explore this further, we tested whether common cell cycle checkpoints were
      involved using three cellular biomarkers of cell cycle progression: (1) the onset
      of DNA synthesis, (2) production of a mitotic regulator, cyclin B, and (3)
      formation of the mitotic spindle. We grew embryos of the purple sea urchin,
      Strongylocentrotus purpuratus, in seawater artifically buffered to a pH of ~7.0,
      7.5, and 8.0 by CO(2) infusion. Our results suggest the reduced rates of mitotic
      cleavage are likely unrelated to common cell cycle checkpoints. We found no
      significant differences in the three biomarkers assessed between pH treatments,
      indicating the embryos progress through the G(1)/S, G(2)/M and metaphase/anaphase
      transitions at relatively similar rates. These data suggest low pH environments
      may not impact developmental programs directly, but may act through secondary
      mechanisms such as cellular energetics.

PMID- 22479525
TI  - The regulatory repertoire of Pseudomonas aeruginosa AmpC beta-lactamase regulator
      AmpR includes virulence genes.
AB  - In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR
      family, regulates the expression of a chromosomal beta-lactamase AmpC. The
      regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an
      opportunistic pathogen responsible for numerous acute and chronic infections
      including cystic fibrosis. In addition to regulating ampC, P. aeruginosa AmpR
      regulates the sigma factor AlgT/U and production of some quorum sensing (QS)
      regulated virulence factors. In order to better understand the ampR regulon, we
      compared the transcriptional profile generated using DNA microarrays of the
      prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant,
      PAODeltaampR. Transcriptome analysis demonstrates that the AmpR regulon is much
      more extensive than previously thought, with the deletion of ampR influencing the
      differential expression of over 500 genes. In addition to regulating resistance
      to beta-lactam antibiotics via AmpC, AmpR also regulates non-beta-lactam
      antibiotic resistance by modulating the MexEF-OprN efflux pump. Other virulence
      mechanisms including biofilm formation and QS-regulated acute virulence factors
      are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the microarray
      data. Further, using a Caenorhabditis elegans model, we demonstrate that a
      functional AmpR is required for P. aeruginosa pathogenicity. AmpR, a member of
      the core genome, also regulates genes in the regions of genome plasticity that
      are acquired by horizontal gene transfer. Further, we show differential
      regulation of other transcriptional regulators and sigma factors by AmpR,
      accounting for the extensive AmpR regulon. The data demonstrates that AmpR
      functions as a global regulator in P. aeruginosa and is a positive regulator of
      acute virulence while negatively regulating biofilm formation, a chronic
      infection phenotype. Unraveling this complex regulatory circuit will provide a
      better understanding of the bacterial response to antibiotics and how the
      organism coordinately regulates a myriad of virulence factors in response to
      antibiotic exposure.

PMID- 22479527
TI  - EGF-induced EMT and invasiveness in serous borderline ovarian tumor cells: a
      possible step in the transition to low-grade serous carcinoma cells?
AB  - In high-grade ovarian cancer cultures, it has been shown that epidermal growth
      factor (EGF) induces cell invasion by activating an epithelial-mesenchymal
      transition (EMT). However, the effect of EGF on serous borderline ovarian tumors
      (SBOT) and low-grade serous carcinomas (LGC) cell invasion remains unknown. Here,
      we show that EGF receptor (EGFR) was expressed, that EGF treatment increased cell
      migration and invasion in two cultured SBOT cell lines, SBOT3.1 and SV40 large T
      antigen-infected SBOT cells (SBOT4-LT), and in two cultured LGC cell lines, MPSC1
      and SV40 LT/ST-immortalized LGC cells (ILGC). However, EGF induced down
      regulation of E-cadherin and concurrent up-regulation of N-cadherin in SBOT cells
      but not in LGC cells. In SBOT cells, the expression of the transcriptional
      repressors of E-cadherin, Snail, Slug and ZEB1 were increased by EGF treatment.
      Treatment with EGF led to the activation of the downstream ERK1/2 and PI3K/Akt.
      The MEK1 inhibitor PD98059 diminished the EGF-induced cadherin switch and the up
      regulation of Snail, Slug and ZEB1 and the EGF-mediated increase in SBOT cell
      migration and invasion. The PI3K inhibitor LY294002 had similar effects, but it
      could not block the EGF-induced up-regulation of N-cadherin and ZEB1. This study
      demonstrates that EGF induces SBOT cell migration and invasion by activating EMT,
      which involves the activation of the ERK1/2 and PI3K/Akt pathways and,
      subsequently, Snail, Slug and ZEB1 expression. Moreover, our results suggest that
      there are EMT-independent mechanisms that mediate the EGF-induced LGC cell
      migration and invasion.

PMID- 22479528
TI  - Automation technology and sense of control: a window on human agency.
AB  - Previous studies have shown that the perceived times of voluntary actions and
      their effects are perceived as shifted towards each other, so that the interval
      between action and outcome seems shortened. This has been referred to as
      'intentional binding' (IB). However, the generality of this effect remains
      unclear. Here we demonstrate that Intentional Binding also occurs in complex
      control situations. Using an aircraft supervision task with different autopilot
      settings, our results first indicated a strong relation between measures of IB
      and different levels of system automation. Second, measures of IB were related to
      explicit agency judgement in this applied setting. We discuss the implications
      for the underlying mechanisms, and for sense of agency in automated environments.

PMID- 22479529
TI  - Silencing of renal DNaseI in murine lupus nephritis imposes exposure of large
      chromatin fragments and activation of Toll like receptors and the Clec4e.
AB  - Recent studies demonstrate that transformation of mild lupus nephritis into end
      stage disease is imposed by silencing of renal DNaseI gene expression in
      (NZBxNZW)F1 mice. Down-regulation of DNaseI results in reduced chromatin
      fragmentation, and in deposition of extracellular chromatin-IgG complexes in
      glomerular basement membranes in individuals that produce IgG anti-chromatin
      antibodies. The main focus of the present study is to describe the biological
      consequences of renal DNaseI shut-down and reduced chromatin fragmentation with a
      particular focus on whether exposed large chromatin fragments activate Toll like
      receptors and the necrosis-related Clec4e receptor in murine and human lupus
      nephritis. Furthermore, analyses where performed to determine if matrix
      metalloproteases are up-regulated as a consequence of chromatin-mediated Toll
      like receptors/Clec4e stimulation. Mouse and human mRNA expression levels of
      DNaseI, Toll like receptors 7-9, Clec4e, pro-inflammatory cytokines and MMP2/MMP9
      were determined and compared with in situ protein expression profiles and
      clinical data. We demonstrate that exposure of chromatin significantly up
      regulate Toll like receptors and Clec4e in mice, and also but less pronounced in
      patients with lupus nephritis treated with immunosuppresants. In conclusion,
      silencing of renal DNaseI gene expression initiates a cascade of inflammatory
      signals leading to progression of both murine and human lupus nephritis.
      Principal component analyses biplot of data from murine and human lupus nephrits
      demonstrate the importance of DNaseI gene shut down for progression of the organ
      disease.

PMID- 22479530
TI  - Increased fibrosis and interstitial fluid pressure in two different types of
      syngeneic murine carcinoma grown in integrin beta3-subunit deficient mice.
AB  - Stroma properties affect carcinoma physiology and direct malignant cell
      development. Here we present data showing that alpha(V)beta(3) expressed by
      stromal cells is involved in the control of interstitial fluid pressure (IFP),
      extracellular volume (ECV) and collagen scaffold architecture in experimental
      murine carcinoma. IFP was elevated and ECV lowered in syngeneic CT26 colon and
      LM3 mammary carcinomas grown in integrin beta(3)-deficient compared to wild-type
      BALB/c mice. Integrin beta(3)-deficiency had no effect on carcinoma growth rate
      or on vascular morphology and function. Analyses by electron microscopy of
      carcinomas from integrin beta(3)-deficient mice revealed a coarser and denser
      collagen network compared to carcinomas in wild-type littermates. Collagen fibers
      were built from heterogeneous and thicker collagen fibrils in carcinomas from
      integrin beta(3)-deficient mice. The fibrotic extracellular matrix (ECM) did not
      correlate with increased macrophage infiltration in integrin beta(3)-deficient
      mice bearing CT26 tumors, indicating that the fibrotic phenotype was not mediated
      by increased inflammation. In conclusion, we report that integrin beta(3)
      deficiency in tumor stroma led to an elevated IFP and lowered ECV that correlated
      with a more fibrotic ECM, underlining the role of the collagen network for
      carcinoma physiology.

PMID- 22479531
TI  - School absenteeism as an adjunct surveillance indicator: experience during the
      second wave of the 2009 H1N1 pandemic in Quebec, Canada.
AB  - BACKGROUND: A school absenteeism surveillance system was implemented in the
      province of Quebec, Canada during the second wave of the 2009 H1N1 pandemic. This
      paper compares this surveillance approach with other available indicators.
      METHOD: All (3432) elementary and high schools from Quebec were included. Each
      school was required to report through a web-based system any day where the
      proportion of students absent for influenza-like illness (ILI) exceeded 10% of
      current school enrolment. RESULTS: Between October 18 and December 12 2009, 35.6%
      of all schools met the 10% absenteeism threshold. This proportion was greater in
      elementary compared to high schools (40% vs 19%) and in smaller compared to
      larger schools (44% vs 22%). The maximum absenteeism rate was reached the first
      day of reporting or within the next two days in 55% and 31% of schools
      respectively. The first reports and subsequent peak in school absenteeism
      provincially preceded the peak in paediatric hospitalization by two and one
      weeks, respectively. Trends in school surveillance otherwise mirrored other
      indicators. CONCLUSION: During a pandemic, school outbreak surveillance based on
      a 10% threshold appears insufficient to trigger timely intervention within a
      given affected school. However, school surveillance appears well-correlated and
      slightly anticipatory compared to other population indicators. As such, school
      absenteeism warrants further evaluation as an adjunct surveillance indicator
      whose overall utility will depend upon specified objectives, and other existing
      capacity for monitoring and response.

PMID- 22479533
TI  - The relationship between phytoplankton distribution and water column
      characteristics in North West European shelf sea waters.
AB  - Phytoplankton underpin the marine food web in shelf seas, with some species
      having properties that are harmful to human health and coastal aquaculture.
      Pressures such as climate change and anthropogenic nutrient input are
      hypothesized to influence phytoplankton community composition and distribution.
      Yet the primary environmental drivers in shelf seas are poorly understood. To
      begin to address this in North Western European waters, the phytoplankton
      community composition was assessed in light of measured physical and chemical
      drivers during the "Ellett Line" cruise of autumn 2001 across the Scottish
      Continental shelf and into adjacent open Atlantic waters. Spatial variability
      existed in both phytoplankton and environmental conditions, with clear
      differences not only between on and off shelf stations but also between different
      on shelf locations. Temperature/salinity plots demonstrated different water
      masses existed in the region. In turn, principal component analysis (PCA), of the
      measured environmental conditions (temperature, salinity, water density and
      inorganic nutrient concentrations) clearly discriminated between shelf and
      oceanic stations on the basis of DIN:DSi ratio that was correlated with both
      salinity and temperature. Discrimination between shelf stations was also related
      to this ratio, but also the concentration of DIN and DSi. The phytoplankton
      community was diatom dominated, with multidimensional scaling (MDS) demonstrating
      spatial variability in its composition. Redundancy analysis (RDA) was used to
      investigate the link between environment and the phytoplankton community. This
      demonstrated a significant relationship between community composition and water
      mass as indexed by salinity (whole community), and both salinity and DIN:DSi
      (diatoms alone). Diatoms of the Pseudo-nitzschia seriata group occurred at
      densities potentially harmful to shellfish aquaculture, with the potential for
      toxicity being elevated by the likelihood of DSi limitation of growth at most
      stations and depths.

PMID- 22479532
TI  - Deciduous trees and the application of universal DNA barcodes: a case study on
      the circumpolar Fraxinus.
AB  - The utility of DNA barcoding for identifying representative specimens of the
      circumpolar tree genus Fraxinus (56 species) was investigated. We examined the
      genetic variability of several loci suggested in chloroplast DNA barcode
      protocols such as matK, rpoB, rpoC1 and trnH-psbA in a large worldwide sample of
      Fraxinus species. The chloroplast intergenic spacer rpl32-trnL was further
      assessed in search for a potentially variable and useful locus. The results of
      the study suggest that the proposed cpDNA loci, alone or in combination, cannot
      fully discriminate among species because of the generally low rates of
      substitution in the chloroplast genome of Fraxinus. The intergenic spacer trnH
      psbA was the best performing locus, but genetic distance-based discrimination was
      moderately successful and only resulted in the separation of the samples at the
      subgenus level. Use of the BLAST approach was better than the neighbor-joining
      tree reconstruction method with pairwise Kimura's two-parameter rates of
      substitution, but allowed for the correct identification of only less than half
      of the species sampled. Such rates are substantially lower than the success rate
      required for a standardised barcoding approach. Consequently, the current cpDNA
      barcodes are inadequate to fully discriminate Fraxinus species. Given that a low
      rate of substitution is common among the plastid genomes of trees, the use of the
      plant cpDNA "universal" barcode may not be suitable for the safe identification
      of tree species below a generic or sectional level. Supplementary barcoding loci
      of the nuclear genome and alternative solutions are proposed and discussed.

PMID- 22479534
TI  - Towards eliminating bias in cluster analysis of TB genotyped data.
AB  - The relative contributions of transmission and reactivation of latent infection
      to TB cases observed clinically has been reported in many situations, but always
      with some uncertainty. Genotyped data from TB organisms obtained from patients
      have been used as the basis for heuristic distinctions between circulating
      (clustered strains) and reactivated infections (unclustered strains). Naive
      methods previously applied to the analysis of such data are known to provide
      biased estimates of the proportion of unclustered cases. The hypergeometric
      distribution, which generates probabilities of observing clusters of a given size
      as realized clusters of all possible sizes, is analyzed in this paper to yield a
      formal estimator for genotype cluster sizes. Subtle aspects of numerical
      stability, bias, and variance are explored. This formal estimator is seen to be
      stable with respect to the epidemiologically interesting properties of the
      cluster size distribution (the number of clusters and the number of singletons)
      though it does not yield satisfactory estimates of the number of clusters of
      larger sizes. The problem that even complete coverage of genotyping, in a
      practical sampling frame, will only provide a partial view of the actual
      transmission network remains to be explored.

PMID- 22479535
TI  - Expression of pluripotency master regulators during two key developmental
      transitions: EGA and early lineage specification in the bovine embryo.
AB  - Pluripotency genes are implicated in mouse embryonic genome activation (EGA) and
      pluripotent lineage specification. Moreover, their expression levels have been
      correlated with embryonic term development. In bovine, however, little
      information is available about dynamics of pluripotency genes during these
      processes. In this study, we charted quantitative and/or qualitative spatio
      temporal expression patterns of transcripts and proteins of pluripotency genes
      (OCT4, SOX2 and NANOG) and mRNA levels of some of their downstream targets in
      bovine oocytes and early embryos. Furthermore, to correlate expression patterns
      of these genes with term developmental potential, we used cloned embryos, having
      similar in vitro but different full term development rates. Our findings affirm:
      firstly, the core triad of pluripotency genes is probably not implicated in
      bovine EGA since their proteins were not detected during pre-EGA phase, despite
      the transcripts for OCT4 and SOX2 were present. Secondly, an earlier ICM
      specification of transcripts and proteins of SOX2 and NANOG makes them pertinent
      candidates of bovine pluripotent lineage specification than OCT4. Thirdly,
      embryos with low term development potential have higher transcription rates;
      nevertheless, precarious balance between pluripotency genes is maintained. This
      balance presages normal in vitro development but, probably higher transcription
      rate disturbs it at later stage that abrogates term development.

PMID- 22479536
TI  - Activation of protein kinase A and exchange protein directly activated by cAMP
      promotes adipocyte differentiation of human mesenchymal stem cells.
AB  - Human mesenchymal stem cells are primary multipotent cells capable of
      differentiating into several cell types including adipocytes when cultured under
      defined in vitro conditions. In the present study we investigated the role of
      cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange
      protein directly activated by cAMP (Epac) in adipocyte conversion of human
      mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP
      signaling involving the simultaneous activation of both PKA- and Epac-dependent
      signaling is critical for this process even in the presence of the strong
      adipogenic inducers insulin, dexamethasone, and rosiglitazone, thereby clearly
      distinguishing the hMADS cells from murine preadipocytes cell lines, where
      rosiglitazone together with dexamethasone and insulin strongly promotes adipocyte
      differentiation. We further show that prostaglandin I(2) (PGI(2)) may fully
      substitute for the cAMP-elevating agent isobutylmethylxanthine (IBMX). Moreover,
      selective activation of Epac-dependent signaling promoted adipocyte
      differentiation when the Rho-associated kinase (ROCK) was inhibited. Unlike the
      case for murine preadipocytes cell lines, long-chain fatty acids, like
      arachidonic acid, did not promote adipocyte differentiation of hMADS cells in the
      absence of a PPARgamma agonist. However, prolonged treatment with the synthetic
      PPARdelta agonist L165041 promoted adipocyte differentiation of hMADS cells in
      the presence of IBMX. Taken together our results emphasize the need for cAMP
      signaling in concert with treatment with a PPARgamma or PPARdelta agonist to
      secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells.

PMID- 22479537
TI  - The chromatin remodeling factor SMARCB1 forms a complex with human
      cytomegalovirus proteins UL114 and UL44.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) uracil DNA glycosylase, UL114, is
      required for efficient viral DNA replication. Presumably, UL114 functions as a
      structural partner to other factors of the DNA-replication machinery and not as a
      DNA repair protein. UL114 binds UL44 (HCMV processivity factor) and UL54 (HCMV
      DNA-polymerase). In the present study we have searched for cellular partners of
      UL114. METHODOLOGY/PRINCIPAL FINDINGS: In a yeast two-hybrid screen SMARCB1, a
      factor of the SWI/SNF chromatin remodeling complex, was found to be an
      interacting partner of UL114. This interaction was confirmed in vitro by co
      immunoprecipitation and pull-down. Immunofluorescence microscopy revealed that
      SMARCB1 along with BRG-1, BAF170 and BAF155, which are the core SWI/SNF
      components required for efficient chromatin remodeling, were present in virus
      replication foci 24-48 hours post infection (hpi). Furthermore a direct
      interaction was also demonstrated for SMARCB1 and UL44. CONCLUSIONS/SIGNIFICANCE:
      The core SWI/SNF factors required for efficient chromatin remodeling are present
      in the HCMV replication foci throughout infection. The proteins UL44 and UL114
      interact with SMARCB1 and may participate in the recruitment of the SWI/SNF
      complex to the chromatinized virus DNA. Thus, the presence of the SWI/SNF
      chromatin remodeling complex in replication foci and its association with UL114
      and with UL44 might imply its involvement in different DNA transactions.

PMID- 22479538
TI  - Early developmental responses to seedling environment modulate later plasticity
      to light spectral quality.
AB  - Correlations between developmentally plastic traits may constrain the joint
      evolution of traits. In plants, both seedling de-etiolation and shade avoidance
      elongation responses to crowding and foliage shade are mediated by partially
      overlapping developmental pathways, suggesting the possibility of pleiotropic
      constraints. To test for such constraints, we exposed inbred lines of Impatiens
      capensis to factorial combinations of leaf litter (which affects de-etiolation)
      and simulated foliage shade (which affects phytochrome-mediated shade avoidance).
      Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced
      subsequent elongation of the first internode in response to low red:far red
      (R:FR). Trait expression was correlated across litter and shade conditions,
      suggesting that phenotypic effects of early plasticity on later plasticity may
      affect variation in elongation traits available to selection in different light
      environments.

PMID- 22479539
TI  - Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting
      LPS-induced iNOS and COX-2 expression via the NF-kappaB inactivation.
AB  - BACKGROUND AND PURPOSE: The edible blue pigments produced by gardenia fruits have
      been used as value-added colorants for foods in East Asia for 20 years. However,
      the biological activity of the blue pigments derived from genipin has not been
      reported. METHODOLOGY/PRINCIPAL FINDINGS: The anti-inflammatory effect of blue
      pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage
      in vitro. The secretions of nitric oxide (NO) and prostaglandin E(2) (PGE(2))
      were inhibited in concentration-dependent manner by blue pigments. Real-time
      reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses
      demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha
      (TNF-alpha) was inhibited, moreover, ELISA results showed that the productions of
      IL-6 and TNF-alpha were inhibited. Cell-based ELISA revealed the COX-2 protein
      expression was inhibited. The proteome profiler array showed that 12 cytokines
      and chemokines involved in the inflammatory process were down-regulated by blue
      pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF
      kappaB) activation induced by LPS, and this was associated with decreasing the
      DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the
      degradation of inhibitor of kappaB (IkappaB) alpha, Inhibitor of NF-kappaB Kinase
      (IKK) alpha, IKK-beta, and phosphorylation of IkappaB-alpha. The anti
      inflammatory effect of blue pigments in vivo was studied in carrageenan-induced
      paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly
      inhibited paw swelling and reduced plasma TNF-alpha and IL-6 production in vivo.
      CONCLUSIONS AND IMPLICATIONS: These results suggest that the anti-inflammatory
      properties of blue pigments might be the results from the inhibition of iNOS, COX
      2, IL-6, IL-1beta, and TNF-alpha expression through the down-regulation of NF
      kappaB activation, which will provide strong scientific evidence for the edible
      blue pigments to be developed as a new health-enhancing nutritional food for the
      prevention and treatment of inflammatory diseases.

PMID- 22479540
TI  - Temporal patterns of nucleotide misincorporations and DNA fragmentation in
      ancient DNA.
AB  - DNA that survives in museum specimens, bones and other tissues recovered by
      archaeologists is invariably fragmented and chemically modified. The extent to
      which such modifications accumulate over time is largely unknown but could
      potentially be used to differentiate between endogenous old DNA and present-day
      DNA contaminating specimens and experiments. Here we examine mitochondrial DNA
      sequences from tissue remains that vary in age between 18 and 60,000 years with
      respect to three molecular features: fragment length, base composition at strand
      breaks, and apparent C to T substitutions. We find that fragment length does not
      decrease consistently over time and that strand breaks occur preferentially
      before purine residues by what may be at least two different molecular mechanisms
      that are not yet understood. In contrast, the frequency of apparent C to T
      substitutions towards the 5'-ends of molecules tends to increase over time. These
      nucleotide misincorporations are thus a useful tool to distinguish recent from
      ancient DNA sources in specimens that have not been subjected to unusual or harsh
      treatments.

PMID- 22479541
TI  - Solar radiation and tidal exposure as environmental drivers of Enhalus acoroides
      dominated seagrass meadows.
AB  - There is strong evidence of a global long-term decline in seagrass meadows that
      is widely attributed to anthropogenic activity. Yet in many regions, attributing
      these changes to actual activities is difficult, as there exists limited
      understanding of the natural processes that can influence these valuable
      ecosystem service providers. Being able to separate natural from anthropogenic
      causes of seagrass change is important for developing strategies that effectively
      mitigate and manage anthropogenic impacts on seagrass, and promote coastal
      ecosystems resilient to future environmental change. The present study
      investigated the influence of environmental and climate related factors on
      seagrass biomass in a large ~250 ha meadow in tropical north east Australia.
      Annual monitoring of the intertidal Enhalus acoroides (L.f.) Royle seagrass
      meadow over eleven years revealed a declining trend in above-ground biomass (54%
      significant overall reduction from 2000 to 2010). Partial Least Squares
      Regression found this reduction to be significantly and negatively correlated
      with tidal exposure, and significantly and negatively correlated with the amount
      of solar radiation. This study documents how natural long-term tidal variability
      can influence long-term seagrass dynamics. Exposure to desiccation, high UV, and
      daytime temperature regimes are discussed as the likely mechanisms for the action
      of these factors in causing this decline. The results emphasise the importance of
      understanding and assessing natural environmentally-driven change when
      interpreting the results of seagrass monitoring programs.

PMID- 22479543
TI  - Syringeal specialization of frequency control during song production in the
      Bengalese finch (Lonchura striata domestica).
AB  - BACKGROUND: Singing in songbirds is a complex, learned behavior which shares many
      parallels with human speech. The avian vocal organ (syrinx) has two potential
      sound sources, and each sound generator is under unilateral, ipsilateral neural
      control. Different songbird species vary in their use of bilateral or unilateral
      phonation (lateralized sound production) and rapid switching between left and
      right sound generation (interhemispheric switching of motor control). Bengalese
      finches (Lonchura striata domestica) have received considerable attention,
      because they rapidly modify their song in response to manipulations of auditory
      feedback. However, how the left and right sides of the syrinx contribute to
      acoustic control of song has not been studied. METHODOLOGY: Three manipulations
      of lateralized syringeal control of sound production were conducted. First,
      unilateral syringeal muscular control was eliminated by resection of the left or
      right tracheosyringeal portion of the hypoglossal nerve, which provides
      neuromuscular innervation of the syrinx. Spectral and temporal features of song
      were compared before and after lateralized nerve injury. In a second experiment,
      either the left or right sound source was devoiced to confirm the role of each
      sound generator in the control of acoustic phonology. Third, air pressure was
      recorded before and after unilateral denervation to enable quantification of
      acoustic change within individual syllables following lateralized nerve
      resection. SIGNIFICANCE: These experiments demonstrate that the left sound source
      produces louder, higher frequency, lower entropy sounds, and the right sound
      generator produces lower amplitude, lower frequency, higher entropy sounds. The
      bilateral division of labor is complex and the frequency specialization is the
      opposite pattern observed in most songbirds. Further, there is evidence for rapid
      interhemispheric switching during song production. Lateralized control of song
      production in Bengalese finches may enhance acoustic complexity of song and
      facilitate the rapid modification of sound production following manipulations of
      auditory feedback.

PMID- 22479542
TI  - Characteristics and outcomes of initial virologic suppressors during analytic
      treatment interruption in a therapeutic HIV-1 gag vaccine trial.
AB  - BACKGROUND: In the placebo-controlled trial ACTG A5197, a trend favoring viral
      suppression was seen in the HIV-1-infected subjects who received a recombinant
      Ad5 HIV-1 gag vaccine. OBJECTIVE: To identify individuals with initial viral
      suppression (plasma HIV-1 RNA set point <3.0 log(10) copies/ml) during the
      analytic treatment interruption (ATI) and evaluate the durability and correlates
      of virologic control and characteristics of HIV sequence evolution. METHODS: HIV
      1 gag and pol RNA were amplified and sequenced from plasma obtained during the
      ATI. Immune responses were measured by flow cytometric analysis and intracellular
      cytokine expression assays. Characteristics of those with and without initial
      viral suppression were compared using the Wilcoxon rank sum and Fisher's exact
      tests. RESULTS: Eleven out of 104 participants (10.6%) were classified as initial
      virologic suppressors, nine of whom had received the vaccine. Initial virologic
      suppressors had significantly less CD4+ cell decline by ATI week 16 as compared
      to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04).
      However, of the ten initial virologic suppressors with a pVL at ATI week 49, only
      three maintained pVL <3.0 log(10) copies/ml. HIV-1 Gag-specific CD4+ interferon
      gamma responses were not associated with initial virologic suppression and no
      evidence of vaccine-driven HIV sequence evolution was detected. Participants with
      initial virologic suppression were found to have a lower percentage of CD4+ CTLA
      4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag
      reactive CD4+ TNF-alpha+ cells expressing either CTLA-4 or PD-1. CONCLUSIONS:
      Among individuals participating in a rAd5 therapeutic HIV-1 gag vaccine trial,
      initial viral suppression was found in a subset of patients, but this response
      was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T
      cells and virologic outcome warrants further study in trials of other therapeutic
      vaccines in development. TRIAL REGISTRATION: ClinicalTrials.gov NCT00080106.

PMID- 22479544
TI  - Reduction of EEG theta power and changes in motor activity in rats treated with
      ceftriaxone.
AB  - The glutamate transporter GLT-1 is responsible for the largest proportion of
      total glutamate transport. Recently, it has been demonstrated that ceftriaxone
      (CEF) robustly increases GLT-1 expression. In addition, physiological studies
      have shown that GLT-1 up-regulation strongly affects synaptic plasticity, and
      leads to an impairment of the prepulse inhibition, a simple form of information
      processing, thus suggesting that GLT-1 over-expression may lead to dysfunctions
      of large populations of neurons. To test this possibility, we assessed whether
      CEF affects cortical electrical activity by using chronic electroencephalographic
      (EEG) recordings in male WKY rats. Spectral analysis showed that 8 days of CEF
      treatment resulted in a delayed reduction in EEG theta power (7-9 Hz) in both
      frontal and parietal derivations. This decrease peaked at day 10, i.e., 2 days
      after the end of treatment, and disappeared by day 16. In addition, we found that
      the same CEF treatment increased motor activity, especially when EEG changes are
      more prominent. Taken together, these data indicate that GLT-1 up-regulation, by
      modulating glutamatergic transmission, impairs the activity of widespread neural
      circuits. In addition, the increased motor activity and prepulse inhibition
      alterations previously described suggest that neural circuits involved in
      sensorimotor control are particularly sensitive to GLT-1 up-regulation.

PMID- 22479545
TI  - B cell: T cell interactions occur within hepatic granulomas during experimental
      visceral leishmaniasis.
AB  - Hepatic resistance to Leishmania donovani infection in mice is associated with
      the development of granulomas, in which a variety of lymphoid and non-lymphoid
      populations accumulate. Although previous studies have identified B cells in
      hepatic granulomas and functional studies in B cell-deficient mice have suggested
      a role for B cells in the control of experimental visceral leishmaniasis, little
      is known about the behaviour of B cells in the granuloma microenvironment. Here,
      we first compared the hepatic B cell population in infected mice, where ~60% of B
      cells are located within granulomas, with that of naive mice. In infected mice,
      there was a small increase in mIgM(lo)mIgD(+) mature B2 cells, but no enrichment
      of B cells with regulatory phenotype or function compared to the naive hepatic B
      cell population, as assessed by CD1d and CD5 expression and by IL-10 production.
      Using 2-photon microscopy to quantify the entire intra-granuloma B cell
      population, in conjunction with the adoptive transfer of polyclonal and HEL
      specific BCR-transgenic B cells isolated from L. donovani-infected mice, we
      demonstrated that B cells accumulate in granulomas over time in an antigen
      independent manner. Intra-vital dynamic imaging was used to demonstrate that
      within the polyclonal B cell population obtained from L. donovani-infected mice,
      the frequency of B cells that made multiple long contacts with endogenous T cells
      was greater than that observed using HEL-specific B cells obtained from the same
      inflammatory environment. These data indicate, therefore, that a subset of this
      polyclonal B cell population is capable of making cognate interactions with T
      cells within this unique environment, and provide the first insights into the
      dynamics of B cells within an inflammatory site.

PMID- 22479546
TI  - Efficient iPS cell production with the MyoD transactivation domain in serum-free
      culture.
AB  - A major difficulty of producing induced pluripotent stem cells (iPSCs) has been
      the low efficiency of reprogramming differentiated cells into pluripotent cells.
      We previously showed that 5% of mouse embryonic fibroblasts (MEFs) were
      reprogrammed into iPSCs when they were transduced with a fusion gene composed of
      Oct4 and the transactivation domain of MyoD (called M(3)O), along with Sox2, Klf4
      and c-Myc (SKM). In addition, M(3)O facilitated chromatin remodeling of
      pluripotency genes in the majority of transduced MEFs, including cells that did
      not become iPSCs. These observations suggested the possibility that more than 5%
      of cells had acquired the ability to become iPSCs given more favorable culture
      conditions. Here, we raised the efficiency of making mouse iPSCs with M(3)O-SKM
      to 26% by culturing transduced cells at low density in serum-free culture medium.
      In contrast, the efficiency increased from 0.1% to only 2% with the combination
      of wild-type Oct4 and SKM (OSKM) under the same culture condition. For human
      iPSCs, M(3)O-SKM achieved 7% efficiency under a similar serum-free culture
      condition, in comparison to 1% efficiency with OSKM. This study highlights the
      power of combining the transactivation domain of MyoD with a favorable culture
      environment.

PMID- 22479547
TI  - Led into temptation? Rewarding brand logos bias the neural encoding of incidental
      economic decisions.
AB  - Human decision-making is driven by subjective values assigned to alternative
      choice options. These valuations are based on reward cues. It is unknown,
      however, whether complex reward cues, such as brand logos, may bias the neural
      encoding of subjective value in unrelated decisions. In this functional magnetic
      resonance imaging (fMRI) study, we subliminally presented brand logos preceding
      intertemporal choices. We demonstrated that priming biased participants'
      preferences towards more immediate rewards in the subsequent temporal discounting
      task. This was associated with modulations of the neural encoding of subjective
      values of choice options in a network of brain regions, including but not
      restricted to medial prefrontal cortex. Our findings demonstrate the general
      susceptibility of the human decision making system to apparently incidental
      contextual information. We conclude that the brain incorporates seemingly
      unrelated value information that modifies decision making outside the decision
      maker's awareness.

PMID- 22479548
TI  - Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral
      treatment cohort in South Africa: comparison with rates in the community.
AB  - BACKGROUND: Although antiretroviral therapy (ART) is known to be associated with
      time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of
      ART on incidence remains imprecisely defined due to limited duration of follow-up
      and incomplete CD4 cell count recovery in existing studies. We determined TB
      incidence in a South African ART cohort with up to 8 years of follow-up and
      stratified rates according to CD4 cell count recovery. We compared these rates
      with those of HIV-uninfected individuals living in the same community.
      METHODOLOGY/PRINCIPAL FINDINGS: Prospectively collected clinical data on patients
      receiving ART in a community-based cohort in Cape Town were analysed. 1544
      patients with a median follow-up of 5.0 years (IQR 2.4-5.8) were included in the
      analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in
      424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate
      during the first year of ART was 12.4 (95% CI 10.8-14.4) cases/100PYs and
      decreased to 4.92 (95% CI 3.64-8.62) cases/100PYs between 5 and 8 years of ART.
      During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301
      400, 401-500, 501-700 and >=700 cells/uL, TB incidence rates (95% CI) were 25.5
      (21.6-30.3), 11.2 (9.4-13.5), 7.9 (6.4-9.7), 5.0 (3.9-6.6), 5.1 (3.8-6.8), 4.1
      (3.1-5.4) and 2.7 (1.7-4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9
      78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load
      measurements were independently associated with long-term TB risk. TB rates
      during person-time accrued in the highest CD4 cell count stratum (>700 cells/uL)
      were 4.4-fold higher that the rate in HIV uninfected individuals living in the
      same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58-0.65).
      CONCLUSIONS/SIGNIFICANCE: TB rates during long-term ART remained substantially
      greater than rates in the local HIV uninfected populations regardless of duration
      of ART or attainment of CD4 cell counts exceeding 700 cells/uL.

PMID- 22479549
TI  - The hydrophobic core of twin-arginine signal sequences orchestrates specific
      binding to Tat-pathway related chaperones.
AB  - Redox enzyme maturation proteins (REMPs) bind pre-proteins destined for
      translocation across the bacterial cytoplasmic membrane via the twin-arginine
      translocation system and enable the enzymatic incorporation of complex cofactors.
      Most REMPs recognize one specific pre-protein. The recognition site usually
      resides in the N-terminal signal sequence. REMP binding protects signal peptides
      against degradation by proteases. REMPs are also believed to prevent binding of
      immature pre-proteins to the translocon. The main aim of this work was to better
      understand the interaction between REMPs and substrate signal sequences. Two
      REMPs were investigated: DmsD (specific for dimethylsulfoxide reductase, DmsA)
      and TorD (specific for trimethylamine N-oxide reductase, TorA). Green fluorescent
      protein (GFP) was genetically fused behind the signal sequences of TorA and DmsA.
      This ensures native behavior of the respective signal sequence and excludes any
      effects mediated by the mature domain of the pre-protein. Surface plasmon
      resonance analysis revealed that these chimeric pre-proteins specifically bind to
      the cognate REMP. Furthermore, the region of the signal sequence that is
      responsible for specific binding to the corresponding REMP was identified by
      creating region-swapped chimeric signal sequences, containing parts of both the
      TorA and DmsA signal sequences. Surprisingly, specificity is not encoded in the
      highly variable positively charged N-terminal region of the signal sequence, but
      in the more similar hydrophobic C-terminal parts. Interestingly, binding of DmsD
      to its model substrate reduced membrane binding of the pre-protein. This property
      could link REMP-signal peptide binding to its reported proofreading function.

PMID- 22479550
TI  - Associations of infant nutrition with insulin resistance measures in early
      adulthood: evidence from the Barry-Caerphilly Growth (BCG) study.
AB  - BACKGROUND: Previous studies suggest that over-nutrition in early infancy may
      programme long-term susceptibility to insulin resistance. OBJECTIVE: To assess
      the association of breast milk and quantity of infant formula and cows' milk
      intake during infancy with insulin resistance measures in early adulthood.
      DESIGN: Long-term follow-up of the Barry Caerphilly Growth cohort, into which
      mothers and their offspring had originally been randomly assigned, between 1972
      1974, to receive milk supplementation or not. Participants were the offspring,
      aged 23-27 years at follow-up (n = 679). Breastfeeding and formula/cows' milk
      intake was recorded prospectively by nurses. The main outcomes were insulin
      sensitivity (ISI(0)) and insulin secretion (CIR(30)). RESULTS: 573 (84%)
      individuals had valid glucose and insulin results and complete covariate
      information. There was little evidence of associations of breastfeeding versus
      any formula/cows' milk feeding or of increasing quartiles of formula/cows' milk
      consumption during infancy (<3 months) with any outcome measure in young
      adulthood. In fully adjusted models, the differences in outcomes between
      breastfeeding versus formula/cows' milk feeding at 3 months were: fasting glucose
      (-0.07 mmol/l; 95% CI: -0.19, 0.05); fasting insulin (8.0%; -8.7, 27.6); ISI(0) (
      6.1%; -11.3, 12.1) and CIR(30) (3.8%; -19.0, 32.8). There was also little
      evidence that increasing intakes of formula/cows' milk at 3 months were
      associated with fasting glucose (increase per quartile of formula/cows' milk
      intake = 0.00 mmol/l; -0.03, 0.03); fasting insulin (0.8%; -3.2, 5.1); ISI (0) (
      0.9%; -5.1, 3.5) and CIR(30) (-2.6%; -8.4, 3.6). CONCLUSIONS: We found no
      evidence that increasing consumption of formula/cows' milk in early infancy was
      associated with insulin resistance in young adulthood.

PMID- 22479551
TI  - Similar or different? The role of the ventrolateral prefrontal cortex in
      similarity detection.
AB  - Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour
      when asked to place a banana and an orange in a single category: some patients
      categorize them at a concrete level (e.g., "both have peel"), while others
      continue to look for differences between these objects (e.g., "one is yellow, the
      other is orange"). These observations raise the question of whether abstraction
      and similarity detection are distinct processes involved in abstract
      categorization, and that depend on separate areas of the prefrontal cortex (PFC).
      We designed an original experimental paradigm for a functional magnetic resonance
      imaging (fMRI) study involving healthy subjects, confirming the existence of two
      distinct processes relying on different prefrontal areas, and thus explaining the
      behavioural dissociation in frontal lesion patients. We showed that: 1)
      Similarity detection involves the anterior ventrolateral PFC bilaterally with a
      right-left asymmetry: the right anterior ventrolateral PFC is only engaged in
      detecting physical similarities; 2) Abstraction per se activates the left
      dorsolateral PFC.

PMID- 22479552
TI  - MicroRNA-141 represses HBV replication by targeting PPARA.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression
      primarily at the post-transcriptional level and play critical roles in a variety
      of physiological and pathological processes. In this report, miR-141 was
      identified to repress HBV expression by screening a small miRNA expressing
      library and synthetic miR-141 mimics could also significantly suppress HBV
      expression and replication in HepG2 cells. Bioinformatic analysis and experiment
      assays indicate that peroxisome proliferator-activated receptor alpha (PPARA) was
      the target of hsa-miR-141 during this process. Furthermore, knockdown of PPARA by
      small interfering RNA (siRNA) inhibited HBV replication similar to levels
      observed for miR-141. Promoter functional analysis indicated that repression of
      HBV replication by miR-141 mimics or siRNA was mediated by interfering with the
      HBV promoter functions, consistent with previous studies demonstrating that PPARA
      regulated HBV gene expression through interactions with HBV promoter regulatory
      elements. Our results suggest that miR-141 suppressed HBV replication by reducing
      HBV promoter activities by down-regulating PPARA. This study provides new
      insights into the molecular mechanisms associated with HBV-host interactions.
      Furthermore, this information may facilitate the development of novel anti-HBV
      therapeutic strategies.

PMID- 22479553
TI  - CRISPR/cas loci of type II Propionibacterium acnes confer immunity against
      acquisition of mobile elements present in type I P. acnes.
AB  - Propionibacterium acnes is a skin commensal that occasionally acts as an
      opportunistic pathogen. The population structure of this species shows three main
      lineages (I-III). While type I strains are mainly associated with sebaceous
      follicles of human skin and inflammatory acne, types II and III strains are more
      often associated with deep tissue infections. We investigated the occurrence and
      distribution of the clustered regularly interspaced short palindromic repeats
      (CRISPR) in P. acnes, assessed their immunological memory, and addressed the
      question if such a system could account for type-specific properties of the
      species. A collection of 108 clinical isolates covering all known phylotypes of
      P. acnes was screened for the existence of CRISPR/cas loci. We found that CRISPR
      loci are restricted to type II P. acnes strains. Sequence analyses of the CRISPR
      spacers revealed that the system confers immunity to P. acnes-specific phages and
      to two mobile genetic elements. These elements are found almost exclusively in
      type I P. acnes strains. Genome sequencing of a type I P. acnes isolate revealed
      that one element, 54 kb in size, encodes a putative secretion/tight adherence
      (TAD) system. Thus, CRISPR/cas loci in P. acnes recorded the exposure of type II
      strains to mobile genetic elements of type I strains. The CRISPR/cas locus is
      deleted in type I strains, which conceivably accounts for their ability to
      horizontally acquire fitness or virulence traits and might indicate that type I
      strains constitute a younger subpopulation of P. acnes.

PMID- 22479555
TI  - Unlike for human monocytes after LPS activation, release of TNF-alpha by THP-1
      cells is produced by a TACE catalytically different from constitutive TACE.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory
      cytokine today identified as a key mediator of several chronic inflammatory
      diseases. TNF-alpha, initially synthesized as a membrane-anchored precursor (pro
      TNF-alpha), is processed by proteolytic cleavage to generate the secreted mature
      form. TNF-alpha converting enzyme (TACE) is currently the first and single
      protease described as responsible for the inducible release of soluble TNF-alpha.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrated the presence on THP-1 cells
      as on human monocytes of a constitutive proteolytical activity able to cleave pro
      TNF-alpha. Revelation of the cell surface TACE protein expression confirmed that
      the observed catalytic activity is due to TACE. However, further studies using
      effective and innovative TNF-alpha inhibitors, as well as a highly selective TACE
      inhibitor, support the presence of a catalytically different sheddase activity on
      LPS activated THP-1 cells. It appears that this catalytically different TACE
      protease activity might have a significant contribution to TNF-alpha release in
      LPS activated THP-1 cells, by contrast to human monocytes where the TACE activity
      remains catalytically unchanged even after LPS activation.
      CONCLUSIONS/SIGNIFICANCE: On the surface of LPS activated THP-1 cells we
      identified a releasing TNF-alpha activity, catalytically different from the
      sheddase activity observed on human monocytes from healthy donors. This
      catalytically-modified TACE activity is different from the constitutive shedding
      activity and appears only upon stimulation by LPS.

PMID- 22479554
TI  - A cell permeable peptide inhibitor of NFAT inhibits macrophage cytokine
      expression and ameliorates experimental colitis.
AB  - Nuclear factor of activated T cells (NFAT) plays a critical role in the
      development and function of immune and non-immune cells. Although NFAT is a
      central transcriptional regulator of T cell cytokines, its role in macrophage
      specific gene expression is less defined. Previous work from our group
      demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we
      further investigate NFAT function in murine macrophages and determined the
      effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental
      colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with
      tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-gamma
      induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were
      also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter
      was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10(
      /-)) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was
      independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was
      administered systemically to Il10(-/-) mice with piroxicam-induced colitis. 11R
      VIVIT treated mice demonstrated significant improvement in colitis compared to
      mice treated with an inactive peptide. Moreover, decreased spontaneous secretion
      of IL-12 p40 and TNF in supernatants from colon explant cultures was
      demonstrated. In summary, NFAT, widely recognized for its role in T cell biology,
      also regulates important innate inflammatory pathways in macrophages. Selective
      blocking of NFAT via a cell permeable inhibitory peptide is a promising
      therapeutic strategy for the treatment of inflammatory bowel diseases.

PMID- 22479557
TI  - Laboratory monitoring of patients treated with antihypertensive drugs and newly
      exposed to non steroidal anti-inflammatory drugs: a cohort study.
AB  - BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs
      (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin
      Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia.
      Thus, monitoring of serum creatinine and potassium is recommended when a first
      dispensing of NSAID occur in patients treated with these drugs. METHODS: We
      conducted a pharmacoepidemiological retrospective cohort study using data from
      the French Health Insurance Reimbursement Database to evaluate the proportion of
      serum creatinine and potassium laboratory monitoring in patients treated with
      ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the
      first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients
      treated with antihypertensive drugs) and analyzed serum creatinine and potassium
      laboratory monitoring within the 3 weeks after the first NSAID dispensing.
      RESULTS: General Practitioners were the most frequent prescribers of NSAIDs
      (85.5%, 95% CI: 84.3-86.6). The more commonly prescribed NSAIDs were ibuprofen
      (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine
      and potassium monitoring was 10.7% (95% CI: 9.5-11.8) in patients treated by
      ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to
      women aged over 60, treated with digoxin or glucose lowering drugs, but not to
      patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when
      NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION:
      Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs
      or diuretics and receiving a first NSAID dispensing is insufficiently performed
      and needs to be reinforced through specific interventions.

PMID- 22479556
TI  - Tuberculosis in HIV-negative and HIV-infected patients in a low-incidence
      country: clinical characteristics and treatment outcomes.
AB  - BACKGROUND: In Switzerland and other developed countries, the number of
      tuberculosis (TB) cases has been decreasing for decades, but HIV-infected
      patients and migrants remain risk groups. The aim of this study was to compare
      characteristics of TB in HIV-negative and HIV-infected patients diagnosed in
      Switzerland, and between coinfected patients enrolled and not enrolled in the
      national Swiss HIV Cohort Study (SHCS). METHODS AND FINDINGS: All patients
      diagnosed with culture-confirmed TB in the SHCS and a random sample of culture
      confirmed cases reported to the national TB registry 2000-2008 were included.
      Outcomes were assessed in HIV-infected patients and considered successful in case
      of cure or treatment completion. Ninety-three SHCS patients and 288 patients
      selected randomly from 4221 registered patients were analyzed. The registry
      sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the
      estimated number of HIV-infected patients not enrolled in the SHCS but reported
      to the registry 2000-2008 was 146 (95% CI 122-173). Coinfected patients were more
      likely to be from sub-Saharan Africa (51.5% versus 15.8%, P<0.0001) and to
      present disseminated disease (23.9% vs. 3.4%, P<0.0001) than HIV-negative
      patients. Coinfected patients not enrolled in the SHCS were asylum seekers or
      migrant workers, with lower CD4 cell counts at TB diagnosis (median CD4 count 79
      cells/uL compared to 149 cells/uL among SHCS patients, P = 0.07). There were 6
      patients (60.0%) with successful outcomes compared to 82 (88.2%) patients in the
      SHCS (P = 0.023). CONCLUSIONS: The clinical presentation of coinfected patients
      differed from HIV-negative TB patients. The number of HIV-infected patients
      diagnosed with TB outside the SHCS is similar to the number diagnosed within the
      cohort but outcomes are poorer in patients not followed up in the national
      cohort. Special efforts are required to address the needs of this vulnerable
      population.

PMID- 22479558
TI  - Effects of sperm conjugation and dissociation on sperm viability in vitro.
AB  - Sperm conjugation is an unusual variation in sperm behavior where two or more
      spermatozoa physically unite for motility or transport through the female
      reproductive tract. Conjugation has frequently been interpreted as sperm
      cooperation, including reproductive altruism, with some sperm advancing their
      siblings toward the site of fertilization while ostensibly forfeiting their own
      ability to fertilize through damage incurred during conjugate break-up.
      Conversely, conjugation has been proposed to protect sensitive regions of
      spermatozoa from spermicidal conditions within the female reproductive tract. We
      investigated the possibility of dissociation-induced sperm mortality and tested
      for a protective function of conjugation using the paired sperm of the diving
      beetle, Graphoderus liberus. Sperm conjugates were mechanically dissociated and
      exposed to potentially damaging tissue extracts of the female reproductive tract
      and somatic tissue. We found no significant difference in viability between
      paired sperm and dissociated, single sperm. The results further indicate that the
      reproductive tract of female G. liberus might not be spermicidal and conjugation
      is not protective of sperm viability when damaging conditions do exist. Our
      results support the interpretation that, at least in some taxa, sperm conjugation
      is neither protective nor damaging to sperm viability.

PMID- 22479559
TI  - Estimating animal abundance in ground beef batches assayed with molecular
      markers.
AB  - Estimating animal abundance in industrial scale batches of ground meat is
      important for mapping meat products through the manufacturing process and for
      effectively tracing the finished product during a food safety recall. The
      processing of ground beef involves a potentially large number of animals from
      diverse sources in a single product batch, which produces a high heterogeneity in
      capture probability. In order to estimate animal abundance through DNA profiling
      of ground beef constituents, two parameter-based statistical models were
      developed for incidence data. Simulations were applied to evaluate the maximum
      likelihood estimate (MLE) of a joint likelihood function from multiple surveys,
      showing superiority in the presence of high capture heterogeneity with small
      sample sizes, or comparable estimation in the presence of low capture
      heterogeneity with a large sample size when compared to other existing models.
      Our model employs the full information on the pattern of the capture-recapture
      frequencies from multiple samples. We applied the proposed models to estimate
      animal abundance in six manufacturing beef batches, genotyped using 30 single
      nucleotide polymorphism (SNP) markers, from a large scale beef grinding facility.
      Results show that between 411~1367 animals were present in six manufacturing beef
      batches. These estimates are informative as a reference for improving recall
      processes and tracing finished meat products back to source.

PMID- 22479560
TI  - Mutations, clinical findings and survival estimates in South American patients
      with X-linked adrenoleukodystrophy.
AB  - In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X
      ALD) patients and relatives from 38 unrelated families from South America, as
      well as phenotypic proportions, survival estimates, and the potential effect of
      geographical origin in clinical characteristics. METHODS: X- ALD patients from
      Brazil, Argentina and Uruguay were invited to participate in molecular studies to
      determine their genetic status, characterize the mutations and improve the
      genetic counseling of their families. All samples were screened by SSCP analysis
      of PCR fragments, followed by automated DNA sequencing to establish the specific
      mutation in each family. Age at onset and at death, male phenotypes, genetic
      status of women, and the effect of family and of latitude of origin were also
      studied. RESULTS: We identified thirty-six different mutations (twelve novel).
      This population had an important allelic heterogeneity, as only p.Arg518Gln was
      repeatedly found (three families). Four cases carried de novo mutations. Intra
      familiar phenotype variability was observed in all families. Out of 87 affected
      males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages
      at onset and at death of the CALD were 10.9 (9.1-12.7) and 24.7 (19.8-29.6)
      years. No association was found between phenotypic manifestations and latitude of
      origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and
      had completely skewed X inactivation. CONCLUSIONS: This study extends the
      spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and
      the absence of common mutations, and suggests a possible high frequency of
      cerebral forms in our population.

PMID- 22479561
TI  - Comparative toxicity of nanoparticulate CuO and ZnO to soil bacterial
      communities.
AB  - The increasing industrial application of metal oxide Engineered Nano-Particles
      (ENPs) is likely to increase their environmental release to soils. While the
      potential of metal oxide ENPs as environmental toxicants has been shown, lack of
      suitable control treatments have compromised the power of many previous
      assessments. We evaluated the ecotoxicity of ENP (nano) forms of Zn and Cu oxides
      in two different soils by measuring their ability to inhibit bacterial growth. We
      could show a direct acute toxicity of nano-CuO acting on soil bacteria while the
      macroparticulate (bulk) form of CuO was not toxic. In comparison, CuSO(4) was
      more toxic than either oxide form. Unlike Cu, all forms of Zn were toxic to soil
      bacteria, and the bulk-ZnO was more toxic than the nano-ZnO. The ZnSO(4) addition
      was not consistently more toxic than the oxide forms. Consistently, we found a
      tight link between the dissolved concentration of metal in solution and the
      inhibition of bacterial growth. The inconsistent toxicological response between
      soils could be explained by different resulting concentrations of metals in soil
      solution. Our findings suggested that the principal mechanism of toxicity was
      dissolution of metal oxides and sulphates into a metal ion form known to be
      highly toxic to bacteria, and not a direct effect of nano-sized particles acting
      on bacteria. We propose that integrated efforts toward directly assessing
      bioavailable metal concentrations are more valuable than spending resources to
      reassess ecotoxicology of ENPs separately from general metal toxicity.

PMID- 22479562
TI  - Association between hepatic steatosis and entecavir treatment failure in Chinese
      patients with chronic hepatitis B.
AB  - BACKGROUND: The coexistence of HBV infection and nonalcoholic fatty liver disease
      (NAFLD) becomes characteristic of liver disease in China, with unknown bilateral
      influence. We aimed to investigate the effect of hepatic steatosis, a common
      hepatocyte change in NAFLD, on antiviral therapy in patients with chronic
      hepatitis B (CHB). METHODS AND FINDINGS: We carried out a prospective nested case
      control study in CHB patients receiving Entecavir for initial antiviral therapy,
      by recording demographic, anthropometric and clinical data at baseline, 24(wk),
      48(wk) and 96(wk). Univariate analysis and multivariate logistic regression were
      applied to find out independent factors of hepatic steatosis and Entecavir
      treatment failure. The rates of HBV-DNA clearance, HBeAg seroconversion and ALT
      normalization were compared between CHB patients with and without steatosis by
      post hoc analysis. A total of 267 Chinese patients with CHB entered final
      analysis, with overall percentages of hepatic steatosis and HBeAg positive as
      30.5% and 62.4%. Multivariate analysis showed waist circumference, serum TG and
      uric acid levels were independent factors of hepatic steatosis. The response
      rates to Entecavir were 54.9%, 63.8%, 74.2% at 24(wk), 48(wk) and 96(wk). Hepatic
      steatosis was revealed as an independent factor of Entecavir treatment failure by
      multivariate logistic regression at 24(wk), 48(wk) and 96(wk). In CHB patients
      with hepatic steatosis, HBV-DNA clearance and HBeAg seroconversion were both
      lower throughout the follow-up, but only the former reached statistical
      significance. Besides, ALT normalization was also significantly lower at 24(wk)
      and 48(wk). CONCLUSION: Hepatic steatosis is significantly associated with
      Entecavir treatment failure and metabolic factors are independent factors of
      hepatic steatosis in CHB patients, which called for a specified antiviral
      strategy in CHB patients with NAFLD.

PMID- 22479563
TI  - C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular
      calcium release and anti-apoptotic activity.
AB  - Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine
      present at the C-terminus of peptides or proteins. CPM is thought to be involved
      in inflammatory processes. This is corroborated by CPM-mediated trimming and
      modulation of inflammatory factors, and expression of the protease in
      inflammatory environments. Since the function of CPM in and beyond inflammation
      remains mainly undefined, the identification of natural substrates can aid in
      discovering the (patho)physiological role of CPM. CCL1/I-309, with its three C
      terminal basic amino acids, forms a potential natural substrate for CPM. CCL1
      plays a role not only in inflammation but also in apoptosis, angiogenesis and
      tumor biology. Enzymatic processing differently impacts the biological activity
      of chemokines thereby contributing to the complex regulation of the chemokine
      system. The aim of the present study was to investigate whether (i) CCL1/I-309 is
      prone to trimming by CPM, and (ii) the biological activity of CCL1 is altered
      after C-terminal proteolytic processing. CCL1 was identified as a novel substrate
      for CPM in vitro using mass spectrometry. C-terminal clipping of CCL1 augmented
      intracellular calcium release mediated by CCR8 but reduced the binding of CCL1 to
      CCR8. In line with the higher intracellular calcium release, a pronounced
      increase of the anti-apoptotic activity of CCL1 was observed in the BW5147
      cellular model. CCR8 signaling, CCR8 binding and anti-apoptotic activity were
      unaffected when CPM was exposed to the carboxypeptidase inhibitor DL-2
      mercaptomethyl-3-guanidino-ethylthiopropanoic acid. The results of this study
      suggest that CPM is a likely candidate for the regulation of biological processes
      relying on the CCL1-CCR8 system.

PMID- 22479564
TI  - Impact of inconsistent policies for transfusion-transmitted malaria on clinical
      practice in Ghana.
AB  - BACKGROUND: Policies concerning the prevention of transfusion transmitted malaria
      (TTM) are the responsibility of blood transfusion services and malaria control
      programmes. To prevent spreading drug resistance due to over-use of malaria
      drugs, recent malaria treatment guidelines recommend prompt parasitological
      confirmation before treatment is started. In contrast, blood safety policies from
      the World Health Organisation (WHO) recommend presumptive malaria treatment for
      recipients of blood in endemic countries but evidence supporting this approach is
      lacking. Our study documented how these conflicting policies relating to malaria
      transmission through blood transfusion impact on clinical practice in a teaching
      hospital in West Africa. METHODS/PRINCIPAL FINDINGS: We randomly selected and
      reviewed case notes of 151 patients within 24 hours of their receiving a blood
      transfusion. Transfusion practices including the confirmation of diagnosis and
      anti-malarial treatment given were compared across three departments; Obstetrics
      and Gynaecology (O&G), Paediatrics and Medicine. Overall, 66 (44%) of patients
      received malaria treatment within 24 hrs of their blood transfusion; of which
      only 2 (3%) received anti-malarials based on a laboratory confirmation of
      malaria. Paediatric patients (87%) received the most anti-malarials and only 7%
      and 24% of recipients in medicine and O&G respectively received anti malarials.
      In 51 patients (78%), the anti-malarials were prescribed at the same time as the
      blood transfusion and anti-malarials prescriptions exceeded the number of
      patients with a presumptive diagnosis of malaria. CONCLUSIONS: It is common
      practice in paediatrics to prescribe anti-malarials routinely with blood
      transfusions. This contravenes the malaria treatment guidelines of laboratory
      confirmation before treatment but is in accordance with the less-well evidenced
      blood safety guidelines. There is an urgent need for more evidence about the
      clinical impact of transfusion transmitted malaria to enable malaria and blood
      transfusion programmes to harmonize their policies and give clear guidance to
      clinicians who prescribe blood transfusions in malaria-endemic areas.

PMID- 22479565
TI  - Circadian timing of injury-induced cell proliferation in zebrafish.
AB  - In certain vertebrates such as the zebrafish, most tissues and organs including
      the heart and central nervous system possess the remarkable ability to regenerate
      following severe injury. Both spatial and temporal control of cell proliferation
      and differentiation is essential for the successful repair and re-growth of
      damaged tissues. Here, using the regenerating adult zebrafish caudal fin as a
      model, we have demonstrated an involvement of the circadian clock in timing cell
      proliferation following injury. Using a BrdU incorporation assay with a short
      labeling period, we reveal high amplitude daily rhythms in S-phase in the
      epidermal cell layer of the fin under normal conditions. Peak numbers of S-phase
      cells occur at the end of the light period while lowest levels are observed at
      the end of the dark period. Remarkably, immediately following amputation the
      basal level of epidermal cell proliferation increases significantly with
      kinetics, depending upon the time of day when the amputation is performed. In
      sharp contrast, we failed to detect circadian rhythms of S-phase in the highly
      proliferative mesenchymal cells of the blastema. Subsequently, during the entire
      period of outgrowth of the new fin, elevated, cycling levels of epidermal cell
      proliferation persist. Thus, our results point to a preferential role for the
      circadian clock in the timing of epidermal cell proliferation in response to
      injury.

PMID- 22479566
TI  - The time course of segmentation and cue-selectivity in the human visual cortex.
AB  - Texture discontinuities are a fundamental cue by which the visual system segments
      objects from their background. The neural mechanisms supporting texture-based
      segmentation are therefore critical to visual perception and cognition. In the
      present experiment we employ an EEG source-imaging approach in order to study the
      time course of texture-based segmentation in the human brain. Visual Evoked
      Potentials were recorded to four types of stimuli in which periodic temporal
      modulation of a central 3 degrees  figure region could either support figure
      ground segmentation, or have identical local texture modulations but not produce
      changes in global image segmentation. The image discontinuities were defined
      either by orientation or phase differences across image regions. Evoked responses
      to these four stimuli were analyzed both at the scalp and on the cortical surface
      in retinotopic and functional regions-of-interest (ROIs) defined separately using
      fMRI on a subject-by-subject basis. Texture segmentation (tsVEP: segmenting
      versus non-segmenting) and cue-specific (csVEP: orientation versus phase)
      responses exhibited distinctive patterns of activity. Alternations between
      uniform and segmented images produced highly asymmetric responses that were
      larger after transitions from the uniform to the segmented state. Texture
      modulations that signaled the appearance of a figure evoked a pattern of
      increased activity starting at ~143 ms that was larger in V1 and LOC ROIs,
      relative to identical modulations that didn't signal figure-ground segmentation.
      This segmentation-related activity occurred after an initial response phase that
      did not depend on the global segmentation structure of the image. The two cue
      types evoked similar tsVEPs up to 230 ms when they differed in the V4 and LOC
      ROIs. The evolution of the response proceeded largely in the feed-forward
      direction, with only weak evidence for feedback-related activity.

PMID- 22479567
TI  - Seasonal dynamics of mobile carbon supply in Quercus aquifolioides at the upper
      elevational limit.
AB  - Many studies have tried to explain the physiological mechanisms of the alpine
      treeline phenomenon, but the debate on the alpine treeline formation remains
      controversial due to opposite results from different studies. The present study
      explored the carbon-physiology of an alpine shrub species (Quercus aquifolioides)
      grown at its upper elevational limit compared to lower elevations, to test
      whether the elevational limit of alpine shrubs (<3 m in height) are determined by
      carbon limitation or growth limitation. We studied the seasonal variations in non
      structural carbohydrate (NSC) and its pool size in Q. aquifolioides grown at 3000
      m, 3500 m, and at its elevational limit of 3950 m above sea level (a.s.l.) on
      Zheduo Mt., SW China. The tissue NSC concentrations along the elevational
      gradient varied significantly with season, reflecting the season-dependent carbon
      balance. The NSC levels in tissues were lowest at the beginning of the growing
      season, indicating that plants used the winter reserve storage for re-growth in
      the early spring. During the growing season, plants grown at the elevational
      limit did not show lower NSC concentrations compared to plants at lower
      elevations, but during the winter season, storage tissues, especially roots, had
      significantly lower NSC concentrations in plants at the elevational limit
      compared to lower elevations. The present results suggest the significance of
      winter reserve in storage tissues, which may determine the winter survival and
      early-spring re-growth of Q. aquifolioides shrubs at high elevation, leading to
      the formation of the uppermost distribution limit. This result is consistent with
      a recent hypothesis for the alpine treeline formation.

PMID- 22479568
TI  - The flagellar regulator fliT represses Salmonella pathogenicity island 1 through
      flhDC and fliZ.
AB  - Salmonella pathogenicity island 1 (SPI1), comprising a type III section system
      that translocates effector proteins into host cells, is essential for the enteric
      pathogen Salmonella to penetrate the intestinal epithelium and subsequently to
      cause disease. Using random transposon mutagenesis, we found that a Tn10
      disruption in the flagellar fliDST operon induced SPI1 expression when the strain
      was grown under conditions designed to repress SPI1, by mimicking the environment
      of the large intestine through the use of the intestinal fatty acid butyrate. Our
      genetic studies showed that only fliT within this operon was required for this
      effect, and that exogenous over-expression of fliT alone significantly reduced
      the expression of SPI1 genes, including the invasion regulator hilA and the
      sipBCDA operon, encoding type III section system effector proteins, and
      Salmonella invasion of cultured epithelial cells. fliT has been known to inhibit
      the flagellar machinery through repression of the flagellar master regulator
      flhDC. We found that the repressive effect of fliT on invasion genes was
      completely abolished in the absence of flhDC or fliZ, the latter previously shown
      to induce SPI1, indicating that this regulatory pathway is required for invasion
      control by fliT. Although this flhDC-fliZ pathway was necessary for fliT to
      negatively control invasion genes, fliZ was not essential for the repressive
      effect of fliT on motility, placing fliT high in the regulatory cascade for both
      invasion and motility.

PMID- 22479569
TI  - Heavy tailed distributions of effect sizes in systematic reviews of complex
      interventions.
AB  - BACKGROUND: Systematic reviews of complex interventions commonly find
      heterogeneity of effect sizes among similar interventions which cannot be
      explained. Commentators have suggested that complex interventions should be
      viewed as interventions in complex systems. We hypothesised that if this is the
      case, the distribution of effect sizes from complex interventions should be heavy
      tailed, as in other complex systems. Thus, apparent heterogeneity may be a
      feature of the complex systems in which such interventions operate.
      METHODOLOGY/PRINCIPAL FINDINGS: We specified three levels of complexity and
      identified systematic reviews which reported effect sizes of healthcare
      interventions at two of these levels (interventions to change professional
      practice and personal interventions to help smoking cessation). These were
      compared with each other and with simulated data representing the lowest level of
      complexity. Effect size data were rescaled across reviews at each level using log
      normal parameters and pooled. Distributions were plotted and fitted against the
      inverse power law (Pareto) and stretched exponential (Weibull) distributions,
      heavy tailed distributions which are commonly reported in the literature, using
      maximum likelihood fitting. The dataset included 155 studies of interventions to
      change practice and 98 studies of helping smoking cessation. Both distributions
      showed a heavy tailed distribution which fitted best to the inverse power law for
      practice interventions (exponent = 3.9, loglikelihood = -35.3) and to the
      stretched exponential for smoking cessation (loglikelihood = -75.2). Bootstrap
      sensitivity analysis to adjust for possible publication bias against weak results
      did not diminish the goodness of fit. CONCLUSIONS/SIGNIFICANCE: The distribution
      of effect sizes from complex interventions includes heavy tails as typically seen
      in both theoretical and empirical complex systems. This is in keeping with the
      idea of complex interventions as interventions in complex systems.

PMID- 22479570
TI  - Exploring the switchgrass transcriptome using second-generation sequencing
      technology.
AB  - BACKGROUND: Switchgrass (Panicum virgatum L.) is a C4 perennial grass and widely
      popular as an important bioenergy crop. To accelerate the pace of developing high
      yielding switchgrass cultivars adapted to diverse environmental niches, the
      generation of genomic resources for this plant is necessary. The large genome
      size and polyploid nature of switchgrass makes whole genome sequencing a daunting
      task even with current technologies. Exploring the transcriptional landscape
      using next generation sequencing technologies provides a viable alternative to
      whole genome sequencing in switchgrass. PRINCIPAL FINDINGS: Switchgrass cDNA
      libraries from germinating seedlings, emerging tillers, flowers, and dormant
      seeds were sequenced using Roche 454 GS-FLX Titanium technology, generating
      980,000 reads with an average read length of 367 bp. De novo assembly generated
      243,600 contigs with an average length of 535 bp. Using the foxtail millet genome
      as a reference greatly improved the assembly and annotation of switchgrass ESTs.
      Comparative analysis of the 454-derived switchgrass EST reads with other
      sequenced monocots including Brachypodium, sorghum, rice and maize indicated a 70
      80% overlap. RPKM analysis demonstrated unique transcriptional signatures of the
      four tissues analyzed in this study. More than 24,000 ESTs were identified in the
      dormant seed library. In silico analysis indicated that there are more than 2000
      EST-SSRs in this collection. Expression of several orphan ESTs was confirmed by
      RT-PCR. SIGNIFICANCE: We estimate that about 90% of the switchgrass gene space
      has been covered in this analysis. This study nearly doubles the amount of EST
      information for switchgrass currently in the public domain. The celerity and
      economical nature of second-generation sequencing technologies provide an in
      depth view of the gene space of complex genomes like switchgrass. Sequence
      analysis of closely related members of the NAD(+)-malic enzyme type C4 grasses
      such as the model system Setaria viridis can serve as a viable proxy for the
      switchgrass genome.

PMID- 22479571
TI  - Several polymorphisms of KCNQ1 gene are associated with plasma lipid levels in
      general Chinese populations.
AB  - BACKGROUND: Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1)
      is thought to be an important candidate gene of diabetes. Several single
      nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium (LD) block in
      its intron 15 have been identified to be associated with diabetes in East Asian
      populations in recent genome-wide association studies. The aim of this study was
      to investigate whether KCNQ1 polymorphisms influence the levels of the metabolic
      phenotypes in general Chinese populations. METHODOLOGY/PRINCIPAL FINDINGS: We
      investigated the associations of two SNPs (rs2237892 and rs2237895) in the
      aforementioned 40-kb LD block, a missense variant rs12720449 (P448R) in exon 10,
      and a synonymous variant rs1057128 (S546S) in exon 13 with metabolic phenotypes
      in a Uyghur population (n = 478) and replicated these associations in a Han
      population (n = 2,485). We found that rs2237892-T allele was significantly
      associated with decreased triglyceride levels (p(combined) = 0.001). The minor G
      allele of the rs12720449, with sharp difference of the allelic frequency between
      European and East Asian populations (0.2% versus 14%, respectively), was
      associated with a lower triglyceride levels than G allele in Uyghur subjects (p =
      0.004), in Han subjects (p = 0.052), and in subjects of meta-analysis
      (p(combined) = 0.001). Moreover, the minor A allele of the rs1057128 was also
      associated with decreased triglyceride levels in meta-analysis (p(combined) =
      0.010). CONCLUSIONS: To the best of our knowledge, this is the first report
      associating a missense mutation of KCNQ1, rs12720449, with triglyceride levels.
      Rs2237892, representing the 40-kb LD block, is also associated with triglyceride
      levels in Han population. Further studies are required to replicate these
      findings in other East Asian populations.

PMID- 22479572
TI  - Spironolactone lowers portal hypertension by inhibiting liver fibrosis, ROCK-2
      activity and activating NO/PKG pathway in the bile-duct-ligated rat.
AB  - OBJECTIVE: Aldosterone, one of the main peptides in renin angiotensin aldosterone
      system (RAAS), has been suggested to mediate liver fibrosis and portal
      hypertension. Spironolactone, an aldosterone antagonist, has beneficial effect on
      hyperdynamic circulation in clinical practice. However, the mechanisms remain
      unclear. The present study aimed to investigate the role of spionolactone on
      liver cirrhosis and portal hypertension. METHODS: Liver cirrhosis was induced by
      bile duct ligation (BDL). Spironolactone was administered orally (20 mg/kg/d)
      after bile duct ligation was performed. Liver fibrosis was assessed by histology,
      Masson's trichrome staining, and the measurement of hydroxyproline and type I
      collagen content. The activation of HSC was determined by analysis of alpha
      smooth muscle actin (alpha-SMA) expression. Protein expressions and protein
      phosphorylation were determined by immunohistochemical staining and Western blot
      analysis, Messenger RNA levels by quantitative real time polymerase chain
      reaction (Q-PCR). Portal pressure and intrahepatic resistance were examined in
      vivo. RESULTS: Treatment with spironolactone significantly lowered portal
      pressure. This was associated with attenuation of liver fibrosis, intrahepatic
      resistance and inhibition of HSC activation. In BDL rat liver, spironolactone
      suppressed up-regulation of proinflammatory cytokines (TNFalpha and IL-6).
      Additionally, spironolactone significantly decreased ROCK-2 activity without
      affecting expression of RhoA and Ras. Moreover, spironolactone markedly increased
      the levels of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and
      the activity of NO effector-protein kinase G (PKG) in the liver. CONCLUSION:
      Spironolactone lowers portal hypertension by improvement of liver fibrosis and
      inhibition of intrahepatic vasoconstriction via down-regulating ROCK-2 activity
      and activating NO/PKG pathway. Thus, early spironolactone therapy might be the
      optional therapy in cirrhosis and portal hypertension.

PMID- 22479573
TI  - Cell recovery in bronchoalveolar lavage fluid in smokers is dependent on
      cumulative smoking history.
AB  - BACKGROUND: Smoking is a risk factor for various lung diseases in which BAL may
      be used as a part of a clinical investigation. Interpretation of BAL fluid
      cellularity is however difficult due to high variability, in particular among
      smokers. In this study we aimed to evaluate the effect of smoking on BAL cellular
      components in asymptomatic smokers. The effects of smoking cessation, age and
      gender were also investigated in groups of smokers and exsmokers. METHODS: We
      performed a retrospective review of BAL findings, to our knowledge the largest
      single center investigation, in our department from 1999 to 2009. One hundred
      thirty two current smokers (48 males and 84 females) and 44 ex-smokers (16 males
      and 28 females) were included. A group of 295 (132 males and 163 females) never
      smokers served as reference. RESULT: The median [5-95 pctl] total number of cells
      and cell concentration in current smokers were 63.4 [28.6-132.1]*10(6) and 382.1
      [189.7-864.3]*10(6)/L respectively and correlated positively to the cumulative
      smoking history. Macrophages were the predominant cell type (96.7% [90.4-99.0])
      followed by lymphocytes (2% [0.8-7.7]) and neutrophils (0.6% [0-2.9]). The
      concentration of all inflammatory cells was increased in smokers compared to
      never smokers and ex-smokers. BAL fluid recovery was negatively correlated with
      age (p<0.001). Smoking men had a lower BAL fluid recovery than smoking women.
      CONCLUSION: Smoking has a profound effect on BAL fluid cellularity, which is
      dependent on smoking history. Our results performed on a large group of current
      smokers and ex-smokers in a well standardized way, can contribute to better
      interpretation of BAL fluid cellularity in clinical context.

PMID- 22479574
TI  - Dietary heterogeneity among Western industrialized countries reflected in the
      stable isotope ratios of human hair.
AB  - Although the globalization of food production is often assumed to result in a
      homogenization of consumption patterns with a convergence towards a Western style
      diet, the resources used to make global food products may still be locally
      produced (glocalization). Stable isotope ratios of human hair can quantify the
      extent to which residents of industrialized nations have converged on a
      standardized diet or whether there is persistent heterogeneity and glocalization
      among countries as a result of different dietary patterns and the use of local
      food products. Here we report isotopic differences among carbon, nitrogen and
      sulfur isotope ratios of human hair collected in thirteen Western European
      countries and in the USA. European hair samples had significantly lower
      delta(13)C values (-22.7 to -18.30/00), and significantly higher delta(15)N (7.8
      to 10.30/00) and delta(34)S (4.8 to 8.30/00) values than samples from the USA
      (delta(13)C: -21.9 to -15.00/00, delta(15)N: 6.7 to 9.90/00, delta(34)S: -1.2 to
      9.90/00). Within Europe, we detected differences in hair delta(13)C and
      delta(34)S values among countries and covariation of isotope ratios with latitude
      and longitude. This geographic structuring of isotopic data suggests
      heterogeneity in the food resources used by citizens of industrialized nations
      and supports the presence of different dietary patterns within Western Europe
      despite globalization trends. Here we showed the potential of stable isotope
      analysis as a population-wide tool for dietary screening, particularly as a
      complement of dietary surveys, that can provide additional information on
      assimilated macronutrients and independent verification of data obtained by those
      self-reporting instruments.

PMID- 22479575
TI  - Associations between HIV and human pathways revealed by protein-protein
      interactions and correlated gene expression profiles.
AB  - BACKGROUND: AIDS is one of the most devastating diseases in human history.
      Decades of studies have revealed host factors required for HIV infection,
      indicating that HIV exploits host processes for its own purposes. HIV infection
      leads to AIDS as well as various comorbidities. The associations between HIV and
      human pathways and diseases may reveal non-obvious relationships between HIV and
      non-HIV-defining diseases. PRINCIPAL FINDINGS: Human biological pathways were
      evaluated and statistically compared against the presence of HIV host factor
      related genes. All of the obtained scores comparing HIV targeted genes and
      biological pathways were ranked. Different rank results based on overlapping
      genes, recovered virus-host interactions, co-expressed genes, and common
      interactions in human protein-protein interaction networks were obtained.
      Correlations between rankings suggested that these measures yielded diverse
      rankings. Rank combination of these ranks led to a final ranking of HIV
      associated pathways, which revealed that HIV is associated with immune cell
      related pathways and several cancer-related pathways. The proposed method is also
      applicable to the evaluation of associations between other pathogens and human
      pathways and diseases. CONCLUSIONS: Our results suggest that HIV infection shares
      common molecular mechanisms with certain signaling pathways and cancers.
      Interference in apoptosis pathways and the long-term suppression of immune system
      functions by HIV infection might contribute to tumorigenesis. Relationships
      between HIV infection and human pathways of disease may aid in the identification
      of common drug targets for viral infections and other diseases.

PMID- 22479576
TI  - Drosophila muscleblind codes for proteins with one and two tandem zinc finger
      motifs.
AB  - Muscleblind-like proteins, Muscleblind (Mbl) in Drosophila and MBNL1-3 in
      vertebrates, are regulators of alternative splicing. Human MBNL1 is a key factor
      in the etiology of myotonic dystrophy (DM), a muscle wasting disease caused by
      the occurrence of toxic RNA molecules containing CUG/CCUG repeats. MBNL1 binds to
      these RNAs and is sequestered in nuclear foci preventing it from exerting its
      normal function, which ultimately leads to mis-spliced mRNAs, a major cause of
      the disease. Muscleblind-proteins bind to RNAs via N-terminal zinc fingers of the
      Cys(3)-His type. These zinc fingers are arranged in one (invertebrates) or two
      (vertebrates) tandem zinc finger (TZF) motifs with both fingers targeting GC
      steps in the RNA molecule. Here I show that mbl genes in Drosophila and in other
      insects also encode proteins with two TZF motifs, highly similar to vertebrate
      MBNL proteins. In Drosophila the different protein isoforms have overlapping but
      possibly divergent functions in vivo, evident by their unequal capacities to
      rescue the splicing defects observed in mbl mutant embryos. In addition, using
      whole transcriptome analysis, I identified several new splicing targets for Mbl
      in Drosophila embryos. Two of these novel targets, kkv (krotzkopf-verkehrt,
      coding for Chitin Synthase 1) and cora (coracle, coding for the Drosophila
      homolog of Protein 4.1), are not muscle-specific but expressed mainly in
      epidermal cells, indicating a function for mbl not only in muscles and the
      nervous system.

PMID- 22479577
TI  - Oligo-DNA custom macroarray for monitoring major pathogenic and non-pathogenic
      fungi and bacteria in the phyllosphere of apple trees.
AB  - BACKGROUND: To monitor the richness in microbial inhabitants in the phyllosphere
      of apple trees cultivated under various cultural and environmental conditions, we
      developed an oligo-DNA macroarray for major pathogenic and non-pathogenic fungi
      and bacteria inhabiting the phyllosphere of apple trees. METHODS AND FINDINGS:
      First, we isolated culturable fungi and bacteria from apple orchards by an agar
      plate culture method, and detected 32 fungal and 34 bacterial species.
      Alternaria, Aureobasidium, Cladosporium, Rhodotorula, Cystofilobasidium, and
      Epicoccum genera were predominant among the fungi, and Bacillus, Pseudomonas,
      Sphingomonas, Methylobacterium, and Pantoea genera were predominant among the
      bacteria. Based on the data, we selected 29 major non-pathogenic and 12
      phytopathogenic fungi and bacteria as the targets of macroarray. Forty-one
      species-specific 40-base pair long oligo-DNA sequences were selected from the
      nucleotide sequences of rDNA-internal transcribed spacer region for fungi and 16S
      rDNA for bacteria. The oligo-DNAs were fixed on nylon membrane and hybridized
      with digoxigenin-labeled cRNA probes prepared for each species. All arrays except
      those for Alternaria, Bacillus, and their related species, were specifically
      hybridized. The array was sensitive enough to detect 10(3) CFU for Aureobasidium
      pullulans and Bacillus cereus. Nucleotide sequencing of 100 each of independent
      fungal rDNA-ITS and bacterial 16S-rDNA sequences from apple tree was in agreement
      with the macroarray data obtained using the same sample. Finally, we analyzed the
      richness in the microbial inhabitants in the samples collected from apple trees
      in four orchards. Major apple pathogens that cause scab, Alternaria blotch, and
      Marssonina blotch were detected along with several non-phytopathogenic fungal and
      bacterial inhabitants. CONCLUSIONS: The macroarray technique presented here is a
      strong tool to monitor the major microbial species and the community structures
      in the phyllosphere of apple trees and identify key species antagonistic,
      supportive or co-operative to specific pathogens in the orchard managed under
      different environmental conditions.

PMID- 22479578
TI  - Influence of sex and genetic background on anxiety-related and stress-induced
      behaviour of prodynorphin-deficient mice.
AB  - The role of dynorphin/kappa opioid receptors in epilepsy and addiction are well
      accepted, but their function in emotional control is not yet fully understood.
      Data obtained from different strains of prodynorphin (Pdyn)- and kappa opioid
      receptor (KOP)-deficient mice do not provide a consistent picture of the
      functions of Dyn/KOP in anxiety, suggesting the influence of testing conditions
      and/or genetic background. Therefore, we investigated the behaviour and
      neurochemistry of male and female Pdyn KO mice on the balb/c and C57Bl/6N
      background. Consistent with our results obtained from male mice on the C57bl/6N
      background, we observed a less anxious phenotype in the elevated plus maze, open
      field and light-dark test in male mice on the balb/c background. Female mice on
      the balb/c background also displayed less anxiety like behaviour; however these
      data reflect high trait anxiety and inter-individual differences. In contrast,
      female mice on the C57Bl/6N background displayed low trait anxiety and a paradigm
      dependent reduction of anxiety. No differences were observed in the forced swim
      test, while balb/c Pdyn KO mice displayed prolonged immobility in the tail
      suspension test. In line with our previous results, we observed reduced CRH mRNA
      in the central amygdala in all groups of mice. In contrast, the recently observed
      CRH mRNA reduction in the hypothalamic paraventricular nucleus appears restricted
      to male, but not female mice. Our data support previous data suggesting a
      pronounced impact of endogenous prodynorphin-derived peptides on anxiety.
      Moreover, our data support the idea that the less anxious phenotype manifests
      only at elevated stress levels.

PMID- 22479579
TI  - Threshold-free population analysis identifies larger DRG neurons to respond
      stronger to NGF stimulation.
AB  - Sensory neurons in dorsal root ganglia (DRG) are highly heterogeneous in terms of
      cell size, protein expression, and signaling activity. To analyze their
      heterogeneity, threshold-based methods are commonly used, which often yield
      highly variable results due to the subjectivity of the individual investigator.
      In this work, we introduce a threshold-free analysis approach for sparse and
      highly heterogeneous datasets obtained from cultures of sensory neurons. This
      approach is based on population estimates and completely free of investigator-set
      parameters. With a quantitative automated microscope we measured the signaling
      state of single DRG neurons by immunofluorescently labeling phosphorylated, i.e.,
      activated Erk1/2. The population density of sensory neurons with and without pain
      sensitizing nerve growth factor (NGF) treatment was estimated using a kernel
      density estimator (KDE). By subtraction of both densities and integration of the
      positive part, a robust estimate for the size of the responsive subpopulations
      was obtained. To assure sufficiently large datasets, we determined the number of
      cells required for reliable estimates using a bootstrapping approach. The
      proposed methods were employed to analyze response kinetics and response
      amplitude of DRG neurons after NGF stimulation. We thereby determined the portion
      of NGF responsive cells on a true population basis. The analysis of the dose
      dependent NGF response unraveled a biphasic behavior, while the study of its time
      dependence showed a rapid response, which approached a steady state after less
      than five minutes. Analyzing two parameter correlations, we found that not only
      the number of responsive small-sized neurons exceeds the number of responsive
      large-sized neurons--which is commonly reported and could be explained by the
      excess of small-sized cells--but also the probability that small-sized cells
      respond to NGF is higher. In contrast, medium-sized and large-sized neurons
      showed a larger response amplitude in their mean Erk1/2 activity.

PMID- 22479580
TI  - Differences in nitrogen metabolism between Cryptococcus neoformans and C. gattii,
      the two etiologic agents of cryptococcosis.
AB  - Two members of the Cryptococcus neoformans-gattii species complex, the etiologic
      agents of cryptococcosis, can be differentiated by biological, biochemical,
      serological and molecular typing techniques. Based on their differences in carbon
      and nitrogen utilization patterns, cost effective and very specific diagnostic
      tests using D-proline and canvanine-glycine-bromthymol blue (CGB) media have been
      formulated and are widely used for identification of the two species. However,
      these methods have yet to be tested for strains with confirmed molecular types to
      assess the degree of specificity for each molecular type in the two species. We
      collected global isolates of every major molecular type available and tested
      their patterns of nitrogen utilization. We confirmed specificity of the CGB test
      to be 100% regardless of molecular type while the D-proline test yielded 8-38%
      false negative results in three of the four C. gattii molecular types, VGI-VGIII.
      The utilization pattern of a new set of amino acids: D-alanine, L-tryptophan and
      L-phenylalanine, showed species specificity comparable to that of D-proline. We
      discovered that the transcription factor Gat1 (Are1) regulates the utilization of
      nitrogen differently between C. neoformans and C. gattii strains. Unlike in C.
      neoformans, expression of the genes encoding glycine decarboxylase complex in C.
      gatti was only partially suppressed by nitrogen catabolite repression in the
      presence of ammonium. GAT1 in C. neoformans controlled the induction of three of
      the four genes encoding the glycine decarboxylase complex when glycine was used
      as the sole nitrogen source while in C. gattii its regulation of these genes was
      less stringent. Moreover, while virulence of C. neoformans strains in mice was
      not affected by Gat1, the transcription factor positively influenced the
      virulence of C. gattii strain.

PMID- 22479581
TI  - Evolution of blind beetles in isolated aquifers: a test of alternative modes of
      speciation.
AB  - Evidence is growing that not only allopatric but also sympatric speciation can be
      important in the evolution of species. Sympatric speciation has most convincingly
      been demonstrated in laboratory experiments with bacteria, but field-based
      evidence is limited to a few cases. The recently discovered plethora of
      subterranean diving beetle species in isolated aquifers in the arid interior of
      Australia offers a unique opportunity to evaluate alternative modes of
      speciation. This naturally replicated evolutionary experiment started 10-5
      million years ago, when climate change forced the surface species to occupy
      geographically isolated subterranean aquifers. Using phylogenetic analysis, we
      determine the frequency of aquifers containing closely related sister species. By
      comparing observed frequencies with predictions from different statistical
      models, we show that it is very unlikely that the high number of sympatrically
      occurring sister species can be explained by a combination of allopatric
      evolution and repeated colonisations alone. Thus, diversification has occurred
      within the aquifers and likely involved sympatric, parapatric and/or
      microallopatric speciation.

PMID- 22479582
TI  - Lower blood calcium associates with unfavorable prognosis and predicts for bone
      metastasis in NSCLC.
AB  - Ionized calcium was involved in various cellular signal pathways,and regulates
      many cellular processes, including those relevant to tumorigenesis. We hypothesis
      that imbalance of calcium homeostasis is correlated with development of lung
      carcinomas. We collected the clinical data of 1084 patients with non small cell
      lung cancer (NSCLC) treated in Shandong Provincial Hospital, Shandong University.
      Logistic regression was used to determine the association between calcium levels
      and clinical characteristics, and COX regression and Kaplan-Meier model were
      applied to analyze risk factors on overall survival. Blood electrolytes were
      tested before treatment; and nearly 16% patients with NSCLC were complained with
      decreased blood calcium, which is more frequent than that in other electrolytes.
      Further, Multivariate logistic regression analysis disclosed that there were
      significant correlation between blood calcium decrease and moderate and poor
      differentiation (P = 0.012, OR = 1.926 (1.203-4.219)), squamous cell carcinoma (P
      = 0.024, OR = 1.968(1.094-3.540)), and bone metastasis (P = 0.032, OR =
      0.396(0.235-0.669)). In multivariate COX regression analysis, advanced lymph node
      stage and decreased blood calcium were significantly and independent, unfavorable
      prognostic factors (P<0.001). Finally, the Kaplan-Meier Survival curve revealed
      that blood calcium decrease was associated with shorter survival (Log-rank;
      chi(2) = 26.172,P<0.001). Our finding indicates that lower blood calcium levels
      are associated with a higher risk of unfavorable prognosis and bone metastasis of
      NSCLC.

PMID- 22479583
TI  - Task-dependent inhomogeneous muscle activities within the bi-articular human
      rectus femoris muscle.
AB  - The motor nerve of the bi-articular rectus femoris muscle is generally split from
      the femoral nerve trunk into two sub-branches just before it reaches the distal
      and proximal regions of the muscle. In this study, we examined whether the
      regional difference in muscle activities exists within the human rectus femoris
      muscle during maximal voluntary isometric contractions of knee extension and hip
      flexion. Surface electromyographic signals were recorded from the distal, middle,
      and proximal regions. In addition, twitch responses were evoked by stimulating
      the femoral nerve with supramaximal intensity. The root mean square value of
      electromyographic amplitude during each voluntary task was normalized to the
      maximal compound muscle action potential amplitude (M-wave) for each region. The
      electromyographic amplitudes were significantly smaller during hip flexion than
      during knee extension task for all regions. There was no significant difference
      in the normalized electromyographic amplitude during knee extension among regions
      within the rectus femoris muscle, whereas those were significantly smaller in the
      distal than in the middle and proximal regions during hip flexion task. These
      results indicate that the bi-articular rectus femoris muscle is differentially
      controlled along the longitudinal direction and that in particular the distal
      region of the muscle cannot be fully activated during hip flexion.

PMID- 22479584
TI  - Intraspecific correlations of basal and maximal metabolic rates in birds and the
      aerobic capacity model for the evolution of endothermy.
AB  - The underlying assumption of the aerobic capacity model for the evolution of
      endothermy is that basal (BMR) and maximal aerobic metabolic rates are
      phenotypically linked. However, because BMR is largely a function of central
      organs whereas maximal metabolic output is largely a function of skeletal
      muscles, the mechanistic underpinnings for their linkage are not obvious.
      Interspecific studies in birds generally support a phenotypic correlation between
      BMR and maximal metabolic output. If the aerobic capacity model is valid, these
      phenotypic correlations should also extend to intraspecific comparisons. We
      measured BMR, M(sum) (maximum thermoregulatory metabolic rate) and MMR (maximum
      exercise metabolic rate in a hop-flutter chamber) in winter for dark-eyed juncos
      (Junco hyemalis), American goldfinches (Carduelis tristis; M(sum) and MMR only),
      and black-capped chickadees (Poecile atricapillus; BMR and M(sum) only) and
      examined correlations among these variables. We also measured BMR and M(sum) in
      individual house sparrows (Passer domesticus) in both summer, winter and spring.
      For both raw metabolic rates and residuals from allometric regressions, BMR was
      not significantly correlated with either M(sum) or MMR in juncos. Moreover, no
      significant correlation between M(sum) and MMR or their mass-independent
      residuals occurred for juncos or goldfinches. Raw BMR and M(sum) were
      significantly positively correlated for black-capped chickadees and house
      sparrows, but mass-independent residuals of BMR and M(sum) were not. These data
      suggest that central organ and exercise organ metabolic levels are not
      inextricably linked and that muscular capacities for exercise and shivering do
      not necessarily vary in tandem in individual birds. Why intraspecific and
      interspecific avian studies show differing results and the significance of these
      differences to the aerobic capacity model are unknown, and resolution of these
      questions will require additional studies of potential mechanistic links between
      minimal and maximal metabolic output.

PMID- 22479585
TI  - Bak compensated for Bax in p53-null cells to release cytochrome c for the
      initiation of mitochondrial signaling during Withanolide D-induced apoptosis.
AB  - The goal of cancer chemotherapy to induce multi-directional apoptosis as
      targeting a single pathway is unable to decrease all the downstream effect arises
      from crosstalk. Present study reports that Withanolide D (WithaD), a steroidal
      lactone isolated from Withania somnifera, induced cellular apoptosis in which
      mitochondria and p53 were intricately involved. In MOLT-3 and HCT116p53+/+ cells,
      WithaD induced crosstalk between intrinsic and extrinsic signaling through Bid,
      whereas in K562 and HCT116p53-/- cells, only intrinsic pathway was activated
      where Bid remain unaltered. WithaD showed pronounced activation of p53 in cancer
      cells. Moreover, lowered apoptogenic effect of HCT116p53-/- over HCT116p53+/+
      established a strong correlation between WithaD-mediated apoptosis and p53.
      WithaD induced Bax and Bak upregulation in HCT116p53+/+, whereas increase only
      Bak expression in HCT116p53-/- cells, which was coordinated with augmented p53
      expression. p53 inhibition substantially reduced Bax level and failed to inhibit
      Bak upregulation in HCT116p53+/+ cells confirming p53-dependent Bax and p53
      independent Bak activation. Additionally, in HCT116p53+/+ cells, combined loss of
      Bax and Bak (HCT116Bax-Bak-) reduced WithaD-induced apoptosis and completely
      blocked cytochrome c release whereas single loss of Bax or Bak (HCT116Bax
      Bak+/HCT116Bax+Bak-) was only marginally effective after WithaD treatment. In
      HCT116p53-/- cells, though Bax translocation to mitochondria was abrogated, Bak
      oligomerization helped the cells to release cytochrome c even before the
      disruption of mitochondrial membrane potential. WithaD also showed in vitro
      growth-inhibitory activity against an array of p53 wild type and null cancer
      cells and K562 xenograft in vivo. Taken together, WithaD elicited apoptosis in
      malignant cells through Bax/Bak dependent pathway in p53-wild type cells, whereas
      Bak compensated against loss of Bax in p53-null cells.

PMID- 22479586
TI  - Heme mediated STAT3 activation in severe malaria.
AB  - BACKGROUND: The mortality of severe malaria [cerebral malaria (CM), severe
      malaria anemia (SMA), acute lung injury (ALI) and acute respiratory distress
      syndrome (ARDS)] remains high despite the availability associated with adequate
      treatments. Recent studies in our laboratory and others have revealed a hitherto
      unknown correlation between chemokine CXCL10/CXCR3, Heme/HO-1 and STAT3 and
      cerebral malaria severity and mortality. Although Heme/HO-1 and CXCL10/CXCR3
      interactions are directly involved in the pathogenesis of CM and fatal disease,
      the mechanism dictating how Heme/HO-1 and CXCL10/CXCR3 are expressed and
      regulated under these conditions is still unknown. We therefore tested the
      hypothesis that these factors share common signaling pathways and may be mutually
      regulated. METHODS: We first clarified the roles of Heme/HO-1, CXCL10/CXCR3 and
      STAT3 in CM pathogenesis utilizing a well established experimental cerebral
      malaria mouse (ECM, P. berghei ANKA) model. Then, we further determined the
      mechanisms how STAT3 regulates HO-1 and CXCL10 as well as mutual regulation among
      them in CRL-2581, a murine endothelial cell line. RESULTS: The results
      demonstrate that (1) STAT3 is activated by P. berghei ANKA (PBA) infection in
      vivo and Heme in vitro. (2) Heme up-regulates HO-1 and CXCL10 production through
      STAT3 pathway, and regulates CXCL10 at the transcriptional level in vitro. (3) HO
      1 transcription is positively regulated by CXCL10. (4) HO-1 regulates STAT3
      signaling. CONCLUSION: Our data indicate that Heme/HO-1, CXCL10/CXCR3 and STAT3
      molecules as well as related signaling pathways play very important roles in the
      pathogenesis of severe malaria. We conclude that these factors are mutually
      regulated and provide new opportunities to develop potential novel therapeutic
      targets that could be used to supplement traditional prophylactics and treatments
      for malaria and improve clinical outcomes while reducing malaria mortality. Our
      ultimate goal is to develop novel therapies targeting Heme or CXCL10-related
      biological signaling molecules associated with development of fatal malaria.

PMID- 22479587
TI  - NAHA, a novel hydroxamic acid-derivative, inhibits growth and angiogenesis of
      breast cancer in vitro and in vivo.
AB  - BACKGROUND: We have recently synthesized novel N-alkylated amino acid-derived
      hydroxamate, 2-[Benzyl-(2-nitro-benzenesulfonyl)-amino]-N-hydroxy-3-methyl-N
      propyl-butyramide (NAHA). Here, we evaluate the anticancer activity of NAHA
      against highly invasive human breast cancer cells MDA-MB-231 in vitro and in
      vivo. METHODOLOGY/PRINCIPAL FINDINGS: Cell growth was evaluated by MTT and soft
      agar assays. Protein expression was determined by DNA microarray and Western blot
      analysis. Metastatic potential was evaluated by cell adhesion, migration,
      invasion, capillary morphogenesis, and ELISA assays. The anticancer activity in
      vivo was evaluated in mouse xenograft model. NAHA inhibited proliferation and
      colony formation of MDA-MB-231 cells together with the down-regulation of
      expression of Cdk2 and CDC20 proteins. NAHA inhibited cell adhesion, migration,
      and invasion through the suppression of secretion of uPA. NAHA suppressed
      secretion of VEGF from MDA-MB-231 cells and inhibited capillary morphogenesis of
      human aortic endothelial cells (HAECs). Finally, NAHA at 50 mg/kg was not toxic
      and decreased tumor volume and tumor weight in vivo. This suppression of tumor
      growth was associated with the inhibition of mitotic figures and induction of
      apoptosis, and the reduction of CD31 and VEGF positive cells in tumors.
      CONCLUSION: NAHA could be a novel promising compound for the development of new
      drugs for the therapy of invasive breast cancers.

PMID- 22479588
TI  - Population differences in transcript-regulator expression quantitative trait
      loci.
AB  - Gene expression quantitative trait loci (eQTL) are useful for identifying single
      nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic
      variant may be associated with a master regulator involved in the manifestation
      of a disease. The downstream target genes of the master regulator are typically
      co-expressed and share biological function. Therefore, it is practical to screen
      for eQTLs by identifying SNPs associated with the targets of a transcript
      regulator (TR). We used a multivariate regression with the gene expression of
      known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African
      (YRI) HapMap populations. A nominal p-value of <1*10(-6) revealed 234 SNPs in CEU
      and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and
      39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a
      false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene)
      in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in
      Pcnxl2 was found to be associated with the genes regulated by CREM whereas in
      YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To
      infer the pathways that regulate expression, we ranked TReQTLs by connectivity
      within the structure of biological process subtrees. One TReQTL SNP (rs3790904)
      in CEU maps to Lphn2 and is associated (nominal p-value = 8.1*10(-7)) with the
      targets of the X-linked breast cancer suppressor Foxp3. The structure of the
      biological process subtree and a gene interaction network of the TReQTL revealed
      that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors
      signaling may play a central role as communicators in Foxp3 functional
      regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned
      from integrating mRNA-Seq data and SNP-set enrichment into the analysis.

PMID- 22479589
TI  - Effects of chronic calorie restriction or dietary resveratrol supplementation on
      insulin sensitivity markers in a primate, Microcebus murinus.
AB  - The prevalence of diabetes and hyperinsulinemia increases with age, inducing
      metabolic failure and limiting lifespan. Calorie restriction (CR) without
      malnutrition delays the aging process, but its long-term application to humans
      seems difficult. Resveratrol (RSV), a dietary polyphenol, appears to be a
      promising CR mimetic that can be easily administered in humans. In this work, we
      hypothesized that both CR and RSV impact insulin sensitivity in a non-human
      primate compared to standard-fed control (CTL) animals. Four- to five-year-old
      male grey mouse lemurs (Microcebus murinus) were assigned to three dietary
      groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a
      RSV group receiving the CTL diet supplemented with RSV (200 mg.day(-1).kg(-1)).
      Insulin sensitivity and glycemia were assessed using an oral glucose tolerance
      test (OGTT) and the homeostasis model assessment of insulin resistance (HOMA-IR
      index) evaluation after 21 or 33 months of chronic treatment. Resting metabolic
      rate was also measured to assess the potential relationships between this energy
      expenditure parameter and insulin sensitivity markers. No differences were found
      after a 21-month period of treatment, except for lower glucose levels 30 min
      after glucose loading in CR animals. After 33 months, CR and RSV decreased
      glycemia after the oral glucose loading without decreasing fasting blood insulin.
      A general effect of treatment was observed on the HOMA-IR index, with an 81%
      reduction in CR animals and 53% in RSV animals after 33 months of treatment
      compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin
      sensitivity by improving the glucose tolerance of animals without disturbing
      their baseline insulin secretion. These results suggest that both CR and RSV have
      beneficial effects on metabolic alterations, although these effects are different
      in amplitude between the two anti-aging treatments and potentially rely on
      different metabolic changes.

PMID- 22479590
TI  - Astrocytic alphaVbeta3 integrin inhibits neurite outgrowth and promotes
      retraction of neuronal processes by clustering Thy-1.
AB  - Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of
      neuronal processes. However, its precise function has remained obscure, because
      its endogenous ligand is unknown. We previously showed that Thy-1 binds directly
      to alpha(V)beta(3) integrin in trans eliciting responses in astrocytes.
      Nonetheless, whether alpha(V)beta(3) integrin might also serve as a Thy-1-ligand
      triggering a neuronal response has not been explored. Thus, utilizing primary
      neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of
      alpha(V)beta(3) integrin on growth and retraction of neuronal processes were
      tested. In astrocyte-neuron co-cultures, endogenous alpha(V)beta(3) integrin
      restricted neurite outgrowth. Likewise, alpha(V)beta(3)-Fc was sufficient to
      suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In
      differentiating primary neurons exposed to alpha(V)beta(3)-Fc, fewer and shorter
      dendrites were detected. This effect was abolished by cleavage of Thy-1 from the
      neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC).
      Moreover, alpha(V)beta(3)-Fc also induced retraction of already extended Thy-1(+)
      axon-like neurites in differentiated CAD cells as well as of axonal terminals in
      differentiated primary neurons. Axonal retraction occurred when redistribution
      and clustering of Thy-1 molecules in the plasma membrane was induced by
      alpha(V)beta(3) integrin. Binding of alpha(V)beta(3)-Fc was detected in Thy-1
      clusters during axon retraction of primary neurons. Moreover, alpha(V)beta(3)-Fc
      induced Thy-1 clustering correlated in time and space with redistribution and
      inactivation of Src kinase. Thus, our data indicates that alpha(V)beta(3)
      integrin is a ligand for Thy-1 that upon binding not only restricts the growth of
      neurites, but also induces retraction of already existing processes by inducing
      Thy-1 clustering. We propose that these events participate in bi-directional
      astrocyte-neuron communication relevant to axonal repair after neuronal damage.

PMID- 22479591
TI  - GABA(A)-mediated inhibition modulates stimulus-specific adaptation in the
      inferior colliculus.
AB  - The ability to detect novel sounds in a complex acoustic context is crucial for
      survival. Neurons from midbrain through cortical levels adapt to repetitive
      stimuli, while maintaining responsiveness to rare stimuli, a phenomenon called
      stimulus-specific adaptation (SSA). The site of origin and mechanism of SSA are
      currently unknown. We used microiontophoretic application of gabazine to examine
      the role of GABA(A)-mediated inhibition in SSA in the inferior colliculus, the
      midbrain center for auditory processing. We found that gabazine slowed down the
      process of adaptation to high probability stimuli but did not abolish it, with
      response magnitude and latency still depending on the probability of the
      stimulus. Blocking GABA(A) receptors increased the firing rate to high and low
      probability stimuli, but did not completely equalize the responses. Together,
      these findings suggest that GABA(A)-mediated inhibition acts as a gain control
      mechanism that enhances SSA by modifying the responsiveness of the neuron.

PMID- 22479592
TI  - Derlin-1 deficiency is embryonic lethal, Derlin-3 deficiency appears normal, and
      Herp deficiency is intolerant to glucose load and ischemia in mice.
AB  - Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER)
      causes a cellular condition called ER stress. To overcome ER stress, unfolded
      proteins are eliminated by an ER-associated degradation (ERAD) system. To explore
      the physiological requirements for ERAD-related membrane proteins in mammals, we
      generated Derlin-1-, Derlin-3-, and Herp-deficient mice by gene targeting.
      Complete loss of Derlin-1 caused embryonic lethality at around E7-E8 (early
      somite stages). In contrast, Derlin-3- and Herp-deficient mice were born alive
      with the expected Mendelian frequency, and were superficially indistinguishable
      from wild-type mice. However, in the Derlin-3- and Herp-deficient mouse organs,
      the expression levels of ERAD-related proteins were affected under both normal
      and ER stress conditions; specific effects differed among the organs. Degradation
      of ERAD substrates was reduced in the Herp-deficient liver, and Herp-deficient
      mice exhibited impaired glucose tolerance and vulnerability to brain ischemic
      injury, both of which are known to be implicated in ER stress. Our findings
      indicate that ERAD or uncharacterized functions involving Derlin-1 are essential
      in early embryonic development. Derlin-3- and Herp-deficient mice may become
      useful model animals for investigations of the physiological contribution of ERAD
      under stressful or pathological conditions.

PMID- 22479594
TI  - Olfactory sensitivity and odor structure-activity relationships for aliphatic
      carboxylic acids in CD-1 mice.
AB  - Using a conditioning paradigm, the olfactory sensitivity of CD-1 mice for a
      homologous series of aliphatic n-carboxylic acids (ethanoic acid to n-octanoic
      acid) and several of their isomeric forms was investigated. With all 14 odorants,
      the animals significantly discriminated concentrations as low as 0.03 ppm (parts
      per million) from the solvent, and with four odorants the best-scoring animals
      even detected concentrations as low as 3 ppt (parts per trillion). Analysis of
      odor structure-activity relationships showed that the correlation between
      olfactory detection thresholds of the mice for the unbranched carboxylic acids
      and carbon chain length can best be described as a U-shaped function with the
      lowest threshold values at n-butanoic acid. A significant positive correlation
      between olfactory detection thresholds and carbon chain length of the carboxylic
      acids with their branching next to the functional carboxyl group was found. In
      contrast, no such correlation was found for carboxylic acids with their branching
      at the distal end of the carbon chain relative to the functional carboxyl group.
      Finally, a significant correlation was found between olfactory detection
      thresholds and the position of the branching of the carboxylic acids. Across
      species comparisons suggest that mice are more sensitive for short-chained (C(2)
      to C(4)) aliphatic n-carboxylic acids than other mammalian species, but not for
      longer-chained ones (C(5) to C(8)). Further comparisons suggest that odor
      structure-activity relationships are both substance class- and species-specific.

PMID- 22479593
TI  - Extinction-dependent alterations in corticostriatal mGluR2/3 and mGluR7 receptors
      following chronic methamphetamine self-administration in rats.
AB  - Methamphetamine (meth) is a highly addictive and widely abused psychostimulant.
      Repeated use of meth can quickly lead to dependence, and may be accompanied by a
      variety of persistent psychiatric symptoms and cognitive impairments. The
      neuroadaptations underlying motivational and cognitive deficits produced by
      chronic meth intake remain poorly understood. Altered glutamate neurotransmission
      within the prefrontal cortex (PFC) and striatum has been linked to both
      persistent drug-seeking and cognitive dysfunction. Therefore, the current study
      investigated changes in presynaptic mGluR receptors within corticostriatal
      circuitry after extended meth self-administration. Rats self-administered meth
      (or received yoked-saline) in 1 hr/day sessions for 7 days (short-access)
      followed by 14 days of 6 hrs/day (long-access). Rats displayed a progressive
      escalation of daily meth intake up to 6 mg/kg per day. After cessation of meth
      self-administration, rats underwent daily extinction or abstinence without
      extinction training for 14 days before being euthanized. Synaptosomes from the
      medial PFC, nucleus accumbens (NAc), and the dorsal striatum (dSTR) were isolated
      and labeled with membrane-impermeable biotin in order to measure surface mGluR2/3
      and mGluR7 receptors. Extended access to meth self-administration followed by
      abstinence decreased surface and total levels of mGluR2/3 receptors in the NAc
      and dSTR, while in the PFC, only a loss of surface mGluR2/3 and mGluR7 receptors
      was detected. Daily extinction trials reversed the downregulation of mGluR2/3
      receptors in the NAc and dSTR and mGluR7 in the PFC, but downregulation of
      surface mGluR2/3 receptors in the PFC was present regardless of post-meth
      experience. Thus, extinction learning can selectively restore some populations of
      downregulated mGluRs after prolonged exposure to meth. The present findings could
      have implications for our understanding of the persistence (or recovery) of meth
      induced motivational and cognitive deficits.

PMID- 22479595
TI  - Simple display system of mechanical properties of cells and their dispersion.
AB  - The mechanical properties of cells are unique indicators of their states and
      functions. Though, it is difficult to recognize the degrees of mechanical
      properties, due to small size of the cell and broad distribution of the
      mechanical properties. Here, we developed a simple virtual reality system for
      presenting the mechanical properties of cells and their dispersion using a haptic
      device and a PC. This system simulates atomic force microscopy (AFM)
      nanoindentation experiments for floating cells in virtual environments. An
      operator can virtually position the AFM spherical probe over a round cell with
      the haptic handle on the PC monitor and feel the force interaction. The Young's
      modulus of mesenchymal stem cells and HEK293 cells in the floating state was
      measured by AFM. The distribution of the Young's modulus of these cells was
      broad, and the distribution complied with a log-normal pattern. To represent the
      mechanical properties together with the cell variance, we used log-normal
      distribution-dependent random number determined by the mode and variance values
      of the Young's modulus of these cells. The represented Young's modulus was
      determined for each touching event of the probe surface and the cell object, and
      the haptic device-generating force was calculated using a Hertz model
      corresponding to the indentation depth and the fixed Young's modulus value. Using
      this system, we can feel the mechanical properties and their dispersion in each
      cell type in real time. This system will help us not only recognize the degrees
      of mechanical properties of diverse cells but also share them with others.

PMID- 22479596
TI  - A knockout of the Tsg101 gene leads to decreased expression of ErbB receptor
      tyrosine kinases and induction of autophagy prior to cell death.
AB  - The Tumor Susceptibility Gene 101 (Tsg101) encodes a multi-domain protein that
      mediates a variety of molecular and biological processes including the
      trafficking and lysosomal degradation of cell surface receptors. Conventional and
      conditional knockout models have demonstrated an essential requirement of this
      gene for cell cycle progression and cell viability, but the consequences of a
      complete ablation of Tsg101 on intracellular processes have not been examined to
      date. In this study, we employed mouse embryonic fibroblasts that carry two
      Tsg101 conditional knockout alleles to investigate the expression of ErbB
      receptor tyrosine kinases as well as stress-induced intracellular processes that
      are known to be associated with a defect in growth and cell survival. The
      conditional deletion of the Tsg101 gene in this well-controlled experimental
      model resulted in a significant reduction in the steady-state levels of the EGFR
      and ErbB2 but a stress-induced elevation in the phosphorylation of mitogen
      activated protein (MAP) kinases independent of growth factor stimulation. As part
      of an integrated stress response, Tsg101-deficient cells exhibited extensive
      remodeling of actin filaments and greatly enlarged lysosomes that were enriched
      with the autophagy-related protein LC3. The increase in the transcriptional
      activation and expression of LC3 and its association with Lamp1-positive
      lysosomes in a PI3K-dependent manner suggest that Tsg101 knockout cells utilize
      autophagy as a survival mechanism prior to their ultimate death. Collectively,
      this study shows that a knockout of the Tsg101 gene causes complex intracellular
      changes associated with stress response and cell death. These multifaceted
      alterations need to be recognized as they have an impact on defining particular
      functions for Tsg101 in processes such as signal transduction and
      lysosomal/endosomal trafficking.

PMID- 22479597
TI  - The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK
      signaling.
AB  - The genome of the human immunodeficiency virus type 1 (HIV-1) encodes the
      canonical retroviral proteins, as well as additional accessory proteins that
      enhance the expression of viral genes, the infectivity of the virus and the
      production of virions. The accessory Viral Protein U (Vpu), in particular,
      enhances viral particle production, while also promoting apoptosis of HIV
      infected human T lymphocytes. Some Vpu effects rely on its interaction with the
      ubiquitin-proteasome protein degradation system, but the mechanisms responsible
      for its pro-apoptotic effects in vivo are complex and remain largely to be
      elucidated.We took advantage of the Drosophila model to study the effects of Vpu
      activity in vivo. Expression of Vpu in the developing Drosophila wing provoked
      tissue loss due to caspase-dependent apoptosis. Moreover, Vpu induced expression
      of the pro-apoptotic gene reaper, known to down-regulate Inhibitor of Apoptosis
      Proteins (IAPs) which are caspase-antagonizing E3 ubiquitin ligases. Indeed, Vpu
      also reduced accumulation of Drosophila IAP1 (DIAP1). Though our results
      demonstrate a physical interaction between Vpu and the proteasome-addressing
      SLIMB/beta-TrCP protein, as in mammals, both SLIMB/betaTrCP-dependent and 
      independent Vpu effects were observed in the Drosophila wing. Lastly, the pro
      apoptotic effect of Vpu in this tissue was abrogated upon inactivation of the c
      Jun N-terminal Kinase (JNK) pathway. Our results in the fly thus provide the
      first functional evidence linking Vpu pro-apoptotic effects to activation of the
      conserved JNK pathway.

PMID- 22479598
TI  - A mathematical model for interpretable clinical decision support with
      applications in gynecology.
AB  - BACKGROUND: Over time, methods for the development of clinical decision support
      (CDS) systems have evolved from interpretable and easy-to-use scoring systems to
      very complex and non-interpretable mathematical models. In order to accomplish
      effective decision support, CDS systems should provide information on how the
      model arrives at a certain decision. To address the issue of incompatibility
      between performance, interpretability and applicability of CDS systems, this
      paper proposes an innovative model structure, automatically leading to
      interpretable and easily applicable models. The resulting models can be used to
      guide clinicians when deciding upon the appropriate treatment, estimating patient
      specific risks and to improve communication with patients. METHODS AND FINDINGS:
      We propose the interval coded scoring (ICS) system, which imposes that the effect
      of each variable on the estimated risk is constant within consecutive intervals.
      The number and position of the intervals are automatically obtained by solving an
      optimization problem, which additionally performs variable selection. The
      resulting model can be visualised by means of appealing scoring tables and color
      bars. ICS models can be used within software packages, in smartphone
      applications, or on paper, which is particularly useful for bedside medicine and
      home-monitoring. The ICS approach is illustrated on two gynecological problems:
      diagnosis of malignancy of ovarian tumors using a dataset containing 3,511
      patients, and prediction of first trimester viability of pregnancies using a
      dataset of 1,435 women. Comparison of the performance of the ICS approach with a
      range of prediction models proposed in the literature illustrates the ability of
      ICS to combine optimal performance with the interpretability of simple scoring
      systems. CONCLUSIONS: The ICS approach can improve patient-clinician
      communication and will provide additional insights in the importance and
      influence of available variables. Future challenges include extensions of the
      proposed methodology towards automated detection of interaction effects, multi
      class decision support systems, prognosis and high-dimensional data.

PMID- 22479599
TI  - Heparanase affects food intake and regulates energy balance in mice.
AB  - Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of
      severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R
      involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The
      proteoglycan can be structurally modified by the enzyme heparanase. Here we
      tested the hypothesis that heparanase plays a role in food intake behaviour and
      energy balance regulation by analysing body weight, body composition and food
      intake in genetically modified mice that either lack or overexpress heparanase.
      We also assessed food intake and body weight following acute central
      intracerebroventricular administration of heparanase; such treatment reduced food
      intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By
      contrast, heparanase knockout mice on a high-fat diet showed increased food
      intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice
      overexpressing heparanase displayed essentially the opposite phenotypes, with a
      reduced fat mass. These results implicate heparanase in energy balance control
      via the central melanocortin system. Our data indicate that heparanase acts as a
      negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate
      chains presumably linked to syndecan-3.

PMID- 22479600
TI  - Mitochondrial dysfunction and adipogenic reduction by prohibitin silencing in 3T3
      L1 cells.
AB  - Increase in mitochondrial biogenesis has been shown to accompany brown and white
      adipose cell differentiation. Prohibitins (PHBs), comprised of two evolutionarily
      conserved proteins, prohibitin-1 (PHB1) and prohibitin-2 (PHB2), are present in a
      high molecular-weight complex in the inner membrane of mitochondria. However,
      little is known about the effect of mitochondrial PHBs in adipogenesis. In the
      present study, we demonstrate that the levels of both PHB1 and PHB2 are
      significantly increased during adipogenesis of 3T3-L1 preadipocytes, especially
      in mitochondria. Knockdown of PHB1 or PHB2 by oligonucleotide siRNA significantly
      reduced the expression of adipogenic markers, the accumulation of lipids and the
      phosphorylation of extracellular signal-regulated kinases. In addition,
      fragmentation of mitochondrial reticulum, loss of mitochondrial cristae,
      reduction of mitochondrial content, impairment of mitochondrial complex I
      activity and excessive production of ROS were observed upon PHB-silencing in 3T3
      L1 cells. Our results suggest that PHBs are critical mediators in promoting 3T3
      L1 adipocyte differentiation and may be the potential targets for obesity
      therapies.

PMID- 22479601
TI  - The respiratory syncytial virus G protein conserved domain induces a persistent
      and protective antibody response in rodents.
AB  - Respiratory syncytial virus (RSV) is an important cause of severe upper and lower
      respiratory disease in infants and in the elderly. There are 2 main RSV subtypes
      A and B. A recombinant vaccine was designed based on the central domain of the
      RSV-A attachment G protein which we had previously named G2Na (aa130-230). Here
      we evaluated immunogenicity, persistence of antibody (Ab) response and protective
      efficacy induced in rodents by: (i) G2Na fused to DT (Diphtheria toxin) fragments
      in cotton rats. DT fusion did not potentiate neutralizing Ab responses against
      RSV-A or cross-reactivity to RSV-B. (ii) G2Nb (aa130-230 of the RSV-B G protein)
      either fused to, or admixed with G2Na. G2Nb did not induce RSV-B-reactive Ab
      responses. (iii) G2Na at low doses. Two injections of 3 ug G2Na in Alum were
      sufficient to induce protective immune responses in mouse lungs, preventing RSV-A
      and greatly reducing RSV-B infections. In cotton rats, G2Na-induced RSV-reactive
      Ab and protective immunity against RSV-A challenge that persisted for at least 24
      weeks. (iv) injecting RSV primed mice with a single dose of G2Na/Alum or
      G2Na/PLGA [poly(D,L-lactide-co-glycolide]. Despite the presence of pre-existing
      RSV-specific Abs, these formulations effectively boosted anti-RSV Ab titres and
      increased Ab titres persisted for at least 21 weeks. Affinity maturation of these
      Abs increased from day 28 to day 148. These data indicate that G2Na has potential
      as a component of an RSV vaccine formulation.

PMID- 22479602
TI  - Gas-filled phospholipid nanoparticles conjugated with gadolinium play a role as a
      potential theragnostics for MR-guided HIFU ablation.
AB  - To develop a long-circulating theragnostics, meaning therapeutics and diagnostics
      for MR-guided HIFU ablation, we designed and prepared Gd-C(5)F(12)-phospholipid
      nanobubbles (PLNs) 30-100 nm in diameter. The biochemical and physical
      characterization of Gd-C(5)F(12)-PLNs were performed. Since Gd-C(5)F(12)-PLN-50
      (Phi = 50 nm) and Gd-C(5)F(12)-PLN-100 (Phi = 100 nm) enhanced the hyperthermal
      effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom,
      its circulation, distribution, tumor accumulation and tumor ablation were
      examined in tumor-bearing mice. The plasma-half life of Gd-C(5)F(12)-PLNs was
      longer than 1.5 hrs. Gd-C(5)F(12)-PLNs mainly accumulated in the liver and the
      spleen, suggesting that they are slowly secreted through the hepatobiliary
      pathway. Monitored by the T1 signal intensity of MR, Gd-C(5)F(12)-PLNs
      accumulated in tumor tissues for 8 hours in mice. HIFU with Gd-C(5)F(12)-PLN-100
      showed the increased tumor ablation area as compared with HIFU alone. The results
      suggest that Gd-C(5)F(12)-PLNs exhibit a potential theragnostics for MR-guided
      HIFU ablation.

PMID- 22479603
TI  - Pathogen-specific circulating plasmablasts in patients with pneumonia.
AB  - Lower respiratory tract infections (LRTI) are the leading cause of death world
      wide, with Streptococcus pneumoniae (Pnc) as the most prevalent pathogen. Local
      immune mechanisms appear central to protection against the disease, yet they are
      poorly characterized. Infections at other, non-respiratory mucosal sites are
      associated with a transient circulation of mucosa-originating lymphocytes from
      the mucosal site to blood and back to the mucosa. The present study explored
      whether pathogen-specific plasmablasts appear in the circulation also in patients
      with infection of the lower respiratory tract. 16 patients with bacteremic Pnc
      pneumonia and 14 healthy volunteers were explored for circulating plasmablasts
      secreting antibodies against their own pathogenic Pnc strain isolated in blood
      cultures (patients) or against several pathogenic strains from pneumonia patients
      (14 controls) or a mixture of nine different purified pneumococcal
      polysaccharides (8 controls). Both patients and volunteers were studied for all
      plasmablasts. The cells were identified with ELISPOT as Pnc-specific antibody
      secreting cells (ASC) and as all immunoglobulin-secreting cells (ISC). High
      numbers of circulating Pnc-specific ASC were found in the acute phase of the
      disease in all patients with pneumonia (median 97 ASC/10(6) PBMC), but in none of
      the controls. IgG isotype predominated in 9/16 patients. The numbers of ISC were
      significantly higher in the patients than in the healthy controls, yet Pnc
      specific ASC only accounted for 0.7% of all the patients' ISC.The present study
      is the first to show that antigen-specific plasmablasts appear in the circulation
      in pneumonia, suggesting that pulmonary lypmhocytes recirculate in humans.
      Assessing these cells provides a novel tool for studying immune response to
      antigens encountered at the LRT.

PMID- 22479604
TI  - Adaptation-dependent synchronous activity contributes to receptive field size
      change of bullfrog retinal ganglion cell.
AB  - Nearby retinal ganglion cells of similar functional subtype have a tendency to
      discharge spikes in synchrony. The synchronized activity is involved in encoding
      some aspects of visual input. On the other hand, neurons always continuously
      adjust their activities in adaptation to some features of visual stimulation,
      including mean ambient light, contrast level, etc. Previous studies on adaptation
      were primarily focused on single neuronal activity, however, it is also
      intriguing to investigate the adaptation process in population neuronal
      activities. In the present study, by using multi-electrode recording system, we
      simultaneously recorded spike discharges from a group of dimming detectors (OFF
      sustained type ganglion cells) in bullfrog retina. The changes in receptive field
      properties and synchronization strength during contrast adaptation were analyzed.
      It was found that, when perfused using normal Ringer's solution, single neuronal
      receptive field size was reduced during contrast adaptation, which was
      accompanied by weakening in synchronization strength between adjacent neurons'
      activities. When dopamine (1 uM) was applied, the adaptation-related receptive
      field area shrinkage and synchronization weakening were both eliminated. The
      activation of D1 receptor was involved in the adaptation-related modulation of
      synchronization and receptive field. Our results thus suggest that the size of
      single neuron's receptive field is positively related to the strength of its
      synchronized activity with its neighboring neurons, and the dopaminergic pathway
      is responsible for the modulation of receptive field property and synchronous
      activity of the ganglion cells during the adaptation process.

PMID- 22479605
TI  - Regression with empirical variable selection: description of a new method and
      application to ecological datasets.
AB  - Despite recent papers on problems associated with full-model and stepwise
      regression, their use is still common throughout ecological and environmental
      disciplines. Alternative approaches, including generating multiple models and
      comparing them post-hoc using techniques such as Akaike's Information Criterion
      (AIC), are becoming more popular. However, these are problematic when there are
      numerous independent variables and interpretation is often difficult when
      competing models contain many different variables and combinations of variables.
      Here, we detail a new approach, REVS (Regression with Empirical Variable
      Selection), which uses all-subsets regression to quantify empirical support for
      every independent variable. A series of models is created; the first containing
      the variable with most empirical support, the second containing the first
      variable and the next most-supported, and so on. The comparatively small number
      of resultant models (n = the number of predictor variables) means that post-hoc
      comparison is comparatively quick and easy. When tested on a real dataset-
      habitat and offspring quality in the great tit (Parus major)--the optimal REVS
      model explained more variance (higher R(2)), was more parsimonious (lower AIC),
      and had greater significance (lower P values), than full, stepwise or all-subsets
      models; it also had higher predictive accuracy based on split-sample validation.
      Testing REVS on ten further datasets suggested that this is typical, with R(2)
      values being higher than full or stepwise models (mean improvement = 31% and 7%,
      respectively). Results are ecologically intuitive as even when there are several
      competing models, they share a set of "core" variables and differ only in
      presence/absence of one or two additional variables. We conclude that REVS is
      useful for analysing complex datasets, including those in ecology and
      environmental disciplines.

PMID- 22479606
TI  - Analysis of immunoglobulin transcripts in the ostrich Struthio camelus, a
      primitive avian species.
AB  - Previous studies on the immunoglobulin (Ig) genes in avian species are limited
      (mainly to galliformes and anseriformes) but have revealed several interesting
      features, including the absence of the IgD and Igkappa encoding genes, inversion
      of the IgA encoding gene and the use of gene conversion as the primary mechanism
      to generate an antibody repertoire. To better understand the Ig genes and their
      evolutionary development in birds, we analyzed the Ig genes in the ostrich
      (Struthio camelus), which is one of the most primitive birds. Similar to the
      chicken and duck, the ostrich expressed only three IgH chain isotypes (IgM, IgA
      and IgY) and lambda light chains. The IgM and IgY constant domains are similar to
      their counterparts described in other vertebrates. Although conventional IgM, IgA
      and IgY cDNAs were identified in the ostrich, we also detected a transcript
      encoding a short membrane-bound form of IgA (lacking the last two C(H) exons)
      that was undetectable at the protein level. No IgD or kappa encoding genes were
      identified. The presence of a single leader peptide in the expressed heavy chain
      and light chain V regions indicates that gene conversion also plays a major role
      in the generation of antibody diversity in the ostrich. Because the ostrich is
      one of the most primitive living aves, this study suggests that the distinct
      features of the bird Ig genes appeared very early during the divergence of the
      avian species and are thus shared by most, if not all, avian species.

PMID- 22479607
TI  - Analysis of IL12B gene variants in inflammatory bowel disease.
AB  - BACKGROUND: IL12B encodes the p40 subunit of IL-12, which is also part of IL-23.
      Recent genome-wide association studies identified IL12B and IL23R as
      susceptibility genes for inflammatory bowel disease (IBD). However, the
      phenotypic effects and potential gene-gene interactions of IL12B variants are
      largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed IL12B gene variants
      regarding association with Crohn's disease (CD) and ulcerative colitis (UC).
      Genomic DNA from 2196 individuals including 913 CD patients, 318 UC patients and
      965 healthy, unrelated controls was analyzed for four SNPs in the IL12B gene
      region (rs3212227, rs17860508, rs10045431, rs6887695). Our analysis revealed an
      association of the IL12B SNP rs6887695 with susceptibility to IBD (p = 0.035; OR
      1.15 [95% CI 1.01-1.31] including a trend for rs6887695 for association with CD
      (OR 1.41; [0.99-1.31], p = 0.066) and UC (OR 1.18 [0.97-1.43], p = 0.092). CD
      patients, who were homozygous C/C carriers of this SNP, had significantly more
      often non-stricturing, non-penetrating disease than carriers of the G allele (p =
      6.8*10(-5); OR = 2.84, 95% CI 1.66-4.84), while C/C homozygous UC patients had
      less often extensive colitis than G allele carriers (p = 0.029; OR = 0.36, 95% CI
      0.14-0.92). In silico analysis predicted stronger binding of the minor C allele
      of rs6887695 to the transcription factor RORalpha which is involved in Th17
      differentiation. Differences regarding the binding to the major and minor allele
      sequence of rs6887695 were also predicted for the transcription factors HSF1,
      HSF2, MZF1 and Oct-1. Epistasis analysis revealed weak epistasis of the IL12B SNP
      rs6887695 with several SNPs (rs11889341, rs7574865, rs7568275, rs8179673,
      rs10181656, rs7582694) in the STAT4 gene which encodes the major IL-12 downstream
      transcription factor STAT4 (p<0.05) but there was no epistasis between IL23R and
      IL12B variants. CONCLUSIONS/SIGNIFICANCE: The IL12B SNP rs6887695 modulates the
      susceptibility and the phenotype of IBD, although the effect on IBD susceptibilty
      is less pronounced than that of IL23R gene variants.

PMID- 22479608
TI  - Glyoxalase-I is a novel prognosis factor associated with gastric cancer
      progression.
AB  - Glyoxalase I (GLO1), a methylglyoxal detoxification enzyme, is implicated in the
      progression of human malignancies. The role of GLO1 in gastric cancer development
      or progression is currently unclear. The expression of GLO1 was determined in
      primary gastric cancer specimens using quantitative polymerase chain reaction,
      immunohistochemistry (IHC), and western blotting analyses. GLO1 expression was
      higher in gastric cancer tissues, compared with that in adjacent noncancerous
      tissues. Elevated expression of GLO1 was significantly associated with gastric
      wall invasion, lymph node metastasis, and pathological stage, suggesting a novel
      role of GLO1 in gastric cancer development and progression. The 5-year survival
      rate of the lower GLO1 expression groups was significantly greater than that of
      the higher expression groups (log rank P = 0.0373) in IHC experiments. Over
      expression of GLO1 in gastric cancer cell lines increases cell proliferation,
      migration and invasiveness. Conversely, down-regulation of GLO1 with shRNA led to
      a marked reduction in the migration and invasion abilities. Our data strongly
      suggest that high expression of GLO1 in gastric cancer enhances the metastasis
      ability of tumor cells in vitro and in vivo, and support its efficacy as a
      potential marker for the detection and prognosis of gastric cancer.

PMID- 22479609
TI  - High viral load of human bocavirus correlates with duration of wheezing in
      children with severe lower respiratory tract infection.
AB  - BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus and
      increasing evidences are available to support its role as an etiologic agent in
      lower respiratory tract infection (LRTI). The objective of this study is to
      assess the impact of HBoV viral load on clinical characteristics in children who
      were HBoV positive and suffered severe LRTI. METHODS: Lower respiratory tract
      aspirates from 186 hospitalized children with severe LRTI were obtained by
      bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents
      were examined using PCR and/or direct fluorescent assay. RESULTS: Thirty-one
      patients (24.6%) were tested positive for HBoV in the respiratory tract
      aspirates. Fifteen samples had a high viral load (>10(4) copies/mL) and the other
      sixteen samples had a low viral load (<10(4) copies/mL). The duration of
      presented wheezing and hospitalization was longer in children with high viral
      load of HBoV than that in children with low viral load. The days of wheezing
      showed a correlation with viral load of HBoV. CONCLUSION: We confirmed that HBoV
      was frequently detected in patients with severe LRTI. Wheezing was one of the
      most common symptoms presented by patients with positive HBoV. A high HBoV viral
      load could be an etiologic agent for LRTI, which led to more severe lower
      respiratory tract symptom, longer duration of wheezing and hospitalization.

PMID- 22479610
TI  - Experimental study of informal rewards in peer production.
AB  - We test the effects of informal rewards in online peer production. Using a
      randomized, experimental design, we assigned editing awards or "barnstars" to a
      subset of the 1% most productive Wikipedia contributors. Comparison with the
      control group shows that receiving a barnstar increases productivity by 60% and
      makes contributors six times more likely to receive additional barnstars from
      other community members, revealing that informal rewards significantly impact
      individual effort.

PMID- 22479611
TI  - Temperature, but not available energy, affects the expression of a sexually
      selected ultraviolet (UV) colour trait in male European green lizards.
AB  - BACKGROUND: Colour signals are widely used in intraspecific communication and
      often linked to individual fitness. The development of some pigment-based (e.g.
      carotenoids) colours is often environment-dependent and costly for the signaller,
      however, for structural colours (e.g. ultraviolet [UV]) this topic is poorly
      understood, especially in terrestrial ectothermic vertebrates.
      METHODOLOGY/PRINCIPAL FINDINGS: In a factorial experiment, we studied how
      available energy and time at elevated body temperature affects the annual
      expression of the nuptial throat colour patch in male European green lizards
      (Lacerta viridis) after hibernation and before mating season. In this species,
      there is a female preference for males with high throat UV reflectance, and males
      with high UV reflectance are more likely to win fights. We found that (i) while
      food shortage decreased lizards' body condition, it did not affect colour
      development, and (ii) the available time for maintaining high body temperature
      affected the development of UV colour without affecting body condition or other
      colour traits. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the
      expression of a sexually selected structural colour signal depends on the time at
      elevated body temperature affecting physiological performance but not on
      available energy gained from food per se in an ectothermic vertebrate. We suggest
      that the effect of high ambient temperature on UV colour in male L. viridis makes
      it an honest signal, because success in acquiring thermally favourable
      territories and/or effective behavioural thermoregulation can both be linked to
      individual quality.

PMID- 22479612
TI  - Isosteviol has beneficial effects on palmitate-induced alpha-cell dysfunction and
      gene expression.
AB  - BACKGROUND: Long-term exposure to high levels of fatty acids impairs insulin
      secretion and exaggerates glucagon secretion. The aim of this study was to
      explore if the antihyperglycemic agent, Isosteviol (ISV), is able to counteract
      palmitate-induced alpha-cell dysfunction and to influence alpha-cell gene
      expression. METHODOLOGY/PRINCIPAL FINDINGS: Long-term incubation studies with
      clonal alpha-TC1-6 cells were performed in the presence of 0.5 mM palmitate with
      or without ISV. We investigated effects on glucagon secretion, glucagon content,
      cellular triglyceride (TG) content, cell proliferation, and expression of genes
      involved in controlling glucagon synthesis, fatty acid metabolism, and insulin
      signal transduction. Furthermore, we studied effects of ISV on palmitate-induced
      glucagon secretion from isolated mouse islets. Culturing alpha-cells for 72-h
      with 0.5 mM palmitate in the presence of 18 mM glucose resulted in a 56% (p<0.01)
      increase in glucagon secretion. Concomitantly, the TG content of alpha-cells
      increased by 78% (p<0.01) and cell proliferation decreased by 19% (p<0.05). At 18
      mM glucose, ISV (10(-8) and 10(-6) M) reduced palmitate-stimulated glucagon
      release by 27% (p<0.05) and 27% (p<0.05), respectively. ISV (10(-6) M) also
      counteracted the palmitate-induced hypersecretion of glucagon in mouse islets.
      ISV (10(-6) M) reduced alpha-TC1-6 cell proliferation rate by 25% (p<0.05), but
      ISV (10(-8) and 10(-6) M) had no effect on TG content in the presence of
      palmitate. Palmitate (0.5 mM) increased Pcsk2 (p<0.001), Irs2 (p<0.001), Fasn
      (p<0.001), Srebf2 (p<0.001), Acaca (p<0.01), Pax6 (p<0.05) and Gcg mRNA
      expression (p<0.05). ISV significantly (p<0.05) up-regulated Insr, Irs1, Irs2,
      Pik3r1 and Akt1 gene expression in the presence of palmitate.
      CONCLUSIONS/SIGNIFICANCE: ISV counteracts alpha-cell hypersecretion and
      apparently contributes to changes in expression of key genes resulting from long
      term exposure to palmitate. ISV apparently acts as a glucagonostatic drug with
      potential as a new anti-diabetic drug for the treatment of type 2 diabetes.

PMID- 22479613
TI  - Genetic population structure in the Antarctic benthos: insights from the
      widespread amphipod, Orchomenella franklini.
AB  - Currently there is very limited understanding of genetic population structure in
      the Antarctic benthos. We conducted one of the first studies of microsatellite
      variation in an Antarctic benthic invertebrate, using the ubiquitous amphipod
      Orchomenella franklini (Walker, 1903). Seven microsatellite loci were used to
      assess genetic structure on three spatial scales: sites (100 s of metres),
      locations (1-10 kilometres) and regions (1000 s of kilometres) sampled in East
      Antarctica at Casey and Davis stations. Considerable genetic diversity was
      revealed, which varied between the two regions and also between polluted and
      unpolluted sites. Genetic differentiation among all populations was highly
      significant (F(ST) = 0.086, R(ST) = 0.139, p<0.001) consistent with the brooding
      mode of development in O. franklini. Hierarchical AMOVA revealed that the
      majority of the genetic subdivision occurred across the largest geographical
      scale, with N(e)m~1 suggesting insufficient gene flow to prevent independent
      evolution of the two regions, i.e., Casey and Davis are effectively isolated.
      Isolation by distance was detected at smaller scales and indicates that gene flow
      in O. franklini occurs primarily through stepping-stone dispersal. Three of the
      microsatellite loci showed signs of selection, providing evidence that localised
      adaptation may occur within the Antarctic benthos. These results provide insights
      into processes of speciation in Antarctic brooders, and will help inform the
      design of spatial management initiatives recently endorsed for the Antarctic
      benthos.

PMID- 22479614
TI  - GPS-ARM: computational analysis of the APC/C recognition motif by predicting D
      boxes and KEN-boxes.
AB  - Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase incorporated
      with Cdh1 and/or Cdc20 recognizes and interacts with specific substrates, and
      faithfully orchestrates the proper cell cycle events by targeting proteins for
      proteasomal degradation. Experimental identification of APC/C substrates is
      largely dependent on the discovery of APC/C recognition motifs, e.g., the D-box
      and KEN-box. Although a number of either stringent or loosely defined motifs
      proposed, these motif patterns are only of limited use due to their insufficient
      powers of prediction. We report the development of a novel GPS-ARM software
      package which is useful for the prediction of D-boxes and KEN-boxes in proteins.
      Using experimentally identified D-boxes and KEN-boxes as the training data sets,
      a previously developed GPS (Group-based Prediction System) algorithm was adopted.
      By extensive evaluation and comparison, the GPS-ARM performance was found to be
      much better than the one using simple motifs. With this powerful tool, we
      predicted 4,841 potential D-boxes in 3,832 proteins and 1,632 potential KEN-boxes
      in 1,403 proteins from H. sapiens, while further statistical analysis suggested
      that both the D-box and KEN-box proteins are involved in a broad spectrum of
      biological processes beyond the cell cycle. In addition, with the co-localization
      information, we predicted hundreds of mitosis-specific APC/C substrates with high
      confidence. As the first computational tool for the prediction of APC/C-mediated
      degradation, GPS-ARM is a useful tool for information to be used in further
      experimental investigations. The GPS-ARM is freely accessible for academic
      researchers at: http://arm.biocuckoo.org.

PMID- 22479615
TI  - Hedgehog signaling in tumor cells facilitates osteoblast-enhanced osteolytic
      metastases.
AB  - The remodeling process in bone yields numerous cytokines and chemokines that
      mediate crosstalk between osteoblasts and osteoclasts and also serve to attract
      and support metastatic tumor cells. The metastatic tumor cells disturb the
      equilibrium in bone that manifests as skeletal complications. The Hedgehog (Hh)
      pathway plays an important role in skeletogenesis. We hypothesized that the Hh
      pathway mediates an interaction between tumor cells and osteoblasts and
      influences osteoblast differentiation in response to tumor cells. We have
      determined that breast tumor cells have an activated Hh pathway characterized by
      upregulation of the ligand, IHH and transcription factor GLI1. Breast cancer
      cells interact with osteoblasts and cause an enhanced differentiation of pre
      osteoblasts to osteoblasts that express increased levels of the
      osteoclastogenesis factors, RANKL and PTHrP. There is sustained expression of
      osteoclast-promoting factors, RANKL and PTHrP, even after the osteoblast
      differentiation ceases and apoptosis sets in. Moreover, tumor cells that are
      deficient in Hh signaling are compromised in their ability to induce osteoblast
      differentiation and consequently are inefficient in causing osteolysis. The
      stimulation of osteoblast differentiation sets the stage for osteoclast
      differentiation and overall promotes osteolysis. Thus, in the process of
      developing newer therapeutic strategies against breast cancer metastasis to bone
      it would worthwhile to keep in mind the role of the Hh pathway in osteoblast
      differentiation in an otherwise predominant osteolytic phenomenon.

PMID- 22479616
TI  - Stochastic population dynamics of a montane ground-dwelling squirrel.
AB  - Understanding the causes and consequences of population fluctuations is a central
      goal of ecology. We used demographic data from a long-term (1990-2008) study and
      matrix population models to investigate factors and processes influencing the
      dynamics and persistence of a golden-mantled ground squirrel (Callospermophilus
      lateralis) population, inhabiting a dynamic subalpine habitat in Colorado, USA.
      The overall deterministic population growth rate lambda was 0.94+/-SE 0.05 but it
      varied widely over time, ranging from 0.45+/-0.09 in 2006 to 1.50+/-0.12 in 2003,
      and was below replacement (lambda<1) for 9 out of 18 years. The stochastic
      population growth rate lambda(s) was 0.92, suggesting a declining population;
      however, the 95% CI on lambda(s) included 1.0 (0.52-1.60). Stochastic elasticity
      analysis showed that survival of adult females, followed by survival of juvenile
      females and litter size, were potentially the most influential vital rates;
      analysis of life table response experiments revealed that the same three life
      history variables made the largest contributions to year-to year changes in
      lambda. Population viability analysis revealed that, when the influences of
      density dependence and immigration were not considered, the population had a high
      (close to 1.0 in 50 years) probability of extinction. However, probability of
      extinction declined to as low as zero when density dependence and immigration
      were considered. Destabilizing effects of stochastic forces were counteracted by
      regulating effects of density dependence and rescue effects of immigration, which
      allowed our study population to bounce back from low densities and prevented
      extinction. These results suggest that dynamics and persistence of our study
      population are determined synergistically by density-dependence, stochastic
      forces, and immigration.

PMID- 22479617
TI  - Effect of sex and prior exposure to a cafeteria diet on the distribution of sex
      hormones between plasma and blood cells.
AB  - It is generally assumed that steroid hormones are carried in the blood free
      and/or bound to plasma proteins. We investigated whether blood cells were also
      able to bind/carry sex-related hormones: estrone, estradiol, DHEA and
      testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days,
      which induced overweight. The rats were fed the standard rat diet for 15
      additional days to minimize the immediate effects of excess ingested energy.
      Controls were always kept on standard diet. After the rats were killed, their
      blood was used for 1) measuring plasma hormone levels, 2) determining the binding
      of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood
      with labeled hormones and determining the distribution of label between plasma
      and packed cells, discounting the trapped plasma volume, 4) determining free
      plasma hormone using labeled hormones, both through membrane ultrafiltration and
      dextran-charcoal removal. The results were computed individually for each rat.
      Cells retained up to 32% estrone, and down to 10% of testosterone, with marked
      differences due to sex and diet (the latter only for estrogens, not for DHEA and
      testosterone). Sex and diet also affected the concentrations of all hormones,
      with no significant diet effects for estradiol and DHEA, but with considerable
      interaction between both factors. Binding to RBC was non-specific for all
      hormones. Estrogen distribution in plasma compartments was affected by sex and
      diet. IN CONCLUSION: a) there is a large non-specific RBC-carried compartment for
      estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior
      exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes,
      affected by sex, which hint at sex-related structural differences in RBC
      membranes; c) We postulate that the RBC compartment may contribute to maintain
      free (i.e., fully active) sex hormone levels in a way similar to plasma proteins
      non-specific binding.

PMID- 22479619
TI  - Influence of different envelope maskers on signal recognition and neuronal
      representation in the auditory system of a grasshopper.
AB  - BACKGROUND: Animals that communicate by sound face the problem that the signals
      arriving at the receiver often are degraded and masked by noise. Frequency
      filters in the receiver's auditory system may improve the signal-to-noise ratio
      (SNR) by excluding parts of the spectrum which are not occupied by the species
      specific signals. This solution, however, is hardly amenable to species that
      produce broad band signals or have ears with broad frequency tuning. In mammals
      auditory filters exist that work in the temporal domain of amplitude modulations
      (AM). Do insects also use this type of filtering? PRINCIPAL FINDINGS: Combining
      behavioural and neurophysiological experiments we investigated whether AM filters
      may improve the recognition of masked communication signals in grasshoppers. The
      AM pattern of the sound, its envelope, is crucial for signal recognition in these
      animals. We degraded the species-specific song by adding random fluctuations to
      its envelope. Six noise bands were used that differed in their overlap with the
      spectral content of the song envelope. If AM filters contribute to reduced
      masking, signal recognition should depend on the degree of overlap between the
      song envelope spectrum and the noise spectra. Contrary to this prediction, the
      resistance against signal degradation was the same for five of six masker bands.
      Most remarkably, the band with the strongest frequency overlap to the natural
      song envelope (0-100 Hz) impaired acceptance of degraded signals the least. To
      assess the noise filter capacities of single auditory neurons, the changes of
      spike trains as a function of the masking level were assessed. Increasing levels
      of signal degradation in different frequency bands led to similar changes in the
      spike trains in most neurones. CONCLUSIONS: There is no indication that auditory
      neurones of grasshoppers are specialized to improve the SNR with respect to the
      pattern of amplitude modulations.

PMID- 22479618
TI  - Body context and posture affect mental imagery of hands.
AB  - Different visual stimuli have been shown to recruit different mental imagery
      strategies. However the role of specific visual stimuli properties related to
      body context and posture in mental imagery is still under debate. Aiming to
      dissociate the behavioural correlates of mental processing of visual stimuli
      characterized by different body context, in the present study we investigated
      whether the mental rotation of stimuli showing either hands as attached to a body
      (hands-on-body) or not (hands-only), would be based on different mechanisms. We
      further examined the effects of postural changes on the mental rotation of both
      stimuli. Thirty healthy volunteers verbally judged the laterality of rotated
      hands-only and hands-on-body stimuli presented from the dorsum- or the palm-view,
      while positioning their hands on their knees (front postural condition) or behind
      their back (back postural condition). Mental rotation of hands-only, but not of
      hands-on-body, was modulated by the stimulus view and orientation. Additionally,
      only the hands-only stimuli were mentally rotated at different speeds according
      to the postural conditions. This indicates that different stimulus-related
      mechanisms are recruited in mental rotation by changing the bodily context in
      which a particular body part is presented. The present data suggest that, with
      respect to hands-only, mental rotation of hands-on-body is less dependent on
      biomechanical constraints and proprioceptive input. We interpret our results as
      evidence for preferential processing of visual- rather than kinesthetic-based
      mechanisms during mental transformation of hands-on-body and hands-only,
      respectively.

PMID- 22479620
TI  - The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is
      associated with risk of asthma: a meta-analysis.
AB  - BACKGROUND: A number of studies assessed the association of -675 4G/5G
      polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1
      gene with asthma in different populations. However, most studies reported
      inconclusive results. A meta-analysis was conducted to investigate the
      association between polymorphism in the PAI-1 gene and asthma susceptibility.
      METHODS: Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang
      Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were
      searched to find relevant studies. Odds ratios (ORs) with 95% confidence
      intervals (CIs) were used to assess the strength of association in the dominant
      model, recessive model, codominant model, and additive model. RESULTS: Eight
      studies involving 1817 cases and 2327 controls were included. Overall,
      significant association between 4G/5G polymorphism and asthma susceptibility was
      observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008), 4G/4G
      vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02), 4G/4G vs. 5G/5G (OR =
      1.80, 95% CI 1.17-2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84,
      P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008). CONCLUSIONS:
      This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a
      risk factor of asthma.

PMID- 22479621
TI  - Involvement of iron in biofilm formation by Staphylococcus aureus.
AB  - Staphylococcus aureus is a human pathogen that forms biofilm on catheters and
      medical implants. The authors' earlier study established that 1,2,3,4,6-penta-O
      galloyl-beta-D-glucopyranose (PGG) inhibits biofilm formation by S. aureus by
      preventing the initial attachment of the cells to a solid surface and reducing
      the production of polysaccharide intercellular adhesin (PIA). Our cDNA microarray
      and MALDI-TOF mass spectrometric studies demonstrate that PGG treatment causes
      the expression of genes and proteins that are normally expressed under iron
      limiting conditions. A chemical assay using ferrozine verifies that PGG is a
      strong iron chelator that depletes iron from the culture medium. This study finds
      that adding FeSO(4) to a medium that contains PGG restores the biofilm formation
      and the production of PIA by S. aureus SA113. The requirement of iron for biofilm
      formation by S. aureus SA113 can also be verified using a semi-defined medium,
      BM, that contains an iron chelating agent, 2, 2'-dipyridyl (2-DP). Similar to the
      effect of PGG, the addition of 2-DP to BM medium inhibits biofilm formation and
      adding FeSO(4) to BM medium that contains 2-DP restores biofilm formation. This
      study reveals an important mechanism of biofilm formation by S. aureus SA113.

PMID- 22479622
TI  - Knockdown of Bardet-Biedl syndrome gene BBS9/PTHB1 leads to cilia defects.
AB  - Bardet-Biedl Syndrome (BBS, MIM#209900) is a genetically heterogeneous disorder
      with pleiotropic phenotypes that include retinopathy, mental retardation, obesity
      and renal abnormalities. Of the 15 genes identified so far, seven encode core
      proteins that form a stable complex called BBSome, which is implicated in
      trafficking of proteins to cilia. Though BBS9 (also known as PTHB1) is reportedly
      a component of BBSome, its direct function has not yet been elucidated. Using
      zebrafish as a model, we show that knockdown of bbs9 with specific antisense
      morpholinos leads to developmental abnormalities in retina and brain including
      hydrocephaly that are consistent with the core phenotypes observed in syndromic
      ciliopathies. Knockdown of bbs9 also causes reduced number and length of cilia in
      Kupffer's vesicle. We also demonstrate that an orthologous human BBS9 mRNA, but
      not one carrying a missense mutation identified in BBS patients, can rescue the
      bbs9 morphant phenotype. Consistent with these findings, knockdown of Bbs9 in
      mouse IMCD3 cells results in the absence of cilia. Our studies suggest a key
      conserved role of BBS9 in biogenesis and/or function of cilia in zebrafish and
      mammals.

PMID- 22479623
TI  - Peripheral immune cell gene expression predicts survival of patients with non
      small cell lung cancer.
AB  - Prediction of cancer recurrence in patients with non-small cell lung cancer
      (NSCLC) currently relies on the assessment of clinical characteristics including
      age, tumor stage, and smoking history. A better prediction of early stage cancer
      patients with poorer survival and late stage patients with better survival is
      needed to design patient-tailored treatment protocols. We analyzed gene
      expression in RNA from peripheral blood mononuclear cells (PBMC) of NSCLC
      patients to identify signatures predictive of overall patient survival. We find
      that PBMC gene expression patterns from NSCLC patients, like patterns from
      tumors, have information predictive of patient outcomes. We identify and validate
      a 26 gene prognostic panel that is independent of clinical stage. Many additional
      prognostic genes are specific to myeloid cells and are more highly expressed in
      patients with shorter survival. We also observe that significant numbers of
      prognostic genes change expression levels in PBMC collected after tumor
      resection. These post-surgery gene expression profiles may provide a means to re
      evaluate prognosis over time. These studies further suggest that patient outcomes
      are not solely determined by tumor gene expression profiles but can also be
      influenced by the immune response as reflected in peripheral immune cells.

PMID- 22479624
TI  - Improved mitochondrial function with diet-induced increase in either
      docosahexaenoic acid or arachidonic acid in membrane phospholipids.
AB  - Mitochondria can depolarize and trigger cell death through the opening of the
      mitochondrial permeability transition pore (MPTP). We recently showed that an
      increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic
      acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in
      mitochondrial membranes is associated with a greater Ca(2+) load required to
      induce MPTP opening. Here we manipulated mitochondrial phospholipid composition
      by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks.
      There were no effects on cardiac function, or respiration of isolated
      mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation
      increased DHA and displaced ARA in mitochondrial membranes, while supplementation
      with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6).
      Phospholipid analysis revealed a similar pattern, particularly in cardiolipin.
      Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA
      supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and
      ARA groups had delayed Ca(2+)-induced MPTP opening, but the DHA+ARA group was
      similar to the control diet. In conclusion, alterations in mitochondria membrane
      phospholipid fatty acid composition caused by dietary DHA or ARA was associated
      with a greater cumulative Ca(2+) load required to induced MPTP opening. Further,
      high levels of tetralinoleoyl cardiolipin were not essential for normal
      mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

PMID- 22479625
TI  - Comparative analysis of gene content evolution in phytoplasmas and mycoplasmas.
AB  - Phytoplasmas and mycoplasmas are two groups of important pathogens in the
      bacterial class Mollicutes. Because of their economical and clinical importance,
      these obligate pathogens have attracted much research attention. However,
      difficulties involved in the empirical study of these bacteria, particularly the
      fact that phytoplasmas have not yet been successfully cultivated outside of their
      hosts despite decades of attempts, have greatly hampered research progress. With
      the rapid advancements in genome sequencing, comparative genome analysis provides
      a new approach to facilitate our understanding of these bacteria. In this study,
      our main focus is to investigate the evolution of gene content in phytoplasmas,
      mycoplasmas, and their common ancestor. By using a phylogenetic framework for
      comparative analysis of 12 complete genome sequences, we characterized the
      putative gains and losses of genes in these obligate parasites. Our results
      demonstrated that the degradation of metabolic capacities in these bacteria has
      occurred predominantly in the common ancestor of Mollicutes, prior to the
      evolutionary split of phytoplasmas and mycoplasmas. Furthermore, we identified a
      list of genes that are acquired by the common ancestor of phytoplasmas and are
      conserved across all strains with complete genome sequences available. These
      genes include several putative effectors for the interactions with hosts and may
      be good candidates for future functional characterization.

PMID- 22479626
TI  - Historical temperature variability affects coral response to heat stress.
AB  - Coral bleaching is the breakdown of symbiosis between coral animal hosts and
      their dinoflagellate algae symbionts in response to environmental stress. On
      large spatial scales, heat stress is the most common factor causing bleaching,
      which is predicted to increase in frequency and severity as the climate warms.
      There is evidence that the temperature threshold at which bleaching occurs varies
      with local environmental conditions and background climate conditions. We
      investigated the influence of past temperature variability on coral
      susceptibility to bleaching, using the natural gradient in peak temperature
      variability in the Gilbert Islands, Republic of Kiribati. The spatial pattern in
      skeletal growth rates and partial mortality scars found in massive Porites sp.
      across the central and northern islands suggests that corals subject to larger
      year-to-year fluctuations in maximum ocean temperature were more resistant to a
      2004 warm-water event. In addition, a subsequent 2009 warm event had a
      disproportionately larger impact on those corals from the island with lower
      historical heat stress, as indicated by lower concentrations of triacylglycerol,
      a lipid utilized for energy, as well as thinner tissue in those corals. This
      study indicates that coral reefs in locations with more frequent warm events may
      be more resilient to future warming, and protection measures may be more
      effective in these regions.

PMID- 22479627
TI  - A crucial role of IL-17 and IFN-gamma during acute rejection of peripheral nerve
      xenotransplantation in mice.
AB  - Nerve injuries causing segmental loss require nerve grafting. However, autografts
      and allografts have limitations for clinical use. Peripheral nerve
      xenotransplantation has become an area of great interest in clinical surgery
      research as an alternative graft strategy. However, xenotransplant rejection is
      severe with cellular immunity, and Th1 cells play an important role in the
      process. To better understand the process of rejection, we used peripheral nerve
      xenografts from rats to mice and found that mononuclear cells expressing IFN
      gamma and IL-17 infiltrated around the grafts, and IFN-gamma and IL-17 producing
      CD4+ and CD8+ T cells increased during the process of acute rejection. The
      changes of IL-4 level had no significant difference between xenotransplanted
      group and sham control group. The rejection of xenograft was significantly
      prevented after the treatment of IL-17 and IFN-gamma neutralizing antibodies.
      These data suggest that Th17 cells contribute to the acute rejection process of
      peripheral nerve xenotransplant in addition to Th1 cells.

PMID- 22479628
TI  - Bluetongue virus serotype 1 outbreak in the Basque Country (Northern Spain) 2007
      2008. Data support a primary vector windborne transport.
AB  - BACKGROUND: Bluetongue (BT) is a vector-borne disease of ruminants that has
      expanded its traditional global distribution in the last decade. Recently, BTV-1
      emerged in Southern Spain and caused several outbreaks in livestock reaching the
      north of the country. The aim of this paper was to review the emergence of BTV-1
      in the Basque Country (Northern Spain) during 2007 and 2008 analyzing the
      possibility that infected Culicoides were introduced into Basque Country by winds
      from the infected areas of Southern Spain. METHODOLOGY/PRINCIPAL FINDINGS: We use
      a complex HYSPLIT (Hybrid Single-Particle Lagrangian Integrated Trajectory) model
      to draw wind roses and backward wind trajectories. The analysis of winds showed
      September 28 to October 2 as the only period for the introduction of infected
      midges in the Basque Country. These wind trajectories crossed through the areas
      affected by serotype 1 on those dates in the South of the Iberian Peninsula.
      Additionally meteorological data, including wind speed and humidity, and altitude
      along the trajectories showed suitable conditions for Culicoides survival and
      dispersion. CONCLUSIONS/SIGNIFICANCE: An active infection in medium-long distance
      regions, wind with suitable speed, altitude and trajectory, and appropriate
      weather can lead to outbreaks of BTV-1 by transport of Culicoides imicola, not
      only over the sea (as reported previously) but also over the land. This shows
      that an additional factor has to be taken into account for the control of the
      disease which is currently essentially based on the assumption that midges will
      only spread the virus in a series of short hops. Moreover, the epidemiological
      and serological data cannot rule out the involvement of other Culicoides species
      in the spread of the infection, especially at a local level.

PMID- 22479629
TI  - From Late Miocene to Holocene: processes of differentiation within the Telestes
      genus (Actinopterygii: Cyprinidae).
AB  - Investigating processes and timing of differentiation of organisms is critical in
      the understanding of the evolutionary mechanisms involved in microevolution,
      speciation, and macroevolution that generated the extant biodiversity. From this
      perspective, the Telestes genus is of special interest: the Telestes species have
      a wide distribution range across Europe (from the Danubian district to
      Mediterranean districts) and have not been prone to translocation. Molecular data
      (mtDNA: 1,232 bp including the entire Cyt b gene; nuclear genome: 11
      microsatellites) were gathered from 34 populations of the Telestes genus, almost
      encompassing the entire geographic range. Using several phylogenetic and
      molecular dating methods interpreted in conjunction with paleoclimatic and
      geomorphologic evidence, we investigated the processes and timing of
      differentiation of the Telestes lineages. The observed genetic structure and
      diversity were largely congruent between mtDNA and microsatellites. The Messinian
      Salinity Crisis (Late Miocene) seems to have played a major role in the
      speciation processes of the genus. Focusing on T. souffia, a species occurring in
      the Danube and Rhone drainages, we were able to point out several specific events
      from the Pleistocene to the Holocene that have likely driven the differentiation
      and the historical demography of this taxon. This study provides support for an
      evolutionary history of dispersal and vicariance with unprecedented resolution
      for any freshwater fish in this region.

PMID- 22479630
TI  - Neurochemical properties of the synapses in the pathways of orofacial nociceptive
      reflexes.
AB  - The brainstem premotor neurons of the facial nucleus (VII) and hypoglossal (XII)
      nucleus can integrate orofacial nociceptive input from the caudal spinal
      trigeminal nucleus (Vc) and coordinate orofacial nociceptive reflex (ONR)
      responses. However, the synaptoarchitectures of the ONR pathways are still
      unknown. In the current study, we examined the distribution of GABAergic premotor
      neurons in the brainstem local ONR pathways, their connections with the Vc
      projections joining the brainstem ONR pathways and the neurochemical properties
      of these connections. Retrograde tracer fluoro-gold (FG) was injected into the
      VII or XII, and anterograde tracer biotinylated dextran amine (BDA) was injected
      into the Vc. Immunofluorescence histochemical labeling for inhibitory/excitatory
      neurotransmitters combined with BDA/FG tracing showed that GABAergic premotor
      neurons were mainly distributed bilaterally in the ponto-medullary reticular
      formation with an ipsilateral dominance. Some GABAergic premotor neurons made
      close appositions to the BDA-labeled fibers coming from the Vc, and these
      appostions were mainly distributed in the parvicellular reticular formation
      (PCRt), dorsal medullary reticular formation (MdD), and supratrigeminal nucleus
      (Vsup). We further examined the synaptic relationships between the Vc projecting
      fibers and premotor neurons in the VII or XII under the confocal laser-scanning
      microscope and electron microscope, and found that the BDA-labeled axonal
      terminals that made asymmetric synapses on premotor neurons showed vesicular
      glutamate transporter 2 (VGluT2) like immunoreactivity. These results indicate
      that the GABAergic premotor neurons receive excitatory neurotransmission from the
      Vc and may contribute to modulating the generation of the tonic ONR.

PMID- 22479631
TI  - Functional validation of hydrophobic adaptation to physiological temperature in
      the small heat shock protein alphaA-crystallin.
AB  - Small heat shock proteins (sHsps) maintain cellular homeostasis by preventing
      stress and disease-induced protein aggregation. While it is known that
      hydrophobicity impacts the ability of sHsps to bind aggregation-prone denaturing
      proteins, the complex quaternary structure of globular sHsps has made
      understanding the significance of specific changes in hydrophobicity difficult.
      Here we used recombinant protein of the lenticular sHsp alpha A-crystallin from
      six teleost fishes environmentally adapted to temperatures ranging from -2
      degrees C to 40 degrees C to identify correlations between physiological
      temperature, protein stability and chaperone-like activity. Using sequence and
      structural modeling analysis we identified specific amino acid differences
      between the warm adapted zebrafish and cold adapted Antarctic toothfish that
      could contribute to these correlations and validated the functional consequences
      of three specific hydrophobicity-altering amino acid substitutions in alphaA
      crystallin. Site directed mutagenesis of three residues in the zebrafish (V62T,
      C143S, T147V) confirmed that each impacts either protein stability or chaperone
      like activity or both, with the V62T substitution having the greatest impact. Our
      results indicate a role for changing hydrophobicity in the thermal adaptation of
      alpha A-crystallin and suggest ways to produce sHsp variants with altered
      chaperone-like activity. These data also demonstrate that a comparative approach
      can provide new information about sHsp function and evolution.

PMID- 22479632
TI  - Analysis of protein interactions at native chloroplast membranes by ellipsometry.
AB  - Membrane bound receptors play vital roles in cell signaling, and are the target
      for many drugs, yet their interactions with ligands are difficult to study by
      conventional techniques due to the technical difficulty of monitoring these
      interactions in lipid environments. In particular, the ability to analyse the
      behaviour of membrane proteins in their native membrane environment is limited.
      Here, we have developed a quantitative approach to detect specific interactions
      between low-abundance chaperone receptors within native chloroplast membranes and
      their soluble chaperone partners. Langmuir-Schaefer film deposition was used to
      deposit native chloroplasts onto gold-coated glass slides, and interactions
      between the molecular chaperones Hsp70 and Hsp90 and their receptors in the
      chloroplast membranes were detected and quantified by total internal reflection
      ellipsometry (TIRE). We show that native chloroplast membranes deposited on gold
      coated glass slides using Langmuir-Schaefer films retain functional receptors
      capable of binding chaperones with high specificity and affinity. Taking into
      account the low chaperone receptor abundance in native membranes, these binding
      properties are consistent with data generated using soluble forms of the
      chloroplast chaperone receptors, OEP61 and Toc64. Therefore, we conclude that
      chloroplasts have the capacity to selectively bind chaperones, consistent with
      the notion that chaperones play an important role in protein targeting to
      chloroplasts. Importantly, this method of monitoring by TIRE does not require any
      protein labelling. This novel combination of techniques should be applicable to a
      wide variety of membranes and membrane protein receptors, thus presenting the
      opportunity to quantify protein interactions involved in fundamental cellular
      processes, and to screen for drugs that target membrane proteins.

PMID- 22479633
TI  - Threatened reef corals of the world.
AB  - A substantial proportion of the world's living species, including one-third of
      the reef-building corals, are threatened with extinction and in pressing need of
      conservation action. In order to reduce biodiversity loss, it is important to
      consider species' contribution to evolutionary diversity along with their risk of
      extinction for the purpose of setting conservation priorities. Here I reconstruct
      the most comprehensive tree of life for the order Scleractinia (1,293 species)
      that includes all 837 living reef species, and employ a composite measure of
      phylogenetic distinctiveness and extinction risk to identify the most endangered
      lineages that would not be given top priority on the basis of risk alone. The
      preservation of these lineages, not just the threatened species, is vital for
      safeguarding evolutionary diversity. Tests for phylogeny-associated patterns show
      that corals facing elevated extinction risk are not clustered on the tree, but
      species that are susceptible, resistant or resilient to impacts such as bleaching
      and disease tend to be close relatives. Intensification of these threats or
      extirpation of the endangered lineages could therefore result in disproportionate
      pruning of the coral tree of life.

PMID- 22479634
TI  - Thermal variability increases the impact of autumnal warming and drives metabolic
      depression in an overwintering butterfly.
AB  - Increases in thermal variability elevate metabolic rate due to Jensen's
      inequality, and increased metabolic rate decreases the fitness of dormant
      ectotherms by increasing consumption of stored energy reserves. Theory predicts
      that ectotherms should respond to increased thermal variability by lowering the
      thermal sensitivity of metabolism, which will reduce the impact of the warm
      portion of thermal variability. We examined the thermal sensitivity of metabolic
      rate of overwintering Erynnis propertius (Lepidoptera: Hesperiidae) larvae from a
      stable or variable environment reared in the laboratory in a reciprocal common
      garden design, and used these data to model energy use during the winters of 1973
      2010 using meteorological data to predict the energetic outcomes of metabolic
      compensation and phenological shifts. Larvae that experienced variable
      temperatures had decreased thermal sensitivity of metabolic rate, and were larger
      than those reared at stable temperatures, which could partially compensate for
      the increased energetic demands. Even with depressed thermal sensitivity, the
      variable environment was more energy-demanding than the stable, with the majority
      of this demand occurring in autumn. Autumn phenology changes thus had
      disproportionate influence on energy consumption in variable environments, and
      variable-reared larvae were most susceptible to overwinter energy drain.
      Therefore the energetic impacts of the timing of entry into winter dormancy will
      strongly influence ectotherm fitness in northern temperate environments. We
      conclude that thermal variability drives the expression of metabolic suppression
      in this species; that phenological shifts will have a greater impact on
      ectotherms in variable thermal environments; and that E. propertius will be more
      sensitive to shifts in phenology in autumn than in spring. This suggests that
      increases in overwinter thermal variability and/or extended, warm autumns, will
      negatively impact all non-feeding dormant ectotherms which lack the ability to
      suppress their overwinter metabolic thermal sensitivity.

PMID- 22479635
TI  - Nitric oxide-driven hypoxia initiates synovial angiogenesis, hyperplasia and
      inflammatory lesions in mice.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory articular disease with
      cartilage and bone damage due to hyperplasic synoviocyte invasion and subsequent
      matrix protease digestion. Although monoclonal antibodies against tumor necrosis
      factor alpha (TNFalpha) have been approved for clinical use in patients with RA,
      desired therapeutic regimens suitable for non-responders are still unavailable
      because etiological initiators leading to RA remain enigmatic and unidentified.
      METHODOLOGY/PRINCIPAL FINDINGS: Bacteria-induced arthritis (BIA) that simulates
      collagen-induced arthritis (CIA) is developed in mice upon daily live bacterial
      feeding. The morphological lesions of paw erythema and edema together with the
      histological alterations of synovial hyperplasia and lymphocytic infiltration
      emerge as the early-phase manifestations of BIA and CIA. Bacteria- or collagen
      mediated global upregulation of pro-inflammatory cytokines is accompanied by the
      burst of nitric oxide (NO). Elevation of the serum NO level is correlated with
      decline of the blood oxygen saturation percentage (SpO2), reflecting a hypoxic
      consequence during development towards arthritis. NO-driven hypoxia is further
      evident from a positive relationship between NO and lactic acid (LA), an end
      product from glycolysis. Upregulation of hypoxia inducible factor 1 alpha (HIF
      1alpha) and vascular endothelial growth factor (VEGF) validates hypoxia-induced
      angiogenesis in the inflamed synovium of modeling mice. Administration of the NO
      donor compound sodium nitroprusside (SNP) causes articular inflammation by
      inducing synovial hypoxia. Anti-bacteria by the antibiotic cefotaxime and/or the
      immunosuppressant rapamycin or artesunate that also inhibits nitric oxide
      synthase (NOS) can abrogate NO production, mitigate hypoxia, and considerably
      ameliorate or even completely abort synovitis, hence highlighting that NO may
      serve as an initiator of inflammatory arthritis. CONCLUSIONS/SIGNIFICANCE: Like
      collagen, bacteria also enable synovial lesions via upregulating pro-inflammatory
      cytokines, triggering NO production, driving hypoxic responses, and inducing
      synovial angiogenesis and hyperplasia, suggesting that sustained infection might
      be, in part, responsible for the onset of synovitis and arthritis in mice.

PMID- 22479636
TI  - First large-scale DNA barcoding assessment of reptiles in the biodiversity
      hotspot of Madagascar, based on newly designed COI primers.
AB  - BACKGROUND: DNA barcoding of non-avian reptiles based on the cytochrome oxidase
      subunit I (COI) gene is still in a very early stage, mainly due to technical
      problems. Using a newly developed set of reptile-specific primers for COI we
      present the first comprehensive study targeting the entire reptile fauna of the
      fourth-largest island in the world, the biodiversity hotspot of Madagascar.
      METHODOLOGY/PRINCIPAL FINDINGS: Representatives of the majority of Madagascan non
      avian reptile species (including Squamata and Testudines) were sampled and
      successfully DNA barcoded. The new primer pair achieved a constantly high success
      rate (72.7-100%) for most squamates. More than 250 species of reptiles (out of
      the 393 described ones; representing around 64% of the known diversity of
      species) were barcoded. The average interspecific genetic distance within
      families ranged from a low of 13.4% in the Boidae to a high of 29.8% in the
      Gekkonidae. Using the average genetic divergence between sister species as a
      threshold, 41-48 new candidate (undescribed) species were identified. Simulations
      were used to evaluate the performance of DNA barcoding as a function of
      completeness of taxon sampling and fragment length. Compared with available multi
      gene phylogenies, DNA barcoding correctly assigned most samples to species, genus
      and family with high confidence and the analysis of fewer taxa resulted in an
      increased number of well supported lineages. Shorter marker-lengths generally
      decreased the number of well supported nodes, but even mini-barcodes of 100 bp
      correctly assigned many samples to genus and family. CONCLUSIONS/SIGNIFICANCE:
      The new protocols might help to promote DNA barcoding of reptiles and the
      established library of reference DNA barcodes will facilitate the molecular
      identification of Madagascan reptiles. Our results might be useful to easily
      recognize undescribed diversity (i.e. novel taxa), to resolve taxonomic problems,
      and to monitor the international pet trade without specialized expert knowledge.

PMID- 22479637
TI  - IFITM proteins restrict antibody-dependent enhancement of dengue virus infection.
AB  - Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes
      of several pathogenic viruses, including the flaviviruses West Nile virus and
      dengue virus (DENV). DENV infects cells directly or via antibody-dependent
      enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute
      to severe disease in a secondary infection. Here we investigated whether ADE
      mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM
      proteins can be protective in a secondary infection. We observed that IFITM
      proteins restricted ADE-mediated and direct infection with comparable
      efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM
      proteins can contribute to control of secondary DENV infections.

PMID- 22479638
TI  - Network analysis of epidermal growth factor signaling using integrated genomic,
      proteomic and phosphorylation data.
AB  - To understand how integration of multiple data types can help decipher cellular
      responses at the systems level, we analyzed the mitogenic response of human
      mammary epithelial cells to epidermal growth factor (EGF) using whole genome
      microarrays, mass spectrometry-based proteomics and large-scale western blots
      with over 1000 antibodies. A time course analysis revealed significant
      differences in the expression of 3172 genes and 596 proteins, including protein
      phosphorylation changes measured by western blot. Integration of these disparate
      data types showed that each contributed qualitatively different components to the
      observed cell response to EGF and that varying degrees of concordance in gene
      expression and protein abundance measurements could be linked to specific
      biological processes. Networks inferred from individual data types were
      relatively limited, whereas networks derived from the integrated data
      recapitulated the known major cellular responses to EGF and exhibited more highly
      connected signaling nodes than networks derived from any individual dataset.
      While cell cycle regulatory pathways were altered as anticipated, we found the
      most robust response to mitogenic concentrations of EGF was induction of matrix
      metalloprotease cascades, highlighting the importance of the EGFR system as a
      regulator of the extracellular environment. These results demonstrate the value
      of integrating multiple levels of biological information to more accurately
      reconstruct networks of cellular response.

PMID- 22479639
TI  - HIV-1 Nef enhances dendritic cell-mediated viral transmission to CD4+ T cells and
      promotes T-cell activation.
AB  - HIV-1 Nef enhances dendritic cell (DC)-mediated viral transmission to CD4(+) T
      cells, but the underlying mechanism is not fully understood. It is also unknown
      whether HIV-1 infected DCs play a role in activating CD4(+) T cells and enhancing
      DC-mediated viral transmission. Here we investigated the role of HIV-1 Nef in DC
      mediated viral transmission and HIV-1 infection of primary CD4(+) T cells using
      wild-type HIV-1 and Nef-mutated viruses. We show that HIV-1 Nef facilitated DC
      mediated viral transmission to activated CD4(+) T cells. HIV-1 expressing wild
      type Nef enhanced the activation and proliferation of primary resting CD4(+) T
      cells. However, when co-cultured with HIV-1-infected autologous DCs, there was no
      significant trend for infection- or Nef-dependent proliferation of resting CD4(+)
      T cells. Our results suggest an important role of Nef in DC-mediated transmission
      of HIV-1 to activated CD4(+) T cells and in the activation and proliferation of
      resting CD4(+) T cells, which likely contribute to viral pathogenesis.

PMID- 22479640
TI  - Identification of Lygus hesperus by DNA barcoding reveals insignificant levels of
      genetic structure among distant and habitat diverse populations.
AB  - BACKGROUND: The western tarnished plant bug Lygus hesperus is an economically
      important pest that belongs to a complex of morphologically similar species that
      makes identification problematic. The present study provides evidence for the use
      of DNA barcodes from populations of L. hesperus from the western United States of
      America for accurate identification. METHODOLOGY/PRINCIPAL FINDINGS: This study
      reports DNA barcodes for 134 individuals of the western tarnished plant bug from
      alfalfa and strawberry agricultural fields in the western United States of
      America. Sequence divergence estimates of <3% reveal that morphologically
      variable individuals presumed to be L. hesperus were accurately identified.
      Paired estimates of F(st) and subsequent estimates of gene flow show that
      geographically distinct populations of L. hesperus are genetically similar.
      Therefore, our results support and reinforce the relatively recent (<100 years)
      migration of the western tarnished plant bug into agricultural habitats across
      the western United States. CONCLUSIONS/SIGNIFICANCE: This study reveals that
      despite wide host plant usage and phenotypically plastic morphological traits,
      the commonly recognized western tarnished plant bug belongs to a single species,
      Lygus hesperus. In addition, no significant genetic structure was found for the
      geographically diverse populations of western tarnished plant bug used in this
      study.

PMID- 22479641
TI  - Evolutionary dynamics analysis of human metapneumovirus subtype A2: genetic
      evidence for its dominant epidemic.
AB  - Human metapneumovirus (hMPV) is a respiratory viral pathogen in children
      worldwide. hMPV is divided into four subtypes: hMPV_A1, hMPV_A2, hMPV_B1, and
      hMPV_B2. hMPV_A2 can be further divided into hMPV_A2a and A2b based on
      phylogenetic analysis. The typical prevalence pattern of hMPV involves a shift of
      the predominant subtype within one or two years. However, hMPV_A2, in particular
      hMPV_A2b, has circulated worldwide with a several years long term high epidemic.
      To study this distinct epidemic behavior of hMPV_A2, we analyzed 294 sequences of
      partial G genes of the virus from different countries. Molecular evolutionary
      data indicates that hMPV_A2 evolved toward heterogeneity faster than the other
      subtypes. Specifically, a bayesian skyline plot analysis revealed that hMPV_A2
      has undergone a generally upward fluctuation since 1997, whereas the other
      subtypes experienced only one upward fluctuation. Although hMPV_A2 showed a lower
      value of mean dN/dS than the other subtypes, it had the largest number of
      positive selection sites. Meanwhile, various styles of mutation were observed in
      the mutation hotspots of hMPV_A2b. Bayesian phylogeography analysis also revealed
      two fusions of diffusion routes of hMPV_A2b in India (June 2006) and Beijing,
      China (June 2008). Sequences of hMPV_A2b retrieved from GenBank boosted
      simultaneously with the two fusions respectively, indicating that fusion of
      genetic transmission routes from different regions improved survival of hMPV_A2.
      Epidemic and evolutionary dynamics of hMPV_A2b were similar to those of hMPV_A2.
      Overall, our findings provide important molecular insights into hMPV epidemics
      and viral variation, and explain the occurrence of an atypical epidemic of
      hMPV_A2, particularly hMPV_A2b.

PMID- 22479642
TI  - Oxygen levels do not determine radiation survival of breast cancer stem cells.
AB  - For more than a century oxygen has been known to be one of the most powerful
      radiosensitizers. However, despite decades of preclinical and clinical research
      aimed at overcoming tumor hypoxia, little clinical progress has been made so far.
      Ionizing radiation damages DNA through generation of free radicals. In the
      presence of oxygen these lesions are chemically modified, and thus harder to
      repair while hypoxia protects cells from radiation (Oxygen enhancement ratio
      (OER)). Breast cancer stem cells (BSCSs) are protected from radiation by high
      levels of free radical scavengers even in the presence of oxygen. This led us to
      hypothesize that BCSCs exhibit an OER of 1. Using four established breast cancer
      cell lines (MCF-7, T47D, MDA-MB-231, SUM159PT) and primary breast cancer samples,
      we determined the number of BCSCs using cancer stem cell markers (ALDH1, low
      proteasome activity), compared radiation clonogenic survival and mammosphere
      formation under normoxic and hypoxic conditions, and correlated these results to
      the expression levels of key members of the free radical scavenging systems. The
      number of BCSCs increased with increased aggressiveness of the cancer. This
      correlated with increased radioresistance (SF(8Gy)), and decreasing OERs. When
      cultured as mammospheres, breast cancer cell lines and primary samples were
      highly radioresistant and not further protected by hypoxia (OER~1).We conclude
      that because BCSCs are protected from radiation through high expression levels of
      free radical scavengers, hypoxia does not lead to additional radioprotection of
      BCSCs.

PMID- 22479643
TI  - Integrated analyses of microRNAs demonstrate their widespread influence on gene
      expression in high-grade serous ovarian carcinoma.
AB  - BACKGROUND: The Cancer Genome Atlas (TCGA) Network recently comprehensively
      catalogued the molecular aberrations in 487 high-grade serous ovarian cancers,
      with much remaining to be elucidated regarding the microRNAs (miRNAs). Here,
      using TCGA ovarian data, we surveyed the miRNAs, in the context of their
      predicted gene targets. METHODS AND RESULTS: Integration of miRNA and gene
      patterns yielded evidence that proximal pairs of miRNAs are processed from
      polycistronic primary transcripts, and that intronic miRNAs and their host gene
      mRNAs derive from common transcripts. Patterns of miRNA expression revealed
      multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient
      survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression
      across tumors showed a higher frequency of in silico predicted target sites in
      the mRNA 3'-untranslated region (with less frequency observed for coding sequence
      and 5'-untranslated regions). The miR-29 family and predicted target genes were
      among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR
      29a in vitro repressed several anti-correlated genes (including DNMT3A and
      DNMT3B) and substantially decreased ovarian cancer cell viability. CONCLUSIONS:
      This study establishes miRNAs as having a widespread impact on gene expression
      programs in ovarian cancer, further strengthening our understanding of miRNA
      biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit
      high diversity reflecting the genomic heterogeneity within a clinically
      homogeneous disease population. Putative miRNA:mRNA interactions, as identified
      using integrative analysis, can be validated. TCGA data are a valuable resource
      for the identification of novel tumor suppressive miRNAs in ovarian as well as
      other cancers.

PMID- 22479644
TI  - Phenotypic and functional properties of Helios+ regulatory T cells.
AB  - Helios, an Ikaros family transcription factor, is preferentially expressed at the
      mRNA and protein level in regulatory T cells. Helios expression previously
      appeared to be restricted to thymic-derived Treg. Consistent with recent data, we
      show here that Helios expression is inducible in vitro under certain conditions.
      To understand phenotypic and functional differences between Helios(+) and Helios(
      ) Treg, we profiled cell-surface markers of FoxP3(+) Treg using unmanipulated
      splenocytes. We found that CD103 and GITR are expressed at high levels on a
      subset of Helios(+) Treg and that a Helios(+) Treg population could be
      significantly enriched by FACS sorting using these two markers. Quantitative real
      time PCR (qPCR) analysis revealed increased TGF-beta message in Helios(+) Treg,
      consistent with the possibility that this population possesses enhanced
      regulatory potential. In tumor-bearing mice, we found that Helios(+) Treg were
      relatively over-represented in the tumor-mass, and BrdU studies showed that, in
      vivo, Helios(+) Treg proliferated more than Helios(-) Treg. We hypothesized that
      Helios-enriched Treg might exert increased suppressive effects. Using in vitro
      suppression assays, we show that Treg function correlates with the absolute
      number of Helios(+) cells in culture. Taken together, these data show that
      Helios(+) Treg represent a functional subset with associated CD103 and GITR
      expression.

PMID- 22479645
TI  - Stromal interferon-gamma signaling and cross-presentation are required to
      eliminate antigen-loss variants of B cell lymphomas in mice.
AB  - To study mechanisms of T cell-mediated rejection of B cell lymphomas, we
      developed a murine lymphoma model wherein three potential rejection antigens,
      human c-MYC, chicken ovalbumin (OVA), and GFP are expressed. After transfer into
      wild-type mice 60-70% of systemically growing lymphomas expressing all three
      antigens were rejected; lymphomas expressing only human c-MYC protein were not
      rejected. OVA expressing lymphomas were infiltrated by T cells, showed MHC class
      I and II upregulation, and lost antigen expression, indicating immune escape. In
      contrast to wild-type recipients, 80-100% of STAT1-, IFN-gamma-, or IFN-gamma
      receptor-deficient recipients died of lymphoma, indicating that host IFN-gamma
      signaling is critical for rejection. Lymphomas arising in IFN-gamma- and IFN
      gamma-receptor-deficient mice had invariably lost antigen expression, suggesting
      that poor overall survival of these recipients was due to inefficient elimination
      of antigen-negative lymphoma variants. Antigen-dependent eradication of lymphoma
      cells in wild-type animals was dependent on cross-presentation of antigen by
      cells of the tumor stroma. These findings provide first evidence for an important
      role of the tumor stroma in T cell-mediated control of hematologic neoplasias and
      highlight the importance of incorporating stroma-targeting strategies into future
      immunotherapeutic approaches.

PMID- 22479646
TI  - Could a B-1 cell derived phagocyte "be one" of the peritoneal macrophages during
      LPS-driven inflammation?
AB  - The inflammatory response is driven by signals that recruit and elicit immune
      cells to areas of tissue damage or infection. The concept of a mononuclear
      phagocyte system postulates that monocytes circulating in the bloodstream are
      recruited to inflamed tissues where they give rise to macrophages. A recent
      publication demonstrated that the large increase in the macrophages observed
      during infection was the result of the multiplication of these cells rather than
      the recruitment of blood monocytes. We demonstrated previously that B-1 cells
      undergo differentiation to acquire a mononuclear phagocyte phenotype in vitro (B
      1CDP), and we propose that B-1 cells could be an alternative origin for
      peritoneal macrophages. A number of recent studies that describe the phagocytic
      and microbicidal activity of B-1 cells in vitro and in vivo support this
      hypothesis. Based on these findings, we further investigated the differentiation
      of B-1 cells into phagocytes in vivo in response to LPS-induced inflammation.
      Therefore, we investigated the role of B-1 cells in the composition of the
      peritoneal macrophage population after LPS stimulation using osteopetrotic mice,
      BALB/Xid mice and the depletion of monocytes/macrophages by clodronate treatment.
      We show that peritoneal macrophages appear in op/op((-/-)) mice after LPS
      stimulation and exhibit the same Ig gene rearrangement (VH11) that is often found
      in B-1 cells. These results strongly suggest that op/op((-/-)) peritoneal
      "macrophages" are B-1CDP. Similarly, the LPS-induced increase in the macrophage
      population was observed even following monocyte/macrophage depletion by
      clodronate. After monocyte/macrophage depletion by clodronate, LPS-elicited
      macrophages were observed in BALB/Xid mice only following the transfer of B-1
      cells. Based on these data, we confirmed that B-1 cell differentiation into
      phagocytes also occurs in vivo. In conclusion, the results strongly suggest that
      B-1 cell derived phagocytes are a component of the LPS-elicited peritoneal
      macrophage population.

PMID- 22479647
TI  - Therapeutic benefit of radial optic neurotomy in a rat model of glaucoma.
AB  - Radial optic neurotomy (RON) has been proposed as a surgical treatment to
      alleviate the neurovascular compression and to improve the venous outflow in
      patients with central retinal vein occlusion. Glaucoma is characterized by
      specific visual field defects due to the loss of retinal ganglion cells and
      damage to the optic nerve head (ONH). One of the clinical hallmarks of
      glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to
      analyze the effect of RON in an experimental model of glaucoma in rats induced by
      intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar
      rats were bilaterally injected with vehicle or CS in the eye anterior chamber,
      once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON
      was performed by a single incision in the edge of the neuro-retinal ring at the
      nasal hemisphere of the optic disk in one eye, while the contralateral eye was
      submitted to a sham procedure. Electroretinograms (ERGs) were registered under
      scotopic conditions and visual evoked potentials (VEPs) were registered with
      skull-implanted electrodes. Retinal and optic nerve morphology was examined by
      optical microscopy. RON did not affect the ocular hypertension induced by CS. In
      eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave
      amplitude) and visual pathway (VEP N2-P2 component amplitude) function was
      observed, whereas RON reduced these functional alterations in hypertensive eyes.
      Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-,
      NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas
      RON significantly preserved these parameters. In addition, RON preserved the
      optic nerve structure in eyes with chronic ocular hypertension. These results
      indicate that RON reduces functional and histological alterations induced by
      experimental chronic ocular hypertension.

PMID- 22479648
TI  - Proteasome inhibitor bortezomib ameliorates intestinal injury in mice.
AB  - BACKGROUND: Bortezomib is a proteasome inhibitor that has shown impressive
      efficacy in the treatment of multiple myeloma. In mice, the addition of dextran
      sulfate sodium (DSS) to drinking water leads to acute colitis that can serve as
      an experimental animal model for human ulcerative colitis. METHODOLOGY/PRINCIPAL
      FINDINGS: Bortezomib treatment was shown to potently inhibit murine DSS-induced
      colitis. The attenuation of DSS-induced colitis was associated with decreased
      inflammatory cell infiltration in the colon. Specifically, bortezomib-treated
      mice showed significantly decreased numbers of CD4(+) and CD8(+) T cells in the
      colon and mesenteric lymph nodes. Bortezomib treatment significantly diminished
      interferon (IFN)-gamma expression in the colon and mesenteric lymph nodes.
      Furthermore, cytoplasmic IFN-gamma production by CD4(+) and CD8(+) T cells in
      mesenteric lymph nodes was substantially decreased by bortezomib treatment.
      Notably, bortezomib enhanced T cell apoptosis by inhibiting nuclear factor-kappaB
      activation during DSS-induced colitis. CONCLUSIONS/SIGNIFICANCE: Bortezomib
      treatment is likely to induce T cell death, thereby suppressing DSS-induced
      colitis by reducing IFN-gamma production.

PMID- 22479649
TI  - Heterogeneity of inflammatory and cytokine networks in chronic plaque psoriasis.
AB  - The clinical features of psoriasis, characterized by sharply demarcated scaly
      erythematous plaques, are typically so distinctive that a diagnosis can easily be
      made on these grounds alone. However, there is great variability in treatment
      response between individual patients, and this may reflect heterogeneity of
      inflammatory networks driving the disease. In this study, whole-genome
      transcriptional profiling was used to characterize inflammatory and cytokine
      networks in 62 lesional skin samples obtained from patients with stable chronic
      plaque psoriasis. We were able to stratify lesions according to their
      inflammatory gene expression signatures, identifying those associated with strong
      (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%).
      Additionally, we identified differences in cytokine signatures with heightened
      cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and
      attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub
      groups correlated with the composition of the inflammatory infiltrate, but were
      only weakly associated with increased risk allele frequency at some psoriasis
      susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight
      variable points in the inflammatory and cytokine networks known to drive chronic
      plaque psoriasis. Such heterogeneous aspects may shape clinical course and
      treatment responses, and can provide avenues for development of personalized
      treatments.

PMID- 22479650
TI  - Increased resin collection after parasite challenge: a case of self-medication in
      honey bees?
AB  - The constant pressure posed by parasites has caused species throughout the animal
      kingdom to evolve suites of mechanisms to resist infection. Individual barriers
      and physiological defenses are considered the main barriers against parasites in
      invertebrate species. However, behavioral traits and other non-immunological
      defenses can also effectively reduce parasite transmission and infection
      intensity. In social insects, behaviors that reduce colony-level parasite loads
      are termed "social immunity." One example of a behavioral defense is resin
      collection. Honey bees forage for plant-produced resins and incorporate them into
      their nest architecture. This use of resins can reduce chronic elevation of an
      individual bee's immune response. Since high activation of individual immunity
      can impose colony-level fitness costs, collection of resins may benefit both the
      individual and colony fitness. However the use of resins as a more direct defense
      against pathogens is unclear. Here we present evidence that honey bee colonies
      may self-medicate with plant resins in response to a fungal infection. Self
      medication is generally defined as an individual responding to infection by
      ingesting or harvesting non-nutritive compounds or plant materials. Our results
      show that colonies increase resin foraging rates after a challenge with a fungal
      parasite (Ascophaera apis: chalkbrood or CB). Additionally, colonies
      experimentally enriched with resin had decreased infection intensities of this
      fungal parasite. If considered self-medication, this is a particularly unique
      example because it operates at the colony level. Most instances of self
      medication involve pharmacophagy, whereby individuals change their diet in
      response to direct infection with a parasite. In this case with honey bees,
      resins are not ingested but used within the hive by adult bees exposed to fungal
      spores. Thus the colony, as the unit of selection, may be responding to infection
      through self-medication by increasing the number of individuals that forage for
      resin.

PMID- 22479651
TI  - Cdt1 is differentially targeted for degradation by anticancer chemotherapeutic
      drugs.
AB  - BACKGROUND: Maintenance of genome integrity is crucial for the propagation of the
      genetic information. Cdt1 is a major component of the pre-replicative complex,
      which controls once per cell cycle DNA replication. Upon DNA damage, Cdt1 is
      rapidly targeted for degradation. This targeting has been suggested to safeguard
      genomic integrity and prevent re-replication while DNA repair is in progress.
      Cdt1 is deregulated in tumor specimens, while its aberrant expression is linked
      with aneuploidy and promotes tumorigenesis in animal models. The induction of
      lesions in DNA is a common mechanism by which many cytotoxic anticancer agents
      operate, leading to cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL
      FINDING: In the present study we examine the ability of several anticancer drugs
      to target Cdt1 for degradation. We show that treatment of HeLa and HepG2 cells
      with MMS, Cisplatin and Doxorubicin lead to rapid proteolysis of Cdt1, whereas
      treatment with 5-Fluorouracil and Tamoxifen leave Cdt1 expression unaffected.
      Etoposide affects Cdt1 stability in HepG2 cells and not in HeLa cells. RNAi
      experiments suggest that Cdt1 proteolysis in response to MMS depends on the
      presence of the sliding clamp PCNA. CONCLUSION/SIGNIFICANCE: Our data suggest
      that treatment of tumor cells with commonly used chemotherapeutic agents induces
      differential responses with respect to Cdt1 proteolysis. Information on specific
      cellular targets in response to distinct anticancer chemotherapeutic drugs in
      different cancer cell types may contribute to the optimization of the efficacy of
      chemotherapy.

PMID- 22479652
TI  - Group dynamics and landscape features constrain the exploration of herds in
      fusion-fission societies: the case of European roe deer.
AB  - Despite the large number of movement studies, the constraints that grouping
      imposes on movement decisions remain essentially unexplored, even for highly
      social species. Such constraints could be key, however, to understanding the
      dynamics and spatial organisation of species living in group fusion-fission
      systems. We investigated the winter movements (speed and diffusion coefficient)
      of groups of free-ranging roe deer (Capreolus capreolus), in an agricultural
      landscape characterised by a mosaic of food and foodless patches. Most groups
      were short-lived units that merged and split up frequently during the course of a
      day. Deer groups decreased their speed and diffusion rate in areas where food
      patches were abundant, as well as when travelling close to main roads and crest
      lines and far from forests. While accounting for these behavioural adjustments to
      habitat features, our study revealed some constraints imposed by group foraging:
      large groups reached the limit of their diffusion rate faster than small groups.
      The ability of individuals to move rapidly to new foraging locations following
      patch depression thus decreases with group size. Our results highlight the
      importance of considering both habitat heterogeneity and group dynamics when
      predicting the movements of individuals in group fusion-fission societies.
      Further, we provide empirical evidence that group cohesion can restrain movement
      and, therefore, the speed at which group members can explore their environment.
      When maintaining cohesion reduces foraging gains because of movement constraints,
      leaving the group may become a fitness-rewarding decision, especially when
      individuals can join other groups located nearby, which would tend to maintain
      highly dynamical group fusion-fission systems. Our findings also provide the
      basis for new hypotheses explaining a broad range of ecological patterns, such as
      the broader diet and longer residency time reported for larger herbivore groups.

PMID- 22479653
TI  - Many neglected tropical diseases may have originated in the Paleolithic or
      before: new insights from genetics.
AB  - The standard view of modern human infectious diseases is that many of them arose
      during the Neolithic when animals were first domesticated, or afterwards. Here we
      review recent genetic and molecular clock estimates that point to a much older
      Paleolithic origin (2.5 million years ago to 10,000 years ago) of some of these
      diseases. During part of this ancient period our early human ancestors were still
      isolated in Africa. We also discuss the need for investigations of the origin of
      these diseases in African primates and other animals that have been the original
      source of many neglected tropical diseases.

PMID- 22479654
TI  - Chikungunya disease: infection-associated markers from the acute to the chronic
      phase of arbovirus-induced arthralgia.
AB  - At the end of 2005, an outbreak of fever associated with joint pain occurred in
      La Reunion. The causal agent, chikungunya virus (CHIKV), has been known for 50
      years and could thus be readily identified. This arbovirus is present worldwide,
      particularly in India, but also in Europe, with new variants returning to Africa.
      In humans, it causes a disease characterized by a typical acute infection,
      sometimes followed by persistent arthralgia and myalgia lasting months or years.
      Investigations in the La Reunion cohort and studies in a macaque model of
      chikungunya implicated monocytes-macrophages in viral persistence. In this
      Review, we consider the relationship between CHIKV and the immune response and
      discuss predictive factors for chronic arthralgia and myalgia by providing an
      overview of current knowledge on chikungunya pathogenesis. Comparisons of data
      from animal models of the acute and chronic phases of infection, and data from
      clinical series, provide information about the mechanisms of CHIKV infection
      associated inflammation, viral persistence in monocytes-macrophages, and their
      link to chronic signs.

PMID- 22479655
TI  - Assessing the potential of a candidate dengue vaccine with mathematical modeling.

PMID- 22479656
TI  - Texas and Mexico: sharing a legacy of poverty and neglected tropical diseases.

PMID- 22479657
TI  - High seroprevalence of Rift Valley FEVER AND EVIDENCE FOR ENDEMIC circulation in
      Mbeya region, Tanzania, in a cross-sectional study.
AB  - BACKGROUND: The Rift Valley fever virus (RVFV) is an arthropod-borne phlebovirus.
      RVFV mostly causes outbreaks among domestic ruminants with a major economic
      impact. Human infections are associated with these events, with a fatality rate
      of 0.5-2%. Since the virus is able to use many mosquito species of temperate
      climates as vectors, it has a high potential to spread to outside Africa.
      METHODOLOGY/PRINCIPAL FINDINGS: We conducted a stratified, cross-sectional sero
      prevalence survey in 1228 participants from Mbeya region, southwestern Tanzania.
      Samples were selected from 17,872 persons who took part in a cohort study in 2007
      and 2008. RVFV IgG status was determined by indirect immunofluorescence. Possible
      risk factors were analyzed using uni- and multi-variable Poisson regression
      models. We found a unique local maximum of RVFV IgG prevalence of 29.3% in a
      study site close to Lake Malawi (N = 150). The overall seroprevalence was 5.2%.
      Seropositivity was significantly associated with higher age, lower socio-economic
      status, ownership of cattle and decreased with distance to Lake Malawi. A high
      vegetation density, higher minimum and lower maximum temperatures were found to
      be associated with RVFV IgG positivity. Altitude of residence, especially on a
      small scale in the high-prevalence area was strongly correlated (PR 0.87 per
      meter, 95% CI = 0.80-0.94). Abundant surface water collections are present in the
      lower areas of the high-prevalence site. RVF has not been diagnosed clinically,
      nor an outbreak detected in the high-prevalence area. CONCLUSIONS: RVFV is
      probably circulating endemically in the region. The presence of cattle, dense
      vegetation and temperate conditions favour mosquito propagation and virus
      replication in the vector and seem to play major roles in virus transmission and
      circulation. The environmental risk-factors that we identified could serve to
      more exactly determine areas at risk for RVFV endemicity.

PMID- 22479658
TI  - A pilot study on developing mucosal vaccine against alveolar echinococcosis (AE)
      using recombinant tetraspanin 3: Vaccine efficacy and immunology.
AB  - BACKGROUND: We have previously evaluated the vaccine efficacies of seven
      tetraspanins of Echinococcus multilocularis (Em-TSP1-7) against alveolar
      echinococcosis (AE) by subcutaneous (s.c.) administration with Freund's adjuvant.
      Over 85% of liver cyst lesion number reductions (CLNR) were achieved by
      recombinant Em-TSP1 (rEm-TSP1) and -TSP3 (rEm-TSP3). However, to develop an
      efficient and safe human vaccine, the efficacy of TSP mucosal vaccines must be
      thoroughly evaluated. METHODOLOGY/PRINCIPAL FINDINGS: rEm-TSP1 and -TSP3 along
      with nontoxic CpG ODN (CpG oligodeoxynucleotides) adjuvant were intranasally
      (i.n.) immunized to BALB/c mice and their vaccine efficacies were evaluated by
      counting liver CLNR (experiment I). 37.1% (p < 0.05) and 62.1% (p < 0.001) of
      CLNR were achieved by these two proteins, respectively. To study the protection
      associated immune responses induced by rEm-TSP3 via different immunization routes
      (i.n. administration with CpG or s.c. immunization with Freund's adjuvant), the
      systemic and mucosal antibody responses were detected by ELISA (experiment II).
      S.c. and i.n. administration of rEm-TSP3 achieved 81.9% (p < 0.001) and 62.8% (p
      < 0.01) CLNR in the liver, respectively. Both the immunization routes evoked
      strong serum IgG, IgG1 and IgG2alpha responses; i.n. immunization induced
      significantly higher IgA responses in nasal cavity and intestine compared with
      s.c. immunization (p < 0.001). Both immunization routes induced extremely strong
      liver IgA antibody responses (p < 0.001). The Th1 and Th2 cell responses were
      assessed by examining the IgG1/IgG2alpha ratio at two and three weeks post
      immunization. S.c. immunization resulted in a reduction in the IgG1/IgG2alpha
      ratio (Th1 tendency), whereas i.n. immunization caused a shift from Th1 to Th2.
      Moreover, immunohistochemistry showed that Em-TSP1 and -TSP3 were extensively
      located on the surface of E. multilocularis cysts, protoscoleces and adult worms
      with additional expression of Em-TSP3 in the inner part of protoscoleces and
      oncospheres. CONCLUSIONS: Our study indicated that i.n. administration of rEm
      TSP3 with CpG is able to induce both systemic and local immune responses and thus
      provides significant protection against AE.

PMID- 22479660
TI  - Density-dependent mortality of the human host in onchocerciasis: relationships
      between microfilarial load and excess mortality.
AB  - BACKGROUND: The parasite Onchocerca volvulus has, until recently, been regarded
      as the cause of a chronic yet non-fatal condition. Recent analyses, however, have
      indicated that in addition to blindness, the parasite can also be directly
      associated with human mortality. Such analyses also suggested that the
      relationship between microfilarial load and excess mortality might be non-linear.
      Determining the functional form of such relationship would contribute to quantify
      the population impact of mass microfilaricidal treatment. METHODOLOGY/PRINCIPAL
      FINDINGS: Data from the Onchocerciasis Control Programme in West Africa (OCP)
      collected from 1974 through 2001 were used to determine functional relationships
      between microfilarial load and excess mortality of the human host. The goodness
      of-fit of three candidate functional forms (a (log-) linear model and two
      saturating functions) were explored and a saturating (log-) sigmoid function was
      deemed to be statistically the best fit. The excess mortality associated with
      microfilarial load was also found to be greater in younger hosts. The
      attributable mortality risk due to onchocerciasis was estimated to be 5.9%.
      CONCLUSIONS/SIGNIFICANCE: Incorporation of this non-linear functional
      relationship between microfilarial load and excess mortality into mathematical
      models for the transmission and control of onchocerciasis will have important
      implications for our understanding of the population biology of O. volvulus, its
      impact on human populations, the global burden of disease due to onchocerciasis,
      and the projected benefits of control programmes in both human and economic
      terms.

PMID- 22479661
TI  - Sensitive and specific target sequences selected from retrotransposons of
      Schistosoma japonicum for the diagnosis of schistosomiasis.
AB  - BACKGROUND: Schistosomiasis japonica is a serious debilitating and sometimes
      fatal disease. Accurate diagnostic tests play a key role in patient management
      and control of the disease. However, currently available diagnostic methods are
      not ideal, and the detection of the parasite DNA in blood samples has turned out
      to be one of the most promising tools for the diagnosis of schistosomiasis. In
      our previous investigations, a 230-bp sequence from the highly repetitive
      retrotransposon SjR2 was identified and it showed high sensitivity and
      specificity for detecting Schistosoma japonicum DNA in the sera of rabbit model
      and patients. Recently, 29 retrotransposons were found in S. japonicum genome by
      our group. The present study highlighted the key factors for selecting a new
      perspective sensitive target DNA sequence for the diagnosis of schistosomiasis,
      which can serve as example for other parasitic pathogens. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we demonstrated that the key factors based on the
      bioinformatic analysis for selecting target sequence are the higher genome
      proportion, repetitive complete copies and partial copies, and active ESTs than
      the others in the chromosome genome. New primers based on 25 novel
      retrotransposons and SjR2 were designed and their sensitivity and specificity for
      detecting S. japonicum DNA were compared. The results showed that a new 303-bp
      sequence from non-long terminal repeat (LTR) retrotransposon (SjCHGCS19) had high
      sensitivity and specificity. The 303-bp target sequence was amplified from the
      sera of rabbit model at 3 d post-infection by nested-PCR and it became negative
      at 17 weeks post-treatment. Furthermore, the percentage sensitivity of the nested
      PCR was 97.67% in 43 serum samples of S. japonicum-infected patients.
      CONCLUSIONS/SIGNIFICANCE: Our findings highlighted the key factors based on the
      bioinformatic analysis for selecting target sequence from S. japonicum genome,
      which provide basis for establishing powerful molecular diagnostic techniques
      that can be used for monitoring early infection and therapy efficacy to support
      schistosomiasis control programs.

PMID- 22479659
TI  - Extensive genetic diversity, unique population structure and evidence of genetic
      exchange in the sexually transmitted parasite Trichomonas vaginalis.
AB  - BACKGROUND: Trichomonas vaginalis is the causative agent of human trichomoniasis,
      the most common non-viral sexually transmitted infection world-wide. Despite its
      prevalence, little is known about the genetic diversity and population structure
      of this haploid parasite due to the lack of appropriate tools. The development of
      a panel of microsatellite makers and SNPs from mining the parasite's genome
      sequence has paved the way to a global analysis of the genetic structure of the
      pathogen and association with clinical phenotypes. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we utilize a panel of T. vaginalis-specific genetic markers to
      genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea,
      Italy, Africa and the United States, including 19 clinical isolates recently
      collected from 270 women attending New York City sexually transmitted disease
      clinics. Using population genetic analysis, we show that T. vaginalis is a
      genetically diverse parasite with a unique population structure consisting of two
      types present in equal proportions world-wide. Parasites belonging to the two
      types (type 1 and type 2) differ significantly in the rate at which they harbor
      the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in
      their sensitivity to the widely-used drug, metronidazole. We also uncover
      evidence of genetic exchange, indicating a sexual life-cycle of the parasite
      despite an absence of morphologically-distinct sexual stages.
      CONCLUSIONS/SIGNIFICANCE: Our study represents the first robust and comprehensive
      evaluation of global T. vaginalis genetic diversity and population structure. Our
      identification of a unique two-type structure, and the clinically relevant
      phenotypes associated with them, provides a new dimension for understanding T.
      vaginalis pathogenesis. In addition, our demonstration of the possibility of
      genetic exchange in the parasite has important implications for genetic research
      and control of the disease.

PMID- 22479662
TI  - Membrane cholesterol regulates lysosome-plasma membrane fusion events and
      modulates Trypanosoma cruzi invasion of host cells.
AB  - BACKGROUND: Trypomastigotes of Trypanosoma cruzi are able to invade several types
      of non-phagocytic cells through a lysosomal dependent mechanism. It has been
      shown that, during invasion, parasites trigger host cell lysosome exocytosis,
      which initially occurs at the parasite-host contact site. Acid sphingomyelinase
      released from lysosomes then induces endocytosis and parasite internalization.
      Lysosomes continue to fuse with the newly formed parasitophorous vacuole until
      the parasite is completely enclosed by lysosomal membrane, a process
      indispensable for a stable infection. Previous work has shown that host membrane
      cholesterol is also important for the T. cruzi invasion process in both
      professional (macrophages) and non-professional (epithelial) phagocytic cells.
      However, the mechanism by which cholesterol-enriched microdomains participate in
      this process has remained unclear. METHODOLOGY/PRINCIPAL FINDING: In the present
      work we show that cardiomyocytes treated with MbetaCD, a drug able to sequester
      cholesterol from cell membranes, leads to a 50% reduction in invasion by T. cruzi
      trypomastigotes, as well as a decrease in the number of recently internalized
      parasites co-localizing with lysosomal markers. Cholesterol depletion from host
      membranes was accompanied by a decrease in the labeling of host membrane lipid
      rafts, as well as excessive lysosome exocytic events during the earlier stages of
      treatment. Precocious lysosomal exocytosis in MbetaCD treated cells led to a
      change in lysosomal distribution, with a reduction in the number of these
      organelles at the cell periphery, and probably compromises the intracellular pool
      of lysosomes necessary for T. cruzi invasion. CONCLUSION/SIGNIFICANCE: Based on
      these results, we propose that cholesterol depletion leads to unregulated
      exocytic events, reducing lysosome availability at the cell cortex and
      consequently compromise T. cruzi entry into host cells. The results also suggest
      that two different pools of lysosomes are available in the cell and that
      cholesterol depletion may modulate the fusion of pre-docked lysosomes at the cell
      cortex.

PMID- 22479663
TI  - A somatically diversified defense factor, FREP3, is a determinant of snail
      resistance to schistosome infection.
AB  - Schistosomiasis, a neglected tropical disease, owes its continued success to
      freshwater snails that support production of prolific numbers of human-infective
      cercariae. Encounters between schistosomes and snails do not always result in the
      snail becoming infected, in part because snails can mount immune responses that
      prevent schistosome development. Fibrinogen-related protein 3 (FREP3) has been
      previously associated with snail defense against digenetic trematode infection.
      It is a member of a large family of immune molecules with a unique structure
      consisting of one or two immunoglobulin superfamily domains connected to a
      fibrinogen domain; to date fibrinogen containing proteins with this arrangement
      are found only in gastropod molluscs. Furthermore, specific gastropod FREPs have
      been shown to undergo somatic diversification. Here we demonstrate that siRNA
      mediated knockdown of FREP3 results in a phenotypic loss of resistance to
      Schistosoma mansoni infection in 15 of 70 (21.4%) snails of the resistant BS-90
      strain of Biomphalaria glabrata. In contrast, none of the 64 control BS-90 snails
      receiving a GFP siRNA construct and then exposed to S. mansoni became infected.
      Furthermore, resistance to S. mansoni was overcome in 22 of 48 snails (46%) by
      pre-exposure to another digenetic trematode, Echinostoma paraensei. Loss of
      resistance in this case was shown by microarray analysis to be associated with
      strong down-regulation of FREP3, and other candidate immune molecules. Although
      many factors are certainly involved in snail defense from trematode infection,
      this study identifies for the first time the involvement of a specific snail
      gene, FREP3, in the phenotype of resistance to the medically important parasite,
      S. mansoni. The results have implications for revealing the underlying mechanisms
      involved in dictating the range of snail strains used by S. mansoni, and, more
      generally, for better understanding the phenomena of host specificity and host
      switching. It also highlights the role of a diversified invertebrate immune
      molecule in defense against a human pathogen. It suggests new lines of
      investigation for understanding how susceptibility of snails in areas endemic for
      S. mansoni could be manipulated and diminished.

PMID- 22479664
TI  - Taenia solium Infections in a rural area of Eastern Zambia-a community based
      study.
AB  - BACKGROUND: Taenia solium taeniosis/cysticercosis is a parasitic infection
      occurring in many developing countries. Data on the status of human infections in
      Zambia is largely lacking. We conducted a community-based study in Eastern Zambia
      to determine the prevalence of human taeniosis and cysticercosis in a rural
      community. METHODS AND FINDINGS: Stool and serum samples were collected from
      willing participants. Geographical references of the participants' households
      were determined and household questionnaires administered. Taeniosis was
      diagnosed in stool samples by coprology and by the polyclonal antibody-based
      copro-antigen enzyme-linked immunosorbent assay (copro-Ag ELISA), while
      cysticercosis was diagnosed in serum by the B158/B60 monoclonal antibody-based
      antigen ELISA (sero-Ag ELISA). Identification of the collected tapeworm after
      niclosamide treatment and purgation was done using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). A total of 255 households
      from 20 villages participated in the study, 718 stool and 708 serum samples were
      collected and examined. Forty-five faecal samples (6.3%) were found positive for
      taeniosis on copro-Ag ELISA while circulating cysticercus antigen was detected in
      5.8% (41/708) individuals. The tapeworm recovered from one of the cases was
      confirmed to be T. solium on PCR-RFLP. Seropositivity (cysticercosis) was
      significantly positively related to age (p = 0.00) and to copro-Ag positivity
      (taeniosis) (p = 0.03) but not to gender. Change point analysis revealed that the
      frequency of cysticercus antigens increased significantly in individuals above
      the age of 30. Copro-Ag positivity was not related to age or gender. The
      following risk factors were noted to be present in the study community: free
      range pig husbandry system and poor sanitation with 47.8% of the households
      visited lacking latrines. CONCLUSIONS: This study has recorded high taeniosis and
      cysticercosis prevalences and identified the need for further studies on
      transmission dynamics and impact of the disease on the local people.

PMID- 22479666
TI  - An Introduction to the Volume 3, Number 1 of Behavior Analysis in Practice (BAP).

PMID- 22479665
TI  - Pinpointing P450s associated with pyrethroid metabolism in the dengue vector,
      Aedes aegypti: developing new tools to combat insecticide resistance.
AB  - BACKGROUND: Pyrethroids are increasingly used to block the transmission of
      diseases spread by Aedes aegypti such as dengue and yellow fever. However,
      insecticide resistance poses a serious threat, thus there is an urgent need to
      identify the genes and proteins associated with pyrethroid resistance in order to
      produce effective counter measures. In Ae. aegypti, overexpression of P450s such
      as the CYP9J32 gene have been linked with pyrethroid resistance. Our aim was to
      confirm the role of CYP9J32 and other P450s in insecticide metabolism in order to
      identify potential diagnostic resistance markers. METHODOLOGY/PRINCIPAL FINDINGS:
      We have expressed CYP9J32 in Escherichia coli and show that the enzyme can
      metabolize the pyrethroids permethrin and deltamethrin. In addition, three other
      Ae. aegypti P450s (CYP9J24, CYP9J26, CYP9J28) were found capable of pyrethroid
      metabolism, albeit with lower activity. Both Ae. aegypti and Anopheles gambiae
      P450s (CYP's 6M2, 6Z2, 6P3) were screened against fluorogenic and luminescent
      substrates to identify potential diagnostic probes for P450 activity. Luciferin
      PPXE was preferentially metabolised by the three major pyrethroid metabolisers
      (CYP9J32, CYP6M2 and CYP6P3), identifying a potential diagnostic substrate for
      these P450s. CONCLUSIONS/SIGNIFICANCE: P450s have been identified with the
      potential to confer pyrethroid resistance in Ae.aegypti. It is recommended that
      over expression of these enzymes should be monitored as indicators of resistance
      where pyrethroids are used.

PMID- 22479667
TI  - Psychotropic drug treatments for people with autism and other developmental
      disorders: a primer for practicing behavior analysts.
AB  - Many people with developmental disabilities receive medications prescribed to
      improve behavior. This manuscript overviews the psychopharmacology of
      developmental disabilities and considers how practitioners can assist in
      improving the quality of the pharmacological treatments that their clients
      receive.

PMID- 22479668
TI  - Toward effective and preferred programming: a case for the objective measurement
      of social validity with recipients of behavior-change programs.
AB  - The adoption of effective behavioral interventions and teaching strategies for
      young children is largely influenced by the extent to which stakeholders find the
      procedures appropriate and the effects important. Stakeholder values have been
      described by measures of social validity in applied behavior analysis, and these
      measures have been a part of behavior-analytic research and practice since their
      important characteristics were described in the late 1970s. The typically
      subjective nature of the social validation process appears, however, to have
      marginalized children and other usual recipients of behavior-change procedures
      (i.e., individuals with autism or intellectual disabilities) from social
      validation processes. Therefore, the importance of including recipients of
      behavior-change procedures in the social validation process and methods for doing
      so are described in this paper.

PMID- 22479670
TI  - Tier II Interventions within the Framework of School-Wide Positive Behavior
      Support: Essential Features for Design, Implementation, and Maintenance.
AB  - To meet the complex social behavioral and academic needs of all students, schools
      benefit from having available multiple evidence-based interventions of varying
      intensity. School-wide positive behavior support provides a framework within
      which a continuum of evidence-based interventions can be implemented in a school.
      This framework includes three levels or tiers of intervention; Tier I (primary or
      universal), Tier II (secondary or targeted), and Tier III (tertiary or
      individualized) supports. In this paper we review the logic behind school-wide
      positive behavior support and then focus on Tier II interventions, as this level
      of support has received the least attention in the literature. We delineate the
      key features of Tier II interventions as implemented within school-wide positive
      behavior support, provide guidelines for matching Tier II interventions to school
      and student needs, and describe how schools plan for implementation and
      maintenance of selected interventions.

PMID- 22479669
TI  - Function-based treatments for escape-maintained problem behavior: a treatment
      selection model for practicing behavior analysts.
AB  - Escape from instructional activities is a common maintaining variable for problem
      behavior and a number of effective treatments have been developed for this
      function. Each of these treatments has characteristics that make them optimal for
      certain environments and clients, but less optimal for others. We summarize the
      most commonly researched function-based treatments for escape-maintained
      behavior, describe the contexts for which they are most appropriate, and provide
      a clinical model for selecting treatments based on client characteristics and the
      constraints of the therapeutic environment.

PMID- 22479671
TI  - What Every Behavior Analyst Should Know About the "MMR Causes Autism" Hypothesis.
AB  - In 1998, the English physician Andrew Wakefield suggested that the MMR vaccine
      insults the guts of children who then regress developmentally and become
      autistic. Although his research did not provide firm evidence for this
      hypothesis, many believe that (a) the MMR vaccine can cause autism; (b) children
      with autism typically have gastrointestinal problems; and, (c) a necessary
      component of treating autism is "treating the gut" through dietary restrictions.
      Research has subsequently shown that Wakefield's hypothesis is unquestionably
      false, children with autism are not more likely to have gastrointestinal
      problems, and there is no sound evidence that diets are a valid treatment for
      autism. This paper will critically review these topics.

PMID- 22479672
TI  - Identification of Stylosanthes guianensis varieties using molecular genetic
      analysis.
AB  - BACKGROUND AND AIMS: The botanical classification of Stylosanthes guianensis is
      controversial, and few studies have used molecular markers to analyse this
      species. We used microsatellite markers to study the genetic diversity and
      population structure of S. guianensis and compare our results with the current
      infraspecific botanical classification. METHODOLOGY: A representative sample from
      the S. guianensis Brazilian germplasm collection (150 accessions) was analysed
      using 20 microsatellite loci. A model-based Bayesian approach implemented in the
      software STRUCTURE was used to assign accessions into clusters. A dendrogram was
      constructed based on Roger's genetic distances. PRINCIPAL RESULTS: The number of
      alleles per locus varied from 2 to 11, with an average of 4.7. The observed
      (H(O)) and expected (H(E)) heterozygosity values varied from 0 to 0.58 (mean of
      0.18) and from 0.04 to 0.83 (mean of 0.55), respectively. Nine groups were
      assembled in STRUCTURE, and these groups were consistent with clusters inferred
      from the genetic distances and taxonomic varieties described for S. guianensis.
      The G(ST) among the nine groups was 0.46. CONCLUSIONS: The low H(O) and the G(ST)
      values observed are in agreement with the outcrossing rate (26 %) estimated for
      this species. The data indicate a high genetic diversity among and within the
      botanical varieties and suggest that microsatellite-based information can be
      combined with classical taxonomy to elucidate infraspecific levels.

PMID- 22479673
TI  - Cytogenetic characterization and genome size of the medicinal plant Catharanthus
      roseus (L.) G. Don.
AB  - BACKGROUND AND AIMS: Catharanthus roseus is a highly valuable medicinal plant
      producing several terpenoid indole alkaloids (TIAs) with pharmaceutical
      applications, including the anticancer agents vinblastine and vincristine. Due to
      the interest in its TIAs, C. roseus is one of the most extensively studied
      medicinal plants and has become a model species for the study of plant secondary
      metabolism. However, very little is known about the cytogenetics and genome size
      of this species, in spite of their importance for breeding programmes, TIA
      genetics and emerging genomic research. Therefore, the present paper provides a
      karyotype description and fluorescence in situ hybridization (FISH) data for C.
      roseus, as well as a rigorous characterization of its genome size. METHODOLOGY:
      The organization of C. roseus chromosomes was characterized using several
      DNA/chromatin staining techniques and FISH of rDNA. Genome size was investigated
      by flow cytometry using an optimized methodology. PRINCIPAL RESULTS: The C.
      roseus full chromosome complement of 2n = 16 includes two metacentric, four
      subtelocentric and two telocentric chromosome pairs, with the presence of a
      single nucleolus organizer region in chromosome 6. An easy and reliable flow
      cytometry protocol for nuclear genome analysis of C. roseus was optimized, and
      the C-value of this species was estimated to be 1C = 0.76 pg, corresponding to
      738 Mbp. CONCLUSIONS: The organization and size of the C. roseus genome were
      characterized, providing an important basis for future studies of this important
      medicinal species, including further cytogenetic mapping, genomics, TIA genetics
      and breeding programmes.

PMID- 22479674
TI  - An epifluorescent attachment improves whole-plant digital photography of
      Arabidopsis thaliana expressing red-shifted green fluorescent protein.
AB  - BACKGROUND AND AIMS: Studies have shown that levels of green fluorescent protein
      (GFP) leaf surface fluorescence are directly proportional to GFP soluble protein
      concentration in transgenic plants. However, instruments that measure GFP surface
      fluorescence are expensive. The goal of this investigation was to develop
      techniques with consumer digital cameras to analyse GFP surface fluorescence in
      transgenic plants. METHODOLOGY: Inexpensive filter cubes containing machine
      vision dichroic filters and illuminated with blue light-emitting diodes (LED)
      were designed to attach to digital single-lens reflex (SLR) camera macro lenses.
      The apparatus was tested on purified enhanced GFP, and on wild-type and GFP
      expressing arabidopsis grown autotrophically and heterotrophically. PRINCIPAL
      FINDINGS: Spectrum analysis showed that the apparatus illuminates specimens with
      wavelengths between ~450 and ~500 nm, and detects fluorescence between ~510 and
      ~595 nm. Epifluorescent photographs taken with SLR digital cameras were able to
      detect red-shifted GFP fluorescence in Arabidopsis thaliana leaves and cotyledons
      of pot-grown plants, as well as roots, hypocotyls and cotyledons of etiolated and
      light-grown plants grown heterotrophically. Green fluorescent protein
      fluorescence was detected primarily in the green channel of the raw image files.
      Studies with purified GFP produced linear responses to both protein surface
      density and exposure time (H(0): beta (slope) = 0 mean counts per pixel (ng s mm(
      2))(-1), r(2) > 0.994, n = 31, P < 1.75 * 10(-29)). CONCLUSIONS: Epifluorescent
      digital photographs taken with complementary metal-oxide-semiconductor and charge
      coupled device SLR cameras can be used to analyse red-shifted GFP surface
      fluorescence using visible blue light. This detection device can be constructed
      with inexpensive commercially available materials, thus increasing the
      accessibility of whole-organism GFP expression analysis to research laboratories
      and teaching institutions with small budgets.

PMID- 22479676
TI  - Estimates of nuclear DNA content in red algal lineages.
AB  - BACKGROUND AND AIMS: The red algae are an evolutionarily ancient group of
      predominantly marine organisms with an estimated 6000 species. Consensus higher
      level molecular phylogenies support a basal split between the unicellular
      Cyanidiophytina and morphologically diverse Rhodophytina, the later subphylum
      containing most red algal species. The Rhodophytina is divided into six classes,
      of which five represent early diverging lineages of generally uninucleate
      species, whose evolutionary relationships are poorly resolved. The remaining
      species compose the large (27 currently recognized orders), morphologically
      diverse and typically multinucleate Florideophyceae. Nuclear DNA content
      estimates have been published for <1 % of the described red algae. The present
      investigation summarizes the state of our knowledge and expands our coverage of
      DNA content information from 196 isolates of red algae. METHODOLOGY: The DNA
      localizing fluorochrome DAPI (4',6-diamidino-2-phenylindole) and RBC (chicken
      erythrocytes) standards were used to estimate 2C values with static
      microspectrophotometry. PRINCIPAL RESULTS: Nuclear DNA contents are reported for
      196 isolates of red algae, almost doubling the number of estimates available for
      these organisms. Present results also confirm the reported DNA content range of
      0.1-2.8 pg, with species of Ceramiales, Nemaliales and Palmariales containing
      apparently polyploid genomes with 2C = 2.8, 2.3 and 2.8 pg, respectively.
      CONCLUSIONS: Early diverging red algal lineages are characterized by relatively
      small 2C DNA contents while a wide range of 2C values is found within the derived
      Florideophyceae. An overall correlation between phylogenetic placement and 2C DNA
      content is not apparent; however, genome size data are available for only a small
      portion of red algae. Current data do support polyploidy and aneuploidy as
      pervasive features of red algal genome evolution.

PMID- 22479677
TI  - General practice registrars as teachers: a questionnaire-based evaluation.
AB  - OBJECTIVES: To determine how many General Practice (GP) Registrars in the London
      Deanery taught medical students during their final year of training. For those
      who did teach, to evaluate their experiences and for those who did not, to
      identify perceived barriers to teaching. DESIGN: Cross sectional survey of GP
      Registrars in the London Deanery completing their training in August 2010.
      SETTING: Online survey of GP Registrars sent after completion of training via the
      London Deanery GP Vocational Training Scheme (VTS) programme administrators.
      PARTICIPANTS: GP Registrars in the London Deanery completing their training in
      August 2010. MAIN OUTCOME MEASURE: The proportion of London Deanery GP registrars
      completing training in August 2010 who taught medical students during their
      registrar year. RESULTS: Over half of respondents were involved in some form of
      medical student teaching during their registrar year. Most of those who taught
      felt it enhanced their training, and the majority of those who did not teach
      would have liked to. Commonly cited barriers to teaching were: students not
      attached to the practice; not being given the opportunity to teach; and not
      having time to teach. CONCLUSIONS: This evaluation demonstrated that GP
      registrars are either already involved with undergraduate teaching or want to get
      involved and the majority who teach feel that it enhances their training. A UK
      wide study investigating the experiences and views of both GP registrars and GP
      trainers is warranted and qualitative work using focus groups or semistructured
      interviews would be valuable to develop the questionnaire for wider
      dissemination.

PMID- 22479675
TI  - Non-symbiotic haemoglobins-What's happening beyond nitric oxide scavenging?
AB  - BACKGROUND AND AIMS: Non-symbiotic haemoglobins have been an active research
      topic for over 30 years, during which time a considerable portfolio of knowledge
      has accumulated relative to their chemical and molecular properties, and their
      presence and mode of induction in plants. While progress has been made towards
      understanding their physiological role, there remain a number of unanswered
      questions with respect to their biological function. This review attempts to
      update recent progress in this area and to introduce a hypothesis as to how non
      symbiotic haemoglobins might participate in regulating hormone signal
      transduction. PRINCIPAL RESULTS: Advances have been made towards understanding
      the structural nuances that explain some of the differences in ligand association
      characteristics of class 1 and class 2 non-symbiotic haemoglobins. Non-symbiotic
      haemoglobins have been found to function in seed development and germination,
      flowering, root development and differentiation, abiotic stress responses,
      pathogen invasion and symbiotic bacterial associations. Microarray analyses under
      various stress conditions yield uneven results relative to non-symbiotic
      haemoglobin expression. Increasing evidence of the role of nitric oxide (NO) in
      hormone responses and the known involvement of non-symbiotic haemoglobins in
      scavenging NO provide opportunities for fruitful research, particularly at the
      cellular level. CONCLUSIONS: Circumstantial evidence suggests that non-symbiotic
      haemoglobins may have a critical function in the signal transduction pathways of
      auxin, ethylene, jasmonic acid, salicylic acid, cytokinin and abscisic acid.
      There is a strong need for research on haemoglobin gene expression at the
      cellular level relative to hormone signal transduction.

PMID- 22479678
TI  - Bilateral adrenal haemorrhage presenting as epigastric and back pain.

PMID- 22479679
TI  - Fatal Hyperosmolar Hyperglycaemic Syndrome complicated by severe Rhabdomyolysis.

PMID- 22479680
TI  - Assessment of cardiovascular risk factors prior to NHS Health Checks in an urban
      setting: cross-sectional study.
AB  - OBJECTIVES: To assess the completeness of cardiovascular disease (CVD) risk
      factor recording and levels of risk factors in patients eligible for the NHS
      Health Check. DESIGN: Cross-sectional study. SETTING: Twenty-eight general
      practices located in Hammersmith and Fulham, London, UK. PARTICIPANTS: 42,306
      patients aged 40 to 74 years without existing cardiovascular disease or diabetes.
      MAIN OUTCOME MEASURES: MEASUREMENT AND LEVEL OF CVD RISK FACTORS: blood pressure,
      cholesterol, body mass index (BMI), blood glucose and smoking status. RESULTS:
      There was a high recording of smoking status (86.1%) and blood pressure (82.5%);
      whilst BMI, cholesterol and glucose recording was lower. There was large
      variation in BMI, cholesterol, glucose recording between practices (29.7-91.5%
      for BMI). Women had significantly better risk factor recording than men (AOR =
      1.70 [1.61-1.80] for blood pressure). All risk factors were better recorded in
      the least deprived patient group (AOR = 0.79 [0.73-0.85] for blood pressure) and
      patients with diagnosed hypertension (AOR = 7.24 [6.67-7.86] for cholesterol).
      Risk factor recording varied considerably between practices but was more strongly
      associated with patient than practice level characteristics. Age-adjusted levels
      of cholesterol and BMI were not significantly different between men and women.
      More men had raised blood glucose, blood pressure and BMI than women (29.7% [29.1
      30.4] compared to 19.8% [19.3-20.3] for blood pressure). CONCLUSIONS: Before the
      NHS Health Check, CVD risk factor recording varied considerably by practice and
      patient characteristics. We identified significant elevated levels of raised CVD
      risk factors in the population eligible for a Health Check, which will require
      considerable work to manage.

PMID- 22479681
TI  - Subintimal renal artery angioplasty in a case of renal artery stenosis leading to
      malignant hypertension.

PMID- 22479682
TI  - Pregnancy after complex myomectomy: neither age of patient nor size, number or
      location of fibroids should be a barrier.

PMID- 22479683
TI  - Spontaneous cervical epidural haematoma: role of antiplatelets.

PMID- 22479684
TI  - Targeting novel sites: The N-terminal DNA binding domain of non-LTR
      retrotransposons is an adaptable module that is implicated in changing site
      specificities.
AB  - Restriction-like endonuclease (RLE) bearing non-LTR retrotransposons are site
      specific elements that integrate into the genome through target primed reverse
      transcription (TPRT). RLE-bearing elements have been used as a model system for
      investigating non-LTR retrotransposon integration. R2 elements target a specific
      site in the 28S rDNA gene. We previously demonstrated that the two major sub
      classes of R2 (R2-A and R2-D) target the R2 insertion site in an opposing manner
      with regard to the pairing of known DNA binding domains and bound sequences
      indicating that the A- and D-clades represent independently derived modes of
      targeting that site. Elements have been discovered that group phylogenetically
      with R2 but do not target the canonical R2 site. Here we extend our earlier
      studies to show that a separate R2-A clade element, which targets a site other
      than the canonical R2 site, does so by using the N-terminal zinc fingers and Myb
      motifs. We further extend our targeting studies beyond R2 clade elements by
      investigating the ability of the N-terminal zinc fingers from the nematode NeSL-1
      element to target its integration site. Our data are consistent with the use of
      an N-terminal DNA binding domain as one of the major targeting determinants used
      by RLE-bearing non-LTR retrotransposons to secure a protein subunit near the
      insertion site. This N-terminal DNA binding domain can undergo modifications,
      allowing the element to target novel sites. The binding orientation of the N
      terminal domain relative to the insertion site is quite variable.

PMID- 22479686
TI  - Intrinsic restriction activity by AID/APOBEC family of enzymes against the
      mobility of retroelements.
AB  - A large portion of the mammalian genome is derived from ancient transposable
      elements. Retroelements, transported by an intracellular copy-and-paste process
      involving an RNA intermediate (retrotransposition), constitute a majority of
      these mobile genetic elements. Endogenous retroviruses are LTR-type retroelements
      accounting for around 8% of human or murine genomic DNA. Non-LTR members are
      present in extremely high copy numbers; with LINE-1 contributing to nearly 40% of
      human and murine genomes. These LINE-1 elements modify mammalian genomes not only
      through insertions, but also by indirect replication of nonautonomous
      retrotransposons such as SINEs. As expected, cellular machineries of vertebrate's
      innate immunity have evolved to support a balance between retroelement insertions
      that cause deleterious gene disruptions and those that confer beneficial genetic
      diversity. The ability of APOBEC3 cytidine deaminases targeting DNA to restrict a
      broad number of retroviruses and retro-elements is now well established. More
      recently, the RNA editing family member APOBEC1, a protein involved in lipid
      transport, has also been shown to be involved in keeping mobile elements under
      control. This review discusses current understanding of the mechanism of action
      of the AID/APOBEC family, and their role in controlling the retrotransposition of
      endogenous retroelements.

PMID- 22479685
TI  - Mobile genetic elements in the genus Bacteroides, and their mechanism(s) of
      dissemination.
AB  - Bacteroides spp organisms, the predominant commensal bacteria in the human gut
      have become increasingly resistant to many antibiotics. They are now also
      considered to be reservoirs of antibiotic resistance genes due to their capacity
      to harbor and disseminate these genes via mobile transmissible elements that
      occur in bewildering variety. Gene dissemination occurs within and from
      Bacteroides spp primarily by conjugation, the molecular mechanisms of which are
      still poorly understood in the genus, even though the need to prevent this
      dissemination is urgent. One current avenue of research is thus focused on
      interventions that use non-antibiotic methodologies to prevent conjugation-based
      DNA transfer.

PMID- 22479687
TI  - Association of a centromere specific nucleosome with the yeast plasmid
      partitioning locus: Implications beyond plasmid partitioning.
AB  - The genetically defined point centromeres of budding yeasts and the
      epigenetically specified regional centromeres of all other eukaryotes harbor a
      common epigenetic mark in the form of a non-standard nucleosome. Although, the
      composition of the protein core of the centromere specific nucleosome and the
      nature of the DNA wrap around it are at present controversial, there is no doubt
      that this specialized nucleosome harbors a variant of the standard histone H3
      (cenH3). The association of cenH3, called Cse4 in Saccharomyces cerevisiae, with
      the partitioning locus (STB) of the high copy selfish plasmid 2 micron circle
      that resides in the yeast nucleus and propagates itself stably is intriguing.
      Recent observations are consistent with Cse4 being a nucleosome component at STB.
      A common nucleosome identity for the partitioning loci of the chromosomes and the
      plasmid of yeast support arguments based on evolutionary considerations that the
      origin of the unusual point centromere of budding yeasts may be traced to the STB
      locus of an ancestral plasmid.

PMID- 22479688
TI  - Repetitive sequences, genomic instability and Barrett's esophageal
      adenocarcinoma.
AB  - Barrett's esophageal adenocarcinoma (BAC) is a cancer associated with heartburn.
      If gastroesophageal reflux is not treated, the exposure to acid over the years,
      leads to a premalignant condition known as Barrett's esophagus (BE) which then
      progresses through low grade and high grade dysplasias to Barrett's
      adenocarcinoma. Genomic instability, which seems to arise early at BE stage,
      leads to accrual of mutational changes which underlie the the succession of
      histological and physiological changes associated with this disease. Genomic
      instability is therefore an important target for prevention and treatment of
      cancer and it is important to elucidate the mechanisms associated with this
      problem. We have shown that elevated/deregulated homologous recombination
      mediates genomic instability in cancer. Recently we also demonstrated that the
      mutational rates of individual chromosomes in BAC cells correlate with their ALU
      frequency. The aims of this article are to briefly discuss different types of
      repetitive sequences and highlight their importance in physiology of normal and
      cancer cells, especially BAC.

PMID- 22479689
TI  - Horizontal gene transfer of toxin genes in Clostridium botulinum: Involvement of
      mobile elements and plasmids.
AB  - Intoxication with the potent botulinum neurotoxin (BoNT) gives rise to the
      serious paralytic illness botulism. BoNT is part of a complex that consists of
      the neurotoxin and several associated components, all encoded by the bont gene
      cluster. This gene cluster has likely been subjected to horizontal gene transfer
      between different groups of clostridia, which has given rise to the genetically
      diverse species Clostridium botulinum. C. botulinum is divided into four
      physiological groups (I-IV), where group I and II cause disease in humans and
      group III in animals. Analysis of the genomes of group I, II and III has revealed
      that toxin genes, including the bont cluster, often are plasmid-borne. The
      genomes analyzed from group III contain an unusually high number of plasmids
      carrying different toxin genes. Some of these genes are also found in other
      Clostridium species and some have moved between different plasmids within the
      same physiological group. This indicates that horizontal transfer of toxin genes
      is taking place within and between species of Clostridium. The abundance of
      mobile elements, especially in genomes of group III, is likely connected to
      accelerated genome plasticity and gene transfer events.

PMID- 22479690
TI  - Endosybiotic evolution in action: Real-time observations of chloroplast to
      nucleus gene transfer.
AB  - The origin of new genes has long been considered a fundamental question in
      evolutionary biology. In eukaryotes, a major pathway for the 'birth' of new
      nuclear genes has been transfer of genes from the cytoplasmic organelles
      (mitochondria and plastids) to the nucleus. While the vast majority of gene
      transfer occurred shortly after endosymbiosis, the process continues today and is
      still driving the evolution of nuclear genomes. In tobacco (Nicotiana tabacum) a
      number of studies have indicated that DNA can transfer from the chloroplast to
      the nucleus at relatively high frequency. Less has been known, however, about how
      a newly transferred organelle gene can become activated in this new genetic
      environment. In a recent report we observed, in real-time, the activation of a
      plastid reporter gene newly transferred to the nucleus. A key observation from
      this study was that non-homologous repair is an important generator of novel
      sequence combinations which, in rare instances, can result in the nuclear
      activation of plastid genes. In addition, the activation of relocated genes can
      be aided by the fortuitous presence of plastid sequences able to promote nuclear
      expression.

PMID- 22479691
TI  - Dynamics of gene duplication and transposons in microbial genomes following a
      sudden environmental change.
AB  - The impact of gene duplication on evolution is as ubiquitous as point mutation,
      but this realization is not yet reflected in our quantitative models of
      population genetics. In this Commentary article, we explore the implications of
      such models of gene duplication, specifically expanding on our previous work. We
      lay down a framework for understanding the impact of gene duplications on the
      evolution a biological network and give an analytical argument based on the
      concept of mutational error threshold for the necessity of gene duplications for
      the evolution of complex networks. In other words, by realizing that the impact
      of mutations must act appropriately in order to allow for the maintenance of
      complex networks, we develop a mathematical scaling argument that shows why gene
      duplication provides the types of mutations more favorable to increasing
      complexity. In the process of doing so, we seek to explain the relationship
      between per base pair mutation rates and genome size.

PMID- 22479692
TI  - A septal chromosome segregator protein evolved into a conjugative DNA
      translocator protein.
AB  - Streptomycetes, Gram-positive soil bacteria well known for the production of
      antibiotics feature a unique conjugative DNA transfer system. In contrast to
      classical conjugation which is characterized by the secretion of a pilot protein
      covalently linked to a single-stranded DNA molecule, in Streptomyces a double
      stranded DNA molecule is translocated during conjugative transfer. This transfer
      involves a single plasmid encoded protein, TraB. A detailed biochemical and
      biophysical characterization of TraB, revealed a close relationship to FtsK,
      mediating chromosome segregation during bacterial cell division. TraB
      translocates plasmid DNA by recognizing 8-bp direct repeats located in a specific
      plasmid region clt. Similar sequences accidentally also occur on chromosomes and
      have been shown to be bound by TraB. We suggest that TraB mobilizes chromosomal
      genes by the interaction with these chromosomal clt-like sequences not relying on
      the integration of the conjugative plasmid into the chromosome.

PMID- 22479693
TI  - The evolution of an ancient metazoan biomineralization strategy was supported by
      a horizontal gene transfer.
AB  - The molecular mechanisms that generate morphological novelty are of great
      interest to evolutionary biologists because these are the processes that can
      explain how the diversity of life on earth arose. With advances in sequencing
      technologies, the high-throughput analysis and comparison of entire genomes is
      now possible. Bioinformatic mining of such genome-wide data sets often includes a
      search for horizontal gene transfers (HGTs) as these events can provide exciting
      insight into how morphological, or physiological novelties may have arisen. A
      recent paper by Jackson et al.1 demonstrates that a HGT into the genome of the
      sponge Astrosclera willeyana likely supported the evolution of this animal's
      biomineralization strategy. This HGT, which occurred deep in time, was perhaps a
      key event in the evolution of this animal's body form and would not have been
      detected by certain in silico methods commonly used to screen large data sets.

PMID- 22479694
TI  - Upconversion emission of fluorescent silver nanoclusters and in situ selective
      DNA biosensing.
AB  - Due to their good photostability, high quantum yield and low toxicity,
      fluorescent silver nanoclusters (Ag NCs) have received much attention as novel
      fluorophores for sensing applications. In this work, we investigate the
      upconversion emission of Ag NCs templated by single- and double-stranded DNAs.
      DNA-templated Ag NCs exhibit upconversion emission at wavelengths identical to
      those observed for the corresponding Stokes emission. Consequently, the Ag NCs'
      upconversion behavior can be easily tuned by the used DNA sequences. In addition,
      the Ag NCs are more stable under such an NIR excitation with the upconversion
      mode relative to the Stokes mode. As a proof-of-concept application, DNA
      nucleobase recognition with the in situ formed Ag NCs is realized using the Ag
      NCs' upconversion emission. We expect that the Ag NCs' upconversion emission is
      more advantageous than the previously used rare-earth materials, at least with
      respect to easy modulation of the emission energies by DNA sequences, and could
      find wide application in sensor design.

PMID- 22479695
TI  - Ultra-high performance liquid chromatography-tandem mass spectrometry for the
      analysis of phenicol drugs and florfenicol-amine in foods.
AB  - A method based on ultra-high performance liquid chromatography (UHPLC) is
      proposed for the determination of chloramphenicol (CAP), its related compounds,
      thiamphenicol (TAP) and florfenicol (FF), and the polar metabolite florfenicol
      amine (FFA), in animal-derived foods (chicken and pork meat, fish, prawns and
      honey). For the retention of FFA and its simultaneous analysis with the parent
      compounds a phenyl-hexyl column is proposed. A fast separation is achieved in
      less than 2 minutes using a methanol : acetic acid-ammonium acetate buffer (5 mM,
      pH 5) and gradient elution. Under these conditions, the FFA is retained at more
      than twice the dead volume, as recommended by the legislation. For the coupling
      with mass spectrometry, heated-electrospray (H-ESI) is used as ionisation source
      improving vaporization efficiency. To prevent interferences using selected
      reaction monitoring (SRM) both quantitation and confirmation transitions were
      carefully selected. Two different sample treatments based on solid-phase
      extraction with mixed-mode cartridges for fish and meat products and hydrophilic
      lipophilic-balanced cartridges for honey are proposed, providing limits of
      quantitation (LOQs) below MUg kg(-1) level.

PMID- 22479696
TI  - Synergistic effect of orientation and lateral spacing of protein G on an on-chip
      immunoassay.
AB  - The proper orientation and lateral spacing of antibody molecules are a crucial
      element for an on-chip immunoassay in which the antibody or its antigen-binding
      fragments are immobilized on a solid surface. We covalently immobilized a
      modified protein G (Cys-protein G: protein G with only an N-terminal cysteine) on
      a dendron-coated surface to control its orientation and lateral spacing
      simultaneously. The cysteine-specific immobilization of Cys-protein G through the
      N-terminal cysteine resulted in 2.2-fold higher binding efficiency of Cys-protein
      G to IgG(2a) capture antibody than its random immobilization via lysine residues.
      The lateral spacing of 3.2 nm due to the surface modification with the 9-acid
      dendron molecule contributed to a 1.5-fold increase in the antibody-binding
      ability of Cys-protein G. Topographic images of atomic force microscopy exhibited
      a uniform coverage of Cys-protein G molecules immobilized on the thiol-reactive 9
      acid dendron surface and homogeneous distribution of antibody bound to Cys
      protein G. In the sandwich immunoassay, the control of the orientation of Cys
      protein G led to 10-fold higher detection capability for rIL-2 compared with the
      randomly oriented protein G. The synergistic advantage of the unidirectional
      orientation and homogeneous lateral spacing of Cys-protein Gs on the dendron
      coated surface can be applied to the development of more sensitive and
      reproducible antibody microarrays.

PMID- 22479697
TI  - Molecularly imprinted solid-phase extraction and high-performance liquid
      chromatography with ultraviolet detection for the determination of urinary
      trans,trans-muconic acid: a comparison with ionic exchange extraction.
AB  - A new molecularly imprinted polymer (MIP) has been synthesized for the selective
      extraction of trans,trans-muconic acid (ttMA) from urine samples, followed by
      high-performance liquid chromatography analysis with ultraviolet detection. The
      synthesis was based on non-covalent interactions, and 4-vinylpyridine was used as
      a functional monomer. The analytical calibration curve was prepared using a pool
      of five urine samples of non-smokers spiked with ttMA standards with
      concentrations that ranged from 0.3 to 10 mg L(-1) (r(2) = 0.999). The limit of
      quantification was 0.3 mg L(-1) (lower than the biological exposure limits
      suggested by the ACGIH). The within-day and between-day precision and accuracy
      presented relative standard deviations and relative errors of less than 15%. The
      analytical frequency was 4 h(-1) (considering extraction and
      separation/quantification steps), and the same MIP cartridge was efficiently used
      for approximately 100 cycles. All figures of merit were similar or better than
      those obtained by the procedure based on ionic exchange extraction. The proposed
      method could be an interesting alternative for the routine analysis of ttMA in
      urine for biological monitoring procedures of human exposure to benzene.

PMID- 22479698
TI  - Rapid analysis of whole blood by paper spray mass spectrometry for point-of-care
      therapeutic drug monitoring.
AB  - Paper spray mass spectrometry is applied to oncology drugs in fresh whole blood
      samples supported on filter paper substrates instead of dry blood as done
      previously. Addition of the coagulant alum clotted the blood and allowed for
      immediate sample analysis. The coagulant did not interfere with the function of
      the paper spray nor did it add features to the mass spectra. Quantitative
      analysis of therapeutic drugs in the blood was achieved utilizing internal
      standards which were pre-spotted onto the filter paper. Eight oncology drugs were
      examined, with lower limits of detection ranging between 0.5 and 17 ng mL(-1) and
      linear dynamic ranges greater than two orders of magnitude. Inter-day accuracies
      of quality controls for pazopanib ranged from 102 to 118%, with imprecisions of 9
      to 13%. This one-step method requires 10 MUL of blood, a drop of solvent, and
      takes 45 seconds per trial. These results indicate applicability to point-of-care
      therapeutic drug monitoring in a clinical setting.

PMID- 22479699
TI  - Fluorescence excitation-emission matrix (EEM) spectroscopy and cavity ring-down
      (CRD) absorption spectroscopy of oil-contaminated jet fuel using fiber-optic
      probes.
AB  - Excitation emission matrix (EEM) and cavity ring-down (CRD) spectral signatures
      have been used to detect and quantitatively assess contamination of jet fuels
      with aero-turbine lubricating oil. The EEM spectrometer has been fiber-coupled to
      permit in situ measurements of jet turbine oil contamination of jet fuel.
      Parallel Factor (PARAFAC) analysis as well as Principal Component Analysis and
      Regression (PCA/PCR) were used to quantify oil contamination in a range from the
      limit of detection (10 ppm) to 1000 ppm. Fiber-loop cavity ring-down spectroscopy
      using a pulsed 355 nm laser was used to quantify the oil contamination in the
      range of 400 ppm to 100,000 ppm. Both methods in combination therefore permit the
      detection of oil contamination with a linear dynamic range of about 10,000.

PMID- 22479700
TI  - A solution-based nano-plasmonic sensing technique by using gold nanorods.
AB  - We have successfully demonstrated a novel sensing technique for monitoring the
      variation of solution concentrations and measuring the effective dielectric
      constant in a medium by means of an ultra-small and label-free nanosensor, the
      mechanism of which is based on the localized surface plasmon resonance (LSPR) of
      gold nanorods. The nanorods are fabricated in a narrow size distribution, which
      is characterized by transmission electron microscopy and optical absorption
      spectroscopy. In addition, we employ a simple analytical calculation to examine
      the LSPR band of the absorption spectrum, which provides excellent consistency
      with aspect ratio. The plasmonic sensing is performed by detecting the diffusion
      process and saturation concentration of hexadecyltrimethylammonium bromide in
      water, and tracing the effective dielectric constants of the medium
      simultaneously. This promising sensing and analytical technique can be easily
      used for investigating the nano-scale variations of mixing or reaction process in
      a micro/nanofluidic channel or the biological interaction in the cytoplasm of the
      cell.

PMID- 22479701
TI  - Organellar signalling. Preface.

PMID- 22479702
TI  - International trends in transfusion therapy.

PMID- 22479703
TI  - Editor's commentary: commentary on the March 2012 issue.

PMID- 22479704
TI  - In silico prediction of the granzyme B degradome.
AB  - BACKGROUND: Granzyme B is a serine protease which cleaves at unique tetrapeptide
      sequences. It is involved in several signaling cross-talks with caspases and
      functions as a pivotal mediator in a broad range of cellular processes such as
      apoptosis and inflammation. The granzyme B degradome constitutes proteins from a
      myriad of functional classes with many more expected to be discovered. However,
      the experimental discovery and validation of bona fide granzyme B substrates
      require time consuming and laborious efforts. As such, computational methods for
      the prediction of substrates would be immensely helpful. RESULTS: We have
      compiled a dataset of 580 experimentally verified granzyme B cleavage sites and
      found distinctive patterns of residue conservation and position-specific residue
      propensities which could be useful for in silico prediction using machine
      learning algorithms. We trained a series of support vector machines (SVM)
      classifiers employing Bayes Feature Extraction to predict cleavage sites using
      sequence windows of diverse lengths and compositions. The SVM classifiers
      achieved accuracy and AROC scores between 71.00% to 86.50% and 0.78 to 0.94
      respectively on independent test sets. We have applied our prediction method on
      the Chikungunya viral proteome and identified several regulatory domains of viral
      proteins to be potential sites of granzyme B cleavage, suggesting direct
      antiviral activity of granzyme B during host-viral innate immune responses.
      CONCLUSIONS: We have compiled a comprehensive dataset of granzyme B cleavage
      sites and developed an accurate SVM-based prediction method utilizing Bayes
      Feature Extraction to identify novel substrates of granzyme B in silico. The
      prediction server is available online, together with reference datasets and
      supplementary materials.

PMID- 22479705
TI  - Prokaryotic RNAi.

PMID- 22479708
TI  - Commentary on Incidence and cost of serious fall-related injuries in nursing
      homes.

PMID- 22479706
TI  - Network-based functional enrichment.
AB  - BACKGROUND: Many methods have been developed to infer and reason about molecular
      interaction networks. These approaches often yield networks with hundreds or
      thousands of nodes and up to an order of magnitude more edges. It is often
      desirable to summarize the biological information in such networks. A very common
      approach is to use gene function enrichment analysis for this task. A major
      drawback of this method is that it ignores information about the edges in the
      network being analyzed, i.e., it treats the network simply as a set of genes. In
      this paper, we introduce a novel method for functional enrichment that explicitly
      takes network interactions into account. RESULTS: Our approach naturally
      generalizes Fisher's exact test, a gene set-based technique. Given a function of
      interest, we compute the subgraph of the network induced by genes annotated to
      this function. We use the sequence of sizes of the connected components of this
      sub-network to estimate its connectivity. We estimate the statistical
      significance of the connectivity empirically by a permutation test. We present
      three applications of our method: i) determine which functions are enriched in a
      given network, ii) given a network and an interesting subnetwork of genes within
      that network, determine which functions are enriched in the sub-network, and iii)
      given two networks, determine the functions for which the connectivity improves
      when we merge the second network into the first. Through these applications, we
      show that our approach is a natural alternative to network clustering algorithms.
      CONCLUSIONS: We presented a novel approach to functional enrichment that takes
      into account the pairwise relationships among genes annotated by a particular
      function. Each of the three applications discovers highly relevant functions. We
      used our methods to study biological data from three different organisms. Our
      results demonstrate the wide applicability of our methods. Our algorithms are
      implemented in C++ and are freely available under the GNU General Public License
      at our supplementary website. Additionally, all our input data andresults are
      available at http://bioinformatics.cs.vt.edu/~murali/supplements/2011-incob-nbe/.

PMID- 22479709
TI  - Particle therapy.

PMID- 22479710
TI  - Current world literature.

PMID- 22479723
TI  - [Reconstruction of the aortic base using a stentless artificial valve in complex
      aortic root infection].

PMID- 22479724
TI  - [Imaging diagnosis: Q & A. Abnormal findings in the upper right lung field].

PMID- 22479725
TI  - Guest editorial about nurses' titles garners appreciation.

PMID- 22479727
TI  - Abstracts of the 6th Internal Medicine Congress with International Participation,
      September 23-26, 2010, Opatija, Croatia.

PMID- 22479726
TI  - Guest editorial about nurses' titles garners appreciation.

PMID- 22479728
TI  - [Proceedings of the VI Congress on the Radiobiological Research (Radiobiology,
      Radioecology, Radiation Safety), October 25-28, 2010, Moscow, Russia].

PMID- 22479729
TI  - [Streptococcus bovis endocarditis that presented a difficulty in differentiating
      from urinary tract infection and collagen disease].

PMID- 22479730
TI  - [Two cases of familial liver abscess].

PMID- 22479731
TI  - Festschrift in honor of Martin J. Ball.

PMID- 22479732
TI  - Current good manufacturing practice in manufacturing, processing, packing, or
      holding of drugs; revision of certain labeling controls. Final rule.
AB  - The Food and Drug Administration (FDA) is amending the packaging and labeling
      control provisions of the current good manufacturing practice (CGMP) regulations
      for human and veterinary drug products by limiting the application of special
      control procedures for the use of cut labeling to immediate container labels,
      individual unit cartons, or multiunit cartons containing immediate containers
      that are not packaged in individual unit cartons. FDA is also permitting the use
      of any automated technique, including differentiation by labeling size and shape,
      that physically prevents incorrect labeling from being processed by labeling and
      packaging equipment when cut labeling is used. This action is intended to protect
      consumers from labeling errors more likely to cause adverse health consequences,
      while eliminating the regulatory burden of applying the rule to labeling unlikely
      to reach or adversely affect consumers. This action is also intended to permit
      manufacturers to use a broader range of error prevention and labeling control
      techniques than permitted by current CGMPs.

PMID- 22479733
TI  - Student health insurance coverage. Final rule.
AB  - This final rule establishes requirements for student health insurance coverage
      under the Public Health Service (PHS) Act and the Patient Protection and
      Affordable Care Act (Affordable Care Act). The final rule defines "student health
      insurance coverage" as a type of individual health insurance coverage, and
      specifies that certain PHS Act requirements are inapplicable to this type of
      individual health insurance coverage. This final rule also amends the medical
      loss ratio and annual limits requirements for student health insurance coverage
      under the PHS Act.

PMID- 22479734
TI  - Medical devices; neurological devices; classification of the Near Infrared Brain
      Hematoma Detector. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the Near Infrared (NIR)
      Brain Hematoma Detector into class II (special controls). The Agency is
      classifying the device into class II (special controls) in order to provide a
      reasonable assurance of safety and effectiveness of the device.

PMID- 22479735
TI  - Medicaid program; eligibility changes under the Affordable Care Act of 2010.
      Final rule, Interim final rule.
AB  - This final rule implements several provisions of the Patient Protection and
      Affordable Care Act of 2010 and the Health Care and Education Reconciliation Act
      of 2010 (collectively referred to as the Affordable Care Act). The Affordable
      Care Act expands access to health insurance coverage through improvements to the
      Medicaid and Children's Health Insurance (CHIP) programs, the establishment of
      Affordable Insurance Exchanges ("Exchanges"), and the assurance of coordination
      between Medicaid, CHIP, and Exchanges. This final rule codifies policy and
      procedural changes to the Medicaid and CHIP programs related to eligibility,
      enrollment, renewals, public availability of program information and coordination
      across insurance affordability programs.

PMID- 22479736
TI  - Patient Protection and Affordable Care Act; standards related to reinsurance,
      risk corridors, and risk adjustment. Final rule.
AB  - This final rule implements standards for States related to reinsurance and risk
      adjustment, and for health insurance issuers related to reinsurance, risk
      corridors, and risk adjustment consistent with title I of the Patient Protection
      and Affordable Care Act as amended by the Health Care and Education
      Reconciliation Act of 2010, referred to collectively as the Affordable Care Act.
      These programs will mitigate the impact of potential adverse selection and
      stabilize premiums in the individual and small group markets as insurance reforms
      and the Affordable Insurance Exchanges ("Exchanges") are implemented, starting in
      2014. The transitional State-based reinsurance program serves to reduce
      uncertainty by sharing risk in the individual market through making payments for
      high claims costs for enrollees. The temporary Federally administered risk
      corridors program serves to protect against uncertainty in rate setting by
      qualified health plans sharing risk in losses and gains with the Federal
      government. The permanent State-based risk adjustment program provides payments
      to health insurance issuers that disproportionately attract high-risk populations
      (such as individuals with chronic conditions).

PMID- 22479737
TI  - Patient Protection and Affordable Care Act; establishment of exchanges and
      qualified health plans; exchange standards for employers. Final rule, Interim
      final rule.
AB  - This final rule will implement the new Affordable Insurance Exchanges
      ("Exchanges"), consistent with title I of the Patient Protection and Affordable
      Care Act of 2010 as amended by the Health Care and Education Reconciliation Act
      of 2010, referred to collectively as the Affordable Care Act. The Exchanges will
      provide competitive marketplaces for individuals and small employers to directly
      compare available private health insurance options on the basis of price,
      quality, and other factors. The Exchanges, which will become operational by
      January 1, 2014, will help enhance competition in the health insurance market,
      improve choice of affordable health insurance, and give small businesses the same
      purchasing clout as large businesses.

PMID- 22479738
TI  - Removal of regulations on black lung benefits. Final rule.
AB  - This final rule removes regulations on the Black Lung program from the Social
      Security Administration's (SSA) chapter of the Code of Federal Regulations (CFR).
      The Black Lung Consolidation of Administrative Responsibility Act transferred the
      responsibility for administering Part B of the Black Lung benefits program from
      SSA to the Department of Labor (DOL), and we are removing the regulations in
      recognition of the fact that we are no longer responsible for administering any
      aspect of the Part B Black Lung program. DOL concurs with this final rule
      removing the regulations.

PMID- 22479739
TI  - Dementia and depression.

PMID- 22479740
TI  - Oral versus intravenous steroids in acute exacerbation of asthma--randomized
      controlled study.
AB  - BACKGROUND: Use of corticosteroids in asthma is a must however the route of
      administration of steroid in acute exacerbation is a matter of debate.
      Intravenous steroids used very frequently in clinical practice may not offer any
      advantage over oral steroids. AIM: To compare to the efficacy of oral vs
      intravenous steroids in adults admitted with acute exacerbation of bronchial
      asthma. METHODS: Adults admitted to hospital with acute exacerbation of asthma
      were randomized to receive oral prednisolone 100 mg once daily or hydrocortisone
      100 mg i.v. 6 hourly for 72 hrs following admission. All patients concurrently
      received inhaled corticosteroids and bronchodilators. Improvements in peak
      expiratory flow rate (PEF) from baseline were compared for 72 hrs. RESULTS: A
      total of 65 patients were randomized, 34 received oral prednisolone and 31
      received intravenous hydrocortisone. Both groups were matched at baseline for age
      (40 +/- 13.11 vs 44 +/- 16.23, p 0.27) and percentage prediction both pre (20.11%
      +/- 6.17 vs 20.58% +/- 4.78, p 0.73) and post bronchodilator (24.35% +/- 5.43 vs
      25.38% +/- 5.01, p 0.43). After 72 hrs both groups had improvement in PEF which
      was statistically insignificant (53.23% +/- 9.54 vs 55.87% +/- 10.34, p 0.28).
      CONCLUSION: Corticosteroids administered orally and IV had similar efficacy in
      the treatment of adults hospitalized with acute exacerbation of bronchial asthma.

PMID- 22479741
TI  - Mild cool air--a risk factor for asthma exacerbations: results of a retrospective
      study.
AB  - BACKGROUND AND OBJECTIVES: Worldwide incidence of bronchial asthma is on rise.
      Infections either viral or bacterial and various environmental factors are
      considered as major risk factors for exacerbations in various studies. Despite of
      awareness and preventive strategies to risk factors, exacerbations largely remain
      uncontrolled, therefore the study was planned to review the existing risk factors
      and to find out some other risk factor/factors which could help us in
      understanding the other causes of exacerbations. METHODS: The study was done in
      Ajmer, the central part of Rajasthan state, India, at Mittal Hospital & Research
      Centre and J. L. N. Medical college hospital by collecting data for the period of
      four years (January 2006 - December 2009). Monthly record of 300 regular cases of
      bronchial asthma was taken. This record included symptoms, history of exposure to
      various risk factors, and PEFR. Environmental data was also collected. On the
      basis of record monthly attack rate was calculated. RESULTS/OBSERVATIONS: Maximum
      attack rate (> 90%) was found in October, November (early winter) and February
      and March (spring) during all the four years studied except in October 2009. A
      common precipitant present during these months was mild cool air (environmental
      temperature of 23-27 degrees c). Attack rate was very less above and below of
      this temperature. No clear association was present with any other known
      precipitants. CONCLUSION: It is concluded that inhalation of mild coolair (23-27
      degrees c) may be an important risk factor besides other risk factors for asthma
      exacerbation.

PMID- 22479742
TI  - Attitudinal determinants of fasting in type 2 diabetes mellitus patients during
      Ramadan.
AB  - OBJECTIVE: Fasting during Ramadan has been dissuaded by the physicians for
      patients of Diabetes, yet fasting being a religious issue can not be made a
      contraindication for those who are determined. The aim of present study was to
      find out whether counseling prior to Ramadan can result in successful fasting
      with lesser adverse events. We have also studied clinical, social and demographic
      factors causing attitudinal difference in patients and its effect on fasting and
      diabetes control. RESEARCH DESIGN AND METHODS: We recruited 96 (males 54, Females
      42) Muslim patients of Type 2 Diabetes, 2-3 weeks prior to Ramadan. Patients were
      educated about lifestyle, diet and medications. Awareness regarding diabetes
      management during fasting was assessed by a scored questionnaire prior to and
      after Ramadan. Last year Ramadan's experiences were recorded for comparison, on a
      recall basis. RESULT: There was increase in post Ramadan awareness score. Average
      increase in awareness score was more in rural patients (1.23 +/- 3.76; n = 52)
      than in urban (1.09 +/- 2.01; n = 44). Average number of fasts had positive
      correlation with duration of Diabetes. There was significant increase (p < 0.05)
      in the number of fasts kept this year. Maximum increase was in the age group 40
      60 year (25.74%). Fifteen days fast was completed by all patients on diet
      control, 81.3% patients on OHA and 35.7% on insulin. Hypertensive patients had
      more hypoglycemic episodes. Lesser number of tobacco addicts could fast for > 15
      days. No patient needed hospitalization or emergency care. CONCLUSION: Fasting in
      Type2 Diabetes patients during Ramadan can be facilitated with safer outcomes and
      lesser adverse events. Individual attitude is important as increases in awareness
      and education are not linked to specific improved end-points.

PMID- 22479743
TI  - Depression in patients of myocardial infarction--a cross-sectional study in
      northern India.
AB  - OBJECTIVES: To assess the prevalence of major depressive disorder and
      subsyndromal depression in patients with first episode of myocardial infarction
      (MI) and to compare the socio-demographic, clinical and coronary risk factors in
      patients with and without depression. METHODS: Patients of acute MI (n = 101)
      attending OPD at 4 to 6 weeks after the index event were the subjects. Diagnoses
      of Major Depressive Disorder were established according to Diagnostic and
      Statistical Manual for Mental Disorders fourth edition Test Revision (DSN-IV-TR)
      criteria. Schedule for Affective Disorder and Schizophrenia changed version
      modified for Bipolar disorder (SADS-CB) was applied to detect cases with
      depressive symptoms not amounting to major depressive disorder (sub-syndromal).
      It was a single point cross sectional study. RESULTS: No depressive symptoms
      (Group-A) were found in 56 patients (55.4%). Major Depressive Disorder (Group-B)
      was found in 24 patients (23.8%) and subsyndromal symptoms (Group-C) in 21
      patients (20.8%). Sociodemographic and clinical variables were similar amongst
      three groups except, more patients in Group-C were from nuclear family (p = 0.01)
      and were educated (p = 0.03). More patients in Group-B had hypertension (p =
      0.001), diabetes (p = 0.03) or were overweight (p = 0.02) as compared to Group-A.
      Similarly higher number of Group-C patients had hypertension (p = 0.04), diabetes
      (p = 0.01) and were current smokers (p = 0.01) as compared to Group-A.
      CONCLUSION: Unrecognized and untreated major depressive disorder and sub
      syndromal symptoms were frequent in patients of MI. Established coronary factors
      were more commonly present in these groups as compared to no depressive symptom
      group. This emphasizes the need for routine screening for depression in post MI
      phase in our population.

PMID- 22479744
TI  - Association of depression with complications of type 2 diabetes--the Chennai
      Urban Rural Epidemiology Study (CURES- 102).
AB  - OBJECTIVE: The aim of the study was to assess the relationship between depression
      and diabetic complications among urban south Indian type 2 diabetic subjects
      [T2DM]. METHODS: T2DM subjects [n = 847] were recruited from the Chennai Urban
      Rural Epidemiology Study [CURES], a population based study in Chennai (formerly
      Madras) in South India. A previously validated depression questionnaire [PHQ-12
      item] was administered. Four field stereo retinal colour photography was done and
      diabetic retinopathy [DR] was classified according to the Early Treatment
      Diabetic Retinopathy Study grading system. Neuropathy was diagnosed if the
      vibratory perception threshold of the right great toe, measured by
      biothesiometry, was > or = 20. Nephropathy was diagnosed if urinary albumin
      excretion was > or = 300 microg/mg creatinine. Peripheral vascular disease [PVD]
      was diagnosed if an ankle-brachial index was < 0.9. Coronary artery disease [CAD]
      was diagnosed based on a past history of documented myocardial infarction and/or
      electrocardiographic evidence of Q wave and/or ST segment changes. RESULTS: Of
      the 847 T2DM studied, 198 (23.4%) were found have depression. The prevalence of
      depression was significantly higher among diabetic subjects with DR (35.0% vs
      21.1%, p < 0.001), neuropathy (28.4% vs 15.9%, p = 0.023), nephropathy (35.6% vs
      24.5%, p = 0.04) and PVD (48.0% vs 27.4%, p < 0.001) as compared to subjects
      without these complications. DR, neuropathy, nephropathy, and PVD were associated
      with depression even after adjusting for age, gender, duration of diabetes and
      glycated haemoglobin. DR (Odds ratio [OR] = 2.19, Confidence interval [CI]:1.45
      3.51, p < 0.001) was associated with depression even after adjusting for
      neuropathy and nephropathy. There was also a significant association between
      depression and neuropathy, after adjusting for retinopathy and nephropathy (OR =
      2.07, CI: 1.41-3.04, p < 0.001). There was a significant association of
      depression with nephropathy but this was lost (OR = 1.71, CI: 0.87-3.35, p =
      0.119) after adjustment for retinopathy. PVD (OR = 3.52, CI: 1.94-6.40, p <
      0.001) remained significantly associated with depression even after adjusting for
      CAD. However, there was no significant association of depression with CAD (OR =
      0.73, CI: 0.42 -1.27, p = 0.264). CONCLUSION: Among Asian Indians, the prevalence
      of depression is higher in T2DM subjects with retinopathy, neuropathy,
      nephropathy and PVD compared to those without the respective complications.

PMID- 22479745
TI  - Depression in dementia patients: issues and challenges for a physician.
AB  - Depression and dementia share a complex and interesting relationship, with a
      possibility of biological linkages between the two disorders. Research has shown
      consistently increased prevalence of depression in patients suffering from
      dementia. As many as one fourth to half of dementia patients are likely to
      experience clinical depression during the course of illness. However, the onset
      of depressive symptoms is often misinterpreted as worsening of cognitive decline
      and hence, it remains under-diagnosed. The lack of a coherent account from
      patient, frequent overlap of symptoms, inadequate sensitization of physicians may
      enhance the diagnostic difficulty. Undetected depression adds to patient
      disability and caregiver burden. Early recognition and proper intervention will
      improve the patient outcomes including quality of life. Selective serotonin
      reuptake inhibitors, especially Sertraline and Citalopram, with a very gradual
      dose titration are likely to benefit. Certain behavioral interventions e.g
      involvement of patient in physical activity and pleasant activities has been
      found to be useful. All dementia cases should be routinely screened for
      depression and managed accordingly.

PMID- 22479746
TI  - Diffuse mucocutaneous leishmaniasis.

PMID- 22479747
TI  - Lipemia retinalis.

PMID- 22479748
TI  - Levetiracetam.
AB  - Levetiracetam (LEV) is a novel antiepileptic drug (AED) which was discovered in
      early 1980s and soon, in 1999 FDA approved LEV for the management of partial
      onset seizure. In India, LEV tablet was approved in April 2005. It acts by
      binding to the synaptic vesicle protein SV2A, which is present on synaptic
      vesicles and some neuroendocrine cells. Pharmacokinetics of LEV such as, less
      protein binding and lack of hepatic metabolism makes LEV less susceptible to drug
      interactions with other anticonvulsants. Evidence also suggests that LEV is much
      better than other AEDs in the way of broad therapeutic window, convenient dosing
      and less adverse effect. Besides the pharmacological effects,
      pharmacoeconomically also, LEV is a beneficial drug. All these valuable
      pharmacological and pharmacoeconomic aspect makes LEV an important option in
      management of various types of epilepsy.

PMID- 22479749
TI  - Massive hemoptysis during pregnancy.
AB  - We report a case of pulmonary carcinoid presenting as massive hemoptysis in a
      pregnant patient. In our patient, diagnosis of carcinoid tumor was suspected
      after ruling out other probable and possible causes of hemoptysis. It was
      confirmed provisionally on flexible fiber optic bronchoscopy and later confirmed
      on histopathology. Our patient had two consecutive emergency surgeries, emergency
      cesarean section on one day followed by emergency pneumonectomy on next day. The
      lives of both, the mother and baby could be saved. At three month follow up, the
      mother did not have any symptoms.

PMID- 22479750
TI  - Young male with systemic lupus erythematosus presenting with sensorineural
      deafness with immune suppression induced miliary tuberculosis.
AB  - A 32 year male presented with deafness and other classical symptoms suggestive of
      SLE. Subsequent serological investigations confirmed the diagnosis. Renal biopsy
      showed the presence of SLE induced Grade V nephropathy. Patient was started on
      NIH protocol for lupus nephritis on which he was doing well. After two years, he
      presented with symptoms of miliary tuberculosis and was started on ATD.
      Subsequently, he developed ATD induced hepatotoxicity and had to be switched over
      to Inj. Streptomycin containing regimen. We thought to share this clinical
      experience, as we found it a challenge to manage tuberculosis in such a setting,
      where a fine balance had to be maintained between immunosuppression for SLE and
      therapy of TB, and an ototoxic drug had to be used in a patient with deafness
      induced by SLE.

PMID- 22479751
TI  - Mycotic aneurysm of the popliteal artery due to infective endocarditis.
AB  - Mycotic aneurysm (MA) is an infrequent complication of infective endocarditis
      (IE), reported in 3 to 15% of the patients with IE. The commonest site for such
      aneurysm is intracranial vessels (65%) followed by abdominal and then the
      peripheral vessels. We describe a case of 32 year old man with recently diagnosed
      rheumatic heart disease and mitral regurgitation. He had infective endocarditis
      (IE) and developed a large mycotic popliteal artery aneurysm (MPAA) and a small
      profunda femoris arterial aneurysm (PFAA) while he was on antibiotic therapy. The
      patient was successfully treated with prolonged antibiotic therapy and
      embolisation of the MPAA while PFAA was managed conservatively.

PMID- 22479752
TI  - Rare variety of T-cell lymphoma.
AB  - We report a case of 18 year old male who presented with hepatosplenomegaly,
      anemia and thrombocytopenia. His complete hemogram, peripheral smear, bone marrow
      studies were inconclusive. On immunophenotyping he was diagnosed as
      "Hepatosplenic gamma delta (gammadelta) T cell lymphoma" which is a very rare
      variety of T cell lymphoma. Less than 100 cases have been described in the
      literature since the entity was first described in 1990.

PMID- 22479753
TI  - Familial episodic ataxia type II.
AB  - The familial episodic ataxia type II is a rare, dominantly inherited disease
      characterized by episodes of ataxia of early onset, often with completely normal
      cerebellar function between attacks. We report a family with affected members who
      had features of episodic ataxia type II and cerebellar atrophy on MRI imaging.
      All the affected members were successfully treated with acetazolamide, a carbonic
      anhydrase inhibitor. They are asymptomatic at 2 year follow-up.

PMID- 22479754
TI  - Superior mesenteric artery syndrome secondary to tuberculosis induced cachexia.
AB  - Superior mesenteric artery (SMA) syndrome is a rare cause of obstruction of 3rd
      part of duodenum between abdominal aorta and the overlying superior mesenteric
      artery caused by decrease in the angle between the two vessels as a result of
      rapid loss of retroperitoneal fat. It is seen in conditions causing severe weight
      loss and catabolic states. We report a case of pulmonary tuberculosis leading to
      superior mesenteric artery syndrome.

PMID- 22479755
TI  - 42 years old male with single atrium.
AB  - Single atrium (SA) is a rare congenital anomaly characterized by absence or
      virtual absence of atrial septum, vestigial remnant of which occasionally remain.
      We report here such a case of SA who presents his symptoms in different way of
      its natural course of presentation.

PMID- 22479756
TI  - Medical philately. Egaz Moniz.

PMID- 22479757
TI  - Mildly elevated transaminases: excellent diagnostic clue for anicteric
      leptospirosis.

PMID- 22479758
TI  - Scleroderma cardiac disease.

PMID- 22479759
TI  - Swine flu encephalitis--first adult case report from India.

PMID- 22479760
TI  - There are infections other than TB please!

PMID- 22479761
TI  - "Badges can instil pride and raise care standards".

PMID- 22479762
TI  - Sick nurses "must get AFc pay rise".

PMID- 22479764
TI  - "So who was invited to the PM's summit? The pop group Steps"?

PMID- 22479763
TI  - "Care home safety must not play second fiddle to the acute sector".

PMID- 22479765
TI  - "Clinicians must not bottle out of advising on formula feeds".

PMID- 22479766
TI  - Therapeutic use of cannabis.
AB  - Therapeutic cannabis use raises a number of dilemmas for nurses. This article
      examines the legal, political and ethical challenges raised by the use of
      cannabis by people with life-limiting or terminal illnesses in their own homes.
      (Throughout this paper, the term cannabis refers to illegal cannabis unless
      specified.) A literature review of databases from 1996 was conducted and internet
      material was also examined. Evidence on the therapeutic use of cannabis suggests
      it may produce improvements in quality of life, which has led to increased use
      among people with life-limiting illnesses. The cannabis used is usually obtained
      illegally, which can have consequences for both those who use it and nurses who
      provide treatment in the community.

PMID- 22479767
TI  - Would decriminalising drugs improve care?
AB  - The decriminalisation of illegal drugs is controversial. This article examines
      the debate in the UK, and argues that a change in the laws would help to remove
      stigma and consequently change health professionals' attitudes towards drug users
      and improve services.

PMID- 22479768
TI  - Do ward housekeepers free up time for care?
AB  - Introducing a ward housekeeping service may give nursing staff more time to focus
      on essential care. This small-scale evaluation found the role freed up healthcare
      assistant time and improved staff morale.

PMID- 22479769
TI  - Using vignettes to teach stroke care.
AB  - Although nurses are best placed to meet the needs of patients with stroke and
      their carers, evidence suggests they are inadequately prepared for this role.
      This article discusses the use of vignettes as a teaching and learning tool to
      develop pre-registration student nurses' knowledge of stroke management. An
      evaluation found they could be a useful learning tool for use throughout the
      nurse education programme.

PMID- 22479771
TI  - Practical problem solver.

PMID- 22479772
TI  - Encourage staff to live by your values.

PMID- 22479770
TI  - Very brief advice on smoking.

PMID- 22479773
TI  - Opinion piece: Kellogg's should stick to Corn Flakes.

PMID- 22479774
TI  - The successful dental practice. Part Two: Anti-establishment dentistry and the
      emergence of the CE rock star.

PMID- 22479775
TI  - Oral Pathology Quiz #74. Case number 1. Adult gingival cyst.

PMID- 22479776
TI  - Oral Pathology Quiz #74. Case number 2. Lateral periodontal cyst.

PMID- 22479777
TI  - Oral Pathology Quiz #74. Case number 3. Frictional hyperkeratosis.

PMID- 22479778
TI  - Oral Pathology Quiz #74. Case number 4. Lichenoid mucositis.

PMID- 22479779
TI  - Case report: Patient with acute dental pain has cardiac valve replacement--INR
      3.8. What to do? What not to do?
AB  - Cardiovascular medicine treatments now include an increasing number of cardiac
      valve replacements; approximately 60,000 patients may undergo heart valve
      replacement per year. Dentists will be seeing an increasing number of patients
      who have undergone this surgical intervention. This paper will overview the types
      of valve replacements and suggested patient management in the dental setting. A
      case report of one such patient and the treatment provided is presented.

PMID- 22479780
TI  - Case study: what would you do?

PMID- 22479781
TI  - Extractions, immediate implant placement and ridge preservation utilizing
      alloplastic bone graft material. Report of a case.
AB  - A case report of extractions of periodontally involved teeth with immediate
      implant placement and ridge preservation using alloplastic material is discussed.
      The bone graft substitute was for bone maintenance in the extraction sockets and
      around the dental implants. The case is followed for over one year through the
      restorative phase.

PMID- 22479782
TI  - A review of vitamin D as it relates to periodontal disease.
AB  - Vitamin D has classically been known as a "bone hormone." But recently, vitamin D
      has been found to play a role in respect to systemic diseases such as
      cardiovascular disease, cancer, and periodontal disease. It has been reported
      that approximately 1 billion people worldwide are either vitamin D deficient or
      insufficient. This paper will address the various roles that vitamin D plays in
      respect to systemic diseases, the effects of vitamin D deficiency, and how it is
      diagnosed and treated.

PMID- 22479783
TI  - Saliva as a tool in the detection of hepatitis B surface antigen in patients.
AB  - Viral hepatitis is one of the world's most common viral illnesses. Hepatitis B
      virus infection is a global health problem, and its importance in dentistry is
      well recognized. The role of saliva in the transmission of hepatitis B makes
      dentists and dental personnel particularly vulnerable to hepatitis B infection.
      The objective of this study was to predict the efficacy of saliva as a tool for
      the detection of hepatitis B surface antigen (HBsAg), which is the hallmark of
      the infection. The study group comprised 70 patients, 35 of whom were known to be
      hepatitis B infection seropositive (test group) and the remaining 35 who did not
      have hepatitis B (control group). All of the subjects were tested with enzyme
      linked immunosorbant assay. Of the 35 seropositive subjects, HBsAg was detected
      in the saliva samples of 26 subjects. The sensitivity and specificity of saliva
      as a diagnostic tool for detecting HBsAg antigen in this study was 74.29% and
      100%, respectively. Because of its noninvasive nature, saliva can be effectively
      used for large-scale Hepatitis B virus detection.

PMID- 22479784
TI  - Localized idiopathic apical root resorption: a report of five cases with emphasis
      on differential diagnosis.
AB  - Seeking to describe the clinical and radiologic features of localized idiopathic
      apical root resorption (LIAR), the authors conducted a dental literature review
      of idiopathic external root resorption and performed a retrospective study of
      LIAR among the identified cases retrieved from a private general practice. Cases
      involved five patients--one female and four males--ranging in age from 15 to 48
      years. The authors concluded that LIAR appears to be a distinct but uncommon
      clinicopathologic condition that is self-limiting, and therefore warrants no
      definitive treatment. However, the condition, which can present asymptomatically
      on routine radiographs or is sometimes associated with clinical symptoms,
      warrants differentiation from periapical replacement resorption as a result of
      orthodontics or trauma.

PMID- 22479785
TI  - Restoration of a fractured central incisor.
AB  - The treatment of a traumatically damaged single central incisor poses significant
      challenges relative to function and esthetics to the restoring clinician.
      Providing a good long-term prognosis is paramount when determining whether to
      maintain or extract a structurally compromised tooth. Successful restoration
      demands timely and thorough risk assessment along with excellent communication
      with both the patient and the laboratory fabricating the restoration.

PMID- 22479786
TI  - Effect of an herbal mouth rinse in preventing periodontal inflammation in an
      experimental gingivitis model: a pilot study.
AB  - BACKGROUND: Gingivitis is a chronic inflammatory condition, resulting from
      gingival bacteria and bacterial byproducts. Antiplaque oral rinses reduce
      inflammation by removing or inhibiting plaque formation. The purpose of this
      pilot study was to examine the anti-inflammatory effects of HM-302, a mouth rinse
      based on natural products, on gingival inflammation. METHODS: A prospective,
      double-blinded, randomized parallel-group controlled trial involving 62 patients
      was conducted to assess efficacy and safety. During a 2-week period with no
      dental hygiene, subjects were randomized to receive either the study rinse (HM
      302); a cetylpyridinium chloride (CPC) rinse; an essential oils (EO) rinse; or a
      water-only preparation. The gingival index (GI), plaque index (PI), and number of
      bleeding sites were measured at baseline and at the end of the study period.
      RESULTS: Progression of gingival inflammation resulting from lack of dental
      hygiene was lowest in patients treated with the HM-302 rinse, and was
      significantly less marked than in patients treated with the water-only
      preparation. When compared to the CPC and EO treatments, HM-302 was the only
      mouth rinse that was significantlybetter than the control, with respect to both
      the change in absolute GI scores (p = .006) and to the percent increase in GI
      scores (p = .012). No serious adverse effects were noted in any of the study
      groups. CONCLUSION: HM-302 is a safe and effective treatment for preventing the
      development of gingival inflammation in an experimental gingivitis model. Further
      research is needed to evaluate its long-term effects.

PMID- 22479787
TI  - The durability of the resin/dentin complex.

PMID- 22479788
TI  - BISCO sets sights on creating the best adhesives.

PMID- 22479789
TI  - Simplicity is the key to Danville's Prelude adhesive.

PMID- 22479790
TI  - Kuraray provides "tried and true" adhesive options.

PMID- 22479791
TI  - Managing craniofacial pain the multi-disciplinary way.

PMID- 22479792
TI  - I am TNA.

PMID- 22479793
TI  - High-tech and high-touch: it doesn't just happen.

PMID- 22479794
TI  - United we stand, divided we will fall.

PMID- 22479795
TI  - Stand up! Claiming our profession.

PMID- 22479796
TI  - Nurses in northeast tennessee working toward IOM recommendations for many years.

PMID- 22479797
TI  - Turmoil continues as NMC faces another review.

PMID- 22479798
TI  - Vitamin D deficiency guidelines to be reviewed.

PMID- 22479799
TI  - Is it too late to stop the Bill?

PMID- 22479800
TI  - Exploring attitudes and behaviour towards teenage pregnancy.
AB  - This article illustrates a methodological approach, which actively engaged 14 to
      19 year olds in the research process. This two phase study explored the attitudes
      and behaviours of young people towards teenage pregnancy in Northamptonshire, UK.
      The first phase involved training young mothers to lead six focus groups with
      three specifically targeted 'at-risk' groups; other teenage mothers, young
      offenders and looked after children (from 14 to 19 years of age). An open
      question began each focus group but the young women or peer researchers were
      aware of the topics they wished to explore and provided prompts as necessary.
      Seven topics are presented under the headings of: alcohol and drugs; planned
      pregnancy; professionals' treatment; need for love; support by family, friends
      and partners; labelling and the reality for teenage mothers; and future
      aspirations. The reasons for pregnancy or consequences of pregnancy are discussed
      under the implications and recommendations.

PMID- 22479801
TI  - Learning practice: a new model of health visitor intervention to drive outcomes.
AB  - Although there is a body of literature related to how hospital nurses develop
      skill, judgement or expertise there is little empirical work that focuses on
      understanding and developing health visiting expertise. The aims of this paper
      are: to identify a typology of health visitor skills, knowledge and cognition in
      use and the nature of health visitor expertise; to present an expert model of
      practice as a practice learning tool; to locate this model in context of my 2007
      empirical research. This explored the problems of families and children in need
      and how they were supported by health visitors. This new practice model is timely
      in view of the need to train more health visitors, educators and practice
      facilitators as set out in the Health Visitor Implementation Plan.

PMID- 22479802
TI  - The Strengthening Families Programme 10-14 (UK): engagement and academic success
      at school.
AB  - The changes that young people experience during early adolescence increase the
      risk that they may not reach their full potential. Poor parenting skills and an
      adverse family environment exacerbate existing behavioural problems and often
      result in academic failure. There is an expanding body of research supporting the
      important role of parents, family and community in determining young people's
      academic success in school. Parent and family-mediated interventions that target
      parenting skills have been shown across multiple intervention studies to be the
      most effective for reducing risk behaviour and preventing the development of
      later problem behaviour in adolescence. This article reports on the
      implementation of one such family intervention -the SFP10-14 (UK)- in a school in
      the north of England. It suggests a number of ways that practitioners working in
      the community can engage with families through family-mediated interventions to
      promote academic success in early adolescence.

PMID- 22479804
TI  - Engaging with and encouraging people to stop smoking.

PMID- 22479803
TI  - Meeting the health needs of disabled parents.

PMID- 22479805
TI  - The adoption of telecare in the community.

PMID- 22479806
TI  - NHS risk register: what is the Department of Health afraid of?

PMID- 22479807
TI  - Getting educated and staying educated.

PMID- 22479808
TI  - Enjoying healthy eating: fiber.

PMID- 22479809
TI  - Apple-Raisin Bran muffins.

PMID- 22479810
TI  - How much do you know about ketones?

PMID- 22479811
TI  - Your annual comprehensive foot exam.

PMID- 22479812
TI  - Supermarket smarts. Chocolate.

PMID- 22479814
TI  - What your doctor is reading.

PMID- 22479813
TI  - Continuous glucose monitoring: troubleshooting common problems.

PMID- 22479815
TI  - An algorithm for network motif discovery in biological networks.
AB  - Network motif discovery is a key problem in analysis of biological networks. In
      this paper, we present an efficient algorithm for detecting consensus motifs.
      First, we extend subgraph searching algorithm Enumerate Subgraphs (ESU) to
      efficiently search non-treelike subgraphs of which the probability of occurrence
      in random networks is small. Then, we classify isomorphic subgraphs into
      different groups. Finally, we use hierarchical clustering method to cluster
      subgraphs, and derive a consensus motif from the clusters. Our algorithm is
      applied to the Protein-Protein Interaction (PPI) networks and the transcriptional
      regulatory networks of E. coli and S. cerevisiae. The experiment results show
      that the algorithm can efficiently discover motifs, which are consistent with
      current biology knowledge. And, it can also detect several consensus motifs with
      a given size, which may help biologists go further into cellular process.

PMID- 22479816
TI  - Several remarks on the metric space of genetic codes.
AB  - A genetic code, the mapping from trinucleotide codons to amino acids, can be
      viewed as a partition on the set of 64 codons. A small set of non-standard
      genetic codes is known, and these codes can be mathematically compared by their
      partitions of the codon set. To measure distances between set partitions, this
      study defines a parameterised family of metric functions that includes Shannon
      entropy as a special case. Distances were computed for 17 curated genetic codes
      using four members of the metric function family. With these metric functions,
      nuclear genetic codes had relatively small inter-code distances, while
      mitochondrial codes exhibited greater variance. Hierarchical clustering using
      Ward's algorithm produced a tight grouping of nuclear codes and several distinct
      clades of mitochondrial codes. This family of functions may be employed in other
      biological applications involving set partitions, such as analysis of microarray
      data, gene set enrichment and protein-protein interaction mapping.

PMID- 22479817
TI  - GemAffinity: a scoring function for predicting binding affinity and virtual
      screening.
AB  - Prediction of protein-ligand binding affinities plays an essential role for
      molecular recognition and virtual screening. We have developed a scoring
      function, namely GemAffinity, to predict binding affinities by using a stepwise
      regression method and 88 descriptors from 891 complex structures. GemAffinity
      consists of five descriptors, including van der Waals contacts; metal-ligand
      interactions; water effects; ligand deformation penalty; and conserved hydrogen
      bonded residues. Experimental results indicate that GemAffinity is the best among
      13 methods on a test set and can enrich screening accuracies on four sets. We
      believe that GemAffinity is useful for virtual screening and drug discovery.

PMID- 22479818
TI  - Clustering PPI data based on improved functional-flow model through quantum
      behaved PSO.
AB  - Clustering Protein-Protein Interaction (PPI) data is a difficult problem due to
      its small world and scale-free characteristics. Existing clustering methods could
      not perform well. This paper proposes an improved functional-flow based approach
      through Quantum-behaved Particle Swarm Optimisation (QPSO) algorithm, which can
      find the optimum threshold automatically when calculating the lowest similarity
      between modules. We also take bridging nodes into account to improve the
      clustering result. The experiments on Munich Information Center for Protein
      Sequences (MIPS) PPI data sets show that the algorithm has better performance
      than functional flow method in terms of accuracy and number of matched clusters.

PMID- 22479819
TI  - Inference system using softcomputing and mixed data applied in metabolic pathway
      datamining.
AB  - This paper describes the development of an inference system used for the
      identification of genes that encode enzymes of metabolic pathways. Input sequence
      alignment values are used to classify the best candidate genes for inclusion in a
      metabolic pathway map. The system workflow allows the user to provide feedback,
      which is stored in conjunction with analysed sequences for periodic retraining.
      The construction of the system involved the study of several different
      classifiers with various topologies, data sets and parameter normalisation data
      models. Experimental results show an excellent prediction capability with the
      classifiers trained with mixed data providing the best results.

PMID- 22479820
TI  - Improved differential evolution for microarray analysis.
AB  - Clustering is an important tool for analysing the microarray data to identify
      groups of co-expressed genes. The problem of fuzzy clustering in microarray data
      motivated us to develop an improved clustering algorithm. In this paper, an
      improved differential evolution based fuzzy clustering technique is proposed. The
      performance of the proposed improved differential evolution based fuzzy
      clustering technique has been compared with other state-of-the-art clustering
      algorithms for publicly available benchmark microarray data sets. Statistical and
      biological significance tests have been carried out to establish the statistical
      superiority of the proposed clustering approach and biological relevance of
      clusters of co-expressed genes, respectively.

PMID- 22479821
TI  - iMOWSE, a scoring scheme bridging in silico and in vitro digestion in PMF.
AB  - We demonstrated an unexplored issue in Peptide Mass Fingerprinting, 'cleavage
      site clusters', and formulated iMOWSE to distinguish true positives from false
      positives. We showed how the cleavage site clusters skew peptide database
      composition. Concerning the information content of an in silico digestion of a
      protein, both the number of matches of long peptides and the number of such
      peptides an entry can generate are taken into account. The resultant iMOWSE
      allows tolerance of deviation of query mass values from theoretical mass values
      and fewer matches are needed to identify true positives.

PMID- 22479823
TI  - Community services slow to adopt new technology.

PMID- 22479822
TI  - Testing patients' patience.

PMID- 22479824
TI  - Matron receives award for saving lives in Libya conflict.

PMID- 22479825
TI  - Initiative to reduce reliance on agency staff.

PMID- 22479826
TI  - Barcode checks.

PMID- 22479827
TI  - Survey explores nurses' of e-health tools.
AB  - E-health is concerned with promoting the health and wellbeing of individuals,
      families and communities, and improving professional practice through the use of
      information management and information and communication technology. In autumn
      2010 the RCN, supported by an information technology consultancy, carried out a
      survey of members' views on e-health to assess their involvement in, and
      readiness for, e-health developments and their knowledge of its benefits. A total
      of 1,313 nurses, midwives, healthcare support workers and pre-registration
      students from across the UK responded. This article describes ways in which nurse
      managers can influence the successful implementation of the survey
      recommendations.

PMID- 22479828
TI  - Transformational leadership can improve workforce competencies.
AB  - Staffing problems can arise because of poor delegation skills or a failure by
      leaders to respond appropriately to economic factors and patient demographics.
      Training dilemmas, meanwhile, can arise because of managers' confusion about what
      constitutes 'training' and what constitutes 'education', and where responsibility
      of provision lies, with the consequence that they neglect these activities. This
      article uses Kouzes and Posner's (2009) transformational leadership model to show
      how managers can respond. Leaders who challenge budgets, consider new ways of
      working and engage effectively with the workforce can improve productivity and
      care, while those who invest in appropriate learning will have a highly trained
      workforce. The author explains how integration of leadership roles and management
      functions can lead to innovative problem solving.

PMID- 22479829
TI  - Contrasting perceptions about the delivery of care in the community.
AB  - UK government policy emphasises the role of leadership in meeting the NHS
      healthcare quality agenda. As care is delivered increasingly in the community, it
      is important to evaluate the quality of nursing care provided to patients and
      families in community settings. However, few quality indicators have been
      designed for use in this sector. A study was undertaken to examine the effects of
      nursing leadership in the community on quality of care, and the results suggest
      that there is tension between nurse 'leaders' and 'followers' about the value of
      leadership. While nurse leaders see the leadership role as critical to improving
      quality through workforce planning and organisation, front line staff perceive
      individual nurse's skills as more pertinent to the quality of community nursing
      care.

PMID- 22479830
TI  - How to address the physical needs of clients in a mental health setting.
AB  - People with mental health illness, particularly those affected in the long-term,
      experience higher rates of morbidity and mortality than the general population.
      It is, therefore, crucial to meet their physical health needs as part of
      delivering a high quality service. This article reports on how nurses in a medium
      secure mental health unit used the 'plan, do, study, act' approach (Deming 1986)
      as a practice improvement tool to introduce a system of monitoring the physical
      health of service users.

PMID- 22479831
TI  - Exploring the evidence.

PMID- 22479832
TI  - Nurses to face public scrutiny.

PMID- 22479833
TI  - "Display outcome data on wards to boost care and motivate staff".

PMID- 22479834
TI  - "It's easier to moonwalk than be a student nurse these days".

PMID- 22479835
TI  - "Why don't we ask patients what they thought of their care?".

PMID- 22479836
TI  - Barriers to managing and improving quality.
AB  - Although the term "quality" is frequently used in healthcare, there is confusion
      over what it means and how to improve it. The Chartered Quality Institute
      commissioned a survey to investigate staff views on quality and its
      implementation. This article reports on the results and makes recommendations.

PMID- 22479837
TI  - Treating staggered paracetamol overdose.

PMID- 22479838
TI  - "Teaching injection technique will improve quality of life".

PMID- 22479839
TI  - Injection technique in insulin therapy.
AB  - Ensuring that people with diabetes use correct injection techniques for insulin
      therapy is a vital part of nurses' role. This article outlines key aspects of
      good injection technique and emphasises the importance of ongoing patient
      education and regular reviews of knowledge and technique.

PMID- 22479840
TI  - Changing practice for safe insulin administration.
AB  - Insulin is a life-saving medication but, if wrongly administered, it can cause
      death or severe harm. Errors in insulin administration are common, including the
      inappropriate use of intravenous syringes. We surveyed all clinical areas in our
      trust to identify types of syringes and needles available and how these were
      stored and distinguished from IV syringes. Based on these results, we developed
      recommendations to promote safety and good practice and are standardising insulin
      syringes throughout the trust.

PMID- 22479841
TI  - Improving diabetes care.

PMID- 22479842
TI  - South Asian cultural concepts in diabetes.
AB  - BACKGROUND: Type 2 diabetes is a significant health problem in the South Asian
      community. AIM: To extract messages from primary research reports to improve
      nurses' cultural understanding so they are better able to promote self-management
      among people of South Asian origin with type 2 diabetes. METHOD: A review was
      conducted of studies describing people from this group, cultural concepts of
      their diabetes management and the impact of culturally sensitive care. RESULTS:
      Eight studies involved adults of South Asian origin, with three focused solely on
      the Bangladeshi community. They all explored cultural perceptions of diabetes and
      self-management. CONCLUSION: Cultural beliefs play an important role in attitudes
      towards diabetes among people of South Asian origin. Understanding their beliefs
      improves the care provided to this community.

PMID- 22479843
TI  - 60 seconds with Yvonne Sawbridge.

PMID- 22479844
TI  - Critical care in Cambodia.

PMID- 22479845
TI  - Stop people feeling like the odd one out.

PMID- 22479846
TI  - It's got to be right.

PMID- 22479847
TI  - Level of female genital mutilation in the UK is unacceptable says RCM.

PMID- 22479848
TI  - Emergencies during home births.
AB  - This article reflects on how community midwifery skills days have assisted
      community midwives to develop confidence in managing unexpected emergencies at
      home births, and how team work, communication and working in partnership have
      supported women in their choices for birth.

PMID- 22479849
TI  - At home in early labour: what fathers do and how they feel--part 3.
AB  - This is the third in a series of three articles which present data from a 2010
      survey completed by 263 fathers on their experience of being at home with their
      partner in early labour. Fathers' state of mind during early labour is explored.
      Anxiety levels are found to be high, particularly in regard to the wellbeing of
      their partners and babies. Attending antenatal classes does not appear to
      diminish anxiety and often, nor does speaking to a midwife in early labour. These
      results require cautious interpretation but also suggest that men need better
      preparation for their role in supporting mothers during labour.

PMID- 22479850
TI  - Breech birth: an unusual normal.
AB  - Over the last decade, there has been a loss in confidence and eroded skills due
      to the near universal policy of advising caesarean section in the wake of the
      Term Breech trial (Hannah et al 2000). Breech birth has been increasingly viewed
      as a complication, and management of the breech presenting baby at term has
      shifted firmly into the realm of obstetric practice in most parts of the UK.
      Small pockets of exception remain, among NHS and independent midwives who have
      maintained their skills with breech birth and are sought out by women denied the
      choice of a vaginal birth elsewhere. With continued focus on consumer choice,
      women led care and increasing normality, we urgently need to address the issue of
      how the NHS can safely provide the option of normal breech birth before these
      skills are permanently lost. This article suggests ways midwives may play a role
      within the NHS in ensuring women have a choice to birth their breech babies
      normally, in the safest possible way.

PMID- 22479851
TI  - Midwives, labour induction and the Wooden Spoon award part I.
AB  - Labour induction rates have rocketed, largely due to consumer demands and
      provider convenience. This increase has been a significant factor in rapidly
      increasing caesarean birth rates and adverse perinatal outcomes. It is important
      that midwives understand the risks associated with labour induction. The article
      overviews those factors contributing to increasing induction rates and the
      associated risks. Midwives are challenged to consider the evidence for an
      intervention contributing to a cascade of birth interventions.

PMID- 22479852
TI  - Midwifery in Scotland.
AB  - Responsibility for health services in Scotland was devolved to the Scottish
      Parliament in 1999. This inevitably has led to differences within the UK as to
      how maternity services are shaped and delivered and aims to ensure that
      initiatives are tailor made for the Scottish population and its health needs.
      Changes within the Maternity services have been led and supported by policies
      such as A framework for maternity services (Scottish Executive 2001) and Keeping
      Childbirth Natural and Dynamic (KCND) (NHS Quality Improvement Scotland (NHS QIS)
      2009) which promotes multi professional working and has developed and implemented
      care pathways.

PMID- 22479853
TI  - Facilitating a midwifery book club.
AB  - A midwifery student book club was set up at University Campus Suffolk (UCS) with
      the aim of engaging students in alternative forms of literature relevant to their
      studies and to enhance their university experience. The book club was well
      attended by first and second year midwifery students, but less so by third years.
      There was evidence of informal student engagement with the lecturer through
      follow up emails about the meetings. Most of the books reviewed were enjoyed, but
      the responsibility of suggesting a book for their peers to review was deemed too
      much by some students.

PMID- 22479854
TI  - Use of technology in childbirth: 6. Phototherapy.

PMID- 22479855
TI  - Help for parents at night.

PMID- 22479856
TI  - The best laid plans of women and midwives.

PMID- 22479857
TI  - Re: Who determines the standard of care?

PMID- 22479858
TI  - Dental patients and blood pressure monitoring: is your office following
      recommendations?

PMID- 22479859
TI  - Is marketing through Groupon legal?

PMID- 22479860
TI  - The latest on employment law posters.

PMID- 22479861
TI  - Internet coupons and professional ethics.

PMID- 22479862
TI  - The top 10 leadership challenges for dentists.

PMID- 22479863
TI  - What is hypertension?

PMID- 22479864
TI  - Treatment of hypertension: a physician's perspective.

PMID- 22479865
TI  - Is the recession really over in Michigan?

PMID- 22479866
TI  - Dental contracts '201'.

PMID- 22479867
TI  - Do we really provide patient-centered care?

PMID- 22479868
TI  - For better or for worse--values shape nursing practice.

PMID- 22479869
TI  - The alcohol-dependent patient in hospital: challenges for nursing.
AB  - Individuals who are alcohol dependent pose significant challenges for nurses when
      they are admitted to hospital for treatment. Clinical problems presented by these
      individuals are examined and the critical aspects of their care are highlighted.

PMID- 22479870
TI  - Nursing practice breakdowns: good and bad nursing.
AB  - Nurses' responsibility to provide good patient care is explored. Nursing practice
      breakdowns are examined, differentiating unintentional errors from intentional
      acts. Good and bad nursing care is portrayed through an emerging classification
      of intentional practice breakdowns.

PMID- 22479871
TI  - Hourly rounding: a replication study.
AB  - Preventing falls in hospitalized patients, increasing patient satisfaction, and
      decreasing call light usage are constant challenges nurses face every day. This
      quasi-experimental study replicates Meade, Bursell, and Ketelsen's (2006) study
      on a rounding protocol, demonstrating improvements in the above variables.

PMID- 22479872
TI  - Staffing patterns of scheduled unit staff nurses vs. float pool nurses: a pilot
      study.
AB  - In this study, the differences in patient assignments between float pool nurses
      versus scheduled unit staff nurses were examined. Although there was a tendency
      for float pool nurses to receive more difficult patient assignments, this was not
      statistically significant (at alpha=0.05).

PMID- 22479873
TI  - Relationship of respiratory care bundle with incentive spirometry to reduced
      pulmonary complications in a medical general practice unit.
AB  - To address an increase in patient transfers to the intensive care unit because of
      respiratory distress, a respiratory care bundle utilizing incentive spirometry
      was developed for a medical general practice unit. This resulted in decreased
      respiratory complications over 12 months.

PMID- 22479874
TI  - Hyperglycemic state.

PMID- 22479875
TI  - U-charts.

PMID- 22479876
TI  - Oral gallstone dissolution therapies.
AB  - Surgery is still the recommended and proven effective management for
      cholelithiasis. However, when surgery poses more risk than benefits or if
      surgical management is refused, oral dissolution therapy may be a helpful
      alternative, providing patients relief from biliary colic and preventing further
      formation and accumulation of gallstones while therapy is ongoing.

PMID- 22479877
TI  - Nurses' personal liability vs. employer's vicarious liability.

PMID- 22479878
TI  - Creating a multimedia interprofessional geriatric resource web site.

PMID- 22479879
TI  - Physician identification of opioid diversion: a difficult diagnosis.

PMID- 22479880
TI  - Palliative care in the management of lung cancer: analgesic utilization and
      barriers to optimal pain management.
AB  - OBJECTIVE: Little data exist on assessing pain medication utilization among lung
      cancer patients or on the reasons they fail to receive optimal analgesic
      treatment. This study evaluates those reasons and investigates perceived causes
      of pain among individuals with lung cancer. DESIGN: An institutional review board
      approved Internet-based questionnaire was posted on http://www.oncolink.org that
      included 22 queries evaluating analgesic utilization, pain control, and attitudes
      regarding analgesics. PATIENTS AND PARTICIPANTS: Between November 2005 and July
      2008, 90 respondents with lung malignancies participated. Respondents were
      Caucasian (89 percent), male (54 percent), and had non-small-cell lung cancer (79
      percent), small-cell lung cancer (12 percent), or mesothelioma (9 percent).
      RESULTS: Respondents underwent surgery (48 percent), chemotherapy (58 percent),
      and radiotherapy (44 percent). Most respondents (92 percent) reported
      experiencing pain, with 52 percent attributing pain directly to cancer, 38
      percent to cancer treatment, and 67 percent unsure of the primary cause. Among
      respondents experiencing pain, 33 percent did not use analgesics. Analgesic
      utilization was less in men (p = 0.050) but did not differ by minority status (p
      = 0.127), education level (p = 0.37), or lung cancer histology (p = 0.134).
      Analgesic use was higher in subjects receiving radiotherapy (p = 0.002) and
      chemotherapy (p = 0.013) but not surgery (p = 0.16). Reasons for not taking
      analgesics included fear of addiction/dependence (76 percent), healthcare
      providers not recommending medications (71 percent), and inability to pay for
      analgesics (56 percent). Participants pursued physical therapy (76 percent) and
      other complementary modalities (24 percent) for pain control. CONCLUSIONS: Many
      individuals with lung cancer perceive pain from both their disease and their
      cancer treatment. However, some study respondents did not use analgesics due to
      concerns of addiction, cost, or their healthcare providers not recommending
      analgesics. Medicalprofessionals providing medical management for lung cancer
      patients should make pain management a priority and regularly discuss pain
      symptoms and pain management with patients.

PMID- 22479881
TI  - Report of an HIV clinic-based pain management program and utilization of health
      status and health service by HIV patients.
AB  - CONTEXT: Current reports on human immunodeficiency virus (HIV) pain are limited
      to epidemiological data on neuropathic pain in HIV and most studies were
      conducted before the availability of highly active antiretroviral therapy.
      Complex pain was reported to be highly prevalent and associated with advanced
      disease. OBJECTIVES: The authors conducted a retrospective review of the medical
      records of 81 patients from the Center for Positive Living (CPL) at Montefiore
      Medical Center who were newly referred to a pain management program in 2006 to
      identify the potential benefits of integrating a pain management team into the
      care of persons living with HIV and etiologies of pain. METHODS: A standardized
      chart abstraction tool was used to capture clinical data. Data related to health
      service utilization and viral outcomes were obtained from the clinical
      information systems. RESULTS: The most common pain diagnoses were multiple
      syndromes, degenerative disc disease or spinal stenosis, and neuropathy. There
      was a decrease in emergency room utilization in the 12 months following an
      initial pain management appointment (p < 0.0001) and an increase in use of
      primary care (p = 0.0017). The use of adjuvant medications increased after intake
      into the pain clinic (p < 0.0001). Having an opioid dose in excess of 200 mg/d
      oral morphine equivalents and maintenance of each palliative care and infectious
      disease clinic appointment were inversely associated with viral loads in excess
      of 75 copies: odds ratio (OR) = 0.21 (95% confidence interval/CI], 0.11-0.44), OR
      = 0.77 (95% CI, 0.68-0.86), and 0.94 (95% CI, 0.93-0.99), respectively.
      CONCLUSIONS: The decrease in emergency room visits and increase in use of
      adjuvant analgesics and compliance with primary care and nonmedication approaches
      for the management of pain in the 12 months subsequent to initial palliative/pain
      clinic appointments highlight potential improved quality of care associated with
      the integration of a pain management team into the primary care of persons living
      with HIV disease.

PMID- 22479882
TI  - Buprenorphine therapy for opioid addiction in rural Washington: the experience of
      the early adopters.
AB  - BACKGROUND: The introduction of buprenorphine as office-based treatment for
      opioid dependence was designed to expand treatment capacity, but virtually there
      are no data about use of this medication in rural areas. METHODS: The survey of
      the first cohort of physicians in rural Washington State who obtained
      buprenorphine waivers (2002-2010) to determine the volume of treated patients,
      physician appraisal of the efficacy of this treatment, and perceived barriers to
      treatment was conducted. Twenty-four (73 percent) of the 33 rural buprenorphine
      certified physicians practicing in the state were interviewed in 2010. RESULTS:
      Twenty physicians (83 percent) were actively prescribing buprenorphine/naloxone
      for treatment of addiction. Those currently prescribing averaged 23 active
      patients and had treated 125 patients since certification. All respondents
      reported that buprenorphine was efficacious in the treatment of addiction and 95
      percent recommended that other rural colleagues adopt buprenorphine treatment.
      The following four major barriers were cited: 1) lack of adequate financial
      support from Medicaid, the largest source of third-party coverage for these
      patients; 2) unavailability of local mental health and behavioral addiction
      treatment services; 3) difficulty in finding consultants to assist in managing
      complex patients; and 4) shortages of other rural physicians providing this
      service. CONCLUSIONS: Buprenorphine is viewed as a highly effective treatment of
      opioid addiction by early adopters in rural Washington State, but relatively few
      rural physicians currently provide this service. Inadequate insurance coverage, a
      shortage of effective links with consultants and colleagues, and the lack of
      mental health services are persistent barriers to the use of this modality in
      rural Washington State.

PMID- 22479883
TI  - PCA-derived factors that may be predictive of postoperative pain in pediatric
      patients: a possible role for the PCA ratio.
AB  - OBJECTIVE: No method exists to reliably predict which patients will develop
      severe postoperative pain. The authors hypothesized that data derived from
      patient-controlled analgesia (PCA) pumps (specifically the ratio of patient
      demands to pump deliveries) may predict which patients would develop severe pain
      after scoliosis repair. SETTING: Quaternary, university-affiliated, pediatric
      hospital. PATIENTS AND PARTICIPANTS: Forty American Society of Anesthesiologists
      I-Il pediatric patients who had undergone elective scoliosis repair and had
      consented to recruitment to a randomized clinical trial investigating the effects
      of early morphine administration on remifentanil-induced hyperalgesia.
      INTERVENTIONS: To test the hypothesis of the current study, the authors
      calculated the PCA ratio of demand to delivery at every 4 hours throughout the
      first 24 hours after surgery for all the patients recruited to the original
      study. MAIN OUTCOME MEASURES: The authors compared calculated PCA ratios, numeric
      rating scale pain scores, and cumulative morphine consumption for those patients
      who developed severe postoperative pain and met the criteria for opioid rotation
      versus those patients who did not. RESULTS: Seven patients required opioid
      rotation from PCA morphine to PCA hydromorphone. Eight hours after surgery, the
      median PCA ratio for those seven patients (2.5[range, 1.8-4.3]) was significantly
      greater than that for all other recruited patients (1.3 [range, 0-2.7]; p <
      0.001). CONCLUSIONS: Patients who developed severe postoperative pain and met the
      criteria for opioid rotation demonstrated significantly increased PCA ratios of
      demand to delivery as early as 8 hours after surgery.

PMID- 22479884
TI  - Urinalysis-based comparative evaluation of pattern of use of dextropropoxyphene
      and buprenorphine among opioid-dependent subjects.
AB  - OBJECTIVE: In view of increasing safety concerns, there is a need to assess
      benefits of use of dextropropoxyphene as opioid substitution treatment, if any.
      This study aims at urinalysis-based comparative evaluation of pattern of use of
      dextropropoxyphene and buprenorphine among opioid-dependent subjects. SETTING:
      Laboratory of a tertiary care drug-dependence treatment center. PARTICIPANTS:
      Patients on buprenorphine and dextropropoxyphene therapy and their urinalysis
      records. INTERVENTIONS: Nonexperimental chart review method. MAIN OUTCOME
      MEASURE(S): "Use," "abuse, "and 'prescribed but not used rates" for buprenorphine
      and dextropropoxyphene were compared, using chi2-test with level of significance
      at p < 0.05. RESULTS: Rate of "use" and "abuse" was significantly high for
      dextropropoxyphene. Rate of 'prescribed but not used" was significantly high for
      buprenorphine (p < 0.05). CONCLUSIONS: Despite apparent benefits of
      dextropropoxyphene use in terms of better rates of "use" and 'prescribed but not
      used" as compared to buprenorphine, one needs to review the situation in light of
      recent reports of adverse effects with dextropropoxyphene and limited resources
      available.

PMID- 22479885
TI  - Should morphine dosing be weight based for analgesia in the emergency department?
AB  - OBJECTIVE: To determine if patient weight is predictive of the degree of
      analgesic response to morphine in opioid naive patients in the emergency
      department (ED). DESIGN: Prospective observational study. SETTING: Academic,
      tertiary ED, designated as a level 1 trauma center. PATIENTS: Fifty opioid naive
      adult patients who were administered a single fixed intravenous dose of 4 mg
      morphine on initial presentation to the ED. INTERVENTIONS: Pain was assessed at
      baseline and then repeated at 15- and 30-minute postdose using an 11-point (0-10)
      verbal numerical rating scale (NRS). MAIN OUTCOME MEASURES: The primary outcome
      was maximum analgesic response, which is defined as the difference between
      initial pain score and lowest pain score achieved postdose at 15 or 30 minutes.
      Linear regression was used to analyze the relationship between maximum pain
      reduction and patient weight. RESULTS: Mean patient weight was 85.4 kg (standard
      deviation = +/- 24.2; range 47.6-170). Median initial pain score was 8 (range 6
      10) and median lowest pain score achieved postdose was 4 (range 0-10). In the
      linear regression analysis, patient weight did not predict the degree of pain
      reduction on the NRS (coefficient = 0.002 [95% confidence interval (CI) = -0.029
      0.032], R2 < 0.001, p = 0.91). The only variable predictive of the degree of pain
      reduction was initial pain score (coefficient = 0.537/95% CI = 0.013-1.0611, R2 =
      0.081,p = 0.045). CONCLUSIONS: Patient weight was not significantly associated
      with the degree of analgesic response to morphine in opioid naive adults.
      Morphine dosing based on patient weight alone is not necessary in adults in the
      ED.

PMID- 22479886
TI  - The opioid manager: a point-of-care tool to facilitate the use of the Canadian
      Opioid Guideline.
AB  - The Opioid Manager is designed to be used as a point-of-care tool for providers
      prescribing opioids for chronic noncancer pain. It condenses the key elements
      from the Canadian Opioid Guideline and can be used as a chart insert. The Opioid
      Manager has been validated and is available for download from the Guideline's Web
      site http://nationalpaincentre.mcmaster.ca/opioidmanager/. The Opioid Manager is
      divided into the following four parts: A) before you write the first script, B)
      initiation trial, C) maintenance and monitoring, and D) when is it time to
      decrease the dose or stop the opioid completely? The Opioid Manager has been
      downloaded by 1,432 users: 47 percent family physicians, 18 percent pharmacists,
      13 percent other physicians, and 22 percent miscellaneous. To show how to use the
      Opioid Manager, the authors created a 10-minute video that is available on the
      Internet. The Opioid Manager is being translated to French, Spanish, Portuguese,
      and Farsi.

PMID- 22479888
TI  - Opioid withdrawal-induced hypomania: a case series.
AB  - The aim of this study was to report hypomanic symptoms after opioid withdrawal.
      In this case series, nine opioid-dependent patients with hypomanic profile on
      opioid withdrawal were selected from outpatients in a private psychiatric clinic.
      Opium dependency was diagnosed according to Diagnostic and Statistical Manual of
      Mental Disorders (Fourth Edition). Substance history, clinical features,
      temperament, and family history were retrospectively probed. Patients displayed
      pure or mixed hypomanic symptoms on opioid withdrawal. In nearly all subjects,
      the symptoms continued until individuals started taking the opioid again.
      Features of hyperthymic temperament and family history of bipolarity were traced
      in most of the individuals.

PMID- 22479887
TI  - Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin
      overdose.
AB  - A case of heroin overdose reversed through the intravenous (IV) administration of
      a crushed sublingual tablet of buprenorphine/naloxone (Suboxone) by a lay
      responder is described. Although the sublingual administration of
      buprenorphine/naloxone to reverse an overdose has been reported elsewhere, this
      is the first report of IV administration. Healthcare professionals should be
      aware that injection drug users may respond to an opioid overdose by injecting
      buprenorphine/naloxone and should consequently counsel all opioid-using patients
      on the proper response to an overdose. Physicians should also consider
      prescribing naloxone to at-risk patients. The work of community-based naloxone
      distribution programs should be expanded.

PMID- 22479889
TI  - [Frequency and characteristics for forceps delivery].
AB  - AIM: To establish the incidence of vaginal operative deliveries by extraction of
      the fetus with forceps and the degree of prematurity of newborns in which it is
      applied, to specify the type of forceps which is imposed. MATERIAL AND METHODS:
      The study included 672 births, completed by extraction of the fetus with forceps
      in the period 1994-2008 year in University hospital "Maichin dom" Sofia. The
      total number of births was 47,130, of which 32,924 have become per vias
      naturalis. Age of birth was from 13 to 42 years. The study was done prospectively
      and retrospectively. RESULTS: The incidence of forceps extraction of the total
      number of births for the period is 1.43%, as seen following the trend - in the
      first years of the period 1994 - 1995 is more than 2% of total births, in the
      period 1996 to 2003 years and then fluctuated between 1 and 2%, and after 2004
      has decreased below 1%. There could be noticed slight and gradual reduction in
      the incidence of operative vaginal delivery by forceps. The general incidence of
      forceps extraction compared to vaginal births was 2.04% for the entire period, at
      the beginning is 3.5% and then fell between 2.5 and 2% for the period 1995 to
      2003 years, then in 2004 was between 1 and 2%. In 94.8% of cases forceps was
      applied to term fetuses and 5.2% of cases in preterm fetuses (respectively 3.78%
      in premature fetuses 1-st degree, 1.10 percent premature fetuses II-nd degree and
      0.31% in premature fetuses III-grade). In 74.65% of the cases was outlet forceps
      and 25.35% was low forceps. CONCLUSIONS: Forceps remains an irreplaceable tool
      for operative vaginal birth, but there is a tendency to reduce its use. In
      preterm fetuses forceps is the only method for vaginal operative delivery. Today
      only outlet and low forceps have their role in modern obstetrics, but there is a
      trend to reduce the incidence of the rotational forceps in comparison to increase
      of the use of outlet forceps.

PMID- 22479890
TI  - [Some aspects of maternal mortality in Bulgaria].
AB  - The author discusses the world and bulgarian maternal mortality rates and
      suggests the creation of obligatory diagnostical and therapeutical guidelines in
      urgent obstetrical cases.

PMID- 22479891
TI  - [Neonatal dead and method of delivery < or = 32 weeks of gestation].
AB  - The purpose of this study is to determine the dependence of neonatal dead by
      method of delivery at prematurity. MATERIAL AND METHODS: Prospective study on 238
      single births from 25-32 g.w. According to the method of delivery and fetal
      presentation newborns are divided into the following groups: vertex presentation 
      vaginal birth (PN) and Cesarean section (SC) and breech presentation - PN and
      SC. RESULTS: For the period, in the first 28 days after birth died 42 (17,7%)
      infants and 196 (82,3%) were survivors. Depending on the mode of birth
      statistically significant difference in the incidence of death after birth is not
      found in vertex presenting newborns (25% CS vs. 16,5% PN; p > 0.05). Unlike in
      breech presenting fetuses, vaginal birth < or = 32 weeks increases more than
      twofold neonatal dead compared with CS (20% vs. 7,7%; p < 0.05). Unfavourable
      outcome in CS is strongly associated with fetal presentation - three times higher
      neonatal dead in vertex presenting group (25% vs. 7, 7%; p < 0.05), as a result
      of higher incidence of absolute fetal indications (68,1% vs. 43,2%; p< 0.05).
      CONCLUSION: The way of birth doesn't affect the frequency of dead within the
      first 28 days of life in vertex presenting fetuses. Vaginal breech delivery is a
      risk factor for unfavourable neonatal outcome < or = 32 w.g. Survival in CS is
      dependent on both fetal presentation and obstetric complications, requiring
      operation.

PMID- 22479892
TI  - [Antenatal ambroxol administration for prevention of respiratopry distress
      syndrome in preterm infants: preliminary report].
AB  - The rate of preterm births has remained unchanged for the recent years despite of
      the persistent attempts to diminish it. Preterm births are responsible for about
      70% of neonatal morbidity and mortality. One of the main problems of preterm
      newborns is their lung immaturity. The aim of this study is to assess the effect
      of Ambroxol, given prenatally on the rate and severity of neonatal respiratory
      distress syndrome (NRDS) in preterm infants and its potential to replace the
      corticosteroid prophylaxis in cases where steroids are contraindicated or
      undesirable. MATERIALS AND METHODS: The trial consisted of 33 pregnant women
      between 27 and 32 week of gestation. 17 of them represented our work group and
      were given Ambroxol syrup 15 mg/ml, per os 30 ml in three intakes, for 7 days. 16
      were controls and were not given any kind of NRDS prophylaxis. RESULTS: severe
      NRDS was diagnosed in 2.5 times more cases in the control group compared to the
      work group. All infants in the control group had clinical signs of NRDS, while
      23.5% of the infants in the work group were asymptomatic. Bronchopulmonary
      dysplasia was diagnosed in 25% of the infants in the control group, compared to
      none diagnosed in the work group. Newborns with no antenatal NRDS prophylaxis had
      to be kept in intensive care units for an average period of time twice longer
      than the newborns to mothers who had received Ambroxol. CONCLUSIONS: Antenatal
      Ambroxol administration diminishes the rate of NRDS, decreases the duration,
      scope and price of the intensive care, lessens the duration of assisted
      ventilation and oxygen needs and hence improves the long-term outcome. Ambroxol
      and steroids have cumulative effect on fetal lung maturation and therefore should
      both be a part of the preterm delivery therapeutic scheme.

PMID- 22479893
TI  - [Characteristics of the severe fetalanomalies terminated in general obstetrics
      department for 4,5 years period].
AB  - The most common reason for interruption in second trimester is: Foetus mortus,
      malformations, severe intrauterine retardation, oligohydramnios, PPOM, cervical
      insufficiency, incomplete abortion. The aim of this study was to evaluate and
      analyze the distribution of incidence and type of severe fetal malformations,
      terminated at the end of first and second trimester in General obstetrical
      department in University hospital "Maichin dom"- Sofia for a period of 4 years
      and 5 months - retrospectively and prospectively. RESULTS AND DISCUSSION:
      Patients were aged between 16 and 42 years. The termination of pregnancies was in
      gestational period between 11.5 and 28 weeks. The study period is from the
      beginning of 2007 until May 2011. In the department have been terminated a total
      number of 907 pregnancies, 219 cases in second trimester and 61 of them due to
      fetal malformation, diagnozed between 11.5 to 28 weeks The incidence of fetal
      abnormalities was 27.8% (61 cases) of all terminated pregnancies in second
      trimester (219 cases). The results showed the highest rate of malformations in
      the age group 21-35 years - 62.3%. The highest percentage of malformations are in
      gestational age: 18-22 weeks - 59%. The highest incidence are as followed: neural
      tube defects (24.59%) and central nervous system (21.29%), followed by
      chromosomal defects confirmed by amniocentesis (11.47%), cardiac defects (9.83%),
      facial clefts (6.54%). The most common gestational age in which the anomalies are
      diagnosed and terminated is 18-22 weeks. The upper limit for termination of
      pregnancy on legislation is 22 weeks (globally 22-24 weeks). Ethical and social
      considerations in all cases of severe abnormalities and possible variations in
      physical and mental and intellectual development of the infant are discussed,
      these pregnancies, either diagnosed late and/or after karyotiping require
      termination of the pregnancy in late pregnancy

PMID- 22479894
TI  - [Diagnosis and prevention of neural tube defects--where are we? (Data based on
      the registry of congenital anomalies in the Pleven region)].
AB  - AIMS: to present some clinical and epidemiological data, concerning diagnosis and
      prevention of neural tube defects (NTDs), based on the registry of congenital
      anomalies (CAs) in the Pleven region; to analyse our data comparing with the data
      of other registries in Europe. MATERIALS AND METHODS: The source of the data was
      the regional population-based registry of Cas (in live births, stillbirths and
      terminations of pregnancy following prenatal diagnosis) using criteria according
      to EUROCAT recommendations. During the study period 1988-2006, 47 622 births were
      surveyed in the University hospital, City of Pleven. RESULTS: A total of 107
      cases of NTDs were ascertained. About 20% of the cases with isolated NTDs were in
      terminations of pregnancy following prenatal diagnosis, in 80% of the case the
      diagnosis was ascertained in liveborn and stillborn fetus. The isolated NTDs were
      among the most common CAs, with a proportion of 8% of all registered cases and a
      prevalence of 2 per 1000 births. The genetic counseling revealed familial data
      (other affected child/pregnancy) in 7% of families with NTDs. Prenatal diagnosis
      was provided to the subsequent risk pregnancies in the affected families and NTDs
      were detected in 7% of the pregnancies. CONCLUSION: Neural tube defects are a
      common type of congenital defects that demonstrated a relatively high prevalence
      in the Pleven region. The data of the study indicates that there is a need to
      develop an official government policy regarding prevention of NTDs
      (pericoceptional folic acid supplementation and antenatal screening of CAs).

PMID- 22479895
TI  - [Midtrimester pregnancy termination--contemporary methods and techniques.
      Review].
AB  - The improvement in the diagnostic procedures for early detection of fetal
      abnormalities has led to an increase in the number of induced mid-trimester
      pregnancy terminations. Hence, the total number of pregnancies terminated in the
      second trimester comprises somewhere between 10 and 15% of all terminations, but
      they are responsible for 2/3 of the complications and half of the deaths. These
      simple facts draw our attention to the procedure. There are two main types of mid
      trimester termination- surgical and medical. Surgical methods require special
      skills and qualification, while medical methods are considered safer and are more
      common. The latter group includes Oxytocin i.v., prostaglandin preparations Pg
      E2, Pg F2alpha, Pg E1 and their synthetic analogues, antiprogesteron drugs and
      etc. We have reviewed Bulgarian and foreign scientific resources and articles. We
      have outlined the recommendations of The Royal College of Obstetricians and
      Gynaecologists and William's Obstetrics. Also we have cited some relevant trials
      and we have made a short review of the available on the Bulgarian market
      prostaglandin preparations for mid-trimester pregnancy termination.

PMID- 22479896
TI  - [Pregnancy and malignant diseases. Part II--cervical cancer].
AB  - The malignancies of the uterine cervix are the most common neoplasia during
      pregnancy. Cancer in situ varies from 0, 11 to 0, 55% and invasive cervical
      cancer is found in around 0, 03% of pregnant women. The summarized data by
      different authors shows that the cervical cancer can be found in the wide range
      between 1:250 to 1:13000 pregnancies (mean 1:2000 to 1:3000). The specific
      characteristics of the clinical course, diagnostics and treatment approaches in
      cases with cervical cancer during pregnancy are presented. The way of delivery,
      the outcome for the fetus and the results of the treatment in these cases are
      discussed.

PMID- 22479897
TI  - [Comparative assessment of the methods of treatment of Condylomata acuminata].
AB  - The treatment of Condylomata acuminata often causes disappointment to both the
      physician and the patient since most of the current medical approaches require
      multiple examines while on the other hand success rates are low and recurrence
      rates remain high. The treatment approaches include surgical as well as non
      surgical methods. The non-surgical treatment includes the application of local
      agents such as imiquimod, podophyllotoxin, and 5-fluorouracil. Other local
      agents, used in outpatient treatment settings, include trichloroacetic acid
      (TCA), podophyllin, or the intralesional application of agents such as interferon
      and bleomycin. The surgical methods include cryotherapy, electrosurgery, excision
      and laser therapy. Their major goal is the removal of the visible lesions. The
      development of the laser systems and the new HPV vaccines are a significant
      progress in the treatment and prevention of the HPV infections.

PMID- 22479898
TI  - [Female with severe multiorgan damage and algetic myoma utery].
AB  - Painfull myoma utery in a patient with poor health condition and many
      disfunctional organs: Diabetes mellitus, Chronic renal insufficiency Gr. III
      (most probably a result of compression of the ureters causing bilateral
      hydronephrosis), arterial hypertony, anemia. The authors introduce their
      therapeutic model and manage to perform successfull operation after stabilizing
      the patient and intensive postoperative care. They point out the team work and
      good synchronization between the hospital divisions as crucial for the success of
      the treatment.

PMID- 22479899
TI  - [Angioleiomyoma utery in a female patient with damaged health condition.
      Diagnostic and terapeutic difficulties].
AB  - 35 years old patient with many health problems, on a haemodialysis and a big
      abdominal tumor originating from the pelvis. The authors share their clinical
      approach and their diagnostic and terapeutic difficulties in this case and refer
      to one of their previous publications.

PMID- 22479900
TI  - Assessment of admissions policies for veteran corpsmen and medics applying to
      physician assistant educational programs.
AB  - PURPOSE: The purpose of this study was to assess the admission policies,
      experiences, and attitudes of physician assistant (PA) program directors with
      regard to recruiting, admitting, and training veteran corpsmen and medics.
      METHODS: A descriptive survey consisting of 18 questions was distributed to all
      154 PA program directors in the United States. RESULTS: One hundred ten (71.4%)
      program directors participated in the survey. Veterans were admitted into 83.6%
      of programs in the years 2008-2010, and accounted for an average of 2.6% of all
      students. A minority of PA programs accepted college credits earned by veterans
      for their military training (45.3%) or for their off-duty education (28.4%). Few
      PA programs participated in the Yellow Ribbon Program (16%) or actively recruited
      veterans (16%). Over half of PA programs (56.7%) would be more likely to give
      special consideration to the admission of veteran corpsmen and medics if it was
      easier to equate their military education and experience to the program's
      admission prerequisites. The most frequently reported benefits for educating
      veteran corpsmen and medics in PA programs are their health care and life
      experiences, maturity, and motivation. Barriers for educating veterans include
      veterans' lack of academic preparedness for graduate education, a lack of
      time/access for recruiting, and the cost of PA school. CONCLUSION: Most PA
      program directors cited multiple benefits for educating veteran corpsmen and
      medics, but veterans face barriers for admission into PA programs. Approaches are
      discussed for facilitating the transition of corpsmen and medics from the
      military to careers as PAs.

PMID- 22479901
TI  - The effect of early geriatric exposure upon career development and subspecialty
      selection among physician assistant students.
AB  - PURPOSE: The elderly population is increasing. So too is the demand for geriatric
      medical care. Currently, there are too few practitioners to meet the expanding
      need for geriatric health services. Physician assistants (PAs) can help bridge
      this gap. METHODS: A descriptive, quantitative study assessing PA students of
      five Pennsylvania programs and their level of geriatric training and subsequent
      career specialty selection was conducted. The study consisted of a 10-question
      survey regarding student exposure to geriatric patients, type of exposure, and
      career plans. RESULTS: The study concluded that although the majority indicated
      both geriatric coursework (61.9%) and clinical exposure (54.2%) to geriatric
      patients in the first year of training, Pennsylvania PA students expressed little
      interest in specializing in geriatric medicine. CONCLUSION: Present findings
      indicate current geriatric curricula and exposure of PA students to the elderly
      may be inadequate to influence PA students in northeastern Pennsylvania to choose
      to specialize in geriatric medicine. Further research and findings from this
      study indicate using a multifaceted approach to geriatric education including
      more frequent positive interactions with elderly patients, and enhancing
      geriatric clinical exposure may result in increased interest of PA students in
      geriatric medicine. Additionally, the provision of a financial incentive may
      influence current PA students to more strongly consider a practice in geriatrics.
      These changes could potentially help increase the number of PAs interested in
      geriatrics as a career choice and facilitate PAs filling the anticipated gap
      between elderly medical needs and available health care providers.

PMID- 22479902
TI  - Physician assistant program characteristics and faculty credentials on physician
      assistant national certifying exam pass rates.
AB  - PURPOSE: Determination of the ideal terminal degree for physician assistants
      (PAs) and academic preparedness of PA educators have received much attention in
      recent years. This investigation, completed in 2009, sought to describe the
      current state of PA training programs, specifically regarding Carnegie
      classification, percent conferring master's degrees, number of full-time faculty,
      percent of faculty--both principal and other full-time faculty--with doctoral
      degrees, student-to-faculty ratio, and first-time graduate Physician Assistant
      National Certifying Exam (PANCE) pass rates. A secondary aim was to determine if
      any of these variables predict PANCE pass rates. METHODS: This study combined
      existing data obtained from multiple Internet resources including PA program
      websites and the PAEA Faculty Directory to determine the number of faculty,
      faculty credentials, number of students, and PANCE reports. Faculty members were
      categorized by highest degree attained. Linear regression was used to examine
      whether any of the programmatic variables were significant predictors of PANCE
      pass rates. RESULTS: Two of four predictors were significant--whether the program
      conferred a master's degree (Beta = 0.54, t = 7.25, P = .001) and student-to
      faculty ratio (Beta = -0.21, t = 2.63, P = .01). Mean number of full-time faculty
      per training program was eight (SD = 4, range = 2-36). The mean percent of full
      time faculty members with doctorates per training program was 17.6% (SD = 17.7%,
      range = 0-80%). CONCLUSIONS: These results, if replicated, suggest that if a
      program is seeking to increase its student performance on the PANCE, it may be
      more helpful to focus resources on improving student-to-faculty ratio, regardless
      of whether or not the faculty are doctoral level.

PMID- 22479904
TI  - Factors that influence physician assistant program graduates to choose rural
      medicine practice.
AB  - PURPOSE: A shortage of primary care, rural practitioners exists in the United
      States. The increasing number of physician assistants (PA) in the workforce could
      be an important resource in improving access to primary care services for rural
      patients, yet little is known about the specific factors influencing a PA to
      choose to practice rural medicine. The purpose of this study is to examine the
      factors that influence PA program graduates to choose rural medicine. METHODS:
      This descriptive study was conducted by electronic survey. Participants were
      recruited from the membership of the Texas Academy of Physician Assistants
      (TAPA). Main outcome measures were the correlations between rural clerkships,
      rural background, and rural practice. Participants were also queried regarding 16
      additional factors that might influence practice choice. RESULTS: A relationship
      exists between rural background and rural practice choice (chi2(4) = 16.08, P =
      .003). Correlation also was identified between completion of rural clerkships and
      rural practice choice (chi2(1) = 10.67, P= .001). Factors found to have the most
      influence on PAs to choose rural practice were (1) desire to serve the needs of
      the community; (2) type of practice; and (3) supervising physician
      characteristics. CONCLUSIONS: PAs with a rural background and those that
      completed rural clerkships have a greater propensity toward rural practice after
      graduation. It is possible, for programs with an interest or a mission of
      increasing the number of their graduates who choose rural practice, that
      knowledge of factors that influence their graduates' practice choices may prove
      beneficial.

PMID- 22479903
TI  - An educational strategy for using physician assistant students to provide health
      promotion education to community adolescents.
AB  - PURPOSE: The "Competencies for the Physician Assistant Profession" identify core
      competencies that physician assistants (PAs) are expected to acquire and maintain
      throughout their career (see
      http://www.nccpa.net/pdfs/Definition%20of%20PA%20Competencies%
      203.5%20for%20Publication.pdf). Two categories of competencies relate to patient
      care and interpersonal and communication skills and articulate the need for PAs
      to be effective communicators and patient educators. The value of a health
      education curriculum for the adolescent population has been recognized since the
      early 1900s. PA student-designed health promotion presentations aimed at the
      adolescent population are an innovative educational strategy involving students
      in community education. METHODS: PA student-designed presentations based upon
      previously identified topics were presented in the community. Students presented
      topics including Smoking Cessation, The Effects of Drugs and Alcohol, Self
      Esteem, and others to adolescents. Community audiences were varied and included
      alternative high schools and teens within the Department of Youth Corrections
      facilities. RESULTS: PA students created 17 portable presentations for community
      adolescents. Two hundred sixty-eight students gave presentations to more than 700
      adolescents ranging from 11-22 years of age between the years 2005-2010. Eighty
      two percent (646/791) of adolescent participants either strongly agreed or agreed
      that they learned at least one new piece of information from the presentations.
      Sixty percent (12/20) of community leaders requested that the PA students return
      to give additional health promotion presentations. Analysis of comments by PA
      students revealed that 98% of students found the experience beneficial. Students
      identified the experience as helping them better understand how to design
      presentations to meet the needs of their audience, feel more comfortable with
      adolescents, and gain confidence in communicating. Seventy-five percent stated
      they would continue to be involved in community education because of the
      experience. CONCLUSIONS: These presentations serve to enrich student professional
      development, enhance community awareness of the PA profession, and provide
      educational information to adolescent populations, many of whom are considered at
      risk. In addition, this model serves to enhance the service-learning curriculum.

PMID- 22479905
TI  - Should you join a nonprofit board? Investigate before you make a decision. Part 2
      of 2.

PMID- 22479906
TI  - Evidence-based medicine: its roots and its fruits.

PMID- 22479907
TI  - Postgraduate clinical education of physician assistants.
AB  - PURPOSE: Physician assistant (PA) postgraduate clinical training programs have
      existed since 1971. There are anecdotal reports of increasing numbers of programs
      available in the United States, although a reliable means of identifying and
      tracking such programs has not been available. The purpose of this study was to
      describe the current state of postgraduate, clinical educational programs for PAs
      based on defined criteria for study inclusion and to propose the use of these
      criteria for use by future investigators to determine trends in program
      development. METHODS: All programs potentially meeting the study criteria for
      postgraduate PA clinical programs, including programs actively enrolling PAs and
      that provide didactic and clinical instruction of 6 or more months duration, were
      contacted to participate in an online survey. RESULTS: A total of 49 programs (42
      nonmilitary) programs were included with 22 nonmilitary programs opening for
      enrollment in or after 2008. Most programs enrolled one or two PAs annually. All
      respondents of nonmilitary programs indicated that a certificate of completion
      was provided and no academic credit or degree was offered. A variety of didactic
      and clinical instructional methods were used. Most sites also provided clinical
      rotations for PA students, and many required PA residents to participate in
      student teaching. Although few programs have been accredited by the Accreditation
      Review Commission on Education for the Physician Assistant (ARC-PA), most
      programs are pursuing, or plan to apply for, accreditation. CONCLUSIONS: The
      results of this survey provide an up-to-date report on the status of PA
      postgraduate clinical training programs. The investigators recommend future
      studies use the same criteria for inclusion to establish future trends in program
      development.

PMID- 22479908
TI  - Functional importance of estrogen receptors in the periodontium.
AB  - The main functions of estrogen are associated with reproduction. However,
      estrogen has been shown to be of functional importance also in non-classic target
      organs. Previous studies, especially epidemiologic and clinical ones, have
      addressed estrogen's influence on periodontitis, suggesting that estrogen has a
      beneficial effect, but the biological mechanisms have not been identified.
      Estrogen exerts genomic effects in the target cells by binding to the nuclear
      receptors, estrogen receptor (ERs), ERalpha and ERbeta. The expression of the two
      subtypes of ERs varies depending on the tissue. The overall objectives of this
      thesis were to study the functional importance of estrogen receptors in the
      periodontium with special focus on inflammation, and stimulators of inflammation
      and their signaling pathways. The thesis is based on the following five papers.
      In Paper I, effects of estrogen on E. coli LPS-induced PDL cell production of
      interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and C-reactive
      protein (CRP) are assessed, by using ELISA. Furthermore, effects of LPS and
      estrogen on the normal characteristics of the PDL cell such as collagen synthesis
      and cell proliferation is determined by using L-[3H]proline incorporation and
      measurement of DNA synthesis, respectively. KEY FINDINGS: E. coli LPS stimulates
      PDL cell IL-6 and MCP-1 production but has no effect on the normal physiological
      properties of PDL cells. LPS-induced IL-6 and MCP-1 is not reversed by estrogen
      suggesting that estrogen has no anti-inflammatory effect in these experiments. In
      Paper II, we investigate the effects of ovariectomy and aging on tooth attachment
      in female mice by using morphometric analysis. KEY FINDINGS: Withdrawal of female
      sex hormone production by ovariectomy has no effect on alveolar bone height and
      apical termination of the junctional epithelium. In a second series of
      experiments these parameters are similar in mice sacrificed at 8-26 weeks of age,
      suggesting that tooth attachment is preserved with age in mice within a period of
      six months. In Paper III, the objective is to investigate the regulation of
      CCL2/MCP-1, CCL3/MIP-1alpha, and CCL5/RANTES chemokines by estrogen in human PDL
      cells by determining mRNA transcript levels (using quantitative real-time PCR)
      and protein levels (using ELISA). KEY FINDINGS: A physiological concentration of
      estrogen reduces the expression of CCL3 mRNA by about 40% compared to PDL cells
      treated with LPS alone. In contrast, inter-individual differences in the effects
      of estrogen on CCL5 mRNA expression are observed. These findings indicate that
      estrogen affects chemokine expression in PDL cells showing a complex pattern
      involving down-regulation as well as up-regulation of chemokines. Estrogen exerts
      both anti-inflammatory and pro-inflammatory effects through these mechanisms. In
      Paper IV, ER expression in human gingival biopsies, and effects of estrogen on
      cultured gingival epithelial cell (HGEP) proliferation, are investigated.
      Expression of ERalpha and ERbeta is determined by immunohistochemistry and
      effects of estrogen on HGEP proliferation monitored by measuring DNA synthesis.
      KEY FINDINGS: HGEP cells show strong ERbeta immunoreactivity but low ERalpha
      immunoreactivity both in vivo and in culture, suggesting that ERbeta is the
      predominant ER subtype in HGEP. High, but not low, concentrations of estrogen
      attenuates proliferation of gingival epithelial cells, indicating a concentration
      dependent mechanism. In Paper V, the objective is to investigate the effects of
      LPS from Escherichia coli and Porphyromonas gingivalis on IL-6 production in
      human PDL cells and endothelial cells, and the signaling mechanisms involved.
      Quantitative real-time PCR is used to determine IL-6 mRNA levels and ELISA to
      determine IL-6 protein. KEY FINDINGS: E. coli LPS (but not P. gingivalis LPS)
      stimulates IL-6 production in PDL cells. Treatment with the non-selective nitric
      oxide synthase inhibitor L-NAME reduces IL-6 by 30%, while aminoguanidine, an
      inhibitor of inducible nitric oxide synthase, does not affect IL-6 levels,
      showing a mechanism probably involving nitric oxide formation via endothelial
      nitric oxide synthase. Treatment with the glucocorticoid steroid dexamethasone
      totally prevents-E. coli LPS-induced IL-6 in PDL cells.

PMID- 22479909
TI  - The importance of a military-unique curriculum in active duty graduate medical
      education.
AB  - Military residency training programs are unique in a number of ways, none more
      significant than the fact that our graduates become our colleagues and future
      teammates on lengthy deployments. We have a fundamental responsibility to make
      sure that they are up to the task. Although certainly not a panacea, a well
      crafted military-unique curriculum goes a long way toward creating the kind of
      institutional culture and training mindset that enables a successful transition
      from active duty resident to deployable physician.

PMID- 22479910
TI  - Influenza and wound infections: laboratory support for deployed U.S. forces.
AB  - Since 1997, the absence of a global, DoD public health laboratory system has been
      identified as a vulnerability in the U.S. military's effort to identify and
      quickly respond to emerging infections. The AFHSC Division of GEIS Operations has
      attempted to mitigate this vulnerability by supporting initiatives such as the
      DoD Global Influenza Surveillance Program and the DoD Directory of Public Health
      Laboratory Services. AFHSC continues to be engaged in identifying and addressing
      diagnostics needed to protect deployed forces. The GASI and the enhanced
      capability for identification of MDROs and threatening influenza strains in
      deployed areas are recent examples of GEIS utilizing its financial resources and
      position as a DoD organization to coordinate the efforts of the military services
      and other U.S. government organizations to improve preparedness for EID agents.
      However, the absence of a defined, comprehensive public health system that
      contains surveillance systems, reference laboratories, and public health
      communication systems functioning in unison to provide reach back and reference
      laboratory support to the global MHS remains a significant gap.

PMID- 22479911
TI  - Effects of military deployment on cognitive functioning.
AB  - Military deployment poses many risks for cognitive functioning. When deployed
      individuals are compared to a nondeployed control group, there is some evidence
      that deployment may be associated with declines in cognitive functioning. The
      current study examined cognitive performance before and following deployment in a
      large sample of active duty military personnel (N = 8002) who reported no
      traumatic brain injury (TBI). Cognition was assessed using the Automated
      Neuropsychological Assessment Metrics version 4 TBI Military (ANAM4 TBI-MIL)
      battery, a computer-based battery of tests measuring attention, processing speed,
      and general cognitive efficiency. Pre- and postdeployment scores were compared
      using repeated measures analyses. Although statistically significant differences
      were observed for all tests (with 5 of 7 tests demonstrating performance
      improvement), effect sizes were very small for all but 1 test, indicating that
      performance differences had minimal clinical significance. Likewise,
      determination of change for individuals using reliable change indices revealed
      that a very small percentage (<3%) of this presumed healthy sample showed
      meaningful decline in cognition following deployment. Analyses indicated that
      despite risks for cognitive decline while in theater, deployment had minimal to
      no lasting effect on cognition as measured by ANAM4 TBI-Mil upon return from
      deployment.

PMID- 22479912
TI  - Automated Neuropsychological Assessment Metrics (v4) Traumatic Brain Injury
      Battery: military normative data.
AB  - The aim of the present study was to establish normative data for the Automated
      Neuropsychological Assessment Metrics (v4) Traumatic Brain Injury (ANAM4 TBI)
      battery in a military context. ANAM4 data from over 107,500 active duty service
      members ranging from 17 to 65 years of age were included in this study. The
      influence of the demographic variables of age and gender were also examined.
      These norms, stratified by age and gender, represent a more comprehensive set of
      norms than previously available and are provided as a representative set of norms
      for clinical practice. Additionally, base rates of below average performance in a
      normal population are provided to help inform clinical decision making.

PMID- 22479914
TI  - Factors affecting mental health service utilization among deployed military
      personnel.
AB  - This study contrasts the characteristics of clients using military mental health
      services in deployed and nondeployed settings, the communications between their
      mental health providers and commanders, and the impact of mental health services
      on their military duties. The study explored the rates of command communication
      and duty restrictions across settings and referral sources. The study used
      secondary data from two predominantly Air Force sources: (1) deployed data
      collected in 2005 at Al Udeid Air Base, Qatar; and (2) nondeployed data collected
      in 2001 at various nondeployed settings. Chi2 analyses were used to compare the
      demographic variables, command communication, and duty restrictions. Among self
      referrals, there were higher rates of command communication and duty restrictions
      in the deployed setting. Further analysis found that the rate of self-referral to
      mental health services did not vary significantly across settings despite the
      barriers of increased command communications and duty restrictions in the
      deployed setting. This study extends the findings of Rowan and Campise's 2006
      initial nondeployed study into the deployed environment.

PMID- 22479913
TI  - Training, deployment preparation, and combat experiences of deployed health care
      personnel: key findings from deployed U.S. Army combat medics assigned to line
      units.
AB  - OBJECTIVE: To describe the perceptions of training and deployment preparation and
      combat experiences and exposures of U.S. Army combat medics. METHODS: Data were
      from the first year of a 3-year longitudinal study designed to assess the impact
      of combat on the behavioral health and resilience of 347 combat medics surveyed 3
      to 6 months after returning from a 12-month deployment to Operation Enduring
      Freedom/Operation Iraqi Freedom theatre and assigned to brigade combat teams.
      RESULTS: Analyses indicated that combat medics may benefit from better
      preparation in types of shifts required during deployment, type and intensity of
      combat likely to be seen and experienced, more adequate training in the area of
      stress and mental health care management, and easier access to behavioral mental
      health care. CONCLUSIONS: The military has shown considerable progress in
      addressing and understanding the mental health care needs of Soldiers. However,
      challenges remain. Additional emphasis should be placed on reducing the stigma
      and barriers related to mental health care both in theatre and garrison and on
      developing an evidence-based, validated program for medics and other Soldiers to
      recognize stress and mental health issues on the battlefield. For medics, this
      should be from two perspectives-that of a combat Soldier and that of a medical
      provider.

PMID- 22479915
TI  - Web-based post-traumatic stress disorder education for military family members.
AB  - OBJECTIVE: Since post-traumatic stress disorder (PTSD) is common after military
      deployment and affects both military service members and their families, we
      sought to both improve PTSD-related knowledge of military family members and to
      foster actions to help service members with their symptoms. METHODS: Focus groups
      were conducted with military family members and their feedback was incorporated
      into an educational Web site to improve family members' knowledge of PTSD. We
      pilot-tested the site and a 25-item questionnaire, then used it to assess the
      knowledge of 497 family members before and after their use of the Web site.
      RESULTS: Use of this educational Web site improved military family members' PTSD
      related knowledge on a 25-item test, with an increase from a mean 13.9 correct
      responses beforehand to 18.7 after Web site use (p < 0.001; effect size 1.2). In
      addition, 217 family members returned to the site > or =10 days after their
      initial visit; 57% had taken actions such as discussing the service member's
      symptoms with them or persuading them to get medical attention, and 82 to 95% of
      them believed their actions to be beneficial. CONCLUSION: A Web-based
      intervention can both improve PTSD-related knowledge and foster behavioral
      changes in military family members.

PMID- 22479916
TI  - Using pictograms for communication.
AB  - The U.S. Navy sponsors annual Pacific Partnership deployments to provide
      humanitarian and disaster relief training for the U.S. military, partner nations,
      nongovernmental organizations, and host nations. Communication between these
      groups and the local populations receiving medical care is problematic in that
      sufficient numbers of capable translators are often unavailable or vastly
      undertrained with respect to medical terminology and practice. In addition,
      should Pacific Partnership respond to a real disaster, adequate numbers of
      translators will likely be unavailable as a result of the disaster itself.
      Consequently, medical providers will require alternate methods of communication
      previously tested for efficacy and validity. One such method is the use of
      pictograms designed to represent common medical maladies. To determine whether
      pictograms meet the 85% congruence level required by the American National
      Standards Institute, 36 images were provided to English-speaking physician
      assistants and nurse practitioners for interpretation with three images repeated
      within the array to assess internal validity of the questionnaire. Of the 33
      distinct images, 26 (79%) reached 85% congruence showing that validated images
      may be a method of communication in circumstances where medical providers and
      patients speak discordant languages.

PMID- 22479917
TI  - Foreign health sector capacity building and the U.S. military.
AB  - The U.S. joint military medical community has an increasing role in collaborative
      health sector engagement internationally as part of a whole of government
      approach to successful operations. The military must master the ability to
      catalyze health sector gains that can be developed by hosts, U.S. Government, and
      international agencies in both permissive environments and conflict zones.
      Capacity building is helping a partner develop their own capabilities, standards,
      and resources to the point of self-sufficiency. Optimal effects will come through
      understanding the military and civilian health sectors of nations and regions,
      grasping the importance of health to stability and security, and integrating
      efforts with global health initiatives. The goal is to cultivate military and
      civilian relationships that assist host nation-led sustainable health sector
      effects that result in enduring positive U.S. national security outcomes.

PMID- 22479918
TI  - Indicators of sequential fitness assessment failures for Travis Air Force Base
      airmen who attend the Be Well Course.
AB  - PURPOSE: This retrospective community intervention trial evaluated the Be Well
      course--a mandatory lifestyle intervention course for airmen who fail the U.S.
      Air Force fitness assessment (FA)--at Travis Air Force Base from November 1, 2010
      to February 1, 2011. METHODS: Pre-existing data (N = 276) were analyzed for
      change in FA scores and for predictors of future outcomes. RESULTS: On the
      subsequent FA after completing Be Well, males and females scored significantly
      higher on total points, aerobic fitness, push-ups, and sit-ups (p < 0.001 for
      all), and males had lower body mass indices (BMI; p = 0.005) and smaller
      abdominal circumferences (AC; p < 0.001), as compared to their initial FA. As
      opposed to those who passed the subsequent FA, those who failed consecutively had
      significantly higher BMIs (p < 0.001), larger ACs (p < 0.001), and lower total
      scores (p < 0.0001) at the time of the initial failure. CONCLUSIONS: The Be Well
      course is an effective tool and should remain a component of remedial training
      for airmen who fail the Air Force FA. Stratification of failure should be
      considered at the policy level, with special consideration given to the risk
      factors of high BMI, large AC, and low total FA score.

PMID- 22479919
TI  - Multidisciplinary intervention with sibutramine: assessing successful weight loss
      predictors in military adolescent dependents.
AB  - OBJECTIVES: Assess body mass index (BMI) reduction through a multidisciplinary
      intervention with sibutramine in adolescents of military parents and examine
      characteristics and behavioral traits as predictors of successful weight loss.
      METHODS: A prospective study where participants received sibutramine daily for 6
      months. Adolescents ages 12 to 18 with BMI-for-age and sex greater than 95
      percentile and good health were enrolled. Outcome variables are BMI, biochemical
      indices, and clinical measurements. Predictor variables are participant
      demographics, family history, lifestyle changes, and behavioral traits assessed
      with behavioral assessment for children. RESULTS: One hundred participants were
      recruited with 81% completion. In those participants who completed the 6-month
      intervention, a mean participant BMI reduction of 3.1 kg/m2 (-9.3%) (p < 0.001;
      95% CI: -10.5% to -7.9%) was obtained with 79% successfully meeting the weight
      loss goal. Sibutramine dose was increased from 10 to 15 mg at 3 months for
      participant with <2.5% BMI reduction from baseline. Sibutramine dose at 3 months
      (p < 0.001) and participants perception of relationship with parents (p = 0.05)
      were statistically significant predictors of successful weight loss (> or =10%
      reduction in BMI). CONCLUSIONS: Sibutramine was effective at promoting minimum
      beneficial BMI reduction of 5% in adolescents with service-connected parents;
      however, increasing dosage at 3 months did not improve the likelihood of being
      successful.

PMID- 22479920
TI  - Early onset pneumonia following pulmonary contusion: the case of Stonewall
      Jackson.
AB  - Confederate Lieutenant General Thomas J. "Stonewall" Jackson was wounded by his
      own men at the Battle of Chancellorsville during the American Civil War. While
      being removed from the field, Jackson fell from the litter and struck the right
      side of his chest on a large stone or stump. Four days following the amputation
      of his left arm, Jackson developed pneumonia in his right lung. His treating
      physicians believed the infection developed secondary to a pulmonary contusion
      that occurred when he fell from the litter. Pulmonary contusions are an
      independent risk factor in the development of post-traumatic pneumonia and an
      infection that occurs within 72 to 96 hours of injury is termed an early onset
      pneumonia. The nature and timing of Stonewall Jackson's illness following his
      wounding is consistent with the modem diagnosis of early onset pneumonia
      following chest trauma.

PMID- 22479921
TI  - Broad exposure screening of air pollutants in the occupational environment of
      Swedish soldiers deployed in Afghanistan.
AB  - The main objective of this study was to perform an initial characterization of
      Swedish soldiers' exposure to air pollutants in Afghanistan and screen for
      potential health hazards. Stationary monitoring was performed in two military
      camps, International Security Assistance Force Headquarters in Kabul and Camp
      Northern Lights in Mazar-e Sharif, at both outdoor and indoor locations. A broad
      screening including particulate matter (PM10 and PM2.5), polycyclic aromatic
      hydrocarbons (PAHs), oxygenated PAHs, n-alkanes, nitrogen dioxide (NO2), sulfur
      dioxide, toxic metals, and volatile organic compounds (VOCs) was performed over 2
      weeks in the autumn of 2009. The results were compared to current air quality
      guidelines. Particulate matter was identified as the main potential health hazard
      since military exposure guidelines for marginal effects were exceeded outdoors.
      In addition, especially in Kabul, levels of particle-bound PAHs and oxy-PAHs were
      high, whereas levels of toxic metals were generally low. Among gaseous
      pollutants, elevated NO2 levels in Kabul supported combustion as a major
      contributor to the poor air quality. VOC levels were generally low, but levels of
      some pollutants exceeded current guidelines. Because of elevated concentrations
      of particles with a high content of toxic organics, further monitoring and
      characterization of the occupational environment are warranted.

PMID- 22479922
TI  - Gunshot and improvised explosive casualties: a report from the Spanish Role 2
      medical facility in Herat, Afghanistan.
AB  - OBJECTIVE: To provide an analysis of casualties treated during medical evacuation
      (MEDEVAC) or/and at the Spanish Role 2 in Herat, Afghanistan, including type of
      weapon, injuries, and effects of protective measures. METHOD: A retrospective
      analysis was carried out concerning patients who had suffered injuries from
      either gunshot or explosive devices treated during MEDEVAC or/and at this
      facility during the period 2005-2008. RESULTS: The total number of cases analyzed
      was 256. The majority of the casualties were produced by explosive devices (71%).
      The anatomical regions most affected were the lower limbs (48%). There was a
      higher New Injury Severity Score in casualties wounded by gunshot (14 +/- 1) than
      in those wounded by explosive devices (8.5 +/- 1.5) (p < 0.001). Surgical
      procedures for injuries caused by gunshots were 1.7 times more likely than for
      those due to explosive devices (95% confidence interval: 1.4 to 2.1). Protective
      devices were used only by 25% of casualties. CONCLUSIONS: The injury score
      indices of firearm casualties were higher than the explosive device casualties'
      injury score indices. The possible reasons for this finding are discussed.

PMID- 22479923
TI  - Origin of the 44-mm behind-armor blunt trauma standard.
AB  - A number of armed assaults on public officials occurred in the early 1970s, which
      prompted the Lightweight Soft Body Armor Program to develop modern, concealable,
      soft body armor. Methodology needed to be developed to (1) determine the
      effectiveness of the soft body armor to stop bullet penetration and (2) assess
      the potential injury from nonpenetrating blunt impacts to the body. Extensive
      research was performed under the program to develop methodologies to assess soft
      body armor, including behind-armor blunt trauma (BABT) evaluation. This
      methodology is still used today, and it has been applied extensively beyond the
      original intent. However, the origin of this methodology is not well understood
      by many researchers in the various fields in which it is being applied because
      the original documentation is difficult to obtain. Therefore, the purpose of this
      article is to provide a comprehensive review of the BABT to offer researchers
      information about its history and limitations.

PMID- 22479924
TI  - The effects of arterial blood pressure on rebleeding when BleedArrest, Celox and
      TraumaDex are used in a porcine model of lethal femoral injury.
AB  - Uncontrolled bleeding remains the leading cause of preventable death in trauma.
      Hemostatic agents are effective in hemorrhage control but often fail following
      high-volume crystalloid resuscitation. Aggressive fluid resuscitation increases
      the blood pressure which may dislodge the newly formed clot causing rebleeding.
      The purpose of this study was to determine the systolic blood pressure (SBP) and
      the mean arterial pressure (MAP) at which rebleeding occurs when a clot is formed
      by one of these hemostatic agents (BleedArrest, TraumaDex, or Celox) compared to
      a control group. This was a prospective, experimental study using male 5
      Yorkshire swine per group (BleedArrest, TraumaDex, Celox, or control). The
      femoral artery and vein were transected to simulate a traumatic injury. Subjects
      were allowed to bleed for 60 seconds then one of the agents was poured into the
      wound. The control group underwent the same procedures but without the hemostatic
      agent. After 30 minutes, dressings were removed and the SBP was increased
      incrementally using intravenous phenylephrine until rebleeding occurred or until
      the arterial blood pressure reached 210 mm/Hg. The SBP and MAP were significantly
      higher in the BleedArrest, TraumaDex, and Celox groups compared to a control
      group (p < 0.05).

PMID- 22479926
TI  - Cefazolin-induced neutropenia and thrombocytopenia following trauma: a case
      report.
AB  - Cefazolin, a first generation cephalosporin, is a rare cause of cyclical fevers,
      neutropenia, and thrombocytopenia following surgical prophylaxis. We present the
      case of an otherwise healthy 21-year-old male who sustained a 50-cm laceration to
      his chest and abdomen. He received emergency department prophylaxis with
      cefazolin and surgical repair. Subsequently, he developed cyclical fevers,
      neutropenia, and thrombocytopenia, all of which resolved after antibiotic
      discontinuation. This is the first case report in which the perioperative
      administration of cefazolin following trauma resulted in significant neutropenia
      and thrombocytopenia. Also discussed in this report are the etiology, workup, and
      treatment of cefazolin-induced neutropenia.

PMID- 22479925
TI  - Evaluation of thermotherapy for the treatment of cutaneous leishmaniasis in
      Kabul, Afghanistan: a randomized controlled trial.
AB  - Anthroponotic cutaneous leishmaniasis (CL) is a common cause of ulcerative
      lesions and disfiguring scarring among children in Afghanistan. Most lesions
      occur on the face and are commonly caused by the trypanosome protozoan parasite
      Leishmania tropica, transmitted by the bite of an infected sandfly (Phlebotomus
      sergenti). This study compared the effectiveness of a single localized treatment
      with thermotherapy to 5 days of intralesional administration of Glucantime for
      the treatment of CL. Three hundred and eighty-two patients with CL were randomly
      assigned to the two treatment groups and followed for 6 months. The cure rate for
      the thermotherapy group was 82.5%, compared to 74% in the Glucantime group. The
      authors concluded that a single localized treatment with thermotherapy was more
      effective than 5 days of intralesional administration of Glucantime.
      Additionally, thermotherapy was more cost-effective, with fewer side effects, of
      shorter duration, and with better patient compliance than intralesional
      Glucantime.

PMID- 22479927
TI  - Giant gastric ulcer: a challenging diagnosis in the deployed military
      environment.
AB  - The purpose of this article is to report on the evaluation of vague abdominal
      pain and anemia in the deployed military environment resulting in the diagnosis
      of a giant gastric ulcer. This patient's abdominal pain was initially thought to
      be attributable to a lower digestive tract process and her anemia was insidious
      in onset but progressive. A computed tomography examination was obtained.
      Circumferential gastric wall thickening, more prominent posteriorly with
      ulceration, adjacent inflammation, and perigastric lymphadenopathy suspicious for
      a malignancy or a giant gastric ulcer was identified. Referral and medical
      evacuation to a tertiary care facility out of the deployed setting resulted in an
      endoscopy showing a giant gastric ulcer with no evidence of malignancy. Prompt
      evaluation of the patient with the most expeditious radiologic imaging modality
      available at hand, rather than delayed sequential evaluation, revealed an
      uncommon finding and conceivably saved this patient's life. Close cooperation
      among appropriate specialists in the deployed setting resulted in an optimal
      outcome in a suboptimal environment.

PMID- 22479928
TI  - Unilateral mydriasis potentially associated with contact with a supplement powder
      mix.
AB  - INTRODUCTION: Dietary supplement use is common in military populations. Presented
      is a case of unilateral mydriasis from contact with a supplement mix.
      Standardized approach to mydriasis is fundamental for diagnosis. CASE: A 20-year
      old active duty Marine presented to the Emergency Department for evaluation of an
      enlarged pupil. She had no visual deficits or symptoms otherwise. She had been
      consuming increased amounts of energy drinks including a supplement powder mix
      and recalled rubbing her eye while pouring the mix that morning. Her exam
      demonstrated an asymmetric, nonreactive right pupil both directly and
      consensually with normal left pupil findings. Exam was otherwise unremarkable.
      Following unresponsiveness to pilocarpine challenges, pharmacological dilation
      was diagnosed potentially, secondary to supplement contact without absolute
      causative effect established. Two days afterward, her exam was normal.
      DISCUSSION: Several supplement mixes contain compounds with stimulant activity
      mimicking medications used for pupil dilation. Unilateral mydriasis from contact
      with anticholingeric substances has been reported, specifically Angel's Trumpet,
      ipratropium, and moonflower, but there have been no reports with supplement mix
      induced dilation. CONCLUSION: Dietary supplement use in the military is an
      overwhelming phenomenon. This unique presentation of pharmacological mydriasis
      reinforces the importance of supplement histories in our military populations for
      various health presentations.

PMID- 22479929
TI  - Hospital staff at "breaking point".

PMID- 22479930
TI  - "Nursing leaders need backing and support to reclaim care".

PMID- 22479931
TI  - "Like donkeyjackets, listening to dissenters has gone out of fashion".

PMID- 22479932
TI  - "Nurses could help stop sepsis killing four patients an hour".

PMID- 22479933
TI  - Osteoarthritis 1: Physiology, risk factors and causes of pain.
AB  - Osteoarthritis (OA) is a synovial joint disorder characterised by pain,
      stiffness, and restricted function. It is often classed as a degenerative disease
      because the affected joints deteriorate over time. This article, the first in a
      three-part series, describes the complex pathophysiology and causes of pain in
      OA, risk factors, and how it is diagnosed.

PMID- 22479934
TI  - Tackling infection in care homes.
AB  - Care home residents have a higher risk of contracting a healthcare-associated
      infection than the general population. This article describes a three-dimensional
      strategy that reduced MRSA colonisation among this group. This project won a
      Nursing Times/Health Service Journal Patient Safety Award in the primary care
      category in 2011.

PMID- 22479935
TI  - You feel that your life has been cut short.

PMID- 22479936
TI  - Identifying leadership development needs.
AB  - BACKGROUND: Nurses and midwives are expected to fulfil leadership roles at all
      levels, but efforts to support them strategically are often unfocused. AIM: To
      describe nurses' and midwives' clinical leadership development needs and their
      views on the issue. METHOD: A survey was carried out with a random sample of
      nurses and midwives (911 responses), and 22 focus groups were conducted. RESULTS:
      Leadership development need was greatest in the domain of "developing the
      profession", while it was lower in areas associated with "managing patient care".
      DISCUSSION AND CONCLUSION: As nurses and midwives move further away from direct
      care, their clinical leadership development needs increase. A number of
      recommendations are made for education and training programmes.

PMID- 22479937
TI  - Health promotion in psychosis services.
AB  - Early intervention in psychosis (EIIP) services work to detect and treat the
      condition early, which improves prognosis and saves money. This article reports
      on the impact of an EIIP team's efforts to promote health by raising awareness of
      psychosis and services available. An audit before and after health promotional
      activities showed referrals to EIIP increased by 10% and admissions to acute
      inpatient units fell by 75%.

PMID- 22479938
TI  - Mobile operator.

PMID- 22479939
TI  - Mental health.

PMID- 22479940
TI  - Time to change.

PMID- 22479941
TI  - Getting personal.

PMID- 22479942
TI  - Changing direction.

PMID- 22479943
TI  - Mind over matter?

PMID- 22479944
TI  - Working to help mental health.

PMID- 22479945
TI  - The government has issued a list of revised descriptors for PIP.

PMID- 22479946
TI  - The Spartacus report shows how people can come together to fight for disability.

PMID- 22479947
TI  - The bigger picture. Time to change.

PMID- 22479948
TI  - Important of caring for their mental as well as physical health.

PMID- 22479949
TI  - Dying to be thin. Your guide to today's mental health issues.
AB  - With increased awareness of under 12s, as well as older children, developing
      serious eating disorders there is an urgent need for early recognition and
      treatment, as Dr Agnes Ayton explains.

PMID- 22479950
TI  - Doctor's orders.

PMID- 22479951
TI  - Viewpoint. The future of NHS-provided mental health care.

PMID- 22479952
TI  - Legal eye: a parliamentary bill is challenging legal mental health
      discrimination.

PMID- 22479953
TI  - Network. BME service-user led projects.

PMID- 22479954
TI  - Does early intervention for psychosis services make economic sense?

PMID- 22479955
TI  - Feeling good.

PMID- 22479956
TI  - Looking at ordinary people's tales of living with their mental illness. Interview
      by Alita Buttress.

PMID- 22479957
TI  - A remedy for health care in 2012: collaborative leadership.

PMID- 22479958
TI  - Sadly caught up in the moment: an exploration of horizontal violence.
AB  - The behaviors associated with horizontal violence can have negative consequences
      for nurses, patients, and organizations. Participants in this study were sent a
      survey that listed nine behaviors associated with horizontal violence. They were
      asked if they had witnessed, experienced, or neither witnessed nor experienced
      the nine behaviors. Participants were also asked to respond to three open-ended
      questions intended to capture their uniquely personal experiences with horizontal
      violence. For all but one behavior, the majority of participants stated they had
      witnessed or experienced eight of the nine behaviors associated with horizontal
      violence in their workplace. In response to the findings of this study, an
      educational program was developed to assist nurses in recognizing and responding
      to horizontal violence.

PMID- 22479959
TI  - Succession planning in hospitals and the association with organizational
      performance.
AB  - Effective succession planning is the heart of leadership development and an
      essential business strategy because it enhances the ability to achieve orderly
      transitions and maintain productivity levels. The results of this study are
      consistent with previous studies that exhibit a positive association of previous
      years' performance with internal succession planning. The key to successful
      succession planning lies in building a solid foundation of profitability. Having
      successors ready to fill key vacancies helps improve operational condition and
      the bottom line, and thus, gives a competitive edge in the market. Preparing
      successors for leadership may determine which organizations simply survive and
      which thrive and lead their markets down the road.

PMID- 22479960
TI  - Effects of a short-term linguistic class on communication competence of
      international nurses: implications for practice, policy, and research.
AB  - International nurses face a host of challenges in their transition and adaptation
      to the U.S. health care environment. Language and communication barriers have
      been ranked consistently as a top concern by employers, regulatory agencies, and
      international nurses themselves. Researchers in this study examined the effects
      of a 10-week linguistic class on the reduction of phonologic errors affecting
      foreign accent in a sample of international nurses. The linguistic course
      appeared to be effective in improving the international nurses' linguistic
      competence by reducing their phonologic errors significantly. Moreover, the
      intervention narrowed the linguistic gap between international nurses from non
      English and English-speaking countries. Findings from this study have important
      implications for practice, policy, and research regarding quality of care, as
      well as for the transition, job satisfaction, and retention of international
      nurses.

PMID- 22479961
TI  - The MISSCARE Survey-Turkish: psychometric properties and findings.
AB  - One measure of the process of nursing care is missed nursing care, which refers
      to any aspect of required care that is omitted either in part or in whole or
      delayed. Little is understood about how the quality and processes of nursing care
      differs among countries around the world. The aims of this study were (a) to test
      the psychometric properties of the MISSCARE Survey-Turkish and (b) to compare the
      extent and type of missed care as well as reasons for missing care between Turkey
      and the United States. There was less missed care reported by Turkish nurses as
      compared to U.S. nurses (p < 0.0001). Turkey nurses identified more problems with
      inadequate staffing resources (p < 0.0001), materials resources (p < 0.0001), and
      communication/teamwork (p < 0.0001) as reasons for missed nursing care than did
      U.S. nurses. Missed nursing care is a critical problem that needs to be addressed
      in both countries.

PMID- 22479962
TI  - Is nurse executive/nurse management practice a profession?
AB  - The question of whether management is a profession is hotly debated by our
      colleagues in business. We should learn from that dialogue and ask ourselves the
      same question regarding nursing management. Looking at our practice against the
      commonly accepted descriptions of professional practice, the answer is probably
      no. This is an ideal time to reflect on the practice of nursing management and
      executive practice. We must examine nursing management practice and learning
      deliberately from our experience.

PMID- 22479963
TI  - The future of the Affordable Care Act: will we abandon health care reform?
AB  - With obstacles to the Affordable Care Act (ACA) growing, nurses need to continue
      to educate themselves about the ACA and the issues it is designed to address.
      While it has many shortcomings, the ACA invests in creating a new infrastructure
      that holds the potential to improve care quality and contain costs. Health
      economist Victor Fuchs suggests three areas must change if we are to have a
      health care system that is quality focused: information, infrastructure, and
      incentives. The current health care legislation is noble and lays a basis for
      future structural cost containment. The health care system continues to unravel
      as our politicians remain polarized over reform efforts. We must engage or we
      will never find solutions, never see reform.

PMID- 22479964
TI  - Through the eyes of gratitude.
AB  - There are complex considerations at play when deciding what nurse should work
      with which patient. During the course of a relationship between a patient and a
      nurse, or a nurse and a patient's family, remarkable and life-changing
      interactions can occur. The relationship between Patrick Barnes, his family, and
      the nurses who cared for them, was the inspiration for the creation of the DAISY
      Foundation. The DAISY Award focuses attention on the specific behaviors
      administrators want to encourage to bring the organization's vision and values to
      life. DAISY stories, presented publicly, uplift all who hear them. We can all
      learn a lot from the Barnes family story by remembering the power of compassion,
      the power of gratitude, and the power of recognition.

PMID- 22479965
TI  - Building a clinical ladder for ambulatory care.
AB  - Finding innovative rewards for nursing service will be integral in meeting the
      challenges of future shortages of nursing staff. A clinical ladder is one tool
      worth exploring and perfecting to address those challenges. Exploration of a case
      study demonstrates a method for developing a clinical ladder. Steps and pitfalls
      in developing a clinical path are illustrated. Future uses, benefits, and
      opportunities for clinical ladders are suggested.

PMID- 22479966
TI  - White paper: a nurse's guide to the use of social media.

PMID- 22479967
TI  - Simulation in Kansas practical nursing programs.
AB  - This article discusses the lack of pediatric clinical experiences for practical
      nursing programs in Kansas (specifically in the Kansas City, Kansas Metropolitan
      area). The need for pediatric experience along with how pediatric simulation
      experience can enhance these programs is discussed. A quantitative research study
      evaluating at how implementation of a simulation activity into the practical
      nurse core curriculum impacts knowledge, student confidence, and satisfaction is
      explored.

PMID- 22479968
TI  - Vaccines and immunizations.

PMID- 22479969
TI  - CDC 2011-2012 influenza antiviral medications.

PMID- 22479970
TI  - An (ongoing) shortsighted view on transplant coverage policy.

PMID- 22479971
TI  - A call to action needed to preserve the nephrology specialty.

PMID- 22479972
TI  - RightReturn. Partnering to reduce the high rate of hospital readmission for
      dialysis-dependent patients.
AB  - The rate of rehospitalization is at a critical level. Twenty percent of all
      Medicare patients are rehospitalized within 30 days of discharge, and this rate
      is even higher (36%) for end-stage renal disease patients. Dialysis-dependent
      patients are commonly discharged from the hospital with a decline in various
      health measures (such as hemoglobin, albumin, and estimated dry weight) when
      compared to pre-hospital values, making the common response to resume previous
      orders" in the outpatient setting inadequate. Both quality of care and financial
      penalties by the Centers for Medicare & Medicaid Services have set the stage for
      partnerships between dialysis providers and hospitals to develop strategies to
      reduce readmissions for ESRD patients, and provide for the "RightReturn" to the
      outpatient setting with resumption of their daily lives at home in optimal
      health.

PMID- 22479973
TI  - Key issues in joining an ACO or other clinical integration program.

PMID- 22479974
TI  - Lessons learned: the CMS incentive programs for EHRs.

PMID- 22479975
TI  - Health workforce strategy takes shape.

PMID- 22479976
TI  - The built environment.

PMID- 22479977
TI  - Brown recluse spider bite to the upper lip.
AB  - Brown recluse spiders are predominantly found in south central United States.
      Their bites usually cause mild self-limiting reactions, although localized tissue
      necrosis and rare systemic, potentially fatal, envenomations are known to occur.
      Herein, we report an atypical presentation of a brown recluse bite in a 20 year
      old female who was admitted to the intensive care unit due to angioedema and
      cellulitis. We photographically document the bite site for twenty-four hours
      following envenomation. She received glucocorticoids, antihistamines, antibiotics
      and dapsone while hospitalized and was subsequently discharged with complete
      resolution of symptoms without the development of tissue necrosis or scarring.

PMID- 22479978
TI  - Are physicians a political necessity to advocate for selves, peers and patients?

PMID- 22479979
TI  - Legally speaking: surviving a provider audit.

PMID- 22479980
TI  - Screening for colorectal cancer: the case for quality.

PMID- 22479981
TI  - The Arkansas Autism Developmental Disabilities Monitoring (AR ADDM) project:
      statewide autism surveillance in a rural state.
AB  - In 2002, the Arkansas Autism and Developmental Disabilities Monitoring (AR ADDM)
      project collected data on the number and characteristics of resident children
      aged 8 years using a retrospective record review standardized methodology. This
      paper provides a first-look epidemiology of ASDs among 8 year old Arkansas
      children using data from the 2002 study year. Overall prevalence estimates,
      demographic distribution and a temporal lag from concerns identified to diagnosis
      of ASDs among 8 year olds in Arkansas were similar to that in other sites.
      Dissemination of information that promotes timely resolution of developmental
      concerns and improving educational services will benefit children with autism in
      Arkansas.

PMID- 22479982
TI  - The resolution of pituitary mass in neurosarcoidosis.
AB  - Sarcoidosis is a multisystem disease that primarily affects the sinuses, lungs,
      skin, and eyes. In our case, a young female was referred for evaluation of post
      partum galactorrhea. Initial magnetic resonance imaging revealed a pituitary
      mass. After steroids for mild adrenal insufficiency and sinus disease, the mass
      had resolved on imaging. This led to further investigation and diagnosis of
      sarcoidosis that responded to these steroids. Only 10-15% of patients with
      sarcoidosis have central nervous system involvement.

PMID- 22479983
TI  - Effect of local nifedipine administration on rat gingiva.
AB  - BACKGROUND: Nifedipine, a calcium channel-blocking agent, has been associated
      with gingival enlargement in humans. This enlargement has also been successfully
      established in animal models. Previous investigators have administered nifedipine
      through a systemic route, most commonly by oral intake. The aim of the present
      study was to measure the effects of nifedipine administered directly into rat
      gingival interproximal papillae. METHODS: Twenty-four adult female rats were
      assigned to three groups. Each animal received a series of three injections, one
      week apart; each injection was placed directly into the interdental papilla of
      the maxillary and mandibular central incisors. Group 1 (control) received only
      saline. Group 2 received a low (10 microg/ml) concentration of nifedipine, while
      Group 3 received a higher concentration (500 microg/ml). One week after the last
      series of injections, gingival specimens were harvested from the injection site
      and prepared for histological and immunocytochemical analyses. RESULTS: Specimens
      from Group 3 displayed a significantly greater number of ED2-positive cells
      compared to the other two groups. Specimens from Group 2 showed a significantly
      higher mean count of positive cells compared to Group 1. Collectively, our data
      suggest that repeated local injections of 10 microg/ml and 500 microg/ml
      nifedipine each elicit an inflammatory response in the gingival connective
      tissue. CONCLUSIONS: Immunocytochemical analysis revealed dose-dependent
      increases of resident tissue macrophages in rats receiving nifedipine (p<0.005).
      An increased inflammatory infiltrate also was observed via routine histology.
      Gross macroscopic changes consistent with gingival enlargement were not observed.

PMID- 22479984
TI  - Histological evaluation of osseous defects combined with orthodontic tooth
      movement.
AB  - BACKGROUND: The aim of this study was to histologically evaluate the
      effectiveness of different times of initiating orthodontic tooth movement on
      enhancement of bone formation in surgical bony defects. METHODS: In 18 male
      guinea pigs, 3-4 months of age, a bony defect was created in the alveolar process
      midway between the central incisor and mandibular 1st molar. These bony defects
      were implanted with bioactive glass particles and collagen membrane. According to
      the application of the orthodontic tooth movement, the animals were divided into
      three groups, each comprised of six guinea pigs. In Group I, the orthodontic
      tooth movement was initiated immediately after the surgical procedure. In Group
      II, the orthodontic tooth movement was applied 2 weeks after the surgical
      procedure, while in Group III no orthodontic tooth movement was applied. Section
      blocks for histology were made at 1, 3 and 6 weeks after the surgical procedure.
      RESULTS: All experimental sites showed active bone formation with plump
      osteoblast and osteoid matrix deposition in the treated area. In Groups I and II
      a dense fibrous tissue formation and highly cellular coarse bone were seen at six
      weeks. The histomorphometric analysis showed that Group I revealed the greatest
      number of newly formed trabeculae: 2.4, 6.4 and 8.6 at 1, 3 and 6 weeks,
      respectively. In addition, Group I defects revealed a greater total surface area
      of newly formed bone than Groups I and III: 2.96 mm2 at the end of the study
      period. CONCLUSION: The combined orthodontic/regenerative therapy seemed to
      enhance the process of bone formation. Bone formation was histologically observed
      in all test groups. Defects treated with immediate application of orthodontic
      tooth movement showed a statistically significant increase in trabecular count
      and total surface area of newly formed bone than the other experimental groups.

PMID- 22479986
TI  - 1 a.m. and my tooth hurts.

PMID- 22479985
TI  - Regenerative therapy of osseous defects combined with orthodontic tooth movement.
AB  - BACKGROUND: Combined orthodontic/regenerative therapy can resolve complex
      clinical problems and enhance bone formation. The purpose of this study was to
      evaluate the effectiveness of different times of initiating the active
      orthodontic tooth movement on the regenerative potential of the intrabony
      defects. METHODS: Fifteen adult patients with at least three intrabony defects
      and malocclusion were included. A total of 45 defects were divided into three
      groups and treated in a split mouth design. The defects were treated with
      combined orthodontic regenerative therapy with immediate application of
      orthodontic tooth movement or delayed application of orthodontic tooth movement
      (test groups) or with regenerative therapy alone (control group). The following
      hard and soft tissue measurements were recorded prior to initial surgery and
      after six months and one year: probing depth (DP), clinical attachment level
      (CAL), bone density (BD) and bone fill (BF). RESULTS: The most significant
      results were greater for the group treated with combined orthodontic/regenerative
      therapy with immediate orthodontic tooth movement. The measures for PD reduction
      and clinical attachment level gain were 4 +/- 0.8 and 5.1 +/- 1.4 mm respectively
      for immediate application of orthodontic tooth movement, and 3.7 +/- 0.9 and 4.3
      +/- 0.6 mm with delayed application of orthodontic movement two months later.
      Moreover, immediate orthodontic tooth movement showed the most significant
      increase in bone density and bone fill, which reached 74.2 +/- 14.2 and 3.7 +/-
      1.1 mm respectively at the end of the study period. CONCLUSION: This study
      evaluated the effect of orthodontic tooth movement on enhancement of periodontal
      regenerative outcomes. The results demonstrated that a significant improvement in
      clinical and radiographic parameters was observed. When comparing the different
      groups, a statistically significant difference was found with immediate
      application of orthodontic tooth movement.

PMID- 22479987
TI  - Guarding against concussions. Dr. Andrew Gould protecting athletes with
      innovative mouth guard.

PMID- 22479988
TI  - Are insurance companies dictating care?

PMID- 22479989
TI  - The dental practice app: what is it and why should you have it?

PMID- 22479990
TI  - Maximizing practice profits in tough economic times.

PMID- 22479992
TI  - The interview.

PMID- 22479991
TI  - Patient relations program goes electronic.

PMID- 22479993
TI  - Licorice extract a sweet way to control decay.

PMID- 22479994
TI  - Making a difference to cancer care.

PMID- 22479995
TI  - A new graduate's plea.

PMID- 22479996
TI  - The little hospital that could.

PMID- 22479997
TI  - Nurse experiences poor care.

PMID- 22479998
TI  - Nothing but 'excellent care' from nurses.

PMID- 22479999
TI  - Faith enhances, not defines practice.

PMID- 22480000
TI  - Letter offends nurse's ethical code.

PMID- 22480001
TI  - Judgemental attitudes to addiction.

PMID- 22480002
TI  - One year on....

PMID- 22480003
TI  - 'Sometimes things seem strangely normal'.

PMID- 22480004
TI  - '...We listen to their stories, pray with them and cry with them'.

PMID- 22480005
TI  - A silver lining to earthquake disruption.

PMID- 22480006
TI  - A tough and tiring year.

PMID- 22480007
TI  - Managing lymphoedema in palliative care patients.

PMID- 22480008
TI  - The biology of cancer.

PMID- 22480009
TI  - Support for hospice nurses.

PMID- 22480010
TI  - Adventure therapy proves successful for adolescent survivors of childhood
      cancers.

PMID- 22480011
TI  - Changes to the Crimes Act.

PMID- 22480012
TI  - Fighting for a fairer society.

PMID- 22480013
TI  - Hei nursing shows passion.

PMID- 22480014
TI  - Expanded roles for cancer nurses.

PMID- 22480015
TI  - Patterns of ENT injuries in sports-related accidents.
AB  - To evaluate sports-related ENT injuries regarding demographical trends of
      patients, location and mechanism of injuries, treatments required, and ability to
      return to sports activities, an observational study of patients was conducted.
      Each of the 120 participants in the study was evaluated in a private practice
      clinic. Males were injured more frequently, and the most common ages affected
      were 12 to 15-year-olds. Most injuries were the result of collision with other
      players or from impact of game balls, and most injuries occurred during sporting
      competitions. The most commonly injured structure was the nose. Most patients
      were managed medically and able to return to sporting activities quickly. While
      the most frequent mechanisms for sports injuries are not always preventable,
      health care providers should be aware of these trends described regarding types
      of sports commonly producing injuries and the predominant sites of injury to
      provide optimal care for athletic participants.

PMID- 22480016
TI  - About pit viper snakes and envenomation.

PMID- 22480017
TI  - Chasing zebras.

PMID- 22480018
TI  - My adventure enrolling in the PMP.

PMID- 22480019
TI  - Brave new world.

PMID- 22480020
TI  - The power of vitamins.
AB  - Although a healthy, varied diet should be sufficient for the majority, certain
      population groups are at risk of micronutrient deficiencies, particularly young
      women of childbearing age, whose diets are commonly micronutrient poor and whose
      requirements increase peri-conceptually and throughout pregnancy and lactation.
      Infants and young children are also vulnerable to micronutrient deficiencies,
      associated with the high nutritional demands of rapid growth alongside the
      transition from milk to solids during weaning. The DH and NICE recommend i)
      periconceptual folic acid supplementation ii) vitamin D supplementation during
      pregnancy and lactation, for breastfed infants over 6 months of age (> 1 month if
      at high risk of deficiency), in those taking less than 500ml infant formula and
      for all 1-5 year olds iii) vitamin A supplementation during infancy and early
      childhood. The vitamin and mineral supplement industry is vast, with a third of
      the UK population and half of children being reported to be taking micronutrient
      supplements, although it is predominantly by those who do not need them. Guidance
      on suitable micronutrient supplementation from health professionals, supported by
      dietitians if required, is therefore likely to be welcomed by many families.

PMID- 22480021
TI  - A topic in 10 questions: Gastrointestinal infections from a nutritional
      perspective.

PMID- 22480023
TI  - The phonetics of talk in interaction--introduction to the special issue.
AB  - This overview paper provides an introduction to work on naturally-occurring
      speech data, combining techniques of conversation analysis with techniques and
      methods from phonetics. The paper describes the development of the field,
      highlighting current challenges and progress in interdisciplinary work. It
      considers the role of quantification and its relationship to a qualitative
      methodology. It presents the conversation analytic notion of sequence as a
      version of context, and argues that sequences of talk constrain relevant phonetic
      design, and so provide one account for variability in naturally occurring speech.
      The paper also describes the manipulation of speech and language on many levels
      simultaneously. All of these themes occur and are explored in more detail in the
      papers contained in this special issue.

PMID- 22480022
TI  - The munch bunch: healthy habits start at weaning.

PMID- 22480024
TI  - Beyond the particular: prosody and the coordination of actions.
AB  - The majority of research on prosody in conversation to date has focused on
      exploring the role of individual prosodic features, such as certain types of
      pitch accent, pitch register or voice quality, for the accomplishment of
      specified social actions. From this research the picture emerges that when it
      comes to the implementation of specific actions at specific sequential locations
      conversationalists employ prosodic features systematically, but also with
      considerable variation, and indeed flexibility. This paper suggests a further
      line of enquiry, which pursues a wider, more fundamental role of prosody for
      interaction, and which does not focus on individual prosodic practices or
      features, but on participants' collaborative use of prosody for the
      implementation of one of the most basic interactional decisions: whether to
      continue a previously established action trajectory, or whether to start a new
      one. The data and findings of recent research make it clear that prosody, and in
      fact talk-in-interaction as such, is not appropriately defined by reference to
      individual features, speakers, locations and actions alone, but must be
      approached as a resource and negotiating strategy for social interaction.
      Prosody, therefore, must be described according to its role for both the
      accomplishment, and the coordination of actions across turns and participants.

PMID- 22480025
TI  - Of ens 'n' ands: observations on the phonetic make-up of a coordinator and its
      uses in talk-in-interaction.
AB  - In grammar books, the various functions of and as phrasal coordinator and clausal
      conjunction are treated as standard knowledge. In addition, studies on the uses
      of and in everyday talk-in-interaction have described its discourse
      organizational functions on a more global level. In the phonetic literature, in
      turn, a range of phonetic forms of and have been listed. Yet, so far few studies
      have related the phonetic features of and to its function. This contribution
      surveys a range of phonetic forms of and in a corpus of private American English
      telephone conversations. It shows that the use of forms such as [aend],
      [epsilonn], or [en], among others, is not random but, in essence, correlates with
      the syntactic-pragmatic scope of and and the cognitive closeness of the items the
      and connects. This, in turn, allows the phonetic design of and to contribute to
      the organization of turn-taking. The findings presented are based on conversation
      analytic and interactional-linguistic methodology, which includes quantitative
      analyses.

PMID- 22480026
TI  - Pitch contour matching and interactional alignment across turns: an acoustic
      investigation.
AB  - In order to explore the influence of context on the phonetic design of talk-in
      interaction, we investigated the pitch characteristics of short turns
      (insertions) that are produced by one speaker between turns from another speaker.
      We investigated the hypothesis that the speaker of the insertion designs her turn
      as a pitch match to the prior turn in order to align with the previous speaker's
      agenda, whereas non-matching displays that the speaker of the insertion is non
      aligning, for example to initiate a new action. Data were taken from the AMI
      meeting corpus, focusing on the spontaneous talk of first-language English
      participants. Using sequential analysis, 177 insertions were classified as either
      aligning or non-aligning in accordance with definitions of these terms in the
      Conversation Analysis literature. The degree of similarity between the pitch
      contour of the insertion and that of the prior speaker's turn was measured, using
      a new technique that integrates normalized F0 and intensity information. The
      results showed that aligning insertions were significantly more similar to the
      immediately preceding turn, in terms of pitch contour, than were non-aligning
      insertions. This supports the view that choice of pitch contour is managed
      locally, rather than by reference to an intonational lexicon.

PMID- 22480027
TI  - Negotiating towards a next turn: phonetic resources for 'doing the same'.
AB  - This paper investigates hearers' use of response tokens (back-channels), in
      maintaining and differentiating their actions. Initial observations suggest that
      hearers produce a sequence of phonetically similar responses to disengage from
      the current topic, and dissimilar responses to engage with the current topic.
      This is studied systematically by combining detailed interactional and phonetic
      analysis in a collection of naturally-occurring talk in Norwegian. The
      interactional analysis forms the basis for labeling actions as maintained ('doing
      the same') and differentiated ('NOT doing the same'), which is then used as a
      basis for phonetic analysis. The phonetic analysis shows that certain phonetic
      characteristics, including pitch, loudness, voice quality and articulatory
      characteristics, are associated with 'doing the same', as different from 'NOT
      doing the same'. Interactional analysis gives further evidence of how this
      differentiation is of systematic relevance in the negotiations of a next turn.
      This paper addresses phonetic variation and variability by focusing on the
      relationship between sequence and phonetics in the turn-by-turn development of
      meaning. This has important implications for linguistic/phonetic research, and
      for the study of back-channels.

PMID- 22480028
TI  - Sequential and prosodic design of English and Greek non-valenced news receipts.
AB  - Results arising from a prosodic and interactional study of the organization of
      everyday talk in English suggest that news receipts can be grouped into two
      categories: valenced (e.g., oh good) and non-valenced (e.g., oh really). In-depth
      investigation of both valenced and non-valenced news receipts shows that
      differences in their prosodic design do not seem to affect the sequential
      structure of the news informing sequence. News receipts with falling and rising
      pitch may have the same uptake and are treated in the same way by co
      participants. A preliminary study of a Greek telephone corpus yielded the
      following receipts of news announcements: a malista, a(h) orea, a ne, a, oh.
      These are news markers composed of a standalone particle or a particle followed
      by an adverb or a response token (ne). Analysis of the sequential and prosodic
      design of Greek news announcement sequences is made to determine any
      interactional patterns and/or prosodic constraints. By examining the way in which
      co-participants display their interpretation of these turns I show that the
      phonological systems of contrast are different depending on the sequential
      environment, in much the same way that consonantal systems of contrast are not
      the same syllable initially and finally.

PMID- 22480029
TI  - Combining formal and functional approaches to topic structure.
AB  - Fragmentation between formal and functional approaches to prosodic variation is
      an ongoing problem in linguistic research. In particular, the frameworks of the
      Phonetics of Talk-in-Interaction (PTI) and Empirical Phonology (EP) take very
      different theoretical and methodological approaches to this kind of variation. We
      argue that it is fruitful to adopt the insights of both PTI's qualitative
      analysis and EP's quantitative analysis and combine them into a multiple-methods
      approach. One realm in which it is possible to combine these frameworks is in the
      analysis of discourse topic structure and the prosodic cues relevant to it. By
      combining a quantitative and a qualitative approach to discourse topic structure,
      it is possible to give a better account of the observed variation in prosody, for
      example in the case of fundamental frequency (F0) peak timing, which can be
      explained in terms of pitch accent distribution over different topic structure
      categories. Similarly, local and global patterns in speech rate variation can be
      better explained and motivated by adopting insights from both PTI and EP in the
      study of topic structure. Combining PTI and EP can provide better accounts of
      speech data as well as opening up new avenues of investigation which would not
      have been possible in either approach alone.

PMID- 22480030
TI  - Coordination and interpretation of vocal and visible resources: 'trail-off'
      conjunctions.
AB  - The empirical focus of this paper is a conversational turn-taking phenomenon in
      which conjunctions produced immediately after a point of possible syntactic and
      pragmatic completion are treated by co-participants as points of possible
      completion and transition relevance. The data for this study are audio-video
      recordings of 5 unscripted face-to-face interactions involving native speakers of
      US English, yielding 28 'trail-off' conjunctions. Detailed sequential analysis of
      talk is combined with analysis of visible features (including gaze, posture,
      gesture and involvement with material objects) and technical phonetic analysis. A
      range of phonetic and visible features are shown to regularly co-occur in the
      production of 'trail-off' conjunctions. These features distinguish them from
      other conjunctions followed by the cessation of talk.

PMID- 22480031
TI  - Severe influenza A(H1N1)2009 infection: a single centre experience and review of
      the literature.
AB  - The first influenza pandemic of the 21st century started in April 2009 with an
      outbreak of swine origin influenza A(H1NI)2009 in Mexico and the United States.
      While generally a mild disease affecting mostly school-aged children and young
      adults, most attention went to severe cases of pneumonia in young previously
      healthy individuals or individuals belonging to a risk group. In this article we
      review the literature on the presentation and management of severe cases of
      influenza A(H1N1)2009 in the intensive care unit (ICU), and describe our own
      experience in a tertiary referral centre with ECMO facilities. Pregnant women and
      (bone marrow) transplant patients are two known risk groups for severe influenza
      described more thoroughly in this paper.These severely ill patients are
      characterized by respiratory failure, resulting often in the need of mechanical
      ventilation. As Oseltamivir resistance remains low up till now, early antiviral
      therapy with Oseltamivir is warranted in these cases. Despite pharmacological and
      ventilator management, refractory hypoxaemia is described frequently in these
      patients, with need for rescue therapies like nitric oxide inhalation, high
      frequency ventilation, and extracorporeal membrane oxygenation. The value of the
      use of corticosteroids is under discussion. Despite advances in management
      strategies, mortality and morbidity in these severe cases remains high. In the
      first influenza season after the pandemic, winter 2010/2011, influenza
      A(H1N1)2009 is the major influenza A strain in Europe, resulting in reports with
      increased mortality and morbidity compared to pre-pandemic seasonal influenza.
      "Continuing vigilance for severe influenza in patients not belonging to the
      classical influenza risk group might still be warranted for the upcoming
      influenza season".

PMID- 22480032
TI  - Infections with verotoxin-producing escherichia coli O157:H7 and other serotypes,
      including the outbreak strain O104:H4.
AB  - Through the acquisition of mobile genetic elements, the normally harmless
      commensal Escherichia coli evolved into a highly adapted human pathogen.
      Pathogenic strains of E. coli are associated with urinary tract infections,
      sepsis/meningitis, and diarrhoea. At least six different diarrhoeagenic E. coli
      pathotypes have emerged during the past three decades as human pathogens of
      public health importance worldwide. In this review, we focus on the clinical
      features, pathogenic mechanisms, and diagnostic strategies of verotoxin-producing
      E. coli (VTEC) that are associated with sporadic cases and epidemics of
      gastrointestinal disease throughout the world. Recently, an E. coli strain of
      serotype O104:H4 combining verotoxin production with virulence factors of another
      pathotype, the enteroaggregative E. coli (EAEC), emerged as the cause of a severe
      outbreak in Europe.

PMID- 22480033
TI  - Selecting an appropriate and reimbursed anti-osteoporotic treatment option: a
      practical tool in the Belgian setting.
AB  - Osteoporosis is a highly prevalent and often undertreated disease in the elderly.
      Osteoporosis-related fractures are associated with significant morbidity and
      mortality. Anti-osteoporotic drugs are only reimbursed by the Belgian government
      if strict conditions are fulfilled. The aim of this paper was to create a
      practical tool to guide the physician and other health care professionals to make
      an appropriate choice. Two flowcharts, based on Belgian reimbursement criteria
      and literature review were developed. Both tools provide an overview of the
      reimbursed pharmacological agents in the management of osteoporosis in male and
      female subjects.

PMID- 22480034
TI  - Subjective sleep quality and daytime sleepiness in a large sample of patients
      with chronic fatigue syndrome (CFS).
AB  - Chronic fatigue syndrome (CFS) is characterised by incapacitating fatigue in
      combination with a number of minor criteria, including unrefreshing sleep without
      further specifications, in the absence of psychiatric and internal disease. As
      little data exist on subjective sleep quality and daytime sleepiness, these
      parameters were assessed in a large sample of CFS patients. Consecutive patients
      with a diagnosis of CFS in a tertiary referral centre filled out the Fatigue
      Questionnaire (FQ), Medical Outcomes Study 36-Item Short Form Health Survey (MOS
      SF-36), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI).
      Inclusion comprised 415 individuals (mean age 40.5 yr, SD 7.9, range 18-64; 86%
      female). Mean FQ (26.90; SD 4.04), mean Global Physical Health from the MOS SF-36
      (29.30; SD 12.25) and Global Mental Health from the MOS SF-36 (49.62; SD 18.31)
      scores corresponded with literature data for similar CFS samples. High mean ESS
      (10.51; SD 5.52) and global PSQI (10.17; SD 4.02) were observed. No significant
      relationship was found between ESS and global PSQI. In contrast, regression
      analysis demonstrated a significant cubic relation between ESS and 'PSQI without
      daytime dysfunction'. A subgroup (n=69) with an insomnia-like phenotype low ESS
      (<5), high PSQI (mean 11.51; SD 3.86) was observed. The assessment of subjective
      sleep quality and daytime sleepiness in a large sample of CFS patients indicated
      high mean PSQI and ESS values. ESS and 'PSQI without daytime dysfunction' were
      inversely related at the spectral ends of ESS. A distinct subgroup with clinical
      features of insomnia was identified.

PMID- 22480035
TI  - Psychological, social and school implications of asthma: a comparison of Belgian
      French-speaking children having asthma with healthy children.
AB  - The present study aimed to explore the psychosocial implications of asthma among
      Belgian French-speaking children. Ninety-nine parents of children having asthma
      (Mage=11.40, SD=2.35) and 102 parents of children without asthma (Mage=11.25,
      SD=.81) participated in the study. Parents filled in the Child Behaviour
      Checklist and a demographic questionnaire. Results showed that children having
      asthma were assessed by their parents as having more internalizing, social and
      attention problems and as having less competence in doing activities (e.g.,
      sports, hobbies, jobs) than their healthy peers. Significant differences also
      appeared between genders for attention problems, anxiety/depression, activities,
      social and school competences, indicating that boys were more vulnerable to
      psychological and social difficulties than girls but they had better school
      competences than girls. Finally, results showed no difference for psychological,
      social, and school adjustment between children who controlled and partly
      controlled their asthma. These findings emphasize the importance of screening
      children who would be at risk for having psychosocial problems and developing
      multidisciplinary interventions for children with asthma and for their families.

PMID- 22480036
TI  - Cyclic Cushing's syndrome.
AB  - Because glucocorticoids are necessary to sustain life and maintain homeostasis,
      adrenal disorders, if not detected in a timely fashion, can have serious
      consequences. Cyclic Cushing's syndrome is a disease characterized by rhythmic
      fluctuations in glucocorticoid production. In patients with this disorder, both
      clinical and biochemical spontaneous remissions may occur and therefore the
      activity of the hypothalamic-pituitary-adrenal axis between the cycles may be
      undisturbed. The clinical manifestation of cyclic Cushing's syndrome may be
      complex and varied, differing not only between patients but also in the same
      patient on a daily to monthly basis. The presence of cyclic Cushing's syndrome
      should always be considered in patients with a clinical presentation of
      hypercortisolism coexisting with normal glucocorticoid plasma levels and a
      paradoxical response to the dexamethasone test. We here present a detailed case
      report on a patient diagnosed with cyclic Cushing's syndrome. We report
      diagnostic and treatment strategies used in our patient and their impact on the
      course and outcome of the disease.

PMID- 22480037
TI  - A hypogranular variant of acute promyelocytic leukaemia showing a heterogenic
      immunophenotype with CD34, CD2, HLA-DR positivity: a case report and review of
      the literature.
AB  - We report the case of a 46-year-old man who presented with the hypogranular
      variant of an acute promyelocytic leukaemia (APL). RT-PCR analysis for detection
      of the t(15;17) fusion transcript confirmed the cytological findings by
      demonstrating a bcr-3 type PML/RARalpha rearrangement. According to the WHO
      classification, this leukaemia fulfilled the criteria for 'Acute promyelocytic
      leukaemia with t(15;17)(q22;q12)'(1). Immunophenotyping revealed a leukaemic
      population with an aberrant expression of markers. Besides the presence of the
      expected immunophenotypic markers in APL (CD45 with low density, CD13+, CD33+,
      CD15-, CD117+ and MPO+), the population showed a positivity for CD34, CD2 and HLA
      DR for at least a part of the malignant promyelocytes. Since the expression of
      these three markers, all together, is rather unique, we reviewed the literature
      to prove the relationship of this specific immunophenotype with morphology,
      clinical and molecular findings.

PMID- 22480038
TI  - Pre-terminal renal insufficiency in a patient with enteric hyperoxaluria: effect
      of medical management on renal function.
AB  - Enteric hyperoxaluria causes tubular deposition calcium oxalate crystals and
      severe chronic interstitial nephritis. We describe a patient with pre-terminal
      renal failure due to oxalate nephropathy after ileal resection. Increased oral
      hydration, low oxalate diet, and oral calcium carbonate and potassium citrate
      supplements resulted in a significant improvement of renal function. During the
      three-year follow-up, urinary oxalate concentration was repeatedly reduced below
      the crystallization threshold and serum creatinine decreased from 4.5 to 1.7
      mg/dL. This case illustrates the benefit of combining and optimizing dietary and
      medical management in enteric hyperoxaluria, even in patients with advanced
      chronic kidney disease.

PMID- 22480039
TI  - Capnocytophaga species and perinatal infections: case report and review of the
      literature.
AB  - Capnocytophaga species are part of the normal human oral bacterial flora.They are
      recognized as opportunistic pathogens leading to various extra-oral infections
      including septicemia, osteomyelitis, abscesses and keratitis and they have been
      rarely reported as a cause of chorioamionitis and neonatal infection. We here
      report the first two cases of chorioamionitis produced by Capnocytophaga
      sputigena and the recently described C. leadbetteri in Belgium. Both isolates
      were correctly identified at the genus level, in the first 24 hours of incubation
      by MALDI-TOF.

PMID- 22480040
TI  - Invasive pulmonary aspergillosis due to a multi-azole resistant Aspergillus
      fumigatus.
AB  - A patient with invasive pulmonary aspergillosis due to an azole-resistant
      Aspergillus fumigatus is described. Despite treatment change from voriconazole to
      amphotericin B as soon as the resistance data were available, the patient died.
      Azole resistance is an emerging problem, which significantly complicates the
      management of A. fumigatus infections. It should be considered in every patient
      with an invasive A. fumigatus infection who is not responding to voriconazole
      therapy.

PMID- 22480041
TI  - Clostridium perfringens hip arthritis in a haemodialysis patient.
AB  - Haemodialysis patients have acquired immunity disturbances, co-morbidities and a
      vascular access, factors predisposing them to infection and bacteraemia.
      Clostridium perfringens is an anaerobic bacterium potentially causing severe
      infections, including rarely septic arthritis. We report the first case of
      Clostridium perfringens septic arthritis in a haemodialysis patient and suggest a
      haematogenous spread. After rapid joint lavage combined with appropriate anti
      microbial therapy, the patient recovered.

PMID- 22480042
TI  - Infective endocarditis-related bilateral spontaneous pneumothorax in a
      haemodialysis patient.

PMID- 22480043
TI  - Marshall's vein persistence: a rare and occasional finding during pacemaker
      implantation.
AB  - In adults the oblique vein of Marshall is usually absent or very thin, and it is
      hard to be found. In this case report we describe a case of persistence observed
      during pacemaker implantation.

PMID- 22480044
TI  - Multiple endocrine neoplasia 2A and pregnancy: a medical and ethical challenge.

PMID- 22480045
TI  - False positive Borrelia serology and facial paralysis due to anaplastic lymphoma
      mimicking lyme.

PMID- 22480046
TI  - Let's talk about pain.

PMID- 22480047
TI  - Strategic planning: is it really necessary?

PMID- 22480048
TI  - The pain experience of patients on maintenance hemodialysis.
AB  - This article describes the pain experience of patients on maintenance
      hemodialysis. Nephrology nurses have noted that patients on maintenance
      hemodialysis experience pain; however, it may not be adequately assessed or
      treated. A qualitative approach was utilized. Data were analyzed using content
      analysis. Twenty-five patients on outpatient hemodialysis were interviewed during
      their scheduled hemodialysis treatments. Patient pain experiences were related to
      physical pain, such as joint pain, as well as discomfort from being immobile.
      There were also descriptions of emotional and social pain. Patients utilized
      analgesics and other approaches, such as exercise, for pain. Patients also
      described pain management within the context of a dialysis unit. Patients'pain
      experiences require additional assessment and intervention. Further research is
      warranted to identify strategies to facilitate comfort.

PMID- 22480049
TI  - Experiences of kidney failure: a qualitative meta-synthesis.
AB  - The purpose of this study was to conduct a qualitative meta-synthesis on the
      experiences of kidney failure in the nursing literature. Database searches were
      not limited by date; however, only 13 peer-reviewed articles, theses, and
      dissertations met inclusion criteria. Meta-synthesis of the texts suggests
      individuals with kidney failure have experiences of paradoxical nature, including
      occurrences of restricted freedom that bring about distant connection, dependent
      autonomy, abnormal normalcy, and uncertain hope. When nurses are attuned to the
      seemingly contradictory nature of experiences of individuals living with kidney
      failure, they may be better able to develop strategies that will increase quality
      of life for these patients.

PMID- 22480050
TI  - Hypertension management in patients receiving hemodialysis: the benefits of home
      blood pressure monitoring.
AB  - Patients with end stage renal disease on hemodialysis are at risk for
      cardiovascular events and increased mortality. Hypertension contributes to these
      risks and can be difficult to assess due to unreliable blood pressure (BP)
      measurements at dialysis centers. A clinical practice grant from the American
      Nephrology Nurses'Association allowed for the purchase of 35 home BP monitors to
      study the use of these monitors to provide additional information for BP
      management. Findings indicated that home BP monitoring can be an effective tool
      in hypertension management.

PMID- 22480052
TI  - Evaluation of an educational program: a report from the hemodialysis unit in
      Zagaxig University hospitals, Egypt.
AB  - The knowledge and performance of hemodialysis nursing staff at Zagazig University
      Hospitals, Egypt, were evaluated using a quasi-experimental design. Participants
      received an educational program developed from international standards and
      national guidelines. The number of nurses who achieved satisfactory knowledge and
      performance scores increased significantly post-intervention, and were sustained
      for three months after the intervention. A strong, positive correlation was also
      found between the participants' knowledge and their performance.

PMID- 22480051
TI  - Racial/ethnic differences in illness, perceptions in minority patients undergoing
      maintenance hemodialysis.
AB  - This study examined whether racial/ethnic differences in illness perceptions
      exist among patients on maintenance hemodialysis. One hundred sixty-one patients
      with end stage renal disease (ESRD) undergoing maintenance hemodialysis (20%
      African Americans, 44% Hispanics, 9% Filipinos, and 27% Koreans) completed the
      Revised Illness Perception Questionnaire. Korean participants had higher
      emotional disturbance than their counterparts, whereas African-American
      participants had higher negative perceptions of personal intervention or medical
      treatment controlling their disease. This study indicates that patients from
      different racial/ethnic backgrounds undergoing maintenance hemodialysis may
      perceive their disease differently. This phenomenon could affect clinical
      outcomes and may require different therapeutic approaches.

PMID- 22480053
TI  - Anemia management: one protocol does not fit all.

PMID- 22480054
TI  - Managing communications and behavioral challenges in dementia.

PMID- 22480055
TI  - Good health, one determinant at a time.

PMID- 22480056
TI  - Expanding the care team to improve drug adherence.

PMID- 22480057
TI  - Nursing your community garden.

PMID- 22480058
TI  - Pathways to housing: a response to homelessness in Calgary.

PMID- 22480059
TI  - Advocacy inside the maze.

PMID- 22480060
TI  - Focusing your care: working with clients with vision loss.

PMID- 22480061
TI  - Mindful matters.

PMID- 22480062
TI  - Taking control of your financial future.

PMID- 22480063
TI  - Cancer and sex: out in the open.

PMID- 22480064
TI  - Relationships are the antidote to toxic stress.

PMID- 22480065
TI  - Psychiatric and neuropsychological manifestations of systemic lupus
      erythematosus.
AB  - BACKGROUND AND AIM: Systemic lupus erythematosus (SLE) is a chronic autoimmune
      disease which may involve any organ and system, including peripheral, autonomic,
      and central nervous system (CNS). According to the American College of
      Rheumatology nomenclature, the term "neuropsychiatric SLE" identifies
      neurological and psychiatric syndromes occurring in patients at any time, not
      attributable to other causes, and categorized in three main groups, namely
      neurological syndromes of CNS, neurological syndromes of peripheral nervous
      system, and diffuse psychiatric/neuropsychological syndromes. The SLE
      neurological and psychiatric manifestations are usually reported together, and
      specific data on SLE psychopathology are limited. We aimed to electively focus on
      prevalence, pathogenesis, diagnostic aspects, and current therapeutic options of
      diffuse psychiatric/neuropsychological SLE syndromes in adult and pediatric
      patients. METHODS: A detailed search of concerning literature was performed in
      PubMed (U.S. National Library of Medicine) database. RESULTS: In both adulthood
      and childhood, psychiatric/neuropsychological syndromes are frequent and
      challenging SLE manifestations, whose prevalence is likely underestimated, owing
      to systematic assessment is not routinely performed in patients. Ischemia (due to
      disease-related vascular injury or cerebral vasospasm) and
      inflammatory/immunopathologic mechanisms appear to be the main pathogenic
      factors. Standardized treatment guidelines are not presently available, however,
      therapeutic recommendations have been proposed. CONCLUSIONS: Due to the high
      prevalence and significant suicidality risk of SLE psychiatric syndromes,
      systematic assessment to provide prompt diagnosis and adequate care should be
      critical part of SLE patients' evaluation protocol, and universally accepted and
      validated evaluating tools should be performed and introduced in the clinical
      practice, as well as widely experienced therapeutic strategies.
      (www.actabiomedica.it)

PMID- 22480066
TI  - "Immune activation, aging and gender" and progression of liver disease.
AB  - Hepatitis C is the predominant cause of liver disease in the HIV-positive
      population and the most important of the non-AIDS-related causes of death. HCV
      disease tends to become chronic more frequently in HIV-positive subjects, and to
      evolve more rapidly into cirrhosis of the liver. The rapidity of the evolution
      varies considerably from one individual to the next and, if in HIV-negative
      subjects cirrhosis manifests itself after approx. 40-50 years of disease, in HIV
      positive subjects it emerges 10-15 years earlier (1, 2). The severity of the
      fibrosis is not a gradual event and can be worsened by many factors. Age, sex,
      duration of the infection and assumption of alcohol are the most well-known
      variables; obesity, diabetes, steatosis and metabolic disorders are equally
      important factors that affect the progression of liver disease (3). The severity
      of the liver disease is very different in men compared to women. Being male is
      undoubtedly one of the factors most closely related to the gravity of fibrosis
      (4). In HCV mono-infected women, cirrhosis appears from the age of 60 onwards.
      With the onset of the menopause, in fact, the progression of liver disease
      accelerates and the risk of developing cirrhosis or cancer of the liver becomes
      particularly significant in women over 50. The conditions of menopause or of
      amenorrhea, irrespective of age, are therefore correlated with the progression of
      liver disease (5). This evidence led researchers to theorize on the possible anti
      fibrogenic role of estrogens. In fact, estrogens in physiological doses in the
      plasma of women in fertile age contribute to controlling the progression of liver
      disease through antioxidant mechanisms and lipid peroxidation control mechanisms
      (6). The reduction of estrogens during the menopause is closely linked to the
      increase of metabolic disorders. During the menopause, steatosis and
      cardiovascular diseases increase in parallel with the increase of atherogenic
      lipoproteins, the accumulation ofintra-abdominal fat and the onset of insulin
      resistance (3, 7). Recent works have demonstrated how the concentration of HCV
      viremia in plasma correlates with the degree of insulin resistance and with the
      concentration of circulating triglycerides, demonstrating how the role of HCV in
      altering the hepatic lipid and glucide metabolism is functional to its
      replicative capacity. The correlation between the HCV viral load and the
      metabolic set-up is still unclear in the mono-infection and has been rarely
      studied in the HIV/HCV co-infection, where the picture is further altered by the
      metabolic impact of certain antiretroviral therapies. Over recent years, most of
      the HIV/HCV co-infected population, belonging - as is common knowledge - to the
      old intravenous drug user risk categories, have reached the age of 50 and have 20
      25 years' history of liver disease. The women are reaching the menopause and are
      frequently characterized by prolonged states of amenorrhea. This conditions
      exposes HIV-positive women and the co-infected population, currently in care in
      our centres, to a sudden and rapid worsening of the liver condition. Over the
      last few years, we are also witnessing the launching on the market of new anti
      HCV molecules which must, of necessity, find an outlet as new drug applications
      for HIV/HCV co-infected patients, as well as being used to the best advantage in
      populations with particular complications. (www.actabiomedica.it)

PMID- 22480067
TI  - Physical activity and sedentary lifestyle in children with type 1 diabetes: a
      multicentre Italian study.
AB  - BACKGROUND: Regular Physical Activity (RPA) is one of the cornerstones of Type 1
      Diabetes (T1D) therapy, but conflicting results are reported in the literature.
      AIM: To compare (RPA) and Sedentary Lifestyle (SL) among children with type 1
      diabetes (T1D) and healthy peers. SUBJECTS AND METHODS: Seven Italian paediatric
      diabetes centres enrolled 129 children with T1D and 214 healthy peers who were
      interviewed by a telephone questionnaire on physical activity level, sedentary
      lifestyle and clinical data. RESULTS: Compared to healthy peers, children with
      T1D: performed the same amount of RPA, were more frequently engaged in team
      sports (p = 0.018), described RPA as an enjoyable activity (p = 0.033), not
      boring (p = 0.035), a chance to spend time with peers (p = 0.033) and to meet new
      friends (p = 0.016). Children with T1D were finally used to consume less snacks
      during watching TV (p < 0.001) or after physical activity (p < 0.001 ). HbA1c
      values were not related with time spent in physical activity, in watching TV or
      in playing video-games. CONCLUSIONS: Most interviewed children with T1D are
      physically active and perform the same amount of exercise as their healthy peers.
      They demonstrate to consider RPA a source of enjoyment and sociality and not a
      therapeutic imposition. (www.actabiomedica.it)

PMID- 22480068
TI  - Differences between ethnic minority and native children in breakfast habits.
AB  - Aim of this study was to investigate the breakfast habits in a cohort of school
      ethnic minority (EM) children admitted to a summer sport school (SSS) in order to
      evaluate the possible differences with their Italian peers (IP). One hundred
      seventy-nine children aged 6-14 years were interviewed through a questionnaire
      about breakfast behaviors and nutrition habits. The results were compared with
      those obtained in a randomized sample of 179 Italian peers (IP) attending the
      same SSS. EM children skip breakfast more frequently than IP (15% vs 7%; p =
      0.029). The omissions are attributed to the lack of time (45% vs 54%) and not
      being hungry upon waking (44% vs 38%). During weekends the percentage of
      breakfast skippers decreased of about 3 percentage points but persisted a
      significant difference between the two groups (p = 0.024). EM children who did
      not have breakfast show a mean BMI higher than breakfast consumers (p = 0.05).
      Bakery products and milk were the most frequently consumed food and drink in EM
      and IP children (68% vs 70% and 71% vs 76% respectively). EM children chose and
      prepared personally breakfast at home more frequently than IP (54% vs 22%). These
      EM children were more inclined to skip breakfast (p = 0.025) and to have an
      elevated BMI (p = 0.006) than IP. An educational program, for ethnic minority
      families, in different languages and according to their cultural, religious and
      socio-economic influences could be a possible means for changing their lifestyle
      and reducing their risk to become overweight.

PMID- 22480069
TI  - Endoscopic treatment of vesicoureteric reflux in paediatric patient: results of a
      long-term study.
AB  - BACKGROUND AND AIM OF THE WORK: Vesicoureteric reflux is the most common uropathy
      in paediatric age. It may be treated with open surgery, antibiotic therapy or
      endoscopic injection. The purpose of this work is to determine outcomes and
      experiences of parents with children who underwent endoscopic treatment for VUR.
      MATERIALS AND METHODS: In a period of 5 years (from 2004 to 2009) 48 patients (20
      boys and 28 girls, mean age 5,5, range 1-17) underwent endoscopic treatment for
      VUR. Sample included 31 cases of primary reflux (64,6%), 11 complex cases of VUR
      (6 duplex system, 3 duplex system with ureterocoele, 2 bladder exstrophy) and 6
      children (12,5%) with VUR secondary to neurogenic bladder. All procedures were
      performed by the same surgeon. A questionnaire assessing experiences with
      endoscopic treatment was administered to all families. RESULTS: Follow-up lasted
      from a minimum of 6 months to 5 years. Overall cure rate was 68,7% (33/48) per
      child after a single injection, a second injection performed in cases with VUR
      recurrence raised it to 81,2% (39/48 patients). Overall cure rate per grade of
      VUR was 60% (3/5) for grade I, 94,1% (16/17) for grade II, 86,9% (20/23) for
      grade III, 64,7% (11/17) for grade IV and 85,7% (6/7) for grade V. Minimal
      postoperative complications were recorded: 2,1% urinary tract obstruction, 12,5%
      macro-haematuria, 6,2% lumbar pain, 4,1% urinary retention or strangury. The
      results of the survey given to families were encouraging. CONCLUSIONS: Endoscopic
      treatment for VUR seems to be a feasible procedure as primary intervention.

PMID- 22480070
TI  - Changes of spleen dendritic cells in the terminal stage of multiple organ
      dysfunction syndrome.
AB  - Immune dysfunction is associated with the onset of multiple organ dysfunction
      syndrome (MODS). To study the immune damage in the spleen, we observed
      pathological features of the spleen and investigated the number of splenic
      dendritic cells and T lymphocytes in MODS patients, 9 human MODS cases and 25
      normal spleens were examined by light microscope, electron microscope and
      immunohistochemistry (S-100, CD11c, CD205, CD1a, CD80 and HLA-DR). There was
      resolution and dispersion of splenic corpuscles, especially white corpuscles,
      accompanied by apoptosis of a large amount of lymphocytes and increased number of
      splenic dendritic cells (DCs). CD1a+/S-100+ DCs and CD205 /S-100 DCs increased
      but the CD80+/CD11c+ DCs and CD1a+/HLA-DR DCs decreased in MODS patients(p <
      0.01), CD80+/CD11c+ DCs and CD1a/HLA-DR-DCs were mainly surrounding the remote
      periarterial lymphoid sheath and in red pulp. The ratio of CD4+/CD8+ T lymphocyte
      declined markedly. The results indicated that at the terminal stage of MODS, the
      spleen was seriously damaged, the splenic DCs were inactivated and many
      lymphocytes were lost, especially CD4+ T, which induced T cells incapacitation
      and immune suppression. It is suggested that there is an important relation
      between changes of splenic dendritic cells and loss of lymphocyts and
      pathogenesis of MODS.

PMID- 22480071
TI  - The use of collatamp in total hip arthroplasty.
AB  - Total Hip Arthroplasty (THA) is one of the most common orthopedic operations in
      the world. The number of THA is expected to grow and with it the number of
      associated complications. Although improved surgical technique and the
      development of more scrupulous asepsis has decreased the incidence of
      periprosthetic joint infection (PJI), it remains one of the most feared
      complications of joint arthroplasty. The purpose of this study is to present the
      use of antibiotic-loaded collagen sponges (Collatamp EG) in the prophylaxis and
      treatment of PJI. For this scope a case report is described. The advantages
      offered by the antibiotic loaded sponges in terms of high and sustained
      concentration of antibiotic at the site of infection, diffused by the fully
      reabsorbable carrier, showed to be a an important adjuvant therapy in the
      treatment of PJI. Low systemic concentration of the drug and a wide versatility
      in surgical application are other advantages of this dispositive.

PMID- 22480072
TI  - Efficacy of liraglutide in a patient with type 2 diabetes and cryptogenic
      cirrhosis.
AB  - In this work Author presents a case report of a female patient of 65 years old
      who had suffered from type 2 diabetes mellitus and from concomitant cryptogenic
      cirrhosis. She was treated with liraglutide, an analogue of human GLP-1,
      obtaining an optimal metabolic control associated with an improved clinical
      condition for the cirrhosis.

PMID- 22480073
TI  - Carcinoma in situ (CIS) of the testis.
AB  - Abstract. Testicular cancer is the most common malignancy in 20- to 34-years-old
      males. It has been stated that testicular cancer derives from a precocious
      lesion, the carcinoma in situ of the testis, also known as Intratubular Germ Cell
      Neoplasia (IGCN) or Testicular Intraepithelial Neoplasia (TIN). This lesion
      deserves great attention, because the diagnosis of CIS may lead to a precocious
      diagnosis of testicular cancer. Generally, the diagnosis of CIS is incidental.
      Every physician should know the management of this precocious lesion, as the
      correct management of CIS can lead to a decrease of the incidence of overt
      testicular cancer (the most frequent malignancy in young men). Moreover, the
      correct diagnosis and management of CIS can shorten the hospital stay, reduce the
      cost, and improve the social impact of the testicular cancer.

PMID- 22480074
TI  - The Future of Nursing report: staff nurses step up!

PMID- 22480075
TI  - Influence your practice.

PMID- 22480076
TI  - Scrubs of excellence.

PMID- 22480077
TI  - Offering whole person care: dealing with fear.

PMID- 22480079
TI  - Christian ethics--HOT? (or not?).

PMID- 22480078
TI  - Nursing school: a balancing act.

PMID- 22480080
TI  - Help patients defy diverticular disease.
AB  - Diverticular disease is a chronic disorder that can significantly impact quality
      of life, and incidence of this disease is increasing. This article outlines the
      history, incidence, pathophysiology, signs and symptoms, diagnosis, treatment,
      and nursing management of patients with diverticular disease. Tools to assist
      with patient education and resources for spiritual care, inner healing needs, and
      support with healthy lifestyle choices are provided.

PMID- 22480081
TI  - Catholic orders' influence on nursing: 1900-1920.
AB  - Doing God's work through vocation and caring for the less fortunate has been a
      long-time focus of the Catholic faith. In the early 20th century Catholic orders
      of nuns made major contributions to nursing education and clinical practice. This
      historical research article illustrates the sisters' vast influence on nursing as
      they introduced spirituality into quality patient care.

PMID- 22480082
TI  - Short-term missions: not what I expected.
AB  - This article relays the experiences of a nurse practitioner serving in Haiti,
      before and after the 2010 Earthquake. She concludes, "I realized that God had
      indeed called me to serve--not as I had envisioned, but as he needed."

PMID- 22480083
TI  - Nursing perspective on the Genesis account of creation.
AB  - Biblical accounts of creation tell the origin of the world and the beginning of
      God's relationship with humankind. Azusa Pacific University assigns graduate
      nursing students a faith integration project analyzing Creation accounts through
      the eyes of a nurse researcher. This report integrates eight students'
      investigations of Genesis 1 and 2, offering deep, rich insight into nursing
      practice.

PMID- 22480084
TI  - Stress at work? Build resilience, renew your mind, be transformed.
AB  - Workplace stress, including bullying and horizontal violence, is a common problem
      in nursing. Christians have unique resources to build resilience, renew the mind,
      and be transformed in dealing with these problems.

PMID- 22480085
TI  - Public access to defibrillation (PAD): implementing a church program.
AB  - For every minute without cardiopulmonary resuscitation and defibrillation, the
      odds of surviving cardiac arrest decrease by 7% to 10%. Churches can implement a
      public access to defibrillation (PAD) program and help save lives. This article
      outlines steps and resources for setting up a PAD program.

PMID- 22480086
TI  - "Am I going to die, aunt Deborah?".
AB  - A nurse relays her experience with the death of her 10-year-old nephew, and
      offers resources for helping children and families facing death.

PMID- 22480087
TI  - What role does power play in spiritual care?

PMID- 22480088
TI  - The legacy of ordinary nurses.

PMID- 22480089
TI  - The rest of the lesson.

PMID- 22480090
TI  - The still, quiet voice.

PMID- 22480091
TI  - The "good" cancer: WDTC.

PMID- 22480092
TI  - Migraine and vascular events--how often and how far?

PMID- 22480093
TI  - A comparative study of oral tramadol and ibuprofen in postoperative pain in
      operations of lower abdomen.
AB  - The objective of this study was to assess efficacy and safety of oral tramadol in
      postoperative pain in operations of lower abdomen as compared to oral ibuprofen.
      Eighty patients undergoing operations in the lower abdomen under spinal
      anaesthesia were randomly assigned to two parallel groups--ibuprofen 400 mg
      thrice daily and tramadol 100 mg thrice daily, both orally after food. Treatment
      was given single-blind for 5 days in the postoperative period. Patient's
      perception of pain scored byvisual analogue scale (VAS) and wound tenderness
      assessed by a 3-point ordinal scale were the primary efficacy parameters. A
      steady decline in VAS pain score from baseline to study end (99.7 +/- 2.75 to
      54.4 +/- 9.71 in the ibuprofen group and 97.3 +/- 3.14 to 52.5 +/- 9.95 in
      tramadol group) indicated good analgesic efficacy in both groups. Within groups,
      comparisons showed highly significant difference in VAS score between baseline
      and each of the subsequent assessment time points (p < 0.001). Between groups
      differences were not significant at any point. There were no intergroup
      differences in wound tenderness at baseline or at study end. Rescue medication
      was needed by 6 subjects on ibuprofen but none on tramadol (p = 0.011). Both
      regimens were well tolerated. It can be thus concluded that oral tramadol is
      safe, effective and comparable to ibuprofen as analgesic for relieving pain in
      the postoperative period in patients undergoing operations in the lower abdomen.
      The need for rescue medication for breakthrough pain may be less with tramadol.

PMID- 22480094
TI  - A study on cardiovascular risk factors among care-providers of an apex hospital
      of Kolkata.
AB  - Cardiovascular diseases, mostly a lifestyle related disease is going to be an
      epidemic in near future. Eighty per cent deaths due to cardiovascular diseases
      occur in low and middle-income group of people. A cross-sectional observational
      study was undertaken among 208 care-providers of different departments of the
      Institute of Postgraduate Medical Education and Research, Kolkata to assess the
      prevalence of general, physical activity related and dietary risk factors. The
      study subjects were classified into medical (doctors), auxiliary (nurses,
      technical staffs) and supportive (peons, sweepers) categories according to their
      job responsibilities. With the help of risk factor scoring system developed by
      the investigators the prevalence of different category of risk factors were
      compared among different categories of care-providers in association with some
      related biological characteristics. The general risk factors found significantly
      increased (p < 0.001) with increase in age. The physical activity related risk
      scores were more in females than males. But the difference was not statistically
      significant. The supportive staffs had significantly higher general risk factors
      than doctors and auxiliary staffs. Regarding physical activity related risk
      factors it was significantly lower in supportive staffs than the other two
      categories. The picture was different in case of dietary risk factors that were
      found to be significantly lowest among auxiliary staffs.

PMID- 22480096
TI  - Childhood migraine.

PMID- 22480095
TI  - Trigeminal neuralgia.

PMID- 22480097
TI  - Headache in rheumatological disorders.

PMID- 22480098
TI  - Headache--as a prelude to sudden death.

PMID- 22480099
TI  - Once a week (200 mg) elemental iron: an effective option for prophylaxis in non
      anaemic pregnant women.
AB  - To evaluate effectiveness of 200 mg elemental iron once per week for prophylaxis
      in non-anaemic pregnant women, a prospective longitudinal study with
      observational design was carried out at a tertiary care teaching hospital. Fifty
      pregnant women received daily (group 1) and 50 pregnant women received weekly
      (group II) oral therapy (100 mg elemental iron, 1.5 mg folic acid and 15 microg
      of vitamin B12). Haemoglobin, PCV estimation were carried out during follow-up
      periods at 4, 8 and 14 weeks. Iron profile (serum iron, TIBC, serum ferritin)
      estimation was done before and after 14 weeks of iron supplementation.
      Haemoglobin, PCV and serum iron increased significantly in both the groups (p <
      0.001) but on intergroup comparison it was significantly higher in group I than
      group II (p < 0.001). Serum ferritin improved in both the groups but improvement
      was not significant in weekly supplemented group. Compliance was better and side
      effects were less in group II as compared to group I (11.36% versus 39.9%) The
      supplementation of pregnant women once per week with 200 mg of elemental iron is
      an effective option for prophylaxis in mild anaemic or non-anaemic pregnant
      women.

PMID- 22480100
TI  - Role of histopathology in vitiligo.
AB  - Vitiligo is in most cases diagnosed clinically, so obvious are the features of a
      well developed lesion of this disease. Other investigations are rarely required.
      However, occasionally vitiligo especially in its early evolving stage or in some
      of its localised expressions may pose diagnostic difficulties as the lesions are
      hypopigmented rather than depigmented and other differential diagnoses may be
      considered. The histopathological changes in vitiligo in sections stained with
      haematoxylin and eosin (H&E) are often very subtle and may be inconclusive.
      Special staining procedures like the Fontana-Masson staining may help in reaching
      a definite diagnosis. The DOPA reaction which demonstrates viable and functional
      melanocytes may also be used but is technically difficult to perform.

PMID- 22480101
TI  - Study of serum lipase, alpha-amylase and pancreatic amylose in gall-stone
      diseases.
AB  - Silent gall-stone causes significant morbidity and mortality and its incidence in
      India as well as in whole world is on the rise. It has positive correlation with
      development of carcinoma gall bladder. So far no predictive study has been done
      to show its correlation with biochemical markers. The present study has been
      aimed to establish whether simple enzymatic markers can predict association with
      cholelithiasis. Study group has been selected from the patients attending general
      surgery OPD of a tertiary healthcare centre with complaints of vague abdominal
      pain, flatulence and dyspepsia. A total of 61 cases (male = 18, female = 43) were
      studied and data matched with age and sex matched control. The biochemical
      markers studied are serum alkaline phosphatase, serum lipase, serum alpha-amylase
      and serum pancreatic amylase. Patients with obstructive cholelithiasis, duct
      stones, pancreatic insufficiency and malignancy are excluded from the study. The
      results were analysed by Student's t-test. Alkaline phosphatase in all the above
      mentioned cases was not significantly different from the control group (40
      female, 21 male healthy individuals). A significant association was found out
      with serum alpha-amylase (p < 0.05) and a highly significant association was
      found out with pancreatic amylase (p < 0.001). Results of serum lipase however
      were inconclusive (p = 0.1). Pancreatic amylase can be estimated at a reasonable
      cost and costwise may prove to be a marker of gall-stone diseases which are in
      many cases silent preventing further complications and chances of Malignancy
      especially where alkaline phosphatase isinconclusive.

PMID- 22480102
TI  - Effects of ribavirin on measles.
AB  - To assess the beneficial effectof ribavirin on measles, a study was conducted
      among one group (group A) of measles patients who were randomly assigned and
      treated with ribavirin along with supportive management and anothergroup who were
      also randomly assigned and treated by supportive therapy only acted as controls
      (group B) between January 2006 and December 2009 at ID&BG Hospital, Kolkata. Both
      the groups included 50 patients each and all were confirmed by serum IgM antibody
      detection. The duration of fever along with constitutional symptoms like malaise,
      cough, coryza, conjunctivitis, lacrimation, rash, hospital staying and
      complications of both the groups were compared. The duration and severity of
      fever and constitutional symptoms like anorexia, malaise, conjunctivitis, cough,
      etc, and maculopapularrash were much less in group A than those of group B and
      there were no complications in group A whereas there were many complications in
      group B cases and the duration of hospital stay of patients in group B were much
      more than those of group A cases. These results suggest that the beneficial
      effect of ribavirin on measles is established and each and every measles patient
      should be treated by ribavirin along with standard symptomatic managemen
      irrespective of duration regarding illness.

PMID- 22480103
TI  - Red blood cell mechanics.
AB  - During the 120-day life span, the erythrocyte undergoes excessive passive
      deformation. Cell shape, cytoplasmic viscosity and membrane deformability and
      stability are key features in red cell deformability. These three cellular
      components are described in a nutshell in this review article.

PMID- 22480104
TI  - Guillain-Barre syndrome occurring during dengue fever.
AB  - Various types of neurological manifestations are described in dengue fever, of
      which peripheral neuropathy is rarely reported. We are reporting such a case that
      presented with three days' history of fever and weakness of all the four limbs of
      two days' duration. On investigations it turned out to be acute motor sensory
      axonal neuropathy (AMSAN) type of Guillain-Barre syndrome with decrease platelet
      counts and positive serology for dengue. All other causes of acute polyneuropathy
      were ruled out by history and relevant investigations. Patient improved with
      intravenous immunoglobulin and other supportive therapy.

PMID- 22480105
TI  - Solitary fibrous tumour of the orbit: an unusual presentation.
AB  - Solitary fibrous tumour is a rare tumour that usually arises from the pleura and
      very uncommonly from the orbit. This unusual unilateral orbital mass can be
      differentiated from the more common haemangiopericytoma by the use of
      histopathological and immunohistochemical studies. The tumour is strongly
      Immunoreactive for CD34, which supports its diagnosis.

PMID- 22480106
TI  - Laurence Moon Bardet Biedl syndrome associated with dyslipoproteinaemia.
AB  - Laurance Moon Bardet Biedl (LMBB) syndrome is a rare disorder characterised by
      retinitis pigmentosa, hexadactyly, obesity, mental retardation and hypogonadism.
      In the present case report the patient presented with the features of Laurence
      Moon Bardet Biedl syndrome in association with dyslipoproteinaemia.

PMID- 22480107
TI  - Primary ovarian lymphoma in a child.
AB  - Ovarian tumour is rarely seen in paediatric age group and primary ovarian non
      Hodgkin's lymphoma is very uncommon. A child presenting with acute abdomen was
      detected to have bilateral solid ovarian tumours. Because of torsion of the right
      ovarian tumour and complete replacement of the ovarian tissue by the tumour on
      left side, bilateral salpingo-oophorectomy was done. Bilateral primary ovarian
      lymphoma was diagnosed on histopathological examination. Immunohistochemistry was
      suggestive of B-cell lineage. She had eight cycles of chemotherapy and at 28
      months follow-up doing well without any sign of any recurrence or any evidence of
      metastasis.

PMID- 22480108
TI  - Hydatid cyst of orbit.
AB  - A 40-year-old woman presented with protrusion and diminution of vision of left
      eye for 3 months. CT scan of orbit revealed an intra-orbital cystic space
      occupying lesion. Exenteration of the left orbit was done and histopathological
      examination of the cystic mass proved it to be a case of hydatid cyst.

PMID- 22480109
TI  - [Mechanism of injury--trauma kinetics. What happend? How?].
AB  - INTRODUCTION: Understanding the mechanism of injuries represents a key element in
      blunt and penetrating trauma management. METHOD: Systematic review of the main
      types of the modem trauma mechanisms, using Medline, Cochrane Library and Embase
      databases. RESULTS: To properly understand the road car accident injuries, trauma
      surgeon should know as many details from the scene: the speed of cars, impact
      direction, if the car rolled over, if occupants were restrained, if airbags
      exploded, vehicle telemetry, extrication time. Motorcyclists are 20 to 30 times
      more at risk for severe injuries or death than the four-wheel vehicle occupants.
      Current evidence shows a significant decrease in injuries severity by increasing
      use of seat-belts, motorcycle helmets, childrestrains and speed limit. Despite
      this, few countries around the world have road safety laws relating to key
      factors that can be considered sufficiently comprehensive in scope. Many modern
      trauma systems use for prehospital triage mechanism of injury criteria.
      CONCLUSIONS: The trauma surgeon should know the mechanism of injury. This allows
      a high suspicion for potential injuries, their early diagnosis and increased
      quality in the care of trauma patients.

PMID- 22480110
TI  - Albendazole associated to surgery or minimally invasive procedures for hydatid
      disease--how much and how long.
AB  - Cystic echinococcosis is parasitic disease due to the larval stage of the
      metacestode Echinococcus granulosus in the liver (80%), lungs, kidneys, spleen,
      myocardium etc. Humans are accidental intermediate hosts. Diagnosis is based on
      laboratory and imaging studies. Treatment is multimodal, surgical and medical.
      Risks for dangerous complications and relapses are quite common. Adequate follow
      up is needed. Albendazole has a central role in the medical therapy of the
      disease.

PMID- 22480111
TI  - Fractal-like kinetics, a possible link between preconditioning and sepsis
      immunodepression. On the chemical basis of innate immunity.
AB  - In a recent paper the authors hypothesized that the so called fractal-like enzyme
      kinetics of intracellular reactions may explain the preconditioning effect in
      biology (Vasilescu C, Olteanu M, Flondor P, Revue Roumaine de Chimie. 2011;
      56(7): 751-7). Inside cells the reaction kinetics is very well described by
      fractal-like kinetics. In the present work some clinical implications of this
      model are analyzed. Endotoxin tolerance is a particular case of preconditioning
      and shows similarities with the immunodepression seen in some sepsis patients.
      This idea offers a theoretical support for modulation of the enzymatic activity
      of the cell by changing the fractal dimension of the cytoskeleton.

PMID- 22480112
TI  - [Risk factors for anastomotic leakage following colorectal resection for cancer].
AB  - PURPOSE: To identify the risk and prognosis factors and their predictive value
      for anastomotic leakage after colorectal resections following cancer. PATIENTS
      AND METHODS: 1743 consecutive patients who underwent colic resections or rectal
      resections for colo-rectal cancer between 1996-2005 in Surgical Clinic no. 3
      (Cluj-Napoca, Romania) were retrospectively analysed. RESULTS: A total of 54
      (3.09 percent) anastomotic leaks were confirmed. Univariate analisys showed that
      the preoperative variables significantly associated with anastomotic leakage
      included weight loss, smoking, cardiovascular disease, lung disease,
      hypoproteinemia, diabetes, anemia, leukocitosis, presence of two or more
      underlying diseases. Use of alcohol, cerebrovascular disease, bowel preparation,
      mode of antibiotic prophylaxis, type of handsewn anastomosis, tumor location,
      tumor stage and tumor histology were nonsignificant variables. Hipoproteniemia (S
      - proteins < 60g/dl) and anemia (S Hb < 11) remained significant in logistic
      regression model. CONCLUSIONS: Our study shows that a value of S-proteins lower
      than 60 g/l and s-Hb lower than 99 g/l can be consider as predictive marker for
      anastomotik leak deshiscence.

PMID- 22480113
TI  - Pharyngoesophageal junction neoplasia--therapeutic management.
AB  - Not only the anatomy but the treatment and the prognosis of these tumors are
      intermediate between hypopharyngeal and esophageal tumors. After a portion of the
      esophagus is removed or complete esophagectomy, a conduit must be established.
      The authors reviewed the experience of Prof. Cristian Popescu in total pharyngo
      laryngectomy and his technique of pharyngoesophageal reconstruction with
      synthetic esophageal prosthesis. We have some 21 patients who underwent an
      esophageal reconstruction with Montgomery esophageal tube. This is a very
      important new, modem, interdisciplinary approach bewteen the head and neck
      surgeon and the general/thoracic surgeon to treat the pharyngo-laryngo-esofageal
      neoplasia with one stage reconstruction. The follow up for these patients shows
      that this reconstruction method is a good, reliable choice with low costs and
      considerable advantages for the quality of life. Surgery for these patients
      should be considered primarily palliative and the optimal reconstruction should
      preserve the quality of life for the duration of survival.

PMID- 22480114
TI  - Nodular thyroid cancer. Diagnostic value of real time elastography.
AB  - BACKGROUND: The most important aspect in the diagnostic approach of thyroid
      nodule is identifying the malignancy Elastography is a newly technique that
      measures the elasticity of tissue, after applying a external force, standardized
      control. US elastography is currently used in differentiation of malignant from
      benign lesions. PATIENTS: This prospective study included 69 patients, mean age
      50.08 +/- 12.43 years, 67 females and 2 men, with thyroid nodules on conventional
      US, with a volume higher than 0.20 ml. All patients underwent surgery after
      complete evaluation. Extemporaneous and postsurgical histopathological exam was
      performed in all cases. Tissue stiffness was scored from one (greatest
      elasticity) to 5 (no strain), according to the UENO scale. RESULTS: In the 69
      cases we diagnosed 107 nodules, which we analyzed. 27 nodules had score 1 on US
      elastography and 37 nodules had score 2. All nodules were benign on
      histopathological exam. Score 3 was found in 33 cases, 32 benign and one
      papillary carcinoma. Score 4 as found in 10 cases, all carcinomas. ES score of 4
      is highly predictive for malignancy (sensitivity of 90.9%, specificity of 98.96%,
      positive predictive value of 100%, negative predictive value if 98.60%). The
      diagnostic quality of elastography was independent of the nodule volume.
      CONCLUSION: US elastography has a good potential in diagnosing thyroid
      malignancy, independent of nodule volume, allowing the study of small nodules,
      less than 0.5 ml.

PMID- 22480115
TI  - Predictors for duration of hospital stay after abdominal wall hernia repairs.
AB  - BACKGROUND: To identify variables those predict length of hospital stay
      separately after groin, primary ventral and incisional hernias. METHODS: A total
      of 1170 groin, primary ventral, and incisional hernia repairs (n = 959, 132, 79
      respectively) and their perioperative variables were analyzed. For each subgroup
      of hernia type, univariate analysis was performed. Multivariate logistic
      regression model was used to determine independent variables that predict length
      of hospital stay in each group of hernia. RESULTS: Out of 1170 repairs; 959 were
      inguinal, 132 were primary ventral repairs and 79 were incisional hernia repairs.
      Strangulation (p = 0.021), ASA III-IV class (p < 0.001), longer duration of
      surgery (p < 0.001), systemic postoperative complications (p < 0.001), and local
      postoperative complications (p < 0.001) were associated with longer length of
      hospital stay in inguinal hernia repairs; type of repair procedure (p = 0.028),
      longer duration of surgery (p < 0.001), and systemic postoperative complications
      (p = 0.006) were associated with longer length of hospital stay in ventral
      primary hernias repairs; ASA III-IV class (p = 0.027) and longer duration of
      surgery (p = 0.003) were associated with longer length of hospital stay in
      incisional hernia repairs. CONCLUSIONS: Postoperative hospital stay can be
      predicted before the operation by evaluating certain factors related to the
      patient or procedure. Longer duration of surgery predict longer hospital stay in
      all types of ventral hernias where as strangulation, high ASA class, systemic
      local postoperative complications, and type of repair procedures may predict
      longer length of hospital stay in different ventral hernia types.

PMID- 22480116
TI  - Gastrojejunocolic fistula: report of six cases and review of the literature.
AB  - Six gastrojejunocolic fistulae were recorded at our service between 1995-2005.
      All the fistulae occurred in men who had gastric resection performed for duodenal
      ulcer. METHOD: Diarrhea, weight loss, postprandial pain and fecal breath were the
      clinical findings present in descending frequency. Preoperative diagnosis was
      possible in 5 patients by endoscopy and barium contrast studies. In five patients
      the option was a one-stage procedure with revision gastrectomy and segmental
      resection of the transverse colon. In one case simple dismantling of the fistula
      was performed. RESULTS: Although in two patients anastomotic leakage developed no
      mortality was recorded.

PMID- 22480117
TI  - Postherapeutic follow-up of colorectal cancer patients treated with curative
      intent.
AB  - BACKGROUND AND AIM: Based on published data showing that despite a curative
      intent treatment approximately 50% of colorectal cancer (CRC) patients will
      present with disease relapse, and on the results of meta-analysis which showed
      improved survival by using intense posttreatment follow-up programs, we aimed in
      the present study to evaluate the additional benefit of routine abdominal
      ultrasound in the follow-up program of CRC patients. MATERIAL AND METHOD: We
      conducted a prospective study, on 107 patients diagnosed with stage III CRC.
      Patients follow-up included: history and physical examination, CEA determination,
      and abdomino-pelvic US every 3 months. RESULTS: Recurrent disease was observed in
      36% of cases after a median follow-up interval of 24 months. The liver was the
      most frequent isolated site of disease recurrence (62%). Serum CEA level
      increased in most patients (69%) with recurrent disease. Also, a high percentage
      of relapses was diagnosed by routine abdominal US (62%). CONCLUSIONS: Our study
      illustrates the benefit of intense follow-up (CEA, abdominal US) after curative
      treatment of CRC.

PMID- 22480118
TI  - [Perioperative immunologic changes in colorectal cancer patients].
AB  - The aim of the study was to investigate the perioperative immunological profile
      in colon cancer patients and possible correlations with disease. To investigate
      the changes in immune mediators profile induced by tumor resection, we assessed
      the serum levels of cytokines (IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha),
      chemokines (MIP-1alpha, MCP-1, ENA-78) and growth factors (VEGF, bFGF) in colon
      cancer patients before, during and after surgery and compared the results with
      those measured for a group of healthy controls. We have used XMap profiling
      technology (Luminex) that allows simultaneous measurement of multiple parameters
      in small volumes of samples. Circulating levels of proinflammatory cytokines IL
      1, IL-6, IL-8 and antiinflamatory cytokine IL-10 were elevated in cancer patients
      with respect to healthy controls. Before surgery, serum levels of MCP-1 and MIP
      1alpha positively correlated with the levels of proinflammatory cytokines. During
      surgery, an increase in serum concentration of all determined mediators was
      noticed, with positive correlation between TNF-alpha, IL-8, MCP-1 and MIP-1alpha.
      Interestingly, these correlations were no more noticed one week after operation.
      Postoperatively, cytokines levels decreased as compared to those noticed before
      surgery, but still higher than in control group. These preliminary results
      suggest that both tumor and surgical act may influence immune mediators' network.

PMID- 22480119
TI  - Peculiarities of diagnosis and treatment in the polyp-cancer sequence.
AB  - Colorectal cancer, a public health problem with major social implications, has
      attracted major economic resources and specialized centers focused in the
      direction of obtaining an early diagnosis from effective screening means in the
      last decades. It is obvious that the therapeutic results and the social costs are
      primarily dependent on the precocity of diagnosis. The present paper aims to
      bring to attention a number of orientations, which may open a new perspective in
      approaching the genetic and molecular level of these lesions. Out of these, the
      value of the molecular screening based on the detection of the APC gene located
      on the short arm of chromosome 5, a method that allows the selection of the
      subjects to be subjected to further endoscopic screening is underlined. The
      optimization of the costs as well as the increased compliance of the subjects to
      such a method is thus accomplished.

PMID- 22480120
TI  - [Role of procalcitonin in monitoring the antibiotic therapy in septic surgical
      patients].
AB  - BACKGROUND: Based on the need for rigorous monitoring of antibiotic and a proper
      assessment of patients with sepsis, procalcitonina as biological marker appears
      to have significant value, being proposed for both detection and for evaluation
      of bacterial infection and antibiotic management. MATERIAL AND METHODS: We
      conducted a prospective study on a group of 73 patients admitted in Surgical
      Clinic II you SCJU Constanta between 2010-2011, which is included in the study
      criteria ACCP/SCCM Consensus Conference in 1992. We have made determinations of
      the PCT, in dynamic, since the admission of patients, with imunocromatographic
      method, monitoring the antibiotics on the studied group depending on cut-off
      fluctuations and PCT. RESULTS: The level of procalcitonin reflect the degree of
      systemic inflammatory response. PCT dosages were performed in 17 patients without
      inflammation/infection in 21 patients with local infections, 20 with systemic
      infection (sepsis), 7 with severe sepsis and septic shock 3/MSOF. In the studied
      group we excluded 5 patients with associated pathology (on the first day after a
      major trauma, major surgery, burns, treatment with drugs that stimulate the
      release of pro-inflammatory cytokines, small cell lung cancer, medullary thyroid
      carcinoma) in that the PCT was in the absence of an inflammatory process
      cresct/infectious manifesto. Starting, monitoring and stopping the antibiotic was
      carried out based on PCT levels. The dosage of procalcitonin (PCT) revealed
      significantly elevated values in patients with severe sepsis and septic
      shock/MSOF. PCT was significantly lower in patients with sepsis compared with
      those with septic shock, and the difference between PCT values in patients with
      sepsis and severe sepsis was the limit of statistical significance. PCT values
      were not predictive of death, however. CONCLUSIONS: In conclusion, dynamic
      measurement of PCT may be a predictor for life-threatening infections with
      antibiotics that can monitor and direct the time and efficiency. The value of PCT
      as a guide of antibacterial therapy which can reduce mortality and morbidity in
      surgical septic patients remains to be fully evaluated by future studies, but we
      can say that the determination of this biomarker could be introduced in the
      dynamically protocol of tracking the clinical course of septic patients.

PMID- 22480121
TI  - Free tissue transfer in hand surgery--essential step in hand transplantation.
AB  - INTRODUCTION: The development of microsurgery allowed huge advancements in the
      reconstructive surgery of the upper limb. The use of free digital transfer
      started a true revolution for the reconstruction of the mutilated, functionally
      compromised hand, with multiple amputations. Slowly, surgeons started using free
      tissue transfers in other reconstructive procedures of the hand, forearm and arm.
      This way they avoided amputating a limb and they realized quality reconstructions
      in a single surgical step in cases in which classical methods did not apply. We
      shouldn't neglect to mention that free tissue transfers, along with hand
      replantation, represent an important step for microsurgery centers in preparing
      the hand transplant. MATERIAL AND METHODS: There have been 48 cases of free
      tissue transfers of the upper limb in the Plastic Surgery Department of the
      "Bagdasar-Arseni" Emergency Hospital between 2000 and 2010, of which 18 free
      digital transfers, 11 free tissue transfers of the hand, 15 transfers of the
      forearm and 4 of the arm. RESULTS AND DISCUSSION: Of the total 48 cases we
      studied, 4 have been total failures and 6 cases presented partial necrosis of the
      transferred tissue, all of which have been managed with ulterior corrective
      procedures. We used free tissue transfer in cases where there was no other
      surgical option and also in cases where other methods applied, but free tissue
      transfer provided a superior quality solution.

PMID- 22480122
TI  - [Innovative technique in large benign prostatic hyperplasia--enucleation by
      plasma vaporization].
AB  - OBJECTIVES: The trial evaluated a new endoscopic treatment alternative for large
      benign prostatic hyperplasia (BPH) cases, the bipolar plasma enucleation of the
      prostate (BPEP), in terms of surgical efficiency, safety and short-term
      postoperative results. MATERIALS AND METHODS: A total of 30 patients with
      prostates larger than 80 ml were included in the study. All cases were
      investigated preoperatively and at 1 and 3 months after surgery by international
      prostate symptoms score (IPSS), quality of life score (QoL), maximum flow rate
      (Q(max)) and abdominal and transrectal ultrasonography. RESULTS: All procedures
      were successfully performed. The enucleation and morcellation times were 69.8
      minutes and 18.5 minutes, while the morcellated tissue weight was 77 grams. The
      mean hemoglobin drop was 0.8 g/dl and the mean catheterization period and
      hospital stay were 26.5 hours and 2.3 days. The rate of early irritative symptoms
      was 10%. At 1 and 3 months, significant improvements were determined concerning
      the IPSS (5.3 and 4.8), QoL (1.2 and 1.1) and Q(max) (25.9 and 25.1 ml/s).
      CONCLUSIONS: BPEP represents a promising endoscopic approach in large BPH cases,
      characterized by good surgical efficacy, reduced morbidity, fast postoperative
      recovery and satisfactory follow-up parameters.

PMID- 22480123
TI  - [Surgical treatment of inguinal hernia with peritoneal laparoscopy].

PMID- 22480124
TI  - Port-site metastasis after laparoscopic surgery for colorectal cancer--still a
      real concern? Case report and review of the literature.
AB  - BACKGROUND: The recently published long-term oncological results of the large
      multicentric randomized prospective trials, such as COST, COLOR, and UK MRC
      CLASICC, have diminished once more the initial skepticism from the mid '90s,
      regarding the safety of laparoscopic approach for colorectal cancer surgery. The
      actual incidence of port-site metastases (PMSs) in the laparoscopic surgery for
      colorectal cancer is just arround 1%, being statistically simmilar to the wound
      metastases after open colorectal surgery. We followed up a series of 122
      laparoscopic-assisted resections for colorectal adenocarcinoma, 49 for rectal
      cancer and 73 for colon cancer. The operations were performed at the Center of
      Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute,
      Bucharest, Romania, between 1st January 2002 and 31st december 2008. There was
      only one case of PMS (0.81%). CASE-REPORT: A 83-year old man developed a
      recurrent parietal tumor on the site of extraction minilaparotomy, 4 months after
      laparoscopic-assisted right hemicolectomy for a Dukes C, poorly differentiated
      (G3) adenocarcinoma of the cecum. DISCUSSIONS: We have reviewed the scientific
      relevant literature regarding the incidence and multi-factor etiology of PMSs in
      the laparoscopic surgery for colorectal cancer as well as the methods suggested
      for prevention of parietal tumour dissemination to the trocar or wound sites.
      CONCLUSION: PMSs consecutive to laparoscopic surgery for colorectal cancer are no
      longer a big concern enough to contraindicate this beneficial surgery for
      oncological reasons. However, PMSs continue to represent a reality which must be
      taken into consideration by any laparoscopic surgeon. There are different
      prevention measures that should be applied for reducing the occurence of this
      possible complication.

PMID- 22480125
TI  - An unusual sarcomatous retroperitoneal metastasis. A rare case report with a
      brief literature review.
AB  - Retroperitoneal sarcomas are rare tumors associated with a high rate of
      recurrence and very bad prognosis. Their only efficient treatment is a negative-
      margin surgical resection that is extremely difficult to achieve. Retroperitoneal
      metastases from extremity sarcomas are considered unusual. In literature, such a
      metastatic pattern is described extremely rarely. In this paper we report a case
      of a very aggressive extremity chondrosarcoma, associated with local recurrence,
      multiple distant metastases, that finally led to a retroperitoneal metastasis.
      The recurrence and progression of the sarcoma in this localization were
      impressive, with a fast overcome of therapeutic options. Chemo- and radiotherapy
      have not proved to be efficacious in this context and they could have had a role
      in the deterioration of patient state of health. New tumor markers for the
      detection and follow-up of these tumors should be considered.

PMID- 22480126
TI  - [Hydatid cyst of anterior mediastinum].
AB  - INTRODUCTION: Echinococcosis is endemic in Romania. Hydatid cyst can develop in
      any segment or organ, but the most frequent locations are liver and lung.
      Mediastinal hydatid lesions are extremly rare and only a few cases exists in the
      medical literature. MATERIAL AND METHOD: Between 1994 and 2011 Thoracic Surgery
      Clinic, UMF "Carol Davila" there were 3 patients diagnosed and surgical trated
      for hydatid cyst of mediastinum. The patients were 2 men and 1 woman aged of 20,
      37 and 52 years. All hydatid cysts were located in the anterior mediastinum and
      all were solitary lesions when diagnosed. RESULTS: In 1 case the positive
      diagnosis was made preoperatively, in the other 2 the diagnosis was
      intraoperative. The approach was through thoracotomy. One cyst was complicated
      (nonviable thymic hydatid cyst), treated by ideal cystectomy, and 2 cysts were
      viable. There was 1 postoperative complication: gaseous cerebral embolism
      remitted after medical treatment, caused by the intraoperative use of H2O2 as
      scolicide agent. CONCLUSIONS: Although very rare, anterior mediastinal hydatid
      cysts must be considered in every patient with anterior mediastinal mass.
      Complete surgical excision is the treatment of choice; surgery followed by
      parasiticide therapy provides complete cure.

PMID- 22480127
TI  - Pyoderma gangrenosum--a postoperative "pseudo-infection".
AB  - Pyoderma gangrenosum is a skin ulcerative necrosis, due to dermal neutrophilic
      infiltration, through a non-infectious exacerbation of cell -mediated immunity.
      Being characterized by pathergy, the disease may be triggered by surgery; in this
      case, it is easily mistaken for a postoperative infection. We report a case of
      pyoderma gangrenosum after coronary artery bypass surgery. The patient developed,
      from the 7th postoperative day, around the incisions, dermo-epidermic lesions
      specific for the disease, high fever with chills and a severe biological
      inflammatory syndrome. Treatment for wound sepsis was ineffective. After pyoderma
      gangrenosum was recognized, corticosteroids (Prednisone 80 mg/d) led, in two days
      time, to a spectacular improvement, and in 7 weeks, to complete epithelization of
      the lesions. If after debridement of a supposedly infected wound (with pustules,
      bullae or ulcerations), there is no improvement, but a centrifugal extension of
      the lesions, with a "sepsis-like" syndrome and persistent negative cultures, one
      should think at pyoderma gangrenosum; in that case, not the antibiotics, but
      corticosteroids (or other immunosuppressants) are the treatment.

PMID- 22480128
TI  - Bilateral hip dislocation in a 79 years patient.
AB  - Bilateral simultaneous dislocation of the hip is an unusual occurrence,
      especially if there is no previous history of hip abnormality or ligamentous
      laxity. Most of the reports published until now most frequently describe this
      type of injury in adults. The majority of case reports present patients with ages
      ranging between 20 and 30 years old, because at this age the bone is strong
      enough not to suffer a fracture but a dislocation. The oldest patient with
      bilateral simultaneous dislocation of the hip described in literature (to our
      knowledge) is 65 years old. We present the case of a 79 year old man that was
      involved in an agricultural accident in which a heavy load fell on both his feet
      while he was laying on the ground. Anteroposterior pelvic radiograph reveal
      bilateral posterior hip dislocation with an associated left-side acetabular
      fracture and also a minimum displaced anterior left pelvic ring fracture. Both
      hips were reduced within three hours of presentation by closed manipulation under
      spinal anaesthesia. Literature search revealed no case presentation that reported
      a bilateral simultaneous dislocation of the hip in elderly--to our knowledge,
      this is the first.

PMID- 22480129
TI  - [Hydatid cysts with hepatic and pelvic synchronous location--clinical case].
AB  - About 75% of all hydatid cysts are located in the liver and they are singular.
      Extrahepatic hydatid cysts are rare pre- and intra-operative findings. The
      majority of such locations are consecutive from a hepatic primary. We present the
      clinical case of a 28-years woman, clinically diagnosed with a pelvic tumor.
      Ultrasonography and CT-scan showed two large tumors: a 17/10 cm left liver cyst,
      that contained free floating hyperechogenic hydatid sand and a 12/11 cm pelvic
      cyst, that displaced the urinary bladder, the uterus, the sigmoid colon and the
      rectum. The diagnosis of synchronous hepatic and pelvic hydatid cysts was
      suggested. Explorative laparotomy revealed a large cystic tumor of the left
      liver, 20/15 cm, with many daughter cysts. The cysts were aspirated through a
      closed suction system and flushed with hypertonic saline, then its cavity was
      unroofed and drained. We also found a voluminous hydatid cyst of the pelvis,
      which was treated in the same manner. After 2 days, a bile duct communication was
      diagnosed, with a medium biliary output--300-400 ml/day. The fistulography
      confirmed the connection with the biliary ducts. An endoscopic sphincterotomy was
      then performed, followed by a favourable evolution. According to the scientific
      criterias from the literature, we discussed the treatment and the outcome of
      these extrahepatic locations.

PMID- 22480130
TI  - Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus
      proportional doses.
AB  - OBJECTIVES: The aim of this study was to compare the efficacy and safety of doses
      of fentanyl buccal tablet (FBT) proportional to doses of opioids used for
      background analgesia versus dose titration starting with the minimal dose for the
      management of breakthrough cancer pain (BTcP). METHODS: A total of 82 cancer
      patients with BTcP who were receiving strong opioids in doses of at least 60 mg
      of oral morphine equivalents and having acceptable background analgesia, were
      selected for a multicenter unblinded study. Forty-one patients were randomized to
      receive FBT in doses proportional to the daily opioid doses for four consecutive
      episodes of BTcP (group P). Forty-one patients underwent dose titration of FBT,
      with an initial dose of 100 ug, for four consecutive episodes (group T). Pain
      intensity and symptoms associated with opioid therapy were measured before
      administering any dose of FBT (T0) and 15 minutes after (T15). RESULTS: In all,
      80 patients were considered for analysis (39 and 41 patients in group P and T,
      respectively). Patients were receiving a mean of 126 +/- 100 mg of oral morphine
      equivalents (range 60-480 mg) for background analgesia. A total of 293 episodes
      of BTcP (144 and 149 in group P and T, respectively) were treated and considered
      for analysis. No differences were found in the decrease of pain intensity between
      the two groups. However, in patients receiving doses of oral morphine equivalents
      of >120 mg/day, a significant number of patients obtained a decrease in pain
      intensity >50% in group P in comparison with group T (p = 0.040). Also, the need
      for rescue medication was significantly more frequently reported in group T for
      the first episode of BTcP (p < 0.0005). No differences in the level of adverse
      effects were observed between the two groups. No differences in patients'
      satisfaction were reported. CONCLUSION: According to the data obtained in this
      study, there is no evidence for the use of dose titration in the management of
      BTcP in opioid-tolerant patients. Indeed, doses proportional to basal opioid
      regimen for background pain seem to be effective and safe in the majority of
      patients. Further studies should confirm this data in patients receiving higher
      doses of opioids, with other rapid-onset opioids, and in other settings.

PMID- 22480131
TI  - Efficacy and safety of fentanyl sublingual spray for the treatment of
      breakthrough cancer pain: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND AND OBJECTIVES: A number of transmucosal fentanyl formulations have
      been developed for the management of breakthrough cancer pain (BTCP). Sublingual
      delivery of fentanyl, formulated as fentanyl sublingual spray, offers the
      potential for more rapid and greater absorption of fentanyl and associated onset
      of analgesic effect compared with other formulations. The objective of this study
      was to assess the efficacy and safety of fentanyl sublingual spray for the
      treatment of BTCP. RESEARCH DESIGN AND METHODS: This was a randomized, double
      blind, placebo-controlled phase III trial conducted in opioid-tolerant patients
      with BTCP. An open-label titration period was followed by a double-blind
      treatment period during which patients received fentanyl sublingual spray (100
      1600 mcg) or placebo. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00538850. MAIN OUTCOME MEASURES: The primary efficacy measure was summed pain
      intensity difference at 30 minutes (SPID(30)). Secondary efficacy measures
      included total pain relief at 30 minutes (TOTPAR(30)) and patient global
      evaluation of study medication at 30 minutes. Efficacy measures were also
      assessed at various time points from 5-60 minutes postdose. Adverse events were
      monitored throughout the study. RESULTS: A total of 130 patients were treated
      during the titration period, of whom 98 (75.4%) entered the double-blind period.
      Relative to placebo, fentanyl sublingual spray significantly improved mean SPID
      scores from 5 minutes (p = 0.0219) through 60 minutes (p < 0.0001), including the
      primary endpoint at 30 minutes (p < 0.0001). Fentanyl sublingual spray produced
      significantly greater pain relief (expressed in terms of TOTPAR) from 5 through
      60 minutes (p < 0.0001), and significantly greater global evaluation of treatment
      effectiveness (p < 0.0001), compared with placebo. During double-blind treatment,
      the most frequently reported adverse events were nausea (7.1%), hyperhidrosis
      (5.1%), and peripheral edema (5.1%). Serious adverse events occurred in seven
      patients (5.4%) during titration and six (6.1%) during double-blind treatment;
      none were considered related to treatment. CONCLUSIONS: These findings indicate
      that treatment with fentanyl sublingual spray results in effective relief of
      BTCP, with a rapid onset of action, and is well tolerated.

PMID- 22480132
TI  - Lewis acid promoted highly diastereoselective Petasis Borono-Mannich reaction:
      efficient synthesis of optically active beta,gamma-unsaturated alpha-amino acids.
AB  - An efficient and straightforward method for the preparation of highly
      enantiomerically enriched beta,gamma-unsaturated alpha-amino acid derivatives by
      a Lewis acid promoted diastereoselective Petasis reaction of vinylboronic acid, N
      tert-butanesulfinamide, and glyoxylic acid has been developed. The synthetic
      utilities of the approach were demonstrated by the rapid and convenient
      construction of challenging cyclopenta[c]proline derivatives.

PMID- 22480133
TI  - Cross-linked DNA: propargylated ribonucleosides as "click" ligation sites for
      bifunctional azides.
AB  - 2'-O or 3'-O-propargylated adenosines and ribothymidines were used as click
      targets for cross-linking of oligonucleotides with aliphatic and aromatic azides.
      The cross-link generates a sugar modification at the 2'-O-ligation site.
      Inexpensive ribonucleosides were used as starting materials. Cross-linking of
      oligonucleotides was performed at internal or terminal positions. Hybridization
      of homodimers with two complementary single strands resulted in stable ligated
      DNA duplexes.

PMID- 22480134
TI  - Dissolution kinetics of macronutrient fertilizers coated with manufactured zinc
      oxide nanoparticles.
AB  - The solubility of Zn in Zn fertilizers plays an important role in the agronomic
      effectiveness of the fertilizer. On the basis of thermodynamics, zinc oxide (ZnO)
      nanoparticles (NPs) should dissolve faster and to a greater extent than bulk ZnO
      particles (equivalent spherical diameter >100 nm). These novel solubility
      features of ZnO NPs might be exploited to improve the efficiency of Zn
      fertilizers. In this study, we compared the Zn solubility and dissolution
      kinetics of ZnO nanoparticles and bulk ZnO particles coated onto two selected
      granular macronutrient fertilizers, urea and monoammonium phosphate (MAP). The
      main Zn species on coated MAP and urea granules were zinc ammonium phosphate and
      ZnO, respectively. Coated MAP granules showed greater Zn solubility and faster
      dissolution rates in sand columns compared to coated urea granules, which may be
      related to pH differences in the solution surrounding the fertilizer granules.
      The kinetics of Zn dissolution was not affected by the size of the ZnO particles
      applied for coating of either fertilizer type, possibly because solubility was
      controlled by formation of the same compounds irrespective of the size of the
      original ZnO particles used for coating.

PMID- 22480135
TI  - CLIPS-1D: analysis of multiple sequence alignments to deduce for residue
      positions a role in catalysis, ligand-binding, or protein structure.
AB  - BACKGROUND: One aim of the in silico characterization of proteins is to identify
      all residue-positions, which are crucial for function or structure. Several
      sequence-based algorithms exist, which predict functionally important sites.
      However, with respect to sequence information, many functionally and structurally
      important sites are hard to distinguish and consequently a large number of
      incorrectly predicted functional sites have to be expected. This is why we were
      interested to design a new classifier that differentiates between functionally
      and structurally important sites and to assess its performance on representative
      datasets. RESULTS: We have implemented CLIPS-1D, which predicts a role in
      catalysis, ligand-binding, or protein structure for residue-positions in a
      mutually exclusive manner. By analyzing a multiple sequence alignment, the
      algorithm scores conservation as well as abundance of residues at individual
      sites and their local neighborhood and categorizes by means of a multiclass
      support vector machine. A cross-validation confirmed that residue-positions
      involved in catalysis were identified with state-of-the-art quality; the mean MCC
      value was 0.34. For structurally important sites, prediction quality was
      considerably higher (mean MCC = 0.67). For ligand-binding sites, prediction
      quality was lower (mean MCC = 0.12), because binding sites and structurally
      important residue-positions share conservation and abundance values, which makes
      their separation difficult. We show that classification success varies for
      residues in a class-specific manner. This is why our algorithm computes residue
      specific p-values, which allow for the statistical assessment of each individual
      prediction. CLIPS-1D is available as a Web service at http://www-bioinf.uni
      regensburg.de/. CONCLUSIONS: CLIPS-1D is a classifier, whose prediction quality
      has been determined separately for catalytic sites, ligand-binding sites, and
      structurally important sites. It generates hypotheses about residue-positions
      important for a set of homologous proteins and focuses on conservation and
      abundance signals. Thus, the algorithm can be applied in cases where function
      cannot be transferred from well-characterized proteins by means of sequence
      comparison.

PMID- 22480136
TI  - Assessment of prenatal exposure to tobacco smoke by cotinine in cord blood for
      the evaluation of smoking control policies in Spain.
AB  - BACKGROUND: Over the last few years a decreasing trend in smoking has occurred
      not only in the general population but also during pregnancy. Several countries
      have implemented laws requiring all enclosed workplace and public places to be
      free of second hand smoke (SHS). In Spain, legislation to reduce SHS was
      implemented in 2005. The present study examines the possible effect of this
      legislation on prenatal SHS exposure. METHODS: Mothers and newborns were
      recruited from 3 independent studies performed in Hospital del Mar (Barcelona)
      and approved by the local Ethics Committee: 415 participated in a study in 1996
      1998, 283 in 2002-2004 and 207 in 2008. A standard questionnaire, including
      neonatal and sociodemographic variables,tobacco use and exposure during
      pregnancy, was completed at delivery for all the participants in the three study
      groups. Fetal exposure to tobacco was studied by measuring cotinine in cord blood
      by radioimmunoassay (RIA). RESULTS: 32.8% of the pregnant women reported to smoke
      during pregnancy in 1996-1998, 25.9% in 2002-2004 and 34.1% in 2008. In the most
      recent group, the percentage of no prenatal SHS exposure (cord blood cotinine 0.2
      1 ng/mL) showed an increase compared to the previous groups while the percentages
      of both: low (1.1-14 ng/mL) and very high (> 100 ng/mL) prenatal SHS exposure
      showed a decrease. DISCUSSION: The results of the three study periods (1996-2008)
      demonstrated a significant increase in the percentage of newborns free from SHS
      exposure and a decrease in the percentage of newborns exposed to SHS during
      pregnancy, especially at the very high levels of exposure. A significant maternal
      smoking habit was noted in this geographical area with particular emphasis on
      immigrant pregnant smoking women. CONCLUSIONS: Our study indicates that there is
      a significant maternal smoking habit in this geographical area. Our
      recommendation is that campaigns against smoking should be directed more
      specifically towards pregnant women with particular emphasis on non-native
      pregnant smokers due to the highest prevalence of tobacco consumption in the
      immigrant women.

PMID- 22480137
TI  - In vivo wound-healing efficacy and antioxidant activity of Achyranthes aspera in
      experimental burns.
AB  - CONTEXT: The floral richness of the North-East Indian region cannot be neglected
      in context to its medicinal importance. Achyranthes aspera Linn. (Amaranthaceae;
      Prickly Chaff flower) is an indigenous plant species of this region. Although the
      local traditional healers have ethnomedical knowledge on the use of this plant,
      there is no scientific study on wound-healing activity of this plant. OBJECTIVE:
      The healing efficacy of methanol leaf extract of A. aspera (MEAA) in granulation
      tissue of burn wound and its antioxidant activity are investigated. MATERIALS AND
      METHODS: Methanol extract of leaves of A. aspera was used for compounding 5%
      (w/w) ointment, which was applied topically twice daily in experimental burn
      wound in rats. Healing potential was assessed by rate of wound contraction,
      antioxidant and biochemical assay which was supported by gelatin zymography and
      histopathology. RESULTS: In the present study, 5% ointment of A. aspera showed
      significant (p < 0.05) wound healing, which was evident by wound contraction,
      elevation of various antioxidant enzymes viz. SOD, catalase, vitamin C and
      prohealing and biochemical parameters like hydroxyproline and protein content
      than the control animals. Up-regulated expression of matrix metalloproteinases
      (MMP-2 and 9) was also observed by gelatin zymography. Histopathological
      examination of the granulation tissues in the A. aspera-treated animals showed
      collagen deposition, fibroblast proliferation and formation of epidermis.
      DISCUSSION AND CONCLUSION: The methanol leaf extract of A. aspera showed
      excellent wound-healing activities which has great potential for development of
      plant-based product.

PMID- 22480138
TI  - The live-birth prevalence of mucopolysaccharidoses in Estonia.
AB  - Previous studies on the prevalence of mucopolysaccharidoses (MPS) in different
      populations have shown considerable variations. There are, however, few data with
      regard to the prevalence of MPSs in Fenno-Ugric populations or in north-eastern
      Europe, except for a report about Scandinavian countries. A retrospective
      epidemiological study of MPSs in Estonia was undertaken, and live-birth
      prevalence of MPS patients born between 1985 and 2006 was estimated. The live
      birth prevalence for all MPS subtypes was found to be 4.05 per 100,000 live
      births, which is consistent with most other European studies. MPS II had the
      highest calculated incidence, with 2.16 per 100,000 live births (4.2 per 100,000
      male live births), forming 53% of all diagnosed MPS cases, and was twice as high
      as in other studied European populations. The second most common subtype was MPS
      IIIA, with a live-birth prevalence of 1.62 in 100,000 live births. With 0.27 out
      of 100,000 live births, MPS VI had the third-highest live-birth prevalence. No
      cases of MPS I were diagnosed in Estonia, making the prevalence of MPS I in
      Estonia much lower than in other European populations. MPSs are the third most
      frequent inborn error of metabolism in Estonia after phenylketonuria and
      galactosemia.

PMID- 22480140
TI  - Recurring competitive reactions: desorption of methane and molecular hydrogen
      from Cu(001).
AB  - Methane and molecular hydrogen desorption from a methyl and hydrogen exposed
      Cu(001) surface is investigated. Both gaseous products are observed nearly
      simultaneously within two temperature regimes separated by more than 100 K. The
      lower temperature desorption, at ~325 K, is believed to result from two processes
      which compete for adsorbed atomic hydrogen: methyl reduction and associative
      hydrogen desorption. The higher-temperature competitive desorption is initiated
      after the onset of thermal decomposition of remaining methyl species, at ~420 K.
      Kinetic simulations of the two presumed competing reactions are used to show
      observable and comparable methane and hydrogen evolution can occur in two
      temperature regimes, only with a precise balance of kinetic parameters, but fail
      to accurately reproduce the observed small differences in CH(4) and H(2) peak
      desorption temperatures. It is concluded that either the utilized desorption
      kinetics are inaccurate at low H((a)) coverages or rapid desorption, or the same
      reactions are not competitive at higher temperatures and an alternative active
      mechanism for product evolution must exist.

PMID- 22480139
TI  - Prevalence of the NKG2D Thr72Ala polymorphism in patients with cervical
      carcinoma.
AB  - BACKGROUND: The natural killer group 2, member D (NKG2D) receptor is mainly
      situated on the surface of NK and CD8(+) alphabeta T cells that are involved in
      the defense against viral agents and in cancer immunosurveillance. The G>A
      transition (Thr72Ala) (rs2255336) located in the NKG2D region encoding the
      transmembrane part of this receptor has been associated with decreased
      functionality of NK and T cells. METHODS: Using polymerase chain reaction
      restriction fragment length polymorphisms, we examined the NKG2D Thr72Ala
      polymorphism in patients with cervical cancer (n=353) and controls (n=366) in a
      Polish population. RESULTS: We observed an increased frequency of Thr/Thr or/and
      Thr/Ala genotypes in controls compared with all patients with cervical cancer;
      however, these differences were not significant. We found a significantly
      increased frequency of the NKG2D 72Thr allele in controls than in all patients
      (odds ratio [OR]=0.7410 [95% confidence intervals (CI)=0.5683-0.9662, p=0.0265]).
      Moreover, stratification of patients based on cancer stage showed a significant
      increase in the Thr/Thr genotype frequency (OR=0.3086 [95% CI=0.09097-1.047,
      p=0.0461]), as well as in the Thr/Thr and Thr/Ala genotype frequency (OR=0.4504
      [95% CI=0.2891-0.7018, p=0.0003]), in controls compared with patients with
      cervical cancer in stages III and IV. The frequency of the NKG2D 72Thr allele was
      also significantly increased in controls as compared with patients in stage III
      and IV cancer (OR=0.4699 [95% CI=0.3170-0.6967, p=0.0001]). CONCLUSION: Our
      studies may suggest that the women with cervical cancer bearing the NKG2D 72Thr
      gene variant might be protected against progression to advanced stages of this
      cancer.

PMID- 22480141
TI  - Recurrent fungal iris granuloma in a 10-year-old child.
AB  - PURPOSE: To report the diagnosis of a case of recurrent iris fungal granuloma
      presumed to be an iris tuberculoma in a 10-year-old girl. DESIGN: Case report
      METHODS: Retrospective medical chart review including serological and
      microbiological investigative results RESULTS: A patient presented with iris mass
      associated with anterior uveitis. Serological tests were positive for IgM of
      tuberculosis. Steroids treatment was initiated in conjunction with anti
      tuberculosis treatment. The course showed remissions and exacerbation. Fine
      needle aspiration biopsy (FNAB) of the granuloma proved the etiologic agent to be
      Aspergillus fumigates. CONCLUSION: Fine needle aspiration biopsy should be used
      in the diagnosis of iris masses associated with recurrent inflammation.

PMID- 22480144
TI  - Practitioners' prognoses: potential clinical and/or research tool?

PMID- 22480142
TI  - Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral
      target for hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection has been clinically associated with serum lipid
      abnormalities, yet our understanding of the effects of HCV on host lipid
      metabolism and conversely the function of individual lipids in HCV replication
      remains incomplete. Using liquid chromatography-mass spectrometry metabolite
      profiling of the HCV JFH1 cell culture infection model, we identified a
      significant steady-state accumulation of desmosterol, an immediate precursor to
      cholesterol. Pharmacological inhibition or RNAi-mediated depletion of DHCR7
      significantly reduced steady-state HCV protein expression and viral genomic RNA.
      Moreover, this effect was reversed when cultures were supplemented with exogenous
      desmosterol. Together, these observations suggest an intimate connection between
      HCV replication and desmosterol homeostasis and that the enzymes responsible for
      synthesis of desmosterol may be novel targets for antiviral design.

PMID- 22480145
TI  - Synthesis of Diblock copolymer poly-3-hydroxybutyrate -block-poly-3
      hydroxyhexanoate [PHB-b-PHHx] by a beta-oxidation weakened Pseudomonas putida
      KT2442.
AB  - BACKGROUND: Block polyhydroxyalkanoates (PHA) were reported to be resistant
      against polymer aging that negatively affects polymer properties. Recently, more
      and more attempts have been directed to make PHA block copolymers. Diblock
      copolymers PHB-b-PHHx consisting of poly-3-hydroxybutyrate (PHB) block covalently
      bonded with poly-3-hydroxyhexanoate (PHHx) block were for the first time produced
      successfully by a recombinant Pseudomonas putida KT2442 with its beta-oxidation
      cycle deleted to its maximum. RESULTS: The chloroform extracted polymers were
      characterized by nuclear magnetic resonance (NMR), thermo- and mechanical
      analysis. NMR confirmed the existence of diblock copolymers consisting of 58 mol%
      PHB as the short chain length block with 42 mol% PHHx as the medium chain length
      block. The block copolymers had two glass transition temperatures (Tg) at 2.7
      degrees C and -16.4 degrees C, one melting temperature (Tm) at 172.1 degrees C
      and one cool crystallization temperature (Tc) at 69.1 degrees C as revealed by
      differential scanning calorimetry (DSC), respectively. This is the first
      microbial short-chain-length (scl) and medium-chain-length (mcl) PHA block
      copolymer reported. CONCLUSIONS: It is possible to produce PHA block copolymers
      of various kinds using the recombinant Pseudomonas putida KT2442 with its beta
      oxidation cycle deleted to its maximum. In comparison to a random copolymer poly
      3-hydroxybutyrate-co-3-hydroxyhexanoate (P(HB-co-HHx)) and a blend sample of PHB
      and PHHx, the PHB-b-PHHx showed improved structural related mechanical
      properties.

PMID- 22480146
TI  - The effects of adjuvant insulin therapy among pregnant women with IGT who failed
      to achieve the desired glycemia levels by diet and moderate physical activity.
AB  - OBJECTIVE: Evaluation of adjuvant insulin therapy effects on glycemic control,
      perinatal outcome and postpuerperal glucose tolerance in impaired glucose
      tolerance (IGT) pregnant women who failed to achieve desired glycemic control by
      dietary regime. METHODS: A total of 280 participants were classified in two
      groups: Group A patients continued with dietary regime and Group B patients were
      treated with adjuvant insulin therapy. Glycemic control was assessed by
      laboratory and ultrasonograph means. Pregnancy outcomes were evaluated by
      prevalence of pregnancy induced hypertension (PIH), high birth weight, neonatal
      hypoglycemia and caesarean section rates. Postpuerperal glucose tolerance was
      assessed by oral glucose tolerance test (oGTT). RESULTS: All laboratory and
      ultrasound indicators of glycemic control had significantly lower values in Group
      B. Group A women were more likely to develop the EPH (Edema, Proteinuria,
      Hypertension) syndrome, 20% versus 7.86% (p = 0.003). High birth weight occurred
      more frequently in Group A, but the difference was not significant (p = 0.197).
      Higher rate of caesarean delivery was in Group A than in Group B, 16.43% versus
      26.43% (p = 0.041). The difference in neonatal hypoglycemia was not significant
      (p = 0.478). Pathological oGTT results were observed in 73 Group A patients and
      in 15 Group B patients. CONCLUSION: Lower caesarean section rates and the EPH
      syndrome incidence are the benefits of adjuvant insulin therapy in IGT patients.

PMID- 22480147
TI  - Alliance and termination status in couple therapy: a comparison of methods for
      assessing discrepancies.
AB  - Much of the empirical data available about therapeutic alliance and its
      relationship to termination status come from individual psychotherapies. We know
      less about therapeutic alliance in couple therapy. A unique characteristic of
      alliance in couple or family therapy is the possibility of discrepancies in
      alliance between system members. In this study we sought to demonstrate three
      statistical techniques: standard deviations, the intraclass correlation to assess
      discrepancies in alliance over time during the initial stage of couple therapy,
      and the use of these various measures to predict termination status using a
      sample of 72 couples from a university-based training clinic. Differences in
      partners' alliances operationalized either as categorical or continuous variables
      but when analyzed separately at each time point were not predictive of
      termination status. When multilevel modeling was used, a difference in the way
      the discrepancies changed over a period of time was related to termination
      status.

PMID- 22480148
TI  - Twenty two cases of canine neural angiostronglyosis in eastern Australia (2002
      2005) and a review of the literature.
AB  - Cases of canine neural angiostrongylosis (NA) with cerebrospinal fluid (CSF)
      evaluations in the peer-reviewed literature were tabulated. All cases were from
      Australia. A retrospective cohort of 59 dogs was contrasted with a series of 22
      new cases where NA was diagnosed by the presence of both eosinophilic pleocytosis
      and anti-Angiostrongylus cantonensis immunloglobulins (IgG) in CSF, determined by
      ELISA or Western blot. Both cohorts were drawn from south east Queensland and
      Sydney. The retrospective cohort comprised mostly pups presented for hind limb
      weakness with hyperaesthesia, a mixture of upper motor neurone (UMN) and lower
      motor neurone (LMN) signs in the hind limbs and urinary incontinence. Signs were
      attributed to larval migration through peripheral nerves, nerve roots, spinal
      cord and brain associated with an ascending eosinophilic meningo-encephomyelitis.
      The contemporary cohort consisted of a mixture of pups, young adult and mature
      dogs, with a wider range of signs including (i) paraparesis/proprioceptive ataxia
      (ii) lumbar and tail base hyperaesthesia, (iii) multi-focal central nervous
      system dysfunction, or (iv) focal disease with neck pain, cranial neuropathy and
      altered mentation. Cases were seen throughout the year, most between April and
      July (inclusive). There was a preponderance of large breeds. Often littermates,
      or multiple animals from the same kennel, were affected simultaneously or
      sequentially. A presumptive diagnosis was based on consistent signs, proximity to
      rats, ingestion/chewing of slugs or snails and eosinophilic pleocytosis. NA was
      diagnosed by demonstrating anti-A. cantonensis IgG in CSF. Detecting anti-A.
      cantonensis IgG in serum was unhelpful because many normal dogs (20/21 pound
      dogs; 8/22 of a hospital population) had such antibodies, often at substantial
      titres. Most NA cases in the contemporary series (19/22) and many pups (16/38) in
      the retrospective cohort were managed successfully using high doses of
      prednisolone and opioids. Treatment often included antibiotics administered in
      case protozoan encephalomyelitis or translocated bacterial meningitis was
      present. Supportive measures included bladder care and physiotherapy. Several
      dogs were left with permanent neural deficits. Dogs are an important sentinel
      species for NA. Human cases and numerous cases in tawny frogmouths were reported
      from the same regions as affected dogs over the study period.

PMID- 22480150
TI  - TINA manual landmarking tool: software for the precise digitization of 3D
      landmarks.
AB  - BACKGROUND: Interest in the placing of landmarks and subsequent morphometric
      analyses of shape for 3D data has increased with the increasing accessibility of
      computed tomography (CT) scanners. However, current computer programs for this
      task suffer from various practical drawbacks. We present here a free software
      tool that overcomes many of these problems. RESULTS: The TINA Manual Landmarking
      Tool was developed for the digitization of 3D data sets. It enables the
      generation of a modifiable 3D volume rendering display plus matching orthogonal
      2D cross-sections from DICOM files. The object can be rotated and axes defined
      and fixed. Predefined lists of landmarks can be loaded and the landmarks
      identified within any of the representations. Output files are stored in various
      established formats, depending on the preferred evaluation software. CONCLUSIONS:
      The software tool presented here provides several options facilitating the
      placing of landmarks on 3D objects, including volume rendering from DICOM files,
      definition and fixation of meaningful axes, easy import, placement, control, and
      export of landmarks, and handling of large datasets. The TINA Manual Landmark
      Tool runs under Linux and can be obtained for free from http://www.tina
      vision.net/tarballs/.

PMID- 22480149
TI  - Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen
      receptor negative breast cancer among African-American women: a case-control
      study.
AB  - INTRODUCTION: American women of African ancestry (AA) are more likely than
      European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25
      hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative
      tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well
      as in inherited genetic variations, may contribute, in part, to the differences
      in tumor characteristics. METHODS: In a case (n = 928)-control (n = 843) study of
      breast cancer in AA and EA women, we measured serum 25OHD levels in controls and
      tested associations between risk and tag single nucleotide polymorphisms (SNPs)
      in VDR, CYP24A1 and CYP27B1, particularly by ER status. RESULTS: More AAs had
      severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest
      levels among those with the highest African ancestry. Associations for SNPs
      differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum
      levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53,
      95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The
      majority of associations were for ER-negative breast cancer, with seven
      differential associations between AA and EA women for CYP24A1 (p for interaction
      < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER
      negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no
      effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20
      0.73), with no associations in AAs. The increased risk of ER-negative breast
      cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20,
      95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs. CONCLUSIONS:
      These data suggest that genetic variants in the vitamin D pathway may be related
      to the higher prevalence of ER-negative breast cancer in AA women.

PMID- 22480151
TI  - The role of gene expression profiling in the management of breast cancer
      patients.
AB  - Breast cancer specialists often find it difficult to decide whether or not to
      recommend on chemotherapy in women with presumed low risk for future development
      of metastatic disease. This decision is usually based on well-established
      clinical and histopathological scoring tools. During recent years, an additional
      way to estimate the risk for advanced disease comes from gene expression
      profiling of the breast cancer tumor cells. Such diagnostic tests are already in
      the market and relevant data are quickly accumulating. This article reviews the
      principles of this innovative prognostic system and brings data from the latest
      clinical trials.

PMID- 22480154
TI  - Hallowed by history, but not by facts: "evidence-based" assessments of
      homeopathy.

PMID- 22480152
TI  - A low-cost exon capture method suitable for large-scale screening of genetic
      deafness by the massively-parallel sequencing approach.
AB  - Current major barriers for using next-generation sequencing (NGS) technologies in
      genetic mutation screening on an epidemiological scale appear to be the high
      accuracy demanded by clinical applications and high per-sample cost. How to
      achieve high efficiency in enriching targeted disease genes while keeping a low
      cost/sample is a key technical hurdle to overcome. We validated a cDNA-probe
      based approach for capturing exons of a group of genes known to cause deafness.
      Polymerase chain reaction amplicons were made from cDNA clones of the targeted
      genes and used as bait probes in hybridization for capturing human genomic DNA
      (gDNA) fragments. The cDNA library containing the clones of targeted genes
      provided a readily available, low-cost, and regenerable source for producing
      capture probes with standard molecular biology equipment. Captured gDNA fragments
      by our method were sequenced by the Illumina NGS platform. Results demonstrated
      that targeted exons captured by our approach achieved specificity,
      multiplexicity, uniformity, and depth of coverage suitable for accurate
      sequencing applications by the NGS systems. Reliable genotype calls for various
      homozygous and heterozygous mutations were achieved. The results were confirmed
      independently by conventional Sanger sequencing. The method validated here could
      be readily expanded to include all-known deafness genes for applications such as
      genetic hearing screening in newborns. The high coverage depth and cost benefits
      of the cDNA-probe-based exon capture approach may also facilitate widespread
      applications in clinical practices beyond screening mutations in deafness genes.

PMID- 22480155
TI  - The regioselective switch for amino-NHC mediated C-H activation of benzimidazole
      via Ni-Al synergistic catalysis.
AB  - We have disclosed a new mode of a chemically regioselective switch for C-H bond
      functionalization of benzimidazole derivatives via a cooperative effect invoked
      by Ni-Al bimetallic catalysis to create a steric requirement for obtaining the
      linear product of styrene insertion. Yet, excluding the AlMe(3) cocatalyst
      switches the reaction toward branch selectivity.

PMID- 22480156
TI  - Spectroscopic studies of bridge contributions to electronic coupling in a donor
      bridge-acceptor biradical system.
AB  - Variable-temperature electronic absorption and resonance Raman spectroscopies are
      used to probe the excited state electronic structure of Tp(Cum,Me)Zn(SQ-Ph-NN)
      (1), a donor-bridge-acceptor (D-B-A) biradical complex and a ground state
      analogue of the charge-separated excited state formed in photoinduced electron
      transfer reactions. Strong electronic coupling mediated by the p-phenylene bridge
      stabilizes the triplet ground state of this molecule. Detailed spectroscopic and
      bonding calculations elucidate key bridge distortions that are involved in the
      SQ(pi)(SOMO) -> NN-Ph (pi*)(LUMO) D -> A charge transfer (CT) transition. We show
      that the primary excited state distortion that accompanies this CT is along a
      vibrational coordinate best described as a symmetric Ph(8a) + SQ(in-plane) linear
      combination and underscores the dominant role of the phenylene bridge fragment
      acting as an electron acceptor in the D-B-A charge transfer state. Our results
      show the importance of the phenylene bridge in promoting (1) electron transfer in
      D-Ph-A systems and (2) electron transport in biased electrode devices that employ
      a 1,4-phenylene linkage. We have also developed a relationship between the spin
      density on the acceptor, as measured via the isotropic NN nitrogen hyperfine
      interaction, and the strength of the D -> A interaction given by the magnitude of
      the electronic coupling matrix element, H(ab).

PMID- 22480157
TI  - India's rare inland mangroves deserve protection.

PMID- 22480158
TI  - Comment on uridine diphosphate glucuronosyltransferase isoform-dependent
      regiospecificity of glucuronidation of flavonoids: applicability of UV spectrum
      shifts in identification of glucuronidation position in flavones and flavonols.

PMID- 22480159
TI  - Control of the coordination status of the open metal sites in metal-organic
      frameworks for high performance separation of polar compounds.
AB  - Metal-organic frameworks (MOFs) with open metal sites have great potential for
      enhancing adsorption separation of the molecules with different polarities.
      However, the elution and separation of polar compounds on such MOFs packed
      columns using nonpolar solvents is difficult due to too strong interaction
      between polar compounds and the open metal sites. Here, we report the control of
      the coordination status of the open metal sites in MOFs by adjusting the content
      of methanol (MeOH) in the mobile phase for fast and high-resolution separation of
      polar compounds. To this end, high-performance liquid chromatographic separation
      of nitroaniline, aminophenol and naphthol isomers, sulfadimidine, and
      sulfanilamide on the column packed with MIL-101(Cr) possessing open metal sites
      was performed. The interaction between the open metal sites of MIL-101(Cr) and
      the polar analytes was adjusted by adding an appropriate amount of MeOH to the
      mobile phase to achieve the effective separation of the polar analytes due to the
      competition of MeOH with the analytes for the open metal sites. Fourier transform
      infrared spectra and X-ray photoelectron spectra confirmed the interaction
      between MeOH and the open metal sites of MIL-101(Cr). Thermodynamic parameters
      were measured to evaluate the effect of the content of MeOH in the mobile phase
      on the separation of polar analytes on MIL-101(Cr) packed column. This approach
      provides reproducible and high performance separation of polar compounds on the
      open metal sites-containing MOFs.

PMID- 22480160
TI  - GABA receptor ameliorates ventilator-induced lung injury in rats by improving
      alveolar fluid clearance.
AB  - INTRODUCTION: Mechanical ventilators are increasingly used in critical care
      units. However, they can cause lung injury, including pulmonary edema. Our
      previous studies indicated that gamma-aminobutyric acid (GABA) receptors are
      involved in alveolar-fluid homeostasis. The present study investigated the role
      of GABA receptors in ventilator-induced lung injury. METHODS: Adult female
      Sprague-Dawley rats were subjected to high-tidal-volume ventilation of 40 ml/kg
      body weight for 1 hour, and lung injuries were assessed. RESULTS: High-tidal
      volume ventilation resulted in lung injury, as indicated by an increase in total
      protein in bronchoalveolar fluid, wet-to-dry ratio (indication of pulmonary
      edema), and Evans Blue dye extravasation (indication of vascular damage).
      Intratracheal administration of GABA before ventilation significantly reduced the
      wet-to-dry ratio. Further, histopathologic analysis indicated that GABA reduced
      ventilator-induced lung injury and apoptosis. GABA-mediated reduction was
      effectively blocked by the GABAA-receptor antagonist, bicuculline. The GABA
      mediated effect was not due to the vascular damage, because no differences in
      Evans Blue dye extravasation were noted. However, the decrease in alveolar fluid
      clearance by high-tidal-volume ventilation was partly prevented by GABA, which
      was blocked by bicuculline. CONCLUSIONS: These results suggest that GABA reduces
      pulmonary edema induced by high-tidal-volume ventilation via its effects on
      alveolar fluid clearance and apoptosis.

PMID- 22480161
TI  - Bias-stress effect in 1,2-ethanedithiol-treated PbS quantum dot field-effect
      transistors.
AB  - We investigate the bias-stress effect in field-effect transistors (FETs)
      consisting of 1,2-ethanedithiol-treated PbS quantum dot (QD) films as charge
      transport layers in a top-gated configuration. The FETs exhibit ambipolar
      operation with typical mobilities on the order of MU(e) = 8 * 10(-3) cm(2) V(-1)
      s(-1) in n-channel operation and MU(h) = 1 * 10(-3) cm(2) V(-1) s(-1) in p
      channel operation. When the FET is turned on in n-channel or p-channel mode, the
      established drain-source current rapidly decreases from its initial magnitude in
      a stretched exponential decay, manifesting the bias-stress effect. The choice of
      dielectric is found to have little effect on the characteristics of this bias
      stress effect, leading us to conclude that the associated charge-trapping process
      originates within the QD film itself. Measurements of bias-stress-induced time
      dependent decays in the drain-source current (I(DS)) are well fit to stretched
      exponential functions, and the time constants of these decays in n-channel and p
      channel operation are found to follow thermally activated (Arrhenius) behavior.
      Measurements as a function of QD size reveal that the stressing process in n
      channel operation is faster for QDs of a smaller diameter while stress in p
      channel operation is found to be relatively invariant to QD size. Our results are
      consistent with a mechanism in which field-induced nanoscale morphological
      changes within the QD film result in screening of the applied gate field. This
      phenomenon is entirely recoverable, which allows us to repeatedly observe bias
      stress and recovery characteristics on the same device. This work elucidates
      aspects of charge transport in chemically treated lead chalcogenide QD films and
      is of relevance to ongoing investigations toward employing these films in
      optoelectronic devices.

PMID- 22480162
TI  - Experimental and GIAO 15N NMR study of substituent effects in 1H-tetrazoles.
AB  - A series of 1-aryl/alkyl-1H-1,2,3,4-tetrazoles, 5-substituted 1H-tetrazoles, and
      1,5- and 2,5-disubstituted 1H-tetrazoles were studied by a combination of
      experimental NMR (natural abundance (15)N, (15)N/(1)H HMBC, and (13)C) and
      computational GIAO-NMR techniques to explore substituent effects on (15)N (and
      (13)C) NMR chemical shifts in the tetrazole (TA) moiety. Computed (15)N chemical
      shifts via GIAO-B3LYP/6-311+G(2d,p) calculations gave satisfactory results in
      comparison with experimental data. Whereas N-alkylation leads to large (15)N
      chemical shift changes, changes in the N(1)-aryl derivatives bearing diverse
      substituent(s) are generally small except for polar ortho-substituents (COOH,
      NO(2)). Large Deltadelta(15)N values were computed in N(1)-aryl derivatives for p
      COH(2)(+) and p-OMeH(+) as extreme examples of electron-withdrawing substituents
      on a TA moiety.

PMID- 22480163
TI  - The effects of a fixed combination of 0.5% timolol and 1% dorzolamide on optic
      nerve head blood circulation.
AB  - PURPOSE: The purpose of the present study is to evaluate the effects of a fixed
      combination of 0.5% timolol maleate (TM) and 1% dorzolamide hydrochloride (DZ)
      (FCTD(1%)) on optic nerve head (ONH) blood circulation. SUBJECTS AND METHODS: A
      drop of 0.5% TM, 1% DZ, or FCTD(1%) was topically administered to the right eyes
      of 15 healthy Japanese subjects, and a drop of saline was likewise administrated
      to their left eyes. Systemic blood pressure, heart rates (HRs), intraocular
      pressures (IOPs), ocular perfusion pressures, and blood circulation by a laser
      speckle flowgraphy at the ONH were measured before administration, and again at
      1.5 and 6 h afterward. RESULTS: FCTD(1%) caused a significant increase in ONH
      blood circulation 6 h after the administration, while 0.5% TM and 1% DZ had no
      significant effect. The IOPs were significantly decreased in 0.5% TM (P<0.01) and
      FCTD(1%) (P<0.05) when compared with the saline-treated eyes at 1.5 and 6 h after
      administration, while 1% DZ did not show a statistically significant decrease.
      There were no significant changes in other systemic parameters except for a
      significant transient decrease in the HRs observed in 0.5% TM (P<0.01) when
      compared with the baseline at 1.5 h after the administration. CONCLUSION: Our
      current results suggest that FCTD(1%) caused a significant increase in ocular
      blood circulation on the ONH in healthy Japanese subjects, presumably by a
      synergistic effect of 0.5% TM and 1% DZ, although neither 0.5% TM nor 1% DZ on
      their own had a significant effect.

PMID- 22480164
TI  - The impact of CPR and AED training on healthcare professionals' self-perceived
      attitudes to performing resuscitation.
AB  - BACKGROUND: Healthcare professionals have shown concern about performing mouth-to
      mouth ventilation due to the risks to themselves with the procedure. However,
      little is known about healthcare professionals' fears and attitudes to start CPR
      and the impact of training. OBJECTIVE: To examine whether there were any changes
      in the attitudes among healthcare professionals to performing CPR from before to
      after training. METHODS: Healthcare professionals from two Swedish hospitals were
      asked to answer a questionnaire before and after training. The questions were
      relating to physical and mental discomfort and attitudes to CPR. Statistical
      analysis used was generalized McNemar's test. RESULTS: Overall, there was
      significant improvement in 10 of 11 items, reflecting various aspects of
      attitudes to CPR. All groups of health care professionals (physicians, nurses,
      assistant nurses, and "others" = physiotherapists, occupational therapists,
      social welfare officers, psychologists, biomedical analysts) felt more secure in
      CPR knowledge after education. In other aspects, such as anxiety prior to a
      possible cardiac arrest, only nurses and assistant nurses improved.The concern
      about being infected, when performing mouth to mouth ventilation, was reduced
      with the most marked reduction in physicians (75%; P < 0.001). CONCLUSION: In
      this hospital-based setting, we found a positive outcome of education and
      training in CPR concerning healthcare professionals' attitudes to perform CPR.
      They felt more secure in their knowledge of cardiopulmonary resuscitation. In
      some aspects of attitudes to resuscitation nurses and assistant nurses appeared
      to be the groups that were most markedly influenced. The concern of being
      infected by a disease was low.

PMID- 22480165
TI  - Disruption of the folate pathway in zebrafish causes developmental defects.
AB  - BACKGROUND: Folic acid supplementation reduces the risk of neural tube defects
      and congenital heart defects. The biological mechanisms through which folate
      prevents birth defects are not well understood. We explore the use of zebrafish
      as a model system to investigate the role of folate metabolism during
      development. RESULTS: We first identified zebrafish orthologs of 12 human folate
      metabolic genes. RT-PCR and in situ analysis indicated maternal transcripts
      supply the embryo with mRNA so that the embryo has an intact folate pathway. To
      perturb folate metabolism we exposed zebrafish embryos to methotrexate (MTX), a
      potent inhibitor of dihydrofolate reductase (Dhfr) an essential enzyme in the
      folate metabolic pathway. Embryos exposed to high doses of MTX exhibited
      developmental arrest prior to early segmentation. Lower doses of MTX resulted in
      embryos with a shortened anterior-posterior axis and cardiac defects: linear
      heart tubes or incomplete cardiac looping. Inhibition of dhfr mRNA with antisense
      morpholino oligonucleotides resulted in embryonic lethality. One function of the
      folate pathway is to provide essential one-carbon units for dTMP synthesis, a
      rate-limiting step of DNA synthesis. After 24 hours of exposure to high levels of
      MTX, mutant embryos continue to incorporate the thymidine analog BrdU. However,
      additional experiments indicate that these embryos have fewer mitotic cells, as
      assayed with phospho-histone H3 antibodies, and that treated embryos have
      perturbed cell cycles. CONCLUSIONS: Our studies demonstrate that human and
      zebrafish utilize similar one-carbon pathways. Our data indicate that folate
      metabolism is essential for early zebrafish development. Zebrafish studies of the
      folate pathway and its deficiencies could provide insight into the underlying
      etiology of human birth defects and the natural role of folate in development.

PMID- 22480166
TI  - Mutations increased overexpression of Notch1 in T-cell acute lymphoblastic
      leukemia.
AB  - BACKGROUND: The Notch signaling pathway is crucial in T-cell development, Notch1
      mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL).
      To investigate the feature of Notch1 mutation and its corresponding expression
      level in Chinese patients with T-ALL, detection of mutation and the expression
      level of Notch1 gene was preformed using RT-PCR, sequencing and real-time PCR
      respectively. RESULTS: Two Notch1 point mutations (V1578E and L1593P) located on
      HD-N domain were identified in three cases out of 13 T-ALL patients. The mutation
      on 4733 position (V1578E) found in two cases was a novel mutation. The
      overexpression of Notch1 was detected in all samples with T-ALL, moreover,
      significantly higher expression of Notch1 was detected in the T-ALL with Notch1
      mutation group compared with T-ALL with WT Notch1 group (p = 0.0192).
      CONCLUSIONS: Higher expression of Notch1 was associated with Notch1 mutation,
      more novel mutation of this gene might be identified in different populations and
      its contribution to the molecular pathogenesis of T-ALL is needed further
      research.

PMID- 22480167
TI  - Novel materials which possess the ability to target liver cells.
AB  - INTRODUCTION: Hepatic-targeted drug delivery systems are designed to treat
      diseases of the liver. However, since there are several different types of liver
      diseases that are caused by different cells, it is important to select the proper
      materials to target these different cells. AREAS COVERED: This review addresses
      novel materials that possess the ability to target liver cells via receptor
      ligand processes and offers an insight into the aspects of formulation design. It
      also discusses several approaches used to enhance the targeting efficiency of
      drug delivery systems to receptors in the liver cells. In addition, the delivery
      efficiency and therapeutic efficacy of these materials in the treatment of acute
      or chronic liver diseases is highlighted. EXPERT OPINION: Further research into
      the use of clinical materials and the design of smart materials for multi-drug
      delivery to different organelles is important for future studies on these new
      materials. It is hoped that these targeted therapeutics will benefit patients
      with liver disorders in the near future.

PMID- 22480169
TI  - Relative sensitivities of Japanese quail to foreign red blood cell challenges for
      immunotoxicity testing.
AB  - Given evidence that the immune system is sensitive to environmental contaminants,
      evaluating immunocompetence in toxicology studies is increasingly important. By
      incorporating a test of humoral response into controlled reproductive and
      developmental studies, more comprehensive results can be gathered to assess the
      potential for disease. The foreign red blood cells (RBC) challenge is a minimally
      invasive method for evaluating humoral responses to a foreign antigen. Typically,
      antibody response is assessed following injections of sheep erythrocytes;
      however, Japanese quail (Coturnix japonica) are only minimally sensitive to sheep
      RBC. In the present study, adult Japanese quail were treated with 5% solutions of
      RBC from goose, goat, cow, donkey, or pig in primary and secondary challenges.
      After each treatment, plasma samples were taken and antibody responses were
      measured for total immunoglobulins (Ig), IgG, and IgM. Overall, goose RBC
      generated the poorest responses in both primary and secondary challenges, while
      the strongest antibody responses were to pig and donkey RBC. Therefore, pig RBC
      appear to be a superior antigen for testing humoral response in Japanese quail.

PMID- 22480168
TI  - Diesel exhaust particulate induces pulmonary and systemic inflammation in rats
      without impairing endothelial function ex vivo or in vivo.
AB  - BACKGROUND: Inhalation of diesel exhaust impairs vascular function in man, by a
      mechanism that has yet to be fully established. We hypothesised that pulmonary
      exposure to diesel exhaust particles (DEP) would cause endothelial dysfunction in
      rats as a consequence of pulmonary and systemic inflammation. METHODS: Wistar
      rats were exposed to DEP (0.5 mg) or saline vehicle by intratracheal instillation
      and hind-limb blood flow, blood pressure and heart rate were monitored in situ 6
      or 24 h after exposure. Vascular function was tested by administration of the
      endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium
      independent vasodilator sodium nitroprusside (SNP) in vivo and ex vivo in
      isolated rings of thoracic aorta, femoral and mesenteric artery from DEP exposed
      rats. Bronchoalveolar lavage fluid (BALF) and blood plasma were collected to
      assess pulmonary (cell differentials, protein levels & interleukin-6 (IL-6)) and
      systemic (IL-6), tumour necrosis factor alpha (TNFalpha) and C-reactive protein
      (CRP)) inflammation, respectively. RESULTS: DEP instillation increased cell
      counts, total protein and IL-6 in BALF 6 h after exposure, while levels of IL-6
      and TNFalpha were only raised in blood 24 h after DEP exposure. DEP had no effect
      on the increased hind-limb blood flow induced by ACh in vivo at 6 or 24 h.
      However, responses to SNP were impaired at both time points. In contrast, ex vivo
      responses to ACh and SNP were unaltered in arteries isolated from rats exposed to
      DEP. CONCLUSIONS: Exposure of rats to DEP induces both pulmonary and systemic
      inflammation, but does not modify endothelium-dependent vasodilatation. Other
      mechanisms in vivo limit dilator responses to SNP and these require further
      investigation.

PMID- 22480170
TI  - Expression analysis of hepatic mitochondria-related genes in mice exposed to
      acrylamide and glycidamide.
AB  - Acrylamide (AA) is an industrial chemical that has been extensively investigated
      for central nervous system (CNS), reproductive, and genetic toxicity. However, AA
      effects on the liver, a major organ of drug metabolism, have not been adequately
      explored. In addition, the role of mitochondria in AA-mediated toxicity is still
      unclear. Changes in expression levels of genes associated with hepatic
      mitochondrial function of male transgenic Big Blue (BB) mice administered 500
      mg/L AA or an equimolar concentration (600 mg/L) of its reactive metabolite
      glycidamide (GA) in drinking water for 3 and 4 wk, respectively, were examined.
      Transcriptional profiling of 542 mitochondria-related genes indicated a
      significant downregulation of genes associated with the 3-beta-hydroxysteroid
      dehydrogenase family in AA- and GA-treated mice, suggesting a possible role of
      both chemicals in altering hepatic steroid metabolism in BB mice. In addition,
      genes associated with lipid metabolism were altered by both treatments.
      Interestingly, only the parental compound (AA) significantly induced expression
      levels of genes associated with oxidative phosphorylation, in particular ATP
      synthase, which correlated with elevated ATP levels, indicating an increased
      energy demand in liver during AA exposure. Acrylamide-treated mice also showed
      significantly higher activity of glutathione S-transferase in association with
      decreased levels of reduced glutathione (GSH), which may imply an enhanced rate
      of conjugation of AA with GSH in liver. These results suggest different hepatic
      mechanisms of action of AA and GA and provide important insights into the
      involvement of mitochondria during their exposures.

PMID- 22480171
TI  - Trihalomethanes in drinking water and the risk of death from kidney cancer: does
      hardness in drinking water matter?
AB  - The objectives of this study were to (1) examine the relationship between total
      trihalomethanes (TTHM) levels in public water supplies and risk of development of
      kidney cancer and (2) determine whether hardness levels in drinking water modify
      the effects of TTHM on risk of kidney cancer induction. A matched case-control
      study was used to investigate the relationship between the risk of death
      attributed to kidney cancer and exposure to TTHM in drinking water in 53
      municipalities in Taiwan. All kidney cancer deaths in the 53 municipalities from
      1998 through 2007 were obtained. Controls were deaths from other causes and were
      pair-matched to the cancer cases by gender, year of birth, and year of death.
      Each matched control was selected randomly from the set of possible controls for
      each cancer case. Data on TTHM levels and levels of hardness in drinking water
      were also collected. The municipality of residence for cancer cases and controls
      was presumed to be the source of the subject's TTHM and hardness exposure via
      drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb,
      the adjusted OR (95% CI) for kidney cancer was 0.98 (0.77-1.25) for individuals
      who resided in municipalities served by drinking water with a TTHM exposure >=4.9
      ppb. However, evidence of an interaction was noted between the use of soft water
      and drinking water TTHM concentrations. Increased knowledge of the interaction
      between hardness and TTHM levels in reducing risk of kidney cancer development
      will aid in public policy decision and establishing standards to prevent disease
      occurrence.

PMID- 22480172
TI  - Effects of Libby amphibole asbestos exposure on two models of arthritis in the
      Lewis rat.
AB  - Epidemiological data suggest that occupational exposure to the amphibole
      containing vermiculite in Libby, MT, was associated with increased risk for
      developing autoimmune diseases and had an odds ratio of 3.23 for developing
      rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) and the
      peptidoglycan-polysaccharide (PG-PS) models of RA were employed to determine
      whether exposure to Libby amphibole (LA) induced a more rapid onset, increased
      expression, or prolonged course of RA. Female Lewis rats were intratracheally
      instilled with total doses of 0.15, 0.5, 1.5, or 5 mg LA or 0.5 or 1.5 mg amosite
      asbestos, and arthritis was induced with either the PG-PS or CIA model. Neither
      LA nor amosite exposure affected the disease course in the CIA model, or the
      production of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)
      antibodies. LA exposure reduced swelling in the PG-PS model and decreased anti-PG
      PS and total immunoglobulin M (IgM) antibody titers. Both amosite and LA exposure
      increased the number of rats with circulating anti-nuclear antibodies (ANA), the
      majority of which presented a speckled staining pattern. However, this ANA
      enhancement was not dose responsive. These results failed to show a positive
      correlation between LA exposure and RA disease in two animal models, although
      upregulated ANA suggest an altered immunological profile consistent with other
      systemic autoimmune diseases.

PMID- 22480174
TI  - Cisplatin disrupts the latency of human herpesvirus 8 and induces apoptosis in
      primary effusion lymphoma cells.
AB  - Human herpesvirus 8 (HHV8) is the etiologic agent for primary effusion lymphoma
      (PEL). The aim of this study is to investigate the effects of cisplatin on the
      PEL cells. Cisplatin treatment induced apoptosis and inhibited the growth of PEL
      cells, and the effect was more profound in the HHV8-positive lymphoma cells
      compared with the EBV-positive lymphoma cells. Cisplatin treatment decreased the
      expression of HHV8 latent genes and activated p53 at serine 15 in PEL cells. Our
      results indicate that cisplatin can disrupt HHV8 latency and induce reactivation
      of p53 and highly selective treatment modality for this virally induced lymphoma.

PMID- 22480175
TI  - Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside
      induced lipid peroxidation in rat pancreas by water extractable phytochemicals
      from some tropical spices.
AB  - CONTEXT: Spices have been used as food adjuncts and in folklore for ages.
      Inhibition of key enzymes (alpha-amylase and alpha-glucosidase) involved in the
      digestion of starch and protection against free radicals and lipid peroxidation
      in pancreas could be part of the therapeutic approach towards the management of
      hyperglycemia and dietary phenolics have shown promising potentials. OBJECTIVE:
      This study investigated and compared the inhibitory properties of aqueous
      extracts of some tropical spices: Xylopia aethiopica [Dun.] A. Rich (Annonaceae),
      Monodora myristica (Gaertn.) Dunal (Annonaceae), Syzygium aromaticum [L.] Merr.
      et Perry (Myrtaceae), Piper guineense Schumach. et Thonn (Piperaceae), Aframomum
      danielli K. Schum (Zingiberaceae) and Aframomum melegueta (Rosc.) K. Schum
      (Zingiberaceae) against alpha-amylase, alpha-glucosidase, 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radicals and sodium nitroprusside (SNP)-induced lipid
      peroxidation in rat pancreas--in vitro using different spectrophotometric method.
      MATERIALS AND METHODS: Aqueous extract of the spices was prepared and the ability
      of the spice extracts to inhibit alpha-amylase, alpha-glucosidase, DPPH radicals
      and SNP-induced lipid peroxidation in rat pancreas--in vitro was investigated
      using various spectrophotometric methods. RESULT: All the spice extracts
      inhibited alpha-amylase (IC(50) = 2.81-4.83 mg/mL), alpha-glucosidase (IC(50) =
      2.02-3.52 mg/mL), DPPH radicals (EC(50) = 15.47-17.38 mg/mL) and SNP-induced
      lipid peroxidation (14.17-94.38%), with the highest alpha-amylase & alpha
      glucosidase inhibitory actions and DPPH radical scavenging ability exhibited by
      X. aethiopica, A. danielli and S. aromaticum, respectively. Also, the spices
      possess high total phenol (0.88-1.3 mg/mL) and flavonoid (0.24-0.52 mg/mL)
      contents with A. melegueta having the highest total phenolic and flavonoid
      contents. DISCUSSION AND CONCLUSION: The inhibitory effects of the spice extracts
      on alpha-amylase, alpha-glucosidase, DPPH radicals and SNP-induced lipid
      peroxidation in pancreas (in vitro) could be attributed to the presence of
      biologically active phytochemicals such as phenolics and some non-phenolic
      constituents of the spices. Furthermore, these spices may exert their anti
      diabetic properties through the mechanism of enzyme inhibition, free radicals
      scavenging ability and prevention of lipid peroxidation.

PMID- 22480173
TI  - Resection of the primary tumour versus no resection prior to systemic therapy in
      patients with colon cancer and synchronous unresectable metastases (UICC stage
      IV): SYNCHRONOUS--a randomised controlled multicentre trial (ISRCTN30964555).
AB  - BACKGROUND: Currently, it remains unclear, if patients with colon cancer and
      synchronous unresectable metastases who present without severe symptoms should
      undergo resection of the primary tumour prior to systemic chemotherapy. Resection
      of the primary tumour may be associated with significant morbidity and delays the
      beginning of chemotherapy. However, it may prevent local symptoms and may,
      moreover, prolong survival as has been demonstrated in patients with metastatic
      renal cell carcinoma. It is the aim of the present randomised controlled trial to
      evaluate the efficacy of primary tumour resection prior to systemic chemotherapy
      to prolong survival in patients with newly diagnosed colon cancer who are not
      amenable to curative therapy. METHODS/DESIGN: The SYNCHRONOUS trial is a
      multicentre, randomised, controlled, superiority trial with a two-group parallel
      design. Colon cancer patients with synchronous unresectable metastases are
      eligible for inclusion. Exclusion criteria are primary tumour-related symptoms,
      inability to tolerate surgery and/or systemic chemotherapy and history of another
      primary cancer. Resection of the primary tumour as well as systemic chemotherapy
      is provided according to the standards of the participating institution. The
      primary endpoint is overall survival that is assessed with a minimum follow-up of
      36 months. Furthermore, it is the objective of the trial to assess the safety of
      both treatment strategies as well as quality of life. DISCUSSION: The SYNCHRONOUS
      trial is a multicentre, randomised, controlled trial to assess the efficacy and
      safety of primary tumour resection before beginning of systemic chemotherapy in
      patients with metastatic colon cancer not amenable to curative therapy. TRIAL
      REGISTRATION: ISRCTN30964555.

PMID- 22480176
TI  - The Diels-Alder cyclization of ketenimines.
AB  - A Diels-Alder reaction between cyclopentadiene and a variety of ketenimines is
      reported. A copper(I)-bis(phosphine complex catalyzes the cycloaddition across
      the C?N bond of the ketenimine in a [4 + 2] reaction to give an enamine
      intermediate that is hydrolyzed upon purification to generate aminoketones.

PMID- 22480177
TI  - The relationship between single nucleotide polymorphisms in 5-HT2A signal
      transduction-related genes and the response efficacy to selective serotonin
      reuptake inhibitor treatments in Chinese patients with major depressive disorder.
AB  - OBJECTIVE: To explore the possible relationship between six single nucleotide
      polymorphisms (SNPs) (rs6311 and rs6305 of 5-HT2A, rs5443 of Gbeta3, rs2230739 of
      ACDY9, rs1549870 of PDE1A and rs255163 of CREB1, which are all related with 5
      HT2A the signal transduction pathway) and the response efficacy to selective
      serotonin reuptake inhibitor (SSRI) treatments in major depressive disorder (MDD)
      Chinese. METHODS: This study included 194 depressed patients to investigate the
      influence of 6 polymorphisms in 5-HT2A signal transduction-related genes on the
      efficacy of SSRIs assessed over 1 year. The efficacies of SSRIs on 194 MDD
      patients were evaluated in an 8-week open-trial study. Over 1 year, a follow-up
      study was completed for 174 of them to observe the long-term efficacy of SSRIs.
      The optimal-scaling regression analysis was used for testing the relationship
      between the different genotypes of five SNPs and the efficacy in MDD. RESULTS: It
      showed that the patients with rs5443TT and rs2230739GG have a relatively good
      efficacy in response to short-term SSRIs. We also found that good efficacy
      appeared in depressed patients with rs2230739GG in response to long-term SSRIs.
      CONCLUSIONS: It suggested that different genotypes of rs5443 and rs2230739 might
      influence the signal transduction pathways of second message and affect
      therapeutic efficacy.

PMID- 22480178
TI  - An engineered lantibiotic synthetase that does not require a leader peptide on
      its substrate.
AB  - Ribosomally synthesized and post-translationally modified peptides are a rapidly
      expanding class of natural products. They are typically biosynthesized by
      modification of a C-terminal segment of the precursor peptide (the core peptide).
      The precursor peptide also contains an N-terminal leader peptide that is required
      to guide the biosynthetic enzymes. For bioengineering purposes, the leader
      peptide is beneficial because it allows promiscuous activity of the biosynthetic
      enzymes with respect to modification of the core peptide sequence. However, the
      leader peptide also presents drawbacks as it needs to be present on the core
      peptide and then removed in a later step. We show that fusing the leader peptide
      for the lantibiotic lacticin 481 to its biosynthetic enzyme LctM allows the
      protein to act on core peptides without a leader peptide. We illustrate the use
      of this methodology for preparation of improved lacticin 481 analogues containing
      non-proteinogenic amino acids.

PMID- 22480179
TI  - Efficient synthesis of a chiral precursor for angiotensin-converting enzyme (ACE)
      inhibitors in high space-time yield by a new reductase without external
      cofactors.
AB  - A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate
      (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral
      precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For
      the first time, (R)-HPBE with >99% ee was produced via bioreduction of OPBE at 1
      M without external addition of cofactors. The space-time yield (700 g.L(-1).d(
      1)) was 27 times higher than the highest record.

PMID- 22480180
TI  - Substrate-induced changes in the dynamics of rhodopsin kinase (G protein-coupled
      receptor kinase 1).
AB  - G protein-coupled receptor (GPCR) kinases (GRKs) instigate the desensitization of
      activated GPCRs via phosphorylation that promotes interaction with arrestins,
      thereby preventing the interaction of GPCRs with heterotrimeric G proteins. A
      current proposed model of GRK1 activation involves the binding of activated
      rhodopsin (Rho*) to the N-terminal region of GRK1. Perhaps concomitantly, this N
      terminal region also stabilizes a closed, active conformation of the kinase
      domain. To further probe this model, we mapped changes in the backbone
      flexibility of GRK1 as it binds to its two substrates, adenosine triphosphate
      (Mg(2+).ATP) and Rho*. We found that the conformational flexibility of GRK1 was
      reduced in the presence of either Mg(2+).ATP or Rho*, with Mg(2+).ATP having the
      greatest effect. In a truncated form of GRK1 lacking the N-terminal region
      (DeltaN-GRK1), peptides that directly interact with ATP were not as dramatically
      stabilized by adding Mg(2+).ATP, and dynamics were greater in the interface
      between the large lobe of the kinase domain and the regulator of the G protein
      signaling homology domain. In the presence of Mg(2+).ATP, the influence of Rho*
      versus Rho on GRK1 dynamics was negligible.

PMID- 22480181
TI  - Ionic strength and pH as control parameters for spontaneous surface oscillations.
AB  - A system far from equilibrium, where the surfactant transfer from a small drop
      located in the aqueous bulk to the air-water interface results in spontaneous
      nonlinear oscillations of surface tension, is theoretically and experimentally
      considered. The oscillations in this system are the result of periodically
      arising and terminating Marangoni instability. The surfactant under consideration
      is octanoic acid, the dissociated form of which is much less surface-active than
      the protonated form. Numerical simulations show how the system behavior can be
      controlled by changes in pH and ionic strength of the aqueous phase. The results
      of numerical simulations are in good agreement with experimental data.

PMID- 22480182
TI  - Non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase:
      synthesis, structure-activity relationships, and pharmacokinetics.
AB  - The measles virus (MeV), a member of the paramyxovirus family, is an important
      cause of pediatric morbidity and mortality worldwide. In an effort to provide
      therapeutic treatments for improved measles management, we previously identified
      a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA
      polymerase by means of high-throughput screening. Subsequent structure-activity
      relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold
      led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar
      potency against life MeV and attractive physical properties suitable for
      development. However, its poor water solubility and low oral bioavailability (F)
      in rat suggested that the lead could benefit from further SAR studies to improve
      the biophysical characteristics of the compound. Optimization of in vitro potency
      and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent
      inhibitor of MeV (EC(50) = 60 nM) with an aqueous solubility of approximately 60
      MUg/mL. The agent shows a 10-fold exposure (AUC/C(max)) increase in the rat model
      relative to 2, displays near dose proportionality in the range of 10-50 mg/kg,
      and exhibits good oral bioavailability (F = 39%). The significant solubility
      increase appears linked to the improved oral bioavailability.

PMID- 22480184
TI  - CD4 T cell depletion exacerbates acute Mycobacterium tuberculosis while
      reactivation of latent infection is dependent on severity of tissue depletion in
      cynomolgus macaques.
AB  - CD4 T cells are believed to be important in protection against Mycobacterium
      tuberculosis, but the relative contribution to control of initial or latent
      infection is not known. Antibody-mediated depletion of CD4 T cells in M.
      tuberculosis-infected cynomolgus macaques was used to study the role of CD4 T
      cells during acute and latent infection. Anti-CD4 antibody severely reduced
      levels of CD4 T cells in blood, airways, and lymph nodes. Increased pathology and
      bacterial burden were observed in CD4-depleted monkeys during the first 8 weeks
      of infection compared to controls. CD4-depleted monkeys had greater interferon
      (IFN)-gamma expression and altered expression of CD8 T cell activation markers.
      During latent infection, CD4 depletion resulted in clinical reactivation in only
      three of six monkeys. Reactivation was associated with lower CD4 T cells in the
      hilar lymph nodes. During both acute and latent infection, CD4 depletion was
      associated with reduced percentages of CXCR3(+) expressing CD8 T cells, reported
      to be involved in T cell recruitment, regulatory function, and effector and
      memory T cell maturation. CXCR3(+) CD8 T cells from hilar lymph nodes had more
      mycobacteria-specific cytokine expression and greater coexpression of multiple
      cytokines compared to CXCR3(-) CD8 T cells. CD4 T cells are required for
      protection against acute infection but reactivation from latent infection is
      dependent on the severity of depletion in the draining lymph nodes. CD4 depletion
      influences CD8 T cell function. This study has important implications for human
      HIV-M. tuberculosis coinfection.

PMID- 22480185
TI  - Higher fine-scale genetic structure in peripheral than in core populations of a
      long-lived and mixed-mating conifer--eastern white cedar (Thuja occidentalis L.).
AB  - BACKGROUND: Fine-scale or spatial genetic structure (SGS) is one of the key
      genetic characteristics of plant populations. Several evolutionary and ecological
      processes and population characteristics influence the level of SGS within plant
      populations. Higher fine-scale genetic structure may be expected in peripheral
      than core populations of long-lived forest trees, owing to the differences in the
      magnitude of operating evolutionary and ecological forces such as gene flow,
      genetic drift, effective population size and founder effects. We addressed this
      question using eastern white cedar (Thuja occidentalis) as a model species for
      declining to endangered long-lived tree species with mixed-mating system.
      RESULTS: We determined the SGS in two core and two peripheral populations of
      eastern white cedar from its Maritime Canadian eastern range using six nuclear
      microsatellite DNA markers. Significant SGS ranging from 15 m to 75 m distance
      classes was observed in the four studied populations. An analysis of combined
      four populations revealed significant positive SGS up to the 45 m distance class.
      The mean positive significant SGS observed in the peripheral populations was up
      to six times (up to 90 m) of that observed in the core populations (15 m).
      Spatial autocorrelation coefficients and correlograms of single and sub-sets of
      populations were statistically significant. The extent of within-population SGS
      was significantly negatively correlated with all genetic diversity parameters.
      Significant heterogeneity of within-population SGS was observed for 0-15 m and 61
      90 m between core and peripheral populations. Average Sp, and gene flow distances
      were higher in peripheral (Sp = 0.023, sigmag = 135 m) than in core (Sp = 0.014,
      sigmag = 109 m) populations. However, the mean neighborhood size was higher in
      the core (Nb = 82) than in the peripheral (Nb = 48) populations. CONCLUSION:
      Eastern white cedar populations have significant fine-scale genetic structure at
      short distances. Peripheral populations have several-folds higher within
      population fine-scale genetic structure than core populations. Anthropogenic
      disturbances and population fragmentation presumably have significant effects on
      fine-scale genetic structure in eastern white cedar. Core populations have higher
      neighborhood size than peripheral populations, whereas gene flow distances are
      higher in peripheral than in core populations. The results of our study
      contribute to the knowledge of poorly-understood spatial genetic structure of
      core versus peripheral populations in plants. As well, the information is of
      significance for conservation of genetic resources of eastern white cedar and
      perhaps of other long-lived forest trees with mixed-mating system.

PMID- 22480186
TI  - Changes in the levels of cytokines, chemokines and malaria-specific antibodies in
      response to Plasmodium falciparum infection in children living in sympatry in
      Mali.
AB  - BACKGROUND: The Fulani are known to be less susceptible to Plasmodium falciparum
      malaria as reflected by lower parasitaemia and fewer clinical symptoms than other
      sympatric ethnic groups. So far most studies in these groups have been performed
      on adults, which is why little is known about these responses in children. This
      study was designed to provide more information on this gap. METHODS: Circulating
      inflammatory factors and antibody levels in children from the Fulani and Dogon
      ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta,
      IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines;
      regulated on activation normal T cell expressed and secreted (RANTES), monokine
      induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma
      inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of
      interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin
      (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA. RESULTS: The
      results revealed that the Fulani children had higher levels of all tested
      cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be
      involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was
      increased in the Fulani compared to the Dogon. When dividing the children into
      infected and uninfected individuals, infected Dogon had significantly lower
      levels of RANTES compared to their uninfected peers, and significantly higher
      levels of MIG and IP-10 as well as MCP-1, although the latter did not reach
      statistical significance. In contrast, such patterns were not seen in the
      infected Fulani children and their chemokine levels remained unchanged upon
      infection compared to uninfected counterparts. Furthermore, the Fulani also had
      higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses
      compared to the Dogon. CONCLUSIONS: Taken together, this study demonstrates, in
      accordance with previous work, that Fulani children mount a stronger inflammatory
      and antibody response against P. falciparum parasites compared to the Dogon and
      that these differences are evident already at an early age. The inflammatory
      responses in the Fulani were not influenced by an active infection which could
      explain why less clinical symptoms are seen in this group.

PMID- 22480187
TI  - Moderate glucose control results in less negative nitrogen balances in medical
      intensive care unit patients: a randomized, controlled study.
AB  - INTRODUCTION: Hyperglycemia and protein loss are common in critically ill
      patients. Insulin can be used to lower blood glucose and inhibit proteolysis. The
      impact of moderate insulin therapy on protein metabolism in critically ill
      patients has not been evaluated. We compared urinary nitrogen excretion, nitrogen
      balance, serum albumin concentrations, prealbumin concentrations, and clinical
      outcomes between patients receiving moderate insulin therapy (MIT) and
      conventional insulin therapy (CIT) in a medical ICU. METHODS: Patients were
      randomly divided into groups and treated with MIT (glucose target 120 to 140
      mg/dl) or CIT (glucose target 180 to 200 mg/dl). Calories and protein intake were
      recorded each day. On days 3, 7 and 14, the 24-hour urinary nitrogen excretion,
      nitrogen balance, and serum albumin and prealbumin concentrations were measured.
      Clinical outcomes data were collected. RESULTS: A total of 112 medical ICU
      patients were included, with 55 patients randomized to the MIT group and 57
      patients randomized to the CIT group. Patients treated with MIT showed a trend
      towards increased nitrogen balance (P = 0.070), significantly lower urinary
      nitrogen excretion (P = 0.027), and higher serum albumin (P = 0.047) and
      prealbumin (P = 0.001) concentrations than patients treated with CIT. The
      differences between the two groups were most significant on day 3, when all
      factors showed significant differences (P < 0.05). CONCLUSIONS: Moderate glucose
      control results in less negative nitrogen balances in medical ICU patients.
      Differences are more significant in the early stages compared with the late
      stages of critical illness. TRIAL REGISTRATION: ClinicalTrial.Gov NCT 01227148.

PMID- 22480188
TI  - Comparison between scaling-root-planing (SRP) and SRP/photodynamic therapy: six
      month study.
AB  - INTRODUCTION: The purpose of this long-term clinical study was to examine the
      additional efficacy of photodynamic therapy (PDT) to scaling and root planing
      (SRP) in patients with chronic periodontal disease. METHODS: A total of 22
      patients (mean age: 59.3 +/- 11.7 years) with chronic periodontal disease and
      four teeth with probing depth >= 5 mm were enrolled in the study. Inclusion
      criteria were: no systemic disease, no smoking, no pregnancy and no long-term
      medication. Beside the anamnesis, the following clinical parameters were assessed
      at baseline (one week before therapy), and one, three and six months after the
      therapy: bleeding on probing (BOP), plaque index (PI) probing depth (PD), and
      clinical attachment loss. All measurements were done by the same examiner with a
      fixed periodontal probe (PCP 12, Hu-Friedy) at six measurements/tooth. In each
      patient, two teeth were treated with SRP alone and two teeth with SRP and PDT
      (Periowave, Ondine Biopharma, Vancouver, Canada). The nonparametric Wilcoxon test
      for paired samples was used for comparison of the effect of the two treatments (p
      <= 0.05). RESULTS: After both types of treatment, the number of teeth positive
      for BOP declined. At baseline, the CAL measured 7.2 +/- 1.2 mm (SRP) or 8.1 +/-
      1.3 mm (SRP/PDT); one, three and six months after both types of treatment an
      improvement was observed. At baseline, the probing depth was 5.9 +/- 0.8 mm (SRP)
      or 6.4 +/- 0.8 mm (SRP/PDT); after six months, an improvement of 2.4 +/- 0.6 mm
      (SRP) or 2.9 +/- 0.8 mm (SRP/PDT) was found. The greater reduction of the PD,
      achieved by a combination of SRP/PDT, was statistically significant after six
      months (p = 0.007). CONCLUSION: This clinical study demonstrates that SRP in
      combination with PDT seems to be effective and is therefore suitable as an
      adjuvant therapy to the mechanical conditioning of the periodontal pockets in
      patients with chronic periodontal diseases.

PMID- 22480189
TI  - A randomized controlled trial of CBT therapy for adults with ADHD with and
      without medication.
AB  - BACKGROUND: Previous studies of psychological treatment in adults with ADHD have
      not controlled for medication status and include either medicated participants or
      mixed samples of medicated and unmedicated participants. The objective of this
      study is to examine whether use of medication improves outcome of therapy.
      METHOD: This was a secondary analysis comparing 23 participants randomized to CBT
      and Dextroamphetamine vs. 25 participants randomized to CBT and placebo. Both
      patients and investigators were blind to treatment assignment. Two co-primary
      outcomes were used: ADHD symptoms on the ADHD-RS-Inv completed by the
      investigator and improvement in functioning as reported by the patient on the
      Sheehan Disability Scale. RESULTS: Both groups showed robust improvement in both
      symptoms and functioning, but the use of medication did not significantly improve
      outcome over and above use of CBT and placebo. CONCLUSION: This study replicates
      previous work demonstrating that CBT is an effective treatment for ADHD in
      adults. Within the limits of this pilot, secondary analysis we were not able to
      demonstrate that medication significantly augments the outcome of CBT therapy for
      adults with ADHD. The study was funded by GlaxoSmithKline, Clinical Trials
      Registry #GSK707.

PMID- 22480190
TI  - Mechanism and enzymatic contribution to in vitro test method of digestion for
      maize starches differing in amylose content.
AB  - To determine the rapidly digestible starch (RDS), slowly digestible starch (SDS),
      and resistant starch (RS) contents in a starch sample, the addition of
      amyloglucosidase is often used to convert hydrolyzates from alpha-amylase
      digestion to glucose. The objectives of this study were to investigate the exact
      role of amyloglucosidase in determining the digestibility of starch and to
      understand the mechanism of enzymatic actions on starch granules. Four maize
      starches differing in amylose content were examined: waxy maize (0.5% amylose),
      normal maize (~27% amylose), and two high-amylose starches (~57 and ~71%
      amylose). Notably, without amyloglucosidase addition, the RS content increased
      from 4.3 to 74.3% for waxy maize starch, 29.7 to 76.5% for normal maize starch,
      65.8 to 88.0% for starch with 57% amylose, and 68.2 to 90.4% for the starch with
      71% amylose. In the method without alpha-amylase addition, less RS was produced
      than without added amyloglucosidase, except in maize at 71% amylose content.
      Scanning electron microscopy (SEM) revealed the digestive patterns of pinholes
      with alpha-amylase and burrowing with amyloglucosidase as well as the degree of
      digestion between samples. To understand the roles of amyloglucosidase and alpha
      amylase in the in vitro test, multiple analytical techniques including gel
      permeation chromatography, SEM, synchrotron wide-angle X-ray diffraction, and
      small-angle X-ray scattering were used to determine the molecular and crystalline
      structure before and after digestion. Amyloglucosidase has a significant impact
      on the SDS and RS contents of granular maize starches.

PMID- 22480192
TI  - Palladium-catalyzed intermolecular cyclocarbonylation of 2-iodoanilines with the
      Michael acceptor, diethyl ethoxycarbonylbutendienoate.
AB  - Palladium-catalyzed intermolecular cyclocarbonylation of 2-iodoanilines with
      diethyl ethoxycarbonylbutendienoate produces 2,3,3-triethoxycarbonyl-2,3-dihydro
      4(1H)-quinolinone derivatives in moderate to good yields. This protocol involves
      Michael addition and subsequent carbonylation.

PMID- 22480191
TI  - P53 gene mutation increases progastrin dependent colonic proliferation and colon
      cancer formation in mice.
AB  - Transgenic mice overexpressing human progastrin (hGAS) show colonic crypt hyper
      proliferation and elevated susceptibility to colon carcinogenesis. We aimed to
      investigate effects of p53 mutation on colon carcinogenesis in hGAS mice. We show
      that introducing a p53 gene mutation further increases progastrin dependent BrdU
      labeling and results in markedly elevated number of aberrant crypt foci (ACF) and
      colonic tumors. We demonstrate that hGAS/Lgr5-GFP mice have higher number of
      Lgr5+ colonic stem cells per crypt when compared to Lgr5-GFP mice indicating that
      progastrin changes crypt biology through increased stem cell numbers and
      additional p53 mutation leads to more aggressive phenotype in this murine colon
      cancer model.

PMID- 22480193
TI  - Atomic force microscopy (AFM)-based nanografting for the study of self-assembled
      monolayer formation of organophosphonic acids on Al2O3 single-crystal surfaces.
AB  - Adsorption, stability, and organization kinetics of organophosphonic acids on
      single-crystalline alumina surfaces were investigated by means of atomic force
      microscopy (AFM)-based imaging, nanoshaving, and nanografting. AFM friction and
      phase imaging have shown that chemical etching and subsequent annealing led to
      heterogeneities on single-crystalline surfaces with (0001) orientation. Self
      assembly and stability of octadecylphosphonic acid (ODPA) were shown to be
      strictly dependent upon the observed heterogeneities of the surface termination,
      where it was locally shown that ODPA can loosely or strongly bind on different
      terminations of the crystal surface. Organization kinetics of ODPA was monitored
      with nanografting on (0001) surfaces. Supported by measurements of surface
      wettability and diffuse reflectance infrared Fourier transform spectroscopy
      (DRIFTS), it was demonstrated that the lack of organization within the protective
      adsorbed hexylphosphonic acid (HPA) monolayer on alumina surfaces facilitated the
      reduced confinement effect during nanografting, such that kinetics information on
      the organization process of ODPA could be obtained.

PMID- 22480194
TI  - Solid-state 13C NMR investigations of cyclophanes: [2.2]paracyclophane and 1,8
      dioxa[8](2,7)pyrenophane.
AB  - Solid-state NMR (ssNMR) and ab initio quantum mechanical calculations are used in
      order to understand and to better characterize the molecular conformation and
      properties of [2.2]paracyclophane and 1,8-dioxa[8](2,7)pyrenophane. Both
      molecules are cyclophanes, consisting of an aromatic ring assembly and a cyclic
      aliphatic chain connected to both ends of the aromatic portion. The aliphatic
      chain causes curvature in the six-membered aromatic ring structures. This led us
      to examine how the ring strain due to curvature affects the chemical shifts.
      Using X-ray structures of both [2.2]paracyclophane and 1,8
      dioxa[8](2,7)pyrenophane as our starting model, we calculate the chemical
      shielding tensors and compare these data with those collected from the (13)C
      ssNMR FIREMAT experiment. We define curvature of [2.2]paracyclophane and 1,8
      dioxa[8](2,7)pyrenophane using the pi-orbital axis vector (POAV) pyramidalization
      angle (theta(p)).

PMID- 22480196
TI  - Shale gas and hydrofracturing.

PMID- 22480195
TI  - ISL1 common variant rs1017 is not associated with susceptibility to congenital
      heart disease in a Chinese population.
AB  - BACKGROUND: ISL1, as a member of the LIM homeodomain transcription factor family,
      is expressed in a distinct population of undifferentiated cardiac progenitors and
      plays a pivotal role in cardiogenesis. Lacking ISL1 expression results in growth
      arrest or displays profound defects in heart development, including atria,
      ventricle, and the inflow and outflow tracts, which constitute a major form of
      congenital heart disease (CHD). Recently, an important study by Stevens et al.
      found that genetic variation in ISL1 is associated with risk of CHD in white and
      black/African American populations; this observation led us to hypothesize that
      ISL1 common variants might influence susceptibility to sporadic CHD in our
      Chinese population. METHODS: We conducted a case-control study of CHD in Chinese
      to test our hypothesis by genotyping ISL1 common variant rs1017 in 1003 CHD cases
      and 1012 non-CHD controls. RESULTS: We found that rs1017 was not associated with
      the risk of CHD (p=0.213). When we performed stratified analyses according to
      subjects' age, sex, and CHD classifications, we found no overall heterogeneity of
      risk in different subgroups. CONCLUSIONS: This is the first study which indicates
      that ISL1 common variant rs1017 may not play a role in sporadic CHD
      susceptibility in the Chinese population.

PMID- 22480197
TI  - Identification of small molecule inhibitors of the HIV-1 nucleocapsid-stem-loop 3
      RNA complex.
AB  - Stem-loop 3 RNA (SL3) in psi-RNA is a highly conserved motif in different strains
      of HIV-1 and serves as a principle determinant for viral packaging. Viral
      encapsulation is critical for viral replication, and disruption of the
      nucleocapsid-psi-RNA complex interferes with viral replication. We have used SL3
      RNA as a target for identification of small molecule inhibitors of the
      interactions of nucleocapsid protein (NCp7) and psi-RNA. We report the use of
      computational and high-throughput screening approaches to identify 16 compounds
      that bind SL3 RNA with micromolar affinities. Among the identified ligands, two
      molecules, compounds 7 and 17, bind with higher affinity to SL3 RNA than to
      double- and single-stranded RNAs. Four of the 16 SL3 RNA ligands inhibit
      interactions between SL3 RNA and NCp7 with micromolar inhibition constants. In
      general, the identified SL3 ligands have simple molecular structures and low
      molecular weights and are, therefore, possible lead compounds for the development
      of ligands that target the elements of psi-RNA of HIV-1 with high affinity and
      specificity.

PMID- 22480198
TI  - Abstracts of the Thirty-Second Annual Meeting of the Surgical Infection Society.
      Dallas, Texas, USA. April 18-21, 2012.

PMID- 22480199
TI  - Commercial Carlinae radix herbal drug: botanical identity, chemical composition
      and antimicrobial properties.
AB  - CONTEXT: Carlinae radix is an herbal drug, commonly used by the locals in
      southeastern Serbia for the treatment of respiratory and urogenital diseases and,
      externally, for various skin conditions. There still seems to be no detailed
      studies correlating the chemical composition of this drug and its
      ethnopharmacological uses. OBJECTIVE: Chemical composition, antimicrobial
      activity and mode of action of C. radix essential oil, isolated from commercial
      samples (confirmation of whose true biological identity was also the aim of this
      work) were analyzed. Antimicrobial potential of decoctions (extracts prepared by
      boiling plant material in a given solvent), used in ethnomedicine preferentially
      to the pure essential oil, was also investigated. MATERIALS AND METHODS: The
      essential oil obtained by hydrodistillation was screened for antimicrobial
      activity by disc diffusion and broth microdilution methods. Effects of the oil on
      the growth of Staphylococcus aureus cells were investigated using turbidimetric
      measurements and visualized using scanning electron microscopy. Analyses of the
      chemical composition of the oils were done using gas chromatography and gas
      chromatography/mass spectrometry. RESULTS AND DISCUSSION: Both the essential oil
      and the decocts exhibited a very high antimicrobial activity against all tested
      strains, with S. aureus as the most sensitive one [e.g., for the oil sample the
      values for minimal inhibitory concentration (MIC) and minimal bactericidal
      concentration (MBC) were 0.02, 0.04 uL/mL, respectively]. Growth curves of S.
      aureus demonstrated a significant decrease in turbidity (for the MIC
      concentration this amounted to ca. 70%) showing a concentration-dependent lysis
      of the cells, confirmed by scanning electron microscopy. Chemical composition,
      anatomical and morphological features of the sample pointed to Carlina
      acanthifolia L. (Asteraceae) instead of Carlina acaulis L. (Asteraceae).
      CONCLUSION: The results showed significant antimicrobial effect of the essential
      oil and the decoctions and support the use of this plant in ethnomedicine for the
      treatment of various human infections, especially those caused by S. aureus.
      Adulteration of the drug would not cause significant differences in its
      biological activity, since chemical composition of the sample showed high
      similarity with those containing C. acaulis roots.

PMID- 22480200
TI  - Intramolecular sila-Matteson rearrangement: a general access to silylated
      heterocycles.
AB  - A series of new silylated heterocycles has been efficiently prepared using an
      intramolecular silicon version of the Matteson rearrangement, providing two
      isomers of binuclear heterocycles. This method applies to a large variety of
      substrates, a direct relationship between the Hammett constants of the aromatic
      substituents and the isomer ratio being observed. Complementary experiments
      suggest that a common pentaorganosilicate species is involved.

PMID- 22480201
TI  - Kidney dysfunction, cardiorespiratory fitness, and the risk of death in women.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of
      cardiovascular (CV) events and death. However, the effect of cardiorespiratory
      fitness on the CKD-mortality relationship remains unknown, particularly in women.
      METHODS: We used Cox regression to estimate hazard ratios (HR) for the effect of
      kidney function and fitness on all-cause mortality in a prospective cohort of
      5716 women free of CKD and CV disease symptoms. Serum creatinine (Cr) was used to
      estimate glomerular filtration rate (eGFR), and spot urine protein and maximal
      stress tests were performed at baseline. RESULTS: Mean age at baseline was 52.5+/
      10.8 years, and 86% of the sample was Caucasian. Mean Cr was 1.11+/-0.14 mg/dL,
      and mean eGFR was 53.7+/-8.3 mL/min/1.73 m(2) at baseline. The mean follow-up was
      15.9+/-2.2 years, with 589 deaths identified. Cr <1.4 was associated with an HR
      of death of 1.59 (p=0.03). After adjustment for traditional CV risk factors and
      fitness, the risk of death decreased by 3% (p<0.001) for every mL/min/1.73 m(2)
      increase in eGFR. Compared to women with an eGFR <45 mL/min/1.73 m(2), the risk
      of death was reduced by 36% and 47%, for eGFR 45-59.9 mL/min/1.73 m(2) and eGFR
      >=60 mL/min/1.73 m(2), respectively (p<0.001). At every level of eGFR, fitness
      remained an independent predictor of mortality, with the lowest level of fitness
      (<5 metabolic equivalents [METs]) at the highest risk of mortality regardless of
      eGFR level. CONCLUSIONS: Fitness remains an independent predictor of mortality
      regardless of eGFR. eGFR was a stronger predictor of mortality compared to Cr or
      the presence of proteinuria. These findings have important implications for
      clinical practice and health policy, as the level of cardiorespiratory fitness
      predicts risk of death in the presence of asymptomatic CKD.

PMID- 22480202
TI  - Structure-based classification and ontology in chemistry.
AB  - BACKGROUND: Recent years have seen an explosion in the availability of data in
      the chemistry domain. With this information explosion, however, retrieving
      relevant results from the available information, and organising those results,
      become even harder problems. Computational processing is essential to filter and
      organise the available resources so as to better facilitate the work of
      scientists. Ontologies encode expert domain knowledge in a hierarchically
      organised machine-processable format. One such ontology for the chemical domain
      is ChEBI. ChEBI provides a classification of chemicals based on their structural
      features and a role or activity-based classification. An example of a structure
      based class is 'pentacyclic compound' (compounds containing five-ring
      structures), while an example of a role-based class is 'analgesic', since many
      different chemicals can act as analgesics without sharing structural features.
      Structure-based classification in chemistry exploits elegant regularities and
      symmetries in the underlying chemical domain. As yet, there has been neither a
      systematic analysis of the types of structural classification in use in chemistry
      nor a comparison to the capabilities of available technologies. RESULTS: We
      analyze the different categories of structural classes in chemistry, presenting a
      list of patterns for features found in class definitions. We compare these
      patterns of class definition to tools which allow for automation of hierarchy
      construction within cheminformatics and within logic-based ontology technology,
      going into detail in the latter case with respect to the expressive capabilities
      of the Web Ontology Language and recent extensions for modelling structured
      objects. Finally we discuss the relationships and interactions between
      cheminformatics approaches and logic-based approaches. CONCLUSION: Systems that
      perform intelligent reasoning tasks on chemistry data require a diverse set of
      underlying computational utilities including algorithmic, statistical and logic
      based tools. For the task of automatic structure-based classification of chemical
      entities, essential to managing the vast swathes of chemical data being brought
      online, systems which are capable of hybrid reasoning combining several different
      approaches are crucial. We provide a thorough review of the available tools and
      methodologies, and identify areas of open research.

PMID- 22480203
TI  - Shear and extensional rheology of cellulose/ionic liquid solutions.
AB  - In this study, we characterize the shear and extensional rheology of dilute to
      semidilute solutions of cellulose in the ionic liquid 1-ethyl-3-methylimidazolium
      acetate (EMIAc). In steady shear flow, the semidilute solutions exhibit shear
      thinning, and the high-frequency complex modulus measured in small amplitude
      oscillatory shear flow exhibits the characteristic scaling expected for solutions
      of semiflexible chains. Flow curves of the steady shear viscosity plotted against
      shear rate closely follow the frequency dependence of the complex viscosity
      acquired using oscillatory shear, thus satisfying the empirical Cox-Merz rule. We
      use capillary thinning rheometry (CaBER) to characterize the relaxation times and
      apparent extensional viscosities of the semidilute cellulose solutions in a
      uniaxial extensional flow that mimics the dynamics encountered in the spin-line
      during fiber spinning processes. The apparent extensional viscosity and
      characteristic relaxation times of the semidilute cellulose/EMIAc solutions
      increase dramatically as the solutions enter the entangled concentration regime
      at which fiber spinning becomes viable.

PMID- 22480204
TI  - A randomized, double blind, placebo and active comparator controlled pilot study
      of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical
      origin.
AB  - BACKGROUND: Current use of prescribed or over the counter non-steroidal anti
      inflammatory drugs (NSAIDs) for pain and osteoarthritis (OA) have untoward
      gastrointestinal and cardiovascular related side effects, as a result the need
      for a safe and effective alternative has become unequivocally crucial. METHOD: A
      randomized, double blind, placebo and active controlled pilot study of a novel
      dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical
      origin, UP446 was conducted. Sixty subjects (age 40-75) with symptomatic OA of
      the hip or knee were assigned to 4 treatment groups (n = 15); Group A0 (Placebo,
      CMC capsule), Group A1 (UP446 250 mg/day), Group A2 (UP446 500 mg/day) and Group
      A3 (Celecoxib, 200 mg/day). MOS-SF-36 and Western Ontario and McMaster University
      Osteoarthritis Index (WOMAC) data were collected at baseline and after 30, 60 and
      90 days of treatment as a measure of efficacy. Erythrocyte sedimentation rate, C
      reactive protein, plasma thrombin time (PTT), fructosamine, Hematology, clinical
      chemistry and fecal occult blood were monitored for safety. RESULTS:
      Statistically significant decrease in WOMAC pain score were observed for Group A1
      at day 90, Group A2 at 30 and 90 days and Group A3 at 60 and 90 days.
      Statistically significant decrease in WOMAC stiffness score were observed for
      Group A1 and Group A2 at 30, 60 and 90 days; but not for Group A0 and Group A3.
      The mean change in WOMAC functional impairment scores were statistically
      significant for Group A1 and Group A2 respectively at 30 days (p = 0.006 and p =
      0.006), at 60 days (p = 0.016 and p = 0.002) and at 90 days (p = 0.018 and p =
      0.002), these changes were not significant for Group A0 and Group A3. Based on
      MOS -SF-36 questionnaires, statistically significant improvements in physical
      function, endurance and mental health scores were observed for all active
      treatment groups compared to placebo. No significant changes suggestive of
      toxicity in routine hematologies, serum chemistries, liver enzymes or PTT were
      noted in any of the treatment groups. CONCLUSION: Based on current findings UP446
      is safe and efficacious alternative to established anti-inflammatory medications
      for alleviating OA symptoms as measured by the WOMAC Index.

PMID- 22480205
TI  - Concurrent binding and delivery of proteins and lipophilic small molecules using
      polymeric nanogels.
AB  - Supramolecular nanoassemblies, which are capable of binding and delivering either
      lipophilic small molecules or hydrophilic molecules, are of great interest.
      Concurrently binding and delivering this combination of molecules is cumbersome,
      because of the opposing supramolecular host requirements. We describe the
      development of a versatile nanoassembly system that is capable of binding and
      delivering both, a protein and a lipophilic small molecule, simultaneously inside
      the cells.

PMID- 22480206
TI  - Clinical features of TTR-FAP in Portugal.
AB  - Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder
      characterized by the extracellular deposition of transthyretin (TTR) fibrils in
      several tissues, particularly in the peripheral nervous system. The largest focus
      of the disease is in Portugal where the age of disease onset shows a wide range
      (17-78 years), with 80% of cases developing symptoms before age 40. The
      characteristic fiber length-dependent sensory-motor and autonomic neuropathy are
      the neurological hallmark of TTR-FAP. Additional cardiovascular, gastrointestinal
      (GI), renal and ocular symptoms are the main systemic manifestations that account
      for phenotypic heterogeneity.

PMID- 22480207
TI  - Transesophageal echocardiography, more than a diagnostic tool: use during
      surgical ligation of coronary artery fistulae - a case report.
AB  - Coronary artery fistulae (CAF) are an infrequent coronary abnormality. Herein, we
      describe the use of intraoperative transesophageal echocardiography (TEE) in the
      treatment of CAF. A 61 year-old woman presented with chest pain and symptoms
      consistent with unstable angina. Subsequent coronary angiography revealed the
      presence of 2 CAF, one extending from the left anterior descending artery to the
      pulmonary artery (PA) and the other extending from the proximal right coronary
      artery to the PA. Surgical ligation of the CAF without coronary bypass was
      arranged. Intraoperative TEE was successfully employed to localize the CAF,
      monitor fistula blood flow and heart wall motion, and confirm successful
      ligation. The patient recovered without complications. This case highlights the
      utility of intraoperative TEE during ligation of CAF.

PMID- 22480208
TI  - Factors associated with history of drug use among female sex workers (FSW) in a
      high HIV prevalence state of India.
AB  - BACKGROUND: The intersection between illicit drug use and female commercial sex
      work has been identified as an important factor responsible for rising HIV
      prevalence among female sex workers (FSW) in several northeastern states of
      India. But, little is know about the factors associated with the use of drugs
      among FSWs in this region. The objective of the paper was to describe the factors
      associated with history of drug use among FSWs in Dimapur, an important
      commercial hub of Nagaland, which is a high HIV prevalence state of India.
      METHODS: FSWs were recruited using respondent driven sampling (RDS), and were
      interviewed to collect data on socio-demographic characteristics and HIV risk
      behaviours. Biological samples were tested for HIV, syphilis gonorrhea and
      Chlamydia. Logistic regression analysis was performed to identify factors
      associated with drug use. RESULTS: Among the 426 FSWs in the study, about 25% (n
      = 107) reported having ever used illicit drugs. Among 107 illicit drug users, 83
      (77.6%) were non-injecting and 24 (22.4%) were injecting drug users. Drug-using
      FSWs were significantly more likely to test positive for one or more STIs (59%
      vs. 33.5%), active syphilis (27.1% vs. 11.4%) and Chlamydia infection (30% vs.
      19.9%) compared to their non-drug using peers. Drug-using FSWs were also
      significantly more likely to be currently married, widowed or separated compared
      with non-drug-using FSWs. In multiple logistic regression analysis, being an
      alcohol user, being married, having a larger volume of clients, and having sexual
      partners who have ever used or shared injecting drugs were found to be
      independently associated with illicit drug use. CONCLUSIONS: Drug-using FSWs were
      more vulnerable to STIs including HIV compared to their non-drug using peers.
      Several important factors associated with being an FSW who uses drugs were
      identified in this study and this knowledge can be used to plan more effectively
      targeted harm reduction strategies and programs.

PMID- 22480209
TI  - Selection and identification of a DNA aptamer targeted to Vibrio parahemolyticus.
AB  - A whole-bacterium systemic evolution of ligands by exponential enrichment (SELEX)
      method was applied to a combinatorial library of FAM-labeled single-stranded DNA
      molecules to identify DNA aptamers demonstrating specific binding to  Vibrio
      parahemolyticus . FAM-labeled aptamer sequences with high binding affinity to  V.
      parahemolyticus  were identified by flow cytometric analysis. Aptamer A3P, which
      showed a particularly high binding affinity in preliminary studies, was chosen
      for further characterization. This aptamer displayed a dissociation constant
      (K(d)) of 16.88 +/- 1.92 nM. Binding assays to assess the specificity of aptamer
      A3P showed a high binding affinity (76%) for  V. parahemolyticus  and a low
      apparent binding affinity (4%) for other bacteria. Whole-bacterium SELEX is a
      promising technique for the design of aptamer-based molecular probes for
      microbial pathogens that does not require the labor-intensive steps of isolating
      and purifying complex markers or targets.

PMID- 22480210
TI  - Plasma membrane calcium ATPase expression in human colon multistep
      carcinogenesis.
AB  - The expression of the plasma membrane Ca(2+) ATPase (PMCA) was analyzed in a
      series of 84 formalin-fixed and paraffin embedded colon samples including normal
      mucosa (n = 32), adenoma (n = 19), adenocarcinoma (n = 27), and lymph node
      metastasis (n = 6) using (i) immunohistochemistry, (ii) mRNA in situ
      hybridization, and (iii) quantitative reverse-transcriptase PCR. A marked
      reduction of PMCA4 protein was observed in high-grade adenoma, colon cancer as
      well as lymph node metastasis, pointing to its potential role in the progression
      of cancer. However, PMCA4 RNA transcripts were unchanged or even increased in
      colon carcinomas, suggesting posttranscriptional regulation of PMCA4 during
      carcinogenesis.

PMID- 22480211
TI  - Association between GNRHR, LHR and IGF1 polymorphisms and timing of puberty in
      male Angus cattle.
AB  - BACKGROUND: In bovines, there are significant differences within and among beef
      breeds in the time when bulls reach puberty. Although the timing of puberty is
      likely to be a multigenic trait, previous studies indicate that there may also be
      single genes that exert major effects on the timing of puberty within the general
      population. Despite its economic importance, there are not many SNPs or genetic
      markers associated with the age of puberty in male cattle. In the present work,
      we selected three candidate genes, GNRHR, LHR and IGF1, and associated their
      polymorphisms with the age of puberty in Angus male cattle. RESULTS: After
      weaning, 276 Angus males were measured every month for weight (W), scrotal
      circumference (SC), sperm concentration (C) and percentage of motility (M). A
      total of 4 SNPs, two within GNRHR, one in LHR and one in IGF1 were genotyped
      using the pyrosequencing technique. IGF1-SnaBI SNP was significant associated (P
      < 0.01) with age at SC 28 cm, but it were not associated with age at M 10% and C
      50 million. Genotype CC exhibited an average age at SC 28 cm of 7 and 11 days
      higher than CT (p = 0.037) and TT (p = 0.012), respectively. This SNP explained
      1.5% of the genetic variance of age of puberty at SC28. LHR-I499L, GNRHR-SNP5 and
      GNRHR-SNP6 were not associated with any of the measurements. However, GNRHR
      haplotypes showed a suggestive association with age at SC 28 cm. CONCLUSIONS: The
      findings presented here could support the hypothesis that IGF1 is a regulator of
      the arrival to puberty in male calves and is involved in the events that precede
      and initiate puberty in bull calves. Given that most studies in cattle, as well
      as in other mammals, were done in female, the present results are the first
      evidence of markers associated with age at puberty in male cattle.

PMID- 22480212
TI  - Micropatterning of bioactive glass nanoparticles on chitosan membranes for
      spatial controlled biomineralization.
AB  - Bioactive glass nanoparticles (BG-NPs) capable of inducing apatite precipitation
      upon immersion in simulated body fluid (SBF) were patterned on free-standing
      chitosan membranes by microcontact printing using a poly(dimethylsiloxane) (PDMS)
      stamp inked in a BG-NPs pad. Formation of the patterns was characterized by
      scanning electron microscopy (SEM). Mineralization of the bioactive glass
      patterns was induced in vitro by soaking the samples in SBF over different time
      points up to 7 days. The confined apatite deposition in the patterned regions
      with diameters of 50 MUm was confirmed by Fourier-transformed infrared
      spectroscopy (FTIR), energy-dispersive X-ray (EDX) analysis, and SEM. In vitro
      tests confirmed the preferential attachment and proliferation of L929 cells to
      the areas printed with BG-NPs of the membranes. This approach permits one to
      spatially control the properties of biomaterials at the microlevel and could be
      potentially used in guided tissue regeneration for skin, vascular, articular, and
      bone tissue engineering and in cellular cocultures or to develop substrates able
      to confine cells in regions with controlled geometry at the cell's length scale.

PMID- 22480213
TI  - Interplay between local versus soluble transforming growth factor-beta and fibrin
      scaffolds: role of cells and impact on human mesenchymal stem cell
      chondrogenesis.
AB  - Structural extracellular matrix molecules gain increasing attention as scaffolds
      for cartilage tissue engineering owing to their natural role as a growth factor
      repository. We recently observed that a collagen-type I/III (Col-I/III) matrix,
      human recombinant transforming growth factor-beta (TGF-beta) protein, and fibrin
      hydrogel (FG) combined to a biphasic construct provided sufficient long-term TGF
      beta support to drive in vitro chondrogenesis of human mesenchymal stem cells
      (hMSC). Here we ask whether FG and Col-I/III can both retain TGF-beta, describe
      the influence of cell seeding on TGF-beta release, and compare the molecular path
      of hMSC chondrogenic differentiation under soluble versus local TGF-beta supply.
      Release of growth factor from scaffolds augmented with increasing amounts of TGF
      beta was analyzed over 7 days and chondrogenesis was assessed over 42 days. Low
      TGF-beta release rates from Col-I/III as opposed to higher release from FG
      indicated that both molecules retained TGF-beta, with Col-I/III being the
      superior storage component. Cell seeding enhanced TGF-beta retention in FG by
      about threefold and almost stopped release beyond 24 h. TGF-beta remained
      bioactive and supported MSC chondrogenesis without impairing the amount of
      proteoglycan and collagen-type II deposition per cell and per construct compared
      to standard scaffold-free MSC pellets supplied with soluble TGF-beta. Local TGF
      beta, however, mediated lower cell content, less collagen-type X relative to
      collagen-type II deposition and no matrix metalloproteinase-13 up-regulation. In
      conclusion, cells quickly halted release of local TGF-beta from FG, turning FG
      and Col-I/III into attractive TGF-beta repositories capable to drive full hMSC
      chondrogenesis, but via a modulated differentiation pathway. Since only part of
      the changes was reproduced by transient soluble TGF-beta supply, release kinetics
      alone could not explain the molecular differences, suggesting that local TGF-beta
      acts distinct from its soluble counterpart.

PMID- 22480214
TI  - Application of dearomatization strategy on the synthesis of furoquinolinone and
      angelicin derivatives.
AB  - The oxidative dearomatization of 3-(3-alkynyl-4-hydroxyphenyl)propanoic acid is
      combined with a cascade transition-metal catalyzed
      cyclization/addition/aromatization/lactamization sequence, which provides a novel
      approach to prepare furoquinolinone and angelicin derivatives in a convergent and
      efficient manner.

PMID- 22480215
TI  - Hepatoprotective effects and HSV-1 activity of the hydroethanolic extract of
      Cecropia glaziovii (embauba-vermelha) against acyclovir-resistant strain.
AB  - CONTEXT: Cecropia glaziovii Snethl. (Cecropiaceae), commonly known as "embauba
      vermelha", is widely distributed throughout Latin America and has been reported
      in Brazilian folk medicine to treat cough, asthma, high blood pressure and
      inflammation. OBJECTIVE: Investigate the hepatoprotective properties of crude
      hydroethanolic extract of C. glaziovii as well as its in vitro antioxidant and
      antiviral (HSV-1 acyclovir resistant strain) activities. MATERIALS AND METHODS:
      The hepatoprotective effect, the antioxidant properties and antiviral activity of
      crude hydroethanol extract (RCE40) from C. glaziovii leaves were evaluated by
      carbon-tetrachloride (CCl(4))-induced hepatotoxicity, by TBARS (thiobarbituric
      acid reactive species) and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide] assays, respectively. RESULTS: The RCE40 extract (20 mg/kg)
      inhibited lipid peroxidation on liver in post injury treatment and decreased
      serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST). In addition, in this protocol the RCE40 (20 mg/kg) enhanced the activity
      of hepatic enzymes (SOD/CAT) which are involved in combating reactive oxygen
      species (ROS), suggesting that it possesses the capacity to attenuate the CCl(4)
      induced liver damage. Moreover the RCE40 (20 mg/kg) inhibited TBARS formation
      induced by several different inductors of oxidative stress showing significant
      antioxidant activity, including physiologically relevant concentration, as low as
      2 ug/mL. Concerning antiviral activity, the RCE40 was effective against herpes
      simplex virus type 1 replication (29R acyclovir resistant strain) with EC(50) =
      40 ug/mL and selective index (SI) = 50. DISCUSSION AND CONCLUSION: These results
      indicate that C. glaziovii could be a good source of antioxidant and anti-HSV-1
      lead compounds.

PMID- 22480216
TI  - Low expression of stathmin in tumor predicts high response to neoadjuvant
      chemotherapy with docetaxel-containing regimens in locally advanced breast
      cancer.
AB  - AIMS: We performed this retrospective study to evaluate the value of
      clinicopathological factors and a novel molecular marker stathmin in predicting
      treatment response to neoadjuvant chemotherapy (NCT) with docetaxel-containing
      regimens in patients with locally advanced breast cancer. METHODS: Fifty-four
      consecutive locally advanced patients receiving docetaxel-containing NCT between
      January 2006 and July 2010 in Zhejiang Cancer Hospital were included. The
      expression levels of estrogen receptor (ER), progesterone receptor (PgR),
      epidermal growth factor receptor-2 (HER-2), and p53 were detected by
      immunohistochemistry, while expression of stathmin mRNA was measured by Quanti
      Gene assay. RESULTS: The overall clinical objective response (cOR) rate was 75.9%
      (41/54) in breast. A total of 34 patients (63.0%) experienced pathological OR
      (pOR), with pathological complete remission (pCR) rate of 20.4% (11/54) in breast
      and 16.7% (9/54) in both breast and axilla. In univariate analysis, there were
      associations of pOR in both breast and axilla with age (p=0.054), ER status
      (p=0.059), subtypes (p=0.062), p53 (p=0.030), and stathmin expression (three
      terciles) (p=0.039). Mean expression of stathmin in pOR group was 0.410, compared
      with that in no response group of 0.556 (p=0.051 by Student's t-test). Similarly,
      a lower expression of stathmin might represent a higher pCR rate (p=0.061).
      Moreover, the LOWESS smoothing plot showed the same trend, that is, that tumor
      with a lower level of stathmin expression had a higher probability of response to
      docetaxel-containing NCT. After multivariate adjustment, both ER and stathmin
      remained significant with hazard ratio of 4.58 (95% CI: 1.11-18.94, p=0.036) and
      2.94 (95% CI: 1.26-6.86, p=0.012), respectively. CONCLUSIONS: In conclusion, ER
      and stathmin were independent predictive factors for NCT with docetaxel
      containing regimens.

PMID- 22480217
TI  - Parapharyngeal space hemangiopericytoma treated with surgery and postoperative
      radiation--a case report.
AB  - Hemangiopericytoma (HPC) is a rare tumor of uncertain malignant potential arising
      from mesenchymal cells with pericytic differentiation. It accounts for 3-5% of
      soft tissue sarcomas and 1% of vascular tumors. It usually presents in 5th to 6th
      decade of life. Most common sites are limbs, pelvis and head and neck. About 20%
      of all hemangiopericytomas are seen in head and neck, mostly in adults. Usually
      it presents in orbit, nasal cavity, oral cavity, jaw, parotid gland,
      parapharyngeal space, masticator space and jugular foramen. Long term follow up
      is important because of imprecise nature of the histological criteria for
      prediction of biologic behavior.We report herein a case of HPC in 66-year-old
      man, who presented in our department with headache, nasal obstruction and
      dysphagia. A neck computer tomography scan and magnetic resonance imaging showed
      a large left parapharyngeal mass bulging into nasopharynx and oropharynx with
      extension to pharyngeal mucosal surface and causing narrowing of airways and
      total obstruction of left posterior nostril. Angiography showed a highly vascular
      neoplasm. Initially he was managed as a case of schwannoma and embolization was
      done but with no response. An attempt to do complete surgical resection was made,
      but due to its critical position, it was not possible. During surgery, highly
      vascularised tumor was found. The histopathologic examination revealed a vascular
      tumor consistent with hemangiopericytoma G-II. The patient had normal
      postoperative course of healing and was given adjuvant radiation. He is on
      regular follow up without signs of recurrence or metastases.In summary,
      parapharyngeal space is a rare site of presentation for hemangiopericytoma which
      is highly vascular tumor, requiring extensive work up including magnetic
      resonance imaging, computed tomography scan and angiography. Complete surgical
      excision should be attempted. Postoperative radiation is indicated in cases of
      incomplete resection.

PMID- 22480218
TI  - Energy-resolved collision-induced dissociation of peroxyformate anion: enthalpies
      of formation of peroxyformic acid and peroxyformyl radical.
AB  - We measure the oxygen-oxygen bond dissociation energy of the peroxyformate anion
      (HCO(3)(-)) using energy-resolved collision-induced dissociation with a guided
      ion beam tandem mass spectrometer. The analysis of the dissociation process from
      HCO(3)(-) ((1)A') to HCO(2)(-) ((1)A(2)) + O((3)P) requires consideration of the
      singlet-triplet crossing along the reaction path and of the competing OH(-) and
      O(2)H(-) product channels. The measured oxygen-oxygen bond dissociation energy is
      D(0)(HCO(2)(-)-O) = 1.30 +/- 0.13 eV (126 +/- 12 kJ/mol). This threshold energy
      measurement is used in thermochemical cycles to derive the enthalpies of
      formation for peroxyformic acid, Delta(f)H(0)(HCO(3)H) = -287 +/- 19 kJ/mol, and
      peroxyformyl radical, Delta(f)H(0)(HCO(3)(*)) = -98 +/- 12 kJ/mol. These values
      are in good agreement with computational energies.

PMID- 22480219
TI  - Superhydrophobic alkanethiol-coated microsubmarines for effective removal of oil.
AB  - We demonstrate the use of artificial nanomachines for effective interaction,
      capture, transport, and removal of oil droplets. The simple nanomachine-enabled
      oil collection method is based on modifying microtube engines with a
      superhydrophobic layer able to adsorb oil by means of its strong adhesion to a
      long chain of self-assembled monolayers (SAMs) of alkanethiols created on the
      rough gold outer surface of the device. The resultant SAM-coated Au/Ni/PEDOT/Pt
      microsubmarine displays continuous interaction with large oil droplets and is
      capable of loading and transporting multiple small oil droplets. The influence of
      the alkanethiol chain length, polarity, and head functional group and hence of
      the surface hydrophobicity upon the oil-nanomotor interaction and the propulsion
      is examined. No such oil-motor interactions were observed in control experiments
      involving both unmodified microengines and microengines coated with SAM layers
      containing a polar terminal group. These results demonstrate that such SAM
      Au/Ni/PEDOT/Pt micromachines can be useful for a facile, rapid, and efficient
      collection of oils in water samples, which can be potentially exploited for other
      water-oil separation systems. The integration of oil-sorption properties into
      self-propelled microengines holds great promise for the remediation of oil
      contaminated water samples and for the isolation of other hydrophobic targets,
      such as drugs.

PMID- 22480221
TI  - Stable two-coordinate, open-shell (d1-d9) transition metal complexes.

PMID- 22480220
TI  - Magic-angle-spinning NMR of the drug resistant S31N M2 proton transporter from
      influenza A.
AB  - We report chemical shift assignments of the drug-resistant S31N mutant of M2(18
      60) determined using 3D magic-angle-spinning (MAS) NMR spectra acquired with a
      (15)N-(13)C ZF-TEDOR transfer followed by (13)C-(13)C mixing by RFDR. The MAS
      spectra reveal two sets of resonances, indicating that the tetramer assembles as
      a dimer of dimers, similar to the wild-type channel. Helicies from the two sets
      of chemical shifts are shown to be in close proximity at residue H37, and the
      assignments reveal a difference in the helix torsion angles, as predicted by
      TALOS+, for the key resistance residue N31. In contrast to wild-type M2(18-60),
      chemical shift changes are minimal upon addition of the inhibitor rimantadine,
      suggesting that the drug does not bind to S31N M2.

PMID- 22480222
TI  - Clinical requests for molecular tests: the 3-step evidence check.
AB  - Laboratory tests performed by molecular methods are increasing in volume and
      complexity at an unprecedented rate. Molecular tests have a broad set of
      applications, and most recently have been advocated as the mechanism by which
      providers can further tailor treatments to the individual patient. As the
      momentum behind molecular testing continues to increase, pathology practices may
      find themselves unprepared for the new wave of molecular medicine. This special
      article has been developed in an effort to provide pathologists who have limited
      molecular training with a simple and quick algorithm for determining whether a
      requested molecular test is appropriate for a patient. Additional recommendations
      for a more intensive and proactive review and management of molecular requests
      also are included. The principles discussed can easily be applied to requests for
      any test, including those not using molecular methods, which would be sent to an
      outside reference laboratory. This special article was developed from a Webinar
      for the College of American Pathologists targeting education for pathologists
      about the transformation of pathology practice in the new molecular and digital
      age.

PMID- 22480223
TI  - Correlation between histologic assessment and fluorescence in situ hybridization
      using MelanoSITE in evaluation of histologically ambiguous melanocytic lesions.
AB  - CONTEXT: The 4-probe, multicolor, fluorescence in situ hybridization (FISH) panel
      targeting chromosomes 6 and 11 has shown promising sensitivity and specificity in
      distinguishing between benign nevi and malignant melanoma. Only a few studies
      have assessed the potential utility of FISH in classification of histologically
      ambiguous melanocytic lesions. In the United States, this assay is exclusively
      licensed to NeoGenomics Laboratories (Irvine, California), which provides the
      technical component and has developed an innovative service (MelanoSITE) allowing
      pathologists to interpret FISH results using a dedicated Web portal. Thus far,
      use of MelanoSITE as a diagnostic adjunct in the diagnosis of melanocytic lesions
      has not, to our knowledge, been reported in the literature. OBJECTIVE: To analyze
      1.5 years of experience with the MelanoSITE melanoma FISH assay in the evaluation
      of histologically ambiguous lesions in the context of second opinion and routine
      dermatopathology practice. DESIGN: A prospective histologic/FISH correlation
      study of 140 cases. RESULTS: Twenty-seven percent of abnormal FISH results were
      false-positive results because of tetraploidy. After correcting for known false
      positive results, all lesions considered atypical nevi showed normal FISH
      signals. Abnormal FISH signals were reported in 30% of lesions considered
      histologically borderline and in 48% of lesions in which a diagnosis of melanoma
      was favored. CONCLUSIONS: Four-probe, multicolor FISH results for melanoma
      correlate with the microscopic assessments of histologically ambiguous lesions.
      Pathologists using MelanoSITE must be aware of the high rate of false-positive
      results from tetraploidy.

PMID- 22480224
TI  - Recency of Pap testing and future testing plans among women aged 18-64: analysis
      of the 2007 Health Information National Trends Survey.
AB  - BACKGROUND: Cervical cancer incidence has declined as a result of Papanicolaou
      (Pap) test use. Current guidelines recommend increasing screening intervals for
      women of average risk. The objective of this study is to examine current
      screening intervals, factors associated with recency of Pap testing, and future
      testing plans. METHODS: We analyzed data from 2915 female respondents, aged 18
      64, using the 2007 Health Information National Trends Survey (HINTS), a biennial
      national survey of access and use of cancer information in the United States. We
      divided time since last Pap test into <=1 year (n=1960), >1 to <=3 years (n=512),
      >3 years/never had Pap test (n=443). We performed univariate analyses and
      multivariate logistic regression, using proportional odds model with cumulative
      logit link. RESULTS: Sixty-five percent of women had their most recent Pap test
      within 1 year. Most expected to be screened again within 1 year (81%). This
      expectation was highest among women who were tested within the previous year
      (90.9%). Having had a test within 1 year was positively associated with age
      groups 31-45 vs. 46-64 years; with being non-Hispanic black vs. non-Hispanic
      white; with being a college graduate vs. having less education; with being
      married, divorced, or separated vs. widowed; with having at least one visit to a
      healthcare provider in the past year; and with being aware of the human
      papillomavirus (HPV). CONCLUSIONS: Most women currently are tested and anticipate
      future testing at annual intervals. To implement guidelines, increased
      communication and systematic or policy changes may be needed to reduce
      overtesting.

PMID- 22480230
TI  - Substance abuse prevalence and its relation to scholastic achievement and sport
      factors: an analysis among adolescents of the Herzegovina-Neretva Canton in
      Bosnia and Herzegovina.
AB  - BACKGROUND: Substance abuse among adolescents is a major public health and social
      problem. However, studies rarely investigate the relationships between substance
      abuse, educational achievement and sport factors. Substance abuse is an even more
      significant problem in societies that have experienced trauma, such as Bosnia and
      Herzegovina, which have had recent wars. The aims of this study were to
      investigate substance abuse among adolescents in Bosnia and Herzegovina and to
      study the potential gender-specific relationships between a) sport factors
      (physical activity/exercise/athletic participation) and substance abuse and b)
      scholastic achievement and substance abuse. METHODS: Our sample consisted of
      1,032 adolescents who were 17 to 18 years old (435 boys and 597 girls) and who
      were in the final grade of high school. These subjects were randomly selected
      from the territory of Herzegovina-Neretva Canton of Bosnia and Herzegovina.
      Retrospective testing was performed using an extensive self-administered
      questionnaire. The questionnaire included questions involving topics such as
      sociodemographic variables, scholastic variables, sport factors, and substance
      abuse data (smoking habits, drugs consumption and alcohol consumption using the
      AUDIT questionnaire). Descriptive statistics, frequencies, analyses of the
      differences and correlational analyses were performed. RESULTS: Our results found
      that greater than one-third of the boys and one-fourth of the girls were daily
      smokers, and almost half of the boys and one-fifth of the girls practiced harmful
      drinking; other drugs (i.e. heroin, cocaine, amphetamines, etc.) were rarely
      consumed. Boys dominated in sport factors, whereas girls were more successful in
      scholastic achievement. Approximately 23% of the boys and 6% of the girls
      reported that they practiced harmful drinking and smoked simultaneously.
      Educational failure, which was defined as having one or more negative grades at
      the end of the last two school years, was identified in 20% of the boys and 9% of
      the girls. In both genders, substance abuse was negatively correlated with
      educational achievement, and half of those students who failed educationally
      reported daily smoking. Among the girls who experienced education failure, 33%
      were smokers, and 22% practiced harmful drinking. Sport factors were weakly
      correlated with substance abuse in boys; thus, we could not support the
      hypothesis that sports are a protective factor against substance abuse among male
      adolescents. In girls, participation in team sports was related with a higher
      incidence of smoking, but there was no evidence of sport factors having an
      influence on the consumption of alcohol. CONCLUSION: In this study, the incidence
      of smoking and the consumption of alcohol were alarmingly high. These findings
      demonstrate the need for intervention programs to address these issues. These
      problems are particularly important, considering that substance abuse has a
      negative impact on educational achievement among boys and girls, and sport
      factors have not been found to be protective factors against substance abuse.

PMID- 22480231
TI  - Treatment of adult soft tissue sarcoma: old concepts, new insights, and potential
      for drug discovery.
AB  - Soft tissue sarcomas are a heterogeneous group of mesenchymal tumors that vary in
      their behavior as well as treatment. Certain histologic subtypes predict for
      response to particular chemotherapy drugs, while molecular genetics not only
      increasingly aid in the diagnosis but also has an emerging role in the
      identification of potential targets for drug therapy. Herein we review the
      varying soft tissue sarcoma subtypes, their staging, and management. Furthermore,
      improvement in the understanding of novel mechanisms involved in soft tissue
      sarcomas lends insight into the compelling role of the use of newer agents with
      promising results that are discussed.

PMID- 22480225
TI  - Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic
      approaches to target SPARC-induced glioma cell survival.
AB  - BACKGROUND: The current treatment regimen for glioma patients is surgery,
      followed by radiation therapy plus temozolomide (TMZ), followed by 6 months of
      adjuvant TMZ. Despite this aggressive treatment regimen, the overall survival of
      all surgically treated GBM patients remains dismal, and additional or different
      therapies are required. Depending on the cancer type, SPARC has been proposed
      both as a therapeutic target and as a therapeutic agent. In glioma, SPARC
      promotes invasion via upregulation of the p38 MAPK/MAPKAPK2/HSP27 signaling
      pathway, and promotes tumor cell survival by upregulating pAKT. As HSP27 and AKT
      interact to regulate the activity of each other, we determined whether inhibition
      of HSP27 was better than targeting SPARC as a therapeutic approach to inhibit
      both SPARC-induced glioma cell invasion and survival. RESULTS: Our studies found
      the following. 1) SPARC increases the expression of tumor cell pro-survival and
      pro-death protein signaling in balance, and, as a net result, tumor cell survival
      remains unchanged. 2) Suppressing SPARC increases tumor cell survival, indicating
      it is not a good therapeutic target. 3) Suppressing HSP27 decreases tumor cell
      survival in all gliomas, but is more effective in SPARC-expressing tumor cells
      due to the removal of HSP27 inhibition of SPARC-induced pro-apoptotic signaling.
      4) Suppressing total AKT1/2 paradoxically enhanced tumor cell survival,
      indicating that AKT1 or 2 are poor therapeutic targets. 5) However, inhibiting
      pAKT suppresses tumor cell survival. 6) Inhibiting both HSP27 and pAKT
      synergistically decreases tumor cell survival. 7) There appears to be a complex
      feedback system between SPARC, HSP27, and AKT. 8) This interaction is likely
      influenced by PTEN status. With respect to chemosensitization, we found the
      following. 1) SPARC enhances pro-apoptotic signaling in cells exposed to TMZ. 2)
      Despite this enhanced signaling, SPARC protects cells against TMZ. 3) This
      protection can be reduced by inhibiting pAKT. 4) Combined inhibition of HSP27 and
      pAKT is more effective than TMZ treatment alone. CONCLUSIONS: We conclude that
      inhibition of HSP27 alone, or in combination with pAKT inhibitor IV, may be an
      effective therapeutic approach to inhibit SPARC-induced glioma cell invasion and
      survival in SPARC-positive/PTEN-wildtype and SPARC-positive/PTEN-null tumors,
      respectively.

PMID- 22480232
TI  - Cystinuria: an inborn cause of urolithiasis.
AB  - Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a
      defective cystine metabolism resulting in the formation of cystine stones. Among
      the heterogeneous group of kidney stone diseases, cystinuria is the only disorder
      which is exclusively caused by gene mutations. So far, two genes responsible for
      cystinuria have been identified: SLC3A1 (chromosome 2p21) encodes the heavy
      subunit rBAT of a renal b(0,+) transporter while SLC7A9 (chromosome 19q12)
      encodes its interacting light subunit b(0,+)AT. Mutations in SLC3A1 are generally
      associated with an autosomal-recessive mode of inheritance whereas SLC7A9
      variants result in a broad clinical variability even within the same family. The
      detection rate for mutations in these genes is larger than 85%, but it is
      influenced by the ethnic origin of a patient and the pathophysiological
      significance of the mutations. In addition to isolated cystinuria, patients
      suffering from the hypotonia-cystinuria syndrome have been reported carrying
      deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive
      molecular screening studies in large cohort of patients a broad spectrum of
      mutations could be identified, several of these variants were functionally
      analysed and thereby allowed insights in the pathology of the disease as well as
      in the renal trafficking of cystine and the dibasic amino acids. In our review we
      will summarize the current knowledge on the physiological and the genetic basis
      of cystinuria as an inborn cause of kidney stones, and the application of this
      knowledge in genetic testing strategies.

PMID- 22480233
TI  - Low molecular weight poly(lactic acid) microparticles for controlled release of
      the herbicide metazachlor: preparation, morphology, and release kinetics.
AB  - The preemergence chloroacetamide herbicide metazachlor was encapsulated in
      biodegradable low molecular weight poly(lactic acid) micro- and
      submicroparticles, and its release to the water environment was investigated.
      Three series of particles, S, M, and L, varying in their size (from 0.6 to 8 MUm)
      and with various initial amounts of the active agent (5%, 10%, 20%, 30% w/w) were
      prepared by the oil-in-water solvent evaporation technique with gelatin as
      biodegradable surfactant. The encapsulation efficiencies reached were about 60%
      and appeared to be lower for smaller particles. Generally, it was found that the
      rate of herbicide release decreased with increasing size of particles. After 30
      days the portions of the herbicide released for its highest loading (30% w/w)
      were 92%, 56%, and 34% for about 0.6, 0.8, and 8 MUm particles, respectively. The
      release rates were also lower for lower herbicide loadings. Metazachlor release
      from larger particles tended to be a diffusion-controlled process, while for
      smaller particles the kinetics was strongly influenced by an initial burst
      release.

PMID- 22480234
TI  - Gene expression in Atlantic salmon skin in response to infection with the
      parasitic copepod Lepeophtheirus salmonis, cortisol implant, and their
      combination.
AB  - BACKGROUND: The salmon louse is an ectoparasitic copepod that causes major
      economic losses in the aquaculture industry of Atlantic salmon. This host
      displays a high level of susceptibility to lice which can be accounted for by
      several factors including stress. In addition, the parasite itself acts as a
      potent stressor of the host, and outcomes of infection can depend on biotic and
      abiotic factors that stimulate production of cortisol. Consequently, examination
      of responses to infection with this parasite, in addition to stress hormone
      regulation in Atlantic salmon, is vital for better understanding of the host
      pathogen interaction. RESULTS: Atlantic salmon post smolts were organised into
      four experimental groups: lice + cortisol, lice + placebo, no lice + cortisol, no
      lice + placebo. Infection levels were equal in both treatments upon termination
      of the experiment. Gene expression changes in skin were assessed with 21 k
      oligonucleotide microarray and qPCR at the chalimus stage 18 days post infection
      at 9 degrees C. The transcriptomic effects of hormone treatment were
      significantly greater than lice-infection induced changes. Cortisol stimulated
      expression of genes involved in metabolism of steroids and amino acids,
      chaperones, responses to oxidative stress and eicosanoid metabolism and
      suppressed genes related to antigen presentation, B and T cells, antiviral and
      inflammatory responses. Cortisol and lice equally down-regulated a large panel of
      motor proteins that can be important for wound contraction. Cortisol also
      suppressed multiple genes involved in wound healing, parts of which were
      activated by the parasite. Down-regulation of collagens and other structural
      proteins was in parallel with the induction of proteinases that degrade
      extracellular matrix (MMP9 and MMP13). Cortisol reduced expression of genes
      encoding proteins involved in formation of various tissue structures, regulators
      of cell differentiation and growth factors. CONCLUSIONS: These results suggest
      that cortisol-induced stress does not affect the level of infection of Atlantic
      salmon with the parasite, however, it may retard repair of skin. The cortisol
      induced changes are in close concordance with the existing concept of wound
      healing cascade.

PMID- 22480235
TI  - Modulating the rigidity and mineralization of collagen gels using poly(lactic-co
      glycolic acid) microparticles.
AB  - Extensive efforts have been made to prepare osteoconductive collagen gels for the
      regeneration of normal bone and the pathological examination of diseased bone;
      however, collagen gels are often plagued by limited controllability of their
      rigidity and mineral deposition. This study reports a simple but efficient
      strategy that tunes the mechanical properties of, and apatite formation in,
      collagen gels by incorporating hydrolyzable poly(lactic-co-glycolic acid) (PLGA)
      microparticles within the gels. The PLGA microparticles are associated with the
      collagen fibrils and increased both the gel's elasticity and rigidity while
      minimally influencing its permeability. As compared with pure collagen gels, the
      PLGA microparticle-filled collagen gels, termed PLGA-Col hydrogels, significantly
      enhanced the deposition of apatite-like minerals within the gels when incubated
      in simulated body fluid or encapsulated with mesenchymal stem cells (MSCs)
      undergoing osteogenic differentiation. Finally, PLGA-Col hydrogels mineralized by
      differentiated MSCs led to an enhanced formation of bone-like tissues within the
      hydrogels. Overall, the PLGA-Col hydrogel system developed in this study will
      serve to improve the quality of osteoconductive matrices for both fundamental and
      clinical studies that are relevant to bone repair, regeneration, and
      pathogenesis.

PMID- 22480236
TI  - Evidence for metabolic cleavage of a PEGylated protein in vivo using multiple
      analytical methodologies.
AB  - PEGylation of therapeutic proteins is commonly used to extend half-lives and to
      reduce immunogenicity. However, reports of antibodies toward PEGylated proteins
      and of poly(ethylene glycol) (PEG) accumulation suggest that efficacy and safety
      concerns may arise. To understand the relationship among the pharmacology,
      immunogenicity, and toxicology of PEGylated proteins, we require knowledge of the
      disposition and metabolic fate of both the drug and the polymer moieties. The
      analysis of PEG by standard spectrophotometric or mass spectrometric techniques
      is problematic. Consequently, we have examined and compared two independent
      analytical approaches, based on gel electrophoresis and nuclear magnetic
      resonance (NMR) spectroscopy, to determine the biological fate of a model
      PEGylated protein, (40K)PEG-insulin, within a rat model. Both immunoblotting with
      an antibody to PEG and NMR analyses (LOD 0.5 MUg/mL for both assays) indicated
      that the PEG moiety remained detectable for several weeks in both serum and urine
      following intravenous administration of (40K)PEG-insulin (4 mg/kg). In contrast,
      Western blotting with anti-insulin IgG indicated that the terminal half-life of
      the insulin moiety was far shorter than that of the PEG, providing clear evidence
      of conjugate cleavage. The application of combined analytical techniques in this
      way thus allows simultaneous independent monitoring of both protein and polymer
      elements of a PEGylated molecule. These methodologies also provide direct
      evidence for cleavage and definition of the chemical species present in
      biological fluids which may have toxicological consequences due to unconjugated
      PEG accumulation or immunogenic recognition of the uncoupled protein.

PMID- 22480237
TI  - Ligand effects on the stereochemical outcome of Suzuki-Miyaura couplings.
AB  - The ligands associated with various Pd catalysts play a crucial role in
      determining the stereochemistry of cross-couplings between boronic acids and Z
      alkenyl halides. A ligand on palladium has been found that leads to the desired
      products under mild conditions and in high yields that, in most cases, retain
      their Z-olefin geometry.

PMID- 22480238
TI  - Application of NMR metabolomics to search for human disease biomarkers.
AB  - Since antiquity, humans have used body fluids like saliva, urine and sweat for
      the diagnosis of diseases. The amount, color and smell of body fluids are still
      used in many traditional medical practices to evaluate an illness and make a
      diagnosis. The development and application of analytical methods for the detailed
      analysis of body fluids has led to the discovery of numerous disease biomarkers.
      Recently, mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR),
      and multivariate statistical techniques have been incorporated into a
      multidisciplinary approach to profile changes in small molecules associated with
      the onset and progression of human diseases. The goal of these efforts is to
      identify metabolites that are uniquely correlated with a specific human disease
      in order to accurately diagnose and treat the malady. In this review we will
      discuss recent developments in sample preparation, experimental techniques, the
      identification and quantification of metabolites, and the chemometric tools used
      to search for biomarkers of human diseases using NMR.

PMID- 22480239
TI  - Fabrication of functional waterborne polyurethane/montmorillonite composites by
      click chemistry method.
AB  - "Click" chemistry method was used to fabricate novel waterborne polyurethane
      (WPU)/montmorillonite (MMT) composites based on alkyne-containing WPU and azide
      modified montmorillonite. The morphology of these composites was characterized by
      x-ray diffractometer, scanning electron microscope. The mechanical properties,
      thermal stability, and flame resistance of the composites were investigated by
      tensile, thermogravimetry and cone calorimetric experiments, etc. The
      experimental results show that the tensile strength, water resistance and flame
      retardancy of the WPU/MMT composites have been reinforced efficiently owing to
      the linking of MMT by click reaction.

PMID- 22480240
TI  - Lanthanide-doped inorganic nanocrystals as luminescent biolabels.
AB  - Trivalent lanthanide ions (Ln(3+)) doped inorganic nanocrystals (NCs) have
      currently attracted reviving interest and come to the forefront in nanophotonics
      owing to their potential applications in diverse fields such as luminescent
      biodetection and bioimaging. As an alternative to conventional biolabels, Ln(3+)
      doped NCs show superior features including large stokes shift, multicolor fine
      tuning, narrow emission band widths, high photostability, and low toxicity.
      Particularly, the long-lived luminescence and distinct upconversion (UC) of
      Ln(3+)-doped NCs are desirable for various bioapplications. The long-lived
      luminescence of Ln(3+) combined with time-resolved technique can efficiently
      suppress the interference from short-lived background, resulting in a high signal
      to-noise ratio (S/N) and background-free measurements. Near-infrared excited UC
      emissions of Ln(3+) can bring no autofluorescence and no photodamage to cells or
      tissues, and thus UC NCs have been regarded as one of the most useful in vivo
      optical contrast agents. In this review, we outline the most recent development
      of Ln(3+)-doped NCs as biolabels from the controlled synthesis and surface
      functionalization of NCs to their bioapplications in heterogeneous and
      homogeneous biodetection as well as in vitro and in vivo bioimaging.

PMID- 22480241
TI  - Exciton band structure in bacterial peripheral light-harvesting complexes.
AB  - The variability of the exciton spectra of bacteriochlorophyll molecules in light
      harvesting (LH) complexes of photosynthetic bacteria ensures the excitation
      energy funneling trend toward the reaction center. The decisive shift of the
      energies is achieved due to exciton spectra formation caused by the resonance
      interaction between the pigments. The possibility to resolve the upper Davydov
      sub-band corresponding to the B850 ring and, thus, to estimate the exciton
      bandwidth by analyzing the temperature dependence of the steady-state absorption
      spectra of the LH2 complexes is demonstrated. For this purpose a self-modeling
      curve resolution approach was applied for  analysis of the temperature dependence
      of the absorption spectra of LH2 complexes from the photosynthetic bacteria
      Rhodobacter (Rba.) sphaeroides and Rhodoblastus (Rbl.) acidophilus. Estimations
      of the intradimer resonance interaction values as follows directly from obtained
      estimations of the exciton bandwidths at room temperature give 385 and 397 cm(-1)
      for the LH2 complexes from the photosynthetic bacteria Rba. sphaeroides and Rhl.
      acidophilus, respectively. At 4 K the corresponding couplings are slightly higher
      (391 and 435 cm(-1), respectively). The retained exciton bandwidth at
      physiological conditions supports the decisive role of the exciton coherence
      determining  light absorption in bacterial light-harvesting antenna complexes.

PMID- 22480242
TI  - Azetidine iminosugars from the cyclization of 3,5-di-O-triflates of alpha
      furanosides and of 2,4-di-O-triflates of beta-pyranosides derived from glucose.
AB  - Primary amines with either 3,5-di-O-ditriflates of alpha-furanosides or 2,4-di-O
      triflates of beta-pyranosides form bicyclic azetidines in high yield.

PMID- 22480243
TI  - Occurrence, biogenesis, and synthesis of biologically active carbazole alkaloids.

PMID- 22480244
TI  - Advection dominated transport of polycyclic aromatic hydrocarbons in amended
      sediment caps.
AB  - Typical sand caps used for sediment remediation have little sorption capacity to
      retard the migration of hydrophobic contaminants such as PAHs that can be
      mobilized by significant groundwater flow. Laboratory column experiments were
      performed using contaminated sediments and capping materials from a creosote
      contaminated USEPA Superfund site. Azoic laboratory column experiments
      demonstrated rapid breakthrough of lower molecular weight PAHs when groundwater
      seepage was simulated through a column packed with coarse sand capping material.
      After eight pore volumes of flow, most PAHs measured showed at least 50% of
      initial source pore water concentrations at the surface of 65 cm capping
      material. PAH concentration in the cap solids was low and comparable to
      background levels typically seen in urban depositional sediment, but the pore
      water concentrations were high. Column experiments with a peat amendment delayed
      PAH breakthrough. The most dramatic result was observed for caps amended with
      activated carbon at a dose of 2% by dry weight. PAH concentrations in the pore
      water of the activated carbon amended caps were 3-4 orders of magnitude lower
      (0.04 +/- 0.02 MUg/L for pyrene) than concentrations in the pore water of the
      source sediments (26.2 +/- 5.6 MUg/L for pyrene) even after several hundred pore
      volumes of flow. Enhancing the sorption capacity of caps with activated carbon
      amendment even at a lower dose of 0.2% demonstrated a significant impact on
      contaminant retardation suggesting consideration of active capping for field
      sites prone to groundwater upwelling or where thin caps are desired to minimize
      change in bathymetry and impacts to aquatic habitats.

PMID- 22480245
TI  - In vitro and ex vivo anticholinesterase activities of Erythrina velutina leaf
      extracts.
AB  - CONTEXT: Erythrina velutina (EV) Willd (Fabaceae-Faboideae) is a medicinal tree
      that is commonly used in Brazil for the treatment of several central nervous
      system disorders. OBJECTIVE: The anticholinesterase activity of EV is described
      in this work. METHODS: Concentration-response curves (0-1.6 mg/mL) for EV leaf
      aqueous extract (AE) and alkaloid-rich extracts (AKEs) were performed in vitro.
      Cholinesterase inhibition was examined in mouse brains, as the cholinesterase
      source, and in pure acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE).
      Mice were treated with AE or AKE (100, 200, and 400 mg/kg, p.o.) and their brains
      were used for the measurement of cholinesterase activity (CA) ex vivo. RESULTS:
      CA was inhibited by AE (IC(50) = 0.57 [0.43-0.75] mg/mL) and AKE (IC(50) = 0.52
      [0.39-0.70] mg/mL) in brain homogenates in a concentration-dependent manner. The
      ex vivo experiments indicated that AE (400 mg/kg, p < 0.05, 32.2 +/- 3.9% of
      inhibition) and AKE (all doses: p < 0.05-p < 0.001, 29.6 +/- 3.2% as the maximum
      inhibition) significantly inhibited CA in the central nervous system after oral
      administration. AE and AKE inhibited AChE and BuChE activities in a concentration
      dependent manner (AE: IC(50AChE) = 0.56 [0.38-0.81] mg/mL, IC(50BuChE) = 2.95
      [1.51-5.76] mg/mL, AKE: IC(50AChE) = 0.87 [0.60-12.5] mg/mL, IC(50BuChE) = 2.67
      [0.87-8.11] mg/mL). DISCUSSION AND CONCLUSIONS: These data indicated that AE and
      AKE crossed the blood-brain barrier to inhibit CA in the brain. AE and AKE also
      exhibited a dual inhibitory action on acetyl- and BuChE.

PMID- 22480246
TI  - Rituximab-induced coagulopathy.

PMID- 22480247
TI  - The impact of a bariatric rehabilitation service on weight loss and psychological
      adjustment--study protocol.
AB  - BACKGROUND: Bariatric surgery is currently the most effective form of obesity
      management for those whose BMI is greater than 40 (or 35 with co morbidities). A
      minority of patients, however, either do not show the desired loss of excess
      weight or show weight regain by follow up. Research highlights some of the
      reasons for this variability, most of which centres on the absence of any
      psychological support with patients describing how although surgery fixes their
      body, psychological issues relating to dietary control, self esteem, coping and
      emotional eating remain neglected.The present study aims to evaluate the impact
      of a health psychology led bariatric rehabilitation service (BRS) on patient
      health outcomes. The bariatric rehabilitation service will provide information,
      support and mentoring pre and post surgery and will address psychological issues
      such as dietary control, self esteem, coping and emotional eating. The package
      reflects the rehabilitation services now common place for patients post heart
      attack and stroke which have been shown to improve patient health outcomes.
      METHODS/DESIGN: The study is a randomised control trial and patients will be
      allocated to receive either usual care or the bariatric rehabilitation service
      pre and post bariatric surgery. Follow up measures of weight loss and
      psychological issues will be taken at baseline (2 weeks preoperatively), 3, 6 and
      12 months postoperatively. The contents of the bariatric service and the follow
      up measures are based on previous pilot work and have been developed further by
      the research team working closely with two patient support groups (BOSPA &
      WLSinfo). This study will take place in St Richard's Hospital in Chichester in
      the UK. DISCUSSION: It is predicted that a bariatric rehabilitation service will
      improve weight loss following surgery and will also facilitate changes in other
      psychological variables such as quality of life, dietary control, self esteem,
      coping and emotional eating. This also has cost implications for the NHS and
      other healthcare providers as improved effectiveness of bariatric surgery reduces
      the health costs of obese patients in the longer term. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01264120.

PMID- 22480248
TI  - Vertical single-wall carbon nanotube forests as plasmonic heat pipes.
AB  - High thermal conductivity of carbon nanotubes (NTs) is attractive for the heat
      removal applications. However, the problem of efficient thermal coupling to the
      heater/cooler still needs to be resolved. We study near-field electromagnetic
      tunneling as a mechanism of heat transfer across the interface. We report
      interface thermal (Kapitza) conductance between a low-density vertical metallic
      single-wall NT forest and a quartz substrate on the order of 50 MW/Km(2) and
      explain it by strong electromagnetic interaction and near-field entanglement
      between the surface phonon-polaritons in the polar dielectric and the NT
      plasmons. We predict that the thickness of the NT film can be tweaked to the
      resonance wavelength of these entangled modes for performance optimization of
      nanocarbon thermal interconnects.

PMID- 22480250
TI  - Public health research support through the European structural funds in central
      and eastern Europe and the Mediterranean.
AB  - BACKGROUND: Public health research provides evidence for practice across fields
      including health care, health promotion and health surveillance. Levels of public
      health research vary markedly across European Union (EU) countries, and are
      lowest in the EU's new member states (in Central and Eastern Europe and the
      Mediterranean). However, these countries now receive most of the EU's Structural
      Funds, some of which are allocated to research. METHODS: STEPS, an EU-funded
      study, sought to assess support for public health research at national and
      European levels. To identify support through the Structural funds, STEPS drew
      information from country respondents and internet searches for all twelve EU new
      member states. RESULTS: The EU allocates annually around ?7 billion through the
      Structural Funds for member states' own use on research. These funds can cover
      infrastructure, academic employment, and direct research grants. The programmes
      emphasise links to business. Support for health research includes major projects
      in biosciences, but direct support for public health research was found in only
      three countries - Cyprus, Latvia and Lithuania. CONCLUSIONS: Public health
      research is not prioritised in the EU's Structural Funds programme in comparison
      with biomedicine. For the research dimension of the new European programme for
      Structural Funds 2014-2002, ministries of health should propose public health
      research to strengthen the evidence-base for European public health policy and
      practice.

PMID- 22480251
TI  - Coordination of phosphinoboranes R2PB(C6F5)2 to platinum: an alkene-type
      behavior.
AB  - The paucity of boron-containing heteroalkene complexes prompted us to explore the
      coordination of phosphinoboranes. The complexes
      {[R(2)PB(C(6)F(5))(2)]Pt(PPh(3))(2)} (R = Cy, t-Bu) were obtained by ethylene
      displacement. Spectroscopic and crystallographic data indicated symmetric side-on
      coordination of the phosphinoborane to Pt. Thorough analysis of the bonding
      situation by computational means revealed important similarities but also
      significant differences between the phosphinoborane and ethylene complexes.

PMID- 22480249
TI  - Inhibition of CD44 gene expression in human skin models, using self-delivery
      short interfering RNA administered by dissolvable microneedle arrays.
AB  - Treatment of skin disorders with short interfering RNA (siRNA)-based therapeutics
      requires the development of effective delivery methodologies that reach target
      cells in affected tissues. Successful delivery of functional siRNA to the
      epidermis requires (1) crossing the stratum corneum, (2) transfer across the
      keratinocyte membrane, followed by (3) incorporation into the RNA-induced
      silencing complex. We have previously demonstrated that treatment with
      microneedle arrays loaded with self-delivery siRNA (sd-siRNA) can achieve
      inhibition of reporter gene expression in a transgenic mouse model. Furthermore,
      treatment of human cultured epidermal equivalents with sd-siRNA resulted in
      inhibition of target gene expression. Here, we demonstrate inhibition of CD44, a
      gene that is uniformly expressed throughout the epidermis, by sd-siRNA both in
      vitro (cultured human epidermal skin equivalents) and in vivo (full-thickness
      human skin equivalents xenografted on immunocompromised mice). Treatment of human
      skin equivalents with CD44 sd-siRNA markedly decreased CD44 mRNA levels, which
      led to a reduction of the target protein as confirmed by immunodetection in
      epidermal equivalent sections with a CD44-specific antibody. Taken together,
      these results demonstrate that sd-siRNA, delivered by microneedle arrays, can
      reduce expression of a targeted endogenous gene in a human skin xenograft model.

PMID- 22480252
TI  - Focal brain trauma in the cryogenic lesion model in mice.
AB  - The method to induce unilateral cryogenic lesions was first described in 1958 by
      Klatzo. We describe here an adaptation of this model that allows reliable
      measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium
      chloride-staining and Evans blue extravasation in mice. A copper or aluminium
      cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen and placed
      on the exposed skull bone over the parietal cortex (coordinates from bregma: 1.5
      mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the
      tip and the parietal skull determine the extent of cryolesion. Due to an early
      damage of the blood brain barrier, the cryogenic cortical injury is characterized
      by vasogenic edema, marked brain swelling, and inflammation. The lesion grows
      during the first 24 hours, a process involving complex interactions between
      endothelial cells, immune cells, cerebral blood flow, and the intracranial
      pressure. These contribute substantially to the damage from the initial injury.
      The major advantage of the cryogenic lesion model is the circumscribed and highly
      reproducible lesion size and location.

PMID- 22480253
TI  - Definition and computation of intermolecular contact in liquids using additively
      weighted Voronoi tessellation.
AB  - We present a definition of intermolecular surface contact by applying weighted
      Voronoi tessellations to configurations of various organic liquids and water
      obtained from molecular dynamics simulations. This definition of surface contact
      is used to link the COSMO-RS model and molecular dynamics simulations. We
      demonstrate that additively weighted tessellation is the superior tessellation
      type to define intermolecular surface contact. Furthermore, we fit a set of
      weights for the elements C, H, O, N, F, and S for this tessellation type to
      obtain optimal agreement between the models. We use these radii to successfully
      predict contact statistics for compounds that were excluded from the fit and
      mixtures. The observed agreement between contact statistics from COSMO-RS and
      molecular dynamics simulations confirms the capability of the presented method to
      describe intermolecular contact. Furthermore, we observe that increasing polarity
      of the surfaces of the examined molecules leads to weaker agreement in the
      contact statistics. This is especially pronounced for pure water.

PMID- 22480254
TI  - Acute human glufosinate-containing herbicide poisoning.
AB  - BACKGROUND: Glufosinate-containing herbicides are commonly used worldwide. Data
      on acute human glufosinate poisoning however remain scarce. METHODS: We
      retrospectively reviewed the medical records of all glufosinate poisoned cases
      reported to the Taiwan National Poison Control Center and two medical centers in
      Taiwan from August 1993 through February 2010. Their demographic and clinical
      data were then analyzed to identify potential predictors of severe effects
      following acute glufosinate poisoning. RESULTS: One hundred and thirty-one
      patients, including 115 oral and 16 non-oral exposures, were eligible for final
      analysis. Among patients with oral exposure, 25 were asymptomatic, while the
      others developed gastrointestinal, neurological, cardiovascular, and/or
      respiratory manifestations. Seven patients (6.1%) died following deliberate
      glufosinate ingestion. The median dose of glufosinate ingestion was 30.4 grams
      (interquartile range 18.5-45.6 grams) in the severe/fatal group compared to 6.8
      grams (interquartile range 3.7-16.2 grams) in the non-severe group (p <0.001).
      Older age (>= 61 years; adjusted OR 4.9, 95% CI 1.3-17.9) and larger amount of
      glufosinate ingestion (>= 13.9 grams; adjusted OR 25.2, 95% CI 4.8-132.5) were
      positively associated with the development of severe toxicity, whereas ethanol
      consumption (adjusted OR 0.1, 95% CI <0.1-0.5) was inversely associated with the
      risk of severe toxicity. CONCLUSION: Although glufosinate is generally thought to
      be of low toxicity to humans, severe effects can occur and may be associated with
      older age, larger amount of ingestion and absence of concomitant ethanol
      consumption.

PMID- 22480256
TI  - Targeting intracellular and extracellular alpha-synuclein as a therapeutic
      strategy in Parkinson's disease and other synucleinopathies.
AB  - INTRODUCTION: alpha-Synuclein is a neuronal presynaptic protein that regulates
      neurotransmitter release. Genetic, neuropathological, biochemical and animal
      model data indicate that it plays a major role in Parkinson's disease and other
      neurodegenerative disorders, acting through a toxic gain of function. Although
      the mechanism of the toxic function of alpha-Synuclein is not yet certain, it may
      involve multiple intracellular targets of the aberrantly misfolded, aggregated
      protein. It is generally thought that specific soluble oligomeric alpha-Synuclein
      species are the offending toxic agents. The total amount of alpha-Synuclein is a
      significant factor that determines its toxicity. alpha-Synuclein can also be
      secreted and can thus affect neuronal and glial function. Propagation of alpha
      Synuclein pathology via neuron-to-neuron transmission and seeding may also
      contribute to Parkinson's disease pathogenesis. AREAS COVERED: Key mechanisms of
      deregulation of alpha-Synuclein that could be relevant to neurodegeneration, and
      could offer opportunities for therapeutic intervention. EXPERT OPINION:
      Counteracting intracellular and extracellular effects of alpha-Synuclein
      represents a valid therapeutic target in neurodegeneration. In particular,
      strategies that target alpha-Synuclein through limitation of its burden at the
      transcriptional and post-transcriptional level, inhibition of its aggregation or
      of aberrant phosphorylation states, immunization or attenuation of its secretion
      and propagation may be therapeutic options.

PMID- 22480257
TI  - VESPA: software to facilitate genomic annotation of prokaryotic organisms through
      integration of proteomic and transcriptomic data.
AB  - BACKGROUND: The procedural aspects of genome sequencing and assembly have become
      relatively inexpensive, yet the full, accurate structural annotation of these
      genomes remains a challenge. Next-generation sequencing transcriptomics (RNA
      Seq), global microarrays, and tandem mass spectrometry (MS/MS)-based proteomics
      have demonstrated immense value to genome curators as individual sources of
      information, however, integrating these data types to validate and improve
      structural annotation remains a major challenge. Current visual and statistical
      analytic tools are focused on a single data type, or existing software tools are
      retrofitted to analyze new data forms. We present Visual Exploration and
      Statistics to Promote Annotation (VESPA) is a new interactive visual analysis
      software tool focused on assisting scientists with the annotation of prokaryotic
      genomes though the integration of proteomics and transcriptomics data with
      current genome location coordinates. RESULTS: VESPA is a desktop JavaTM
      application that integrates high-throughput proteomics data (peptide-centric) and
      transcriptomics (probe or RNA-Seq) data into a genomic context, all of which can
      be visualized at three levels of genomic resolution. Data is interrogated via
      searches linked to the genome visualizations to find regions with high likelihood
      of mis-annotation. Search results are linked to exports for further validation
      outside of VESPA or potential coding-regions can be analyzed concurrently with
      the software through interaction with BLAST. VESPA is demonstrated on two use
      cases (Yersinia pestis Pestoides F and Synechococcus sp. PCC 7002) to demonstrate
      the rapid manner in which mis-annotations can be found and explored in VESPA
      using either proteomics data alone, or in combination with transcriptomic data.
      CONCLUSIONS: VESPA is an interactive visual analytics tool that integrates high
      throughput data into a genomic context to facilitate the discovery of structural
      mis-annotations in prokaryotic genomes. Data is evaluated via visual analysis
      across multiple levels of genomic resolution, linked searches and interaction
      with existing bioinformatics tools. We highlight the novel functionality of VESPA
      and core programming requirements for visualization of these large heterogeneous
      datasets for a client-side application. The software is freely available at
      https://www.biopilot.org/docs/Software/Vespa.php.

PMID- 22480258
TI  - Bone marrow-derived cells implanted into radiation-injured urinary bladders
      reconstruct functional bladder tissues in rats.
AB  - The purpose of this study was to determine whether bone marrow-derived cells
      implanted into radiation-injured urinary bladders could reconstruct functional
      bladder tissues. The pelvic region of anesthetized female Sprague-Dawley (SD)
      rats was irradiated with 2 Gy once a week for 5 weeks. After the last
      irradiation, the rats were maintained for 2 weeks. Bone marrow cells were
      harvested from the femurs of donor male green fluorescence protein (GFP)
      transfected SD rats and cultured for 7 days. Two weeks after the last radiation
      exposure, the cultured adherent, proliferating bone marrow-derived cells were
      implanted into the walls of irradiated urinary bladders. For controls, cell-free
      solutions were similarly injected. Four weeks after donor cell or control
      implantations, cystometric, histological, and immunohistochemical investigations
      were performed. Two weeks after the last irradiation, the smooth muscle layers
      and nerve fibers of the irradiated urinary bladders were disorganized. The
      proportions of smooth muscle layer and nerve fiber areas were significantly
      decreased compared with sham-irradiated urinary bladders. In addition, the
      remaining smooth muscle cells within the irradiated urinary bladders expressed
      P4HB, an indicator of collagen synthesis. In the cystometric investigations, the
      voiding interval of irradiated rats was irregularly prolonged, 7.92+/-1.09 min,
      and the residual volume, 0.13+/-0.03 mL, was significantly higher compared with
      the sham-irradiated rats (5.50+/-0.43 mL and 0.05+/-0.01 mL). After 4 weeks, the
      smooth muscle layers and nerve fibers in the cell-free control urinary bladders
      remained similar to the preimplanted irradiated urinary bladders; however, the
      cell-implanted urinary bladders contained reconstructed smooth muscle layers and
      nerve fibers, the proportions of each were significantly higher than those in the
      cell-free injected controls. The expression of P4HB within the cell-implanted
      urinary bladders decreased. Some GFP-positive implanted cells differentiated into
      smooth muscle- and nerve-like cells and became organized into the reconstructed
      tissues. The voiding interval of the cell-implanted rats, 5.46+/-0.33 min, was
      regular and similar to that of the sham-irradiated rats, and significantly less
      than that of the cell-free injected controls, 7.39+/-0.54 min. The residual
      volume, 0.04+/-0.01 mL, was similar to that of the sham-irradiated rats and
      significantly decreased compared with that of the cell-free injected controls,
      0.15+/-0.05 mL. Therefore, the implantation of bone marrow-derived cells is a
      potentially useful treatment for radiotherapy-induced urinary dysfunctions.

PMID- 22480259
TI  - Dendrimer-driven neurotrophin expression differs in temporal patterns between
      rodent and human stem cells.
AB  - This study reports the use of a nonviral expression system based on
      polyamidoamine dendrimers for time-restricted neurotrophin overproduction in
      mesenchymal stem cells and skin precursor-derived Schwann cells. The dendrimers
      were used to deliver plasmids for brain-derived neurotrophic factor (BDNF) or
      neurotrophin-3 (NT-3) expression in both rodent and human stem cells, and the
      timelines of expression were studied. We have found that, despite the fact that
      transfection efficiencies and protein expression levels were comparable,
      dendrimer-driven expression in human mesenchymal stem cells was characterized by
      a more rapid decline compared to rodent cells. Transient expression systems can
      be beneficial for some neurotrophins, which were earlier reported to cause
      unwanted side effects in virus-based long-term expression models. Nonviral
      neurotrophin expression is a biologically safe and accessible alternative to
      increase the therapeutic potential of autologous adult stem cells and stem cell
      derived functional differentiated cells.

PMID- 22480260
TI  - Grape epicatechin conjugates prevent erythrocyte membrane protein oxidation.
AB  - Epicatechin conjugates obtained from grape have shown antioxidant activity in
      various systems. However, how these conjugates exert their antioxidant benefits
      has not been widely studied. We assessed the activity of epicatechin and
      epicatechin conjugates on the erythrocyte membrane in the presence and absence of
      a peroxyl radical initiator, to increase our understanding of their mechanisms.
      Thus, we studied cell membrane fluidity by fluorescence anisotropy measurements,
      morphology of erythrocytes by scanning electron microscopy, and finally, red cell
      membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Our data showed that incubation of red cells in the presence of epicatechin
      derivatives altered membrane fluidity and erythrocyte morphology but not the
      membrane protein pattern. The presence in the medium of the peroxyl radical
      initiator 2,2'-azobis(amidinopropane) dihydrochloride (AAPH) resulted in membrane
      disruptions at all levels analyzed, causing changes in membrane fluidity, cell
      morphology, and protein degradation. The presence of antioxidants avoided protein
      oxidation, indicating that the interaction of epicatechin conjugates with the
      lipid bilayer might reduce the accessibility of AAPH to membranes, which could
      explain in part the inhibitory ability of these compounds against hemolysis
      induced by peroxidative insult.

PMID- 22480261
TI  - Schistosomicidal evaluation of flavonoids from two species of Styrax against
      Schistosoma mansoni adult worms.
AB  - CONTEXT: Schistosomiasis is a major health problem worldwide. Thus, the search
      for new schistosomicidal agents from natural sources can provide prototypes for
      drug discovery. OBJECTIVE: The present study investigated the chemical
      composition of the EtOAc fractions of Styrax pohlii Pohl (Styracaceae) (EF-SP)
      aerial parts and S. camporum A. DC. leaves (EF-SC), as well as schistosomicidal
      activities against Schistosoma mansoni adult worms, which have not yet been
      studied. MATERIALS AND METHODS: The crude ethanol extracts of S. camporum leaves
      and S. pohlii aerial parts (EE-SC and EE-SP) were partitioned with n-hexane,
      EtOAc, and n-BuOH. The EtOAc fractions were purified by preparative HPLC. The
      crude extracts, EtOAc fractions and pure compounds were tested against S. mansoni
      adult worms in vitro. RESULTS: The purification procedure resulted in the
      isolation of kaempferol-3-O-(2'',4''-di-O-(E)-p-coumaroyl)-beta-d-glucopyranoside
      (1), kaempferol-3-O-(2'',6''-di-O-(E)-p-coumaroyl)-beta-d-glucopyranoside (2),
      quercetin (3), and kaempferol (4). The bioassay results indicated that EE-SC, EF
      SC, EF-SP, and compounds 2 and 4 are able to separate coupled S. mansoni adult
      worms. Additionally, EE-SC, EF-SP, and compound 4 killed the adult schistosomes
      in vitro at 100 ug/mL and 100 uM. DISCUSSION AND CONCLUSION: This is the first
      time that the presence of compounds 1-2 in S. pohlii and 3-4 in S. camporum has
      been reported. Additionally, biological results indicated that S. pohlii and S.
      camporum have great potential as a source of active compounds.

PMID- 22480262
TI  - Facial lesions in piglets with intact or grinded teeth.
AB  - BACKGROUND: Piglets are born with eight sharp teeth that during nursing can cause
      facial lesions on littermates and teat lesions on the sow. Teeth grinding in
      piglets is therefore often practiced to reduce these lesions. The aim of this
      study was to assess the consequences of grinding piglet teeth in regard to the
      occurrence of lesions.In this study the piglets' teeth were grinded in 28
      litters, and in 36 litters the piglets' teeth were kept intact. Twice, one time
      during the first week and one time during the second week after birth facial
      lesions of the piglets were scored and the teats of the sows were examined for
      lesions. The facial lesion score accounted for the amount and severity of
      lesions. The individual observations on piglets in the litter were synthesized in
      a litter facial lesion score. FINDINGS: 69.8% and 43.5% of the piglets had facial
      lesions in week 1 and week 2 respectively. The effect of treatment was not
      significant on litter facial lesion score. The litter facial lesion score was
      higher in week 1 than in week 2 (p < 0.001) and higher in large litters (p =
      0.003) than in small litters. Mortality between week 1 and week 2 was higher in
      litters with intact teeth (p = 0.02). Sow teat lesions only occurred if litters
      had intact teeth. CONCLUSIONS: According to our results teeth grinding is only
      justifiable in large litters.

PMID- 22480263
TI  - Ruthenium(II)-catalyzed regio- and stereoselective hydroarylation of alkynes via
      directed C-H functionalization.
AB  - The ruthenium-catalyzed hydroarylation of alkynes with benzamides proceeds regio-
      and stereoselectively through a directed C-H bond cleavage. Preliminary
      mechanistic investigations indicate that the reaction involves amide-directed
      ortho-metalation, carbometalation of alkyne, and protonolysis. Similarly,
      phenylazoles also add to alkynes regioselectively.

PMID- 22480265
TI  - Life cycle environmental impacts of three products derived from wild-caught
      Antarctic krill (Euphausia superba).
AB  - Concern has been voiced in recent years regarding the environmental implications
      of the Antarctic krill fishery. Attention has focused primarily on ecological
      concerns, whereas other environmental aspects, including potentially globally
      problematic emissions and material and energy demands, have not been examined in
      detail. Here we apply life cycle assessment to measure the contributions of krill
      meal, oil, and omega-3 capsules to global warming, ozone depletion,
      acidification, eutrophication, energy use, and biotic resource use. Supply chains
      of one krill fishing and processing company, Aker BioMarine of Norway, were
      assessed. Impacts of krill products were found to be driven primarily by the
      combustion of fossil fuels onboard the fishing vessel and a transport/resupply
      vessel. Approximately 190 L of fuel are burned per tonne of raw krill landed,
      markedly higher than fuel inputs to reduction fisheries targeting other species.
      In contrast, the biotic resource use associated with extracting krill is
      relatively low compared to that of other reduction fisheries. Results of this
      study provide insight into the broader environmental implications of the krill
      fishery, comparisons between products derived from krill and other species
      targeted for reduction, opportunities for improving the fishery's performance,
      and a baseline against which to measure future performance.

PMID- 22480264
TI  - Structural and functional consequences of phosphate-arsenate substitutions in
      selected nucleotides: DNA, RNA, and ATP.
AB  - A recent finding of a bacterial strain (GFAJ-1) that can rely on arsenic instead
      of phosphorus raised the questions of if and how arsenate can replace phosphate
      in biomolecules that are essential to sustain cell life. Apart from questions
      related to chemical stability, there are those of the structural and functional
      consequences of phosphate-arsenate substitutions in vital nucleotides in GFAJ1
      like cells. In this study we selected three types of molecules (ATP/ADP as energy
      source and replication regulation; DNA-protein complexes for DNA replication and
      transcription initiation; and a tRNA-protein complex and ribosome for protein
      synthesis) to computationally probe if arsenate nucleotides can retain the
      structural and functional features of phosphate nucleotides. Hydrolysis of
      adenosine triarsenate provides 2-3 kcal/mol less energy than ATP hydrolysis.
      Arsenate DNA/RNA interacts with proteins slightly less strongly than phosphate
      DNA/RNA, mainly due to the weaker electrostatic interactions of arsenate. We
      observed that the weaker arsenate RNA-protein interactions may hamper rRNA
      assembly into a functional ribosome. We further compared the experimental EXAFS
      spectra of the arsenic bacteria with theoretical EXAFS spectra for arsenate DNA
      and rRNA. Our results demonstrate that while it is possible that dried GFAJ-1
      cells contain linear arsenate DNA, the arsenate 70S ribosome does not contribute
      to the main arsenate depository in the GFAJ-1 cell. Our study indicates that
      evolution has optimized the inter-relationship between proteins and DNA/RNA,
      which requires overall changes at the molecular and systems biology levels when
      replacing phosphate by arsenate. 

PMID- 22480266
TI  - Preparation, characterization, sterility validation, and in vitro cell toxicity
      studies of microemulsions possessing potential parenteral applications.
AB  - CONTEXT: Water-in-oil microemulsions (w/o ME) are ideal for parenteral drug
      delivery. However, no such formulations have been tested for biocompatibility in
      in vitro cell cultures. Furthermore, sterilization of w/o MEs is a challenging
      process that has not been previously developed and validated. PURPOSE: To
      formulate pharmaceutically relevant water-in-oil (w/o) microemulsion's systems
      suitable for use as a parenteral formulation. METHODS: w/o MEs were prepared
      using dioctyl sodium sulfosuccinate (DOSS), ethyl oleate (EO), and water.
      Formulations were characterized using polarized light microscopy, electrical
      conductivity, rheology, and dynamic light scattering. An aseptic filtration
      method for sterilization was developed using membrane filtration. The
      biocompatibility of selected MEs were evaluated in NIH3T3 cell cultures.
      Dissolution studies were performed on microemulsions containing methylene blue to
      evaluate the drug release profile. RESULTS: The maximum amount of water
      incorporated in the formulations was 14% w/w. DOSS/EO/water microemulsions
      exhibited Newtonian flow. Particle sizes for these MEs were less than 30 nm in
      size. Formulations filtered aseptically were free of bacteria when gram-stained
      and visualized under a microscope. All MEs showed no toxicity to NIH 3T3 cells.
      DISCUSSION: The absence of birefringence and low conductivity values indicated
      that the formulations were w/o microemulsions. The filtration method of
      sterilization was validated by the absence of microbial growth on blood agar
      plates over a 14-day period. In vitro dye release studies demonstrate sustained
      release of the model drug over a 72-h time period. CONCLUSION: Characteristics
      delineated in this study demonstrate the potential for these formulations to be
      used as parenteral preparations.

PMID- 22480267
TI  - Membrane phase behavior during cooling of stallion sperm and its correlation with
      freezability.
AB  - Stallion sperm exhibits great male-to-male variability in survival after
      cryopreservation. In this study, we have investigated if differences in sperm
      freezability can be attributed to membrane phase and permeability properties.
      Fourier transform infrared spectroscopy (FTIR) was used to determine supra and
      subzero membrane phase transitions and characteristic subzero membrane hydraulic
      permeability parameters. Sperm was obtained from stallions that show differences
      in sperm viability after cryopreservation. Stallion sperm undergoes a broad and
      gradual phase transition at suprazero temperatures, from 30-10 degrees C, whereas
      freezing-induced dehydration of the cells causes a more severe phase transition
      to a highly ordered gel phase. Sperm from individual stallions showed significant
      differences in post-thaw progressive motility, percentages of sperm with abnormal
      cell morphology, and chromatin stability. The biophysical membrane properties
      evaluated in this study, however, did not show clear differences amongst
      stallions with differences in sperm freezability. Cyclodextrin treatment to
      remove cholesterol from the cellular membranes increased the cooperativity of the
      suprazero phase transition, but had little effects on the subzero membrane phase
      behavior. In contrast, freezing of sperm in the presence of protective agents
      decreased the rate of membrane dehydration and increased the total extent of
      dehydration. Cryoprotective agents such as glycerol decrease the amount of energy
      needed to transport water across cellular membranes during freezing.

PMID- 22480270
TI  - General and selective copper-catalyzed reduction of tertiary and secondary
      phosphine oxides: convenient synthesis of phosphines.
AB  - Novel catalytic reductions of tertiary and secondary phosphine oxides to
      phosphines have been developed. Using tetramethyldisiloxane (TMDS) as a mild
      reducing agent in the presence of copper complexes, PO bonds are selectively
      reduced in the presence of other reducible functional groups (FGs) such as
      ketones, esters, and olefins. Based on this transformation, an efficient one pot
      reduction/phosphination domino sequence allows for the synthesis of a variety of
      functionalized aromatic and aliphatic phosphines in good yields.

PMID- 22480269
TI  - Cardiovascular magnetic resonance evaluation of aortic stenosis severity using
      single plane measurement of effective orifice area.
AB  - BACKGROUND: Transthoracic echocardiography (TTE) is the standard method for the
      evaluation of the severity of aortic stenosis (AS). Valve effective orifice area
      (EOA) measured by the continuity equation is one of the most frequently used
      stenotic indices. However, TTE measurement of aortic valve EOA is not feasible or
      not reliable in a significant proportion of patients. Cardiovascular magnetic
      resonance (CMR) has emerged as a non-invasive alternative to evaluate EOA using
      velocity measurements. The objectives of this study were: 1) to validate a new
      CMR method using jet shear layer detection (JSLD) based on acoustical source term
      (AST) concept to estimate the valve EOA; 2) to introduce a simplified JSLD method
      not requiring vorticity field derivation. METHODS AND RESULTS: We performed an in
      vitro study where EOA was measured by CMR in 4 fixed stenoses (EOA = 0.48, 1.00,
      1.38 and 2.11 cm2) under the same steady flow conditions (4-20 L/min). The in
      vivo study included eight (8) healthy subjects and 37 patients with mild to
      severe AS (0.72 cm2 <= EOA <= 1.71 cm2). All subjects underwent TTE and CMR
      examinations. EOA was determinated by TTE with the use of continuity equation
      method (TTE(CONT)). For CMR estimation of EOA, we used 3 methods: 1) Continuity
      equation (CMR(CONT)); 2) Shear layer detection (CMR(JSLD)), which was computed
      from the velocity field of a single CMR velocity profile at the peak systolic
      phase; 3) Single plane velocity truncation (CMR(SPVT)), which is a simplified
      version of CMR(JSLD) method. There was a good agreement between the EOAs obtained
      in vitro by the different CMR methods and the EOA predicted from the potential
      flow theory. In the in vivo study, there was good correlation and concordance
      between the EOA measured by the TTE(CONT) method versus those measured by each of
      the CMR methods: CMR(CONT) (r = 0.88), CMR(JSLD) (r = 0.93) and CMR(SPVT) (r =
      0.93). The intra- and inter- observer variability of EOA measurements was 5 +/-
      5% and 9 +/- 5% for TTE(CONT), 2 +/- 1% and 7 +/- 5% for CMR(CONT), 7 +/- 5% and
      8 +/- 7% for CMR(JSLD), 1 +/- 2% and 3 +/- 2% for CMR(SPVT). When repeating image
      acquisition, reproducibility of measurements was 10 +/- 8% and 12 +/- 5% for
      TTE(CONT), 9 +/- 9% and 8 +/- 8% for CMR(CONT), 6 +/- 5% and 7 +/- 4% for
      CMR(JSLD) and 3 +/- 2% and 2 +/- 2% for CMR(SPVT). CONCLUSION: There was an
      excellent agreement between the EOA estimated by the CMR(JSLD) or CMR(SPVT)
      methods and: 1) the theoretical EOA in vitro, and 2) the TTE(CONT) EOA in vivo.
      The CMR(SPVT) method was superior to the TTE and other CMR methods in terms of
      measurement variability. The novel CMR-based methods proposed in this study may
      be helpful to corroborate stenosis severity in patients for whom Doppler
      echocardiography exam is inconclusive.

PMID- 22480268
TI  - Systematic review of diarrhea duration and severity in children and adults in low
      and middle-income countries.
AB  - BACKGROUND: Diarrhea is a leading cause of morbidity and mortality globally; yet
      the overall burden of diarrhea in terms of duration and severity has not been
      quantified. As improvements in treatment lead to decreases in diarrhea mortality,
      it is important to understand the substantial impact of diarrhea morbidity on
      disability among children and adults worldwide. METHODS: We conducted a
      systematic review to generate estimates of duration and severity outcomes for
      individuals 0-59 mos, 5-15 yrs, and >= 16 yrs, and for 3 severity indexes: mild,
      moderate, and severe. RESULTS: We estimate that among children under-five, 64.8%
      of diarrheal episodes are mild, 34.7% are moderate, and 0.5% are severe. On
      average, mild episodes last 4.3 days, and severe episodes last 8.4 days and cause
      dehydration in 84.6% of cases. We estimate that among older children and adults,
      95% of episodes are mild; 4.95% are moderate; and 0.05% are severe. Among
      individuals >= 16 yrs, severe episodes typically last 2.6 days and cause
      dehydration in 92.8% of cases. CONCLUSIONS: Moderate and severe episodes
      constitute a substantial portion of the total envelope of diarrhea among children
      under-five (35.2%; about 588 million episodes). Among older children and adults,
      moderate and severe episodes account for a much smaller proportion of the total
      envelope of diarrhea (5%), but the absolute number of such episodes is noteworthy
      (about 21.5 million episodes among individuals >= 16 yrs). Hence, the global
      burden of diarrhea consists of significant morbidity, extending beyond episodes
      progressing to death.

PMID- 22480271
TI  - CacyBP/SIP phosphatase activity in neuroblastoma NB2a and colon cancer HCT116
      cells.
AB  - Recently, we have reported that CacyBP/SIP could be a novel phosphatase for
      ERK1/2 kinase. In this work, we analyzed the CacyBP/SIP phosphatase activity
      toward ERK1/2 in 2 cell lines of different origin. We showed that overexpression
      of CacyBP/SIP in NB2a cells resulted in a lower level of phosphorylated ERK1/2 (P
      ERK1/2) in the nuclear fraction while such overexpression in HCT116 cells had no
      effect on the level of P-ERK1/2. Moreover, we found that overexpression of
      CacyBP/SIP resulted in higher phosphatase activity in the nuclear fraction
      obtained from NB2a cells when compared with HCT116 cells. Using 2-D
      electrophoresis we showed that the pattern of spots representing CacyBP/SIP
      differed in these 2 cell lines and was probably due to a different
      phosphorylation state of this protein. We also established that after
      overexpression of CacyBP/SIP in NB2a cells, the amount of nuclear beta-catenin
      was low, while it remained high in HCT116 cells. Since NB2a cells have
      differentiation potential and HCT116 cells do not, our data suggest that
      different activity of CacyBP/SIP in these 2 cell lines might affect the ERK1/2
      pathway in the differentiation or proliferation processes.

PMID- 22480272
TI  - Realizing the potential of accessible ICTs in developing countries.
AB  - PURPOSE: To raise the awareness of policy makers, economic development
      practitioners, and service providers about the importance of making information
      and communication technology (ICT) based international economic development in
      low- and middle-income countries inclusive of people with disabilities and to
      discuss the role and importance of addressing the complete ICT and assistive
      technology (AT) ecosystem to ensure sustainable, scalable, and affordable access
      to ICTs and ICT-based programs. METHOD: This commentary piece draws upon recent
      literature and practice cases to examine the role of accessible ICTs in
      international development. RESULTS: Accessible ICTs can enhance economic
      participation and prevent exclusion from participation in international
      development programs. Access to and use of accessible technologies are largely
      determined by the ecosystem in which they exist and can be enhanced or hindered
      by government policy and legislation and the quality of the service delivery
      systems and financing mechanisms. CONCLUSIONS: People with disabilities in
      developing countries face daunting barriers to socioeconomic participation.
      Accessible ICTs can eliminate or mitigate some of these barriers. However,
      technology advancements do not solely promote penetration, affordability, or
      scalability of ICT-based development for persons with disabilities. A
      comprehensive ecosystem approach can help in developing sustainable mechanisms
      for access, affordability, and availability.

PMID- 22480273
TI  - Tav4SB: integrating tools for analysis of kinetic models of biological systems.
AB  - BACKGROUND: Progress in the modeling of biological systems strongly relies on the
      availability of specialized computer-aided tools. To that end, the Taverna
      Workbench eases integration of software tools for life science research and
      provides a common workflow-based framework for computational experiments in
      Biology. RESULTS: The Taverna services for Systems Biology (Tav4SB) project
      provides a set of new Web service operations, which extend the functionality of
      the Taverna Workbench in a domain of systems biology. Tav4SB operations allow you
      to perform numerical simulations or model checking of, respectively,
      deterministic or stochastic semantics of biological models. On top of this
      functionality, Tav4SB enables the construction of high-level experiments. As an
      illustration of possibilities offered by our project we apply the multi-parameter
      sensitivity analysis. To visualize the results of model analysis a flexible
      plotting operation is provided as well. Tav4SB operations are executed in a
      simple grid environment, integrating heterogeneous software such as Mathematica,
      PRISM and SBML ODE Solver. The user guide, contact information, full
      documentation of available Web service operations, workflows and other additional
      resources can be found at the Tav4SB project's Web page:
      http://bioputer.mimuw.edu.pl/tav4sb/. CONCLUSIONS: The Tav4SB Web service
      provides a set of integrated tools in the domain for which Web-based applications
      are still not as widely available as for other areas of computational biology.
      Moreover, we extend the dedicated hardware base for computationally expensive
      task of simulating cellular models. Finally, we promote the standardization of
      models and experiments as well as accessibility and usability of remote services.

PMID- 22480274
TI  - Rapid method for proline determination in grape juice and wine.
AB  - Proline is typically the most abundant amino acid present in grape juice and
      wine. The amount present is influenced by viticultural and winemaking factors and
      can be of diagnostic importance. A method for rapid routine quantitation of
      proline would therefore be of benefit for wine researchers and the industry in
      general. Colorimetric determination utilizing isatin as a derivatizing agent has
      previously been applied to plant extracts, biological fluids, and protein
      hydrolysates. In the current study, this method has been successfully adapted to
      grape juice and wine and proved to be sensitive to milligram per liter amounts of
      proline. At sugar concentrations above 60 g/L, interference from the isatin
      proline reaction was observed, such that proline concentrations were considerably
      underestimated in grape juice and dessert wine. However, the method was robust
      for the analysis of fermentation samples and table wines. Results were within +/
      10% agreement with data generated from typical HPLC-based analyses. The isatin
      method is therefore considered suitable for the routine analysis required to
      support research into the utilization or release of proline by yeast during
      fermentation.

PMID- 22480275
TI  - Local biochemical and morphological differences in human Achilles tendinopathy: a
      case control study.
AB  - BACKGROUND: The incidence of Achilles tendinopathy is high and underlying
      etiology as well as biochemical and morphological pathology associated with the
      disease is largely unknown. The aim of the present study was to describe
      biochemical and morphological differences in chronic Achilles tendinopathy. The
      expressions of growth factors, inflammatory mediators and tendon morphology were
      determined in both chronically diseased and healthy tendon parts. METHODS: Thirty
      Achilles tendinopathy patients were randomized to an expression-study (n = 16) or
      a structural-study (n = 14). Biopsies from two areas in the Achilles tendon were
      taken and structural parameters: fibril density, fibril size, volume fraction of
      cells and the nucleus/cytoplasm ratio of cells were determined. Further gene
      expressions of various genes were analyzed. RESULTS: Significantly smaller
      collagen fibrils and a higher volume fraction of cells were observed in the
      tendinopathic region of the tendon. Markers for collagen and its synthesis
      collagen 1, collagen 3, fibronectin, tenascin-c, transforming growth factor-beta
      fibromodulin, and markers of collagen breakdown matrix metalloproteinase-2,
      matrix metalloproteinase-9 and metallopeptidase inhibitor-2 were significantly
      increased in the tendinopathic region. No altered expressions of markers for
      fibrillogenesis, inflammation or wound healing were observed. CONCLUSION: The
      present study indicates that an increased expression of factors stimulating the
      turnover of connective tissue is present in the diseased part of tendinopathic
      tendons, associated with an increased number of cells in the injured area as well
      as an increased number of smaller and thinner fibrils in the diseased tendon
      region. As no fibrillogenesis, inflammation or wound healing could be detected,
      the present data supports the notion that tendinopathy is an ongoing degenerative
      process. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20896880.

PMID- 22480276
TI  - Improving the cell distribution in collagen-coated poly-caprolactone knittings.
AB  - Adequate cellular in-growth into biomaterials is one of the fundamental
      requirements of scaffolds used in regenerative medicine. Type I collagen is the
      most commonly used material for soft tissue engineering, because it is
      nonimmunogenic and a highly porous network for cellular support can be produced.
      However, in general, adequate cell in-growth and cell seeding has been
      suboptimal. In this study we prepared collagen scaffolds of different collagen
      densities and investigated the cellular distribution. We also prepared a hybrid
      polymer-collagen scaffold to achieve an optimal cellular distribution as well as
      sufficient mechanical strength. Collagen scaffolds [ranging from 0.3% to 0.8%
      (w/v)] with and without a mechanically stable polymer knitting [poly-caprolactone
      (PCL)] were prepared. The porous structure of collagen scaffolds was
      characterized using scanning electron microscopy and hematoxylin-eosin staining.
      The mechanical strength of hybrid scaffolds (collagen with or without PCL) was
      determined using tensile strength analysis. Cellular in-growth and
      interconnectivity were evaluated using fluorescent bead distribution and human
      bladder smooth muscle cells and human urothelium seeding. The lower density
      collagen scaffolds showed remarkably deeper cellular penetration and by combining
      it with PCL knitting the tensile strength was enhanced. This study indicated that
      a hybrid scaffold prepared from 0.4% collagen strengthened with knitting achieved
      the best cellular distribution.

PMID- 22480277
TI  - Hepatoprotective activity of Indian Phyllanthus.
AB  - CONTEXT: Phyllanthus (Euphorbiaceae) species are traditionally well-known for
      their medicinal properties including hepatoprotective activity. OBJECTIVE: The
      study assessed the hepatoprotective and antioxidant activities of 11 Phyllanthus
      species, P. amarus Schumach., P. urinaria L., P. debilis Klein ex Willd, P.
      tenellus Roxb., P. virgatus G. Forst., P. maderaspatensis L., P. reticulatus
      Poir., P. polyphyllus Willd., P. emblica L., P. indofischerii Bennet. and P.
      acidus (L.) Skeels. MATERIALS AND METHODS: The dried leaves and stems of each
      plant species were extracted in methanol and successively in water. The extracts
      were screened for hepatoprotective activity at a concentration of 50 ug/mL
      against tert-butyl hydroperoxide (t-BH) induced toxicity in HepG2 cells. Seven
      extracts from five species that showed hepatoprotective activity were assessed
      for their 50% effective concentration (EC50) values and their antioxidant
      activity using a DPPH assay. Phyllanthin and hypophyllanthin contents were also
      determined in these Phyllanthus species. RESULTS: The methanol extracts of P.
      polyphyllus, P. emblica and P. indofischeri showed high levels of
      hepatoprotective activity with EC50 values of 12, 19 and 28 ug/mL and IC50 of
      3.77, 3.38 and 5.8 ug/mL for DPPH scavenging activity respectively against an
      IC50 of 3.69 ug/mL for ascorbic acid. None of these activities could be
      attributed to phyllanthin and hypophyllanthin. DISCUSSION AND CONCLUSION: The
      hepatoprotective and antioxidant activities of P. indofischeri are demonstrated
      for the first time in literature. The study also confirms the hepatoprotective
      and antioxidant activities of leaves of P. emblica and P. polyphyllus. The
      molecule(s) responsible for the activities is being investigated.

PMID- 22480278
TI  - A descriptive study of chiropractors' opinions and practices regarding office
      based health product sales.
AB  - BACKGROUND: Although the sale of non-prescription health products is ubiquitous,
      the views of health professionals, such as chiropractors, regarding the sale of
      such products are not well known. Practitioner opinion is important to understand
      and inform professional practice. The purpose of this study was to describe
      chiropractors' perspectives and practices on the sale of health care products
      from practitioners' offices. METHODS: Chiropractors were invited to provide
      written comments about health product sales at the end of a fixed choice, mailed
      survey. Respondents' comments were analyzed using qualitative description. Ethics
      approval was received from the Conjoint Health Research Ethics Board at the
      University of Calgary. RESULTS: One hundred seven of the 265 respondents
      (response rate of 51%) provided written comments. Approximately 30 pages of
      double-spaced, typed text were gathered. Respondents did not consistently endorse
      or condemn health product sales, and engaged in the practice to greater and
      lesser extents. While some were opposed to health products sales, some accepted
      the practice with a degree of ambivalence whereas others clearly embraced it.
      Some respondents acknowledged a professional conflict of interest in such sales
      and marketing, and described strategies used to mitigate it. Others provided a
      range of justifications for the practice. Personal integrity and professional
      standards were discussed and a need for monitoring identified. CONCLUSIONS: A
      wide range of opinions and practices were described and this is consistent with
      resulting variation in practice. In light of this, standards that facilitate
      consistency in practice may benefit professionals and the public alike.

PMID- 22480279
TI  - Pain alleviation and patient-reported health outcomes following switching to
      pregabalin in individuals with gabapentin-refractory neuropathic pain in routine
      medical practice.
AB  - BACKGROUND: It has been suggested that peripheral neuropathic pain (PNP) may
      affect up to 3% of the general population. PNP has a substantial negative impact
      on patient functioning and quality of life, including reduced productivity and
      increased consumption of healthcare resources. OBJECTIVE: The objective of this
      study was to analyse changes in pain and patient-reported health outcomes
      following switching to pregabalin treatment in patients with gabapentin
      refractory PNP as part of routine clinical practice in Spanish primary-care
      settings. METHODS: This was an open-label, non-randomized, post hoc analysis of a
      12-week, multicentre, non-interventional cost-of-illness study. The study
      involved primary-care physicians and was carried out between September 2005 and
      April 2006. Patients were aged at least 18 years and had chronic, treatment
      refractory PNP. The analysis included all pregabalin-naive patient switches that
      had previously shown an inadequate response to gabapentin. The following
      variables were assessed before and after pregabalin therapy: pain (Short-Form
      McGill Pain Questionnaire [SF-MPQ]), disability level (Sheehan Disability Scale
      [SDS]), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale
      [HADS]), self-perceived sleep quality and quantity (Medical Outcomes Study [MOS]
      Sleep Scale), and health-related quality of life (EuroQol [EQ] five-dimension
      [5D] questionnaire). RESULTS: A total of 174 patients with an inadequate response
      to gabapentin switched to pregabalin at the beginning of the study. After 12
      weeks of pregabalin therapy, alone or in combination with other analgesic drugs,
      significant and clinically relevant improvements were observed in pain severity
      [mean (SD) SF-MPQ change: -31.9 (22.1) points; 42.5% being responders (pain
      reduction >=50%)], disability [SDS score: -7.5 (6.2) vs baseline], affective
      symptoms [HADS depression: -4.5 (3.9); HADS anxiety: -4.1 (3.7)], sleep [MOS
      summary index: -17.2 (16.6)], and health status [EQ-5D visual analogue scale
      (VAS): 27.3 (18.2)], with an overall gain of 0.040 (0.031) quality-adjusted life
      years. CONCLUSION: These findings suggest that pregabalin could be a valid
      treatment alternative for the management of patients with gabapentin-refractory
      peripheral neuropathic pain in primary-care settings under real-life conditions
      of care. Our data show that patients who were switched to pregabalin, either as
      monotherapy or in combination with other analgesics, showed substantial and
      clinically relevant improvements in relieving pain and related symptoms.

PMID- 22480280
TI  - alpha1-Proteinase inhibitor (human) in the treatment of hereditary emphysema
      secondary to alpha1-antitrypsin deficiency: number and costs of years of life
      gained.
AB  - BACKGROUND: alpha(1)-Antitrypsin deficiency (alpha-ATD) is a disorder inherited
      in an autosomal recessive pattern, with co-dominant alleles known as the protease
      inhibitor system (Pi). The main function of alpha(1)-antitrypsin (alpha-AT) is to
      protect the lungs against a powerful elastase released from neutrophil
      leucocytes. alpha-ATD typically presents with a serum alpha-AT level of <50
      mg/dL. In severe alpha-ATD, phenotype PiZZ, protection of the lungs is
      compromised, leading to an accelerated decline in forced expiratory volume in 1
      second (FEV(1)). As a result, a patient may develop pulmonary emphysema of the
      panacinar type at a young age (third to fourth decades of life), with cigarette
      smoking being the most significant additional risk factor. It has been shown that
      weekly or monthly infusion of human alpha-AT is effective in raising serum alpha
      AT levels to desired levels (>80 mg/dL), with few, if any, adverse effects.
      OBJECTIVE: The present study was designed to discern the number of years of life
      gained, and the expense per year of life gained, associated with use of alpha-AT
      augmentation therapy (alpha(1)-proteinase inhibitor [human]), relative to 'no
      therapeutic intervention' in persons with alpha-ATD. METHODS: Monte Carlo
      simulation (MCS) was used to: (i) estimate the number of years of life gained;
      and (ii) estimate the health service expenditures per year of life gained for
      persons receiving, or not receiving, alpha-AT augmentation therapy. MCS afforded
      a decision-analytical framework parameterized with both stochastic (random) and
      deterministic (fixed) components, and yielded a fiscal risk-profile for each
      simulated cohort of interest (eight total: by sex, smoking status [non-smoker; or
      past use (smoker)]; and use of alpha-AT augmentation therapy). The stochastic
      components employed in the present inquiry were: (i) age-specific body weight,
      and height; (ii) age-specific mortality; and (iii) the probability distribution
      for receipt of a lung transplant, as a function of FEV(1). The deterministic
      components employed in the present inquiry were: (i) age in years for the
      simulated cohort; (ii) outlays for alpha-AT augmentation therapy; (iii) health
      service expenditures associated with receipt of a lung transplant; (iv) annual
      decline in FEV(1); (v) percent predicted FEV(1); (vi) initiation of alpha-AT
      augmentation therapy as a function of percent predicted FEV(1); (vii) need for a
      lung transplant as a function of percent predicted FEV(1); (viii) annual rate of
      lung infection; and (ix) mortality as a function of percent predicted FEV(1).
      Results are reported from a payer perspective ($US, year of costing 2010).
      RESULTS: Receipt of alpha-AT augmentation therapy was associated with a
      significant increase (p < 0.05) in years of life gained, with female smokers
      gaining an estimated mean 7.14 years (cost per year: $US248 361 [95% CI 104 531,
      392 190]); female non-smokers gained an estimated mean 9.19 years (cost per year:
      $US160 502 [95% CI 37 056, 283 947)]); male smokers gained an estimated mean 5.93
      years (cost per year: $US142 250 [95% CI 48 467, 236 032]); and male non-smokers
      gained an estimated mean 10.60 years (cost per year: $US59 234 [95% CI 20 719, 97
      548]). CONCLUSION: Use of alpha-AT augmentation therapy was associated with an
      increase in years of life gained by sex and history of tobacco use, and at a cost
      per year of life gained comparable to that of other evidenced-based
      interventions.

PMID- 22480281
TI  - Potential of the NBP method for the study of alkylation mechanisms: NBP as a DNA
      model.
AB  - Alkylating agents are considered to be archetypal carcinogens. One suitable
      technique to evaluate the activity of alkylating compounds is the NBP assay. This
      method is based on the formation of a chromophore in the reaction between the
      alkylating agent and the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for
      alkylating agents with nucleophilic characteristics similar to those of DNA
      bases. NBP is known to react with strong and weak alkylating agents, and much
      insight into such alkylation mechanisms in vivo can be gained from kinetic study
      of some alkylation reactions in vitro. Since 1925, the NBP assay has evolved from
      being a qualitative, analytical tool to becoming a useful physicochemical method
      that not only allows the rules of chemical reactivity that govern
      electrophilicity and nucleophilicity to be applied to the reaction of DNA with
      alkylating agents but also helps to understand some significant relationships
      between the structure of many alkylation substrates (including DNA) and their
      chemical and biological responses. Given that advances in this area have the
      potential to yield both fundamental and practical advances in chemistry, biology,
      predictive toxicology, and anticancer drug development, this review is designed
      to provide an overview of the evolution of the NBP method from its early
      inception until its recent kinetic-mechanistic approach, which allows the pros
      and cons of NBP as a DNA-model to be analyzed. The validity of NBP as a
      nucleophilicity model for DNA in general and the position of guanosine at N7 in
      particular are discussed.

PMID- 22480282
TI  - Vitamin D3-inducible mesenchymal stem cell-based delivery of conditionally
      replicating adenoviruses effectively targets renal cell carcinoma and inhibits
      tumor growth.
AB  - Cell-based carriers were recently exploited as a tumor-targeting tool to improve
      systemic delivery of oncolytic viruses for cancer therapy. However, the slow
      clearance of carrier cells from normal organs indicates the need for a
      controllable system which allows viral delivery only when the carrier cells reach
      the tumor site. In this study, we sought to develop a pharmaceutically inducible
      cell-based oncolytic adenovirus delivery strategy for effective targeting and
      treatment of renal cell carcinoma (RCC), which is one of the most malignant tumor
      types with an unfavorable prognosis. Herein, we demonstrated the intrinsic tumor
      homing property of human bone marrow-derived mesenchymal stem cells (hMSCs) to
      specifically localize primary and metastatic RCC tumors after systemic
      administration in a clinically relevant orthotopic animal model. The platelet
      derived growth factor AA (PDGF-AA) secreted from RCC was identified as a
      chemoattractant responsible for the recruitment of hMSCs. Like endogenous
      osteocalcin whose barely detectable level of expression was dramatically induced
      by vitamin D(3), the silenced replication of human osteocalcin promoter-directed
      Ad-hOC-E1 oncolytic adenoviruses loaded in hMSCs was rapidly activated, and the
      released oncolytic adenoviruses sequentially killed cocultured RCC cells upon
      vitamin D(3) exposure. Moreover, the systemic treatment of RCC tumor-bearing mice
      with hMSC cell carriers loaded with Ad-hOC-E1 had very limited effects on tumor
      growth, but the loaded hMSCs combined with vitamin D(3) treatment induced
      effective viral delivery to RCC tumors and significant tumor regression.
      Therapeutic effects of hMSC-based Ad-hOC-E1 delivery were confirmed to be
      significantly greater than those of injection of carrier-free Ad-hOC-E1. Our
      results presented the first preclinical demonstration of a novel controllable
      cell-based gene delivery strategy that combines the advantages of tumor tropism
      and vitamin D(3)-regulatable human osteocalcin promoter-directed gene expression
      of hMSCs to improve oncolytic virotherapy for advanced RCC.

PMID- 22480284
TI  - Synthesis of tetracyclic indoles via intramolecular alpha-arylation of ketones.
AB  - An intramolecular palladium(0)-mediated alpha-arylation of ketones applied to the
      synthesis of various substituted tetracyclic indoles is reported. Most
      significantly, the efficiency of the transformation was enhanced by the use of
      monoligated Pd(0) complexes. This methodology was extended to double alpha
      arylation of ketones using one-pot reactions with either simultaneous addition or
      sequential addition of two aryl halides for producing aryl substituted
      tetracyclic indoles.

PMID- 22480283
TI  - Transcriptome-wide identification and characterization of miRNAs from Pinus
      densata.
AB  - BACKGROUND: MicroRNAs (miRNAs) play key roles in diverse developmental processes,
      nutrient homeostasis and responses to biotic and abiotic stresses. The biogenesis
      and regulatory functions of miRNAs have been intensively studied in model
      angiosperms, such as Arabidopsis thaliana, Oryza sativa and Populus trichocarpa.
      However, global identification of Pinus densata miRNAs has not been reported in
      previous research. RESULTS: Here, we report the identification of 34 conserved
      miRNAs belonging to 25 miRNA families from a P. densata mRNA transcriptome
      database using local BLAST and MIREAP programs. The primary and/or precursor
      sequences of 29 miRNAs were further confirmed by RT-PCR amplification and
      subsequent sequencing. The average value of the minimal folding free energy
      indexes of the 34 miRNA precursors was 0.92. Nineteen (58%) mature miRNAs began
      with a 5' terminal uridine residue. Analysis of miRNA precursors showed that 19
      mature miRNAs were novel members of 14 conserved miRNA families, of which 17
      miRNAs were further validated by subcloning and sequencing. Using real-time
      quantitative RT-PCR, we found that the expression levels of 7 miRNAs were more
      than 2-fold higher in needles than in stems. In addition, 72 P. densata mRNAs
      were predicted to be targets of 25 miRNA families. Four target genes, including a
      nodal modulator 1-like protein gene, two GRAS family transcription factor protein
      genes and one histone deacetylase gene, were experimentally verified to be the
      targets of 3 P. densata miRNAs, pde-miR162a, pde-miR171a and pde-miR482a,
      respectively. CONCLUSIONS: This study led to the discovery of 34 conserved miRNAs
      comprising 25 miRNA families from Pinus densata. These results lay a solid
      foundation for further studying the regulative roles of miRNAs in the
      development, growth and responses to environmental stresses in P. densata.

PMID- 22480285
TI  - Microvascular diseases: is a new era coming?
AB  - The microvascular bed is an anatomical entity which comprises myriads of small
      arterioles, capillaries and venules. Microvessels and surrounding tissue
      metabolism are tightly coupled; consequently they are equipped with many, very
      specific and fine-tuned mechanisms allowing permanent, precise regulation of
      nutrient delivery. The review thoroughly describes the structure and physiology
      of arterioles and capillaries as well as the specialized means to investigate
      them. Microcirculation has been largely neglected for decades, mainly because of
      lack of technical possibilities for visualization and quantitation. However the
      past years have completely renewed the scientific interest, due to the
      combination of the availability of new techniques in human research and the
      recognition that the microcirculation is autonomically and causally involved in
      diseases previously thought to be essentially a question of macrocirculation.
      Today we start to see that microangiopathy is not only a consequence of large
      vessel diseases but can be the source of many pathologies in both cardiovascular
      and metabolic disorders, the best example -developed here- being the
      cardiometabolic syndrome or prediabetes. With very few exceptions, pentoxifylline
      and the antidiabetic metformin, no specific treatments have been developed for
      treating disorders at the microcirculatory level. Metformin has unique, intrinsic
      actions specifically at the level of terminal arterioles, which are completely
      independent of its antidiabetic effect. Other drugs are shortly described which
      have revealed a potential interest in this field. Our review aims at showing that
      microcirculation is entering a new era, starting with rapidly increasing
      knowledge of its intimate functioning and worth specific pharmacological
      developments.

PMID- 22480286
TI  - Dabigatran: a new chapter in anticoagulation.
AB  - For the last 60 years warfarin has been the cornerstone for chronic
      anticoagulation in prevention of ischemic strokes and systemic embolization.
      Warfarin therapy has several limitations including frequent monitoring and
      various food and significant drug interactions, which make it a less than ideal
      chronic oral anticoagulant. The continued search for safe, effective, medications
      with predictable pharmacokinetic profiles has led to newer alternatives.
      Dabigatran is a potent reversible, competitive direct thrombin inhibitor which is
      available as the prodrug, Dabigatran etexilate. It was first approved in Europe
      and recently in October 2010, the US food and drug administration (FDA) has
      approved the use of this novel oral anticoagulation for prevention of stroke in
      those with non valvular atrial fibrillation. This review will cover the chemical
      structure, mechanism of action, pharmacokinetic profile, clinical trials, dosage,
      clinical implication and adverse effects of dabigatran.

PMID- 22480288
TI  - Influence of urea on tert-butyl alcohol aggregation in aqueous solutions.
AB  - Ternary solutions consisting of urea, tert-butyl alcohol (TBA), and water are
      investigated employing molecular dynamics simulations. The main purpose of the
      present paper is to investigate the effect of urea on TBA aggregation and by
      extension its influence on hydrophobic interactions. The aggregation of TBA can
      be detected from the concentration dependence of structural properties such as
      first-shell TBA-water coordination numbers and TBA-TBA hydrogen-bond numbers, as
      well as through changes in the translational diffusion coefficients of TBA. It is
      found that urea acts to delay the association of TBA to concentrations greater
      than those required to cause TBA aggregation in binary TBA-water systems. It is
      shown that urea acts through a direct mechanism, whereby it preferentially binds
      to TBA replacing water from the first coordination shell. TBA-urea hydrogen bonds
      can be as strong as, or stronger than, those of TBA-water, and urea binds to both
      the hydrophilic and hydrophobic moieties of TBA. Our observations are
      qualitatively consistent with experimental results for urea-TBA-water solutions
      and with recent simulation studies of urea's action as a protein denaturant. 

PMID- 22480287
TI  - A model study for constructing the DEF-benzoxocin ring system of menogaril and
      nogalamycin via a reductive Heck cyclization.
AB  - A novel reductive Heck cyclization approach was developed in order to construct a
      model DEF-benzoxocin ring system that is present in nogalamycin, menogaril, and
      related anthracycline antitumor antibiotics.

PMID- 22480289
TI  - Nucleophilic substitution: a charge density perspective.
AB  - A general description of nucleophilic reactions is developed using bond bundles,
      an extension of the quantum theory of atoms in molecules, allowing novel
      activating groups to be predicted for aromatic rings. Reactivity is found to be
      related to both the shape of the bond bundle between the substrate and leaving
      group and the presence of nonbonding regions. Closed bond bundles are shown to be
      more reactive than open ones, while nonbonding regions also increase reactivity.
      The advantage of this approach is that it can be employed to investigate all
      molecular and solid-state systems. By way of example I use this model to
      rationalize two anomalously reactive systems: strained heterocyclic rings and
      sulfide-activated aromatic rings.

PMID- 22480291
TI  - RP-HPLC method for the simultaneous quantitation of boeravinone E and boeravinone
      B in Boerhaavia diffusa extract and its formulation.
AB  - A high-performance liquid chromatography method was developed and validated for
      the simultaneous quantitation of two major rotenoids, boeravinone E and
      boeravinone B, in Boerhaavia diffusa extract and its formulation. Chromatographic
      separation was carried out on an Inertsil ODS-3 column by using gradient mobile
      phase containing 0.1% v/v orthophosphoric acid in water and acetonitrile. The
      detection was carried out at 276 nm. The method was validated for specificity,
      precision, accuracy and robustness. The linearity (r(2) = 0.9989 and 0.9991) was
      found to be in the range of 7.26-35.75 ug mL(-1) and 2.20-11.00 ug mL(-1) for
      boeravinone E and B, respectively. The percent recovery observed from the extract
      sample was 95.22-95.83.

PMID- 22480290
TI  - Biochemical and structural characterization of germicidin synthase: analysis of a
      type III polyketide synthase that employs acyl-ACP as a starter unit donor.
AB  - Germicidin synthase (Gcs) from Streptomyces coelicolor is a type III polyketide
      synthase (PKS) with broad substrate flexibility for acyl groups linked through a
      thioester bond to either coenzyme A (CoA) or acyl carrier protein (ACP).
      Germicidin synthesis was reconstituted in vitro by coupling Gcs with fatty acid
      biosynthesis. Since Gcs has broad substrate flexibility, we directly compared the
      kinetic properties of Gcs with both acyl-ACP and acyl-CoA. The catalytic
      efficiency of Gcs for acyl-ACP was 10-fold higher than for acyl-CoA, suggesting a
      strong preference toward carrier protein starter unit transfer. The 2.9 A
      germicidin synthase crystal structure revealed canonical type III PKS
      architecture along with an unusual helical bundle of unknown function that
      appears to extend the dimerization interface. A pair of arginine residues
      adjacent to the active site affect catalytic activity but not ACP binding. This
      investigation provides new and surprising information about the interactions
      between type III PKSs and ACPs that will facilitate the construction of
      engineered systems for production of novel polyketides.

PMID- 22480292
TI  - Two acentric mononuclear molecular complexes with unusual magnetic and
      ferroelectric properties.
AB  - Two acentric, i.e., noncentrosymmetric, mononuclear complexes, Co(5-ATZ)(4)Cl(2),
      1, and Cu(5-ATZ)(4)Cl(2), 2, where 5-ATZ is the monodentate 5-amino-1-H-tetrazole
      ligand, have been prepared and characterized. Both complexes crystallize in the
      tetragonal system with the P4nc space group, a member of the polar
      noncentrosymmetric 4mm class, and thus both 1 and 2 can exhibit ferroelectric and
      nonlinear optical properties. Magnetic studies indicate that 1 is a paramagnetic
      high-spin cobalt(II) complex with a rather extensive spin-orbit coupling, modeled
      as a zero-field splitting parameter, D, of +/-91(3) cm(-1) and with very weak
      long-range antiferromagnetic exchange interactions. Direct current (dc) and ac
      magnetic studies indicate that 2 is a paramagnetic copper(II) complex that
      exhibits weak ferromagnetic exchange interactions below 15 K. Both 1 and 2
      exhibit ferroelectric hysteresis loops at room temperature with remanent
      polarizations of 0.015 MUC/cm(2) and coercive electric fields of 5.5 and 5.7
      kV/cm, respectively.

PMID- 22480293
TI  - No effect of creatine supplementation on oxidative stress and cardiovascular
      parameters in spontaneously hypertensive rats.
AB  - BACKGROUND: Exacerbated oxidative stress is thought to be a mediator of arterial
      hypertension. It has been postulated that creatine (Cr) could act as an
      antioxidant agent preventing increased oxidative stress. The aim of this study
      was to investigate the effects of nine weeks of Cr or placebo supplementation on
      oxidative stress and cardiovascular parameters in spontaneously hypertensive rats
      (SHR). FINDINGS: Lipid hydroperoxidation, one important oxidative stress marker,
      remained unchanged in the coronary artery (Cr: 12.6 +/- 1.5 vs. Pl: 12.2 +/- 1.7
      nmol.mg-1; p = 0.87), heart (Cr: 11.5 +/- 1.8 vs. Pl: 14.6 +/- 1.1 nmol.mg-1; p =
      0.15), plasma (Cr: 67.7 +/- 9.1 vs. Pl: 56.0 +/- 3.2 nmol.mg-1; p = 0.19),
      plantaris (Cr: 10.0 +/- 0.8 vs. Pl: 9.0 +/- 0.8 nmol.mg-1; p = 0.40), and EDL
      muscle (Cr: 14.9 +/- 1.4 vs. Pl: 17.2 +/- 1.5 nmol.mg-1; p = 0.30). Additionally,
      Cr supplementation affected neither arterial blood pressure nor heart structure
      in SHR (p > 0.05). CONCLUSIONS: Using a well-known experimental model of systemic
      arterial hypertension, this study did not confirm the possible therapeutic
      effects of Cr supplementation on oxidative stress and cardiovascular dysfunction
      associated with arterial hypertension.

PMID- 22480294
TI  - Formulation and characterization of liquid crystal systems containing azelaic
      acid for topical delivery.
AB  - PURPOSE: The aim of this study is to prepare and characterize azelaic acid (AzA)
      containing liquid crystal (LC) drug delivery systems for topical use. METHODS:
      Two ternary phase diagrams, containing liquid paraffin as the oil component and a
      mixture of two nonionic surfactants (Brij 721P and Brij 72), were constructed.
      Formulations chosen from the phase diagrams were characterized by polarized light
      microscopy, rheological analyses, differential scanning calorimetry (DSC), and
      small angle x-ray scattering spectroscopy. RESULTS: Polarized light microscopy
      proved that except the oil/water emulsion (O/W E), other formulations showed
      lamellar LC structure. In vitro release studies indicated that the fastest
      release was achieved by the Lamellar LC (LLC) and O/W E systems, whereas slower
      release was obtained from the emulsion containing lamellar LC (E-LLC) and
      distorted lamellar LC (D-LLC) systems. Results of rheological measurements both
      supported the results of in vitro release studies and showed that the emulsion
      containing the LC (E-LLC) system had the most stable structure. The formulations
      and their effect on stratum corneum (SC) were evaluated by DSC studies. The
      lamellar LC (LLC), emulsion containing lamellar liquid crystal (E-LLC), and O/W E
      formulations had an effect on both lipid and protein components of SC, whereas
      distorted lamellar liquid crystal (D-LLC) system had an effect on only the lipid
      components of SC. CONCLUSIONS: LLC systems could be considered promising for the
      topical delivery of AzA.

PMID- 22480295
TI  - Phage endolysins with broad antimicrobial activity against Enterococcus faecalis
      clinical strains.
AB  - Increasing antibiotic resistance of bacterial pathogens has drawn the attention
      to the potential use of bacteriophage endolysins as alternative antibacterial
      agents. Here we have identified, characterized, and studied the lytic potential
      of two endolysins, Lys168 and Lys170, from phages infecting Enterococcus
      faecalis. Lys168 and Lys170 belong to the cysteine, histidine-dependent
      amidohydrolases/peptidases (CHAP) and amidase-2 protein families, respectively.
      Lys168 is quite a unique enterococcal phage endolysin. It shares 95% amino acidic
      identity with the endolysin of Staphylococcus aureus phage SAP6, which in turn is
      distantly related to all known CHAP endolysins of S. aureus phages. Lys170 seems
      to be a natural chimera assembling catalytic and cell-wall-binding domains of
      different origin. Both endolysins showed a clear preference to act against E.
      faecalis and they were able to lyse a high proportion of clinical isolates of
      this species. Specifically, Lys168 and Lys170 lysed more than 70% and 90% of the
      tested isolates, respectively, which included a panel of diverse and typed
      strains representative of highly prevalent clonal complexes. Lys170 was active
      against all tested E. faecalis VRE strains. The quasi specificity toward E.
      faecalis is discussed considering the nature of the enzymes' functional domains
      and the structure of the cell wall peptidoglycan.

PMID- 22480296
TI  - Disruption of functional brain networks in Alzheimer's disease: what can we learn
      from graph spectral analysis of resting-state magnetoencephalography?
AB  - In Alzheimer's disease (AD), structural and functional brain network organization
      is disturbed. However, many of the present network analysis measures require a
      priori assumptions and methodological choices that influence outcomes and
      interpretations. Graph spectral analysis (GSA) is a more direct algebraic method
      that describes network properties, which might lead to more reliable results. In
      this study, GSA was applied to magnetoencephalography (MEG) data to explore
      functional network integrity in AD. Sensor-level resting-state MEG was performed
      in 18 Alzheimer patients (age 67 +/- 9, 6 women) and 18 healthy controls (age 66
      +/- 9, 11 women). Weighted, undirected graphs were constructed based on
      functional connectivity analysis using the Synchronization likelihood, and GSA
      was performed with a focus on network connectivity, synchronizability, and node
      centrality. The main outcomes were a global loss of network connectivity and
      altered synchronizability in most frequency bands. Eigenvector centrality mapping
      confirmed the hub status of the parietal areas, and demonstrated a low centrality
      of the left temporal region in the theta band in AD patients that was strongly
      related to the mini mental state examination (global cognitive function test)
      score (r=0.67, p=0.001). Summarizing, GSA is a theoretically solid approach that
      is able to detect the disruption of functional network topology in AD. In
      addition to the previously reported overall connectivity losses and parietal area
      hub status, impaired network synchronizability and a clinically relevant left
      temporal centrality loss were found in AD patients. Our findings imply that GSA
      is valuable for the purpose of studying altered brain network topology and
      dynamics in AD.

PMID- 22480297
TI  - Aroma chemical composition of red wines from different price categories and its
      relationship to quality.
AB  - The aroma chemical composition of three sets of Spanish red wines belonging to
      three different price categories was studied by using an array of gas
      chromatographic methods. Significant differences were found in the levels of 72
      aroma compounds. Expensive wines are richest in wood-related compounds, ethyl
      phenols, cysteinil-derived mercaptans, volatile sulfur compounds, ethyl esters of
      branched acids, methional, and phenylacetaldehyde and are poorest in linear and
      branched fatty acids, fusel alcohols, terpenols, norisoprenoids, fusel alcohol
      acetates, and ethyl esters of the linear fatty acids; inexpensive wines show
      exactly the opposite profile, being richest in E-2-nonenal, E-2-hexenal, Z-3
      hexenol, acetoin, and ethyl lactate. Satisfactory models relating quality to
      odorant composition could be built exclusively for expensive and medium-price
      wines but not for the lower-price sample set in which in-mouth attributes had to
      be included. The models for quality reveal a common structure, but they are
      characteristic of a given sample set.

PMID- 22480298
TI  - The winds of change.

PMID- 22480300
TI  - A multi-sensor monitoring system of human physiology and daily activities.
AB  - OBJECTIVE: To present the design and pilot test results of a continuous multi
      sensor monitoring system of real-world physiological conditions and daily life
      (activities, travel, exercise, and food consumption), culminating in a Web-based
      graphical decision-support interface. MATERIALS AND METHODS: The system includes
      a set of wearable sensors wirelessly connected to a "smartphone" with a
      continuously running software application that compresses and transmits the data
      to a central server. Sensors include a Global Positioning System (GPS) receiver,
      electrocardiogram (ECG), three-axis accelerometer, and continuous blood glucose
      monitor. A food/medicine diary and prompted recall activity diary were also used.
      The pilot test involved 40 type 2 diabetic patients monitored over a 72-h period.
      RESULTS: All but three subjects were successfully monitored for the full study
      period. Smartphones proved to be an effective hub for managing multiple streams
      of data but required attention to data compression and battery consumption
      issues. ECG, accelerometer, and blood glucose devices performed adequately as
      long as subjects wore them. GPS tracking for a full day was feasible, although
      significant efforts are needed to impute missing data. Activity detection
      algorithms were successful in identifying activities and trip modes but could
      benefit by incorporating accelerometer data. The prompted recall diary was an
      effective tool for augmenting algorithm results, although subjects reported some
      difficulties with it. The food and medicine diary was completed fully, although
      end times and medicine dosages were occasionally missing. CONCLUSIONS: The unique
      combination of sensors holds promise for increasing accuracy and reducing burden
      associated with collecting individual-level activity and physiological data under
      real-world conditions, but significant data processing issues remain. Such data
      will provide new opportunities to explore the impacts of human geography and
      daily lifestyle on health at a fine spatial/temporal scale.

PMID- 22480301
TI  - E-health and healthcare enterprise information system leveraging service-oriented
      architecture.
AB  - OBJECTIVE: To present the successful experiences of an integrated, collaborative,
      distributed, large-scale enterprise healthcare information system over a wired
      and wireless infrastructure in National Taiwan University Hospital (NTUH). In
      order to smoothly and sequentially transfer from the complex relations among the
      old (legacy) systems to the new-generation enterprise healthcare information
      system, we adopted the multitier framework based on service-oriented architecture
      to integrate the heterogeneous systems as well as to interoperate among many
      other components and multiple databases. We also present mechanisms of a logical
      layer reusability approach and data (message) exchange flow via Health Level 7
      (HL7) middleware, DICOM standard, and the Integrating the Healthcare Enterprise
      workflow. The architecture and protocols of the NTUH enterprise healthcare
      information system, especially in the Inpatient Information System (IIS), are
      discussed in detail. IMPLEMENTATION: The NTUH Inpatient Healthcare Information
      System is designed and deployed on service-oriented architecture middleware
      frameworks. The mechanisms of integration as well as interoperability among the
      components and the multiple databases apply the HL7 standards for data exchanges,
      which are embedded in XML formats, and Microsoft .NET Web services to integrate
      heterogeneous platforms. MEASUREMENTS: The preliminary performance of the current
      operation IIS is evaluated and analyzed to verify the efficiency and
      effectiveness of the designed architecture; it shows reliability and robustness
      in the highly demanding traffic environment of NTUH. CONCLUSIONS: The newly
      developed NTUH IIS provides an open and flexible environment not only to share
      medical information easily among other branch hospitals, but also to reduce the
      cost of maintenance. The HL7 message standard is widely adopted to cover all data
      exchanges in the system. All services are independent modules that enable the
      system to be deployed and configured to the highest degree of flexibility.
      Furthermore, we can conclude that the multitier Inpatient Healthcare Information
      System has been designed successfully and in a collaborative manner, based on the
      index of performance evaluations, central processing unit, and memory
      utilizations.

PMID- 22480302
TI  - Comprehensive predictions of target proteins based on protein-chemical
      interaction using virtual screening and experimental verifications.
AB  - BACKGROUND: Identification of the target proteins of bioactive compounds is
      critical for elucidating the mode of action; however, target identification has
      been difficult in general, mostly due to the low sensitivity of detection using
      affinity chromatography followed by CBB staining and MS/MS analysis. RESULTS: We
      applied our protocol of predicting target proteins combining in silico screening
      and experimental verification for incednine, which inhibits the anti-apoptotic
      function of Bcl-xL by an unknown mechanism. One hundred eighty-two target protein
      candidates were computationally predicted to bind to incednine by the statistical
      prediction method, and the predictions were verified by in vitro binding of
      incednine to seven proteins, whose expression can be confirmed in our cell
      system.As a result, 40% accuracy of the computational predictions was achieved
      successfully, and we newly found 3 incednine-binding proteins. CONCLUSIONS: This
      study revealed that our proposed protocol of predicting target protein combining
      in silico screening and experimental verification is useful, and provides new
      insight into a strategy for identifying target proteins of small molecules.

PMID- 22480303
TI  - Primary pleural leiomyosarcoma with rapid progression and fatal outcome: a case
      report.
AB  - INTRODUCTION: Leiomyosarcomas are neoplasms of smooth muscles that most commonly
      arise from the uterus, gastrointestinal tract, or soft tissue. Primary pleural
      leiomyosarcoma is extremely rare. To the best of our knowledge, only nine cases
      have been published to date. Because of the rarity of pleural leiomyosarcoma and
      its similarity (clinical and histological) to other pleural neoplasms,
      particularly sarcomatous mesothelioma, diagnosis is often difficult. CASE
      PRESENTATION: A 58-year-old North African man was admitted with complaints of
      dyspnea and chest pain to our hospital. Chest computed tomography revealed right
      pleural effusion and pleural thickening. A transthoracic needle biopsy yielded a
      diagnosis of leiomyosarcoma, and tumor cells were strongly and uniformly positive
      for vimentin, a smooth muscle actin at immunohistochemical analysis. A general
      examination did not show any metastatic lesions in other areas. One month after
      diagnosis, the tumor grew rapidly, with pulmonary invasion, and therefore he was
      treated only by palliative care. He died from respiratory failure one month
      later. Because no organ of origin of the leiomyosarcoma, other than the pleura,
      was detected, this case was diagnosed as a primary pleural leiomyosarcoma.
      CONCLUSIONS: Although leiomyosarcoma originating from the pleura is rare, this
      entity is increasingly described. The purpose of presenting this case report is
      to raise awareness among clinicians to consider this clinical entity as a
      differential diagnosis when a pleural mass is identified.

PMID- 22480304
TI  - Pain in the three spinal regions: the same disorder? Data from a population-based
      sample of 34,902 Danish adults.
AB  - BACKGROUND: Studies of back pain are typically based on the assumption that
      symptoms from different parts of the spine are distinctive entities. Recently,
      however, the assumption that back pain is a site-specific disorder has been
      challenged, suggesting that localized back pain should be seen as part of a
      general musculoskeletal syndrome. OBJECTIVES: To describe and compare the
      patterns of reporting of pain and consequences of pain in the three spinal
      regions. METHODS: In all, 34,902 (74%) twin individuals representative of the
      general Danish population, aged 20 to 71, participated in a cross-sectional
      nation-wide survey. Identical questions from the Standardised Nordic
      Questionnaire for each of the three spinal regions were used for lumbar, mid-back
      and neck pain respectively: Pain past year, pain ever, radiating pain, and
      consequences of back pain (care-seeking, reduced physical activities, sick-leave,
      change of work/work duties and disability pension). The relative prevalence
      estimates of these variables were compared for the three spinal regions. RESULTS:
      The relative proportions of individuals with pain ever, who also reported to have
      had pain in the past year varied between 75% and 80%, for the three spinal
      regions. The proportions of individuals with pain in the past year and for
      various pain durations were also very similar. Regardless if pain was reported in
      the lumbar, thoracic or cervical regions, the proportions of individuals
      reporting radiating pain were equally large. The relative number of consequences
      was the same across the spinal regions, as were the relative proportions of each
      these consequences. However, low back pain resulted more often in some kind of
      consequence compared to the consequences of pain in the neck and mid back.
      CONCLUSIONS: Back pain and its consequences share many characteristics and may,
      at least in a general population, be regarded as the same condition regardless of
      where the pain happens to manifest itself. However, because some exceptions were
      noted for the lumbar spine, separate entities for a smaller group of individuals
      with back pain cannot be ruled out.

PMID- 22480305
TI  - Separation of antigens and antibodies by immunoaffinity chromatography.
AB  - CONTEXT: Affinity chromatography is an efficient antibody, antigen and protein
      separation method based on the interaction between specific immobilized ligands
      and target antibody, antigen, and so on. Populations of available ligands can be
      used to separate antibodies or their Fab fragments. Similarly, antigens can be
      isolated by immunoaffinity chromatography (IAC) on immobilized antibodies of low
      affinity. OBJECTIVE: This review describes the advantages, the applications, as
      well as the drawbacks, of IAC in the separation and purification of antibodies
      and antigens. METHODS: The present review discussed all types of purification and
      isolation of antibodies and antigens by IAC, including purification of antibodies
      using immobilized and synthetic mimic proteins A, G and L; isolation of Fab
      fragments of antibodies; separation of antibodies against different antigen
      forms; isolation of antigens by immobilized antibodies and so on. These methods
      come from over 60 references compiled from all major databases. RESULTS:
      Purification of antigens with antibodies should choose low-affinity antibodies to
      avoid denaturation of most proteins. Concern for cost and safety, prompted
      research activities focused on novel synthetic ligands with improved properties
      such as lower cost, avoidance of the risk of contamination associated with
      natural ligands of human or animal origin to isolate antibodies and antigens.
      CONCLUSION: It is anticipated that the improvements of IAC will have impact not
      only on large-scale production of antibodies but also on the generation of new
      affinity-based methods for the increasing number of proteins and antibody
      derivatives available by protein engineering and the proteomics revolution.

PMID- 22480306
TI  - Metabolism and distribution of benzo[a]pyrene-7,8-dione (B[a]P-7,8-dione) in
      human lung cells by liquid chromatography tandem mass spectrometry: detection of
      an adenine B[a]P-7,8-dione adduct.
AB  - Benzo[a]pyrene-7,8-dione (B[a]P-7,8-dione) is produced in human lung cells by the
      oxidation of (+/-)-B[a]P-7,8-trans-dihydrodiol, which is catalyzed by aldo-keto
      reductases (AKRs). However, information relevant to the cell-based metabolism of
      B[a]P-7,8-dione is lacking. We studied the metabolic fate of 2 MUM 1,3-[(3)H(2)]
      B[a]P-7,8-dione in human lung adenocarcinoma A549 cells, human bronchoalveolar
      H358 cells, and immortalized human bronchial epithelial HBEC-KT cells. In these
      three cell lines, 1,3-[(3)H(2)]-B[a]P-7,8-dione was rapidly consumed, and
      radioactivity was distributed between the organic and aqueous phase of ethyl
      acetate-extracted media, as well as in the cell lysate pellets. After
      acidification of the media, several metabolites of 1,3-[(3)H(2)]-B[a]P-7,8-dione
      were detected in the organic phase of the media by high performance liquid
      chromatography-ultraviolet-radioactivity monitoring (HPLC-UV-RAM). The structures
      of B[a]P-7,8-dione metabolites varied in the cell lines and were identified as
      B[a]P-7,8-dione conjugates with glutathione (GSH) and N-acetyl-l-cysteine (NAC),
      8-O-monomethylated-catechol, catechol monosulfate, and monoglucuronide, and
      monohydroxylated-B[a]P-7,8-dione by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). We also obtained evidence for the first time for the
      formation of an adenine adduct of B[a]P-7,8-dione. Among these metabolites, the
      identity of the GSH-B[a]P-7,8-dione and the NAC-B[a]P-7,8-dione was further
      validated by comparison to authentic synthesized standards. The pathways of B[a]P
      7,8-dione metabolism in the three human lung cell lines are formation of GSH and
      NAC conjugates, reduction to the catechol followed by phase II conjugation
      reactions leading to its detoxification, monohydroxylation, as well as formation
      of the adenine adduct.

PMID- 22480307
TI  - Homogeneity, modulus, and viscoelasticity of polyelectrolyte multilayers by
      nanoindentation: refining the buildup mechanism.
AB  - Atomic force microscopy, AFM, and nanoindentation of polyelectrolyte multilayers,
      PEMUs, made from poly(diallyldimethylammonium), PDADMA, and poly(styrene
      sulfonate), PSS, provided new insight into their surface morphology and growth
      mechanism. A strong odd/even alternation of surface modulus revealed greater
      extrinsic (counterion-balanced) charge compensation for fully hydrated
      multilayers ending in the polycation, PDADMA. These swings in modulus indicate a
      much more asymmetric layer-by-layer growth mechanism than previously proposed.
      Viscoelastic properties of the PEMU, which may contribute to cell response, were
      highlighted by variable indentation rates and minimized by extrapolating to zero
      indentation rate, at which point the surface and bulk equilibrium moduli were
      comparable. Variations in surface composition were probed at high resolution
      using force mapping, and the surface was found to be uniform, with no evidence of
      phase separation. AFM comparison of wet and dry films terminated with PSS and
      PDADMA revealed much greater swelling of the PDADMA-terminated PEMU by water,
      with collapse of surface roughness features in dry conditions. Dynamic and static
      contact angle measurements suggested less rearrangement for the glassy PSS
      surface.

PMID- 22480309
TI  - Mapping structural perturbations of water in ionic solutions.
AB  - The structure of water in sodium halide aqueous solutions at different
      concentrations is studied through molecular dynamics. Emphasis is placed on the
      extent of ionic-induced changes in the water structure, and the concept of
      kosmotropes/chaotropes is probed, in terms of perturbations to the tetrahedral H
      bond network of water. The results show that at low salt concentrations, the
      halide anions slightly increase the tetrahedrality of the H-bond network of water
      in the anionic second hydration shell and I(-) is found to be the strongest
      kosmotrope, contrary to its structure breaker reputation. The sodium cation in
      turn induces a significant loss of tetrahedrality in the second cationic
      hydration shell. At higher concentrations, the dominant disruptive effect of
      Na(+) cancels the anionic effects, even in the anionic second hydration shell.
      According to a kosmotropes/chaotropes classification of ions, based on the
      tetrahedrality of the H-bond network of water, halide anions are therefore weak
      kosmotropes, while Na(+) is a strong chaotrope. However, if this classification
      is applied to the salts, rather than to the ions, all of the sodium halides are
      classified as structure breakers even at low concentrations. Further, the effect
      of pressure on the tetrahedrality of the H-bond network of water is found to be
      similar to the average effect of the dissolved salts. The present results
      indicate that the classification of ions in kosmotropes/chaotropes in terms of
      long-range perturbations to the tetrahedral H-bond network of water is not
      correlated to the position of the ions in the respective Hofmeister series.

PMID- 22480308
TI  - Riluzole neuroprotection in a Parkinson's disease model involves suppression of
      reactive astrocytosis but not GLT-1 regulation.
AB  - BACKGROUND: Riluzole is a neuroprotective drug used in the treatment of motor
      neurone disease. Recent evidence suggests that riluzole can up-regulate the
      expression and activity of the astrocyte glutamate transporter, GLT-1. Given that
      regulation of glutamate transport is predicted to be neuroprotective in
      Parkinson's disease, we tested the effect of riluzole in parkinsonian rats which
      had received a unilateral 6-hydroxydopamine injection into the median forebrain
      bundle. RESULTS: Rats were treated with intraperitoneal riluzole (4 mg/kg or 8
      mg/kg), 1 hour before the lesion then once daily for seven days. Riluzole
      produced a modest but significant attenuation of dopamine neurone degeneration,
      assessed by suppression of amphetamine-induced rotations, preservation of
      tyrosine hydroxylase positive neuronal cell bodies in the substantia nigra pars
      compacta and attenuation of striatal tyrosine hydroxylase protein loss. Seven
      days after 6-hydroxydopamine lesion, reactive astrocytosis was observed in the
      striatum, as determined by increases in expression of glial fibrillary acidic
      protein, however the glutamate transporter, GLT-1, which is also expressed in
      astrocytes was not regulated by the lesion. CONCLUSIONS: The results confirm that
      riluzole is a neuroprotective agent in a rodent model of parkinson's disease.
      Riluzole administration did not regulate GLT-1 levels but significantly reduced
      GFAP levels, in the lesioned striatum. Riluzole suppression of reactive
      astrocytosis is an intriguing finding which might contribute to the
      neuroprotective effects of this drug.

PMID- 22480310
TI  - Resveratrol nanoparticle system improves dissolution properties and enhances the
      hepatoprotective effect of resveratrol through antioxidant and anti-inflammatory
      pathways.
AB  - Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is
      abundant in red wine and exerts numerous pharmacological effects, including
      hepatoprotection and cadioprotection. Unfortunately, RES is restricted in
      clinical application due to poor dissolution property and adsorption. In
      addition, red wine as a supplement for preventing disease is not recommended for
      patients with alcohol-related disorders. To address these limitations, we
      successfully developed a novel RES nanoparticle system (RESN) and demonstrated
      that RESN could circumvent the physicochemical drawbacks of raw RES with respect
      to dissolution, such as the reduction of particle size, amorphous transformation,
      and hydrogen-bond formation. In addition, we employed an animal model of CCl4
      induced hepatotoxicity to estimate the potential of the nanoparticle formulation
      to improve the hepatoprotective effect of orally administered RES. Our results
      demonstrated that RESN can diminish liver function markers (aspartate
      aminotransferase and alanine aminotransferase) by decreasing hepatocyte death due
      to CCl4-induced hepatotoxicity in rats, when compared with RES administration.
      The effect was achieved by reducing oxidative stress (decreased reactive oxygen
      species and lipid peroxidation) and lowering inflammatory cytokines (decreased
      tumor necrosis factor-alpha and interleukin 1beta) and protein expression
      (cyclooxygenase-2, inducible nitric oxide synthase, cytosolic phospholipase A2,
      and caspase-3). In conclusion, enhancement of the dissolution of RES through a
      nanoparticle engineering process can result in increased hepatoprotective effects
      mediated by antioxidant and anti-inflammatory activities. Consequently, we
      suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver
      diseases.

PMID- 22480311
TI  - Aromatic polyketide production in Cordyceps indigotica, an entomopathogenic
      fungus, induced by exposure to a histone deacetylase inhibitor.
AB  - Cultivation of Cordyceps indigotica, an entomopathogenic fungus, in the presence
      of suberoyl bis-hydroxamic acid (an HDAC inhibitor) greatly activated its
      polyketide synthesis apparatus to afford six novel aromatic polyketides,
      indigotides C-F (1-4), 13-hydroxyindigotide A (5), and 8-O-methylindigotide B
      (6). The structures of these compounds were determined by NMR spectroscopic
      analyses. Among the compounds, indigotides C-E (1-3) possessed unprecedented
      dimeric polyketide frameworks possibly generated via a [4 + 2] cycloaddition or
      Michael type reaction.

PMID- 22480312
TI  - Understanding ion sensing in Zn(II) porphyrins: spectroscopic and computational
      studies of nitrite/nitrate binding.
AB  - The development of effective sensor elements relies on the ability of a
      chromophore to bind an analyte selectively and then study the binding through
      changes in spectroscopic signals. In this report the ability of Zn(II)
      Tetraphenyl Porphyrin (ZnTPP) to selectively bind nitrite over nitrate ions is
      examined. The results of Benesi-Hildebrand analysis reveals that ZnTPP binds
      NO(2)(-) and NO(3)(-) ions with association constants of 739 +/- 70 M(-1) and 134
      +/- 15 M(-1), respectively. Interestingly, addition of a pyridine ligand to the
      fifth coordination site of the Zn(II) center enhances ion binding with the
      association constants increasing to 71,300 +/- 8,000 M(-1) and 18,900 +/- 3,000
      M(-1) for nitrite and nitrate, respectively. Density functional theory
      calculations suggest a binding mechanism through which Zn(II)-porphyrin
      interactions are disrupted by ligand and base coordination to Zn(II), with Zn(II)
      having more favorable overlap with nitrite orbitals, which are less delocalized
      than nitrate orbitals. Overall, these provide new insights into the ability to
      tune the affinity and selectivity of porphyrin based sensors utilizing electronic
      factors associated with the central Zn(II) ion.

PMID- 22480314
TI  - Potent gene silencing in vitro at physiological pH using chitosan polymers.
AB  - Among non-viral cationic polymers, biodegradable chitosan has during the last
      decade become an attractive carrier for small interference RNA (siRNA) delivery.
      Currently, degradation of macromolecules in the lysosomes is assumed to be a
      major barrier for effective siRNA transfection. Hence, transfection protocols are
      focused toward endosomal release mechanisms. In this work, we have tested 3 novel
      chitosan polymers and their siRNA delivery properties in vitro. To obtain
      efficient gene silencing of our model gene, S100A4, various transfection
      parameters were investigated, such as pH, nitrogen/phosphate ratio, photochemical
      internalization (PCI), media for complex formation, and cell lines. Our results
      showed that 2 linear chitosan polymers demonstrated excellent siRNA gene
      silencing, better than Lipofectamine 2000. The silencing effect was achieved
      without PCI treatment, under physiological pH, and with no observable reduction
      in cell viability.

PMID- 22480317
TI  - Oral gene delivery with cyclo-(D-Trp-Tyr) peptide nanotubes.
AB  - The feasibility of cyclo-(D-Trp-Tyr) peptide nanotubes (PNTs) as oral gene
      delivery carriers was investigated in nude mice with eight 40 MUg doses of pCMV
      lacZ in 2 days at 3 h intervals. The association between DNA and PNTs, the DNase
      I stability of PNTs-associated DNA, and in vitro permeability of DNA were
      estimated. The results showed that the cyclo-(D-Trp-Tyr) PNTs self-associated at
      concentrations above 0.01 mg/mL. Plasmid DNA associated with PNTs with a binding
      constant of 3.2 * 10(8) M(-1) calculated by a fluorescence quenching assay. PNTs
      were able to protect DNA from DNase I, acid, and bile digestion for 50 min, 60
      min, and 180 min, respectively. The in vitro duodenal apparent permeability
      coefficient of pCMV-lacZ calculated from a steady state flux was increased from
      49.2 +/- 21.6 * 10(-10) cm/s of naked DNA to 395.6 +/- 142.2 * 10(-10) cm/s of
      pCMV-lacZ/PNT formulation. The permeation of pCMV-lacZ formulated with PNTs was
      found in an energy-dependent process. Furthermore, beta-galatosidase (beta-Gal)
      activity in tissues was quantitatively assessed using chlorophenol red-beta-D
      galactopyranoside (CPRG) and was significantly increased by 41% in the kidneys at
      48 h and by 49, 63, and 46% in the stomach, duodenum, and liver, respectively, at
      72 h after the first dose of oral delivery of pCMV-lacZ/PNT formulation. The
      organs with beta-Gal activity were confirmed for the presence of pCMV-lacZ DNA
      with Southern blotting analysis and intracellular tracing the TM-rhodamine
      labeled DNA and the presence of mRNA by reverse transcription-real time
      quantitative PCR (RT-qPCR). Another plasmid (pCMV-hRluc) encoding Renilla
      reniformis luciferase was used to confirm the results. An increased hRluc mRNA
      and luciferase in stomach, duodenum, liver, and kidney were detected by RT-qPCR,
      ex vivo bioluminescence imaging, luciferase activity quantification, and
      immunostaining, respectively.

PMID- 22480315
TI  - The interaction of telomeric DNA and C-myc22 G-quadruplex with 11 natural
      alkaloids.
AB  - Telomeric DNA and C-myc22 are DNA G-quadruplex (G4)-forming sequences associated
      with tumorigenesis. Ligands that can facilitate the formation and increase the
      stabilization of G4 can halt tumor cell proliferation and have been regarded as
      potential anti-cancer drugs. In the present study, we have investigated the
      interaction of 11 natural alkaloids with G4 formed by telomeric DNA and C-myc22
      sequences. Our results indicated that sanguinarine (San), palmatine (Pal), and
      berberine (Beb) of the first series (S1) can induce the formation of G4 as well
      as increase the stabilization ability. Daurisoline (S2-1), O-methyldauricine (S2
      2), O-diacetyldaurisoline (S2-3), daurinoline (S2-4), dauricinoline (S2-5), N,N'
      dimethyldauricine iodide (S2-6), and N,N'-dimethyldaurisoline iodide (S2-7) of
      the second series (S2) showed similar stabilization ability. We found that
      unsaturated ring C, N(+) positively charged centers, and conjugated aromatic
      rings are key factors to increase the stabilization ability of S1, and we gave
      some advice on structure modification to S2 through structure-activity study.
      Besides, we found San and Pal to be cell cycle blocker in G(1). San was
      speculated to bind to G4 through intercalation or end stacking.

PMID- 22480318
TI  - Determination of lymphotoxin-alpha levels in patients with psoriatic arthritis
      undergoing etanercept treatment.
AB  - Tumor necrosis factor (TNF)-alpha plays a central role in psoriatic arthritis
      (PsA). A subgroup of patients with PsA do not respond to anti-TNF-alpha
      antibodies but respond to TNF receptor p75-Fc IgG fusion protein (etanercept),
      which also neutralizes lymphotoxin (LT)-alpha. It has been suggested that LT
      alpha might be involved in the development of the disease. We determined LT-alpha
      serum levels in 15 PsA patients before (T0) and after 3, 6, 9, and 12 months of
      etanercept therapy (T3, T6, T9, and T12, respectively) and correlated them with
      their response to treatment. Bath Ankylosing Spondylitis Disease Activity Index,
      Psoriasis Area Severity Index, Disease Activity Score (DAS28), erythrocyte
      sedimentation rate (ESR), and C reactive protein (CRP) levels were assessed at
      the same time points. All patients showed a clinical response at T6, which
      persisted up to T12; ESR and CRP mean levels significantly decreased at T3 and
      remained within the normal range up to T12. LT-alpha levels significantly
      increased from T3 to T6 and returned to baseline levels at T12. Therefore, the LT
      alpha serum levels do not seem to correlate with clinical and laboratory
      parameters of the response to etanercept in PsA patients. Further studies are
      required to better define the role of LT-alpha and LT-alpha blockade by
      etanercept in PsA patients.

PMID- 22480319
TI  - Impact of safety-related regulatory action on clinical practice: a systematic
      review.
AB  - BACKGROUND: After market approval, new serious safety issues are regularly
      identified for drugs that lead to regulatory action to inform healthcare
      professionals. However, the effectiveness of these safety-related regulatory
      actions is under question. We currently lack a comprehensive overview of the
      effects of these drug safety warnings on clinical practice to resolve the debate
      about their effectiveness. OBJECTIVE: The aim of this systematic review is to
      provide an overview of studies that assessed the impact of safety warnings. STUDY
      SELECTION: A systematic search was performed for articles assessing the impact of
      Direct Healthcare Professional Communications or 'Dear Doctor' letters, Black Box
      Warnings and Public Health Advisories on clinical behaviour published between
      January 1996 and January 2010. The following variables were extracted:
      publication year, country, name of the drug, safety issue, specific safety
      warning (Direct Healthcare Professional Communication/Black Box Warning/Public
      Health Advisory), effect (intended/unintended) of the safety warning, outcome
      measure and study design. Papers were checked for several quality aspects. Study
      data were summarized using descriptive analyses. RESULTS: A total of 50 articles
      were identified. Two articles assessed two different drugs and were therefore
      counted twice (n = 52). Thirty-three articles described the impact of safety
      warnings issued for three drugs and drug groups, i.e. third-generation oral
      contraceptives, cisapride and selective serotonin reuptake inhibitors. The
      remaining 19 articles described a broad variety of 14 drugs and drug groups.
      Twenty-five studies applied an interrupted time series design, 23 a controlled or
      uncontrolled before/after design, and four articles applied both. None of the
      articles could rule out the influence of confounding factors. The intended
      effects were reported in 18 (72%) of the 25 before/after analyses, whereas only
      11 (41%) of the 27 interrupted time series analyses reported an impact. Only two
      (8%) of the before/after analyses against 11 (41%) of the interrupted time series
      analyses reported mixed impacts. When unintended effects were assessed in case of
      selective serotonin reuptake inhibitors and third-generation oral contraceptives,
      these were almost always present: in 19 of 22 and 4 of 5 articles, respectively.
      Our review shows that safety-related regulatory action can have some impact on
      clinical practice but firm conclusions are difficult to draw. Evidence is
      primarily based on three drugs and drug groups. Almost half of the studies had
      inadequate before/after designs and the heterogeneity in analyses and outcome
      measures hampered the reporting of overall effect sizes. Studies with adequate
      interrupted time series design reported a more mixed impact of safety warnings
      than before/after studies. Furthermore, this review shows the relevance of
      considering not only the intended but also the unintended effects of safety
      warnings. CONCLUSIONS: There is a clear need for further research with
      appropriate study designs and statistical analyses, with more attention to
      confounding factors such as media coverage, to understand the impact of safety
      related regulatory action.

PMID- 22480320
TI  - Adapting test timing to the sleep-wake schedule: effects on diurnal
      neurobehavioral performance changes in young evening and older morning
      chronotypes.
AB  - The synchrony effect refers to the beneficial impact of temporal matching between
      the timing of cognitive task administration and preferred time-of-day for diurnal
      activity. Aging is often associated with an advance in sleep-wake timing and
      concomitant optimal performance levels in the morning. In contrast, young adults
      often perform better in the evening hours. So far, the synchrony effect has been
      tested at fixed clock times, neglecting the individual's sleep-wake schedule and
      thus introducing confounds, such as differences in accumulated sleep pressure or
      circadian phase, which may exacerbate synchrony effects. To probe this
      hypothesis, the authors tested older morning and young evening chronotypes with a
      psychomotor vigilance and a Stroop paradigm once at fixed morning and evening
      hours and once adapting testing time to their preferred sleep-wake schedule in a
      within-subject design. The authors observe a persistence of synchrony effects for
      overall median reaction times during a psychomotor vigilance task, even when
      testing time is adapted to the specific individual's sleep-wake schedule.
      However, data analysis also indicates that time-of-day modulations are weakened
      under those conditions for incongruent trials on Stroop performance and the
      slowest reaction times on the psychomotor vigilance task. The latter result
      suggests that the classically observed synchrony effect may be partially mediated
      by a series of parameters, such as differences in socio-professional timing
      constraints, the amount of accumulated sleep need, or circadian phase, all
      leading to differential arousal levels at testing.

PMID- 22480321
TI  - Antioxidant and antiproliferative activity of Hypericum hircinum L. subsp. majus
      (Aiton) N. Robson essential oil.
AB  - This study was undertaken to assess the antioxidant and antiproliferative
      potential of the essential oil of Hypericum hircinum L. subsp. majus (Aiton) N.
      Robson. Analysis of the oil composition revealed that sesquiterpene hydrocarbons
      (69.3%) dominate, cis-beta-guaiene, delta-selinene and (E)-caryophyllene being
      the most representative. Significant values of antioxidant activity were found
      using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging assays. The
      essential oil revealed antiproliferative activity as evaluated on human
      glioblastoma (T98G), human prostatic adenocarcinoma (PC3), human squamous
      carcinoma (A431) and mouse melanoma (B16-F1) tumour cell lines by MTT assay.

PMID- 22480322
TI  - Psoromic acid is a selective and covalent Rab-prenylation inhibitor targeting
      autoinhibited RabGGTase.
AB  - Post-translational attachment of geranylgeranyl isoprenoids to Rab GTPases, the
      key organizers of intracellular vesicular transport, is essential for their
      function. Rab geranylgeranyl transferase (RabGGTase) is responsible for
      prenylation of Rab proteins. Recently, RabGGTase inhibitors have been proposed to
      be potential therapeutics for treatment of cancer and osteoporosis. However, the
      development of RabGGTase selective inhibitors is complicated by its structural
      and functional similarity to other protein prenyltransferases. Herein we report
      identification of the natural product psoromic acid (PA) that potently and
      selectively inhibits RabGGTase with an IC(50) of 1.3 MUM. Structure-activity
      relationship analysis suggested a minimal structure involving the depsidone core
      with a 3-hydroxyl and 4-aldehyde motif for binding to RabGGTase. Analysis of the
      crystal structure of the RabGGTase:PA complex revealed that PA forms largely
      hydrophobic interactions with the isoprenoid binding site of RabGGTase and that
      it attaches covalently to the N-terminus of the alpha subunit. We found that in
      contrast to other protein prenyltransferases, RabGGTase is autoinhibited through
      N-terminal (alpha)His2 coordination with the catalytic zinc ion. Mutation of
      (alpha)His dramatically enhances the reaction rate, indicating that the activity
      of RabGGTase is likely regulated in vivo. The covalent binding of PA to the N
      terminus of the RabGGTase alpha subunit seems to potentiate its interaction with
      the active site and explains the selectivity of PA for RabGGTase. Therefore,
      psoromic acid provides a new starting point for the development of selective
      RabGGTase inhibitors.

PMID- 22480323
TI  - Chirped InGaAs quantum dot molecules for broadband applications.
AB  - Lateral InGaAs quantum dot molecules (QDMs) formed by partial-cap and regrowth
      technique exhibit two ground-state (GS) peaks controllable via the thicknesses of
      InAs seed quantum dots (x), GaAs cap (y), and InAs regrowth (z). By adjusting
      x/y/z in a stacked QDM bilayer, the GS peaks from the two layers can be offset to
      straddle, stagger, or join up with each other, resulting in multi-GS or broadband
      spectra. A non-optimized QDM bilayer with a 170-meV full-width at half-maximum is
      demonstrated. The temperature dependencies of the emission peak energies and
      intensities from the chirped QDM bilayers are well explained by Varshni's
      equation and thermal activation of carriers out of constituent quantum dots.

PMID- 22480324
TI  - Abdominal venous thrombosis presenting in myeloproliferative neoplasm with JAK2
      V617F mutation: a case report.
AB  - INTRODUCTION: An unprovoked thombotic event in a patient is cause for further
      evaluation of an underlying hypercoaguable state. The investigation should
      include a thorough search, including checking for a variety of known inherited
      and acquired hypercoaguble states (protein C or S deficiency, anti-phospholipid
      antibodies, and anti-thrombin III deficiency) and gene mutations that predispose
      patients to an increased risk of clotting (for example, prothrombin gene 20210
      mutation, factor V Leiden, and the JAK2 V617F mutation). CASE PRESENTATION: We
      report the case of a 38-year-old Caucasian woman with spontaneous, unprovoked
      abdominal venous thrombosis and demonstrate how testing for the JAK2 V617F
      mutation was useful in unmasking an underlying hypercoaguable state. CONCLUSIONS:
      JAK2 V617F-positive myeloproliferative neoplasm was diagnosed. This case
      illustrates the importance of testing for JAK2 V617F in patients presenting with
      Budd-Chiari syndrome, even in the absence of overt hematologic abnormalities, in
      order to establish a diagnosis of underlying myeloproliferative neoplasm.

PMID- 22480325
TI  - Vibrational spectroscopic investigation of polymorphs and cocrystals of
      indomethacin.
AB  - CONTEXT: Identification of optimal solid form of an active pharmaceutical
      ingredient and form control are very important in drug development. Thus, the
      structural information of these forms and in-depth insight on the modes of
      molecular interactions are necessary, and vibrational spectroscopic methods are
      well suited for this purpose. OBJECTIVE: In-depth structural analysis of
      different solid forms of indomethacin (IND) using Raman and infrared (IR)
      spectroscopy is the objective. We have investigated the modes of molecular
      interactions in polymorphs (alpha and gamma), amorphous and discovered cocrystals
      of IND with nicotinamide (NIC) and trans-cinnamic acid (CIN) coformers. MATERIALS
      AND METHODS: The solid forms of IND have been prepared; their purity has been
      verified by differential scanning calorimetry and powder X-ray diffractometry and
      then studied in the solid-state by Raman and IR spectroscopy. The modes of the
      interactions were closely investigated from the vibrational data. RESULTS: The
      key vibrational features of IND solid forms have been specified. The IR (C=O)
      band at 1713 cm(-1) attributed to cyclic acid dimer of gamma IND has disappeared
      in IND-NIC/CIN whilst retained in IND-SAC cocrystal. DISCUSSION: IND
      cocrystallizes in different conformations and crystal lattices with different
      coformers. The cyclic acid dimer of IND has been kept on its cocrystallization
      with saccharin and it could have been broken with NIC and CIN. CONCLUSIONS: The
      complementary nature of Raman and IR spectroscopy allowed unambiguous
      investigation of the chemical composition of pharmaceutical materials which is of
      particular importance in the absence of detailed structural information, as in
      the case of IND-NIC and IND-CIN.

PMID- 22480326
TI  - Embryo and fetal toxicity of Mentha x villosa essential oil in Wistar rats.
AB  - CONTEXT: Mentha x villosa Hudson (Lamiaceae) is an aromatic herb employed as a
      food spice. In folk medicine, it leaves are used as a tranquilizer and anti
      hypertensive, even by pregnant women. OBJECTIVE: There are no reports about its
      effects in gestation and exposed fetuses, the aim of this study. MATERIALS AND
      METHODS: At gestation day (GD) 01, 24 rats were divided in four groups: one
      control and three experimental groups (n = 6/group). The experimental groups
      received, by gavage, from GD06 to GD16, 10, 25 or 50 ug/kg/day of Mentha x
      villosa essential oil. The control group received the vehicle (Tween 80 and
      distilled water--2%). The parameters of body weight gain, water and food intake
      were recorded. At GD20 the females were euthanized. Half of the fetuses from each
      litter were directed for the study of visceral malformations and the remaining
      fetuses for the study of skeletal malformations. RESULTS: The statistical
      analyses revealed absence of alterations in body weight gain, water and food
      intake, litter weight, fetuses number and weight, reabsorptions and
      implantations. The treatment revealed absence of visceral and skeletal
      malformations. The visceral analysis revealed mild hemorrhagic points at brain,
      but more numerous at kidney, liver and blood vessels near heart, in some fetuses
      from some experimental litters. CONCLUSION: The essential oil was not able to
      promote impairment to the pregnant rats and to gestation. Even occurring lack of
      malformations, fetotoxicity was revealed by mild hemorrhagic points at liver,
      kidney, brain and blood vessels of some exposed fetuses.

PMID- 22480327
TI  - CDAPubMed: a browser extension to retrieve EHR-based biomedical literature.
AB  - BACKGROUND: Over the last few decades, the ever-increasing output of scientific
      publications has led to new challenges to keep up to date with the literature. In
      the biomedical area, this growth has introduced new requirements for
      professionals, e.g., physicians, who have to locate the exact papers that they
      need for their clinical and research work amongst a huge number of publications.
      Against this backdrop, novel information retrieval methods are even more
      necessary. While web search engines are widespread in many areas, facilitating
      access to all kinds of information, additional tools are required to
      automatically link information retrieved from these engines to specific
      biomedical applications. In the case of clinical environments, this also means
      considering aspects such as patient data security and confidentiality or
      structured contents, e.g., electronic health records (EHRs). In this scenario, we
      have developed a new tool to facilitate query building to retrieve scientific
      literature related to EHRs. RESULTS: We have developed CDAPubMed, an open-source
      web browser extension to integrate EHR features in biomedical literature
      retrieval approaches. Clinical users can use CDAPubMed to: (i) load patient
      clinical documents, i.e., EHRs based on the Health Level 7-Clinical Document
      Architecture Standard (HL7-CDA), (ii) identify relevant terms for scientific
      literature search in these documents, i.e., Medical Subject Headings (MeSH),
      automatically driven by the CDAPubMed configuration, which advanced users can
      optimize to adapt to each specific situation, and (iii) generate and launch
      literature search queries to a major search engine, i.e., PubMed, to retrieve
      citations related to the EHR under examination. CONCLUSIONS: CDAPubMed is a
      platform-independent tool designed to facilitate literature searching using
      keywords contained in specific EHRs. CDAPubMed is visually integrated, as an
      extension of a widespread web browser, within the standard PubMed interface. It
      has been tested on a public dataset of HL7-CDA documents, returning significantly
      fewer citations since queries are focused on characteristics identified within
      the EHR. For instance, compared with more than 200,000 citations retrieved by
      breast neoplasm, fewer than ten citations were retrieved when ten patient
      features were added using CDAPubMed. This is an open source tool that can be
      freely used for non-profit purposes and integrated with other existing systems.

PMID- 22480328
TI  - Hydrolysis versus ion correlation models in electrokinetic charge inversion:
      establishing application ranges.
AB  - In this article, we investigate experimentally a wide range of situations where
      charge inversion (i.e., overcompensation of the surface charge of a colloidal
      particle by the countercharge) can occur. To that end, the electrophoretic
      mobility of sodium montmorillonite, silica, and polystyrene latex as functions of
      pH and concentration of different salts is presented, and conditions are
      established where charge inversion occurs. The reason for this study is to
      provide experimental evidence for distinguishing between two existing models for
      the explanation of charge inversion. One of these is the specific adsorption of
      ions located in the Stern layer in combination with a Gouy-Chapman diffuse part
      of the double layer. The other ion-correlation theories explain the phenomenon in
      terms of purely physical arguments based on Coulombic pair interactions between
      ions and surface charges and on excluded volume effects. In distinguishing
      between these two interpretations, the influence of the pH plays a central role
      because of its effect on the hydrolysis of multivalent cations. In our
      experiments, it is found that although 1-2 and 2-2 electrolytes provoke a
      decrease in the absolute values of the electrophoretic mobilities when their
      concentration in solution is increased, they never lead to charge inversion,
      whatever the surface charge or the pH. However, in the case of salts of trivalent
      cations, electrokinetic charge reversal is often observed above a certain
      critical electrolyte concentration. In addition, the extent of overcharging
      increases when the concentration is raised above the critical value. This trend
      occurs for any system in which the surface charge is pH-independent, as in
      polystyrene latex and montmorillonite. Most of the results presented here are
      compatible with the specific adsorption of hydrolyzed metal ions as the main
      driving force for charge inversion. At low pH, when the hydrolysis of trivalent
      cations is likely to be absent, overcharging can be attributed to ion correlation
      effects.

PMID- 22480330
TI  - Absorption, disposition, metabolism, and excretion of [3-(14)C]caffeic acid in
      rats.
AB  - Male Sprague-Dawley rats ingested 140 * 10(6) dpm of [3-(14)C]trans-caffeic acid,
      and over the ensuing 72 h period, body tissues, plasma, urine, and feces were
      collected and the overall levels of radioactivity determined. Where sufficient
      radioactivity had accumulated, samples were analyzed by HPLC with online
      radioactivity and tandem mass spectrometric detection. Nine labeled compounds
      were identified, the substrate and its cis isomer, 3'-O- and 4'-O-sulfates and
      glucuronides of caffeic acid, 4'-O-sulfates and glucuronides of ferulic acid, and
      isoferulic acid-4'-O-sulfate. Four unidentified metabolites were also detected.
      After passing down the gastrointestinal tract, the majority of the radiolabeled
      metabolites were excreted in urine with minimal accumulation in plasma. Only
      relatively small amounts of an unidentified (14)C-labeled metabolite were
      expelled in feces. There was little or no accumulation of radioactivity in body
      tissues, including the brain. The overall recovery of radioactivity 72 h after
      ingestion of [3-(14)C]caffeic acid was ~80% of intake.

PMID- 22480332
TI  - Phosphorylating reagent-free synthesis of 5'-phosphate oligonucleotides by
      controlled oxidative degradation of their 5'-end.
AB  - The 5'-phosphorylated oligonucleotides (5'-pONs) are currently synthesized using
      expensive and sensitive modified phosphoramidite reagents. In this work, a
      simple, cost-effective, efficient, and automatable method is presented, based on
      the controlled oxidation of the 5'-terminal alcohol followed by a beta
      elimination reaction. The latter reaction leads to the removal of the terminal 5'
      nucleoside and subsequent formation of the 5'-phosphate moiety. Thus, chemical
      phosphorylation of oligonucleotides (DNA or RNA) is achieved without using
      modified phosphoramidites.

PMID- 22480329
TI  - Function and biotechnology of extremophilic enzymes in low water activity.
AB  - Enzymes from extremophilic microorganisms usually catalyze chemical reactions in
      non-standard conditions. Such conditions promote aggregation, precipitation, and
      denaturation, reducing the activity of most non-extremophilic enzymes, frequently
      due to the absence of sufficient hydration. Some extremophilic enzymes maintain a
      tight hydration shell and remain active in solution even when liquid water is
      limiting, e.g. in the presence of high ionic concentrations, or at cold
      temperature when water is close to the freezing point. Extremophilic enzymes are
      able to compete for hydration via alterations especially to their surface through
      greater surface charges and increased molecular motion. These properties have
      enabled some extremophilic enzymes to function in the presence of non-aqueous
      organic solvents, with potential for design of useful catalysts. In this review,
      we summarize the current state of knowledge of extremophilic enzymes functioning
      in high salinity and cold temperatures, focusing on their strategy for function
      at low water activity. We discuss how the understanding of extremophilic enzyme
      function is leading to the design of a new generation of enzyme catalysts and
      their applications to biotechnology.

PMID- 22480333
TI  - Piceatannol suppresses breast cancer cell invasion through the inhibition of MMP
      9: involvement of PI3K/AKT and NF-kappaB pathways.
AB  - Cancer invasion and metastasis are the main causes of treatment failure and death
      in cancer patients. Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a
      natural analogue of resveratrol. This study investigated the anti-invasive
      mechanisms of piceatannol in MDA-MB-231 cells. Piceatannol significantly reduced
      serum-induced cell invasion and migration as well as adhesion without affecting
      the viability of cells. Furthermore, piceatannol markedly inhibited matrix
      metalloproteinase-9 (MMP-9) activity and expression at both protein and mRNA
      levels. Piceatannol attenuated phosphoinisitide-3-kinase (PI3K) and
      phosphorylation of AKT and mammalian target of rapamycin (mTOR), whereas
      phosphatase and tensin homologue (PTEN) was increased. Moreover, piceatannol
      inhibited nuclear factor kappa B (NF-kappaB) transcriptional activity and DNA
      binding of NF-kappaB on MMP-9 promoter. In addition, piceatannol diminished NF
      kappaB nuclear translocation through blocking the inhibitor of NF-kappaB alpha
      (IkappaBalpha) phosphorylation in the cytoplasm. These results proposed
      piceatannol as a potential anti-invasive agent by inhibiting MMP-9 involved in
      PI3K/AKT and NF-kappaB pathways.

PMID- 22480334
TI  - Reduction of nitrous acid with a macrocyclic rhodium complex that acts as a
      functional model of nitrite reductase.
AB  - Nitrous acid reacts with L(2)(H(2)O)Rh(2+) (L(2) = meso-hexamethylcyclam) in
      acidic aqueous solutions to generate a strongly absorbing intermediate Int-1
      (lambda(max) 400 nm, epsilon = 1200 M(-1) cm(-1)). The reaction follows a mixed
      second order rate law with k = (6.9 +/- 0.3) * 10(4) M(-1) s(-1), independent of
      [H(+)]. The lack of acid dependence shows that Int-1 is a rhodium(II) complex of
      HNO(2), most reasonably assigned as L(2)(H(2)O)Rh(HNO(2))(2+). This species is
      analogous to the early iron and copper intermediates in the reduction of nitrite
      by nitrite reductases and by deoxyhemoglobin. In the presence of excess
      L(2)(H(2)O)Rh(2+), the lifetime of Int-1 is about 1 min. It decays to a 1:1
      mixture of L(2)(H(2)O)RhNO(2+) and L(2)Rh(H(2)O)(2)(3+) with kinetics that are
      largely independent of the concentration of excess L(2)(H(2)O)Rh(2+) and of
      [H(+)] at [H(+)] < 0.03 M. At [H(+)] > 0.03 M, an acid-catalyzed pathway becomes
      effective, suggesting protonation and dehydration of Int-1 to generate
      L(2)(H(2)O)RhNO(3+) (Int-2) followed by rapid reduction of Int-2 by excess
      L(2)(H(2)O)Rh(2+). Int-2, which was generated and characterized independently, is
      an analog of the electrophilic intermediates in the mechanism of biological
      reduction of nitrite to (*)NO. Excess nitrite greatly reduces the lifetime of Int
      1, which under such conditions decomposes on a millisecond time scale by nitrite
      catalyzed disproportionation to yield L(2)(H(2)O)RhNO(2+) and L(2)Rh(III). This
      reaction provides additional support for the designation of Int-1 as a Rh(II)
      species. The complex reaction mechanism and the detection of Int-1 demonstrate
      the ability of inorganic complexes to perform the fundamental chemistry believed
      to take place in the biological reduction of HNO(2) to NO catalyzed by nitrite
      reductases or deoxyhemoglobin.

PMID- 22480335
TI  - Thermodynamic and kinetic stabilities of active site protonation states of class
      C beta-lactamase.
AB  - By employing computationally intensive molecular dynamics simulations using
      hybrid quantum-mechanical/molecular-mechanical approach, we analyze here the
      kinetic and thermodynamic stabilities of various active site protonation states
      of a fully solvated class C beta-lactamase. We report the detailed mechanism of
      proton transfer between catalytically important active site residues and the
      associated free energy barriers. In the apoenzyme, significant structural changes
      are associated with the proton transfer, and the orientations of active site
      residues are distinctly different for various protonation states. Among several
      propositions on the protonation state of the apoprotein, we find that the one
      with Tyr150 deprotonated and both Lys67 and Lys315 residues being protonated is
      the most stable one, both thermodynamically and kinetically. However, the
      equilibrium structure at room temperature is a dynamic one, with Lys315Hzeta
      delocalized between Tyr150Oeta and Lys315Nzeta. Of great importance, the kinetic
      and thermodynamic stability of protonation states are significantly affected on
      noncovalently complexing with cephalothin, an antibiotic molecule. The
      equilibrium structure of the enzyme-substrate (precovalent) complex has a dynamic
      protonation state where a proton shuttles frequently between the Tyr150Oeta and
      Lys67Nzeta. We examine here the genesis of the manifold change in stability at
      the molecular level. The importance of our observations toward understanding the
      reactivity of the enzyme is discussed and experimental observations are
      rationalized. 

PMID- 22480336
TI  - Comparative effectiveness of antihypertensive medication for primary prevention
      of cardiovascular disease: systematic review and multiple treatments meta
      analysis.
AB  - BACKGROUND: We conducted a systematic review of evidence from randomized
      controlled trials to answer the following research question: What are the
      relative effects of different classes of antihypertensive drugs in reducing the
      incidence of cardiovascular disease outcomes for healthy people at risk of
      cardiovascular disease? METHODS: We searched MEDLINE, EMBASE, AMED (up to
      February 2011) and CENTRAL (up to May 2009), and reference lists in recent
      systematic reviews. Titles and abstracts were assessed for relevance and those
      potentially fulfilling our inclusion criteria were then assessed in full text.
      Two reviewers made independent assessments at each step. We selected the
      following main outcomes: total mortality, myocardial infarction and stroke. We
      also report on angina, heart failure and incidence of diabetes. We conducted a
      multiple treatments meta-analysis using random-effects models. We assessed the
      quality of the evidence using the GRADE-instrument. RESULTS: We included 25
      trials. Overall, the results were mixed, with few significant differences, and
      with no drug-class standing out as superior across multiple outcomes. The only
      significant finding for total mortality based on moderate to high quality
      evidence was that beta-blockers (atenolol) were inferior to angiotensin receptor
      blockers (ARB) (relative risk (RR) 1.14; 95% credibility interval (CrI) 1.02 to
      1.28). Angiotensin converting enzyme (ACE)-inhibitors came out inferior to
      calcium-channel blockers (CCB) regarding stroke-risk (RR 1.19; 1.03 to 1.38), but
      superior regarding risk of heart failure (RR 0.82; 0.69 to 0.94), both based on
      moderate quality evidence. Diuretics reduced the risk of myocardial infarction
      compared to beta-blockers (RR 0.82; 0.68 to 0.98), and lowered the risk of heart
      failure compared to CCB (RR 0.73; 0.62 to 0.84), beta-blockers (RR 0.73; 0.54 to
      0.96), and alpha-blockers (RR 0.51; 0.40 to 0.64). The risk of diabetes increased
      with diuretics compared to ACE-inhibitors (RR 1.43; 1.12 to 1.83) and CCB (RR
      1.27; 1.05 to 1.57). CONCLUSION: Based on the available evidence, there seems to
      be little or no difference between commonly used blood pressure lowering
      medications for primary prevention of cardiovascular disease. Beta-blockers
      (atenolol) and alpha-blockers may not be first-choice drugs as they were the only
      drug-classes that were not significantly superior to any other, for any outcomes.
      Review registration: CRD database ("PROSPERO") CRD42011001066.

PMID- 22480337
TI  - Predicting the coordination number within copper chaperones: Atox1 as case study.
AB  - The concentration of copper ions in biological systems is tightly regulated by
      metallochaperone proteins which are responsible for Cu(I) delivery to designated
      locations in the cell. These proteins contain a unique motif (MXCXXC) that binds
      Cu(I) very tightly and specifically but at the same time allows efficient metal
      transfer to target proteins that often contain a similar copper binding motif. It
      was found that binding to Cu(I) is achieved through the two cysteine residues in
      a low coordination number of 2-3 due to possible binding of a third external
      ligand. Understanding copper transport requires better understanding of copper
      coordination. Here we therefore focused on establishing a computational method
      that can predict the coordination number of copper in copper chaperones. The
      method is shown to be successful in predicting the coordination of Cu(I) within
      the human copper chaperone (Atox1). Based on the results, a possible rationale
      for this unique Cu(I) dicoordination in Atox1 is suggested.

PMID- 22480338
TI  - Essentials for selecting antimicrobial therapy for intra-abdominal infections.
AB  - Intra-abdominal infection (IAI) is a complex disease entity in which different
      aspects must be balanced in order to select the proper antimicrobial regimen and
      determine duration of therapy. A current classification indicates different faces
      of peritonitis. Primary peritonitis implies an intact gastrointestinal tract
      without overt barrier disruption. Secondary peritonitis refers to localized or
      diffuse peritoneal inflammation and abscess formation due to disruption of the
      anatomical barrier. Tertiary peritonitis includes cases that cannot be solved by
      a single or even sequential surgical intervention, often in combination with
      sequential courses of antimicrobial therapy. The most frequently used
      classification distinguishes 'uncomplicated' and 'complicated' IAI. In
      uncomplicated IAI, the infectious process is contained within a single organ,
      without anatomical disruption. In complicated IAI, disease is extended, with
      either localized or generalized peritonitis. However, there exists more than a
      single dimension of complexity in IAI, including severity of disease expression
      through systemic inflammation. As the currently used classifications of IAI often
      incite confusion by mixing elements of anatomical barrier disruption, severity of
      disease expression and (the likelihood of) resistance involvement, we propose an
      alternative for the current widely accepted classification. We suggest abandoning
      the terms 'uncomplicated' and 'complicated' IAI, as they merely confuse the
      issue. Furthermore, the term 'tertiary peritonitis' should likewise be discarded,
      as this simply refers to treatment failure of secondary peritonitis resulting in
      a state of persistent infection and/or inflammation. Hence, anatomical disruption
      and disease severity should be separated into different phenotypes for the same
      disease in combination with either presence or absence of risk factors for
      involvement of pathogens that are not routinely covered in first-line
      antimicrobial regimens (Pseudomonas aeruginosa, enterococci, Candida species and
      resistant pathogens). Generally, these risk factors can be brought back to recent
      exposure to antimicrobial agents and substantial length of stay in healthcare
      settings (5-7 days). As such, we developed a grid based on the different
      components of the classification: (i) anatomical disruption; (ii) severity of
      disease expression; and (iii) either community-acquired/early-onset healthcare
      associated origin or healthcare-associated origin and/or recent antimicrobial
      exposure. The grid allows physicians to define the index case of IAI in a more
      unequivocal way and to select the most convenient empirical antimicrobial
      regimens. The grid advises on the necessity of covering nosocomial Gram-negative
      bacteria (including P. aeruginosa), enterococci and yeasts. The basis of
      antimicrobial therapy for IAI is that both Gram-negative and anaerobic bacteria
      should always be covered. In recent years, some newer agents such as doripenem,
      moxifloxacin and tigecycline have been added to the antimicrobial armamentarium
      for IAI. For patients in whom the source can be adequately controlled,
      antimicrobial therapy should be restricted to a short course (e.g. 3-7 days in
      peritonitis).

PMID- 22480339
TI  - Economic evaluation of treatment options in patients with Alzheimer's disease: a
      systematic review of cost-effectiveness analyses.
AB  - INTRODUCTION: Alzheimer's disease (AD) is common among the elderly; it is
      responsible for 60-80% of all dementia cases. AD is characterized by cognitive
      decline, behavioural and psychological symptoms, and reductions in functioning
      and independence. Because of its progressive neurodegenerative nature and unknown
      aetiology, the burden of AD becomes increasingly significant in an aging
      population. Estimates indicate that 35.6 million people worldwide suffered from
      AD in 2010. By 2030 and 2050, this figure is predicted to increase to 65.7
      million and 115.4 million, respectively. Costs will also rise along with the
      increase in the number of people diagnosed with AD. In 2010, the worldwide costs
      associated with dementia were estimated to be $US604 billion. OBJECTIVE: The
      objective of this study was to conduct a systematic review of current
      publications dealing with the pharmacoeconomic factors associated with AD
      medications and to describe the decision-analytic models used to evaluate long
      term outcomes. METHODS: A systematic literature search was performed to identify
      articles published between 1 January 2007 and 15 July 2010. The search was also
      based on a previous systematic review, which included literature up to 2007.
      Articles were included if they were complete and original economic evaluations of
      AD and if they were comparative in nature. A quality assessment of the included
      publications was conducted and relevant information was extracted into tables.
      RESULTS: Seven out of 2067 identified articles were included in this systematic
      review. Four articles evaluated treatment with donepezil, one with galantamine
      and two with memantine. The studies were conducted in America, Europe and Asia.
      Five different groups of medications were compared. The incremental cost
      effectiveness ratios (ICERs) for the group of patients treated with donepezil
      versus no drug treatment ranged from a dominant value to 281, 416.13 euros per
      quality-adjusted life-year (QALY). Patients treated with donepezil versus placebo
      showed ICERs with a range from a dominant value (not specified) up to 20, 866.77
      euros per QALY. Treatment with memantine in addition to donepezil versus
      treatment with donepezil alone showed an ICER range from a dominant value to
      6818.33 euros per QALY. In comparison with the memantine treatment as an add-on
      therapy, the ICER of memantine monotherapy versus standard care (without
      cholinesterase inhibitors [CEIs]) ranged from a dominant value to 63, 087.20
      euros per QALY. Finally, the economic evaluation of galantamine in comparison
      with usual care without any AD drugs showed ICERs ranging from 1894.70 euros to
      6953 euros per QALY. CONCLUSION: The seven identified publications included in
      this review indicate that treatment with CEIs or memantine seems to be reasonable
      in terms of clinical effects and costs for patients with AD. Depending on
      different hypotheses, assumptions and variables (e.g. time horizon, discount
      rates, initial number of patients in different states, etc.) in the sensitivity
      analyses, treatment with these drugs seems to be primarily a cost-effective
      strategy or even a cost-saving strategy. Nevertheless, the results generally are
      associated with a degree of uncertainty. The comparability of the results from
      the different economic evaluations is limited because of the different
      assumptions made.

PMID- 22480341
TI  - An explanatory randomised controlled trial of a nurse-led, consultation-based
      intervention to support patients with adherence to taking glucose lowering
      medication for type 2 diabetes.
AB  - BACKGROUND: Failure to take medication reduces the effectiveness of treatment
      leading to increased morbidity and mortality. We evaluated the efficacy of a
      consultation-based intervention to support objectively-assessed adherence to oral
      glucose lowering medication (OGLM) compared to usual care among people with type
      2 diabetes. METHODS: This was a parallel group randomised trial in adult patients
      with type 2 diabetes and HbA1c >= 7.5% (58 mmol/mol), prescribed at least one
      OGLM. Participants were allocated to a clinic nurse delivered, innovative
      consultation-based intervention to strengthen patient motivation to take OGLM
      regularly and support medicine taking through action-plans, or to usual care. The
      primary outcome was the percentage of days on which the prescribed dose of
      medication was taken, measured objectively over 12 weeks with an electronic
      medication-monitoring device (TrackCap, Aardex, Switzerland). The primary
      analysis was intention-to-treat. RESULTS: 211 patients were randomised between
      July 1, 2006 and November 30, 2008 in 13 British general practices (primary care
      clinics). Primary outcome data were available for 194 participants (91.9%). Mean
      (sd) percentage of adherent days was 77.4% (26.3) in the intervention group and
      69.0% (30.8) in standard care (mean difference between groups 8.4%, 95%
      confidence interval 0.2% to 16.7%, p = 0.044). There was no significant adverse
      impact on functional status or treatment satisfaction. CONCLUSIONS: This well
      specified, theory based intervention delivered in a single session of 30 min in
      primary care increased objectively measured medication adherence, with no adverse
      effect on treatment satisfaction. These findings justify a definitive trial of
      this approach to improving medication adherence over a longer period of time,
      with clinical and cost-effectiveness outcomes to inform clinical practice.

PMID- 22480342
TI  - Proteomic approach used in the diagnosis of Riedel's thyroiditis: a case report.
AB  - INTRODUCTION: Riedel's thyroiditis, a rare thyroid disease, can be difficult to
      diagnose prior to surgical removal and can be confused with malignancy both
      clinically and cytologically. CASE PRESENTATION: We report the case of a 72-year
      old Caucasian woman who presented with a goiter, which showed a rapid increase in
      size at ultrasound check, suggesting malignancy. Because of inconclusive
      cytology, a total thyroidectomy was performed. Fine-needle aspiration of the
      removed thyroid was processed by two-dimensional electrophoresis, and the
      proteome was compared with both anaplastic cancer and control samples.
      Significant differentially expressed protein spots were identified by Western
      blot analysis by using specific antibodies. CONCLUSIONS: The protein pattern of
      Riedel's fine-needle aspiration revealed a superimposition with that of the
      control samples. The comparison of the protein pattern of Riedel's thyroiditis
      fine-needle aspiration with that of anaplastic cancer showed evidence of a
      different expression of ferritin heavy chains, ferritin light chains, and
      haptoglobins, as previously reported in thyroid cancers. Therefore, we performed
      Western blot analysis of these proteins and validated that their expression
      levels were low or absent in Riedel's thyroiditis and control samples despite the
      high concentrations present in fine-needle aspiration anaplastic samples. The
      concurrent absent or low expression levels of haptoglobin, ferritin light chain,
      and ferritin heavy chain in Riedel's thyroiditis fine-needle aspiration samples
      strongly indicate the benign nature of the thyroid lesion. These results suggest
      the potential applicability of fine-needle aspiration proteome analysis for
      Riedel's thyroiditis diagnosis.

PMID- 22480343
TI  - On the use of the dual process Langmuir model for predicting unary and binary
      isosteric heats of adsorption.
AB  - Analytic expressions for unary and binary isosteric heats of adsorption as a
      function of the adsorbed phase loading were derived from the dual process
      Langmuir (DPL) model using the Clausius-Clapeyron equation. Unary isosteric heats
      of adsorption predicted from these expressions for several adsorbate-adsorbent
      systems were compared to values in the literature predicted from the well
      accepted graphical approach using Toth and unilan models (Adsorption Equilibrium
      Data Handbook; Prentice Hall: NJ, 1989). Predictions from the DPL model were also
      compared to rare experimental unary and binary isosteric heats of adsorption in
      the literature for another adsorbate-adsorbent system. In all cases, very good
      agreement was obtained, showing that the DPL model can be used in adsorption
      process modeling for accurately predicting not only ideal and nonideal mixed-gas
      adsorption equilibria (Langmuir 2011, 27, 4700), but also unary and even binary
      isosteric heats of adsorption.

PMID- 22480340
TI  - Statins and pregnancy: between supposed risks and theoretical benefits.
AB  - Cardiovascular diseases are the leading cause of mortality in industrialized
      countries. Treatment with statins is effective in primary prevention in patients
      at high cardiovascular risk. Statins are inhibitors of hydroxymethylglutaryl
      coenzyme A (HMG-CoA) reductase and are classed as lipid-lowering drugs. In 2010,
      atorvastatin was the biggest-selling drug in the world ($US10.73 billion).
      Increases in the average age of pregnant women and in the prevalence of morbid
      obesity have inevitably led to exposure to statins in certain women during the
      first trimester of pregnancy. The teratogenic risk attendant upon use of statins
      is unclear because the available data are contradictory, but statins remain
      contraindicated in pregnant women. The benefits of statins in prevention of
      cardiovascular risk may not be solely due to their cholesterol-lowering effects:
      the so-called pleiotropic effects of vascular protection lead some experts to
      posit a potential benefit in the management of preeclampsia. In this review we
      evaluate the theoretical benefits and supposed risks of statins in pregnant
      women. After a brief overview of the pharmacodynamic properties of statins, we
      address the question of the teratogenic risk of statins, and then detail the
      rationale for the therapeutic potential of statins in preeclampsia.

PMID- 22480344
TI  - Structure-based and multiple potential three-dimensional quantitative structure
      activity relationship (SB-MP-3D-QSAR) for inhibitor design.
AB  - The inhibitions of enzymes (proteins) are determined by the binding interactions
      between ligands and targeting proteins. However, traditional QSAR (quantitative
      structure-activity relationship) is a one-side technique, only considering the
      structures and physicochemical properties of inhibitors. In this study, the
      structure-based and multiple potential three-dimensional quantitative structure
      activity relationship (SB-MP-3D-QSAR) is presented, in which the structural
      information of host protein is involved in the QSAR calculations. The SB-MP-3D
      QSAR actually is a combinational method of docking approach and QSAR technique.
      Multiple docking calculations are performed first between the host protein and
      ligand molecules in a training set. In the targeting protein, the functional
      residues are selected, which make the major contribution to the binding free
      energy. The binding free energy between ligand and targeting protein is the
      summation of multiple potential energies, including van der Waals energy,
      electrostatic energy, hydrophobic energy, and hydrogen-bond energy, and may
      include nonthermodynamic factors. In the foundational QSAR equation, two sets of
      weighting coefficients {aj} and {bp} are assigned to the potential energy terms
      and to the functional residues, respectively. The two coefficient sets are solved
      by using iterative double least-squares (IDLS) technique in the training set.
      Then, the two sets of weighting coefficients are used to predict the
      bioactivities of inquired ligands. In an application example, the new developed
      method obtained much better results than that of docking calculations.

PMID- 22480345
TI  - Quantification of sleepiness through principal component analysis of the
      electroencephalographic spectrum.
AB  - Although circadian and sleep research has made extraordinary progress in the
      recent years, one remaining challenge is the objective quantification of
      sleepiness in individuals suffering from sleep deprivation, sleep restriction,
      and excessive somnolence. The major goal of the present study was to apply
      principal component analysis to the wake electroencephalographic (EEG) spectrum
      in order to establish an objective measure of sleepiness. The present analysis
      was led by the hypothesis that in sleep-deprived individuals, the time course of
      self-rated sleepiness correlates with the time course score on the 2nd principal
      component of the EEG spectrum. The resting EEG of 15 young subjects was recorded
      at 2-h intervals for 32-50 h. Principal component analysis was performed on the
      sets of 16 single-Hz log-transformed EEG powers (1-16 Hz frequency range). The
      time course of self-perceived sleepiness correlated strongly with the time course
      of the 2nd principal component score, irrespective of derivation (frontal or
      occipital) and of analyzed section of the 7-min EEG record (2-min section with
      eyes open or any of the five 1-min sections with eyes closed). This result
      indicates the possibility of deriving an objective index of physiological
      sleepiness by applying principal component analysis to the wake EEG spectrum.

PMID- 22480346
TI  - Influence of a nano phase segregation on the thermoelectric properties of the p
      type doped stannite compound Cu(2+x)Zn(1-x)GeSe4.
AB  - Engineering nanostructure in bulk thermoelectric materials has recently been
      established as an effective approach to scatter phonons, reducing the phonon mean
      free path, without simultaneously decreasing the electron mean free path for an
      improvement of the performance of thermoelectric materials. Herein the synthesis,
      phase stability, and thermoelectric properties of the solid solutions Cu(2+x)Zn(1
      x)GeSe(4) (x = 0-0.1) are reported. The substitution of Zn(2+) with Cu(+)
      introduces holes as charge carriers in the system and results in an enhancement
      of the thermoelectric efficiency. Nano-sized impurities formed via phase
      segregation at higher dopant contents have been identified and are located at the
      grain boundaries of the material. The impurities lead to enhanced phonon
      scattering, a significant reduction in lattice thermal conductivity, and
      therefore an increase in the thermoelectric figure of merit in these materials.
      This study also reveals the existence of an insulator-to-metal transition at 450
      K.

PMID- 22480347
TI  - Why do health workers in rural Tanzania prefer public sector employment?
AB  - BACKGROUND: Severe shortages of qualified health workers and geographical
      imbalances in the workforce in many low-income countries require the national
      health sector management to closely monitor and address issues related to the
      distribution of health workers across various types of health facilities. This
      article discusses health workers' preferences for workplace and their perceptions
      and experiences of the differences in working conditions in the public health
      sector versus the church-run health facilities in Tanzania. The broader aim is to
      generate knowledge that can add to debates on health sector management in low
      income contexts. METHODS: The study has a qualitative study design to elicit in
      depth information on health workers' preferences for workplace. The data comprise
      ten focus group discussions (FGDs) and 29 in-depth interviews (IDIs) with
      auxiliary staff, nursing staff, clinicians and administrators in the public
      health sector and in a large church-run hospital in a rural district in Tanzania.
      The study has an ethnographic backdrop based on earlier long-term fieldwork in
      Tanzania. RESULTS: The study found a clear preference for public sector
      employment. This was associated with health worker rights and access to various
      benefits offered to health workers in government service, particularly the
      favourable pension schemes providing economic security in old age. Health workers
      acknowledged that church-run hospitals generally were better equipped and
      provided better quality patient care, but these concerns tended to be outweighed
      by the financial assets of public sector employment. In addition to the sector
      specific differences, family concerns emerged as important in decisions on
      workplace. CONCLUSIONS: The preference for public sector employment among health
      workers shown in this study seems to be associated primarily with the favourable
      pension scheme. The overall shortage of health workers and the distribution
      between health facilities is a challenge in a resource constrained health system
      where church-run health facilities are vital in the provision of health care in
      rural areas and where patients tend to prefer these services. In order to ensure
      equity in distribution of qualified health workers in Tanzania, a national
      regulation and legislation of the pension schemes is required.

PMID- 22480348
TI  - Total synthesis of nominal (11S)- and (11R)-cyclocinamide A.
AB  - The cyclocinamides possess a unique beta(2)alphabeta(2)alpha 14-membered
      tetrapeptide core. The initially reported biological data and intriguing
      structure, which was without full stereochemical identification, necessitated
      synthesis of both nominal (all-S) cyclocinamide A and the 11R isomer. The
      completed synthesis is highlighted by the use of a (cyclo)asparagine-containing
      dipeptide as a turn inducing fragment. Due to inconsistencies in analytical data
      between natural and synthetic samples, a re-evaluation of the natural product
      stereochemistry appears necessary.

PMID- 22480349
TI  - New triterpenoids from Morus alba L. stem bark.
AB  - Two lupeol-type pentacyclic triterpenoids characterised as lup-20(29)-en-3beta-ol
      27-oic acid (moruslupenoic acid A) and lup-12, 20(29)-dien-3beta-ol-26-oic acid
      (moruslupenoic acid B) and lanst-5, 24-dien-3beta-yl acetate (moruslanosteryl
      acetate) along with the known triterpenoidal phytoconstituents alpha-amyrin
      acetate, beta-amyrin-beta-D-glucopyranoside and betulinic acid have been isolated
      from the stem bark of Morus alba L. (Moraceae). The structures of the isolated
      phytoconstituents were established on the basis of spectral data analysis and
      chemical means.

PMID- 22480350
TI  - Antithrombotic effect of a novel protein from Fusarium sp. CPCC 480097 in a rat
      model of artery-vein bypass thrombosis.
AB  - CONTEXT: The incidence and mortality of thrombotic disorders are rapidly
      increasing throughout the world. Therefore, attempts have been made to develop
      new anticoagulant and antithrombotic drugs. Our previous studies showed that a
      novel protein, named Fu-P, had fibrinogenolytic activity and much higher
      fibrinolytic activity on the fibrin plate than urokinase in vitro. OBJECTIVE: The
      antithrombotic activities of Fu-P in vivo are investigated here for the first
      time. MATERIALS AND METHODS: Antithrombotic activity of Fu-P was studied in a rat
      model of artery-vein bypass thrombosis. The anticoagulant activity of Fu-P was
      measured by clotting assay of activated partial thrombinplastin time and
      prothrombin time (PT). The effects of Fu-P on the factor Xa and thrombin were
      assayed using the chromogenic substrate S-2765 and S-2238. RESULTS: Intravenous
      injection of Fu-P produced a 58.4% inhibition ratio of thrombus formation at 0.1
      mg/kg body weight, while heparin produced 42.5% inhibition ratio of thrombus
      formation at 0.6 mg/kg body weight. Fu-P significantly prolonged fibrinogen
      clotting time, activated partial thrombinplastin time and thrombin time, which
      also prolonged PT. The inhibition assay of the coagulant factors using
      chromogenic substrates S-2238 and S-2765 showed that Fu-P was not the inhibitor
      of the thrombin and Xa. DISCUSSION AND CONCLUSION: These findings demonstrated
      that the novel fibrinolytic enzyme (Fu-P) might also be used as a natural agent
      for thrombolytic therapy or thrombosis prevention.

PMID- 22480352
TI  - Dispersive cleanup of acetonitrile extracts of tea samples by mixed multiwalled
      carbon nanotubes, primary secondary amine, and graphitized carbon black sorbents.
AB  - A method for analysis of 37 pesticide residues in tea samples was developed and
      validated and was based on reversed-dispersive solid-phase extraction (r-DSPE)
      cleanup in acetonitrile solution, followed by liquid chromatography-electrospray
      tandem mass spectrometry determination. Green tea, oolong tea, and puer tea were
      selected as matrixes and represent the majority of tea types. Acetonitrile was
      used as the extraction solvent, with sodium chloride and magnesium sulfate
      enhancing partitioning of analytes into the organic phase. The extract was then
      cleaned up by r-DSPE using a mixture of multiwalled carbon nanotubes, primary
      secondary amine, and graphitized carbon black as sorbents to absorb
      interferences. Further optimization of sample preparation and determination
      allowed recoveries of between 70% and 111% for all 37 pesticides with relative
      standard deviations lower than 14% at two concentration levels of 10 and 100 MUg
      kg(-1). Limits of quantification ranged from 5 to 20 MUg kg(-1) for all
      pesticides. The developed method was successfully applied to the determination of
      pesticide residues in market tea samples.

PMID- 22480353
TI  - Virtual reality games for movement rehabilitation in neurological conditions: how
      do we meet the needs and expectations of the users?
AB  - PURPOSE: To review quantitative and qualitative studies that have examined the
      users' response to virtual reality game-based interventions in people with
      movement disorders associated with chronic neurological conditions. We aimed to
      determine key themes that influenced users' enjoyment and engagement in the games
      and develop suggestions as to how future systems could best address their needs
      and expectations. KEY MESSAGE AND IMPLICATIONS: There were a limited number of
      studies that evaluated user opinions. From those found, seven common themes
      emerged: technology limitations, user control and therapist assistance, the novel
      physical and cognitive challenge, feedback, social interaction, game purpose and
      expectations, and the virtual environments. Our key recommendations derived from
      the review were to avoid technology failure, maintain overt therapeutic
      principles within the games, encompass progression to promote continuing physical
      and cognitive challenge, and to provide feedback that is easily and readily
      associated with success. CONCLUSIONS: While there have been few studies that have
      evaluated the users' perspective of virtual rehabilitation games, our findings
      indicate that canvassing these experiences provides valuable information on the
      needs of the intended users. Incorporating our recommendations may enhance the
      efficacy of future systems to optimize the rehabilitation benefits of virtual
      reality games.

PMID- 22480351
TI  - Spectroscopic characterization of active-site variants of the PduO-type
      ATP:corrinoid adenosyltransferase from Lactobacillus reuteri: insights into the
      mechanism of four-coordinate Co(II)corrinoid formation.
AB  - The PduO-type adenosine 5'-triphosphate (ATP):corrinoid adenosyltransferase from
      Lactobacillus reuteri (LrPduO) catalyzes the transfer of the adenosyl-group of
      ATP to Co(1+)cobalamin (Cbl) and Co(1+)cobinamide (Cbi) substrates to synthesize
      adenosylcobalamin (AdoCbl) and adenosylcobinamide (AdoCbi(+)), respectively.
      Previous studies revealed that to overcome the thermodynamically challenging
      Co(2+) -> Co(1+) reduction, the enzyme drastically weakens the axial ligand
      Co(2+) bond so as to generate effectively four-coordinate (4c) Co(2+)corrinoid
      species. To explore how LrPduO generates these unusual 4c species, we have used
      magnetic circular dichroism (MCD) and electron paramagnetic resonance (EPR)
      spectroscopic techniques. The effects of active-site amino acid substitutions on
      the relative yield of formation of 4c Co(2+)corrinoid species were examined by
      performing eight single-amino acid substitutions at seven residues that are
      involved in ATP-binding, an intersubunit salt bridge, and the hydrophobic region
      surrounding the bound corrin ring. A quantitative analysis of our MCD and EPR
      spectra indicates that the entire hydrophobic pocket below the corrin ring, and
      not just residue F112, is critical for the removal of the axial ligand from the
      cobalt center of the Co(2+)corrinoids. Our data also show that a higher level of
      coordination among several LrPduO amino acid residues is required to exclude the
      dimethylbenzimidazole moiety of Co(II)Cbl from the active site than to remove the
      water molecule from Co(II)Cbi(+). Thus, the hydrophilic interactions around and
      above the corrin ring are more critical to form 4c Co(II)Cbl than 4c
      Co(II)Cbi(+). Finally, when ATP analogues were used as cosubstrate, only
      "unactivated" five-coordinate (5c) Co(II)Cbl was observed, disclosing an
      unexpectedly large role of the ATP-induced active-site conformational changes
      with respect to the formation of 4c Co(II)Cbl. Collectively, our results indicate
      that the level of control exerted by LrPduO over the timing for the formation of
      the 4c Co(2+)corrinoid intermediates is even more exquisite than previously
      anticipated.

PMID- 22480354
TI  - Surface nanopatterns of two types of banded spherulites in poly(nonamethylene
      terephthalate) thin films.
AB  - Surface nanopatterns of dual ring-banded spherulites in poly(nonamethylene
      terephthalate) (PNT) were investigated using polarized optical microscopy (POM)
      and atomic force microscopy (AFM). The surface morphology differs between narrow
      spaced single ring bands versus widely spaced double ring bands in spherulites,
      labeled Type-1 and Type-2, respectively. Ridge and valley consist of two discrete
      species ranging from nano- to micrometer-sized crystals shaped and oriented
      differently. Ridges of Type-1 and Type-2 spherulites apparently differ in shapes
      of the crystal plates. AFM height profile analysis reveals that the ridge of Type
      2 ring-banded spherulite is higher than that of Type-1 spherulites. The crystal
      packing on the ridges and valley of these two types of ring-banded was further
      compared using high-magnification AFM phase imaging. There exists a transition
      zone in going from the ridge and valley regions in the Type-2 ring-banded
      spherulites crystallized at Tc = 75-85  degrees C; the crystals on the transition
      zone change gradually in sizes and orientation from those in the ridge to valley.
      By contrast, Type-1 ring-banded spherulite does not have this kind of transition
      zone, meaning that crystals in the ridges abruptly submerge into valley in Type-1
      ring-banded spherulites. Details of packing of nanosize crystals in forming ridge
      and valleys of these two ring band types are discussed. 

PMID- 22480355
TI  - A retrospective study of gastric dilatation and gastric dilatation and volvulus
      in working farm dogs in New Zealand.
AB  - AIMS: To present findings from a case series of gastric dilatation (GD) or
      gastric dilatation and volvulus (GDV) in working farm dogs in New Zealand that
      were examined at veterinary clinics, and to identify possible risk factors for GD
      or GDV in working farm dogs in New Zealand using a case-control study. METHODS:
      This retrospective study included a case-series and a case-control study. The
      case series analysed information from 62 case records of GD or GDV in working
      farm dogs seen between August 2004 and September 2009 at 13 veterinary clinics
      throughout New Zealand. Cases were classified as GD or GDV if the diagnosis was
      confirmed by radiography, surgery or post-mortem examination. Details of history
      and treatment, as well as outcomes, were obtained for each case. For the case
      control study, records of 41 working farm dogs with GD or GDV (cases) seen
      between April 2008 and April 2009, and 82 working farm dogs examined because of
      trauma over the same period and in the same 13 clinics (controls), were used to
      model the risk factors for GD or GDV. RESULTS: From the case-series study, 40/62
      (65%) cases of GD or GDV that were examined and treated at the veterinary clinics
      returned to work. Of the 41 dogs where the gastric contents were recorded, 25
      (61%) had predominantly food or bones in the stomach, and 26/27 dogs had a
      history of having eaten meat, bones or scavenged a carcass. The case-control
      study showed that the significant risk factors for GD or GDV, compared with
      control dogs presenting with trauma, were breed, age and season. The odds that a
      case of GD or GDV was a Huntaway, after adjusting for age and season, was 19
      times higher than the odds a control was a Huntaway. Gender and bodyweight were
      not identified as risk factors. CONCLUSIONS AND CLINICAL RELEVANCE: A high
      proportion of farm working dogs with GD or GDV were successfully treated by
      veterinarians. The risk of a case of GD or GDV being a Huntaway was significantly
      higher than for a dog presenting as a trauma case. However the influences of the
      season of the year, climatic factors and nutritional factors on the pathogenesis
      need to be identified before adequate preventative measures can be recommended.

PMID- 22480356
TI  - Excretion of loline alkaloids in urine and faeces of sheep dosed with meadow
      fescue (Festuca pratensis) seed containing high concentrations of loline
      alkaloids.
AB  - AIM: To determine the effect of oral dosing of sheep with loline alkaloids on
      their excretion in urine and faeces, and to monitor for any toxic effects.
      METHODS: In Experiment 1, six 9-month-old ewe lambs were given a single oral dose
      of loline alkaloids (52 mg/kg bodyweight (BW); acute exposure) as a suspension of
      ground meadow fescue (Festuca pratensis) seed in water. In Experiment 2, on six
      consecutive days, six ewe lambs were given three doses of loline (68 mg/kg
      BW/day; chronic exposure). Blood was collected at variable intervals up to 72 h
      in Experiment 1, and up to 8 days in Experiment 2, for haematology and
      measurement of alkaline phosphatase, aspartate aminotransaminase, creatine kinase
      and gamma-glutamyl transferase in plasma. Urine and faecal samples were collected
      at similar times for measurement of creatinine in urine and loline alkaloid
      analysis. A post mortem with histopathology was carried out on two animals at the
      end of each experiment. RESULTS: The loline alkaloids, N-acetyl norloline, N
      formyl loline, N-acetyl loline, N-methyl loline and loline base were detected in
      urine within 15 minutes after the single dosing. N-formyl loline and loline base
      were the predominant metabolites in urine in both experiments. The total quantity
      of lolines excreted in both urine and faeces was 10% and 4% of the amount dosed
      in Experiments 1 and 2, respectively. In both experiments, the clinical chemistry
      parameters in blood and urine were within normal ranges. Post-mortem and
      histopathological examination did not show any abnormalities. CONCLUSIONS: This
      is the first report of loline alkaloid profiles in both urine and faeces of
      sheep. The appearance of loline alkaloids and the loline base in urine within 15
      minutes suggests rapid uptake, metabolism and excretion. Loline alkaloids were
      non-toxic to sheep at the concentrations they are exposed to under New Zealand
      grazing conditions. The low recovery of loline alkaloids in urine and faeces in
      the absence of toxicity signs suggests lolines are extensively metabolised;
      probably to forms other than N-formyl loline, N-methyl loline, N-acetyl loline, N
      acetyl norloline, and loline base in the digestive tract of sheep prior to
      absorption, and/or in the liver or other tissues following absorption.

PMID- 22480357
TI  - Effect of oxytocin on suppression of oestrus in mares exhibiting normal oestrous
      cycles.
AB  - AIM: To compare the efficacy of oxytocin given once daily, either I/V or I/M, on
      Days 7-14 post-ovulation, on the expression of oestrus in mares through to 65
      days post-ovulation. METHODS: Eighteen mares of various breeds that were
      displaying normal oestrous cycles were randomly assigned to one of three
      treatment groups on the day of ovulation (Day 0), detected using transrectal
      ultrasonography. Mares in the control group (n = 6) were given 1 mL saline I/V;
      mares in the I/V and I/M groups (n = 6 per group) were injected with 10 IU
      oxytocin I/V and I/M, respectively. All treatments were given once daily on Days
      7-14. Mares were teased by a stallion three times per week, up to 65 days post
      ovulation, to detect oestrous or dioestrous behaviour. Ovarian follicular and
      luteal activity were monitored using transrectal ultrasonography three times
      weekly, and daily when a follicle >30 mm diameter was present until ovulation.
      Blood samples were collected weekly for analysis of concentrations of
      progesterone in serum. Prolonged dioestrus was defined as a period of >30 days of
      dioestrous behaviour after Day 0, confirmed by detection of corpora lutea and
      concentrations of progesterone in serum >4 nmol/L. RESULTS: Overall, 8/18 (44%)
      mares showed prolonged dioestrus. These included 2/6 (33%) mares in the control
      group, compared with 5/6 (83%) and 1/6 (16%) mares in the I/V and I/M groups,
      respectively (p = 0.11). The median duration of the first dioestrus was longer
      for the I/V group (64 (min 16, max 66) days) compared with the control group (18
      (min 12, max 64) days) (p = 0.05), but was not different between the control
      group and the I/M group (16 (min 13, max 65) days) (p = 0.57). For all mares
      there was strong agreement between teasing behaviours, ultrasonographic
      assessment of ovarian activity, and concentration of progesterone in serum.
      CONCLUSIONS AND CLINICAL RELEVANCE: This study found that low doses of oxytocin
      did not increase the proportion of mares with prolonged dioestrus, compared with
      controls, although I/V oxytocin did increase the median duration of dioestrus.
      The results must be interpreted with some caution as group numbers were small,
      and a variety of breeds were used. Further investigation of oxytocin given I/V
      may be warranted as a potential method of oestrus suppression in mares exhibiting
      oestrous cycles that is low cost, safe and well-tolerated, and potentially
      reversible with prostaglandin.

PMID- 22480358
TI  - Bilateral ovarian adenocarcinoma in a mare causing haemoperitoneum and colic.
AB  - CASE HISTORY: A 13-year-old Thoroughbred mare was presented with a history of
      mild colic over 3 days. This colic had acutely exacerbated and was unresponsive
      to analgesic treatment, and was referred to Massey University Veterinary Teaching
      Hospital. CLINICAL FINDINGS: On examination the heart rate was 100 beats per
      minute, and mucous membranes were pale and tacky. A large mass was detected on
      transrectal palpation in the caudal abdomen to the left of midline. Explorative
      laparotomy revealed severe haemoperitoneum and several masses that were
      associated with the reproductive tract. The mare was then subject to euthanasia.
      On post-mortem examination, adjacent and attached to each ovary were soft,
      lobulated dark red masses up to 200 mm in diameter. Similar masses were present
      in the omentum and on the peritoneal surface of the diaphragm and the serosa of
      the spleen and liver. Histopathology revealed that the neoplastic component of
      the masses comprised proliferating cuboidal to columnar cells forming
      disorganised acini and cords separated by dense collagenous stroma.
      Immunohistochemistry showed the neoplastic cells were positive for cytokeratin
      AE1/AE3 and vimentin, but negative for cytokeratin 7 and inhibin alpha.
      DIAGNOSIS: Bilateral ovarian adenocarcinoma with transcoelomic metastasis and
      terminal decompensation due to rupture of a neoplastic mass and consequent
      haemoperitoneum. CLINICAL RELEVANCE: To the authors' knowledge, bilateral ovarian
      adenocarcinoma has not been previously reported in a horse. Ovarian
      adenocarcinoma should be considered when horses present with haemoperitoneum and
      colic. Further research is required on the immunohistochemical differentiation of
      adenocarcinoma of ovarian and intestinal origin in the horse.

PMID- 22480359
TI  - Guttural pouch mycosis in six horses in New Zealand.
AB  - CASE HISTORIES: Six horses from several geographical locations in New Zealand
      presented with signs of guttural pouch mycosis. All horses had experienced
      epistaxis within 14 days of presentation. CLINICAL FINDINGS AND TREATMENT: In
      five horses with epistaxis, a diagnosis of guttural pouch mycosis was made on
      endoscopic observation of fungal plaques in the affected guttural pouches. One of
      these cases died before surgery was attempted. The remaining four cases underwent
      ligation and balloon catheter occlusion of the internal carotid artery of the
      affected pouch. Three of these horses survived and were reported to be healthy 1
      year after surgery. One case died from haemorrhage 8 weeks after surgery. In a
      sixth horse, endoscopy was carried out but the affected guttural pouch which had
      recently haemorrhaged was not entered. This horse underwent ligation of the
      internal carotid and occipital arteries of the affected side but subsequently
      died. A diagnosis of guttural pouch mycosis of the maxillary artery was confirmed
      by post-mortem examination. Histology revealed fungal hyphae within thrombi in
      the lumen of the maxillary artery in the affected guttural pouch. Two horses
      displayed signs consistent with cranial nerve damage in the guttural pouch.
      DIAGNOSIS: Guttural pouch mycosis. CLINICAL RELEVANCE: This is the first report
      of which we are aware of the diagnosis and treatment of clinical cases of
      guttural pouch mycosis in horses in New Zealand. Practitioners in New Zealand
      should be aware of the presence and manifestations of this disease and be
      prepared to treat or refer horses for surgical treatment before fatal haemorrhage
      and/or profound neurologic signs occur.

PMID- 22480360
TI  - Use of parenteral long-acting and topical oxytetracycline, without hoof trimming,
      for treatment of footrot in goats.

PMID- 22480361
TI  - The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory
      mediators via improvement in peroxisomal function.
AB  - BACKGROUND: Inflammation is known to play a pivotal role in mediating neuronal
      damage and axonal injury in a variety of neurodegenerative disorders. Among the
      range of inflammatory mediators, nitric oxide and hydrogen peroxide are potent
      neurotoxic agents. Recent evidence has suggested that oligodendrocyte peroxisomes
      may play an important role in protecting neurons from inflammatory damage.
      METHODS: To assess the influence of peroxisomal activation on nitric oxide
      mediated neurotoxicity, we investigated the effects of the peroxisomal
      proliferator activated receptor (PPAR) gamma agonist, pioglitazone in primary
      cortical neurons that were either exposed to a nitric oxide donor or co-cultured
      with activated microglia. RESULTS: Pioglitazone protected neurons and axons
      against both nitric-oxide donor-induced and microglia-derived nitric oxide
      induced toxicity. Moreover, cortical neurons treated with this compound showed a
      significant increase in the protein and gene expression of PPAR-gamma, which was
      associated with a concomitant increase in the enzymatic activity of catalase. In
      addition, the protection of neurons and axons against hydrogen peroxide-induced
      toxicity afforded by pioglitazone appeared to be dependent on catalase.
      CONCLUSIONS: Collectively, these observations provide evidence that modulation of
      PPAR-gamma activity and peroxisomal function by pioglitazone attenuates both NO
      and hydrogen peroxide-mediated neuronal and axonal damage suggesting a new
      therapeutic approach to protect against neurodegenerative changes associated with
      neuroinflammation.

PMID- 22480362
TI  - Phenotypic characterization and 16S rDNA identification of culturable non
      obligate halophilic bacterial communities from a hypersaline lake, La Sal del
      Rey, in extreme South Texas (USA).
AB  - BACKGROUND: La Sal del Rey ("the King's Salt") is one of several naturally
      occurring salt lakes in Hidalgo County, Texas and is part of the Lower Rio Grande
      Valley National Wildlife Refuge. The research objective was to isolate and
      characterize halophilic microorganisms from La Sal del Rey. Water samples were
      collected from the lake and a small creek that feeds into the lake. Soil samples
      were collected from land adjacent to the water sample locations. Sample salinity
      was determined using a refractometer. Samples were diluted and cultured on a
      synthetic saline medium to grow halophilic bacteria. The density of halophiles
      was estimated by viable plate counts. A collection of isolates was selected, gram
      stained, tested for catalase, and characterized using API 20E(r) test strips.
      Isolates were putatively identified by sequencing the 16S rDNA. Carbon source
      utilization by the microbial community from each sample site was examined using
      EcoPlateTM assays and the carbon utilization total activity of the community was
      determined. RESULTS: Results showed that salinity ranged from 4 parts per
      thousand (ppt) at the lake water source to 420 ppt in water samples taken just
      along the lake shore. The density of halophilic bacteria in water samples ranged
      from 1.2 * 102 - 5.2 * 103 colony forming units per ml (cfu ml-1) whereas the
      density in soil samples ranged from 4.0 * 105 - 2.5 * 106 colony forming units
      per gram (cfu g-1). In general, as salinity increased the density of the
      bacterial community decreased. Microbial communities from water and soil samples
      were able to utilize 12 - 31 carbon substrates. The greatest number of substrates
      utilized was by water-borne communities compared to soil-based communities,
      especially at lower salinities. The majority of bacteria isolated were gram
      negative, catalase-positive, rods. Biochemical profiles constructed from API
      20E(r) test strips showed that bacterial isolates from low-salinity water samples
      (4 ppt) showed the greatest phenotypic diversity with regards to the types and
      number of positive tests from the strip. Isolates taken from water samples at the
      highest salinity (420 ppt) tended to be less diverse and have only a limited
      number of positive tests. Sequencing of 16S DNA displayed the presence of members
      of bacterial genera Bacillus, Halomonas, Pseudomonas, Exiguobacterium and others.
      The genus Bacillus was most commonly identified. None of the isolates were
      members of the Archaea probably due to dilution of salts in the samples.
      CONCLUSIONS: The La Sal del Rey ecosystem supports a robust and diverse bacterial
      community despite the high salinity of the lake and soil. However, salinity does
      appear to a limiting factor with regards to the density and diversity of the
      bacterial communities that inhabit the lake and surrounding area.

PMID- 22480364
TI  - High-resolution mapping of carbene-based protein footprints.
AB  - Carbene chemistry has been used recently in structural mass spectrometry as a
      labeling method for mapping protein surfaces. The current study presents a method
      for quantitating label distribution at the amino acid level and explores the
      nature and basis for an earlier observation of labeling bias. With the use of a
      method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) applied
      to digests of holo-calmodulin, we developed a quantitation strategy to map site
      specific incorporation of carbene, generated from photolysis of ionic label
      precursors 2-amino-4,4-azipentanoic acid and 4,4-azipentanoic acid. The approach
      provides reliable incorporation data for fragments generated by electron-transfer
      dissociation, whereas high-energy collisional dissociation leads to energy and
      sequence-dependent loss of the label as a neutral. However, both can produce data
      suitable for mapping residues in the interaction of holo-calmodulin with M13
      peptide ligand. Site-specific labeling was monitored as a function of reagent,
      ionic strength, and temperature, demonstrating that electrostatic interactions at
      the protein surface can "steer" the distribution of label precursors to sites of
      surface charge and favor label insertion into residues in the vicinity of the
      surface charge. A further preference for insertion into carboxylates was
      observed, based on chemical reactivity. We suggest that decoupling surface
      partitioning from the chemistry of insertion offers a flexible, tunable labeling
      strategy for structural mass spectrometry that can be applied to a broad range of
      protein surface compositions and promotes the design of reagents to simplify the
      workflow.

PMID- 22480363
TI  - Current management of juvenile myelomonocytic leukemia and the impact of RAS
      mutations.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare clonal
      myelodysplastic/myeloproliferative disorder that affects young children. It is
      characterized by hypersensitivity of JMML cells to granulocyte-macrophage colony
      stimulating factor (GM-CSF) in vitro. The pathogenesis of JMML seems to arise
      from constitutional activation of the GM-CSF/RAS (a GTPase) signaling pathway, a
      result of mutations in RAS, NF1, PTPN11, and CBL that interfere with downstream
      components of the pathway. Most patients with JMML usually experience an
      aggressive clinical course, and hematopoietic stem cell transplantation (HSCT) is
      currently the only curative treatment, although the high rates of relapses and
      graft failures are of great concern. In contrast, a certain proportion of
      patients experience a stable clinical course for a considerable period of time,
      and sometimes the disease even spontaneously resolves without any treatment.
      Recent studies have provided us with increased knowledge of genotype-phenotype
      correlations in JMML, and suggested that differences in clinical courses may
      reflect genetic status. Thus, genotype-based management is of current
      international interest, especially for JMML with RAS mutations. Cumulative
      evidence suggests that RAS mutations can be related to favorable clinical
      outcomes, and HSCT may not have to be a mandatory therapeutic option for a
      portion of patients with this mutation, although a consensus regarding genotype
      based management has not yet been achieved. Further efforts toward identifying
      which patients who will do well without HSCT are required.

PMID- 22480365
TI  - Intramolecular vinylation of secondary and tertiary organolithiums.
AB  - Deprotonation of benzylic ureas, carbamates, and thiocarbamates bearing N'
      alkenyl substituents generates carbanions which undergo intramolecular migration
      of the alkenyl group to the carbanionic center. Solvolysis of the urea products
      generates alpha-alkenylated amines. With an enantiomerically pure starting urea,
      migration proceeds stereospecifically, generating in enantiomerically enriched
      form products containing allylic quaternary stereogenic centers bearing N.
      Computational and in situ IR studies suggest that the reaction, formally a
      nucleophilic substitution at an sp(2) carbon atom, proceeds by a concerted
      addition-elimination pathway.

PMID- 22480366
TI  - Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with
      developmental delay and autism spectrum disorders.
AB  - Interstitial deletions of the short arm of chromosome 6 are rare and have been
      associated with developmental delay, hypotonia, congenital anomalies, and
      dysmorphic features. We used array comparative genomic hybridization in a South
      Carolina Autism Project (SCAP) cohort of 97 subjects with autism spectrum
      disorders (ASDs) and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in
      a 15-year-old patient with intellectual disability and ASDs. Subsequent database
      queries revealed five additional individuals with overlapping submicroscopic
      deletions and presenting with developmental and speech delay, seizures,
      behavioral abnormalities, heart defects, and dysmorphic features. The deletion
      found in the SCAP patient harbors ATXN1, DTNBP1, JARID2, and NHLRC1 that we
      propose may be responsible for ASDs and developmental delay.

PMID- 22480367
TI  - Development and application of a liquid chromatography-mass spectrometry method
      to evaluate the glyphosate and aminomethylphosphonic acid dissipation in maize
      plants after foliar treatment.
AB  - A simple and fast method has been developed and validated to measure glyphosate
      (GLYP) and aminomethylphosphonic acid (AMPA), which were previously derivatized
      with 9-fluorenylmethylchloroformate (FMOC-Cl), in maize plants using liquid
      chromatography (LC) coupled to fluorescence (FLD) and electrospray ionization
      mass spectrometry (ESI-MS) detection. The method has shown to be consistent,
      reliable, precise, and efficient. Moreover, the limits of detection (LOD) and
      quantification (LOQ) reached with the proposed method for GLYP and AMPA are lower
      than the established maximum residue levels (MRLs). The validated method was
      applied to quantify GLYP and AMPA in genetically modified (GM) maize foliar
      treated with the herbicide. It has been found that the GLYP dissipation was
      mainly due to the progressive dilution effect after herbicide treatment. Finally,
      it was also observed that the GLYP residue dissipation trend in maize shoot
      (leaves and stem) tissue determined by LC-ESI-MS matched that determined by
      liquid scintillation.

PMID- 22480368
TI  - Divergent total syntheses of (-)-aspidospermine and (+)-spegazzinine.
AB  - Divergent total syntheses of (+)-spegazzinine (1) and (-)-aspidospermine (2) and
      their extensions to the synthesis of C19-epi-aspidospermine and C3-epi
      spegazzinine are detailed, confirming the relative stereochemistry and
      establishing the absolute configuration of (+)-spegazzinine. A powerful
      intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of a 1,3,4-oxadiazole
      provided the pentacyclic skeleton and all the requisite stereochemistry of the
      natural products in a single reaction that forms three rings, four C-C bonds, and
      five stereocenters.

PMID- 22480369
TI  - Biomass pretreatment affects Ustilago maydis in producing itaconic acid.
AB  - BACKGROUND: In the last years, the biotechnological production of platform
      chemicals for fuel components has become a major focus of interest. Although
      ligno-cellulosic material is considered as suitable feedstock, the almost
      inevitable pretreatment of this recalcitrant material may interfere with the
      subsequent fermentation steps. In this study, the fungus Ustilago maydis was used
      to produce itaconic acid as platform chemical for the synthesis of potential
      biofuels such as 3-methyltetrahydrofuran. No studies, however, have investigated
      how pretreatment of ligno-cellulosic biomass precisely influences the subsequent
      fermentation by U. maydis. Thus, this current study aims to first characterize U.
      maydis in shake flasks and then to evaluate the influence of three exemplary
      pretreatment methods on the cultivation and itaconic acid production of this
      fungus. Cellulose enzymatically hydrolysed in seawater and salt-assisted organic
      acid catalysed cellulose were investigated as substrates. Lastly, hydrolysed
      hemicellulose from fractionated beech wood was applied as substrate. RESULTS: U.
      maydis was characterized on shake flask level regarding its itaconic acid
      production on glucose. Nitrogen limitation was shown to be a crucial condition
      for the production of itaconic acid. For itaconic acid concentrations above 25
      g/L, a significant product inhibition was observed. Performing experiments that
      simulated influences of possible pretreatment methods, U. maydis was only
      slightly affected by high osmolarities up to 3.5 osmol/L as well as of 0.1 M
      oxalic acid. The production of itaconic acid was achieved on pretreated cellulose
      in seawater and on the hydrolysed hemicellulosic fraction of pretreated beech
      wood. CONCLUSION: The fungus U. maydis is a promising producer of itaconic acid,
      since it grows as single cells (yeast-like) in submerged cultivations and it is
      extremely robust in high osmotic media and real seawater. Moreover, U. maydis can
      grow on the hemicellulosic fraction of pretreated beech wood. Thereby, this
      fungus combines important advantages of yeasts and filamentous fungi.
      Nevertheless, the biomass pretreatment does indeed affect the subsequent itaconic
      acid production. Although U. maydis is insusceptible to most possible impurities
      from pretreatment, high amounts of salts or residues of organic acids can slow
      microbial growth and decrease the production. Consequently, the pretreatment step
      needs to fit the prerequisites defined by the actual microorganisms applied for
      fermentation.

PMID- 22480371
TI  - Affinity and selectivity of ShK toxin for the Kv1 potassium channels from free
      energy simulations.
AB  - The voltage-gated potassium channel Kv1.3 is an attractive target for treatment
      of autoimmune diseases. ShK toxin from sea anemone is one of the most potent
      blockers of Kv1.3, and therefore ShK and its analogues have been proposed as
      therapeutic leads for such diseases. Increasing the selectivity of the proposed
      leads for Kv1.3 over other Kv1 channels is a major issue in this endeavor. Here
      we study binding of ShK toxin to Kv1 channels using free energy simulation
      methods. Homology models for Kv1.1 and Kv1.3 channels are constructed using the
      crystal structure of Kv1.2. The initial poses for the Kv1.x-ShK complexes are
      obtained using HADDOCK, which are then refined via molecular dynamics
      simulations. The binding mode in each complex is characterized by identifying the
      strongly interacting residues, which compare well with available mutagenesis
      studies. For each complex, the potential of mean force is calculated from
      umbrella sampling simulations, and the corresponding absolute binding free energy
      is determined. The computed binding free energies are in good agreement with the
      experimental data, which increases the confidence on the model complexes. The
      insights gained on Kv1.x-ShK binding modes will be valuable in the development of
      new ShK analogues with better selectivity properties. 

PMID- 22480370
TI  - A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and
      neurotoxicity: relevance to multiple sclerosis.
AB  - BACKGROUND: Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147,
      basigin) is an inducer of the expression of several matrix metalloproteinases
      (MMPs). We reported previously that blocking EMMPRIN activity reduced
      neuroinflammation and severity of disease in an animal model of multiple
      sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). METHODS: To
      improve upon EMMPRIN blockade, and to help unravel the biological functions of
      EMMPRIN in inflammatory disorders, we have developed several anti-EMMPRIN
      monoclonal antibodies. RESULTS: Of these monoclonal antibodies, a particular one,
      clone 10, was efficient in binding mouse and human cells using several methods of
      detection. The specificity of clone 10 was demonstrated by its lack of staining
      of EMMPRIN-null embryos compared to heterozygous and wild-type mouse samples.
      Functionally, human T cells activated with anti-CD3 and anti-CD28 elevated their
      expression of EMMPRIN and the treatment of these T cells with clone 10 resulted
      in decreased proliferation and matrix metalloproteinase- 9 (MMP-9) production.
      Activated human T cells were toxic to human neurons in culture and clone 10
      pretreatment reduced T cell cytotoxicity correspondent with decrease of granzyme
      B levels within T cells. In vivo, EAE mice treated with clone 10 had a markedly
      reduced disease score compared to mice treated with IgM isotype control.
      CONCLUSIONS: We have produced a novel anti-EMMPRIN monoclonal antibody that
      blocks several aspects of T cell activity, thus highlighting the multiple roles
      of EMMPRIN in T cell biology. Moreover, clone 10 reduces EAE scores in mice
      compared to controls, and has activity on human cells, potentially allowing for
      the testing of anti-EMMPRIN treatment not only in EAE, but conceivably also in
      MS.

PMID- 22480372
TI  - Protein-ligand-based pharmacophores: generation and utility assessment in
      computational ligand profiling.
AB  - Ligand profiling is an emerging computational method for predicting the most
      likely targets of a bioactive compound and therefore anticipating adverse
      reactions, side effects and drug repurposing. A few encouraging successes have
      already been reported using ligand 2-D similarity searches and protein-ligand
      docking. The current study describes the use of receptor-ligand-derived
      pharmacophore searches as a tool to link ligands to putative targets. A database
      of 68,056 pharmacophores was first derived from 8,166 high-resolution protein
      ligand complexes. In order to limit the number of queries, a maximum of 10
      pharmacophores was generated for each complex according to their predicted
      selectivity. Pharmacophore search was compared to ligand-centric (2-D and 3-D
      similarity searches) and docking methods in profiling a set of 157 diverse
      ligands against a panel of 2,556 unique targets of known X-ray structure. As
      expected, ligand-based methods outperformed, in most of the cases, structure
      based approaches in ranking the true targets among the top 1% scoring entries.
      However, we could identify ligands for which only a single method was successful.
      Receptor-ligand-based pharmacophore search is notably a fast and reliable
      alternative to docking when few ligand information is available for some targets.
      Overall, the present study suggests that a workflow using the best profiling
      method according to the protein-ligand context is the best strategy to follow. We
      notably present concrete guidelines for selecting the optimal computational
      method according to simple ligand and binding site properties.

PMID- 22480373
TI  - A honey bee (Apis mellifera) light phase response curve.
AB  - The authors report a phase response curve (PRC) for individual honey bees (Apis
      mellifera) to single 1-h light pulses (1000 lux) using an Aschoff Type 1 protocol
      (n = 134). The bee PRC is a weak (Type 1) PRC with a maximum advance of 1.5 h
      between circadian time (CT) 18 and 3 and a maximum delay of 1.5 h between CT 12
      and 18. This is the first published honey bee light PRC and provides an important
      resource for chronobiologists and honey bee researchers. It may also have
      practical applications for what is an economically important species frequently
      transported across different time zones.

PMID- 22480374
TI  - Synthesis and study of the properties of stereocontrolled poly(N
      isopropylacrylamide) gel and its linear homopolymer prepared in the presence of a
      Y(OTf)3 Lewis acid: effect of the composition of methanol-water mixtures as
      synthesis media.
AB  - Poly(N-isopropylacrylamide) (PNIPAM) hydrogels and the corresponding linear
      homopolymers were synthesized in different methanol-water mixtures (x(m) = 0,
      0.13, 0.21, 0.31, 0.43, 0.57, and 0.76, where x(m) is the mole fraction of
      methanol) in the presence of 0.1 M Y(OTf)(3) Lewis acid. The isotacticity (meso
      dyad (m), %) and cloud-point temperature of these homopolymers were gradually
      increased and decreased, respectively, with the increase in the x(m) values of
      the synthesis solvent mixtures. Moreover, the corresponding linear PNIPAM
      homopolymers prepared in the absence of Y(OTf)(3) showed an almost constant
      isotacticity of m = 45% and a cloud-point temperature of 33.0  degrees C. A SEM
      study revealed that the resulting hydrogels were highly porous except for the
      gels prepared at x(m) = 0 and 0.76. The swelling ratios of these hydrogels in
      water at different temperatures and in different methanol-water mixtures at 20 
      degrees C and the deswelling rate and the reswelling rate of these hydrogels were
      studied. All of these swelling results were compared with that of the
      corresponding gels prepared in the absence of a Lewis acid (Biswas, C. S.; Patel,
      V. K.; Vishwakarma, N. K.; Mishra, A. K.; Bhimireddi, R.; Rai, R.; Ray, B. J.
      Appl. Polym. Sci.2012, DOI: 10.1002/app.36318) and explained on the basis of the
      porosity of the gel, the state of aggregation and isotacticity of the PNIPAM
      chain segment, and the cononsolvency of the methanol-water mixture toward the
      PNIPAM chain segment.

PMID- 22480375
TI  - Genetics, environment, and diabetes-related end-stage renal disease in the Canary
      Islands.
AB  - AIMS: Type 1 and type 2 diabetes, complicated with renal disease, have a
      significantly higher incidence in the Canary Islands than in mainland Spain and
      other European countries. Present-day Canarian inhabitants consist of a mixed
      population with North African indigenous and European colonizer ancestors who
      have rapidly evolved from a rural to an urban life style. The aim of this work
      was to assess the possible role of genetic and environmental factors on diabetes
      related end-stage renal disease incidence in the Canary Islands. RESULTS: For
      both types of diabetes there is an ethnic susceptibility increased by diabetes
      family history. Whereas the Y-chromosome does not play a significant role,
      mitochondrial DNA (mtDNA) haplogroup differences point to a maternal origin for
      this ethnic predisposition, confirming susceptible and protective effects for
      haplogroups J and T, respectively. In addition, urban life style seems to be an
      additional risk factor for type 1 diabetes. CONCLUSIONS: The maternal ethnic
      predisposition to diabetes complicated with kidney disease detected in the Canary
      Islands signals mtDNA and X-chromosome markers as the best candidates to uncover
      the genetic predisposition to this disease.

PMID- 22480376
TI  - Use of warfarin in long-term care: a systematic review.
AB  - BACKGROUND: The use of warfarin in older patients requires special consideration
      because of concerns with comorbidities, interacting medications, and the risk of
      bleeding. Several studies have suggested that warfarin may be underused or
      inconsistently prescribed in long-term care (LTC); no published systematic review
      has evaluated warfarin use for stroke prevention in this setting. This review was
      conducted to summarize the body of published original research regarding the use
      of warfarin in the LTC population. METHODS: A systematic literature search of the
      PubMed, Cumulative Index to Nursing and Allied Health Literature, and Cochrane
      Library was conducted from January 1985 to August 2010 to identify studies that
      reported warfarin use in LTC. Studies were grouped by (1) rates of warfarin use
      and prescribing patterns, (2) association of resident and institutional
      characteristics with warfarin prescribing, (3) prescriber attitudes and concerns
      about warfarin use, (4) warfarin management and monitoring, and (5) warfarin
      related adverse events. Summaries of study findings and quality assessments of
      each study were developed. RESULTS: Twenty-two studies met the inclusion criteria
      for this review. Atrial fibrillation (AF) was the most common indication for
      warfarin use in LTC and use of warfarin for stroke survivors was common. Rates of
      warfarin use in AF were low in 5 studies, ranging from 17% to 57%. These usage
      rates were low even among residents with high stroke risk and low bleeding risk.
      Scored bleeding risk had no apparent association with warfarin use in AF. In
      physician surveys, factors associated with not prescribing warfarin included risk
      of falls, dementia, short life expectancy, and history of bleeding. International
      normalized ratio was in the target range approximately half of the time. The
      combined overall rate of warfarin-related adverse events and potential events was
      25.5 per 100 resident months on warfarin therapy. CONCLUSIONS: Among residents
      with AF, use of warfarin and maintenance of INR levels to prevent stroke appear
      to be suboptimal. Among prescribers, perceived challenges associated with
      warfarin therapy often outweigh its benefits. Further research is needed to
      explicitly consider the appropriate balancing of risks and benefits in this frail
      patient population.

PMID- 22480377
TI  - "Tell me what you want, what you really really want....": asking people with
      multiple sclerosis about enhancing their participation in physical activity.
AB  - PURPOSE: This paper provides a review of research that emphasizes the importance
      of listening to the people whom health professionals serve when promoting
      participation and engagement in rehabilitation. We report on the development of
      an approach aiming to optimize long-term adherence in physical activity for
      people with multiple sclerosis (MS). This approach was very different to those
      based on current evidence-based exercise recommendations, although the objectives
      for both approaches were similar. KEY MESSAGE: We argue that only by ensuring
      that people living with chronic disability not only have a voice but a voice that
      is listened to, can health professionals truly engage in evidenced-based practice
      that works in application and meets the needs, desires and capabilities of people
      with MS and other chronic health conditions.

PMID- 22480378
TI  - Antioxidant properties of Taraxacum officinale fruit extract are involved in the
      protective effect against cellular death induced by sodium nitroprusside in brain
      of rats.
AB  - CONTEXT: Taraxacum officinale Weber (Asteraceae), known as dandelion, is used for
      medicinal purposes due to its choleretic, diuretic, antitumor, antioxidant,
      antiinflammatory, and hepatoprotective properties. OBJECTIVE: We sought to
      investigate the protective activity of T. officinale fruit extract against sodium
      nitroprusside (SNP)-induced decreased cellular viability and increased lipid
      peroxidation in the cortex, hippocampus, and striatum of rats in vitro. To
      explain the mechanism of the extract's antioxidant activity, its putative
      scavenger activities against NO, DPPH., OH., and H(2)O(2) were determined.
      METHODS: Slices of cortex, hippocampus, and striatum were treated with 50 MUM SNP
      and T. officinale fruit ethanolic extract (1-20 ug/mL) to determine cellular
      viability by MTT reduction assay. Lipid peroxidation was measure in cortical,
      hippocampal and striatal slices incubates with SNP (5 uM) and T. officinale fruit
      extract (1-20 ug/mL). We also determined the scavenger activities of T.
      officinale fruit extract against NO., DPPH., OH., and H(2)O(2), as well as its
      iron chelating capacity. RESULTS: The extract (1, 5, 10, and 20 MUg/mL) protected
      against SNP-induced decreases in cellular viability and increases in lipid
      peroxidation in the cortex, hippocampus, and striatum of rats. The extract had
      scavenger activity against DPPH. and NO. at low concentrations and was able to
      protect against H(2)O(2) and Fe(2+)-induced deoxyribose oxidation. CONCLUSION: T.
      officinale fruit extract has antioxidant activity and protects brain slices
      against SNP-induced cellular death. Possible mechanisms of action include its
      scavenger activities against reactive oxygen species (ROS) and reactive nitrogen
      species (RNS), which are attributed to the presence of phenolic compounds in the
      extract.

PMID- 22480379
TI  - Loss of trophic complexity in saline prairie lakes as indicated by stable-isotope
      based community-metrics.
AB  - Variations in climate, watershed characteristics and lake-internal processes
      often result in a large variability of food-web complexity in lake ecosystems.
      Some of the largest ranges in these environmental parameters can be found in
      lakes across the northern Great Plains as they are characterized by extreme
      gradients in respect to lake morphometry and water chemistry, with individual
      parameters often varying over several orders of magnitude. To evaluate the
      effects of environmental conditions on trophic complexity in prairie lake food
      webs, we analyzed carbon and nitrogen stable isotopes of fishes, zooplankton and
      littoral macroinvertebrates in 20 lakes across southern Saskatchewan. Our two
      year study identified very diverse patterns of trophic complexity, with was
      predominantly associated with among-lake differences. Small but significant
      temporal effects were also detected, which were predominantly associated with
      changes in productivity. The most influential parameters related to changes in
      trophic complexity among lakes were salinity, complexity of fish assemblage, and
      indicators of productivity (e.g. nutrients, Chl a). Generally, trophic diversity,
      number of trophic levels, and trophic redundancy were highest in productive
      freshwater lakes with diverse fish communities. Surprisingly, mesosaline lakes
      that were characterized by very low or no predation pressure from fishes were not
      colonized by invertebrate predators as it is often the case in boreal systems;
      instead, trophic complexity was further reduced. Together, prairie lake food-webs
      appear to be highly sensitive to changes in salinity and the loss of piscivorous
      fishes, making freshwater and mesosaline lakes most vulnerable to the impacts of
      climate variability. This is particularly important as global circulation models
      predict future climate warming to have disproportionate negative impacts on
      hydrologic conditions in this area.

PMID- 22480382
TI  - Synthesis of heterocyclic [3.3.3]propellanes via a sequential four-component
      reaction.
AB  - A highly chemoselective heteroannulation protocol for the synthesis of unreported
      polysubstituted heterocyclic [3.3.3]propellanes has been developed by sequential
      four-component reaction of ninhydrin, malononitrile, primary amines, and dialkyl
      acetylenedicarboxylates under mild conditions in water. To the best of our
      knowledge, there are no previous reports for the synthesis of these classes of
      heterocyclic [3.3.3]propellanes. The merit of this sequential Knoevenagel
      condensation/enamine formation/Michael addition/cyclization sequence is
      highlighted by its high atom-economy, excellent yields, the use of water as
      reaction media, and the efficiency of production without the use of any activator
      or metal promoters. This synthesis serves as a nice addition to group-assistant
      purification (GAP) chemistry in which purification via chromatography and
      recrystallization can be avoided, and the pure products were obtained simply by
      washing the crude products with 95% ethanol.

PMID- 22480381
TI  - Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic
      purpura: a NICE single technology appraisal.
AB  - The National Institute for Health and Clinical Excellence (NICE) invited the
      manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical
      and cost effectiveness of this drug for the treatment of patients with chronic
      immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single
      Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review
      (TAR) Group, commissioned to act as the evidence review group (ERG), critically
      reviewed and supplemented the submitted evidence. This paper describes the
      company submission, the ERG review and NICE's subsequent decisions. The ERG
      critically appraised the clinical and cost-effectiveness evidence submitted by
      the manufacturer, independently searched for relevant literature, conducted a
      critical appraisal of the submitted economic models and explored the impact of
      altering some of the key model assumptions as well as combining relevant
      sensitivity analyses. Three trials were used to inform the safety and efficacy
      aspects of this submission; however, one high-quality randomized controlled trial
      (RAISE study) was the principal source of evidence and was used to inform the
      economic model. Eltrombopag had greater odds of achieving the primary outcome of
      a platelet count between 50 * 10^9/L and 400 * 10^9/L during the 6-month
      treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the
      eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of
      splenectomized patients achieved this outcome. The median duration of response
      was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4)
      compared with 0 for placebo. Eltrombopag patients required less rescue medication
      and had lower odds of bleeding events for both the splenectomized and the non
      splenectomized patients. For a watch-and-rescue strategy of care, the comparator
      was placebo and the ERG found that substantial reductions in the cost of
      eltrombopag are needed before the incremental cost per QALY is less than L30,000.
      There was significant uncertainty, with the incremental cost-effectiveness ratio
      (ICER) reported varying from L33,561 to L103,500 per QALY (splenectomized) and
      L39,657 to L150,245 per QALY (non-splenectomized). All costs are presented in L,
      year 2008 values, as this was the costing year for the manufacturer's model.
      Other than bleeding, no adverse events were modelled. In relation to the long
      term treatment model, the ERG questioned the robustness of the use of non
      randomized non-comparative data. The base-case results restricting the time
      horizon to 2 years and prescribing eltrombopag as second-line treatment post
      rituximab were found to be favourable towards eltrombopag. As rituximab is not a
      licensed treatment for ITP, the ERG were concerned that its inclusion may not be
      reflective of clinical practice. None of the treatment sequences resulted in an
      ICER approaching the recommended threshold of L30,000 per QALY gained.
      Eltrombopag appears to be a safe treatment for ITP (although long-term follow-up
      studies are awaited) and has short-term efficacy. However, NICE found based on
      the evidence submitted and reviewed that there was no robust evidence on the long
      term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence
      for eltrombopag tested against other relevant comparators.

PMID- 22480380
TI  - Infrared multiphoton dissociation for quantitative shotgun proteomics.
AB  - We modified a dual-cell linear ion trap mass spectrometer to perform infrared
      multiphoton dissociation (IRMPD) in the low-pressure trap of a dual-cell
      quadrupole linear ion trap (dual-cell QLT) and perform large-scale IRMPD analyses
      of complex peptide mixtures. Upon optimization of activation parameters
      (precursor q-value, irradiation time, and photon flux), IRMPD subtly, but
      significantly, outperforms resonant-excitation collisional-activated dissociation
      (CAD) for peptides identified at a 1% false-discovery rate (FDR) from a yeast
      tryptic digest (95% confidence, p = 0.019). We further demonstrate that IRMPD is
      compatible with the analysis of isobaric-tagged peptides. Using fixed QLT rf
      amplitude allows for the consistent retention of reporter ions, but necessitates
      the use of variable IRMPD irradiation times, dependent upon precursor mass to
      charge (m/z). We show that IRMPD activation parameters can be tuned to allow for
      effective peptide identification and quantitation simultaneously. We thus
      conclude that IRMPD performed in a dual-cell ion trap is an effective option for
      the large-scale analysis of both unmodified and isobaric-tagged peptides.

PMID- 22480383
TI  - Separation and characterization of acetyl and non-acetyl hemicelluloses of Arundo
      donax by ammonium sulfate precipitation.
AB  - Delignified  Arundo donax  was sequentially extracted with DMSO, saturated barium
      hydroxide, and 1.0 M aqueous NaOH solution. The yields of the soluble fractions
      were 10.2, 6.7, and 10.0% (w/w), respectively, of the dry  Arundo donax 
      materials. The DMSO-, Ba(OH)(2)- and NaOH-soluble hemicellulosic fractions were
      further fractionated into two subfractions by gradient 50% and 80% saturation
      ammonium sulfate precipitation, respectively. Monosaccharide, molecular weight,
      FT-IR, and 1D ((1)H and (13)C) and 2D (HSQC) NMR analysis revealed the
      differences in structural characteristics and physicochemical properties among
      the subfractions. The subfractions precipitated with 50% saturation ammonium
      sulfate had lower arabinose/xylose and glucuronic acid/xylose ratios but had
      higher molecular weight than those of the subfractions precipitated by 80%
      saturation ammonium sulfate. FT-IR and NMR analysis revealed that the highly
      acetylated DMSO-soluble hemicellulosic subfraction (H(D50)) could be precipitated
      with a relatively lower concentration of 50% saturated ammonium sulfate, and thus
      the gradient ammonium sulfate precipitation technique could discriminate acetyl
      and non-acetyl hemicelluloses. It was found that the DMSO-soluble subfraction
      H(D50) precipitated by 50% saturated ammonium sulfate mainly consisted of poorly
      substituted O-acetyl arabino-4-O-methylglucurono xylan with terminal units of
      arabinose linked on position 3 of xylose, 4-O-methylglucuronic acid residues
      linked on position 2 of the xylan bone, and the acetyl groups (degree of
      acetylation, 37%) linked on position 2 or 3. The DMSO-soluble subfraction H(D80)
      precipitated by 80% saturated ammonium sulfate was mainly composed of highly
      substituted arabino-4-O-methylglucurono xylan and beta-d-glucan.

PMID- 22480385
TI  - DNA fragments binding CTCF in vitro and in vivo are capable of blocking enhancer
      activity.
AB  - BACKGROUND: Earlier we identified ten 100-300-bp long CTCF-binding DNA fragments
      selected earlier from a 1-Mb human chromosome 19 region. Here the positive
      negative selection technique was used to check the ability of CTCF-binding human
      genomic fragments to block enhancer-promoter interaction when inserted into the
      genome. RESULTS: Ten CTCF-binding DNA fragments were inserted between the CMV
      enhancer and CMV minimal promoter driving the herpes simplex virus thymidine
      kinase (HSV-tk) gene in a vector expressing also the neoR gene under a separate
      promoter. The constructs were then integrated into the genome of CHO cells, and
      the cells resistant to neomycin and ganciclovir (positive-negative selection)
      were picked up, and their DNAs were PCR analyzed to confirm the presence of the
      fragments between the enhancer and promoter in both orientations. CONCLUSIONS: We
      demonstrated that all sequences identified by their CTCF binding both in vitro
      and in vivo had enhancer-blocking activity when inserted between the CMV minimal
      promoter and enhancer in stably transfected CHO cells.

PMID- 22480387
TI  - Association of common variations in the norepinephrine transporter gene with
      response to olanzapine-fluoxetine combination versus continued-fluoxetine
      treatment in patients with treatment-resistant depression: a candidate gene
      analysis.
AB  - OBJECTIVE: To determine whether single-nucleotide polymorphisms (SNPs) in
      candidate genes are associated with response to olanzapine-fluoxetine
      combination. METHOD: A post hoc analysis of a priori-selected SNPs used data from
      a clinical trial (dates: April 2002-July 2005) of olanzapine-fluoxetine
      combination, fluoxetine, and olanzapine in patients with major depressive
      disorder (DSM-IV criteria) and with nonresponse to prestudy antidepressant
      treatment and nonresponse to fluoxetine treatment during the study. Patients
      received open-label treatment with fluoxetine for 8 weeks (2 weeks, 25 mg/d; then
      6 weeks, 50 mg/d), at the end of which nonresponders (< 25% decline in the 17
      item Hamilton Depression Rating Scale score) were randomized to receive double
      blind, monotherapy treatment with olanzapine-fluoxetine combination (6/50-18/50
      mg/d, n = 71), fluoxetine (50 mg/d, n = 78), or olanzapine (6-18 mg/d, n = 56)
      for 8 weeks. Statistical significance was assessed at P < .05. The primary
      efficacy measure for within-study treatment was improvement on the Montgomery
      Asberg Depression Rating Scale (MADRS). RESULTS: Rs36024, an intronic SNP in the
      norepinephrine transporter (SLC6A2), as well as 3 SNPs in melanocortin 3 receptor
      (MC3R) and 2 SNPs in tryptophan hydroxylase 2 (TPH2), were associated with MADRS
      defined response to treatment with olanzapine-fluoxetine combination (adjusted Li
      Nyholt P < .05). Except for 1 SNP in TPH2, identified SNPs were not significantly
      associated with response to continued-fluoxetine or olanzapine treatments.
      CONCLUSIONS: Our findings further support the hypothesis that the synergistic
      effect of olanzapine and fluoxetine on prefrontal cortical levels of
      norepinephrine and dopamine might be an underlying mechanism for the efficacy of
      olanzapine-fluoxetine combination in the treatment of treatment-resistant
      depression and, if replicated, may form a basis on which response to olanzapine
      fluoxetine combination versus continued fluoxetine can be predicted based on
      variants in SLC6A2. TRIAL REGISTRATION: Parent study registered at
      ClinicalTrials.gov identifier: NCT00035321.

PMID- 22480388
TI  - Cationic Ir(III) alkylidenes are key intermediates in C-H bond activation and C-C
      bond-forming reactions.
AB  - This work describes the chemical reactivity of a cationic (eta(5)
      C(5)Me(5))Ir(III) complex that contains a bis(aryl) phosphine ligand, whose
      metalation determines its unusual coordination in a kappa(4)-P,C,C',C" fashion.
      The complex (1(+) in this paper) undergoes very facile intramolecular C-H bond
      activation of all benzylic sites, in all likelihood through an Ir(V) hydride
      intermediate. But most importantly, it transforms into a hydride phosphepine
      species 4(+) by means of an also facile, base-catalyzed, intramolecular
      dehydrogenative C-C coupling reaction. Mechanistic studies demonstrate the
      participation as a key intermediate of an electrophilic cationic Ir(III)
      alkylidene, which has been characterized by low-temperature NMR spectroscopy and
      by isolation of its trimethylphosphonium ylide. DFT calculations provide
      theoretical support for these results.

PMID- 22480389
TI  - Enhancing the fouling resistance of biocidal urethane coatings via surface
      chemistry modulation.
AB  - A group of novel cross-linked polyurethane materials with varying ratios of
      hydroxyl-terminated macrodiols and tethered quaternary ammonium biocides have
      been prepared. The resulting materials had a wide range of thermal, mechanical,
      and surface properties, dictated by the macrodiol composition and biocide
      concentration. The complex interplay between surface chemistry and biocide
      concentration was shown to have a profound effect on the fouling resistance of
      these materials. While the combination of quaternary ammonium salt (QAS) diols
      with poly(tetramethylene oxide) macrodiols did not result in any enhancement of
      fouling resistance,  addition of biocides to poly(ethylene glycol)-containing
      urethanes resulted in up to a 90% increase in biocidal activity compared to
      control materials while reducing the ability for microbes to adhere to the
      surface by an additional 60%. Materials prepared with polybutadiene macrodiols
      underwent a thermally induced oxidation, resulting in partial decomposition of
      the quaternary ammonium salt biocide and joint antimicrobial activity arising
      from remaining QAS and peroxide compounds.

PMID- 22480390
TI  - Prognostic relevance of Id-1 expression in patients with resectable esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Inhibitor of differentiation or DNA binding 1 (Id-1) is a
      transcriptional regulator that is associated with enhanced malignant potential
      and unfavorable survival in many cancers. However, its role and clinical
      significance in resectable esophageal squamous cell carcinoma (ESCC) has not been
      elucidated adequately. The purpose of this study was to explore the pattern of Id
      1 expression and analyze its correlation with clinical outcomes of patients with
      resectable ESCC. METHODS: Primary tumors from 407 surgically resected ESCC
      specimens assembled on tissue microarrays were evaluated with immunohistochemical
      analysis for Id-1. The effect of Id-1 expression on survival outcome was analyzed
      by the Kaplan-Meier method. RESULTS: The expression of Id-1 correlated closely
      with pT category (p<0.001), pathologic staging (p<0.001), and pN category
      (p<0.001). The sensitivity, specificity, and accuracy of predicting lymph node
      metastasis by Id-1 expression were 93.3%, 94.7%, and 94.1%, respectively. Disease
      specific survival was significantly favorable in patients with low-level Id-1
      expression (p<0.001). Overexpression of Id-1 was also effective to predict
      unfavorable survival in subgroups of patients with poor differentiation (p<0.001)
      or with advanced T staging (p<0.001). Multivariate analysis showed that the level
      of Id-1 expression was an independent prognostic factor in ESCC (p<0.001;
      relative risk, 1.578). CONCLUSIONS: Expression of Id-1 can be used as a
      complement for predicting lymph node metastasis in pretreatment workup. High
      level of Id-1 expression suggested unfavorable prognosis for patients with
      resectable ESCC.

PMID- 22480391
TI  - Model for end-stage liver disease score predicts adverse events related to
      ventricular assist device therapy.
AB  - BACKGROUND: The Model for End-stage Liver Disease (MELD) score is a marker of
      multisystem organ dysfunction. It has been used to predict outcomes in patients
      undergoing hepatic and nonhepatic interventions. End-stage heart disease exhibits
      a varying degree of multiorgan dysfunction, which impacts the adverse events
      related to ventricular assist device (VAD) therapy. Our aim for the present study
      was to investigate the value of MELD score in predicting adverse events related
      with VAD therapy. METHODS: Data were collected on demographics, clinical
      characteristics, MELD score; Interagency Registry for Mechanically Assisted
      Circulatory Support-defined VAD adverse events within the first 6 months, and
      survival from VAD recipients (n=286; from 1996 to 2009). Univariable,
      multivariable, and Cox regression analyses were performed using SAS software (SAS
      Institute, Cary, NC). RESULTS: The mean MELD score was 14.4+/-5.9. Actuarial
      incidence of infections, bleeding events, and cardiovascular dysfunction at 6
      months was 65.4%, 52.1%, and 45.6%, respectively. Multivariable Cox proportional
      hazards model (controlling for gender, type of device, diagnosis, intention to
      treat, urgency, and inotropic use) confirmed that MELD score predicted mortality,
      respiratory, and renal dysfunction at 6 months (p<0.01). CONCLUSIONS:
      Preoperative MELD score is predictive of mortality, respiratory, and renal
      dysfunction at 6 months after controlling for gender, type of device, diagnosis,
      intention to treat, urgency, and inotropic use. The MELD score may be used as a
      quantitative tool to assess the adverse events associated with VAD therapy.

PMID- 22480392
TI  - Completeness of revascularization and survival among octogenarians with triple
      vessel disease.
AB  - BACKGROUND: We sought to determine the impact of the completeness of surgical
      revascularization among octogenarians with triple-vessel disease. METHODS:
      Between 1992 and 2008, 476 consecutive patients aged 80 years or more who
      underwent primary isolated coronary artery bypass grafting (CABG) procedures were
      identified. Early and late survival were compared among patients who underwent
      complete revascularization (CR, n=391) and incomplete revascularization (IR,
      n=85). IR was present when 1 or more of the 3 main coronary arteries with 50% or
      greater stenosis that were identified preoperatively as a surgical target by the
      operating surgeon were not grafted. The mean follow-up was 5.4+/-3.0 years
      (maximum 15.3 years). RESULTS: Baseline risk was similar between the 2 groups of
      patients. IR was more frequent in off-pump compared with on-pump CABG (34.9%
      versus 16.2%, respectively; p=0.002). The most common reason for IR was small or
      severely diseased arteries (87%). The incidence of postoperative myocardial
      infarction (MI) was similar in both groups (CR, 18.4% versus IR, 17.3%; p=0.81).
      In-hospital mortality was 7.2% among patients with CR and 4.7% among patients
      with IR (p=0.60). Three, 5-, and 8-year freedom from all-cause mortality among
      patients who underwent CR were 89.2%, 74.1%, and 54.3%, respectively, and were
      not significantly different from those patients who underwent IR (86.6%, 74.5%,
      and 49.4%, respectively) (p=0.40). CONCLUSIONS: In octogenarians with triple
      vessel disease, a strategy of incomplete revascularization during CABG does not
      negatively impact early or long-term survival.

PMID- 22480393
TI  - What is the best strategy for brain protection in patients undergoing aortic arch
      surgery? A single center experience of 636 patients.
AB  - BACKGROUND: Cerebral protection during aortic arch surgery can be performed using
      various surgical strategies. We retrospectively analyzed our results of different
      brain protection modalities during aortic arch surgery. METHODS: Between January
      2003 and November 2009, 636 consecutive patients underwent aortic arch
      replacement surgery using unilateral antegrade cerebral perfusion (UACP [n=123]),
      bilateral antegrade cerebral perfusion (BACP [n=242]), retrograde cerebral
      perfusion (RCP [n=51]), or deep hypothermia and circulatory arrest (DHCA
      [n=220]). Mean age of patients was 62+/-14 years, 64% were male, 15% were
      reoperations, and 37% were performed for acute type A dissections. Mean follow-up
      was 4.9+/-0.1 years and was 97% complete. RESULTS: Circulatory arrest time was
      22+/-17 minutes UACP, 23+/-21 minutes BACP, 18+/-12 minutes RCP, and 15+/-13
      minutes DHCA; p<0.001). Early mortality was 11% (n=72) and was not different
      between the surgical groups. Stroke rate was 9% for ACP patients (n=33) versus
      15% (n=39) for patients who did not receive ACP (p=0.035). Independent predictors
      of stroke were type A aortic dissection (odds ratio [OR], 1.9; 95% confidence
      interval [CI], 1.3 to 3.2; p<0.001), age (OR, 1.04; 95% CI, 1.01 to 1.06;
      p=0.001), duration of circulatory arrest (OR, 1.01, 95% CI, 1.002 to 1.03;
      p=0.02), and total aortic arch replacement (OR, 2.7; 95% CI, 1.3 to 5.7;
      p=0.005). Five year survival was 68%+/-4% and was not significantly different
      between groups. CONCLUSIONS: Antegrade cerebral perfusion is associated with
      significantly less neurologic complications than RCP and DHCA, despite longer
      circulatory arrest times. Medium-term survival is worse for patients with
      postoperative permanent neurologic deficit and preoperative type A aortic
      dissection.

PMID- 22480394
TI  - Induction therapy followed by surgery for T3-T4/N0 non-small cell lung cancer:
      long-term results.
AB  - BACKGROUND: The aim of this study was to analyze the impact of the induction
      chemoradiotherapy (IT) on the survival pattern in T3/T4-N0 non-small cell lung
      cancer (NSCLC) patients. METHODS: The data of 71 patients treated from January
      1992 to May 2007 were reviewed. Of these, 31 patients received IT prior to
      surgery (IT group: T3, 20 patients; and T4, 11 patients), and 40 directly
      underwent surgery (S group: T3, 34 patients; and T4, 6 patients). Survival rates
      were compared using the Kaplan-Meier analysis and the Cox proportional hazards
      models. RESULTS: Mean ages were 62.5+/-9.9 years in the IT group and 67.7+/-7.1
      in the S group. All patients but 1 completed the IT treatment and 27 patients
      (87%) were operated. A radical resection was possible in 21 patients (78%). In
      the IT group a complete pathologic response was obtained in 6 patients (22%),
      where 8 patients ended up in pI stage, 7 in pII stage, and 6 in pIII stage. The
      overall 5-year survival (long-term survival [LTS]) and disease-free 5-year
      survival (DFS) for the entire cohort were 40% and 34%, respectively. No
      significant differences were found when LTS in the IT group (44%) and in the S
      group (37%) were compared. At multivariate analysis, the completeness of
      resection was the only independent predictive factor (hazard ratio [HR]=5.18; 95%
      confidence interval [CI]=2.55 to 10.28) while Cox multivariate analysis (on the
      IT group only) confirmed the critical role of the pathologic downstaging
      (HR=4.62; 95% CI=1.54 to 13.89). CONCLUSIONS: A multimodal strategy with IT
      treatment followed by surgery is a safe and reasonable treatment in T3/T4-N0
      NSCLC patients, but no clear evidence of prognostic improvement may be assumed at
      the present time. Nevertheless, patients with radical resection and complete
      pathologic response have a very rewarding survival.

PMID- 22480395
TI  - Systems analysis of inflammatory bowel disease based on comprehensive gene
      information.
AB  - BACKGROUND: The rise of systems biology and availability of highly curated gene
      and molecular information resources has promoted a comprehensive approach to
      study disease as the cumulative deleterious function of a collection of
      individual genes and networks of molecules acting in concert. These "human
      disease networks" (HDN) have revealed novel candidate genes and pharmaceutical
      targets for many diseases and identified fundamental HDN features conserved
      across diseases. A network-based analysis is particularly vital for a study on
      polygenic diseases where many interactions between molecules should be
      simultaneously examined and elucidated. We employ a new knowledge driven HDN gene
      and molecular database systems approach to analyze Inflammatory Bowel Disease
      (IBD), whose pathogenesis remains largely unknown. METHODS AND RESULTS: Based on
      drug indications for IBD, we determined sibling diseases of mild and severe
      states of IBD. Approximately 1,000 genes associated with the sibling diseases
      were retrieved from four databases. After ranking the genes by the frequency of
      records in the databases, we obtained 250 and 253 genes highly associated with
      the mild and severe IBD states, respectively. We then calculated functional
      similarities of these genes with known drug targets and examined and presented
      their interactions as PPI networks. CONCLUSIONS: The results demonstrate that
      this knowledge-based systems approach, predicated on functionally similar genes
      important to sibling diseases is an effective method to identify important
      components of the IBD human disease network. Our approach elucidates a previously
      unknown biological distinction between mild and severe IBD states.

PMID- 22480396
TI  - Comparative quantitative proteomics of prochlorococcus ecotypes to a decrease in
      environmental phosphate concentrations.
AB  - BACKGROUND: The well-lit surface waters of oligotrophic gyres significantly
      contribute to global primary production. Marine cyanobacteria of the genus
      Prochlorococcus are a major fraction of photosynthetic organisms within these
      areas. Labile phosphate is considered a limiting nutrient in some oligotrophic
      regions such as the Caribbean Sea, and as such it is crucial to understand the
      physiological response of primary producers such as Prochlorococcus to
      fluctuations in the availability of this critical nutrient. RESULTS:
      Prochlorococcus strains representing both high light (HL) (MIT9312) and low light
      (LL) (NATL2A and SS120) ecotypes were grown identically in phosphate depleted
      media (10 MUM Pi). The three strains displayed marked differences in cellular
      protein expression, as determined by high throughput large scale quantitative
      proteomic analysis. The only strain to demonstrate a significantly different
      growth rate under reduced phosphate conditions was MIT9312. Additionally, there
      was a significant increase in phosphate-related proteins such as PhoE (> 15 fold
      increase) and a depression of the Rubisco protein RbcL abundance in this strain,
      whereas there appeared to be no significant change within the LL strain SS120.
      CONCLUSIONS: This differential response between ecotypes highlights the relative
      importance of phosphate availability to each strain and from these results we
      draw the conclusion that the expression of phosphate acquisition mechanisms are
      activated at strain specific phosphate concentrations.

PMID- 22480397
TI  - Study of nano-emulsion formation by dilution of microemulsions.
AB  - The influence of different dilution procedures on the properties of oil-in-water
      (O/W) nano-emulsions obtained by dilution of oil-in-water (O/W) and water-in-oil
      (W/O) microemulsions has been studied. The system water/SDS/cosurfactant/dodecane
      with either hexanol or pentanol as cosurfactant was chosen as model system. The
      dilution procedures consisted of adding water (or microemulsion) stepwise or at
      once over a microemulsion (or water). Starting emulsification from O/W
      microemulsions, nano-emulsions with droplet diameters of 20 nm are obtained,
      independently on the microemulsion composition and the dilution procedure used.
      In contrast, starting emulsification from W/O microemulsions, nano-emulsions are
      only obtained if the emulsification conditions allow reaching the equilibrium in
      an O/W microemulsion domain during the process. These conditions are achieved by
      stepwise addition of water over W/O microemulsions with O/S ratios at which a
      direct microemulsion domain is crossed during emulsification. The nature of the
      alcohol used as cosurfactant has been found to play a key role on the properties
      of the nano-emulsions obtained: nano-emulsions in the system using hexanol as
      cosurfactant are smaller in size, lower in polydispersity, and have a higher
      stability than those with pentanol.

PMID- 22480398
TI  - One-pot aqueous phase growth of biocompatible 15-130 nm gold nanoparticles
      stabilized with bidentate PEG.
AB  - We describe a new, single pot, aqueous phase method for synthesizing water
      soluble gold nanoparticles (AuNPs) over a size range of 15-130 nm. Poly(ethylene
      glycol)-appended thioctic acid ligands were used to control the growth rates and
      stabilize the AuNPs. Critical factors that enable the controlled growth of the
      AuNPs over this size range include the pH, the choice of reducing agent, the
      reaction temperature and the sequential addition of gold precursor and ligand
      with specific ligand-to-gold ratios. We describe the synthetic procedure in
      detail. Optical and structural characterization of the AuNPs was accomplished
      using UV-vis absorption spectroscopy, dynamic light scattering, and transmission
      and scanning electron microscopy.

PMID- 22480399
TI  - End-to-end assembly of gold nanorods via oligopeptide linking and surfactant
      control.
AB  - We report two novel approaches for fabricating self-assembled chains of end-to
      end linked Au nanorods separated by a nanogap. In one approach, bi-functional
      cysteine end-capped oligopeptides of different lengths are used as the linking
      agent. The widths of the produced nanogaps scale with the length and tertiary
      structure of the peptide linker. Functionalized oligopeptides containing an
      acetylene group are also employed as a linker, and the functional group is
      uniquely identified using surface-enhanced Raman spectroscopy. The development of
      an oligopeptide-linking platform is motivated by the ease of synthesis and high
      modularity of peptides; these features enable the possibility to integrate
      diverse functionality into molecular nanogap junctions - synthesized in water.
      The stepwise nanochain formation is followed via the evolution of the
      longitudinal plasmon absorption band in combination with transmission electron
      microscopy. The reaction rate and extent is tuned by controlling the
      concentration of the stabilizing CTAB surfactant in the solution. At very low
      surfactant concentrations, spontaneous end-to-end linking of the Au nanorods is
      observed even in the absence of linking peptide. The assembled AuNRs may act as
      next-generation electrodes in a platform for molecular electronics and synthetic
      biology.

PMID- 22480400
TI  - Interfacial layers from the protein HFBII hydrophobin: dynamic surface tension,
      dilatational elasticity and relaxation times.
AB  - The pendant-drop method (with drop-shape analysis) and Langmuir trough are
      applied to investigate the characteristic relaxation times and elasticity of
      interfacial layers from the protein HFBII hydrophobin. Such layers undergo a
      transition from fluid to elastic solid films. The transition is detected as an
      increase in the error of the fit of the pendant-drop profile by means of the
      Laplace equation of capillarity. The relaxation of surface tension after
      interfacial expansion follows an exponential-decay law, which indicates
      adsorption kinetics under barrier control. The experimental data for the
      relaxation time suggest that the adsorption rate is determined by the balance of
      two opposing factors: (i) the barrier to detachment of protein molecules from
      bulk aggregates and (ii) the attraction of the detached molecules by the
      adsorption layer due to the hydrophobic surface force. The hydrophobic attraction
      can explain why a greater surface coverage leads to a faster adsorption. The
      relaxation of surface tension after interfacial compression follows a different,
      square-root law. Such behavior can be attributed to surface diffusion of adsorbed
      protein molecules that are condensing at the periphery of interfacial protein
      aggregates. The surface dilatational elasticity, E, is determined in experiments
      on quick expansion or compression of the interfacial protein layers. At lower
      surface pressures (<11 mN/m) the experiments on expansion, compression and
      oscillations give close values of E that are increasing with the rise of surface
      pressure. At higher surface pressures, E exhibits the opposite tendency and the
      data are scattered. The latter behavior can be explained with a two-dimensional
      condensation of adsorbed protein molecules at the higher surface pressures. The
      results could be important for the understanding and control of dynamic processes
      in foams and emulsions stabilized by hydrophobins, as well as for the
      modification of solid surfaces by adsorption of such proteins.

PMID- 22480401
TI  - Thermo-responsive monodisperse core-shell microspheres with PNIPAM core and
      biocompatible porous ethyl cellulose shell embedded with PNIPAM gates.
AB  - Monodisperse microspheres composed of thermo-responsive poly(N
      isopropylacrylamide) (PNIPAM) core and biocompatible porous ethyl cellulose (EC)
      shell embedded with PNIPAM gates have been successfully prepared by microfluidic
      emulsification, solvent evaporation and free radical polymerization. Attributing
      to the coating of EC shell, the mechanical strength and biocompatibility of the
      core-shell microsphere are much better than those of the PNIPAM core itself.
      Fourier transform infrared (FT-IR) spectrometer and scanning electron microscopy
      (SEM) are employed to examine chemical compositions and microstructures of
      prepared microparticles. By the cooperative action of EC shell with PNIPAM gates
      and PNIPAM core, the proposed core-shell microspheres exhibit satisfactory thermo
      responsive controlled release behaviors of model drug molecules rhodamine B (Rd
      B) and VB12. At temperatures above the volume phase transition temperature (VPTT)
      of PNIPAM, the release rate of solute molecules is much faster than that at
      temperatures below the VPTT. The controlled factor of the prepared core-shell
      microspheres for VB12 release reaches to as high as 11.7. The proposed
      microspheres are highly attractive for controlled drug delivery.

PMID- 22480402
TI  - Oculomotor deficits affect neuropsychological performance in oculomotor apraxia
      type 2.
AB  - INTRODUCTION: Ataxia with oculomotor apraxia type 2 is a rare and early-disabling
      neurodegenerative disease, part of a subgroup of autosomal recessive cerebellar
      ataxia, in which oculomotor symptoms (e.g., increased saccade latency and
      hypometria) and executive function deficits have been described. The aim of this
      study was to evaluate the impact of oculomotor symptoms on cognitive performance
      and, in particular, over reading in 2 Italian siblings affected by ataxia with
      oculomotor apraxia type 2. METHODS: The neuropsychological profiles and the
      oculomotor patterns during nonverbal and verbal tasks were recorded and analyzed.
      RESULTS: Saccadic intrusions and/or nystagmus were observed in all eye movement
      tasks. The neuropsychological profiles were substantially preserved, with only
      subtle deficits that affected visuomotor integration and attention. Reading
      ability decreased and became impaired. The reading scan was disturbed by saccadic
      intrusions and/or nystagmus. However, an ad hoc reading task demonstrated that
      deficits appeared only when the items that were displayed enhanced oculomotor
      requests. The preservation of lexical-semantic processes confirmed that the
      reading disability was caused by oculomotor deficits, not cognitive problems.
      CONCLUSION: Present findings indicate that in patients who are affected by ataxia
      with oculomotor apraxia type 2, performance on neuropsychological tests,
      especially those that require rapid performance and eye or hand-eye control, must
      be analyzed with respect to oculomotor components.

PMID- 22480403
TI  - A strange face in the mirror. Face-selective self-misidentification in a patient
      with right lateralized occipito-temporal hypo-metabolism.

PMID- 22480404
TI  - I am blind, but I "see" fear.
AB  - The ability to process unseen emotional signals might offer an evolutionary
      advantage in enabling threat-detection. In the present study, patients with
      visual field defects, without any subjective awareness of stimuli presented in
      the blind field and performing at the chance level in two alternative
      discrimination tasks (Experiment 1), were tested with go-no go tasks where they
      were asked to discriminate the emotional valence (Experiment 2) or the gender
      (Experiment 3) of faces displayed in the intact field, during the concurrent
      presentation of emotional faces in the blind field. The results showed a
      facilitative effect when fearful faces were presented in the blind field, both
      when the emotional content of the stimuli was relevant (Experiment 2) and
      irrelevant (Experiment 3) to the task. These findings are in contrast with
      performances of healthy subjects and patients tested in classical blindsight
      investigations, who showed response facilitation for congruent pairs of emotional
      stimuli. The observed implicit visual processing for unseen fearful stimuli might
      represent an adaptive mechanism for the implementation of efficient defensive
      responses, probably mediated by a spared sub-cortical and short-latency pathway.

PMID- 22480405
TI  - A disruption of colour priming following continuous theta burst transcranial
      magnetic stimulation.

PMID- 22480406
TI  - Report of toxic shock syndrome toxin 1 (TSST-1) from Staphylococcus aureus
      isolated in food handlers and surfaces from foodservice establishments.
AB  - A set of 53 Staphylococcus aureus isolates collected from food handlers and
      foodservice establishments in Spain was analyzed for toxic shock syndrome toxin
      (TSST-1) production. S. aureus strains were isolated from 908 samples collected
      from different surfaces such as dish towels, workers' hands, cutting boards,
      stainless steel tables and slicers, but they were not detected neither in clean
      plates nor in kitchen knives. Only one food worker hand has been reported to be
      contaminated by TSST-1 in a restaurant. Despite this, proper hygiene practices
      should be respected for the surfaces of contact with food, as well as for the
      hands of the manipulators This is the first article, in Spain, that reports the
      detection of TSST-1 in a restaurant worker hand.

PMID- 22480407
TI  - Modelling transmission dynamics of paratuberculosis of red deer under pastoral
      farming conditions.
AB  - This study aimed to develop a mathematical model describing the dynamics of
      paratuberculosis (PTB) in red deer (Cervus elaphus) under pastoral farming
      conditions in New Zealand. The model examined infectivity differences between
      ovine and bovine strains of Mycobacterium avium subspecies paratuberculosis (MAP)
      and seasonality of MAP survival. We also evaluate variable use of pasture and the
      effect of management interventions on the infection prevalence and annual
      clinical incidence of PTB. A state-transition model was developed and calibrated
      to observed data on both prevalence of infection and incidence of clinical PTB.
      To accommodate specific PTB features for deer, the model included a fast and a
      slow track for progression of infection to disease. MAP on pasture was the source
      for horizontal transmission and infected dams for vertical transmission. In the
      presence of a single strain, an infectivity reduction of up to 80% allowed MAP to
      persist in the herd (R(0)>1). For mixed infection by two strains however, a 30%
      reduction in infectivity of one strain was sufficient to outcompete a strain with
      lower infectivity, suggesting that mixed infection of MAP strains with different
      infectivity may not be common in deer. The model showed that seasonal variation
      of MAP survival on pasture had little impact on transmission dynamics, and that
      rotational grazing with pasture spelling vs. permanent grazing of the same
      paddock reduced both infection prevalence and clinical PTB by about 50%. Based on
      model outputs, early detection of young deer in a high-shedding state was the
      most effective means of controlling PTB among the tested scenarios.

PMID- 22480408
TI  - Disease-specific patient reported outcome tools for systemic lupus erythematosus.
AB  - PURPOSE: Systemic lupus erythematosus (SLE) can significantly affect both health
      and non-health-related quality of life (HRQOL and non-HRQOL). However, of the
      existent published patient-reported outcome (PRO) tools, none were developed from
      US patients, an ethnically diverse population. Furthermore, these tools do not
      address men with SLE or assess non-HRQOL issues. Herein, we present the
      development and validation of the Lupus Patient-Reported Outcome tool (LupusPRO)
      and discuss its clinical utility and research value compared with other PRO tools
      currently available for SLE. METHODS: Beginning with a conceptual framework,
      items for LupusPRO were generated using feedback from women and men with SLE. The
      tool underwent iterations based on patient feedback and clinimetric and
      psychometric analyses. Validity (content, construct, and criterion) and
      reliability (internal consistency and test-retest) for the 44-item LupusPRO tool
      are presented. RESULTS: Consistent with the conceptual framework, items were
      identified that were related to HRQOL and non-HRQOL constructs. HRQOL domains
      included (1) lupus symptoms; (2) physical health (physical function, role
      physical); (3) pain-vitality; (4) emotional health (emotional function and role
      emotional); (5) body image; (6) cognition; (7) procreation; and (8) lupus
      medications. Non-HRQOL domains were (1) available social support and coping; (2)
      desires-goals; and (3) satisfaction with medical care. Internal consistency
      reliability (0.68-0.94), test-retest reliability (0.55-0.92), content, construct
      (r > 0.50 with SF-36), and criterion (r > -0.35 with disease activity) validity
      were fair to good. CONCLUSIONS: LupusPRO is a valid and reliable disease-targeted
      patient-reported health outcome tool that is generalizable to SLE patients in the
      United States of varied ethnic backgrounds and either gender.

PMID- 22480410
TI  - [Mild acute pancreatitis associated with cocaine consumption].

PMID- 22480411
TI  - The effect of chemotherapy or radiotherapy on thymidine phosphorylase and
      dihydropyrimidine dehydrogenase expression in cancer of the uterine cervix.
AB  - OBJECTIVE: Levels of 5-FU metabolic or related enzymes, particularly thymidine
      phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), have been
      investigated in various cancer types, including uterine cervical cancer.
      Intratumoral TP levels have been reported to increase in response to several
      chemotherapeutic agents or irradiation in both xenografts and clinical studies.
      In cervical cancer, however, only a few studies about changes in TP and DPD
      expression associated with cancer treatment have been published. We evaluated the
      effect of chemotherapy and/or irradiation on TP and DPD expression in cervical
      squamous cell carcinoma. STUDY DESIGN: Of 27 patients in this study, 12 patients
      underwent neoadjuvant chemotherapy consisting of nedaplatin, ifosfamide, and/or
      peplomycin followed by radical surgery, and 15 patients underwent radiotherapy
      (n=8) or chemoradiotherapy with nedaplatin (n=7) as initial treatment. Tumor
      specimens were obtained from biopsies acquired before treatment and after
      administration of chemotherapy (2 weeks after the first and second cycles), and
      after irradiation with 10 Gy, 20 Gy, and 30 Gy. These specimens were used to
      measure TP and DPD levels by ELISA. RESULTS: In the 12 patients who received
      neoadjuvant chemotherapy, intratumoral TP and DPD levels did not change. In
      contrast, in the 15 patients who underwent radiotherapy or chemoradiotherapy with
      nedaplatin, TP or DPD expression appeared to be slightly increased or decreased,
      respectively, after irradiation with 20 Gy, and consequently the TP/DPD ratio was
      significantly higher after irradiation with 20 Gy than before irradiation.
      CONCLUSIONS: These results suggest a clinical advantage of chemoradiotherapy with
      capecitabine or doxyfluridine over radiotherapy alone via the elevation of the
      TP/DPD ratio in cervical squamous cell carcinoma. However, no advantage of
      combination chemotherapy with these 5-FU derivatives was demonstrated. Therefore,
      further evaluation with a larger number of patients or with other
      chemotherapeutic agents is required to confirm these observations.

PMID- 22480412
TI  - Validation, cultural adaptation and responsiveness of two pelvic-floor-specific
      quality-of-life questionnaires, PFDI-20 and PFIQ-7, in a Turkish population.
AB  - OBJECTIVES: The aim of the study was cultural adaptation, validation, and test
      for responsiveness of the short forms of the Pelvic Floor Distress Inventory
      (PFDI-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7) in a Turkish
      population. STUDY DESIGN: To evaluate their validity, questionnaires were applied
      to 248 women. The questionnaires were compared with prolapse stage according to
      the Pelvic Organ Prolapse Quantification (POP-Q) system. The responsiveness of
      the questionnaires was assessed in 103 women with prolapse who also completed the
      questionnaires after reconstructive surgical treatment, with standardized
      response mean (SRM), effect size (ES), and the Wilcoxon signed-rank test.
      RESULTS: Cronbach alpha coefficients of the Turkish PFDI-20 and PFIQ-7
      questionnaires were 0.908 and 0.830, respectively. Significant correlations were
      observed between the scores of the questionnaires with the vaginal examination
      findings. The PFDI-20 and PFIQ-7 scores were significantly improved after vaginal
      reconstructive surgery. CONCLUSIONS: Turkish translated versions of the PFDI-20
      and PFIQ-7 are reliable, valid and responsive instruments for assessing symptom
      severity, impact on QoL in women with pelvic organ prolapse. They can be easily
      administered and self-completed by Turkish women.

PMID- 22480413
TI  - Best predictors of survival outcome after tertiary cytoreduction in patients with
      recurrent platinum-sensitive epithelial ovarian cancer.
AB  - OBJECTIVE: To evaluate the efficacy of tertiary cytoreduction (TCR) on survival
      and to determine prognostic factors which may influence surgical and survival
      outcome. STUDY DESIGN: Twenty-three consecutive patients who had recurrent
      platinum-sensitive epithelial ovarian cancer and underwent TCR between January
      1999 and January 2011 were evaluated. Factors which impact on TCR outcome and
      survival were determined by statistical analysis. RESULTS: TCR was optimal (< 1cm
      residual tumor) in 15 of the 23 patients (65.2%) and suboptimal in 8 patients
      (34.8%). None of the clinicopathologic factors was associated with TCR outcome.
      On the contrary, TCR outcome (optimal vs suboptimal) was independently associated
      with survival in univariate analysis (P=0.018). CONCLUSION: There is not a good
      predictor of TCR outcome but TCR seems to be beneficial for patients in whom
      optimal surgery can be achieved. Therefore, preoperative assessment of patients
      and weighing the potential survival benefit against potential surgical risks are
      very important for patient selection.

PMID- 22480414
TI  - Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF
      in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV.
AB  - OBJECTIVE: Different patterns of invasion (PIs) have prognostic impact in several
      types of cancer and are associated with different grades of peritumoral stromal
      remodeling, characterized by the desmoplastic stromal response (DSR). One key
      regulator influencing cellular motility and peritumoral stromal response is c
      met/HGF. This study evaluates the association between different PI, peritumoral
      DSR and its correlation to the expression of c-met/HGF in squamous cell
      carcinomas of the uterine cervix (CX). STUDY DESIGN: 131 advanced stage CX (FIGO
      III/IV) were re-evaluated histologically regarding PI, using a two-level scoring
      system. The tumor grows in solid cords/trabeculae in finger-like PI and in very
      small groups or single cells in spray-like PI. DSR was categorized as none/weak
      and moderate/strong. The tumors were stained with antibodies against c-met and
      HGF. The staining of >30% of tumor cells was defined as overexpression. The PI
      was correlated to the prognostic outcome, different categories of DSR and
      expression status of c-met and HGF. RESULTS: 66.4% of the tumors showed a finger
      like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year
      overall survival when compared to the finger-like PI (14.0% vs. 29.1%,
      respectively; p=0.012), and was associated with moderate/strong DSR. The majority
      of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was
      no correlation between the expression status of c-met/HGF and the FIGO stage,
      peritumoral DSR or the prognostic outcome. CONCLUSIONS: Spray-like PI is of
      prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong
      peritumoral stromal remodeling. There is no prognostic impact of the
      immunohistochemical expression of c-met/HGF in advanced stage cervical
      carcinomas.

PMID- 22480415
TI  - Misdiagnosis of rodenticide poisoning as ectopic pregnancy: a case report.

PMID- 22480416
TI  - Isolation and phenotypic characterisation of stem cells from late stage
      osteoarthritic mesenchymal tissues.
AB  - INTRODUCTION: Osteoarthritis (OA) represents an increasing health issue
      worldwide. Regenerative medicine (RM) has raised the hope for introducing
      revolutionary therapies in clinical practice. Detection of autologus cell sources
      can improve accessibility to RM strategies. OBJECTIVES: To assess the presence
      and biological potential of mesehchymal stem cells in three tissues (subchondral
      bone, synovial layer, periarticular adipose tissue) in late stages osteoarthritic
      patients. MATERIAL AND METHODS: Samples were collected from subjects undergoing
      total knee replacement (TKR). MSCs were isolated and cultured in complete
      alphaMEM with beta FGF. Cell morphology and growth potential was assessed. Flow
      cytometry was used for detection of several relevant cell surface markers.
      Quantitative and qualitative assessment of differentiation potential towards
      three mesenchymal lineages (osteogenesis adipogenesis chondrogenesis) was
      performed. Time lapse life cell imaging of nondiferentiated cells over 24 hours
      period was used to determine cell kinetics. RESULTS: Mesenchymal cells derived
      from all donors and tissue types showed morphology, growth and surface cell
      markers associated with stemness. All cell types underwent differentiation toward
      three mesenchymal lineages with significant differences between tissues of
      origin, not between donors. Cell kinetics, as derived from life imaging records,
      was variable with tissue of origin, significant higher for adipose derived MSCS.
      CONCLUSION: Human late stage OA mesenchymal tissues, contain progenitors with
      proliferative and differentiation potential of MSCs. These populations can be
      used for research and autologus regenerative therapies. Further comparative
      studies with age matched non OA samples has the potential of contributing to
      deepening knowledge about disease occurrence and progression.

PMID- 22480417
TI  - Non invasive cardiac vein mapping: role of multislice CT coronary angiography.
AB  - PURPOSE: Coronary venous anatomy is of primary importance when implanting a
      cardiac resynchronization therapy device, besides, the coronary sinus can be
      differently enlarged depending on chronic heart failure. The aim of this study is
      to evaluate the usefulness of Coronary CTA in describing the coronary venous tree
      and in particular the coronary sinus and detecting main venous system variants.
      MATERIALS AND METHODS: 301 consecutive patients (196 ?, mean age 63.74 years)
      studied for coronary artery disease with 64 slice Coronary CTA were
      retrospectively examined. The acquisition protocol was the standard acquisition
      one used for coronary artery evaluation but the cardiac venous system were
      visualized. The cardiac venous system was depicted using 3D, MPR, cMPR and MIP
      post-processing reconstructions on an off-line workstation. For each patient
      image quality, presence and caliber of the coronary sinus (CS), great cardiac
      vein (GCV), middle vein (MV), anterior interventricular vein (AIV), lateral
      cardiac vein (LCV), posterior cardiac vein (PCV), small cardiac vein (SCV) and
      presence of variant of the normal anatomy were examined and recorded. RESULTS:
      CS, GCV, MV and AIV were visualized in 100% of the cases. The LCV was visualized
      in 255/301 (84%) patients, the PCV in 248/301 (83%) patients and the SCV in
      69/301 (23%) patients. Mean diameter of the CS was 8.7 mm in 276/301 (91.7%)
      patients without chronic heart failure and 9.93 mm in 25/301 (8.3%) patients with
      chronic heart failure. CONCLUSIONS: Coronary CTA allows non invasive mapping of
      the cardiac venous system and may represent a useful presurgical tool for
      biventricular pacemaker devices implantation.

PMID- 22480418
TI  - Long-term activation of semicarbazide-sensitive amine oxidase lowers circulating
      levels of uric acid in diabetic conditions.
AB  - Uric acid is involved in nitrogenous waste in animals, together with ammonia and
      urea. Uric acid has also antioxidant properties and is a surrogate marker of
      metabolic syndrome. We observed that the elevated plasma uric acid of high-fat
      fed mice was normalized by benzylamine treatment. Indeed, benzylamine is the
      reference substrate of semicarbazide-sensitive amine oxidase (SSAO), an enzyme
      highly expressed in fat depots and vessels, which generates ammonia when
      catalysing oxidative deamination. Ammonia interferes with uric acid
      metabolism/solubility. Our aim was therefore to investigate whether the lowering
      action of benzylamine on uric acid was related to an improvement of diabetic
      complications, or was connected with SSAO-dependent ammonia production. First, we
      observed that benzylamine administration lowered plasma uric acid in diabetic
      db/db mice while it did not modify uric acid levels in normoglycemic and lean
      mice. In parallel, benzylamine improved the glycemic control in diabetic but not
      in normoglycemic mice, while plasma urea remained unaltered. Then, uric acid
      plasma levels were measured in mice invalidated for AOC3 gene, encoding for SSAO.
      These mice were unable to oxidize benzylamine but were not diabetic and exhibited
      unaltered plasma uric levels. Therefore, activated or abolished ammonia
      production by SSAO was without influence on uric acid in the context of
      normoglycemia. Our observations confirm that plasma uric acid increases with
      diabetes and can be normalized when glucose tolerance is improved. They also show
      that uric acid, a multifunctional metabolite at the crossroads of nitrogen waste
      and of antioxidant defences, can be influenced by SSAO, in a manner apparently
      related to changes in glucose homeostasis.

PMID- 22480419
TI  - An antagonist of GABA-B receptors potentiates activity of cortical epileptic
      foci.
AB  - Cortical epileptic foci elicited by local application of bicuculline methiodide
      represent a model of interictal epileptic activity with a transition into ictal
      phases. We studied a role of GABA-B receptors in this model using GABA-B receptor
      antagonist CGP35348 in adult rats with implanted cortical electrodes and cannula.
      CGP35348 (100 or 200 mg/kg i.p.) did not affect interictal discharges but it
      augmented ictal activity. Latency to the first ictal episode was decreased by the
      lower dose of CGP35348, duration of episodes was increased by the higher dose.
      GABA-B receptor antagonist did not influence purely cortical epileptic phenomenon
      but it is proconvulsant in ictal activity generated with participation of
      subcortical structures.

PMID- 22480420
TI  - Idebenone-induced recovery of glycerol-3-phosphate and succinate oxidation
      inhibited by digitonin.
AB  - Digitonin solubilizes mitochondrial membrane, breaks the integrity of the
      respiratory chain and releases two mobile redox-active components: coenzyme Q
      (CoQ) and cytochrome c (cyt c). In the present study we report the inhibition of
      glycerol-3-phosphate- and succinate-dependent oxygen consumption rates by
      digitonin treatment. Our results show that the inhibition of oxygen consumption
      rates is recovered by the addition of exogenous synthetic analog of CoQ idebenone
      (hydroxydecyl-ubiquinone; IDB) and cyt c. Glycerol-3-phosphate oxidation rate is
      recovered to 148 % of control values, whereas succinate-dependent oxidation rate
      only to 68 %. We find a similar effect on the activities of glycerol-3-phosphate
      and succinate cytochrome c oxidoreductase. Our results also indicate that
      succinate-dependent oxidation is less sensitive to digitonin treatment and less
      activated by IDB in comparison with glycerol-3-phosphate-dependent oxidation.
      These findings might indicate the different mechanism of the electron transfer
      from two flavoprotein-dependent dehydrogenases (glycerol-3-phosphate
      dehydrogenase and succinate dehydrogenase) localized on the outer and inner face
      of the inner mitochondrial membrane, respectively.

PMID- 22480421
TI  - Central corneal thickness considered an index of corneal hydration of the UVB
      irradiated rabbit cornea as influenced by UVB absorber.
AB  - UVB radiation from sunlight induces an acute corneal inflammation,
      photokeratitis, accompanied by changes in corneal hydration. We employed a method
      of ultrasonic pachymetry for daily examination of central corneal thickness as an
      index of corneal hydration of the rabbit cornea repeatedly irradiated by UVB
      radiation (312 nm, daily dose of 0.25 J/cm(2) during three or four days) as
      influenced by UVB absorber (actinoquinol combined with hyaluronic acid) dropped
      on the ocular surface during irradiation. One day after the third irradiation
      procedure the animals were sacrificed and corneas examined immuno-histochemically
      for peroxynitrite formation, a marker of oxidative damage, the antioxidant
      aldehyde dehydrogenase 3A1 and endothelial nitric oxide synthase, an enzyme
      generated nitric oxide. Results show that UV absorber combined with hyaluronic
      acid protected the cornea against UVB-induced changes in corneal thickness and
      microscopical disturbances to the cornea (both seen after buffered saline
      application) until the fourth experimental day. These UVB doses are equivalent to
      a daily exposure of 2.5 hrs of the human cornea to solar UVB radiation for three
      consecutive days. It is suggested that actinoquinol/ hyaluronic acid drops might
      be helpful for the human eye in the defence against photooxidative and other
      oxidative processes.

PMID- 22480422
TI  - Autophagy-lysosomal pathway is involved in lipid degradation in rat liver.
AB  - We present data supporting the hypothesis that the lysosomal-autophagy pathway is
      involved in the degradation of intracellular triacylglycerols in the liver. In
      primary hepatocytes cultivated in the absence of exogenous fatty acids (FFA),
      both inhibition of autophagy flux (asparagine) or lysosomal activity
      (chloroquine) decreased secretion of VLDL (very low density lipoproteins) and
      formation of FFA oxidative products while the stimulation of autophagy by
      rapamycine increased some of these parameters. Effect of rapamycine was
      completely abolished by inactivation of lysosomes. Similarly, when autophagic
      activity was influenced by cultivating the hepatocytes in "starving" (amino-acid
      poor medium) or "fed" (serum-supplemented medium) conditions, VLDL secretion and
      FFA oxidation mirrored the changes in autophagy being higher in starvation and
      lower in fed state. Autophagy inhibition as well as lysosomal inactivation
      depressed FFA and DAG (diacylglycerol) formation in liver slices in vitro. In
      vivo, intensity of lysosomal lipid degradation depends on the formation of
      autophagolysosomes, i.e. structures bringing the substrate for degradation and
      lysosomal enzymes into contact. We demonstrated that lysosomal lipase (LAL)
      activity in liver autophagolysosomal fraction was up-regulated in fasting and
      down-regulated in fed state together with the increased translocation of LAL and
      LAMP2 proteins from lysosomal pool to this fraction. Changes in autophagy
      intensity (LC3-II/LC3-I ratio) followed a similar pattern.

PMID- 22480424
TI  - Age-related changes in postural responses to backward platform translation.
AB  - The aim of the study was to investigate age-related changes in postural responses
      to platform translation with 3 various velocities. We focused on the influence of
      linear velocity using the smoothed profile of platform acceleration (till 100
      cm.s(-2)). Eleven healthy young (20-31 years) and eleven healthy elderly (65-76
      years) subjects were examined. The subjects stood on the force platform with
      their eyes closed. Each trial (lasting for 8 sec) with different velocity (10,
      15, 20 cm.s(-1)) of 20 cm backward platform translation was repeated 4 times. We
      have recorded displacements of the centre of pressure (CoP) and the EMG activity
      of gastrocnemius muscle (GS) and tibialis anterior muscle (TA). The results
      showed increased maximal values of CoP responses to the platform translation.
      There was also observed a scaling delay of CoP responses to platform translation
      with different velocities in elderly. The EMG activity of GS muscle during
      backward platform translation was of about similar shape in both groups during
      the slowest platform velocity, but it increased depending on rising velocity. EMG
      activity of TA was not related to the platform velocity. Early parts of postural
      responses showed significant co-activation of TA and GS muscles of elderly. It is
      likely that elderly increased body stiffening in order to help their further
      balance control.

PMID- 22480423
TI  - Dependence of spontaneous electrical activity and basal prolactin release on
      nonselective cation channels in pituitary lactotrophs.
AB  - All secretory anterior pituitary cells fire action potentials spontaneously and
      exhibit a high resting cation conductance, but the channels involved in the
      background permeability have not been identified. In cultured lactotrophs and
      immortalized GH(3) cells, replacement of extracellular Na(+) with large organic
      cations, but not blockade of voltage-gated Na(+) influx, led to an instantaneous
      hyperpolarization of cell membranes that was associated with a cessation of
      spontaneous firing. When cells were clamped at -50 mV, which was close to the
      resting membrane potential in these cells, replacement of bath Na(+) with organic
      cations resulted in an outward-like current, reflecting an inhibition of the
      inward holding membrane current and indicating loss of a background-depolarizing
      conductance. Quantitative RT-PCR analysis revealed the high expression of mRNA
      transcripts for TRPC1 and much lower expression of TRPC6 in both lactotrophs and
      GH(3) cells. Very low expression of TRPC3, TRPC4, and TRPC5 mRNA transcripts were
      also present in pituitary but not GH(3) cells. 2-APB and SKF-96365, relatively
      selective blockers of TRPC channels, inhibited electrical activity, Ca(2+) influx
      and prolactin release in a concentration-dependent manner. Gd(3+), a common
      Ca(2+) channel blocker, and flufenamic acid, an inhibitor of non-selective cation
      channels, also inhibited electrical activity, Ca(2+) influx and prolactin
      release. These results indicate that nonselective cation channels, presumably
      belonging to the TRPC family, contribute to the background depolarizing
      conductance and firing of action potentials with consequent contribution to
      Ca(2+) influx and hormone release in lactotrophs and GH(3) cells.

PMID- 22480425
TI  - Development of oxytocin- and vasopressin-network in the supraoptic and
      paraventricular nuclei of fetal sheep.
AB  - The hypothalamic supraoptic and paraventricular nuclei consist of oxytocin and
      arginine vasopressin synthesizing neurons that send projections to the
      neurohypophysis. A growing body of evidence in adult animals and young animals at
      near term confirmed the structure and function in the vasopressinergic and
      oxytocinergic network. However, whether those distinctive neural networks are
      formed before near term is largely unknown. This study determined the special
      patterns in location and distribution of oxytocin- and vasopressin-neurons in the
      paraventricular and supraoptic nuclei from preterm to term in the ovine fetuses.
      The results showed that oxytocin- and vasopressin-neurons were present in both
      nuclei at the three gestational time periods (preterm, near term, and term). In
      the paraventricular nuclei, vasopressin-cells concentrated mainly in the core of
      the middle magnocellular paraventricular nuclei, and oxytocin-cells were
      scattered surrounding the core. In the supraoptic nuclei, vasopressin-cells
      mostly located in the ventral part, and oxytocin-cells in the dorsal part. The
      data demonstrated that the special distributed patterns of vasopressin- and
      oxytocin-neuron network have formed in those two nuclei at least from preterm.
      Intracerebroventricular injection of angiotensin II significantly increased fetal
      plasma oxytocin and vasopressin levels at preterm, which was associated with an
      increase of oxytocin- and vasopressin-neuron activity marked with c-fos
      expression. The data provided new evidence for the structural and functional
      development of the oxytocin- and vasopressin-network before birth.

PMID- 22480426
TI  - Late divergence of target and nontarget ERPs in a visual oddball task.
AB  - Different mental operations were expected in the late phase of intracerebral ERPs
      obtained in the visual oddball task with mental counting. Therefore we searched
      for late divergences of target and nontarget ERPs followed by components
      exceeding the temporal window of the P300 wave. Electrical activity from 152
      brain regions of 14 epileptic patients was recorded by means of depth electrodes.
      Average target and nontarget records from 1800 ms long EEG periods free of
      epileptic activity were compared. Late divergence preceded by almost identical
      course of the target and nontarget ERPs was found in 16 brain regions of 6
      patients. The mean latency of the divergence point was 570+/-93 ms after the
      stimulus onset. The target post-divergence section of the ERP differed from the
      nontarget one by opposite polarity, different latency of the components, or even
      different number of the components. Generators of post-divergence ERP components
      were found in the parahippocampal gyrus, superior, middle and inferior temporal
      gyri, amygdala, and fronto-orbital cortex. Finding of late divergence indicates
      that functional differences exist even not sooner than during the final phase of
      the task.

PMID- 22480427
TI  - Atropa belladonna L. water extract: modulator of extracellular matrix formation
      in vitro and in vivo.
AB  - Previously, we found that treatment of cutaneous wounds with Atropa belladonna L.
      (AB) revealed shortened process of acute inflammation as well as increased
      tensile strength and collagen deposition in healing skin wounds (Gal et al.
      2009). To better understand AB effect on skin wound healing male Sprague-Dawley
      rats were submitted to one round full thickness skin wound on the back. In two
      experimental groups two different concentrations of AB extract were daily applied
      whereas the control group remained untreated. For histological evaluation samples
      were removed on day 21 after surgery and stained for wide spectrum cytokeratin,
      collagen III, fibronectin, galectin-1, and vimentin. In addition, in the in vitro
      study different concentration of AB extract were used to evaluate differences in
      HaCaT keratinocytes proliferation and differentiation by detection of Ki67 and
      keratin-19 expressions. Furthermore, to assess ECM formation of human dermal
      fibroblasts on the in vitro level fibronectin and galectin-1 were visualized. Our
      study showed that AB induces fibronectin and galectin-1 rich ECM formation in
      vitro and in vivo. In addition, the proliferation of keratinocytes was also
      increased. In conclusion, AB is an effective modulator of skin wound healing.
      Nevertheless, further research is needed to find optimal therapeutic
      concentration and exact underlying mechanism of action.

PMID- 22480428
TI  - T2D risk haplotypes of the TCF7L2 gene in the Czech population sample: the
      association with free fatty acids composition.
AB  - The association of transcription factor 7-like 2 (TCF7L2) gene variants with the
      pathogenesis of T2D, gestational diabetes and polycystic ovary syndrome (PCOS)
      was examined. The study involved 1460 individuals: 347 T2D patients (D); 261
      gestational diabetics (G); 147 offspring of T2D (O); 329 women with PCOS, and 376
      controls (C). The SNPs: rs7901695; rs7903146; rs12255372 in the TCF7L2 gene were
      genotyped. Anthropometric and biochemical parameters, oGTT derived indices were
      assessed. In addition, free fatty acids (FFAs) were evaluated in 183 non-diabetic
      women. The CTT haplotype showed the strongest association with T2D with OR 1.57,
      p=0.0003. The frequency of the CTT/CTT haplotype was decreasing in following
      order: D 10.6, O 9.5, G 6.1, C 5.3 and PCOS 4.9 [%]. Among CTT carriers,
      significantly decreased levels of oGTT-stimulated insulin and C-peptide as well
      as proportions of fasting PUFAs were observed. The carriership of CTG/TCG was
      associated with gestational diabetes, OR 2.59, p=0.036. The association of TCF7L2
      haplotypes with T2D and gestational diabetes but not with PCOS was confirmed.
      Novel association of TCF7L2 with FFAs composition was found.

PMID- 22480429
TI  - Ancient whole genome duplications, novelty and diversification: the WGD Radiation
      Lag-Time Model.
AB  - Many large and economically important plant groups (e.g. Brassicaceae, Poaceae,
      Asteraceae, Fabaceae and Solanaceae) have had ancient whole genome duplications
      (WGDs) occurring near or at the time of their origins, suggesting that WGD
      contributed to the origin of novel key traits and drove species diversification.
      However, these large clades show phylogenetic asymmetries with a species-rich
      crown group and a species-poor sister clade, suggesting significant 'lag-times'
      between WGDs and radiations. The species-poor sister groups share many key
      traits, but are often restricted to the hypothesized center of origin for the
      larger clade. Thus, the ultimate success of the crown group does not only involve
      the WGD and novel key traits, but largely subsequent evolutionary phenomena
      including later migration events, changing environmental conditions and/or
      differential extinction rates.

PMID- 22480430
TI  - Rarely successful polyploids and their legacy in plant genomes.
AB  - Polyploidy, or whole genome duplication, is recognized as an important feature of
      eukaryotic genome evolution. Among eukaryotes, polyploidy has probably had the
      largest evolutionary impact on vascular plants where many contemporary species
      are of recent polyploid origin. Genomic analyses have uncovered evidence of at
      least one round of polyploidy in the ancestry of most plants, fueling speculation
      that genome duplications lead to increases in net diversity. In spite of the
      frequency of ancient polyploidy, recent analyses have found that recently formed
      polyploid species have higher extinction rates than their diploid relatives.
      These results suggest that despite leaving a substantial legacy in plant genomes,
      only rare polyploids survive over the long term and most are evolutionary dead
      ends.

PMID- 22480431
TI  - Integration of local and systemic signaling pathways for plant N responses.
AB  - Nitrogen (N) is an essential macronutrient and a signal that has profound impacts
      on plant growth and development. In order to cope with changing N regimes in the
      soil, plants have developed complex regulatory mechanisms that involve short
      range and long-range signaling pathways. These pathways act at the cellular and
      whole plant scale to coordinate plant N metabolism, growth and development
      according to external and internal N status. Although molecular components of
      local and systemic N signaling have been identified and characterized, an
      integrated view of how plants coordinate and organize the N response is still
      lacking. In this review, we discuss recent advances toward understanding the
      mechanisms of local and systemic N responses and provide an integrated model for
      how these responses are orchestrated.

PMID- 22480432
TI  - The facile synthesis of multifunctional PAMAM dendrimer conjugates through copper
      free click chemistry.
AB  - The facile conjugation of three azido modified functionalities, namely a
      therapeutic drug (methotrexate), a targeting moiety (folic acid), and an imaging
      agent (fluorescein) with a G5 PAMAM dendrimer scaffold with cyclooctyne molecules
      at the surface through copper-free click chemistry is reported. Mono-, di-, and
      tri-functional PAMAM dendrimer conjugates can be obtained via combinatorial
      mixing of different azido modified functionalities simultaneously or sequentially
      with the dendrimer platform. Preliminary flow cytometry results indicate that the
      folic acid targeted nanoparticles are efficiently binding with KB cells.

PMID- 22480433
TI  - An Hsp90 modulator that exhibits a unique mechanistic profile.
AB  - Described is the synthesis of two biotinylated derivatives of a cytotoxic
      macrocycle. Pull-down assays indicate that this macrocycle targets the N-middle
      domain of Hsp90. Untagged compound can effectively compete away tagged compound
      Hsp90 protein complexes, confirming the binding specificity of the macrocycle for
      Hsp90. The macrocycle is similar in potency to other structurally-related analogs
      of Sansalvamide A (San A) and induces apoptosis via a caspase 3 mechanism. Unlike
      other San A derivatives, we show that the macrocycle does not inhibit binding
      between C-terminal client proteins and co-chaperones and Hsp90, suggesting that
      it has a unique mechanism of action.

PMID- 22480434
TI  - Estimating the incidence of an epidemic when it is first discovered and the
      design of early detection monitoring.
AB  - The early detection of an invading epidemic is crucial for successful disease
      control. Although models have been used extensively to test control strategies
      following the first detection of an epidemic, few studies have addressed the
      issue of how to achieve early detection in the first place. Moreover, sampling
      theory has made great progress in understanding how to estimate the incidence or
      spatial distribution of an epidemic but how to sample for early detection has
      been largely ignored. Using a simple epidemic model we demonstrate a method to
      calculate the incidence of an epidemic when it is discovered for the first time
      (given a monitoring programme taking samples at regular intervals). We use the
      method to explore how the intensity and frequency of sampling influences early
      detection. In particular, we find that for epidemics characterised by high
      population growth rates it is most effective to spread sampling resources evenly
      in time. In addition we derive a useful approximation to our method which results
      in a simple equation capturing the relation between monitoring and epidemic
      dynamics. Not only does this provide valuable new insight but it provides a
      simple rule of thumb for the design of monitoring programmes in practice.

PMID- 22480435
TI  - Infection of HIV-specific CD4 T helper cells and the clonal composition of the
      response.
AB  - A hallmark of human immunodeficiency virus is its ability to infect CD4+ T helper
      cells, thus impairing helper cell responses and consequently effector responses
      whose maintenance depends on help (such as killer T cells and B cells). In
      particular, the virus has been shown to infect HIV-specific helper cells
      preferentially. Using mathematical models, we investigate the consequence of this
      assumption for the basic dynamics between HIV and its target cells, assuming the
      existence of two independently regulated helper cell clones, directed against
      different epitopes of the virus. In contrast to previous studies, we examine a
      relatively simple scenario, only concentrating on the interactions between the
      virus and its target cells, not taking into account any helper-dependent effector
      responses. Further, there is no direct competition for space or antigenic
      stimulation in the model. Yet, a set of interesting outcomes is observed that
      provide further insights into factors that shape helper cell responses. Despite
      the absence of competition, a stronger helper cell clone can still exclude a
      weaker one because the two clones are infected by the same pathogen, an
      ecological concept called "apparent competition". Moreover, we also observe
      "facilitation": if one of the helper cell clones is too weak to become
      established in isolation, the presence of a stronger clone can provide enhanced
      antigenic stimulation, thus allowing the weaker clone to persist. The
      dependencies of these outcomes on parameters is explored. Factors that reduce
      viral infectivity and increase the death rate of infected cells promote
      coexistence, which is in agreement with the observation that stronger immunity
      correlates with broader helper cell responses. The basic model is extended to
      explicitly take into account helper-dependent CTL responses and direct
      competition. This study sheds further light onto the factors that can influence
      the clonal composition of HIV-specific helper cell responses, which has
      implications for the overall pattern of disease progression.

PMID- 22480436
TI  - Abdominal inflammatory myofibroblastic tumour.

PMID- 22480437
TI  - Pilates based core stability training in ambulant individuals with multiple
      sclerosis: protocol for a multi-centre randomised controlled trial.
AB  - BACKGROUND: People with Multiple Sclerosis (MS) frequently experience balance and
      mobility impairments, including reduced trunk stability. Pilates-based core
      stability training, which is aimed at improving control of the body's stabilising
      muscles, is popular as a form of exercise with people with MS and therapists. A
      replicated single case series study facilitated by the Therapists in MS Group in
      the United Kingdom (UK) provides preliminary evidence that this approach can
      improve balance and mobility in ambulant people with MS; further evidence is
      needed to substantiate these findings to ensure that limited time, energy,
      finances and resources are used to best effect.This study builds upon the pilot
      work undertaken in the case series study by implementing a powered randomised
      controlled study, with the aims of: 1 Establishing the effectiveness of core
      stability training; 2 Comparing core stability training with standardised
      physiotherapy exercise; 3 Exploring underlying mechanisms of change associated
      with this intervention METHODS: This is a multi-centre, double blind, block
      randomised, controlled trial. Eligible participants will be recruited from 4 UK
      centres. Participants will be randomly allocated to one of three groups: Pilates
      based core stability training, standardised physiotherapy exercise or contract
      relax relaxation sessions (placebo control). All will receive face to face
      training sessions over a 12 week period; together with a 15 minute daily home
      programme. All will be assessed by a blinded assessor before training, at the end
      of the 12 week programme and at 4 week follow-up. The primary outcome measure is
      the 10 metre timed walk. Secondary outcome measures are the MS walking Scale
      (MSWS-12), the Functional Reach (forwards and lateral), a 10 point Numerical
      Rating Scale to determine "Difficulty in carrying a drink when walking", and the
      Activities-specific Balance Confidence (ABC) Scale. In addition, ultrasound
      imaging of the abdominal muscles will be performed before and after intervention
      to assess changes in abdominal musculature at one of the four centres (Plymouth).
      DISCUSSION: This pragmatic trial will assess the effect of these exercise
      programmes on ambulatory people with MS. It may not be possible to extrapolate
      the conclusions to those who are non-ambulatory. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01414725.

PMID- 22480438
TI  - Resolution of volatile fuel compound profiles from Ascocoryne sarcoides: a
      comparison by proton transfer reaction-mass spectrometry and solid phase
      microextraction gas chromatography-mass spectrometry.
AB  - Volatile hydrocarbon production by Ascocoryne sacroides was studied over its
      growth cycle. Gas-phase compounds were measured continuously with a proton
      transfer reaction-mass spectrometry (PTR-MS) and at distinct time points with gas
      chromatography-mass spectrometry (GC-MS) using head space solid phase
      microextraction (SPME). The PTR-MS ion signal permitted temporal resolution of
      the volatile production while the SPME results revealed distinct compound
      identities. The quantitative PTR-MS results showed the volatile production was
      dominated by ethanol and acetaldehyde, while the concentration of the remainder
      of volatiles consistently reached 2,000 ppbv. The measurement of alcohols from
      the fungal culture by the two techniques correlated well. Notable compounds of
      fuel interest included nonanal, 1-octen-3-ol, 1-butanol, 3-methyl- and
      benzaldehyde. Abiotic comparison of the two techniques demonstrated SPME fiber
      bias toward higher molecular weight compounds, making quantitative efforts with
      SPME impractical. Together, PTR-MS and SPME GC-MS were shown as valuable tools
      for characterizing volatile fuel compound production from microbiological
      sources.

PMID- 22480439
TI  - Tyrosine kinase signaling and the emergence of multicellularity.
AB  - Tyrosine phosphorylation is an essential element of signal transduction in
      multicellular animals. Although tyrosine kinases were originally regarded as
      specific to the metazoan lineage, it is now clear that they evolved prior to the
      split between unicellular and multicellular eukaryotes (~600million years ago).
      Genome analyses of choanoflagellates and other protists show an abundance of
      tyrosine kinases that rivals the most complex animals. Some of these kinases are
      orthologs of metazoan enzymes (e.g., Src), but others display unique domain
      compositions not seen in any metazoan. Biochemical experiments have highlighted
      similarities and differences between the unicellular and multicellular tyrosine
      kinases. In particular, it appears that the complex systems of kinase
      autoregulation may have evolved later in the metazoan lineage.

PMID- 22480440
TI  - The PDZ-binding motif of MCC is phosphorylated at position -1 and controls
      lamellipodia formation in colon epithelial cells.
AB  - In this study, we describe a new post-translational modification at position -1
      of the PDZ-binding motif in the mutated in colorectal cancer (MCC) protein and
      its role in lamellipodia formation. Serine 828 at position -1 of this motif is
      phosphorylated, which is predicted to increase MCC binding affinity with the
      polarity protein Scrib. We show that endogenous MCC localizes at the active
      migratory edge of cells, where it interacts with Scrib and the non-muscle motor
      protein Myosin-IIB. Expression of MCC harboring a phosphomimetic mutation MCC
      S828D strongly impaired lamellipodia formation and resulted in accumulation of
      Myosin-IIB in the membrane cortex fraction. We propose that MCC regulates
      lamellipodia formation by binding to Scrib and its downstream partner Myosin-IIB
      in a multiprotein complex. Importantly, we propose that the function of this
      complex is under the regulation of a newly described phosphorylation of the PDZ
      binding motif at position -1.

PMID- 22480441
TI  - Influence of estrogen levels on thermal perception, pain thresholds, and pain
      tolerance: studies on women undergoing in vitro fertilization.
AB  - We examined the relationship between estrogen and pain in women undergoing in
      vitro fertilization (IVF). Quantitative sensory tests (QST) were performed twice
      during the IVF-regimen: once during hormonal down-regulation and once during
      hormonal up-regulation. A group of healthy men and a group of women using
      monophasic contraceptives were also examined, to control for session-to-session
      effects. Among the women undergoing IVF, serum 17beta-estradiol levels differed
      strongly between treatments as expected, and increased from 65.7 (SD = 26) pmol/L
      during the down-regulation phase, to 5,188 (SD = 2,524) pmol/L during the up
      regulation phase. Significant outcomes in the QST were only seen for temperature
      perception thresholds (1.7  degrees C versus 2.2  degrees C; P = .003) and cold
      pain threshold (11.5  degrees C versus 14.5  degrees C; P = .04). A similar
      change in cold pain threshold was also seen in the 2 control groups, however, and
      statistical analysis suggested that this change was due to a session-to-session
      effect rather than being the result of hormonal modulation. Heat pain thresholds,
      heat tolerance, pressure pain thresholds, and the cold pressor test showed no
      significant differences between sessions. These data demonstrate that pain
      perception and pain thresholds in healthy women show little, if any, changes even
      with major variations in serum estradiol levels. PERSPECTIVE: This study shows
      that pain perception and tolerance in women undergoing in vitro fertilization do
      not vary, despite the dramatic changes in 17beta-estradiol levels induced by the
      treatment regimen. The result thus suggests that in humans, contrary to
      experimental animals, changes in estrogen levels have little influence on pain
      sensitivity.

PMID- 22480444
TI  - Degradation and healing mechanisms of carbon fibers during the catalytic growth
      of carbon nanotubes on their surfaces.
AB  - This study reports on the main cause of the reduced tensile strength of carbon
      fibers (CFs) by investigating the microstructural changes in the CFs that are
      undergoing mainly two processes: catalyst nanoparticle formation and chemical
      vapor deposition (CVD). Interestingly, the two processes oppositely influenced
      the tensile strength of the CFs: the former negatively and the latter positively.
      The catalysts coating and nanoparticle formation degraded the CF surface by
      inducing amorphous carbons and severing graphitic layers, while those defects
      were healed by both the injected carbons and interfaced CNTs during the CVD
      process. The revealed degradation and healing mechanisms can serve as a
      fundamental engineering basis for exploring optimized processes in the
      manufacturing of hierarchical reinforcements without sacrificing the tensile
      strength of the substrate CFs.

PMID- 22480442
TI  - Effectiveness of switching from long-acting injectable fluphenazine or
      haloperidol decanoate to long-acting injectable risperidone microspheres: an open
      label, randomized controlled trial.
AB  - OBJECTIVE: This multisite randomized trial addressed risks and benefits of
      staying on long-acting injectable haloperidol or fluphenazine versus switching to
      long-acting injectable risperidone microspheres. METHOD: From December 2004
      through March 2008, adult outpatients with a Structured Clinical Interview for
      DSM-IV Axis I Disorders-Patient Edition diagnosis of schizophrenia or
      schizoaffective disorder who were taking haloperidol decanoate (n = 40) or
      fluphenazine decanoate (n = 22) were randomly assigned to stay on current long
      acting injectable medication or switch to risperidone microspheres and followed
      for 6 months under study protocol and an additional 6 months naturalistic follow
      up. Kaplan-Meier and Cox regression analyses were used to examine the primary
      outcome (time to treatment discontinuation), and random regression models were
      used to examine secondary outcomes. RESULTS: Groups did not differ significantly
      in time to treatment discontinuation through 6 months of protocol-driven
      treatment. When the 6-month naturalistic follow-up period was included, time to
      treatment discontinuation was significantly shorter for individuals assigned to
      switch than for individuals assigned to stay (10% of stayers discontinued versus
      31% of switchers; P = .01). Groups did not differ with respect to
      psychopathology, hospitalizations, sexual side effects, new-onset tardive
      dyskinesia, or new-onset extrapyramidal symptoms. However, those randomized to
      switch to long-acting injectable risperidone microspheres had greater increases
      in body mass (increase of 1.0 body mass index [BMI] versus decrease of -0.3 BMI;
      P = .00) and prolactin (maximum increase to 23.4 ng/mL versus decrease to 15.2
      ng/mL, P = .01) compared to those randomized to stay. CONCLUSION: Switching from
      haloperidol decanoate or fluphenazine decanoate to risperidone microspheres
      resulted in more frequent treatment discontinuation as well as significant weight
      gain and increases in prolactin. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00044655.

PMID- 22480445
TI  - Neurogeometry of color vision.
AB  - In neurogeometry, principles of differential geometry and neuron dynamics are
      used to model the representation of forms in the primary visual cortex, V1. This
      approach is well-suited for explaining the perception of illusory contours such
      as Kanizsa's figure (see Petitot (2008) for a review). In its current version,
      neurogeometry uses achromatic inputs to the visual system as the starting-point
      for form estimation. Here we ask how neurogeometry operates when the input is
      chromatic as in color vision. We propose that even when considering only the
      perception of form, the random nature of the cone mosaic must be taken into
      account. The main challenge for neurogeometry is to explain how achromatic
      information could be estimated from the sparse chromatic sampling provided by the
      cone mosaic. This article also discusses the non-linearity involved in a neural
      geometry for chromatic processing. We present empirical results on color
      discrimination to illustrate the geometric complexity for the discrimination
      contour when the adaptation state of the observer is not conditioned. The
      underlying non-linear geometry must conciliate both mosaic sampling and
      regulation of visual information in the visual system.

PMID- 22480446
TI  - An uncertainty principle underlying the functional architecture of V1.
AB  - We present a model of the morphology of orientation maps in V1 based on the
      uncertainty principle of the SE(2) group. Starting from the symmetries of the
      cortex, suitable harmonic analysis instruments are used to obtain coherent states
      in the Fourier domain as minimizers of the uncertainty. Cortical activities
      related to orientation maps are then obtained by projection on a suitable
      cortical Fourier basis.

PMID- 22480447
TI  - Relationship between serum homocysteine levels and depressive symptoms: the
      Cooper Center Longitudinal Study.
AB  - OBJECTIVE: Elevated serum levels of the amino acid homocysteine (HCY) are
      associated with a variety of diseases. To resolve conflicting findings in studies
      that suggest a relationship between elevated serum HCY levels and depression, we
      examined the relationship between HCY levels and depressive symptoms in the
      largest sample studied to date. METHOD: We conducted a cross-sectional study of
      11,757 participants (68.9% men) aged 20 to 90 years who completed preventive
      health examinations at the Cooper Clinic, Dallas, Texas, from 2007 to 2010.
      Currently experiencing depression was defined as a 10-item Center for
      Epidemiologic Studies Depression Scale (CES-D) score of >= 10. Serum HCY levels
      were obtained. Data were analyzed in a multiple logistic regression model of CES
      D score of >= 10. RESULTS: When controlling for age, sex, body mass index,
      exercise, education, smoking, antidepressant use, creatinine level, alcohol use,
      and chronic medical conditions, elevated HCY was associated with 26% greater odds
      of currently experiencing depressive symptoms (P = .007) as defined by CES-D
      score. CONCLUSIONS: In the largest sample examined to date, we found a
      significant positive relationship between elevated serum HCY levels and currently
      experiencing depressive symptoms. Given the cross-sectional nature of the study,
      it is not possible to determine the direction of the relationship or whether
      lowering HCY levels will ameliorate depressive symptoms. Thus, longitudinal
      studies are needed.

PMID- 22480449
TI  - Characterization of stress induced by copper and zinc on cucumber (Cucumis
      sativus L.) seedlings by means of molecular and population parameters.
AB  - Contamination of plants with heavy metals could result in damage in DNA, such as
      mutations and cross-links with proteins. These altered DNA profiles may become
      visible in changes such as the appearance of a new band, or loss of an existing
      band, in the random amplified polymorphic DNA (RAPD) assay. In this study,
      various concentrations of copper and zinc salts were applied to cucumber
      seedlings during germination. Results displayed abnormalities in germination and
      also changes in root elongation, dry weight and total soluble protein level. All
      treatment concentrations (40, 80, 160, 240, 320, and 640mg/L) used in the study
      caused a decrease/delay in germination of the cucumbers to different extents.
      Inhibition or activation of root elongation was considered to be the first effect
      of metal toxicity in the tested plants. Application of the metal salts and the
      combined solutions on cucumber (Cucumis sativus L.) seedlings revealed similar
      consequences for total soluble protein level, dry weight and ultimately in
      inhibitory rates as well. The data obtained from RAPD band-profiles and genomic
      template stability (GTS) showed results that were consistent with the population
      parameters. In this regard, we conclude that molecular marker assays can be
      applied in combination with population parameters to measure genotoxic effects of
      heavy metals on plants.

PMID- 22480450
TI  - Unusual structure-genotoxicity relationship in mouse lymphoma cells observed with
      a series of kinase inhibitors.
AB  - During development of a novel kinase inhibitor for an anti-inflammatory therapy
      at AstraZeneca UK, the lead compound was found to be potently active in the mouse
      lymphoma assay (MLA). This was not believed to be due to primary pharmacology
      because structural alert relationships and a negative Ames test indicated that
      the compound was unlikely to form DNA adducts. A number of investigations were
      performed to assess whether mammalian cell genotoxicity was inherent to the
      chemical series. The in vitro micronucleus assay (MN(vit)) combined with a semi
      automated analysis system, was used as a high-throughput screen. A number of
      additional compounds were selected for testing, all with different substituents
      around a core isoquinolinone. These modifications did not affect the kinase and
      non-kinase selectivity of the compounds. Several of these compounds were positive
      in the MN(vit), however, two compounds were found to be negative and these were
      also confirmed to be negative in the MLA. It was considered possible that
      topoisomerase II or off-target kinase inhibition may have been responsible for
      the observed mammalian cell genotoxicity. The present investigations show how an
      iterative chemical design, along with genotoxicity screening by use of a semi
      automated MN(vit), can identify and remove the genotoxic hazard from
      pharmaceutical projects at an early stage of development, and produce high
      quality molecules suitable for further progression.

PMID- 22480451
TI  - A synthetic peptide mimic of lambda-Cro shows sequence-specific binding in vitro
      and in vivo.
AB  - Development of small synthetic transcription factors is important for future
      cellular engineering and therapeutics. This article describes the chemical
      synthesis of alpha-amino-isobutyric acid (Aib) substituted, conformationally
      constrained, helical peptide mimics of Cro protein from bacteriophage lambda that
      encompasses the DNA recognition elements. The Aib substituted constrained helical
      peptide monomer shows a moderately reduced dissociation constant compared to the
      corresponding unsubstituted wild type peptide. A suitably cross-linked dimeric
      version of the peptide, mimicking the dimeric protein, recapitulates some of the
      important features of Cro. It binds to the operator site O(R)3, a high affinity
      Cro binding site in the lambda genome, with good affinity and single base-pair
      discrimination specificity. A dimeric version of an even shorter peptide mimic
      spanning only the recognition helix of the helix-turn-helix motif of the Cro
      protein was created following the same design principles. This dimeric peptide
      binds to O(R)3 with affinity greater than that of the longer version. Chemical
      shift perturbation experiments show that the binding mode of this peptide dimer
      to the cognate operator site sequence is similar to the wild type Cro protein. A
      Green Fluorescent Protein based reporter assay in vivo reveals that the peptide
      dimer binds the operator site sequences with considerable selectivity and
      inhibits gene expression. Peptide mimics designed in this way may provide a
      future framework for creating effective synthetic transcription factors.

PMID- 22480452
TI  - Clozapine-induced agranulocytosis in Finland, 1982-2007: long-term monitoring of
      patients is still warranted.
AB  - OBJECTIVE: Recent studies suggest that restrictions on the use of clozapine
      should be reassessed considering the risk-benefit ratio. We analyzed all cases of
      clozapine-induced agranulocytosis reported to the Finnish National Agency for
      Medicines between 1982 and 2007. METHOD: In this retrospective longitudinal
      study, we defined agranulocytosis as a neutrophil count below 0.5 * 109/L and,
      accordingly, identified a total of 163 patients with clozapine-induced
      agranulocytosis. We collected all available information on patient demography, as
      well as on daily clozapine doses, treatment duration, concomitant medication
      prior to the onset of agranulocytosis, and infections during the adverse event.
      The amount of clozapine used annually in Finland was estimated on the basis of
      the defined daily dose, and the frequency of agranulocytosis was calculated from
      the absolute number of cases in relation to the defined daily dose each year, as
      reported by the Finnish National Agency for Medicines. RESULTS: In 10.3% of
      cases, agranulocytosis occurred after the second treatment year, and, in some
      patients, agranulocytosis occurred even after 13, 14, and 22 years of clozapine
      treatment. Strikingly, a total of 40% of all patients and 80% of those with fatal
      agranulocytosis had received, concomitantly with clozapine, other medication
      associated with agranulocytosis. CONCLUSIONS: Some restrictions and long-term
      blood monitoring during the use of clozapine are still needed. In addition, we
      raise the question of whether guidelines for concomitant use of drugs associated
      with agranulocytosis during clozapine therapy are warranted.

PMID- 22480454
TI  - Can the home environment promote resilience for children born very preterm in the
      context of social and medical risk?
AB  - Relationships between the home environment and early developmental outcomes were
      examined in 166 children born very preterm in one tertiary maternity hospital to
      explore whether a more optimal home environment could promote resilience. In
      particular, we explored whether this effect was apparent over and above social
      risk and children's biological risk, as measured by cerebral white matter
      abnormality (WMA) evaluated using magnetic resonance imaging (MRI) at term
      corrected age and length of hospital stay (LOS), and whether the effect of the
      home environment differed according to WMA. The home environment and social
      emotional outcomes were assessed at 2years' corrected age using the Home
      Screening Questionnaire (HSQ) and the Infant-Toddler Social and Emotional
      Assessment (ITSEA). Children's cognitive and motor development was assessed using
      the Bayley Scales of Infant Development II. A more optimal home environment was
      associated with better cognitive and social-emotional development after adjusting
      for social risk, WMA, and LOS. Neonatal cerebral WMA moderated the relationship
      between the home environment and dysregulation problems only, such that the home
      environment had less effect on dysregulation for children with mild or moderate
      to severe WMA. The need to support parents to create an optimal home environment
      is discussed.

PMID- 22480455
TI  - Kinetics of single and dual infection of calves with an Asian atypical bovine
      pestivirus and a highly virulent strain of bovine viral diarrhoea virus 1.
AB  - Atypical bovine pestiviruses related to bovine viral diarrhoea virus (BVDV) have
      recently been detected in cattle from South America, Asia and Europe. The purpose
      of this study was to compare the clinical and virological aspects of dual
      infection with BVDV-1 (Horton 916) and an Asian atypical bovine pestivirus
      (Th/04_KhonKaen) in naive calves, in comparison to single infections. Milder
      clinical signs were observed in the animals infected with single Th/04_KhonKaen
      strain. Leukocytopenia and lymphocytopenia were observed in all infected groups
      at a similar level which correlated with the onset of viraemia. Co-infection with
      both viruses led to prolonged fever in comparison to single strain inoculated
      groups and simultaneous replication of concurrent viruses in blood and in the
      upper respiratory tract. Following the infections all the calves seroconverted
      against homologous strains. Atypical pestiviruses pose a serious threat to
      livestock health and BVDV eradication, since they may have the potential to be
      widely spread in cattle populations without being detected and differentiated
      from other BVDV infections.

PMID- 22480456
TI  - Prostaglandin E2 affects osteoblast biology in a dose-dependent manner: an in
      vitro study.
AB  - OBJECTIVE: This study aimed to determine in vitro how exogenous PGE(2) affects
      the expression of genes in cultured osteoblasts by relative quantitation PCR.
      DESIGN: Cultured osteoblasts were exposed to 10(-3)M, 10(-5)M or 10(-7)M PGE(2)
      over 5, 10, 15 and 20 days. RESULTS: RANKL expression was higher after 5 days of
      exposure (p<0.05), but thereafter reduced in those treated with the two lower
      doses of PGE(2) (p<0.01). RANKL/OPG ratio reported in favour of OPG gene
      expression and alkaline phosphatase gene expression increased in osteoblasts
      exposed to the two lower doses of the eicosanoid after 15 days. Conversely,
      prostaglandin E synthase, a cytokine produced during PGE(2) synthesis, gene
      expression was significantly reduced at 15 and 20 days (p<0.01 and 0.05
      respectively). The results from this study add to the current knowledge of the
      mechanisms by which PGE(2) modulates the osteoblast biology in a dose-dependent
      manner. CONCLUSIONS: It is proposed that PGE(2)at a low dose switch osteoblast's
      biology in favour of bone apposition by: first, inducing a significantly higher
      OPG gene expression overwhelming RANKL gene expression; second, reducing PGEs
      synthesis; and third, increasing ALP gene expression. An opposite effect is
      expected when the concentration of the eicosanoid overpass certain levels.

PMID- 22480457
TI  - Masseter inflammation differentially regulates three nitric oxide synthases in
      the rat trigeminal subnucleus caudalis.
AB  - OBJECTIVE: The aim of the present study was to evaluate changes in expression
      levels of three nitric oxide synthases (NOSs), namely inducible NOS (iNOS),
      neuronal NOS (nNOS) and endothelial NOS (eNOS), in the subnucleus caudalis of the
      trigeminal sensory nuclear complex (Vc) under experimental myositis conditions.
      DESIGN: Male Sprague Dawley rats were injected with an inflammatory agent,
      complete Freund's adjuvant (CFA), or capsaicin in the masseter muscle. The
      brainstem region containing the Vc was extracted at both immediate (30 and 60
      min) and longer (1, 3, 7 days) time points to examine the changes in the three
      NOS protein levels via the Western blot technique. Subsequently, the RT-PCR
      experiments were carried out to verify the changes in iNOS mRNA. RESULTS:
      Following the injections of CFA, there were no significant changes in the level
      of the three NOS proteins at the immediate time points. However, there was a
      significant upregulation of iNOS mRNA and protein 3 days after CFA-induced
      inflammation. Neither nNOS nor eNOS showed significant changes in the protein
      level at any of the longer time points. Capsaicin injection in the masseter,
      which we recently reported to upregulate all three NOS at the immediate time
      points, did not result in significant changes at longer time points. CONCLUSION:
      Acute and chronic muscle inflammation differentially modulates the expression of
      the three NOS in the Vc. These data suggest that the contribution of each NOS in
      craniofacial muscle pain processing under inflammatory conditions may be
      anticipated with distinct temporal profiles.

PMID- 22480458
TI  - Tissue preservation may offer a harm-reduction strategy for men with early
      prostate cancer.

PMID- 22480459
TI  - Botulinum neurotoxin serotype A suppresses neurotransmitter release from afferent
      as well as efferent nerves in the urinary bladder.
AB  - BACKGROUND: Botulinum neurotoxin A (BoNTA), which alleviates overactive bladder
      symptoms, is thought to act predominantly via the inhibition of transmitter
      release from parasympathetic nerves. However, actions at other sites such as
      afferent nerve terminals are possible. OBJECTIVE: To evaluate the effects of
      BoNTA on bladder afferent neuropeptide release and firing. DESIGN, SETTING, AND
      PARTICIPANTS: One side of the bladder of control and chronic (1-2 wk) spinal cord
      transected (SCT; T(8)-T(9)) adult female mice was injected with BoNTA (0.5 U/5
      MUl saline). After 48 h, bladders with L(6)-S(2) spinal nerves were prepared for
      in vitro recordings. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In bladder
      preparations, tension and optical mapping of Ca(2+) transients were used to
      measure intrinsic contractions, those evoked by capsaicin or the electrical
      stimulation of spinal nerves. Afferent firing was evoked by stretch or intrinsic
      bladder contractions. The numbers of responding units and firing rates were
      measured. Animal numbers were used to detect moderate to large between-group
      differences based on Cohen's criteria. Two-way analysis of variance was used to
      test spatial/temporal differences in Ca(2+) signals as mean plus or minus
      standard deviation. Differences between data sets were tested with the student t
      test and skewed data sets with a Mann-Whitney U test (significant when p<0.05).
      RESULTS AND LIMITATIONS: In control and SCT bladders, BoNTA treatment decreased
      the contractions evoked by electrical stimulation of spinal nerves without
      altering intrinsic contractions. Afferent firing on untreated sides in response
      to stretch/intrinsic contractions was increased in SCTs versus controls. On BoNTA
      treated sides, afferent firing rates were greatly attenuated in response to
      mechanical stimulation as were the capsaicin-evoked optical signals mediated by
      neuropeptide release. CONCLUSIONS: SCT caused an increased sensitivity of
      afferent nerves to mechanical stimulation that was reduced by BoNTA treatment.
      Increased intrinsic activity after SCT was unaffected by the toxin. Thus BoNTA
      suppresses neurogenic detrusor overactivity by targeting afferent as well as
      efferent pathways in the bladder.

PMID- 22480460
TI  - The impact of dietary calcium and oxalate ratios on stone risk.
AB  - OBJECTIVE: To determine whether the ratio of dietary calcium and oxalate
      consumption at mealtime affects gastrointestinal oxalate absorption and urinary
      oxalate excretion. METHODS: A study was conducted with 10 non-stone-forming
      adults placed on controlled diets with daily calcium and oxalate contents of 1000
      and 750 mg, respectively. Subjects consumed a balanced calcium/oxalate ratio diet
      for 1 week, observed a minimum 1-week washout period, and subsequently consumed
      an imbalanced calcium/oxalate ratio diet for one week. Urine specimens were
      collected on the last 4 days of each diet. Outcome measures included urinary
      creatinine, calcium, and oxalate as well as the Tiselius index for assessing
      urinary calcium oxalate supersaturation. RESULTS: Total daily calcium excretion,
      oxalate excretion, and Tiselius index were similar between balanced and
      imbalanced dietary phases. There were significant differences in calcium
      excretion (mg/g creatinine) between balanced and imbalanced diets in the 1-6 PM
      (83.1 vs 110.2, P <.04), 6-11 PM (71.3 vs 107.2, P <.02), and 11 PM-8 AM
      collections (55.0 vs 41.8, P <.02). There was significantly higher oxalate
      excretion on the balanced diet in the 1-6 pm time period (28.1 vs 16.7, P <.01).
      There were no differences in the Tiselius index in these collections. CONCLUSION:
      These results demonstrate that the sequence of ingesting relatively large amounts
      of oxalate does not significantly affect calcium oxalate stone risk if the
      recommended daily quantity of dietary calcium is consumed.

PMID- 22480461
TI  - Histopathologic analysis of bladder in patient with cloacal exstrophy.
AB  - We report the case of a newborn infant with cloacal exstrophy. On the 16th day
      after birth, complete primary exstrophy repair was performed. The bladder tissue
      obtained during surgery contained collagen tissue and a little smooth muscle, as
      well as a few neuron cells and kit-positive interstitial cells in the submucosal
      layer. This is the first report of a histopathologic analysis of the bladder
      tissue in cloacal exstrophy. We also discuss the influence of the pathologic
      changes on bladder dysfunction.

PMID- 22480462
TI  - [Arterial hypertension with renal disease revealed by heart failure in infants:
      two case reports].
AB  - While blood pressure measurement methods in infants are well established,
      hypertension, a rare disease in this population, may still be revealed by heart
      failure. Kidney diseases are the most common causes of hypertension, prompting
      the search for a renovascular cause to start appropriate treatment. We report on
      2 cases of late diagnosis of hypertension in infants, with hypertensive
      cardiomyopathy, one in the context of autosomal recessive polycystic kidney
      disease and the other in the context of renal artery stenosis with hemodynamic
      disorder, hypertensive encephalopathy and neurological sequelae. In both cases,
      the equilibrium of blood pressure was difficult to achieve in the acute phase.
      Renal ultrasound is fundamental for diagnosis. The potential complications
      related to hypertension require early diagnosis, emphasizing the importance of
      measuring blood pressure during a routine consultation in infants.

PMID- 22480463
TI  - [Recommendations for pediatric oxygen therapy in acute and chronic settings:
      needs assessment, implementation criteria, prescription practices and follow-up].
AB  - Recommendations for acute and long-term oxygen therapy (needs assessment,
      implementation criteria, prescription practices, and follow-up) in children were
      produced by the Groupe de Recherche sur les Avancees en Pneumo-Pediatrie (GRAPP)
      under the auspices of the French Paediatric Pulmonology and Allergology Society
      (SP2A). The Haute Autorite de Sante (HAS) methodology, based on the Formalized
      Consensus, was used. A first panel of experts analyzed the English and French
      literature to provide a second panel of experts with recommendations to validate.
      Only the recommendations are presented here, but the full text
      (arguments+recommendations) is available at the website of the French Paediatric
      Society: www.sfpediatrie.com.

PMID- 22480464
TI  - [Creation and report of the Tunisian Fanconi Anemia Registry (TFAR)].
AB  - INTRODUCTION: Fanconi anemia (FA) is a genetically and phenotypically
      heterogeneous inherited disease. Many groups have established FA registries. In
      Tunisia, in collaboration with the Tunisian Fanconi Anemia Study Group (TFASG),
      we set up the Tunisian Fanconi Anemia Registry (TFAR). PATIENTS AND METHODS: We
      contacted all hematology and pediatrics departments to include their FA patients
      diagnosed between January 1983 and December 2008. The registry is available on
      the TFASG web site (www.fanconi-tunisie.net). RESULTS: Sorting the files brought
      out 142 patients belonging to 118 families. The mean age at diagnosis was 11
      years. There was consanguinity in 86%, malformative syndrome in 91%, and
      pancytopenia at diagnosis in 69%. Of 28 patients, 95% belonged to the FANCA
      group. Androgen treatment was given in 109 cases and genoidentical bone marrow
      transplantation (BMT) in 27 patients. The diagnosis of a myelodysplastic syndrome
      was retained in 4%, acute leukemia in 6%, and a solid tumor in 2%. The median
      overall survival time in all patients is 17 years 5 months; it is significantly
      better in patients having received allografts (p=0.01). CONCLUSION: FA seems
      frequent in Tunisia, which is in part explained by the high consanguinity and
      endogamy in this country. Hematologic impairment is still the most frequent
      revealing circumstance of the disease. It is often severe or moderate and
      requires androgen treatment or bone marrow transplantation. BMT should be
      proposed to all patients with an HLA-compatible donor.

PMID- 22480465
TI  - [Neuroimaging in pediatric epilepsy].
AB  - The main causes of epilepsy in children are cortical malformations
      (hemimegalencephaly, cortical dysplasia, lissencephaly, etc.) and phakomatosis
      (tuberous sclerosis, Sturge-Weber disease, neurofibromatosis type 1, etc.),
      perinatal ischemia, traumatisms, infections, mesial temporal sclerosis, metabolic
      diseases, and tumors. Imaging indications are precise, including partial seizures
      and a pathological electroencephalogram. Twenty-five percent of these epilepsy
      cases are pharmacoresistant. Indeed, MRI is essential to consider surgical
      treatment, allowing one to localize potential epileptogenic anatomic lesions. The
      protocol includes sequences in three planes of space, weighted in T1, T2, Flair,
      T1 inversion-recovery, and T1 after gadolinium injection. MRI findings are
      characteristic for some tumors, but most malformations are subtle. Consequently
      recent techniques (spectroscopy, diffusion, etc.) are crucial when conventional
      MRI is not sufficient. The aim of this article is to illustrate, with a
      substantive image revue, this wide diversity of etiologies in pediatric epilepsy,
      in order to help the attendee recognize MRI findings, also discussing the role of
      newer imaging modalities in this field.

PMID- 22480466
TI  - Articular cartilage development: a molecular perspective.
AB  - In this article, development of articular cartilage and endochondral ossification
      is reviewed, from the perspective of both morphologic aspects of histogenesis and
      molecular biology, particularly with respect to key signaling molecules and
      extracellular matrix components most active in cartilage development. The current
      understanding of the roles of transforming growth factor beta and associated
      signaling molecules, bone morphogenic proteins, and molecules of the Wnt-beta
      catenin system in chondrogenesis are described. Articular cartilage development
      is a highly conserved complex biological process that is dynamic and robust in
      nature, which proceeds well without incident or failure in all joints of most
      young growing individuals.

PMID- 22480468
TI  - Effect of exercise on articular cartilage.
AB  - This review primarily focuses on how the macromolecular composition and
      architecture of articular cartilage and its unique biomechanical properties play
      a pivotal role in the ability of articular cartilage to withstand mechanical
      loads several magnitudes higher than the weight of the individual. Current
      findings on short-term and long-term effects of exercise on human articular
      cartilage are reviewed, and the importance of appropriate exercises for
      individuals with normal and diseased or aberrated cartilage is discussed.

PMID- 22480469
TI  - Imaging of osteochondritis dissecans.
AB  - Osteochondritis dissecans (OCD) is a localized process that affects the
      subchondral bone and can progress to the overlying articular cartilage. The cause
      of this lesion remains elusive. With the vague clinical symptoms and signs of
      OCD, imaging plays a vital role in making the diagnosis and helping with the
      prognosis of OCD lesions. This article reviews current imaging modalities for the
      assessment of OCD including conventional radiography, nuclear medicine, computed
      tomography (CT), CT arthrography, magnetic resonance (MR) and MR arthrography.
      The role of imaging in evaluating healing of the OCD and articular congruity
      after surgical and nonsurgical management is discussed.

PMID- 22480467
TI  - Structural and functional maturation of distal femoral cartilage and bone during
      postnatal development and growth in humans and mice.
AB  - The size and shape of joints markedly affect their biomechanical properties, but
      the macroscopic 3-dimensional (3-D) mechanism and extent of cartilage and joint
      maturation during normal growth are largely unknown. This study qualitatively
      illustrates the development of the bone-cartilage interface in the knee during
      postnatal growth in humans and C57BL/6 wild-type mice, quantitatively defines the
      3-D shape using statistical shape modeling, and assesses growth strain rates in
      the mouse distal femur. Accurate quantification of the cartilage-bone interface
      geometry is imperative for furthering the understanding of the macroscopic
      mechanisms of cartilage maturation and overall joint development.

PMID- 22480470
TI  - Epidemiology, pathogenesis, and imaging of arthritis in children.
AB  - Juvenile idiopathic arthritis is a broad term used to describe a series of
      chronic arthritis occurring in children younger than 16 years of age. Even though
      the cause is not fully understood, several clues regarding the pathogenesis have
      been found. Diagnosis of the different types of juvenile idiopathic arthritis is
      made clinically, and imaging plays a role in answering specific questions
      pertaining to disease classification, staging, and outcome of treatment options.

PMID- 22480471
TI  - Acute traumatic and sports-related osteochondral injury of the pediatric knee.
AB  - Adolescents are predisposed to osteochondral (OC) injuries in the knee. The
      medial facet of the patella, the femoral trochlea, and the lateral femoral
      condyle are the most common sites of injury. Most of these injuries are
      classically traumatic but noncontact injuries. Surgery is warranted in most cases
      of OC fracture. Depending on size, condition, and location of the lesion, options
      include OC fragment reduction and internal fixation or excision and cartilage
      resurfacing. Understanding of how to diagnose and treat OC fractures will help
      optimize outcomes.

PMID- 22480472
TI  - "One step" treatment of juvenile osteochondritis dissecans in the knee: clinical
      results and T2 mapping characterization.
AB  - Osteochondritis dissecans (OCD) is an increasingly common cause of knee pain and
      dysfunction among skeletally immature and young adult patients. An ideal
      treatment strategy with an optimal surgical technique to repair the osteochondral
      lesions in these patients is still controversial. The goal of this study is to
      evaluate and report the clinical and MRI findings for the treatment of OCD in the
      pediatric knee with bone marrow-derived cell transplantation by using a one-step
      surgical technique.

PMID- 22480473
TI  - Clinical relevance of scaffolds for cartilage engineering.
AB  - The repair of articular cartilage defects in patients' knees presents a
      particular challenge to the orthopedic surgeon because cartilage lacks the
      ability to repair or regenerate itself. Various cartilage repair techniques have
      not produced a superior or uniform outcome, which has led to a new generation of
      cartilage repair based on tissue-engineering strategies and the use of biological
      scaffolds. Clinical advances have been made regarding the regeneration of
      articular cartilage, and continue to be made toward the achievement of a suitable
      treatment method for resurfacing osteochondral defects, through cartilage tissue
      engineering and the use of pluripotent cells seeded on bio-scaffolds.

PMID- 22480474
TI  - Implantation of orthobiologic, biodegradable scaffolds in osteochondral repair.
AB  - The treatment of articular cartilage lesions is complicated, but novel tissue
      engineering approaches seem to improve the outcome. A tissue engineering approach
      is less invasive and reduces surgical time, periosteal hypertrophy, and
      morbidity. Cell-based therapies using scaffolds have advantages compared with
      microfracture techniques, but the efficacy and cost-effectiveness need to be
      investigated. Second-generation cell-based therapies have lower morbidity and the
      ease of the technique is not significantly different from that of first
      generation autologous chondrocyte implantation techniques. Third-generation cell
      based therapies such as the use of tissue engineered scaffolds need to be studied
      in more detail.

PMID- 22480475
TI  - Cartilage injuries in the pediatric knee. Preface.

PMID- 22480476
TI  - Comparative studies on the interactions of honokiol and magnolol with human serum
      albumin.
AB  - In this study, the binding modes of honokiol (HK) and magnolol (MG) with human
      serum albumin (HSA) have been established under imitated physiological condition,
      which was very important to understand the pharmacokinetics and toxicity of HK or
      MG. The experimental results proved that the fluorescence of HSA was quenched by
      HK or MG through a static quenching procedure. The binding constants of HK-HSA
      and MG-HSA complexes were 5.304 and 263.755*10(4) L mol(-1) at 298 K,
      respectively. The binding process was a spontaneous molecular interaction
      procedure, in which the hydrophobic interaction played a major role in the
      formation of the HK-HSA complex, whereas, the binding interaction between MG and
      HSA might involve the hydrophobic interaction strongly and electrostatic
      interaction. In addition, the effect of HK/MG on the secondary structure of HSA
      was analyzed using CD, UV-vis absorption, Fourier transform infrared (FT-IR),
      synchronous fluorescence and three-dimensional fluorescence spectra. According to
      Forster no-radiation energy transfer theory, the binding distance of HSA to HK or
      MG was calculated to be 1.842 or 1.238 nm. Besides, the effects of common ions on
      the binding constants of HSA-HK/MG systems were also discussed.

PMID- 22480477
TI  - Comparison of solid phase microextraction versus spectroscopic techniques for
      binding studies of carbamazepine.
AB  - The binding of carbamazepine to human serum albumin was studied in vitro using
      solid-phase microextraction (SPME) with liquid chromatography-ultraviolet
      detection (LC-UV), as well as spectroscopic fluorescence and nuclear magnetic
      resonance ((1)H NMR) techniques. We were able to recognize one high affinity
      binding site with both fluorescence and SPME methods. Additionally, SPME
      experiment showed the existence of one lower affinity binding site for
      carbamazepine at the range of concentrations studied with fluorescence. The
      analysis of Hill's plot indicated positive cooperativity between drugs located in
      these two binding sites. Two low affinity-binding sites have been found with SPME
      LC-UV analysis performed in parallel to (1)H NMR study, which does not show any
      complex formation. In conclusion, the results of the studies with carbamazepine
      as a model drug showed the advantages of simultaneous use of solid phase
      microextraction and spectroscopic methods in protein binding studies and
      indicated complementary information, which can be obtained with the use of SPME.
      Furthermore, we show that SPME in combination with liquid chromatography-mass
      spectrometry permitted direct in vitro determination of plasma-protein binding
      and direct in vivo evaluation of inter-animal variability in free concentrations
      of carbamazepine at physiologically relevant concentrations, the type of
      experiments typically inaccessible by spectroscopic techniques due to poor
      sensitivity and different mode of implementation.

PMID- 22480478
TI  - Role of endothelial shear stress in stent restenosis and thrombosis:
      pathophysiologic mechanisms and implications for clinical translation.
AB  - Restenosis and thrombosis are potentially fatal complications of coronary
      stenting with a recognized multifactorial etiology. The effect of documented risk
      factors, however, cannot explain the preponderance of certain lesion types, stent
      designs, and implantation configurations for the development of these
      complications. Local hemodynamic factors, low endothelial shear stress (ESS) in
      particular, are long known to critically affect the natural history of
      atherosclerosis. Increasing evidence now suggests that ESS may also contribute to
      the development of restenosis and thrombosis upon stenting of atherosclerotic
      plaques, in conjunction with well-appreciated risk factors. In this review, we
      present in vivo and mechanistic evidence associating ESS with the localization
      and progression of neointimal hyperplasia and in-stent clotting. Clinical studies
      have associated stent design features with the risk of restenosis. Importantly,
      computational simulations extend these observations by directly linking specific
      stent geometry and positioning characteristics with the post-stenting hemodynamic
      milieu and with the stent's thrombogenicity and pro-restenotic potential, thereby
      indicating ways to clinical translation. An enhanced understanding of the
      pathophysiologic role of ESS in restenosis and thrombosis might dictate
      hemodynamically favorable stent designs and deployment configurations to reduce
      the potential for late lumen loss and thrombotic obstruction. Recent
      methodologies for in vivo ESS profiling at a clinical level might allow for early
      identification of patients at high risk for the development of restenosis or
      thrombosis and might thereby guide individualized, risk-tailored treatment
      strategies to prevent devastating complications of endovascular interventions.

PMID- 22480479
TI  - Transcatheter harvest of a dislocated sapien valve with an Inoue balloon through
      the left subclavian artery.

PMID- 22480481
TI  - Coronary atherosclerosis and quantitative myocardial perfusion: a relationship
      beyond stenosis.

PMID- 22480482
TI  - Motion versus flow as a possible nibus for atrial fibrillation.

PMID- 22480484
TI  - Limitations of noninvasive measurement of fractional flow reserve from coronary
      computed tomography angiography.

PMID- 22480486
TI  - Fractional flow reserve estimation by coronary computed tomography angiography.

PMID- 22480488
TI  - A hungry thrombus.

PMID- 22480489
TI  - Dietary energy density and body weight in adults and children: a systematic
      review.
AB  - Energy density is a relatively new concept that has been identified as an
      important factor in body weight control in adults and in children and
      adolescents. The Dietary Guidelines for Americans 2010 encourages consumption of
      an eating pattern low in energy density to manage body weight. This article
      describes the systematic evidence-based review conducted by the 2010 Dietary
      Guidelines Advisory Committee (DGAC), with support from the US Department of
      Agriculture's Nutrition Evidence Library, which resulted in this recommendation.
      An update to the committee's review was prepared for this article. PubMed was
      searched for English-language publications from January 1980 to May 2011. The
      literature review included 17 studies (seven randomized controlled trials, one
      nonrandomized controlled trial, and nine cohort studies) in adults and six cohort
      studies in children and adolescents. Based on this evidence, the 2010 Dietary
      Guidelines Advisory Committee concluded that strong and consistent evidence in
      adults indicates that dietary patterns relatively low in energy density improve
      weight loss and weight maintenance. In addition, the committee concluded that
      there was moderately strong evidence from methodologically rigorous longitudinal
      cohort studies in children and adolescents to suggest that there is a positive
      association between dietary energy density and increased adiposity. This review
      supports a relationship between energy density and body weight in adults and in
      children and adolescents such that consuming diets lower in energy density may be
      an effective strategy for managing body weight.

PMID- 22480490
TI  - Sleep-dependent memory consolidation in patients with sleep disorders.
AB  - Sleep can improve the off-line memory consolidation of new items of declarative
      and non-declarative information in healthy subjects, whereas acute sleep loss, as
      well as sleep restriction and fragmentation, impair consolidation. This suggests
      that, by modifying the amount and/or architecture of sleep, chronic sleep
      disorders may also lead to a lower gain in off-line consolidation, which in turn
      may be responsible for the varying levels of impaired performance at memory tasks
      usually observed in sleep-disordered patients. The experimental studies conducted
      to date have shown specific impairments of sleep-dependent consolidation overall
      for verbal and visual declarative information in patients with primary insomnia,
      for verbal declarative information in patients with obstructive sleep apnoeas,
      and for visual procedural skills in patients with narcolepsy-cataplexy. These
      findings corroborate the hypothesis that impaired consolidation is a consequence
      of the chronically altered organization of sleep. Moreover, they raise several
      novel questions as to: a) the reversibility of consolidation impairment in the
      case of effective treatment, b) the possible negative influence of altered prior
      sleep also on the encoding of new information, and c) the relationships between
      altered sleep and memory impairment in patients with other (medical, psychiatric
      or neurological) diseases associated with quantitative and/or qualitative changes
      of sleep architecture.

PMID- 22480491
TI  - Relative frequency of congenital muscular dystrophy subtypes: analysis of the UK
      diagnostic service 2001-2008.
AB  - The Dubowitz Neuromuscular Centre is the UK National Commissioning Group referral
      centre for congenital muscular dystrophy (CMD). This retrospective review reports
      the diagnostic outcome of 214 UK patients referred to the centre for assessment
      of 'possible CMD' between 2001 and 2008 with a view to commenting on the variety
      of disorders seen and the relative frequency of CMD subtypes in this patient
      population. A genetic diagnosis was reached in 53 of 116 patients fulfilling a
      strict criteria for the diagnosis of CMD. Within this group the most common
      diagnoses were collagen VI related disorders (19%), dystroglycanopathy (12%) and
      merosin deficient congenital muscular dystrophy (10%). Among the patients
      referred as 'possible CMD' that did not meet our inclusion criteria, congenital
      myopathies and congenital myasthenic syndromes were the most common diagnoses. In
      this large study on CMD the diagnostic outcomes compared favourably with other
      CMD population studies, indicating the importance of an integrated clinical and
      pathological assessment of this group of patients.

PMID- 22480494
TI  - Design and synthesis of new 4-pyrazolin-3-yl-1,2,3-triazoles and 1,2,3-triazol-4
      yl-pyrazolin-1-ylthiazoles as potential antimicrobial agents.
AB  - New pyrazolyl-1,2,3-triazoles and 1,2,3-triazol-4-yl-pyrazolylthiazoles were
      synthesized through multi step reactions using 1-tolylyl-4-acetyl-5-methyl-1,2,3
      triazole as a precursor. All the newly synthesized compounds were characterized
      by spectral and elemental analyses. The structure of 11b was evidenced by X-ray
      crystallographic study. The newly synthesized compounds were evaluated for their
      antimicrobial activities and also their minimum inhibitory concentration (MIC)
      against most of test organisms was performed. Amongst the tested compounds 5a,
      5c, 11b and 11c displayed excellent antimicrobial activity.

PMID- 22480493
TI  - Novel pH-sensitive cationic lipids with linear ortho ester linkers for gene
      delivery.
AB  - In an effort to develop pH-sensitive lipoplexes for efficient gene delivery, we
      report three novel cationic lipids containing a linear ortho ester linker that
      conjugates either the headgroup (Type I) or one hydrocarbon chain (Type II) with
      the rest of the lipid molecule. The cationic lipids carry either an iodide or a
      chloride counterion. Compared to our previously reported cyclic ortho ester
      linker, the linear ortho ester linker facilitated the construction of cationic
      liposomes and lipoplexes with different helper lipids. The chloride counterion
      not only facilitated the hydration of the lipid films during liposome
      construction, but also enhanced the hydrolysis of the ortho ester linker in the
      lipoplexes. After incubation at endosomal pH 5.5, the Type I lipoplexes
      aggregated and destabilized the endosome-mimicking model liposomes, but not the
      Type II lipoplexes. The helper lipids (DOPE or cholesterol) of the lipoplexes
      enhanced the pH-sensitivity of the Type I lipoplexes. In CV-1 cells (monkey
      kidney fibroblast), the Type I ortho ester-based lipoplexes, especially those
      with the chloride counterion, significantly improved the gene transfection
      efficiency, in some cases by more than 100 fold, compared to their pH-insensitive
      counterparts consisting of DOTAP. The gene transfection efficiency of the ortho
      ester-based lipoplexes was well correlated with their rate of aggregation and
      membrane destabilization in response to the endosomal pH 5.5.

PMID- 22480495
TI  - GnRH-III based multifunctional drug delivery systems containing daunorubicin and
      methotrexate.
AB  - Here we report on the design, synthesis and biochemical characterization of
      multifunctional bioconjugates containing two chemotherapeutic agents,
      daunorubicin and methotrexate, coupled to the GnRH-III decapeptide, which served
      as a targeting moiety. This represents a possible approach to increase the
      receptor mediated tumor targeting and consequently the cytostatic effect of
      anticancer drug-peptide bioconjugates. The multifunctional bioconjugates were
      prepared according to two drug design approaches recently developed by our group.
      Both bifunctional GnRH-III derivatives, [(4)Lys]-GnRH-III (Glp-His-Trp-Lys-His
      Asp-Trp-Lys-Pro-Gly-NH(2)) and [(8)Lys(Lys)]-GnRH-III (Glp-His-Trp-Ser-His-Asp
      Trp-Lys(Lys)-Pro-Gly-NH(2)), contain two free amino groups suitable for the
      attachment of two anticancer drugs, such as methotrexate and daunorubicin. The
      drugs were chosen with respect to their different mechanisms of action, with the
      goal of increasing the antitumor effect of the bioconjugates. The in vitro
      cytostatic effect of the bioconjugates was determined on MCF-7 human breast, HT
      29 human colon and LNCaP human prostate cancer cells by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay. Their in vitro stability/degradation
      in human serum and in the presence of rat liver lysosomal homogenate was
      investigated by liquid chromatography in combination with mass spectrometry. The
      influence of the multifunctional bioconjugates on the cell adhesion and cell
      proliferation was studied on Mono Mac 6 human leukemic monocytes. It was found
      that (1) all synthesized bioconjugates had in vitro cytostatic effect; (2) they
      were stable in human serum for at least 24 h; (3) they were hydrolyzed in the
      presence of lysosomal homogenate and (4) they exerted a moderate cell-cell
      adhesion inducing effect. These results demonstrate that multifunctional
      bioconjugates containing two different anticancer drugs attached to the same GnRH
      III targeting moiety could be successfully prepared and resulted in higher in
      vitro cytostatic effect than the monofunctional bioconjugates containing either
      methotrexate or daunorubicin, in particular on HT-29 human colon cancer cells.

PMID- 22480496
TI  - OKB, a novel family of brain-gut neuropeptides from insects.
AB  - In insects, neuropeptides play a central role in the control of most
      physiological processes. The knowledge and characterization of new neuropeptide
      families, is of interest on the fields of Genetics, Genomics, Neurobiology,
      Endocrinology and Evolution. This knowledge also provides the tools for the
      design of peptidomimetics, pseudopeptides or small molecules, capable of
      disrupting the physiological processes regulated by the signaling molecules and
      their receptors. This is a promising target for a novel generation of
      insecticides. Using database searches, mass spectrometry and RACE-PCR, we
      identified a neuropeptide precursor transcript encoding a new family of insect
      neuropeptides in the hemipteran Rhodnius prolixus. We named this precursor
      Orcokinin B, because is originated by the alternative splicing of the Orcokinin
      gen. EST and genomic data suggests that Orcokinin B is expressed in the nervous
      system and gut from several insect species, with the exception of Drosophila sp.
      (Diptera) and Acyirthosiphon pisum (Hemiptera). Mass spectrometry and RT-PCR
      confirmed the expression of Orcokinin B in brain and anterior midgut of R.
      prolixus. Furthermore, we identified orthologues of this new family of peptides
      in genomic and EST databases from Arachnids and Crustaceans.

PMID- 22480497
TI  - The radiologic relationship of the shoulder girdle to the thorax as an aid in
      diagnosing neurogenic thoracic outlet syndrome.
AB  - PURPOSE: Neurogenic thoracic outlet syndrome (NTOS) is produced by compression of
      the brachial plexus in the thoracic outlet. The lower position of the shoulder
      girdle relative to the upper thorax may be related to NTOS. We investigated this
      hypothesis using plain cervical radiographs. METHODS: We conducted this case
      control study using plain cervical anteroposterior and lateral radiographs in 63
      NTOS patients and 126 carpal tunnel syndrome patients who were matched for age
      and sex. To estimate the position of the shoulder girdle relative to the upper
      thorax, we analyzed the level of the clavicle using 2 parameters: the number of
      vertebrae visible in a lateral radiograph and the number of vertebrae above the
      line connecting both sternal ends of the clavicles in an anteroposterior
      radiograph. The number of vertebrae visible in a lateral radiograph was the
      parameter for the level of the lateral part of the clavicle relative to the upper
      thorax, whereas we used the number of vertebrae above the line connecting both
      sternal ends of the clavicles in an anteroposterior radiograph to determine the
      level of the medial part of the clavicle. RESULTS: Both parameters were greater
      in the NTOS group than in the control group, which suggests that the level of the
      shoulder girdle was lower in the NTOS group than in the control group. In
      addition, the risk of NTOS was increased in patients with lower shoulder girdle
      position. CONCLUSIONS: The lower placement of the shoulder girdle relative to the
      upper thorax was related to NTOS. Physicians may be able to estimate the position
      of the shoulder girdle using plain cervical radiographs when NTOS is clinically
      suspected. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

PMID- 22480498
TI  - Repair of distal biceps ruptures.

PMID- 22480499
TI  - Three-dimensional computed tomographic analysis of 11 scaphoid waist nonunions.
AB  - PURPOSE: To virtually assess nonunions of the scaphoid waist using 3-dimensional
      computed tomography (CT) reconstruction for the amount of displacement of the
      distal fragment and the postfracture reduction position using the intact opposite
      scaphoid for reference. METHODS: We generated 3-dimensional reconstructions for
      11 nonunions of the scaphoid waist and the contralateral intact scaphoids based
      on CT. The mean age of the patients was 25 years and the time from injury to the
      CT scan was 2.4 years. We used the mirrored 3-dimensional model of the healthy
      scaphoid to guide virtual reduction of the nonunion and calculated the amount of
      displacement of the distal pole fragment from prereduction to postreduction. We
      compared the results with the intrascaphoid angles calculated using single CT
      slices. RESULTS: The scaphoid nonunions showed a mean flexion deformity of 23
      degrees , an ulnar deviation of 5 degrees , and a pronation deformity of 10
      degrees . Mean translation was 0.9 mm volarward, 0.2 mm radialward, and 3.3 mm
      distalward. After reduction, all scaphoids showed a bony overlap on the
      dorsoradial side; the mean volume of this region was 3% of total bone volume.
      There was no correlation between the degree of displacement and the intrascaphoid
      angle measurements. CONCLUSIONS: Preoperative planning for scaphoid
      reconstruction is usually performed using conventional radiographs and single CT
      slices. However, by synthesizing the information from the CT into a 3-dimensional
      reconstruction, an exact analysis is possible. This method also allows
      quantification of prosupination displacement. The postreduction area of dorsal
      bone overlap may be due to appositional callus formation. CLINICAL RELEVANCE:
      Simple volar opening of the scaphoid allows correction of angulation deformities
      but results in lengthening of the scaphoid. Correct reduction of the scaphoid
      fragments is often only possible if the dorsal appositional callus is resected.

PMID- 22480500
TI  - Comparison of 4 fluoroscopic views for dorsal cortex screw penetration after
      volar plating of the distal radius.
AB  - PURPOSE: To determine whether use of the dorsal tangential view improves the
      diagnostic accuracy of intraoperative fluoroscopy compared with conventional
      views in detecting dorsal screw penetrations during volar distal radius plating.
      METHODS: Dorsal cortices of 10 cadaveric distal radii were penetrated in each of
      the second, third, and fourth dorsal extensor compartments at 0, 1, 2, and 3 mm
      penetration. We obtained 4 standardized fluoroscopic images of the wrist:
      lateral, supination, pronation, and dorsal tangential views. Using high
      definition digital images, 2 observers blinded to the experimental paradigm
      determined whether screws were penetrating the dorsal cortex. RESULTS: For screws
      that penetrated the floor of the second dorsal compartment, the 45 degrees 
      supination view was 92% sensitive for detecting screw penetration of 2 mm, and
      98% for 3 mm. For screws that penetrated the third dorsal compartment, the
      lateral view was 68% and 80% sensitive in detecting screw penetrations of 1 and 2
      mm, respectively. However, the dorsal tangential view showed 95% sensitivity for
      1 mm and 98% for 2 mm penetrations. On the floor of the fourth dorsal
      compartment, pronation and dorsal tangential views were both 88% sensitive for 1
      mm screw penetration and 90% and 93% for 2 mm, respectively. CONCLUSIONS: The
      standard lateral view of the wrist failed to detect all screw penetrations. The
      dorsal tangential view increased the accuracy of detecting screw penetrations on
      the floor of the third dorsal compartment, whereas we needed oblique views to
      detect screw penetrations on the floors of second and fourth dorsal compartments.
      CLINICAL RELEVANCE: Routine clinical use of the dorsal tangential view has the
      potential to increase accuracy in detecting dorsal screw penetration during volar
      plating of the distal radius.

PMID- 22480501
TI  - Elbow kinematics after radiocapitellar arthroplasty.
AB  - PURPOSE: Radiocapitellar arthroplasty has been proposed as a reconstructive
      option for combined radial head and capitellar deficiency. The purpose of this
      study was to assess the impact of radiocapitellar replacement on elbow
      kinematics. We hypothesized that with the medial collateral ligament (MCL)
      intact, radiocapitellar arthroplasty would replicate normal kinematics, and that
      a radiocapitellar arthroplasty would more closely approximate normal kinematics
      than an elbow with a deficient lateral column or with a deficient MCL. METHODS:
      We tested 7 cadaveric arms in an upper extremity joint simulator. Each arm
      underwent computed tomographic scanning to aid implant size selection and
      computer-assisted implant insertion. We obtained kinematic data using an
      electromagnetic tracking system during elbow flexion. The capitellar and radial
      head implants were placed through an extended lateral epicondylar osteotomy. We
      sectioned the anterior bundle of the MCL, leaving the flexor-pronator mass
      intact. Outcomes of interest were varus-valgus and rotational kinematics of the
      ulnohumeral joint. RESULTS: The radiocapitellar arthroplasty showed no difference
      in kinematics compared with the postosteotomy control. The MCL-deficient elbow
      showed more valgus angulation and more external ulnar rotation than the control
      or radiocapitellar arthroplasty in the pronated, valgus loaded position. The
      deficient lateral column demonstrated increased external ulnar rotation
      kinematics during active elbow flexion. CONCLUSIONS: Radiocapitellar arthroplasty
      can restore normal elbow kinematics with the MCL intact. If the MCL is deficient,
      radiocapitellar arthroplasty does not restore normal kinematics. CLINICAL
      RELEVANCE: Radiocapitellar arthroplasty should be considered in cases of lateral
      column deficiency because it maintains normal elbow kinematics during active
      motion. Whereas radiocapitellar arthroplasty improves the stability of the MCL
      deficient elbow with deficiency of the lateral column, reconstruction of the MCL
      may further improve normal kinematics.

PMID- 22480502
TI  - Reconstruction of totally degloved fingers with a spiraled parallelogram medial
      arm free flap.
AB  - PURPOSE: To investigate the results of resurfacing completely degloved digits
      using a parallelogram free flap from the medial arm in a spiral fashion. METHODS:
      We reviewed the reconstruction of 26 digits in 21 patients with a parallelogram
      free flap from the medial arm in a spiral fashion following a non-replantable
      degloving injury. RESULTS: The sizable perforator was observed consistently in
      the medial arm with 13 of 21 (62%) originating from the superior ulnar collateral
      artery, 6 of 21 (29%) directly from the brachial artery, and 2 of 21 (9%) from
      the superficial brachial artery. All the flaps but one, which sustained partial
      flap loss, survived uneventfully. Total active motion ranged from 93 degrees  to
      145 degrees  and 112 degrees  to 154 degrees  in the cases with and without
      metacarpophalangeal joint involvement, respectively. The static 2-point
      discrimination test varied from 6 to 13 mm. No scar contracture was recorded in
      these patients. All the patients were satisfied with the overall results.
      CONCLUSIONS: Resurfacing the defect in a spiral fashion is a valuable and
      reliable technique for the reconstruction of complete finger degloving injuries.
      The medial arm flap is a good candidate for this procedure, with satisfactory
      functional recovery and good aesthetic restoration. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 22480503
TI  - Anomalous extensor tendons to the long finger: a cadaveric study of incidence.
AB  - PURPOSE: To evaluate the incidence and anatomic insertion sites of extensor medii
      proprius and extensor indicis medii communis tendons to the long finger in
      cadaveric dissection and to describe the insertion of the extensor medii
      proprius. METHODS: Thirty randomly selected adult cadavers, 44 upper extremities,
      were examined for the presence or absence of an anomalous extensor tendon to the
      long finger. If present, tendon origin and insertion sites were documented, and
      the width of the tendon was evaluated. RESULTS: The extensor medii proprius was
      observed in 4 of 44 extremities, an incidence of 9%. The extensor indicis medii
      communis was observed in 7 of 44 extremities, an incidence of 16%. Tendon widths
      for both the extensor medii proprius and extensor indicis medii communis
      specimens ranged from 1.5 to 3.0 mm. CONCLUSIONS: The incidence of an anomalous
      slip of tendon to the long finger might be higher than previously reported, with
      a combined incidence of 25% in this cadaveric study. This anomalous slip can be a
      resource for surgical reconstruction. CLINICAL RELEVANCE: The presence of
      anomalous tendinous slips to the long finger can be easily overlooked.
      Understanding the anatomical relationships, incidence, and donor tendon
      availability of these anomalous tendons might aid with surgical planning.

PMID- 22480504
TI  - Synovial fistula as a complication of recurrent dorsal wrist ganglion excision:
      case report.
AB  - A wrist synovial fistula is rare. The author reports a patient who developed a
      synovial fistula following excision of a recurrent dorsal wrist ganglion.

PMID- 22480505
TI  - Open reduction and temporary internal fixation of a subacute elbow dislocation.
AB  - We present the case of a 61-year-old woman with a subacute elbow dislocation, who
      was referred to our institution 4 weeks after a fall. She was treated with open
      reduction and temporary bridging internal fixation through a posterior approach
      with a limited contact dynamic compression plate. After 4 weeks, the hardware was
      removed. One year postoperatively, the patient had nearly pain-free motion of 20
      degrees  short of full extension and full flexion. Her radiographs showed
      residual incongruity and degenerative arthritis of the elbow.

PMID- 22480506
TI  - Primary hydatid cyst of the scaphoid: case report.
AB  - Hydatid cyst caused by Echinococcus granulosus is a parasitic disease that can
      affect different organs. It is difficult to diagnose and has a tendency to recur.
      Primary bone involvement occurs in 0.5% to 4.0% of all patients with hydatid
      cysts. We present a 31-year-old woman with a primary hydatid cyst in the left
      scaphoid. Despite the availability of advanced imaging and laboratory
      investigation modalities (such as magnetic resonance imaging and serological
      studies) to make an adequate differential diagnosis of a cystic lesion in our
      case, intraoperative clinical suspicion led to the diagnosis. This was followed
      by a successful outcome without recurrence after 12 months.

PMID- 22480507
TI  - Partial extensor carpi radialis longus turn-over tendon transfer for
      reconstruction of the extensor pollicis longus tendon in the rheumatoid hand:
      case report.
AB  - Reconstruction of a distally ruptured extensor pollicis longus tendon in the
      rheumatoid patient generally involves a tendon transfer or intercalary graft. We
      present an alternative technique using the radial half of the extensor carpi
      radialis longus as a turn-over graft. Using the turn-over technique with a half
      slip of the extensor carpi radialis longus avoids the traditional limitations of
      the extensor carpi radialis longus tendon in distal extensor pollicis longus
      tendon repairs and precludes the need for a free tendon graft.

PMID- 22480508
TI  - Proximal interphalangeal joint volar plate configuration in the crimp grip
      position.
AB  - PURPOSE: To study the configuration of the proximal interphalangeal joint volar
      plate (VP) in the crimp grip position (metacarpophalangeal joint at 0 degrees  to
      45 degrees  flexion, proximal interphalangeal joint at 90 degrees  to 100 degrees
      flexion, and distal interphalangeal joint at 0 degrees  to 10 degrees 
      hyperextension) using magnetic resonance imaging techniques in healthy volunteers
      and cadaver fingers and to compare the results with histological sections.
      METHODS: Magnetic resonance imaging was performed on 24 fingers of 8 healthy
      volunteers and 12 fingers of 4 embalmed cadaver hands in the neutral position and
      in the crimp grip position. The translation of the VP body relative to the middle
      phalanx base during finger flexion was measured. In 6 of 12 cadaver specimens, a
      load of 10 N was applied to the flexor tendons to examine how this would affect
      the histological VP fiber configuration. RESULTS: When the flexor tendons were
      under load in the crimp grip position, the volunteers' VP body was translated an
      average of 3.2 mm, and the cadaver fingers' VP body was translated an average of
      3.0 mm, relative to the middle phalanx base in a distal direction. Histological
      analysis of the crimp grip position revealed reversing fibers in the VP insertion
      at the base of the middle phalanx when the flexor tendons were under load and the
      VP body was translated. When no load was applied in the crimp grip position, no
      translation of the VP body occurred. CONCLUSIONS: This article describes a VP
      translation in a distal direction relative to the middle phalanx base in the
      crimp grip position when the flexor tendons are under load. CLINICAL RELEVANCE: A
      more precise knowledge of the histological properties of the proximal
      interphalangeal joint VP during finger flexion can be expected to provide greater
      diagnostic capabilities and can lead to a better comprehension of injuries.

PMID- 22480509
TI  - Distraction plating for the treatment of highly comminuted distal radius
      fractures in elderly patients.
AB  - PURPOSE: To evaluate internal distraction plating for the management of
      comminuted, intra-articular distal radius fractures in patients greater than 60
      years of age at two level 1 trauma centers. We specifically desired to determine
      whether patients would have acceptable results from the clinical standpoint of
      range of motion, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and
      the radiographic measurements of ulnar variance, radial inclination, and palmar
      tilt. Our hypothesis was that distraction plating of comminuted distal radius
      fractures in the elderly would result in acceptable outcomes regarding range of
      motion, DASH score, and radiographic parameters and would, thereby, provide the
      upper extremity surgeon with another option for the treatment of these fractures.
      METHODS: A retrospective review was performed on 33 patients over 60 years of age
      with comminuted distal radius fractures treated with internal distraction plating
      at two level 1 trauma centers. Patients were treated with internal distraction
      plating across the radiocarpal joint. At the time of final follow-up, radiographs
      were evaluated for ulnar variance, radial inclination, and palmar tilt. Range of
      motion, complications, and DASH scores were also obtained. RESULTS: We treated 33
      patients (mean age, 70 y) with distraction plating for comminuted distal radius
      fractures. At final follow-up, all fractures had healed, and radiographs
      demonstrated mean palmar tilt of 5 degrees  and mean positive ulnar variance of
      0.6 mm. Mean radial inclination was 20 degrees . Mean values for wrist flexion
      and extension were 46 degrees  and 50 degrees , respectively. Mean pronation and
      supination were 79 degrees  and 77 degrees , respectively. At final follow-up,
      the mean DASH score was 32. CONCLUSIONS: In the elderly, distraction plating is
      an effective method of treatment for comminuted, osteoporotic distal radius
      fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22480510
TI  - Cholinergic receptors in the murine oviduct: inventory and coupling to
      intracellular calcium concentration.
AB  - AIMS: In the oviduct, muscarinic acetylcholine receptors (MR) are linked with
      motility regulation and nicotinic receptors (nAChR) with ectopic pregnancy. We
      here aimed to determine the repertoire of cholinergic receptor expression in the
      murine oviduct and their functional coupling to regulation of intracellular
      calcium concentration ([Ca(2+)](i)). MAIN METHODS: Cholinergic receptor
      transcripts were assessed by RT-PCR in oviductal segments (ampulla, isthmus,
      uterotubar junction) in all cyclic stages and pregnancy, and in laser
      microdissected samples of epithelium and smooth muscle, nAChR subunit alpha3
      distribution in tissue sections using an appropriate genetic reporter mouse
      strain. [Ca(2+)](i) responses were monitored in ciliated and non-ciliated
      oviductal cells isolated from wild-type and MR subtypes 1 and 3 gene deficient
      mice. KEY FINDINGS: Transcripts for all MR subtypes (M1-M5) are constantly
      expressed whereas there is some variability in nAChR expression from individual
      to individual. The qualitative expression pattern is independent from the
      hormonal status of the animal, except for nAChR alpha7, which is less present
      during pregnancy. The epithelium expresses M1, M3, nAChR alpha7 (data from laser
      assisted microdissection) and nAChR alpha3 (ultrastructural investigation of
      reporter mice). MR dominate over nAChR in increasing [Ca(2+)](i) with being M3
      the major, but not sole subtype driving this effect. The general nAChR inhibitor
      mecamylamine enhances muscarinic and purinergic responses. SIGNIFICANCE: In
      conclusion, the murine oviduct is endowed with a multiplicity of muscarinic and
      nicotinic receptors subtypes that, with respect to regulation of [Ca(2+)](i), are
      inversely linked to each other. The major, but not sole, cholinergic receptor
      driving increase in [Ca(2+)](i) is M3.

PMID- 22480511
TI  - Carvacrol-induced [Ca2+]i rise and apoptosis in human glioblastoma cells.
AB  - AIMS: This study examined whether the essential oil component carvacrol altered
      cytosolic free Ca(2+) level ([Ca(2+)](i)) and viability in human glioblastoma
      cells. MAIN METHODS: The Ca(2+)-sensitive fluorescent dye fura-2 was applied to
      measure [Ca(2+)](i). Cell viability was measured by detecting reagent WST-1.
      Apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. KEY
      FINDINGS: Carvacrol at concentrations of 400-1000 MUM induced a [Ca(2+)](i) rise
      in a concentration-dependent fashion. The response was decreased partially by
      removal of extracellular Ca(2+). Carvacrol-induced Ca(2+) signal was not altered
      by nifedipine, econazole, SK&F96365, and protein kinase C activator phorbol
      myristate acetate (PMA), but was inhibited by the protein kinase C inhibitor
      GF109203X. When extracellular Ca(2+) was removed, incubation with the endoplasmic
      reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone
      (BHQ) abolished carvacrol-induced [Ca(2+)](i) rise. Incubation with carvacrol
      also abolished thapsigargin or BHQ-induced [Ca(2+)](i) rise. Inhibition of
      phospholipase C with U73122 abolished carvacrol-induced [Ca(2+)](i) rise. At
      concentrations of 200-800 MUM, carvacrol killed cells in a concentration
      dependent manner. This cytotoxic effect was not changed by chelating cytosolic
      Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N--tetraacetic acid/acetoxy
      methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that
      carvacrol (200, 400 and 600 MUM) induced apoptosis in a concentration-dependent
      manner. At concentrations of 200, 400 and 600 MUM, carvacrol induced production
      of ROS. SIGNIFICANCE: In human glioblastoma cells, carvacrol induced a
      [Ca(2+)](i) rise by inducing phospholipase C-dependent Ca(2+) release from the
      endoplasmic reticulum and Ca(2+) entry via protein kinase C-sensitive, non store
      operated Ca(2+) channels. Carvacrol induced cell death that might involve ROS
      mediated apoptosis.

PMID- 22480512
TI  - The role of K ATP channels on ischemia-reperfusion injury in the rat testis.
AB  - AIMS: To investigate the participation of K(ATP) channels on the ischemia
      reperfusion (IR)-induced apoptosis in the rat testis. MAIN METHODS: Eight-week
      old male Sprague-Dawley rats were divided into three groups: control and IR rats
      without or with cromakalim (300 MUg/kg intraperitoneally), 30 min before the
      induction of ischemia. The right testicular artery and vein were clamped to
      induce ischemia in the testis. Sixty minutes after the ischemia, a 24h period of
      reperfusion followed. Then, expressions of K(IR)6.1, K(IR)6.2, caspase-3, PARP,
      Fas, FasL, and K(IR)6.1 and K(IR)6.2 mRNAs were investigated by Western blot
      analyses and real-time PCR methods, respectively. Furthermore, testicular tissues
      were processed for histological evaluation and TUNEL staining. KEY FINDINGS:
      Expressions of K(IR)6.1 protein and mRNA were more than 10-fold of those of
      K(IR)6.2 protein and mRNA in the testis. IR significantly increased the
      expressions of K(IR)6.1 protein and mRNA as well as K(IR)6.2 mRNA, caspase-3, and
      TUNEL index in the testis compared to the control. PARP expressions were
      significantly lower in the IR group than those of the control. Histologically,
      severe acute germ cell damage was observed in the IR testis. Treatment with
      cromakalim ameliorated these parameters compared to the non-treated IR group.
      There were no significant differences on Fas, FasL and protein level of K(IR)6.2
      expressions between any of the groups. SIGNIFICANCE: Treatment with cromakalim
      has a protective effect against IR-induced testicular damage via activating
      K(ATP) channels. This is the first study to give evidence for the advantageous
      effect of cromakalim in the germ cell-specific apoptosis induced by testicular
      IR.

PMID- 22480513
TI  - A study on neuroinflammatory marker in brain areas of okadaic acid (ICV) induced
      memory impaired rats.
AB  - AIMS: The aim of the present study is to investigate the status of
      proinflammatory cytokine in the brain of intracerebroventricular (i.c.v.) okadaic
      acid (OKA) induced memory impaired rat. MAIN METHODS: OKA (200 ng)
      intracerebroventricular (i.c.v.) was administered in rats. Memory was assessed by
      Morris water maze test. Biochemical marker of neuroinflammation (TNF-alpha, IL
      beta), total nitrite, mRNA (RT PCR) and protein expression (WB) of iNOS and nNOS
      were estimated in rat brain areas. KEY FINDINGS: OKA caused memory-impairment in
      rats with increased expression of proinflammatory cytokine TNF-alpha and IL-1beta
      and total nitrite in brain regions hippocampus and cortex. The expression of mRNA
      and protein of iNOS was increased while; the expressions were decreased in case
      of nNOS. Pretreatment with antidementic drugs donepezil (5 mg/kg, p.o.) and
      memantine (10 mg/kg, p.o) for 13 days protected i.c.v. OKA induced memory
      impairment and changes in level of TNF-alpha, IL-beta, total nitrite and
      expressions of iNOS and nNOS in OKA treated rat. SIGNIFICANCE: This study
      suggests that neuroinflammation may play a vital role in OKA induced memory
      impairment.

PMID- 22480514
TI  - Comparison of human ETA and ETB receptor signalling via G-protein and beta
      arrestin pathways.
AB  - AIMS: To determine the pharmacology of ET(A)- and ET(B)-mediated beta-arrestin
      recruitment and compare this to established human pharmacology of these receptors
      to identify evidence for endothelin receptor biased signalling and pathway
      specific blockade by antagonists. MAIN METHODS: The ability of ET-1, ET-2, ET-3,
      sarafotoxin 6b and sarafotoxin 6c to activate ET(A) and ET(B)-mediated beta
      arrestin recruitment was determined in CHO-K1 cells. Affinities were obtained for
      ET(A) selective (BQ123, sitaxentan, ambrisentan), ET(B) selective (BQ788) and
      mixed (bosentan) antagonists using ET-1 and compared to affinities obtained in
      competition experiments in human heart and by Schild analysis in human saphenous
      vein. Agonist dependence of affinities was compared for BQ123 and BQ788 in the
      ET(A) and ET(B) beta-arrestin assays respectively. KEY FINDINGS: For beta
      arrestin recruitment, order of potency was as expected for the ET(A) (ET-1>=ET
      2>>ET-3) and ET(B) (ET-1=ET-2=ET-3) receptors. However, at the ET(A) receptor
      sarafotoxin 6b and ET-3 were partial agonists. Antagonism of ET peptides by
      selective and mixed antagonists appeared non-competitive. BQ123, but not BQ788,
      exhibited agonist-dependent affinities. Bosentan was significantly more effective
      an inhibitor of beta-arrestin recruitment mediated by ET(A) compared to the ET(B)
      receptor. In the ET(A) vasoconstrictor assay, ET-1, ET-2 and S6b were equipotent,
      full agonists and antagonists tested behaved in a competitive manner, although
      affinities were lower than predicted from the competition binding experiments in
      left ventricle. SIGNIFICANCE: These data suggest that the pharmacology of ET(A)
      and ET(B) receptors linked to G-protein- and beta-arrestin mediated responses was
      different and bosentan appeared to show bias, preferentially blocking ET(A)
      mediated beta-arrestin recruitment.

PMID- 22480515
TI  - The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306
      (daglutril), inhibits systemic conversion of big endothelin-1 in humans.
AB  - AIMS: Inhibition of neutral endopeptidases (NEP) results in a beneficial increase
      in plasma concentrations of natriuretic peptides such as ANP. However NEP
      inhibitors were ineffective anti-hypertensives, probably because NEP also
      degrades vasoconstrictor peptides, including endothelin-1 (ET-1). Dual NEP and
      endothelin converting enzyme (ECE) inhibition may be more useful. The aim of the
      study was to determine whether SLV-306 (daglutril), a combined ECE/NEP inhibitor,
      reduced the systemic conversion of big ET-1 to the mature peptide. Secondly, to
      determine whether plasma ANP levels were increased. MAIN METHODS: Following oral
      administration of three increasing doses of SLV-306 (to reach an average target
      concentration of 75, 300, 1200 ng ml(-1) of the active metabolite KC-12615), in a
      randomised, double blinded regime, big ET-1 was infused into thirteen healthy
      male volunteers. Big ET-1 was administered at a rate of 8 and 12 pmol kg(-1)min(
      1) (20 min each). Plasma samples were collected pre, during and post big ET-1
      infusion. ET-1, C-terminal fragment (CTF), big ET-1, and atrial natriuretic
      peptide (ANP) were measured. KEY FINDINGS: At the two highest concentrations
      tested, SLV-306 dose dependently attenuated the rise in blood pressure after big
      ET-1 infusion. There was a significant increase in circulating big ET-1 levels,
      compared with placebo, indicating that SLV-306 was inhibiting an increasing
      proportion of endogenous ECE activity. Plasma ANP concentrations also
      significantly increased, consistent with systemic NEP inhibition. SIGNIFICANCE:
      SLV-306 leads to inhibition of both NEP and ECE in humans. Simultaneous
      augmentation of ANP and inhibition of ET-1 production is of potential therapeutic
      benefit in cardiovascular disease.

PMID- 22480516
TI  - Macrophage secretions modulate the steroidogenesis of polycystic ovary in rats:
      effect of testosterone on macrophage pro-inflammatory cytokines.
AB  - AIMS: The macrophage secretions' effect on ovarian steroidogenesis is
      investigated in a polycystic ovary syndrome rat model (PCO rat). The influence of
      testosterone environment on the expression of macrophage pro-inflammatory
      cytokines that participate in ovarian steroidogenesis is studied. MAIN METHODS:
      PCO rats were induced by estradiol valerate. Spleen macrophages were cultured
      with and without testosterone (10(-6) M) and their secretions were used to
      stimulate ovaries from PCO and control rats. Ovarian hormones released and ovary
      mRNA levels of P450 aromatase and 3beta-hydroxysteroid dehydrogenase were
      measured by radioimmunoassay and RT-PCR, respectively. The tumor necrosis factor
      alpha (TNFalpha) and nitric oxide (NO) levels in macrophage culture medium, along
      with the TNFalpha, interleukin (IL)-6, IL-10 and androgen receptors (AR) mRNA
      levels in macrophage cells were determined. KEY FINDINGS: Macrophages from PCO
      rats released more TNFalpha and NO, expressed higher TNFalpha and IL-6, lower AR,
      and no change in IL-10 mRNA levels than control macrophages. TNFalpha, IL-6 and
      AR changes were greater after macrophage testosterone treatment. Macrophage
      secretions from PCO rats stimulated androstenedione and decreased estradiol
      release and ovarian mRNA P450 aromatase expression in PCO rats compared to
      macrophage secretions from control rats. These effects were greater when
      macrophages from PCO rats were treated with testosterone. Ovarian progesterone
      response was unchanged. SIGNIFICANCE: The differential steroidogenic ability of
      macrophage secretions from PCO rats is associated to the in vitro testosterone
      environment. Testosterone, probably acting on macrophage AR, induces a greater
      release of TNFalpha, modifying ovarian response by increasing androstenedione and
      slightly decreasing estradiol without affecting progesterone.

PMID- 22480517
TI  - Endothelin and endothelin receptors in the renal and cardiovascular systems.
AB  - Endothelin-1 (ET-1) is a multifunctional hormone which regulates the physiology
      of the cardiovascular and renal systems. ET-1 modulates cardiac contractility,
      systemic and renal vascular resistance, salt and water renal reabsorption, and
      glomerular function. ET-1 is responsible for a variety of cellular events:
      contraction, proliferation, apoptosis, etc. These effects take place after the
      activation of the two endothelin receptors ET(A) and ET(B), which are present -
      among others - on cardiomyocytes, fibroblasts, smooth muscle and endothelial
      cells, glomerular and tubular cells of the kidney. The complex and numerous
      intracellular pathways, which can be contradictory in term of functional response
      depending on the receptor type, cell type and physiological situation, are
      described in this review. Many diseases share an enhanced ET-1 expression as part
      of the pathophysiology. However, the use of endothelin blockers is currently
      restricted to pulmonary arterial hypertension, and more recently to digital
      ulcer. The complexity of the endothelin system does not facilitate the
      translation of the molecular knowledge to clinical applications. Endothelin
      antagonists can prevent disease development but secondary undesirable effects
      limit their usage. Nevertheless, the increasing understanding of the effects of
      ET-1 on the cardiac and renal physiology maintains the endothelin system as a
      promising therapeutic target.

PMID- 22480518
TI  - A new clinical approach: use of blood-derived stem cells (BDSCs) for superficial
      digital flexor tendon injuries in horses.
AB  - AIMS: In this study, we present an innovative therapy using stem cells that were
      obtained from the peripheral blood of racehorses affected by uninduced
      superficial digital flexor tendon (SDFT) injuries. MAIN METHODS: Blood-derived
      stem cells (BDSCs) were generated from the blood samples of three horses in the
      presence of macrophage colony-stimulating factor (M-CSF). The racehorses received
      a single autologous BDSC treatment, which resulted in the successful repair of
      the tendons injuries. KEY FINDINGS: The results demonstrated that the BDSCs
      injection into the damaged tendon stimulated the regeneration of normal tissue.
      Furthermore, a relationship may exist between the speed and the quality of new
      tissue formation and the welfare and management of the treated animals.
      SIGNIFICANCE: This study demonstrates that stem cell technology offers new tools
      for tissue repair that in many cases is considered incurable, and provides
      additional evidence that BDScs injections increase the speed and quality of the
      regeneration process in different animal tissues.

PMID- 22480519
TI  - EGCG inhibits Tat-induced LTR transactivation: role of Nrf2, AKT, AMPK signaling
      pathway.
AB  - AIMS: Transcription is a crucial step for human immunodeficiency virus 1 (HIV-1)
      gene expression in infected host cells. The HIV-1 Tat activates the nuclear
      factor-kappa B (NF-kappaB) signaling transduction pathway, which is necessary for
      viral replication. Epigallocatechin-3-gallate (EGCG) has antioxidant, anti
      inflammatory, and anti-viral properties. In this study, we investigated the
      effects of EGCG on Tat-induced HIV-1 transactivation and potential mechanisms by
      which EGCG inhibited activation of NF-kappaB pathway. MAIN METHODS: HeLa-CD4-long
      terminal repeat (LTR)-beta-gal (MAGI) cells were transfected with Tat plasmid.
      Tat-induced HIV-1 LTR transactivation was determined by MAGI cell assay. The
      reactive oxygen species (ROS) levels and glutathione (GSH) levels were measured.
      In addition, the protein expressions were assayed by western blotting. KEY
      FINDINGS: Tat caused a significant decrease in the intracellular glutathione
      (GSH) levels, a mild increase in the expression of nuclear levels of NF-E2
      related factor-2 (Nrf2), a significant increase in the levels of NF-kappaB
      (phosphorylation of p65 and IKK) and a significant increase in ROS production.
      EGCG supplementation significantly improved the changes associated with Tat
      induced oxidative stress by increasing nuclear levels of Nrf2, decreasing levels
      of NF-kappaB and ROS production. EGCG reversed Tat-mediated AKT activation and
      AMPK inhibition in MAGI cells. EGCG inhibited Tat-induced LTR transactivation in
      a dose-dependent manner. SIGNIFICANCE: The results suggest that Nrf2 signaling
      pathway may be the primary target for prevention of Tat-induced HIV-1
      transactivation by EGCG, and EGCG also reduce NF-kappaB activation by inhibiting
      AKT signaling pathway and activating AMPK signaling pathway.

PMID- 22480520
TI  - The endothelin A receptor and epidermal growth factor receptor signaling converge
      on beta-catenin to promote ovarian cancer metastasis.
AB  - AIMS: Endothelin A receptor (ET(A)R) and epidermal growth factor receptor (EGFR)
      cross-talk enhances the metastatic potential of epithelial ovarian cancer (EOC)
      cells activating different pathways, including beta-catenin signalling. Here, we
      evaluated beta-catenin as one of ET(A)R/EGFR downstream pathway in the invasive
      behaviour of EOC cells and their therapeutic potential to co-target ET(A)R and
      EGFR. MAIN METHODS: The phosphorylation status and interactions of different
      proteins were analysed by immunoblotting and immunoprecipitation. Reporter
      activity and RT-PCR was used for evaluation of beta-catenin transcriptional
      activity and gene expression. Functional effects were evaluated by gelatin
      zymography and cell invasion assays. An orthotopic model of metastatic human EOC
      in mice was used for in vivo studies. KEY FINDINGS: In EOC cell lines, ET-1
      induced Src-dependent EGFR transactivation, causing tyrosine (Y) phosphorylation
      of beta-catenin at the residue Y654, its dissociation from E-cadherin complexes
      and the accumulation as an active form. This pool of Tyr-beta-catenin relocalised
      to the nucleus promoting its transcriptional activity, and the expression of its
      target genes, such as MMP-2. At functional level, ET-1 and EGFR circuits enhanced
      protease activity and cell invasion. All these effects were significantly
      inhibited by the ET(A)R antagonist, zibotentan, or EGFR inhibitor, gefitinib, and
      are completely blocked by co-addition of both drugs. In vivo, zibotentan
      treatment significantly inhibited metastases, associated with reduced expression
      and activation of MMPs and active beta-catenin, especially when combined with
      gefitinib. SIGNIFICANCE: Altogether these findings provide additional support to
      the potential use of ET(A)R and EGFR blockade as a new therapeutic opportunity
      for EOC treatment.

PMID- 22480521
TI  - Differences between actual and expected leisure activities after total knee
      arthroplasty for osteoarthritis.
AB  - This prospective cohort study determined the type, frequency, intensity, and
      duration of actual vs expected leisure activity among a cohort undergoing total
      knee arthroplasty. Data on actual and expected participation in 36 leisure
      activities were collected preoperatively and at 12 months in 90 patients with
      knee osteoarthritis. Despite high expectations, there were statistically and
      clinically significant differences between actual and expected activity at 12
      months suggesting that expectations may not have been fulfilled. The differences
      were equivalent to walking 14 less miles per week than expected, which is more
      than the amount of activity recommended in national physical activity guidelines.
      Perhaps an educational intervention could be implemented to help patients
      establish appropriate and realistic leisure activity expectations before surgery.

PMID- 22480522
TI  - Total hip arthroplasty using cementless grit-blasted femoral component: a minimum
      10-year follow-up study.
AB  - The grit-blasted cementless Spotorno (CLS) stem, which has excellent survival
      rates up to 10 years, is widely used in total hip arthroplasty (THA). We
      investigated the survivorships of CLS stems in THA at a minimum follow-up of 10
      years and sought to identify factors that influence outcomes. A total of 227 hips
      of 191 patients who underwent cementless THA with a CLS stem were retrospectively
      reviewed at a mean follow-up of 12.3 years. All patients were evaluated
      clinically and radiographically according to implant type and surgery-related and
      patient-related factors. Survivorship was 97.2% when femoral revision for any
      reason was defined as the end point. Femoral revisions were performed in 3 hips
      because of periprosthetic fractures. Survivorship for all hips, using revision
      for any reason as the end point, was 92.6%. Two metal-on-metal THAs were revised
      because of aseptic loosening or osteolysis around the cup. No significant
      differences were evident for type of stem, type of bearing surface, stem
      alignment, or patient-related factors. However, a canal fill index of 80% or less
      was found to affect cortical remodeling, subsidence, and a change in stem
      position of 5 degrees  or more, which indicates that care must be taken not to
      undersize stems. In addition, in view of the revisions performed, bearing
      surfaces appear to importantly influence THA survivorship.

PMID- 22480523
TI  - Change in preoperative expectations in patients undergoing staged bilateral
      primary total knee or total hip arthroplasty.
AB  - The objective of this study was to compare preoperative expectation scores
      between stages in patients with bilateral total knee arthroplasty (TKA) and total
      hip arthroplasty (THA) using intraclass correlation coefficients (ICCs). For
      patients with TKA (57), ICC was 0.449, indicating fair agreement between stages;
      expectations did not change for 31% of patients, whereas 40% had higher and 29%
      had lower expectations. For patients with THA (55), ICC was 0.663, indicating
      moderate agreement; expectations did not change for 42% of patients, whereas 38%
      had higher and 20% had lower expectations. In multivariable analyses controlling
      for first expectation score, second expectation score was associated with better
      Western Ontario McMaster Universities Osteoarthritis Index stiffness score for
      TKA and with worse Western Ontario McMaster Universities Osteoarthritis Index
      function score for patients with THA. For most patients, expectations changed
      between staged bilateral TKA and THA, but the direction of change was not
      uniform.

PMID- 22480524
TI  - The knee adduction moment during gait is associated with the adduction angle
      measured during computer-assisted total knee arthroplasty.
AB  - Computer-assisted surgery can be used to measure 3-dimensional knee function
      during arthroplasty surgery; however, it is unknown if the movement of the knee
      measured during surgery is related to the in vitro, dynamic state of the knee
      joint, specifically the knee adduction moment during gait, which has been related
      to implant migration. The purpose of this study was to determine if the
      preoperative adduction moment is correlated with the knee abduction/adduction
      angle measured intraoperatively. A statistically significant correlation was
      found between the mean (r(2) = 0.59; P = .001) and peak (r(2) = 0.53; P = .003)
      preoperative knee adduction moment and the mean abduction/adduction angle
      measured intraoperatively. The association found in this study suggests the
      potential for incorporating functional information that relates to surgical
      outcome into surgical decision making using computer-assisted surgery.

PMID- 22480525
TI  - Squeaking hip arthroplasties: a tribological phenomenon.
AB  - The clinical incidence of squeaking has been reported with increasing frequency,
      with ceramic-on-ceramic bearings seemingly most affected. This study investigated
      potential causes of squeaking in hard-on-hard hip bearings through 2 sets of
      experimental conditions. Bearing clearance appeared to affect the incidence of
      squeaking in metal-on-metal surface arthroplasties. The addition of third-body
      particles to the interface for total hip arthroplasties also affected the
      incidence of squeaking. In both studies, the incidence of squeaking correlated
      well with elevated friction. The findings of this study suggest that a likely
      cause of squeaking in the hip arthroplasty is adverse tribological conditions
      caused by suboptimal lubrication. There are numerous factors that may cause the
      suboptimal lubrication, and therefore, it is unlikely that an individual cause
      for squeaking will be identified.

PMID- 22480526
TI  - Alignment changes due to incomplete component seating in total knee arthroplasty.
AB  - Mechanical axis restoration remains a primary goal of total knee arthroplasty.
      Incomplete asymmetrical component seating, through intended or unintended
      alterations in surgical technique, changes the component alignment and, thus, the
      overall mechanical axis. Using a trigonometric analysis, it was determined that
      incomplete seating of 1 to 5 mm can alter the coronal alignment by 0.7 degrees 
      to 4.9 degrees , depending on the amount of asymmetry as well as the size of the
      femoral or tibial component. This analysis quantifies the degree of changes
      surgeons should expect when incomplete component seating is encountered
      intraoperatively.

PMID- 22480527
TI  - Leg length change in total hip arthroplasty with subtrochanteric femoral
      shortening osteotomy for Crowe type IV developmental hip dysplasia.
AB  - Primary total hip arthroplasties were performed in 70 hips for the treatment of
      Crowe type IV developmental dysplasia of the hip. The patients were subdivided
      into 2 groups with or without iliofemoral osteoarthritis. Leg length change was
      measured radiographically. Preoperative hip motion was reviewed from medical
      records and defined as either higher or lower motion groups. The leg length
      change in patients without iliofemoral osteoarthritis was significantly greater
      than that in patients with iliofemoral osteoarthritis, and the higher hip motion
      group had greater leg length change in total hip arthroplasty than the lower
      motion group. The current study identifies several features that might help
      predict leg length change during the preoperative planning of total hip
      arthroplasty for Crowe type IV developmental hip dysplasia.

PMID- 22480528
TI  - Inpatient enoxaparin and outpatient aspirin chemoprophylaxis regimen after
      primary hip and knee arthroplasty: a preliminary study.
AB  - Our institution has used a thromboprophylaxis regimen consisting of inpatient
      enoxaparin and outpatient aspirin for patients at standard risk for venous
      thrombosis after hip and knee arthroplasty. We reviewed 500 cases using this
      protocol. Inpatient treatment with enoxaparin averaged 2.75 days, followed by a
      28-day course of aspirin. The overall thrombosis rate was 0.6% (1 deep venous
      thrombosis and 2 pulmonary emboli). Bleeding requiring transfusion of 3 or more
      units of packed red blood cells occurred in 1.8% of the cases. Fifteen infections
      were noted, 14 superficial and 1 deep. This compared favorably with a control
      group of 500 patients using a 14-day course of enoxaparin followed by 14 days of
      aspirin. We believe that a brief course of inpatient enoxaparin and outpatient
      aspirin is a safe and effective form of thromboprophylaxis.

PMID- 22480529
TI  - Case report: incisional hernia as a complication of extreme lateral interbody
      fusion.
AB  - BACKGROUND CONTEXT: Minimal access surgery is becoming more popular for spinal
      fusion because of a lower theoretical risk of complications and shorter
      postoperative recovery period, compared with the traditional open approach. The
      lateral approach uses retroperitoneal transpsoas access to the vertebra,
      obviating the need for an approach surgeon and minimizing muscular disruption,
      thus allowing a quicker recovery. Initial reports of the lateral transpsoas
      procedure described few complications. However, a number of complications have
      subsequently been documented. To our knowledge, there has not been a description
      of an incisional hernia after this approach. PURPOSE: To report the rare
      complication of an incisional hernia after a minimal access lateral transpsoas
      approach for lumbar interbody fusion. STUDY DESIGN: Case report. METHODS: We
      reviewed the hospital charts, radiographs, and intraoperative photographs of a
      patient who underwent a minimally invasive lateral approach lumbar spine fusion
      with a subsequent incisional hernia that necessitated laparoscopic repair.
      RESULTS: A 75-year-old woman with a history of low back and left lower extremity
      pain with radiographic evidence of foraminal stenosis and degenerative
      spondylolisthesis underwent a successful L4-L5 discectomy with an extreme lateral
      interbody fusion via a retroperitoneal transpsoas approach. This was supplemented
      with a posterior minimally invasive surgery instrumented fusion from L4 to L5.
      The patient reported significant improvement in symptoms on initial follow-up,
      however, complained of a prominence over her incision 4 weeks later. An
      incisional hernia was diagnosed and subsequently repaired laparoscopically, from
      which the patient recovered uneventfully. CONCLUSIONS: Postoperative incisional
      hernia after extreme lateral interbody fusion is a complication that has not been
      previously described in the literature but is one that spine surgeons must
      recognize. This case may prompt surgeons to use a more posterior approach to
      avoid this complication. Additionally, direct repair of the transversalis fascia
      is critical to avoiding this complication.

PMID- 22480530
TI  - Fear of movement/(re)injury and activity avoidance in persons with neurogenic
      versus vascular claudication.
AB  - BACKGROUND CONTEXT: Activity avoidance and fear of movement/(re)injury are
      increasingly being recognized as important factors in the rehabilitation of
      persons suffering from chronic low back pain, yet these factors have not been
      thoroughly explored in persons suffering from neurogenic claudication resulting
      from lumbar spinal stenosis. PURPOSE: To determine, compare, and explain
      differences in the degree of fear of movement/(re)injury and activity avoidance
      in persons with neurogenic claudication, vascular claudication, and asymptomatic
      volunteers. STUDY DESIGN: Prospective controlled cohort study at an academic
      medical center. PATIENT SAMPLE: Eighty-two adults aged between 55 and 90 years
      with neurogenic claudication, vascular claudication, or no back and leg symptoms.
      METHODS: Subjects completed a visual analog scale for pain, the Center for
      Epidemiological Studies Depression Scale, the Quebec Back Pain Disability Scale,
      Short Form 36 (SF-36), and the 13-item version of the Tampa Scale for
      Kinesiophobia (Tampa). They were also asked to estimate their maximum walking
      distance. OUTCOME MEASURES: The difference in the level of fear of
      movement/(re)injury and activity avoidance in the two symptomatic populations, as
      well as the predictive validity of self-reported measures such as pain level,
      functional impairment, and depression in determining fear avoidance. RESULTS: The
      total Tampa score was significantly higher in individuals with neurogenic
      claudication (M=31.68; standard deviation [SD]=7.56; N=39) than vascular
      claudication (M=24.07; SD=6.57; N=15) (p=.002), whereas both symptomatic groups
      were significantly different from controls (M=18.71; SD=6.3; N=28) (p<.001 vs.
      neurogenic; p<.05 vs. vascular). Tampa scores were strongly correlated to the
      Center for Epidemiological Studies Depression Scale score (r=0.515; p<.001), SF
      36 Physical Functioning score (r=-0.632; p<.001), and the visual analog scale
      average level of pain in a week (r=0.461; p<.001). Using a standard multiple
      regression model (R2=0.406; F(3,62)=13.47; p<.001), the amount of functional
      impairment, that is, the SF-36 Physical Functioning score, was the strongest
      contributor to the variance in the Tampa total score (beta=-0.371; p=.014). The
      average level of pain did not make a significant or unique contribution in
      predicting the Tampa total score. Functional impairment as measured by the SF-36
      Physical Functioning was strongly correlated with both pain (r=-0.740; p<.001)
      and depression (r=-0.488; p<.001). CONCLUSIONS: Persons with neurogenic
      claudication have important elevations in fear and avoidance, higher than those
      with claudication from another source (vascular insufficiency). The impact of
      fear and avoidance along with other factors such as depression on pain,
      disability, and quality of life for persons with claudication and spinal stenosis
      need to be explored.

PMID- 22480531
TI  - A review of methods for evaluating the quantitative parameters of sagittal pelvic
      alignment.
AB  - BACKGROUND CONTEXT: The sagittal alignment of the pelvis represents the basic
      mechanism for maintaining postural equilibrium, and a number of methods were
      developed to assess normal and pathologic pelvic alignments from two-dimensional
      sagittal radiographs in terms of positional and anatomic parameters. PURPOSE: To
      provide a complete overview of the existing methods for quantitative evaluation
      of sagittal pelvic alignment and summarize the relevant publications. STUDY
      DESIGN: Review article. METHODS: An Internet search for terms related to sagittal
      pelvic alignment was performed to obtain relevant publications, which were
      further supplemented by selected publications found in their lists of references.
      By summarizing the obtained publications, the positional and anatomic parameters
      of sagittal pelvic alignment were described, and their values and relationships
      to other parameters and features were reported. RESULTS: Positional pelvic
      parameters relate to the position and orientation of the observed subject and are
      represented by the sacral slope, pelvic tilt, pelvic overhang, sacral
      inclination, sacrofemoral angle, sacrofemoral distance, pelvic femoral angle,
      pelvic angle, and sacropelvic translation. Anatomic pelvic parameters relate to
      the anatomy of the observed subject and are represented by the pelvisacral angle
      (PSA), pelvic incidence (PI), pelvic thickness (PTH), sacropelvic angle (PRS1),
      pelvic radius (PR), femorosacral posterior angle (FSPA), sacral table angle
      (STA), and sacral anatomic orientation (SAO). The review was mainly focused on
      the evaluation of anatomic pelvic parameters, as they can be compared among
      subjects and therefore among different studies. However, ambiguous results were
      yielded for normal and pathologic subjects, as the reported values show a
      relatively high variability in terms of standard deviation for every anatomic
      parameter, which amounts to around 10 mm for PTH and PR; 10 degrees  for PSA, PI,
      and SAO; 9 degrees  for PRS1 and FSPA; and 5 degrees  for STA in the case of
      normal subjects and is usually even higher in the case of pathologic subjects.
      Among anatomic pelvic parameters, PI was the most studied and therefore
      represents a key parameter in the complex framework of sagittal spinal alignment
      and related deformities. From the reviewed studies, the regression lines for PI
      and the corresponding age of the subjects indicate that PI tends to increase with
      age for normal (PI = +0.17 * age+46.40) and scoliotic (PI = +0.20 * age+50.52)
      subjects and decrease with age for subjects with spondylolisis or
      spondylolisthesis (PI = -0.26 * age+75.69). CONCLUSIONS: Normative values for
      anatomic parameters of sagittal pelvic alignment do not exist because the
      variability of the measured values is relatively high even for normal subjects
      but can be predictive for spinal alignment and specific spinopelvic pathologies.

PMID- 22480532
TI  - The biomechanical effect of pedicle screw hubbing on pullout resistance in the
      thoracic spine.
AB  - BACKGROUND CONTEXT: The biomechanical fixation strength afforded by pedicle
      screws has been strongly correlated with bone mineral density. It has been
      postulated that "hubbing" the head of the pedicle screw against the dorsal
      laminar cortex provides a load-sharing effect, thereby limiting cephalocaudad
      toggling and improving the pullout resistance of the pedicle screw. PURPOSE: To
      evaluate the pullout strength (POS) of monoaxial hubbed pedicle screws versus
      standard fixation in the thoracic spine. STUDY DESIGN: Biomechanical
      investigation. METHODS: Twenty-two human cadaveric thoracic vertebrae were
      acquired and dual-energy X-ray absorptiometry scanned. Osteoporotic (n = 16) and
      normal (n = 6) specimens were instrumented with a 5.0 * 35-mm pedicle screw on
      one side in a standard fashion. In the contralateral pedicle, 5.0 * 30-mm screw
      was inserted with hubbing of the screw into the dorsal lamina. A difference in
      screw length was used to achieve equivalent depth of insertion. After 2,000
      cycles of cephalocaudad toggling, screws were pulled out with the tensile force
      oriented to the midline of the spine and peak POS measured in newtons (N). Four
      additional specimens were subjected to microcomputed tomography (micro-CT)
      analysis to evaluate internal pedicle architecture after screw insertion.
      RESULTS: Hubbed screws resulted in significantly lower POS (290.5 +/- 142.4 N)
      compared with standard pedicle screws (511.5 +/- 242.8 N; p = .00). This finding
      was evident in both normal and osteoporotic vertebrae based on independent
      subgroup post hoc analyses (p<.05). As a result of hubbing, half of the specimens
      fractured through the lamina or superior articular facet (SAF). No fractures
      occurred on the control side. There was no difference in mean POS for hubbed
      screws with and without fracture; however, further micro-CT analysis revealed the
      presence of internal fracture propagation for those specimens that did not have
      any external signs of failure. CONCLUSIONS: Hubbing pedicle screws results in
      significantly decreased POS compared with conventional pedicle screws. Hubbing
      predisposes toward iatrogenic fracture of the dorsal lamina, transverse process,
      or SAF during insertion.

PMID- 22480533
TI  - Isolation and partial characterization of mutants with elevated lipid content in
      Chlorella sorokiniana and Scenedesmus obliquus.
AB  - This paper describes the isolation and partial biomass characterization of high
      triacylglycerol (TAG) mutants of Chlorella sorokiniana and Scenedesmus obliquus,
      two algal species considered as potential source of biodiesel. Following UV
      mutagenesis, 2000 Chlorella and 2800 Scenedesmus colonies were screened with a
      method based on Nile Red fluorescence. Several mutants with high Nile Red
      fluorescence were selected by this high-throughput method in both species. Growth
      and biomass parameters of the strongest mutants were analyzed in detail. All of
      the four Chlorella mutants showed no significant changes in growth rate, cell
      weight, cell size, protein and chlorophyll contents on a per cell basis. Whereas
      all contained elevated total lipid and TAG content per unit of dry weight, two of
      them were also affected for starch metabolism, suggesting a change in
      biomass/storage carbohydrate composition. Two Scenedesmus mutants showed a 1.5
      and 2-fold increased cell weight and larger cells compared to the wild type,
      which led to a general increase of biomass including total lipid and TAG content
      on a per cell basis. Such mutants could subsequently be used as commercial
      oleaginous algae and serve as an alternative to conventional petrol.

PMID- 22480534
TI  - Emerging health risks associated with modern agriculture practices: a
      comprehensive study in India.
AB  - In order to enhance food production, India has adopted modern agriculture
      practices and achieved noteworthy success. This achievement was essentially the
      result of a paradigm shift in agriculture that included high inputs of
      agrochemicals, water, and widespread practice of monoculture, as well as
      bureaucratic changes that promoted these changes. There are very few
      comprehensive analyses of potential adverse health outcomes that may be related
      to these changes. The objective of this study is to identify health risks
      associated with modern agricultural practices in the southern Indian state of
      Karnataka. This study aims to compare high-input and low-input agricultural
      practices and the consequences for health of people in these communities. The
      fieldwork was conducted from May to August, 2009 and included a survey carried
      out in six villages. Data were collected by in-depth personal interviews among
      240 households and key informants, field observations, laboratory analyses, and
      data from secondary sources. The study identified four major visible impacts:
      occupational hazards, vector borne diseases, changing nutritional status, and
      inequity in development. In the high-input area, mechanization has resulted in
      more occurrences of serious accidents and injuries. Ecological changes due to
      rice cultivation in this area have further augmented mosquito breeding, and there
      has been a surge in the incidence of Japanese encephalitis and malaria. The
      traditional coarse cereals (complex carbohydrates, high protein) have been
      replaced by mill-polished rice (simple carbohydrate, low protein). The prevalence
      of overweight (BMI>25) has emerged as a new public health challenge, and this is
      most evident in large-landholding households, especially in the high-input
      agriculture areas. In all agro-ecological areas, it was observed that women faced
      a greater risk of both extremes of under-nutrition and being overweight. Output
      driven and market-oriented modern agricultural practices have changed the ecology
      and disease pattern in this area in India, and our survey indicated significant
      health effects associated with these changes. There is a need for more extensive
      epidemiological studies in order to know the full impact on diseases and to
      understand the complex causal relationships.

PMID- 22480535
TI  - Association between bone mineral density and blood lead level in menopausal
      women: analysis of 2008-2009 Korean National Health and Nutrition Examination
      Survey data.
AB  - INTRODUCTION: We present data from the Korean National Health and Nutrition
      Examination Survey 2008-2009 on the association of blood lead levels with bone
      mineral density (BMD) in menopausal women. METHODS: This cross-sectional analysis
      was restricted to female participants >= 40 years of age who completed the health
      examination survey, including blood lead measurement and BMD (n=832). Menopausal
      status was categorized into pre- and postmenopausal. Postmenopausal status was
      further categorized into natural and surgical menopause. Multivariate linear
      regression analyses were performed to determine significant predictors of blood
      lead level among menopause- and BMD-related variables after adjustment for
      covariates. RESULTS: Premenopausal women had a geometric mean blood lead level of
      2.000 MUg/dL, compared with 2.274 MUg/dL and 2.336 MUg/dL for naturally and
      surgically menopausal women, respectively. The data suggested that menopausal
      status and BMD were predictors of blood lead level among women aged >= 40 years.
      BMD was significantly inversely associated with blood lead level in menopausal
      women after adjustment for covariates. DISCUSSION: This study found a significant
      inverse association between BMD and the blood lead level in menopausal women in a
      representative sample of Korean women. A few reports have shown an association
      between BMD and the blood lead level in Asian populations. This study suggests
      that postmenopausal bone mineral resorption is related to increased blood lead
      levels in menopausal women.

PMID- 22480536
TI  - Co-occurrence of serious or undiagnosed medical conditions with bipolar disorder
      preventing clinical trial randomization: a case series.
AB  - OBJECTIVE: Studies have shown that patients with bipolar disorder have high rates
      of serious and/or untreated co-occurring general medical conditions. This case
      series examined reports of co-occurring medical conditions with bipolar disorder
      in potential clinical study participants, and in particular the percentage of
      these individuals who were previously unaware of their conditions. METHOD:
      Patients were potential participants in 1 of 2 medication trials who met DSM-IV
      criteria for bipolar disorder and were excluded from those studies just prior to
      randomization from May 2009 through July 2011. Patients were compared with each
      other on a number of demographic criteria, including age, race, gender, reason
      for exclusion from the trial, and psychiatric diagnoses. RESULTS: Of the patients
      excluded from the studies just prior to randomization, 31% (n = 10) were excluded
      because of medical conditions previously unreported by the patient during
      screening for these studies. Seventy percent of those excluded patients (n = 7)
      had no prior knowledge of their conditions. CONCLUSIONS: These results suggest
      that patients with bipolar disorder may not only have high rates of co-occurring
      medical conditions but also frequently remain unaware of those conditions. These
      findings indicate that co-occurring general medical conditions may be a more
      serious problem in the treatment of bipolar disorder than previously appreciated
      and that more stringent monitoring and guidelines are needed regardless of
      medication regimen. This case series asserts that, regardless of a patient's
      claim of having no medical conditions, more general medical screening may be
      needed in outpatient psychiatric settings.

PMID- 22480537
TI  - Successful treatment of eosinophilic esophagitis with ciclesonide.

PMID- 22480538
TI  - Relationship between red meat allergy and sensitization to gelatin and galactose
      alpha-1,3-galactose.
AB  - BACKGROUND: We have observed patients clinically allergic to red meat and meat
      derived gelatin. OBJECTIVE: We describe a prospective evaluation of the clinical
      significance of gelatin sensitization, the predictive value of a positive test
      result, and an examination of the relationship between allergic reactions to red
      meat and sensitization to gelatin and galactose-alpha-1,3-galactose (alpha-Gal).
      METHODS: Adult patients evaluated in the 1997-2011 period for suspected
      allergy/anaphylaxis to medication, insect venom, or food were skin tested with
      gelatin colloid. In vitro (ImmunoCAP) testing was undertaken where possible.
      RESULTS: Positive gelatin test results were observed in 40 of 1335 subjects: 30
      of 40 patients with red meat allergy (12 also clinically allergic to gelatin), 2
      of 2 patients with gelatin colloid-induced anaphylaxis, 4 of 172 patients with
      idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02
      0.4 g), and 4 of 368 patients with drug allergy. Test results were negative in
      all patients with venom allergy (n = 241), nonmeat food allergy (n = 222), and
      miscellaneous disorders (n = 290). ImmunoCAP results were positive to alpha-Gal
      in 20 of 24 patients with meat allergy and in 20 of 22 patients with positive
      gelatin skin test results. The results of gelatin skin testing and anti-alpha-Gal
      IgE measurements were strongly correlated (r = 0.46, P < .01). alpha-Gal was
      detected in bovine gelatin colloids at concentrations of approximately 0.44 to
      0.52 MUg/g gelatin by means of inhibition RIA. CONCLUSION: Most patients allergic
      to red meat were sensitized to gelatin, and a subset was clinically allergic to
      both. The detection of alpha-Gal in gelatin and correlation between the results
      of alpha-Gal and gelatin testing raise the possibility that alpha-Gal IgE might
      be the target of reactivity to gelatin. The pathogenic relationship between tick
      bites and sensitization to red meat, alpha-Gal, and gelatin (with or without
      clinical reactivity) remains uncertain.

PMID- 22480539
TI  - An unusual human papillomavirus type 82 detection in laryngeal squamous cell
      carcinoma: case report and review of literature.
AB  - Squamous cell carcinoma (SCC) of the larynx is extremely rare in adolescent or
      younger adult and typically has an aggressive nature. The mechanism of laryngeal
      oncogenesis is complex and little is known about the role of human
      papillomaviruses (HPVs) in SCC in young age. HPV infection may occur during birth
      or latter by oro-genital contact. Most HPV genotypes detected were HPV 6, 11, 16,
      18, 33 and 51. Herein, we report a case of invasive laryngeal SCC expressing an
      HPV 82 in an 18 year-old man with a history of unexplored severe acute dysphonia
      that started in early childhood.

PMID- 22480540
TI  - Perinatal HBV viremia in newborns of HBsAg(+) mothers is a transient phenomenon
      that does not necessarily imply HBV infection transmission.

PMID- 22480541
TI  - Niemann-Pick C1-Like 1 and cholesterol uptake.
AB  - Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein responsible
      for dietary cholesterol and biliary cholesterol absorption. Consistent with its
      functions, NPC1L1 distributes on the brush border membrane of enterocytes and the
      canalicular membrane of hepatocytes in humans. As the molecular target of
      ezetimibe, a hypocholesterolemic drug, its physiological and pathological
      significance has been recognized and intensively studied for years. Recently,
      plenty of new findings reveal the molecular mechanism of NPC1L1's role in
      cholesterol uptake, which may provide new insights on our understanding of
      cholesterol absorption. In this review, we summarized recent progress in these
      studies and proposed a working model, hoping to provide new perspectives on the
      regulation of cholesterol transport and metabolism.

PMID- 22480542
TI  - Minimally modified low-density lipoprotein induces macrophage endoplasmic
      reticulum stress via toll-like receptor 4.
AB  - Minimally modified low-density lipoprotein (mm-LDL) induces intimal foam cell
      formation, which is promoted by endoplasmic reticulum stress (ERS), a cross-point
      to link cellular processes with multiple risk factors that exist in all stages of
      atherosclerosis. However, it remains unclear whether mm-LDL-induced lipid
      accumulation in macrophages involves ERS and its underlying mechanisms. We showed
      that mm-LDL induced the accumulation of lipid droplets in RAW264.7 macrophages
      with increased free cholesterol in the endoplasmic reticulum, which was markedly
      attenuated by pretreatment with an antibody against toll-like receptor 4 (TLR4).
      Additionally, mm-LDL stimulated the transport of Cy3-labeled activating
      transcription factor 6 (ATF6), a key sensor to the unfolded protein response
      (UPR), from cytoplasm into nucleus. The expression of phosphorylated inositol
      requiring enzyme 1 (p-IRE1), another sensor to the UPR, and its two downstream
      molecules, X box binding protein 1 and glucose-regulated protein 78 (GRP78), were
      significantly upregulated by mm-LDL. The alterations induced by mm-LDL were all
      significantly inhibited by antibodies against TLR4 or CD36. In addition, the
      upregulation of p-IRE1 and GRP78 and the nuclear translocation of ATF6 induced by
      mm-LDL were significantly attenuated by TLR4 siRNA. These results suggest that mm
      LDL may induce free cholesterol accumulation in the endoplasmic reticulum and
      subsequently stimulate ERS and activate the UPR signaling pathway mediated by
      ATF6 and IRE1 in macrophages, a process that is potentially mediated by TLR4.

PMID- 22480543
TI  - Effects of methotrexate on inflammatory alterations induced by obesity: an in
      vivo and in vitro study.
AB  - Immunosuppressant drugs, such as methotrexate, are able to inhibit cytokine
      production and leukocyte migration to inflammatory foci; therefore, they could
      modify the establishment of inflammation in adipose tissue during obesity. Thus,
      we studied the effects of methotrexate in vivo on high-fat diet induced-obesity
      in mice and in vitro in isolated and co-cultured adipocytes and macrophages.
      Obese mice treated with methotrexate presented reduced serum levels of TNF-alpha,
      insulin and glucose, and an improvement of insulin sensitivity. Adipose tissue
      from these mice produced less proinflammatory (TNF-alpha, IL-6, leptin) and more
      anti-inflammatory adipokines (adiponectin and IL-10) associated with reduced
      macrophage infiltration and inflammation. Cytokine inhibition was also confirmed
      in isolated and co-cultured adipocytes and macrophages. Methotrexate presented
      anti-lipolytic effect in vivo and, in vitro through adenosine release. Drugs that
      combine anti-lipolytic effect and the ability to control inflammation in adipose
      tissue could play a role in the control of insulin resistance and other
      pathologies associated with obesity.

PMID- 22480544
TI  - Differential function of Akt1 and Akt2 in human adipocytes.
AB  - Adipose tissue mass is determined by both cell size and cell number. Mouse models
      suggest that Akt isoforms are involved in the determination of fat mass by
      interfering with preadipocyte-to-adipocyte transition and regulating lipid
      storage. Here, we took advantage of a lentiviral mediated shRNA approach to study
      the role of Akt1 and Akt2 in differentiation and metabolism of human SGBS
      adipocytes. Adipogenic differentiation as measured by lipid accumulation was
      robustly inhibited in Akt2 deficient cells, whereas it was not affected by
      knockdown of Akt1. The knockdown of Akt2 caused an almost complete inhibition of
      preadipocyte proliferation. Furthermore, Akt2 deficient preadipocytes were
      significantly more sensitive to apoptosis induction by death receptor stimulation
      compared to Akt1 deficient cells. Both the knockdown of Akt1 or Akt2 equally
      affected insulin-stimulated lipogenesis as well as the anti-lipolytic effect of
      insulin. We conclude that Akt2 is indispensable for the regulation of
      preadipocyte and adipocyte number, whereas Akt1 and Akt2 are equally important
      for the regulation of insulin-stimulated metabolic pathways in human adipocytes.
      Recently proposed as an attractive target for the treatment of cancer, modulating
      Akt2 activity might also be a new molecular strategy to control adipose tissue
      mass.

PMID- 22480545
TI  - The effects of lingual intervention in a patient with inclusion body myositis and
      Sjogren's syndrome: a longitudinal case study.
AB  - OBJECTIVE: To report the 5-year course of a patient's swallowing disorder in the
      context of progressive neuromuscular disease and the effectiveness of a lingual
      strengthening treatment program. DESIGN: This is a case report that describes a
      lingual treatment protocol that was repeated 3 times over a 5-year period with
      and without maintenance periods. SETTING: The study was completed in 2 settings
      an outpatient swallowing clinic at an acute care hospital and the patient's home.
      PARTICIPANT: The subject was a 77-year-old woman who was diagnosed with inclusion
      body myositis and Sjogren's syndrome. INTERVENTION: The patient participated in
      an intensive 8-week lingual strengthening protocol 3 times (at years 1, 4, and 5)
      and a subsequent maintenance program twice (at years 4 and 5). MAIN OUTCOME
      MEASURES: Three outcome measures were collected during the study: (1) lingual
      manometric pressures at the anterior and posterior tongue, measured by using a
      lingual manometric device, (2) airway invasion measured by using an 8-point
      Penetration-Aspiration Scale, and (3) clearance of the bolus measured by using a
      3-point residue scale. RESULTS: Isometric lingual strengthening was effective in
      maintaining posterior tongue lingual pressure and Penetration-Aspiration Scale
      scores during the treatment periods. Residue scale scores did not significantly
      change during treatment. CONCLUSIONS: We conclude that, in this patient, lingual
      strengthening slowed the progression of disease-related lingual strength loss and
      extended functional swallowing performance. Thus, this type of intervention may
      hold promise as an effective swallowing treatment option for patients with
      neurodegenerative inflammatory diseases such as inclusion body myositis and
      Sjogren's syndrome.

PMID- 22480546
TI  - Adherence to clinical guidelines improves patient outcomes in Australian audit of
      stroke rehabilitation practice.
AB  - OBJECTIVE: To study the correlation between adherence to recommended management
      and good recovery outcomes in an Australian cohort of inpatients receiving
      rehabilitation. DESIGN: Processes of care were audited and included those
      recommended in the Australian Clinical Guidelines for Stroke Rehabilitation and
      Recovery. SETTING: National audit data from 68 rehabilitation units were used,
      with each hospital contributing up to 40 consecutive cases. PARTICIPANTS: Not
      applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Discharged home
      or an increase of greater than or equal to 22 in FIM scores between admission and
      discharge. Multivariable logistic regression models controlling for patient
      clustering were used to assess the associations between adherence to recommended
      management and recovery outcomes (dependent variables). RESULTS: Hospitals
      contributed 2119 patients (median age 75y, 53% men). We found that rehabilitation
      units providing evidence-based management (eg, treatment for sensorimotor
      impairment 38%, hypertonicity 56%, mobility 94%, and home assessments 71%) were
      more likely to provide better recovery outcomes for people with stroke. A
      discharge FIM score of 100 was clinically relevant and was strongly correlated
      with whether or not a patient was discharged home. We found very good correlation
      between admission and discharge FIM scores in stroke rehabilitation. CONCLUSIONS:
      This is one of the first study comparing adherence to recommended management in
      Australian rehabilitation units and stroke recovery outcomes based on national
      audit data. Novel findings include the significance of an FIM score between 80
      and 100 and the clinical significance of various management processes.

PMID- 22480547
TI  - Reliability and validity of a low load endurance strength test for upper and
      lower extremities in patients with fibromyalgia.
AB  - OBJECTIVE: To evaluate the reliability, standard error of the mean (SEM),
      clinical significant change, and known group validity of 2 assessments of
      endurance strength to low loads in patients with fibromyalgia syndrome (FS).
      DESIGN: Cross-sectional reliability and comparative study. SETTING: University
      Pablo de Olavide, Seville, Spain. PARTICIPANTS: Middle-aged women with FS (n=95)
      and healthy women (n=64) matched for age, weight, and body mass index (BMI) were
      recruited for the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      The endurance strength to low loads tests of the upper and lower extremities and
      anthropometric measures (BMI) were used for the evaluations. The differences
      between the readings (tests 1 and 2) and the SDs of the differences, intraclass
      correlation coefficient (ICC) model (2,1), 95% confidence interval for the ICC,
      coefficient of repeatability, intrapatient SD, SEM, Wilcoxon signed-rank test,
      and Bland-Altman plots were used to examine reliability. A Mann-Whitney U test
      was used to analyze the differences in test values between the patient group and
      the control group. We hypothesized that patients with FS would have an endurance
      strength to low loads performance in lower and upper extremities at least twice
      as low as that of the healthy controls. RESULTS: Satisfactory test-retest
      reliability and SEMs were found for the lower extremity, dominant arm, and
      nondominant arm tests (ICC=.973-.979; P<.001; SEMs=1.44-1.66 repetitions). The
      differences in the mean between the test and retest were lower than the SEM for
      all performed tests, varying from -.10 to .29 repetitions. No significant
      differences were found between the test and retest (P>.05 for all). The Bland
      Altman plots showed 95% limits of agreement for the lower extremity (4.7 to 
      4.5), dominant arm (3.8 to -4.4), and nondominant arm (3.9 to -4.1) tests. The
      endurance strength to low loads test scores for the patients with FS were 4-fold
      lower than for the controls in all performed tests (P<.001 for all). CONCLUSIONS:
      The endurance strength to low loads tests showed good reliability and known group
      validity and can be recommended for evaluating endurance strength to low loads in
      patients with FS. For individual evaluation, however, an improved score of at
      least 4 and 5 repetitions for the upper and lower extremities, respectively, was
      required for the differences to be considered as substantial clinical change.
      Patients with FS showed impaired endurance strength to low loads performance when
      compared with the general population.

PMID- 22480548
TI  - Determinants of limb preference for initiating compensatory stepping poststroke.
AB  - OBJECTIVE: To investigate the determinants of limb preference for initiating
      compensatory stepping poststroke. DESIGN: Retrospective chart review. SETTING:
      Inpatient rehabilitation. PARTICIPANTS: Convenience sample of individuals
      admitted to inpatient rehabilitation with poststroke hemiparesis. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Compensatory stepping responses were
      evoked using a lean-and-release postural perturbation. The limb used to initiate
      compensatory stepping was determined. The relationships between stepping with the
      paretic limb and premorbid limb dominance, weight bearing on the paretic limb in
      quiet standing, ability to bear weight on the paretic limb, preperturbation
      weight bearing on the paretic limb, and lower-limb motor recovery scores were
      determined. RESULTS: The majority (59.1%) of responses were steps initiated with
      the nonparetic limb. Increased lower-limb motor recovery scores and
      preperturbation weight bearing on the nonparetic limb were significantly related
      to increased frequency of stepping with the paretic limb. When the preferred limb
      was physically blocked, an inappropriate response was initiated in 21% of trials
      (ie, nonstep responses or an attempt to step with the blocked limb). CONCLUSIONS:
      This study reveals the challenges that individuals with poststroke hemiparesis
      face when executing compensatory stepping responses to prevent a fall after a
      postural perturbation. The inability or challenges to executing a compensatory
      step with the paretic limb may increase the risk for falls poststroke.

PMID- 22480549
TI  - Co-occurring traumatic brain injury and acute spinal cord injury rehabilitation
      outcomes.
AB  - OBJECTIVE: To determine the impact of co-occurring traumatic brain injury (TBI)
      on functional motor outcome and cognition during acute spinal cord injury (SCI)
      rehabilitation. DESIGN: Prospective, longitudinal cohort. SETTING: Single-center
      National Institute of Disability and Rehabilitation Research SCI Model System.
      PARTICIPANTS: Persons aged 16 to 59 years (N=189) admitted for acute SCI
      rehabilitation during the 18-month recruitment window who met inclusion criteria.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FIM Motor Scale (Rasch
      transformed) and acute rehabilitation length of stay (LOS). RESULTS: In the
      tetraplegia sample, co-occurring TBI was not related to FIM Motor Scale scores or
      acute rehabilitation LOS despite having negative impacts on memory and problem
      solving. Persons with paraplegia who sustained co-occurring severe TBI had lower
      admission and discharge FIM Motor Scale scores and longer acute rehabilitation
      LOS than did persons with paraplegia and either no TBI or mild TBI. Persons with
      paraplegia and severe TBI had lower functional comprehension, problem solving,
      and memory and impairments on tests of processing speed compared with persons
      with paraplegia and no TBI, mild TBI, and moderate TBI. Persons with paraplegia
      and co-occurring mild and moderate TBI had equivalent acute rehabilitation motor
      outcomes and cognitive functioning compared with persons with paraplegia and no
      TBI. CONCLUSIONS: This study provides evidence that persons aged 16 to 59 years
      with paraplegia and co-occurring severe TBI had worse motor outcomes and longer
      acute rehabilitation LOS than did persons with paraplegia and no TBI. Impairments
      in processing speed, comprehension, memory, and problem solving may explain
      suboptimal motor skill acquisition. Research with larger samples is required to
      determine whether mild and moderate TBI impact acute rehabilitation motor
      outcomes and LOS.

PMID- 22480550
TI  - [Anaesthesia in rare diseases].

PMID- 22480551
TI  - [Assessment of learning in blind orotracheal intubation with Fastrach masks using
      a cumulative sum curves (CuSum) in the SimMan Universal Simulator].
AB  - OBJECTIVE: To assess training in blind intubation with the Fastrach laryngeal
      mask in a simulation model by applying the cumulative sums (CuSum) method.
      MATERIAL AND METHODS: Six anaesthesiology resident doctors, with no previous
      experience of the technique, participated, three in their first year, and three
      in the second. The study was conducted with the help of the SimMan Universal
      Simulator. Fifty attempts by each one of them over a four month period, divided
      into two stages: the first 20 with minimum airway difficulty, and the next 30
      with limitations of flexion-extension movements to <80 degrees . An unacceptable
      failure rate was set at 10% after a second failed attempt. The time limit set to
      be considered a success was 60seconds. RESULTS: A total of 120 attempts in the
      first stages, and the remaining 180 in the second were analysed individually, all
      managing to achieve acceptable success rates of 90%: 84% in the first attempt and
      13.33% in the second. A total of 2.66% failures were recorded. The learning curve
      showed that the residents began to achieve an acceptable 90% success rate in case
      number 25+/-11.76 of the 50 attempts. CONCLUSIONS: This statistical method and
      the SimMan simulator, used together, have demonstrated to be very useful tools in
      assessing learning curves in this technique.

PMID- 22480552
TI  - [Blind tracheal intubation through two supraglottic devices: i-gel versus
      Fastrach intubating laryngeal mask airway (ILMA)].
AB  - BACKGROUND AND OBJECTIVES: The use of supraglottic devices as a means of rescue
      in patients difficult to intubate or ventilate has increased in the field of
      anaesthetics and in emergency medicine. This study is designed to evaluate the
      success rate of blind intubations using two supraglottic devices, the Fastrach
      ILMA and the i-gel mask. PATIENTS AND METHODS: A total of 80 patients (40 per
      group) were included. After positioning them a leak test was performed, the
      glottis view was checked with a fibrobronchoscope, and an attempt was made to
      introduce an endotracheal tube through the device, and the procedure was
      repeated. Adequate ventilation was evaluated, as well as the grade of
      fibrobronchoscope view, the success of the intubation, and the complications
      observed after their use. RESULTS: There were no differences in the incidence of
      adequate ventilation with either device. The glottis view (Brimacombe scale) was
      better with i-gel (77.78% versus 68.42%) at the second attempt, but not on the
      first. A higher percentage of intubations were achieved with the Fastrach ILMA
      (70% versus 40%; P=.013). The incidence of throat pain was similar with both
      devices, but post-operative dysphonia was more frequent with i-gel (20% versus 0;
      P=.0053). CONCLUSIONS: Both devices were equally effective in achieving adequate
      ventilation; however, the Fastrach ILMA enabled a higher number of intubations to
      be made than i-gel and with a lower incidence of post-operative dysphonia.

PMID- 22480553
TI  - [Analysis of the causes for increases in the length of stay in the Recovery Unit
      of La Paz Maternity Hospital in 2008].
AB  - OBJECTIVE: To establish the spectrum of diseases in the obstetric patient that
      involves an increase in the length of stay in the Recovery Unit of a specialist
      Maternity Hospital. To analyse the severity of these conditions as regards the
      means required for their resolu-tion, as well as to identify the factors that
      influence on post-operative morbidity in the obstetric patient. MATERIAL AND
      METHODS: All the case histories of all the patients admitted to the Maternity
      Hospital Recovery Unit during the year 2008 were reviewed. Those who required a
      lon-ger stay than usual were selected, which included, those with more than
      6hours after a caesarean, and all admissions made during pregnancy, or after
      dilation and curettage or partum. RESULTS: Out of a total of 10419 births
      delivered in 2008, 3000 obstetric patients were ad-mitted to the Maternity
      Hospital Recovery Unit, of which 285 (9.5%) required critical care. The most
      frequent cause of increased length of stay was obstetric haemorrhage, followed by
      hypertensive states of pregnancy. No patients died in this Unit in the year 2008.
      CONCLUSIONS: The number of patients who had an increased length of stay in the
      Mater-nity Hospital Recovery Unit is similar to the percentage of patients who
      are admitted to Intensive Care Units in countries such as Canada or the United
      Kingdom, but our Unit had a lower death rate in the year evaluated. The main
      causes are obstetric haemorrhage and hypertensive states of pregnancy, thus
      patients with risk factors for developing these complications must be observed
      closely and monitored.

PMID- 22480554
TI  - [Parental anxiety increases pre-operative anxiety in the paediatric patient
      subjected to day surgery].
AB  - OBJECTIVE: To evaluate the pre-operative anxiety associated with parental anxiety
      in children subjected to day surgery, by studying the parent-child behaviour and
      interaction in the surgical environment. MATERIAL AND METHODS: A prospective,
      observational and cross-sectional study was conducted on 98 paediatric patients,
      between 2 and 10 years-old, scheduled for elective day surgery with general
      anaesthesia. The modified YALE Pre-operative Anxiety Scale was applied, and the
      parents were independently evaluated using the Hamilton Anxiety Test. RESULTS:
      Pre-operative anxiety was present in 71.4% of the patients. Children between 5
      and 7 years had a significantly higher risk of presenting with anxiety (P=.05).
      In the parents group, 55.2% showed mild anxiety, and 9.2% moderate. The mother
      was the family member who most often accompanied the paediatric patient.
      CONCLUSIONS: The anxiety in children subjected to surgery is characterised by
      subjective feelings of tension, fear, nervousness, and worry that could be
      expressed in diverse forms. The evaluation of anxiety in the pre-operative period
      is an excellent tool to start and to perform both psychological and
      pharmacological interventions.

PMID- 22480555
TI  - [Update on the use of uterotonic agents].
AB  - Postpartum haemorrhage (PPH) is defined by the WHO as a blood loss >500mL after
      vaginal delivery or >1000mL after caesarean section during the first 24hours post
      delivery. Although the incidence of maternal mortality caused by PPH has
      decreased, it continues to be the major cause of maternal mortality due to
      obstetric haemorrhage. Furthermore, the incidence of uterine atony, which is the
      most prevalent cause of PPH, is still increasing in both vaginal delivery and
      caesarean section. Although PPH occurs in more than two thirds of patients
      without any identifiable risk factor, a prolonged third stage of labour is the
      main risk factor. Active management of the third stage of labour has been
      postulated to reduce the risk of bleeding in this period. It includes the
      administration of uterotonic agents after the birth of the baby. Uterotonic
      agents are defined as drugs that produce adequate uterine contraction. These
      drugs can be used as prophylactic therapy or treatment. The prophylactic use of
      uterotonic agents has been reported to be associated with a shorter third stage
      of labour, less risk of PPH and less need of additional uterotonic agents. There
      are currently four drugs or groups of drugs with uterotonic action: oxytocin,
      carbetocin, ergot derivatives and prostaglandins. The literature on this subject
      is extensive, heterogeneous and sometimes discordant. Oxytocin is still the first
      line uterotonic drug for prophylaxis and treatment of uterine atony. There is a
      common trend to use high doses of uterotonics for fear of inadequate uterine
      contraction, but the current literature recommends its reduction.
      Methylergonovine continues being the second-line uterotonic agent in the
      prophylaxis and treatment of PPH, because of its side effects. Despite carboprost
      (PGF2alpha) side effects, it is still the first-line prostaglandin for PPH
      treatment. Misoprostol may be an alternative to oxytocin when it is not
      available, although it needs further studies to support this. Finally, the
      prophylactic use of carbetocin should be individualised.

PMID- 22480556
TI  - [Conradi-Hunermann Chondrodysplasia punctata: anaesthetic implications].
AB  - Chondrodysplasia punctata syndrome is a group of rare congenital diseases that
      give rise to malformations, mainly skeletal, linked to the premature
      calcification of structures. There is little in the literature in the field of
      Anaesthesiology on this despite there being some clinical manifestations,
      particularly the possibility of difficult airway, which may be of importance
      during the peri-operative period. During the first years of life, the patients
      affected are often subjected to repeated surgery to correct their malformations.
      We describe the anaesthetic treatment during orthopaedic surgery of a paediatric
      patient with Conradi-Hunermann type chondrodysplasia punctata, highlighting the
      managementof the airway using a laryngeal mask in combination with balanced
      general anaesthesia with remifentanil. We also present a review of the
      characteristics of the different entities of these syndromes, with special
      emphasis on the aspects most relevant to the anaesthesiologist.

PMID- 22480557
TI  - Anesthetic management of a patient diagnosed with CADASIL (cerebral arteriopathy,
      autosomal dominant, with subcortical infarcts and leukoencephalopathy).
AB  - CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and
      leu-koencephalopathy) is an infrequent inherited disease that could have
      anesthetic implica-tions. However these have rarely been reported. We present a
      male patient previously diagnosed with CADASIL, who had suffered an ischemic
      vascular cerebral accident with a MRI compatible with leukoencephalopathy, and
      who was dependent for daily activities, and sustained dementia, mood alterations,
      apathy, and urine incontinence. He had famil-ial antecedents of psychiatric
      symptoms and ischemic stroke events in several relatives including his father,
      two brothers and one sister. He was scheduled for arthrodesis of the left knee
      because of multiple infectious complications of prosthetic knee surgery. He was
      under clopidogrel treatment which was withdrawn seven days before surgery. The
      pro-cedure was performed under combined spinal-epidural anesthesia,
      intraoperative seda-tion with midazolam, and postoperative multimodal analgesia
      including epidural patient controlled analgesia. The perioperative management was
      uneventful and we outline the adequacy of managing these patients under regional
      anesthesia and analgesia, as these permit to maintain hemodynamic stability
      leading to adequate cerebral perfusion, key to avoid an increase in the effects
      of the chronic arteriopathy patients with CADASIL sustain.

PMID- 22480558
TI  - [General anaesthesia in a patient with Clarkson syndrome].

PMID- 22480559
TI  - [General anaesthesia combined with epidural analgesia for ureteroneocystostomy in
      a patient with Cornelia de Lange syndrome].

PMID- 22480560
TI  - [Anaesthetic implications of Gorham syndrome].

PMID- 22480561
TI  - [Management of anaesthesia and the airway in a child with Goldenhar syndrome].

PMID- 22480562
TI  - [Non-viable neonatal gastroschisis].

PMID- 22480563
TI  - Rethinking Evaluations of Health Equity Initiatives: an introduction to the
      special issue.
AB  - This paper is an introduction to a special issue on "Re-thinking Evaluations of
      Health Equity Initiatives." The papers in this volume aim to build understanding
      of how evaluations can contribute to addressing inequities and how evaluation
      design can develop a better understanding and also better respond to: (i) policy
      maker and practitioner needs; (ii) the systemic and complex nature of the
      interventions necessary to impact inequities; (iii) an understanding of the
      processes that generate inequities.

PMID- 22480564
TI  - Using logic models to facilitate comparisons of evaluation theory.

PMID- 22480565
TI  - Getting real about policy and practice needs: evaluation as a bridge between the
      problem and solution space.
AB  - This paper introduces the concept of problem and solution spaces, its relevance
      to planning and evaluating health equity interventions and how evaluations can
      serve as a bridge between problem and solution spaces. A number of questions are
      described as part of evaluative thinking about solutions that can help with
      planning more rigorous and context sensitive solutions to health inequities. The
      questions are informed by conceptual, operational and strategic issues that need
      to be addressed in evaluating health inequities.

PMID- 22480566
TI  - Bis(methyl)gliotoxin proves to be a more stable and reliable marker for invasive
      aspergillosis than gliotoxin and suitable for use in diagnosis.
AB  - The virulence factor gliotoxin (GT) and its inactive derivative,
      bis(methylthio)gliotoxin (bmGT), are produced by pathogens of the genus
      Aspergillus. Here we report the detection of GT and bmGT in serum of humans at
      risk of invasive aspergillosis (IA) as well as in cultures of fungal isolates
      derived from patients with proven infection with A. fumigatus. Although both
      compounds are readily recoverable from spiked human serum or plasma, only bmGT is
      retained in whole blood, indicating that bmGT may be the better marker for in
      vivo detection. Accordingly, bmGT was found more frequently than GT in samples
      from patients at risk of IA and incultures of clinical isolates of A. fumigatus.
      In some cases, bmGT was detected before mycologic evidence ofinfection was
      gained. Importantly, neither GT nor bmGT was found in serum from healthy donors
      or from neutropenic patients without any sign of infection. Thus, bmGT presence
      might provide a more reliable indicator of A. fumigatus infections than GT. Due
      to its simplicity and sensitivity, a diagnostic technology based on this test
      could be easily adopted in clinical laboratories to help in the diagnosis of this
      often fatal fungal infection.

PMID- 22480567
TI  - Evaluation of the BD MAX GBS assay to detect Streptococcus group B in LIM broth
      enriched antepartum vaginal-rectal specimens.
AB  - The BD MAX GBS real-time polymerase chain reaction assay was evaluated
      concomitantly with Centers for Disease Control and Prevention-endorsed culture
      methods to detect Streptococcus group B from LIM broth-enriched antepartum
      vaginal-rectal specimens. The sensitivity of both methods exceeded 98%.

PMID- 22480568
TI  - Evaluation of disk diffusion method compared to broth microdilution for
      antifungal susceptibility testing of 3 echinocandins against Aspergillus spp.
AB  - We tested the susceptibility of caspofungin, micafungin, and anidulafungin
      against Aspergillus spp. isolates by the new Clinical and Laboratory Standards
      Institute M51-A disk diffusion (DD) and the broth microdilution methods. A total
      of 65 clinical isolates of Aspergillus spp. were evaluated. The DD assay was
      performed on nonsupplemented Mueller-Hinton agar using caspofungin 2-MUg,
      micafungin 1-MUg, and anidulafungin 2-MUg disks. Echinocandin minimal effective
      concentrations (MECs) and inhibition zones (IZs) were read after 24 to 48 (A.
      terreus) h at 35  degrees C. Caspofungin MECs for all Aspergillus spp. strains
      tested were <= 0.25 MUg/mL; IZs were >= 15 mm for most species except for A.
      terreus (11-22 mm). Both micafungin and anidulafungin MECs were <= 0.015 MUg/mL,
      but micafungin IZs were >= 14 mm while anidulafungin IZs were >= 22 mm. As for
      caspofungin, the DD method could be a useful method for susceptibility testing of
      micafungin and anidulafungin against Aspergillus spp.

PMID- 22480571
TI  - Pathology of extra-nodal non Hodgkin lymphomas.
AB  - In the management of extra-nodal lymphomas it is important to determine whether
      the tumour has disseminated and whether lymph nodes are involved. Some extra
      nodal lymphomas may be the result of random spread of nodal lymphoma. Specific
      homing, however, determines the site of many extra-nodal lymphomas, as
      exemplified by cutaneous T-cell lymphomas, which seem to be derived from skin
      homing T-cells and mucosa-associated lymphoid tissue lymphomas that show features
      of the mucosal immune system. Enteropathy-associated T-cell lymphoma is derived
      from mucosal T-cells in patients with coeliac disease. Immunological sanctuary
      accounts for the localisation of primary brain, eye and testicular lymphoma.
      Mantle cell lymphoma frequently causes tumours in the gastrointestinal tract.
      Random biopsies have shown that a high proportion of patients with this lymphoma
      have extensive occult involvement of the gastrointestinal tract at the time of
      first diagnosis. Follicular lymphoma occurs at both nodal and extra-nodal sites,
      but uncommonly at both sites at the same time. Extra-nodal follicular lymphomas
      frequently lack t(14;18)(q32;q21) and do not express bcl-2, which are
      characteristics of the nodal disease. At extra-nodal sites, follicular lymphoma
      is more likely to be curable than nodal follicular lymphoma. The behaviour of
      extra-nodal lymphomas cannot be assumed to follow that of their nodal
      counterparts.

PMID- 22480572
TI  - Skin lymphoma.
AB  - Lymphoma arising from the skin is the second most common site of extra-nodal non
      Hodgkin's lymphoma. Over the last 25 years, the incidence has been rising. There
      is now a new World Health Organization/European Organization for Research and
      Treatment of Cancer joint classification for cutaneous lymphomas and new proposed
      International Society for Cutaneous Lymphomas/European Organization for Research
      and Treatment of Cancer staging systems. This overview examines the role of
      radiotherapy in the current management of cutaneous T- and B-cell lymphomas
      encompassing technological advances, new systemic therapies and novel radio
      enhancing therapies now available. Modern total skin electron beam radiotherapy
      and the current low-dose and combination approaches are reviewed. Radiotherapy
      has remained the most successful treatment for cutaneous lymphoma over the last
      50 years and with the technological advances and combination approaches available
      now and in the future will remain so for the next 50 years.

PMID- 22480574
TI  - Electrospray-differential mobility analysis of bionanoparticles.
AB  - Electrospray-differential mobility analysis (ES-DMA) is a versatile technique
      used to aerosolize bionanoparticles and measure their electrical mobility at
      ambient conditions. ES-DMA is similar to electrospray-mass spectrometry (ES-MS),
      but measures the effective particle size, rather than mass. It has a wide range
      of applications and nominally can be used to characterize biomolecules and
      nanoparticles ranging in size from a few nanometers (~3 nm) to several hundred
      nanometers, to obtain multimodal size distributions in minutes. Although both the
      ES and the DMA are mature technologies, they are finding increased use in
      combination to characterize particles in liquids. In this paper, we review ES
      DMA, and how it has recently been used to characterize bionanoparticles such as
      polymers, proteins, viruses, bacteriophages and nanoparticle-biomolecule
      conjugates.

PMID- 22480575
TI  - Grapevine deformation virus: completion of the sequence and evidence on its
      origin from recombination events between Grapevine fanleaf virus and Arabis
      mosaic virus.
AB  - The complete nucleotide (nt) sequence of Grapevine deformation virus (GDefV) RNA
      1 has been determined. It consists of 7386 nt, excluding the poly(A) tail, and
      contains a single open reading frame (ORF) encoding a polyprotein (p1) of 252
      kDa. P1 comprises the 1A(Pro-cof) proteinase cofactor, the 1B(Hel) NTP-binding
      protein, the 1C(VPg) viral protein genome-linked, the 1D(Prot) proteinase and the
      1E(Pol) RNA-dependent RNA polymerase, all of which are conserved domains in
      polyproteins of different members of the order Picornavirales. The amino acid
      (aa) sequence of GDefV RNA1 p1 has the highest identity with the homologous
      products of Grapevine fanleaf virus (GFLV, 86-88%) and Arabis mosaic virus (ArMV,
      73-74%), two nepoviruses of subgroup A. Four cleavage sites for proteins
      processing were predicted (C/A, C/S, G/E and R/G) and found similar to those of
      GFLV RNA1. Phylogenetic trees constructed with the complete aa sequences of
      protein p1 and the RNA2-encoded protein p2 of GDeFV, GFLV and ArMV, showed an
      incongruent allocation of GDefV in these trees. Pairwise alignment and prediction
      of recombination sites of both RNA segments showed that GDefV RNA2 has a mosaic
      structure resulting from recombination events between GFLV and ArMV at the level
      of the 2A(HP) (homing protein), 2B(MP) (movement protein), 2C(CP) (capsid
      protein) and the 3'NCR (non coding region). This strongly suggests that GDefV
      originated from the interspecific recombination between isolates of GFLV and
      ArMV.

PMID- 22480576
TI  - Isolation and characterization of CD133+CD34+VEGFR-2+CD45- fetal endothelial
      cells from human term placenta.
AB  - The phenotypes and functions of endothelial cells (EC), a heterogeneous cell
      population, vary along the vascular tree and even in the same organ between
      different vessels. The placenta is an organ with abundant vessels. To enhance
      further knowledge concerning placenta derived EC, we develop a new method for
      isolation, purification and culture of these EC. Moreover, in order to
      investigate the peculiarity of placenta derived EC we compare their phenotypic
      and functional characteristics with human dermal lymphatic endothelial cells
      (HDLEC) and human umbilical vein endothelial cells (HUVEC). Freshly isolated
      placenta derived EC displayed an elongated shape with pale cytoplasm and showed
      the typical cobblestone pattern of EC but also a swirling pattern when confluent.
      FISH-analyses of the isolated EC from placentae of male fetus revealed an XY
      genotype strongly indicating their fetal origin. Characterisation of placenta
      derived fetal EC (fEC) underlined their blood vessel phenotype by the expression
      of vWF, Ulex europaeus lectin-1, HLA-class I molecules, CD31, CD34, CD36,
      CD51/61, CD54, CD62E, CD105, CD106, CD133, CD141, CD143, CD144, CD146, VEGFR-1,
      VEGFR-2, EN-4, PAL-E, BMA120, Tie-1, Tie-2 and alpha-Tubulin. In contrast to
      previous reports the expression of lymphatic markers, like VEGFR-3, LYVE-1, Prox
      1 and Podoplanin was consistently negative. Haematopoietic surface markers like
      CD45 and CD14 were also always negative. Various functional tests (Dil-Ac-LDL
      uptake, Matrigel assay and TNF-alpha induced upregulation of CD62E and CD54)
      substantiated the endothelial nature of propagated fEC. At the ultrastructural
      level, fEC harboured numerous microvilli, micropinocytic vesicles at their basis,
      were rich in intermediate filaments and possessed typical Weibel - Palade bodies.
      In conclusion, the placenta is a plentiful source of fetal, microvascular, blood
      EC with an expression profile (CD34+, CD133+, VEGFR-2+, CD45-) suggestive of an
      endothelial progenitor phenotype.

PMID- 22480577
TI  - A risk, injury, failure, loss, and end-stage renal failure score-based trigger
      for renal replacement therapy and survival after cardiac surgery.
AB  - PURPOSE: It is controversial whether all critically ill patients with risk,
      injury, failure, loss, and end-stage renal failure (RIFLE) F class acute kidney
      injury (AKI) should receive renal replacement therapy (RRT). We reviewed the
      outcome of open heart surgery patients with severe RIFLE-F AKI who did not
      receive RRT. MATERIALS AND METHODS: We identified all patients with AKI after
      cardiac surgery over 4 years and obtained baseline characteristics,
      intraoperative details, and in-hospital outcomes. We analyzed physiologic and
      biochemical features at RRT initiation or at peak creatinine if no RRT was
      provided. RESULTS: We reviewed 1504 patients. Of these, 137 (9.1%) developed
      postoperative AKI with 71 meeting RIFLE-F criteria and 23 (32.4% of RIFLE-F
      cases) not receiving RRT. Compared with RRT-treated RIFLE-F patients, "no-RRT"
      patients had lower Acute Physiology and Chronic Health Evaluation III scores,
      less intra-aortic balloon pump requirements, shorter intensive care stay, and a
      trend toward lower mortality. At peak RIFLE score, their urinary output, arterial
      pH, and Pao(2)/fraction of inspired oxygen ratio were all significantly higher.
      Their serum creatinine was also higher (304 vs 262 MUmol/L; P = .02). Only 3
      RIFLE-F no-RRT patients died in-hospital. Detailed review of cause and mode of
      death was consistent with non-RRT-preventable deaths. In contrast, 27 patients
      with RIFLE-R or RIFLE-I class received RRT. Compared with RRT-treated RIFLE-F
      patients, such RIFLE-R or RIFLE-I treated patients had a more severe presentation
      and higher mortality (51.8% vs 29.2%; P = .02). CONCLUSIONS: After cardiac
      surgery, RRT was typically applied to patients with the most severe clinical
      presentation irrespective of creatinine levels. A RIFLE score-based trigger for
      RRT is unlikely to improve patient survival.

PMID- 22480578
TI  - 3,5-Di-t-butyl catechol is a potent human ryanodine receptor 1 activator, not
      suitable for the diagnosis of malignant hyperthermia susceptibility.
AB  - 3,5-Di-t-butyl catechol (DTCAT) releases Ca(2+) from rat skeletal muscle
      sarcoplasmic reticulum (SR) vesicles. Hence, it is a candidate for use as a
      substitute for halothane or caffeine in the in vitro contracture test for the
      diagnosis of susceptibility to malignant hyperthermia (MH). To characterize the
      effect of DTCAT at cell level, Ca(2+) release experiments were performed on
      cultured, human skeletal muscle myotubes using the fluorescent Ca(2+) indicator
      fura2-AM. DTCAT was also assayed in the in vitro contracture test on human
      skeletal muscle bundles obtained from individuals diagnosed susceptible (MHS),
      normal (MHN) or equivocal for halothane (MHEH) and compared to the standard test
      substances caffeine and halothane. DTCAT increased, in a concentration-dependent
      manner and with a higher efficacy as compared to caffeine, the free,
      intracellular Ca(2+) levels of cultured MHN and MHS skeletal muscle myotubes.
      This effect was similar in both types of myotubes and involved the release of
      Ca(2+) from SR stores as well as Ca(2+)-influx from the extracellular space.
      Inhibition of ryanodine receptors either with ryanodine or with ruthenium red
      markedly reduced DTCAT-induced increase in intracellular Ca(2+) concentration
      while abolishing that induced by caffeine. In MHN skeletal muscle bundles, DTCAT
      induced contractures with an EC(50) value of 160 +/- 91 MUM. However, the
      sensitivity of MHS or MHEH muscles to DTCAT was similar to that of MHN muscles.
      In conclusion, DTCAT is not suitable for the diagnosis of MH susceptibility due
      to its failure to discriminate between MHN and MHS muscles.

PMID- 22480580
TI  - Can pyrene be localized inside lipid bilayers by simultaneously measuring Py
      values, and fulfilling the excimer formation conditions?

PMID- 22480579
TI  - Acentrosomal spindle assembly and chromosome segregation during oocyte meiosis.
AB  - The ability to reproduce relies in most eukaryotes on specialized cells called
      gametes. Gametes are formed by the process of meiosis in which, after a single
      round of replication, two successive cell divisions reduce the ploidy of the
      genome. Fusion of gametes at fertilization reconstitutes diploidy. In most animal
      species, chromosome segregation during female meiosis occurs on spindles
      assembled in the absence of the major microtubule-organizing center, the
      centrosome. In mammals, oocyte meiosis is error prone and underlies most birth
      aneuploidies. Here, we review recent work on acentrosomal spindle formation and
      chromosome alignment/separation during oocyte meiosis in different animal models.

PMID- 22480581
TI  - Argumentation logic for the flexible enactment of goal-based medical guidelines.
AB  - RESEARCH PURPOSE: We have designed a prototype clinical workflow system that
      allows the specification and enactment of medical guidelines in terms of clinical
      goals to be achieved, maintained or avoided depending on the patient's disease
      and treatment evolution. The prototype includes: (1) an argumentation-based
      decision support system which can be used both to represent medical decisions
      within guidelines, and to dynamically choose the most suitable plans to achieve
      clinical goals, and (2) mechanisms to specify a health organization's facilities
      and health workers skills and roles, which can be taken into account during the
      decision process in order to improve quality of care. RESULTS: The framework has
      been fully implemented in the COGENT formal modeling system. The prototype has
      been evaluated implementing a hypertension guideline. CONCLUSIONS: The framework
      has shown flexibility and adaptability in (1) advising and tailoring health care
      based on a health organization's resources and a patient's particular medical
      condition, (2) delegating health care, and (3) replanning when unexpected
      situations arise.

PMID- 22480582
TI  - Multiple ant colony algorithm method for selecting tag SNPs.
AB  - The search for the association between complex disease and single nucleotide
      polymorphisms (SNPs) or haplotypes has recently received great attention. Finding
      a set of tag SNPs for haplotyping in a great number of samples is an important
      step to reduce cost for association study. Therefore, it is essential to select
      tag SNPs with more efficient algorithms. In this paper, we model problem of
      selection tag SNPs by MINIMUM TEST SET and use multiple ant colony algorithm
      (MACA) to search a smaller set of tag SNPs for haplotyping. The various
      experimental results on various datasets show that the running time of our method
      is less than GTagger and MLR. And MACA can find the most representative SNPs for
      haplotyping, so that MACA is more stable and the number of tag SNPs is also
      smaller than other evolutionary methods (like GTagger and NSGA-II). Our software
      is available upon request to the corresponding author.

PMID- 22480583
TI  - And now for something completely different . . . Self-management.

PMID- 22480584
TI  - Supported self-management: a simple, effective way to improve depression care.
AB  - OBJECTIVES: To introduce supported self-management (SSM) for depression, examine
      it through the use of a quality assessment framework, and show its potential for
      enhancing the Canadian health care system. METHOD: SSM is examined in terms of
      quality criteria: relevance, effectiveness, appropriateness, efficiency, safety,
      acceptability, and sustainability. Critical research is highlighted, and a case
      study is presented to illustrate the use of SSM with depressed patients. RESULTS:
      SSM is defined by access to a self-management guide (workbook or website) plus
      encouragement and coaching by health care provider, family member, or other
      supporter. It has high relevance to depression care in Canada, high cost
      effectiveness, high appropriateness for most people with depression, and high
      safety. Acceptability of this intervention is more problematic: many providers
      remain doubtful of its acceptability to their poorly motivated patients.
      Sustainability of SSM as a component of mental health care will require ongoing
      knowledge exchange among policy-makers, health care providers, and researchers.
      CONCLUSION: The introduction of SSM represents a unique opportunity to enhance
      the delivery of depression care in Canada. Actively engaging the distressed
      individual in changing depressive patterns can improve outcomes without
      mobilizing substantial new resources. Over time, we will learn more about making
      SSM compatible with constraints on provider time, increasing access to self
      management tools, and evaluating the benefit to everyday clinical work.

PMID- 22480585
TI  - Stepped care: a method to deliver increased access to psychological therapies.
AB  - OBJECTIVE: To introduce stepped care as a method of organizing the delivery of
      treatments, and to consider the factors necessary for implementation. METHOD:
      Stepped care is described within the context of strategies such as collaborative
      care that aim to increase access to mental health care through the improved
      coordination of care between primary and specialist mental health services.
      Results from the implementation of stepped care in the United Kingdom and
      elsewhere are used to highlight the factors required for introducing stepped care
      into routine services. Issues to address when implementing high-volume services
      for common mental health problems are derived from this experience. RESULTS:
      Stepped care sits within the continuum of organizational systems, from situations
      where responsibility rests almost entirely with primary care clinicians to
      systems where all patients are managed by specialists for the entire duration of
      their treatment. Its core principles of delivering low-burden treatments first,
      followed by careful patient progress monitoring to step patients up to more
      intensive treatment, are easy to articulate but lead to considerable
      implementation diversity when services attempt to work in this manner. Services
      need to ensure they have specific staff competency training, including skills in
      delivering evidence-based treatments, access to telephony, and smart patient
      management informatics systems. CONCLUSIONS: Stepped care can provide the
      delivery system for supported self-management. To be successful, health systems
      need high levels of clinical outcome data and appropriately trained workers.
      Further attention is required to ensure equity of access and to reduce patient
      attrition in these systems.

PMID- 22480586
TI  - Clinical course and personality in reactive, compared with nonreactive,
      delusional disorder.
AB  - OBJECTIVE: Reactive delusional disorder (DD) (with a precipitating factor) has
      been postulated to differ clinically from nonreactive DD and to show a better
      prognosis. Our study tests this hypothesis in a sample of patients with
      persistent DD (International Classification of Diseases, 10th Revision) or DD
      (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) followed
      during a period of more than 10 years. METHOD: As part of a long-term study on
      DD, 19 patients with DD and a stressful life event preceding the onset of the
      disorder were compared with 24 DD patients without such a life event. Diagnoses,
      social and biographical data, life events, and outcome were assessed by a
      semistructured interview and validated rating scales. Personality features were
      assessed by the NEO Five-Factor Inventory and by the Inventory of Clinical
      Personality Accentuations. RESULTS: Patients with reactive DD tended to be
      somewhat younger but showed otherwise little differences to patients with
      nonreactive DD. In particular, there were no differences in the course of the
      disorder. However, patients with reactive DD were significantly more often in a
      stable relationship and showed higher values on neuroticism and more pronounced
      dependent and borderline personality accentuations in dimensional personality
      measures. CONCLUSIONS: Reactive DD was not found to have a better prognosis than
      nonreactive DD. However, the results suggest an increased vulnerability for
      interpersonal conflicts in these patients.

PMID- 22480587
TI  - A population-based study of the use of selective serotonin reuptake inhibitors
      before and after introduction of generic equivalents.
AB  - OBJECTIVE: Generic drugs are less expensive than their branded equivalents, but
      receive limited promotion. This study sought to examine how user rates of
      individual selective serotonin reuptake inhibitors (SSRIs) changed after the
      introduction of their generic equivalents. METHOD: Administrative health and
      census data were used to examine the rates of use of all 6 SSRIs from 1996 to
      2009 in the province of Manitoba (population of 1.2 million). The primary outcome
      measure was a comparison of the rates of use in the pre- and post-generic
      periods, using generalized estimating equations. Secondary analyses were
      stratified by specialty of physician prescriber. RESULTS: Escalating rates of use
      of branded SSRIs in the pre-generic period significantly decreased after generic
      versions became available (all Ps < 0.001). Incident use of sertraline and
      paroxetine continued to decrease throughout the post-generic period (1.5% and
      1.9% quarterly decreasing rates, respectively). During the years when generic
      sertraline, fluoxetine, and fluvoxamine were available, their use declined while
      branded paroxetine and citalopram use continued to increase. Use of branded
      citalopram, sertraline, and paroxetine prescribed by general practitioners (GPs)
      increased at rates significantly higher than when prescribed by psychiatrists
      (all Ps < 0.001). CONCLUSION: The introduction of cheaper generic alternatives of
      SSRIs paradoxically resulted in their use diminishing rather than increasing.
      With the exception of escitalopram, branded SSRIs tended to be preferentially
      used, compared with available less expensive generic SSRIs. These patterns were
      more pronounced for prescriptions by GPs.

PMID- 22480588
TI  - Factor structure of borderline personality disorder symptomatology in
      adolescents.
AB  - OBJECTIVE: To examine the factor structure of the Diagnostic and Statistical
      Manual of Mental Disorders (DSM), Fourth Edition, criteria for borderline
      personality disorder (BPD) in a sample of adolescents with a borderline
      symptomatology. METHOD: The latent structure of borderline criteria, assessed
      with the Structured Interview for DSM-IV Personality, was explored with a
      principal factor analysis in a sample of 107 adolescents with a borderline
      symptomatology drawn from a European research project on BPDs. RESULTS: The
      principal component analysis revealed 2 homogeneous factors accounting for 66.8%
      of the variance. The first factor included internally oriented criteria, such as
      avoidance of abandonment, identity disturbance, chronic feeling of emptiness, and
      stress-related paranoid ideation. The second factor included externally oriented
      criteria, such as unstable relationships, impulsivity, suicidal or self
      mutilating behaviours, and inappropriate anger. Affective instability was the
      only criterion loading on both factors. CONCLUSIONS: The results of our study
      suggests that an internal or external dichotomy may be an appropriate way to
      conceptualize the structure of borderline criteria in adolescents with a
      borderline symptomatology, with affective instability being a core feature of BPD
      at this age.

PMID- 22480589
TI  - Risk assessment instruments in clinical practice.
AB  - OBJECTIVE: To determine whether the items in one of the most widely validated
      instruments of violence risk assessment, the Historical-Clinical-Risk Management
      20 (HCR-20), are used in review board hearings to assess the risk of violence by
      people found Not Criminally Responsible on account of Mental Disorder (NCRMD).
      METHOD: This study was conducted from October 2004 to August 2006 in Quebec's
      sole forensic psychiatric hospital and 2 large civil psychiatric hospitals
      designated for the care of people declared NCRMD in the Montreal metropolitan
      area. The risk assessments presented by clinicians at annual review board
      hearings and the boards' rationale for the release or detention of people found
      NCRMD were contrasted with the risk assessments conducted by the research team
      using the HCR-20. The final sample was comprised of 96 men. RESULTS: Very few of
      the risk factors identified by prior research (HCR-20 items) were mentioned in
      the hearing process, whether in clinical reports, discussions during the hearing,
      or in the disposition justification. CONCLUSIONS: The findings confirm that there
      remains a significant gap between research evidence and risk assessment practice.

PMID- 22480590
TI  - [Alcohol and drug consumption in students exposed to the Dawson College shooting:
      a gender-based analysis].
AB  - OBJECTIVE: To study alcohol and drug addiction incidence in students exposed to
      the Dawson College shooting within the 18 months following the event, to identify
      the precursors of a psychoactive substance addiction development while
      considering the severity of event exposure, and to examine whether alcohol use,
      18 months after the event, is related to any of the various posttraumatic stress
      disorder (PTSD) symptom groups. METHOD: The population of this study was
      comprised of all the Dawson College students at the time of the event. Analyses
      were conducted with 854 students enrolled in the college at the time of the
      shooting. RESULTS: Five per cent of women and 7% of men showed, for the first
      time in their life, a problem with substance addiction following the shooting. In
      men, young age, lifetime suicidal ideation, and having seen the killer during the
      shooting are the main precursors of incident accident cases. None of the studied
      precursors were significant in women. Men and women were also different in terms
      of PTSD symptoms predicting alcohol use 18 months after the shooting. CONCLUSION:
      The study highlights the importance of considering a person's sex when studying
      their psychoactive substance use following a trauma.

PMID- 22480591
TI  - Suicidal behaviours in affective disorders: a deficit of cognitive inhibition?
AB  - OBJECTIVE: Suicide has been related to affective disorders. We hypothesized that
      suicide could be associated with cognitive inhibition deficit. Our study aimed to
      systematically review all published articles that examined the relation between
      cognitive inhibition deficit and suicidal behaviours (that is, suicide attempt or
      suicidal ideation) in patients with affective disorders. METHOD: We performed an
      English and French MEDLINE and EMBASE search, ranging from 1970 to 2010, indexed
      under the MeSH terms of suicide, neuropsychology, neuropsychological tests, and
      executive function, combined with the following title and abstract terms:
      neuropsychological functions, executive functioning, and executive performance.
      RESULTS: Among the 164 selected studies, 9 observational studies met the
      selection criteria and were included in the final analysis. The number of
      participants ranged from 57 to 244 (28% to 66%, respectively, were men).
      Executive dysfunction was more frequently found among patients with suicidal
      behaviours. In particular, higher cognitive inhibition deficit was observed in
      depressed subjects with suicide behaviours, compared with depressed subjects
      without any suicidal behaviour. The results of the meta-analysis showed a higher
      impairment in inhibition score, according to the number of perseverations in the
      Wisconsin Card Sorting Test (Cohen d = 0.68) than in inhibition according to the
      time needed to perform the Trail-Making Test part B (d = 0.01) among patients
      with suicidal behaviour, compared with patients with no suicidal behaviour.
      CONCLUSION: This systematic review and meta-analysis showed a positive
      association between cognitive inhibition deficit and suicide attempts in patients
      with affective disorders. Future research should examine whether cognitive
      inhibition deficit precedes the suicidal behaviour.

PMID- 22480592
TI  - Substantial changes in prescription recommendations for bipolar disorder in
      Canada: 2002-2010.
AB  - OBJECTIVES: We examined trends in prescription recommendations for treatment of
      bipolar disorder (BD) in Canada during 2002-2010. METHODS: Data collected by IMS
      Brogan in a database known as the Canadian Disease and Therapeutic Index were
      used for this analysis. These data are collected from a representative physician
      panel who record each drug recommendation and reason for recommendation in their
      practices for 2 consecutive days each calendar quarter of the year. Prescription
      patterns of medications for BD, including lithium, anticonvulsants, antipsychotic
      agents, anxiolytics, and antidepressants, were evaluated both for general
      practitioners and for specialists. RESULTS: The number of prescription
      recommendations for BD increased by 72.1% from 2002 to 2009, and then dropped by
      24.8% from 2009 to 2010. This increase from 2002 to 2009, and subsequent decrease
      from 2009 to 2010, was observed for all classes of medications. The overall
      increase from 2002 to 2010 was statistically significant for the atypical
      antipsychotics (P = 0.04). The largest change for an individual drug during this
      period was a 438% increase in recommendations for quetiapine (P = 0.01).
      CONCLUSIONS: The number of prescription recommendations for BD increased
      substantially from 2002 to 2009 and sharply dropped in the following year. These
      results suggest that the influence of the concept of the bipolar spectrum and its
      promotion may have resulted in a substantial increase in treatment that has
      recently begun to wane.

PMID- 22480593
TI  - The enablers and barriers to the use of direct observation of trainee clinical
      skills by supervising faculty in a psychiatry residency program.
AB  - OBJECTIVE: Studies have reported that medical trainees do not get sufficient
      direct observation. Our study aimed to determine the frequency of direct
      observation and the enablers and barriers to direct observation in the department
      of psychiatry at a large Canadian university. METHOD: Focus groups and interviews
      explored the role and use of direct observation, followed by a survey both of
      faculty and of residents. RESULTS: Direct observation was used in various
      contexts in the residents' last rotation. Missed opportunities are identified.
      Enablers include financial compensation, guidelines, and a discussion at the
      beginning of each clinical rotation. Barriers are identified at the resident,
      faculty, and administrative levels. CONCLUSIONS: Direct observation is used in
      many contexts in psychiatric training. While there are barriers which limit its
      use, our data indicate numerous potential enablers and missed opportunities for
      more observation.

PMID- 22480594
TI  - Comparative proteomics of copper exposure and toxicity in rainbow trout, common
      carp and gibel carp.
AB  - Species specific differences in transporters, chaperones, metal binding proteins
      and other targets are important in metal toxicity. Therefore, we have studied the
      effects of copper exposure on the proteome of gill tissue from Oncorhynchus
      mykiss, Cyprinus carpio and Carassius auratus gibelio, which have different
      sensitivities toward copper. Fish were exposed to the Flemish water quality
      standard for surface waters, being 50MUg/L, for 3 days. Sampled gill tissue was
      subjected to a 2D-Dige and an iTRAQ analysis. While gibel carp showed more
      positive responses such as increased apolipoprotein A-I, transferrin and heat
      shock protein 70, common carp's gill tissue on the other hand displayed a changed
      actin cytoskeleton, and indications of a changed metabolism. These last two
      traits were evident in rainbow trout as well, together with decreased expressions
      of transferrin and albumin. urthermore, the Weighted Gene Co-Expression Network
      Analysis of rainbow trout data revealed a network of 98 proteins related to Cu
      accumulation in gill, of which the occurrence of proteins related to oxidative
      stress, such as superoxide dismutase and cytochrome c were promising.
      Additionally, the outcome of the different proteomics techniques demonstrates the
      usefulness of iTRAQ analysis compared to 2D-Dige and the need for fully annotated
      genomes.

PMID- 22480595
TI  - [Robotic surgery in endometrial cancer: a review].
AB  - Robotic surgery has spread for a few years. This access is now important in
      urologic surgery, especially for prostatic procedures. Development of robotic
      surgery in gynecology is more recent. Gynecologic oncology is probably one of the
      most interesting fields of development of this access. Robotic surgery is
      frequently used in endometrial cancer. As no randomized study is available, it
      seems to be interesting to make a review of retrospective studies. Feasibility
      seems to be high and the learning curve is short (around 20 cases). Operative
      lengths are longer when compared to laparotomy, but are similar or shorter than
      laparoscopy. Robot setting increases the global length of the procedure, but
      decreases with experience. Operative blood loss, as well as transfusion rate are
      decreased when compared to laparotomy, but are similar to those of laparoscopy.
      The overall morbidity rate seems lower than with other approaches. Postoperative
      pain, hospital stay and time to recovery are decreased when compared to
      laparotomy as well as to laparoscopy for some authors. The main limit to the
      diffusion of robotic surgery is accessibility because of its important cost.
      Other limits are pointed out by the most trained teams.

PMID- 22480596
TI  - When, where and how should a patient with community acquired pneumonia be
      admitted?
AB  - Community-acquired pneumonia is the leading cause of death (10-14%) from
      infectious disease and the source of many sepsis and septic shock cases attended
      in the emergency departments. There is great variability in the admission rates
      (22-61%), and 10-20% of such admissions have to be done in the intensive care
      unit. The correct determination of need for admission (when), admission site
      (where) and burden of delivered care (how) will determine the patient's
      prognosis, request for basic and microbiological studies, antibiotic regimen (via
      and duration), clinical follow-up intensity and, consequently, the use of socio
      health resources (costs). This article aims to orient decision-making, taking
      into account the new trends in prognostic evaluation tendencies and the current
      alternatives to the classic hospital admission.

PMID- 22480597
TI  - Relationship of prior antidepressant exposure to long-term prospective outcome in
      bipolar I disorder outpatients.
AB  - OBJECTIVE: The long-term impact of prior antidepressant exposure on the
      subsequent course of bipolar illness remains controversial. METHOD: 139
      outpatients (mean age, 42 years) with bipolar I disorder diagnosed by DSM-IV
      criteria had a detailed retrospective examination of their prior course of
      illness on the National Institute of Mental Health Life Chart Method. Number of
      prior antidepressant trials and total duration of antidepressant exposure were
      assessed. Prospective long-term response (for at least 6 months) to naturalistic
      treatment in the network from 1996 through 2002 was the primary outcome measure
      as it related to prior antidepressant exposure (and other illness variables) by
      logistic regression, with P < .05 used for statistical significance in this post
      hoc analysis. RESULTS: Greater number of antidepressant trials, but not duration
      of antidepressant exposure, was related to prospective nonresponse (P = .0051)
      whether or not antidepressants were covered by concurrent treatment with a mood
      stabilizer or atypical antipsychotic. Poor prospective response was also
      independently related to having had an anxiety disorder and 20 or more prior
      affective episodes. CONCLUSIONS: That the number of antidepressant trials, but
      not duration of antidepressant treatment, was associated with prospective
      nonresponse suggests that it is the repeated use of antidepressants to treat
      episodes of depression that is related to poor prospective response to
      naturalistic treatment. The direction of causality is unclear as to whether more
      antidepressant trials led to this increased treatment resistance or whether a
      difficult course of illness with more episodes and anxiety comorbidity engendered
      more attempts at antidepressant treatment.

PMID- 22480599
TI  - Evidence supporting the role of calpain in the alpha-processing of amyloid-beta
      precursor protein.
AB  - Amyloid plaques are a hallmark of the aging and senile dementia brains, yet their
      mechanism of origins has remained elusive. A central issue is the regulatory
      mechanism and identity of alpha-secretase, a protease responsible for alpha
      processing of amyloid-beta precursor protein (APP). A remarkable feature of this
      enzyme is its high sensitivity to a wide range of cellular stimulators, many of
      which are agonists for Ca(2+) signaling. This feature, together with previous
      work in our laboratory, has suggested that calpain, a Ca(2+)-dependent protease,
      plays a key role in APP alpha-processing. In this study we report that
      overexpression of the MU-calpain gene in HEK293 cells resulted in a 2.7-fold
      increase of the protein levels. Measurements of intracellular calpain enzymatic
      activity revealed that the calpain overexpressing cells displayed a prominent
      elevation of the activity compared to wild-type cells. When the cells were
      stimulated by nicotine, glutamate or phorbol 12,13-dibutylester, the activity
      increase was even more remarkable and sensitive to calpeptin, a calpain
      inhibitor. Meanwhile, APP secretion from the calpain overexpressing cells was
      robustly increased under both resting and stimulated conditions over wild-type
      cells. Furthermore, cell surface biotinylation experiments showed that MU-calpain
      was clearly detected among the cell surface proteins. These data together support
      our view that calpain should be a reasonable candidate for alpha-secretase for
      further study. This model is discussed with an interesting fact that three other
      deposited proteins (tau, spectrin and crystalline) are also the known substrates
      of calpain. Finally we discuss some current misconceptions in senile dementia
      research.

PMID- 22480598
TI  - Plant protein intake is associated with fibroblast growth factor 23 and serum
      bicarbonate levels in patients with chronic kidney disease: the Chronic Renal
      Insufficiency Cohort study.
AB  - BACKGROUND: Protein from plant, as opposed to animal, sources may be preferred in
      chronic kidney disease (CKD) because of the lower bioavailability of phosphate
      and lower nonvolatile acid load. STUDY DESIGN: Observational cross-sectional
      study. SETTING AND PARTICIPANTS: A total of 2,938 participants with CKD and
      information on their dietary intake at the baseline visit in the Chronic Renal
      Insufficiency Cohort Study. PREDICTORS: Percentage of total protein intake from
      plant sources (percent plant protein) was determined by scoring individual food
      items using the National Cancer Institute Diet History Questionnaire (DHQ).
      OUTCOMES: Metabolic parameters, including serum phosphate, bicarbonate (HCO3),
      potassium, and albumin, plasma fibroblast growth factor 23 (FGF-23), and
      parathyroid hormone (PTH), and hemoglobin levels. MEASUREMENTS: We modeled the
      association between percent plant protein and metabolic parameters using linear
      regression. Models were adjusted for age, sex, race, diabetes status, body mass
      index, estimated glomerular filtration rate, income, smoking status, total energy
      intake, total protein intake, 24-hour urinary sodium concentration, use of
      angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and use
      of diuretics. RESULTS: Higher percent plant protein was associated with lower FGF
      23 (P = .05) and higher HCO3 (P = .01) levels, but not with serum phosphate or
      parathyroid hormone concentrations (P = .9 and P = .5, respectively). Higher
      percent plant protein was not associated with higher serum potassium (P = .2),
      lower serum albumin (P = .2), or lower hemoglobin (P = .3) levels. The
      associations of percent plant protein with FGF-23 and HCO3 levels did not differ
      by diabetes status, sex, race, CKD stage (2/3 vs. 4/5), or total protein intake
      (<=0.8 g/kg/day vs. >0.8 g/kg/day; P-interaction >.10 for each). LIMITATIONS:
      This is a cross-sectional study; determination of percent plant protein using the
      Diet History Questionnaire has not been validated. CONCLUSIONS: Consumption of a
      higher percentage of protein from plant sources may lower FGF-23 and raise HCO3
      levels in patients with CKD.

PMID- 22480600
TI  - Electrodiagnostic criteria for Guillain-Barre syndrome: a critical revision and
      the need for an update.
AB  - Electrophysiology plays a determinant role in Guillain-Barre syndrome (GBS)
      diagnosis, classification of the subtypes and in establishing prognosis. In the
      last three decades, different electrodiagnostic criteria sets have been proposed
      for acute inflammatory demyelinating neuropathy (AIDP), acute motor axonal
      neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN). Criteria
      sets for AIDP varied for the parameters indicative of demyelination considered,
      for the cut-off limits and the number of required abnormalities (all a priori
      established) showing different sensitivities. Criteria sets for AMAN and AMSAN
      were proposed on the initial assumption that these subtypes were pathologically
      characterised by simple axonal degeneration. However, some AMAN patients show
      transient conduction block/slowing in intermediate and distal nerve segments,
      mimicking demyelination but without the development of abnormal temporal
      dispersion, named reversible conduction failure (RCF). The lack of distinction
      between RCF and demyelinating conduction block leads to fallaciously classify
      AMAN patients with RCF as AIDP or AMAN with axonal degeneration. Serial
      electrophysiological studies are mandatory for proper diagnosis of GBS subtypes,
      identification of pathophysiological mechanisms and prognosis. More reliable
      electrodiagnostic criteria should be devised to distinguish axonal and
      demyelinating subtypes of GBS, taking into consideration the RCF pattern and
      focussing on temporal dispersion.

PMID- 22480601
TI  - Discriminating preictal and interictal states in patients with temporal lobe
      epilepsy using wavelet analysis of intracerebral EEG.
AB  - OBJECTIVE: Identification of consistent distinguishing features between preictal
      and interictal periods in the EEG is an essential step towards performing seizure
      prediction. We propose a novel method to separate preictal and interictal states
      based on the analysis of the high frequency activity of intracerebral EEGs in
      patients with mesial temporal lobe epilepsy. METHODS: Wavelet energy and entropy
      were computed in sliding window fashion from preictal and interictal epochs. A
      comparison of their organization in a 2 dimensional space was carried out using
      three features quantifying the similarities between their underlying states and a
      reference state. A discriminant analysis was then used in the features space to
      classify epochs. Performance was assessed based on sensitivity and false positive
      rates and validation was performed using a bootstrapping approach. RESULTS:
      Preictal and interictal epochs were discriminable in most patients on a subset of
      channels that were found to be close or within the seizure onset zone.
      CONCLUSIONS: Preictal and interictal states were separable using measures of
      similarity with the reference state. Discriminability varies with frequency
      bands. SIGNIFICANCE: This method is useful to discriminate preictal from
      interictal states in intracerebral EEGs and could be useful for seizure
      prediction.

PMID- 22480602
TI  - tDCS possibly stimulates glial cells.
AB  - OBJECTIVE: Explore the possibility that transcranial direct current stimulation
      (tDCS) of the brain affects glial cells. METHODS: Cable theory is used to
      estimate roughly transmembrane potential in neurons and glial cells. tDCS is
      additionally compared to neuronal stimulation techniques for which the mechanisms
      are well known. RESULTS: Theoretical calculations indicated that tDCS can affect
      the glial transmembrane potential. The change is similar to what is
      physiologically observed in astrocytes during neuronal activation. In neurons,
      transmembrane potential changes are much weaker than the threshold for eliciting
      action potentials. CONCLUSIONS: Based on simplified cable theory, tDCS may affect
      glial cells' transmembrane potential and thereby the balance of
      neurotransmitters. No physiological evidence or proof is available, however.
      SIGNIFICANCE: It is an exciting possibility that tDCS could manipulate glial
      cells because they are active participants in brain function, and have multiple
      essential roles in the human brain. This approach may change greatly the
      therapeutic potential of tDCS, and also affects the safety considerations.

PMID- 22480603
TI  - Are glial cells responsible for transcranial direct current stimulation?

PMID- 22480604
TI  - Building a bridge for nursing education and clinical care in Taiwan--using action
      research and Confucian tradition to close the gap.
AB  - BACKGROUND: Nursing workplaces in Taiwan are unable to retain talent. An
      examination of this problem has revealed that the causes of this phenomenon are
      that nursing education fails to cultivate the skills that meet workplace
      requirements and that there are gap between nursing education and clinical
      practice. OBJECTIVES: This paper is an action research that aims is to design
      educational programs that can close the gap between nursing education and
      clinical practice in Taiwan. DESIGN: In this action research project, 4 action
      cycles were used to design educational programs including concept mapping and
      focused discussion strategies. SETTINGS: Participants were invited to join the
      research in three teaching hospitals and one university. PARTICIPANTS: Two groups
      of participants, student nurses (SN) and nursing staff personnel (NS), were
      sampled and invited to participate in the research. METHODS: Participant
      observation, focus groups, and qualitative interviews were used to collect data.
      Qualitative data were not only profiled by content analysis, but they were also
      compared continuously between the two groups as well as between the 4 cycles.
      RESULTS: The qualitative data collected for the 135 participants were analysed.
      The themes of an effective nursing program were summarized. CONCLUSIONS: Many
      fundamental values of traditional Chinese education have gradually faded due to
      the Westernization of education. In this study, we discovered that Western
      educational models may play a critical role in improving traditionally taught
      nursing education programs.

PMID- 22480606
TI  - [Electromagnetic fields in the hospital everyday].

PMID- 22480607
TI  - Chitosan-based drug nanocarriers: where do we stand?
AB  - Chitosan-based nanocarriers have become one of the most intensively studied
      transmucosal nanometric drug delivery platforms. This is due to a number of
      factors, including their simple and mild preparation technique as well as their
      capacity to associate macromolecules and facilitate their transport across
      mucosal barriers. In this review, we first describe our contribution to the
      origin of chitosan nanocarriers in the mid 90s, and summarize the early work that
      has impacted the development of this delivery technology. Secondly, we present
      our perspective regarding the potential of chitosan nanocarriers for some
      relevant applications: (i) vaccination, (ii) transmucosal protein delivery and
      (iii) gene therapy. Finally, we offer our perspective on the plausible advances
      in this area in the near future.

PMID- 22480608
TI  - ESTRO 2012 strategy meeting: vision for radiation oncology.
AB  - Access to modern radiation oncology treatment programmes is now recognised as an
      essential component of high-quality cancer treatment and central to optimal
      patient care. Looking to the future, ESTRO strongly believes that further
      development of the discipline will be critically important to the future
      strategic development of multidisciplinary cancer care. On behalf of the Board
      and membership of ESTRO, this document outlines the Society's Vision for the
      development of the discipline of Radiation and Clinical Oncology together with
      the associated priority action areas that will collectively and strategically
      direct the Society's activities in the forthcoming years.

PMID- 22480609
TI  - Competencies in radiation oncology: a new approach for education and training of
      professionals for Radiotherapy and Oncology in Europe.

PMID- 22480610
TI  - Weight perceptions and perceived risk for diabetes and heart disease among
      overweight and obese women, Suffolk County, New York, 2008.
AB  - INTRODUCTION: Many Americans fail to accurately identify themselves as overweight
      and underestimate their risk for obesity-related diseases. The purpose of this
      study was to investigate associations between weight perceptions and perceived
      risk for diabetes and heart disease among overweight or obese women. METHODS: We
      examined survey responses from 397 overweight or obese female health center
      patients on disease risk perceptions and weight perceptions. We derived odds
      ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic
      regression analyses to examine predictors of perceived risk for diabetes and
      heart disease. We further stratified results by health literacy. RESULTS:
      Perceiving oneself as overweight (OR, 2.78; 95% CI, 1.16-6.66), believing that
      being overweight is a personal health problem (OR, 2.46; 95% CI, 1.26-4.80), and
      family history of diabetes (OR, 3.22; 95% CI, 1.53-6.78) were associated with
      greater perceived risk for diabetes. Perceiving oneself as overweight (OR, 4.33;
      95% CI, 1.26-14.86) and family history of heart disease (OR, 2.25; 95% CI, 1.08
      4.69) were associated with greater perceived risk for heart disease. Among
      respondents with higher health literacy, believing that being overweight was a
      personal health problem was associated with greater perceived risk for diabetes
      (OR, 4.91; 95% CI, 1.68-14.35). Among respondents with lower health literacy,
      perceiving oneself as overweight was associated with greater perceived risk for
      heart disease (OR, 4.69; 95% CI, 1.02-21.62). CONCLUSION: Our findings indicate
      an association between accurate weight perceptions and perceived risk for
      diabetes and heart disease in overweight or obese women. This study adds to
      research on disease risk perceptions in at-risk populations.

PMID- 22480611
TI  - Design and results of a culturally tailored cancer outreach project by and for
      Micronesian women.
AB  - BACKGROUND: In 2005, approximately 26% of Micronesian women aged 40 or older in
      Hawai'i used mammography for breast cancer screening. We describe an 18-month
      project to increase screening participation in this population by tailoring
      educational materials and using a lay educator approach. COMMUNITY CONTEXT: New
      immigrants to Hawai'i are Marshallese from the Republic of the Marshall Islands
      and Chuukese, Pohnpeians, and Kosraeans from the Federated States of Micronesia.
      In Hawai'i, these 4 groups refer to themselves collectively as Micronesians,
      although each group has its own distinct culture and language. METHODS: From 2006
      through 2007, we applied principles of community-based participatory research-
      trust building, joint assessment, cultural tailoring of materials, and skills
      transfer--to develop and track the reach of Micronesian women lay educators in
      implementing a cancer awareness program among Micronesian women living in
      Hawai'i. OUTCOME: Using our tailored in-language materials, 11 lay educators (5
      Chuukese, 3 Marshallese, 2 Pohnpeians, and 1 Kosraean) provided one-on-one and
      small group in-language cancer information sessions to 567 Micronesian women
      (aged 18-75 years). Among the 202 women aged 40 or older eligible for mammography
      screening, 166 (82%) had never had a mammogram and were assisted to screening
      appointments. After 6 months, 146 (88%) of the 166 had received a mammogram,
      increasing compliance from 18% to 90%. Lay educators reported increases in their
      skills and their self-esteem and want to extend their skills to other health
      issues, including diabetes management and immunization. INTERPRETATION: Tailoring
      materials and using the lay educator model successfully increased participation
      in breast cancer screening. This model may work in other communities that aim to
      reduce disparities in access to cancer screening.

PMID- 22480612
TI  - Increasing evidence-based workplace health promotion best practices in small and
      low-wage companies, Mason County, Washington, 2009.
AB  - INTRODUCTION: Modifiable health risk behaviors such as physical inactivity,
      unhealthy eating, and tobacco use are linked to the most common chronic diseases,
      and chronic diseases contribute to 70% of deaths in the United States. Health
      risk behaviors can be reduced by helping small workplaces implement evidence
      based workplace health promotion programs. The American Cancer Society's
      HealthLinks is a workplace health promotion program that targets 3 modifiable
      health risk behaviors: physical inactivity, unhealthy eating, and tobacco use. We
      evaluated employers' implementation of HealthLinks in small workplaces. METHODS:
      We targeted Mason County, Washington, a rural low-income community with elevated
      obesity and smoking rates. We conducted baseline assessments of workplaces'
      implementation of program, policy, and communication best practices targeting the
      health risk behaviors. We offered tailored recommendations of best practices to
      improve priority health behaviors and helped workplaces implement HealthLinks. At
      6 months postintervention, we assessed changes in best practices implementation
      and employers' attitude about HealthLinks. RESULTS: Twenty-three workplaces
      participated in the program. From baseline to follow-up, we observed significant
      increases in the implementation of physical activity programs (29% to 51%, P =
      .02), health behavior policy (40% to 46%, P = .047), and health information
      communication (40% to 81%, P = .001). Employers favorably rated HealthLinks'
      appeal, relevance, and future utility. CONCLUSION: When offered resources and
      support, small and low-wage workplaces increased implementation of evidence-based
      workplace health promotion best practices designed to reduce modifiable health
      risk behaviors associated with chronic diseases. Results also suggest that
      HealthLinks might be a sustainable program for small workplaces with limited
      resources.

PMID- 22480613
TI  - Molecular basis for the anchoring of proto-oncoprotein Nup98 to the cytoplasmic
      face of the nuclear pore complex.
AB  - The cytoplasmic filament nucleoporins of the nuclear pore complex (NPC) are
      critically involved in nuclear export and remodeling of mRNA ribonucleoprotein
      particles and are associated with various human malignancies. Here, we report the
      crystal structure of the Nup98 C-terminal autoproteolytic domain, frequently
      missing from leukemogenic forms of the protein, in complex with the N-terminal
      domain of Nup82 and the C-terminal tail fragment of Nup159. The Nup82 beta
      propeller serves as a noncooperative binding platform for both binding partners.
      Interaction of Nup98 with Nup82 occurs through a reciprocal exchange of loop
      structures. Strikingly, the same Nup98 groove promiscuously interacts with Nup82
      and Nup96 in a mutually excusive fashion. Simultaneous disruption of both Nup82
      interactions in yeast causes severe defects in mRNA export, while the severing of
      a single interaction is tolerated. Thus, the cytoplasmic filament network of the
      NPC is robust, consistent with its essential function in nucleocytoplasmic
      transport.

PMID- 22480614
TI  - Ultrastructural analysis of IpaD at the tip of the nascent MxiH type III
      secretion apparatus of Shigella flexneri.
AB  - Shigella flexneri is a Gram-negative enteric pathogen that is the predominant
      cause of bacillary dysentery. Shigella uses a type III secretion system to
      deliver effector proteins that alter normal target cell functions to promote
      pathogen invasion. The type III secretion apparatus (T3SA) consists of a basal
      body, an extracellular needle, and a tip complex that is responsible for
      delivering effectors into the host cell cytoplasm. IpaD [Ipa (invasion plasmid
      antigen)] is the first protein to localize to the T3SA needle tip, where it
      prevents premature effector secretion and serves as an environmental sensor for
      triggering recruitment of the translocator protein IpaB to the needle tip. Thus,
      IpaD would be expected to form a stable structure whose overall architecture
      supports its functions. It is not immediately obvious from the published IpaD
      crystal structure (Protein Data Bank ID 2j0o) how a multimer of IpaD would be
      incorporated at the tip of the first static T3SA intermediate, nor what its
      functional role would be in building a mature T3SA. Here, we produce three
      dimensional reconstructions from transmission electron microscopy images of IpaD
      localized at the Shigella T3SA needle tip for comparison to needle tips from a
      Shigella ipaD-null mutant. The results demonstrate that IpaD resides as a
      homopentamer at the needle tip of the T3SA. Furthermore, comparison to tips
      assembled from the distal domain IpaD(Delta192-267) mutation shows that IpaD
      adopts an elongated conformation that facilitates its ability to control type III
      secretion and stepwise assembly of the T3SA needle tip complex.

PMID- 22480615
TI  - HLA techniques: typing and antibody detection in the laboratory of
      immunogenetics.
AB  - The HLA loci are a part of the genetic region known as the major
      histocompatibility complex (MHC). In the last twenty years there has been an
      exponential growth in the application of DNA technology to the field of
      histocompatibility and immunogenetics. Histocompatibility between the patient and
      donor is a prerequisite for the success of haematopoietic stem cell
      transplantation. In haematopoietic stem cell transplantation allele-level typing
      needs to evaluate compatibility for the HLA-A,B,C Class I and DRB1 and DQB1 Class
      II loci in the average transplant program because it is well established that
      mismatches at certain HLA loci between donor-recipients are closely linked to the
      risk of graft versus host disease. Resolution at an antigen level in solid organ
      transplantation is currently sufficient for HLA-A,B and DR antigens and it could
      be achieved by serological or molecular biology techniques. In solid organ
      transplantation the definition of antibodies in the recipient to HLA antigens is
      more important and it was performed primarily by serological technique and more
      recently by solid phase immunoassays that are more sensitive and specific.

PMID- 22480616
TI  - Selective re-expression of beta2 nicotinic acetylcholine receptor subunits in the
      ventral tegmental area of the mouse restores intravenous nicotine self
      administration.
AB  - Beta-2 (beta2) nicotinic acetylcholine receptor subunits have been particularly
      related with nicotine reinforcement. However, the importance of these subunits in
      the chronic aspects of nicotine addiction has not been established. In this study
      we evaluated the role of ventral tegmental area (VTA) beta2 receptor subunits in
      the acquisition and maintenance of nicotine self-administration. We used an
      operant mouse model of intravenous self-administration of different doses of
      nicotine (15, 30, and 60 MUg/kg/infusion) during 10 days in constitutive knockout
      mice lacking beta2 receptor subunits (beta2KO), wild-type (WT) controls, mice
      with beta2 receptor subunits re-expressed in the VTA using a lentiviral vector
      (beta2-VEC), and control knockout mice with a sham injection (KO-GFP). The
      results showed that beta2KO mice did not reliably acquire nicotine self
      administration at any of the doses tested, while WT controls showed dose
      dependent acquisition of this behaviour. beta2-VEC mice readily acquired and
      maintained nicotine self-administration at the effective dose of 15
      MUg/kg/infusion, while sham KO-GFP mice did not. The recovery of the WT phenotype
      by the re-expression of beta2 receptor subunits within the VTA supports the role
      of this specific population in nicotine reinforcement, and reveals that they are
      sufficient for the acquisition and maintenance of systemic nicotine self
      administration.

PMID- 22480617
TI  - Orally administered oleoylethanolamide protects mice from focal cerebral ischemic
      injury by activating peroxisome proliferator-activated receptor alpha.
AB  - Oleoylethanolamide (OEA) is a high-affinity agonist of peroxisome proliferator
      activated receptor alpha (PPARalpha) which may act as an endogenous
      neuroprotective factor. However, it is not clear whether orally administered OEA
      is effective against ischemic brain injury. In our study, transient focal
      cerebral ischemia was induced by middle cerebral artery occlusion for 90 min
      followed by reperfusion. To evaluate its preventive effects, OEA (10, 20 or 40
      mg/kg, ig) was administered for 3 days before ischemia. To evaluate its
      therapeutic effects, OEA (40 mg/kg, ig) was administered at 0.5 or 1h before
      reperfusion or at 0 or 1h after reperfusion. In some experiments, the PPARalpha
      antagonist MK886 (10mg/kg, ig) was administered 0.5h before OEA. Neurological
      deficit score, infarct volume and brain edema degree were determined at 24h after
      reperfusion. Blood-brain barrier (BBB) disruption was evaluated by Evans blue
      (EB) leakage at 6h after reperfusion. Real-time RT-PCR and western blot were
      performed to detect PPARalpha mRNA and protein expression. Oral OEA pretreatment
      improved neurological dysfunction reduced infarct volume and alleviated brain
      edema in a dose-dependent manner; the most effective dose was 40 mg/kg. The
      therapeutic time is within 1h after reperfusion. OEA also increased PPARalpha
      mRNA and protein expression in the ischemic brain. The PPARalpha antagonist MK886
      abolished the protective effects of OEA. In conclusion, our results indicate that
      orally administered OEA protects against acute cerebral ischemic injury in mice,
      at least in part by activating PPARalpha.

PMID- 22480619
TI  - Postoperative changes in the superficial temporal artery and the external carotid
      artery duplex sonography after extra-intracranial bypass surgery in European
      Moyamoya disease.
AB  - INTRODUCTION: Despite Duplex ultrasonography being a noninvasive, easily
      repeatable, readily available and economical tool, this examination and its
      normal ranges are rarely described in Moyamoya disease (MMD). METHODS: Duplex
      ultrasonography examinations of the superficial temporal artery (STA) and
      external carotid artery (ECA) were performed preoperatively, postoperatively
      (within 30 days) and as follow-up exams (6 months postoperatively) after 32
      cerebral revascularization procedures in 20 European patients with MMD. RESULTS:
      A significant higher mean diastolic flow of STA compared to preoperative values
      was found in postoperative (p<.000) and follow-up exams (p<.001) in Duplex
      ultrasonography. Postoperative and follow-up Duplex sonography of STA also showed
      a significantly higher mean systolic flow compared to preoperative values (p<.05
      and p<.05). Also ECA showed significantly changes after bypass surgery (p<.05).
      CONCLUSION: Duplex ultrasonography of STA is a reliable and non-invasive tool to
      investigate hemodynamic changes after bypass surgery and to detect bypass patency
      in European patients with MMD.

PMID- 22480620
TI  - Modification of altered ankle motor control after stroke using focal application
      of botulinum toxin type A.
AB  - STUDY DESIGN: Blinded, placebo-controlled, prospective clinical trial. PURPOSE:
      To examine the effects of botulinum toxin type A (BTX-A) injections into plantar
      flexor muscles in stroke patients with equinovarus gait. SUBJECTS: 15 post-stroke
      and 10 matched neurologically intact subjects. METHODS: Modified Ashworth Scale
      (MAS) and Fugl-Meyer assessment of physical function scale scores along with
      surface EMG collected before and up to 12 weeks after BTX-A injections to plantar
      flexor muscle motor points in stroke subjects. Saline placebo injections were
      performed in a subset of stroke subject group. RESULTS: MAS scores were decreased
      at 4, 8 and 12 weeks but F-M scores did not improve until 12 weeks post
      injection. Multi-muscle EMG patterns showed the return of volitional dorsiflexor
      activity in 11 and a decrease of antagonistic and distant coactivation in all but
      one of the 15. CONCLUSIONS: BTX-A is effective in reducing antagonistic and
      distant muscle activation that impedes volitional dorsiflexion.

PMID- 22480621
TI  - Role of oxidative stress in diabetes-mediated vascular dysfunction: unifying
      hypothesis of diabetes revisited.
AB  - Oxidative stress is recognized as a key participant in the development of
      diabetic complications in the vasculature. One of the seminal studies advancing
      the role of oxidative stress in vascular endothelial cells proposed that
      oxidative stress-mediated diversion of glycolytic intermediates into pathological
      pathways was a key underlying element in the development of diabetic
      complications. It is widely recognized that flux through glycolysis slows during
      diabetes. However, several bottlenecks develop in the glycolytic pathway,
      including glucose transport, phosphofructokinase, glyceraldehyde-3-phosphate
      dehydrogenase and pyruvate kinase. Of these limiting steps in glycolysis,
      glyceraldehyde-3-phosphate dehydrogenase is most sensitive to oxidative stress,
      leading to the hypothesis that glyceraldehyde-3-phosphate inactivation by
      ribosylation underlies the diversion of glycolytic intermediates into
      pathological pathways. However, recent studies question the mechanism underlying
      the effect of reactive oxygen species on key enzymes of the glycolytic pathway.
      The present review critiques the major premises of the hypothesis and concludes
      that further study of the role of oxidative stress in the development of diabetes
      mediated vasculature dysfunction is warranted.

PMID- 22480622
TI  - A review of pharmacologic management and prevention strategies for delirium in
      the intensive care unit.
AB  - BACKGROUND: The prevalence of delirium has been estimated at anywhere between 10%
      and 30% in general medical patients and in upwards of 80% in patients who are
      admitted to an intensive care unit (ICU). Given the high prevalence of delirium
      in the ICU population, it should not be surprising that a large percentage of
      psychiatric consults arise from this setting. While the mainstay of pharmacologic
      management of delirium centers on neuroleptic medications, such as haloperidol,
      recent studies using alternate agents have shown varying levels of promise.
      OBJECTIVE: Our purpose is to outline the major prospective studies looking at the
      efficacy of pharmacologic management and prevention strategies for delirium
      exclusively in adult ICU patients. Both conventional and novel
      pharmacotherapeutic interventions are discussed. METHOD: Articles were obtained
      using the MEDLINE/PUBMED database looking specifically at pharmacologic
      interventions for delirium in the intensive care unit. A search was performed
      using the key words"delirium," "intensive care unit," "treatment," and
      "prophylaxis." The authors limited their search to prospective studies,
      specifically randomized trials (both placebo-controlled and non-controlled) in
      the adult ICU population, and eliminated retrospective and observational studies.
      Relevant citations from the previously mentioned articles were also included in
      the review. CONCLUSION: There is a plethora of studies on pharmacologic
      management strategies in general medical patients with delirium. Findings from
      these studies are often extrapolated to the ICU population; however, when looking
      at studies limited to ICU patients with delirium, there are far fewer credible
      prospective studies.

PMID- 22480623
TI  - Resolution of catatonia after treatment with stimulant medication in a patient
      with bipolar disorder.

PMID- 22480624
TI  - Cannabinoid hyperemesis syndrome: a case series and review of previous reports.
AB  - BACKGROUND: Cannabis is the most commonly used illicit substance worldwide.
      Cannabinoids or cannabinoid receptor agonists are often used to treat nausea,
      vomiting, and anorexia. However, in recent years, several medical journals have
      published reports of patients with nausea and vomiting thought to be induced by
      chronic cannabis use. OBJECTIVE: The authors seek to inform readers about
      Cannabinoid Hyperemesis Syndrome (CHS). METHOD: The authors describe four
      patients with chronic cannabis abuse, episodic, intractable nausea and vomiting,
      and compulsive hot water bathing. Previous cases of CHS are reviewed,
      pathophysiology is hypothesized, and difficulties with making the diagnosis are
      discussed. CONCLUSION: CHS should be strongly considered in the differential
      diagnosis of patients with intractable vomiting and/or compulsive hot water
      bathing.

PMID- 22480625
TI  - Is fibromyalgia an endocrine/endorphin deficit disorder? Is low dose naltrexone a
      new treatment option?

PMID- 22480626
TI  - Time-driven effects on parsing during reading.
AB  - The phonological trace of perceived words starts fading away in short-term memory
      after a few seconds. Spoken utterances are usually 2-3s long, possibly to allow
      the listener to parse the words into coherent prosodic phrases while they still
      have a clear representation. Results from this brain potential study suggest that
      even during silent reading, words are organized into 2-3s long 'implicit'
      prosodic phrases. Participants read the same sentences word by word at different
      presentation rates. Clause-final words occurring at multiples of 2-3s from
      sentence onset yielded increased positivity, irrespective of presentation rate.
      The effect was interpreted as a closure positive shift (CPS), reflecting
      insertion of implicit prosodic phrase boundaries every 2-3s. Additionally, in
      participants with low working memory span, clauses over 3s long produced a
      negativity, possibly indicating increased working memory load.

PMID- 22480627
TI  - The anatomy of the subscapular nerves: a new nomenclature.
AB  - We propose a new nomenclature for the consistent, additional nerves that branch
      from the posterior cord of the brachial plexus. We hope this will aid the plexus
      surgeon and the evolution of plexus reconstruction for both obstetric and adult
      cases of injury.

PMID- 22480628
TI  - Development and psychometric properties of the Shared Decision Making
      Questionnaire--physician version (SDM-Q-Doc).
AB  - OBJECTIVE: To develop and psychometrically test a brief instrument for assessing
      the physician's perspective of the shared decision-making process in clinical
      encounters. METHODS: We adapted the 9-item Shared Decision Making Questionnaire
      (SDM-Q-9) for patients to generate a new version for physicians (SDM-Q-Doc). The
      physician version was tested in clinical encounters between 29 physicians and 324
      patients in German outpatient care contexts. Analyses of the extent to which the
      instrument was accepted, the reliability of the instrument, and the factorial
      structure of the scale were performed. RESULTS: Physicians showed a high level of
      acceptance toward the SDM-Q-Doc. Item discrimination parameters were above .4 for
      all but one item. An analysis of internal consistency yielded a Cronbach's alpha
      of .88. Factor analysis confirmed a one-dimensional structure. CONCLUSION: The
      results of this study suggest that the SDM-Q-Doc is a well-accepted and reliable
      instrument for assessing the physician's perspective during SDM processes in
      clinical encounters. To our knowledge, the SDM-Q-Doc is the first
      psychometrically tested scale available for assessing the physician's
      perspective. PRACTICE IMPLICATIONS: The SDM-Q-Doc can be used in studies that
      analyze the effectiveness of the implementation of SDM and as a quality indicator
      in quality assurance programs and health service assessments.

PMID- 22480629
TI  - Patients feeling severely affected by multiple sclerosis: how do patients want to
      communicate about end-of-life issues?
AB  - OBJECTIVE: Investigate multiple sclerosis patients' desire to communicate with
      their physicians about their disease progression and end-of-life issues. METHODS:
      Persons meeting the inclusion criteria of feeling severely affected by MS were
      invited via the German MS society to complete a needs questionnaire. Replies to
      questions on physician empathy and wishes about communication regarding disease
      progression and death and dying were quantitatively analyzed. Endpoints (point
      1+2/4+5) of 5-point-likert scales are summarized under results. RESULTS: 573 of
      867 questionnaires meeting our criteria were analyzed. In response to a general
      question 64% (n = 358) indicated a wish for disease progression and death and
      dying to be addressed by their doctor. A majority (76%, n = 427) considered it
      important that progression of their disease be discussed, while 44% (n = 246)
      regard addressing death and dying as unimportant. No objective disease criteria
      could be identified to explain the wish for communicating end-of-life issues.
      Doctors who were retrospectively viewed as avoiding raising critical aspects of
      the illness were perceived as less empathetic (p < 0.001). CONCLUSION: People
      with MS have a desire to talk about progression of their disease with their
      doctors. PRACTICE IMPLICATIONS: Physicians should be empathetic in raising
      critical aspects of the patients' illness individually.

PMID- 22480630
TI  - Reanalysis of the data of the article "impaired lung function after intubation
      and mechanical ventilation for surgical ligation of the ductus arteriosus in
      preterm infants" by Dzukou et Al.

PMID- 22480632
TI  - Timing of preoperative aspirin discontinuation and outcome after elective
      coronary artery bypass graft surgery: a role of platelet function assessment.

PMID- 22480633
TI  - Dizziness leads to an unexpected diagnosis.

PMID- 22480634
TI  - Surgical management of ischemic mitral regurgitation: relearning our lessons.

PMID- 22480635
TI  - Effect of long-term thoracic epidural analgesia on refractory angina pectoris: a
      10-year experience.
AB  - OBJECTIVES: In patients with refractory angina, the adjuvant effects of long-term
      home self-treatment with thoracic epidural analgesia on angina, quality of life,
      and safety were evaluated. DESIGN: A prospective, consecutive study. SETTING: A
      university hospital. PARTICIPANTS AND INTERVENTION: Between January 1998 and
      August 2007, 152 consecutive patients with refractory angina began treatment with
      thoracic epidural analgesia by intermittent injections of bupivacaine (139 home
      treatment and 13 palliative). Data were collected until August 2008; therefore,
      the follow-up for each patient was between 1 and 9 years. MEASUREMENTS AND MAIN
      RESULTS: All but 7 of the patients improved symptomatically, and the improvement
      was maintained throughout the period of treatment (median = 19 months; range, 1
      month-8.9 years). After 1 to 2 weeks, the median (interquartile range [IQR])
      Canadian Cardiovascular Society angina class decreased from 4.0 (3.0-4.0) to 2.0
      (1.0-2.0), the mean +/- standard deviation frequency of anginal attacks decreased
      from 36 +/- 19 to 4.4 +/- 6.8 a week, the nitroglycerin intake decreased from
      27.7 +/- 15.7 to 2.7 +/- 4.9 a week, and the median (IQR) overall self-rated
      quality of life assessed by the visual analog scale increased from 25 (20-30) to
      70 (50-75) (all p < 0.001). About one-third of the patients had a dislodgement of
      the epidural catheter. Apart from 1 epidural hematoma that appeared in 1 patient
      with a previously undiagnosed bleeding defect, no other serious catheter-related
      complications occurred. CONCLUSIONS: Long-term self-administered home treatment
      with thoracic epidural analgesia is a safe, widely available adjuvant treatment
      for patients with severe refractory angina. It produces symptomatic relief of
      angina and improves quality of life. The technical development of the method to
      protect the catheter against dislodgement is needed.

PMID- 22480636
TI  - Effects of long-term incarceration: a statistical comparison of two expert
      assessments of two experts at the beginning and the end of incarceration.
AB  - Several studies have been conducted on the effects of long-term imprisonment on
      mental health but only few with a longitudinal study design. Those with
      longitudinal design often have a very short observation period. In this study the
      data of 87 long-term prisoners have been compared over an average period of 14.6
      years. A statistical comparison of two expert assessments of two experts at the
      beginning and the end of incarceration was made. Changes of mental disorders, of
      personality and intelligence tests and of physical diseases amongst others have
      been included in the analysis. The overall rate of psychological disorders
      decreased. Adjustment disorder had been initially identified in 25.2%.
      Personality test results described a stabilization of traits like depressive
      attitude, emotional instability and a decrease of hostility. Neither significant
      changes on the outcomes of the intelligence test nor significant changes of
      physical health were found. Though a decrease of psychological morbidity is
      described, the overall numbers of psychological disorders remain high compared to
      the non incarcerated population. A damaging effect of long-term imprisonment
      could not be proven by this study.

PMID- 22480637
TI  - [Aging: the chemistry of a flexible biological clock].

PMID- 22480638
TI  - [Aging, an issue of the XXI(st) century].

PMID- 22480639
TI  - [Virulence effectors target key proteins of interactome networks of host plant
      cells].

PMID- 22480640
TI  - [HIP/PAP, a new drug for acute liver failure].

PMID- 22480641
TI  - [Dense inhibitory neuronal networks revealed by two-photon photoactivation of
      RuBi-Glutamate].

PMID- 22480642
TI  - [The Yin and the Yang of senescence: is it possible to age without developing
      cancer?].

PMID- 22480643
TI  - [A new player in PML-mediated cellular senescence: TBX2 gets into the loop].

PMID- 22480644
TI  - [FoxO proteins in the control of stem cells].

PMID- 22480645
TI  - [The aryl hydrocarbon receptor, a molecular link between diet and immunity].

PMID- 22480646
TI  - [MITF: a genetic key to melanoma and renal cell carcinoma?].

PMID- 22480647
TI  - [Characterisation of Burkholderia pseudomallei Lethal Factor 1 (BLF1). A
      breakthrough against melioidosis].

PMID- 22480648
TI  - [A tale of stolen kiss in muscle].

PMID- 22480649
TI  - [Membrane traffic, a new actor in axon guidance].

PMID- 22480650
TI  - [Sirtuin 1, hepatic steatosis and liver cancer].

PMID- 22480651
TI  - [How to turn a silent proapoptotic gene in a potent antitumoral target in
      colorectal cancer].

PMID- 22480652
TI  - [How to define old age: successful aging and/or longevity].
AB  - In half a century, the number of nonagenarians and/or centenarians has
      dramatically increased, particularly due to the increase in life expectancy at
      old age. However, successful aging is more important than longevity. All along
      their life, people can act to preserve their health, their physical and mental
      abilities as well as their autonomy. This requires a healthy diet, having
      physical and intellectual appropriate activities and a right use of medical care.
      Finally, maintaining a social role and a raison d'etre in old age are also major
      factors in successful aging.

PMID- 22480653
TI  - [Cellular senescence and the myth of Janus].
AB  - Cellular senescence is, essentially, a permanent proliferation arrest induced by
      various cellular stresses or inappropriate stimuli. This arrest, which is
      associated with dramatic changes in cell morphology, metabolism and gene
      expression, involves a complex signalling network aiming at stable inactivation
      of CDKs, major cell cycle regulators. Notably, several tumour suppressors, such
      as p53, pRb or p16(Ink4a), play key roles both in the initiation of the
      senescence program and in its maintenance, which often involves epigenetic
      changes. While having widely recognized roles in tumour suppression and wound
      healing, senescence, like the roman god Janus, recently revealed another darker
      face. Mostly due to altered secretion phenotype favouring inflammation, senescent
      cells strongly influence surrounding tissue contributing to the development of
      age-related pathologies, including cancer.

PMID- 22480654
TI  - [The diversity of aging models].
AB  - Most of the signalling pathways involved in aging regulation have been recently
      found well conserved at various levels throughout the evolution. Taking this into
      account, a diversity of model organisms, including worms, rodents, and lemurs as
      well, allows to address different questions: how to understand the interactions
      between genetic and environmental factors while challenging theories of aging, to
      preserve hearing integrity, to fight against senescence of neural stem cells, or
      to explore brain fitness from gene expression to cognitive and social behavior?
      Here are the main issues that can be considered, stressing the complementarities
      of the models. The differentiation of aging physiological aspects from those
      induced by age-related pathologies will also be specified. By emphasizing recent
      ability of technologies to promote new aging insights, we discuss towards a
      better understanding of mechanisms governing aging.

PMID- 22480655
TI  - [Mild stress as a means to modulate aging: from fly to human?].
AB  - Hormesis is the phenomenon by which adaptive responses to low doses of otherwise
      harmful conditions improve the functional ability of organisms. Some mild
      stresses have beneficial effects on longevity, aging and resistance to strong
      stresses (heat or cold shocks, infection) in Drosophila flies. Studies on rodents
      are indeed scarce but mild stress seems to be effective in humans because, for
      instance, patients suffering from angina have a higher survival when confronted
      with a heart attack. A few studies, in less tragic situations however, suggest
      that mild stress could have positive effects in elderly people. Performing more
      experiments on the effects of mild stress in humans would help to know whether it
      could be used in therapy or to improve healthspan of elderly.

PMID- 22480656
TI  - [Metabolic homeostasis as the cornerstone of aging].
AB  - During the last decade, studies aimed at investigating genes and molecular
      pathways involved in aging have been very fruitful and led to the identification
      of several mechanisms responsible for aging. Overall, those results put forward
      the capacity of cells and organisms to sense and respond to stress, as a critical
      factor for a healthy and long life. Those molecular pathways are tightly linked
      with the overall metabolism of an organism. Indeed, environmental stresses
      trigger a plethora of defense mechanisms which are energy demanding while still
      the organism has to allocate energy for the maintenance of basic functions. So
      all along our life, we have to adapt to different stresses while optimizing
      energy use. This review aims at highlighting data from the literature that
      support the crucial role of metabolism as a modulator of aging and age-associated
      disease, as illustrated by the beneficial effect of dietary restriction on
      longevity and cancer development.

PMID- 22480657
TI  - [Aging and the control of the insulin-FOXO signaling pathway].
AB  - Aging is a complex process that is accompanied by the onset of a series of age
      related diseases, including Alzheimer's disease. Aging is controlled by a
      combination of genetic and environmental factors. Among the genes that regulate
      aging, the insulin-FOXO signaling pathway plays a central role, as this pathway
      regulates lifespan in multiple species, such as worms, flies, and mice. In
      humans, exceptional longevity - being a centenarian - is also associated with
      genetic variation in this insulin-FOXO pathway. Recent evidence indicates that
      the FOXO family of transcription factors plays a key role in the self-renewal of
      adult and embryonic stem cells, which could contribute to tissue regeneration.
      Understanding the mechanisms underlying aging should help better prevent and
      treat age-dependent diseases.

PMID- 22480658
TI  - [Case management in gerontology: new practice, new issue].

PMID- 22480659
TI  - [Is there any clinical utility to DTC-style personal genome profiling?].

PMID- 22480660
TI  - [Autism, the untraceable gene: from science to business].

PMID- 22480661
TI  - A divalent DNA vaccine based on Sia10 and OmpU induces cross protection against
      Streptococcus iniae and Vibrio anguillarum in Japanese flounder.
AB  - Streptococcosis and vibriosis caused by Streptococcus iniae and Vibrio
      anguillarum respectively have affected fish culture industries around the world.
      Previous studies have indicated that the S. iniae antigen Sia10 and the V.
      anguillarum outer membrane protein OmpU, when used as DNA vaccines, induce
      protection in turbot (Scophthalmus maximus) and Asian seabass (Lates calcarifer)
      respectively. In this study, with an effort to develop effective vaccines against
      S. iniae and V. anguillarum, we constructed three DNA vaccines based on Sia10 and
      OmpU and examined their immune effects in a model of Japanese flounder
      (Paralichthys olivaceus), which in China is known to suffer from both
      streptococcosis and vibriosis. Of the three DNA vaccines constructed in this
      study, pIDSia10 and pIDOmpU express Sia10 and OmpU respectively, while pSiVa1
      expresses Sia10 and OmpU as two individual proteins translated from a single
      bicistronic mRNA transcript. At 7 and 28 days post-vaccination, vaccine plasmids
      and expression of the vaccine-encoding genes were detected in the muscle, spleen,
      kidney, and liver of the vaccinated fish. Immunocolloidal gold electron
      microscopy detected production of Sia10 and OmpU proteins in pIDSia10- and
      pIDOmpU-vaccinated fish respectively, while both Sia10 and OmpU proteins were
      detected in pSiVa1-vaccinated fish. At one and two months post-vaccination, fish
      vaccinated with pIDSia10 and pSiVa1 exhibited comparable relative percent of
      survival (RPS) rates (80%-87%) following lethal S. iniae challenge. Similar
      protection rates were produced by fish vaccinated with pIDOmpU and pSiVa1
      following lethal V. anguillarum challenge. Immunological analysis showed that (i)
      all vaccines induced specific serum antibody production which enhanced complement
      mediated bactericidal activity, and (ii) pSiVa1 modulated the expression of a
      wide spectrum of immune relevant genes in a time-dependent manner. Together these
      results indicate that pSiVa1 is an effective bivalent vaccine that induces strong
      cross protection in flounder against S. iniae and V. anguillarum.

PMID- 22480662
TI  - Effect of garlic powder on the growth of commensal bacteria from the
      gastrointestinal tract.
AB  - Garlic (Allium sativum) is considered one of the best disease-preventive foods.
      We evaluated in vitro the effect of a commercial garlic powder (GP), at
      concentrations of 0.1% and 1% (w/v), upon the viability of representative gut
      bacteria. In pure culture studies, Lactobacillus casei DSMZ 20011 was essentially
      found to be resistant to GP whereas a rapid killing effect of between 1 and 3 log
      CFU/ml reduction in cell numbers was observed with Bacteroides ovatus,
      Bifidobacterium longum DSMZ 20090 and Clostridium nexile A2-232. After 6h
      incubation, bacterial numbers increased steadily and once the strains became
      resistant they retained their resistant phenotype upon sub-culturing. A colonic
      model was also used to evaluate the effect of GP on a mixed bacterial population
      representing the microbiota of the distal colon. Lactic acid bacteria were found
      to be more resistant to GP compared to the clostridial members of the gut
      microbiota. While for most bacteria the antimicrobial effect was transient, the
      lactobacilli showed a degree of resistance to garlic, indicating that its
      consumption may favour the growth of these beneficial bacterial species in the
      gut. Garlic intake has the potential to temporarily modulate the gut microbiota.

PMID- 22480663
TI  - A randomized placebo-controlled trial of D-cycloserine to enhance exposure
      therapy for posttraumatic stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a complex and debilitating
      anxiety disorder, and, although prolonged exposure therapy has been proven
      effective, many patients remain symptomatic after treatment. In other anxiety
      disorders, the supplementary use of D-cycloserine (DCS), a partial agonist at the
      glutamatergic N-methyl-D-aspartate receptor, showed promise in enhancing
      treatment effects. We examined whether augmentation of prolonged exposure therapy
      for PTSD with DCS enhances treatment efficacy. METHODS: In a randomized, double
      blind, placebo-controlled trial we administered 50 mg DCS or placebo 1 hour
      before each exposure session to 67 mixed trauma patients, recruited from regular
      referrals, with a primary PTSD diagnosis satisfying DSM-IV criteria. RESULTS:
      Although DCS did not enhance overall treatment effects, the participants having
      received DCS did show a stronger treatment response. Exploratory session-by
      session analyses revealed that DCS yielded higher symptom reduction in those
      participants that had more severe pretreatment PTSD and needed longer treatment.
      CONCLUSIONS: The present study found preliminary support for the augmentation of
      exposure therapy with DCS, specifically for patients with more severe PTSD
      needing longer treatment.

PMID- 22480665
TI  - The HAPPY study: development and reliability of a parent survey to assess
      correlates of preschool children's physical activity.
AB  - Correlates of preschool children's physical activity across all domains of the
      social ecological model have previously been reported in the literature. However,
      there is a scarcity of reliable instruments designed to capture such correlates
      in preschool-aged children. OBJECTIVES: This study reports the development, and
      assessment of the test-retest and internal reliability of a comprehensive proxy
      survey instrument designed to measure correlates of preschool children's physical
      activity across the three domains of the social ecological model. DESIGN: Study
      one included data from 47 parents of preschool aged (3-5 years) children who
      completed the survey on two occasions. Study two included data from 943
      participants who completed the survey as part of the larger Healthy Active
      Preschool Years Study. METHODS: A comprehensive search of the literature and a
      series of focus groups were used to identify potential correlates for inclusion
      in the survey. Study one investigated the test-retest reliability of the survey;
      study two investigated internal reliability. Test-retest reliability was assessed
      using Kappa statistics and percent agreement for categorical variables, and
      intraclass correlation for continuous variables. Internal reliability was
      assessed using Cronbach's alpha. RESULTS: In total, 230 items, summed and
      composite scores were assessed. Of those items, 190 (83%) showed acceptable
      reliability. The majority of items in each domain of the social ecological model-
      individual (75%), social (81%) and physical environment (90%)--showed acceptable
      reliability. CONCLUSIONS: The Healthy Active Preschool Years parent proxy survey
      shows good reliability and is appropriate for use with the target population.
      Future studies should investigate validity of the constructs in the survey.

PMID- 22480664
TI  - Molecular tools and approaches for optogenetics.
AB  - The mammalian brain poses a formidable challenge to the study and treatment of
      neuropsychiatric diseases, owing to the complex interaction of genetic,
      epigenetic, and circuit-level mechanisms underlying pathogenesis. Technologies
      that facilitate functional dissection of distinct brain circuits are necessary
      for systematic identification of disease origin and therapy. Recent developments
      in optogenetics technology have begun to address this challenge by enabling
      precise perturbation of distinct cell types based on molecular signatures,
      functional projections, and intracellular biochemical signaling pathways. With
      high temporal precision and reversible neuromodulation, optogenetics promises to
      improve existing disease models and advance our understanding of psychiatric
      conditions. In this review, we describe the current state of molecular
      optogenetic tools and future directions of development.

PMID- 22480666
TI  - Increases in the availability of prescribed opioids in a Canadian setting.
AB  - BACKGROUND: The nonmedical use of prescribed opioids (POs) has increased across
      North America over the past decade. Our objective was to identify changes in the
      availability of POs and other illicit drugs among drug users in a Canadian
      setting. METHODS: Information on the availability of illicit drugs was collected
      in standardized interviews from a large observational research program involving
      illicit drug users in Vancouver, British Columbia from 2006 to 2010. The primary
      outcome was the perceived availability of a set of six POs (aspirin/oxycodone,
      hydromorphone, oxycodone, morphine, acetaminophen/codeine and methadone) among
      individuals reporting ever using POs. Availability was measured in three levels:
      not available, delayed availability (available >=10 min), and immediate
      availability (available <10 min). Multivariate ordinal logistic regression models
      were executed to estimate the trend in PO availability, controlling for
      individual characteristics hypothesized to influence availability. RESULTS: 1871
      individuals were followed during the study period (2006-2010), including 583
      (31.2%) women. The availability of POs increased over time, regardless of changes
      in the characteristics of cohort entrants. These increases were observed while
      the availability of traditional drugs of abuse (e.g., heroin and cocaine)
      remained constant. The adjusted odds of delayed availability vs. unavailability
      were between 34% (hydromorphone) and 71% (acetaminophen/codeine) greater in each
      calendar year. DISCUSSION: The availability of POs among drug users in a Canadian
      setting increased markedly over a relatively short timeframe, despite persistent
      and high availability of heroin and cocaine. Further study is required to
      determine the context of use of POs, associated harms, as well as policy
      responses to increasing availability.

PMID- 22480667
TI  - Brief case finding tools for anxiety disorders: validation of GAD-7 and GAD-2 in
      addictions treatment.
AB  - BACKGROUND: Anxiety disorders are the most common mental health problems and
      often co-exist with substance use. Little evidence exists to support the use of
      brief screening tools for anxiety disorders in routine addictions treatment. This
      is the first study to test the validity and reliability of GAD-7 and GAD-2 in an
      outpatient drugs treatment population. METHODS: A sample of 103 patients
      completed brief screening questionnaires and took part in structured diagnostic
      assessments using CIS-R. A subgroup of 60 patients completed retests after 4
      weeks. The results of brief questionnaires were compared to those of gold
      standard diagnostic interviews using Receiver Operating Characteristic (ROC)
      curves. Psychometric properties were also calculated to evaluate the validity and
      reliability of self-completed questionnaires. RESULTS: A GAD-7 score >= 9 had a
      sensitivity of 80% and specificity of 86% for any anxiety disorder, also
      displaying adequate temporal stability at repeated measurements (intra-class
      correlation=0.85) and high internal consistency (Cronbach's alpha=0.91). A GAD-2
      score >= 2 had 94% sensitivity and 53% specificity, with adequate internal
      consistency (0.82). CONCLUSIONS: GAD-7 adequately detected the presence of an
      anxiety disorder in drug and alcohol users; although this study was limited by
      sample size to determine its reliability for specific diagnoses. Results in this
      small sample suggest that GAD-7 may be a useful screening tool in addiction
      services, although replication in a larger sample is warranted.

PMID- 22480668
TI  - Influence of degenerative changes of intervertebral disc on its material
      properties and pathology.
AB  - OBJECTIVE: To investigate the material properties of normal and degenerated
      intervertebral discs (IVDs) and examine the effect of degenerative changes on IVD
      pathology. METHODS: A computer-based online search was undertaken to identify
      English articles about material properties of IVDs published from January 1950 to
      2011 in PubMed database. The retrieved keywords included material properties,
      intervertebral disc and degeneration. Based on the principles of reliability,
      advancement and efficiency, the obtained data were primarily examined, and the
      original source was retrieved to read the full-text. Repetitive articles were
      excluded. The data of material properties of normal and degenerated IVDs were
      summarized and analyzed by meta-analysis. RESULTS: The data of Young's modulus,
      Poisson's ratio, shear modulus, hydraulic permeability and intradiscal pressure
      of normal and degenerated IVDs were obtained. Compared with normal IVDs, the
      Young's modulus and shear modulus of annulus fibrosus and nucleus pulposus were
      higher in degenerated IVDs, the Poisson's ratio was lower while the hydraulic
      permeability and intradiscal pressure were higher. Besides, the degeneration
      related alterations in IVDs had an influence both on itself and other spinal
      structures, leading to diseases such as bulging disc, discogenic pain and spinal
      stenosis. Meanwhile, the heavy mechanical loading and injury indicated important
      pathways to IVD degeneration. CONCLUSIONS: To a certain extent, the degenerative
      changes of IVD influence its material properties. And the degeneration-related
      alterations of composition can cause structural failure of IVDs, leading to
      injuries and diseases.

PMID- 22480669
TI  - Laser in situ keratomileusis surgery is not safe for military personnel.
AB  - OBJECTIVE: To investigate the relationship between eye injury and laser in-situ
      keratomileusis (LASIK) surgery in military personnel. METHODS: This retrospective
      study collected the data from 27 evacuation hospitals of Chinese army. All
      medical records of eye injuries in military personnel admitted to the 27
      hospitals between January 2006 and December 2010 were reviewed. Patients'detailed
      information was analyzed, including the injury time, place, type, cause, as well
      as examination, treatment and outcome. RESULTS: There were 72 eye-injured
      patients who had been treated by LASIK before. The incidence was rising year by
      year. Among them, 69 patients were diagnosed with mechanical ocular injury and 3
      with non-mechanical ocular injury; 29 patients had traumatic flap-related
      complications and 21 patients need surgery. There was statistical difference when
      compared with those having no refractive surgery history. Visual acuity recovered
      well at discharge. CONCLUSION: There is a high risk of potential traumatic flap
      problems after LASIK and it is not recommended in army service.

PMID- 22480670
TI  - Timing of internal fixation and effect on Schatzker IV-VI tibial plateau
      fractures.
AB  - OBJECTIVE: To study the effect of internal fixation performed at different times
      on therapeutic outcomes of Schatzker IV-VI tibial plateau fractures. METHODS: The
      clinical data of 42 cases of Schatzker IV-VI tibial plateau fractures treated in
      our department were analyzed retrospectively. Among these 42 patients, 21
      received surgical treatment within 12 h after injury (Group I), the other 21 were
      first treated by traction or plaster fixation followed by a delayed internal
      fixation after soft tissue swelling subsided (Group II). The surgical time,
      complications, length of hospital stay, cost of hospitalization, and time for
      fracture union, as well as functional recovery were analyzed and compared between
      the two groups. RESULTS: After 10-28 months follow-up (mean 16.5 months), except
      5 cases who lost to follow-up, no differences were found between the two groups
      regarding surgical time, preoperative and postoperative complications, healing
      time or the Hospital for Special Surgery (HSS) score at the end of follow-up, but
      significant differences were found in the length of hospital stay, cost of
      hospitalization and HSS score at 3 months after operation (P less than 0.05).
      CONCLUSION: Under certain conditions, early internal fixation for Schatzker IV-VI
      tibial plateau fracture is feasible, which can shorten the length of hospital
      stay, decrease the cost of hospitalization and promote early functional
      rehabilitation.

PMID- 22480671
TI  - Meta-analysis of mNGF therapy for peripheral nerve injury: a systematic review.
AB  - OBJECTIVE: To assess the efficacy and safety of mouse nerve growth factor (mNGF)
      in patients with peripheral nerve injury. METHODS: Such electronic database as
      Cochrane Library (Issue 1, 2011), Medline (1950-2011), Embase (1980-2011),
      National Knowledge Infrastructure (1979-2011) were searched and meanwhile
      relevant journals such as Chinese Journal of Orthopaedics, Chinese Journal of
      Microsurgery, Chinese Journal of Neurosurgery, etc were searched as well  to
      collect all randomized controlled trials and quasi-randomi- zed controlled trials
      of mNGF on patients with peripheral nerve injury. The quality of included studies
      was assessed according to the criteria recommended by the Cochrane Handbook for
      Systematic Reviews of Interventions and the data were extracted by two reviewers
      independently. Meta-analysis was conducted by RevMan 5.1 software. RESULTS: Forty
      one studies involving 3 304 patients with peripheral nerve injury were included.
      The results of meta-analysis showed that: (1) the total effective rate of
      peripheral nerve injury treatment in mNGF group was ob- viously higher than that
      in control group (OR equal to 6.36, 95% CI 4.96-8.15, P less than 0.01); (2) the
      scores of activities of daily living (ADL) in mNGF group was significantly higher
      than that in control group (weighted mean difference equal to 1.97, 95% CI 1.33
      2.61, P less than 0.01); (3) the incidence of adverse reaction in mNGF group was
      higher than that in control group, (OR equal to 1.66, 95% CI 1.61-2.38, P equal
      to 0.006), but the adverse effects were mild, which could be relieved without
      specific treatment or just given symptomatic treatment, and disappeared at the
      end of treatment. CONCLUSIONS: The mNGF therapy is effective for peripheral nerve
      injury. It can obviously improve patient's ADL. Though the incidence of adverse
      reaction in mNGF treatment group is higher than that in control group, this does
      not influence the treatment outcomes.

PMID- 22480672
TI  - Endoscopy-assisted cerebral falx incision via unilateral approach for treatment
      of dissymmetric bilateral frontal contusion.
AB  - OBJECTIVE: To investigate the clinical features and treatment strategy of
      dissymmetric bilateral frontal contusion, and to summarize our experience in
      treating these patients by minimally invasive surgery. METHODS: Over the past 3
      years, we have treated a total of 31 patients with dissymmetric bilateral frontal
      contusion using endoscopy-assisted unilateral cerebral falx incision. Other 30
      patients treated by routine bilateral approaches within the same period were
      taken as control. RESULTS: Seventeen cases (54.8%) in the unilateral operation
      group survived and were in good condition, 8 (25.8%) had moderate disability, 4
      (12.9%) had severe disability, 1 (3.2%) was in vegetative state, and 1 (3.2%)
      died. Compared with the control group, the Glasgow Outcome Scale score was not
      significantly different in the unilateral operation group, but the operation
      time, blood transfusion volume, the length of hospital stay, the incidences of
      mental disorder and olfactory nerve injury were greatly reduced in the unilateral
      operation group. CONCLUSIONS: Endoscopy-assisted unilateral cerebral falx
      incision can shorten the operation time, reduce surgical trauma and complications
      in treatment of patients with dissymmetric bilateral frontal contusion. It can
      obviously diminish the chance of delayed intracerebral hematoma and subsequently
      minimize the incidences of subfalcial and centrencephalic herniation.

PMID- 22480673
TI  - Epidemiological features of 1 281 patients with head injuries arising from the
      2008 Wenchuan earthquake.
AB  - OBJECTIVE: To analyze the epidemiological features of patients with head injuries
      in the 2008 Wenchuan earthquake. METHODS: Medical records of patients with head
      injuries who were admitted to 14 hospitals in Deyang, Mianyang and Chengdu cities
      after the earthquake were retrospectively analyzed. The patients'age, gender,
      cause of injury, diagnosis, and outcome were analyzed retrospectively. RESULTS: A
      total of 1 281 patients with 807 males and 474 females were included. According
      to Glasgow Coma Scale score at admission, 1 029 patients presented with mild
      injury, 161 moderate injury and 91 severe injury. The major cause of injuries
      (83%) was bruise by collapsed buildings. Open head injuries accounted for 60.8%.
      A total of 720 patients underwent surgical treatment. Good recovery was achieved
      in 1 056 patients, moderate disability in 106, severe disability in 71, coma in
      29 and death in 19. CONCLUSIONS: In this series, male patients were more than
      female patients. The main cause of injury was hit by falling objects due to
      building collapse. Minor and open craniocerebral injuries were most common. The
      epidemiological features of head injuries in Wenchuan earthquake may be helpful
      to preparation for future rescue.

PMID- 22480674
TI  - Establishment of a blunt impact-induced brain injury model in rabbits.
AB  - OBJECTIVE: To establish an animal model to replicate the blunt impact brain
      injury in forensic medicine. METHODS: Twenty-four New Zealand white rabbits were
      randomly divided into control group (n equal to 4), minor injury group (n equal
      to 10) and severe injury group (n equal to 10). Based on the BIM-II Horizontal
      Bio-impact Machine, self-designed iron bar was used to produce blunt brain
      injury. Two rabbits from each injury group were randomly selected to monitor the
      change of intracranial pressure (ICP) during the impacting process by pressure
      microsensors. Six hours after injury, all the rabbits were dissected to observe
      the injury morphology and underwent routine pathological examination. RESULTS:
      Varying degrees of nervous system positive signs were observed in all the injured
      rabbits. Within 6 hours, the mortality rate was 1/10 in the minor injury group
      and 6/10 in the severe injury group. Morphological changes consisted of different
      levels of scalp hematoma, skull fracture, epidural hematoma, subdural hematoma,
      subarachnoid hemo- rrhage and brain injury. At the moment of hitting, the ICP was
      greater in severe injury group than in mild injury group; and within the same
      group, the impact side showed positive pressure while the opposite side showed
      negative pressure. CONCLUSIONS: Under the rigidly-controlled experimental
      condition, this animal model has a good reproducibility and stable results.
      Meanwhile, it is able to simulate the morphology of iron strike-induced injury,
      thus can be used to study the mechanism of blunt head injury in forensic
      medicine.

PMID- 22480675
TI  - Barrier stabilizing mediators in regulation of microvascular endothelial
      permeability.
AB  - Increase of microvascular permeability is one of the most important pathological
      events in the pathogenesis of trauma and burn injury. Massive leakage of fluid
      from vascular space leads to lose of blood plasma and decrease of effective
      circulatory blood volume, resulting in formation of severe tissue edema,
      hypotension or even shock, especially in severe burn injury. Fluid resuscitation
      has been the only valid approach to sustain patient's blood volume for a long
      time, due to the lack of overall and profound understanding of the mechanisms of
      vascular hyperpermeability response. There is an emerging concept in recent years
      that some so-called barrier stabilizing mediators play a positive role in
      preventing the increase of vascular permeability. These mediators may be released
      in response to proinflammatory mediators and serve to restore endothelial barrier
      function. Some of these stabilizing mediators are important even in quiescent
      state because they preserve basal vascular permeability at low levels. This
      review introduces some of these mediators and reveals their underlying signaling
      mechanisms during endothelial barrier enhancing process.

PMID- 22480676
TI  - Implant-induced microdamage in osteoporotic bone.
AB  - With the increase of elderly population, more and more implant operations need to
      be performed in osteoporotic bone, while different forms of microdamage will be
      produced in peri-implant bone intraoperatively, including high- and low-density
      diffuse damages, as well as linear cracks. The length and location of the
      microcracks are the main factors in affecting the biomechanical performance of
      bone. Suppression of bone remodeling by bisphosphonates may lead to microdamage
      accumulation, which is often accompanied with the decrease of bone strength and
      the increase of bone fragility. Microdamage can be repaired by bone remodeling or
      mineralization to maintain the strength and structural integrity. Both remo-
      deling and mineralization can affect the bone quality and long-term implant
      stability. In this paper, we make a brief summary of some important issues and
      research progresses in this field.

PMID- 22480677
TI  - Transarterial coil embolization in treatment of gross hematuria following self
      inflicted stab wound in a horseshoe kidney.
AB  - Horseshoe kidney is an uncommon anomaly of the urinary system with an increased
      risk of injury during penetrating and blunt abdominal traumas. Self-inflicted
      abdominal stab wound, a rare type of abdominal injury, accounts for only a small
      percentage of suicidal attempts and may be infrequently encountered by physicians
      in trauma centers. Psychiatric disorders and alcohol or drug abuse are common
      risk factors in cases of self-stabbing. Here we report a rare case of self
      stabbing of a horseshoe kidney. The case was a 19-year-old man with self
      inflicted abdominal stab wound who was referred to our department of radiology
      due to re-occurred gross hematuria three days after exploratory laparotomy and
      surgical repair of injured abdominal organs. A horseshoe kidney was incidentally
      found in the patient's abdominal computed tomography. Renal angiography revealed
      active contrast extravasation from one of the segmental arteries. Selective
      transarterial embolization with a coil was successfully performed to control the
      hematuria.

PMID- 22480678
TI  - Bilateral inferior dislocation of the hip---a case report.
AB  - Inferior dislocation of the hip is the ra- rest type in hip dislocation. Very few
      cases have been reported in the anglophonic literature, most of which involved
      the pediatric age group. Surprisingly, we came across a 30-year-old patient with
      a bilateral inferior hip dislocation. He had sustained a road traffic accident
      and the attitude of both hip joints was flexion and abduction. The diagnosis was
      confirmed by radiographs which revealed the long axis of the femur at an angle of
      110 (right) degrees and 100 (left) degrees respectively away from the axis.
      Closed reduction under sedation was successfully performed. Skin traction for a
      period of 6 weeks was advised and the follow-up revealed an excellent result. We
      present the details of this case, the first of its kind along with a review of
      the literature, discussing the various modes and mechanisms of injury inducing
      inferior dislocation of the hip.

PMID- 22480679
TI  - Maggot therapy for repairing serious infective wound in a severely burned
      patient.
AB  - The larvae of musca domestica were put in use to discard the dead tissue of a
      case of severe burn. A total of 50 000 aseptic maggots were put onto the
      infective wound surface, and aseptic dressings overlaid the surface. Three days
      later, another 20 000 maggots were put onto the wound for the second therapy.
      After twice maggot debridement, most necrotic muscle tissues of the wound were
      cleaned up, and eventually fresh granulation tissue grew and later the wound was
      covered and healed by 3 times of skin grafting. The result demonstrates that
      maggot therapy is safe and effective with no adverse complications except pain.

PMID- 22480680
TI  - Brodie's abscess of medial distal femoral condyle after a thorn prick: rare
      clinical presentation.
AB  - Thorn prick injuries are generally conceded frivolous and rarely demand medical
      attention. Howbeit deep seated injuries are well described in the literature. We
      presented a case of thorn prick injury to the knee that manifested as Brodie's
      abscess of the medial distal femoral condyle and synovitis. Magnetic resonance
      imaging (MRI) and ultrasonography could only construe the affliction but not spot
      the thorn. Arthrotomy was undertaken for exploration and debridement. Empirical
      therapy with initial systemic Cefotaxime and subsequent Ofloxacin worked well
      after the surgery. Deep seated injuries by a thorn prick may take a protracted
      and torpid course. Thorough curettage of the bony lesion and debridement are
      vital for proper manage- ment.

PMID- 22480681
TI  - Does spatial cueing affect line bisection in chronic hemianopia?
AB  - Patients with homonymous hemianopia often show a contralesional shift towards
      their blind field when bisecting horizontal lines ("hemianopic line bisection
      error", HLBE). The reasons for this spatial bias are not well understood and
      debated. Cueing of spatial attention modulates line bisection significantly in
      patients with visuospatial neglect. Moreover, recent evidence showed that
      attention training significantly improves deficits of visual search in
      hemianopia. Here, we tested in 20 patients with chronic homonymous hemianopia (10
      left-sided, 10 right-sided) without visual neglect, 10 healthy control subjects,
      10 neurological control patients, and 3 patients with left visuospatial neglect
      and leftsided hemianopia whether spatial cueing influences the HLBE. Subjects
      indicated verbally the midpoint of horizontal lines in a computerized line
      bisection task under four experimental cue positions (cue far left, mid-left, mid
      right or far-right within the horizontal line). All 20 hemianopic patients showed
      the typical HLBE towards their blind field, while the two control samples showed
      only a small but significant leftward shift (pseudoneglect). None of the 4 cueing
      manipulations had a significant effect on the HLBE in the hemianopic patients.
      Moreover, no differential effects of cueing on line bisection results were
      obtained when analyzed in lesion subgroups of hemianopic patients with
      circumscribed occipital lesions (N=8) as contrasted with patients having more
      extended (occipito-temporal or temporal) lesions (N=12). This null-effect
      contrasts with marked cueing effects observed in 3 neglect patients with left
      hemianopia in the same tasks, showing the principal efficacy of our cueing
      manipulation. These results argue against attentional explanations of the HLBE.

PMID- 22480682
TI  - Hemifacial spasm, vertebrobasilar dolichoectasia and neurofibromatosis type 1.
AB  - Hemifacial spasm (HFS) is usually produced by compression of the facial nerve by
      tortuous blood vessels at the root exit zone, including vertebrobasilar
      dolichoectasia (VBD). Neurofibromatosis type 1 (NF1) is an autosomal dominant
      disorder with a variety of symptoms, affecting mainly the skin and nervous
      system. Cerebrovascular abnormalities are becoming a recognized complication of
      the disease and the most constantly described lesions are stenosis and occlusions
      affecting the internal carotid artery. VBD has rarely been associated with NF1.
      We report a 38-year-old female patient with HFS produced by VBD with NF1
      presenting with other cerebrovascular abnormalities associated with this disease.
      We discuss the possible association between these three entities, assuming that a
      causal relationship may be established and that VBD is part of the spectrum of
      vascular abnormalities caused by NF1 in this patient.

PMID- 22480683
TI  - Structural studies of arginine induced enhancement in the activity of T7 RNA
      polymerase.
AB  - Addition of arginine enhances the activity of the enzyme T7 RNA polymerase.
      Different methods have been employed to understand the enhancement in the light
      of arginine induced alteration of the tertiary structure. The increase in
      activity of the enzyme reaches a maximum value around a concentration of 125 mM
      arginine. Fluorescence, circular dichroism and dynamic light scattering studies
      indicate an alteration in the tertiary structure of the enzyme. Enthalpy change
      as a function of input concentration of arginine to a fixed concentration of the
      enzyme (5 MUM) shows a dip at 100 mM concentration of arginine. Differential
      scanning calorimetric studies of the denaturation of the enzyme in absence and
      presence of arginine indicates arginine induced destabilization of the C-terminal
      domain of the enzyme. Structural alterations induced by arginine have been
      compared with those induced by the denaturant guanidine hydrochloride.

PMID- 22480684
TI  - Inhibitory role of E2F-1 in the regulation of tumor suppressor p53 during DNA
      damage response.
AB  - Appropriate regulation of DNA damage response is pivotal for maintaining genome
      stability. p53 as well as E2F-1 plays a critical role during DNA damage response,
      however, the physiological significance of their interaction has been elusive. In
      the present study, we found that E2F-1 has an inhibitory effect on p53 during
      adriamycin (ADR)-mediated DNA damage response. Upon ADR exposure, p53 and E2F-1
      were markedly induced at protein and mRNA levels in p53-procifient U2OS and
      HCT116 cells, and formed a stable complex as examined by co-immunoprecipitation
      experiments. Of note, chromatin immunoprecipitation (ChIP) experiments revealed
      that ADR-mediated induction coincides with the efficient recruitment of p53 and
      E2F-1 onto the promoters of p53-target genes, such as p21(WAF1) and BAX.
      Subsequent RT-PCR and luciferase reporter assays demonstrated that E2F-1 strongly
      attenuates p53-dependent transactivation of p53-target genes. Importantly, siRNA
      mediated knockdown of E2F-1 stimulated apoptosis in response to ADR, which was
      associated with an accelerated response of p21(WAF1) and BAX. Collectively, our
      present findings suggest that E2F-1 participates in p53-mediated DNA damage
      response and might have a checkpoint function to limit overactive p53.

PMID- 22480685
TI  - Lidamycin induces neural differentiation of mouse embryonic carcinoma cells
      through down-regulation of transcription factor Oct4.
AB  - Lidamycin is a potential anti-cancer drug, which is widely used in a variety of
      human cancer types. It has been reported that lidamycin inhibited mouse embryonic
      carcinoma (EC) cells growth through down-regulation of embryonic stem (ES) cell
      like genes. In this study, whether 0.01 nM lidamycin induces neuronal
      differentiation of mouse EC cells was investigated. It was observed that
      lidamycin decreased transcription factor Oct4, and increased both p21 mRNA and
      protein expression in P19 EC cells. Furthermore, luciferase assay showed that
      lidamycin activated p21 promoter activity through suppression of Oct4, and
      Chromatin immunoprecipitation (ChIP) assay confirmed that binding of
      transcription factor Oct4 to the p21 promoter decreased in lidamycin-exposed
      cells. Knockdown of Oct4 resulted in neuron-like differentiation and up
      regulation of p21 expression. In accordance, overexpression of Oct4 blocked
      neural differentiation and down-regulated p21 in lidamycin-treated P19 cells.
      Taken together, these results suggested that neuronal differentiation of EC cells
      induced by lidamycin was associated with the inhibition of Oct4 expression and
      the activation of p21 transcription. Our results have provided a novel mechanism,
      in which lidamycin led to cancer cell differentiation.

PMID- 22480686
TI  - Porphyromonas gingivalis lipopolysaccharide induces miR-146a without altering the
      production of inflammatory cytokines.
AB  - Lipopolysaccharide (LPS) from Porphyromonas gingivalis, an oral Gram-negative
      bacterium, acts as a virulence factor for periodontal disease. Although P.
      gingivalis LPS does not induce proinflammatory cytokines as strongly as
      Escherichia coli LPS, it is still able to exploit negative Toll-like receptor
      (TLR) regulatory pathways and facilitate pathogen persistence. Recent reports
      suggest that microRNAs (miRNAs) are also involved in the regulation of TLR
      signaling. Here, we demonstrate that P. gingivalis LPS strongly induces miRNA
      146a expression in THP-1 cells and THP-1-derived macrophages. However, the
      inhibition or overexpression of miR-146a, through the transfection of a specific
      inhibitor or precursor, respectively, had little effect on cytokine production in
      macrophages stimulated with P. gingivalis LPS. Moreover, the expression of
      interleukin-1 associated-kinase-1 (IRAK-1) and tumor-necrosis factor (TNF)
      receptor-associated factor-6 (TRAF6), potential target molecules of miR-146a,
      were not affected by the stimulation with P. gingivalis LPS. Because TLR
      signaling induces various negative regulators, these results call into question
      the role of miR-146a in cells stimulated with TLR ligands.

PMID- 22480687
TI  - A selective estrogen receptor modulator inhibits tumor necrosis factor-alpha
      induced apoptosis through the ERK1/2 signaling pathway in human chondrocytes.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine mediating
      inflammatory as well as cell death activities, and is thought to induce
      chondrocytic chondrolysis in inflammatory and degenerative joint diseases.
      Selective estrogen receptor modulators (SERMs), such as raloxifene, which are
      commonly used in clinical settings act as estrogen agonists or antagonists. It is
      assumed that estrogens have a potential role in cartilage protection; however,
      the precise molecular mechanism for the protective effects of estrogens is
      unclear. This study was designed to examine whether raloxifene inhibits TNF-alpha
      induced apoptosis in human chondrocytes and to clarify the mechanisms involved.
      We also investigated the signaling pathways responsible for the anti-apoptotic
      effect of raloxifene. Apoptosis in chondrocytes was determined by DNA
      fragmentation assay and caspase-3 activation. Raloxifene significantly inhibited
      TNF-alpha-induced caspase-3 activation and cell DNA fragmentation levels in
      chondrocytes. The inhibitory effect of raloxifene was abolished by the estrogen
      receptor antagonist ICI 182,780. Extracellular signal-regulated kinase 1/2
      (ERK1/2) regulates apoptosis, acting as an apoptotic or anti-apoptotic signal.
      TNF-alpha-induced apoptosis was significantly enhanced by the ERK1/2 pathway
      inhibitor PD98059. Raloxifene stimulated a further increase in ERK1/2
      phosphorylation in TNF-alpha-treated chondrocytes. Furthermore, the anti
      apoptotic effects of raloxifene were inhibited by PD98059. In addition, the anti
      apoptotic effects of raloxifene were completely abolished in ERK1/2 siRNA-treated
      chondrocytes. These results suggest that raloxifene prevents caspase-3-dependent
      apoptosis induced by TNF-alpha in human chondrocytes by activating estrogen
      receptors and the ERK1/2 signaling pathway.

PMID- 22480689
TI  - The role of the GABA(B) receptor and calcium channels in a Drosophila model of
      Parkinson's Disease.
AB  - Transgenic Drosophila melanogaster carrying the human gene for alpha synuclein is
      an animal model for the study of Parkinson's Disease. Climbing activity in these
      flies is reduced as a result of the effect of this protein on the locomotor
      activity of the transgenic fly. L-DOPA and gamma amino butyric acid (GABA)
      reverse the loss of this activity when placed in the food fed to these flies.
      While muscimol, a GABA(A) receptor agonist has no effect in this system, baclofen
      and the allosteric agonists CG 7930 and GS 39783 which affect the GABA(B)
      receptor reverse this activity. This latter effect is eliminated when these
      compounds are fed in conjunction with the GABA(B) receptor antagonist 2
      hydroxysaclofen. In addition, fendiline which is a Ca(++) receptor blocker also
      reverses the loss of climbing ability. Because there is a calcium channel close
      to the GABA(B) receptor on the cell surface, these data are indicative of a
      relationship between the roles of the GABA(B) receptor, the calcium channel and
      the effect of alpha-synuclein on the motor activity of the transgenic fly.

PMID- 22480688
TI  - LPS activates ADAM9 dependent shedding of ACE from endothelial cells.
AB  - Angiotensin-I converting enzyme (ACE) is a zinc dependent peptidase with a major
      role in regulating vasoactive peptide metabolism. ACE, a transmembrane protein,
      undergoes proteolysis, or shedding, by an as yet unidentified proteinase to
      release a catalytically active soluble form of the enzyme. Physiologically,
      soluble ACE in plasma is derived primarily from endothelial cells. We demonstrate
      that ACE shedding from confluent endothelial cells is increased in response to
      bacterial lipopolysaccharide, but not phorbol esters. Characterisation of
      lipopolysaccharide stimulated shedding showed that there is a lag phase before
      soluble ACE can be detected which is sensitive to inhibitors of translation, NF
      kappaB, TNFalpha and TNFR-I/II. The shedding phase is less sensitive to these
      inhibitors, but is ablated by BB-94, a Matrix Metalloproteinase (MMP)/A
      Disintegrin and Metalloproteinase (ADAM) inhibitor. Tissue Inhibitor of
      Metalloproteinase (TIMP) profiling suggested a requirement for ADAM9 in
      lipopolysaccharide induced ACE shedding, which was confirmed by depletion with
      siRNA. Transient transfection of ADAM9 and ACE cDNAs into HEK293 cells
      demonstrated that ADAM9 requires both membrane anchorage and its catalytic domain
      to shed ACE.

PMID- 22480690
TI  - Lithium and oxidative stress lessons from the MPTP model of Parkinson's disease.
AB  - Lithium has been successfully employed therapeutically for treatment of bipolar
      depressive illness; however, its mechanism of action is poorly understood.
      Recently, it has been demonstrated by us that lithium can prevent 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) dopaminergic neurotoxicity in mice. From
      analyzing the pattern of protection in various parameters, we suggest that
      lithium protects against MPTP-induced depletion of striatal dopamine (DA) by
      preventing free radical-induced inactivation of tyrosine hydroxylase (TH), the
      rate limiting enzyme in dopamine synthesis. Possible neuroprotective effect of
      lithium against H(2)O(2)-induced cell death was assessed in human neuroblastoma;
      SH-SY5Y cell line. Pretreatment with LiCl (2mM and 4mM) for 7 days protected
      against H(2)O(2) neurotoxicity in a dose-dependent manner. However, this
      protection could not be achieved through short-term incubation with LiCl. In
      agreement; we found that lithium lacks immediate antioxidant activity using the
      in vitro lipid peroxidation essay indicating that not acute but chronic treatment
      with lithium allows cells to deal better with oxidative stress.

PMID- 22480691
TI  - Gonadotropin-releasing hormone treatment improves locomotor activity, urinary
      function and neurofilament protein expression after spinal cord injury in
      ovariectomized rats.
AB  - It was reported that the hypothalamic decapeptide, gonadotropin-releasing hormone
      (GnRH) produces neurotrophic effects and that the spinal cord possesses GnRH
      receptors. The aim of the present study was to determine whether administration
      of GnRH improves locomotor activity, urinary function and neurofilament (NFs)
      protein expression after spinal cord injury (SCI) in ovariectomized rats. SCI was
      induced by balloon inflation model resulting in paraplegia. Locomotion was
      evaluated according to the Basso, Beattie, and Bresnahan Scale. Rats were
      subjected to bladder compression, twice daily until bladder reflex was
      established. NFs of 68, 160 and 200 kDa from spinal cords were analyzed by
      electrophoresis. GnRH (60 MUg/kg) or physiologic NaCl solution was administered
      at 1 day after SCI and then daily for 15 days and the functional evaluation was
      realized for 5 weeks. Our results indicate that locomotor activity, restoration
      of urinary dysfunction and NFs expression of 160 and 200 kDa were improved in SCI
      animals given GnRH compared to those without treatment. These findings suggest
      that GnRH acts as a neurotrophic factor and may be used as a potential
      therapeutic agent for treatment of SCI.

PMID- 22480692
TI  - Differential adaptive changes on serotonin and noradrenaline transporters in a
      rat model of peripheral neuropathic pain.
AB  - Serotonin and noradrenaline reuptake inhibitors have shown to produce
      antinociceptive effects in several animal models of neuropathic pain. In the
      present work, we have analyzed the density of brain and spinal serotonin and
      noradrenaline transporters (5-HTT and NAT) in a rat model of neuropathic pain,
      the spinal nerve ligation (SNL). Quantitative autoradiography revealed a
      significant decrease in the density of 5-HTT ([(3)H]citalopram binding) at the
      level of the lumbar spinal cord following 2 weeks of neuropathic surgery (lamina
      V, -40%: 6.01+/-0.64 nCi/mg tissue in sham-animals vs 3.59+/-1.56 in SNL-animals;
      lamina X, -30%: 9.10+/-2.00 vs 6.40+/-1.93 and lamina IX, -22%: 12.01+/-2.41 vs
      9.42+/-1.58). By contrast, NAT density ([(3)H]nisoxetine binding) was
      significantly increased (lamina I-II, +34%: 2.20+/-0.45 vs 2.96+/-0.65; lamina V,
      +57%: 1.34+/-0.28 vs 2.11+/-0.66; and lamina IX, +58%: 2.39+/-0.71 vs 3.78+/
      1.10). At supraspinal structures, SNL induced adaptive changes only in the
      density of 5-HTT (septal nuclei, +33%: 10.18+/-2.03 vs 13.53+/-1.14; CA3 field of
      hippocampus, +18%: 6.94+/-1.01 vs 8.21+/-0.81; paraventricular thalamic nucleus,
      +21%: 15.18+/-1.88 vs 18.35+/-2.08; lateral hypothalamic area, +40%: 12.68+/-1.90
      vs 17.8+/-2.55; ventromedial hypothalamic nuclei, +19%: 7.16+/-0.92 vs 8.55+/
      0.40; and dorsal raphe nucleus, +15%: 35.22+/-3.88 vs 40.68+/-3.11). Thus, we
      demonstrate, in the SNL model of neuropathic pain, the existence of opposite
      changes in the spinal expression of 5-HTT (down-regulation) and NAT (up
      regulation), and the presence of supraspinal adaptive changes (up-regulation)
      only on 5-HTT density. These findings may help understanding the pathogeny of
      neuropathic pain and the differential analgesic action of antidepressants
      targeting 5-HTT and/or NAT transporters.

PMID- 22480693
TI  - Self-paced and externally triggered rhythmical lower limb movements: a functional
      MRI study.
AB  - Self-paced rhythmical lower limb movement is an important component of locomotive
      motion in humans. External stimuli are known to facilitate the generation of
      rhythmical motion. The importance of such self-paced and externally triggered
      movements is widely recognized, and these movements of the upper limbs have been
      studied in detail. However, the difference in neural mechanisms between the self
      paced and externally triggered movements of the lower limbs is not clear even in
      healthy subjects. The present study investigated the neural regions involved in
      the lower limb movements by using functional magnetic resonance imaging (fMRI).
      The subjects were fixed face-up to an MRI bed and performed lower limb movements
      that mimicked walking under self-paced and externally triggered conditions. The
      results showed that the supplementary motor area, sensorimotor cortex and
      cerebellum were involved in both types of movement, but the basal ganglia and the
      thalamus were selectively recruited for the self-paced lower limb movement. These
      results are compatible with those of previous studies on the control of the lower
      limbs, and on upper limb movement under self-paced and externally triggered
      conditions.

PMID- 22480695
TI  - Termination differences in the primary sensorimotor cortex between the medial
      lemniscus and spinothalamic pathways in the human brain.
AB  - The medial lemniscus (ML) and its thalamocortical pathway is responsible for
      proprioception, in contrast, the spinothalamic tract (ST) and its thalamocortical
      pathway is the neural tract for pain and body temperature. Therefore, the ML
      pathway plays a crucial role in skillful movements and may be more linked to
      motor function than the ST pathway. We investigated the differences in the
      distribution of the primary motor cortex (M1) and the primary somatosensory
      cortex (S1) between the ML and ST pathways. Adults (mean age: 40.4 years, range:
      21-61 years) were recruited for this study. The seed masks for the ML and ST
      pathways were given on the color map of the medulla according to the known
      anatomy and waypoint masks were placed on the ventro-postero-lateral nucleus of
      the thalamus. The volume of ML pathway did not show any difference between the M1
      (10.94) and S1 (13.02) (p>0.05). By contrast, the mean voxel number of the ST
      pathway in the M1 (18.25) and S1 (27.38) showed significant difference between
      the M1 and S1 (p<0.05). As for relative voxel number percentage of the M1
      compared to the S1, the ML pathway (84%) was significantly higher than ST pathway
      (67%) (p<0.05). We found that more neural fibers of the ML pathway were
      terminated in the M1 relative to the S1 compared to the SLP, and this may be
      linked to the inherent execution of movements of the M1.

PMID- 22480694
TI  - Urethral flow-responsive afferents in the cat sacral dorsal root ganglia.
AB  - Although sensory feedback from the urethra plays an integral role in the
      regulation of lower urinary tract function, little is known about the properties
      of flow-responsive primary afferent neurons. The purpose of this study was to
      characterize the activity of sacral afferents that responded to fluid flow
      through the urethra. Single neuron action potentials were recorded
      extracellularly from the S1 and S2 dorsal root ganglia in eight cats anesthetized
      with alpha-chloralose. 21 of 116 cells responded to urethral flow but not to
      mechanical palpation of the perineum, 22 responded to both urethral flow and
      palpation, and 27 responded to palpation only. 34 of the 43 flow-responsive cells
      exhibited a firing response to 10 ml flow boluses that could be fit using a power
      function: FR(t)=a*(t)(b)+c, where FR is firing rate, t is time, and a, b and c
      are constants. In all 34 cells the 'b' term was negative, indicating that the
      firing rate slowed over the time course of the urethral flow. In 16 of the 24
      cells that were recorded during at least four different flow rates, a power
      function provided a good fit of the relationship between firing rate and flow
      rate: FR(flow)=k*(flow)(p)+q, where k, p and q are constants. In each of these 16
      cells the 'p' term was positive, indicating that the firing rate tended to
      increase with increases in flow rate. These are the first data to characterize
      the properties of flow-responsive afferents in the cat, and reveal properties
      that parallel those of other afferents.

PMID- 22480697
TI  - Subcutaneous emphysema and pneumomediastinum due to carbon dioxide laser therapy.

PMID- 22480696
TI  - Oculomotor assessments of executive function in preterm children.
AB  - OBJECTIVE: To use objective, nonverbal oculomotor tasks to assess executive
      function and infer the neural basis of impairments in preterm children. STUDY
      DESIGN: Cross-sectional study of preterm children age 9-16 years (n = 69; mean
      gestational age 29 weeks) and full-term controls (n = 43). Tasks assessed
      sensorimotor function (reflexive prosaccades); resistance to peripheral
      distracters (fixation); response inhibition, response preparation, and execution
      of a voluntary saccade (antisaccades); and spatial working memory (memory-guided
      saccades). Group differences were analyzed using ANOVA. We used linear regression
      to analyze the contributions of age, sex, gestational age, and white matter
      category to task performance. RESULTS: Preterm children did not differ from
      controls on basic sensorimotor function, response inhibition, and working memory.
      Compared with controls, preterm children showed greater susceptibility to
      peripheral distracters (P = .008) and were slower to initiate an inhibitory
      response (P = .003). Regression models showed contributions of age and white
      matter category to task performance. CONCLUSIONS: Preterm children show intact
      basic sensorimotor function and demonstrate difficulties in processes underlying
      executive control, including increased distractibility and prolonged response
      preparation. These limitations may reflect specific neural abnormalities in
      fronto-subcortical executive control of behavior.

PMID- 22480698
TI  - Fatal rhabdomyolysis in 2 children with LPIN1 mutations.
AB  - We report 2 cases of fatal rhabdomyolysis in children carrying an LPIN1 mutations
      preceded by similar electrocardiogram changes, including diffuse symmetrical high
      amplitude T waves. Our report underlines the severity of this disease and the
      need for active management of episodes of rhabdomyolysis in a pediatric intensive
      care unit.

PMID- 22480699
TI  - Longitudinal experiences of children remaining at home after a first-time
      investigation for suspected maltreatment.
AB  - OBJECTIVE: To describe longitudinal change in risk for children remaining at home
      following a first-time investigation for suspected maltreatment. STUDY DESIGN: A
      retrospective cohort study of children remaining at home following first-time
      investigation for maltreatment using a nationally representative sample of
      households involved with Child Protective Services. Outcomes include poverty,
      social support, caregiver depression, intimate partner violence (IPV),
      drug/alcohol dependence, corporal punishment, and child behavior problems at
      baseline, 18, and 36 months following first-time Child Protective Services
      investigation. We present longitudinal models to (1) estimate prevalence of risk
      factors at each timepoint; and (2) examine associations between risk-specific
      service referrals and longitudinal change in risk factor prevalence. RESULTS: Our
      sample represented 1057056 US children remaining at home following first-time
      investigation for maltreatment. Almost 100000 (9.2%) children experienced out-of
      home placement within 36 months. The prevalence of poverty (44.3%), poor social
      support (36.3%), caregiver depression (24.4%), IPV (22.1%), and internalizing
      (30.0%) and externalizing (35.8%) child behavior problems was above general
      population prevalence at baseline and remained high over the next 36 months.
      Referral to risk-specific services occurred in a minority of cases, but was
      associated with significant longitudinal reductions in IPV, drug/alcohol
      dependence, and externalizing child behavior problems. CONCLUSIONS: Children
      remaining at home following a first-time investigation for maltreatment live with
      persistent risk factors for repeat maltreatment. Appropriate service referrals
      are uncommon, but may be associated with meaningful reduction in risk over time.
      Pediatricians and policy makers may be able to improve outcomes in these families
      with appropriate service provision and referrals.

PMID- 22480700
TI  - Natural course and risk factors for persistence of IgE-mediated cow's milk
      allergy.
AB  - OBJECTIVE: To describe the natural course of IgE-mediated cow's milk allergy (IgE
      CMA) and to determine risk factors for its persistence in a population-based
      cohort. STUDY DESIGN: In a prospective cohort study, 54 infants with IgE-CMA were
      identified from a population of 13 019 children followed from birth. Diagnosis of
      IgE-CMA was based on history, skin prick test (SPT), and an oral food challenge
      (OFC) when indicated. Allergic infants were followed for 48-60 months. Families
      were contacted by telephone every 6 months and asked about recent exposures to
      milk. OFC was repeated to evaluate for recovery. Clinical characteristics, SPT,
      and OFC outcomes were compared between infants with persistent IgE-CMA and
      infants who recovered. RESULTS: Thirty-one infants (57.4%) recovered from IgE-CMA
      during the study period. Most infants (70.9%) recovered within the first 2 years.
      Risk factors for persistence on multivariate analysis included a reaction to <10
      mL of milk on OFC (or on first exposure as estimated by the guardian, if OFC was
      not performed) (P = .01), a larger wheal size on SPT (P = .014), and age of <=30
      days at time of first reaction (P = .05). CONCLUSIONS: Resolution occurs in most
      infants with IgE-CMA. Infants reacting to <10 mL of milk or in the first month of
      life, and those with a larger wheal size on SPT, are at increased risk for
      persistence.

PMID- 22480701
TI  - [Medication reconciliation? Prescription coordination is better].

PMID- 22480702
TI  - Metal biosorption onto dry biomass of Arthrospira (Spirulina) platensis and
      Chlorella vulgaris: multi-metal systems.
AB  - Binary and ternary systems of Ni(2+), Zn(2+), and Pb(2+) were investigated at
      initial metal concentrations of 0.5, 1.0 and 2.0mM as competitive adsorbates
      using Arthrospira platensis and Chlorella vulgaris as biosorbents. The
      experimental results were evaluated in terms of equilibrium sorption capacity and
      metal removal efficiency and fitted to the multi-component Langmuir and
      Freundlich isotherms. The pseudo second order model of Ho and McKay described
      well the adsorption kinetics, and the FT-IR spectroscopy confirmed metal binding
      to both biomasses. Ni(2+) and Zn(2+) interference on Pb(2+) sorption was lower
      than the contrary, likely due to biosorbent preference to Pb. In general, the
      higher the total initial metal concentration, the lower the adsorption capacity.
      The results of this study demonstrated that dry biomass of C. vulgaris behaved as
      better biosorbent than A. platensis and suggest its use as an effective
      alternative sorbent for metal removal from wastewater.

PMID- 22480703
TI  - Visible-light photocatalytic inactivation of Escherichia coli by K4Nb6O17 and
      Ag/Cu modified K4Nb6O17.
AB  - Ag/Cu modified K(4)Nb(6)O(17) thin film, a novel type of photocatalyst for
      photocatalytic inactivation of Escherichia coli under visible light irradiation
      was developed. The effects of loading method of Cu species on the characteristics
      of Ag-Cu nanocomposites and photocatalytic antibacterial activity were studied.
      Samples were characterized by powder X-ray diffraction (XRD), transmission
      electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and ultraviolet
      visible spectroscopy (UV-Vis). Irrespective of the preparation method, loading
      Ag, Cu and Ag-Cu composite as cocatalyst led to an increase in antibacterial
      activity as compared to bare K(4)Nb(6)O(17). In comparison with conventional
      impregnation method, well dispersed Ag-Cu nanocomposites were obtained on the
      K(4)Nb(6)O(17) surface by a sodium borohydride reduction method in the presence
      PVP. In this case, markedly improvement of photocatalytic activity was observed.
      The significant enhancement was ascribed to the high efficiency of electron hole
      pair separation related to the Ag-Cu nanocomposite on K(4)Nb(6)O(17) surface and
      the synergistic effects of coexisting Ag and Cu ions on antibacterial activity.

PMID- 22480704
TI  - Dissolution of explosive compounds TNT, RDX, and HMX under continuous flow
      conditions.
AB  - 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and
      octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) are common contaminants
      around active military firing ranges. Dissolution of these compounds is usually
      the first step prior to their spreading in subsurface environments. Nevertheless,
      dissolution of individual TNT, RDX, and HMX under continuous flow conditions has
      not been well investigated. This study applied spectral confocal microscopy to
      observe and quantify the dissolution of TNT, RDX, and HMX (<100 MUm crystals) in
      micromodel channels. Dissolution models were developed to describe the changes of
      their radii, surface areas, volumes, and specific surface areas as a function of
      time. Results indicated that a model incorporating a resistance term that
      accounts for the surface area in direct contact with the channel surfaces (and
      hence, was not exposed to the flowing water) described the dissolution processes
      well. The model without the resistance term, however, could not capture the
      observed data at the late stage of TNT dissolution. The model-fitted mass
      transfer coefficients were in agreement with the previous reports. The study
      highlights the importance of including the resistance term in the dissolution
      model and illustrates the utility of the newly developed spectral imaging method
      for quantification of mass transfer of TNT, RDX, and HMX.

PMID- 22480705
TI  - Acetaminophen degradation by electro-Fenton and photoelectro-Fenton using a
      double cathode electrochemical cell.
AB  - Acetaminophen is a widely used drug worldwide and is one of the most frequently
      detected in bodies of water making it a high priority trace pollutant. This study
      investigated the applicability of the electro-Fenton and photoelectro-Fenton
      processes using a double cathode electrochemical cell in the treatment of
      acetaminophen containing wastewater. The Box-Behnken design was used to determine
      the effects of initial Fe(2+) and H(2)O(2) concentrations and applied current
      density. Results showed that all parameters positively affected the degradation
      efficiency of acetaminophen with the initial Fe(2+) concentration being the most
      significant parameter for both processes. The acetaminophen removal efficiency
      for electro-Fenton was 98% and chemical oxygen demand (COD) removal of 43% while
      a 97% acetaminophen removal and 42% COD removal were observed for the
      photoelectro-Fenton method operated at optimum conditions. The electro-Fenton
      process was only able to obtain 19% total organic carbon (TOC) removal while the
      photoelectro-Fenton process obtained 20%. Due to negligible difference between
      the treatment efficiencies of the two processes, the electro-Fenton method was
      proven to be more economically advantageous. The models obtained from the study
      were applicable to a wide range of acetaminophen concentrations and can be used
      in scale-ups. Thirteen different types of intermediates were identified and a
      degradation pathway was proposed.

PMID- 22480706
TI  - Performance of sludge treatment wetlands using different plant species and porous
      media.
AB  - The aim of this study was to evaluate the dewatering and mineralisation
      efficiency of three sludge treatment wetlands (STW) configurations differing on
      plant species (Phragmites australis and Typha sp.) and filter medium (gravel and
      wood shavings). Sludge dewatering and mineralisation were monitored in three
      pilots STW for 2 years. The sludge volume was reduced by 80% in all
      configurations tested, the total solids (TS) increased to 16-24% TS and the
      volatile solids (VS) decreased to 50% VS/TS. After a resting period of three
      months the biosolids showed a high stabilisation (dynamic respiration index
      around 0.26-0.70 mgO(2)/gVS h), caused no phytotoxicity (germination index
      >100%), and had low heavy metals and pathogens concentrations (E. coli<240 MNP/g;
      absence of Salmonella). The lack of statistical significance (p>0.05) between the
      results obtained from the different STW configurations suggests that STW may be
      either planted with P. australis or Typha sp., and that wood shavings may replace
      gravel as filter medium.

PMID- 22480707
TI  - Stronger impact of dispersant plus crude oil on natural plankton assemblages in
      short-term marine mesocosms.
AB  - To assess the effects of crude oil and dispersant on marine planktonic
      ecosystems, analyses were performed in 1000-L mesocosm over a period of nine
      days. Triplicate experiments were conducted for two different treatments, namely,
      addition of crude oil alone and oil plus dispersant. In the mesocosm with oil
      plus dispersant, high concentrations of total petroleum hydrocarbon (TPH) were
      soon found in the bottom layer. In addition, most planktonic communities
      responded drastically to the presence of dispersant acting to disperse TPH: total
      bacterial abundances increased for the first two days and then decreased rapidly
      for the remainder of the experiment. The abundance of heterotrophic flagellates
      increased rapidly in association with the increase in bacterial cells. The
      abundance of phytoplankton and zooplankton communities decreased clearly within
      two days. Time-delayed relationship also revealed that the TPH concentration had
      a significant negative relationship with phyto- and zooplankton communities
      within two days. However, most planktonic communities were affected less
      adversely in the mesocosms treated with crude oil alone than in those treated
      with both crude oil and dispersant. The present results demonstrate that the
      planktonic ecosystem was damaged more severely by the introduction of dispersant
      than by the harmful effects of crude oil itself. Therefore, caution should be
      taken when considering the direct application of dispersant in natural
      environments, even though it has the advantage of rapidly removing crude oil.

PMID- 22480708
TI  - Aluminium salt slag characterization and utilization--a review.
AB  - Aluminium salt slag (also known as aluminium salt cake), which is produced by the
      secondary aluminium industry, is formed during aluminium scrap/dross melting and
      contains 15-30% aluminium oxide, 30-55% sodium chloride, 15-30% potassium
      chloride, 5-7% metallic aluminium and impurities (carbides, nitrides, sulphides
      and phosphides). Depending on the raw mix the amount of salt slag produced per
      tonne of secondary aluminium ranges from 200 to 500 kg. As salt slag has been
      classified as toxic and hazardous waste, it should be managed in compliance with
      the current legislation. Its landfill disposal is forbidden in most of the
      European countries and it should be recycled and processed in a proper way by
      taking the environmental impact into consideration. This paper presents a review
      of the aluminium salt slag chemical and mineralogical characteristics, as well as
      various processes for metal recovery, recycling of sodium and potassium chlorides
      content back to the smelting process and preparation of value added products from
      the final non metallic residue.

PMID- 22480709
TI  - Changes in Salix viminalis L. cv. 'Cannabina' morphology and physiology in
      response to nickel ions--hydroponic investigations.
AB  - The aim of the study was to assess the ability of 'basket willow' to
      bioaccumulate nickel with simultaneous analysis of biomass parameters and
      biomarkers of plants physiological reaction to the metal. Cuttings of Salix
      viminalis L. cv. 'Cannabina' were cultivated in Knop's medium containing nickel
      at 0-3mM stabilized with quartz sand. Higher nickel contents were observed in
      Salix rods and roots (~15), and lower for leaves and shoots (~3 mg kg(-1)DW)
      after 14 days at 3 mM Ni. The strongest inhibition was observed for root biomass,
      weaker for shoot, root and leaf elongation, and the weakest for the
      photosynthetic area (4, 24, 36, 55 and 70% of control, respectively). Soluble
      carbohydrates in leaves reached 340% of control at 3.0mM Ni. Phenolics content
      increased four-fold at 3mM Ni versus control, while salicylic acid content at 2.5
      mM Ni was nearly 68 times higher than for Ni-untreated plants. The exudation of
      low molecular weight organic acids increased from ~40 to 130 MUM kg(-1)DW at 3
      mM. The investigated cultivar exhibits sufficient resistance to nickel and can be
      cultivated at heavily contaminated sites. Nevertheless, strong inhibition of
      plant growth was observed resulting probably from Ni-induced disturbances in
      nutrient uptake accompanied by oxidative stress.

PMID- 22480710
TI  - Distribution, source identification, and historical trends of organic
      micropollutants in coastal sediment in Jakarta Bay, Indonesia.
AB  - We determined concentrations of polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyls (PCBs), linear alkylbenzenes (LABs), and hopanes in
      coastal sediments collected from Jakarta Bay and Tokyo Bay. PAH concentrations in
      sediments from Jakarta Bay (257-1511 ng/g-dry) were lower than or comparable to
      those from Tokyo Bay (1372-1615 ng/g-dry). Ratios of alkyl-PAHs to parent PAHs
      showed a greater contribution of petrogenic inputs in Jakarta Bay than in Tokyo
      Bay. This difference is consistent with the higher ratio of hopanes to PAHs in
      Jakarta Bay. LAB concentrations in Jakarta Bay (geometric mean, 1400 ng/g-dry)
      were higher than those in Tokyo Bay (661 ng/g-dry). The internal to external
      (I/E) ratios of LABs in Jakarta Bay (0.92-2.88) were lower than those in Tokyo
      Bay (2.8-4.8), indicating that Jakarta Bay receives untreated or poorly treated
      sewage. Significant amounts of tetrapropylene-based alkylbenzenes were detected
      in several locations in Jakarta Bay, suggesting current usage of the non
      degradable surfactants alkylbenzene sulfonates that are banned in many countries.
      The PCB concentration in Jakarta Bay was 1 order of magnitude lower than in Tokyo
      Bay, suggesting minimal usage of PCBs in industrial or commercial products in
      Jakarta. Analyses of a sediment core indicate increasing inputs of PAHs, hopanes,
      and LABs into Jakarta Bay during recent decades.

PMID- 22480712
TI  - Unemployment and suicide in the Stockholm population: a register-based study on
      771,068 men and women.
AB  - OBJECTIVES: Several studies have reported a higher risk of suicide among the
      unemployed. Some individuals may be more prone to both unemployment and suicide
      due to an underlying health-related factor. In that case, suicide among the
      unemployed might be a consequence of health-related selection. This study aimed
      to investigate the relationship between unemployment and suicide, and the
      importance of previous sickness absence to this relationship. STUDY DESIGN: The
      study was based on 771,068 adults aged 25-58 years in Stockholm County in 1990
      1991. Data on sickness absence in 1990-1991 and unemployment in 1991-1993 were
      collected from registers for each individual. Time and cause of death in 1994
      1995 were obtained from Sweden's Cause of Death Register. METHODS: The
      association between sickness absence in 1990-1991 and unemployment in 1992-1993,
      and the association between unemployment in 1992-1993 and suicide in 1994-1995
      was investigated using logistic regression. RESULTS: Unemployment lasting for >90
      days in 1992-1993 was associated with suicide in men in 1994-1995 [odds ratio
      (OR) 2.16, 95% confidence interval (CI) 1.38-3.38], while unemployment lasting
      for <= 90 days in 1992-1993 was associated with suicide in women in 1994-1995 (OR
      2.68, 95% CI 1.23-5.85). Higher levels of sickness absence were related to an
      increased risk of subsequent unemployment in both sexes. The higher prevalence of
      sickness absence among the unemployed attenuated the association between
      unemployment and suicide in both men and women. CONCLUSIONS: Unemployment is
      related to suicide. Individuals in poor health are at increased risk of
      unemployment and also suicide. The higher relative risk of suicide among the
      unemployed seems to be, in part, a consequence of exclusion of less healthy
      individuals from the labour market.

PMID- 22480713
TI  - Shipyards and sectarianism: how do mortality and deprivation compare in Glasgow
      and Belfast?
AB  - BACKGROUND: The extent to which the higher level of mortality seen in Glasgow
      compared with other UK cities is solely attributable to socio-economic
      deprivation has been the focus of much discussion recently. Some authors have
      suggested that poorer health in the city may be influenced by issues related to
      its history of religious sectarianism. In order to investigate this further, this
      study compared deprivation and mortality between Glasgow and Belfast, a similar
      post-industrial city, but one with a considerably more pronounced sectarian
      divide. OBJECTIVES: To compare the deprivation and mortality profiles of the two
      cities; to assess the extent to which any differences in mortality can be
      explained by differences in area-based measures of deprivation; and to examine
      whether these analyses shed any light on the 'sectarianism' hypothesis for
      Glasgow's excess mortality relative to elsewhere in the UK. STUDY DESIGN AND
      METHODS: Replicating the methodology of a recent study comparing deprivation and
      mortality in Glasgow, Liverpool and Manchester, rates of 'income deprivation' for
      2005 were calculated for every small area across the two cities (average
      population size: 1810 in Belfast; 1650 in Glasgow). Standardized mortality ratios
      were calculated for the period 2003-2007 for Glasgow relative to Belfast,
      standardizing for age, gender and income deprivation decile. RESULTS: While total
      levels of deprivation were slightly higher in Glasgow than in Belfast (24.8% of
      Glasgow's population were income deprived in 2005 compared with 22.4% in
      Belfast), Belfast was more unequal in terms of its distribution of deprivation
      across the city. After standardizing for age, sex and deprivation, all-cause
      mortality in Glasgow was 27% higher for deaths under 65 years of age and 18%
      higher for deaths at all ages. Higher all-cause mortality in Glasgow was shown in
      the majority of sub-analyses (i.e. for most age groups, both sexes and across the
      majority of deprivation deciles). Analyses of particular causes of death showed
      significantly higher mortality in Glasgow relative to Belfast for all conditions
      examined except 'external causes'. Notably higher mortality was evident for drug
      related poisonings and alcohol-related causes among men in both cities. With a
      small number of exceptions, the results were very similar to those shown for
      Glasgow in comparison with Liverpool and Manchester. CONCLUSIONS: Area-based
      deprivation did not explain the higher mortality in Glasgow in comparison with
      Belfast. Belfast has a more profound history of sectarianism, and similar
      climatic conditions, to Glasgow. If these factors were to be important in
      explaining the high mortality in Glasgow, the question arises as to why they have
      not produced similar effects in Belfast.

PMID- 22480714
TI  - Informal waste management system in Nigeria and barriers to an inclusive modern
      waste management system: a review.
AB  - OBJECTIVES: To explore the activities of the informal waste management sector in
      Nigeria, and barriers to integrating them in an inclusive waste management
      system. STUDY DESIGN: Literature review. METHODS: A literature review was
      undertaken to evaluate the informal waste management system and formal waste
      management system in Nigeria and other developing countries with similar
      settings. Nine databases were searched and 34 studies met the following inclusion
      criteria: evaluation of the role of informal waste collectors, recycling and
      solid waste management in developing countries. RESULTS: Most of the evaluated
      studies (97%, n = 33) acknowledged the significant environmental and socio
      economic roles played by the informal waste collectors and scavengers in
      developing countries. The studies identified the following as barriers to
      inclusive waste management in Nigeria: repressive policy, unhygienic waste
      collection methods, lack of evidence to support activity, and low quality and
      quantity of secondary materials. CONCLUSIONS: Scavengers and other groups of
      informal recyclers see waste as a source of income and livelihood, whilst the
      general public see it as an aesthetic problem and see the people engaged in
      resource recovery as a social nuisance. Integrating their informal services with
      the formal waste management system is a potential tool to empower these people to
      increase their skills in resource recovery and improve their working and living
      conditions. Inclusive waste management is a process, and observable changes are
      taking place in some developing countries where waste pickers and informal waste
      collectors have become environmental agents. A major limitation to the
      integration of informal waste collectors and scavengers is the social acceptance
      of their activity as a viable source of income, and of themselves as
      environmental agents in the sustainability of virgin resources.

PMID- 22480715
TI  - Reliability and validity of the PDS and PSS-I among participants with PTSD and
      alcohol dependence.
AB  - The prevalence of alcohol use disorder (e.g., alcohol dependence; AD) among
      individuals with posttraumatic stress disorder (PTSD) is quite high, with
      estimates of 52% for men and 30% for women (Kessler, Sonnega, Bromet, Hughes, &
      Nelson, 1995). There are several interviews and self-report measures of PTSD with
      good published psychometric properties, and they are routinely used with comorbid
      AD and PTSD. However, none of these instruments was validated with this
      population. The current study fills this gap by examining the psychometric
      properties of the PTSD Symptom Scale-Interview (PSS-I) and the self-report PTSD
      Diagnostic Scale (PDS) in individuals diagnosed with current PTSD and AD. Both
      scales comprised of 17 items provide diagnostic and symptom severity information
      according to DSM-IV-TR criteria. Participants were 167 individuals who were
      diagnosed with AD and chronic PTSD and were enrolled in a randomized controlled
      treatment study. Results revealed excellent internal consistency of both the PSS
      I and the PDS, good test-retest reliability over a 1-month period, and good
      convergent validity with the SCID. The specificity of the PSS-I diagnosis of PTSD
      was better than the PDS diagnosis, the latter exhibiting a greater percentage of
      false positives. In sum, the results showed that the PSS-I and PDS performed well
      in this population and can be used with confidence to assess PTSD diagnosis and
      symptom severity.

PMID- 22480717
TI  - The arginine kinase in Zhikong scallop Chlamys farreri is involved in
      immunomodulation.
AB  - Arginine kinase (AK) catalyzes the reversible phosphorylation of l-arginine to
      form phosphoarginine, and plays a critical role in energy metabolism in
      invertebrates. In the present study, a scallop AK gene was identified from
      Chlamys farreri with an open reading frame (ORF) of 1101bp encoding for a protein
      of 366 amino acids (designed as CfAK). An ATP-gua PtransN domain which was
      described as a guanidine substrate specificity domain (GS domain) and an ATP-gua
      Ptrans domian which was responsible for binding ATP, were both identified in
      CfAK. The mRNA transcripts of CfAK were detectable in haemocytes, hepatopancreas,
      adductor muscle, mantle, gill, kidney and gonad, with the highest expression
      level in the muscle and the lowest level in the hemocytes. The expression level
      of CfAK mRNA increased from fertilized eggs to eyebot, and reached the highest in
      the trochophore stage. The relative expression level of CfAK mRNA in muscle was
      up-regulated significantly after LPS (0.5mg/mL) stimulation, and reached the peak
      at 6h (5.2-fold, P<0.05). The activity of inducible nitric oxide synthase (iNOS)
      in the supernatant of muscle homogenate increased significantly from 3.2U/mg at 0
      h to 9.7 U/mg at 12h after LPS stimulation, while the concentration of nitric
      oxide (NO) in the supernatant of muscle homogenate began to increase at 3h (21.55
      MUmol/L), and reached the top concentration at 24h (42.27 MUmol/L), then
      recovered to the normal level after 48 h. The recombinant protein of CfAK (rCfAK)
      expressed in Escherichia coli displayed Arginine kinase activity, and its
      apparent K(m) was 0.82 +/- 0.11 and 1.24 +/- 0.13 mM for L-arginine and ATP-Na,
      respectively. The results indicated that the CfAK was involved in energy
      production and utilization during the whole life process, and might refer to the
      immunomodulation process via altering the NO concentration and iNOS activity in
      scallop Chlamys farreri.

PMID- 22480716
TI  - Personality and the latent structure of PTSD comorbidity.
AB  - This study examined the structure of PTSD comorbidity and its relationship to
      personality in a sample of 214 veterans using data from diagnostic interviews and
      the Multidimensional Personality Questionnaire-Brief Form (MPQ-BF; Patrick,
      Curtin, & Tellegen, 2002). Confirmatory factor analyses supported a three factor
      model composed of Externalizing, Fear and Distress factors. Analyses that
      examined the location of borderline personality disorder revealed significant
      cross-loadings for this disorder on both Externalizing and Distress. Structural
      equation models showed trait negative emotionality to be significantly related to
      all three comorbidity factors whereas positive emotionality and constraint
      evidenced specific associations with Distress and Externalizing, respectively.
      These results shed new light on the location of borderline personality disorder
      within the internalizing/externalizing model and clarify the relative influence
      of broad dimensions of personality on patterns of comorbidity.

PMID- 22480718
TI  - Effect of luteinizing hormone on the right regressing ovary of newly hatched
      chicks treated during embryonic development.
AB  - We studied the histologic and stereological changes induced in the right ovary of
      newly hatched chicks treated with LH during their embryonic development. Results
      indicate that LH administration causes a diminution in size and total volume (P <
      0.01) of the right ovary, as well as a decrease in the total volume of lacunar
      channels, blood vessels, and interstitium. Other changes obtained after LH
      treatment were a reduction (P < 0.001) in the number of germ cells, as well as an
      increase in the total volume of interstitial cell cords (P < 0.01). This
      expansion is due to the increase of cellular volume of interstitial cells (P <
      0.001) and not to their number, which decrease in the LH-treated right ovary. All
      these modifications were similar to those occurring in the regressing right ovary
      during development. The findings suggest that the right ovary of the newly
      hatched chick is able to respond to LH treatment during embryonic development,
      inducing marked histologic changes that accelerate its regression.

PMID- 22480719
TI  - Energy metabolism in the newborn farm animal with emphasis on the calf: endocrine
      changes and responses to milk-born and systemic hormones.
AB  - Neonatal mammals need adaption to changes in nutrient supply because energy
      intake shifts from continuous parenteral supply of nutrients (mainly glucose,
      lactate, and amino acids) via the placenta to discontinuous colostrum and milk
      intake with lactose and fat as main energy sources. Besides ingested lactose,
      endogenous glucose production is essential in the neonate to assure sufficient
      glucose availability. Fetal endogenous glucose production is low, but endocrine
      changes (especially the prenatal rise of glucocorticoid production) promote
      maturation of metabolic pathways that enable marked glycogen synthesis before and
      enhanced gluconeogenesis after birth to establish an adequate glucose status
      during postnatal maturation. In preterm born farm animals gluconeogenic activity
      is low, mainly because of a low glucocorticoid and thyroid status. In full-term
      neonates, endogenous glucose production increases with age. Colostral bioactive
      components (such as growth factors, hormones, bioactive peptides, and cytokines)
      do not have a direct effect on endogenous glucose production. However, colostrum
      feeding stimulates intestinal growth and development, an effect at least in part
      mediated by bioactive substances. Increased nutrient and glucose absorption thus
      allows increased glucose supply and hepatic glycogen storage, which improves the
      glucose status. The improved energetic status of colostrum-fed neonates is
      reflected by an accelerated maturation of the somatotropic axis, leading
      especially to enhanced production of IGF-I in the neonate. Secretion and
      production of hormones involved in the regulation of glucose and fat metabolism
      in neonates depend on the developmental stage and the response to feeding. In
      addition, many such hormones have actions in the neonate that differ from adult
      animals. Endocrine action to support endogenous energy supply in neonates is
      probably not fully established, and therefore, needs postnatal maturation.
      Therefore, our knowledge on energy metabolism in the neonate needs to be extended
      to better understand the function and the failure and to assess endocrine
      responses during the neonatal period.

PMID- 22480720
TI  - Cytokine release from human leukocytes exposed to silorane- and methacrylate
      based dental materials.
AB  - OBJECTIVES: Silorane-based dental monomers contain an epoxy functional group.
      Less is known about the toxicological and inflammatory potential of silorane
      based composites. Therefore we compared the release of 24 cytokines from human
      leukocytes after incubation with silorane-based FiltekTM Silorane (Silo) and
      methacrylate-based TetricEvo Flow(r) (TC). METHODS: Leukocytes from nine healthy
      test persons (P) were incubated with Silo or TC for up to 72h. All 24h cytokines
      were quantified with a magnetic bead assay. RESULTS: Silo stimulates the
      leukocytes to higher release of cytokines when compared to TC. 72h after
      beginning the experiment, leukocytes from P6 incubated with Silo secreted more
      than an 18-fold amount of interleukin (IL)-6 when compared with leukocytes
      incubated with TC (771.8 vs 42.1pg/ml). Only leukocytes from P8 incubated with
      Silo release up to 14.4pg/ml IL-2 after 72h. SIGNIFICANCE: The significantly
      higher induction of cytokines with Silo in comparison to TC is test person
      independent. This indicates a higher sensitization potential for Silo. Because of
      the cytokine release pattern (especially the release of T-cell dependent IL-2)
      from leukocytes from P8 after incubation with Silo it is likely that P8 can
      develop an allergic Type IV sensitization to Silo. Therefore the cytokine release
      assay is a helpful tool for providing information about possible immunological
      reactions to dental resins in individual cases as well as for a general risk
      assessment and comparison between different dental materials.

PMID- 22480721
TI  - A comparative study between crack analysis and a mechanical test for assessing
      the polymerization stress of restorative composites.
AB  - OBJECTIVES: To verify the hypothesis that crack analysis and a mechanical test
      would rank a series of composites in a similar order with respect to
      polymerization stress. Also, both tests would show similar relationships between
      stress and composite elastic modulus and/or shrinkage. METHODS: Soda-lime glass
      discs (2-mm thick) with a central perforation (3.5-mm diameter) received four
      Vickers indentations 500 MUm from the cavity margin. The indent cracks were
      measured (500*) prior and 10 min after the cavity was restored with one of six
      materials (Kalore/KL, Gradia/GR, Ice/IC, Wave/WV, Majesty Flow/MF, and Majesty
      Posterior/MP). Stresses at the indent site were calculated based on glass
      fracture toughness and increase in crack length. Stress at the bonded interface
      was calculated using the equation for an internally pressurized cylinder. The
      mechanical test used a universal testing machine and glass rods (5-mm diameter)
      as substrate. An extensometer monitored specimen height (2mm). Nominal stress was
      calculated dividing the maximum shrinkage force by the specimen cross-sectional
      area. Composite elastic modulus was determined by nanoindentation and post-gel
      shrinkage was measured using strain gages. Data were subjected to one-way
      ANOVA/Tukey or Kruskal-Wallis/Mann-Whitney tests (alpha: 5%). RESULTS: Both tests
      grouped the composites in three statistical subsets, with small differences in
      overlapping between the intermediate subset (MF, WV) and the highest (MP, IC) or
      the lowest stress materials (KL, GR). Higher stresses were developed by
      composites with high modulus and/or high shrinkage. SIGNIFICANCE: Crack analysis
      demonstrated to be as effective as the mechanical test to rank composites
      regarding polymerization stress.

PMID- 22480722
TI  - Water sorption characteristics of restorative dental composites immersed in
      acidic drinks.
AB  - OBJECTIVES: To determine the diffusion coefficient, water sorption and solubility
      of various types of restorative dental composites and to evaluate the effect of
      acidic media (orange juice and coke) on their characteristics. METHODS: Resin
      composite specimens (FiltekTM Z350, Spectrum((r)) TPH((r))3 and Durafill((r)) VS)
      were prepared in a stainless steel mold of 1mm thickness and 10mm diameter (n=5)
      and light-cured. All samples were dried at 37 degrees C, immersed in media
      (distilled water, orange and coke) at 37 degrees C and weighed at suitable time
      intervals (15, 35, 155, 320, 785, etc.min) until 40 days of immersion and then
      were dried again for 40 days. Diffusion coefficient (m(2)s(-1)) was determined
      according to Fick's second law while water sorption and solubility (MUg/mm(3))
      were calculated based on BS EN ISO 4049:2000. Data of water sorption and
      solubility were analyzed with One-Way ANOVA and post hoc Scheffe test at p=0.05.
      RESULTS: The experimental data obtained were obeyed and nearly fitted to the
      diffusion theoretical data plot. The highest values of diffusion coefficients
      were presented by Durafill((r)) VS (32.23-45.25*10(-13)m(2)s(-1)). Diffusion
      coefficients of FiltekTM Z350 and Spectrum((r)) TPH((r))3 were the highest when
      immersed in coke media followed by distilled water and orange juice. The water
      sorption of most composites was significantly increased after immersion in coke
      and orange (p<0.05). Meanwhile only Spectrum((r)) TPH((r))3 showed an increase in
      solubility when immersed in coke media. Z350 presented the highest water sorption
      after immersion in distilled water and coke (16.13 and 18.22MUg/mm(3)) while
      Durafill((r)) VS presented the highest solubility (7.20-9.27MUg/mm(3)).
      SIGNIFICANCE: The exposure of restorative dental composites to acidic drinks can
      cause an increase in diffusion coefficient, water sorption and solubility
      parameters which may accelerate the degradation process and thus reduce the life
      span of composite restoration.

PMID- 22480723
TI  - [IgG4-related disease and renal and urological involvement].
AB  - Hyper-IgG4 syndrome, or IgG4-related disease, is an emerging disorder, involving
      one or more organ(s), and characterized by "storiform" fibrosis and inflammatory
      lesions with a predominance of IgG4+ plasma cells and increased IgG4 serum
      levels. Since the first report of auto-immune pancreatitis, numerous organ
      lesions have been reported and have been found to occur in a same patient
      including: sialadenitis, dacryoadenitis, lymphadenopathy, liver and biliary tract
      involvement, and renal and retroperitoneal lesions. Renal involvement was first
      described in 2004 and usually presents as functional and/or morphological
      abnormalities. In most cases, renal pathological analysis reveals
      tubulointerstitial nephritis that is rarely associated with glomerular lesions.
      Retroperitoneal fibrosis is also a typical feature that may be associated with
      periaortitis or inflammatory abdominal aortic aneurysm. First line treatment is
      based on corticosteroid therapy. Short-term outcome is usually favorable.
      However, patients should be carefully monitored for relapses and long-term
      complications. Although the multiple organ lesions share common clinical,
      biological, radiological and pathological features, no consensus diagnostic
      criteria have yet been validated for IgG4-related disease. Ruling out
      differential diagnoses is thus mandatory. Our literature review provides
      nephrologists, urologists and pathologists with key elements that will help in
      the early diagnosis and proper management of this new and emerging disorder.

PMID- 22480724
TI  - Get the signal to reduce the noise of pharmacological 'toys'.

PMID- 22480725
TI  - Long-term treatment, tolerability, and survival with sub-cutaneous treprostinil
      for severe pulmonary hypertension.
AB  - BACKGROUND: Randomized controlled trials have resulted in improved outcomes in
      pulmonary arterial hypertension; however, they are biased by stringent inclusion
      criteria, pre-specified patient sub-sets, and study durations. In addition,
      common practice is to start oral therapies ahead of the more potent and
      titratable prostanoid therapies, despite advanced disease states at diagnosis.
      The objectives of our prospective registry were to evaluate long-term effects on
      functional class, 6-minute walking distance, hemodynamics, and survival, and also
      long-term tolerability of first-line sub-cutaneous treprostinil, a prostacyclin
      analog, in patients with severe pulmonary hypertension. METHODS: Data were
      collected from patients with functional class III/IV pre-capillary pulmonary
      hypertension (Dana Point groups 1 and 4; mean right arterial pressure >= 10 mmHg,
      and/or cardiac index <= 2.2 liters/min/m(2)). Treprostinil dose adjustments were
      driven by clinical symptoms and side effects. RESULTS: The study included 111
      patients (1999 to 2010). Of these, 13 (12%) stopped treatment prematurely because
      of drug side effects, 11 (9.9%) underwent double lung transplantation, and 49
      (44.1%) died of any cause (41 on treatment, 8 after early drug discontinuation).
      Overall survival rates at 1, 5, and 9 years were 84%, 53%, and 33%. In patients
      who were able to tolerate treatment > 6 months, survival rates were 57% at 9
      years. CONCLUSION: First-line treatment of severe pre-capillary pulmonary
      hypertension with sub-cutaneous treprostinil is safe and efficacious over many
      years. If up-titration beyond 6 months is tolerated, effective doses are reached
      and outcomes are good.

PMID- 22480726
TI  - Odor compounds from different sources of landfill: characterization and source
      identification.
AB  - This study investigated the odor compounds from different areas in a landfill
      site, which included the municipal solid waste (MSW)-related area, the leachate
      related area and the sludge-related area. Nine sampling points were placed and 35
      types of odorous substances were measured and quantified from these grabbed
      samples. The results showed that the main odorous substances emitted from
      landfill site were styrene, toluene, xylene, acetone, methanol, n-butanone, n
      butylaldehyde, acetic acid, dimethyl sulfide, dimethyl disulfide and ammonia. In
      the MSW-related area, the highest concentrations of oxygenated compounds were
      observed at the gas extraction wells (GW), while sulfur compounds were rare.
      Ammonia in the sludge-related area was very abundant. Sludge discharge area (SD1)
      and sludge disposal work place (SD2) were representative points of pre- and post
      drying, in which the characterizations of the emitted odorous gas were different.
      After chemical drying, the concentration of ammonia increased, whereas those of
      volatile fatty acids and sulfur compounds decreased. In the leachate-related
      area, relatively low concentrations of all those odorants were detected in
      leachate storage pool (LS), which may be due to the enclosure operation of the
      leachate storage pool. Using principal components analysis and cluster analysis,
      GW, SD1 and SD2 were distinguished from the other sampling points. The typical
      odorants in GW were acetaldehyde, ethyl benzene, xylene, methylamine and dimethyl
      formamide. The typical odorants in SD1 were methyl mercaptan, valeric acid and
      isovaleric acid, while those in SD2 were carbon disulfide, acetone, 3-pentanone,
      methanol and trimethylamine. The typical odorants in other sampling points were
      hydrogen sulfide, n-butylaldehyde and acetic acid.

PMID- 22480727
TI  - Degradation and environmental risk of surfactants after the application of
      compost sludge to the soil.
AB  - In this work, the degradation of anionic and non-ionic surfactants in
      agricultural soil amended with sewage sludge is reported. The compounds analysed
      were: linear alkylbenzene sulphonates (LAS) with a 10-13 carbon alkylic chain,
      and nonylphenolic compounds (NPE), including nonylphenol (NP) and nonylphenol
      ethoxylates with one and two ethoxy groups (NP1EO and NP2EO). The degradation
      studies were carried out under winter (12.7 degrees C) and summer (22.4 degrees
      C) conditions in Andalusia region. The concentration of LAS was reduced to 2% of
      the initial concentration 100 day after sludge-application to the soil. The half
      life time measured for LAS homologues were ranged between 4 and 14days at 12.7
      degrees C and between 4 and 7 days at 22.4 degrees C. With regard to NPE
      compounds, after 8 and 4days from the beginning of the experiment at 12.7 and
      22.4 degrees C, respectively, their concentration levels were increased to 6.5
      and 13.5mg/kgdm (dry matter) as consequence of the degradation of nonylphenol
      polyethoxylates. These concentration levels were reduced to 5% after 63 and 70
      days for 12.7 degrees C and 22.4 degrees C, respectively. The half-life times
      measured for NPEs were from 8 to 16 days at 12.7 degrees C and from 8 to 18 days
      at 22.4 degrees C. Environmental risk assessment revealed that for LAS homologues
      no environment risk could be expected after 7 and 8 days of sludge application to
      the soil for 22.4 and 12.7 degrees C, respectively; however, potential toxic
      effects could be observed for the nonylphenolic compounds during the first 56
      days after sludge application to the soil.

PMID- 22480728
TI  - Elevated brain iron is independent from atrophy in Huntington's Disease.
AB  - Increased iron in subcortical structures in patients with Huntington's Disease
      (HD) has been suggested as a causal factor of neuronal degeneration. The present
      study examines iron accumulation, measured using magnetic resonance imaging
      (MRI), in premanifest gene carriers and in early HD patients as compared to
      healthy controls. In total 27 early HD patients, 22 premanifest gene carriers and
      25 healthy controls, from the Leiden site of the TRACK-HD study, underwent 3T MRI
      including high resolution 3D T(1)- and T(2)-weighted and asymmetric spin echo
      (ASE) sequences. Magnetic Field Correlation (MFC) maps of iron levels were
      constructed to assess magnetic field inhomogeneities and compared between groups
      in the caudate nucleus, putamen, globus pallidus, hippocampus, amygdala,
      accumbens nucleus, and thalamus. Subsequently the relationship of MFC value to
      volumetric data and disease state was examined. Higher MFC values were found in
      the caudate nucleus (p<0.05) and putamen (p<0.005) of early HD compared to
      controls and premanifest gene carriers. No differences in MFC were found between
      premanifest gene carriers and controls. MFC in the caudate nucleus and putamen is
      a predictor of disease state in HD. No correlation was found between the MFC
      value and volume of these subcortical structures. We conclude that Huntington's
      disease patients in the early stages of the disease, but not premanifest gene
      carriers, have higher iron concentrations in the caudate nucleus and putamen. We
      have demonstrated that the iron content of these structures relates to disease
      state in gene carriers, independently of the measured volume of these structures.

PMID- 22480729
TI  - Distinct role of spatial frequency in dissociative reading of ideograms and
      phonograms: an fMRI study.
AB  - It has been proposed that distinct neural circuits are activated by reading
      Japanese ideograms (Kanji) and phonograms (Kana). By measuring high-density event
      related potentials, we recently reported that spatial frequency (SF) information
      is responsible for the dissociation between Kanji and Kana reading. In
      particular, we found close links between Kana and low SF (LSF) information and
      between Kanji and high SF (HSF) information. However, it remains unclear which
      brain regions contribute to this dissociation. To determine this, we performed
      functional magnetic resonance imaging while presenting unfiltered or spatially
      filtered Kanji and Kana word stimuli to healthy native Japanese subjects. Fourier
      analysis revealed that Kanji and Kana stimuli were characterized by HSF and LSF
      information, respectively. When presented with either type of unfiltered stimulus
      (Kanji or Kana), the bilateral inferior temporal (IT, BA 37) regions were
      activated compared to the resting condition. Kana but not Kanji reading also
      activated the bilateral inferior parietal lobules (IPL, BA 40). When we compared
      Kanji and Kana reading directly, the left IT region was significantly activated
      by Kanji reading, while significant activation of the left IPL was observed
      during Kana reading. In response to filtered HSF stimuli, the Kanji reading minus
      Kana reading comparison revealed significant activation of the left IT region but
      not the left IPL. Conversely, significant activation of the left IPL but not the
      left IT region occurred in the Kana reading minus Kanji reading comparison for
      filtered LSF stimuli. These results suggest that Kanji and Kana engage a
      relatively overlapping network, within which the left IT is more involved in
      Kanji processing, while the left IPL contributes more to Kana processing. The
      preferential engagements of these brain regions could reflect the close links
      between Kana and LSF information, and between Kanji and HSF information.
      Therefore, this study provides further evidence that SF contributes to the
      dissociation between Kanji and Kana reading.

PMID- 22480731
TI  - The spliceosome: a flexible, reversible macromolecular machine.
AB  - With more than a hundred individual RNA and protein parts and a highly dynamic
      assembly and disassembly pathway, the spliceosome is arguably the most
      complicated macromolecular machine in the eukaryotic cell. This complexity has
      made kinetic and mechanistic analysis of splicing incredibly challenging. Yet,
      recent technological advances are now providing tools for understanding this
      process in much greater detail. Ranging from genome-wide analyses of splicing and
      creation of an orthogonal spliceosome in vivo, to purification of active
      spliceosomes and observation of single molecules in vitro, such new experimental
      approaches are yielding significant insight into the inner workings of this
      remarkable machine. These experiments are rewriting the textbooks, with a new
      picture emerging of a dynamic, malleable machine heavily influenced by the
      identity of its pre-mRNA substrate.

PMID- 22480730
TI  - Gene delivery to bone.
AB  - Gene delivery to bone is useful both as an experimental tool and as a potential
      therapeutic strategy. Among its advantages over protein delivery are the
      potential for directed, sustained and regulated expression of authentically
      processed, nascent proteins. Although no clinical trials have been initiated,
      there is a substantial pre-clinical literature documenting the successful
      transfer of genes to bone, and their intraosseous expression. Recombinant vectors
      derived from adenovirus, retrovirus and lentivirus, as well as non-viral vectors,
      have been used for this purpose. Both ex vivo and in vivo strategies, including
      gene-activated matrices, have been explored. Ex vivo delivery has often employed
      mesenchymal stem cells (MSCs), partly because of their ability to differentiate
      into osteoblasts. MSCs also have the potential to home to bone after systemic
      administration, which could serve as a useful way to deliver transgenes in a
      disseminated fashion for the treatment of diseases affecting the whole skeleton,
      such as osteoporosis or osteogenesis imperfecta. Local delivery of osteogenic
      transgenes, particularly those encoding bone morphogenetic proteins, has shown
      great promise in a number of applications where it is necessary to regenerate
      bone. These include healing large segmental defects in long bones and the
      cranium, as well as spinal fusion and treating avascular necrosis.

PMID- 22480732
TI  - The parental brain: transformations and adaptations.
AB  - Few evolutionary transformations rival the complex neurobiological modifications
      accompanying the mammalian transition to parenthood. Research conducted primarily
      in maternal rodents highlights the engagement of multiple areas of the brain to
      initiate and maintain interest in resource-depleting vulnerable pups throughout
      lactation. Interestingly, many modifications marking the transition to motherhood
      result in adaptive response options that persist well beyond the weaning of pups;
      specifically, adaptations such as cognitive flexibility, emotional regulation and
      enhanced social attentiveness coincide with the parenthood transition and have
      emerged as defining characteristics of the most adaptive mammalian species. The
      paternal brain also results in interesting modifications that, in some biparental
      species, mimic the effects observed in females. Taken together, research suggests
      that the designation of "parent" is less of a categorical variable and more of a
      continuous variable, with the quality of nurturing responses directed toward
      offspring influenced by many factors such as predisposed sensitivity to
      reproductive hormones, nature and duration of exposure to offspring, number of
      reproductive experiences, adequate resources, and composition of the social
      environment. Indeed, the transition from an animal focused on self-preservation
      to one that is responsive to the needs of other animals, and the accompanying
      increases in reproductive fitness, represent a significant evolutionary
      transition, or upgrade of sorts, leading to a more diverse array of response
      options to meet the challenging demands of changing environmental and social
      terrains.

PMID- 22480734
TI  - Signal transduction pathway activity compensates dopamine D2/D3 receptor density
      changes in Parkinson's disease: a preliminary comparative human brain receptor
      autoradiography study with [3H]raclopride and [35S]GTPgammaS.
AB  - The degeneration of dopaminergic nigrostriatal pathway in Parkinson's disease
      (PD) results in alterations of the dopamine receptor system. In the present study
      we have investigated the relationship between the disease related changes of
      expressed dopamine D2/D3 receptor density and the corresponding intracellular
      signal transduction route in cortical and sub-cortical brain structures in the
      human brain. Dopamine D2/D3 receptor autoradiography (ARG), using [3H]raclopride,
      and agonist stimulated [35S]GTPgammaS (guanosine 5'-O-[gamma-thio]triphosphate)
      binding autoradiography have been performed in human striatum, cingulate gyrus
      and medial frontal gyrus samples obtained from six deceased PD patients and six
      age matched control subjects. Receptor densities were expressed as fmol/gram
      tissue protein for [3H]raclopride; agonist stimulated [35S]GTPgammaS binding was
      expressed in fmol/gram tissue and its change was expressed in percentage values
      above basal binding. Our results indicate that whereas there is a decrease of the
      dopamine D2/D3 receptors in the striatum demonstrated by classical receptor
      autoradiography (controls and PD: 24.08+/-2.06 fmol/gram (mean+/-SEM) and 18.43+/
      2.82 fmol/gram, respectively; p<0.05), the corresponding agonist stimulated
      [35S]GTPgammaS binding autoradiography shows unchanged basal [35S]GTPgammaS
      binding (controls and PD: 199+/-17 fmol/g and 198+/-21 fmol/g, respectively;
      n.s.) and, at the same time, no change in stimulation (controls and PD: 0.40+/
      4.57% and 1.51+/-2.27%, respectively; n.s.). In cingular gyrus and medial frontal
      gyrus neither the dopamine D2/D3 receptor densities nor the [35S]GTPgammaS
      binding displayed significant differences between PD and age matched control
      brain samples, whereas the [35S]GTPgammaS binding values were markedly higher in
      PD. These preliminary findings may indicate a possible compensatory mechanism in
      striatal regions of PD brains: the loss of the dopamine receptors in the striatum
      appears to be compensated by an increased post-synaptic intracellular signal
      transduction route activity. However, the accurate interpretation of the present
      findings requires detailed further studies.

PMID- 22480733
TI  - Influence of peers and friends on children's and adolescents' eating and activity
      behaviors.
AB  - Obesity during childhood and adolescence is a growing problem in the United
      States, Canada, and around the world that leads to significant physical,
      psychological, and social consequences. Peer experiences have been theoretically
      and empirically related to the "Big Two" contributors to the obesity epidemic,
      unhealthy eating and physical inactivity. In this article, we synthesize the
      empirical literature on the influence of peers and friends on youth's eating and
      physical activity. Limitations and issues in the theoretical and empirical
      literatures are also discussed, along with future research directions. In
      conclusion, we argue that the involvement of children's and adolescents' peer
      networks in prevention and intervention efforts may be critical for promoting and
      maintaining positive behavioral health trajectories. However, further theoretical
      and empirical work is needed to better understand the specific mechanisms
      underlying the effects of peers on youth's eating and physical activity.

PMID- 22480735
TI  - The effects of acute exercise on cognitive performance: a meta-analysis.
AB  - There is a substantial body of literature related to the effects of a single
      session of exercise on cognitive performance. The premise underlying this
      research is that physiological changes in response to exercise have implications
      for cognitive function. This literature has been reviewed both narratively and
      meta-analytically and, although the research findings are mixed, researchers have
      generally concluded that there is a small positive effect. The purpose of this
      meta-analysis was to provide an updated comprehensive analysis of the extant
      literature on acute exercise and cognitive performance and to explore the effects
      of moderators that have implications for mechanisms of the effects. Searches of
      electronic databases and examinations of reference lists from relevant studies
      resulted in 79 studies meeting inclusion criteria. Consistent with past findings,
      analyses indicated that the overall effect was positive and small (g=0.097
      n=1034). Positive and small effects were also found in all three acute exercise
      paradigms: during exercise (g=0.101; 95% confidence interval [CI]; 0.041-0.160),
      immediately following exercise (g=0.108; 95% CI; 0.069-0.147), and after a delay
      (g=0.103; 95% CI; 0.035-0.170). Examination of potential moderators indicated
      that exercise duration, exercise intensity, type of cognitive performance
      assessed, and participant fitness were significant moderators. In conclusion, the
      effects of acute exercise on cognitive performance are generally small; however,
      larger effects are possible for particular cognitive outcomes and when specific
      exercise parameters are used.

PMID- 22480736
TI  - Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and
      iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2
      agonist.
AB  - The prostacyclin analogues, iloprost and treprostinil are extensively used in
      treating pulmonary hypertension. Their binding profile and corresponding
      biochemical cellular responses on human prostanoid receptors expressed in cell
      lines, have now been compared. Iloprost had high binding affinity for EP1 and IP
      receptors (Ki 1.1 and 3.9 nM, respectively), low affinity for FP, EP3 or EP4
      receptors, and very low affinity for EP2, DP1 or TP receptors. By contrast,
      treprostinil had high affinity for the DP1, EP2 and IP receptors (Ki 4.4, 3.6 and
      32 nM, respectively), low affinity for EP1 and EP4 receptors and even lower
      affinity for EP3, FP and TP receptors. In functional assays, iloprost had similar
      high activity in elevating cyclic AMP levels in cells expressing the human IP
      receptor and stimulating calcium influx in cells expressing EP1 receptors (EC50
      0.37 and 0.3 nM, respectively) with the rank order of activity on the other
      receptors comparable to the binding assays. As with binding studies, treprostinil
      elevated cyclic AMP with a similar high potency in cells expressing DP1, IP and
      EP2 receptors (EC50 0.6, 1.9 and 6.2 nM, respectively), but had low activity at
      the other receptors. Activation of IP, DP1 and EP2 receptors, as with
      treprostinil, can all result in vasodilatation of human pulmonary arteries.
      However, activation of EP1 receptors can provoke vasoconstriction, and hence may
      offset the IP-receptor mediated vasodilator effects of iloprost. Treprostinil may
      therefore differ from iloprost in its overall beneficial pulmonary vasorelaxant
      profile and other pharmacological actions, especially in diseases where the IP
      receptor is down-regulated.

PMID- 22480737
TI  - Inhibition of thymidine phosphorylase expression by using an HSP90 inhibitor
      potentiates the cytotoxic effect of cisplatin in non-small-cell lung cancer
      cells.
AB  - Elevated thymidine phosphorylase (TP) levels, a key enzyme in the pyrimidine
      nucleoside salvage pathway, are associated with an aggressive disease phenotype
      and poor prognoses. In this study, we examined the role of TP expression in
      relation to the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)
      induced cytotoxicity in two non-small-cell lung cancer (NSCLC) cell lines, A549
      and H1650. Treatment with 17-AAG (0.1-1 MUM) resulted in a decrease in cellular
      TP protein and mRNA levels, which was accompanied by a downregulation of
      phosphorylated MKK1/2-ERK1/2 and AKT protein levels. The 17-AAG treatment
      disrupted the interaction between HSP90 and TP and triggered TP protein
      degradation through the ubiquitin-26S proteasome pathway. Specific inhibition of
      TP expression by siRNA further enhanced the cell death and growth inhibition that
      had been induced by 17-AAG. An enhancement of ERK1/2 or AKT activation by
      transfecting the cancer cells with constitutively active MKK1/2 or AKT expression
      vectors significantly restored the 17-AAG-reduced TP protein levels as well as
      cell viability. In contrast, a combination of U0126 (MKK1/2 inhibitors) or
      LY294002 (PI3K inhibitor) further decreased the TP expression and cell viability
      induced by 17-AAG. Moreover, 17-AAG enhanced the cisplatin-induced cytotoxic
      effect through downregulation of the cisplatin-induced TP expression and ERK1/2
      and AKT activation. Taken together, our results suggest that the down-modulation
      of TP protein induced by 17-AAG represents a key factor in enhancing the
      cytotoxic effects of cisplatin in NSCLC cells.

PMID- 22480738
TI  - Fear of falling and visual field loss from glaucoma.
AB  - OBJECTIVE: To determine if visual field (VF) loss resulting from glaucoma is
      associated with greater fear of falling. DESIGN: Prospective, observational
      study. PARTICIPANTS: Fear of falling was compared between 83 glaucoma subjects
      with bilateral VF loss and 60 control subjects with good visual acuity and
      without significant VF loss recruited from patients followed up for suspicion of
      glaucoma. METHODS: Participants completed the University of Illinois at Chicago
      Fear of Falling Questionnaire. The extent of fear of falling was assessed using
      Rasch analysis. MAIN OUTCOME MEASURES: Subject ability to perform tasks without
      fear of falling was expressed in logits, with lower scores implying less ability
      and greater fear of falling. RESULTS: Glaucoma subjects had greater VF loss than
      control subjects (median better-eye mean deviation [MD] of -8.0 decibels [dB] vs.
      +0.2 dB; P<0.001), but did not differ with regard to age, race, gender,
      employment status, the presence of other adults in the home, body mass index
      (BMI), grip strength, cognitive ability, mood, or comorbid illness (P >= 0.1 for
      all). In multivariate models, glaucoma subjects reported greater fear of falling
      as compared with controls (beta = -1.20 logits; 95% confidence interval [CI], 
      1.87 to -0.53; P = 0.001), and fear of falling increased with greater VF loss
      severity (beta = -0.52 logits per 5-dB decrement in the better eye VF MD; 95% CI,
      -0.72 to -0.33; P<0.001). Other variables predicting greater fear of falling
      included female gender (beta = -0.55 logits; 95% CI, -1.03 to -0.06; P = 0.03),
      higher BMI (beta = -0.07 logits per 1-unit increase in BMI; 95% CI, -0.13 to 
      0.01; P = 0.02), living with another adult (beta = -1.16 logits; 95% CI, -0.34 to
      -1.99 logits; P = 0.006), and greater comorbid illness (beta = -0.53 logits/1
      additional illness; 95% CI, -0.74 to -0.32; P<0.001). CONCLUSIONS: Bilateral VF
      loss resulting from glaucoma is associated with greater fear of falling, with an
      impact that exceeds numerous other risk factors. Given the physical and
      psychological repercussions associated with fear of falling, significant quality
      of-life improvements may be achievable in patients with VF loss by screening for,
      and developing interventions to minimize, fear of falling.

PMID- 22480739
TI  - Anterior corneal aberrations after Descemet's stripping endothelial keratoplasty
      for Fuchs' endothelial dystrophy.
AB  - PURPOSE: To determine the change in anterior corneal high-order aberrations
      (HOAs) after Descemet's stripping endothelial keratoplasty (DSEK) for Fuchs'
      dystrophy, and to compare the HOAs with those of age-matched controls. DESIGN:
      Prospective cohort and cross-sectional study. PARTICIPANTS AND CONTROLS: Forty
      eight eyes with Fuchs' dystrophy were examined before and after DSEK, and were
      compared with 52 eyes of age-matched controls with normal corneas. METHODS:
      Corneas of patients with Fuchs' dystrophy were examined prospectively before and
      at intervals through 2 years after DSEK. Wavefront errors from the anterior
      corneal surface were derived from corneal topograms and were expressed as Zernike
      polynomials through the sixth order. Best-corrected visual acuity (BCVA) was
      measured by the electronic Early Treatment of Diabetic Retinopathy Study
      protocol, and subepithelial haze was measured from the brightness of confocal
      images. Total HOAs were compared before and after DSEK, and with those of age
      matched controls, by using generalized estimating equation models. Relationships
      between HOAs, BCVA, subepithelial haze, and recipient age were determined. MAIN
      OUTCOME MEASURES: Anterior corneal HOAs, BCVA, and subepithelial haze
      (backscattered light). RESULTS: In Fuchs' dystrophy before DSEK, total HOAs (4 mm
      optical zone) from the anterior corneal surface (0.29+/-0.13 MUm) were higher
      than those of controls (0.17+/-0.08 MUm; P<0.001). At 2 years after DSEK, total
      HOAs (0.26+/-0.13 MUm) did not differ from preoperative aberrations (P = 0.99),
      and remained higher than in controls (P<0.001). At 2 years, total HOAs were
      correlated with BCVA (r = 0.59; P<0.001; n = 27), with subepithelial haze (r =
      0.41; P = 0.01; n = 25), and with recipient age (r = 0.59; P<0.001; n = 27).
      CONCLUSIONS: Anterior corneal HOAs are higher in Fuchs' dystrophy than in
      controls, and remain higher through 2 years after DSEK. The aberrated anterior
      surface might be related to anterior corneal ultrastructural changes and haze
      formation in Fuchs' dystrophy, and should not be ignored as a source of decreased
      visual acuity after DSEK.

PMID- 22480740
TI  - Abnormal fundus autofluorescence results of patients in long-term treatment with
      deferoxamine.
AB  - PURPOSE: To describe and classify patterns of abnormal fundus autofluorescence
      (FAF) of patients with beta-thalassemia receiving long-term treatment with
      deferoxamine (DFO). DESIGN: Prospective, cross-sectional, case-control study.
      PARTICIPANTS: A total of 197 consecutive patients with beta-thalassemia major or
      intermedia with at least 10 years of treatment with DFO were recruited in a
      tertiary referral center in Milan, Italy, and were investigated. Seventy-nine
      thalassemic patients without a history of chelation therapy were included as a
      control group. METHODS: All of the patients were investigated using best
      corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal
      scanning laser ophthalmoscopy (cSLO) and were compared with the control group.
      MAIN OUTCOME MEASURES: Identification of abnormal FAF patterns in thalassemic
      patients treated with long-term DFO and their progression and relationship with
      visual function. RESULTS: Abnormal FAF not related to other diseases was observed
      in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns:
      minimal change, focal, patchy, and speckled. The abnormal increased or decreased
      FAF was bilateral in all the cases, and only in some cases did it correspond to
      funduscopically visible alterations. There were no FAF abnormalities in the
      control group. During the follow-up, progressive FAF changes related to retinal
      pigment epithelium (RPE) damage occurred in the patchy pattern, associated with
      decreasing BCVA. Patients with speckled and focal patterns showed limited or no
      changes in FAF during the follow-up. No changes in FAF were found in patients
      with a minimal change pattern. No treated patient with a normal baseline
      examination demonstrated FAF changes. Patients with patterns other than the
      minimal change showed significant BCVA deterioration (P<0.001). CONCLUSIONS:
      Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging.
      Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring
      the status of the macula in patients at risk of DFO toxicity. It may be useful in
      the decision to discontinue or switch the therapy in cases of particular high
      risk for disease progression. The progressive alteration of the RPE suggests an
      important role of pathologic RPE changes in the evolution of visual loss during
      long-term treatment with DFO.

PMID- 22480741
TI  - Regional variations and trends in the prevalence of diagnosed glaucoma in the
      Medicare population.
AB  - PURPOSE: To determine the prevalence of diagnosed glaucoma in the Medicare
      population and to assess regional variations and trends. DESIGN: Retrospective,
      cross-sectional study. PARTICIPANTS: A 5% random sample of Medicare beneficiaries
      aged >= 65 years, excluding those in health maintenance organizations. METHODS:
      All claims with a glaucoma diagnosis code submitted by ophthalmologists,
      optometrists, or ambulatory surgery centers were used to estimate prevalence of
      the diagnosis of glaucoma for each year from 2002 to 2008. Regional variation in
      diagnosed glaucoma was examined in 9 large geographic regions and in 179 smaller
      subregions, controlling for patient characteristics and provider supply. MAIN
      OUTCOME MEASURES: The prevalence of diagnosed open-angle glaucoma suspect (OAG
      s), open-angle glaucoma (OAG), angle-closure glaucoma suspect (ACG-s), and angle
      closure glaucoma (ACG), trends over time, and regional variations in prevalence.
      RESULTS: The overall prevalence increased from 10.4% in 2002 to 11.9% by 2008,
      largely owing to increase in diagnosed OAG-s (from 3.2% to 4.5%; P<0.001). The
      relative prevalence of diagnosed OAG compared with diagnosed ACG was 32:1. In
      2008, multivariable models showed that the New England and Mid-Atlantic regions
      had 1.7 times more diagnosed OAG-s than the reference region (East South Central;
      New England: odds ratio [OR], 1.66; 95% confidence interval [CI], 1.58-1.75; Mid
      Atlantic: OR, 1.66; 95% CI, 1.59-1.73). The odds of diagnosed OAG was 36% higher
      in New England (OR, 1.36; 95% CI, 1.30-1.42) and 31% higher in the Mid-Atlantic
      (OR, 1.31; 95% CI, 1.26-1.36) than in the reference region. The New England and
      Mid-Atlantic regions had the highest odds of diagnosed ACG-s and the Mid-Atlantic
      region had the highest odds of diagnosed ACG. Among 179 subregions, the New York
      area had high diagnosis rates of all glaucoma types. CONCLUSIONS: The relative
      prevalence of diagnosed ACG compared with diagnosed OAG was lower than expected
      from population-based data, possibly owing to failure to perform gonioscopy.
      Substantial regional differences in diagnosed rates existed for all types of
      glaucoma, even after adjusting for patient characteristics and provider
      concentration, suggesting possible overdiagnosis in some areas and/or
      underdiagnosis in other areas. Regionally higher diagnosis rates in the New York
      area deserve further study.

PMID- 22480742
TI  - Diagnostic ability of a linear discriminant function for spectral-domain optical
      coherence tomography in patients with multiple sclerosis.
AB  - PURPOSE: To calculate and validate a linear discriminant function (LDF) for
      spectral-domain optical coherence tomography (OCT) to improve the diagnostic
      ability of retinal nerve fiber layer (RNFL) thickness parameters for the
      detection of multiple sclerosis (MS). DESIGN: Observational cross-sectional
      study. PARTICIPANTS: Patients with multiple sclerosis (n = 115) and age-matched
      healthy subjects (n = 115) were enrolled in the study. METHODS: The Spectralis
      OCT system (Heidelberg Engineering, Heidelberg, Germany) was used to obtain the
      circumpapillary RNFL thickness in both eyes of each participant. MAIN OUTCOME
      MEASURES: A validating set including 60% of the study subjects (69 healthy
      individuals and 69 patients with MS) was used to test the performance of the LDF
      in an independent population. Receiver operating characteristic (ROC) curves were
      plotted and compared with the RNFL parameters measured using OCT. Sensitivity and
      specificity were used to evaluate diagnostic performance. RESULTS: The optimized
      function was 4.965 - 0.40 * (mean thickness 15-30 degrees) - 0.17 * (mean
      thickness 300-315 degrees) + 2.743 - 0.032 * (mean thickness 105-120 degrees) -
      0.031 * (mean thickness 120-135 degrees) - 0.018 * (mean thickness 225-240
      degrees). The largest area under the ROC curve was 0.834 for our LDF in the
      validating population. At 95% fixed specificity, the LDF yielded the highest
      sensitivity values. CONCLUSIONS: Measurements of RNFL thickness obtained with
      Spectralis OCT had good ability to differentiate between healthy individuals and
      individuals with MS. On the basis of the area under the ROC curve, the LDF
      performed better than any single parameter.

PMID- 22480743
TI  - Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal
      injections.
AB  - PURPOSE: To report the incidence of endophthalmitis in association with different
      antibiotic prophylaxis strategies after intravitreal injections of anti-vascular
      endothelial growth factors and triamcinolone acetonide. DESIGN: Retrospective,
      comparative case series. PARTICIPANTS: Fifteen thousand eight hundred ninety-five
      intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone
      acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January
      5, 2005, and August 31, 2010. The number of injections was determined from
      billing code and patient records. METHODS: The indications for injection included
      age-related macular degeneration, diabetic macular edema, central and branch
      retinal vein occlusion, and miscellaneous causes. Three strategies of topical
      antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics
      given for 5 days after each injection, (2) antibiotics given immediately after
      each injection, and (3) no antibiotics given. MAIN OUTCOME MEASURES: The primary
      outcome measures were the incidence of culture-positive endophthalmitis and
      culture-negative cases of suspected endophthalmitis. RESULTS: Nine eyes of 9
      patients with suspected endophthalmitis after injection were identified. Three of
      the 9 cases had culture-positive results. The overall incidence of
      endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of
      suspected endophthalmitis and culture-proven endophthalmitis after injection was
      6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture
      positive endophthalmitis and culture-negative cases of suspected endophthalmitis,
      the incidence per injection was 5 in 8259 for patients who were given antibiotics
      for 5 days after injection, 2 in 2370 for those who received antibiotics
      immediately after each injection, and 2 in 5266 who received no antibiotics.
      However, if considering culture-proven endophthalmitis alone, the use of topical
      antibiotics, given immediately or for 5 days after injection, showed lower rates
      of endophthalmitis compared with those without postinjection antibiotics. The
      risk of endophthalmitis after intravitreal injection varied among agents that
      were used. Among the 9 cases of clinically suspected endophthalmitis, regardless
      of prophylactic strategies used, the incidence of endophthalmitis per injection
      was 2 in 935 for triamcinolone acetonide, 3 in 9453 for ranibizumab, and 4 in
      5386 for bevacizumab. CONCLUSIONS: The overall rate of intravitreal injection
      related endophthalmitis is greater with the use of topical antibiotics, given
      immediately or for 5 days after the injection, compared with no antibiotics.

PMID- 22480744
TI  - A novel noninvasive detection method for retinal nonperfusion using confocal red
      free imaging.
AB  - PURPOSE: To report confocal red-free blue reflectance imaging as a novel,
      noninvasive imaging modality for the detection of retinal nonperfusion and to
      compare its effectiveness with that of fluorescein angiography (FA) in diabetic
      retinopathy (DR) and retinal vein occlusion (RVO). DESIGN: Evaluation of
      diagnostic technology, retrospective observational case series. PARTICIPANTS: We
      enrolled 54 eyes of 44 patients with DR or RVO that had definite retinal
      nonperfusion on FA. METHODS: All patients underwent red-free blue reflectance
      imaging and FA using a confocal scanning laser ophthalmoscope. For all patients,
      macular and midperipheral retinal nonperfusion were identified on both confocal
      red-free and corresponding FA images, and were delineated by 2 independent
      readers. We evaluated the correspondence of the 2 imaging methods by comparing
      the sizes of the delineated areas and obtaining the overlapping ratio after image
      processing. MAIN OUTCOME MEASURES: Comparison of size and overlapping
      correspondence between delineated area of retinal nonperfusion obtained by FA and
      confocal red-free imaging. RESULTS: Image analysis showed a high correlation
      (r>0.9) in the mean size of retinal nonperfusion between confocal red-free and
      corresponding FA images with DR or RVO. Reliable agreement between the 2 methods
      was confirmed by size comparisons (P = 0.563) and overlapping correspondence
      (overlapping ratio, 0.76) of the delineated area. CONCLUSIONS: Our findings
      suggest that confocal red-free imaging is a simple, reliable, safe, and
      noninvasive method for effectively plotting retinal nonperfusion. This procedure,
      first reported herein, has the potential to be used for the noninvasive detection
      and quantification of retinal nonperfusion in screening, initial evaluation,
      treatment, and follow-up of progressive ischemic retinopathy such as DR and RVO.

PMID- 22480745
TI  - Congenital ectropion uvea and mechanisms of glaucoma in neurofibromatosis type 1:
      new insights.
AB  - OBJECTIVE: To describe the clinicopathologic features of congenital ectropion
      uvea associated with glaucoma in neurofibromatosis-1 (NF-1). DESIGN:
      Retrospective case series. PARTICIPANTS AND CONTROLS: Five cases of NF-1
      associated with glaucoma, from which enucleated eyes were available, and 2 eye
      bank eyes used as controls. METHODS: The clinical features and courses of these
      patients were reviewed. Formalin-fixed, paraffin-embedded eyes were examined by
      light and electron microscopy. Immunohistochemistry using antineurofibromin, anti
      glial fibrillary acidic protein, and antivimentin was performed in 3 patients.
      Gene expression of the mitogen-activated protein kinase (MAPK) signaling pathway
      was examined in corneal endothelial cells in 1 patient. MAIN OUTCOME MEASURES:
      Cause of glaucoma in patients with ectropion uvea and NF-1. RESULTS: The age of
      patients at the time of glaucoma diagnosis ranged from birth to 13 years. Four of
      the 5 patients had megalocornea and buphthalmos at presentation. Ectropion uvea
      was noted clinically in 2 patients, but was demonstrated histopathologically in
      all 5 patients. On histopathologic examination, all patients had varying degrees
      of angle closure secondary to endothelialization of the anterior chamber angle.
      Uveal neurofibromas were noted in all patients; anteriorly displaced ciliary
      processes were noted in 4 of 5 patients who demonstrated ciliary body involvement
      with neurofibromas. Absence of Schlemm's canal was observed. The endothelial
      cells lining the closed angle demonstrated positive stain results with the
      vimentin antibody. Positive antineurofibromin immunolabeling was detected in
      normal control corneal endothelium, but was absent in corneal endothelium in
      patients with endothelialization of the angle. Upregulation of genes from the
      MAPK signaling pathway was demonstrated in the corneal endothelial cells isolated
      from the NF-1 eyes. CONCLUSIONS: Ectropion uvea in NF-1 glaucoma is secondary to
      endothelialization of the anterior chamber angle and is associated commonly with
      severe pediatric glaucoma in NF-1 patients. The endothelial cell proliferation
      may be related to overexpression of the Ras (Rat sarcoma)-MAPK genes in these
      eyes.

PMID- 22480746
TI  - B-cell targeted treatments for lupus: the journey counts as much as the
      destination.
AB  - Obstacles facing therapeutic trials in systemic lupus erythematosus (SLE) include
      the low incidence, seriousness, complexity, and clinical polymorphism of the
      disease. A large-scale multicenter design has been required in most cases. Over
      the last few years, several biologics have been evaluated as treatments for lupus
      nephritis or for the skin and joint manifestations of SLE. The central role for
      the B-cell in SLE, together with improved knowledge of the targets on the B-cell
      surface, has prompted efforts to develop monoclonal antibodies as treatments for
      SLE. The two available monoclonal antibodies are rituximab (anti-CD20 antibody)
      and belimumab (anti-BlyS antibody). The results obtained with belimumab were used
      to develop a new measurement tool, the SLE Responder Index (SRI), and prompted an
      application for a license to use belimumab in SLE. Other targets identified on
      the B-cell surface are being evaluated.

PMID- 22480747
TI  - Efficacy of low-dose etanercept (25 mg/week): how much do we know?

PMID- 22480748
TI  - Effects of polymorphisms in TRAILR1 and TNFR1A on the response to anti-TNF
      therapies in patients with rheumatoid and psoriatic arthritis.
AB  - OBJECTIVES: As the role of polymorphisms in death receptors (DRs) such as Tumor
      Necrosis Factor-related Apoptosis-inducing Ligand Receptor 1 (TRAIL-R1) and Tumor
      Necrosis Factor Receptor 1A (TNF-R1A) on the response to anti-TNF therapy remains
      unknown, we evaluated the association between TRAILR1 and TNFR1A gene
      polymorphisms (rs20575/C626G and rs767455/G36A) and the pharmacogenetics of
      patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated
      with TNFalpha blockers. METHODS: One hundred and forty-five patients (90 RA and
      55 PsA) treated with anti-TNFalpha therapy (RA: 75 infliximab, 8 etanercept, 7
      adalimumab. PsA: 27 infliximab, 19 etanercept, 9 adalimumab) were genotyped for
      TRAILR1 and TNFR1A polymorphisms by allelic discrimination. The response to anti
      TNFalpha was assessed by EULAR criteria. RESULTS: In RA, the TRAILR1 CC genotype
      was associated with a better response after 3 and 6 months of anti-TNFalpha
      treatment (CC: 91.7% vs. CG/GG: 62.2%; P=0.019, and CC: 82.6% vs. CG/GG: 56.1%;
      P=0.019, respectively). Similar results were observed in only infliximab-treated
      RA patients. With respect to the TNFR1A polymorphism, there was an association
      between the AA genotype and a poorer response at 3 months in RA patients (AA:
      39.3% vs. AG/GG: 19.0%; P=0.04). In PsA, TRAILR1 CC genotype was only associated
      with EULAR response to infliximab at 6 months (CC: 71.4% vs CG/GG: 50%P=0.048).
      In contrast to RA, the TNFR1 polymorphism in PsA was associated with a better
      response at 3 months (AA 88% vs AG/GG 58.9%; P=0.04). CONCLUSIONS: This study
      provides the first evidence that a polymorphism in TRAILR1 influences the
      response to anti-TNFalpha therapy in RA and also suggests that TNFR1A
      polymorphism may have opposing effects on the response to anti-TNFalpha in RA and
      PsA.

PMID- 22480749
TI  - The latent structure of attention deficit/hyperactivity disorder in an adult
      sample.
AB  - The vast majority of studies that have examined the latent structure of attention
      deficit/hyperactivity disorder (ADHD) in children and adolescents have concluded
      that ADHD has a dimensional latent structure. In other words, ADHD symptomatology
      exists along a continuum and there is no natural boundary or qualitative
      distinction (i.e., taxon) separating youth with ADHD from those with subclinical
      inattention or hyperactivity/impulsivity problems. Although adult ADHD appears to
      be less prevalent than ADHD in youth (which could suggest a more severe adult
      ADHD taxon), researchers have yet to examine the latent structure of ADHD in
      adults. The present study used a sample (N = 600) of adults who completed a self
      report measure of ADHD symptoms. The taxometric analyses revealed a dimensional
      latent structure for inattention, hyperactivity/impulsivity, and ADHD. These
      findings are consistent with previous taxometric studies that examined ADHD in
      children and adolescents, and with contemporary polygenic and multifactorial
      models of ADHD.

PMID- 22480750
TI  - Effect of primary versus revisional Roux-en-Y gastric bypass: inferior weight
      loss of revisional surgery after gastric banding.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding is a popular and effective
      restrictive bariatric procedure. However, with longer follow-up, it has become
      clear that a considerable number of patients require revisional surgery, of which
      Roux-en-Y gastric bypass (RYGB) is the most commonly performed procedure. Studies
      that compared the outcomes of primary RYGB and revisional RYGB have not been
      conclusive. Our objective was to determine whether significant differences exist
      in the 1-year outcomes between primary RYGB (prim-RYGB) and revisional RYGB after
      laparoscopic adjustable gastric banding (rev-RYGB) at a major training hospital
      in The Netherlands. METHODS: All prim-RYGB and rev-RYGB procedures performed from
      2007 to 2009 were analyzed. Data were collected regarding weight loss,
      hospitalization, operative time, postoperative complications, and co-morbidities.
      RESULTS: A total of 292 RYGB procedures were performed: 66 rev-RYGB and 226 prim
      RYGB procedures. The operative time was significantly shorter in the prim-RYGB
      group (136.6+/-37.5 versus 167.5+/-40.6 min; P<.0001). No significant differences
      were found in hospitalization time (4.4+/-1.7 versus 4.9+/-2.4 d; P= .063) or
      complication rate (14.7% versus 15.2%; P=.962). No deaths occurred in either
      group. The number of patients with resolved diabetes and hypertension did not
      differ between the 2 groups (50.1% versus 23.1%; P=.116; and 40.7% versus 25.0%;
      P=.384, respectively). Weight loss was significantly greater in the prim-RYGB
      group in terms of excess weight loss (71.6%+/-20.8% versus 48.4%+/-26.8%;
      P<.0001), body mass index reduction (13.0+/-3.8 versus 10.2+/-5.6 kg/m(2);
      P<.0001), absolute weight loss (37.4+/-11.5 versus 29.3+/-17.2 kg; P=.001), and
      percentage of weight loss (29.7%+/-8% versus 21.7%+/-11.5%; P<.0001). CONCLUSION:
      rev-RYGB is a safe procedure with outcomes similar to those of prim-RYGB in terms
      of complication rate, hospitalization time, and effect on co-morbidity. Weight
      loss, however, was significantly less after rev-RYGB than after prim-RYGB.

PMID- 22480751
TI  - Effect of bypassing the proximal gut on gut hormones involved with glycemic
      control and weight loss.
AB  - BACKGROUND: The reported remission of type 2 diabetes in patients undergoing Roux
      en-Y gastric bypass has brought the role of the gut in glucose metabolism into
      focus. Our objective was to explore the differential effects on glucose
      homeostasis after oral versus gastrostomy glucose loading in patients with Roux
      en-Y gastric bypass at an academic health science center. METHODS: A comparative
      controlled investigation of oral versus gastrostomy glucose loading in 5 patients
      who had previously undergone gastric bypass and had a gastrostomy tube placed in
      the gastric remnant for feeding. A standard glucose load was administered either
      orally (day 1) or by the gastrostomy tube (day 2). The plasma levels of glucose,
      insulin, glucagon-like peptide 1 and peptide YY were measured before and after
      glucose loading. RESULTS: Exclusion of the proximal small bowel from glucose
      passage induced greater plasma insulin, glucagon-like peptide 1, and peptide YY
      responses compared with glucose loading by way of the gastrostomy tube (P <.05).
      CONCLUSIONS: Exclusion of glucose passage through the proximal small bowel
      results in enhanced insulin and gut hormone responses in patients after gastric
      bypass. The gut plays a central role in glucose metabolism and represents a
      target for future antidiabetes therapies.

PMID- 22480753
TI  - Vocal release time: a quantification of vocal offset.
AB  - OBJECTIVE: To determine the vocal release time (VRT) for linguistically
      unconstrained voice offsets in a healthy young adult population. STUDY DESIGN:
      Sound pressure (SP) and electroglottographic (EGG) recordings were obtained for
      57 female and 55 male subjects while producing multiple tokens of three tasks
      (sustained /alpha:/, "always," and "hallways") at comfortable pitch and loudness.
      METHODS: SP and EGG signals were digitally time reversed and generalized
      sinusoidal models of the SP and EGG signals were obtained to compare rates of
      amplitude change. VRT was computed from the time lag of the cross-correlation
      function. RESULTS: Adjusted mean VRT values were significantly greater for
      females than for males. There was no systematic effect of age on VRT. However, 25
      29-year old and >40 year old females showed shorter VRT values than the youngest
      female age group. CONCLUSIONS: Normative data are presented for a new measure of
      the duration of vocal offset, VRT. Acquisition of this measure requires little
      user intervention, thereby minimizing effects of subjective decision making.
      Comparison with previously reported vocal attack time (VAT) values for the same
      population suggests phenomenological differences between linguistically and
      physiologically constrained voice onsets and unconstrained voice offsets.

PMID- 22480754
TI  - Effects of vocal intensity and vowel type on cepstral analysis of voice.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study was to specifically examine the
      effects of vocal loudness/intensity condition and vowel type on cepstral analysis
      measurements. STUDY DESIGN: Experimental, mixed design. METHODS: Sustained vowel
      samples of /i/, /alpha/, /u/, and /ae/ were elicited from 92 healthy male and
      female subjects between the ages of 18 and 30 years at three different vocal
      loudness conditions: (1) "Comfortable pitch and loudness," (2) "As softly as
      possible without whispering," and (3) "As loudly as possible, without
      screaming/straining the voice or tensing of the neck region." Recordings were
      made using a calibrated headset microphone and digitized to computer. Vowel
      samples were analyzed for vocal intensity (decibels), fundamental frequency (F0
      in Hertzz), and relative amplitude of the smoothed cepstral peak prominence (CPPs
      in decibels). RESULTS: Significant main effects of loudness condition (with a
      significant increase in CPPs from quiet to comfortable to loud voice) and gender
      (males having significantly greater mean CPPs than females) were observed. In
      addition, results indicated that vowel type had a significant effect on the CPP
      (greater CPPs for low vowels [/alpha/ and /ae/] vs high vowels [/i/ and /u/]).
      CONCLUSIONS: The results of this study indicate that both the loudness/intensity
      of vowel elicitation and vowel type should be monitored closely in both research
      and clinical situations. Changes in the mode of phonation, as well supraglottal
      changes that effect vocal tract resonances and vocal intensity, appear to combine
      to result in substantial differences in the CPPs for different vocal
      loudness/intensity conditions and vowel types. These results indicate that
      separate cepstral norms are necessary for vowel type, as well as for gender, when
      using cepstral analysis as a clinical tool.

PMID- 22480752
TI  - High-frequency oscillations (HFOs) in clinical epilepsy.
AB  - Epilepsy is one of the most frequent neurological diseases. In focal medically
      refractory epilepsies, successful surgical treatment largely depends on the
      identification of epileptogenic zone. High-frequency oscillations (HFOs) between
      80 and 500Hz, which can be recorded with EEG, may be novel markers of the
      epileptogenic zone. This review discusses the clinical importance of HFOs as
      markers of epileptogenicity and their application in different types of
      epilepsies. HFOs are clearly linked to the seizure onset zone, and the surgical
      removal of regions generating them correlates with a seizure free post-surgical
      outcome. Moreover, HFOs reflect the seizure-generating capability of the
      underlying tissue, since they are more frequent after the reduction of
      antiepileptic drugs. They can be successfully used in pediatric epilepsies such
      as epileptic spasms and help to understand the generation of this specific type
      of seizures. While mostly recorded on intracranial EEGs, new studies suggest that
      identification of HFOs on scalp EEG or magnetoencephalography (MEG) is possible
      as well. Thus not only patients with refractory epilepsies and invasive
      recordings but all patients might profit from the analysis of HFOs. Despite these
      promising results, the analysis of HFOs is not a routine clinical procedure; most
      results are derived from relatively small cohorts of patients and many aspects
      are not yet fully understood. Thus the review concludes that even if HFOs are
      promising biomarkers of epileptic tissue, there are still uncertainties about
      mechanisms of generation, methods of analysis, and clinical applicability. Large
      multicenter prospective studies are needed prior to widespread clinical
      application.

PMID- 22480755
TI  - Ageing well: a global priority.

PMID- 22480756
TI  - Population ageing and health.

PMID- 22480757
TI  - Escalated BEACOPP in advanced Hodgkin's lymphoma.

PMID- 22480758
TI  - Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with
      advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3
      non-inferiority trial.
AB  - BACKGROUND: The intensity of chemotherapy and need for additional radiotherapy in
      patients with advanced stage Hodgkin's lymphoma has been unclear. We did a
      prospective randomised clinical trial comparing two reduced-intensity
      chemotherapy variants with our previous standard regimen. Chemotherapy was
      followed by PET-guided radiotherapy. METHODS: In this parallel group, open-label,
      multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed
      advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to
      receive either eight cycles of BEACOPP(escalated) (8*B(esc) group), six cycles of
      BEACOPP(escalated) (6*B(esc) group), or eight cycles of BEACOPP(14) (8*B(14)
      group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non
      inferiority of the primary endpoint, freedom from treatment failure, was assessed
      using repeated CIs for the hazard ratio (HR) according to the intention-to-treat
      principle. Patients with a persistent mass after chemotherapy measuring 2.5 cm or
      larger and positive on PET scan received additional radiotherapy with 30 Gy; the
      negative predictive value for tumour recurrence of PET at 12 months was an
      independent endpoint. This trial is registered with Current Controlled Trials,
      number ISRCTN32443041. FINDINGS: Of the 2182 patients enrolled in the study, 2126
      patients were included in the intention-to-treat analysis set, 705 in the
      8*B(esc) group, 711 in the 6*B(esc) group, and 710 in the 8*B(14) group. Freedom
      from treatment failure was sequentially non-inferior for the 6*B(esc) and 8*B(14)
      groups as compared with 8*B(esc). 5-year freedom from treatment failure rates
      were 84.4% (97.5% CI 81.0-87.7) for the 8*B(esc) group, 89.3% (86.5-92.1) for
      6*B(esc) group, and 85.4% (82.1-88.7) for the 8*B(14) group (97.5% CI for
      difference between 6*B(esc) and 8*B(esc) was 0.5-9.3). Overall survival in the
      three groups was 91.9%, 95.3%, and 94.5% respectively, and was significantly
      better with 6*B(esc) than with 8*B(esc) (97.5% CI 0.2-6.5). The 8*B(esc) group
      showed a higher mortality (7.5%) than the 6*B(esc) (4.6%) and 8*B(14) (5.2%)
      groups, mainly due to differences in treatment-related events (2.1%, 0.8%, and
      0.8%, respectively) and secondary malignancies (1.8%, 0.7%, and 1.1%,
      respectively). The negative predictive value for PET at 12 months was 94.1% (95%
      CI 92.1-96.1); and 225 (11%) of 2126 patients received additional radiotherapy.
      INTERPRETATION: Treatment with six cycles of BEACOPP(escalated) followed by PET
      guided radiotherapy was more effective in terms of freedom from treatment failure
      and less toxic than eight cycles of the same chemotherapy regimen. Thus, six
      cycles of BEACOPP(escalated) should be the treatment of choice for advanced stage
      Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional
      radiotherapy in this setting. FUNDING: Deutsche Krebshilfe and the Swiss Federal
      Government.

PMID- 22480759
TI  - Betula pendula leaves: polyphenolic characterization and potential innovative use
      in skin whitening products.
AB  - The research of new tyrosinase inhibitors is currently important for the
      development of skin whitening agents; particularly, birch leaves extracts are
      included in many skin cosmetic products. In this study, the potential ability of
      Betula pendula leaves ethanolic extract (BE) was evaluated on mushroom tyrosinase
      activity. Results showed that BE was capable to inhibit dose-dependently l-DOPA
      oxidation catalyzed by tyrosinase. The inhibition kinetics, analyzed by
      Lineweaver-Burk plots, showed a noncompetitive inhibition of BE towards the
      enzyme, using l-DOPA as substrate. The inhibitory mechanism of BE as studied by
      spectrophotometric analysis, demonstrated its ability to chelate copper ion in
      the active site of tyrosinase. In addition, BE exhibited Fe(2+)-chelating ability
      (IC(50)=614.12+/-2.14 MUg/mL), reducing power and radical-scavenging properties
      (IC(50)=137.22+/-1.98 MUg/mL). These results suggest the usefulness of birch
      leaves extracts in cosmetic and pharmaceutical industries for their skin
      whitening and antioxidant effects. Determination of the polyphenolic compounds in
      BE extracts was afterward achieved by means of high-performance liquid
      chromatography (HPLC) with photodiode array (PDA) and mass spectrometry (MS)
      detection. A total of 25 compounds were positively identified, through the
      complementary analytical information, and are reported in such a matrix for the
      first time. Knowledge on the qualitative composition and contents of these
      natural sources in fact represents mandatory information, for rational
      consumption and correlation of the beneficial effects to the specific amounts.

PMID- 22480761
TI  - Outcomes of carotid endarterectomy under general and regional anesthesia from the
      American College of Surgeons' National Surgical Quality Improvement Program.
AB  - OBJECTIVE: Despite multiple studies over more than 3 decades, there still is no
      consensus about the influence of anesthesia type on postoperative outcomes
      following carotid endarterectomy (CEA). The objective of this study was to
      investigate whether anesthesia type, either general anesthesia (GA) or regional
      anesthesia (RA), independently contributes to the risk of postoperative
      cardiovascular complications or death using the American College of Surgeons'
      National Surgical Quality Improvement Program (ACS NSQIP) database. METHODS:
      Retrospective analysis of elective cases of CEA from 2005 through 2009 was
      performed. A propensity score model using 45 covariates, including demographic
      factors, comorbidities, stroke history, measures of general health, and
      laboratory values, was used to adjust for bias and to determine the independent
      influence of anesthesia type on postoperative stroke, myocardial infarction (MI),
      and death. RESULTS: Of 26,070 cases listed in the ACS NSQIP database, GA and RA
      were used in 22,054 (84.6%) and 4016 (15.4%) cases, respectively. Postoperative
      stroke, MI, and death occurred in 360 (1.63%), 133 (0.6%), and 154 (0.70%)
      patients of the GA group, respectively, and in 58 (1.44%), 11 (0.27%), and 27
      (0.67%) patients of the RA group, respectively. Stratification by propensity
      score quintile and adjustment for covariates demonstrated GA to be a significant
      risk factor for postoperative MI with an adjusted odds ratio (OR) and confidence
      interval (CI) of 2.18 (95% CI, 1.17-4.04), P = .01 in the entire study
      population. The OR for MI was 5.41 (95% CI, 1.32-22.16; P = .019) in the subgroup
      of patients with preoperative neurologic symptoms, and 1.44 (95% CI, 0.71-2.90; P
      = .31) in the subgroup of patients without preoperative neurologic symptoms.
      CONCLUSIONS: This analysis of a large, prospectively collected and validated
      multicenter database indicates that GA for CEA is an independent risk factor for
      postoperative MI, particularly in patients with preoperative neurologic symptoms.

PMID- 22480762
TI  - Prior contralateral amputation predicts worse outcomes for lower extremity
      bypasses performed in the intact limb.
AB  - INTRODUCTION: To date, history of a contralateral amputation as a potential
      predictor of outcomes after lower extremity bypass (LEB) for critical limb
      ischemia (CLI) has not been studied. We sought to determine if a prior
      contralateral lower extremity amputation predicts worse outcomes in patients
      undergoing LEB in the remaining intact limb. METHODS: A retrospective analysis of
      all patients undergoing infrainguinal LEB for CLI between 2003 and 2010 within
      hospitals comprising the Vascular Study Group of New England was performed.
      Patients were stratified according to whether or not they had previously
      undergone a contralateral major or minor amputation before LEB. Primary end
      points included major amputation and graft occlusion at 1 year postoperatively.
      Secondary end points included in-hospital major adverse events, discharge status,
      and mortality at 1 year. RESULTS: Of 2636 LEB procedures, 228 (8.6%) were
      performed in the setting of a prior contralateral amputation. Patients with a
      prior amputation compared to those without were younger (66.5 vs 68.7; P = .034),
      more like to have congestive heart failure (CHF; 25% vs 16%; P = .002),
      hypertension (94% vs 85%; P = .015), renal insufficiency (26% vs 14%; P = .0002),
      and hemodialysis-dependent renal failure (14% vs 6%; P = .0002). They were also
      more likely to be nursing home residents (8.0% vs 3.6%; P = .036), less likely to
      ambulate without assistance (41% vs 80%; P < .0002), and more likely to have had
      a prior ipsilateral bypass (20% vs 12%; P = .0005). These patients experience
      increased in-hospital major adverse events, including myocardial infarction (MI;
      8.9% vs 4.2%; P = .002), CHF (6.1% vs 3.4%; P = .044), deterioration in renal
      function (9.0% vs 4.7%; P = .006), and respiratory complications (4.2% vs 2.3%; P
      = .034). They were less likely to be discharged home (52% vs 72%; P < .0001) and
      less likely to be ambulatory on discharge (25% vs 55%; P < .0001). Although
      patients with a prior contralateral amputation experienced increased rates of
      graft occlusion (38% vs 17%; P < .0001) and major amputation (16% vs 7%; P <
      .0001) at 1 year, there was not a significant difference in mortality (16% vs
      10%; P = .160). On multivariable analysis, prior contralateral amputation was an
      independent predictor of both major amputation (odds ratio, 1.73; confidence
      interval, 1.06-2.83; P = .027) and graft occlusion (odds ratio, 1.93; confidence
      interval, 1.39-2.68; P < .0001) at 1 year. CONCLUSIONS: Patients with prior
      contralateral amputations who present with CLI in the intact limb represent a
      high-risk population, even among patients with advanced peripheral arterial
      disease. When considering LEB in this setting, both physicians and patients
      should expect increased rates of perioperative adverse events, increased rates of
      1-year graft occlusion, and decreased rates of limb salvage, when compared with
      patients who have not undergone a contralateral amputation.

PMID- 22480763
TI  - An unusual case of the right subclavian artery aneurysm resulting from long-term
      repetitive blunt chest trauma.
AB  - This case report describes a right subclavian artery aneurysm secondary to long
      term repetitive blunt trauma. A 62-year-old man with a right subclavian artery
      aneurysm had had a history of bird hunting using a shotgun that impacted
      substantially against his right clavicula and shoulder weekly for >20 years. The
      patient underwent open repair with partial sternotomy and distal balloon control.
      The aneurysmal sac was resected, and the right subclavian artery was
      reconstructed with a primary end-to-end anastomosis. Histopathologic examination
      of the resected aneurysmal wall revealed that all three layers of the arterial
      wall were comparatively intact, with fibrosis and lipid deposition in the intima
      and in various degrees of degeneration in the media, suggesting a true aneurysm.

PMID- 22480765
TI  - Ultrasonic vein mapping prior to infrainguinal autogenous bypass grafting reduces
      postoperative infections and readmissions.
AB  - OBJECTIVE: Although duplex vein mapping (DVM) of the great saphenous vein (GSV)
      is common practice, there is no level I evidence for its application. Our
      prospective randomized trial studied the effect of preoperative DVM in
      infrainguinal bypass surgery. METHODS: Consecutive patients undergoing primary
      bypass grafting were prospectively randomized for DVM of the GSV (group A) or no
      DMV of the GSV (group B) before surgery. Society for Vascular Surgery reporting
      standards were applied. RESULTS: From December 2009 to December 2010, 103
      patients were enrolled: 51 (group A) underwent DVM of the GSV, and 52 (group B)
      did not. Group A and group B not differ statistically in age (72.8 vs 71.1
      years), sex (women, 29.4% vs 34.6%), cardiovascular risk factors, body mass index
      (25.9 vs 26.1 kg/m(2)), bypass anatomy, and runoff. Group A and B had equal
      operative time (151.4 vs 151.1 minutes), incisional length (39.4 vs 39.9 cm), and
      secondary bypass patency at 30 days (96.1% vs 96.2%; P = .49). Conduit issues
      resulted in six intraoperative changes of the operative plan in group B vs none
      in group A (P = .014). Median postoperative length of stay was comparable in both
      groups (P = .18). Surgical site infections (SSIs) were classified (in group A vs
      B) as minor (23.5% vs 23.1%; P = 1.0) and major (1.9% vs 21.2%; P = .004).
      Readmissions due to SSIs were 3.9% in group A vs 19.2% in group B (P = .028). Two
      patients in group B died after complications of SSIs. Multivariate analysis
      identified preoperative DVM as the only significant factor influencing the
      development of major SSI (P = .0038). CONCLUSIONS: Routine DVM should be
      recommended for infrainguinal bypass surgery. The study found that preoperative
      DVM significantly avoids unnecessary surgical exploration, development of major
      SSI, and reduces frequency of readmissions for SSI treatment.

PMID- 22480767
TI  - Long-term results after accessory renal artery coverage during endovascular
      aortic aneurysm repair.
AB  - OBJECTIVE: Current information regarding coverage of accessory renal arteries
      (ARAs) during endovascular aneurysm repair (EVAR) is based on small case series
      with limited follow-up. This study evaluates the outcomes of ARA coverage in a
      large contemporary cohort. METHODS: Consecutive EVAR data from January 2004 to
      August 2010 were collected in a prospective database at a University Hospital.
      Patient and aneurysm-related characteristics, imaging studies, and ARA coverage
      versus preservation were analyzed. Volumetric analysis of three-dimensional
      reconstruction computed tomography scans was used to assess renal infarction
      volume extent. Long-term renal function and overall technical success of aneurysm
      exclusion were compared. RESULTS: A cohort of 426 EVARs was identified. ARAs were
      present in 69 patients with a mean follow-up of 27 months (range, 1 to 60
      months). Forty-five ARAs were covered in 40 patients; 29 patients had intentional
      ARA preservation. Patient and anatomic characteristics were similar between
      groups except that ARA coverage patients had shorter aneurysm necks (P = .03).
      Renal infarctions occurred in 84% of kidneys with covered ARAs. There was no
      significant deterioration in long-term glomerular filtration rate when compared
      with patients in the control group. No difference in the rate of endoleak,
      secondary procedures, or the requirement for antihypertensive medications was
      found. CONCLUSIONS: This study is the largest to date with the longest follow-up
      relating to ARA coverage. Contrary to previous reports, renal infarction after
      ARA coverage is common. Nevertheless, coverage is well tolerated based upon
      preservation of renal function without additional morbidity. These results
      support the long-term safety of ARA coverage for EVAR when necessary.

PMID- 22480768
TI  - Molecular characterization of a recent Newcastle disease virus outbreak in
      Jordan.
AB  - Newcastle disease (ND) is a highly contagious viral disease and is a continuous
      threat to the poultry industry worldwide. In the early months of 2011, several
      devastating ND outbreaks occurred in Jordan affecting broilers, layers and
      breeders. The fusion gene of the isolated Newcastle disease virus (NDV) was
      partially amplified by RT-PCR, then directly sequenced. The NDV isolates were
      found to have the motif112RRQKRF117. This motif and a mean death time (MDT) of 46
      h are indicative of the velogenic nature of these NDV isolates. Phylogenetic
      analysis showed that the new NDV strain belongs to the lineage 5d (Aldous et al.,
      2003) and is closely related to the Chinese strain SG/Liaoning/2009. NDV
      outbreaks in 2010 and 2011 have been noted in neighboring countries. Based on the
      high nucleotide similarity between our isolated NDV isolates and the Chinese NDV
      strain, the origin of these recent NDV isolates might be from China.

PMID- 22480769
TI  - [Modern treatment of cricopharyngeal (Zenker's) diverticula].

PMID- 22480770
TI  - New proposals for the International Classification of Diseases-11 revision of
      pain diagnoses.
AB  - The representation of pain diagnoses in current classification systems like
      International Classification of Diseases (ICD)-10 and Diagnostic and Statistical
      Manual of Mental Disorders (DSM)-IV does not adequately reflect the state of the
      art of pain research, and does not sufficiently support the clinical management
      and research programs for pain conditions. Moreover, there is an urgent need to
      harmonize classification of pain syndromes of special expert groups (eg,
      International Classification of Headache Disorders) and general classification
      systems (eg, ICD-11, DSM-V). Therefore, this paper summarizes new developments,
      and proposals for pain diagnoses in revised classification systems. A qualitative
      review of the literature concerning new proposals for classification of pain
      syndromes that are based on consensus groups was conducted. Selected proposals of
      national and international pain societies that are based on consensual processes
      are presented. These proposals can be condensed to be used in ICD-11
      classification. The benefits of considering multidimensional and transdiagnostic
      processes for the classification process are also outlined. The manuscript
      provides options how to transform current pain-specific classification proposals
      to the revision of ICD-11. PERSPECTIVE: Pain research and expertise must be more
      visible in the ICD-11 revision process. A general category for pain diagnoses as
      well as specific pain diagnoses under existing categories of organ-specific
      sections are needed.

PMID- 22480771
TI  - Effective connectivity among brain regions associated with slow temporal
      summation of C-fiber-evoked pain in fibromyalgia patients and healthy controls.
AB  - Temporal summation of "second pain" (TSSP) or "windup" results from the summation
      of C-fiber-evoked responses of dorsal-horn neurons. This phenomenon is dependent
      on stimulus frequency (>=.33 Hz) and relevant to central sensitization and
      chronic pain. Our previous neuroimaging studies characterized brain regions
      associated with TSSP in normal control (NC) and fibromyalgia (FM) groups. During
      an fMRI scan, subjects received sensitivity-adjusted repetitive heat pulses at
      .33 on the right foot. FM subjects required significantly lower stimulus
      intensities than NC to achieve similar TSSP and no significant group differences
      in the pain-related brain activity were detected. In our current study, we asked
      whether the effective connectivity among a set of TSSP-related brain regions
      identified in our previous work differs amongst FM and NC groups. Structural
      equation modeling was used to characterize the effective connectivity amongst a
      priori selected brain areas, including the thalamus, S1, S2, posterior insula,
      and the anterior midcingulate cortex (aMCC) within the left and right
      hemispheres. This analysis confirmed our a priori models of effective
      connectivity among these regions mainly confirmed those hypothesized, yet some
      unpredicted connections were additionally identified (thalamus to aMCC and aMCC
      to S1). While the models of effective connectivity were not identical in the FM
      and NC groups, they were very similar. Additionally, the TSSP related effective
      connectivity of right and left hemisphere regions was very similar. These results
      provide evidence for significant overlap of the fundamental brain mechanisms that
      process sensory and affective information related to TSSP in NC and FM groups.
      PERSPECTIVE: Models of effective connectivity involving pain-related processes
      were estimated with fMRI data from chronic pain and healthy populations. Models
      were estimated in both hemispheres, and although similar, fibromyalgia was
      associated with unique models of pain-related processes. Group differences
      involved the left hemisphere and S1, S2, and posterior insula.

PMID- 22480772
TI  - Adalimumab improves patient-reported outcomes and reduces indirect costs in
      patients with moderate to severe Crohn's disease: results from the CARE trial.
AB  - BACKGROUND AND AIMS: Crohn's disease negatively affects patients' quality of life
      and ability to work. We investigated the impact of adalimumab on work
      productivity, daily activities, and quality of life in an open-label trial
      (N=945). The population comprised both infliximab-naive and -exposed patients,
      including infliximab primary non-responders. METHODS: Patients received
      adalimumab induction therapy (160 mg/80 mg at Weeks 0/2), followed by adalimumab
      40 mg every other week for up to 20 weeks (patients with flares/non-response
      could receive 40 mg weekly at/after Week 12). The Work Productivity and Activity
      Impairment Questionnaire and Short Inflammatory Bowel Disease Questionnaire were
      assessed. Indirect cost savings were estimated based on the average work
      productivity improvements at Week 20. RESULTS: Mean baseline scores indicated
      severe productivity impairment and poor quality of life. At Week 20, 60% of
      infliximab-naive and 47% of infliximab primary non-responders achieved clinically
      important improvements (>=9 points) on the Short Inflammatory Bowel Disease
      Questionnaire, and 51% and 43%, respectively, achieved the minimum clinically
      important difference (improvement >=7 percentage points) for total work
      productivity impairment (non-responder imputation). At Week 20, 64% of infliximab
      naive and 55% of infliximab primary non-responders achieved clinically important
      improvements in total activity impairment. Estimated 20-week total indirect
      productivity-related cost savings were ?3070 per infliximab-naive patient and
      ?2059 per infliximab-exposed patient. CONCLUSIONS: Adalimumab therapy
      significantly improved work productivity and disease-specific quality of life for
      patients with moderate to severe Crohn's disease. Patients who failed prior
      infliximab therapy and patients naive to infliximab benefited from adalimumab,
      with potentially greater benefits for infliximab-naive patients (NCT00409617).

PMID- 22480773
TI  - Evaluation of heat-labile enterotoxins type IIa and type IIb in the pathogenicity
      of enterotoxigenic Escherichia coli for neonatal pigs.
AB  - Type II heat-labile enterotoxins (LT-II) have been reported in Escherichia coli
      isolates from humans, animals, food and water samples. The goal here was to
      determine the specific roles of the antigenically distinguishable LT-IIa and LT
      IIb subtypes in pathogenesis and virulence of enterotoxigenic E. coli (ETEC)
      which has not been previously reported. The prevalence of genes encoding for LT
      II was determined by colony blot hybridization in a collection of 1648 E. coli
      isolates from calves and pigs with diarrhea or other diseases and from healthy
      animals. Only five isolates hybridized with the LT-II probe and none of these
      isolates contained genes for other enterotoxins or adhesins associated with
      porcine or bovine ETEC. Ligated intestinal loops in calves, pigs, and rabbits
      were used to determine the potential of purified LT-IIa and LT-IIb to cause
      intestinal secretion. LT-IIa and LT-IIb caused significant secretion in the
      intestinal loops in calves but not in the intestinal loops of rabbits or pigs. In
      contrast, neonatal pigs inoculated with isogenic adherent E. coli containing the
      cloned genes for LT-I, LT-IIa or LT-IIb developed severe watery diarrhea with
      weight loss that was significantly greater than pigs inoculated with the
      adherent, non-toxigenic parental or vector only control strains. The results
      demonstrate that the incidence of LT-II appeared to be very low in porcine and
      bovine E. coli. However, a potential role for these enterotoxins in E. coli
      mediated diarrhea in animals was confirmed because purified LT-IIa and LT-IIb
      caused fluid secretion in bovine intestinal loops and adherent isogenic strains
      containing cloned genes encoding for LT-IIa or LT-IIb caused severe diarrhea in
      neonatal pigs.

PMID- 22480774
TI  - Effects of cyclophosphamide myelosuppression in adult dogs with latent canine
      herpesvirus-1 infection.
AB  - Latent canine herpesvirus-1 (CHV-1) infection is common in domestic dogs, but
      triggers for viral reactivation and recrudescent CHV-1 disease are poorly
      understood. Cyclophosphamide is a potent immunosuppressive and myelosuppressive
      agent used for the therapy of a variety of neoplastic and immune-mediated canine
      disorders. Cyclophosphamide (200mg/m(2)) was administered to mature dogs latently
      infected with CHV-1 to determine its potential to induce recurrent CHV-1 disease
      and viral shedding. Non-infected dogs and dogs recovered from experimental
      primary ocular CHV-1 infection with experimentally confirmed latent CHV-1
      infection were divided into groups and administered cyclophosphamide or placebo.
      Dogs were monitored for myelosuppression and viral reactivation for 28days using
      clinical and virological outcome measures. Clinical ophthalmic and in vivo ocular
      confocal microscopic examinations were performed at intervals. Samples were
      collected for CHV-1 polymerase chain reaction (PCR), CHV-1 virus neutralizing
      (VN) antibody, and hemogram assays. Myelosuppression (i.e., decreased total
      leukocyte, segmented neutrophil, and erythrocyte counts) was detected on study
      day 7 in dogs administered cyclophosphamide, but not dogs administered placebo.
      There were no abnormalities suggestive of recurrent CHV-1 ocular disease during
      clinical ophthalmic or in vivo confocal microscopic examination in any dogs
      during the study. Ocular CHV-1 shedding was not detected by PCR and CHV-1 VN
      titers remained stable in all dogs. Following study conclusion, the presence of
      reactivatable latency was reconfirmed in the infected dogs by administering
      systemic prednisolone. Myelosuppression elicited by a single dose of
      cyclophosphamide does not result in detectable recurrent ocular CHV-1 infection
      in adult dogs with experimentally induced latent CHV-1 infection.

PMID- 22480775
TI  - Carbapenem resistance in Enterobacteriaceae: here is the storm!
AB  - The current worldwide emergence of resistance to the powerful antibiotic
      carbapenem in Enterobacteriaceae constitutes an important growing public health
      threat. Sporadic outbreaks or endemic situations with enterobacterial isolates
      not susceptible to carbapenems are now reported not only in hospital settings but
      also in the community. Acquired class A (KPC), class B (IMP, VIM, NDM), or class
      D (OXA-48, OXA-181) carbapenemases, are the most important determinants
      sustaining resistance to carbapenems. The corresponding genes are mostly plasmid
      located and associated with various mobile genetic structures (insertion
      sequences, integrons, transposons), further enhancing their spread. This review
      summarizes the current knowledge on carbapenem resistance in Enterobacteriaceae,
      including activity, distribution, clinical impact, and possible novel antibiotic
      pathways.

PMID- 22480776
TI  - Effectiveness of Cissampelos sympodialis and its isolated alkaloid warifteine in
      airway hyperreactivity and lung remodeling in a mouse model of asthma.
AB  - BACKGROUND: Cissampelos sympodialis Eichl. (Menispermaceae) is a plant found in
      Northeastern and Southeast of Brazil and hot water infusion of C. sympodialis
      root bark is largely used in the indigenous and folk medicine to treat several
      inflammatory disorders, including asthma. Asthma is a chronic inflammatory
      allergic disease characterized by airway hyperreactivity (AHR), eosinophil tissue
      infiltration and lung remodeling. The aim of this study was to evaluate the
      therapeutic effect of C. sympodialis and its isolated alkaloid warifteine on
      allergen triggered airway hyperreactivity (AHR) and lung remodeling in murine
      model of asthma. METHODOLOGY/PRINCIPAL FINDINGS: The oral pre-treatment with C.
      sympodialis or warifteine inhibited allergen-induced AHR to inhaled methacholine
      and IL-13 levels in the bronchoalveolar lavage (BAL). In order to investigate the
      therapeutic potential of C. sympodialis and warifteine, animals were treated 1h
      after the last ovalbumin (OVA) challenge in sensitized animals. Similarly to the
      pre-treatment, post-treatment with warifteine was effective to inhibit
      significantly AHR to inhaled methacholine and to reduce IL-13 levels in the BAL.
      In addition, oral pre- or post-treatments with C. sympodialis or warifteine
      reduced OVA-induced eosinophil tissue infiltration, mucus production and
      subepithelial fibrosis to values similar to nonallergic controls. CONCLUSIONS:
      Our data show the anti-allergic and immunoregulatory properties of C.
      sympodialis, acting mostly through the active compound warifteine, to inhibit the
      airway hyperreactivity and lung remodeling through a mechanism at least partially
      dependent of IL-13 and eosinophil inhibition. Therefore placing warifteine as an
      interesting therapeutic candidate in allergic inflammation and corroborating the
      folk medicine use of C. sympodialis as anti-allergic plant.

PMID- 22480777
TI  - Identification of HLA-A*0201-restricted CD8+ T-cell epitope C64-72 from hepatitis
      B virus core protein.
AB  - The efficacy of a potential therapeutic vaccine against chronic hepatitis B virus
      (HBV) infection depends on the development of strong and multi-specific T cell
      responses. The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward HBV
      core antigen (HBcAg) has been shown to be critical for the outcomes of HBV
      chronic infection. In this study we have identified a previously undescribed HLA
      A*0201-restricted HBcAg-specific CTL epitope (HBcAg64-72, C64-72, ELMTLATWV). T2
      binding assay showed that C64-72 had high affinity to HLA-A*0201 molecule.
      Functionally, the peptide C64-72 could induce peptide-specific CTLs both in vivo
      (HLA-A2.1/K(b) transgenic mice) and in vitro (PBLs of healthy HLA-A2.1+ donors),
      as demonstrated by interferon-gamma (IFN-gamma) secretion upon stimulation with
      C64-72-pulsed T2 cells or autologous human dendritic cells (DCs) respectively.
      HLA-A*0201-C64-72 tetramer staining revealed the presence of a significant
      population of C64-72-specific CTLs in C64-72-stimulated CD8+ T cells.
      Furthermore, the peptide-specific cytotoxic reactivity and the production of
      perforin and granzyme B of CTLs also increased after stimulation with C64-72
      pulsed autologous DCs. These results indicate that the newly identified epitope
      C64-72 has potential to be used in the development of immunotherapeutic
      approaches to HBV infection.

PMID- 22480778
TI  - Analysis of selective, high protein-protein binding interaction of cohesin
      dockerin complex using biosensing methods.
AB  - Optical biosensors that use fluorescence are promising tools for the analysis of
      target materials such as protein, DNA and other biomaterial. To analyze the
      binding properties of a protein-protein interaction, we constructed fluorescent
      biomarkers based on the cohesin-dockerin interaction, which coordinates the
      assembly of cellulolytic enzymes and scaffolding proteins to produce a cell
      surface multiprotein complex known as the "cellulosome" in some anaerobic
      bacteria. Our 2D-PAGE results displayed diverse binding profiles to the dockerin
      containing cellulosomal proteins produced by Clostridium cellulovorans grown on
      different carbon sources, such as Avicel, xylan and AXP (Avicel:xylan:pectin
      (3:1:1)). Fluorescence intensity analysis indicated that EngE and EngH bound more
      efficiently to Coh6 than to Coh2 or Coh9 (2-fold to 6-fold and 1.5-fold to 5
      fold, respectively), while others cellulosomal proteins displayed similar
      results. In addition, both an enzyme-linked interaction assay (ELIA) and surface
      plasmon resonance (SPR) analyses demonstrated that both EngE and EngH
      preferentially bound cohesin6 versus the other two cohesin molecules. This work
      demonstrated the analysis of the binding patterns between interacting proteins
      using fluorescent biomarkers. We also illustrated the potential of this sensitive
      approach to quantify specific target analytical materials via the example of the
      cohesin-dockerin interaction.

PMID- 22480779
TI  - Sensitive detection of unlabeled oligonucleotides using a paired surface plasma
      waves biosensor.
AB  - Detection of unlabeled oligonucleotides using surface plasmon resonance (SPR) is
      difficult because of the oligonucleotides' relatively lower molecular weight
      compared with proteins. In this paper, we describe a method for detecting
      unlabeled oligonucleotides at low concentration using a paired surface plasma
      waves biosensor (PSPWB). The biosensor uses a sensor chip with an immobilized
      probe to detect a target oligonucleotide via sequence-specific hybridization.
      PSPWB measures the demodulated amplitude of the heterodyne signal in real time.
      In the meantime, the ratio of the amplitudes between the detected output signal
      and reference can reduce the excess noise from the laser intensity fluctuation.
      Also, the common-path propagation of p and s waves cancels the common phase noise
      induced by temperature variation. Thus, a high signal-to-noise ratio (SNR) of the
      heterodyne signal is detected. The sequence specificity of oligonucleotide
      hybridization ensures that the platform is precisely discriminating between
      target and non-target oligonucleotides. Under optimized experimental conditions,
      the detected heterodyne signal increases linearly with the logarithm of the
      concentration of target oligonucleotide over the range 0.5-500 pM. The detection
      limit is 0.5 pM in this experiment. In addition, the non-target oligonucleotide
      at concentrations of 10 pM and 10nM generated signals only slightly higher than
      background, indicating the high selectivity and specificity of this method.
      Different length of perfectly matched oligonucleotide targets at 10-mer, 15-mer
      and 20-mer were identified at the concentration of 150 pM.

PMID- 22480780
TI  - Free will and consciousness: experimental studies.
AB  - What are the folk-conceptual connections between free will and consciousness? In
      this paper I present results which indicate that consciousness plays central
      roles in folk conceptions of free will. When conscious states cause behavior,
      people tend to judge that the agent acted freely. And when unconscious states
      cause behavior, people tend to judge that the agent did not act freely. Further,
      these studies contribute to recent experimental work on folk philosophical
      affiliation, which analyzes folk responses to determine whether folk views are
      consistent with the view that free will and determinism are incompatible
      (incompatibilism) or with the opposite view (compatibilism). Conscious causation
      of behavior tends to elicit pro-free will judgments, even when the causation
      takes place deterministically. Thus, when controlling for consciousness, many
      folk seem to be compatibilists. However, participants who disagree with the
      deterministic or cognitive scientific descriptions given of human behavior tend
      to give incompatibilist responses.

PMID- 22480781
TI  - The Oxford medial unicompartmental knee replacement: survival and the affect of
      age and gender.
AB  - STUDY AIMS: To determine the survival and functional outcome for the phase 3
      Oxford unicompartmental knee replacement (UKR) performed at a single independent
      centre and to assess whether age and gender affect survival. PATIENTS AND
      METHODS: Between 2000 and 2008, 459 consecutive Oxford UKRs were implanted in 392
      patients using a minimally invasive technique. RESULTS: Mean age of patients was
      63.0 years and 53% were female. Mean follow-up was 4.4 years (range 0.5-11.2
      years). No patient was lost to follow-up and 411 (90%) knees had a minimum follow
      up of 2 years. Twenty knees (4.4%) have undergone revision to total knee
      replacement at a mean time of 3.2 years. Aseptic component loosening (n=11)
      accounted for most failures. Cumulative survival was 94.4% at 5 years (95%
      confidence interval 90.9-97.0) and 93.0% at 8 years (95% confidence interval 84.8
      96.2). The median postoperative Oxford knee score was 31.2% (interquartile range
      12.2%-52.1%) at latest follow-up. Age and gender had no statistically significant
      affect on UKR survival. CONCLUSIONS: This large independent series demonstrates
      good medium-term survival and functional outcome can be achieved with the phase 3
      Oxford UKR in appropriately selected patients. Age and gender should not be
      considered contraindications for performing Oxford UKR.

PMID- 22480783
TI  - Early lymphoid development and microenvironmental cues in B-cell acute
      lymphoblastic leukemia.
AB  - B-cell acute lymphoblastic leukemia (B-ALL) is a hematological disorder
      characterized by malignant and uncontrolled proliferation of B-lymphoid precursor
      cells in bone marrow. Over the last few years remarkable advances have been made
      in identifying genetic aberrations, patterns of abnormal transcriptional activity
      controlling early fate decisions and environmental cues that may influence
      leukemic development. In this review we focus on the structure of the early
      lymphoid system and the current knowledge about cell composition and function of
      the hematopoietic microenvironment that might control progenitor cell activity
      and lead to differentiation, proliferation and survival of developing B leukemic
      precursors. Learning the biology of special leukemic niches is central to
      understanding the pathogenesis of B-ALL and for the development of novel
      therapies.

PMID- 22480784
TI  - Extra-corporeal life support, transradial thrombus aspiration and stenting,
      percutaneous blade and balloon atrioseptostomy, all as a bridge to heart
      transplantation to save one life.
AB  - In patients with cardiogenic shock, the Extra-Corporeal Life Support (ECLS) has
      been shown to be lives saving. But, in some situations, it proves inadequate for
      the discharge of the left heart. Several device-based techniques have been
      proposed to decompress the left side either surgically or percutaneously, each of
      them with the proper potential risks and complications. One technique, the
      percutaneous blade and balloon atrioseptostomy that requires transseptal catheter
      based experience and consists of creating an atrial septal defect (ASD) could be
      an elegant technique as an "add on" to the classic assistance making together a
      bridge to partial recovery or to heart transplantation. Herein, we present a case
      of an adult patient who presented with inaugural resistant cardiac arrest with a
      thrombotic occlusion of the left anterior descending artery (LAD) who required
      Extra-Corporeal Life Support, thrombus aspiration, stenting of the culprit
      lesion, and percutaneous blade and balloon atrioseptostomy to bridge "safely" to
      the heart transplantation.

PMID- 22480785
TI  - Solubility of carbohydrates in heavy water.
AB  - The solubility of several mono-(glucose and xylose), di-(sucrose and maltose),
      tri-(raffinose) and cyclic (alpha-cyclodextrin) saccharides in H(2)O and in D(2)O
      were measured over a range of temperatures. The solution enthalpies for the
      different carbohydrates in the two solvents were determined using the vant' Hoff
      equation and the values in D(2)O are presented here for the first time. Our
      findings indicate that the replacement of H(2)O by D(2)O remarkably decreases the
      solubilities of the less soluble carbohydrates, such as maltose, raffinose and
      alpha-cyclodextrin. On the other hand, the more soluble saccharides, glucose,
      xylose, and sucrose, are practically insensitive to the H/D replacement in water.

PMID- 22480787
TI  - Tetrodotoxin does not protect red-spotted newts, Notophthalmus viridescens, from
      intestinal parasites.
AB  - Tetrodotoxin (TTX) and its analogue 6-epiTTX had been detected in the red-spotted
      newt, Notophthalmus viridescens. Thirty specimens of a population from
      Pennsylvania, USA were histologically examined for the presence of intestinal
      parasites. More than 50% were found to be infected with nematodes
      (Trichocephalidae), trematodes or cestodes (Pseudophyllidae). The mean values of
      TTX and 6-epiTTX in parasitized and in non-parasitized newts were not
      significantly different. Using a monoclonal antibody-based immunoenzymatic
      technique, TTX was localized in the intestinal tissue as well as in the parasites
      indicating that they accumulate the toxin and suggesting that TTX and 6-epiTTX
      are not providing protection from parasites to the newts.

PMID- 22480788
TI  - Bipolar radiofrequency plasma ablation induces proliferation and alters cytokine
      expression in human articular cartilage chondrocytes.
AB  - PURPOSE: The aim of the study was to determine the in vitro effects of plasma
      mediated bipolar radiofrequency ablation on human chondrocyte compensatory
      proliferation and inflammatory mediator expression. METHODS: Human articular
      cartilage biopsy specimens, from total knee replacement, and human chondrocytes
      in alginate culture, from patients undergoing autologous chondrocyte
      implantation, were exposed to plasma ablation with a Paragon T2 probe
      (ArthroCare, Austin, TX). Instantaneous chondrocyte death was investigated with
      live/dead assays of biopsy specimens and cell cultures. Chondrocyte proliferation
      was determined by Hoechst staining of DNA on days 3 and 6. Messenger RNA
      expression of IL-1beta, IL-6, IL-8, tumor necrosis factor alpha, high-mobility
      group protein B1, matrix metalloproteinase 13, type IIA collagen, and versican
      was determined on days 3 and 6. RESULTS: Live/dead imaging showed a well-defined
      local margin of cell death ranging from 150 to 200 MUm deep, both in the alginate
      gel and in the biopsy specimens exposed to plasma ablation. The ablation-exposed
      group showed a significant proliferation increase compared with control on day 3
      (P < .043). There were significant increases compared with control in IL-6
      expression on day 3 (P < .020) and day 6 (P < .045) and in IL-8 expression on day
      3 (P < .048). No differences were seen for IL-1beta, tumor necrosis factor alpha,
      high-mobility group protein B1, matrix metalloproteinase 13, type II collagen, or
      versican. CONCLUSIONS: This study has shown that exposure to plasma-mediated
      ablation induces a well-defined area of immediate cell death and a short-term
      increase in proliferation with human articular chondrocytes in vitro. The
      exposure also alters cytokine expression for the same period, causing
      upregulation of IL-6 and IL-8. CLINICAL RELEVANCE: The results show the potential
      of plasma-mediated ablation to cause the onset of a tissue regeneration response
      with human articular cartilage.

PMID- 22480789
TI  - Measurement of aminoterminal propeptide of type I procollagen (PINP) in serum.
AB  - The aminoterminal propeptide of type I procollagen (PINP) in serum is a sensitive
      indicator of the synthesis of type I collagen. Four assays are available for
      PINP, two of them (intact PINP assays) measure the intact propeptide and the
      other two (total PINP assays) also detect a smaller antigen in serum. In many
      clinical situations, these assays give similar information, but renal
      insufficiency increases the concentration of the smaller antigen, influencing
      both the apparent concentration of PINP and assay calibration. Serum PINP is
      mostly affected by changes in bone metabolism. In infants and children, the
      concentration is much higher than in adults. Serum PINP (s-PINP) is a useful
      indicator of disease activity in Paget's disease of bone, in bone metastases of
      osteoblastic nature, and in the follow-up of treatment of osteoporosis. The IFCC
      and IOF recently recommended the use of s-PINP as a reference marker for bone
      formation in studies concerning fracture risk assessment and treatment response.

PMID- 22480791
TI  - An age-adjusted seroprevalence study of Toxoplasma antibody in a Malaysian
      ophthalmology unit.
AB  - Toxoplasma gondii is a public health risk in developing countries, especially
      those located in the tropics. Widespread infection may inflict a substantial
      burden on state resources, as patients can develop severe neurological defects
      and ocular diseases that result in lifelong loss of economic independence. We
      tested sera for IgG antibody from 493 eye patients in Malaysia. Overall age
      adjusted seroprevalence was estimated to be 25% (95% CI: [21%, 29%]). We found
      approximately equal age-adjusted seroprevalence in Chinese (31%; 95% CI: [25%,
      38%]) and Malays (29%; 95% CI: [21%, 36%]), followed by Indians (19%; 95% CI:
      [13%, 25%]). A logistic regression of the odds for T. gondii seroprevalence
      against age, gender, ethnicity and the occurrence of six types of ocular diseases
      showed that only age and ethnicity were significant predictors. The odds for T.
      gondii seroprevalence were 2.7 (95% CI for OR: [1.9, 4.0]) times higher for a
      patient twice as old as the other, with ethnicity held constant. In Malays, we
      estimated the odds for T. gondii seroprevalence to be 2.9 (95% CI for OR: [1.8,
      4.5]) times higher compared to non-Malays, with age held constant. Previous
      studies of T. gondii seroprevalence in Malaysia did not explicitly adjust for
      age, rendering comparisons difficult. Our study highlights the need to adopt a
      more rigorous epidemiological approach in monitoring T. gondii seroprevalence in
      Malaysia.

PMID- 22480792
TI  - Aggregation in quads but not pairs of rats exposed to cat odor or bright light.
AB  - In many prey species aggregation of individuals is a defensive strategy commonly
      employed in response to predators and predator-related cues. However, very little
      work has explored this adaptive response in laboratory rats. It is known that
      individual rats show characteristic defensive responses to predator odors, such
      as hiding, avoidance, inhibition of foraging, feeding and reproduction, and risk
      assessment directed toward the odor source. However, whether these species
      typical responses in individuals are altered in the presence of other
      conspecifics is yet to be characterized. The present study therefore examined the
      defensive response of groups of two rats (dyads) or four rats (quads) to two
      unconditioned stressors: bright ambient light and cat odor (a 2g ball of cat
      fur). The dyads and quads were formed from familiar cage mates and test sessions
      (20 min) occurred in a large open arena (1200 mm(2)) to which the rats had been
      extensively habituated under dark conditions. The results showed that when quads
      of rats were exposed to either cat odor or bright light in this arena, they
      showed characteristic increases in close social proximity, termed "huddling". A
      tight grouping of 3 (triplet) or 4 (quad) rats was commonly seen in response to
      cat fur, while triplets were more commonly seen in response to bright light.
      Interestingly there was no evidence for increased social proximity in dyads
      exposed to either stressor, only in quads. However, cat odor caused other signs
      of fear (such as decreased locomotor activity and increased defecation) in both
      quads and dyads. It is concluded that huddling is a rodent defensive strategy in
      rats when anxiogenic stimuli are encountered by larger groups of rats.

PMID- 22480793
TI  - Spatial distribution of gut juice extractable Cu, Pb and Zn in sediments from the
      Pearl River Estuary, Southern China.
AB  - In this study, we compared the spatial distribution of total metals (Cu, Pb, and
      Zn) and bioaccessible metals, which were quantified by incubating sediments with
      the digestive fluid of sipunculans Sipunculus nudus, in natural sediments of the
      Pearl River Estuary (PRE). The spatial distribution of bioaccessible metal was
      not the same as that of total metals in PRE sediments, which were mainly
      controlled by fine-grained size, total organic carbon (TOC) and Fe. Geochemical
      factors were important in interpreting this different spatial variation. The
      similar spatial variations of bioaccessible Cu and total Cu were related to TOC
      in PRE sediments. Differently from the total Zn, a higher bioaccessible Zn was
      detected near the West Channel of PRE because of a lower TOC. However, the
      distribution of bioaccessible Pb was not significantly related to any sediment
      geochemistry. This study provides a more accurate view of metal pollution in the
      PRE natural sediments.

PMID- 22480794
TI  - Tinzaparin versus dalteparin for periprocedure prophylaxis of thromboembolic
      events in hemodialysis patients: a randomized trial.
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) is cleared predominantly by the
      kidneys and hence there is uncertainty about the safety of its use in
      hemodialysis (HD) patients. Our primary objective was to compare whether
      tinzaparin and dalteparin differentially accumulate in HD patients. STUDY DESIGN:
      Open-label randomized controlled trial. SETTING & PARTICIPANTS: HD patients
      undergoing periprocedure bridging anticoagulation. INTERVENTION: After warfarin
      therapy was discontinued, participants were randomly assigned to either 3 daily
      doses of tinzaparin (175 IU/kg) or dalteparin (200 IU/kg), with 2 intervening HD
      treatments between the first dose of study drug and their procedure. OUTCOMES:
      The primary outcome was predialysis anti-Xa levels 20 to 24 hours after the third
      LMWH dose (therapeutic target, <0.2 IU/mL). Secondary outcomes included
      thromboembolic events and major bleeding. RESULTS: Of 29 eligible and consenting
      patients, 17 patients received tinzaparin and 12 patients received dalteparin.
      Mean predialysis anti-Xa level 20-24 hours after the third LMWH dose was 0.37 +/-
      0.23 (SD) IU/mL for tinzaparin and 0.62 +/- 0.41 IU/mL for dalteparin (P = 0.1),
      indicating clinically important accumulation for both drugs. No invasive
      procedures were canceled due to study drug accumulation. 4 patients experienced
      serious adverse events (1 major bleed after traumatic arteriovenous fistula
      puncture in the tinzaparin arm, 2 non-ST-elevation myocardial infarctions [1 in
      each group], and 1 upper-extremity deep venous thrombosis [dalteparin group]).
      LIMITATIONS: Small sample size. CONCLUSIONS: Dalteparin and tinzaparin
      significantly accumulate in HD patients at therapeutic doses. "Bridging therapy"
      with LMWHs at therapeutic doses in HD patients who require temporary interruption
      of warfarin therapy has the potential for complications and is of uncertain
      benefit. Other anticoagulation strategies, including no bridging therapy or
      intravenous heparin, need comparative evaluation in this unique patient
      population.

PMID- 22480795
TI  - Hepatorenal syndrome: a severe, but treatable, cause of kidney failure in
      cirrhosis.
AB  - Hepatorenal syndrome (HRS) is a unique type of kidney failure that occurs in
      advanced cirrhosis. It is characterized by functional impairment of the kidneys
      due to vasoconstriction of the renal arteries in the setting of preserved tubular
      function and absence of significant histologic abnormalities. Renal
      vasoconstriction in HRS is due to severe vasodilation of the splanchnic arteries
      associated with portal hypertension, leading to a decrease in effective arterial
      blood volume and arterial pressure. HRS commonly develops after a trigger,
      usually a bacterial infection, that disrupts the arterial circulation, but it
      also may occur spontaneously. There are 2 forms of HRS: type 1 is characterized
      by an acute progressive decrease in kidney function and very short survival
      without treatment, whereas type 2 features stable less severe kidney failure and
      longer survival compared with type 1. A liver transplant is the preferred
      treatment for HRS. Pharmacologic treatment with vasoconstrictors to reverse
      splanchnic vasodilation, together with albumin, is effective in 40%-50% of
      patients with type 1 HRS and improves survival. The drug of choice is the
      vasopressin analogue terlipressin. Renal replacement therapy should not be used
      as first-line therapy.

PMID- 22480796
TI  - Optimizing care for patients with CKD.
AB  - Care of patients with chronic kidney disease (CKD) is complex and requires a
      standardized and multidisciplinary approach. A number of strategies have been
      suggested to improve care for patients with CKD, including the development of
      clinical practice guidelines and introduction of chronic disease management (CDM)
      programs. CDM programs represent a proactive approach to care by supporting the
      physician and patient, with an emphasis on prevention of exacerbations and
      complications achieved through a coordinated multidisciplinary team. In addition
      to targeting patients at highest risk, CDM programs also emphasize intensive
      monitoring and proactive follow-up. The expansion of professional roles may be an
      important component in ensuring the success of this approach. Although
      observational studies suggest that specific components of CDM programs may
      improve care for patients with CKD, further research is needed to evaluate the
      program component effectiveness in CKD prevention and management. This includes
      well-conducted randomized trials and long-term follow-up of patients with CKD to
      assess changes in adverse health outcomes.

PMID- 22480797
TI  - The effectiveness of interventions to treat severe acute malnutrition in young
      children: a systematic review.
AB  - BACKGROUND: Severe acute malnutrition (SAM) arises as a consequence of a sudden
      period of food shortage and is associated with loss of a person's body fat and
      wasting of their skeletal muscle. Many of those affected are already
      undernourished and are often susceptible to disease. Infants and young children
      are the most vulnerable as they require extra nutrition for growth and
      development, have comparatively limited energy reserves and depend on others.
      Undernutrition can have drastic and wide-ranging consequences for the child's
      development and survival in the short and long term. Despite efforts made to
      treat SAM through different interventions and programmes, it continues to cause
      unacceptably high levels of mortality and morbidity. Uncertainty remains as to
      the most effective methods to treat severe acute malnutrition in young children.
      OBJECTIVES: To evaluate the effectiveness of interventions to treat infants and
      children aged < 5 years who have SAM. DATA SOURCES: Eight databases (MEDLINE,
      EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CAB Abstracts Ovid,
      Bioline, Centre for Reviews and Dissemination, EconLit EBSCO and The Cochrane
      Library) were searched to 2010. Bibliographies of included articles and grey
      literature sources were also searched. The project expert advisory group was
      asked to identify additional published and unpublished references. REVIEW
      METHODS: Prior to the systematic review, a Delphi process involving international
      experts prioritised the research questions. Searches were conducted and two
      reviewers independently screened titles and abstracts for eligibility. Inclusion
      criteria were applied to the full texts of retrieved papers by one reviewer and
      checked independently by a second. Included studies were mapped to the research
      questions. 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. Studies were synthesised through a narrative review
      with tabulation of the results. RESULTS: A total of 8954 records were screened,
      224 full-text articles were retrieved, and 74 articles (describing 68 studies)
      met the inclusion criteria and were mapped. No evidence focused on treatment of
      children with SAM who were human immunodeficiency virus sero-positive, and no
      good-quality or adequately reported studies assessed treatments for SAM among
      infants < 6 months old. One randomised controlled trial investigated fluid
      resuscitation solutions for shock, with none adequately treating shock. Children
      with acute diarrhoea benefited from the use of hypo-osmolar oral rehydration
      solution (H-ORS) compared with the standard World Health Organization-oral
      rehydration solution (WHO-ORS). WHO-ORS was not significantly different from
      rehydration solution for malnutrition (ReSoMal), but the safety of ReSoMal was
      uncertain. A rice-based ORS was more beneficial than glucose-based ORSs, and
      provision of zinc plus a WHO-ORS had a favourable impact on diarrhoea and need
      for ORS. Comparisons of different diets in children with persistent diarrhoea
      produced conflicting findings. For treating infection, comparison of amoxicillin
      with ceftriaxone during inpatient therapy, and routine provision of antibiotics
      for 7 days versus no antibiotics during outpatient therapy of uncomplicated SAM,
      found that neither had a significant effect on recovery at the end of follow-up.
      No evidence mapped to the next three questions on factors that affect
      sustainability of programmes, long-term survival and readmission rates, the
      clinical effectiveness of management strategies for treating children with
      comorbidities such as tuberculosis and Helicobacter pylori infection and the
      factors that limit the full implementation of treatment programmes. Comparison of
      treatment for SAM in different settings showed that children receiving inpatient
      care appear to do as well as those in ambulatory or home settings on
      anthropometric measures and response time to treatment. Longer-term follow-up
      showed limited differences between the different settings. The majority of
      evidence on methods for correcting micronutrient deficiencies considered zinc
      supplements; however, trials were heterogeneous and a firm conclusion about zinc
      was not reached. There was limited evidence on either supplementary potassium or
      nicotinic acid (each produced some benefits), and nucleotides (not associated
      with benefits). Evidence was identified for four of the five remaining questions,
      but not assessed because of resource limitation. LIMITATIONS: The systematic
      review focused on key questions prioritised through a Delphi study and, as a
      consequence, did not encompass all elements in the management of SAM. In focusing
      on evidence from controlled studies with the most rigorous designs that were
      published in the English language, the systematic review may have excluded other
      forms of evidence. The systematic review identified several limitations in the
      evidence base for assessing the effectiveness of interventions for treating young
      children with severe acute malnutrition, including a lack of studies assessing
      the different interventions; limited details of study methods used; short follow
      up post intervention or discharge; and heterogeneity in participants,
      interventions, settings, and outcome measures affecting generalisability.
      CONCLUSIONS: For many of the most highly ranked questions evidence was lacking or
      inconclusive. More research is needed on a range of topic areas concerning the
      treatment of infants and children with SAM. Further research is required on most
      aspects of the management of SAM in children < 5 years, including intravenous
      resuscitation regimens for shock, management of subgroups (e.g. infants < 6
      months old, infants and children with SAM who are human immunodeficiency virus
      sero-positive) and on the use of antibiotics.

PMID- 22480798
TI  - Cachexia assessed by bioimpedance vector analysis as a prognostic indicator in
      chronic stable heart failure patients.
AB  - BACKGROUND: This study explored whether the cachectic state assessed by
      bioimpedance vector analysis provides additional prognostic information about
      mortality from all causes. METHODS: We included 519 consecutive patients with
      stable chronic heart failure (mean age 62.5 +/- 16.4 y; 286 males). Cachexia was
      identified in those subjects who fell outside the right lower quadrant of the
      reference curve of 95% on the resistance/reactance graph [bioelectrical impedance
      vectorial analysis (BIVA)-cachexia]. Clinical, anthropometric, and biochemical
      data were also evaluated. RESULTS: Patients with BIVA-cachexia (n = 196, 37.8%)
      were older and had significantly lower ejection fraction, handgrip strength,
      serum albumin, total cholesterol, and triglycerides. The frequency of patients
      with body mass index < 20, decreased muscle strength, hypoalbuminemia, anemia,
      anorexia, New York Heart Association functional classes III/IV and edema, as well
      as creatinine levels, resistance/height, and impedance index was significantly
      higher in the cachexia group. During 29 +/- 11 mo of follow-up, 39 (19.9%)
      patients with BIVA-cachexia and 38 (11.7%) patients without BIVA-cachexia (P <
      0.0001) died. CONCLUSIONS: The cachectic state is an independent risk factor for
      mortality in chronic heart failure patients. BIVA could represent a valuable tool
      to assess presence of cachexia as changes in body cell mass in heart failure
      patients because provide information additional to weight loss.

PMID- 22480799
TI  - A moderate-sodium DASH-type diet improves mood in postmenopausal women.
AB  - OBJECTIVE: We compared the effect on mood of a moderate sodium Dietary Approaches
      to Stop Hypertension-type diet, which included lean red meat (vitality diet
      [VD]), with a healthy diet (HD; decreased fat and increased wholegrain breads and
      cereal). METHODS: In a randomized, parallel intervention study, postmenopausal
      women were assigned to the VD or HD for 14 wk. Mood was measured every 2 wk by
      the Profile of Mood States. Dietary adherence was assessed using 24-h urine
      collections. Data were analyzed using one-way between-groups multivariate
      analysis of variance and correlations. RESULTS: Forty-six subjects completed the
      VD and 49 completed the HD. The two groups showed an improvement in anger,
      confusion, depression, fatigue, tension, vigor, and the Profile of Mood States
      global score over the length of the intervention (P < 0.01 for time), but there
      was a significant diet group by time effect for anger (P < 0.05), such that anger
      improved more in the VD compared with the HD group. For the two groups combined,
      urinary sodium excretion was associated with the Profile of Mood States global
      score, such that a low sodium intake was associated with a better mood (r =
      0.267, P < 0.05). In addition, red meat consumption (a component of the VD) was
      associated with a decrease in depression (r = -0.21, P < 0.05) and an increase in
      fruit consumption was associated with a decrease in confusion (r = -0.26, P <
      0.05). CONCLUSION: In addition to the health benefits of a moderate-sodium
      Dietary Approaches to Stop Hypertension diet on blood pressure and bone health,
      this diet had a positive effect on improving mood in postmenopausal women.

PMID- 22480800
TI  - Adipose tissue volume is decreased in recently diagnosed cancer patients with
      cachexia.
AB  - OBJECTIVE: Approximately 50% of patients with cancer develop cachexia. The aim of
      the present study was to determine if there were differences in the amount of
      visceral and subcutaneous adipose tissues at the time of the diagnosis among
      patients with cancer cachexia (CC), patients with cancer and a stable weight
      (WS), and patients with cancer and weight loss because of gastrointestinal
      obstruction (GO). METHODS: Patients with recently diagnosed cancer were divided
      into the CC, WS, and GO groups. Body composition was determined by bioimpedance.
      Basal metabolic rate and energy expenditure were estimated by indirect
      calorimetry. Visceral and subcutaneous white adipose tissues (WATs) were
      quantified by the segmentation of a 10-mm-thick computed tomographic slice
      obtained through the central part of the third lumbar vertebra. RESULTS: The body
      mass index and body fat were decreased in the CC and GO groups compared with the
      WS group, but there were no significant differences between the two weight-losing
      groups. Lean body mass, total body water, and energy expenditure were similar
      among the groups. The visceral WAT volume was decreased in the CC but not in the
      GO group compared with the WS group (P < 0.05). The subcutaneous WAT was
      decreased in the CC and GO groups compared with the WS group (P < 0.001).
      CONCLUSION: The WAT was decreased in the CC and GO groups compared with the WS
      group. Furthermore, patients with CC exhibited a selective decrease in visceral
      WAT. This may be new information regarding the WAT distribution in CC.

PMID- 22480801
TI  - Novel phytonutrient contributors to antioxidant protection against cardiovascular
      disease.
AB  - The associations linking endothelial inflammation, endothelial oxidative stress,
      and atherogenesis and the potential for dietary phytonutrients to decrease the
      impact of these associations were assessed. A detailed literature review was
      conducted and summarized. A large body of scientific evidence describes the
      interactions among endothelial inflammation, endothelial oxidative stress, and
      atherogenesis. A growing body of research indicates that several dietary
      phytonutrients (astaxanthin, lycopene, lutein, and glabridin) can decrease the
      risk for atherosclerosis by decreasing endothelial inflammation and oxidative
      stress. The consumption of foods or dietary supplements that provide astaxanthin,
      lycopene, lutein, and glabridin can ameliorate endothelial inflammation and
      oxidative stress, retard atherogenesis, and decrease the risk for atherogenic
      cardiovascular disease.

PMID- 22480802
TI  - How efficient is the orienting of spatial attention to pain? An experimental
      investigation.
AB  - This study investigated how efficient spatial attention was oriented to pain in 2
      experiments. Participants detected whether painful (pain group) or nonpainful
      (control group) somatosensory stimuli were delivered to the left or right hand.
      Each stimulus was preceded by a visual cue presented near to the stimulated hand
      (valid trial), the opposite hand (invalid trial), or centrally between hands. To
      examine both exogenous and endogenous orienting of attention, the spatial
      predictability of somatosensory targets was manipulated. In the first experiment,
      visual cues were nonpredictive for the location of the pain stimulus, as a result
      of which, orienting was purely exogenous, i.e., resulting from the occurrence of
      the visual cue at the location of somatosensory input. In the second experiment,
      visual cues were spatially predictive, as a result of which, endogenous control
      was added, i.e., attention driven by expectations of where the somatosensory
      target will occur. The results showed that only in experiment 1 was spatial
      attention oriented more efficiently to painful compared with nonpainful
      somatosensory stimulation. This effect was due to faster responses on valid
      relative to baseline trials (engagement), rather than slower responses on invalid
      relative to baseline trials (disengagement), and was significantly correlated
      with self-reported bodily threat. In experiment 2, prioritization of the pain
      location was probably overridden by task strategies because it was advantageous
      for participants' task performance to attend to the cued location irrespective of
      whether stimulation was painful or not. Implications of these findings for
      theories of hypervigilance and attentional management of pain are discussed.

PMID- 22480803
TI  - Conditioned pain modulation predicts duloxetine efficacy in painful diabetic
      neuropathy.
AB  - This study aims to individualize the selection of drugs for neuropathic pain by
      examining the potential coupling of a given drug's mechanism of action with the
      patient's pain modulation pattern. The latter is assessed by the conditioned pain
      modulation (CPM) and temporal summation (TS) protocols. We hypothesized that
      patients with a malfunctioning pain modulation pattern, such as less efficient
      CPM, would benefit more from drugs augmenting descending inhibitory pain control
      than would patients with a normal modulation pattern of efficient CPM. Thirty
      patients with painful diabetic neuropathy received 1 week of placebo, 1 week of
      30 mg/d duloxetine, and 4 weeks of 60 mg/d duloxetine. Pain modulation was
      assessed psychophysically, both before and at the end of treatment. Patient
      assessment of drug efficacy, assessed weekly, was the study's primary outcome.
      Baseline CPM was found to be correlated with duloxetine efficacy (r=0.628,
      P<.001, efficient CPM is marked negative), such that less efficient CPM predicted
      efficacious use of duloxetine. Regression analysis (R(2)=0.673; P=.012) showed
      that drug efficacy was predicted only by CPM (P=.001) and not by pretreatment
      pain levels, neuropathy severity, depression level, or patient assessment of
      improvement by placebo. Furthermore, beyond its predictive value, the treatment
      induced improvement in CPM was correlated with drug efficacy (r=-0.411, P=.033).
      However, this improvement occurred only in patients with less efficient CPM
      (16.8+/-16.0 to -1.1+/-15.5, P<.050). No predictive role was found for TS. In
      conclusion, the coupling of CPM and duloxetine efficacy highlights the importance
      of pain pathophysiology in the clinical decision-making process. This evaluative
      approach promotes personalized pain therapy.

PMID- 22480804
TI  - The history of sleep medicine.
AB  - Sleep medicine as it is known today actually started as research and scientific
      study, not as clinical medicine. When one considers that sleep medicine today is
      in its infancy, it is obvious that there is much more to learn. The history of
      sleep dates back to the 1880s. However, the most significant developments that
      moved sleep forward into the practice of medicine, and eventually dentistry,
      occurred from the 1950s on. This article explores the highlights of the history
      of sleep and sleep medicine.

PMID- 22480805
TI  - Basic biology of sleep.
AB  - Sleep can be defined as a complex reversible state characterized by behavioral
      quiescence, diminished responsiveness to external stimuli, and a stereotypical
      species-specific posture. Both components of sleep, non-rapid eye movement and
      rapid eye movement, are generated and maintained by central nervous system
      networks that use specific neurotransmitters located in specific areas of the
      brain. Widespread changes in physiologic processes occur during sleep, and these
      changes may influence the presentation and severity of specific medical
      disorders.

PMID- 22480806
TI  - Screening and comprehensive evaluation for sleep related breathing disorders.
AB  - The dentist is well positioned to screen for patients at risk for a sleep
      disorders, most often a sleep related breathing disorder, and when adequately
      trained, can treat those diagnosed with sleep apnea using an oral appliance. This
      treatment requires some degree of training to be able to recognize the symptoms
      related to the more common sleep disorders. The dentist must determine if the
      patient is at risk for a sleep disorder through the use of screening
      questionnaires, reviewing the health history, and additional questioning of the
      patient.

PMID- 22480807
TI  - Cone beam computed tomography: craniofacial and airway analysis.
AB  - Imaging plays a role in the anatomic assessment of the airway and adjacent
      structures. This article discusses the use of 3-dimensional (3D) imaging (cone
      beam computed tomography [CBCT]) to evaluate the airway and selected regional
      anatomic variables that may contribute to obstructive sleep-disordered breathing
      (OSDB) in patients. CBCT technology uses a cone-shaped x-ray beam with a special
      image intensifier and a solid-state sensor or an amorphous silicon plate for
      capturing the image. Incorporation of 3D imaging into daily practice will allow
      practitioners to readily evaluate and screen patients for phenotypes associated
      with OSDB.

PMID- 22480808
TI  - Sleep study--what the dentist needs to know.
AB  - The intent of this article is to familiarize dental professionals with the
      polysomnogram (PSG). The evaluation of patients presenting with sleep disorders
      is complex, requiring an investigative approach that synthesizes information
      obtained through a detailed history, a focused physical examination, and
      appropriate confirmatory testing. The PSG is the only clinical tool that measures
      multiple physiologic variables to qualitatively and quantitatively evaluate
      sleep. A proper understanding of the role of the PSG and its measurements and
      interpretation allows for a proper diagnosis so as to provide an optimal range of
      treatments for individual patients.

PMID- 22480809
TI  - Medical disorders impacted by obstructive sleep apnea.
AB  - Normal-sleeping individuals experience a lower metabolic rate and relative
      cardiovascular quiescent state with lower heart rate and blood pressure that
      naturally occurs during sleep compared with the waking state. In patients with
      obstructive sleep apnea (OSA), this quiescent state becomes disrupted. Research
      has shown a higher risk for several medical disorders, most ominous being a
      myocardial infarction or stroke. This article serves as an overview to the
      cardiovascular, cerebrovascular, metabolic, and gastroesophageal effects of OSA.

PMID- 22480810
TI  - Sleep bruxism: a comprehensive overview for the dental clinician interested in
      sleep medicine.
AB  - Sleep bruxism (SB) is a common sleep-related motor disorder characterized by
      tooth grinding and clenching. SB diagnosis is made on history of tooth grinding
      and confirmed by polysomnographic recording of electromyographic (EMG) episodes
      in the masseter and temporalis muscles. The typical EMG activity pattern in
      patients with SB is known as rhythmic masticatory muscle activity (RMMA). The
      authors observed that most RMMA episodes occur in association with sleep arousal
      and are preceded by physiologic activation of the central nervous and sympathetic
      cardiac systems. This article provides a comprehensive review of the cause,
      pathophysiology, assessment, and management of SB.

PMID- 22480811
TI  - Temporomandibular disorder pain and dental treatment of obstructive sleep apnea.
AB  - Treatment of sleep apnea with mandibular advancement devices (MADs) may be
      associated with the development of symptoms of temporomandibular disorder (TMD).
      This article discusses the different types of TMD and orofacial pain problems
      that may occur during treatment of obstructive sleep apnea (OSA) with a MAD. It
      is critical that the general dentist who is providing dental devices for OSA
      perform a thorough physical and neurologic assessment of the temporomandibular
      joint and associated structures before providing such a device so that
      preexisting problems are identified and discussed with the patient.

PMID- 22480812
TI  - Effectiveness and outcome of oral appliance therapy.
AB  - Oral appliances (OAs) are a primary treatment option for snoring and mild to
      moderate obstructive sleep apnea (OSA) and are implemented as a noninvasive
      alternative for patients with severe OSA who are unwilling or unable to tolerate
      continuous positive airway pressure for the management of their disease. Studies
      have demonstrated the ability of OAs to eliminate or significantly reduce the
      symptoms of OSA and produce a measurable influence on the long-term health
      effects of the disease. Most studies have evaluated one type of OAs, the
      mandibular advancement splints. This article describes the effectiveness and
      outcomes of mandibular advancement splints.

PMID- 22480813
TI  - Use of portable monitoring for sleep-disordered breathing treated with an oral
      appliance.
AB  - The potential use of a portable monitor to assess the outcome of treatment with
      an oral appliance would ideally be performed by the dentist who is managing the
      patient's sleep-disordered breathing. Portable monitoring is one of the most cost
      effective ways to assess the response to the oral appliance, to determine if
      further adjustment to the appliance is needed, and to retest to determine the
      current status following any adjustment. This article emphasizes the use of
      portable monitors primarily for follow-up care and assessment as opposed to
      diagnosis or, as it is sometimes referred to, screening.

PMID- 22480814
TI  - Surgical reconstruction of the upper airway for obstructive sleep apnea.
AB  - Positive airway pressure can be effective for OSA treatment but is not
      effectively used by many patients. Surgical reconstruction of the airway is
      appropriate for patients who are not otherwise effectively treated or as first
      line treatment for patients with focal airway lesions. For surgical planning,
      examination schemes of the awake patient, as well as sleep endoscopy may be used.
      Nasal surgery may facilitate treatment using positive airway pressure or oral
      appliances or to improve quality of life. Pharyngoplasty and tongue base
      techniques for therapeutic upper airway reconstruction may be performed staged or
      simultaneously. Current and future approaches are described.

PMID- 22480815
TI  - Medical insurance for dental sleep medicine.
AB  - Over the last 5 to 7 years, dental teams have mastered the art and science of
      processing dental insurance for their patients but have major difficulties
      learning how to help their patients when it comes to medical insurance. This
      article attempts to provide a basic guide for the dental team in coding, billing,
      and processing of major medical insurance for dental sleep medicine. Although
      there is certainly a learning curve for the dental team in this endeavor, the
      "patient and physician friendly" dental sleep medicine practice is a model that
      will help to assure growth and success.

PMID- 22480816
TI  - Sleep medicine in dentistry.

PMID- 22480817
TI  - Insight into pattern of codon biasness and nucleotide base usage in serotonin
      receptor gene family from different mammalian species.
AB  - 5-HT (5-Hydroxy-tryptamine) or serotonin receptors are found both in central and
      peripheral nervous system as well as in non-neuronal tissues. In the animal and
      human nervous system, serotonin produces various functional effects through a
      variety of membrane bound receptors. In this study, we focus on 5-HT receptor
      family from different mammals and examined the factors that account for codon and
      nucleotide usage variation. A total of 110 homologous coding sequences from 11
      different mammalian species were analyzed using relative synonymous codon usage
      (RSCU), correspondence analysis (COA) and hierarchical cluster analysis together
      with nucleotide base usage frequency of chemically similar amino acid codons. The
      mean effective number of codon (ENc) value of 37.06 for 5-HT(6) shows very high
      codon bias within the family and may be due to high selective translational
      efficiency. The COA and Spearman's rank correlation reveals that the nucleotide
      compositional mutation bias as the major factors influencing the codon usage in
      serotonin receptor genes. The hierarchical cluster analysis suggests that gene
      function is another dominant factor that affects the codon usage bias, while
      species is a minor factor. Nucleotide base usage was reported using Goldman,
      Engelman, Stietz (GES) scale reveals the presence of high uracil (>45%) content
      at functionally important hydrophobic regions. Our in silico approach will
      certainly help for further investigations on critical inference on evolution,
      structure, function and gene expression aspects of 5-HT receptors family which
      are potential antipsychotic drug targets.

PMID- 22480818
TI  - Effect of escitalopram on hot flash interference: a randomized, controlled trial.
AB  - OBJECTIVE: To estimate the effect of escitalopram (10-20 mg/d) versus placebo for
      reducing hot flash interference in daily life and understand correlates and
      predictors of reductions in hot flash interference, a key measure of quality of
      life. DESIGN: Multisite, randomized, double-blind, placebo-controlled clinical
      trial. SETTING: MsFLASH clinical sites in Boston, Indianapolis, Oakland, and
      Philadelphia. PATIENT(S): A total of 205 midlife women (46% African-American) who
      met criteria participated. INTERVENTION(S): After baseline, women were randomized
      to one pill of escitalopram 10 mg/d (n = 104) or placebo (n = 101) with follow-up
      at 4 and 8 weeks. At week 4, those not achieving 50% fewer hot flashes were
      increased to two pills daily (20 mg/d or 2 placebo pills). MAIN OUTCOME
      MEASURE(S): The Hot Flash Related Daily Interference Scale; correlates were
      variables from hot flash diaries; predictors were baseline demographics, clinical
      variables, depression, anxiety, sleep quality, and hot flashes. RESULT(S):
      Compared to placebo, escitalopram significantly reduced hot flash interference by
      6.0 points at week 4 and 3.4 points at week 8 more than placebo. Reductions in
      hot flash interference correlated with changes in hot flash diary variables.
      However, baseline variables did not significantly predict reductions in hot flash
      interference. CONCLUSION(S): Escitalopram (10-20 mg/d) for 8 weeks improves
      women's quality of life and this benefit did not vary by demographic, clinical,
      mood, sleep, or hot flash variables. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT00894543.

PMID- 22480819
TI  - Birth defects in children conceived by in vitro fertilization and
      intracytoplasmic sperm injection: a meta-analysis.
AB  - OBJECTIVE: To conduct a meta-analysis of studies assessing the effect of IVF and
      intracytoplasmic sperm injection (ICSI) on birth defects. DESIGN: Meta-analysis.
      SETTING: Centers for reproductive care. PATIENT(S): Patients treated by IVF
      and/or ICSI. INTERVENTION(S): We identified all studies published by September
      2011 with data related to birth defects in children conceived by IVF and/or ICSI
      compared with spontaneously conceived children, or birth defects in the children
      conceived by IVF compared with those by ICSI. Risk ratios from individual studies
      were pooled with the fixed and random effect models. MAIN OUTCOME MEASURE(S):
      Risk of birth defects in children conceived by IVF and/or ICSI. RESULT(S): Of 925
      studies reviewed for eligibility, 802 were excluded after screening titles and
      abstracts, 67 were excluded for duplicated data, data unavailable, or
      inappropriate control group, 56 were included in the final analysis. Among the 56
      studies, 46 studies had data on birth defects in children conceived by IVF and/or
      ICSI (124,468) compared with spontaneously conceived children. These studies
      provided a pooled risk estimation of 1.37 (95% confidence interval [CI]: 1.26
      1.48), which is also evident in subgroup analysis. In addition, 24 studies had
      data on birth defects in children conceived by IVF (46,890) compared with those
      by ICSI (27,754), which provided an overall no risk difference. CONCLUSION(S):
      Children conceived by IVF and/or ICSI are at significantly increased risk for
      birth defects, and there is no risk difference between children conceived by IVF
      and/or ICSI.

PMID- 22480820
TI  - Gene and protein expression signature of endometrial glandular and stromal
      compartments during the window of implantation.
AB  - OBJECTIVE: To map the changes in messenger RNA (mRNA) and protein abundance
      during the window of implantation in specifically endometrial stromal and
      glandular epithelial cells obtained using laser microdissection microscopy (LDM).
      DESIGN: Endometrial samples were collected from two menstrual cycles at 2 and 7
      days after first significant rise in blood LH, and separate cell populations were
      obtained using LDM. A new generation linear polymerase chain reaction (PCR)
      amplified the mRNA, which were hybridized to both Affymetrix U133 Plus2 and
      Agilent 4x44K microarrays followed by gene set analysis. Immunohistochemistry
      assessed protein expression between the two collection times. SETTING: In vitro
      fertilization clinic. PATIENT(S): Nine Caucasian, fertile, cycling women.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycle dating using blood markers;
      microarrays on laser microdissected glands and stroma; dual platform microarray
      confirmation; immunohistochemical analysis of cell cycle proteins. RESULT(S): The
      two microarray platforms showed concordance. During the window of implantation, a
      statistically significant network of 22 mRNA associated with the cell cycle was
      down-regulated. Immunohistochemistry identified altered localization in stroma.
      CONCLUSION(S): Microarrays demonstrated glands and stroma have distinct mRNA
      signatures, each dependent on the day of the cycle. We characterized two
      compartments of the receptive endometrium with a transcriptomic signature
      identifying regulation of only the cell cycle. Immunohistochemical analysis of
      cell cycle proteins identified a signature staining pattern of nuclear
      relocalization of a group of cyclins of stromal cells, which may be clinically
      applicable.

PMID- 22480821
TI  - Full in vitro fertilization laboratory mechanization: toward robotic assisted
      reproduction?
AB  - OBJECTIVE: To describe the current efforts made to standardize different steps of
      assisted reproductive technology processes by the introduction of new
      technologies for the nonsubjective sperm selection process, oocyte denudation by
      mechanical removal of cumulus cells, oocyte positioning, sperm motility
      screening, fertilization, embryo culture, media replacement by microfluidics, and
      monitoring of embryo development by time-lapse photography, embryo secretions,
      and/or O(2) consumption. These technologies could be integrated in a unique and
      fully automated device. DESIGN: Pubmed database and research and development data
      from authors. SETTING: University-affiliated private center. PATIENT(S): None.
      INTERVENTION(S): None. MAIN OUTCOME MEASUREMENT(S): None. RESULT(S): Several
      technologies would be useful for: 1) selection of sperm based on viability; 2)
      manipulation and removal of the cumulus cells' narrow channel regions combined
      with microfluidics; 3) advances in oocyte positioning precision through the use
      of joystick-controlled micromanipulators; 4) microfluidics allowing the gradual
      change of a culture medium, which might result in better embryo development as
      well as reduce the amount of embryo manipulation; 5) time-lapse, proteomic, and
      metabolic scoring of the developing embryo, allowing multiple and optimized
      selection of the embryos. The technologies described in this review have not yet
      reported reliable clinical proofs. CONCLUSION(S): We already have available some
      of the technologies described, but we envisage an integrated device, i.e., an IVF
      lab-on-a-chip, by which oocyte and sperm would be processed to achieve a perfect
      embryo ready to be delivered into the uterus. With such a device, sample
      preparation, chemical or biologic reactions, and data collection would be
      integrated.

PMID- 22480822
TI  - Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and
      low-dose human chorionic gonadotropin to optimize live birth rates in high
      responders.
AB  - OBJECTIVE: To compare live birth rates after dual trigger of oocyte maturation
      with GnRH agonist (GnRHa) and low-dose hCG versus GnRHa alone in high responders
      with peak E(2) <4,000 pg/mL at risk of ovarian hyperstimulation syndrome (OHSS).
      DESIGN: Retrospective cohort study. SETTING: University-based tertiary-care
      fertility center. PATIENT(S): Patients <40 years old with peak E(2) <4,000 pg/mL
      at risk of OHSS who underwent IVF/intracytoplasmic sperm injection with GnRH
      antagonist protocol and triggered with GnRHa alone or GnRHa plus 1,000 IU hCG
      (dual trigger) for oocyte maturation. INTERVENTION(S): GnRHa alone versus dual
      trigger. MAIN OUTCOME MEASURE(S): Live birth, implantation, and clinical
      pregnancy rates and OHSS. RESULT(S): The dual-trigger group had a significantly
      higher live birth rate (52.9% vs. 30.9%), implantation rate (41.9% vs. 22.1%),
      and clinical pregnancy rate (58.8% vs. 36.8%) compared with the GnRHa trigger
      group. One case of mild OHSS occurred in the dual-trigger group, and there were
      no cases of OHSS in the GnRHa trigger group. CONCLUSION(S): Dual trigger of
      oocyte maturation with GnRHa and low-dose hCG in high responders with peak E(2)
      <4,000 pg/mL improves the probability of conception and live birth without
      increasing the risk of significant OHSS.

PMID- 22480823
TI  - Efficacy of treatment in older depressed patients: a systematic review and meta
      analysis of double-blind randomized controlled trials with antidepressants.
AB  - BACKGROUND: This systematic review evaluated all published double-blind,
      randomized controlled antidepressant trials (RCTs) of acute phase treatment of
      older depressed patients. METHODS: Meta-analyses were conducted in 51 double
      blind RCTs of antidepressants in older patients. The results were also compared
      with 29 double-blind RCTs that did not produce extractable data to enter the meta
      analysis. RESULTS: All classes of antidepressant (TCA's, SSRIs and other
      antidepressants) were more effective than placebo in achieving response. In
      achieving remission however, only pooling all 3 classes of antidepressants
      together showed a statistically significant difference from placebo. No
      differences were found in remission or response rates between classes of
      antidepressants. TCAs were also equally effective compared with SSRIs in
      achieving response in more severely depressed patients. The numbers needed to
      treat (NNT) were 14.4 (95% CI 8.3-50) for one additional remission to
      antidepressants compared with placebo and 6.7 (95% CI 4.8-10) for response. The
      results of the double-blind RCTs that did not produce extractable data to enter
      the meta-analysis were in concordance with the RCTs that were included in the
      meta-analysis. LIMITATIONS: Only 4 RCTs were found that have not been published.
      Few studies have focused on severely depressed older people. CONCLUSIONS:
      Antidepressant treatment in older depressed patients is efficacious. We could not
      demonstrate differences in effectiveness between different classes of
      antidepressants; this was also the case in more severely depressed patients.

PMID- 22480824
TI  - Phthalocyanine tetrasulfonates bind to multiple sites on natively-folded prion
      protein.
AB  - The phthalocyanine tetrasulfonates (PcTS), a class of cyclic tetrapyrroles, bind
      to the mammalian prion protein, PrP. Remarkably, they can act as anti-scrapie
      agents to prevent the formation and spread of infectious, misfolded PrP. While
      the effects of phthalocyanines on the diseased state have been investigated, the
      interaction between PcTS and PrP has not yet been extensively characterized. Here
      we use multiple, complementary assays (surface plasmon resonance, isothermal
      titration calorimetry, fluorescence correlation spectroscopy, and tryptophan
      fluorescence quenching) to characterize the binding of PcTS to natively-folded
      hamster PrP(90-232), in order to determine binding constants, ligand
      stoichiometry, influence of buffer ionic strength, and the effects of chelated
      metal ions. We found that binding strength depends strongly on chelated metal
      ions, with Al(3+)-PcTS binding the weakest and free-base PcTS the strongest of
      the three types tested (Al(3+), Zn(2+), and free-base). Buffer ionic strength
      also affected the binding, with K(d) increasing along with salt concentration.
      The binding isotherms indicated the presence of at least two different binding
      sites with micromolar affinities and a total stoichiometry of ~4-5 PcTS molecules
      per PrP molecule.

PMID- 22480826
TI  - Chromatin modifications, epigenetics, and how protozoan parasites regulate their
      lives.
AB  - Chromatin structure plays a vital role in epigenetic regulation of protozoan
      parasite gene expression. Epigenetic gene regulation impacts upon parasite
      virulence, differentiation and cell-cycle control. Recent work in many
      laboratories has elucidated the functions of proteins that regulate parasite gene
      expression by chemical modification of constituent nucleosomes. A major focus of
      investigation has been the characterization of post-translational modifications
      (PTMs) of histones and the identification of the enzymes responsible. Despite
      conserved features and specificity common to all eukaryotes, parasite enzymes
      involved in chromatin modification have unique functions that regulate unique
      aspects of parasite biology.

PMID- 22480828
TI  - Ischemic preconditioning reduces transplanted submandibular gland injury.
AB  - BACKGROUND: Ischemic preconditioning (IPC) can reduce ischemia/reperfusion (I/R)
      injury in multiple organs and species. However, the effect of IPC on transplanted
      submandibular glands remains unknown. We explored the protection of IPC in
      transplanted submandibular glands in the rabbit and the underlying mechanism.
      METHODS: IPC was performed by clamping the lingual artery for 10 min, with 10 min
      of reperfusion before transplantation. Male rabbits were randomly divided into
      control, transplantation, and IPC groups (n = 6 each). Saliva secretion,
      oxidative stress, pro-inflammatory cytokine levels, and apoptosis-related protein
      levels were determined at 1, 12, and 24 h after reperfusion. RESULTS: Salivary
      flow was significantly increased at 12 h and decreased at 24 h in the
      transplanted glands. IPC treatment prevented the reduced saliva secretion at 24 h
      after reperfusion (P < 0.01). The mRNA levels of tumor necrosis factor-alpha,
      interleukin-1beta, and reactive oxygen species, as well as malondialodehyde (MDA)
      and myeloperoxidase activity, were significantly increased and superoxide
      dismutase activity was decreased in the transplanted glands. However, these
      changes were all attenuated with IPC treatment (all P < 0.05). Also, acinar cell
      apoptosis and Bax protein expression were decreased and Bcl-2 protein expression
      was increased in the IPC-treated glands at 1 and 12 h after reperfusion (all P <
      0.05). CONCLUSIONS: IPC protects the secretory function of transplanted
      submandibular gland in the rabbit by reducing the inflammatory response,
      attenuating oxidative stress, and an anti-apoptosis process.

PMID- 22480827
TI  - Comparison of muscle force after immediate and delayed reinnervation using nerve
      muscle-endplate band grafting.
AB  - BACKGROUND: Because of poor functional outcomes of currently used reinnervation
      methods, we developed novel treatment strategy for the restoration of paralyzed
      muscles-the nerve-muscle-endplate band grafting (NMEG) technique. The graft was
      obtained from the sternohyoid muscle (donor) and implanted into the ipsilateral
      paralyzed sternomastoid (SM) muscle (recipient). METHODS: Rats were subjected to
      immediate or delayed (1 or 3 mo) reinnervation of the experimentally paralyzed SM
      muscles using the NMEG technique or the conventionally used nerve end-to-end
      anastomosis. The SM muscle at the opposite side served as a normal control.
      RESULTS: NMEG produced better recovery of muscle force as compared with end-to
      end anastomosis. A larger force produced by NMEG was most evident for small
      stimulation currents. CONCLUSIONS: The NMEG technique holds great potential for
      successful muscle reinnervation. We hypothesize that even better muscle
      reinnervation and functional recovery could be achieved with further improvement
      of the environment that favors axon-end plate connections and accelerates axonal
      growth and sprouting.

PMID- 22480829
TI  - Correcting the misnomers of epithelial-mesenchymal relations.

PMID- 22480830
TI  - Porcine intact and wounded skin responses to atmospheric nonthermal plasma.
AB  - Thermal plasma is a valued tool in surgery for its coagulative and ablative
      properties. We suggested through in vitro studies that nonthermal plasma can
      sterilize tissues, inactive pathogens, promote coagulation, and potentiate wound
      healing. The present research was undertaken to study acute toxicity in porcine
      skin tissues. We demonstrate that floating electrode-discharge barrier discharge
      (FE-DBD) nonthermal plasma is electrically safe to apply to living organisms for
      short periods. We investigated the effects of FE-DBD plasma on Yorkshire pigs on
      intact and wounded skin immediately after treatment or 24h posttreatment.
      Macroscopic or microscopic histological changes were identified using
      histological and immunohistochemical techniques. The changes were classified into
      four groups for intact skin: normal features, minimal changes or congestive
      changes, epidermal layer damage, and full burn and into three groups for wounded
      skin: normal, clot or scab, and full burn-like features. Immunohistochemical
      staining for laminin layer integrity showed compromise over time. A marker for
      double-stranded DNA breaks, gamma-H2AX, increased over plasma-exposure time.
      These findings identified a threshold for plasma exposure of up to 900s at low
      power and <120s at high power. Nonthermal FE-DBD plasma can be considered safe
      for future studies of external use under these threshold conditions for
      evaluation of sterilization, coagulation, and wound healing.

PMID- 22480831
TI  - Child-Turcotte score versus MELD for prognosis in a randomized controlled trial
      of emergency treatment of bleeding esophageal varices in cirrhosis.
AB  - BACKGROUND AND AIMS: Bleeding esophageal varices is responsible for much of the
      high mortality rate in cirrhosis. An important objective of management of
      bleeding varices is to develop reliable tools for predicting survival,
      controlling bleeding and encephalopathy, and improve quality of life. This study
      compared two widely used prognostic tools, the model for end-stage liver disease
      (MELD) and the Child-Turcotte (C-T) score, in a randomized controlled trial of
      emergency treatment of bleeding varices. METHODS: We randomized 211 unselected
      consecutive patients with cirrhosis and bleeding varices to endoscopic
      sclerotherapy (n = 106) or emergency portacaval shunt (n = 105). Diagnosis and
      treatment were accomplished within 20 hours. Follow-up was 100% for 10 y. We
      compared the prognostic powers of MELD and C-T upon entry, and then monthly for
      the first year and every 3 months thereafter. Statistical analysis included
      computation of receiver operating curves, the area under the curve, and the
      proportion of variability. RESULTS: In baseline determinations of MELD versus C
      T, there were no significant differences in predicting survival, recurrent
      encephalopathy, and rebleeding. The Child-Turcotte score was a stronger predictor
      than MELD of hospital readmissions and readmission days. In serial determinations
      over years, the prognostic power of both MELD and C-T was substantial, but C-T
      was significantly more effective in predicting survival and time to recurrent
      encephalopathy. CONCLUSIONS: In this first long-term comparison of MELD versus C
      T in cirrhosis with bleeding varices, C-T was consistently as effective as MELD
      in predicting survival, encephalopathy, rebleeding, hospital readmissions, and
      readmission days. In some measures, C-T was a more effective prognostic tool than
      MELD.

PMID- 22480832
TI  - Arginine vasopressin: the future of pressure-support resuscitation in hemorrhagic
      shock.
AB  - BACKGROUND: Arginine vasopressin (AVP) is a key player in maintaining the
      intravascular volume and pressure during hemorrhagic shock. During the past 2
      decades, animal studies, case reports, and reviews have documented the minimized
      blood loss and improved perfusion pressures in those receiving pressure support
      with AVP. MATERIALS AND METHODS: A PubMed search of studies was conducted with
      the terms: "AVP," "arginine vasopressin," "antidiuretic hormone," "hemorrhagic
      shock," "hemorrhage," "circulatory shock," "fluid resuscitation," "trauma,"
      "massive transfusion protocol," "physiology," "cerebral," "renal," "cardiac,"
      "perfusion," "dose," and "hypotension." The studies were located by a search of a
      combination of these terms. Also, within-PubMed citations relating to the studies
      gathered from the initial search were explored. Reports discussing vasopressin in
      hemorrhagic states were considered. No predetermined limit was used to choose or
      exclude articles. RESULTS: AVP is an important hormone in osmoregulation and
      blood pressure. During stress, such as hemorrhage, the levels have been shown to
      rapidly decrease. Furthermore numerous animal studies and limited human studies
      have shown that circulatory support with AVP is linked to improved outcomes. No
      large human prospective studies are available to guide its use at present, but
      some of its effectiveness seems to lie in its ability to increase calcium
      sensitivity in acidotic environs, thereby allowing for more effective maintenance
      of vascular tone than catecholamines. It also redirects blood from the periphery,
      creating a steal syndrome, and increases the oxygen supply to vital organs,
      minimizing blood loss, and allowing additional time for surgical repair.
      CONCLUSIONS: With these encouraging data, there is hope that "pressure support"
      will be the "resuscitation" considered necessary for a patient's optimum
      survival.

PMID- 22480833
TI  - Analysis of femoral artery intima-media thickness during the cardiac cycle.
AB  - BACKGROUND: Variations in the intima-media thickness (IMT) of the carotid artery
      during the cardiac cycle are well established. The change in femoral IMT during
      the cardiac cycle is largely unknown. This study focuses on the variation of
      femoral IMT, vessel diameter, and cross-sectional area (CSA) of the IMT during
      the cardiac cycle. METHODS: Video clips of the femoral artery were obtained using
      B-mode ultrasonography in 60 patients between the ages of 18 and 50. IMT and
      diameter measurements were made using automated software, and CSA was
      subsequently calculated. Triplicate measurements of each femoral artery were made
      at three points in the cardiac cycle: the R wave, the T wave, and at the point of
      maximal vessel diameter falling after the T wave and before the following P wave.
      RESULTS: Femoral IMT, diameter, and CSA did not show a statistically significant
      difference with measurement on the R versus the T wave (P>0.36, P>0.28, and
      P>0.76, respectively). Interestingly, when comparing measurements on the R or T
      wave with measurements taken at the maximum vessel diameter, there was a
      statistically significant difference in vessel diameter (P<0.001) and CSA
      (P<0.005) but not in femoral IMT (P>0.2). CONCLUSIONS: Unlike studies of the
      carotid artery, there were no statistically significant differences between
      measurements made at the R versus the T wave. There were, however, statistically
      significant differences noted in diameter and CSA when measurements were taken at
      a point later in the cardiac cycle. This has ramifications for future studies on
      vascular remodeling.

PMID- 22480834
TI  - Impact of different pancreatic microenvironments on improvement in hyperglycemia
      and insulin deficiency in diabetic rats after transplantation of allogeneic
      mesenchymal stromal cells.
AB  - BACKGROUND: Mesenchymal stromal cells (MSCs) in the pancreatic microenvironment
      can improve diabetes mellitus (DM). The aim of the present study was to determine
      whether different pancreatic microenvironments influence the improvement of
      hyperglycemia and insulin deficiency. METHODS: MSCs isolated from rat bone marrow
      were transplanted directly into different pancreatic microenvironments in male DM
      rats. DM was induced in the rats by streptozotocin injection. The rats were
      divided into 5 groups: normal control rats, DM control rats, and 3 experimental
      groups (DM rats plus MSCs injected into the head of the pancreas, the tail of the
      pancreas, or the whole pancreas). The body weight and blood glucose of the rats
      were monitored during the experiment after transplantation of the MSCs.
      Histopathologic and immunohistochemical analyses were used to detect the presence
      and number of islets and insulin production in the pancreatic tissue of the rats
      after MSC transplantation. RESULTS: At 28 days after MSC transplantation, we
      observed a statistically significant decrease in the blood glucose level and an
      increase in weight in DM rats compared with DM control rats (P < 0.0001 and P <
      0.03, respectively). A comparison of each of the DM rat groups treated with MSCs
      showed no significant differences in the blood glucose levels or body weight.
      CONCLUSION: Our results suggest that transplantation of MSCs could improve DM in
      the pancreatic microenvironment in an animal model with streptozotocin-induced
      DM. The different pancreatic areas into which the MSCs were implanted had no
      significant influence on the improvement in hyperglycemia and insulin deficiency.

PMID- 22480835
TI  - Cost-effectiveness of laparoscopic versus open pyloromyotomy.
AB  - BACKGROUND: Infantile hypertrophic pyloric stenosis can be corrected by either
      open (OP) or laparoscopic pyloromyotomy (LP). LP may provide clinical benefits of
      reduced time to postoperative full feeds and reduced postoperative inpatient
      stay, but the cost effectiveness is not known. Our aim was to compare the cost
      effectiveness of laparoscopic and open pyloromyotomy. METHODS: OP and LP were
      compared in a multicenter randomized double-blind controlled trial, for which the
      primary outcomes were time to full feeds and time to discharge. In order to
      undertake a detailed cost analysis, we assigned costs, calculated on an
      individual patient basis, to laboratory costs, imaging, medical staff,
      medication, ward, operative, and outpatient appointments for 74 patients
      recruited from one of the participating centers. Data (mean +/- SEM) were
      compared using linear regression analysis, adjusting for the minimization
      criteria used in the trial. RESULTS: Operation costs were similar between the two
      groups ($3,276 +/- $244 LP versus $3,535 +/- $152 OP). A shorter time to full
      feeds and shorter hospital stay in LP versus OP patients resulted in a highly
      significant difference in ward costs ($2,650 +/- $126 LP versus $3,398 +/- $126
      OP; P = .001) and a small difference in other costs. Overall, LP patients were
      $1,263 (95% confidence interval $395-$2,130; P = .005) less expensive to treat
      than OP patients. Sensitivity analyses of laparoscopic hardware usage and of
      incomplete pyloromyotomy indicated that LP was consistently less expensive than
      OP. CONCLUSIONS: LP is a cost-effective alternative to OP as it delivers improved
      clinical outcome at a lower price.

PMID- 22480836
TI  - Interaction between Kupffer cells and platelets in the early period of hepatic
      ischemia-reperfusion injury--an in vivo study.
AB  - BACKGROUND: Hepatic ischemia-reperfusion (I/R) leads to activation of Kupffer
      cells (KCs). The activated KCs cause platelet and leukocyte adhesion to the
      sinusoidal endothelium. Previously, we reported that platelet-endothelium
      interactions occur earlier than leukocyte responses. The aim of this study was to
      evaluate the interaction between platelets and KCs in the hepatic
      microcirculation after I/R. MATERIALS AND METHODS: Sprague-Dawley rats were
      divided into three groups: the no-ischemia group (control group; n = 6); the 20
      min ischemia group (I/R group; n = 6); and the 20-min ischemia + anti-rat
      platelet serum group (APS group; n = 6). KCs were labeled using the liposome
      entrapment method. The number of adherent platelets was observed for up to 120
      min after reperfusion by intravital microscopy. To investigate the effects of
      platelets on I/R injury, rats were injected intravenously with rabbit APS for
      platelet depletion. RESULTS: In the I/R group, the number of adherent platelets
      increased significantly after I/R. More than 50% of the adherent platelets
      adhered to KCs. Electron microscopy indicated that the platelets attached to the
      KCs after hepatic ischemia. The histologic findings indicated liver damage and
      apoptosis of hepatocytes in zone 1. In the I/R group, but not in the control and
      APS groups, serum ALT increased immediately after reperfusion. CONCLUSIONS: We
      succeeded in visualizing the dynamics of both KCs and platelets in the hepatic
      sinusoids. Liver ischemia induced the adhesion of platelets to KCs in the early
      period, which could play a key role in reperfusion injury of the liver.

PMID- 22480837
TI  - Rapamycin is less fibrogenic than Cyclosporin A as demonstrated in a rat model of
      chronic allograft nephropathy.
AB  - BACKGROUND: Cyclosporin A (CsA) is associated with significant chronic
      nephrotoxicity, which typically manifests as renal fibrosis. In contrast,
      rapamycin (RAPA) has been shown to inhibit fibrosis. This study sought to
      determine the effect of CsA and RAPA on the expression of connective tissue
      growth factor (CTGF) and E-cadherin in a rat kidney model of chronic allograft
      nephropathy. MATERIALS AND METHODS: Left renal grafts from male Fisher (F344,
      RT1(1v1)) rats were orthotopically transplanted into Lewis (LEW, RT1(1)) rats.
      After transplantation, all recipients were given CsA 10 mg/kg(-1) d(-1) for 10 d
      and divided into three groups (n = 9/group): (1) vehicle, administered orally;
      (2) CsA, 6 mg/kg(-1) d(-1); (3) RAPA, 0.8 mg/kg(-1) d(-1). At 4, 8, and 12 wk
      posttransplantation, the kidney allografts were harvested and serum creatinine
      levels were measured. Connective tissue growth factor expression was determined
      using real-time polymerase chain reaction and Western blot. Kidney allografts
      sections also underwent hematoxylin-eosin and Masson trichrome staining, in
      addition to CTGF and E-cadherin immunostaining. RESULTS: The serum creatinine
      levels were increased at 8 and 12 wk posttransplantation and were significantly
      lower in the RAPA group (P < 0.05). The Banff score also showed a significant
      decrease at 4, 8, and 12 wk (P < 0.05). CTGF messenger ribonucleic acid and
      protein levels were significantly lower in the RAPA group (P < 0.05), whereas E
      cadherin expression was higher in the RAPA group at 4, 8, and 12 wk (P < 0.05).
      Masson's trichrome staining showed a significant decrease in collagen deposition
      at 8 and 12 wk after RAPA treatment. CONCLUSION: RAPA can ameliorate fibrogenesis
      in kidney allografts by inhibiting epithelial-mesenchymal transition process,
      whereas CsA did not have this effect.

PMID- 22480838
TI  - IL-6, TNF-alpha, and iNOS is associated with decreased colonic contraction in
      rats with multiple organ dysfunction syndrome.
AB  - BACKGROUND: Gastrointestinal stasis is frequently accompanied by multiple organ
      dysfunction syndrome (MODS), which may lead to gastrointestinal smooth muscle
      dysfunction. The aim of this study is to investigate whether MODS initiates an
      inflammatory response and produces IL-6, TNF-alpha, and iNOS cytokines, as well
      as to determine whether these cytokines give rise to gastrointestinal smooth
      muscle dysfunction. MATERIALS AND METHODS: Sixty Wistar rats were divided equally
      into a negative control group, a positive control group, and a MODS group. The
      number of stool spots, the contractility of muscle strips in the colon, and
      morphologic changes to the colon smooth muscle were recorded. The mRNA and
      protein expressions of IL-6, TNF-alpha, and iNOS in the colon were detected by
      semiquantitative reverse transcription polymerase chain reaction and
      immunohistochemistry respectively. In addition, the NO level was observed.
      RESULTS: For the MODS group, the colon stool numbers, maximal contractive stress,
      and spontaneous frequency of muscle strips were, respectively, 0.77 +/- 0.52
      pill/h, 301g/cm(3), and 11.52 +/- 0.38 contractions/min (P < 0.05); for the
      negative control group, 1.54 +/- 0.64 pills/h, 645 g/cm(3), and 19.2 +/- 0.71
      contractions/min, respectively (P < 0.05); and for the positive control group,
      0.94 +/- 0.21 pills/h, 415 g/cm(3), and 14.1 +/- 0.52 contractions/min,
      respectively (P < 0.05). In the MODS group, there was a marked up-regulation of
      expression of IL-6, TNF-alpha, and iNOS and the contractility of the smooth
      muscle strips had a negative correlation with the expression of IL-6, TNF-alpha,
      and iNOS. CONCLUSION: We speculate that reduced colon motility in the MODS rats
      may be related to the increase in iNOS, IL-6, and TNF-alpha in the colon
      muscularis.

PMID- 22480839
TI  - Recovery from decompensated heart failure is associated with a distinct, phase
      dependent gene expression profile.
AB  - BACKGROUND: Clinical and experimental studies have traditionally focused on
      understanding the mechanisms for why a heart fails. We hypothesize that the
      pathways involved with myocardial recovery are not simply the reverse of those
      that cause heart failure. However, determining when and how a decompensated heart
      can recover remains unknown. METHODS: Male C57BL/6 mice underwent minimally
      invasive aortic banding for 3, 4, or 6 wk with or without subsequent band removal
      for 1 wk (debanding). Physiologic and genomic characterization was performed with
      intracardiac pressure-volume recordings, rt-PCR, and microarray analysis.
      RESULTS: Heart weight/body weight ratios and PV loops demonstrated a transition
      from compensated left ventricular hypertrophy to decompensated heart failure
      between 3 and 4 wk. Pressure-relief afforded by debanding allowed functional
      recovery and normalization of LVH after both 3 and 4, but not 6 wk of banding.
      Whole genome microarrays demonstrated 397 genes differentially expressed in
      recovered hearts, 250 genes differentially expressed in the nonrecoverable (6 wk)
      hearts, and only 10 genes shared by both processes. In particular, altered
      expression patterns of apoptotic and metalloproteinase genes correlated with the
      heart's ability to functionally recover. CONCLUSIONS: This clinically-relevant
      model (1) allows us to temporally and mechanistically characterize the failing
      heart, (2) demonstrates a unique genomic signature that may predict when a
      failing heart can recover following pressure relief, and (3) will prove useful as
      a template for testing therapeutic strategies aimed at recovery of the failing
      heart.

PMID- 22480840
TI  - Temporary rapid bowel ligation as a damage control adjunct improves survival in a
      hypothermic traumatic shock swine model with multiple bowel perforations.
AB  - BACKGROUND: Primary intestinal anastomosis is not the right choice for multiple
      bowel perforations under hemodynamically stable conditions. Our group has
      employed temporary rapid bowel ligation as a damage control procedure in a
      hypothermic traumatic shock swine model with multiple bowel perforations and
      hypothesized that damage control treatment would improve survival in the setting
      of a damage control surgery. MATERIALS AND METHODS: The abdomen was shot one time
      with an experimental modified gun while pigs were hemorrhaged to a mean arterial
      pressure of 40 mm Hg and maintained in shock for 40 min. Cold lactated Ringer
      solution was gradually infused to induce hypothermia. Animals were randomized to
      control (no resuscitation), primary anastomosis (PA), or temporary rapid bowel
      ligation (damage control group, DC). Animals were resuscitated for 12 h with the
      shed blood and lactated Ringer solution. Delayed anastomosis was performed in DC
      animals after resuscitation. Surviving animals were humanely killed 24 h after
      operation. Systemic hemodynamic parameters were recorded and blood samples were
      obtained for biochemical assays. The lung and ileum was harvested at the end of
      the experiment for pathologic evaluation and test of wet/dry weight ratio, TNF
      alpha level, and nuclear factor-kappaB activations. RESULTS: All animals suffered
      extreme physiologic conditions: hypothermia, severe acidosis, hypotension, and
      depressed cardiac output. Control animals suffered 100% mortality. Compared with
      the PA group, DC animals required less resuscitation fluid, normalized lactate
      levels faster, had lower serum creatine kinase, aspartate amino transferase
      levels and tissue TNF-alpha level and nuclear factor-kappaB activations, suffered
      less severe histopathology, had greater early survival. CONCLUSIONS: Multiple
      bowel perforations under hemodynamically stable conditions seem better managed
      with DC than with PA. Temporary rapid bowel ligation as a damage control adjunct
      is important to rapid control of multiple bowel perforations instead of a
      prolonged operative time.

PMID- 22480841
TI  - Porcine model of hemorrhagic shock with microdialysis monitoring.
AB  - BACKGROUND: A number of experimental protocols have been used to try to reproduce
      the clinical scenarios of hemorrhagic shock. The present study reports on an
      experimental swine model of controlled hemorrhagic shock that incorporates
      microdialysis monitoring for the evaluation of tissue perfusion and oxygenation.
      The aim of our study was to provide a reproducible, accurate, and reliable model
      for the testing and evaluation of therapeutic interventions in the area of
      hemorrhagic shock. METHODS: Landrace swine (n = 8) were subjected to controlled
      hemorrhagic shock, with a mean arterial pressure of 35 +/- 5 as the endpoint. Six
      more pigs were used as the control group. Microdialysis monitoring of the tissue
      lactate/pyruvate ratio was used. The mean arterial pressure, heart rate,
      hematocrit, hemoglobin, and lactate/pyruvate ratio measurements were obtained
      just before (phase A) and 30 min after (phase B) hemorrhage in the study group;
      the control group underwent the same measurements at the corresponding points.
      RESULTS: The mean arterial pressure, hematocrit, and hemoglobin were lower (P <
      0.05) in the study group than in the control group at phase B and compared with
      the values for the study group at phase A. Also, the lactate/pyruvate ratio and
      heart rate were greater (P < 0.05) in the study group than in control group at
      phase B and compared with the values for the study group at phase A. CONCLUSIONS:
      This model of hemorrhagic shock is effective and correlates with the clinical
      parameters of tissue oxygenation, as documented by microdialysis.

PMID- 22480842
TI  - Blockade of chloride ion transport enhances the cytocidal effect of hypotonic
      solution in gastric cancer cells.

PMID- 22480843
TI  - Utility of micro-ribonucleic acid profile for predicting recurrence of rectal
      cancer.
AB  - BACKGROUND: In early-stage rectal cancer, the surgeon must decide between the
      high morbidity of radical surgery and the high recurrence rates of local
      excision. A prognostic marker could improve patient selection and lower
      recurrence rates. Micro-ribonucleic acids (miRNAs), small RNAs that often inhibit
      tumor suppressors, have shown prognostic potential in colorectal cancer. We
      hypothesized that high miRNA levels in malignant tissue from early-stage rectal
      cancer patients could predict recurrence after local excision. MATERIALS AND
      METHODS: We identified 17 early-stage rectal cancer patients treated with local
      excision between 1990 and 2005, four of whom had recurrences. Total RNA was
      extracted from benign and malignant tissue and used in quantitative real-time
      reverse transcriptase polymerase chain reaction to probe for miR-20a, miR-21, miR
      106a, miR-181b, and miR-203. MiRNA data were evaluated for association with
      recurrence using univariate analysis with Wilcoxon rank sum test. RESULTS:
      Malignant tissue in both patients who had recurrences and patients who did not
      have recurrences had equivalently high levels of miRNA. However, the benign
      tissue of patients who recurred contained significantly higher levels of all five
      miRNAs when compared with the benign tissue of nonrecurrent patients despite
      having no histological differences. CONCLUSIONS: This is the first study to show
      that high miRNA levels of histologically benign tissue obtained from the surgical
      margin of locally excised rectal cancers can predict recurrence. The malignant
      miRNA levels did not have predictive value. Further investigation of miRNAs is
      needed to explore their potential for a more accurate prognosis of rectal cancer.

PMID- 22480844
TI  - A comparison of hematologic toxicity profiles after heated intraperitoneal
      chemotherapy with oxaliplatin and mitomycin C.
AB  - BACKGROUND: Although peritoneal carcinomatosis (PC) from colorectal and
      appendiceal tumors is consistent with metastatic disease, complete cytoreduction
      with hyperthermic intraperitoneal chemotherapy (HIPEC) using mitomycin C (MMC)
      can improve survival. A recent phase I study by our group using hyperthermic
      intraperitoneal oxaliplatin has demonstrated its safety and appropriate dose. Our
      goal in this study is to present a single institution's experience with the
      hematologic toxicities of the two agents. METHODS: We performed a retrospective
      review of 187 patients with PC of colorectal or appendiceal origin who underwent
      HIPEC with MMC or oxaliplatin between October 2006 and September 2009.
      Hematologic toxicities were graded according to the NCI Common Terminology
      Criteria for Adverse Events Version 4.0. RESULTS: Of the 187 patients, 55 had
      oxaliplatin-based HIPEC while 132 patients received MMC. Splenectomy was
      performed in 95 patients (50.8%) due to disease involvement. When comparing
      hematologic toxicity for MMC and oxaliplatin among the cohort of patients who
      underwent splenectomy, a statistically significant difference was noted in the
      incidence of platelet (P = .02) and neutrophil (P = .05) toxicity, with
      oxaliplatin having a higher incidence of grade 3 and grade 4 platelet and
      neutrophil toxicity respectively. However, no statistically significant
      difference in hematologic toxicity was noted between the two agents in patients
      who did not undergo splenectomy during cytoreductive surgery. CONCLUSIONS:
      Oxaliplatin-based HIPEC for PC of colorectal and appendiceal origin is associated
      with similar white blood cell toxicity and higher platelet and neutrophil
      toxicity compared to MMC-based HIPEC.

PMID- 22480845
TI  - Role of S-1-P receptors and human vascular smooth muscle cell migration in
      diabetes and metabolic syndrome.
AB  - BACKGROUND: Sphingosine-1-phosphate (S-1-P) is a bioactive sphingolipid released
      from activated platelets that stimulates migration of vascular smooth muscle
      cells (VSMC) in vitro. S-1-P is associated with oxidized low-density lipoprotein
      (oxLDL) and is important in vessel remodeling. S-1-P will activate multiple G
      protein-coupled receptors (S-1-PR 1 to 5), which can regulate multiple cellular
      functions, including cell migration. The aim of this study is to examine the role
      of S-1-PR signaling during smooth muscle cell migration in response to S-1-P.
      METHODS: Human VSMCs were cultured in vitro. Expression of S-1-PR 1 to 5 was
      determined in conditions mirroring diabetes (40 mM glucose) and metabolic
      syndrome (25 mM glucose with 20 MUM linoleic acid and 20 MUM oleic acid). Linear
      wound and Boyden microchemotaxis assays of migration were performed in the
      presence of S-1-P with and without siRNA against S-1-PR 1 to 5. Assays were
      performed for activation of ERK1/2, p38(MAPK) and JNK. RESULTS: Human VSMCs
      express S-1-PR1, S-1-PR2, and S-1-PR3. There was no significant expression of S-1
      PR4 and S-1-PR5. The expression of S-1-PR1 and S-1-PR3 is enhanced under high
      glucose conditions and metabolic syndrome conditions. Migration of VSMC in
      response to S-1-P is enhanced 2-fold by diabetes and 4-fold by metabolic
      syndrome. In diabetes, S-1-PR1 expression is enhanced, while S-1-PR2 and S-1-PR3
      expression are both maintained. In metabolic syndrome, S-1-PR1 and 3 expressions
      are enhanced and that of S-1-PR2 is reduced. siRNA to S-1-PR1 results in a 2-fold
      reduction in S-1-P-mediated cell migration under all conditions. siRNA to S-1-PR2
      enhanced cell migration only under normal conditions, while siRNA S-1-PR3
      decreased migration in metabolic syndrome only. Down-regulation of S-1-PR1
      reduced ERK1/2 activation in response to S-1-P, while that of S-1-PR2 had no
      effect under normal conditions. In diabetes, down-regulation of S-1-PR1 reduced
      activation of all three MAPKs. In metabolic syndrome, down-regulation of S-1-PR1
      and S-1-PR3 reduced activation of all three MAPKs. CONCLUSION: S-1-PR 1, 2, and 3
      regulate human VSMC migration and their expression level and function are
      modulated by conditions simulating diabetes and metabolic syndrome.

PMID- 22480846
TI  - Pro-domain in precursor nerve growth factor mediates cell death.
AB  - Nerve growth factor (NGF) is synthesized as a precursor, proNGF that undergoes
      post-translational processing to generate the biologically active mature NGF.
      While the neurotrophic function of NGF is well established, the activity of the
      proNGF precursor is still unclear. In this study, we have cloned the pro-domain
      of the precursor NGF molecule and have elucidated its function. We have used both
      mature and the furin resistant pro((R/G))NGF as controls in our experiments. Both
      pro((R/G))NGF and mature NGF (NGF) exhibited neurotrophic activity on PC12 cells
      while the pro-domain itself promoted cell death. The pro-domain, has been found
      to mediate apoptosis possibly by promoting the formation of a signaling complex
      comprising of endogenous p75(NTR) receptor, Bim/Bcl2 group of proteins and JNK
      and MEK1/2 signaling pathways.

PMID- 22480847
TI  - The potential of multi-slice computed tomography based quantification of the
      structural anisotropy of vertebral trabecular bone.
AB  - In the present paper we addressed the problem of whether the information about
      the structural anisotropy of trabecular bone can be retrieved from low-quality
      data, captured with clinical multi-raw spiral CT scanners. Two measures of
      quantifying structural anisotropy were tested - the current standard mean
      intercept length (MIL) and the gray-level structure tensor (GST). Thirty two
      vertebral bodies were MUCT and CT scanned. The reference values of structural
      anisotropy were measured in MUCT images and compared with the measures of
      structural anisotropy determined from low-quality CT data. MIL-based measures of
      structural anisotropy cannot be reliably determined from CT data. The assessment
      of the GST is significantly better than that of MIL, but the accuracy is not, in
      general, satisfactory. Based on the results of experiments with artificial data
      and the analysis of the real images, it can be concluded that a possible reason
      of the poor performance is anisotropic resolution of clinical CT scanners.

PMID- 22480848
TI  - Synthesis, biological evaluation, and molecular docking studies of benzyl, alkyl
      and glycosyl [2-(arylamino)-4,4-dimethyl-6-oxo-cyclohex-1-ene]carbodithioates, as
      potential immunomodulatory and immunosuppressive agents.
AB  - The immunomodulating properties of functionalized [2-(arylamino)-4,4-dimethyl-6
      oxo-cyclohex-1-ene] carbodithioates and 6,6-dimethyl-4-(2-(propan-2
      ylidene)hydrazinyl)-6,7-dihydro-2H-indazole-3(5H)-thione compounds have been
      investigated. Four of them, 13, 18, 19 and 20 inhibited PBMC proliferation
      induced by phytohemagglutinin (PHA) in a dose dependent manner with an IC(50) of
      <= 20 MUM. The Th-1 cytokine, interleukin-2 (IL-2) in PHA/PMA-stimulated
      peripheral blood mononuclear cells (PBMCs) is significantly inhibited by 13, 19
      and 20 with an IC(50) of 8.4 +/- 0.4, 5.34 +/- 0.15 and 4.9 +/- 0.7 MUM,
      respectively. They also inhibited the PMA/lipopolysaccharide-induced
      proinflammatory cytokines, IL-1beta and TNF-alpha production in human monocytic
      leukemia cells (THP-1), by 86%, 46% and 59.2% for IL-1beta and by 83.8%, 48.2%
      and 58.7% for TNF-alpha, respectively. Only 20 showed significant suppressive
      activity against the phagocyte oxidative burst in a dose dependent manner, with
      an IC(50) of 23.8 MUM. LPS-induced nitrites in mouse macrophages were found to be
      inhibited by compounds 6, 8, 13-15 and 19 with an IC(50), which range between 7.7
      and 63 MUM. The cytotoxicity for the active compounds was also studied on Rat
      Wistar Hepatocyte cell line, CC1 and the Mouse Fibroblast cell line 3T3 NIH in
      the presence of compounds using a standard MTT assay. Furthermore, structural
      activity relationship using automated docking software revealed that active
      compounds 7, 13 and 19, adapted the same binding mode, however the most active
      compound 20 is found deeply inserted within the ligand binding site of IL-2, as
      multiple hydrophobic and hydrophilic key interactions stabilize the compound
      inside the binding site, thus contributing higher activity.

PMID- 22480850
TI  - Synthesis, biological activity and docking study of imidazol-5-one as novel non
      nucleoside HIV-1 reverse transcriptase inhibitors.
AB  - A novel series of substituted imidazol-5-ones were designed, synthesized and
      evaluated for in vitro reverse transcriptase (RT) inhibition activity using
      reverse transcriptase assay kit (Roche, Colorimetric). It has been observed from
      in vitro screening that newly synthesized compounds possess RT inhibitory
      activity. Docking study was performed to study the binding orientation and
      affinity of synthesized compounds for RT enzyme.

PMID- 22480849
TI  - Structural modifications modulate stability of glutathione-activated arylated
      diazeniumdiolate prodrugs.
AB  - JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently
      in late pre-clinical development as an anti-cancer drug candidate. This prodrug
      was designed to be activated by glutathione (GSH) to release NO. To increase the
      potency of JS-K, we are investigating the effect of slowing the reaction of the
      prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s)
      by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues
      on GSH activation and the drugs' biological activity. We show that nitro-to-cyano
      substitution increases the half-life of the prodrug in the presence of GSH
      without compromising the compound's in vivo antitumor activity.

PMID- 22480851
TI  - Discovery of novel 2-piperidinol-3-(arylsulfonyl)quinoxalines as phosphoinositide
      3-kinase alpha (PI3Kalpha) inhibitors.
AB  - A series of novel 2-aliphatic cyclic amine-3-(arylsulfonyl)quinoxalines was
      synthesized based on the structural features of a previously identified lead,
      WR1. The 2-piperidinol-3-(arylsulfonyl)quinoxalines, which showed excellent
      antitumor activities against five human cell lines, with inhibitory activities
      ranging from 0.34 to 2.32 MUM, proved to be a promising class of novel PI3Kalpha
      inhibitors. The most potent compound 10d (WR23) showed an inhibitory IC(50) value
      of 0.025MUM against PI3Kalpha and significant pAkt suppression effect. Molecular
      docking analysis was performed to determine possible binding modes between
      PI3Kalpha and target compounds.

PMID- 22480852
TI  - Synthesis and biological evaluation of truncated alpha-galactosylceramide
      derivatives focusing on cytokine induction profile.
AB  - A series of truncated analogs of alpha-galactosylceramide with altered ceramide
      moiety was prepared, and evaluated for Th2-biased response in the context of IL
      4/IFN-gamma ratio. Phytosphingosine-modified analogs including cyclic, aromatic
      and ethereal compounds as well as the C-glycoside analog of OCH (2) with their
      cytokine inducing profile are disclosed.

PMID- 22480853
TI  - [Closing conference of the 1st day: Fighting against rare diseases: a priority
      for Eurobiomed, Biocluster of Southern, France].

PMID- 22480854
TI  - [End of life non-therapeutic intensive care for organ preservation and donation:
      legal and ethical issues].
AB  - INTRODUCTION: Stroke is presently the first cause of brain death in France. In
      this context, the question of elective non-therapeutic ventilation and
      resuscitation arises, aiming at enabling the patients for whom a decision to stop
      all the therapeutics has been made to evolve towards brain death and organ
      donation. In 2010, the French society of intensive care has released guidelines
      regarding stroke management including strategy on this topic. The question has
      also been referred to the Ethics Committee of Nancy university hospital by a
      chief-nurse of our hospital and we report here its conclusions and propositions.
      METHOD: A workgroup was appointed and has tackled the major issues: the
      justification, the risks for the patient and the society, the expression of the
      patient's consent, the legality of this care benefiting only a third party, and
      the practical details. CONCLUSIONS AND PROPOSITIONS: Elective intensive care
      following decision to stop any treatment after severe stroke seems to be
      justified with regard to public health as well as individual or collective
      ethics, providing the patient has expressed his/her consent or his/her non
      opposition before stroke occurrence. In France there is no legal frame regulating
      this practice, no information of the general public, and a public debate has yet
      to be initiated. Regarding the practical details, a priori agreement of the organ
      procurement organisation, patient's consent, and approval of the consultant
      required by the law of April 22, 2005 relating to Patients' rights and to the end
      of life to rule out any conflict of interest, have to be checked before referring
      the patient to ICU. Advance directives drafting must be developed and their scope
      extended to organ donation and elective resuscitation. Therefore, fair
      information of the general public and clarity and transparency of the procedures
      are needed. The prolongation of the French moratorium on Maastricht III type non
      heart beating organ donation - grounded on fears of possible conflicts on
      interest - seems obsolete with regard to the increasing respect of the patient's
      autonomy and to the risk of harmfulness entailed by elective resuscitation before
      death.

PMID- 22480855
TI  - [Conclusions of RARE 2011 and prospects for RARE 2013].

PMID- 22480856
TI  - [An organized network for patients after a stroke].

PMID- 22480857
TI  - [Myasthenia gravis associated to Biermer's disease].

PMID- 22480858
TI  - [Malignant degeneration of ovarian dermoid cyst].

PMID- 22480859
TI  - [Abstinence in alcohol-dependence: critical and updated approach of the 2001
      national guidelines].
AB  - 2001 French guidelines on the modalities of post-detoxification care for alcohol
      dependent patients recommend life-long abstinence from alcohol. Though experts of
      this conference have used a methodological tool based on the analysis of the
      literature for each specific issue, the recommended goal of abstinence only
      follows from expert advice and does not seem to be evaluated with the
      aforementioned methodological tool. Moreover, from 2001, several scientific works
      of higher level of evidence than expert advice show that a small but significant
      proportion of alcohol-dependent patients could maintain non-problematic drinking
      stably in time. The outcome discrepancies between patients could result from
      social, clinical and biological factors. Today, it seems necessary not to
      consider alcohol-dependent patients as a homogeneous population anymore, but on
      the contrary to delimit subgroups with different outcome profiles. Better
      knowledge about these subgroups of patients could allow the diversifying and
      personalising of care schemes, including in some cases temporary abstinence or
      controlled-drinking patterns.

PMID- 22480860
TI  - [The industrial future small batches].

PMID- 22480861
TI  - [Orthostatic hypotension: marker of severity and management of antihypertensive
      treatment].
AB  - Orthostatic Hypotension (OH) is an independent predictor of cardiovascular
      disease and of all-cause mortality. It is a marker of poor prognosis in older and
      middle-aged patients. It should be primarily sought, at diagnosis of
      hypertension, at therapeutic modification, and when suspected by symptoms. One
      must make therapeutic decisions in older patients, based on measured blood
      pressure in standing position. Before blaming the antihypertensive treatment, one
      must search for other contexts favoring orthostatic hypotension. The
      antihypertensive treatment in older patients should: be initiated with low
      dosages and subsequent dose titration, be associated to lifestyle changes, not be
      associated to medications that have the potential to induce Orthostatic
      Hypotension, include a clear information about Orthostatic Hypotension
      (recognition, preventive measures...).

PMID- 22480862
TI  - Drug-drug interactions and cooperative effects detected in electrochemically
      driven human cytochrome P450 3A4.
AB  - Inhibition of cytochrome P450-mediated drug metabolism by a concomitantly
      administered second drug is one of the major causes of drug-drug interactions in
      humans. The present study reports on the first electrochemically-driven drug-drug
      interactions of human cytochrome P450 3A4 probed with erythromycin, ketoconazole,
      cimetidine, diclofenac and quinidine. Cytochrome P450 3A4 was immobilized on
      glassy carbon electrodes in the presence of a cationic polyelectrolyte, PDDA
      (poly(diallyldimethylammonium chloride)). Inhibition of the turnover of its
      substrate, erythromycin, was subsequently measured using chronoamperometry at
      increasing concentrations of different known inhibitors of this enzyme namely
      ketoconazole, cimetidine and diclofenac for which IC(50) values of 135 nM, 80 MUM
      and 311 MUM were measured, respectively. Furthermore, heterotrophic cooperativity
      where the turnover of a first substrate is enhanced in the presence of a second
      one, was tested for the immobilized P450 3A4 enzyme. In this case, diclofenac 5
      hydroxylation was stimulated by the presence of quinidine resulting in doubling
      of the potency of this inhibitor i.e. lowering the measured IC(50) of diclofenac
      from 311 MUM down to 157 MUM. The results obtained in this work confirm that
      bioelectrochemistry can be employed for in vitro studies of not only drug-drug
      interactions but also prediction of adverse drug reactions in this important P450
      isozyme.

PMID- 22480863
TI  - Effects of a preoperative simplified home rehabilitation education program on
      length of stay of total knee arthroplasty patients.
AB  - In patients with severe knee osteoarthritis (OA), total knee arthroplasty (TKA)
      is performed for both symptom relief and to achieve better function in daily
      life. Implementation of efficient TKA rehabilitation programs with shorter length
      of stay (LOS) and reduced medical expenditures is an important issue in clinical
      practice. However, the effectiveness of preoperative rehabilitation programs is
      still under debate. Most preoperative rehabilitation programs last many weeks and
      may be more expensive than TKA. The purpose of this study was to investigate the
      effects of a simplified, easy-to-learn, and less time-consuming preoperative
      rehabilitation education program on TKA patients. PATIENTS AND METHODS: In this
      randomized controlled study, we allocated all the patients into study and control
      group according to chart number. The study group, which comprised 126 patients,
      participated in a 40-min preoperative home rehabilitation education program 4
      weeks prior to TKA. One hundred seventeen patients in the control group did not
      participate in this preoperative program. RESULTS: The study group required a
      shorter hospital LOS (mean: 7.12 days; P=0.027) and had less hospitalization
      related medical expenditures (mean: 123726 New Taiwan dollars [NTD], equivalent
      to 4266.4 United States dollars [USD] or 3022.1 [Euros]), (P=0.001) than the
      control group. However, the study group showed no significant improvement in
      function when compared to the control group. DISCUSSION: Our study demonstrates
      that a simplified preoperative rehabilitation program can reduce LOS and increase
      cost savings. This program was recommended as a routine protocol for OA patients
      before admission for TKA.

PMID- 22480864
TI  - Isolated anterior unilateral sacroiliac dislocation without pubic arch
      disjunction.
AB  - Sacroiliac joint dislocations frequently occur in a context of high-energy
      polytrauma. When there is disruption of the pelvic ring, sacroiliac joint
      displacements are more often posterior and combine two lesions: either lesions of
      the pubic arch as well as the posterior arch or bilateral lesions. The case we
      report here lacks these two characteristics. This is an isolated unilateral
      sacroiliac dislocation with no opening lesion of the pubic symphysis or fracture
      of ilio- or ischiopubic rami and with anterosuperior displacement. After
      emergency reduction of the dislocation, the secondary fixation was not performed,
      due to initial hemodynamic instability compounded by deteriorating central
      nervous system condition.

PMID- 22480865
TI  - One-year prospective comparative study of three large-diameter metal-on-metal
      total hip prostheses: serum metal ion levels and clinical outcomes.
AB  - INTRODUCTION: The good clinical outcomes and low wear obtained with 28-mm metal
      on-metal implants for total hip replacement prompted the development of large
      diameter heads that more closely replicated the normal hip anatomy, with the goal
      of improving prosthesis stability. However, the blood release of metal ions due
      to wear at the bearing surfaces and the high rate of groin pain seen with large
      diameter implants are causing concern. To determine whether these events are
      related to the geometry and metal composition of the prosthesis components, we
      conducted a prospective study of clinical outcomes and serum chromium and cobalt
      levels 1 year after implantation of three different acetabular cups. HYPOTHESIS:
      Serum levels of metal ions are comparable with different types of large-diameter
      metal-on-metal total hip prostheses. PATIENTS AND METHODS: We compared 24 DuromTM
      cups (D), 23 M2a MagnumTM cups (M2a), and 20 Conserve TotalTM (C) cups regarding
      serum chromium and cobalt levels, Postel-Merle d'Aubigne (PMA) scores and Oxford
      Hip Scores (OHS), as well as radiographic cup orientation and position at 1-year
      follow-up. Mean age was 66 years (45-85 years), mean body mass index was 28
      Kg/m(2) (18-45), patients were almost equally divided between males and females,
      and the reason for hip replacement was primary hip osteoarthritis in 65 patients
      and avascular necrosis in two. Metal ions were assayed in serum from blood drawn
      through non-metallic catheters, using mass spectrometry. RESULTS: Dislocation
      occurred in two patients (one D and one M2a) and revision to change the bearing
      couple was required in two patients in the D group. Serum cobalt levels in the C
      group were significantly higher (P=0. 0003) than in the two other groups (7.5
      MUg/L versus 2. 7 MUg/L with D and 2. 2 MUg/L with M2a). Clinical outcomes were
      better in the M2a group (PMA, 17.7 [16-18]; and OHS, 15.2 [12-30]; P<0.05). The
      PMA score and OHS were 17.5 (16-18) and 18.2 (12-42), respectively, with D; and
      16.75 (10-18) and 22. 2 (12-42), respectively, with C cups. When all three cup
      models were pooled, serum ion levels were higher in patients with pain than
      without pain (chromium, 7.1 MUg/L versus 2.1 MUg/L [P=0.002], and cobalt, 8 MUg/L
      versus 2.6 MUg/L [P=0.0004]). DISCUSSION: Serum chrome and cobalt levels
      increased after metal-on-metal total hip replacement, and the increase was
      greater with large-diameter implants than previously reported with 28-mm
      implants. Persistent pain was significantly associated with higher metal ion
      levels, with a probable cobalt cut-off of about 8 MUg/L. Differences in modular
      head-neck concepts may explain the observed variations.

PMID- 22480866
TI  - Meiotic double strand breaks repair in sexually reproducing eukaryotes: we are
      not all equal.

PMID- 22480868
TI  - IFN-alpha and TRAIL: a double edge sword in HIV-1 disease?
AB  - IFN-alpha is rapidly upregulated in response to viral infections and it is an
      essential player in innate immunity against viruses. pDCs are the most potent IFN
      alpha-producing cells and serve as an essential link between innate and adaptive
      immunity. The fate of pDCs in the course of HIV-1 infection is still a matter of
      debate, and the question of the detrimental role of chronic production of IFN
      alpha remains open. In particular, IFN-alpha has been shown to induce the
      expression of the death ligand TRAIL on pDCs, transforming them into killer pDCs
      that may contribute to the destruction of CD4(+) T cells, the hallmark of HIV-1
      induced disease. In this review, we discuss our current understanding of the
      protective and pathogenic roles of both IFN-alpha and TRAIL in HIV-1 disease.

PMID- 22480867
TI  - The metabolism beyond programmed cell death in yeast.
AB  - A cell's reaction to any change in the endogenous or exogenous conditions often
      involves a complex response that eventually either leads to cell adaptation and
      survival or to the initiation and execution of (programmed) cell death. The
      molecular decision whether to live or die, while depending on a cell's genome, is
      fundamentally influenced by its actual metabolic status. Thus, the collection of
      all metabolites present in a biological system at a certain time point (the so
      called metabolome) defines its physiological, developmental and pathological
      state and determines its fate during changing and stressful conditions. The
      budding yeast Saccharomyces cerevisiae is a unicellular organism that allows to
      easily modify and monitor conditions affecting the cell's metabolome, for
      instance through a simple change of the nutrition source. Such changes can be
      used to mimic and study (patho)physiological scenarios, including caloric
      restriction and longevity, the Warburg effect in cancer cells or changes in
      mitochondrial mass affecting cell death. In addition, disruption of single genes
      or generation of respiratory deficiency (via abrogation of mitochondrial DNA)
      assists in revealing connections between metabolism and apoptosis. In this
      minireview, we discuss recent studies using the potential of the yeast model to
      provide new insights into the processes of stress defense, cell death and
      longevity.

PMID- 22480869
TI  - Binary and ternary complexes based on polycaprolactone-graft-poly (N, N
      dimethylaminoethyl methacrylate) for targeted siRNA delivery.
AB  - Small interfering RNA (siRNA) is a powerful gene silencing tool and has promising
      prospects in basic research and the development of therapeutic reagents. However,
      the lack of an effective and safe tool for siRNA delivery hampers its
      application. Here, we introduced binary and ternary complexes that effectively
      mediated siRNA-targeted gene silencing. Both complexes showed excellent siRNA
      loading even at the low N/P/C ratio of 3:1:0. FACS and confocal microscopy
      demonstrated that nearly all cells robustly internalized siRNAs into the
      cytoplasm, where RNA interference (RNAi) occurred. Luciferase assay and Western
      blot verified that silencing efficacy reached >80%, and introducing folate onto
      the ternary complexes further enhanced silencing efficacy by about 10% over those
      without folate at the same N/P/C ratio. In addition, the coating of PGA-g-mPEG
      decreased the zeta potential almost to electroneutrality, and the MTT assay
      showed decreased cytotoxicity. In vivo distribution measurement and histochemical
      analysis executed in C57BL/6 and Hela tumor-bearing BALB/c nude mice showed that
      complexes accumulated in the liver, lungs, pancreas and tumors and were released
      slowly for a long time after intravenous injection. Furthermore, ternary
      complexes showed higher siRNA fluorescence intensity than binary complexes at the
      same N/P ratio in tumor tissues, those with folate delivered more siRNAs to
      tumors than those without folate, and more folate induced more siRNA transport to
      tumors. In addition, in vivo functional study showed that both binary and ternary
      complexes mediated down-regulation of ApoB in liver efficiently and consequently
      blocked the secretion of fatty acids into the blood, resulted in lipid
      accumulation in liver, liver steatosis and hepatic dysfunction. In conclusion,
      these complexes provided a powerful means of administration for siRNA-mediated
      treatment of liver-related diseases and various cancers, especial for pancreatic
      and cervical cancer.

PMID- 22480870
TI  - Tuberculosis: from molecular pathogenesis to effective drug carrier design.
AB  - In the past two decades, tuberculosis has gone from being a forgotten disease to
      a modern and recrudescent pathology. Tuberculosis is a curable infection and most
      of the negative therapeutic outcomes are related to poor patient compliance,
      which could be solved by new drug delivery approaches. By using such approaches
      the technological drawbacks of the currently used therapeutic agents could be
      addressed. In addition, optimum effectiveness of the drug by targeting the
      infection reservoirs could be achieved. In this article we compile the general
      physiological aspects of the infection along with new research updates especially
      on novel carriers used in the prevention of tuberculosis which might enhance
      therapeutic efficacy and patient compliance.

PMID- 22480871
TI  - Fluorine local environment: from screening to drug design.
AB  - Fluorine is widely used in the lead optimization phase of drug discovery
      projects. More recently, fluorine NMR-based spectroscopy has emerged as a
      versatile, reliable and efficient tool for performing binding and biochemical
      assays. Different libraries of fluorinated compounds, designed by maximizing the
      chemical space around the fluorine atom, are screened for identifying binding
      fragments and for detecting putative fluorophilic hot spots on the desired
      macromolecular target. A statistical analysis of the fluorine NMR chemical shift,
      which is a marker of the fluorine local environment, and of the X-ray structures
      of fluorinated molecules has resulted in the development of the 'rule of
      shielding'. This method could become a useful tool for lead optimization and for
      designing novel chemical scaffolds that recognize distinct protein structural
      motifs.

PMID- 22480872
TI  - 'Dying from' to 'living with': framing institutions and the coping processes of
      African American women living with HIV/AIDS.
AB  - How do HIV-positive individuals transition from believing and behaving as though
      they have a 'death sentence' to interpreting and coping with HIV as a chronic but
      manageable illness? Using interview data collected from 30 HIV-positive African
      American women beginning in 2005, we reveal how and why interactions with non
      profit and government institutions help to explain variation between those who
      thrive and those who do not following an HIV diagnosis. We argue that 'framing
      institutions' shape the form and tenor of coping trajectories by offering initial
      information about one's HIV status, a conceptual framework for understanding what
      it means to have HIV, language to talk about one's condition, and resources to
      begin restructuring one's life in the wake of a diagnosis. Ultimately, we
      highlight how a diverse array of non-profit and government institutions not only
      play a critical part in helping women cope with HIV but also renegotiate their
      self-conceptions as black women in the wake of receiving another stigmatizing
      social marker. In short, organizational ties shape women's movement from beliefs
      and behaviors that suggest that they are 'dying from' this disease to attitudes
      and actions consistent with the notion that they can 'live with' HIV.

PMID- 22480873
TI  - Alienating evidence based medicine vs. innovative medical device marketing: a
      report on the evidence debate at a Wounds conference.
AB  - Wound care management is one of the largest segments of the UK medical technology
      sector with a turnover exceeding L1bn in 2009 (BIS, 2010). Using data derived
      from participant observation, this article examines the antagonistic relationship
      expressed by wound care clinicians towards evidence based medicine in the context
      of the 2010 United Kingdom (UK) Wounds UK conference/trade show, where evidence
      based medicine is positioned in opposition to clinical knowledge, as an obstacle
      to innovation and as a remover of solutions rather than a provider of them. The
      article is written in the context of the trend towards increasing marketization
      and privatization in the UK National Health Service (NHS).

PMID- 22480874
TI  - Post-transcriptional CD59 gene silencing by siRNAs induces enhanced human T
      lymphocyte response to tumor cell lysate-loaded DCs.
AB  - CD59 is a complement regulatory protein known to prevent the membrane attack
      complex (MAC) from assembling. To investigate the role of CD59 molecules in human
      T cell activation in response to exogenous antigens, gene silencing via small
      interfering RNAs (siRNAs) was carried out. Subsequent T cell activation in
      response to both autologous dendritic cells (DCs) loaded with tumor lysate and
      beads coated with anti-CD3, anti-CD28 and anti-CD59 antibodies was investigated.
      The findings demonstrated that decreased CD59 expression on T cells significantly
      enhanced activation and proliferation of CD4(+) T cells and CD8(+) T cells while
      the expansion of CD4(+) CD25(+) regulatory T cells (Tregs) was not affected, and
      CD59 mediated inhibition of T cell activation requires the binding of CD59 with
      its ligand on antigen-presenting cells (APCs). The data support that CD59 down
      regulates antigen-specific activation of human T lymphocytes in a ligand
      dependent manner.

PMID- 22480875
TI  - Down regulation of CD24 and HER-2/neu in breast carcinoma cells by activated
      human dendritic cell. Role of STAT3.
AB  - Human dendritic cells (DCs) stimulated with cytokines and LPS down regulate the
      expression of proto-oncogene HER-2/neu and GPI linked protein CD24 in breast
      cancer cell lines. We demonstrated that naive DC from human peripheral blood,
      when stimulated with IFN-gamma, IL-15 or LPS reduces the expression of HER-2/neu
      and CD24, via activation of TNF-alpha. Pretreatment of tumor cells with STAT3
      specific inhibitors or knocking down of STAT3 by SiRNA makes the tumor cell more
      susceptible to apoptosis and DC mediated inhibition of both CD24 and HER-2/neu.
      Thus DC could acts as an inhibitory regulator in suppressing oncogene and
      prevention of metastasis.

PMID- 22480876
TI  - Analysis of an implantable venous anastomotic flow coupler: experience in head
      and neck free flap reconstruction.
AB  - Monitoring microvascular free flaps can present a difficult challenge. This is
      especially true in cases of buried or intra-oral free flaps. The authors
      conducted a retrospective review of 19 consecutive free flaps for head and neck
      reconstruction using a novel monitoring device, which combines a venous
      anastomotic coupler and an implantable microdoppler (Synovis Micro Companies
      Alliance Inc., Birmingham, AL, USA). 20 venous anastomoses were performed and
      monitored with the venous flow coupler device. Monitoring ranged from intra
      operatively to postoperative day 7 (mean 4.2 days). Accurate flow signal
      interpretation was correct in 18 of 20 anastomoses (90%) but only 14 of the 20
      coupled anastomoses (70%) were monitored for the complete period of time as
      desired by the surgeons. All 19 flaps survived. The venous anastomotic flow
      coupler appears to be a reliable adjunct to free flap monitoring and may help to
      improve it, with early detection of flap compromise and salvage.

PMID- 22480877
TI  - Life-threatening haemorrhage after 750 Le Fort I osteotomies and 376 SARPE
      procedures.
AB  - This study assessed the incidence, presenting symptoms, diagnosis, and management
      of patients with life-threatening postoperative haemorrhage after total Le Fort I
      osteotomy and surgically assisted rapid palatal expansion (SARPE). The medical
      records of 750 consecutive Le Fort I osteotomies and 376 consecutive SARPEs, both
      of which involved pterygomaxillary separation with a curved osteotome and a
      mallet, were analysed prospectively. Two cases of life-threatening haemorrhage
      were observed in the Le Fort I osteotomy group, both initiated on postoperative
      day 7. Anterior and posterior nasal packing were successful in one patient; the
      other required two embolizations for bleeding control (incidence of life
      threatening postoperative haemorrhage: 2/750; confidence interval: 0.03-0.96%).
      In the SARPE group, one brisk epistaxis on the first postoperative day was
      controlled with anterior and posterior nasal packing under general anaesthesia.
      This haemorrhage was not considered life threatening (incidence of life
      threatening postoperative haemorrhage: 0/376; confidence interval: 0-0.98%). In
      no case could the source of bleeding be established during re-explorative surgery
      or during diagnostic arteriography. The authors conclude that life-threatening
      haemorrhage is an exceptional finding after Le Fort I osteotomy; the observed
      incidence was 2/750, and life-threatening haemorrhage was not observed after
      SARPE in this series, despite the use of identical pterygomaxillary separation.

PMID- 22480878
TI  - A single microcircuit with multiple functions: state dependent information
      processing in the hippocampus.
AB  - Many neural circuits process information in multiple distinct modes. For example,
      the hippocampus is involved in memory encoding, retrieval, and consolidation
      processes. These different mnemonic computations require processing of differing
      balances of current sensory input and previously stored associations. Here we
      explore patterns of activity in hippocampal output area CA1 associated with
      different information processing states. We discuss the evidence linking these
      patterns to specific inputs to CA1 and describe behavioral factors that are
      related to the balance of synaptic drive. We suggest that understanding the
      factors that influence information flow in the hippocampal circuit could provide
      important new insights into how neural circuits are reconfigured on the fly to
      perform different functions at different times.

PMID- 22480879
TI  - Short-term adaptation of accommodation, accommodative vergence and disparity
      vergence facility.
AB  - Previous studies have found that subjects can increase the velocity of
      accommodation using visual exercises such as pencil push ups, flippers, Brock
      strings and the like and myriad papers have shown improvement in accommodation
      facility (speed) and sufficiency (amplitude) using subjective tests following
      vision training but few have objectively measured accommodation before and after
      training in either normal subjects or in patients diagnosed with accommodative
      infacility (abnormally slow dynamics). Accommodation is driven either directly by
      blur or indirectly by way of neural crosslinks from the vergence system. Until
      now, no study has objectively measured both accommodation and accommodative
      vergence before and after vision training and the role vergence might play in
      modifying the speed of accommodation. In the present study, accommodation and
      accommodative-vergence were measured with a Purkinje Eye Tracker/optometer before
      and after normal subjects trained in a flipper-like task in which the stimulus
      stepped between 0 and 2.5 diopters and back for over 200 cycles. Most subjects
      increased their speed of accommodation as well as their speed of accommodative
      vergence. Accommodative vergence led the accommodation response by approximately
      77 ms before training and 100 ms after training and the vergence lead was most
      prominent in subjects with high accommodation and vergence velocities and the
      vergence leads tended to increase in conjunction with increases in accommodation
      velocity. We surmise that volitional vergence may help increase accommodation
      velocity by way of vergence-accommodation cross links.

PMID- 22480880
TI  - The influence of visual motion on interceptive actions and perception.
AB  - Visual information is an essential guide when interacting with moving objects,
      yet it can also be deceiving. For instance, motion can induce illusory position
      shifts, such that a moving ball can seem to have bounced past its true point of
      contact with the ground. Some evidence suggests illusory motion-induced position
      shifts bias pointing tasks to a greater extent than they do perceptual judgments.
      This, however, appears at odds with other findings and with our success when
      intercepting moving objects. Here we examined the accuracy of interceptive
      movements and of perceptual judgments in relation to simulated bounces.
      Participants were asked to intercept a moving disc at its bounce location by
      positioning a virtual paddle, and then to report where the disc had landed.
      Results showed that interceptive actions were accurate whereas perceptual
      judgments were inaccurate, biased in the direction of motion. Successful
      interceptions necessitated accurate information concerning both the location and
      timing of the bounce, so motor planning evidently had privileged access to an
      accurate forward model of bounce timing and location. This would explain why
      people can be accurate when intercepting a moving object, but lack insight into
      the accurate information that had guided their actions when asked to make a
      perceptual judgment.

PMID- 22480881
TI  - Defining Wilson disease phenotypes: from the patient to the bench and back again.

PMID- 22480882
TI  - Association between contamination of public squares and seropositivity for
      Toxocara spp. in children.
AB  - A concomitant study was carried out, of the association of positive serology for
      Toxocara spp. in 90 children who played in public squares used for leisure, with
      the frequency with which each child used these areas, and the presence of eggs of
      Toxocara spp. in the sand or grass in these locations. The sand and grass of
      their peridomiciles and school playgrounds, as well as the feces of their dogs
      were also analyzed for Toxocara. Serum samples were tested for IgG antibodies to
      Toxocara canis excreted-secreted larval antigens by ELISA, and blood samples for
      eosinophilia. The water-sedimentation technique was used to evaluate the presence
      of parasite eggs in the sand and grass turfs, and in feces of the dogs that also
      frequented these locations. 16/90 (17.8%) of the children were seropositive for
      Toxocara spp. There was a positive association between seropositivity in children
      who played in the public squares six or seven times a week, with a parasite load
      above 1.1 eggs/g of sand, as well as with contamination of the peridomicile, even
      at less than 1.0 egg/g of sand. Eosinophilia, the habit of geophagy, age from one
      to four years, and the presence of parasitized pet dogs were also positively
      correlated with seropositivity in the children. Eggs were found in 15/15 (100%)
      of the public squares, 17/90 (18.9%) of the peridomiciles, 3/13 (23.1%) of the
      schools, and 12/41 (29.3%) of the dogs living in the peridomiciles investigated.

PMID- 22480883
TI  - Effect of oil-based formulations of acaripathogenic fungi to control
      Rhipicephalus microplus ticks under laboratory conditions.
AB  - The formulations of acaripathogenic fungi to control ticks have been widely
      studied. The present study evaluated the efficacy of oil-based formulations of
      Metarhizium anisopliae sensu lato (s.l.), isolate Ma 959, and Beauveria bassiana,
      isolate Bb 986, on different Rhipicephalus microplus stages, comparing the
      efficacy between aqueous suspensions and 10, 15 and 20% mineral oil formulations.
      Twelve groups were formed: one aqueous control group; three mineral oil control
      groups, at 10, 15 or 20%; two aqueous fungal suspensions of M. anisopliae s.l. or
      B. bassiana; and three formulations of M. anisopliae (s.l.) or B. bassiana
      containing 10, 15, and 20% mineral oil. To prepare aqueous suspensions and oily
      formulations, fungal isolates were cultivated on rice grains in polypropylene
      bags. The conidial suspensions and formulations had a concentration of
      10(8)conidia/mL. Bioassays were repeated twice. After treatment, the following
      biological parameters of engorged females were evaluated: hatching percentage,
      egg production index, nutritional index, and percentage of tick control. The
      following parameters were evaluated in the bioassays with eggs: period of
      incubation, period of hatch, and hatching percentage. Mortality was evaluated in
      bioassays with larvae. M. anisopliae s.l. and B. bassiana oil-based formulations
      were more effective than aqueous suspensions against R. microplus eggs, larvae
      and engorged females, however, there was no significant difference between the
      three oil concentrations used. M. anisopliae s.l. and B. bassiana formulated in
      mineral oil reached 93.69% and 21.67% efficacy, respectively, while M. anisopliae
      s.l. and B. bassiana aqueous suspensions attained 18.70% and 1.72% efficacy,
      respectively. M. anisopliae s.l. oil-based formulations caused significant
      effects in all biological parameters of engorged females while B. bassiana oil
      based formulations modified significantly the nutritional index only. Eggs
      treated with M. anisopliae s.l. and B. bassiana oil-based formulations showed
      hatching rates that decreased 102.5 and 3.65 times, respectively. In the bioassay
      with larvae, M. anisopliae s.l. oil-based formulations caused nearly 100%
      mortality five days after treatment, while larva treated with B. bassiana oil
      based formulations reached 100% mortality at day 20 after treatment. Larva from
      oil-based control groups showed mortality at day 15 after treatment, which
      indicated a possible toxic effect of the oil for this R. microplus stage. The
      results showed that the fungal mineral oil formulations tested were more
      effective than the aqueous suspension. Oil-based formulations at 10, 15 and 20%
      enhanced the activity of M. anisopliae s.l. Ma 959, and B. bassiana Bb 986,
      isolates against R. microplus eggs, larvae, and engorged females tick. Mineral
      oil was effective as an adjuvant in formulations of M. anisopliae s.l., Ma 959,
      and B. bassiana, Bb 986, for the control of R. microplus under laboratory
      conditions.

PMID- 22480884
TI  - Background and current status of postmortem imaging in Japan: short history of
      "Autopsy imaging (Ai)".
AB  - There is a low autopsy rate and wide distribution of computed tomography (CT) and
      magnetic resonance imaging (MRI) scanners in Japan. Therefore, many Japanese
      hospitals, including 36% of the hospitals with in-patient facilities and 89% of
      large hospitals with ER facilities conduct postmortem imaging (PMI), use clinical
      scanners to screen for causes in unusual deaths as an alternative to an autopsy
      or to determine whether an autopsy is needed. The Japanese PMI examination
      procedure is generally referred to as "autopsy imaging" (Ai) and the term "Ai" is
      now commonly used by the Japanese government. Currently, 26 of 47 Japanese
      prefectures have at least one Ai Center with scanners that are dedicated for PMI.
      Here, we briefly review the history of Japanese PMI (Ai) from 1985 to the
      present.

PMID- 22480885
TI  - Hemi-aortic arch debranching for hybrid aortic arch repair by sequential
      transposition of the left common carotid and subclavian arteries.
AB  - OBJECTIVE: The aim of this study was to assess the short-term and midterm results
      after hemi-aortic arch debranching for hybrid aortic arch repair by sequential
      transposition of the left common carotid artery and of the left subclavian
      artery. METHODS: From November 1998 to August 2011, 11 patients underwent a
      hybrid technique with supra-aortic debranching (by sequential transposition of
      the left common carotid artery and of the left subclavian) and simultaneous
      endovascular stent grafting for zone 1 lesions. There were 8 men and 3 women
      (mean age, 62.9 +/- 20.9 years; range, 15-89 years). Aortic arch lesions treated
      included 4 complicated aortic dissections, 3 degenerative aneurysms, 2
      postcoarctectomy aortic pseudoaneurysms, 1 mycotic aneurysm, and 1 traumatic
      transection of the arch. Four (36%) operations were performed in an emergency
      setting. RESULTS: Endovascular exclusion success was achieved in 90.9% of the
      patients (type I endoleak: 1/11). One iliac artery rupture occurred
      intraoperatively. The 30-day mortality rate was 0%. Overall actuarial survival
      was 82% and 71.8% at 1 and 2 years. Mean follow-up is 31 +/- 25 months (range, 3
      72 months). No instance of permanent cerebral or spinal cord ischemia was
      observed. Two type II endoleaks are currently observed. There was no device
      migration. CONCLUSIONS: Hybrid aortic arch repair by sequential transposition of
      the left common carotid artery and of the left subclavian artery for zone 1
      lesions provides an attractive alternative for treating hemi-aortic arch lesions
      in high-risk patients with minimal atherosclerotic disease in the aorta and great
      vessels with acceptable primary results and encouraging midterm efficacy to
      prevent rupture. This hybrid strategy avoiding prosthetic bypass offers several
      advantages over conventional repair, including the potential to treat patients
      who are not candidates for open repair and single-stage treatment of some
      pathologic conditions previously requiring 2-stage repair.

PMID- 22480886
TI  - Effect on blood pressure of a dietary supplement containing traditional medicinal
      plants of Cote d'Ivoire.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A medicinal composition containing salt (sodium
      chloride) is given as a traditional dietary supplement to hypertensive patients
      (TDSHP) in Cote d'Ivoire. It consists of whole plant of Bidens pilosa
      (Asteraceae) and fresh leaves of Moringa oleifera (Moringaceae). AIM OF THE
      STUDY: The aim of this study was to establish the scientific basis for the use of
      this traditional recipe rich in sodium chloride in hypertension settings.
      MATERIALS AND METHODS: We used a total aqueous extract of this traditional
      dietary supplement containing medicinal plants (Bidens pilosa, Moringa oleifera)
      and salt (sodium chloride). Experiment was carried out to evaluate its effect on
      arterial blood pressure of rabbits. The experimental device used for recording
      blood pressure in rabbits is based on the principle of Ludwig mercury manometer.
      RESULTS: TDSHP between 5*10(-8) and 5*10(-2) mg/kg caused a dose-dependent
      hypotension. TDSHP elicited drops in blood pressure ranging between 7.14+/-4 and
      100+/-7.5%, compared to normal blood pressure of rabbits. Fifty percent effective
      dose of TDSHP was 3.95*10(-4) mg/kg. Similarly as the hypotension induced by
      acetylcholine, the one caused by TDSHP at dose of 3.95*10(-4) mg/kg in rabbit was
      progressively inhibited by atropine, dosed between 5*10(-4) to 5*10(-2) mg/kg.
      The percentage drop of recorded blood pressure ranged from 50.3+/-1.87 to 3.71+/
      1.09% compared to the normal value of blood pressure. In the presence of
      atropine, TDSHP effect was partially inhibited. The same increasing doses of
      TDSHP reduced significantly the increase of blood pressure induced by adrenaline
      dosed at 4.76*10(-4) mg/kg from 89.3+/-2.19 to 1.19+/-0.59%. CONCLUSION: The
      consumption of this traditional dietary supplement is justified in hypertensive
      patients according to its composition and its ability to reduce blood pressure
      has been demonstrated experimentally. TDSHP should not be considered as an
      antihypertensive drug, it remains to us a salt substitute to be taken with
      moderation with strict adherence to the traditional dose.

PMID- 22480887
TI  - Neighbourhood food environments and obesity in southeast Louisiana.
AB  - Supermarkets might influence food choices, and more distal outcomes like obesity,
      by increasing the availability of healthy foods. However, recent evidence about
      their effects is ambiguous, perhaps because supermarkets also increase the
      availability of unhealthy options. We develop an alternative measure of food
      environment quality that characterizes urban neighborhoods by the relative
      amounts of healthy (e.g. fruits and vegetables) to unhealthy foods (e.g. energy
      dense snacks). Using data from 307 food stores and 1243 telephone interviews with
      residents in urban southeastern Louisiana, we estimate a multilevel multinomial
      logistic model for overweight status. We find that higher quality food
      environments - but not food store types - decrease the risk of obesity (RR 0.474,
      95% CI 0.269-0.835) and overweight (RR 0.532, 95% CI 0.312-0.907). The findings
      suggest a need to move beyond a sole consideration of food store types to a more
      nuanced view of the food environment when planning for change.

PMID- 22480888
TI  - [Medical education during the practicum year].

PMID- 22480889
TI  - Final year medical education in Germany.
AB  - Medical education in Germany has undergone significant changes. The current
      article attempts to give an overview of final year medical education in Germany
      and implications for further developments. Challenges in final year medical
      education mainly arise from the lack of clearly defined learning objectives, the
      provision of structure, independent patient management and professional guidance
      and supervision. The abolition of the one-and-a-half-year period of pre
      registration medical training in 2004 and the changes in the structure of state
      examinations in line with the amendment of medical licensing regulations in 2002,
      meant pressure on the efficiency of final year medical education on the one hand,
      and additional burden on final year students on the other. In this article, a
      broad variety of innovative models that have been implemented at different
      medical faculties, and which address final year students' needs, will be
      reported. Further challenges, such as the integration of general medicine
      rotations, the abolishment of the second state examination in its present form,
      and the integration of final year students' individual career plans will be
      discussed.

PMID- 22480890
TI  - The clinical electives year in undergraduate medical training in Switzerland: an
      overview.
AB  - In Switzerland undergraduate medical training has undergone several reforms over
      the last decade which also affected the integration, the structure as well as the
      learning content of the so-called "Wahlstudienjahr" (clinical electives year).
      The first section of this paper gives a short overview of the current status of
      the clinical electives year in Switzerland. In the second section some
      descriptive data concerning the Faculty of Medicine in Zurich are summarized to
      exemplify current and future aspects of the quality development in the clinical
      electives year in Switzerland.

PMID- 22480891
TI  - Easing the transition: the final year of medical education at Maastricht
      University.
AB  - This manuscript describes the final year of medical education at Maastricht
      University as it has been operating since 2006. At the time external drivers for
      the development of a new structure of the final year were: the desire to prepare
      medical students for lifelong learning, the CanMEDs that were increasingly
      acknowledged to state the final attainment level of medical education and an
      increasing recognition of the importance of learning by participating actively
      and by taking more responsibility. Internal drivers were students' evaluations
      and our wish to improve instructional design and quality control. The main aim of
      this new final year is to better prepare students for the transition from the
      medical master programme to one of the postgraduate training programmes to become
      a medical specialist. The final year of the medical master programme consists of
      two 18-weeks participation electives, one in health care and one in research.
      Students have a higher level of autonomy and responsibility during this final
      year compared to the preceding medical clerkships to enhance the transition.
      Portfolios are the key element in examination of SCIP and HELP. Student
      evaluations of the final year show high scores on coaching and instructiveness.
      Despite some differences between departments overall scores are very high.
      Suggestions to improve include the availability of work places and time for
      education and coaching.

PMID- 22480892
TI  - [Report of experiences: on the threshold of becoming a physician].

PMID- 22480893
TI  - ["Working like a doctor": medical students' expectations of their final year
      elective in Family Medicine].
AB  - BACKGROUND: Successful curricular development requires that consideration be
      given to the opinions of faculty members, teachers and students. The aim of the
      present study was to explore students' expectations of the final year Family
      Medicine elective. METHODS: Three focus group discussions took place with a total
      of 15 participants who were either in their fifth year (n=11) or had already
      passed Family Medicine in their final year (third focus group). The discussions
      were transcribed verbatim and analysed independently by two of the authors using
      qualitative content analysis. Final codes were developed and clustered under
      category names. RESULTS: As students found that Medical School was too
      theoretical, they aimed at learning through practice in order to be able to make
      decisions and act independently. Their ideal teacher would respect them as
      colleagues. Typical Family Medicine skills were mentioned less often by the "pre
      " in contrast to the "post-" practical year students than the learning of
      technical aspects (ECG, ultrasound). The students discussed three different
      models of instruction and learning (student and patient alone, student or doctor
      observes consultation). CONCLUSIONS: Considering that the final year elective in
      Family Medicine will take place away from Medical School different teaching
      models should be evaluated for their effectiveness as well as their learner
      centeredness.

PMID- 22480894
TI  - [Evaluation of a structured, longitudinal training program for the preparation
      for the second state exam (M2) - a quantitative analysis].
AB  - INTRODUCTION: The implementation of the amendment to the German medical licensing
      regulations ("Approbationsordnung") in 2002 led to a reduction in the number of
      state examinations from four to two exams, with the date of the second state exam
      being shifted to the end of the final clinical year. Students now face a double
      burden: on the one hand, they need to get ready for their future job, and on the
      other hand, they need to prepare for the state exam. This is why the Medical
      Faculty of Heidelberg introduced a preparation programme for the second state
      exam. The focus of this study was to evaluate the acceptance of the different
      modules of this programme and to compare the results against each other. METHODS:
      39 students (15 male / 24 female; mean age 26.6 +/- 1.9 years) took part in the
      exam preparation programme at the Medical University Hospital Heidelberg. Five
      different modules were implemented: an informational meeting, a key-feature
      written exam, case-based multiple-choice exams, a simulated practical examination
      and a simulated oral examination. Acceptance was measured using a six-point
      Likert scale (1=very good, 6=unsatisfactory and 1=I completely agree, 6=I
      completely disagree, respectively) RESULTS: The exam preparation programme as a
      whole was rated good: overall rating key-feature written exam 3.33 +/- 1.17; case
      based multiple-choice exams 2.61 +/- 1.61; simulated practical exam 1.61 +/-
      0.54; simulated oral exam 1.55 +/- 0.50. A comparison of the different modules
      demonstrated significantly better ratings for the practical and oral examinations
      than the case-based multiple-choice exams (p<0.001). DISCUSSION: The presented
      exam preparation programme is well accepted and facilitates the preparation for
      the second state exam, particularly with regard to the oral-practical
      examination.

PMID- 22480895
TI  - [Burdened into the job -- final-year students' empathy and burnout].
AB  - BACKGROUND: Empathy is a central element in daily patient care. The burnout
      syndrome seems to be a potential factor influencing physicians' empathic behavior
      negatively. In Germany up to 20 % of practicing physicians experience burnout. So
      far, there have been no studies measuring empathy and the degree of burnout among
      final-year medical students in Germany. The aim of the current study was to
      investigate final-year students' self-reported empathy, burnout and the
      association of job satisfaction and occupational self-efficacy with regard to
      potential gender differences. METHODS: 127 medical students at the end of their
      final year (82 f, 45 m; 26.8 years of age) were surveyed using the Jefferson
      Scale of Physician Empathy (JSPE), the Maslach Burnout Inventory (MBI) and items
      addressing job satisfaction and occupational self-efficacy. RESULTS: The mean
      JSPE score of all final-year students was 113.25 +/- 10.21 (20=lowest possible
      empathy score, 140=highest possible empathy score). Based on the three dimensions
      of burnout, the students fell in the moderate burnout category in all subscales
      of the MBI. There was an association between a lower empathy score and a higher
      burnout score. Also, the MBI correlated negatively with final-year students' job
      satisfaction and occupational self-efficacy. CONCLUSION: Despite high self-rated
      empathy scores, the experience of burnout symptoms in medical students may begin
      as early as their final year of studies, where higher levels of burnout are
      associated with lower self-rated empathy scores. The number of final-year medical
      students affected by clinically significant burnout (up to 20 %) was just as high
      as among practicing physicians. Female students were found to be particularly
      affected. Given the rising numbers of female graduates, this shows that urgent
      action is required.

PMID- 22480896
TI  - [What is the purpose of the German Aptitude Test for Medical Studies (TMS)?].
AB  - The German Aptitude Test for Medical Studies (TMS) was implemented in 2007.
      12,194 persons registered for this test in 2011, which represents a 91% increase
      over 2007. The male/female ratio remained constant at 38:62. Its reliability
      among applicants to Heidelberg Medical Faculty was confirmed by Cronbach's alpha
      (>= 0.75) and inter-item correlation (>= 0.25, p < 10(-7)). The TMS contains nine
      items; using factor analysis these were allocated to the two components verbal
      mathematical and spatial-figural ability. The verbal-mathematical items
      moderately correlate with the German Baccalaureate GPA (r = 0.33), while the
      spatial-figural items do not correlate (r = 0.07). Thus, the TMS is an admission
      instrument that appraise different cognitive abilities than the GPA. For the
      admission of students to our faculty their TMS scores are weighted at 39%, which
      has resulted in a diversification of our student cohorts.

PMID- 22480897
TI  - [Medications: increasing treatment safety for patients and informing physicians].

PMID- 22480898
TI  - Decreased sensitivity to facial emotions in adolescents with Borderline
      Personality Disorder.
AB  - Whereas severe relationship dysfunction in BPD is well described in adolescence,
      little is known about the way these patients process facial expressions of
      emotion. Because few data are available regarding this issue, the present study
      compared the sensitivity to morphed facial emotional expressions of 22 BPD female
      adolescents versus 22 matched controls. Participants had to identify as rapidly
      as possible the various emotions displayed progressively and continuously on
      faces. Results indicate that adolescents with BPD are less sensitive to facial
      expressions of anger and happiness, i.e. they require more intense facial
      expressions than control participants to correctly identify these two emotions.
      However, they did not exhibit any deficit in recognizing fully expressed
      emotions. These results suggest that sensitivity to facial emotions is impaired
      in adolescents with BPD. Theoretical and clinical implications are discussed.

PMID- 22480899
TI  - Modification, calibration and verification of the IWA River Water Quality Model
      to simulate a pilot-scale high rate algal pond.
AB  - We implemented the IWA River Water Quality Model No. 1 (Reichert et al., 2001.
      River Water Quality Model No. 1, IWA Scientific & Technical Report No. 12) to
      simulate water-quality characteristics in two pilot-scale High Rate Algal Ponds.
      Simulation results were compared with two years' of data from the ponds. The
      first year's data from one pond were used for model calibration; the remaining
      data were used for validation. As originally formulated and parameterized, the
      model consistently yielded summer-time algal biomass concentrations which were
      too low - with consequent failures in its reproduction of dissolved oxygen, pH
      and nutrient dynamics. We experimented with various structural/parametric changes
      to improve the model's performance. The most effective strategy was to greatly
      increase the respiratory losses suffered by the heterotrophic osmotrophs (thereby
      giving the algae access to a larger fraction of the incoming dissolved organic
      carbon and nitrogen). This suggests that CO(2)-bubbling alone cannot entirely
      preclude resource-limitation of algal production. We doubt that our
      parameterization of heterotrophic osmotrophs is correct and infer that the algae
      derive a large fraction of their nutrition by direct osmotrophic uptake of
      dissolved organic matter. This inference is supported by the literature
      concerning the physiology of the dominant algal species in our ponds.

PMID- 22480900
TI  - Differences among major depressive disorder with and without co-occurring
      substance use disorders and substance-induced depressive disorder: results from
      the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: To investigate the association between substance use disorders (SUDs)
      and the clinical presentation, risk factors, and correlates of major depressive
      disorder (MDD) by examining differences among 3 groups: (1) individuals with
      lifetime MDD and no comorbid SUD (MDD-NSUD); (2) individuals with comorbid MDD
      and SUD (MDD-SUD); and (3) individuals with substance-induced depressive disorder
      (SIDD). METHOD: Data were derived from the 2001-2002 National Epidemiologic
      Survey on Alcohol and Related Conditions (N = 43,093). Diagnoses were made using
      the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV
      Version. RESULTS: The lifetime prevalence of MDD-NSUD was 7.41%, whereas those of
      MDD-SUD and SIDD were 5.82% and 0.26%, respectively. Overall, risk factors for
      MDD were more common among individuals with MDD-SUD and SIDD than among those
      with MDD-NSUD. Individuals with MDD-SUD and SIDD had similar rates of comorbidity
      with any psychiatric disorder, but both groups had higher rates than individuals
      with MDD-NSUD (odds ratio [OR] = 2.3; 95% CI, 1.9-2.7 and OR = 2.5; 95% CI, 1.4
      4.4, respectively). Individuals with SIDD were significantly less likely to
      receive medication than those with MDD-SUD or MDD-NSUD (OR = 0.5; 95% CI, 0.3-0.9
      for both groups). CONCLUSIONS: MDD-SUD is associated with high overall
      vulnerability to additional psychopathology, a higher number of and more severe
      depressive episodes, and higher rates of suicide attempts in comparison to
      individuals with MDD-NSUD. SIDD has low prevalence in the general population but
      is associated with increased clinical severity and low rates of medication
      treatment. Similar patterns of comorbidity and risk factors in individuals with
      SIDD and those with MDD-SUD suggest that the 2 conditions may share underlying
      etiologic factors.

PMID- 22480902
TI  - Closure of apical access site after transapical, transcatheter paravalvular leak
      closure.
AB  - The safety of percutaneous transapical mitral paravalvular leak (PVL) closure
      could potentially be enhanced by device closure of the ventricular access site.
      Percutaneous transapical PVL closure was performed. The 9F delivery sheath was
      pulled back, and a 6-mm Amplatzer muscular ventricular septal defect occluder was
      deployed at the apical puncture site. Immediate hemostasis was achieved. Total
      hospitalization was 9 days. New York Heart Association functional class was
      improved, hemoglobin and haptoglobin rose, while lactate dehydrogenase fell.
      Follow-up fluoroscopy and transthoracic echocardiography revealed a good
      functional result. Closure of the apical access site by means of an Amplatzer
      muscular ventricular septal defect occluder is feasible.

PMID- 22480901
TI  - Ambulatory surveillance of patients referred for cardiac rehabilitation following
      cardiac hospitalization: a feasibility study.
AB  - BACKGROUND: Our purpose was to examine the feasibility of implementing an
      ambulatory surveillance system for monitoring patients referred to cardiac
      rehabilitation following cardiac hospitalizations. METHODS: This study consists
      of 1208 consecutive referrals to cardiac rehabilitation between October 2007 and
      April 2008. Patient attendance at cardiac rehabilitation, waiting times for
      cardiac rehabilitation, and adverse events while waiting for cardiac
      rehabilitation were tracked by telephone surveillance by a nurse. RESULTS: Among
      the 1208 consecutive patients referred, only 44.7% attended cardiac
      rehabilitation; 36.4% of referred patients were known not to have attended any
      cardiac rehabilitation, while an additional 18.9% of referred patients were lost
      to follow-up. Among the 456 referred patients who attended the cardiac
      rehabilitation program, 19 (4.2%) experienced an adverse event while in the queue
      (13 of which were for cardiovascular hospitalizations with no deaths), with mean
      waiting times of 20 days and 24 days among those without and with adverse events,
      respectively. Among the 440 referred patients who were known not to have attended
      any cardiac rehabilitation program, 114 (25.9%) had adverse clinical events while
      in the queue; 46 of these events required cardiac hospitalization and 8 patients
      died. CONCLUSIONS: Ambulatory surveillance for cardiac rehabilitation referrals
      is feasible. The high adverse event rates in the queue, particularly among
      patients who are referred but who do not attend cardiac rehabilitation programs,
      underscores the importance of ambulatory referral surveillance systems for
      cardiac rehabilitation following cardiac hospitalizations.

PMID- 22480903
TI  - Emery-Dreifuss humeroperoneal muscular dystrophy: cardiac manifestations.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder affecting
      skeletal and cardiac muscles and characterized by muscular atrophy, contractures,
      and cardiomyopathy with conduction defects. It can be X-linked or autosomal. Not
      all patients with EDMD develop heart involvement, but heart disease associated
      with EDMD can be unpredictable and may be life threatening. In rare cases heart
      problems may be the first symptom of EDMD. Early recognition of heart involvement
      is of utmost importance as placement of a pacemaker and/or defibrillator may be
      lifesaving.

PMID- 22480904
TI  - Synchronization between embryo development and endometrium is a contributing
      factor for rescue ICSI outcome.
AB  - Recent evidence shows that the outcome of rescue intracytoplasmic sperm injection
      (ICSI) is unsatisfactory on account of a poor clinical pregnancy rate. These
      outcomes may be due to either the in-vitro ageing of cultured oocytes before ICSI
      or the asynchrony between the embryo developmental stage and the endometrial
      secretory pattern. To address the latter issue, this study performed a
      retrospective analysis of 534 fresh cycles after rescue ICSI and 64 frozen-thawed
      cycles in subsequent treatment. Rescue ICSI cycles were divided into three
      groups: group I included 469 fresh embryo-transfer (FET) cycles; group II
      included 74 FET cycles in which supernumerary good-quality embryos were also
      cryopreserved; and group III included 64 frozen-thawed transfer cycles. Group III
      was considered to have achieved better synchronization than group II. As a
      result, significantly higher clinical pregnancy (29.69%, 19/64 versus 10.81%,
      8/74) and implantation (13.33%, 22/165 versus 5.13%, 8/156) rates were achieved
      in group III compared with group II (both P<0.05). Therefore, synchronization of
      embryo development with the endometrium is considered a contributing factor for
      rescue ICSI outcome. It is recommended that embryos derived from rescue ICSI
      cycles should be cryopreserved and subsequently used in frozen-thawed cycles.
      Intracytoplasmic sperm injection (ICSI) of unfertilized 1-day-old oocytes, called
      rescue ICSI, has frequently been performed in some infertility centres, when
      fertilization failure sometimes occurs in conventional IVF cycles. Recent studies
      showed that the outcome of rescue ICSI was unsatisfactory due to poor clinical
      pregnancy rates. One reason could be asynchrony between the embryo developmental
      stage and the endometrial secretory pattern. To address this issue, we performed
      a retrospective analysis of 534 fresh cycles after rescue ICSI (from January 2006
      to January 2011) and 64 frozen-thawed transfer cycles in subsequent treatment
      (from January 2006 to May 2011) in our infertility centre. In this study, rescue
      ICSI cycles were divided into three groups. As there was no significant
      difference in women's age (31.22 +/- 3.38 versus 31.11 +/- 3.27 years) between
      groups II and III, we principally compared these two groups. Group II included 74
      fresh embryo transfer cycles, in which supernumerary good-quality embryos were
      cryopreserved, and group III included 64 frozen-thawed transfer cycles. Group III
      was considered to have better synchronization than group II. As a result,
      significantly higher clinical pregnancy (29.69% versus 10.81%) and implantation
      (13.33% versus 5.13%) rates were achieved in group III compared with group II.
      Therefore, endometrial synchronization is considered a contributing factor for
      rescue ICSI outcome and embryos derived from rescue ICSI cycles should be
      cryopreserved and subsequently used in frozen-thawed cycles.

PMID- 22480905
TI  - Unravelling the proteome of wool: towards markers of wool quality traits.
AB  - With ongoing efforts to make wool more competitive alongside other fibres,
      notably synthetics, there is a need to obtain a better understanding of the
      relationship between protein composition and characteristic wool properties to
      assist sheep breeding programmes. Before this can be achieved, the wool proteome
      needs to be mapped, by gel and non-gel techniques, and methods developed to
      reliably quantitate protein expression. Nevertheless, in setting out to achieve
      this, there are numerous challenges to be faced in the application of proteomics
      to wool, including the relative lack of wool protein sequence information in the
      publically accessible databases, the wide variety of proteins in the wool fibre,
      the high homology within the Type I and Type II keratins, the high degree of
      homology and polymorphism within individual keratin associated protein families,
      the dominance of the keratin proteins over others in wool and the peculiar
      chemistries found in keratins and their associated proteins. This review will
      discuss the various strategies that have been developed to both identify these
      proteins in the wool protein map and quantify them with the view to their
      application to the identification of markers for wool quality traits.

PMID- 22480906
TI  - Longitudinal analysis of taurine induced effects on the tear proteome of contact
      lens wearers and dry eye patients using a RP-RP-Capillary-HPLC-MALDI TOF/TOF MS
      approach.
AB  - Tear proteomic studies revealed distinct similarities between contact lens
      wearers and dry eye patients. AMO Complete(r) multipurpose contact lens cleaning
      solutions containing taurine seem to have a beneficial effect regarding contact
      lens induced dry eye. To illuminate the effect of taurine on the tear proteome of
      contact lens wearers and sicca patients we developed a gel-based RP-RP capillary
      HPLC-MALDI TOF/TOF MS strategy. Two contact lens wearer groups, one using eye
      drops containing 0.05% taurine; the other for control physiological NaCl solution
      were monitored. Also, a third group of sicca patients using taurine solution was
      studied (N=4 individuals/group). Tear pools of each group at six time points over
      5 weeks were analyzed. In summary 267 tear proteins were identified. We found a
      protein subset showing a linear taurine response with R(2) values >=0.5. Taurine
      effects were detected predominantly in the contact lens group demonstrated by
      distinct level decreases. Most protein candidates were related to inflammation.
      Since levels of these proteins differentiate from those of a healthy non-contact
      lens wearer reference they are supposed to be involved in contact lens induced
      dry eye and should be focused on in further studies.

PMID- 22480907
TI  - Proteomic analysis reveals cellular pathways regulating carbohydrate metabolism
      that are modulated in primary human skeletal muscle culture due to treatment with
      bioactives from Artemisia dracunculus L.
AB  - Insulin resistance is a major pathophysiologic abnormality that characterizes
      metabolic syndrome and type 2 diabetes. A well characterized ethanolic extract of
      Artemisia dracunculus L., termed PMI 5011, has been shown to improve insulin
      action in vitro and in vivo, but the cellular mechanisms remain elusive. Using
      differential proteomics, we have studied mechanisms by which PMI 5011 enhances
      insulin action in primary human skeletal muscle culture obtained by biopsy from
      obese, insulin-resistant individuals. Using iTRAQTM labeling and LC-MS/MS, we
      have identified over 200 differentially regulated proteins due to treatment with
      PMI 5011 and insulin stimulation. Bioinformatics analyses determined that several
      metabolic pathways related to glycolysis, glucose transport and cell signaling
      were highly represented and differentially regulated in the presence of PMI 5011
      indicating that this extract affects several pathways modulating carbohydrate
      metabolism, including translocation of GLUT4 to the plasma membrane. These
      findings provide a molecular mechanism by which a botanical extract improves
      insulin stimulated glucose uptake, transport and metabolism at the cellular level
      resulting in enhanced whole body insulin sensitivity.

PMID- 22480908
TI  - Tick-borne diseases in cattle: applications of proteomics to develop new
      generation vaccines.
AB  - Tick-borne diseases (TBDs) affect 80% of the world's cattle population, hampering
      livestock production throughout the world. Livestock industry is important to
      rural populations not only as food supply, but also as a source of income. Tick
      control is usually achieved by using acaricides which are expensive, deleterious
      to the environment and can induce chemical resistance of vectors; the development
      of more effective and sustainable control methods is therefore required.
      Theileriosis, babesiosis, anaplasmosis and heartwater are the most important TBDs
      in cattle. Immunization strategies are currently available but with variable
      efficacy. To develop a new generation of vaccines which are more efficient,
      cheaper and safer, it is first necessary to better understand the mechanisms by
      which these parasites are transmitted, multiply and cause disease; this becomes
      especially difficult due to their complex life cycles, in vitro culture
      conditions and the lack of genetic tools to manipulate them. Proteomics and other
      complementary post-genomic tools such as transcriptomics and metabolomics in a
      systems biology context are becoming key tools to increase knowledge on the
      biology of infectious diseases. Herein, we present an overview of the so called
      "Omics" studies currently available on these tick-borne pathogens, giving
      emphasis to proteomics and how it may help to discover new vaccine candidates to
      control TBDs.

PMID- 22480909
TI  - Combined snake venomics and venom gland transcriptomic analysis of Bothropoides
      pauloensis.
AB  - Unraveling the repertoire of venom toxins of Bothropoides pauloensis was assessed
      by snake venomics and venom gland transcriptomic surveys. Both approaches yielded
      converging overall figures, pointing to metalloproteinases (~37%), PLA(2)s (26
      32%), and vasoactive (bradykinin-potentiating) peptides (12-17%) as the major
      toxin classes. The high occurrence of SVMPs, PLA(2) molecules, vasoactive
      peptides, along with serine proteinases, explains the local and systemic effects
      observed in envenomations by B. pauloensis. Minor (<3%) C-type lectin, serine
      proteinase, L-amino acid oxidase, nerve growth factor, and CRISP molecules were
      also identified in the transcriptome and the proteome. Low abundance (0.3%) EST
      singletons coding for vascular endothelial growth factor (svVEGF), ohanin,
      hyaluronidase, and 5' nucleotidase were found only in the venom gland cDNA
      library. At the molecular level, the transcriptomic and proteomic datasets
      display low compositional concordance. In particular, although there is good
      agreement between transcriptome and proteome in the identity of BPPs, PLA(2)
      molecules and L-amino acid oxidase, both datasets strongly depart in their C-type
      lectin and SVMP complements. These data support the view that venom composition
      is influenced by transcriptional and translational mechanisms and emphasize the
      value of combining proteomic and transcriptomic approaches to acquire a more
      complete understanding of the toxinological profile and natural history of the
      snake venom.

PMID- 22480910
TI  - Construction of nanometer cisplatin core-ferritin (NCC-F) and proteomic analysis
      of gastric cancer cell apoptosis induced with cisplatin released from the NCC-F.
AB  - Both transmission electron microscopy (TEM) and fluorescence spectrometry were
      used to reveal the characteristics of both subunit disassociation and
      recombination in apo-pig pancreas ferritin (apoPPF) in an alkaline medium ranging
      reversibly from pH 7.0 to 13.0. The experimental results indicated that apoPPF
      could be completely disassociated into 24 free subunits at pH 13.0, and then
      these subunits could be quickly reassembled into the original apoPPF once the pH
      of the reactive medium was returned to pH7.0. This novel and simple method could
      be used to effectively construct a novel nanometer cisplatin core-PPF (NCC-PPF).
      The major characteristics of NCC-PPF were investigated using various analytical
      methods such as ultraviolet-spectrometry, circular dichroism spectrometry and
      TEM, which indicated that its molecular structure was still similar to that of
      the original apoPPF. Results from the inductively coupled plasma mass
      spectrometer (ICP-MS) method showed that 11.26 cisplatin (CDDP) molecules were
      successfully packaged within the NCC-PPF shell, indicating that each molecule of
      apoPPF had the ability to enwrap 11.26 CDDP molecules for constructing the NCC
      PPF. Flow cytometry showed that NCC-PPF also had the ability to release CDDP for
      inducing the apoptosis of gastric cancer cells BGC823 (GCC), but this phenomenon
      could scarcely be observed using apoPPF. A differential proteomic technique using
      two-dimensional electrophoresis (2-DE) gels selected and identified the
      differential proteins from cell apoptosis in order to reveal the molecular
      pathway of GCC apoptosis by both NCC-PPF and free CDDP, giving 13 differential
      expression proteins. These differential proteins could be further classified into
      six groups, which were described as being involved in the regulation of
      apoptosis, RNA transcription, oxidative stress response, signal transduction,
      cell metabolism, and cytoskeleton changes. In addition, a real-time PCR method
      was used to prove the expression level of mRNA and to identify the reliability of
      the protein expression according to these differential proteins, which indicated
      that the mRNA level changes of six differential proteins corresponded to those of
      its differential protein expression in 2-DE gels. These studies played an
      important role in reasonably revealing the different pathways of GCC apoptosis
      induced with both the CDDP released by NCC-PPF and the free CDDP. We thus suggest
      that apoPPF has great potential for constructing a nanometer carrier filled with
      various drugs for application in clinical work.

PMID- 22480911
TI  - Quantifications of dendrochronological information from contrasting
      microdensitometric measuring circumstances of experimental wood samples.
AB  - We analyzed how the pretreatment method of Scots pine (Pinus sylvestris L.) wood
      specimens together with X-ray methodology applied for density analyses affect
      resulting tree-ring data and derived proxy-based climate information. We also
      evaluated whether these results from two contrasting laboratory circumstances
      could be homogenized by applying dendroclimatic statistical methods. For this
      study, we measured a pair of X-ray based microdensitometry datasets using double
      samples of subfossil and recent wood specimens. Dendrochronological information
      of earlywood and latewood series was examined to determine for alterations in the
      resulting data. We found that the level of overall density, its trend over
      cambial ages and the growth amplitude altered due to the sample
      pretreatment/density measuring exercise, which means that comparisons of
      heterogeneous datasets should be, in general, regarded cautiously.
      Dendrochronological standardization did, however, even out several potentially
      biasing influences from the differing overall densities and their trends. The two
      latewood (maximum) density chronologies yielded paleoclimatic reconstructions
      which both calibrated and verified satisfactorily with the instrumental warm
      season (March-September) mean temperatures. The transfer functions were found to
      further equalize the differences between the two proxy records. We recommend (if
      no strictly homogenous data are available) reconciling similar data assemblages
      through transfer functions with multiple independent variables.

PMID- 22480912
TI  - Thermoluminescence study of polyminerals extracted from clove and marjoram for
      detection purposes.
AB  - Food irradiation is a widely employed technology for food treatment. Since in
      several countries no regulations prevail, it is difficult to detect whether food
      has been irradiated or not. Among different analytical methods the study of the
      thermoluminescent (TL) emission of polymineral extracted from food is one of the
      most useful physical identification method. The aim of this work is to analyze
      the TL properties of inorganic polyminerals extracted from commercial clove
      (Syzygium aromaticum L.) and marjoram (Origanum majorana L.) spices exposed to
      (60)Co gamma radiation for detection purposes. The feasibility of using the TL
      method for irradiated food detection and absorbed dose determination is assessed.

PMID- 22480913
TI  - 68Ga-autoclabeling of DOTA-TATE and DOTA-NOC.
AB  - INTRODUCTION: A new method combining (68)Ga-labeling and steam sterilization,
      here called autoclabeling, has been evaluated for two somatostatin receptor
      binding tracers used for positron emission tomography (PET) imaging of
      neuroendocrine tumors; DOTA-TATE and -NOC. METHODS: The two peptides DOTA-TATE
      and -NOC were labeled with (68)Ga by heating for 15 min at 121 degrees C in the
      presence of acetate buffer at pH 4.3. The product solutions were tested for
      sterility, presence of endotoxins, degradation of peptide and osmolality.
      RESULTS: Complete incorporation of (68)Ga was obtained after the autoclabeling
      reaction and no degradation of the peptides was observed. Sterility was verified
      and the presence of endotoxins was well within Ph. Eur limits (175IU/maximum
      injected volume). CONCLUSIONS: The autoclabeling method provides a convenient
      procedure for (68)Ga-labeling by combining the labeling reaction and steam
      sterilization into one single step.

PMID- 22480915
TI  - Response of Northern Elephant Seal platelets to pressure and temperature changes:
      a comparison with human platelets.
AB  - Mammalian blood platelets are activated by physiological agonists such as
      collagen or thrombin, or by physical stimuli such as cold temperatures and rapid
      decompression. Marine mammals regularly experience cold temperatures, high
      pressures and rapid decompression while diving, yet do not appear to suffer from
      thrombotic events during routine dive activity. We evaluated the effects of cold
      temperature and high pressure excursions on Northern Elephant Seal (NES)
      platelets and compared NES platelet response to that of human platelets subjected
      to identical stimuli. NES platelets undergo cold-induced activation when chilled
      to 4  degrees C, and 3 distinct phase transitions can be measured using Fourier
      Transform Infrared Spectroscopy. NES platelet membrane lipid composition was
      determined using thin layer chromatography and NES platelets were found to have
      three times the amount of cholesterol (21% by weight) as human platelets. When
      exposed to high pressure-rapid decompression excursion, NES platelets did not
      undergo morphological shape change nor bind increased amounts of fibrinogen,
      while human platelets were significantly activated by the same excursion. These
      results demonstrate that while NES platelets are activated by the physical
      stimulus of cold temperatures, they are resistant to decompression-induced
      activation. We suggest that the composition of NES platelet membranes may play an
      important role in preventing pressure-related activation.

PMID- 22480914
TI  - Baboon model of generalized epilepsy: continuous intracranial video-EEG
      monitoring with subdural electrodes.
AB  - The baboon provides a natural non-human primate model for photosensitive,
      generalized epilepsy. This study describes an implantation procedure for the
      placement of subdural grid and strip electrodes for continuous video-EEG
      monitoring in the epileptic baboon to evaluate the generation and propagation of
      ictal and interictal epileptic discharges. Subdural grid, strip and depth
      electrodes were implanted in six baboons, targeting brain regions that were
      activated in functional neuroimaging studies during photoparoxysmal responses.
      The baboons were monitored with continuous video-EEG monitoring for 2-21 (mean 9)
      days. Although the animals were tethered, the EEG signal was transmitted
      wirelessly to optimize their mobility. Spontaneous seizures, interictal epileptic
      discharges (IEDs), and responses to intermittent light stimulation (ILS) were
      assessed. Due to cortical injuries related to the electrode implantation and
      their displacement, the procedure was modified. Habitual myoclonic and
      generalized tonic-clonic seizures were recorded in three baboons, all associated
      with a generalized ictal discharge, but were triggered multiregionally, in the
      frontal, parietal and occipital cortices. IEDs were similarly expressed
      multiregionally, and responsible for triggering most generalized spike-and-wave
      discharges. Generalized photoparoxysmal responses were activated only in one
      baboon, while driving responses recorded in all three photosensitive baboons were
      2.5 times the stimulus rate. In contrast to previous intracranial investigations
      in this model, generalized ictal and interictal epileptic discharges were
      triggered by parietal and occipital, in addition to the frontocentral cortices.
      Furthermore, targeted visual areas responded differently to ILS in photosensitive
      than nonphotosensitive baboons, but further studies are required before
      mechanisms can be implicated for ILS-induced activation of the epileptic
      networks.

PMID- 22480916
TI  - [Minimising hospital costs in the treatment of bile duct calculi: a comparison
      study].
AB  - INTRODUCTION: The treatment of bile duct calculi associated with cholelithiasis
      is controversial. The hospital costs could be a decisive factor in choosing
      between the different therapeutic options. OBJECTIVES: To compare the
      effectiveness and costs of two options in the treatment of common bile duct
      calculi: 1) One-stage: Laparoscopic cholecystectomy and bile duct exploration,
      and 2) Two-stage: sequential endoscopic retrograde cholangiopancreatography and
      laparoscopic cholecystectomy. MATERIAL AND METHODS: A retrospective,
      observational study was performed on 49 consecutive patients with bile duct
      calculi and gallbladder in situ, treated consecutively and simultaneously over a
      two year period. The post-operate complication, hospital stay, number of
      procedures per patient, conversion to laparotomy, efficacy of removing the
      calculi, and hospital costs. RESULTS: There were no differences as regards the
      patient clinical features or morbidity. The mean post-surgical hospital stay for
      the One-stage group was less than that in the Two-stage group. Three patients of
      the Two-stage group required conversion to laparotomy. The median costs per
      patient were less for the One-stage strategy, representing an overall saving of
      37,173? during the period studied. CONCLUSIONS: No significant differences were
      found between the two treatment options as regards efficacy or post-surgical
      morbidity and mortality, but there were differences in hospital stay and costs.
      The management of patients with gallstones in one-stage surgery represents a
      saving of 3 days hospital stay and 1,008? per patient.

PMID- 22480917
TI  - Site directed vascular gene delivery in vivo by ultrasonic destruction of
      magnetic nanoparticle coated microbubbles.
AB  - Site specific vascular gene delivery for therapeutic implications is favorable
      because of reduction of possible side effects. Yet this technology faces numerous
      hurdles that result in low transfection rates because of suboptimal delivery.
      Combining ultrasonic microbubble technology with magnetic nanoparticle enhanced
      gene transfer could make it possible to use the systemic vasculature as the route
      of application and to magnetically trap these compounds at the target of
      interest. In this study we show that magnetic nanoparticle-coated microbubbles
      bind plasmid DNA and successfully deliver it to endothelial cells in vitro and
      more importantly transport their cargo through the vascular system and
      specifically deliver it to the vascular wall in vivo at sites where microbubbles
      are retained by magnetic force and burst by local ultrasound application. This
      resulted in a significant enhancement in site specific gene delivery compared
      with the conventional microbubble technique. Thus, this technology may have
      promising therapeutic potential. FROM THE CLINICAL EDITOR: This work focuses on
      combining ultrasonic microbubble technology with magnetic nanoparticle enhanced
      gene transfer to enable targeted gene delivery via the systemic vasculature and
      magnetic trapping of these compounds at the target of interest.

PMID- 22480919
TI  - Genetics of atherosclerosis.
AB  - Genome-wide association studies (GWAS) from the past several years have provided
      the first unbiased evidence of the genes contributing to common cardiovascular
      disease traits in European and some Asian populations. The results not only
      confirmed the importance of prior knowledge, such as the central role of
      lipoproteins, but also revealed that there is still much to learn about the
      underlying mechanisms of this disease, as most of the associated genes do not
      appear to be involved in pathways previously connected to atherosclerosis. In
      this review, I focus on the common forms of the disease and look at both human
      and animal model studies. I summarize what was known before GWAS, highlight how
      the field has been changed by GWAS, and discuss future considerations, such as
      the limitations of GWAS and strategies that may lead to a more complete,
      mechanistic understanding of atherosclerosis.

PMID- 22480918
TI  - Pathway analysis of genomic data: concepts, methods, and prospects for future
      development.
AB  - Genome-wide data sets are increasingly being used to identify biological pathways
      and networks underlying complex diseases. In particular, analyzing genomic data
      through sets defined by functional pathways offers the potential of greater power
      for discovery and natural connections to biological mechanisms. With the
      burgeoning availability of next-generation sequencing, this is an opportune
      moment to revisit strategies for pathway-based analysis of genomic data. Here, we
      synthesize relevant concepts and extant methodologies to guide investigators in
      study design and execution. We also highlight ongoing challenges and proposed
      solutions. As relevant analytical strategies mature, pathways and networks will
      be ideally placed to integrate data from diverse -omics sources to harness the
      extensive, rich information related to disease and treatment mechanisms.

PMID- 22480921
TI  - Reduction in skin grafting after the introduction of hydrofiber dressings in
      partial thickness burns: a comparison between a hydrofiber and silver
      sulphadiazine.
AB  - AIM/PURPOSE: The aim of this study was to compare clinical outcome of children
      with scald burns treated with a hydrofiber dressing (Aquacel((r)), Convatec Inc.)
      with the former standard of care with silver sulfadiazine (Flammazine((r));
      Solvay Pharmaceuticals), considering surgical intervention and length of stay
      (LOS). METHODS: A retrospective study of all consecutive children from zero to
      four years with primary scald burns up to 10% admitted to the Burn Centre of the
      Maasstad Hospital Rotterdam between January 1987 and January 2010 were reviewed.
      For data collection a prospective computerized database was used. For comparison
      the study period was divided into two periods representing the period before and
      after the introduction of the hydrofiber dressing (HFD), respectively 1987-1999
      (period 1) and 1999-2010 (period 2). RESULTS: Over the whole study period 27.3%
      of 502 patients treated with silver sulfadiazine (Ag-SD) underwent surgery, while
      before the introduction of HFD 30.5% of 338 Ag-SD treated patients were operated
      upon. After the introduction of the HFD 20.7% of 164 patients treated with Ag-SD
      eventually underwent skin grafting, a significant difference with the 11.6% of
      302 patients whose wounds were dressed with HFD (p<0.01). CONCLUSIONS: Compared
      to silver sulfadiazine treatment a reduced number of surgical interventions was
      observed in mixed partial thickness scald burns up to 10% TBSA burned in children
      aged 0-4 years after the introduction of hydrofiber dressings. The mode of
      treatment with this wound dressing also limited hospital length of stay.

PMID- 22480920
TI  - Causes and consequences of the evolution of reproductive mode in Caenorhabditis
      nematodes.
AB  - Reproduction is directly connected to the suite of developmental and
      physiological mechanisms that enable it, but how it occurs also has consequences
      for the genetics, ecology and longer term evolutionary potential of a lineage. In
      the nematode Caenorhabditis elegans, anatomically female XX worms can self
      fertilize their eggs. This ability evolved recently and in multiple
      Caenorhabditis lineages from male-female ancestors, providing a model for
      examining both the developmental causes and longer term consequences of a novel,
      convergently evolved reproductive mode. Here, we review recent work that
      implicates translation control in the evolution of XX spermatogenesis, with
      different selfing lineages possessing both reproducible and idiosyncratic
      features. We also discuss the consequences of selfing, which leads to a rapid
      loss of variation and relaxation of natural and sexual selection on mating
      related traits, and may ultimately put selfing lineages at a higher risk of
      extinction.

PMID- 22480923
TI  - Western driving regulations for unprovoked first seizures and epilepsy.
AB  - PURPOSE: To review the legislation for non-commercial driving licenses in the
      Western world for unprovoked first seizures (UFS) and recurrence of established
      epilepsy, and to examine available evidence on the road traffic accident (RTA)
      risk in people with seizures. METHODS: Regulations for non-commercial driving
      licenses were sought from appropriate national or state authorities and epilepsy
      societies. The literature was searched for consensus guidelines and data relevant
      to risk analysis, including an appropriate seizure-free period (SFP). RESULTS:
      The SFP varied widely from 3 to 24 months and in most countries no distinction
      was made between UFS and recurrence of established epilepsy. In the European
      Union (EU), harmonisation is underway but implementation of the relevant
      directive has been slow. The excess risk of RTA in epilepsy is minimal,
      especially compared to other factors such as alcohol, and few accidents result
      from seizures at the wheel. Risk analysis supports the shortened SFPs that are
      being enacted in the EU. CONCLUSION: Regulations across the world continue to
      vary widely, and the available data support rules which are less stringent than
      those currently in force in many parts of the Western world. The ongoing European
      harmonisation is encouraging but much work remains to be done in revising
      legislation elsewhere, and in strengthening the theoretical foundations
      underpinning driving regulations.

PMID- 22480924
TI  - Canine rabies vaccination and domestic dog population characteristics in the
      developing world: a systematic review.
AB  - BACKGROUND: Human rabies remains a significant problem in many developing
      countries, where canine rabies is the most common means of transmission. Although
      vaccination of dogs has been shown to be the most effective method of prevention
      in humans, dog vaccination is often lacking. METHODS: This systematic review
      examined dog rabies vaccination coverage achieved following mass vaccination
      campaigns and dog ecology/management factors relevant to rabies control in the
      developing world. We searched a variety of electronic databases for published
      articles pertaining to dog rabies vaccination or dog ecology where data were
      collected utilizing a household cluster survey. We reviewed studies published
      between January 1, 1980 and present and identified 29 articles for inclusion.
      RESULTS: We found the majority of vaccination campaigns were able to achieve the
      WHO recommended vaccination coverage of >= 70% and calculated weighted mean post
      campaign vaccination coverage of 76.5% in urban areas and 73.7% in rural areas.
      However, we found an absence of studies related to dog vaccination/dog ecology
      from countries with the greatest burden of rabies such as India, China, and
      Pakistan. In addition, the majority of dogs in the developing world are very
      young and short-lived, reducing the effectiveness of vaccination campaigns.
      CONCLUSIONS: Future studies on canine ecology should be undertaken in countries
      with high endemic canine rabies. New methods for improving the longevity of dogs
      and reducing high dog population turnover need to be investigated. Programs which
      encourage good dog management and promote responsible pet ownership are essential
      to eliminating canine and human rabies.

PMID- 22480925
TI  - Potential overestimation of HPV vaccine impact due to unmasking of non-vaccine
      types: quantification using a multi-type mathematical model.
AB  - INTRODUCTION: Estimates of human papillomavirus (HPV) vaccine impact in clinical
      trials and modelling studies rely on DNA tests of cytology or biopsy specimens to
      determine the HPV type responsible for a cervical lesion. DNA of several
      oncogenic HPV types may be detectable in a specimen. However, only one type may
      be responsible for a particular cervical lesion. Misattribution of the causal HPV
      type for a particular abnormality may give rise to an apparent increase in
      disease due to non-vaccine HPV types following vaccination ("unmasking").
      METHODS: To investigate the existence and magnitude of unmasking, we analysed
      data from residual cytology and biopsy specimens in English women aged 20-64
      years old using a stochastic type-specific individual-based model of HPV
      infection, progression and disease. The model parameters were calibrated to data
      on the prevalence of HPV DNA and cytological lesion of different grades, and used
      to assign causal HPV types to cervical lesions. The difference between the
      prevalence of all disease due to non-vaccine HPV types, and disease due to non
      vaccine HPV types in the absence of vaccine HPV types, was then estimated.
      RESULTS: There could be an apparent maximum increase of 3-10% in long-term
      cervical cancer incidence due to non-vaccine HPV types following vaccination.
      CONCLUSION: Unmasking may be an important phenomenon in HPV post-vaccination
      epidemiology, in the same way that has been observed following pneumococcal
      conjugate vaccination.

PMID- 22480926
TI  - Progressive changes in pneumococcal carriage in children attending daycare in
      Portugal after 6 years of gradual conjugate vaccine introduction show falls in
      most residual vaccine serotypes but no net replacement or trends in diversity.
AB  - OBJECTIVES: To track ongoing trends in pneumococcal (Sp) serotype carriage under
      the selection pressure of moderate pneumococcal conjugate vaccine (PCV) use,
      children in a community in Portugal were studied in the same months in 3
      consecutive years. METHODS: Nasopharyngeal specimens were collected (children
      aged 3 months to <7 years) in 8 urban daycare centers in February 2008 (n=561)
      and 2009 (n=585). Sp isolates were serotyped. RESULTS: While demographics were
      similar in 2008-2009 and a previously reported sample in 2007, PCV coverage (at
      least one dose) in the children studied rose from 76.5% to 84% although national
      coverage was lower than this. Sp carriage fell from 61% to 51% with a concomitant
      fall in PCV7 serotype carriage from 12.1% to 4.3%. Remaining PCV7 serotypes
      declined to near (23F) or totally (6B, 14) undetectable levels except 19F which
      persisted unchanged in around 4% of children. Although carriage of 3 and 6C rose,
      there was no net increase in non-PCV7 serotypes and no progressive trend in
      serotype diversity. CONCLUSIONS: Ecological changes induced by PCVs where uptake
      is moderate appear to be different from high usage settings. We report falling Sp
      carriage due to PCV7 serotype disappearance with persistence of 19F and no
      ongoing net replacement after several years of PCV7 use and slowly rising uptake.

PMID- 22480927
TI  - An update on human papillomavirus vaccine uptake among 11-17 year old girls in
      the United States: National Health Interview Survey, 2010.
AB  - PURPOSE: A 3-dose human papillomavirus (HPV) vaccine is recommended for
      adolescents to protect against HPV-related cervical and other cancers. The
      purpose of this study was to provide an update on HPV vaccine uptake among 11-17
      year old girls residing in the US. METHODS: Data from the 2010 National Health
      Interview Survey (NHIS) were obtained to assess HPV vaccination status and its
      correlates. Multivariate logistic regression analyses were performed to examine
      HPV vaccine uptake of >= 1 dose and >= 3 doses among all girls, and completion of
      the 3-dose series among those who initiated (received >= 1 dose) the vaccine.
      RESULTS: Overall, 28.9% and 14.2% received >= 1 dose and >= 3 doses of vaccine:
      14.5% and 3.0% among 11-12 year old girls, and 34.8% and 18.7% among 13-17 year
      olds, respectively. Hispanics had higher uptake of >= 1 dose (odds ratio (OR)
      1.63, 95% confidence interval (CI) 1.22-2.17) than whites. Having received an
      influenza shot in the past year and parents' awareness of the vaccine were
      significantly associated with receiving >= 1 dose (OR 1.88, 95% CI 1.51-2.33 and
      OR 16.57, 95% CI 10.95-25.06) and >= 3 doses (OR 1.48, 95% CI 1.13-1.92 and OR
      10.60, 95% CI 5.95-18.88). A separate multivariate model based on girls who
      initiated the vaccine did not identify any significant correlates of 3-dose
      series completion. Among parents of unvaccinated girls, 60% were not interested
      in vaccinating their daughters and mentioned three main reasons: "does not need
      vaccine" (25.5%), "worried about safety" (19.3%) and "does not know enough about
      vaccine" (16.6%). Of those who were interested, 53.7% would pay $360-$500 for the
      vaccination, while 41.7% preferred to receive it at a much lower cost or free.
      CONCLUSIONS: Only 1 out of 3 girls (11-17 years) have received >= 1 dose of HPV
      vaccine and much less have completed all 3 doses. Strategies should be taken to
      improve this vaccine uptake among girls, especially those 11-12 year olds, and to
      educate parents about the importance of vaccination.

PMID- 22480928
TI  - Factors associated with HPV vaccine uptake in teenage girls: a systematic review.
AB  - BACKGROUND: Since 2006 Human papillomavirus (HPV) vaccination has become
      available to adolescent girls and women in an increasing number of countries, to
      protect against the virus causing cervical cancer. The vaccine series is offered
      in three doses over 6 months, and this study aimed to identify factors associated
      with initiation and/or completion of the 3 dose series in (pre-) adolescent
      girls. Previous studies have considered intention to vaccinate rather than actual
      vaccination uptake. METHODS: A systematic search of Medline, Medline in process,
      Embase and CINAHL, from 2006 to March 2011 for articles related to HPV-vaccine
      uptake among adolescent girls and factors potentially associated with uptake
      yielded 25 studies. RESULTS: The majority of studies were surveys or
      retrospective reviews of data, only 5 studies reported data on program
      completion. Most were conducted in the United States (20/25). Higher vaccine
      uptake was associated with having health insurance, of older age, receipt of
      childhood vaccines, a higher vaccine related knowledge, more healthcare
      utilization, having a healthcare provider as a source of information and positive
      vaccine attitudes. In US settings, African American girls were less likely to
      have either initiated or completed the three dose vaccination series.
      CONCLUSIONS: HPV vaccination programs should focus on narrowing disparities in
      vaccine receipt in ethnic and racial groups and on providing correct information
      by a reliable source, e.g. healthcare providers. School-based vaccination
      programs have a high vaccine uptake. More studies are required to determine
      actual vaccine course completion and factors related to high uptake and
      completion, and information from a broader range of developed and developing
      settings is needed.

PMID- 22480929
TI  - Myeloid dendritic cells loaded with dendritic tandem multiple antigenic
      telomerase reverse transcriptase (hTERT) epitope peptides: a potentially
      promising tumor vaccine.
AB  - Human telomerase reverse transcriptase (hTERT) has been identified as an ideal
      tumor-associated antigen (TAA). Use of a synthetic hTERT epitope peptide to pulse
      dendritic cells can induce autologous T cell anti-tumor immune responses, but
      such responses induced by a single epitope peptide have been shown to be weak and
      a narrow-spectrum. Here, we designed dendritic tandem multiple antigenic peptides
      (MAPs) containing the following three hTERT epitope peptides: I540, V461 and
      L766, which are HLA-A*02-, HLA-A*24- and HLA-RDB1*04/11/15-restricted,
      respectively. The MAPs and their three single-epitope peptides were obtained
      through solid-phase synthesis. Healthy volunteers that were HLA-A*02(+)/HLA
      DRB1*04(+) and HLA-A*24(+)/HLA-DRB1*15(+) were recruited. Myeloid dendritic cells
      were isolated by magnetic activated cell sorting and were divided into a MAP
      stimulated group (MAP-DC), a group in which the three epitope peptides were mixed
      and used to stimulate the DCs (MixP-DC) and a no peptide-stimulated group (NoP
      DC, control group). All of the DCs were cultured in serum-free medium, pulsed
      with the corresponding peptides on the 3rd, 5th and 7th days, and co-cultured
      with autologous lymphocytes when they were mature. The related cytokines were
      measured via ELISA. The killing effects of cytotoxic T lymphocytes (CTLs) on
      SW480/A549 tumor cells expressing HLA-A*02(+), HepG2/SMMC-7721 cells expressing
      HLA-A*24(+) and SKOV3 cells negative for HLA-A*02/A*24 were detected by flow
      cytometry. Our results indicated that the CTLs induced by the MAP-DCs had the
      greatest anti-tumor effect. Therefore, the dendritic tandem multiple antigenic
      hTERT epitope peptides combined with MDCs may represent a powerful, broad
      spectrum anti-tumor vaccine.

PMID- 22480930
TI  - Coxiella symbiont in the tick Ornithodoros rostratus (Acari: Argasidae).
AB  - In the present study, the presence of tick-associated bacteria and protozoa in
      Ornithodoros rostratus ticks (adults, nymphs, and eggs) from the Pantanal region
      of Brazil were determined by molecular detection. In these ticks, DNA from
      protozoa in the genera Babesia and Hepatozoon, and bacteria from the genera
      Rickettsia, Borrelia, Anaplasma, and Ehrlichia were not detected. Conversely, all
      tested ticks (100%) yielded PCR products for 3 Coxiella genes (16S rRNA, pyrG,
      cap). PCR and phylogenetic analysis of 3 amplified genes (16S rRNA, pyrG, cap)
      demonstrated that the agent infecting O. rostratus ticks was a member of the
      genus Coxiella. This organism grouped with Coxiella symbionts of other soft tick
      species (Argasidae), having different isolates of C. burnetii as a sister group,
      and these 2 groups formed a clade that grouped with another clade containing
      Coxiella symbionts of hard tick species (Ixodidae). Analysis of tick
      mitochondrial 16S rRNA gene database composed mostly of tick species previously
      shown to harbor Coxiella symbionts suggests a phylogenetic congruence of ticks
      and their Coxiella symbionts. Furthermore, these results suggest a very long
      period of coevolution between ticks and Coxiella symbionts and indicates that the
      original infection may have occurred in an ancestor common to the 2 main tick
      families, Argasidae (soft ticks) and Ixodidae (hard ticks). However, this
      evolutionary relationship must be confirmed by more extensive testing of
      additional tick species and expanded populations.

PMID- 22480932
TI  - Motif switches: decision-making in cell regulation.
AB  - Tight regulation of gene products from transcription to protein degradation is
      required for reliable and robust control of eukaryotic cell physiology. Many of
      the mechanisms directing cell regulation rely on proteins detecting the state of
      the cell through context-dependent, tuneable interactions. These interactions
      underlie the ability of proteins to make decisions by combining regulatory
      information encoded in a protein's expression level, localisation and
      modification state. This raises the question, how do proteins integrate available
      information to correctly make decisions? Over the past decade pioneering work on
      the nature and function of intrinsically disordered protein regions has revealed
      many elegant switching mechanisms that underlie cell signalling and regulation,
      prompting a reevaluation of their role in cooperative decision-making.

PMID- 22480931
TI  - Mitochondrial Ca(2+) and apoptosis.
AB  - Mitochondria are key decoding stations of the apoptotic process. In support of
      this view, a large body of experimental evidence has unambiguously revealed that,
      in addition to the well-established function of producing most of the cellular
      ATP, mitochondria play a fundamental role in triggering apoptotic cell death.
      Various apoptotic stimuli cause the release of specific mitochondrial pro
      apoptotic factors into the cytosol. The molecular mechanism of this release is
      still controversial, but there is no doubt that mitochondrial calcium (Ca(2+))
      overload is one of the pro-apoptotic ways to induce the swelling of mitochondria,
      with perturbation or rupture of the outer membrane, and in turn the release of
      mitochondrial apoptotic factors into the cytosol. Here, we review as different
      proteins that participate in mitochondrial Ca(2+) homeostasis and in turn
      modulate the effectiveness of Ca(2+)-dependent apoptotic stimuli. Strikingly, the
      final outcome at the cellular level is similar, albeit through completely
      different molecular mechanisms: a reduced mitochondrial Ca(2+) overload upon pro
      apoptotic stimuli that dramatically blunts the apoptotic response.

PMID- 22480933
TI  - Agonist-bound structures of G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) play a major role in intercellular
      communication by binding small diffusible ligands (agonists) at the extracellular
      surface. Agonist-binding induces a conformational change in the receptor, which
      results in the binding and activation of heterotrimeric G proteins within the
      cell. Ten agonist-bound structures of non-rhodopsin GPCRs published last year
      defined for the first time the molecular details of receptor activated states and
      how inverse agonists, partial agonists and full agonists bind to produce
      different effects on the receptor. In addition, the structure of the beta(2)
      adrenoceptor coupled to a heterotrimeric G protein showed how the opening of a
      cleft in the cytoplasmic face of the receptor as a consequence of agonist binding
      results in G protein coupling and activation of the G protein.

PMID- 22480934
TI  - New evidence for the involvement of mitochondrial inheritance in schizophrenia:
      results from a cross-sectional study evaluating the risk of illness in relatives
      of schizophrenia patients.
AB  - OBJECTIVE: One of the hypotheses about the genetic factors that contribute to
      schizophrenia involves mitochondrial DNA (mtDNA), an approximately 16,569-base
      pair molecule inherited only from the mother. If this hypothesis were true, one
      would expect a higher frequency of schizophrenia among matrilineal relatives who
      share mtDNA with a schizophrenia patient than among relatives who do not. This
      article reports the risk of presenting with schizophrenia, other psychiatric
      disorders, and conditions related to mitochondrial disorders in relatives who
      share mtDNA with a schizophrenia patient versus those who do not. METHOD: We
      interviewed 100 schizophrenia patients (DSM-IV criteria) and 147 of their first
      degree relatives from November 2007 to November 2009 to collect clinical data
      from patients and from both sides of each patient's pedigree. The study was
      conducted at of a psychiatric teaching hospital in Reus, Spain. Contingency
      tables were established, and odds ratios were calculated to estimate relative
      risk. RESULTS: Relatives who shared mtDNA with a schizophrenia patient had a
      higher risk of presenting with schizophrenia than those who did not share mtDNA
      (odds ratio [OR] = 3.05; 95% CI, 1.65-5.72; P < .001). Female but not male
      relatives who shared mtDNA with a schizophrenia patient also had a higher risk of
      unipolar depression (OR =10.19; 95% CI, 4.07-32.80; P < .001), panic attack (OR =
      15.52; 95% CI, 2.41-643.6; P < .001), and other anxiety disorders (OR = 4.14; 95%
      CI, 1.84-9.71; P < .001). Some conditions frequently associated with
      mitochondrial disorders were also more frequent among female relatives who shared
      mtDNA with a schizophrenia patient than among those who did not. CONCLUSIONS: The
      results of this study support the hypothesis that mtDNA may be involved in
      schizophrenia. In females, mtDNA could also be involved in the development of
      other psychiatric and nonpsychiatric conditions. Further studies are needed to
      confirm the role of mtDNA in psychiatric disorders.

PMID- 22480935
TI  - Satellite imaging coral reef resilience at regional scale. A case-study from
      Saudi Arabia.
AB  - We propose a framework for spatially estimating a proxy for coral reef resilience
      using remote sensing. Data spanning large areas of coral reef habitat were
      obtained using the commercial QuickBird satellite, and freely available imagery
      (NASA, Google Earth). Principles of coral reef ecology, field observation, and
      remote observations, were combined to devise mapped indices. These capture
      important and accessible components of coral reef resilience. Indices are divided
      between factors known to stress corals, and factors incorporating properties of
      the reef landscape that resist stress or promote coral growth. The first-basis
      for a remote sensed resilience index (RSRI), an estimate of expected reef
      resilience, is proposed. Developed for the Red Sea, the framework of our analysis
      is flexible and with minimal adaptation, could be extended to other reef regions.
      We aim to stimulate discussion as to use of remote sensing to do more than simply
      deliver habitat maps of coral reefs.

PMID- 22480937
TI  - Aortic coarctation misdiagnosed as a descending thoracic aorta aneurysm.
AB  - Aortic coarctation (AC) represents -7% of congenital cardiac diseases and is
      usually diagnosed in childhood or early adult Life, depending on the severity of
      obstruction and associated malformations. Left untreated fewer than 20% of
      patients survive to age 50. We describe a case of thoracic AC, diagnosed at age
      61, in a woman with known hypertension since age 45. At age 56 the patient was
      admitted with a subarachnoid hemorrhage and, during cerebral angiography, a
      thoracic aortic aneurysm was detected. Four years later the patient was referred
      to the outpatient hypertension clinic due to uncontrolled hypertension and
      cardiac failure. The echocardiogram disclosed left ventricular hypertrophy and
      aggressive treatment failed to control her hypertension. At age 61, due to lower
      limb muscular fatigue, arterial Doppler ultrasound was performed that revealed
      symmetrically decreased ankle/brachial pressure index, suggesting aortic
      stenosis. MRI angiography enabled a diagnosis of AC with a large poststenotic
      dilation which had been interpreted as an aortic aneurysm in successive CT scans.
      The authors highlight the unusually late clinical presentation and misdiagnosis
      despite extensive radiologic investigation. The subarachnoid hemorrhage was
      probably a disease manifestation, since berry aneurysms are among the noncardiac
      malformations associated with AC.

PMID- 22480936
TI  - Research advances in plant-made flavivirus antigens.
AB  - Outbreaks of flaviviruses such as dengue (DV), yellow fever (YFV), Japanese
      encephalitis (JEV), tick-borne encephalitis (TBEV) and West Nile (WNV) affect
      numerous countries around the world. The fast spread of these viruses is the
      result of increases in the human population, rapid urbanisation and
      globalisation. While vector control is an important preventive measure against
      vector-borne diseases, it has failed to prevent the spread of these diseases,
      particularly in developing countries where the implementation of control measures
      is intermittent. As antiviral drugs against flaviviruses are not yet available,
      vaccination remains the most important tool for prevention. Although human
      vaccines for YFV, TBEV and JEV are available, on-going vaccination efforts are
      insufficient to prevent infection. No vaccines against DENV and WNV are
      available. Research advances have provided important tools for flavivirus vaccine
      development, such as the use of plants as a recombinant antigen production
      platform. This review summarises the research efforts in this area and highlights
      why a plant system is considered a necessary alternative production platform for
      high-tech subunit vaccines.

PMID- 22480938
TI  - [Renal oncocytoma in pregnancy--an unusual presentation of secondary
      hypertension].
AB  - INTRODUCTION: Renal oncocytoma accounts for 5-7% of primary renal neoplasms. It
      is usually, diagnosed in asymptomatic patients and is characterized by a benign
      behavior without invasion of adjacent tissues or metastasis. Diagnosis during
      pregnancy is uncommon and to date there have been only a few cases reported in
      the literature. CASE REPORT: The authors present the case of a 32-year-old
      nulliparous woman with uncontrolled hypertension diagnosed at seven weeks
      gestation. She was referred to our institution at 24 weeks with superimposed pre
      eclampsia complicated by acute pulmonary edema and hemodynamic instability
      requiring mechanical ventilatory support, fetal growth restriction and
      stillbirth. Etiological study of the hypertensive disorder performed in the
      postpartum period was consistent with renal oncocytoma. CONCLUSION: The clinical
      behavior of renal oncocytoma remains poorly characterized during pregnancy and
      may lead to an adverse maternal and fetal outcome despite its theoretically
      benign behavior. It is essential to exclude a possible secondary cause of
      hypertension in cases that are difficult to control.

PMID- 22480939
TI  - Biodegradation and detoxification of olive mill wastewater by selected strains of
      the mushroom genera Ganoderma and Pleurotus.
AB  - Thirty-nine white-rot fungi belonging to nine species of Agaricomycotina
      (Basidiomycota) were initially screened for their ability to decrease olive-mill
      wastewater (OMW) phenolics. Four strains of Ganoderma australe, Ganoderma
      carnosum, Pleurotus eryngii and Pleurotus ostreatus, were selected and further
      examined for key-aspects of the OMW biodegradation process. Fungal growth in OMW
      containing batch cultures resulted in significant decolorization (by 40-46% and
      60-65% for Ganoderma and Pleurotus spp. respectively) and reduction of phenolics
      (by 64-67% and 74-81% for Ganoderma and Pleurotus spp. respectively). COD
      decrease was less pronounced (12-29%). Cress-seeds germination increased by 30
      40% when OMW was treated by Pleurotus strains. Toxicity expressed as inhibition
      of Aliivibrio fischeri luminescence was reduced in fungal-treated OMW samples by
      approximately 5-15 times compared to the control. As regards the pertinent enzyme
      activities, laccase and Mn-independent peroxidase were detected for Ganoderma
      spp. during the entire incubation period. In contrast, Pleurotus spp. did not
      exhibit any enzyme activities at early growth stages; instead, high laccase (five
      times greater than those of Ganoderma spp.) and Mn peroxidases activities were
      determined at the end of treatment. OMW decolorization by Ganoderma strains was
      strongly correlated to the reduction of phenolics, whereas P. eryngii laccase
      activity was correlated with the effluent's decolorization.

PMID- 22480940
TI  - Impact of genetic diversity and inbreeding on the life-history of Chironomus
      midges over consecutive generations.
AB  - We report results of a multigenerational experiment with Chironomus riparius. Two
      strains with a high and a low level of genetic variability were exposed to a low,
      environmentally relevant TBT concentration of 80 MUg Sn kg(-1)sedimentdw
      nominally (time weighted mean, based on measured concentrations: 4.5 MUg Sn kg(
      1)sedimentdw), and various life history traits as well as genetic diversity were
      monitored for eleven consecutive generations. While TBT effects are hardly
      visible in the outbred and genetically diverse strain, the inbred and genetically
      impoverished strain shows a clearly reduced population growth rate compared to
      the control. Moreover, the impoverished strain shows an increase in fitness over
      time. Analyses of variation at five microsatellite loci revealed that the level
      of genetic variation is strongly reduced in the inbred compared to the outbred
      strain. Moreover, genetic diversity increases over time in the inbred strain.
      This finding explains the observed increase in fitness in both inbred lineages
      (control and TBT exposed). The results document that inbreeding and the level of
      genetic diversity might be of crucial importance in populations under pollution
      stress. Furthermore, ecotoxicological bioassays have to consider genetic
      diversity if results between laboratories should be comparable. Our data provides
      evidence that genetic diversity strongly contributes to the survival of a
      population exposed to chemical pollution.

PMID- 22480941
TI  - Release of pentachlorophenol from black carbon-inclusive sediments under
      different environmental conditions.
AB  - To investigate the feasibility of using black carbon (BC) in the control of
      hydrophobic organic contaminants (HOCs) in sediment, we added BCs from various
      sources (rice straw charcoal (RC), fly ash (FC) and soot (SC)) to sediment to
      create different BC-inclusive sediments and studied the release of
      pentachlorophenol (PCP) in the sediments under different condition. Different pH
      values had no obvious effect on the release of PCP in BC-inclusive sediment, but
      solid/liquid ratio, temperature, salinity and dissolved organic matter (DOM)
      content had significant influences on the release of PCP in all sediments except
      the RC-inclusive sediment. Adding 2% RC to sediment resulted in a 90% decrease in
      PCP release, which was a greater decrease than observed with FC- and SC-inclusive
      sediments. Therefore, from the standpoint of HOC release, the application of RC
      is feasible for organic pollution control in the water environment.

PMID- 22480942
TI  - Spatial trend and pollution assessment of total mercury and methylmercury
      pollution in the Pearl River Delta soil, South China.
AB  - Total mercury (THg) and methylmercury (MeHg) were measured in large number of
      soil samples collected from areas with different types of land use, different
      depth in the Pearl River Delta (PRD) of South China. THg and MeHg concentrations
      ranged from 16.7 to 3320ngg(-1) and 0.01 to 1.34ngg(-1), respectively. THg levels
      are highest in the top 0-20cm soil layer, and decrease from the surface to bottom
      layer soil. Spatial variation was observed with different types of land use.
      Urban parks had the highest concentrations and the other areas tended to decrease
      in the order of residential areas, industrial areas, vegetable fields, cereal
      fields, and woodlands. Temporal variation was also noted, and two relatively high
      THg contamination zones located in the northwestern part of the PRD have
      significantly expanded over the last two decades. Both THg and MeHg
      concentrations were correlated significantly with soil organic matter (OM), but
      not with soil pH. THg pollution status was evaluated using two assessment
      methods.

PMID- 22480943
TI  - Determination of detoxification to Daphnia magna of four pharmaceuticals and
      seven surfactants by activated sludge.
AB  - Pharmaceuticals are bioactive compounds generally resistant to biodegradation,
      which can make them problematic when they are released into nature. The use
      pattern for pharmaceuticals means that they are discharged into water via sewage
      treatment plants. Also surfactants are discharged through sewage treatment
      plants, primarily due to their use in detergents and shampoos and other cleaners.
      In this study the acute toxicity to Daphnia magna of four pharmaceuticals
      (ciprofloxacin, ibuprofen, paracetamol and zinc pyrithione) and seven surfactants
      (C8 alkyl glucoside, C6 alkyl glucoside, sodium caprylimidiopropionate, tallow
      trimethyl-ammonium chloride, potassium decylphosphate, propylheptanol ethoxylate
      and alkylmonoethanolamide ethoxylate) was determined. Abiotic (without activated
      sludge bacteria) and biotic (with activated sludge bacteria) detoxification was
      also determined. The 24-h EC50s ranged from 2 MUg L(-1) for the most toxic
      substance (zinc pyrithione) to 2 g L(-1) for the least toxic compound (C6 alkyl
      glucoside). Detoxification rates determined as the ratio between initial EC50 and
      EC50 after 1 week in water with activated sludge bacteria ranged from 0.4
      (paracetamol) to 13 (zinc pyrithione). For most of these chemicals detoxification
      rate decreased after 1 week, but for one (alkylmonoethanolamide ethoxylate) it
      increased from about 2 to 30 times after 2 weeks. Many of these chemicals were
      "detoxified" also abiotically at about the same rate as biotically. Further
      studies are needed to determine the degradation products that were precipitated
      (aggregated) for some of the tested chemicals. Altogether, this study has shown
      that there are large differences in toxicity among chemicals entering sewage
      treatment plants, but also that the detoxification of them can differ. Therefore,
      the detoxification should receive more attention in the hazard and risk
      assessment of chemicals entering sewage treatment plants.

PMID- 22480944
TI  - Theoretical and experimental characterisation of magnetic microbubbles.
AB  - In addition to improving image contrast, microbubbles have shown great potential
      in molecular imaging and drug/gene delivery. Previous work by the authors showed
      that considerable improvements in gene transfection efficiency were obtained
      using microbubbles loaded with magnetic nanoparticles under simultaneous exposure
      to ultrasound and magnetic fields. The aim of this study was to characterise the
      effect of nanoparticles on the dynamic and acoustic response of the microbubbles.
      High-speed video microscopy indicated that the amplitude of oscillation was very
      similar for magnetic and nonmagnetic microbubbles of the same size for the same
      ultrasound exposure (0.5 MHz, 100 kPa, 12-cycle pulse) and that this was
      minimally affected by an imposed magnetic field. The linear scattering to
      attenuation ratio (STAR) was also similar for suspensions of both bubble types
      although the nonlinear STAR was ~50% lower for the magnetic microbubbles. Both
      the video and acoustic data were supported by the results from theoretical
      modelling.

PMID- 22480945
TI  - Effect of acetate formation pathway and long chain fatty acid CoA-ligase on the
      free fatty acid production in E. coli expressing acy-ACP thioesterase from
      Ricinus communis.
AB  - Microbial biosynthesis of fatty acid like chemicals from renewable carbon sources
      has attracted significant attention in recent years. Free fatty acids can be used
      as precursors for the production of fuels or chemicals. Wild type E. coli strains
      produce fatty acids mainly for the biosynthesis of lipids and cell membranes and
      do not accumulate free fatty acids as intermediates in lipid biosynthesis.
      However, free fatty acids can be produced by breaking the fatty acid elongation
      through the overexpression of an acyl-ACP thioesterase. Since acetyl-CoA might be
      an important factor for fatty acid synthesis (acetate formation pathways are the
      main competitive pathways in consuming acetyl-CoA or pyruvate, a precursor of
      acetyl-CoA), and the long chain fatty acid CoA-ligase (FadD) plays a pivotal role
      in the transport and activation of exogenous fatty acids prior to their
      subsequent degradation, we examined the composition and the secretion of the free
      fatty acids in four different strains including the wild type MG1655, a mutant
      strain with inactivation of the fatty acid beta-oxidation pathway (fadD mutant
      (ML103)), and mutant strains with inactivation of the two major acetate
      production pathways (an ack-pta (acetate kinase/phosphotransacetylase), poxB
      (pyruvate oxidase) double mutant (ML112)) and a fadD, ack-pta, poxB triple mutant
      (ML115). The engineered E. coli cells expressing acyl-ACP thioesterase with
      glucose yield is higher than 40% of theoretical yield. Compared to MG1655(pXZ18)
      and ML103(pXZ18), acetate forming pathway deletion strains such as ML112(pXZ18)
      and ML115(pXZ18) produced similar quantity of total free fatty acids, which
      indicated that acetyl-CoA availability does not appear to be limiting factor for
      fatty acid production in these strains. However, these strains did show
      significant differences in the composition of free fatty acids. Different from
      MG1655(pXZ18) and ML103(pXZ18), acetate formation pathway deletion strains such
      as ML112(pXZ18) and ML115(pXZ18) produced similar level of C14, C16:1 and C16
      free fatty acids, and the free fatty acid compositions of both strains did not
      change significantly with time. In addition, the strains bearing the fadD
      mutation showed significant differences in the quantities of free fatty acids
      found in the broth. Finally, we examined two potential screening methods for
      selecting and isolating high free fatty acids producing cells.

PMID- 22480946
TI  - Epidemiological and clinical features of an older high-risk population of
      skateboarders.
AB  - BACKGROUND: Skateboard injuries have been described in the media and scientific
      journals as a problem prevalent among children and adolescents. Skateboarding
      popularity has continued to grow since the 1970s with ridership increasing to
      include all age groups. Recently, surgeons at one trauma centre at an urban
      hospital noted an increase in the number of older skateboarders with life
      threatening injuries. We hypothesise that the clinical and epidemiological
      features of skateboard-related injuries from one trauma centre (TC) will be
      different from injured skateboarders identified in the U.S. National Trauma Data
      Bank (NTDB). We also sought to identify factors related to poor outcomes in the
      TC and NTDB patient groups. METHODS: Two injured skateboarder patient groups were
      identified and compared using proportional morbidity odds ratios (PMORs) and
      multivariable methods to estimate differences among factors common to both groups
      of patients. Clinical and demographic features were evaluated for hospital
      admitted patients injured whilst riding a skateboard. Chi-square tests, PMORs and
      logistic regression were used to determine outcome differences between patients
      in both groups. RESULTS: Patients in the TC group were on average older, with
      higher Injury Severity Scores (ISS), more head injuries requiring neurosurgical
      intervention, longer ICU and hospital stays, and injured more frequently on local
      streets than patients in the NTDB series. Poor outcomes in the TC group were
      related to moderate or severe head injuries and presence of a head/face injury.
      For NTDB patients, a GCS of <13, a head/face injury and an ISS of 25+ were
      related to poor outcomes. CONCLUSIONS: From our Trauma Centre we describe an
      older injured skateboarding population, clinically and epidemiologically
      different from injured patients identified in the NTDB as well as those described
      in the literature. The greater severity of injury, including traumatic brain
      injury, has direct implications for preventive and educational measures and the
      planning of emergency surgical response.

PMID- 22480947
TI  - Enhancement of bone regeneration through facile surface functionalization of
      solid freeform fabrication-based three-dimensional scaffolds using mussel
      adhesive proteins.
AB  - Solid freeform fabrication (SFF) is recognized as a promising tool for creating
      tissue engineering scaffolds due to advantages such as superior interconnectivity
      and highly porous structure. Despite structural support for SFF-based three
      dimensional (3-D) scaffolds that can lead to tissue regeneration, lack of cell
      recognition motifs and/or biochemical factors has been considered a limitation.
      Previously, recombinant mussel adhesive proteins (MAPs) were successfully
      demonstrated to be functional cell adhesion materials on various surfaces due to
      their peculiar adhesive properties. Herein, MAPs were applied as surface
      functionalization materials to SFF-based 3-D polycaprolactone/poly(lactic-co
      glycolic acid) scaffolds. We successfully coated MAPs onto scaffold surfaces by
      simply dipping the scaffolds into the MAP solution, which was confirmed through X
      ray photoelectron spectroscopy and scanning electron microscopy analyses. Through
      in vitro study using human adipose tissue-derived stem cells (hADSCs),
      significant enhancement of cellular activities such as attachment, proliferation,
      and osteogenic differentiation was observed on MAP-coated 3-D scaffolds,
      especially on which fused arginine-glycine-aspartic acid peptides were
      efficiently exposed. In addition, we found that in vivo hADSC implantation with
      MAP-coated scaffolds enhanced bone regeneration in a rat calvarial defect model.
      These results collectively demonstrate that facile surface functionalization of 3
      D scaffolds using MAP would be a promising strategy for successful tissue
      engineering applications.

PMID- 22480948
TI  - Iminoheterocycle as a druggable motif: BACE1 inhibitors and beyond.
AB  - Beta-secretase 1 (BACE1) is a central nervous system (CNS) aspartyl protease
      required for production of amyloid beta (Abeta) peptides. Brain-penetrant BACE1
      inhibitors are central to test the 'amyloid hypothesis', which suggests that a
      reduction of Abeta species in the CNS would halt or even reverse Alzheimer's
      disease. Discovery of the iminoheterocycle class of BACE1 inhibitors (which show
      robust efficacy in reduction of CNS Abeta species in animal models) marked an
      important milestone. These discoveries arose independently from multiple research
      laboratories that took different paths to end at the same scaffolds. These
      druggable motifs should be applicable to other aspartyl proteases of therapeutic
      importance and also to other protein targets involving crucial interactions with
      carboxylic acid side chains. Here, a comparison of these approaches to BACE1
      discovery will showcase how it is important to pay attention to the intrinsic
      physicochemical properties of the lead series, even at the very early stage of
      drug discovery.

PMID- 22480949
TI  - Ready for a paradigm shift? Part 2: introducing qualitative research
      methodologies and methods.
AB  - This paper explores a number of commonly used methodologies and methods in
      qualitative research, namely grounded theory, case study, phenomenology,
      ethnography and narrative research. For each methodology a brief history of its
      development and variants is given, followed by typical methods of data collection
      and analysis. Examples of manual therapy qualitative research studies are
      highlighted for each methodology. Data collection methods are then discussed and
      include individual interviews, focus groups, observation and documentary
      analysis. A frequently used method of data analysis, thematic analysis, is
      briefly explained. Finally, the strategies to enhance the quality of qualitative
      research is explored and compared to those of quantitative research.

PMID- 22480950
TI  - Ready for a paradigm shift? Part 1: introducing the philosophy of qualitative
      research.
AB  - The manual therapy professions have almost exclusively focused on the use of
      quantitative research to help inform their practices. This paper argues that a
      greater use of qualitative research will help develop a more robust and
      comprehensive knowledge base in manual therapy. The types of knowledge used in
      practice and generated from the two research paradigms are explored. It is hoped
      that an understanding of the philosophical and theoretical underpinnings of
      qualitative research may encourage more manual therapists to value and use this
      approach to help further inform their practice; for some, this may involve a
      paradigm shift in thinking.

PMID- 22480951
TI  - Levels of YKL-40 in pleural effusions and blood from patients with pulmonary or
      pleural disease.
AB  - BACKGROUND: YKL-40 (a chitinase-like protein) is an inflammatory biomarker that
      is associated with lung injury pathogenesis. We aimed to identify the diagnostic
      values of YKL-40 in pleural effusions and to evaluate circulating YKL-40 levels
      during multiple etiological pulmonary/pleural diseases and the role of YKL-40 as
      a monitoring marker of inflammatory pulmonary disease. METHODS: Pleural YKL-40
      (n=197), YKL-39 (the most homologous chitinase-like protein to human YKL-40), and
      conventional pleural marker levels were measured in patients with
      pulmonary/pleural disease. Additionally, serum YKL-40 and YKL-39 levels were
      analyzed in both patients and controls (n=432) and serially monitored in patients
      with asthma (n=27) or pneumonia (n=22). RESULTS: Pleural YKL-40 levels were
      higher than those in the serum and highest in tuberculous pleural effusions
      (TPEs; 1181 ng/mL), followed by parapneumonic, malignant, and cardiogenic
      effusions (560 ng/mL). The diagnostic accuracy of pleural YKL-40 (0.78) for
      discriminating between tuberculous and malignant effusion was comparable to or
      greater than those of YKL-39, total protein, C-reactive protein and CYFRA 21-1,
      and lower than those of adenosine deaminase (p<0.05) and carcinoembriogenic
      antigen (p=0.05). Serum YKL-40 levels were higher in the pneumonia group than in
      the cancer, asthma, or control groups. Following treatment, serum YKL-40 levels
      were more greatly reduced in pneumonia patients than in asthma patients. Serum
      YKL-39 levels did not differ between patients and controls. CONCLUSIONS: Pleural
      YKL-40 levels are elevated in TPEs and have fairly good diagnostic efficacy for
      detecting TPEs. However, adenosine deaminase is more efficient for detecting TPEs
      than pleural YKL-40. Serum YKL-40 levels are highest during pneumonia compared to
      common pulmonary/pleural diseases and are more useful for monitoring pneumonia
      than asthma.

PMID- 22480952
TI  - Complexity of RNA polymerase II elongation dynamics.
AB  - Transcription of protein-coding genes by RNA polymerase II can be regulated at
      multiple points during the process of RNA synthesis, including initiation,
      elongation, and termination. In vivo data suggests that elongating polymerases
      exhibit heterogeneity throughout the gene body, suggestive of changes in
      elongation rate and/or pausing. Here, we review evidence from a variety of
      different experimental approaches for understanding regulation of transcription
      elongation. We compare steady-state measurements of nascent RNA density and
      polymerase occupancy to time-resolved measurements and point out areas of
      disagreement. Finally, we discuss future avenues of investigation for
      understanding this critically important step in gene regulation. This article is
      part of a Special Issue entitled: Chromatin in time and space.

PMID- 22480953
TI  - Regulation of mammalian mitochondrial translation by post-translational
      modifications.
AB  - Mitochondria are responsible for the production of over 90% of the energy in
      eukaryotes through oxidative phosphorylation performed by electron transfer and
      ATP synthase complexes. Mitochondrial translation machinery is responsible for
      the synthesis of 13 essential proteins of these complexes encoded by the
      mitochondrial genome. Emerging data suggest that acetyl-CoA, NAD(+), and ATP are
      involved in regulation of this machinery through post-translational modifications
      of its protein components. Recent high-throughput proteomics analyses and mapping
      studies have provided further evidence for phosphorylation and acetylation of
      ribosomal proteins and translation factors. Here, we will review our current
      knowledge related to these modifications and their possible role(s) in the
      regulation of mitochondrial protein synthesis using the homology between
      mitochondrial and bacterial translation machineries. However, we have yet to
      determine the effects of phosphorylation and acetylation of translation
      components in mammalian mitochondrial biogenesis. This article is part of a
      Special Issue entitled: Mitochondrial Gene Expression.

PMID- 22480954
TI  - Who should be really considered as a poor mobilizer in the plerixafor era?
AB  - Patients with a number of peripheral CD34+ cells >=20/MUL have recently been
      defined in the literature as "poor mobilizers". We retrospectively reviewed
      medical records from a total of 248 patients affected by hematological
      malignancies or solid tumors undergoing peripheral blood stem cell collection
      following chemotherapy plus G-CSF. On the basis of the CD34+ cell peak in
      peripheral blood following mobilization therapy, patients were defined as good
      mobilizers (group A, CD34+ cells >=20/MUL), relative poor mobilizers (group B,
      CD34+ cells <20 and >=8/MUL) and absolute poor mobilizers (group C, CD34+ cells
      <8/MUL). One hundred and seventy-seven (71%) patients resulted good mobilizers,
      35 (14%) patients relative poor mobilizers and 36 (15%) patients absolute poor
      mobilizers. Target of stem cell collection was >=2.0*10(6) CD34+cells/kg for each
      transplantation procedure. All patients in group A, 20 patients in group B (57%)
      and 1 patient in group C (2.7%) were able to collect >=2.0*10(6) CD34+cells/kg.
      The multivariate analysis confirmed that more than three lines of previous
      chemotherapy and a previous autologous PBSC transplantation negatively affect
      mobilization of CD34+ cells in peripheral blood. Our data suggest that a number
      of CD34+ cells >=20/MUL does not always result in a failed stem cell collection
      and in fact in our patient series more than 70% of the patients defined as poor
      mobilizers have indeed collected the minimum number of 2.0*10(6) CD34+cells/kg
      required for a successful transplantation. The use of new agent such as CXCR4
      antagonist plerixafor might further improve mobilization efficacy in such
      patients.

PMID- 22480955
TI  - Maintenance of surface antigens and the absence of an apoptotic marker are
      observed during storage of granulocyte concentrates collected by bag separation
      method.
AB  - Granulocytes were collected by the bag separation method and stored in whole
      blood for up to 72h. We evaluated the expressions of various surface antigens:
      CD62L, CD11b, CD18, CD64, CD16b, and CD95. Apoptosis was assessed both by flow
      cytometry and by light microscopy. Expression levels of all the surface antigens
      were shown to be maintained during storage for up to 72h. Approximately 80% of
      granulocytes were annexin V negative until 72h after collection. The storage of
      granulocyte concentrates collected by the bag separation method may maintain
      granulocyte surface antigens and lack an apoptotic marker.

PMID- 22480956
TI  - Leukapheresis in management hyperleucocytosis induced complications in two
      pediatric patients with chronic myelogenous leukemia.
AB  - Complications caused by elevated white blood cell count in pediatric patients
      with CML could be a presenting feature of the disease. Here, we present two
      adolescents, aged 16 and 17years, who were admitted for investigation of
      extremely elevated leukocytes and complications of leucostasis. Initial
      manifestations were priapism and blurred vision, respectively. Diagnosis of
      chronic phase of chronic myeloid leukemia is established, and conventional
      measures for leucoreduction began. However, since there were no improvements, a
      leukapheresis procedure was initiated. After undergoing 3 daily procedures the
      leukocyte count declined for each patient, with resolution of pripaism and
      ophtalmological disturbances. Leukapheresis is safe and effective therapeutic
      option for patients with complications of hyperleucocytosis. If started in a
      timely manner, permanent organ damage or death could be avoided.

PMID- 22480957
TI  - Hippocampal novelty activations in schizophrenia: disease and medication effects.
AB  - We examined hippocampal activation in schizophrenia (SZ) with fMRI BOLD in
      response to the presentation of novel and familiar scenes. Voxel-wise analysis
      showed no group differences. However, anatomical region-of-interest analyses
      contrasting normal (NL), SZ-on-medication (SZ-ON), SZ-off-medication (SZ-OFF)
      showed substantial differences in MTL-based novelty responding, accounted for by
      the reduction in novelty responses in the SZ-OFF predominantly in the anterior
      hippocampus and parahippocampal cortex. These differences in novelty-based
      activation in the SZ-OFF group represent disease characteristics of schizophrenia
      without confounding effects of antipsychotic medication and illustrate the
      tendency of antipsychotic drug treatment to improve memory functions in
      schizophrenia.

PMID- 22480959
TI  - How to write a critically appraised topic (CAT).
AB  - Medical knowledge and the volume of scientific articles published have expanded
      rapidly over the past 50 years. Evidence-based practice (EBP) has developed to
      help health practitioners get more benefit from the increasing volume of
      information to solve complex health problems. A format for sharing information in
      EBP is the critically appraised topic (CAT). A CAT is a standardized summary of
      research evidence organized around a clinical question, aimed at providing both a
      critique of the research and a statement of the clinical relevance of results. In
      this review, we explain the five steps involved in writing a CAT for a clinical
      purpose ("Ask," "Search," "Appraise," "Apply," and "Evaluate") and introduce some
      of the useful electronic resources available to help in creating CATs.

PMID- 22480958
TI  - Neurobiology of self-awareness in schizophrenia: an fMRI study.
AB  - Self-awareness (SA) is one of the core domains of higher cortical functions and
      is frequently compromised in schizophrenia. Deficits in SA have been associated
      with functional and psychosocial impairment in this patient population. However,
      despite its clinical significance, only a few studies have examined the neural
      substrates of self-referential processing in schizophrenia. The aim of this study
      was to assess self-awareness in schizophrenia using a functional magnetic
      resonance imaging (fMRI) paradigm designed to elicit judgments of self-reference
      in a simulated social context. While scanned, volunteers looked at visually
      displayed sentences that had the volunteer's own first name (self-directed
      sentence-stimulus) or an unknown other person's first name (other-directed
      sentence stimulus) as the grammatical subject of the sentence. The volunteers
      were asked to discern whether each sentence-stimulus was about the volunteer
      personally (during a self-referential cue epoch) or asked whether each statement
      was about someone else (during an other-referential cue epoch). We predicted that
      individuals with schizophrenia would demonstrate altered functional activation to
      self- and other-directed sentence-stimuli as compared to controls. Fifteen
      controls and seventeen schizophrenia volunteers completed clinical assessments
      and SA fMRI task on a 3T Philips 3.0 T Achieva system. The results showed
      significantly greater activation in schizophrenia compared to controls for
      cortical midline structures in response to self- vs. other-directed sentence
      stimuli. These findings support results from earlier studies and demonstrate
      selective alteration in the activation of cortical midline structures associated
      with evaluations of self-reference in schizophrenia as compared to controls.

PMID- 22480960
TI  - Quality of communication: different patterns of reporting the location of the tip
      of a nasogastric tube.
AB  - PURPOSE: This investigation is part of a prospective National Institutes of
      Health-funded study evaluating three different methods for estimating the optimal
      length for placement of a new nasogastric (NG) tube. Abdomen radiographs were
      required to determine the location of the tube tip. Our objective was to analyze
      different methods by which the tube location was described in the radiology
      report of the abdominal radiographs, and the influence of the presence or absence
      of a relevant clinical history. METHODS: We reviewed the imaging reports obtained
      following placement of a new nasogastric tube in patients enrolled in the study.
      RESULTS: There were 188 studies. The x-ray report contained separate description
      and impression sections in 154. In 24 they were combined. When the history on the
      requisition indicated "tube placement" as the reason for the study, the location
      of the tube tip was given in the impression on 134/141 (95%). When the
      requisition failed to mention "tube placement" as the study indication, the
      impression only mentioned the tube tip location 4/13 (31%). The report provided a
      specific location for the tube tip in 115 of the 188 cases; in 73 of the 188
      cases, the report stated that the tube tip "overlies/is in the region of" the
      stomach. On 29 occasions the report stated that the tube, not the tube tip, was
      in the stomach. CONCLUSIONS: There is variation in the manner of reporting the
      location of NG tube tips. When the requisition fails to indicate "tube placement"
      as the study indication, the report impression often fails to mention the tube
      location.

PMID- 22480961
TI  - Research imaging in an academic medical center.
AB  - RATIONALE AND OBJECTIVES: Managing and supervising the complex imaging
      examinations performed for clinical research in an academic medical center can be
      a daunting task. Coordinating with both radiology and research staff to ensure
      that the necessary imaging is performed, analyzed, and delivered in accordance
      with the research protocol is nontrivial. The purpose of this communication is to
      report on the establishment of a new Human Imaging Research Office (HIRO) at our
      institution that provides a dedicated infrastructure to assist with these issues
      and improve collaborations between radiology and research staff. MATERIALS AND
      METHODS: The HIRO was created with three primary responsibilities: 1) coordinate
      the acquisition of images for clinical research per the study protocol, 2)
      facilitate reliable and consistent assessment of disease response for clinical
      research, and 3) manage and distribute clinical research images in a compliant
      manner. RESULTS: The HIRO currently provides assistance for 191 clinical research
      studies from 14 sections and departments within our medical center and performs
      quality assessment of image-based measurements for six clinical research studies.
      The HIRO has fulfilled 1806 requests for medical images, delivering 81,712
      imaging examinations (more than 44.1 million images) and related reports to
      investigators for research purposes. CONCLUSIONS: The ultimate goal of the HIRO
      is to increase the level of satisfaction and interaction among investigators,
      research subjects, radiologists, and other imaging professionals. Clinical
      research studies that use the HIRO benefit from a more efficient and accurate
      imaging process. The HIRO model could be adopted by other academic medical
      centers to support their clinical research activities; the details of
      implementation may differ among institutions, but the need to support imaging in
      clinical research through a dedicated, centralized initiative should apply to
      most academic medical centers.

PMID- 22480962
TI  - The use of the lower limit of normal as a criterion for COPD excludes patients
      with increased morbidity and high consumption of health-care resources.
AB  - The objective of this study is to analyze the clinical characteristics of two
      COPD patient populations: one diagnosed using the lower limit of normal (LLN) and
      another diagnosed by the GOLD criteria. We also compared the population excluded
      by the LLN criterion with a non-COPD control population. The COPD patients
      determined with the LLN criterion presented significantly lower levels of
      FEV1/FVC at 0.55 (0.8) vs. 0.66 (0.2), P=.000; FEV1 44.9% (14) vs. 53.8% (13),
      P=.000, and FVC 64.7% (17) vs. 70.4% p 0.04. The two COPD groups presented more
      frequent ER visits in the last year (57% and 52% of the patients, respectively,
      compared with 11.9% of the control group), without any statistically significant
      differences between the two. This same pattern was observed in the number of ER
      visits in the last year: 1.98 (1.6), 1.84 (1.5) and 1.18 (0.7), respectively.
      When we analyzed the prevalence of the comorbidities that are most frequently
      associated COPD, there was a clear increase in the percentage of patients who
      presented associated disorders compared with the control group. Nevertheless,
      these differences were not very relevant between the two COPD groups. The
      differences also were not relevant between both COPD groups in the
      pharmacological prescription profile. In conclusion, the use of the LLN as a
      criterion for establishing the diagnosis of COPD, compared with the GOLD
      criteria, excludes a population with important clinical manifestations and with a
      high consumption of health-care resources. Before its implementation, the
      relevance of applying this criterion in clinical practice should be analyzed.

PMID- 22480963
TI  - Generic antibiotic drugs: is effectiveness guaranteed?
AB  - There are recently published arguments suggesting all generic antibiotic drugs do
      not present the full reliability needed to claim therapeutic equivalence with
      branded drugs. The problem is especially crucial for generic intravenous drugs,
      which do not need any bioequivalence study before they can be marketed. The
      evaluation of generic antibiotic drug effectiveness yields an important
      dispersion of results according to antibiotic agents and for the same antibiotic
      agent all generic drugs are not equivalent. There are differences at all levels:
      drug components, levels of impurity, pharmacokinetics,
      pharmacokinetic/pharmacodynamic relationship, in vitro effectiveness, therapeutic
      effectiveness in experimental models, etc. So that finally, the specifications
      approved in the initial submission file of a brand name drugs are not always
      respected by a generic drug. There is also a specific problem of taste and
      treatment acceptability for pediatric oral antibiotic drugs. Available data on
      clinical effectiveness is excessively rare. The marketing of a great number of
      generic drugs of the same specialty is followed by a sometimes very important
      increase of their use, even in countries where consumption is low. The corollary
      of this increase in consumption is an increase of resistance, and this is
      especially true for oral fluoroquinolones. Even if most of this information needs
      to be verified, it seems necessary to review regulations for marketing
      authorization of generic antibiotic drugs.

PMID- 22480964
TI  - WITHDRAWN: Updates for the antibiotic treatment of legionellosis in adults.
AB  - Cet article a du etre retire conformement a la ligne de conduite d'Elsevier
      concernant le retrait d'articles. Vous pouvez consulter le site
      (http://www.elsevier.com/locate/withdrawalpolicy) pour de plus amples
      renseignements. L'editeur vous prie d'accepter ses excuses pour ce desagrement.

PMID- 22480965
TI  - Economic impact of healthcare resource utilisation patterns among patients
      diagnosed with advanced melanoma in the United Kingdom, Italy, and France:
      results from a retrospective, longitudinal survey (MELODY study).
AB  - OBJECTIVE: To describe patterns of healthcare resource utilisation and associated
      costs for patients with advanced melanoma in the United Kingdom (UK), Italy, and
      France. METHODS: For patients receiving systemic treatment, or supportive care,
      data describing hospitalisations, hospice care, and outpatient visits were
      retrieved retrospectively from advanced disease diagnosis as part of a
      multicountry observational study. Costs were estimated by multiplying utilisation
      level by unit cost. In an exploratory analysis, costs were compared between
      individuals who died within one year of initiating first-line treatment (short
      term survivors) and those with >= 1 year follow-up (long-term survivors).
      RESULTS: Hospitalisation costs were highest in France (?6262 per-person compared
      with ?3225 in the UK and ?2486 in Italy), reflecting higher rates of
      hospitalisation. In contrast, outpatient costs were highest in the UK (?782 per
      person, compared with ?115 in France and ?72 in Italy), reflecting the highest
      rate and frequency of outpatient visits and the highest cost per visit.
      Hospitalisation rates were consistently higher during supportive care compared
      with systemic therapy. Roughly one-third of patients entered clinical trials and
      were not included in the analysis. In exploratory analysis, total costs were
      generally higher for long-term survivors, but monthly per-patient costs were
      generally lower for long-term survivors, consistent with a hypothesis that
      resource utilisation and costs do not necessarily increase proportionally with
      extended survival. CONCLUSION: Total costs associated with resource utilisation
      for advanced melanoma patients varied across countries. Overall cost differences
      were due to differences in frequency and intensity of utilisation patterns and
      variation in unit costs of health resources.

PMID- 22480966
TI  - Safety evaluation of a high lipid Whole Algalin Flour (WAF) from Chlorella
      protothecoides.
AB  - Microalgae such as Chlorella spp. have a long history of use in human food. A
      high lipid Whole Algalin Flour (WAF) composed of dried milled Chlorella
      protothecoides was evaluated for subchronic toxicity and genotoxic potential.
      Likelihood of food allergy potential was also evaluated by human repeat-insult
      patch test. In the subchronic study, rats were fed dietary levels of 25,000,
      50,000 or 100,000 ppm WAF in feed for 93-94 days. No mortalities occurred. No
      treatment-related effects were identified for general condition, body weight,
      food consumption, ophthalmology, urinalysis, hematology, clinical chemistry,
      gross pathology, organ weights, and histopathology. Although statistically
      significant effects were noted for several endpoints, none was test-substance
      related. The no-observed-adverse-effect level (NOAEL) for WAF was based on
      consumption of the 100,000 ppm diet, the highest dietary concentration tested,
      and was 4807 mg/kg bw/d in male rats and 5366 mg/kg bw/d in female rats.
      Additionally, WAF (<= 5000 MUg/plate) was not mutagenic in Salmonella typhimurium
      or Escherichia coli tester strains nor did WAF induce a clastogenic response in
      bone marrow from mice given a single oral dose (2000 mg/kg bw). Further, WAF did
      not elicit skin sensitization in a repeat-insult dermal patch test which
      indicates little potential for food allergy.

PMID- 22480967
TI  - Parathyroid carcinoma: a difficult histological diagnosis.
AB  - INTRODUCTION: Parathyroid carcinomas are rare and usually difficult to diagnose,
      both clinically and histologically. CASE REPORT: A 60-year-old man was
      hospitalised for hypotension. Investigations revealed renal failure associated
      with hypercalcaemia and elevated serum parathormone. (99m)Tc-sestamibi
      scintigraphy of the parathyroid glands (PT) revealed a mass in the right PT that
      was treated by parathyroidectomy and recurrent laryngeal lymph node dissection.
      Histological examination demonstrated a tumour with numerous cytonuclear atypias
      and immuno-histochemistry demonstrated PTH expression by tumour cells without
      loss of parafibromin expression. The diagnosis of PTC was based on criteria of
      invasion and local aggressiveness, despite the absence of lymph node metastasis.
      The patient developed four recurrences, treated surgically and by adjuvant
      radiotherapy. DISCUSSION: The diagnosis of PTC is usually difficult to establish
      on a simple histological examination in the absence of specific cytological,
      architectural or immuno-histochemical markers. This diagnosis must therefore be
      based on a combination of clinical, radiological and histological signs in a
      context of atypical presentation of parathyroid tumour.

PMID- 22480968
TI  - Comment to "Unusual evolution of ciprofloxacin-induced hepatitis revealing a
      possible link with IgG4-associated autoimmune hepatitis".

PMID- 22480969
TI  - Simplified identification of Lynch syndrome: a prospective, multicenter study.
AB  - BACKGROUND: Recommended strategies to screen for Lynch syndrome in colorectal
      cancer are not applied in daily practice and most of Lynch cases remain
      undiagnosed. AIMS: We investigated in routine conditions a strategy that uses
      simplified clinical criteria plus detection of MisMatch Repair deficiency in
      tumours to identify Lynch carriers. METHODS: Colorectal cancer patients that met
      at least one of three clinical criteria were included: (1) colorectal cancer
      before 50 years, (2) personal history of colorectal or endometrial cancer, (3)
      first-degree relative history of colorectal or endometrial cancer. All tumours
      underwent an MisMatch Repair test combining microsatellite instability analysis
      and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair
      deficient tumour were offered germline testing. RESULTS: Of the 307 patients
      fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient
      tumour. Amongst them 27 were identified as Lynch carriers (20 with germline
      mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of
      genetic testing). The simplified clinical criteria selected a population whose
      MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome.
      CONCLUSION: This bio-clinical strategy based on simplified clinical criteria
      combined with an MisMatch Repair test efficiently detected LS cases and is easy
      to use in clinical practice, outside expert centres.

PMID- 22480970
TI  - Stevens-Johnson syndrome after treatment with bendamustine.

PMID- 22480971
TI  - Hypersensitivity to alkylation treatment of primary fibroblasts from patients
      with therapy-related myeloid neoplasms.

PMID- 22480972
TI  - Cervical auricles in a family.

PMID- 22480973
TI  - Analysis of HilC/D-dependent invF promoter expression under different culture
      conditions.
AB  - In Salmonella enterica serovar Typhimurium, many of the genes required for
      intestinal penetration and invasion of host cells are encoded within the
      Salmonella pathogenicity island 1 (SPI1). The expression of invF, which is a
      positive transcriptional activator of SPI1, is controlled by HilA-dependent (invF
      1) and HilC/D-dependent (invF-2) promoters. Transcriptional analysis of invF
      revealed that the invF-2 promoter (P(invF-2)) was not activated when cells were
      grown in standing culture conditions (which are known to induce SPI1) and that
      hilD mutation decreased the expression of P(invF-2) only in shaking culture
      conditions. In the absence of invF-1 promoter (P(invF-1)), P(invF-2) promoted
      InvF production and sipC expression (which is regulated by InvF) in shaking
      culture conditions. An analysis of the transcription patterns of plasmids
      harboring the lacZY reporter gene under various P(invF-2) derivatives with
      truncations or mutations revealed that the downstream region of the P(invF-2)
      transcription start site (i.e., +148 to +363) plays a role in repressing P(invF
      2) in standing culture and in HilD-dependent activation of P(invF-2) in shaking
      culture conditions. The expression of invH overlaps with P(invF-2), but they are
      transcribed in opposite directions. However, invH expression did not influence
      P(invF-2) activity. This suggests that independent regulation of the two invF
      promoters allows Salmonella to respond quickly to environmental changes.

PMID- 22480974
TI  - [Erythema ab igne caused by laptop computer use].

PMID- 22480976
TI  - Anatomic hemispherectomy: historical perspective.
AB  - The history of surgical treatment for hemispheric epilepsy is rich with colorful
      twists and turns. The authors trace the evolution of the surgical treatment of
      hemispheric epilepsy from radical anatomic resections to current less invasive
      disconnection procedures. Anatomic hemispherectomy (AH) was first described by
      Dandy in 1928 as a treatment for gliomas. The first report of this technique to
      control seizures was by McKenzie in 1938. AH gained wide popularity but began to
      fall out of favor after the description of superficial cerebral hemosiderosis in
      1966. To reduce the morbidity and mortality associated with AH, Rasmussen
      introduced functional hemispherectomy in 1974. The technique of hemispherotomy
      was introduced in the 1990 s to minimize the extent of brain removal while
      maximizing the white matter disconnections. Thus, surgery for hemispheric
      epilepsy has undergone dramatic transformation since the technique was first
      introduced. Less invasive techniques have been developed to reduce surgical
      morbidity. Although optimal seizure control is best achieved with radical AH, the
      newer less invasive disconnection techniques appear to achieve near-comparable
      postoperative seizure control with a significantly lower rate of complications.

PMID- 22480977
TI  - Pituitary metastases: role of surgery.
AB  - OBJECTIVE: To evaluate the clinical and radiographic manifestations of pituitary
      metastases (PM), discuss the role of surgery, and briefly review the pertinent
      literature. METHODS: At a single institution between January 1992 and July 2011,
      15 patients with PM were surgically treated (all cases were confirmed by
      histologic analysis). Of patients, 14 complained of visual impairment, 8
      complained of headache, 4 complained of ophthalmoplegia, and 11 complained of
      endocrine disturbances manifesting as diabetes insipidus (7 patients) and
      anterior hypopituitarism (4 patients). RESULTS: After transsphenoidal surgery,
      visual disturbances improved in 12 cases, headache improved in 5 cases, and
      ophthalmoplegia improved in 2 cases. Endocrinologic function remained unchanged
      in all cases. The mean survival time was 11.8 months (range, 3-43 months); one
      patient still survives after 33 months. CONCLUSIONS: The study cohort includes
      patients representing two clinical situations: (i) patients with a preoperative
      suspicion of PM and (ii) patients in whom the metastasis was an unexpected
      finding during surgery performed for a presumed pituitary adenoma. The former
      situation is indicative of the possibilities and limits of surgery, which may
      confirm the diagnosis but is only palliative, improving quality of life without
      improving life expectancy. The latter situation reveals how misleading clinical
      and radiographic features of PM can be. Considering these results, surgical
      treatment of PM should be specifically decided based on patient performance
      status, tumor staging, and patient preference.

PMID- 22480975
TI  - Diverse types of ganglion cell photoreceptors in the mammalian retina.
AB  - Photoreceptors carry out the first step in vision by capturing light and
      transducing it into electrical signals. Rod and cone photoreceptors efficiently
      translate photon capture into electrical signals by light activation of opsin
      type photopigments. Until recently, the central dogma was that, for mammals, all
      phototransduction occurred in rods and cones. However, the recent discovery of a
      novel photoreceptor type in the inner retina has fundamentally challenged this
      view. These retinal ganglion cells are intrinsically photosensitive and mediate a
      broad range of physiological responses such as photoentrainment of the circadian
      clock, light regulation of sleep, pupillary light reflex, and light suppression
      of melatonin secretion. Intrinsically photosensitive retinal ganglion cells
      express melanopsin, a novel opsin-based signaling mechanism reminiscent of that
      found in invertebrate rhabdomeric photoreceptors. Melanopsin-expressing retinal
      ganglion cells convey environmental irradiance information directly to brain
      centers such as the hypothalamus, preoptic nucleus, and lateral geniculate
      nucleus. Initial studies suggested that these melanopsin-expressing
      photoreceptors were an anatomically and functionally homogeneous population.
      However, over the past decade or so, it has become apparent that these
      photoreceptors are distinguishable as individual subtypes on the basis of their
      morphology, molecular markers, functional properties, and efferent projections.
      These results have provided a novel classification scheme with five melanopsin
      photoreceptor subtypes in the mammalian retina, each presumably with differential
      input and output properties. In this review, we summarize the evidence for the
      structural and functional diversity of melanopsin photoreceptor subtypes and
      current controversies in the field.

PMID- 22480978
TI  - Incidence and treatment of central nervous system tumors in Suriname.
AB  - OBJECTIVE: To estimate the incidence of central nervous system (CNS) tumors in
      Suriname. METHODS: A retrospective chart review was performed at the Academic
      Hospital Paramaribo and the State Health Insurance foundation. Patients receiving
      a diagnosis of CNS tumor in the period 2000-2010 were included in the study if a
      computed tomography scan or magnetic resonance imaging study was available.
      Demographic data and patient characteristics and disease variables were
      retrieved. RESULTS: The study comprised 251 patients who met the inclusion
      criteria. The incidence of treated CNS tumors was 5 per 100,000 per year. There
      was a peak incidence in the 41-50 age group and a male-to-female ratio of 1:1.46.
      Of CNS tumors, 21% were gliomas, 26.7% were meningiomas, 4.7% were schwannomas,
      and 12.0% were pituitary adenomas. Suriname has a low glioma incidence compared
      with globally (40%-60% of CNS tumors globally). The incidence of pituitary
      adenoma was higher than expected. There are indications for a higher glioma and
      meningioma incidence in Javanese and a higher metastases incidence in Creoles.
      CONCLUSIONS: The annual incidence of treated CNS tumors of 5 per 100,000
      inhabitants in Suriname was in accordance with the expectation of an incidence of
      3-6 per 100,000. Suriname is considered a country with a low cancer incidence.
      The differences found among various subgroups were too small to make definitive
      statements.

PMID- 22480979
TI  - A survey-based study of wrong-level lumbar spine surgery: the scope of the
      problem and current practices in place to help avoid these errors.
AB  - OBJECTIVE: To understand better the scope of wrong-level lumbar spine surgery and
      current practices in place to help avoid such errors. METHODS: The Joint Section
      on Disorders of the Spine and Peripheral Nerves (Spine Section) developed a
      survey on single-level lumbar spine decompression surgery. Invitations to
      complete the Web-based survey were sent to all Spine Section members. Respondents
      were assured of confidentiality. RESULTS: There were 569 responses from 1045
      requests (54%). Most surgeons either routinely (74%) or sometimes (11%) obtain
      preoperative imaging for incision planning. Most surgeons indicated that they
      obtained imaging after the incision was performed for localization either
      routinely before bone removal (73%) or most frequently before bone removal but
      occasionally after (16%). Almost 50% of reporting surgeons have performed wrong
      level lumbar spine surgery at least once, and >10% have performed wrong-side
      lumbar spine surgery at least once. Nearly 20% of responding surgeons have been
      the subject of at least one malpractice case relating to these errors. Only 40%
      of respondents believed that the site marking/"time out" protocol of The Joint
      Commission on the Accreditation of Healthcare Organizations has led to a
      reduction in these errors. CONCLUSIONS: There is substantial heterogeneity in
      approaches used to localize operative levels in the lumbar spine. Existing safety
      protocols may not be mitigating wrong-level surgery to the extent previously
      thought.

PMID- 22480980
TI  - Percutaneous retrogasserian balloon compression for trigeminal neuralgia: review
      of critical technical details and outcomes.
AB  - OBJECTIVE: To describe percutaneous balloon compression (PBC) of the trigeminal
      rootlets as treatment for trigeminal neuralgia (TN), including history, operative
      techniques, outcomes, side effects, and some recent findings increasing the
      likelihood of a positive outcome. METHODS: PBC is indicated in patients with TN
      in whom microvascular decompression is considered less suitable. The procedure is
      simplified by the use of biplanar fluoroscopy, although it is usually carried out
      with C-arm fluoroscopy to facilitate the introduction of the needle and the
      visualization of the inflated catheter. In the right position, a clearly defined
      pear shape usually appears after injection of 0.5-0.7 mL of contrast material.
      The balloon is kept inflated for 1.5-3 minutes. It is crucial to obtain a pear
      shape because this probably is the most significant factor for obtaining good,
      long-lasting pain relief. RESULTS: An analysis of 100 consecutive PBC procedures
      showed an initial success rate of 90% and a median pain-free time without
      medication of 28 months. Subdividing these patients into primary TN (n = 77) and
      TN secondary to multiple sclerosis (n = 23), the median pain-free times were 33
      months and 24 months (P = 0.2), indicating that the outcome may depend on the
      preoperative conditions. CONCLUSIONS: Complications and side effects include
      cardiovascular stress during the procedure, local hemorrhages in the cheek,
      postoperative sensory disturbance, masseter weakness, infections, and transitory
      diplopia after surgery. Measures to minimize side effects are proposed. With
      meticulous technique, PBC is a straightforward, effective, and fast procedure
      that compares well with other percutaneous therapies for TN.

PMID- 22480981
TI  - Vascular anatomy in the lumbar spine investigated by three-dimensional computed
      tomography angiography: the concept of vascular window.
AB  - OBJECTIVE: To report an in vivo anatomic evaluation of prevertebral vessels in
      the lumbar spine using three-dimensional (3D) computed tomography (CT)
      angiography and to develop the concept of vascular window for surgical access to
      L4-5 and L5-S1 disks. METHODS: In 146 patients who were scheduled for anterior
      lumbar spine surgery, 3D CT angiography was performed preoperatively. Spinal
      disorders included degenerative disk disease (n = 120) and low-grade
      spondylolisthesis (n = 26). 3D reconstructions were obtained using the volume
      rendering technique. Level of aortic bifurcation and iliocavum confluence,
      presence of the ascending iliolumbar vein, presence of the central sacral
      vessels, and anatomic variations were analyzed. A vascular window at L5-S1 was
      defined as the "free vascular" area for the anterior part of the L5-S1 disk. A
      vascular window at L4-L5 was defined as the "free vascular" area for the left
      anterolateral part of the L4-5 disk. RESULTS: The level of aortic bifurcation was
      most often observed at L4 (64%). The iliocavum confluence occurred most
      frequently at L5 (44%). The iliolumbar ascending vein and central sacral vessels
      were identified in 84% and 72% of cases. Five (3.5%) anatomic variations were
      noted: right internal iliac vein draining into the left common iliac vein in two
      cases and tortuous vessels in three cases. A vascular window was measured to 34.5
      mm +/- 12 at L5-S1 and to 23 mm +/- 8 at L4-L5. The vascular window was <25 mm in
      approximately one in four patients at L5-S1 and in approximately two in three
      patients at L4-L5. CONCLUSIONS: This study confirms that vascular anatomy in the
      lumbar spine is characterized by a great variability that has significance for
      preoperative assessment. 3D CT angiography allowed for an effective evaluation of
      the relationships between the prevertebral vessels and the intervertebral disks
      at L4-L5 and L5-S1. Although adherence of vessels to the anterior ligament cannot
      be predicted by this technique, the concept of vascular windows investigated
      preoperatively by CT angiography could be helpful in predicting the need for
      vessel mobilization during anterior lumbar spine surgery.

PMID- 22480982
TI  - Malignant transformation of a vestibular schwannoma after gamma knife
      radiosurgery.
AB  - OBJECTIVE: To report a single case of malignant transformation of a vestibular
      schwannoma after radiosurgery and review the growing body of literature
      describing patients with malignant transformation of primary benign tumors after
      radiosurgery, including vestibular schwannoma. METHODS: A 46-year-old woman
      presented with right facial paresthesias and imaging consistent with a right
      sided vestibular schwannoma (volume approximately 18.5 cm(3)). RESULTS: The
      patient underwent subtotal resection followed by Gamma Knife radiosurgery (GKRS)
      6 months after surgery. Initial histology showed a benign vestibular schwannoma
      with an MIB-1 labeling index of 5.7%. At 43 months after GKRS, the patient
      underwent repeat subtotal resection of a benign vestibular schwannoma (MIB-1
      labeling index 7.4%). At 59 months after GKRS, she underwent a third resection,
      and histology showed frank malignant transformation (MIB-1 labeling index 33.8%).
      CONCLUSIONS: Malignant vestibular nerve tumors are extremely rare; only 18 cases
      have been reported in the literature. Our patient is the sixth pathologically
      confirmed case of malignant transformation after radiosurgery, supporting the
      contention that radiosurgery itself may play a causative role in transformation.
      In a histologically benign lesion, the presence of an elevated MIB-1 labeling
      index may predispose toward malignant transformation in the setting of adjuvant
      radiosurgery.

PMID- 22480983
TI  - Changes of metabolic and inflammatory markers in HIV infection: glucose, lipids,
      serum Hs-CRP and myeloperoxidase.
AB  - OBJECTIVE: HIV infection is exacerbated through additional pro-atherogenic
      mechanisms related to the processes of immune activation, inflammation,
      coagulation, and the modification of lipoproteins (e.g., particles of high
      density lipoprotein), contributing to increased cardiovascular risk. The aim of
      this study was to analyze the serum concentrations of myeloperoxidase (MPO) and
      other laboratory parameters in HIV-infected patients treated or not with
      antiretroviral drugs compared to non-infected individuals. MATERIALS/METHODS: The
      study included 154 volunteers: 47 non-infected individuals (control group - CON),
      27 infected and untreated individuals (NTARV group) and 80 treated individuals
      (TARV group). We analyzed the counts of CD4+ lymphocytes and the viral load of
      the infected patients, along with the blood count, fasting glucose, total serum
      cholesterol (CHOL), HDL cholesterol, LDL cholesterol, triglycerides, MPO and high
      sensitivity C-reactive protein (CRP) of all study participants. RESULTS: There
      were significant increases in glucose, CHOL, LDL cholesterol, and triglycerides
      in the TARV group and significant reductions in the levels of HDL cholesterol for
      the TARV and NTARV groups. Significantly elevated levels of Hs-CRP were observed
      only in the TARV group, while levels of MPO were significantly higher in the TARV
      and NTARV groups compared to the control group. A correlation of MPO with Hs-CRP
      (r=0.21, p=0.032) was observed for HIV-infected patients, but MPO did not
      correlate significantly with the other analyzed parameters. CONCLUSIONS: The
      investigation of early biomarkers for cardiovascular risk evaluation, such as
      MPO, contributes to the clinical monitoring of HIV-infected individuals. The
      serum levels of MPO correlated with Hs-CRP and were high in HIV-infected
      individuals, indicating a possible predictor of cardiovascular events in these
      patients.

PMID- 22480984
TI  - Adding sprints to continuous exercise at the intensity that maximises fat
      oxidation: implications for acute energy balance and enjoyment.
AB  - The objective was to examine the effect of adding sprints to continuous exercise
      at the intensity that maximises fat oxidation (Fat(max)) on energy expenditure,
      substrate oxidation, enjoyment and post-exercise energy intake in boys. Nine
      overweight and nine normal weight boys (8-12 years) attended the laboratory on
      three mornings. First, body anthropometrics, peak aerobic capacity and Fat(max)
      were assessed. On the remaining two sessions, resting metabolic rate was
      determined before participants completed 30 min of either continuous cycling at
      Fat(max) (MOD) or sprint interval exercise consisting of continuous cycling at
      Fat(max) interspersed with four-second maximal sprints every two minutes (SI).
      Energy expenditure and substrate oxidation were measured during exercise and for
      30 min post-exercise, while participants completed a modified Physical Activity
      Enjoyment Scale (PACES). This was followed by a buffet-like breakfast to measure
      post-exercise energy intake. Fat oxidation rate was similar between groups and
      protocols (P>0.05). Both groups expended more energy with SI compared to MOD,
      resulting from increased carbohydrate oxidation (P<0.05), which was not
      compensated by increased energy intake. Participants indicated that they
      preferred SI more than MOD, although there was no significant difference in PACES
      score between the protocols (P>0.05). In summary, the addition of short sprints
      to continuous exercise at Fat(max) increased energy expenditure without
      compromising fat oxidation or stimulating increased post-exercise energy intake.
      The boys preferred SI and did not perceive it to be any harder than MOD,
      indicating that sprint interval exercise should be considered in exercise
      prescription for this population.

PMID- 22480985
TI  - A comparative analysis of integrating visual information in local neuronal
      ensembles.
AB  - Spike directivity, a new measure that quantifies the transient charge density
      dynamics within action potentials provides better results in discriminating
      different categories of visual object recognition. Specifically, intracranial
      recordings from medial temporal lobe (MTL) of epileptic patients have been
      analyzed using firing rate, interspike intervals and spike directivity. A
      comparative statistical analysis of the same spikes from a local ensemble of four
      selected neurons shows that electrical patterns in these neurons display higher
      separability to input images compared to spike timing features. If the
      observation vector includes data from all four neurons then the comparative
      analysis shows a highly significant separation between categories for spike
      directivity (p=0.0023) and does not display separability for interspike interval
      (p=0.3768) and firing rate (p=0.5492). Since electrical patterns in neuronal
      spikes provide information regarding different presented objects this result
      shows that related information is intracellularly processed in neurons and
      carried out within a millisecond-level time domain of action potential
      occurrence. This significant statistical outcome obtained from a local ensemble
      of four neurons suggests that meaningful information can be electrically inferred
      at the network level to generate a better discrimination of presented images.

PMID- 22480986
TI  - "Beetrack": a software for 2D open field locomotion analysis in honey bees.
AB  - "Beetrack" is a complete software designed to analyze the 2D locomotor behavior
      of four simultaneous honey bees moving in petri dishes. Several dependent
      variables can be measured: traveled distance, number of jumps and % of
      immobility. A spatial analysis can also be performed to detect if the bees are
      using preferentially one part of the box. The software has been successfully
      tested with eight honey bees and promise to be an interesting tool in the
      pharmacology field.

PMID- 22480987
TI  - Single-cell resolution fluorescence imaging of circadian rhythms detected with a
      Nipkow spinning disk confocal system.
AB  - Single-point laser scanning confocal imaging produces signals with high spatial
      resolution in living organisms. However, photo-induced toxicity, bleaching, and
      focus drift remain challenges, especially when recording over several days for
      monitoring circadian rhythms. Bioluminescence imaging is a tool widely used for
      this purpose, and does not cause photo-induced difficulties. However,
      bioluminescence signals are dimmer than fluorescence signals, and are potentially
      affected by levels of cofactors, including ATP, O(2), and the substrate,
      luciferin. Here we describe a novel time-lapse confocal imaging technique to
      monitor circadian rhythms in living tissues. The imaging system comprises a
      multipoint scanning Nipkow spinning disk confocal unit and a high-sensitivity EM
      CCD camera mounted on an inverted microscope with auto-focusing function. Brain
      slices of the suprachiasmatic nucleus (SCN), the central circadian clock, were
      prepared from transgenic mice expressing a clock gene, Period 1 (Per1), and
      fluorescence reporter protein (Per1::d2EGFP). The SCN slices were cut out
      together with membrane, flipped over, and transferred to the collagen-coated
      glass dishes to obtain signals with a high signal-to-noise ratio and to minimize
      focus drift. The imaging technique and improved culture method enabled us to
      monitor the circadian rhythm of Per1::d2EGFP from optically confirmed single SCN
      neurons without noticeable photo-induced effects or focus drift. Using
      recombinant adeno-associated virus carrying a genetically encoded calcium
      indicator, we also monitored calcium circadian rhythms at a single-cell level in
      a large population of SCN neurons. Thus, the Nipkow spinning disk confocal
      imaging system developed here facilitates long-term visualization of circadian
      rhythms in living cells.

PMID- 22480988
TI  - Multiway array decomposition analysis of EEGs in Alzheimer's disease.
AB  - Methods for the extraction of features from physiological datasets are growing
      needs as clinical investigations of Alzheimer's disease (AD) in large and
      heterogeneous population increase. General tools allowing diagnostic regardless
      of recording sites, such as different hospitals, are essential and if combined to
      inexpensive non-invasive methods could critically improve mass screening of
      subjects with AD. In this study, we applied two state of the art multiway array
      decomposition (MAD) methods to extract unique features from electroencephalograms
      (EEGs) of AD patients obtained from multiple sites. In comparison to MAD,
      spectral-spatial average filter (SSFs) of control and AD subjects were used as
      well as a common blind source separation method, algorithm for multiple unknown
      signal extraction (AMUSE), and singular value decomposition (SVD) coupled to
      tensor unfolding. We trained a feed-forward multilayer perceptron (MLP) to
      validate and optimize AD classification from two independent databases. Using a
      third EEG dataset, we demonstrated that features extracted from MAD outperformed
      features obtained from SSFs AMUSE in terms of root mean squared error (RMSE) and
      reaching up to 100% of accuracy in test condition. We propose that MAD maybe a
      useful tool to extract features for AD diagnosis offering great generalization
      across multi-site databases and opening doors to the discovery of new
      characterization of the disease.

PMID- 22480989
TI  - Spin-orbit-induced photoelectron spin polarization in angle-resolved
      photoemission from both atomic and condensed matter targets.
AB  - The existence of highly spin polarized photoelectrons emitted from non-magnetic
      solids as well as from unpolarized atoms and molecules has been found to be very
      common in many studies over the past 40 years. This so-called Fano effect is
      based upon the influence of the spin-orbit interaction in the photoionization or
      the photoemission process. In a non-angle-resolved photoemission experiment,
      circularly polarized radiation has to be used to create spin polarized
      photoelectrons, while in angle-resolved photoemission even unpolarized or
      linearly polarized radiation is sufficient to get a high spin polarization. In
      past years the Rashba effect has become very important in the angle-resolved
      photoemission of solid surfaces, also with an observed high photoelectron spin
      polarization. It is the purpose of the present topical review to cross-compare
      the spin polarization experimentally found in angle-resolved photoelectron
      emission spectroscopy of condensed matter with that of free atoms, to compare it
      with the Rashba effect and topological insulators to describe the influence and
      the importance of the spin-orbit interaction and to show and disentangle the
      matrix element and phase shift effects therein.The relationship between the
      energy dispersion of these phase shifts and the emission delay of photoelectron
      emission in attosecond-resolved photoemission is also discussed. Furthermore the
      influence of chiral structures of the photo-effect target on the spin
      polarization, the interferences of different spin components in coherent
      superpositions in photoemission and a cross-comparison of spin polarization in
      photoemission from non-magnetic solids with XMCD on magnetic materials are
      presented; these are all based upon the influence of the spin-orbit interaction
      in angle-resolved photoemission.

PMID- 22480990
TI  - Cytokinin oxidase is involved in the regulation of cytokinin content by 24
      epibrassinolide in wheat seedlings.
AB  - Fast and stable 2-fold accumulation of cytokinins (CKs) was detected initially in
      roots and then in shoots of 4-day-old wheat (Triticum aestivum L.) seedlings in
      the course of their treatment with 0.4MUM 24-epibrassinolide (EBR). Elevated
      cytokinin level has been maintained only in the presence of EBR, while the
      hormone removal has led to return of cytokinin concentration to the control level
      initially in the roots and then in the shoots. EBR-induced accumulation of
      cytokinins was accompanied by inhibition of both cytokinin oxidase (CKX)
      (cytokinin oxidase/dehydrogenase, EC 1.5.99.12) activity and expression of the
      gene coding for this enzyme, and on the contrary the decline in CKs level
      resulted in increase in these characteristics up to the control level in roots
      and then in shoots. Sharp accumulation of cytokinin O-glucosides has been
      discovered in response to EBR-treatment suggesting fast EBR-induced activation of
      production of cytokinins, which excessive amounts were transferred into the
      storage forms. The obtained data provide evidence for the involvement of EBR in
      regulation of cytokinin level in wheat seedlings.

PMID- 22480991
TI  - Use of two bacteria for biological control of bayoud disease caused by Fusarium
      oxysporum in date palm (Phoenix dactylifera L) seedlings.
AB  - The Bayoud, caused by Fusarium oxysporum f. sp. albedinis (Foa), is the most
      destructive disease of date palm (Phoenix dactylifera L) in Morocco and Algeria,
      with no effective control strategy yet available. In this work, two bacteria,
      Bacillus amyloliquefaciens strain Ag1 (Ag) and Burkholderia cepacia strain Cs5
      (Cs), were examined for their potential to control this disease. Both bacterial
      strains inhibited both growth and sporulation of Foa. They released compounds
      into the culture medium, which resulted into cytological changes in Foa's
      mycelial structure. When Jihel-date palm plantlets, a susceptible cultivar, were
      induced with these bacteria, the size of the necrosis zone, which reflected the
      spreading of the pathogen, was reduced by more than 70%, as compared with
      uninduced controls. To further investigate the mechanisms of such disease
      reduction, phenolic compounds and peroxidase activity were assessed. One month
      after inoculation, date palm defense reactions against Foa were different
      depending on the bacterium used, B. cepacia led to higher accumulation of
      constitutive caffeoylshikimic acid isomers while B. amyloliquefaciens triggered
      the induction of new phenolic compounds identified as hydroxycinnamic acid
      derivatives. Peroxidase activity has also been stimulated significantly and
      varied with the bacterial strain used and with Foa inoculation. These results add
      to the promising field of investigation in controlling Bayoud disease.

PMID- 22480992
TI  - Effects of waterborne copper nanoparticles and copper sulphate on rainbow trout,
      (Oncorhynchus mykiss): physiology and accumulation.
AB  - Emerging data suggests that some types of nanoparticles (NPs) are toxic to fish,
      and given the well-known toxicity of dissolved metals, there are also concerns
      about whether metal-containing NPs present a similar or different hazard to metal
      salts. In this study, juvenile rainbow trout were exposed in triplicate to either
      a control, 20 or 100 MUg l-1 of either Cu as CuSO4 or Cu-NPs (mean primary
      particle size, 87+/-27 nm) in a semi-static aqueous exposure regime. Fish were
      sampled at days 0, 4, and 10 for tissue trace elements, haematology, and
      biochemistry. By day 4, fish from the 100 MUg l-1 Cu as CuSO4 treatment showed
      85% mortality (treatment subsequently terminated) compared to 14% in the 100 MUg
      l-1 Cu-NP exposed fish. Mortality at day 10 was 4, 17, 10, and 19% in the
      control, 20 MUg l-1 Cu as CuSO4, 20 and 100 MUg l-1 Cu-NP treatments,
      respectively. Copper accumulation was seen in the gills of fish from all Cu
      treatments, and was statistically significant in both CuSO4 treatments at day 4
      and all Cu treatments at day 10 compared to controls. No statistically
      significant Cu accumulation was seen in the spleen, brain or muscle of fish from
      any treatment, although an elevation in intestinal Cu was seen in the high Cu-NP
      treatment throughout. There were some transient changes in haematology and
      depletion of plasma Na+ that was treatment-related, with some differences between
      the nano form and metal salt, but Cu-NPs were not overtly haemolytic. A 6-fold
      decrease in branchial Na+/K+-ATPase activity in all Cu treatments (compared to
      controls), depletion of plasma and carcass ion concentrations suggest that Cu-NPs
      are an ionoregulatory toxicant to rainbow trout. Statistically significant
      decreases in Na+/K+-ATPase activity were also seen in the brains and intestine,
      and whilst there was no material-type effect in the former, this was only
      observed in the gut of fish exposed to 100 MUg l-1 Cu-NPs. There were material
      dependent changes in tissue thiobarbituric acid reactive substances (TBARS), and
      in the gill the Cu-NPs caused a larger (though non-significant compared to
      control) increase in TBARS than the equivalent metal salt treatment (the latter
      actually being significantly reduced compared to all other treatments). Overall,
      these data show that Cu-NPs have similar types of toxic effects to CuSO4, which
      can occur at lower tissue Cu concentrations than expected for the dissolved
      metal.

PMID- 22480993
TI  - A breath of Twitter.
AB  - The use of online social networks among physicians and physicians-in-training is
      similar to that of the general population. Patients also use online social
      networks to communicate and exchange information with other patients who have
      similar conditions and with health professionals, something which is not free
      from ethical problems. In any case, online social networks have penetrated
      clinical practice irreversibly. Twitter is an effective social communication tool
      used for many different purposes. It has been massively adopted in many sectors
      including healthcare. The article explores its usefulness for respiratory
      physicians, focusing in four areas: 1) Access to generic and scientific
      information, 2) Contact with the professional community, 3) Public health, 4)
      Relationship with patients.

PMID- 22480994
TI  - Progress in the treatment of lymphangioleiomyomatosis: from bench to bedside.

PMID- 22480995
TI  - Genome-wide association study of skin complex diseases.
AB  - Complex diseases are caused by both genetic and environmental factors. Over
      decades, scientists endeavored to uncover the genetic myth of complex diseases by
      linkage and association studies. Since 2005, the genome-wide association study
      (GWAS) has been proved to be the most powerful and efficient study design thus
      far in identifying genetic variants that are associated with complex diseases.
      More than 230 complex diseases and traits have been investigated by this
      approach. In dermatology, 10 skin complex diseases have been investigated, a
      wealth of common susceptibility variants conferring risk for skin complex
      diseases have been discovered. These findings point to genes and/or loci involved
      in biological systems worth further investigating by using other methodologies.
      Certainly, as our understanding of the genetic etiology of skin complex diseases
      continues to mature, important opportunities will emerge for developing more
      effective diagnostic and clinical management tools for these diseases.

PMID- 22480996
TI  - Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung
      cancer.
AB  - There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory
      drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer,
      in particular in never-smokers, is unclear. Information on past or current use of
      anti-inflammatory medication was obtained in 398 Chinese female primary lung
      cancer cases and 814 controls in a hospital-based study in Singapore. 65% of
      cases and 88% of controls were never-smokers. Controls were excluded if they had
      been admitted for conditions associated with aspirin or NSAID use (n=174).
      Regular aspirin use (twice a week or more, for a month or more) was associated
      with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence
      intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers).
      Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills
      was uncommon and no association with lung cancer was detected. Our results
      suggest that aspirin consumption may reduce lung cancer risk in Asian women and
      are consistent with current understanding of the role of cyclooxygenase in lung
      carcinogenesis.

PMID- 22480997
TI  - Prevalence and contributors to fatigue in individuals hospitalized with advanced
      cancer: a prospective, observational study.
AB  - BACKGROUND: Although fatigue affects over 75% of patients with advanced cancer,
      changes over time in symptoms and antecedents have not been described in the
      acute care setting. OBJECTIVES: To determine the prevalence, in patients with
      advanced cancer, of fatigue and anaemia on admission, describe strategies used to
      treat anaemia, observe changes in fatigue over ten days, and determine factors
      associated with fatigue. DESIGN: Prospective, observational study. SETTINGS AND
      PARTICIPANTS: In two Swiss tertiary care hospitals, a convenience sample of
      patients (N=103) was recruited at admission and followed up at days six (n=76)
      and ten (n=53). Patients were admitted because of new and/or worsening symptoms,
      deteriorating health status, or complications. They received measures aimed at
      symptom control and disease modifying interventions. METHODS: Clinical and
      sociodemographic data were collected on selected patients who were able to
      complete a test battery of validated measures. Assessment was undertaken on
      hospital admission and on days six and ten post-admission. FINDINGS: At
      admission, according to the suggested cut-off score of 43 for the FACIT-Fatigue
      scale, 87% of participants were experiencing cancer-related fatigue. Fatigue
      varied greatly within and among patients. Data on anaemia were available for 100
      patients, of whom 62% were anaemic on admission. Severe and life threatening
      anaemia were mostly treated with red blood cell transfusions. Over time, fatigue
      decreased for patients who improved enough to be discharged (p<0.001) but not for
      those who withdrew from the study, most of whom did so due to worsening health.
      In multiple regression analysis, younger patients and patients with lower
      functional status, higher scores for depression, and more other anaemia-related
      symptoms experienced more fatigue. The variables examined explained 62% of
      variance in fatigue. CONCLUSIONS: Fatigue was common in hospitalized patients
      with advanced cancer and the majority were anaemic. Based on these data,
      monitoring and treating fatigue and anaemia over a ten-day hospital stay seem to
      be supported. The variable trajectories call for interventions carefully tailored
      to individual patients. The results should be considered as a first step to
      exploring fatigue in these patients.

PMID- 22480998
TI  - Alterations in stress responses of the hypothalamic-pituitary-adrenal axis in
      small for gestational age infants.
AB  - Mounting epidemiologic evidence and animal models suggest that stressful
      conditions during the intrauterine period may increase susceptibility to several
      adult conditions, including metabolic syndrome, cardiovascular disease, and
      psychiatric disorders. Increased cortisol levels due to alterations in the
      regulation of the hypothalamic-pituitary-adrenal (HPA) axis are believed to be
      one mediating mechanism. Infants born after significant exposure to stressful
      conditions are often small for gestational age (SGA) based on standardized growth
      norms. Lifelong programming of the HPA axis has been proposed as a mechanism to
      explain the association between SGA infants and adult disease. However, few
      studies have measured HPA axis function proximal to birth as done in this study
      of SGA infants during the first week of life. Participants included 37 infants in
      two groups based on birth size (gestational age range: 34-41weeks). SGA infants
      were <10th percentile for age (n=21) and appropriate for gestational age (AGA)
      infants (n=16) were from 20 to 90th percentile for age. Cortisol response to a
      heel lance for blood collection was measured for all infants. Hierarchical Linear
      Modeling was used to test the effect of AGA/SGA group status on cortisol
      trajectories in response to the stressor. Group was a significant predictor of
      quadratic slopes (t=2.84, chi(2)=8.19, p=.004) after controlling for the effect
      of group on intercepts and linear slopes. Predicted growth curves for ln-cortisol
      were plotted for each group based on regression coefficients. The predicted
      curves capture the significant group difference in trajectories, as well as the
      blunted response for the SGA group and the robust peak in cortisol production in
      response to the stressor for the AGA group. This evidence suggests SGA neonates
      have blunted HPA axis responses to stressors in comparison to AGA infants. These
      findings are consistent with animal models showing that adverse intrauterine
      conditions can result in blunted cortisol responses to acute stressors and may
      provide a mechanism for adult susceptibility to disease for individuals that are
      SGA at birth.

PMID- 22480999
TI  - Provision of out-of-hours interventional radiology services in Scotland.
AB  - AIM: To evaluate the availability of out-of-hours (OOH) interventional radiology
      (IR) services in Scotland and discuss implications for service redesign.
      MATERIALS AND METHODS: Data were gathered via a survey conducted by telephone/e
      mail interview. The setting was hospitals in Scotland with acute medical and/or
      surgical beds. The interviewees were consultant interventional radiologists
      representing each of the 14 geographical Health Boards in Scotland. RESULTS:
      Three of the 14 geographical Health Boards provided a formal, prospectively
      planned OOH IR service in at least one hospital. Fourteen of the 34 acute
      hospitals provided an in-hours IR service, which includes endovascular
      haemorrhage control. Eight of the 34 acute hospitals had formal, prospectively
      planned on-call IR arrangements, 12 had an ad-hoc service, and 20 transferred
      patients to other facilities. Thirty-eight of the 223 consultant radiologists in
      Scotland were able to perform endovascular haemorrhage control procedures: only
      18 of these 38 (47%) were included in on-call rotas. A further 42 radiologists
      were able to perform nephrostomy and a further 61 were able to perform abscess
      drainage. Eighty-two radiologists did not perform any interventional procedures.
      CONCLUSIONS: The provision of OOH IR services in Scotland is limited and
      available resources, both skills and equipment, are being underutilized. These
      data will be used to inform a process of OOH IR service redesign in Scotland.

PMID- 22481000
TI  - MRI findings of isoniazid-induced central nervous system toxicity in a child.

PMID- 22481001
TI  - [Von Hippel-Lindau disease in a patient with l-2-hydroxyglutaric aciduria].

PMID- 22481002
TI  - Efficient utilization of hemicellulose hydrolysate for propionic acid production
      using Propionibacterium acidipropionici.
AB  - Hemicellulose, which contains glucose, xylose, and arabinose as the 3 main
      sugars, is an important renewable source for biorefinery. In this study,
      propionic acid production from glucose, xylose, or arabinose using
      Propionibacterium acidipropionici ATCC 4875 was investigated. Using xylose, the
      predominant sugar in hemicellulose, a final propionic acid concentration of 53.2
      g l(-1) was obtained via fed-batch fermentation. Using corncob molasses, a waste
      by-product from xylitol production as a representative of hemicellulose
      hydrolysate, the final concentration of propionic acid was 71.8 g l(-1), with a
      corresponding productivity of 0.28 g l(-1) h(-1). The present study suggests that
      hemicellulose hydrolysate is an excellent carbon source for efficient propionic
      acid production by this strain.

PMID- 22481003
TI  - Reprocessed polylactide: studies of thermo-oxidative decomposition.
AB  - The combustion process of virgin and reprocessed polylactide (PLA) was simulated
      by multi-rate linear non-isothermal thermogravimetric experiments under O(2). A
      complete methodology that accounted on the thermal stability and emission of
      gases was thoroughly developed. A new model, Thermal Decomposition Behavior, and
      novel parameters, the Zero-Decomposition Temperatures, were used to test the
      thermal stability of the materials under any linear heating rate. The release of
      gases was monitored by Evolved Gas Analysis with in-line FT-IR analysis. In
      addition, a kinetic analysis methodology that accounted for variable activation
      parameters showed that the decomposition process could be driven by the formation
      of bubbles in the melt. It was found that the combustion technologies for virgin
      PLA could be transferred for the energetic valorization of its recyclates.
      Combustion was pointed out as appropriate for the energetic valorization of PLA
      submitted to more than three successive reprocessing cycles.

PMID- 22481004
TI  - Pubertal effects of 17alpha-methyltestosterone on GH-IGF-related genes of the
      hypothalamic-pituitary-liver-gonadal axis and other biological parameters in
      male, female and sex-reversed Nile tilapia.
AB  - The influence of 17alpha-methyltestosterone (MT) on growth responses, biological
      parameters and the expression of genes involved in the GH-IGF pathway of the
      hypothalamic-pituitary-liver-gonadal axis were investigated in female, male, and
      sex-reversed Nile tilapia to evaluate the relationship between sex and MT-induced
      changes in these parameters. Female fish had a lower growth rate than male and
      sex-reversed fish, and MT increased growth performance and duodenal villi in
      females. Most but not all biological parameters of sex-reversed fish were similar
      to those of male fish. Male fish had higher red blood cell counts and hemoglobin
      levels than female and sex-reversed fish, suggesting that these hematological
      indices reflect a higher metabolic rate in male fish. Greater blood triglyceride
      levels indicated the vitellogenin process in female fish. MT increased the
      alternative complement activity in female fish (P<0.05). Sex and MT had no
      significant effects on the hypothalamic mRNAs of GHRH and PACAP. Although not
      statistically significant, females tended to have higher GH mRNA levels than male
      and sex-reversed fish. Additionally, MT tended to decrease and increase GH mRNA
      levels in female and male fish, respectively. There were significant differences
      among sexes in the expression of GHR, and IGF mRNAs at the peripheral level in
      the liver and gonads. Females had lower hepatic GHRs and higher ovarian GHRs than
      male and sex-reversed fish. While the mRNA levels of IGF-1 were lower in the
      ovary, the levels of IGF-2 were higher compared with those in testes. A
      significant correlation between GHRs and IGFs was demonstrated in the liver and
      gonad (except for IGF-1). Multiple regression analysis showed a significant
      relationship between GH mRNA and both GHRs and IGFs in the liver and gonad. MT
      exerted androgenic and, to some extent, estrogenic effects on several
      physiological parameters and GH-IGF action.

PMID- 22481005
TI  - Comparative Effectiveness Research and the Surveillance, Epidemiology, and End
      Results database: what is Comparative Effectiveness Research (CER) and why is it
      important?

PMID- 22481006
TI  - Overview of the Surveillance, Epidemiology, and End Results database: evolution,
      data variables, and quality assurance.

PMID- 22481007
TI  - Prophylactic cranial irradiation: do benefits outweigh neurocognitive impact?

PMID- 22481008
TI  - Prediction models, nomograms, and staging validation with the Surveillance,
      Epidemiology, and End Results database: using Surveillance, Epidemiology and End
      Results (SEER) program to create prediction models.

PMID- 22481009
TI  - Limitations and biases of the Surveillance, Epidemiology, and End Results
      database.

PMID- 22481010
TI  - Outcomes according to presentation with versus without cardiogenic shock in
      patients with left main coronary artery stenosis and acute myocardial infarction.
AB  - This study is aimed at evaluating 1-year clinical outcomes and their predictors
      in patients with unprotected left main coronary artery (ULMCA)-related acute
      myocardial infarction (AMI). In total 248 patients diagnosed with AMI involving
      the ULMCA as the culprit vessel and registered in the Korean Acute Myocardial
      Infarction database were enrolled in this study. Patients were divided according
      to the absence (shock-, n = 206) or presence (shock+, n = 42) of cardiogenic
      shock at initial presentation. Independent risk factors of in-hospital cardiac
      death associated with ULMCA-related AMI were elucidated by multivariate
      regression analysis. In-hospital mortality rates were 8.7% in the shock- group
      and 47.6% in the shock+ group (p = 0.001). During 1-year follow-up after
      discharge, major adverse cardiac events developed in 16.3% of patients in the
      shock- group and 18.2% of patients in the shock+ group (p = 0.828); cardiac
      death, MI, and ischemia-driven target vessel revascularization were similar
      between the 2 groups at 1 year. On multivariate analysis, initial shock
      presentation (odds ratio 8.9, confidence interval 4.1 to 19.2, p = 0.004) and
      left ventricular ejection fraction <30% (odds ratio 7.6, confidence interval 2.7
      to 21.1, p = 0.001) were independent risk factors of in-hospital cardiac death
      associated with ULMCA-related AMI. In conclusion, almost 1/2 of patients with
      ULMCA-related AMI presenting with cardiogenic shock had a fatal in-hospital
      outcome compared to <10% of those without cardiogenic shock; however, clinical
      outcomes after survival of the in-hospital period were not different between
      these groups.

PMID- 22481011
TI  - Importance of ventricular tachycardia storms not terminated by implantable
      cardioverter defibrillators shocks in patients with CASQ2 associated
      catecholaminergic polymorphic ventricular tachycardia.
AB  - In this study, the clinical and implantable cardioverter-defibrillator (ICD)
      related follow-up of patients with catecholaminergic polymorphic ventricular
      tachycardia (CPVT) with homogenous missense mutations in CASQ2 was summarized.
      Patients were followed in a pediatric cardiology clinic and an ICD clinic. All
      patients were treated with high-dose beta blockers. ICDs were recommended for
      patients who remained symptomatic despite medical treatment. Twenty-seven
      patients were followed for 1 to 15 years (median 9). Twenty patients (74%) were
      symptomatic at diagnosis; 13 (65%) remained symptomatic after treatment with high
      dose beta blockers and thus were advised to receive ICDs. Eight of these patients
      refused ICDs, and eventually 6 (75%) died suddenly. Four of the 5 patients who
      received ICDs had ventricular tachycardia storms treated but not terminated by
      recurrent ICD shocks. These ventricular tachycardia storms (2 episodes in 2
      patients and 1 episode in 2 patient) terminated spontaneously after finishing the
      programmed ICD shocks, without degeneration to ventricular fibrillation. None of
      the patients who received ICDs died. In conclusion, patients with CASQ2
      associated CPVT should be recommended to receive ICDs to prevent sudden death
      when medical therapy is not effective. These patients may have recurrent
      ventricular tachycardia storms treated but not terminated by recurrent ICD
      shocks, without degeneration to ventricular fibrillation.

PMID- 22481012
TI  - Effect of improving glycemic control in patients with type 2 diabetes mellitus on
      low-density lipoprotein size, electronegative low-density lipoprotein and
      lipoprotein-associated phospholipase A2 distribution.
AB  - The aim of this study was to determine the effect of intensified hypoglycemic
      therapy in patients with type 2 diabetes mellitus on the distribution of
      lipoprotein-associated phospholipase A2 (Lp-PLA2) activity between high-density
      lipoprotein and low-density lipoprotein (LDL) and its relation with the lipid
      profile and other qualitative properties of LDL. Forty-two patients with type 2
      diabetes on the basis of poor glycemic control and normal or near normal LDL
      cholesterol were recruited. Lifestyle counseling and pharmacologic hypoglycemic
      therapy were intensified to improve glycemic control, but lipid-lowering therapy
      was unchanged. At 4 +/- 2 months, glycosylated hemoglobin had decreased by a mean
      of 2.1%, but the only effect on the lipid profile were statistically significant
      decreases in nonesterified fatty acids and apolipoprotein B concentration. LDL
      size increased and the proportion of electronegative LDL decreased significantly.
      In parallel, total Lp-PLA2 activity decreased significantly, promoting a
      redistribution of Lp-PLA2 activity toward a higher proportion in high-density
      lipoprotein. Improvements in glycemic control led to more marked changes in Lp
      PLA2 activity and distribution in patients with diabetes who had not received
      previous lipid-lowering therapy. In conclusion, optimizing glycemic control in
      patients with type 2 diabetes promotes atheroprotective changes, including larger
      LDL size, decreased electronegative LDL, and a higher proportion of Lp-PLA2
      activity in high-density lipoprotein.

PMID- 22481013
TI  - Comparison of outcomes of weekend versus weekday admissions for atrial
      fibrillation.
AB  - Previous studies have identified a "weekend effect" in terms of a poor outcome
      for patients hospitalized with various acute medical conditions. The aim of our
      study was to investigate whether weekend admissions for atrial fibrillation (AF)
      result in worse outcomes than those admitted on weekdays. In the Nationwide
      Inpatient Sample 2008 database, we identified a total of 86,497 discharges with a
      primary discharge diagnosis of AF. The use of a cardioversion procedure for AF on
      weekends was lower than that on a weekday (7.9% vs 16.2%; p <0.0001; odds ratio
      0.5, 95% confidence interval 0.45 to 0.55, p <0.0001). After adjusting for
      patient and hospital characteristics and disease severity, the adjusted in
      hospital mortality odds were greater for weekend admissions (odds ratio 1.23, 95%
      confidence interval 1.03 to 1.51; p <0.0001). The length of stay was
      significantly longer for weekend admissions. In conclusion, patients admitted
      with AF on weekends had lower odds of undergoing a cardioversion procedure and
      greater odds of dying.

PMID- 22481014
TI  - Effects of curcuminoids on frequency of acute myocardial infarction after
      coronary artery bypass grafting.
AB  - It is well established that myocardial infarction (MI) associated with coronary
      artery bypass grafting (CABG) predicts a poor outcome. Nevertheless,
      cardioprotective therapies to limit myocardial injury after CABG are lacking.
      Previous studies have shown that curcuminoids decrease proinflammatory cytokines
      during cardiopulmonary bypass surgery and decrease the occurrence of
      cardiomyocytic apoptosis after cardiac ischemia/reperfusion injury in animal
      models. We aimed to evaluate whether curcuminoids prevent MI after CABG compared
      to placebo. The 121 consecutive patients undergoing CABG were randomly allocated
      to receive placebo or curcuminoids 4 g/day beginning 3 days before the scheduled
      surgery and continued until 5 days after surgery. The primary end point was
      incidence of in-hospital MI. The secondary end point was the effect of
      curcuminoids on C-reactive protein, plasma malondialdehyde, and N-terminal pro-B
      type natriuretic peptide levels. Baseline characteristics were comparable between
      the curcuminoid and placebo groups. Mean age was 61 +/- 9 years. On-pump CABG
      procedures were performed in 51.2% of patients. Incidence of in-hospital MI was
      decreased from 30.0% in the placebo group to 13.1% in the curcuminoid group
      (adjusted hazard ratio 0.35, 0.13 to 0.95, p = 0.038). Postoperative C-reactive
      protein, malondialdehyde, and N-terminal pro-B-type natriuretic peptide levels
      were also lower in the curcuminoid than in the placebo group. In conclusion, we
      demonstrated that curcuminoids significantly decreased MI associated with CABG.
      The antioxidant and anti-inflammatory effects of curcuminoids may account for
      their cardioprotective effects shown in this study.

PMID- 22481015
TI  - A computed tomography-based coronary lesion score to predict acute coronary
      syndrome among patients with acute chest pain and significant coronary stenosis
      on coronary computed tomographic angiogram.
AB  - We tested the hypothesis that morphologic lesion assessment helps detect acute
      coronary syndrome (ACS) during index hospitalization in patients with acute chest
      pain and significant stenosis on coronary computed tomographic angiogram (CTA).
      Patients who presented to an emergency department with chest pain but no
      objective signs of myocardial ischemia (nondiagnostic electrocardiogram and
      negative initial biomarkers) underwent CT angiography. CTA was analyzed for
      degree and length of stenosis, plaque area and volume, remodeling index, CT
      attenuation of plaque, and spotty calcium in all patients with significant
      stenosis (>50% in diameter) on CTA. ACS during index hospitalization was
      determined by a panel of 2 physicians blinded to results of CT angiography. For
      lesion characteristics associated with ACS, we determined cutpoints optimized for
      diagnostic accuracy and created lesion scores. For each score, we determined the
      odds ratio (OR) and discriminatory capacity for the prediction of ACS. Of the
      overall population of 368 patients, 34 had significant stenosis and 21 of those
      had ACS. Scores A (remodeling index plus spotty calcium: OR 3.5, 95% confidence
      interval [CI] 1.2 to 10.1, area under curve [AUC] 0.734), B (remodeling index
      plus spotty calcium plus stenosis length: OR 4.6, 95% CI 1.6 to 13.7, AUC 0.824),
      and C (remodeling index plus spotty calcium plus stenosis length plus plaque
      volume <90 HU: OR 3.4, 95% CI 1.5 to 7.9, AUC 0.833) were significantly
      associated with ACS. In conclusion, in patients presenting with acute chest pain
      and stenosis on coronary CTA, a CT-based score incorporating morphologic
      characteristics of coronary lesions had a good discriminatory value for detection
      of ACS during index hospitalization.

PMID- 22481016
TI  - Influence of attenuation correction on transient left ventricular dilation in
      dual isotope myocardial perfusion imaging in patients with known or suspected
      coronary artery disease.
AB  - The aim of this study was to assess the effect of attenuation correction (AC) on
      left ventricular (LV) volumes and LV transient ischemic dilatation (TID) during
      dual-isotope single-photon emission computer tomographic (SPECT) myocardial
      perfusion imaging (MPI). Ninety-six patients (mean age 58 +/- 11 years, 15%
      women, 38 patients completed exercise and 58 dipyridamole pharmacologic stress
      tests) assessed for known or suspected coronary artery disease underwent dual
      isotope thallium-201 rest and technetium-99m sestamibi stress SPECT MPI with
      computed tomography-based AC. The TID ratio was calculated separately for non-AC
      and AC SPECT MPI studies as the ratio of the LV endocardial volume at stress
      divided by LV endocardial volume at rest. The mean and range of the gated LV
      ejection fraction during exercise and pharmacologic stress was 54 +/- 12% (29% to
      80%) and 58 +/- 12% (27% to 80%), respectively. In the exercise stress group, the
      same mean LV endocardial volumes in non-AC and AC stress (76.4 +/- 30 and 76.5 +/
      28) and rest (66.3 +/- 26 and 66.4 +/- 24) studies were found (p = 0.90). There
      was no statistical difference between the mean exercise TID ratio in non-AC and
      AC studies (1.27 vs 1.31, respectively, p = 0.10). The same mean LV endocardial
      volumes in non-AC and AC in pharmacologic stress (79.9 +/- 42 and 80 +/- 41) and
      rest (71.4 +/- 41 and 72.3 +/- 37), respectively, were found (p = 0.50). There
      was no statistical difference between the mean dipyridamole TID ratio in non-AC
      and AC studies (1.20 vs 1.17, respectively, p = 0.10). In conclusion, LV volumes
      and TID indexes obtained on SPECT MPI with exercise or pharmacologic stress using
      dipyridamole are not affected by AC.

PMID- 22481017
TI  - Coronary computed tomographic angiography for prediction of procedural and
      intermediate outcome of bypass grafting to left anterior descending artery
      occlusion with failed visualization on conventional angiography.
AB  - Conventional coronary angiography (CCA) has considerable limitations regarding
      visualization of distal vessel segments in chronic total occlusion. We assessed
      the ability of coronary computed tomographic angiography (CCTA) to predict the
      success of coronary artery bypass grafting (CABG) to the chronically occluded
      left anterior descending coronary artery (LAD) incompletely visualized on CCA.
      Thirty symptomatic patients rejected for CABG on the basis of the CCA findings
      underwent preoperative CCTA before intended transmyocardial laser
      revascularization. The LAD was explored operatively in all patients, and CABG to
      the LAD was attempted if the distal vessel was suitable for anastomosis. The
      procedural outcome of CABG and the 6-month patency of the left internal mammary
      artery graft at follow-up CCTA were defined as the primary and secondary end
      point, respectively. The primary and secondary end points were achieved in 80%
      and 77% of patients, respectively. We found a significant correlation between the
      intraoperative and computed tomographic measurement of distal LAD diameter (R =
      0.428, p = 0.037). On multivariate analysis, the maximum diameter of the distal
      LAD by CCTA (odds ratio 8.16, p = 0.043) was the only independent correlate of
      procedural success of CABG. A cutoff value of 1.5 mm for the mean distal LAD
      diameter predicted left internal mammary artery graft patency with 100%
      specificity and 83% sensitivity. Successful CABG resulted in significant
      improvements in angina class and left ventricular function in LAD segments at 6
      months of follow-up. In conclusion, CCTA predicted both the procedural and the
      intermediate outcome of CABG to chronic LAD occlusion with failed visualization
      on CCA.

PMID- 22481018
TI  - Structure-based characterization of canine-human chimeric uricases and its
      evolutionary implications.
AB  - Uricase was lost in hominoids during primate evolution, but the inactivation
      mechanism remains controversial. To investigate the inactivation process of
      hominoid uricase, chimeric constructions between canine and human uricase were
      employed to screen the target regions that may contain labile or inactivated
      mutations in deduced human uricase. Four chimeric uricases were constructed and
      showed different enzymatic characteristics. Homology modeling, rational site
      directed mutagenesis and DNA alignment were used to analyze the changes. Arg119
      is conserved in functional mammalian uricases and its side-chains are crucial in
      maintaining the stability of the beta-barrel core. A single CGT (Arg) to CAT
      (His) mutation at codon 119 that is shared by the human and great ape clade
      greatly reduces this stability and could cause the loss of uricase activity. We
      speculate that this missense mutation occurred first and inactivated the uricase
      protein in humans and great apes and that later the known nonsense mutation at
      codon 33 occurred and silenced the uricase gene. A single GTC (Val) to GCC (Ala)
      mutation at codon 296 in canine uricase is regarded as deleterious structural
      mutation, but such kinds of deleterious mutations have been widely accumulated in
      extant mammalian uricases. We speculate that a reduction in uricase activity has
      been an evolutionary tendency in mammals. Moreover, from structure-activity
      analysis of helix 2 in ancestral primate uricase, we suggest that before the
      inactivation of hominoid uricase, deleterious structural evolutionary changes had
      occurred in ancestral primates. The loss of hominoid uricase should be caused by
      progressive multistep mutations rather than a single mutation event.

PMID- 22481019
TI  - LASP-1, a novel urinary marker for detection of bladder cancer.
AB  - OBJECTIVES: The LIM and SH3 (LASP)-1 protein is a focal adhesion protein that has
      been linked to oncogenesis. The aim of this study was to evaluate the diagnostic
      use of the detection of LASP-1 in tumor specimens and in urine for noninvasive
      detection of transitional cell carcinoma (TCC). MATERIALS AND METHODS:
      Immunohistochemical staining for LASP-1 was performed on 72 archived bladder
      tumor specimens, and LASP-1 content was measured in 132 spontaneous urine sample
      sediments by Western blot analysis. RESULTS: In the histologic specimens,
      immunohistochemical staining for LASP-1 showed abundant expression throughout the
      urothelium of the bladder and ureter. However, modest overexpression of LASP-1
      was observed in the TCC specimens. Measurement of the LASP-1 protein
      concentrations in urinary cell pellets from healthy donors and bladder cancer
      patients was highly sensitive for the presence of TCC. The cut-off value was
      determined by receiver operating characteristic (ROC) analysis. When a cut-off
      value of 1 ng LASP-1/500 MUl of urine was used, the sensitivity, specificity, and
      positive and negative predictive values of the assay were 83.1%, 85.3%, 83.1%,
      and 80.6%, respectively.The increased urinary LASP-1 content in TCC patients was
      attributable in part to a specific increase in cell shedding presumably caused by
      changes in cell adhesion, as confirmed by LASP-1 knockdown. Contamination with
      erythrocytes above 250 cells/MUl and urinary infection gave false positive
      results and are therefore sample exclusion criteria. CONCLUSIONS: In the absence
      of urinary infection or gross hematuria, urinary LASP-1 level is a promising
      marker for transitional cell carcinoma.

PMID- 22481020
TI  - Modified orthotopic spiral ileal bladder substitution: surgical technique and
      long-term results.
AB  - OBJECTIVES: The objectives of this study are to introduce the surgical technique
      of a modified spiral orthotopic ileal neobladder and to assess the long-term
      outcomes. PATIENTS AND METHODS: Between January 1998 and January 2006, 44 male
      and 7 female patients with bladder cancer received radical cystectomy (RC) and
      pelvic lymphadenectomy. An ileal segment 40 cm to 45 cm long was isolated to
      create a spiral orthotopic ileal neobladder, and the ureters were implanted into
      the reservoir using a non-refluxing split-cuff nipple technique. Preoperative,
      perioperative, and postoperative data were collected. Complications were
      classified as early (less than 3 months after surgery) or late (more than 3
      months after surgery). Continence incidence and urodynamic studies were evaluated
      5 years after surgery. Duration of follow-up was an average of 95 months (range
      60-156 months). RESULTS: There were no perioperative deaths. The mean operative
      time was 315 +/- 34 minutes. The mean blood loss was 783 +/- 316 ml. There were
      31 early complications in 21 patients (41%) and 42 late complications in 30
      patients (59%). Urodynamic studies showed the maximum neobladder capacity to be
      500 +/- 71 ml, maximum flow rate to be 16 +/- 5 ml/s and post-voiding residual
      (PVR) to be 50 +/- 44 ml. Postoperative continence was excellent with a daytime
      continence rate of 90% and a nocturnal continence rate of 78% 5 years after
      surgery. CONCLUSIONS: The modified spiral neobladder is easy to perform and
      allows for excellent long-term results with regard to complications and
      continence.

PMID- 22481021
TI  - A rare complication of hereditary epidermolysis bullosa: esophageal carcinoma in
      recessive dystrophic epidermolysis bullosa inversa.

PMID- 22481022
TI  - Detection of CD34, TdT, CD56, CD2, CD4, and CD14 by flow cytometry is associated
      with NPM1 and FLT3 mutation status in cytogenetically normal acute myeloid
      leukemia.
AB  - In 83 patients with cytogenetically normal acute myeloid leukemia (CN-AML), those
      with NPM1 and wild-type FLT3 (FLT3-wt) mutation and their poor prognostic
      combination had distinctive flow cytometric findings: CN-AML with a mutation of
      NPM1 (NPMI-Mt) were CD34(-), CD14(-), and CD2pos and CD4; those with FLT3
      internal tandem duplications (ITD) were CD56pos, those with NPM1-Mt and FLT3-wt
      were CD34(-) and CD56(-); and those with poor prognostic combination NPM1-wt and
      FLT3-ITD were CD34pos and TdTpos. METHODS: We retrospectively correlated NPM1 and
      FLT3 mutation status with flow cytometric profile of leukemic blasts in 83 adult
      patients with cytogenetically normal acute myeloid leukemia (CN-AML). RESULTS:
      Mutation of the NPM1 gene (NPM1.mt) was found in 39 (47%) of 83 patients, and
      internal tandem duplication (ITD) of the FLT3 gene (FLT3-ITD) was seen in 38
      (46%) of 83 patients. Patients with CN-AML and with NPM1.mt were less likely to
      express CD34 (33% vs. 93%; 2P = .0001), CD2 (0% vs. 14%; 2P = .0187), and CD14
      (6% vs. 22%, 2P = .0476), and were more likely to express CD4 (65.5% vs. 37%; 2P
      = .0367) and CD19 (49% vs. 27%; 2P = .0506). The patients with CN-AML and with
      FLT3-ITD were more likely to express CD56 (47% vs. 23%; 2P = .0393). Moreover,
      patients with favorable prognostic combination of NPM1.mt and wild-type (wt) FLT3
      (n = 18) were less likely to express CD34 (33% vs. 74% all others; 2P = .0021)
      and CD56 (6% vs. 37% all others; 2P = .0072). The group with an unfavorable
      prognostic combination of NPM1-wt and FLT3-ITD (n = 17) were more likely to
      express CD34 (88% vs. 45% all others; 2P = .0011) and TdT (40% vs. 2% all others;
      2P = .0054). CONCLUSIONS: In patients with CN-AML, characteristic flow cytometric
      profile is associated with NPM1 and FLT3 mutation status.

PMID- 22481023
TI  - Complete valvular heart apparatus model from 4D cardiac CT.
AB  - The cardiac valvular apparatus, composed of the aortic, mitral, pulmonary and
      tricuspid valves, is an essential part of the anatomical, functional and
      hemodynamic characteristics of the heart and the cardiovascular system as a
      whole. Valvular heart diseases often involve multiple dysfunctions and require
      joint assessment and therapy of the valves. In this paper, we propose a complete
      and modular patient-specific model of the cardiac valvular apparatus estimated
      from 4D cardiac CT data. A new constrained Multi-linear Shape Model (cMSM),
      conditioned by anatomical measurements, is introduced to represent the complex
      spatio-temporal variation of the heart valves. The cMSM is exploited within a
      learning-based framework to efficiently estimate the patient-specific valve
      parameters from cine images. Experiments on 64 4D cardiac CT studies demonstrate
      the performance and clinical potential of the proposed method. Our method enables
      automatic quantitative evaluation of the complete valvular apparatus based on non
      invasive imaging techniques. In conjunction with existent patient-specific
      chamber models, the presented valvular model enables personalized computation
      modeling and realistic simulation of the entire cardiac system.

PMID- 22481025
TI  - A honeycomb lattice model simulating the surface states of topological
      insulators.
AB  - A honeycomb lattice model exhibiting the quantum spin-Hall effect is proposed,
      where the low-energy properties of the electrons are mainly determined by the
      energy spectrum in the vicinity of the Gamma point, for suitable parameters. The
      nontrivial topology of the energy bands is revealed by calculating the Chern
      numbers, Berry curvature distribution, and edge state spectrum. We further show
      that in the continuum limit, the model Hamiltonian is equivalent to the effective
      model for the surface states in thin films of three-dimensional topological
      insulators. As a consequence, this lattice model provides a useful tool for
      numerical simulation of the physical properties of the surface states.

PMID- 22481024
TI  - Generation of a mouse scFv library specific for porcine aminopeptidase N using
      the T7 phage display system.
AB  - Porcine aminopeptidase N (pAPN) is a common cellular receptor for swine
      transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus
      (PEDV). To investigate single-chain fragment variable (scFv) repertoire against
      pAPN, the genes encoding the immunoglobulin light chain variable region (VL) and
      heavy chain variable region (VH) were amplified by reverse transcript polymerase
      chain reaction (RT-PCR) using a series of degenerate primers from the spleen of
      BABL/c mice immunized with native pAPN. The VL and VH amplicons were combined
      randomly by a 12 amino acid flexible linker by splicing by overlap extension PCR
      (SOE-PCR), which produced the scFv gene repertoire. After ligation of the scFv
      gene repertoire into the T7Select10-3b vector, a mouse scFv phage library
      specific for pAPN was produced through in vitro packaging. The primary scFv
      library against pAPN contained 2.0*10(7) recombinant phage clones, and the titer
      of the amplified library was 3.6*10(9)pfu/mL. BstNI restriction analysis and DNA
      sequencing revealed that 28 phage clones from the primary pAPN scFv library
      showed excellent diversity. The effectiveness of the scFv library against pAPN
      was verified further by phage ELISA using the recombinant protein of the pAPN C
      subunit as coating antigen. The construction and evaluation of a murine scFv
      library against the common receptor pAPN of porcine coronaviruses TGEV and PEDV
      using the T7 phage display system are described.

PMID- 22481026
TI  - Long-term CFTR inhibition modulates 15d-prostaglandin J2 in human pulmonary
      cells.
AB  - Prostaglandins, the products of arachidonic acid release and oxidation by
      phospholipase A(2) and cyclooxygenases (COX) 1 and 2 respectively, are known as
      important inflammation mediators. However, their diversity in structure,
      properties and cell specificity make their physiological function difficult to
      define. In the lung, the prostaglandin D(2) (PGD(2)) metabolite 15d-PGJ(2) is
      known to modulate the properties of a large number of intracellular compounds,
      leading to both pro- and anti-inflammatory effects. In the lung, the serous sub
      mucosal glands, that strongly express CFTR (cystic fibrosis transmembrane
      conductance regulator), play an important role in the defence against
      inflammation, and their derivatives Calu-3 cells are largely used in in vitro
      experiments. The present study was undertaken to determine whether the PGD
      synthase-PGD(2)-15d-PGJ(2) pathway is active in Calu-3 cells, and whether its
      activity requires a functional CFTR. Both cellular and released PGD(2) and 15d
      PGJ(2) were measured in cells treated with CFTR inhibitors and stimulated or not
      with inflammatory IL-1beta. Pretreatment with either CFTR(inh172) or GlyH101
      inhibitors decreased the basal cell content of both prostaglandins, and so did
      acute stimulation with IL-1beta, but the latter was dramatically reversed in
      CFTR(inh172)-treated cells. CFTR(inh172) also altered the release of inflammation
      mediators PGE(2) and IL-8, and this effect was blunted by exogenous 15d-PGJ(2).
      CFTR(inh172)-induced modulation of 15d-PGJ(2) cellular content was not detected
      in CFTR-silenced Calu-3 cells, but it was reproduced in pulmonary CFBE41o-cells,
      which express F508del-CFTR. These results show that cellular 15d-PGJ(2)
      production, which controls PGE(2) and IL-8 release, is disturbed by CFTR
      dysfunction. In Calu-3 cells, 15d-PGJ(2) production resulted from COX-2-regulated
      COX-1 activation, while CFTR(inh172)-induced alteration of 15d-PGJ(2) synthesis
      involved both decreased expression of PGD synthase and disturbed relationships
      between both COXs. CFTR-mediated regulation of PGD synthase-PGD(2)-15d-PGJ(2)
      pathway and cellular 15d-PGJ(2) effects may involve a large number of molecular
      reactive pathways. Their exploration should help understand the development of CF
      inflammation and might bring new perspectives in its treatment.

PMID- 22481027
TI  - Metabolic effects of vitamin D active metabolites in monolayer and micromass
      cultures of nucleus pulposus and annulus fibrosus cells isolated from human
      intervertebral disc.
AB  - Intragenic polymorphisms in the vitamin D receptor gene are linked to disc
      degeneration features, suggesting that alterations in the vitamer-mediated
      signalling could be involved in the pathophysiology of the disc and that
      interaction of disc cells with vitamin D metabolites may be critical for disc
      health. The vitamer-mediated modulation of disc cells proliferation, metabolic
      activity, extracellular matrix (ECM) genes expression and proteins production was
      investigated. It was stated that disc cells express vitamin D receptor and are
      very sensitive to metabolic stimuli. In monolayer cultures, 1,25(OH)(2)D(3), but
      not 24,25(OH)(2)D(3), determined an inhibition of the proliferation and regulated
      also the ECM genes expression in nucleus pulposus and annulus fibrosus cells.
      Micromass cultures induced a more physiologic expression pattern of extracellular
      matrix genes. Cells Treatment with vitamin D metabolites did not result in
      relevant modifications of glycosaminoglycans production, except for annulus
      cells, whose production was reduced after 1,25(OH)(2)D(3) treatment. Moreover, a
      reduced glycosaminoglycans staining in both cell types and a significant reduced
      aggrecan gene expression in annulus cells treated with 1,25(OH)(2)D(3) were
      observed. A reduction of collagen I and II staining in annulus cells
      1,25(OH)(2)D(3) treated, in accordance with a downregulation of collagen genes
      expression, was also registered. Finally, the vitamin D receptor gene expression
      did not show significant metabolite-mediated modification in monolayer or
      micromass cultures. These findings could enhance new insights on the biochemical
      mechanisms regulated by vitamin D in disc cartilage and possibly involved in the
      development of physiological/pathological modifications of the disc.

PMID- 22481028
TI  - [Very small intracranial aneurysms: Clip or coil].
AB  - INTRODUCTION: It is not unusual for very small aneurysms (<=3mm) to be
      responsible for subarachnoid haemorrhage. In addition, modern imaging has
      increased diagnosis of those that are asymptomatic. Because of their spatial
      configuration and thin and fragile walls, very small aneurysms can be a sizeable
      challenge for both open surgical and endovascular treatment. Based on recent
      literature data, the present manuscript reviews treatment indications and the
      choice of treatment strategy to occlude these particular aneurysms. METHODS:
      Literature review concerning surgical and endovascular treatment of very small
      aneurysms (<=3mm). Arterial dissections and blister aneurysms were excluded.
      RESULTS: We found no study that systematically and specifically assessed surgical
      treatment of very small aneurysms. Investigations of endovascular treatment are
      almost exclusively retrospective, usually evaluating a small number of patients,
      and are limited by selection bias. Despite often contradictory results, it
      appears that very small aneurysms carry a higher risk of rupture during
      endovascular procedures and higher ensuing mortality, as compared to larger
      aneurysms. The use of more flexible coils and additional endovascular tools
      appears to reduce this risk. There is no study comparing surgical to endovascular
      treatment. CONCLUSION: Very small aneurysms carry higher treatment risks than
      larger aneurysms. A prospective randomised trial is justified for those very
      small aneurysms for which treatment is indicated.

PMID- 22481029
TI  - Ruptured aneurysms and the International Subarachnoid Aneurysm Trial (ISAT): What
      is known and what remains to be questioned.
AB  - BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT) was
      a major study comparing clipping and coiling of ruptured intracranial aneurysms.
      The trial provided answers that were the subject of multiple letters and
      editorial comments. METHODS: We review the most common critiques that were
      published in major neurosurgical journals, trying to identify what aspects of
      ISAT could have been improved, and what questions remain to be studied. RESULTS:
      Frequent critiques include imprecise selection criteria, lack of requirement for
      the technical proficiency of surgical participants, lack of angiographic controls
      of surgically treated patients, and poorly chosen primary endpoints. Other issues
      that are often raised are the poor recruitment rate which endangered
      generalization of results, the excessive delays in performing clipping which led
      to rebleeding episodes, lack of blinding in the assessment of outcomes, and
      subjective questionnaires. Nonetheless, the design of the study as a pragmatic
      trial was appropriate, as was the choice of the primary endpoint. The overall
      trial results could not be verified for all subgroups of interest, and currently
      many patients who would not have been included in ISAT are treated by coiling,
      while other patients are treated by clipping despite ISAT results. Hence a new
      trial, complementary to the original ISAT, may now be indicated. CONCLUSION: ISAT
      was well-designed and conducted, but many questions remain. They should be
      addressed by a new trial.

PMID- 22481030
TI  - Suitability of cerebral aneurysms for endovascular treatment: Evolution of
      criteria with technological developments.
AB  - With the introduction of electrically detachable coils in 1991 and later the
      results of the ISAT trial in 2002, endovascular approach became the primary
      treatment for cerebral aneurysms in many countries. The suboptimal quality of
      anatomical results and the relatively high rate of aneurysm recurrence after
      treatment still hamper an even more widespread of the technique. In this paper,
      we will make a review of the anatomical factors associated with poor anatomical
      results as well as technological developments aiming at improvement of aneurysm
      healing.

PMID- 22481032
TI  - Management of patients with aneurismal subarachnoid hemorrhage and associated
      symptomatic vasospasm on presentation.
AB  - Rebleeding and symptomatic vasospasm (VS) are the major causes of subsequent
      morbidity and mortality in patients surviving a subarachnoid hemorrhage (SAH).
      Although most patients present rapidly after the bleed, some may seek medical
      attention in a delayed fashion due to non-resolving or worsening headaches or new
      neurological deficits, requiring treatment during the period at risk for VS. Such
      patients may either present asymptomatic radiological VS on their diagnostic
      angiogram or present symptomatic VS confirmed on angiogram. A similar situation
      may occur in patients presenting within the first 48 hours after SAH with very
      early angiographic VS. Deciding on the optimal timing and modality of treatment
      in such patients with SAH and symptomatic VS on presentation is controversial.
      Only six observational studies that specifically assessed aneurysm treatment in
      the presence of symptomatic VS have been published to date. We reviewed the
      published literature on the management of ruptured intracranial aneurysms in the
      presence of symptomatic VS and suggest avenues for future studies.

PMID- 22481033
TI  - Blister-like aneurysms of the internal carotid artery - management
      considerations.
AB  - Blood blister-like aneurysms (BBA) originate at non-branching sites of the
      internal carotid artery (ICA). These aneurysms present a fragile wall and a
      poorly defined broad-based neck. Recognition of the BBA is essential for proper
      management of these vascular lesions. Various surgical and endovascular
      strategies have been attempted for these heterogeneous lesions. These have been
      associated with significant morbidity and mortality including rebleeding,
      regrowth, ischemic and thromboembolic complications. The authors review the key
      elements important for diagnosis and management of BBA and review current
      treatment options.

PMID- 22481035
TI  - Reversal of Klein reflection by magnetic barriers in bilayer graphene.
AB  - Massless Dirac fermions in monolayer graphene exhibit total transmission when
      normally incident on a scalar potential barrier, a consequence of the Klein
      paradox originally predicted by O Klein for relativistic electrons obeying the 3
      + 1 dimensional Dirac equation. For bilayer graphene, charge carriers are massive
      Dirac fermions and, due to different chiralities, electron and hole states are
      not coupled to each other. Therefore, the wavefunction of an incident particle
      decays inside a barrier as for the non-relativistic Schrodinger equation. This
      leads to exponentially small transmission upon normal incidence. We show that, in
      the presence of magnetic barriers, such massive Dirac fermions can have
      transmission even at normal incidence. The general consequences of this behavior
      for multilayer graphene consisting of massless and massive modes are mentioned.
      We also briefly discuss the effect of a bias voltage on such magnetotransport.

PMID- 22481034
TI  - Can tissue-based immune markers be used for studying the natural history of
      cancer?

PMID- 22481037
TI  - The relationship of coping behaviors to depressive symptoms in youth with
      epilepsy: an examination of caregiver and youth proxy report.
AB  - Study aims were to explore evaluation and comparison of measures of coping and
      the relationship of epilepsy-specific coping responses to depressive symptoms in
      youth with epilepsy (YWE). Seventy-six YWE ages 9-17 completed the Children's
      Depression Inventory (CDI) and the Kidcope. Sixty-six caregivers reported on
      youth coping (CHIC) and seizure activity. Epilepsy variables were abstracted from
      electronic medical records. There were no significant correlations between the
      CHIC coping factors and individual Kidcope scores. Only one CHIC factor,
      "competence/optimism," was significantly negatively correlated with CDI.
      Regression analyses revealed a significant association between CDI and negative
      coping (Kidcope) after adjusting for sex, number of AEDs, and seizure severity.
      On the CDI, 27% of YWE endorsed suicidal ideation. Findings provide preliminary
      support for use of the Kidcope as a measure of negative epilepsy-specific coping.
      These results imply that youth coping and suicidal ideation are important to
      assess in relation to depressive symptoms and that youth report of these symptoms
      is particularly salient to the evaluation of youth functioning.

PMID- 22481038
TI  - Patient knowledge about issues related to pregnancy in epilepsy: a cross
      sectional study.
AB  - In 2009, new guidelines were established by the American Academy of Neurology
      regarding pregnancy in women with epilepsy. A questionnaire was developed to
      assess patient knowledge of current guidelines related to epilepsy and pregnancy.
      Patients were recruited from a single outpatient clinic in a large Canadian
      tertiary care center. Patients were eligible to participate if they were female,
      of reproductive age, had active epilepsy for at least 6 months and were not
      cognitively impaired. One hundred women completed the survey (response rate 87%)
      with a median score of 40%. A significant association was found between total
      score and years of education (p<0.001). Significant associations were not found
      between total score and epilepsy duration (p=0.37), previously being pregnant
      (p=0.22), and polytherapy (p=0.31). Patient knowledge of the impact of epilepsy
      on pregnancy is low. More knowledge translation efforts are required to increase
      knowledge of issues related to pregnancy for women with epilepsy.

PMID- 22481039
TI  - Phenytoin is dead, long live phenytoin?

PMID- 22481040
TI  - Newer antiepileptic drugs in the treatment of status epilepticus: impact on
      prognosis.
AB  - Newer antiepileptic drugs (AEDs) are increasingly prescribed and seem to have a
      comparable efficacy as the classical AEDs; however, their impact on status
      epilepticus (SE) prognosis has received little attention. In our prospective SE
      database (2006-2010), we assessed the use of older versus newer AEDs
      (levetiracetam, pregabalin, topiramate, lacosamide) over time and its
      relationship to outcome (return to clinical baseline conditions, new handicap, or
      death). Newer AEDs were used more often toward the end of the study period (42%
      of episodes versus 30%). After adjustment for SE etiology, SE severity score, and
      number of compounds needed to terminate SE, newer AEDs were independently related
      to a reduced likelihood of return to baseline (p<0.001) but not to increased
      mortality. These findings seem in line with recent findings on refractory
      epilepsy. Also, in view of the higher price of the newer AEDs, well-designed,
      prospective assessments analyzing the impact of newer AEDs on efficacy and
      tolerability in patients with SE appear mandatory.

PMID- 22481041
TI  - Energy drinks and seizures: what is the link?

PMID- 22481042
TI  - Topiramate and its effect on fMRI of language in patients with right or left
      temporal lobe epilepsy.
AB  - Topiramate (TPM) is well recognized for its negative effects on cognition,
      language performance and lateralization results on the intracarotid amobarbital
      procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and
      the fMRI signals are less clear. Functional MRI is increasingly used for
      presurgical evaluation of epilepsy patients in place of IAP for language
      lateralization. Thus, the goal of this study was to assess the effects of TPM on
      fMRI signals. In this study, we included 8 patients with right temporal lobe
      epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM).
      Matched to them for age, handedness and side of seizure onset were 8 patients
      with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness
      to the patients with TLE were 32 healthy controls. The fMRI paradigm involved
      semantic decision/tone decision task (in-scanner behavioral data were collected).
      All epilepsy patients received a standard neuropsychological language battery.
      One sample t-tests were performed within each group to assess task-specific
      activations. Functional MRI data random-effects analysis was performed to
      determine significant group activation differences and to assess the effect of
      TPM dose on task activation. Direct group comparisons of fMRI, language and
      demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of
      the effects of TPM on blood oxygenation level-dependent (BOLD) signal were
      performed. Groups were matched for age, handedness and, within the R/L TLE
      groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose.
      The in-scanner language performance of patients was worse when compared to
      healthy controls - all p<0.044. While all groups showed fMRI activation typical
      for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed
      significant fMRI signal differences between groups (increases in left cingulate
      gyrus and decreases in left superior temporal gyrus in the patients with LTLE
      +TPM; increases in the right BA 10 and left visual cortex and decreases in the
      left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with
      activation in the basal ganglia and negative associations with activation in
      anterior cingulate and posterior visual cortex. Thus, TPM appears to have a
      different effect on fMRI language distribution in patients with R/L TLE and a
      dose-dependent effect on fMRI signals. These findings may, in part, explain the
      negative effects of TPM on cognition and language performance and support the
      notion that TPM may affect the results of language fMRI
      lateralization/localization.

PMID- 22481043
TI  - Development and validation of the Kilifi Stigma Scale for Epilepsy in Kenya.
AB  - The aim of this study was to develop and validate a tool to measure perceived
      stigma among people with epilepsy (PWE) in Kilifi, Kenya. We reviewed existing
      scales that measured stigma, particularly of epilepsy. We conducted a qualitative
      study to determine salient concerns related to stigma in Kilifi. Themes were
      generated, and those related to stigma were used to construct an 18-item stigma
      scale. A descriptive cross-sectional survey was then conducted among 673 PWE to
      assess the reliability and validity of the scale. Internal consistency was
      calculated using Cronbach's alpha and test-retest reliability with an interclass
      correlation coefficient. The final scale had 15 items, which had high internal
      consistency (Cronbach's alpha=0.91) and excellent test-retest reliability
      (r=0.92). Factor analysis indicated that the scale was unidimensional with one
      factor solution explaining 45.8% of the variance. The Kilifi Stigma Scale for
      Epilepsy is a culturally appropriate measure of stigma with strong psychometric
      properties.

PMID- 22481044
TI  - Confeito-like assembly of organosilicate-caged fluorophores: ultrabright
      suprananoparticles for fluorescence imaging.
AB  - We report ultrabright, photostable, sub-25 nm nanoparticle agglomerates
      (suprananoparticles) assembled from a few hundred 3.3 +/- 0.9 nm units, each
      hosting on average a single rhodamine 6G (Rh6G) dye molecule encased in a thin
      organosilicate cage. These individual Rh6G-doped nanoparticle (DOSNP) units
      consist of a hydrophobic core containing the dye and an ultrathin, conformal
      silicate shell modified by CO(2) plasma to confer a beneficial 'cage effect' as
      well as surface hydrophilicity. The isolation of the dye within individual DOSNP
      units in the final 22 +/- 5 nm agglomerate avoids dimerization and related
      spontaneous molecular interactions that otherwise lead to self-quenching in
      closely co-localized fluorophores. The resulting suprananoparticles are over 200
      times brighter than the free Rh6G molecules in the same volume. There is no
      observable dye leaching, and the labels are 20-fold more resistant to
      photobleaching than free Rh6G in solution. We demonstrate the attractive features
      of DOSNPs as labels in bioimaging applications.

PMID- 22481045
TI  - Letter to the editor regarding Kawada's comments on the paper labour force
      participation and the influence of having CVD on income poverty of older workers.

PMID- 22481046
TI  - Impact of intravascular ultrasound guidance in routine percutaneous coronary
      intervention for conventional lesions: data from the EXCELLENT trial.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) offers tomographic images of coronary
      artery, helping physicians refine percutaneous coronary intervention (PCI)
      procedures. However, it is still controversial whether routine use of IVUS in
      conventional lesions leads to improvement in clinical outcomes after PCI.
      METHODS: From the EXCELLENT trial, patients were grouped into IVUS-guided versus
      IVUS-non-guided PCI (619 and 802 patients, respectively). The crude patients as
      well as the propensity score matched pairs were compared with regard to clinical
      outcomes. RESULTS: Baseline characteristics showed younger age and lower
      incidence of comorbidities in the IVUS group. IVUS-guided PCI was associated with
      more aggressive treatment such as longer stenting length, larger stent diameter,
      and greater number of stents implanted. In the total population, IVUS guidance
      was associated with a significantly higher risk of periprocedural MI with no
      significant differences in other outcomes. In the matched cohort (463 matched
      pairs, 926 patients), IVUS guidance was associated with significantly increased
      risk of target lesion failure (4.3% vs. 2.4%; p=0.047 by conditional logistic
      regression) and major adverse cardiovascular events at 1 year almost exclusively
      due to increased risk of periprocedural myocardial infarction (MI) (1.6% vs.
      0.2%; p=0.050), while the rates of cardiac death, spontaneous MI, and target
      lesion revascularization did not differ significantly between the two groups.
      CONCLUSIONS: The adjunctive use of IVUS during PCI was associated with more
      stents implanted, longer stenting, and bigger stenting. There were no significant
      advantages of IVUS guidance, but rather a significant increase in periprocedural
      enzyme elevation, reflecting more aggressive procedures performed with IVUS
      guidance.

PMID- 22481047
TI  - Impact of culprit plaque volume and composition on myocardial microcirculation
      following primary angioplasty in patients with ST-segment elevation myocardial
      infarction: virtual histology intravascular ultrasound analysis.
AB  - BACKGROUND: An impaired myocardial perfusion state after primary angioplasty is a
      strong predictor of long-term adverse outcomes in patients with STEMI. We
      assessed the relationship between culprit plaque characteristics and myocardial
      perfusion state after primary angioplasty in patients with ST-segment elevation
      myocardial infarction (STEMI). METHODS: A total of 101 consecutive patients with
      de novo STEMI were divided into 3 groups according to the state of myocardial
      perfusion assessed by ST-segment elevation resolution (STR): Group A (complete:
      STR >= 70%, n=26), Group B (partial: STR<70% but >= 30%, n=55) and Group C (none:
      STR<30%, n=20). We analyzed plaque features by virtual histology intravascular
      ultrasound (VH-IVUS) and assessed the relationship between culprit plaque
      characteristics and STR after primary angioplasty. RESULTS: Total plaque volume
      was significantly higher in Group C than in Groups A and B (146.4 +/- 38.0
      mm(3)vs. 93.3 +/- 29.1 mm(3) and 105.8 +/- 31.5 mm(3), p<0.001, respectively).
      Necrotic core (NC) volume was also significantly higher in Group C than in Groups
      A and B (25.4 +/- 8.0m m(3), vs. 11.9 +/- 6.3 mm(3) and 17.3 +/- 9.7 mm(3),
      p<0.001, respectively). Analysis of receiver-operating characteristic curves
      revealed that total plaque volume and NC volume had the best diagnostic accuracy
      of all the VH-IVUS parameters to predict STR<30%. The optimal cutoff values
      (sensitivity/specificity) were 123.4 mm(3) (75.0%/75.3%) for total plaque volume
      and 20.3mm(3) (75.0%/74.1%) for NC volume. CONCLUSIONS: Culprit plaque with large
      plaque burden and high NC volume is closely associated with poor STR after
      revascularization.

PMID- 22481048
TI  - Inhibition of cardiomyocyte lysosomal activity in hydroxychloroquine
      cardiomyopathy.

PMID- 22481049
TI  - Targeting anti-smoking messages: does audience race matter?
AB  - This study examined whether an adolescent's self-identified race moderates the
      perceived effectiveness of anti-smoking messages. A sample of 94 never smoking
      adolescents (59% African-American; 41% European-American) participated in this
      two-part study. First, they rated the persuasive strength of a series of five
      decontextualized anti-smoking messages (i.e., messages delivered in text format).
      Second, they were exposed to five sets of anti-smoking public service
      announcements (PSAs; viewed as TV advertisements) that had embedded in them the
      five anti-smoking messages used in the first part of the study and rated their
      smoking refusal self-efficacy after each one. Although race moderated
      participants' ratings of the decontextualized messages, there were no significant
      moderating effects of race when those messages were embedded in PSAs. The results
      of this study support the notion that anti-smoking PSAs should not be targeted to
      adolescent racial background, but suggests that decontextualized anti-smoking
      messages may be more effective if targeted to adolescent race.

PMID- 22481051
TI  - Analytic cognitive style predicts religious and paranormal belief.
AB  - An analytic cognitive style denotes a propensity to set aside highly salient
      intuitions when engaging in problem solving. We assess the hypothesis that an
      analytic cognitive style is associated with a history of questioning, altering,
      and rejecting (i.e., unbelieving) supernatural claims, both religious and
      paranormal. In two studies, we examined associations of God beliefs, religious
      engagement (attendance at religious services, praying, etc.), conventional
      religious beliefs (heaven, miracles, etc.) and paranormal beliefs (extrasensory
      perception, levitation, etc.) with performance measures of cognitive ability and
      analytic cognitive style. An analytic cognitive style negatively predicted both
      religious and paranormal beliefs when controlling for cognitive ability as well
      as religious engagement, sex, age, political ideology, and education.
      Participants more willing to engage in analytic reasoning were less likely to
      endorse supernatural beliefs. Further, an association between analytic cognitive
      style and religious engagement was mediated by religious beliefs, suggesting that
      an analytic cognitive style negatively affects religious engagement via lower
      acceptance of conventional religious beliefs. Results for types of God belief
      indicate that the association between an analytic cognitive style and God beliefs
      is more nuanced than mere acceptance and rejection, but also includes adopting
      less conventional God beliefs, such as Pantheism or Deism. Our data are
      consistent with the idea that two people who share the same cognitive ability,
      education, political ideology, sex, age and level of religious engagement can
      acquire very different sets of beliefs about the world if they differ in their
      propensity to think analytically.

PMID- 22481050
TI  - Genetic influences on craving for alcohol.
AB  - INTRODUCTION: Craving is being considered for inclusion in the Diagnostic and
      Statistical Manual (DSM) DSM-5. However, little is known of its genetic
      underpinnings - specifically, whether genetic influences on craving are distinct
      from those influencing DSM-IV alcohol dependence. METHOD: Analyses were conducted
      in a sample of unrelated adults ascertained for alcohol dependence (N=3976).
      Factor analysis was performed to examine how alcohol craving loaded with the
      existing DSM-IV alcohol dependence criteria. For genetic analyses, we first
      examined whether genes in the dopamine pathway, including dopamine receptor genes
      (DRD1, DRD2, DRD3, DRD4) and the dopamine transporter gene (SLC6A3), which have
      been implicated in neurobiological studies of craving, as well as alpha-synuclein
      (SNCA), which has been previously found to be associated with craving, were
      associated with alcohol craving in this sample. Second, in an effort to identify
      novel genetic variants associated with craving, we conducted a genomewide
      association study (GWAS). For variants that were implicated in the primary
      analysis of craving, we conducted additional comparisons - to determine if these
      variants were uniquely associated with alcohol craving as compared with alcohol
      dependence. We contrasted our results to those obtained for DSM-IV alcohol
      dependence, and also compared alcohol dependent individuals without craving to
      non-dependent individuals who also did not crave alcohol. RESULTS: Twenty-one
      percent of the full sample reported craving alcohol. Of those reporting craving,
      97.3% met criteria for DSM-IV alcohol dependence with 48% endorsing all 7
      dependence criteria. Factor analysis found a high factor loading (0.89) for
      alcohol craving. When examining genes in the dopamine pathway, single nucleotide
      polymorphisms (SNPs) in DRD3 and SNCA were associated with craving (p<0.05).
      There was evidence for association of these SNPs with DSM-IV alcohol dependence
      (p<0.05) but less evidence for dependence without craving (p>0.05), suggesting
      that the association was due in part to craving. In the GWAS, the greatest
      evidence of association with craving was for a SNP in the integrin alpha D
      (ITGAD) gene on chromosome 7 (rs2454908; p=1.8*10(-6)). The corresponding p-value
      for this SNP with DSM-IV alcohol dependence was similar (p=4.0*10(-5)) but was
      far less with dependence without craving (p=0.02), again suggesting the
      association was due to alcohol craving. Adjusting for dependence severity (number
      of endorsed criteria) attenuated p-values but did not eliminate association.
      CONCLUSIONS: Craving is frequently reported by those who report multiple other
      alcohol dependence symptoms. We found that genes providing evidence of
      association with craving were also associated with alcohol dependence; however,
      these same SNPs were not associated with alcohol dependence in the absence of
      alcohol craving. These results suggest that there may be unique genetic factors
      affecting craving among those with alcohol dependence.

PMID- 22481052
TI  - Impact of wind turbine sound on annoyance, self-reported sleep disturbance and
      psychological distress.
AB  - PURPOSE OF THE RESEARCH: The present government in the Netherlands intends to
      realize a substantial growth of wind energy before 2020, both onshore and
      offshore. Wind turbines, when positioned in the neighborhood of residents may
      cause visual annoyance and noise annoyance. Studies on other environmental sound
      sources, such as railway, road traffic, industry and aircraft noise show that
      (long-term) exposure to sound can have negative effects other than annoyance from
      noise. This study aims to elucidate the relation between exposure to the sound of
      wind turbines and annoyance, self-reported sleep disturbance and psychological
      distress of people that live in their vicinity. Data were gathered by
      questionnaire that was sent by mail to a representative sample of residents of
      the Netherlands living in the vicinity of wind turbines PRINCIPAL RESULTS: A dose
      response relationship was found between immission levels of wind turbine sound
      and selfreported noise annoyance. Sound exposure was also related to sleep
      disturbance and psychological distress among those who reported that they could
      hear the sound, however not directly but with noise annoyance acting as a
      mediator. Respondents living in areas with other background sounds were less
      affected than respondents in quiet areas. MAJOR CONCLUSIONS: People living in the
      vicinity of wind turbines are at risk of being annoyed by the noise, an adverse
      effect in itself. Noise annoyance in turn could lead to sleep disturbance and
      psychological distress. No direct effects of wind turbine noise on sleep
      disturbance or psychological stress has been demonstrated, which means that
      residents, who do not hear the sound, or do not feel disturbed, are not adversely
      affected.

PMID- 22481053
TI  - Selection of flight feathers from Buteo buteo and Accipiter gentilis for use in
      biomonitoring heavy metal contamination.
AB  - The concentrations of Hg were determined in all primary flight feathers from 20
      specimens of Buteo buteo and 49 specimens of Accipiter gentilis, which had died
      in various Wildlife Recovery Centres in Galicia (NW Spain) between 2001 and 2009.
      The aim of the study was to standardize the feather or feathers that should be
      analyzed in each species to enable inter-individual comparison of the levels of
      contamination, taking into consideration any variability in the concentrations of
      Hg caused by the birds' molting patterns. For both species the results show a
      high degree of both inter (e.g. an individual of A. gentilis showed 426 ng g(-1)
      of Hg as median and 568 ng g(-1) as median absolute deviation, MAD) and intra
      individual variability (e.g. primary feather number seven - P7 - of all the A.
      gentilis individuals showed 537 ng g(-1) of Hg as median and 1129 ng g(-1) as
      MAD). Although molting did not have a clear effect on the concentrations of Hg in
      the flight feathers, it was possible to identify the most representative feather
      in each individual, taking into account the amount of metal excreted in each
      feather and the intra-individual variability. For B. buteo use of flight feather
      P6 is recommended for Hg biomonitoring studies; the amount of Hg excreted to this
      feather was 509 ng as median, which represents the 14% (from 10 to 20%) of the
      total Hg present in all the primary feathers. For A. gentilis the recommended
      feather is P7, which has a median of 86 ng of Hg (corresponding to 12%, and
      varying between 5 and 22%).

PMID- 22481054
TI  - Spatiotemporal variability of submicrometer particle number size distributions in
      an air quality management district.
AB  - First measurements of ambient 10-1000 nm particle number concentrations (N(TOT))
      and size distributions were made at an urban, coastal, mountain and downwind site
      within the Central Taiwan Air Quality Management District during a cold and a
      warm period. The primary objectives were to characterize the spatial and temporal
      variability of the size-fractionated submicrometer particles and their
      relationships with copollutants and meteorological parameters. The results show
      that the ultrafine particles (<100 nm) are the major contributor to the N(TOT).
      The mean N(TOT) was highest at the urban site, whereas lower and comparable at
      the three other sites. Although the mean N(TOT) at each site showed insignificant
      differences between study periods, their diurnal patterns and size distribution
      modal characteristics were modestly to substantially different between study
      sites. Correlation analyses of time-resolved collocated aerosol, copollutants and
      meteorological data suggest that the observed variability is largely attributable
      to the local traffic and to a lesser extent photochemistry and SO(2) possibly
      from combustion sources or regional transport. Despite sharing a common traffic
      source, the ultrafine particles were poorly correlated with the accumulation
      particles (100-1000 nm), between which the latter showed strong positive
      correlation with the PM(2.5) and PM(10). Overall, the N(TOT) and size
      distributions show modest spatial heterogeneity and strong diurnal variability.
      In addition, the ultrafine particles have variable sources or meteorology
      dependent formation processes within the study area. The results imply that
      single-site measurements of PM(2.5), PM(10) or N(TOT) alone and without
      discriminating particle sizes would be inadequate for exposure and impact
      assessment of submicrometer particle numbers in a region of diverse environments.

PMID- 22481055
TI  - Assessing time-integrated dissolved concentrations and predicting toxicity of
      metals during diel cycling in streams.
AB  - Evaluating water quality and the health of aquatic organisms is challenging in
      systems with systematic diel (24 h) or less predictable runoff-induced changes in
      water composition. To advance our understanding of how to evaluate environmental
      health in these dynamic systems, field studies of diel cycling were conducted in
      two streams (Silver Bow Creek and High Ore Creek) affected by historical mining
      activities in southwestern Montana. A combination of sampling and modeling tools
      was used to assess the toxicity of metals in these systems. Diffusive Gradients
      in Thin Films (DGT) samplers were deployed at multiple time intervals during diel
      sampling to confirm that DGT integrates time-varying concentrations of dissolved
      metals. Site specific water compositions, including time-integrated dissolved
      metal concentrations determined from DGT, a competitive, multiple-toxicant biotic
      ligand model, and the Windemere Humic Aqueous Model Version 6.0 (WHAM VI) were
      used to determine the equilibrium speciation of dissolved metals and biotic
      ligands. The model results were combined with previously collected toxicity data
      on cutthroat trout to derive a relationship that predicts the relative
      survivability of these fish at a given site. This integrative approach may prove
      useful for assessing water quality and toxicity of metals to aquatic organisms in
      dynamic systems and evaluating whether potential changes in environmental health
      of aquatic systems are due to anthropogenic activities or natural variability.

PMID- 22481056
TI  - High clonal heterogeneity of Panton-Valentine leukocidin-positive meticillin
      resistant Staphylococcus aureus strains from skin and soft-tissue infections in
      the Province of Bolzano, Northern Italy.
AB  - Panton-Valentine leukocidin (PVL)-positive community-associated meticillin
      resistant Staphylococcus aureus (CA-MRSA) isolates are widespread in many
      countries, with varying distribution and epidemiology. The aim of this study was
      to characterise 10 PVL-positive MRSA isolates collected during February 2010 to
      January 2011 from skin and soft-tissue infections in the North Italian Province
      of Bolzano. Accessory gene regulator (agr) typing, staphylococcal cassette
      chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene typing,
      multilocus sequence typing, toxin gene profiling, polymerase chain reaction for
      type I arginine catabolic mobile element (ACME) and antimicrobial resistance
      typing were applied to the isolates. Eight different CA-MRSA clones were
      identified, including ST30-IVc, ST772-V, ST80-IVc, ST5-IVc, ST88-IVa, ST93-IVa,
      ST8-IVc and the type I ACME-positive ST8-IVa. The high heterogeneity of PVL
      positive MRSA probably reflects the introduction of different clones by
      international travellers or immigrants.

PMID- 22481057
TI  - Posaconazole plasma concentrations and invasive mould infections in patients with
      haematological malignancies.
AB  - Posaconazole (PCZ) is a triazole antifungal agent that has broad activity against
      pathogenic fungi and is increasingly used for prophylaxis and treatment of
      invasive mould infections (IMIs). PCZ is only available as an oral formulation,
      with varying absorption from the gastrointestinal tract. However, reports
      correlating PCZ plasma concentrations (PPCs) with breakthrough IMIs are rare. In
      this study, PPCs were analysed in a prospective, observational, single-centre
      study and the correlation of PPCs with breakthrough IMIs in patients with
      haematological malignancies was evaluated. Risk factors associated with low PPCs
      were further evaluated. A total of 109 PPCs were measured in 34 cases receiving
      PCZ prophylaxis (n=31) or treatment (n=3). Levels below the target of 0.5 MUg/mL
      were detected in 24 (71%) of the 34 cases; in 15 (63%) of these 24 cases
      concentrations were found to be <0.20 MUg/mL. Three patients receiving PCZ
      prophylaxis met the criteria of breakthrough infection. Notably, prior to
      development of IMI, PPCs were below the target in all three individuals.
      Associated risk factors for insufficient PPCs varied from previous reports. In
      conclusion, these data demonstrate that therapeutic drug monitoring of PCZ is
      mandatory in all patients with haematological malignancies as low PPCs are common
      and may be associated with development of IMIs.

PMID- 22481058
TI  - Role of IncHI2 plasmids harbouring blaVIM-1, blaCTX-M-9, aac(6')-Ib and qnrA
      genes in the spread of multiresistant Enterobacter cloacae and Klebsiella
      pneumoniae strains in different units at Hospital Vall d'Hebron, Barcelona,
      Spain.
AB  - Seven Enterobacter cloacae isolates and seven Klebsiella pneumoniae isolates
      harbouring a phenotype compatible with the production of a metallo-beta-lactamase
      were recovered between 2009 and 2011 in three Intensive Care Units of Hospital
      Vall d'Hebron (Barcelona, Spain). The presence of bla(VIM), bla(IMP), bla(NDM),
      bla(CTX-M), aac(6')-Ib, qnrA, qnrB and qnrS genes was screened by polymerase
      chain reaction (PCR) and sequencing. Clonal relatedness of the isolates was
      assessed by pulsed-field gel electrophoresis (PFGE) and, in the case of K.
      pneumoniae isolates, by multilocus sequence typing (MLST). PCR-based replicon
      typing, Southern hybridisation, plasmid double-locus sequence typing and MOB
      relaxase classification methods were used to identify and characterise the
      plasmids carrying the resistance genes. Transferability of the identified
      plasmids was tested by conjugation assays. All 14 isolates were found to carry
      bla(VIM-1), bla(CTX-M-9) (except one isolate), aac(6')-Ib and qnrA genes.
      Clonality assessment demonstrated that E. cloacae isolates were distributed in
      three clonal clusters, whereas all of the K. pneumoniae isolates belonged to one
      unique clone, identified as sequence type ST252. All studied isolates harboured a
      large conjugative IncHI2 MOB(H11) plasmid carrying all of the detected resistance
      genes. Plasmid DNA analysis showed that all of them belonged to the ST1 IncHI2
      plasmid cluster and shared the same relaxase partial sequence. In conclusion, the
      present study describes the dissemination within a hospital of multiresistant E.
      cloacae and K. pneumoniae isolates producing VIM-1. A complex clonal epidemiology
      of the E. cloacae isolates was observed and plasmid DNA analysis strongly
      supports horizontal exchanges of the same IncHI2 plasmid between different
      strains and species.

PMID- 22481059
TI  - Maculopathy in patient with systemic lupus erythematosus treated with
      hydroxychloroquine.
AB  - A 50-years-old woman with systemic lupus erythematosus treated for 13 years with
      hydroxychloroquine developed nephropathy and high blood pressure five years ago
      as well as moderate loss of vision in her right eye. Fundoscopy showed
      alterations of macular pigmentation only in the right eye. Visual fields 10-2
      were normal in both eyes. Optical coherence tomography showed hyperreflective
      foveal thickening with a hyporreflective cavity underlying in the right macula,
      and was normal in left macula. Fluorescein angiography showed no bulls-eye
      pattern, but did show microaneurysms in vascular arcades. Multifocal central
      electroretinogram was diminished in right eye and the electrorretinogram pattern
      was diminished in both eyes. We concluded that the alterations of the right eye
      were suggestive of ischemic maculopathy, not hydroxychloroquine toxicity.

PMID- 22481060
TI  - Evaluations of biomarkers associated with sensitivity to 5-fluorouracil and
      taxanes for recurrent/advanced breast cancer patients treated with capecitabine
      based first-line chemotherapy.
AB  - The aim of the present study was to investigate the gene expression of biomarkers
      associated with the sensitivity to fluoropyrimidine and taxanes in
      recurrent/advanced breast cancer patients treated with first-line capecitabine
      chemotherapy. We evaluated the clinicopathological/prognostic significance of
      thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine
      phosphorylase (TP), class III beta-tubulin (betaIII-tubulin), and stathmin-1 or
      oncoprotein-18 (STMN1). Formalin-fixed, paraffin-embedded tumor specimens from 42
      patients were used for analysis of TS, DPD, TP, betaIII-tubulin, and STMN1
      expression with a real-time reverse transcription-PCR technique. Patients were
      classified into the high-expression and low-expression groups according to the
      median value of the expression level of each biomarker. There was a significantly
      longer time to progression (TTP) in the high-TP group (P=0.018). The multivariate
      analysis revealed that the TP expression (hazard ratio for the low-TP group vs.
      the high-TP group, 2.873; 95% confidence interval, 1.143-7.223; P=0.025) is
      independent of prognostic factors for TTP. In the subgroup of patients treated
      with capecitabine plus taxanes as first-line chemotherapy, TTP was significantly
      longer in the low-betaIII-tubulin group (P=0.047). The gene expression of TS,
      DPD, and STMN1 failed to have any significant impact on the outcome. These
      results provide further evidence that the TP expression may be a prognostic
      factor in breast cancer patients treated with capecitabine-based first-line
      chemotherapy, and betaIII-tubulin can be used to predict the outcome of
      capecitabine in combination with taxanes as first-line chemotherapy. Therefore,
      these potential biomarkers should be further evaluated.

PMID- 22481061
TI  - A novel oral dosage formulation of the ginsenoside aglycone protopanaxadiol
      exhibits therapeutic activity against a hormone-insensitive model of prostate
      cancer.
AB  - This study focuses on determining the pharmacokinetics, biodistribution, and
      efficacy of the ginsenoside aglycone protopanaxadiol (aPPD) administered as a
      single agent in a novel oral dosage formulation. To obtain these data and to
      characterize the stability of aPPD, appropriate analytical assay development was
      carried out. The solubility and stability of aPPD were determined, and the
      compound was formulated for oral gavage. aPPD levels in blood and tissues
      following oral administration to nu/nu nude mice were determined using liquid
      chromatography-mass spectrometry/mass spectrometry. The efficacy of aPPD was
      determined upon oral administration to nu/nu nude mice bearing PC-3 human
      prostate cancer xenograft tumors. Immunohistochemical analysis of tumor tissues
      was performed to establish apoptotic indices and Ki-67 expression as markers of
      proliferation. The maximum solubility of aPPD in ethanol was 68.4 mg/ml. aPPD
      administered at a dose of 70 mg/kg yielded a T(max) of approximately 40 min and a
      C(max) value of 3.9 +/- 1.4 MUg/ml, and no toxicity was observed. aPPD
      accumulated largely in the stomach and small intestine and was also present in
      the brain. This dose engendered a significant delay in PC-3 tumor growth, an
      increase in apoptotic index, and a decrease in Ki-67 levels. We have shown that
      aPPD is a stable compound that can be formulated for oral gavage. Pharmacokinetic
      studies demonstrate the ability of this compound to be absorbed after oral
      administration. Future studies will assess the activity and pharmacokinetics of
      aPPD when administered in combination with standard chemotherapy.

PMID- 22481062
TI  - In-vitro cell tests using doxorubicin-loaded polymeric TiO2 nanotubes used for
      cancer photothermotherapy.
AB  - To determine the appropriate surfactant to be added to TiO(2) nanotubes (TNTs)
      for use in cancer photothermotherapy, this study measured the increase in
      temperature and examined the size distribution of TNT particles loaded with
      different surfactants during near-infrared irradiation. In addition, in-vitro
      cell (fluorescein isothiocyanate and MTT assay) tests were carried out to examine
      the cytotoxic effect of doxorubicin-loaded and polyvinyl alcohol-added TNTs
      (pTNTs). The mean particle size of the pTNTs was 151.8 nm with a particle size
      variation of less than 3 nm, which is low enough to flow through blood vessels
      without causing a blockage. The temperature of the pTNTs was ~47 degrees C, which
      is high enough to destroy cancer cells. Doxorubicin-loaded TNTs and pTNTs in
      combination with a near-infrared laser showed a cell viability of 4.5% - a
      sufficiently high cytotoxic effect.

PMID- 22481063
TI  - A phase II study of modified FOLFOX as first-line chemotherapy in advanced small
      bowel adenocarcinoma.
AB  - This study aimed at assessing the efficacy and safety of biweekly oxaliplatin in
      combination with continuous infusional 5-fluorouracil and leucovorin (modified
      FOLFOX regimen) in patients with advanced small bowel adenocarcinoma (SBA).
      Thirty-three eligible patients with previously untreated SBA received 85 mg/m(2)
      of oxaliplatin intravenously over a 2-h period on day 1, together with 400
      mg/m(2) of leucovorin over 2 h, followed by a 46-h infusion of 5-FU 2600 mg/m(2)
      every 2 weeks. All patients were evaluable for efficacy and toxicity. A median of
      nine cycles (range 3-18) was administered. The objective response rate was 48.5%
      [95% confidence interval (95% CI): 31-67%], with one complete response, 15
      partial responses, 12 stable diseases, and five progressions. The median time to
      progression was 7.8 months (95% CI: 6.0-9.6) and the median overall survival was
      15.2 months (95% CI: 11.0-19.4). Toxicity was fairly mild. Grade 3 toxicities
      included neutropenia (12.1%), thrombocytopenia (3.0%), nausea (6.1%), vomiting
      (3.0%), diarrhea (3.0%), peripheral neuropathy (9.1%), and fatigue (3.0%), and
      grade 4 toxicities occurred in none of the patients. The modified FOLFOX regimen
      is highly active and well tolerated as first-line chemotherapy for advanced SBA
      patients.

PMID- 22481064
TI  - Combination of docetaxel and cetuximab for penile cancer:  a case report and
      literature review.
AB  - Guidelines on the treatment of metastatic squamous cell carcinoma of the penis
      are limited to a few prospective trials. Cisplatin-based regimens represent the
      standard of treatment with promising activity of taxanes. Recently, epidermal
      growth factor receptor overexpression has been shown in these patients. We
      treated an elderly man with a docetaxel-cetuximab combination after failure of
      the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a
      reduction of (18)F-fluorodeoxyglucose uptake at PET/CT scan. Only mild mucositis
      and skin toxicity had been detected. Our case report, the first in the
      literature, shows that this combination is active and well tolerated in penile
      squamous cell carcinoma.

PMID- 22481065
TI  - Plasma insulin and glucose time courses after biliary pancreatic diversion in
      morbidly obese patients with and without diabetes.
AB  - BACKGROUND: The exact mechanism for the dramatic effect of surgical procedures
      for obesity on type 2 diabetes remains unknown. METHODS: Five diabetic morbidly
      obese patients and 5 nondiabetic morbidly obese patients undergoing
      biliopancreatic diversion were compared retrospectively. A 75-g trans-gastrostomy
      glucose tolerance test was administered on the fifth day postoperatively and a
      standard 75-g oral glucose tolerance test was performed on the seventh day
      postoperatively, with blood sampling for measuring plasma glucose and insulin
      levels at 0, 30, 60, 90, 120, and 180 minutes. RESULTS: All 5 diabetic patients
      were shown, at the same time, still to have diabetes or an impaired glucose
      tolerance test when tested through the biliopancreatic limb but patients were
      normal when tested through the new alimentary channel. No significant difference
      was seen in the nondiabetic patients. CONCLUSIONS: Biliopancreatic diversion can
      completely normalize the glycemic cycle in type 2 diabetes patients in the week
      after the intervention, even before any significant weight loss has occurred. The
      surgical procedure itself, designed to exclude most of the stomach, duodenum, and
      part of the jejunum, directly affects carbohydrate homeostasis.

PMID- 22481066
TI  - The predictive value of preoperative carcinoembryonic antigen level in the
      prognosis of colon cancer.
AB  - BACKGROUND: We evaluated factors associated with an increased preoperative
      carcinoembryonic antigen (CEA) level for colon cancer patients undergoing
      elective curative surgery and assessed whether this was associated with prognosis
      when accounting for other potential confounders. METHODS: Prospectively accrued
      data of patients with stage I, II, and III colon cancer undergoing surgery (1980
      2008) were retrieved retrospectively. Patients with a preoperative CEA level
      greater than 5 ng/mL (group B) were compared with those with a CEA level of 5
      ng/mL or less (group A). RESULTS: There were 651 patients (379 men) with a median
      age of 67 years (range, 21-94 y) and a median follow-up period of 5.9 years.
      Groups A (n = 451) and B (n = 200) had similar ages and tumor locations. Group B
      had larger tumors; more patients with T3 and N1/N2; and more patients with stage
      II/III tumors, and hence greater use of chemotherapy (P = .04). On multivariate
      analysis, patient age, tumor stage, and differentiation were associated with
      oncologic outcomes. A CEA level greater than 5 ng/mL was not associated
      independently with recurrence, recurrence-free survival (P = .47), or overall
      survival (P = .3). CONCLUSIONS: An increased preoperative CEA level is a marker
      for a more advanced tumor stage. For adequately staged patients, a high
      preoperative CEA level is not associated independently with oncologic outcomes.

PMID- 22481067
TI  - Pharmacological LXR activation reduces presence of SR-B1 in liver membranes
      contributing to LXR-mediated induction of HDL-cholesterol.
AB  - OBJECTIVE: Pharmacological LXR activation has anti-atherosclerotic actions in
      animal models. Part of these beneficial effects may be explained by accelerated
      reverse cholesterol transport since both plasma high density lipoprotein (HDL)
      cholesterol and fecal neutral sterol secretion are higher upon LXR activation.
      Mechanisms underlying these LXR-mediated effects have not been fully elucidated.
      METHODS: We investigated the roles of the isoforms LXRalpha and LXRbeta and the
      HDL cholesterol uptake receptor SR-B1 in modulation of cholesterol metabolism
      upon treatment of mice with the LXR ligand T0901317. RESULTS: HDL cholesterol was
      maximally 60% increased in a time-dependent fashion due to appearance of more and
      larger HDL particles. Fecal neutral sterol secretion was maximally induced after
      1 week treatment. T0901317 treatment induced fecal neutral sterol secretion by
      ~300% in wild-type but not in Lxralpha deficient mice. Surprisingly, LXR
      activation reduced SR-B1 protein amount in hepatic membranes, suggesting that
      this might contribute to elevated HDL cholesterol. However, T0901317 still
      elevated plasma HDL cholesterol in Sr-b1 deficient mice, suggesting that SR-B1 is
      not the only step involved in LXR-mediated induction of plasma HDL cholesterol.
      In addition, SR-B1 is not essential for LXR-induced cholesterol removal from the
      body. CONCLUSION: Induction of fecal neutral sterol secretion by T0901317
      critically depends on LXRalpha but not on LXRbeta. LXR activation reduces SR-B1
      in hepatic membranes, probably partly contributing to elevated HDL cholesterol.
      SR-B1 is not required to enhance fecal neutral sterol secretion.

PMID- 22481068
TI  - Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and a
      clinical diagnosis of familial combined hyperlipidemia.
AB  - OBJECTIVE: Rare mutations in the APOE gene, undetectable with the usual
      genotyping technique, are responsible for dominant familial
      dysbetalipoproteinemia (FD) and therefore could be easily misclassified as
      familial combined hyperlipidemia (FCHL). We aimed to identify APOE mutations
      associated with dominant combined hyperlipoproteinemia and to establish their
      frequency in subjects with a clinical diagnosis of FCHL. METHODS AND RESULTS: In
      279 unrelated subjects with FCHL in whom a functional LDLR mutation was excluded,
      sequencing of the entire APOE gene detected 9 carriers of a rare mutation: 5
      subjects (1.8%) with the R136S mutation (arginine at residue 136 changed to
      serine) and 4 subjects (1.4%) with the p.Leu149del mutation, a 3-bp inframe
      deletion that results in the loss of leucine at position 149. Both genetic
      defects were detected with similar frequency (2.5% and 1.3%, respectively) in an
      independent group of 160 FCHL subjects from other locations in Spain. Family
      studies demonstrated cosegregation of these APOE mutations with
      hyperlipoproteinemia. R136S carriers showed dysbetalipoproteinemia, while the
      lipid phenotype of p.Leu149del carriers was IIa or IIb. CONCLUSIONS: Rare APOE
      mutations are responsible for approximately 3.5% of FCHL cases in our population.
      APOE R136S and p.Leu149del induce autosomal dominant FD and a phenotype
      indistinguishable from FCHL, respectively.

PMID- 22481069
TI  - Thermal destruction of spin-polaron bands in the narrow-gap correlated
      semiconductors FeGa3 and FeSb2.
AB  - We report muon spin rotation spectra in the narrow-gap semiconductors FeGa(3) and
      FeSb(2) consistent with a narrow band of small spin polarons (SPs). The
      characteristic sizes obtained for these SPs are R(FeGa(3)) ~ 0.3-0.6 nm and
      R(FeSb (2)) ~ 0.3 nm, respectively. Such SP states are expected to originate from
      the exchange correlations between localized and itinerant electrons. Our data
      suggest that SP bands are formed at low temperature, but are destroyed by thermal
      fluctuations above 10 K in FeGa(3) and above 7 K in FeSb(2). Formation of such SP
      band states can explain many of the low-temperature properties of these
      materials.

PMID- 22481070
TI  - Dystrophic epidermolysis bullosa pruriginosa with autoantibodies against collagen
      VII.

PMID- 22481071
TI  - The improbable simplicity of the fusiform face area.
AB  - The fusiform face area (FFA) is described as an easily identifiable module on the
      fusiform gyrus. However, the organization of face-selective regions in ventral
      temporal cortex (VTC) is more complex than this prevailing view. We highlight
      methodological factors contributing to these complexities and the extensive
      variability in how the FFA is identified. We suggest a series of constraints to
      aid researchers when defining any functionally specialized region with a pleasing
      realization: anatomy matters.

PMID- 22481072
TI  - Early exposure to media violence and later child adjustment.
AB  - OBJECTIVE: The extent to which early childhood exposure to violent media is
      associated with subsequent adverse child functioning remains disconcerting. In
      this study, we examine whether preschool child exposure to what parents generally
      characterize as violent television programming predicts a range of second-grade
      mental health outcomes. METHODS: Participants are from the Quebec Longitudinal
      Study of Child Development (N = 1786). At 41 and 53 months, parents reported
      whether the child had viewed television shows and videos consisting of what they
      judged as violent content. RESULTS: According to parents, children watched on
      average 1.8 hours of mixed programming per day. Parent-reported child exposure to
      televised violence was associated with teacher-reported antisocial symptoms (beta
      = 0.180, 95% confidence interval [CI]: 0.026-0.333), emotional distress (beta =
      0.224, 95% CI: 0.010-0.438), inattention (beta = 0.349, 95% CI: 0.048-0.651), and
      lower global academic achievement (beta = -0.127, 95% CI: -0.237-0.017) in second
      grade. Violent televiewing was also associated with less child-reported academic
      self-concept (beta = -0.175, 95% CI: -0.296-0.053) and intrinsic motivation (beta
      = -0.162, 95% CI: -0.016-0.307) in second grade. Effects remained significant
      after adjusting for preexisting child and family characteristics such as baseline
      child aggression. CONCLUSIONS: This prospective study suggests risks associated
      with early childhood violent media exposure for long-term mental health in
      children. These findings, suggesting diffusive relationships between early
      childhood violent media exposure and negative socioemotional and academic
      outcomes, empirically support the notion that access to early childhood violent
      television represents a threat to population health and should be discouraged by
      adult caregivers.

PMID- 22481073
TI  - Prenatal drug exposure and peer victimization in early adolescence:  testing
      childhood anxiety/depression and aggression as possible mediators.
AB  - OBJECTIVE: Children who are prenatally exposed to drugs may be at risk for
      emotion dysregulation, including childhood anxiety/depression and aggression,
      potentially increasing their risk for peer victimization. The objectives of this
      study were to investigate how prenatal drug exposure relates to adolescent peer
      victimization and the mediating effects of childhood anxiety/depression and
      aggression. METHODS: Seventy-six prenatally drug exposed (PDE) and 38 nonexposed
      (NE) adolescent-caregiver dyads followed since birth and middle childhood,
      respectively, participated in an evaluation during adolescence. In middle
      childhood, caregivers reported on their child's anxiety/depression and
      aggression, and children reported on violence exposure. In adolescence,
      caregivers and adolescents responded to a parallel single-item measure of peer
      victimization. Analyses were conducted using multivariate linear and logistic
      regression models, adjusting for covariates, including violence exposure.
      RESULTS: One-third (33.3%, n = 35) of the sample endorsed peer victimization:
      40.8% PDE and 17.6% NE, p = .01. In middle childhood, PDE youth had more
      aggressive behaviors (11.92 vs 7.45, p < .01) and anxiety/depression symptoms
      (3.43 vs 1.76, p < .01) than NE youth. Anxious/depressed behavior during
      childhood mediated the association between prenatal drug exposure and adolescent
      peer victimization. Aggression was not a significant mediator. CONCLUSIONS: The
      consequences of prenatal drug exposure extend into adolescence. Prenatal drug
      exposure may interfere with emotion regulation, resulting in anxious/depressed
      behavior during childhood and significantly increasing the risk for peer
      victimization during adolescence, even in the presence of violence exposure.
      Strategies to reduce anxious/depressed behavior among children with a history of
      prenatal drug exposure may reduce adolescent peer victimization.

PMID- 22481074
TI  - Microsolvation and hydrogen bond interactions in Glycine Dipeptide: molecular
      dynamics and density functional theory studies.
AB  - Molecular dynamics (MD) simulations were carried out to study the conformational
      characteristics of Glycine Dipeptide (GD) in the presence of explicit water
      molecules for over 10 ns with a MD time step of 2 fs. The density functional
      theory (DFT) methods with 6-311G** basis set have been employed to study the
      effects of microsolvation on the conformations of GD with 5-10 water molecules.
      The interaction energy with BSSE corrections and the strength of the
      intermolecular hydrogen bond interactions have been analyzed. The Bader's Atoms
      in Molecules (AIM) theory has been employed to investigate H-bonding patterns in
      water interacting complexes. The natural bond orbital (NBO) analysis has been
      carried out to analyze the charge transfer between proton acceptor to the
      antibonding orbital of the XH bond in the hydrated complexes. NMR calculations
      have been carried out at B3LYP/6-311G (2d, 2p) level of theory to analyse the
      changes in structure and hydrogen bonding environment that occur upon solvation.

PMID- 22481075
TI  - In silico prediction of toxic action mechanisms of phenols for imbalanced data
      with Random Forest learner.
AB  - With an increasing need for the rapid and effective safety assessment of
      compounds in industrial and civil-use products, in silico toxicity exploration
      techniques provide an economic way for environmental hazard assessment. The
      previous in silico researches have developed many quantitative structure-activity
      relationships models to predict toxicity mechanisms for last decade. Most of
      these methods benefit from data analysis and machine learning techniques, which
      rely heavily on the characteristics of data sets. For Tetrahymena pyriformis
      toxicity data sets, there is a great technical challenge-data imbalance. The
      skewness of data class distribution would greatly deteriorate the prediction
      performance on rare classes. Most of the previous researches for phenol
      mechanisms of toxic action prediction did not consider this practical problem. In
      this work, we dealt with the problem by considering the difference between the
      two types of misclassifications. Random Forest learner was employed in cost
      sensitive learning framework to construct prediction models based on selected
      molecular descriptors. In computational experiments, both the global and local
      models obtained appreciable overall prediction accuracies. Particularly, the
      performance on rare classes was indeed promoted. Moreover, for practical usage of
      these models, the balance of the two misclassifications can be adjusted by using
      different cost matrices according to the application goals.

PMID- 22481076
TI  - Computational study on the inhibition mechanism of cruzain by nitrile-containing
      molecules.
AB  - Cysteine proteases from parasites as well as from mammals are promising drug
      targets for parasitic infections and systemic human diseases, respectively. Many
      reversible and irreversible inhibitors of this very large class of proteins have
      been designed. Among others, molecules with a nitrile moiety, which is a group
      that is susceptible to a nucleophilic attack by the enzyme, have been identified
      as good inhibitors. Although it is known that the nitrile group binds covalently
      to Cys25, there are no reports about the energetics involved in the mechanism of
      this process. Herein, density functional theory and quantum semi-empirical
      calculations were conducted in order to study the molecular recognition of
      cysteine proteases by nitrile-containing molecules. Results reported in this
      paper suggest an interaction that starts with a nucleophilic attack from the
      Cys25 to the inhibitor followed by a proton transfer from His162. Only one
      transition state was detected; however, we found the existence of an energy
      plateau in the potential energy surface. Based on the proposed mechanism, some
      structural features that could improve the biological activity of nitrile
      containing molecules toward cysteine proteases are discussed.

PMID- 22481077
TI  - Relationship between the structure and the enzymatic activity of crotoxin complex
      and its phospholipase A2 subunit: an in silico approach.
AB  - Crotoxin, one of the major toxins of South American rattlesnake Crotalus durissus
      subspecies, is an heterodimeric complex composed of two distinct subunits: a
      basic phospholipase A(2) (PLA(2), CB) and an acidic nontoxic catalytically
      inactive protein, crotapotin (CA). It's well known that CB has a high enzymatic
      activity; however the molecular aspects that determine this fact remain unknown.
      In this study, an in silico approach was used to predict the CA structure by
      homology modeling, and the crotoxin structure by means of molecular docking. CA
      structure was built using the software Modeller taking Crotalus atrox PLA(2)
      (1PP2:R) as a template. Different criteria measured by Procheck, Verify 3D and
      ProSA were indicative of the reliability and the proper fold for the predicted
      structural model of CA. Then, a combination of this model and CB crystal
      structure was used to build the structure of crotoxin complex through rigid-body
      protein-protein docking. The crotoxin-3D model suggested that by means of
      hydrophobic and pi-pi stacking interactions, CA-Y24 and CA-F119 interact with CB
      F24 and CB-F119, respectively. Those interactions could prevent the interfacial
      adsorption of the CB onto the lipid/water interface by blocking part of the
      interfacial binding surface of the PLA(2). This fact could explain the
      differences regarding to enzymatic activity between the crotoxin complex and CB.
      In addition, the crotoxin-3D model showed solvent-exposed regions of CA that
      could bind the receptor expressed in target cells.

PMID- 22481078
TI  - The adenosine deaminases of Plasmodium vivax and Plasmodium falciparum exhibit
      surprising differences in ligand specificity.
AB  - Plasmodium vivax and Plasmodium falciparum cause malaria, so proteins essential
      for their survival in vivo are potential anti-malarial drug targets. Adenosine
      deaminases (ADA) catalyze the irreversible conversion of adenosine into inosine,
      and play a critical role in the purine salvage pathways of Plasmodia and their
      mammalian hosts. Currently, the number of selective inhibitors of Plasmodium ADAs
      is limited. One potent and widely used inhibitor of the human ADA (hADA), erythro
      9-(2-hydroxy-3-nonly)adenine (EHNA), is a very weak inhibitor (K(i)=120 MUM) of
      P. falciparum ADA (pfADA). EHNA-like compounds are thus excluded from
      consideration as potential inhibitors of Plasmodium ADA in general. However, EHNA
      activity in P. vivax ADA (pvADA) has not been reported. Here we applied
      computational molecular modeling to identify ligand recognition mechanisms unique
      to P. vivax and P. falciparum ADA. Our biochemical experiments show that EHNA is
      at least 60-fold more potent against pvADA (K(i)=1.9 MUM) than against pfADA. The
      D172A pvADA mutant is bound even more tightly (K(i)=0.9 MUM). These results
      improve our understanding of the mechanisms of ADA ligand recognition and species
      selectivity, and facilitate the rational design of novel EHNA-based ADA
      inhibitors as anti-malarial drugs. To demonstrate a practical application of our
      findings we have computationally predicted a novel potential inhibitor of pvADA
      that will not interact with the human ADA.

PMID- 22481079
TI  - TDDFT studies on the structures and ECD spectra of chiral bisarylimidos bearing
      different lengths of o-alkoxy chain-substituted polyoxomolybdates.
AB  - The chiroptical properties of bisarylimidos bearing o-alkoxy chain-substituted
      polyoxomolybdates [Mo(6)O(17)(2,2'-NC(6)H(4)OC(n)H(2n)OC(6)H(4)N)](2-) [n=4(2),
      6(3+/-), 8(4)] were investigated using the time-dependent density functional
      method. The results showed that the studied chiral polyoxometalates (POMs)
      manifested similar absorption sites but displayed different shapes and magnitudes
      in their electronic circular dichroism (ECD) spectra. The ECD spectra of the
      studied chiral POMs originated from charge-transfer (CT) transitions from
      arylimido fragments to the POM cages and from oxygen atoms to the molybdenum
      atoms in the POM cages. The o-alkoxy chain served as a scaffold for generating
      chirality rather than contributing to the ECD spectrum of the studied POMs. The
      induced chiralities of the POM cages were defined by the CT transitions, which
      were completely localized on the POM cages. Furthermore, the long-range corrected
      CAM-B3LYP hybrid functional and a basis set that is larger than Lanl2DZ should be
      used for ECD calculations of chiral POMs. Our work establishes the use of
      computational studies to investigate the chiroptical properties of chiral POMs
      and provides theoretical interpretations.

PMID- 22481080
TI  - Object recognition testing: statistical considerations.
AB  - The object recognition task is a commonly used test for the assessment of memory
      functions in rodents. In this paper different aspects concerning the analysis of
      object recognition data are discussed. Using a set of experimental studies and
      fictive data sets, it was shown that the absolute discrimination measure (d1)
      behaves different from the ratio measures (d2 and d3). Furthermore, it is
      suggested that, besides group differences, one should also examine whether each
      individual group actually discriminates between the novel and the familiar
      object. For this purpose, the use of a fictive group showing no discrimination is
      advisable. Furthermore, on basis of 48 object recognition task studies it is
      shown that discrimination performance does not fall significantly below zero.
      Therefore one-sided testing is allowed, provided that place- or object biases can
      be ruled out. Finally, it was shown that differences in exploration levels may
      affect the statistical evaluation of group differences. Several suggestions for
      statistical analysis are given.

PMID- 22481081
TI  - Observe, simplify, titrate, model, and synthesize: a paradigm for analyzing
      behavior.
AB  - Phenomena in behavior and their underlying neural mechanisms are exquisitely
      complex problems. Infrequently do we reflect on our basic strategies of
      investigation and analysis, or formally confront the actual challenges of
      achieving an understanding of the phenomena that inspire research. Philip
      Teitelbaum is distinct in his elegant approaches to understanding behavioral
      phenomena and their associated neural processes. He also articulated his views on
      effective approaches to scientific analyses of brain and behavior, his vision of
      how behavior and the nervous system are patterned, and what constitutes basic
      understanding. His rubrics involve careful observation and description of
      behavior, simplification of the complexity, analysis of elements, and re
      integration through different forms of synthesis. Research on the development of
      huddling behavior by individual and groups of rats is reviewed in a context of
      Teitelbaum's rubrics of research, with the goal of appreciating his broad and
      positive influence on the scientific community.

PMID- 22481082
TI  - Object recognition testing: rodent species, strains, housing conditions, and
      estrous cycle.
AB  - The object recognition task (ORT) allows assessing learning and memory processes
      in rodents. In this study, two areas in which knowledge about the ORT could be
      extended were addressed; i.e. generality to species and strains, and intervening
      variables including housing and estrous cycle. Regarding generality to species
      and strains, the ORT performance of golden hamsters was assessed. The hamsters
      showed sufficient exploration times, object recognition performance, and a
      retention-interval dependent decline similar to rats and mice. Subsequently, we
      tested three mouse strains which have not been described before in the ORT; i.e.
      OF1, NMRI, and SJL mice. OF1 and NMRI strains performed equally well, whereas the
      SJL strain showed low exploration times and no memory retention. Therefore, the
      SJL strain is unsuited for ORT experiments using a 1h retention interval and a
      fixed (3 min) trial duration. Furthermore, the sensitivity to a pharmacological
      memory deficit model (scopolamine) was tested in three rat strains. Each strain
      showed a dose dependent relationship, but the least effective dose of scopolamine
      differed among the three strains, the effect being greater in the order of
      Wistar, Long-Evans, Hooded Lister rats. Finally, to investigate potential
      intervening variables in the ORT, the effects of housing conditions and estrous
      cycle were investigated with rats. Single housing resulted in absolute higher
      performance than social housing. Furthermore, females in pro-estrus/estrus showed
      better performance compared to females in met-estrus/di-estrus. Taken together,
      object recognition appears to be a common ability of rodent species, but
      different strains have different memory capacities and sensitivities to
      scopolamine, individual housing leads to higher performance, and performance of
      females is dependent on the estrous cycle phase. Thus, rodent species, strain,
      housing, and estrous cycle should be taken into consideration in ORT studies.

PMID- 22481083
TI  - Apoptosome-dependent caspase activation proteins as prognostic markers in Stage
      II and III colorectal cancer.
AB  - BACKGROUND: Critical to successful execution of mitochondrial-mediated apoptosis
      is apoptosome formation and subsequent activation of caspases. Defects in this
      pathway have an important role in colorectal carcinogenesis and chemoresistance;
      therefore, the expression of apoptosome-associated proteins may be associated
      with clinical outcome and response to chemotherapy. METHODS: Here we performed a
      systematic analysis of the immunohistochemical expression of the key proteins
      involved in apoptosome-dependent caspase activation (APAF1, Pro-caspases 9 and 3,
      SMAC, and XIAP) in a cohort of Stage II and III colorectal cancer patients from a
      Phase III trial of adjuvant 5-fluorouracil-based chemotherapy vs postoperative
      observation alone. RESULTS: Survival analysis indicated that of the apoptosome
      associated proteins examined here, Pro-caspase 3 and APAF1 have potential
      clinical utility as predictive markers in Stage II and III colorectal cancer,
      respectively. Interestingly, we identified APAF1 staining to be associated with
      better recurrence-free and overall survival in patients receiving chemotherapy.
      CONCLUSION: These studies reveal the importance of the apoptosome-dependent
      caspase activation pathway, specifically Pro-caspase 3 and APAF1 proteins, for
      predicting both prognosis and response to therapy.

PMID- 22481084
TI  - Induced osteoclastogenesis by fluoroquinolones in unstimulated and stimulated
      human osteoclast precursor cells.
AB  - Fluoroquinolones (FQs) are a class of antibiotics with a broad spectrum of
      activity, known to disturb bone metabolism. The aim of this work was to
      characterize the cellular and molecular effects of five FQs (ofloxacin,
      norfloxacin, ciprofloxacin, levofloxacin and moxifloxacin) in unstimulated and
      stimulated human osteoclast precursors. Peripheral blood mononuclear cells (PBMC)
      were cultured in the absence (unstimulated) or in the presence of
      osteoclastogenic factors (M-CSF and RANKL, stimulated), and were treated with FQs
      (0.3*10(-9)-10(-3) M), for 21 days. In unstimulated PBMC cultures, FQs (excepting
      moxifloxacin) exhibited a high osteoclastogenic potential, as shown by a
      significant increase in the expression of osteoclastic genes, TRAP activity and,
      specially, number of TRAP-positive multinucleated cells and calcium phosphate
      resorbing ability, suggesting the presence of mature and functional osteoclasts.
      Norfloxacin and levofloxacin induced the higher effect, followed by ciprofloxacin
      and ofloxacin. A decrease on apoptosis and an increase on M-CSF expression might
      have a possible contribution in the observed cellular behavior. In stimulated
      PBMC cultures, FQs further increase the osteoclastogenic response induced by M
      CSF and RANKL (except ofloxacin). However, the osteoclastogenic response was much
      lower than that observed in unstimulated PBMC cultures. Both in unstimulated and
      stimulated PBMC cultures, for most of the FQs, the osteoclastogenic effects were
      observed in a wide range of concentrations, representative of plasmatic and
      tissue levels attained in several clinical settings. The various FQs differed on
      the stimulatory concentration range, the extent of the induced osteoclastogenic
      response and, also, on the dose- and time-dependent profile. Nevertheless, at
      high concentrations all the FQs seemed to elicit an increase on apoptosis.
      Additionally, some differences were noted in the intracellular signaling pathways
      tested, namely NFkB, MEK and PGE2 production. Results suggest that, considering
      the inter-individual variability of the FQs pharmacokinetics, the detailed
      biological profile of each FQ on bone cells is of utmost importance to clarify
      the effects of these compounds on bone metabolism.

PMID- 22481085
TI  - Three to six ambiguities in immittance spectroscopy data fitting.
AB  - Several important ambiguities in immittance spectroscopy (IS) model data-fitting
      results are identified and illustrated by means of complex-nonlinear-least
      squares (CNLS) fits of experimental and synthetic frequency response data. A well
      known intrinsic ambiguity, following from Maxwell's electromagnetic equations,
      arises from the indistinguishability in external measurements of conduction and
      displacement currents. Usual fit models for either dielectric or conductive
      system situations, such as the Davidson-Cole one, only involve a strength
      parameter, a dielectric constant, a characteristic relaxation time, and a
      fractional exponent and lead to no additional ambiguities. But the situation is
      different for more powerful and useful general models, such as ordinary or
      anomalous diffusion Poisson-Nernst-Planck ones: PNP and PNPA, used here, whose
      historical background, current status, and applicability are described and
      discussed herein. They apply to two different kinds of experimental IS situations
      and involve several additional, potentially free fit parameters, such as the
      mobilities of positive and negative charge carriers, and generation-recombination
      parameters that determine the partial or complete dissociation of a neutral
      entity of concentration N(0) into positive and negative charge carriers of equal
      concentration, c(0). Then, several additional ambiguities appear that may require
      information about the material system involved for their adequate resolution.

PMID- 22481086
TI  - Autoimmune hepatitis in the postpartum period.
AB  - AIM: Autoimmune hepatitis (AIH) presenting primarily in the postpartum period has
      rarely been reported. METHODS: The medical data of 58 female patients diagnosed
      with AIH was assessed. RESULTS: In the study population, three (5.1%) patients
      were diagnosed postpartum. Based on clinical, laboratory and liver biopsy
      findings, two of these patients were considered to have subclinical AIH and were
      diagnosed by disease flare after delivery. The remaining patient was considered
      as new onset of AIH in the postpartum period. CONCLUSIONS: AIH can present in the
      postpartum and should be actively considered among the differential diagnosis if
      liver dysfunction is observed after delivery.

PMID- 22481087
TI  - End-stage liver disease: prevalence, risk factors and clinical characteristics in
      a cohort of HIV-HCV coinfected Han Chinese.
AB  - INTRODUCTION: Since the advent of combined antiretroviral therapy (cART), liver
      related mortality has become the leading cause of non-AIDS-related deaths in
      human immunodeficiency virus (HIV) infected patients in Western countries.
      OBJECTIVE: To investigate the incidence, mortality and risk factors of end-stage
      liver disease (ESLD) in HIV and hepatitis C virus (HCV) coinfected former plasma
      donors (FPDs) and blood recipients (BRs). METHOD: A retrospective study was
      conducted. RESULTS: Of 321 HIV-HCV coinfected patients, 42 (13.1%) developed ESLD
      and 40 (12.5%) died. Factors that were independently associated with ESLD
      included older age at baseline (Odds ratios [OR]: 2.444, P=0.035), alanine
      aminotransferase (ALT) greater or equal to 2 (the upper limit of normal [ULN]) at
      the end of follow-up (OR: 16.460, P=0.000), hepatitis B virus (HBV) (OR: 2.525,
      P=0.043), CDC stage C (OR: 5.806, P=0.001), duration of cART greater than 5 years
      (OR: 3.256, P=0.010), and CD4 count greater or equal to 200 cells/mm(3) at the
      end of follow-up (OR: 0.383, P=0.016). The probability of developing ESLD in HIV
      HCV coinfected BRs was significantly higher than in FPDs (P=0.008). Mortality was
      also significantly higher in HIV-HCV coinfected patients with ESLD than in those
      without ESLD (P=0.000). CONCLUSION: In the cART era, ESLD was common among HIV
      HCV coinfected Han Chinese patients and was responsible for reducing patient
      survival time.

PMID- 22481088
TI  - Primary liver cancer among cirrhosis patients with and without HIV infection.

PMID- 22481089
TI  - Autoantibodies in autoimmune hepatitis: antinuclear antibodies (ANA).

PMID- 22481090
TI  - Commentary on 'Development of off-the-shelf stent grafts for juxtarenal abdominal
      aortic aneurysms'.

PMID- 22481091
TI  - Redox signaling loops in the unfolded protein response.
AB  - The endoplasmic reticulum (ER) is the first compartment of secretory pathway. It
      plays a major role in ER chaperone-assisted folding and quality control,
      including post-translational modification such as disulfide bond formation of
      newly synthesized secretory proteins. Protein folding and assembly takes place in
      the ER, where redox conditions are distinctively different from the other
      organelles and are favorable for disulfide formation. These reactions generate
      the production of reactive oxygen species (ROS) as a byproduct of thiol/disulfide
      exchange reaction among ER oxidoreductin 1 (Ero1), protein disulfide isomerase
      (PDI) and ER client proteins, during the formation of disulfide bonds in nascent
      or incorrectly folded proteins. When uncontrolled, this phenomenon perturbs ER
      homeostasis, thus aggravating the accumulation of improperly folded or unfolded
      proteins in this compartment (ER stress). This results in the activation of an
      adaptive mechanism named the unfolded protein response (UPR). In mammalian cells,
      the UPR is mediated by three ER-resident membrane proteins (PERK, IRE1 and ATF6)
      and regulates the expression of the UPR target genes, which themselves encode ER
      chaperones, folding enzymes, pro-apoptotic proteins and antioxidants, with the
      objective of restoring ER homeostatic balance. In this review, we will describe
      redox dependent activation (ER) and amplification (cytosol) loops that control
      the UPR and the consequences these regulatory loops have on cell fate and
      physiology.

PMID- 22481092
TI  - Paxillin phosphorylation and complexing with Erk and FAK are regulated by PLD
      activity in MDA-MB-231 cells.
AB  - MDA-MB-231 cells are highly aggressive human breast adenocarcinoma cells that
      depend on PLD activity for survival. In response to the stress of serum
      withdrawal, there is increased motility and invasiveness of these cells that is
      associated with a rapid increase in PLD activity. In addition, PLD activity is
      elevated in response to most mitogenic signals. Similar to PLD, paxillin, a focal
      adhesion adaptor protein, and Erk, mitogen-activated protein kinase, play vital
      roles in cell motility through regulation of focal adhesion dynamics. Here, we
      addressed whether there is a functional correlation between paxillin and PLD that
      may influence cancer cell motility. We investigated the role of PLD activity on
      paxillin regulation, Erk activation and formation of a paxillin-Erk and paxillin
      FAK association. Inhibition of PLD activity led to an increase in paxillin
      tyrosine phosphorylation, a decrease in Erk activation, as measured by
      phosphorylation, and enhanced association of paxillin with Erk. In addition, we
      found that paxillin tyrosine phosphorylation depends upon Erk activity and may be
      a consequence of an increased association with FAK. Taken together, these results
      suggest that Erk activity is governed by PLD activity and regulates the tyrosine
      phosphorylation of paxillin, potentially explaining its role in cell motility.
      This study indicated that PLD, Erk, paxillin and FAK participate in the same
      signaling pathway in this breast cancer cell line.

PMID- 22481093
TI  - New advances on the functional cross-talk between insulin-like growth factor-I
      and estrogen signaling in cancer.
AB  - There is increasing awareness that estrogens may affect cell functions through
      the integration with a network of signaling pathways. The IGF system is a
      phylogenetically highly conserved axis that includes the insulin receptor (IR)
      and the insulin-like growth factor I receptor (IGF-IR) pathways, which are of
      crucial importance in the regulation of metabolism and cell growth in
      relationship to nutrient availability. Numerous studies nowadays document that
      estrogens cooperate with IGF system at multiple levels both in physiology and in
      disease. Several studies have focused on this bidirectional cross-talk in central
      nervous system, in mammary gland development and in cancer. Notably, cancer cells
      show frequent deregulation of the IGF system with overexpression of IR and/or IGF
      IR and their ligands as well as frequent upregulation of the classical estrogen
      receptor (ER)alpha and the novel ER named GPER. Recent studies have, therefore,
      unraveled further mechanisms of cross-talk involving membrane initiated estrogen
      actions and the IGF system in cancer, that converge in the stimulation of pro
      tumoral effects. These studies offer hope for new strategies aimed at the
      treatment of estrogen related cancers in order to prevent an estrogen-independent
      and more aggressive tumor progression.

PMID- 22481094
TI  - New insights in the activity of voltage sensitive phosphatases.
AB  - The Ciona intestinalis voltage sensitive phosphatase (Ci-VSP) was the first
      proven enzyme to be under direct control of the membrane potential. Ci-VSP
      belongs to a family of proteins known as Protein Tyrosine Phosphatases (PTP),
      which are a group of enzymes that catalyze the removal of phosphate groups from
      phosphatidylinositides and phosphorylated tyrosine residues on proteins. What
      makes Ci-VSP and similar phosphatases unique is the presence of a Voltage Sensing
      Domain (VSD) in their N-terminus. The VSD of Ci-VSP shares high homology with
      those from voltage-gated channels and confers voltage sensitivity to these
      enzymes. The catalytic domain of Ci-VSP displays extraordinary structural and
      functional similarities to PTEN. This latter protein is encoded by the
      Phosphatase and Tensin homolog deleted from chromosome 10 gene, thus its name,
      and it is known as a tumor suppressor. The resemblance between these proteins has
      prompted the use of PTEN as a template for the study of Ci-VSP and produced a
      rapid advance in our understanding of the mechanism of activity of Ci-VSP. This
      review will be focused on discussing recent advances in the understanding of the
      activation mechanism for these molecules known as electrochemical coupling.

PMID- 22481095
TI  - Tetrakis(thiadiazole)porphyrazines. 8. Singlet oxygen production, fluorescence
      response and liposomal incorporation of tetrakis(thiadiazole)porphyrazine
      macrocycles [TTDPzM] (M = Mg(II)(H2O), Zn(II), Al(III)Cl, Ga(III)Cl, Cd(II),
      Cu(II), 2H(I)).
AB  - The photoactivity for the generation of singlet oxygen, (1)O(2), the key
      cytotoxic agent in the anticancer treatment known as photodynamic therapy (PDT),
      and the fluorescence response of the highly electron-deficient
      tetrakis(thiadiazole)porphyrazines of formula [TTDPzM] (M = Mg(II)(H(2)O),
      Zn(II), Al(III)Cl, Ga(III)Cl, Cd(II), Cu(II), 2H(I)) were examined (c ? 10(-5) M)
      in dimethylformamide (DMF) and/or in DMF preacidified with HCl (DMF/HCl; [HCl] =
      1-4 * 10(-4) M). The singlet oxygen quantum yield (Phi(Delta)) of all the
      compounds was determined by using a widely employed procedure based on the
      selective oxidation of the 1,3-diphenylisobenzofuran (DPBF), modified in part as
      reported. The list of the Phi(Delta) values indicates excellent photosensitizing
      properties for the series of compounds carrying "closed shell" metal ions, with
      values measured in DMF/HCl respectful of the "heavy atom effect" for the first
      four lighter centers, increasing in the order Mg(II) < Al(III) < Zn(II) <
      Ga(III). Data of Phi(Delta) concerning the unmetalated species [TTDPzH(2)],
      present in solution in the form of the corresponding anion [TTDPz](2-), and the
      Cd(II) and Cu(II) complexes are also presented and discussed. Extensive
      discussion is also developed on the fluorescence quantum yield values Phi(F),
      with data on the Mg(II) and Al(III) compounds in DMF/HCl (0.44 and 0.53,
      respectively) indicative of promising perspectives for applications in
      fluorescence imaging techniques. The Phi(F) data of the studied porphyrazine
      series, Phi(F)(Pz), correlate linearly with those of the homologous
      phthalocyaninato complexes, Phi(F)(Pc), suggesting a closely similar behaviour
      between the two classes of compounds. The incorporation of [TTDPzZn] into
      liposomes was successfully achieved following the detergent depletion method
      (DDM) from a mixed micellar solution by means of gel-filtration. Retention of
      [TTDPzZn] (~40%) in its photoactive monomeric form into liposomes is proved by
      absorption and fluorescence spectra, this proposing the Zn(II) complex as a
      promising candidate for use in PDT.

PMID- 22481096
TI  - Four decades of health economics through a bibliometric lens.
AB  - In this paper, we take a bibliometric tour of the last forty years of health
      economics using bibliographic "metadata" from EconLit supplemented by citation
      data from Google Scholar and our own topical classifications. We report the
      growth of health economics (we find 33,000 publications since 1969-12,000 more
      than in the economics of education) and list the 300 most-cited publications
      broken down by topic. We report the changing topical and geographic focus of
      health economics (the topics 'Determinants of health and ill-health' and 'Health
      statistics and econometrics' both show an upward trend, and the field has
      expanded appreciably into the developing world). We also compare authors,
      countries, institutions and journals in terms of the volume of publications and
      their influence as measured through various citation-based indices (Grossman, the
      US, Harvard and the JHE emerge close to or at the top on a variety of measures).

PMID- 22481097
TI  - Mechanical constraint and release generates long, ordered horizontal pores in
      anodic alumina templates.
AB  - We describe the formation of long, highly ordered arrays of planar oriented
      anodic aluminum oxide (AAO) pores during plane parallel anodization of thin
      aluminum 'finger' microstructures fabricated on thermally oxidized silicon
      substrates and capped with a silicon oxide layer. The pore morphology was found
      to be strongly influenced by mechanical constraint imposed by the oxide layers
      surrounding the Al fingers. Tractions induced by the SiO(2) substrate and capping
      layer led to frustrated volume expansion and restricted oxide flow along the
      interface, with extrusion of oxide into the primary pore volume, leading to the
      formation of dendritic pore structures and meandering pore growth. However,
      partial relief of the constraint by a delaminating interfacial fracture, with its
      tip closely following the anodization front, led to pore growth that was highly
      ordered with regular, hexagonally packed arrays of straight horizontal pores up
      to 3 um long. Detailed characterization of both straight and dendritic planar
      pores over a range of formation conditions using advanced microscopy techniques
      is reported, including volume reconstruction, enabling high quality 3D
      visualization of pore formation.

PMID- 22481098
TI  - Safety and efficacy of epoprostenol therapy in pulmonary veno-occlusive disease
      and pulmonary capillary hemangiomatosis.
AB  - BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary
      hemangiomatosis (PCH) are rare causes of pulmonary hypertension. There is no
      proven medical therapy to treat these diseases, and lung transplantation is
      thought to be the only cure. Administration of vasodilators including
      epoprostenol sometimes causes massive pulmonary edema and could be fatal in these
      patients. METHODS AND RESULTS: Eight patients were treated with epoprostenol for
      387.3+/-116.3 days (range, 102-1,063 days), who were finally diagnosed with PVOD
      or PCH by pathological examination. The maximum dose of epoprostenol given was
      55.3+/-10.7 ng.kg(-1).min(-1) (range, 21.0-110.5 ng.kg(-1).min(-1)). With careful
      management, epoprostenol therapy significantly improved the 6-min walk distance
      (97.5+/-39.2 to 329.4+/-34.6 m, P<0.001) and plasma brain natriuretic peptide
      levels (381.3+/-136.8 to 55.2+/-14.4 pg/ml, P<0.05). The cardiac index
      significantly increased from 2.1+/-0.1 to 2.9+/-0.3 L.min(-1).m(-2) (P<0.05).
      However, pulmonary artery pressure and pulmonary vascular resistance were not
      significantly reduced. For 4 patients, epoprostenol therapy acted as a bridge to
      lung transplantation. For the other patients who had no chance to undergo lung
      transplantation, epoprostenol therapy was applied for 528.0+/-216.6 days and the
      maximum dose was 63.9+/-19.0 ng.kg(-1).min(-1). CONCLUSIONS: This study data
      suggest that cautious application of epoprostenol can be considered as a
      therapeutic option in patients with PVOD and PCH.

PMID- 22481099
TI  - Impact of early intravenous epinephrine administration on outcomes following out
      of-hospital cardiac arrest.
AB  - BACKGROUND: The effectiveness of epinephrine administration for cardiac arrests
      has been shown in animal models, but the clinical effect is still controversial.
      METHODS AND RESULTS: A prospective, population-based, observational study in
      Osaka involved consecutive out-of-hospital cardiac arrest (OHCA) patients from
      January 2007 through December 2009. We evaluated the outcomes among adult non
      traumatic bystander-witnessed OHCA patients for whom the local protocol directed
      the emergency medical service personnel to administer epinephrine. After
      stratifying by first documented cardiac rhythm, outcomes were compared among the
      following groups: non-administration, <=10, 11-20 and >=21 min as the time from
      emergency call to epinephrine administration. A total of 3,161 patients were
      eligible for our analyses, among whom 1,013 (32.0%) actually received
      epinephrine. The epinephrine group had a significantly lower rate of
      neurologically intact 1-month survival than the non-epinephrine group (4.1% vs.
      6.1%, P=0.028). In cases of ventricular fibrillation (VF) arrest, patients in the
      early epinephrine group who received epinephrine administration within 10 min had
      a significantly higher rate of neurologically intact 1-month survival compared
      with the non-epinephrine group (66.7% vs. 24.9%), though other epinephrine groups
      did not. In cases of non-VF arrest, the rate of neurologically intact 1-month
      survival was low, irrespective of epinephrine administration. CONCLUSIONS: The
      effectiveness of epinephrine after OHCA depends on the time of administration.
      When epinephrine is administered in the early phase, there is an improvement in
      neurological outcome from OHCA with VF.

PMID- 22481100
TI  - Low-dose beta-blocker in combination with milrinone safely improves cardiac
      function and eliminates pulsus alternans in patients with acute decompensated
      heart failure.
AB  - BACKGROUND: The purpose of this study was to determine whether a low-dose beta
      blocker, in combination with milrinone, improves cardiac function in acute
      decompensated heart failure (ADHF) with tachycardia. METHODS AND RESULTS: Twenty
      ADHF patients (New York Heart Association classification III, n=1, and IV, n=19;
      heart rate [HR], 107+/-12 beats/min; left ventricular ejection fraction, 24+/-7%;
      cardiac index [CI], 2.2+/-0.6 L.min(-1).m(-2); pulmonary capillary wedge pressure
      [PCWP], 26+/-8 mmHg) were enrolled in this study. The patients first underwent
      conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5
      6.0 ug.kg(-1).min(-1); i.v.), which is an ultra-short-acting beta(1)-selective
      blocker, was then added to the treatment regimen to study its effect on
      hemodynamics. Low-dose landiolol (1.5 ug.kg(-1).min(-1)) significantly reduced HR
      by 11% without changing blood pressure (BP) and CI, whereas higher doses (>=3.0
      ug.kg(-1).min(-1)) tended to decrease BP and CI while increasing PCWP and
      systemic vascular resistance. After treatment with landiolol (1.5 ug.kg(-1).min(
      1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate
      pressure product, filling time/RR, E/e', and Tei index were significantly
      improved. CONCLUSIONS: A low-dose beta-blocker in combination with milrinone
      improved cardiac function in ADHF patients with tachycardia; therefore, it may be
      considered as an adjunct therapy for use when standard therapy with milrinone is
      not effective at slowing HR.

PMID- 22481101
TI  - The cholesterol paradox in atrial fibrillation.

PMID- 22481103
TI  - Waon therapy upregulates Hsp90 and leads to angiogenesis through the Akt
      endothelial nitric oxide synthase pathway in mouse hindlimb ischemia.
AB  - BACKGROUND: Thermal therapy, namely Waon therapy, has previously been reported to
      regulate nitric oxide (NO) and endothelial NO synthase (eNOS) and augment
      ischemia-induced angiogenesis in mice and improve limb ischemia in patients with
      peripheral artery disease. The aim of this study was to clarify the precise
      mechanism by which Waon therapy augments angiogenesis in mice with hindlimb
      ischemia. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in
      apolipoprotein E-deficient mice and Waon therapy was performed for 5 weeks. Heat
      shock protein 90 (Hsp90), phosphorylated-Akt, and phosphorylated-eNOS were
      detected in arterial endothelial cells of ischemic hindlimbs and all were
      upregulated by Waon therapy compared to controls. Waon therapy also increased
      serum concentrations of nitrite and nitrate. Capillary density and the ischemic
      limb/normal side blood perfusion ratio monitored by laser Doppler perfusion
      imaging in the Waon therapy group were significantly increased beyond those in
      the control group. The effect of Waon therapy on angiogenesis through the
      activation of the Hsp90/Akt/eNOS pathway was attenuated by the administration of
      a Hsp90 inhibitor. CONCLUSIONS: It is suggested that Waon therapy upregulates
      Hsp90, which contributes to the activation of the Akt/eNOS/NO pathway, and
      induces angiogenesis in mice with hindlimb ischemia.

PMID- 22481104
TI  - Anxiety disorder is associated with nocturnal and early morning hypertension with
      or without morning surge: ambulatory blood pressure monitoring.
AB  - BACKGROUND: Nocturnal and early morning hypertension are both significant risk
      factors for cardiovascular events. It remains unclear whether anxiety disorder
      affects nocturnal blood pressure (BP), early morning BP, or BP pattern in
      hypertensive patients. METHODS AND RESULTS: One hundred and twenty consecutive
      hypertensive outpatients (77 men and 43 women; mean age, 66+/-11 years) were
      divided into 2 groups based on Hospital Anxiety and Depression Scale (HADS)
      score: a control group (n=78; HADS <=10) and an anxiety group (42 patients; HADS
      >=11). Nocturnal BP, early morning BP, morning BP surge (defined as BP rise >=50
      mmHg), and BP pattern (extreme-dipper/dipper/non-dipper/riser) were measured on
      ambulatory BP monitoring. Clinical characteristics and BP were also evaluated at
      physician check-up. There was no significant difference between the 2 groups for
      BP check-up, but nocturnal and early morning BP were significantly higher in the
      anxiety group (142+/-16 mmHg and 152+/-21 mmHg) than in the control group (126+/
      14 mmHg and 141+/-18 mmHg). With regard to patients with morning BP surge,
      nocturnal and early morning BP were also significantly higher in the anxiety
      group. The relative risk of existing anxiety disorders in riser-type hypertension
      was 4.48-fold higher (95% confidence interval: 1.58-12.74; P<0.005) than in
      dipper-type hypertension. CONCLUSIONS: Anxiety disorder is associated with
      nocturnal and early morning hypertension, and may be a risk factor for
      cardiovascular events.

PMID- 22481105
TI  - Mode of death in patients with heart failure and reduced vs. preserved ejection
      fraction: report from the registry of hospitalized heart failure patients.
AB  - BACKGROUND: The mode of death has not been investigated in the registry data of
      patients with heart failure and reduced ejection fraction (HFREF) vs. preserved
      ejection fraction (HFPEF). The aim of the present study was therefore to carry
      out this comparison. METHODS AND RESULTS: The Japanese Cardiac Registry of Heart
      Failure in Cardiology (JCARE-CARD) prospectively studied the characteristics and
      treatments in a broad sample of 2,675 patients hospitalized with worsening HF,
      and followed them for an average of 2.1 years. This study included 323 patients
      in whom information on both the mode of death and left ventricular EF on
      echocardiography could be obtained. The mode of death was cardiovascular (CV) in
      63% (including 17% sudden, 36% HF, 3% myocardial infarction, and 3% stroke), non
      CV in 23%, and unknown in 14%. The prevalence of CV death including sudden death
      was high in patients with HFREF compared to HFPEF (68% vs. 58%, P=0.020). HF
      death, the most common mode of death, was similar between groups (37% vs. 35%,
      P=0.694). In contrast, non-CV mortality was significantly higher in HFPEF than
      those with HFREF (28% vs. 18%, P=0.021). CONCLUSIONS: In 60-70% of deaths the
      mode was CV, and HF death was the most common mode of death in either HFREF or
      HFPEF. The prevalence of sudden death was lower, and that of non-CV death higher,
      in HFPEF compared with HFREF.

PMID- 22481106
TI  - What is optimal revascularization for hemodialysis patients?

PMID- 22481107
TI  - Investigation of unsaponifiable matter of plant oils and isolation of eight
      phytosterols by means of high-speed counter-current chromatography.
AB  - Phytosterols are minor components of plant oils. Due to their beneficial effect
      on human serum cholesterol level, new products supplemented with phytosterols
      have been marketed. Commercial phytosterol standards are frequently of
      insufficient purity, very expensive, only available in (semi-) synthetic form or
      not available at all. For this reason we aimed to explore the unsaponifiable
      matter of three plant oils (rapeseed oil, linseed oil and olive oil) in order to
      study their compositions and to purify several phytosterols. We fractionated ~
      100 mg of the unsaponifiable matter of the plant oils with high-speed counter
      current chromatography (HSCCC) by the combination of an enrichment step and a
      purification step. In the first part (enrichment step) composition of
      phytosterols, alkanes, fatty alcohols from 14:0 to 30:0 including isomers, 15
      nonacosanone and other ketones as well as further minor compounds in the
      different fractions was studied by GC/MS. By means of the solvent system n
      hexane/methanol/aqueous silver nitrate solution (34/24/1, v/v/v) in normal phase
      mode (tail-to-head) beta-sitosterol could be isolated (6.4 mg, purity >= 99%) and
      several phytosterols (e.g. citrostadienol, cycloeucalenol and erythrodiol) could
      be enriched. Moreover, the fast eluting hydrocarbons squalene and nonacosane as
      well as the later eluting phytol (pure, 7 mg) and geranyl geraniol could also be
      efficiently enriched. Suited HSCCC fractions from the three plant oils were
      merged and re-injected into the HSCCC system (purification step). The HSCCC
      purification step provided 6.9 mg campesterol (>= 99%), 2.9 mg brassicasterol (>=
      99%), 0.3mg Delta5-avenasterol (>= 90%), 9.5mg cycloartenol (>= 90%), 3.7 mg 24
      methylene-cycloartanol (>= 99%), and ~ 1mg of an unknown compound (~ 80%)
      isolated from rapeseed and linseed oil. Furthermore, the combined HSCCC
      enrichment and purification of a hydrogenated sterol standard provided two pure
      phytostanols (campestanol >= 99% and sitostanol >= 99%) and several by-products.

PMID- 22481108
TI  - Nano-liquid chromatography coupled with mass spectrometry: separation of
      sulfonamides employing non-porous core-shell particles.
AB  - In this paper, nano-liquid chromatography coupled with mass spectrometry was used
      for the simultaneous determination of 18 sulfonamides. Preliminary experiments
      were carried out to investigate selectivity of three different stationary phases.
      Best results were achieved utilizing a capillary column (100 MUm I.D.) packed in
      our laboratory following the slurry packing procedure with a recent
      commercialized stationary phase, Kinetex((r)) C(18) core-shell. A binary mobile
      phase, consisting of water and acetonitrile and both containing 0.1% (v/v) formic
      acid, was employed in a gradient mode at a low flow rate (190 nL/min). Applying
      these conditions, baseline separation of studied compounds was obtained in about
      35 min. Although sulfathiazole and sulfapyridine were resolved from the other
      drugs, they were not separated from each other. Sensitivity was improved by on
      column focusing evaluating the appropriate sample solvent and establishing the
      maximum injection volume. Comparison between UV and mass spectrometric detection
      was done. Milk samples spiked with sulfonamides were subjected to a rapid pre
      treatment by means of acidic deproteinization followed by solid-phase extraction,
      and analyzed with the developed method. The detection limits obtained in milk
      were in the range of 8-96 MUg/kg, however they were low enough according to the
      regulations set-up by the European Commission. Calibration curves showed good
      linearity (R(2)>0.995) in the studied concentration ranges.

PMID- 22481109
TI  - Optimizing a chromatographic three component separation: a comparison of
      mechanistic and empiric modeling approaches.
AB  - The search for a favorable and robust operating point of a separation process
      represents a complex multi-factor optimization problem. This problem is typically
      tackled by design of experiments (DoE) in the factor space and empiric response
      surface modeling (RSM); however, separation optimizations based on mechanistic
      modeling are on the rise. In this paper, a DoE-RSM-approach and a mechanistic
      modeling approach are compared with respect to their performance and predictive
      power by means of a case study - the optimization of a multicomponent separation
      of proteins in an ion exchange chromatography step with a nonlinear gradient
      (ribonuclease A, cytochrome c and lysozyme on SP Sepharose FF). The results
      revealed that at least for complex problems with low robustness, the performance
      of the DoE-approach is significantly inferior to the performance of the
      mechanistic model. While some influential factors of the system could be detected
      with the DoE-RSM-approach, predictions concerning the peak resolutions were
      mostly inaccurate and the optimization failed. The predictions of the mechanistic
      model for separation results were very accurate. Influences of the experimental
      factors could be quantified and the separation was optimized with respect to
      several objectives. However, the discussion of advantages and disadvantages of
      empiric and mechanistic modeling generates synergies of both methods and leads to
      a new optimization concept, which is promising with respect to an efficient
      employment of high throughput screening data.

PMID- 22481110
TI  - Giant piezoelectric resistance effect of nanoscale zinc oxide tunnel junctions:
      first principles simulations.
AB  - Based on first principles simulations and quantum transport calculations, we have
      investigated in the present work the effect of the mechanical load on transport
      characteristics and the relative physical properties of nanoscale zinc oxide
      (ZnO) tunnel junctions, and verified an intrinsic giant piezoelectric resistance
      (GPR) effect. Our results show that the transport-relevant properties, e.g., the
      piezoelectric potential (piezopotential), built-in electric field, conduction
      band offset and electron transmission probability of the junction etc., can
      obviously be tuned by the applied strain. Accordingly, it is inspiring to find
      that the current-voltage characteristics and tunneling electro-resistance of the
      ZnO tunnel junction can significantly be adjusted with the strain. When the
      applied strain switches from -5% to 5%, an increase of more than 14 times in the
      tunneling current at a bias voltage of 1.1 V can be obtained. Meanwhile, an
      increase of up to 2000% of the electro-resistance ratio with respect to the zero
      strain state can be reached at the same bias voltage and with a 5% compression.
      According to our investigations, the giant piezoelectric resistance effect of
      nanoscale ZnO tunnel junctions exhibits great potential in exploiting tunable
      electronic devices. Furthermore, the methodology of strain engineering revealed
      in this work may shed light on the mechanical manipulations of electronic
      devices. 

PMID- 22481111
TI  - Aerosol residence times and changes in radioiodine-131I and radiocaesium-137 Cs
      activity over Central Poland after the Fukushima-Daiichi Nuclear reactor
      accident.
AB  - The first detectable activities of radioiodine (131)I, and radiocaesium (134)Cs
      and (137)Cs in the air over Central Poland were measured in dust samples
      collected by the ASS-500 station in the period of 21(st) to 24(th) of March,
      2011. However, the highest activity of both fission products, (131)I and (137)Cs:
      8.3 mBq m(-3) and 0.75 mBq m(-3), respectively, were obtained in the samples
      collected on 30(th) March, i.e.~18 days after the beginning of the fission
      products' discharge from the damaged units of the Fukushima Daiichi Nuclear Power
      Plant. The simultaneously determined corrected aerosol residence time for the
      same samples by (210)Pb/(210)Bi and (210)Pb/(210)Po methods was equal to 10 days.
      Additionally, on the basis of the activity ratio of two other natural cosmogenic
      radionuclides, (7)Be and (22)Na in these aerosol samples, it was possible to
      estimate the aerosol residence time at ~150 days for the solid particles coming
      from the stratospheric fallout. These data, as well as the differences in the
      activity size distribution of (7)Be and (131)I in the air particulate matter,
      show, in contrast to the Chernobyl discharge, a negligible input of stratospheric
      transport of Fukushima-released fission products.

PMID- 22481112
TI  - Current opinion in chemical biology.

PMID- 22481113
TI  - Oxomanganese complexes for natural and artificial photosynthesis.
AB  - The oxygen-evolving complex (OEC) of Photosystem II (PSII) is an oxomanganese
      complex that catalyzes water-splitting into O2, protons and electrons. Recent
      breakthroughs in X-ray crystallography have resolved the cuboidal OEC structure
      at 1.9 A resolution, stimulating significant interest in studies of
      structure/function relations. This article summarizes recent advances on studies
      of the OEC along with studies of synthetic oxomanganese complexes for artificial
      photosynthesis. Quantum mechanics/molecular mechanics hybrid methods have enabled
      modeling the S1 state of the OEC, including the ligation proposed by the most
      recent X-ray data where D170 is bridging Ca and the Mn center outside the CaMn3
      core. Molecular dynamics and Monte Carlo simulations have explored the
      structural/functional roles of chloride, suggesting that it regulates the
      electrostatic interactions between D61 and K317 that might be critical for proton
      abstraction. Furthermore, structural studies of synthetic oxomanganese complexes,
      including the [H2O(terpy)MnIII(MU-O)2MnIV(terpy)OH2]3+ (1, terpy=2,2':6',2"
      terpyridine) complex, provided valuable insights on the mechanistic influence of
      carboxylate moieties in close contact with the Mn catalyst during oxygen
      evolution. Covalent attachment of 1 to TiO2 has been achieved via direct
      deposition and by using organic chromophoric linkers. The (III,IV) oxidation
      state of 1 attached to TiO2 can be advanced to (IV,IV) by visible-light
      photoexcitation, leading to photoinduced interfacial electron transfer. These
      studies are particularly relevant to the development of artificial photosynthetic
      devices based on inexpensive materials.

PMID- 22481115
TI  - Superconducting nanofilms: molecule-like pairing induced by quantum confinement.
AB  - Quantum confinement of the perpendicular motion of electrons in single
      crystalline metallic superconducting nanofilms splits the conduction band into a
      series of single-electron subbands. A distinctive feature of such a nanoscale
      multi-band superconductor is that the energetic position of each subband can vary
      significantly with changing nanofilm thickness, substrate material, protective
      cover and other details of the fabrication process. It can occur that the bottom
      of one of the available subbands is situated in the vicinity of the Fermi level.
      We demonstrate that the character of the superconducting pairing in such a
      subband changes dramatically and exhibits a clear molecule-like trend, which is
      very similar to the well-known crossover from the Bardeen-Cooper-Schrieffer
      regime to Bose-Einstein condensation (BCS-BEC) observed in trapped ultracold
      fermions. For Pb nanofilms with thicknesses of 4 and 5 monolayers (MLs) this will
      lead to a spectacular scenario: up to half of all the Cooper pairs nearly
      collapse, shrinking in the lateral size (parallel to the nanofilm) down to a few
      nanometers. As a result, the superconducting condensate will be a coherent
      mixture of almost molecule-like fermionic pairs with ordinary, extended Cooper
      pairs.

PMID- 22481114
TI  - Energy reserve modification in different age groups of Daphnia schoedleri
      (Anomopoda: Daphniidae) exposed to hexavalent chromium.
AB  - Caloric content is a reliable biomaker of effect since it is modified by exposure
      to toxicants that can alter basal metabolism. Since organisms' age modifies how
      energy resources are allocated and modifies the activity of antioxidant enzymes,
      the response to toxic agents could be altered with age. Seven age groups of
      Daphnia schoedleri (0, 3, 5, 7, 14, 21, and 28-day-old) were exposed for 24h to
      two sublethal concentrations of Cr(VI): 1/25 and 1/5 of the 48 h EC(50) of each
      age group, to determine the age at which susceptibility to Cr(VI) is highest. To
      evaluate energy content, carbohydrate, protein and lipid reserves were quantified
      and antioxidant enzymes activity was assessed (SOD, CAT, GPx, and GR).
      Furthermore, an integrative approach was applied to evaluate both sets of
      responses and interpret them as a whole in a simply visual way, achieved by the
      integrated biomarker response approach. Results indicate that Cr(VI) induced
      significant differences in all age groups. Seven and 14-day-old organisms were
      exposed to the highest concentrations (based on their EC50) and showed greater
      tolerance to this metal. Susceptibility to the toxicant was highest in younger
      specimens in which energy requirements are greater due to high growth rates
      (basal metabolism), as a result of which more energy reserves are expended to
      satisfy demands in terms of growth and response to toxicants.

PMID- 22481116
TI  - Primary cutaneous anaplastic large cell lymphoma arising from a burn scar.

PMID- 22481117
TI  - Hemodynamic effects of aortocaval compression and uterine contractions in a
      parturient with left ventricular outflow tract obstruction.

PMID- 22481118
TI  - Degrees of reality: airway anatomy of high-fidelity human patient simulators and
      airway trainers.
AB  - BACKGROUND: Human patient simulators and airway training manikins are widely used
      to train airway management skills to medical professionals. Furthermore, these
      patient simulators are employed as standardized "patients" to evaluate airway
      devices. However, little is known about how realistic these patient simulators
      and airway-training manikins really are. This trial aimed to evaluate the upper
      airway anatomy of four high-fidelity patient simulators and two airway trainers
      in comparison with actual patients by means of radiographic measurements. The
      volume of the pharyngeal airspace was the primary outcome parameter. METHODS:
      Computed tomography scans of 20 adult trauma patients without head or neck
      injuries were compared with computed tomography scans of four high-fidelity
      patient simulators and two airway trainers. By using 14 predefined distances, two
      cross-sectional areas and three volume parameters of the upper airway, the
      manikins' similarity to a human patient was assessed. RESULTS: The pharyngeal
      airspace of all manikins differed significantly from the patients' pharyngeal
      airspace. The HPS Human Patient Simulator (METI(r), Sarasota, FL) was the most
      realistic high-fidelity patient simulator (6/19 [32%] of all parameters were
      within the 95% CI of human airway measurements). CONCLUSION: The airway anatomy
      of four high-fidelity patient simulators and two airway trainers does not reflect
      the upper airway anatomy of actual patients. This finding may impact airway
      training and confound comparative airway device studies.

PMID- 22481119
TI  - OsGA20ox1, a candidate gene for a major QTL controlling seedling vigor in rice.
AB  - Seedling vigor is among the major determinants of stable stand establishment in
      direct-seeded rice (Oryza sativa L.) in temperate regions. Quantitative trait
      loci (QTL) for seedling vigor were identified using 250 recombinant inbred lines
      (RILs) derived from a cross between two japonica rice cultivars Kakehashi and
      Dunghan Shali. Seedling heights measured at 14 days after sowing were 20.3 and
      29.4 cm for Kakehashi and Dunghan Shali, respectively. For the RILs, the height
      ranged from 14.1 to 31.7 cm. Four putative QTLs associated with seedling height
      were detected. qPHS3-2, the major QTL that was located on the long arm of
      chromosome 3, accounted for 26.2 % of the phenotypic variance. Using progeny of
      the near isogenic lines (NILs) produced by the backcross introduction of a
      chromosome segment carrying this major QTL into an elite cultivar Iwatekko, we
      fine-mapped qPHS3-2 to a 81-kb interval between two markers, ID_CAPS_01 and
      RM16227. Within this mapped region, we identified the gene OsGA20ox1, which is
      related to gibberellin (GA) biosynthesis. The relative expression levels of
      GA20ox1 in seedlings of Dunghan Shali and NILs were higher than that of Iwatekko.
      Concomitantly, the amount of endogenous active GA was higher in Dunghan Shali and
      the NILs compared to the level detected in Iwatekko. These results indicate that
      OsGA20ox1 is a strong candidate gene for major QTL controlling seedling vigor in
      rice.

PMID- 22481120
TI  - QTL analysis of soybean seed weight across multi-genetic backgrounds and
      environments.
AB  - Seed weight, measured as mass per seed, is an important yield component of
      soybean and is generally positively correlated with seed yield (Burton et al,
      Crop Sci 27:1093, 1987). In previous reports, quantitative trait loci (QTL)
      associated with seed weight, were identified in single genetic background. The
      objective of the present study was to identify QTL and epistatic QTL underlying
      soybean seed weight in three RIL populations (with one common male parent
      'Hefeng25') and across three different environments. Overall, 18, 11, and 17 seed
      weight QTL were identified in HC ('Hefeng25' * 'Conrad'), HM ('Hefeng25' * 'Maple
      Arrow'), and HB ('Hefeng25' * 'Bayfield') populations, respectively. The amount
      of phenotypic variation explained by a single QTL underlying seed weight was
      usually less than 10 %. The environment and background-independent QTL often had
      higher additive (a) effects. In contrast, the environment or background-dependent
      QTL were probably due to weak expression of QTL. QTL by environment interaction
      effects were in the opposite direction of a effects and/or epistasis effects.
      Four QTL and one QTL could be identified (2.0 < LOD < 9.06) in the HC and HB
      populations, respectively, across three environments (swHCA2-1, swHCC2-1, swHCD1b
      1, swHCA2-2 (linked to Satt233, Satt424, Satt460, Satt428, respectively) and
      swHBA1-1(Satt449). Seven QTL could be identified in all three RIL populations in
      at least one location. Two QTL could be identified in the three RIL populations
      across three environments. These two QTL may have greater potential for use in
      marker-assisted selection of seed weight in soybean.

PMID- 22481121
TI  - Impact of selective genotyping in the training population on accuracy and bias of
      genomic selection.
AB  - Estimating marker effects based on routinely generated phenotypic data of
      breeding programs is a cost-effective strategy to implement genomic selection.
      Truncation selection in breeding populations, however, could have a strong impact
      on the accuracy to predict genomic breeding values. The main objective of our
      study was to investigate the influence of phenotypic selection on the accuracy
      and bias of genomic selection. We used experimental data of 788 testcross
      progenies from an elite maize breeding program. The testcross progenies were
      evaluated in unreplicated field trials in ten environments and fingerprinted with
      857 SNP markers. Random regression best linear unbiased prediction method was
      used in combination with fivefold cross-validation based on genotypic sampling.
      We observed a substantial loss in the accuracy to predict genomic breeding values
      in unidirectional selected populations. In contrast, estimating marker effects
      based on bidirectional selected populations led to only a marginal decrease in
      the prediction accuracy of genomic breeding values. We concluded that
      bidirectional selection is a valuable approach to efficiently implement genomic
      selection in applied plant breeding programs.

PMID- 22481123
TI  - NO dissociation on Cu(111) and Cu2O(111) surfaces: a density functional theory
      based study.
AB  - NO dissociation on Cu(111) and Cu(2)O(111) surfaces is investigated using spin
      polarized density functional theory. This is to verify the possibility of using
      Cu-based catalyst for NO dissociation which is the rate limiting step for the
      NO(x) reduction process. The dissociation of molecularly adsorbed NO on the
      surface is activated for both cases. However, from the reaction path of the NO
      Cu(2)O(111) system, the calculated transition state lies below the reference
      energy which indicates the possibility of dissociation. For the NO-Cu(111)
      system, the reaction path shows that NO desorption is more likely to occur. The
      geometric and electronic structure of the Cu(2)O(111) surface indicates that the
      surface Cu atoms stabilize themselves with reference to the O atom in the
      subsurface. The interaction results in modification of the electronic structure
      of the surface Cu atoms of Cu(2)O(111) which greatly affects the adsorption and
      dissociation of NO. This phenomenon further explains the obtained differences in
      the dissociation pathways of NO on the surfaces.

PMID- 22481122
TI  - Genome-wide analysis of cell wall-related genes in Tuber melanosporum.
AB  - A genome-wide inventory of proteins involved in cell wall synthesis and
      remodeling has been obtained by taking advantage of the recently released genome
      sequence of the ectomycorrhizal Tuber melanosporum black truffle. Genes that
      encode cell wall biosynthetic enzymes, enzymes involved in cell wall
      polysaccharide synthesis or modification, GPI-anchored proteins and other cell
      wall proteins were identified in the black truffle genome. As a second step,
      array data were validated and the symbiotic stage was chosen as the main focus.
      Quantitative RT-PCR experiments were performed on 29 selected genes to verify
      their expression during ectomycorrhizal formation. The results confirmed the
      array data, and this suggests that cell wall-related genes are required for
      morphogenetic transition from mycelium growth to the ectomycorrhizal branched
      hyphae. Labeling experiments were also performed on T. melanosporum mycelium and
      ectomycorrhizae to localize cell wall components.

PMID- 22481124
TI  - A relation between TGF-beta and mast cell tryptase in experimental emphysema
      models.
AB  - Chronic obstructive pulmonary disease (COPD) is a multicomponent disease
      characterized by emphysema and/or chronic bronchitis. The aim of this study was
      to investigate the effect of cigarette smoke exposure on mast cells and mast cell
      function in vitro and in vivo in order to get further insight in the role of mast
      cells in the pathogenesis of emphysema. Cigarette smoke conditioned medium (CSM)
      induced the expression of mast cell tryptase (MMCP-6) in primary cultured mast
      cells. This tryptase expression was caused by the CSM-stimulated production of
      TGF-beta in culture and neutralization of TGF-beta suppressed the CSM-induced
      expression of tryptase in mast cells. An increase in mast cell tryptase
      expression was also found in an experimental model for emphysema. Exposure of
      mice to cigarette smoke increased the number of mast cells in the airways and the
      expression of mast cell tryptase. In accordance with the in vitro findings, TGF
      beta in bronchoalveolar lavage fluid of smoke-exposed animals was significantly
      increased. Our study indicates that mast cells may be a source of TGF-beta
      production after cigarette smoke exposure and that in turn TGF-beta may change
      the tryptase expression in mast cells.

PMID- 22481125
TI  - Effects of single-fracture aperture statistics on entrapment, dissolution and
      source depletion behavior of dense non-aqueous phase liquids.
AB  - Understanding of the entrapment and dissolution behavior of dense non-aqueous
      phase liquids (DNAPLs) in single fractures is important for modeling contaminant
      flux generation from fractured sites. Here a systematic numerical study is
      presented to investigate the effect of fracture aperture statistics on DNAPL
      migration, entrapment and dissolution within individual, variable-aperture
      fractures. Both fractures with open and closed bottom boundaries were considered.
      For the simulation a continuum-based two-phase model was used with a capillary
      pressure function which calculates the entry pressure based on the local
      aperture. Prior to application the model was compared against the invasion
      percolation approach and found more suitable for the present study, in particular
      as it allows a more versatile presentation of boundary conditions. The results
      showed that increasing aperture standard deviation and/or decreasing correlation
      length lead to larger amounts of entrapped DNAPL (due to the fact that larger
      standard deviation produces more distinct contrast between small and large
      aperture regions and the fact that longer correlation length provides more
      possible channels through the fracture) as well as larger maximum and average
      sizes of DNAPL blobs, and subsequently lead to longer times for complete
      dissolution. To understand the relationship between the solute flux and the
      remaining mass, a simplified source depletion function which links the outflow
      concentration to the DNAPL saturation was found adequate to describe the
      dissolution process for the case where the bottom boundary is open for DNAPL
      migration and thus the DNAPL does not accumulate to form a pool. The parameters
      in this function were not very sensitive to variations in correlation length but
      were sensitive to aperture standard deviation. The same average entrapped DNAPL
      saturation produced considerably smaller solute concentrations in cases with
      larger aperture variability due to the larger average size of DNAPL blobs (i.e.,
      smaller contact area for DNAPL dissolution). Boundary conditions had a
      significant impact on DNAPL entrapment and dissolution. A closed boundary at the
      bottom led to DNAPL pooling (i.e., large continuous blobs) which causes
      significant tailing in the dissolution breakthrough curve due to water bypassing.

PMID- 22481126
TI  - Effect of shoulder pain on shoulder kinematics during weight-bearing tasks in
      persons with spinal cord injury.
AB  - OBJECTIVE: To assess 3-dimensional scapulothoracic and glenohumeral kinematics
      between subjects with spinal cord injury and disease (SCI/D) with and without
      shoulder pain during a weight-relief raise and transfer task. DESIGN: Case
      control, repeated-measures analysis of variance. SETTING: Movement analysis
      laboratory. PARTICIPANTS: Subjects (N=43; 23 with clinical signs of impingement
      and 20 without) between 21 and 65 years of age, at least 1 year after SCI/D
      (range, 1-43y) resulting in American Spinal Injury Association Impairment Scale
      T2 motor neurologic level or below, and requiring the full-time use of a manual
      wheelchair. INTERVENTIONS: Weight-relief raises and transfer tasks. MAIN OUTCOME
      MEASURES: An electromagnetic tracking system acquired 3-dimensional position and
      orientation of the thorax, scapula, and humerus. Dependent variables included
      angular values for scapular upward and downward rotation, posterior and anterior
      tilt, and internal and external rotation relative to the thorax, and glenohumeral
      internal and external rotation relative to the scapula. The mean of 3 trials was
      collected, and angular values were compared at 3 distinct phases of the weight
      relief raise and transfer activity. Comparisons were also made between transfer
      direction (lead vs trail arm) and across groups. RESULTS: Key findings include
      significantly increased scapular upward rotation for the pain group during
      transfer (P=.03). Significant group differences were found for the trailing arm
      at the lift pivot (phase 2) of the transfer, with the pain group having greater
      anterior tilt (mean difference +/- SE, 5.7 degrees +/-2.8 degrees ). The
      direction of transfer also influenced kinematics at the different phases of the
      activity. CONCLUSIONS: Potentially detrimental magnitude and direction of
      scapular and glenohumeral kinematics during weight-bearing tasks may pose
      increased risk for shoulder pain or injury in persons with SCI/D. Consideration
      should be given to rehabilitation strategies that promote favorable scapular
      kinematics and glenohumeral external rotation.

PMID- 22481127
TI  - Comparative study of short forms of the Tampa Scale for Kinesiophobia: fear of
      movement in a surgical spine population.
AB  - OBJECTIVE: To compare the factor structure of 6 short forms of the Tampa Scale
      for Kinesiophobia (TSK) by means of confirmatory factor analysis in patients
      after spinal surgery for degenerative conditions. DESIGN: A cross-sectional
      survey study. SETTING: University-based surgical clinic. PARTICIPANTS: Adults
      (N=137) treated by spinal surgery for a degenerative condition (ie, spinal
      stenosis, spondylosis with or without myelopathy, and spondylolisthesis).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Patients completed the TSK
      within 3 months of hospital discharge. RESULTS: Confirmatory factor analysis
      demonstrated that the 2-factor models of the TSK-13 and TSK-11 had a reasonable
      fit for the data, with internal consistency values >.70. A 1-factor TSK-4 (items
      3, 6, 7, and 11) demonstrated an excellent fit for the data, but an adequate
      internal consistency was not maintained. A poor fit was noted for the 1-factor
      models of the TSK-13 and TSK-11, and a 4-item TSK (items 1, 2, 9, and 11).
      CONCLUSIONS: The current study provides further evidence that specific short-form
      versions of the TSK may be useful for assessing fear of movement in surgical
      populations. Results support the measurement of fear of movement using the 2
      factor, 13- and 11-item versions of the TSK in patients after spinal surgery. A
      TSK-4 (items 3, 6, 7, and 11) offers a promising alternative to the TSK-13 and
      TSK-11. However, further research is needed to test the validity and reliability
      of the TSK-4 in patients undergoing spinal surgery in order to support its use in
      a clinical environment. Researchers and clinicians interested in a shorter
      measure of fear of movement should consider using the TSK-11.

PMID- 22481128
TI  - BRCA genetic testing of individuals from families with low prevalence of cancer:
      experiences of carriers and implications for population screening.
AB  - PURPOSE: BRCA genes are associated with hereditary breast and ovarian cancers.
      Guidelines worldwide currently recommend BRCA genetic testing in asymptomatic
      individuals only if they belong to "high-risk" families. However, population
      screening for BRCA1/2 may be the logical next step in populations with a high
      prevalence of founder mutations, such as Ashkenazi Jews. This study aimed to
      explore (i) the impact of a positive BRCA genetic test result on individuals who
      have neither a personal history nor a familial history of cancer and (ii) their
      attitudes toward the concept of population screening. METHODS: Semistructured in
      depth interviews were carried out with 14 Ashkenazi Jewish women who were
      asymptomatic BRCA carriers and who belonged to families with low prevalence of
      cancer. RESULTS: Three main findings emerged: (i) having no family history of
      cancer was a source of optimism but also confusion; (ii) engaging in intensified
      medical surveillance and undergoing preventive procedures was perceived as health
      promoting but also tended to induce a sense of physical and psychological
      vulnerability; and (iii) there was overall support for BRCA population screening,
      with some reservations. CONCLUSION: Women belonging to low-cancer-prevalence
      families within a "high-risk" ethnic community view BRCA genetic testing
      positively despite the difficulties entailed, because it allows prevention or
      early detection of cancer. However, implementing a BRCA population screening
      program should be carried out with proper pre- and post-testing preparation and
      support for the individuals undergoing testing.

PMID- 22481129
TI  - Communicating new knowledge on previously reported genetic variants.
AB  - Genetic tests often identify variants whose significance cannot be determined at
      the time they are reported. In many situations, it is critical that clinicians be
      informed when new information emerges on these variants. It is already extremely
      challenging for laboratories to provide these updates. These challenges will grow
      rapidly as an increasing number of clinical genetic tests are ordered and as the
      amount of patient DNA assayed per test expands; the challenges will need to be
      addressed before whole-genome sequencing is used on a widespread
      basis.Information technology infrastructure can be useful in this context. We
      have deployed an infrastructure enabling clinicians to receive knowledge updates
      when a laboratory changes the classification of a variant. We have gathered
      statistics from this deployment regarding the frequency of both variant
      classification changes and the effects of these classification changes on
      patients. We report on the system's functionality as well as the statistics
      derived from its use.Genet Med advance online publication 5 April 2012.

PMID- 22481130
TI  - Stakeholder assessment of the evidence for cancer genomic tests: insights from
      three case studies.
AB  - PURPOSE: Insufficient evidence on the net benefits and harms of genomic tests in
      real-world settings is a translational barrier for genomic medicine.
      Understanding stakeholders' assessment of the current evidence base for clinical
      practice and coverage decisions should be a critical step in influencing
      research, policy, and practice. METHODS: Twenty-two stakeholders participated in
      a workshop exploring the evidence of genomic tests for clinical and coverage
      decision making. Stakeholders completed a survey prior to and during the meeting.
      They also discussed if they would recommend for or against current clinical use
      of each test. RESULTS: At baseline, the level of confidence in the clinical
      validity and clinical utility of each test varied, although the group expressed
      greater confidence for epidermal growth factor receptor mutation and Lynch
      syndrome testing than for Oncotype DX. Following the discussion, survey results
      reflected even less confidence for Oncotype DX, intermediate levels of confidence
      for [corrected] epidermal growth factor receptor mutation testing and stable
      levels of confidence [corrected] for Lynch syndrome testing. The majority of
      stakeholders would consider clinical use for all three tests, but under the
      conditions of additional research or a shared clinical decision-making approach.
      CONCLUSION: Stakeholder engagement in unbiased settings is necessary to
      understand various perspectives about evidentiary thresholds in genomic medicine.
      Participants recommended the use of various methods for evidence generation and
      synthesis.

PMID- 22481131
TI  - Decision analysis, economic evaluation, and newborn screening: challenges and
      opportunities.
AB  - The number of conditions included in newborn screening panels has increased
      rapidly in the United States during the past decade, and many more conditions are
      under consideration for addition to state panels. The rare nature of candidate
      conditions for newborn screening makes their evaluation challenging. The scarcity
      of data on the costs of screening, follow-up, treatment, and long-term disability
      must be addressed to improve the evaluation process for nominated conditions.
      Decision analyses and economic evaluations can help inform policy decisions for
      newborn screening programs by providing a systematic approach to synthesizing
      available evidence and providing projected estimates of long-term clinical and
      economic outcomes when long-term data are not available. In this review, we
      outline the types of data required for the development of decision analysis and
      cost-effectiveness models for newborn screening programs and discuss the
      challenges faced when applying these methods in the arena of newborn screening to
      help inform policy decisions.Genet Med advance online publication 5 April 2012.

PMID- 22481133
TI  - Bone mineral density in glycogen storage disease type Ia and Ib.
AB  - Purpose:The aim of this study was to characterize the pathogenesis of low bone
      mineral density in glycogen storage disease type Ia and Ib.Methods:A
      retrospective chart review performed at the University of Florida Glycogen
      Storage Disease Program included patients with glycogen storage disease type Ia
      and Ib for whom dual-energy X-ray absorptiometry analysis was performed. A Z
      score less than -2 SD was considered low. Analysis for association of bone
      mineral density with age, gender, presence of complications, mean triglyceride
      and 25-hydroxyvitamin D concentrations, erythrocyte sedimentation rate, duration
      of granulocyte colony-stimulating factor therapy, and history of corticosteroid
      use was performed.Results:In glycogen storage disease Ia, 23/42 patients (55%)
      had low bone mineral density. Low bone mineral density was associated with other
      disease complications (P = 0.02) and lower mean serum 25-hydroxyvitamin D
      concentration (P = 0.03). There was a nonsignificant trend toward lower mean
      triglyceride concentration in the normal bone mineral density group (P = 0.1).In
      patients with glycogen storage disease type Ib, 8/12 (66.7%) had low bone mineral
      density. We did not detect an association with duration of granulocyte colony
      stimulating factor therapy (P = 0.68), mean triglyceride level (P = 0.267),
      erythrocyte sedimentation rate (P = 0.3), or 25-hydroxyvitamin D (P = 0.63)
      concentration, and there was no evidence that corticosteroid therapy was
      associated with lower bone mineral density (P = 1).Conclusion:In glycogen storage
      disease type Ia, bone mineral density is associated with other complications and
      25-hydroxyvitamin D status. In glycogen storage disease type Ib, bone mineral
      density was not associated with any covariates analyzed, suggesting
      multifactorial etiology or reflecting a small sample.Genet Med advance online
      publication 5 April 2012.

PMID- 22481132
TI  - Patients' understanding of and responses to multiplex genetic susceptibility test
      results.
AB  - PURPOSE: Examination of patients' responses to direct-to-consumer genetic
      susceptibility tests is needed to inform clinical practice. This study examined
      patients' recall and interpretation of, and responses to, genetic susceptibility
      test results provided directly by mail. METHODS: This observational study had
      three prospective assessments (before testing, 10 days after receiving results,
      and 3 months later). Participants were 199 patients aged 25-40 years who received
      free genetic susceptibility testing for eight common health conditions. RESULTS:
      More than 80% of the patients correctly recalled their results for the eight
      health conditions. Patients were unlikely to interpret genetic results as
      deterministic of health outcomes (mean = 6.0, s.d. = 0.8 on a scale of 1-7, 1
      indicating strongly deterministic). In multivariate analysis, patients with the
      least deterministic interpretations were white (P = 0.0098), more educated (P =
      0.0093), and least confused by results (P = 0.001). Only 1% talked about their
      results with a provider. CONCLUSION: Findings suggest that most patients will
      correctly recall their results and will not interpret genetics as the sole cause
      of diseases. The subset of those confused by results could benefit from
      consultation with a health-care provider, which could emphasize that health
      habits currently are the best predictors of risk. Providers could leverage
      patients' interest in genetic tests to encourage behavior changes to reduce
      disease risk.

PMID- 22481135
TI  - Colorectal cancer risk is not associated with increased levels of homozygosity in
      Saudi Arabia.
AB  - Purpose:Runs of homozygosity (ROHs) represent a measure of the extent of
      autozygosity and are correlated with the extent of inbreeding. Recently, it has
      been suggested that ROHs may contribute to the risk of colorectal cancer (CRC).
      The high rate of consanguinity and CRC in the Saudi population prompted us to
      test the role of autozygosity in the CRC risk.Methods:We compared 48 Saudi CRC
      patients to 100 ethnically matched controls, processed on the Affymetrix 250K
      StyI SNP GeneChip platform and analyzed using the plink package.Results:We could
      find no evidence of a significant relationship between autozygosity and CRC
      risk.Conclusion:The negative results in our study add additional significance to
      what has been previously reported in literature, as this is the first study to
      address these questions in an inbred population. Our subgroup analysis of
      patients with microsatellite unstable-positive tumors as compared with other
      groups did not significantly change our results. Although these results do not
      rule out the presence of recessively acting CRC-predisposing genes in a small
      percentage of patients, which our relatively small sample size could not capture,
      they suggest that such genes are unlikely to account for the disturbingly high
      incidence of CRC in our consanguineous population.Genet Med advance online
      publication 5 April 2012.

PMID- 22481134
TI  - Toward modernizing the systematic review pipeline in genetics: efficient updating
      via data mining.
AB  - PURPOSE: The aim of this study was to demonstrate that modern data mining tools
      can be used as one step in reducing the labor necessary to produce and maintain
      systematic reviews. METHODS: We used four continuously updated, manually curated
      resources that summarize MEDLINE-indexed articles in entire fields using
      systematic review methods (PDGene, AlzGene, and SzGene for genetic determinants
      of Parkinson disease, Alzheimer disease, and schizophrenia, respectively; and the
      Tufts Cost-Effectiveness Analysis (CEA) Registry for cost-effectiveness
      analyses). In each data set, we trained a classification model on citations
      screened up until 2009. We then evaluated the ability of the model to classify
      citations published in 2010 as "relevant" or "irrelevant" using human screening
      as the gold standard. RESULTS: Classification models did not miss any of the 104,
      65, and 179 eligible citations in PDGene, AlzGene, and SzGene, respectively, and
      missed only 1 of 79 in the CEA Registry (100% sensitivity for the first three and
      99% for the fourth). The respective specificities were 90, 93, 90, and 73%. Had
      the semiautomated system been used in 2010, a human would have needed to read
      only 605/5,616 citations to update the PDGene registry (11%) and 555/7,298 (8%),
      717/5,381 (13%), and 334/1,015 (33%) for the other three databases. CONCLUSION:
      Data mining methodologies can reduce the burden of updating systematic reviews,
      without missing more papers than humans.

PMID- 22481136
TI  - Phototropism of Arabidopsis thaliana in microgravity and fractional gravity on
      the International Space Station.
AB  - While there is a great deal of knowledge regarding plant growth and development
      in microgravity aboard orbiting spacecraft, there is little information available
      about these parameters in reduced or fractional gravity conditions (less than the
      nominal 1g on Earth). Thus, in these experiments using the European Modular
      Cultivation System on the International Space Station, we studied the interaction
      between phototropism and gravitropism in the WT and mutants of phytochrome A and
      B of Arabidopis thaliana. Fractional gravity and the 1 g control were provided by
      centrifuges in the spaceflight hardware, and unidirectional red and blue
      illumination followed a white light growth period in the time line of the space
      experiments. The existence of red-light-based positive phototropism in hypocotyls
      of seedlings that is mediated by phytochrome was confirmed in these microgravity
      experiments. Fractional gravity studies showed an attenuation of red-light-based
      phototropism in both roots and hypocotyls of seedlings occurring due to
      gravitational accelerations ranging from 0.l to 0.3 g. In contrast, blue-light
      negative phototropism in roots, which was enhanced in microgravity compared with
      the 1g control, showed a significant attenuation at 0.3 g. In addition, our
      studies suggest that the well-known red-light enhancement of blue-light-induced
      phototropism in hypocotyls is likely due to an indirect effect by the attenuation
      of gravitropism. However, red-light enhancement of root blue-light-based
      phototropism may occur via a more direct effect on the phototropism system
      itself, most likely through the phytochrome photoreceptors. To our knowledge,
      these experiments represent the first to examine the behavior of flowering plants
      in fractional or reduced gravity conditions.

PMID- 22481137
TI  - Discovery and profiling of novel and conserved microRNAs during flower
      development in Carya cathayensis via deep sequencing.
AB  - Hickory (Carya cathayensis Sarg.) is an economically important woody plant in
      China, but its long juvenile phase delays yield. MicroRNAs (miRNAs) are critical
      regulators of genes and important for normal plant development and physiology,
      including flower development. We used Solexa technology to sequence two small RNA
      libraries from two floral differentiation stages in hickory to identify miRNAs
      related to flower development. We identified 39 conserved miRNA sequences from
      114 loci belonging to 23 families as well as two novel and ten potential novel
      miRNAs belonging to nine families. Moreover, 35 conserved miRNA*s and two novel
      miRNA*s were detected. Twenty miRNA sequences from 49 loci belonging to 11
      families were differentially expressed; all were up-regulated at the later stage
      of flower development in hickory. Quantitative real-time PCR of 12 conserved
      miRNA sequences, five novel miRNA families, and two novel miRNA*s validated that
      all were expressed during hickory flower development, and the expression patterns
      were similar to those detected with Solexa sequencing. Finally, a total of 146
      targets of the novel and conserved miRNAs were predicted. This study identified a
      diverse set of miRNAs that were closely related to hickory flower development and
      that could help in plant floral induction.

PMID- 22481138
TI  - Arsenal of elevated defense proteins fails to protect tomato against Verticillium
      dahliae.
AB  - Although the hypersensitive reaction in foliar plant diseases has been
      extensively described, little is clear regarding plant defense strategies in
      vascular wilt diseases affecting numerous economically important crops and trees.
      We have examined global genetic responses to Verticillium wilt in tomato
      (Lycopersicon esculentum Mill.) plants differing in Ve1 resistance alleles.
      Unexpectedly, mRNA analyses in the susceptible plant (Ve1-) based on the
      microarrays revealed a very heroic but unsuccessful systemic response involving
      many known plant defense genes. In contrast, the response is surprisingly low in
      plants expressing the Ve1+ R-gene and successfully resisting the pathogen.
      Similarly, whole-cell protein analyses, based on 2D gel electrophoresis and mass
      spectrometry, demonstrate large systemic increases in a variety of known plant
      defense proteins in the stems of susceptible plants but only modest changes in
      the resistant plant. Taken together, the results indicate that the large systemic
      increases in plant defense proteins do not protect the susceptible plant. Indeed,
      since a number of the highly elevated proteins are known to participate in the
      plant hypersensitive response as well as natural senescence, the results suggest
      that some or all of the disease symptoms, including ultimate plant death,
      actually may be the result of this exaggerated plant response.

PMID- 22481139
TI  - Metastable phase formation and structural evolution of epitaxial graphene grown
      on SiC(100) under a temperature gradient.
AB  - Multilayer epitaxial graphene was obtained from a 6H-SiC(001) substrate subjected
      to a temperature gradient from 1250 to 1450  degrees C. Scanning tunneling
      microscopy and x-ray diffraction were used to identify the structure and
      morphology of the surface, from which the formation of a metastable phase was
      inferred. By a comparison between microscopy and diffraction data, we report the
      appearance of misoriented Si-doped graphene in cold regions (1250  degrees C) of
      the substrate. This metastable phase occurs in domains where silicon sublimation
      is incomplete and it coexists with small domains of epitaxial graphene. At 1350 
      degrees C this phase disappears and one observes complete graphene-like layers
      (although misoriented), where rotational registry between the underlying
      epitaxial graphene and additional layers is absent. At 1450  degrees C the
      stacking among layers is established and the formation of highly oriented single
      crystalline graphite is complete. The stability of this Si-rich metastable phase
      at 1250  degrees C was confirmed by first-principles calculations based on the
      density functional theory.

PMID- 22481141
TI  - Diagnosis of henipavirus infection: current capabilities and future directions.
AB  - Since the last major review on diagnosis of henipavirus infection about a decade
      ago, significant progress has been made in many different areas of test
      development, especially in the development of molecular tests using real-time PCR
      and many novel serological test platforms. In addition to provide an updated
      review of the current test capabilities, this review also identifies key future
      challenges in henipavirus diagnosis.

PMID- 22481140
TI  - Immunization strategies against henipaviruses.
AB  - Hendra virus and Nipah virus are recently discovered and closely related emerging
      viruses that now comprise the genus henipavirus within the sub-family
      Paramyxoviridae and are distinguished by their broad species tropism and in
      addition to bats can infect and cause fatal disease in a wide variety of
      mammalian hosts including humans. The high mortality associated with human and
      animal henipavirus infections has highlighted the importance and necessity of
      developing effective immunization strategies. The development of suitable animal
      models of henipavirus infection and pathogenesis has been critical for testing
      the efficacy of potential therapeutic approaches. Several henipavirus challenge
      models have been used and recent successes in both active and passive
      immunization strategies against henipaviruses have been reported which have all
      targeted the viral envelope glycoproteins.

PMID- 22481142
TI  - Shape-controlled synthesis and characterization of cobalt oxides hollow spheres
      and octahedra.
AB  - We demonstrated that single-crystalline cobalt monoxide (CoO) hollow spheres and
      octahedra could be selectively synthesized via thermal decomposition of
      cobalt(II) acetylacetonate in 1-octadecene solvent in the presence of oleic acid
      and oleylamine. The morphologies and sizes of as-prepared CoO nanocrystals could
      be controlled by adjusting the reaction parameters. Cobalt oxide (Co(3)O(4))
      hollow spheres and octahedra could also be selectively obtained via calcination
      method using corresponding CoO hollow spheres and octahedra as precursors. The
      morphology, size and structure of the final products were investigated in detail
      by XRD, SEM, TEM, HRTEM, DSC, TG, and XPS. The results revealed that the
      electrochemical performance of cobalt oxide hollow spheres is much better than
      that of cobalt oxide octahedra, which may be related to the degree of
      crystallinity, size, and morphology of cobalt oxides.

PMID- 22481143
TI  - Carotid intima media thickness in patients with sporadic idiopathic
      hypoparathyroidism: a pilot study.
AB  - Alteration in calcium and phosphate levels predisposes to increase in carotid
      intima media thickness (CIMT) as in chronic kidney disease. However, information
      on CIMT changes is lacking in patients with sporadic idiopathic
      hypoparathyroidism (SIH) which is also a disorder of altered calcium and
      phosphate levels and hence, we planned this case-control study. In this study, we
      compared CIMT in 18 consecutive patients of SIH, with age and sex matched healthy
      subjects. CIMT was measured by B-mode ultrasonography by a single trained
      operator blinded to subject's details. CIMT values in patients with SIH were
      significantly higher than healthy subjects (0.63 +/- 0.06 mm vs 0.47 +/- 0.07 mm,
      p<0.001). Despite, healthy subjects had higher body mass index, higher low
      density lipoprotein cholesterol and fasting plasma glucose, CIMT was higher in
      subjects with SIH. Neither clinical nor biochemical parameters correlated with
      CIMT in patients with SIH except age. In conclusion, sporadic idiopathic
      hypoparathyroidism is associated with increased CIMT but biochemical parameters
      do not correlate with CIMT.

PMID- 22481145
TI  - Fertility differences among developing countries: are they still related to
      family planning program efforts and social settings?
AB  - CONTEXT: In many developing countries, fertility has declined steadily in recent
      decades, while the average strength of family planning programs has increased and
      social conditions have improved. However, it is unclear whether the synergistic
      effect of family planning programs and social settings on fertility, first
      identified in the 1970s, still holds. METHODS: Data from 40 developing countries
      in which Demographic and Health Surveys were conducted in 2003-2010 were used to
      examine associations among socioeconomic conditions, family planning program
      effort strength and fertility. Cross-tabulations and multiple regression analyses
      were conducted. RESULTS: Variation among countries in scores on the Family
      Planning Program Effort Index, but not on the Human Development Index, has
      diminished since the 1970s. On average, fertility levels were lower among
      countries with better social settings or stronger family planning programs than
      among those with poorer settings or weaker programs; they were lowest in the
      presence of both good social settings and strong programs. In addition, fertility
      was positively associated with infant mortality and negatively associated with
      female education, but not associated with poverty. About half of the 2.3-birth
      difference in fertility between countries in Sub-Saharan Africa and those
      elsewhere can be attributed to differences in program efforts and social
      settings. CONCLUSIONS: Policies focused on improving levels of female education,
      reducing infant mortality and improving family planning services can be expected
      to have mutually reinforcing effects on fertility decline.

PMID- 22481144
TI  - Multiple deprivations and maternal care in India.
AB  - CONTEXT: Research on inequalities in the utilization of maternal health care
      services is often confined to only the economic domain. Individuals and families
      living in acute poverty may simultaneously experience multiple dimensions of
      deprivation, which together may obstruct their access to basic health services.
      It is important to examine the linkages between multiple deprivations and
      maternal health care. METHODS: Data from the 2005-2006 Indian National Family
      Health Survey were used to examine ever-married women's receipt of antenatal
      care, medical assistance during delivery and postnatal care services across three
      dimensions of deprivation: education, wealth and health. Bivariate analyses,
      principal component analyses and binomial logistic regression analyses were
      conducted. RESULTS: Thirty-two percent of ever-married Indian women reported
      being deprived in one of the three dimensions, 18% in two and 7% in all three;
      43% were deprived in none. Women deprived in all three dimensions were less
      likely than those not deprived in any to have received antenatal care (predicted
      probabilities, 0.3 vs. 0.8) or postnatal care (0.2 vs. 0.7); the likelihood that
      a birth occurred with medical assistance was smaller for women deprived in three
      dimensions than for those deprived in none (0.2 vs. 0.8). These patterns held
      true for all of the larger Indian states. Differentials in utilization of
      maternal care services across deprivation levels were higher in states where
      service coverage was low and lower in states where service coverage was high.
      CONCLUSION: More research is needed to understand how multiple deprivations are
      associated with health inequality across cultures and how to use this knowledge
      to improve delivery of basic health services.

PMID- 22481146
TI  - Women's empowerment and choice of contraceptive methods in selected African
      countries.
AB  - CONTEXT: It is generally believed that women's lack of decision-making power may
      restrict their use of modern contraceptives. However, few studies have examined
      the different dimensions of women's empowerment and contraceptive use in African
      countries. METHODS: Data came from the latest round of Demographic and Health
      Surveys conducted between 2006 and 2008 in Namibia, Zambia, Ghana and Uganda.
      Responses from married or cohabiting women aged 15-49 were analyzed for six
      dimensions of empowerment and the current use of female-only methods or couple
      methods. Bivariate and multivariate multinomial regressions were used to identify
      associations between the empowerment dimensions and method use. RESULTS: Positive
      associations were found between the overall empowerment score and method use in
      all countries (relative risk ratios, 1.1-1.3). In multivariate analysis,
      household economic decision making was associated with the use of either female
      only or couple methods (1.1 for all), as was agreement on fertility preferences
      (1.3-1.6) and the ability to negotiate sexual activity (1.1-1.2). In Namibia,
      women's negative attitudes toward domestic violence were correlated with the use
      of couple methods (1.1). CONCLUSIONS: Intervention programs aimed at increasing
      contraceptive use may need to involve different approaches, including promoting
      couples' discussion of fertility preferences and family planning, improving
      women's self-efficacy in negotiating sexual activity and increasing their
      economic independence.

PMID- 22481147
TI  - Stability and change in fertility preferences among young women in Malawi.
AB  - CONTEXT: Although studies have demonstrated change in fertility preferences over
      time, there is a lack of definitive knowledge about the level and direction of
      change among individuals, especially young and unmarried women. Furthermore,
      little is known about the factors associated with changes in fertility
      preferences over time. METHOD: The analysis uses the first five waves of data
      from a longitudinal study of a random sample of women aged 15-25 in southern
      Malawi. The data were collected four months apart over an 18-month period,
      between June 2009 and December 2010. Multinomial logit regression models were
      used to calculate relative risk ratios and identify associations between four
      categories of life events-reproductive, relationship, health and economic-and
      shifts in fertility timing preferences. RESULTS: In each four-month period, more
      than half of the women reported changes in the desired timing of their next
      birth, and delays and accelerations in timing desires were common. Several life
      events, including having a child, entering a serious relationship and changes in
      household finances were associated with changes in the level and direction of
      fertility preference. CONCLUSION: Shifts in fertility timing preferences often
      occur in response to changes in life circumstances. Understanding the reasons for
      these shifts may aid family planning providers in meeting women's contraceptive
      needs.

PMID- 22481148
TI  - Spousal separation and interpretation of contraceptive use and unmet need in
      rural Nepal.

PMID- 22481149
TI  - Analysis of the usefulness of biological parameters for the control of activated
      sludge wastewater treatment plants in an interlaboratory study context.
AB  - The quality of the sludge in Wastewater Treatment Plants (WWTPs) depends on the
      suitable colonization of the flocs by microorganisms. Due to the functional
      importance of these biological constituents, several biological or biological
      related parameters have been commonly used for the control of depuration
      efficiency. According to national and international water regulation
      recommendations, interlaboratory studies have a great relevance to determine
      which parameters are more reliable for their extensive application in routine
      control. However, these studies are also very useful to demonstrate consistency
      in results from multiple laboratories and to develop reliable and reproducible
      methodologies which might be necessary for protocol validation and also for
      accreditation issues to meet regulatory environmental requirements. The main
      purpose of this work was to assess the results obtained in consecutive
      interlaboratory assays in order to determine the concordance degree in the
      application of biological parameters by participating laboratories. Following the
      international recommendations about these studies, a common working protocol was
      proposed. Statistical tests indicated that Sludge Index and several routine
      physical-chemical analyses [V30, Mixed Liquor Suspended Solids (MLSS), Mixed
      Liquor Volatile Solids (MLVS) and Sludge Volumetric Index (SVI)] show low
      variability and therefore are suitable tools for laboratory control. Shannon
      Index and Sludge Biotic Index also presented low variability although a more
      precise protocol would be necessary, in particular the methodology to count small
      flagellates. The abundance and identification of protist species showed low
      concordance among laboratories and three factors were responsible for the low
      reliability of data: population density, size and morphological distinguishable
      characters of the specimens.

PMID- 22481150
TI  - Retail clinics and access to primary care.

PMID- 22481151
TI  - Retail clinic visits: are resident paneled patients more likely to make multiple
      visits?
AB  - BACKGROUND AND OBJECTIVES: Primary care resident physicians generally have
      significantly fewer hours in outpatient clinic per week than staff physicians.
      With the transient nature of a primary care resident's practice, do the patients
      of residents utilize the health care system differently? Our hypothesis was that
      patients paneled with a resident physician would be more likely to utilize retail
      clinics with repeat week day visits than those patients paneled with a staff
      primary care physician. METHODS: A retrospective review of 16,318 retail clinic
      visits made in 2009 was studied. Since the patient making a repeat retail clinic
      visit had experience with the services available, they were making an informed
      decision on the type of care desired (their primary care provider or not). The
      patients who made repeat retail clinical visits were divided into groups by age,
      those younger than 18 years and those 18 years and older. RESULTS: Via multiple
      logistic regression, patients under 18 years demonstrated that a patient paneled
      with a resident physician was no more likely to have repeat visits to the retail
      clinic than a staff physician's patient, when controlling for all other
      variables. Similarly, those ages 18 years and older also demonstrated no
      differences in resident or staff paneled patients in utilization of retail
      clinics during the work day. CONCLUSIONS: Multivariate analysis found no
      difference in the utilization of repeat retail clinic visits during 2009 with
      resident paneled patients as compared to staff physician patients.

PMID- 22481152
TI  - Tolerance of uncertainty and fears of making mistakes among fifth-year medical
      students.
AB  - BACKGROUND AND OBJECTIVES: Tolerance of uncertainty is an important skill among
      general practitioners (GPs). Our aim was to study fifth-year medical students'
      feelings related to facing uncertainty and fears of making mistakes in medical
      decisions. Further, we studied the associations of intolerance of uncertainty
      with demographic factors, the students' fears of making mistakes, and their views
      of a GP's work prior to their ultimate course in general practice. METHODS: A
      questionnaire-based survey was carried out among the fifth-year medical students
      prior to their main course in general practice at the University of Helsinki. The
      questionnaire included demographic variables and inquired about their views of
      their own tolerance of uncertainty, fear of making mistakes, and of a GP's work
      overall. RESULTS: During the years 2008--2010, 307/359 medical students (mean age
      25.7 years, 64% females) responded. Of the respondents, 22% felt they had
      difficulty tolerating uncertainty when making medical decisions. Females reported
      that they tolerated uncertainty poorly more often (27%) than did males (11%).
      Those tolerating uncertainty more poorly were more often afraid of making
      mistakes (100% versus 86%). This group more often considered a GP's work too
      difficult and challenging than did others. CONCLUSIONS: Poor self-reported
      tolerance of uncertainty among medical students is associated with considering a
      GP's work too challenging.

PMID- 22481153
TI  - A reappraisal in Sao Paulo, Brazil (2008) of "The Ecology of Medical Care:" The
      "One Per Thousand's Rule".
AB  - BACKGROUND AND OBJECTIVES: Medical ecology is a conceptual framework introduced
      in 1961 to describe the relationship and utilization of health care services by a
      given population. We applied this conception to individuals enrolled in a private
      health maintenance organization (HMO) in Sao Paulo, Brazil, with the aim of
      describing the utilization of primary health care, verifying the frequency of
      various symptoms, and identifying the roles of different health care sources.
      METHODS: This was a cross-sectional telephone survey among a random sample of
      people enrolled in a private HMO. We interviewed a random sample of non-pregnant
      adults over age 18 using 10 questions about symptoms and health care use during
      the month prior to interview. RESULTS: The final sample consisted of 1,065
      participants (mean age 68 years, 68% female). From this sample, 424 (39.8%)
      reported the presence of symptoms, 311 (29.2%) had a medical office consult, 104
      (9.8%) went directly to an emergency medical department, 63 (5.9%) were
      hospitalized, 22 (2.1%) used complementary medicine resources, seven (0.7%) were
      referred to home care, and one (0.1%) was admitted to an academic hospital.
      CONCLUSIONS: The proportion of study participants referred to an academic care
      center was similar to that observed in previous "medical ecology" studies in
      different populations.

PMID- 22481154
TI  - What happens to orders written for older primary care patients?
AB  - BACKGROUND AND OBJECTIVES: Data are limited on order completion errors in primary
      care. The objective of this study was to determine the incidence and nature of
      order completion errors among community-dwelling older adults. METHODS: This
      prospective, cross-sectional exploratory study was conducted at a suburban family
      medicine clinical teaching site. Patients ?70 years old who received ?one order
      at the study enrollment visit were eligible for inclusion. Errors in completion
      of orders for prescriptions, laboratory tests, imaging studies or screening
      procedures, and specialist referrals were assessed. Logistic regression was used
      to identify the independent variables associated with non-system-based errors.
      RESULTS: A total of 322 orders were written for 93 enrolled patients. An order
      error was identified in 59 (18.3%) orders written for 39 (41.9%) patients (mean
      1.5, range 1--4, SD=0.85): 10 were system-based and 49 were non-system-based
      errors. Non-system-based errors included unfilled prescriptions (9.0%),
      uncompleted orders for imaging studies and screening procedures (13.0%), and
      uncompleted specialist referrals (17.4%). All laboratory orders were completed.
      In a logistic regression model, females were four times more likely to experience
      a non-system-based error than males (OR=4.02, 95% CI=1.43, 11.23). CONCLUSIONS:
      Order completion errors were common in this sample of community-dwelling older
      adults, with non-system-based errors for prescriptions, imaging studies or
      screening procedures, and specialist referrals occurring more frequently than
      system-based errors, particularly among females. Providers should not assume that
      patients will complete orders as intended; rather, longitudinal management
      requires regular patient follow-up and review to ensure order completion.

PMID- 22481155
TI  - Ability of an information mastery curriculum to improve residents' skills and
      attitudes.
AB  - BACKGROUND AND OBJECTIVES: Teaching evidence-based medicine is becoming more
      frequent in family medicine residency education, as is the teaching of
      information mastery, which is using techniques to answer clinical questions at
      the point of care and to keep up with changes in medical knowledge. The goal of
      this study was to determine the effect of an integrated curriculum of information
      mastery on residents' evidence-based medicine knowledge and skills as well as
      their confidence at critically appraising medical literature and using evidence
      to inform clinical decisions. METHODS: We used a before-after study in a single
      residency over 5 years. Residents completed the Fresno Test of Evidence-based
      Medicine and an attitude questionnaire at the start of the curriculum and then
      again before graduation. The integrated curriculum consisted of intensive
      instruction over the course of 1 month (30 hours), followed by a longitudinal
      series of ongoing conferences, integrated into the teaching of clinical content.
      Teaching was also integrated into day-to-day clinical activities via precepting
      interactions. RESULTS: Twenty-three residents completed the study. Modified
      Fresno Test scores significantly improved from 104.0 to 121.5. Using a pass/fail
      approach, nine residents (40.1%) passed the test at the start of training,
      increasing to 17 (73.4%) at the end of the intervention. Confidence in critical
      appraisal scores increased from an average 17.90 (95% CI=16.55--19.25) to 21.10
      (95% CI=19.49--22.71), out of a possible score of 25. Confidence scores were
      significantly lower in residents who did not pass the posttest (18.5 versus
      21.9). Attitudes regarding confidence in the use of evidence and a decreased
      reliance on experts were also improved following the curriculum. CONCLUSIONS: A
      curriculum of information mastery, integrated across the greater curriculum,
      improved trainees' evidence-based medicine knowledge and skills and attitude
      toward using evidence to inform clinical decision making.

PMID- 22481156
TI  - Facilitating resident well-being: a pilot intervention to address stress and
      teamwork issues on an inpatient service.
AB  - BACKGROUND AND OBJECTIVES: Residency presents unique challenges for learners with
      regard to stress management and working with others to deliver quality patient
      care. To address resident concerns about stress and teamwork on a family medicine
      inpatient service, a structured 15-minute intervention was implemented weekly,
      over a 20-month period. The intervention was conducted by the clinical
      psychologist and inpatient service medical director. Residents rated their
      respective stress levels at each session, and facilitators engaged them in
      problem solving if their stress level was rated 7 or higher on a 0--10 scale.
      Twenty-six residents experienced the intervention on multiple occasions. The
      amount of resident participation in the intervention varied based on the
      resident's level of training during the intervention period. METHODS: Residents
      (n=26) completed a brief questionnaire regarding the effectiveness of the
      intervention at the end of each 4-week block in which they participated. One
      hundred of a possible 108 questionnaires were completed (92%). RESULTS:
      Questionnaire items were rated on a 7-point Likert scale ranging from 1 (not at
      all effective) to 7 (very effective). Resident-rated helpfulness of the
      intervention ranged from a mean of 5.28 (SD=1.30, Resolving Communication
      Difficulties) to 5.76 (SD=1.06, Facilitating Discussion of Stressful Aspects of
      Work). Most resident-identified stressors were resolved during the scheduled
      meetings; only five additional meetings were needed during the 20 months of the
      project to achieve resolution of resident stressors. CONCLUSIONS: The
      intervention is time- and cost-efficient, addresses at least two of the
      Accreditation Council on Graduate Medical Education (ACGME) competencies
      (professionalism and interpersonal and communication skills) as well as Agency
      for Healthcare Research and Quality teamwork competencies (leadership,
      communication, situation monitoring, and mutual support) and can easily be
      adapted by other specialties.

PMID- 22481157
TI  - The talk.

PMID- 22481158
TI  - The good, the bad, and the ugly.

PMID- 22481159
TI  - Keep at it.

PMID- 22481160
TI  - Balancing equivalence and equipoise in medical education research.

PMID- 22481161
TI  - Five-year survival.

PMID- 22481162
TI  - The Arabidopsis ubiquitin ligases ATL31 and ATL6 control the defense response as
      well as the carbon/nitrogen response.
AB  - In higher plants, the metabolism of carbon (C) and nitrogen nutrients (N) is
      mutually regulated and referred to as the C and N balance (C/N). Plants are thus
      able to optimize their growth depending on their cellular C/N status. Arabidopsis
      ATL31 and ATL6 encode a RING-type ubiquitin ligases which play a critical role in
      the C/N status response (Sato et al. in Plant J 60:852-864, 2009). Since many ATL
      members are involved in the plant defense response, the present study evaluated
      whether the C/N response regulators ATL31 and ATL6 are involved in defense
      responses. Our results confirmed that ATL31 and ATL6 expression is up-regulated
      with the microbe-associated molecular patterns elicitors flg22 and chitin as well
      as with infections with Pseudomonas syringae pv. tomato DC3000 (Pst. DC3000).
      Moreover, transgenic plants overexpressing ATL31 and ATL6 displayed increased
      resistance to Pst. DC3000. In accordance with these data, loss of ATL31 and ATL6
      function in an atl31 atl6 double knockout mutant resulted in reduced resistance
      to Pst. DC3000. In addition, the molecular cross-talk between C/N and the defense
      response was investigated by mining public databases. The analysis identified the
      transcription factors MYB51 and WRKY33, which are involved in the defense
      response, and their transcripts levels correlate closely with ATL31 and ATL6.
      Further study demonstrated that the expression of ATL31, ATL6 and defense marker
      genes including MYB51 and WRKY33 were regulated by C/N conditions. Taken
      together, these results indicate that ATL31 and ATL6 function as key components
      of both C/N regulation and the defense response in Arabidopsis.

PMID- 22481164
TI  - Angiotensin II-mediated left ventricular abnormalities in chronic kidney disease.
AB  - Angiotensin II (ATII), the biologically active product of the renin-angiotensin
      system (RAS), is involved in modulation of left ventricular (LV) structure and
      function in chronic kidney disease (CKD). Because the RAS system is overactive in
      CKD, excess ATII accumulates in the heart, thereby promoting myocyte hypertrophy,
      fibroblast proliferation, interstitial accumulation of collagen, and microvessel
      disease. These cardiac abnormalities are further enhanced by a possible
      interaction between enhanced RAS activity and hypercalcemia, hyperphosphatemia
      and secondary hyperparathyroidism, and vitamin D deficiency. The ATII-associated
      stimulation of aldosterone production from the adrenal gland and the increase in
      activity of the sympathetic system in CKD, further contribute to LV
      abnormalities. Myocardial structural changes are major determinants of an
      increase in myocardial stiffness, leading to LV diastolic and systolic function
      impairment, and clinical congestive heart failure. Other complications include
      cardiac conduction disturbances, QT prolongation, and arrhythmias, which all
      contribute to elevated cardiovascular mortality in patients with CKD.

PMID- 22481163
TI  - Physical mapping of a pollen modifier locus controlling self-incompatibility in
      apricot and synteny analysis within the Rosaceae.
AB  - S-locus products (S-RNase and F-box proteins) are essential for the gametophytic
      self-incompatibility (GSI) specific recognition in Prunus. However, accumulated
      genetic evidence suggests that other S-locus unlinked factors are also required
      for GSI. For instance, GSI breakdown was associated with a pollen-part mutation
      unlinked to the S-locus in the apricot (Prunus armeniaca L.) cv. 'Canino'. Fine
      mapping of this mutated modifier gene (M-locus) and the synteny analysis of the M
      locus within the Rosaceae are here reported. A segregation distortion loci
      mapping strategy, based on a selectively genotyped population, was used to map
      the M-locus. In addition, a bacterial artificial chromosome (BAC) contig was
      constructed for this region using overlapping oligonucleotides probes, and BAC
      end sequences (BES) were blasted against Rosaceae genomes to perform micro
      synteny analysis. The M-locus was mapped to the distal part of chr.3 flanked by
      two SSR markers within an interval of 1.8 cM corresponding to ~364 Kb in the
      peach (Prunus persica L. Batsch) genome. In the integrated genetic-physical map
      of this region, BES were mapped against the peach scaffold_3 and BACs were
      anchored to the apricot map. Micro-syntenic blocks were detected in apple (Malus
      * domestica Borkh.) LG17/9 and strawberry (Fragaria vesca L.) FG6 chromosomes.
      The M-locus fine-scale mapping provides a solid basis for self-compatibility
      marker-assisted selection and for positional cloning of the underlying gene, a
      necessary goal to elucidate the pollen rejection mechanism in Prunus. In a wider
      context, the syntenic regions identified in peach, apple and strawberry might be
      useful to interpret GSI evolution in Rosaceae.

PMID- 22481165
TI  - Identification of two novel mutations in TRPS1 gene in families with tricho-rhino
      phalangeal type I syndrome.
AB  - BACKGROUND: Autosomal dominant tricho-rhino-phalangeal syndrome I (TRPS I) is due
      to mutations in the TRPS1 gene. Tricho-rhino-phalangeal syndrome I is
      characterized by peculiar face and skeletal anomalies. Cone-shaped epiphyses are
      the characteristic radiographic findings. OBJECTIVE: To describe 2 families with
      TRPS I and 2 novel mutations in the TRPS1 gene. PATIENTS: The study included 2
      nonrelated families with TRPS I. All exons of the TRPS1 gene were analyzed from
      genomic DNA. RESULTS: The TRPS1 gene mutation analysis showed in family 1 the
      c.978C>A nonsense mutation within exon 4 and in family 2 the c.164A>C missense
      mutation within exon 3. CONCLUSIONS: We found 2 families with TRPS1 caused by 2
      novel mutations in the TRPS gene, particularly a missense mutation in exon 3,
      outside the GATA zinc finger domain, that leads a mild TRPS phenotype. Our data
      show a higher genotypic spectrum in the TRPS I and demonstrate that mutations in
      the amino terminus of the transcription factor result in TRPS I syndrome.

PMID- 22481166
TI  - Vitamin D deficiency is associated with the development of subclinical coronary
      artery disease in African Americans with HIV infection: a preliminary study.
AB  - BACKGROUND: Premature coronary artery disease (CAD) is a major concern in human
      immunodeficiency virus (HIV)-infected African Americans. The objectives of the
      study were to estimate the incidence of subclinical CAD, defined by the presence
      of coronary plaque and/or calcification on cardiac computed tomography (CT), and
      to identify the associated risk factors in this vulnerable population. SUBJECTS
      AND METHODS: Between August 2003 and September 2010, 188 HIV-infected African
      Americans without known, or symptoms of, CAD underwent cardiac CT. The subset
      without demonstrable disease underwent a second cardiac CT approximately 2 years
      later. The incidence of disease over that period and the effects of
      antiretroviral treatment and other known and hypothesized risk factors were
      investigated. RESULTS: Sixty-nine of these 188 African Americans had evidence of
      subclinical disease on the initial cardiac CT, confirming prior high prevalence
      reports. A second cardiac CT was performed on 119 African Americans without
      disease approximately 2 years later. The total person-years of follow-up was
      284.4. Subclinical CAD was detected in 14 of these, yielding an overall incidence
      of 4.92/100 person-years (95% confidence interval, 2.69-8.26). Among the factors
      investigated, only male sex and vitamin D deficiency were independently
      associated with the development of subclinical CAD. The study did not find
      significant associations between CD4 count, HIV viral load, antiretroviral
      treatment use, or cocaine use and the incidence of subclinical CAD. CONCLUSIONS:
      The incidence of subclinical CAD in African Americans with HIV infection is
      provocatively high. Larger studies are warranted to confirm the role of vitamin D
      deficiency in the development of CAD in HIV-infected African Americans.

PMID- 22481167
TI  - Serum cytokines and cancer in involuntary weight loss.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL
      1beta), and IL-6 may be associated with involuntary weight loss in patients with
      and without cancer. However, results of previous studies have been conflicting.
      We evaluated patients who had involuntary weight loss to determine cytokine
      levels and the correlation of these cytokines with weight loss, the association
      with inflammation, and the potential for use in cancer diagnosis. MATERIALS AND
      METHODS: In 290 consecutive patients with involuntary weight loss (74 patients
      [26%] with cancer and 216 patients [74%] without cancer), erythrocyte
      sedimentation rate (ESR), and serum levels of C-reactive protein, TNF-alpha, IL
      1beta, and IL-6 were determined. RESULTS: Higher ESR and levels of C-reactive
      protein, TNF-alpha, IL-1beta, and IL-6 were associated with cancer. The levels of
      TNF-alpha, IL-1beta, and IL-6 did not correlate with the amount of weight loss.
      In multivariable analysis, only ESR was associated with cancer. CONCLUSIONS: In
      patients with involuntary weight loss, TNF-alpha, IL-1beta, and IL-6 were
      associated with cancer but were not weight loss mediators.

PMID- 22481168
TI  - First-principles calculations of helium and neon desorption from cavities in
      silicon.
AB  - Combining density functional theory, the nudged elastic band technique, and the
      ultradense fluid model, we investigated the desorption process of He and Ne in
      silicon. Our results show that the internal surfaces of gas-filled bubbles are
      not a limiting factor during desorption experiments, since the surface
      reconstruction opens diffusion paths easier than in the bulk. We show that the
      vibrational contribution to the energy of helium in the bulk has to be considered
      in order to determine realistic pressures in the bubbles, when comparing
      experiments and simulations. At the maximum of desorption, an average pressure of
      1-2 GPa is computed.

PMID- 22481169
TI  - Sulfur dioxide adsorption and photooxidation on isotopically-labeled titanium
      dioxide nanoparticle surfaces: roles of surface hydroxyl groups and adsorbed
      water in the formation and stability of adsorbed sulfite and sulfate.
AB  - Transmission FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS) are
      used to probe the details of sulfur dioxide adsorption and photooxidation on
      titanium dioxide nanoparticle surfaces. Adsorption sites, surface speciation and
      photooxidation chemistry have been determined from analysis of FTIR spectra in
      conjunction with isotope labeling experiments. These data show that surface
      hydroxyl groups are involved in the adsorption of sulfur dioxide, and in
      particularly, sulfur dioxide reacts with either one surface O-H group to yield
      adsorbed bisulfite or two surface O-H groups to yield adsorbed sulfite and water.
      Using (16)O-H, (16)O-D and (18)O-H labeled surface O-H groups, additional
      insights into the adsorption mechanism as well as shifts in the vibrational modes
      of adsorbed sulfite have been determined. Upon irradiation, adsorbed
      sulfite/bisulfite converts to adsorbed sulfate. The relative stability of
      adsorbed sulfite to adsorbed sulfate on TiO2 nanoparticle surfaces was also
      examined in the presence of increasing relative humidity (RH). It is shown here
      that adsorbed water can more easily displace sulfite compared to sulfate by
      forming a stable sulfur dioxide water complex in the presence of adsorbed water.
      These differences in the RH-dependent stability of adsorbed species that form as
      a result of surface heterogeneous reactions on oxide particles surfaces has
      important implications in the heterogeneous chemistry of mineral dust aerosol in
      the atmosphere. 

PMID- 22481170
TI  - Large array of single, site-controlled InAs quantum dots fabricated by UV
      nanoimprint lithography and molecular beam epitaxy.
AB  - We present the growth of single, site-controlled InAs quantum dots on GaAs
      templates using UV-nanoimprint lithography and molecular beam epitaxy. A large
      quantum dot array with a period of 1.5 um was achieved. Single quantum dots were
      studied by steady-state and time-resolved micro-photoluminescence experiments. We
      obtained single exciton emission with a linewidth of 45 ueV. In time-resolved
      experiments, we observed decay times of about 670 ps. Our results underline the
      potential of nanoimprint lithography and molecular beam epitaxy to create large
      scale, single quantum dot arrays.

PMID- 22481171
TI  - Sensitive measurement of optical nonlinearity in amorphous chalcogenide materials
      in nanosecond regime.
AB  - The present work focuses on the nonlinear optical behavior of chalcogenide
      As(2)S(3) film as well as on bulk material. The thin film of As(2)S(3) grown by
      thermal evaporation and bulk glass developed by melt-quenched technique has been
      characterized using nanosecond pulses of Nd:YAG (532 nm) and Nd:YVO(4) (1,064 nm)
      laser. Using Z-scan technique, the laser induced nonlinear optical parameters
      viz. nonlinear refractive index (n(2)), nonlinear absorption coefficient (beta)
      and third order nonlinear susceptibility (chi(3)) have been estimated. At 1,064
      nm excitation, the materials exhibit stronger nonlinearity as compared to that of
      532 nm laser. In case of As(2)S(3) thin film, observed nonlinearity attributes to
      two-photon absorption. The optical limiting response of chalcogenide film as well
      as bulk sample has also been reported. The study predicts that the As(2)S(3) thin
      film is a better optical limiting material than bulk glass due to relatively
      higher nonlinearity and lower limiting threshold.

PMID- 22481172
TI  - Combustion synthesis, structural characterization, thermo and photoluminescence
      studies of CdSiO3:Dy3+ nanophosphor.
AB  - CdSiO(3):Dy(3+) (1-9mol%) nanophosphors were prepared for the first time using
      the solution combustion method. The process of monoclinic phase formation was
      investigated by PXRD, TG-DTA and FTIR. The results show that the phase formation
      temperature of combustion-derived monoclinic CdSiO(3) is found to be lower as
      compared to the powders prepared by solid-state and sol-gel methods. It was
      observed that the average crystallite size calculated by Debye-Scherrer's formula
      and Williamson-Hall (W-H) plot are well comparable and was found to be in the
      range of 35-70 nm. Scanning electron micrographs indicate that there exist
      circular microcrystalline particles. It is observed that the optical energy gap
      is widened with the increase of Dy(3+) ion dopant. The photoluminescence (PL)
      spectra exhibit characteristic transitions of Dy(3+) due to (4)F(9/2)->(6)H(15/2)
      (blue) and (4)F(9/2)->(6)H(13/2) (yellow) regions. The thermoluminescence (TL)
      glow curve of CdSiO(3):Dy(3+) nano powder exposed to UV irradiation exhibited one
      main peak centered at 170 degrees C. The intensity of the main peak increases up
      to the dose of 20 min then it decreases. The glow curves were analyzed by the
      glow peak shape method and the estimated trap parameters are discussed.

PMID- 22481173
TI  - Vibronic and cation spectroscopy of 2,4-difluoroaniline.
AB  - We applied the two-color resonant two-photon ionization and mass-analyzed
      threshold ionization techniques to record the vibronic and cation spectra of 2,4
      difluoroaniline. The cation spectra were recorded by ionizing via the 0(0), X(1),
      6b(1), and 1(1) levels of the electronically excited S(1) state. Most of the
      observed active modes of this molecule in the S(1) and cationic ground D(0)
      states are related to the in-plane ring deformation vibrations. The band origin
      of the S(1)<-S(0) electronic excitation was found to appear at 33294 +/- 2 cm(
      1), whereas the adiabatic ionization energy was determined to be 63935 +/- 5 cm(
      1). Comparing the data of 2,4-difluoroaniline with those of aniline, 2
      fluoroaniline, and 4-fluoroaniline, one can learn the effects of fluorine
      substitution on the electronic transition and molecular vibration.

PMID- 22481174
TI  - Binding interaction of 1-(4-methybenzyl)-2-p-tolyl-1H-benzo[d]imidazole with
      bovine serum albumin.
AB  - A promising benzimidazole derivative 1-(4-methybenzyl)-2-p-tolyl-1H
      benzo[d]imidazole (MBTBI) has been synthesized and characterized by single
      crystal XRD, NMR, mass and IR spectral techniques. The mutual interaction of this
      benzimidazole derivative (MBTBI) with bovine serum albumin (BSA) was investigated
      using solution spectral studies. The fluorescence quenching mechanism of BSA by
      MBTBI was analyzed and the binding constant has been calculated. The binding
      distance between these two was obtained based on the theory of Forester's non
      radiation energy transfer (FRET). The effect of some common ions on the binding
      constant was also examined.

PMID- 22481175
TI  - Spectroscopic and spectrofluorimetric studies on the interaction of albendazole
      and trimethoprim with iodine.
AB  - Raman, UV-vis, FT-IR, and fluorescence spectral techniques were employed to
      investigate the mechanism of interaction of albendazole (ALB) and trimethoprim
      (TMP) drugs with iodine. Interactions of ALB and TMP with iodine yields triiodide
      ion and its formation was confirmed by electronic and Raman spectra. The peaks
      appeared in Raman spectra of the isolated products are at around 145, 113 and 82
      cm(-1) are assigned to nu(as)(I-I), nu(s)(I-I) and delta(I(3)(-)) respectively,
      confirmed the presence of I(3)(-) ion. Formation constant (K), molar extinction
      coefficient (E) and thermodynamic properties DeltaH(#), DeltaS(#) and DeltaG(#)
      were determined and discussed. Fluorescence quenching studies indicated that the
      interaction between the ALB, TMP with iodine are spontaneous and the TMP-iodine
      interaction is found to be stronger than that the other system. Solvent variation
      studies indicated that the binding constant increased with an increase in
      polarity of the medium.

PMID- 22481176
TI  - Effect of gamma radiation on low density polyethylene (LDPE) films: optical,
      dielectric and FTIR studies.
AB  - The low density polyethylene (LDPE) films were irradiated with gamma radiation in
      the dose range varied from 20 to 400 kGy. The induced changes in the chemical
      structure and dielectric properties for the irradiated films were investigated.
      The structure modifications: crystallinity as well as possible molecular changes
      of the polymer were recognized using Fourier Transform Infrared Spectroscopy
      (FTIR). The optical results were determined from transmission, reflection and
      absorption spectra for these films. The dielectric properties of these films were
      calculated using optical methods. Result indicates small variation in
      crystallinity which could be increased or decreased depending on the relative
      importance of the structural and chemical changes.

PMID- 22481177
TI  - Experimental and quantum chemical computational study of (E)-1-[5-(3,4
      dimethylphenyldiazenyl)-2-hydroxyphenyl]ethanone.
AB  - In this work, the azo dye, (E)-1-[5-(3,4-dimethylphenyldiazenyl)-2
      hydroxyphenyl]ethanone, has been synthesized and characterized by IR, and X-ray
      single-crystal determination. In the theoretical calculations, the stable
      structure geometry of the isolated molecule in gas phase was investigated under
      the framework of the density functional theory (B3LYP) with 6-31G (d, p). To
      designate lowest energy molecular conformation of the title molecule, the
      selected torsion angle was varied every 10 degrees  and the molecular energy
      profile was calculated from -180 degrees  to +180 degrees . Besides, molecular
      electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis, and
      thermodynamic properties were described from the computational process. In
      addition to these calculations, we were investigated solvent effects on the
      nonlinear optical properties (NLO) of the title compound.

PMID- 22481178
TI  - Vibrational spectroscopic investigation on the structure of 2-ethylpyridine-4
      carbothioamide.
AB  - Fourier transform Raman and Fourier transform infrared spectra of 2-ethylpyridine
      4-carbothioamide were recorded in the regions 3600-100 cm(-1) and 4000-450 cm(
      1), respectively in the solid phase. 2-Ethylpyridine-4-carbothioamide is used as
      anti-tubercular agent that inhibits mycolic acid synthesis. The equilibrium
      geometry harmonic vibrational frequencies, infrared intensities and Raman
      scattering activities were calculated by Hartee Fock and density functional B3LYP
      methods with 6-31 G (d,p) basis set, using Gaussian 03 W program package on a
      Pentium IV/1.6 GHz personal computer(.) A detailed interpretation of the
      vibrational spectra of this compound has been made on the basis of the calculated
      potential energy distribution (PED). The thermodynamic functions of the title
      compound were also performed at the above methods and basis set. A detailed
      interpretation of the infrared and Raman spectra of 2-ethylpyridine-4
      carbothioamide is reported. The (1)H and (13)C nuclear magnetic resonance (NMR)
      chemical shifts of the molecules were calculated using the GIAO method confirms
      with the experimental values. Stability of the molecule arising from hyper
      conjugative interactions, charge delocalization has been analyzed using natural
      bond orbital (NBO) analysis. The linear polarizability (alpha) and the first
      order hyperpolarizability (beta) values of the investigated molecule have been
      computed using DFT quantum mechanical calculations. The HOMO and LUMO energy gap
      reveals that the energy gap reflects the chemical activity of the molecule. The
      observed and calculated wave numbers are found to be in good agreement. The
      experimental spectra also coincide satisfactorily with those of theoretically
      constructed spectra.

PMID- 22481180
TI  - Arsenic fractionation in mine spoils 10 years after aided phytostabilization.
AB  - Aided phytostabilization using a combination of compost, zerovalent iron grit and
      coal fly ash (CZA) amendments and revegetation effectively promoted the
      biological recovery of mining spoils generated at a gold mine in Portugal.
      Selective dissolution of spoil samples in combination with solid phase
      characterization using microbeam X-ray absorption near edge structure (MUXANES)
      spectroscopy and microbeam X-ray fluorescence (MUXRF) mapping were used to assess
      As associations in spoils ten years after CZA treatment. The results show that As
      preferentially associates with poorly crystalline Fe-oxyhydroxides as opposed to
      crystalline Fe-(oxyhydr)oxide phases. The crystalline Fe(III)-phases dominated in
      the treated spoil and exceeded those of the untreated spoil three-fold, but only
      2.6-6.8% of total As was associated with this fraction. Correlation maps of As:Fe
      reveal that As in the CZA-treated spoils is primarily contained in surface
      coatings as precipitates and sorbates. Arsenic binding with poorly crystalline Fe
      oxyhydroxides did not inhibit As uptake by plants.

PMID- 22481179
TI  - Interactions of 14C-labeled multi-walled carbon nanotubes with soil minerals in
      water.
AB  - Carbon nanotubes are often modified to be stable in the aqueous phase by adding
      extensive hydrophilic surface functional groups. The stability of such CNTs in
      water with soil or sediment is one critical factor controlling their
      environmental fate. We conducted a series of experiments to quantitatively assess
      the association between water dispersed multi-walled carbon nanotubes (MWCNTs)
      and three soil minerals (kaolinite, smectite, or shale) in aqueous solution under
      different sodium concentrations. (14)C-labeling was used in these experiments to
      unambiguously quantify MWCNTs. The results showed that increasing ionic strength
      strongly promoted the removal of MWCNTs from aqueous phase. The removal tendency
      is inversely correlated with the soil minerals' surface potential and directly
      correlated with their hydrophobicity. This removal can be interpreted by the
      extended Derjaguin-Landau-Verwey-Overbeek (EDLVO) theory especially for kaolinite
      and smectite. Shale, which contains large and insoluble organic materials, sorbed
      MWCNTs the most strongly.

PMID- 22481181
TI  - Model description of trophodynamic behavior of methylmercury in a marine aquatic
      system.
AB  - A marine food web in Bohai Bay, China, was selected to study methylmercury (MeHg)
      bioaccumulation, and an aquivalence-based mass balance model was established to
      explore the possibility of predicting the MeHg concentrations and quantifying
      MeHg bioaccumulation in the food web. Results showed that both total mercury
      (THg) and MeHg were biomagnified in the food web. The calculated MeHg
      concentrations in the selected species agreed well with the measured values,
      which shows the model could be a useful tool in MeHg concentration prediction in
      food web. Model outputs also showed that metabolism and growth dilution could be
      the dominant mechanisms for the reduction of MeHg levels in aquatic organisms.
      With the increase of trophic level, the contribution of food as a MeHg source for
      organism is increasing, and MeHg from prey was the dominant source.

PMID- 22481182
TI  - The past, present, and future of the debate over return of research results and
      incidental findings.

PMID- 22481183
TI  - Return of results: not that complicated?

PMID- 22481185
TI  - Carrier dynamics in type-II GaAsSb/GaAs quantum wells.
AB  - Time-resolved photoluminescence (PL) characteristics of type-II GaAsSb/GaAs
      quantum wells are presented. The PL kinetics are determined by the dynamic band
      bending effect and the distribution of localized centers below the quantum well
      band gap. The dynamic band bending results from the spatially separated electron
      and hole distribution functions evolving in time. It strongly depends on the
      optical pump power density and causes temporal renormalization of the quantum
      well ground-state energy occurring a few nanoseconds after the optical pulse
      excitation. Moreover, it alters the optical transition oscillator strength. The
      measured PL lifetime is 4.5 ns. We point out the critical role of the charge
      transfer processes between the quantum well and localized centers, which
      accelerate the quantum well photoluminescence decay at low temperature. However,
      at elevated temperatures the thermally activated back transfer process slows down
      the quantum well photoluminescence kinetics. A three-level rate equation model is
      proposed to explain these observations.

PMID- 22481186
TI  - [Multi slice computerized tomography of the heart and coronary arteries].
AB  - BACKGROUND: Due to the recent technological progress, multislice computerized
      tomography (MSCT) allows visualizing the heart and coronary arteries. Multislice
      computed tomography is non invasive and provides high quality images.Its main
      limits are arythmia, tachycardia and coronary calcifications. But the main
      drawback with MSCT is the radiation dose. AIM: Report of usefuluess and
      indications of multislice CT scanner. METHODS: Rzview of literature RESULTS:
      Although the indications of MSCT did not reach a guideleness level yet, some
      trends can be stated. The advantages and limitations of MSCT in cardiac
      exploration are summarized in this article. The indications are mainly based on
      the excellent negative predictive value of MSCT regarding coronary artery
      disease. Hence, patients at low to moderate risk of coronary artery disease
      mostly benefit of the technique. MSCT can be an alternate examination in case of
      non feasible or non contributive ischemic test. MSCT is highly contributive in
      the ostial analysis, in detecting abnormal congenital coronary anomalies or in
      analysing bypass grafts. MSCT remains limited in patients with heavily calcified
      coronary arteries, and in patients with stented distal arteries. CONCLUSION:
      Multislice CT scanner should not be considered as equivalent to invasive coronary
      angiography bu it is a additional diagnostic tool.

PMID- 22481187
TI  - [Riedel's thyroiditis].

PMID- 22481188
TI  - Transient complete loss of vision after transurethral resection of the prostate.

PMID- 22481189
TI  - [Primary intestinal T lymphoma].

PMID- 22481190
TI  - [Blunt left diaphragmatic rupture].

PMID- 22481191
TI  - [Post-infectious irritable bowel syndrome].
AB  - BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) is a disorder
      wherein symptoms of IBS begin after an episode of acute gastroenteritis. AIMS: To
      determine epidemiology, clinical features and prognosis of PI-IBS and to precise
      its physiopathology and treatment. METHODS: Literature review. RESULTS: Published
      studies have reported an incidence of PI-IBS ranging from 4 to 32 % with a mean
      of 10 %. Bacterial infections are the most responsible agents. Risk factors for
      PI-IBS include patient's demographics, psychological disorders and the severity
      of enteric illness. The most common symptoms are those of diarrheapredominant
      IBS. The mechanisms underlying PI-IBS include especially changes in intestinal
      permeability and persistent mucosal inflammatory process. In fact, there is
      increase in lymphocytic, mast and enterochromaffin cells in the gut mucosa.
      Furthermore, increased inflammatory cytokines have been demonstrated. Treatment
      of PIIBS is similar to that idiopathic IBS. CONCLUSION: PI-IBS is a novel clinic
      entity that suggests a novel approaches to IBS.

PMID- 22481192
TI  - [Offensive and criminal acts in schizophrenia: comparative study according to
      gender].
AB  - BACKGROUND: Schizophrenia does not involve the same risk of violence among women
      than men. The offensive and criminal acts were less studied in women. AIMS: To
      raise the sex ratio of the criminal acts and to seek the characteristics and the
      risk factors of this female violence. METHODS: We carried out a comparative
      descriptive retrospective study, including 107 patients having schizophrenia
      according to criteria's of the DSM IV, hospitalized due to insanity according to
      article 38 of the Tunisian Penal Code. RESULTS: The sex ratio was 1 woman for 10
      men. The women were older at the time of the offence or criminal act (46 years,
      39 years), men were more often unmarried or divorced (50% vs 89.7%) and had more
      psychiatric family history (30% vs 40,2%). The duration of untreated psychoses
      was longer among women (65.3 months vs 22.4 months). The women more often made
      homicides or attempts of homicides (70%, 33%), the infanticides were raised only
      among women and arsons were noted only among men. The hospitalization was
      significantly longer among women (18.8 monthsvs 11.2 months). CONCLUSION: The
      preventive of offence and criminal acts in schizophrenia is also necessary among
      women as men.

PMID- 22481193
TI  - [Procedural pain assessment after spinal injections of corticosteroid].
AB  - BACKGROUND: Spinal injections of corticosteroid are commonly performed by
      rheumatologists in their daily practice but little is known about the frequency,
      the intensity and the management of procedural pain observed in these
      osteoarticular injections in daily practice. AIM: To evaluate the prevalence and
      intensity of pain caused by spinal injections. METHODS: In this observational
      prospective study, data were collected over 6 months, for up to 44 procedures
      (corticosteroid spinal injection). Evaluation of the pain was evaluated
      immediately before and after the injection using Huskisson's visual analogue
      scale (VAS). Statistical analysis was carried out in order to compare patients
      who had suffered from pain whilst undergoing the procedure to those who had not.
      RESULTS: Data were analyzed for 17 patients (12 female, mean age 53.6 +/- 10.5
      years). Over 50% of patients experienced procedural pain. Significant predictive
      factors of genesis of the procedural pain were the young age (p=0.022) and the
      intensity of the initial pain (p < 0.001), while the existence of a co morbidity
      is rather a protective factor (p = 0.006). Others factors such us sex, origin,
      level of studies, socioeconomic conditions, didn't seem to have of effect on the
      procedural pain. CONCLUSION: Most patients undergoing spinal injections suffer
      from procedural pain. Specific research and guidelines for the management of
      procedural pain related to rheumatologic care should be established to improve
      the quality of care provided by physicians.

PMID- 22481194
TI  - [Neuroradiological pattern of peripartum cerebro vascular disease medicating
      transfer to determine care unit].
AB  - BACKGROUND: Pregnancy and puerperium are considered a period of a high risk of
      stroke responsible in a part of the morbidity and mortality in women. Imaging is
      the pivotal tool to diagnostics and care. AIM: To investigate the clinical and
      imaging features cerebrovascular complications during pregnancy and in post
      partum period. METHODS: We report a retrospective analysis of forty four patients
      (November 2002 - October 2010) admitted in the intensive car department of the
      national institute of neurology for cerebro-vascular complications during
      pregnancy and in post partum period. RESULTS: Cerebro-vascular imaging modalities
      included cerebral computed tomography (CCT) with and without contrast in 94% of
      cases, magnetic resonance imaging (MRI) in 30.6% of cases completed by venous
      angiography MRI in 27.2% of cases and angiography MRI of Willis polygon in 11.3%
      of cases and by cerebral angiography in 13.6% of cases. Posterior reversible
      encephalopathy syndrome (PRES) is diagnosed in 61.4 % of cases followed by
      meningo-cerebral haemorrhage (MCH) in 29.5% and finally cerebral venous
      thrombosis (CVT) and arterial ischemia in 4.5% of cases each one. The cerebro
      vascular complications are revelled in 86.3 % of the cases during the postpartum
      and were associated with the eclampsia or preeclampsia in 90.9 % of the cases
      (n=40). CCT showed typical lesions of PRES in 23 patients. It confirms the
      presence of hematoma in the 13 patients with MCH and find hypodense lesion in one
      case with ischemic stroke. CCT show direct (delta sign) and indirect signs of
      CVT. MRI confirms the diagnostic of PRES, when done (11 of 12 cases) and show
      cortical sub cortical hyper signal on T2 and FLAIR and hypo signal on T1
      sequences. MRI was normal in one case. It shows hemorrhagic lesion in the 2 cases
      of MCH, thrombosis in the cases of CVT and ischemic lesion in the cases of
      ischemic stroke. CCT and MRI done within 48 hours from admission were decisive
      for early diagnostic and for fast and adequate care. CONCLUSION: Early
      recognition of stroke in peri partum by cerebral imaging is of paramount
      importance for prompt diagnosis and treatment to improve maternal morbidity and
      mortality.

PMID- 22481195
TI  - Selective salpingography and tubal catheterization in infertile women.
AB  - BACKGROUND: Use of selective salpingography (SS) and fallopian tube
      catheterization (TC) has revolutionized the diagnosis and treatment of proximal
      tubal infertility. AIM: To evaluate results of women treated for proximal tubal
      obstruction by selective salpingography and tubal catherization. METHODS:
      Selective salpingography was performed in women with proximal bilateral tubal
      obstructions. Follow-up ranged from 4 to 12 months. RESULTS: twelve patients had
      been shown to have bilateral proximal obstruction of the fallopian tube. After
      SS/TC, patency was achieved in 8 cases. Spontaneous conceptions occurred in 4
      women. CONCLUSION: SS and TC should be used more widely because it is simple and
      effective in case of proximal tubal blockage.

PMID- 22481196
TI  - [What is has the artificial sweeteners in indication the food of our diabetics?].
AB  - BACKGROUND: Artificial Sweeteners are food additives increasingly developed by
      the food industry. AIM: Study of the consumption of sweeteners in diabetic
      patients. METHODS: This prospective cross study performed using a questionnaire
      to 100 patients recruited at random outpatients of the National Institute of
      Nutrition. Data on the BMI,the blood sugar were found in clinical records.
      RESULTS: 94% of diabetics have at least heard of sweeteners and 50% use it
      regularly. Sweetener table are the most consumed sweeteners, in order of
      frequency Saccharin, Sucralose and Aspartame, used to sweeten coffee and tea. The
      trade products "light" are consumed by 29% of patients. Yet consumers have no
      real information on these products. There was no statistically significant
      correlation between the consumption of sweeteners and BMI, balance and diabetes
      evolution. A statistically significant correlation was found between consumption
      and socio-economic and cultural development of patients. CONCLUSION: The
      education of diabetic patients should include information of patients on these
      sweeteners, their interest, their against-indications and adverse reactions.

PMID- 22481197
TI  - [Clinical and phmetric evaluation of gastro-esophageal reflux impact on upper
      airways in adult].
AB  - BACKGROUND: Gastroesophageal reflux is a frequent and benign affection. It
      represents an etiopathological entity in otorhinolaryngology; that may occasion a
      large variety of ENT manifestations. AIM: To evaluate clinical and pHmetric
      impact of gastro esophageal reflux on upper airways in adult. METHODS:
      Prospective study about 95 cases diagnosed and treated at the ENT department of
      military hospital of Tunis. Clinical features, pH metric profiles and therapeutic
      approach are reported and compared to the literature. RESULTS: The mean age was
      37 years old. Sex ratio was 1.16. Pharyngolaryngeal symptoms dominated ENT
      manifestations (41 cases). Laryngeal dyspnea, cough and dysphonia were predictive
      of danger. Positive pH metric rate collated to posterior laryngitis and
      pharyngitis were respectively 81.2% and 79.1%. Posterior laryngitis, dental
      erosion and chronic sinusitis, seem to have pejorative significance. CONCLUSION:
      Otorhinolaryngologist must think about asymptomatic reflux every time when
      chronic or recurrent ENT affection remain unexplained after complete clinical
      investigations. PH monitoring confirms gastroesophageal reflux disease.

PMID- 22481198
TI  - [Ligation of internal iliac arteries for severe hemorrhage in obstetric].
AB  - AIM: To assess the efficiency of arteries ligation in intractable obstetrical
      hemorrhage. METHODS: Prospective study which concerned 53 patients who underwent
      internal iliac arteries ligation for persistent and severe obstetrical hemorrhage
      from January 2007 to June 2010. RESULTS: The average age of patients was 29.3
      years. The mean parity was 2.2. Main etiology of hemorrhage were: uterine atony
      (62.2%), abruptio placentae (15.1%). Coagulation disorders and hypovolemic shock
      were observed respectively in 20.7 % and 37.7%. Blood transfusion was performed
      in all cases. Internal iliac arteries ligation allowed hemorrhage control in 90.5
      % of cases. In five cases a hysterectomy was necessary to control bleeding.. No
      peroperative complication were observed. CONCLUSION: Internal iliac arteries
      ligation is a prerequisite treatment of severe postpartum hemorrhage. It is a
      good alternative to arterial embolization.

PMID- 22481199
TI  - Dermatologic manifestations in inflammatory bowel disease in Tunisia.
AB  - BACKGROUND: Cutaneous manifestations are the most common extra intestinal
      manifestations associated with inflammatory bowel disease (IBD). AIM: To assess
      the epidemio-clinical profile of skin manifestations in IBD. METHODS: A
      prospective and descriptive study was conducted. We have examined skin, mucosa,
      hair and nails, of all patients with an IBD during one year. RESULTS: One hundred
      ninety-five patients were included. Crohn's disease (CD) was noted in 154 cases
      (79.8%), ulcerous rectocolitis (UC) in 39 cases (21.2%) and inclassable IBD in 2
      cases. Cutaneous manifestations were found in 91% of Crohn's patients and in 92%
      of UC patients. Granulomatous perianal skin lesions were the main cutaneous
      manifestations of CD (53%). The most common affected sites were ano-perineal
      fistulae, perianal and perineal fissures and oedematous and infiltrated perianal
      and genital plaques. Reactive lesions (Erythema nodosum, Pyoderma gangrenosum,
      Aphthous stomatitis) were noted in 14 cases. Skin manifestations due to
      malabsorption were also frequently observed (101 cases: 51.7%).Other dermatoses
      implicating various mechanisms such as psoriasis, alopecia areata, vitiligo,
      rosacea, lichen planus, were also noted. Adverse skin manifestations due to
      treatment (folliculitis, acne, macula-papular rash and DRESS syndrome) were
      present in 16 cases. CONCLUSION: Our series is characterized by a high frequency
      of cutaneous manifestations associated to IBD. A better recognition of these skin
      manifestations by the physician may improve their management.

PMID- 22481200
TI  - Aminoacidopathies and organic acidurias in Tunisia: a retrospective survey over
      23 years.
AB  - BACKGROUND: Inborn errors of metabolism are neglected in developing countries
      because they are not as common as infectious and nutritional disorders. In
      Tunisia, no information is available on the incidence and epidemiological
      features of these inherited metabolic diseases. AIMS: To precise the profile of
      aminoacidopathies other than phenylketonuria and organic acidurias and to
      estimate their incidences in Tunisia. METHODS: Between 1987 and 2009, our
      laboratory received 13171 requests for analysis of patients with symptoms
      suggestive of inborn errors of metabolism. For these cases, ion exchange
      chromatography of free amino acids was performed on amino acids analyser. Urinary
      organic acids profiles were determined by gas chromatography-mass spectrometry.
      RESULTS: Abnormal cases were 370 (2.8%), divided into 212 cases of
      aminoacidopathies (57.3%) and 158 cases of organic acidurias (42.7%). The most
      frequent aminoacidopathies, were maple syrup disease (32.5%), tyrosinemia type I
      (28.8%) and nonketotic hyperglycinemia (16%). Methylmalonic aciduria (33.5%),
      propionic aciduria (18.4%) and 2-hyrdoxy glutaric aciduria (10.8%) were the most
      frequent organic acidurias. The incidences were calculated using the Hardy
      Weinberg formula and were estimated at 1/13716 for maple syrup disease, 1/14804
      for tyrosinemia type I, 1/16144 for methylmalonic aciduria and 1/23176 for
      propionic aciduria. CONCLUSION: Aminoacidopathies and organic acidurias turned
      out to be highly frequent in Tunisia, mainly because of a high rate of
      consanguinity. We believe that they are underestimated. To improve their
      diagnosis, it is necessary to have available sophisticated equipment which would
      allow early treatment of patients.

PMID- 22481201
TI  - [Primary peritonitis in previously healthy children].

PMID- 22481202
TI  - Coexistence of a malignant stromal tumor of the stomach with an adenocarcinoma of
      the lung in a patient with neurofibromatosis type 1.

PMID- 22481203
TI  - [Pancreatitis in systemic lupus erythematosus].

PMID- 22481204
TI  - Multiple eruptive milia in a 26 month-old boy.

PMID- 22481205
TI  - [Non calculous ureteral obstruction and Crohn's disease].

PMID- 22481206
TI  - Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by
      suppressing osteopontin.
AB  - Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However,
      the role of OPN in the development of acquired radioresistance in human lung
      cancer cells has not yet been fully elucidated. Therefore, the potential
      importance of OPN as a marker of lung cancer with a potential significant role in
      the development of radioresistance against repeated radiotherapy has prompted us
      to define the pathways by which OPN regulates lung cancer cell growth. In
      addition, autophagy has been reported to play a key role in the
      radiosensitization of cancer cells. Here, we report that increased OPN expression
      through induction of nuclear p53 following irradiation was inhibited by exogenous
      beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to
      induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our
      results suggest that the induction of autophagy abrogated the radioresistance of
      the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus
      mediated shRNA induced the autophagy of human lung cancer cell. Taken together,
      these results suggest that OPN and BECN1 can be molecular targets for overcoming
      radioresistance by controlling autophagy.

PMID- 22481207
TI  - Hydrology-linked spatial distribution of pesticides in a fjord system in
      Greenland.
AB  - A pilot study is presented evaluating selected chlorinated pesticides as chemical
      tracers for water masses in a sub-Arctic fjord system (Godthabsfjord, western
      Greenland). Polyoxymethylene (POM) based passive water samplers were deployed
      during summer-autumn 2010. The levels of the analysed chlorinated pesticides in
      the fjord surface waters were found to be low compared to earlier studies. alpha
      Hexachlorocyclohexane (alpha-HCH) and hexachlorobenzene (HCB) were the
      predominant contaminants. However, these two compounds have higher levels in
      oceanic water compared to freshwater influenced fjord waters. These chemicals can
      thus be considered as indicators for direct atmospheric long-range transport,
      while the organochlorine pesticides like trans-, cis-chlordane, trans-nonachlor
      and oxychlordane that are detected in the inner parts of the fjord are indicators
      for potential freshwater sources such as rivers and glacial meltwater runoff
      (secondary sources). The average values were 50 pg L(-1) for HCB and 11 pg L(-1)
      for alpha-HCH. These concentrations are comparable to levels in fjords in
      Svalbard (Norwegian Arctic), but lower than in open and/or ice covered oceans in
      the Canadian Arctic. Two air samplers were deployed for the identification of
      direct atmospheric contributions. Local contamination sources do not contribute
      significantly. The study demonstrated the value of passive water sampling devices
      for comprehensive hydrological characterization of Arctic coastal waters.

PMID- 22481208
TI  - Use of Solen brevis as a biomonitor for Cd, Pb and Zn on the intertidal zones of
      Bushehr-Persian Gulf, Iran.
AB  - The concentrations of Zn, Cd and Pb were determined in tissues (shell and soft
      tissue) of 144 of bivalve mollusks (Solen brevis) and 15 samples of surface
      sediment collected from three locations in intertidal zones of Bushehr coast,
      Persian Gulf, Iran in May 2011. The mean concentrations of Zn, Cd and Pb in the
      sediment samples were 26.2, 1.25, and 21.1 MUg/g dw, respectively. The mean
      levels of Zn, Cd and Pb in the clam samples were 63.3, 0.67, and 4.38 MUg/g dw in
      soft tissue and 10. 7, 1.53, and 15.6 MUg/g dw in shell, respectively. The
      degrees of variability (CV %) for Cd and Pb within the shells were lower than for
      soft tissues, whereas the CV for Zn was lower in the soft tissue than in the
      shell, indicating that there is more precision (lower CV) in the determination of
      Cd and Pb in the shells and Zn in the soft tissues. Significant correlation were
      found between Cd (r = 0.63; p < 0.05) and Pb (r = 0.78; p < 0.01) concentrations
      in the shell of S. brevis and their concentrations in the surface sediments.
      Indeed, Zn concentrations in the soft tissue of S. brevis significantly (r =
      0.63; p < 0.05) correlated with Zn concentrations in surface sediments. The
      results of this study suggest that the shell of S. brevis may serve as a reliable
      biomonitor for Cd and Pb, and the soft tissue for Zn.

PMID- 22481209
TI  - Trace element concentration in groundwater, Tuticorin city, Tamil Nadu, India.
AB  - The aim of the present study is to investigate the pollution vulnerability of
      groundwater aquifers in the coastal regions of Tuticorin city, Tamil Nadu, India.
      Fourteen samples were analyzed to determine the concentration of trace elements
      (Pb, Zn, Cd, Hg, Cr and Cu) in the groundwater. Among the total samples six were
      collected from industrial areas and eight from non-industrial areas of Tuticorin
      city. The concentration of trace element ranges from 0.01 to 0.19 mg/kg(-1) for
      Pb, from 0.01 to 0.16 mg/kg(-1) for Zn, from BDL to 0.21 mg/kg(-1) for Cd, from
      BDL (Below Detection Limit) to 0.023 mg/kg(-1) for Hg, from 0.02 to 0.18 mg/kg(
      1) for Cr and from 0.01 to 0.16 mg/kg(-1) for Cu. The trace element concentration
      in groundwater is higher than the WHO suggested maximum permissible limit except
      Zn and Cu.

PMID- 22481210
TI  - Application of different extraction methods for the determination of selected
      pesticide residues in sediments.
AB  - Using several extraction methods including the QuEChERS approach, samples of both
      model and natural sediments were prepared. For the isolation of the target group
      of pesticides, two variants of two complementary extractions had to be used.
      Resulting extracts were analysed with LC/MS/MS. Selected methods furnishing the
      best results were validated in the terms of linearity and repeatability. Their
      limits of detection ranged from 0.1 to 2 ng/g, their limits of quantification
      from 1 to 6 ng/g and their recovery percentage varied between 46 % and 102 %.

PMID- 22481211
TI  - Can a single-item measure assess physical load at work? An analysis from the
      GAZEL cohort.
AB  - OBJECTIVE: The assessment of workplace physical load is highly resource
      intensive. This study tested whether a single-item measure asking individuals
      about perceived physical strain (PPS) at work was an acceptable proxy for
      physical load. METHODS: The study was conducted in a subset of the GAZEL cohort
      (n = 2612) undergoing assessment of exposure to 38 occupational biomechanical
      constraints (representing eight domains) in 1994. Test-retest reliability
      analyses compared PPS in 1994 and 1995. Validity analyses compared PPS in 1994 to
      concurrent strains assessed in the more extensive measure. RESULTS: The measure
      showed adequate test-retest reliability. Within and across domains of physical
      load, linear relationships (P < 0.0001) existed between n exposures and PPS.
      Domains considered more strenuous (carrying loads, pulling objects) showed the
      highest PPS. CONCLUSIONS: Perceived physical strain approximates physical load in
      the absence of detailed measures. Perceived physical strain could be used in
      nonoccupational epidemiologic studies.

PMID- 22481212
TI  - Spatial distribution of spin polarization in a channel on the surface of a
      topological insulator.
AB  - We study the spatial distribution of electron spin polarization for a gate
      controlled T-shaped channel on the surface of a three-dimensional topological
      insulator (3D TI). We demonstrate that an energy gap depending on channel
      geometry parameters is definitely opened due to the spatial confinement. Spin
      surface locking in momentum space for a uniform wide channel with Hamiltonian
      linearity in the wavevector is still kept, but it is broken with Hamiltonian
      nonlinearity in the wavevector, like that for two-dimensional surface states
      widely studied in the literature. However, the spin surface locking for a T
      shaped channel is broken even with Hamiltonian linearity in the wavevector.
      Interestingly, the magnitude and direction of the in-plane spin polarization are
      spatially dependent in all regions due to the breaking of translational symmetry
      of the T-shaped channel system. These interesting findings for an electrically
      controlled nanostructure based on the 3D TI surface may be testable with the
      present experimental technique, and may provide further understanding the nature
      of 3D TI surface states.

PMID- 22481213
TI  - Report on the 12th symposium on invertebrate neurobiology held 31 August-4
      September 2011 at the Balaton Limnological Research Institute of the Hungarian
      Academy of Sciences, Tihany, Hungary.
AB  - In August 2011, the 12th international symposium of ISIN was held by Lake Balaton
      in Tihany, Hungary. This convivial and stimulating meeting provided a forum for
      discussion of a range of invertebrate organisms in neuroscience research. Here
      the main topics covered at the meeting are reviewed.

PMID- 22481214
TI  - Adults with cardiovascular disease who help others: a prospective study of health
      outcomes.
AB  - Little is known about the health impact of helping behaviors among individuals
      with high-risk chronic diseases such as cardiovascular disease (CVD). Using a
      nationally representative, longitudinal survey, we examined the subsequent health
      of adults with CVD (n = 4,491) who spent time providing non-paid assistance to
      family and friends outside of their households compared with those who had
      provided no assistance. After both adjusting for baseline characteristics and
      using propensity score matching methods, spending up to 200 h over the prior 12
      months helping others was associated with lower odds of experiencing a new CVD
      event or dying in the subsequent 2 years. Providing up to 100 h of assistance was
      associated with reporting fewer depressive symptoms. This threshold effect raises
      the question of whether assistance beyond a certain number of hours may impose a
      burden that mitigates health benefits from helping others. Health care providers
      could play an important role exploring ways that patients with CVD can provide
      beneficial levels of assistance to others in their own social networks or
      communities, thereby possibly also improving their own health.

PMID- 22481215
TI  - The relationship between body composition and bone mineral density in
      postmenopausal Turkish women.
AB  - In a retrospective cross-sectional study among 202 postmenopausal women aged 46
      75 years, we aimed to investigate the relationship between body composition and
      bone mineral density (BMD) to determine whether fat mass or lean mass is a better
      determinant of BMD in Turkish postmenopausal women. Lumbar spine (L1-L4) and
      proximal femur BMD were measured by dual energy X-ray absorbsiometry. Body
      composition analysis was performed by bioelectric impedance method and fat mass,
      lean mass, and percent fat were measured. Both fat mass and lean mass were
      positively correlated with BMD at the lumbar spine and proximal femur, weight and
      body mass index. Lean mass was also positively correlated with height and
      negatively correlated with age and years since menopause (P < 0.01). The
      correlations of fat mass and lean mass with BMD at the lumbar spine and proximal
      femur remained significant after adjustment for age, years since menopause and
      height. When the lean mass was adjusted together with age, years since menopause
      and height, the significant relationship between the fat mass and BMD continued,
      however the significant correlation between the lean mass and BMD disappeared at
      all sites after adjustment for fat mass. In multiple regression analyses, fat
      mass was the significant determinant of all BMD sites. Our data suggest that fat
      mass is the significant determinant of BMD at the lumbar spine and proximal
      femur, and lean mass does not have an impact on BMD when fat mass was taken into
      account in Turkish postmenopausal women.

PMID- 22481216
TI  - PR3 antibodies do not induce renal pathology in a novel PR3-humanized mouse model
      for Wegener's granulomatosis.
AB  - Different murine models have been used as basis for Proteinase 3 (PR3)-associated
      vasculitis models, but sufficient reproduction of the human clinical
      manifestation has failed to this date. As a reliable animal model is needed to
      further elucidate the pathological value of PR3-ANCA, we developed a PR3
      humanized transgenic mouse model, in order to induce a glomerulonephritis. Our
      huPR3-transgenic mice were injected i.v. with our monoclonal antibodies, either
      unlabeled or directly labeled by fluorescein isothiocyanate. For a period of 5
      days, proteinuria and erythrocyte count were measured with urine dip sticks. None
      of the mice exhibited proteinuria and/or an abnormal number of erythrocytes in
      the urine. Five days after antibody treatment, the mice were killed and different
      organs were fixed and immunohistochemically assessed. In the case of the kidney,
      we could detect a glomerulonephritis. Our study is able to show that although a
      direct renal target was given in transgenic human PR3 mice, no renal pathology
      was detectable. Multifactorial mechanisms for PR3-ANCA involvement in the
      development of Wegener's granulomatosis must be hypothesized.

PMID- 22481217
TI  - The crystalline state of methylene blue: a zoo of hydrates.
AB  - A re-investigation of the crystalline state of methylene blue has led to the
      identification of five different hydrates with clearly distinct structures. These
      include the already known pentahydrate, a hydrate with 2.2-2.3 equivalents of
      water, two dihydrates, and a monohydrate. Contrary to older reports, no
      trihydrate was found. The preparation and characterization of the hydrates as
      well as the transformations between them are reported. The applied analytical
      methods include X-ray powder diffraction (XRPD), infrared spectroscopy (ATR-IR),
      thermogravimetry (TGA), differential scanning calorimetry (DSC), dynamic water
      vapor sorption (DVS) and solution calorimetry (SolCal). A phase diagram of
      temperature vs. composition has been established, and the stability domains of
      the different hydrates as a function of water activity and temperature have been
      determined based on data from DSC, SolCal and suspension equilibration
      experiments. Four out of the five hydrates are thermodynamically stable within a
      certain range of temperature and humidity.

PMID- 22481218
TI  - Temporal profile of the singlet oxygen emission endogenously produced by
      photosystem II reaction centre in an aqueous buffer.
AB  - The temporal profile of the phosphorescence of singlet oxygen endogenously
      photosensitized by photosystem II (PSII) reaction centre (RC) in an aqueous
      buffer has been recorded using laser excitation and a near infrared
      photomultiplier tube. A weak emission signal was discernible, and could be fitted
      to the functional form a[exp(-t/tau(2) - exp(-t/tau(1)], with a > 0 and tau(2) >
      tau(1). The value of tau(2) decreased from 11.6 +/- 0.5 MUs under aerobic
      conditions to 4.1 +/- 0.2 MUs in oxygen-saturated samples, due to enhanced
      bimolecular quenching of the donor triplet by oxygen, whereas that of tau(1),
      identifiable with the lifetime of singlet oxygen, was close to 3 MUs in both
      cases. Extrapolations based on the low amplitude of the emission signal of
      singlet oxygen formed by PSII RC in the aqueous buffer and the expected values of
      tau(1) and tau(2) in chloroplasts indicate that attempts to analyse the temporal
      profile of singlet oxygen in chloroplasts are unlikely to be rewarded with
      success without a significant advance in the sensitivity of the detection
      equipment.

PMID- 22481219
TI  - Spectrally and spatially resolved cathodoluminescence of nanodiamonds: local
      variations of the NV(0) emission properties.
AB  - Here we report the spectrally and spatially resolved cathodoluminescence of
      diamond nanoparticles using focused fast electron beams in a transmission
      electron microscope. We demonstrate the possibility of quickly detecting various
      individual colour centres of different kinds on wide areas (several micrometres
      square) contained in nanoparticles separated by subwavelength distances. Among
      them, nanoparticles containing one or more neutral nitrogen-vacancy (NV(0))
      intensity maxima have been seen, attributable to individual emitters. Thanks to a
      spatial resolution which is solely limited by charge carrier diffusion in the
      case of a fast electron (80 keV) setup, the spectra of two individual NV(0)
      emitters separated by 80 nm inside a nanoparticle have been spatially discerned.
      A shift of the zero phonon line (ZPL) between the two emitters, which we
      attribute to internal stress, is shown to arise even within the same
      nanoparticle. Detailed emission spectra (ZPL, phonon lines and Huang-Rhys factor,
      directly linked to the relaxation energy of the colour centre) in 51 individual
      NV(0) centres have been measured in 39 particles. The ZPL and Huang-Rhys factor
      are found to be measurably dispersed, while the phonon energies keep constant.

PMID- 22481220
TI  - Vertical transmission of Brucella abortus causes sterility in pregnant mice.
AB  - The mechanisms of abortion and sterility induced by bacterial infection are
      largely unknown. In the present study, we found that Brucella abortus, a
      causative agent of brucellosis and facultative intracellular pathogen, caused
      sterility in pregnant mice. We have recently established a mouse model for
      abortion induced by B. abortus infection and high rates of abortion are observed
      for bacterial infection on day 4.5 of gestation, but not for other days. Infected
      newborn (first generation) mice showed poor growth compared with uninfected
      newborn mice and bacterial replication in the spleen of the former was observed
      over a long period. When infected first generation female mice were mated to
      infected first generation male mice, the number of fetuses was significantly less
      than that in uninfected first generation mice. These infected second generation
      mice also showed poor growth. These results suggest that vertical transmission of
      B. abostus causes sterility in pregnant mice and our mouse model would be useful
      for the investigating of brucellosis.

PMID- 22481221
TI  - Bibliography-editors' selection of current world literature.

PMID- 22481222
TI  - Interface biquadratic coupling and magnon scattering in exchange-biased
      ferromagnetic thin films grown on epitaxial FeF2.
AB  - The magnetic anisotropy of ferromagnetic (FM) Ni, Co, and Fe polycrystalline thin
      films grown on antiferromagnetic (AF) FeF(2)(110) epitaxial layers was studied,
      as a function of temperature, using ferromagnetic resonance. In addition to an in
      plane anisotropy in the FM induced by fluctuations in the AF short-range order, a
      perpendicular (biquadratic) magnetic anisotropy, with an out-of-plane component,
      was found which increased with decreasing temperature above the AF Neel
      temperature (T(N) = 78.4 K). This is a surprising result given that the AF's
      uniaxial anisotropy axis was in the plane of the sample, but is consistent with
      prior experimental and theoretical work. The resonance linewidth had a strong
      dependence on the direction of the external magnetic field with respect to in
      plane FeF(2) crystallographic directions, consistent with interface magnon
      scattering due to defect-induced demagnetizing fields. Below T(N), the exchange
      bias field H(E) measured via FMR for the Ni sample was in good agreement with
      H(E) determined from magnetization measurements if the perpendicular out-of-plane
      anisotropy was taken into account. A low field resonance line normally observed
      at H ~ 0, associated with domain formation during magnetization in ferromagnets,
      coincided with the exchange bias field for T < T(N), indicating domain formation
      with the in-plane FM magnetization perpendicular to the AF easy axis. Thus,
      biquadratic FM-AF coupling is important at temperatures below and above T(N).

PMID- 22481223
TI  - Experiment and mathematical modeling of gene expression dynamics in a cell-free
      system.
AB  - Cell-free in vitro expression is increasingly important for high-throughput
      expression screening, high yield protein production and synthetic biology
      applications. Yet its potential for quantitative investigation of gene expression
      and regulatory circuits is limited by the availability of data on composition,
      kinetic rate constants and standardized computational tools for modeling. Here we
      report on calibration measurements and mathematical modeling of a reconstituted
      in vitro expression system. We measured a series of GFP expression and mRNA
      transcription time courses under various initial conditions and established the
      translation step as the bottle neck of in vitro protein synthesis. Cell-free
      translation was observed to expire after 3 h independent of initial template DNA
      concentration. We developed a minimalistic rate equation model and optimized its
      parameters by performing a concurrent fit to measured time courses. The model
      predicts the dependence of protein yield not only on template DNA concentration,
      but also on experimental timing and hence is a valuable tool to optimize yield
      strategies.

PMID- 22481224
TI  - Perception of non-invasive ventilation in adult Swiss intensive care units.
AB  - The real utilisation scenario of non-invasive ventilation (NIV) in Swiss ICUs has
      never been reported. Using a survey methodology, we developed a questionnaire
      sent to the directors of the 79 adult ICUs to identify the perceived pattern of
      NIV utilisation. We obtained a response rate of 62%. The overall utilisation rate
      for NIV was 26% of all mechanical ventilations, but we found significant
      differences in the utilisation rates among different linguistic areas, ranging
      from 20% in the German part to 48% in the French part (p <0.01). NIV was mainly
      indicated for the acute exacerbations of COPD (AeCOPD), acute cardiogenic
      pulmonary edema (ACPE) and acute respiratory failure (ARF) in selected do-not
      intubate patients. In ACPE, CPAP was much less used than bi-level ventilation and
      was still applied in AeCOPD. The first line interface was a facial mask (81%) and
      the preferred type of ventilator was an ICU machine with an NIV module (69%). 
      The perceived use of NIV is generally high in Switzerland, but regional
      variations are remarkable. The indications of NIV use are in accordance with
      international guidelines. A high percentage of units consider selected do-not
      intubate conditions as an important additional indication.

PMID- 22481225
TI  - The development of the collagen fibre network in tissue-engineered cartilage
      constructs in vivo. Engineered cartilage reorganises fibre network.
AB  - For long term durability of tissue-engineered cartilage implanted in vivo, the
      development of the collagen fibre network orientation is essential as well as the
      distribution of collagen, since expanded chondrocytes are known to synthesise
      collagen type I. Typically, these properties differ strongly between native and
      tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study
      with implanted tissue-engineered cartilage in pigs were surprisingly good. The
      purpose of this study was therefore to analyse if the structure and composition
      of the artificial cartilage tissue changes in the first 52 weeks after
      implantation. Thus, collagen network orientation and collagen type distribution
      in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of
      Gottinger minipigs for 2, 26 or 52 weeks have been further investigated by
      processing digitised microscopy images of histological sections. The comparison
      to native cartilage demonstrated that fibre orientation over the cartilage depth
      has a clear tendency towards native cartilage with increasing time of
      implantation. After 2 weeks, the collagen fibres of the superficial zone were
      oriented parallel to the articular surface with little anisotropy present in the
      middle and deep zones. Overall, fibre orientation and collagen distribution
      within the implants were less homogenous than in native cartilage tissue. Despite
      a relatively low number of specimens, the consistent observation of a continuous
      approximation to native tissue is very promising and suggests that it may not be
      necessary to engineer the perfect tissue for implantation but rather to provide
      an intermediate solution to help the body to heal itself.

PMID- 22481226
TI  - Influence of in vitro maturation of engineered cartilage on the outcome of
      osteochondral repair in a goat model.
AB  - This study was designed to determine if the maturation stage of engineered
      cartilage implanted in a goat model of cartilage injury influences the repair
      outcome. Goat engineered cartilage was generated from autologous chondrocytes
      cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre
      culture and implanted above hydroxyapatite/hyaluronic acid sponges into
      osteochondral defects. Control defects were left untreated or treated with cell
      free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months
      post implantation by histological staining, modified O'Driscoll scoring and
      biochemical analyses. Increasing pre-culture time resulted in progressive
      maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the
      repair was not improved by any treatment. After 8 months, O'Driscoll histology
      scores indicated poor cartilage architecture for untreated (29.7 +/- 1.6) and
      cell-free treated groups (24.3 +/- 5.8). The histology score was improved when
      cellular grafts were implanted, with best scores observed for grafts pre-cultured
      for 2 weeks (16.3 +/- 5.8). As compared to shorter pre-culture times, grafts
      cultured for 6 weeks (histology score: 22.3 +/- 6.4) displayed highest type II/I
      collagen ratios but also inferior architecture of the surface and within the
      defect, as well as lower integration with native cartilage. Thus, pre-culture of
      engineered cartilage for 2 weeks achieved a suitable compromise between tissue
      maturity and structural/integrative properties of the repair tissue. The data
      demonstrate that the stage of development of engineered cartilage is an important
      parameter to be considered in designing cartilage repair strategies.

PMID- 22481227
TI  - Asynchrony, neural drive, ventilatory variability and COMFORT: NAVA versus
      pressure support in pediatric patients. A non-randomized cross-over trial.
AB  - PURPOSE: To determine if neurally adjusted ventilatory assist (NAVA) improves
      asynchrony, ventilatory drive, breath-to-breath variability and COMFORT score
      when compared to pressure support (PS). METHODS: This is a non-randomized short
      term cross-over trial in which 12 pediatric patients with asynchrony (auto
      triggering, double triggering or non-triggered breaths) were enrolled. Four
      sequential 10-min periods of data were recorded after 20 min of ventilatory
      stabilization (wash-out) at each of the following settings: baseline PS with the
      ventilator settings determined by the attending physician (1-PS(b)); PS after
      optimization (2-PS(opt)); NAVA level set so that maximum inspiratory pressure
      (P(max)) equaled P(max) in PS (3-NAVA); same settings as in 2-PS(opt) (4
      PS(opt)). RESULTS: The median asynchrony index was significantly lower during
      NAVA (2.0%) than during 2-PS(opt) (8.5%, p = 0.017) and 4-PS(opt) (7.5%, p =
      0.008). In NAVA mode, the NAVA trigger accounted on average for 66% of triggered
      breaths. The median trigger delay with respect to neural inspiratory time was
      significantly lower during NAVA (8.6%) than during 2-PS(opt) (25.2%, p = 0.003)
      and 4-PS(opt) (28.2%, p = 0.0005). The median electrical activity of the
      diaphragm (EAdi) change during trigger delay normalized to maximum inspiratory
      EAdi difference was significantly lower during NAVA (5.3%) than during 2-PS(opt)
      (21.7%, p = 0.0005) and 4-PS(opt) (24.6%, p = 0.001). The coefficient of
      variation of tidal volume was significantly higher during NAVA (44.2%) than
      during 2-PS(opt) (19.8%, p = 0.0002) and 4-PS(opt) (23.0%, p = 0.0005). The
      median COMFORT score during NAVA (15.0) was lower than that during 2-PS(opt)
      (18.0, p = 0.0125) and 4-PS(opt) (17.5, p = 0.039). No significant changes for
      any variable were observed between 1-PS(b) and 2-PS(opt). CONCLUSIONS: Neurally
      adjusted ventilatory assist as compared to optimized PS results in improved
      synchrony, reduced ventilatory drive, increased breath-to-breath mechanical
      variability and improved patient comfort.

PMID- 22481228
TI  - Multiscale modeling of platelet adhesion and thrombus growth.
AB  - Our hemostatic system, when called to action, depends on the complex arrangement
      of a tightly regulated and extensive network of molecules with versatile
      functionality. Experimental methods have demonstrated marked improvement through
      enhanced condition-control and monitoring. However, this approach continues to
      provide limited explanations of the role of individual elements or of a specific
      component within the entire system. To fill this void, multiscale simulations
      based on high throughput computing and comprehensive mathematical models are
      showing their strength in not only revealing hidden physiological mechanisms but
      also predicting pharmacological/phenotypical outcome in hemostasis reactions
      based on quantitative analysis. In this review article, we present up-to-date
      computational methods that simulate the process of platelet adhesion and thrombus
      growth, compare and summarize their advantages and drawbacks, verify their
      predictive power, and project their future directions. We provide an in-depth
      summary of one such computational method-Platelet Adhesive Dynamics (PAD)-and
      discuss its application in simulating platelet aggregation and thrombus
      development.

PMID- 22481229
TI  - Functional recovery of the dentate gyrus after a focal lesion is accompanied by
      structural reorganization in the adult rat.
AB  - The adult brain is highly plastic and tends to undergo substantial reorganization
      after injury to compensate for the lesion effects. It has been shown that such
      reorganization mainly relies on anatomical and biochemical modifications of the
      remaining cells which give rise to a network rewiring without reinstating the
      original morphology of the damaged region. However, few studies have analyzed the
      neurorepair potential of a neurogenic structure. Thus, the aim of this work was
      to analyze if the DG could restore its original morphology after a lesion and to
      establish if the structural reorganization is accompanied by  behavioral and
      electrophysiological recovery. Using a subepileptogenic injection of kainic acid
      (KA), we induced a focal lesion in the DG and assessed in time (1) the loss and
      recovery of dependent and non dependent DG cognitive functions, (2) the
      anatomical reorganization of the DG using a stereological probe and
      immunohistochemical markers for different neuronal maturation stages and, (3)
      synaptic plasticity as assessed through the induction of in vivo long-term
      potentiation (LTP) in the mossy fiber pathway (CA3-DG). Our results show that a
      DG focal lesion with KA leads to a well delimited region of neuronal loss,
      disorganization of the structure, the loss of associated mnemonic functions and
      the impairment to elicit LTP. However, behavioral and synaptic plasticity
      expression occurs in a time dependent fashion and occurs along the morphological
      restoration of the DG. These results provide novel information on neural
      plasticity events associated to functional reorganization after damage.

PMID- 22481230
TI  - Valence-specific laterality effects in vocal emotion: interactions with stimulus
      type, blocking and sex.
AB  - Valence-specific laterality effects have been frequently obtained in facial
      emotion perception but not in vocal emotion perception. We report a dichotic
      listening study further examining whether valence-specific laterality effects
      generalise to vocal emotions. Based on previous literature, we tested whether
      valence-specific laterality effects were dependent on blocked presentation of the
      emotion conditions, on the naturalness of the emotional stimuli, or on listener
      sex. We presented happy and sad sentences, paired with neutral counterparts,
      dichotically in an emotion localisation task, with vocal stimuli being preceded
      by verbal labels indicating target emotions. The measure was accuracy. When
      stimuli of the same emotion were presented as a block, a valence-specific
      laterality effect was demonstrated, but only in original stimuli and not morphed
      stimuli. There was a separate interaction with listener sex. We interpret our
      findings as suggesting that the valence-specific laterality hypothesis is
      supported only in certain circumstances. We discuss modulating factors, and we
      consider whether the mechanisms underlying those factors may be attentional or
      experiential in nature.

PMID- 22481231
TI  - Novel promoters that induce specific transgene expression during the green to
      ripening stages of tomato fruit development.
AB  - Fruit-specific promoters have been used as genetic engineering tools for studies
      on molecular mechanism of fruit development and advance in fruit quality and
      additional value by increasing functional component. Especially fruit-ripening
      specific promoters have been well utilized and studied in tomato; however, few
      studies have reported the development of promoters that act at fruit developing
      stages such as immature green and mature green periods. In this study, we report
      novel promoters for gene expression during the green to ripening stages of tomato
      fruit development. Genes specifically expressed at tomato fruit were selected
      using microarray data. Subsequent to confirmation of the expression of the
      selected 12 genes, upstream DNA fragments of the genes LA22CD07,
      Les.3122.2.A1_a_at and LesAffx.6852.1.S1_at which specifically expressed at fruit
      were isolated from tomato genomic DNA as promoter regions. Isolated promoter
      regions were fused with the GUS gene and the resultant constructs were introduced
      into tomato by agrobacterium-mediated transformation for evaluation of promoter
      activity in tomato fruit. The two promoters of LA22CD07, and LesAffx.6852.1.S1_at
      showed strong activity in the fruit, weak activity in the flower and undetectable
      activity in other tissues. Unlike well-known fruit-ripening specific promoters,
      such as the E8 promoter, these promoters exhibited strong activity in green fruit
      in addition to red-ripening fruit, indicating that the promoters are suitable for
      transgene expression during green to ripening stages of tomato fruit development.
      KEY MESSAGE: Novel fruit-specific promoters have been identified and are suitable
      for transgene expression during green to ripening stages of tomato fruit
      development.

PMID- 22481233
TI  - Prognostic significance of TAZ expression in resected non-small cell lung cancer.
AB  - INTRODUCTION: Transcriptional coactivator with PDZ-binding motif (TAZ) is known
      to bind to a variety of transcription factors to control cell differentiation and
      organ development. Recently, TAZ has been identified as an oncogene and has an
      important role in tumorigenicity of non-small cell lung cancer (NSCLC).
      Therefore, TAZ may present a novel target for the future diagnosis, prognosis,
      and therapy for lung cancer. We investigated the relationship between TAZ
      expression and clinicopathological parameters and determined its prognostic
      significance concerning survival in patients with resected NSCLC. METHODS: TAZ
      expression was immunohistochemically studied in 181 consecutive patients with
      NSCLC and 20 cases of normal lung tissue. The association between expression of
      TAZ and clinicopathological parameters was evaluated. Kaplan-Meier survival
      analysis and Cox proportional hazards models were used to estimate the effect of
      TAZ expression on survival. RESULTS: TAZ expression was observed in 121 of the
      181 (66.8%) NSCLC. TAZ had nuclear and cytoplasmic expression.
      Clinicopathologically, TAZ expression was significantly associated with lung
      adenocarcinoma (p = 0. 002), poorer differentiation (p = 0.001), p-tumor, node,
      metastasis stage (p = 0.001), lymph node metastasis (p = 0.032), intratumoral
      vascular invasion (p = 0.004), pleural invasion (p = 0.003), adjuvant
      chemotherapy (p = 0.044), and poorer prognosis (p = 0.002). Multivariable
      analysis confirmed that TAZ expression increased the hazard of death after
      adjusting for other clinicopathological factors (hazard ratio, 2.56; 95%
      confidence interval, 1.39-4.66; p = 0.01). Overall survival was significantly
      prolonged in TAZ negative group when compared with TAZ positive group (61.8
      versus 47.1 months; p < 0.0001), as was disease-free survival (44.3 versus 25.1
      months; p < 0.0001). Adjuvant chemotherapy prolonged overall survival among
      resected NSCLC patients with TAZ positive expression (p = 0.001). CONCLUSIONS:
      This study suggests that TAZ expression is a prognostic indicator of poorer
      survival probability for patients with resected NSCLC.

PMID- 22481234
TI  - What is the most effective follow-up model for lung cancer patients? A systematic
      review.
AB  - INTRODUCTION: In the U.K. more than 40,000 people are diagnosed with lung cancer
      every year and an estimated 65,000 people are living with lung cancer. The most
      effective follow-up strategy for these patients is undetermined. This article
      reports a systematic review of studies comparing different follow-up strategies
      for patients with lung cancer. METHODS: We searched Medline, Premedline, Embase,
      Cochrane Library, Cinahl, BNI, Psychinfo, Amed, Web of Science (SCI & SSCI), and
      Biomed Central and included any original study published in English comparing one
      type of follow-up strategy to another in patients with lung cancer who had
      received treatment with curative or palliative intent and/or best supportive
      care. Studies were included if there were 50 patients or more per follow-up
      group. RESULTS: Of the four included studies that compared different follow-up
      strategies in patients with lung cancer, one was a randomized controlled trial
      and three were retrospective. The studies all examined different follow-up
      strategies and tended to be marked by various limitations. No formal data
      synthesis was therefore possible. However, in one article there was some evidence
      that regular review was associated with less emergency-department crisis
      attendances than symptom-generated review. CONCLUSIONS: The included studies were
      marked by a number of methodological compromises. On the basis of the reported
      body of evidence it is therefore not possible to make any firm conclusions about
      the most effective follow-up strategy but the review has identified a need for
      urgent research into all aspects of follow-up.

PMID- 22481232
TI  - Histopathologic response criteria predict survival of patients with resected lung
      cancer after neoadjuvant chemotherapy.
AB  - INTRODUCTION: We evaluated the ability of histopathologic response criteria to
      predict overall survival (OS) and disease-free survival (DFS) in patients with
      surgically resected non-small cell lung cancer (NSCLC) treated with or without
      neoadjuvant chemotherapy. METHODS: Tissue specimens from 358 patients with NSCLC
      were evaluated by pathologists blinded to the patient treatment and outcome. The
      surgical specimens were reviewed for various histopathologic features in the
      tumor including percentage of residual viable tumor cells, necrosis, and
      fibrosis. The relationship between the histopathologic findings and OS was
      assessed. RESULTS: The percentage of residual viable tumor cells and surgical
      pathologic stage were associated with OS and DFS in 192 patients with NSCLC
      receiving neoadjuvant chemotherapy in multivariate analysis (p = 0.005 and p =
      0.01, respectively). There was no association of OS or DFS with percentage of
      viable tumor cells in 166 patients with NSCLC who did not receive neoadjuvant
      chemotherapy (p = 0.31 and p = 0.45, respectively). Long-term OS and DFS were
      significantly prolonged in patients who had <=10% viable tumor compared with
      patients with >10% viable tumor cells (5 years OS, 85% versus 40%, p < 0.0001 and
      5 years DFS, 78% versus 35%, p < 0.001). CONCLUSION: The percentages of residual
      viable tumor cells predict OS and DFS in patients with resected NSCLC after
      neoadjuvant chemotherapy even when controlled for pathologic stage.
      Histopathologic assessment of resected specimens after neoadjuvant chemotherapy
      could potentially have a role in addition to pathologic stage in assessing
      prognosis, chemotherapy response, and the need for additional adjuvant therapies.

PMID- 22481235
TI  - Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive
      treatment for locally advanced, unresectable esophageal cancer: a phase-II study
      of the SWOG (S0414).
AB  - INTRODUCTION: The specific aims of the study were to evaluate the 2-year overall
      survival (OS) and progression-free survival (PFS), toxicity profile, and best
      objective response rate in patients with locally advanced, clinically
      unresectable esophageal cancer receiving cetuximab, cisplatin, irinotecan, and
      thoracic radiotherapy (TRT) within a multi-institutional cooperative-group
      setting. METHODS: Eligible patients (cT4 M0 or medically unresectable, biopsy
      proven, and noncervical esophageal cancer) were to receive four 21-day cycles of
      cetuximab 400 mg/m (day 1, cycle 1), cetuximab 250 mg/m (day 8, 15, cycle 1; then
      days 1, 8, and 15 for subsequent cycles), cisplatin 30 mg/m (days 1 and 8, all
      cycles), and irinotecan 65 mg/m (days 1 and 8, all cycles). TRT was administered
      at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, to begin with on day
      1 of cycle 3. The primary endpoint was 2-year OS, with an accrual goal of 75
      patients with adenocarcinoma. RESULTS: The study was closed because of slow
      accrual, with 21 eligible patients (11 squamous, 10 adenocarcinoma) enrolled from
      May 2005 to September 2007. Two-year OS and PFS (95% confidence interval [CI])
      were 33.3% (14.6-57.0%) and 23.8% (8.2-47.2%), respectively. Kaplan-Meier
      estimates of median (95% CI) OS and PFS were 11.2 (6.4-43.6) and 6.4 (3.7-12.0)
      months, respectively. The overall response rate (95% CI) among 17 evaluable
      patients was 17.6% (3.8-43.4%), including 6% confirmed complete responders and
      12% unconfirmed partial responders. Two deaths resulted from protocol treatment
      (sudden death and gastrointestinal necrosis). Ten (47.6%) and 6 (28.6%) patients
      had grade-3 or -4 toxicity, respectively: 52.4% were hematologic, 23.8% had
      fatigue, 19.0% had nausea, 19.0% had dehydration, and 19.0% had anorexia.
      CONCLUSIONS: Concomitant cetuximab, cisplatin, irinotecan, and TRT were poorly
      tolerated in the first North American cooperative group trial testing this
      regimen for locally advanced esophageal cancer as treatment-related mortality
      approached 10%. Single-institution phase-II cetuximab-based combined modality
      trials have yielded encouraging results in preliminary analyses. The SWOG GI
      Committee endorses enrollment to open clinical trials to clarify the therapeutic
      ratio of cetuximab-based combined modality approaches for esophageal cancer.

PMID- 22481236
TI  - Zoledronic acid produces antitumor effects on mesothelioma through apoptosis and
      S-phase arrest in p53-independent and Ras prenylation-independent manners.
AB  - INTRODUCTION: We examined whether zoledronic acid (ZOL), the third generation of
      bisphosphonates, produced cytotoxic effects on human mesothelioma cells in vitro
      and in vivo, and investigated a possible involvement of p53, Ras, and
      extracellular signal-regulated kinase1/2 (ERK1/2) pathways. METHODS: Cytotoxicity
      and cell cycles were assessed with a colorimetric assay and flow cytometry,
      respectively. Expression levels of apoptosis-linked proteins and prenylation of
      small guanine-nucleotide-binding regulatory proteins were tested with p53-small
      interfering RNA, an ERK kinase1/2-inhibitor, and prenyl alcohols. The antitumor
      activity was examined in an orthotopic animal model. RESULTS: ZOL treatments
      suppressed growth of mesothelioma cells bearing the wild-type p53 gene through
      apoptosis induction accompanied by activation of caspases, or S-phase arrest by
      up-regulated cyclin A and B1. ZOL induced p53 phosphorylation and subsequent
      activation of the downstream pathways. Down-regulated p53 expression with the
      small interfering RNA, however, showed that both apoptosis and S-phase arrest
      were irrelevant to the p53 activation. Geranylgeranyl but not farnesyl
      pyrophosphate inhibited ZOL-induced apoptosis and S-phase arrest, and the
      geranylgeraniol supplement decreased ZOL-mediated Rap1A but not Ras
      unprenylation. Inhibition of ERK1/2 pathways suppressed ZOL-induced apoptosis but
      not S-phase arrest. We further demonstrated that ZOL, administrated
      intrapleurally, inhibited the tumor growth in the pleural cavity. CONCLUSIONS:
      These data indicate that ZOL induces apoptosis or S-phase arrest, both of which
      are independent of p53 activation and Ras unprenylation, and suggest that ZOL is
      a possible therapeutic agent to mesothelioma partly through non-Ras- and ERK1/2
      mediated pathways.

PMID- 22481237
TI  - NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients
      with lung cancer.
AB  - OBJECTIVE: Expression of N-myc downstream-regulated gene 1 (NDRG1)/Cap43 is a
      prognostic indicator of human malignancies according to the tumor type in which
      it occurs. We investigated how NDRG1/Cap43 could affect tumor growth and
      angiogenesis in non-small-cell lung cancer (NSCLC) in vivo using an animal
      experimental model, and also how it could affect tumor angiogenesis and prognosis
      in NSCLC patients. METHODS AND RESULTS: Knockdown of NDRG1/Cap43 in lung cancer
      cells using a specific small interfering RNA resulted in growth rates in culture
      that were similar to those of counterpart control cells, but decreased tumor
      growth rates in vivo markedly. Stable NDRG1/Cap43 knockdown did not induce
      consistent changes in the expression of Epidermal growth factor receptor (EGFR)
      family proteins and c-Met in two human lung cancer cell lines in vitro. However,
      cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the
      potent angiogenic factors vascular endothelial growth factor-A and interleukin-8.
      Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced
      angiogenesis. Using immunohistochemistry, we examined 182 surgically resected
      specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis. High
      microvessel density in the tumor was significantly associated with nuclear
      positivity for NDRG1/Cap43 in both adenocarcinoma (p = 0.003) and squamous cell
      carcinoma (p=0.041). For both adenocarcinoma (p = 0.031) and squamous cell
      carcinoma (p=0.034), the survival curve of patients negative for nuclear
      NDRG1/Cap43 expression differed significantly from that of patients who were
      positive. CONCLUSION: Therefore, the expression of NDRG1/Cap43 may be predictive
      of tumor angiogenesis and poor prognosis in NSCLC.

PMID- 22481238
TI  - Surgical outcome of stage IIIA- cN2/pN2 non-small-cell lung cancer patients in
      Japanese lung cancer registry study in 2004.
AB  - BACKGROUND: The role of surgery in the treatment of non-small-cell lung cancer
      (NSCLC) with clinically manifested mediastinal node metastasis is controversial
      even in resectable cases because it is often accompanied by systemic
      micrometastasis. However, surgery is occasionally indicated for cases with single
      station N2 disease or within multimodal treatment regimens, and in clinical
      trials. The aim of this study is to evaluate surgical outcomes in a modern cohort
      of patients with clinical (c-) stage IIIA-N2 NSCLC whose nodal metastasis was
      confirmed by pathology (cN2/pN2). METHODS: From the central database of lung
      cancer patients undergoing surgery in 2004, which was founded by the Japanese
      Joint Committee for Lung Cancer Registration, data of patients having all
      conditions of NSCLC, c-stage IIIA, cN2, and pN2 were extracted, and the
      clinicopathologic profile of patients and surgical outcomes were evaluated.
      RESULTS: Among 11,663 registered NSCLC cases, 436 patients (3.8%) (332 men and
      104 women) had been extracted. Their mean age was 65 years, and histologic types
      included adenocarcinoma (n = 246), squamous cell carcinoma (n = 132), and others
      (n = 58). The proportion of R0 resection was 82.5% and the proportion of the
      hospital deaths among the cause of death was 2.3%. The 5-year survival rate was
      30.1% for the selected group of patients. The postoperative prognosis was
      significantly better than those of corresponding populations extracted from the
      1994 (p = 0.0001) and 1999 databases (p = 0.0411). Men and women experienced a
      significantly different survival outcome (p = 0.025) with 5-year survivals of
      27.5% and 37.8%, respectively. Single-station N2 cases occupied 60.9 % of the
      cohort and showed a significantly better prognosis than multistation N2 (p =
      0.0053, 35.8 % versus 22.0 % survival rate at 5 years). CONCLUSIONS: The surgical
      outcomes of c-stage IIIA-cN2/pN2 NSCLC patients in 2004 were favorable in
      comparison with those ever reported.

PMID- 22481239
TI  - Primary care medical provider attitudes regarding mental health and behavioral
      medicine in integrated and non-integrated primary care practice settings.
AB  - Primary care medical providers (PCPs) have become de facto providers of services
      for the management of both mental and chronic illnesses. Although some reports
      suggest that PCPs favor having Behavioral Health colleagues provide behavioral
      health services in primary care, others demonstrate this view is necessarily not
      universal. We examined attitudes regarding behavioral health services among PCPs
      in practices that offer such services via onsite behavioral health providers (n =
      31) and those that do not (n = 62). We compared referral rates and perceived need
      for and helpfulness of behavioral health colleagues in treating mental
      health/behavioral medicine issues. In both samples, perceived need was variable
      (5-100%), as were PCPs' views of their own competence in mental health/behavioral
      medicine diagnosis and treatment. Interestingly, neither sample rated perceived
      access to behavioral health providers exceptionally high. Referral rates and
      views about the helpfulness of behavioral health services, except in relation to
      depression and anxiety, were lower than expected. These results suggest a need
      for increased collaboration with and education of PCPs about the roles and skills
      of behavioral health professionals.

PMID- 22481240
TI  - Interprofessional education: preparing psychologists for success in integrated
      primary care.
AB  - Rapidly occurring changes in the healthcare arena mean time is of the essence for
      psychology to formalize a strategic plan for training in primary care settings.
      The current article articulates factors affecting models of integrated care in
      Academic Health Centers (AHCs) and describes ways to identify and utilize
      resources at AHCs to develop interprofessional educational and clinical
      integrated care opportunities. The paper asserts that interprofessional
      educational experiences between psychology and other healthcare providers are
      vital to insure professionals value one another's disciplines in health care
      reform endeavors, most notably the patient-centered initiatives. The paper
      highlights ways to create shared values and common goals between primary care
      providers and psychologists, which are needed for trainee internalization of
      integrated care precepts. A developmental perspective to training from pre
      doctoral, internship and postdoctoral levels for psychologists in integrated care
      is described. Lastly, a call to action is given for the field to develop more
      opportunities for psychology trainees to receive education and training within
      practica, internships and postdoctoral fellowships in primary care settings to
      address the reality that most patients seek their mental health treatment in
      primary care settings.

PMID- 22481241
TI  - Structure and electronic properties of the double-wall nanotubes constructed from
      SiO2 nanotubes encapsulated inside zigzag carbon nanotubes.
AB  - This paper presents ab initio self-consistent field crystal orbital calculations
      on the structures, stabilities, elastic and electronic properties of the double
      wall nanotubes made of SiO(2) nanotubes encapsulated inside zigzag carbon
      nanotubes based on density functional theory. It is found that formation of the
      combined systems is energetically favorable when the nearest distance between the
      two constituents is in the area of the van der Waals effect. The obtained band
      structures show that all the combined systems are semiconductors with nonzero
      energy gaps. Based on the deformation potential theory and effective mass
      approximation, the mobilities of charge carriers are calculated to be in the
      range of 10(2)-10(4) cm(2) V(-1) s(-1), the same order of magnitude as those of
      the corresponding zigzag carbon nanotubes. The Young's moduli are also calculated
      for the combined systems.

PMID- 22481242
TI  - Sparse sampling methods in multidimensional NMR.
AB  - Although the discrete Fourier transform played an enabling role in the
      development of modern NMR spectroscopy, it suffers from a well-known difficulty
      providing high-resolution spectra from short data records. In multidimensional
      NMR experiments, so-called indirect time dimensions are sampled parametrically,
      with each instance of evolution times along the indirect dimensions sampled via
      separate one-dimensional experiments. The time required to conduct
      multidimensional experiments is directly proportional to the number of indirect
      evolution times sampled. Despite remarkable advances in resolution with
      increasing magnetic field strength, multiple dimensions remain essential for
      resolving individual resonances in NMR spectra of biological macromolecues.
      Conventional Fourier-based methods of spectrum analysis limit the resolution that
      can be practically achieved in the indirect dimensions. Nonuniform or sparse data
      collection strategies, together with suitable non-Fourier methods of spectrum
      analysis, enable high-resolution multidimensional spectra to be obtained.
      Although some of these approaches were first employed in NMR more than two
      decades ago, it is only relatively recently that they have been widely adopted.
      Here we describe the current practice of sparse sampling methods and prospects
      for further development of the approach to improve resolution and sensitivity and
      shorten experiment time in multidimensional NMR. While sparse sampling is
      particularly promising for multidimensional NMR, the basic principles could apply
      to other forms of multidimensional spectroscopy.

PMID- 22481243
TI  - Risk for obstructive sleep apnea in obese, nondiabetic adults varies with insulin
      resistance status.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is an increasingly common sleep disorder,
      especially among obese adults. Early identification of adults at risk for OSA
      would be of substantial benefit; however, the magnitude of the obesity epidemic
      requires that screening be performed judiciously. The study's aim was to utilize
      questionnaires that assess OSA risk and symptoms to test the hypothesis that the
      most insulin-resistant subset of obese individuals is at highest risk for OSA.
      METHODS: Nondiabetic, overweight to obese volunteers underwent direct
      quantification of insulin sensitivity by measuring steady-state plasma glucose
      concentrations during the insulin suppression test. Insulin-sensitive and insulin
      resistant individuals were administered the Berlin and STOP questionnaires to
      determine OSA risk status, and Epworth Sleepiness Scale (ESS) to evaluate daytime
      sleepiness. Fasting insulin and lipid/lipoprotein measurements were performed.
      RESULTS: Insulin-mediated glucose disposal differed threefold (p < 0.001) between
      equally obese, insulin-resistant (n = 22) and insulin-sensitive (n = 14)
      individuals, associated with higher fasting insulin and triglyceride and lower
      high-density lipoprotein cholesterol (HDL-C) concentrations in insulin-resistant
      individuals. Fourteen (64 %) insulin-resistant as compared with 2 (14 %) insulin
      sensitive individuals were found to be at high risk for OSA by both
      questionnaires (p < 0.01). Whereas half of insulin-resistant individuals met the
      ESS criteria for excessive daytime sleepiness, only one insulin-sensitive
      individual did (p = 0.011). CONCLUSIONS: High risk for OSA and excessive daytime
      sleepiness is prevalent among the insulin-resistant subgroup of obese
      individuals. Surrogate estimates of insulin resistance based on fasting insulin,
      triglycerides, and/or HDL-C can be used to help identify those obese adults who
      would benefit most from OSA screening and referral for polysomnography.

PMID- 22481244
TI  - The absolute nucleated red blood cell (aNRBC) count at birth is not an indicator
      for retinopathy of prematurity (ROP).
AB  - OBJECTIVE: To establish the reproducibility of a published observation by
      Lubetzky et al. that infants affected by retinopathy of prematurity (ROP) had
      higher absolute nucleated red blood cell (aNRBC) counts than those unaffected.
      The authors suggested that infants exposed to intrauterine hypoxia are at higher
      risk for ROP. We attempted to verify this reported relationship of ROP with the
      aNRBCs at birth and hypothesized that infants with ROP >= stage 2 have higher
      aNRBCs at birth. STUDY DESIGN: We report a retrospective 1:1 case matched
      analysis where cases had a diagnosis of grade II ROP or worse and matching
      infants had confirmed stage I or no ROP. Eligible infants had birth weights of
      501 to 1500 g and were discharged alive from 1st January 2000 to 31st December
      2008. Wilcoxon's signed rank test was performed for continuous comparisons. This
      study was approved by two local Institutional Review Boards. RESULT: In all, 66
      matched pairs were analyzed. When comparing aNRBCs there was no statistically
      significant relationship (w=-0.265, P=0.791) between the ROP affected group
      (M=4550, s.d.=7342) and the unaffected group (M=5287, s.d.=6524). CONCLUSION: We
      are unable to support the previously reported relationship of aNRBCs with ROP.
      Our population was three times larger, had higher aNRBCs and less retinopathy
      than previously reported. A biological principle of cause and effect or
      predisposition to ROP as reflected by aNRBCs should have been easier for us to
      demonstrate, if it existed.

PMID- 22481245
TI  - Usefulness of serum lipid peroxide as a diagnostic test for hypoxic ischemic
      encephalopathy in the full-term neonate.
AB  - OBJECTIVE: To evaluate the usefulness of serum lipid peroxide (LPO) for hypoxic
      ischemic encephalopathy (HIE) in full-term neonates. STUDY DESIGN: Diagnostic
      test evaluation forming three groups: (1) healthy full-term neonates (n=59), (2)
      at-risk full-term neonates without HIE (n=57) and (3) at-risk full-term neonates
      with HIE (n=57). HIE diagnosis was made using the Finer clinical classification
      at 48 h after birth. Serum LPO was taken at 4 h after birth and determined by
      spectrophotometry. RESULT: One hundred seventy-three full-term neonates were
      studied. Fifty-one of the at-risk full-term neonates with HIE (51/57) had high
      serum LPO and two of the at-risk full-term neonates without HIE (2/57) (P<0.001).
      Serum LPO level had 89% sensitivity, 96% specificity, 96% positive predictive
      value, 90% negative predictive value, 24 positive probability ratio, 0.11
      negative probability ratio and 92% diagnostic usefulness. CONCLUSION: Serum LPO
      level could be a useful test for early diagnosis of HIE in full-term neonates.

PMID- 22481246
TI  - Improving adherence to antiretroviral therapy for youth living with HIV/AIDS: a
      pilot study using personalized, interactive, daily text message reminders.
AB  - BACKGROUND: For youth living with human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS), nonadherence to antiretroviral therapy (ART)
      can lead to poor health outcomes and significantly decreased life expectancy.
      OBJECTIVE: To evaluate the feasability, acceptability, and preliminary efficacy
      of short message service (SMS) or text message reminders to improve adherence to
      ART for youth living with HIV/AIDS. METHODS: We conducted this prospective pilot
      study using a pre-post design from 2009 to 2010 at a community-based health
      center providing clinical services to youth living with HIV/AIDS. Eligibility
      criteria included HIV-positive serostatus, age 14-29 years, use of a personal
      cell phone, English-speaking, and being on ART with documented poor adherence.
      During the 24-week study period, participants received personalized daily SMS
      reminders and a follow-up message 1 hour later assessing whether they took the
      medication, and asking participants to respond via text message with the number 1
      if they took the medication and 2 if they did not. Outcome measures were
      feasibility, acceptability, and adherence. Self-reported adherence was determined
      using the visual analog scale (VAS) and AIDS Clinical Trial Group (ACTG)
      questionnaire 4-day recall. Viral load and CD4 cell count were followed as
      biomarkers of adherence and disease progression at 0, 12, and 24 weeks. RESULTS:
      Participants (N = 25) were mean age 23 (range 14-29) years, 92% (n = 23) male,
      60% (n = 15) black, and 84% (n = 21) infected through unprotected sex. Mean VAS
      scores significantly increased at 12 and 24 weeks in comparison with baseline
      (week 0: 74.7, week 12: 93.3, P < .001; week 24: 93.1, P < .001). ACTG
      questionnaire 4-day recall also improved (week 0: 2.33, week 12: 3.24, P = .002;
      week 24: 3.19, P = .005). There was no significant difference in CD4 cell count
      or viral load between baseline and 12- or 24-week follow-up, although there was a
      trend toward improvement of these biomarkers and a small to moderate standardized
      effect size (range of Cohen d: -0.51 to 0.22). Of 25 participants, 21 (84%) were
      retained, and 20 of the 21 (95%) participants who completed the study found the
      intervention helpful to avoid missing doses. CONCLUSIONS: In this pilot study,
      personalized, interactive, daily SMS reminders were feasible and acceptable, and
      they significantly improved self-reported adherence. Larger controlled studies
      are needed to determine the impact of this intervention on ART adherence and
      other related health outcomes for youth living with HIV/AIDS.

PMID- 22481247
TI  - Risky communication in atherosclerosis and thrombus formation.
AB  - Atherosclerosis, a progressive disease of medium- and large-sized arteries,
      constitutes the major cause of death in developed countries, and is becoming
      increasingly prevalent in developing countries as well. The main consequences of
      atherosclerosis are myocardial infarction, cerebral infarction and aortic
      aneurysm. This inflammatory disease is characterised by specific intimal lesions
      where lipids, leukocytes and smooth muscle cells accumulate in the arterial wall
      over time. Risk factors for atherosclerosis can mainly be divided into two
      groups: i) risk factors induced by environment and behaviour (e.g., Western diet,
      smoking and sedentary lifestyle) and ii) genetic risk factors. Multiple
      epidemiological studies have associated a single nucleotide polymorphism (SNP) in
      the GJA4 gene, coding for connexin37 (Cx37), with increased risk for
      atherosclerosis and myocardial infarction. Connexins form gap junctions or hemi
      channels that mediate an exchange of factors between i) the cytosol of two
      adjacent cells or ii) the cytosol and the extracellular environment,
      respectively. The GJA4 SNP codes for a proline-to-serine substitution at amino
      acid 319 in the regulatory C-terminus of the Cx37 protein, thereby altering basic
      and regulatory properties of its gap junction- and hemi-channels. In this review
      we discuss current evidence for mechanisms that link the GJA4 SNP to
      atherosclerosis or thrombus formation after plaque rupture.

PMID- 22481248
TI  - TrAnsFuSE refines the search for protein function: oxidoreductases.
AB  - Non-equilibrium catalysis of electron transfer reactions (i.e. redox) regulates
      the flux of key elements found in biological macromolecules. The enzymes
      responsible, oxidoreductases, contain specific transition metals in poorly
      sequence-conserved domains. These domains evolved ~2.4 billion years ago in
      microbes and spread across the tree of life. We lack understanding of how
      oxidoreductases evolved; divergence of sequences makes identification difficult.
      We developed a method to recognise the various versions of these enzyme-domains
      in unannotated sequence-space. Often, homology is used to transfer function
      annotations from experimentally resolved domains to unannotated sequences.
      Unreliability of inferring homology below 30% sequence identity limits single
      sequence based searches. Misaligned functional sites may compromise annotation
      transfer from even very similar sequences. Combining profile-based searches with
      knowledge of functional sites could improve domain detection accuracy. Here we
      present an approach that enhances the search for redox domains using catalytic
      site annotations. From the scientific literature, we validated annotations of 104
      InterPro domains indicated as using "transition metals in redox reactions." These
      domains mediate electron transfer in 20% of oxidoreductases, primarily employing
      iron, copper and molybdenum. We used the experimentally identified catalytic
      residues in these domains to validate sequence alignment-based protein function
      annotations. Our method, TrAnsFuSE, is 11% and 14% more accurate than PSI-BLAST
      and InterPro, respectively. Moreover, it is robust for use with other functional
      residues-we attain higher accuracy at comparable coverage using metal binding, in
      addition to catalytic, sites. TrAnsFuSE can be used to focus the study of the
      vast amounts of unannotated sequencing data from meta-/genome projects.

PMID- 22481249
TI  - Anomalous response of supported few-layer hexagonal boron nitride to DC electric
      fields: a confined water effect?
AB  - We use electric force microscopy (EFM) to study the response of supported few
      layer hexagonal boron nitride (h-BN) to an electric field applied by the EFM tip.
      Our results show an anomalous behavior in the dielectric response of h-BN atop Si
      oxide for different bias polarities: for a positive bias applied to the tip, h-BN
      layers respond with a larger dielectric constant than the dielectric constant of
      the substrate, while for a negative bias, the h-BN dielectric constant appears to
      be smaller. Based on ab initio calculations, we propose that this behavior is due
      to a water layer confined between the Si oxide substrate and h-BN layers. This
      hypothesis was experimentally confirmed by sample annealing and also by a
      comparative analysis with h-BN on a non-polar substrate.

PMID- 22481250
TI  - Effects of ligand tuning on dinuclear indium catalysts for lactide
      polymerization.
AB  - Functionalized diaminophenols, H(N(R1R2)N(R3)O), were investigated as ligands for
      indium catalysts in the ring-opening polymerization of racemic lactide. Precursor
      complexes (N(Me2)N(Me)O)InCl(2) (1), (N(Pr2)NO)InCl(2) (2), and (N(Mes)NO)InCl(2)
      (3) were synthesized and fully characterized by (1)H and (13)C NMR spectroscopy,
      elemental analysis, and single-crystal X-ray crystallography. Complexes 1 and 2
      were used to synthesize alkoxy-bridged complexes [(N(Me2)N(Me)O)InCl](2)(MU
      Cl)(MU-OEt) (4) and [(N(Pr2)NO)InCl](2)(MU-Cl)(MU-OEt) (5). These complexes
      catalysed the polymerization of racemic lactide at different rates, with complex
      5 being substantially more active than complex 4. The dissociation behaviour of
      these catalysts in the presence of lactide was also studied and used to make
      comparisons with previously reported catalyst systems.

PMID- 22481251
TI  - The FGF2-binding peptide P7 inhibits melanoma growth in vitro and in vivo.
AB  - PURPOSE: Melanoma is a malignant tumor and causes majority of deaths related to
      skin cancer. Fibroblast growth factor 2 (FGF2) greatly contributes to melanoma
      growth and progress. In this paper, we attempt to evaluate the therapeutic
      potential of FGF2-binding peptide (named P7) using as a potent FGF2 antagonist
      via exploration of its antitumor effect on melanoma in vitro and in vivo.
      METHODS: Cell viability was measured by WST-1. Cell cycle progression was
      determined by propidium iodide staining and flow cytometry. Western blotting was
      carried out to detect the activation of Erk1/2, P38, Akt, and MEK, and the
      expression of apoptosis-associated proteins. The influence of P7 on FGF2
      internalization was assessed by separation of nuclear and cytoplasmic protein
      fractions followed by Western blotting. Female C57BL/6 mice bearing xenograft
      melanoma were established and used to evaluate the antitumor effect of P7 in
      vivo. RESULTS: In this study, we first proved that P7 peptides significantly
      inhibited proliferation of FGF2-induced melanoma cell line B16-F10. Further
      investigations revealed that the mechanisms of P7 peptides inhibiting cell
      proliferation of melanoma cells stimulated with FGF2 in vitro involved cell cycle
      arrest at the G0/G1 phase, blockade of the activation of Erk1/2, P38, and Akt
      cascades, and inhibition of FGF2 internalization. Finally, treatment of P7
      peptides in a murine melanoma model resulted in significant inhibition of tumor
      growth and angiogenesis in vivo, which was associated with blockade of mitogen
      activated protein kinase signal activation, and suppression of the expressions of
      anti-apoptotic Bcl-2 protein and angiogenic factor in the melanoma tumors.
      CONCLUSIONS: The FGF2-binding peptide with potent antiproliferation and anti
      angiogenic activity may have therapeutic potential in melanoma.

PMID- 22481252
TI  - Analysis of EGF+61A>G polymorphism and EGF serum levels in Brazilian glioma
      patients treated with perillyl alcohol-based therapy.
AB  - PURPOSE: Malignant gliomas are associated with alteration in EGF/EGFR signaling.
      Functional EGF+61A>G polymorphism is implicated with risk, recurrence, and
      progression of glioma. This study aimed to establish a putative association of
      EGF+61A>G with risk of glioma development, production of angiogenic growth factor
      EGF, and the response to perillyl alcohol administered by intranasal route.
      METHODS: The study included 83 patients with recurrent glioma enrolled in Phase
      I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n
      = 196) as control group. DNA was extracted from blood samples, EGF genotype
      performed with PCR-RFLP assay, and EGF circulating levels by enzyme immunoassay.
      Adequate statistical tests were performed to verify associations between
      polymorphism and glioma risk, and genotype correlation with EGF circulating
      levels. The log-rank test was also used to evaluate differences on patient
      survival. RESULTS: Patients with primary glioblastoma had high frequency of AA
      genotype (p = 0.037) and A allele (p = 0.037). Increased EGF circulating levels
      were observed in glioma patients with AA (p = 0.042), AG (p = 0.006), and AA + AG
      (p = 0.008) genotypes compared with GG. Patients with GG genotype showed
      increased but not significant (p > 0.05) survival rate, and EGF levels lower than
      250 pg/mL was consistently (p = 0.0374) associated with increased survival.
      CONCLUSION: Presence of EGF+61A>G polymorphism in Brazilian subjects was
      associated with glioma risk and increased circulating EGF levels. Better response
      to perillyl alcohol-based therapy was observed in a group of adult Brazilian
      subjects with lower EGF levels.

PMID- 22481253
TI  - Lentivirus-delivered ZEB-1 small interfering RNA inhibits lung adenocarcinoma
      cell growth in vitro and in vivo.
AB  - PURPOSE: To explore the relationship between the expression of ZEB1 gene and the
      proliferation ability of lung adenocarcinoma cells. METHODS:
      Immunohistochemistry, Western blot and Real-time PCR were used to detect the
      expression of ZEB1 gene in lung adenocarcinoma tissue and cell lines compared
      with adjacent noncancerous region and the human lung fibroblast cell HLF cells.
      The lentivirus RNA interference technique was used to knock down the expression
      of ZEB1 in lung adenocarcinoma A549 and H1299 cell lines. Cell cycle and cell
      apoptosis were measured by FCM assay. In vivo, four groups of 4-week-old nude
      mice were subcutaneously injected with the stably transfected (ZEB-si, scr-si)
      cells at a single site to investigate the effect of ZEB1-siRNA in the nude mice
      tumor growth. In situ apoptosis was detection by TUNEL assay. RESULTS: ZEB-1 was
      highly expressed in lung adenocarcinoma tissue and cell lines compared with
      adjacent noncancerous region and the human lung fibroblast cell HLF cells. ZEB1
      siRNA could decrease lung adenocarcinoma cell proliferation by delaying S-phase
      entry and induce cell apoptosis, which led to the inhibition of the
      tumorigenicity of A549 and H1299 cell lines. Further investigation showed that
      injecting the ZEB1-siRNA cells into the nude mice could significantly decrease
      the tumor growth. CONCLUSION: Knockdown of ZEB-1 expression by lentivirus
      delivered siRNA may provide a novel therapeutic target for the treatment of lung
      cancer.

PMID- 22481254
TI  - The PSCA polymorphisms derived from genome-wide association study are associated
      with risk of gastric cancer: a meta-analysis.
AB  - PURPOSE: Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol
      anchored 123-aa protein related to the cell-proliferation inhibition and/or cell
      death induction activity. Many studies had reported the role of PSCA rs2294008 C
      > T and rs2976392 G > A polymorphisms on gastric cancer risk. METHODS: To
      investigate a more precise estimation of the relationships, we performed a meta
      analysis on 9 case-control studies included 10,746 cases and 9,158 controls. Odds
      ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength
      of the association. RESULTS: For PSCA rs2294008 C > T polymorphism, there was a
      significantly increased risk of gastric cancer in all genetic models (TT/TC vs.
      CC: OR = 1.61, 95 % CI = 1.35-1.91; TT vs. TC/CC: OR = 1.33, 95 % CI = 1.24
      1.42). Similar results were also observed for PSCA rs2976392 G > A polymorphism
      (AA/AG vs. GG: OR = 1.69, 95 % CI = 1.24-2.31; AA vs. AG/GG: OR = 1.36, 95 % CI =
      1.24-1.50). In the stratified analysis by ethnicity of rs2294008, an increased
      gastric cancer risk was found in both Asians (TT vs. TC/CC: OR = 1.31, 95 % CI =
      1.22-1.42) and Europeans (TT/TC vs. CC: OR = 1.42, 95 % CI = 1.18-1.71).
      Furthermore, when stratified by clinicopathologic characteristics of tumor
      location and histology, a higher risk on non-cardia compared with cardia gastric
      cancer (TT vs. TC/CC: OR = 1.43, 95 % CI = 1.12-1.83) as same as diffused
      compared with intestinal gastric cancer (TT vs. TC/CC: OR = 1.29, 95 % CI = 1.13
      1.49) was observed. CONCLUSION: These findings supported that PSCA rs2294008 C >
      T and rs2976392 G > A polymorphisms may contribute to the susceptibility to
      gastric cancer, particular in non-cardia or diffused gastric cancer.

PMID- 22481255
TI  - [Hepatitis C as a metabolic disease].

PMID- 22481256
TI  - [Glucose metabolism disorder: a risk factor for hepatocellular carcinoma].

PMID- 22481257
TI  - [Lipid metabolism-related gene expression in hepatocellular carcinoma].

PMID- 22481258
TI  - [Hepatocarcinogenesis and iron metabolic disorder].

PMID- 22481259
TI  - [Clinicopathological features of 8 patients with metastatic gastric tumors].
AB  - We examined the clinicopathological features of metastatic gastric tumor, using 9
      tumors of 8 patients. Histological diagnosis with all biopsy specimens were
      adenocarcinoma. Most of the metastatic sites were located in the middle or upper
      gastric corpus. Endoscopic features of the lesion showed a submucosal tumor-like
      (5 cases) and primary gastric cancer-like (3 cases) appearance.
      Immunohistochemical staining of cytokeratins, TTF-1, surfactant protein, ER, or
      MGB1 identified the primary site; 6 in the lung and 2 in the breast. One case was
      diagnosed based on the EGFR mutation analysis. In conclusion, immunohistochemical
      staining and molecular method are useful tools to distinguish metastatic gastric
      tumor from primary gastric cancer.

PMID- 22481260
TI  - [A case of Cowden disease with a germline mutation in exon5 of PTEN gene
      diagnosed based on typical esophageal multiple polypoid lesions observed on a
      medical checkup].
AB  - A man in his fifties had a medical checkup. Mucosal papillomatosis in his oral
      cavity and palmoplantar keratosis were observed. Esophagogastroduodenoscopy
      revealed multiple polypoid lesions both in the esophagus and stomach. In
      addition, colonoscopy showed schwannoma in the rectum. He underwent an operation
      for adenomatous goiter. At first his typical esophageal multiple polypoid lesion
      was a diagnostic cue to Cowden disease (CD). Other clinical findings convinced us
      that he was suffering from CD. He was, then, diagnosed as CD according to the
      criteria of International Cowden Consortium although he had no family medical
      history suspicious of CD. Interestingly, genetic testing revealed that the
      patient had a germline mutation in exon5 of PTEN on chromosome 10. It was a point
      mutation of C to T transition at codon130, resulting in nonsense mutation (CGA
      >TGA). A close follow-up, especially cancer surveillance, is necessary for him
      since CD is associated with a high risk of developing malignant disease. It is
      noted that the typical esophageal features can be a diagnostic cue to CD, as
      shown in the present case.

PMID- 22481261
TI  - [Gastric outlet obstruction caused by gastrostomy tube balloon in 3 cases].
AB  - We report 3 cases with unusual complications of gastric outlet obstruction caused
      by a gastrostomy tube balloon. All cases developed vomiting, and 2 cases were
      accompanied by hematemesis. Gastric ulcer was observed in 1 case, aspiration
      pneumonia was observed in 2 cases, and pancreatitis was observed in 1 case. This
      condition improved rapidly by correction of the position of the balloon in all
      cases. In patient vomiting during management for gastrostomy we need to consider
      migration of the gastrostomy tube balloon. Careful management of the gastrostomy
      tube balloon is important.

PMID- 22481262
TI  - [Successful management of liver metastasis from gastric adenosquamous carcinoma
      with adjuvant chemotherapy and radiofrequency ablation].
AB  - A 70-year-old man was given a diagnosis of advanced type 3 gastric cancer and
      underwent surgery. In addition to total gastrectomy and D2 lymph node resection,
      partial liver resection was performed due to detection of a solitary liver
      metastasis which was initially overlooked on preoperative CT.
      Histopathologically, the tumor was diagnosed as gastric adenosquamous carcinoma
      (Int, INFbeta, pT2 (ss), H1, ly1, v2 (mp), EVG, n (-), pPM (-), pDM (-)). Three
      metastasic lesions appeared in the liver on abdominal CT scan performed 3 months
      after the operation. The patient underwent adjuvant chemotherapy with S-1. Since
      enlargement of the liver metastases was observed following 2 courses of
      treatment, the patient received combination chemotherapy of irinotecan and
      cisplatin. Of 3 metastatic lesions, 1 disappeared and 2 decreased to less than 2
      cm in diameter after 8 courses of 2nd line treatment. Radiofrequency ablation
      (RFA) was successfully performed to treat the remaining liver metastases. The
      patient has been free of recurrence for 41 months.

PMID- 22481263
TI  - [Computed tomography colonography for 5 cases of pneumatosis cystoides
      intestinalis].
AB  - Computed tomography colonography (CTC) was performed in 5 patients with
      pneumatosis cystoides intestinalis (PCI). The virtual colonoscopy view of CTC as
      well as total colonoscopy (TCS) findings showed polypoid lesions in the colon,
      and multiplanar reconstruction images of the colon revealed in the polypoid
      lesions of the colon. We confirmed the diagnosis of PCI in all cases. CTC also
      detected the PCI lesions in the subserosa of the colonic wall which were not
      detected by TCS. Accurate evaluation of the extent of PCI involvement was
      obtained by CT air-contrast enema images. CTC is useful for detection of PCI
      lesions, assessment of the exact site and final diagnosis for PCI.

PMID- 22481264
TI  - [A case of hepatitis E differentially diagnosed from drug-induced liver injury].
AB  - A woman in her seventies was admitted because of general fatigue and liver
      dysfunction (ALT 2565 IU/l). She was diabetic and, 2 months ago, began eating
      kikuimo (Jerusalem artichoke) containing inulin, which is thought to decrease
      blood sugar level. Although tests showed no evidence of acute infection of HAV,
      HBV, HCV, EBV and CMV, a drug-induced lymphocyte stimulation test using kikuimo
      extract was positive. She was first diagnosed with drug-induced liver injury
      according to the Japanese diagnostic criteria for the disease. After a non
      eventful recovery, her serum was found to be positive for hepatitis E-antibody
      and RNA (genotype 3), indicating recent, autochthonous infection of HEV. The
      patient might have been misdiagnosed with drug-induced liver injury unless the
      serum test for HEV had been performed. We believe that HEV screening is mandatory
      for accurate diagnosis of hepatitis E and drug-induced liver injury.

PMID- 22481265
TI  - [A case of alcoholic hepatitis diagnosed by a liver biopsy and successfully
      treated by corticosteroid therapy].
AB  - A 50-year-old man with a history of alcohol intake exceeding 80 g/day was
      admitted because of severe liver dysfunction and high fever. A rapid increase of
      transaminase with remittent high fever was observed several days after admission.
      Abdominal CT scan demonstrated a 22*20 mm mass in segment 8, highly suggestive of
      hepatocellular carcinoma. However, because the etiology of the liver dysfunction
      was still unknown, we performed a liver biopsy on the sixth day. Histological
      examination of the liver specimen showed marked granulocyte infiltration, Mallory
      bodies, and hepatocyte ballooning, all consistent with alcoholic hepatitis. We
      made a final diagnosis of alcoholic hepatitis and successfully treated him with
      corticosteroids. This case suggests that a liver biopsy has diagnostic value in
      alcoholic hepatitis, especially in cases in which the diagnosis is uncertain.

PMID- 22481266
TI  - [A case of mediastinal pancreatic pseudocyst accompanied by pancreatic pleural
      effusion].
AB  - A 62-year-old man was admitted with dyspnea. Computed tomography (CT) revealed
      left massive pleural effusion and a cystic lesion in the posterior mediastinal
      compartment extending to the pancreatic head via the esophageal hiatus. The
      pleural effusion had a high amylase content. Based on these findings, we
      diagnosed mediastinal pancreatic pseudocyst accompanied by pancreatic pleural
      effusion. We treated him with CT-guided puncture and endoscopic pancreatic
      drainage. Endoscopic pancreatic treatment is possible for pancreatic pseudocysts.

PMID- 22481267
TI  - Osteochondritis dissecans development after bone contusion of the knee in the
      skeletally immature: a case series.
AB  - Osteochondritis dissecans (OCD) is thought to be an acquired osteochondral
      disorder, and its aetiology may be multifactorial. Trauma, both acute and
      repetitive events, has previously been proposed as a potential cause for OCD
      development. We present two cases of skeletally immature boys who developed a
      symptomatic OCD lesion following a femoral condyle bone contusion. These cases
      suggest that an acute traumatic event may lead to the development of OCD of the
      knee.

PMID- 22481268
TI  - Nonproteolytic properties of murine alternatively spliced tissue factor:
      implications for integrin-mediated signaling in murine models.
AB  - This study was performed to determine whether murine alternatively spliced tissue
      factor (masTF) acts analogously to human alternatively spliced tissue factor
      (hasTF) in promoting neovascularization via integrin ligation.
      Immunohistochemical evaluation of a spontaneous murine pancreatic ductal
      adenocarcinoma model revealed increased levels of masTF and murine full-length
      tissue factor (mflTF) in tumor lesions compared with benign pancreas;
      furthermore, masTF colocalized with mflTF in spontaneous aortic plaques of Ldlr(
      /-) mice, indicating that masTF is likely involved in atherogenesis and
      tumorigenesis. Recombinant masTF was used to perform in vitro and ex vivo studies
      examining its integrin-mediated biologic activity. Murine endothelial cells (ECs)
      rapidly adhered to masTF in a beta3-dependent fashion. Using adult and embryonic
      murine ECs, masTF potentiated cell migration in transwell assays. Scratch assays
      were performed using murine and primary human ECs; the effects of masTF and hasTF
      were comparable in murine ECs, but in human ECs, the effects of hasTF were more
      pronounced. In aortic sprouting assays, the potency of masTF-triggered vessel
      growth was undistinguishable from that observed with hasTF. The proangiogenic
      effects of masTF were found to be Ccl2-mediated, yet independent of vascular
      endothelial growth factor. In murine ECs, masTF and hasTF upregulated genes
      involved in inflammatory responses; murine and human ECs stimulated with masTF
      and hasTF exhibited increased interaction with murine monocytic cells under
      orbital shear. We propose that masTF is a functional homolog of hasTF, exerting
      some of its key effects via beta3 integrins. Our findings have implications for
      the development of murine models to examine the interplay between blood
      coagulation, atherosclerosis and cancer.

PMID- 22481269
TI  - Poly (ADP-ribose) transferase/polymerase-1-deficient mice resistant to age
      dependent decrease in beta-cell proliferation.
AB  - Basal and adaptive beta-cell regeneration capacity declines with old age, but the
      underlying molecular mechanisms remain incompletely understood. Poly (adenosine
      diphosphate [ADP]-ribose) polymerase 1 (PARP-1) is considered a multifunctional
      enzyme and transcription factor that regulates pancreatic beta-cell death,
      regeneration and insulin secretion. We analyzed the capacity of beta-cell
      regeneration in 2-month-old (young) and 12-month-old (old) wild-type (WT) and
      PARP-1-/- mice before and after low-dose streptozotocin (STZ), a stimulus of beta
      cell regeneration and the underlying mechanism. Before STZ administration, young
      WT and PARP-1-/- mice showed similar beta-cell proliferation. By contrast, old WT
      but not old PARP-1-/- mice showed severely restricted beta-cell proliferation. In
      further assessment of the adaptive beta-cell regeneration capacity with age, we
      observed that with a single low dose of STZ, young WT and PARP-1-/- mice showed a
      similar increase in beta-cell proliferation, with few changes in old WT mice.
      Surprisingly, adaptive beta-cell proliferation capacity was significantly higher
      in old PARP-1-/- mice than old WT mice after STZ administration. The ability of
      beta-cell mass to expand was associated with increased levels of the regenerating
      (Reg) genes RegI and RegII but not RegIV. Therefore, PARP-1 is a key regulator in
      beta-cell regeneration with advancing age in mice.

PMID- 22481270
TI  - Intravenous mesenchymal stem cells improve survival and motor function in
      experimental amyotrophic lateral sclerosis.
AB  - Despite some advances in the understanding of amyotrophic lateral sclerosis (ALS)
      pathogenesis, significant achievements in treating this disease are still
      lacking. Mesenchymal stromal (stem) cells (MSCs) have been shown to be effective
      in several models of neurological disease. To determine the effects of the
      intravenous injection of MSCs in an ALS mouse model during the symptomatic stage
      of disease, MSCs (1 * 106) were intravenously injected in mice expressing human
      superoxide dismutase 1 (SOD1) carrying the G93A mutation (SOD1/G93A) presenting
      with experimental ALS. Survival, motor abilities, histology, oxidative stress
      markers and [3H]D-aspartate release in the spinal cord were investigated. MSC
      injection in SOD1/G93A mice improved survival and motor functions compared with
      saline-injected controls. Injected MSCs scantly home to the central nervous
      system and poorly engraft. We observed a reduced accumulation of ubiquitin
      agglomerates and of activated astrocytes and microglia in the spinal cord of MSC
      treated SOD1/G93A mice, with no changes in the number of choline
      acetyltransferase- and glutamate transporter type 1-positive cells. MSC
      administration turned around the upregulation of metallothionein mRNA expression
      and of the activity of the antioxidant enzyme glutathione S-transferase, both
      associated with disease progression. Last, we observed that MSCs reverted both
      spontaneous and stimulus-evoked neuronal release of [3H]D-aspartate, a marker of
      endogenous glutamate, which is upregulated in SOD1/G93A mice. These findings
      suggest that intravenous administration of MSCs significantly improves the
      clinical outcome and pathological scores of mutant SOD1/G93A mice, thus providing
      the rationale for their exploitation for the treatment of ALS.

PMID- 22481271
TI  - The infective polymerization of conformationally unstable antithrombin mutants
      may play a role in the clinical severity of antithrombin deficiency.
AB  - Mutations affecting mobile domains of antithrombin induce conformational
      instability resulting in protein polymerization that associates with a severe
      clinical phenotype, probably by an unknown gain of function. By homology with
      other conformational diseases, we speculated that these variants might infect
      wild-type (WT) monomers reducing the anticoagulant capacity. Infective
      polymerization of WT polymers and different P1 mutants (p.R425del, p.R425C and
      p.R425H) were evaluated by using native gels and radiolabeled WT monomers and
      functional assays. Human embryonic kidney cells expressing the Epstein-Barr
      nuclear antigen 1 (HEK-EBNA) cells expressing inducible (p.R425del) or two novel
      constitutive (p.F271S and p.M370T) conformational variants were used to evaluate
      intracellular and secreted antithrombin under mild stress (pH 6.5 and 39 degrees
      C for 5 h). We demonstrated the conformational sensitivity of antithrombin London
      (p.R425del) to form polymers under mild heating. Under these conditions purified
      antithrombin London recruited WT monomers into growing polymers, reducing the
      anticoagulant activity. This process was also observed in the plasma of patients
      with p.R425del, p.R425C and p.R425H mutations. Under moderate stress,
      coexpression of WT and conformational variants in HEK-EBNA cells increased the
      intracellular retention of antithrombin and the formation of disulfide-linked
      polymers, which correlated with impaired secretion and reduction of anticoagulant
      activity in the medium. Therefore, mutations inducing conformational instability
      in antithrombin allow its polymerization with the subsequent loss of function,
      which under stress could sequestrate WT monomers, resulting in a new
      prothrombotic gain of function, particularly relevant for intracellular
      antithrombin. The in vitro results suggest a temporal and severe plasma
      antithrombin deficiency that may contribute to the development of the thrombotic
      event and to the clinical severity of these mutations.

PMID- 22481272
TI  - Different partners, opposite outcomes: a new perspective of the immunobiology of
      indoleamine 2,3-dioxygenase.
AB  - Indoleamine 2,3-dioxygenase (IDO), a metabolic enzyme that catalyzes tryptophan
      conversion into kynurenines, is a crucial regulator of immunity. Altered IDO
      activity is often associated with pathology, including neoplasia and
      autoimmunity. IDO is highly expressed in dendritic cells (DCs) that exploit the
      enzyme's activity and the production of tryptophan catabolites to regulate immune
      responses by acting on several cell types, including T lymphocytes, of which they
      promote a regulatory phenotype. IDO also contains immunoreceptor tyrosine-based
      inhibitory motifs (ITIMs) that, once bound by distinct molecular partners, will
      either promote degradation or initiate signaling activity and self-maintenance of
      the enzyme. We here discuss how ITIM-dependent molecular events can affect the
      functional plasticity of IDO by modifying the protein half-life and its enzymic
      and nonenzymic functions.

PMID- 22481274
TI  - Changing mother's hygiene and sanitation practices in resource constrained
      communities: case study of Turkana District, Kenya.
AB  - Lack of adequate sanitation, hygiene and safe portable water are serious global
      health problems that contribute to deaths of many children under the age of 5
      years annually, mainly due to diarrhoeal diseases. This study was set out to
      determine the extent to which sanitation and hygiene promotion influenced
      mothers' and children's health in Turkana District; one of the arid Northern
      frontier Districts of Kenya. A repeat cross-sectional study design with multi
      stage sampling method was used. A total of 300 mothers were randomly sampled for
      interviews in a baseline survey carried out in 2007 and in a post-intervention
      survey carried out in 2008. Data were collected using questionnaires and analyzed
      using SPSS for frequencies, cross tabulations and regression amongst other tests.
      Significant improvements were observed in hand washing practice, presence of hand
      washing soap at household and refuse pit ownership. In Kakuma Division the
      proportion of those who washed hands regularly increased from 48.8 to 91.3 %
      (chi(2) = 7.28, P = 0.122), in Lodwar Central, those who wash hands regularly
      increased from 85.5 to 89.9 % (chi2 = 10.85, P = 0.028) while in Lokichogio, the
      proportions increased from 77.5 to 93.8 % (chi2 = 15.56, P = 0.004). For hand
      washing soap at household, there was an increase in proportion of those who wash
      hands with soap from 65 to 78 % (chi2 = 3.87, P = 0.049) within the group with no
      formal education. There was significant reduction of diarrhoea prevalence in
      children aged less than 5 years. Sanitation and hygiene promotion based on
      community participatory approaches can lead to significant reduction of diarrhoea
      in children.

PMID- 22481275
TI  - Shape-controlled synthesis of high tap density cathode oxides for lithium ion
      batteries.
AB  - A new synthesis approach has been developed to control the morphology of Mn- and
      Ni-containing carbonate precursors. Through a controlled release of the
      precipitate, the carbonate precursors form in a "non-classical crystallization"
      process similar to the natural crystallization of CaCO3, resulting in shapes
      tunable from microcubes to microspheres. The oriented attachment in the
      mesocrystal precursors leads to uniform particles with high tap density. Further
      lithiation of the shape-controlled carbonates produces the final 5 V spinel
      cathode LiMn1.5Ni0.5O4 with superior electrochemical properties in lithium-ion
      cells, while maintaining the high tap density and offering high volumetric energy
      density. 

PMID- 22481273
TI  - Labor migration and HIV risk: a systematic review of the literature.
AB  - To inform the development of multilevel strategies for addressing HIV risk among
      labor migrants, 97 articles from the health and social science literatures were
      systematically reviewed. The study locations were Africa (23 %), the Americas (26
      %), Europe (7 %), South East Asia (21 %), and Western Pacific (24 %). Among the
      studies meeting inclusion criteria, HIV risk was associated with multilevel
      determinants at the levels of policy, sociocultural context, health and mental
      health, and sexual practices. The policy determinants most often associated with
      HIV risk were: prolonged and/or frequent absence, financial status, and difficult
      working and housing conditions. The sociocultural context determinants most often
      associated with HIV risk were: cultural norms, family separation, and low social
      support. The health and mental health factors most often associated with HIV risk
      were: substance use, other STIs, mental health problems, no HIV testing, and
      needle use. The sexual practices most often associated with increased HIV risk
      were: limited condom use, multiple partnering, clients of sex workers, low HIV
      knowledge, and low perceived HIV risk. Magnitude of effects through multivariate
      statistics were demonstrated more for health and mental health and sexual
      practices, than for policy or sociocultural context. The consistency of these
      findings across multiple diverse global labor migration sites underlines the need
      for multilevel intervention strategies. However, to better inform the
      development, implementation, and evaluation of multilevel interventions,
      additional research is needed that overcomes prior methodological limitations and
      focuses on building new contextually tailored interventions and policies.

PMID- 22481276
TI  - Do survival rate and serum ion concentrations 10 years after metal-on-metal hip
      resurfacing provide evidence for continued use?
AB  - BACKGROUND: Owing to concerns attributable to problems associated with metal-on
      metal bearing surfaces, current evidence for the use of hip resurfacing is
      unclear. Survival rates reported from registries and individual studies are
      controversial and the limited long-term studies do not conclusively allow one to
      judge whether hip resurfacing is still a reasonable alternative to conventional
      THA. QUESTIONS/PURPOSES: We asked whether the long-term survival rate of hip
      resurfacing is comparable to that of conventional THA and certain factors can be
      identified that influence serum ion concentration 10 years postoperatively. We
      specifically assessed (1) the 10-year survivorship in the whole cohort and in
      male and female patients, (2) serum concentrations of metal ions in patients with
      hip resurfacing who had not undergone revision surgery, and (3) potential
      influencing factors on the serum ion concentration. METHODS: We retrospectively
      reviewed our first 95 patients who had 100 hip resurfacings performed from 1998
      to 2001. The median age of the patients at surgery was 52 years (range, 28-69
      years); 49% were men. We assessed the survival rate (revision for any reason as
      the end point), radiographic changes, and serum ion concentrations for cobalt,
      chromium, and molybdenum. The correlations between serum ion concentration and
      patient-related factors (age, sex, BMI, activity) and implant-related factors
      (implant size, cup inclination, stem-shaft angle) were investigated. The minimum
      followup was 9.3 years (mean, 10 years; range, 9.3-10.5 years). RESULTS: The 10
      year survivorship was 88% for the total cohort. The overall survival rate was
      greater in men (93%) than in women (84%). Median serum ion levels were 1.9 MUg/L
      for chromium, 1.3 MUg/L for cobalt, and 1.6 MUg/L for molybdenum. Radiolucent
      lines around acetabular implants were observed in 4% and femoral neck thinning in
      5%. CONCLUSIONS: Although our overall failure rate was greater than anticipated,
      the relatively low serum ion levels and no revisions for pseudotumors in young
      male patients up to 10 years postoperatively provide some evidence of the
      suitability of hip resurfacing in this subgroup. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See the Instructions for Authors for a complete description of
      levels of evidence.

PMID- 22481277
TI  - Biographical sketch: George E. Bennett, MD (1885-1962).
AB  - This biographical sketch on George Bennett corresponds to the historic text, The
      Classic: Shoulder and Elbow Lesions Distinctive of Baseball Players (1947),
      available at DOI 10.1007/s11999-012-2335-2 .

PMID- 22481278
TI  - Fish stranding in freshwater systems: sources, consequences, and mitigation.
AB  - Fish can become stranded when water levels decrease, often rapidly, as a result
      of anthropogenic (e.g., canal drawdown, hydropeaking, vessel wakes) and natural
      (e.g., floods, drought, winter ice dynamics) events. We summarize existing
      research on stranding of fish in freshwater, discuss the sources, consequences,
      and mitigation options for stranding, and report current knowledge gaps. Our
      literature review revealed that ~65.5% of relevant peer-reviewed articles were
      found to focus on stranding associated with hydropower operations and irrigation
      projects. In fact, anthropogenic sources of fish stranding represented 81.8% of
      available literature compared to only 19.9% attributed to natural fish stranding
      events. While fish mortality as a result of stranding is well documented, our
      analysis revealed that little is known about the sublethal and long-term
      consequences of stranding on growth and population dynamics. Furthermore, the
      contribution of stranding to annual mortality rates is poorly understood as are
      the potential ecosystem-scale impacts. Mitigation strategies available to deal
      with stranding include fish salvage, ramping rate limitations, and physical
      habitat works (e.g., to contour substrate to minimize stranding). However, a
      greater knowledge of the factors that cause fish stranding would promote the
      development and refinement of mitigation strategies that are economically and
      ecologically sustainable.

PMID- 22481279
TI  - Community engagement in the management of biosolids: lessons from four New
      Zealand studies.
AB  - Biosolids management has been largely overlooked as an issue for environmental co
      management, collaborative learning and public participation. This paper
      summarises four research projects on facilitating community involvement in
      biosolids management in New Zealand. The authors situate these studies both in
      relation to the New Zealand institutional and policy context for the management
      of biosolids and in relation to the themes of public participation and social
      learning in the literature on community involvement in environmental management.
      From the studies it can be concluded that: the incorporation of the knowledge and
      views of Maori is important from both public-participation and social-learning
      perspectives; both public-participation and social-learning approaches must
      consider the role of issue-definition in relation to willingness to participate;
      democratic accountability remains a challenge for both approaches; and locating
      biosolids management within an integrated water-and-wastewater or sustainable
      waste-management strategy may facilitate wider community participation as well as
      better-coordinated decision-making.

PMID- 22481280
TI  - Association between IgG4-related disease and progressively transformed germinal
      centers of lymph nodes.
AB  - Progressively transformed germinal centers is a benign condition of unknown
      pathogenesis characterized by a distinctive variant form of reactive follicular
      hyperplasia in lymph nodes. We recently reported Ig G4-related disease in
      progressively transformed germinal centers. However, no large case series has
      been reported and clinicopathologic findings remain unclear. Here, we report 40
      Japanese patients (28 men, 12 women; median age, 56 years) with progressively
      transformed germinal centers of the lymph nodes who fulfilled the histological
      diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed
      germinal centers), with asymptomatic localized lymphadenopathy involving the
      submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes
      only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31
      examined patients had allergic disease. Histologically, the lymph nodes
      demonstrated uniform histological findings, namely marked follicular hyperplasia
      with progressively transformed germinal centers, and localization of the majority
      of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and
      peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined
      patients, respectively. Eighteen patients subsequently developed extranodal
      lesions (including five who developed systemic disease), which on histological
      examination were consistent with IgG4-related disease. IgG4(+) progressively
      transformed germinal centers presents with uniform clinicopathological features
      of asymptomatic localized submandibular lymphadenopathy, which persists and/or
      relapses, and sometimes progresses to extranodal lesions or systemic disease.
      Nine patients were administered steroid therapy when the lesions progressed, to
      which all responded well. We suggest that IgG4(+) progressively transformed
      germinal centers should be included in the IgG4-related disease spectrum.

PMID- 22481281
TI  - Clinicopathologic and molecular features of sporadic early-onset colorectal
      adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation,
      rectal and sigmoid involvement, and adverse morphologic features.
AB  - Recent literature suggests an increasing incidence of colorectal carcinoma in
      young patients. We performed a histologic, molecular, and immunophenotypic
      analysis of patients with sporadic early-onset (<=40 years of age) colorectal
      carcinoma seen at our institution from the years 2000-2010 and compared these
      tumors to a cohort of consecutively resected colorectal carcinomas seen in
      patients >40 years of age. A total of 1160 primary colorectal adenocarcinomas
      were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were
      diagnoses in patients <=40 years of age of which 13 (17%) demonstrated
      abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline
      genetic disorders (two patients with familial adenomatous polyposis, one patient
      with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three
      patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic
      early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160,
      5%) and were compared with a control group comprising 73 consecutively resected
      colorectal carcinomas with proficient DNA mismatch repair in patients >40 years
      of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%)
      were diagnosed between the age of 35 and 40 years of age. Compared with the
      control group, the early-onset colorectal carcinoma group was significantly
      different with respect to tumor location (P<0.007) with 80% (44/55 cases)
      identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%).
      Morphologically, early-onset colorectal carcinomas more frequently displayed
      adverse histologic features compared with the control colorectal carcinoma group
      such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P=0.021),
      perineural invasion (16/55, 29% vs 8/73, 11%, P=0.009) and venous invasion
      (12/55, 22% vs 4/73, 6%, P=0.006). A precursor adenomatous lesion was less
      frequently identified in the early-onset colorectal carcinoma group compared with
      the control group (19/55, 35% vs 39/73, 53%, P=0.034). Of the early-onset
      colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared
      with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS
      mutations, although this difference did not reach statistical significance
      (P=0.13). BRAF V600E mutations were not identified in the early-onset colorectal
      carcinoma group. No difference was identified between the two groups with regard
      to tumor stage, tumor size, number of lymph node metastases, lymphatic invasion,
      tumor budding, mucinous histology, or tumor-infiltrating lymphocytes. Both groups
      had similar recurrence-free (P=0.28) and overall survival (P=0.73). However,
      patients in the early-onset colorectal carcinoma group more frequently either
      presented with or developed metastatic disease during their disease course
      compared with the control colorectal carcinoma group (25/55, 45% vs 18/73, 25%,
      P=0.014). In addition, 8/55 patients (15%) in the early-onset colorectal
      carcinoma group developed local recurrence of their tumor while no patients in
      the control colorectal carcinoma group developed local recurrence (P<0.001),
      likely due to the increased incidence of rectal carcinoma in the patients with
      early-onset colorectal carcinoma. Our study demonstrates that colorectal
      carcinoma is not infrequently diagnosed in patients <=40 years of age and is not
      frequently the result of underlying Lynch syndrome or associated with other
      cancer-predisposing genetic conditions or chronic inflammatory conditions. These
      tumors have a striking predilection for the distal colon, particularly the
      sigmoid colon and rectum and are much more likely to demonstrate adverse
      histologic factors, including signet ring cell differentiation, venous invasion,
      and perineural invasion.

PMID- 22481282
TI  - Intra-tumoral budding in preoperative biopsy specimens predicts lymph node and
      distant metastasis in patients with colorectal cancer.
AB  - Tumor budding, a histological hallmark of epithelial-mesenchymal transition in
      colorectal cancer, is a parameter of tumor progression and according to the
      International Union Against Cancer/American Joint Committee on Cancer an
      'additional' prognostic factor. The current definition of tumor budding is
      reserved for the invasive tumor front of colorectal cancer (so called peri
      tumoral budding), but tumor buds can also be observed in small preoperative
      biopsy specimens. Whereas the prognostic value of peri-tumoral budding assessed
      in resection specimens has found wide acceptance, the value of budding in
      preoperative biopsies, which normally do not encompass the invasive tumor margin
      and hence can be called intra-tumoral budding, has not been systematically
      investigated yet. Therefore, the aim of this study is to assess the predictive
      value of intra-tumoral budding for lymph node and distant metastasis in
      preoperative biopsies. Preoperative biopsy samples and consecutive resection
      specimens from 72 patients with pathological information on TNM stage, vascular,
      lymphatic and perineural invasion, and tumor border configuration were used to
      evaluate intra-tumoral budding and peri-tumoral budding. Both parameters were
      scored semiquantitatively as 'high' (detectable at low power magnification * 2.5)
      and 'low' (occasional budding at intermediate magnification * 10, difficult to
      find or absent). In biopsy samples high intra-tumoral budding was observed in
      12/72 patients (17%) and associated with high peri-tumoral budding in the
      corresponding resection specimens (P=0.008). Additionally, there was a
      correlation between high intra-tumoral budding and lymph node metastasis
      (P=0.034), distant metastasis (P=0.007) and higher tumor grade (P=0.025). Peri
      tumoral budding was associated with higher N stage (P=0.004), vascular (P=0.046)
      and lymphatic invasion (P=0.019) as well as with an infiltrating tumor border
      (P<0.001), reflecting the predictive power of peri-tumoral budding for tumor
      progression. High intra-tumoral budding in preoperative biopsy samples of
      colorectal cancer patients predicts high peri-tumoral budding at the invasive
      margin and lymph node metastasis in the corresponding resection specimens as well
      as distant metastasis.

PMID- 22481283
TI  - The prognostic and predictive power of redox protein expression for anthracycline
      based chemotherapy response in locally advanced breast cancer.
AB  - Neoadjuvant chemotherapy has become the standard of care for locally advanced
      primary breast cancer. Anthracycline-based regimens have proven to be one of the
      most effective treatments in this setting. As certain cytotoxic antineoplastic
      agents, such as anthracyclines, generate reactive oxygen species as a by-product
      of their mechanism of action, we examined whether redox protein expression was
      involved in the response to anthracycline-based chemotherapy and with clinical
      outcome. Pre-treatment needle core biopsy and post-anthracycline treatment tumour
      sections were analysed from 98 cases. In all, 32 individuals had a complete
      clinical response and 17 had a complete pathological response.
      Immunohistochemical staining was performed for eight redox proteins: thioredoxin,
      thioredoxin reductase, thioredoxin interacting protein (TxNIP), glutathione S
      transferase (GST) pi, theta and alpha, catalase and manganese superoxide
      dismutase. GST pi (P=0.05) and catalase (P=0.045) were associated with
      pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and
      thioredoxin reductase (P=0.022) were independent prognostic factors for distant
      metastasis-free survival and TxNIP for overall survival (P=0.014). In oestrogen
      receptor negative patients that are known to have a poor overall survival, a
      considerably worse prognosis was seen in cases that exhibited low expression of
      TxNIP (P=0.000003), stratifying patients into more defined groups. This study
      indicates the importance of redox regulation in determining breast cancer
      response to anthracycline-based chemotherapy and provides ways of further
      stratifying pre-chemotherapy patients to potentially allow more tailored
      treatments.

PMID- 22481284
TI  - Alcoholic chronic pancreatitis and alcoholic liver cirrhosis: differences in
      alcohol use habits and patterns in Indian subjects.
AB  - OBJECTIVES: Alcohol abuse is a risk factor for both liver cirrhosis and chronic
      pancreatitis. However, less than 15% of heavy drinkers develop these
      complications. Coexistence of cirrhosis and pancreatitis in the same patient is
      considered uncommon. We compared drinking patterns and related patient factors in
      patients with alcoholic liver cirrhosis and alcoholic chronic pancreatitis.
      METHODS: A prospective evaluation of 307 patients (all men: 188 with alcoholic
      liver cirrhosis and 119 with alcoholic chronic pancreatitis) was conducted over a
      7-year period using a detailed alcohol assessment proforma. Assessment of
      demographic features, diet, and other habits like tobacco smoking were recorded.
      RESULTS: Patients with alcoholic liver cirrhosis were older. The mean +/- SD age
      in alcoholic liver cirrhosis was 52.4 +/- 9.16 years and 47.1 +/- 9.78 years (P <
      0.001) in alcoholic chronic pancreatitis. The mean +/- SD age when they started
      drinking was similar in both groups (22.8 +/- 5.32 years and 24.3 +/- 6.94; P >
      0.05). The mean +/- SD duration of drinking was higher in the cirrhosis group
      (29.5 +/- 10.25 years) than in the pancreatitis group (21.5 +/- 9.61 years) (P <
      0.001). Fifty-nine percent of cirrhosis and 75% of pancreatitis were heavy
      tobacco smokers (P = 0.004). CONCLUSIONS: There are distinct differences in
      drinking patterns and related patient factors between alcoholic liver cirrhosis
      and alcoholic chronic pancreatitis, suggesting the need to orient different
      interventional strategies.

PMID- 22481285
TI  - The significance of the volume of pancreatic juice measured at secretin
      stimulation testing: a single-center evaluation of 224 classical secretin
      stimulation tests.
AB  - OBJECTIVES: (1) To quantitate volume production during secretin stimulation
      testing in patients suspected of having chronic pancreatitis (CP); (2) to compare
      volume production to clinical criteria for the diagnosis of CP. METHODS: A total
      of 224 patients referred for suspected CP were reviewed retrospectively for
      clinical information supporting the diagnosis of CP. The patients were divided
      into 2 groups: those with peak bicarbonate (PB) of less than 80 mEq/L and those
      with PB of 80 mEq/L or greater (ie, CP and no CP). For a separate comparison, the
      patients were also placed into similar 2 groups based on clinical criteria. The
      volume, total bicarbonate output, volume per kilogram, and PB of pancreatic juice
      after secretin stimulation in patients thought to have CP were compared to those
      thought not to have CP. RESULTS: Volume was lower in the patients with PB of less
      than 80 mEq/L (206 +/- 114 and 269 +/- 106 mL) and lower in patients who met
      clinical criteria for CP (203 +/- 109 and 271 +/- 108 mL), P < 0.001 for both,
      but there was significant overlap (volume alone did not accurately discriminate
      CP from no CP). CONCLUSIONS: During secretin stimulation testing, bicarbonate
      parameters likely are better predictors of CP than volume parameters. Changes in
      the production of the volume of pancreatic juice during secretin stimulation
      likely reflect relatively late changes in pancreatic function.

PMID- 22481286
TI  - Down-regulation of aquaporin 1 in rats with experimental acute necrotizing
      pancreatitis.
AB  - OBJECTIVES: The objectives of this study were to investigate the expression of
      aquaporin 1 in capillary endothelial cells of rats with experimental acute
      necrotizing pancreatitis (ANP) and to explore its pathogenic role in capillary
      leak. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into
      control (n = 32) and ANP groups (n = 32). Eight rats in each group were killed at
      3, 6, 12, and 18 hours after induction of experimental models. Quantity of
      ascites and levels of serum amylases were measured. Capillary permeability in
      pancreas, lung, and intestinal tissue was detected by Evans blue extravasation
      method. Aquaporin 1 expression in pancreas, lung, and intestinal tissue was
      detected by real-time polymerase chain reaction, immunohistochemical staining,
      and Western blot. RESULTS: Serum amylase level was significantly higher in ANP
      group than in controls (P < 0.05). Evans blue concentration in tissues in the ANP
      group was significantly higher than that in controls (P < 0.05). Aquaporin 1 mRNA
      and protein expressions in tissues were significantly less in the ANP group than
      in the controls (P < 0.05). CONCLUSIONS: The expression of aquaporin 1 was down
      regulated in the pancreas, lung, and intestinal tissue of ANP rats, which could
      play an important role in the pathogenesis of capillary leak syndrome.

PMID- 22481287
TI  - Effects of FTY720 and rapamycin on inflammation in taurocholate-induced acute
      pancreatitis in the rat.
AB  - OBJECTIVES: This study aimed at T-cell inhibition by immunosuppressants to reduce
      cell damage and improve the course of severe acute pancreatitis (SAP). METHODS: A
      taurocholate-induced SAP was used and 5 groups were compared: (1) rapamycin +
      FTY720, (2) rapamycin, (3) FTY720, (4) cortisol, and (5) control: sodium
      chloride. Drugs were applied intravenously at SAP induction; 6 hours later, rats
      were killed. Interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor alpha,
      platelet-activating factor, amylase, and lipase were measured in serum and
      myeloperoxidase tissue activity in pancreas, kidney, lung, liver, and spleen.
      Edema, inflammation, and necrosis were histologically determined in pancreas.
      CD4/CD8 immunohistochemistry was performed. RESULTS: Inflammation was ameliorated
      in all 4 treated groups. Necrosis development was suppressed by FTY720, FTY720 +
      rapamycin, and cortisol. IL-6 and IL-10 were significantly lower in these groups.
      Amylase was higher in all treatment groups compared to the controls except for
      the cortisol group. Tumor necrosis factor alpha, lipase, and myeloperoxidase
      activity were not affected by therapy. CD4+/CD8+ cells were significantly less in
      FTY720-treated pancreata. CONCLUSION: Rapamycin and FTY720 ameliorated the
      severity of SAP, which may be due to early suppression of helper T cells. FTY720
      reduced the development of pancreatic necrosis. The combination of both
      immunosuppressants did not show advantage to treatment with FTY720 alone.

PMID- 22481288
TI  - Glucagonlike peptide 2 protects intestinal barrier in severe acute pancreatitis
      through regulating intestinal epithelial cell proliferation and apoptosis.
AB  - OBJECTIVE: To investigate the protective effect of glucagon-like peptide 2 (GLP
      2) on intestinal barrier dysfunction in severe acute pancreatitis and to explore
      the putative mechanism of this effect. METHODS: Thirty rats were randomly divided
      into 3 groups. Group 1 received sham operation. Severe acute pancreatitis was
      induced in group 2 and group 3 via retrograde injection of 3% sodium taurocholate
      to the pancreatic duct. Rats in group 3 were peritoneally injected with GLP-2.
      Intestinal barrier dysfunction was characterized by the histological measurements
      and concentration of plasma diamine oxidase. The tissue sections of ileum were
      collected for the detection of proliferating cell nuclear antigen protein and
      apoptosis. RESULTS: Glucagon-like peptide 2 administration improved the ileal
      mucosal injury, which was also demonstrated by the histological score of ileal
      mucosa. The concentration of diamine oxidase was decreased in rats with acute
      pancreatitis treated with GLP-2. Acute pancreatitis-induced epithelial cell
      apoptosis was partly prevented by GLP-2. Immunohistochemical staining of
      proliferating cell nuclear antigen protein was increased in group 3 compared with
      that in group 2. CONCLUSIONS: Results from this study suggest that GLP-2 has a
      protective effect on intestinal barrier dysfunction in rats with severe acute
      pancreatitis via mechanisms closely involving promotion of cell growth and
      inhibition of intestinal epithelial cell apoptosis.

PMID- 22481289
TI  - Malignant transformation of branch duct-type intraductal papillary mucinous
      neoplasms of the pancreas based on contrast-enhanced endoscopic ultrasonography
      morphological changes: focus on malignant transformation of intraductal papillary
      mucinous neoplasm itself.
AB  - OBJECTIVES: The natural history of branch duct-type intraductal papillary
      mucinous neoplasms (BD-IPMNs) of the pancreas remains unclear. We conducted a
      retrospective long-term follow-up study for malignant transformation (MT) of BD
      IPMNs focusing on morphological changes. METHODS: The subjects consisted of 142
      patients who underwent contrast-enhanced endoscopic ultrasonography for initial
      diagnosis from January 2001 with more than 12 months of follow-up. The MT rate,
      including the co-occurrence of invasive ductal cancer, was evaluated by
      univariate and multivariate analysis. In addition, on the basis of morphological
      changes in patients who underwent surgery, the predictive factors for malignant
      IPMNs were evaluated. RESULTS: Median follow-up term was 42.5 months (range, 12
      105 months). Thirty patients who exhibited morphological changes underwent
      surgery. Malignant transformation occurred in 9 patients (6.3%), and 5-year MT
      rate was 10.7%. The co-occurrence of invasive ductal cancer was seen in 5
      patients. Multivariate analysis showed that the existence of mural nodules at
      initial diagnosis and involvement of main pancreatic duct were significant
      predictors of MT of BD-IPMN. CONCLUSIONS: Malignant transformation of BD-IPMN is
      not rare. The observation of morphological changes of main pancreatic duct and
      nodules, mainly on contrast-enhanced endoscopic ultrasonography, is practical and
      useful for predicting MT of BD-IPMN itself.

PMID- 22481290
TI  - Validity of the urinary trypsinogen-2 test in the diagnosis of acute
      pancreatitis.
AB  - OBJECTIVES: A simple urinary trypsinogen-2 test was evaluated for the diagnosis
      of acute pancreatitis. METHODS: This prospective multicenter study enrolled
      consecutive patients with acute abdominal pain who presented to the emergency
      department or who were hospitalized at 1 of 21 medical institutions in Japan.
      Patients were tested with urinary trypsinogen-2 dipstick test and a quantitative
      trypsinogen-2 assay, and these values were compared with serum amylase and lipase
      findings. RESULTS: A total of 412 patients were enrolled. The trypsinogen-2
      dipstick test was positive in 107 of 156 patients with acute pancreatitis
      (sensitivity, 68.6%) and in 33 of 256 patients with nonpancreatic abdominal pain
      (specificity, 87.1%). The sensitivity for the diagnosis of pancreatitis caused by
      alcohol and gallstones by the dipstick test was 72.2% and 81.8%, respectively,
      which was much higher than those associated with amylase testing. There are
      several degrees of positivity within the urinary trypsinogen-2 dipstick test.
      Modification of the cutoff point such that positive (+) and most positive (++)
      results were interpreted as a positive result, the specificity and positive
      likelihood ratio increased to 92.2% and 7.63, respectively. CONCLUSIONS: This
      simple, rapid, easy, and noninvasive urinary trypsinogen-2 test can diagnose or
      rule out most cases of acute pancreatitis.

PMID- 22481291
TI  - Clinically relevant pancreas-related infectious complication after
      pancreaticoenteral anastomosis could be predicted by the parameters obtained on
      postoperative day 3.
AB  - OBJECTIVES: Pancreatic fistula or pancreas-related infectious complications are
      one of the most common surgical complications after pancreatic surgery. The aims
      of this study were, first, to reveal the risk factors for clinically relevant
      pancreas-related infectious complications and, second, to identify those risk
      factors that are obtainable within the first 3 postoperative days. METHODS: One
      hundred seven consecutive patients who underwent pancreaticoenteral anastomosis
      between October 2007 and November 2010 were enrolled. RESULTS: There were 36
      patients with clinical pancreas-related infectious complications among 107 in
      this series of patients. Univariate and multivariate analyses revealed that a
      narrow main pancreatic duct diameter (<3 mm) was an independent risk factor for
      clinically relevant pancreas-related infectious complication. Univariate and
      multivariate analyses also revealed that a body temperature of 38 degrees C or
      higher on postoperative day 3 (POD3), a leukocyte count of 9.8 * 10(9)/L or
      greater on POD3, and a drain fluid amylase level of 3000 IU/L or higher on POD3
      were significant predictive factors for clinically relevant pancreas-related
      infectious complication for 58 patients with a narrow main pancreatic duct.
      CONCLUSIONS: In view of the clinical variables obtained on POD3, such as amylase
      levels in drain effluent, body temperature, and leukocyte count, clinically
      relevant pancreas-related infections could be predicted well.

PMID- 22481292
TI  - Incidence of hyperamylasemia after endoscopic ultrasound-guided fine needle
      aspiration of pancreatic lesions: a multicenter study from China.
AB  - OBJECTIVES: There have been few reports regarding the incidence of
      hyperamylasemia after endoscopic ultrasound-guided fine needle aspiration (EUS
      FNA). In particular, the potential risk factors involved in the development of
      hyperamylasemia have not been analyzed owing to the small number of cases
      reported. The aim of this study was to evaluate hyperamylasemia and associated
      risk factors after EUS-FNA of a large sample of pancreatic lesions. METHODS:
      Patients who underwent EUS-FNA for treatment of a pancreatic lesion were
      recruited from 6 medical centers in China. RESULTS: A total of 1023 patients
      presenting with pancreatic lesions between January 2004 and June 2008 were
      enrolled in this study, with 48 (4.7%) of the 1023 patients presenting with
      hyperamylasemia 3 hours after the procedure. These patients had a mean +/- SD
      serum amylase level of 331.64 +/- 138.60 UI/L. With the use of unconditional
      logistic regression analysis, the incidence of hyperamylasemia was found to be
      affected by the type of cystic lesion present and the gauge of the needle used.
      In 4 (0.4%) of the 1023 patients, acute pancreatitis developed. CONCLUSIONS: The
      overall incidence of hyperamylasemia after EUS-FNA is relatively low. However,
      the type of cystic lesion present and the gauge of the needle (19G) used for EUS
      FNA may represent risk factors for the incidence of hyperamylasemia.

PMID- 22481293
TI  - Pancreatic exocrine function and morphology following an episode of acute
      pancreatitis.
AB  - OBJECTIVE: The objective of this study was to assess pancreatic exocrine function
      (PEF) and morphology in patients recovering from a first episode of acute
      pancreatitis (AP). METHODS: Sixty-five eligible patients recovering from AP and
      70 healthy volunteers were enrolled in this study. We evaluated PEF by fecal
      elastase 1 (FE-1) and used ultrasonography to detect pancreatic morphology for
      all patients and 40 controls. RESULTS: Exocrine pancreatic insufficiency (EPI)
      incidence in the severe and mild AP subgroups was 60.5% and 39.5%, respectively.
      The FE-1 level in patients who had undergone surgical care was significantly
      lower compared with the controls (P < 0.01), whereas no difference was observed
      between the alcoholic and nonalcoholic groups (P > 0.05). Surprisingly, the
      defecation change correlated with the EPI level. In these patients, a stepwise
      recovery was observed over the following 2.4 years. Compared with the controls,
      the diameter of pancreatic duct was enlarged, and abdominal pain during recovery
      was found to be the independent risk factor for pancreatic duct expansion,
      although a significant difference was not exhibited between the AP subgroups
      concerning FE-1 concentration (P = 0.591). CONCLUSIONS: Our results indicated
      that many AP patients may have long-lasting EPI and an expanded main pancreatic
      duct; thus, routine evaluation of PEF is warranted.

PMID- 22481294
TI  - Prospective comparison of scar-related satisfaction and quality of life after
      laparoscopic versus open radical prostatectomy: no differences from patients'
      point of view.
AB  - OBJECTIVES: To evaluate and compare scar-related satisfaction in patients treated
      with open (ORP) versus laparoscopic radical prostatectomy (LRP). PATIENTS AND
      METHOD: We prospectively included all patients treated with ORP and LRP in our
      department between March and June 2010. Scar-related outcomes were collected at 1
      and 3 months postoperatively. Three months after surgery, all patients filled up
      a questionnaire concerning their scar-related symptoms, scar self-consciousness
      and satisfaction. These variables were statistically compared between the two
      groups. RESULTS: A total of 101 patients were included for analysis. Of them, 48,
      49 and 4 were treated with LRP, ORP and LRP converted to ORP, respectively. Age
      distribution was not statistically different between groups. Postoperatively, 5
      patients experienced skin infection on their scar site, 2 in the ORP and 3 in the
      LRP group. The most frequently reported symptom was scar itching, that was more
      frequent after LRP, although difference was not significant (33 vs. 19%, p =
      0.2). According to patient scar-related consciousness, satisfaction and impact on
      quality of life, no differences were reported between groups. Impact on quality
      of life was insignificant in 27 (55%) versus 21 (44%) patients after ORP and LRP,
      respectively (p = 0.3). CONCLUSION: With an overall low impact on satisfaction
      and quality of life, scars gendered by LRP and ORP were not different from
      patients' point of view. In patients undergoing radical prostatectomy, the
      cosmetic aspect of scars does not seem to be a concern.

PMID- 22481295
TI  - Magnetotransport properties of a magnetically modulated two-dimensional electron
      gas with the spin-orbit interaction.
AB  - We study the electrical transport properties of a two-dimensional electron gas
      (2DEG) with the Rashba spin-orbit interaction in the presence of a constant
      perpendicular magnetic field (B(0)( z) which is weakly modulated by B1 = B1
      cos(qx) z, where B(1) ? B(0) and q = 2pi/a with a the modulation period. We
      obtain the analytical expressions of the diffusive conductivities for spin-up and
      spin-down electrons. The conductivities for spin-up and spin-down electrons
      oscillate with different frequencies and produce beating patterns in the
      amplitude of the Weiss and Shubnikov-de Haas oscillations. We show that the
      Rashba strength can be determined by analyzing the beating pattern in the Weiss
      oscillation. We find a simple equation which determines the Rashba spin-orbit
      interaction strength if the number of Weiss oscillations between any two
      successive nodes is known from the experiment. We compare our results with the
      electrically modulated 2DEG with the Rashba interaction. For completeness, we
      also study the beating pattern formation in the collisional and the Hall
      conductivities.

PMID- 22481296
TI  - Synthetic antibodies as tools to probe RNA-binding protein function.
AB  - RNA-binding proteins (RBPs) have essential roles in post-transcriptional
      regulation of gene expression. They bind sequence elements in specific mRNAs and
      control their splicing, transport, localization, translation, and stability. A
      complete understanding of RBP function requires identification of the target RNAs
      that an RBP regulates, the mechanisms by which the RBP regulates these targets,
      and the biological consequences for the cell in which these transactions occur.
      Antibodies are key tools in such studies: first, mRNA targets of RBPs can be
      identified by co-immunoprecipitation of RBPs with their associated RNAs followed
      by microarray analysis or sequencing; second, partner proteins can be identified
      by immunoprecipitation of the RBP followed by mass spectrometry; third, the
      mechanisms and functions of RBPs can be inferred from loss-of-function studies
      employing antibodies that block RBP-RNA interactions. One potentially powerful
      approach to making antibodies for such studies is the generation of synthetic
      antibodies using phage display, which involves in vitro selection using a human
      designed antibody library to generate antibodies that recognize a target protein.
      Using two well-characterized Drosophila RNA-binding proteins, Staufen and Smaug,
      for proof-of-principle, we demonstrate that synthetic antibodies can be generated
      and used either to perform RNA-coimmunoprecipitations (RIPs) to identify RBP
      bound mRNAs, or to block RBP-RNA interactions. Given that synthetic antibody
      selection protocols are amenable to high-throughput antibody production, these
      results demonstrate that synthetic antibodies can be powerful tools for genome
      wide studies of RBP function.

PMID- 22481297
TI  - A conceptual framework and principles for trusted pervasive health.
AB  - BACKGROUND: Ubiquitous computing technology, sensor networks, wireless
      communication and the latest developments of the Internet have enabled the rise
      of a new concept-pervasive health-which takes place in an open, unsecure, and
      highly dynamic environment (ie, in the information space). To be successful,
      pervasive health requires implementable principles for privacy and
      trustworthiness. OBJECTIVE: This research has two interconnected objectives. The
      first is to define pervasive health as a system and to understand its trust and
      privacy challenges. The second goal is to build a conceptual model for pervasive
      health and use it to develop principles and policies which can make pervasive
      health trustworthy. METHODS: In this study, a five-step system analysis method is
      used. Pervasive health is defined using a metaphor of digital bubbles. A
      conceptual framework model focused on trustworthiness and privacy is then
      developed for pervasive health. On that model, principles and rules for trusted
      information management in pervasive health are defined. RESULTS: In the first
      phase of this study, a new definition of pervasive health was created. Using this
      model, differences between pervasive health and health care are stated. Reviewed
      publications demonstrate that the widely used principles of predefined and static
      trust cannot guarantee trustworthiness and privacy in pervasive health. Instead,
      such an environment requires personal dynamic and context-aware policies,
      awareness, and transparency. A conceptual framework model focused on information
      processing in pervasive health is developed. Using features of pervasive health
      and relations from the framework model, new principles for trusted pervasive
      health have been developed. The principles propose that personal health data
      should be under control of the data subject. The person shall have the right to
      verify the level of trust of any system which collects or processes his or her
      health information. Principles require that any stakeholder or system collecting
      or processing health data must support transparency and shall publish its trust
      and privacy attributes and even its domain specific policies. CONCLUSIONS: The
      developed principles enable trustworthiness and guarantee privacy in pervasive
      health. The implementation of principles requires new infrastructural services
      such as trust verification and policy conflict resolution. After implementation,
      the accuracy and usability of principles should be analyzed.

PMID- 22481298
TI  - High accuracy of the nine equivalents of nursing manpower use score assessed by
      critical care nurses.
AB  - PRINCIPLES: The nine equivalents of nursing manpower use score (NEMS) is
      frequently used to quantify, evaluate and allocate nursing workload at intensive
      care unit level. In Switzerland it has also become a key component in defining
      the degree of ICU hospital reimbursement. The accuracy of nurse registered NEMS
      scores in real life was assessed and error-prone variables were identified.
      METHODS: In this retrospective multicentre audit three reviewers (1 nurse, 2
      intensivists) independently reassessed a total of 529 NEMS scores. Correlation
      and agreement of the sum-scores and of the different variables among reviewers,
      as well as between nurses and the reviewers' reference value, were assessed (ICC,
      % agreement and kappa). Bland & Altman (reference value - nurses) of sum-scores
      and regression of the difference were determined and a logistic regression model
      identifying risk factors for erroneous assessments was calculated. RESULTS:
      Agreement for sum-scores among reviewers was almost perfect (mean ICC = 0.99 /
      significant correlation p <0.0001). The nurse registered NEMS score (mean +/- SD)
      was 24.8 +/- 8.6 points versus 24.0 +/- 8.6 points (p <0.13 for difference) of
      the reference value, with a slightly lower ICC (0.83). The lowest agreement was
      found in intravenous medication (0.85). Bland & Altman was 0.84 +/- 10, with a
      significant regression between the difference and the reference value, indicating
      overall an overestimation of lower scores (<=29 points) and underestimation of
      higher scores. Accuracy of scores or variables was not associated with nurses'
      characteristics. CONCLUSIONS: In real life, nurse registered NEMS scores are
      highly accurate. Lower (<=29 points) NEMS sum-scores are overestimated and higher
      underestimated. Accuracy of scores or variables was not associated with nurses'
      characteristics.

PMID- 22481299
TI  - Novel cholesterol feeding strategy enables a high-density cultivation of
      cholesterol-dependent NS0 cells in linear low-density polyethylene-based
      disposable bioreactors.
AB  - We have developed a perfusion-based high cell density (HD) cell banking and
      inoculum expansion procedure for a cholesterol-dependent NS0 myeloma cell line
      using linear low-density polyethylene-based disposable bioreactors. Challenges
      associated with cholesterol-polymer interactions, which suppress cholesterol
      dependent NS0 myeloma cell growth, were overcome using a novel cholesterol
      feeding protocol that included a combination of two cholesterol formulations: an
      ethanol-based formulation and an aqueous formulation. Using a cholesterol feed
      optimized for HD cell culture in a disposable bioreactor perfusion system, cell
      densities of >25 * 10(6) viable cells/ml at >= 90 % cell viability were achieved.
      Vials of high density cell banks were created by filling 90-100 * 10(6) viable
      cells/ml in 5 ml cryotube vials. Implementation of the HD cell banks enabled a
      significant reduction in the number of step operations in the inoculum expansion
      phase in a large-scale manufacturing setting.

PMID- 22481300
TI  - Endo-xylanase GH11 activation by the fungal metabolite eugenitin.
AB  - Eugenitin, a chromone derivative and a metabolite of the endophyte
      Mycoleptodiscus indicus, at 5 mM activated a recombinant GH11 endo-xylanase by 40
      %. The in silico prediction of ligand-binding sites on the three-dimensional
      structure of the endo-xylanase revealed that eugenitin interacts mainly by a
      hydrogen bond with a serine residue and a stacking interaction of the
      heterocyclic aromatic ring system with a tryptophan residue. Eugenitin improved
      the GH11 endo-xylanase activity on different substrates, modified the optimal pH
      and temperature activities and slightly affected the kinetic parameters of the
      enzyme.

PMID- 22481302
TI  - Age- and sex-specific risks of colorectal cancers in diabetic patients.
AB  - Diabetes has been reported to increase the risk of colorectal neoplasm in most
      but not all studies.  However, the data on age- and sex-specific incidence rates
      and relative risks associated with diabetes are limited.  We carried out this
      population-based cohort study to investigate the overall sex- and age-specific
      risks of colorectal cancer in association with diabetes.  Diabetic patients (n =
      615,532) and age- and sex-matched control individuals (n = 614,871), selected
      from the claim datasets, were followed up from 2000 to 2006.  The rates of
      admission due to colon and rectum cancers were estimated using the person-years
      approach, and the age- and sex-specific hazard ratio (HR) for both the
      malignancies were determined using the Cox regression model.  The overall
      incidence rate of colon cancer was 9.94 per 10,000 patient-years for the diabetic
      patients, as opposed to 7.84 per 10,000 patient-years for the control-group
      patients.  The corresponding observation for rectal cancer was 7.16 and 6.28 per
      10,000 patient-years.  Diabetic patients aged >= 45 years had significantly high
      HRs for developing colon cancer (1.20-1.45-fold).  We also noted a significantly
      high HR of rectal cancer in diabetic men (1.18-fold) aged >= 45 years, but not in
      diabetic women.  In conclusion, diabetes may significantly increase the risk of
      colorectal cancer, especially in patients aged 45-64 years.  Diabetologists
      should keep this relationship in mind while treating middle-aged diabetic men and
      should also advise these patients to undergo regular screening tests for
      colorectal cancer.

PMID- 22481301
TI  - Bioactive compounds synthesized by non-ribosomal peptide synthetases and type-I
      polyketide synthases discovered through genome-mining and metagenomics.
AB  - Non-ribosomal peptide synthetases (NRPS) and type-I polyketide synthases (PKS-I)
      are multimodular enzymes involved in biosynthesis of oligopeptide and polyketide
      secondary metabolites produced by microorganisms such as bacteria and fungi. New
      findings regarding the mechanisms underlying NRPS and PKS-I evolution illustrate
      how microorganisms expand their metabolic potential. During the last decade rapid
      development of bioinformatics tools as well as improved sequencing and annotation
      of microbial genomes led to discovery of novel bioactive compounds synthesized by
      NRPS and PKS-I through genome-mining. Taking advantage of these technological
      developments metagenomics is a fast growing research field which directly studies
      microbial genomes or specific gene groups and their products. Discovery of novel
      bioactive compounds synthesized by NRPS and PKS-I will certainly be accelerated
      through metagenomics, allowing the exploitation of so far untapped microbial
      resources in biotechnology and medicine.

PMID- 22481303
TI  - Knockdown of checkpoint kinase 1 is associated with the increased
      radiosensitivity of glioblastoma stem-like cells.
AB  - Glioblastoma multiforme is an aggressive brain tumor with a poor prognosis. The
      glioblastoma stem-like cells (GSCs) represent a rare fraction of human
      glioblastoma cells with the capacity for multi-lineage differentiation, self
      renewal and exact recapitulation of the original tumor. Interestingly, GSCs are
      more radioresistant compared with other tumor cells. In addition, the remarkable
      radioresistance of GSCs has been known to promote radiotherapy failure and
      therefore is associated with a significantly higher risk of a local tumor
      recurrence. Moreover, the hyperactive cell cycle checkpoint kinase (Chk) 1 and 2
      play a pivotal role in the DNA damage response including radiation and chemical
      therapy. Based on aforementioned, we hypothesized that knockdown of Chk1 or Chk2
      might confer radiosensitivity on GSCs and thereby increases the efficiency of
      radiotherapy. In this study, we knocked down the expression of Chk1 or Chk2 in
      human GSCs using lentivirus-delivered short hairpin RNA (shRNA) to examine its
      effect on the radiosensitivity. After radiation, the apoptosis rate and the cell
      cycle of GSCs were measured with Flow Cytometry. Compared with control GSCs
      (apoptosis, 7.82 +/- 0.38%; G2/M arrest, 60.20 +/- 1.28%), Chk1 knockdown in GSCs
      increased the apoptosis rate (37.87 +/- 0.32%) and decreased the degree of the
      G2/M arrest (22.37 +/- 2.01%). In contrast, the radiosensitivity was not enhanced
      by Chk2 knockdown in GSCs. These results suggest that depletion of Chk1 may
      improve the radio-sensitivity of GSCs via inducing cell apoptosis. In summary,
      the therapy targeting Chk1 gene in the GSCs may be a novel way to treat
      glioblastoma.

PMID- 22481304
TI  - Moss cushions facilitate water and nutrient supply for plant species on bare
      limestone pavements.
AB  - Dense moss cushions of different size are distributed across the bare limestone
      pavements on Oland, SE Sweden. Increasing cushion size is predicted to physically
      protect and improve performance and colonization by vascular plants. Therefore,
      we tested water balance, phosphorus supply, and species richness, and evaluated
      duration of plant activity during desiccation as a function of ground area, for a
      large collection of moss cushions. We found that lower evaporation and higher
      water storage contributed equally to extending the desiccation period with
      increasing cushion size. Evaporation rates declined by the -0.36 power of cushion
      diameter, and were not significantly different from -0.50 for the square root
      function previously predicted for the increasing thickness of the boundary layer,
      with greater linear dimensions for smooth flat objects at low wind velocities.
      Size dependence vanished under stagnant conditions. One moss species was added to
      the species pool for every nine-fold increase in cushion area. Vascular plants
      were absent from the smallest cushions, whereas one or two species, on average,
      appeared in 375- and 8,500-cm(2) cushions with water available for 6 and 10 days
      during desiccation. Phosphorus concentrations increased stepwise and four-fold
      from detritus to surface mosses and to vascular plants, and all three pools
      increased with cushion size. We conclude that cushion mosses and cushion size
      play a critical role in this resource-limited limestone environment by offering
      an oasis of improved water and nutrient supply to colonization and growth of
      plants.

PMID- 22481305
TI  - Facilitative interactions do not wane with warming at high elevations in the
      Andes.
AB  - Positive interactions between species are known to play an important role in the
      structure and dynamics of alpine plant communities. The balance between negative
      and positive interactions is known to shift along spatial and temporal gradients,
      with positive effects prevailing over negative ones as the environmental stress
      increases. Thus, this balance is likely to be affected by climate change. We
      hypothesized that increases in temperature (a global warming scenario) should
      decrease the importance of positive interactions for the survival and growth of
      alpine plant species. To test this hypothesis, we selected individuals of the
      native grass species Hordeum comosum growing within the nurse cushion species
      Azorella madreporica at 3,600 m.a.s.l. in Los Andes (Chile), and performed nurse
      removal and seedling survival experiments under natural and warmer conditions.
      For warmer conditions, we used open-top chambers, which increased the temperature
      by 4  degrees C. After two growing seasons, we compared the effect of nurse
      removal on the survival, biomass, and photochemical efficiency of H. comosum
      individuals under warmer and natural conditions. Nurse removal significantly
      decreased the survival, biomass, and photochemical efficiency of H. comosum,
      demonstrating the facilitative effects of nurse cushions. Seedling survival was
      also enhanced by cushions, even under warmer conditions. However, warmer
      conditions only partially mitigated the negative effects of nurse removal,
      suggesting that facilitative effects of cushions do not wane under warmer
      conditions. Thus, facilitative interactions are vital to the performance and
      survival of alpine species, and these positive interactions will continue to be
      important in the warmer conditions of the future in high-alpine habitats.

PMID- 22481306
TI  - Physiology of the seasonal relationship between the photochemical reflectance
      index and photosynthetic light use efficiency.
AB  - The photochemical reflectance index (PRI) is regarded as a promising proxy to
      track the dynamics of photosynthetic light use efficiency (LUE) via remote
      sensing. The implementation of this approach requires the relationship between
      PRI and LUE to scale not only in space but also in time. The short-term
      relationship between PRI and LUE is well known and is based on the regulative
      process of non-photochemical quenching (NPQ), but at the seasonal timescale the
      mechanisms behind the relationship remain unclear. We examined to what extent
      sustained forms of NPQ, photoinhibition of reaction centres, seasonal changes in
      leaf pigment concentrations, or adjustments in the capacity of alternative energy
      sinks affect the seasonal relationship between PRI and LUE during the year in
      needles of boreal Scots pine. PRI and NPQ were highly correlated during most of
      the year but decoupled in early spring when the foliage was deeply downregulated.
      This phenomenon was attributed to differences in the physiological mechanisms
      controlling the seasonal dynamics of PRI and NPQ. Seasonal adjustments in the
      pool size of the xanthophyll cycle pigments, on a chlorophyll basis, controlled
      the dynamics of PRI, whereas the xanthophyll de-epoxidation status and other
      xanthophyll-independent mechanisms controlled the dynamics of NPQ at the seasonal
      timescale. We conclude that the PRI leads to an underestimation of NPQ, and
      consequently overestimation of LUE, under conditions of severe stress in
      overwintering Scots pine, and most likely also in species experiencing severe
      drought. This severe stress-induced decoupling may challenge the implementation
      of the PRI approach.

PMID- 22481307
TI  - The association of acculturation and health literacy, numeracy and health-related
      skills in Spanish-speaking caregivers of young children.
AB  - Little is known about the relationship among acculturation, literacy, and health
      skills in Latino caregivers of young children. Latino caregivers of children < 30
      months seeking primary care at four medical centers were administered measures of
      acculturation (SASH), functional health literacy (STOFHLA), numeracy (WRAT-3) and
      health-related skills (PHLAT Spanish). Child anthropomorphics and immunization
      status were ascertained by chart review. Caregivers (N = 184) with a median age
      of 27 years (IQR: 23-32) participated; 89.1% were mothers, and 97.1% had low
      acculturation. Lower SASH scores were significantly correlated (P < 0.01) with
      lower STOFHLA (rho = 0.21), WRAT-3 (rho = 0.25), and PHLAT Spanish scores (rho =
      0.34). SASH scores predicted PHLAT Spanish scores in a multivariable linear
      regression model that adjusted for the age of child, the age and gender of the
      caregiver, number of children in the family, the type of health insurance of the
      caregiver, and study site (adjusted beta: 0.84, 95% CI 0.26-1.42, P = 0.005).
      This association was attenuated by the addition of literacy (adjusted beta: 0.66,
      95% CI 0.11-1.21, P = 0.02) or numeracy (adjusted beta: 0.50, 95% CI -0.04-1.04,
      P = 0.07) into the model. There was no significant association between
      acculturation and up-to-date child immunizations or a weight status of
      overweight/obese. Lower acculturation was associated with worse health literacy
      and diminished ability to perform child health-related skills. Literacy and
      numeracy skills attenuated the association between acculturation and child health
      skills. These associations may help to explain some child health disparities in
      Latino communities.

PMID- 22481309
TI  - Insights into the 1.59-Mbp largest plasmid of Azospirillum brasilense CBG497.
AB  - The plant growth-promoting proteobacterium Azospirillum brasilense enhances
      growth of many economically important crops, such as wheat, maize, and rice. The
      sequencing and annotation of the 1.59-Mbp replicon of A. brasilense CBG497, a
      strain isolated from a maize rhizosphere grown on an alkaline soil in the
      northeast of Mexico, revealed a GC content of 68.7 % and the presence of 1,430
      potential protein-encoding genes, 1,147 of them classified into clusters of
      orthologous groups categories, and 16 tRNA genes representing 11 tRNA species.
      The presence of sixty-two genes representatives of the minimal gene set and
      chromid core genes suggests its importance in bacterial survival. The phaAB -> G
      operon, reported as involved in the bacterial adaptation to alkaline pH in the
      presence of K(+), was also found on this replicon and detected in several
      Azospirillum strains. Phylogenetic analysis suggests that it was laterally
      acquired. We were not able to show its inference on the adaptation to basic pH,
      giving a hint about the presence of an alternative system for adaptation to
      alkaline pH.

PMID- 22481308
TI  - Migration status in relation to clinical characteristics and barriers to care
      among youth with diabetes in the US.
AB  - Migration status and the accompanying diversity in culture, foods and family
      norms, may be an important consideration for practitioners providing
      individualized care to treat and prevent complications among youth with diabetes.
      Approximately 20 % of youth in the US have >=1 foreign-born parent. However, the
      proportion and characteristics of youth with diabetes and >=1 foreign-born parent
      have yet to be described. Study participants (n = 3,086) were from SEARCH for
      Diabetes in Youth, a prospective multi-center study in the US. Primary outcomes
      of interest included HbA1c, body mass index and barriers to care. Multivariable
      analyses were carried out using logistic regression and analysis of covariance.
      Approximately 17 % of participants with type 1 diabetes (T1D) and 22 % with type
      2 diabetes (T2D) had >=1 foreign-born parent. Youth with T1D and >=1 foreign-born
      parent were less likely to have poor glycemic control [adjusted odds ratio (OR)
      (95 % confidence interval): 0.70 (0.53, 0.94)]. Among youth with T2D, those with
      >=1 foreign-born parent had lower odds of obesity [adjusted OR (95 % CI): 0.35
      (0.17, 0.70)]. This is the first study to estimate the proportion and
      characteristics of youth with diabetes exposed to migration in the US. Research
      into potential mechanisms underlying the observed protective effects is
      warranted.

PMID- 22481310
TI  - Interactions of sulfur oxidation repressor with its promoters involve different
      binding geometries.
AB  - The divergently transcribed sulfur oxidation (sox) operon of a sulfur
      chemolithotrophs, Pseudaminobacter salicylatoxidans KCT001, comprising sox TRS-VW
      XYZABCD, is regulated by a repressor (SoxR). SoxR binds to two disparate
      operators, sv (present in between soxS and soxV) and wx (present in between soxW
      and soxX). Here we report details of the interaction between SoxR and these two
      operator regions of the sox operon, using methylation interference and hydroxyl
      radical footprinting. We propose that the sv operator is symmetric and compact,
      while the wx operator is asymmetric and extended. We report an interesting
      difference between the SoxR-sv interaction and the SoxR-wx interaction through a
      competition assay involving groove-specific ligands. SoxR binds in the major
      groove of the sv operator, but binds in the minor groove of the wx operator. The
      structural flexibility of the SoxR helps it to act differentially in its
      interactions with these two operators. Mutational analysis shows that SoxR uses
      different amino acid residues when binding to the sv operator versus the wx
      operator. Taken together, the results indicate that interaction between SoxR and
      the two operator sites involves different binding geometries. This makes SoxR the
      only known example of a ArsR-family protein that binds differentially to
      different operators.

PMID- 22481311
TI  - Properties of nanoparticles prepared from NdFeB-based compound for magnetic
      hyperthermia application.
AB  - Nanoparticles were prepared from a NdFeB-based alloy using the hydrogen
      decrepitation process together with high-energy ball milling and tested as
      heating agent for magnetic hyperthermia. In the milling time range evaluated (up
      to 10 h), the magnetic moment per mass at H = 1.59 MA m(-1) is superior than 70 A
      m(2) kg(-1); however, the intrinsic coercivity might be inferior than 20 kA m(
      1). The material presents both ferromagnetic and superparamagnetic particles
      constituted by a mixture of phases due to the incomplete disproportionation
      reaction of Nd(2)Fe(14)BH(x) during milling. Solutions prepared with deionized
      water and magnetic particles exposed to an AC magnetic field (H(max) ~ 3.7 kA m(
      1) and f = 228 kHz) exhibited 26 K <= DeltaT(max) <= 44 K with a maximum
      estimated specific absorption rate (SAR) of 225 W kg(-1). For the pure magnetic
      material milled for the longest period of time (10 h), the SAR was estimated as
      ~2500 W kg(-1). In vitro tests indicated that the powders have acceptable
      cytotoxicity over a wide range of concentration (0.1-100 ug ml(-1)) due to the
      coating applied during milling.

PMID- 22481312
TI  - Stereodynamics of multistate roaming.
AB  - We present a molecular level description of NO3-> NO + O2 photodissociation for
      both of the experimentally observed reaction pathways using the results of ion
      imaging experiments and recent theoretical studies. Vector correlation and Lambda
      doublet propensity measurements have been performed on state-selected NO
      fragments in order to further characterize the stereodynamics of this reaction.
      Previous measurements (Grubb et al., Science, 2012, 1075-1078) of relative Lambda
      doublet propensities along with ab initio calculations revealed that both
      pathways arise from roaming-type mechanisms, but each pathway arises from roaming
      on a different electronic potential. This model, however, assumes that NO3
      dissociation takes place in the molecular plane. In the present paper, we have
      confirmed this assumption through speed-dependent vector correlation
      measurements. Strong perpendicular correlations between the velocity vector v and
      the angular momentum vector j are observed in the NO fragment originating from
      both pathways, in agreement with a constrained planar dissociation. These results
      are discussed in light of the absence of vector correlations in other roaming
      systems, which have previously been characterized by an unconstrained intra
      molecular abstraction. We show that geometrical constraints should in fact be
      quite prevalent in roaming dynamics, and are analogous to the geometrical
      constraints of the corresponding bimolecular abstraction reaction. 

PMID- 22481314
TI  - Complete noise analysis of a simple force spectroscopy AFM setup and its
      applications to study nanomechanics of mammalian Notch 1 protein.
AB  - We describe a complete noise analysis and application of a custom made AFM force
      spectroscopy setup on pulling a recombinant protein with an NRR domain of mouse
      Notch 1. Our table top AFM setup is affordable, has an open architecture, and is
      easily transferable to other laboratories. Its calculated noise characteristics
      are dominated by the Brownian noise with 2% non-Brownian components integrated
      over the first thermally induced resonance of a typical cantilever. For a typical
      SiN cantilever with a force constant of ~15 pN nm(-1) and in water the force
      sensitivity and resolution are less than 10 pN, and the corresponding deflection
      sensitivities are less than 100 pm Hz(-1/2). Also, we obtain a sub-ms time
      resolution in detecting the protein length change, and only few ms cantilever
      response times as measured in the force clamp mode on a well-known protein
      standard. Using this setup we investigate force-induced conformational
      transitions in the NRR region of a mouse Notch 1. Notch is an important protein
      related to leukemia and breast cancers in humans. We demonstrate that it is
      feasible to develop AFM-based studies of the force-induced conformational
      transitions in Notch. Our results match recent steered molecular dynamics
      simulations of the NRR unfolding and constitute a first step towards a detailed
      study of Notch activation with AFM.

PMID- 22481313
TI  - Effects of habitual diet on ethnic differences in serum total ghrelin.
AB  - Ghrelin, an orexigenic hormone, may be involved in the etiology of obesity.
      African Americans (AA) experience higher obesity rates than European Americans
      (EA), but it is unclear whether ghrelin differs with ethnicity. This study was
      designed to compare ghrelin concentrations between overweight AA and EA adults in
      a post absorptive state, in response to a standard meal, and after 8-week
      habituation to diets of differing macronutrient profiles. Sixty-one overweight
      men and women (31 EA and 30 AA) were assigned to either a higher
      carbohydrate/lower-fat diet (55% CHO, 18% PRO, 27% FAT) or a lower
      carbohydrate/higher-fat diet (43% CHO, 18% PRO, 39% FAT) for 8 weeks. At baseline
      and week 8, participants ingested a standard liquid mixed meal. Blood was sampled
      before the meal and serially after ingestion to measure total ghrelin and
      insulin. Hunger was assessed with a visual analog scale. Composite scores for
      ghrelin, insulin, and hunger were calculated as area under the curve (AUC), and
      ghrelin suppression was calculated as the change from fasting concentration.
      Fasting ghrelin and ghrelin AUC were higher among EA at baseline and week 8 (p <
      0.001), and these differences were not affected by diet habituation. Despite
      greater postprandial ghrelin suppression, EA displayed greater hunger immediately
      following the test meal (p < 0.05). Overweight EA displayed higher circulating
      ghrelin and greater ghrelin suppression compared to AA. Further study is
      warranted to explore the physiological basis for these ethnic differences and to
      determine whether they may relate to higher obesity rates among AA.

PMID- 22481315
TI  - Bolstering the link.

PMID- 22481316
TI  - Creative tensions.

PMID- 22481317
TI  - Into the depths.

PMID- 22481318
TI  - The inconvenient truth of carbon offsets.

PMID- 22481329
TI  - Physicists hunt for dark forces.

PMID- 22481331
TI  - US integrity effort hits troubled water.

PMID- 22481330
TI  - Cyprus Institute loses money and support.

PMID- 22481332
TI  - A data-driven war on crime.

PMID- 22481333
TI  - Glaciologists to target third pole.

PMID- 22481335
TI  - PhDs leave the ivory tower.

PMID- 22481336
TI  - Infectious disease: Blowing in the wind.

PMID- 22481337
TI  - Brain imaging: fMRI 2.0.

PMID- 22481338
TI  - Research efficiency: Clean up the waste.

PMID- 22481339
TI  - Research efficiency: Perverse incentives.

PMID- 22481340
TI  - Research efficiency: Turn the scientific method on ourselves.

PMID- 22481345
TI  - Publishing: Journals' role in ethical research.

PMID- 22481346
TI  - Media centre: vital to US science.

PMID- 22481347
TI  - Artificial microbes: Balanced regulation of synthetic biology.

PMID- 22481348
TI  - Media centre: more than public relations.

PMID- 22481349
TI  - David Sayre (1924-2012).

PMID- 22481350
TI  - Complex systems: Spotlight on mobility.

PMID- 22481351
TI  - Climate change: A tale of two hemispheres.

PMID- 22481352
TI  - Neuroscience: The symphony of choice.

PMID- 22481353
TI  - Atomic physics: An almost lightless laser.

PMID- 22481354
TI  - Cancer: Limitations of therapies exposed.

PMID- 22481355
TI  - Genomics: Stickleback is the catch of the day.

PMID- 22481357
TI  - Global warming preceded by increasing carbon dioxide concentrations during the
      last deglaciation.
AB  - The covariation of carbon dioxide (CO(2)) concentration and temperature in
      Antarctic ice-core records suggests a close link between CO(2) and climate during
      the Pleistocene ice ages. The role and relative importance of CO(2) in producing
      these climate changes remains unclear, however, in part because the ice-core
      deuterium record reflects local rather than global temperature. Here we construct
      a record of global surface temperature from 80 proxy records and show that
      temperature is correlated with and generally lags CO(2) during the last (that is,
      the most recent) deglaciation. Differences between the respective temperature
      changes of the Northern Hemisphere and Southern Hemisphere parallel variations in
      the strength of the Atlantic meridional overturning circulation recorded in
      marine sediments. These observations, together with transient global climate
      model simulations, support the conclusion that an antiphased hemispheric
      temperature response to ocean circulation changes superimposed on globally in
      phase warming driven by increasing CO(2) concentrations is an explanation for
      much of the temperature change at the end of the most recent ice age.

PMID- 22481359
TI  - RR-Lyrae-type pulsations from a 0.26-solar-mass star in a binary system.
AB  - RR Lyrae pulsating stars have been extensively used as tracers of old stellar
      populations for the purpose of determining the ages of galaxies, and as tools to
      measure distances to nearby galaxies. There was accordingly considerable interest
      when the RR Lyrae star OGLE-BLG-RRLYR-02792 (referred to here as RRLYR-02792) was
      found to be a member of an eclipsing binary system, because the mass of the
      pulsator (hitherto constrained only by models) could be unambiguously determined.
      Here we report that RRLYR-02792 has a mass of 0.26 solar masses M[symbol see
      text] and therefore cannot be a classical RR Lyrae star. Using models, we find
      that its properties are best explained by the evolution of a close binary system
      that started with M[symbol see text] and 0.8M[symbol see text]stars orbiting each
      other with an initial period of 2.9 days. Mass exchange over 5.4 billion years
      produced the observed system, which is now in a very short-lived phase where the
      physical properties of the pulsator happen to place it in the same instability
      strip of the Hertzsprung-Russell diagram as that occupied by RR Lyrae stars. We
      estimate that only 0.2 per cent of RR Lyrae stars may be contaminated by systems
      similar to this one, which implies that distances measured with RR Lyrae stars
      should not be significantly affected by these binary interlopers.

PMID- 22481358
TI  - The genomic basis of adaptive evolution in threespine sticklebacks.
AB  - Marine stickleback fish have colonized and adapted to thousands of streams and
      lakes formed since the last ice age, providing an exceptional opportunity to
      characterize genomic mechanisms underlying repeated ecological adaptation in
      nature. Here we develop a high-quality reference genome assembly for threespine
      sticklebacks. By sequencing the genomes of twenty additional individuals from a
      global set of marine and freshwater populations, we identify a genome-wide set of
      loci that are consistently associated with marine-freshwater divergence. Our
      results indicate that reuse of globally shared standing genetic variation,
      including chromosomal inversions, has an important role in repeated evolution of
      distinct marine and freshwater sticklebacks, and in the maintenance of divergent
      ecotypes during early stages of reproductive isolation. Both coding and
      regulatory changes occur in the set of loci underlying marine-freshwater
      evolution, but regulatory changes appear to predominate in this well known
      example of repeated adaptive evolution in nature.

PMID- 22481360
TI  - A steady-state superradiant laser with less than one intracavity photon.
AB  - The spectral purity of an oscillator is central to many applications, such as
      detecting gravity waves, defining the second, ground-state cooling and quantum
      manipulation of nanomechanical objects, and quantum computation. Recent proposals
      suggest that laser oscillators which use very narrow optical transitions in atoms
      can be orders of magnitude more spectrally pure than present lasers. Lasers of
      this high spectral purity are predicted to operate deep in the 'bad-cavity', or
      superradiant, regime, where the bare atomic linewidth is much less than the
      cavity linewidth. Here we demonstrate a Raman superradiant laser source in which
      spontaneous synchronization of more than one million rubidium-87 atomic dipoles
      is continuously sustained by less than 0.2 photons on average inside the optical
      cavity. By operating at low intracavity photon number, we demonstrate isolation
      of the collective atomic dipole from the environment by a factor of more than ten
      thousand, as characterized by cavity frequency pulling measurements. The emitted
      light has a frequency linewidth, measured relative to the Raman dressing laser,
      that is less than that of single-particle decoherence linewidths and more than
      ten thousand times less than the quantum linewidth limit typically applied to
      'good-cavity' optical lasers, for which the cavity linewidth is much less than
      the atomic linewidth. These results demonstrate several key predictions for
      future superradiant lasers, which could be used to improve the stability of
      passive atomic clocks and which may lead to new searches for physics beyond the
      standard model.

PMID- 22481361
TI  - Decoherence-protected quantum gates for a hybrid solid-state spin register.
AB  - Protecting the dynamics of coupled quantum systems from decoherence by the
      environment is a key challenge for solid-state quantum information processing. An
      idle quantum bit (qubit) can be efficiently insulated from the outside world by
      dynamical decoupling, as has recently been demonstrated for individual solid
      state qubits. However, protecting qubit coherence during a multi-qubit gate is a
      non-trivial problem: in general, the decoupling disrupts the interqubit dynamics
      and hence conflicts with gate operation. This problem is particularly salient for
      hybrid systems, in which different types of qubit evolve and decohere at very
      different rates. Here we present the integration of dynamical decoupling into
      quantum gates for a standard hybrid system, the electron-nuclear spin register.
      Our design harnesses the internal resonance in the coupled-spin system to resolve
      the conflict between gate operation and decoupling. We experimentally demonstrate
      these gates using a two-qubit register in diamond operating at room temperature.
      Quantum tomography reveals that the qubits involved in the gate operation are
      protected as accurately as idle qubits. We also perform Grover's quantum search
      algorithm, and achieve fidelities of more than 90% even though the algorithm run
      time exceeds the electron spin dephasing time by two orders of magnitude. Our
      results directly allow decoherence-protected interface gates between different
      types of solid-state qubit. Ultimately, quantum gates with integrated decoupling
      may reach the accuracy threshold for fault-tolerant quantum information
      processing with solid-state devices.

PMID- 22481362
TI  - Past extreme warming events linked to massive carbon release from thawing
      permafrost.
AB  - Between about 55.5 and 52 million years ago, Earth experienced a series of sudden
      and extreme global warming events (hyperthermals) superimposed on a long-term
      warming trend. The first and largest of these events, the Palaeocene-Eocene
      Thermal Maximum (PETM), is characterized by a massive input of carbon, ocean
      acidification and an increase in global temperature of about 5  degrees C within
      a few thousand years. Although various explanations for the PETM have been
      proposed, a satisfactory model that accounts for the source, magnitude and timing
      of carbon release at the PETM and successive hyperthermals remains elusive. Here
      we use a new astronomically calibrated cyclostratigraphic record from central
      Italy to show that the Early Eocene hyperthermals occurred during orbits with a
      combination of high eccentricity and high obliquity. Corresponding climate
      ecosystem-soil simulations accounting for rising concentrations of background
      greenhouse gases and orbital forcing show that the magnitude and timing of the
      PETM and subsequent hyperthermals can be explained by the orbitally triggered
      decomposition of soil organic carbon in circum-Arctic and Antarctic terrestrial
      permafrost. This massive carbon reservoir had the potential to repeatedly release
      thousands of petagrams (10(15) grams) of carbon to the atmosphere-ocean system,
      once a long-term warming threshold had been reached just before the PETM.
      Replenishment of permafrost soil carbon stocks following peak warming probably
      contributed to the rapid recovery from each event, while providing a sensitive
      carbon reservoir for the next hyperthermal. As background temperatures continued
      to rise following the PETM, the areal extent of permafrost steadily declined,
      resulting in an incrementally smaller available carbon pool and smaller
      hyperthermals at each successive orbital forcing maximum. A mechanism linking
      Earth's orbital properties with release of soil carbon from permafrost provides a
      unifying model accounting for the salient features of the hyperthermals.

PMID- 22481363
TI  - A gigantic feathered dinosaur from the lower cretaceous of China.
AB  - Numerous feathered dinosaur specimens have recently been recovered from the
      Middle-Upper Jurassic and Lower Cretaceous deposits of northeastern China, but
      most of them represent small animals. Here we report the discovery of a gigantic
      new basal tyrannosauroid, Yutyrannus huali gen. et sp. nov., based on three
      nearly complete skeletons representing two distinct ontogenetic stages from the
      Lower Cretaceous Yixian Formation of Liaoning Province, China. Y. huali shares
      some features, particularly of the cranium, with derived tyrannosauroids, but is
      similar to other basal tyrannosauroids in possessing a three-fingered manus and a
      typical theropod pes. Morphometric analysis suggests that Y. huali differed from
      tyrannosaurids in its growth strategy. Most significantly, Y. huali bears long
      filamentous feathers, thus providing direct evidence for the presence of
      extensively feathered gigantic dinosaurs and offering new insights into early
      feather evolution.

PMID- 22481365
TI  - Bisphenol A exposure, effects, and policy: a wildlife perspective.
AB  - Thousands of anthropogenic chemicals are present in the environment, and mounting
      evidence indicates that some have endocrine-disrupting effects in a variety of
      organisms. Of particular concern are chemicals that act as agonists or
      antagonists on vertebrate estrogen or androgen receptors. One such compound is
      bisphenol A (BPA), which appears to be both an estrogen receptor agonist and an
      androgen receptor antagonist. Used in the manufacture of plastic resins, BPA is
      found at low levels in surface-water, sediments, soils, and biota. Although it
      degrades quickly, it is pseudo-persistent in the environment because of continual
      inputs. Due to its environmental ubiquity, organisms may be exposed to BPA
      chronically or during sensitive life stages. While the impacts of BPA-related
      endocrine disruption in humans have been extensively studied, the endocrinal and
      systemic effects in wildlife are less well known. This article reviews the
      current state of knowledge of BPA inputs to the environment, routes of exposure,
      and effects on wildlife. We then critically examine the regulatory structure
      governing the environmental endpoints of BPA in the United States, European
      Union, and Canada, and discuss major challenges to the effective regulation of
      BPA. We conclude with a survey of treatment and mitigation options.

PMID- 22481366
TI  - Environmental impacts of hydroelectric power and other anthropogenic developments
      on the hydromorphology and ecology of the Durance channel and the Etang de Berre,
      southeast France.
AB  - The generation of electricity through hydropower can, along with other
      anthropogenic activities, degrade river hydromorphology and ecosystems. In this
      case, water for power generation is diverted from the River Durance to a canal,
      which services a chain of 17 power stations, with the lower three being in the
      catchment of the Etang de Berre. This means that excess water and sediments are
      discharged into the salt-water lagoon with enormous consequences for ecosystems
      there. This paper summarizes the impacts of HEP and other human activities on
      both the river and lagoonal systems. It also considers agency and government
      attempts to understand and counter the degradation of these systems, both to date
      and in the future, with the latter catering for the potential impacts of future
      human development and global warming.

PMID- 22481367
TI  - Molecular mechanistic model of plant heavy metal tolerance.
AB  - Plants being sessile are susceptible to heavy metals (HMs) toxicity and respond
      differentially to hostile environments. The toxicity of HM is governed by the
      type of ion and its concentration, plant physiology and stage of plant growth.
      Plants counteract the HMs stress by overexpressing numerous stress related
      proteins, glutathione mediated tolerance pathways and signaling proteins
      involving networks of various stress regulations. Though the response may vary
      and be specific in its stress networks regulation for each HM. The intricacy of
      HM tolerance response involves the set of molecular regulation, which demands to
      be understood to yield HM tolerant plant. Topical advancements in molecular
      biology and genomics have facilitated studies in transcriptomics and proteomics
      to identify regulatory genes implied in HM tolerance in plants. The integration
      of resources obtained through these studies will be of extreme significance,
      combining the diverse fields of plant biology to dissect the actual HM stress
      response network. In this review, we put an endeavor to describe the specific
      aspects of the molecular mechanisms of a plant response to HMs which may
      contribute to better understanding of the mode of HMs action and overlaps in
      metal sensing and signaling/crosstalk to other stresses.

PMID- 22481368
TI  - Proteomic analysis of a drosophila IBMPFD model reveals potential pathogenic
      mechanisms.
AB  - IBMPFD, Inclusion body myopathy associated with Paget's disease of bone and
      frontotemporal dementia, is a hereditary degenerative disorder due to single
      missense mutations in VCP (Valosin-Containing Protein). The mechanisms of how
      mutations of VCP lead to IBMPFD remain mysterious. Here we utilize two
      dimensional difference gel electrophoresis (2D-DIGE) combined with mass
      spectrometry to study the IBMPFD disorder at the protein level. With this set-up,
      we are able to employ comparative proteomics to analyze IBMPFD disease using
      Drosophila melanogaster as our disease model organism. Head proteome of
      transgenic D. melanogaster expressing wild type VCP is compared, respectively,
      with the head proteome of transgenic mutant type VCPs that correspond to human
      IBMPFD disease alleles (TER94(A229E), TER94(R188Q), and TER94(R152H)). Of all the
      proteins identified, a significant fraction of proteins altered in TER94(A229E)
      and TER94(R188Q) mutants belong to the same functional categories, i.e. apoptosis
      and metabolism. Among these, Drosophila transferrin is observed to be
      significantly up-regulated in mutant flies expressing TER94(A229E). A knock-down
      experiment suggests that fly transferrin might be a potential modifier in IBMPFD
      disease. The molecular analysis of IBMPFD disease may benefit from the proteomics
      approach which combines the advantages of high throughput analysis and the focus
      on protein levels.

PMID- 22481369
TI  - Dementia with Lewy bodies: the principles of diagnostics, treatment, and
      management.
AB  - Dementia with Lewy bodies was first recognized as a separate entity about 30
      years ago. The prevalence varies from 0% to 5% in the general population, and
      this disease accounts for 0% to 30.5% of all dementia cases. Dementia with Lewy
      bodies is considered the second most common cause of degenerative dementia after
      Alzheimer's disease. The disease is characterized by alpha-synuclein
      immunoreactive protein deposits in both neurons and glial cells. The protein
      deposits are especially prominent in dopaminergic neurons, where they can be
      detected using conventional histological stains, such as hematoxylin and eosin,
      and are commonly referred to as Lewy bodies. The diagnosis of dementia with Lewy
      bodies is based on the presence of dementia as well as 2 of the following 3 core
      diagnostic features: 1) fluctuating cognition, 2) visual hallucinations, and 3)
      movement disorder. Diagnostic tests include laboratory data, structural and
      functional imaging, and electroencephalography. Differential diagnosis of
      dementia with Lewy bodies focuses on other later life dementia syndromes, other
      parkinsonian diseases (Parkinson's disease, progressive supranuclear palsy,
      corticobasal degeneration), and primary psychiatric illnesses. There is type 1b
      evidence to support treatment with cholinesterase inhibitors. Glutamatergic and
      dopaminergic therapies are used as well. Standard neuroleptics are
      contraindicated, and atypical agents should be used cautiously. Nonpharmacologic
      measures - therapeutic environment, psychological and social support, physical
      activity, behavioral management strategies, caregivers' education and support,
      and different services - could be suggested.

PMID- 22481370
TI  - Introduction of novel semiquantitative evaluation of (99m)Tc-MIBI SPECT before
      and after treatment of glioma.
AB  - BACKGROUND AND OBJECTIVE. There is a need for objective semiquantitative indexes
      for the evaluation of results of single-photon emission tomography (SPECT) in
      patients with brain glioma. The aim of this study was to validate the total size
      index (TSI) and total intensity index (TII) based on technetium-99m
      methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT scans to discriminate the patients
      with high-grade glioma versus low-grade glioma and to evaluate the changes of
      viable glioma tissue by the means of TSI and TII after surgery and after
      radiation treatment. MATERIAL AND METHODS. Thirty-two patients (mean age, 55
      years [SD, 18]; 20 men) underwent a (99m)Tc-MIBI-SPECT scan before surgery. Of
      these patients, 27 underwent a postoperative (99m)Tc-MIBI-SPECT scan and 7
      patients with grade IV glioma underwent a third (99m)Tc-MIBI-SPECT scan after
      radiation treatment. TII that corresponds to the area and intensity of tracer
      uptake and TSI that corresponds to the area of tracer uptake were calculated
      before surgery, after surgery, and after radiation treatment. RESULTS. The TII
      and TSI were found to be valid in discriminating the patients with high-grade
      versus low-grade glioma with optimal cutoff values of 3.0 and 2.5, respectively.
      Glioma grade correlated with the preoperative TSI score (r=0.76, P<0.001) and
      preoperative TII score (r=0.64, P<0.001). There was a significant decrease in the
      TII and TSI after surgery in patients with grade IV glioma. After radiation
      treatment, there was a significant increase in the TII in patients with grade IV
      glioma. CONCLUSIONS. TSI and TII were found to be reliable in discriminating the
      patients with high-grade versus low-grade glioma and allowed for the
      semiquantitative evaluation of change in viable glioma tissue after surgery and
      after radiation treatment in patients with grade IV glioma.

PMID- 22481371
TI  - Prevalence of human papillomavirus types 16, 18, and 45 in women with cervical
      intraepithelial changes: associations with colposcopic and histological findings.
AB  - The aim of the study was to determine the prevalence of human papillomavirus
      (HPV) types 16, 18, and 45 in women with cervical intraepithelial changes caused
      by high-risk HPV in relation to colposcopic and histological findings. MATERIAL
      AND METHODS. A prospective study of 393 women with cervical cytologic changes
      confirmed by the Papanicolaou test was undertaken from April 3, 2006, to April 3,
      2007. The Hybrid Capture 2 assay was performed. HPV-positive women underwent
      genotyping for types 16, 18, and 45. Colposcopy and biopsy were performed in 317
      (80.7%) and 249 women (63.4%), respectively. The results were analyzed by age
      groups. RESULTS. Of all the women with cervical intraepithelial changes, 59% were
      positive for HR HPV, and 62% were positive for HPV types 16, 18, and 45. HPV
      types 16, 18, and 45 were detected in 54.8% of women with ASC-US/AGUS/ASC-H,
      50.0% of women with LSIL, and 75.6% of women with HSIL. After confirmation of any
      histological and colposcopic changes, HPV types 16, 18, and 45 were detected in
      68.0% and 69.0% of women, respectively. Moreover, 84.2% of the women with HSIL
      and high-grade colposcopic changes, and 78.5% of the women with HSIL and CIN
      2/CIN 2-3/CIN 3/carcinoma in situ were positive for HPV types 16, 18, and 45. The
      sensitivity of the Papanicolaou test together with the Hybrid Capture 2 test
      compared with the Papanicolaou test together with the HPV 16/18/45 test
      diagnosing CIN 2+ changes did not differ (96.7% vs. 97.1%), but the specificity
      was higher (40.3% vs. 8.0%). CONCLUSIONS. The majority of the cytologic,
      colposcopic, and histological changes were caused by HPV types 16, 18, and 45.
      Despite the high prevalence of HPV types 16, 18, and 45, testing for these
      genotypes together with the Papanicolaou test did not improve the diagnosis of
      high-grade cervical intraepithelial lesions.

PMID- 22481372
TI  - Components of left ventricular ejection and filling in patients with aortic
      regurgitation assessed by speckle-tracking echocardiography.
AB  - The aim of our study was to evaluate left ventricular (LV) longitudinal, radial,
      and rotational function and its relationship with conventional LV parameters of
      systolic and diastolic function in patients with aortic regurgitation (AR) by
      speckle-tracking echocardiography. MATERIAL AND METHODS. A total of 26
      asymptomatic patients with moderate AR, 34 patients with severe AR, and 28
      healthy controls were included into the study. LV rotation and longitudinal and
      radial strain were measured offline using speckle-tracking imaging. RESULTS. The
      systolic longitudinal strain (-18.3% [SD, 2.18%] vs. -21.0% [SD, 2.52%], P<0.05)
      and strain rate (-1.08 s(-1) [SD, 0.13 s(-1)] vs. -1.27 s(-1) [SD, 0.15 s(-1)],
      P<0.05) were significantly lower and apical rotation (11.3 degrees  [SD, 4.99
      degrees ] vs. 8.30 degrees  [SD, 4.34 degrees ], P<0.05) as well as rotation rate
      (82.72 degrees /s [SD, 28.24  degrees /s] vs. 71.00 degrees /s [SD, 28.04 
      degrees /s], P<0.05) were significantly higher in the patients with moderate AR
      compared with the control patients. The LV systolic basal rotation, systolic
      radial strain, and diastolic radial strain rate were significantly reduced in the
      patients with severe AR compared with the control patients. The global
      longitudinal, radial strain, and LV systolic diameter were the independent
      predictors of LV ejection fraction in the patients with AR (R(2)=0.77). The LV
      systolic basal rotation in the control patients, diastolic longitudinal strain
      rate and systolic longitudinal strain in the patients with moderate and severe
      AR, respectively, were independent predictors of LV diastolic filling.
      CONCLUSIONS. LV long-axis dysfunction with an increased apical rotation was
      present in the patients with moderate AR, while LV radial function and systolic
      basal rotation were found to be reduced in more advanced disease. LV diastolic
      filling depended on diastolic and systolic LV strain and rotation components in
      the patients with AR.

PMID- 22481374
TI  - Zitterbewegung of electrons in quantum wells and dots in the presence of an in
      plane magnetic field.
AB  - We study the effect of an in-plane magnetic field on the zitterbewegung (ZB) of
      electrons in a semiconductor quantum well (QW) and in a quantum dot (QD) with the
      Rashba and Dresselhaus spin-orbit interactions (SOIs). We obtain a general
      expression of the time-evolution of the position vector and current of the
      electron in a semiconductor QW. The amplitude of the oscillatory motion is
      directly related to the Berry connection in momentum space. We find that in
      presence of the magnetic field the ZB in a QW does not vanish when the strengths
      of the Rashba and Dresselhaus SOIs are equal. The in-plane magnetic field helps
      to sustain the ZB in QWs even at a low value of k(0)d (where d is the width of
      the Gaussian wavepacket and k(0) is the initial wavevector). The trembling motion
      of an electron in a semiconductor QW with high Lande g-factor (e.g. InSb) is
      sustained over a long time, even at a low value of k(0)d. Further, we study the
      ZB of an electron in QDs within the two sub-band model numerically. The trembling
      motion persists in time even when the magnetic field is absent as well as when
      the strengths of the SOI are equal. The ZB in QDs is due to the superposition of
      oscillatory motions corresponding to all possible differences of the energy
      eigenvalues of the system. This is an another example of multi-frequency ZB
      phenomenon.

PMID- 22481373
TI  - Short-term roxithromycin treatment attenuates airway inflammation via MAPK/NF
      kappaB activation in a mouse model of allergic asthma.
AB  - OBJECTIVE: We investigated whether roxithromycin reduces ovalbumin-specific
      allergic asthma symptoms in mice, and we further investigated the inhibitory
      mechanism of roxithromycin in ovalbumin-specific allergic asthma. METHODS: Mice
      were divided into five groups (n = 10 for each): control group, roxithromycin
      treated groups (5, 20 and 40 mg/kg) and ovalbumin-challenged group. We measured
      the recruitment of inflammatory cells into the bronchoalveolar lavage fluid
      (BALF) or the lung tissues by Kwik-Diff and hematoxylin and eosin (H&E) staining,
      goblet cell hyperplasia by alcian blue-periodic acid-Schiff (AB-PAS) staining,
      airway hyperresponsiveness (AHR) by whole-body plethysmograph chamber, cytokine
      and immunoglobulin E (IgE) levels by ELISA, and the activation of mitogen
      activated protein (MAP) kinases and nuclear factor-kappa B (NF-kappaB) in the
      lung tissues by Western blotting. RESULTS: Treatment with roxithromycin resulted
      in fewer inflammatory cells in the BALF and peribronchial areas, and decreased
      AHR, goblet cell hyperplasia, IgE levels and inflammatory cytokines, as well as
      MAP kinases and NF-kappaB activation, which are increased in lung tissues of mice
      with ovalbumin-induced allergic asthma. CONCLUSIONS: Our data suggest that oral
      administration of roxithromycin suppresses ovalbumin-induced airway inflammation
      and AHR by regulating the inflammatory cytokines via MAP kinases/NF-kappaB
      pathway in inflammatory cells. Based on these results, we suggest that
      roxithromycin may be used as a therapeutic agent for allergy-induced asthma.

PMID- 22481375
TI  - Value of performing routine postoperative liquid contrast swallow studies
      following robot-assisted Roux-en-Y gastric bypass.
AB  - QUESTIONS UNDER STUDY/PRINCIPLES: In most centers, Upper Gastrointestinal series
      (UGI) following Roux-en-Y Gastric Bypass (RYGB) is performed to rule out GJ
      anastomotic leak. According to the introduction of robotic technology associated
      with a hypothetical decrease of anastomotic complications, we aim to assess the
      validity and cost effectiveness of early routine UGI following robot-assisted
      RYGB. METHODS: Between July 2006 and December 2010, 167 robot-assisted RYGB were
      performed at a single institution. All data were collected prospectively in a
      computerised database and reviewed retrospectively. Patients underwent a
      gastrografin UGI at postoperative day 2 to exclude anastomotic leak or stenosis.
      RESULTS: None of the 167 patients who underwent an early UGI experienced leak
      radiologically and clinically. The only radiological abnormalities were two GJ
      edema (1.2%) and one jejunojenunostomy stenosis (0.6%), all treated
      conservatively with success. The total cost for the 167 UGI was CHF 93,520 (= USD
      96,886). CONCLUSIONS: In most centres, the risk of anastomotic leak has been the
      rationale for obtaining an UGI following RYGB. However, provided low leak rates
      as for our experience with robotic RYGB, the authors show this exam to be
      expensive and of limited value. A decisional algorithm for on demand UGI has been
      developed according to patient's characteristics and is now under validation.

PMID- 22481376
TI  - Temperature shift-induced reactive oxygen species enhanced validamycin A
      production in fermentation of Streptomyces hygroscopicus 5008.
AB  - In order to enhance the production of validamycin A (VAL-A), a widely used
      agricultural antibiotic, a temperature shift strategy was developed in the
      fermentation of Streptomyces hygroscopicus 5008. VAL-A production and the
      transcriptional levels of its structural genes were enhanced in the optimal
      temperature shift condition. The addition of diphenyleneiodonium [DPI, reactive
      oxygen species (ROS) inhibitor] inhibited intracellular ROS level and VAL-A
      production, which indicated that ROS signal might contribute to the enhancement
      of VAL-A production in the temperature shift process. The transcriptional levels
      of stress response sigma factors SigmaB and SigmaH as well as global regulator
      PhoRP were enhanced, which suggested that these regulators might participate in
      the signal pathway. This study developed a useful strategy for VAL-A production.
      It will help to further understand the regulation mechanism of ROS on VAL-A
      synthesis. The involvement of ROS in this process will encourage researchers to
      develop new ROS induction strategies to enhance VAL-A production.

PMID- 22481378
TI  - Optical properties of HgTe colloidal  quantum dots.
AB  - Room temperature photodetection with HgTe colloidal quantum films is reported
      between 2 and 5 MUm for particles of sizes between ~5 and ~12 nm diameter, and
      photodetection extends to 7 MUm at 80 K. The size-tuning of the absorption of
      HgTe colloidal quantum dots, their optical cross section and the infrared
      absorption depth of films are measured. The tuning with radius is empirically
      given by [see formula in text] where R is in nm. The optical cross section of the
      colloidal dots at 415 nm is approximately proportional to their volume and given
      by sigma(Hg)(415) = 2.6 +/- 0.4 10(-17) cm(2)/mercury atom. The size-dependent
      optical cross section at the band edge ~1.5 10(-15) cm(2) is consistent with the
      expected oscillator strength of the quantum dots. The absorption depth of HgTe
      colloidal dot films is short, about 1-2 MUm, which is an advantage for thin film
      devices. These properties agree rather well with the expectation from the k . p
      model. HgTe colloidal quantum dot thin films show a strong tuning with
      temperature with a large positive thermal shift between 0.4 and 0.2 meV K(-1),
      decreasing with decreasing size within the size range studied and this is
      attributed primarily to electron-phonon effects.

PMID- 22481377
TI  - Molecular and physicochemical characterization of hemoglobin from the high
      altitude Taiwanese brown-toothed shrew (Episoriculus fumidus).
AB  - Red-toothed shrews (subfamily Soricinae) exhibit the highest mass-specific rates
      of O2 consumption recorded among eutherian mammals, though surprisingly no data
      appears to be available on the functional characteristics of their hemoglobin
      (Hb). As a first step in addressing this shortcoming, we investigated the O2
      binding characteristics of Taiwanese brown-toothed shrew (Episoriculus fumidus)
      Hb and its temperature and pH dependence in the absence and presence of anionic
      red blood cell effectors. Although comparative data regarding the intrinsic O2
      affinity of other shrew species are currently unavailable, our data suggest that
      the sensitivity of this high-elevation endemic species' Hb to allosteric effector
      molecules is similar to that of the two lowland species of white-toothed
      (crocidurine) shrews examined to date. The efficient exploitation of blood O2
      reserves by E. fumidus appears to be achieved via synergistic modulation of O2
      affinity by Cl- and organic phosphates that moreover dramatically lowers the
      overall enthalpy of oxygenation of their Hb. Oxygen unloading is presumably
      further enhanced by a relatively high Bohr effect (DeltaLog P50/DeltapH = -0.69)
      and marked reduction in the titratable histidine content (predicted low proton
      buffering value) of the component globin chains relative to human HbA. Notably,
      however, the limited data available suggest these latter attributes may be
      widespread among shrews and hence likely are not adaptations to chronic
      altitudinal hypoxia per se.

PMID- 22481379
TI  - Prognostic factors for the work participation of sick-listed unemployed and
      temporary agency workers with psychological problems.
AB  - INTRODUCTION: Among the working population, unemployed and temporary agency
      workers are a particularly vulnerable group, at risk for sickness absence due to
      psychological problems. Knowledge of prognostic factors for work participation
      could help identify sick-listed workers with a high-risk for work disability and
      provide input for sickness absence counseling. The purpose of this study was to
      identify prognostic factors for the work participation of medium- and long-term
      sick-listed unemployed and temporary agency workers with psychological problems.
      METHODS: A cohort of 932 sick-listed unemployed and temporary agency workers with
      psychological problems was followed for one and a half years. Data collection was
      conducted at three time-frames: 10 months, 18 months and 27 months after
      reporting sick. Univariate and multiple logistic regression analyses were
      performed. RESULTS: Perceived health, full return-to-work (RTW) expectations, age
      and work status at 18 months were strong prognostic factors for work
      participation at subsequent time-frames in the univariate analyses. Multiple
      logistic regression revealed that full RTW expectation was a prognostic factor
      for future work participation in both the medium- and long-term, whereas moderate
      to-good perceived health was a prognostic factor for work participation in the
      medium-term. Being under 45 years of age and having a positive work status at 18
      months were prognostic factors for work participation in the long-term.
      CONCLUSIONS: Workers' self-appraisal of health, age and work status were strong
      prognostic factors for the future work participation of sick-listed unemployed
      and temporary agency workers with psychological problems. These findings could
      help occupational and insurance physicians identify high-risk sick-listed workers
      for sickness absence counseling.

PMID- 22481380
TI  - Hyphenated techniques as tools for speciation analysis of metal-based
      pharmaceuticals: developments and applications.
AB  - Method development and applications of hyphenated techniques as tools for
      speciation analysis of metal-based pharmaceuticals are summarized within this
      review. Advantages and limitations of the separation modes-high-performance
      liquid chromatography (HPLC), capillary electrophoresis (CE), and gas
      chromatography (GC)-as well as the detection modes-inductively coupled plasma
      mass spectrometry (ICP-MS) and electrospray ionization-mass spectrometry (ESI-MS)
      are discussed. ICP-MS detection is found to be advantageous for the
      quantification of drugs containing metals and other heteroatoms. The species
      independent sensitivity and multielement capabilities of ICP-MS allow it to be
      used for quantification even when species-specific standards are not available,
      as well as to determine the stoichiometry in metallodrug-biomolecule
      interactions. Molecular information that is totally destroyed when ICP is applied
      as ionization source and is therefore not obtainable via ICP-MS detection can be
      accessed by the complementary technique of ESI-MS. Speciation analysis combining
      both elemental and molecular information is therefore a powerful tool for the
      analysis of metal-based pharmaceuticals and their metabolites in body fluids and
      other relevant matrices.

PMID- 22481381
TI  - Direct measurement of Criegee intermediate (CH2OO) reactions with acetone,
      acetaldehyde, and hexafluoroacetone.
AB  - Criegee biradicals, i.e., carbonyl oxides, are critical intermediates in
      ozonolysis and have been implicated in autoignition chemistry and other
      hydrocarbon oxidation systems, but until recently the direct measurement of their
      gas-phase kinetics has not been feasible. Indirect determinations of Criegee
      intermediate kinetics often rely on the introduction of a scavenger molecule into
      an ozonolysis system and analysis of the effects of the scavenger on yields of
      products associated with Criegee intermediate reactions. Carbonyl species, in
      particular hexafluoroacetone (CF(3)COCF(3)), have often been used as scavengers.
      In this work, the reactions of the simplest Criegee intermediate, CH(2)OO
      (formaldehyde oxide), with three carbonyl species have been measured by laser
      photolysis/tunable synchrotron photoionization mass spectrometry. Diiodomethane
      photolysis produces CH(2)I radicals, which react with O(2) to yield CH(2)OO + I.
      The formaldehyde oxide is reacted with a large excess of a carbonyl reactant and
      both the disappearance of CH(2)OO and the formation of reaction products are
      monitored. The rate coefficient for CH(2)OO + hexafluoroacetone is k(1) = (3.0 +/
      0.3) * 10(-11) cm(3) molecule(-1) s(-1), supporting the use of hexafluoroacetone
      as a Criegee-intermediate scavenger. The reactions with acetaldehyde, k(2) = (9.5
      +/- 0.7) * 10(-13) cm(3) molecule(-1) s(-1), and with acetone, k(3) = (2.3 +/-
      0.3) * 10(-13) cm(3) molecule(-1) s(-1), are substantially slower. Secondary
      ozonides and products of ozonide isomerization are observed from the reactions of
      CH(2)OO with acetone and hexafluoroacetone. Their photoionization spectra are
      interpreted with the aid of quantum-chemical and Franck-Condon-factor
      calculations. No secondary ozonide was observable in the reaction of CH(2)OO with
      acetaldehyde, but acetic acid was identified as a product under the conditions
      used (4 Torr and 293 K).

PMID- 22481383
TI  - Platinum-nanoparticle-supported core--shell polymer nanospheres with unexpected
      water stability and facile further modification.
AB  - Core-shell nanospheres (CSNSs) with hydrophobic cores and hydrophilic shells were
      fabricated via a simple mini-emulsion polymerization for the stabilization of
      platinum nanoparticles (Pt-NPs). The CSNSs showed extremely high loading capacity
      of Pt-NPs (the largest loading amount of the Pt-NPs was about 49.2 wt%).
      Importantly, the Pt-NPs/CSNSs nanocomposites had unexpected stability in aqueous
      solution. DLS results revealed that the CSNSs loaded with Pt-NPs exhibited almost
      no aggregation after standing for a long time . However, the Pt-NPs immobilized
      on the CSNSs were not straitlaced: they could transport and redistribute between
      CSNSs freely when the environmental temperature was higher than the melting point
      of the CSNS shell. Owing to their excellent stability in aqueous solution, the
      surface of the Pt-NPs/CSNSs nanocomposites could be further decorated easily. For
      example, polyaniline (PANI)-coated Pt-NPs/CSNSs, nickel (Ni)-coated Pt-NPs/CSNSs
      and PANI/Pt-NPs dual-layer hollow nanospheres were facilely fabricated from the
      Pt-NPs/CSNS nanocomposites.

PMID- 22481382
TI  - Volume estimation of the thalamus using freesurfer and stereology: consistency
      between methods.
AB  - Freely available automated MR image analysis techniques are being increasingly
      used to investigate neuroanatomical abnormalities in patients with neurological
      disorders. It is important to assess the specificity and validity of automated
      measurements of structure volumes with respect to reliable manual methods that
      rely on human anatomical expertise. The thalamus is widely investigated in many
      neurological and neuropsychiatric disorders using MRI, but thalamic volumes are
      notoriously difficult to quantify given the poor between-tissue contrast at the
      thalamic gray-white matter interface. In the present study we investigated the
      reliability of automatically determined thalamic volume measurements obtained
      using FreeSurfer software with respect to a manual stereological technique on 3D
      T1-weighted MR images obtained from a 3 T MR system. Further to demonstrating
      impressive consistency between stereological and FreeSurfer volume estimates of
      the thalamus in healthy subjects and neurological patients, we demonstrate that
      the extent of agreeability between stereology and FreeSurfer is equal to the
      agreeability between two human anatomists estimating thalamic volume using
      stereological methods. Using patients with juvenile myoclonic epilepsy as a model
      for thalamic atrophy, we also show that both automated and manual methods provide
      very similar ratios of thalamic volume loss in patients. This work promotes the
      use of FreeSurfer for reliable estimation of global volume in healthy and
      diseased thalami.

PMID- 22481385
TI  - A marriage of convenience.

PMID- 22481386
TI  - Four-strain flu vaccines coming to a pharmacy near you.

PMID- 22481384
TI  - Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia.
AB  - BACKGROUND: Recessive LPIN1 mutations were identified as a cause of severe
      rhabdomyolysis in pediatric patients. The human lipin family includes two other
      closely related members, lipin-2 and 3, which share strong homology and similar
      activity. The study aimed to determine the involvement of the LPIN family genes
      in a cohort of pediatric and adult patients (n = 171) presenting with muscular
      symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L)
      rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the
      clinical findings in patients harboring mutations. METHODS: Coding regions of
      LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs.
      RESULTS: Eighteen patients harbored two LPIN1 mutations, including a frequent
      intragenic deletion. All presented with severe episodes of rhabdomyolysis,
      starting before age 6 years except two (8 and 42 years). Few patients also
      suffered from permanent muscle symptoms, including the eldest ones (>= 40 years).
      Around 3/4 of muscle biopsies showed accumulation of lipid droplets. At least 40%
      of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in
      LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or
      myalgia). These variants were non-functional in yeast complementation assay based
      on respiratory activity, except the LPIN3-P24L variant. CONCLUSION: LPIN1-related
      myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally
      in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No
      major defects of LPIN2 or LPIN3 genes were associated with muscular
      manifestations.

PMID- 22481387
TI  - Panel backs pain drug studies with new safety checks.

PMID- 22481388
TI  - HIV researchers show virus the door.

PMID- 22481389
TI  - Companies hope for rare win with cancer stem cell therapies.

PMID- 22481390
TI  - Battle looms over regulatory classification of complex drugs.

PMID- 22481391
TI  - Microfluidic chips promise better diagnosis for sickle cell disease.

PMID- 22481393
TI  - With a slip under the tongue, allergy tablets subdue the sniffles.

PMID- 22481396
TI  - Vaccines shoot for more precise population targets.

PMID- 22481397
TI  - Straight talk with...David Kaslow. Interviewed by Roxanne Khamsi.

PMID- 22481399
TI  - Remembered for forgetting.

PMID- 22481400
TI  - Cockamamie state laws threaten genetic rights.

PMID- 22481402
TI  - Basophils from humans with systemic lupus erythematosus do not express MHC-II.

PMID- 22481404
TI  - Vitamin E: good for the heart, bad for the bones?

PMID- 22481405
TI  - Breathe easy: microbes protect from allergies.

PMID- 22481406
TI  - In cancer drug resistance, germline matters too.

PMID- 22481407
TI  - Hypothalamic BDNF and obesity: found in translation.

PMID- 22481408
TI  - Neighborhood watch orchestrates liver regeneration.

PMID- 22481410
TI  - Getting to the core of addiction: hatching the addiction egg.

PMID- 22481411
TI  - Getting to the core of addiction: Hooking CB2 receptor into drug abuse?

PMID- 22481421
TI  - Community-based treatment of serious bacterial infections in newborns and young
      infants: a randomized controlled trial assessing three antibiotic regimens.
AB  - BACKGROUND: Sepsis in the neonatal period is a major cause of child mortality in
      low-income countries. Hospitalization and parenteral penicillin/ampicillin and
      gentamicin therapy are recommended for management. Many families, however, are
      unable to access hospital care, and most home-delivered newborns who develop
      sepsis die without receiving antibiotic therapy. Appropriate community-based
      therapy in such situations is undefined. We compared failure rates of 3 clinic
      based antibiotic regimens in 0- to 59-day-old infants with possible serious
      bacterial infection whose families refused hospitalization in Karachi communities
      with high neonatal mortality rates>45/1000 live births. METHODS: Eligible infants
      were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg
      once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM)
      reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim
      sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gentamicin IM
      OD. Primary outcome was treatment failure, defined as death, deterioration in
      clinical condition during therapy or no improvement after 2 days. RESULTS:
      Possible serious bacterial infection was diagnosed in 704 infants, among 5766
      screened. Among 434 (61.6%) randomized to clinic-based therapy, there were 13 of
      145 failures with penicillin-gentamicin, 22 of 145 with ceftriaxone and 26 of 143
      with TMP-SMX-gentamicin. Treatment failure was significantly higher with TMP-SMX
      gentamicin compared with penicillin-gentamicin [relative risk 2.03, 95%
      confidence interval: 1.09-3.79] by intention-to-treat analysis. Differences were
      not significant in the ceftriaxone versus penicillin-gentamicin comparison
      [relative risk 1.69, 95% confidence interval 0.89-3.23). By 14 days, there were 2
      deaths in the penicillin-gentamicin group, 3 in the ceftriaxone group and 11 in
      the TMP-SMX-gentamicin group [relative risk 5.58, 95% confidence interval: 1.26
      24.72 (group 3 versus 1)]. CONCLUSION: When hospitalization of sick infants is
      unfeasible, outpatient therapy with injectable antibiotics is an effective
      option. Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin.
      Ceftriaxone is a more expensive option, and may be less effective, although this
      requires further research.

PMID- 22481422
TI  - Neutrophil CD64 as a diagnostic marker in neonatal sepsis.
AB  - We assessed neutrophil CD64 as a diagnostic marker for neonatal sepsis. For early
      onset sepsis, the CD64 index with a cut-point value of 2.38 had sensitivity,
      specificity and negative predictive values of 100%, 68% and 100%, respectively.
      For late-onset sepsis, the respective values were 3.62, 75%, 77% and 96%.
      Neutrophil CD64 index can be incorporated as a valuable marker for excluding
      neonatal sepsis.

PMID- 22481418
TI  - Cystic fibrosis: a mucosal immunodeficiency syndrome.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel
      that regulates the transport of ions and the movement of water across the
      epithelial barrier. Mutations in CFTR, which form the basis for the clinical
      manifestations of cystic fibrosis, affect the epithelial innate immune function
      in the lung, resulting in exaggerated and ineffective airway inflammation that
      fails to eradicate pulmonary pathogens. Compounding the effects of excessive
      neutrophil recruitment, the mutant CFTR channel does not transport antioxidants
      to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR
      expression in leukocytes outside of the lung does not markedly impair their
      function, the expected regulation of inflammation in the airways is clearly
      deficient in cystic fibrosis. The resulting bacterial infections, which are
      caused by organisms that have substantial genetic and metabolic flexibility, can
      resist multiple classes of antibiotics and evade phagocytic clearance. The
      development of animal models that approximate the human pulmonary phenotypes
      airway inflammation and spontaneous infection-may provide the much-needed tools
      to establish how CFTR regulates mucosal immunity and to test directly the effect
      of pharmacologic potentiation and correction of mutant CFTR function on bacterial
      clearance.

PMID- 22481423
TI  - Prevalence of and risk factors for human rhinovirus infection in healthy
      aboriginal and non-aboriginal Western Australian children.
AB  - BACKGROUND: Human rhinovirus (HRV) species C (HRV-C) have been associated with
      frequent and severe acute lower respiratory infections and asthma in hospitalized
      children. The prevalence of HRV-C among healthy children and whether this varies
      with ethnicity is unknown. OBJECTIVE: To describe the prevalence of HRV species
      and their associations with demographic, environmental and socioeconomic factors
      in healthy Aboriginal and non-Aboriginal children. METHODS: Respiratory viruses
      and bacteria were identified in 1006 nasopharyngeal aspirates collected from a
      cohort of 79 Aboriginal and 88 non-Aboriginal Western Australian children before
      2 years of age. HRV-positive nasopharyngeal aspirates were typed for HRV species
      and genotypes. Longitudinal growth models incorporating generalized estimating
      equations were used to investigate associations between HRV species and potential
      risk factors. RESULTS: Of the 159 typed specimens, we identified 83 (52.2%) human
      rhinovirus species A (HRV-A), 26 (16.4%), human rhinovirus species B and 50
      (31.4%) HRV-C. HRV-C was associated with upper respiratory symptoms in Aboriginal
      (odds ratio, 3.77; 95% confidence interval:1.05-13.55) and non-Aboriginal
      children (odds ratio, 5.85; 95% confidence interval: 2.33-14.66). HRV-A and HRV-C
      were associated with carriage of respiratory bacteria. In Aboriginal children,
      HRV-A was more common in the summer and in those whose mothers were employed
      prior to delivery. In non-Aboriginal children, day-care attendance and exclusive
      breast-feeding at age 6-8 weeks were associated with detection of HRV-A, and
      gestational smoking with detection of HRV-C. CONCLUSIONS: Factors associated with
      the presence of HRV differ between Aboriginal and non-Aboriginal children. In
      contrast to HRV-A, HRV-C is associated with upper respiratory symptoms suggesting
      that HRV-C is likely to be implicated in respiratory illness.

PMID- 22481424
TI  - Retropharyngeal abscess in children: the rising incidence of methicillin
      resistant Staphylococcus aureus.
AB  - BACKGROUND: Because of a recent upsurge in retropharyngeal abscess (RPA) cases
      due to community-associated methicillin-resistant Staphylococcus aureus (MRSA),
      we reevaluated the microbiology, clinical manifestations and treatment outcome of
      RPA over the past 6 years (2004 to 2010). Findings were compared with those of a
      previous 11-year study (1993 to 2003) period. METHODS: A retrospective review of
      medical records of children with RPA. RESULTS: One hundred fourteen children (61
      males) with RPA were identified representing a 2.8-fold increase in incidence
      (per 10,000 admissions) over the previous 11-year period. Abscess drainage was
      performed in 74 (65%). A total of 116 isolates (93 aerobes, 23 anaerobes) were
      recovered from 66 specimens. S. aureus was recovered from 25 (38%) of the 66
      specimens compared with 2 (4.9%) of 41 in the previous 11 years; 16 (64%) of 25
      were MRSA compared with none in the previous 11 years. Children whose abscess
      grew MRSA were younger (mean 11 months) than the others (mean 62 months)
      (P<0.001) and required longer duration of hospitalization (mean 8.8 days) than
      the rest (mean 4.5 days) (P=0.002). Five children had mediastinitis; all caused
      by MRSA. All MRSA isolates were susceptible to clindamycin. Ceftriaxone plus
      clindamycin was the most common treatment regimen. All patients had resolution of
      their abscesses. CONCLUSIONS: RPA has increased in frequency in our pediatric
      population with an associated increase of Staphylococcus aureus, mainly community
      associated MRSA. This is likely due to the overall increase in community
      associated MRSA infections in our pediatric patients. Treatment with ceftriaxone
      and clindamycin in addition to surgical drainage was effective.

PMID- 22481425
TI  - Childhood influenza in the outpatient setting in Shanghai, China.
AB  - BACKGROUND: Influenza is a common cause of outpatient visits in childhood.
      Influenza vaccine has been widely used for children >= 6 months of age in
      developed countries based on accumulating evidence on the substantial
      socioeconomic burden of influenza in children. However, the data of childhood
      influenza in China are scarce. METHODS: We carried out a prospective surveillance
      of influenza among children visiting outpatient clinic for influenza-like illness
      between June 2009 and May 2011. Respiratory samples were obtained from the
      enrolled cases and the demographic and clinical data were collected. RESULTS: Of
      2356 enrolled cases, influenza was virologically confirmed in 608 (25.81%)
      otherwise healthy children. Four hundred sixty-eight (76.97%) were influenza A
      positive (A/H3N2:236, pandemic A/H1N1:219, seasonal A/H1N1:4, A/H3N2 coinfected
      with pandemic A/H1N1:3, untyped:6) and 142 (23.35%) were influenza B positive (2
      coinfected with pandemic A/H1N1). The outbreaks of A/H3N2, pandemic A/H1N1 and
      influenza B took place in fall, winter and spring, alternatively. More
      institutionalized children were affected when the outbreaks overlapped with
      school opening. Among 603 children with a single influenza virus infection, 289
      (47.93%) were <3 years old and 283 (46.93%) had close contact with persons who
      had fever or respiratory infection, of whom, 192 (67.84%) contacts were family
      members. CONCLUSION: The annual outbreak of influenza led to a high rate of
      outpatient visits among children in Shanghai. Outbreaks occurred in younger and
      institutionalized children. Household members were the main disseminators to
      spread influenza among children.

PMID- 22481426
TI  - Use of pentoxifylline in treatment of children with dengue hemorrhagic fever.
AB  - The current treatment for dengue hemorrhagic fever largely consists of supportive
      care. The drug pentoxifylline has been shown to blunt the proinflammatory actions
      of tumor necrosis factor-alpha, a key mediator of dengue hemorrhagic fever. We
      performed a pilot study evaluating pentoxifylline's effect on 55 children with
      dengue hemorrhagic fever. We believe our findings support the existing literature
      on its potential use in severe infection.

PMID- 22481427
TI  - Dose-range study of MF59-adjuvanted versus nonadjuvanted monovalent A/H1N1
      pandemic influenza vaccine in six- to less than thirty-six-month-old children.
AB  - BACKGROUND: The successful vaccination of children 6 to 36 months of age against
      2009 A/H1N1 influenza was essential to help reduce the burden of pandemic disease
      in both the pediatric and adult populations. OBJECTIVES: We compared the
      immunogenicity and safety of 4 alternative monovalent vaccine formulations to
      identify which provided optimal levels of seroprotection according to the US and
      European Union (EU) licensure criteria. SUBJECTS AND METHODS: A total of 654
      healthy subjects (6 to <36 months old) were given 2 vaccine doses 3 weeks apart.
      Participants were assigned to 1 of the 4 immunization groups, receiving MF59
      adjuvanted (Novartis Vaccines, Marburg, Germany) vaccine either containing 3.75
      MUg or 7.5 MUg of A/H1N1 California/7/2009 antigen, or nonadjuvanted vaccine
      containing 7.5 MUg or 15 MUg of antigen. Antibody titers were assessed by
      hemagglutination inhibition assay 3 weeks, 3 months and 1 year after
      immunization. Vaccine safety was monitored throughout the study. RESULTS: After 1
      dose, both adjuvanted formulations met the US and EU criteria for seroconversion;
      the 15 MUg nonadjuvanted vaccine met the EU criterion for seroconversion alone.
      The US and EU criteria for seroprotection were only met by adjuvanted groups.
      MF59-adjuvanted formulations alone resulted in clinically significant persisting
      antibody titers after 12 months. All vaccines were well tolerated. CONCLUSIONS: A
      single dose of MF59-adjuvanted vaccine containing 3.75 MUg A/H1N1 antigen was
      highly immunogenic, met both the US and EU licensure criteria and was well
      tolerated. These data support the suitability of this monovalent vaccine
      formulation for pandemic use in children 6 to <36 months of age.

PMID- 22481428
TI  - Factors associated with loss of penicillin G concentrations in serum after
      intramuscular benzathine penicillin G injection: a meta-analysis.
AB  - BACKGROUND: An interval of 3-4 weeks between intramuscular injections of 1.2
      million units of benzathine penicillin G as prophylaxis against group A
      streptococcal infection is recommended by health organizations for patients with
      pediatric rheumatic fever and heart disease. METHODS: We reviewed the literature
      for evidence of the persistence of serum penicillin G during the first 4 weeks
      after the recommended dose of benzathine penicillin G. RESULTS: The weighted-mean
      concentration was <0.02 ug/mL by 3 weeks after the initial dose. Weighted means
      were lower in studies done after 1990 than before (P<0.01), in studies dealing
      with secondary versus primary prophylaxis (P<0.01) and in studies in children
      versus those in adults (P<0.02). CONCLUSIONS: Recommendations for benzathine
      penicillin G prophylaxis may need reevaluation.

PMID- 22481429
TI  - Foreign adopted children are a source of methicillin-resistant Staphylococcus
      aureus transmission to countries with low prevalence.
AB  - We report a 13.0% prevalence rate of methicillin-resistant Staphylococcus aureus
      (MRSA) carriers in foreign adopted children, who are frequently hospitalized
      within the first year after arrival. Hospitalization in the country of origin and
      special need status are no significant risk factors for MRSA colonization.
      Healthcare workers are overrepresented among their adoptive parents. These
      children represent a potential source of MRSA transmission into the healthcare
      system.

PMID- 22481430
TI  - Large-scale parallel arrays of silicon nanowires via block copolymer directed
      self-assembly.
AB  - Extending the resolution and spatial proximity of lithographic patterning below
      critical dimensions of 20 nm remains a key challenge with very-large-scale
      integration, especially if the persistent scaling of silicon electronic devices
      is sustained. One approach, which relies upon the directed self-assembly of block
      copolymers by chemical-epitaxy, is capable of achieving high density 1 : 1
      patterning with critical dimensions approaching 5 nm. Herein, we outline an
      integration-favourable strategy for fabricating high areal density arrays of
      aligned silicon nanowires by directed self-assembly of a PS-b-PMMA block
      copolymer nanopatterns with a L(0) (pitch) of 42 nm, on chemically pre-patterned
      surfaces. Parallel arrays (5 * 10(6) wires per cm) of uni-directional and
      isolated silicon nanowires on insulator substrates with critical dimension
      ranging from 15 to 19 nm were fabricated by using precision plasma etch
      processes; with each stage monitored by electron microscopy. This step-by-step
      approach provides detailed information on interfacial oxide formation at the
      device silicon layer, the polystyrene profile during plasma etching, final
      critical dimension uniformity and line edge roughness variation nanowire during
      processing. The resulting silicon-nanowire array devices exhibit Schottky-type
      behaviour and a clear field-effect. The measured values for resistivity and
      specific contact resistance were ((2.6 +/- 1.2) * 10(5)Omegacm) and ((240 +/- 80)
      Omegacm(2)) respectively. These values are typical for intrinsic (un-doped)
      silicon when contacted by high work function metal albeit counterintuitive as the
      resistivity of the starting wafer (~10 Omegacm) is 4 orders of magnitude lower.
      In essence, the nanowires are so small and consist of so few atoms, that
      statistically, at the original doping level each nanowire contains less than a
      single dopant atom and consequently exhibits the electrical behaviour of the un
      doped host material. Moreover this indicates that the processing successfully
      avoided unintentional doping. Therefore our approach permits tuning of the device
      steps to contact the nanowires functionality through careful selection of the
      initial bulk starting material and/or by means of post processing steps e.g.
      thermal annealing of metal contacts to produce high performance devices. We
      envision that such a controllable process, combined with the precision patterning
      of the aligned block copolymer nanopatterns, could prolong the scaling of
      nanoelectronics and potentially enable the fabrication of dense, parallel arrays
      of multi-gate field effect transistors.

PMID- 22481431
TI  - Confusion of Mobius aromaticity: disruption of annulenic pathway in singly N
      confused [28]hexaphyrin and its mono-Pd(II) complex.
AB  - Singly N-confused [26] and [28]hexaphyrins (4, 5) with planar and twisted
      structures, respectively, were prepared via the acid catalyzed [3 + 3]
      condensation of N-confused and regular tripyrrane precursors. Huckel aromaticity
      is observed for [26]hexaphyrin, while the [28]hexaphyrin and its mono-Pd(II)
      complex exhibit "nonaromaticity" in spite of their Mobius-type structures,
      judging from the spectroscopic features and theoretical calculations.

PMID- 22481433
TI  - Origin of magnetic interactions and their influence on the structural properties
      of Ni2MnGa and related compounds.
AB  - In this work, we perform first-principles DFT calculations to investigate the
      interplay between magnetic and structural properties in Ni(2)MnGa. We demonstrate
      that the relative stability of austenite (cubic) and non-modulated martensite
      (tetragonal) phases depends critically on the magnetic interactions between Mn
      atoms. While standard approximate DFT functionals stabilize the latter phase, a
      more accurate treatment of electronic localization and magnetism, obtained with
      DFT+U, suppresses the non-modulated tetragonal structure for the stoichiometric
      compound, in better agreement with experiments. We show that the Anderson
      impurity model, with Mn atoms treated as magnetic impurities, can explain this
      observation and that the fine balance between super-exchange RKKY type
      interactions mediated by Ni d and Ga p orbitals determines the equilibrium
      structure of the crystal. The Anderson model is also demonstrated to capture the
      effect of the number of valence electrons per unit cell on the structural
      properties, often used as an empirical parameter to tune the behavior of
      Ni(2)MnGa based alloys. Finally, we show that off-stoichiometric compositions
      with excess Mn promote transitions to a non-modulated tetragonal structure, in
      agreement with experiments.

PMID- 22481432
TI  - Antiangiogenic agents in the management of non-small cell lung cancer: where do
      we stand now and where are we headed?
AB  - Several therapies targeting angiogenesis are currently in development for non
      small cell lung cancer (NSCLC). This review discusses results of recent clinical
      trials evaluating chemotherapy plus antiangiogenic therapy for NSCLC.
      Bevacizumab, an anti-VEGF antibody, is currently approved for the treatment of
      advanced NSCLC in combination with carboplatin and paclitaxel. Completed phase
      III trials evaluating bevacizumab plus chemotherapy have shown prolonged
      progression-free survival; however, not all trials showed significant improvement
      in overall survival (OS). Phase III trials of the tyrosine kinase inhibitors
      (TKIs) vandetanib and sorafenib and the vascular disrupting agent ASA404 also
      failed to improve OS compared with chemotherapy alone. Clinical trials are
      ongoing involving several new antiangiogenic therapies, including ramucirumab,
      aflibercept, cediranib, BIBF 1120, sunitinib, pazopanib, brivanib, ABT-869,
      axitinib, ABT-751, and NPI-2358; several of these agents have shown promising
      phase I/II results. Results from recently completed and ongoing phase III trials
      will determine if these newer antiangiogenic agents will be incorporated into
      clinical practice.

PMID- 22481434
TI  - [Abstracts of the 78th Annual Meeting of the German Society for Cardiology-Heart
      and Circulation Research. April 11-14, 2012. Mannheim, Germany].

PMID- 22481435
TI  - Memory on the move.

PMID- 22481436
TI  - Memory CD4+ T cells: fate determination, positive feedback and plasticity.
AB  - Naive CD4(+) T cells undergo massive cell proliferation upon encountering their
      cognate ligand. This proliferation depends upon appropriate cues from the antigen
      presenting cells that have processed the antigen and present the peptide to the T
      cells, and requires the establishment of a cytokine environment that can support
      such proliferation. Expansion of antigen-specific CD4(+) T cells needs to be
      coupled with differentiation into one of several effector/regulatory phenotypes
      if the priming event is to result in cells that can initially act to control the
      particular pathogen that elicited the response, and later to serve as memory
      cells to insure an appropriate response upon reintroduction of the pathogen.
      Here, we discuss the initiation of T helper lineage commitment, the positive
      feedback regulation by the cytokine environment to enhance and stabilize the
      differentiation into distinct T helper subsets, and the biological significance
      of CD4(+) T cell plasticity and long-term CD4(+) T cell memory.

PMID- 22481437
TI  - IgM memory B cells: a mouse/human paradox.
AB  - Humoral memory is maintained by two types of persistent cells, memory B cells and
      plasma cells, which have different phenotypes and functions. Long-lived plasma
      cells can survive for a lifespan within a complex niche in the bone marrow and
      provide continuous protective serum antibody levels. Memory B cells reside in
      secondary lymphoid organs, where they can be rapidly mobilized upon a new
      antigenic encounter. Surface IgG has long been taken as a surrogate marker for
      memory in the mouse. Recently, however, we have brought evidence for a long-lived
      IgM memory B cell population in the mouse, while we have also argued that, in
      humans, these same cells are not classical memory B cells but marginal zone (MZ)
      B cells which, as opposed to their mouse MZ counterpart, recirculate and carry a
      mutated B cell receptor. In this review, we will discuss these apparently
      paradoxical results.

PMID- 22481438
TI  - Immunological memory ? protective immunity.
AB  - So-called 'immunological memory' is, in my view, a typical example where a field
      of enquiry, i.e. to understand long-term protection to survive reexposure to
      infection, has been overtaken by 'l'art pour l'art' of 'basic immunology'. The
      aim of this critical review is to point out some key differences between academic
      text book-defined immunological memory and protective immunity as viewed from a
      co-evolutionary point of view, both from the host and the infectious agents. A
      key conclusion is that 'immunological memory' of course exists, but only in
      particular experimental laboratory models measuring 'quicker and better'
      responses after an earlier immunization. These often do correlate with, but are
      not the key mechanisms of, protection. Protection depends on pre-existing
      neutralizing antibodies or pre-activated T cells at the time of infection-as
      documented by the importance of maternal antibodies around birth for survival of
      the offspring. Importantly, both high levels of antibodies and of activated T
      cells are antigen driven. This conclusion has serious implications for our
      thinking about vaccines and maintaining a level of protection in the population
      to deal with old and new infectious diseases.

PMID- 22481439
TI  - How to halve ploidy: lessons from budding yeast meiosis.
AB  - Maintenance of ploidy in sexually reproducing organisms requires a specialized
      form of cell division called meiosis that generates genetically diverse haploid
      gametes from diploid germ cells. Meiotic cells halve their ploidy by undergoing
      two rounds of nuclear division (meiosis I and II) after a single round of DNA
      replication. Research in Saccharomyces cerevisiae (budding yeast) has shown that
      four major deviations from the mitotic cell cycle during meiosis are essential
      for halving ploidy. The deviations are (1) formation of a link between homologous
      chromosomes by crossover, (2) monopolar attachment of sister kinetochores during
      meiosis I, (3) protection of centromeric cohesion during meiosis I, and (4)
      suppression of DNA replication following exit from meiosis I. In this review we
      present the current understanding of the above four processes in budding yeast
      and examine the possible conservation of molecular mechanisms from yeast to
      humans.

PMID- 22481442
TI  - Selection of prophylactic antibiotics according to the microorganisms isolated
      from surgical site infections (SSIs) in a previous series of surgeries reduces
      SSI incidence after pancreaticoduodenectomy.
AB  - BACKGROUND: The incidence of surgical site infections (SSIs) is high after
      pancreaticoduodenectomy (PD). METHODS: We divided 116 consecutive patients who
      underwent PD into an early group (n = 58) and a later group (n = 58) according to
      time of surgery. In both groups, endoscopic retrograde biliary drainage was
      mainly employed for the patients with obstructive jaundice. In the later group,
      prophylactic antibiotics were selected according to the susceptibility of
      microorganisms isolated from SSIs in the early group. The incidence of SSIs was
      compared between the groups. RESULTS: The background characteristics (including
      methods of preoperative biliary drainage and microorganisms in the bile obtained
      before or during operation) of the patients were not significantly different
      between the groups, except for the serum albumin level, which was lower in the
      later group than in the early group (P = 0.0026). The incidence of SSIs was
      significantly lower in the later group (24.1 %) than in the early group (46.6 %)
      (P = 0.0116). Belonging to the later group was one independent negative risk
      factor for SSI. CONCLUSIONS: Selection of prophylactic antibiotics on the basis
      of microorganisms isolated from SSIs in the early group contributed to the
      reduced incidence of SSIs in the later group after PD.

PMID- 22481440
TI  - PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling.
AB  - The secreted protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds
      to low-density lipid (LDL) receptor family members LDLR, very low density
      lipoprotein receptor (VLDLR) and apolipoprotein receptor 2 (ApoER2), and promotes
      their degradation in intracellular acidic compartments. In the liver, LDLR is a
      major controller of blood LDL levels, whereas VLDLR and ApoER2 in the brain
      mediate Reelin signaling, a critical pathway for proper development of the
      nervous system. Expression level of PCSK9 in the brain is highest in the
      cerebellum during perinatal development, but is also increased in the adult brain
      after ischemia. The mechanism of PCSK9 function and its involvement in neuronal
      apoptosis is poorly understood. We show here that RNAi-mediated knockdown of
      PCSK9 significantly reduced the death of potassium-deprived cerebellar granule
      neurons (CGN), as shown by reduced levels of nuclear phosphorylated c-Jun and
      activated caspase-3, as well as condensed apoptotic nuclei. ApoER2 protein levels
      were increased in PCSK9 RNAi cells. Knockdown of ApoER2 but not of VLDLR was
      sufficient to reverse the protection provided by PCSK9 RNAi, suggesting that
      proapoptotic signaling of PCSK9 is mediated by altered ApoER2 function.
      Pharmacological inhibition of signaling pathways associated with lipoprotein
      receptors suggested that PCSK9 regulates neuronal apoptosis independently of NMDA
      receptor function but in concert with ERK and JNK signaling pathways. PCSK9 RNAi
      also reduced staurosporine-induced CGN apoptosis and axonal degeneration in the
      nerve growth factor-deprived dorsal root ganglion neurons. We conclude that PCSK9
      potentiates neuronal apoptosis via modulation of ApoER2 levels and related anti
      apoptotic signaling pathways.

PMID- 22481443
TI  - Faecal calprotectin -- a useful tool in the management of inflammatory bowel
      disease.
AB  - Inflammatory bowel disease (IBD) should be suspected in any patient presenting
      with chronic or recurrent abdominal pain and diarrhoea. Current guidelines
      suggest performing invasive endoscopy with histological sampling for further
      diagnosis. Measuring calprotectin, a neutrophilic protein, in faeces has been
      proposed as a surrogate marker of intestinal inflammation. Calprotectin values
      have been shown to reliably differentiate between IBD and non-organic disease in
      symptomatic patients and, when elevated, warrant early endoscopic investigation
      to rule out IBD and other organic pathologies. Endoscopy with histological
      sampling is also used to evaluate disease activity and here, too, faecal
      calprotectin values seem to correlate well. In a number of studies, faecal
      calprotectin values have consistently shown to better assess mucosal inflammation
      than clinical indices and serum markers. Calprotectin's advantage of non-invasive
      monitoring of disease activity is especially beneficial when considering the
      dynamics of repeated measurements. Mucosal healing (MH) has been associated with
      sustained clinical remission, reduced rates of hospitalisation and of surgical
      resection, both in Crohn's disease and ulcerative colitis patients. Elevated
      faecal calprotectin levels in patients in clinical remission are associated with
      increased risk of disease relapse within 12 months follow-up. In most clinically
      quiescent IBD, residual mucosal inflammation is still present; it appears that
      faecal calprotectin can detect subclinical mucosal inflammation and thus might
      identify patients at risk for relapse.  In summary, measuring faecal calprotectin
      can be highly useful in the diagnosis and disease management of patients with IBD
      and could help predict disease course.

PMID- 22481441
TI  - Primary cilia elongation in response to interleukin-1 mediates the inflammatory
      response.
AB  - Primary cilia are singular, cytoskeletal organelles present in the majority of
      mammalian cell types where they function as coordinating centres for
      mechanotransduction, Wnt and hedgehog signalling. The length of the primary
      cilium is proposed to modulate cilia function, governed in part by the activity
      of intraflagellar transport (IFT). In articular cartilage, primary cilia length
      is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we
      examine primary cilia length with exposure to the quintessential inflammatory
      cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the
      hypothesis that the cilium is involved in mediating the downstream inflammatory
      response. Primary chondrocytes treated with IL-1 exhibited a 50% increase in
      cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed
      in human fibroblasts. In chondrocytes, this elongation occurred via a protein
      kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also
      regulated the length of chondrocyte primary cilia but not downstream of IL-1.
      Chondrocytes treated with IL-1 exhibit a characteristic increase in the release
      of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in
      cells with a mutation in IFT88 whereby the cilia structure is lost, this response
      to IL-1 was significantly attenuated and, in the case of nitric oxide, completely
      abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also
      attenuated the chemokine response. These results suggest that cilia assembly
      regulates the response to inflammatory cytokines. Therefore, the cilia proteome
      may provide a novel therapeutic target for the treatment of inflammatory
      pathologies, including OA.

PMID- 22481445
TI  - Prevention of hepatocellular carcinoma: a concise review of contemporary issues.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second
      leading cause of cancer deaths in men. Due to differences in the prevalence of
      viral hepatitis, the incidence of HCC in low and middle income countries is much
      higher than that of high income countries. Strategies to limit the impact of HCC
      include primary prevention against new cases of viral hepatitis, secondary
      prevention of HCC in susceptible individuals, and early HCC detection. Universal
      hepatitis B vaccination has resulted in dramatic reduction in incident cases of
      chronic hepatitis B and HCC in children and adolescents, and the full effect is
      expected in the next 20 years. The key hurdle for universal vaccination is the
      cost and the accessibility in low and middle income countries. Randomized
      controlled trials and meta-analyses showed that successful treatment of chronic
      hepatitis B and C can reduce the risk of HCC and cirrhotic complications. HCC
      surveillance by regular ultrasound examination and alpha fetoprotein testing
      leads to early cancer detection and offers the opportunity for curative
      treatment. Since all these measures are costly and require manpower and
      infrastructure support, the implementation should rely on the liaison among
      healthcare providers and policymakers. The cost-effectiveness of various
      strategies should also be studied based on local situations.

PMID- 22481446
TI  - Treatment of hyperferritinemia.
AB  - Elevated serum ferritin, or hyperferritinemia, is a common finding on routine
      bloodwork and often prompts referral for further evaluation. In the following
      review, we outline the various causes of hyperferritinemia and point out that, in
      the majority of cases, this does not represent true iron overload. Despite much
      research interest in this area, the precise mechanism of hyperferritinemia and
      its impact on disease severity in various clinical conditions continues to be
      debated. While some research suggests that iron reduction  in  cases  of 
      hyperferritinemia  is  of  benefit,  the  decision  to  treat  such  patients 
      should  be individualized, and may be influenced by the presence of other
      features of iron overload.

PMID- 22481447
TI  - Acute kidney injury in critically ill cirrhotic patients: a review.
AB  - Acute kidney injury (AKI) is an important marker of morbidity and mortality in
      critically ill cirrhotic patients. The most common causes of AKI in cirrhotic
      patients include prerenal or hepatorenal syndrome (HRS). Diagnosis of AKI may be
      delayed by the lack of clinical, biochemical, and radiological markers with
      proven sensitivity and specificity in cirrhotic patients. In this review, we
      discuss the epidemiology, pathophysiology, diagnosis, and therapies for AKI in
      cirrhotic patients admitted to an intensive care unit (ICU).

PMID- 22481448
TI  - Different models in predicting the short-term prognosis of patients with
      hepatitis B virus-related acute-on-chronic liver failure.
AB  - BACKGROUND AND AIMS: Effective assessing the prognosis of patients with end-stage
      liver disease is always challenging. This study aimed to investigate the accuracy
      of different models in predicting short-term prognosis of patients with hepatitis
      B virus (HBV)-related acute-on-chronic liver failure (ACLF). MATERIAL AND
      METHODS: We retrospectively evaluated survival of a cohort of patients with at
      least 3-month follow up. The receiver-operating-characteristic curves (ROC) were
      drawn for Child-Turcotte-Pugh (CTP) classification, King's College Hospital (KCH)
      criteria, model for end-stage liver disease (MELD), MELD combined with serum
      sodium (Na) concentration (MELDNa), integrated MELD (iMELD) and logistic
      regression model (LRM). RESULTS: Of the 273 eligible patients, 152 patients
      (55.7%) died within 3-month follow up. In cirrhotic patients (n = 101), the AUCs
      of LRM (0.851), MELDNa (0.849), iMELD (0.845) and MELD (0.840) were all
      significantly higher than those of KCH criteria (0.642) and CTP (0.625) (all p <
      0.05), while the differences among LRM, MELD, MELDNa and iMELD were not
      significant, and the most predictive cutoff value was 0.5176 for LRM, 30 for
      MELDNa, 47.87 for iMELD and 29 for MELD, respectively. In non-cirrhotic patients
      (n = 172), the AUC of LRM (0.897) was significantly higher than that of MELDNa
      (0.776), iMELD (0.768), MELD (0.758), KCH criteria (0.647) and CTP (0.629),
      respectively (all p < 0.05), and the most predictive cutoff value for LRM was 
      0.3264. CONCLUSIONS: LRM, MELD, MELDNa and iMELD are with similar accuracy in
      predicting the shortterm prognosis of HBV-ACLF patients with liver cirrhosis,
      while LRM is superior to MELD, MELDNa and iMELD in predicting the short-term
      prognosis of HBV-ACLF patients without liver cirrhosis.

PMID- 22481449
TI  - Is there an association between the measurement of qualitative  HBsAg and
      virologic response in chronic HBV infection?
AB  - BACKGROUND: In the follow up of chronic hepatitis B infection (HBV), a
      significant correlation between quantitative HBsAg titer measurement and HBV DNA
      level, and moreover with intrahepatic covalently closed circular DNA was already
      shown. However, besides their impact on long-term follow up, they are really
      expensive methods, and not available widespread. We aimed to investigate the
      utility of qualitative measurement of HBsAg titer in prediction of virologic
      response at the end of the first year of anti-viral treatment in chronic HBV
      infection. MATERIAL AND METHODS: A total of 70 patients receiving anti-viral
      therapies for chronic HBV infection were included into the study. The patients
      were evaluated according to Hbe Ag status and response to treatment. The
      determinations used in the study (biochemical, virologic responses, primary non
      response) were accepted as it was described in AASLD. RESULTS: Qualitative HBsAg
      titer increased significantly in both HBeAg positive and negative patients (p
      values 0.002 and < 0.000). Increasing of HBsAg titer in first three months is
      more dramatic in responder group, however the difference was disappeared at the
      sixth and twelve moths on follow up. Similarly, a fast increasing in anti-HBe
      titer in HBeAg negative chronic HBV patients was related with higher response at
      the end of first year therapy. However, the changings at the 12th month of anti
      viral treatment were similar in both responder and non-responder groups.
      CONCLUSION: In conclusion, the fast increase in qualitative measurement of HBsAg
      titer seemed to be a predictor of higher anti-viral medication success in chronic
      HBV patients. However, this meaningful increasing was disappeared on the follow
      up, particularly after the six months examination.

PMID- 22481450
TI  - Hepatitis A vaccination in healthcare personnel.
AB  - BACKGROUND AND AIMS: Despite effective vaccine available, hepatitis A remains a
      significant cause of morbidity and mortality worldwide including acute liver
      failure, transplantation and death. Vaccination rates for hepatitis A in the
      general population are low. Rates of hepatitis A vaccination in healthcare
      personnel (HCP) are unknown. We studied vaccination rate to hepatitis A in a
      cohort of HCP at a large US academic center. MATERIAL AND METHODS: An anonymous
      survey was circulated between 499 HCP at-risk of hepatitis A exposure at our
      Institution. Results were corrected for non-response rate and compared with the
      general US population using the 2007 CDC-National Immunization Survey. Rate of
      hepatitis A vaccination was compared with Institutional rate of vaccination for
      the Influenza 2009-2010 season. RESULTS: Rate of vaccination for hepatitis A in
      HCP was 28.8% (response rate 41.4%; 207/499), with 58.9% having completed the
      full series and 24.7% being tested for post-vaccination immunity. Acceptance rate
      among non-vaccinated subjects was 70.7%. HCP hepatitis A vaccination rate was
      statistically greater than the national general population (28.8 vs. 12.1%, p <=
      0.031). A statistically significant greater vaccination rate was found among US
      born responders vs. foreign-born HCP (34.3 vs. 19.3%, p = 0.0324). Vaccination
      for hepatitis A was statistically inferior to that of Influenza (28.8 vs. 90%; P
      = 0.01). CONCLUSIONS: HCP have statistically higher vaccination rate for
      hepatitis A than the general population, but overall protection remains
      suboptimal with vaccination rate below those for mandatory vaccines. Further
      studies to determine whether hepatitis A vaccine is cost-effective in HCP are
      recommended.

PMID- 22481451
TI  - Hepatitis B virus prevalence and vaccination response in health care workers and
      students at the Federal University of Bahia, Brazil.
AB  - BACKGROUND AND RATIONALE FOR THE STUDY: Hepatitis B (HB) is one of the most
      prevalent occupational infections in health attendance environments. According to
      the Brazil Ministry of Health, health professionals must be vaccinated against
      the hepatitis B virus (HBV) and provide laboratory proof of immunization. AIMS:
      To evaluate the seroprevalence of HBV infection and to analyze the response to
      vaccine by measuring serum antibodies against HBV surface antigen (anti-HBs)
      levels in a sample of students and health professionals at the Federal University
      of Bahia. RESULTS: As part of this cross-sectional study, a campaign against
      occupational HB was launched in 2007 and vaccination and blood samples were
      collected for analysis of the following serological markers: HBV surface antigen
      (HBsAg) and anti-HBs (measured by enzyme-linked immunoassay) and total antibodies
      against HBV core antigen (anti-HBc). The study sample comprised 766 people.
      Global seropositivity for HBV was 1.7%: 0.5% in the students and 8.8% in the
      professionals. In a group of volunteers, a serological profile compatible with
      postvaccine immunity was shown by 95% of volunteers with proof of vaccination and
      by 81.8% of volunteers without proof of vaccination. CONCLUSIONS: In conclusion,
      this study shows that it is important to promote vaccination campaigns and
      improve knowledge and awareness about HB among health care workers and higher
      education students.

PMID- 22481452
TI  - Treatment of recurrent genotype 4 hepatitis C after liver transplantation: early
      virological response is predictive of sustained virological response. An AISF
      RECOLT-C group study.
AB  - INTRODUCTION: Hepatitis C virus genotype 4 is predominant in the Middle East and
      Northern Africa, even if it has recently spread to Southern Europe. Data about
      the treatment of post-liver transplantation (LT) genotype 4 hepatitis C
      recurrence are scarce. We report a retrospective analysis of post-LT genotype 4
      hepatitis C treatment in 9 Italian transplant centres, focusing on the overall
      survival rates and treatment outcome. RESULTS: Among 452 recipients, we
      identified 17 HCV genotype 4 patients (16 males, 1 female) transplanted between
      1998 and 2007. All patients received combined antiviral treatment with
      conventional doses of interferon (recombinant or pegylated) and ribavirin after
      histological diagnosis of hepatitis C recurrence. The observed overall survival
      after LT was 100% at 1 year and 83.3% at 5 years. More than 1/3 (35.3%) of
      patients achieved a sustained virological response (SVR) and 40% (data available
      in 15 subjects) an early virological response (EVR), which was significantly
      associated with the achievement of SVR (overall accuracy: 85.7%; predictive
      values of EVR absence/presence 80/88.8%; chi-square p < 0.05). CONCLUSION: In
      conclusion, in post-LT genotype 4 hepatitis C treatment, SVR rates are similar to
      genotype 1. Patients who don't show an EVR are not likely to achieve a SVR.

PMID- 22481453
TI  - Serum adipocyte fatty acid binding protein in liver transplant recipients and the
      metabolic syndrome.
AB  - BACKGROUND: Liver transplantation is often associated with metabolic
      derangements. Adipocyte fatty-acid-binding protein 4 (AFABP4) integrates
      inflammatory and metabolic responses. It has also been associated with metabolic
      syndrome in animal models and clinical studies in the general population. AIM: To
      determine the role of AFABP4 in post-transplant metabolic syndrome. MATERIAL AND
      METHODS: Consecutive patients followed for at least 6 months after liver
      transplantation were tested for insulin resistance by homeostasis model
      assessment (HOMA). Serum levels of AFABP4 were tested by an enzyme-linked
      immunosorbent assay. RESULTS: The study group included 76 patients (64.5% male,
      mean age 56.3 +/- 12.4 years). Hypertension was present in 56.5%, hyperlipidemia
      in 69.7%, diabetes mellitus in 23.6%. Half of the patients met at least 3
      criteria for metabolic syndrome. Serum AFABP4 levels (p < 0.0001), HOMA index >=
      2.5 vs. < 2.5 (p < 0.0002) and BMI >= 30 vs. < 30 (p < 0.0006) were significantly
      higher in patients with metabolic syndrome. Within the metabolic syndrome
      subgroup, AFABP4 levels significantly correlated with age, aspartate
      aminotransaminase level, waist circumference, and HOMA index. High AFABP4
      significantly increased the odds of acquiring metabolic syndrome (OR 1.04, 95% CI
      1.007-1.074, p = 0.017). On multiple logistic regression analysis, independent
      predictors of high AFABP4 were cryptogenic liver disease, steroid administration,
      high HOMA index, and a high degree of fatty infiltration. CONCLUSION: Prevalence
      of metabolic syndrome is significantly higher in liver transplant recipients than
      in the general population. AFABP4 may serve as a circulating biomarker in the
      clinical prediction/diagnosis of metabolic syndrome in patients post-liver
      transplantation.

PMID- 22481454
TI  - High coffee intake is associated with lower grade nonalcoholic fatty liver
      disease: the role of peripheral antioxidant activity.
AB  - BACKGROUND & AIMS: Some phytochemicals present in coffee have a potential
      antioxidant role which seems to protect the human body against cardiovascular
      diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a
      common disease with limited therapeutic options. This study investigated the
      antioxidant effect of coffee by measuring antioxidant enzymes and lipid
      peroxidation markers in patients with nonalcoholic fatty liver disease. MATERIAL
      AND METHODS: We performed a case-control study at the University Hospital, Mexico
      City. Anthropometric, metabolic, dietary and biochemical variables of all
      patients were determined and compared. The presence of nonalcoholic fatty liver
      disease was established by ultrasonography. All patients completed a dietary
      questionnaire in order to determine their of coffee consumption. Catalase,
      superoxide dismutase and thiobarbituric acid reactive substances were measured in
      all of the patients. RESULTS: Seventy-three subjects with and 57 without
      nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty
      liver disease had significantly higher body mass index, blood glucose,
      homeostasis model of assessment-insulin resistance and insulin values in
      comparison to patients without nonalcoholic fatty liver disease. On the one hand,
      there was a significant difference in coffee intake between the groups (p < 0.05,
      for all comparisons). There was no significant difference between groups in
      catalase (0.39 +/- 0.74 vs. 0.28 +/- 0.69 nM/min/mL), superoxide dismutase (5.4
      +/- 3.45 vs. 4.7 +/- 2.1 U/mL) or thiobarbituric acid-reactive substances (4.05
      +/- 1.87 vs. 3.94 +/- 1.59 uM/mL). CONCLUSIONS: A high intake of coffee has a
      protective effect against nonalcoholic fatty liver disease however there was no
      significant difference in the antioxidant variables analyzed.

PMID- 22481455
TI  - Association between butyrylcholinesterase activity and low-grade systemic
      inflammation.
AB  - BACKGROUND: Pro-inflammatory cytokine production is directly inhibited by
      acetylcholine (ACh), and a relationship between total circulating ACh hydrolytic
      capacity and inflammatory reactions has been previously reported.
      Butyrylcholinesterase (BChE) is the major ACh hydrolyzing enzyme in plasma, and
      the aim of our study was to evaluate its association with low-grade systemic
      inflammation. MATERIAL AND METHODS: A total of 4,077 patients clinically managed
      in the Cardiology, Hypertension, and Digestive Medicine Units were included in
      our study. Three subclinical chronic inflammatory degrees were established in
      accordance with the high-sensitivity C-reactive protein (hsCRP) concentrations
      proposed, for low (< 1 mg/L), average (1-3 mg/L), and high (> 3-10 mg/L)
      cardiovascular disease risk estimation. RESULTS: In male patients with
      subclinical chronic inflammation and hsCRP concentrations < 1 mg/L, a significant
      positive correlation was observed between BChE and hsCRP (p < 0.02); however, for
      hsCRP concentrations > 3 mg/L, the correlation between these variables in both
      sexes becomes significantly negative (p < 0.001), as in patients with acute
      inflammation (hsCRP > 10 mg/L). In all cases significant positive correlations
      were obtained between the BChE activities and albumin concentrations (p < 0.001).
      CONCLUSIONS: The liver production of BChE and albumin occurs in a coupled
      fashion, and these biochemical variables may be considered as negative
      inflammatory reactants, whose serum levels are inversely associated with the
      increasing degree of subclinical inflammation.

PMID- 22481456
TI  - Non-invasive markers of liver fibrosis in chronic liver disease in a group of
      Mexican children. A multicenter study.
AB  - INTRODUCTION: Identifying liver fibrosis is important to evaluate the severity of
      liver damage and to establish a prognosis. Utility of non-invasive markers of
      liver fibrosis has been proved in adults but there are few reports in children.
      The aim of this study was to evaluate Fibrotest(r) score and APRI suitability to
      identify children with liver fibrosis. MATERIAL AND METHODS: 68 children with
      chronic liver disease requiring liver biopsy were prospectively included from
      three 3rd-level pediatric hospitals. The same pathologist evaluated all liver
      biopsies; fibrosis degree was determined by METAVIR score. Serum samples were
      obtained to determine Fibrotest(r) and APRI. AUROC were used to determine cut-off
      and differentiate between advanced fibrosis (METAVIR F3, F4) and no fibrosis
      (F0). RESULTS: 68 biopsies were evaluated; METAVIR > F3 was identified in 26
      (38%). Non invasive liver fibrosis markers to differentiate between advanced and
      no fibrosis were: Fibrotest(r) AUROC = 0.90 (95% CI 0.77-1.00) (cut-off value
      0.35) sensitivity 88.00% (95% CI 68-96) and specificity 80% (95% CI 29-98); and
      for APRI AUROC = 0.97 (95% CI 0.92-1.00) (cut-off value 0.82), sensitivity 88%
      (95% CI 68-96) and specificity = 100% (95% CI 46-100). CONCLUSION: These results
      suggest the utility of Fibrotest(r) and APRI to identify advanced fibrosis; they
      can be recommended to select patients for liver biopsy and during patient follow
      up.

PMID- 22481457
TI  - Meta-analysis: beta-blockers versus banding ligation for primary prophylaxis of
      esophageal variceal bleeding.
AB  - AIM: To perform an updated meta-analysis comparing beta-blockers (BB) with
      endoscopic variceal banding ligation (EVBL) in the primary prophylaxis of
      esophageal variceal bleeding. MATERIAL AND METHODS: Randomized controlled trials
      were identified through electronic databases, article reference lists and
      conference proceedings. Analysis was performed using both fixed-effect and random
      effect models. Heterogeneity and publication bias were systematically taken into
      account. Main outcomes were variceal bleeding rates and all-cause mortality,
      calculated overall and at 6, 12, 18 and 24 months. RESULTS: 19 randomized
      controlled trials were analyzed including a total of 1,483 patients. Overall
      bleeding rates were significantly lower for the EVBL group: odds ratio (OR) 2.06,
      95% confidence interval (CI) [1.55-2.73], p < 0.0001, without evidence of
      publication bias. Bleeding rates were also significantly lower at 18 months (OR
      2.20, 95% CI [1.04-4.60], P = 0.04), but publication bias was detected. When only
      high quality trials were taken into account, results for bleeding rates were no
      longer significant. No significant difference was found for either bleeding
      related mortality or for all-cause mortality overall or at 6, 12, 18 or 24
      months. BB were associated with more frequent severe adverse events (OR 2.61, 95%
      CI 1.60-4.40, P < 0.0001) whereas fatal adverse events were more frequent with
      EVBL (OR 0.14, 95% CI 0.02-0.99, P = 0.05). CONCLUSION: EVBL appears to be
      superior to BB in preventing the first variceal bleed, although this finding may
      be biased as it was not confirmed by high quality trials. No difference was found
      for mortality. Current evidence is insufficient to recommend EVBL over BB as
      first-line therapy.

PMID- 22481458
TI  - Hepatoprotective effect of the selective mineralocorticoid receptor antagonist,
      eplerenone against carbon tetrachloride-induced liver injury in rats.
AB  - BACKGROUND: Eplerenone is a selective mineralocorticoid receptor (MR) antagonist,
      and its potential protective role in cardiovascular injury has been reported by
      several studies. However, whether and how this drug can ameliorate hepatic injury
      in rats is unknown. MATERIAL AND METHODS: The present study was conducted to
      investigate effect of eplerenone against liver injury induced by carbon
      tetrachloride (CCl(4)) in rats. The biochemical liver function tests and
      oxidative stress parameters including malondialdehyde (MDA), reactive oxygen
      species (ROS), in addition to the reduced glutathione (GSH) levels were
      evaluated. Moreover, serum tumor necrotic factors (TNF-alpha) level and
      histopathological changes were examined. RESULTS: Our results show that pre
      treatment with eplerenone (4 mg/kg per day for 4 weeks) revealed attenuation in
      serum activities of alanine aminotransferase (ALT), aspartate aminotransferase,
      (AST), alkaline phosphatase (ALP) and bilirubin levels that were enhanced by
      CCl(4). Further, pre-treatment with eplerenone inhibited the elevated hepatic MDA
      content and restored hepatic GSH to its normal level. The enhanced hepatic ROS
      production in CCl(4)-treated group was markedly decreased by eplerenone
      administration. Eplerenone pre-treatment significantly attenuated the
      inflammatory responses caused by CCl(4) as evident by the decreased serum TNF
      alpha level. Histopathological studies showed that eplerenone alleviated the
      liver damage and reduced the lesions caused by CCl(4). CONCLUSION: Collectively,
      the present study provides a proof to hepatoprotective actions of eplerenone via
      reducing oxidative stress and inflammatory responses in CCl(4)-induced liver
      damage in rat model.

PMID- 22481459
TI  - Cardiac metastasis of hepatocellular carcinoma in a young non-cirrhotic patient,
      to the left ventricle.
AB  - Hepatocellular carcinoma (HCC) is the most common primary tumor of the
      liver.(1,2) The most common extrahepatic metastatic sites are lung, abdominal
      lymph nodes and bone, while its cardiac metastasis is rare.(2,3) Metastasis of
      HCC into the cardiac cavity is mostly caused by direct tumor invasion of vena
      cava inferior with continuous extension into the right cardiac cavity.(4,5) Right
      heart metastasis without invasion of inferior vena cava, which may be caused by
      hematogenous spread of cancer cells, is rarely reported.(6,7) This paper
      announces an unusual case of isolated involvement of left ventricle (LV) together
      with myocardial invasion of HCC. Our patient is known to be the first case with
      isolated HCC metastasis to the left ventricle. Strikingly, the patient was young
      and non-cirrhotic with negative serum HBsAg, and anti-HCV results.

PMID- 22481460
TI  - Living Fasciola hepatica in biliary tree: a case report.
AB  - Here we report a rare case of living Fasciola hepatica in biliary tract. The
      patient was in acute phase of infection and treated successfully with 10 mg/kg
      oral triclabendazole after the fluke was extracted using endoscopic retrograde
      cholangiopancreatography (ERCP).

PMID- 22481461
TI  - Hepatic hemodynamics and transient elastography in alcoholic foamy degeneration:
      report of 2 cases.
AB  - Alcoholic liver disease (ALD) covers a wide spectrum of pathology ranging from
      fatty liver disease to acute steatohepatitis to cirrhosis and/or hepatocellular
      carcinoma. Alcoholic foamy degeneration (AFD) is an uncommon, potentially life
      threatening condition that is part of the spectrum of ALD. It is characterized by
      extensive microvesicular steatosis in the perivenular areas. Since the first
      description in 1983, few case reports have been described. Here, we report 2
      cases of AFD in patients with a previous history of chronic alcohol abuse and
      histological diagnosis of AFD with typical clinical, biochemical and histological
      features. In both cases we provide data on the hepatic hemodynamic status, and in
      one of them we report liver elastography results, which are features that have
      not been described previously. In both cases there was rapid resolution of
      biochemical and clinical abnormalities after complete abstinence, which is the
      mainstay of treatment for AFD.

PMID- 22481462
TI  - Successful antiviral treatment of chronic hepatitis C in patients with rare
      comorbidities. Two case-reports.
AB  - Antiviral therapy in patients suffering from chronic hepatitis C virus (HCV)
      infection and rare comorbidities cannot be easily started, as it can reduce the
      likelihood of a good therapeutic response with an increased frequency of side
      effects. We report two patients presenting unusual comorbidities associated with
      chronic C hepatitis: one with the Ehlers-Danlos Syndrome (EDS), a rare genetic
      disease caused by a defect in collagen synthesis, the other one with the Charcot
      Marie Tooth (CMT) disease, an uncommon but severe form of demyelinating
      peripheral neuropathy. Both patients were successfully treated with pegylated
      Interferon (Peg-IFN) and ribavirin (RBV) combined therapy, with the achievement
      of a sustained viral response (SVR) and a low occurrence of adverse effects. Up
      to now there are no reports of patients suffering from chronic C hepatitis
      associated with these uncommon but severe comorbidities treated with antiviral
      therapy. In conclusion, in such clinical situations, anti-HCV therapy may be
      started and tailored, especially if the patient is highly motivated and if
      optimal predictors of response (i.e. young age, favourable genotype and low
      baseline viraemia) do exist.

PMID- 22481463
TI  - Acetylcholinesterase and butyrylcholinesterase as markers of low-grade systemic
      inflammation.

PMID- 22481464
TI  - Does the persistently normal aminotransferase levels in hepatitis C still have
      relevance?

PMID- 22481466
TI  - Hepatotoxicity associated with statins.

PMID- 22481465
TI  - Causes of death after liver transplantation.

PMID- 22481467
TI  - (1)H, (15)N and (13)C resonance assignments for the three LOTUS RNA binding
      domains of Tudor domain-containing protein TDRD7.
AB  - The LOTUS or OST-HTH domain is a recently discovered motif of about 80 amino
      acids and is found in several germline-specific proteins including the Tudor
      domain-containing proteins TDRD5 and TDRD7, which are important for germ cell
      development. The LOTUS domain is an RNA binding domain but its exact function is
      unknown. Here, we report the (1)H, (13)C and (15)N resonance assignments for the
      three LOTUS domains present in mouse TDRD7. These assignments will allow three
      dimensional structure determination of the LOTUS domains and mapping of their
      interaction with RNA, steps toward deciphering the function of TDRD7.

PMID- 22481468
TI  - (1)H, (13)C and (15)N resonance assignments of the C-terminal DNA-binding domain
      of RstA protein from Klebsiella pneumoniae.
AB  - Bacterial cells often use two-component signal transduction systems to regulate
      genes in response to environmental stimuli. The RstA/RstB system is a two
      component regulatory system consisting of the membrane sensor, RstB, and its
      cognate response regulator RstA. The RstA of Klebsiella pneumoniae consists of a
      N-terminal receiver domain (NRD, residues 1-119) and a C-terminal DNA-binding
      domain (DBD, residues 130-236). Phosphorylation of the response regulator induces
      a conformational change in the regulatory domain of RstA, which results in
      activation of the effector domain to regulate the downstream genes, including the
      ferrous iron transport system (Feo), at low-pH condition. Here we report the
      (1)H, (13)C and (15)N resonance assignments and secondary structure
      identification of the DBD of RstA from K. pneumoniae as a first step for
      unraveling the structural and functional relationship of the RstA/RstB two
      component system.

PMID- 22481469
TI  - One-step synthesis of a sulfur-impregnated graphene cathode for lithium-sulfur
      batteries.
AB  - A practical route is introduced for synthesizing a sulfur-impregnated graphene
      composite as a promising cathode material for lithium-sulfur batteries. Sulfur
      particles with a size of a few microns are successfully grown in the interior
      spaces between randomly dispersed graphene sheets through a heterogeneous crystal
      growth mechanism. The proposed route not only enables the control of the particle
      size of active sulfur but also affords quantitative yields of composite powder in
      large quantities. We investigate the potential use of the sulfur-impregnated
      graphene composite as a cathode material owing to its advantages of confining
      active sulfur, preventing the dissolution of soluble polysulfides, and providing
      sufficient electrical conduction. A high discharge capacity of 1237 mA h g(-1)
      during the first cycle and a good cyclic retention of 67% after 50 cycles are
      attained in a voltage range of 1.8-2.6 V vs. Li/Li(+). These results emphasize
      the importance of tailoring cathode materials for improving the electrochemical
      properties of lithium-sulfur batteries. Our results provide a basis for further
      investigations on advanced lithium batteries. 

PMID- 22481470
TI  - Extension of RPI-adult male and female computational phantoms to obese patients
      and a Monte Carlo study of the effect on CT imaging dose.
AB  - Although it is known that obesity has a profound effect on x-ray computed
      tomography (CT) image quality and patient organ dose, quantitative data
      describing this relationship are not currently available. This study examines the
      effect of obesity on the calculated radiation dose to organs and tissues from CT
      using newly developed phantoms representing overweight and obese patients. These
      phantoms were derived from the previously developed RPI-adult male and female
      computational phantoms. The result was a set of ten phantoms (five males, five
      females) with body mass indexes ranging from 23.5 (normal body weight) to 46.4 kg
      m(-2) (morbidly obese). The phantoms were modeled using triangular mesh geometry
      and include specified amounts of the subcutaneous adipose tissue and visceral
      adipose tissue. The mesh-based phantoms were then voxelized and defined in the
      Monte Carlo N-Particle Extended code to calculate organ doses from CT imaging.
      Chest-abdomen-pelvis scanning protocols for a GE LightSpeed 16 scanner operating
      at 120 and 140 kVp were considered. It was found that for the same scanner
      operating parameters, radiation doses to organs deep in the abdomen (e.g., colon)
      can be up to 59% smaller for obese individuals compared to those of normal body
      weight. This effect was found to be less significant for shallow organs. On the
      other hand, increasing the tube potential from 120 to 140 kVp for the same obese
      individual resulted in increased organ doses by as much as 56% for organs within
      the scan field (e.g., stomach) and 62% for those out of the scan field (e.g.,
      thyroid), respectively. As higher tube currents are often used for larger
      patients to maintain image quality, it was of interest to quantify the associated
      effective dose. It was found from this study that when the mAs was doubled for
      the obese level-I, obese level-II and morbidly-obese phantoms, the effective dose
      relative to that of the normal weight phantom increased by 57%, 42% and 23%,
      respectively. This set of new obese phantoms can be used in the future to study
      the optimization of image quality and radiation dose for patients of different
      weight classifications. Our ultimate goal is to compile all the data derived from
      these phantoms into a comprehensive dosimetry database defined in the VirtualDose
      software.

PMID- 22481471
TI  - Evidence for inhibition of HIF-1alpha prolyl hydroxylase 3 activity by four
      biologically active tetraazamacrocycles.
AB  - Hypoxia inducible factor 1 (HIF-1) is central to the hypoxic response in mammals.
      HIF-1alpha prolyl hydroxylase 3 (PHD3) degrades HIF through the hydroxylation of
      HIF-1alpha. Inhibition of PHD3 activity is crucial for up-regulating HIF-1alpha
      levels, thereby acting as HIF-dependent diseases therapy. Macrocyclic polyamines
      which display high stability on iron-chelating may well inhibit the enzyme
      activity. Thus inhibition and interaction on catalytic PHD3 by four biologically
      active tetraazamacrocycles (1-4), which have two types of parent rings to chelate
      iron(ii) dissimilarly, were studied. The apparent IC(50) values of 2.56, 1.91,
      5.29 and 2.44 MUM, respectively, showed good inhibition potency of the four
      compounds. K(I) values were 7.86, 3.69, 1.59 and 2.92 MUM for 1-4, respectively.
      Different inhibition actions of the two groups of compounds were identified.
      Circular dichroism (CD) and fluorescence spectrometries proved that one type of
      compound has significant effects on protein conformation while another type does
      not. Computational methodology was constructed to employ the equilibrium geometry
      of enzyme active site with the presence of substrate competitive inhibitor.
      Iron(ii) coordination in the active site by inhibitors of this kind induces
      conformational change of the enzyme and blocks substrate binding.

PMID- 22481472
TI  - Sediment organic tin contamination promotes impoverishment of non-biting midge
      species communities in the Archipelago Sea, S-W Finland.
AB  - Chironomid species are a vital component in many benthic and terrestrial food
      webs; they have an important role in the detritus cycle, and are an important
      source of food for many species. We studied how tributyltin (TBT) in brackish
      water sediments affect the composition of chironomid species communities.
      Emergence traps were used at selected sites on a TBT gradient in the Archipelago
      Sea, S-W Finland. Increased sediment TBT concentration was associated with
      significant chironomid species turnover, which in turn was related to decreased
      species diversity (number of species and genera). However, the overall number of
      individuals did not decrease markedly with increasing TBT contamination. This
      suggests that the ecological role of chironomids in the food web may be preserved
      even under severe impoverishment of the chironomid community due to organic tin
      contamination. The increased prevalence of more TBT tolerant species can
      potentially lead to a transport of organic tin compounds between aquatic and
      terrestrial food webs. Furthermore, the reduced diversity of an ecologically
      influential group might lower the resistance of the entire food web to other
      environmental hazards and perturbations.

PMID- 22481473
TI  - New insights into the pathoanatomy of diabetic macular edema: angiographic
      patterns and optical coherence tomography.
AB  - PURPOSE: To describe the pathoanatomy of diabetic macular edema in optical
      coherence tomography and its correlation with fluorescein angiography patterns.
      METHODS: Sixty eyes of 56 patients were analyzed. Diabetic macular edema was
      classified into typical focal leakage (from microaneurysm), typical diffuse
      leakage (the capillary plexus), or combined/questionable leakage using
      fluorescein angiography and retinal thickness profiles. The leakage and pooling
      patterns in fluorescein angiography were matched to the corresponding optical
      coherence tomography images and analyzed. RESULTS: Focal leakage shows swelling
      predominantly in the outer plexiform layer (OPL). Deeply located microaneurysms
      directly leak into the loose fiber portion of OPL (Henle layer) through the
      "fluid conductivity barrier" (synaptic portion of OPL). Diffuse leakage caused
      swelling predominantly in the inner nuclear layer and secondarily in the OPL. The
      deep capillary plexus is located between the two "fluid barriers" (inner
      plexiform layer and OPL); thus, diffuse leakage is primarily related with
      swelling in the inner nuclear layer. In the combined/questionable leakage,
      partial sections consisting of inner nuclear layer swelling and much larger areas
      of OPL/outer nuclear layer swelling are noticed. CONCLUSION: Based on the concept
      of the fluid conductivity barrier, we revealed a correlation between the
      intraretinal location of the leakage source and where the fluid accumulated
      within the retinal layers.

PMID- 22481474
TI  - Vitrectomy for optic disk pit with macular schisis and outer retinal dehiscence.
AB  - PURPOSE: To describe the outcomes of vitrectomy for optic disc pit-related
      maculopathy with central outer retinal dehiscence. METHODS: This prospective
      interventional case series included seven patients with optic disc pit with
      macular schisis and central outer retinal dehiscence who underwent vitrectomy
      with internal limiting membrane peeling, barrage laser photocoagulation, and gas
      tamponade and were followed for at least 6 months. The surgical outcomes in terms
      of restoration of macular anatomy and visual improvement were recorded at each
      visit by fundus photography and optical coherence tomography. RESULTS: The mean
      age of the patients was 21.3 +/- 8.6 years (range, 10-35 years), and the mean
      duration of defective vision was 6.7 +/- 8.5 months (range, 1-24 months).
      Preoperatively, the median best-corrected visual acuity (BCVA) was 20/60 (range,
      20/40 to 20/120). Full-thickness macular holes were noticed in 4 patients 1 month
      postoperatively. Gas tamponade was repeated in two patients with large macular
      holes. By the final follow-up, macular holes had closed and BCVA improved in all
      patients except one. Final mean central macular thickness was 176.83 +/- 55.74
      MU, the range being 109 MU to 256 MU. The median postoperative BCVA was 20/30
      (range, 20/20 to 20/80). Six of 7 patients (85.7%) had improvement in BCVA
      postoperatively (mean, +2 lines; range, 1-4 lines). Five patients (71%) achieved
      a postoperative BCVA of >=20/30. Best-corrected visual acuity dropped by one line
      in the patient with persistent macular hole. CONCLUSION: Vitrectomy with internal
      limiting membrane peeling can achieve excellent final surgical outcomes in optic
      pit maculopathy with outer retinal dehiscence despite the potential for macular
      hole formation.

PMID- 22481475
TI  - The ARMS2 A69S variant and bilateral advanced age-related macular degeneration.
AB  - PURPOSE: To identify genetic associations between specific risk genes and
      bilateral advanced age-related macular degeneration (AMD) in a retrospective,
      observational case series of 1,003 patients: 173 patients with geographic atrophy
      in at least 1 eye and 830 patients with choroidal neovascularization in at least
      1 eye. METHODS: Patients underwent clinical examination and fundus photography.
      The images were subsequently graded using a modified grading system adapted from
      the Age-Related Eye Disease Study. Genetic analysis was performed to identify
      genotypes at 4 AMD-associated variants (ARMS2 A69S, CFH Y402H, C3 R102G, and CFB
      R32Q) in these patients. RESULTS: There were no statistically significant
      relationships between clinical findings and genotypes at CFH, C3, and CFB. The
      genotype at ARMS2 correlated with bilateral advanced AMD using a variety of
      comparisons: unilateral geographic atrophy versus bilateral geographic atrophy (P
      = 0.08), unilateral choroidal neovascularization versus bilateral choroidal
      neovascularization (P = 9.0 * 10(-8)), and unilateral late AMD versus bilateral
      late AMD (P = 5.9 * 10(-8)). CONCLUSION: In this series, in patients with
      geographic atrophy or choroidal neovascularization in at least 1 eye, the ARMS2
      A69S substitution strongly associated with geographic atrophy or choroidal
      neovascularization in the fellow eye. The ARMS2 A69S substitution may serve as a
      marker for bilateral advanced AMD.

PMID- 22481476
TI  - Long-term results of photodynamic therapy for subfoveal choroidal
      neovascularization with pathologic myopia.
AB  - PURPOSE: The purpose of our study was to determine the long-term visual and
      anatomic outcomes of photodynamic therapy in patients affected with choroidal
      neovascularization secondary to pathologic myopia. METHODS: We retrospectively
      evaluated 43 eyes of 43 patients. Patients with pathologic myopia were included
      if they had received photodynamic therapy for choroidal neovascularization
      involving the center of the avascular foveal zone and if they had a follow-up of
      at least 5 years. We included only the cases for which both of the examiners of
      the FAs were in agreement concerning the subfoveal localization of choroidal
      neovascularization. Patients treated with other therapies such as anti-vascular
      endothelial growth factor or steroids in the study eye were excluded. Visual
      acuity was measured using Early Treatment Diabetic Retinopathy Study charts.
      Anatomic outcome measures were the lesion size expressed as the greatest linear
      diameter and the chorioretinal atrophy that developed around the regressed
      choroidal neovascularization. RESULTS: Average visual acuity was stable during
      the first year, tended to be worse at 2 years, whereas it was significantly worse
      at 3 years and afterward, reaching a loss of nearly 3 lines at 7 years. We found
      that neither the number of photodynamic therapy treatments nor baseline
      photodynamic therapy spot size influenced change of visual acuity during follow
      up. Chorioretinal atrophy around choroidal neovascularization was detected in 83%
      of patients at the 5-year follow-up visit. CONCLUSION: The results showed that
      visual acuity decreased significantly after a long follow-up period mainly
      because of the development of chorioretinal atrophy.

PMID- 22481477
TI  - Use of spectral-domain optical coherence tomography to differentiate acquired
      retinoschisis from retinal detachment in difficult cases.
AB  - PURPOSE: This study presents a series of 10 patients who posed a diagnostic
      challenge regarding the diagnosis of acquired retinoschisis (RS) or retinal
      detachment (RD), where spectral-domain optical coherence tomography (OCT) with
      the Spectralis HRA and OCT device (Heidelberg Engineering, Heidelberg, Germany)
      was able to help make a correct diagnosis. METHODS: Ten patients (five with
      acquired RS and five with RD) were referred to a vitreoretinal clinic at
      Moorfields Eye Hospital for definitive diagnosis and further management. All
      patients underwent scans with the Spectralis HRA and OCT device. RESULTS: The
      Spectralis HRA and OCT was able to make a clear diagnosis of RS or RD in all
      patients. Of the five patients with RS confirmed on OCT, two were referred with
      RD, and of the five patients with RD, four were referred with RS. New OCT
      features of RS include the double schisis cavity phenomenon, intraretinal pillars
      through the schisis cavity, and irregularity of the inner surface of the attached
      outer leaf. CONCLUSION: Spectral-domain OCT is a useful tool in distinguishing RS
      from RD, eliminating previous diagnostic uncertainty. The Spectralis HRA and OCT
      device has the added advantages of being able to reliably image anterior retinal
      pathology and produce high-definition images.

PMID- 22481478
TI  - Effect of change in drusen evolution on photoreceptor inner segment/outer segment
      junction.
AB  - PURPOSE: To evaluate the integrity of photoreceptor inner segment/outer segment
      (IS/OS) junction after change of drusen size in age-related macular degeneration
      using spectral-domain optical coherence tomography. METHODS: Drusen volume raster
      scans were performed with the Spectralis spectral-domain optical coherence
      tomography (Heidelberg Engineering) through 2,624 drusen in 14 eyes with
      clinically dry age-related macular degeneration, which had been longitudinally
      followed-up between 23 and 28 months without intervention (mean, 26.3 months).
      All eyes had Early Treatment Diabetic Retinopathy Study visual acuity. A total of
      416 of 2,624 drusen were analyzed. RESULTS: Of 416 drusen, 83 (20%) were found to
      have regressed spontaneously (Group A), 212 (51%) showed no change in size (Group
      B), and 121 (29%) progressed (Group C). Mean drusen size of all drusen was 63.7
      +/- 25.7 MUm. Cross-sectional analysis of drusen morphology showed a correlation
      between drusen size and disrupted IS/OS junction/photoreceptor integrity (r = 
      0.48, P < 0.001). Of the drusen that regressed over time, there was intact IS/OS
      junction integrity. Even drusen that caused a major disruption showed IS/OS
      restoration in 74% of the drusen (P < 0.001). CONCLUSION: Progression of drusen
      shows structural disruption of the IS/OS junction. After drusen regression, the
      IS/OS junction is either able to restore as drusen regress or was
      artifactitiously compressed and not initially visible because of the initial
      drusen compression of the IS/OS junctional line. Therefore, drusen evolution may
      play an important role in affecting the photoreceptor IS/OS junction integrity.

PMID- 22481479
TI  - Intravitreal bevacizumab as primary treatment of choroidal neovascularization
      secondary to punctate inner choroidopathy: results of a 1-year prospective trial.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab as
      primary treatment of choroidal neovascularization secondary to punctate inner
      choroidopathy. METHODS: Twelve eyes of 12 patients with subfoveal or juxtafoveal
      choroidal neovascularization secondary to punctate inner choroidopathy received
      intravitreal bevacizumab injection (1.25 mg) in this prospective case series.
      Injection was repeated if persistent or recurrent activity of choroidal
      neovascularization was indicated by optical coherence tomography or fundus
      fluorescein angiography at 1-month intervals. Visual, clinical, angiographic, and
      anatomical changes were observed over a 12-month follow-up period. RESULTS: After
      12 months of follow-up, mean logarithm of the minimum angle of resolution best
      corrected visual acuity improved from 0.49 (20/62 in Snellen equivalent) at
      baseline to 0.23 (20/34 in Snellen equivalent; P < 0.001). Mean central retinal
      thickness determined by optical coherence tomography decreased from 333 MUm to
      241 MUm (P < 0.001). All eyes (100%) had stable or improved vision, and 9 eyes
      (75%) showed an improvement of >= 2 lines. All lesions converted to the
      cicatricial phase after 12 months of follow-up. No drug-related systemic or
      ocular side effects were observed. CONCLUSION: Intravitreal bevacizumab is well
      tolerated and improves best-corrected visual acuity in choroidal
      neovascularization secondary to punctate inner choroidopathy over a 12-month
      period.

PMID- 22481480
TI  - Early postoperative intraocular pressure stability after combined 23-gauge
      sutureless vitrectomy and cataract surgery in patients with proliferative
      diabetic retinopathy.
AB  - PURPOSE: To compare rates of early postoperative hypotony and intraocular
      pressure (IOP) elevation between 23-gauge sutureless vitrectomies with and
      without phacoemulsification and intraocular lens implantation in patients with
      proliferative diabetic retinopathy. METHODS: This study reviewed the medical
      records of 302 eyes of patients who underwent primary 23-gauge sutureless
      vitrectomy for the complications of proliferative diabetic retinopathy. A case
      series of 207 eyes that underwent combined vitrectomy and cataract surgery
      (combined group) was compared with that of 95 eyes that underwent vitrectomy only
      (vitrectomy group): The eyes that remained phakic after the vitrectomy were
      excluded from this study. The main outcome measures were postoperative hypotony
      (IOP < 6 mmHg or IOP < 10 mmHg with choroidal detachment) and IOP elevation (>30
      mmHg). RESULTS: Postoperative hypotony was identified in 4 (1.9%) of 207 eyes in
      combined group, but in 7 (7.4%) of 95 eyes in vitrectomy group (P = 0.048). Rate
      of IOP elevation was very low and not different between the two groups. The
      multivariate analysis showed that vitrectomy without cataract surgery was
      associated with the postoperative hypotony (odds ratio = 4.6, P = 0.045).
      CONCLUSION: The incidence of early postoperative hypotony was lower in combined
      sutureless vitrectomy and cataract surgery than in sutureless vitrectomy alone
      and that of IOP elevation was very low in both groups. The maintenance of a
      stable IOP with a low risk of IOP fluctuation may be an additional advantage of
      sutureless diabetic vitrectomy combined with cataract surgery.

PMID- 22481481
TI  - Long-term follow-up of inflammatory cystoid macular edema.
AB  - PURPOSE: To determine the long-term functional and anatomical outcome of
      idiopathic uveitic cystoid macular edema (UCME). METHODS: A longitudinal
      retrospective study was undertaken of the medical records of patients with UCME.
      All individuals were examined in the uveitis Service at the Moorfields Eye
      Hospital. The main outcome measures were change in visual acuity and anatomical
      outcome of UCME at diverse time points. RESULTS: A total of 109 eyes (92
      patients) with UCME were included in the analysis. Mean follow-up was 60 +/- 45
      months (median, 48 months). Mean logarithm of the minimum angle of resolution
      visual acuity 1 month after the intervention improved significantly (P < 0.001)
      by 0.21 +/- 0.27 and maintained at similar levels throughout the follow-up
      period. Visual acuity at the final follow-up improved in 75 eyes (69%), was
      deteriorated in 21 eyes (19%), and remained unchanged in 13 eyes (12%). Younger
      age and better visual acuity at baseline were associated with more favorable
      visual outcome (P < 0.001). Optical coherence tomography documentation of
      improvement or total resolution of UCME was observed in 84 eyes (77%) at the
      final follow-up. CONCLUSION: Cystoid macular edema is a major complication in
      uveitis. Current management provides satisfactory long-term results for the
      majority of those individuals. Visual acuity 1 month after the intervention is
      usually indicative of the final functional outcome.

PMID- 22481482
TI  - Disrupted foveal photoreceptors after combined cystoid spaces and retinal
      detachment in branch vein occlusion treated with bevacizumab.
AB  - PURPOSE: To investigate how combined cystoid spaces and serous retinal detachment
      affect photoreceptor status and visual acuity at final visit in macular edema
      associated with branch retinal vein occlusion. METHODS: Forty-seven consecutive
      eyes from 47 patients with macular edema associated with branch retinal vein
      occlusion treated with intravitreal bevacizumab injection were retrospectively
      reviewed. Foveal pathomorphology on optical coherence tomography images were
      divided into two groups: those in which combined foveal cystoid spaces and serous
      retinal detachment were observed at least once (C+S(+)) and those in which they
      were not observed (C+S(-)). The relationship between foveal pathomorphology and
      photoreceptor status and logarithm of the minimum angle of resolution at final
      visit was investigated. RESULTS: Sixteen eyes were categorized as C+S(+), and the
      final visual acuity of C+S(+) group was significantly worse than that of C+S(-)
      group compared with no difference at baseline. Intriguingly, combined foveal
      pathomorphologies during the course were significantly associated with the
      absence of external limiting membrane and the junction of inner and outer
      segments at last visit. Using multivariable analysis, final logarithm of the
      minimum angle of resolution was significantly related to baseline logarithm of
      the minimum angle of resolution, diabetes, and C+S(+). CONCLUSION: Combined
      foveal cystoid spaces and retinal detachment during follow-up predict the
      disrupted foveal photoreceptors and concomitant poor final visual acuity in
      branch retinal vein occlusion treated with intravitreal bevacizumab injection.

PMID- 22481483
TI  - Ion-induced surface relaxation: controlled bending and alignment of nanowire
      arrays.
AB  - It is a well-known fact that a sphere offers less surface area, and thus less
      surface  energy, than any other arrangement of the same volume. From this
      perspective, all other shapes are metastable objects. In this paper, we present
      and discuss a manifestation of this metastability: the spontaneous alignment of
      free-standing amorphous nanowires towards, and ultimately parallel to, a flux of
      directional ion irradiation. The behavior expected from surface energy reduction
      is the opposite of that predicted by both theory and experiment regarding defect
      generation in crystalline nanowires, but is consistent with other observations on
      non-crystalline materials. We verify our expectations by bending and aligning
      finely stranded amorphous silica nanowires, noting that such nanostructures are
      particularly susceptible to bending through ion-induced surface energy reduction.
      We offer support for this mechanism through bending rate studies, thermal
      annealing experiments and mathematical modeling. Experimentally, we also
      demonstrate selective reorientation of nanowires in patterned areas, as well as
      conformal coating of reoriented arrays with functional materials. These
      capabilities offer the prospect of exploiting engineered surface anisotropies in
      optical, fluidic and micromechanical applications.

PMID- 22481484
TI  - First principles study of the electric polarization and of its switching in the
      multiferroic GaFeO3 system.
AB  - The electric polarization in the multiferroic GaFeO(3) system is determined from
      its electronic structure using first principles methods and the modern theory of
      polarization. By carefully following the electric polarization on a path
      connecting the polar and centrosymmetric structures, it is found to be -25 MUC
      cm(-2), which is ten times larger than a previous estimation given in the
      literature a few years ago and two times smaller than the value obtained in a
      recent similar study. The switching of this electric polarization through a
      centrosymmetric structure is discussed in terms of the total energy barrier. It
      is exhibited that such a switching is particularly difficult to achieve in
      relation to the tetrahedral environment of half of the Ga atoms. The switching
      via domain wall motion is also discussed.

PMID- 22481486
TI  - Probing the history of nanotechnology.

PMID- 22481485
TI  - The dynamics of Abeta distribution after gamma-secretase inhibitor treatment, as
      determined by experimental and modelling approaches in a wild type rat.
AB  - Inhibition of the enzyme(s) that produce the Amyloid beta (Abeta) peptide, namely
      BACE and gamma-secretase, is considered an attractive target for Alzheimer's
      disease therapy. However, the optimal pharmacokinetic-pharmacodynamic modelling
      method to describe the changes in Abeta levels after drug treatment is unclear.
      In this study, turnover models were employed to describe Abeta levels following
      treatment with the gamma-secretase inhibitor RO5036450, in the wild type rat.
      Initially, Abeta level changes in the brain, cerebral spinal fluid (CSF) and
      plasma were modeled as separate biological compartments, which allowed the
      estimation of a compound IC50 and Abeta turnover. While the data were well
      described, the model did not take into consideration that the CSF pool of Abeta
      most likely originates from the brain via the CSF drainage pathway. Therefore, a
      separate model was carried out, with the assumption that CSF Abeta levels
      originated from the brain. The optimal model that described the data involved two
      brain Abeta 40 sub-compartments, one with a rapid turnover, from which CSF Abeta
      40 is derived, and a second quasi-static pool of ~20%. Importantly, the estimated
      in vivo brain IC50 was in a good range of the in vitro IC50 (ratio, 1.4). In
      conclusion, the PK/PD models presented here are well suited for describing the
      temporal changes in Abeta levels that occur after treatment with an Abeta
      lowering drug, and identifying physiological parameters.

PMID- 22481488
TI  - When less is more in a nanopore.

PMID- 22481489
TI  - Myosin shifts into reverse gear.

PMID- 22481491
TI  - A simple method for the preparation of hollow ZnO nanospheres for use as a high
      performance photocatalyst.
AB  - We have used classical electrospinning and subsequent thermal treatment to
      successfully fabricate hollow ZnO nanospheres. The hollow ZnO nanospheres were
      then used to study the degradation of Rhodamine B (RhB) dye and were proven to
      have excellent photocatalytic activity. The mechanism of formation of hollow ZnO
      nanospheres and the reason for the high photocatalytic activity were also
      investigated.

PMID- 22481492
TI  - Effect of platinum-containing chemotherapy on olfactory, gustatory, and hearing
      function in ovarian cancer patients.
AB  - PURPOSE: Most patients with epithelial ovarian cancer have a poor overall
      prognosis. Therefore, one of the main therapeutic aims after cytoreductive
      surgery for these patients is to identify, delay and relieve chemotherapy-induced
      side effects and optimise the quality of life, especially after first-line
      therapy. METHODS: Twelve ovarian cancer patients undergoing carboplatinum
      containing chemotherapy were assessed using validated tests for olfactory,
      gustatory, and hearing functions before, during, immediately after, and 3 months
      after chemotherapy. RESULTS: All chemosensory functions decreased during and
      after carboplatinum-containing chemotherapy, but recovered 3 months after
      treatment ended. For olfaction, this decrease was significant, affecting odour
      identification minimally, and odour threshold the most. For taste, the decrease
      was not significant, but could be observed in total scores and in each quality
      (sweet, sour, salty, and bitter). For hearing, the decrease was not significant,
      but a recovery of the deep and middle frequencies was clearly evident 3 months
      after chemotherapy. CONCLUSIONS: Patients must be informed about transient
      declines in chemosensory functions during chemotherapy. Symptomatic relief
      provided by the use of more spices, a small amount of glutamate, or additional
      flavouring might help to compensate for decreased functions during chemotherapy
      and increase patient quality of life.

PMID- 22481493
TI  - Massive hemothorax due to diaphragmatic endometriosis after a laparoscopic
      cystectomy of an ovarian endometrioma in a patient without a history of thoracic
      endometriosis.
AB  - BACKGROUND: Severe hemothorax is a rare complication after laparoscopic surgery
      for endometriosis, and the causes and proper management are not well understood.
      CASE: We report here the extremely rare case with massive hemothorax after
      laparoscopic surgery for ovarian endometrioma. A 40-year-old woman, gravida 1,
      para 1, underwent laparoscopic cystectomy of ovarian endometrioma. On
      postoperative day 2, she had progressive anemia (Hb 5.3) as well as dyspnea. A
      chest X-ray and computed tomography showed massive fluid collection in the right
      thoracic cavity, suggestive of intrapleural bleeding. TREATMENT: Thoracoscopic
      operation was performed and a total of 930 ml of blood retention in the right
      thoracic cavity was found. Scattered small endometriotic lesions were present on
      the pleural surface of the right diaphragm; pulsatile active bleeding was
      confirmed from one of these. Furthermore, two endometriotic lesions had
      perforated into the intraperitoneal cavity. The diaphragm containing bleeding
      spots was thoracoscopically resected and sutured. After thoracoscopic surgery,
      the dyspnea and anemia resolved. On postoperative day 5, the patient left the
      hospital. CONCLUSION: The present report reminds us of the importance of paying
      special attention to postoperative-thoracic complications caused by diaphragmatic
      endometriosis if the patient shows respiratory symptoms.

PMID- 22481494
TI  - Intrauterine death of a child with Goldenhar syndrome: a case presentation and
      review of the literature.

PMID- 22481495
TI  - Nodular lesions of self-healing juvenile cutaneous mucinosis: a pitfall!
AB  - Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder of unknown
      origin, which occurs in children in good health. It is characterized by the
      multiplication of transient cutaneous papules and nodules, mainly located on the
      head and periarticular areas that spontaneously resolve. Histological features of
      SHJCM have been well described; therefore, the diagnosis is usually made easily
      when papules are biopsied. We report a series of 3 new cases of SHJCM presenting
      mainly with nodular lesions. Histological examination of these nodules showed
      either lesions consistent with nodular or proliferative fasciitis or nonspecific
      panniculitis. Mucinous deposits were present but often inconspicuous, so could be
      disregarded. We wanted to emphasize this misleading presentation because a biopsy
      for histological examination is always mandatory in cases of proliferating
      nodules to rule out malignant tumors. Therefore, the diagnosis always requires
      discussion between pathologists and clinicians to rapidly reassure the parents
      and avoid inappropriate therapy.

PMID- 22481496
TI  - Cowden syndrome: report of two cases with immunohistochemical analysis for PTEN
      expression.
AB  - Cowden syndrome (CS) is a rare autosomal dominant disorder characterized by
      multisystem hamartomatous growths and carcinomas. CS is linked to germ line
      mutations in PTEN (phosphatase and tensin homolog) located on chromosome 10q23.3.
      PTEN acts as a tumor suppressor to negatively control cellular growth and
      survival via the PI3K/AKT signaling pathway. Presented here are 2 patients with
      multiple, persistent, and asymptomatic papules on the face and the upper body,
      histologically consistent with trichilemmomas. Diagnosis of CS was made in each
      case based on the established diagnostic criteria and confirmed using
      immunohistochemistry directed against PTEN. We propose that the assessment of
      PTEN expression levels can aid in the identification of patients with CS.

PMID- 22481497
TI  - Extensive eosinophilic infiltrates in the epidermal cyst wall:  related to
      scrotal calcinosis?

PMID- 22481498
TI  - The melanocytic epithelioid cell nevus of the thigh of woman:  a simulator of
      melanoma.

PMID- 22481499
TI  - Familial acral localized late-onset focal dermal elastosis.
AB  - Late-onset focal dermal elastosis is a rare disorder of elastic tissue,
      characterized by a local accumulation of elastic fibers in the mid and deep
      reticular dermis. This disorder occurs mainly in elderly people and consists of
      multiple yellow papules that are typically distributed on the sides of the neck
      and flexural areas, closely resembling pseudoxanthoma elasticum from the clinical
      point of view. We report 2 sisters who have presented with a 20-year history of
      multiple yellow papules, mainly located on the dorsum of their hands. They also
      had few lesions of similar morphology scattered on the anterior aspects of their
      wrists, thighs, and lower abdomen. Histopathologic study demonstrated a focal
      increase in thick, interlacing elastic fibers in the mid and deep reticular
      dermis. The most striking features of our cases were the early age of clinical
      presentation, the familial involvement, and the predominantly acral distribution
      of the lesions.

PMID- 22481500
TI  - Magnetic resonance imaging-guided perineural therapy as a treatment option in
      young adults with pudendal nerve entrapment syndrome.

PMID- 22481501
TI  - Time-resolved cardiac interventional cone-beam CT reconstruction from fully
      truncated projections using the prior image constrained compressed sensing
      (PICCS) algorithm.
AB  - C-arm cone-beam CT could replace preoperative multi-detector CT scans in the
      cardiac interventional setting. However, cardiac gating results in view angle
      undersampling and the small size of the detector results in projection data
      truncation. These problems are incompatible with conventional tomographic
      reconstruction algorithms. In this paper, the prior image constrained compressed
      sensing (PICCS) reconstruction method was adapted to solve these issues. The
      performance of the proposed method was compared to that of FDK, FDK with
      extrapolated projection data (E-FDK), and total variation-based compressed
      sensing. A canine projection dataset acquired using a clinical C-arm imaging
      system supplied realistic cardiac motion and anatomy for this evaluation. Three
      different levels of truncation were simulated. The relative root mean squared
      error and the universal image quality index were used to quantify the
      reconstruction accuracy. Three main conclusions were reached. (1) The adapted
      version of the PICCS algorithm offered the highest image quality and
      reconstruction accuracy. (2) No meaningful variation in performance was observed
      when the amount of truncation was changed. (3) This study showed evidence that
      accurate interior tomography with an undersampled acquisition is possible for
      realistic objects if a prior image with minimal artifacts is available.

PMID- 22481503
TI  - Spinal anesthesia under sedation using propofol and ketamine for laparoscopic
      cholecystectomy in a patient during 13th week of gestation.

PMID- 22481502
TI  - Successful treatment by donor lymphocyte infusion of adult T-cell
      leukemia/lymphoma relapse following allogeneic hematopoietic stem cell
      transplantation.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive hematologic neoplasm
      that has an extremely poor prognosis; however, this has improved following recent
      progress in allogeneic hematopoietic stem cell transplantation (allo-HSCT).
      Several clinical studies have shown that discontinuation of immunosuppressant
      therapy induces durable remission in a significant number of post-transplant
      relapsed patients, suggesting that ATLL may be susceptible to a graft-versus
      leukemia effect. Here, we report two cases with ATLL who received donor
      lymphocyte infusions (DLIs) for relapse after allo-HSCT; one patient achieved
      complete remission (CR) after a single DLI, and the other suffered repeated
      relapses and was treated with chemotherapy and radiotherapy combined with a total
      of five rounds of DLIs. Both patients presented with exacerbation of the graft
      versus-host disease after the DLIs, and remained in CR for 9 and 8 years,
      respectively. These data support the use of DLIs as an effective therapy to
      induce durable CR in the treatment of relapsed ATLL. In this study, we review
      previous reports and discuss the role of DLIs in the treatment of post-transplant
      relapsed ATLL.

PMID- 22481504
TI  - [New aspects of Parkinson disease: introduction].

PMID- 22481505
TI  - [Cognitive impairment in patients with Parkinson disease].
AB  - Parkinson disease is a progressive neurodegenerative disorder resulting in motor
      symptoms and cognitive deficits. Neuropsychological studies have suggested that
      patients with Parkinson disease exhibit a broad range of cognitive deficits even
      in the early stages of the disease. In this review, we discuss the
      neuropsychological evidence for cognitive impairment in patients with Parkinson
      disease, outlining the different domains of cognitive disturbance. First, we
      review previous findings on executive dysfunction, which is associated with a
      disruption in frontostriatal circuitry mainly driven by dopaminergic
      dysmodulation. Executive dysfunction is the core symptom in the cognitive
      deficits in Parkinson disease. Second, we focus on impairment in different
      domains of memory function, such as short-term and long-term memory. Third, we
      discuss the pattern of cognitive deficits in visuospatial ability, ranging from
      basic perceptual processes to rather complex motor skills. Next, we summarize the
      profile of cognitive deficits in language, although previous findings are mixed
      and hence this topic is relatively controversial. Finally, we introduce several
      recent findings on social cognitive deficits, which is a new area of research
      that has emerged in the past decade. We also discuss the possible neural
      mechanisms underlying each domain of cognitive deficits in patients with
      Parkinson disease.

PMID- 22481506
TI  - [Depression and anxiety in Parkinson's disease].
AB  - Parkinson's disease (PD) is accompanied by nonmotor symptoms (NMS) such as mood
      disorders. Among them, depression and anxiety complicate PD and are present at
      high rates in PD patients. Organic depression is generally known to affect a
      patient's recovery from the sequelae of the primary disease; thus early detection
      and appropriate treatment are essential. Depression in PD is thought to result
      from different factors such as disappearance of neurons in the dopamine,
      noradrenaline, and serotonin as well as from psychogenic reactions associated
      with the onset of the disease. Moreover, anxiety may also be a side effect of PD
      treatment. As morbid states of depression and anxiety are complicated, these
      symptoms are often difficult to diagnose. Moreover, the validity of these
      diagnostic methods has not been established. Therefore, accurate diagnoses of
      morbid states in the early stage of the disease and corresponding appropriate
      treatments are vital.

PMID- 22481507
TI  - [Sleep disturbances in patients with Parkinson disease].
AB  - Sleep disturbances are among the most common disabling nonmotor symptoms of
      Parkinson disease (PD). Recently, awareness of sleep disorders related to PD has
      increased, reflecting their significant negative impact on the quality of life of
      the patient. However, sleep disturbances are still often under-recognized. In PD,
      multiple factors are associated with sleep disturbances; impaired arousal systems
      and sleep structure as disease-related changes, nocturnal motor symptoms,
      hallucinations and psychosis, pain, nocturia, depressive symptoms and
      dopaminergic medication can all cause insomnia. Further, these factors can
      coexist and influence each other during the course of the disease. In addition,
      sleep-related breathing disorder, restless legs syndrome (RLS) and rapid eye
      movement sleep behavior disorder (RBD) can also lead to impaired sleep. Some
      idiopathic RBD patients have been associated with a risk for developing
      neurodegenerative diseases, including PD. Therefore, early diagnosis of RBD may
      have significant clinical implications for neuroprotective strategies. Several
      studies have revealed an increased incidence of RLS in PD patients compared to
      the general population. The favorable responses to dopaminergic medications in
      treating both RLS and PD suggest shared pathophysiologies between the two
      diseases; however, neuroimaging studies of dopaminergic systems remain
      inconclusive. In this review, we discuss the current understanding of sleep
      disturbances in PD and the existing treatments.

PMID- 22481508
TI  - [Olfactory dysfunction in Parkinson disease and REM sleep behavior disorder].
AB  - Olfactory dysfunction is an appealing biomarker for Parkinson disease (PD)
      because of the high prevalence (>90%) among PD patients and the relative ease of
      testing, as compared to other putative biomarkers such as neuroimaging of the
      dopamine system. Hyposmia develops during the early stages of PD and, therefore,
      may be one of the most sensitive markers for the early diagnosis of PD. Sniffin'
      Sticks, the University of Pennsylvania Smell Identification Test, and the Odor
      Stick Identification test for the Japanese, a short and simple nonlexical,
      olfactory identification test, can be useful for diagnosing PD and for
      discriminating between PD and other parkinsonian syndromes. REM sleep behavior
      disorder (RBD) is indicative of the development of neurodegenerative diseases
      involving synuclein pathology, including PD, multiple system atrophy, and
      dementia with Lewy bodies (DLB). Reduced odor identification was comparable in
      patients with PD, DLB, and RBD, but distinct from that in healthy subjects.
      Further, insights obtained from a deeper understanding of the pathophysiology of
      olfactory dysfunction in PD and RBD may lead to a deeper understanding of the
      mechanism underlying Lewy neurodegenerative diseases.

PMID- 22481509
TI  - [Pain and sensory disturbance in Parkinson disease].
AB  - Pain or sensory symptoms are a frequent complaint in Parkinson disease (PD),
      which reduce health-related quality of life (QOL) and interfere with patient's
      ability to participate in activities of daily living, thus contributing to sleep
      disturbance or major depression. The frequency of pain is thought to have a
      bimodal distribution. The initial peak seems to occur before, or at the onset of
      PD and a second peak occurs later in the disease course in conjunction with the
      development of motor fluctuations or dyskinesia. The spectrum of sensory symptoms
      is wide, and the most common sites that experience pain are the back, legs, and
      shoulders. In cases, pain occurs on the side that is more affected by
      parkinsonism; however unusual distributions, such as oral or genital pain
      syndrome, chest pain, and upper or lower abdominal discomfort may be observed.
      The etiological basis of PD-related pain is multifactorial, with varying degrees
      of contribution from peripheral and central sources. Central mechanisms include
      derangement of the intrinsic pain-modulating monoaminergic mechanism in addition
      to plastic central nervous system changes induced by chronic anti-parkinsonian
      medication. The importance of dopaminergic deficits as a causal factor in PD
      related pain is supported by the normalization of these abnormalities after L
      dopa administration, which suggests that the human striatum plays a central role
      in processing nociceptive information. Nevertheless, the lack of response to
      dopaminergic agents in some patients suggests the involvement of non-dopaminergic
      structures in PD. Abnormalities of noradrenergic and serotonergic pathways
      descending to the spinal cord are assumed to play a role in pain perception in
      PD. Some reports have highlighted the problem of delayed diagnosis in PD patients
      with an initial presentation of pain. Greater awareness of this possibility among
      physicians is important. Physicians also should bear in mind that psychological
      factors are major components of pain and that patient education and support are
      critical to successful treatment.

PMID- 22481510
TI  - [Disinhibitory abnormal behavior induced by treatment of Parkinson disease].
AB  - The treatment of Parkinson disease has considerably progressed in the last 20
      years. However, such treatments results in the adverse event of disinhibitory
      abnormal behavior, which includes impulse control disorders, punding, and
      dopamine dysregulation syndrome. Pathological gambling is the most extensively
      studied among such abnormal behaviors. It has been associated with the use of
      dopamine agonists and its prevalence increases according to the does of the
      drugs. The maximum dose of the ergot dopamine agonist pergolide is 1.25 mg/day in
      Japan, which is a quarter of that used in Western countries. The maximum dose of
      the non-ergot dopamine agonist, pramipexole is 4.5 mg/day in Japan, which is the
      same as in Western countries. Pramipexole was launched in 2004 in Japan, and
      since then cases of pathological gambling associated with dopamine agonists used
      has been increasing. Because of the excellent health-care system in Japan,
      patients can easily acquire expensive dopamine agonists. Although the prevalence
      of these abnormal behaviors has not been studied in Japan, it could be highly
      proportionate to the amount of dopamine agonists. Disinhibitory abnormal behavior
      is also induced by deep brain stimulation of the subthalamic nucleus. This
      technology was approved in 2000 in Japan. The mechanisms by which these behaviors
      are induced are different between dopamine replacement therapy and deep brain
      stimulation. Parkinson disease patients and their caregivers occasionally believe
      the disinhibitory abnormal behavior as arising from the original personality of
      the patient rather than as an adverse event of treatment. Neurologists should be
      aware of the occurrence of disinhibitory abnormal behavior in the clinical
      practice.

PMID- 22481511
TI  - [Fatigue and weight loss in Parkinson's disease].
AB  - Fatigue is a common, under recognized, and poorly understood nonmotor symptom in
      Parkinson's disease (PD). Fatigue frequently presents early in PD, and its
      prevalence increases with disease progression, affecting up to 60% of patients.
      Fatigue has a negative impact on quality of life. Fatigue is often associated
      with other nonmotor symptoms, including sleep disturbance, excessive daytime
      sleepiness, and depression. Only a few reports have been published on the
      treatment of fatigue in PD (methylphenidate, levodopa, and pramipexole). Further
      well-designed studies, including physiotherapy, are necessary to develop more
      effective treatments for PD-associated fatigue. A number of patients with PD lose
      weight because of loss of fat. However, the evolution and determinants of weight
      loss are not well established. Possible determinants of weight loss in PD include
      loss of appetite, impaired hand-mouth coordination, difficulty in chewing and
      dysphagia, nausea, intestinal hypomotility, and increased energy requirements
      because of muscular rigidity and involuntary movements. Noticeable weight gain
      has repeatedly been reported after subthalamic or pallidal deep brain
      stimulation. Because low body weight is associated with negative health effects
      and a poor prognosis, monitoring weight and nutritional status should be part of
      PD management.

PMID- 22481512
TI  - [Autonomic features in Parkinson disease].
AB  - Nonmotor symptoms such as autonomic and neuropsychiatric dysfunctions, are
      commonly seen in Parkinson disease (PD). Recent studies have shown that PD is
      accompanied by cardiac sympathetic denervation and constipation even in the early
      stage. Neuropathological studies confirmed changes in the cardiac sympathetic
      nerves and the gastrointestinal tract. These findings suggest that PD
      neuropathology may occur first in the peripheral autonomic pathways and extend to
      the central autonomic pathways, in agreement with the "Braak theory". This
      article will reviews the symptoms and pathophysiology of gastrointestinal
      dysfunction, urinary disturbance, sexual dysfunction, sweating dysfunction,
      pupillary autonomic dysfunction, and orthostatic and postprandial hypotension in
      PD patients, and discuss to organ selectiveness in autonomic dysfunction in PD.

PMID- 22481513
TI  - [The clinical significance of MIBG myocardial scintigraphy in Parkinson disease].
AB  - Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy can assess postganglionic
      presynaptic cardiac sympathetic nerve endings. Reduced cardiac MIBG uptake on
      MIBG myocardial scintigraphy has been reported in patients with Parkinson disease
      (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and familial
      PD linked to SNCA duplication. This imaging procedure is a sensitive diagnostic
      tool that might differentiate PD and DLB from other movement disorders from
      Alzheimer disease (AD). We recently reported cardiac sympathetic denervation in
      PD, DLB, PAF, and familial PD linked to SNCA duplication which accounts for the
      reduced cardiac MIBG uptake in these disorders. The patients with PD, DLB, PAF
      and familial PD linked to SNCA duplication have Lewy bodies in the nervous
      system, whereas patients with multiple system atrophy (MSA), progressive
      supranuclear palsy (PSP), corticobasal degeneration, AD, and parkin-associated PD
      do not. However, in patients with MSA or PSP, cardiac sympathetic denervation was
      associated with the presence of Lewy bodies in the nervous system. Therefore,
      cardiac sympathetic denervation is closely related to the presence of Lewy bodies
      in the wide range of neurodegenerative processes. Thus, we conclude that reduced
      cardiac MIBG uptake is a potential biomarker for the presence of Lewy bodies in
      the nervous system. We infer that MIBG myocardial scintigraphy is a noninvasive
      tool for detecting Lewy bodies during life.

PMID- 22481514
TI  - [Transcranial sonography findings in Parkinson's disease].
AB  - Interest in diagnostic biomarkers that improve identification of Parkinson's
      disease (PD) in the early stages has been recently increasing. Accurate diagnosis
      of PD is currently a challenge for clinical neurologists. In addition, recent
      advances in basic research towards neuroprotective strategies for PD are
      increasingly highlighting the need for diagnostic biomarkers that improve
      identification of PD in the early stages. As such, substantia nigra
      hyperechogenicity visualized by transcranial sonography (TCS) has gained
      increasing attention and has been implemented in PD diagnosis globally. As
      substantia nigra hyperechogenicity offers unique information supplementary to
      those provided by other neuroimaging techniques, and this echofeature is stable
      during the disease course, it is very helpful in early and differential diagnosis
      of PD. The pathophysiologic conditions underlying this echofeature are not fully
      understood; however, it maybe associated with increased amounts of iron. It
      should be reminded that there are several limitations in conducting TCS. The main
      limitation is that in Japanese subjects the rate of temporal bone window
      sufficient for an adequate sonographic analysis prominently decreases with
      advancing age, particularly in females. Another limitation is that measurements
      may vary between two laboratories. Therefore, investigators are required to
      generate their own reference values. Despite these limitations, TCS can be
      recommended as a useful technique for the diagnosis of PD owing to its fast and
      easy use, low cost, and noninvasive nature. This review summarizes the TCS
      technique, the typical findings, and their value in the diagnosis and
      differential diagnosis of PD.

PMID- 22481515
TI  - [Recent advances in imaging in Parkinson disease].
AB  - Despite recent knowledge on the pathophysiology of Parkinson disease, the precise
      and early diagnosis of this condition remains difficult. Advances in imaging
      techniques have enabled the assessment of in vivo structural, neurometabolic, and
      neurochemical changes in Parkinson disease, and their role as biomarkers have
      assumed greater importance in recent years. We presently review the various
      approaches with these imaging techniques for the study of Parkinson disease.
      Voxel-based morphometry studies with structural MRI showed a characteristic
      pattern of gray matter loss, and fluoro-2-deoxy-D-glucose-positron emission
      tomography (FDG-PET) studies have indicated latent network abnormalities in
      Parkinson disease. Moreover, radiotracer imaging with dopaminergic markers
      facilitates the assessment of pre- and postsynaptic nigro-striatal integrity, and
      other radiotracers have been used in the studies of nondopaminergic
      neurotransmitter systems, such as the cholinergic, noradrenergic, and
      serotonergic systems. These imaging techniques can be used to detect
      presymptomatic disease and to monitor disease progression. Thus, imaging data
      provide meaningful insights into the pathological process in Parkinson disease.

PMID- 22481516
TI  - [Electroencephalogram and event-related potential analyses in Parkinson disease].
AB  - This article reviews recent quantitative electroencephalogram (qEEG) and event
      related potential (ERP) analyses in Parkinson disease (PD). We reported the first
      qEEG evaluation in PD not only employing multiple logistic regression analysis
      but also estimating the distribution of qEEG changes (Serizawa K, et al: 2008).
      We calculated the spectral ratio, i.e., the sum of the power values in the alpha
      and beta waves divided by the sum of the values in the slow waves. The
      significant predictive variables in PD were the spectral ratios at all electrode
      locations except for the frontal pole. The PD patients presented diffuse slowing
      in the qEEG as compared with age-adjusted normal controls. We also assessed the
      relationship between the progression of PD and qEEG (Morita A, et al: 2009). At
      all electrode locations, the spectral ratio significantly decreased with the
      progression of PD. Moreover, we studied qEEG alterations in PD patients with
      executive dysfunction (ExD) (Kamei S et al: 2010) and cognitive impairment
      (Morita A, et al: 2011). An increase in slow waves was observed in the frontal
      and frontal-pole locations in patients with ExD and presented in all locations in
      those with dementia. A recent report showed that qEEG findings have the potential
      for use as a predictive biomarker for the incidence of dementia in PD (Klassen
      BT, 2011). QEEG analysis is thus not only useful as a tool for studying
      pathophysiological findings but also as a predictive biomarker for dementia. ERP
      is a also useful tool for the evaluation of neuropsychological impairments in PD.
      P3 is elicited by target in the classic oddball task. P3b findings in PD have
      shown inconsistent results, with certain studies showing no changes and others
      showing prolonged P3b latency, and decreases and increases in P3b amplitude.
      However, prolonged P3b latency in PD patients with dementia have been
      consistently observed. Visual cognitive dysfunction and facial expression
      recognition in PD have been recently assessed with ERP techniques. ERP has a high
      potential for use in the detailed evaluation of cognitive dysfunction in PD.

PMID- 22481517
TI  - [Braak's hypothesis and non-motor symptoms of Parkinson disease].
AB  - In this review, we discuss dementia, depression, olfactory disturbance, sleep
      disorders and autonomic dysfunction as nonmotor symptoms of Parkinson disease
      (PD). PD with dementia (PDD) is defined as onset of dementia more than 1 year
      after the onset of parkinsonism. If dementia precedes or occurs less than 1 year
      after the onset of parkinsonism, a diagnosis of dementia with Lewy bodies (DLB)
      is made. There is essentially no difference in the pathology of PDD and DLB at
      autopsy, indicating that Braak's hypothesis, which is extracted from PD/PDD and
      excluding DLB, may be bias. REM-related behavioral disorder (RBD) or depression,
      the main locus of which is the brain stem, could precede or occur after the onset
      of PD or DLB, indicating a descending and ascending path of Lewy body (LB)
      pathology. A disturbance in olfaction usually precedes the onset of PD. Recent
      data indicate that severe olfactory dysfunction in PD is an indication of a high
      probability of mental decline. These clinical observations and our pathological
      reports support the presence of an olfactory-amygdala extension path of LB
      pathology in addition to Braak's hypothesis. Our pathological studies of
      consecutive autopsy cases showed that the involvement of autonomic ganglia was
      more frequent than that of the gastrointestinal tract, suggesting that initial
      the stage of LB pathology in Braak's hypothesis should be modified.

PMID- 22481518
TI  - [Does early detection of non-motor symptoms facilitate early treatment of
      Parkinson's disease?].
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder.
      The risk of developing of PD increases with age, it is estimated that the
      prevalence rate is approximately 150/100,000 in Japan. Recently, non-motor
      symptoms such as anosmia, autonomic failure, sleep disorders, sensory problems,
      depression, anxiety, cognitive disorders (including dementia), and psychosis are
      interested in the pathogenetic process of PD. According to the Braak's
      hypothesis, these non-motor symptoms precede the onset of the classic motor
      symptoms of PD. Many studies have shown that the number of neurons in the
      substantia nigra is decreased to approximately -40 to -60% in number when the
      motorsymptoms of PD are developed. In this article, review of special references
      regarding the natural history of PD shows that non-motor symptoms are the
      prodromal signs of PD. If disease modification therapy and/or disease prevention
      therapy is approved in the future, an early and accurate diagnosis of PD is
      needed. Accurate early diagnostic biomarkers including symptoms, some compounds,
      and radiological markers need to be identified.

PMID- 22481519
TI  - [Corticobasal syndrome: recent advances and future directions].
AB  - Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder
      described by Rebeiz et al. It is characterized by progressive, asymmetric,
      cortical (eg, apraxia, alien limb phenomena, cortical sensory loss, and
      myoclonus), and extrapyramidal (eg, rigidity, bradykinesia, dystonia, and tremor)
      dysfunction. However, CBD has many clinical phenotypes, and the features used for
      predicting CBD have low sensitivity. Therefore, the term corticobasal syndrome
      (CBS) has been used to characterize such clinical features, whereas the term CBD
      is used to refer to the pathological disorder. The most frequent causes of CBS
      are CBD, followed by Alzheimer's disease, progressive supranuclear palsy,
      frontotemporal lobar degeneration with TDP-43 pathology (sporadic and familial),
      Pick's disease, Lewy body disease, frontotemporal lobar degeneration with fused
      in sarcoma-positive inclusions, Creutzfeldt-Jakob disease, and mutations in the
      microtubule-associated protein tau (MAPT) and progranulin (GRN) genes. The
      topography of neurodegeneration dictates the clinical syndrome not according to
      the underlying pathology. Researchers have attempted to develop fluid biomarkers
      or imaging analysis for diagnosing CBS. The aim of this review was to highlight
      recent advances in CBS diagnosis and discuss future directions.

PMID- 22481520
TI  - [Non-bifurcating cervical carotid artery: a case report].

PMID- 22481521
TI  - Molecular evidence to suggest the origin of a colonization: Drosophila subobscura
      in America.
AB  - The recent colonization of America by Drosophila subobscura represents a great
      opportunity for evolutionary biology studies. Knowledge of the populations from
      which the colonization started would provide an understanding of how genetic
      composition changed during adaptation to the new environment. Thus, a 793
      nucleotide fragment of the Odh (Octanol dehydrogenase) gene was sequenced in 66
      chromosomal lines from Barcelona (western Mediterranean) and in 66 from Mt.
      Parnes (Greece, eastern Mediterranean). No sequence of Odh fragment in Barcelona
      or Mt. Parnes was identical to any of those previously detected in America.
      However, an Odh sequence from Barcelona differed in only one nucleotide from
      another found in American populations. In both cases, the chromosomal lines
      presented the same inversion: O(7), and the Odh gene was located within this
      inversion. This evidence suggests a possible western Mediterranean origin for the
      colonization. Finally, the molecular and inversion data indicate that the
      colonization was not characterized by multiple reintroductions.

PMID- 22481522
TI  - Vasodilator effects of cromakalim and HA 1077 in diabetic rat aorta.
AB  - BACKGROUND: Impairment of the vasorelaxant responses have been reported in
      diabetes mellitus. In this study, the roles of the K(ATP) channel and rho kinase
      pathway were evaluated by using the K(ATP) channel opener cromakalim and Rho
      kinase inhibitor HA 1077 in diabetic rat aorta. METHODS: Adult male Wistar rats
      weighing (250-300 g) were divided into diabetic and control groups. Diabetes was
      induced by a single intraperitoneal injection of streptozotocin (STZ, 55
      mg/kg/i.p). RESULTS: Vasodilator responses induced by cromakalim (10(-7) to 10(
      3M)) and HA 1077 (10(-6) to 10(-4M)) were significantly less in diabetic rings
      compared with control rings (p <0.01). The decrease in the relaxant effect of
      cromakalim was more in endothelium-denuded rings compared to the endothelium
      intact rings (p <0.05). There were no significant differences between endothelium
      intact and non-intact rings in the presence of HA 1077. When two drugs were
      administered together, relaxation was significantly less than with seperate
      administration of each drug in the diabetic group (p <0.01). Pre-treatment with N
      omega-nitro-L-arginine methylester (L-NAME) (10(-6) to 10(-4 M)), an NO synthase
      inhibitor, significantly decreased the relaxant response to cromakalime and HA
      1077 in both the control and diabetic groups (p <0.05). CONCLUSIONS: These
      results suggest that the impaired relaxant effects were further decreased
      depending on K(ATP) channel activity but the effects of Rho-kinase enzyme
      inhibitors on relaxation responses were not significantly changed in diabetes
      mellitus.

PMID- 22481523
TI  - The combination of a polymer-carbon composite electrode with a high-absorptivity
      ruthenium dye achieves an efficient dye-sensitized solar cell based on a thiolate
      disulfide redox couple.
AB  - To overcome the intrinsic shortcomings of the traditional iodide-triiodide redox
      couple and pursue a further performance improvement, intense efforts have been
      made to exploit alternative redox shuttles in dye-sensitized solar cells (DSCs).
      Herein, we report an energetic and kinetic view of DSCs when the iodine
      electrolyte is substituted with its thiolate counterpart and identify that a
      conventional platinum counter electrode presents low catalytic activity for the
      thiolate electrolyte, featuring a high charge transfer resistance found at the
      platinized fluorine-doped tin oxide (FTO). We employ conductive carbon black with
      several polymers to fabricate highly active composite catalysts for thiolate
      regeneration. The use of a highly active conductive carbon black and polymerized
      3,4-ethylenedioxythiophene composition as a counter electrode combined with a
      high-absorptivity ruthenium dye C106 sensitized titania film has generated a DSC
      with an organic thiolated electrolyte, exhibiting an overall power conversion
      efficiency of 7.6% under AM1.5G full sunlight. 

PMID- 22481524
TI  - Assessment of trace-metal concentrations in Western Reef heron (Egretta gularis)
      and Siberian gull (Larus heuglini) from southern Iran.
AB  - The objective of the present study was to investigate the levels of heavy metals,
      namely, chromium, copper, cobalt, nickel, and iron, in Western Reef heron
      (Egretta gularis) (n = 15) and Siberian gull (Larus heuglini) (n = 15) to (1)
      compare metal concentrations between two bird species with different trophic
      level, molting pattern, and life strategy; (2) examine species- and sex-related
      variations in trace-metal accumulation; and (3) determine the significance
      between heavy-metal concentrations in kidney, liver, and pectoral muscle. Bird
      samples were collected from November to December 2010 throughout the Hara
      Biosphere Reserve, and heavy metals were assayed by using a Shimadzu AA 680 flame
      atomic absorption spectrophotometer; the results were given as MUg/g dry weight.
      Metal concentrations were different between the bird species as well as among
      bird tissues, but there was no difference (except chromium and iron in kidney)
      between sex (male vs. female). Mean levels in kidney of Western Reef heron and
      Siberian gull were chromium (0.96, 2.32 MUg/g), copper (6.31, 10.55 MUg/g),
      cobalt (0.12, 0.14 MUg/g), nickel (1.13, 1.32 MUg/g), and iron (37.92, 39.64
      MUg/g), respectively, whereas in liver they were chromium (1.05, 2.75 MUg/g),
      copper (8.93, 12.63 MUg/g), cobalt (0.09, 0.17 MUg/g), nickel (1.1, 2.27 MUg/g),
      and iron (34.03, 44.21 MUg/g), respectively. Results showed that heavy-metal
      concentrations in Western Reef heron were decreased in the sequence iron > copper
      > nickel > chromium > cobalt, whereas in Siberian gull they were decreased in the
      sequence iron > copper > chromium > nickel > cobalt. Results also showed that in
      both species, the highest chromium and nickel concentrations were measured in
      female birds and the lowest in male birds, whereas the highest copper, cobalt,
      and iron (except iron in liver) concentrations were measured in male birds and
      the lowest in female birds.

PMID- 22481525
TI  - Bioaccumulation and toxicodynamics of cadmium to freshwater planarian and the
      protective effect of N-acetylcysteine.
AB  - Although toxic responses of freshwater planarians after exposure to environmental
      toxicants can be observed through external toxicological end points,
      physiological responses inside the bodies of treated planarians have rarely been
      investigated. The present study was designed, using cadmium (Cd) as a reference
      toxicant, to determine its bioaccumulation and toxicodynamics in the freshwater
      planarian, Dugesia japonica, after acute toxicity was obtained. Accumulated Cd
      concentrations, metallothionein levels, and the oxidative status in planarians
      were determined after exposure to Cd. Furthermore, we hypothesized that the acute
      death of Cd-treated planarians was associated with increased oxidative stress.
      After Cd-treated planarians were coexposed to antioxidant, N-acetylcysteine
      (NAC), we found that NAC protected planarians from Cd lethality by maintaining
      the oxidative status and decreasing the bioaccumulation of Cd. The results of the
      present study support planarians being used as a practical model for
      toxicological studies of environmental contaminants in the future.

PMID- 22481526
TI  - Nano-fabrication with a flexible array of nano-apertures.
AB  - We report fabrication and use of a flexible array of nano-apertures for
      photolithography on curved surfaces. The batch-fabricated apertures are formed of
      metal-coated silicone tips. The apertures are formed at the end of the silicone
      tips by either electrochemical etching of the metal or plasma etching of a
      protective mask followed by wet chemical etching. The apertures are as small as
      250 nm on substrates larger than several millimeters. We demonstrate how the nano
      aperture array can be used for nano-fabrication on flat and curved substrates,
      and show the subsequent fabrication steps to form large arrays of sub-micron
      aluminum dots or vertical silicon wires.

PMID- 22481527
TI  - RGB marking with lentiviral vectors for multicolor clonal cell tracking.
AB  - Cells transduced with lentiviral vectors are individually marked by a highly
      characteristic pattern of insertion sites inherited by all their progeny. We have
      recently extended this principle of clonal cell marking by introducing the method
      of RGB marking, which makes use of the simultaneous transduction of target cells
      with three lentiviral gene ontology (LeGO) vectors encoding red, green or blue
      fluorescent proteins. In accordance with the additive color model, individual RGB
      marked cells display a large variety of unique and highly specific colors. Color
      codes remain stable after cell division and can thus be used for clonal tracking
      in vivo and in vitro. Our protocol for efficient RGB marking is based on
      established methods of lentiviral vector production (3-4 d) and titration (3 d).
      The final RGB-marking step requires concurrent transduction with the three RGB
      vectors at equalized multiplicities of infection (1-12 h). The initial efficiency
      of RGB marking can be assessed after 2-4 d by flow cytometry and/or fluorescence
      microscopy.

PMID- 22481528
TI  - Highly multiplexed and strand-specific single-cell RNA 5' end sequencing.
AB  - Single-cell analysis of gene expression is increasingly important for the
      analysis of complex tissues, including cancer, developing organs and adult stem
      cell niches. Here we present a detailed protocol for quantitative gene expression
      analysis in single cells, by the sequencing of mRNA 5' ends. In all, 96 cells are
      lysed, and their mRNA is converted to cDNA. By using a template-switching
      mechanism, a bar code and an upstream primer-binding sequence are introduced
      simultaneously with reverse transcription. All cDNA is pooled and then prepared
      for 5' end sequencing, including fragmentation, adapter ligation and PCR
      amplification. The chief advantage of this approach is the great reduction in
      cost and time, afforded by the early bar-coding strategy. Compared with previous
      methods, it is more suitable for large-scale quantitative analysis, as well as
      for the characterization of transcription start sites, but it is unsuitable for
      the detection of alternatively spliced transcripts. Sample preparation takes 3 d,
      and two sets of 96 cells can be prepared in parallel. Finally, the sequencing and
      data analysis can take an additional 4 d altogether.

PMID- 22481529
TI  - Microfluidic single-cell real-time PCR for comparative analysis of gene
      expression patterns.
AB  - Single-cell quantitative real-time PCR (qRT-PCR) combined with high-throughput
      arrays allows the analysis of gene expression profiles at a molecular level in
      approximately 11 h after cell sample collection. We present here a high-content
      microfluidic real-time platform as a powerful tool for comparatively
      investigating the regulation of developmental processes in single cells. This
      approach overcomes the limitations involving heterogeneous cell populations and
      sample amounts, and may shed light on differential regulation of gene expression
      in normal versus disease-related contexts. Furthermore, high-throughput single
      cell qRT-PCR provides a standardized, comparative assay for in-depth analysis of
      the mechanisms underlying human pluripotent stem cell self-renewal and
      differentiation.

PMID- 22481530
TI  - Fabrication of functional three-dimensional tissues by stacking cell sheets in
      vitro.
AB  - The fabrication of 3D tissues retaining the original functions of tissues/organs
      in vitro is crucial for optimal tissue engineering and regenerative medicine. The
      fabrication of 3D tissues also contributes to the establishment of in vitro
      tissue/organ models for drug screening. Our laboratory has developed a
      fabrication system for functional 3D tissues by stacking cell sheets of confluent
      cultured cells detached from a temperature-responsive culture dish. Here we
      describe the protocols for the fabrication of 3D tissues by cell sheet
      engineering. Three-dimensional cardiac tissues fabricated by stacking cardiac
      cell sheets pulsate spontaneously, synchronously and macroscopically. Via this
      protocol, it is also possible to fabricate other tissues, such as 3D tissue
      including capillary-like prevascular networks, from endothelial cells sandwiched
      between layered cell sheets. Cell sheet stacking technology promises to provide
      in vitro tissue/organ models and more effective therapies for curing tissue/organ
      failures.

PMID- 22481531
TI  - Construction, expression and refolding of a bifunctional fusion protein
      consisting of C-terminal 12-residue of hirudin-PA and reteplase.
AB  - To obtain a bifunctional protein simultaneously showing bioactivity of
      anticoagulant and fibrinolytic for use in the treatment of thrombotic diseases,
      we constructed a fusion protein (HV12p-rPA) containing C-terminal 12-residue of
      hirudin-PA (HV12p) and reteplase (rPA). The fusion protein, in which HV12p was
      linked to rPA via Gly-Gly-Gly, was successfully expressed in an inactive form of
      inclusion bodies in Escherichia coli. HV12p-rPA was identified by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis. The expression level of HV12p
      rPA was optimized by an orthogonal method and finally enhanced from 12 % to
      approximate 30 %. We also deeply investigated the condition of renaturation of
      HV12p-rPA, and the inactive protein was partly renatured through various
      conditions. The refolding efficacy of HV12p-rPA estimated by the recovery of
      fibrinolytic activity varied from 0.03 % to 16.6 % and the anticoagulant activity
      fluctuated in the range from 41 to 2,297 ATU/mg. Bioassays indicated that the
      resulted fusion protein, as expected, exhibited both fibrinolytic and
      anticoagulant activities. These works laid a foundation for further
      characterization of HV12p-rPA.

PMID- 22481532
TI  - Fluorescence studies on the stability, flexibility and substrate-induced
      conformational changes of acetate kinases from psychrophilic and mesophilic
      bacteria.
AB  - The acetate kinase from the Antarctic psychrophilic Shewanella sp. AS-11 (SAK)
      has a significantly higher catalytic efficiency at low temperatures when compared
      with that from mesophilic Escherichia coli K-12 (EAK). To examine the stability
      and conformational flexibility of SAK and EAK, steady state intrinsic
      fluorescence studies were performed. EAK contains only one Trp at a position 46,
      while SAK contains two Trps at positions 46 and 388. From the fluorescence
      emission spectra, quenching with acrylamide, Cs(+) and I(-) at different
      temperatures and denaturation with guanidine-HCl, it was revealed that the SAK
      bears more flexible and unstable structure than that of EAK. Substrate-induced
      conformational changes reflect that SAK reached transition state through more
      conformational changes than EAK. In combination of our thermodynamic studies on
      the enzymatic reaction and present research findings, it can be concluded that
      these structural features of SAK may contribute to its high catalytic efficiency
      at low temperatures.

PMID- 22481533
TI  - Tight-binding description of Landau levels of graphite in tilted magnetic fields.
AB  - The electronic structure of Bernal-stacked graphite subject to tilted magnetic
      fields is studied theoretically. The minimal nearest-neighbor tight-binding model
      with the Peierls substitution is employed to describe the structure of Landau
      levels. We show that, while the orbital effect of the in-plane component of the
      magnetic field is negligible for massive Dirac fermions in the vicinity of the K
      point of the graphite Brillouin zone, at the H point it leads to the
      experimentally observable splitting of Landau levels, which grows approximately
      linearly with the in-plane field intensity.

PMID- 22481534
TI  - A first-principles prediction of two-dimensional superconductivity in pristine
      B2C single layers.
AB  - Based on first-principles lattice dynamics and electron-phonon coupling
      calculations, B(2)C sheets are predicted to be a two-dimensional (2D) phonon
      mediated superconductors with a relatively high transition temperature (T(c)).
      The electron-phonon coupling parameter was calculated to be 0.92 and it is mainly
      contributed by low frequency out-of-plane phonon modes and electronic states with
      a pi character. When the Coulomb pseudopotential, MU*, is set to 0.10, the
      estimated temperature, T(c), is 19.2 K. To the best of our knowledge, B(2)C is
      the first pristine 2D superconductor with a T(c) higher than the boiling point of
      liquid helium.

PMID- 22481535
TI  - Effect of laughter on salivary flow rates and levels of chromogranin A in young
      adults and elderly people.
AB  - OBJECTIVES: Salivary chromogranin A (CgA) levels and salivary flow rates were
      measured to evaluate the stress relief effect of laughter on the young and the
      elderly. METHODS: Thirty healthy volunteers (15 aged  20-25 years; 15 aged 62-83
      years) performed a serial arithmetic task for 15 min and then watched a comedy
      video for 30 min. On a different day, as a control, they watched a non-humorous
      video after performing a task similar to the first one. Saliva samples were
      collected immediately before and after the arithmetic task, 30 min after
      completing the task (immediately after watching the film), and 30 min after
      watching the film (60 min after completing mental task). Salivary CgA levels were
      determined by enzyme-linked immunosorbent assay. RESULTS: In the elderly group,
      salivary flow rates, which had declined by the end of the arithmetic task, were
      statistically significantly higher after watching the comedy video. In the young
      group, salivary CgA levels, which had increased by the end of the task, had
      statistically significantly declined after watching the comedy video. No such
      post-task changes were apparent in control results; in the young group, there was
      a statistically significant interprotocol difference in salivary CgA levels.
      CONCLUSIONS: These findings suggest that laughter may relieve stress,
      particularly in the young people.

PMID- 22481536
TI  - Pressurized liquid extraction of coumarins from fruits of Heracleum leskowii with
      application of solvents with different polarity under increasing temperature.
AB  - Coumarins are nowadays an important group of organic compounds from natural
      sources that are useful in a number of fields. Because they possess different
      pharmacological properties, finding the proper extraction conditions for their
      separation from plant matrices is a very important step. In this report
      Pressurized Liquid Extraction (PLE) under different temperature conditions and
      with different types of extraction solvents were tested. As a matrix, fruits of
      Heracleum leskowii have been used. A simple reverse phase high-performance liquid
      chromatographic method (RP-HPLC) coupled with a photodiode array detector (DAD)
      has been developed for separation and quantitative analysis of the main
      coumarins. Umbelliferone, xanthotoxin, angelicin, isopimpinellin, bergapten,
      imperatorin and isoimperatorin were investigated. Bergapten and imperatorin were
      dominant in almost all extracts in the range of 9.92 +/- 0.02-20.93 +/- 0.06 and
      12.19 +/- 0.98-19.07 +/- 0.03 mg/100 g, respectively. Dichloromethane and
      methanol were chosen as the most proper suitable solvents for extraction of
      coumarins. By increasing the temperature the amount of extracted coumarins
      increases in petroleum ether and dichloromethane extracts.

PMID- 22481538
TI  - Ionic liquid applications in peptide chemistry: synthesis, purification and
      analytical characterization processes.
AB  - This review aims to provide a comprehensive overview of the recent advances made
      in the field of ionic liquids in peptide chemistry and peptide analytics.

PMID- 22481537
TI  - Antioxidant, antitubercular and cytotoxic activities of Piper imperiale.
AB  - Phenolic compounds are widely distributed in Nature and act as pharmacologically
      active constituents in many herbal medicines. They have multiple biological
      properties, most notably antioxidant, antibacterial and cytotoxic activities. In
      the present study an attempt to correlate the phenolic composition of leaf,
      flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and
      cytotoxic activities was undertaken. The total phenol content ranged from 1.98 to
      6.94 mg GAE/gDW among ethanolic extracts, and gallic acid, catechin, epicatechin,
      ferulic acid, resveratrol and quercetin were identified and quantified by HPLC.
      DPPH and ABTS assays showed high antioxidant activity of the leaf extract
      (EC(50ABTS) = 15.6 ug/mL, EC(50DPPH) = 27.3 ug/mL) with EC50 in the same order of
      magnitude as the hydroxyquinone (EC(50ABTS) = 10.2 ug/mL, EC(50DPPH) = 15.7
      ug/mL). The flower extract showed strong antimicrobial activity against
      Mycobacterium tuberculosis H37Rv. All the extracts exhibited dose-dependent
      cytotoxic effects against MCF-7 cancer cells. This is the first time that a Piper
      extract has been found to be highly active against M. tuberculosis. This study
      shows the biological potential of Piper imperiale extracts and gives way to bio
      guided studies with well-defined biological activities.

PMID- 22481539
TI  - Synthetic study on the relationship between structure and sweet taste properties
      of steviol glycosides.
AB  - The structure activity relationship between the C16-C17 methylene double bond on
      the aglycone of steviol glycosides and the corresponding impact on their sweet
      taste has been reported here for the first time. It has been observed that
      converting stevioside and rebaudioside A to their corresponding ketones by
      switching the doubly bonded methylene on C-17 for a ketone group actually removes
      the sweet taste properties of these molecules completely. Regenerating the
      original molecules tends to restore the sweet taste of both the steviol
      glycosides. Thus this C16-C17 methylene double bond in rebaudioside A and
      stevioside can be regarded as a pharmacophore essential for the sweetness
      property of these molecules.

PMID- 22481540
TI  - (-)-Kunstleramide, a new antioxidant and cytotoxic dienamide from the bark of
      Beilschmiedia kunstleri gamble.
AB  - A new dienamide, (2E,4E)-7-(3',4'-dimethoxyphenyl)-N-ethyl-6-(R)-hydroxyhepta-
      2,4-dienamide, named (-)-kunstleramide (1), were isolated from the bark of
      Beilschmiedia kunstleri Gamble together with one neolignan: (+)-kunstlerone (2)
      and seven known alkaloids: (+)-nornuciferine (3), (-)-isocaryachine (4), (+)
      cassythicine (5), (+)-laurotetanine (6), (+)-boldine (7), noratherosperminine
      (8), (+)-N-demethylphyllocaryptine (9). Their structures were established from
      spectroscopic techniques, most notably 1D- and 2D-NMR, UV, IR, OR, circular
      dichroism (CD) spectra and LCMS-IT-TOF. (-)-Kunstleramide (1) exhibited very poor
      dose-dependent inhibition of DPPH activity, with an IC50 value of 179.5 +/- 4.4
      MUg/mL, but showed a moderate cytotoxic effect on MTT assays of A375, A549, HT
      29, PC-3 and WRL-68 with EC50 values of 64.65, 44.74, 55.94, 73.87 and 70.95
      ug/mL, respectively.

PMID- 22481541
TI  - Synthesis and NMR spectral studies of the 7-C60-adduct of n,n
      (tetrachlorophthaloyl) dehydroabietylamine.
AB  - The 7-C60-adduct of N,N-(tetrachlorophthaloyl)dehydroabietylamine was synthesized
      for the first time and characterized by IR, UV-vis, mass and NMR spectral
      studies. The 1H-NMR and 13C-NMR resonance signals of the new compound are
      unambiguously assigned by using homo- and heteronuclear 2D NMR spectroscopic
      techniques such as COSY, ROESY, HSQC and HMBC. The C1 symmetric structure with
      6,6-junction of compound was determined.

PMID- 22481542
TI  - A novel antioxidant isobenzofuranone derivative from fungus Cephalosporium
      sp.AL031.
AB  - Bioassay-guided fractionation of metabolites from the fungus Cephalosporium
      sp.AL031 isolated from Sinarundinaria nitida led to the discovery of a new
      isobenzofuranone derivative, 4,6-dihydroxy-5-methoxy-7-methylphthalide (1),
      together with three known compounds: 4,5,6-trihydroxy-7-methyl-1,3
      dihydroisobenzofuran (2), 4,6-dihydroxy-5-methoxy-7-methyl-1,3
      dihydroisobenzofuran (3) and 4,5,6-trihydroxy-7-methylphthalide (4). The
      structure of the new compound 1 was determined based on MS, 1D and 2D NMR
      spectral data. Compounds 1-4 showed potent antioxidant activity with EC50 values
      of 10, 7, 22 and 5 MUM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging
      assay.

PMID- 22481543
TI  - HCN channels and heart rate.
AB  - Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the
      molecular correlates of the "funny" pacemaker current (I(f)), a current activated
      by hyperpolarization and considered able to influence the sinus node function in
      generating cardiac impulses. HCN channels are a family of six transmembrane
      domain, single pore-loop, hyperpolarization activated, non-selective cation
      channels. This channel family comprises four members: HCN1-4, but there is a
      general agreement to consider HCN4 as the main isoform able to control heart
      rate. This review aims to summarize advanced insights into the structure,
      function and cellular regulation of HCN channels in order to better understand
      the role of such channels in regulating heart rate and heart function in normal
      and pathological conditions. Therefore, we evaluated the possible therapeutic
      application of the selective HCN channels blockers in heart rate control.

PMID- 22481544
TI  - Influence of cochlear implantation on the vestibular function.
AB  - The aim of the present study was to examine the influence of cochlear
      implantation on vestibular function. The function of the horizontal semicircular
      canal, the saccular function, and the incidence of vestibular symptoms were
      assessed before and after cochlear implantation. Twenty unilaterally cochlear
      implant patients were evaluated preoperatively, 1 and 6 months postoperatively,
      with caloric testing with electronystagmography (ENG) recordings and vestibular
      evoked myogenic potentials (VEMP) testing. A medical history was taken from every
      subject, noting the presence or absence of vertigo before and after the
      operation. A possible correlation between the appearance of postoperative vertigo
      and age, sex, implant side, preoperative caloric results and VEMP status, and
      postoperatively recorded changes in caloric and VEMP testing was also
      investigated. A statistically significant difference was found in the percentages
      of canal paresis (p = 0.01) and the percentages of VEMP waveform absence (p =
      0.002) between the repeated measurements in the implanted side, whereas in the
      non-implanted side no difference was (p > 0.05) found. Four patients complained
      of postoperative vestibular symptoms. In three of them the symptoms lasted less
      than 6 months postoperatively, but the fourth patient was still dizzy 6 months
      after cochlear implantation. No correlation was found between the above-mentioned
      factors and the occurrence of postoperative vertigo. In conclusion, although
      changes of the peripheral vestibular function of the implanted side were recorded
      in our patients, permanent vertigo was rare. Predictive factors for the
      occurrence of postoperative vestibular symptoms could not be identified.

PMID- 22481545
TI  - Device setting modifications for 3D flatpanel imaging in skull base surgery.
AB  - To evaluate the image quality and clinical implementation after setting
      modification of a three-dimensional isocentric C-arm fluoroscopic image
      intensifier system combined with a digital flatpanel detector as a new tool for
      sinus and petrous bone surgery. Image acquisition was performed using two
      cadaveric heads. Experimental design was oriented to the clinically sensible
      intraoperative setup. Different tube currents and orbital movements of the C-arm
      system were evaluated for image quality by three otolaryngological surgeons using
      predetermined landmarks. Modification of the X-ray intensity did not attain
      statistically significant values compared to the X-ray-intensity predetermined by
      producer (12.0-18.5 mA, p > 0.05) for either sinus or for petrous bone scans.
      Elliptical orbital movement resulted in significantly superior image quality than
      data sets acquired by circular orbital movement (3.194 vs. 2.809, p < 0.0001).
      New C-arm systems with 3D-capabiltity offer a promising tool for intraoperative
      near real-time image guidance. Image quality of the skull base can be improved
      significantly with optimized system settings.

PMID- 22481546
TI  - [Genetics of pheochromocytoma].
AB  - About one third of all patients with a pheochromocytoma are carriers of germ line
      mutations of 1 of the 10 susceptibility genes. Thus, these patients can be
      diagnosed and classified with specific tumor syndromes. This group is composed of
      the entities of multiple endocrine neoplasia type 2 (MEN2) due to mutations in
      the RET gene, von Hippel-Lindau disease (VHL, VHL gene), the paraganglioma
      syndromes types 1-4 (PGL1-4) due to mutations of the genes SDHD, SDHAF2, SDHC,
      SDHB, neurofibromatosis type 1 (NF1) due to mutations of the NF1 gene and
      familial pheochromocytoma syndromes due to mutations of the SDHA, TMEM127 and MAX
      genes. Patients with hereditary pheochromocytomas run a lifelong risk of relapse
      of pheochromocytoma. In addition extraparaganglial tumors are frequent and
      include medullary thyroid carcinoma in MEN2 or renal cancer or neuroendocrine
      pancreatic cancer as well as hemangioblastomas of the retina and the central
      nervous system in VHL. Furthermore, renal cancer may be associated with PGL4 and
      PGL3. In conclusion, molecular genetic screening is essential for the diagnosis
      of pheochromocytoma-associated cancer syndromes and is thus the cornerstone for
      successful lifelong preventive medicine of such patients and their relatives.

PMID- 22481547
TI  - Accuracy of CT-based attenuation correction in PET/CT bone imaging.
AB  - We evaluate the accuracy of scaling CT images for attenuation correction of PET
      data measured for bone. While the standard tri-linear approach has been well
      tested for soft tissues, the impact of CT-based attenuation correction on the
      accuracy of tracer uptake in bone has not been reported in detail. We measured
      the accuracy of attenuation coefficients of bovine femur segments and patient
      data using a tri-linear method applied to CT images obtained at different kVp
      settings. Attenuation values at 511 keV obtained with a (68)Ga/(68)Ge
      transmission scan were used as a reference standard. The impact of inaccurate
      attenuation images on PET standardized uptake values (SUVs) was then evaluated
      using simulated emission images and emission images from five patients with
      elevated levels of FDG uptake in bone at disease sites. The CT-based linear
      attenuation images of the bovine femur segments underestimated the true values by
      2.9 +/- 0.3% for cancellous bone regardless of kVp. For compact bone the
      underestimation ranged from 1.3% at 140 kVp to 14.1% at 80 kVp. In the patient
      scans at 140 kVp the underestimation was approximately 2% averaged over all bony
      regions. The sensitivity analysis indicated that errors in PET SUVs in bone are
      approximately proportional to errors in the estimated attenuation coefficients
      for the same regions. The variability in SUV bias also increased approximately
      linearly with the error in linear attenuation coefficients. These results suggest
      that bias in bone uptake SUVs of PET tracers ranges from 2.4% to 5.9% when using
      CT scans at 140 and 120 kVp for attenuation correction. Lower kVp scans have the
      potential for considerably more error in dense bone. This bias is present in any
      PET tracer with bone uptake but may be clinically insignificant for many imaging
      tasks. However, errors from CT-based attenuation correction methods should be
      carefully evaluated if quantitation of tracer uptake in bone is important.

PMID- 22481548
TI  - The bothersomeness of patient self-rated "complications" reported 1 year after
      spine surgery.
AB  - PURPOSE: The last few decades have witnessed a paradigm shift in the assessment
      of outcome in spine surgery, with patient-centred questionnaires superseding
      traditional surgeon-based assessments. The assessment of complications after
      surgery and their impact on the patient has not enjoyed this same enlightened
      approach. This study sought to quantify the incidence and bothersomeness of
      patient-rated complications 1 year after surgery. METHODS: Patients with lumbar
      degenerative disorders, operated with the goal of pain relief between October
      2006 and September 2010, completed a questionnaire 1 year postoperatively
      enquiring about complications arising as a consequence of their operation. They
      rated the bothersomeness of any such complications on a 5-point scale. Global
      outcome of surgery and satisfaction at the 12-month follow-up were also rated on
      5-point Likert scales. The multidimensional Core Outcome Measures Index (COMI)
      was completed preoperatively and at the 12-month follow-up. RESULTS: Of 2,282
      patients completing the questionnaire (92% completion rate), 687 (30.1%) reported
      complications, most commonly sensory disturbances (36% of those with
      complications) or ongoing/new pain (26%), followed by motor problems (8%), pain
      plus neurological disturbances (11%), and problems with wound healing (6%). The
      corresponding "bothersomeness" ratings for these were: 1% not at all, 23%
      slightly, 27% moderately, 31% very, and 18% extremely bothersome. The greater the
      bothersomeness, the worse the global outcome (Rho = 0.51, p < 0.0001), patient
      satisfaction (Rho = 0.44, p < 0.0001) and change in COMI score (Rho = 0.52, p <
      0.0001). CONCLUSION: Most complications reported by the patient are perceived to
      be at least moderately bothersome and hence are not inconsequential.
      Complications and their severity should be assessed from both the patient's and
      the surgeon's perspectives--not least to better understand the reasons for poor
      outcome and dissatisfaction with treatment.

PMID- 22481549
TI  - Kyphoplasty for lytic tumour lesions of the spine: prospective follow-up of 11
      cases from procedure to death.
AB  - BACKGROUND: The life span of cancer patients has improved due to advancements in
      cancer management. With long survival periods, more patients show metastatic
      disease. Osteolytic tumours of spine are generated by metastatic deposits or
      primary tumours of the spine. A prospective study was performed to evaluate the
      efficacy and safety of percutaneous kyphoplasty in patients with osteolytic
      tumours of the thoracic and lumbar spine. MATERIALS AND METHODS: Eleven patients
      (age range 52-77/average 65 years; 7 female, 4 male) with osteolytic tumours of
      the spine were treated with kyphoplasty. The main Tokuhashi score was registered
      preoperatively. Outcome was assessed prospectively by visual analogue scale (VAS)
      for pain, ECOG performance status, walking distance, standing and sitting time.
      RESULTS: Preoperative VAS (average 7.5; range 2.6-10) dropped to 3.0, 5 days
      postoperatively and remained below 5 for follow-up. Main Tokuhashi score was 6.3,
      ranging from 3 to 9. Survival time ranged from 2 to 293 (average 74.4) weeks.
      Average walking distance, standing and sitting time and ECOG performance score
      showed improvement. All patients returned home and no patient required re
      operation or readmission due to local disease progression or recurrence.
      CONCLUSION: Kyphoplasty is a suitable palliative treatment option for patients
      with advanced metastatic disease of the spine even with low Tokuhashi scores
      allowing rapid pain relief and mobilisation to increase the quality of life.

PMID- 22481550
TI  - Anterior thigh compartment syndrome after prone positioning for lumbosacral
      fixation.
AB  - We report a case of a patient who developed anterior thigh compartment syndrome
      after being positioned prone for instrumented lumbar spine surgery. Although
      rare, clinicians should be aware that compartment syndrome is a possible
      complication of spinal surgery.

PMID- 22481553
TI  - Severe heart failure and mechanical circulatory support.

PMID- 22481554
TI  - Congenital heart disease in the adult.

PMID- 22481555
TI  - Perioperative hypertensive crisis:  newer concepts.

PMID- 22481556
TI  - Cardiac tamponade.

PMID- 22481557
TI  - Robotic-assisted cardiac surgery.

PMID- 22481558
TI  - Cardiac electrophysiology procedures in clinical practice.

PMID- 22481559
TI  - The heart as an endocrine system.

PMID- 22481560
TI  - When cardiac patients need ECT--challenges for the anesthesiologist.

PMID- 22481561
TI  - Monitoring the patient at risk of hemodynamic instability in remote locations.

PMID- 22481562
TI  - Inflammatory diseases and the heart.

PMID- 22481564
TI  - Preface--cardiology for anesthesiologists.

PMID- 22481565
TI  - Social responsibility: a new paradigm of hospital governance?
AB  - Changes in modern societies originate the perception that ethical behaviour is
      essential in organization's practices especially in the way they deal with
      aspects such as human rights. These issues are usually under the umbrella of the
      concept of social responsibility. Recently the Report of the International
      Bioethics Committee of UNESCO on Social Responsibility and Health has addressed
      this concept of social responsibility in the context of health care delivery
      suggesting a new paradigm in hospital governance. The objective of this paper is
      to address the issue of corporate social responsibility in health care, namely in
      the hospital setting, emphasising the special governance arrangements of such
      complex organisations and to evaluate if new models of hospital management
      (entrepreneurism) will need robust mechanisms of corporate governance to fulfil
      its social responsiveness. The scope of this responsible behaviour requires
      hospitals to fulfil its social and market objectives, in accordance to the law
      and general ethical standards. Social responsibility includes aspects like
      abstention of harm to the environment or the protection of the interests of all
      the stakeholders enrolled in the deliverance of health care. In conclusion,
      adequate corporate governance and corporate strategy are the gold standard of
      social responsibility. In a competitive market hospital governance will be
      optimised if the organization culture is reframed to meet stakeholders' demands
      for unequivocal assurances on ethical behaviour. Health care organizations should
      abide to this new governance approach that is to create organisation value
      through performance, conformance and responsibility. 

PMID- 22481566
TI  - Knocking at the door of the unborn child: engineered nanoparticles at the human
      placental barrier.
AB  - Exposure of pregnant women and their unborn children to engineered nanoparticles
      (NPs) is not yet of major public concern. However, this may soon change in light
      of the ever-increasing production of NPs and the continuous appearance of novel
      NP-containing consumer products. However, NPs may not only pose risks to exposed
      individuals; they offer major potential for the development of novel therapeutic
      strategies to treat specifically either the mother or the developing foetus.
      Hence there is every reason to explore the transplacental transfer of engineered
      NPs in more detail, and to find answers to the vast number of open questions in
      this fascinating field of research.

PMID- 22481567
TI  - Can spin-polarized photoemission measure spin properties in condensed matter?
AB  - Photoemitted electrons move in a vacuum; their quantum state can be completely
      characterized in terms of energy, momentum and spin polarization by spin
      polarized photoemission experiments. A review article in this issue by Heinzmann
      and Dil (2012 J. Phys.: Condens. Matter 24 173001) considers whether the measured
      spin properties, i.e. the magnitude and direction of the spin polarization
      vector, can be traced back to the quantum state from which these electrons
      originate. The careful conclusion is that they can, which is highly relevant in
      view of the current interest in these experiments and their application to
      topological insulators, where the spin-orbit interaction produces spin-polarized
      surface states.

PMID- 22481569
TI  - Biological applications of magnetic nanoparticles.
AB  - In this review an overview about biological applications of magnetic colloidal
      nanoparticles will be given, which comprises their synthesis, characterization,
      and in vitro and in vivo applications. The potential future role of magnetic
      nanoparticles compared to other functional nanoparticles will be discussed by
      highlighting the possibility of integration with other nanostructures and with
      existing biotechnology as well as by pointing out the specific properties of
      magnetic colloids. Current limitations in the fabrication process and issues
      related with the outcome of the particles in the body will be also pointed out in
      order to address the remaining challenges for an extended application of magnetic
      nanoparticles in medicine.

PMID- 22481568
TI  - Functional screening of intracardiac cell transplants using two-photon
      fluorescence microscopy.
AB  - Although the adult mammalian myocardium exhibits a limited ability to undergo
      regenerative growth, its intrinsic renewal rate is insufficient to compensate for
      myocyte loss during cardiac disease. Transplantation of donor cardiomyocytes or
      cardiomyogenic stem cells is considered a promising strategy for reconstitution
      of cardiac mass, provided the engrafted cells functionally integrate with host
      myocardium and actively contribute to its contractile force. The authors
      previously developed a two-photon fluorescence microscopy-based assay that allows
      in situ screening of donor cell function after intracardiac delivery of the
      cells. This report reviews the techniques of two-photon fluorescence microscopy
      and summarizes its application for quantifying the extent to which a variety of
      donor cell types stably and functionally couple with the recipient myocardium.

PMID- 22481571
TI  - Impact of neighborhood social conditions and household socioeconomic status on
      behavioral problems among US children.
AB  - We examine the impact of neighborhood social conditions and household
      socioeconomic status (SES) on the prevalence of parent-reported behavioral
      problems among US children aged 6-17 years. The 2007 National Survey of
      Children's Health was used to develop a factor analytic index and a dichotomous
      measure of serious behavioral problems (SBP) in children. The outcome measures
      were derived from 11 items capturing parents' ratings of their children on a set
      of behaviors, e.g., arguing, bullying, and feelings of worthlessness, depression,
      and detachment. Dichotomous measures of perceived safety, presence of
      garbage/litter, poor/dilapidated housing, and vandalism were used to assess
      neighborhood social conditions. Household SES was measured using parental
      education and household poverty status. Logistic and least squares regression
      models were used to analyze neighborhood and household socioeconomic effects on
      the continuous and binary outcome measures after controlling for sociodemographic
      and psychosocial factors, including behavioral risk factors, family cohesion,
      social participation, and geographic mobility. Higher levels of behavioral
      problems were associated with socially disadvantaged neighborhoods and lower
      household SES. Adjusted logistic models showed that children in the most
      disadvantaged neighborhoods (those characterized by safety concerns, poor
      housing, garbage/litter in streets, and vandalism) had 1.9 times higher odds,
      children in poverty had 3.7 times higher odds, and children of parents with less
      than high school education had 1.9 times higher odds of SBP than their more
      advantaged counterparts. Improvements in neighborhood conditions and household
      SES may both help to reduce childhood behavioral problems.

PMID- 22481570
TI  - Tumor necrosis factor interaction with gold nanoparticles.
AB  - We report on a systematic investigation of molecular conjugation of tumor
      necrosis factor-alpha (TNF) protein onto gold nanoparticles (AuNPs) and the
      subsequent binding behavior to its antibody (anti-TNF). We employ a combination
      of physical and spectroscopic characterization methods, including electrospray
      differential mobility analysis, dynamic light scattering, polyacrylamide gel
      electrophoresis, attenuated total reflectance-Fourier transform infrared
      spectroscopy, fluorescence assay, and enzyme-linked immunosorbent assay. The
      native TNF used in this study exists in the active homotrimer configuration prior
      to conjugation. After binding to AuNPs, the maximum surface density of TNF is
      (0.09 +/- 0.02) nm(-2) with a binding constant of 3 * 10(6) (mol L(-1))(-1).
      Dodecyl sulfate ions induce desorption of monomeric TNF from the AuNP surface,
      indicating a relatively weak intermolecular binding within the AuNP-bound TNF
      trimers. Anti-TNF binds to both TNF-conjugated and citrate-stabilized AuNPs,
      showing that non-specific binding is significant. Based on the number of anti-TNF
      molecules adsorbed, a substantially higher binding affinity was observed for the
      TNF-conjugated surface. The inclusion of thiolated polyethylene glycol (SH-PEG)
      on the AuNPs inhibits the binding of anti-TNF, and the amount of inhibition is
      related to the number ratio of surface bound SH-PEG to TNF and the way in which
      the ligands are introduced. This study highlights the challenges in
      quantitatively characterizing complex hybrid nanoscale conjugates, and provides
      insight on TNF-AuNP formation and activity.

PMID- 22481572
TI  - Introduction to the special issue of articles from the 2007 National Survey of
      Children's Health.

PMID- 22481573
TI  - A silicon/zinc 2,9,16,23-tetraaminophthalocyanine coaxial core-shell nanowire
      array as an efficient solar hydrogen generation photocatalyst.
AB  - In this work, we have demonstrated that a silicon nanowire (SiNW) array can be an
      efficient visible light photocatalyst for hydrogen generation after being
      modified by the 2,9,16,23-tetraaminophthalocyanine of zinc (ZnTAPc). A
      photoelectrochemical (PEC) cell employing a ZnTAPc modified SiNW array as
      photoanode was found to be able to effectively produce hydrogen at a rate of 13
      umol (cm(2) h)(-1) under 100 mw cm(-2) irradiation from a xenon lamp. It is
      believed that the loading of ZnTAPc can enhance the efficiency of hydrogen
      generation and the stability of the SiNW array. This demonstrates that the ZnTAPc
      modified SiNW is a promising material for solar hydrogen generation.

PMID- 22481574
TI  - One-step entry to olefin-tethered N,S-heterocyclic carbene complexes of ruthenium
      with mixed ligands.
AB  - A series of Ru(II) mixed-ligand complexes RuBr(2)(PPh(3))(2)(N-AyBzTh) (Ay = prop
      2-enyl; BzTh = benzothiazol-2-ylidene) (4), RuBr(OAc)(PPh(3))(N-MeAyBzTh) (5),
      RuBr(OAc)(PPh(3))(N-MeBnBzTh)(2) (MeBn = 3-methylbut-2-enyl) (6) and
      RuCl(OAc)(PPh(3))(N-MeBnBzTh) (7) have been synthesized from
      Ru(OAc)(2)(PPh(3))(2) in one-pot condensation and ligand exchange reactions. X
      ray single-crystal diffraction analysis revealed that they are neutral octahedral
      Ru(II) complexes with one or two N,S-heterocyclic carbene (NSHC) ligands and a
      coordinated (4, 5 and 7) or dangling (6) olefin arm. The system displays a range
      of self-selecting structural variations. Entry of the hybrid olefin-NSHC and
      halide ligands ejects either one (5, 6 and 7) phosphine ligand or keeps both
      phosphines (4) by replacing the acetate. It is also possible to accommodate two
      NSHC ligands by keeping the olefin pendant (6). Complexes 5 and 7 are
      isostructural with all different ligands on the coordination sphere. Complexes 4
      6 are active towards transfer hydrosilylation showing good beta(Z) selectivity,
      with the Ru(II) bearing acetate giving higher yields.

PMID- 22481575
TI  - Protein expression, gene amplification, and mutational analysis of EGFR in triple
      negative breast cancer.
AB  - BACKGROUND: Although triple-negative breast cancer (TNBC) with epidermal growth
      factor receptor (EGFR) expression has been extensively studied, few studies have
      simultaneously examined EGFR expression and EGFR gene amplification. Here, we
      examined the correlations of EGFR expression with EGFR gene amplification, EGFR
      activating mutations, and the expression of components of the Akt pathway.
      METHODS: Tumor tissues were obtained from 84 patients with TNBC. We analyzed the
      expression of EGFR, phosphorylated Akt (p-Akt), phosphorylated mammalian target
      of rapamycin (p-mTOR), and other relevant proteins using immunohistochemistry. We
      also analyzed EGFR gene and chromosome 7 copy numbers by dual-color in situ
      hybridization. DNA was extracted from formalin-fixed paraffin-embedded samples.
      Analysis of EGFR gene-activating mutations was performed using the smart
      amplification process version 2 assay. RESULTS: Most TNBCs expressing EGFR are
      non-specialized invasive ductal carcinomas, whereas others are likely to be rare
      specialized carcinomas, such as typical medullary carcinoma, apocrine carcinoma,
      metaplastic carcinoma, and adenoid cystic carcinoma. EGFR was expressed in
      samples from 28 of 84 (33.3%) patients, but the EGFR gene was not amplified in
      any of the 84 samples. There were significant correlations between EGFR
      expression and the number of polysomic cells and the presence of high polysomy of
      chromosome 7. However, EGFR expression was not correlated with p-Akt or p-mTOR
      expression, nor with the other clinicopathological factors recorded in this
      study. We found no evidence of EGFR gene-activating mutations. CONCLUSIONS: EGFR
      gene amplification and EGFR-activating mutations might not be the mechanisms
      leading to the constitutive activation of EGFR in TNBC. Further investigation is
      needed to clarify the other molecular mechanisms for oncogenic activation of EGFR
      in TNBC.

PMID- 22481576
TI  - Dermoscopic criteria and basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most frequent of all skin cancers in the white
      population. Dermoscopy is a method that improves diagnosis in pigmented and non
      pigmented skin lesions, allowing early diagnosis, especially of incipient
      lesions. The classical dermoscopy algorithm for the diagnosis of BCC includes
      lack of pigment network and the presence of at least one of the following
      criteria: ulceration, maple-leaf like structure, blue-gray globules, blue-ovoid
      nests, arborizing vessels and spoke-wheel structures. The non-classical
      dermoscopic features of BCC include some criteria more frequently seen in
      superficial BCC such as pink-white areas, concentric structures, multiple
      erosions, multiple in-focus blue-gray dots and fine vessels. Recently, the
      dermoscopy of Fibroepithelioma of Pinkus has also been described with the
      presence of fine arborizing vessels, white streaks and gray-brown structureless
      areas. Some dermoscopic structures also present in BCC are just visible with
      polarized dermoscopy such as white shiny streaks or Chrysalides and Rosetas.
      Improved knowledge of all these criteria may avoid some diagnostic pitfalls and
      improve the early recognition of BCCs.

PMID- 22481577
TI  - Dermoscopic features of common nevi: a review.
AB  - The differentiation between benign and worrisome melanocytic lesions may be
      challenging in the absence of the glaringly obvious clinical features that define
      a cutaneous malignancy. In such situations, dermoscopy may prove useful in
      further defining characteristics that are more indicative of a benign lesion,
      which can ultimately help avoid an unnecessary biopsy. Recognizing of the
      dermoscopic findings of benign nevi, taking into consideration the predominant
      pigment pattern and its organization, may aid in the evaluation of pigmented
      lesions. Benign nevi tend to exhibit symmetry, regularity in shape, and
      uniformity of dermoscopic structures. This article reviews the clinical and
      dermoscopic features of common acquired nevi (dermal, compound, and junctional),
      blue nevi, and congenital nevi.

PMID- 22481578
TI  - Dermoscopic criteria and melanocytic lesions.
AB  - Dermoscopy is a noninvasive, in vivo method for the early diagnosis of malignant
      melanoma and the differential diagnosis of pigmented lesions of the skin. By
      allowing visualization of sub-macroscopic pigmented structures that correlate
      with specific underlying histopathologic structures, dermoscopy provides a more
      powerful tool than the naked-eye examination for clinicians to determine the need
      to excise a lesion. This article reviews the principles of dermoscopy, the most
      common dermoscopic patterns associated with nevi and melanoma, and the factors
      influencing the nevus pattern in a given individual.

PMID- 22481579
TI  - Chronic pruritus.
AB  - Chronic pruritus is one of the most frequent complaints of the skin associated
      with a high disease burden and markedly impaired quality of life. Chronic
      pruritus (>6 weeks of duration) may occur in a broad variety of diseases
      including dermatological, systemic, neurological, psychosomatic/psychiatric and
      gynaecological ones and in every age group (children, adults, pregnant women,
      elderly patients). The medical care of patients with chronic pruritus has
      improved significantly in the past few years (14). Though research into the
      neurobiology of chronic pruritus has failed to resolve the mechanisms underlying
      this disease, it has led to the awareness that management of patients with
      chronic pruritus needs a separate strategy that is different from therapy of the
      underlying disease. The antipruritic therapy is still based on symptomatic
      regimens and target-specific therapies urgently needed.

PMID- 22481580
TI  - Clinical applicability of in vivo reflectance confocal microscopy in dermatology.
AB  - In vivo reflectance confocal microscopy (RCM) is a non-invasive diagnostic
      technique that offers the evaluation of the skin at real time with cellular
      resolution. In the past decade, multiple studies have been performed showing the
      clinical applicability of RCM for the diagnosis of melanoma and non melanoma skin
      cancer (NMSC). In this regard, RCM has moved from a research tool to a valuable
      diagnostic technique being applied in daily clinical practice. In this regard,
      RCM aids in the diagnosis and differential diagnosis of various skin diseases and
      may also be used for selection of the biopsy site. Furthermore, RCM allows
      monitoring of a skin lesion over time without tissue alteration and thus
      represents a valuable method for treatment monitoring.

PMID- 22481581
TI  - Psoriasis and cardiovascular disorders.
AB  - There is considerable evidence to show that patients with moderate-to-severe
      psoriasis have a significantly increased risk of cardiovascular disease and
      cardiovascular risk factors such as obesity, diabetes mellitus, the metabolic
      syndrome and smoking compared to the general population. The mechanistic link
      between psoriasis and this observed increase in cardiovascular co-morbidities has
      not been fully defined. It is clear, however, that common inflammatory pathways
      are at play in the pathophysiology of psoriasis, obesity and coronary artery
      disease. It had been proposed that the control of systemic inflammation in
      psoriasis could help reduce cardiovascular morbidity, and retrospective studies
      of methotrexate and anti-TNF-a agents have suggested a cardio-protective effect
      with use of these agents. More recently, however, there have been concerns
      regarding a potential excess of cardiovascular events with the newer generation
      of anti-interleukin-12p40 antibodies. In this article we review the association
      of psoriasis with cardiovascular disorders and the effects of current psoriasis
      therapies on cardiovascular risk.

PMID- 22481582
TI  - Psoriasis and cardiovascular comorbidities with emphasis in Asia.
AB  - Psoriasis is traditionally considered a skin-specific disease with the exception
      of coexisting psoriatic arthritis. However, growing evidence suggests a link
      between psoriasis and other comorbidities. Cardiovascular comorbidity, in
      particular, is the focus of considerable research, due in part to the associated
      mortality and possible intervention. A common mechanism that may explain both
      psoriasis and atherosclerosis pathogenesis is of great interest and utility. The
      increase of Th1 and Th17 leading to chronic inflammation is thought to be a patho
      denominator for both diseases. In addition, progressive adiposity and resultant
      metabolic syndrome are but the beginning steps in the "psoriatic march". In this
      article, we review the recent publications on cardiovascular risks in patients
      with psoriasis. We also examine the effects of psoriasis treatment, including the
      new biologics, on cardiovascular comorbidities. Although there is generally a
      lack of Asian research on this issue, we present the most recent pertinent
      findings from Taiwan.

PMID- 22481583
TI  - "Cowboy's belt with revolver" scleroderma caused by vitamin K1 injections.
AB  - Vitamin K1 (phytomenadione or phytonadione) is a fat soluble vitamin used to
      treat certain coagulation disorders. Intra muscular injection of vitamin K1 can
      occasionally be complicated by different types of skin reactions: erythematous
      plaques, urticarial rashes or scleroderma-like lesions at the injection site. We
      report the case of a 52-year-old man presenting with 2 symmetrical erythematous
      infiltrated scleroderma-like plaques localized on the right and left lower trunk.
      To correct the coagulation deficiency with hypoprothrombinemia developed as a
      consequence of HCV+ hepatitis, the patient was on vitamin K1 therapy,
      administered by i.m. injection (10 mg Vitamin K1/1 ml) once a day for 2 weeks.
      Three months after treatment interruption, ivory indurated morphoeiform plaques
      developed at the injection sites, assuming the typical appearance of a "cowboy's
      belt with revolver". The scleroderma-like lesions persisted 2 years after vitamin
      K1 withdrawal. We report this case to highlight the possibility that vitamin K1
      injections can occasionally be complicated by different types of skin reactions
      such as sclerodermatous plaques. Due to the delay in the onset, to the variable
      clinical picture, to the persistence after therapy interruption, this kind of
      lesions can represent a tricky diagnostic challenge and in spite of different
      treatments can endure for years.

PMID- 22481584
TI  - Unusual localization of allergic contact dermatitis to p-phenylenediamine in a
      dye.

PMID- 22481585
TI  - Metastases of malignant melanoma to gastrointestinal tract: a rare event.

PMID- 22481586
TI  - Melanoma of unknown primary with nodal metastases, presenting with vitiligo-like
      depigmentation.

PMID- 22481587
TI  - AIDS: a dermatological diagnosis?

PMID- 22481588
TI  - Cutaneous lupus erythematosus of the scalp treated with methyl-aminolevulinate
      photodynamic therapy: a case report.

PMID- 22481589
TI  - Enhanced diagnosis of genital warts with videodermatoscopy: histopatologic
      correlation.

PMID- 22481590
TI  - A case of carpet beetle dermatitis.

PMID- 22481591
TI  - Sun exposure and development of basal cell carcinomas: comparison between 504
      patients affected by basal cell carcinoma and 475 non-affected.

PMID- 22481592
TI  - Langerhans cell histiocytosis with perianal localization.

PMID- 22481593
TI  - Grover's disease in a renal transplant patient, after hemodialysis renewal.

PMID- 22481594
TI  - Acne keloidalis nuchae on herpes zoster scar in an HIV patient: isotopic response
      or not?

PMID- 22481595
TI  - Evaluation of a novel in-vitro diagnostic device for the detection of urinary
      tract infections in diaper wearing children.
AB  - QUESTIONS: Is the novel in-vitro diagnostic device U-Test((r)) reliable and
      secure for urine collection in diaper-wearing children and simultaneous
      evaluation of the urine collected for the presence of leucocytes and nitrite?
      METHODS: The qualitative and functional performance of U-Test((r)) was evaluated
      in a multicentre prospective clinical trial. The diagnostic performance of the
      novel in-vitro diagnostic device was determined in reference to the established
      procedure involving urine sampling by urine-bag, clean-catch, catheterisation and
      suprapubic aspiration followed by dipstick analysis and urine culture, and in an
      in-vitro study. RESULTS: U-Test((r)) proved to be comfortable and secure for the
      child and well accepted by the persons responsible for the participating
      children. No undesired side-effects were seen and in 75.8% (95% CI +/- 10.5%; n =
      66) of the tests used, enough urine was collected within the permitted time for
      immediate and successful urine analysis by the integrated test card. Diagnostic
      performance was found to be comparable to the established procedure using
      dipstick analysis (leucocytes: kappa-coefficient 0.86; nitrite: kappa-coefficient
      0.74; n = 150). Sensitivity of the U-Test((r)) for leucocyte detection was found
      to be 96.7% and specificity 100.0%. For nitrite detection sensitivity of 90.0%
      and specificity of 98.3% were found. CONCLUSIONS: The evaluation shows that U
      Test((r)) is a safe and reliable device of high functionality and diagnostic
      performance for the detection of leucocytes and nitrite directly and without time
      delay in a child's diaper. This statement is based on a comprehensive comparison
      of the novel device with accepted diagnostic test systems and procedures based on
      the same dry chemistry technology. Due to its simplicity of use, U-Test((r)) can
      be considered an alternative to the cumbersome procedures of urine collection by
      the bag-method or clean-catch followed by dipstick analysis for the presence of
      leucocytes and nitrite.

PMID- 22481596
TI  - Study of PET intrinsic spatial resolution and contrast recovery improvement for
      PET/MRI systems.
AB  - This paper studied PET intrinsic spatial resolution and contrast recovery
      improvement for PET/MRI dual modality systems. A Monte Carlo simulation tool was
      developed to study positron diffusion in tissues with and without a magnetic
      field for six commonly used isotopes ((18)F, (11)C, (13)N, (15)O, (68)Ga and
      (82)Rb). A convolution process was implemented to investigate PET intrinsic
      spatial resolution, taking into account three factors: positron diffusion range,
      collinear photon annihilation and finite detector element width. The resolution
      improvement was studied quantitatively as a function of magnetic field strength
      for three PET system configurations (whole-body, brain-dedicated and small-animal
      PET). When the magnetic field strength increases up to 10 T, the system spatial
      resolution in directions orthogonal to the field for (15)O, (68)Ga and (82)Rb is
      comparable to that of (18)F without the magnetic field. Beyond 10 T, no
      significant improvement of spatial resolution was observed. In addition, the
      modulation transfer function was studied to predict the intrinsic contrast
      recovery improvement for several existing and promising PET/MRI configurations.

PMID- 22481597
TI  - Identification of quarries rehabilitation scenarios: a case study within the
      metropolitan area of Bari (Italy).
AB  - This paper addresses quarries rehabilitation issue within a Metropolitan Area.
      Areas where mining activity is carried out have been subjected to physical and
      environmental degradation linked both to pursue the building materials extraction
      and to the city expansion continuously asking for new areas to be developed with
      residential and service functions. These changes also occurred where
      environmental and landscape values are present. It has been therefore pointed out
      the issue of such areas redevelopment that, to be functionally reintegrated, must
      be consistently linked to the activities and the territorial local contexts
      characteristics. In this paper the quarries reuse issue is carried out through
      parameters identification able to define the quarries relationship with the
      neighboring towns and with their surroundings besides to identify their physical,
      environmental and landscaping characteristics. Quarry reuse alternatives have
      been identified among those consistent with the rehabilitation goals, as defined
      by the planning sector and internationally approved, while their selection is
      derived from the application of a two-step methodology: a multi-criteria analysis
      related to punctual parameters at a "site-specific" level, followed by a further
      territorial indicators checking over the wide area. This application has led to
      socially accepted results identifying the examined quarries for reuses ranging
      from agricultural-forestry and urban to functional or naturalistic. The proposed
      method has also proved to be suitable to address the abandoned quarries reuse
      problem with a systemic and consultative approach, as it is able to correlate the
      many variables present in the social and spatial complexity of the Metropolitan
      Areas.

PMID- 22481598
TI  - Quantitative analysis of myopic chorioretinal degeneration using a novel computer
      software program.
AB  - To quantify the fundus color on digital color fundus photographs as a surrogate
      of myopic chorioretinal degeneration in myopic subjects using a novel computer
      software program. In this cross-sectional study, the following details were
      recorded in 152 eyes of 78 myopic subjects: Snellen visual acuity, refractive
      status, ocular biometric parameters, intraocular pressure, color fundus
      photography, and myopic chorioretinal degeneration index (MCDI) using an
      automated computer program. The mean age of the subjects was 32.58 +/- 11.12
      years (range, 21-62 years). Subjects with aged >=40 years had a significantly
      higher MCDI when compared with subjects with aged <40 years (MCDI: age >= 40 =
      0.519; age < 40 = 0.462, P = 0.000). The MCDI demonstrated a statistically
      significant and positive relationship with axial length (r = 0.47, P = 0.000) and
      lens thickness (r = 0.26, P = 0.023). A significant positive relationship was
      observed between the MCDI and visual acuity (r = 0.30, P = 0.007). The MCDI
      represents an objective technique for quantitative assessment of chorioretinal
      degenerative changes in myopic subjects. Older myopic subjects with a relatively
      higher MCDI and longer axial length may represent a high-risk population who have
      an increased likelihood of developing visually consequential complications of
      myopia.

PMID- 22481599
TI  - Genetic variability and potential recombination events in the HC-Pro gene of
      sugarcane streak mosaic virus.
AB  - Sugarcane streak mosaic virus (SCSMV), a member of the family Potyviridae, is an
      important viral pathogen affecting sugarcane production in India. The variability
      in the nucleotide (nt) and amino acid (aa) sequences of helper component
      proteinase (HC-Pro) of SCSMV isolates from India was investigated and compared
      with those of previously published virus isolates from different Asian countries.
      Comparison of all of the sequenced virus isolates revealed a high level of
      diversity in the HC-Pro gene (72-97% nt sequence identity; 83-99% aa sequence
      identity), and the Indian isolates were found to be the most divergent (up to 12%
      variation at the amino acid level). Phylogenetic analysis revealed clustering of
      16 SCSMV isolates into two groups. Group I included isolates from India and
      Pakistan, and group II consisted of isolates from Japan and Indonesia.
      Recombination analysis revealed nine potentially significant recombination
      events, and putative recombination sites were identified throughout the HC-Pro
      gene. Analysis of selection pressure indicated that the HC-Pro gene of SCSMV is
      under strong negative selection. It is likely that recombination, along with
      strong negative selection, enhances the speed of elimination of deleterious
      mutations in the HC-Pro gene.

PMID- 22481600
TI  - Ratification vote on taxonomic proposals to the International Committee on
      Taxonomy of Viruses (2012).

PMID- 22481601
TI  - Steady-state pharmacokinetics of lopinavir plus ritonavir when administered under
      different meal conditions in HIV-infected Ugandan adults.
AB  - We investigated the effect of food on the steady-state pharmacokinetics of
      lopinavir and ritonavir in 12 Ugandan patients receiving lopinavir coformulated
      with ritonavir (LPV/r) tablets using a crossover design. Intensive
      pharmacokinetic sampling was performed 7 days apart after LPV/r dosing under
      moderate fat, high fat, and fasted meal conditions. Lopinavir and ritonavir
      concentrations were determined by liquid chromatography and tandem mass
      spectrometry. Compared with the fasted state, a high fat meal reduced lopinavir
      and ritonavir area under the curve by 14% and 29%, respectively. With a moderate
      fat meal, area under the curve for both drugs was similar to the fasted state.

PMID- 22481602
TI  - Ultrasensitive assessment of residual low-level HIV viremia in HAART-treated
      patients and risk of virological failure.
AB  - BACKGROUND: Low-level viremia (LLV) is measurable, with enhanced assays, in many
      subjects with HIV RNA levels <50 copies per milliliter. The clinical consequences
      of LLV are unknown. METHODS: In a prospective study in HIV-1-infected adults, HIV
      RNA levels were determined with an ultrasensitive test (3 copies/mL) based on a
      real time polymerase chain reaction. The primary end point was to evaluate LLV
      prediction of virological failure, defined as a confirmed plasma HIV RNA level
      >50 copies per milliliter. RESULTS: One thousand two hundred fourteen patients
      were followed for (mean) 378 days. At baseline, 71.5% were <3 copies per
      milliliter below the limit of detection (BLD). The risk of failing highly active
      antiretroviral therapy in the following 4 months for patients BLD was 0.4%
      compared with a 3.2% risk for those with LLV (P < 0.0001; odds ratio: 7.52).
      There was a significant (P < 0.0001) linear relationship between the HIV RNA and
      the risk of virologic failure. LLV receiver operating curve analysis showed an
      area under the curve of 0.76 (95% confidence interval: 0.68 to 0.84) that
      significantly (P < 0.0001) predicted the risk of failure. The risk of an
      unconfirmed viral blip was higher in patients with LLV (3.9%) than in those BLD
      (1.1%) (P < 0.0001; odds ratio: 3.56). Longer exposure to antiretrovirals,
      current use of nonnucleoside reverse transcriptase inhibitors, longer time BLD,
      and current HIV RNA <3 copies per milliliter were independent predictors of a
      positive outcome. INTERPRETATION: Viral replication may be the cause of LLV, at
      least in some patients. A LLV >3 copies per milliliter is linked to a significant
      increment of risk of virological failure leading to drug resistance. Patients
      with measurable LLV should be managed to better evaluate, over time, the risk of
      failure and to limit its consequences.

PMID- 22481604
TI  - Mother to child transmission of HIV--another complication of bacterial vaginosis?

PMID- 22481603
TI  - Identifying the HIV transmission bridge: which men are having unsafe sex with
      female sex workers and with their own wives or steady partners?
AB  - OBJECTIVE: To gain insights into bridging behaviors and their correlates among
      male clients of female sex workers (FSWs). METHODS: Men aged >=18 years who
      recently paid or traded for sex with FSWs were recruited in Tijuana in 2008-2009.
      Participants underwent interviews and testing for HIV, chlamydia, syphilis, and
      gonorrhea. Logistic regression compared "bridgers" (clients who had unprotected
      sex with FSWs and with a wife or steady partner) with men who did not. RESULTS:
      Of 383 men, 134 (35%) had a steady partner. Half (n = 70) of those had
      unprotected sex with both FSWs and the steady partner. Prevalence of any sexually
      transmitted infection or HIV was 16.5% among bridgers and 2.3% among nonbridgers.
      Compared with other clients, bridgers were more likely to use drugs during sex
      with FSWs (81.4% versus 46.9%, P < 0.0001), had higher sensation-seeking (P <
      0.0001) and misogyny scores (P = 0.05) and were more likely to offer FSWs extra
      money for unprotected sex (34.4% versus 1.6%, P < 0.0001). Factors independently
      associated with bridging were as follows: using drugs during sex with FSWs
      [adjusted odds ratio (AOR): 3.4, P = 0.007], sensation seeking (AOR: 4.3 per unit
      increase, P = 0.05), and offering FSWs more money for unprotected sex (AOR: 24.5,
      P = 0.003). CONCLUSION: Sensation-seeking clients who use drugs during sex and
      coerce FSWs into unprotected sex may be less responsive to standard risk
      reduction interventions. Interventions are needed that target clients rather than
      rely on FSWs to change behaviors that may not be under their control.

PMID- 22481605
TI  - Prevalence and correlates of HIV and HCV infection among amphetamine-type
      stimulant users in 6 provinces in China.
AB  - BACKGROUND: China has experienced an epidemic of amphetamine-type stimulant (ATS)
      use in recent years. The present study explored the status and correlates of HIV
      and hepatitis C virus (HCV) infection among ATS users in China. METHODS: A
      multicenter cross-sectional study of HIV and HCV status and associated behaviors
      among ATS users was conducted in 6 provinces from September 2009 to December
      2010. Socioeconomic/behavioral risk factors were measured. Blood samples were
      collected to test for HIV and HCV antibodies. RESULTS: Of the 1327 ATS users, the
      prevalence of HIV and exposure to HCV were 4.5% and 43.5%, respectively, with
      large geographic variations (0%-20.3% and 8.6%-67.1%, respectively). HIV
      infection was independently associated with living in Yunnan province [adjusted
      odds ratio = 15.8; 95% confidence interval (CI): 2.0 to 125.1), polydrug use
      (adjusted odds ratio = 2.6; 95% CI: 1.3 to 5.4), increased frequency of sexual
      behavior (adjusted odds ratio = 2.0; 95% CI: 1.1 to 4.1), history of sex with
      sexually transmitted infection-positive persons (adjusted odds ratio = 11.4; 95%
      CI: 1.3 to 98.9), and HCV infection (adjusted odds ratio = 2.8; 95% CI: 1.2 to
      6.7). HCV was associated with study site, marital status, unemployment (adjusted
      odds ratio = 1.8; 95% CI: 1.3 to 2.4), a longer duration of ATS use, and history
      of injection use of ATS (adjusted odds ratio = 13.3; 95% CI: 1.5 to 116.1).
      CONCLUSIONS: The prevalence of HIV was high among ATS users in Yunnan province
      but quite rare elsewhere, and the prevalence of exposure to HCV was high in 6
      provinces. Risk factors emphasize the need for new prevention strategies toward
      this population at risk in China.

PMID- 22481606
TI  - Mid-dosing interval efavirenz plasma concentrations in HIV-1-infected children in
      Rwanda: treatment efficacy, tolerability, adherence, and the influence of CYP2B6
      polymorphisms.
AB  - This study evaluated mid-dosing interval efavirenz plasma concentrations and the
      influence of CYP2B6 polymorphisms in relation to efficacy, tolerability, and
      adherence in 97 Rwandan HIV-infected children (3-16 years). Plasma drug
      concentrations and CYP2B6 polymorphisms were determined. Ten children were
      excluded for nonadherence. Large intersubject variability in efavirenz plasma
      concentrations was found. Of the 87 remaining, efavirenz concentrations were
      therapeutic, supratherapeutic, and subtherapeutic in 67%, 20%, and 14%,
      respectively. No associations were found between efavirenz concentrations and
      central nervous system disturbances or virologic failure. Minor allele
      frequencies were 0.32 (516G>T), 0.33 (785A>G), and 0.09 (983T>C). Polymorphisms
      in CYP2B6 were strongly associated with high efavirenz levels.

PMID- 22481607
TI  - Application of botulinum toxin to clinical therapy:  advances and cautions.
AB  - The therapeutic use of botulinum toxin Type A has followed a novel and
      unanticipated pathway of applications, from its initial application by Scott to
      paralyze the extraocular muscles of the eyes to correct strabismus. In the late
      1970s, Scott formed a company, called Oculinum Inc, to make botulinum toxin Type
      A available for this ophthalmic application. From this modest and limited
      beginning, it has found use for treatment of a plethora of cosmetic,
      neuromuscular, and skeletal disabilities, including cervical dystonia,
      blepharospasm, and temporary improvement in the appearance of moderate to severe
      glabellar lines. Botulinum toxin Type A is now being used as therapy in voiding
      disorders, migraine and tension-type headache, writer's cramp, and laryngeal
      muscle hyperactivity syndromes. It has reduced the spasm and pain associated with
      perianal fissures. It has found application in the reduction of glandular
      function in severe primary axillary hyperhidrosis and sialorrhea. Additional
      applications are being studied in the area of pain management based on its
      apparent ability to inhibit neuropeptide release from nociceptors.

PMID- 22481608
TI  - Optical molecular sensing with semiconductor quantum dots (QDs).
AB  - Semiconductor quantum dots (QDs) exhibit unique optical and photophysical
      properties. These features are implemented to develop optical molecular sensor
      systems. The review addresses the methods to functionalize the QDs with chemical
      capping layers that enable the use of the resulting hybrid structures for
      sensing, and discusses the photophysical mechanisms being applied in the
      different sensor systems. Different methods to design the chemically-modified QDs
      hybrid structures for sensing low-molecular-weight substrates, metal ions, anions
      and gases are presented. These include the functionalization of the QDs with
      ligands that bind ions, the modification of the QDs with substrate-specific
      ligands or receptor units, and the chemical modification of the QDs upon sensing.
      Specific emphasis is directed to describe the cooperative catalytic functions of
      the QDs in the sensing processes, and to address the function of sensing with
      logic-gate operations.

PMID- 22481609
TI  - Defining disability: metaphysical not political.
AB  - Recent discussions surrounding the conceptualising of disability has resulted in
      a stalemate between British sociologists and philosophers. The stagnation of
      theorizing that has occurred threatens not only academic pursuits and the
      advancement of theoretical interpretations within the Disability Studies
      community, but also how we educate and advocate politically, legally, and
      socially. More pointedly, many activists and theorists in the UK appear to
      believe the British social model is the only effective means of understanding and
      advocating on behalf of people with disabilities. This model, largely reliant
      upon materialist research traditions, contends that disability is a form of
      social oppression and hence, is a phenomenon that should be conceptualised in
      social terms. Individual properties such as impairments are disregarded as they
      are viewed to be unimportant in the analysis of the social causes of disability.
      Concurrently, many bioethicists and philosophers have embraced what Tom
      Shakespeare has classified as an 'Interactional Approach' to disability--that
      "the experience of a disabled person results from the relationship between
      factors intrinsic to the individual, and the extrinsic factors arising from the
      wider context in which she finds herself". I intend to demonstrate that the
      benefits of the British social model are now outweighed by its burdens. I
      suggest, as Jerome Bickenbach has, that while it may be somewhat churlish to
      critique the social model in light of its political success, taken literally, it
      implies that people with disabilities require no additional health resources by
      virtue of their impairments. Despite the eloquent arguments that have preceded me
      by interactional theorists, none have been accepted as evidence of fallacious
      reasoning by British social model theorists. This article is an attempt to
      clarify why it is that the types of arguments British social model theorists have
      been offering are misguided. I suggest that the British social model, unlike an
      interactional approach, is unable to provide a realistic account of the
      experience of disability, and subsequently, unable to be properly utilized to
      ensure justice for people with disabilities.

PMID- 22481610
TI  - Unique photocatalytic oxidation reactivity and selectivity of TiO2-graphene
      nanocomposites.
AB  - Mesoporous TiO(2)-graphene nanocomposites are fabricated in high yield via two
      successive steps: (1) hydrothermal hydrolysis of Ti(SO(4))(2) in an acidic
      suspension of graphene oxide to gain TiO(2)-graphene oxide nanocomposites; (2) UV
      assisted photocatalytic reduction of graphene oxide to get the TiO(2)-graphene
      nanocomposites. The anatase TiO(2) nanocrystals with a crystallite size of 10-20
      nm are densely packed and supported on meshy graphene sheets with close
      interfacial contacts, which is confirmed by transmission electron microscopy
      (TEM) together with Raman spectroscopy and X-ray photoelectron spectroscopy
      (XPS). Although a low graphene loading (0-2 wt%) slightly influences the textural
      properties (including the crystallite size, specific surface areas, and pore
      volume etc.), the incorporation of graphene in TiO(2)-graphene nanocomposites
      greatly increases the adsorption capacity towards azo dyes such as MO and MB,
      which is possibly associated with their unique surface properties. Significantly,
      the incorporated graphene exerts combined effects on the adsorption and charge
      transfer dynamics in TiO(2)-graphene nanocomposites, which together endow them
      with good photocatalytic reactivity and tunable photocatalytic selectivity in
      decomposing MO and MB in aqueous solution.

PMID- 22481611
TI  - Methanol, ethanol and hydrogen sensing using metal oxide and metal (TiO(2)-Pt)
      composite nanoclusters on GaN nanowires: a new route towards tailoring the
      selectivity of nanowire/nanocluster chemical sensors.
AB  - We demonstrate a new method for tailoring the selectivity of chemical sensors
      using semiconductor nanowires (NWs) decorated with metal and metal oxide
      multicomponent nanoclusters (NCs). Here we present the change of selectivity of
      titanium dioxide (TiO(2)) nanocluster-coated gallium nitride (GaN) nanowire
      sensor devices on the addition of platinum (Pt) nanoclusters. The hybrid sensor
      devices were developed by fabricating two-terminal devices using individual GaN
      NWs followed by the deposition of TiO(2) and/or Pt nanoclusters (NCs) using the
      sputtering technique. This paper present the sensing characteristics of
      GaN/(TiO(2)-Pt) nanowire-nanocluster (NWNC) hybrids and GaN/(Pt) NWNC hybrids,
      and compare their selectivity with that of the previously reported GaN/TiO(2)
      sensors. The GaN/TiO(2) NWNC hybrids showed remarkable selectivity to benzene and
      related aromatic compounds, with no measurable response for other analytes.
      Addition of Pt NCs to GaN/TiO(2) sensors dramatically altered their sensing
      behavior, making them sensitive only to methanol, ethanol and hydrogen, but not
      to any other chemicals we tested. The GaN/(TiO(2)-Pt) hybrids were able to detect
      ethanol and methanol concentrations as low as 100 nmol mol(-1) (ppb) in air in
      approximately 100 s, and hydrogen concentrations from 1 umol mol(-1) (ppm) to 1%
      in nitrogen in less than 60 s. However, GaN/Pt NWNC hybrids showed limited
      sensitivity only towards hydrogen and not towards any alcohols. All these hybrid
      sensors worked at room temperature and are photomodulated, i.e. they responded to
      analytes only in the presence of ultraviolet (UV) light. We propose a qualitative
      explanation based on the heat of adsorption, ionization energy and solvent
      polarity to explain the observed selectivity of the different hybrids. These
      results are significant from the standpoint of applications requiring room
      temperature hydrogen sensing and sensitive alcohol monitoring. These results
      demonstrate the tremendous potential for tailoring the selectivity of the hybrid
      nanosensors for a multitude of environmental and industrial sensing applications.

PMID- 22481612
TI  - The kinetic role of carboxylate residues in the proximity of the trinuclear
      centre in the O2 reactivity of CotA-laccase.
AB  - Multicopper oxidases catalyze the four-electron reduction of dioxygen to water
      without the release of any reactive oxygen intermediate species. The role of
      carboxylate residue Asp116 located at the exit channel for water molecules of
      CotA-laccase has been investigated by site-saturation mutagenesis. A total of 300
      clones was picked and screened for activity. Five variant enzymes, D116E, D116A,
      D116N, D116T and D116L, were selected for further characterisation. Spectroscopic
      analysis revealed only small perturbations in the geometry of the catalytic Cu
      sites of variants. However, a severe drop in turnover numbers (k(cat)) and
      downshifts by approximately 1-2 units of the optimal pH were observed for the
      oxidation of substrates, as compared with the wild type. The kinetics of
      formation and decay of peroxide intermediate (PI) was studied in type 1 depleted
      (T1D) CotA-laccase and in T1D-D116 or T1D-E498 mutants, previously shown to be
      involved in the mechanism of dioxygen reduction. It is noteworthy that CotA shows
      10 times lower rates of PI formation and 10(3) higher PI decay rates as compared
      with other studied multicopper oxidases. The generation of PI is pH independent
      and mostly unaffected by the D116 or E498 mutations. In contrast, the decay of PI
      is markedly compromised by the replacement of D116 or E498 with non-carboxylate
      residues. The E498 residue appears to be the main protonable species for
      acceleration of PI decay at low pH. The D116 residue seems to be essential in the
      modulation of E498 protonation and in assisting protons to hydroxyl groups bound
      to the T2 Cu.

PMID- 22481613
TI  - It is safe to carry out an MRI scan on patients with SARS providing that is
      conducted in a 1.5 tesla system.

PMID- 22481614
TI  - Marc Maury, 1922-2011: an extraordinary person.

PMID- 22481615
TI  - Visual images for skin cancer prevention: a systematic review of qualitative
      studies.
AB  - Visual images play an important role in educating the public about skin cancer
      prevention. The objectives of this systematic review were to: 1) determine how
      visual images are evaluated in skin cancer and tanning qualitative research
      studies (including theoretical and methodological approaches) and 2) summarize
      and discuss the image-related findings of the studies with respect to cancer
      education and public health. Seven databases were searched (PubMed-MEDLINE,
      EMBASE, PsycINFO, Sociological Abstracts, Social Sciences Full Text, ERIC, and
      ABI/INFORM) using multiple search terms, including MeSH terms, resulting in 5330
      citations. Studies were included if they were in English, peer-reviewed,
      qualitative in design or methodology, dealt with skin cancer or UV exposure, used
      visual images, and had a focus on the public or patients (i.e., not medical
      professionals). Eight studies met the inclusion criteria: seven content analyses
      and one focus group study. Content analysis studies in this review suggest the
      mass media portray Caucasian men and women as unprotected from the sun and with
      tanned skin, and thus, may inform behaviors related to skin cancer risk. The
      focus group study suggests visible minorities may benefit from the incorporation
      of images of melanoma on ethnic skin in cancer education materials. None of the
      studies used visual communication theory to explicitly guide the research, nor
      were standardized tools used for image assessment. The lack of guiding theory and
      standardized assessment instruments can introduce bias in how images are selected
      and used in research on skin cancer education.

PMID- 22481616
TI  - To speak, or not to speak -- do clinicians speak about dying and death with
      geriatric patients at the end of life?
AB  - QUESTIONS UNDER STUDY: Research describing healthcare professionals'
      conversations about issues of dying and death with chronically ill geriatric
      patients is rare, especially in Europe. The study reviews the willingness and
      difficulties of physicians and nurses to speak about dying and death with
      geriatric patients. METHOD: Interview study with 14 physicians and 17 nurses.
      RESULTS: The majority (21/31) of the interviewed physicians and nurses reported a
      considerable willingness to speak about dying and death with patients approaching
      the end of life. Obstacles to addressing this topic included external
      circumstances such as lack of time and/or privacy (14/31); personal reasons, such
      as feeling confronted with one's own mortality (12/31); resistance or denial in
      their patients (12/31); and the cognitive state of the patients (7/31).
      CONCLUSIONS: Discussing and preparing (the patient) for an end-of-life decision
      early enough is a prerequisite of good palliative care. It is an ethical
      obligation on the side of the healthcare professionals to support openness,
      respect for autonomy, and dignity by addressing issues of dying and death with
      the patient in order to help facilitate advance care planning.

PMID- 22481618
TI  - The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human
      hepatocellular carcinoma cells.
AB  - PURPOSE: Rho kinase is an important factor in tumor progression. We demonstrated
      that Rho kinase-associated coil-containing protein kinase (ROCK) is expressed in
      hepatic tissues in hepatocellular carcinoma (HCC) and confirmed its roles in cell
      survival in HCC cells using the ROCK inhibitor, fasudil. METHODS: ROCK protein
      levels were estimated in hepatic tissues with HCC compared with healthy liver
      tissues or hepatic hemangioma tissues using immunohistochemistry. Furthermore,
      HepG2 and Huh7 cells were cultured with ROCK inhibitor, fasudil for 24 h in
      vitro. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5
      (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, and
      apoptotic cells were detected by cell death ELISA. The expression apoptosis
      related proteins were analyzed using Western blotting. RESULTS: Fasudil
      significantly decreased cell proliferation and induced apoptosis mediated by
      increases in p53, Bax, caspase-9, and caspase-3 in HepG2 and Huh7 cells. The
      induction of apoptosis was inhibited in HCC cells precultured with p53 decoy
      oligodeoxynucleotide. CONCLUSION: These results suggest that ROCK inhibits the
      p53-mediated apoptosis pathway in HCC. Fasudil may thus be a beneficial approach
      to HCC therapy.

PMID- 22481617
TI  - Cholesteatoma-associated fibroblasts modulate epithelial growth and
      differentiation through KGF/FGF7 secretion.
AB  - The keratinocyte growth factor (KGF/FGF7), produced by stromal cells, is a key
      paracrine mediator of epithelial proliferation, differentiation and migration.
      Expression of the growth factor is increased in wound healing and in
      hyperproliferative epithelial diseases, as a consequence of the activation of
      dermal fibroblasts by the inflammatory microenvironment. The middle ear
      cholesteatoma, an aural epidermal pathology characterized by keratinocyte
      hyperproliferation and chronic inflammation, may represent a model condition to
      study the epithelial-mesenchymal interactions. To develop an in vitro model for
      this disease, we isolated and characterized human primary cultures of fibroblasts
      associated with the cholesteatoma lesion, analyzing their secretory behaviour and
      degree of differentiation or activation. Compared to the perilesional or control
      normal fibroblasts, all cultures derived from cholesteatoma tissues were less
      proliferating and more differentiated and their highly variable activated
      phenotype correlated with the secretion of KGF as well as of metalloproteases 2
      and 9. Culture supernatants collected from the cholesteatoma-associated
      fibroblasts were able to increase the proliferation and differentiation of human
      keratinocytes assessed by the expression of Ki67 and keratin-1 markers. The
      single crucial contribution of the KGF released by fibroblasts on the
      keratinocyte biological response was shown by the specific, although partial,
      block induced by inhibiting the KGF receptor or by immunoneutralizing the growth
      factor. Altogether, these results suggest that the activation of the stromal
      fibroblasts present in the pathological tissue, and the consequent increased
      secretion of KGF, play a crucial role in the deregulation of the epidermal
      proliferation and differentiation.

PMID- 22481619
TI  - [Short-course treatment of vulvovaginal candidiasis: comparative study of
      fluconazole and intra-vaginal fenticonazole].
AB  - AIM: The aim of this paper was to compare the efficacy of fluconazole 150 mg and
      intra-vaginal fenticonazole 600mg in short-course treatment of the acute episode
      of vulvovaginal candidiasis (VVC). METHODS: In a prospective study, 80 patients
      with clinical and mycological (SavvyCheckTM test) confirmed VVC were enrolled and
      divided randomly in two groups. Forty patients received oral fluconazole (150
      mg), whereas 40 patients received intra-vaginal tablet fenticonazole (600 mg).
      Two sequential doses of azole agents were given 3 days apart (short-course
      treatment). Second and third visits were done for all patients seven and 30+/-5
      days after treatment. RESULTS: At the second visit, 31 patients (77.5%) were
      cured clinically (Sobel score <4) in fluconazole group and 32 patients (80%) in
      fenticonazole group (P=0.876). The vulvovaginal pruritus was reduced in lower
      time in fenticonazole patients than in fluconazole group (mean 2.3 days versus
      4.5 days, P=0.047). At the third visit, three patients in fluconazole group and
      two patients in fenticonazole group had clinical sign of VVC. CONCLUSION:
      Fluconazole and intravaginal fenticonazole are both effective to cure symptoms of
      VVC but fenticonazole appears to reduce the pruritus in less time.

PMID- 22481620
TI  - Chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer:
      has this regimen still a role as neoadjuvant setting?
AB  - AIM: Neoadjuvant chemotherapy represents a promising alternative to concomitant
      chemo-radiation therapy in locally advanced cervical cancer patients. The aim of
      this study was the evaluation of pathologic response rates, toxicity and
      predictors of response in locally advanced cervical cancer patients treated with
      neoadjuvant cisplatin and paclitaxel followed by radical surgery. METHODS:
      Fourteen patients with stage IB2 to IIB cervical cancer received three cycles of
      cisplatin 75 mg/m2 and paclitaxel 175 mg/m2 intravenously every three weeks
      followed by radical hysterectomy and bilateral pelvic lymphadenectomy. Toxicity,
      pathologic response and predictors of response were evaluated. RESULTS:
      Chemotherapy related toxicities we-re as follows: alopecia 100%, asthenia 35.7%;
      nausea and vomiting 14.3%; paclitaxel hypersensitivity 7.1%, neutropenia 7.1%.
      Optimal, partial and no pathologic response was achieved in 21.4%, 64.3% and
      14.2% of the patients, respectively. Based on lack of pathologic risk factors,
      43% of the patients did not receive any adjuvant radiotherapy. Better response
      rates were obtained in patients with stage IIB, tumor diameter <5 cm, Hb >12 g/dL
      and SCC antigen <1.5 mg/dL. None of these variables reached statistical
      significance. CONCLUSION: Neoadjuvant chemotherapy with cisplatin and paclitaxel
      in locally advanced cervical cancer appeared to be well-tolerated. Even though
      the TIP regimen has been shown to be more effective than the TP regimen in
      randomized controlled prospective trial, the TP regimen remains a reasonable
      alternative in those patients in whom the TIP regimen is considered or shown to
      be too toxic.

PMID- 22481621
TI  - Neonatal outcomes of late preterm deliveries with pre-eclampsia.
AB  - AIM: The aim of the study was to examine the impact of pre-eclampsia on neonatal
      outcomes of late preterm deliveries. METHODS: A retrospective study was
      conducted, enrolling pregnancies delivered between 34 0/7 and 36 6/7 weeks of
      gestation during the period 2004-2007 in a large tertiary center. Pregnancies
      were divided in group 1, including those complicated with pre-eclampsia and group
      2, including normotensive cases. Epidemiological characteristics, mode of
      delivery and complications contributing in late preterm delivery were initially
      studied. Neonatal morbidity parameters of our interest included mean Apgar score
      in the 1st and 5th minute, admission to Neonatal Intensive Care Unit (NICU) and
      need for emergency intubation. Intrauterine growth retardation (IUGR), low birth
      weight (LBW) and very LBW (VLBW), respiratory distress syndrome (RDS),
      hypoglycemia, NICU infection, abnormal cerebral ultrasonographic findings and
      duration of NICU residence were also compared between the two groups. RESULTS:
      Out of 363 late preterm pregnancies, 29 (8%) were delivered because of pre
      eclampsia. Mean gestational week and birth weight were significantly lower in
      group 1. The rate of elective caesarean section was also significantly higher in
      this group. The same observation was made concerning rates of IUGR, LBW and VLBW
      neonates. Furthermore, incidence of NICU admission and hypoglycemia were
      significantly higher in the group of infants born by pre-eclamptic mothers.
      Incidence of RDS and cerebral echo pathology were also higher, but without
      significant difference when compared to group 2. CONCLUSION: Neonatal adverse
      outcomes were increased in late preterm infants of pre-eclamptic women in
      comparison with those of normotensive women.

PMID- 22481622
TI  - [Maternal body mass index and breast feeding].
AB  - AIM: The aim of this paper was to determine whether maternal BMI influences
      breast-feeding practice in quality and duration METHODS: A retrospective case
      control study were included Fifty women with Body Max Index (BMI) >=25 kg/m2
      considered overweigh and obese and fifty controls with BMI<25 kg/m2 who delivered
      in our clinic between 2010 and 2011. RESULTS: The incidence of breast-feeding was
      significantly lower in overweight and obese women compared with normal weight.
      Breastfeeding length was negatively related to prepregnancy BMI but not to
      gestational weight gain, method of delivery or lactation integration. Obese women
      presented an elevated Body Max Index one year apart from childbirth and are
      correlated to maternal complications during breastfeeding. CONCLUSION: Maternal
      overweight and obesity is negatively correlated to duration and quality of
      lactation.

PMID- 22481623
TI  - Colposcopy and management of microinvasive squamous cell carcinoma.
AB  - In the last decades both the relative proportion and absolute incidence of micro
      invasive cervical cancer (MIC) have ten times increased in developed Countries
      mainly in young women aged less than 40 years. Despite the controversial views
      expressed about the selection criteria, there has been an increasing recent trend
      to treat MIC patients with a conservative, less radical, fertility-sparing
      approach. Several histologic tumor-related features have to be considered in
      planning conservative treatment: depth of infiltration (DI), lymph-vascular
      involvement (LVSI) width of the lesion and the number of quadrants involved at
      colposcopy are the most important factors in predicting disease persistence or
      recurrence in multivariate survival analysis. Furthermore MIC can be considered
      safely treated only when surgical limits of the cone are completely in sano,
      since there is a high chance that residual disease remains behind. Moreover a
      close long-term surveillance should be scheduled for the MIC patients
      conservatively treated and, in the absence of specific guidelines, 10 years
      should be the current accepted follow up for stage IA disease.

PMID- 22481624
TI  - Management of the abnormal Papanicolaou smear and colposcopy in pregnancy: an
      evidenced-based review.
AB  - Women diagnosed with abnormal Papanicolau smears or cervical abnormalities during
      pregnancy present a challenge to health care providers, as conventional
      management guidelines appropriate for the non-pregnant population may be
      contraindicated. The physiologic effects of pregnancy that may result in greater
      difficulty with the colposcopic examination include increased cervical mucus
      production that may obscure visualization, cervical hyperemia, gland prominence,
      and eversion of the columnar epithelium. The squamo-columnar junction may also be
      difficult to visualize in early pregnancy, but will often evert as the pregnancy
      continues. Because of these changes, cervical dysplasia may have a more prominent
      appearance in the gravid patient. Therefore, colposcopy should be performed by a
      skilled examiner with expertise in the cervical changes of pregnancy. The primary
      goal of colposcopy during pregnancy is to exclude the presence of invasive
      cancer, and thus, many cervical lesions may be followed with serial cytology and
      colposcopy during pregnancy or by deferring further colposcopic examination until
      the postpartum period. Cervical biopsy should be avoided unless a malignancy is
      suspected and endocervical sampling is contraindicated. Herein, we present a
      contemporary, evidence-based review of the colposcopic examination and guidelines
      for triaging and evaluating abnormal cervical cytology and lesions that are
      diagnosed during pregnancy.

PMID- 22481625
TI  - Efficacy, safety, acceptability and affordability of cryotherapy: a review of
      current literature.
AB  - As a result of widespread screening and treatment programs, the incidence of
      cervical cancer has decreased by as much as 75% in the developed world. Commonly
      used treatment modalities for precancerous lesions include cone biopsy, the Loop
      Electrosurgical Excision Procedure (LEEP), laser ablation and cryotherapy. In
      recent years LEEP has replaced cryotherapy as a commonly provided outpatient
      procedure in many places; however increased awareness of the burden of cervical
      cancer in the developing world and increased awareness of long term consequences
      of LEEP - such as cervical insufficiency - have renewed interest in cryotherapy.
      We reviewed current literature addressing the technique, efficacy, safety and
      acceptability of cryotherapy, as well as special topics such as cost
      effectiveness, HIV, and low resource settings. Among studies we reviewed, cure
      rates ranged from 56.8-96.6% among prospective controlled trials and from 70
      95.5% among observational studies. Cryotherapy has very low complication rates
      and serious complications requiring medical intervention or affecting future
      reproductive outcomes are extremely rare. Side effects including vaginal
      discharge and cramping are temporary, generally self-limited, and well tolerated
      after anticipatory patient counseling. When surveyed, women find cryotherapy
      highly acceptable. Compared to other treatment modalities, cryotherapy is very
      affordable and feasible to integrate into cervical cancer screening and treatment
      programs.

PMID- 22481626
TI  - Colposcopy.
AB  - Though in the 1980s, colposcopically-directed biopsy excluded over 90% of CIN 3
      and cancer (CIN 3+), recent reviews found sensitivity of colposcopically-directed
      biopsy for CIN 3+ of 50-65%. Studies from China showed that the sensitivity of
      colposcopically-directed biopsy for CIN 3+ is higher for large CIN 3+ than for
      small CIN 3+ and higher for associated high-grade cervical cytology than for low
      grade cervical cytology. Colposcopically-directed biopsy excluded over 90% of CIN
      3+ in the 1980s because colposcopy clinics in the 1980s evaluated women with high
      grade cytology that had large CIN 3+; it no longer excludes CIN 3+ well because
      current colposcopy clinics evaluate women with low-grade cytology that have small
      CIN 3+. When colposcopically-directed biopsy is used to exclude CIN 3+ our
      understanding of the natural history of CIN is skewed, errors occur in defining
      appropriate screening practice, and inaccurate diagnosis results in incorrect
      treatment. The impression that CIN is more common on the anterior lip of the
      cervix is an artifact introduced by the inaccuracy of colposcopy. An unjustified
      enthusiasm for screening with acetic acid aided visual inspection (VIA) occurred
      when the sensitivity of VIA for CIN 3+ was inflated by screening studies using
      colposcopically-directed biopsy as the gold-standard for CIN 3+. To limit the
      harm of inaccurate diagnosis associated with colposcopically-directed biopsy, at
      colposcopy we advise random biopsies at the squamocolumnar junction in cervical
      quadrants without visible lesions and, unless the woman is pregnant, endocervical
      curettage (ECC). As the diagnosis of CIN 3+ solely by ECC is uncommon in women
      under age 25, the ECC may be omitted in women under age 25 years. If multiple
      cervical biopsies are performed, to limit discomfort, a bronchoscopy biopsy
      instrument which obtains 2-mm biopsies should be used.

PMID- 22481627
TI  - Extracellular K+ and astrocyte signaling via connexin and pannexin channels.
AB  - Astrocytes utilize two major pathways to achieve long distance intercellular
      communication. One pathway involves direct gap junction mediated signal
      transmission and the other consists of release of ATP through pannexin channels
      and excitation of purinergic receptors on nearby cells. Elevated extracellular
      potassium to levels occurring around hyperactive neurons affects both gap
      junction and pannexin1 channels. The action on Cx43 gap junctions is to increase
      intercellular coupling for a period that long outlasts the stimulus. This long
      term increase in coupling, termed "LINC", is mediated through calcium and
      calmodulin dependent activation of calmodulin dependent kinase (CaMK). Pannexin1
      can be activated by elevations in extracellular potassium through a mechanism
      that is quite different. In this case, potassium shifts activation potentials to
      more physiological range, thereby allowing channel opening at resting or slightly
      depolarized potentials. Enhanced activity of both these channel types by
      elevations in extracellular potassium of the magnitude occurring during periods
      of high neuronal activity likely has profound effects on intercellular signaling
      among astrocytes in the nervous system.

PMID- 22481628
TI  - Charge shielding effects on gene delivery of polyethylenimine/DNA complexes:
      PEGylation and phospholipid coating.
AB  - Polyethylenimine (PEI) is an efficient cationic polymer for gene delivery, but
      defective in biocompatibility. In this study, we developed two different
      strategies to shield the positively charged PEI/DNA complexes: PEGylation and
      lipid coating. The physicochemical properties, cytotoxicity and transfection
      efficiency of the two gene delivery systems were investigated. Both PEGylation
      and lipid coating succeeded in reducing the zeta-potential of the complexes.
      Lipid-coated PEI/DNA complexes (LPD complexes) and PEI/DNA complexes exhibited
      similar cytotoxicity, whereas PEG-PEI/DNA complexes showed lower cytotoxicity,
      especially at high N/P ratios. LPD complexes were less efficient in transfection
      compared to PEG-PEI/DNA complexes. The transfection efficiency was influenced
      remarkably by cytotoxicity and surface charge of the complexes. Intracellular
      processes studies revealed that endosomal release might be one of the rate
      limiting steps in cell transfection with PEI as a gene delivery carrier.

PMID- 22481629
TI  - [Whiplash injury as a function of the accident mechanism. Neuro-otological
      differential diagnostic findings].
AB  - BACKGROUND: Depending on the type of collision, car occupants who are involved in
      traffic accidents are often exposed to the unexpected effects on the cervical
      spine of traumatic stimuli from different directions. In a rear-end collision or
      a frontal collision of the car it is most likely that there is an effect of
      linear acceleration and a lateral or side impact acceleration of axial rotation
      on the cervical spine. The neuro-otological manifestations of whiplash injuries
      that can occur in response to various trauma mechanisms have not yet been
      sufficiently investigated. METHOD: Data from 64 patients who suffered a whiplash
      injury were selected for analysis. In 32 patients the trauma mechanism was a
      sudden action on the cervical spine from a linear impulse caused by a head-on
      collision of cars or rear-end collision. In the other 32 patients the trauma
      mechanism was a sudden action of an axial neck rotation at a side impact
      collision or a cross collision. The study compared the results of neuro
      otological findings between the two patient groups. RESULTS: A comparison of the
      neuro-otological examination data of 64 patients revealed that there were 32
      patients who had a sudden injury mechanism of cervical axial rotation, the
      prevalence of central vestibular and sensory impairments, such as pathological
      central nystagmus disinhibition, pathological changes in the auditory brainstem
      evoked potentials (ABEP), the auditory evoked cortical potentials (ALEP) and
      visual evoked potentials (VEP). In the second group of patients where the injury
      mechanism consisted of an unexpected linear momentum, peripheral vestibular and
      sensory disorders were predominant. CONCLUSION: The observed differences in neuro
      otological manifestations of whiplash trauma, which occur depending on the trauma
      mechanism, can be used for differential diagnostic purposes. The whiplash
      injuries of the cervical spine induced by an axial rotation acceleration showed a
      prevalence of central vestibular and sensory disturbances, while the whiplash
      injuries of the cervical spine induced by a linear acceleration showed a
      prevalence of peripheral vestibular, sensory and vestibulospinal disorders. Our
      data thus show in the first group of patients a prevalence of retrocochlear,
      supratentorial and subcortical lesions of the auditory tract, and brain lesions
      of the optic tract in the occipital pole and in the visual cortex.

PMID- 22481630
TI  - Prebiotic-like chemistry on Titan.
AB  - Titan, the largest satellite of Saturn, is the only one in the solar system with
      a dense atmosphere. Mainly composed of dinitrogen with several % of methane, this
      atmosphere experiences complex organic processes, both in the gas and aerosol
      phases, which are of prebiotic interest and within an environment of
      astrobiological interest. This tutorial review presents the different approaches
      which can be followed to study such an exotic place and its chemistry:
      observation, theoretical modeling and experimental simulation. It describes the
      Cassini-Huygens mission, as an example of observational tools, and gives the new
      astrobiologically oriented vision of Titan which is now available by coupling the
      three approaches. This includes the many analogies between Titan and the Earth,
      in spite of the much lower temperature in the Saturn system, the complex organic
      chemistry in the atmosphere, from the gas to the aerosol phases, but also the
      potential organic chemistry on Titan's surface, and in its possible internal
      water ocean.

PMID- 22481631
TI  - Solution structure of Fe(II)-azide-bleomycin derived from NMR data: transition
      from Fe(II)-bleomycin to Fe(II)-azide-bleomycin as derived from NMR data and
      structural calculations.
AB  - The coordination cage of the metal center in Fe(II)-bleomycin has been proposed
      to consist of the secondary amines in beta-aminoalanine, the
      pyrimidinylpropionamide and imidazole rings, and the amide nitrogen in beta
      hydroxyhistidine as equatorial ligands, and the primary amine in beta
      aminoalanine and either the carbamoyl group in mannose or a solvent molecule
      occupying the axial sites. With the aim of supporting or not supporting
      coordination of a water molecule to the metal center in Fe(II)-bleomycin, the
      solution structure of Fe(II)-azide-bleomycin has been derived from NMR data. The
      structural changes that occur in Fe(II)-bleomycin upon azide binding have been
      monitored by comparing the experimental results with those obtained from the
      calculated structures for both bleomycin adducts. The results of this
      investigation strongly support a model of Fe(II)-bleomycin with six endogenous
      ligands as the most likely structure held in solution by this metallobleomycin in
      the absence of DNA.

PMID- 22481633
TI  - Acromegalic gigantism, physicians and body snatching. Past or present?
AB  - The skeletons of 2 famous acromegalic giants: Charles Byrne (1761-1783) and Henri
      Cot = Joseph Dusorc (1883-1912) and the embalmed body of the famous acromegalic
      giant Edouard Beaupre (1881-1904) all ended up in the medical collections of
      museums despite the fact that these patients had never donated or even refused to
      donate their corpses, nor had their relatives given permission. The corpse of the
      acromegalic giant John Aasen (1890-1938) was voluntarily donated to a physician
      annex collector of trivia from acromegalic giants. The autopsy on the acromegalic
      giant John Turner (1874-1911) was performed during his funeral ceremony without
      the relatives being informed. Only recently, the acromegalic giant Alexander
      Sizonenko (1959-2012) was made a financial offer during his life in exchange for
      his body after his death. The case-histories of these 6 patients and also the
      circumstances that led to the (in-) voluntary donation of their bodies are
      reviewed.

PMID- 22481632
TI  - Changes in acromegaly treatment over four decades in Spain: analysis of the
      Spanish Acromegaly Registry (REA).
AB  - Since 1997 there is an online National Registry of acromegalic patients in Spain
      (REA). We aimed to study changes in acromegaly treatment and outcomes over the
      last four decades in Spain. In REA clinical and biochemical data are collected at
      diagnosis and updated every one to 2 years. We analyzed the first treatment
      received and the different treatments administered according to decade of
      diagnosis of acromegaly: prior to 1980, 1980-1989, 1990-1999 and 2000-2009.
      Surgical cure rates according to pretreatment with long-acting somatostatin
      receptor ligands (SRLs) were also analyzed. 1,658 patients were included of which
      698 had accurate follow-up data. Treatment of acromegaly changed over time.
      Surgery was the main treatment option (83.8 %) and medical treatment was widely
      used (74.7 %) both maintained over decades, while radiation therapy declined
      (62.8, 61.6, 42.2 and 11.9 % over decades, p < 0.001). First treatment type also
      changed: surgery was the first line option up until the last decade in which
      medical treatment was preferred (p < 0.001). Radiotherapy was barely used as
      first treatment. Treatment combinations changed over time (p < 0.001). The most
      common treatment combination (surgery plus medical therapy), was received by
      24.4, 16.4, 25.3 and 56.5 % of patients over decades. Medical treatment alone was
      performed in 7.3, 6, 7.2 and 14.7 % over decades. Type of medical treatment also
      changed, SRLs becoming the first medical treatment modality in the last decades,
      whereas dopamine agonist use declined (p < 0.001). Surgical cure rates improved
      over decades (21, 21, 36 and 38 %, p = 0.002) and were not influenced by SRL pre
      surgical use. Acromegaly treatment has changed in Spain in the last four decades.
      Surgery has been the main treatment option for decades; however, medical therapy
      has replaced surgery as first line in the last decade and radiotherapy rates have
      clearly declined. SRLs are the most used medical treatment.

PMID- 22481634
TI  - Comparative phylogenies of ribosomal proteins and the 16S rRNA gene at higher
      ranks of the class Actinobacteria.
AB  - The 16S rRNA-based hierarchical system is considered to be the backbone of
      prokaryote taxonomy at the genus level and above. However, in the class
      Actinobacteria, the topology of the 16S rRNA-based tree is highly unsteady, and
      relationships between several families and orders are ambiguous. Recently,
      phylogenomic information was claimed to provide a more comprehensive
      understanding of prokaryotic systematics in the genomics era. In this article, a
      comparative phylogenetic analysis of the class Actinobacteria was carried out
      using 16S rRNA gene sequences and a set of 46 ribosomal proteins (RPs).
      Phylogenies based on concatenated RP sequences were generally congruent with 16S
      rRNA phylogenies, but higher bootstrap values supported the branching orders in
      the former trees. RP-based trees constructed by the maximum-likelihood and
      neighbor-joining algorithms provided better-defined phylogenetic relationships
      within the Actinobacteria and clarified the relationships and positions of
      several orders, such as Micrococcales and Frankiales. The RP-based phylogeny
      approach may thus provide a sound basis for assessing the Actinobacteria.

PMID- 22481635
TI  - [Additional classification "medicinal tumor therapy": statement by the German
      Society of Residents in Urology (GeSRU)].

PMID- 22481636
TI  - Impact of adherence to the GOLD guidelines on symptom prevalence, lung function
      decline and exacerbation rate in the Swiss COPD cohort.
AB  - PRINCIPLES: The Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      guidelines aim to optimise chronic obstructive pulmonary disease (COPD) diagnosis
      and treatment.  However, little is known about the extent to which general
      practitioners' (GP) adherence to GOLD guidelines improves patient outcomes.
      METHODS: In this questionnaire-based study, COPD patients were screened and
      enrolled; exacerbation history was recorded, and demographic, spirometric and
      management data were collected for 12 months. Spirometry was performed at least
      every 6 months according to American Thoracic Society guidelines. Based on these
      data, patients were grouped into GOLD COPD severity classifications. Data were
      expressed as the difference between baseline and month 12. RESULTS: Among 139
      GPs, 454 patients were analysed regarding baseline and 12 month data. There was
      no significant change in distribution of GOLD COPD severity grades, lung function
      or guideline adherence. Chronic cough and sputum production were significantly
      reduced (p <0.001; p <0.020), as was exacerbation rate (p = 0.041). Factors
      associated with exacerbations were male sex, asthma and cerebrovascular insult as
      a co-morbidity. Exacerbation rate was significantly reduced in patients treated
      with combination therapy (long-acting beta2-agonist (LABA)+ inhaled
      corticosteroids (ICS); p = 0.0178) and long-acting anticholinergics (LAAC; p =
      0.0011). Patients treated per guidelines had no advantage in lung function,
      estimation of symptom prevalence or, most importantly, exacerbation rate.
      CONCLUSIONS: While there was no improvement in adherence to GOLD guidelines,
      disease severity was not affected detrimentally, suggesting that guideline
      adherence does not seem to impact symptom prevalence, exacerbation rate or lung
      function decline after one year of follow up.

PMID- 22481637
TI  - Hydration assessment using the cardiovascular response to standing.
AB  - The cardiovascular response to standing (sit-to-stand change in heart rate;
      SSDeltaHR) is commonly employed as a screening tool to detect hypohydration (body
      water deficit). No study has systematically evaluated SSDeltaHR cut points using
      different magnitudes or different types of controlled hypohydration. The
      objective of this study was to determine the diagnostic accuracy of the often
      proposed 20 b/min SSDeltaHR cut point using both hypertonic and isotonic models
      of hypohydration. Thirteen healthy young adults (8M, 5F) underwent three bouts of
      controlled hypohydration. The first bout used sweating to elicit large losses of
      body water (mass) (>3 % sweat). The second two bouts were matched to elicit 3 %
      body mass losses (3 % diuretic; 3 % sweat). A euhydration control trial (EUH) was
      paired with each hypohydration trial for a total of six trials. Heart rate was
      assessed after 3-min sitting and after 1-min standing during all trials.
      SSDeltaHR was compared among trials, and receiver operator characteristic curve
      analysis was used to determine diagnostic accuracy of the 20 b/min SSDeltaHR cut
      point. Volunteers lost 4.5 +/- 1.1, 3.0 +/- 0.6, and 3.2 +/- 0.6 % body mass
      during >3 % sweat, 3 % diuretic, and 3 % sweat trials, respectively. SSDeltaHR
      (b/min) was 9 +/- 8 (EUH), 20 +/- 12 (>3 % sweat; P < 0.05 vs. EUH), 17 +/- 7 (3
      % diuretic; P < 0.05 vs. EUH), and 13 +/- 11 (3 % sweat). The 20 beats/min cut
      point had high specificity (90 %) but low sensitivity (44 %) and overall
      diagnostic accuracy of 67 %. SSDeltaHR increased significantly in response to
      severe hypertonic hypohydration and moderate isotonic hypohydration, but not
      moderate hypertonic hypohydration. However, the 20 beats/min cut point afforded
      only marginal diagnostic accuracy.

PMID- 22481638
TI  - Cloning, expression and characterization of a halotolerant esterase from a marine
      bacterium Pelagibacterium halotolerans B2T.
AB  - An esterase PE10 (279 aa) from Pelagibacterium halotolerans B2(T) was cloned and
      overexpressed in Escherichia coli Rosetta in a soluble form. The deduced protein
      was 29.91 kDa and the phylogenetic analysis of the deduced amino acids sequence
      showed it represented a new family of lipolytic enzymes. The recombinant protein
      was purified by Ni-NTA affinity chromatography column and the characterization
      showed its optimal temperature and pH were 45  degrees C and pH 7.5,
      respectively. Substrate specificity study showed PE10 preferred short chain p
      nitrophenyl esters and exhibited maximum activity toward p-nitrophenyl acetate.
      In addition, PE10 was a halotolerant esterase as it was still active under 4 M
      NaCl. Three-dimensional modeling of PE10 suggested that the high negative
      electrostatic potential on the surface may relevant to its tolerance to high salt
      environment. With this halotolerance property, PE10 could be a candidate for
      industrial use.

PMID- 22481639
TI  - Characterization of NADP+-specific L-rhamnose dehydrogenase from the
      thermoacidophilic Archaeon Thermoplasma acidophilum.
AB  - Thermoplasma acidophilum utilizes L-rhamnose as a sole carbon source. To
      determine the metabolic pathway of L-rhamnose in Archaea, we identified and
      characterized L-rhamnose dehydrogenase (RhaD) in T. acidophilum. Ta0747P gene,
      which encodes the putative T. acidophilum RhaD (Ta_RhaD) enzyme belonging to the
      short-chain dehydrogenase/reductase family, was expressed in E. coli as an active
      enzyme catalyzing the oxidation of L-rhamnose to L-rhamnono-1,4-lactone. Analysis
      of catalytic properties revealed that Ta_RhaD oxidized L-rhamnose, L-lyxose, and
      L-mannose using only NADP(+) as a cofactor, which is different from
      NAD(+)/NADP(+)-specific bacterial RhaDs and NAD(+)-specific eukaryal RhaDs.
      Ta_RhaD showed the highest activity toward L-rhamnose at 60  degrees C and pH 7.
      The K (m) and k (cat) values were 0.46 mM, 1,341.3 min(-1) for L-rhamnose and 0.1
      mM, 1,027.2 min(-1) for NADP(+), respectively. Phylogenetic analysis indicated
      that branched lineages of archaeal RhaD are quite distinct from those of Bacteria
      and Eukarya. This is the first report on the identification and characterization
      of NADP(+)-specific RhaD.

PMID- 22481640
TI  - Current status and future challenges of deep brain stimulation in Switzerland.
AB  - QUESTIONS UNDER STUDY: Deep brain stimulation (DBS) has become a standard therapy
      for some forms of severe movement disorders and is investigated for other
      neurological and psychiatric disorders, although many scientific, clinical and
      ethical issues are still open. We analyse how the Swiss DBS community addresses
      these problematic issues and future challenges. METHODS: We have performed a
      survey among Swiss DBS centres and a Delphi study with representatives of all
      centres and further stakeholders related to the topic. RESULTS: The current DBS
      infrastructure in Switzerland consists of seven facilities. About 850-1,050
      patients have received a DBS system in Switzerland for various indications since
      its advent in 1976. Critical issues like patient selection and dealing with side
      effects are in accordance with international standards. There are indications of
      a conservative referral practice in Switzerland for DBS interventions, but the
      data available do not allow verifying or refuting this point. CONCLUSIONS: Issues
      to investigate further are whether or not there is an unmet medical need with
      respect to DBS, long-term medical and psychosocial sequelae of the intervention,
      conditions for enhancing the (research) collaboration of Swiss DBS centers, and
      the effect of the recent decision to reduce the number of DBS centres to 4 (resp.
      possibly 3) on the potential of this therapeutic approach.

PMID- 22481641
TI  - Prognostic value of high-sensitivity troponin I versus troponin T in acute
      coronary syndromes.
AB  - BACKGROUND: Despite superior diagnostic accuracy of high-sensitivity cardiac
      troponins, their prognostic value has not been validated against conventional
      cardiac troponins. OBJECTIVE: To test the prognostic value of high-sensitivity
      cardiac troponin I (hs-cTnI), compared with conventional cardiac troponin T
      (cTnT) in the setting of non-ST elevation acute coronary syndromes. METHODS: At
      hospital admission, a plasma sample was collected from 103 consecutive patients
      with unstable angina or non-ST elevation acute myocardial infarction. In this
      sample, troponin was measured both by hs-cTnI and cTnT methods. Their prognostic
      value was compared as to the occurrence of major cardiovascular events, defined
      as a combination of death, nonfatal acute myocardial infarction or refractory
      unstable angina during hospitalization. RESULTS: During median hospitalization of
      8 days (interquartile range = 5 - 11), the incidence of cardiovascular events was
      10% (5 deaths, 3 non-fatal myocardial infarctions and 2 non-fatal refractory
      anginas). High-sensitivity troponin I significantly predicted cardiovascular
      events, with a C-statistics of 0.73 (95% CI = 0.59 - 0.87), similarly to cTnT
      (0.70; 95% CI = 0.55 - 0.84) - P = 0.75. The definition of positive cardiac
      marker that provided the best prognostic accuracy was hs-cTnI > 0.055 ug/L and
      cTnT > 0.010 ug/L, with equal sensitivity of 90% and specificity of 52% for both
      assays. Positive hs-cTnI was associated with 17% incidence of events, compared
      with 2% in patients with negative hs-cTnI (P = 0.02). CONCLUSION: High
      sensitivity troponin I predicts cardiovascular events similarly to conventional
      troponin T in the setting of non-ST-elevation ACS.

PMID- 22481643
TI  - Quality of life of hypertensive patients and comparison of two instruments of
      HRQOL measure.
AB  - BACKGROUND: Measuring health-related quality of life (QOL) helps evaluating the
      efficiency of a treatment and identifies problems with major impact on the
      patient's QOL. However, these measures are safer if assessed by generic and
      specific instruments together, where it is necessary to check for compatibility
      between these and avoid repetitions and contradictions between the domains.
      OBJECTIVE: To describe the quality of life of hypertensive patients and to
      evaluate the compatibility of a specific instrument (MINICHAL) and a generic
      instrument (SF-36). METHODS: One hundred adult hypertensive under outpatient care
      were interviewed. The mean HRQOL as measured by MINICHAL was 6.64 (SD 6.04) in
      mental status and average of 5.03 (SD 4.11) in the state of somatic
      manifestations. The means for the instrument SF-36 were in ranking order:
      limitation due to physical aspects 47.3 (SD 42.9), vitality 57.4 (SD 19.7),
      limitation due to emotional aspects 58 (SD 44.7), functional capacity 58.7 (SD
      27.8), pain 60.4 (SD 26.3), general health condition 60.7 (SD 22.7), mental
      health 66.8 (SD 22.1) and social aspects 78 (SD 26.1). RESULTS: The MINICHAL
      significantly correlated (p <0.001) with the SF-36 in all domains. CONCLUSION:
      The MINICHAL proved to be a useful tool in the assessment of HRQOL in patients
      with hypertension.

PMID- 22481642
TI  - Clinical and echocardiographic parameters associated with low chronotropic index
      in non-elderly patients.
AB  - BACKGROUND: Despite abundant evidence of increased morbidity and mortality,
      chronotropic incompetence (CI) is not a routine diagnosis well defined in
      protocols of cardiac evaluation and its clinical importance is still
      underestimated. OBJECTIVE: To evaluate the clinical and echocardiographic
      parameters associated with HF in non-elderly patients submitted to stress
      echocardiography (SE). METHODS: One thousand seven hundred ninety-eight patients
      with a mean age of 48.4 +/- 7.5 years, who underwent SE between January/2000 and
      August/2009 were evaluated. Patients with chronotropic index smaller than 0.8
      were considered chronotropic incompetent as compared to competent patients as to
      clinical and echocardiographic characteristics. RESULTS: The duration of the
      exercise was 9.3 +/- 2.4 minutes on average. Two hundred and seventy (15%)
      patients were chronotropic incompetent. The chronotropic index of this group was
      0.7 +/- 0.1 vs. 1.0 +/- 0.1 for competent patients. Multivariate logistic
      regression analysis identified the following parameters as independently
      associated with HF: dyspnea on examination [odds ratio (OR) = 4.27, p <0.0001],
      previous chest pain on medical history (OR = 1.51; p = 0.0111), higher left
      ventricular mass rate in incompetent patients (LVMI) (OR = 1.16, p = 0.0001),
      metabolic equivalents (METs) (OR = 0.70, p = 0 , 0001), ST segment depression (OR
      = 0.58, p = 0.0003) and high systolic blood pressure (DeltaSBP) (OR = 0.87, p =
      0.0011). Myocardial ischemia was not associated with HF. CONCLUSION: HF is
      associated with functional parameters, such as dyspnea on exertion, history of
      chest pain and lower METS. It is also associated with structural benchmark index
      of left ventricular mass. In addition, chronotropic incompetence does not appear
      to increase the chance of myocardial ischemia in non-elderly patients.

PMID- 22481644
TI  - A neural mechanism for coordinate transformation predicts pre-saccadic remapping.
AB  - Whenever we shift our gaze, any location information encoded in the retinocentric
      reference frame that is predominant in the visual system is obliterated. How is
      spatial memory retained across gaze changes? Two different explanations have been
      proposed: Retinocentric information may be transformed into a gaze-invariant
      representation through a mechanism consistent with gain fields observed in
      parietal cortex, or retinocentric information may be updated in anticipation of
      the shift expected with every gaze change, a proposal consistent with neural
      observations in LIP. The explanations were considered incompatible with each
      other, because retinocentric update is observed before the gaze shift has
      terminated. Here, we show that a neural dynamic mechanism for coordinate
      transformation can also account for retinocentric updating. Our model postulates
      an extended mechanism of reference frame transformation that is based on
      bidirectional mapping between a retinocentric and a body-centered representation
      and that enables transforming multiple object locations in parallel. The dynamic
      coupling between the two reference frames generates a shift of the retinocentric
      representation for every gaze change. We account for the predictive nature of the
      observed remapping activity by using the same kind of neural mechanism to
      generate an internal representation of gaze direction that is predictively
      updated based on corollary discharge signals. We provide evidence for the model
      by accounting for a series of behavioral and neural experimental observations.

PMID- 22481645
TI  - Binary Willshaw learning yields high synaptic capacity for long-term familiarity
      memory.
AB  - In this study, we investigate from a computational perspective the efficiency of
      the Willshaw synaptic update rule in the context of familiarity discrimination, a
      binary-answer, memory-related task that has been linked through psychophysical
      experiments with modified neural activity patterns in the prefrontal and
      perirhinal cortex regions. Our motivation for recovering this well-known learning
      prescription is two-fold: first, the switch-like nature of the induced synaptic
      bonds, as there is evidence that biological synaptic transitions might occur in a
      discrete stepwise fashion. Second, the possibility that in the mammalian brain,
      unused, silent synapses might be pruned in the long-term. Besides the usual
      pattern and network capacities, we calculate the synaptic capacity of the model,
      a recently proposed measure where only the functional subset of synapses is taken
      into account. We find that in terms of network capacity, Willshaw learning is
      strongly affected by the pattern coding rates, which have to be kept fixed and
      very low at any time to achieve a non-zero capacity in the large network limit.
      The information carried per functional synapse, however, diverges and is
      comparable to that of the pattern association case, even for more realistic
      moderately low activity levels that are a function of network size.

PMID- 22481646
TI  - HLA and skin cancer.
AB  - Skin cancer - melanoma and non melanoma - are common neoplasm with rising
      incidence over the last decades. It is an important public health problem. Its
      pathogenesis is not completely understood and the same happens with the genetic
      factors involved. The genes that encode the HLA are associated with some tumors
      and they may be responsible for one of the mechanisms that take part in the
      development of the before mentioned cancers. We have reviewed the literature on
      the subject of HLA antigens, melanoma and non melanoma skin cancer.

PMID- 22481647
TI  - Comparative clinical evaluation of efficacy and safety of a formulation
      containing ciclopirox 8% in the form of a therapeutic nail lacquer in two
      different posologies for the treatment of onychomycosis of the toes.
AB  - BACKGROUND: The use of topical antifungal agents in the treatment of
      onychomycosis is of great value in clinical practice as there are different
      limitations regarding the use of systemic treatment. OBJECTIVE: To evaluate the
      efficacy and safety of a nail lacquer formulation containing ciclopirox 8% in two
      different posologies: the traditional regimen (3/2/1) and a regimen of weekly
      use. METHODS: A blind, randomized, comparative trial which included 41 patients
      divided into 02 groups, with Group I using the nail lacquer once weekly and Group
      II using the traditional regimen (3/2/1). Both groups applied the medication for
      06 months. RESULTS: The species most frequently found in groups I and II were
      Trichophyton rubrum (55% and 61.9%) and Trichophyton mentagrophytes (30% and
      19%). There was a tendency to a higher level of treatment resistance by T.
      mentagrophytes infection in both groups, without any predilection for sex, age,
      proportion of the nail affected at the beginning of the study, duration of the
      clinical disease and quantity of nails affected per person. Both groups had
      significant levels of mycological cure, clinical response and therapeutic success
      and there was no statistically significant difference between groups I and II (p
      >0.05). CONCLUSION: The nail lacquer containing ciclopirox 8% was equally
      effective at a weekly dose when compared to the traditional dosing (3/2/1),
      allowing a more comfortable regimen.

PMID- 22481648
TI  - Assessment of quality of life of patients with leprosy reactional states treated
      in a dermatology reference center.
AB  - BACKGROUND: Disabilities and deformities resulting from reactive outbreaks of
      leprosy can cause many problems for the patients, interfering with their quality
      of life. OBJECTIVES: To assess the quality of life of patients with leprosy
      reactional states identified at the Reference Center in Belo Horizonte - MG.
      METHODS: This was an epidemiological cross-sectional descriptive and analytical
      study, involving 120 patients in treatment for leprosy reactional states, from
      December 2007 to March 2008, held at the Dermatology outpatients clinic of the
      Hospital Eduardo de Menezes from FHEMIG, BH. We used two instruments for the
      socio-demographic, economic and clinical variables and a generic instrument
      WHOQOL WHO. The data were tabulated in SPSS and analyzed using the mean score
      with the application of statistical tests (p <0.05). RESULTS: We found that the
      median age of the patients was 48 years, most were males, married, from cities
      around BH, with incomplete elementary school, retired or pensioner, and with a
      family income of two minimum wages. Most of them reported that the disease
      interfered a great deal with their professional activities and leisure. In the
      assessment of QoL, the lowest rating was observed in the physical domain and the
      highest was observed in the psychological and social relations. The internal
      consistency of WHO-QOL-bref was acceptable to the facets and domains.
      CONCLUSIONS: Leprosy causes suffering that goes beyond the pain and discomfort
      strictly related to the physical damage, with great social and psychological
      impact.

PMID- 22481649
TI  - Assessment of knowledge of skin cancer prevention and its relation with sun
      exposure and photo protection amongst gym academy members on the south of Santa
      Catarina, Brazil.
AB  - BACKGROUND: Skin cancer is the most frequent neoplasia in several parts of the
      world and also in Brazil. There is evidence of an increase in morbidity and
      mortality from skin cancer. Although the incidence of skin cancer is increasing,
      it is estimated that 45% of all preventable cancers worldwide are skin
      neoplasias. Several studies have emphasized the need for campaigns to encourage
      sun protection. OBJECTIVE: To assess the knowledge about skin cancer prevention
      and its association with sun exposure and photo protection in gym members.
      METHODS: We conducted a cross-sectional, descriptive and quantitative study
      during January to July 2009, including gym members of both sexes in the city of
      Criciuma. A self-administered questionnaire was used. The statistical analysis
      was conducted in a descriptive way in regards to the absolute and relative
      frequencies of the variables under study. RESULTS: Of the 317 questionnaires
      studied, 62% were from women and 38% from men. Skin types II and III
      predominated, and the average age was 27.6 years. 94.3% of the participants
      reported that they had heard about the risks of sun exposure, mostly in terms of
      skin cancer risk (80.8%). Most participants, especially women, reported some form
      of sun protective measure. CONCLUSION: The population studied, similar to that in
      other regions of Brazil and the world, is aware of the risks of excessive sun
      exposure and skin cancer prevention, but has not yet incorporated appropriate sun
      protection measures into their daily habits.

PMID- 22481650
TI  - The vegetal biomembrane in the healing of chronic venous ulcers.
AB  - BACKGROUND: The vegetal biomembrane has been used to treat cutaneous ulcers.
      OBJECTIVES: To assess the role of the vegetal biomembrane on the chronic venous
      ulcers treatment compared to treatment with collagenase cream. METHODS: Fourteen
      patients were selected to be treated with vegetal biomembrane and 7 with
      Fibrase((r)) (CONTROL), followed clinically and photographically by the Wound
      Healing Index by ImageJ during 120 days and biopsied on the 1(st) and 30(th) days
      for histological examination. RESULTS: The vegetal biomembrane was better in
      promoting healing of the ulcers, especially on the inflammatory phase, confirmed
      by abundant exudation and wound debridement than the CONTROL group, on the 30th
      day. There was a greater tendency to angiogenesis followed by re
      epithelialization with highest wound healing index on the 90(th) and 120(th)
      days. CONCLUSION: A combined analysis of clinical and histopathological findings
      suggests that the vegetal biomembrane acted as a factor inducing wound healing,
      especially on the inflammatory phase, confirmed by abundant exudation of the
      lesions promoting the transformation of the microenvironment of the chronic
      venous ulcers, and also stimulating angiogenesis and subsequent re
      epithelialization.

PMID- 22481651
TI  - Clinical, biometric and ultrasound assessment of the effects of daily use of a
      nutraceutical composed of lycopene, acerola extract, grape seed extract and
      Biomarine Complex in photoaged human skin.
AB  - BACKGROUND: The use of nutraceuticals has become frequent in the cutaneous
      approach to photoaging. OBJECTIVES: To assess the clinical efficacy of a
      nutraceutical product composed of lycopene, acerola extract, grape seed extract
      and Biomarine ComplexT in photoaged human skin. METHODS: 50 women, from 35 to 60
      years of age, phototypes I to III, were assessed. For 120 days, they associated
      the nutraceutical product with the use of a sunscreen FPS15. On days 0 (D0), 30
      (D30), 60 (D60), 90 (D90) and 120 (D120) they were evaluated and underwent
      Medical Assessments and Self-Assessment and cutaneous biometric analyses
      (corneometry, sebumetry and pH-metry) in the skin of the left zygomatic region
      and the upper medial side region of the left arm; on days 0 (D0), 30 (D30) and
      120 (D120) the skin of the same regions was analyzed by ultrasound. On days 0
      (D0) and 120 (D120) skin biopsies were performed in the areas where instrumental
      evaluation was performed (to evaluate collagen and elastic fibers). RESULTS:
      There was an improvement of the general status of the skin of all volunteers by
      the Medical and Volunteer Self- Assessments; increased parameters of cutaneous
      hydration, reduction of pH, increasing of ultrasound density and a histological
      increment of collagen and elastic fibers (both on the face and arm); there was a
      reduction of seborrhea (only on the face) CONCLUSIONS: The daily use of a
      nutraceutical product containing lycopene, acerola extract, grape seed extract
      and Biomarine ComplexT showed an important adjuvant effect to counteract skin
      photoaging.

PMID- 22481652
TI  - Localized scleroderma: assessment of the therapeutic response to phototherapy.
AB  - BACKGROUND: Scleroderma is a chronic autoimmune disease characterized by
      progressive connective tissue sclerosis and microcirculatory changes. Localized
      scleroderma is considered a limited disease. However, in some cases atrophic and
      deforming lesions may be observed that hinder the normal development. Literature
      reports indicate phototherapy as a therapeutic modality with favorable response
      in cutaneous forms of scleroderma. OBJECTIVES: This study had the purpose of
      assessing the phototherapy treatment for localized scleroderma. METHODS: Patients
      with localized scleroderma were selected for phototherapy treatment. They were
      classified according to the type of localized scleroderma and evolutive stage of
      the lesions. Clinical examination and skin ultrasound were used to demonstrate
      the results thus obtained. RESULTS: Some clinical improvement was observed after
      an average of 10 phototherapeutic sessions. All skin lesions were softer at
      clinical palpation with scores reduction upon pre and post treatment comparison.
      The ultrasound showed that most of the assessed lesions presented a decrease in
      dermal thickness, and only five maintained their previous measure. Treatment
      response was similar regardless of the type of phototherapeutic treatment
      employed. CONCLUSIONS: The proposed treatment was effective for all lesions,
      regardless of the phototherapeutic modality employed. The improvement was
      observed in all treated skin lesions and confirmed by clinical evaluation and
      skin ultrasound.

PMID- 22481653
TI  - Topical estradiol does not interfere with the expression of the metalloproteinase
      1 enzyme in photo exposed skin cells.
AB  - BACKGROUND: In postmenopausal women there is a rapid destruction of dermal
      collagen, resulting in accelerated skin ageing, which is manifested by cutaneous
      atrophy, increased number and depth of wrinkles and sagging. This accelerated
      catabolism of the collagen is due to estrogen deficiency and increased synthesis
      of the metalloproteinase-1 enzyme, which degrades the dermal collagen.
      OBJECTIVES: To assess whether the use of topical estradiol 0.05% cream on photo
      exposed skin can inhibit the expression of the metalloproteinase-1 enzyme on the
      dermis and subsequently the rapid loss of collagen in women after menopause.
      METHODS: We included 40 postmenopausal women without hormone replacement therapy.
      Information about lifestyle, lipid profile, blood glucose level, thyroid
      hormones, mammography, Pap smear and transvaginal ultrasound were obtained to
      rule out associated diseases. Skin biopsy of the right preauricular region was
      performed before and after treatment with topical estradiol 0.05% for 30 days.
      The biopsy specimens were subjected to immunohistochemistry to identify the
      expression of the metalloproteinase-1 enzyme. RESULTS: There was no statistically
      significant difference on the expression of the metalloproteinase-1 enzyme in
      keratinocytes, fibroblasts and endothelial cells before and after treatment with
      topical estradiol for 30 days. CONCLUSION: Treatment with estradiol 0.05% cream,
      in photo exposed skin for 30 days, does not inhibit the production of
      metalloproteinase-1.

PMID- 22481654
TI  - Risk factors for syphilis in young women attending a family health program in
      Vitoria, Brazil.
AB  - BACKGROUND: The high prevalence of STDs among women indicates the need to
      implement approaching techniques, case detection and prevention of new cases.
      OBJECTIVES: To describe the frequency of risk factors for syphilis and assess
      attitudes towards sexual risk in a population of young women in Vitoria, ES.
      METHODS: Cross-sectional, population-based study, performed in Vitoria.
      Interviews were held and VDRL and MHA-TP were investigated in blood samples.
      RESULTS: Among the 904 eligible women (18-29 years) sampled from the Family
      Health Program (FHP), 11 were diagnosed with syphilis, a prevalence of 1.2%
      (CI95% 0.5-1.9). Median age was 23 years (interquartile range 20-26 years); 65.7%
      of participants were in high school or college and 85.4% lived with their family
      or sexual partner. Factors associated with syphilis included: lower educational
      level (<8 years of schooling) [Adjusted Odds Ratio aOR=4.3 (CI 95% 1.01-17.99)];
      >1 lifetime sexual partners [(aOR) =6.50 (CI95% 1.37-30.82)], and history of a
      previously diagnosed STD [aOR=10.3 (CI95% 2.37-44.33)]. Two thirds (67.7%) of the
      women surveyed agreed that it is not easy to tell their sexual partner they do
      not want to have sex without condoms; 52.3% thought it is difficult to use
      condoms in all sexual intercourses, and 36.2% said they cannot do anything if
      their partner refuses to use condoms. CONCLUSIONS: Using the FHP as an approach
      to perform routine VDRL can contribute to decreasing the vulnerability of these
      women and help control congenital syphilis.

PMID- 22481655
TI  - Papillary atrophy of the tongue and nutritional status of hospitalized
      alcoholics.
AB  - BACKGROUND: Atrophy of the papillae, mucosa, and dorsum of the tongue are
      considered classical signs of nutritional deficiencies. OBJECTIVE: To assess the
      nutritional status of hospitalized alcoholics with or without papillary atrophy
      of the tongue. METHODS: This study was performed with 21 hospitalized alcoholics
      divided into Atrophic Glossitis Group (n=13) and Normal Tongue Group (n=8).
      Healthy, non-alcoholic volunteers composed the Control Group (n=8). Anthropometry
      and bioelectric impedance were performed, and serum vitamins A, E, and B12 were
      determined. RESULTS: There were no statistical differences in relation to age
      (46.7 +/- 8.7 vs. 46.8 +/- 15.8 years) or gender (92.3% vs. 87.5% male),
      respectively. Control Group volunteers were also paired in relation to age (47.5
      +/- 3.1 years) and male predominance (62.5%). In relation to hospitalized
      alcoholics without atrophic lesions of the tongue and Control Group, patients
      with papillary atrophy showed lower BMI (18.6 +/- 2,5 vs 23.8 +/- 3.5 vs 26.7 +/-
      3,6 kg/m(2)) and body fat content 7.6 +/- 3.5 vs 13.3 +/- 6.5 vs 19.5 +/- 4,9
      kg). When compared with the Control Group, alcoholic patients with or without
      papillary atrophy of the tongue showed lower values of red blood cells (10.8 +/-
      2.2 vs 11.8 +/- 2.2 vs 14.5 +/- 1,6g/dL) and albumin (3.6 +/- 0.9 vs 3.6 +/- 0.8
      vs 4.4 +/- 0.2g/dL). The seric levels of vitamins A, E, and B12 were similar
      amongst the groups. CONCLUSION: Hospitalized alcoholics with papillary atrophy of
      the tongue had lower BMI and fat body stores than controls, without associated
      hypovitaminosis.

PMID- 22481656
TI  - Sun exposure and sun protection habits in high school students from a city south
      of the country.
AB  - BACKGROUND: Effective solar protection is an uncommon practice among young
      people, increasing the likelihood of sunburn, sunstroke and skin cancers. This
      fact is more significant in the south of Brazil, where the prevalence of white
      skinned population is larger, being more prone to sun damage. OBJECTIVES: To
      study the practices of sun exposure and sun protection in high school students
      from the city of Carlos Barbosa - RS. METHODS: Cross-sectional study involving
      775 students, enrolled on the first half of 2010, who had signed the consent
      form. We used a non-identifiable, self-administered questionnaire, with questions
      about related topics. Statistical analysis was performed using Chi-square or
      Fisher exact and t-Student tests. The study was approved by the Research Ethics
      Committee under the number 2010-115H. RESULTS: Most students are exposed to the
      sun at the more critical periods, remaining exposed for more than an hour. Five
      hundred and seventy-six students (74,3%) reported using sunscreen, but less than
      10% did it during all months of the year. Female teenagers are most likely to use
      sunscreen (p <0.001) and to spend less time exposed to sunlight (p <0.001).
      CONCLUSION: Most high school students from Carlos Barbosa had unsuitable sun
      exposure and sun protection habits, characterizing a high risk behavior for skin
      diseases. The existence of public programs for clarification of the risks to the
      population and the subsidization of sun protection products were suggested by
      these young people.

PMID- 22481657
TI  - Association of acanthosis nigricans and skin tags with insulin resistance.
AB  - Insulin resistance is a metabolic disorder in which target cells fail to respond
      to normal levels of circulating insulin. Insulin resistance has been associated
      with presence of acanthosis nigricans and acrochordons. It is known that early
      diagnosis and early initial treatment are of paramount importance to prevent a
      series of future complications. These dermatoses may represent an easily
      identifiable sign of insulin resistance and non-insulin-dependent diabetes.

PMID- 22481658
TI  - Actinic cheilitis and squamous cell carcinoma of the lip: clinical,
      histopathological and immunogenetic aspects.
AB  - Actinic cheilitis is the main precancerous lesion of the lip. Squamous cell
      carcinoma of the lip is reported together with oral carcinomas in the Brazilian
      official statistics. Overall, they account for 40% of the head and neck
      carcinomas. In general, physicians and dentists know little about what causes
      oral tumor development and progression. Tumor suppressor genes and cell
      proliferation regulatory proteins play a role in the progression of actinic
      cheilitis to squamous cell carcinoma and in its biological behavior. Knowledge on
      prognostic and diagnostic markers has a positive impact on the follow-up of these
      patients.

PMID- 22481659
TI  - Assessment of completion of forms requesting skin biopsies.
AB  - BACKGROUND: Information contained in request forms for histopathological
      examinations is essential for interpreting tissue changes observed in microscopy.
      OBJECTIVE: To determine the adequacy of information provided on forms requesting
      skin biopsies. METHOD: Assessment, in two health institutions, of 647 forms
      requesting skin biopsies in order to determine the completeness on the forms of
      the clinical details/items considered necessary for undertaking skin biopsies.
      RESULTS: Of the total 18 items on the forms, 7 were found to relay complete
      information in under 10% of the forms and only 9 items were correctly completed
      in over 80% of the requests. CONCLUSION: We concluded that information on many of
      the essential items required for a correct interpretation of the
      anatomopathologic examination was missing from the request forms.

PMID- 22481660
TI  - Primary systemic amyloidosis associated with multiple myeloma.
AB  - This case report is about a 48-year-old female patient with systemic amyloidosis
      and multiple myeloma simultaneously. Amyloid cutaneous infiltrative lesions like
      papules, nodules, or plaques with a serous-hemorrhagic aspect were found in the
      eyelids, neck and retroauricular region, among others. She had presented
      intermittent papular lesions on the upper eyelids one year before, which worsened
      following local trauma. A local skin biopsy showed amorphous and eosinophilic
      substance in the dermis. Congo red staining confirmed the amyloid deposits.
      Abnormal exams: proteinuria (570 mg/24h), Bence-Jones proteinuria and clonal
      plasma cells (70%) found in myelogram. Following the diagnosis of multiple
      myeloma based on amyloid skin lesions, the patient was referred to the Hematology
      service and died 5 months after the diagnosis.

PMID- 22481661
TI  - Breast cancer: 2 case reports.
AB  - Breast cancer is the most frequently diagnosed life-threatening cancer in women
      and the leading cause of cancer death among them worldwide. It includes a
      heterogeneous collection of diseases with various histologically defined subsets,
      clinical presentations, responses to treatment and outcomes. We describe 2 cases
      of female patients with ductal breast carcinoma. Dermatologists may have an
      important role in diagnosing such diseases.

PMID- 22481662
TI  - Clinical variability in dystrophic epidermolysis bullosa and findings with
      scanning electron microscopy.
AB  - In dystrophic epidermolysis bullosa, the genetic defect of anchoring fibrils
      leads to cleavage beneath the basement membrane and its consequent loss. A 46
      year-old female patient presented blisters with a pretibial distribution
      associated with nail dystrophy. Her two children had hyponychia and anonychia,
      which affected all toe nails and the thumb, forefinger and middle finger. DNA
      sequencing identified in exon 75 of COL7A1 gene a pathologic mutation: c.6235G>A
      (p.Gly2079Arg). Immunomapping of a blister demonstrated collagen IV (basal
      membrane) in the blister roof and collagen VII in its floor, confirming
      dystrophic epidermolysis bullosa. Scanning electron microscopy of an inverted
      blister showed net-forming collagen attached to the blister roof . The
      variability found in this family has already been reported and confirms, on a
      clinical basis, the nail subtype as a dystrophic variant.

PMID- 22481663
TI  - Buschke -Loewenstein tumor: identification of HPV type 6 and 11.
AB  - The authors report a case of exuberant giant condyloma acuminatum of Buschke
      Loewenstein in a male patient, slow-growing, progressive and with locally
      destructive behavior in the inguinal, body of the penis, scrotum, perineal and
      perianal regions. After surgery he showed no signs of recurrence in 20 months of
      follow-up. The identification of HPV types 6 and 11 was performed using in situ
      hybridization.

PMID- 22481664
TI  - Severe cutaneous and arthritic psoriasis in patient with AIDS: a good outcome
      with therapy using etanercept.
AB  - We report the case of a patient with cutaneous and arthropathic psoriasis for
      eight years, whose sudden increased severity of the clinical picture led to a
      diagnosis of AIDS, emphasizing the importance of the specialist in the diagnosis
      of systemic diseases. The appropriate therapeutic interventions, including
      antiretroviral therapy and the immunobiological agent etanercept, enabled rapid
      improvement of symptoms and quality of life of the patient, besides contributing
      to delay in immunodeficiency progression.

PMID- 22481665
TI  - Psoriasis, lymphoma and etanercept: is there a correlation?
AB  - Psoriasis is a chronic inflammatory disease that can affect skin and joints.
      Their treatment varies depending on the severity and includes topical and
      systemic. Among the latter are the immunobiological that target the T cell We
      report a case that demonstrates the close relationship between psoriasis,
      lymphoma and biologic therapies.

PMID- 22481666
TI  - Pityriasis amiantacea: clinical-dermatoscopic features and microscopy of hair
      tufts.
AB  - Pityriasis Amiantacea, also known as pseudotinea amiantacea, is a clinical
      syndrome which affects the scalp, having a reaction pattern reported to occur in
      several inflammatory dermatoses. The authors seek to establish the correlation
      between its clinical, dermoscopic and light microscopy features through the
      analysis of scale- encrusted hair tufts submitted to histological processing.

PMID- 22481668
TI  - Borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis.
AB  - We describe a case of borderline tuberculoid leprosy associated with primary
      cutaneous histoplasmosis in a patient who presented at our hospital with skin
      lesions and joint complaints.

PMID- 22481669
TI  - Periungual leishmaniasis.
AB  - The vast majority of cases of cutaneous leishmaniasis are represented by limb
      injuries. A female patient, white, presented an ulcer with infiltrated borders
      located on the fourth finger of the left hand following occupational exposure in
      an area of native forest. Diagnosis of cutaneous leishmaniasis caused by
      Leishmania of the subgenus Viannia was confirmed. The patient failed to respond
      to treatment with antimony, but achieved clinical cure after this was associated
      with pentoxifylline. The case highlights the rarity of the periungual location of
      the leishmanial lesion and the difficulties encountered in therapy.

PMID- 22481670
TI  - Case for diagnosis.
AB  - Dyschromicum erythema perstans, or ashy dermatosis, is a rare chronic acquired
      skin disease characterized by gray hyperpigmented patches with erythematous
      borders. Its etiology is unknown and there is no specific treatment for the
      condition. We report a case of ashy dermatosis in a 41-year-old patient with
      extensive lesions on the trunk and limbs.

PMID- 22481671
TI  - Case for diagnosis.
AB  - Henoch-Schonlein Purpura (HSP) is the most common vasculitis in children. In the
      absence of significant renal disease it has an excellent prognosis. In the case
      described, HSP initially presented together with orchitis. This infrequent event
      required the exclusion of testicular torsion.

PMID- 22481672
TI  - Do you know this syndrome?
AB  - The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis)
      includes a group of findings characterized by bone lesions usually located on the
      anterior chest wall, often associated with skin lesions. We report the case of a
      47 years old patient, with osteochondritis at costoesternal and manubrium-sternal
      joints, besides of palmar-plantar pustulosis. The diagnosis is predominantly
      clinical and there are several treatment options described in the literature.

PMID- 22481673
TI  - Concordance between direct microscopy and fungical culture for the diagnostic of
      feet's onychomycosis.
AB  - Prospective study compared the agreement between the direct microscopy and
      fungical culture from subungueal samples of the patients with clinical suspicion
      of feet's onychomycosis. The agreement occurred in 56.1% of the exams with
      dermatophytes, in 52.4% by others fungi and in 90.4% of the negative cases, 0,54
      according to the Kappa's test. In 39.3% of the onychomycosis caused by
      dermatophytes and 31.8% by nondermatophytes, these were identificated only for
      direct microscopy. The direct microscopic showed more sensibility compared with
      the culture, being superior in 19.5% of the total sample and maintaining
      agreement with the culture in 71.5% of the sample.

PMID- 22481674
TI  - Spontaneous cure in a case of Tinea nigra.
AB  - The authors report a case (in Itajai, Santa Catarina State, Brazil) of tinea
      nigra in a 4-year-old female child which spontaneously healed. We discuss the
      clinical and epidemiological aspects of the mycosis and this rare case of
      spontaneous healing.

PMID- 22481675
TI  - Cross-sectional descriptive study of topical self-medication in a hospital
      dermatology department in the state of Sao Paulo.
AB  - Self-medication involves individuals or their carers administering a medical drug
      of their own choice for symptomatic relief and in the hope of a "cure", without
      seeking professional medical advice.The aim of this descriptive cross-sectional
      study conducted at the Dermatology Department of the Taubate University Hospital
      was to identify the occurrence of self-medication for the topical treatment of
      skin diseases in young people under 18, and to analyze the difficulties
      encountered in the clinical diagnosis of these individuals.We examined 29 cases
      of self-medication (from a total of 480 attendances). Although self-medication is
      a common practice in Brazil our study showed that users were not significantly
      harmed by it.

PMID- 22481676
TI  - Prevalence of dermatologic disorders in 15 patients with acromegaly.
AB  - Acromegaly is a chronic, insidious and rare disease, caused by hyper secretion of
      the growth hormone, which metabolic and trophic effects commonly result in
      cutaneous manifestations, sometimes preceding other clinical symptoms. The
      authors have assessed 15 patients with acromegaly and found dermatologic lesions
      in all of them, mainly skin thickening, acrochordons, epidermoid cysts,
      pseudoacanthosis nigricans, seborrheic keratosis, melanocytic naevi and
      lentiginous spots.

PMID- 22481677
TI  - Shark island pedicle flap for repairing of basal cell carcinoma.

PMID- 22481678
TI  - Another link in the chain.

PMID- 22481679
TI  - Diagnosis of adult-type hypolactasia/lactase persistence: genotyping of single
      nucleotide polymorphism (SNP C/T-13910) is not consistent with breath test in
      Colombian Caribbean population.
AB  - CONTEXT: Genotyping of single nucleotide polymorphism (SNP C/T(-13910)) located
      upstream of the lactase gene is used to determine adult-type hypolactasia/lactase
      persistence in North-European Caucasian subjects. The applicability of this
      polymorphism has been studied by comparing it with the standard diagnostic
      methods in different populations. OBJECTIVE: To compare the lactose hydrogen
      breath test with the genetic test in a sample of the Colombian Caribbean
      population. METHODS: Lactose hydrogen breath test and genotyping of SNP C/T(
      13910) were applied to 128 healthy individuals (mean age 35 +/- 1). A positive
      lactose hydrogen breath test was indicative of hypolactasia. Genotyping was done
      using polymerase chain reaction/restriction fragment length polymorphism. The
      kappa index was used to establish agreement between the two methods. RESULTS:
      Seventy-six subjects (59%) were lactose-maldigesters (hypolactasia) and 52
      subjects (41%) were lactose-digesters (lactase persistence). The frequencies of
      the CC, CT and TT genotypes were 80%, 20% and 0%, respectively. Genotyping had
      97% sensitivity and 46% specificity. The kappa index = 0.473 indicates moderate
      agreement between the genotyping of SNP C/T(-13910) and the lactose hydrogen
      breath test. CONCLUSION: The moderate agreement indicates that the genotyping of
      the SNP C/T(-13910) is not applicable to determine adult-type
      hypolactasia/lactase persistence in the population participating in this study.

PMID- 22481680
TI  - Effect of HFE gene polymorphism on sustained virological response in patients
      with chronic hepatitis C and elevated serum ferritin.
AB  - CONTEXT: Abnormal serum ferritin levels are found in approximately 20%-30% of the
      patients with chronic hepatitis C and are associated with a lower response rate
      to interferon therapy. OBJECTIVE: To determine if the presence of HFE gene
      mutations had any effect on the sustained virological response rate to interferon
      based therapy in chronic hepatitis C patients with elevated serum ferritin.
      METHODS: A total of 44 treatment naIve patients with histologically demonstrated
      chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38
      genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with
      interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks.
      RESULTS: Sustained virological response was defined as negative qualitative HCV
      RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by
      qualitative in house polymerase chain reaction with a limit of detection of 200
      IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with
      RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%)
      patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological
      response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of
      27 patients without HFE gene mutations (P = 0.002; exact Fisher test).
      CONCLUSION: Heterozigozity for H63D and/or C282Y HFE gene mutation predicts
      absence of sustained virological response to combination treatment with
      interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and
      serum ferritin levels above 500 ng/mL.

PMID- 22481681
TI  - Assessment of portal venous index as a non-invasive method for diagnosing liver
      fibrosis in patients with chronic hepatitis C.
AB  - CONTEXT: Hepatitis C is an important cause of chronic liver disease worldwide.
      The grading of hepatic fibrosis in chronic hepatitis C is important for better
      clinical management. However, until now, liver biopsy is the only test accepted
      for this purpose, despite their contraindications and complications. New methods
      for non-invasive assessment of hepatic fibrosis are under investigation. One
      proposal is the Doppler ultrasound, as a non-invasive, widely available and
      inexpensive. OBJECTIVE: To compare Doppler parameters of portal vein in patients
      with chronic hepatitis C with a healthy control group and to correlate these
      parameters with fibrosis degree obtained by liver biopsy. METHODS: Fifty patients
      with chronic hepatitis C submitted to liver biopsy and 44 healthy controls had
      Doppler of the portal vein performed, with the calculation of the portal venous
      index. We conducted a comparison between the averages of the two groups of portal
      venous index. For the correlation between portal venous index and fibrosis was
      employed the Spearman test. RESULTS: There was a difference between the average
      portal venous index between controls (0.33 +/- 0.07) and patients (0.23 +/- 0.09)
      with P<0.001. No difference was observed between the portal venous index in
      patients with chronic hepatitis C who have significant fibrosis or not. The
      correlation between the portal venous index and fibrosis degree was reverse and
      moderate (r =-0.448 P<0.001). The area under the ROC curve was 78.4% (95% CI:
      68.8% to 88%). The cutoff for the portal venous index was 0.28 with sensitivity
      of 73.5% and specificity of 71.1%. CONCLUSION: The portal venous index was useful
      in distinguishing healthy patients from patients with CHC. However, there was no
      significant difference in the quantification of degree of fibrosis.

PMID- 22481682
TI  - Nutritional assessment in patients with cirrhosis.
AB  - CONTEXT: Malnutrition in cirrhotic patients with end-stage disease is common, and
      the degree of nutritional debilitation can play an important role in the
      pathogenesis of complications and cause a negative impact on prognosis. However,
      it involves difficulties and controversies regarding the identification of the
      best nutritional assessment method. OBJECTIVE: To identify a method that provides
      a safe and effective nutritional diagnosis. METHODS: Cross-sectional study with
      129 cirrhotic patients. Anthropometric measurements, subjective global
      assessment, hand grip strength and bioelectrical impedance. RESULTS: Through
      phase angle of bioelectrical impedance analysis (BIA) method, significant
      associations with Child-Pugh (P = 0.008), age group and gender were observed. The
      ROC (receiver operator characteristic) curve was generated to determine the best
      cutoff point of the phase angle of cirrhotic patients, serving as one of the
      reference parameters for the nutritional assessment with bioimpedance in this
      study, considering the classification through Child-Pugh score as the reference
      standard for the clinical conditions of patients with cirrhosis. CONCLUSIONS: The
      assessment through bioelectrical impedance presented a statistically significant
      correlation with Child-Pugh score. The identification of phase angle of 5.44o is
      the new parameter suggested for the classification of the nutritional conditions
      of cirrhotic patients.

PMID- 22481683
TI  - Investigation of nutritional risk factors using anthropometric indicators in
      hospitalized surgery patients.
AB  - CONTEXT: The investigation of risk factors associated with nutritional status
      could contribute for better knowledge of the malnutrition. OBJECTIVE: To
      investigate the incidence of malnutrition and its possible association with many
      parameters that assess nutritional status and to identify the associated risk
      factors. METHODS: The nutritional status was assessed in 235 hospitalized
      patients. Malnutrition was defined as present when the patient presented at least
      two anthropometric criteria below the normal range and habitual energy intake
      below 75% of the energy requirement (HEI/ER<75%). Gender, age, type of disease,
      recent weight change and dental problems were investigated as possible associated
      risk factors. The chi-square and Mann-Whitney tests were used to compare the data
      and univariate and multiple logistic regressions were used to identify the
      factors associated with malnutrition. The odds ratio (OR) and confidence interval
      (CI) of 95% were calculated with the significance level set at 5% (P<0.05).
      RESULTS: One-fifth (20%) of the patients were malnourished on admission to the
      hospital and 27.5% reported recent weight loss. Malnutrition (P<0.0001) was
      greater in patients with malignant diseases. The only variables significantly
      associated with malnutrition according to univariate logistic regression were
      recent weight loss (P = 0.0058; OR = 2.909; IC95% = 1.362; 6.212) and malignant
      disease (P = 0.0001; OR = 3.847; IC95% = 1.948; 7.597). When multiple regression
      was used in the model which included type of disease, malignant disease was shown
      to increase the chance of malnutrition fourfold (P = 0.0002; OR = 3.855; IC95% =
      1.914; 7.766). When disease was excluded, recent weight loss also increased
      malnutrition fourfold (P = 0.0012; OR = 3.716; IC95% = 1.677; 8.236). CONCLUSION:
      Patients with a history of recent weight loss and those with malignant diseases
      are more susceptible to malnutrition.

PMID- 22481684
TI  - Immunohistochemical evaluation of p53 and Ki-67 proteins in colorectal adenomas.
AB  - CONTEXT: The appearance of adenomas and their progression to adenocarcinomas is
      the result of an accumulation of genetic changes in cells of the intestinal
      mucosa inherited or acquired during life. Several proteins have been studied in
      relation to the development and progression of colorectal cancer, including tumor
      protein p53 (p53) and antigen identified by monoclonal antibody Ki-67 (Ki-67).
      OBJECTIVE: To evaluate the expression of p53 and Ki-67 in colorectal adenomas and
      correlate the observed levels with clinical and pathologic findings. METHOD: The
      sample consisted of 50 adenomatous polyps from patients undergoing colonoscopy.
      After performing polypectomy, polyps were preserved in a formalin solution with
      10% (vol./vol.) phosphate buffer, submitted for routine preparation of sections
      and slides and stained with hematoxylin and eosin. For each adenoma we then
      performed immunohistochemistry to detect specific p53 and Ki-67 proteins using a
      streptavidin-biotin-peroxidase enzyme immunoassay. RESULTS: p53 was detected in
      18% of the adenomas. The average Ki-67 protein index (i.Ki-67) was 0.49. A
      statistically significant difference was observed in p53 (P = 0.0003) and Ki-67
      (P = 0.02) expression between adenomas with low- and high-grade dysplasia,
      particularly for p53. The expression of Ki-67 was greater in rectal adenomas than
      in colic adenomas (P = 0.02). No relationship was found between the expression of
      the two proteins in the sample. CONCLUSION: The p53 protein is expressed in a
      proportion of adenomas, while the Ki-67 protein was expressed in all adenomas.
      The expression of p53 was higher in adenomas with high-grade dysplasia. The
      expression of Ki-67 was higher in rectal adenomas and in adenomas with high-grade
      dysplasia.

PMID- 22481685
TI  - Common bile duct stones: analysis of the videolaparoscopic surgical treatment.
AB  - CONTEXT: About 9% of the Brazilian population has gallstones and the incidence
      increases significantly with aging. The choledocholithiasis is found around 15%
      of these patients, and a third to half of these cases presented as asymptomatic.
      Once the lithiasis in the common bile duct is characterized through
      intraoperative cholangiography, the laparoscopic surgical exploration can be done
      through the transcystic way or directly through choledochotomy. OBJECTIVE: To
      evaluate the results and outcomes of the laparoscopic treatment of common bile
      duct lithiasis. METHODS: Seventy consecutive patients were evaluated. They
      prospectively underwent the treatment of the lithiasis in the common bile duct
      and the exploration ways were compared according to the following parameters:
      criteria on their indication, success in the clearance, surgical complications.
      It was verified that about 1/2 of the choledocholithiasis carriers did not show
      any expression of predictive factors (clinical antecedents of jaundice and/or
      acute pancreatitis, compatible sonographic data and the pertaining lab tests).
      The laparoscopic exploration through the transcystic way is favored when there
      are no criteria for the practice of primary choledochotomy, which are: lithiasis
      in the proximal bile duct, large (over 8 mm) or numerous calculi (multiple
      calculosis). RESULTS: The transcystic way was employed in about 50% of the
      casuistic and the choledochotomy in about 30%. A high success rate (around 80%)
      was achieved in the clearance of the common bile duct stones through laparoscopic
      exploration. The transcystic way, performed without fluoroscopy or
      choledochoscopy, attained a low rate of success (around 45%), being 10% of those
      by transpapilar pushing of calculi less than 3 mm. The exploration through
      choledochotomy, either primary or secondary, if the latter was performed after
      the transcystic route failure, showed high success rate (around 95%). When the
      indication to choledochotomy was primary, the necessity for choledochoscopy
      through choledochotomy to help in the removal of the calculi was 55%. However,
      when choledochotomy was performed secondarily, in situations where the common
      bile duct diameter was larger than 6 mm, the use of choledochoscopy with the same
      purpose involved about 20% of the cases. There was no mortality in this series.
      CONCLUSION: The laparoscopic exploration of the common bile duct was related to a
      low rate of morbidity. Therefore, the use of laparoscopy for the treatment of the
      lithiasis in the common bile duct depends on the criteria for the choice of the
      best access, making it a safe procedure with very good results.

PMID- 22481686
TI  - Prevalence of upper digestive endoscopy and gastric histopathology findings in
      morbidly obese patients.
AB  - CONTEXT: The prevalence of obesity has been increasing in modern society. Roux-en
      y gastric bypass is a bariatric surgery that involves the exclusion of
      significant part of the stomach. Atrophy, intestinal metaplasia and gastric
      cancer have been associated with infection by Helicobacter pylori. OBJECTIVES: To
      evaluate the presence of endoscopy findings and histological changes in morbid
      obese patients for the presence of inflammatory cells, inflammatory activity,
      lymphoid hyperplasia, H. pylori infection, atrophy and intestinal metaplasia in
      the gastric mucosa. METHODS: Upper digestive endoscopy and gastric
      histopathological were studied in 126 obese patients in the preoperative
      evaluation for bariatric surgery. RESULTS: Upper digestive endoscopy
      abnormalities were diagnosed in 73/126 (57.9%) patients. In three patients (2.4%)
      the upper gastrointestinal endoscopy diagnosed gastric ulcer and one patient
      (0.8%) had duodenal ulcer. The histopathological from gastric biopsies of these
      obese patients showed 65.1% of mucosa inflammation, inflammatory activity in
      50.0%, infection by H. pylori in 53.2%, lymphoid hyperplasia in 50.0% and atrophy
      and/or intestinal metaplasia in 16.7%. CONCLUSIONS: In present study, with
      routine preoperative upper gastrointestinal endoscopy and histopathological
      examination, were detected 57.9% patients with endoscopy abnormalities, high
      prevalence of infection by H. pylori (53%) and 16.7% of gastric atrophy and/or
      intestinal metaplasia.

PMID- 22481687
TI  - Helicobacter pylori eradication does not influence gastroesophageal reflux
      disease: a prospective, parallel, randomized, open-label, controlled trial.
AB  - CONTEXT: Helicobacter pylori has been associated with worsening of
      gastroesophageal reflux disease (GERD). OBJECTIVE: To evaluate the effect of H.
      pylori eradication in GERD patients. METHODS: We conducted a prospective,
      randomized, controlled trial performing symptom evaluation, endoscopy, histology,
      manometry and esophageal pH testing on GERD patients. Patients infected with H.
      pylori were randomized to: 1) eradication treatment plus proton pump inhibitors
      treatment, or 2) proton pump inhibitors alone. Patients not infected constituted
      a negative control group. After 3 months, patients were re-evaluated by symptom
      assessment, endoscopy, histology and manometry. RESULTS: GERD treatment resulted
      in significantly higher lower esophageal sphincter pressure, as measured by mean
      expiratory pressure, in H. pylori negative patients. There was significantly
      lower proportion of hypotensive waves and significantly higher proportion of
      normotensive waves in non-eradicated patients. All symptom scores were
      significantly reduced in the post-treatment period compared to baseline, to
      values that were similar among the three groups, in the post-treatment period. In
      the post-treatment period, erosive esophagitis was significantly less frequent on
      those not eradicated. CONCLUSION: Manometric, clinical and endoscopic data showed
      no benefit in eradicating H. pylori in GERD. Our data supports the hypothesis
      that H. pylori eradication does not influence GERD.

PMID- 22481688
TI  - Esophageal manometry findings and degree of acid exposure in short and long
      Barrett's esophagus.
AB  - CONTEXT: Barrett's esophagus (BE) is characterized by intestinal metaplasia in
      the distal esophagus and is classified as short-segment (<3 cm - SSBE) or long
      segment (>3 cm - LSSBE). It is suggested that LSSBE is associated with more
      severe esophageal motor abnormalities and increased acid exposure time than SSBE.
      OBJECTIVE: To evaluate the prevalence of esophageal manometriy abnormalities and
      acid exposure times in patients with SSBE and LSSBE. METHODS: Barrett's esophagus
      patients identified by upper endoscopy and confirmed by histopathology were,
      retrospectively, reviewed and divided into two groups: SSBE and LSBE. Demographic
      data, symptom duration, prevalence of hiatal hernia, lower esophagus sphincter
      basal pressure, prevalence of esophageal body abnormalities and acid exposure
      times were evaluated. RESULTS: Forty-six patients with SSBE (24 males - 52.2%,
      mean age of 55.2 years) and 28 patients with LSBE (18 males - 64.3%, mean age of
      50.5 years). Mean symptom duration was 9.9 years for SSBE and 12.9 years for
      LSSBE. Hiatal hernia was present in 84.2% of SSBE, 96.3% of LSBE; average lower
      esophagus sphincter pressure in SSBE 9.15 mm Hg, in LSBE 6.99 mm Hg; lower
      esophagus sphincter hypotension in SSBE was 65.9%, in LSSBE 82.1%; aperistalsis
      in SSBE 6.5%, LSSBE 3.6%; mild/moderate ineffective esophageal motility in SSBE
      34.8%, LSBE 46.4%; severe moderate ineffective esophageal motility in SSBE 10.9%,
      LSBE 7,1%; nutcracker esophagus/segmental nutcracker esophagus in SSBE 8.6%, LSBE
      0%; normal body in SSBE 39.1%, in LSBE 42.9%, no statistical difference for any
      of these values (P<0.05). Average % total time pH<4 in SSBE 9.12, LSBE 17.27
      (P<0.000); % time pH<4 upright in SSBE 11.91; LSBE 24.29 (P=0.003); % time pH<4
      supine in SSBE 10.86, LSBE 33.26 (P = 0.000). CONCLUSION: There was no difference
      between the prevalence of motor disorders in patients with SSBE and LSSBE. Acid
      reflux in upright and supine positions was more intense in LSBE.

PMID- 22481689
TI  - Portal vein thrombosis in children and adolescents: 20 years experience of a
      pediatric hepatology reference center.
AB  - CONTEXT: Portal vein thrombosis refers to a total or partial obstruction of the
      blood flow in this vein due to a thrombus formation. It is an important cause of
      portal hypertension in the pediatric age group with high morbidity rates due to
      its main complication - the upper gastrointestinal bleeding. OBJECTIVE: To
      describe a group of patients with portal vein thrombosis without associated
      hepatic disease of the Pediatric Hepatology Clinic of the Hospital das Clinicas,
      Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil with emphasis on
      diagnosis, presentation form and clinical complications, and the treatment of
      portal hypertension. METHODS: This is a descriptive study of a series of children
      and adolescents cases assisted from January 1990 to December 2010. The portal
      vein thrombosis diagnosis was established by ultrasound. RESULTS: Of the 55
      studied patients, 30 (54.5%) were male. In 29 patients (52.7%), none of the risk
      factors for portal vein thrombosis was observed. The predominant form of
      presentation was the upper gastrointestinal bleeding (52.7%). In 20 patients
      (36.4%), the initial manifestation was splenomegaly. During the whole following
      period of the study, 39 patients (70.9%) showed at least one episode of upper
      gastrointestinal bleeding. The mean age of patients in the first episode was 4.6
      +/- 3.4 years old. The endoscopic procedure carried out in the urgency or
      electively for search of esophageal varices showed its presence in 84.9% of the
      evaluated patients. The prophylactic endoscopic treatment was performed with
      endoscopic band ligation of varices in 31.3% of patients. Only one died due to
      refractory bleeding. CONCLUSIONS: The portal vein thrombosis is one of the most
      important causes of upper gastrointestinal bleeding in children. In all non
      febrile children with splenomegaly and/or hematemesis and without hepatomegaly
      and with normal hepatic function tests, it should be suspect of portal vein
      thrombosis. Thus, an appropriate diagnostic and treatment approach is desirable
      in an attempt to reduce morbidity and mortality.

PMID- 22481690
TI  - Hepatic hyperplasia and damages induces by zearalenone Fusarium mycotoxins in
      BALB/c mice.
AB  - CONTEXT: Zearalenone is a mycoestrogen and considered a mycotoxin. OBJECTIVE: To
      establish whether zearalenone produced hepatotoxicity via oral administration.
      METHODS: Zearalenone was orally administered at a dose of 50 mg, 100 mg and 200
      mg ZEN/body weight/daily, respectively, for 14 days to three groups of BALB/c
      mice. Diagnostic modalities used to evaluate hepatic damage and impaired hepatic
      function pre- and post zearalenone administration included hepatic marker enzyme
      activity, pentobarbital sleeping time, cytochrome P-(450) activities and
      histopathologic evaluation of liver. RESULTS: Significant histopathologic changes
      viz. sinusoidal congestion, cytoplasmic vacuolization, hepatocellular necrosis
      and neutrophil infiltration were observed after evaluating of liver section from
      each group after accumulated zearalenone exposure. Further, zearalenone exposure
      increased activities of alanine transaminase, aspartate transaminase and lipid
      peroxides whereas activities of tissue glutathione and cytochrome P(450) were
      decreased as compared to control mice. Zearalenone also increased the sleeping
      time and decreased sleeping latency after pentobarbital through intraperitoneal
      route as compared to control mice which indicates that the impairment of hepatic
      metabolizing enzymes by zearalenone. CONCLUSION: Zearalenone is a potential
      hepatotoxin by oral route.

PMID- 22481691
TI  - Noise-induced gastric lesions: a light and electron microscopy study of the rat
      gastric wall exposed to low frequency noise.
AB  - CONTEXT: Only a few studies evaluated the digestive alterations caused by low
      frequency noise (LFN) and most focused only on mucosal alterations. OBJECTIVES:
      To investigate the morphological injury of LFN-exposed gastric wall, beyond the
      epithelial layer. METHODS: Wistar rats were exposed to low frequency noise (LFN),
      during increasing periods, 1 to 13 weeks. A control group was kept in silence.
      Gastric specimens were studied using: (i) light microscopy with hematoxylin-eosin
      and immunostaining for collagens; (ii) transmission electron microscopy; (iii)
      morphometry allowing statistical analysis. RESULTS: Submucosa of all LFN-exposed
      animals exhibit increased thickness with fibrous proliferation. Transmission
      electron microscopy showed massive collagen deposition. Immunostaining identified
      collagen IV as responsible for the increased thickness. Morphometry allowed the
      demonstration of a significant difference of thickness between control and
      exposed groups. Vascular alterations included: i) intima proliferation and
      thickening, rupture of the internal elastic lamina, thrombotic changes; ii)
      thickening of the media; iii) after 9 weeks of LFN-exposure, we found new formed
      vessel presenting tortuous and twisted. There is a significant difference of
      arterial wall thickness between control and exposed groups. CONCLUSIONS: Deeper
      layers of gastric wall undergo alterations, including fibrosis of the submucosa
      caused by collagen IV deposition, an early marker of neoangiogenesis. Vascular
      alterations included thickening and thrombotic phenomena, but also images of
      newly formed vessels. This study suggests that, at least in the stomach, LFN
      induced fibrosis could be linked with neoangiogenesis.

PMID- 22481692
TI  - Metabolic syndrome and risk factors for non-alcoholic fatty liver disease.
AB  - CONTEXT: Non-alcoholic fatty liver disease (NAFLD), hepatic manifestation of
      metabolic syndrome, has been considered the most common liver disease nowadays,
      which is also the most frequent cause of elevated transaminases and cryptogenic
      cirrhosis. The greatest input of fatty acids into the liver and consequent
      increased beta-oxidation contribute to the formation of free radicals, release of
      inflammatory cytokines and varying degrees of hepatocytic aggression, whose
      histological expression may vary from steatosis (HS) to non-alcoholic
      steatohepatitis (NASH). The differentiation of these forms is required by the
      potential risk of progression to cirrhosis and development of hepatocellular
      carcinoma. OBJECTIVE: To review the literature about the major risk factors for
      NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and
      prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed
      to identify studies describing the link between risk factors for metabolic
      syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty
      liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk
      factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis
      and systematic reviews of great impact and scientific relevance to the topic,
      were selected. RESULTS: The final analysis of all these data, pointed out the
      central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk
      factors related to NAFLD. However, other factors were highlighted, such as gender
      differences, ethnicity, genetic factors and the role of innate immunity system.
      How these additional factors may be involved in the installation, progression and
      disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context
      of metabolic syndrome expands the prospects to 1) recognize patients with
      metabolic syndrome at high risk for NAFLD, 2) elucidate pathways common to other
      co-morbidities, 3) determine risk factors associated with a worse prognosis, 4)
      develop therapeutic strategies with goal of reducing risk factors, 5) apply
      acquired knowledge in public health policies focusing on preventive strategies.

PMID- 22481693
TI  - Exercise training program based on minimum weekly frequencies: effects on blood
      pressure and physical fitness in elderly hypertensive patients.
AB  - BACKGROUND: Exercise training (ET) can reduce blood pressure (BP) and prevent
      functional disability. However, the effects of low volumes of training have been
      poorly studied, especially in elderly hypertensive patients. OBJECTIVES: To
      investigate the effects of a multi-component ET program (aerobic training,
      strength, flexibility, and balance) on BP, physical fitness, and functional
      ability of elderly hypertensive patients. METHODS: Thirty-six elderly
      hypertensive patients with optimal clinical treatment underwent a multi-component
      ET program: two 60-minute sessions a week for 12 weeks at a Basic Health Unit.
      RESULTS: Compared to pre-training values, systolic and diastolic BP were reduced
      by 3.6% and 1.2%, respectively (p<0.001), body mass index was reduced by 1.1%
      (p<0.001), and peripheral blood glucose was reduced by 2.5% (p=0.002). There were
      improvements in all physical fitness domains: muscle strength (chair-stand test
      and elbow flexor test; p<0.001), static balance test (unipedal stance test;
      p<0.029), aerobic capacity (stationary gait test; p<0.001), except for
      flexibility (sit and reach test). Moreover, there was a reduction in the time
      required to perform two functional ability tests: "put on sock" and "sit down,
      stand up, and move around the house" (p<0.001). CONCLUSIONS: Lower volumes of ET
      improved BP, metabolic parameters, and physical fitness and reflected in the
      functional ability of elderly hypertensive patients. Trial Registration RBR
      2xgjh3.

PMID- 22481694
TI  - Attitudes and beliefs of Brazilian physical therapists about chronic low back
      pain: a cross-sectional study.
AB  - OBJECTIVES: To measure the attitudes and beliefs of Brazilian physical therapists
      about chronic low back pain and to identify the sociodemographic characteristics
      that are more likely to influence these attitudes and beliefs. METHODS: We
      conducted a cross-sectional study with 100 Brazilian physical therapists who
      routinely work with chronic low back pain patients. The attitudes and beliefs
      were measured by the Pain Attitudes and Beliefs Scale for Physiotherapists
      (PABS.PT) and the Health Care Providers' Pain and Impairment Relationship Scale
      (HC-PAIRS). Multivariate linear regression models were built to identify
      sociodemographic characteristics that could be associated with physical
      therapists' attitudes and beliefs. RESULTS: Mean scores on the biomedical and
      biopsychosocial factors of PABS.PT were 27.06 (SD 7.19) and 24.34 (SD 6.31),
      respectively, and the mean score on HC-PAIRS was 45.45 (SD 10.45). The score on
      PABS.PT(biomedical) was associated with gender and years of professional
      experience. No variable was associated with the score on
      PABS.PT(biopsychosocial). The score on HC-PAIRS was significantly associated with
      the number of back pain patients seen by the physical therapist each month. These
      results indicate that male and less experienced physical therapists tend to
      follow a biomedical approach to the treatment of chronic low back pain patients,
      and that the lower the professional experience the stronger the belief in the
      relationship between pain and disability. CONCLUSIONS: Brazilian physical
      therapists are uncertain of the factors involved in the development and
      maintenance of chronic low back pain and about the relationship between pain and
      disability in these patients.

PMID- 22481695
TI  - Proposal of non-invasive experimental model to induce scoliosis in rats.
AB  - BACKGROUND: In the literature, there are several experimental models that induce
      scoliosis in rats; however, they make use of drugs or invasive interventions to
      generate a scoliotic curve. OBJECTIVES: To design and apply a non-invasive
      immobilization model to induce scoliosis in rats. METHODS: Four-week old male
      Wistar rats (85+/-3.3g) were divided into two groups: control (CG) and scoliosis
      (SG). The animals in the SG were immobilized by two vests (scapular and pelvic)
      made from polyvinyl chloride (PVC) and externally attached to each other by a
      retainer that regulated the scoliosis angle for twelve weeks with left convexity.
      After immobilization, the abdominal, intercostal, paravertebral, and pectoral
      muscles were collected for chemical and metabolic analyses. Radiographic reports
      were performed every 30 days over a 16-week period. RESULTS: The model was
      effective in the induction of scoliosis, even 30 days after immobilization, with
      a stable angle of 28+/-5o. The chemical and metabolic analyses showed a decrease
      (p<0.05) in the glycogenic reserves and in the relationship between DNA and total
      protein reserves of all the muscles analyzed in the scoliosis group, being lower
      (p<0.05) in the convex side. The values for the Homeostatic Model Assessment of
      Insulin Resistance indicated a resistance condition to insulin (p<0.05) in the
      scoliosis group (0.66+/-0.03), when compared to the control group (0.81+/-0.02).
      CONCLUSIONS: The scoliosis curvature remained stable 30 days after
      immobilization. The chemical and metabolic analyses suggest changes in muscular
      homeostasis during the induced scoliosis process.

PMID- 22481696
TI  - Effects of ELTGOL and Flutter VRP1(r) on the dynamic and static pulmonary volumes
      and on the secretion clearance of patients with bronchiectasis.
AB  - BACKGROUND: Although respiratory physical therapy is considered fundamental in
      the treatment of hypersecretive patients, there is little evidence of its
      physiological and therapeutic effects in bronchiectasis patients. OBJECTIVE: To
      evaluate the acute physiological effects of ELTGOL and Flutter VRP1(r) in dynamic
      and static lung volumes in patients with bronchiectasis and, secondarily, to
      study the effect of these techniques in sputum elimination. METHODS: Patients
      with clinical and radiological diagnosis of bronchiectasis were included.
      Patients underwent three interventions in a randomized order and with a one-week
      washout interval between them. Before all interventions patients inhaled two
      puffs of 100 mcg of salbutamol. There was a cough period of five minutes before
      and after the control protocol and the interventions (ELTGOL and Flutter
      VRP1(r)). After each cough series patients underwent assessments of dynamic and
      static lung volumes by spirometry and plethysmography. The expectorated
      secretions were collected during the interventions and during the second cough
      series, and quantified by its dry weight. RESULTS: We studied 10 patients, two
      males and eight females (mean age: 55.9+/-18.1 years). After using Flutter
      VRP1(r)and ELTGOL there was a significant decrease in residual volume (RV),
      functional residual capacity (FRC) and total lung capacity (TLC) (p<0.05). There
      was a higher sputum production during ELTGOL compared with Control and Flutter
      VRP1(r) (p<0.05). CONCLUSION: The ELTGOL and Flutter VRP1(r) techniques acutely
      reduced lung hyperinflation, but only the ELTGOL increased the removal of
      pulmonary secretions from patients with bronchiectasis.

PMID- 22481697
TI  - [The endovascular surgery and hybrid rooms?].

PMID- 22481698
TI  - Evidence-based telemedicine: trauma & acute care surgery (EBT-TACS).

PMID- 22481699
TI  - Pulmonary function, respiratory muscle strength and quality of life in patients
      submitted to elective thoracotomies.
AB  - OBJECTIVE: To evaluate pre-and postoperative pulmonary function, respiratory
      muscle strength and quality of life in patients submitted to elective
      thoracotomy. METHODS: We selected 19 patients undergoing elective thoracotomy to
      assess the following parameters: forced vital capacity (FVC), forced expiratory
      volume in one second (FEV1), maximal inspiratory pressure (MIP), maximal
      expiratory pressure (MEP) and quality of life through implementation of the SF
      36. The examinations were performed preoperatively and in the second, 10th, 15th,
      30th and 60th days postoperatively. We conduced data normality analyzes were made
      with the Shapiro-Wilk test, descriptive analysis of the study variables, as well
      as analysis of variance with multiple comparisons using ANOVA and Friedman, p
      value <0.05 . RESULTS: There was a significant decrease in spirometric levels and
      in maximal respiratory pressures in the second postoperative day. FVC returned to
      preoperative values between the 15th and 30th postoperative days, whereas FEV1,
      between the 10th and 15th. MIP and MEP returned to preoperative values between
      the 10th and 15th postoperative days. There was a decrease in quality of life as
      for functional capacity and physical aspects, which returned to preoperative
      values within two months after surgery. CONCLUSION: There was significant
      reduction in lung function and respiratory muscle strength, which returned to
      baseline within 30 days after surgery. There was a decrease in quality of life
      that persisted for up to 60 days after the operation.

PMID- 22481700
TI  - Evaluation of carotid artery intima-media complex thickness as a marker of
      vascular damage secondary to accelerated atherogenesis in progressive systemic
      sclerosis.
AB  - OBJECTIVE: To evaluate the intima-media thickness of the common carotid artery in
      patients with and without scleroderma; to verify a possible association with
      disease severity; to assess the relationship of intima-media thickness with known
      cardiovascular risk factors. METHODS: In a case-control study, were selected 30
      patients with scleroderma and 30 without the disease and matched according to
      age, sex and cardiovascular risk factors such as hypertension, diabetes mellitus
      and hypercholesterolemia. The age ranged from 17 to 79 years (mean 49). All
      patients underwent carotid artery evaluation by high-resolution vascular Doppler
      in order to measure the intima-medial thickness of the carotid 2 cm from the
      bifurcation. In all the analysis was considered the greatest value of intima
      media thickness in right and left carotid arteries. RESULTS: The sample consisted
      of 30 patients, being 29 (96.67%) women and one man (3.3%). In this sample, 11/30
      (36.67%) had high blood pressure, 5/30 (16.67%) had diabetes mellitus, 6/30 (20%)
      had dyslipidemia and 2/30 (6.67%) were smokers. Comparing the measure of the
      increased risk (maximum intima-media thickness between the left and right side),
      was obtained an average of 0.77 mm for group scleroderma and a value of 0.70 mm
      for the control group (p = 0.21). In assessing the association between disease
      severity and carotid intima-media thickness, was found no significant association
      (p= 0.925). CONCLUSION: Was found a slight increase in intima-medial thickness of
      common carotid artery in patients with scleroderma but without statistical
      significance. Regarding the severity of the disease and intima-medial thickness
      of common carotid artery, there was no significant difference.

PMID- 22481701
TI  - Vena cava filters: a decade of experience in a level I trauma center.
AB  - OBJECTIVE: To evaluate the data on the use of vena cava filter in the Division of
      Trauma, UCSD Medical Center - San Diego, CA / USA. METHODS: A descriptive study
      was conducted at the Division of Trauma to evaluate the cumulated experience and
      the therapeutic approach in patients attended by the staff of the Division of
      Trauma and submitted to placement of a vena cava filter as a method of prevention
      or treatment of Pulmonary Thromboembolism (PTE) from January 1999 to December
      2008. RESULTS: The study comprised 512 patients, mostly males (73%). As to the
      cause, automobile accident injuries predominated, followed by injuries caused by
      falls. The male / female ratio was 3:1. The most affected age group was the one
      between 21 to 40 years, representing 36% of patients. The percentage of
      prophylactic vena cava filters was 82%, whilst 18% had treatment purposes. Head
      trauma was the main cause for the indication of prophylactic filters followed by
      spinal cord trauma. The rate of pos-filter deep vein thrombosis (DVT) was 11%.
      CONCLUSION: In the presence of contraindications to the use of anticoagulants in
      patients who suffered severe trauma, the inferior vena cava filters have proven
      to be an effective and safe option. However, one should apply rigorous clinical
      judgment to all indications, even after the advent of retrievable filters.

PMID- 22481703
TI  - Development of an electronic protocol for uterine cervical cancer.
AB  - OBJECTIVE: Development of an electronic protocol for cancer of the cervix.
      METHODS: We collected data through a literature review and formatted them to
      build a theoretical base for cancer of the cervix for inclusion in the protocol.
      The computerized database used the SINPE (c) (Integrated Electronic Protocols)
      developed at the Federal University of Parana by the Graduate Program in Surgery,
      Department of Health Sciences, with the help of the Laboratory of Computer and
      Multimedia. RESULTS: We created 2,687 items, grouped into seven main categories:
      history, physical examination, laboratory tests, diagnosis, final pathology,
      treatment and monitoring. We added items on socio-demographic indicators,
      contraceptive use, smoking, gynecological and obstetrical histories, staging, the
      most widely accepted classifications and nomenclatures, diagnostic methods,
      treatments and follow-up. CONCLUSION: It is possible to develop an electronic
      protocol with low cost, little space and minimal staff training. The use of
      computers avoids limitations and the subjective character of written records.
      With the data collected in an appropriate manner it is possible to determine,
      through statistical analysis, the importance of each factor in cancer development
      and progression and prognosis.

PMID- 22481702
TI  - Perioperative mortality in diabetic patients undergoing coronary artery bypass
      graft surgery.
AB  - OBJECTIVE: To investigate the risk factors for in-hospital death in diabetic
      patients undergoing isolated Coronary Artery Bypass Grafting (CABG). METHODS: We
      conducted a retrospective study with 305 consecutive diabetic patients undergoing
      CABG in the Division of Cardiovascular Surgery of our institution from April 2004
      to April 2010. Univariate analysis for categorical variables was performed with
      the chi-square or Fisher's exact test, as appropriate. Potential risk factors
      with p <0.05 in the univariate analysis were included in the multivariate
      analysis, which was performed by backward logistic regression. Values of p <0.05
      were considered statistically significant. RESULTS: The study population had a
      mean age of 61.44 years (+/- 9.81) and 65.6% (n=200) were male. The in-hospital
      mortality rate was 11.8% (n=36). The following independent risk factors for death
      were identified: on-pump CABG (OR 6.15, 95% CI 1.57 to 24.03, P=0.009) and low
      cardiac output in the postoperative period (OR 34.17, 95% CI 10.46 to 111.62, P
      <0.001). The use of internal thoracic artery (ITA) was an independent protective
      factor for death (OR 0.27, 95% CI 0.08 to 0.093, P=0.038). CONCLUSION: This study
      identified the following independent risk factors for death after CABG: on-pump
      CABG and low cardiac output syndrome. The use of ITA was an independent
      protective factor.

PMID- 22481704
TI  - Evaluation of serum levels of interleukin-6 and interleukin-10 in patients
      undergoing laparoscopic versus conventional cholecystectomy.
AB  - OBJECTIVE: To correlate serum preoperative and postoperative interleukin-6 and
      interleukin-10 levels in patients undergoing laparotomy versus laparoscopic
      cholecystectomy. METHODS: From a total of 20 patients, 18 were included in the
      study, nine underwent cholecystectomy by laparoscopy and the other nine by
      laparotomy. Serum concentrations of IL-6 and IL-10 were measured in both groups.
      Blood samples were obtained in the times of 24 hours preoperatively and four, 12
      and 24 hours after the procedure. The groups were compared regarding age, gender,
      body mass index (BMI), duration of anesthesia and operation. RESULTS: There was
      no significant statistical differences between groups related to age, gender,
      BMI, duration of anesthesia and operation. The comparison between the two
      procedurs demonstrated statistical differences for IL-6 in time 12 hours after
      operation (218.64 pg/ml laparotomic versus 67.71 pg/ml laparoscopic, p = 0.0003)
      and for IL-10 in time 24 hours after the procedure (24.46 pg/ml open versus 10.17
      pg/qml laparoscopic, p <0.001). CONCLUSION: There was an Increase in plasma
      levels of interleukin-6 and 10 after surgical trauma with a significant increase
      in levels of interleukins in the laparotomic group in comparison with the
      laparoscopic group.

PMID- 22481705
TI  - Correlation analysis between post-pancreatoduodenectomy pancreatic fistula and
      pancreatic histology.
AB  - OBJECTIVE: To evaluate the relationship between the occurrence of pancreatic
      fistula after pancreatojejunal anastomosis in patients undergoing
      pancreaticoduodenectomy for periampullary malignancy and the histological
      fibrosis and inflammation found in pancreatic tissue and the caliber of the main
      pancreatic duct. METHODS: We conducted a retrospective study with patients that
      were treated with surgical resection. The rate of pancreatic fistulae was
      recorded. Histology classification was performed according to fibrosis and
      pancreatic inflammation. RESULTS: We identified 77 patients, mean age was 57.6
      years; 62.4% were male. As for the type of operation performed, 66.3% were
      gastroduodenopancreatectomies and 33.7% pancreatoduodenectomies with pylorus
      preservation. Regarding the number of fistulas diagnosed, it was found that 23.4%
      patients displayed this postoperative complication and in 66.7% the cause was
      cancer of the papilla. As for intraoperative macroscopic findings, we identified
      the classification of pancreatic texture, seen as normal in 85.8%, and the
      caliber of the main pancreatic duct, finding an average of 4.9 mm. There was a
      significant relationship between the hardened pancreatic stump and the absence of
      fistula. In patients with normal or soft tissue, the rate of fistula was 25.4%.
      Regarding ductal diameter, we identified a higher number of pancreatic
      anastomotic dehiscences in the absence of ductal dilation (p <0.05). We noticed
      that patients with an average ductal diameter of 5.4 mm (76.7%) did not show this
      complication. CONCLUSION: The presence of fibrosis and ductal dilation usually
      coexist and is related to a lower percentage of pancreatic fistulae.

PMID- 22481706
TI  - Evaluation of the expression of the MGMT gene in normal and neoplastic tissue of
      patients with colorectal cancer.
AB  - OBJECTIVE: To evaluate the expression of tissue repair gene MGMT by comparing
      normal and neoplastic colonic mucosa in patients with colorectal cancer (CRC).
      METHODS: We studied 44 patients with colorectal cancer confirmed by
      histopathology. We excluded patients suspected of belonging to families with
      hereditary colorectal cancer (HNPCC and FAP) and patients with cancer of the
      lower or medium rectum treated with neoadjuvant chemoradiotherapy. The MGMT gene
      expression was assessed by the technique of polymerase chain reaction in real
      time (RT-PCR). The comparison of results for MGMT gene expression between normal
      and neoplastic tissues was made by paired Student's t test, adopting a
      significance level of 5% (p <0.05). RESULTS: Tissue expression of the MGMT gene
      in all patients was lower in tumor tissue when compared to normal tissue (p =
      0.002). CONCLUSION: The repair gene MGMT is less expressed in tumor tissue
      compared to normal tissues in patients with sporadic CRC.

PMID- 22481707
TI  - Analysis of the use of fasciocutaneous flaps for immediate vulvar reconstruction.
AB  - OBJECTIVE: To analyze the use of immediate reconstruction techniques of the vulva
      after surgical resection, with fasciocutaneous flaps of the medial and/or
      posterior thigh. METHODS: We conducted a transversal, retrospective study to
      analyse the outcome of immediate surgical reconstruction with fasciocutaneous
      flaps in nine patients who underwent vulvectomy from May 2009 to August 2010.
      RESULTS: Mean age was 61 years (range 36-82). In 56% of cases, diagnosis was
      vulvar intraepithelial neoplasia (VIN), usual type. Radical vulvectomy was
      performed in 45% of patients, simple vulvectomy in 33% and wide resections in
      22%. Eleven fasciocutaneous flaps were made, of which 36.3% were flap
      transpositions from the posterior thigh, 18.2% from the medial thigh, 18.2% were
      in advancement flaps, 18.2% simple advancement flaps and 9.1% flap rotation from
      the posterior thigh. There were no major losses of the flaps made. CONCLUSION:
      Thigh fasciocutaneous flaps are currently the best options for immediate
      reconstruction after resection of vulvar cancer due to the preservation of
      sensibility and tissue availability in the donor areas. The association of the
      Plastic Surgeon with the Gynecologist offers tranquility for patients and
      provides good postoperative results.

PMID- 22481708
TI  - Vitamin D deficiency in patients with chronic venous ulcers.
AB  - OBJECTIVE: To study if the prevalence of vitamin D deficiency in patients with
      venous leg ulcer is higher than in the control population. METHODS: Serum levels
      of 25 hidroxi (OH)-vitamin D3 was studied by chemiluminescence in 27 patients
      with chronic venous ulcer and 58 controls at the Evangelical Hospital of
      Curitiba. RESULTS: The levels of 25 OH-vitamin D3 were below 8 ng/dl in 11.1% of
      ulcer patients and 3.4% of controls; between 8 and 20 ng/dl in 46.1% of ulcer
      patients and 25.8% of controls; between 21 and 30 ng/dl in 22.2% of ulcer
      patients and 27.5% of controls and above 30 ng/dl in 43.1% of controls and 18.5%
      of ulcer patients (p=0.04). CONCLUSION: There is an increased prevalence of
      vitamin D deficiency in patients with chronic venous leg ulcers.

PMID- 22481709
TI  - [Surgical accesses to the major mediastinal vessels in thoracic trauma].
AB  - Trauma is the most common cause of death in the economically active population
      and thoracic trauma is directly or indirectly responsible for one quarter of
      these deaths. Lesions to the large thoracic vessels are associated with immediate
      or early death in the hospital setting. Patients admitted alive can be classified
      as stable or unstable. The access route to be elected for management of these
      veins will depend on this status, as well as on the anatomical particularities of
      the patient, which may require combined incisions for adequate access. This
      article provides a review and discussion of lesions to these structures as well
      as access routes to them.

PMID- 22481710
TI  - [Is the use of newly deceased ethically acceptable for teaching medical
      procedures?].
AB  - The use if newly deceased for teaching medical procedures occurs with an unknown
      frequency. In the surgical area the training of skills has a fundamental
      importance due to the need of invasive procedures inherent to the surgical
      practice. There are rare publications about this issue in Bioethics, but it is
      fundamental that this discussion and pondering be done in the surgery departments
      of the teaching hospitals. The performance of procedures in newly deceased must
      be faced as an exception and it must be mandatorily preceded by family
      authorization.

PMID- 22481711
TI  - Tranexamic acid for traumatic hemorrhage.

PMID- 22481712
TI  - [Adrenal ganglioneuroma].
AB  - Ganglioneuromas are rare, benign tumors arising from neural crest tissue. Their
      most frequent location is the posterior mediastinum, followed by the
      retroperitoneum. Only a small proportion are adrenal in origin. The authors
      report a case of a 24-year-old woman with inespecific symptoms of low back pain
      and presenting with an adrenal mass. An adrenalectomy was performed and the
      diagnosis of ganglioneuroma was confirmed.

PMID- 22481713
TI  - [Spontaneous rupture of the esophagus: Boerhaave's syndrome].
AB  - Boerhaave's syndrome, the spontaneous rupture of the esophagus, is associated
      with a 35% death rate. Perforated esophagus is a surgical emergency; it is the
      most serious, and frequently the most rapidly lethal, perforation of the gastro
      intestinal tract. Three cases of Boerhaave's syndrome are presented, with their
      variants and resolutions. Treatment and outcome are largely determined by the
      time of presentation. We reviewed our experience with esophageal perforations to
      determine the overall mortality and whether the time of presentation should
      influence management strategy.

PMID- 22481714
TI  - The violence and its implications for health and nursing.

PMID- 22481715
TI  - Nursing diagnoses in trauma victims with fatal outcomes in the emergency
      scenario.
AB  - The objective of this study was to identify and analyze the nursing diagnoses
      that constitute risk factors for death in trauma victims in the first 6 hours
      post-event. This is a cross-sectional, descriptive and exploratory study using
      quantitative analysis. A total of 406 patients were evaluated over six months of
      data collection in a tertiary hospital in the municipality of Sao Paulo,
      according to an instrument created for this purpose. Of the total, 44 (10.7%)
      suffered death. Multivariate analysis indicated the nursing diagnoses ineffective
      respiratory pattern, impaired spontaneous ventilation, risk of bleeding and risk
      of ineffective gastrointestinal tissue perfusion as risk factors for death and
      ineffective airway clearance, impaired comfort, and acute pain as protective
      factors, data that can direct health teams for different interventionist actions
      faced with the complexity of the trauma.

PMID- 22481716
TI  - A cross-sectional study of factors underlying the risk of female nurses'
      suffering abuse by their partners.
AB  - This study aimed to identify factors underlying the risk of suffering abuse by a
      partner. A cross-sectional study of 622 female nurses was accomplished, randomly
      chosen at their place of work, at a hospital and health centers. We used a self
      administered validated questionnaire that covered psychological, physical and
      sexual abuse, complemented by a set of sociodemographic questions. The nurses at
      most risk of being abused by their partners were those who supported their family
      by their own salary (Odds Ratio: 2.41 [0.63-9.15]), those who lived with
      dependents (Odds Ratio: 4.27 [1.43-2.78]) and had a partner from social class
      IIIa (Odds Ratio: 2.62 [1.37-5.00]). The data appear to indicate financial
      independence as a risk factor for this type of abuse.

PMID- 22481717
TI  - Work and Inter-subjectivity: a theoretical reflection on its dialectics in the
      field of health and nursing.
AB  - This theoretical reflection intends to show the inter-subjective relationship
      that takes place in health and nursing practices under the following theoretical
      perspectives: Institutional Analysis, Psychodynamics of Labor and the Theory of
      Communicative Action, with an emphasis on the latter. Linking these concepts to
      the Marxist approach to work in the field of health emerges from recognizing the
      need for its continuous reconstruction-in this case, with a view to understand
      the interaction and communication intrinsic to work in action. The theory of
      Communicative Action seeks to consider these two inextricable dimensions: work as
      productive action and as interaction. The first corresponds to instrumental
      action based on technical rules with a production-guided rationale. The second
      refers to the interaction that takes place as communicative action and seeks
      understanding among subjects. We assume that adopting this theoretical
      perspective in the analysis of health and nursing practices opens new
      possibilities for clarifying its social and historical process and inter
      subjective connections.

PMID- 22481718
TI  - Cross-cultural adaptation of the Work Disability Diagnosis Interview (WoDDI) for
      the Brazilian context.
AB  - The Work Disability Diagnosis Interview (WoDDI) is a structured interview guide
      developed by the University of Sherbrooke, Canada to help clinicians detect the
      most important work-related disability predictors and to identify one or more
      causes of prolonged absenteeism. This methodological study aims for the cross
      cultural adaptation of the WoDDI for the Brazilian context. The method followed
      international guidelines for studies of this kind, including the following steps:
      initial translation, synthesis of translations, back translation, evaluation by
      an expert committee and testing of the penultimate version. These steps allowed
      obtaining conceptual, semantic, idiomatic, experiential and operational
      equivalences, in addition to content validity. The results showed that the
      translated WoDDI is adapted to the Brazilian context and can be used after
      training.

PMID- 22481719
TI  - Application of a domicile-based exercise program for shoulder rehabilitation
      after breast cancer surgery.
AB  - The aim of this study was to evaluate the effectiveness of an exercise program
      for the recuperation of the range of motion (ROM) of the shoulder. This is a
      quasi-experimental study developed at the Mastology Outpatient Clinic of the
      Federal University of Sao Paulo - Brazil, from August 2006 to June 2008, with 64
      breast cancer patients undergoing surgery. The intervention consisted of:
      preoperative evaluation of the ROM, verbal and written guidance, demonstration
      and implementation of the exercises and revaluation at the outpatient follow-up
      appointments until the 105(th) postoperative day (PO). From the 7(th) PO a
      significant increase was observed in the ROM, which continued until the 105(th)
      PO. The minimum time for recovery was 105 days for the women undergoing
      mastectomy, and 75 days for those undergoing quadrantectomy. There was
      satisfactory adherence of 78.6% of the women. The domicile program was effective
      for the recovery of ROM in the study population, benefiting women who can not
      attend a presential program.

PMID- 22481720
TI  - Family health team knowledge concerning the health needs of people with
      tuberculosis.
AB  - The purposes of the study were to get to know conceptions on tuberculosis and
      health needs and to describe the care provided to people with tuberculosis,
      according to health professionals' perspective. Qualitative study developed at
      family health units in Capao Redondo, Sao Paulo. The data were collected through
      open interviews in January 2010 and submitted to discourse analysis, resulting in
      three categories: meanings attributed to tuberculosis and health needs and care
      characteristics. The conceptions regarding the disease are supported by the multi
      causal theory of the health-disease process. The care is characterized by
      interventions that go beyond the biological dimension. The precarious living
      conditions define the needs of most people with tuberculosis, and can be more
      important to the ill than the very diagnosis of the disease, influencing
      treatment adherence, and should gain relevance in care.

PMID- 22481721
TI  - Relationship among social support, treatment adherence and metabolic control of
      diabetes mellitus patients.
AB  - This cross-sectional and quantitative study aimed to analyze the relationship
      among social support, adherence to non-pharmacological (diet and physical
      exercise) and pharmacological treatments (insulin and/or oral anti-diabetic
      medication) and clinical and metabolic control of 162 type 2 diabetes mellitus
      patients. Data were collected through instruments validated for Brazil. Social
      support was directly correlated with treatment adherence. Adherence to non
      pharmacological treatment was inversely correlated with body mass index, and
      medication adherence was inversely correlated with diastolic blood pressure.
      There were no associations between social support and clinical and metabolic
      control variables. Findings indicate that social support can be useful to achieve
      treatment adherence. Studies with other designs should be developed to broaden
      the analysis of relations between social support and other variables.

PMID- 22481722
TI  - Effectiveness of participatory-action-research to put in practice evidence at a
      nursing onco-hematology unit.
AB  - The aim was to evaluate the effectiveness of evidence implementation through
      participatory-action research (PAR). A prospective quasi-experimental design with
      two non-equivalent and non-concurrent groups (2006 and 2008) was adopted. The
      research was conducted at the bone marrow transplant unit of a tertiary-level
      Spanish hospital. To put the evidence in practice, PAR was adopted as an
      "intervention studied". The dependent variables were: professional performance
      and patient outcomes (psycho-emotional area and adverse effects). In total, 125
      patients were recruited (1(st) period=56; 2(nd) period=69). The results in the
      second period show significant improvements in professional performance in terms
      of the quality of the registers of signs and symptoms. In the psycho-emotional
      area, the psycho-social adjustment improved significantly; without caregiver
      burden or satisfaction showing any clear tendencies. Among the adverse effects,
      catheter-related thrombosis and catheter-related infection improved
      significantly; there were no significant differences in the level of pain or
      mucositis. Through the PAR, evidence could be put in practice and the outcomes
      under analysis could be improved.

PMID- 22481723
TI  - Patients' experiences of peritoneal dialysis at home: a phenomenological
      approach.
AB  - The aim of this study was to highlight the meaning of home dialysis as
      experienced by patients with chronic renal failure. The research design was
      influenced by Ricoeur's phenomenology. Nineteen patients from a Brazilian public
      hospital were interviewed, from May to September 2009. Interviews were guided by
      the question: "Tell me about your experiences lived undergoing PD". Findings
      unveiled the patients' perception of the drastic changes in their existence,
      consequent to disease and treatment; and the perception of themselves in that
      process. The feeling of anguish, physical pain and deprivations were part of
      living that condition. They foresee an uncertain future, depending on the
      expertise of health care providers and the demands on support of significant
      others. Findings suggest that individual aspects of patients' experiences must be
      considered if health care providers are to facilitate positive health outcomes.

PMID- 22481724
TI  - The Pain Disability Questionnaire: a reliability and validity study.
AB  - The goal of this study was to translate and adapt The Pain Disability
      Questionnaire (PDQ) to Brazilian Portuguese, as well as to assess its
      psychometric properties and practicability. The following methodological steps
      were followed: translation, synthesis, back-translation, expert committee
      assessment and pre-test. The psychometric properties were assessed through the
      application of a questionnaire to 119 patients with chronic musculoskeletal
      disorders. The results indicated the reliability of the instrument, with a
      Cronbach's alpha coefficient of 0.86, and high stability in the test-retest. A
      moderate correlation was found between the PDQ scores and the numerical pain
      scale. Negative correlations were found between the Spitzer Quality of Life Index
      and the functional condition, psychosocial component and total PDQ score.
      Construct validity demonstrated significant difference in PDQ scores between
      symptomatic and asymptomatic individuals. The PDQ revealed fast application and
      easy understanding. The results indicated a successful cultural adaptation and
      reliable psychometric properties.

PMID- 22481725
TI  - Functional disability of adult individuals with spinal cord injury and its
      association with socio-demographic characteristics.
AB  - The aim was to investigate the Functional Disability degree in adults with spinal
      cord injury and its association with socio-demographic characteristics. The
      Barthel Index was used and 75 subjects answered a questionnaire with socio
      demographic variables. The Chi-Square, Cronbach's Alpha and Fisher tests were
      used in the analysis. The mean age was 42.23 years. Cronbach's Alpha for the
      Barthel Index was 0.807. The activities that were more difficult to perform were
      Climbing and Descending Stairs (92%) and Walking (82.7%). The mean Barthel Index
      score was 64 points. The tests of association demonstrated values with p>0.05.
      Even though this population demonstrated a low degree of dependency and no
      association was identified between the socio-demographic variables and Functional
      Disability, the study contributes to nursing care for individuals with spinal
      cord injury, considering the limitations the condition imposes on their self
      care.

PMID- 22481726
TI  - Associations among socio-demographic and clinical factors and the quality of life
      of ostomized patients.
AB  - This study identifies the socio-demographic and clinical factors of patients with
      irreversible colostomy secondary to colorectal cancer and correlates them with
      quality of life (QOL). It is a cross-sectional study. Socio-demographic and
      clinical data were collected through interviews and the WHOQOL-bref to assess
      QOL. The sample comprised 60 patients. Most of the patients were male, elderly
      individuals, half were married and half did not have a sexual partner, with
      complete primary education, receiving up to two times the minimum wage, carried a
      stoma for three months on average, were instructed they would carry a stoma, but
      did not have their stoma marked prior to surgery. The average QOL score was
      75.500, while the psychological, social and physical domains were the most
      affected. No statistically significant differences were found in QOL in relation
      to the following socio-demographic and clinical factors: female gender, low
      income, no sexual partners, and lack of instruction. The patients with an
      intestinal stoma presented a satisfactory QOL.

PMID- 22481727
TI  - Process of construction of an educational booklet for health promotion of
      pregnant women.
AB  - This study aimed to describe the production process of an educational booklet
      focusing on health promotion of pregnant women. The action research method was
      used in this process composed of the following steps: choice of the content based
      on the needs of pregnant women, creation of illustrations, content preparation
      based on scientific literature, validation of the material by experts and
      pregnant women. This work resulted in the final version of the booklet, which was
      entitled "Celebrating life: our commitment with the health promotion of pregnant
      women". Active participation of health professionals and pregnant women through
      dialogue and collective strategy permeated the process of development of the
      booklet. The opinions of pregnant women and experts who considered the booklet
      enriching and enlightening justify the use of it as an additional resource of
      educational activities carried out during the prenatal care.

PMID- 22481728
TI  - Impact of a participatory program to reduce noise in a neonatal unit.
AB  - This study evaluated the impact of a participatory program to reduce noise in a
      neonatal intermediate care unit of a university hospital. A time-series quasi
      experimental design was used, in which sound pressure levels were measured before
      and after the intervention was implemented using the Quest-400 dosimeter. Non
      parametric statistical tests were used to compare noise with the level of
      significance fixed at 5%. Results showed significant reduction of sound pressure
      levels in the neonatal unit after the intervention program was implemented
      (p<0.0001). The average Leq before the intervention was 62.5dBA and was reduced
      to 58.8dBA after the intervention. A reduction of 7.1dBA in the average Lmax(from
      104.8 to 87.7dBA) and of 30.6dBA in the average Lpeak(from 138.1 to 107.5dBA) was
      observed. The program was proven to be effective in significantly reducing noise
      levels in the neonatal unit, although levels were still more intense than
      recommended.

PMID- 22481729
TI  - Children with Type 1 Diabetes Mellitus and their friends: the influence of this
      interaction in the management of the disease.
AB  - Friends' support is a key element in the management of Type 1 Diabetes Mellitus.
      This study describes the influence of friends on the lives of children with
      Diabetes Mellitus and its implications for managing the disease. Empirical data
      were collected through semi-structured interviews, supported with the use of
      puppets, with 19 children aged between seven and 12 years old. The qualitative
      analysis of the testimonies allowed understanding the phenomenon from two
      perspectives: the attitude of friends towards the child, positively or negatively
      affecting the disease's management, and the attitude of the child toward friends.
      The knowledge of those involved and the interaction between the children with DM1
      and their friends impacts the management of the disease. Understanding the
      implications of these interactions contributes to the delivery of qualified
      nursing care to this population.

PMID- 22481730
TI  - The dialogic life-death in care delivery to adolescents with cancer.
AB  - This study aims to understand the experience of adolescents with cancer, family
      and the health team regarding death in the healthcare context, in the light of
      Edgar Morin's proposed theoretical framework of complexity. Participants were 12
      adolescents, 14 relatives and 25 health professionals. The interview was used for
      data collection. The discussion of data was guided by the dialogic life-death in
      the context of care to adolescents with cancer. It was observed that the
      singularity in the way the adolescent experiences time and faces death and the
      possibility that the family will lose a loved one may not be in accordance with
      the care the health team offers, considering structural, organizational and
      affective aspects. It is not enough for the team just to rationally make choices
      on the use of diagnostic-therapeutic devices, in line with predefined moments in
      the disease. Instead, a contextualized and sensitive understanding of each
      situation is needed.

PMID- 22481731
TI  - Hospitalization of children under five years of age due to avoidable causes.
AB  - This study characterizes the profile of hospital morbidity according to the main
      diagnosis upon admission, in individuals younger than five years old, residents
      of three cities (Maringa, Sarandi and Paicandu) in the Parana state, Brazil.
      Information contained in hospital admission forms from 1998 to 2009 was used. The
      hospitalizations of 41,220 individuals younger than five years old were analyzed.
      The results indicate a decline of 16.1% in hospital admissions of patients
      younger than five years old in relation to the total number of admissions in all
      age groups. As for the main diagnoses, there were diseases of the respiratory
      system (55.6%), infectious and parasitic diseases (14.8%) and diseases
      originating in the perinatal period (12.9%). Such conditions can be avoided by
      implementing primary health care measures, which shows the need to intensify the
      actions recommended by the programs directed to child health.

PMID- 22481732
TI  - Critical incidents of trust erosion in leadership of head nurses.
AB  - Investigations show that distrust towards head figures has a particularly
      negative effect on organizational dynamics. Because of this, the main types of
      behavior associated with distrust in nursing professionals with leadership duties
      have been identified, examining which aspect of reliability is most frequently
      related to distrust. Based on an analysis of 61 critical incidents, selected from
      90 hospital employees, the most frequently mentioned behavior types related to
      distrust were "Public Abuse", "Not giving permission for time off for a special
      occasion" and especially an erosion of trustworthiness in the leader's integrity
      dimension. The implications of these findings are discussed, so that nursing
      professionals can avoid the development of distrust in interpersonal
      relationships and damage to the appropriate functioning of health services.

PMID- 22481733
TI  - Nursing in the hospital accreditation process: practice and implications in the
      work quotidian.
AB  - The aim of this study was to investigate the role and influence of nursing in the
      hospital accreditation process. It is a qualitative study, conducted in a private
      hospital of Belo Horizonte. The study subjects were nine nurses and 15 nursing
      technicians. Data collection was through semi-structured interviews, which were
      subjected to content analysis. The results showed that the role of the nursing
      team in the accreditation involves care, administrative, educational and research
      issues. The study subjects presented different perceptions regarding the
      influence of the accreditation process in their work. The positive aspects of
      personal growth and valorization of the curriculum were highlighted as well as
      negative aspects such as stress and little professional valorization. Therefore,
      it is necessary that the professionals understand the logic of the process and
      act with a view to the interdisciplinarity and overcoming the fragmentation of
      care, thus achieving integral healthcare and the quality of care desired.

PMID- 22481734
TI  - Presenteeism in hospital nurses.
AB  - This quantitative, descriptive, cross-sectional research aimed to determine the
      estimated productivity of health-related limitations at work in 129 nurses
      working in direct care delivery to critical and potentially critical patients.
      Instruments were applied for socio-demographic and functional characterization
      and for the evaluation of presenteeism (Work Limitations Questionnaire).
      Statistical Package for the Social Sciences software was used for data analysis.
      In this study, 75% of nurses obtained a lost productivity index of up to 4.84%.
      The physical demand domain represented the major limitation for these
      professionals (25%). Presenteeism was directly correlated to health care,
      occurrence and number of absences, and indirectly related to work time at the
      unit. It was concluded that organizational or individual factors influence
      individuals' productivity, in view of the circumstances involving care delivery
      to critical and potentially critical patients.

PMID- 22481735
TI  - Quality of life and depressive symptoms among caregivers and drug dependent
      people.
AB  - The aim of this study was to evaluate the quality of life and the presence of
      depressive symptoms among the caregivers and drug dependent people of the CAPSad.
      This is a cross-sectional study, with 109 users of four Psychosocial Care Centers
      for alcohol and other drugs of Mato Grosso and their caregivers, using the
      instruments: Medical Outcomes Studies 36 (SF-36), Beck Depression Inventory (BDI)
      and a sociodemographic variables questionnaire. The QoL of the caregivers in the
      domains functional capacity, physical aspect, pain and vitality were more
      affected when compared to the users. A strong correlation between QoL and
      depressive symptoms was found in both groups. The comparisons performed
      demonstrate a compromise in the quality of life of both, with the group of
      caregivers most affected, confirming the situation of drug dependence as an
      important factor in the perception of the caregiver regarding their quality of
      life.

PMID- 22481736
TI  - Minor psychiatric disorders among nurses university faculties.
AB  - This cross-sectional study addresses 130 nursing faculty members in federal
      universities from Rio Grande do Sul, Brazil. It investigated the psychological
      demands and decision latitude (the Demand-Control Model by Karasek) and their
      association with Minor Psychological Disorders (MPDs). The Brazilian versions of
      the Self-Report-Questionnaire-20 and the Job Stress Scale were used. MPDs were
      prevalent in 20% of the studied individuals. After adjusting for potential
      confounders, the chances of participants presenting mental disorders were higher
      in the quadrant 'active strain jobs' (OR=14.23, 95% CI 1.55 to 130.73), followed
      by the 'high strain jobs' quadrant (OR=10.05, 95% CI 1.23 to 82.44), compared to
      nursing professors classified in the 'low strain jobs' quadrant. We conclude that
      high psychological demands and low control over work can cause disorders in
      nursing professors, among them, MPDs.

PMID- 22481737
TI  - Active cutaneous warming systems to prevent intraoperative hypothermia: a
      systematic review.
AB  - This study analyzed the evidence available in the literature concerning the
      effectiveness of different active cutaneous warming systems to prevent
      intraoperative hypothermia. This is a systematic review with primary studies
      found in the following databases: CINAHL, EMBASE, Cochrane Register of Controlled
      Trials and Medline. The sample comprised 23 randomized controlled trials. There
      is evidence in the literature indicating that the circulating water garment
      system is the most effective in maintaining patient body temperature. These
      results can support nurses in the decision-making process concerning the
      implementation of effective measures to maintain normothermia, though the
      decision of health services concerning which system to choose should also take
      into account its cost-benefit status given the cost related to the acquisition of
      such systems.

PMID- 22481738
TI  - Professional competences of nurse to work in Intensive Care Units: an integrative
      review.
AB  - This study aimed to identify and analyze nurses' competences to work at Intensive
      Care Units-ICU. An integrative review method was used, and data were collected in
      LILACS, SciELO and BDENF, from August to October 2010. Ten articles were
      identified, published in the last 12 years. Data grouping permitted the
      construction of thematic units related to nurses' competences: nursing care
      management, high-complexity nursing care delivery, decision making, leadership,
      communication, continuing/permanent education, human resource management,
      material resource management. The professional competences identified can support
      the outline of guidelines to constitute the profile of nursing working in
      intensive care units and drive/mobilize the improvement of nursing care
      practices.

PMID- 22481739
TI  - Infant mortality and prenatal care: contributions of the clinic in the light of
      Canguilhem and Foucault.
AB  - This review study aimed to verify how studies conducted in Brazil have related
      infant mortality to prenatal care and to present contributions of the clinic in
      the light of Canguilhem and Foucault for qualification of the care. An
      integrative literature review was conducted from searches in the databases
      SciELO, LILACS, MEDLINE and BDENF for the period 2000 to 2009. The relationship
      between infant mortality and prenatal care is related to the insufficient number
      of consultations or to the quality of the care provided. Even when the number of
      and routine consultations in the prenatal care were adequate, avoidable deaths
      were present. For the qualification of prenatal care, it is suggested that the
      clinical knowledge and other elements that comprise the process of human living
      are considered, in order that the clinical view is enlarged and articulated to
      the technologies available in the health system and, together, they are able to
      contribute to the reduction of infant mortality in Brazil.

PMID- 22481740
TI  - A humble man in tireless pursuit: Shu Chien, a 2010 national medal of science
      awardee.
AB  - On his 70th birthday, Shu Chien's colleagues put together a 600-page book of
      letters, essays, and photographs as a tribute not only to his contributions to
      the field of bioengineering but also in honor of his character as a valued
      friend, research collaborator, and family member. Perhaps they thought that the
      book would commemorate the moment when Chien began to consider retirement. But in
      the last decade, he has added more than 140 publications to an already impressive
      list of 379. And he shows no sign of slowing down.

PMID- 22481741
TI  - Ultrasound? Fetal monitoring? Spectrometer? There's an app for that!: biomedical
      smart phone apps are taking healthcare by storm.
AB  - If you think your doctor is a mobile phone junkie now, you haven't seen anything
      yet. A profusion of new software applications, or apps, are either already here
      or coming soon to convert smart phones into biomedical devices that will play a
      larger role in healthcare. Engineers, computer programmers, medical
      professionals, and other researchers are jumping on the bandwagon to create apps
      and add-on devices, or peripherals, that turn a smart phone into a microscope, an
      ultrasound machine, or a heart-rate monitor, just to name a few.

PMID- 22481742
TI  - Measuring driver impairments: sleepiness, distraction, and workload.
AB  - Snow was falling heavily when Sarah was driving on a slippery road to her
      cousin's country cottage. It was dark outside, and the visibility was poor. She
      had planned to arrive before sunset, but the rental service had made a mistake,
      and it took hours before she got her rental car at the airport. It was past
      midnight now, and after a long day of traveling, Sarah was starting to get
      sleepy. Fortunately, there were only 15 km to go, but her eyelids were starting
      to feel heavy. To stay awake, she put her favorite CD on, turned up the volume,
      and started to sing along. This seemed to help a little-good-only 10 km to go.
      This was when Sarah's phone started ringing, and she awkwardly tried to find the
      mute button for the car stereo while answering the phone. As she looked up again,
      she barely caught a glimpse of the red brake lights of the car in front of her as
      she smashed into it.

PMID- 22481743
TI  - Brain enabled by next-generation neurotechnology: using multiscale and multimodal
      models.
AB  - As many articles in this issue of IEEE Pulse demonstrate, interfacing directly
      with the brain presents several fundamental challenges. These challenges reside
      at multiple levels and span many disciplines, ranging from the need to understand
      brain states at the level of neural circuits to creating technological
      innovations to facilitate new therapeutic options. The goal of our
      multiuniversity research team, composed of researchers from Stanford University,
      Brown University, the University of California at San Francisco (UCSF), and the
      University College London (UCL), is to substantially elevate the fundamental
      understanding of brain information processing and its relationship with
      sensation, behavior, and injury. Our team was assembled to provide expertise
      ranging from neuroscience to neuroengineering and to neurological and psychiatric
      clinical guidance, all of which are critical to the overarching research goal. By
      employing a suite of innovative experimental, computational, and theoretical
      approaches, the Defense Advanced Research Projects Agency (DARPA) Reorganization
      and Plasticity to Accelerate Injury Recovery (REPAIR) team has set its sights on
      learning how the brain and its microcircuitry react (e.g., to sudden
      physiological changes) and what can be done to encourage recovery from such
      (reversible) injury. In this article, we summarize some of the team's technical
      goals, approaches, and early illustrative results.

PMID- 22481744
TI  - FDA regulation of invasive neural recording electrodes: a daunting task for
      medical innovators.
AB  - The U.S. Food and Drug Administration (FDA) is charged with assuring the safety
      and effectiveness of medical devices. Before any medical device can be brought to
      market, it must comply with all federal regulations regarding FDA processes for
      clearance or approval. Navigating the FDA regulatory process may seem like a
      daunting task to the innovator of a novel medical device who has little
      experience with the FDA regulatory process or device commercialization. This
      review introduces the basics of the FDA regulatory premarket process, with a
      focus on issues relating to chronically implanted recording devices in the
      central or peripheral nervous system. Topics of device classification and
      regulatory pathways, the use of standards and guidance documents, and optimal
      time lines for interaction with the FDA are discussed. Additionally, this article
      summarizes the regulatory research on neural implant safety and reliability
      conducted by the FDA's Office of Science and Engineering Laboratories (OSEL) in
      collaboration with Defense Advanced Research Projects Agency (DARPA) Reliable
      Neural Technology (RE-NET) Program. For a more detailed explanation of the
      medical device regulatory process, please refer to several excellent reviews of
      the FDA's regulatory pathways for medical devices [1]-[4].

PMID- 22481745
TI  - Magnetic resonance connectome automated pipeline: an overview.
AB  - This article presents a novel, tightly integrated pipeline for estimating a
      connectome. The pipeline utilizes magnetic resonance (MR) imaging (MRI) data to
      produce a high-level estimate of the structural connectivity in the human brain.
      The MR connectome automated pipeline (MRCAP) is efficient, and its modular
      construction allows researchers to modify algorithms to meet their specific
      requirements. The pipeline has been validated, and more than 200 connectomes have
      been processed and analyzed to date.

PMID- 22481746
TI  - Intracranial pressure signal morphology: real-time tracking.
AB  - The waveform morphology of intracranial pressure (ICP) pulses holds essential
      information about intracranial and cerebrovascular pathophysiologies. Automatic
      analysis of the ICP waveforms may help to predict abnormal increase of ICP and
      thus prevent severe complications in patients treated for traumatic brain
      injuries (TBIs). This article describes a probabilistic framework to track the
      ICP waveform morphology in real time. The model represents the correlation
      between different ICP morphological metrics extracted within a single pulse as
      well as the temporal dependence of metrics extracted between successive pulses.
      Morphological tracking is solved using Bayesian inference in a dynamic graphical
      model that associates a random variable to each morphological metric.

PMID- 22481747
TI  - Real-time unconstrained object recognition: a processing pipeline based on the
      mammalian visual system.
AB  - The mammalian visual system is still the gold standard for recognition accuracy,
      flexibility, efficiency, and speed. Ongoing advances in our understanding of
      function and mechanisms in the visual system can now be leveraged to pursue the
      design of computer vision architectures that will revolutionize the state of the
      art in computer vision.

PMID- 22481748
TI  - Neural interfaces for upper-limb prosthesis control: opportunities to improve
      long-term reliability.
AB  - Building on a long history of innovation in neural-recording interfaces, the
      Defense Advanced Research Projects Agency (DARPA) has launched a program to
      address the key challenges related to transitioning advanced neuroprosthesis
      technology to clinical use for amputated service members. The goal of the
      Reliable Neural Technology (RE-NET) Program is to develop new technology to
      extract information from the nervous system at a scale and rate needed to
      reliably control modern robotic prostheses over the lifetime of the amputee. The
      RE-NET program currently encompasses three separate efforts: histology for
      interface stability over time (HIST), reliable peripheral interfaces (RPIs), and
      reliable central nervous system (CNS) interfaces (RCIs).

PMID- 22481749
TI  - Natural and accelerated recovery from brain damage: experimental and theoretical
      approaches.
AB  - The goal of the Caltech group is to gain insight into the processes that occur
      within the primate nervous system during dexterous reaching and grasping and to
      see whether natural recovery from local brain damage can be accelerated by
      artificial means. We will create computational models of the nervous system
      embodying this insight and explain a variety of clinically observed neurological
      deficits in human subjects using these models.

PMID- 22481750
TI  - The modern hospital in historical context: a modern health bonanza
      [retrospectroscope].
AB  - The evolution and development of hospitals in their historical context are
      quickly reviewed in this column, starting first as simple shelters for the sick
      and indigent who were waiting essentially for death, and up to the relatively
      recent concept of true health centers where patients face a high probability of
      actual recovery and rehabilitation. Anesthesia, microbiology, asepsia,
      antibiotics, virology, radiology, transfusion, and different biomedical
      engineering technologies, as well as knowledge in other basic sciences, have led
      to the intensive care and emergency units that were introduced in the 1960s,
      which lead to the specialty of critical care medicine and positioning the patient
      as the center of care. These brief words anticipate what we develop below.

PMID- 22481751
TI  - Twenty-first century: the beginning of the replacement parts era?

PMID- 22481752
TI  - Red blood cell transfusions worsen the outcomes even in critically ill patients
      undergoing a restrictive transfusion strategy.
AB  - CONTEXT AND OBJECTIVE: Anemia and blood transfusions are common in intensive
      care. This study aimed to evaluate epidemiology and outcomes among critically ill
      patients under a restrictive transfusion strategy. DESIGN AND SETTING:
      Prospective observational cohort study in an intensive care unit (ICU) at a
      tertiary hospital. METHODS: All adults admitted to the ICU over a one-year period
      who remained there for more than 72 hours were included, except those with acute
      coronary syndrome, ischemic stroke, acute hemorrhage, prior transfusion, pregnant
      women and Jehovah's Witnesses. The restrictive strategy consisted of transfusion
      indicated when hemoglobin levels were less than or equal to 7.0 g/dl. RESULTS:
      The study enrolled 167 patients; the acute physiology and chronic health
      evaluation II (APACHE II) score was 28.9 +/- 6.5. The baseline hemoglobin level
      was 10.6 +/- 2.2 g/dl and on day 28, it was 8.2 +/- 1.3 g/dl (P < 0.001).
      Transfusions were administered to 35% of the patients. In the transfusion group,
      61.1% did not survive, versus 48.6% in the non-transfusion group (P = 0.03).
      Transfusion was an independent risk factor for mortality (P = 0.011; odds ratio,
      OR = 2.67; 95% confidence interval, CI = 1.25 to 5.69). ICU stay and hospital
      stay were longer in the transfusion group: 20.0 (3.0-83.0) versus 8.0 (3.0-63.0)
      days (P < 0,001); and 24.0 (3.0-140.0) versus 14.0 (3.0-80.0) days (P = 0.002),
      respectively. CONCLUSIONS: In critically ill patients, there was a reduction in
      hemoglobin with increasing length of ICU stay. Moreover, transfusion was
      associated with worse prognoses.

PMID- 22481753
TI  - Prevalence of common mental disorders in mothers in the semiarid region of
      Alagoas and its relationship with nutritional status.
AB  - CONTEXT AND OBJECTIVE: Compromised maternal mental health (MMH) is considered to
      be a risk factor for child malnutrition in low income areas. Psychosocial
      variables associated with MMH are potentially different between urban and rural
      environments. The aim here was to investigate whether associations existed
      between MMH and selected sociodemographic risk factors and whether specific to
      urban or rural settings. DESIGN AND SETTING: Cross-sectional study on a
      representative population sample of mothers from the semiarid region of Alagoas.
      METHODS: Multistage sampling was used. The subjects were mothers of children aged
      up to 60 months. MMH was evaluated through the Self-Reporting Questionnaire-20.
      Mothers' nutritional status was assessed using the body mass index and waist
      circumference. Univariate analysis used odds ratios (OR) and chi-square. Logistic
      regression was performed separately for urban and rural subsamples using MMH as
      the dependent variable. RESULTS: The sample comprised 288 mothers. The
      prevalences of common mental disorders (CMD) in rural and urban areas were 56.2%
      and 43.8%, respectively (OR = 1.03; 95% CI: 0.64-1.63). In univariate analysis
      and logistic regression, the variable of education remained associated with MMH
      (OR = 2.2; 95% CI: 1.03-4.6) in urban areas. In rural areas, the variable of lack
      of partner remained associated (OR = 2.6; 95% CI: 1.01-6.7). CONCLUSIONS: The
      prevalence of CMD is high among mothers of children aged up to two years in the
      semiarid region of Alagoas. This seems to be associated with lower educational
      level in urban settings and lack of partner in rural settings.

PMID- 22481754
TI  - Number of fragments, margin status and thermal artifacts of conized specimens
      from LLETZ surgery to treat cervical intraepithelial neoplasia.
AB  - CONTEXT AND OBJECTIVE: Large loop excision of the transformation zone (LLETZ) is
      a nontraumatic cut and coagulation method with several advantages, but it induces
      thermal artifacts in the cut region. The aim here was to assess the correlations
      of age, number of fragments, lesion grade and degree of thermal artifacts with
      margin quality in conized specimens from LLETZ for cervical intraepithelial
      neoplasia (CIN). DESIGN AND SETTING: Cross-sectional study at Universidade
      Federal de Sao Paulo (Unifesp). METHODS: The records and histopathology findings
      of 118 women who underwent LLETZ between 1999 and 2007 were reviewed. Age, number
      of fragments, lesion grade, degree of thermal artifacts and margin quality were
      assessed. RESULTS: The patients' mean age was 27.14 years; 63.6% had been
      diagnosed with CIN II and 36.4% with CIN III. The lesion was removed as a single
      fragment in 79.6% of the cases. The margins were free from intraepithelial
      neoplasia in 85.6% and compromised in the endocervical margin in 6.8%. Fragment
      damage due to artifacts occurred in 2.5%. Severe artifacts occurred in 22.8%.
      Women aged 30 years or over presented more cases of CIN III (P < 0.0004).
      Neoplastic compromising of surgical margins and severe artifacts occurred more
      often in cases in which two or more fragments were removed, and in patients aged
      30 years or over. CONCLUSION: CIN III in women aged 30 or over, when removed in
      two or more fragments during LLETZ, presented a greater number of compromised
      margins and greater severity of thermal artifacts.

PMID- 22481755
TI  - Correlation between balance and the level of functional independence among
      elderly people.
AB  - CONTEXT AND OBJECTIVE: As the overall number of elderly people increases there is
      a corresponding rise in the number of older persons with disabilities. In order
      to examine whether there is any relationship between balance and activities of
      daily living, we evaluated balance and daily activities among elderly people
      living in the community. DESIGN AND SETTING: Cross-sectional study at
      Universidade Estadual Paulista (Unesp), Marilia, Sao Paulo, Brazil. METHODS: The
      study included 70 community-dwelling elderly people aged 65 and over. Balance was
      evaluated using the Berg Balance Scale (BBS) and physical independence in daily
      activities was evaluated using the Barthel Index (BI). The Spearman correlation
      coefficient was used to examine the relationship between the parameters
      evaluated. Significance was set at the level of 5% (P < 0.05). RESULTS: The
      population's mean age was 70.5 +/- 5 years. The mean BBS score was 50.9 +/- 4.1,
      whereas the mean BI score was 98.1 +/- 2.8. Statistically significant
      relationships were found between the BBS and BI (r = 0.41; P = 0.0004); between
      age and BI (r = -0.24; P = 0.04); and between age and BBS (r = -0.57; P =
      0.0001). CONCLUSIONS: The results showed that among elderly people, there are
      correlations between age, balance and independence level.

PMID- 22481756
TI  - Relationship between lower-limb muscle strength and frailty among elderly people.
AB  - CONTEXT AND OBJECTIVE: Sarcopenia is the main factor involved in the development
      of frailty syndrome. The aims here were to investigate relationships between
      lower-limb muscle strength and the variables of sex, age and frailty criteria;
      compare lower-limb muscle strength with each frailty criterion; and assess the
      power of each criterion for estimating the risk of frailty among elderly
      outpatients. DESIGN AND SETTING: Cross-sectional study at the Geriatrics
      Outpatient Clinic of a university hospital in Campinas. METHOD: A non
      probabilistic convenience sample of 150 elderly people of both sexes who were
      followed up as outpatients was assessed. Sociodemographic data (sex and age) and
      physical health data (frailty criteria and the five-times sit-to-stand test) were
      gathered. Descriptive, comparative and multivariate logistic regression analyses
      were performed. RESULTS: The majority of the elderly people (77.3%) were 70 years
      of age or over, with predominance of females (64.2%) and had a low score for the
      five-times sit-to-stand test (81.4% scored 0 or 1); 55.3% of the elderly people
      presented three or more frailty criteria. A significant association was found
      between lower-limb muscle strength and the variables of age and number of frailty
      criteria. CONCLUSIONS: Lower levels of lower-limb muscle strength were associated
      with advanced age and greater presence of signs of frailty. Moreover, lower-limb
      muscle strength was also associated with the criteria of reduced walking speed
      criteria and hand-grip strength.

PMID- 22481757
TI  - Use of epidemiological data as the basis for developing a medical curriculum.
AB  - CONTEXT AND OBJECTIVE: Epidemiology may help educators to face the challenge of
      establishing content guidelines for the curricula in medical schools. The aim was
      to develop learning objectives for a medical curriculum from an epidemiology
      database. DESIGN AND SETTING: Descriptive study assessing morbidity and mortality
      data, conducted in a private university in Sao Paulo. METHODS: An epidemiology
      database was used, with mortality and morbidity recorded as summaries of deaths
      and the World Health Organization's Disability-Adjusted Life Year (DALY). The
      scoring took into consideration probabilities for mortality and morbidity.
      RESULTS: The scoring presented a classification of health conditions to be used
      by a curriculum design committee, taking into consideration its highest and
      lowest quartiles, which corresponded respectively to the highest and lowest
      impact on morbidity and mortality. Data from three countries were used for
      international comparison and showed distinct results. The resulting scores
      indicated topics to be developed through educational taxonomy. CONCLUSION: The
      frequencies of the health conditions and their statistical treatment made it
      possible to identify topics that should be fully developed within medical
      education. The classification also suggested limits between topics that should be
      developed in depth, including knowledge and development of skills and attitudes,
      regarding topics that can be concisely presented at the level of knowledge.

PMID- 22481758
TI  - Description of color/race in Brazilian biomedical research.
AB  - CONTEXT AND OBJECTIVE: Over recent years, the terms race and ethnicity have been
      used to ascertain inequities in public health. However, this use depends on the
      quality of the data available. This study aimed to investigate the description of
      color/race in Brazilian scientific journals within the field of biomedicine.
      DESIGN AND SETTING: Descriptive study with systematic search for scientific
      articles in the SciELO Brazil database. METHODS: A wide-ranging systematic search
      for original articles involving humans, published in 32 Brazilian biomedical
      scientific journals in the SciELO Brazil database between January and December
      2008, was performed. Articles in which the race/ethnicity of the participants was
      identified were analyzed. RESULTS: In total, 1,180 articles were analyzed. The
      terms for describing race or ethnicity were often ambiguous and vague.
      Descriptions of race or ethnicity occurred in 159 articles (13.4%), but only in
      42 (26.4%) was there a description of how individuals were identified. In these,
      race and ethnicity were used almost interchangeably and definition was according
      to skin color (71.4%), ancestry (19.0%) and self-definition (9.6%). Twenty-two
      races or ethnicities were cited, and the most common were white (37.3%), black
      (19.7%), mixed (12.9%), nonwhite (8.1%) and yellow (8.1%). CONCLUSION: The
      absence of descriptions of parameters for defining race, as well as the use of
      vague and ambiguous terms, may hamper and even prevent comparisons between human
      groups and the use of these data to ascertain inequities in healthcare.

PMID- 22481759
TI  - Risk of persistent high-grade squamous intraepithelial lesion after
      electrosurgical excisional treatment with positive margins: a meta-analysis.
AB  - CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly
      treated, there is a risk of persistence or recurrence. The aim here was to
      quantify the risks of persistence of high-grade intraepithelial squamous lesions,
      one and two years after cervical electrosurgical excisional treatment with
      positive margins. DESIGN AND SETTING: Systematic review of the literature and
      meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on
      studies published between January 1989 and July 2009 that were identified in
      Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho,
      Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they
      were cohort studies on electrosurgical excisional treatment of high-grade
      squamous intraepithelial lesions with a minimum follow-up of one year, a
      histopathological outcome of persistence of these lesions and a small risk of
      bias. RESULTS: The search identified 7,066 articles and another 21 in the
      reference lists of these papers. After applying the selection and exclusion
      criteria, only four articles were found to have extractable data. The risk of
      persistence of high-grade intraepithelial lesions after one year was 11.36 times
      greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with
      positive margins and after two years, was four times greater (95% CI: 0.996
      16.164), although without statistical significance. CONCLUSION: This meta
      analysis confirms the importance of positive margins as an indicator of
      incomplete treatment after the first year of follow-up and highlights the need
      for appropriately chosen electrosurgical techniques based on disease location and
      extent, with close surveillance of these patients.

PMID- 22481760
TI  - Mucosa-associated lymphoid tissue lymphoma of the trachea: case report.
AB  - CONTEXT: Mucosa-associated lymphoid tissue (MALT) lymphomas are most commonly
      found in the stomach, lungs, orbital soft tissue, salivary glands and thyroid.
      Involvement of the trachea is extremely rare. CASE REPORT: This report describes
      a rare case of MALT lymphoma of the trachea in a 71-year-old woman who presented
      with a one-year history of coughing, dyspnea, hoarseness and weight loss. There
      was an infiltrative lesion in the mid-trachea. The anatomopathological diagnosis
      was only made from the fifth endoscopic biopsy attempt. Immunochemotherapy
      consisting of rituximab, cyclophosphamide, vincristine and prednisone (R-COP)
      induced complete remission of the symptoms and endoscopic lesion. CONCLUSIONS:
      MALT lymphoma of the trachea is extremely rare and indolent disease. It has to be
      considered in the differential diagnosis of airway lesions. It is crucial to
      obtain an anatomopathological diagnosis from a specialized pathologist.
      Immunochemotherapy with R-COP induced complete remission of the disease.

PMID- 22481761
TI  - Determination of lactate value.

PMID- 22481763
TI  - Psychosocial interventions for premature ejaculation.

PMID- 22481764
TI  - Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children
      and adults.

PMID- 22481765
TI  - Introduction to the special issue on the 2011 Joint IEEE International Frequency
      Control Symposium and European Frequency and Time Forum.
AB  - The 8 invited and 17 contributed papers in this special issue focus on the
      following topical areas covered at the 2011 Joint IEEE International Frequency
      Control Symposium and European Frequency and Time Forum, held in San Francisco,
      California: 1) Materials and Resonators; 2) Oscillators, Synthesizers, and Noise;
      3) Microwave Frequency Standards; 4) Sensors and Transducers; 5) Timekeeping and
      Time and Frequency Transfer; and 6) Optical Frequency Standards.

PMID- 22481766
TI  - Positioning FBAR technology in the frequency and timing domain.
AB  - This paper focuses on the technical differentiation of film bulk acoustic
      resonator (FBAR) technology from other mechanical resonator technologies for
      timing applications. The paper will touch on a recent modification of FBARs, the
      zero-drift resonator (ZDR), that is temperature compensated. One technology
      differentiator is the size of the chip-scale packaged resonator. Another is that
      the silicon lid is perfectly suitable for placement of integrated circuits and
      this is currently being done. Many factors (wide tuning range, high Q, high
      frequency, small size, integrated circuitry) are being used to differentiate
      potential products for the time and frequency markets.

PMID- 22481767
TI  - Mechanically coupled CMOS-MEMS free-free beam resonator arrays with enhanced
      power handling capability.
AB  - Integrated CMOS-MEMS free-free beam resonator arrays operated in a standard two
      port electrical configuration with low motional impedance and high power handling
      capability, centered at 10.5 MHz, have been demonstrated using the combination of
      pull-in gap reduction mechanism and mechanically coupled array design. The
      mechanical links (i.e., coupling elements) using short stubs connect each
      constituent resonator of an array to its adjacent ones at the high-velocity
      vibrating locations to accentuate the desired mode and reject all other spurious
      modes. A single second-mode free-free beam resonator with quality factor Q > 2200
      and motional impedance R(m) < 150 kOmega has been used to achieve mechanically
      coupled resonator arrays in this work. In array design, a 9-resonator array has
      been experimentally characterized to have performance improvement of
      approximately 10* on motional impedance and power handling as compared with that
      of a single resonator. In addition, the two-port electrical configuration is much
      preferred over a one-port configuration because of its low-feedthrough and high
      design flexibility for future oscillator and filter implementation.

PMID- 22481768
TI  - Electrostatically tunable piezoelectric-on-silicon micromechanical resonator for
      real-time clock.
AB  - This paper reports on the design, fabrication, and characterization of a small
      form factor, piezoelectrically transduced, tunable micromechanical resonator for
      real-time clock (RTC) applications (32.768 kHz). The device was designed to
      resonate in an out-of-plane flexural mode to simultaneously achieve low-frequency
      operation and reduced motional resistance in a small die area. Finite element
      simulations were extensively used to optimize the structure in terms of size,
      insertion loss, spurious-mode rejection, and frequency tuning. Microresonators
      with an overall die area of only 350 * 350 MUm were implemented on a thin-film
      AlN on silicon-on-insulator (SOI) substrate with AlN thickness of 0.5 MUm, device
      layer of 1.5 MUm, and an electrostatic tuning gap size of 1 MUm. A frequency
      tuning range of 3100 ppm was measured using dc voltages of less than 4 V. This
      range is sufficient to compensate for frequency variations of the microresonator
      across temperature from -20 degrees C to 100 degrees C. The device exhibits low
      motional impedance that is completely independent of the frequency tuning
      potential. Discrete electronics were used in conjunction with the resonator to
      implement an oscillator, verifying its functionality as a timing reference.

PMID- 22481769
TI  - High-acoustic-impedance tantalum oxide layers for insulating acoustic reflectors.
AB  - This work describes the assessment of the acoustic properties of sputtered
      tantalum oxide films intended for use as high-impedance films of acoustic
      reflectors for solidly mounted resonators operating in the gigahertz frequency
      range. The films are grown by sputtering a metallic tantalum target under
      different oxygen and argon gas mixtures, total pressures, pulsed dc powers, and
      substrate biases. The structural properties of the films are assessed through
      infrared absorption spectroscopy and X-ray diffraction measurements. Their
      acoustic impedance is assessed by deriving the mass density from X-ray
      reflectometry measurements and the acoustic velocity from picosecond acoustic
      spectroscopy and the analysis of the frequency response of the test resonators.

PMID- 22481770
TI  - Modeling phase noise in multifunction subassemblies.
AB  - Obtaining requisite phase noise performance in hardware containing multifunction
      circuitry requires accurate modeling of the phase noise characteristics of each
      signal path component, including both absolute (oscillator) and residual (non
      oscillator) circuit contributors. This includes prediction of both static and
      vibration-induced phase noise. The model (usually in spreadsheet form) is refined
      as critical components are received and evaluated. Additive (KTBF) phase noise
      data can be reasonably estimated, based on device drive level and noise figure.
      However, accurate determination of component near-carrier (multiplicative) and
      vibration-induced noise usually must be determined via measurement. The model
      should also include the effects of noise introduced by IC voltage regulators and
      properly discriminate between common versus independent signal path residual
      noise contributors. The modeling can be easily implemented using a spreadsheet.

PMID- 22481771
TI  - Simplified phase noise model for negative-resistance oscillators and a comparison
      with feedback oscillator models.
AB  - This paper describes a greatly simplified model for the prediction of phase noise
      in oscillators which use a negative resistance as the active element. It is based
      on a simple circuit consisting of the parallel addition of a noise current, a
      negative admittance/resistance, and a parallel (Qlimited) resonant circuit. The
      transfer function is calculated as a forward trans-resistance (VOUT/IIN) and then
      converted to power. The effect of limiting is incorporated by assuming that the
      phase noise element of the noise floor is kT/2, i.e., -177 dBm/Hz at room
      temperature. The result is the same as more complex analyses, but enables a
      simple, clear insight into the operation of oscillators. The phase noise for a
      given power in the resonator appears to be lower than in feedback oscillators.
      The reasons for this are explained. Simulation and experimental results are
      included.

PMID- 22481772
TI  - Progress in atomic fountains at LNE-SYRTE.
AB  - We give an overview of the work done with the Laboratoire National de Metrologie
      et d'Essais-Systemes de Reference Temps-Espace (LNE-SYRTE) fountain ensemble
      during the last five years. After a description of the clock ensemble, comprising
      three fountains, FO1, FO2, and FOM, and the newest developments, we review recent
      studies of several systematic frequency shifts. This includes the distributed
      cavity phase shift, which we evaluate for the FO1 and FOM fountains, applying the
      techniques of our recent work on FO2. We also report calculations of the
      microwave lensing frequency shift for the three fountains, review the status of
      the blackbody radiation shift, and summarize recent experimental work to control
      microwave leakage and spurious phase perturbations. We give current accuracy
      budgets. We also describe several applications in time and frequency metrology:
      fountain comparisons, calibrations of the international atomic time, secondary
      representation of the SI second based on the (87)Rb hyperfine frequency, absolute
      measurements of optical frequencies, tests of the T2L2 satellite laser link, and
      review fundamental physics applications of the LNE-SYRTE fountain ensemble.
      Finally, we give a summary of the tests of the PHARAO cold atom space clock
      performed using the FOM transportable fountain.

PMID- 22481773
TI  - Observation and cancellation of a perturbing dc stark shift in strontium optical
      lattice clocks.
AB  - We report on the observation of a dc Stark frequency shift at the 10-(13) level
      by comparing two strontium optical lattice clocks. This frequency shift arises
      from the presence of electric charges trapped on dielectric surfaces placed under
      vacuum close to the atomic sample. We show that these charges can be eliminated
      by shining UV light on the dielectric surfaces, and characterize the residual dc
      Stark frequency shift on the clock transition at the 10-(18) level by applying an
      external electric field. This study shows that the dc Stark shift can play an
      important role in the accuracy budget of lattice clocks, and should be duly taken
      into account.

PMID- 22481774
TI  - Operating a (87)Sr optical lattice clock with high precision and at high density.
AB  - We describe recent experimental progress with the JILA Sr optical frequency
      standard, which has a systematic uncertainty at the 10-(16) fractional frequency
      level. An upgraded laser system has recently been constructed in our lab which
      may allow the JILA Sr standard to reach the standard quantum measurement limit
      and achieve record levels of stability. To take full advantage of these
      improvements, it will be necessary to operate a lattice clock with a large number
      of atoms, and systematic frequency shifts resulting from atomic interactions will
      become increasingly important. We discuss how collisional frequency shifts can
      arise in an optical lattice clock employing fermionic atoms and describe a novel
      method by which such systematic effects can be suppressed.

PMID- 22481775
TI  - Realization of an ultrastable 578-nm laser for an Yb lattice clock.
AB  - In this paper, we describe the development of an ultrastable laser source at 578
      nm, realized using frequency sum generation. This source will be used to excite
      the clock transition (1)S(0) - (3)P(0) in an ytterbium optical lattice clock
      experiment. Two independent ultrastable lasers have been realized, and the laser
      frequency noise and stability have been characterized.

PMID- 22481776
TI  - Characterizing a fiber-based frequency comb with electro-optic modulator.
AB  - We report on the characterization of a commercial- core fiber-based frequency
      comb equipped with an intracavity free-space electro-optic modulator (EOM). We
      investigate the relationship between the noise of the pump diode and the laser
      relative intensity noise (RIN) and demonstrate the use of a low-noise current
      supply to substantially reduce the laser RIN. By measuring several critical
      transfer functions, we evaluate the potential of the EOM for comb repetition rate
      stabilization. We also evaluate the coupling to other relevant parameters of the
      comb. From these measurements, we infer the capabilities of the femtosecond laser
      comb to generate very-low-phase-noise microwave signals when phase-locked to a
      high-spectral-purity ultra-stable laser.

PMID- 22481777
TI  - Blackbody radiation shifts in optical atomic clocks.
AB  - A review of recent theoretical calculations of blackbody radiation (BBR) shifts
      in optical atomic clocks is presented. We summarize previous results for
      monovalent ions that were obtained by a relativistic all-order single-double
      method, where all single and double excitations of the Dirac- Fock wave function
      are included to all orders of perturbation theory. A recently developed method
      for accurate calculations of BBR shifts in divalent atoms is then presented. This
      approach combines the relativistic all-order method and the configuration
      interaction method, which provides for accurate treatment of correlation
      corrections in atoms with two valence electrons. Calculations of the BBR shifts
      in B+, Al+, and In+ have enabled us to reduce the present fractional
      uncertainties in the frequencies of their clock transitions as measured at room
      temperature: to 4 * 10-19 for Al+ and 10-18 for B+ and In+. These uncertainties
      approach recent estimates of the limits of precision of currently proposed
      optical atomic clocks. We discuss directions of future theoretical developments
      for reducing clock uncertainties resulting from blackbody radiation shifts.

PMID- 22481778
TI  - Microfabricated chip-scale rubidium plasma light source for miniature atomic
      clocks.
AB  - We present the microfabrication and characterization of a low-power, chip-scale
      Rb plasma light source, designed for optical pumping in miniature atomic clocks.
      A dielectric barrier discharge (DBD) configuration is used to ignite a Rb plasma
      in a micro-fabricated Rb vapor cell on which external indium electrodes were
      deposited. The device is electrically driven at frequencies between 1 and 36 MHz,
      and emits 140 MUW of stable optical power while coupling less than 6 mW of
      electrical power to the discharge cell. Optical powers of up to 15 and 9 MUW are
      emitted on the Rb D2 and D1 lines, respectively. Continuous operation of the
      light source for several weeks has been demonstrated, showing its capacity to
      maintain stable optical excitation of Rb atoms in chip-scale double-resonance
      atomic clocks.

PMID- 22481779
TI  - Pulsed optically pumped rubidium clock with high frequency-stability performance.
AB  - In this paper, we present the performance of a vapor-cell rubidium frequency
      standard working in the pulsed regime, in which the clock signal is represented
      by a Ramsey pattern observed on an optically detected laser absorption signal.
      The main experimental results agree with previously reported theoretical
      predictions. In particular, we measured a relative frequency stability of
      sigmay(tau) - 1.6 * 10(-13)tau-1/2 for integration times, tau, up to 200 s, which
      represents a record in short-term stability for a vapor-cell clock. We also
      discuss the most important physical phenomena that contribute to this result.

PMID- 22481780
TI  - Liquid sensor utilizing a regular phononic crystal with normal incidence of
      sound.
AB  - A phononic crystal device is investigated as sensor platform utilizing resonant
      transmission. Here, we use a phononic crystal plate consisting of a solid matrix
      and liquidfilled holes. The device is fully immersed into the liquid in such a
      way that the incidence direction of sound is normal to the plate. A
      characteristic transmission peak, calculated using finite-difference time-domain
      (FDTD) and determined with two different experimental setups, has been found to
      strongly depend on the liquid sound velocity. The peak maximum frequency serves
      as measure for liquid composition.

PMID- 22481781
TI  - In situ observation and measurement of the SAW thin-film acoustoelectric effect.
AB  - The thin-film acoustoelectric effect in SAW devices describes the interaction of
      electrical energy between a SAW in a piezoelectric medium and a thin film in the
      wave's propagation path. The real-time observation of the thin-film
      acoustoelectric interaction is useful in the design and characterization of SAW
      sensors (i.e., temperature, humidity, viscosity, voltage, current, Hall effects,
      etc.). An in situ test fixture was designed to be mechanically, thermally, and
      electrically stable. Data acquisition software and an electron beam evaporation
      system were configured for real-time thin-film characterization during film
      growth. Data have been observed for more than 20 SAW devices and over a wide
      range of frequencies (i.e., 62 MHz to 1 GHz). The results suggest that the use of
      the in situ procedure yielded good agreement between theoretical predictions and
      the measured data, which demonstrates a method for the characterization of a SAW
      H(2)-gas sensor in real-time.

PMID- 22481782
TI  - Theoretical and experimental studies of a surface acoustic wave flow sensor.
AB  - A novel SAW flow sensor is proposed based on pressure measurement. The
      relationship between the flow rate and the pressure difference along the flow
      path is evaluated. The results show a linear relationship between the flow rate
      and pressure difference, which agrees with the past research results. Strain
      analysis and FEM simulation show that phase delay depends linearly on the flow
      rate passing the SAW sensor, whereas SAW frequency decreases linearly upon the
      increase of flow rate. Phase delay experiment results agree with analysis and
      simulation, and the frequency change falls in a reasonable range around the
      predicted curve.

PMID- 22481783
TI  - A review of reduced Kalman filters for clock ensembles.
AB  - This paper reviews the author's previous work on free-running timescales based on
      Kalman filters that act upon clock comparisons. The natural Kalman clock ensemble
      algorithm tends to optimize long-term timescale stability at the expense of short
      term stability. By subjecting each postmeasurement error covariance matrix to a
      non-transparent reduction operation, one obtains corrected clocks with improved
      short-term stability and little sacrifice of long-term stability. A new result on
      covariance matrix reduction is also stated.

PMID- 22481784
TI  - Space-based augmentation for global navigation satellite systems.
AB  - This paper describes space-based augmentation for global navigation satellite
      systems (GNSS). Space-based augmentations increase the accuracy and integrity of
      the GNSS, thereby enhancing users' safety. The corrections for ephemeris,
      ionospheric delay, and clocks are calculated from reference station measurements
      of GNSS data in wide-area master stations and broadcast via geostationary earth
      orbit (GEO) satellites. This paper discusses the clock models, satellite orbit
      determination, ionospheric delay estimation, multipath mitigation, and GEO uplink
      subsystem (GUS) as used in the Wide Area Augmentation System developed by the
      FAA.

PMID- 22481785
TI  - Detection of atomic clock frequency jumps with the Kalman filter.
AB  - Frequency jumps are common anomalies in atomic clocks aboard navigation system
      satellites. These anomalous behaviors must be detected quickly and accurately to
      minimize the impact on user positioning. We develop a detector for frequency
      jumps based on the Kalman filter. Numerical simulations show that the detector is
      fast, with high probability of detection and low probability of false alarms. It
      also has a low computational cost because it takes advantage of the recursive
      nature of the Kalman filter. Therefore, it can be used in applications in which
      little computational power is available, such as aboard navigation system
      satellites.

PMID- 22481786
TI  - A wavelet-based multiscale ensemble time-scale algorithm.
AB  - The wide-spread availability of ensembles of high-performance clocks has
      motivated interest in time-scale algorithms. There are many such algorithms in
      use today in applications ranging from scientific to commercial. Although these
      algorithms differ in key aspects and are sometimes tailored for specific
      applications and mixtures of clocks, they all share the goal of combining
      measured time differences between clocks to form a reference time scale that is
      more stable than any of the clocks in the ensemble. A new approach to forming
      time scales is presented here, the multiscale ensemble timescale (METS)
      algorithm. This approach is based on a multiresolution analysis afforded by the
      discrete wavelet transform. The algorithm does not assume a specific parametric
      model for the clocks involved and hence is well-suited for an ensemble of highly
      disparate clocks. The approach is based on an appealing optimality criterion
      which yields a reference time scale that is more stable than the constituent
      clocks over all averaging intervals (scales). The METS algorithm is presented
      here in detail and is shown in a simulation study to compare favorably with a
      time-scale algorithm based on Kalman filtering.

PMID- 22481787
TI  - Statistical biases and very-long-term time stability analysis.
AB  - The prediction of very-long-term time stability is a key issue in various fields,
      such as time keeping, obviously, but also navigation and spatial applications.
      This is usually performed by extrapolating the measurement data obtained by
      estimators such as the Allan variance, modified Allan variance, Hadamard
      variance, etc. This extrapolation may be assessed from a fit over the variance
      estimates. However, this fit should be performed on the log-log graph of the
      estimates, which corresponds to a least-squares minimization of the relative
      difference between the variance estimates and the fitting curve. However, a bias
      exists between the average of the log of the estimates and the log of the true
      value of the estimated variance. This paper presents the theoretical calculation
      of this log-log bias based on the number of equivalent degrees of freedom of the
      estimates, shows simulations over a large number of realizations, and provides a
      reliable method of unbiased logarithmic fit. Extrapolating this fit yields a more
      confident assessment of the very-long-term time stability.

PMID- 22481788
TI  - First international two-way satellite time and frequency transfer experiment
      employing dual pseudo-random noise codes.
AB  - Two-way satellite time and frequency transfer (TWSTFT) is one of the main
      techniques used to compare atomic time scales over long distances. To both
      improve the precision of TWSTFT and decrease the satellite link fee, a new
      software-defined modem with dual pseudo-random noise (DPN) codes has been
      developed. In this paper, we demonstrate the first international DPN-based TWSTFT
      experiment over a period of 6 months. The results of DPN exhibit excellent
      performance, which is competitive with the Global Positioning System (GPS)
      precise point positioning (PPP) technique in the short-term and consistent with
      the conventional TWSTFT in the long-term. Time deviations of less than 75 ps are
      achieved for averaging times from 1 s to 1 d. Moreover, the DPN data has less
      diurnal variation than that of the conventional TWSTFT. Because the DPN-based
      system has advantages of higher precision and lower bandwidth cost, it is one of
      the most promising methods to improve international time-transfer links.

PMID- 22481789
TI  - Improvement of the Asia-Pacific TWSTFT network solutions by using DPN results.
AB  - Two major time and frequency transfer techniques, two-way satellite time and
      frequency transfer (TWSTFT) and global navigation satellite systems (GNSS: GPS,
      GALILEO, GLONASS, etc.), are used for the generation of Coordinated Universal
      Time (UTC)/International Atomic Time (TAI). These time and frequency transfer
      links comprise a worldwide network and the utilization of the highly redundant
      time and frequency data is an important topic. Two methods, either TW-only
      network (i.e., TWSTFT) or single-link combination of TW and Global Positioning
      System (GPS), have been developed for combining the redundant data from different
      techniques. In our previous study, we have proposed a feasible method, utilizing
      full time-transfer network data, to improve the results of TWSTFT network. The
      National Institute of Information and Communications Technology (NICT) has
      recently developed a software-based two-way time-transfer modem using a dual
      pseudo-random noise (DPN) signal. The first international DPN TWSTFT experiment,
      using these modems, was performed between NICT (Japan) and Telecommunication
      Laboratories (TL; Taiwan)and its ability to improve the time transfer precision
      was demonstrated. In comparison with the conventional NICT-TLTWSTFT link, the DPN
      time transfer results have higher precision and lower diurnal effects. The
      estimation also shows that DPN is comparable to GPS precise point positioning
      (PPP).Because the DPN results show better performance than the conventional
      TWSTFT results, we would adopt the DPN data for the NICT-TL link and solve the
      TW+DPN network solutions by using our proposed method. The concept of this
      application is similar to the so-called multi-technique-network time/frequency
      transfer. The encouraging results confirm that the TWSTFT network performance can
      benefit from DPN data by improving short-term stabilities and reducing diurnal
      effects.The results of TW+PPP network solutions are also illustrated.

PMID- 22481790
TI  - Near real-time comparison and monitoring of time scales with precise point
      positioning using NRCan ultra-rapid products.
AB  - This paper experimentally evaluates the assessment of precise point positioning
      (PPP) using the Natural Resources Canada (NRCan) Ultra-Rapid GPS products to
      serve as a short latency time-transfer tool to assist timing laboratories in
      operational maintenance of frequency standards and time scale dissemination. An
      automated data exchange and processing system has been set up to serve the
      international community for efficient, nearly real-time clock comparison and
      monitoring purposes.

PMID- 22481791
TI  - Reversibility of electric-field-induced mechanical changes in soft tissues.
AB  - Recently, ultrasound has been used to study the physiological-level electric
      field-induced mechanical changes (EIMC) in general soft biological tissues. Here,
      we present the experimental results on the dependence of EIMC on the polarity of
      the applied electric field. We applied an ac voltage source to heart tissues and
      monitored the amplitude changes and time shifting of the ultrasound echoes. The
      shifting of the echoes was decomposed into a trend component and a fluctuation
      (feature) component. The changes in amplitude and the fluctuation component of
      the time shift, but not the trend component of the time shift, can be mostly
      reversed by reversing the polarity of the applied voltage. The polarity
      dependence study reveals two different mechanisms underlying EIMC.

PMID- 22481792
TI  - Measurement of evanescent wave properties of a bulk acoustic wave resonator.
AB  - Acoustic wave fields in a thin-film bulk acoustic wave resonator are studied
      using a heterodyne laser interferometer. The measurement area is extended outside
      the active electrode region of the resonator, so that wave fields in both the
      active and surrounding regions can be characterized. At frequencies at which the
      region surrounding the resonator does not support laterally propagating acoustic
      waves, the analysis of the measurement data shows exponentially decaying
      amplitude fields outside the active resonator area, as suggested by theory. The
      magnitude of the imaginary wave vectors is determined by fitting an exponential
      function to the measured amplitude data, and thereby the experimentally
      determined dispersion diagram is extended into the region of imaginary wave
      numbers.

PMID- 22481793
TI  - A substrate integrated folded waveguide (SIFW) H-plane band-pass filter with
      double H-plane septa based on LTCC.
AB  - In this paper, a novel substrate integrated folded waveguide (SIFW) H-plane band
      pass filter based on low-temperature co-fired ceramic technology (LTCC) is
      proposed which employs double H-plane septa of a short-ended evanescent waveguide
      as an impedance inverter. The filter has advantages of convenient integration,
      compact, low cost, mass-producibility, and ease of fabrication, and it also has
      frequency responses similar to those of traditional E-plane double-iris waveguide
      band-pass filters. To validate the new proposed topology, a three-pole narrowband
      band-pass filter is designed and fabricated using half-wavelength resonators. A
      comparison between measured results and simulated results shows good agreement.

PMID- 22481794
TI  - Voltage-controlled narrowband and wide, variable-range four-segment quartz
      crystal oscillator.
AB  - In this work, our goal is to develop a voltage-controlled variable-frequency
      quartz crystal oscillator with narrowband response, wide, variable frequency
      range and the capacity to oscillate across the series resonance frequency using a
      four-segment configuration of a quartz crystal oscillator. In conventional quartz
      oscillators, the quartz resonator is inserted in the feedback loop between the
      input and the output of the active circuit, providing sufficient gain and the
      phase relation. In the oscillator developed here, the quartz crystal resonator is
      inserted between the loop circuit and the ground potential. The performance of
      the voltage-controlled variable-frequency oscillator is demonstrated across the
      series resonance frequency.

PMID- 22481795
TI  - Compounded direct pixel beamforming for medical ultrasound imaging.
AB  - In this paper, a new compounded direct pixel beamforming (CDPB) method is
      presented to remove blurring artifacts introduced by ultrasound scan conversion.
      In CDPB, receive focusing is directly performed on each display pixel in
      Cartesian coordinates using the raw RF data from adjacent transmit firings so
      that artifacts from the scan conversion can be removed. In addition, the energy
      variations resulting from the distance between the transmit scanline and display
      pixel are compensated by utilizing the gain factor obtained from the ultrasound
      beam pattern. The proposed CDPB method was evaluated using simulation and in vivo
      liver data acquired by a commercial ultrasound machine equipped with a research
      package. The experimental results showed that the proposed CDPB method improved
      the information entropy contrast (IEC) by 23.6% compared with the conventional
      scan conversion method and it reduced the blocking artifacts factor (BAF) by
      16.4% over the direct pixel-based focusing method. These results indicate the
      proposed new direct pixel beamforming method could be used to enhance image
      quality in medical ultrasound imaging.

PMID- 22481796
TI  - Real-time scan assistant for echocardiography.
AB  - A real-time scan assistant (SA) for use with echocardiography is presented. The
      motivation is to aid nonexpert users in capturing apical 4-chamber views (A4CH)
      during echocardiography. The algorithm is based on a parametric multi-chamber
      model of the A4CH view, updated in an extended Kalman filter framework. The
      regional model goodness-of-fit is used to calculate a score, which is provided to
      the user during acquisition, together with an icon (emoticon) indicating whether
      the current view is acceptable or not. The SA was implemented on a commercially
      available scanner. A feasibility test was performed using two healthy volunteers
      as models and 10 medical students acting as nonexpert users. The students
      examined the models on two occasions, separated more than four days in time. Half
      of the students used the SA during the first exam and no SA at the second exam.
      The other half used the opposite order. The recordings were later rated by a
      cardiologist. A Wilcoxon signed pair rank test revealed a statistically
      significant improvement when using SA. Nine cases were rated as poor without
      using the SA. In eight (89%) of these cases, view quality improved to acceptable
      when the SA was used.

PMID- 22481797
TI  - A singular-value method for reconstruction of nonradial and lossy objects.
AB  - Efficient inverse scattering algorithms for nonradial lossy objects are presented
      using singular-value decomposition to form reduced-rank representations of the
      scattering operator. These algorithms extend eigenfunction methods that are not
      applicable to nonradial lossy scattering objects because the scattering operators
      for these objects do not have orthonormal eigenfunction decompositions. A method
      of local reconstruction by segregation of scattering contributions from different
      local regions is also presented. Scattering from each region is isolated by
      forming a reduced-rank representation of the scattering operator that has domain
      and range spaces comprised of far-field patterns with retransmitted fields that
      focus on the local region. Methods for the estimation of the boundary, average
      sound speed, and average attenuation slope of the scattering object are also
      given. These methods yielded approximations of scattering objects that were
      sufficiently accurate to allow residual variations to be reconstructed in a
      single iteration. Calculated scattering from a lossy elliptical object with a
      random background, internal features, and white noise is used to evaluate the
      proposed methods. Local reconstruction yielded images with spatial resolution
      that is finer than a half wavelength of the center frequency and reproduces sound
      speed and attenuation slope with relative root-mean-square errors of 1.09% and
      11.45%, respectively.

PMID- 22481799
TI  - Enhancing the accuracy of subcutaneous glucose sensors: a real-time deconvolution
      based approach.
AB  - Minimally invasive continuous glucose monitoring (CGM) sensors can greatly help
      diabetes management. Most of these sensors consist of a needle electrode, placed
      in the subcutaneous tissue, which measures an electrical current exploiting the
      glucose-oxidase principle. This current is then transformed to glucose levels
      after calibrating the sensor on the basis of one, or more, self-monitoring blood
      glucose (SMBG) samples. In this study, we design and test a real-time signal
      enhancement module that, cascaded to the CGM device, improves the quality of its
      output by a proper postprocessing of the CGM signal. In fact, CGM sensors measure
      glucose in the interstitium rather than in the blood compartment. We show that
      this distortion can be compensated by means of a regularized deconvolution
      procedure relying on a linear regression model that can be updated whenever a
      pair of suitably sampled SMBG references is collected. Tests performed both on
      simulated and real data demonstrate a significant accuracy improvement of the CGM
      signal. Simulation studies also demonstrate the robustness of the method against
      departures from nominal conditions, such as temporal misplacement of the SMBG
      samples and uncertainty in the blood-to-interstitium glucose kinetic model.
      Thanks to its online capabilities, the proposed signal-enhancement algorithm can
      be used to improve the performance of CGM-based real-time systems such as the
      hypo/hyper glycemic alert generators or the artificial pancreas.

PMID- 22481800
TI  - Surface mosaics of the bladder reconstructed from endoscopic video for automated
      surveillance.
AB  - Flexible cystoscopy is frequently performed for recurrent bladder cancer
      surveillance, making it the most expensive cancer to treat over the patient's
      lifetime. An automated bladder surveillance system is being developed to
      robotically scan the bladder surface using an ultrathin and highly flexible
      endoscope. Such a system would allow cystoscopic procedures to be overseen by
      technical staff while urologists could review cystoscopic video postoperatively.
      In this paper, we demonstrate a method for reconstructing the surface of the
      whole bladder from endoscopic video using structure from motion. Video is
      acquired from a custom ultrathin and highly flexible endoscope that can retroflex
      to image the entire internal surface of the bladder. Selected frames are
      subsequently stitched into a mosaic and mapped to a reconstructed surface,
      creating a 3-D surface model of the bladder that can be expediently reviewed. Our
      software was tested on endoscopic video of an excised pig bladder. The resulting
      reconstruction possessed a projection error of 1.66 pixels on average and covered
      99.6% of the bladder surface area.

PMID- 22481801
TI  - Multilevel segmentation of histopathological images using cooccurrence of tissue
      objects.
AB  - This paper presents a new approach for unsupervised segmentation of
      histopathological tissue images. This approach has two main contributions. First,
      it introduces a new set of high-level texture features to represent the prior
      knowledge of spatial organization of the tissue components. These texture
      features are defined on the tissue components, which are approximately
      represented by tissue objects, and quantify the frequency of two component types
      being cooccurred in a particular spatial relationship. As they are defined on
      components, rather than on image pixels, these object cooccurrence features are
      expected to be less vulnerable to noise and variations that are typically
      observed at the pixel level of tissue images. Second, it proposes to obtain
      multiple segmentations by multilevel partitioning of a graph constructed on the
      tissue objects and combine them by an ensemble function. This multilevel graph
      partitioning algorithm introduces randomization in graph construction and
      refinements in its multilevel scheme to increase diversity of individual
      segmentations, and thus, improve the final result. The experiments on 200 colon
      tissue images reveal that the proposed approach--the object cooccurrence features
      together with the multilevel segmentation algorithm--is effective to obtain high
      quality results. The experiments also show that it improves the segmentation
      results compared to the previous approaches.

PMID- 22481802
TI  - Real-time automatic tuning of noise suppression algorithms for cochlear implant
      applications.
AB  - The performance of cochlear implants deteriorates in noisy environments compared
      to quiet conditions. This paper presents an adaptive cochlear implant system,
      which is capable of classifying the background noise environment in real time for
      the purpose of adjusting or tuning its noise suppression algorithm to that
      environment. The tuning is done automatically with no user intervention. Five
      objective quality measures are used to show the superiority of this adaptive
      system compared to a conventional fixed noise-suppression system. Steps taken to
      achieve the real-time implementation of the entire system, incorporating both the
      cochlear implant speech processing and the background noise suppression, on a
      portable PDA research platform are presented along with the timing results.

PMID- 22481803
TI  - Augmented dynamics and motor exploration as training for stroke.
AB  - With chronic stroke survivors (n = 30), we investigated how upper extremity
      training with negative viscosity affects coordination under unperturbed
      conditions. Subjects trained with a planar robotic interface simulating 1)
      negative viscosity augmented to elbow and shoulder joints; 2) negative viscosity
      combined with inertia; or 3) a null-field condition. Two treatment groups
      practiced with both force conditions (cross-over design), while a control group
      practiced with a null-field condition. Training (exploratory movement) and
      evaluations (prescribed circular movement) alternated in several phases to
      facilitate transfer from forces to the null field. Negative viscosity expanded
      exploration especially in the sagittal axis, and resulted in significant within
      day improvements. Both treatment groups exhibited next day retention unobserved
      in the control. Our results suggest enhanced learning from forces that induce a
      broader range of kinematics. This study supports the use of robot-assisted
      training that encourages active patient involvement by preserving efferent
      commands for driving movement.

PMID- 22481804
TI  - Generating stochastic gene regulatory networks consistent with pathway
      information and steady-state behavior.
AB  - We present a procedure to generate a stochastic genetic regulatory network model
      consistent with pathway information. Using the stochastic dynamics of Markov
      chains, we produce a model constrained by the prior knowledge despite the
      sometimes incomplete, time independent, and often conflicting nature of these
      pathways. We apply the Markov theory to study the model's long run behavior and
      introduce a biologically important transformation to aid in comparison with real
      biological outcome prediction in the steady-state domain. Our technique produces
      biologically faithful models without the need for rate kinetics, detailed timing
      information, or complex inference procedures. To demonstrate the method, we
      produce a model using 28 pathways from the biological literature pertaining to
      the transcription factor family nuclear factor-kappaB. Predictions from this
      model in the steady-state domain are then validated against nine mice knockout
      experiments.

PMID- 22481805
TI  - Biopsy needle artifact localization in MRI-guided robotic transrectal prostate
      intervention.
AB  - Recently a number of robotic intervention systems for magnetic resonance image
      (MRI)-guided needle placement in the prostate have been reported. In MRI-guided
      needle interventions, after a needle is inserted, the needle position is often
      confirmed with a volumetric MRI scan. Commonly used titanium needles are not
      directly visible in an MRI, but they generate a susceptibility artifact in the
      immediate neighborhood of the needle. This paper reports the results of a
      quantitative study of the relationship between the true position of titanium
      biopsy needle and the corresponding needle artifact position in MRI, thereby
      providing a better understanding of the influence of needle artifact on targeting
      errors. The titanium needle tip artifact extended 9 mm beyond the actual needle
      tip location with tendency to bend toward the scanner's B  (0) magnetic field
      direction, and axially displaced 0.38 and 0.32 mm (mean) in scanner's frequency
      and phase encoding direction, respectively.

PMID- 22481807
TI  - Modeling individual human motor behavior through model reference iterative
      learning control.
AB  - A computational model is proposed in this paper to capture learning capacity of a
      human subject adapting his or her movements in novel dynamics. The model uses an
      iterative learning control algorithm to represent human learning through
      repetitive processes. The control law performs adaptation using a model designed
      using experimental data captured from the natural behavior of the individual of
      interest. The control signals are used by a model of the body to produced motion
      without the need of inverse kinematics. The resulting motion behavior is
      validated against experimental data. This new technique yields the capability of
      subject-specific modeling of the motor function, with the potential to explain
      individual behavior in physical rehabilitation.

PMID- 22481806
TI  - Image reconstruction for hybrid true-color micro-CT.
AB  - X-ray micro-CT is an important imaging tool for biomedical researchers. Our group
      has recently proposed a hybrid "true-color" micro-CT system to improve contrast
      resolution with lower system cost and radiation dose. The system incorporates an
      energy-resolved photon-counting true-color detector into a conventional micro-CT
      configuration, and can be used for material decomposition. In this paper, we
      demonstrate an interior color-CT image reconstruction algorithm developed for
      this hybrid true-color micro-CT system. A compressive sensing-based statistical
      interior tomography method is employed to reconstruct each channel in the local
      spectral imaging chain, where the reconstructed global gray-scale image from the
      conventional imaging chain served as the initial guess. Principal component
      analysis was used to map the spectral reconstructions into the color space. The
      proposed algorithm was evaluated by numerical simulations, physical phantom
      experiments, and animal studies. The results confirm the merits of the proposed
      algorithm, and demonstrate the feasibility of the hybrid true-color micro-CT
      system. Additionally, a "color diffusion" phenomenon was observed whereby high
      quality true-color images are produced not only inside the region of interest,
      but also in neighboring regions. It appears harnessing that this phenomenon could
      potentially reduce the color detector size for a given ROI, further reducing
      system cost and radiation dose.

PMID- 22481808
TI  - A class of Monte-Carlo-based statistical algorithms for efficient detection of
      repolarization alternans.
AB  - Cardiac repolarization alternans is an electrophysiologic condition identified by
      a beat-to-beat fluctuation in action potential waveform. It has been
      mechanistically linked to instances of T-wave alternans, a clinically defined ECG
      alternation in T-wave morphology, and associated with the onset of cardiac
      reentry and sudden cardiac death. Many alternans detection algorithms have been
      proposed in the past, but the majority have been designed specifically for use
      with T-wave alternans. Action potential duration (APD) signals obtained from
      experiments (especially those derived from optical mapping) possess unique
      characteristics, which requires the development and use of a more appropriate
      alternans detection method. In this paper, we present a new class of algorithms,
      based on the Monte Carlo method, for the detection and quantitative measurement
      of alternans. Specifically, we derive a set of algorithms (one an analytical and
      more efficient version of the other) and compare its performance with the
      standard spectral method and the generalized likelihood ratio test algorithm
      using synthetic APD sequences and optical mapping data obtained from an alternans
      control experiment. We demonstrate the benefits of the new algorithm in the
      presence of Gaussian and Laplacian noise and frame-shift errors. The proposed
      algorithms are well suited for experimental applications, and furthermore, have
      low complexity and are implementable using fixed-point arithmetic, enabling
      potential use with implantable cardiac devices.

PMID- 22481810
TI  - An ensemble-based system for microaneurysm detection and diabetic retinopathy
      grading.
AB  - Reliable microaneurysm detection in digital fundus images is still an open issue
      in medical image processing. We propose an ensemble-based framework to improve
      microaneurysm detection. Unlike the well-known approach of considering the output
      of multiple classifiers, we propose a combination of internal components of
      microaneurysm detectors, namely preprocessing methods and candidate extractors.
      We have evaluated our approach for microaneurysm detection in an online
      competition, where this algorithm is currently ranked as first, and also on two
      other databases. Since microaneurysm detection is decisive in diabetic
      retinopathy (DR) grading, we also tested the proposed method for this task on the
      publicly available Messidor database, where a promising AUC 0.90  +/- 0.01 is
      achieved in a "DR/non-DR"-type classification based on the presence or absence of
      the microaneurysms.

PMID- 22481809
TI  - Modular closed-loop control of diabetes.
AB  - Modularity plays a key role in many engineering systems, allowing for plug-and
      play integration of components, enhancing flexibility and adaptability, and
      facilitating standardization. In the control of diabetes, i.e., the so-called
      "artificial pancreas," modularity allows for the step-wise introduction of (and
      regulatory approval for) algorithmic components, starting with subsystems for
      assured patient safety and followed by higher layer components that serve to
      modify the patient's basal rate in real time. In this paper, we introduce a three
      layer modular architecture for the control of diabetes, consisting in a
      sensor/pump interface module (IM), a continuous safety module (CSM), and a real
      time control module (RTCM), which separates the functions of insulin
      recommendation (postmeal insulin for mitigating hyperglycemia) and safety
      (prevention of hypoglycemia). In addition, we provide details of instances of all
      three layers of the architecture: the APS(c) serving as the IM, the safety
      supervision module (SSM) serving as the CSM, and the range correction module
      (RCM) serving as the RTCM. We evaluate the performance of the integrated system
      via in silico preclinical trials, demonstrating 1) the ability of the SSM to
      reduce the incidence of hypoglycemia under nonideal operating conditions and 2)
      the ability of the RCM to reduce glycemic variability.

PMID- 22481811
TI  - Viscoelastic modeling of the contact interaction between a tactile sensor and an
      atrial tissue.
AB  - Modeling and parameter identification of soft tissue are essential in
      establishing an accurate contact model for tool-tissue interaction, which can be
      used in the development of high-fidelity surgical instruments. This paper
      discusses the interaction between a tissue and a tactile sensor in minimally
      invasive surgery, the focus being a novel technique for robotic-assisted mitral
      valve repair, in which tactile sensors are used to distinguish between different
      kinds of tissue by their relative softness. A discrete viscoelastic model is
      selected to represent the tissue behavior. To populate the model of the tissue
      with actual data, a set of tissue-testing experiments is designed and implemented
      on the atrial tissue of a swine heart by analyzing its dynamic response. By means
      of a genetic algorithm, data of the complex compliance are extracted and used to
      find the coefficients of the model. Further, a viscoelastic contact model is
      developed to model the interaction between the tissue and the tactile sensor with
      annular shape. Finally, the relation among the indentation displacement, the
      ratio of the radii, and the applied force is established parametrically.

PMID- 22481812
TI  - Automatic quantification of tibio-femoral contact area and congruity.
AB  - We present methods to quantify the medial tibio- femoral (MTF) joint contact area
      (CA) and congruity index (CI) from low-field magnetic resonance imaging (MRI).
      Firstly, based on the segmented MTF cartilage compartments, we computed the
      contact area using the Euclidian distance transformation. The CA was defined as
      the area of the tibial superior surface and the femoral inferior surface that are
      less than a voxel width apart. Furthermore, the CI is computed point-by-point by
      assessing the first- and second-order general surface features over the contact
      area. Mathematically, it is the inverse distance between the local normal vectors
      (first-order features) scaled by the local normal curvatures (second-order
      features) along the local direction of principal knee motion in a local reference
      coordinate system formed by the directions of principal curvature and the surface
      normal vector. The abilities of the CA and the CI for diagnosing osteoarthritis
      (OA) at different levels (disease severity was assessed using the Kellgren and
      Lawrence Index, KL) were cross-validated on 288 knees at baseline. Longitudinal
      analysis was performed on 245 knees. The precision quantified on 31 scan-rescan
      pairs (RMS CV) for CA was 13.7% and for CI 7.5%. The CA increased with onset of
      the disease and then decreased with OA progression. The CI was highest in healthy
      and decreased with the onset of OA and further with disease progression. The CI
      showed an AUC of 0.69 (p < 0.0001) for separating KL = 0 and KL > 0. For
      separating KL < 1 or KL = 1 and KL > 1 knees, the AUC for CI was 0.73 (p <
      0.0001). The CA demonstrated longitudinal responsiveness (SRM) at all stages of
      OA, whereas the CI did for advanced OA only. Eventually, the quantified CA and
      the CI might be suitable to help explaining OA onset, diagnosis of (early) OA,
      and measuring the efficacy of DMOADs in clinical trials.

PMID- 22481813
TI  - Spatial resolution properties of motion-compensated tomographic image
      reconstruction methods.
AB  - Many motion-compensated image reconstruction (MCIR) methods have been proposed to
      correct for subject motion in medical imaging. MCIR methods incorporate motion
      models to improve image quality by reducing motion artifacts and noise. This
      paper analyzes the spatial resolution properties of MCIR methods and shows that
      nonrigid local motion can lead to nonuniform and anisotropic spatial resolution
      for conventional quadratic regularizers. This undesirable property is akin to the
      known effects of interactions between heteroscedastic log-likelihoods (e.g.,
      Poisson likelihood) and quadratic regularizers. This effect may lead to
      quantification errors in small or narrow structures (such as small lesions or
      rings) of reconstructed images. This paper proposes novel spatial regularization
      design methods for three different MCIR methods that account for known nonrigid
      motion. We develop MCIR regularization designs that provide approximately uniform
      and isotropic spatial resolution and that match a user-specified target spatial
      resolution. Two-dimensional PET simulations demonstrate the performance and
      benefits of the proposed spatial regularization design methods.

PMID- 22481814
TI  - Quantitative assessment of lesion detection accuracy, resolution, and
      reconstruction algorithms in neutron stimulated emission computed tomography.
AB  - We present a quantitative analysis of the image quality obtained using filtered
      back-projection (FBP) with Ram-Lak filtering and maximum likelihood-expectation
      maximization (ML-EM)-with no post-reconstruction filtering in either case-in
      neutron stimulated emission computed tomography (NSECT) imaging using Monte Carlo
      simulations in the context of clinically relevant models of liver iron overload.
      The ratios of pixel intensities for several regions of interest and lesion shape
      detection using an active-contours segmentation algorithm are assessed for
      accuracy across different scanning configurations and reconstruction algorithms.
      The modulation transfer functions (MTFs) are also computed for the cases under
      study and are applied to determine a minimum detectable lesion spacing as a form
      of sensitivity analysis. The accuracy of NSECT imaging in measuring relative
      tissue concentration is presented for simulated clinical liver cases. When using
      the 15th iteration, ML-EM provides at least 25% better resolution than FBP and
      proves to be highly robust under low-signal high-noise conditions prevalent in
      NSECT. However, FBP gives more accurate lesion pixel intensity ratios and size
      estimates in some cases; due to advantages provided by both reconstruction
      algorithms, it is worth exploring the development of an algorithm that is a
      hybrid of the two. We also show that NSECT imaging can be used to accurately
      detect 3-cm lesions in backgrounds that are a significant fraction (one-quarter)
      of the concentration of the lesion, down to a 4-cm spacing between lesions.

PMID- 22481815
TI  - Human atlas of the cardiac fiber architecture: study on a healthy population.
AB  - Cardiac fibers, as well as their local arrangement in laminar sheets, have a
      complex spatial variation of their orientation that has an important role in
      mechanical and electrical cardiac functions. In this paper, a statistical atlas
      of this cardiac fiber architecture is built for the first time using human
      datasets. This atlas provides an average description of the human cardiac fiber
      architecture along with its variability within the population. In this study, the
      population is composed of ten healthy human hearts whose cardiac fiber
      architecture is imaged ex vivo with DT-MRI acquisitions. The atlas construction
      is based on a computational framework that minimizes user interactions and
      combines most recent advances in image analysis: graph cuts for segmentation,
      symmetric log-domain diffeomorphic demons for registration, and log-Euclidean
      metric for diffusion tensor processing and statistical analysis. Results show
      that the helix angle of the average fiber orientation is highly correlated to the
      transmural depth and ranges from -41 degrees  on the epicardium to +66 degrees 
      on the endocardium. Moreover, we find that the fiber orientation dispersion
      across the population (+/-13 degrees ) is lower than for the laminar sheets (+/
      31 degrees ) . This study, based on human hearts, extends previous studies on
      other mammals with concurring conclusions and provides a description of the
      cardiac fiber architecture more specific to human and better suited for clinical
      applications. Indeed, this statistical atlas can help to improve the
      computational models used for radio-frequency ablation, cardiac resynchronization
      therapy, surgical ventricular restoration, or diagnosis and followups of heart
      diseases due to fiber architecture anomalies.

PMID- 22481816
TI  - A probabilistic approach to realistic face synthesis with a single uncalibrated
      image.
AB  - This paper presents a novel approach to automatic face modeling for realistic
      synthesis from an unknown face image, using a probabilistic face diffuse model
      and a generic face specular map. We construct a probabilistic face diffuse model
      for estimating the albedo and normals of the input face. Then, we develop a
      generic face specular map for estimating the specularity of face. Using the
      estimated albedo, normal and specular information, we can synthesize the face
      under arbitrary lighting and viewing directions realistically. Unlike many
      existing techniques, our approach can extract both the diffuse and specular
      information of face without involving an intensive 3D matching procedure. We
      conduct three different experiments to show our improvement over the prior art.
      First, we compare the proposed algorithm with previous techniques, including the
      state of the art, to demonstrate our achievement in realistic face synthesis.
      Moreover, we evaluate the proposed algorithm over non-automatic face modeling
      techniques through a subjective study. This evaluation is meaningful in that it
      tells us how far the proposed algorithm as well as others are from the real
      photograph in terms of the perceptual quality. Finally, we apply our face model
      for improving the face recognition performance under varying illumination
      conditions and show that the proposed algorithm is effective to enhance the face
      recognition rate. Thanks to the compact representation and the effective
      inference scheme, our technique is applicable for many practical applications,
      such as avatar creation, digital face cloning, face normalization,
      deidentification and many others. 

PMID- 22481817
TI  - Modeling the performance of image restoration from motion blur.
AB  - When dealing with motion blur there is an inevitable trade-off between the amount
      of blur and the amount of noise in the acquired images. The effectiveness of any
      restoration algorithm typically depends on these amounts, and it is difficult to
      find their best balance in order to ease the restoration task. To face this
      problem, we provide a methodology for deriving a statistical model of the
      restoration performance of a given deblurring algorithm in case of arbitrary
      motion. Each restoration-error model allows us to investigate how the restoration
      performance of the corresponding algorithm varies as the blur due to motion
      develops. Our modeling treats the point-spread-function trajectories as random
      processes and, following a Monte-Carlo approach, expresses the restoration
      performance as the expectation of the restoration error conditioned on some
      motion-randomness descriptors and on the exposure time. This allows to coherently
      encompass various imaging scenarios, including camera shake and uniform
      (rectilinear) motion, and, for each of these, identify the specific exposure time
      that maximizes the image quality after deblurring. 

PMID- 22481818
TI  - Coupled dictionary training for image super-resolution.
AB  - In this paper, we propose a novel coupled dictionary training method for single
      image super-resolution based on patchwise sparse recovery, where the learned
      couple dictionaries relate the low- and high-resolution image patch spaces via
      sparse representation. The learning process enforces that the sparse
      representation of a low-resolution image patch in terms of the low-resolution
      dictionary can well reconstruct its underlying high-resolution image patch with
      the dictionary in the highresolution image patch space. We model the learning
      problem as a bilevel optimization problem, where the optimization includes an 1
      norm minimization problem in its constraints. Implicit differentiation is
      employed to calculate the desired gradient for stochastic gradient descent. We
      demonstrate that our coupled dictionary learning method can outperform the
      existing joint dictionary training method both quantitatively and qualitatively.
      Furthermore, for real applications, we speed up the algorithm approximately 10
      times by learning a neural network model for fast sparse inference and
      selectively processing only those visually salient regions. Extensive
      experimental comparisons with stateof- the-art super-resolution algorithms
      validate the effectiveness of our proposed approach. 

PMID- 22481819
TI  - Adaptive image decomposition into cartoon and texture parts optimized by the
      orthogonality criterion.
AB  - In this paper a new decomposition method is introduced that splits the image into
      geometric (or cartoon) and texture parts. Following a total variation based
      preprocesssing, the core of the proposed method is an anisotropic diffusion with
      an orthogonality based parameter estimation and stopping condition. The quality
      criterion is defined by the theoretical assumption that the cartoon and the
      texture components of an image should be orthogonal to each other. The presented
      method has been compared to other decomposition algorithms through visual and
      numerical evaluation to prove its superiority. 

PMID- 22481820
TI  - Discrete region competition for unknown numbers of connected regions.
AB  - We present a discrete, unsupervised multi-region competition algorithm for image
      segmentation over different energy functionals. The number of regions present in
      an image does not need to be known a priori, nor their photometric properties.
      The algorithm jointly estimates the number of regions, their photometries, and
      their contours. The required regularization is provided by defining a region as a
      connected set of pixels. The evolving contours in the image are represented by
      computational particles that move as driven by an energy-minimization algorithm.
      We present an efficient discrete algorithm that allows minimizing a range of well
      known energy functionals under the topological constraint of regions being
      connected components. The presented framework and algorithms are implemented in
      the open-source Insight Toolkit (ITK) image-processing library.

PMID- 22481821
TI  - Object detection with DoG scale-space: a multiple kernel learning approach.
AB  - Difference of Gaussians (DoG) scale-space for an image is a significant way to
      generate features for object detection and classification. While applying DoG
      scale-space features for object detection/classification, we face two inevitable
      issues: dealing with high dimensional data and selecting/weighting of proper
      scales. The scale selection process is mostly ad-hoc to date. In this paper, we
      propose a multiple kernel learning (MKL) method for both DoG scale
      selection/weighting and dealing with high dimensional scale-space data. We design
      a novel shift invariant kernel function for DoG scale-space. To select only the
      useful scales in the DoG scale-space, a novel framework of MKL is also proposed.
      We utilize a 1-norm support vector machine (SVM) in the MKL optimization problem
      for sparse weighting of scales from DoG scale-space. The optimized data-dependent
      kernel accommodates only a few scales that are most discriminatory according to
      the large margin principle. With a 2-norm SVM this learned kernel is applied to a
      challenging detection problem in oil sand mining: to detect large lumps in oil
      sand videos. We tested our method on several challenging oil sand data sets. Our
      method yields encouraging results on these difficult-to-process images and
      compares favorably against other popular multiple kernel methods. 

PMID- 22481822
TI  - Coupled kernel embedding for low resolution face image recognition.
AB  - Practical video scene and face recognition systems are sometimes confronted with
      low-resolution (LR) images. The faces may be very small even if the video is
      clear, thus it is difficult to directly measure the similarity between the faces
      and the high-resolution (HR) training samples. Traditional super-resolution (SR)
      methods based face recognition usually have limited performance because the
      target of SR may not be consistent with that of classification, and time
      consuming SR algorithms are not suitable for real-time applications. In this
      paper, a new feature extraction method called Coupled Kernel Embedding (CKE) is
      proposed for LR face recognition without any SR preprocessing. In this method,
      the final kernel matrix is constructed by concatenating two individual kernel
      matrices in the diagonal direction, and the (semi-)positively definite properties
      are preserved for optimization. CKE addresses the problem of comparing multi
      modal data that are difficult for conventional methods in practice due to the
      lack of an efficient similarity measure. Particularly, different kernel types
      (e.g., linear, Gaussian, polynomial) can be integrated into an uniformed
      optimization objective, which cannot be achieved by simple linear methods. CKE
      solves this problem by minimizing the dissimilarities captured by their kernel
      Gram matrices in the low- and high-resolution spaces. In the implementation, the
      nonlinear objective function is minimized by a generalized eigenvalue
      decomposition. Experiments on benchmark and real databases show that our CKE
      method indeed improves the recognition performance. 

PMID- 22481823
TI  - Inductive robust principal component analysis.
AB  - In this paper we address the error correction problem that is to uncover the low
      dimensional subspace structure from high-dimensional observations, which are
      possibly corrupted by errors. When the errors are of Gaussian distribution,
      Principal Component Analysis (PCA) can find the optimal (in terms of least-square
      error) low-rank approximation to highdimensional data. However, the canonical PCA
      method is known to be extremely fragile to the presence of gross corruptions.
      Recently, Wright et al. established a so-called Robust Principal Component
      Analysis (RPCA) method, which can well handle grossly corrupted data [14].
      However, RPCA is a transductive method and does not handle well the new samples
      which are not involved in the training procedure. Given a new datum, RPCA
      essentially needs to recalculate over all the data, resulting in high
      computational cost. So, RPCA is inappropriate for the applications that require
      fast online computation. To overcome this limitation, in this paper we propose an
      Inductive Robust Principal Component Analysis (IRPCA) method. Given a set of
      training data, unlike RPCA that targets on recovering the original data matrix,
      IRPCA aims at learning the underlying projection matrix, which can be used to
      efficiently remove the possible corruptions in any datum. The learning is done by
      solving a nuclear norm regularized minimization problem, which is convex and can
      be solved in polynomial time. Extensive experiments on a benchmark human face
      dataset and two video surveillance datasets show that IRPCA can not only be
      robust to gross corruptions, but also handle well the new data in an efficient
      way. 

PMID- 22481824
TI  - Shape error concealment based on a shape-preserving boundary approximation.
AB  - In objectbased video representation, video scenes are composed of several
      arbitrarily shaped video objects (VOs), defined by their texture, shape and
      motion. In errorprone communications, packet loss results in missing information
      at the decoder. The impact of transmission errors is minimised through error
      concealment. In this paper, we propose a spatial error concealment technique for
      recovering lost shape data. We consider a geometric shape representation
      consisting of the object boundary, which can be extracted from the -plane.
      Missing macroblocks result in a broken boundary. A Bspline curve is constructed
      to replace a missing boundary segment, based on a T spline representation of the
      received boundary. We use Tsplines because they produce shapepreserving
      approximations and do not change the characteristics of the original boundary.
      The representation ensures a good estimation of the first derivatives at the
      points touching the missing segment. Applying smoothing conditions, we manage to
      construct a new spline that joins smoothly with the received boundary, leading to
      successful concealment results. Experimental results on object shapes with
      different concealment difficulty demonstrate the performance of the proposed
      method. Comparisons with prior proposed methods are also presented. 

PMID- 22481825
TI  - Bistatic synthetic aperture radar imaging using ultraNarrowband continuous
      waveforms.
AB  - We consider synthetic aperture radar (SAR) imaging using ultra-narrowband
      continuous waveforms (CW). Due to the high Doppler resolution of CW signals, we
      refer to this imaging modality as Doppler Synthetic Aperture Radar (DSAR). We
      present a novel model and an image formation method for the bistatic DSAR for
      arbitrary imaging geometries. Our bistatic DSAR model is formed by correlating
      the translated version of the received signal with a scaled or frequencyshifted
      version of the transmitted CW signal over a finite time window. High frequency
      analysis of the resulting model shows that the correlated signal is the
      projections of the scene reflectivity onto the bistatic iso-Doppler curves. We
      next use microlocal techniques to develop a filtered-backprojection (FBP) type
      image reconstruction method. The FBP inversion results in backprojection of the
      correlated signal onto the bistatic iso- Doppler curves as opposed to the
      bistatic iso-range curves, performed in the traditional wideband SAR imaging. We
      show that our method takes advantage of the velocity, as well as the acceleration
      of the antennas in certain directions to form a high resolution SAR image. Our
      bistatic DSAR imaging method is applicable for arbitrary flight trajectories,
      nonflat topography, and can accommodate system related parameters. We present
      resolution analysis and extensive numerical experiments to demonstrate the
      performance of our imaging method. 

PMID- 22481826
TI  - Chromaticity space for illuminant invariant recognition.
AB  - In this paper an algorithm is proposed to extract two illuminant invariant
      chromaticity features from three image sensor responses. The algorithm extracts
      these chromaticity features at pixel level and therefore can perform well in
      scenes illuminated with non-uniform illuminant. An approach is proposed to use
      the algorithm with cameras of unknown sensitivity. The algorithm was tested for
      separability of perceptually similar colours under the International Commission
      on Illumination (CIE) standard illuminants and obtained a good performance. It
      was also tested for colour based object recognition by illuminating objects with
      typical indoor illuminants and obtained a better performance compared to other
      existing algorithms investigated in this paper. Finally, the algorithm was tested
      for skin detection invariant to illuminant, ethnic background and imaging device.
      In this investigation, daylight scenes under different weather conditions and
      scenes illuminated by typical indoor illuminants were used. The proposed
      algorithm gives a better skin detection performance compared to widely used
      standard colour spaces. Based on the results presented, the proposed illuminant
      invariant chromaticity space can be used for machine vision applications
      including illuminant invariant colour based object recognition and skin
      detection. 

PMID- 22481827
TI  - Collective Network of Binary Classifier Framework for Polarimetric SAR Image
      Classification: An Evolutionary Approach.
AB  - Terrain classification over polarimetric synthetic aperture radar (SAR) images
      has been an active research field where several features and classifiers have
      been proposed up to date. However, some key questions, e.g., 1) how to select
      certain features so as to achieve highest discrimination over certain classes?,
      2) how to combine them in the most effective way?, 3) which distance metric to
      apply?, 4) how to find the optimal classifier configuration for the
      classification problem in hand?, 5) how to scale/adapt the classifier if large
      number of classes/features are present?, and finally, 6) how to train the
      classifier efficiently to maximize the classification accuracy?, still remain
      unanswered. In this paper, we propose a collective network of (evolutionary)
      binary classifier (CNBC) framework to address all these problems and to achieve
      high classification performance. The CNBC framework adapts a "Divide and Conquer"
      type approach by allocating several NBCs to discriminate each class and performs
      evolutionary search to find the optimal BC in each NBC. In such an (incremental)
      evolution session, the CNBC body can further dynamically adapt itself with each
      new incoming class/feature set without a full-scale retraining or
      reconfiguration. Both visual and numerical performance evaluations of the
      proposed framework over two benchmark SAR images demonstrate its superiority and
      a significant performance gap against several major classifiers in this field. 

PMID- 22481828
TI  - Kinematic Bezier Maps.
AB  - The kinematics of a robot with many degrees of freedom is a very complex
      function. Learning this function for a large workspace with a good precision
      requires a huge number of training samples, i.e., robot movements. In this paper,
      we introduce the Kinematic Bezier Map (KB-Map), a parameterizable model without
      the generality of other systems but whose structure readily incorporates some of
      the geometric constraints of a kinematic function. In this way, the number of
      training samples required is drastically reduced. Moreover, the simplicity of the
      model reduces learning to solving a linear least squares problem. Systematic
      experiments have been carried out showing the excellent interpolation and
      extrapolation capabilities of KB-Maps and their relatively low sensitivity to
      noise. 

PMID- 22481829
TI  - Acceleration-Level Cyclic-Motion Generation of Constrained Redundant Robots
      Tracking Different Paths.
AB  - In this paper, a cyclic-motion generation (CMG) scheme at the acceleration level
      is proposed to remedy the joint-angle drift phenomenon of redundant robot
      manipulators which are controlled at the joint-acceleration level or torque
      level. To achieve this, a cyclic-motion criterion at the joint-acceleration level
      is exploited. This criterion, together with the joint-angle limits, joint
      velocity limits, and joint-acceleration limits, is considered into the scheme
      formulation. In addition, the neural-dynamic method of Zhang is employed to
      explain and analyze the effectiveness of the proposed criterion. Then, the scheme
      is reformulated as a quadratic program, which is solved by a primal-dual neural
      network. Furthermore, four tracking path simulations verify the effectiveness and
      accuracy of the proposed acceleration-level CMG scheme. Moreover, the comparisons
      between the proposed acceleration-level CMG scheme and the velocity-level scheme
      demonstrate that the former is safer and more applicable. The experiment on a
      physical robot system further verifies the physical realizability of the proposed
      acceleration-level CMG scheme. 

PMID- 22481830
TI  - Automatic segmentation of coronary arteries in CT imaging in the presence of
      kissing vessel artifacts.
AB  - In this paper, we present a novel two-step algorithm for segmentation of coronary
      arteries in computed tomography images based on the framework of active contours.
      In the proposed method, both global and local intensity information is utilized
      in the energy calculation. The global term is defined as a normalized cumulative
      distribution function, which contributes to the overall active contour energy in
      an adaptive fashion based on image histograms, to deform the active contour away
      from local stationary points. Possible outliers, such as kissing vessel
      artifacts, are removed in the postprocessing stage by a slice-by-slice correction
      scheme based on multiregion competition, where both arteries and kissing vessels
      are identified and tracked through the slices. The efficiency and the accuracy of
      the proposed technique are demonstrated on both synthetic and real datasets. The
      results on clinical datasets show that the method is able to extract the major
      branches of arteries with an average distance of 0.73 voxels to the manually
      delineated ground truth data. In the presence of kissing vessel artifacts, the
      outer surface of the entire coronary tree, extracted by the proposed algorithm,
      is smooth and contains fewer erroneous regions, originating in kissing vessel
      artifacts, as compared to the initial segmentation.

PMID- 22481831
TI  - Prediction of high-risk asymptomatic carotid plaques based on ultrasonic image
      features.
AB  - Carotid plaques have been associated with ipsilateral neurological symptoms. High
      resolution ultrasound can provide information not only on the degree of carotid
      artery stenosis but also on the characteristics of the arterial wall including
      the size and consistency of atherosclerotic plaques. The aim of this study is to
      determine whether the addition of ultrasonic plaque texture features to clinical
      features in patients with asymptomatic internal carotid artery stenosis (ACS)
      improves the ability to identify plaques that will produce stroke. 1121 patients
      with ACS have been scanned with ultrasound and followed for a mean of 4 years. It
      is shown that the combination of texture features based on second-order
      statistics spatial gray level dependence matrices (SGLDM) and clinical factors
      improves stroke prediction (by correctly predicting 89 out of the 108 cases that
      were symptomatic). Here, the best classification results of  77 +/-1.8% were
      obtained from the use of the SGLDM texture features with support vector machine
      classifiers. The combination of morphological features with clinical features
      gave slightly worse classification results of  76 +/-2.6% . These findings need
      to be further validated in additional prospective studies.

PMID- 22481832
TI  - A VLSI field-programmable mixed-signal array to perform neural signal processing
      and neural modeling in a prosthetic system.
AB  - A very-large-scale integration field-programmable mixed-signal array specialized
      for neural signal processing and neural modeling has been designed. This has been
      fabricated as a core on a chip prototype intended for use in an implantable
      closed-loop prosthetic system aimed at rehabilitation of the learning of a
      discrete motor response. The chosen experimental context is cerebellar classical
      conditioning of the eye-blink response. The programmable system is based on the
      intimate mixing of switched capacitor analog techniques with low speed digital
      computation; power saving innovations within this framework are presented. The
      utility of the system is demonstrated by the implementation of a motor classical
      conditioning model applied to eye-blink conditioning in real time with associated
      neural signal processing. Paired conditioned and unconditioned stimuli were
      repeatedly presented to an anesthetized rat and recordings were taken
      simultaneously from two precerebellar nuclei. These paired stimuli were detected
      in real time from this multichannel data. This resulted in the acquisition of a
      trigger for a well-timed conditioned eye-blink response, and repetition of
      unpaired trials constructed from the same data led to the extinction of the
      conditioned response trigger, compatible with natural cerebellar learning in
      awake animals.

PMID- 22481833
TI  - Pulse energy as a reliable reference for twitch forces induced by transcutaneous
      neuromuscular electrical stimulation.
AB  - Voltage-controlled neuromuscular electrical stimulation has been considered to be
      safer in noninvasive applications notwithstanding the fact that voltage
      controlled devices purportedly generate forces less predictable than their
      current-controlled equivalents. This prompted us to evaluate relevant electrical
      parameters to determine whether forces induced by voltage-controlled stimuli were
      able to match to those induced by current-controlled ones, which tend to evoke
      forces that were more predictable. Force magnitudes corresponding to current- and
      voltage-controlled stimuli were aligned with respect to electric charge
      (equivalent to average current intensity) and electrical energy (equivalent to
      average power) of the same stimulation pulse to determine which provided a better
      coherence. Consistency of forces evaluated with energy was significantly (p <
      0.001) better than that evaluated with electric charges, suggesting that
      electrically stimulated forces can be reliably predicted by monitoring the energy
      parameter of stimulation pulses. The above results appear to show that electrode
      tissue impedance, a factor that makes charge and energy evaluations different,
      redefined the actual effects of current intensities in generating favorable
      results. Accordingly, novel schemes that track the energy (or average power) of a
      stimulation pulse may be used as a reliable benchmark to associate mechanical
      (force) and electrical (stimulation pulse) characteristics in transcutaneous
      applications of electrical stimulation.

PMID- 22481834
TI  - Experimental validation of a hybrid computational model for selective stimulation
      using transverse intrafascicular multichannel electrodes.
AB  - Recently a hybrid model based on the finite element method and on a compartmental
      biophysical representation of peripheral nerve fibers and intraneural electrodes
      was developed founded on experimental physiological and histological data. The
      model appeared to be robust when dealing with uncertainties in parameter
      selection. However, an experimental validation of the findings provided by the
      model is required to fully characterize the potential of this approach. The
      recruitment properties of selective nerve stimulation using transverse
      intrafascicular multichannel electrodes (TIME) were investigated in this work in
      experiments with rats and were compared to model predictions. Animal experiments
      were performed using the same stimulation protocol as in the computer simulations
      in order to rigorously validate the model predictions and understand its
      limitations. Two different selectivity indexes were used, and new indexes for
      measuring electrode performance are proposed. The model predictions are in decent
      agreement with experimental results both in terms of recruitment curves and
      selectivity values. Results show that these models can be used for extensive
      studies targeting electrode shape design, active sites shape, and multipolar
      stimulation paradigms. From a neurophysiological point of view, the topographic
      organization of the rat sciatic nerve, on which the model was based, has been
      confirmed.

PMID- 22481835
TI  - Autocalibration and recurrent adaptation: towards a plug and play online ERD-BCI.
AB  - System calibration and user training are essential for operating motor imagery
      based brain-computer interface (BCI) systems. These steps are often unintuitive
      and tedious for the user, and do not necessarily lead to a satisfactory level of
      control. We present an Adaptive BCI framework that provides feedback after only
      minutes of autocalibration in a two-class BCI setup. During operation, the system
      recurrently reselects only one out of six predefined logarithmic bandpower
      features (10-13 and 16-24 Hz from Laplacian derivations over C3, Cz, and C4),
      specifically, the feature that exhibits maximum discriminability. The system then
      retrains a linear discriminant analysis classifier on all available data and
      updates the online paradigm with the new model. Every retraining step is preceded
      by an online outlier rejection. Operating the system requires no engineering
      knowledge other than connecting the user and starting the system. In a supporting
      study, ten out of twelve novice users reached a criterion level of above 70%
      accuracy in one to three sessions (10-80 min online time) of training, with a
      median accuracy of 80.2 +/- 11.3% in the last session. We consider the presented
      system a positive first step towards fully autocalibrating motor imagery BCIs.

PMID- 22481836
TI  - Constraining upper limb synergies of hemiparetic patients using a robotic
      exoskeleton in the perspective of neuro-rehabilitation.
AB  - The aim of this paper was to explore how an upper limb exoskeleton can be
      programmed to impose specific joint coordination patterns during rehabilitation.
      Based on rationale which emphasizes the importance of the quality of movement
      coordination in the motor relearning process, a robot controller was developed
      with the aim of reproducing the individual corrections imposed by a physical
      therapist on a hemiparetic patient during pointing movements. The approach
      exploits a description of the joint synergies using principal component analysis
      (PCA) on joint velocities. This mathematical tool is used both to characterize
      the patient's movements, with or without the assistance of a physical therapist,
      and to program the exoskeleton during active-assisted exercises. An original
      feature of this controller is that the hand trajectory is not imposed on the
      patient: only the coordination law is modified. Experiments with hemiparetic
      patients using this new active-assisted mode were conducted. Obtained results
      demonstrate that the desired inter-joint coordination was successfully enforced,
      without significantly modifying the trajectory of the end point.

PMID- 22481837
TI  - Magnetic tunnel junction design margin exploration for self-reference sensing
      scheme.
AB  - This work investigates the magnetic tunnel junction (MTJ) design requirements for
      the application of nondestructive self-reference sensing scheme, a novel sensing
      scheme featuring high tolerance of process variations, fast sensing speed, and no
      impact on device reliability. Unlike the conventional sensing scheme that
      requires a large TMR ratio and the uniform antiparallel and parallel resistances
      for MTJs, the nondestructive self-reference sensing scheme is more sensitive to
      the roll-off slope of MTJ's R-I or R-V curve. Our purpose is to provide a
      guidance to facilitate MTJ design used in the nondestructive self-reference
      scheme. In this work, we comprehensively investigate and analyze the design
      matrix by considering MTJ device physical properties, such as bias voltage
      dependent conductance, spin torque, etc. The manuscript suggests the approaches
      to optimize MTJ design for better trade-off between device properties and circuit
      design.

PMID- 22481838
TI  - Unilateral absence of a pulmonary artery: a rare disorder with variable
      presentation.
AB  - Unilateral absence of a pulmonary artery (UAPA) is a rare condition with an
      estimated prevalence of 1 in 200,000 young adults. Most commonly, UAPA occurs in
      conjunction with cardiovascular abnormalities such as tetralogy of Fallot or
      cardiac septal defects, but it can also occur in an isolated manner. Patients
      with isolated UAPA can remain asymptomatic into late adulthood but usually report
      symptoms such as dyspnea or chest pain or suffer from hemoptysis or recurrent
      infections. Diagnosis can be difficult due to the rarity of the condition and its
      nonspecific presentation. We present a case of a 61-year-old man who presented
      for lung transplant evaluation and was found to have UAPA. Typical findings on
      chest radiograph, strategies for diagnosis, and available treatments are
      discussed.

PMID- 22481839
TI  - Hepatitis E infection.

PMID- 22481840
TI  - Fatal aortic rupture from nonpenetrating chest trauma.

PMID- 22481841
TI  - High energy deficit in an ultraendurance athlete in a 24-hour ultracycling race.
AB  - This case study examined the nutritional behavior and energy balance in an
      official finisher of a 24-hour ultracycling race. The food and beverages consumed
      by the cyclist were continuously weighed and recorded to estimate intake of
      energy, macronutrients, sodium, and caffeine. In addition, during the race, heart
      rate was continuously monitored. Energy expenditure was assessed using a heart
      rate-oxygen uptake regression equation obtained previously from a laboratory
      test. The athlete (39 years, 175.6 cm, 84.2 kg, maximum oxygen uptake, 64
      mL/kg/min) cycled during 22 h 22 min, in which he completed 557.3 km with 8760 m
      of altitude at an average speed of 25.1 km/h. The average heart rate was 131
      beats/min. Carbohydrates were the main macronutrient intake (1102 g, 13.1 g/kg);
      however, intake was below current recommendations. The consumption of protein and
      fat was 86 g and 91 g, respectively. He ingested 20.7 L (862 mL/h) of fluids,
      with sport drinks the main fluid used for hydration. Sodium concentration in
      relation to total fluid intake was 34.0 mmol/L. Caffeine consumption over the
      race was 231 mg (2.7 mg/kg). During the race, he expended 15,533 kcal. Total
      energy intake was 5571 kcal, with 4058 (73%) and 1513 (27%) kcal derived from
      solids and fluids, respectively. The energy balance resulted in an energy deficit
      of 9915 kcal.

PMID- 22481842
TI  - The de novo diagnosis of systemic lupus erythematosus and lupus nephritis during
      pregnancy.

PMID- 22481843
TI  - A rare case of intraneural ganglion cyst involving the tibial nerve.
AB  - Cystic lesions around the knee are a relatively common occurrence. Several types
      of cysts have been reported, including synovial, bursal, and ganglion. Ganglion
      cysts are not lined by synovial cells. Their location is highly variable, with
      occurrences described in the fat pads near the tibia or femur, muscles, nerves,
      and arteries. Intraneural ganglia are rare nonneoplastic cysts caused by the
      accumulation of thick mucinous fluid within the epineurium of peripheral nerves,
      encased in a dense fibrous capsule. These cysts can cause compression of the
      adjacent nerve fascicles, resulting in pain, paresthesias, weakness, muscle
      denervation, and atrophy. They are most commonly manifested by local and
      radiating pain, but sensory and motor deficits have also been described.
      Involvement of the tibial nerve is exceptionally rare, with <15 reported cases in
      the literature. We present a case of intraneural tibial ganglion cyst in a young
      woman. We also discuss the imaging features, differential considerations,
      proposed pathogenesis and anatomic origin, and treatment of this rare entity.

PMID- 22481844
TI  - Jorge Felix Saucedo, MD, MBA: a conversation with the editor on optimizing
      antiplatelet and antithrombotic therapy in patients having percutaneous coronary
      intervention for acute coronary syndromes.

PMID- 22481845
TI  - Darwinian natural selection: its enduring explanatory power.
AB  - Evolutionary theory has never had a stronger scientific foundation than it does
      today. In a short review I hope to portray the deep commitment of today's
      biologists to Darwinian natural selection and to discoveries made since Darwin's
      time. In spite of the scientific advances in the century and a half since the
      publication of On the Origin of Species, Darwin still remains the principal
      author of modern evolutionary theory. He is one of the greatest contributors of
      all time to our understanding of nature.

PMID- 22481846
TI  - Extraadrenal pheochromocytoma and vagal paraganglioma.

PMID- 22481847
TI  - Widespread dermal ulcerations and bullae.
AB  - Bullous pemphigoid is an autoimmune disease of the skin characterized by large,
      tense bullae resulting in significant morbidity in affected individuals. The
      diagnosis of bullous pemphigoid may present challenges due to clinical
      similarities with various other bullous eruptions. Frequently, epidemiological
      features can provide clues to the diagnosis of bullous pemphigoid, with
      histologic analysis commonly required for definitive diagnosis. This case study
      illustrates the typical clinical and histologic findings seen in bullous
      pemphigoid patients and briefly discusses the differential diagnosis. An in-depth
      understanding of the intricate pathophysiology is essential in order to educate
      patients. After diagnosis and appropriate workup, an array of treatment
      approaches, including topical and systemic corticosteroids, immunosuppressive
      agents, antibiotics, chemotherapeutic agents, and even monoclonal antibodies, may
      be utilized individually or in combination to achieve an optimal therapeutic
      response.

PMID- 22481848
TI  - Irregular cardiac rhythm in a woman with asthma.

PMID- 22481849
TI  - Paget's disease of the calcaneus causing right foot pain.

PMID- 22481850
TI  - Ruptured cerebral arteriovenous malformation presenting as intraventricular
      hemorrhage.

PMID- 22481851
TI  - Tributes to george boswell, MD.

PMID- 22481852
TI  - Facts and ideas from anywhere.

PMID- 22481853
TI  - Thyroid Hormone-disrupting Effects and the Amphibian Metamorphosis Assay.
AB  - There are continued concerns about endocrine-disrupting chemical effects, and
      appropriate vertebrate models for assessment of risk are a high priority. Frog
      tadpoles are very sensitive to environmental substances because of their habitat
      and the complex processes of metamorphosis regulated by the endocrine system,
      mainly thyroid hormones. During metamorphosis, marked alteration in hormonal
      factors occurs, as well as dramatic structural and functional changes in larval
      tissues. There are a variety of mechanisms determining thyroid hormone balance or
      disruption directly or indirectly. Direct-acting agents can cause changes in
      thyroxine synthesis and/or secretion in thyroid through effects on peroxidases,
      thyroidal iodide uptake, deiodinase, and proteolysis. At the same time, indirect
      action may result from biochemical processes such as sulfation, deiodination and
      glucuronidation. Because their potential to disrupt thyroid hormones has been
      identified as an important consideration for the regulation of chemicals, the
      OECD and the EPA have each established guidelines that make use of larval African
      clawed frogs (Xenopus laevis) and frog metamorphosis for screening and testing of
      potential endocrine disrupters. The guidelines are based on evaluation of
      alteration in the hypothalamic-pituitary-thyroid axis. One of the primary
      endpoints is thyroid gland histopathology. Others are mortality, developmental
      stage, hind limb length, snout-vent length and wet body weight. Regarding
      histopathological features, the guidelines include core criteria and additional
      qualitative parameters along with grading. Taking into account the difficulties
      in evaluating amphibian thyroid glands, which change continuously throughout
      metamorphosis, histopathological examination has been shown to be a very
      sensitive approach.

PMID- 22481854
TI  - Carcinogen-induced Thyroid Proliferative Lesions in Wistar Hannover GALAS Rats
      with Thyroid Dysplasia.
AB  - Incidences and morphological features of thyroid proliferative lesions induced by
      carcinogens in Wistar Hannover GALAS rats (GALAS rats) showing normal growth with
      or without thyroid dysplasia were examined. All thyroid tissue samples were
      obtained from our recently conducted study using male GALAS rats treated with 5
      carcinogens according to the medium-term multiorgan carcinogenicity bioassay
      protocol (called DMBDD treatment). In the DMBDD-treated rats, thyroid dysplasia
      was found in 9 out of 114 rats. Follicular cell adenomas were found in 5 out of 9
      rats with thyroid dysplasia and in 7 out of 105 rats without thyroid dysplasia.
      The incidence of adenoma was significantly increased in rats with thyroid
      dysplasia (55.6%) compared with that in rats without thyroid dysplasia (6.7%).
      Adenomas in rats with thyroid dysplasia were observed as single or multiple
      nodules, well demarcated and composed of variously sized vacuolated cells or
      unvacuolated cells. These histopathological features and staining profiles of
      luminal colloid for PAS and thyroglobulin, together with PCNA-positive cells,
      were fundamentally similar to those of rats without thyroid dysplasia. On the
      other hand, the luminal colloid in adenomas of rats with thyroid dysplasia had a
      tendency to be poorly stained for T(4) compared with that of rats without thyroid
      dysplasia. From these findings, it appears that dysplastic thyroids of rats
      showing normal growth are more sensitive to carcinogens than normal thyroids. In
      addition, the morphological features of carcinogen-induced thyroid proliferative
      lesions in GALAS rats with thyroid dysplasia were fundamentally similar to those
      of rats without thyroid dysplasia, except for the vacuoles and T(4) staining
      profile.

PMID- 22481855
TI  - Ultrastructural and Immunohistochemical Studies on Uptake and Distribution of
      FITC-Conjugated PLGA Nanoparticles Administered Intratracheally in Rats.
AB  - Polylactide-glycolide (PLGA) nanoparticles have been developed as pulmonary drug
      delivery carriers. To investigate their behavior, small- (d50 = 74 nm) and large
      sized (d50 = 250 nm) FITC-conjugated PLGA nanoparticles were intratracheally
      administered to rats and were traced for 5, 30 and 60 minutes and 24 hours after
      administration (HAT). Immunohistochemically, a, FITC-positive reaction was
      observed in type-I alveolar epithelial cells (type-I AEC), endothelial cells and
      alveolar macrophages in the lungs from 5 minutes after treatment (MAT) to 24 HAT
      in both nanoparticle groups. In the kidneys, a positive reaction was observed in
      proximal tubular epithelial cells at 30 MAT; the reaction peaked at 60 MAT and
      was reduced at 24 HAT, while no positive reaction was seen in other sites.
      Ultrascructurally, the number of membrane-bound vesicles, which were
      approximately 70 nm in size and hard to distinguish from pinocytic vesicles,
      apparently increased in type-I AEC and endothelial cells at 5 MAT in the small
      sized group, in comparison with the control group receiving physiological saline.
      The number of vesicles in the large-sized group was almost same as that in the
      control group. On the other hand, in both nanoparticle groups, lysosomes filled
      with nanoparticles appeared in alveolar macrophages from 30 MAT to 24 HAT. These
      results indicate that PLGA nanoparticles might be quickly transferred from the
      alveolar space to the blood vessel via type-I alveolar epithelial cells and
      excreted into urine, and that there is a threshold for particle size, less than
      approximately 70 nm in diameter, with regard to absorption through the alveolar
      wall.

PMID- 22481857
TI  - Spontaneous thymoma in a 10-week-old sprague-dawley rat.
AB  - Spontaneous thymoma was found in the left lobe of the thymus of a male 10-week
      old Sprague-Dawley (SD) rat. Microscopically, the thymic mass showed a sheet of
      dark area with multiple pale foci. The dark area mainly consisted of densely
      compacted small lymphoid cells with sporadic large epithelioid cells and mitotic
      figures. The epithelioid cells and mitotic figures were more frequent than those
      of the normal thymic cortex in this animal. The multiple pale foci were similar
      to the normal thymic medulla and occasionally had Hassall's corpuscles; thus,
      they were regarded as medullary differentiation areas. Furthermore, some
      perivascular spaces recognized as characteristics of thymoma were present in the
      center of the mass. Immunohistochemically, the epithelioid cells in the dark area
      were positive for cytokeratin. Ultrastructurally, desmosomes and tonofilaments
      were observed in the epithelioid cells. Thus, this tumor was diagnosed as a
      thymoma. This is a rare case of thymoma occurring spontaneously in young adult SD
      rat.

PMID- 22481856
TI  - N -ethyl- N -nitrosourea induces retinal photoreceptor damage in adult rats.
AB  - Seven-week-old male Lewis rats received a single intraperitoneal injection of N
      ethyl-N-nitrosourea (ENU) (100, 200, 400 or 600 mg/kg), and retinal damage was
      evaluated 7 days after the treatment. Sequential morphological features of the
      retina and retinal DNA damage, as determined by a TUNEL assay and phospho-histone
      H2A.X (gamma-H2AX), were analyzed 3, 6, 12, 24 and 72 hr, 7 days, and/or 30 days
      after 400 mg/kg ENU treatment. Activation of the nuclear enzyme poly (ADP-ribose)
      polymerase (PARP) was analyzed immunohistochemically by poly (ADP-ribose) (PAR)
      expression in response to DNA damage of the retina. All rats that received >= 400
      mg/kg of ENU developed retinal degeneration characterized by the loss of
      photoreceptor cells in both the central and peripheral retina within 7 days. In
      the 400 mg/kg ENU-treated rats, TUNEL-positive signals were only located in the
      photoreceptor cells and peaked 24 hr after ENU treatment. The gamma-H2AX signals
      in inner retinal cells appeared at 24 hr and peaked at 72 hr after ENU treatment,
      and the PAR signals selectively located in the photoreceptor cell nuclei appeared
      at 12 hr and peaked at 24 hr after ENU treatment. However, degeneration was
      restricted to photoreceptor cells, and no degenerative changes in inner retinal
      cells were seen at any time points. Retinal thickness and the photoreceptor cell
      ratio in the central and peripheral retina were significantly decreased, and the
      retinal damage ratio was significantly increased 7 days after ENU treatment. In
      conclusion, ENU induced retinal degeneration in adult rats that was characterized
      by photoreceptor cell apoptosis through PARP activity.

PMID- 22481858
TI  - Porencephaly in a cynomolgus monkey ( macaca fascicularis ).
AB  - Porencephaly was observed in a female cynomolgus monkey (Macaca fascicularis)
      aged 5 years and 7 months. The cerebral hemisphere exhibited diffuse brownish
      excavation with partial defects of the full thickness of the hemispheric wall,
      and it constituted open channels between the lateral ventricular system and
      arachnoid space. In addition, the bilateral occipital lobe was slightly
      atrophied. Histopathologically, fibrous gliosis was spread out around the
      excavation area and its periphery. In the roof tissue over the cavity, small
      round cells were arranged in the laminae. They seemed to be neural or glial
      precursor cells because they were positive for Musashi 1 and negative for NeuN
      and GFAP. In the area of fibrous gliosis, hemosiderin or lipofuscin were
      deposited in the macrophages, and activated astroglias were observed extensively
      around the excavation area.

PMID- 22481859
TI  - Glaucoma in a New Zealand White Rabbit Fed High-cholesterol Diet.
AB  - Goniodysgenesis, malformation of the filtration angle, was observed in a New
      Zealand white rabbit supplied with 100 g/day rabbit chow containing 0.2%
      cholesterol for 10 months. Histopathology revealed cupping of the optic disc,
      atrophy of the retina and hyalinization of the ciliary body in the bilateral
      eyeballs. These findings corresponded with histopathological features caused by
      glaucoma. On the basis of these findings, we diagnosed this lesion as glaucoma,
      and classified it as primary glaucoma because of the presence of developmental
      defects of the filtration angle. In this case, hypercholesterolemia-induced
      changes, such as aggregation of lipid-laden macrophages and cholesterin clefts in
      the sclera or choroid, might cause deterioration of the lesions in glaucoma.

PMID- 22481860
TI  - Age Difference in Morphology and Immunohistology inthe Thymus and Spleen in
      Crl:CD (SD) Rats.
AB  - We investigated chronological changes in immunohistochemical phenotyping in the
      thymus and spleen in Crl:CD rats up to the age of about one year. In the thymus,
      T cells increased markedly from 3 to 4 weeks of age. Proliferating cells also
      increased markedly at these points. B cells tended towards an increase with age.
      In the spleen, white pulp increased until 9 weeks of age and remained fairly
      stable thereafter. In the periarteriolar lymphoid sheath and marginal zone, T
      cells gradually increased until 9 weeks of age and became almost flat thereafter.
      In the lymph follicle, T cells increased with age. B cells tended towards an
      increase with age in all areas of the spleen. It was concluded that development
      of the thymus was most marked from 3 to 4 weeks of age and that both the thymus
      and spleen had matured by 9 weeks of age.

PMID- 22481861
TI  - Histopathology of incidental findings in cynomolgus monkeys ( macaca fascicularis
      ) used in toxicity studies.
AB  - The purpose of our publication is to widely communicate pictures of spontaneous
      findings occurring in cynomolgus monkeys. Focal lymphoplasmacytic infiltration is
      commonly seen in the general organs. The frequency and severity of these lesions
      may be influenced by the administration of drugs with an effect on the immune
      system. Lymphoplasmacytic infiltration in the lamina propria of the stomach is
      also frequently seen in cynomolgus monkeys, and it is caused mainly by a
      Helicobacter pylori infection. Various degrees of brown pigments are observed in
      various organs, and it is possible to distinguish the material of the pigments by
      its morphological features and site. A focal/segmental glomerular lesion is
      occasionally seen in a section of the kidney, and the minimal lesion has no
      influence on the urinalysis. We showed the common glomerular lesions in HE
      stained sections, as well as in PAM- or PAS-stained sections, for understanding
      the details. Young and pubertal monkeys are usually used in toxicity studies;
      therefore, understanding various maturation stages of the genital system is
      important. In particular, the female genital system needs to be understood in the
      morphology, because their cyclic changes are different from other laboratory
      animals. Thus, we present the normal features of the cyclic changes of the female
      genital organs. Furthermore, we provide more information on spontaneous findings
      in cynomolgus monkeys for exact diagnoses in toxicity studies.

PMID- 22481862
TI  - Histopathology of incidental findings in beagles used in toxicity studies.
AB  - The purpose of our publication is to widely communicate the pictures of
      spontaneous findings occurring in beagles. Spontaneous arteritis occurs commonly
      in beagles. Frequent sites of arteritis are the heart, spleen, pancreas,
      epididymis and spinal cord. Morphological similarities between spontaneous and
      drug-induced arterial lesions may cause confusion when evaluating vascular
      toxicity of chemicals such as vasodilating agents. Focal and minimal inflammatory
      lesions are occasionally seen in the lung and may be associated with aspiration
      of food particles or of unknown causes. A cystic change with copious mucin
      production occurs occasionally in the mucosal epithelium of the gall bladder.
      Nesidioblastosis is seen rarely in the pancreas of beagles. C-cell complex and
      lymphocytic thyroiditis are common thyroid lesions. Spontaneous focal
      hypospermatogenesis and lobular Sertoli-cell-only seminiferous tubules occurring
      frequently in beagles must be distinguished from drug-induced damage of the
      seminiferous tubules in toxicity studies. The morphological differences of the
      female genital system in each cycle need to be understood; therefore, we present
      the normal features of the cyclic changes of the female genital organs. Further,
      we provide more information on spontaneous findings in beagles for exact
      diagnoses in toxicity studies.

PMID- 22481863
TI  - Cystic cholangioma in the thoracic cavity of a rat.
AB  - A female congenic rat produced by repeated backcrossing of Nihon rats, a model
      for hereditary renal cell carcinoma, to Brown Norway rats was necropsied at 24
      months of age. At necropsy, a white mass about 1 centimeter in size was observed
      in the thoracic cavity, and the mass partly adhered to the esophagus and the
      diaphragm. Histologically, the mass was clearly circumscribed by connective
      tissue, and consisted of neoplastic cuboidal epithelial cells that showed cystic
      tubular proliferation. Some islands of well-differentiated hepatocytes and some
      vessels were observed in the mass. Immunohistochemically, the tumor cells were
      strongly positive for cytokeratin and partly positive for vimentin but were
      negative for mesothelin and Von Willebrand Factor. The positive rate for Ki-67
      was 2.4%. Based on these histological and immunohistochemical evidences, we
      diagnosed this tumor as a cystic cholangioma that might have arisen from the
      ectopic hepatic tissue in the thoracic cavity.

PMID- 22481865
TI  - The impact of various reactive oxygen species on the formation of neutrophil
      extracellular traps.
AB  - The formation of neutrophil extracellular traps (NETs) depends on the generation
      of reactive oxygen species (ROS). Previous studies revealed that both NADPH
      oxidase and myeloperoxidase (MPO) are required for NET release. However, the
      contribution of various ROS as well as the role of mitochondria-derived ROS has
      not been addressed so far. In the present study we aimed to investigate in a
      systematic and comprehensive manner the contribution of various ROS and ROS
      generating pathways to the PMA-induced NET release. By using specific inhibitors,
      the role of both NADPH oxidase- and mitochondria-derived ROS as well as the
      contribution of superoxide dismutase (SOD) and MPO on the NET release was
      assessed. We could demonstrate that NADPH oxidase function is crucial for the
      formation of NETs. In addition, we could clearly show the involvement of MPO
      derived ROS in NET release. Our results, however, did not provide evidence for
      the role of SOD- or mitochondria-derived ROS in NET formation.

PMID- 22481864
TI  - Facts and fiction: the impact of hypothermia on molecular mechanisms following
      major challenge.
AB  - Numerous multiple trauma and surgical patients suffer from accidental
      hypothermia. While induced hypothermia is commonly used in elective cardiac
      surgery due to its protective effects, accidental hypothermia is associated with
      increased posttraumatic complications and even mortality in severely injured
      patients. This paper focuses on protective molecular mechanisms of hypothermia on
      apoptosis and the posttraumatic immune response. Although information regarding
      severe trauma is limited, there is evidence that induced hypothermia may have
      beneficial effects on the posttraumatic immune response as well as apoptosis in
      animal studies and certain clinical situations. However, more profound knowledge
      of mechanisms is necessary before randomized clinical trials in trauma patients
      can be initiated.

PMID- 22481866
TI  - A new experimental polytrauma model in rats: molecular characterization of the
      early inflammatory response.
AB  - BACKGROUND: The molecular mechanisms of the immune response after polytrauma are
      highly complex and far from fully understood. In this paper, we characterize a
      new standardized polytrauma model in rats based on the early molecular
      inflammatory and apoptotic response. METHODS: Male Wistar rats (250 g, 6
      10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury
      (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the
      following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI;
      (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as
      negative controls. The inflammatory response was quantified at 2 hours and 4
      hours after trauma by analysis of "key" inflammatory mediators, including
      selected cytokines and complement components, in serum and bronchoalveolar (BAL)
      fluid samples. RESULTS: Polytraumatized (PT) rats showed a significant systemic
      and intrapulmonary release of cytokines, chemokines, and complement
      anaphylatoxins, compared to rats with isolated injuries or selected combinations
      of injuries. CONCLUSION: This new rat model appears to closely mimic the early
      immunological response of polytrauma observed in humans and may provide a valid
      basis for evaluation of the complex pathophysiology and future therapeutic immune
      modulatory approaches in experimental polytrauma.

PMID- 22481867
TI  - The local inflammatory responses to infection of the peritoneal cavity in humans:
      their regulation by cytokines, macrophages, and other leukocytes.
AB  - Studies on infection-induced inflammatory reactions in humans rely largely on
      findings in the blood compartment. Peritoneal leukocytes from patients treated
      with peritoneal dialysis offer a unique opportunity to study in humans the
      inflammatory responses taking place at the site of infection. Compared with
      peritoneal macrophages (pMphi) from uninfected patients, pMphi from infected
      patients display ex vivo an upregulation and downregulation of proinflammatory
      and anti-inflammatory mediators, respectively. Pro-IL-1beta processing and
      secretion rather than synthesis proves to be increased in pMphi from infectious
      peritonitis suggesting up-regulation of caspase-1 in vivo. A crosstalk between
      pMphi, gammadelta T cells, and neutrophils has been found to be involved in
      augmented TNFalpha expression and production during infection. The recent finding
      in experimental studies that alternatively activated macrophages (Mphi2) increase
      by proliferation rather than recruitment may have significant implications for
      the understanding and treatment of chronic inflammatory conditions such as
      encapsulating peritoneal sclerosis (EPS).

PMID- 22481869
TI  - STGC3 inhibits xenograft tumor growth of nasopharyngeal carcinoma cells by
      altering the expression of proteins associated with apoptosis.
AB  - STGC3 is a potential tumor suppressor that inhibits the growth of the
      nasopharyngeal carcinoma cell line CNE2; the expression of this protein is
      reduced in nasopharyngeal carcinoma compared with normal nasopharyngeal tissue.
      In this study, we investigated the tumor-suppressing activity of STGC3 in nude
      mice injected subcutaneously with Tet/pTRE-STGC3/CNE2 cells. STGC3 expression was
      induced by the intraperitoneal injection of doxycycline (Dox). The volume mean of
      Tet/pTRE-STGC3/CNE2+Dox xenografts was smaller than that of Tet/pTRE/CNE2+Dox
      xenografts. In addition, Tet/pTRE-STGC3/CNE2+Dox xenografts showed an increase in
      the percentage of apoptotic cells, a decrease in Bcl-2 protein expression and an
      increase in Bax protein expression. A proteomic approach was used to assess the
      protein expression profile associated with STGC3-mediated apoptosis. Western
      blotting confirmed the differential up-regulation of prohibitin seen in proteomic
      analysis. These results indicate that overexpression of STGC3 inhibits xenograft
      growth in nude mice by enhancing apoptotic cell death through altered expression
      of apoptosis-related proteins such as Bcl-2, Bax and prohibitin. These data
      contribute to our understanding of the function of STGC3 in human nasopharyngeal
      carcinoma and provide new clues for investigating other STGC3-associated tumors.

PMID- 22481868
TI  - Trypanosomatid comparative genomics: Contributions to the study of parasite
      biology and different parasitic diseases.
AB  - In 2005, draft sequences of the genomes of Trypanosoma brucei, Trypanosoma cruzi
      and Leishmania major, also known as the Tri-Tryp genomes, were published. These
      protozoan parasites are the causative agents of three distinct insect-borne
      diseases, namely sleeping sickness, Chagas disease and leishmaniasis, all with a
      worldwide distribution. Despite the large estimated evolutionary distance among
      them, a conserved core of ~6,200 trypanosomatid genes was found among the Tri
      Tryp genomes. Extensive analysis of these genomic sequences has greatly increased
      our understanding of the biology of these parasites and their host-parasite
      interactions. In this article, we review the recent advances in the comparative
      genomics of these three species. This analysis also includes data on additional
      sequences derived from other trypanosmatid species, as well as recent data on
      gene expression and functional genomics. In addition to facilitating the
      identification of key parasite molecules that may provide a better understanding
      of these complex diseases, genome studies offer a rich source of new information
      that can be used to define potential new drug targets and vaccine candidates for
      controlling these parasitic infections.

PMID- 22481870
TI  - Distribution of the CCR5delta32 allele (gene variant CCR5) in Rondonia, Western
      Amazonian region, Brazil.
AB  - Since around 1723, on the occasion of its initial colonization by Europeans,
      Rondonia has received successive waves of immigrants. This has been further
      swelled by individuals from northeastern Brazil, who began entering at the
      beginning of the twentieth century. The ethnic composition varies across the
      state according to the various sites of settlement of each wave of immigrants. We
      analyzed the frequency of the CCR5Delta32 allele of the CCR5 chemokine receptor,
      which is considered a Caucasian marker, in five sample sets from the population.
      Four were collected in Porto Velho, the state capital and the site of several
      waves of migration. Of these, two, from the Hospital de Base were comprised of HB
      Mothers and HB Newborns presenting allele frequencies of 3.5% and 3.1%,
      respectively, a third from the peri-urban neighborhoods of Candelaria/Bate-Estaca
      (1.8%), whereas a fourth, from the Research Center on Tropical Medicine/CEPEM
      (0.6%), was composed of malaria patients under treament. The fifth sample (3.4%)
      came from the inland Quilombola village of Pedras Negras. Two homozygous
      individuals (CCR5Delta32/CCR5Delta32) were detected among the HB Mother samples.
      The frequency of this allele was heterogeneous and higher where the European
      inflow was more pronounced. The presence of the allele in Pedras Negras revealed
      European miscegenation in a community largely comprising Quilombolas.

PMID- 22481871
TI  - Assessment of genetic mutations in the XRCC2 coding region by high resolution
      melting curve analysis and the risk of differentiated thyroid carcinoma in Iran.
AB  - Homologous recombination (HR) is the major pathway for repairing double strand
      breaks (DSBs) in eukaryotes and XRCC2 is an essential component of the HR repair
      machinery. To evaluate the potential role of mutations in gene repair by HR in
      individuals susceptible to differentiated thyroid carcinoma (DTC) we used high
      resolution melting (HRM) analysis, a recently introduced method for detecting
      mutations, to examine the entire XRCC2 coding region in an Iranian population.
      HRM analysis was used to screen for mutations in three XRCC2 coding regions in 50
      patients and 50 controls. There was no variation in the HRM curves obtained from
      the analysis of exons 1 and 2 in the case and control groups. In exon 3, an
      Arg(188)His polymorphism (rs3218536) was detected as a new melting curve group
      (OR: 1.46; 95%CI: 0.432-4.969; p = 0.38) compared with the normal melting curve.
      We also found a new Ser(150)Arg polymorphism in exon 3 of the control group.
      These findings suggest that genetic variations in the XRCC2 coding region have no
      potential effects on susceptibility to DTC. However, further studies with larger
      populations are required to confirm this conclusion.

PMID- 22481872
TI  - Lack of evidence for intermolecular epistatic interactions between adiponectin
      and resistin gene polymorphisms in Malaysian male subjects.
AB  - Epistasis (gene-gene interaction) is a ubiquitous component of the genetic
      architecture of complex traits such as susceptibility to common human diseases.
      Given the strong negative correlation between circulating adiponectin and
      resistin levels, the potential intermolecular epistatic interactions between
      ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP
      420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type
      2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual
      influence of the ADIPOQ and RETN genes on their adipokine levels was also
      examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN
      locus tended to be co-inherited together with the common homozygous genotypes
      (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus.
      Despite the close structural relationship between the ADIPOQ and RETN genes,
      there was no evidence of an intermolecular epistatic interaction between these
      genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their
      adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect
      adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression
      warrants further investigation.

PMID- 22481873
TI  - Haplotype diversity of 17 Y-str loci in an admixed population from the Brazilian
      Amazon.
AB  - The allelic and haplotype frequencies of 17 Y-STR loci most commonly used in
      forensic testing were estimated in a sample of 138 unrelated healthy males from
      Macapa, in the northern Amazon region of Brazil. The average gene diversity was
      0.6554 +/- 0.3315. 134 haplotypes of the 17 loci were observed, 130 of them
      unique and four present in two individuals each. The haplotype diversity index
      was 0.9996 + 0.0009, with the most frequent haplogroups being R1b (52.2%), E1b1b
      (11.6%), J2 (10.1%) and Q (7.2%). Most haplogroups of this population belonged to
      European male lineages (89.2%), followed by Amerindian (7.2%) and African (3.6%)
      lineages.

PMID- 22481874
TI  - Medium-sized deletion in the BRCA1 gene: Limitations of Sanger sequencing and
      MLPA analyses.
AB  - We describe a family with a history of breast and ovarian cancer in which MLPA
      analysis of the BRCA1 gene pointed to a deletion including a part of exon 11.
      Further characterization confirmed a loss of 374 bp in a region completely
      covered by conventional sequencing which had not revealed the deletion. Because
      this alteration was only detected serendipitously with an MLPA probe, we
      calculated the probabilities of detecting medium-sized deletions in large exons
      by methods including initial PCR amplification. This showed that a considerable
      fraction of medium-sized deletions are undetectable by currently used standard
      methods of mutation analyses. We conclude that long, widely overlapping amplicons
      should be used to minimize the risk of missing medium-sized deletions.
      Alternatively, large exons could be completely covered by narrow-spaced MLPA
      probes.

PMID- 22481875
TI  - Cytogenetic characterization of F1, F2 and backcross hybrids of the Neotropical
      catfish species Pseudoplatystoma corruscans and Pseudoplatystoma reticulatum
      (Pimelodidae, Siluriformes).
AB  - The cytogenetic characteristics of Pseudoplatystoma corruscans and
      Pseudoplatystoma reticulatum and their F1, F2 and backcross hybrids were assessed
      by using chromosome banding techniques. The diploid number of 56 chromosomes was
      constant in all species and lineages, with a karyotypic formula containing 20
      metacentric, 12 submetacentric, 12 subtelocentric and 12 acrocentric chromosomes.
      Nucleolar organizer regions (NORs) were identified in two subtelocentric
      chromosomes in the parents and hybrids, with partial nucleolar dominance in F1
      and F2 specimens. Heterochromatic blocks were detected in the terminal and
      centromeric regions of some chromosomes in all individuals. For parental and
      hybrid lineages, 18S ribosomal clusters corresponding to NORs and 5S ribosomal
      genes were identified in distinct pairs of chromosomes. The striking conservation
      in the chromosomal macrostructure of the parental species may account for the
      fertility of their F1 hybrids. Similarly, the lack of marked alterations in the
      chromosomal structure of the F1 hybrids could account for the maintenance of
      these features in post-F1 lineages.

PMID- 22481876
TI  - Genetic structure and conservation of Mountain Lions in the South-Brazilian
      Atlantic Rain Forest.
AB  - The Brazilian Atlantic Rain Forest, one of the most endangered ecosystems
      worldwide, is also among the most important hotspots as regards biodiversity.
      Through intensive logging, the initial area has been reduced to around 12% of its
      original size. In this study we investigated the genetic variability and
      structure of the mountain lion, Puma concolor. Using 18 microsatellite loci we
      analyzed evidence of allele dropout, null alleles and stuttering, calculated the
      number of allele/locus, PIC, observed and expected heterozygosity, linkage
      disequilibrium, Hardy-Weinberg equilibrium, F(IS), effective population size and
      genetic structure (MICROCHECKER, CERVUS, GENEPOP, FSTAT, ARLEQUIN, ONESAMP, LDNe,
      PCAGEN, GENECLASS software), we also determine whether there was evidence of a
      bottleneck (HYBRIDLAB, BOTTLENECK software) that might influence the future
      viability of the population in south Brazil. 106 alleles were identified, with
      the number of alleles/locus ranging from 2 to 11. Mean observed heterozygosity,
      mean number of alleles and polymorphism information content were 0.609, 5.89, and
      0.6255, respectively. This population presented evidence of a recent bottleneck
      and loss of genetic variation. Persistent regional poaching constitutes an
      increasing in the extinction risk.

PMID- 22481877
TI  - Polymorphic heterologous microsatellite loci for population genetics studies of
      the white-faced ibis Plegadis chihi (Vieillot, 1817) (Pelecaniformes,
      Threskiornithidae).
AB  - We screened 44 heterologous microsatellites isolated in species of the families
      Threskiornithidae, Ciconiidae and Ardeidae for their use in a migratory
      waterbird, the white-faced ibis Plegadis chihi (Vieillot, 1817)
      (Threskiornithidae). Of the screened loci, 57% amplified successfully and 24%
      were polymorphic. In two breeding colonies from southern Brazil (N = 131) we
      detected 32 alleles (2-10 alleles/locus). Average He over all loci and colonies
      was 0.55, and the combined probability of excluding false parents, 98%. There was
      no departure from HWE in any loci or population. Eru6 and Eru4 loci were in non
      random association in the Alvorada colony, and NnNF5 and Eru5 in both
      populations. AMOVA analysis indicated that most of the genetic diversity was
      contained within populations. Structure analysis suggested a single population,
      and F(ST) value showed weak genetic structuring (F(ST) = 0.009, p = 0.05). The
      two populations are apparently connected through gene-flow. The panel of six
      microsatellites optimized here was sufficiently informative for characterizing
      the genetic diversity and structure in these natural populations of the white
      faced ibis. The information generated could be useful in future studies of
      genetic diversity, relatedness and the mating system in Plegadis chihi and
      related species.

PMID- 22481878
TI  - Sequence variation in the melanocortin-1 receptor (MC1R) pigmentation gene and
      its role in the cryptic coloration of two South American sand lizards.
AB  - In reptiles, dorsal body darkness often varies with substrate color or
      temperature environment, and is generally presumed to be an adaptation for
      crypsis or thermoregulation. However, the genetic basis of pigmentation is poorly
      known in this group. In this study we analyzed the coding region of the
      melanocortin-1-receptor (MC1R) gene, and therefore its role underlying the dorsal
      color variation in two sympatric species of sand lizards (Liolaemus) that inhabit
      the southeastern coast of South America: L. occipitalis and L. arambarensis. The
      first is light-colored and occupies aeolic pale sand dunes, while the second is
      brownish and lives in a darker sandy habitat. We sequenced 630 base pairs of MC1R
      in both species. In total, 12 nucleotide polymorphisms were observed, and four
      amino acid replacement sites, but none of them could be associated with a color
      pattern. Comparative analysis indicated that these taxa are monomorphic for amino
      acid sites that were previously identified as functionally important in other
      reptiles. Thus, our results indicate that MC1R is not involved in the
      pigmentation pattern observed in Liolaemus lizards. Therefore, structural
      differences in other genes, such as ASIP, or variation in regulatory regions of
      MC1R may be responsible for this variation. Alternatively, the phenotypic
      differences observed might be a consequence of non-genetic factors, such as
      thermoregulatory mechanisms.

PMID- 22481879
TI  - Karyological analysis of Proechimys cuvieri and Proechimys guyannensis (Rodentia,
      Echimyidae) from central Amazon.
AB  - The aim was to characterize the karyotype of rodents of the genus Proechimys from
      three localities in the central Brazilian Amazon, in the search for new markers
      that might shed light on our understanding of the taxonomy and evolutionary
      history of this taxon. Two karyotypes were found, viz., 2n = 28, FN = 46 in
      individuals from the NRSP (Cuieiras River) and REMAN (Manaus), and 2n = 46, FN =
      50 in individuals from the Balbina Hydroelectric Plant. While individuals with
      the karyotype with 2n = 28 chromosomes were morphologically associated with
      Proechimys cuvieri, their karyotype shared similarities with those of the same
      diploid number in two other regions. Although three karyotypes are described for
      Proechimys cuvieri, no geographic distribution pattern that defined a cline could
      be identified. Based on the morphological examination of voucher specimens and
      additional results from molecular analysis, the karyotype with 2n = 46 and FN =
      50 could be associated with P. guyannensis.

PMID- 22481880
TI  - Molecular characterization of MHC-DRB cDNA in water buffalo (Bubalus bubalis).
AB  - In the present study, water buffalo MHC (Bubu)-DRB cDNA was cloned and
      characterized. The 1022 base long-amplified cDNA product encompassed a single
      open reading frame of 801 bases that coded for 266 amino acids. The Bubu-DRB
      sequence showed maximum homology with the BoLA-DRB3*0101 allele of cattle. A
      total of seven amino acid residues were found to be unique for the Bubu-DRB
      sequence. The majority of amino acid substitutions was observed in the beta(1)
      domain. Residues associated with important functions were mostly conserved. Water
      buffalo DRB was phylogenetically closer to goat DRB*A.

PMID- 22481881
TI  - Population genetic structure of Sisyrinchium micranthum Cav. (Iridaceae) in
      Itapua State Park, Southern Brazil.
AB  - Sisyrinchium micranthum Cav. is a member of the family Iridaceae, which is
      distributed over the American continent. In Brazil, this species is found, not
      only in disturbed areas and coastal regions, but is also very common in urban
      centers, such as public parks, during the spring. Chromosome counts for North
      American specimens are 2n = 32 and 2n = 48, whereas in southern Brazil, there is
      a polyploidy series with three chromosome numbers, 2n = 16, 2n = 32, and 2n = 48.
      Population analyses using DNA molecular markers are inexistent for this species,
      in spite of its wide distribution and morphological variation. To study the
      genetic population structure of S. micranthum, five natural populations were
      accessed in a conservation park within the Atlantic Rain Forest Biome in southern
      Brazil. Here, the chromosome numbers 2n = 16 and 2n = 48 had already been
      described. Molecular analysis showed that the populations are highly structured
      with low gene flow among them. The population with 2n = 48 was genetically less
      variable than and distinct from the other populations. Population genetics in
      relation to cytogenetic data provided new insights regarding the genetic
      diversification and mating system of S. micranthum.

PMID- 22481882
TI  - Genetic architecture of purple pigmentation and tagging of some loci to SSR
      markers in pearl millet, Pennisetum glaucum (L.) R. Br.
AB  - This report describes the construction of integrated genetic maps in pearl millet
      involving certain purple phenotype and simple sequence repeat (SSR) markers.
      These maps provide a direct means of implementing DNA marker-assisted selection
      and of facilitating "map-based cloning" for engineering novel traits. The purple
      pigmentation of leaf sheath, midrib and leaf margin was inherited together 'en
      bloc' under the control of a single dominant locus (the 'midrib complex') and was
      inseparably associated with the locus governing the purple coloration of the
      internode. The purple panicle was caused by a single dominant locus. Each of the
      three characters (purple lamina, purple stigma and purple seed) was governed by
      two complementary loci. One of the two loci governing purple seed was associated
      with the SSR locus Xpsmp2090 in linkage group 1, with a linkage value of 22 cM,
      while the other locus was associated with the SSR locus Xpsmp2270 in linkage
      group 6, with a linkage value of 23 cM. The locus for purple pigmentation of the
      midrib complex was either responsible for pigmentation of the panicle in a
      pleiotropic manner or was linked to it very closely and associated with the SSR
      locus Xpsmp2086 in linkage group 4, with a suggestive linkage value of 21 cM. A
      dominant allele at this locus seems to be a prerequisite for the development of
      purple pigmentation in the lamina, stigma and seed. These findings suggest that
      the locus for pigmentation of the midrib complex might regulate the basic steps
      in anthocyanin pigment development by acting as a structural gene while other
      loci regulate the formation of color in specific plant parts.

PMID- 22481883
TI  - The genetic structure and mating system of Acrocomia aculeata (Arecaceae).
AB  - Acrocomia aculeata is a perennial, fruit-producing palm tree, native to tropical
      forests. Its fruits have spurred interest because of their significant potential
      for use in the cosmetic industry and as feedstock for biofuel. In the present
      study, the genetic structure and mating system in Acrocomia aculeata were
      analyzed, using eight nuclear micro-satellite loci and samples from Sao Paulo and
      Minas Gerais states, Brazil. By means of Bayesian analysis, these populations
      were clustered into two or three groups. A high multilocus outcrossing rate
      suggests that outcrosses were predominant, although a certain degree of
      biparental inbreeding also occurred. Thus, although monoecious and self
      compatible, there is every indication that A. aculeata bears a mixed reproductive
      system, with a predominance of outcrossing. Given the genetic structure revealed
      hereby, future conservation strategies and germplasm collecting should be
      focussed on sampling and preserving individuals from different clusters.

PMID- 22481884
TI  - Molecular identification of Pichia guilliermondii, Debaryomyces hansenii and
      Candida palmioleophila.
AB  - Traditional phenotypic methods and commercial kits based on carbohydrate
      assimilation patterns are unable to consistently distinguish among isolates of
      Pichia guilliermondii, Debaryomyces hansenii and Candida palmioleophila. As
      result, these species are often misidentified. In this work, we established a
      reliable method for the identification/differentiation of these species. Our
      assay was validated by DNA sequencing of the polymorphic region used in a real
      time PCR assay driven by species-specific probes targeted to the fungal ITS 1
      region. This assay provides a new tool for pathogen identification and for
      epidemiological, drug resistance and virulence studies of these organisms.

PMID- 22481885
TI  - Diversity and three-dimensional structures of the alpha Mcr of the methanogenic
      Archaea from the anoxic region of Tucurui Lake, in Eastern Brazilian Amazonia.
AB  - Methanogenic archaeans are organisms of considerable ecological and
      biotechnological interest that produce methane through a restricted metabolic
      pathway, which culminates in the reaction catalyzed by the Methyl-coenzyme M
      reductase (Mcr) enzyme, and results in the release of methane. Using a
      metagenomic approach, the gene of the alpha subunit of mcr (mcralpha) was
      isolated from sediment sample from an anoxic zone, rich in decomposing organic
      material, obtained from the Tucurui hydroelectric dam reservoir in eastern
      Brazilian Amazonia. The partial nucleotide sequences obtained were 83 to 95%
      similar to those available in databases, indicating a low diversity of archaeans
      in the reservoir. Two orders were identified - the Methanomicrobiales, and a
      unique Operational Taxonomic Unit (OTU) forming a clade with the
      Methanosarcinales according to low bootstrap values. Homology modeling was used
      to determine the three-dimensional (3D) structures, for this the partial
      nucleotide sequence of the mcralpha were isolated and translated on their partial
      amino acid sequences. The 3D structures of the archaean Mcralpha observed in the
      present study varied little, and presented approximately 70% identity in
      comparison with the Mcralpha of Methanopyrus klanderi. The results demonstrated
      that the community of methanogenic archaeans of the anoxic C1 region of the
      Tucurui reservoir is relatively homogeneous.

PMID- 22481886
TI  - Microbial diversity of soils on the banks of the Solimoes and Negro rivers, state
      of Amazonas, Brazil.
AB  - Analysis of bacterial diversity in soils along the banks of the Solimoes and
      Negro rivers, state of Amazonas, Brazil, was by partial sequencing of the genes
      codifying the rDNA16S region. Diversity of operational taxonomic units (OTU) and
      of the divergent sequences obtained were applied in comparative analysis of
      microbiological diversity in the two environments, based on richness estimators
      and OTU diversity indices. The higher OTU diversity in the Solimoes was based on
      the higher number of parameters that evoke this. The interaction between the
      nucleotide sequences of bacteria inhabiting the two riverine environments
      indicated that the two microrganism communities are similar in composition.

PMID- 22481887
TI  - Analysis of 16S rRNA and mxaF genes revealing insights into Methylobacterium
      niche-specific plant association.
AB  - The genus Methylobacterium comprises pink-pigmented facultative methylotrophic
      (PPFM) bacteria, known to be an important plant-associated bacterial group.
      Species of this group, described as plant-nodulating, have the dual capacity of
      producing cytokinin and enzymes, such as pectinase and cellulase, involved in
      systemic resistance induction and nitrogen fixation under specific plant
      environmental conditions. The aim hereby was to evaluate the phylogenetic
      distribution of Methylobacterium spp. isolates from different host plants. Thus,
      a comparative analysis between sequences from structural (16S rRNA) and
      functional mxaF (which codifies for a subunit of the enzyme methanol
      dehydrogenase) ubiquitous genes, was undertaken. Notably, some Methylobacterium
      spp. isolates are generalists through colonizing more than one host plant,
      whereas others are exclusively found in certain specific plant-species.
      Congruency between phylogeny and specific host inhabitance was higher in the mxaF
      gene than in the 16S rRNA, a possible indication of function-based selection in
      this niche. Therefore, in a first stage, plant colonization by Methylobacterium
      spp. could represent generalist behavior, possibly related to microbial
      competition and adaptation to a plant environment. Otherwise, niche-specific
      colonization is apparently impelled by the host plant.

PMID- 22481888
TI  - Xylella fastidiosa comparative genomic database is an information resource to
      explore the annotation, genomic features, and biology of different strains.
AB  - The Xylella fastidiosa comparative genomic database is a scientific resource with
      the aim to provide a user-friendly interface for accessing high-quality manually
      curated genomic annotation and comparative sequence analysis, as well as for
      identifying and mapping prophage-like elements, a marked feature of Xylella
      genomes. Here we describe a database and tools for exploring the biology of this
      important plant pathogen. The hallmarks of this database are the high quality
      genomic annotation, the functional and comparative genomic analysis and the
      identification and mapping of prophage-like elements. It is available from web
      site http://www.xylella.lncc.br.

PMID- 22481889
TI  - Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells.
AB  - Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers
      fasting plasma-insulin concentration, wherefore it's wide use for patients with a
      variety of insulin-resistant and prediabetic states, including impaired glucose
      tolerance. During pregnancy it is a further resource for reducing first-trimester
      pregnancy loss in women with the polycystic ovary syndrome. We tested metformin
      genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations;
      comet assays) and in mice (micronucleus assays). Concentrations of 114.4 MUg/mL
      and 572 MUg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9
      mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations
      in metaphase cells, DNA damage was detected by comet assaying after 24 h of
      incubation at both concentrations. The frequency of DNA damage was higher at
      concentrations of 114.4 MUg/mL. Furthermore, although mortality was not observed
      in in vitro tests, the highest dose of metformin suppressed bone marrow cells.
      However, no statistically significant differences were noted in micronuclei
      frequencies between treatments. In vitro results indicate that chronic metformin
      exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment
      with metformin should be properly evaluated beforehand, as regards vulnerability
      to DNA damage.

PMID- 22481890
TI  - The cytotoxic and growth inhibitory effects of palladium(II) complexes on MDA-MB
      435 cells.
AB  - The antitumorigenic potential of two palladium(II) complexes, [Pd(ca(2)-o
      phen)Cl(2)] - C1 and [Pd(dmba)(dppp)Cl] - C2, was evaluated, using MDA-MB-435
      cells, a human breast adenocarcinoma cell-line that does not express the estrogen
      receptor alpha (ER-). Growth inhibition and induced alterations in cell
      morphology were analyzed. The sulforhodamine B test showed that, compared to
      control cells, both C1 and C2 significantly inhibited (p < 0.5) cell growth. The
      maximum effect with both was achieved with 1 MUM complexes, after 24 h of
      treatment. No further cell-growth inhibition was achieved by increasing
      concentration or incubation time. Cell morphology was analyzed after staining
      with hematoxylin-eosin (HE). The morphological changes noted in the treated cells
      were cell rounding-up, shrinkage, nuclear condensation and reduction of cell
      length (p < 0.05), thereby indicating that both C1 and C2 are cytotoxic to breast
      adenocarcinoma cells. All together, there was every indication that, by
      decreasing cell growth and inducing morphological changes, the tested complexes
      are cytotoxic, hence their potentiality as promising candidates for
      antineoplastic drug development.

PMID- 22481891
TI  - Multi-target siRNA based on DNMT3A/B homologous conserved region influences cell
      cycle and apoptosis of human prostate cancer cell line TSU-PR1.
AB  - Abnormal genome hypermethylation participates in the tumorigenesis and
      development of prostate cancer. Prostate cancer cells highly express DNA
      methyltransferase 3 (DMNT3) family genes, essential for maintaining genome
      methylation. In the present study, multi-target siRNA, based on the homologous
      region of the DNMT3 family, was designed for the in vitro investigation of its
      effects on the proliferation, migration, and invasion of TSU-PR1 prostate cancer
      cells. The consequential cell-cycle derangement, through DNMT3A/B or only DNMT3B
      silencing, was partially efficient, without affecting apoptosis. DNMT3A silencing
      had absolutely no effect on changing TSU-PR1 cell biological behavior. Hence,
      DNMT3B alone apparently plays a key role in maintaining the unfavorable behavior
      of prostate-cancer cells, thereby implying its potential significance as a
      promising therapeutic target, with DNMT3A simply in the role of helper.

PMID- 22481892
TI  - Cloning and expression of embryogenesis-regulating genes in Araucaria
      angustifolia (Bert.) O. Kuntze (Brazilian Pine).
AB  - Angiosperm and gymnosperm plants evolved from a common ancestor about 300 million
      years ago. Apart from morphological and structural differences in embryogenesis
      and seed origin, a set of embryogenesis-regulating genes and the molecular
      mechanisms involved in embryo development seem to have been conserved alike in
      both taxa. Few studies have covered molecular aspects of embryogenesis in the
      Brazilian pine, the only economically important native conifer in Brazil. Thus
      eight embryogenesis-regulating genes, viz., ARGONAUTE 1, CUP-SHAPED COTYLEDON 1,
      WUSCHEL-related WOX, S-LOCUS LECTIN PROTEIN KINASE, SCARECROW-like, VICILIN 7S,
      LEAFY COTYLEDON 1, and REVERSIBLE GLYCOSYLATED POLYPEPTIDE 1, were analyzed
      through semi-quantitative RT-PCR during embryo development and germination. All
      the eight were found to be differentially expressed in the various developmental
      stages of zygotic embryos, seeds and seedling tissues. To our knowledge, this is
      the first report on embryogenesis-regulating gene expression in members of the
      Araucariaceae family, as well as in plants with recalcitrant seeds.

PMID- 22481893
TI  - Molecular cloning and in silico analysis of the duck (Anas platyrhynchos) MEF2A
      gene cDNA and its expression profile in muscle tissues during fetal development.
AB  - The role of myogenic enhancer transcription factor 2a (MEF2A) in avian muscle
      during fetal development is unknown. In this work, we cloned the duck MEF2A cDNA
      sequence (GenBank accession no. HM460752) and examined its developmental
      expression profiles in cardiac muscle, non-vascular smooth muscle and skeletal
      muscle. Duck MEF2A cDNA comprised 1479 bp encoding 492 amino acid residues. In
      silico analysis showed that MEF2A contained MADS (MCM1, AGAMOUS, DEFICIENS and
      SRF - serum response factor), MEF2 and mitogen-activated protein kinase (MAPK)
      transcription domains with high homology to related proteins in other species.
      Modified sites in these domains were conserved among species and several variants
      were found. Quantitative PCR showed that MEF2A was expressed in all three muscles
      at each developmental stage examined, with the expression in smooth muscle being
      higher than in the other muscles. These results indicate that the conserved
      domains of duck MEF2A, including the MADS and MEF2 domains, are important for
      MEF2A transcription factor function. The expression of MEF2A in duck smooth
      muscle and cardiac muscle suggests that MEF2A plays a role in these two tissues.

PMID- 22481894
TI  - The complete mitochondrial genome of the small yellow croaker and partitioned
      Bayesian analysis of Sciaenidae fish phylogeny.
AB  - To understand the phylogenetic position of Larimichthys polyactis within the
      family Sciaenidae and the phylogeny of this family, the organization of the
      mitochondrial genome of small yellow croaker was determined herein. The complete,
      16,470 bp long, mitochondrial genome contains 37 mitochondrial genes (13 protein
      coding, 2 ribosomal RNA and 22 transfer RNA genes), as well as a control region
      (CR), as in other bony fishes. Comparative analysis of initiation/termination
      codon usage in mitochondrial protein-coding genes of Percoidei species, indicated
      that COI in Sciaenidae entails an ATG/AGA codon usage different from other
      Percoidei fishes, where absence of a typical conserved domain or motif in the
      control regions is common. Partitioned Bayesian analysis of 618 bp of COI
      sequences data were used to infer the phylogenetic relationships within the
      family Sciaenidae. An improvement in harmonic mean -lnL was observed when
      specific models and parameter estimates were assumed for partitions of the total
      data. The phylogenetic analyses did not support the monophyly of Otolithes,
      Argyrosomus, and Argyrosominae. L. polyactis was found to be most closely related
      to Collichthys niveatus, whereby, according to molecular systematics studies, the
      relationships within the subfamily Pseudosciaenidae should be reconsidered.

PMID- 22481895
TI  - Holotranscobalamin is a useful marker of vitamin B12 deficiency in alcoholics.
AB  - BACKGROUND: Measurement of serum cobalamin (Cbl) levels is the standard
      investigation for assessing vitamin B12 deficiency. Falsely increased values of
      Cbl can be caused by alcoholic liver disease. Measurement of total vitamin B12
      serum levels might be misleading in alcoholics, because a tissue metabolic
      deficiency is possible even with normal serum Cbl levels. Holotranscobalamin
      (HoloTC), the Cbl metabolically active fraction, is considered as a better index
      of vitamin B12 deficiency. METHODS: For assessing vitamin B12 status, we
      evaluated 22 adult alcoholic male patients by measuring in parallel serum Cbl,
      serum folate and red blood cell folate levels, HoloTC levels by the AxSYM assay.
      RESULTS. HoloTC values were reduced in 3 alcoholics with borderline-low Cbl
      values. Significant positive correlations were found between serum Cbl and HoloTC
      levels, serum Cbl and gamma-glutamyl transpeptidase (GGT). CONCLUSION: HoloTC
      measurement is a useful option for assessing vitamin B12 status in alcoholics,
      particularly in the subjects with borderline Cbl values and may be considered an
      early marker of vitamin B12 deficiency.

PMID- 22481897
TI  - All-enzymatic HPLC method for determination of individual and total contents of
      vitamin B(6) in foods.
AB  - BACKGROUND: There is a need for a reliable and accurate method for quantification
      of each of the seven individual vitamin B(6) compounds including pyridoxine-beta
      glucoside in foods. OBJECTIVE: To determine pyridoxal (PL), pyridoxamine (PM),
      pyridoxine (PN), pyridoxal 5'-phosphate (PLP), pyridoxamine 5'-phosphate (PMP),
      pyridoxine 5'-phosphate (PNP), and pyridoxine-beta-glucoside (PNG) in foods.
      DESIGN: By specific enzymatic treatment, each of the seven vitamin B(6) compounds
      was all converted into 4-pyridoxolactone, which is a highly fluorescent compound.
      In total, seven separate, enzymatic steps were performed for each sample.
      Separation and quantification were performed with reversed-phase high performance
      liquid chromatography (HPLC) coupled with fluorescence detection. For each sample
      type the result was corrected for the recovery based on spiked samples. The
      method was applied for analyses of chicken liver, chicken white meat, egg yolk,
      egg white, dried anchovy, carrots, and garlic. RESULTS: The recovery varied from
      14 to 114% in chicken liver, chicken white meat, egg yolk, egg white, dried
      anchovy, carrot, and garlic. Each food showed a characteristic distribution of
      the seven vitamin B(6) compounds. The PNG was only found in low amounts; that is,
      17-29nmol vitamin B(6)/g in the plant-derived foods, carrot and garlic. Only egg
      white showed a lower content, 3nmol/g. Overall the content in chicken liver,
      chicken white meat, and egg yolk had a total content of vitamin B(6) between 42
      and 51nmol/g. Both PM and PMP were high in the chicken liver. In contrast, PL and
      PLP were high in the chicken white meat. The main vitamin B(6) in the egg yolk
      was PLP. The dried anchovy contained high amounts of PLP and PMP and a total
      content of 144nmol/g. CONCLUSIONS: The enzymatic-based HPLC method was applied
      for the determination of seven vitamin B6 compounds in foods. Their distribution
      in the foods varied significantly.

PMID- 22481896
TI  - Vitamin food fortification today.
AB  - Historically, food fortification has served as a tool to address population-wide
      nutrient deficiencies such as rickets by vitamin D fortified milk. This article
      discusses the different policy strategies to be used today. Mandatory or
      voluntary fortification and fortified foods, which the consumer needs, also have
      to comply with nutritional, regulatory, food safety and technical issues. The
      'worldwide map of vitamin fortification' is analysed, including differences
      between develop and developing countries. The vitamins, folate and vitamin D, are
      taken as practical examples in the review of the beneficial effect of different
      strategies on public health. The importance of the risk-benefit aspect, as well
      as how to identify the risk groups, and the food vehicles for fortification is
      discussed.

PMID- 22481898
TI  - Dietary intake of menaquinone-4 may determine hepatic and pancreatic menaquinone
      4 in chickens.
AB  - OBJECTIVE: The aim of this study was to determine the biological effects of
      natural dietary intake of vitamin K as phylloquinone (K(1)) and menaquinone-4 (MK
      4) and a control diet also containing menadione (K(3)) on levels of K(1) and
      total MK-4 (menaquinone-4) and menaquinone-4-2,3-epoxide (MK-4O)) in liver and
      pancreas, and on femur bending resistance in a fast-growing animal model. DESIGN:
      Chickens were fed four wheat-based diets from day 11 to day 22 after hatching.
      The diets contained different combinations of fat sources: rapeseed oil, animal
      rendered fat, soybean oil and hydrogenated soybean oil. Concentration of K(1) in
      the three experimental diets was 120 ng/g whereas MK-4 levels were 23, 52 and 63
      ng/g respectively. The control diet contained 157 ng K(1)/g, 75 ng MK-4/g and
      2.250 ng K(3)/g. RESULTS: Growth rates and femur strength confirmed adequate
      supply of nutrients and vitamin K in the test groups. There were no significant
      differences in femur bending resistance among the test groups, but these were
      higher than the control. K(1), MK-4 and MK-4O were found in liver. In pancreas,
      mainly MK-4O was found with small amounts of MK-4, but none had content of K(1).
      In the test groups the hepatic levels of MK-4 and MK-4O reflected the dietary
      intake of MK-4. CONCLUSION: The chickens were in good health with good bone
      resistance without supplements of K(3) in the feed, but at least a natural
      content of 23 ng MK-4/g feed. Liver and pancreas appears to use MK-4 in different
      ways.

PMID- 22481899
TI  - Evaluation of the Dutch general exemption level for voluntary fortification with
      folic acid.
AB  - INTRODUCTION: Fortification with folic acid was prohibited in the Netherlands.
      Since 2007, a general exemption is given to fortify with folic acid up until a
      maximum level of 100 ug/100 kcal. This maximum level was based on a calculation
      model and data of adults only. The model requires parameters on intake (diet,
      supplements, energy) and on the proportion of energy that may be fortified. This
      study aimed to evaluate the model parameters considering the changing
      fortification market. In addition, the risk of young children exceeding the UL
      for folic acid was studied. METHODS: Folic acid fortified foods present on the
      Dutch market were identified in product databases and by a supermarket inventory.
      Together with data of the Dutch National Consumption Survey-Young Children
      (2005/2006) these inventory results were used to re-estimate the model
      parameters. Habitual folic acid intake of young children was estimated and
      compared to the UL for several realistic fortification scenarios. RESULTS: Folic
      acid fortified foods were identified in seven different food groups. In up to 10%
      of the population, the proportion of energy intake of folic acid fortified foods
      exceeded 10% - the original model parameter. The folic acid intake from food
      supplements was about 100 ug/day, which is lower than the intake assumed as the
      original model parameter (300 ug). In the scenarios representing the current
      market situation, a small proportion (<5%) of the children exceeded the UL.
      CONCLUSION: The maximum fortification level of 100 ug/100 kcal is sufficiently
      protective for children in the current market situation. In the precautionary
      model to estimate the maximum fortification levels, subjects with high intakes of
      folic acid from food and supplements, and high energy intakes are protected from
      too high folic acid intakes. Combinations of high intakes are low in this
      population. The maximum levels should be monitored and revised with increasing
      fortification and supplementation practices.

PMID- 22481900
TI  - Updated folate data in the Dutch Food Composition Database and implications for
      intake estimates.
AB  - BACKGROUND AND OBJECTIVE: Nutrient values are influenced by the analytical method
      used. Food folate measured by high performance liquid chromatography (HPLC) or by
      microbiological assay (MA) yield different results, with in general higher
      results from MA than from HPLC. This leads to the question of how to deal with
      different analytical methods in compiling standardised and internationally
      comparable food composition databases? A recent inventory on folate in European
      food composition databases indicated that currently MA is more widely used than
      HPCL. Since older Dutch values are produced by HPLC and newer values by MA,
      analytical methods and procedures for compiling folate data in the Dutch Food
      Composition Database (NEVO) were reconsidered and folate values were updated.
      This article describes the impact of this revision of folate values in the NEVO
      database as well as the expected impact on the folate intake assessment in the
      Dutch National Food Consumption Survey (DNFCS). DESIGN: The folate values were
      revised by replacing HPLC with MA values from recent Dutch analyses. Previously
      MA folate values taken from foreign food composition tables had been recalculated
      to the HPLC level, assuming a 27% lower value from HPLC analyses. These
      recalculated values were replaced by the original MA values. Dutch HPLC and MA
      values were compared to each other. Folate intake was assessed for a subgroup
      within the DNFCS to estimate the impact of the update. RESULTS: In the updated
      NEVO database nearly all folate values were produced by MA or derived from MA
      values which resulted in an average increase of 24%. The median habitual folate
      intake in young children was increased by 11-15% using the updated folate values.
      CONCLUSION: The current approach for folate in NEVO resulted in more transparency
      in data production and documentation and higher comparability among European
      databases. Results of food consumption surveys are expected to show higher folate
      intakes when using the updated values.

PMID- 22481901
TI  - Parallel computation in medical imaging applications.

PMID- 22481902
TI  - Machine learning in medical imaging.

PMID- 22481903
TI  - Adaptive noise reduction of scintigrams with a wavelet transform.
AB  - The aim of this study was to eliminate the effect of Poisson noise in scintigrams
      with a wavelet thresholding method. We developed a new noise reduction method
      with a wavelet transform. The proposed method was a combination of the
      translation-invariant denoising method and our newly introduced denoising filter
      which was applicable for Poisson noise. To evaluate the validity of our proposed
      method, phantom images and scintigrams were used. The results with the phantom
      images showed that our method was better than conventional methods in terms of
      the peak signal-to-noise ratio by 3 dB. Quality of the scintigrams processed with
      our method was better than that with the conventional methods in terms of
      reducing Poisson noise while preserving edge components. The results demonstrated
      that the proposed method was effective for the reduction of Poisson noise in
      scintigrams.

PMID- 22481904
TI  - Measurement and Analysis of Microwave Frequency Signals Transmitted through the
      Breast.
AB  - Microwave approaches to breast imaging include the measurement of signals
      transmitted through and reflected from the breast. Prototype systems typically
      feature sensors separated from the breast, resulting in measurements that include
      the effects of the environment and system. To gain insight into transmission of
      microwave signals through the breast, a system that places sensors in direct
      contact with the breast is proposed. The system also includes a lossy immersion
      medium that enables measurement of the signal passing through the breast while
      significantly attenuating signals traveling along other paths. Collecting
      measurements at different separations between sensors also provides the
      opportunity to estimate the average electrical properties of the breast tissues.
      After validation through simulations and measurements, a study of 10 volunteers
      was performed. Results indicate symmetry between the right and left breast and
      demonstrate differences in attenuation, maximum frequency for reliable
      measurement, and average properties that likely relate to variations in breast
      composition.

PMID- 22481905
TI  - Detection and quantification of fluorescent cell clusters in cryo-imaging.
AB  - We developed and evaluated an algorithm for enumerating fluorescently labeled
      cells (e.g., stem and cancer cells) in mouse-sized, microscopic-resolution, cryo
      image volumes. Fluorescent cell clusters were detected, segmented, and then fit
      with a model which incorporated a priori information about cell size, shape, and
      intensity. The robust algorithm performed well in phantom and tissue imaging
      tests, including accurate (<2% error) counting of cells in mouse. Preliminary
      experiments demonstrate that cryo-imaging and software can uniquely analyze
      delivery, homing to an organ and tissue distribution of stem cell therapeutics.

PMID- 22481906
TI  - Microwave breast imaging system prototype with integrated numerical
      characterization.
AB  - The increasing number of experimental microwave breast imaging systems and the
      need to properly model them have motivated our development of an integrated
      numerical characterization technique. We use Ansoft HFSS and a formalism we
      developed previously to numerically characterize an S-parameter- based breast
      imaging system and link it to an inverse scattering algorithm. We show successful
      reconstructions of simple test objects using synthetic and experimental data. We
      demonstrate the sensitivity of image reconstructions to knowledge of the
      background dielectric properties and show the limits of the current model.

PMID- 22481908
TI  - Real-Time Compressive Sensing MRI Reconstruction Using GPU Computing and Split
      Bregman Methods.
AB  - Compressive sensing (CS) has been shown to enable dramatic acceleration of MRI
      acquisition in some applications. Being an iterative reconstruction technique, CS
      MRI reconstructions can be more time-consuming than traditional inverse Fourier
      reconstruction. We have accelerated our CS MRI reconstruction by factors of up to
      27 by using a split Bregman solver combined with a graphics processing unit (GPU)
      computing platform. The increases in speed we find are similar to those we
      measure for matrix multiplication on this platform, suggesting that the split
      Bregman methods parallelize efficiently. We demonstrate that the combination of
      the rapid convergence of the split Bregman algorithm and the massively parallel
      strategy of GPU computing can enable real-time CS reconstruction of even
      acquisition data matrices of dimension 4096(2) or more, depending on available
      GPU VRAM. Reconstruction of two-dimensional data matrices of dimension 1024(2)
      and smaller took ~0.3 s or less, showing that this platform also provides very
      fast iterative reconstruction for small-to-moderate size images.

PMID- 22481907
TI  - Pixel-based machine learning in medical imaging.
AB  - Machine learning (ML) plays an important role in the medical imaging field,
      including medical image analysis and computer-aided diagnosis, because objects
      such as lesions and organs may not be represented accurately by a simple
      equation; thus, medical pattern recognition essentially require "learning from
      examples." One of the most popular uses of ML is classification of objects such
      as lesions into certain classes (e.g., abnormal or normal, or lesions or
      nonlesions) based on input features (e.g., contrast and circularity) obtained
      from segmented object candidates. Recently, pixel/voxel-based ML (PML) emerged in
      medical image processing/analysis, which use pixel/voxel values in images
      directly instead of features calculated from segmented objects as input
      information; thus, feature calculation or segmentation is not required. Because
      the PML can avoid errors caused by inaccurate feature calculation and
      segmentation which often occur for subtle or complex objects, the performance of
      the PML can potentially be higher for such objects than that of common
      classifiers (i.e., feature-based MLs). In this paper, PMLs are surveyed to make
      clear (a) classes of PMLs, (b) similarities and differences within (among)
      different PMLs and those between PMLs and feature-based MLs, (c) advantages and
      limitations of PMLs, and (d) their applications in medical imaging.

PMID- 22481909
TI  - Cortical Surface Reconstruction from High-Resolution MR Brain Images.
AB  - Reconstruction of the cerebral cortex from magnetic resonance (MR) images is an
      important step in quantitative analysis of the human brain structure, for
      example, in sulcal morphometry and in studies of cortical thickness. Existing
      cortical reconstruction approaches are typically optimized for standard
      resolution (~1 mm) data and are not directly applicable to higher resolution
      images. A new PDE-based method is presented for the automated cortical
      reconstruction that is computationally efficient and scales well with grid
      resolution, and thus is particularly suitable for high-resolution MR images with
      submillimeter voxel size. The method uses a mathematical model of a field in an
      inhomogeneous dielectric. This field mapping, similarly to a Laplacian mapping,
      has nice laminar properties in the cortical layer, and helps to identify the
      unresolved boundaries between cortical banks in narrow sulci. The pial cortical
      surface is reconstructed by advection along the field gradient as a geometric
      deformable model constrained by topology-preserving level set approach. The
      method's performance is illustrated on exvivo images with 0.25-0.35 mm isotropic
      voxels. The method is further evaluated by cross-comparison with results of the
      FreeSurfer software on standard resolution data sets from the OASIS database
      featuring pairs of repeated scans for 20 healthy young subjects.

PMID- 22481910
TI  - Semiautomated multimodal breast image registration.
AB  - Consideration of information from multiple modalities has been shown to have
      increased diagnostic power in breast imaging. As a result, new techniques such as
      microwave imaging continue to be developed. Interpreting these novel image
      modalities is a challenge, requiring comparison to established techniques such as
      the gold standard X-ray mammography. However, due to the highly deformable nature
      of breast tissues, comparison of 3D and 2D modalities is a challenge. To enable
      this comparison, a registration technique was developed to map features from 2D
      mammograms to locations in the 3D image space. This technique was developed and
      tested using magnetic resonance (MR) images as a reference 3D modality, as MR
      breast imaging is an established technique in clinical practice. The algorithm
      was validated using a numerical phantom then successfully tested on twenty-four
      image pairs. Dice's coefficient was used to measure the external goodness of fit,
      resulting in an excellent overall average of 0.94. Internal agreement was
      evaluated by examining internal features in consultation with a radiologist, and
      subjective assessment concludes that reasonable alignment was achieved.

PMID- 22481911
TI  - Towards improved collagen assessment: polarization-sensitive optical coherence
      tomography with tailored reference arm polarization.
AB  - Single channel PS-OCT has advantages for assessing birefringent tissue components
      in various clinical scenarios, with implications for assessing pathology, ranging
      from osteoarthritis to myocardial infarction. While the technique has been
      successfully used both in vitro and in vivo, there have been limited attempts to
      optimize single channel PS-OCT with respect to performance, particularly paddle
      rotation. In this study, we developed and tested a new approach for the real-time
      assessment of birefringence through tailoring of reference arm polarization.
      Different polarization rotation patterns, as depicted on a Poincare sphere, were
      assessed with polarization filters and retarders. When further tested in tissue,
      PS-OCT assessments of bovine cartilage and tendon demonstrated that contrast was
      sensitive to the pattern selected, indicating that rotation pattern influenced
      birefringence assessment and providing insights into optimal patterns. We also
      discuss the difference between diagnostic accuracy and precision with respect to
      both the construction and application of PS-OCT embodiments.

PMID- 22481912
TI  - FDK-Type Algorithms with No Backprojection Weight for Circular and Helical Scan
      CT.
AB  - We develop two Feldkamp-type reconstruction algorithms with no backprojection
      weight for circular and helical trajectory with planar detector geometry.
      Advances in solid-state electronic detector technologies lend importance to CT
      systems with the equispaced linear array, the planar (flat panel) detectors, and
      the corresponding algorithms. We derive two exact Hilbert filtered backprojection
      (FBP) reconstruction algorithms with no backprojection weight for 2D fan-beam
      equispace linear array detector geometry (complement of the equi-angular curved
      array detector). Based on these algorithms, the Feldkamp-type algorithms with no
      backprojection weight for 3D reconstruction are developed using the standard
      heuristic extension of the divergent beam FBP algorithm. The simulation results
      show that the axial intensity drop in the reconstructed image using the FDK
      algorithms with no backprojection weight with circular trajectory is similar to
      that obtained by using Hu's and T-FDK, algorithms. Further, we present efficient
      algorithms to reduce the axial intensity drop encountered in the standard FDK
      reconstructions in circular cone-beam CT. The proposed algorithms consist of
      mainly two steps: reconstruction of the object using FDK algorithm with no
      backprojection weight and estimation of the missing term. The efficient
      algorithms are compared with the FDK algorithm, Hu's algorithm, T-FDK, and Zhu et
      al.'s algorithm in terms of axial intensity drop and noise. Simulation shows that
      the efficient algorithms give similar performance in axial intensity drop as that
      of Zhu et al.'s algorithm while one of the efficient algorithms outperforms Zhu
      et al.'s algorithm in terms of computational complexity.

PMID- 22481913
TI  - PPARgamma and Oxidative Stress: Con(beta) Catenating NRF2 and FOXO.
AB  - Peroxisome-proliferator activator receptor gamma (PPARgamma) is a nuclear
      receptor of central importance in energy homeostasis and inflammation. Recent
      experimental pieces of evidence demonstrate that PPARgamma is implicated in the
      oxidative stress response, an imbalance between antithetic prooxidation and
      antioxidation forces that may lead the cell to apoptotic or necrotic death. In
      this delicate and intricate game of equilibrium, PPARgamma stands out as a
      central player devoted to the quenching and containment of the damage and to
      foster cell survival. However, PPARgamma does not act alone: indeed the nuclear
      receptor is at the point of interconnection of various pathways, such as the
      nuclear factor erythroid 2-related factor 2 (NRF2), Wnt/beta-catenin, and
      forkhead box proteins O (FOXO) pathways. Here we reviewed the role of PPARgamma
      in response to oxidative stress and its interaction with other signaling pathways
      implicated in this process, an interaction that emerged as a potential new
      therapeutic target for several oxidative-related diseases.

PMID- 22481914
TI  - New insights into the role of peroxisome proliferator-activated receptors in
      regulating the inflammatory response after tissue injury.
AB  - Major trauma results in a strong inflammatory response in injured tissue. This
      posttraumatic hyperinflammation has been implied in the adverse events leading to
      a breakdown of host defense mechanisms and ultimately to delayed organ failure.
      Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been
      identified as potent modulators of inflammation in various acute and chronic
      inflammatory conditions. The main mechanism of action mediated by ligand binding
      to PPARs is the inhibition of the nuclear transcription factor NF-kappaB, leading
      to downregulation of downstream gene transcription, such as for genes encoding
      proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti
      inflammatory properties in various animal models of tissue injury, including
      central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In
      addition, PPAR agonists have been shown to induce wound healing process after
      tissue trauma. The present review was designed to provide an up-to-date overview
      on the current understanding of the role of PPARs in the pathophysiology of the
      inflammatory response after major trauma. Therapeutic options for using
      recombinant PPAR agonists as pharmacological agents in the management of
      posttraumatic inflammation will be discussed.

PMID- 22481915
TI  - beta-Secretases, Alzheimer's Disease, and Down Syndrome.
AB  - Individuals with Down Syndrome (DS), or trisomy 21, develop Alzheimer's disease
      (AD) pathology by approximately 40 years of age. Chromosome 21 harbors several
      genes implicated in AD, including the amyloid precursor protein and one homologue
      of the beta-site APP cleaving enzyme, BACE2. Processing of the amyloid precursor
      protein by beta-secretase (BACE) is the rate-limiting step in the production of
      the pathogenic Abeta peptide. Increased amounts of APP in the DS brain result in
      increased amounts of Abeta and extracellular plaque formation beginning early in
      life. BACE dysregulation potentially represents an overlapping biological
      mechanism with sporadic AD and a common therapeutic target. As the lifespan for
      those with DS continues to increase, age-related concerns such as obesity,
      depression, and AD are of growing concern. The ability to prevent or delay the
      progression of neurodegenerative diseases will promote healthy aging and improve
      quality of life for those with DS.

PMID- 22481916
TI  - Toll-like receptor 7 agonist therapy with imidazoquinoline enhances cancer cell
      death and increases lymphocytic infiltration and proinflammatory cytokine
      production in established tumors of a renal cell carcinoma mouse model.
AB  - Imidazoquinolines are synthetic toll-like receptor 7 and 8 agonists and potent
      dendritic cell activators with established anticancer activity. Here we test the
      hypothesis that imidazoquinoline has in vivo efficacy within established renal
      cell carcinoma (RCC) tumors. Immunocompetent mice bearing syngeneic RCC
      xenografts were treated with imidazoquinoline or placebo at two separate time
      points. Harvested tumors were assayed by TUNEL/caspase-3/Ki67 immunostains to
      evaluate cell death/apoptosis/proliferation, and CD3/B220/CD45 immunostains to
      evaluate T-cell lymphocyte/B-cell lymphocyte/pan-leukocyte tumor infiltration.
      ELISA measurement of tumor and serum levels of proinflammatory cytokines, IL-6
      and MCP-1, was performed. A single imidazoquinoline dose significantly decreased
      RCC tumor growth by 50% and repeat dosing compounded the effect, without observed
      weight loss or other toxicity. Tumor immunostaining revealed significant
      increases in cell death and apoptosis without changes in cell proliferation,
      supporting induction of apoptosis as the primary mechanism of tumor growth
      suppression. Imidazoquinoline treatment also significantly enhanced peritumoral
      aggregation and intratumoral infiltration by T-cell lymphocytes, while increasing
      intratumoral (but not serum) levels of proinflammatory cytokines. In conclusion,
      imidazoquinoline treatment enhances T-cell lymphocyte infiltration and
      proinflammatory cytokine production within established mouse RCC tumors, while
      suppressing tumor growth via induction of cancer cell apoptosis. These findings
      support a therapeutic role for imidazoquinoline in RCC.

PMID- 22481917
TI  - Hepatic arterial therapy with drug-eluting beads in the management of metastatic
      pancreatic carcinoma to the liver: a multi-institutional registry.
AB  - Introduction. There has been limited reporting on the use of hepatic-directed
      therapy in liver dominant hepatic metastases arising from pancreatic cancer.
      Methods. An IRB-approved prospective multi-institutional treatment registry of
      885 patients undergoing 1458 treatments for primary or secondary cancers in the
      liver was evaluated from January 2007 to January 2011. Results. Ten patients
      underwent a total of 17 treatment sessions with drug-eluting beads (DEBs). Six
      patients received concurrent chemotherapy while undergoing DEB with no severe
      adverse events. After a median followup of 16 months, the 6- and 12-month
      response rates were 80% and 75%, respectively, with a median overall survival of
      9.3 months. Conclusion. Hepatic arterial therapy with DEB can be safely and
      effectively used in selected patients with liver predominant metastatic disease
      from pancreatic cancer. This therapy should be considered in combination with
      systemic chemotherapy as a possible second therapy given the limited response
      rates of second-line chemotherapy.

PMID- 22481920
TI  - Hepatic arterial therapy with drug-eluting beads in the management of metastatic
      bronchogenic carcinoma to the liver: a multi-institutional registry.
AB  - Introduction. There has been limited information reported on the use of hepatic
      arterial therapy in liver dominant hepatic metastases arising from lung cancer.
      The aim of this study was to evaluate the safety and efficacy of hepatic arterial
      therapy in the treatment of liver dominant hepatic metastases arising from lung
      cancer. Methods. Thirteen patients underwent a total of 30 treatment sessions
      with Drug-Eluting Beads. Eight of the thirteen received only doxorubicin DEB (17
      of the total treatments), and four patients received Irinotecan DEB (7 of the
      total treatments). Results. The planned preprocedural dosage was a median of 75
      mg (range 19-200), with total hepatic dose exposure being a median of 150 mg
      (range 0-458), with a technical success rate of 97% in all 29 treatments. There
      were 4 adverse events related to treatment, but no evidence of hepatic
      insufficiency. Overall 6-month and 12-month response rates were 50%. After a
      median followup of 24 months, the median overall survival in this cohort was 14
      months (range 7-48 months). Conclusion. Drug-eluting beads loaded with
      doxorubicin (DEBDOX) or irinotecan (DEBIRI) can be safely and effectively used in
      treatment of patients with liver predominant metastatic disease from lung cancer.

PMID- 22481919
TI  - Role of protein biomarkers in the detection of high-grade disease in cervical
      cancer screening programs.
AB  - Since the Pap test was introduced in the 1940s, there has been an approximately
      70% reduction in the incidence of squamous cell cervical cancers in many
      developed countries by the application of organized and opportunistic screening
      programs. The efficacy of the Pap test, however, is hampered by high
      interobserver variability and high false-negative and false-positive rates. The
      use of biomarkers has demonstrated the ability to overcome these issues, leading
      to improved positive predictive value of cervical screening results. In addition,
      the introduction of HPV primary screening programs will necessitate the use of a
      follow-up test with high specificity to triage the high number of HPV-positive
      tests. This paper will focus on protein biomarkers currently available for use in
      cervical cancer screening, which appear to improve the detection of women at
      greatest risk for developing cervical cancer, including Ki-67, p16(INK4a), BD
      ProEx C, and Cytoactiv HPV L1.

PMID- 22481918
TI  - Tumor lymphangiogenesis as a potential therapeutic target.
AB  - Metastasis the spread of cancer cells to distant organs, is the main cause of
      death for cancer patients. Metastasis is often mediated by lymphatic vessels that
      invade the primary tumor, and an early sign of metastasis is the presence of
      cancer cells in the regional lymph node (the first lymph node colonized by
      metastasizing cancer cells from a primary tumor). Understanding the interplay
      between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels
      associated with tumor growth) will provide us with new insights into mechanisms
      that modulate metastatic spread. In the long term, these insights will help to
      define new molecular targets that could be used to block lymphatic vessel
      mediated metastasis and increase patient survival. Here, we review the molecular
      mechanisms of embryonic lymphangiogenesis and those that are recapitulated in
      tumor lymphangiogenesis, with a view to identifying potential targets for
      therapies designed to suppress tumor lymphangiogenesis and hence metastasis.

PMID- 22481921
TI  - A proposal of a practical and optimal prophylactic strategy for peritoneal
      recurrence.
AB  - Peritoneal metastasis, which often arises in patients with advanced gastric
      cancer, is well known as a miserable and ill-fated disease. Once peritoneal
      metastasis is formed, it is extremely difficult to defeat. We advocated EIPL
      (extensive intraoperative peritoneal lavage) as a useful and practical adjuvant
      surgical technique for those gastric cancer patients who are likely to suffer
      from peritoneal recurrence. In this paper, we review the effect of EIPL therapy
      on prevention of peritoneal recurrence on patients with peritoneal free cancer
      cells without overt peritoneal metastasis (CY+/P-) through the prospective
      randomized study, and we verified its potential as an optimal and standard
      prophylactic therapeutic strategy for peritoneal recurrence.

PMID- 22481922
TI  - Regulatory T cells in human ovarian cancer.
AB  - Multiple layers of suppressive components including regulatory T (T(Reg)) cells,
      suppressive antigen-presenting cells, and inhibitory cytokines form suppressive
      networks in the ovarian cancer microenvironment. It has been demonstrated that as
      a major suppressive element, T(Reg) cells infiltrate tumor, interact with several
      types of immune cells, and mediate immune suppression through different molecular
      and cellular mechanisms. In this paper, we focus on human ovarian cancer and will
      discuss the nature of T(Reg) cells including their subsets, trafficking,
      expansion, and function. We will briefly review the development of manipulation
      of T(Reg) cells in preclinical and clinical settings.

PMID- 22481924
TI  - Cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative
      chemotherapy in the treatment of advanced epithelial ovarian cancer.
AB  - Background/Aims. Intraperitoneal intraoperative hyperthermic chemotherapy (HIPEC)
      has been used in the treatment of ovarian cancer. The purpose of the study is to
      determine the efficacy of HIPEC after cytoreductive surgery in advanced ovarian
      cancer. Patients/Methods. From 2006 to 2010 patients with advanced ovarian cancer
      were enrolled in a prospective nonrandomized study to undergo cytoreductive
      surgery combined with HIPEC. Clinical and histopathological variables were
      correlated to hospital mortality, morbidity, survival, and recurrences. Results.
      The mean age of 43 women was 59.9 +/- 13.8 (16-82) years. The hospital mortality
      and morbidity rate were 4.7% and 51.2%, respectively. Complete cytoreduction was
      possible in 69.8%. The overall 5-year survival rate was 54%. The prognostic
      indicators of survival were the extent of prior surgery (P = 0.048) and the
      extent of peritoneal dissemination (P = 0.011). The recurrence rate was 30.2%.
      Conclusions. Maximal cytoreductive surgery combined with HIPEC is a well
      tolerated, feasible, and promising method of treatment in advanced ovarian
      cancer.

PMID- 22481923
TI  - Matricellular proteins: a sticky affair with cancers.
AB  - The multistep process of metastasis is a major hallmark of cancer progression
      involving the cointeraction and coevolution of the tumor and its
      microenvironment. In the tumor microenvironment, tumor cells and the surrounding
      stromal cells aberrantly secrete matricellular proteins, which are a family of
      nonstructural proteins in the extracellular matrix (ECM) that exert regulatory
      roles via a variety of molecular mechanisms. Matricellular proteins provide
      signals that support tumorigenic activities characteristic of the metastastic
      cascade such as epithelial-to-mesenchymal (EMT) transition, angiogenesis, tumor
      cell motility, proliferation, invasion, evasion from immune surveillance, and
      survival of anoikis. Herein, we review the current understanding of the following
      matricellular proteins and highlight their pivotal and multifacted roles in
      metastatic progression: angiopoietin-like protein 4 (ANGPTL4), CCN family members
      cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) and CCN6, osteopontin (OPN),
      secreted protein acidic and rich in cysteine (SPARC), tenascin C (TNC), and
      thrombospondin-1 and -2 (TSP1, TSP2). Insights into the signaling mechanisms
      resulting from the interaction of these matricellular proteins and their
      respective molecular partner(s), as well as their subsequent contribution to
      tumor metastasis, are discussed. In addition, emerging evidences of their
      promising potential as therapeutic options and/or targets in the treatment of
      cancer are also highlighted.

PMID- 22481925
TI  - Molecular Analysis of TTF-1 and TTF-2 Genes in Patients with Early Onset
      Papillary Thyroid Carcinoma.
AB  - Two common variants, close from TTF-1 and TTF-2, were shown to predispose to
      thyroid cancer (TC) in European populations. We aimed to investigate whether TTF
      1 and TTF-2 variants might contribute to TC early onset (EO). Tumor samples from
      eighteen patients with papillary TC (PTC), who underwent total thyroidectomy at
      an age of <=21, were screened for TTF-1 and TTF-2 variants. No TTF-1 variants
      were documented; two novel germinal TTF-2 variants, c.200C>G (p.A67G) and
      c.510C>A (p.A170A), were identified in two patients. Two already described TTF-2
      variants were also documented; the allelic frequency among patients was not
      different from that observed among controls. Moreover, RET/PTC rearrangements and
      the BRAFV600E mutation were identified in 5/18 and 2/18 PTCs, respectively.
      Thyroglobulin (TG) and thyroid peroxidase (TPO) expression was found to be
      significantly decreased in tumors, and the lowest level of TPO expression
      occurred in a tumor harboring both the p.A67GTTF-2 variant and a RET/PTC3
      rearrangement.

PMID- 22481926
TI  - Special Agents Hunting Down Women Silent Killer: The Emerging Role of the
      p38alpha Kinase.
AB  - Ovarian cancer is sensitive to chemotherapy with platinum compounds; however, the
      therapy success rate is significantly lowered by a high incidence of recurrence
      and by the acquisition of drug resistance. These negative outcomes mainly depend
      on altered apoptotic and drug resistance pathways, determining the need for the
      design of new therapeutic strategies to improve patient survival. This challenge
      has become even more critical because it has been recognized that hindering
      uncontrolled cell growth is not sufficient as the only curative approach. In
      fact, while current therapies are mostly conceived to impair survival of highly
      proliferating cells, several lines of research are now focusing on cancer
      specific features to specifically target malignant cells with the aim of avoiding
      drug resistance and reducing adverse effects. Recently, great interest has been
      generated by the identification of metabolic reprogramming mechanisms occurring
      in cancer cells, such as the increase in glycolysis levels. In this light,
      pharmacologic manipulation of relevant pathways involved in cancer-specific
      metabolism and drug resistance could prove an effective approach to treat ovarian
      cancer patients.

PMID- 22481928
TI  - Papillomavirus from the bench to the clinics.

PMID- 22481927
TI  - Immunotherapy of genitourinary malignancies.
AB  - Most cancer patients are treated with some combination of surgery, radiation, and
      chemotherapy. Despite recent advances in local therapy with curative intent,
      chemotherapeutic treatments for metastatic disease often remain unsatisfying due
      to severe side effects and incomplete long-term remission. Therefore, the
      evaluation of novel therapeutic options is of great interest. Conventional, along
      with newer treatment strategies target the immune system that suppresses
      genitourinary (GU) malignancies. Metastatic renal cell carcinoma and non-muscle
      invasive bladder caner represent the most immune-responsive types of all human
      cancer. This review examines the rationale and emerging evidence supporting the
      anticancer activity of immunotherapy, against GU malignancies.

PMID- 22481929
TI  - GRP78 Protein Expression in Ovarian Cancer Patients and Perspectives for a Drug
      Targeting Approach.
AB  - Glucose-regulated protein of 78 kD (GRP78) is a chaperone protein mainly located
      in the endoplasmic reticulum (ER). This protein is normally present at low levels
      in adult cells but its expression is triggered by ER stress including glucose
      deprivation and hypoxia. In tumor cells, it is overexpressed with fraction of
      protein found at the cell surface. This paper presents the physiology of GRP78 in
      the context of ovarian cancer and its potential use as drug delivery systems
      targeting ovarian cancer cell.

PMID- 22481930
TI  - Lm-LLO-Based Immunotherapies and HPV-Associated Disease.
AB  - HPV infection is a direct cause of neoplasia and malignancy. Cellular immunologic
      activity against cells expressing HPV E6 and E7 is sufficient to eliminate the
      presence of dysplastic or neoplastic tissue driven by HPV infection. Live
      attenuated Listeria monocytogenes- (Lm-) based immunotherapy (ADXS11-001) has
      been developed for the treatment of HPV-associated diseases. ADXS11-001 secretes
      an antigen-adjuvant fusion (Lm-LLO) protein consisting of a truncated fragment of
      the Lm protein listeriolysin O (LLO) fused to HPV-16 E7. In preclinical models,
      this construct has been found to stimulate immune responses and affect
      therapeutic outcome. ADXS11-001 is currently being evaluated in Phase 2 clinical
      trials for cervical intraepithelial neoplasia, cervical cancer, and HPV-positive
      head and neck cancer. The use of a live attenuated bacterium is a more complex
      and complete method of cancer immunotherapy, as over millennia Lm has evolved to
      infect humans and humans have evolved to prevent and reject this infection over
      millennia. This evolution has resulted in profound pathogen-associated immune
      mechanisms which are genetically conserved, highly efficacious, resistant to
      tolerance, and can be uniquely invoked using this novel platform technology.

PMID- 22481931
TI  - The molecular biology of brain metastasis.
AB  - Metastasis to the central nervous system (CNS) remains a major cause of morbidity
      and mortality in patients with systemic cancers. Various crucial interactions
      between the brain environment and tumor cells take place during the development
      of the cancer at its new location. The rapid expansion in molecular biology and
      genetics has advanced our knowledge of the underlying mechanisms involved, from
      invasion to final colonization of new organ tissues. Understanding the various
      events occurring at each stage should enable targeted drug delivery and
      individualized treatments for patients, with better outcomes and fewer side
      effects. This paper summarizes the principal molecular and genetic mechanisms
      that underlie the development of brain metastasis (BrM).

PMID- 22481933
TI  - Clinical significance of langerhans cells in squamous cell carcinoma of the
      larynx.
AB  - Langerhans cells (LCs) may be involved in the immunosurveillance against tumors
      as antigen-presenting cells. Our objective has been to determine the relevance of
      LC in progression of larynx squamous cell carcinomas and their relationship with
      different subpopulations of tumor-infiltrating cells. LCs were investigated by
      immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of
      the primary tumors studied (44 out of 50) and also in metastases (6 out of 10)
      and recurrences (2 out of 3), but we did not find any statistical association
      between number of LCs and clinical-pathological parameters or survival. However,
      the number of LCs was increased in patients with evident infiltration of
      lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not
      show clinical utility as prognostic marker, they may play a role in releasing an
      active immune response in larynx carcinomas, according to their ability to
      present antigens to sensitized T cells.

PMID- 22481934
TI  - An observational study of the first experience with bevacizumab for the treatment
      of patients with recurrent high-grade glioma in two belgian university hospitals.
AB  - Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody
      that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas
      (HGG) in phase II clinical trials. Patients and Methods. Data were collected from
      patients with recurrent HGG who initiated treatment with BEV outside a clinical
      trial protocol at two Belgian university hospitals. Results. 19 patients (11 M/8
      F) were administered a total of 138 cycles of BEV (median 4, range 1-31). Tumor
      response assessment by MRI was available for 15 patients; 2 complete responses
      and 3 partial responses for an objective response rate of 26% for the intent to
      treat population were observed on gadolinium-enhanced T1-weighted images;
      significant regressions on T2/FLAIR were documented in 10 out of 15 patients
      (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients.
      The six-month progression-free survival was 21% (95% CI 2.7-39.5). Two patients
      had an ongoing tumor response and remained free from progression after 12 months
      of BEV treatment. Conclusions. The activity and tolerability of BEV were
      comparable to results from previous prospective phase II trials. Reduced uptake
      on PET suggests a metabolic response in addition to an antiangiogenic effect in
      some cases with favorable clinical outcome.

PMID- 22481936
TI  - Modulation of C1-Inhibitor and Plasma Kallikrein Activities by Type IV Collagen.
AB  - The contact system of coagulation can be activated when in contact with
      biomaterials. As collagen is being tested in novel biomaterials in this study, we
      have investigated how type IV collagen affects plasma kallikrein and C1
      inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of
      0.86 MUM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and
      beta-factor XIIa activity and on C1-inhibitor function were determined. Factor
      XIIa rapidly lost activity in the presence of type IV collagen, whereas plasma
      kallikrein and beta-factor XIIa were more stable. The rate of inhibition of
      plasma kallikrein by C1-inhibitor was decreased by type IV collagen in a dose
      dependent manner. These studies could be relevant to the properties of
      biomaterials, which contain collagen, and should be considered in the testing for
      biocompatibility.

PMID- 22481937
TI  - Evaluation the effects of some relevant parameters on elastic modulus of pumpkin
      seed and its kernel.
AB  - The elastic modulus of two varieties of Iranian pumpkin seed and its kernel
      (namely, Zaria and Gaboor) were evaluated as a function of size (large, medium,
      and small), loading rate (2, 5, 8, and 10 mm/min), and moisture content (4, 7.8,
      14, and 20% d.b) under quasistatic compression loading. The results showed that
      elastic modulus of pumpkin seed and its kernel decreased with increasing moisture
      content and also increasing loading rate, for the varieties under study. The
      average modulus of elasticity of pumpkin seed from 68.86 to 46.65 Mpa and from
      97.14 to 74.93 Mpa was obtained for moisture levels ranging from 4 to 20%, for
      Zaria and Gaboor varieties, respectively. The elastic modulus of pumpkin seed
      decreased from 73.55 to 43.04 Mpa and from 101.83 to 71.32 Mpa with increasing
      loading rate from 2 to 10 mm/min for Zaria and Gaboor varieties, respectively.

PMID- 22481938
TI  - Evaluation of Antithrombogenicity and Hydrophilicity on Zein-SWCNT Electrospun
      Fibrous Nanocomposite Scaffolds.
AB  - Design of blood compatible surfaces is required to minimize platelet surface
      interactions and increase the thromboresistance of foreign surfaces when they are
      used as biomaterials especially for artificial blood prostheses. In this study,
      single wall carbon nanotubes (SWCNTs) and Zein fibrous nanocomposite scaffolds
      were fabricated by electrospinning and evaluated its antithrombogenicity and
      hydrophilicity. The uniform and highly smooth nanofibers of Zein composited with
      different SWCNTs content (ranging from 0.2 wt% to 1 wt%) were successfully
      prepared by electrospinning method without the occurrence of bead defects. The
      resulting fiber diameters were in the range of 100-300 nm without any beads.
      Composite nanofibers with and without SWCNT were characterized through a variety
      of methods including scanning electron microscopy, transmission electron
      microscopy, thermogravimetric analysis, and tensile mechanical testing. The water
      uptake and retention ability of composite scaffolds decreased whereas thermal
      stability increased with an addition of SWCNTs. Hemolytic property and platelet
      adhesion ability of the nanocomposite (Zein-SWCNTs) were explored. These
      observations suggest that the novel Zein-SWCNTs composite scaffolds may possibly
      hold great promises as useful antithrombotic material and promising biomaterials
      for tissue engineering application.

PMID- 22481932
TI  - Optimizing molecular-targeted therapies in ovarian cancer: the renewed surge of
      interest in ovarian cancer biomarkers and cell signaling pathways.
AB  - The hallmarks of ovarian cancer encompass the development of resistance, disease
      recurrence and poor prognosis. Ovarian cancer cells express gene signatures which
      pose significant challenges for cancer drug development, therapeutics, prevention
      and management. Despite enhancements in contemporary tumor debulking surgery,
      tentative combination regimens and abdominal radiation which can achieve
      beneficial response rates, the majority of ovarian cancer patients not only
      experience adverse effects, but also eventually relapse. Therefore, additional
      therapeutic possibilities need to be explored to minimize adverse events and
      prolong progression-free and overall response rates in ovarian cancer patients.
      Currently, a revival in cancer drug discovery is devoted to identifying
      diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and
      reliability of such biomarkers may be complicated by mutations in the BRCA1 or
      BRCA2 genes, diverse genetic risk factors, unidentified initiation and
      progression elements, molecular tumor heterogeneity and disease staging. There is
      thus a dire need to expand existing ovarian cancer therapies with broad-spectrum
      and individualized molecular targeted approaches. The aim of this review is to
      profile recent developments in our understanding of the interrelationships among
      selected ovarian tumor biomarkers, heterogeneous expression signatures and
      related molecular signal transduction pathways, and their translation into more
      efficacious targeted treatment rationales.

PMID- 22481935
TI  - Akt: a double-edged sword in cell proliferation and genome stability.
AB  - The Akt family of serine/threonine protein kinases are key regulators of multiple
      aspects of cell behaviour, including proliferation, survival, metabolism, and
      tumorigenesis. Growth-factor-activated Akt signalling promotes progression
      through normal, unperturbed cell cycles by acting on diverse downstream factors
      involved in controlling the G1/S and G2/M transitions. Remarkably, several recent
      studies have also implicated Akt in modulating DNA damage responses and genome
      stability. High Akt activity can suppress ATR/Chk1 signalling and homologous
      recombination repair (HRR) via direct phosphorylation of Chk1 or TopBP1 or,
      indirectly, by inhibiting recruitment of double-strand break (DSB) resection
      factors, such as RPA, Brca1, and Rad51, to sites of damage. Loss of checkpoint
      and/or HRR proficiency is therefore a potential cause of genomic instability in
      tumor cells with high Akt. Conversely, Akt is activated by DNA double-strand
      breaks (DSBs) in a DNA-PK- or ATM/ATR-dependent manner and in some circumstances
      can contribute to radioresistance by stimulating DNA repair by nonhomologous end
      joining (NHEJ). Akt therefore modifies both the response to and repair of
      genotoxic damage in complex ways that are likely to have important consequences
      for the therapy of tumors with deregulation of the PI3K-Akt-PTEN pathway.

PMID- 22481939
TI  - Oligonucleotide and Parylene Surface Coating of Polystyrene and ePTFE for
      Improved Endothelial Cell Attachment and Hemocompatibility.
AB  - In vivo self-endothelialization by endothelial cell adhesion on cardiovascular
      implants is highly desirable. DNA-oligonucleotides are an intriguing coating
      material with nonimmunogenic characteristics and the feasibility of easy and
      rapid chemical fabrication. The objective of this study was the creation of cell
      adhesive DNA-oligonucleotide coatings on vascular implant surfaces. DNA
      oligonucleotides immobilized by adsorption on parylene (poly(monoaminomethyl-para
      xylene)) coated polystyrene and ePTFE were resistant to high shear stress (9.5
      N/m(2)) and human blood serum for up to 96 h. Adhesion of murine endothelial
      progenitor cells, HUVECs and endothelial cells from human adult saphenous veins
      as well as viability over a period of 14 days of HUVECs on oligonucleotide coated
      samples under dynamic culture conditions was significantly enhanced (P < 0.05).
      Oligonucleotide-coated surfaces revealed low thrombogenicity and excellent
      hemocompatibility after incubation with human blood. These properties suggest the
      suitability of immobilization of DNA-oligonucleotides for biofunctionalization of
      blood vessel substitutes for improved in vivo endothelialization.

PMID- 22481940
TI  - Porous Hydroxyapatite and Aluminium-Oxide Ceramic Orbital Implant Evaluation
      Using CBCT Scanning: A Method for In Vivo Porous Structure Evaluation and
      Monitoring.
AB  - Objective. This study aimed to define CBCT as a technique for postimplantation in
      vivo examination of porous hydroxyapatite and aluminium-oxide orbital implant
      shape, volume and density changes. Methods and Materials. CBCT was used to
      evaluate 30 enucleated patients treated with spherical polyglactin 910 wrapped
      hydroxyapatite and aluminum-oxide orbital implants. The mean duration of patient
      followup was 3.2 years or 1338 days with a range of 0.2 to 7.2 years or 79 to
      2636 days in a population with an average age of 40.8 years. Results. The
      resolution of currently clinically used CBCT equipment allowed detailed
      structural observation of the orbital hydroxyapatite implants with some
      modifications. Volume and shape estimations were possible while density
      evaluation was more complicated compared to medical source computed tomography.
      The mean densities of the orbital implants were followed and a consistent gradual
      decrease identified from the beginning of implantation which was better defined
      after the applied correction procedure. Conclusion. CBCT with lower dosages of
      radiation exposure can be used to follow changes in implanted high-density porous
      structures. The density evaluation is possible with calibration modifications.
      Changes in orbital implant densities identified in this study may correspond to
      healing and maturation of soft tissues surrounding and penetrating the implants.

PMID- 22481941
TI  - Erythrocytes and erythropoietin.

PMID- 22481942
TI  - The Cytoplasm-to-Vacuole Targeting Pathway: A Historical Perspective.
AB  - From today's perspective, it is obvious that macroautophagy (hereafter autophagy)
      is an important pathway that is connected to a range of developmental and
      physiological processes. This viewpoint, however, is relatively recent,
      coinciding with the molecular identification of autophagy-related (Atg)
      components that function as the protein machinery that drives the dynamic
      membrane events of autophagy. It may be difficult, especially for scientists new
      to this area of research, to appreciate that the field of autophagy long existed
      as a "backwater" topic that attracted little interest or attention. Paralleling
      the development of the autophagy field was the identification and analysis of the
      cytoplasm-to-vacuole targeting (Cvt) pathway, the only characterized biosynthetic
      route that utilizes the Atg proteins. Here, we relate some of the initial
      history, including some never-before-revealed facts, of the analysis of the Cvt
      pathway and the convergence of those studies with autophagy.

PMID- 22481943
TI  - Identification and characterization of novel perivascular adventitial cells in
      the whole mount mesenteric branch artery using immunofluorescent staining and
      scanning confocal microscopy imaging.
AB  - A novel perivascular adventitial cell termed, adventitial neuronal somata
      (ANNIES) expressing the neural cell adhesion molecule (NCAM) and the vasodilator
      neuropeptide, calcitonin gene-related peptide (CGRP), exists in the adult rat
      mesenteric branch artery (MBA) in situ. In addition, we have previously shown
      that ANNIES coexpress CGRP and NCAM. We now show that ANNIES express the neurite
      growth marker, growth associated protein-43(Gap-43), palladin, and the calcium
      sensing receptor (CaSR), that senses changes in extracellular Ca(2+) and
      participates in vasodilator mechanisms. Thus, a previously characterized
      vasodilator, calcium sensing autocrine/paracrine system, exists in the
      perivascular adventitia associated with neural-vascular interface. Images of the
      whole mount MBA segments were analyzed under scanning confocal microscopy.
      Confocal analysis showed that the Gap-43, CaSR, and palladin were present in
      ANNIES about 37 +/- 4%, 94 +/- 6%, and 80 +/- 10% respectively, comparable to
      CGRP (100%). Immunoblots from MBA confirmed the presence of Gap-43 (48 kD), NCAM
      (120 and 140 kD), and palladin (90-92 and 140 kD). In summary, CGRP, and NCAM
      containing neural cells in the perivascular adventitia also express palladin and
      CaSR, and coexpress Gap-43 which may participate in response to stress/injury and
      vasodilator mechanisms as part of a perivascular sensory neural network.

PMID- 22481944
TI  - Reticulophagy and ribophagy: regulated degradation of protein production
      factories.
AB  - During autophagy, cytosol, protein aggregates, and organelles are sequestered
      into double-membrane vesicles called autophagosomes and delivered to the
      lysosome/vacuole for breakdown and recycling of their basic components. In all
      eukaryotes this pathway is important for adaptation to stress conditions such as
      nutrient deprivation, as well as to regulate intracellular homeostasis by
      adjusting organelle number and clearing damaged structures. For a long time,
      starvation-induced autophagy has been viewed as a nonselective transport pathway;
      however, recent studies have revealed that autophagy is able to selectively
      engulf specific structures, ranging from proteins to entire organelles. In this
      paper, we discuss recent findings on the mechanisms and physiological
      implications of two selective types of autophagy: ribophagy, the specific
      degradation of ribosomes, and reticulophagy, the selective elimination of
      portions of the ER.

PMID- 22481945
TI  - Plakoglobin: role in tumorigenesis and metastasis.
AB  - Plakoglobin (gamma-catenin) is a member of the Armadillo family of proteins and a
      homolog of beta-catenin. As a component of both the adherens junctions and
      desmosomes, plakoglobin plays a pivotal role in the regulation of cell-cell
      adhesion. Furthermore, similar to beta-catenin, plakoglobin is capable of
      participating in cell signaling. However, unlike beta-catenin that has well
      documented oncogenic potential through its involvement in the Wnt signaling
      pathway, plakoglobin generally acts as a tumor/metastasis suppressor. The exact
      roles that plakoglobin plays during tumorigenesis and metastasis are not clear;
      however, recent evidence suggests that it may regulate gene expression, cell
      proliferation, apoptosis, invasion, and migration. In this paper, we describe
      plakoglobin, its discovery and characterization, its role in regulating cell-cell
      adhesion, and its signaling capabilities in regulation of tumorigenesis and
      metastasis.

PMID- 22481947
TI  - Doppler impedance changes at the fetal brain vessels in a pregnancy affected with
      a multiple combination of uteroplacental anomalies.
AB  - A fetus with a very rare five-fold combination of uteroplacental anomalies,
      bicornuate uterus, short cervix with cervical incompetence, multilobed placenta
      succenturiata, accessory cotyledon within the cervical funneling, and umbilical
      cord insertion into the anomalous cervical cotyledon, presented an early and
      marked decrease at the vertebral and middle cerebral arteries Doppler
      resistances. This cerebral low-impedance state, usually found before labor, and
      considered an adaptive mechanism developed to protect the fetus at term from
      labor asphyxia, was present for an unknown reason at 20 weeks. After the patient
      was treated with vaginal progesterone, the cervix shortening improved and
      markedly, at the same time, the cerebral vascular resistances increased and
      maintained an adequate for gestational age impedance until delivery at 34 weeks.
      As the described uteroplacental anomalies determined a high risk of preterm
      delivery, due to cervical dilation, cord compresion, and placental haemorrhage,
      these fluctuating brain vascular changes might be the result of the fetal
      adaptation to the changes preceding an imminent delivery.

PMID- 22481946
TI  - Cytoskeletal proteins of actinobacteria.
AB  - Although bacteria are considered the simplest life forms, we are now slowly
      unraveling their cellular complexity. Surprisingly, not only do bacterial cells
      have a cytoskeleton but also the building blocks are not very different from the
      cytoskeleton that our own cells use to grow and divide. Nonetheless, despite
      important advances in our understanding of the basic physiology of certain
      bacterial models, little is known about Actinobacteria, an ancient group of
      Eubacteria. Here we review current knowledge on the cytoskeletal elements
      required for bacterial cell growth and cell division, focusing on actinobacterial
      genera such as Mycobacterium, Corynebacterium, and Streptomyces. These include
      some of the deadliest pathogens on earth but also some of the most prolific
      producers of antibiotics and antitumorals.

PMID- 22481948
TI  - A huge adenomatoid odontogenic tumor of maxilla.
AB  - The adenomatoid odontogenic tumor (AOT) is a benign, nonneoplastic
      (hamartomatous) lesion with a slow progressing growth. It occurs in both
      intraosseous and peripheral forms. This paper reports the case of a female aged
      16 years who presented with a swelling in anterior maxilla; canine was missing,
      and a supernumerary tooth was present in the mid line. Radiology revealed a well
      defined radiolucent area associated with impacted canine and root resorption of
      adjacent teeth, which was diagnosed histopathologically as AOT. The patient was
      treated surgically and later rehabilitated with fixed prosthesis.

PMID- 22481949
TI  - Primary Candida guilliermondii Infection of the Knee in a Patient without
      Predisposing Factors.
AB  - Isolated primary candidal infection of joint is extremely rare, with only a few
      reported cases. It occurs as a result of accidental implantations of fungus
      during traumatic procedures, such as surgery, and is usually reported in patients
      with predisposing factors such as immunosuppression, malignancy, and drug abuse.
      If left untreated, irreversible deformity and pain with severe osteoarticular
      destruction occur. Thus, early diagnosis and treatment are important. This paper
      presents a case of 72-year-old man with primary C. guilliermondii infection of
      knee joint without predisposing factors and previous traumatic procedures, who
      was misdiagnosed with advanced degenerative osteoarthritis. Our case is the
      second case of primary C. guilliermondii arthritis of knee to be reported in the
      English-language literature and the first to be successfully treated with total
      knee arthroplasty following IV amphotericin B and oral fluconazole. Primary
      candidal infection of joint is generally asymptomatic or involves only mild pain
      and swelling in the affected knee. Thus, although the majority of knee joint
      infections are of a pyogenic or tuberculous origin, if a patient complains of
      mild pain and swelling in the knee and has mild signs of infection, the
      possibility of fungal infection should be considered.

PMID- 22481950
TI  - Pulmonary hypertension in pulmonary langerhans cell granulomatosis.
AB  - Introduction. Pulmonary Langerhans cell granulomatosis is a rare disease with a
      variable course. In pulmonary Langerhans cell granulomatosis pulmonary
      hypertension is frequent and has an independent prognostic impact. A vasculopathy
      which ist not related to ventilatory disturbance and fibrosis has been
      identified. An arteriopathy and even a venulopathy have been described. Due to
      this possible venulopathy vasodilators carry a significant risk for pulmonary
      congestion and edema. No drugs have been approved until now. Case Presentation.
      One female with PLCG developed severe PH four years after primary diagnosis of
      pulmonary Langerhans cell granulomatosis. Retrospective analysis of lung biopsies
      revealed an arterial vasculopathy at the time of primary diagnosis without
      clinical signs of PH at this time. Sildenafil led to a sustained improvement of
      hemodynamic features and exercise capacity. Conclusion. This paper underlines
      that patients with PLCG with an arterial vasculopathy-related PH might improve
      under sildenafil. Further trials addressing treatment of PH and vasculopathy are
      needed.

PMID- 22481951
TI  - Management of sternal segment dislocation in a child with closed reduction.
AB  - Trauma may lead to sternal fracture or dislocation. Dislocation of a sternal
      segment in the childhood period is very rare as for sternal fractures in
      children. There are only six case reports regarding the issue in the literature.
      Additionally, there is not an established consensus for the treatment of the
      pathology. In this paper we present traumatic dislocation of a sternal body
      segment in a 10-year-old child who was successfully managed conservatively by
      closed reduction together with the review of the literature. Surgical treatment
      is not necessary especially in acute cases. Pathology may be treated with closed
      reduction. Callus formation usually supports the dislocated part of the sternum
      in time.

PMID- 22481952
TI  - Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with
      Disseminated Mycobacterium avium-intracellulare Infection.
AB  - Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular
      organisms, members of the bacterial order actinomycetales. Although Actinomyces
      can behave as copathogen when anatomic barriers are compromised, its coinfection
      with Mycobacterium avium-intracellulare has not previously been reported. We
      present the first reported case of palatal actinomycosis co-infection with
      disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We
      discuss the pathogenesis of the complex condition of this subject.

PMID- 22481953
TI  - Multiple Pyogenic Liver Abscesses Caused by Eggerthella lenta Treated with
      Ertapenem: A Case Report.
AB  - Anaerobic gram-positive bacilli can occasionally be implicated in infections but
      are difficult to identify in culture by conventional biochemical methods. We
      report a case of liver abscesses caused by Eggerthella lenta, identified via 16S
      rRNA sequencing in a previously healthy patient, successfully treated with
      percutaneous drainage and ertapenem.

PMID- 22481954
TI  - Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy after
      ingestion of sildenafil for erectile dysfunction.
AB  - Purpose. To describe a patient who developed bilateral, simultaneous nonarteritic
      anterior ischemic optic neuropathy (NAION) after ingestion of Sildenafil citrate
      (Viagra) for erectile dysfunction. Methods. Observational case report. Results. A
      60-year-old diabetic man noted sudden decrease of vision in both eyes 16 hours
      after his third consecutive 50 mg daily Sildenafil ingestion. A diagnosis of
      bilateral NAION was made and he was treated for three days with
      methylprednisolone 1 g/d intravenously, followed by oral prednisone 75 mg/d.
      Final visual acuity was 20/50 right eye (OD) and 20/20 left eye (OS). He had
      preexisting diabetes. Conclusion. This is the first reported case of simultaneous
      bilateral NAION occurred in a diabetic patient early after Sildenafil intake.
      Patients with predisposing conditions such as diabetes have to be warned against
      the use of PDE inhibitors.

PMID- 22481955
TI  - Isolated cardiac metastasis from colorectal cancer in a 35-year-old man.
AB  - We present the case of a 35-year-old patient who was found to be affected by an
      isolated clinically silent cardiac metastasis despite a negative CT follow-up at
      one year from abdominal surgery for colorectal cancer. CT/PET and tumor marker
      GICA were fundamental in suggesting the diagnosis, which was then confirmed by
      cardiac magnetic resonance and surgical biopsy. This is a very rare modality of
      presentation of cardiac metastasis because of the young age of our patient and
      the absence of disease in other sites.

PMID- 22481956
TI  - Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus
      Associated: Improvement with a Gluten-Free Diet.
AB  - Osteogenesis imperfecta (OI) is a genetic disease, with a connective tissue
      alteration, consisting in the presence of multiple spontaneous fractures or after
      minimal traumatism. Its association with other metabolic processes is rarely
      described. We present the clinical case of a female adult patient of 43 years.
      From her infancy, she has had multiple fractures, needing several surgical
      interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly
      to difficulties in walking remaining in wheel-chair in the last three years, she
      was overweight with morbid obesity (BMI = 45.4) and had a type-II DM associated.
      She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed
      of celiac disease (CD) with increased intraepithelial duodenal infiltration,
      being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten
      free diet (GFD), having lost 6 kg of weight after 6 months, with a good control
      of DM-II and presenting a significant clinical improvement. It is rewarding to
      search the presence of two coincidental metabolic diseases associated to OI,
      specially CD, because of the dramatic clinical benefit in the general found after
      putting on a GFD.

PMID- 22481957
TI  - Varicella Outbreak in an Indian Couple Living in Germany Caused by VZV Clade VI
      Acquired during a Trip to The Netherlands.
AB  - Varicella-zoster virus (VZV), the cause of varicella and zoster, is divided into
      five major clades and four provisional clades, the latter of which have been
      rarely reported worldwide to date. We present a varicella outbreak by the
      provisional clade VI within an Indian couple in Germany returning from a trip to
      Amsterdam. To the best of our knowledge, this is the first case of varicella by
      the VZV clade VI described in Germany, but the disease was acquired in The
      Netherlands.

PMID- 22481958
TI  - Successful treatment with clonazepam and pramipexole of a patient with sleep
      related eating disorder associated with restless legs syndrome: a case report.
AB  - Sleep-related eating disorder (SRED) is characterized by recurrent episodes of
      involuntary eating during sleep period and is often associated with restless legs
      syndrome (RLS). Although pharmacotherapy is recommended for SRED patients, no
      drug have shown promising effects so far. The patient, a 48-year-old Japanese
      housewife, first visited our clinic and complained about nighttime eating. She
      had a history of hypertension, diabetes mellitus, sleep apnea syndrome, and
      depression. Insomnia appeared 10 years before the first visit and she often
      received hypnosedatives; at the same time, she developed nocturnal eating
      episodes. She had amnesia for these episodes, and she felt urge to move her legs
      while sleeping. The patient was diagnosed with SRED and RLS. Reduction in the
      doses of triazolam decreased her nighttime eating frequency, and her complete
      amnesia changed to vague recall of eating during night. Clonazepam 1.0 mg at
      bedtime decreased nocturnal eating frequency from 1 to 2 times per month, though
      sleepwalking remained. Administration of pramipexole 0.125 mg relieved all
      symptoms including SRED, RLS, and sleepwalking. This is the first paper to report
      that the combination of clonazepam and pramipexole therapy-reduced SRED episodes
      and RLS symptoms.

PMID- 22481959
TI  - Stem cells and gene therapy for cartilage repair.
AB  - Cartilage defects represent a common problem in orthopaedic practice.
      Predisposing factors include traumas, inflammatory conditions, and biomechanics
      alterations. Conservative management of cartilage defects often fails, and
      patients with this lesions may need surgical intervention. Several treatment
      strategies have been proposed, although only surgery has been proved to be
      predictably effective. Usually, in focal cartilage defects without a stable
      fibrocartilaginous repair tissue formed, surgeons try to promote a natural
      fibrocartilaginous response by using marrow stimulating techniques, such as
      microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of
      reducing swelling and pain and improving joint function of the patients. These
      procedures have demonstrated to be clinically useful and are usually considered
      as first-line treatment for focal cartilage defects. However, fibrocartilage
      presents inferior mechanical and biochemical properties compared to normal
      hyaline articular cartilage, characterized by poor organization, significant
      amounts of collagen type I, and an increased susceptibility to injury, which
      ultimately leads to premature osteoarthritis (OA). Therefore, the aim of future
      therapeutic strategies for articular cartilage regeneration is to obtain a
      hyaline-like cartilage repair tissue by transplantation of tissues or cells.
      Further studies are required to clarify the role of gene therapy and mesenchimal
      stem cells for management of cartilage lesions.

PMID- 22481960
TI  - Enhancement of methacholine-evoked tracheal contraction induced by bacterial
      lipopolysaccharides depends on epithelium and tumor necrosis factor.
AB  - Inhaled bacterial lipopolysaccharides (LPSs) induce an acute tumour necrosis
      factor-alpha (TNF-alpha-) dependent inflammatory response in the murine airways
      mediated by Toll-like receptor 4 (TLR4) via the myeloid differentiation MyD88
      adaptor protein pathway. However, the contractile response of the bronchial
      smooth muscle and the role of endogenous TNFalpha in this process have been
      elusive. We determined the in vivo respiratory pattern of C57BL/6 mice after
      intranasal LPS administration with or without the presence of increasing doses of
      methacholine (MCh). We found that LPS administration altered the basal and MCh
      evoked respiratory pattern that peaked at 90 min and decreased thereafter in the
      next 48 h, reaching basal levels 7 days later. We investigated in controlled ex
      vivo condition the isometric contraction of isolated tracheal rings in response
      to MCh cholinergic stimulation. We observed that preincubation of the tracheal
      rings with LPS for 90 min enhanced the subsequent MCh-induced contractile
      response (hyperreactivity), which was prevented by prior neutralization of
      TNFalpha with a specific antibody. Furthermore, hyperreactivity induced by LPS
      depended on an intact epithelium, whereas hyperreactivity induced by TNFalpha was
      well maintained in the absence of epithelium. Finally, the enhanced contractile
      response to MCh induced by LPS when compared with control mice was not observed
      in tracheal rings from TLR4- or TNF- or TNF-receptor-deficient mice. We conclude
      that bacterial endotoxin-mediated hyperreactivity of isolated tracheal rings to
      MCh depends upon TLR4 integrity that signals the activation of epithelium, which
      release endogenous TNFalpha.

PMID- 22481961
TI  - Longitudinal analysis of tetanus- and influenza-specific IgG antibodies in
      myeloma patients.
AB  - BACKGROUND: Multiple myeloma (MM) and its therapies may induce a severely
      compromised humoral immunity. We have performed a longitudinal analysis of IgG
      antibody responses against influenza virus (FLU) and tetanus toxoid (TT) as
      surrogate markers for the B cell-mediated immunity in MM patients. METHODS: 1094
      serum samples of 190 MM patients and samples from 100 healthy donors were
      analyzed by ELISA for FLU- and TT-specific antibodies. RESULTS: MM patients
      evidenced lower levels of FLU- and TT-specific antibodies than healthy controls
      (P < 0.001). Immunoreactivity decreased with progressing disease and worsening
      clinical status. Levels of FLU- and TT-specific antibodies increased shortly (0-6
      months) after alloSCT (P < 0.001), a time-period during which intravenous
      immunoglobulin (IVIG) is routinely applied. Thereafter, antibody concentrations
      declined and remained suppressed for 3 years in the case of FLU-specific and for
      more than 5 years in the case of TT-specific antibodies. CONCLUSIONS: We found
      that MM is associated with a profound disease- and therapy-related
      immunosuppression, which is compensated for a few months after alloSCT, most
      likely by application of IVIG. This and the differences regarding the recovery of
      anti-FLU and anti-TT antibody titers during the following years need to be taken
      into account for optimizing IVIG application and immunization after alloSCT.

PMID- 22481962
TI  - The immunology of zoonotic infections.

PMID- 22481963
TI  - Improved activation toward primary colorectal cancer cells by antigen-specific
      targeting autologous cytokine-induced killer cells.
AB  - Adoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells
      showed promise in a number of trials; the activation of CIK cells from cancer
      patients towards their autologous cancer cells still needs to be improved. Here,
      we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer
      patients and engineered those cells with a chimeric antigen receptor (CAR) with
      an antibody-defined specificity for carcinoembryonic antigen (CEA). CIK cells
      thereby gained a new specificity as defined by the CAR and showed increase in
      activation towards CEA+ colon carcinoma cells, but less in presence of CEA-
      cells, indicated by increased secretion of proinflammatory cytokines. Redirected
      CIK activation was superior by CAR-mediated CD28-CD3zeta than CD3zeta signaling
      only. CAR-engineered CIK cells from colon carcinoma patients showed improved
      activation against their autologous, primary carcinoma cells from biopsies
      resulting in more efficient tumour cell lysis. We assume that adoptive therapy
      with CAR-modified CIK cells shows improved selectivity in targeting autologous
      tumour lesions.

PMID- 22481964
TI  - A key role for NF-kappaB transcription factor c-Rel in T-lymphocyte
      differentiation and effector functions.
AB  - The transcription factors of the Rel/NF-kappaB family function as key regulators
      of innate and adoptive immunity. Tightly and temporally controlled activation of
      NF-kappaB-signalling pathways ensures prevention of harmful immune cell
      dysregulation, whereas a loss of control leads to pathological conditions such as
      severe inflammation, autoimmune disease, and inflammation-associated oncogenesis.
      Five family members have been identified in mammals: RelA (p65), c-Rel, RelB, and
      the precursor proteins NF-kappaB1 (p105) and NF-kappaB2 (p100), that are
      processed into p50 and p52, respectively. While RelA-containing dimers are
      present in most cell types, c-Rel complexes are predominately found in cells of
      hematopoietic origin. In T-cell lymphocytes, certain genes essential for immune
      function such as Il2 and Foxp3 are directly regulated by c-Rel. Additionally, c
      Rel-dependent IL-12 and IL-23 transcription by macrophages and dendritic cells is
      crucial for T-cell differentiation and effector functions. Accordingly, c-Rel
      expression in T cells and antigen-presenting cells (APCs) controls a delicate
      balance between tolerance and immunity. This review gives a selective overview on
      recent progress in understanding of diverse roles of c-Rel in regulating adaptive
      immunity.

PMID- 22481965
TI  - B-cell-activating factor affects the occurrence of thyroid autoimmunity in
      chronic hepatitis C patients treated with interferon alpha.
AB  - Chronic hepatitis C (CHC) patients frequently suffer from thyroid disorders
      during interferon therapy. However, the mechanism remains unclear. In this study,
      we investigated the association between serum B-cell-activating factor belonging
      to the TNF family (BAFF) levels and the presence of antithyroid peroxidase
      antibody (anti-TPO) in CHC patients treated with pegylated interferon alpha and
      ribavirin combination therapy. Six months after the therapy, anti-TPO antibody
      was detected in 10 (males, 1; females, 9) of 50 patients. The mean age of these
      patients was higher than that of the anti-TPO-negative patients (61 yr versus 55
      yr). Before treatment, the serum BAFF levels of the anti-TPO-positive patients
      were higher than those of the anti-TPO-negative patients. After starting therapy,
      the serum BAFF levels of both the anti-TPO-positive and -negative patient groups
      were elevated. Our findings suggest that the serum BAFF concentration before
      therapy can predict the risk of thyroid autoimmunity in elderly female patients
      with CHC.

PMID- 22481966
TI  - Cancer/Testis Antigen MAGE-C1/CT7: new target for multiple myeloma therapy.
AB  - Cancer/Testis Antigens (CTAs) are a promising class of tumor antigens that have a
      limited expression in somatic tissues (testis, ovary, fetal, and placental
      cells). Aberrant expression of CTAs in cancer cells may lead to abnormal
      chromosome segregation and aneuploidy. CTAs are regulated by epigenetic
      mechanisms (DNA methylation and acetylation of histones) and are attractive
      targets for immunotherapy in cancer because the gonads are immune privileged
      organs and anti-CTA immune response can be tumor-specific. Multiple myeloma (MM)
      is an incurable hematological malignancy, and several CTAs have been detected in
      many MM cell lines and patients. Among CTAs expressed in MM we must highlight the
      MAGE-C1/CT7 located on the X chromosome and expressed specificity in the
      malignant plasma cells. MAGE-C1/CT7 seems to be related to disease progression
      and functional studies suggests that this CTA might play a role in cell cycle and
      mainly in survival of malignant plasma cells, protecting myeloma cells against
      spontaneous as well as drug-induced apoptosis.

PMID- 22481967
TI  - Perinatal gene-gene and gene-environment interactions on IgE production and
      asthma development.
AB  - Atopic asthma is a complex disease associated with IgE-mediated immune reactions.
      Numerous genome-wide studies identified more than 100 genes in 22 chromosomes
      associated with atopic asthma, and different genetic backgrounds in different
      environments could modulate susceptibility to atopic asthma. Current knowledge
      emphasizes the effect of tobacco smoke on the development of childhood asthma.
      This suggests that asthma, although heritable, is significantly affected by gene
      gene and gene-environment interactions. Evidence has recently shown that
      molecular mechanism of a complex disease may be limited to not only DNA sequence
      differences, but also gene-environmental interactions for epigenetic difference.
      This paper reviews and summarizes how gene-gene and gene-environment interactions
      affect IgE production and the development of atopic asthma in prenatal and
      childhood stages. Based on the mechanisms responsible for perinatal gene
      environment interactions on IgE production and development of asthma, we
      formulate several potential strategies to prevent the development of asthma in
      the perinatal stage.

PMID- 22481968
TI  - Immunotherapy using dendritic cells against multiple myeloma: how to improve?
AB  - Multiple myeloma (MM) is a good target disease in which one can apply cellular
      immunotherapy, which is based on the graft-versus-myeloma effect. This role of
      immune effector cells provides the framework for the development of immune-based
      therapeutic options that use antigen-presenting cells (APCs) with increased
      potency, such as dendritic cells (DCs), in MM. Current isolated idiotype (Id),
      myeloma cell lysates, myeloma dying cells, DC-myeloma hybrids, or DC transfected
      with tumor-derived RNA has been used for immunotherapy with DCs. Immunological
      inhibitory cytokines, such as TGF-beta, IL-10, IL-6 and VEGF, which are produced
      from myeloma cells, can modulate antitumor host immune response, including the
      abrogation of DC function, by constitutive activation of STAT3. Therefore, even
      the immune responses have been observed in clinical trials, the clinical response
      was rarely improved following DC vaccinations in MM patients. We are going to
      discuss how to improve the efficacy of DC vaccination in MM.

PMID- 22481969
TI  - Nonprofessional phagocytosis can facilitate herpesvirus entry into ocular cells.
AB  - Phagocytosis is a major mechanism by which the mediators of innate immunity
      thwart microbial infections. Here we demonstrate that human herpesviruses may
      have evolved a common mechanism to exploit a phagocytosis-like entrapment to gain
      entry into ocular cells. While herpes simplex virus-1 (HSV-1) causes corneal
      keratitis, cytomegalovirus (CMV) is associated with retinitis in
      immunocompromised individuals. A third herpesvirus, human herpesvirus-8 (HHV-8),
      is crucial for the pathogenesis of Kaposi's sarcoma, a common AIDS-related tumor
      of eyelid and conjunctiva. Using laser scanning confocal microscopy, we show that
      successful infection of ocular cell types by all the three viruses, belonging to
      three divergent subfamilies of herpesviruses, is facilitated by induction of F
      actin rich membrane protrusions. Inhibitors of F-actin polymerization and
      membrane protrusion formation, cytochalasin D and latrunculin B, were able to
      block infection by all three viruses. Similar inhibition was seen by blocking
      phosphoinositide 3 kinase signaling, which is required for microbial
      phagocytosis. Transmission electron microscopy data using human corneal
      fibroblasts for HSV-1, human retinal pigment epithelial cells for CMV, and human
      conjunctival epithelial cells for HHV-8 are consistent with the possibility that
      pseudopod-like membrane protrusions facilitate virus uptake by the ocular cells.
      Our findings suggest a novel mechanism by which the nonprofessional mediators of
      phagocytosis can be infected by human herpesviruses.

PMID- 22481970
TI  - Myeloid-derived suppressor cells participate in preventing graft rejection.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells
      and have a tremendous potential to suppress immune responses. MDSCs accumulate
      during tumor progression, autoimmunity, chronic infection, transplantation, and
      other pathological conditions and can potently suppress T-cell function. Here, we
      discuss recent findings that describe the molecular mechanisms of MDSCs
      suppressing T-cell immune responses as well as recent observations that MDSCs may
      have roles in transplant tolerance.

PMID- 22481971
TI  - Multicriteria optimization model for the study of the efficacy of skin antiaging
      therapy.
AB  - The evolution of the cutaneous structure after topical treatment with P63
      antiaging complex, assessed with high frequency ultrasound, is studied by means
      of multicriteria optimization model. Due to the fact that the impact of the
      treatment may influence the quality of life, a medical index which measures, from
      this point of view, the efficacy of the treatment is given, also taking into
      account medical and economical aspects.

PMID- 22481972
TI  - Relationship between concentration difference of different density lipoproteins
      and shear stress in atherosclerosis.
AB  - Previous research has observed concentration polarization in LDL and HDL in the
      arterial system. However, there is no report that links this concentration
      polarization to the development of vascular atherosclerosis (AS). Therefore, the
      purpose of this study is to establish the relationship between concentration
      difference of LDL and HDL and shear stress using a carotid bifurcation vascular
      model. PTFE was employed to create the carotid bifurcation model. Endothelial
      cells were coated on the inner wall of the graft. In a recirculation system, HDL
      and LDL concentration were measured under two different ICA flow velocities at 5
      different locations within our model. We report the following: (1) LDL and HDL
      concentration difference was observed in both high flow and low flow
      environments; (2) the degree of LDL and HDL concentration polarization varied
      depending of high flow and low flow environment; (3) absolute values of
      concentration difference between LDL and HDL at the inner wall surface decreased
      with the increase in shear stress when shear stress was more than 1.5 Pa. This
      variation trend would be more pronounced if shear stress were less than 0.5 Pa.
      Our study suggests that under the action of shear stress, concentration
      differences of LDL or HDL create a disturbance in the balance of atherogenic
      factors and anti-As factors, resulting in the occurrence of AS.

PMID- 22481973
TI  - Constructing an urban population model for medical insurance scheme using
      microsimulation techniques.
AB  - China launched a pilot project of medical insurance reform in 79 cities in 2007
      to cover urban nonworking residents. An urban population model was created in
      this paper for China's medical insurance scheme using microsimulation model
      techniques. The model made it clear for the policy makers the population
      distributions of different groups of people, the potential urban residents
      entering the medical insurance scheme. The income trends of units of individuals
      and families were also obtained. These factors are essential in making the
      challenging policy decisions when considering to balance the long-term financial
      sustainability of the medical insurance scheme.

PMID- 22481974
TI  - Predictive models for maximum recommended therapeutic dose of antiretroviral
      drugs.
AB  - A novel method for predicting maximum recommended therapeutic dose (MRTD) is
      presented using quantitative structure property relationships (QSPRs) and
      artificial neural networks (ANNs). MRTD data of 31 structurally diverse
      Antiretroviral drugs (ARVs) were collected from FDA MRTD Database or package
      inserts. Molecular property descriptors of each compound, that is, molecular
      mass, aqueous solubility, lipophilicity, biotransformation half life, oxidation
      half life, and biodegradation probability were calculated from their SMILES
      codes. A training set (n = 23) was used to construct multiple linear regression
      and back propagation neural network models. The models were validated using an
      external test set (n = 8) which demonstrated that MRTD values may be predicted
      with reasonable accuracy. Model predictability was described by root mean squared
      errors (RMSEs), Kendall's correlation coefficients (tau), P-values, and Bland
      Altman plots for method comparisons. MRTD was predicted by a 6-3-1 neural network
      model (RMSE = 13.67, tau = 0.643, P = 0.035) more accurately than by the multiple
      linear regression (RMSE = 27.27, tau = 0.714, P = 0.019) model. Both models
      illustrated a moderate correlation between aqueous solubility of antiretroviral
      drugs and maximum therapeutic dose. MRTD prediction may assist in the design of
      safer, more effective treatments for HIV infection.

PMID- 22481975
TI  - Modelling of an oesophageal electrode for cardiac function tomography.
AB  - There is a need in critical care units for continuous cardiopulmonary monitoring
      techniques. ECG gated electrical impedance tomography is able to localize the
      impedance variations occurring during the cardiac cycle. This method is a safe,
      inexpensive and potentially fast technique for cardiac output imaging but the
      spatial resolution is presently low, particularly for central locations such as
      the heart. Many parameters including noise deteriorate the reconstruction result.
      One of the main obstacles in cardiac imaging at the heart location is the high
      impedance of lungs and muscles on the dorsal and posterior side of body. In this
      study we are investigating improvements of the measurement and initial
      conductivity estimation of the internal electrode by modelling an internal
      electrode inside the esophagus. We consider 16 electrodes connected around a
      cylindrical mesh. With the random noise level set near 0.05% of the signal we
      evaluated the Graz consensus reconstruction algorithm for electrical impedance
      tomography. The modelling and simulation results showed that the quality of the
      target in reconstructed images was improved by up to 5 times for amplitude
      response, position error, resolution, shape deformation and ringing effects with
      perturbations located in cardiac related positions when using an internal
      electrode.

PMID- 22481976
TI  - On the existence of wavelet symmetries in archaea DNA.
AB  - This paper deals with the complex unit roots representation of archea DNA
      sequences and the analysis of symmetries in the wavelet coefficients of the
      digitalized sequence. It is shown that even for extremophile archaea, the
      distribution of nucleotides has to fulfill some (mathematical) constraints in
      such a way that the wavelet coefficients are symmetrically distributed, with
      respect to the nucleotides distribution.

PMID- 22481977
TI  - The new and computationally efficient MIL-SOM algorithm: potential benefits for
      visualization and analysis of a large-scale high-dimensional clinically acquired
      geographic data.
AB  - The objective of this paper is to introduce an efficient algorithm, namely, the
      mathematically improved learning-self organizing map (MIL-SOM) algorithm, which
      speeds up the self-organizing map (SOM) training process. In the proposed MIL-SOM
      algorithm, the weights of Kohonen's SOM are based on the proportional-integral
      derivative (PID) controller. Thus, in a typical SOM learning setting, this
      improvement translates to faster convergence. The basic idea is primarily
      motivated by the urgent need to develop algorithms with the competence to
      converge faster and more efficiently than conventional techniques. The MIL-SOM
      algorithm is tested on four training geographic datasets representing biomedical
      and disease informatics application domains. Experimental results show that the
      MIL-SOM algorithm provides a competitive, better updating procedure and
      performance, good robustness, and it runs faster than Kohonen's SOM.

PMID- 22481978
TI  - Comparing statistical models to predict dengue fever notifications.
AB  - Dengue fever (DF) is a serious public health problem in many parts of the world,
      and, in the absence of a vaccine, disease surveillance and mosquito vector
      eradication are important in controlling the spread of the disease. DF is
      primarily transmitted by the female Aedes aegypti mosquito. We compared two
      statistical models that can be used in the surveillance and forecast of
      notifiable infectious diseases, namely, the Autoregressive Integrated Moving
      Average (ARIMA) model and the Knorr-Held two-component (K-H) model. The Mean
      Absolute Percentage Error (MAPE) was used to compare models. We developed the
      models using used data on DF notifications in Singapore from January 2001 till
      December 2006 and then validated the models with data from January 2007 till June
      2008. The K-H model resulted in a slightly lower MAPE value of 17.21 as compared
      to the ARIMA model. We conclude that the models' performances are similar, but we
      found that the K-H model was relatively more difficult to fit in terms of the
      specification of the prior parameters and the relatively longer time taken to run
      the models.

PMID- 22481979
TI  - HER2 as a Prognostic Marker in Gastric Cancer - A Systematic Analysis of Data
      from the Literature.
AB  - Through the recent conduct of the ToGA trial, HER2 has shown to be predictive for
      the treatment with trastuzumab in advanced gastric and gastro-oesophageal cancer.
      When it comes to the prognostic properties the situation is different. Despite
      the fact that it is more than 20 years ago since the first studies demonstrating
      an association between a positive HER2 status and poor prognosis were published
      the issue is still controversial. In this current systematic review a large
      number of studies on HER2 and gastric cancer have been reviewed. The studies
      included in this review should fulfill the following two criteria. First
      criterion: The number of patients in each study should be >= 100, and the HER2
      status should have been determined either by immunohistochemistry (IHC) or in
      situ hybridization (ISH). Second criterion: The selected articles should include
      an analysis of the association between the HER2 status and survival or relevant
      clinicopathological characteristics. Forty-two publications with a total of
      12,749 patients fulfilled the two criteria and were reviewed in detail. The
      majority of the publications (71%) showed that a HER2-postive status measured
      either by IHC or ISH was associated with poor survival and/or clinicopathological
      characteristics, such as serosal invasion, lymph node metastases, disease stage,
      or distant metastases. Based on the current analysis a clear trend towards a
      potential role for HER2 as a negative prognostics factor in gastric cancer was
      shown, suggesting that HER2 overexpression and/or amplification is a molecular
      abnormality that might be linked to the development of gastric cancer.

PMID- 22481980
TI  - A Phase II Study of Concurrent Docetaxel, Epirubicin and Cyclophosphamide as a
      Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy with concurrent docetaxel, doxorubicin and
      cyclophosphamide is commonly used for patients with locally advanced breast
      cancer. Epirubicin is another anthracycline used in breast cancer but the
      concurrent use of epirubicin and taxane is not well-established. We conducted a
      single institution, phase II study to assess the efficacy and safety of
      concurrent docetaxel, epirubicin and cyclophosphamide (TEC) as a neoadjuvant
      chemotherapy regimen in breast cancer. METHODS: Patients with newly diagnosed
      locally advanced breast cancer defined as T2 >3 cm, T3, T4 with any N, or any T
      with N1-3 were eligible. A chemotherapy regimen of docetaxel 75mg/m(2),
      epirubicin 75mg/m(2) and cyclophosphamide 600mg/m(2 )was given with filgrastim
      support every 3 weeks for 6 cycles. The primary end-point was pathologic complete
      response rate. RESULTS: Twenty patients were enrolled from 2003 to 2006. The
      median age was 51 (29-70) year-old. Eight patients were premenopausal. Ten
      patients had positive hormone receptors. Four patients had HER2 positive
      receptor. Nineteen patients completed six cycles of TEC chemotherapy. The
      pathologic complete response rate was 25%. Eight of sixteen patients with N1-3
      disease had pathological negative lymph nodes. With a median follow up of 57.5
      (16-71) months, four patients relapsed including one death from recurrence. The
      estimated 5 year relapse-free survival was 79.3% and the 5-year overall survival
      was 94.7%. No patient had cardiac failure or death during treatment. The most
      common grade 3-4 toxicity was neutropenia (35%). CONCLUSION: TEC regimen is a
      well- tolerated and effective neoadjuvant chemotherapy regimen for locally
      advanced breast cancer that results in a pathologic complete response rate of
      25%.

PMID- 22481981
TI  - Targeting the mTOR pathway in Chromophobe Kidney Cancer.
AB  - Chromophobe kidney cancer accounts for approximately 5% of cases of renal cell
      carcinoma (RCC). While the genetics of clear cell RCC has been a major focus of
      research, little is known about the biology of chromophobe tumors. There is ample
      preclinical rationale for the use of targeted therapy in clear cell tumors, and
      agents targeting the VHL/HIF pathway are now widely used in clinical practice.
      However, there is limited experience with targeted agents in non-clear cell
      tumors. Recently, a few case reports have emerged which report the use of mTOR
      inhibitors in chromophobe tumors. Here, we report our experience with targeted
      therapy in a patient with advanced chromophobe RCC who had a durable partial
      response to temsirolimus. We also include a literature review summarizing the
      published experience with targeted therapeutic approaches in chromophobe RCC.
      Additionally, the preclinical rationale for the use of mTOR inhibitors in this
      population based on our characterization of the hereditary form of chromophobe
      kidney cancer, Birt-Hogg-Dube syndrome, is discussed.

PMID- 22481982
TI  - Gossypol Inhibits Electron Transport and Stimulates ROS Generation in Yarrowia
      lipolytica Mitochondria.
AB  - This work studied the effect of gossypol on the mitochondrial respiratory chain
      of Yarrowia lipolytica. The compound was shown to inhibit mitochondrial electron
      transfer and stimulate generation of reactive oxygen species. The inhibition
      kinetics in oxidation of various substrates (NADH, succinate, alpha
      glycerophosphate and pyruvate + malate) by isolated mitochondria was
      investigated. Analysis of the kinetic parameters showed gossypol to inhibit two
      fragments of the mitochondrial electron transfer chain: a) between coenzyme Q and
      cytochrome b with K(IIIi) of 118.3 MUM (inhibition by the noncompetitive type),
      and b) at the level of exogenous NADH dehydrogenase with of K(Ii) 17.2 MUM
      (inhibition by the mixed type).

PMID- 22481983
TI  - Effects of alpha-Particle Radiation on MicroRNA Responses in Human Cell-Lines.
AB  - A variety of alpha (alpha)-particle emitters are found ubiquitously in the
      environment, in commercial/therapeutic prod-ucts and are a potential threat in
      the form of a radiological dispersal device. Our understanding of the biological
      mechanisms and long-term health effects resulting from alpha-particle exposure is
      limited. Exposure to radiation induces modulations of gene networks, possibly
      through microRNAs (miRNAs), which could be targets for studying biological
      effects. In this study, changes in miRNA expression patterns after 0.5 Gy, 1.0 Gy
      and 1.5 Gy of alpha-particle radiation at a low dose-rate of exposure in three
      human cell-lines (A549, THP-1 and HFL) were investigated. The screening of 1,145
      miRNAs across three human cell-lines resulted in unique, cell-specific responses
      with no overlap in miRNA expression observed in the three cell-lines. Prediction
      analysis suggests these alpha-particle induced miRNA mapped to target genes
      related to ribosomal assembly, lung carcinoma development, cell communication and
      keratin sulfate biosynthesis. Taken together, these results suggest that exposure
      to alpha-particle radiation results in cell-type specific responses in gene
      network regulatory processes.

PMID- 22481984
TI  - Is there a role for hypolipidaemic drug therapy in the prevention or treatment of
      microvascular complications of diabetes?

PMID- 22481985
TI  - Agreement of Turkish physiatrists with the assessment in spondyloarthritis
      international society and the European league against rheumatism recommendations
      for the management of ankylosing spondylitis and rheumatoid arthritis.
AB  - BACKGROUND: New developments in the field of targeted therapies or biologic
      agents led more effective management of ankylosing spondylitis (AS) and
      rheumatoid arthritis (RA). Recommendations for the management of rheumatic
      diseases propose to reduce inappropriate use of medications, minimize variations
      among countries, and enable cost-effective use of health care resources.
      OBJECTIVE: The aim this study was to evaluate conceptual agreement of ASsessment
      in SpondyloArthritis International Society (ASAS) and the EUropean League Against
      Rheumatism (EULAR) recommendations for the management of AS and EULAR
      recommendations for RA and to assess the rate of application among Turkish
      physiatrists in daily clinical practice. METHODS: An online survey link has been
      sent to 1756 Turkish physiatrists with e-mails asking to rate agreement on 11
      item ASAS/EULAR AS recommendations and 15-item EULAR RA recommendations with
      synthetic and biological disease-modifying anti-rheumatic drugs. Also barriers
      and difficulties for using biologic agents were assessed. RESULTS: Three hundred
      nine physiatrists (17.5%) completed the survey. The conceptual agreement with
      both recommendations was very high (Level of agreement; mean 8.35+/-0.82 and
      8.90+/- 0.67 for RA and AS recommendations, respectively), and the self-declared
      application of overall recommendations in the clinical practice was also high for
      both RA and AS (72.42% and 75.71%, respectively). CONCLUSION: Turkish
      physiatrists are in good conceptual agreement with the evidence-based
      recommendations for the management of AS and RA. These efforts may serve to
      disseminate the knowledge and increase the current awareness among physicians who
      serve to these patients and also implementation of these recommendations is
      expected to increase as well.

PMID- 22481986
TI  - Computer-aided Image Processing of Angiogenic Histological.
AB  - This article reviews the questions regarding the image evaluation of angiogeneic
      histological samples, particularly the ovarian epithelial cancer. Review is
      focused on the principles of image analysis in the field of histology and
      pathology. The definition, classification, pathogenesis and angiogenesis
      regulation in the ovaries are also briefly discussed. It is hoped that the
      complex image analysis together with the patient's clinical parameters will allow
      an acquiring of a clear pathogenic picture of the disease, extension of the
      differential diagnosis and become a useful tool for the evaluation of drug
      effects. The challenge of the assessment of angiogenesis activity is the
      heterogeneity of several objects: parameters derived from patient's anamnesis as
      well as of pathology samples. The other unresolved problems are the subjectivity
      of the region of interest selection and performance of the whole slide scanning.
      KEYWORDS: Angiogenesis; Image processing; Microvessel density; Cancer; Pathology.

PMID- 22481987
TI  - In-hospital Mortality Characteristics of Women With Acute Myocardial Infarction.
AB  - BACKGROUND: Cardiovascular disease continues to be the leading cause of death in
      women and men in the United States. This study aimed to investigate differences
      in characteristics between those women who died and survived an acute myocardial
      infarction (MI). METHODS: This secondary analysis included 109 women. Demographic
      variables were extracted along with presenting MI symptoms, cardiovascular risk
      factors (family history of cardiovascular disease, patient history of
      cardiovascular disease, diabetes, hypercholesterolemia, hypertension, and smoking
      history), type of MI, time of symptom onset and time of presentation to emergency
      department (ED) for treatment. Descriptive statistics described the sample, t
      tests and chi-square analyzed differences between the groups. RESULTS: There was
      a 12% mortality rate for women experiencing an acute MI. The women who died had a
      mean age of 79 years, approximately 7 years older than those who survived (P =
      0.037). The leading MI presenting symptoms were chest pain and shortness of
      breath. The mean number of cardiovascular risk factors for those who died were
      2.15 compared to 2.75 for those who survived (P = 0.063). The majority of those
      women who survived had a non ST Elevation MI (94%) compared to 54% with a non ST
      Elevation MI who died. Median time to ED presentation was 242.5 minutes for those
      who survived compared to 244 minutes who died (P = 0.951). CONCLUSIONS: These
      data demonstrate a MI mortality profile of women which included an older age, no
      family history of heart disease reported, and a high rate of hypertension. Those
      who died reported chest pain and shortness of breath, with several presenting
      with a syncopal event. In addition, the women represented in this sample had a
      prolonged presentation time for treatment. KEYWORDS: Myocardial infarction;
      Gender; Women; Mortality; Cardiovascular risk factors.

PMID- 22481988
TI  - Blood transfusion practices in total joint arthroplasties in Jamaica.
AB  - BACKGROUND: Major blood loss usually occurs in both hip and knee arthroplasty,
      frequently leading to the need for blood transfusion. This study was performed to
      determine blood transfusion rates and analyze the factors which affected the need
      for blood transfusion in patients who underwent primary unilateral total knee and
      hip arthroplasties at the University Hospital of the West Indies, Jamaica.
      METHODS: A prospective study of 118 patients who underwent unilateral total knee
      and total hip arthroplasties between January 2004 and July 2009 was undertaken.
      Data collected was analyzed using Microsoft Excel 2008, SPSS version 12 and Stata
      version 7.0. RESULTS: Of the 118 patients, 90 (70%) were females. Mean +/-
      standard deviation (SD) age was 65.2 +/- 11.5 years (range 32 - 85 years).
      Osteoarthritis accounted for the majority (88%) of arthroplasties. Mean +/- SD
      estimated blood loss for all arthroplasties was 1195.0 +/- 855.6 ml (range 100 -
      6000 ml). Mean +/- SD duration of surgery for all joint arthroplasties was 226.1
      +/- 63.5 minutes (range 110 - 392 minutes). Mean +/- SD preoperative hemoglobin
      was 12.09 g/dl (range 7.3 - 15.6 g/dl). Average body mass index was 28.9 kg/m(2)
      (range 17.9 - 68.3 kg/m(2)). Seventy-five (64%) patients were transfused and of
      these, 44 patients received allogenic blood only; 20 patients received autologous
      blood only, and eleven patients received both allogenic and autologous blood. 
      The overall blood transfusion rate was 63%. CONCLUSION: In our study, the
      multivariate analysis showed a significant relationship (p = 0.000) only between
      postoperative transfusion and the estimated blood loss. KEYWORDS: Blood
      transfusion practices; Total joint arthroplasties.

PMID- 22481990
TI  - The effects of injection site on the reflux following intravitreal injections.
AB  - BACKGROUND: This study aimed to investigate the effects of injection site on the
      reflux after intravitreal injection. METHODS: One hundred and eighty eyes
      undergoing intravitreal injection including 0.1 ml of triamcinolone acetonide or
      bevacizumab or pegaptanib were divided to six groups (30 patients in each group)
      to compare the vitreal reflux after injection using superotemporal versus
      inferotemporal quadrant. The amount of intraoperative reflux was estimated by
      measuring the width of the subconjunctival bleb. An interventional, prospective,
      comparative clinical trial was applied. RESULTS: The mean bleb width as the
      reflux amount after injection of three drugs was statistically less after the
      inferotemporal injection (1.50 +/- 0.94 mm for triamcinolone acetonide, p <
      0.001; 1.60 +/- 1.07 mm for bevacizumab, p < 0.001; and 1.77 +/- 0.94 mm for
      pegaptanib, p = 0.001) than those in eyes undergoing the superotemporal injection
      (3.20 +/- 1.63 mm for triamcinolone acetonide; 3.07 +/- 1.53 mm for bevacizumab;
      and 2.80 +/- 1.32 mm for pegaptanib). CONCLUSIONS: The injection through
      inferotemporal quadrant provides statistically significant less vitreal reflux
      for intravitreal drug injection. KEYWORDS: Intravitreal injection; Injection
      site; Reflux.

PMID- 22481989
TI  - Accidental chlorine gas intoxication: evaluation of 39 patients.
AB  - BACKGROUND: Chlorine is a known pulmonary irritant gas that may cause acute
      damage in the respiratory system. In this paper, the socio-demographic and
      clinical characteristics of 39 accidentally exposed patients to chlorine gas are
      reported and different emergency treatment modalities are also discussed.
      METHODS: Two emergency departments applications were retrospectively analyzed for
      evaluation of accidental chlorine gas exposure for year 2007. Patients were
      classified into 3 groups according to severity of clinical and laboratory
      findings based on the literature and duration of land of stay in the emergency
      department. The first group was slightly exposed (discharged within 6 hours),
      second group moderately exposed (treated and observed for 24 hours), and third
      group was severely exposed (hospitalized). Most of the patients were initially
      treated with a combination of humidified oxygen, corticosteroids, and
      bronchodilators. RESULTS: The average age was 17.03 +/- 16.01 years (95% CI).
      Seven (17.9%) of them were female and 29 (74.4%) were children. Twenty-four
      patients (61.5%) were included in the first, nine (23.1%) were in second and six
      (15.4%) were in the third group. The presenting symptoms were cough, nausea, and
      vomiting and conjunctiva hyperemia for the first group, first groups symptoms
      plus dyspnea for the second group. Second groups symptoms plus palpitation,
      weakness and chest tightness were for the third group. Cough and dyspnea were
      seen in 64.1% and 30.8% of the patients respectively. No patients died.
      CONCLUSIONS: The authors recommend that non symptomatic or slightly exposed
      patients do not need any specific treatment or symptomatic treatment is
      sufficient. KEYWORDS: Accidental; Chlorine exposure; Chlorine gas; Chlorine
      intoxication; Emergency department.

PMID- 22481991
TI  - Study of matrix metalloproteinase-2 in inguinal hernia.
AB  - BACKGROUND: Abnormal collagen metabolism is thought to play an important role in
      the development of primary inguinal and ventral hernia. The detection of an
      impaired collagen balance both in the tissue as well as in cultured fibroblasts
      underlines the suspicion that the development of hernia is likely to be
      implemented primarily by a disturbance of the fibroblast function and their
      collagen genes. Based on these results we assume that the altered collagen
      synthesis in hernia patients can be regarded as a genetically linked deregulation
      serving as a basic initiating or promoting factor for the development of primary
      inguinal hernias. With the hypothesis that hernia is a local manifestation of a
      systemic disease manifested by increased expression of matrix metallo-proteinase
      2 (MMP-2), a study was planned with following aims: 1) to establish a causal
      association between inguinal hernia and MMP-2; 2) to test the hypothesis that
      hernia is a local manifestation of a systemic disorder rather than a mere local
      mechanical defect. METHODS: A case control study was conducted on 30 subjects of
      each direct and indirect inguinal hernia and 30 controls. DAC-ELISA test was used
      for analysis of serum (preoperative) and tissue samples (fascia transversalis) in
      patients as well as controls. RESULTS: Statistically, serum levels of MMP-2 were
      significantly increased in all the hernia patients as compared to controls. This
      increment was maximum in patients of direct hernia. MMP-2 was not detectable in
      tissue samples. CONCLUSIONS: Hernia is a local manifestation of a systemic
      disease rather than a mere local mechanical defect. KEYWORDS: MMP-2; Matrix
      Metalloproteinase-2; Inguinal hernia; DAC-ELISA; Collagen metabolism; PBST
      Phosphate Buffer Saline Tween-20.

PMID- 22481992
TI  - Effect of escitalopram on white blood cells in patients with major depression.
AB  - BACKGROUND: Immunological dysfunctions in the course of depression are recently
      intensively investigated. Pharmacotherapy of depression is speculated to affect
      immune response. In this study, our objective was to investigate whether
      escitalopram treatment would affect white blood cells in patients with major
      depression. METHODS: Fifteen patients (11 women and 4 men), meeting the criteria
      for a current episode of major depressive disorder, were participated. White
      blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH), monocyte (MONO),
      eosinophyl (EO), and basophyl (BASO) levels were measured at the entry to the
      study. After 8 weeks of open-label treatment with the selective serotonin
      reuptake inhibitor escitalopram (10-20 mg/d), the patients were readmitted and
      the measurements were repeated. RESULTS: At the end of the study, LYMPH was found
      to be significantly decreased compared to the baseline value after 8 weeks
      treatment with escitalopram (p < 0.001). There was not a significant change in
      WBC, NEUT, MONO, EO, and BASO parameters. CONCLUSIONS: The present study has
      shown that escitalopram increased LYMPH in patients with major depression
      according to these results, the possible treatment of depression with
      escitalopram must be carried out with caution, in patients with immunological
      disturbances. KEYWORDS: Escitalopram; Major depression; White blood cells.

PMID- 22481993
TI  - A case of variegate porphyria in association with coeliac disease and
      bisphosphonate associated dental osteonecrosis.
AB  - This case describes an older patient with a rare diagnosis of variegate porphyria
      presenting with acute abdominal pains and bloating, intermittent loose stools and
      jaw pains following surgical repair of an osteoporotic hip fracture. She was
      noted to have acute hyponatraemia. All the abdominal symptoms and the
      hyponatraemia were initially attributed to an acute episode of variegate
      porphyria with an accompanying syndrome of inappropriate antidiuretic hormone
      secretion. However, following further evaluations necessitated by the incomplete
      resolution of the abdominal symptoms, it became apparent that some of the
      persisting symptoms were due to a concurrent and new presentation of serology
      positive coeliac disease. The jaw pains were established to be due to dental
      osteonecrosis in association with the use of bisphosphonate therapy for treatment
      of osteoporosis. The various symptoms and signs subsequently settled uneventfully
      following institution of appropriate management options for the various
      coexisting diagnoses. KEYWORDS: Abdominal pain; Abdominal bloating; Loose stools;
      Hyponatraemia; Variegate porphyria; Coeliac disease; Osteoporosis;
      Bisphosphonates; Osteonecrosis.

PMID- 22481994
TI  - Left atrial myxoma with pleural effusion.
AB  - Cardiac myxomas are histologically benign tumors but they may be lethal because
      of their strategic position. They have variable presentations and excellent
      prognosis after surgical excision. Left atrial myxomas may mimic mitral stenosis
      and is very rarely associated with pleural effusion. We presented a case of left
      atrial myxoma blocking mitral orifice and causing recurrent pulmonary edema and
      pleural effusions in this report. KEYWORDS: Left Atrial; Myxoma; Pleural
      effusion.

PMID- 22481995
TI  - Tumour to tumour metastasis of malignant melanoma to intracranial tumour.
AB  - Tumours can metastasize to sites of other tumours but this is a rare event. The
      phenomenon has been well described in primary tumours of the lung and breast.
      This has been described in melanomas but as very rare occurrence. We describe a
      case of a malignant melanoma that metastasized to a pre-existing meningioma. We
      have tried to highlight this phenomenon in patient with melanoma and need for
      close vigilance of other pre-existing tumours to identify early metastasis.
      KEYWORDS: Melanoma; Metastasis; Tumour to Tumor; Intracranial; Meningioma.

PMID- 22481996
TI  - Meperidine induced seizure in a patient with lyme borreliosis.
AB  - A 15 years old child with Lyme borreliosis was treated with meperidine via a
      patient controlled analgesia (PCA) pump for pain management. He had no history of
      seizure and had normal hepatic and renal functions. At the 7th hour of meperidine
      PCA delivery, generalized tonic-clonic seizure was developed and successfully
      suppressed with antiepileptics and no neurologic sequel was occurred. The total
      meperidine consumption in the patient was quite lower than the recommended doses
      with PCA. Although Lyme disease might also cause seizure activities, the timing
      of the seizures was related with the accumulation of normeperidine which is the
      main metabolite of meperidine with central nervous system stimulant effect. The
      meperidine pain management on patients with Lyme syndrome should be reconsidered
      to avoid undesired effects.Keywords.

PMID- 22481997
TI  - Hemorrhage from a pituitary macroadenoma after a minor trauma.

PMID- 22481998
TI  - Floating-electrode enhanced constriction dielectrophoresis for biomolecular
      trapping in physiological media of high conductivity.
AB  - We present an electrokinetic framework for designing insulator constriction-based
      dielectrophoresis devices with enhanced ability to trap nanoscale biomolecules in
      physiological media of high conductivity, through coupling short-range
      dielectrophoresis forces with long-range electrothermal flow. While a 500-fold
      constriction enables field focusing sufficient to trap nanoscale biomolecules by
      dielectrophoresis, the extent of this high-field region is enhanced through
      coupling the constriction to an electrically floating sensor electrode at the
      constriction floor. However, the enhanced localized fields due to the
      constriction and enhanced current within saline media of high conductivity (1
      S/m) cause a rise in temperature due to Joule heating, resulting in a hotspot
      region midway within the channel depth at the constriction center, with
      temperatures of ~8 degrees -10 degrees K above the ambient. While the resulting
      vortices from electrothermal flow are directed away from the hotspot region to
      oppose dielectrophoretic trapping, they also cause a downward and inward flow
      towards the electrode edges at the constriction floor. This assists biomolecular
      trapping at the sensor electrode through enabling long-range fluid sampling as
      well as through localized stirring by fluid circulation in its vicinity.

PMID- 22481999
TI  - Optoelectronic Properties of Carbon Nanorings: Excitonic Effects from Time
      Dependent Density Functional Theory.
AB  - The electronic structure and size-scaling of optoelectronic properties in
      cycloparaphenylene carbon nanorings are investigated using time-dependent density
      functional theory (TDDFT). The TDDFT calculations on these molecular
      nanostructures indicate that the lowest excitation energy surprisingly becomes
      larger as the carbon nanoring size is increased, in contradiction with typical
      quantum confinement effects. In order to understand their unusual electronic
      properties, I performed an extensive investigation of excitonic effects by
      analyzing electron-hole transition density matrices and exciton binding energies
      as a function of size in these nanoring systems. The transition density matrices
      allow a global view of electronic coherence during an electronic excitation, and
      the exciton binding energies give a quantitative measure of electron-hole
      interaction energies in the nanorings. Based on overall trends in exciton binding
      energies and their spatial delocalization, I find that excitonic effects play a
      vital role in understanding the unique photoinduced dynamics in these carbon
      nanoring systems.

PMID- 22482000
TI  - The magical number four: A biological, historical and mythological enigma.
AB  - Precise recognition of small object numbers without counting is a widespread
      phenomenon. It is well documented for humans and for a series of non-human
      vertebrates. Recently this has been confirmed for an invertebrate, the
      honeybee.(1) This type of inborn numerical competence has been named
      "subitizing", from the Latin subito = suddenly, immediately. It differs from the
      classical, sequential counting which has to be trained, starting with the help of
      our fingers. For humans it had been established since 1871 by Jevons(2) that only
      up to four objects are precisely recognized and memorized. Under conditions which
      do not allow sequential counting, mistakes start to occur in case of more than
      four objects. This result has been confirmed whenever the range of visual
      attention has been carefully tested under a variety of rigorous conditions. It
      provides the basis for a novel hypothesis about the evolution of counting and
      numbering systems in ancient civilizations.(3)  

PMID- 22482001
TI  - Social biases determine spatiotemporal sparseness of ciliate mating heuristics.
AB  - Ciliates become highly social, even displaying animal-like qualities, in the
      joint presence of aroused conspecifics and nonself mating pheromones. Pheromone
      detection putatively helps trigger instinctual and learned courtship and
      dominance displays from which social judgments are made about the availability,
      compatibility, and fitness representativeness or likelihood of prospective mates
      and rivals. In earlier studies, I demonstrated the heterotrich Spirostomum
      ambiguum improves mating competence by effecting preconjugal strategies and
      inferences in mock social trials via behavioral heuristics built from Hebbian
      like associative learning. Heuristics embody serial patterns of socially relevant
      action that evolve into ordered, topologically invariant computational networks
      supporting intra- and intermate selection. S. ambiguum employs heuristics to
      acquire, store, plan, compare, modify, select, and execute sets of mating
      propaganda. One major adaptive constraint over formation and use of heuristics
      involves a ciliate's initial subjective bias, responsiveness, or preparedness, as
      defined by Stevens' Law of subjective stimulus intensity, for perceiving the
      meaningfulness of mechanical pressures accompanying cell-cell contacts and
      additional perimating events. This bias controls durations and valences of
      nonassociative learning, search rates for appropriate mating strategies,
      potential net reproductive payoffs, levels of social honesty and deception,
      successful error diagnosis and correction of mating signals, use of insight or
      analysis to solve mating dilemmas, bioenergetics expenditures, and governance of
      mating decisions by classical or quantum statistical mechanics. I now report this
      same social bias also differentially affects the spatiotemporal sparseness, as
      measured with metric entropy, of ciliate heuristics. Sparseness plays an
      important role in neural systems through optimizing the specificity, efficiency,
      and capacity of memory representations. The present findings indicate sparseness
      performs a similar function in single aneural cells by tuning the size and
      density of encoded computational architectures useful for decision making in
      social contexts.

PMID- 22482002
TI  - Co-regulation of the arf-activation cycle and phospholipid-signaling during golgi
      maturation.
AB  - The Golgi apparatus is the central protein sorting station inside eukaryotic
      cells. Although many regulators of Golgi trafficking have been identified, little
      is known about their crosstalk. Both the Arf activation cycle and
      phosphatidylinositol 4-phosphate metabolism have been recognized as key processes
      in the regulation of vesicular transport from this organelle. However, the
      mechanism ensuring the proper co-regulation of these processes has eluded our
      understanding thus far. We recently identified a physical interaction between the
      late yeast Golgi Arf activator Sec7p and the PI4-kinase Pik1p, and showed that
      the two proteins cooperate in the formation of clathrin-coated vesicles. This
      finding gives the first insight on the coordinated generation of a dual key
      signal by a small GTPase and a signaling phospholipid at the Golgi. In addition,
      it opens new perspectives for a better understanding of Golgi maturation through
      coordinated regulation of highly dynamic lipid and protein composition of this
      organelle.

PMID- 22482003
TI  - Visualizing the high curvature regions of post-mitotic nascent nuclear envelope
      membrane.
AB  - We previously reported that mitotic endoplasmic reticulum (ER) membrane cisternae
      or sheets directly assemble mammalian nuclear envelope (NE) at the end of
      mitosis. In this study, we investigated the dynamics of the high curvature
      regions of partially assembled nuclear envelope membrane using reticulon4a as a
      probe. We found that, after sorting out reticulon4a from the nascent NE membrane
      sheets, reticulon4a is specifically localized to the leading edges. Our 3D time
      lapse images suggested that ER tubules could be incompetent in assembling the NE
      membrane. Our findings suggest a possible role of reticulons at the leading edges
      during the NE re-assembly and provide further evidences that the mitotic assembly
      of NE is by ER cisternae rather than tubules.

PMID- 22482004
TI  - In silico characterization of a nitrate reductase gene family and analysis of the
      predicted proteins from the moss Physcomitrella patens.
AB  - Assimilatory nitrate reductase (NR; EC 1.7.1.1-3) catalyzes the reduction of
      nitrate to nitrite. This enzyme has a conserved structure common to fungi, algae
      and plants. However, some differences in the amino acid sequence between plant
      and algal NR suggest that the activity regulation mechanisms have changed during
      plant evolution. Since only NRs from angiosperms have been studied, the search
      and analysis of NR genes and proteins from the moss Physcomitrella patens, a
      basal land plant, was performed to widen the knowledge of land plant NR
      structure. A family of three nr genes, named ppnia1;1, ppnia1;2 and ppnia2, was
      localized in the P. patens genome. The predicted proteins are canonical NRs with
      the conserved domains Molybdene-Cytochorme b -Cytochrome b reductase and possess
      20 amino acid residues important for the enzymatic function conserved in plant
      and algal NRs. Interestingly, moss NRs lack a consensus sequence, common to
      angiosperm NRs, that is a target for posttranslational regulation. A phylogenetic
      tree with embryophyte and green algae NR sequences was constructed and P. patens
      NRs localized at the base of embryophyte NR evolution. The data presented here
      suggest that bryophytes and vascular plants have different systems to regulate NR
      activity.

PMID- 22482005
TI  - Is cohesin required for spindle-pole-body/centrosome cohesion?
AB  - Centrosomes are microtubule-organizing centers that nucleate spindle microtubules
      during cell division. In budding yeast, the centrosome, often referred to as the
      spindle pole body, shares structural components with the centriole, the central
      core of the animal centrosome. The parental centrosome is duplicated when DNA
      replication takes place. Like sister chromatids tethered together by cohesin,
      duplicated centrosomes are linked and then separate to form the bipolar spindle
      necessary for chromosome segregation. Recent studies have shown that cohesin is
      also localized to the animal centrosome and is perhaps directly involved in
      engaging paired centrioles. Here we discuss the potential role of cohesin in
      mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose
      that the coordination of chromosome segregation with centrosome cohesion and
      duplication is mediated by the antagonistic interaction between the Aurora kinase
      and the Polo kinase and that the role of cohesin in centrosome regulation appears
      to be indirect in budding yeast.

PMID- 22482006
TI  - High pressure, a tool to switch between soluble and fibrillar prion protein
      structures.
AB  - The native soluble as well as different aggregated states of recombinant prion
      proteins are highly sensitive to high pressure. On the one hand, its application
      to the native alpha-helical protein induces reversibly a metastable structure
      that relaxes to amyloid fibrils after prolonged incubation. On the other hand,
      its application to synthetic prion amyloid fibrils leads to partial
      disaggregation into native monomers as well as to proto-filaments that have lost
      several amyloid features. In addition, heat-induced beta-sheet prion protein
      aggregates are dissolved and revert into alpha-helical monomers by applying high
      pressure. This profound pressure sensitivity of prion protein structure is
      explained by large volume differences of the different structural states. Hence,
      pressure appears as a suitable thermodynamic parameter for exploring the highly
      complex conformational landscape of prion protein. Its further analysis should
      help identifying prion protein structural states that are on the pathogenic
      pathway.

PMID- 22482007
TI  - The maintenance of mitochondrial genetic stability is crucial during the
      oncogenic process.
AB  - The main energetic resources of the cell are the mitochondria. As such, these
      organelles control a number of processes related to the life and death of the
      cell and also have a prominent function in the maintenance of tumor cells. In the
      last years, several authors have proposed an active role for mitochondria in
      tumorigenesis, more specifically concerning somatic mutations in mitochondrial
      DNA (mtDNA). Here, we wanted to evaluate this hypothesis based on the conclusions
      obtained in a model of gliomagenesis with elevated levels of ROS (reactive oxygen
      species), a toxic by-product of tumor metabolism. According to our findings, none
      of the mtDNA variants were found relevant to the tumoral process or suggest the
      involvement of mitochondria in tumorigenesis beyond the metabolic requirements of
      the tumoral cell. We conclude that there is not enough evidence to support the
      claim that mitochondrial instability holds any relevant role in the tumoral
      process.

PMID- 22482008
TI  - Active actin gels.
AB  - The self-organization of actin filaments is a topic that links cell biology with
      condensed matter physics. In vitro assays allow precise manipulation of component
      mechanical and chemical properties, needed for rigorous tests of theoretical
      models. We review recent work on in vitro motility assays that documented
      emergence of ordered actin filament microdomains powered by myosin motor proteins
      at high filament densities. Motor and filament surface density and
      mechanochemical cycle kinetics are additional parameters under current
      investigation. Individual filament collisions have been studied in order to
      elucidate the emergent population behavior. Apolar, weak  interactions evidenced
      by local filament deformations during crossover events are attenuated at high
      motor densities. Theoretical analysis requires refinement of rigid rod filament
      models. In intact cells, accessory proteins modulate actin filament length,
      bundling or sliding and this gives rise to complex emergent structures and
      behaviors such as cell motility and chemotaxis. The development of generic,
      mechanical and biochemical frameworks with predictive power that link molecular
      properties with micro- and macroscopic phenomena seen in living cells requires
      dialogue between theoreticians and experimentalists.

PMID- 22482009
TI  - Hitching a ride:  Vector feeding and virus transmission.
AB  - The majority of plant viruses rely on insect vectors for transmission. Insects
      with piercing-sucking mouthparts are the most common and efficient vectors
      because, they are able to inject viruses into specific plant tissues. Acquisition
      and inoculation of viruses occurs during specific vector feeding behaviors, and
      feeding behavior varies greatly among insects with piercing-sucking mouthparts.
      In this review we provide an overview of the feeding behavior of the major insect
      vectors with piercing sucking mouthparts: aphids, whiteflies, mealybugs, hoppers,
      and thrips. We briefly review the different mechanisms of plant virus
      transmission by these insects, and discuss how each mechanism requires a vector
      that engages in specific feeding behaviors, and how differences in feeding
      behavior among these insects can determine which viruses they are capable of
      transmitting. We also discuss recent findings indicating that plant viruses can
      directly modify their vector's behavior in a way that enhances transmission to a
      host plant.

PMID- 22482011
TI  - Fitness costs associated with chemical signaling.
AB  - The production, maintenance and transmission of chemical signals often entail
      costs. Costs can arise, for instance, if signal production depends on the
      availability of limited nutritional resources or if signal transmission leads to
      attraction of predators. Many species effectively reduce these costs by signaling
      at specific times or in certain contexts only. We previously reported that
      breeding burying beetle females facultatively adjust their pheromone emission in
      response to their social environment, emitting high amounts of their chemical
      signal in the presence of a male partner, but not when providing uniparental
      care. Here we present data showing that chemical signaling is costly, and that
      higher investments in signaling result in reduced clutch sizes, but not a shorter
      life span, in the burying beetle Nicrophorus vespilloides.

PMID- 22482010
TI  - Vesicle formation within endosomes: An ESCRT marks the spot.
AB  - Vesicle-mediated cargo transport within the endomembrane system requires precise
      coordination between adaptor molecules, which recognize sorting signals on
      substrates, and factors that promote changes in membrane architecture. At
      endosomal compartments, a set of protein complexes collectively known as the
      ESCRT machinery sequesters transmembrane cargoes that harbor a ubiquitin
      modification and packages them into vesicles that bud into the endosome lumen.
      Several models have been postulated to describe this process. However, consensus
      in the field remains elusive. Here, we discuss recent findings regarding the
      structure and function of the ESCRT machinery, highlighting specific roles for
      ESCRT-0 and ESCRT-III in regulating cargo selection and vesicle formation.

PMID- 22482012
TI  - Molecular control of compound Exocytosis:  A key role for VAMP8.
AB  - Exocytosis is the process of fusion of a membrane-bound vesicle with the cell
      membrane and subsequent release of the vesicle content to the outside. It is now
      widely accepted that SNAREs (soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors) proteins are key components in the molecular machinery of
      exocytosis. SNARE proteins on the vesicle membrane selectively form complexes
      with specific SNAREs on the cell membrane. In a variant of exocytosis, called
      compound exocytosis, secretory vesicles still fuse with the cell membrane but
      vesicle-to-vesicle fusion enhances secretory output. Two types of compound
      exocytosis occur, either vesicles fuse with each other and then fuse with the
      cell membrane, or a vesicle fuses with the cell membrane and then becomes a
      target for further vesicles to fuse with it. It is expected that SNAREs are
      important for vesicle-to-vesicle fusion but the mechanism(s) that control these
      processes is unknown. In our recent paper (Behrendorff et al. 2011) we provide
      evidence that VAMP8 (a Q-SNARE) is essential in regulating compound exocytosis.
      Here we discuss the implications of our findings with reference to a new model
      for the control of vesicle-to-vesicle fusion.

PMID- 22482013
TI  - Munc13-4*rab27 complex tethers secretory lysosomes at the plasma membrane.
AB  - Natural Killer (NK) cells and Cytotoxic T lymphocytes (CTL) are critical for the
      immune response against virus infections or transformed cells. They kill target
      cells via polarized exocytosis of lytic proteins from secretory lysosomes (SL).
      Rab27a and munc13-4 interact directly and are required for target cell killing.
      How they cooperate in the intricate degranulation process is not known. We
      identified critical residues in munc13-4 for rab27 interaction and tested binding
      mutants in several complementation assays. In a rat mast cell line we replaced
      endogenous munc13-4 with ectopically expressed munc13-4 constructs. Unlike wild
      type munc13-4, binding mutants fail to rescue beta-hexosaminidase secretion. In
      accord, expression of binding mutants in CTL of Familial Hemophagocytic
      Lymphohistiocytosis type 3 patients, does not rescue CD107 appearance on the
      plasma membrane. Total Internal Reflection Fluorescence (TIRF) imaging shows that
      munc13-4*rab27a restricts motility of SL in the subapical cytoplasm. We propose
      that rab27*munc13-4 tethers SL to the plasma membrane, a requirement for
      formation of a cognate SNARE complex for fusion.

PMID- 22482014
TI  - Endocannabinoid-binding CB1 and TRPV1 receptors as modulators of sperm
      capacitation.
AB  - Mammalian spermatozoa reach the ability to fertilize only after they complete a
      complex series of physical-chemical modification, the capacitation. Recently, the
      endocannabinoid-binding type-1cannabinoid receptor (CB1) and transient receptor
      potential vanilloid 1 (TRPV1) channel have been proposed to play a key role in
      the control of capacitation. In particular CB1, acting via a Gi protein/cAMP/PKA
      pathway, maintains low cAMP levels in early stages of post ejaculatory life of
      male gametes. By this way it promotes the maintenance of membrane stability, thus
      avoiding the premature fusion of plasma membrane (PM) and outer acrosome membrane
      (OAM), which is mandatory for the exocytosis of acrosome content. TRPV1, on the
      contrary, becomes active during the latest stages of capacitation, and allows the
      rapid increase in intracellular calcium concentration that leads to the removal
      of the F-actin network interposed between PM and OAM, leading to their fusion
      and, ultimately, to the acrosome reaction.

PMID- 22482015
TI  - The extracellular matrix remodeled: Interdependency of matrix proteolysis, cell
      adhesion, and force sensing.
AB  - Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP-14) is regarded as the
      prototype of a membrane- tethered protease. It drives fundamental biological
      processes ranging from embryogenesis to cancer metastasis. The proteolytic
      cleavage of proteins by MT1-MMP can rapidly alter the biophysical properties of a
      cell's microenvironment. Cell's must thus be able to sense and react to these
      alterations and transduce these effectively in biochemical signals and cell
      responses. Although many cells react as acutely to such physical stimuli as they
      do to chemical ones, the regulatory effects of these have been less extensively
      explored. In order to investigate a possible interdependency of proteolytic
      matrix cleavage by MT1-MMP and the generation and sensing of force by cells, a
      model system was established which exploits the properties of a matrix array of
      parallel collagen-I fibers. The resulting an-isotropy of the matrix with high
      tensile strength along the fibers and high mobility perpendicular to it allows
      the convenient detection of bundling and cleavage of the collagen fibers, as well
      as spreading and durotaxis of the cells. In summary, we have demonstrated that
      cell adhesion, force generation, and force sensing are vital for the regulation
      of MT1-MMP for efficient cleavage of collagen-I.

PMID- 22482016
TI  - Munc18-1, exocytotic fusion pore regulation and local membrane anisotropy.
AB  - The release of hormones and neurotransmitters from vesicles can be modified by
      the regulation of the fusion pore, an aqueous channel that forms upon the fusion
      of the vesicle membrane with the plasma membrane. However, the mechanisms are
      unclear. Munc18-1 protein interacts with Syntaxin1 (Synt 1), a member of the
      SNARE proteins, which plays an important role in exocytosis. It has been shown
      that Munc18-1 has multiple roles, both in pre- and post-fusion stages of
      exocytosis. It regulates the traffic of Synt1 to the plasma membrane. By
      inhibiting the tethering of the vesicle SNARE protein Synaptobrevin 2 (Syb2)
      solely to Synt1 at the plasma membrane, but favoring the vesicular tethering to
      the preformed binary cis SNARE complex of Synt1A-SNAP25B, Munc18-1 is tuning
      vesicle docking and the membrane merger process. Additionally, Munc18-1 affects
      exocytosis at the post-fusion stage by regulating the fusion pore properties
      (i.e., dwell-time and fusion pore diameter). Among many possible mechanisms that
      may regulate the fusion pore, but have never been considered previously, is the
      influence of Munc18-1 on the membrane anisotropy, which determines the local
      spontaneous membrane curvature and the architecture of the fusion pore. We here
      propose that Munc18-1 affects the fusion pore by modulating the dynamic local
      (re)arrangement of anisotropic membrane components within the highly curved
      fusion pore nanostructure, to which proteins, lipids or their complexes can
      participate.

PMID- 22482017
TI  - Uncovering the complexity of ant foraging trails.
AB  - The common garden ant Lasius niger use both trail pheromones and memory of past
      visits to navigate to and from food sources. In a recent paper we demonstrated a
      synergistic effect between route memory and trail pheromones: the presence of
      trail pheromones results in experienced ants walking straighter and faster. We
      also found that experienced ants leaving a pheromone trail deposit less
      pheromone. Here we focus on another finding of the experiment: the presence of
      cuticular hydrocarbons (CHCs), which are used as home range markers by ants, also
      affects pheromone deposition behavior. When walking on a trail on which CHCs are
      present but trail pheromones are not, experienced foragers deposit less pheromone
      on the outward journey than on the return journey. The regulatory mechanisms ants
      use during foraging and recruitment behavior is subtle and complex, affected by
      multiple interacting factors such as route memory, travel direction and the
      presence trail pheromone and home-range markings.

PMID- 22482018
TI  - Contribution of mitochondrial network dynamics to intracellular ROS signaling.
AB  - Oxidative stresses can induce rapid depolarization of inner mitochondrial
      membrane potential and subsequent impairment of oxidative phosphorylation.
      Damaged mitochondria produce more reactive oxygen species (ROS), particularly the
      superoxide anion (O2-) and hydrogen peroxide (H(2)O(2)), which potentiate
      mitochondria-driven ROS propagation, so-called ROS-induced ROS release (RIRR),
      via activation of an inter-mitochondrial signaling network. In this context,
      mitochondrial network dynamics, such as their density, number, and spatial
      distribution, can affect mitochondria-driven ROS propagation. To investigate this
      inter-mitochondrial communication, we developed a mathematical model using an
      agent-based modeling approach, and tested the effect of mitochondrial network
      dynamics on RIRR for mitochondria under various conditions. Simulation results
      show that mitochondrial network dynamics are critical determinants of inter
      mitochondrial ROS signaling patterns and main messenger ROS molecules. We further
      elucidated the potential mechanism of these actions, which is conversion of major
      messenger molecules involved in ROS signaling. Collectively, we propose that
      mitochondrial network dynamics can determine cellular responses to oxidative
      stress by switching the molecular species involved in cellular signaling.

PMID- 22482019
TI  - Linking differences in membrane tension with the requirement for a contractile
      actomyosin scaffold during exocytosis in salivary glands.
AB  - In all the major secretory organs regulated exocytosis is a fundamental process
      that is used for releasing molecules in the extracellular space. Molecules
      destined for secretion are packaged into secretory vesicles that fuse with the
      plasma membrane upon the appropriate stimulus. In exocrine glands, large
      secretory vesicles fuse with specialized domains of the plasma membrane, which
      form ductal structures that are in direct continuity with the external
      environment and exhibit various architectures and diameters. In a recent study,
      we used intravital microscopy to analyze in detail the dynamics of exocytic
      events in the salivary glands of live rodents under conditions that cannot be
      reproduced in in vitro or ex vivo model systems. We found that after the opening
      of the fusion pore large secretory vesicles gradually collapse with their
      limiting membranes being completely absorbed into the apical plasma membrane
      canaliculi within 40-60 sec. Moreover, we observed that this controlled collapse
      requires the contractile activity of actin and its motor myosin II, which are
      recruited onto the large secretory vesicles immediately after their fusion with
      the plasma membrane. Here we suggest that the actomyosin complex may be required
      to facilitate exocytosis in those systems, such as the salivary glands, in which
      the full collapse of the vesicles is not energetically favorable due to a
      difference in membrane tension between the large secretory vesicles and the
      canaliculi.

PMID- 22482020
TI  - Intracellular signaling controlled by the endosomal-exosomal pathway.
AB  - Tight control of intracellular signaling is essential for developmental processes
      such as cell differentiation, migration but also for maintaining tissue
      homeostasis. Disruption in the control of these signaling pathways can result in
      cell death (apoptosis), anergy or uncontrolled cell proliferation and growth
      leading to cancer. In multicellular organisms, timely termination of signaling is
      thus equally important as initiation. Known pathways for downregulating membrane
      receptor-mediated signaling are mediated via specialized endosomal organelles
      known as lysosomes and proteosomes that degrade such proteins in the cytoplasm.
      An alternative pathway for attenuating receptor-mediated signaling was recently
      discovered independently by the group of M. Caplan and our own group.1,2 It
      appears that apart from the classical protein degradation machineries, the
      release of signaling proteins also effectively restricts signaling of at least
      two major signal transduction routes; the canonical Wnt/beta-catenin and NFkappaB
      pathways. Expelling proteins from the cell, rather than coordinated degradation
      in lysosomes may involve defined protein modifications, such as ubiquitination,
      myristyolation, and/or palmitoylation, but little experimental data are currently
      available. Although the secretion of proteins via exosomes starts by accumulation
      within multivesicular bodies (MVBs), a key distinction with degredatory MVBs is
      that exosome-producing MVBs seem to preferentially fuse with the plasmamembrane
      (Fig. 1). Here we discuss the latest developments in the biology of exosomes and
      their unexpected effect on intracellular signal transduction.

PMID- 22482021
TI  - The interaction of Hsc70 protein with fibrillar alpha-Synuclein and its
      therapeutic potential in Parkinson's disease.
AB  - We recently described the effect of the constitutively expressed chaperone, Hsc70
      protein, on alpha-Synuclein aggregation, a phenomenon associated with Parkinson
      disease. In vitro, Hsc70 binds to soluble alpha-Syn and slows down its assembly
      into fibrils. Hsc70 also binds fibrillar alpha-Syn, 5-fold tighter than soluble
      alpha-Syn. This interaction reduces the cytotoxicity associated with naked alpha
      Syn fibrils. Herein, we discuss the feasibility of engineering a "minichaperone"
      which could be used against alpha-Syn assembly propagation in Parkinson disease:
      taking what is necessary and sufficient within Hsc70 to protect against the
      damaging repercussions of high molecular weight alpha-Syn species' passage from
      one neuron to another in the brain.

PMID- 22482023
TI  - Rho proteins crosstalk via RhoGDIalpha:  At random or hierarchically ordered?
AB  - The small GTPases of the Rho family are key signaling molecules regulating a
      plethora of biological pathways. They can exert diverse, sometimes opposite,
      contributions to specific cellular processes explaining why their regulation and
      their crosstalk must be finely tuned. Several mechanisms driving crosstalk
      between Rho GTPases have been described in the literature. They implicate
      proteins regulating their activity or common downstream effectors. Among the
      proteins regulating Rho GTPases cycling, RhoGDIs were viewed until very recently
      as passive inhibitors. Here, we will focus on recent data supporting a role for
      RhoGDIalpha in the crosstalk between RhoGTPases and present our results
      suggesting that "preferential" RhoGDIalpha-mediated crosstalk takes place between
      closely related Rho GTPases.

PMID- 22482022
TI  - Quorum sensing-controlled buoyancy through gas vesicles: Intracellular bacterial
      microcompartments for environmental adaptation.
AB  - Gas vesicles are gas-filled microcompartments produced by many cyanobacteria and
      haloarchaea to regulate buoyancy and control positioning in the water column.
      Recently we identified the first case of gas vesicle production by a member of
      the Enterobacteriaceae, Serratia sp ATCC39006. Gas vesicle production enabled
      colonisation of the air-liquid interface and was positively regulated in low
      oxygen conditions, suggesting development of these intracellular organelles is an
      adpative mechanism facilitating migration to the water surface. Vesicle
      production was also regulated by the intercellular communication molecule N
      butanoyl-L-homoserine lactone (BHL) showing that gas vesicle production is
      controlled at the population level, through quorum sensing, with BHL acting as a
      morphogen. Gas vesicle production was also reciprocally regulated with flagella
      driven swarming motility by the global regulatory protein RsmA, suggesting a fork
      in the regulatory pathway that controls induction of these distinct modes of
      mobility. Here we discuss these findings in the context of the interesting
      physiology of Serratia 39006 and highlight future prospects for gas vesicle
      research in this highly tractable strain.

PMID- 22482024
TI  - Genomics of Megavirus and the elusive fourth domain of Life.
AB  - We recently described Megavirus chilensis, a giant virus isolated off the coast
      of Chile, also replicating in fresh water acanthamoeba. Its 1,259,197-bp genome
      encodes 1,120 proteins and is the largest known viral genome. Megavirus and its
      closest relative Mimivirus only share 594 orthologous genes, themselves sharing
      only 50% of identical residues in average. Despite this divergence, comparable to
      the maximal divergence exhibited by bacteria within the same division (e.g.,
      gamma proteobacteria), Megavirus retained all of the genomic features unique to
      Mimivirus, in particular its genes encoding key-elements of the translation
      apparatus, a trademark of cellular organisms. Besides homologs to the four
      aminoacyl-tRNA synthetases (aaRS) encoded by Mimivirus, Megavirus added three
      additional ones, raising the total of known virus-encoded aaRS to seven: IleRS,
      TrpRS, AsnRS, ArgRS, CysRS, MetRS, TyrRS. This finding strongly suggests that
      large DNA viruses derived from an ancestral cellular genome by reductive
      evolution. The nature of this cellular ancestor remains hotly debated.

PMID- 22482025
TI  - Protein misfolding and clearance in demyelinating peripheral neuropathies: 
      Therapeutic implications.
AB  - Peripheral neuropathies such as Charcot-Marie-Tooth disease (CMT) are a group of
      neurological disorders that affect the peripheral nervous system. Although
      demyelinating CMT is the most prevalent hereditary peripheral neuropathy, there
      are currently no effective treatments for patients suffering from this disease.
      Recent studies by our group and others have provided a link between protein
      misfolding and demyelinating CMT and indicate that impairment of the proteasome
      and aggresome-autophagy pathways may contribute to CMT pathogenesis. These
      studies suggest that targeting protein quality control systems involved in
      cytoprotection against CMT-associated misfolded proteins could have therapeutic
      benefits for treating demyelinating CMT.

PMID- 22482026
TI  - Biorenewables, the bio-based economy and sustainability.

PMID- 22482027
TI  - Next-generation cellulosic ethanol technologies and their contribution to a
      sustainable Africa.
AB  - The world is currently heavily dependent on oil, especially in the transport
      sector. However, rising oil prices, concern about environmental impact and supply
      instability are among the factors that have led to greater interest in renewable
      fuel and green chemistry alternatives. Lignocellulose is the only foreseeable
      renewable feedstock for sustainable production of transport fuels. The main
      technological impediment to more widespread utilization of lignocellulose for
      production of fuels and chemicals in the past has been the lack of low-cost
      technologies to overcome the recalcitrance of its structure. Both biological and
      thermochemical second-generation conversion technologies are currently coming
      online for the commercial production of cellulosic ethanol concomitantly with
      heat and electricity production. The latest advances in biological conversion of
      lignocellulosics to ethanol with a focus on consolidated bioprocessing are
      highlighted. Furthermore, integration of cellulosic ethanol production into
      existing bio-based industries also using thermochemical processes to optimize
      energy balances is discussed. Biofuels have played a pivotal yet suboptimal role
      in supplementing Africa's energy requirements in the past. Capitalizing on sub
      Saharan Africa's total biomass potential and using second-generation technologies
      merit a fresh look at the potential role of bioethanol production towards
      developing a sustainable Africa while addressing food security, human needs and
      local wealth creation.

PMID- 22482028
TI  - How can land-use modelling tools inform bioenergy policies?
AB  - Targets for bioenergy have been set worldwide to mitigate climate change.
      Although feedstock sources are often ambiguous, pledges in European nations, the
      United States and Brazil amount to more than 100 Mtoe of biorenewable fuel
      production by 2020. As a consequence, the biofuel sector is developing rapidly,
      and it is increasingly important to distinguish bioenergy options that can
      address energy security and greenhouse gas mitigation from those that cannot.
      This paper evaluates how bioenergy production affects land-use change (LUC), and
      to what extent land-use modelling can inform sound decision-making. We identified
      local and global internalities and externalities of biofuel development
      scenarios, reviewed relevant data sources and modelling approaches, identified
      sources of controversy about indirect LUC (iLUC) and then suggested a framework
      for comprehensive assessments of bioenergy. Ultimately, plant biomass must be
      managed to produce energy in a way that is consistent with the management of
      food, feed, fibre, timber and environmental services. Bioenergy production
      provides opportunities for improved energy security, climate mitigation and rural
      development, but the environmental and social consequences depend on feedstock
      choices and geographical location. The most desirable solutions for bioenergy
      production will include policies that incentivize regionally integrated
      management of diverse resources with low inputs, high yields, co-products,
      multiple benefits and minimal risks of iLUC. Many integrated assessment models
      include energy resources, trade, technological development and regional
      environmental conditions, but do not account for biodiversity and lack detailed
      data on the location of degraded and underproductive lands that would be ideal
      for bioenergy production. Specific practices that would maximize the benefits of
      bioenergy production regionally need to be identified before a global analysis of
      bioenergy-related LUC can be accomplished.

PMID- 22482029
TI  - Biofuels and land-use changes: searching for the top model.
AB  - The use of agricultural-based biofuels has expanded. Discussions on how to assess
      green house gas (GHG) emissions from biofuel policies, specifically on (non
      observed) land-use change (LUC) effects involve two main topics: (i) the
      limitations on the existing methodologies, and (ii) how to isolate the effects of
      biofuels. This paper discusses the main methodologies currently used by policy
      makers to take decisions on how to quantify LUCs owing to biofuel production
      expansion. It is our opinion that the concerns regarding GHG emissions associated
      with LUCs should focus on the agricultural sector as a whole rather than
      concentrating on biofuel production. Actually, there are several limitations of
      economic models and deterministic methodologies for simulating and explaining
      LUCs resulting from the expansion of the agricultural sector. However, it is
      equally true that there are avenues of possibilities to improve models and make
      them more accurate and precise in order to be used for policy-making. Models
      available need several improvements to reach perfection. Any top model requires a
      concentration of interdisciplinary designers in order to replicate empirical
      evidence and capture correctly the agricultural sector dynamics for different
      countries and regions. Forgetting those limitations means that models will be
      used for the wrong purposes.

PMID- 22482030
TI  - Can biofuels be a solution to climate change? The implications of land use change
      related emissions for policy.
AB  - Biofuels have gained increasing attention as an alternative to fossil fuels for
      several reasons, one of which is their potential to reduce the greenhouse gas
      (GHG) emissions from the transportation sector. Recent studies have questioned
      the validity of claims about the potential of biofuels to reduce GHG emissions
      relative to the liquid fossil fuels they are replacing when emissions owing to
      direct (DLUC) and indirect land use changes (ILUC) that accompany biofuels are
      included in the life cycle GHG intensity of biofuels. Studies estimate that the
      GHG emissions released from ILUC could more than offset the direct GHG savings by
      producing biofuels and replacing liquid fossil fuels and create a 'carbon debt'
      with a long payback period. The estimates of this payback period, however, vary
      widely across biofuels from different feedstocks and even for a single biofuel
      across different modelling assumptions. In the case of corn ethanol, this payback
      period is found to range from 15 to 200 years. We discuss the challenges in
      estimating the ILUC effect of a biofuel and differences across biofuels, and its
      sensitivity to the assumptions and policy scenarios considered by different
      economic models. We also discuss the implications of ILUC for designing policies
      that promote biofuels and seek to reduce GHG emissions. In a first-best setting,
      a global carbon tax is needed to set both DLUC and ILUC emissions to their
      optimal levels. However, it is unclear whether unilateral GHG mitigation
      policies, even if they penalize the ILUC-related emissions, would increase social
      welfare and lead to optimal emission levels. In the absence of a global carbon
      tax, incentivizing sustainable land use practices through certification
      standards, government regulations and market-based pressures may be a viable
      option for reducing ILUC.

PMID- 22482031
TI  - Contrasts and synergies in different biofuel reports.
AB  - The societal debate on biofuels is characterised by increased complexity. This
      can hinder the effective governance of the field. This paper attempts a
      quantitative bird's eye meta-analysis of this complexity by mapping different
      stakeholder perspectives and expected outcomes as seen in the secondary
      literature on biofuels, along the lines of the People-Planet-Profit framework.
      Our analysis illustrates the tension between stated and actual drivers of large
      scale biofuel development, especially for first generation biofuels. Although
      environmental (Planet) aspects have dominated the biofuel debate, their overall
      assessment is mostly negative with regard to first generation biofuels. By
      contrast, economic (Profit) aspects are the only ones that are assessed
      positively with regard to first generation biofuels. Furthermore, positive and
      negative assessments of biofuel development are strongly influenced by the
      differences in focus between different stakeholder clusters. Stakeholders who
      appear generally supportive to biofuel development (industry) focus relatively
      more on aspects that are generally assessed as positive (Profit). By contrast,
      non-supportive stakeholders (NGO's) tend to focus mainly on aspects that are
      generally assessed as negative (Planet). Moreover, our analysis of reference
      lists revealed few citations of primary scientific data, and also that
      intergovernmental organizations produce the most influential publications in the
      debate. The surprising lack of listed references to scientific (primary) data
      reveals a need to assess in which arena the transition of scientific data towards
      secondary publications takes place, and how one can measure its quality. This
      work should be understood as a first effort to take some control over a complex
      and contradictory number of publications, and to allow the effective governance
      of the field through the identification of areas of overlapping consensus and
      persisting controversy, without reverting to claims on technical detail.

PMID- 22482032
TI  - Multi-scale process and supply chain modelling: from lignocellulosic feedstock to
      process and products.
AB  - There is a large body of literature regarding the choice and optimization of
      different processes for converting feedstock to bioethanol and bio-commodities;
      moreover, there has been some reasonable technological development in
      bioconversion methods over the past decade. However, the eventual cost and other
      important metrics relating to sustainability of biofuel production will be
      determined not only by the performance of the conversion process, but also by the
      performance of the entire supply chain from feedstock production to consumption.
      Moreover, in order to ensure world-class biorefinery performance, both the
      network and the individual components must be designed appropriately, and
      allocation of resources over the resulting infrastructure must effectively be
      performed. The goal of this work is to describe the key challenges in bioenergy
      supply chain modelling and then to develop a framework and methodology to show
      how multi-scale modelling can pave the way to answer holistic supply chain
      questions, such as the prospects for second generation bioenergy crops.

PMID- 22482033
TI  - An assessment of the potential of drylands in eight sub-Saharan African countries
      to produce bioenergy feedstocks.
AB  - This paper synthesizes lessons learnt from research that aimed to identify land
      in the dryland regions of eight sub-Saharan African study countries where
      bioenergy feedstocks production has a low risk of detrimental environmental and
      socio-economic effects. The methodology involved using geographical information
      systems (GISs) to interrogate a wide range of datasets, aerial photograph and
      field verification, an extensive literature review, and obtaining information
      from a wide range of stakeholders. The GIS work revealed that Africa's drylands
      potentially have substantial areas available and agriculturally suitable for
      bioenergy feedstocks production. The other work showed that land-use and biomass
      dynamics in Africa's drylands are greatly influenced by the inherent
      'disequilibrium' behaviour of these environments. This behaviour challenges the
      sustainability concept and perceptions regarding the drivers, nature and
      consequences of deforestation, land degradation and other factors. An assessment
      of the implications of this behaviour formed the basis for the practical guidance
      suggested for bioenergy feedstock producers and bioenergy policy makers.

PMID- 22482034
TI  - Quantifying the advantage of looking forward.
AB  - We introduce a future orientation index to quantify the degree to which Internet
      users worldwide seek more information about years in the future than years in the
      past. We analyse Google logs and find a striking correlation between the
      country's GDP and the predisposition of its inhabitants to look forward.

PMID- 22482035
TI  - Amylases without known homologues discovered in an acid mine drainage:
      significance and impact.
AB  - Acid Mine Drainages (AMDs) are extreme environments characterized by acidic and
      oligotrophic conditions and by metal contaminations. A function-based screening
      of an AMD-derived metagenomic library led to the discovery and partial
      characterization of two non-homologous endo-acting amylases sharing no sequence
      similarity with any known amylase nor glycosidase. None carried known amylolytic
      domains, nor could be assigned to any GH-family. One amylase displayed no
      similarity with any known protein, whereas the second one was similar to TraC
      proteins involved in the bacterial type IV secretion system. According to the
      scarce similarities with known proteins, 3D-structure modelling using I-TASSER
      was unsuccessful. This study underlined the utility of a function-driven
      metagenomic approach to obtain a clearer image of the bacterial community
      enzymatic landscape. More generally, this work points out that screening for
      microorganisms or biomolecules in a priori incongruous environments could provide
      unconventional and new exciting ways for bioprospecting.

PMID- 22482036
TI  - Paleolithic Contingent in Modern Japanese: Estimation and Inference using Genome
      wide Data.
AB  - The genetic origins of Japanese populations have been controversial. Upper
      Paleolithic Japanese, i.e. Jomon, developed independently in Japanese islands for
      more than 10,000 years until the isolation was ended with the influxes of
      continental immigrants about 2,000 years ago. However, the knowledge of origin of
      Jomon and its contribution to the genetic pool of contemporary Japanese is still
      limited, albeit the extensive studies using mtDNA and Y chromosomes. In this
      report, we aimed to infer the origin of Jomon and to estimate its contribution to
      Japanese by fitting an admixture model with missing data from Jomon to a genome
      wide data from 94 worldwide populations. Our results showed that the genetic
      contributions of Jomon, the Paleolithic contingent in Japanese, are 54.3~62.3% in
      Ryukyuans and 23.1~39.5% in mainland Japanese, respectively. Utilizing inferred
      allele frequencies of the Jomon population, we further showed the Paleolithic
      contingent in Japanese had a Northeast Asia origin.

PMID- 22482037
TI  - Refractive Development in the "ROP Rat".
AB  - Although retinopathy of prematurity (ROP) is clinically characterized by abnormal
      retinal vessels at the posterior pole of the eye, it is also commonly
      characterized by vascular abnormalities in the anterior segment, visual
      dysfunction which is based in retinal dysfunction, and, most commonly of all,
      arrested eye growth and high refractive error, particularly (and paradoxically)
      myopia. The oxygen-induced retinopathy rat model of ROP presents neurovascular
      outcomes similar to the human disease, although it is not yet known if the "ROP
      rat" also models the small-eyed myopia characteristic of ROP. In this study,
      magnetic resonance images (MRIs) of albino (Sprague-Dawley) and pigmented (Long
      Evans) ROP rat eyes, and age- and strain-matched room-air-reared (RAR) controls,
      were examined. The positions and curvatures of the various optical media were
      measured and the refractive state (Px) of each eye estimated based on a
      previously published model. Even in adulthood (postnatal day 50), Sprague-Dawley
      and Long-Evans ROP rats were significantly myopic compared to strain-matched
      controls. The myopia in the Long-Evans ROP rats was more severe than in the
      Sprague-Dawley ROP rats, which also had significantly shorter axial lengths.
      These data reveal the ROP rat to be a novel and potentially informative approach
      to investigating physiological mechanisms in myopia in general and the myopia
      peculiar to ROP in particular.

PMID- 22482038
TI  - Beneficial effects of long-term administration of an oral formulation of
      Angiotensin-(1-7) in infarcted rats.
AB  - In this study was evaluated the chronic cardiac effects of a formulation
      developed by including angiotensin(Ang)-(1-7) in hydroxypropyl beta-cyclodextrin
      (HPbetaCD), in infarcted rats. Myocardial infarction (MI) was induced by left
      coronary artery occlusion. HPbetaCD/Ang-(1-7) was administered for 60 days (76
      MUg/Kg/once a day/gavage) starting immediately before infarction.
      Echocardiography was utilized to evaluate usual cardiac parameters, and radial
      strain method was used to analyze the velocity and displacement of myocardial
      fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was
      utilized to evaluate the fibrotic signaling involved in the remodeling process.
      Once-a-day oral HPbetaCD/Ang-(1-7) administration improved the cardiac function
      and reduced the deleterious effects induced by MI on TGF-beta and collagen type I
      expression, as well as on the velocity and displacement of myocardial fibers.
      These findings confirm cardioprotective effects of Ang-(1-7) and indicate
      HPbetaCD/Ang-(1-7) as a feasible formulation for long-term oral administration of
      this heptapeptide.

PMID- 22482039
TI  - The biological significance of evolution in autoimmune phenomena.
AB  - It is an inherent part of living to be in constant modification, which are due to
      answers resulting from environmental changes. The different systems make
      adaptations based on natural selection. With respect to the immune system of
      mammals, these changes have a lot to do with the interactions that occur
      continuously with other living species, especially microorganisms. The immune
      system is primarily designed to defend from germs and this response triggers
      inflammatory reactions which must be regulated in order not to generate damage to
      healthy tissue. The regulatory processes were added over time to prevent such
      damage. Through evolution the species have stored "an immunological experience,"
      which provides information that is important for developing effective responses
      in the future. The human species, which is at a high level of evolutionary
      immunological accumulation, have multiple immune defense strategies which, in
      turn, are highly regulated. Imbalances in these can result in autoimmunity."There
      is nothing permanent except change."(Heraclitus).

PMID- 22482040
TI  - Traditional dietary recommendations for the prevention of cardiovascular disease:
      do they meet the needs of our patients?
AB  - THE CHARACTERISTICS OF PATIENTS WITH CVD HAVE CHANGED: whereas smoking prevalence
      declines, obesity and metabolic syndrome are on the rise. Unfortunately, the
      traditional low-fat diet for the prevention of cardiovascular disease (CVD) still
      seems to be the "mainstream knowledge" despite contradicting evidence. But
      lowering LDL-cholesterol by the wrong diet even may be counterproductive, if sd
      LDL is raised and HDL is lowered. New insights into the pathophysiology of
      insulin resistance and its influence on the effects of dietary changes have led
      to a better approach: (1) the higher a patient's insulin resistance, the more
      important is the glycemic load of the diet. (2) Fat quality is much more
      important than fat quantity. (3) The best principle for a reduced calorie intake
      is not fat counting, but a high volume diet with low energy density, which means
      fibre rich vegetables and fruits. (4) And finally, satiation and palatability of
      a diet is very important: there is no success without the patient's compliance.
      Thus, the best approach to the dietary prevention of CVD is a Mediterranean style
      low-carb diet represented in the LOGI pyramid. Dietary guidelines for the
      prevention of CVD should to be revised accordingly.

PMID- 22482041
TI  - Abdominal decompression in children.
AB  - Abdominal compartment syndrome (ACS) increases the risk for mortality in
      critically ill children. It occurs in association with a wide variety of medical
      and surgical diagnoses. Management of ACS involves recognizing the development of
      intra-abdominal hypertension (IAH) by intra-abdominal pressure (IAP) monitoring,
      treating the underlying cause, and preventing progression to ACS by lowering IAP.
      When ACS is already present, supporting dysfunctional organs and decreasing IAP
      to prevent new organ involvement become an additional focus of therapy. Medical
      management strategies to achieve these goals should be employed but when medical
      management fails, timely abdominal decompression is essential to reduce the risk
      of mortality. A literature review was performed to understand the role and
      outcomes of abdominal decompression among children with ACS. Abdominal
      decompression appears to have a positive effect on patient survival. However,
      prospective randomized studies are needed to fully understand the indications and
      impact of these therapies on survival in children.

PMID- 22482043
TI  - Manipulation of the complement system for benefit in sepsis.
AB  - There is evidence in sepsis, both in rodents and in humans, that activation of
      the complement system results in excessive production of C5a, which triggers a
      series of events leading to septic shock, multiorgan failure, and lethality. In
      rodents following cecal ligation and puncture (CLP), which induces polymicrobial
      sepsis, in vivo blockade of C5a using neutralizing antibodies dramatically
      improved survival, reduced apoptosis of lymphoid cells, and attenuated the
      ensuing coagulopathy. Based on these data, it seems reasonable to consider
      therapeutic blockade of C5a in humans entering into sepsis and septic shock.
      Strategies for the development of such an antibody for use in humans are
      presented.

PMID- 22482042
TI  - Stimulators and activators of soluble guanylate cyclase: review and potential
      therapeutic indications.
AB  - The heme-protein soluble guanylyl cyclase (sGC) is the intracellular receptor for
      nitric oxide (NO). sGC is a heterodimeric enzyme with alpha and beta subunits and
      contains a heme moiety essential for binding of NO and activation of the enzyme.
      Stimulation of sGC mediates physiologic responses including smooth muscle
      relaxation, inhibition of inflammation, and thrombosis. In pathophysiologic
      states, NO formation and bioavailability can be impaired by oxidative stress and
      that tolerance to NO donors develops with continuous use. Two classes of
      compounds have been developed that can directly activate sGC and increase cGMP
      formation in pathophysiologic conditions when NO formation and bioavailability
      are impaired or when NO tolerance has developed. In this report, we review
      current information on the pharmacology of heme-dependent stimulators and heme
      independent activators of sGC in animal and in early clinical studies and the
      potential role these compounds may have in the management of cardiovascular
      disease.

PMID- 22482044
TI  - Thrombomodulin: a bifunctional modulator of inflammation and coagulation in
      sepsis.
AB  - Deregulated interplay between inflammation and coagulation plays a pivotal role
      in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target
      both inflammation and coagulation hold great promise for the treatment of sepsis.
      Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with
      protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the
      endothelial microenvironment in an anti-inflammatory and anticoagulant state. A
      recombinant soluble form of thrombomodulin has been approved to treat patients
      suffering from disseminated intravascular coagulation (DIC) and has thus far
      shown greater therapeutic potential than heparin. A phase II clinical trial is
      currently underway in the USA to study the efficacy of thrombomodulin for the
      treatment of sepsis with DIC complications. This paper focuses on the critical
      roles that thrombomodulin plays at the intersection of inflammation and
      coagulation and proposes the possible existence of interactions with integrins
      via protein C. Finally, we provide a rationale for the clinical application of
      thrombomodulin for alleviating sepsis.

PMID- 22482046
TI  - Harmonic scalpel compared to conventional hemostasis in thyroid surgery: a meta
      analysis of randomized clinical trials.
AB  - Background. The study's aim was to determine whether conventional hemostasis (CH)
      or the Harmonic Scalpel (HS) results in shorter operative times for thyroidectomy
      and to evaluate the incidence of postoperative complications with each approach.
      Methods. A literature search was conducted from study inception to September 30,
      2008. Included studies randomized thyroidectomy patients to either CH or HS and
      reported the incidence of postoperative transient recurrent laryngeal nerve
      dysfunction (RLND) and hypocalcemia. Results. Nine RCTs were included. Use of the
      HS reduced operative time by 23.1 minutes (95% CI = 13.8, 32.33). There was no
      difference in the incidence of transient RLND (RR = 1.25, 95% CI = .56, 2.76),
      but a lower rate of transient hypocalcemia with the use of the HS (RR = .69, 95%
      CI = .51, .92). Conclusions. The use of HS in thyroidectomy significantly reduces
      operative time and is associated with a reduction in postoperative hypocalcemia
      compared to CH.

PMID- 22482045
TI  - Myocardial dysfunction in sepsis: a large, unsolved puzzle.
AB  - Sepsis has high incidence and mortality rates around the world. The role of
      cardiac depression in myocardial dysfunction during sepsis remains to be
      elucidated. This review attempts to summarize our understanding of the
      anatomical, histopathological, and pathophysiological mechanisms behind cardiac
      dysfunction. Biomarkers to detect cardiac depression have been used to recognize
      developing problems, but the actual impact of these tools remains unclear.

PMID- 22482047
TI  - Single-port laparoscopic spleen preserving distal pancreatectomy.
AB  - Single-port laparoscopic surgery has become increasingly popular, with widened
      indication to more types of surgery. This report will present our initial
      experience with spleen-preserving distal pancreatectomy technique through a small
      transumbilical incision using the single-port approach for a cystic tumor of
      pancreatic body. The surgery was done using specialized single-port instruments
      and normal laparoscopic instruments. The total operative time for this surgery is
      233 minutes, and it was completed without drains. Patient was discharged from the
      hospital on the third day postoperatively in good condition.

PMID- 22482048
TI  - Patient perceptions of natural orifice translumenal surgery.
AB  - Natural orifice translumenal endoscopic surgery (NOTES) is on the forefront of
      surgical technique, but existing research has produced mixed results regarding
      factors associated with interest in the procedure. Our objective was to ascertain
      patient opinions at a Canadian centre regarding scarless surgery. A survey
      comprising demographic data (gender, age, body mass index [BMI]), interest in
      NOTES, impact of increased risk, as well as importance of further research and
      shorter recovery time was administered to volunteer patients at outpatient
      general surgery clinics. Nonparametric tests were utilized to examine difference
      in response by age, sex, BMI, and preexisting scars. Of the 335 participants (57%
      female, mean age of 54.5 +/- 15.9 years, mean BMI of 28.7 +/- 6.9), the majority
      (83%) showed some interest, but this dropped to 38% when additional risk was
      factored in. Generally, women, those under 50 years of age and those of healthy
      weight, were more interested than male, older, and/or heavier patients. Most felt
      that research into NOTES and reduced length of inpatient stay were important (80%
      and 95%, respectively). Further investigation into objective NOTES outcomes are
      needed to provide patients adequate data to make an informed choice regarding
      surgical route.

PMID- 22482049
TI  - Fibromyalgia as a disorder related to distress and its therapeutic implications.

PMID- 22482050
TI  - Chemotherapy-induced oesophageal stricture in a child with osteosarcoma: a case
      report.
AB  - Treatment with a combination of chemotherapy and radiotherapy is known to be
      associated with oesophageal stricture in both children and adults with
      malignancies. However, oesophageal stricture resulting from chemotherapy alone is
      a rare complication, with few reports on it. We experienced a rare paediatric
      case of oesophageal stricture caused by chemotherapy for osteosarcoma of the left
      distal femur. After completion of the chemotherapy course, the patient showed
      dysphagia caused by the oesophageal stricture and underwent balloon dilatation
      for the oesophageal stricture. After balloon dilatation, he was able to ingest
      solid foods, and the oesophagus was normal without any strictures at the last
      follow-up (20 months after ballooning). Therefore, oesophageal stricture should
      be considered as a complication of treatment with chemotherapy alone in children
      with malignancies.

PMID- 22482051
TI  - Clear-cell adenocarcinoma of vesical origin: a case study of metastatic disease
      treated with chemotherapy.
AB  - Vesical clear cell adenocarcinoma is an uncommon tumour. The description of
      nearly all published cases focuses on histological issues, providing few clinical
      particulars and limited followup. The treatment choice is resection. No
      publications have been found regarding systemic treatments for advanced disease.
      We present a case of metastatic clear cell adenocarcinoma of the bladder treated
      with chemotherapy.

PMID- 22482052
TI  - From Cisplatin-Containing Sequential Radiochemotherapy towards Concurrent
      Treatment for Patients with Inoperable Locoregional Non-Small Cell Lung Cancer:
      Still Unanswered Questions.
AB  - Radiotherapy has been the mainstay of the treatment of stage III non-small cell
      lung cancer (NSCLC) patients. In the early nineties, combined treatment with
      chemotherapy was introduced. In 1995, a meta-analysis showed improved treatment
      outcome of the sequential use of radiochemotherapy (RCT) compared to radiotherapy
      alone, provided cisplatin was part of the chemotherapy course. Concurrent RCT
      compared to radiotherapy only yielded the same improvements of 4% in the 2-year
      and 2% in the 5-year overall survival rates. Just recently, two meta-analyses
      demonstrated that concurrent RCT is definitely superior to sequential RCT in
      terms of local control and 2-, 3-, and 5-year survival. However, several
      unanswered questions remain concerning the optimal chemotherapy regimen and
      radiotherapy doses and techniques in terms of treatment outcome and toxicity
      profile. Arguments supporting a daily low-dose cisplatin scheme are presented
      because of comparable radiosensitizing characteristics and favourable side
      effects. Increasing radiotherapy doses applied according to up-to-date techniques
      and combinations with new biologicals might lead to further treatment
      improvements.

PMID- 22482053
TI  - Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV
      Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?
AB  - Chemotherapy regimens may have differential efficacy by histology in nonsmall
      cell lung cancer (NSCLC). We examined the impact of histology on survival of
      patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line
      cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a
      taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997
      2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months
      and 8.1 months, respectively (P = .018). No statistically significant difference
      was observed in survival between C/C+G and C/C+T in both histologies. Adjusting
      for clinical and demographic characteristics, the effect of treatment regimen on
      survival did not differ by histology (P for interaction = .257). There was no
      statistically significant difference in hazard of death by histology in both
      groups. These results contrast the predictive role of histology and improved
      survival outcomes observed for cisplatin-pemetrexed regimens in advanced
      nonsquamous NSCLC.

PMID- 22482054
TI  - Healthcare costs and workloss burden of patients with chemotherapy-associated
      peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung
      cancer.
AB  - Objective. Chemotherapy-associated peripheral neuropathy (CAPN) is a painful side
      effect of chemotherapy. This study assesses healthcare and workloss costs of CAPN
      patients with breast, ovarian, head/neck, or non-small cell lung cancer (NSCLC)
      from a third-party payor/employer perspective. Research Design and Methods.
      Patients with qualifying tumors, and claims for chemotherapy and services
      indicative of peripheral neuropathy (PN) within 9-months of chemotherapy (cases)
      were identified in a administrative claims database. Cases were matched 1 : 1 to
      controls with no PN-related claims based on demographics, diabetes history and
      propensity for having a diagnosis of PN during the study period (based on
      resource use and comorbidities in a 3-month baseline period). Average all-cause
      healthcare costs, resource use and workloss burden were determined. Results.
      Average healthcare costs were $17,344 higher for CAPN cases than their non-CAPN
      controls, with outpatient costs being the highest component (with cases having
      excess costs of $8,092). On average, each CAPN case had 12 more outpatient visits
      than controls, and spent more days in the hospital. Workloss burden was higher
      for cases but not statistically different from controls. Conclusion. This study
      establishes that breast, ovarian, head/neck, or NSCLC patients with CAPN have
      significant excess healthcare costs and resource use.

PMID- 22482056
TI  - The diversity of endophytic methylotrophic bacteria in an oil-contaminated and an
      oil-free mangrove ecosystem and their tolerance to heavy metals.
AB  - Methylobacterium strains were isolated from mangrove samples collected in
      Bertioga, SP, Brazil, from locations either contaminated or uncontaminated by oil
      spills. The tolerances of the strains to different heavy metals were assessed by
      exposing them to different concentrations of cadmium, lead, and arsenic (0.1 mM,
      0.5 mM, 1 mM, 2 mM, 4 mM, and 8 mM). Additionally, the genetic diversity of
      Methylobacterium spp. was determined by sequence analysis of the 16S rRNA genes.
      The isolates from the contaminated locations were grouped, suggesting that oil
      can select for microorganisms that tolerate oil components and can change the
      methylotrophic bacterial community. Cadmium is the most toxic heavy metal
      assessed in this work, followed by arsenic and lead, and two isolates of
      Methylobacterium were found to be tolerant to all three metals. These isolates
      have the potential to bioremediate mangrove environments contaminated by oil
      spills by immobilizing the heavy metals present in the oil.

PMID- 22482057
TI  - Breast axillary lymph node metastasis.

PMID- 22482055
TI  - Mitochondria death/survival signaling pathways in cardiotoxicity induced by
      anthracyclines and anticancer-targeted therapies.
AB  - Anthracyclines remain the cornerstone of treatment in many malignancies but these
      agents have a cumulative dose relationship with cardiotoxicity. Development of
      cardiomyopathy and congestive heart failure induced by anthracyclines are
      typically dose-dependent, irreversible, and cumulative. Although past studies of
      cardiotoxicity have focused on anthracyclines, more recently interest has turned
      to anticancer drugs that target many proteins kinases, such as tyrosine kinases.
      An attractive model to explain the mechanism of this cardiotoxicity could be
      myocyte loss through cell death pathways. Inhibition of mitochondrial transition
      permeability is a valuable tool to prevent doxorubicin-induced cardiotoxicity. In
      response to anthracycline treatment, activation of several protein kinases,
      neuregulin/ErbB2 signaling, and transcriptional factors modify mitochondrial
      functions that determine cell death or survival through the modulation of
      mitochondrial membrane permeability. Cellular response to anthracyclines is also
      modulated by a myriad of transcriptional factors that influence cell fate.
      Several novel targeted chemotherapeutic agents have been associated with a small
      but worrying risk of left ventricular dysfunction. Agents such as trastuzumab and
      tyrosine kinase inhibitors can lead to cardiotoxicity that is fundamentally
      different from that caused by anthracyclines, whereas biological effects converge
      to the mitochondria as a critical target.

PMID- 22482058
TI  - RKIP Suppresses Breast Cancer Metastasis to the Bone by Regulating Stroma
      Associated Genes.
AB  - In the past decade cancer research has recognized the importance of tumorstroma
      interactions for the progression of primary tumors to an aggressive and invasive
      phenotype and for colonization of new organs in the context of metastasis. The
      dialogue between tumor cells and the surrounding stroma is a complex and dynamic
      phenomenon, as many cell types and soluble factors are involved. While the
      function of many of the players involved in this cross talk have been studied,
      the regulatory mechanisms and signaling pathways that control their expression
      haven't been investigated in depth. By using a novel, interdisciplinary approach
      applied to the mechanism of action of the metastasis suppressor, Raf kinase
      inhibitory protein (RKIP), we identified a signaling pathway that suppresses
      invasion and metastasis through regulation of stroma-associated genes.
      Conceptually, the approach we developed uses a master regulator and expression
      arrays from breast cancer patients to formulate hypotheses based on clinical
      data. Experimental validation is followed by further bioinformatic analysis to
      establish the clinical significance of discoveries. Using RKIP as an example we
      show here that this multi-step approach can be used to identify gene regulatory
      mechanisms that affect tumor-stroma interactions that in turn influence
      metastasis to the bone or other organs.

PMID- 22482059
TI  - Active roles of tumor stroma in breast cancer metastasis.
AB  - Metastasis is the major cause of death for breast cancer patients. Tumors are
      heterogenous cellular entities composed of cancer cells and cells of the
      microenvironment in which they reside. A reciprocal dynamic interaction occurs
      between the tumor cells and their surrounding stroma under physiological and
      pathological conditions. This tumor-host communication interface mediates the
      escape of tumor cells at the primary site, survival of circulating cancer cells
      in the vasculature, and growth of metastatic cancer at secondary site. Each step
      of the metastatic process is accompanied by recruitment of stromal cells from the
      microenvironment and production of unique array of growth factors and chemokines.
      Stromal microenvironment may play active roles in breast cancer metastasis.
      Elucidating the types of cells recruited and signal pathways involved in the
      crosstalk between tumor cells and stromal cells will help identify novel
      strategies for cotargeting cancer cells and tumor stromal cells to suppress
      metastasis and improve patient outcome.

PMID- 22482060
TI  - The Microenvironmental Effect in the Progression, Metastasis, and Dormancy of
      Breast Cancer: A Model System within Bone Marrow.
AB  - Despite diagnostic advances, breast cancer remains the most prevalent cancer
      among women in the United States. The armamentarium of treatment options for
      metastatic disease is limited and mostly ineffective with regards to eradicating
      cancer. However, there have been novel findings in the recent literature that
      substantiate the function of the microenvironment in breast cancer progression
      and the support of metastasis to tertiary sites such as bone marrow. The
      uncovered significance of the microenvironment in the pathophysiology of breast
      cancer metastasis has served to challenge previously widespread theories and
      introduce new perspectives for the future research to eradicate breast cancer.
      This paper delineates the current understanding of the molecular mechanisms
      involved in the interactions between breast cancer cells and the microenvironment
      in progression, metastasis, and dormancy. The information, in addition to other
      mechanisms described in bone marrow, is discussed in the paper.

PMID- 22482062
TI  - Successful treatment of chronic osteomyelitis of the radius.
AB  - Chronic osteomyelitis is uncommon in the United Kingdom and Ireland. Current
      migration trends with an influx of people from less affluent nations may result
      in more cases of chronic osteomyelitis being seen in community and hospital
      practice. We report on a case of chronic osteomyelitis of the radius and document
      current treatment recommendations.

PMID- 22482061
TI  - Target points in trastuzumab resistance.
AB  - Epidermal growth factor (EGF) family of receptors is involved in cell growth and
      differentiation. The human EGF2 (HER2) lacks natural ligands, and correlation
      between HER2 levels and carcinogenesis makes the receptor an ideal candidate for
      targeted therapy in breast cancer. Trastuzumab is a humanized antibody applied
      against HER2-positive breast tumors in clinic. Metastatic tumors respond well to
      trastuzumab therapy for the first year, but development of antibody resistance
      helps the tumors to regrow allowing the disease to progress. Trastuzumab
      resistance is shaped via a range of intracellular signaling pathways that are
      interconnected and share in key effector molecules. Identification of a common
      node central to these resistance pathways could provide an ultimate solution for
      trastuzumab resistance in breast and other cancers.

PMID- 22482063
TI  - Neonatal cyanosis: diagnostic and management challenges.
AB  - Neonatal central cyanosis is always a sign of serious pathological processes and
      may involve diverse organs and impose a significant diagnostic and therapeutic
      challenge. Here, we report an unusual presentation of Ebstein's anomaly, a rare
      congenital heart malformation, as the cause of central cyanosis in a one-week-old
      full-term infant. Initiation of PEG(1) therapy in neonates with Ebstein's anomaly
      always needs a very careful consideration because of a high risk for the
      development of a "circular shunt" leading to severe deterioration of multiple
      organs perfusion.

PMID- 22482064
TI  - Viral hepatitis: retrospective review in a canadian pediatric hospital.
AB  - Introduction. Clinical presentation of viral hepatitis ranges from mild symptoms
      to fulminant hepatitis. Our aim is to describe clinical presentation and outcomes
      of children with viral hepatitis from the Eastern Ontario/Western Quebec regions
      of Canada. Methods. Retrospective chart review of children diagnosed with viral
      hepatitis at our institution from January 1, 1998, to December 31, 2007. Results.
      There were 261 charts reviewed, only 64 had a confirmed viral etiology: 34 (53%)
      hepatitis B (HBV), 16 (25%) hepatitis C (HCV), 4 (6.3%) hepatitis A (HAV), 7
      (11%) cytomegalovirus (CMV), and 3 (4.7%) Epstein-Barr virus (EBV). Children with
      HBV presented at a mean age of 6.4 +/- 4.6 years. Spontaneous seroconversion
      (appearance of HBVeAb and loss of HBVeAg) occurred in 21/34 (61.7%). Children
      with acute hepatitis (HAV, CMV, and EBV) presented with mild abdominal pain,
      jaundice, and fevers. Overall outcome was excellent. Conclusion. Acute and
      chronic hepatitis in children has a benign course; moreover, HBV spontaneous
      seroconversion is common in pediatric patients.

PMID- 22482065
TI  - High-sensitivity C reactive protein: associations with cardiovascular risk
      factors and tracking in female adolescents and young adults.
AB  - Objective. We assessed adolescent anthropometry, lipids, insulin, glucose, and
      blood pressures to identify factors associated with high-sensitivity C-reactive
      protein (hsCRP) and its tracking in young adults. Methods. Ten-year prospective
      study of 589 schoolgirls, 321 black, 268 white. Results. HsCRP did not differ (P
      > .08) by race or oral contraceptive use. HsCRP tracked from age 16 to 25 (r =
      0.77), 16 to 26 (r = 0.50), 24 to 26 (r = 0.66), and 25 to 26 (r = 0.71), all P
      <= .02. By stepwise regression, at age 16, waist circumference accounted for
      44.8% of hsCRP variance; BMI accounted for 33.1%, 34.4%, and 31.1% at ages 24,
      25, and 26, P < .0001 for all. Changes in cholesterol and BMI were associated
      with change in hsCRP from age 24-26 (partial R(2) = 12.3%  P < .0001, 6.6%  P =
      .0012). Changes in BMI and triglyceride (partial R(2) = 8.5%  P = .0001, 3.3%, P
      = .0045) were associated with change in hsCRP from age 25 to 26. Conclusions.
      HsCRP tracks from age 16 to 26, with BMI, waist circumference, and cholesterol as
      major determinants.

PMID- 22482066
TI  - Clinical significance of auditive involvement in rheumatoid arthritis: a case
      control study.
AB  - Introduction. Rheumatoid arthritis (RA) can involve the incudomalleolar or
      incudostapedial articulations. Objective. To know the punctual prevalence of
      audiological alterations in patients with RA. Patients and Methods. RA patients
      and their controls (Cs), were evaluated by Tonal Audiometry (AU); if there were
      alterations in the air conduction (AC), bone conduction (BC), Logoaudiometry
      (LG), and Tympanometry (T) were performed. Results. 45 RA patients and 45 Cs were
      evaluated. RA patients had 40% of bilateral and 17.8% unilateral alteration
      versus Cs with 22.2% bilateral and 4.4% unilateral alteration versus Cs with
      22.2% bilateral and 4.4% unilateral in AC audiometry. In conventional T (CT) As
      type curves in patients with RA, there were 22 LE (48.8%) and 26 RE (57.7%)
      versus Cs, there were16 RE (35.5%) and 20 LE (44.4%). In High-frequency T (HFT):
      the 3B1G pattern in RA more frequent versus Controls (Cs) in RE (P = .002 and LE
      (P = .01). There were no differences according to RA activity or RA disease
      evolution. Conclusions. There is a greater tendency of auditive loss of As curves
      in CT (rigidity in ossicular chain) and of the 3B1G pattern in HFT in RA.

PMID- 22482067
TI  - Optimizing reliability of digital inclinometer and flexicurve ruler measures of
      spine curvatures in postmenopausal women with osteoporosis of the spine: an
      illustration of the use of generalizability theory.
AB  - The study illustrates the application of generalizability theory (G-theory) to
      identify measurement protocols that optimize reliability of two clinical methods
      for assessing spine curvatures in women with osteoporosis. Triplicate measures of
      spine curvatures were acquired for 9 postmenopausal women with spine osteoporosis
      by two raters during a single visit using a digital inclinometer and a flexicurve
      ruler. G-coefficients were estimated using a G-study, and a measurement protocol
      that optimized inter-rater and inter-trial reliability was identified using
      follow-up decision studies. The G-theory provides reliability estimates for
      measurement devices which can be generalized to different clinical contexts
      and/or measurement designs.

PMID- 22482068
TI  - Complement-4 deficiency in a child with systemic lupus erythematosus presenting
      with standard treatment-resistant severe skin lesion.
AB  - The complement system is of great importance in systemic lupus erythematosus.
      Complete genetically determined deficiencies are with few exceptions reported for
      the various complement proteins, and most of the deficiency states are rare.
      Deficiencies of the factors in the classical pathway are also associated with
      development SLE and SLE-like disorders. Most of the patients with lupus present
      skin involvement. Approximately, 75-95% of patients with cutaneous lupus
      erythematosus respond to antimalarial therapy and/or topical
      glucocorticosteroids. Immunosuppressive agents are usually considered a second
      line approach in patients with resistant disease. In this study, we present the
      clinical features and determine the molecular basis responsible for the complete
      C4A and C4B deficiencies in a lupus patient presented subacute cutaneous lupus
      erythematosus and resistance to treatment.

PMID- 22482070
TI  - A two-study comparison of clinical and MRI markers of transition from mild
      cognitive impairment to Alzheimer's disease.
AB  - A published predictor model in a single-site cohort study (questionable dementia,
      QD) that contained episodic verbal memory (SRT total recall), informant report of
      function (FAQ), and MRI measures was tested using logistic regression and ROC
      analyses with comparable measures in a second multisite cohort study (Alzheimer's
      Disease Neuroimaging Initiative, ADNI). There were 126 patients in QD and 282
      patients in ADNI with MCI followed for 3 years. Within each sample, the
      differences in AUCs between the statistical models were very similar. Adding
      hippocampal and entorhinal cortex volumes to the model containing AVLT/SRT, FAQ,
      age and MMSE increased the area under the curve (AUC) in ADNI but not QD, with
      sensitivity increasing by 2% in ADNI and 2% in QD for a fixed specificity of 80%.
      Conversely, adding episodic verbal memory (SRT/AVLT) and FAQ to the model
      containing age, Mini Mental State Exam (MMSE), hippocampal and entorhinal cortex
      volumes increased the AUC in ADNI and QD, with sensitivity increasing by 17% in
      ADNI and 10% in QD for 80% specificity. The predictor models showed similar
      differences from each other in both studies, supporting independent validation.
      MRI hippocampal and entorhinal cortex volumes showed limited added predictive
      utility to memory and function measures.

PMID- 22482069
TI  - MicroRNAs in Postischemic Vascular Repair.
AB  - The term angiogenesis describes the growth of endothelial sprouts from
      preexisting postcapillary venules. More recently, this term has been used to
      generally indicate the growth and remodeling process of the primitive vascular
      network into a complex network during development. In adulthood, angiogenesis is
      activated as a reparative process during wound healing and following ischemia,
      and it plays a key role in tumor growth and metastasis as well as in inflammatory
      diseases and diabetic retinopathy. MicroRNAs (miRNAs) are endogenous, small,
      noncoding RNAs that negatively control gene expression of target mRNAs. In this
      paper, we aim at describing the role of miRNAs in postischemic angiogenesis.
      First, we will describe the regulation and the expression of miRNAs in
      endothelial cells. Then, we will analyze the role of miRNAs in postischemic
      vascular repair. Finally, we will discuss the role of circulating miRNAs as
      potential biomarkers in ischemic diseases.

PMID- 22482071
TI  - Automated VOI Analysis in FDDNP PET Using Structural Warping: Validation through
      Classification of Alzheimer's Disease Patients.
AB  - We evaluate an automated approach to the cortical surface mapping (CSM) method of
      VOI analysis in PET. Although CSM has been previously shown to be successful, the
      process can be long and tedious. Here, we present an approach that removes these
      difficulties through the use of 3D image warping to a common space. We test this
      automated method using studies of FDDNP PET in Alzheimer's disease and mild
      cognitive impairment. For each subject, VOIs were created, through CSM, to
      extract regional PET data. After warping to the common space, a single set of CSM
      generated VOIs was used to extract PET data from all subjects. The data extracted
      using a single set of VOIs outperformed the manual approach in classifying AD
      patients from MCIs and controls. This suggests that this automated method can
      remove variance in measurements of PET data and can facilitate accurate, high
      throughput image analysis.

PMID- 22482073
TI  - Stimulation-dependent intraspinal microtubules and synaptic failure in
      Alzheimer's disease: a review.
AB  - There are many microtubules in axons and dendritic shafts, but it has been
      thought that there were fewer microtubules in spines. Recently, there have been
      four reports that observed the intraspinal microtubules. Because microtubules
      originate from the centrosome, these four reports strongly suggest a stimulation
      dependent connection between the nucleus and the stimulated postsynaptic membrane
      by microtubules. In contrast, several pieces of evidence suggest that spine
      elongation may be caused by the polymerization of intraspinal microtubules. This
      structural mechanism for spine elongation suggests, conversely, that the synapse
      loss or spine loss observed in Alzheimer's disease may be caused by the
      depolymerization of intraspinal microtubules. Based on this evidence, it is
      suggested that the impairment of intraspinal microtubules may cause spinal
      structural change and block the translocation of plasticity-related molecules
      between the stimulated postsynaptic membranes and the nucleus, resulting in the
      cognitive deficits of Alzheimer's disease.

PMID- 22482072
TI  - Genomics of Dementia: APOE- and CYP2D6-Related Pharmacogenetics.
AB  - Dementia is a major problem of health in developed societies. Alzheimer's disease
      (AD), vascular dementia, and mixed dementia account for over 90% of the most
      prevalent forms of dementia. Both genetic and environmental factors are
      determinant for the phenotypic expression of dementia. AD is a complex disorder
      in which many different gene clusters may be involved. Most genes screened to
      date belong to different proteomic and metabolomic pathways potentially affecting
      AD pathogenesis. The epsilon4 variant of the APOE gene seems to be a major risk
      factor for both degenerative and vascular dementia. Metabolic factors,
      cerebrovascular disorders, and epigenetic phenomena also contribute to
      neurodegeneration. Five categories of genes are mainly involved in
      pharmacogenomics: genes associated with disease pathogenesis, genes associated
      with the mechanism of action of a particular drug, genes associated with phase I
      and phase II metabolic reactions, genes associated with transporters, and
      pleiotropic genes and/or genes associated with concomitant pathologies. The APOE
      and CYP2D6 genes have been extensively studied in AD. The therapeutic response to
      conventional drugs in patients with AD is genotype specific, with CYP2D6-PMs,
      CYP2D6-UMs, and APOE-4/4 carriers acting as the worst responders. APOE and CYP2D6
      may cooperate, as pleiotropic genes, in the metabolism of drugs and hepatic
      function. The introduction of pharmacogenetic procedures into AD pharmacological
      treatment may help to optimize therapeutics.

PMID- 22482074
TI  - Amyloid Beta and tau proteins as therapeutic targets for Alzheimer's disease
      treatment: rethinking the current strategy.
AB  - Alzheimer's disease (AD) is defined by the concurrence of accumulation of
      abnormal aggregates composed of two proteins: Amyloid beta (Abeta) and tau, and
      of cellular changes including neurite degeneration and loss of neurons and
      cognitive functions. Based on their strong association with disease, genetically
      and pathologically, it is not surprising that there has been a focus towards
      developing therapies against the aggregated structures. Unfortunately, current
      therapies have but mild benefit. With this in mind we will focus on the
      relationship of synaptic plasticity with Abeta and tau protein and their role as
      potential targets for the development of therapeutic drugs. Finally, we will
      provide perspectives in developing a multifactorial strategy for AD treatment.

PMID- 22482075
TI  - Analyzing microarray data of Alzheimer's using cluster analysis to identify the
      biomarker genes.
AB  - Alzheimer is characterized by the presence of senile plaques and neurofibrillary
      tangles in cortical regions of the brain. The experimental data is taken from
      Gene Expression Omnibus. A hierarchical Cluster analysis and TreeView were
      performed to group genes on the basis of the expression pattern. The dynamic
      change of expression over time and diverse patterns of expression support the
      concept of a complex local milieu. TreeView allows the organized data to be
      visualized. List of 24 genes were obtained which showed high expression levels.
      Three genes, SORL1, APP, and APOE, are suspected to cause Alzheimer's whereas the
      other 21 genes are related to other diseases but may also be found to be
      associated with Alzheimer's, and these are TMEM59, CCT4, IGF2R, SFPQ, PRDX3,
      RNF14, IDS, SSBP1, SYNE2, TXNL4A, STXBP3, SMARCB1, ULK2, AGTPBP1, FABP7, CALB1,
      H2AFY, COPA, SAP18, ATIC and SYNCRIP.

PMID- 22482076
TI  - Affective learning and psychophysiological reactivity in dementia patients.
AB  - We examined the association of faces with biographical information that varied in
      emotional content in patients with Alzheimer's disease and a healthy control
      group. During two experimental sessions, participants rated neutral male faces on
      dimensions of hedonic valence and emotional arousal, later paired with fictitious
      biographical information. Both groups changed their ratings of the faces
      according to the biographical content. Free recall and recognition were tested in
      the second session. Patients neither recalled the biographical information nor
      recognized the faces, whereas the controls did. In addition, psychophysiological
      measures were taken in response to the face stimuli. Patients showed significant
      heart rate modulation as a function of their emotion ratings, whereas the
      controls did not. No correlation of rating changes with skin conductance was
      found in any group. Results suggest that psychophysiological reactions such as
      heart rate changes may indicate preserved affective associative learning in
      dementia patients despite impaired explicit memory.

PMID- 22482077
TI  - Shilajit: a natural phytocomplex with potential procognitive activity.
AB  - Shilajit is a natural substance found mainly in the Himalayas, formed for
      centuries by the gradual decomposition of certain plants by the action of
      microorganisms. It is a potent and very safe dietary supplement, restoring the
      energetic balance and potentially able to prevent several diseases. Recent
      investigations point to an interesting medical application toward the control of
      cognitive disorders associated with aging, and cognitive stimulation. Thus,
      fulvic acid, the main active principle, blocks tau self-aggregation, opening an
      avenue toward the study of Alzheimer's therapy. In essence, this is a
      nutraceutical product of demonstrated benefits for human health. Considering the
      expected impact of shilajit usage in the medical field, especially in the
      neurological sciences, more investigations at the basic biological level as well
      as clinical trials are necessary, in order to understand how organic molecules of
      shilajit and particularly fulvic acid, one of the active principles, and
      oligoelements act at both the molecular and cellular levels and in the whole
      organism.

PMID- 22482078
TI  - The Complexity of Sporadic Alzheimer's Disease Pathogenesis: The Role of RAGE as
      Therapeutic Target to Promote Neuroprotection by Inhibiting Neurovascular
      Dysfunction.
AB  - Alzheimer's disease (AD) is the most common cause of dementia. Amyloid plaques
      and neurofibrillary tangles are prominent pathological features of AD. Aging and
      age-dependent oxidative stress are the major nongenetic risk factors for AD. The
      beta-amyloid peptide (Abeta), the major component of plaques, and advanced
      glycation end products (AGEs) are key activators of plaque-associated cellular
      dysfunction. Abeta and AGEs bind to the receptor for AGEs (RAGE), which transmits
      the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF
      kappaB). RAGE-mediated signaling is an important contributor to neurodegeneration
      in AD. We will summarize the current knowledge and ongoing studies on RAGE
      function in AD. We will also present evidence for a novel pathway induced by RAGE
      in AD, which leads to the expression of thioredoxin interacting protein (TXNIP),
      providing further evidence that pharmacological inhibition of RAGE will promote
      neuroprotection by blocking neurovascular dysfunction in AD.

PMID- 22482079
TI  - Silencing of amyloid precursor protein expression using a new engineered delta
      ribozyme.
AB  - Alzheimer's disease (AD) etiological studies suggest that an elevation in amyloid
      beta peptides (Abeta) level contributes to aggregations of the peptide and
      subsequent development of the disease. The major constituent of these amyloid
      peptides is the 1 to 40-42 residue peptide (Abeta(40-42)) derived from amyloid
      protein precursor (APP). Most likely, reducing Abeta levels in the brain may
      block both its aggregation and neurotoxicity and would be beneficial for patients
      with AD. Among the several possible ways to lower Abeta accumulation in the
      cells, we have selectively chosen to target the primary step in the Abeta
      cascade, namely, to reduce APP gene expression. Toward this end, we engineered
      specific SOFA-HDV ribozymes, a new generation of catalytic RNA tools, to decrease
      APP mRNA levels. Additionally, we demonstrated that APP-ribozymes are effective
      at decreasing APP mRNA and protein levels as well as Abeta levels in neuronal
      cells. Our results could lay the groundwork for a new protective treatment for
      AD.

PMID- 22482080
TI  - A unifying hypothesis for familial and sporadic Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterised by the aggregation of two quite
      different proteins, namely, amyloid-beta (Abeta), which forms extracellular
      plaques, and tau, the main component of cytoplasmic neurofibrillary tangles. The
      amyloid hypothesis proposes that Abeta plaques precede tangle formation but there
      is still much controversy concerning the order of events and the linkage between
      Abeta and tau alterations is still unknown. Mathematical modelling has become an
      essential tool for generating and evaluating hypotheses involving complex
      systems. We have therefore used this approach to discover the most probable
      pathway linking Abeta and tau. The model supports a complex pathway linking Abeta
      and tau via GSK3beta, p53, and oxidative stress. Importantly, the pathway
      contains a cycle with multiple points of entry. It is this property of the
      pathway which enables the model to be consistent with both the amyloid hypothesis
      for familial AD and a more complex pathway for sporadic forms.

PMID- 22482081
TI  - Gastric composite tumor of alpha fetoprotein-producing carcinoma/hepatoid
      adenocarcinoma and endocrine carcinoma with reference to cellular phenotypes.
AB  - Alpha-fetoprotein-producing carcinoma (AFPC)/hepatoid adenocarcinoma (HAC) and
      neuroendocrine carcinoma (NEC) are uncommon in the stomach. Composite tumors
      consisting of these carcinomas and their histologic phenotypes are not well
      known. Between 2002 and 2007, to estimate the prevalence of composite tumors
      consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens
      obtained from 294 consecutive patients treated surgically for gastric cancer. We
      examined histological phenotype of tumors of AFPC or NEC containing the composite
      tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2,
      and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or
      mixed phenotype, and NEC frequently showed the gastric phenotype. In the
      composite tumor, the tubular and hepatoid components showed the gastric
      phenotype, and the neuroendocrine component showed the mixed type. The unique
      composite tumor predominantly showed the gastric phenotype, and the hepatoid and
      neuroendocrine components were considered to be differentiated from the tubular
      component.

PMID- 22482082
TI  - Immunoreactivity of the 14F7 Mab (Raised against N-Glycolyl GM3 Ganglioside) as a
      Positive Prognostic Factor in Non-Small-Cell Lung Cancer.
AB  - Lung carcinoma is the leading cause of cancer-related mortality worldwide.
      Therefore, numerous studies are focusing on the assessment of other biological
      and molecular prognostic factors in these tumors. We evaluated the relationship
      between 14F7 Mab reactivity, pathological features, DNA-content and S-phase
      fraction (SPF), and their impact in the survival of NSCLC patients. Hematoxylin
      and eosin staining and immunohistochemistry optical microscopy assays as well as
      DNA content and SPF measuring using flow cytometry were performed. The 14F7
      reactivity was widely observed in NSCLC sections, no depending of the
      clinicopathological characteristics. We also obtained differences in the
      intensity of reaction with 14F7 as well as in the SPF between diploid and
      aneuploid carcinomas. Patients with diploid tumors showing higher SPF and 14F7
      reaction joint to a low mitotic index displayed higher survival rates. Our
      results are in agreement with the assumption of the possible positive prognostic
      value of 14F7 staining in NSCLC.

PMID- 22482084
TI  - Expression of CD44v6 and Its Association with Prognosis in Epithelial Ovarian
      Carcinomas.
AB  - The aim of this study was to evaluate CD44v6 protein expression and its
      prognostic value of CD44v6 in ovarian carcinoma. The expression of CD44v6 was
      analyzed in 62 patients with ovarian carcinoma by immunohistochemical method. The
      data obtained were analyzed by univariate and multivariate analyses. The present
      study clearly demonstrates that tumor tissues from 41 (66.1%) patients showed
      positive expression with CD44v6. The expression of CD44v6 was significantly
      correlated with histological type, FIGO stage and histological grade of ovarian
      carcinomas. Concerning the prognosis, the survival period of patients with CD44v6
      positive was shorter than that of patients with CD44v6 negative (36.6% versus
      66.7%, 5-year survival, P < 0.05). Univariate analysis showed that CD44v6
      expression, histological type, FIGO stage and histological grade were associated
      with 5-year survival, and CD44v6 expression was associated with histological
      type, FIGO stage and histological grade and 5-year survival. In multivariate
      analysis, using the COX-regression model, CD44v6 expression was important
      prognostic factor. In conclusion, these results suggest that CD44v6 may be
      related to histological type, FIGO stage and histological grade of ovarian
      carcinomas, and CD44v6 may be an important molecular marker for poor prognosis in
      ovarian carcinomas.

PMID- 22482083
TI  - Animal Models in Behcet's Disease.
AB  - Behcet's disease is a chronic, recurrent, multisystemic, inflammatory disorder
      affecting mainly the oral and urogenital mucosa and the uveal tract. Although the
      etiology and pathogenesis of Behcet's disease are unknown, numerous etiologies
      have been proposed, including environmental, infectious, and immunological
      factors; an autoimmune basis, characterized by circulating immune complexes and
      complement activation, has gained increasing acceptance. To test and understand
      immunopathogenesis of Behcet's disease, animal models were developed based on
      enviromental pollutants, bacterial and human heat shock protein derived peptides,
      and virus injections. Using these animal models separately and/or concurrently
      allows for a more effective investigation into Behcet's disease. Animal models
      developed in the last 10 years aim at the development of efficient and safe
      treatment options.

PMID- 22482085
TI  - The Effect of Cold Ischemia Time and/or Formalin Fixation on Estrogen Receptor,
      Progesterone Receptor, and Human Epidermal Growth Factor Receptor-2 Results in
      Breast Carcinoma.
AB  - Aims. To compare the results of estrogen and progesterone receptors (ER, PR), and
      human epidermal growth factor receptor-2 (HER2) expression status on biopsy and
      excision specimens and to evaluate the effect of cold ischemia time and/or
      formalin fixation on these biomarkers. Methods. Breast carcinomas that were
      diagnosed between 2007 and 2009 by core needle biopsy, and subsequently excised
      in our institution, were included in the study. Data regarding the tumor
      morphology, grade, and ER, PR, and HER2 status were retrospectively collected
      from the pathology reports. Results. Five out of 149 (3.4%) cases with ER
      positive receptor status in the biopsy specimen became ER-negative in the
      subsequent excision specimen. Nine out of 126 (7.1%) cases with PR-positive
      receptor status in the biopsy specimen became PR-negative in the excision
      specimen. Receptor status change was predominantly seen in tumors with low ER and
      PR receptor expression. HER2 results were consistent between biopsy and excision
      specimens in all cases tested. Conclusions. Cold ischemia time and/or formalin
      fixation affect mainly ER and PR testing with low Allred scores and support the
      implementation of the ASCO/CAP guidelines. HER2 results, however, were not
      affected in our limited number of patients.

PMID- 22474619
TI  - Current Pharmacological Management in Juvenile Huntington's Disease.
AB  - BACKGROUND: The clinical presentation of Juvenile Huntington's Disease (JHD) can
      be very different from adult-onset HD with little evidence to guide symptomatic
      management. AIM: To survey the current use of pharmacological treatments for JHD.
      METHODS: Patients were identified through the HD Association, Hospital Doctors
      and the European Huntington's Disease Network REGISTRY study. RESULTS: The most
      commonly prescribed agents were anti-psychotics (24/45), anti-depressants (17/45)
      and anti-parkinsonian medications (15/45). 5 patients were taking more than 8
      medications. CONCLUSIONS: The most commonly prescribed group of medication was
      the anti-psychotic. Many patients were on multiple therapies, highlighting the
      need to rationalise medications.

PMID- 22482088
TI  - Better and better: Adopting advances in shoulder surgery.

PMID- 22474619
TI  - Current Pharmacological Management in Juvenile Huntington's Disease.
AB  - BACKGROUND: The clinical presentation of Juvenile Huntington's Disease (JHD) can
      be very different from adult-onset HD with little evidence to guide symptomatic
      management. AIM: To survey the current use of pharmacological treatments for JHD.
      METHODS: Patients were identified through the HD Association, Hospital Doctors
      and the European Huntington's Disease Network REGISTRY study. RESULTS: The most
      commonly prescribed agents were anti-psychotics (24/45), anti-depressants (17/45)
      and anti-parkinsonian medications (15/45). 5 patients were taking more than 8
      medications. CONCLUSIONS: The most commonly prescribed group of medication was
      the anti-psychotic. Many patients were on multiple therapies, highlighting the
      need to rationalise medications.

PMID- 22482089
TI  - An analysis of the shoulder and elbow section of the orthopedic in-training
      examination.
AB  - The Orthopaedic In-Training Examination (OITE) has been administered to
      orthopedic residents to assess knowledge and measure teaching quality. We
      performed a detailed analysis of the shoulder and elbow (S&E) section of the OITE
      relating to question content, recommended American Academy of Orthopaedic
      Surgeons references, and resident performance. S&E questions from the 2005-2009
      examinations were analyzed for resident performance scores, tested topics, tested
      imaging modalities, tested treatment modalities, taxonomy classification, and
      recommended references. The S&E section made up 5.9% of the OITE. Mean resident
      performance on the entire OITE and on the S&E section improved during each
      training year. Imaging modality questions typically involved radiographs,
      magnetic resonance imaging, and computed tomography. These questions made up
      37.5% of the S&E section. Treatment modality questions made up 45% of the S&E
      section and related mostly to shoulder arthroplasty and rehabilitation. Taxonomy
      classification showed that recall questions were most common. However, mean
      resident performance was minimally affected by question type. Recommended
      references were most commonly journal articles. Results of this study provided
      unique information related to content, recommended references, and resident
      performance on the S&E section of the OITE. We hope that use of this information
      will help improve resident performance and optimize S&E curricula.

PMID- 22482090
TI  - Incidence and costs of defensive medicine among orthopedic surgeons in the United
      States: a national survey study.
AB  - Defensive medicine is defined as medical practices that may exonerate physicians
      from liability without significant benefit to patients. No study has evaluated
      the United States national incidence of defensive medicine in the field of
      orthopedic surgery. In the study reported here, we investigated the practice of
      defensive medicine and the resultant financial implications of such behavior by
      orthopedic surgeons in the US. A Web-based survey was sent to 2000 orthopedic
      surgeons in the US. Of the 1214 respondents, 1168 (96%) reported having practiced
      defensive medicine by ordering imaging, laboratory tests, specialist referrals,
      or hospital admissions mainly to avoid possible malpractice liability. On
      average, 24% of all ordered tests were for defensive reasons. Mean national
      Medicare payment information was used to calculate the cost of defensive medicine
      per respondent: approximately $100,000 per year. With there being 20,400
      practicing orthopedic surgeons in the US, we estimated that the national cost of
      defensive medicine for the specialty of orthopedic surgery is $2 billion
      annually. Orthopedic surgeons' defensive medicine is a significant factor in
      health care costs and is of marginal benefit to patients. Policies aimed at
      managing liability risk may be useful in containing such practices.

PMID- 22482091
TI  - Accuracy of the acetabular index using the percutaneous assisted total hip
      technique.
AB  - In minimally invasive total hip arthroplasty (THA), proper acetabular component
      positioning can be difficult to achieve without navigational or intraoperative
      radiographic methods. Acetabular components placed in excessive abduction can
      lead to early failure and dislocation. This article describes a series of 74
      consecutive primary THAs (71 patients, 3 bilateral) performed using a
      percutaneous assisted THA technique that does not require navigation, yet allows
      adequate visualization for accurate acetabular cup placement. No patients were
      excluded (because of body mass index or abnormal anatomy) from the study. Mean
      abduction angle for all hips was 45 degrees . The goal was acetabular abduction
      angle between 35 degrees  and 55 degrees . This goal was achieved in 72 of the 74
      hips (97.3%). Proper acetabular abduction angle can be achieved in the majority
      of cases using this new soft-tissue sparing approach for THA.

PMID- 22482092
TI  - Ochronotic arthropathy: diagnosis and management: a critical review.
AB  - Alkaptonuria, a rare hereditary metabolic disorder, is characterized by
      accumulation of homogentisic acid in the connective tissues resulting from lack
      of the enzyme homogentisic acid oxidase. Ochronosis, dark pigmentation of
      connective tissues, is the musculoskeletal manifestation of alkaptonuria. In this
      article, we report the case of a 53-year-old man who had ochronotic arthropathy
      and advanced degenerative changes in the shoulders managed with bilateral total
      shoulder arthroplasty. Three-year follow-up results were satisfactory: good range
      of motion, no pain, and no signs of prosthesis loosening. Shoulder function was
      significantly improved after surgery, as documented by Constant scores. This case
      suggests that shoulder prosthesis results are not affected by alkaptonuria.

PMID- 22482093
TI  - Fulminant spread of a femur anaerobic osteomyelitis to abdomen in a 17-year-old
      boy.
AB  - To our knowledge, distant spread of infection in anaerobic osteomyelitis has not
      been described before. In this article, we report a case of anaerobic
      osteomyelitis of femur with fulminant spread of infection to the abdomen in a 17
      year-old boy with no predisposing medical factors and minimal bone involvement.

PMID- 22482094
TI  - Vascular inflammation and endothelial dysfunction in fracture healing.
AB  - Angiogenesis is an important step in bone fracture healing. In this article, we
      report on the healing of long bone fractures, and the involvement of the vascular
      and the inflammatory systems in the process. We conducted a prospective study of
      20 healthy adults with traumatic long bone fracture. One week after fracture, and
      then 1 month later, we evaluated markers of inflammation: vascular responsiveness
      (brachial endothelial function and ankle brachial index) and inflammatory and
      cytokine levels osteopontin [OPN], E-selectin, and vascular endothelial growth
      factor [VEGF]). Long bone fractures caused intense vascular and inflammatory
      responses, represented by high levels of OPN, Eselectin, and VEGF. In vivo
      measurements demonstrated severe endothelial dysfunction, which could support the
      idea that the vascular system is recruited to build new blood vessels that
      support bone regeneration.

PMID- 22482095
TI  - Bone grafting of humeral head cystic defects during rotator cuff repair.
AB  - Cystic bony defects of the humeral head greater tuberosity are often encountered
      during rotator cuff repair. These defects may be idiopathic, related to a
      patient's rotator cuff disease, or secondary to suture anchor placement from
      previous repairs. Some cysts are visible on preoperative magnetic resonance
      imaging, but most are discovered on footprint exploration or implant removal
      during revision surgery. These osseous defects reduce biological healing capacity
      and may decrease repair fixation strength. Bone grafting techniques are needed to
      address these defects. In this article, we present an arthroscopic allograft
      compaction technique with concomitant suture anchor rotator cuff repair.

PMID- 22482096
TI  - Does low-intensity pulsed ultrasound reduce time to fracture healing? A meta
      analysis.
AB  - We conducted a meta-analysis of randomized controlled trials to obtain a more
      precise estimate of the effect of low-intensity pulsed ultrasound (LIPU) versus
      placebo on the acceleration of fracture healing in skeletally mature persons and
      to determine if any serious adverse events are associated with LIPU when used to
      accelerate fracture healing.

PMID- 22482097
TI  - Using the 320-Multidetector Computed Tomography scanner for four-dimensional
      functional assessment of the elbow joint.
AB  - As described in this case report, the use of the 320-Multidetector Computed
      Tomography scanner (Aquilion One, Toshiba Medical Systems, Japan) to produce
      continuous 3-dimensional images in real time, over a distance of 16 cm in the z
      axis, proved to aid in the diagnosis of a patient's restrictive elbow joint. This
      state-of-the-art scanner allows fast and noninvasive dynamic-kinematic functional
      evaluation of the elbow joint in vivo. It will also be applicable to kinematic
      studies of other joints.

PMID- 22482098
TI  - Hemiepiphyseal stapling for ankle valgus in multiple hereditary exostoses.
AB  - If left uncorrected, valgus ankle deformity in multiple hereditary exostoses can
      cause significant disability in skeletally immature children and in adults.
      Various management methods have been described, including hemiepiphyseal
      stapling, transphyseal screw placement, fibular-Achilles tenodesis, distal tibial
      osteotomy, and ablative epiphyseodesis. In this article, we report the cases of 3
      skeletally immature children who had undergone hemiepiphyseal stapling of the
      medial distal tibial epiphysis for correction of valgus ankle deformity in
      multiple hereditary exostoses. Correction of the tibiotalar axis, in relation to
      chronological and bone age, was evaluated. Hemiepiphyseal stapling of the medial
      distal tibial epiphysis provides ipsilateral corrective potential while allowing
      staple removal for reversal of growth retardation. This procedure is useful in
      the management of ankle valgus in multiple hereditary exostoses.

PMID- 22482099
TI  - Updates in the management of orthopedic soft-tissue injuries associated with
      lower extremity trauma.
AB  - Management of traumatic soft-tissue injuries remains a challenging and ever
      evolving field within orthopedic surgery. The basic principle of addressing life
      before limb in the initial assessment of critically injured patients has not
      changed. Although arteriography remains the gold standard for vascular injury
      screening, computed tomography angiography is being used more often to determine
      limb viability, and its sensitivity and specificity for detecting vascular
      lesions are reported to be excellent. Thorough debridement and irrigation with
      early institution of antibiotics are crucial in preventing infection; debridement
      should be performed urgently once life-threatening conditions have been
      addressed. Increasing use of vacuum-assisted closure therapy has created a trend
      down the reconstructive ladder, with improvements in resulting wound closure.
      Although the orthoplastics approach and new microsurgical techniques have made
      limb salvage possible in even the most severely injured extremities, it is
      important to clearly identify the zone of injury and to inform patients and their
      families of the outcomes of limb salvage versus amputation. Results from the LEAP
      (Lower Extremity Assessment Project) trials and similar studies should guide
      orthopedic surgeons in the management of these complex injuries. Nevertheless, it
      is important to individualize management plans according to patient factors.

PMID- 22482100
TI  - Don't bet the ranch on ACOs.

PMID- 22482101
TI  - Help your patient "get" what you just said: a health literacy guide.

PMID- 22482102
TI  - Not just a sprain: 4 foot and ankle injuries you may be missing.

PMID- 22482103
TI  - Thyroid nodules: when is an aggressive evaluation warranted?

PMID- 22482104
TI  - How to recognize a patient who's high on "bath salts".

PMID- 22482105
TI  - What's best for IBS?

PMID- 22482106
TI  - Unsightly rash on shin. Necrobiosis lipoidica diabeticorum.

PMID- 22482107
TI  - Clinical inquiry. Do antibiotics shorten symptoms in patients with purulent nasal
      discharge?

PMID- 22482108
TI  - Torture survivors: what to ask, how to document.

PMID- 22482109
TI  - The benefits of interdisciplinary pain management.

PMID- 22482110
TI  - Pain--it's not that simple.

PMID- 22482111
TI  - Men, women, and migraine: the role of sex, hormones, obesity, and PTSD.

PMID- 22482112
TI  - The fragment molecular orbital and systematic molecular fragmentation methods
      applied to water clusters.
AB  - Two electronic structure methods, the fragment molecular orbital (FMO) and
      systematic molecular fragmentation (SMF) methods, that are based on fragmenting a
      large molecular system into smaller, more computationally tractable components
      (fragments), are presented and compared with fully ab initio results for the
      predicted binding energies of water clusters. It is demonstrated that, even when
      explicit three-body effects are included (especially necessary for water clusters
      due to their complex hydrogen-bonded networks) both methods present viable,
      computationally efficient alternatives to fully ab initio quantum chemistry.

PMID- 22482113
TI  - Unraveling the Fischer-Tropsch mechanism: a combined DFT and microkinetic
      investigation of C-C bond formation on Ru.
AB  - A combined modelling study on the Fischer-Tropsch Mechanism on Ru(0001). The DFT
      results presented herein approve the idea that the carbide mechanism is not the
      main reaction path in the synthesis of liquid hydrocarbons on Ru{0001}. The
      direct reaction of a CH(x)(s) species with a CO(s) species is kinetically and
      thermochemically preferred over CO dissociation and the hydrogenation of carbon
      monoxide can be seen as the initiation reaction of the hydrocarbon polymerisation
      process. Moreover, this study shows that CO dissociation is favoured over
      desorption on Ru{0001}, while on the analogue Co facet desorption is clearly
      favoured. This study therefore is an important further confirmation on new
      thinking in the Fischer-Tropsch synthesis. The fundamental insight gained in
      these studies will be of paramount importance for engineers optimising the FT
      process. Optimisation will not only lower the cost of FT fuels but simultaneously
      lower energy consumption and emissions. 

PMID- 22482114
TI  - Guanidinium in aqueous solution studied by quantum mechanical charge field
      molecular dynamics (QMCF-MD).
AB  - Structure and dynamics of guanidinium in aqueous solution were examined via a
      double zeta HF level Quantum Mechanical Charge Field-Molecular Dynamics (QMCF-MD)
      simulation, as well as two Molecular Mechanics-Molecular Dynamics (MM-MD)
      simulations, parametrised via the Amber99 parameter set, employing the side chain
      of arginine as a template. Coulombic parameters were fitted via Mulliken
      population data of the QM simulation, as well as via the recommended restrained
      electrostatic potential fit (RESP). Although guanidinium is one of the most
      weakly hydrated cations yet characterised, its hydration pattern is quite complex
      and pronounced in the quantum mechanical simulation. The positive charge is
      mainly located on the central carbon, resulting in strong solute-oxygen
      coordination. Hydrogen bonds are mainly donated by the amide hydrogens, but are
      also accepted via the nitrogens to a very low extent. Detailed analysis of
      structure and dynamics, comparing the applied QM and MM models, provides evidence
      that the arginine parametrisation leads to highly different results than the
      quantum mechanical treatment, and that the RESP parametrisation is too polarised.

PMID- 22482115
TI  - Van der Waals forces in the perfluorinated metal-organic framework zinc 1,2-bis(4
      pyridyl)ethane tetrafluoroterephthalate.
AB  - Traditional density functional theory (DFT) and dispersion-corrected DFT
      calculations are performed to investigate the metal-organic framework zinc 1,2
      bis(4-pyridyl)ethane tetrafluoroterephthalate (Znbpetpa). Without dispersion
      correction, straightening of the zigzag C-O-Zn chain connecting the secondary
      building units across the diagonal of the unit cell is observed, accompanied by a
      large anisotropic expansion of the structure along one cell parameter. The
      results show that van der Waals dispersion forces and specifically Zn-C
      equatorial interactions and the resulting effects on the zigzag chain play an
      important role in maintaining key structural features which match with
      experimental observations. It is suggested that the pore volume of the framework
      could be controlled by substituting the Zn metal centre with another transition
      element of different polarizability, while maintaining functional linkers. 

PMID- 22482116
TI  - Endothelium: from cellophane  to orchestral maestro.
AB  - Endothelial cells from human umbilical veins were first cultured nearly four
      decades ago, initiating explosive growth in research in vascular biology and
      leading to major insights into angiogenesis, vasculogenesis, and tumor biology.
      Recent studies now promise to open new horizons in regenerative medicine as well
      as organ engineering.

PMID- 22482117
TI  - Sensitivity of whole blood clotting time and activated partial thromboplastin
      time for factor IX: relevance to gene therapy and determination of post
      transfusion elimination time of canine factor IX in hemophilia B dogs.

PMID- 22482118
TI  - Definition of post-thrombotic syndrome following lower extremity deep venous
      thrombosis and standardization of outcome measurement in pediatric clinical
      investigations.

PMID- 22482119
TI  - Retraction. Sphingosine-1-phosphate receptor-2 deficiency leads to inhibition of
      macrophage proinflammatory activities and  atherosclerosis  in apoE-deficient
      mice.

PMID- 22482120
TI  - Festschrift in honor of Trevor Parmenter.

PMID- 22482122
TI  - Making progress against HIV/AIDS.

PMID- 22482123
TI  - Executive director of Global Fund steps down.

PMID- 22482121
TI  - Desire for pregnancy and risk behavior in young HIV-positive women.
AB  - This cross-sectional study utilized data from 130 young women with behaviorally
      acquired HIV to examine the association between desire for pregnancy (DFP) and
      both sociodemographic variables and sexual risk behaviors. A single item was
      utilized to assess DFP. Bivariate and multivariate regression analyses were
      conducted. At the bivariate level, DFP was associated with increased rates of
      intercourse, decreased condom use, increased partner concurrency, increased rates
      of unprotected sex with a nonconcordant partner, and a higher number of previous
      sexually transmitted infections (STIs). Multivariate analyses suggested that DFP
      was associated with increased likelihood of recent intercourse, condom
      unprotected sex, and oral sex. DFP was related to few sociodemographic variables
      but was associated with having fewer children currently, a history of
      victimization, and decreased rates of disclosure of HIV status. The few
      sociodemographic variables that were associated with DFP suggest that social
      relationships may play a role in DFP. DFP was associated with sexual behaviors
      that may place young women at risk for STI acquisition and secondary HIV
      transmission to partners. Health care providers should assess DFP in routine HIV
      care, providing education about fertility options, interventions for vertical
      transmission, family planning, and risk reduction counseling.

PMID- 22482124
TI  - Protein phosphatases and their regulation in the control of mitosis.
AB  - Cell cycle transitions depend on protein phosphorylation and dephosphorylation.
      The discovery of cyclin-dependent kinases (CDKs) and their mode of activation by
      their cyclin partners explained many important aspects of cell cycle control. As
      the cell cycle is basically a series of recurrences of a defined set of events,
      protein phosphatases must obviously be as important as kinases. However, our
      knowledge about phosphatases lags well behind that of kinases. We still do not
      know which phosphatase(s) is/are truly responsible for dephosphorylating CDK
      substrates, and we know very little about whether and how protein phosphatases
      are regulated. Here, we summarize our present understanding of the phosphatases
      that are important in the control of the cell cycle and pose the questions that
      need to be answered as regards the regulation of protein phosphatases.

PMID- 22482126
TI  - Conceptual models for carbonate aquifers. 1969.

PMID- 22482127
TI  - Aleukemic variant of mast cell leukemia.

PMID- 22482128
TI  - Intracranial haemorrhage with a twist.

PMID- 22482129
TI  - Atypical atlanto-axial subluxation.

PMID- 22482130
TI  - Modality mix and the cost of dialysis.

PMID- 22482125
TI  - Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus.
AB  - Inhibition of proliferation by cell-to-cell contact is essential for tissue
      organization, and its disruption contributes to tumorigenesis. The FERM domain
      protein Merlin, encoded by the NF2 tumour suppressor gene, is an important
      mediator of contact inhibition. Merlin was thought to inhibit mitogenic
      signalling and activate the Hippo pathway by interacting with diverse target
      effectors at or near the plasma membrane. However, recent studies highlight that
      Merlin pleiotropically affects signalling by migrating into the nucleus and
      inducing a growth-suppressive programme of gene expression through its direct
      inhibition of the CRL4DCAF1 E3 ubiquitin ligase. In addition, Merlin promotes the
      establishment of epithelial adhesion and polarity by recruiting Par3 and aPKC to
      E-cadherin-dependent junctions, and by ensuring the assembly of tight junctions.
      These recent advances suggest that Merlin acts at the cell cortex and in the
      nucleus in a similar, albeit antithetic, manner to the oncogene beta-catenin.

PMID- 22482131
TI  - Burkitt lymphoma: the role of Epstein-Barr virus revisited.

PMID- 22482132
TI  - Exorcising the specter of nighttime hypoglycemia.

PMID- 22482133
TI  - Genetic and nongenetic determinants of MTX efficacy in RA.

PMID- 22482134
TI  - MTHFR polymorphisms and MTX toxicity in RA.

PMID- 22482135
TI  - Meta-analysis of MTHFR polymorphisms and MTX response in RA.

PMID- 22482136
TI  - A pilot study for using fecal immunochemical testing to increase colorectal
      cancer screening in Appalachia, 2008-2009.
AB  - INTRODUCTION: The Appalachian region of the United States has disproportionately
      high colorectal cancer (CRC) death rates and low screening rates. The purpose of
      this pilot study was to assess acceptability of a take-home fecal immunochemical
      test (FIT) and the effect of follow-up telephone counseling for increasing CRC
      screening in rural Appalachia. METHODS: We used a prospective, single-group,
      multiple-site design, with centralized laboratory reports of screening adherence
      and baseline and 3-month questionnaires. Successive patients, aged 50 or older,
      at average CRC risk and due for screening were enrolled during a routine visit to
      3 primary care practices in rural Appalachian Pennsylvania and received a free
      take-home FIT and educational brochure. Those who had not returned the test 2
      weeks later were referred for telephone counseling. RESULTS: Of 232 patients
      approached, 200 (86.2%) agreed to participate. Of these, 145 (72.5%) completed
      the FIT as recommended (adherent) and 55 (27.5%) were referred for telephone
      counseling (nonadherent), of whom 23 (41.8%) became adherent after 1 to 2
      counseling sessions, an 11.5 percentage-point increase in screening after
      telephone counseling and 84% FIT adherence overall. Lack of CRC-related knowledge
      and perceived CRC risk were the screening barriers most highly associated with
      nonadherence. Although not statistically significant, the rate of conversion to
      screening adherence was higher among participants who received telephone
      counseling compared to an answering machine reminder. CONCLUSION: If confirmed in
      future randomized trials, provider-recommended take-home FIT and follow-up
      telephone counseling may be methods to increase CRC screening in Appalachia.

PMID- 22482137
TI  - Weight status of American Indian and white elementary school students living in
      the same rural environment, Oklahoma, 2005-2009.
AB  - INTRODUCTION: Studies have assessed rates of childhood obesity in diverse
      populations, but few have been able to compare the weight status of American
      Indian and white children living in the same community and attending the same
      schools. The objective of this study was to measure and compare the weight status
      of American Indian and white elementary school students (kindergarten through 5th
      grade) from 2005 through 2009 in an Oklahoma school district. METHODS: We
      assessed height, weight, age, and sex to calculate body mass index, body mass
      percentile, and categorical weight status of students, based on the Centers for
      Disease Control and Prevention 2000 Growth Charts. We used binomial regression to
      generate risk ratios (RRs) to compare student weight status by race, sex, and
      age. RESULTS: An average of 753 students was measured in each year; mean age was
      8.3 years. From 2005 through 2009, 45.4% of American Indian students and 65.1% of
      white students were healthy weight or underweight. Greater proportions of
      American Indian children were very obese (weighted average RR, 2.0); obese
      (weighted average RR, 1.6), or overweight (weighted average RR, 1.8) compared
      with white children. The overall prevalence of excess weight changed little
      during the study period. CONCLUSION: American Indian children had a greater risk
      of being overweight, obese, or very obese than white children from the same rural
      environment.

PMID- 22482139
TI  - Loan repayment program  promotes food animal practice.

PMID- 22482138
TI  - A community-driven approach to identifying "winnable" policies using the Centers
      for Disease Control and Prevention's Common Community Measures for Obesity
      Prevention.
AB  - Federally funded, community-based participatory research initiatives encourage
      the development and implementation of obesity prevention policies. In 2009, the
      Centers for Disease Control and Prevention (CDC) published the Common Community
      Measures for Obesity Prevention (COCOMO), which include recommended strategies
      and measures to guide communities in identifying and evaluating environmental and
      policy strategies to prevent obesity. Agreeing on "winnable" policy issues can be
      challenging for community members. We used CDC's COCOMO to structure in-depth
      interviews and group discussions with local stakeholders (ie, planners, town
      managers, and a local community advisory council) to stimulate interest in and
      identify health-promoting policies for local policy and planning agendas. We
      first asked stakeholders to rank the COCOMO recommendations according to
      feasibility and likelihood of success given community culture, infrastructure,
      extent of leadership support, and likely funding support. Rankings were used to
      identify the most and least "winnable" COCOMO policy strategies. We then used
      questions from the evidence-based Community Readiness Handbook to aid discussion
      with stakeholders on the facilitators and barriers to enacting the most and least
      winnable policy options identified. Finally, we discuss potential adaptations to
      COCOMO for rural jurisdictions.

PMID- 22482140
TI  - Speakers discuss  complexities  of heartworm disease.

PMID- 22482141
TI  - [Is it necessary to introduce the concept of craving into clinical practise?].

PMID- 22482143
TI  - Panel offers forum  on PetMed Express.

PMID- 22482142
TI  - Sessions address common behavioral problems.

PMID- 22482144
TI  - Congress considers  US egg production standards.

PMID- 22482145
TI  - Supreme Court strikes down Calif. slaughter rules.

PMID- 22482146
TI  - Network created  to improve food, drug  investigations.

PMID- 22482147
TI  - Ovariectomy versus  ovariohysterectomy.

PMID- 22482148
TI  - Veterinary education:  challenges and opportunities.

PMID- 22482149
TI  - Thoughts on sentimental  value of animals.

PMID- 22482150
TI  - Cardiac pacing and arrhythmia management.

PMID- 22482151
TI  - Autologous chondrocyte implantation.

PMID- 22482152
TI  - Vascular surgery.

PMID- 22482153
TI  - [Why is the incidence of post-vaccination interstitial pneumonia high in Japan?].

PMID- 22482154
TI  - [Indications for vaginal delivery with forceps application].
AB  - The aim of the study was to establish indications for operative vaginal delivery
      by extraction of the fetus with forceps in modern obstetrics. MATERIAL AND
      METHODS: This is a retro- and prospective study which includes 672 forceps
      deliveries in the period of 1994-2008 in Maternity hospital Sofia. Simpson and
      Kielland were used for extractions subject to appropriate indications and
      conditions, regardless of the gestational week of pregnancy. RESULTS: The most
      frequent indication for forceps application is fetal asphyxia (78.1%) and
      considering the frequency for 15 years it is the permanent, leading indication
      for forceps in modern obstetrics. Arrest of the head in the same plane of the
      pelvis was the indication in 23.6% of the cases it varies and is rarely primary
      through the 15 year period. Ineffective uterine contractions and/or pushes
      (16.7%) tends to decrease its frequency. Avoiding maternal efforts in the second
      stage of labor (8.5%) and in 50% of the cases was indicated for women with
      cardiovascular diseases. Malpositions (7.7%) increases through the years probably
      secondary to epidural analgesia. Indication preeclampsia-eclampsia is described
      in 1.3% of cases, followed by genital bleeding by 1.9% and prolapse of the
      umbilical cord by 0.6% and they are more incidentally reasons for application of
      forceps. CONCLUSION: Asphyxia of the fetus is the most common and a leading
      indication for extraction of the fetus with forceps. Ineffective uterine
      contractions and the arrest of the head in the same plane of the pelvis are
      consistent in their occurrence and lead to prolonged labor. In certain critical
      conditions (genital bleeding, prolapse of the umbilical cord and eclampsia)
      extraction of the fetus with forceps remains the only way for fast vaginal
      delivery.

PMID- 22482155
TI  - [Short term outcome after active obstetric management of very low birthweight
      infants].
AB  - Increased survival in infants weighing less than 1500g (VLBW) in recent decades
      is largely due to active perinatal management and intensive neonatal care. AIMS:
      To analyze the relationship between antenatal corticosteroid (ACS)
      administration, mode of delivery and the short term outcome in VLBW infants.
      METHODS: A total of 563 neonates weighing < 1500 g was studied between 01.01.2008
      and 30.06.2010, distributed according the outcome into 3 groups: 330 healthy, 150
      with chronic morbidities (bronchopulmonary dysplasia - supplemental O2 at 28
      days, intraventricular hemorrhage gr.Ill-IV or cystic periventricular
      leucomalacia, retinopathy of prematurity gr.llI-V), 83 died. Mode of delivery,
      ACS and their influence on the outcome were evaluated by multinomial logistic
      regression analysis and the relative risk was calculated for each of them (OR).
      The ACS course was taken for completed if applicated in the 7 days before
      delivery. RESULTS: Lack of ACS significantly increased the risk of severe
      morbidities or death compared to the complete course: OR 2.6 and 4.9 respectively
      (p < 0.001). A higher risk was found comparing incomplete to complete course too:
      morbidities OR 2,3 (p = 0.01), death OR 3,1 (p = 0.01). Incomplete ACS did not
      improved outcome significantly. Mode of delivery didn't affected significantly
      the risk of morbidities. The relative risk of death was lower in neonates
      delivered by cesarean section compared with vaginal breech delivery (OR 0.2, p =
      0.005) but higher compared with vaginal vertex delivery (OR 2.1, p = 0,004). In
      this study we didn't analyze the indications for cesarean section, some of which
      were due to fetal distress and could influence the outcome. CONCLUSION: The
      active obstetric management for VLBW infants reduces the risk of death and
      survival with morbidities. The main protective factor is the complete ACS course.

PMID- 22482156
TI  - [Group B streptococcus (GBS) infection in newborns in university hospital
      "Maichin Dom" EAD Sofia for the period 2008-2010].
AB  - For the period 2008-2010 in the University Hospital "Maichin Dom" EAD were born
      10 774 babies. The newborns in the intensive care clinic (according to Apgar 1-5
      min, the severity of RDS, the birth weight, gestational age, C-reactive protein
      and the values of blood tests) were screened for mother-fetal infections
      immediately after birth. The tests performed were blood culture, stomach
      aspirate, ear, anal and nose secretion, throat and tracheal aspiration (if
      intubation was performed). In case of meningitis liquor was tested. Standard
      therapy included Ampicillin/Sulbactam. The healthy, eutrophic children were also
      screened for bacterial mother-fetal infections--routinely ear and stomach
      aspiration. The babies, without clinical and paraclinical symptoms, but positive
      for GBS colonization, were also treated with Ampicilin. As a result from the
      screening and therapy no cases with meningitis were detected, as well as late
      neonatal sepsis caused by GBS.

PMID- 22482157
TI  - [Laterally extended parametrectomy in cases with cervical carcinoma].
AB  - INTRODUCTION: Clinical staging of cervical carcinoma is not always an easy task,
      especially in cases with parametrial involvement, stage IIB. Therapeutic approach
      may differ in such patients- conservative (radio-, chemoradiation) therapy versus
      operative treatment. Research shows that the limits of the typical class III-IV
      radical hysterectomy may prove to be inadequate in relation to the dissection of
      the lateral parametria. A new surgical technique called laterally extended
      parametrectomy was published in 1993 and provides the means of total removal of
      the connective and lymphatic tissue up to the level of the true pelvic sidewall.
      MATERIAL AND METHODS: A retro- and prospective study was performed during the
      period between Jan 2008 and Feb 2011. A total of 17 radical hysterectomies with
      unilateral LEP were enrolled. Median age of patients was 51 years. Mean duration
      of surgery is 3 hours 57 min. Laterally extended parametrectomy was initiated in
      cases with clinically predetermined stage IB to II/IA cervical cancer. 3 patients
      were diagnosed with adenosquamous type of carcinoma, while the other 14 were with
      squamous cell cervical cancer. RESULTS: Positive iliac lymph nodes were found
      bilaterally in 7 patients, unilaterally also in 7 patients, while 3 cases proved
      to be negative. Paraaortic lymph node dissection was performed in 6 surgeries,
      with positive histology in 4 cases. Parametrial infiltration was found in 6
      patients, 3 of them bilateral. 8 of the patients had unilateral hydroureter.
      CONCLUSION: Laterally extended parametrectomy is a surgical technique which
      provides the means for full removal of the lymphatics and connective tissue up to
      the pelvic sidewall, during radical hysterectomy in patients with cervical
      cancer, stage IB and IIA, with positive iliac lymph nodes, as well as in stage
      IIB cases. It offers an efficient alternative for surgical treatment of locally
      advanced cervical cancer, opposed to the other therapeutic approaches.

PMID- 22482158
TI  - [Pregnancy and oncological diseases].
AB  - AIM: The oncological diseases during pregnancy are very rare, but the incidence
      rate is constantly increasing. The diagnosis and treatment of the cancer during
      pregnancy are connected with the risk of the diagnostic procedures on the foetus
      and the risk of the treatment methods upon the developing foetus. That is why we
      decided to assess and research our and foreign experience in this field. MATERIAL
      AND METHODS: We performed a retrospective research work in this field. For 10
      years period we examined: - 20 patients with precancer and cancer of the vulva
      combined with pregnancy - 70 patients with cervical cancer and pregnancy - 30
      patients with ovarian cancer and pregnancy - 60 patients with breast cancer and
      pregnancy The most important point in the diagnosis and treatment of the
      oncological diseases connected with pregnancy is not to delay the treatment of
      the pregnant woman. RESULTS: The patients with early stages of the cervical
      cancer connected with pregnancy are treated conservatively. The patients with
      invasive cervical cancer and pregnancy-the gestational age and the wish of the
      patient to have a baby are the main factors formulating the kind of treatment. In
      early I-st and II-nd trimester the patients with IB and IIA stage are treated
      with radical hysterectomy together with the foetus or the standard chemo
      radiotherapy. Advanced cervical cancer-IB2-II stage. In these patients pelvic
      radiotherapy with chemotherapy is used if the cancer is diagnosed in the first 20
      gestational weeks. Acording to us and the most foreign authors the adnexal masses
      must be eradicated surgically in the II-nd trimester of the pregnancy (13-16
      gestational weeks). The most ovarian cancers are in early stage and chemotherapy
      may be delayed after the delivery especially for epithelial tumors I-st stage.
      DISCUSSION: In precancer and cancer of the uterine cervix as well as in all other
      oncogynaecological and oncological diseases combined with pregnancy we offer 2
      algorithms to be used. CONCLUSION: The oncolgical types of treatment including
      surgery,chemotherapy and radiotherapy(with exception of radiotherapy for small
      pelvis and abdominal cavity) may safely be applied after the I-st trimester of
      the pregnancy.

PMID- 22482159
TI  - [Cerebral palsy--perinatal aspects].
AB  - Cerebral palsy is a group of non-progressive but often changing motor impairment
      syndromes resulting from lesions or anomalies occurring in the early stages of
      fetal development and childhood. This condition is responsible for significant
      emotional, financial and social difficulties for the patient and the family, and
      professionals providing specific care for these people. This review describes the
      incidence, risk factors and the etiopathogenesis of this condition. A lot of
      evidences of the relations between intrauterine infection, prematurity,
      prenosenost, intrapartalna asphyxia, multiple pregnancy and assisted reproductive
      techniques are decribed. In the review is has been demonstrated the most
      important aspects of perinatal cerebral palsy.

PMID- 22482160
TI  - [Pregnancy and trauma].
AB  - Anatomic and physiologic changes in pregnancy can mask or mimic injury, making
      diagnosis of trauma-related problems difficult. Care of pregnant trauma patients
      with severe injuries often requires a multidisciplinary approach involving an
      emergency clinician, trauma surgeon, obstetrician, anesthesiologist and
      neonatologist. The pregnant trauma patient presents a unique challenge because
      care must be provided for two patients--the mother and the fetus.

PMID- 22482161
TI  - [Polar bodies--by-product of oogenesis or source of information in assisted
      reproduction].

PMID- 22482162
TI  - [Hyperimmunoglobulin E syndrome (Job's syndrome)].
AB  - Job's syndrome (Hyperimmunoglobulin E syndrome) is a rare congenital immune
      deficiency condition, manifested by local and system changes. A case of
      successful pregnancy in patient, suffering from this rare disease is presented.
      The possible complications during the course of pregnancy, delivery and puerperal
      period and therapeutic alternatives during pregnancy are discussed.

PMID- 22482164
TI  - Using innovation to make care a priority.

PMID- 22482165
TI  - Transparency project will enable nurses to compare performance.

PMID- 22482163
TI  - [Pregnancy and delivery in patients with surgically corrected congenital extrophy
      of the bladder, through the operations of the continent urinary derivation].
AB  - Authors present two cases of pregnancy and delivery of patients with bladder
      extrophy. Both had undergone various and different reconstructive surgical
      operations in childhood, which gave them the opportunity to lead a normal life,
      to become pregnant and deliver. A total of three deliveries are observed--one
      with Caesarian, one--normal vaginal delivery and one--normal delivery with breech
      presentation. Bladder extrophy is a rare and severe innate anomaly of the genital
      urinary tract, associated with genital, urologic and orthopedic malformations.
      The main complications during pregnancy are infections and calculosis of the
      urinary tract, prematurity, malpresentations, genital prolapse. Premeditated
      Caesarian section is the method of delivery in almost every case with bladder
      extrophy, while normal vaginal delivery remains casuistic.

PMID- 22482166
TI  - No extra pay for staff who work on Queen's diamond jubilee holiday.

PMID- 22482167
TI  - Trust brings back badges in bid to celebrate nursing excellence.

PMID- 22482168
TI  - Mentors need more support to fail poorly performing students.

PMID- 22482169
TI  - Can health professionals stop the NHS reforms before it is too late?

PMID- 22482170
TI  - 'We cannot see how the NHS can survive without reform'.

PMID- 22482171
TI  - The new voice of public health nursing at the heart of Whitehall.

PMID- 22482172
TI  - All eyes on the patient.
AB  - As part of the Care campaign, nurse leaders and patients' representatives drew up
      ten 'priorities for action' that should be implemented by all healthcare
      providers. Top of the list is to ensure that every organisation makes patient
      care its core focus. This article looks at how some hospitals are already seeking
      to achieve this objective and what is being done to make patient care the top
      priority everywhere.

PMID- 22482173
TI  - Recovering from wave of destruction.
AB  - A year on from the tsunami that devastated the north east coastline of Japan,
      nurses are supporting people who lost loved ones, homes and businesses. Nurses
      and midwives are also caring for those affected by the meltdowns at the Fukushima
      nuclear power plant. Experts say the psychological toll of Fukushima is likely to
      be more significant than the relatively minor physical effects of radiation.

PMID- 22482174
TI  - The role of the clinical research nurse.
AB  - With increased emphasis on clinical research within the NHS, it is vital that
      training and educational opportunities are available to enable clinical research
      nurses to progress in their careers. This article describes the work of the
      clinical research nurse and examines the advantages and disadvantages of the
      role. It discusses the history of clinical research nursing and those aspects and
      guidelines that have shaped the way the role has developed. The lack of a career
      pathway for nurses who decide to pursue a career in nursing research and/or
      medical research is considered, and suggestions are made regarding the future of
      clinical research nursing and education.

PMID- 22482175
TI  - End of life care for patients following acute stroke.
AB  - End of life care is an important aspect of acute stroke nursing because stroke
      mortality rates remain high, despite advances in care. There is a national drive
      to improve the quality of end of life care in all clinical areas, including for
      stroke patients. Patients who have had a stroke should not be excluded from acute
      stroke care at the end of life. Stroke care should incorporate multidisciplinary
      working, anticipatory care planning and prescribing, and effective communication
      with patients and families. The use of end of life care pathways is widely
      recommended as best practice. Palliative care specialists may provide support
      where patients' needs are complex, while decisions to withhold cardiopulmonary
      resuscitation should be avoided immediately following stroke. Spiritual care
      extends beyond religious care and is the responsibility of the multidisciplinary
      team. Although more research is required about stroke care at the end of life,
      providing high-quality, patient-centred services for patients who have had a
      stroke and their families during this time is achievable.

PMID- 22482176
TI  - Management of patients with metastatic prostate cancer.
AB  - Prostate cancer is the most common cancer in men and is recognised as a
      significant health problem. Treatment of advanced or metastatic prostate cancer
      is challenging, and support and care should be tailored to meet the individual's
      needs. This article focuses on the pharmacological management of metastatic
      prostate cancer and the nurse's role in providing patients with information about
      the disease. It is hoped that this article will be used as a resource to improve
      patient care.

PMID- 22482177
TI  - Infection control.

PMID- 22482178
TI  - The value of expertise.

PMID- 22482180
TI  - Aim to please and you will.

PMID- 22482179
TI  - Offer an expert opinion.

PMID- 22482181
TI  - New delegation standards could strengthen nurses' accountability.

PMID- 22482182
TI  - Support workers face disciplinary action if they breach trust's code.

PMID- 22482183
TI  - Ministers offer cash incentives for same-day emergency care.

PMID- 22482184
TI  - Constant reform and privatisation distract nurses from core work.

PMID- 22482185
TI  - Nutritional benefits.
AB  - In the final article in our four-part series examining four strands of
      fundamental care, we examine why failure support adequate nutrition is a common
      complaint against hospital staff. We also look at the causes for these failures,
      and the variety of imaginative strategies many are using to tackle the problem.

PMID- 22482186
TI  - Listening and learning to make care better.
AB  - For the past two years the Patients Association has been recruiting volunteers to
      interview NHS patients about their care and negotiate solutions to problems
      raised. The pilot scheme has resulted in 16 projects to improve care in South
      West England. The 'patient ambassador' scheme is being extended to primary care
      and mental health trusts in the region.

PMID- 22482187
TI  - An overview of the effects of sickle cell disease in adolescents.
AB  - Specific complications of sickle cell disease (SCD) may emerge during
      adolescence, and education of patients and families is vital during transition
      from paediatric to adult health care. Adolescents with SCD have to adjust to the
      constraints of living with a lifelong chronic condition, and compliance with self
      care and medical treatments can be problematic. This article explores potential
      opportunities for intervention, and examines how the role of the adolescent
      clinical nurse specialist is pivotal in supporting patients and families during
      this transition.

PMID- 22482188
TI  - Understanding the role of non-technical skills in patient safety.
AB  - It is estimated that one in 300 patients admitted to hospital will die or be
      seriously injured as a result of medical errors (Chief Medical Officer 2009),
      many of which will be caused by human factors. This article examines a case study
      in which team error led to the death of a patient. It discusses some of the
      contributing human factors that were involved and explores possible ways to
      improve patient safety through education in human factors and non-technical
      skills.

PMID- 22482189
TI  - Meningococcal B disease: assessment and management.
AB  - Serogroup B meningococcal disease is the last main cause of bacterial meningitis
      and septicaemia in the UK. There is currently no vaccine against this serogroup.
      This article outlines the nature of meningococcal disease and highlights recent
      guidance from the National Institute for Health and Clinical Excellence on
      recognising and managing the disease in primary and secondary care. An update on
      progress towards a preventive vaccine is also discussed.

PMID- 22482190
TI  - Atrial fibrillation.

PMID- 22482191
TI  - A safer path on the net.

PMID- 22482192
TI  - Opportunity awaits abroad.

PMID- 22482193
TI  - Straight from the source.

PMID- 22482194
TI  - Infective endocarditis.
AB  - Despite the progress in medicine, infectious endocarditis is often diagnosed
      late, as its symptomatology is subject to a high variability. The clinical
      features are usually atypical. Since the introduction of the Duke criteria,
      clinical, bacteriological and echocardiographical findings are being integrated,
      allowing an earlier definitive diagnosis. The incidence remains practically
      stable. The decrease in post-rheumatic valvular heart disease at population level
      is compensated by an increase in degenerative valvular heart disease as
      predisposing factor. Moreover, the share of patients with intravascular foreign
      material is increasing. Endocarditis is usually characterized by a complicated
      development. About half of the patients develop heart failure as a consequence of
      the destruction of the affected valve with serious valvular insufficiency. One
      third of the patients present cerebral or peripheral embolization. Embolization
      predominantly occurs at the beginning, until the first two weeks of antibiotic
      treatment. Abscess formation occurs more frequently than is suspected based on
      echographical examinations. Particularly a Staphylococcus aureus infection in the
      presence of an artificial valve leads to extravalvular extension with abscess
      formation around the artificial valve. Treatment should be initiated promptly.
      High doses of antibiotics, tailored to the microorganism and the valve type
      (native or artificial valve), are administered intravenously during four, or more
      frequently, six weeks. In more than half of the patients cardiac surgery is also
      required. As soon as an indication for cardiac surgery is present, the operation
      should not be postponed. Experience learns that a smaller risk is associated with
      an early intervention. The operation is performed in a technically easier way.
      Eventually, also the total duration of hospitalization is shorter. Despite the
      available antibiotics and the technical progress in cardiac surgery, mortality
      remains high. This is the consequence of an increasing share of aggressive
      hospital germs, on the one hand, and an older population, characterized by a
      higher comorbidity, on the other hand.

PMID- 22482195
TI  - Component-resolved allergy diagnosis: a new era?
AB  - During the last decades a new in vitro technique has entered the field of allergy
      diagnosis, that is, component-resolved allergy diagnosis (CRD). In contrast to
      traditional specific IgE (sIgE) assays, CRD does not rely upon whole extract
      preparations from native allergens but on quantification of sIgE antibodies to
      single protein components, purified from natural sources or obtained by
      recombinant techniques. At present, it emerges that CRD can improve management of
      the allergic patient as it allows (to some extent) to discriminate between
      clinically significant and irrelevant sIgE result and to establish sensitization
      patterns with particular prognostic outcomes. Nevertheless, further clinical
      validation is mandatory before the technique can enter mainstream application. By
      no means can CRD currently be considered as a substitute to traditional sIgE
      assays.

PMID- 22482196
TI  - [Emergency guidelines for cosmetic procedures and esthetic skin treatment:
      recommendations of the medical establishment].
AB  - The use of devices for cosmetic treatment and esthetic skin treatments has
      increased in recent years. Some of these treatments, especially those that pass
      the dermo-epidermal barrier, can cause complications and secondary effects. In
      Belgium, there is almost no legislation concerning this type of treatment.
      Therefore, the Belgian Health Council has advised in a recent publication of
      January 2011, that there is an urgent need for adequate regulation concerning the
      use of devices for cosmetic treatment and esthetic skin treatment. The Council
      suggests to start up an evaluation commission, and also to have strict guidelines
      about the training needed for professionals who do this kind of treatments.
      Inspections by a competent authority should control the adherence to the
      forthcoming legislation.

PMID- 22482197
TI  - [Piet de Somer, the University of Leuven and the Belgium poliovaccine in 1956
      57].
AB  - In the years following WW II, all 'Western' countries were struck by recurrent
      epidemics of infantile paralysis (poliomyelitis). In the early 1950s, a vaccine
      developed by Jonas Salk in Pittsburgh, became available in the U.S. and Canada.
      In 1953-54 central virology laboratories in Sweden, Denmark and France were
      already well advanced in setting up local production lines of the vaccine. At
      that point in time, the Catholic University of Leuven, on the initiative of the
      young microbiology professor, Piet De Somer, and in collaboration with the
      pharmaceutical concern R.I.T. (Recherches et Industries Therapeutiques, Genval,
      Belgium), erected a new, multidisciplinary medical research institute, the Rega
      Institute. One of the research units to be headed by De Somer was destined to
      introduce the relatively new discipline of virology. As a test case, De Somer
      decided to venture on developing a production line of the Salk vaccine. In less
      than one year's time, the project was successful, such that Belgium became one of
      the first European countries to be self-supporting for its vaccine supply and to
      be able to initiate a large-scale vaccination campaign. The planning, preparation
      and execution of the project was accompanied by an extensive correspondence of De
      Somer with experts and other concerned parties in Belgium and abroad. This
      correspondence has been preserved and allows for a detailed reconstruction of the
      remarkable achievement.

PMID- 22482198
TI  - Focus on: minimally invasive dentistry.

PMID- 22482199
TI  - Do dentists practice medicine?

PMID- 22482200
TI  - It's 80-20 with biofilm: update on oral rinses.

PMID- 22482201
TI  - The modified grassline technique: a case report.

PMID- 22482202
TI  - Orange-yellow tongue and palate: case report.

PMID- 22482203
TI  - Follow the cosmetic pyramid for optimal aesthetic results.

PMID- 22482204
TI  - Integrating techniques to restore an adolescent's smile.

PMID- 22482205
TI  - Single file system: "the science of simplicity".

PMID- 22482206
TI  - Selecting a temporary cement: a case report.

PMID- 22482207
TI  - You can't always get what you want.

PMID- 22482208
TI  - In-office smile rehabs.

PMID- 22482209
TI  - The evidence-based decision path.

PMID- 22482210
TI  - Improving communication via digital technology.

PMID- 22482211
TI  - A brave new world of partnerships.

PMID- 22482212
TI  - The era of partnership is here.

PMID- 22482213
TI  - Partnerships for population health: the neighborhood health network.
AB  - Health reform is a major driver in shifting the focus toward population health.
      Partnerships between nurses, neighborhood health coaches (NHC), and families,
      linked by technology and extended over time, are key to enhancing neighborhood
      health. Including faculty practice and students in this work creates a new
      platform for nursing education in primary care; everyone wins.

PMID- 22482214
TI  - Clinical postconference pedagogy: exploring evidence-based practice with
      millennial-inspired "Building Blocks".
AB  - This article reports an innovative teaching strategy consisting of learning units
      whereby students come to postconference sessions prepared to share evidence-based
      practice (EBP) information associated with upcoming laboratory concepts, discover
      relationships among laboratory concepts and current nursing practice, and
      associate personal clinical experiences with the practice environment. This
      strategy, named "Building Blocks," represents one method to transform nursing
      education into a more active process, and also has the potential to prepare
      graduates who can function in a dynamic health care environment incorporating
      EBP.

PMID- 22482215
TI  - Exploring the changing landscape of jobs for new graduates: practice, education,
      and new graduate imperatives.
AB  - Numerous expert sources have reported a reduction in positions available for new
      graduate nurses, largely because of general economic conditions, although there
      are conflicting data and significant geographic variances. Nursing education,
      nursing practice, and new graduates themselves must develop partnerships to
      better prepare graduates for more challenging employment searches so that these
      newest members of the nursing workforce are retained and available for practice
      in preparation for the expected shortage of nurses in the near future.

PMID- 22482216
TI  - Confronting the barriers to health care reform.
AB  - Reforming health care is made more difficult when attention is successfully
      directed away from the root causes of increasing health care disparity and
      inflation. This article challenges nurses to accept an active role in health care
      reform as a part of professional responsibility.

PMID- 22482217
TI  - Application of the relationship-based care model to improve health outcomes via
      the electronic personal health record.
AB  - This article examines the metaparadigm of the relationship-based care (RBC) model
      in health care delivery, delineates selected characteristics of the electronic
      personal health record (ePHR), provides an example of how RBC applies to
      integration of the ePHR in the health care delivery setting, discusses the
      utility of RBC for interprofessional collaboration using the ePHR, and examines
      how application of RBC in conjunction with the ePHR has the potential to
      significantly improve patient outcomes.

PMID- 22482218
TI  - My yearlong journey with Victor: caring for an adolescent in medical crisis at a
      school-based health center.
AB  - This article discusses the multiple challenges faced by a seasoned pediatric
      nurse practitioner as she struggled to manage the medical complexities of a 13
      year-old boy in crisis while pushing the limits of her own professional
      boundaries-within the setting of an urban school-based health center (SBHC).

PMID- 22482219
TI  - Recipe for success: stories of evidence-based practice implementation.
AB  - Through a collaborative partnership with administrators at a university, nurse
      leaders at a local hospital worked to create a culture in which nurses could
      provide evidence-based practice (EBP). The Best Practice Series was started, and
      two participants' experiences of implementing EBP in their units are described
      with encouraging results.

PMID- 22482220
TI  - [Emergency criteria--walking a tightrope. Trauma teams should be registered and
      analyzes for better pre-hospital triage].

PMID- 22482221
TI  - [High diastolic pressure a warning sign in younger persons. The relevance of
      systolic and diastolic blood pressures differs between younger and older
      persons].

PMID- 22482222
TI  - [A hunter infected with tularemia following slaughter of a hare].

PMID- 22482223
TI  - [Activation of the trauma team is related to injury severity. Triage stringency
      can yield optimal use of resources].

PMID- 22482224
TI  - [Comparison Riks-HIA--medical records gave no basis for care improvement.
      Difficult to explain the lower number of reperfusion in ST elevation infarction
      in the Norrland's counties].

PMID- 22482225
TI  - [Screening for HIV and hepatitis C virus using saliva tests in a prison in Ghana.
      A study of the prevalence and the status of knowledge].

PMID- 22482226
TI  - [NSAID can increase the risk of cardiovascular incidents. The risk increase is
      usually connected to dosage and the length of treatment].

PMID- 22482227
TI  - [Evidence-based medicine: profit requirements makes health care worse and more
      expensive].

PMID- 22482228
TI  - [Foreign physicians in Swedish health care and the fight for integration in the
      Swedish (working)life].

PMID- 22482229
TI  - [Wrong diagnostic code makes the follow up of pregnant women's sick leave more
      difficult].

PMID- 22482230
TI  - [Ezra Pound--political prisoner disguised as mental patient].

PMID- 22482231
TI  - [Image of the month: Atypical evolution of a growing skull fracture].

PMID- 22482232
TI  - [Inadvertent implantation of a defibrillation lead in the left ventricle through
      a patent foramen ovale].
AB  - Inadvertent insertion of a defibrillation lead in the left ventricle is a rare
      complication generally underdiagnosed after device implantation. Management is
      not strictly codified due to the small number of observed cases. We report the
      case of a 78 year-old man in whom the diagnosis has been performed lately during
      an echocardiography.

PMID- 22482233
TI  - [Radiotherapy and urogenital Paget disease].
AB  - Urogenital Paget disease is usually treated by surgery. However, in case of
      recurrence or if multilating surgery is foreseen, radiotherapy seems to open a
      reasonable alternative. We report a successful treatment with radiotherapy in a
      patient with urogenital Paget's disease.

PMID- 22482234
TI  - [Metastatic melanoma: some hope from ipilimumab and vemurafenib].
AB  - Treating a patient with cutaneous malignant melanoma relies on the recognition of
      a clever stratification of the distinct stages of the disease. The
      histoprognostic criteria were recently revisited. In addition, translational
      research fueled the development of new treatments with at last increased efficacy
      in the metastatic stage. Such therapeutic advance improves the median overall
      survival for a few months. Some combined treatments could possibly boost the
      beneficial effects.

PMID- 22482235
TI  - [Statins and anesthesia: dilemma or obviousness? Is there still room for
      withdrawal of chronic statin therapy before surgery?].
AB  - Due to their action on the low-density lipoprotein-cholesterol (LDL-Cholesterol),
      statins efficiently take part in the treatment of coronary artery disease (CAD).
      Moreover, they exert various effects (called "pleiotropic") independently of
      their lipid lowering actions. All of these effects interact with inflammation,
      thrombosis and vasoconstriction during the perioperative period. However, statins
      may also increase the risk of rhabdomyolysis, a rare but potentially lethal
      complication. In this article, we will describe the advantages and disadvantages
      of statin therapy during the perioperative period. Although in the past,
      withdrawal of statins was recommended before anesthesia, there is now evidence
      that statins must be continued or even must be introduced before surgery. We will
      try to identify relevant situations were statins are still under-prescribed
      before surgery.

PMID- 22482236
TI  - [Psychomotor disadaptation syndrome: a poorly known clinical entity].
AB  - Psychomotor disadaptation syndrome is a typical geriatric clinical syndrome. It
      includes postural disorders such as body retropulsion, specific gait disorders,
      with axial akinesia and hypertonia, and psychobehavioral disorders akin to those
      found in depression. The diagnosis is essentially based on clinical observation
      rather than on iconographic data. This syndrome causes falls which induce a fear
      of falling. The old patient has a tendency to put himself down, to withdraw from
      society and to lose autonomy. This article briefly describes the physiopathology
      of the syndrome, recalls the diagnostic tools, and makes some suggestions
      regarding the care of patients suffering from this clinical entity.

PMID- 22482237
TI  - [Proven and expected benefits of intravenous lidocaine administered during the
      perioperative period].
AB  - Local anesthetics which inhibit sodium channels are used for neural blockade
      during infiltration and locoregional anesthesia. Furthermore lidocaine given
      intravenously acts on other cellular systems and produces multiple properties,
      some of which are beneficial during the perioperative period. Indeed, intravenous
      lidocaine is analgesic, antihyperalgesic, antiinflammatory, and improves the
      recovery of bowel function after abdominal surgery. As a consequence, lidocaine
      has been added to postoperative analgesic strategies. This article reviews
      clinically relevant properties of intravenous lidocaine. Its future perspectives
      for the prevention of chronicisation of postoperative pain, facilitation of
      postoperative fast track programs, and prevention of tumoral recurrence are also
      discussed.

PMID- 22482238
TI  - [Neurostimulation: which place in the treatment of refractory headaches?].
AB  - The management of refractory headaches (migraine or cluster headache) is often
      challenging in clinical practice. Most of the time, these patients are
      "desperate" and have already tried all existing medications. Many progresses have
      recently been made in the therapeutic approach of these diseases, especially with
      the advent of neurostimulation techniques. In this review of the literature, we
      describe various neurostimulation methods which have been studied in clinical
      trials or case reports of refractory headaches. The most effective and best
      studied methods are occipital nerve stimulation (ONS) and hypothalamic deep brain
      stimulation (DBS), the latter being however at higher surgical risk. Hence, there
      is a new hope for patients with refractory headaches. Various clinical trials are
      still underway.

PMID- 22482239
TI  - [Linagliptin (Trajenta): a selective DPP-4 inhibitor with limited renal
      elimination].
AB  - Linagliptin (Trajenta) is a selective inhibitor of dipeptidyl peptidase-4, an
      enzyme that degrades two incretin hormones, GLP-1 ("Glucagon-Like Peptide-1") and
      GIP ("Glucose-dependent Insulinotropic Polypeptide"). As other molecules
      belonging to this pharmacological class, linagliptin improves blood glucose
      control of type 2 diabetic patients, without increasing hypoglycaemic risk,
      without promoting weight gain and with a good clinical and biological tolerance
      profile. Both efficacy and safety have been demonstrated in randomized controlled
      trials as monotherapy or in combination with other glucose-lowering agents,
      independent of demographic or clinical patient's characteristics. The
      pharmacokinetics specificity of linagliptin comprises its biliary excretion, with
      low hepatic metabolism (no drug-drug interactions) and, in contrast to other
      gliptins, its negligible renal elimination. Because of these favourable
      properties, linagliptin may be used without dose adjustment (5 mg once a day) in
      patients with renal impairment, as well as in elderly people.

PMID- 22482240
TI  - [Which HbA1c and lipid targets in patients with type 2 diabetes?].
AB  - Patients with type 2 diabetes are at high cardiovascular risk and require a
      global management targeting all risk factors. Target values for blood pressure
      have been discussed in a previous paper. The present clinical case summarizes the
      most important arguments concerning the choice of the target values for glucose
      control (glycated haemoglobin or HbA1c) and lipid management. As far as glucose
      control is concerned, the objective should be individually adjusted, based on the
      benefits/risks ratio, with a less stringent HbA1c level in presence of coronary
      heart disease and risk of severe hypoglycaemia. However, in absence of these two
      risks factors, the objective should be reinforced (HbA1c < 7%), essentially to
      prevent or retard microangiopathic lesions. As far as lipid management is
      concerned, the most crucial goal remains LDL cholesterol lowering, with a target
      value < 100 mg/dL in patients at high cardiovascular risk and <70 mg/dL in
      patients at very high risk, according to the recent European guidelines.
      Dyslipidaemia related to the metabolic syndrome (hypertriglyceridaemia, low HDL
      cholesterol) may also represent a therapeutic target (non-HDL cholesterol),
      although evidence is mostly missing in the literature.

PMID- 22482241
TI  - A description of a specialist led primary care based oral surgery service.
AB  - AIM: To describe the establishment of a referral only oral surgery service in a
      primary care setting together with the challenges, benefits and successes of the
      service. PROBLEM: In 1994 waiting times for hospital for oral surgery and
      maxillofacial procedures were unacceptably long. A proposal to establish a
      primary care oral surgery service aimed to complement the hospital-based service,
      reduce treatment delays. OUTCOME: Referrals commenced immediately in response to
      a managed launch with local dentists recognising the service as a source of
      expedient and convenient treatment for their patients. The service now treats up
      to 1300 patients per year. LEARNING POINTS: New dental services to dentistry can
      encompass different specialities. Initial capital investment is needed to develop
      a more cost-effective service. Recruitment of suitable specialist staff is a
      critical for success. Staffing, organisation and funding must be sustained.

PMID- 22482242
TI  - The caries experience of 11 to 12 year-old children in Scotland and Wales and 12
      year-olds in England in 2008-2009: reports of co-ordinated surveys using BASCD
      methodology.
AB  - OBJECTIVE: This paper brings together summarised findings on surveys of 106,828
      mainstream school pupils aged 11-12 years old undertaken in Scotland, Wales and
      England in 2008/09. These surveys are the latest in a series using common
      criteria for measurement and a range of consent arrangements which, for this age
      group, allow comparison between the three "countries" and over time. METHOD:
      Representative samples were drawn within the geographies of primary care
      organisations in the three countries and within English Local Authorities
      according to BASCD criteria for sampling. Consent was sought from pupils in Wales
      and England and passive consent was used in Scotland. Children aged twelve were
      examined in England and children in school year 7 (rising 12) were examined in
      Wales and Scotland. Examinations were conducted in schools by trained and
      calibrated examiners using BASCD standard criteria and caries was diagnosed at
      the dentinal threshold using visual criteria. RESULTS: The trend for reducing
      caries prevalence and severity continues in this age group in all three
      countries. Unlike data for 5 year old children, the impact of seeking positive
      consent from pupils does not appear to have introduced bias into the results.
      Variation in caries levels between and within geographical areas continues.
      CONCLUSION: Caries prevalence surveys of children aged 11-12 years have been
      conducted across Great Britain. Those carried out with positive consent appear to
      produce unbiased results, comparable with previous surveys. Health inequalities
      in this age group persist, as does the burden of disease for those with end-stage
      caries.

PMID- 22482243
TI  - Assessment of caries experience in epidemiological surveys: a review.
AB  - OBJECTIVES: To review aspects of methods for assessing caries experience (CE) in
      epidemiological surveys. METHOD: A search of English language literature
      published between January 2000 and December 2008 was undertaken using
      'epidemiology', 'dental caries' and 'assessment' as search terms. Information on
      criteria for CE assessment, materials and settings, diagnostic threshold,
      training of examiners and validation of the screening results was extracted from
      the reports. RESULTS: Eighty-nine reports met the inclusion criteria. In 9 of the
      reports (10%) no reference was made to existing standardisation criteria for
      assessment of CE. Light condition applied (60 reports, 67%) and the use of a
      probe (60 reports, 67%) were frequently reported. Most reports mentioned that
      training and calibration of examiners took place, but the outcome of reliability
      checks were often not presented (48 reports, 54%). Only 28 of the reports (32%)
      specified that cleaning took place before the examination. Journals with Impact
      Factor (IF) provided specific information on methods more frequently than
      journals without. The WHO Basic Methods for Oral Health Surveys were most often
      applied (52 surveys, 58%). However, deviations from the original description were
      found especially for measurement and reporting of reliability measurement (24,
      46% and 29, 56% respectively), type of probe used (27, 52%) and light condition
      (16, 31%). All of these hamper the (external) validity of the obtained results.
      CONCLUSIONS: There is a clear need for improvement of the reporting and
      application of methods for assessing CE in epidemiological surveys. A check-list
      of aspects of methods to be included in reports of surveys assessing CE is
      proposed by the authors.

PMID- 22482244
TI  - Dental caries experience among 12-year-old children in Northwest Russia.
AB  - OBJECTIVE: To estimate the prevalence and experience of dental caries among 12
      year-olds in Northwest Russia. METHODS: Altogether 355 schoolchildren at the age
      of 12 were selected at random from 3 urban and 4 rural areas in the Arkhangelsk
      region. Girls comprised 53.7% of the sample. Caries experience was assessed at D3
      level by a single calibrated examiner. The prevalence of caries was estimated
      with 95% confidence intervals (CI) using Wilson's method. Caries experience was
      estimated using DMFT index and presented as means and 95% CIs. Dichotomous and
      numerical data were analysed by chi-squared tests and Mann-Whitney tests,
      respectively. RESULTS: The prevalence of caries was 83.4% (95% CI 79.2-86.9) with
      the mean DMFT of 2.95 (95% CI 2.70-3.20). On average, there were 1.56 (95% CI
      1.37-1.76) decayed, 0.03 (95% CI 0.01-0.06) missing and 1.34 (95%CI 1.16-1.52)
      filled teeth. No gender differences in the prevalence of caries in any of the
      settings or in the full sample were observed. The overall caries experience was
      higher in urban than in rural areas (3.38 vs. 2.64, p = 0.001). The mean number
      of decayed teeth in urban areas was lower (1.29 vs. 1.77, p = 0.009), but the
      number of filled teeth was greater (2.02 vs. 0.85, p = 0.001) than in rural
      areas. CONCLUSIONS: The prevalence and experience of caries among 12-year-olds in
      the Arkhangelsk region is greater than in most European countries. Urgent public
      health measures at both population and individual levels are needed to improve
      the situation.

PMID- 22482245
TI  - Variations in caries diagnoses and treatment recommendations and their impacts on
      the costs of oral health care.
AB  - OBJECTIVE: To evaluate the reproducibility of caries detection and treatment
      planning among public health dentists and estimate the possible impact of their
      decisions on financial costs. RESEARCH DESIGN AND SETTINGS: Thirty nine dentists
      working in the public health service of Piracicaba, Sao Paulo, Brazil made a
      combined visual-radiographic caries examination of 40 occlusal surfaces of
      extracted permanent teeth mounted on two dental mannequins and proposed treatment
      plans for each tooth. Histological validation then evaluated the diagnoses
      validity and the suitability of the treatment plans. OUTCOME MEASURES: Inter
      examiner agreement was calculated by Cohen's Kappa statistics. The sensitivity
      and specificity of caries detection and treatment decision were calculated. The
      costs of dental treatment plans for public health system were calculated from a
      Brazilian public health service fee scale. RESULTS: Inter-examiner agreement for
      caries detection was moderate (kappa = 0.42) while for treatment decisions it was
      fair (kappa = 0.29). The sensitivity and specificity were 0.69 and 0.65 for
      caries detection and 0.56 and 0.65 for treatment decision respectively. Dentists
      overestimated the presence and depth of carious lesions and there was a tendency
      to treat enamel lesions using invasive therapeutic procedures. Mean treatment
      cost across the two cases was 32US$ (range 9-65) while the histologically
      validated cost was 23US$. CONCLUSION: The variability in caries detection and
      treatment decision negatively affected the cost of the dental treatment.

PMID- 22482246
TI  - Caries prevalence of 5, 12 and 15-year-old Greek children: a national pathfinder
      survey.
AB  - AIM: To study the caries prevalence and caries experience of 5, 12 and 15-year
      old children in Greece and evaluate how the disease pattern is related to their
      sociodemographic parameters. METHODS: A stratified cluster sample of 1209, 1224
      and 1257 of five, twelve and fifteen-year-old Greek children were randomly
      selected according to WHO guidelines for national pathfinder surveys and examined
      for dental caries, according to the BASCD criteria and standards. d3mft, D3MFT
      and their components, as well as d3mfs, D3MFS, Care Index (CI) and SiC were
      recorded and related to the demographic data collected concerning age, gender,
      counties, urban/rural areas and parents' educational status. RESULTS: Dental
      caries varied considerably between the different districts, with a mean dmft/DMFT
      value for each age group being 1.77, 2.05 and 3.19 respectively, while 64%, 37%
      and 29% of them, were with no obvious dentinal caries. Children living in rural
      areas demonstrated significantly higher dmft/DMFT values and less dental
      restorative care (CI), whereas children with fathers of a higher educational
      level showed significantly lower dmft/DMFT values. The significant caries (SIC)
      index value for the three age groups was 5.01, 4.83 and 7.07 respectively.
      Posterior occlusal surfaces of the permanent teeth presented most of the caries
      in the 12 (68%) and 15-year-old group (78%). CONCLUSIONS: Despite the decrease in
      the prevalence of caries in Greek children disparities remain. Children in rural
      areas and children with less educated parents had more caries and more untreated
      caries. All the above call for immediate intervention with comprehensive
      preventive programs and better geographic targeting of the dental services at a
      national level including targeted prevention of pit and fissure sealants on
      posterior permanent molars.

PMID- 22482247
TI  - Associated factors of tooth wear among Malaysian 16-year-olds: a case-control
      study in Kota Bharu, Kelantan.
AB  - OBJECTIVE: To determine the associated factors of tooth wear (TW) among 16-year
      old school children. METHOD AND MATERIALS: A random selection of secondary school
      children from 8 government secondary schools in Kota Bharu, Kelantan, Malaysia,
      participated in this case-control study. The Smith and Knight Tooth Wear Index
      and WHO criteria were used to chart tooth wear and dental caries respectively.
      Saliva analyses used standards recommended by GC Asia Dental. Self-administered
      questionnaire provided socio-demographic profile of the family, general knowledge
      of tooth wear, oral hygiene, food and drinks practices and other associated
      variables for tooth wear. Analysis using multiple logistic regression was
      performed. RESULTS: Of the 576 children sampled, 40% of the 460 controls were
      male as were 57% of the 116 in the case group. Multivariate analysis showed
      gender, monthly household income, carbonated drinks, caries experience, pool
      swimming, duration of intake of orange juice and hydration rate and viscosity
      were significantly associated with wear. CONCLUSION: The factors associated with
      tooth wear were similar to those encountered in other studies. Oral health
      promotion activities should emphasise those factors which can be changed. The
      erosive potential of some foods and drinks require further investigation.

PMID- 22482248
TI  - Factors associated with self-assessed masticatory ability among community
      dwelling elderly Japanese.
AB  - Self-assessed masticatory ability has been shown to be significantly related to
      general health among elderly persons. OBJECTIVE: To identify oral factors
      associated with the self-assessed masticatory ability. BASIC RESEARCH DESIGN:
      Cross-sectional study. PARTICIPANTS: A total of 736 community-dwelling elderly
      persons. MAIN OUTCOME MEASURES: Data on background factors and the self-assessed
      masticatory ability were collected by questionnaire. An intraoral examination
      examined the pattern of posterior occluding pairs of natural teeth (POPs), the
      WHO Community Periodontal Index of Treatment Needs (CPI) and denture-related
      factors such as use of dentures, pain when using dentures and stability and
      retention of dentures. Chi-squared tests examined the relationships between the
      self-assessed masticatory ability and the background factors and oral conditions.
      Ordinal regression models were constructed with the self-assessed masticatory
      ability as the dependent variable and oral conditions as the principal
      independent variables, to adjust for the potential confounding variables.
      RESULTS: Self-assessed impairment of masticatory ability was associated with lost
      POPs (p < 0.001) and CPI (p = 0.012). In the participants with lost POPs, self
      assessed impairment of masticatory ability was associated with not using dentures
      and pain when using dentures (p < 0.001). In the totally edentulous subjects,
      impairment of masticatory ability was not associated with stability and retention
      of dentures (p = 0.070). CONCLUSIONS: Factors affecting self-assessed masticatory
      ability include the pattern of POPs, periodontal status, denture use and pain
      when using dentures.

PMID- 22482249
TI  - The use of occlusal indices in high-impact literature.
AB  - Malocclusion is difficult to define because individuals and cultures vary widely
      in their perceptions of what constitutes an occlusal problem. A number of
      occlusal indices have been devised but, probably because of this perceptual
      problem, none has ever emerged as a standard. OBJECTIVE: The main objective was
      to review the use of the principal occlusal indices. BASIC RESEARCH DESIGN: The
      PUBMED database was searched for the main occlusal indices employed, journals
      with an impact in dentistry and specialist orthodontics journals. RESULTS: The
      occlusal indices most frequently employed were IOTN (163 studies), PAR (132
      studies), DAI (68 studies) and ICON (32 studies). The journals publishing the
      greatest number of studies using these occlusal indices are those specialising in
      orthodontics. CONCLUSIONS: In the high-impact scientific literature, the indices
      in greatest use are IOTN, followed by PAR, DAI and ICON. DAI and IOTN are mainly
      used in epidemiological or prevalence studies, while PAR is generally used for
      longitudinal studies. IOTN is used more in Europe. DAI is used worldwide; though
      least in Europe.

PMID- 22482250
TI  - Oral health status of a group of illicit drug users in Delhi, India.
AB  - OBJECTIVES: To assess the oral health and related practices of a group of illicit
      drug users in Delhi, India; to compare with that of non-drug users; and to assess
      the impact of illicit drug use on oral health. DESIGN: Cross-sectional study.
      Comparison was made with non-drug users to investigate any differences in oral
      health between illicit drug users and general population. SETTING AND
      PARTICIPANTS: Illicit drug users attending a drug dependence treatment clinic in
      Delhi (n=126). Equal number of non-drug users attending other outpatient
      departments in the same setting. OUTCOME MEASURES: Oral health practices assessed
      using structured questionnaire; dental caries, periodontal status and oral mucosa
      assessed using World Health Organization 2004 criteria; oral hygiene assessed
      using OHI-S. RESULTS: Mean DMFT and OHI-S scores amongst the drug users were 3.48
      and 3.80, respectively. Bleeding, shallow pockets and deep pockets were found as
      the highest CPI finding in 42%, 44% and 12% of drug users respectively.
      Premalignant states of leukoplakia and OSMF were diagnosed in 13% and 4% of drug
      users respectively. Significant differences were found between drug users and non
      drug users with respect to oral hygiene practices; DMFT, OHI-S, CPI scores; and
      leukoplakia. In multivariate analysis, illicit drug use was significantly
      associated with CPI highest score (OR = 2.21, 95% CI 1.08-4.52). CONCLUSION: The
      illicit drug users had significantly poorer oral hygiene practices, oral hygiene
      and periodontal health; higher caries experience; and higher prevalence of
      leukoplakia as compared to non-drug users. The findings of the study suggest that
      illicit drug use is independently associated with poor periodontal health.

PMID- 22482251
TI  - Promoting positive health behaviours--'tooth worm' phenomenon and its
      implications.
AB  - 'Tooth worm' is a traditional belief about the pathogen of dental caries (tooth
      decay). Nevertheless, in our previous study, parental 'tooth worm' belief was
      linked to a reduced caries risk of their children. OBJECTIVES: This study aimed
      to further characterize the impact of parental 'tooth worm' belief on their
      children's caries experience and its psychobehavioural mechanisms. BASIC RESEARCH
      DESIGN: analytic observational study. SETTING: Thirteen randomly selected
      kindergartens in Singapore. PARTICIPANTS: 1,782 preschoolers aged 3-6 years.
      METHODS: Each child received an oral examination and microbiological tests.
      Parents completed a self-administered questionnaire on their socio-demographic
      background, oral health knowledge/attitude and child's oral health habits.
      RESULTS: Multivariate analysis confirmed a reduced chance of 'high caries rate'
      (number of affected teeth > 2) among children whose parents held the 'tooth worm'
      belief (Odds Ratio = 0.41; 95% Confidence Interval = 0.19-0.89). With such
      perception among parents, children brushed their teeth more frequently (p =
      0.042). Since no difference in oral hygiene was observed, the health benefit of
      the "tooth worm" perception may be acquired through the delivery of fluoride (an
      agent with proven anti-caries effect) during frequent toothbrushing episodes.
      CONCLUSIONS: This study revealed a 'tooth worm' phenomenon, indicating that
      parental 'tooth worm' belief is associated with early establishment of regular
      toothbrushing habit and reduction of dental caries in children. This phenomenon
      and its psychobehavioural mechanisms, enriching our understanding of oral health
      behaviours, have implications for effective health education.

PMID- 22482252
TI  - Development and testing of a theory-based behavioural change intervention: a
      pilot investigation in a nursery school in a deprived area of Scotland.
AB  - OBJECTIVE: Investigate the effect of a theory-based intervention on oral-health
      knowledge, attitudes and behaviours of early years staff (EYS), parents and
      nursery children. METHODS: Qualitative research with staff and parents from eight
      nurseries through interviews/focus groups. An intervention was developed and
      piloted using pre-posttest design. CLINICAL SETTING: Nurseries in deprived
      communities in Dundee, Scotland. PARTICIPANTS: 111 children aged 3-5 years
      attending nursery, including 79 parents and 8 nursery staff. INTERVENTIONS: Staff
      session targeted outcome expectancies, subjective norms and self-efficacy for
      tooth-brushing in nursery using information provision, modelling and goal
      setting, followed by a three-week intervention. Parent-child dyads received a
      leaflet with instructions for goal-setting, planning and monitoring home
      brushing. Tooth-brushing self-monitoring materials (e.g. two-minute timer,
      diaries) were used and certificates provided in the nursery as rewards. OUTCOME
      MEASURES: EYS knowledge, attitudes and behaviours were assessed before and after
      the intervention using self-report questionnaires. Parents completed interviews
      assessing beliefs about tooth-brushing and their children's tooth-brushing
      behaviour at baseline and post-intervention follow-up. RESULTS: Significant
      improvements in staff knowledge, but not attitudes, self-efficacy, or nursery
      tooth-brushing were reported. Parent-child dyads completing the intervention were
      not more likely to report their child carried out twice-daily tooth-brushing at
      home. The intervention did not improve parents' intentions to brush their child's
      teeth twice a day or beliefs about the ease of twice-daily tooth-brushing.
      CONCLUSION: Only past behaviour significantly predicted posttest brushing.
      Parents who found brushing easier at baseline were more likely to complete the
      intervention. Recommendations are made regarding implementing psychological
      theory and methods into oral-health interventions.

PMID- 22482253
TI  - The oral health status of special olympics athletes in Belgium.
AB  - OBJECTIVES: To describe and evaluate the oral condition and oral treatment needs
      of the participants of the Special Olympics Special Smiles program organised in
      Belgium in 2008. DESIGN: A cross-sectional study where the data were collected
      through interviews and clinical examinations. PARTICIPANTS: 687 Belgian Special
      Smiles athletes participated, mean age 33 years. RESULTS: More than 70% had at
      least one missing tooth. Distinct signs of gingivitis and visible caries
      experience were observed in 44% and 22% of dentate athletes respectively. Dutch
      speaking athletes were less likely to present with untreated caries (OR: 0.46;
      95% CI: 0.31-0.68) or with gingivitis (OR: 0.51; 95% CI: 0.37-0.71) compared to
      their French-speaking colleagues. Signs of past injury were identified in 12% of
      athletes. Of those athletes with an edentulous mandible, only 53% presented with
      a removable denture; 73% of athletes missing some maxillary anterior teeth and
      30% of those missing all anterior teeth had no prosthetic replacement in the
      maxilla. Nearly two fifths of athletes were referred for treatment: in 12% of
      athletes dental treatment was considered urgent. CONCLUSION: The results suggest
      that there is a tremendous unmet need for dental treatment in the Belgian Special
      Smiles population, with French-speaking athletes in greatest need. Improvements
      in data collection should be encouraged for example. more detailed screening
      methods (e.g. caries screening including enamel lesions, full periodontal
      examination) and questionnaires (e.g. inclusion of questions related to dietary
      habits, dental attendance). In this way barriers to optimal oral health (care) in
      this population could be further explored, attempts made to reduce them and so
      reduce health inequalities.

PMID- 22482254
TI  - Coincidence and awareness of oral parafunctions in college students.
AB  - OBJECTIVE: The aim of the study was to determine the prevalence and awareness of
      particular types of oral parafunctions in young healthy students and any
      association with temporomandibular disorders (TMD). MATERIAL AND METHODS: The
      study was performed in a randomly selected group of 303 healthy students (mean
      age 18.8 years) from the vocational technical school in Wroclaw, Poland, who
      underwent a routine clinical examination and functional analysis of the mouth. On
      taking the history all subjects were asked about their awareness of various forms
      of parafunctional activity in their mouth. RESULTS: Almost all subjects revealed
      various oral parafunctions such as: bruxism, nail and pen biting, chewing gum,
      and biting the mucosa of lip or cheek. These habits were present singly or as
      double, triple or even fourfold coincidences in a single person. The most
      frequent oral parafunctions were habitual gum chewing and bruxism. Subjects were
      very seldom aware of the last parafunction. TMDs were more prevalent in the
      presence of bruxism than in other oral parafunctions. CONCLUSIONS: The studied
      students revealed various types of oral parafunctions, however most of them were
      not aware of clenching and grinding their teeth.

PMID- 22482255
TI  - Illness-related behaviour and sociodemographic determinants of oral health care
      use in Dabou, Cote d'Ivoire.
AB  - OBJECTIVES: The aims of this study were to describe adults' oral health behaviour
      and identify the sociodemographic determinants that influence people to seek oral
      care in Cote d'Ivoire, in a context of promoting a more accessible health care
      system. METHODS: The design was a cross-sectional pilot survey undertaken in the
      department of Dabou, Cote d'Ivoire. A stratified sampling procedure with
      proportional allocation size was used, based on four different criteria: place of
      residence; type of dwelling; distance between the chosen locality and the dental
      clinic; and, the presence of a medical centre in the locality. The sample
      consisted of 927 people (18 years or older) who were interviewed by
      questionnaire. Data were collected at face to face interviews, using the method
      of itineraries. RESULTS: 34% of the population had not accessed a dental
      practitioner during the past 12 months. The reasons for not seeking care were:
      self-medication, lack of money and a perception of not needing care. A dentist or
      a traditional healer had been sought by 33%. The choice of therapy was influenced
      by educational level and having health insurance (p < 0.05). The main reasons for
      attending a traditional healer were linked to educational level, the type of
      dwelling and the participants' place of residence (p < 0.05). Choosing to see a
      dentist was associated with age, the type of dwelling and the distance between
      the chosen locality and the dental clinic (p < 0.05 CONCLUSION: The socioeconomic
      situation of the participants was a determining factor for seeking care.
      Improving access to health care should be part of the global fight against
      poverty and the reduction of social inequalities.

PMID- 22482256
TI  - Number of teeth and its association with central obesity in older Southern
      Brazilians.
AB  - Evidence suggests that older adults with extensive tooth loss may present
      dietetic restrictions and frequently choose softer and more processed foods,
      which consequently may lead to obesity. OBJECTIVE: To evaluate whether there was
      an association between dental status and central obesity in community-dwelling
      elderly. BASIC RESEARCH DESIGN: A simple random sample of 471 community-dwelling
      Brazilian elderly ranging from 60 to 89 years old was evaluated in 2006. A
      questionnaire on socio-demographic, behaviour, general and oral health variables
      was applied. The number of natural teeth and the use of dental prostheses,
      following the World Health Organization (WHO) criteria, were assessed. MAIN
      OUTCOME MEASURES: The circumferences of the waist and the hip were measured in
      order to provide the waist circumference (WC) and the waist-hip ratio (WHR)
      measures. For both measures, participants were categorised as non-obese or obese
      according to the WHO-established cut-off points. RESULTS: Participants with more
      than 8 teeth were less likely to have central obesity, as measured by WHR [OR =
      0.49 (0.32 to 0.87)], while participants with only 1-8 natural teeth were more
      likely to have central obesity when evaluated by WC [OR = 3.28 (CI 1.43 to
      7.52)]. CONCLUSIONS: Tooth loss was associated with central obesity, even when
      controlled for confounders, suggesting a relationship between oral health status
      and nutritional status in this sample of community-dwelling Brazilian elderly.
      Preserving natural teeth may have a positive impact on the nutritional status of
      older adults and on obesity-related morbidity.

PMID- 22482257
TI  - Perception of oral health related quality of life (OHQoL-UK) among periodontal
      risk patients before and after periodontal therapy.
AB  - OBJECTIVE: To assess the oral health related quality of life among periodontal
      risk patients before and after periodontal therapy. METHOD: The study population
      consisted of 183 patients reporting to the outpatient department of periodontics,
      who were grouped into low, moderate and high risk patients based on the
      periodontal risk assessment model. The patients were asked to complete the OHQoL
      UK 16 questionnaire before and after periodontal therapy. The change in the
      patient perception of quality of life before and after treatment was assessed.
      RESULTS: Periodontitis had a considerable negative impact on the quality of life
      of patients in the high risk group in comparison to low and moderate risk groups
      (p < 0.001). Treatment brought about an improvement in the OHQoL scores in the
      moderate and high risk group. CONCLUSION: This study shows that risk of
      periodontal disease is significantly related to oral health related quality of
      life and periodontal therapy improves the quality of life of patients.

PMID- 22482258
TI  - Dental fluorosis, dental caries, and quality of life factors among schoolchildren
      in a Colombian fluorotic area.
AB  - OBJECTIVE: To assess dental fluorosis, dental caries and quality of life factors
      associated with dental fluorosis among schoolchildren living in a Colombian
      endemic dental fluorosis area. METHOD: 110 12-year olds were visually examined
      for dental caries (ICDAS) and dental fluorosis (TF) and a self-administered
      quality of life and fluorosis questionnaire was applied. RESULTS: The prevalence
      of dental fluorosis reached 100% in this sample with most children falling within
      the TF 3 severity category. Varying degrees of severity were observed as follows
      for TF 1 to 6: 1%, 16%, 62%, 16%, 4%, 2%. The prevalence of caries experience (DF
      S2) was 54%. The DF-S2 mean was 4.4 (sd 4.3). The principal contributor to the DF
      S2 outcome was the decayed component. When initial caries lesions were included
      (ICDAS-scores 1-3) the mean DF-S1,2 increased to 10 (sd 5.1). The association
      between fluorosis and dental caries was not statistically significant (p > 0.05).
      Children not only detected the presence of something abnormal in their teeth but
      also reported feeling embarrassed, and worried due to their dental appearance.
      Almost 60% of the children reported avoiding smiling because of their teeth's
      appearance. CONCLUSIONS: The high prevalence of dental fluorosis and dental
      caries combined with the schoolchildren's negative perception about their dental
      health reflects the need to propose effective dental public health policies to
      regulate multiple exposures to fluoride at an early age, and to improve health
      outcomes in a highly vulnerable population.

PMID- 22482259
TI  - Relationship of periodontal disease to pre-term low birth weight infants in a
      selected population--a prospective study.
AB  - OBJECTIVE: To assess effect of periodontal status of antenatal mothers on
      pregnancy outcomes in a selected population in Malaysia. DESIGN: Prospective
      cohort study on a multi-ethnic convenient sample. METHODS: 73 healthy pregnant
      women between 28 to 36 gestation weeks attending 5 ante-natal centres were
      recruited. Both Interviewer-administered Questionnaire and Periodontal
      examination, which included Plaque index, Gingival index, Papillary Bleeding
      index, probing pocket depth and attachment loss were conducted. OUTCOMES:
      Pregnancy outcome data which included gestational age at delivery, birth weight
      of newborn and delivery complications were collected after delivery. RESULTS:
      Study sample of 73 mothers was approximately in 1:3 case:control ratio (21.9% &
      78.1% respectively). Case was defined as those with preterm (PT) deliveries and
      low birth weight (LBW) infants whereas control was otherwise. 37 pregnant women
      were diagnosed with periodontal disease (minimum 2 teeth with > or = 5 mm
      periodontal pockets and > or = 3 mm attachment loss) and 36 without periodontal
      disease (PD). Of those with PD, 4 (10.8%) had PT delivery and 3 (8.1%) had LBW
      infants. None of the PD variable means or PD status associated significantly with
      either of the two groups (P>0.05). Logistic regression analysis to test the
      possible predictor (demographic and clinical) for PT or LBW status indicated only
      Plaque Index mean as a significant predictor (P < 0.03). CONCLUSIONS: In this
      study population, PD was not shown to be a risk factor for PT delivery or LBW
      infant. Only mean Plaque Index was associated with PT deliveries and LBW infants.

PMID- 22482260
TI  - Dental enamel defects in Italian children with cystic fibrosis: an observational
      study.
AB  - OBJECTIVE: The relationship between cystic fibrosis (CF) and caries experience
      has already been explored, but relatively little information is available on
      dental enamel defects prevalence among children affected by cystic fibrosis. The
      aim of this study was to investigate this issue in deciduous and permanent teeth
      of children with CF resident in southern Italy. BASIC RESEARCH DESIGN: This cross
      sectional observational study was undertaken between October 2009 and March 2010.
      PARTICIPANTS: 88 CF patients and 101 healthy age-matched participated in this
      study. METHODS: The prevalence of dental enamel defects was calculated using a
      modified Developmental Defects of Enamel (DDE) index. The comparison of dental
      enamel defects prevalence among groups was carried out using regression binary
      logistic analysis. RESULTS: In the CF subjects there was a higher prevalence
      (56%) of enamel defects in comparison to the healthy group (22%). The most
      prevalent enamel defect was hypoplasia with loss of enamel (23% of CF patients vs
      1 1/2% of control group) in permanent teeth. CONCLUSION: This study confirms that
      children with cystic fibrosis are at increased risk of developing hypoplastic
      defects on their permanent teeth.

PMID- 22482261
TI  - Orofacial pain symptoms and associated disability and psychosocial impact in
      community-dwelling and institutionalized elderly in Hong Kong.
AB  - OBJECTIVE: The study investigated the experience of orofacial pain (OFP) symptoms
      and associated disability and psychosocial impact in community dwelling and
      institutionalized elderly people in Hong Kong. METHODS: A community-based cross
      sectional survey involving elders aged 60 years and above. Participants were
      recruited at social centres for the elderly and homes for the aged throughout
      Hong Kong. Elders who reported OFP symptoms in the previous four weeks took part.
      Standard questions were asked about OFP conditions in the previous month and the
      Manchester Orofacial Pain Disability Scale (MOPDS), the Oral Health Impact
      Profile (OHIP-14) and the General Health Questionnaire (GHQ-12) were
      administered. The MOPDS was translated and validated for use in Chinese elders.
      RESULTS: 200 community dwelling and 200 institutionalized elders participated.
      Toothache was the most common symptom (62.0%) and burning sensation in the tongue
      was least common (0.5%). The distribution of pain symptoms, pain duration and
      severity and pain ratings were similar in both groups. The MOPDS (Chinese elders
      version) had good reliability and construct validity. The MOPDS and OHIP-14
      summary scores was significantly higher in the institutionalized elderly (p <
      0.001 and p < 0.013, respectively). Psychological distress (GHQ-12 score > or =
      4) was more common among the institutionalized elderly (11%) than the community
      dwelling elderly (4.0%, p = 0.002). CONCLUSIONS: Orofacial pain symptoms were
      associated with significant disability and had a detrimental impact on
      psychological distress level and quality of life, particularly in the
      institutionalized elderly. There is a need to improve access to professional care
      and health-related outreach services generally for elderly people in Hong Kong.

PMID- 22482262
TI  - Association of hyposalivation with oral function, nutrition and oral health in
      community-dwelling elderly Thai.
AB  - OBJECTIVES: This study was to analyze the association of hyposalivation with oral
      function, nutritional status and oral health in community-dwelling elderly Thai.
      METHOD: The subjects were 612 elderly people (mean age = 68.8, SD 5.9 years).
      Oral function (tasting, speaking, swallowing and chewing) and Mini Nutritional
      Assessment (MNA) were evaluated. Oral examination investigated teeth and
      periodontal status. Both unstimulated and stimulated whole saliva were collected
      for 5 minutes. RESULTS: Among all subjects, 14.4 % were classified within the
      hyposalivation. Hyposalivation was associated with gender, systemic disease,
      medication, and smoking. Subjects within the hyposalivation group had a higher
      number of decayed teeth and a higher prevalence of periodontitis than the normal
      salivation group (p < 0.05). The hyposalivation group also had a lower number of
      teeth present and a lower mean MNA score than the normal salivation group (p <
      0.05). Logistic regression analysis showed that hyposalivation in both dentate
      and edentulous subjects was significantly associated with tasting, speaking,
      swallowing and chewing. CONCLUSION: This study suggested that hyposalivation is a
      risk factor not only for dental caries and periodontal disease but also for taste
      disturbances, speaking problems, swallowing problems, poor chewing ability and
      malnutrition. Monitoring salivary flow is an important measure in the care of
      older people.

PMID- 22482263
TI  - Assessment of the relationship between perceptions of dental aesthetics and
      demand for orthodontic treatment in 10-11 year old school children in Birmingham,
      UK.
AB  - OBJECTIVE: To examine the relationship between perceptions of dental aesthetics
      and demand for orthodontic treatment, and to determine whether the former can be
      used to predict the latter. METHOD: A prospective cross sectional epidemiological
      survey of a random and representative sample of comprehensive primary schools in
      South Birmingham, UK. Participants were 389 randomly selected school children
      aged 10-11 years from 7 primary schools in South Birmingham. Their perceptions of
      dental aesthetics were determined using the Aesthetic Component (AC) of the Index
      of Orthodontic Treatment Need (IOTN). Demand for treatment was assessed by asking
      subjects if they wanted treatment with braces to correct their teeth. RESULTS:
      Only 2% of subjects assessed their dentition in the "definite need" for
      orthodontic treatment category. Demand for treatment was significantly greater in
      girls than boys (49% and 37% respectively, p < 0.05). Total demand (41%) was
      considerably greater than self assessed aesthetics in the "definite need" and
      "borderline need" categories combined (14%). Demand was accurately reflected in
      patients who perceived their dentition as having moderate to severe (AC 6-9) and
      very mild aesthetic impairment (AC 1). CONCLUSIONS: Perceptions of dental
      aesthetics using the AC of IOTN were able to predict demand for orthodontic
      treatment in patients with malocclusions of moderate to severe (AC 6-9) aesthetic
      impairment.

PMID- 22482264
TI  - What's in a name?

PMID- 22482265
TI  - Avoiding and managing the failure of conventional crowns and bridges.
AB  - The replacement of crowns and bridges is a common procedure for many dental
      practitioners. When correctly planned and executed, fixed prostheses will provide
      predictable function, aesthetics and value for money. However, when done poorly,
      they are more likely to fail prematurely and lead to irreversible damage to the
      teeth and supporting structures beneath. Sound diagnosis, assessment and
      technical skills are essential when dealing with failed or failing fixed
      restorations. These skills are essential for the 21st century dentist. This
      paper, with treated clinical examples, illustrates the areas of technical skill
      and clinical decisions needed for this type of work. It also provides advice on
      how the risk of premature failure can, in general, be further reduced. The
      article also confirms the very real risk in the UK of dento-legal problems when
      patients experience unexpected problems with their crowns and bridges. CLINICAL
      RELEVANCE: This paper outlines clinical implications of failed fixed
      prosthodontics to the dental surgeon. It also discusses factors that we can all
      use to predict and reduce the risk of premature restoration failure. Restoration
      design, clinical execution and patient factors are the most frequent reasons for
      premature problems. It is worth remembering (and informing patients) that the
      health of the underlying supporting dental tissue is often irreversibly
      compromised at the time of fixed restoration failure.

PMID- 22482266
TI  - Tooth surface loss: tools and tips for management.
AB  - Tooth surface loss is becoming increasingly prevalent. Many cases can be managed
      with preventive measures, although there remain a number of patients for whom
      restorative intervention is indicated. Traditional treatment modalities have
      entailed extensive 'full-mouth' indirect restoration, although this approach has
      a number of disadvantages. Contemporary restorative techniques allow for a
      broader range of treatment options: this paper presents an overview of common
      issues and clinical techniques to overcome these. CLINICAL RELEVANCE: Treatment
      options and guidance for managing patients who present with tooth surface loss.

PMID- 22482267
TI  - The prosthodontic pathway of the oral cancer patient.
AB  - Oral cancer patients undergo life-altering curative treatment that consists of
      surgery or a combination of surgery and radiotherapy. This can severely alter the
      functional anatomy of the oral cavity and create a challenging environment for
      successful oral rehabilitation. A multidisciplinary team approach is required to
      rehabilitate these patients successfully. It is essential to have assessment by
      an oral rehabilitation specialist before treatment, especially where primary
      rehabilitation interventions are being considered. Following cancer treatment,
      patients may suffer from a range of difficulties, from dento-facial appearance,
      to chewing, speech and swallowing. This dysfunction often leads to psychosocial
      problems, such as reduced self esteem, social contact and quality of life.
      Conventional prosthodontics has a role to play in the management of these
      patients but osseointegrated implants (OII), can be required to overcome the
      anatomical and physiological barriers. OII can be used in an environment where
      there is poor soft tissue function or little bone support, and where there is a
      dry mouth. CLINICAL RELEVANCE: This paper introduces readers to the prosthodontic
      pathway taken by some oral cancer patients. It provides an overview of current
      oral rehabilitation techniques that supplement the supportive dental care
      provided by general dental practitioners and their team after cancer treatment.

PMID- 22482268
TI  - Full-arch implant-retained prosthetics in general dental practice.
AB  - The loss of all teeth from one or both dental arches is a significant disability
      affecting self-confidence, communication, masticatory function and aesthetics.
      Whilst missing teeth cannot be restored to the natural state, the development of
      a prosthetic dentition has been a goal of dental science throughout the
      centuries. Contemporary techniques allow for the replacement of missing dentition
      with fixed or removable solutions, solving many of the problems. Implant
      dentistry has transformed this area of medicine. This article provides dental
      practitioners with an overview of this important area of patient care. CLINICAL
      RELEVANCE: Dental practitioners in clinical practice will frequently see
      edentulism; a good understanding of the available options for rehabilitation is
      essential.

PMID- 22482269
TI  - Successful removable partial dentures.
AB  - Removable partial dentures (RPDs) remain a mainstay of prosthodontic care for
      partially dentate patients. Appropriately designed, they can restore masticatory
      efficiency, improve aesthetics and speech, and help secure overall oral health.
      However, challenges remain in providing such treatments, including maintaining
      adequate plaque control, achieving adequate retention, and facilitating patient
      tolerance. The aim of this paper is to review the successful provision of RPDs.
      CLINICAL RELEVANCE: Removable partial dentures are a successful form of treatment
      for replacing missing teeth, and can be successfully provided with appropriate
      design and fabrication concepts in mind.

PMID- 22482270
TI  - Implant assessment.
AB  - Meticulous planning in implant dentistry is essential in order to achieve a
      predictable and successful outcome for both the operator and the patient. This
      paper summarizes the important aspects of planning, including factors related to
      clinical and radiographic examination and the use of study models. CLINICAL
      RELEVANCE: This paper has relevance to practitioners carrying out implant
      treatment and also to colleagues who are likely to refer patients for implants.

PMID- 22482271
TI  - Oral and dental management for head and neck cancer patients treated by
      chemotherapy and radiotherapy.
AB  - The incidence of head and neck cancer is rising. The attendant oral complications
      of cancer management make oral health maintenance a lifelong challenge for these
      patients. Holistic management in the context of a core multidisciplinary team is
      essential in optimizing outcomes. Predicting the risk of adverse oral outcomes is
      difficult. Effective communication between healthcare professionals in the core
      and extended teams and with the patient is essential. CLINICAL RELEVANCE: Primary
      care dental teams will be involved in the long-term management of oral care for
      head and cancer patients. A broad understanding of the management of head and
      neck cancer, consequences of treatment and the need for good communication is key
      to good quality patient care.

PMID- 22482272
TI  - Dental management of the elderly patient.
AB  - The dental management of the elderly individual is becoming more of an issue in
      both general dental practice and specialist prosthodontic practice. This is
      because, in general, the population is living longer and often elderly patients
      are retaining their natural teeth into their old age. In addition, there are
      often related significant medical, social and oro-dental issues that require
      consideration. CLINICAL RELEVANCE: The dental management of the elderly patient
      is an increasing problem. This paper seeks to consider the main relevant issues
      pertaining to this important subject area.

PMID- 22482273
TI  - Oral cancer: comprehending the condition, causes, controversies, control and
      consequences. 14. Mucositis.

PMID- 22482274
TI  - Technique tips--Modified butterfly deprogrammers: made easy.

PMID- 22482275
TI  - Physical signs for the general dental practitioner. CASE 92. Ringworm or tinea.

PMID- 22482276
TI  - Women's health is now core business and a global health issue.

PMID- 22482277
TI  - Cardiovascular disease in women: implications for improving health outcomes.
AB  - OBJECTIVE: To collate data on women and cardiovascular disease in Australia and
      globally to inform public health campaigns and health care interventions. DESIGN:
      Literature review. RESULTS: Women with acute coronary syndromes show consistently
      poorer outcomes than men, independent of comorbidity and management, despite less
      anatomical obstruction of coronary arteries and relatively preserved left
      ventricular function. Higher mortality and complication rates are best documented
      amongst younger women and those with ST-segment-elevation myocardial infarction.
      Sex differences in atherogenesis and cardiovascular adaptation have been
      hypothesised, but not proven. Atrial fibrillation carries a relatively greater
      risk of stroke in women than in men, and anticoagulation therapy is associated
      with higher risk of bleeding complications. The degree of risk conferred by
      single cardiovascular risk factors and combinations of risk factors may differ
      between the sexes, and marked postmenopausal changes are seen in some risk
      factors. Sociocultural factors, delays in seeking care and differences in self
      management behaviours may contribute to poorer outcomes in women. Differences in
      clinical management for women, including higher rates of misdiagnosis and less
      aggressive treatment, have been reported, but there is a lack of evidence to
      determine their effects on outcomes, especially in angina. Although enrolment of
      women in randomised clinical trials has increased since the 1970s, women remain
      underrepresented in cardiovascular clinical trials. CONCLUSIONS: Improvement in
      the prevention and management of CVD in women will require a deeper understanding
      of women's needs by the community, health care professionals, researchers and
      government.

PMID- 22482278
TI  - Stigma and stereotypes: women and sexually transmitted infections.
AB  - Sexually transmitted infections have long been associated with stigma and
      stereotypes due to their very nature. Throughout history sexually transmitted
      infections have been associated with female prostitution and deviant immoral
      behaviour making women who contract these infections particularly vulnerable to
      being stigmatised and stereotyped. Although the stigma attached to such
      infections has previously been documented in the literature, the aim of this
      research was to gain in depth insight into young Australian women's experiences
      of having a sexually transmitted infection from a feminist perspective. Findings
      from this study provide insight into the onerous effects stigma can have on women
      with these infections and sheds light on how these effects can influence self
      perceptions, fear of rejection and feelings of unworthiness. These findings can
      provide nurses with greater understanding and insight into the effects of stigma
      on women's experiences of having a sexually transmitted infection. Having this
      understanding and insight has the potential to promote therapeutic care and
      minimise the stigma that may be felt among women who have contracted this type of
      infection.

PMID- 22482279
TI  - Factors that affect acceptance of HIV microbicides among women.
AB  - Globally, women make up more than half of those infected with HIV. For women in
      nearly every region around the world, the primary mode of HIV transmission is
      through heterosexual sex. However, over thirty years into the HIV/AIDS epidemic
      women still lack sufficient means of protecting themselves against HIV. Vaginal
      HIV microbicides (VHMs) are a promising new method to prevent HIV infection. VHMs
      are chemical substances that can destroy HIV, block its entry into or fusion with
      the target cell or inhibit HIV replication once the virus has entered a target
      cell. They can be applied through various delivery methods intravaginally. VHMs
      are designed to be used by women and to that end it is crucial to understand
      women's preferences for formulation, use and other characteristics in order to
      determine how to increase adherence and acceptability. Of particular
      consideration is how relationship dynamics will affect microbicide usage. The
      purpose of this review is to examine the most recent body of literature regarding
      male and female perceptions of VHMs to prevent male to female transmission of HIV
      in order to gain a greater understanding of the factors that affect adherence and
      acceptability of VHM usage among women. A greater understanding of the factors
      that affect adherence and acceptance of VHMs will have an impact on the uptake of
      VHMs, allow nurses and other health care providers to counsel clients more
      effectively about their use and point to new directions needed on the research
      and development of future microbicides.

PMID- 22482280
TI  - Women and cardiovascular disease: at a social disadvantage?
AB  - BACKGROUND: Cardiovascular disease is the most common cause of death in
      Australian women. The genesis and progression of cardiovascular disease is
      modulated by a complex interplay of genetic, physiological, social and economic
      circumstances. Increasingly the impact of racial, ethic, social and economic
      inequalities is identified as predictors of cardiovascular disease outcome.
      Despite important advances over the last 30 years in reducing age adjusted
      mortality from cardiovascular disease, it continues to represent a major social
      and economic burden nationally and internationally. AIM: This paper provides a
      critical review of the social issues impacting upon women in Australia. It also
      identifies areas for future interventions with a view to improving outcomes in
      women with cardiovascular disease. METHOD: The bibliographic databases; CINAHL,
      MEDLINE, PsycARTICLES, were searched for relevant studies using the search terms
      'women', 'cardiovascular disease', and 'socio-economic status'. FINDINGS: While
      some gains have been made in reducing the risk factor profile and rates of death
      from cardiovascular disease, it is clear that gender, race and socioeconomic
      disparities persist. CONCLUSIONS: New approaches are required to improve health
      differentials for CVD, and reduce the impact of gender, racial, ethic, social and
      economic factors on health disparities.

PMID- 22482281
TI  - Autobiography as genre for qualitative data: a reservoir of experience for
      nursing research.
AB  - This paper is concerned with the use of published literary autobiographies that
      contain first-hand accounts of illness narratives, to explore their usefulness as
      a form of qualitative data to generate knowledge that can inform nursing
      practice. There is increasing realisation that the experiences of patients and
      families should be used to guide health care service delivery, and
      autobiographical accounts are a valuable resource, providing first-hand accounts
      of the ways illness, disability, and health care, are experienced by patients and
      their families.

PMID- 22482282
TI  - Issues and challenges in implementing cervical cancer screenings in the emergence
      of HPV vaccination in Thailand.
AB  - The discovery of the HPV vaccine has been a major breakthrough in preventing
      cervical cancer and other HPV-related diseases around the globe. Cervical cancer
      is a significant public health problem in Thailand. Despite the long-time
      availability of cervical cancer screening programs in Thailand, the uptake among
      the target female population remains low. HPV vaccines were approved by the Food
      and Drug Administration of Thailand in 2007. As of March 2011, due to financial
      limitations, HPV vaccines have still not been included in the national
      immunization program under the public health benefit plans although individuals
      has the option to pay privately for the vaccine. This paper discusses the issues
      and challenges in implementing cervical cancer screening programs in the era of
      HPV vaccination in Thailand. Recommendations to increase the uptake of cervical
      cancer screening and further research to inform a policy regarding the cervical
      cancer screening measures are proposed.

PMID- 22482283
TI  - Cultural challenges to secondary prevention: implications for Saudi women.
AB  - Like other highly developed countries, cardiovascular disease (CVD) and coronary
      heart disease (CHD) are major health problems in Saudi Arabia. The aetiology of
      cardiovascular disease (CVD) burden within the Saudi population is similar to
      Western countries with atherosclerosis, hypertension, ischemic heart disease and
      diabetes highly prevalent with the main risk factors being smoking, obesity and
      inactivity. There are differences between Saudi men and women in epidemiology,
      risk factors and health service provision for CHD. These sex and gender based
      factors are important in considering the health and well-being of Saudi women.
      Currently, there is Limited focus on the cardiovascular health of Saudi women.
      The aim of this paper is to examine culturally specific issues for Saudi women
      and the implications for secondary prevention.

PMID- 22482284
TI  - Migration of women from the Philippines: implications for healthcare delivery.
AB  - Filipinos have been an important part of the global workforce since the first
      half of the twentieth century. The initial migration of primarily men has shifted
      to an increasing numbers of women in recent decades. These changes are primarily
      attributed to a high demand for domestic workers, nurses and occupations that are
      female dominated. In 2005, about 70% of the international Labour migrants are
      women from the Philippines. Living in a foreign land, these women face challenges
      that affect their physical, emotional and social well being. Especially on their
      first year living abroad, these women experience significant stress which affects
      their health as they adjust to a new work environment, culture, social norms,
      diet, and weather. The emotional strain can be greater for those who have left
      their families behind in the Philippines and aggravated by the financial need to
      send money to them. Striking examples, such as the homicide rate of Filipino
      women married to Australian men being 5.6 times higher than that of Australian
      born women, underscores the importance of supportive health care environments and
      appreciating socio-cultural factors. In the delivery of healthcare services to
      migrant women, it is critical to consider the unique socio-cultural background of
      women as well as health beliefs and practices.

PMID- 22482285
TI  - The effects of manganese precursors on Mn-based/TiO2 catalysts for catalytic
      reduction of NO with NH3.
AB  - Manganese acetate (MnAc) and manganese nitrate (MnN) were employed as precursors
      for the preparation of MnAc)/TiO2, Mn (N)/TiO2, Mn(Ac)-Ce/TiO2, and Mn(N)-Ce/TiO2
      by impregnation. These complexes were used as catalysts in the low-temperature
      selective catalytic reduction of NO with NH3. The influence of manganese
      precursors on catalyst characteristics, the reduction activity, and the stability
      of the catalysts to poisoning by H2O and SO2 were studied. Experiments showed
      that Mn(N) produced MnO2 with large grain sizes in Mn(N)/TiO2 catalyst. On the
      contrary, Mn(Ac) led to highly dispersed and amorphous Mn2O3 in Mn (Ac)/TiO2
      catalyst, which had better catalytic activity and stability to SO2 at low
      temperatures. The doping of cerium reduced the differences in catalytic
      performance between the catalysts derived from different Mn precursors.

PMID- 22482286
TI  - Effect of biocover equipped with a novel passive air diffusion system on
      microbial methane oxidation and community of methanotrophs.
AB  - A novel biocover with passive air diffusion system (PADS) was designed in this
      study. Its effect on landfill gas components in the macrocosms of simulated
      biocover systems was also investigated. The results show that O2 concentration
      increased in the whole profile of the macrocosms equipped with PADS. When
      simulated landfill gas (SLFG) flow rate was no more than 40 mL min(-1), the
      methane oxidation rate was 100%. The highest CH4 oxidation capacity reached to
      31.34 mol m(-3) day(-1). Molecular microbiology analysis of the soil samples
      taken from the above macrocosm showed that the growth of type I methanotrophs was
      enhanced, attributable to enhanced air diffusion and distribution, whereas the
      microbial diversity and population density of type II methanotrophs were not so
      affected, as evidenced by the absence of any difference between the biocover
      equipped with PADS and that of the control. According to a phylogenic analysis,
      Methylobacter Methylosarcinafor type I, and Methylocystis, Methylosinus for type
      II, were the most prevalent species in the macrocosm with PADS.

PMID- 22482287
TI  - Quantification of emission factor uncertainty.
AB  - Emissions factors are important for estimating and characterizing emissions from
      sources of air pollution. There is no quantitative indication of uncertainty for
      these emission factors, most factors do not have an adequate data set to compute
      uncertainty, and it is very difficult to locate the data for those that do. The
      objectives are to compare the current emission factors of Electric Generating
      Unit NOx sources with currently available continuous emission monitoring data,
      develop quantitative uncertainty indicators for the Environmental Protection
      Agency (EPA) data quality rated emission factors, and determine the possible
      ranges of uncertainty associated with EPA's data quality rating of emission
      factors. EPA's data letter rating represents a general indication of the
      robustness of the emission factor and is assigned based on the estimated
      reliability of the tests used to develop the factor and on the quantity and
      representativeness of the data. Different sources and pollutants that have the
      same robustness in the measured emission factor and in the representativeness of
      the measured values are assumed to have a similar quantifiable uncertainty. For
      the purposes of comparison, we assume that the emission factor estimates from
      source categories with the same letter rating have enough robustness and
      consistency that we can quantify the uncertainty of these common emission factors
      based on the qualitative indication of data quality which is known for almost all
      factors. The results showed that EPA's current emission factor values for NOx
      emissions from combustion sources were found to be reasonably representative for
      some sources; however AP-42 values should be updated for over half of the sources
      to reflect current data. The quantified uncertainty ranges were found to be 25
      62% for A rated emission factors, 45-75% for B rated emission factors, 60-82% for
      C rated emission factors, and 69-86% for D rated emission factors, and 82-92% for
      E rated emission factors.

PMID- 22482288
TI  - Benefits of clean development mechanism application on the life cycle assessment
      perspective: a case study in the palm oil industry.
AB  - This study performed an assessment on the beneficial of the Clean Development
      Mechanism (CDM) application on waste treatment system in a local palm oil
      industry in Malaysia. Life cycle assessment (LCA) was conducted to assess the
      environmental impacts of the greenhouse gas (GHG) reduction from the CDM
      application. Calculations on the emission reduction used the methodology based on
      AM002 (Avoided Wastewater and On-site Energy Use Emissions in the Industrial
      Sector) Version 4 published by United Nations Framework Convention on Climate
      Change (UNFCC). The results from the studies showed that the introduction of CDM
      in the palm oil mill through conversion of the captured biogas from palm oil mill
      effluent (POME) treatment into power generation were able to reduce approximate
      0.12 tonnes CO2 equivalent concentration (tCO2e) emission and 30 kW x hr power
      generation per 1 tonne of fresh fruit bunch processed. Thus, the application of
      CDM methodology on palm oil mill wastewater treatment was able to reduce up to
      1/4 of the overall environment impact generated in palm oil mill.

PMID- 22482289
TI  - Black carbon particulate matter emission factors for buoyancy-driven associated
      gas flares.
AB  - Flaring is a technique used extensively in the oil and gas industry to burn
      unwanted flammable gases. Oxidation of the gas can preclude emissions of methane
      (a potent greenhouse gas); however, flaring creates other pollutant emissions
      such as particulate matter (PM) in the form of soot or black carbon (BC).
      Currently available PM emissionfactors for flares were reviewed and found to be
      questionably accurate, or based on measurements not directly relevant to open
      atmosphere flares. In addition, most previous studies of soot emissions from
      turbulent diffusion flames considered alkene or alkyne based gaseous fuels, and
      few considered mixed fuels in detail and/or lower sooting propensity fuels such
      as methane, which is the predominant constituent of gas flared in the upstream
      oil and gas industry. Quantitative emission measurements were performed on
      laboratory-scale flares for a range of burner diameters, exit velocities, and
      fuel compositions. Drawing from established standards, a sampling protocol was
      developed that employed both gravimetric analysis of filter samples and real-time
      measurements of soot volume fraction using a laser-induced incandescence (LII)
      system. For the full range of conditions tested (burner inner diameter [ID] of
      12.7-76.2 mm, exit velocity 0.1-2.2 m/sec, 4- and 6-component methane-based fuel
      mixtures representative of associated gas in the upstream oil industry), measured
      soot emission factors were less than 0.84 kg soot/10(3) m3 fuel. A simple
      empirical relationship is presented to estimate the PM emission factor as a
      function of the fuel heating value for a range of conditions, which, although
      still limited, is an improvement over currently available emission factors.

PMID- 22482290
TI  - Field evaluation of particulate matter measurements using tapered element
      oscillating microbalance in a layer house.
AB  - The tapered element oscillating microbalance (TEOM) is one type of continuous
      ambient particulate matter (PM) monitor. Adsorption and desorption of moisture
      and semivolatile species may cause positive or negative artifacts in TEOM PM mass
      measurement. The objective of this field study was to investigate possible
      uncertainties associated with TEOM measurements in the poultry operation
      environment. For comparisons of TEOM with filter-based gravimetric method, four
      instruments (TEOM-PM10, low-volume PM10 sampler TEOM-PM2.5, and PM2.5 speciation
      sampler) were collocated and tested inside a poultry house for PM2.5 and PM10 (PM
      with aerodynamic equivalent diameter < or =2.5 and < or =10 microm, respectively)
      measurements. Fifteen sets of 24-hr PM10 concentrations and 13 sets of 24-hr
      PM2.5 measurements were obtained. Results indicate that compared with filter
      based gravimetric method, TEOM gave significantly lower values of both PM10 and
      PM2.5 mass concentrations. For PM10, the average ratio of TEOM to the gravimetric
      method was 0.936. For PM2.5, the average ratio of TEOM to the gravimetric method
      was 0.738. Particulate matter in the poultry houses possibly contains
      semivolatile compounds and moisture due to high levels of relative humidity (RH)
      and gas pollutants. The internal heating mechanism of the TEOM may cause losses
      in mass through volatilization. To investigate the effects of TEOM settings on
      concentration measurements, the heaters of two identical TEOMs were set at 50
      degrees C, 30 degrees C, or no heating at all. They were collocated and tested
      for total suspended particle (TSP), PM10, and PM25 measurements in layer house
      for 6 weeks. For all TSR PM10, and PM2.5 measurements, the internal TEOM
      temperature setting had a significant effect (P < 0.05). Significantly higher PM
      mass concentrations were measured at lower temperature settings. The effects of
      environmental (i.e., temperature, RH, NH3 and CO2 concentrations) and
      instrumental (i.e., filter loading and noise) parameters on PM measurements were
      also assessed using regression analysis.

PMID- 22482291
TI  - Simulating industrial emissions using atmospheric dispersion modeling system:
      model performance and source emission factors.
AB  - In this paper, the Gaussian Atmospheric Dispersion Modeling System (ADMS4) was
      coupled with field observations of surface meteorology and concentrations of
      several air quality indicators (nitrogen oxides (NOx), carbon monoxide (CO), fine
      particulate matter (PM10) and sulfur dioxide (SO2)) to test the applicability of
      source emission factors set by the European Environment Agency (EEA) and the
      United States Environmental Protection Agency (USEPA) at an industrial complex.
      Best emission factors and data groupings based on receptor location, type of
      terrain and wind speed, were relied upon to examine model performance using
      statistical analyses of simulated and observed data. The model performance was
      deemed satisfactory for several scenarios when receptors were located at downwind
      sites with index of agreement 'd' values reaching 0.58, fractional bias 'FB' and
      geometric mean bias 'MG' values approaching 0 and 1, respectively, and normalized
      mean square error 'NMSE' values as low as 2.17. However, median ratios of
      predicted to observed concentrations 'Cp/Co' at variable downstream distances
      were 0.01, 0.36, 0.76 and 0.19 for NOx, CO, PM10 and SO2, respectively, and the
      fraction of predictions within a factor of two of observations 'FAC2' values were
      lower than 0.5, indicating that the model could not adequately replicate all
      observed variations in emittant concentrations. Also, the model was found to be
      significantly sensitive to the input emission factor bringing into light the
      deficiency in regulatory compliance modeling which often uses internationally
      reported emission factors without testing their applicability.

PMID- 22482292
TI  - Particulate matter emission rates from beef cattle feedlots in Kansas-reverse
      dispersion modeling.
AB  - Open beef cattle feedlots emit various air pollutants, including particulate
      matter (PM) with equivalent aerodynamic diameter of 10 microm or less (PM10);
      however limited research has quantified PM10 emission rates from feedlots. This
      research was conducted to determine emission rates of PM10 from large cattle
      feedlots in Kansas. Concentrations of PM10 at the downwind and upwind edges of
      two large cattle feedlots (KS1 and KS2) in Kansas were measured with tapered
      element oscillating microbalance (TEOM) PM10 monitors from January 2007 to
      December 2008. Weather conditions at the feedlots were also monitored. From
      measured PM10 concentrations and weather conditions, PM10 emission rates were
      determined using reverse modeling with the American Meteorological Society/U.S.
      Environmental Protection Agency Regulatory Model (AERMOD). The two feedlots
      differed significantly in median PM10 emission flux (1.60 g/m2-day for KS1 vs.
      1.10 g/m2-day for KS2) but not in PM10 emission factor (27 kg/1000 head-day for
      KS1 and 30 kg/1000 head-day KS2). These emission factors were smaller than
      published U.S. Environmental Protection Agency (EPA) emission factor for cattle
      feedlots.

PMID- 22482293
TI  - Improving the activity of Mn/TiO2 catalysts through control of the pH and valence
      state of Mn during their preparation.
AB  - In this study, the authors investigated the influence of the valence state of Mn
      on the efficacy of selective catalytic reduction using a Mn-based catalyst. The
      nitrogen oxides (NOx) conversion rate of the catalyst was found to be dependent
      on the type of TiO2 support employed and on the temperature, as the catalyst
      showed an excellent conversion of > 80% at a space velocity of 60,000 hr(-1) when
      the temperature was above 200 degrees C. Brunauer-Emmett-Teller, X-ray
      diffraction, and X-ray photoelectron spectroscopy analyses confirmed that
      catalyst displaying the highest activity contained the Mn4+ species and that its
      valence state was highly dependent on the pH during the catalyst preparation.

PMID- 22482294
TI  - OSHA: a short primer for health care employers.

PMID- 22482295
TI  - 23rd TNAI Biennial National Conference, Kochi, 25-26 November 2010. Presidential
      address by the outgoing president.

PMID- 22482296
TI  - Unfolding the conference theme: planning and implementing change in nursing.

PMID- 22482297
TI  - Job satisfaction of nursing faculty in Bangalore.

PMID- 22482298
TI  - Infection control among health care assistants.

PMID- 22482299
TI  - Occurence and predictors of microalbuminuria among patients with type II diabetes
      mellitus.

PMID- 22482300
TI  - Television viewing and health behaviour of children in south India.

PMID- 22482301
TI  - Role of nurse in invitro fertilization.

PMID- 22482302
TI  - World Health Day: 7 April 2011. Theme: Antimicrobial resistance: no action today,
      no cure tomorrow.

PMID- 22482303
TI  - Structured teaching programme for women undergoing abdominal hysterectomy.

PMID- 22482304
TI  - Nursing education: opportunities and challenges.

PMID- 22482305
TI  - Speech by her Excellency, the President of India, Shrimati Pratibha Devisingh
      Patil at the presentation of the National Florence Nightingale Awards for nursing
      personnel.

PMID- 22482306
TI  - Presidential address and unfolding the theme--closing the gap: increasing access
      and equity.

PMID- 22482307
TI  - Nursing audit.

PMID- 22482308
TI  - Ambulatory care.

PMID- 22482309
TI  - Patient involvement in clinical governance.

PMID- 22482310
TI  - Effect of meditation on well-being of nursing students.

PMID- 22482311
TI  - Stage IV breast cancer--does local surgery improve outcome?

PMID- 22482312
TI  - Stress urinary incontinence--often underdiagnosed and under-reported.

PMID- 22482313
TI  - A study of twins--in search of an optimal age for delivery.
AB  - The question regarding the optimal age of delivery in twins remains unanswered. A
      prospective observational study was carried out in the gynaecology and obstetrics
      department of RG Kar Medical College and Hospital, Kolkata during 2008-2009 to
      arrive at a logical conclusion to this question. The objective of this study was
      to evaluate the optimal timing of delivery in twins and compare the perinatal
      outcome in these babies by dividing them into 3 groups: 34 weeks to 35 weeks 6
      days, 36 weeks to 37 weeks 6 days and >38 weeks. Perinatal outcome was also
      compared between different modes of delivery. Few maternal complications like pre
      eclampsia, anaemia, premature rupture of membrane, preterm labour and antepartum
      haemorrhage were also evaluated.

PMID- 22482314
TI  - Ocular effects of long term use of topical steroids among children and
      adolescents with vernal keratoconjunctivitis: a prospective observational study.
AB  - Topical steroids were often irrationally used on long term basis for quick relief
      from ocular discomfort of inflammatory eye conditions like vernal
      keratoconjunctivitis in spite of their well known deleterious ocular effects. The
      present study was undertaken to determine the ocular effects of long term use of
      topical steroids among the patients with vernal keratoconjunctivitis and also to
      evaluate the ocular responses after withdrawal of steroids. The prospective
      observational study was carried out in a tertiary eye care centre of West Bengal.
      A total 150 referred patients of vernal keratoconjunctivitis, those used topical
      steroids for more than a month were included in the study. A complete set of
      ophthalmic examinations including measurement of intra-ocular pressure and visual
      acuity was carried out during registration. After withdrawal of steroids, the
      patients were followed-up periodically and finally evaluated after 8 weeks for
      any Improvement of Intra-ocular pressure and best corrected visual acuity. The
      data was analysed by SPSS 12.0.1 software package. Proportions were used for
      Interpretation. Paired t-test was used for comparison between two proportions
      (before and after withdrawal of steroids) and p-value <0.05 was considered as the
      level of significance. Though ropy mucus discharge with minimal conjunctival
      involvement was found the most common (74.7%) ocular manifestation, grave
      consequences like glaucoma was also evident among 8.7% of the study participants.
      Significant improvements (p<0.05) were observed for both reduction of intra
      ocular pressure and visual acuity after 8 weeks of withdrawal of topical
      steroids. Topical steroids should be used cautiously with periodic ophthalmic
      examinations including intra-ocular pressure.

PMID- 22482315
TI  - Emergency management of sigmoid volvulus--institutional experience over four
      years.
AB  - Sigmoid volvulus is a serious surgical emergency and a common cause of large
      bowel obstruction in India. Patients present with abdominal pain, distension and
      obstipation and abdominal skiagram usually reveals the characteristic omega sign.
      Non-operative detorsion with early elective sigmoidectomy is the procedure of
      choice where gut viability is not in doubt and features of peritonitis are
      absent. The objective of this study was to demonstrate the most suitable
      procedure for management of patients with sigmoid volvulus needing emergency
      surgery. Results revealed a high incidence of burst abdomen and anastomotic leak
      as well as a high mortality rate in patients undergoing resection with primary
      anastomosis without proximal colostomy. Mortality was least with Hartmann's
      procedure although there was a higher incidence of wound infection. Thus, in the
      hospital setting, we consider Hartmann's procedure to be the best emergency
      surgical procedure for sigmoid volvulus as it limits mortality to the least.

PMID- 22482316
TI  - Stress urinary incontinence and quality of life in women.

PMID- 22482317
TI  - Stress urinary incontinence--an overview.

PMID- 22482318
TI  - Time trends in ectopic pregnancy over a decade--a retrospective hospital-based
      study.
AB  - A 10-year study to evaluate the time trends of ectopic pregnancy showed a gradual
      but steady rise of incidence from 1/179 to 1/108. Reproductive failure
      constituted the major bulk but contraceptive failure is gradually increasing.
      Interestingly failure of emergency contraception has emerged as another risk
      factor in recent years. Laparotomy is still the major modality of treatment with
      medical management possible in only 3.1% of cases. Laparoscopic management has
      been adopted from 2003 and only 20.2% of cases were managed by laparoscopy in
      2006, which is much lower than that of our western counterparts.

PMID- 22482319
TI  - Diagnostic yield of broncho-alveolar lavage fluid and postbronchoscopic sputum
      cytology in endoscopically non-visible lung cancers.
AB  - Diagnostic yield of broncho-alveolar lavage (BAL) fluid and postbronchoscopic
      sputum (PBS) cytology is very high in endoscopically visible bronchogenic
      carcinoma, but they are also helpful in diagnosis of those lung cancers which are
      not visible bronchoscopically. Objective of this prospective study is to analyse
      the diagnostic yield of BAL fluid and PBS cytology in endoscopically non-visible
      lung cancer. Thirty patients with chest radiographic abnormality suspicious of
      lung cancer without endobronchial abnormality underwent BAL fluid and PBS
      cytology examination in the department of respiratory medicine of Calcutta
      National Medical College and Hospital over 1 year and 3 months. The final
      diagnosis was bronchogenic carcinoma in 21, tuberculoma/tuberculosis in 5,
      bacterial pneumonia in 3 and encysted empyema in 1. Among the 21 patients with
      bronchogenic carcinoma, BAL was positive for malignant cell in 13 patients (62%).
      The diagnostic yield of the BAL was influenced by size, location, radiographic
      pattern and cell type of the tumour. PBS cytology was positive in 3 patients
      (14%) only, all of which were positive with BAL fluid also. BAL fluid cytology
      proved to be a valuable diagnostic tool in diagnosis of endoscopically non
      visible lung cancer. Size, location, radiographic pattern and cytological type of
      the lesions were important determinants of the diagnostic yield. PBS cytology
      provided no additional benefit.

PMID- 22482320
TI  - Prehypertension and associated factors among medical students of SSIMS & RC,
      Davangere--a cross-sectional study.
AB  - Hypertension is a chronic condition of concern and a major public health problem
      posing a challenge to population in socioeconomic and demographic transition.
      Prehypertension in adolescents and young adults is an important risk for
      developing hypertension in later years of life. Therefore this study was taken up
      among medicos of this institute to study about prehypertension and its associated
      factors. The objective of the study was to see the prevalence of prehypertension
      and its associated factors among medicos of SSIMS&RC, Devangere. The study
      duration was from 1st July 2009 to 31st August 2009. The sample size worked out
      to be 100 and this set of participants was selected by systematic random
      sampling. A predesigned and pretested proforma was used to collect the relevant
      data. Blood pressure (BP) was measured in sitting posture using a standard
      sphygmomanometer on two different occasions and the average was noted. BP was
      classified as per the Joint National Committee on prevention, detection,
      evaluation and treatment of blood pressure. Data was analysed by SPSS.
      Descriptive statistics was presented by, percentage, mean and SD. Groups are
      compared with the help of z-test, t-test and Chi-square test. All the
      participants were in the age group of 18 to 22 years and mean age was 20.29 +/-
      0.86 years. Among 100 participants 56 were males and 44 were females. The mean
      systolic blood pressure was 117.68 +/- 7.16 mm Hg and that of diastolic blood
      pressure was 77.3 +/- 7.93 min Hg. The percentage of prehypertension and
      hypertension was 67%. Three participants were diagnosed to be hypertensive.

PMID- 22482321
TI  - Leptospirosis: an institutional experience.
AB  - Leptospirosis, a common zoonotic disease, may present with variable clinical
      manifestations in between two extremes. Possibility must be excluded in any
      febrile patient with hepatorenal derangement. There are different reports
      regarding prevalence pattern, presentations and case fatality rate from different
      parts of the country. The purpose of this study was to find out the mode of
      presentation, biochemical profile and complications of leptospirosis cases in an
      apical level and make a comparison of same with other parts of India. Fifty-one
      consecutive cases of leptospirosis were selected for this study. Thorough
      clinical examination was done. ELISA test was done in the second week of illness.
      Haemogram, liver and renal function tests, coagulation profile, creatine
      phosphokinase (CPK), chest xray, ECG were done in all patients. Presenting
      features were fever (100%), myalgia (78.4%), headache (41.2%), jaundice (17.6%),
      oliguria (29.4%), respiratory distress (25.5%), bleeding manifestations (9.8%),
      altered sensorium (21.6%). Icterus was found in 74.5% of patients,
      hepatosplenomegaly in 72.5%, tachypnoea in 52.9%, bleeding manifestations in
      35.3%, encephalopathy in 21.6%, hypotension in 15.7% and meningeal signs in 5.9%
      cases. Case fatality rate was 7.8%. From the study, it becomes evident that
      though severe leptospirosis has declined, mild leptospirosis has Increased. The
      reasons for decline of severe leptospirosis may be greater awareness,
      availability of better diagnostic tool along with widespread use of antibiotics.
      So, high index of suspicion may eventually reduce complications. It would be wise
      to start appropriate antibiotics empirically in suspected cases of leptospirosis.

PMID- 22482322
TI  - Intra-operative floppy iris syndrome.
AB  - Intra-operative floppy iris syndrome (IFIS) is a recently described phenomenon
      seen in patients undergoing cataract surgery who have taken tamsulosin, an alpha
      1a-adrenergic antagonist used for benign prostatic enlargement. Incidence of even
      90% has been reported in studies with majority of them being severe in nature.
      Prevention of intra-operative floppy iris syndrome by withdrawing tamsulosin pre
      operatively has not shown consistent result. The risk of dangers of intra
      operative floppy iris syndrome may be decreased by using preoperative atropine or
      by using visco-adaptive devices, intra-operatively.

PMID- 22482323
TI  - Can IMA-RNTCP stop TB by 2050?
AB  - Tuberculosis has been with mankind since time immemorial. No other disease has so
      much sociological, economic and health significance as tuberculosis. In the
      poorly functioning tuberculosis control programme, the ratio of incidence to
      prevalence may be as high as 1: 3.5. Experience and observations from both
      developed and developing countries have demonstrated that if case detection and
      cure rates in smear positive cases are consistently achieved to 70 % and 85 %
      respectively, the incidence would decline to 5% annually while prevalence decline
      very rapidly, being reduced to less than half of its previous level within three
      years. Since RNTCP India is based on scientific principles of DOTS strategy, its
      effective clinical and public health management, committed and co-ordinated
      efforts of public and private partners (IMA) would certainly lead to decline the
      prevalence (already declined from 586/1,00,000 in 1990 to 185/1,00,000 population
      in 2008 - 68 % reduction), mortality rate from 42/ 1,00,000 in 1990 to
      21/1,00,000 in 2015 (already reduced to 24/1,00,000 in 2008 - 43 % reduction) as
      target set under indicator 23 of TB-related Millennium Development Goal. This
      kind of impact would result in halting and reversing TB Incidence to pave way for
      future effective control of TB, which may not remain a public health problem by
      2050. Thus, TB control is a winnable battle.

PMID- 22482324
TI  - Invasive carcinoma of cervix during pregnancy--a case report and review of
      literature.
AB  - Carcinoma of cervix is the commonest malignancy seen in Indian women in all age
      groups and therefore commonly seen in pregnancy. However, most of the cases
      remain in early stage and the occurrence of invasive cervical carcinoma is
      relatively uncommon in pregnant women. There is always a therapeutic dilemma
      faced by the gynaecologic oncologist and the maternal foetal specialist regarding
      management of pregnancy with cervical malignancy. A 30 years old, multiparous
      woman diagnosed to have squamous cell carcinoma of the cervix FIGO stage IB1 in
      the early second trimester was treated by radical hysterectomy followed by
      radiotherapy is being reported. The various therapeutic options and prognosis are
      discussed.

PMID- 22482325
TI  - Chronic portal vein thrombosis due to combined deficiency of protein C and
      protein S.
AB  - Portal vein thrombosis (PVT) is a rare disorder that is associated with a variety
      of underlying condition of which liver cirrhosis, malignancy and
      myeloproliferative disorders are the most common. It is of two types, acute and
      chronic portal vein thrombosis. Anticoagulation therapy is recommended for all
      patients with acute portal vein thrombosis. Chronic portal vein thrombosis is
      characterised by the development o f portal hypertension. Bleeding from ruptured
      varices is the main complication. In the absence of bleeding, continuous
      anticoagulation therapy should be considered for chronic portal vein thrombosis
      in whom an underlying prothrombotic factor is to be identified. Here in this
      report a 13-year-old girl presented with haematemesis. The spleen was hugely
      enlarged. Her Hb was 8.38 g/dl. Grade III oesophageal varices were found in
      oesophagogastroduodenostomy. CT abdomen showed portal cavernoma formation with
      increased splenic collateral. Protein C activity was 45% and protein S activity
      was 40%. She was treated with beta-blocker, endoscopic variceal ligation followed
      by low molecular weight heparin and warfarin.

PMID- 22482326
TI  - Non-Hodgkin's lymphoma of the hard palate.
AB  - Non-Hodgkin's lymphoma usually involves lymph nodes, but can involve extranodal
      sites. Oral lymphomas are relatively rare and often difficult to diagnose in a
      clinical setting. A case of non-Hodgkin's lymphoma of the hard palate who had
      undergone external beam radiation therapy and was found to be well one year
      following treatment is reported.

PMID- 22482327
TI  - A rare case of persistent muellerian duct syndrome presenting as inguinal hernia.
AB  - Irreducible inguinal hernia is a very common emergency surgical problem. In most
      of the cases the content is either bowel or omentum. Testis, as a content of
      hernial sac is also found in undescended testis presenting as obstructed or
      irreducible congenital inguinal hernia. Here a case is reported of a
      phenotypically normal looking male presenting with irreducible left sided
      inguinal hernia which on exploration revealed uterus, fallopian tubes and testis.
      The case is presented because of its rarity of presentation.

PMID- 22482328
TI  - Photodynamic therapy for circumscribed choroidal haemangioma: a case report.
AB  - Choroidal haemangioma is a benign tumour with visual acuity diminution due to
      subretinal fluid accumulation. There are many modalities of treatment of this
      visually disabling syndrome, some of them being argon laser photocoagulation,
      cryotherapy, external beam irradiation, proton beam radiotherapy, episcleral
      plaque radiotherapy and transpupillary thermotherapy. Another new modality of
      treatment with remarkable success rate is photodynamic therapy. In this modality
      a photosensitiser is injected intravenously followed by irradiation of a specific
      wave length for a specified time period. The photosensitiser concentrates within
      the vascular channels and after irradiation these channels are irreversibly
      obliterated. A 62 years old female patient of choroidal haemangioma, who
      presented in eye outpatient department was treated with the standard protocol
      used for photodynamic therapy. On follow-up of this patient it was found that
      there was improvement in the visual acuity from 6/12 in the left eye (affected
      eye) to 6/9. Not only was there an improvement in the visual acuity but there was
      anatomical improvement too as was evident by regressed cystoid macular oedema and
      circumscribed choroidal haemangioma. After six months of follow-up there was no
      leakage of dye with digital fluorescein angiography and indocyanine green.

PMID- 22482329
TI  - Primary schwannoma of adrenal gland: a case report.
AB  - Primary schwannoma of the adrenal gland is a rare tumour and only one case is
      described in Indian literature. We report the clinical, pathological and
      radiological features of adrenal schwannoma discovered accidentally in a 34 years
      old female as part of gynaecology work-up.

PMID- 22482330
TI  - Undiagnosed case of term heterotopic pregnancy with ectopic abdominal pregnancy.
AB  - Heterotopic pregnancy involves coexisting intra-uterine and extra-uterine
      gestations. The incidence for natural uninduced pregnancy is 1 in 30,000
      pregnancies. However the incidence is increasing with ovulation induction and
      artificial reproductive techniques. In more than 90% heterotopic pregnancies, the
      ectopic implantation is in the fallopian tube. A case of undiagnosed term
      heterotopic pregnancy in a 26-year-old primigravida is reported. She was referred
      from a practising obstetrician as a case of term twin pregnancy. Her regular
      antenatal records suggested intra-uterine growth restriction in one foetus of the
      twin. After confirmation of findings with ultrasound she was taken for emergency
      caesarean section. Heterotopic pregnancy was diagnosed on opening the abdomen.
      The term abdominal pregnancy was managed successfully. Although remained
      undiagnosed till term, good maternal and perinatal outcome was noted with
      survival of both the babies.

PMID- 22482331
TI  - Hepatitis B and pregnancy: challenges in India.
AB  - Hepatitis B is a global public health problem, with the highest number of
      hepatitis B virus (HBV) positive cases in China and India and being asymptomatic,
      the disease burden under appreciated. It is a unique challenge to manage HBV
      infection in pregnant women, with consequences to both mother and newborn. About
      12 studies in the Indian subcontinent have looked specifically at the prevalence
      of hepatitis B surface antigen (HBsAg) positivity in the pregnant women. The
      prevalence rate of HBsAg positivity in pregnant women varies from 1-9% in
      different parts of the country. The government/Ministry of Health and family
      Welfare/health institutes in India need to develop a mandate policy for the
      prevention of perinatal transmission of HBV infection, to minimise the risk for
      perinatal HBV transmission, and for the management of HBV during and after
      pregnancy. A step forward can be taken by implementing universal childhood
      hepatitis B immunisation (adopted by more than 160 countries) in National
      Immunisation programme to reduce HBV carrier rate and thereby the incidence of
      long-term consequences like cirrhosis and liver cancer.

PMID- 22482332
TI  - National Society Cardiovascular Journals of Europe: Almanac 2011.

PMID- 22482333
TI  - Study of formulation of pharmaceutical solution form of paracetamol in the
      pediatric clinical practice.
AB  - AIM of the study was selection of 2 different formulations of paracetamol of 2.5%
      (125 mg/5 mL) in the Pediatric practice. Paracetamol is widely used in the form
      of the syrup, with usual percentage of acting ingredient of 125 mg/5 mL. MATERIAL
      AND METHODS: Both samples of the paracetamol syrup were monitored each day
      regarding organoleptic features (potential changes in color, smell, transparency,
      crystallization, etc.), whilst in monthly intervals (1 month, 2 months, 3 months,
      4 months and 5 months) content of the paracetamol was analyzed, with the
      spectrophotometric method (HPLC). RESULTS AND DISCUSSION: Content of the
      paracetamol in both syrup formulations has not incurred any change even after a
      period of 6 months of storage, which showed that these two formulations are
      appropriate ones. From six different formulations of the paracetamol syrup in
      percentage of 2.5% (125 mg/5 ml) as more appropriate are: fifth formulation which
      can be considered, without no doubt, as most appropriate one because of its
      relatively low cost, an stabilized pH, a quite likeable taste and as such also
      consequently acceptable in the pediatric practice. In some cases, mainly during
      the winter, the crystallization of the paracetamol in the lid, walls and bottom
      of the bottle was ascertained also. CONCLUSION: Syrup of paracetamol 2.5% (125
      mg/5 mL) as per the formulation 5 experimented by our side can be recommended as
      most appropriate to be produced in industrial conditions for purposes of
      pediatric practice.

PMID- 22482334
TI  - Relationship of cardiovascular complications with level of consciousness in
      patients with acute carbamazepine intoxication.
AB  - BACKGROUND: Carbamazepine is an iminostilbene derivative structurally related to
      cyclic antidepressants which implies its potential cardiotxic properties,
      especially in acute poisoning. This study aimed to determine the frequency and
      severity of cardiovascular complications in carbamazepine intoxication and its
      relationship with level of consciousness. METHODS: Patients with carbamazepine
      intoxication referred to our department recruited using convenience sampling
      method. Analysis included following parameters: systolic (SBP) and diastolic
      (DBP) blood pressure, ECG parameters: heart rate (HR), QRS width, PR interval and
      corrected QT interval (QTc). Relations between features on admission, 12 and 24
      hours later and level of consciousness evaluated. RESULTS: 77 patients (28 males,
      49 females; median age 25.1) which got our criteria included in this study. QRS
      complexes in 9 cases (11.7%) were wider than normal and PR interval and corrected
      QT interval (QTc) were normal. There was no significant relationship between QT
      interval, QRS width and pulse rate changes with level of consciousness during 24
      hours post admission, but blood pressure [systolic, diastolic and mean arterial
      blood pressure (MABP)] progressively decreased and PR interval changes
      progressively increased during this period. Further, there was negative
      correlation just between sever decrease of level of consciousness (coma) and
      blood pressure [systolic, diastolic and mean arterial blood pressure (MABP)], and
      positive correlation with QRS complexes widening at 12 hours after admission.
      There was no correlation between loss of consciousness and diastolic blood
      pressure, QT interval and PR interval on admission and 12 hours and 24 hours
      later. CONCLUSION: Regarding the relationship between level of consciousness and
      cardiovascular changes at 12 hours after admission, particular attention on
      cardiovascular changes and ECG monitoring particularly in intoxicated patients
      with severe loss of consciousness(coma), should considered; it will lead to
      prevent unexpected complication, mortality and to decrease the length of
      hospitalization.

PMID- 22482335
TI  - The effects of folic acid on markers of endothelial function in patients with
      type 1 diabetes mellitus.
AB  - BACKGROUND: Endothelial dysfunction is considered as a fundamental and also
      preventable factor in the progression of vascular complications among type 1
      diabetic patient. It occurs before the clinical manifestation of the mentioned
      complications. The aim of this study was to evaluate the effects of folic acid on
      endothelial function by measurements of adhesion molecules and von Willebrand
      factor (vWF) in patients with type 1 diabetes in Isfahan, Iran. METHODS: This
      double blind, placebo-controlled crossover trial included type 1 diabetic
      patients aged 5-20 years old. Selected patients were randomized into two groups
      of A and B to receive folic acid 5 mg daily or placebo for 8 weeks. After a 2
      week washout period, patients in the two groups were swapped to receive placebo
      or folic acid, respectively, for another 8 weeks. Blood and urine samples were
      taken to evaluate glycosylated hemoglobin (HbAlc), folic acid, vWF, intracellular
      adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and
      microalbuminuria levels. Results of these measurements were compared in the two
      groups before and after folic acid and placebo administrations. RESULTS: Fifty
      five type 1 diabetic patients aged 12.1 +/- 3.4 years with diabetes duration of
      3.9 +/- 2.1 years were enrolled. Mean of folic acid level in the two studied
      groups was increased significantly (10.1 +/- 3.8 vs. 21.2 +/- 1.1 in group A and
      15.5 +/- 1.9 vs. 19.9 +/- 2.8 in group B, p < 0.05). Mean of VCAM and
      microalbuminuria was decreased significantly after folic acid administration in
      the two groups (p < 0.05). Mean of HbA1c, ICAM and vWF did not significantly
      change after folic acid administration in the two groups (p > 0.05). CONCLUSION:
      Folic acid administration decreased the level of endothelial dysfunction measured
      by adhesion molecules, especially VCAM and microalbuminuria. However, it did not
      significantly affect vWF. Further studies with larger sample size and long-term
      administration of folic acid are necessary for making precise decisions in this
      field. Key words: endothelial function, Diabetes Mellitus, folic acid.

PMID- 22482336
TI  - Frequency of superficial and deep vein thrombosis in patients with variations of
      superficial veins of lower extremities.
AB  - Anatomical variations of veins often play a crucial role in formation of
      thrombotic changes in superficial and deep veins of lower extremities. THE AIM of
      this study was to determine the frequency of the dominant type of the lower
      extremity superficial veins, and to determine the eventual influence of such
      variations to the formation of superficial and deep vein thrombosis (DVT).
      MATERIAL AND METHODS: The sample used in this study consisted of 180 patients
      subjected to ascedent contrast phlebography of lower extremities. The total
      sample was divided into following groups: patients with and without variations of
      the lower extremity superficial veins. RESULTS AND DISCUSSION: Dominant type of
      the superficial veins (without variation) consisted of 97 patients (53.89%),
      while the rest of 83 patients showed some kind of anatomical variation (46.11%).
      The most frequent variation was the duplicated form ofv. saphena magna in 53.85%,
      while this procentage in women was 57.89%. Most frequent variations of duplicated
      v. saphena magna were: simple duplicated form, closed loop form, branching form
      and combined form. Topographical variation of saphenopopliteal junction besides
      fossa poplitea in the group of men showed procentage of 53.85%, while in the
      group of women that value accounted 63.16%. CONCLUSION: The percentage of
      varicose veins was more frequent in men and women without variations, but deep
      vein DVT showed higher frequency in patients with anatomical variations of
      superficial veins of lower extremities.

PMID- 22482337
TI  - Importance of certain pro-inflammatory indices in patients with liver cirrhosis
      and bacterial infection on prognosis and course of the disease.
AB  - INTRODUCTION: Certain pro-inflammatory indices serum levels, such as leucocytes
      count and C-reactive protein appears to be a significant and simple clinical tool
      in prediction of unfavorable course of liver cirrhosis, its complications due to
      the bacterial infections, length ofhospitalisation and lethal outcome. Cirrhotic
      patients often have a complications due to bacterial infection, demanding the
      unexpected need for hospitalization in 30% to 50% of the cases. THE AIM of this
      study was to assess the impact of pro-inflammatory indices in patients with liver
      cirrhosis, in relation to bacterial infection and their evaluation as possible
      prognostic factors on functional liver deterioration, length of hospitalization
      and lethal outcome. MATERIAL AND METHODS: The research was conducted as a
      prospective study, on 120 patients with liver cirrhosis, who were in divided into
      two groups: I-experimental one of 60 patients with bacterial infection and II
      control one of 60 patients, with no infectious complications diagnosed end
      treated in period 2005.-2010. Year. RESULTS: Most of the patients of experimental
      group were in C stage of disease, compared to those in the control one (p <
      0.001). They had also, initially significantly higher increased values of pro
      inflammatory indices, which were significantly reduced during the treatment (p <
      0.001), with average longer length of hospitalisation and lethal outcome (p <
      0.001; p < 0.01). CRP and the Le count values were most significant predictive
      factors for length of hospitalisation and lethal outcome. DISCUSSION: Pro
      inflammatory indices values may predict an unfavorable course and lethal outcome
      in cirrhotic patients with bacterial infections. Prevention of bacterial
      infection in those patients improves their long-term survival, achieving the
      slower course of the underlying disease.

PMID- 22482338
TI  - Social support and diabetes control: a study among patients admitted to
      specialized clinic of Dr. Gharazi hospital in Isfahan.
AB  - INTRODUCTION: Diabetes causes premature mortality, disability and sometimes
      irreversible health consequences. Scholars believe that social factors directly
      and indirectly could impact patient in control of diabetes. The main purpose of
      this research is to understand how social support related to control of diabetes.
      METHODS: 320 diabetic patients were randomly chosen from specialized clinic of
      Dr. Gharazy hospital in Isfahan. The element was questionnaire which its
      reliability was calculated according to coefficients Cronbach's alpha (r = 0.78).
      The patients 'two previous sessions 'blood sugar level and also their HbA1C were
      studied via referring to their medical records. Then the patients were
      categorized into successful and unsuccessful groups in controlling the diabetes.
      Their relationship of social support and diabetes control was analyzed through
      SPSS software. RESULTS: The findings show that there is a direct relationship
      between social support and control of diabetes. The patients who had better
      instrumental, emotional and informational social support, better controlled their
      diabetes.

PMID- 22482339
TI  - Alexithymia and functional gastrointestinal disorders (FGID).
AB  - NTRODUCTION: The purpose of this study was to examine alexithymia symptoms,
      demographic variables and the severity of gastrointestinal symptoms in a sample
      of patients with functional gastrointestinal disorders (FGID) and a comparative
      sample of healthy controls. MATERIALS AND METHODS: The sample consisted of 237
      individuals, 129 of whom were patients diagnosed with FGIDs. The patients
      referred to the psychosomatic disorders clinic_of Nour Hospital, Isfahan, Iran.
      The controlled group included 108 healthy individuals (without digestive
      diagnosis) matched with the patients by age, gender, marital and educational
      status. The Toronto Alexithymia Scale (TAS-20) and the Gastrointestinal Symptoms
      Rating Scale (GSRS) were used to collect data. Data was analyzed using
      multivariate analysis of variance (MANOVA), correlation coefficients and Fisher's
      z. RESULTS: There was a significant difference between patients with FGIDs and
      healthy controls in terms of number of alexithymia symptoms and severity of
      gastrointestinal symptoms. The results also indicated the existence of a
      relationship between educational level and alexithymia as well as its dimensions
      (difficulty identifying feelings and difficulty describing feelings) in both
      groups. However, no significant differences were found between the two groups in
      this regard. CONCLUSION: The findings of this study indicated that compared to
      the healthy control group, patients with FGIDs had higher scores of alexithymia
      and more severe somatic symptoms. Furthermore, higher educational levels were
      associated with decreased risk of alexithymia. Such finding might be due to
      higher ability to describe and identify emotions in patients with higher levels
      of education.

PMID- 22482340
TI  - Falls in hospitalized acute stroke patients.
AB  - THE AIM of this study was to analyze the fall frequency and some of its
      characteristics in hospitalized acute stroke patients. PATIENTS AND METHODS: It
      was analyzed 1809 acute stroke patients hospitalized at the Department of
      Neurology in period of one year. A fall was defined as any unplanned "touch to
      the floor" of any part of a patient's body, excluding the feet. RESULTS: Out of
      1809 acute stroke patients, 1544 (85.35%) had cerebral infarction (CI) and 265
      (14.65%) intracerebral hemorrhage (IH). In group of patients that fell (61/3.3%),
      49 (80.33%) had infarction and 12 (19.67%) (p = 0.25) had hemorrhage. Out of 61
      patients that fell, 42 (68.86%) suffered from impaired spatial orientation and 47
      (77.05) were aphasic. The neurological deficit, impairments of spatial
      orientation and presents of aphasia were highly correlated with falls (p <
      0.001). The most frequent falls occurred by night night (38 or 62.29%) and in the
      first five days of hospitalization (44 or 72%). In most cases (52%) the falls
      caused minor injuries like contusion and lacerations of skin and did not require
      special medical treatment. CONCLUSION: Hospitalized acute stroke patients have no
      high risk of falling (3.3%), and the incidence of serious injury is low. The
      falls are more frequent in the first five days of hospitalization (72%) and occur
      mostly during the night (62.29%). Severity of neurological deficit, impaired
      spatial orientation and aphasia are highly correlated with falls.

PMID- 22482341
TI  - The Iranian parents of premature infants in NICU experience stigma of shame.
AB  - INTRODUCTION: To explore experiences of Iranian parents with a hospitalized
      premature infant in Neonatal Intensive Care Unit (NICU) and examine socio
      cultural factors associated with having a less than perfect infant. METHODS:
      Purposely selected 21 participants in this study were 6 fathers, 7 mothers, 5
      nurses and 3 physicians specialized in neonatology. Semi-structured in-depth
      interviews using inductive approach and content analysis helped obtain and
      analyze data by open encoding for classification and theme abstraction. RESULTS:
      Findings revealed that parents of hospitalized NICU infants in Iran experienced:
      job and income loss; shattered confidence in parental role; challenges to family
      dynamics; shame as a social stigma; loss of control; overwhelmed with
      uncertainties; and stress induced physical and emotional problems. CONCLUSION:
      Unique and outstanding finding of this study was the social stigma of shame for
      parents of an NICU infant which directly explained the socio-cultural aspect of
      Iranian society where families place great importance on having a healthy and
      strong infant. Having a premature infant with anomalies is viewed as a family
      flaw. Physicians and nurses must focus more on communication with parents and
      fulfill an important role to educate, assure and comfort parents. Establishing
      support system for parents of NICU infants seem urgently needed to improve parent
      infant bonding.

PMID- 22482342
TI  - Influence of the prostate volume, prostate specific antigen density and number of
      biopsy samples on prostate cancer detection.
AB  - AIM: Establish the main differences in the prostate volume, prostate specific
      antigen density (PSAD), number of biopsy samples in patients with primarily or
      rebiopsy detected prostate cancer. MATERIALS AND METHODS: In the 2007-2009
      period, at the KCUS Urology Clinic, there were 379 TRUS guided prostate biopsies
      in 323 patients with known prostate volume. The total of 56 patients (17.3%)
      underwent the first rebiopsy, primarily due to precancerous lesions. The mean
      prostate volume, ranges of prostate size, PSAT, PSAD and the number of biopsy
      samples were analysed retrospectively, and the main characteristics in patients
      with primarily and rebiopsy diagnosed Pca were evaluated as well. RESULTS: The
      first biopsy cancer detection rate was 29.6% (112/379). The rebiopsy detection
      rate was 30.3%. There was no statistically significant difference in the prostate
      volume and the number of biopsy samples among the total number of patients with
      prostate cancer against the group with benign (suspected) findings. There was a
      higher Pca detection rate in patients with the prostate volume < 40 cm3 and 40-60
      cm3, against the group with the prostate volume > 60 cm3. PSAD was significantly
      higher in patients with PCa (0.24 vs. 0.18; p = 0.013). The total of 27.2% of the
      patients with negative biopsy findings and 48% of the patients with diagnosed Pca
      had PSAD > 0.15. PSAD showed sensitivity and specificity in prostate cancer
      detection of 50% and 75%, with PPV of 48%. Furthermore, the patients with PSAD
      >0.15 had a higher Gleason score versus the patients with PSAD < 0.15 (6.7 +/-
      2.4 vs. 5.9 +/- 1.7; p < 0.003). A comparison of the main characteristics in
      patients with primarily and rebiopsy detected prostate cancer gave a
      statistically significant difference only in the number of biopsy samples (10.9
      vs. 14.1, p <.0000). CONCLUSION: Patients with a smaller prostate volume, lower
      PSAD and a higher number of biopsy samples in rebiopsy have a higher chance of
      prostate cancer detection. PSAD carries a higher specificity in rebiopsy
      decision, and a higher PSAD is related to a higher Gleason score.

PMID- 22482343
TI  - Determination of prostate cancer risk factors in Isfahan, Iran: a case-control
      study.
AB  - BACKGROUND: This study was conducted in order to determine the risk factors of
      prostate cancer in Isfahan, Iran. METHODS: In this case-control study 95 cases of
      incident, pathologically confirmed PC and 95 controls were recruited. Odds ratios
      (OR) and the corresponding 95% confidence intervals (CIs) were estimated using
      conditional logistic regression models. RESULTS: The risk of prostate cancer
      increased with increasing age (OR: 1.09, 95% CI: 1.04-1.13; p < 0.001). A
      positive family history of prostate cancer was also a significant risk factor
      (OR: 2.5, 95% CI: 1.1-2.9; p = 0.03). Increased dietary intake tomato sauce was
      associated with a significantly declined risk of prostate cancer (OR: 0.05, 95%
      CI: 0.01-0.40; p < 0.001). Prostate cancer risk was not affected by Smoking,
      alcohol consumption, history of vasectomy, diabetes mellitus, sexually
      transmitted diseases, and dietary garlic and fat intake. CONCLUSIONS: We found
      that increased age and positive family history of prostate cancer could be
      considered as some potential risk factors of prostate cancer in the studied
      population. Moreover, a higher intake of tomato sauce was found to have a
      protective effect against prostate cancer. Key words: Prostate cancer, risk
      factor, Iran.

PMID- 22482344
TI  - Benzodiazepines co-ingestion in reducing tricyclic antidepressant toxicity.
AB  - AIM: Tricyclic antidepressant (TCA) overdose is generally associated with central
      nervous system (CNS) and cardiovascular toxicity manifested by seizure,
      electrocardiographic (ECG) abnormalities and arrhythmia. The objective of this
      study was to determine whether TCA toxicity would be reduced in patient where
      benzodiazepine (BDZ) was co-ingested with TCA. DESIGN: Patients who were
      diagnosed to be poisoned by ingestion of both a tricyclic antidepressant and
      benzodiazepine (TCA-BDZ), and patients intoxicated solely by a TCA were assessed,
      provided that they had one or more clinical signs of toxicity (anticholinergic,
      cardiovascular or CNS findings) and no underlying cardiac disease. TCA poisoned
      patients who had ingested any drugs other than benzodiazepines were excluded.
      Patients transferred from elsewhere and those admitted after the first 24 hours
      were also excluded. The clinical manifestations of TCA toxicity and outcome of
      the patients poisoned only with TCA (N = 60) were compared with those of the
      patients who had co-ingested TCAs and BDZs (N = 60). MAIN RESULTS: The frequency
      distribution of sinus tachycardia, "QRS more than 100 ms, R/S aVR equal or more
      than 0.7, RaVR equal or more than 3 mm", arrhythmia, and generalized tonic
      colonic seizure was less in patients who had co-ingested BDZ with TCA. Evaluating
      the relationship between ingested TCA dosage and electrocardiographic findings
      (duration of QRS, QT and PR intervals, the amplitude of R wave in lead aVR and
      right axis deviation) in both study groups, demonstrated that there was a strong
      relationship between TCA dosage and QRS duration in the TCA group. This was
      significantly different from the same correlation in the TCA-BDZ group (r, 0.50
      in TCA group versus r, 0.04 in TCA and BDZ group, P < 0.05). No significant
      differences were found in complications (aspiration pneumonia, non-cardiac
      pulmonary oedema and death) between the two groups. CONCLUSIONS: cardiovascular
      toxicity and seizure may be less in TCA-BDZ poisoned patients compared with
      patients intoxicated with TCA-alone.

PMID- 22482345
TI  - Wait time in emergency department (ED) processes.
AB  - INTRODUCTION: Emergency Department (ED) provides urgency clinical and Para
      clinical care for patients who injured in accidents and incidents. Simulation is
      one of the decision supporting techniques that analyze risk factors and
      strategies in decision-making. GOAL: The aim of this study was to determine the
      waiting time in emergency department services at Ayatolahkashani Hospital to
      propose scenarios for reducing waiting time. METHODS: This study was an
      analytical and cross-sectional in which data collected by forms and observations.
      Population included waiting and service time in all stations related to ED's
      treatment processes along with diagnostic departments (e.g. Laboratory,
      Radiology, Ultrasonography, and C-T Scan) over a two-week period for 663
      patients. For data analysis, SPSS software and simulation technique were used.
      RESULTS: Results show that add one intern to the Ear Nose Throat (ENT) service
      makes the most reduction on the waiting time from 112.19 to 99.24 minutes. In
      this option the mean of ENT services time will be reduced to 26.54 minutes,
      neurology services time will be reduced to 6.58 minutes and the mean of
      orthopedic services time were reduced to 5.98 minutes. CONCLUSION: Health care
      managers, in the ED are usually physicians who are not familiar with principals
      of management. Hence, they need simple tools for logical decision-making.
      Operation research methods such as simulation should be suitable for them.

PMID- 22482346
TI  - Efficacy of tibial proximal osteotomy in correction of lower limb alignment
      indexes in patients with osteoarthritis in medial compartment of knee.
AB  - NTRODUCTION: Tibial proximal osteotomy is one of the treatments for patients with
      knee compartment osteoarthritis. Studies showed 80% good prognosis in five years
      follow up after osteotomy. Almost always this method is used for pure medial knee
      compartment osteoarthritis that has a varus deformity. THE AIM of all methods is
      reforming varus deformity and lower limb alignment to gain 3 to 5 degree extra
      reformation and take knee in 10 degree valgus. One of the main etiologies for
      patients inconvenience and no decreasing in their pain is overcorrection or
      undercorrection, but unfortunately these can't be noticed. Therefore we must make
      sure that additional stress on the medial joint line was eliminated and
      regeneration of cartilage was facilitated or at least occurrence of
      osteochondritis was decreased. So we aimed to determine the efficacy of tibial
      proximal osteotomy in lower limb alignment indexes in patients with
      osteoarthritis in medial compartment of knee. MATERIAL AND METHODS: This study is
      a clinical trial study that has done in Alzahra University Hospital of Isfahan
      Medical Science University in Iran since June 2010 till February in 2011.
      Patients had pain, pure medial knee compartment osteoarthritis and varus
      deformities were determined for study. Patients who wouldn't come for control,
      those who had no convenience for giving their data or osteoarthritis of all three
      compartments were excluded from study. Number of patients has determined 40
      persons according to previous studies. Sampling occurred convenient. Before any
      surgical processes, the AP x-ray radiography was applied for alignment view. The
      demographic and radiographic data was registered. Six months later we applied AP
      x-ray radiography again and obtained data and analysis them with SPSS software
      and T-Paired statistical method. RESULTS: The mean of anatomical limb angle
      before and after surgical process were 5.1 +/- 3.4 varus and 11.9 +/- 3.4 degree
      valgus, respectively,so with T-test there was a significant difference between
      them (P < 0.001). The mean of mechanical limb angle before and after surgical
      process were 12.6 +/- 3.4 varus and 4.75 +/- 3.5 degree valgus, respectively.
      Therefor with T-test, there was significant difference between them (P < 0.001).
      CONCLUSION: Results were achieved from this study showed that Tibial proximal
      osteotomy is appropriate treatment for young and middle age patients with
      progressive deformity, symptomatic varus knee. Key words: Tibial proximal
      osteotomy, Knee, Osteoarthritis, Varus deformity.

PMID- 22482347
TI  - New method for maximum mobilization of temporalis muscle flap.
AB  - INTRODUCTION: Pedicled temporalis muscle flap presenting a good flap for closing
      large craniofacial defects. Careful surgeons usually do not mobilize temporalis
      muscle flap enough to make appropriate use, fully closure, especially if defect
      exceeds the median line. PATIENTS AND METHODS: Temporalis flap was used in 16
      patients, ages ranged between 12 and 76. In all cases defect reconstruction was
      done by useing new method of extending standard temporal muscle flap. During
      surgical procedure it is very important to keep periosteal elevator in close
      contact with the bone. Then, there is no risk for pedicle injury. After vascular
      pedicle is identified elevating temporal muscle has to be continued by releasing
      the muscle insertion from the coronoid process. By this way, flap length and arc
      of rotation is increased. RESULTS: The flap remained viable in all instances.
      Most of the patients experienced no perioperative complications. There was no
      major complications or mortality as a result of performed procedures. CONCLUSION:
      With this division, flap length was increased at least 2 cm wich is enough for
      covering defects crossing the midline. Instead of using bilateral temporalis
      muscle flaps for defect closure, unilateral is sufficient. With this extension of
      the pedicle length now rotation point is not at the level of the zygomatic arch
      but lower part mandibular neck.

PMID- 22482348
TI  - Treatment of eyelid injuries during period 2008-2010 at eye clinic of clinical
      center University of Prishtina.
AB  - INTRODUCTION: In the Eye Clinic during 2008-2010 we have treated 446 patients,
      where 252 were hospitalized patients while 184 weren't. Treated patients were 1
      85 years old. AIM OF THIS STUDY: AIM OF THIS STUDY is to present our experience
      in treatment of patients with eye lids injuries and their reconstruction.
      MATERIAL AND METHODS: In patients that were treated in the Eye Clinic, we have
      applied surgical methods, anti-tetanic protection and local and general medical
      therapy. 252 hospitalized patients also had other injuries of eye such as:
      rupture of bulbus, traumatic cataract, prolapsus iris, hyphaema in CA, prolapsus
      CV, VLC perforanc cornea et corpus alieni in CA, hyphaema totalis, VLC sclera,
      corpus alieni intrabulbares. RESULTS AND CONCLUSION: Patients that weren't
      hospitalized were 5-10 years old, 25-35 years old and 20-25 years old.
      Hospitalized patients were 5-10 years old, 20-25 years old and 30-35 years old.
      By this we can conclude that there wasn't any significant difference based on the
      patients' age. In the hospitalized cases with eye-lid injuries, most injuries of
      the eye were: VLC perforanc cornea cum prolapsus iridea, Corpus alieni in CA et
      hyphaema.

PMID- 22482349
TI  - Embolism in retinal circulation after invasive cardiovascular procedures.
AB  - To determine the occurence of embolism in retinal circulation after invasive
      cardiovascular procedures and the risk of central retinal artery occlusion (CRAO)
      and branch retinal artery occlusion (BRAO). MATERIAL AND METHODS: During a 3
      month period 153 patients (303 eyes)--101 male/52 female--who had undergone
      coronarography or stent implantation were examined before and 24 hours after the
      procedure. Best corrected visual acuity (BCVA) was taken, visual field
      examination was done and fundoscopy was performed. Eyes with the opacities in the
      anterior segment (corneal leucoma, dense cataracts) were excluded from the study.
      Prior to invasive procedure none of the patients had embolism in the retinal
      circulation. RESULTS AND DISCUSSION: Embolism was found in 3 patients (male) who
      all had hyperlipidemia with normal blood pressure. Two of them had coronarography
      and one patient had stent implantation. One of the patients had a previous branch
      retinal vein occlusion (BRVO) that was treated with photocoagulation. They did
      not report any symptoms. BCVA was the same before and after the procedure. Two of
      the emboli were located in the first branch of the central retinal artery and one
      was located in the branch of cillioretinal artery. All of the emboli were
      transient after 48 hours. CONCLUSION: The study showed that invasive
      cardiovascular procedures do have the risk of developing transient embolism in
      retinal circulation. However, there have been reports of CRAO and BRAO after
      diagnostic cardiac procedures, therefore clinicians should be aware of this
      potential complication.

PMID- 22482350
TI  - Pulmonary vein thrombosis after metastatic liposarcoma.
AB  - Pulmonary vein thrombosis has been described in several patients including those
      with malignancy, pulmonary veno-occlusive disease, fibrosing mediastinitis, and
      after lung transplantation. 1-5 Although liposarcoma frequently metastasizes to
      the lungs, to our knowledge pulmonary venous (tumor) thrombosis with lung
      infarction has not been previously mentioned as part of this disease. We report a
      case of liposarcoma with pulmonary metastases with secondary pulmonary venous
      (tumor) thrombosis and infarction, presenting 3 years after diagnosis of the
      original tumor.

PMID- 22482351
TI  - Acellular dermal matrices in breast implant surgery: defining the problem and
      proof of concept.
AB  - The use of acellular dermal matrices (ADMs) has become a useful adjunct to
      implant-based breast reconstruction and revision of the augmented breast. In both
      instances, the goal is replacement or reinforcement of thinned or missing tissues
      for implant support and control of the implant pocket. This article reviews the
      factors that contribute to periprosthetic tissue thinning, and the advantages and
      limitations of the use of ADMs for revision breast surgery and breast
      reconstruction. Proof of concept for the use of ADMs in the periprosthetic space
      is detailed from early clinical experience and histologic analysis documenting
      vascular ingrowth and cellular repopulation.

PMID- 22482352
TI  - Do acellularized dermal matrices change the rationale for immediate versus
      delayed breast reconstruction?
AB  - This article focuses on the contribution of acellular dermal matrices (ADMs) to
      immediate breast reconstruction. The current literature on ADMs is reviewed and
      the potential advantages and disadvantages of their use are highlighted.
      Technical considerations on how to effectively use these materials is presented.

PMID- 22482353
TI  - Direct-to-implant breast reconstruction.
AB  - The expectations for improved results in postmastectomy reconstruction for women
      have increased in the past decade. The modified radical mastectomy has given way
      to breast conservation techniques using principles of skin preservation. Skin
      sparing and nipple-sparing mastectomies have allowed plastic surgeons to perform
      breast reconstruction with the advantage of an intact skin envelope. Acellular
      dermal matrix is a biotechnological tissue prepared from either human or porcine
      skin. During processing, the cellular components that cause rejection and
      inflammation are removed, producing a structurally intact tissue matrix that
      serves as the biologic scaffold necessary for tissue ingrowth, angiogenesis, and
      tissue regeneration.

PMID- 22482354
TI  - The role of acellular dermal matrix in the treatment of capsular contracture.
AB  - Capsular contracture is one of the most common complications following breast
      surgery with implants and is a common cause for reoperation. Many techniques have
      been described to treat or prevent recurrent capsular contracture with varying
      success. Acellular dermal matrix (ADM), in combination with periprosthetic
      capsulectomy, is a powerful tool to delay or prevent recurrent contracture.
      Excellent results have been obtained when this approach has been used in patients
      with capsular contracture, but at increased cost.

PMID- 22482355
TI  - Pocket reinforcement using acellular dermal matrices in revisionary breast
      augmentation.
AB  - Revision breast augmentation to treat implant malposition is fraught with
      challenges. This article focuses on treatment of implant malposition by using
      acellular dermal matrices (ADMs) with the intent of creating more reliable and
      accurate results. The article discusses the use of ADMs in patients with breast
      implant complications such as bottoming out, lateral implant displacement, or
      synmastia. ADM is a foreign material, thereby adding potential complications to
      consider.

PMID- 22482356
TI  - The use of human acellular dermal matrices in irradiated breast reconstruction.
AB  - This article examines the effects of radiation on prosthetic breast
      reconstruction when human dermal allograft is used in the reconstruction. A brief
      review of radiation terminology and techniques as applied to the breast is given,
      followed by a review of the effects of radiation on wound healing in human
      tissue. The effects of radiation on prosthetic breast reconstruction before the
      advent of dermal allografting are reviewed. The addition of dermal allograft in
      reconstruction has led to a reduced number of complications. An algorithm for
      surgical treatment of irradiated prosthetic breast reconstructions is presented,
      with a discussion of the authors technique.

PMID- 22482357
TI  - Emerging applications for acellular dermal matrices in mastopexy.
AB  - This article explores whether some new acellular dermal matrices (ADMs) can be
      applied to breast augmentation or reconstruction revision, and particularly
      whether they can withstand the centripetal pull and prevent recurrent stretch
      deformities following periareolar mastopexy. Acellular dermis use in breast
      reconstruction and aesthetic breast revision is a fortuitous development, because
      their original purpose was for burn reconstruction. Although level 1 evidence
      remains lacking, ADMs have become integral adjuncts in breast reconstruction,
      complex hernia, and aesthetic breast revision. New applications continue to be
      explored, although these are in early stages of development and their long-term
      value remains to be confirmed.

PMID- 22482358
TI  - Comparison of different ADM materials in breast surgery.
AB  - This is a brief review of the history of the role of acellular dermal matrices in
      breast reconstruction surgery, with a summary of several currently available
      products, including a table of comparisons. Key features, including biologic
      tissue source, surgical preparation, sterility, polarity, contraindications,
      shelf life, and cost, are examined. A paucity of data exists to directly compare
      AlloDerm(r), DermaMatrix(r), StratticeTM, PermacolTM, DermACELL, FlexHD(r),
      SurgiMend(r), and ALLOMAXTM for breast reconstruction; most studies relate to
      hernia repair. An ideal acellular dermal matrix product is still unavailable but
      the information provided in this review should facilitate a breast surgeons
      decision-making process.

PMID- 22482359
TI  - Acellular dermal matrices in breast surgery: tips and pearls.
AB  - Acellular dermal matrices (ADMs) have been used for postmastectomy breast
      reconstruction, primary and secondary breast augmentation, and reduction
      mammaplasty. In postmastectomy breast reconstruction, ADMs can be used to either
      create an implant pocket in single-stage reconstruction or to create the
      inferolateral portion of the tissue expander pocket in two-stage reconstruction.
      Specific deformities after cosmetic breast augmentation such as contour
      irregularities and implant malposition can be addressed with ADMs. The use of
      ADMs is a safe alternative for the correction of breast deformities after
      reconstructive and aesthetic breast surgery.

PMID- 22482360
TI  - Acellular dermal matrices: economic considerations in reconstructive and
      aesthetic breast surgery.
AB  - This article is a review of cost considerations and outcomes pertaining to the
      use of acellular dermal matrices (ADMs) in reconstructive and aesthetic breast
      surgery. The history of the use of ADMs in breast surgery and all case series
      describing outcomes and use of ADM in breast reconstructive and aesthetic surgery
      are reviewed. Weighted averages for clinically relevant outcomes for
      reconstructive and aesthetic breast surgery are provided. Cost considerations of
      ADM use in breast surgery are described and as an example, a single institution's
      experience with implementation of ADM into a preexisting breast surgery program,
      is used.

PMID- 22482361
TI  - Current state of the art for acellular dermal matrices in breast surgery.

PMID- 22482362
TI  - Potential anticancer activity of myricetin in human T24 bladder cancer cells both
      in vitro and in vivo.
AB  - Myricetin, a naturally occurring phytochemical, has potent anticancer-promoting
      activity and contributes to the chemopreventive potential of several foods. In
      this preliminary study, we evaluate the chemopreventive potential of myricetin
      against bladder cancer and its mechanism of action. The results of a MTT assay
      showed that myricetin was able to inhibit the viability and proliferation of T24
      cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at
      G2/M in a dose-dependent manner and induced apoptosis detected by flow cytometry
      and DNA fragmentation analysis. Treatment with myricetin led to G2/M cell cycle
      arrest in T24 cells by downregulation of Cyclin B1 and cyclin-dependent kinase
      cdc2. Myricetin-induced apoptosis correlates with the modulation of Bcl-2 family
      proteins and activation of the caspase-3. Myricetin also inhibited the
      phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced.
      Myricetin had a significantly reduced T24 cell migration that was accompanied by
      a decreasing MMP-9 expression in vitro. Furthermore, myricetin treatment
      significantly inhibited the tumor growth on T24 bladder cancer xenografts model.
      These findings suggest that myricetin has potential anticancer activity and could
      be an important chemoprevention agent for bladder cancer.

PMID- 22482363
TI  - Molecular dynamics investigation into substrate binding and identity of the
      catalytic base in the mechanism of Threonyl-tRNA synthetase.
AB  - The structure and nature of the fully bound active site of Threonyl-tRNA
      Synthetase (ThrRS) for the second half-reaction has been investigated using
      molecular dynamics simulations. More specifically, we  examined the ThrRS active
      site with both the substrate Threonyl-AMP and the cosubstrate cognate Threonyl
      tRNA bound. Furthermore, we  also considered the cases in which an active-site
      histidyl residue (His309) is either neutral or protonated. Moreover, we 
      considered the role a water molecule may play in  formation of a viable Michaelis
      complex. From the results it is found that the most likely role of His309 is in
      binding and properly orientating the ribose of the Ado76 nucleotidyl residue of
      the threonyl-tRNA via formation of a direct His309...Ado76 hydrogen bond, i.e.,
      without  involvement of a water. In addition, the imidazole of the His309 residue
      is likely neutral. It was found that upon protonation the positioning of the
      Ado76-3'-OH was perturbed, leading to a reduced chance for nucleophilic attack of
      the threonyl's C1 center.

PMID- 22482364
TI  - Feasibility of depth profiling of animal tissue by ultrashort pulse laser
      ablation.
AB  - Experiments were performed to examine the feasibility of mass spectrometry (MS)
      depth profiling of animal tissue by ~75 fs, 800 nm laser pulses to expose
      underlying layers of tissue for subsequent MS analysis. Matrix assisted laser
      desorption ionization mass spectrometry (MALDI-MS) was used to analyze
      phospholipids and proteins from both intact bovine eye lens tissue and tissue
      ablated by ultrashort laser pulses. Laser desorption postionization mass
      spectrometry (LDPI-MS) with 10.5 eV single photon ionization was also used to
      analyze cholesterol and other small molecules in the tissue before and after
      laser ablation. Scanning electron microscopy was applied to examine the ablation
      patterns in the tissue and estimate the depth of the ablation craters. Ultrashort
      pulse laser ablation was found to be able to remove a layer of several tens of
      micrometers from the surface of eye lens tissue while leaving the underlying
      tissue relatively undamaged for subsequent MS analysis. MS analysis of
      cholesterol, phospholipids, peptides, and various unidentified species did not
      reveal any chemical damage caused by ultrashort pulse laser ablation for analytes
      smaller than ~6 kDa. However, a drop in intensity of larger protein ions was
      detected by MALDI-MS following laser ablation. An additional advantage was that
      ablated tissue displayed up to an order of magnitude higher signal intensities
      than intact tissue when subsequently analyzed by MS. These results support the
      use of ultrashort pulse laser ablation in combination with MS analysis to permit
      depth profiling of animal tissue.

PMID- 22482365
TI  - Topologically unique heterometallic Cu(II)/Li coordination polymers self
      assembled from N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid biobuffer:
      versatile catalyst precursors for mild hydrocarboxylation of alkanes to
      carboxylic acids.
AB  - The facile aqueous medium reactions of copper(II) nitrate with BES biobuffer
      [(HOCH(2)CH(2))(2)N(CH(2)CH(2)SO(3)H), hereinafter referred as H(3)bes] in the
      presence of various benzenecarboxylic acids [benzoic (Hba), 3-hydroxybenzoic
      (Hhba), and 3,5-dihydroxybenzoic (Hdhba) acid] and lithium hydroxide gave rise to
      the self-assembly generation of three new heterometallic Cu(II)/Li materials,
      [Li(H(2)O)(4)][Cu(4)(MU(2)-Hbes)(4)(MU(2)-ba)].H(2)O (1) and [Cu(4)(MU(3)
      Hbes)(4)(L){Li(H(2)O)(2)}](n).3nH(2)O {L = MU(2)-hba (2) and MU(2)-dhba (3)}.
      They were isolated as air-stable crystalline solids and fully characterized by
      infrared (IR) and UV-vis spectroscopy and electrospray ionization (ESI)-MS(+/-),
      elemental, thermal, and single-crystal X-ray diffraction analyses. The latter
      revealed that 1-3 have comparable packing patterns and unit cell parameters,
      being composed of similar [Cu(4)(MU-Hbes)(4)(MU-carboxylate)](-) cores and
      [Li(H(2)O)(4)](+) cations (in 1) or [MU-Li(H(2)O)(2)](+) groups (in 2 and 3),
      which are arranged into discrete 0D aggregates in 1 or infinite 3D
      noninterpenetrating metal-organic networks in 2 and 3. The topological analysis
      of the coordination polymers 2 and 3 disclosed the trinodal 3,3,4-connected
      underlying nets with an unprecedented topology defined by the point symbol of
      (4.6.8)(4)(4(2).6)(2)(6(2).16(2).18(2)), further simplification of which resulted
      in the binodal 4,4-connected nets with the pts (PtS) topology. Apart from
      representing very rare examples of coordination compounds derived from H(3)bes, 1
      3 feature solubility in water and were applied as efficient and versatile
      catalyst precursors for the mild (60  degrees C) single-pot hydrocarboxylation,
      by CO and H(2)O, of various gaseous, linear, and cyclic C(n) (n = 2-9) alkanes
      into the corresponding C(n+1) carboxylic acids, in H(2)O/MeCN medium under
      homogeneous conditions and in the presence of potassium peroxodisulfate. Total
      yields (based on alkane) of carboxylic acids up to 78% were achieved, which are
      remarkable in the field of alkane functionalization under mild conditions,
      especially for a C-C bond formation reaction in aqueous acid-solvent-free medium.

PMID- 22482366
TI  - Mutated intramolecular chaperones generate high-activity isomers of mature
      enzymes.
AB  - The propeptide of carboxypeptidase Y precursor (proCPY) acts as an intramolecular
      chaperone that ensures the correct folding of the mature CPY (mCPY). Here, to
      further characterize the folding mechanism mediated by the propeptide, folding
      analysis was performed using a yeast molecular display system. CPYs with mutated
      propeptides were successfully displayed on yeast cell surface, and the mature
      enzymes were purified by the selective cleavage of mutated propeptides.
      Measurement of the activity and kinetics of the displayed CPYs indicated that the
      propeptide mutation altered the catalytic efficiency of mCPY. Although the mature
      region of the wild-type and mutant CPYs had identical amino acid sequences, the
      mCPYs from the mutant proCPYs had higher catalytic efficiency than the wild-type.
      These results indicate that proteins with identical amino acid sequence can fold
      into isomeric proteins with conformational microchanges through mutated
      intramolecular chaperones.

PMID- 22482368
TI  - The growth of one-dimensional CuPcF16 nanostructures on gold nanoparticles as
      studied by transmission electron microscopy tomography.
AB  - The growth of one-dimensional (1D) fluorinated copper-phthalocyanine (CuPcF(16))
      on gold (Au) nanoparticles (NPs) is studied by electron tomography. The shape of
      the 1D structure and its geometrical relationship with the associated Au NP are
      determined by a three-dimensional reconstruction analysis combined with high
      resolution electron microscopy. The CuPcF(16) molecules nucleate at the <110>
      edge of the Au nanoparticle and grow parallel to a {111} facet of the particle
      along a direction close to <121>. This implies that the maximum diameter of the
      1D structure is limited by the width of the <110> edge of the Au particle.

PMID- 22482367
TI  - Peptidolipins B-F, antibacterial lipopeptides from an ascidian-derived Nocardia
      sp.
AB  - A marine Nocardia sp. isolated from the ascidian Trididemnum orbiculatum was
      found to produce five new lipopeptides, peptidolipins B-F (1-5), which show
      distinct similarities to the previously reported L-Val(6) analog of peptidolipin
      NA. Synthetic modification of peptidolipin E (4) was used to determine the
      location of an olefin within the lipid chain. The advanced Marfey's method was
      used to determine the absolute configurations of the amino acids. Peptidolipins B
      (1) and E (4) demonstrated moderate antibacterial activity against methicillin
      resistant Staphylococcus aureus and methicillin-sensitive Staphylococcus aureus.

PMID- 22482369
TI  - Constrained snake vs. conventional snake for carotid ultrasound automated IMT
      measurements on multi-center data sets.
AB  - Accurate intima-media thickness (IMT) measurement of the carotid artery from
      minimal plaque ultrasound images is a relevant clinical need, since IMT increase
      is related to the progression of atherosclerosis. In this paper, we describe a
      novel dual snake-based model for the high-performance carotid IMT measurement,
      called Carotid Measurement Using Dual Snakes (CMUDS). Snakes (which are
      deformable contours) adapt to the lumen-intima (LI) and media-adventitia (MA)
      interfaces, thus enabling the IMT computation as distance between the LI and MA
      snakes. However, traditional snakes might be unable to maintain a correct
      distance and in some spatial location along the artery, it might even collapse
      between them or diverge. The technical improvement of this work is the definition
      of a dual snake-based constrained system, which prevents the LI and MA snakes
      from collapsing or bleeding, thus optimizing the IMT estimation. The CMUDS system
      consists of two parametric models automatically initialized using the far
      adventitia border which we automatically traced by using a previously developed
      multi-resolution approach. The dual snakes evolve simultaneously and are
      constrained by the distances between them, ensuring the regularization of LI/MA
      topology. We benchmarked our automated CMUDS with the previous conventional semi
      automated snake system called Carotid Measurement Using Single Snake (CMUSS). Two
      independent readers manually traced the LIMA boundaries of a multi-institutional,
      multi-ethnic, and multi-scanner database of 665 CCA longitudinal 2D images. We
      evaluated our system performance by comparing it with the gold standard as traced
      by clinical readers. CMUDS and CMUSS correctly processed 100% of the 665 images.
      Comparing the performance with respect to the two readers, our automatically
      measured IMT was on average very close to that of the two readers (IMT
      measurement biases for CMUSS was equal to -0.011+/-0.329mm and -0.045+/-0.317mm,
      respectively, while for CMUDS, it was 0.030+/-0.284mm and -0.004+/-0.273mm,
      respectively). The Figure-of-Merit of the system was 98.5% and 94.4% for CMUSS,
      while 96.0% and 99.6% for CMUDS, respectively. Results showed that the dual-snake
      system CMUDS reduced the IMT measurement error accuracy (Wilcoxon, p<0.02) and
      the IMT error variability (Fisher, p<3*10(-2)). We propose the CMUDS technique
      for use in large multi-centric studies, where the need for a standard, accurate,
      and automated IMT measurement technique is required.

PMID- 22482371
TI  - Asymmetric Michael addition of substituted rhodanines to alpha,beta-unsaturated
      ketones catalyzed by bulky primary amines.
AB  - A bulky group was introduced by design into a diamine catalyst, and a series of
      robust and tunable bulky chiral primary amine catalysts were developed and
      successfully applied in the direct conjugate addition of substituted rhodanines
      to alpha,beta-unsaturated ketones. High yields (up to 99%) and excellent
      diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to 98% ee)
      were observed.

PMID- 22482370
TI  - The in vivo developmental potential of porcine skin-derived progenitors and
      neural stem cells.
AB  - Multipotent skin-derived progenitors (SKPs) can be traced back to embryonic
      neural crest cells and are able to differentiate into both neural and mesodermal
      progeny in vitro. Neural stem cells (NSCs) are capable of self-renewing and can
      contribute to neuron and glia in the nervous system. Recently, we derived porcine
      SKPs and NSCs from the same enhanced green fluorescent protein (EGFP) transgenic
      fetuses and demonstrated that SKPs could contribute to neural and mesodermal
      lineages in vivo. However, it remains unclear whether porcine SKPs and NSCs can
      generate ectoderm and mesoderm lineages or other germ layers in vivo. Embryonic
      chimeras are a well-established tool for investigating cell lineage determination
      and cell potency through normal embryonic development. Thus, the purpose of this
      study was to investigate the in vivo developmental potential of porcine SKPs and
      fetal brain-derived NSCs by chimera production. Porcine SKPs, NSCs, and
      fibroblasts were injected into precompact in vitro fertilized embryos (IVF) and
      then transferred into corresponding surrogates 24 h postinjection. We found that
      porcine SKPs could incorporate into the early embryos and contribute to various
      somatic tissues of the 3 germ layers in postnatal chimera, and especially have an
      endodermal potency. However, this developmental potential is compromised when
      they differentiate into fibroblasts. In addition, porcine NSCs fail to
      incorporate into host embryos and contribute to chimeric piglets. Therefore,
      neural crest-derived SKPs may represent a more primitive state than their
      counterpart neural stem cells in terms of their contributions to multiple cell
      lineages.

PMID- 22482372
TI  - Initial assessment and management of trauma patients: speaking a common language.

PMID- 22482373
TI  - Pre-emptive analgesic and haemodynamic efficacy of combined spinal-epidural
      neostigmine delivery.
AB  - OBJECTIVE: To determine the effect of pre-emptive epidurally administered 4 or 8
      mcg/kg neostigmine on analgesia, mean arterial pressure, heart rate and side
      effects in intra and postoperative period. STUDY DESIGN: Randomized, double
      blinded, controlled clinical trial. PLACE AND DURATION OF STUDY: Ankara Numune
      Training and Research Hospital, Turkey, from January to December 2008.
      METHODOLOGY: Forty-five patients scheduled for lower extremity surgery were
      included in the study following the approval of the ethics committee and the
      patients. The study group was split into three groups and received combined
      spinalepidural anaesthesia. Diluting with 10 ml normal saline, group N4 and group
      N8 were delivered 4 mcg/kg and 8 mcg/kg epidural neostigmine, respectively,
      whereas group SF received 10 ml epidural saline. Lidocaine (2%) at 1.2 mg/kg dose
      was preferred for spinal anaesthesia. Analgesic efficacy, time to first analgesic
      requirement, Visual Analog Scale, Fentanyl consumption in the postoperative
      patient-controlled epidural analgesia, and delivered/required number of boluses,
      were evaluated. Haemodynamic data and side effects were noted. RESULTS:
      Statistically, analgesic consumptions at 12 and 24 hours in the N8 group was
      lower than those in the SF group, the number of delivered boluses was lower in
      the N8 group compared with the SF and N4 groups, number of required boluses was
      lower in the N8 group than in the SF group. In terms of haemodynamics and side
      effects, no difference was found between the groups regarding the entire
      intraoperative and postoperative parameters. CONCLUSION: Epidural Neostigmine
      administration at 8 mcg/kg was found to be a viable additional agent against
      analgesia, with the postoperative period depending on the dosage.

PMID- 22482374
TI  - Response of a single 'mega intramuscular dose' of vitamin D on serum 25OHD and
      parathyroid hormone levels.
AB  - OBJECTIVE: To determine the changes produced in serum 25OHD and iPTH levels after
      600,000 IU of injection cholecalciferol in volunteers. STUDY DESIGN:
      Interventional study. PLACE AND DURATION OF STUDY: Section of Chemical Pathology,
      Department of Pathology and Microbiology, the Aga Khan University Hospital,
      Karachi, from June 2009 - June 2010. METHODOLOGY: Volunteers of either gender
      aged 18-40 years with known 25OHD, calcium (Ca), creatinine (Cr) and phosphorous
      (P) levels were included in the study. Subjects on therapy like vitamin D and
      calcium supplements, corticosteroids or anti-epileptic medicines, primary
      hyperparathyroidism and hypercalcaemia, with co-morbidity like renal failure,
      liver disease and history of malabsorption, diarrhea or hyperthyroidism were
      excluded. All volunteers were given an intramuscular injection of vitamin D3
      (cholecalciferol, 600,000 IU). After 8 weeks, serum 25OHD, iPTH, Ca and P levels
      were determined again. For 25OHD level, cut-off of 2 50 nmol/l was defined as
      deficient, 50-75 nmol/l as insufficient and 3 75 as optimal level. RESULTS: Mean
      25OHD and iPTH levels were 35.06 +/- 16.6 nmol/l and 81.15 +/- 76.78 pg/ml
      respectively at baseline. Seventeen volunteers were 25OHD deficient. Five had
      high iPTH levels (25%) (mean 156 +/- 123.7 pg/ml). 25OHD and iPTH showed a
      significant inverse correlation at baseline (< 0.01). After 8 weeks of injection
      vitamin D 25OHD levels became optimal in 6 subjects (35%) [mean 92.9 +/- 16.6
      nmol/l]. It remained low in 5 volunteers (25%) [mean 41.6 +/- 9.6 nmol/l] while
      insufficient levels were seen in 9 volunteers (40%) [mean 63.3+/-5.8 nmol/l].
      Follow-up mean Ca, P and iPTH were 2.25 mmol/l (+/- 0.09), 1.1 (+/- 0.1) and
      47.52 pg/ml (+/- 22.56) respectively. A significant increase in mean 25OHD level
      was seen at follow-up (p < 0.01), while the change in PTH was insignificant
      (p=0.05). CONCLUSION: Single mega-dose of cholecalciferol achieved optimal levels
      of 25OHD in 35% of subjects after eight weeks of supplementation.

PMID- 22482375
TI  - Combat related vascular trauma.
AB  - OBJECTIVE: To determine the frequency and pattern of different types of vascular
      injuries, their management and surgical complications. STUDY DESIGN: Case series.
      PLACE AND DURATION OF STUDY: Combined Military Hospital, Peshawar, from August
      2008 to August 2010. METHODOLOGY: All patients of vascular injuries were
      included. Traumatic amputation, amputation for extensive soft tissue, or nerve
      injury, death due to reasons other than vascular injuries or Mangled Extremity
      Severity Score (MESS > 7) were excluded from study. Data included patient
      profile, time and date of admission, place, site, type and mechanism of injury,
      associated injuries, vital signs, treatment, type of vascular repair and outcome.
      Decision to operate was mainly based on clinical diagnosis and hand-held Doppler
      finding. RESULTS: There were 170 vascular injuries in 96 patients; 76.4% were
      arterial and 23.5% were venous. Gunshot wounds was main cause (54%) and
      extremities were the commonest site (85%). Arteries were repaired in 87% and
      veins in 40% cases. Venous interposition graft was the preferred method of
      repair. The overall limb salvage rate was 95%. Thrombosis and infection of the
      graft and repair were the main causes of secondary amputation. Haemorrhage,
      reperfusion injury and infection were the main causes of death. CONCLUSION: Every
      effort should be made to repair an injured artery to preserve a limb and life.
      Tourniquet, prophylactic fasciotomy and vascular shunts play an important role.
      Management of life threatening injuries, unstable fracture of long bones and
      debridement before definitive repair of artery is important.

PMID- 22482376
TI  - Awareness among parents of beta-thalassemia major patients, regarding prenatal
      diagnosis and premarital screening.
AB  - OBJECTIVE: To assess the knowledge among parents of thalassemia major patients
      about prenatal diagnosis, premarital screening for carrier detection and impact
      of consanguineous marriage on disease transmission. STUDY DESIGN: Descriptive
      study. PLACE AND DURATION OF STUDY: The Thalassemia Centre, Sir Ganga Ram
      Hospital, Lahore, from July to September 2009. METHODOLOGY: One hundred and
      fifteen parents of beta-thalassemia major patients were enrolled in this study. A
      questionnaire was developed and parents were interviewed to assess their
      knowledge about preventive measures against thalassemia major. Parents of
      patients with all other types of blood disorder were excluded from the study.
      RESULTS: There were 74 male (64.3%) and 41 female (35.7) patients with mean age
      of 9.5 +/- 5.1 years. Eighty-eight patients (76.5%) were accompanied by mothers
      and the rest by their fathers. Seventy-four parents (32.1%) were illiterate;
      among the literates only 7 were highly educated (3%). Ninety-four couples (81.7%)
      had consanguineous marriage. Fiftytwo parents (44.6%) knew that thalassemia is an
      inherited disorder. Thirty-eight (33%) had heard about the test for detecting
      thalassemia carrier. Premarital screening and prenatal diagnosis was known to 97
      (84.3%) and 88 (76.5%) parents respectively. Ninety-nine parents (86.1%) knew
      about the termination of pregnancy on positive prenatal test but only 69
      considered it acceptable religiously (60%). Major source of information to the
      parents were doctors. CONCLUSION: Parental knowledge about thalassemia and its
      preventive measures was inadequate; this requires intervention in the form of
      public health education programs concentrating on high risk/targeted population.

PMID- 22482377
TI  - Medical students' perspective about role-plays as a teaching strategy in
      community medicine.
AB  - OBJECTIVE: To assess the students' perspective about role-plays conducted as a
      teaching methodology in community medicine. STUDY DESIGN: A quasi-experimental
      study. PLACE AND DURATION OF STUDY: Department of Community Medicine at Fatima
      Memorial College of Medicine and Dentistry from July to November 2010.
      METHODOLOGY: A probability technique of simple random sampling was used to
      collect 63 students from the third and fourth year MBBS who were randomly
      distributed in five sub-groups. They were variously ascribed the roles of
      obsceners, participants and helpers. A questionnaire was distributed to collect
      student's responses. The data was analyzed on SPSS version 17 to compare the
      responses. Chi-square test was applied and p-value was fixed at < 0.05 as
      significant. RESULTS: Sixty-three students were selected as participants of this
      study in which 46 belonged to the fourth year MBBS class (73%) and 17 were third
      year MBBS students (27%). There were 13 male (20.6%) and 50 female (79.4%)
      students. Role-plays were identified as most effective method of teaching (n =
      25, 37.9%) followed by lectures (n = 17, 25.8%, p = 0.054). Fifty-two students
      (78.5%) admitted that role-plays improved their knowledge of the subject, 55
      (84.6%) said that it will help them in their clinical performance. Fifty-nine
      participants (89.4%) found role-plays interesting and 49 (74.2%) wanted to
      incorporate role-plays as a part of curriculum. Fifty-six of the participants
      (88.9%) agreed that role-plays improved their communication skills. Twenty-one
      participants (31.8%) believed that it helped them in making acquaintance with the
      local situation. Forty-six students (76.7%) identified role-plays as a feasible
      way of andragogy (p = 0.005) and 48 (76.2%) said that it provoked critical
      thinking about the subject (p = 0.038). Fifty-four students (85.7%) admitted that
      their attention span was better in role-plays as compared to lectures (p =
      0.047). CONCLUSION: Role-plays were well accepted by the students as an effective
      teaching methodology and can be incorporated as a part of teaching strategies in
      Community Medicine.

PMID- 22482378
TI  - Frequency of newly diagnosed diabetes mellitus in acute ischaemic stroke
      patients.
AB  - OBJECTIVE: To determine the frequency of newly diagnosed diabetes mellitus in
      acute ischaemic stroke patients. STUDY DESIGN: Observational study. PLACE AND
      DURATION OF STUDY: Jinnah Postgraduate Medical Centre, Karachi, from June 2007 -
      June 2008. METHODOLOGY: This study included adult patients (age > 30 years, both
      genders) with the diagnosis of acute ischaemic stroke. Patients who were known to
      have diabetes mellitus prior to stroke, had a non-lacunar stroke or were admitted
      to intensive care units for any reason were excluded. Detailed history and
      examination, fasting blood sugar, fasting lipid profile, a non-enhanced CT scan
      brain and electrocardiogram were done on every patient. Data were entered on a
      preformed proforma. The results were analyzed on SPSS version 10. Chi-square test
      was applied. P-value <0.05 was considered to be statistically significant.
      RESULTS: A total of 250 patients were enrolled. The male: female ratio was 1:
      0.9. Mean age was observed as 60.9+/-10.1 years. In total, 50 new cases of
      diabetes mellitus were identified (20%). Average fasting blood sugar in diabetic
      subjects was 148+/-10 mg/dl. The most common risk factors in the newly diagnosed
      diabetic subjects were hypertension 26 (52%), smoking 18 (36%) and hyperlipidemia
      14 (28%). Atrial fibrillation and myocardial infarction were seen in 12 subjects
      (24%) and 9 subjects (18%) respectively. CONCLUSION: Twenty percent patients with
      acute ischaemic stroke had un-diagnosed diabetes. Therefore, it is advisable to
      screen acute stroke patients for diabetes to reduce their long-term morbidity and
      mortality.

PMID- 22482379
TI  - Microaesthetics of The Smile: Extraction vs. Non-extraction.
AB  - OBJECTIVE: To compare microaesthetics in pre- and post-orthodontic cases, treated
      with non-extraction and extraction treatment and assessed whether the achieved
      microaesthetic parameters are comparable to the proposed norms. STUDY DESIGN:
      Quasi-experimental study. PLACE AND DURATION OF STUDY: Orthodontic Clinic, the
      Aga Khan University Hospital, Karachi, from January 2005 to December 2009.
      METHODOLOGY: Orthodontic records of 31 cases treated with non-extraction therapy
      and 26 cases treated with extraction of upper first premolars were selected.
      Patients were of Pakistani origin, aged between 12 to 30 years. Microaesthetics
      was assessed by measuring maxillary central incisor crown width-height ratio,
      connectors between the maxillary anterior sextant, gingival zenith level of the
      maxillary lateral incisor and golden percentage of the anterior teeth using the
      patients' plaster models and intraoral frontal photographs. Measurements of the
      golden percentage were made using the software Adobe Photoshop, whereas all other
      parameters were measured on the plaster casts using a digital vernier caliper.
      Paired t-test, independent t-test and one sample t-test were used to make
      comparisons within the groups, between the groups, and to compare the
      posttreatment values with the proposed norms, respectively. Statistical
      significance level was set at p 2 0.05. RESULTS: A statistically significant
      improvement in the microaesthetic parameters was observed for both extraction and
      non-extraction subjects (p < 0.05) after orthodontic treatment. Values closer to
      the proposed norms were achieved more readily in the non-extraction group.
      CONCLUSION: Microaesthetics of the smile is improved with orthodontic treatment.
      It is recommended that greater consideration be given to the microaesthetic
      parameters of the smile during the finishing stages particularly when utilizing
      extraction mechanics during orthodontic treatment.

PMID- 22482380
TI  - Prevalence of dyslipidemias in autoimmune rheumatic diseases.
AB  - OBJECTIVE: To determine the frequency of dyslipidemias in various autoimmune
      rheumatic diseases and the difference in lipid profile according to the activity
      of these diseases. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF
      STUDY: The Rheumatology Department of Pakistan Institute of Medical Sciences
      (PIMS), Islamabad, from May 2010 to April 2011. METHODOLOGY: All patients who
      presented to Rheumatology Department with various autoimmune inflammatory
      rheumatic diseases were included. Fasting lipid profiles of patients were
      obtained after an overnight fast of 12 hours. Various diseases were classified as
      active or inactive on the basis of clinical features and relevant laboratory
      tests. Data were entered in SPSS 17 and analyzed. Association between disease
      activity and abnormal lipid profile was also determined. RESULTS: A total of 100
      patients were included in the study. Out of these, 82% were females. Mean age was
      34.15 +/- 7.73 years. Rheumatoid arthritis (RA) was the most common disease
      present in 78 patients. Various types of dyslipidemias were found in 54% of
      patients. Low HDL and deranged cholesterol levels were significantly associated
      with active disease (p = 0.044 and p = 0.048 respectively). Patients with RA also
      had dyslipidemias in 45% of the cases. Disturbed cholesterol level was observed
      in active RA (p = 0.044). CONCLUSION: Dyslipidemias are frequent among the
      patients with autoimmune rheumatic diseases (AIRD). Disturbance in total
      cholesterol is the most common abnormality with a significant association with
      disease activity.

PMID- 22482381
TI  - Forensic odontology.
AB  - Forensic odontology is a specialized field of dentistry which analyses dental
      evidence in the interest of justice. Forensic odontology embraces all dental
      specialities and it is almost impossible to segregate this branch from other
      dental specialities. This review aims to discuss the utility of various dental
      specialities with forensic odontology.

PMID- 22482382
TI  - Pain management after traumatic spinal cord injury.
AB  - Pain is experienced by people suffering from spinal cord injury leading to
      disability and affecting the person's functional ability, independence,
      psychological well - being, ability to return to work and quality of life. Pain
      management in these patients is notoriously difficult due to multiple factors and
      varied mechanism leading to pain. Only few treatments have been assessed in
      randomized, controlled trials and management is based on different case reports.
      We are reporting our experience of managing 2 patients with neuropathic pain
      following traumatic spinal cord injury. Both the patients were refractory to
      conventional pain medications but there was significant reduction in pain
      following lignocaine infusion in the first patient and with ketamine in the
      second patient.

PMID- 22482383
TI  - Infective endocarditis: a rare cause of acute coronary syndrome.
AB  - This is a case report of a 26 years old female who presented in emergency with
      sudden onset of chest heaviness and dyspnoea. She had suffered a stroke in the
      past and was treated with anti-tuberculous medication. Her ECG revealed
      STelevation myocardial infarction and thrombolysis was performed but was
      unsuccessful. Further workup during in-hospital stay revealed evidence of
      infective endocarditis and Streptococcus species were isolated. She was started
      on penicillin and gentamycin with good recovery. This case presented a management
      problem during initial presentation as there was insufficient data on
      thrombolysis during such situation. It is also a diagnostic problem as the
      initial picture was dominated by acute coronary syndrome. There is need to
      develop consensus based on expert opinion about management in such situations.

PMID- 22482384
TI  - Left paraduodenal hernia: a rare cause of large bowel obstruction and gangrene.
AB  - Internal hernias are a rare cause of intestinal obstruction. Paraduodenal hernias
      are the most common type of internal hernias. Although small bowel obstruction is
      associated with internal hernias, large bowel obstruction is unique. The authors
      here report a case of left para duodenal hernia with simultaneous small and large
      bowel obstruction and gangrene. The patient underwent emergency laparotomy and
      generous resection of gangrenous small and large bowel was carried out and stoma
      was created. Postoperatively, the patient had a smooth recovery and was
      discharged after a few days.Reversal of stoma was carried out after 2 months.

PMID- 22482385
TI  - Splenic abscess arising from acute cholecystitis.
AB  - Splenic abscess is an uncommon surgical condition and is life-threatening if un
      diagnosed earlier during the course of illness. Splenic abscess has been reported
      in association with hepatic abscess. This report describes a case of splenic
      abscess associated with cholecystitis. Since, the symptoms are generally non
      specific, a high index of suspicion is necessary to diagnose splenic abscess in
      patients having acute or chronic cholecystitis. When such patients have fever and
      left upper quadrant pain, splenic abscess should be considered.

PMID- 22482386
TI  - Nephritis and Charcot-Marie-Tooth disease: an unusual association.
AB  - A 24 years old male, who presented to us with uraemic symptoms secondary to
      chronic glomerulonephritis. On examination, he was found to have features of
      peripheral neuropathy which was confirmed as Charcot-Marie-Tooth type 1 on nerve
      conduction studies. Very few cases of glomerular disease, mainly focal segmental
      glomerulosclerosis have been associated with the Charcot-Marie-Tooth worldwide.

PMID- 22482387
TI  - An unusual cause of recurrent throat pain - calcified stylohyoid ligament.
AB  - Calcified stylohyoid ligament is also called an elongated styloid process and the
      symptom complex that it produces is called Eagle's syndrome. The symptoms of neck
      pain, sore throat, foreign body sensation in the throat, dysphagia and otalgia
      may be confused with other head and neck pain and are often worsened by yawning,
      opening the mouth wide or turning the head laterally. This is the result of
      involvement of cranial nerves, carotid plexus and cervical plexus. Carotid artery
      involvement causes wider symptomatology. Sometimes, it presents as a complication
      of tonsillectomy procedure. Elongated styloid process is conveniently identified
      on firm digital examination of tonsillar fossa. Diagnosis is made with
      appropriate radiological examination. Non-surgical treatment options include re
      assurance, analgesia, anti-inflammatory medications and surgical option is
      shortening of the elongated styloid process by transoral or external approach.
      The condition is hereby described in a 59 years old male.

PMID- 22482388
TI  - Grebe syndrome: a rare association with congenital heart disease.
AB  - Grebe syndrome is a very rare form of short-limbed dwarfism. It is a genetic
      condition, passed by autosomal recessive inheritance. It is characterized by
      marked acromesomelic shortening of all the four limbs. There are no other
      associated anomalies. The affected baby has normal intelligence and normal life
      span. We present here a case of Grebe syndrome along with congenital heart
      disease.

PMID- 22482389
TI  - Giant iliac vein aneurysm secondary to long standing traumatic popliteal
      arteriovenous fistula.
AB  - A 48-year-old man presented with a traumatic arteriovenous fistula (AVF) in the
      left popliteal space, due to a bullet injury 20 years back. A computed
      tomographic (CT) angiography revealed an AVF in the left popliteal space with an
      associated large iliac vein aneurysm (9.2 x 9.0 cms). Primary repair of the AVF
      was done. A Doppler scan showed marked reduction in the size of the aneurysm, 4
      months after surgery. Cases associated with a venous aneurysm distant from the
      site of AVF are rare and there are only 7 cases reported in the international
      literature.

PMID- 22482390
TI  - Use of polyethylene glycol in children less than 3 years of age.
AB  - Chronic constipation is extremely common gastrointestinal problem in children.
      Polyethylene glycol (PEG) has been shown to be effective for both disimpaction
      and maintenance treatment in older children with chronic constipation. Literature
      review was carried out using Medline via PubMed (1950 to 2010), Cinahl (1982 -
      2010) and Embase (1974 to 2010) to evaluate the efficacy and safety of PEG in
      infants and children less than 3 years of age. There were no relevant reviews in
      the Cochrane Library. Only 5 relevant studies were found for children in the age
      group below 3 years. Pooled analysis of all the studies showed a statistically
      significant difference in the stool frequency before and after treatment with
      polyethylene glycol (p < 0.001). Although, limited published evidence to date
      supports its use in terms of safety and efficacy, larger randomized controlled
      trials are needed especially in young infants to substantiate the evidence.

PMID- 22482391
TI  - Diet and nutrition in liver disease patients.

PMID- 22482392
TI  - Current pattern of antibiotic resistance in Staphylococcus aureus clinical
      isolates and the emergence of vancomycin resistance.

PMID- 22482393
TI  - Perinephric drain - an unusual suspect of ureteral obstruction after open
      pyelolithotomy.

PMID- 22482394
TI  - Asking questions in the solution space: methodological issues in evaluating
      equity.
AB  - This paper presents an overview of some core methodological issues in improving
      the evaluation of health equity interventions. It argues that evaluation can play
      a central role in the solution space if it takes a futures orientation and
      develops adaptive approaches. It makes the case that purpose must drive method
      and that clarity in values is central. It suggests a process to rethink health
      equity interventions, reshape policy based on evaluation at the systems level,
      and reform evaluation of health equity so that it has the capacity to adapt and
      to more realistically reflect the dynamic and changing nature of systems.

PMID- 22482395
TI  - The kidney and hypertension: lessons from mouse models.
AB  - The pathogenesis of hypertension is multi-factorial, involving many of the
      systems contributing to blood pressure homeostasis including the vasculature,
      kidneys, central, and sympathetic nervous systems, along with various hormonal
      regulators. However, over the years, many studies have indicated a predominant
      importance of the kidney in blood pressure homeostasis and hypertension. This
      work has established the notion that the kidney is a key determinant of the
      chronic level of intra-arterial pressure playing a major role in the pathogenesis
      of hypertension. Therefore, this review will focus on recent work using
      genetically modified mouse models addressing the role of the kidney in
      hypertension. In particular, human genetic studies of Mendelian disorders with
      major impact on blood pressure homeostasis have provided powerful evidence for a
      role of the kidney in hypertension. Of the approximately 20 genes identified as
      causal in these disorders, virtually all have an effect on the control of solute
      transport in the kidney. As such, we have especially focused on generation of
      mouse models addressing the nature of these specific molecular defects in nephron
      function that produce an alteration in blood pressure.

PMID- 22482396
TI  - Range and distribution of NT-proBNP values in stable corrected congenital heart
      disease of various types.
AB  - BACKGROUND: Elevated levels of N-terminal pro-brain natriuretic peptide (NT
      proBNP) are an expected finding in many adults with congenital heart disease
      (ACHD) but no reports have described the range of values within different
      diagnostic groups. METHODS: Between the years 2003 and 2011 we measured NT-proBNP
      in consecutive ACHD patients attending the outpatient department. Further NT
      proBNP analysis was performed on 705 blood samples from 394 stable patients with
      the defect corrected. The results were compared among different diagnostic groups
      and with a control group of healthy volunteers. RESULTS: The median value of NT
      proBNP in the whole cohort was signifinatly higher than in the control group (211
      vs 42 pg/mL; P < 0.0001). The median value of NT-proBNP in pg/mL and the
      percentage of normal NT-proBNP values in the listed diagnostic groups were as
      follows: coarctation of the aorta (COA), 97 (64%); pulmonary stenosis (PS),160
      (48%); secundum atrial septal defect (ASD), 254 (44%); incomplete
      atrioventricular septal defect (AVSD), 211 (32%); ventricular septal defect
      (VSD), 154 (58%); tetralogy of Fallot (TOF), 177 (38%); transposition of the
      great arteries (TGA) after Mustard, 237 (20%) or Senning correction, 143 (39%);
      Ebstein anomaly 287, (26%); pulmonary atresia (PA), 327 (18%); and complex
      defects after Fontan procedure, 184 (31%). CONCLUSIONS: Normal levels of NT
      proBNP were found most often in patients after the correction of coarctation of
      the aorta and ventricular septal defect with the highest levels found in
      pulmonary atresia and Ebstein anomaly. Our results may serve as reference values
      for different ACHD groups.

PMID- 22482397
TI  - Genetics and hypertension: is it time to change my practice?
AB  - Recent advances in genotyping technology and in particular a number of large
      scale genome-wide association studies have helped to unravel the genetic basis of
      hypertension. Although our knowledge is still far from being complete it is
      important to ask how genetic findings could be translated to clinical practice.
      In a first step we summarize the strategies to dissect the genetics of
      hypertension from candidate gene studies to genome-wide association studies and
      recent sequencing experiments. The greatest hope in this context is the
      development of new drugs that are based on newly discovered pathophysiological
      principles. We describe examples where significant therapeutic effects are
      achieved with agents targeting pathways that contribute only small amounts to the
      genetic variability of a phenotype. There are good reasons to believe that new
      drugs will be developed based on genetic data in hypertension. We also highlight
      the potential for pharmacogenetics and risk stratification. The former is not
      currently supported by a larger body of evidence, but well designed studies are
      under way. The latter needs to follow the same principles for evaluation of other
      novel biomarkers of cardiovascular risk and is unlikely to influence clinical
      practice in the next few years.

PMID- 22482398
TI  - Structure-activity relationships of alpha-, beta(1)-, gamma-, and delta-tomatine
      and tomatidine against human breast (MDA-MB-231), gastric (KATO-III), and
      prostate (PC3) cancer cells.
AB  - Partial acid hydrolysis of the tetrasaccharide (lycotetraose) side chain of the
      tomato glycoalkaloid alpha-tomatine resulted in the formation of four products
      with three, two, one, and zero carbohydrate side chains, which were separated by
      high-performance liquid chromatography (HPLC) and identified by thin-layer
      chromatography (TLC) and liquid chromatography ion-trap time-of-flight mass
      spectrometry (LCMS-IT-TOF). The inhibitory activities in terms of IC(50) values
      (concentration that inhibits 50% of the cells under the test conditions) of the
      parent compound and the hydrolysates, isolated by preparative HPLC, against
      normal human liver and lung cells and human breast, gastric, and prostate cancer
      cells indicate that (a) the removal of sugars significantly reduced the
      concentration-dependent cell-inhibiting effects of the test compounds, (b) PC3
      prostate cancer cells were about 10 times more susceptible to inhibition by alpha
      tomatine than the breast and gastric cancer cells or the normal cells, (c) the
      activity of alpha-tomatine against the prostate cancer cells was 200 times
      greater than that of the aglycone tomatidine, and (d) the activity increased as
      the number of sugars on the aglycone increased, but this was only statistically
      significant at p < 0.05 for the normal lung Hel299 cell line. The effect of the
      alkaloids on tumor necrosis factor alpha (TNF-alpha) was measured in RAW264.7
      macrophage cells. There was a statistically significant negative correlation
      between the dosage of gamma- and alpha-tomatine and the level of TNF-alpha. alpha
      Tomatine was the most effective compound at reducing TNF-alpha. The dietary
      significance of the results and future research needs are discussed.

PMID- 22482399
TI  - [Inhibitory effect of lentiviral-mediated RNA on the expression of Foxp3 protein
      in melanoma cells].
AB  - AIM: To explore the feasibility of RNA interference in the treatment of melanoma
      by inhibiting the Foxp3 gene expression in mouse B16 melanoma cells using RNA
      interference (RNAi) in vitro. METHODS: Small interfering  RNA (siRNA) was
      designed according to Foxp3 gene. A short hairpin RNA (shRNA) lentivirus
      expression vector was constructed and   transfected into mouse B16 cells,  and
      RNA interference was induced in vitro. Western blot and real-time RT-PCR were
      performed  to detect the expression of Foxp3 gene. ELISA was applied to detect
      the changes of TGF-beta(1);,  TGF-beta(2);,  IL-10 and other cytokines. The B16
      cells after interference were co-cultured with CD4(+);CD25(-);T lymphocytes. CCK8
      assay was used to monitor the proliferation of CD4(+);CD25(-);T lymphocytes.
      RESULTS: shRNA could suppress the expression level of Foxp3, down-regulate the
      inhibitory ability of tumor cells on the proliferation of CD4(+);CD25(-);T
      lymphocytes,  and reduce the secretion of TGF-beta(1);, TGF-beta(2);,  IL-10 and
      other cytokines,  in particular the expression of TGF-beta(2);. CONCLUSION: RNA
      interference can inhibit the expression of target gene Foxp3 in mice melanoma
      cells and the proliferation of tumor cells. It can also reduce the inhibition on
      the proliferation of CD4(+);CD25(-);T lymphocytes,  and the secretion of
      inhibitory cytokines.

PMID- 22482400
TI  - [Establishment of a lung cancer A549 cell line stable over-expressing integrin
      linked kinase protein and its biological activity].
AB  - AIM: To establish a lung cancer A549 cell line stable over-expressing human
      integrin linked kinase (ILK) and study the effect of over-expression of ILK on
      biological activity of A549 cells. METHODS: Human ILK gene was amplified by RT
      PCR,  then cloned into pEGFP-C1 vector to construct pEGFP-ILK. After confirmed by
      restriction analysis and sequencing,  the recombinant plasmid was transfected
      into A549 cells mediated with liposome,  then G418-resistant clones of A549 cells
      (A549/pEGFP-ILK) as experimental group were obtained,  and paralleled with the
      vector control (A549/pEGFP-C1) and A549 cell control. The expression and
      localization of EGFP-ILK fusion protein in A549 cells was observed by
      fluorescence microscopy. RT-PCR and Western blot were performed to detect the
      level of ILK mRNA and ILK protein of each group cells respectively. The cell
      proliferation was tested by methylthiazolyl tetrazolium (MTT) assay,  and the
      cell apoptosis was measured by flow cytometry,  and the morphologic changes of
      cells were observed by HE staining. RESULTS: Both restriction analysis and
      sequencing proved that the pEGFP-ILK plasmid was constructed correctly. The
      distribution of fluorescence of stable transfected A549 cells indicated that the
      product of ILK gene was mainly located in cytoplasm. Compared with A549/pEGFP-C1
      group and A549 group,  the level of ILK mRNA and ILK protein of A549/pEGFP-ILK
      cells were significantly increased,  which over-expression ratio was 218.18% and
      245.45% respectively (P<0.05). The proliferation ability of the A549 cells over
      expressing ILK was increased significantly (P<0.05). However,  the apoptosis of
      A549/pEGFP-ILK cell was inhibited significantly by over-expression of ILK
      (P<0.05). After HE staining,  the increased mitosis were observed only in
      A549/pEGFP-ILK group cells. CONCLUSION: The lung cancer cell line stable over
      expressing ILK protein was constructed successfully,  and ILK over-expression
      could promote cell proliferation,  inhibit cell apoptosis and increase mitosis.

PMID- 22482401
TI  - [Overexpression of Smac gene enhanced chemotherapeutic sensitivity of esophageal
      cancer cell line Eca109 to cisplatin].
AB  - AIM: To investigate the effects of Smac gene overexpression on chemotherapeutic
      sensitivity of esophageal cancer cell line Eca109 to cisplatin. METHODS: pcDNA3.1
      Smac with GFP and pcDNA3.1-Smac with GFP were transfected into esophageal cancer
      cell line Eca109 by liposome and incubated with G418 for subclone selection.The
      efficiency of transfection was observed under fluorescence microscope, cellular
      Smac gene expression were determined  by  Western blot. Cisplatin treated group
      (1, 5, 10 mg/L) and cisplatin untreated group were selected to treat
      untransfected and transfected esophageal cancer cell line Eca109.   Apoptosis was
      determined by Annexin V/PI. RESULTS: The subclone esophageal cancer cell line
      Eca109,  stable expressing Smac+GFP and neo+GFP respectively,  were successfully
      selected,  named as Eca109/Smac,  Eca109/neo. Compared with the Eca109/neo and
      Eca109,  the Smac expression level of Eca109/Smac was significantly
      increased(P<0.05). In cisplatin untreated group,  the apoptosis rate was not
      associated with Smac expression. In cisplatin treated group (1, 5, 10 mg/L), 
      compared with Eca109/neo and Eca109,  the apoptosis rate of the Eca109/Smac was
      significantly increased after the treatments of cisplatin,  the difference were
      significant(P<0.05). In addition,  the apoptosis rate of Eca109/Smac was
      significantly increased with the concentration of cispaltin increased(P<0.05).
      The difference between Eca109/neo and Eca109 were not significant. CONCLUSION:
      Smac gene didn't induce apoptosis in the cisplatin untreated Eca109 cells. Smac
      gene overexpression could increase chemotherapeutic sensitivity of esophageal
      cancer cell line Eca109 to cisplatin.

PMID- 22482402
TI  - [Effects of TFDP3 on regulating the autophagy and apoptosis of LNCaP cells].
AB  - AIM: To investigate the effect of TFDP3 on prostate cancer cell line LNCaP by
      transgenic method, and to explore the effect of TFDP3 on regulating the autophay
      and apoptosis by co-regulation with E2F1. METHODS: LNCaP cells were transfected
      with pcDNA3.1-TFDP3, pCMV-E2F1-HA or pcDNA3.1 empty vector.The expression of
      TFDP3, E2F1 and LC3B were detected by real-time PCR after transfection for 24 h.
      Western blotting was used to monitor the changes in autophagy-associated protein
      LC3B, Apoptosis of transfected cells were analyzed by flow cytometry. RESULTS:
      The results showed that activation of TFDP3 upregulates the expression of
      autophagy genes-microtubule-associated protein-1 light chain-3B (LC3B), and E2F1
      antagonizes TFDP3-induced autophagy, and TFDP3 can inhibit E2F1-induced
      apoptosis. CONCLUSION: TFDP3 upregulates the expression of autophagy gene LC3B
      and inhibits E2F1-induced apoptosis, and may play an important role in prostate
      cancer.

PMID- 22482403
TI  - [Screening  for   genes associated with cardiac fibrosis induced by aldosterone].
AB  - AIM: To investigate differently expressed genes associated with cardiac fibrosis
      induced independently by aldosterone. METHODS: Fetal cardiac fibroblasts
      (FCFs)were isolated and cultured. Total RNA was extracted 8 hours after
      aldosterone administration. Then gene chips were used to screen these RNA
      samples. Some of candidate genes were confirmed by RT-PCR and Western blot.
      RESULTS: Differently expressed 1519 genes were screened. Up-regulated genes were
      714 while down-regulated  genes were 805. The expression of CCL7,  MMP-26 and
      IL31RA was tested by RT-PCR and western blot,  the results is identical with
      those by gene chips. CONCLUSION: Gene chip can efficiently single out differently
      expressed genes induced dependently by aldosterone in FCFs. CCL7,  MMP-26 and
      IL31RA may be associated with cardiac fibrosis induced by aldosterone.

PMID- 22482404
TI  - [Expression of MADD in lung adenocarcinoma tissues and its effects on
      proliferation and apoptosis of lung adenocarcinoma A549 cells].
AB  - AIM: To investigate the expression of MAPK-activating death domain protein (MADD)
      in lung adenocarcinoma tissues and its effects on proliferation and apoptosis of
      lung adenocarcinoma A549 cells. METHODS: Immunohistochemistry was used to detect
      the expression of MADD in lung normal and tumor tissues. The expression of IG20
      gene in A549 cells was measured by reverse transcription polymerase chain
      reaction. A549 cells were transfected with pEYFP-MADD plasmids carrying MADD gene
      or pNL-SIN-GFP-MID lentiviral vectors used for RNA interference.   MADD
      expression and cell proliferation and apoptosis were determined by Western blot,
      MTT assay, and flow cytometry. RESULTS: The expression levels of MADD were higher
      in lung adenocarcinoma and squamous cell carcinoma tissues than that in lung
      normal tissues, and lung adenocarcinoma tissues expressed more MADD than lung
      squamous cell carcinoma tissues. The transcript encoding MADD was expressed in
      A549 cells. The transfection of pEYFP-MADD plasmids could increase MADD
      expression  and cell    proliferation   of  A549 cells,   while the A549 cells
      transfected with pNL-SIN-GFP-MID lentiviral vectors showed significantly 
      decreases in the MADD level and proliferation. It is shown that MADD
      overexpression could inhibit A549 cell apoptosis, and knock down of MADD could
      promote apoptosis of them. CONCLUSION: The expression of MADD increases obviously
      in lung adenocarcinoma, and MADD can promote survival of lung adenocarcinoma
      cells by inhibiting apoptosis.

PMID- 22482405
TI  - [Co-stimulation  of multiple activating factors  on proliferation and phenotype
      of T lymphocytes in peripheral blood in vitro].
AB  - AIM: To observe the costimulation of multiple activating factors effects on the
      proliferation and phenotype of T lymphocytes in vitro. METHODS: Peripheral blood
      mononuclear cells (PBMCs) were separated by fractionation on Ficoll-Hypaque
      gradient. According to adding different cytokines (CD3 mAb, CD28 mAb, IFN-gamma,
      IL-1alpha, IL-2 and IL-15), the experiments were divided into seven groups.
      Effects of different cytokines on the proliferation of PBMC were counted by
      automated hematology analyzer five categories. The phenotypes (CD3, CD4, CD8,
      CD28, CD16, CD56(+);CD16, CD3(+);CD8(+);, CD3(+);CD4(+);, CD3(+); CD56(+);,
      CD45RO) expressing on the surface of costimulatory cells were detected by flow
      cytometry, and the cytotoxicity of costimulatory cells on SGC-7901, SW-1990 and
      SW-116 cell lines was examined by lactate dehydrogenase release method. RESULTS:
      The proliferation has significant difference when adding different cytokines into
      PBMCs culture system, the highestest proliferation multiples group is the one
      contains cytokines CD3, CD28, IFN-gamma, IL-2, IL-1alpha, IL-15 and IL-21, which
      proliferation multiple is 255.3+/-6.3 at the tenth day of cell culture, obviously
      higher than the other culture systems which only contains CD3, IFN-gamma and IL-2
      (166.6+/-5.5) (P<0.05). Part of cells'phenotype changed when adding different
      activating factors. Without IL-15, the proportion of CD16(+);CD56(+);(NK) cells
      and CD3(+);CD56(+); cells was higher than the other groups; CD45RO(+); memory
      cells is most evident when delayed adding IL-15 and IL-21 for three days. The
      cytotoxicity of PBMCs cultured for ten days with different activating factors had
      significant difference, the highest was the one which delayed adding IL-15 and IL
      21 for three days (76.2%, 60.3% and 70.6%, respectively.), higher than the cell
      culture groups containing CD3, IFN-gamma and IL-2 (54.9%, 44.6% and 50.4%,
      respectively) (P<0.05). The cultured cells had the strongest cytotoxicity on SGC
      7901 gastric adenocarcinoma cells. CONCLUSION: The PBMCs' proliferation,
      phenotype and cytotoxicity had significant difference after being activated by
      different stimulating factors, adding matching stimulating factors into the
      culture system have great value on cell-directed culture.

PMID- 22482406
TI  - [Biological behaviour of colon cancer cells transfected with  C-erbB2 shRNA
      plasmid].
AB  - AIM: To study the changes of the cell growth,  cell cycle distribution and cell
      apoptosis of colon cancer cell, HT-29, when C-erbB2 gene was knockdown by shRNA
      against C-erbB2. METHODS: Cell growth, cell cycle distribution and cell apoptosis
      were compared among three groups including plasmid experimental group(PEG),
      transfected reagent control group(TRCG)and negative plasmid control group(NPCG).
      Cell growth was measured by MTT assay. Cell cycle distribution and cell apoptosis
      were detected by flow cytometry. RESULTS: The inhibition rate of cell growth of
      PEG, TRCG and NPCG were 39.65%, 7.23% and 8.05%  respectively. The cell growth
      was significantly inhibited in PEG(P<0.01). The cells of G0/G1 phase were 74.93%,
      67.19%,  68.05%  respectively in PEG, TRCG and NPCG. The cells of G0/G1 phase in
      PEG were significantly more than those in TRCG and NPCG(P<0.05).While the cells
      of S phase were 7.81%, 14.02%, 13.70% in PEG, TRCG and NPCG respectively. The
      cells of S phase in PEG were significantly less than those in TRCG or
      NPCG(P<0.05).The cell apoptosis rate were 19.21%, 3.13%, 4.08% in PEG, TRCG and
      NPCG respectively. The cell apoptosis rate in PEG was significantly higher than
      those in TRCG or NPCG(P<0.01). CONCLUSION: Cell growth was inhibited by shRNA
      against C-erbB2 gene. Cell cycle was blocked in G0/G1 phase and apoptosis was
      induced by C-erbB2 shRNA. This indicates C-erbB2 gene plays important roles in
      the carcinogenesis and development of colon cancer.

PMID- 22482407
TI  - [Effects of anhydroicaritin on the immunologic function of mouse macrophages].
AB  - AIM: To investigate the effects of anhydroicaritin (AHI) on the immunologic
      function of mouse macrophages stimulated by lipopolysaccharide (LPS) in vitro and
      its related immunosuppressive mechanism. METHODS: Mouse bone marrow-derived
      macrophages were isolated. Then,  the drug toxicology of different concentrations
      of AHI on macrophages was measured by CCK-8 assay. The amount of NO produced in
      macrophages was detected by Griess kit. The phagocytosis of macrophages to E.coli
      BioParticles was assayed by flow cytometry (FCM). The expression of CD69,  which
      was the marker of early activation of macrophages,  was measured by FCM combined
      with two-color immunofluorescent staining of cell surface antigen. Cytometric
      bead array (CBA) kit was used to detect the production of cytokines of
      macrophages stimulated by LPS. RESULTS: AHI (2.5,   5,   10  MUmol/L)
      significantly reduced the production of NO in macrophages stimulated by LPS,  and
      inhibited the phagocytosis of activated macrophages. The results of FCM analysis
      showed that AHI decreased proportions of CD69 on LPS-stimulated macrophages.
      Furthermore,  AHI downregulated the secretion of cytokines of LPS-induced
      macrophages. CONCLUSION: AHI,  which exhibits immunosuppressive effect on the
      mouse macrophages stimulated by LPS,  is promising to be developed as an
      immunosuppressive reagent.

PMID- 22482408
TI  - [Effect of monocytes activated with lipopolysaccharide on human Th17 cell
      differentiation].
AB  - AIM: To investigate whether monocytes activated with lipopolysaccharide(LPS) have
      an effect on Th17 cell differentiation in humans, CD4(+) T cell and CD14(+)
      monocytes activated with LPS were treated in the absence or presence of anti-CD3
      mAb with various concentrations at different time points. METHODS: Purification
      of CD4(+) T cell and CD14(+) monocytes were performed by magnetic cell sorting
      and cultured together. Cultures were stimulated with LPS alone or anti-CD3 mAb
      alone or LPS plus anti-CD3 mAb for 3 days. In the anti-CD3 mAb stimulation cells
      were added different concentrations of LPS. Cells were activated under LPS/anti
      CD3 costimulation for 3, 6, or 10 days. The percentage of IL-17(+) T cells and
      INF-gamma(+) T was determined by flow cytometry. RESULTS: LPS or anti-CD3 mAb
      alone induced only very low levels of IL-17(+) T cells, (1.30 +/- 0.19)%, (1.10
      +/- 0.21)%, respectively. The percentage was substantially higher in the LPS and
      anti-CD3 mAb costimulationa as much as(2.01 +/- 0.46)%. In the presence of 0.1
      MUg/mL, 1 MUg/mL, 10 MUg/mL LPS, the proportion of Th17 reached to (1.92 +/-
      0.21)%, (1.30 +/- 0.37)%, (1.01 +/- 0.25)%. Low-concentration LPS (0.1 MUg/mL)
      stimulation favored Th17 differentiation. The highest proportion of IL-17(+) T
      cells was found at day 3(2.13 +/- 0.32)%, with levels declining at day 6 and day
      10, while, Th1 at day 6(17.45 +/- 3.04)%, declining at day 10. CONCLUSION: Low
      concentration LPS stimulation plus anti-CD3 mAb in short term support optimal
      Th17 generation. Nevertheless, this model closely mimics the environment of
      rheumatoid arthritis in vivo and proposes an effective model for the generation
      of human Th17 cells.

PMID- 22482409
TI  - [Construction and expression of the efficient recombinant plasmid pEE14.1-IFN
      alpha expressing human IFN-alpha].
AB  - AIM: To construct the eukaryotic expression plasmid pEE14.1-IFN-alpha expressing
      human IFN-alpha gene,  and to detect the expression of the plasmid in eukaryotic
      cells. METHODS: The human IFN-alpha gene amplified by  PCR  and   was linked into
      pCI-GPI,   then inserted into the eukaryotic expression vector pEE14.1. The
      recombinant plasmid was transfected into the 293T cells,    the  IFN-alpha  
      expression was detected by ELISA and Western blotting. RESULTS: Enzyme digestion
      and sequence analysis showed that the bicistronic eukaryotic expression vector
      pEE14.1-IFN-alpha was constructed successfully. The expression of plasmid was
      detected by ELISA,   and the production of IFN-alpha in supernatant of
      transfected cells was about 3.15 ng/mL. Also,    Western blotting could reveal
      the characteristic band of IFN-alpha gene. CONCLUSION: The vector is constructed
      successfully,   which provide a new selection for HBV immunotherapy.

PMID- 22482410
TI  - [Construction and  identification of human PRMT1 gene eukaryotic vector].
AB  - AIM: To construct the eukaryotic recombinant expression plasmid of pcDNA3.1(+)
      PRMT1. METHODS: Human PRMT1 cDNA was amplified by reverse transcription
      polymerase chain reaction (RT-PCR). After digested by BamH I, Hind III and
      ligation, PRMT1 was inserted into pcDNA3.1(+)eukaryotic expression vector. The
      positive colonies were screened and identified by PCR and sequencing. pcDNA3.1(+)
      PRMT1 plasmid was then transfected into the cultured A549 cell line with
      Lipofectamine(TM);2000. Realtime-PCR and Western blot were used to detect the
      mRNA and protein expression of PRMT1 respectively. RESULTS: The PRMT1 cDNA was
      successfully amplified, and pcDNA3.1(+)-PRMT1 were constructed. The inserted
      sequence in pcDNA3.1(+)-PRMT1 was the same as the sequence of PRMT1 cDNA
      published in NCBI GenBank. Further, Realtime PCR and Western blot results
      validated the recombinant plasmid expressed in A549 cell line efficiently.
      CONCLUSION: pcDNA3.1(+)-PRMT1 recombinant was successfully constructed.

PMID- 22482411
TI  - [Construction and identification of mouse wildtype-syndecan-1 and unshedding
      syndecan-1 expressing vector].
AB  - AIM: To construct the expressing vector pcDNA3.0- wildtype-syndecan-1(WT-sdc1)
      and pcDNA3.0-unshedding-syndecan-1(uS-sdc1), and to explore the expression in
      vitro. METHODS: (1)The mouse WT-sdc1 DNA was successfully amplified by PCR and
      then cloned into pcDNA3.0. uS-sdc1 was construct by Gene splicing by overlap
      extension- PCR on the basis of WT-sdc1. The two vectors confirmed by DNA
      sequencing. (2)there are 4 groups in our research: control group, pcDNA3.0
      transfected group, WT-sdc1 transfected group and uS-sdc1 transfected group. each
      vecter was transfected into IEC-6 cells by Lipofectamine(TM);2000. RT-PCR,
      Western blot and Dot blot were performed to detect the expression of syndecan-1
      before and after stimulation of phorbol 12-myristate 13-acetate (PMA) for 15 min.
      RESULTS: The vector WT-sdc1 and uS-sdc1 were successfully constructed although an
      non-sense mutation was in uS-sdc1. Compared to control and pcDNA3.0 transfected
      groups, WT-sdc1 and uS-sdc1 groups showed a significant increase in the
      expression of syndecan-1 in both mRNA and protein levels. In response to the
      stimulation of PMA, the expression of syndecan-1 was down-regulated at the
      protein levels but not mRNA levels. CONCLUSION: The WT-sdc1 and uS-sdc1 are
      successfully constructed, which lays the foundation for further studying of
      syndecan-1 in gastrointestinal inflammation.

PMID- 22482412
TI  - [Construction,  expression and characterization of the fusion gene of super
      antigen SEA and single chain Fv of the ND-1 monoclonal antibody against human
      colorectal cancer].
AB  - AIM: To construct  and express the recombinant ND-1-scFv/SEA,  a fusion protein
      of superantigen (staphylococcal enterotoxinA, SEA)  and single-chain variable
      fragment of monoclonal antibody ND-1 against human clolorectal carcinoma,  and to
      enhance the targeted killing effect of SEA. METHODS: The expression of the fusion
      protein was induced in E.coli M15 by IPTG. Ni-NTA resin affinity chromatography
      was used to separate and purify the expressed product. The specific binding
      activity of the purified ND-1-scFv/SEA protein was examined by indirect
      immunofluorescence assay and the targeted-cytotoxicity was determined using MTT
      assay. RESULTS: The expressing vector of fusion gene ND-1scFv/SEA was constructed
      successfully. ND-1-scFv/SEA protein retained a high binding affinity to antigen
      positive human colorectal cancer cell CCL-187 and had a stronger capability to
      activate PBMC and kill the target cells compared to SEA alone,  with a killing
      rate of 91% at 4  MUg/mL. CONCLUSION: ND-1-scFv/SEA fusion protein could
      specifically target colorectal cancer cell,  enhance the activity of kill tumor
      cell and has potential applications in the targeted therapy of colorectal cancer.

PMID- 22482413
TI  - [Humoral and cellular immune responses to HBV in the blood donors].
AB  - AIM: To study the magnitude and correlation of humoral and cellular immune
      responses to hepatitis surface antigen(HBsAg), preS1+S2 antigen, and core
      antigen(HBcAg) in the blood donors. METHODS: Enzyme linked immunosorbent assay
      (ELISA) was employed to scan the humoral immune responses to HBsAg, preS1+S2
      antigen, and HBcAg. Enzyme linked immunospot assay (ELISPOT) was used to check
      the antigen specific IFN-gamma secreting cells stimulated by HBsAg, preS1+S2
      antigen or HBcAg in peripheral blood mononuclear cell from blood donors. RESULTS:
      The prevalence of humoral immune response to preS1+S2 antigen was as high as
      85.7% (48/56), compared with the lower response to HBcAg (30.4%, 17/56). In the
      cellular immune response, there was no difference between preS1+S2 antigen and
      HBcAg, both of which were stronger than the response stimulated by HBsAg.
      PreS1+S2 antigen or HBsAg specific humoral immune and cellular immune responses
      were highly correlated, which could not be observed in the HBcAg specific humoral
      immune and cellular immune responses(P>0.05). CONCLUSION: Either humoral or
      cellular immune responses to HBsAg, preS1+S2 antigen and HBcAg could be detected
      in the blood donors. PreS1+S2 antigen immune responses, however, were most
      powerful, which may suggest that PreS1+S2 antigen may be a candidate for the
      further HBV vaccine.

PMID- 22482414
TI  - [Expression and clinical significance of CD3,  CD4 and COX-2 in non-small cell
      lung cancer].
AB  - AIM: To study expression and clinical significance of CD3,  CD4 and COX-2 in non
      small cell lung cancer (NSCLC). METHODS: Expression of COX-2,  CD3 and CD4 was
      detected by immunohistochemical staining in 37 cases of NSCLC. The correlation of
      CD3,  CD4,  COX-2 expressions and overall survival(OS)  was evaluated with
      spearman rank correlation analysis. RESULTS: The average surface density of CD3
      and the average optical density of CD4 were significantly associated with OS of
      NSCLC patients after surgery (P<0.05). However,  both two densities of COX-2 were
      correlated with survival time of patients (P>0.05). CONCLUSION: The expressions
      of CD3,  CD4 were significantly associated with OS of NSCLC patients.

PMID- 22482415
TI  - [Expression   and     significance    of CEACAM1 and HBx in HBV related
      hepatocellular carcinoma].
AB  - AIM: To investigate the expression and clinical significance of CEACAM1 and HBx
      in HBV related hepatocellular carcinoma. METHODS: The expression of CEACAM1 and
      HBx in 81 HBV related hepatocellular carcinoma were detected by
      immunohistochemistry,  and the relationship with clinicopathological features was
      analyzed. The expression of CEACAM1 in the human normal hepatocyte cell line QZG,
      HepG2 and HepG2-X were detected by Western blot. RESULTS: The positive rate of
      CEACAM1 and HBx in 81 HBV related hepatocellular carcinoma tissues were
      71.60%(58/81) and 74.07%(60/81) respectively. The expression of CEACAM1 and HBx
      were correlated with  portal vein invasion, nodal metastasis and TNM staging. The
      expression of CEACAM1 was negative correlated with HBx(r(s);=-0.310, P<0.01). 
      CEACAM1 protein was significantly down regulated in HepG2-X than in HepG2-PC and
      human normal hepatocyte cell line QZG. CONCLUSION: The higher expression of HBx
      and lower expression of CEACAM1  are  correlated with invasion and metastasis of
      HBV related hepatocelular carcinoma,  CEACAM1 may be a  effect  molecule in HBV
      related hepatocarcinogenesis.

PMID- 22482416
TI  - [Influence of IFN on expression of chemokine receptor CXCR1,  CXCR2 and their
      ligand IL-8 in the patients with chronic hepatitis B].
AB  - AIM: To study the mRNA levels of chemokine receptor CXCR1, CXCR2 and IL-8 in the
      patients with chronic hepatitis B and their association with IFN therapy.
      METHODS: The mRNA levels of CXCR1, CXCR2 and IL-8 in peripheral blood mononuclear
      cells(PBMC)of chronic hepatitis B patients were determined by real-time RT-PCR
      before and during the IFN-alpha therapy. RESULTS: The mRNA levels of CXCR1(0.4474
      +/- 0.0386)and IL-8(1.1897 +/- 0.1028)in peripheral blood of the patients with
      chronic hepatitis B were significantly higher than those in healthy
      donors(P<0.01). The mRNA level of CXCR2(0.4720 +/- 0.0458)was higher than those
      in healthy donors, but there was no significant differences between the two
      groups. During the treatment, the mRNA levels of CXCR1, CXCR2 and IL-8 obviously
      decreased. After treatment for six month, the mRNA level of CXCR1(0.4129 +/-
      0.0395), CXCR2(0.4461 +/- 0.0477) and IL-8(0.8660 +/- 0.1307)were significantly
      lower than those before treatment(P<0.01 or P<0.05). Additionally, the expressive
      levels of CXCR1, CXCR2 and IL-8 in the high HBV loading group(HBV-DNA>10(6);)were
      much higher than those in the low HBV loading group(HBV-DNA<10(6);). CONCLUSION:
      CXCR1 and IL-8 may contribute to hepatic inflammation. Among them, CXCR1, CXCR2
      and IL-8 decrease after IFN treatment, which illustrates that IFN-alpha plays an
      important role in down-regulating inflammation response, controlling the
      development of the patients' condition.

PMID- 22482417
TI  - [Changes and the clinical significance of CD4+ CD25+ regulatory T cells and Th17
      cells in peripheral blood of infants with respiratory syncytial virus
      bronchiolitis].
AB  - AIM: To observe the percentages of CD4(+);CD25(+); regulatory T cells (Tregs) and
      Th17 cells and the levels of IL-10, TGF-beta and IL-17 in peripheral blood of
      infants with respiratory syncytial virus (RSV) bronchiolitis. The relationship
      between above cells, cytokines and RSV bronchiolitis was determined. METHODS:
      Thirty-three infants with RSV bronchiolitis, twenty-eight infants with non-RSV
      pneumonia and twenty-six healthy infants were enrolled. The percentages of Tregs
      and Th17 cells in peripheral blood were detected by flow cytometer (FCM), and the
      levels of IL-10, TGF-beta and IL-17 in plasma were determined by ELISA. RESULTS:
      The percentage of Tregs and the levels of IL-10 and TGF-beta in infants with RSV
      bronchiolitis were significantly lower than those in infants with non-RSV
      pneumonia and healthy infants (P<0.05), while the percentage of Th17 cells and
      the level of IL-17 in infants with RSV bronchiolitis were significantly higher
      than those in infants with non-RSV pneumonia and healthy infants (P<0.05).
      CONCLUSION: The imbalance between Tregs and Th17 cells in peripheral blood of
      infants with RSV bronchiolitis may be one of the pathogenesis of RSV
      bronchiolitis.

PMID- 22482418
TI  - [Expression and clinical significance of PD-L1 on CD14+ monocyte in the
      peripheral blood of patients with systemic lupus erythematosus].
AB  - AIM: To detect expression of (programmed death ligand 1, PD-L1)on CD14(+)
      Monocyte(Mo)in the patients with systemic lupus erythematosus(SLE)and their
      clinical significance is analyzed. METHODS: The expression of PD-L1 on the
      CD14(+) Mo was examined in patients with 51 active SLE and 38 healthy
      controls(HC) by flow cytometry. The proportions of expression of PD-L1 on CD14(+)
      Mo were compared between not only inactive or active SLE patients and healthy
      controls(HC), but also between patients with lupus nephritis and without lupus
      nephritis. Correlation with clinical manifestations and laboratory findings was
      analyzed. RESULTS: The Proportions of CD14(+) PD-L1(+) Mo were significantly
      increased in active and inactive SLE patients as compared with HC(all P<0.05).
      The proportions of CD14(+) PD-L1(+) Mo in SLE patients with nephritis were
      significantly higher than those in patients without nephritis. A positive
      correlation was observed for proportions of CD14(+) PD-L1(+) Mo with SLEDAI
      score, and amounts of proteinuria. Proportions of CD14(+) PD-L1(+) Mo in SLE
      patients with anti-dsDNA, anti-Sm, anti-U1RNP and anti-nucleosome were higher
      than those in SLE patients without those antibody(P<0.05). CONCLUSION: The
      aberrations of proportions of CD14(+) PD-L1(+) Mo were observed in patients with
      SLE. Proportions of CD14(+) PD-L1(+) Mo were correlated with disease activity and
      production of antibody.

PMID- 22482419
TI  - Editorial: Anti Alzheimer agents.

PMID- 22482420
TI  - Inhibition of advanced glycation end product formation by Pu-erh tea ameliorates
      progression of experimental diabetic nephropathy.
AB  - Accumulation of advanced glycation end products (AGEs) has been implicated in the
      development of diabetic nephropathy. We investigated the effects of Pu-erh tea on
      AGE accumulation associated with diabetic nephropathy. Although it did not affect
      blood glucose levels and insulin sensitivy, Pu-erh tea treatment for 8 weeks
      attenuated the increases in urinary albumin, serum creatinine, and mesangial
      matrix in db/db mice. We found that Pu-erh tea prevented diabetes-induced
      accumulation of AGEs and led to a decreased level of receptor for AGE expression
      in glomeruli. Both production and clearance of carbonyl compounds, the main
      precursor of AGE formation, were probably attenuated by Pu-erh tea in vivo
      independent of glyoxalase I expression. In vitro, HPLC assay demonstrated Pu-erh
      tea could trap methylglyoxal in a dose-dependent manner. Our study raises the
      possibility that inhibition of AGE formation by carbonyl trapping is a promising
      approach to prevent or arrest the progression of diabetic complications.

PMID- 22482421
TI  - Microsurgical management of glomus spinal arteriovenous malformations: pial
      resection technique: Clinical article.
AB  - OBJECT: Intramedullary, or glomus, spinal arteriovenous malformations (AVMs) are
      rare vascular lesions amenable to resection with or without adjuvant
      embolization. The authors retrospectively reviewed the senior author's (R.F.S.'s)
      surgical series of intramedullary spinal AVMs to evaluate clinical and
      radiographic outcomes. METHODS: Detailed chart and radiographic reviews were
      performed for all patients with intramedullary spinal AVMs who underwent surgical
      treatment between 1994 and 2011. Presenting and follow-up neurological
      examination results were obtained and graded using the modified Rankin Scale
      (mRS) and McCormick Scale. Surgical technique, outcomes, complications, and long
      term angiographic studies were reviewed. RESULTS: During the study period, 20
      patients (10 males and 10 females) underwent resection of glomus spinal AVMs. The
      mean age at presentation was 30 +/- 17 years (range 7-62 years). The location of
      the AVMs was as follows: cervical spine (n = 10), thoracic spine (n = 9), and
      cervicothoracic junction (n = 1). The most common presenting signs and symptoms
      included paresis or paralysis (65%), paresthesias (40%), and myelopathy (40%).
      Perioperative embolization was performed in the majority (60%) of patients. Pial
      AVM resection was performed in 17 cases (85%). Angiographically verified AVM
      obliteration was achieved in 15 patients (75%). At a mean follow-up duration of
      45.4 +/- 52.4 months (range 2-176 months), 14 patients (70%) remained
      functionally independent (mRS and McCormick Scale scores <= 2). One perioperative
      complication occurred, yielding a surgical morbidity rate of 5%. Three
      symptomatic spinal cord tetherings occurred at a mean of 5.7 years after AVM
      resection. No neurological decline was observed after endovascular and surgical
      interventions. No deaths occurred. Long-term angiographic follow-up data were
      available for 9 patients (40%) at a mean of 67.6 +/- 60.3 months (range 5-176
      months) following AVM resection. Durable AVM obliteration was documented in 5
      (83%) of 6 patients. CONCLUSIONS: Intramedullary AVMs may be safely resected with
      satisfactory clinical and angiographic results. The pial resection technique,
      which provides subtotal AVM nidus resection, effectively devascularized these
      lesions, as confirmed on postoperative angiography, without violating the spinal
      cord parenchyma, thereby potentially reducing iatrogenic injury.

PMID- 22482422
TI  - Editorial: Load-sharing score.

PMID- 22482423
TI  - Does the load-sharing classification predict ligamentous injury, neurological
      injury, and the need for surgery in patients with thoracolumbar burst fractures?:
      Clinical article.
AB  - OBJECT: The load-sharing score (LSS) of vertebral body comminution is predictive
      of results after short-segment posterior instrumentation of thoracolumbar burst
      fractures. Some authors have posited that an LSS > 6 is predictive of
      neurological injury, ligamentous injury, and the need for surgical intervention.
      However, the authors of the present study hypothesized that the LSS does not
      predict ligamentous or neurological injury. METHODS: The prospectively collected
      spinal cord injury database from a single institution was queried for
      thoracolumbar burst fractures. Study inclusion criteria were acute (< 24 hours)
      burst fractures between T-10 and L-2 with preoperative CT and MRI. Flexion
      distraction injuries and pathological fractures were excluded. Four experienced
      spine surgeons determined the LSS and posterior ligamentous complex (PLC)
      integrity. Neurological status was assessed from a review of the medical records.
      RESULTS: Forty-four patients were included in the study. There were 4 patients
      for whom all observers assigned an LSS > 6, recommending operative treatment.
      Eleven patients had LSSs <= 6 across all observers, suggesting that nonoperative
      treatment would be appropriate. There was moderate interobserver agreement (0.43)
      for the overall LSS and fair agreement (0.24) for an LSS > 6. Correlations
      between the LSS and the PLC score averaged 0.18 across all observers (range -0.02
      to 0.34, p value range 0.02-0.89). Correlations between the LSS and the American
      Spinal Injury Association motor score averaged -0.12 across all observers (range 
      0.25 to -0.03, p value range 0.1-0.87). Correlations describing the relationship
      between an LSS > 6 and the treating physician's decision to operate averaged 0.17
      across all observers (range 0.11-0.24, p value range 0.12-0.47). CONCLUSIONS: The
      LSS does not uniformly correlate with the PLC injury, neurological status, or
      empirical clinical decision making. The LSSs of only one observer correlated
      significantly with PLC injury. There were no significant correlations between the
      LSS as determined by any observer and neurological status or clinical decision
      making.

PMID- 22482425
TI  - Monomeric platinum(II) hydroxides supported by sterically dominant alpha-diimine
      ligands.
AB  - The use of two new highly sterically bulky alpha-diimine ligands for the
      stabilization of neutral, monomeric platinum(II) hydroxo complexes is described.
      Halide abstraction from LPtCl(2) complexes of these ligands in the presence of
      water, followed by deprotonation of the cationic aquo complex, leads to LPt(OH)Cl
      and LPt(OH)(2). The latter can be reprotonated with HNTf(2) to yield a highly
      fluxional hydroxoaquoplatinum(II) cation.

PMID- 22482426
TI  - Carbon nanotube field-effect transistors for use as pass transistors in
      integrated logic gates and full subtractor circuits.
AB  - The use of carbon nanotube (CNT)-based field-effect transistors (FETs) as pass
      transistors is investigated. Logic gates are designed and constructed with these
      CNT FETs in the pass-transistor logic (PTL) style. Because two of the three
      terminals of every CNT FET are used as inputs, the efficiency per transistor in
      PTL circuits is significantly improved. With the PTL style, a single pair of
      FETS, one n-type and one p-type, is sufficient to construct high-performance AND
      or OR gates in which the measured output voltages are consistent with those
      quantitatively derived using the characteristics of the pair of the constituent n
      and p-FETs. A one-bit full subtractor, which requires a total of 28 FETs to
      construct in the usual CMOS circuit, is realized on individual CNTs for the first
      time using the PTL style with only three pairs of n- and p-FETs.

PMID- 22482424
TI  - The anticancer effects of resveratrol: modulation of transcription factors.
AB  - Resveratrol (3, 4', 5-trihydroxystilbene), a naturally occurring phytoalexin
      readily available in the diet, is reported to possess both chemopreventive and
      chemotherapeutic activities in several cancers. However, despite the
      identification of numerous molecular targets, the underlying mechanisms involved
      in the anticancer activities of resveratrol are not completely understood.
      Resveratrol is postulated to function as a potential signaling pathway modulator
      and, as such, is demonstrated to affect a multitude of signal transduction
      pathways associated with tumorigenesis and/or carcinogenesis; it is likely that
      this collective activity, rather than just a single effect, may play an important
      role in the anticancer properties of resveratrol. Since transcription factors
      control the expression of many genes, the elucidation of molecular targets of
      resveratrol involved in transcriptional regulation is necessary to better
      understand how this dietary phytochemical affects chemopreventive and
      chemotherapeutic processes. As a result, investigators have increasingly searched
      for and examined possible targets of resveratrol. In this review, we summarize
      the current knowledge on molecular targets, specifically transcription factors,
      that contribute to the observed anticancer effects of resveratrol related to 1)
      inhibition of carcinogenic activation and induction of carcinogen detoxification,
      2) induction of growth arrest and apoptosis, and 3) suppression of
      proinflammatory signaling pathways related to cancer progression.

PMID- 22482427
TI  - Zn(II) binding and DNA binding properties of ligand-substituted CXHH-type zinc
      finger proteins.
AB  - CCHH-type zinc fingers are among the most common DNA binding motifs found in
      eukaryotes. In a previous report, we substituted the second ligand cysteine
      residue with aspartic acid, producing a Zn(II)-responsive transcription factor;
      this indicates that a ligand substitution is a possible design target of an
      engineered zinc finger peptide. Despite the importance of Zn(II) binding with
      respect to the folding and DNA binding properties of a zinc finger peptide, no
      study about the effects of ligand substitution on both Zn(II) binding and DNA
      binding properties has been reported. Here, we substituted a conserved cysteine
      (C) with other zinc-coordinated amino acid residues, histidine (H), aspartic acid
      (D), and glutamic acid (E), to create CXHH-type zinc finger peptides (X = C, H,
      D, and E). The Zn(II)-dependent conformational change was observed in all
      peptides; however, the Zn(II) binding affinity and metal coordination geometry of
      the peptides were different. Gel mobility shift assays showed that the Zn(II)
      bound forms of the ligand-substituted derivatives retain DNA binding ability,
      while the DNA binding affinity decreased in the following manner: CCHH > CDHH >
      CEHH ? CHHH. The DNA binding sequence preferences of the ligand-substituted
      derivatives were similar to that of the wild type in the context of the full
      three-finger DNA-binding domain of transcription factor Zif268. These results
      indicate that artificial zinc finger proteins with various DNA binding affinities
      that respond to a diverse range of Zn(II) concentrations can be designed by
      substituting the Zn(II) ligand.

PMID- 22482428
TI  - Combining Fourier transform-ion cyclotron resonance/mass spectrometry analysis
      and Kendrick plots for silicon speciation and molecular characterization in
      petroleum products at trace levels.
AB  - A new method combining FT-ICR/MS analysis and Kendrick plots for the
      characterization of silicon species at trace levels in light petroleum products
      is presented. The method provides efficient instrumental detection limits ranging
      from 80 ng/kg to 5 MUg/kg and reliable mass accuracy lower than 0.50 ppm for
      model silicon molecules in spiked gasoline. More than 3000 peaks could be
      detected in the m/z 50-500 range depending on the nature of the gasoline sample
      analyzed. An in-house software program was used to calculate Kendrick plots.
      Then, an algorithm searched, selected, and represented silicon species classes
      (O(2)Si, O(3)Si, and O(4)Si classes) in Kendrick plots by incorporating model
      molecules' information (i.e., exact mass and intensity). This procedure allowed
      the complete characterization of more than 50 new silicon species with different
      degrees of unsaturation in petroleum products.

PMID- 22482429
TI  - Chemistry and biology of acylfulvenes: sesquiterpene-derived antitumor agents.

PMID- 22482430
TI  - Rotaxanes and biofunctionalized pseudorotaxanes via thiol-maleimide click
      chemistry.
AB  - Base-catalyzed thiol-maleimide click chemistry has been applied to the synthesis
      of neutral donor-acceptor [2]rotaxanes in good yield. This method is extended
      further to the synthesis of a glutathione-functionalized [2]pseudorotaxane, a
      precursor to integrated conjugates of interlocked molecules with proteins and
      enzymes.

PMID- 22482431
TI  - A set of molecular models for alkaline-earth cations in aqueous solution.
AB  - New Lennard-Jones plus point charge models are developed for alkaline-earth
      cations. The cation parameters are adjusted to the reduced liquid solution
      density of aqueous alkaline-earth halide salt solutions at a temperature of
      293.15 K and a pressure of 1 bar. This strategy is analogous to the one that was
      recently used for developing models for alkali and halide ions so that both model
      families are compatible. The force fields yield the reduced liquid solution
      density of aqueous alkaline-earth halide solutions in good agreement with
      experimental data over a wide range of salinity. Structural microscopic
      properties (i.e. radial distribution function and hydration number) are predicted
      in good agreement with experimental and quantum chemical data. The same holds for
      dynamic properties (i.e., hydration dynamics, self-diffusion coefficient and
      electric conductivity). Finally, the enthalpy of hydration of the salts in
      aqueous solution was favorably assessed.

PMID- 22482432
TI  - Bioactive carbazole alkaloids from Clausena wallichii roots.
AB  - Four new carbazole alkaloids, clausenawallines C-F (1-4), along with 18 known
      compounds (5-22) were isolated from the roots of Clausena wallichii. Compounds 3,
      9, and 22 exhibited significant antibacterial activity against methicillin
      resistant Staphylococcus aureus SK1 (MRSA SK1) and Staph. aureus TISTR 1466 with
      MIC values in the range 4-16 MUg/mL, whereas compound 4 showed the highest
      cytotoxicity against oral cavity cancer (KB) and small-cell lung cancer (NCI
      H187) with IC(50) values of 10.2 and 4.5 MUM, respectively.

PMID- 22482433
TI  - Virtual symposium 2.0.

PMID- 22482436
TI  - Profile of Bill Jack. Interviewed by Kristie Nybo.

PMID- 22482437
TI  - Go cell, go!

PMID- 22482438
TI  - DNase-treated RNA.

PMID- 22482439
TI  - Quantitative analysis of microRNAs in tissue microarrays by in situ
      hybridization.
AB  - MicroRNAs (miRNAs) have emerged as key regulators in the pathogenesis of cancers
      where they can act as either oncogenes or tumor suppressors. Most miRNA
      measurement methods require total RNA extracts which lack critical spatial
      information and present challenges for standardization. We have developed and
      validated a method for the quantitative analysis of miRNA expression by in situ
      hybridization (ISH) allowing for the direct assessment of tumor epithelial
      expression of miRNAs. This co-localization based approach (called qISH) utilizes
      DAPI and cytokeratin immunofluorescence to establish subcellular compartments in
      the tumor epithelia, then multiplexed with the miRNA ISH, allows for quantitative
      measurement of miRNA expression within these compartments. We use this approach
      to assess miR-21, miR-92a, miR-34a, and miR-221 expression in 473 breast cancer
      specimens on tissue microarrays. We found that miR-221 levels are prognostic in
      breast cancer illustrating the high-throughput method and confirming that miRNAs
      can be valuable biomarkers in cancer. Furthermore, in applying this method we
      found that the inverse relationship between miRNAs and proposed target proteins
      is difficult to discern in large population cohorts. Our method demonstrates an
      approach for large cohort, tissue microarray-based assessment of miRNA
      expression.

PMID- 22482440
TI  - Presence and removal of a contaminating NADH oxidation activity in recombinant
      maltose-binding protein fusion proteins expressed in Escherichia coli.
AB  - We observed the presence of contaminating NADH oxidation activity in maltose
      binding protein (MBP) fusion proteins expressed in Escherichia coli and purified
      using conventional amylose resin-based affinity chromatography. This
      contaminating NADH oxidation activity was detectable with at least four different
      enzymes from Cryptosporidium parvum expressed as MBP-fusion proteins (i.e., an
      enoyl-reductase domain from a type I fatty acid synthase, a fatty acyl-CoA
      binding protein, the acyl-ligase domain from a polyketide synthase, and a
      putative thioesterase), regardless of their NADH dependence. However,
      contaminating NADH oxidation activity was not present when fusion proteins were
      engineered to contain a His-tag and were purified using a Ni-NTA resin-based
      protocol. Alternatively, for proteins containing only an MBP-tag, the
      contaminating activity could be eliminated through the addition of 0.1% Triton X
      100 and 2% glycerol to the column buffer during homogenization of bacteria and
      first column wash, followed by an additional wash and elution with regular column
      and elution buffers. Removal of the artifactual activity is very valuable in the
      study of enzymes using NADH as a cofactor, particularly when the native activity
      is low or the recombinant proteins are inactive.

PMID- 22482441
TI  - Construction of effective inverted repeat silencing constructs using sodium
      bisulfite treatment coupled with strand-specific PCR.
AB  - RNA silencing has been exploited to produce transgenic plants with resistance to
      viral pathogens via posttranscriptional gene silencing (PTGS). In some cases,
      this technology is difficult to apply due to the instability of inverted repeat
      (IR) constructs during cloning and plant transformation. Although such constructs
      have been shown to be stabilized with introns and efficiently induce RNA
      silencing, we found that the Pdk intron did not stabilize South African cassava
      mosaic virus (SACMV) silencing constructs. Therefore, we developed a method for
      producing long SACMV IR constructs through bisulfite-induced base pair mismatches
      on the sense arm prior to IR assembly. Expression of SACMV BC1 mismatched IR
      constructs in the model test plant Nicotiana benthamiana resulted in a reduction
      in viral BC1 transcript levels, hence viral replication, upon SACMV infection.
      Mismatched SACMV AC1 IR constructs induced PTGS more efficiently in a N.
      benthamiana callus system than nonmismatched IR constructs. Our novel method for
      IR construct generation should be applicable to many sequences where the
      generation of these constructs has proven difficult in the past.

PMID- 22482442
TI  - Technique for strand-specific gene-expression analysis and monitoring of primer
      independent cDNA synthesis in reverse transcription.
AB  - Primer-independent cDNA synthesis during reverse transcription hinders
      quantitative analysis of bidirectional mRNA synthesis in eukaryotes as well as in
      cells infected with RNA viruses. We report a simple RT-PCR-based assay for strand
      specific gene-expression analysis. By modifying the cDNA sequence during reverse
      transcription, the opposite strands of target sequences can be simultaneously
      detected by postamplification melting curve analysis and primer-initiated
      transcripts are readily distinguished from nonspecifically primed cDNA. We have
      utilized this technique to optimize the specificity of reverse transcription on a
      panel of 15 target genes. Primer-independent reverse transcription occurred for
      all target sequences when reverse transcription was performed at 42 degrees C and
      accounted for 11%-57% of the final PCR amplification products. By raising the
      reaction temperature to 55 degrees C, the specificity of reverse transcription
      could be increased without significant loss of sensitivity. We have also
      demonstrated the utility of this technique for analysis of (+) and (-) RNA
      synthesis of influenza A virus in infected cells. Thus, this technique represents
      a powerful tool for analysis of bidirectional RNA synthesis.

PMID- 22482443
TI  - Hepatitis C genotype 1a replicon improved through introduction of fitness
      mutations.
AB  - The use of subgenomic replicon systems has long been a valuable screening tool
      for the discovery of small molecule antivirals against Hepatitis C virus. While
      genotype 1a replicon systems have been widely used in stable systems, use in
      transient assays has been hampered by low signal. Here we describe the generation
      of a more robust genotype 1a (H77) replicon through the introduction of two
      fitness mutations, NS4A-K1691R and NS4B-E1726G, for use in transient
      transfections. While these mutations significantly improved the signal to noise
      ratio, leading to more robust data, they have no effect on the potency of tool
      compounds against various targets of HCV, thereby making this new system a
      powerful tool for screening of compounds against the genotype 1a replicon.

PMID- 22482444
TI  - Changes in dark chocolate volatiles during storage.
AB  - Chocolate storage is critical to the quality of the final product. Inadequate
      storage, especially with temperature fluctuations, may lead to a change in
      crystal structure, which may eventually cause fat bloom. Bloom is the main cause
      of quality loss in the chocolate industry. The impact of various storage
      conditions on the flavor quality of dark chocolate was determined. Dark chocolate
      was stored in different conditions leading to either fat or sugar bloom and
      analyzed at 0, 4, and 8 weeks of storage. Changes in chocolate flavor were
      determined by volatile analysis and descriptive sensory evaluation. Results were
      analyzed by analysis of variance (ANOVA), cluster analysis, principal component
      analysis (PCA), and linear partial least-squares regression analysis (PLS).
      Volatile concentration and loss were significantly affected by storage
      conditions. Chocolates stored at high temperature were the most visually and
      texturally compromised, but volatile concentrations were affected the least,
      whereas samples stored at ambient, frozen, and high relative humidity conditions
      had significant volatile loss during storage. It was determined that high
      temperature storage caused a change in crystal state due to the polymorphic shift
      to form VI, leading to an increase in sample hardness. Decreased solid fat
      content (SFC) during high-temperature storage increased instrumentally determined
      volatile retention, although no difference was detected in chocolate flavor
      during sensory analysis, possibly due to instrumental and sensory sampling
      techniques. When all instrumental and sensory data had been taken into account,
      the storage condition that had the least impact on texture, surface roughness,
      grain size, lipid polymorphism, fat bloom formation, volatile concentrations, and
      sensory attributes was storage at constant temperature and 75% relative humidity.

PMID- 22482445
TI  - Synthesis and structures of cuprous triptycylthiolate complexes.
AB  - A synthesis of 1-(thioacetyl)triptycene (5), a convenient protected form of 1
      (thiolato)triptycene [STrip](-), is described, a key transformation being the
      high yield conversion of tert-butyl 1-triptycenyl sulfide (8) to 5 by a protocol
      employing BBr(3)/AcCl. Syntheses of the two-coordinate copper(I) compounds
      [Bu(4)N][Cu(STrip)(2)], [Bu(4)N]10, and [(Cu(IMes)(STrip)] (13) proceed readily
      by chloride displacement from CuCl and [Cu(IMes)Cl], respectively. Reaction of 10
      with Ph(3)SiSH or Me(3)SiI produces the heteroleptic species
      [Cu(STrip)(SSiPh(3))](-) (11) and [Cu(STrip)I](-) (12), detected by mass
      spectrometry, in mixture with the homoleptic bis(thiolate) anions. Structural
      identification by X-ray crystallography of the ligand precursor molecules 9
      (thioacetyl)anthracene (4, triclinic and orthorhombic polymorphs), tert-butyl 9
      anthracenyl sulfide (7), 5, and tert-butyl 1-triptycenyl sulfide (8) are
      presented. Crystallographic characterization of bis(9-anthracenyl)sulfide (3),
      which features a C-S-C angle of 104.0 degrees  and twist angle of 54.8 degrees 
      between anthracenyl planes, is also given. A crystal structure of
      [Bu(4)N][(STrip)], [Bu(4)N]9, provides an experimental measure of 144.6 degrees 
      for the ligand cone angle. The crystal structures of [Bu(4)N]10 and 13 are
      reported, the former of which reveals an unexpectedly small C-S...S-C torsion
      angle of ~41 degrees  (average of two values), which confers a near "cis"
      disposition of the triptycenyl groups with respect the S-Cu-S axis. This
      conformation is governed by interligand pi...pi and CH...pi interactions. A
      crystal structure of an adventitious product, [Bu(4)N][(Cu-STrip)(6)(MU(6)
      Br)].[Bu(4)N][PF(6)], [Bu(4)N]14.[Bu(4)N][PF(6)] is described, which reveals a
      cyclic hexameric structure previously unobserved in cuprous thiolate chemistry.
      The Cu(6)S(6) ring displays a centrosymmetric cyclohexane chair type conformation
      with a Br(-) ion residing at the inversion center and held in place by apparent
      soft-soft interactions with the Cu(I) ions.

PMID- 22482446
TI  - Pathologic lesions in neurodegenerative diseases.
AB  - This chapter will discuss two of the most widely used approaches to assessing
      brain structure: neuroimaging and neuropathology. Whereas neuropathologic
      approaches to studying the central nervous system have been utilized for many
      decades and have provided insights into morphologic correlates of dementia for
      over 100 years, accurate structural imaging techniques "blossomed" with the
      development and refinement of computerized tomographic scanning and magnetic
      resonance imaging (MRI), beginning in the late 1970s. As Alzheimer disease
      progresses over time, there is progressive atrophy of the hippocampus and
      neocortex--this can be quantified and regional accentuation of the atrophy can be
      evaluated using quantitative MRI scanning. Furthermore, ligands for amyloid
      proteins have recently been developed--these can be used in positron emission
      tomography studies to localize amyloid proteins, and (in theory) study the
      dynamics of their deposition (and clearance) within the brain over time.
      Neuropathologic studies of the brain, using highly specific antibodies, can
      demonstrate synapse loss and the deposition of proteins important in AD
      progression--specifically ABeta and phosphor-tau. Finally, neuropathologic
      assessment of (autopsy) brain specimens can provide important correlation with
      sophisticated neuroimaging techniques.

PMID- 22482447
TI  - Cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy (CAA) is cerebrovascular amyloid deposition. It is
      classified into several types according to the cerebrovascular amyloid proteins
      involved [amyloid beta-protein (Abeta), cystatin C (ACys), prion protein (APrP),
      transthyretin (ATTR), gelsolin (AGel), ABri/ADan, and AL]. Sporadic Abeta-type
      CAA is commonly found in elderly individuals and patients with Alzheimer's
      disease (AD). CAA-related disorders include hemorrhagic and ischemic brain
      lesions and dementia. It has been proposed that cerebrovascular Abeta originates
      mainly from the brain and is transported to the vascular wall through a
      perivascular drainage pathway, where it polymerizes into fibrils on vascular
      basement membrane through interactions with extracellular components. CAA would
      be promoted by overproduction of Abeta40 (a major molecular species of
      cerebrovascular Abeta), a decrease of Abeta degradation, or reduction of Abeta
      clearance due to impairment of perivascular drainage pathway. Further
      understanding of the molecular pathogenesis of CAA would lead to development of
      disease-modifying therapies for CAA and CAA-related disorders.

PMID- 22482448
TI  - The genetics of Alzheimer's disease.
AB  - Genetic factors play a major role in determining a person's risk to develop
      Alzheimer's disease (AD). Rare mutations transmitted in a Mendelian fashion
      within affected families, for example, APP, PSEN1, and PSEN2, cause AD. In the
      absence of mutations in these genes, disease risk is largely determined by common
      polymorphisms that, in concert with each other and nongenetic risk factors,
      modestly impact risk for AD (e.g., the epsilon4-allele in APOE). Recent genome
      wide screening approaches have revealed several additional AD susceptibility loci
      and more are likely to be discovered over the coming years. In this chapter, we
      review the current state of AD genetics research with a particular focus on loci
      that now can be considered established disease genes. In addition to reviewing
      the potential pathogenic relevance of these genes, we provide an outlook into the
      future of AD genetics research based on recent advances in high-throughput
      sequencing technologies.

PMID- 22482449
TI  - Alzheimer's disease and the amyloid beta-protein.
AB  - Alzheimer's disease is a devastating disorder that is estimated to affect more
      than 25 million people worldwide and for which there are no preventive, disease
      modifying, or curative therapies. Substantial evidence indicates that the amyloid
      beta-protein (Abeta) is a seminal factor in disease causation and may be a
      tractable therapeutic target. The ability of Abeta to self-associate to form
      oligomeric assemblies appears to underlie the early toxic events that lead to
      memory impairment and subsequent neurodegeneration. We review here research on
      Abeta folding, self-assembly, and toxicity, highlighting areas critical for the
      development of efficacious Abeta-directed therapeutics.

PMID- 22482450
TI  - Molecular insights into Parkinson's disease.
AB  - Mutations in SNCA, PINK1, parkin, and DJ-1 are associated with autosomal-dominant
      or autosomal-recessive forms of Parkinson's disease (PD), the second most common
      neurodegenerative disorder. Studies on the structural and functional properties
      of the corresponding gene products have provided significant insights into the
      molecular underpinnings of familial PD and the much more common sporadic forms of
      the disease. Here, we review recent advances in our understanding of four PD
      related gene products: alpha-synuclein, parkin, PINK1, and DJ-1. In Part 1, we
      review new insights into the role of alpha-synuclein in PD. In Part 2, we
      summarize the latest developments in understanding the role of mitochondrial
      dysfunction in PD, emphasizing the role of the PINK1/parkin pathway in regulating
      mitochondrial dynamics and mitophagy. The role of DJ-1 is also discussed. In Part
      3, we point out converging pathways and future directions.

PMID- 22482451
TI  - Huntington disease and the huntingtin protein.
AB  - Huntington disease (HD) is a devastating neurodegenerative disease that derives
      from CAG repeat expansion in the huntingtin gene. The clinical syndrome consists
      of progressive personality changes, movement disorder, and dementia and can
      develop in children and adults. The huntingtin protein is required for human
      development and normal brain function. It is subject to posttranslational
      modification, and some events, such as phosphorylation, can play an enormous role
      in regulating toxicity of the huntingtin protein. The function of huntingtin in
      the cell is unknown, and it may play a role as a scaffold. Multiple mouse models
      of HD have now been created with fragments and full-length protein. The models
      show variable fidelity to the disease in terms of genetics, pathology, and rates
      of progression. Pathogenesis of HD involves cleavage of the protein and is
      associated with neuronal accumulation of aggregated forms. The potential
      mechanisms of neurodegeneration are myriad, including primary effects of protein
      homeostasis, gene expression, and mitochondrial dysfunction. Specific therapeutic
      approaches are similarly varied and include efforts to reduce huntingtin gene
      expression, protein accumulation, and protein aggregation.

PMID- 22482454
TI  - Membrane pores in the pathogenesis of neurodegenerative disease.
AB  - The neurodegenerative diseases described in this volume, as well as many
      nonneurodegenerative diseases, are characterized by deposits known as amyloid.
      Amyloid has long been associated with these various diseases as a pathological
      marker and has been implicated directly in the molecular pathogenesis of disease.
      However, increasing evidence suggests that these proteinaceous Congo red staining
      deposits may not be toxic or destructive of tissue. Recent studies strongly
      implicate smaller aggregates of amyloid proteins as the toxic species underlying
      these neurodegenerative diseases. Despite the outward obvious differences among
      these clinical syndromes, there are some striking similarities in their molecular
      pathologies. These include dysregulation of intracellular calcium levels,
      impairment of mitochondrial function, and the ability of virtually all amyloid
      peptides to form ion-permeable pores in lipid membranes. Pore formation is
      enhanced by environmental factors that promote protein aggregation and is
      inhibited by agents, such as Congo red, which prevent aggregation. Remarkably,
      the pores formed by a variety of amyloid peptides from neurodegenerative and
      other diseases share a common set of physiologic properties. These include
      irreversible insertion of the pores in lipid membranes, formation of
      heterodisperse pore sizes, inhibition by Congo red of pore formation, blockade of
      pores by zinc, and a relative lack of ion selectivity and voltage dependence.
      Although there exists some information about the physical structure of these
      pores, molecular modeling suggests that 4-6-mer amyloid subunits may assemble
      into 24-mer pore-forming aggregates. The molecular structure of these pores may
      resemble the beta-barrel structure of the toxics pore formed by bacterial toxins,
      such as staphylococcal alpha-hemolysin, anthrax toxin, and Clostridium
      perfringolysin.

PMID- 22482455
TI  - Protein quality control in neurodegenerative disease.
AB  - The accumulation of misfolded proteins is a common feature of many
      neurodegenerative diseases. These observations suggest a potential link between
      these disorders and protein quality control, a collection of cellular pathways
      that sense damage to proteins and facilitate their turnover. Consistent with this
      idea, activation of quality control components, such as molecular chaperones, has
      been shown to be protective in multiple neurodegenerative disease models. In
      addition, key studies have suggested that quality control deteriorates with age,
      further supporting a relationship between these processes. In this chapter, we
      discuss the evidence linking neurodegeneration to quality control and present the
      emerging models. We also speculate on why proper quality control is so difficult
      for certain proteins.

PMID- 22482452
TI  - The complex molecular biology of amyotrophic lateral sclerosis (ALS).
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder
      that causes selective death of motor neurons followed by paralysis and death. A
      subset of ALS cases is caused by mutations in the gene for Cu, Zn superoxide
      dismutase (SOD1), which impart a toxic gain of function to this antioxidant
      enzyme. This neurotoxic property is widely believed to stem from an increased
      propensity to misfold and aggregate caused by decreased stability of the native
      homodimer or a tendency to lose stabilizing posttranslational modifications.
      Study of the molecular mechanisms of SOD1-related ALS has revealed a complex
      array of interconnected pathological processes, including glutamate
      excitotoxicity, dysregulation of neurotrophic factors and axon guidance proteins,
      axonal transport defects, mitochondrial dysfunction, deficient protein quality
      control, and aberrant RNA processing. Many of these pathologies are directly
      exacerbated by misfolded and aggregated SOD1 and/or cytosolic calcium overload,
      suggesting the primacy of these events in disease etiology and their potential as
      targets for therapeutic intervention.

PMID- 22482453
TI  - Tau and tauopathies.
AB  - Tauopathies are age-related neurodegenerative diseases that are characterized by
      the presence of aggregates of abnormally phosphorylated tau. As tau was
      originally discovered as a microtubule-associated protein, it has been
      hypothesized that neurodegeneration results from a loss of the ability of tau to
      associate with microtubules. However, tau has been found to have other functions
      aside from the promotion and stabilization of microtubule assembly. It is
      conceivable that such functions may be affected by the abnormal phosphorylation
      of tau and might have consequences for neuronal function or viability. This
      chapter provides an overview of tau structure, functions, and its involvement in
      neurodegenerative diseases.

PMID- 22482457
TI  - Fungal prions.
AB  - For both mammalian and fungal prion proteins, conformational templating drives
      the phenomenon of protein-only infectivity. The conformational conversion of a
      protein to its transmissible prion state is associated with changes to host
      cellular physiology. In mammals, this change is synonymous with disease, whereas
      in fungi no notable detrimental effect on the host is typically observed.
      Instead, fungal prions can serve as epigenetic regulators of inheritance in the
      form of partial loss-of-function phenotypes. In the presence of environmental
      challenges, the prion state [PRION(+)], with its resource for phenotypic
      plasticity, can be associated with a growth advantage. The growing number of
      yeast proteins that can switch to a heritable [PRION(+)] form represents diverse
      and metabolically penetrating cellular functions, suggesting that the [PRION(+)]
      state in yeast is a functional one, albeit rarely found in nature. In this
      chapter, we introduce the biochemical and genetic properties of fungal prions,
      many of which are shared by the mammalian prion protein PrP, and then outline the
      major contributions that studies on fungal prions have made to prion biology.

PMID- 22482458
TI  - Molecular biology of neurodegenerative diseases. Preface.

PMID- 22482459
TI  - Proton transfer reaction mass spectrometry and the unambiguous real-time
      detection of 2,4,6 trinitrotoluene.
AB  - Fears of terrorist attacks have led to the development of various technologies
      for the real-time detection of explosives, but all suffer from potential
      ambiguities in the assignment of threat agents. Using proton transfer reaction
      mass spectrometry (PTR-MS), an unusual bias dependence in the detection
      sensitivity of 2,4,6 trinitrotoluene (TNT) on the reduced electric field (E/N)
      has been observed. For protonated TNT, rather than decreasing signal intensity
      with increasing E/N, which is the more usual sensitivity pattern observed in PTR
      MS studies, an anomalous behavior is first observed, whereby the signal intensity
      initially rises with increasing E/N. We relate this to unexpected ion-molecule
      chemistry based upon comparisons of measurements taken with related nitroaromatic
      compounds (1,3,5 trinitrobenzene, 1,3 dinitrobenzene, and 2,4 dinitrotoluene) and
      electronic structure calculations. This dependence provides an easily measurable
      signature that can be used to provide a rapid highly selective analytical
      procedure to minimize false positives for the detection of TNT. This has major
      implications for Homeland Security and, in addition, has the potential of making
      instrumentation cost-effective for use in security areas. This study shows that
      an understanding of fundamental ion-molecule chemistry occurring in low-pressure
      drift tubes is needed to exploit selectivity and sensitivity for analytical
      purposes.

PMID- 22482460
TI  - Surface defects on plate-shaped silver nanoparticles contribute to its hazard
      potential in a fish gill cell line and zebrafish embryos.
AB  - We investigated and compared nanosize Ag spheres, plates, and wires in a fish
      gill epithelial cell line (RT-W1) and in zebrafish embryos to understand the
      mechanism of toxicity of an engineered nanomaterial raising considerable
      environmental concern. While most of the Ag nanoparticles induced N-acetyl
      cysteine sensitive oxidative stress effects in RT-W1, Ag nanoplates were
      considerably more toxic than other particle shapes. Interestingly, while Ag ion
      shedding and bioavailability failed to comprehensively explain the high toxicity
      of the nanoplates, cellular injury required direct particle contact, resulting in
      cell membrane lysis in RT-W1 as well as red blood cells (RBC). Ag nanoplates were
      also considerably more toxic in zebrafish embryos in spite of their lesser
      ability to shed Ag into the exposure medium. To elucidate the "surface
      reactivity" of Ag nanoplates, high-resolution transmission electron microscopy
      was performed and demonstrated a high level of crystal defects (stacking faults
      and point defects) on the nanoplate surfaces. Surface coating with cysteine was
      used to passivate the surface defects and demonstrated a reduction of toxicity in
      RT-W1 cells, RBC, and zebrafish embryos. This study demonstrates the important
      role of crystal defects in contributing to Ag nanoparticle toxicity in addition
      to the established roles of Ag ion shedding by Ag nanoparticles. The excellent
      correlation between the in vitro and in vivo toxicological assessment illustrates
      the utility of using a fish cell line in parallel with zebrafish embryos to
      perform a predictive environmental toxicological paradigm.

PMID- 22482461
TI  - A T-shaped amphiphilic molecule forms closed vesicles in water and bicelles in
      mixtures with a membrane lipid.
AB  - The T-shaped amphiphilic molecule A6/6 forms a columnar hexagonal liquid
      crystalline phase between the crystalline and the isotropic liquid when studied
      in bulk (Chen et al., 2005). Because of the hydrophilic and flexible
      oligo(oxyethylene) side chain terminated by a 1-acylamino-1-deoxy-d-sorbitol
      moiety attached to a rigid terphenyl core with terminal hexyloxy alkyl chains, it
      was expected that also formation of lyotropic phases could be possible. We
      therefore studied the behavior of A6/6 in water and also in mixtures with bilayer
      forming phospholipids, such as dipalmitoyl-phosphatidylcholine (DPPC), using
      differential scanning calorimetry (DSC), transmission electron microscopy (TEM),
      cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS),
      and solid-state nuclear magnetic resonance (ssNMR). DSC showed for the pure A6/6
      suspended in water a phase transition at ca. 23  degrees C. TEM and cryo-TEM
      showed vesicular as well as layered structures for pure A6/6 in water below and
      above this phase transition. By atomic force microscopy (AFM), the thickness of
      the layer was found to be 5-6 nm. This leads to a model for a bilayer formed by
      A6/6 with the laterally attached polar side chains shielding the hydrophobic
      layer built up by the terphenyl core with the terminal alkyl chains of the
      molecules. For DPPC:A6/6 mixtures (10:1), the DSC curves indicated a
      stabilization of the lamellar gel phase of DPPC. Negative staining TEM and cryo
      TEM images showed planar bilayers with hexagonal morphology and diameters between
      50 and 200 nm. The hydrodynamic radius of these aggregates in water, investigated
      by dynamic light scattering (DLS) as a function of time and temperature, did not
      change indicating a very stable aggregate structure. The findings lead to the
      proposition of a new bicellar structure formed by A6/6 with DPPC. In this model,
      the bilayer edges are covered by the T-shaped amphiphilic molecules preventing
      very effectively the aggregation to larger structures. 

PMID- 22482456
TI  - Biology of mitochondria in neurodegenerative diseases.
AB  - Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral
      sclerosis (ALS) are the most common human adult-onset neurodegenerative diseases.
      They are characterized by prominent age-related neurodegeneration in selectively
      vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes
      causing these diseases have been identified. Nevertheless, the mechanisms of the
      neuronal degeneration in these familial diseases, and in the more common
      idiopathic (sporadic) diseases, are unresolved. Genetic, biochemical, and
      morphological analyses of human AD, PD, and ALS, as well as their cell and animal
      models, reveal that mitochondria could have roles in this neurodegeneration. The
      varied functions and properties of mitochondria might render subsets of
      selectively vulnerable neurons intrinsically susceptible to cellular aging and
      stress and the overlying genetic variations. In AD, alterations in enzymes
      involved in oxidative phosphorylation, oxidative damage, and mitochondrial
      binding of Abeta and amyloid precursor protein have been reported. In PD,
      mutations in mitochondrial proteins have been identified and mitochondrial DNA
      mutations have been found in neurons in the substantia nigra. In ALS, changes
      occur in mitochondrial respiratory chain enzymes and mitochondrial programmed
      cell death proteins. Transgenic mouse models of human neurodegenerative disease
      are beginning to reveal possible principles governing the biology of selective
      neuronal vulnerability that implicate mitochondria and the mitochondrial
      permeability transition pore. This chapter reviews several aspects of
      mitochondrial biology and how mitochondrial pathobiology might contribute to the
      mechanisms of neurodegeneration in AD, PD, and ALS.

PMID- 22482462
TI  - Differences in the structural stability and cooperativity between monomeric
      variants of natural and de novo Cro proteins revealed by high-pressure Fourier
      transform infrared spectroscopy.
AB  - It is widely accepted that pressure affects the structure and dynamics of
      proteins; however, the underlying mechanism remains unresolved. Our previous
      studies have investigated the effects of pressure on fundamental secondary
      structural elements using model peptides, because these peptides represent a
      basis for understanding the effects of pressure on more complex structures. This
      study targeted monomeric variants of naturally occurring bacteriophage lambda Cro
      (natural Cro) and de novo designed lambda Cro (SN4m), which are alpha + beta
      proteins. The sequence of SN4m is 75% different from that of natural Cro, but the
      structures are almost identical. Consequently, a comparison of the folding
      properties of these proteins is of interest. Pressure- and temperature-variable
      Fourier transform infrared spectroscopic analyses revealed that the alpha-helices
      and beta-sheets of natural Cro are cooperatively and reversibly unfolded by
      pressure and temperature, whereas those of SN4m are not cooperatively unfolded by
      pressure; i.e., the alpha-helices of SN4m unfold at significantly higher
      pressures than the beta-sheets and irreversibly unfold with increases in
      temperature. The higher unfolding pressure for the alpha-helices of SN4m
      indicates the presence of an intermediate structure of SN4m that does not retain
      beta-sheet structure but does preserve the alpha-helices. These results
      demonstrate that the alpha-helices of natural Cro are stabilized by global
      tertiary contacts among the alpha-helices and the beta-sheets, whereas the alpha
      helices of SN4m are stabilized by local tertiary contacts between the alpha
      helices.

PMID- 22482465
TI  - An evaluation of expert reports with regard to adherence to current quality
      standards.
AB  - In early 2008 the penal system of Lower Saxony established a specialised
      department responsible for risk assessment regarding all prison inmates in that
      state. The department generates approximately 200 risk assessment expert reports
      per year, mainly on questions such as the inmates' aptitude for social therapy,
      relaxation of imprisonment conditions, and transfer to an open prison. Prof. Dr.
      Konrad and Dr. Heering (from the Charite's Institute for Forensic Psychiatry)
      have been accompanying the work of this department scientifically for at least 2
      years by offering a scientific exchange and by reviewing random samples of the
      risk assessments and verifying the application of current standards. It is of
      particular interest to examine which methods are used and which topics are
      discussed with the inmates during the exploration for risk assessment expert
      reports, whether or not standardised risk scales are applied, and finally which
      conclusions are drawn from the results of the exploration and the information
      which could be gathered from court and prison files.

PMID- 22482463
TI  - Immunosuppression decreases inflammation and increases AAV6-hSERCA2a-mediated
      SERCA2a expression.
AB  - The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays
      a central role in cardiac contraction, shows decreased expression in heart
      failure (HF). Increasing SERCA2a expression in HF models improves cardiac
      function. We used direct cardiac delivery of adeno-associated virus encoding
      human SERCA2a (AAV6-hSERCA2a) in HF and normal canine models to study safety,
      efficacy, and the effects of immunosuppression. Tachycardic-paced dogs received
      left ventricle (LV) wall injection of AAV6-hSERCA2a or solvent. Pacing continued
      postinjection for 2 or 6 weeks, until euthanasia. Tissue/serum samples were
      analyzed for hSERCA2a expression (Western blot) and immune responses (histology
      and AAV6-neutralizing antibodies). Nonpaced dogs received AAV6-hSERCA2a and were
      analyzed at 12 weeks; a parallel cohort received AAV-hSERCA2a and
      immunosuppression. AAV-mediated cardiac expression of hSERCA2a peaked at 2 weeks
      and then declined (to ~50%; p<0.03, 6 vs. 2 weeks). LV end diastolic and end
      systolic diameters decreased in 6-week dogs treated with AAV6-hSERCA2a (p<0.05)
      whereas LV diameters increased in control dogs. Dogs receiving AAV6-hSERCA2a
      developed neutralizing antibodies (titer >=1:120) and cardiac cellular
      infiltration. Immunosuppression dramatically reduced immune responses (reduced
      inflammation and neutralizing antibody titers <1:20), and maintained hSERCA2a
      expression. Thus cardiac injection of AAV6-hSERCA2a promotes local hSERCA2a
      expression and improves cardiac function. However, the hSERCA2a protein level is
      reduced by host immune responses. Immunosuppression alleviates immune responses
      and sustains transgene expression, and may be an important adjuvant for clinical
      gene therapy trials.

PMID- 22482466
TI  - New features, new vessels, and ongoing challenges.

PMID- 22482467
TI  - The origin of tears. The Aqueo-serous component in the XIX and XX centuries.

PMID- 22482469
TI  - Appraisal of patient-reported outcome instruments available for randomized
      clinical trials in dry eye: revisiting the standards.
AB  - Clinical signs in dry eye (DE) often underestimate the severity of the condition,
      correlating poorly with symptoms and the impact on patients' health-related
      quality of life (HRQL). Patient-reported outcome (PRO) questionnaires are
      therefore essential to accurately evaluate the health status of DE patients and
      the severity of their condition. A comprehensive evaluation of HRQL in addition
      to clinical signs and visual function is necessary to fully characterize the
      impact of DE on patients' health. Growing interest in PRO measures and their
      implementation in clinical trials has resulted in more formal guidance on the
      design and properties of these instruments. To be scientifically sound and
      accepted by regulatory authorities, an instrument's development process and its
      appropriateness for use in the target population, its psychometric properties and
      responsiveness must be described. To address the recent health authority
      guidance, this review discusses the design, development methodology, and
      performance of currently available PRO instruments for DE.

PMID- 22482471
TI  - Report of the TFOS/ARVO Symposium on global treatments for dry eye disease: an
      unmet need.
AB  - In September 2010, a Symposium in Florence, Italy, was held to address the unmet
      need for global treatments for dry eye disease (DED). It was sponsored by The
      Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and co-sponsored by
      the Association for Research in Vision & Ophthalmology (www.arvo.org). The
      Symposium objectives were two-fold: first, to discuss accepted and emerging
      clinical endpoints of DED with regulatory experts from around the world; and
      second, to consider how to improve clinical trials of treatments for DED. The
      Symposium focused on the personal and collective burden of DED, as well as the
      developmental and regulatory challenges associated with generating new DED
      therapeutics. This article provides a synopsis of many of the presentations,
      discussions and recommendations of this Symposium.

PMID- 22482470
TI  - Elevated IGFBP3 levels in diabetic tears: a negative regulator of IGF-1 signaling
      in the corneal epithelium.
AB  - To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in
      telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under
      elevated glucose conditions and to correlate these changes with total and
      phosphorylated levels of IGF-1R. Tear samples were collected noninvasively from
      diabetic subjects and non-diabetic controls; corneal sensitivity was assessed
      using a Cochet-Bonnet Aesthesiometer. Conditioned media were collected following
      culture of hTCEpi cells in normal (5 mM) and elevated (25 mM) glucose conditions;
      mannitol was used as an osmotic control. IGFBP3, IGF-1, and phosphorylated IGF-1R
      levels were assessed by ELISA. IGFBP3 and IGF-1R mRNA were assessed by real-time
      polymerase chain reaction (PCR). Total and phosphorylated IGF-1R expression in
      whole cell lysates was assessed by western blot. There was a 2.8-fold increase in
      IGFBP3 in diabetic tears compared to non-diabetic controls (P=0.006); IGF-1
      levels were not significantly altered. No difference in corneal sensitivity was
      detected between groups. The concentration of IGFBP3 in tears was independent of
      IGF-1. Consistent with human tear measurements in vivo, IGFBP3 secretion was
      increased 2.2 fold (P<0.001) following culture of hTCEpi cells under elevated
      glucose conditions in vitro. Treatment with glucose and the mannitol control
      reduced IGFBP3 mRNA (P<0.001). Total IGF-1R levels were unchanged. The increase
      in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls
      blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro.
      Taken together, these in vivo and confirmatory in vitro findings suggest that the
      observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling
      in the diabetic cornea. A long-term increase in IGFBP3 may contribute to
      epithelial compromise and the pathogenesis of ocular surface complications
      reported in diabetes.

PMID- 22482472
TI  - How do drugs get their brand names?

PMID- 22482468
TI  - Corneal neovascularization and the utility of topical VEGF inhibition:
      ranibizumab (Lucentis) vs bevacizumab (Avastin).
AB  - Corneal avascularity is necessary for the preservation of optimal vision. The
      cornea maintains a dynamic balance between pro- and antiangiogenic factors that
      allows it to remain avascular under normal homeostatic conditions; however,
      corneal avascularity can be compromised by pathologic conditions that negate the
      cornea's "angiogenic privilege." The clinical relevance of corneal
      neovascularization has long been recognized, but management of this condition has
      been hindered by a lack of safe and effective therapeutic modalities. Herein, the
      etiology, epidemiology, pathogenesis, and treatment of corneal neovascularization
      are reviewed. Additionally, the authors' recent findings regarding the clinical
      utility of topical ranibizumab (Lucentis(r)) and bevacizumab (Avastin(r)) in the
      treatment of corneal neovascularization are summarized. These findings clearly
      indicate that ranibizumab and bevacizumab are safe and effective treatments for
      corneal neovascularization when appropriate precautions are observed. Although
      direct comparisons are not conclusive, the results suggest that ranibizumab may
      be modestly superior to bevacizumab in terms of both onset of action and degree
      of efficacy. In order to justify the increased cost of ranibizumab, it will be
      necessary to demonstrate meaningful treatment superiority in a prospective,
      randomized, head-to-head comparison study.

PMID- 22482473
TI  - Personal profile. David Kellner, founding publisher of The Ocular Surface.

PMID- 22482474
TI  - Percutaneous alcohol septal ablation for hypertrophic obstructive cardiomyopathy:
      technical review and long-term clinical and echocardiographic outcomes.
AB  - BACKGROUND: Percutaneous septal ablation by alcohol-induced septal branch
      occlusion was introduced as a new treatment option in symptomatic patients with
      hypertrophic obstructive cardiomyopathy (HOCM). Our aim was to evaluate
      procedural and long-term clinical and echocardiographic outcomes in patients with
      HOCM treated by alcohol septal ablation (ASA) at our center. METHODS: This single
      center retrospective study included 14 consecutive HOCM patients undergoing
      percutaneous ASA (66.4 +/- 12.1 years, 71.4% female). At baseline all patients
      presented persistent symptoms despite optimized medical treatment, left
      ventricular outflow tract (LVOT) obstruction with a peak gradient > 50 mmHg,
      systolic anterior motion of the mitral valve, and ventricular septal thickness >
      or = 15 mm. ASA was considered successful when the LVOT pressure gradient fell to
      less than 50% of baseline value. All patients had echocardiographic evaluation at
      baseline, intraprocedure and at follow-up, and a long-term clinical follow-up (25
      +/- 38 months) with evaluation of functional class and occurrence of symptoms or
      cardiovascular events. RESULTS: Percutaneous ASA achieved a 71.4% acute and 85.7%
      long-term success rate. Peak LVOT gradient decreased from 104 +/- 40 mmHg at
      baseline to 58 +/- 30 mmHg intraprocedure (p = 0.03) and 35 +/- 26 mmHg at follow
      up (p = 0.001); total gradient decrease was 75 +/- 43 mmHg. Ventricular septal
      thickness and mitral regurgitation also presented significant decreases during
      follow-up (from 24 +/- 5 mm to 18 +/- 4 mm, p = 0.02, and from grade 2.4 +/- 0.6
      to 1.4 +/- 0.5, p < 0.001, respectively). A tendency for long-term improvement in
      NYHA functional class (from 2.6 +/- 1.1 to 1.8 +/- 1.4, p = 0.09) was observed.
      Procedural complications occurred in 6.7% of patients; two deaths and one
      transient ischemic attack occurred in-hospital, but no long-term clinical events
      were recorded. CONCLUSIONS: Percutaneous ASA is an effective treatment for
      symptomatic patients with HOCM, obtaining a marked decrease in LVOT pressure
      gradient and symptomatic improvement. Despite the occurrence of a significant
      number of procedural complications, the favorable long-term outcomes underline
      the potential of ASA as a percutaneous alternative to surgical myectomy.

PMID- 22482476
TI  - [Breastfeeding and atopic dermatitis].

PMID- 22482475
TI  - Changes in DNA methylation and transgenerational mobilization of a transposable
      element (mPing) by the topoisomerase II inhibitor, etoposide, in rice.
AB  - BACKGROUND: Etoposide (epipodophyllotoxin) is a chemical commonly used as an anti
      cancer drug which inhibits DNA synthesis by blocking topoisomerase II activity.
      Previous studies in animal cells have demonstrated that etoposide constitutes a
      genotoxic stress which may induce genomic instability including mobilization of
      normally quiescent transposable elements (TEs). However, it remained unknown
      whether similar genetically mutagenic effects could be imposed by etoposide in
      plant cells. Also, no information is available with regard to whether the drug
      may cause a perturbation of epigenetic stability in any organism. RESULTS: To
      investigate whether etoposide could generate genetic and/or epigenetic
      instability in plant cells, we applied etoposide to germinating seeds of six
      cultivated rice (Oryza sativa L.) genotypes including both subspecies, japonica
      and indica. Based on the methylation-sensitive gel-blotting results, epigenetic
      changes in DNA methylation of three TEs (Tos17, Osr23 and Osr36) and two protein
      encoding genes (Homeobox and CDPK-related genes) were detected in the etoposide
      treated plants (S0 generation) in four of the six studied japonica cultivars,
      Nipponbare, RZ1, RZ2, and RZ35, but not in the rest japonica cultivar (Matsumae)
      and the indica cultivar (93-11). DNA methylation changes in the etoposide-treated
      S0 rice plants were validated by bisulfite sequencing at both of two analyzed
      loci (Tos17 and Osr36). Transpositional activity was tested for eight TEs
      endogenous to the rice genome in both the S0 plants and their selfed progenies
      (S1 and S2) of one of the cultivars, RZ1, which manifested heritable phenotypic
      variations. Results indicated that no transposition occurred in the etoposide
      treated S0 plants for any of the TEs. Nonetheless, a MITE transposon, mPing,
      showed rampant mobilization in the S1 and S2 progenies descended from the drug
      treated S0 plants. CONCLUSIONS: Our results demonstrate that etoposide imposes a
      similar genotoxic stress on plant cells as it does on animal and human cells,
      which may induce transgenerational genomic instability by instigating
      transpositional activation of otherwise dormant TEs. In addition, we show for the
      first time that etoposide may induce epigenetic instability in the form of
      altered DNA methylation patterns in eukaryotes. However, penetrance of the
      genotoxic effects of etoposide on plant cells, as being reflected as genetic and
      epigenetic instability, appears to be in a strictly genotype- and/or generation
      dependent manner.

PMID- 22482477
TI  - [Attitude of medical students towards breastfeeding].

PMID- 22482478
TI  - [Atopic dermatitis and prolonged exclusive breast-feeding].
AB  - BACKGROUND: We sought to compare the prevalence of exclusive breastfeeding
      throughout at least the first 6 months of life in patients presenting atopic
      dermatitis (AD) with a control group, and to check for a correlation between the
      duration of exclusive breastfeeding and the severity of AD. PATIENTS AND METHODS:
      We conducted a case-control study with prospective inclusion over a period of 3
      years. The study group consisted of 114 patients aged less than 15 years, from an
      urban area, presenting AD but with no personal or family history of atopy. Each
      patient was compared with two controls from the same town, matched for age and
      gender, with no personal or family history of atopy, and free of AD. Data
      analysis was performed using the SPSS software package, version 15.0. A P-value
      of less than 0.05 was considered as statistically significant. RESULTS: The
      prevalence of exclusive breastfeeding for at least the first 6 months of life in
      the patient group was significantly lower than in the control group (P=0.0413).
      On the other hand, AD was significantly less severe in patients exclusively
      breastfed for longer than 9 months (P=0.0079). CONCLUSION: The correlations
      recorded in our study do not allow us to draw any definite conclusions about a
      protective effect of exclusive breastfeeding with regard to AD. However, other
      benefits of extended exclusive breastfeeding justify supporting breastfeeding in
      a community with an existing sociocultural predisposition for this feeding
      method.

PMID- 22482479
TI  - [Solar protection products: efficacy and risks].
AB  - Solar protection products (SPP) containing chemical filters and/or mineral
      filters are extensively used today in photoprotection; however, concerns continue
      to be voiced about their efficacy and about their possible dangers. A rapid
      review of photoprotection strategies shows that SPP owe their photoprotective
      effect to the absence of other photoprotection methods having clearly established
      efficacy in healthy subjects; in addition, they exhibit real protective efficacy
      against the majority of harmful effects of solar radiation, provided they have
      been devised in keeping with the specifications clearly set out in the
      recommendations of the French Medicines Agency (Afssaps). Such efficacy is
      dependent on their correct usage, recently reiterated by Afssaps in its
      recommendations to end-users concerning the good use of solar products:
      application of adequate quantities of such products, selection of the appropriate
      photoprotection class based on phototype and conditions of exposure, and regular
      renewal of applications in the event of prolonged exposure and after bathing or
      profuse sweating. Solar filters have long been known to cause contact allergic
      dermatitis, irritative dermatitis and photosensitisation, and a particular risk
      has appeared with the use of octocrylene. However, debate has centred primarily
      on the risk of endocrine disturbance potentially induced by chemical filters,
      certain of which exhibit established transcutaneous penetration. The risk of
      mimicry of an effect of oestradiol has been raised on the basis of a series of
      studies, almost all of which were carried out by the same team, and which mainly
      concerned 4-methylbenzylidene-camphor (4-MBC) following oral absorption in the
      rat. The risk of this type of effect with SPPs under normal conditions of use
      seems fairly remote according to the current state of knowledge; in any event,
      within the context of the "National Fertility Action Plan", Afssaps has been
      formally requested to analyse the risk associated with cosmetic substances that
      are "reprotoxic" and/or affect endocrine function, as a result of which various
      filters are currently being reassessed for such risk. The greater alleged safety
      of mineral filters, based on the absence of introduction of risk of
      photosensitisation (as a result of which they are preferred for use in young
      children), no longer seems so clear since the introduction of titanium dioxide
      (TiO2) and zinc oxide (ZnO) in the form of nanoparticles. Afssaps drew up a risk
      assessment report concerning cutaneous penetration, genotoxicity and oncogenesis
      for TiO(2) and ZnO in nanoparticle form; further studies are needed before any
      general conclusions may be drawn. The European Scientific Committee on Consumer
      Safety (SCCS) is also carrying out an evaluation of the use of TiO(2) and of ZnO
      as UV filters. Finally, current data do not suggest that SPPs exert any harmful
      effects by inhibiting the beneficial effects of the sun, in particular, vitamin D
      synthesis.

PMID- 22482480
TI  - [Localized inflammatory alopecia of the scalp: an unusual presentation of
      tularemia].
AB  - BACKGROUND: Tularaemia is a rare arthropod-borne zoonotic infection with 20 to 70
      new cases being seen each year in France. Cutaneous ulceration and regional
      lymphadenopathy are the classical dermatological signs. Diagnosis of atypical
      forms is more complex. OBSERVATION: A 48-year-old woman was admitted for an
      erythematous papular alopecic lesion of the scalp accompanied by fever, chills
      and cervical lymphadenopathy. Initial antibiotic therapy for 20 days with
      amoxicillin clavulanate was ineffective. The patient's history included an
      episode of hunting in the forest three days before the onset of signs. Finally,
      serology led to the diagnosis of tularaemia. Combined levofloxacin and
      doxycycline resulted in regression of the scalp lesion and lymph node disorder.
      DISCUSSION: The existence of alopecia and location on the scalp did not initially
      suggest a diagnosis of tularaemia to us. The clinical presentation was highly
      suggestive of impetigo with satellite lymphadenopathies. However, resistance to
      antibiotics and the absence of inflammation militated against this diagnosis, and
      other possible diagnoses such as a tick-borne lymphadenopathy (TIBOLA),
      borreliosis and tularaemia were discussed. The most common clinical presentation
      of tularaemia is ulceroglandular tularaemia, which predominates in 80% of cases.
      The inoculation chancre at the point of initial infection is most often located
      in the upper limbs. CONCLUSION: An inflammatory plaque on the scalp with alopecia
      may reveal tularaemia, a potentially fatal disease resulting from inoculation.

PMID- 22482481
TI  - [New toxicity of fotemustine: diffuse interstitial lung disease].
AB  - BACKGROUND: Fotemustine is an alkylating cytostatic drug belonging to the
      nitrosourea family and is used in particular in the treatment of disseminated
      malignant melanoma. Herein, we report a case of interstitial lung disease
      associated with fotemustine. PATIENTS AND METHODS: An 81-year-old man treated
      with fotemustine for metastatic melanoma presented acute interstitial lung
      disease 20 days after a fourth course of fotemustine monotherapy. The condition
      regressed spontaneously, with the patient returning to the clinical, radiological
      and blood gas status that had preceded fotemustine treatment. After other
      potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity
      was considered and this treatment was definitively withdrawn. DISCUSSION: Other
      cytostatic agents belonging to the nitrosourea family can cause similar pictures,
      with a number of cases of interstitial lung disease thus being ascribed to
      fotemustine and dacarbazine. To our knowledge, this is the first case of
      interstitial lung disease induced by fotemustine monotherapy. This diagnosis
      should be considered where respiratory signs appear in melanoma patients
      undergoing fotemustine treatment.

PMID- 22482482
TI  - [An atypical skin rash in a setting of antiphospholipid syndrome].
AB  - BACKGROUND: Antiphospholipid syndrome (APS) is characterised by arterial or
      venous thrombosis combined with the presence of specific antibodies known as
      antiphospholipids. It is commonly associated with cutaneous signs. Herein we
      report a case of atypical cutaneous eruption occurring during the course of APS
      and we discuss the possible mechanism. PATIENTS AND METHODS: A 45-year-old woman
      consulted twice within six months for an erythematosus papular eruption around
      the neckline. She was being followed-up for antiphospholipid syndrome treated
      with fluindione (Previscan(r)), and her International Normalized Ratio (INR) was
      consistent with the prescribed anticoagulation target. Blood tests confirmed the
      presence of anticardiolipin and antiphospholipid antibodies, but no laboratory
      evidence of lupus was seen. Histopathological examination of a skin biopsy
      demonstrated the presence within the vascular lumen of a weakly eosinophilic
      anhistic substance positive for PAS stain. The patient was given acetone
      salicylic acid (Kardegic(r)) combined with fluindione, and four years later, she
      had presented no relapses. DISCUSSION: Despite a clinically evocative appearance,
      the diagnosis of lupus tumidus was ruled out in our patient by histopathological
      features, and associated systemic lupus erythematosus was repeatedly refuted on
      the basis of clinical and laboratory data. We suggest that the specific
      histological images of intraluminal deposits within the dermal vessels seen in
      this patient, although not typical of thrombosis, are associated with APS. The
      clinical remission seen from the start of antiplatelet treatment could be due to
      the action of these drugs against the obstruction of small-calibre dermal
      vessels.

PMID- 22482483
TI  - [Bullous drug eruption with Nigella sativa oil].
AB  - BACKGROUND: Nigella sativa is classically used for its various therapeutic
      properties, particularly in the field of allergic diseases. We report a case of
      bullous eruption following application of Nigella sativa oil to the skin,
      possibly involving an associated systemic mechanism linked to ingestion of the
      oil. PATIENTS AND METHODS: A 53-year-old woman was hospitalized for febrile rash
      consisting of erythematous plaques with vesicles and bullous lesions. She had
      Nigella sativa oil applied to her skin and ingested it for two weeks. Cutaneous
      histopathology revealed sub-epidermal detachment and necrosis of the epidermal
      surface consistent with toxic epidermal necrolysis. The lesions healed slowly,
      but depigmented macules persisted three months later. Patch tests for Nigella
      sativa oil were strongly positive. DISCUSSION: Erythema multiforme due to contact
      with Nigella sativa oil was initially diagnosed on the basis of lesions on skin
      where the oil was applied, as well as on cutaneous histopathology and positive
      patch tests. However, a systemic reaction such as toxic epidermal necrolysis
      could not be ruled out since the patient had also ingested the oil. The most
      likely diagnosis was thus systemic and contact bullous drug eruption. The
      discovery of new therapeutic properties of Nigella sativa in other clinical
      domains underscores the need for particular vigilance regarding future use of
      this substance on account of the risk of severe drug eruptions.

PMID- 22482484
TI  - [Cutaneous fistula due to hydatid cyst of the liver].

PMID- 22482485
TI  - [A case of necrotic arachnidism evocative of loxoscelism in Southern France].

PMID- 22482486
TI  - [Melanoma during pregnancy].

PMID- 22482487
TI  - [Devotional dermatoses].

PMID- 22482488
TI  - [Solar urticaria].

PMID- 22482489
TI  - [Keratinization disorders: further new findings].

PMID- 22482490
TI  - [Generalized lichen nitidus in a child].

PMID- 22482491
TI  - [Systemic reactivation of contact eczema following tramadol administration in a
      patient with buprenorphine-induced eczema].

PMID- 22482492
TI  - Differential effects of negative publicity on beef consumption according to
      household characteristics in South Korea.
AB  - This paper examines how South Korean households responded to an unprecedented
      boycott campaign against US beef from spring to summer of 2008, and investigates
      differential responses in relation to households' characteristics. It was found
      that beef consumption reduced by 4.8% immediately after the so-called candle
      light demonstration. Instead, pork and chicken consumption increased by 17.2% and
      16.6%, respectively. This confirms a substitution effect due to the negative
      publicity concerning US beef. It was also found that the negative publicity
      effect was transitory and the reactions of consumers were not uniform; they
      differed depending on their socio-economic characteristics. The econometric model
      revealed that younger, less-educated, and/or lower-income households were more
      susceptible to the negative publicity, and reduced their beef consumption more
      than other households.

PMID- 22482493
TI  - The challenge and the future of health care turnaround plans: evidence from the
      Italian experience.
AB  - Over the last two decades, health policy and governance in Italy have undergone
      decentralisation at the regional level. The central government was expected to
      play a guiding role in defining minimum care standards and controlling health
      expenditures at the regional level in order to keep the entire Italian National
      Health System (INHS) on track. Although health performance trends have been
      consistent across regions, public health expenditures have been variable and
      contributed to a cumulative deficit of 38 billion Euros from 2001 to 2010. To
      address the deficit, the government called for a resolution introducing a partial
      bail-out plan and later institutionalised a process to facilitate a turnaround.
      The upturn started with the development of a formal regional turnaround plan that
      proposed strategic actions to address the structural determinants of costs. The
      effectiveness of this tool was widely questioned, and many critics suggested that
      it was focused more on methods to address short-term issues than on the long-term
      strategic reconfiguration that is required for regional health systems to
      ultimately address the structural causes of deficits.We propose an interpretative
      framework to understand the advantages and disadvantages of turnaround plans, and
      we apply the findings to the development of policy recommendations for the
      structure, methods, processes and contexts of the implementation of this tool.

PMID- 22482494
TI  - Capturing phosphates with iron enhanced sand filtration.
AB  - Most treatment practices for urban runoff capture pollutants such as phosphorus
      by either settling or filtration while dissolved phosphorus, typically as
      phosphates, is untreated. Dissolved phosphorus, however, represents an average
      45% of total phosphorus in stormwater runoff and can be more than 95%. In this
      study, a new stormwater treatment technology to capture phosphate, called the
      Minnesota Filter, is introduced. The filter comprises iron filings mixed with
      sand and is tested for phosphate removal from synthetic stormwater. Results
      indicate that sand mixed with 5% iron filings captures an average of 88%
      phosphate for at least 200 m of treated depth, which is significantly greater
      than a sand filter without iron filings. Neither incorporation of iron filings
      into a sand filter nor capture of phosphates onto iron filings in column
      experiments had a significant effect on the hydraulic conductivity of the filter
      at mixtures of 5% or less iron by weight. Field applications with up to 10.7%
      iron were operated over 1 year without detrimental effects upon hydraulic
      conductivity. A model is applied and fit to column studies to predict the field
      performance of iron-enhanced sand filters. The model predictions are verified
      through the predicted performance of the filters in removing phosphates in field
      applications. Practical applications of the technology, both existing and
      proposed, are presented so stormwater managers can begin implementation.

PMID- 22482495
TI  - Adsorption behavior of pesticide methomyl on activated carbon in a high gravity
      rotating packed bed reactor.
AB  - High gravity rotating packed bed (HGRPB) reactor possesses the property of high
      mass transfer rate, which is expected to promote the adsorption rate for the
      process. In this study, HGRPB has been applied on adsorption removal of methomyl
      from solution, adopting the adsorbent of activated carbon F400. The influence of
      operating parameters of HGRPB on mass transfer such as the rotating speed (N(R)),
      the flow rate of solution (F(L)) and initial concentration of methomyl (C(b0))
      were examined. The traditionally internal mass transfer models combined with
      Freundlich isotherm were used to predict the surface and effective diffusion
      coefficients. In addition, the results have also been compared with those
      obtained from the traditional basket stirred batch reactor (BBR). The results
      showed that the larger values of N(R) and F(L) enhanced the effective
      intraparticle diffusion and provided more accessible adsorption sites so as to
      result in lower equilibrium concentration in HGRPB system when compared to SBR
      system. The results of adsorption kinetics demonstrated that surface and
      effective diffusions were both significantly greater in HGRPB system instead of
      BBR system. Furthermore, the values of Bi(S) also manifested less internal mass
      transfer resistance in HGRPB system. The contribution ratio (R(F)) of the surface
      to pore diffusion mass transport showed that the larger contribution resulted
      from the surface diffusion in HGRPB system. Therefore, the results reasonably led
      to the conclusion that when the HGRPB system applied on the adsorption of
      methomyl on F400, the lower equilibrium concentration and faster internal mass
      transfer can be obtained so as to highly possess great potential to match the
      gradually stricter environmental standard.

PMID- 22482496
TI  - Designing catalysts for functionalization of unactivated C-H bonds based on the
      CH activation reaction.
AB  - In an effort to augment or displace petroleum as a source of liquid fuels and
      chemicals, researchers are seeking lower cost technologies that convert natural
      gas (largely methane) to products such as methanol. Current methane to methanol
      technologies based on highly optimized, indirect, high-temperature chemistry
      (>800  degrees C) are prohibitively expensive. A new generation of catalysts is
      needed to rapidly convert methane and O(2) (ideally as air) directly to methanol
      (or other liquid hydrocarbons) at lower temperatures (~250  degrees C) and with
      high selectivity. Our approach is based on the reaction between CH bonds of
      hydrocarbons (RH) and transition metal complexes, L(n)M-X, to generate activated
      L(n)M-R intermediates while avoiding the formation of free radicals or
      carbocations. We have focused on the incorporation of this reaction into
      catalytic cycles by integrating the activation of the CH bond with the
      functionalization of L(n)M-R to generate the desired product and regenerate the
      L(n)M-X complex. To avoid free-radical reactions possible with the direct use of
      O(2), our approach is based on the use of air-recyclable oxidants. In addition,
      the solvent serves several roles including protection of the product, generation
      of highly active catalysts, and in some cases, as the air-regenerable oxidant. We
      postulate that there could be three distinct classes of catalyst/oxidant/solvent
      systems. The established electrophilic class combines electron-poor catalysts in
      acidic solvents that conceptually react by net removal of electrons from the
      bonding orbitals of the CH bond. The solvent protects the CH(3)OH by conversion
      to more electron-poor [CH(3)OH(2)](+) or the ester and also increases the
      electrophilicity of the catalyst by ligand protonation. The nucleophilic class
      matches electron-rich catalysts with basic solvents and conceptually reacts by
      net donation of electrons to the antibonding orbitals of the CH bond. In this
      case, the solvent could protect the CH(3)OH by deprotonation to the more electron
      rich [CH(3)O](-) and increases the nucleophilicity of the catalysts by ligand
      deprotonation. The third grouping involves ambiphilic catalysts that can
      conceptually react with both the HOMO and LUMO of the CH bond and would typically
      involve neutral reaction solvents. We call this continuum base- or acid-modulated
      (BAM) catalysis. In this Account, we describe our efforts to design catalysts
      following these general principles. We have had the most success with designing
      electrophilic systems, but unfortunately, the essential role of the acidic
      solvent also led to catalyst inhibition by CH(3)OH above ~1 M. The ambiphilic
      catalysts reduced this product inhibition but were too slow and inefficient. To
      date, we have designed new base-assisted CH activation and L(n)M-R
      fuctionalization reactions and are working to integrate these into a complete,
      working catalytic cycle. Although we have yet to design a system that could
      supplant commercial processes, continued exploration of the BAM catalysis
      continuum may lead to new systems that will succeed in addressing this valuable
      goal.

PMID- 22482497
TI  - How to remake a fibroblast into a neural stem cell.
AB  - In this issue of Cell Stem Cell and in a recent issue of PNAS, Thier et al.
      (2012), Han et al. (2012), and Lujan et al. (2012) report the derivation of
      multipotent neural stem/progenitor cells from cultured mouse fibroblasts using
      distinct reprograming approaches.

PMID- 22482498
TI  - Generation of transplantable striatal projection neurons from human ESCs.
AB  - In this issue of Cell Stem Cell, Ma et al. (2012) report a differentiation
      protocol for generating striatal projection neurons from human embryonic stem
      cells with high efficiency. The cells survive transplantation, reconnect striatal
      circuitry, and restore motor function in a mouse model of striatal
      neurodegeneration that mimics the central pathohology of Huntington's disease.

PMID- 22482499
TI  - Targeting beta-catenin in CML: leukemia stem cells beware!
AB  - In this issue of Cell Stem Cell, Heidel et al. (2012) use genetic and
      pharmacological approaches to reveal that Wnt/beta-catenin signaling is required
      for leukemic stem cell (LSC) maintenance in chronic myeloid leukemia. They
      demonstrate that beta-catenin inactivation targets imanitib-resistant LSCs in
      vivo.

PMID- 22482500
TI  - In epigenetic therapy, less is more.
AB  - How DNA methylation inhibitors exert their anticancer effects in patients is not
      well understood. In the latest issue of Cancer Cell, Tsai et al. (2012) use low
      dose drug treatment to induce persistent attenuation of tumorigenicity by
      targeting tumor-initiating cells.

PMID- 22482501
TI  - Directing lung endoderm differentiation in pluripotent stem cells.
AB  - The lung is composed of numerous epithelial lineages that arise from the anterior
      foregut endoderm. This review discusses how insights into the signaling
      mechanisms that regulate lung endoderm specification and subsequent
      differentiation have recently been exploited to direct differentiation of
      hESCs/iPSCs into expandable lung progenitors.

PMID- 22482502
TI  - The stem cell niche in regenerative medicine.
AB  - Stem cells are fundamental units for achieving regenerative therapies, which
      leads naturally to a theoretical and experimental focus on these cells for
      therapeutic screening and intervention. A growing body of data in many tissue
      systems indicates that stem cell function is critically influenced by extrinsic
      signals derived from the microenvironment, or "niche." In this vein, the stem
      cell niche represents a significant, and largely untapped, entry point for
      therapeutic modulation of stem cell behavior. This Perspective will discuss how
      the niche influences stem cells in homeostasis, in the progression of
      degenerative and malignant diseases, and in therapeutic strategies for tissue
      repair.

PMID- 22482503
TI  - Self-renewing endodermal progenitor lines generated from human pluripotent stem
      cells.
AB  - The use of human pluripotent stem cells for laboratory studies and cell-based
      therapies is hampered by their tumor-forming potential and limited ability to
      generate pure populations of differentiated cell types in vitro. To address these
      issues, we established endodermal progenitor (EP) cell lines from human embryonic
      and induced pluripotent stem cells. Optimized growth conditions were established
      that allow near unlimited (>10(16)) EP cell self-renewal in which they display a
      morphology and gene expression pattern characteristic of definitive endoderm.
      Upon manipulation of their culture conditions in vitro or transplantation into
      mice, clonally derived EP cells differentiate into numerous endodermal lineages,
      including monohormonal glucose-responsive pancreatic beta-cells, hepatocytes, and
      intestinal epithelia. Importantly, EP cells are nontumorigenic in vivo. Thus, EP
      cells represent a powerful tool to study endoderm specification and offer a
      potentially safe source of endodermal-derived tissues for transplantation
      therapies.

PMID- 22482504
TI  - Generation of multipotent lung and airway progenitors from mouse ESCs and patient
      specific cystic fibrosis iPSCs.
AB  - Deriving lung progenitors from patient-specific pluripotent cells is a key step
      in producing differentiated lung epithelium for disease modeling and
      transplantation. By mimicking the signaling events that occur during mouse lung
      development, we generated murine lung progenitors in a series of discrete steps.
      Definitive endoderm derived from mouse embryonic stem cells (ESCs) was converted
      into foregut endoderm, then into replicating Nkx2.1+ lung endoderm, and finally
      into multipotent embryonic lung progenitor and airway progenitor cells. We
      demonstrated that precisely-timed BMP, FGF, and WNT signaling are required for
      NKX2.1 induction. Mouse ESC-derived Nkx2.1+ progenitor cells formed respiratory
      epithelium (tracheospheres) when transplanted subcutaneously into mice. We then
      adapted this strategy to produce disease-specific lung progenitor cells from
      human Cystic Fibrosis induced pluripotent stem cells (iPSCs), creating a platform
      for dissecting human lung disease. These disease-specific human lung progenitors
      formed respiratory epithelium when subcutaneously engrafted into immunodeficient
      mice.

PMID- 22482505
TI  - Efficient derivation of purified lung and thyroid progenitors from embryonic stem
      cells.
AB  - Two populations of Nkx2-1(+) progenitors in the developing foregut endoderm give
      rise to the entire postnatal lung and thyroid epithelium, but little is known
      about these cells because they are difficult to isolate in a pure form. We
      demonstrate here the purification and directed differentiation of primordial lung
      and thyroid progenitors derived from mouse embryonic stem cells (ESCs).
      Inhibition of TGFbeta and BMP signaling, followed by combinatorial stimulation of
      BMP and FGF signaling, can specify these cells efficiently from definitive
      endodermal precursors. When derived using Nkx2-1(GFP) knockin reporter ESCs,
      these progenitors can be purified for expansion in culture and have a
      transcriptome that overlaps with developing lung epithelium. Upon induction, they
      can express a broad repertoire of markers indicative of lung and thyroid lineages
      and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure
      population of progenitors able to recapitulate the developmental milestones of
      lung/thyroid development.

PMID- 22482506
TI  - Genetic and pharmacologic inhibition of beta-catenin targets imatinib-resistant
      leukemia stem cells in CML.
AB  - A key characteristic of hematopoietic stem cells (HSCs) is the ability to self
      renew. Genetic deletion of beta-catenin during fetal HSC development leads to
      impairment of self-renewal while beta-catenin is dispensable in fully developed
      adult HSCs. Whether beta-catenin is required for maintenance of fully developed
      CML leukemia stem cells (LSCs) is unknown. Here, we use a conditional mouse model
      to show that deletion of beta-catenin after CML initiation does not lead to a
      significant increase in survival. However, deletion of beta-catenin synergizes
      with imatinib (IM) to delay disease recurrence after imatinib discontinuation and
      to abrogate CML stem cells. These effects can be mimicked by pharmacologic
      inhibition of beta-catenin via modulation of prostaglandin signaling. Treatment
      with the cyclooxygenase inhibitor indomethacin reduces beta-catenin levels and
      leads to a reduction in LSCs. In conclusion, inhibiting beta-catenin by genetic
      inactivation or pharmacologic modulation is an effective combination therapy with
      imatinib and targets CML stem cells.

PMID- 22482508
TI  - Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic
      stem cells.
AB  - Nanog, Oct4, and Sox2 are the core regulators of mouse (m)ESC pluripotency.
      Although their basic importance in human (h)ESCs has been demonstrated, the
      mechanistic functions are not well defined. Here, we identify general and cell
      line-specific requirements for NANOG, OCT4, and SOX2 in hESCs. We show that OCT4
      regulates, and interacts with, the BMP4 pathway to specify four developmental
      fates. High levels of OCT4 enable self-renewal in the absence of BMP4 but specify
      mesendoderm in the presence of BMP4. Low levels of OCT4 induce embryonic ectoderm
      differentiation in the absence of BMP4 but specify extraembryonic lineages in the
      presence of BMP4. NANOG represses embryonic ectoderm differentiation but has
      little effect on other lineages, whereas SOX2 and SOX3 are redundant and repress
      mesendoderm differentiation. Thus, instead of being panrepressors of
      differentiation, each factor controls specific cell fates. Our study revises the
      view of how self-renewal is orchestrated in hESCs.

PMID- 22482507
TI  - Epiblast stem cell-based system reveals reprogramming synergy of germline
      factors.
AB  - Epigenetic reprogramming in early germ cells is critical toward the establishment
      of totipotency, but investigations of the germline events are intractable. An
      objective cell culture-based system could provide mechanistic insight on how the
      key determinants of primordial germ cells (PGCs), including Prdm14, induce
      reprogramming in germ cells to an epigenetic ground state. Here we show a Prdm14
      Klf2 synergistic effect that can accelerate and enhance reversion of mouse
      epiblast stem cells (epiSCs) to a naive pluripotent state, including X
      reactivation and DNA demethylation. Notably, Prdm14 alone has little effect on
      epiSC reversion, but it enhances the competence for reprogramming and potentially
      PGC specification. Reprogramming of epiSCs by the combinatorial effect of Prdm14
      Klf2 involves key epigenetic changes, which might have an analogous role in PGCs.
      Our study provides a paradigm toward a systematic analysis of how other key genes
      contribute to complex and dynamic events of reprogramming in the germline.

PMID- 22482509
TI  - Coordination effects on electron distributions for rhodium complexes of the redox
      active bis(3,5-di-tert-butyl-2-phenolate)amide ligand.
AB  - New rhodium complexes of bis(3,5-di-tert-butyl-2-phenol)amine ([ONO(cat)]H(3))
      were synthesized, and their electronic properties were investigated. These
      compounds were prepared by combining [ONO(q)]K and [(cod)Rh(MU-Cl)](2) in the
      presence of an auxiliary donor ligand to yield complexes of the type [ONO]RhL(n)
      (n = 3, L = py (1); n = 2, L = PMe(3) (2a), L = PMe(2)Ph (2b), PMePh(2) (2c),
      PPh(3) (2d)). Single-crystal X-ray diffraction studies on [ONO]Rh(py)(3) (1)
      revealed a six-coordinate, octahedral rhodium complex. In the case of
      [ONO]Rh(PMe(3))(2) (2a), X-ray diffraction showed a five-coordinate, distorted
      square-pyramidal coordination environment around the rhodium center. While 1 is
      static on the NMR time scale, complexes 2a-d are fluxional, displaying both rapid
      isomerization of the square-pyramidal structure and exchange of coordinated and
      free phosphine ligands. UV-vis spectroscopy shows stark electronic differences
      between 1 and 2a-d. Whereas 1 displays a strong absorbance at 380 nm with a much
      weaker band at 585 nm in the absorption spectrum, complexes 2a-d display an
      intense (epsilon > 10(4) M(-1) cm(-1)), low-energy absorption band in the region
      580-640 nm; however, in the cases of 2a and 2b, the addition of excess phosphine
      resulted in changes to the UV-vis spectrum indicating the formation of six
      coordinate adducts [ONO]Rh(PMe(3))(3) (3a) and [ONO]Rh(PMe(2)Ph)(3) (3b),
      respectively. The experimental and DFT computational data for the six-coordinate
      complexes 1, 3a, and 3b are consistent with their formulation as classical, d(6),
      pseudo-octahedral, coordination complexes. In the five-coordinate complexes 2a
      2d, pi-bonding between the rhodium center and the [ONO] ligand leads to a high
      degree of covalency and metal-ligand electron distributions that are not
      accurately described by formal oxidation state assignments.

PMID- 22482511
TI  - Lead-free nanogenerator made from single ZnSnO3 microbelt.
AB  - We demonstrated a single-microbelt nanogenerator first made using a ZnSnO(3)
      microbelt that generated an output power of ~3 nW under a compressive and
      releasing strain of 0.8-1%. The ZnSnO(3) nanobelts/microbelts were synthesized
      using a vapor transfer process at 1173 K. The X-ray diffraction pattern shows
      that the microbelts belong to ZnSnO(3) with rhombohedral structure. An individual
      ZnSnO(3) microbelt was bonded at its ends on a flexible polystyrene substrate as
      a nanogenerator, which gives an output voltage and current of 100 mV and 30 nA,
      respectively, corresponding to an energy conversion efficiency of 4.2-6.6% (based
      on 0.8-1% strain). Our results show that ZnSnO(3) microbelts are one of the
      highly promising materials for lead-free piezoelectric energy harvesting.

PMID- 22482510
TI  - Channel surface patterning of alternating biomimetic protein combinations for
      enhanced microfluidic tumor cell isolation.
AB  - Here, we report a new method for multicomponent protein patterning in a
      microchannel and also a technique for improving immunoaffinity-based circulating
      tumor cell (CTC) capture by patterning regions of alternating adhesive proteins
      using the new method. The first of two proteins, antiepithelial cell adhesion
      molecule (anti-EpCAM), provides the specificity for CTC capture. The second, E
      selectin, increases CTC capture under shear. Patterning regions with and without
      E-selectin allows captured leukocytes, which also bind E-selectin and are
      unwanted impurities in CTC isolation, to roll a short distance and detach from
      the capture surface. This reduces leukocyte capture by up to 82%. The patterning
      is combined with a leukocyte elution step in which a calcium chelating buffer
      effectively deactivates E-selectin so that leukocytes may be rinsed away 60% more
      efficiently than with a buffer containing calcium. The alternating patterning of
      this biomimetic protein combination, used in conjunction with the elution step,
      reduces capture of leukocytes while maintaining a high tumor cell capture
      efficiency that is up to 1.9 times higher than the tumor cell capture efficiency
      of a surface with only anti-EpCAM. The new patterning technique described here
      does not require mask alignment and can be used to spatially control the
      immobilization of any two proteins or protein mixtures inside a sealed
      microfluidic channel.

PMID- 22482512
TI  - Comprehensive effects of metal ions on responsive characteristics of P(NIPAM-co
      B18C6Am).
AB  - Comprehensive investigations of the effects of species and concentrations of
      metal ions on the ion-responsive behaviors of poly(N-isopropylacrylamide-co-benzo
      18-crown-6-acrylamide) (P(NIPAM-co-B18C6Am)) are systematically carried out with
      a series of P(NIPAM-co-B18C6Am) linear copolymers and cross-linked hydrogels
      containing different crown ether contents. The results show that when the B18C6Am
      receptors form stable B18C6Am/M(n+) host-guest complexes with special ions
      (M(n+)), such as K(+), Sr(2+), Ba(2+), Hg(2+), and Pb(2+), the LCST of P(NIPAM-co
      B18C6Am) increases due to the repulsion among charged B18C6Am/M(n+) complex
      groups and the enhancement of hydrophilicity, and the order of the shift degree
      of LCST of P(NIPAM-co-B18C6Am) is Pb(2+) > Ba(2+) > Sr(2+) > Hg(2+) > K(+). With
      increasing the content of pendent crown ether groups, the LCST shift degree
      increases first and then stays unchanged when the B18C6Am content is higher than
      20 mol %. Remarkably, it is found for the first time that there exists an optimal
      ion-responsive concentration for the P(NIPAM-co-B18C6Am) linear copolymer and
      cross-linked hydrogel in response to special metal ions, at which concentration
      the P(NIPAM-co-B18C6Am) exhibits the most significant ion-responsivity either in
      the form of linear copolymers or cross-linked hydrogels. With an increase of the
      content of crown ether groups, the value of corresponding optimal ion-responsive
      concentration increases. Interestingly, there exists an optimal molar ratio of
      metal ion to crown ether for the P(NIPAM-co-B18C6Am) copolymer in response to
      Pb(2+), which is around 4.5 (mol/mol). If the ion concentration is too high, the
      ion-responsive behaviors of P(NIPAM-co-B18C6Am) may even become surprisingly
      unobvious. Therefore, to achieve satisfactory ion-responsive characteristics of
      P(NIPAM-co-B18C6Am)-based materials, both the operation temperature and the ion
      concentration should be optimized for the specific ion species. The results in
      this study provide valuable guidance for designing and applying P(NIPAM-co
      B18C6Am)-based ion-responsive materials in various applications.

PMID- 22482513
TI  - Dominant role of the 5' TAR bulge in dimerization of HIV-1 genomic RNA, but no
      evidence of TAR-TAR kissing during in vivo virus assembly.
AB  - The 5' untranslated region of HIV-1 genomic RNA (gRNA) contains two stem-loop
      structures that appear to be equally important for gRNA dimerization: the 57
      nucleotide 5' TAR, at the very 5' end, and the 35-nucleotide SL1 (nucleotides 243
      277). SL1 is well-known for containing the dimerization initiation site (DIS) in
      its apical loop. The DIS is a six-nucleotide palindrome. Here, we investigated
      the mechanism of TAR-directed gRNA dimerization. We found that the trinucleotide
      bulge (UCU24) of the 5' TAR has dominant impacts on both formation of HIV-1 RNA
      dimers and maturation of the formed dimers. The DeltaUCU trinucleotide deletion
      strongly inhibited the first process and blocked the other, thus impairing gRNA
      dimerization as severely as deletion of the entire 5' TAR, and more severely than
      deletion of the DIS, inactivation of the viral protease, or most severe mutations
      in the nucleocapsid protein. The apical loop of TAR contains a 10-nucleotide
      palindrome that has been postulated to stimulate gRNA dimerization by a TAR-TAR
      kissing mechanism analogous to the one used by SL1 to stimulate dimerization.
      Using mutations that strongly destabilize formation of the TAR palindrome duplex,
      as well as compensatory mutations that restore duplex formation to a wild-type
      like level, we found no evidence of TAR-TAR kissing, even though mutations
      nullifying the kissing potential of the TAR palindrome could impair dimerization
      by a mechanism other than hindering of SL1. However, nullifying the kissing
      potential of TAR had much less severe effects than DeltaUCU. By not uncovering a
      dimerization mechanism intrinsic to TAR, our data suggest that TAR mutations
      exert their effect 3' of TAR, yet not on SL1, because TAR and SL1 mutations have
      synergistic effects on gRNA dimerization.

PMID- 22482514
TI  - Metabolic activation of prasugrel: nature of the two competitive pathways
      resulting in the opening of its thiophene ring.
AB  - The mechanism generally admitted for the bioactivation of the antithrombotic
      prodrug, prasugrel, 1c, is its two-step enzymatic conversion into a biologically
      active thiol metabolite. The first step is an esterase-catalyzed hydrolysis of
      its acetate function leading to a thiolactone metabolite 2c. The second step was
      described as a cytochrome P450 (P450)-dependent oxidative opening of the
      thiolactone ring of 2c, with intermediate formation of a reactive sulfenic acid
      metabolite that is eventually reduced to the corresponding active thiol 3c. This
      article describes a detailed study of the metabolism of 1c by human liver
      microsomes and human sera, with an analysis by HPLC-MS under conditions allowing
      a complete separation of the thiol metabolite isomers, after derivatization with
      3'-methoxy phenacyl bromide. It shows that there are two competing metabolic
      pathways for the opening of the 2c thiolactone ring. The major one, which was
      previously described, results from a P450- and NADPH-dependent redox
      bioactivation of 2c and leads to 3c, two previously reported thiol diastereomers
      bearing an exocyclic double bond. It occurs with NADPH-supplemented human liver
      microsomes but not with human sera. The second one results from a hydrolysis of
      2c and leads to an isomer of 3c, 3c endo, in which the double bond has migrated
      from an exocyclic to an endocyclic position in the piperidine ring. It occurs
      both with human liver microsomes and human sera, and does not require NADPH.
      However, it requires Ca(2+) and is inhibited by paraoxon, which suggests that it
      is catalyzed by a thioesterase such as PON-1. Chemical experiments have confirmed
      that hydrolytic opening of thiolactone 2c exclusively leads to derivatives of the
      endo thiol isomer 3c endo.

PMID- 22482515
TI  - In vivo gene transfer strategies to achieve partial correction of von Willebrand
      disease.
AB  - von Willebrand disease (VWD), the most common hereditary coagulation disorder,
      results from mutations in the 52-exon gene for von Willebrand factor (VWF), which
      encodes an 8.4-kB cDNA. Studies with VWF cDNA plasmids have demonstrated that in
      vivo gene transfer to the liver will correct the coagulation dysfunction in VWF(
      /-) mice, but the correction is transient. To develop gene therapy for VWF that
      would mediate long-term expression of the VWF cDNA in liver, we first evaluated
      segmental pre-mRNA trans-splicing (SPTS) with two adeno-associated virus (AAV)
      serotype 8 vectors, each delivering one-half of the VWF cDNA. However, although
      the two vectors functioned well to generate VWF multimers after infection of
      cells in vitro, the efficiency of SPTS was insufficient to correct the VWF(-/-)
      mouse in vivo. As an alternative, we assessed the ability of a lentiviral vector
      to transfer the intact murine VWF cDNA in vivo directly to the neonatal liver of
      VWF(-/-) mice, using generation of VWF multimers, bleeding time, and bleeding
      volume as efficacy parameters. The VWF lentivirus generated VWF multimers and
      partially or completely corrected the coagulation defect on a persistent basis in
      33% of the treated VWF-deficient mice. On the basis of the concept that partial
      persistent correction with gene transfer could be beneficial in VWD patients,
      these observations suggest that lentiviral delivery of VWF cDNA should be
      explored as a candidate for gene therapy in patients with a severe form of VWD.

PMID- 22482519
TI  - Finding hydrogen-storage capability in iridium induced by the nanosize effect.
AB  - We report nanosize-induced hydrogen storage in Ir, which does not absorb hydrogen
      in its bulk form. The mean diameter of the obtained Ir nanoparticles was
      estimated as 1.5 +/- 0.5 nm by transmission electron microscopy. Hydrogen storage
      was confirmed by solid-state (2)H NMR and hydrogen pressure-composition isotherm
      measurements.

PMID- 22482518
TI  - Soluble helminth products suppress clinical signs in murine experimental
      autoimmune encephalomyelitis and differentially modulate human dendritic cell
      activation.
AB  - The increased incidence of auto-inflammatory and autoimmune diseases in the
      developed countries seems to be caused by an imbalance of the immune system due
      to the lack of proper regulation. Helminth parasites are well known modulators of
      the immune system and as such are of great interest for the treatment of these
      disorders. Clinical studies showed that administration of eggs of the pig
      nematode Trichuris suis to patients with inflammatory bowel disease reduces the
      disease severity. Here we demonstrate that treatment with soluble products from
      the nematodes T. suis and Trichinella spiralis induces significant suppression of
      symptoms in murine experimental autoimmune encephalomyelitis, a validated animal
      model for multiple sclerosis. These data show that infection with live nematodes
      is not a prerequisite for suppression of inflammation. To translate these results
      to the human system, the effects of soluble products of T. suis, T. spiralis and
      Schistosoma mansoni on the phenotype and function of human dendritic cells (DCs)
      were compared. Our data show that soluble products of T. suis, S. mansoni and T.
      spiralis suppress TNF-alpha and IL-12 secretion by TLR-activated human DCs, and
      that T. suis and S. mansoni, but not T. spiralis, strongly enhance expression of
      OX40L. Furthermore, helminth-primed human DCs differentially suppress the
      development of Th1 and/or Th17 cells. In conclusion, our data demonstrate that
      soluble helminth products have strong immunomodulatory capacities, but might
      exert their effects through different mechanisms. The suppressed secretion of pro
      inflammatory cytokines together with an upregulation of OX40L expression on human
      DCs might contribute to achieve this modulation.

PMID- 22482520
TI  - Liver failure and liver transplantation. Preface.

PMID- 22482522
TI  - Artificial liver support devices as treatment option for liver failure.
AB  - Non-biological artificial liver support (ALS) devices aim to remove albumin-bound
      and water-soluble toxins arising as a result of liver failure. They do not
      directly improve the liver synthetic capacity. The currently most used devices
      combine haemodialysis with albumin dialysis (MARS) or plasma separation and
      filtration (Prometheus). These devices have been used as a treatment for
      different types of liver failure: acute liver failure, acute-on-chronic liver
      failure and primary non- or poor-function after liver transplantation. Overall
      these devices are found to be safe. The following beneficial effects have been
      documented: improvement of jaundice, amelioration of haemodynamic instability,
      reduction of portal hypertension, lowering of intracranial pressure and
      improvement of hepatic encephalopathy. However, recently multicentre controlled
      trials failed to show a beneficial effect on transplant-free survival. Therefore
      the use of these devices at present seems only justified as a bridge to liver
      transplantation.

PMID- 22482521
TI  - Recent developments in acute liver failure.
AB  - Acute liver failure is a remarkably rare syndrome, the result of rapid hepatocyte
      injury occurring over days or a few weeks, and encompassing multiple etiologies,
      but all with a remarkably similar clinical picture. The clinical features of
      coagulopathy and encephalopathy characterize this severe and often fatal
      condition. To date, transplantation has been the only reliable form of rescue for
      many patients. Recent developments have included a clearer understanding of the
      different contributing etiologies, how to build a diagnosis and prognosis based
      on initial laboratory findings, a more aggressive approach to intensive care
      management and more detailed understanding of the role of transplantation in this
      setting. This review will provide an overview of standard practices and new
      research initiatives and findings for this interesting but vexing orphan disease.
      Particular attention will be paid to practical matters for clinicians to consider
      in approaching the ALF patient. Few controlled clinical trials have been possible
      because of the condition's rarity. Critical care of these rare patients is key to
      their survival and decisions must be made decisively, sometimes with inadequate
      information. Experience is helpful but experienced clinician managers are even
      rarer than the disease: few hepatologists or intensivists have in-depth
      experience with ALF patients.

PMID- 22482523
TI  - Liver transplantation for acute liver failure.
AB  - Liver transplantation is now an integral part of the management of acute liver
      failure. The challenge for clinicians is to select the appropriate candidates
      with a combination of need and high likelihood of benefiting from the transplant.
      This is achieved through a combination of prognostic modelling and ongoing
      clinical evaluation. Although the outcomes after liver transplantation are good
      the survival rates do not quite match those achieved after elective
      transplantation.

PMID- 22482524
TI  - Stem cells in liver failure.
AB  - Orthotopic liver transplantation (OLT) represents the only reliable therapeutic
      approach for acute liver failure (ALF), liver failure associated to end-stage
      chronic liver diseases (CLD) and non-metastatic liver cancer. The clinical impact
      of liver failure is relevant because of the still high ALF mortality and the
      increasing worldwide prevalence of cirrhosis that, in turn, is the main
      predisposing cause for hepatocellular carcinoma (HCC). Moreover, in the next
      decade because an increased number of patients reaching end-stage disease and
      requiring OLT may face a shortage of donor livers. This clinical scenario led
      several laboratories to explore the feasibility and efficiency of alternative
      approaches, involving cellular therapy, to counteract liver failure. The present
      chapter overviews results and concepts emerged from recent experimental and
      clinical studies in which adult or embryonic hepatocytes, hepatic stem/progenitor
      cells, induced pluripotent stem (iPS) cells as well as extrahepatic stem cells
      have been used as putative transplantable cell sources.

PMID- 22482525
TI  - Morbidity and mortality related to non-hepatic surgery in patients with liver
      cirrhosis: a systematic review.
AB  - BACKGROUND: The aim of this study is to review systematically morbidity and
      mortality after non-hepatic surgery in patients with liver cirrhosis. METHODS:
      Comprehensive searches were conducted in PubMed, Embase and the Cochrane Library
      for articles using the words: liver failure, hepatic insufficiency, liver
      cirrhosis, cirrhosis, cirrhotic, surgical procedures, operative complications,
      operative mortality, postoperative complications, surgical complication, surgical
      risk, hernia. RESULTS: Forty-six articles were selected from 5247 included after
      the initial search. Level of evidence provided in the articles varied greatly.
      Non-hepatic surgery of patients with cirrhosis resulted in increased
      postoperative morbidity and mortality compared to similar surgery for non
      cirrhotic patients. Cholecystectomy and umbilical and inguinal hernia correction
      were associated with the lowest increased morbidity and mortality while
      pancreatic surgery, cardiovascular, and trauma surgery correlated with the
      highest. The preoperative model for end stage liver disease (MELD) and Child
      Turcotte-Pugh (CTP) scores appeared to be predictive of postoperative risks.
      Portal hypertension and surgery in the emergency setting were associated with
      extra increased mortality and morbidity rates. CONCLUSION: This systematic review
      of the literature showed that in patients with liver cirrhosis who undergo non
      hepatic surgery, postoperative morbidity and mortality rates varied greatly
      depending on severity of the cirrhosis and the surgical procedure. However, the
      majority of procedures can be safely performed in patients with low MELD scores
      or CTP A cirrhosis without portal hypertension.

PMID- 22482526
TI  - Risk factors for infection after liver transplantation.
AB  - Infection is a common cause of morbidity and mortality after liver
      transplantation. Risk factors relate to transplantation factors, donor and
      recipient factors. Transplant factors include ischaemia-reperfusion damage,
      amount of intra-operative blood transfusion, level and type of immunosuppression,
      rejection, and complications, prolonged intensive care stay with dialysis or
      ventilation, type of biliary drainage, repeat operations, re-transplantation,
      antibiotics, antiviral regimen, and environment. Donor risk factors include
      infection, prolonged intensive care stay, quality of the donor liver (e.g.
      steatosis), and viral status. For the recipient the most important are MELD score
      >30, malnutrition, renal failure, acute liver failure, presence of infection or
      colonisation, and immune status for viruses like cytomegalovirus. In recent years
      it has become clear that genetic polymorphisms in innate immunity, especially the
      lectin pathway of complement activation and in Toll-like receptors importantly
      contribute to the infection risk after liver transplantation. Therefore, the risk
      for infections after liver transplantation is a multifactorial problem and all
      factors need attention to reduce this risk.

PMID- 22482527
TI  - Tolerance in liver transplantation.
AB  - Operational tolerance (OT) in liver transplant patients occurs much more
      frequently than OT of other transplanted organs; however the rate of OT varies
      considerably with the centre and patient population. Rates of OT range from 15%
      of the total liver transplant (LTX) patient population down to less than 5%. This
      review examines the reports of liver OT and compares the factors that could
      contribute to this variation. Multiple factors were examined, including the time
      from transplantation when weaning of immunosuppression (IS) was commenced, the
      rapidity of weaning, the contribution of maintenance and induction IS and the
      patient population transplanted. The approaches that might be used to increase
      the likelihood of OT are discussed and the approaches to monitoring OT in LTX
      patients are reviewed.

PMID- 22482528
TI  - Optimization of the use of Calcineurin inhibitors in liver transplantation.
AB  - Calcineurin inhibitors (CNIs), such as cyclosporin A and tacrolimus, are the
      cornerstone of maintenance immunosuppressive regimens in liver transplantation.
      CNIs prevent rejection by inhibition of calcineurin, via which lymphocyte
      proliferation and interleukin (IL)-2 production is prevented. Tacrolimus is now
      the first-choice immunosuppressant after liver transplantation, since it is
      associated with fewer episodes of rejection than cyclosporin A. In this review we
      will discuss interindividual differences, which influence tacrolimus metabolism.
      Because of these factors and the narrow therapeutic index of tacrolimus,
      monitoring of drug trough levels is necessary. Furthermore, we will discuss
      studies concerning conversion from the tacrolimus twice daily to tacrolimus once
      daily formulation in stable LT patients. Due to adverse effects of CNIs, such as
      chronic renal failure, hypertension, de novo malignancy and new-onset diabetes
      mellitus, CNI minimization strategies have been developed, which will be
      discussed too.

PMID- 22482529
TI  - Mechanistic and spectroscopic studies of metallo-beta-lactamase NDM-1.
AB  - In an effort to biochemically characterize metallo-beta-lactamase NDM-1, we
      cloned, overexpressed, purified, and characterized several maltose binding
      protein (MBP)-NDM-1 fusion proteins with different N-termini (full-length,
      Delta6, Delta21, and Delta36). All MBP-NDM-1 fusion proteins were soluble;
      however, only one, MBP-NDM-1Delta36, exhibited high activity and bound 2 equiv of
      Zn(II). Thrombin cleavage of this fusion protein resulted in the truncated NDM
      1Delta36 variant, which exhibited a k(cat) of 16 s(-1) and a K(m) of 1.1 MUM when
      using nitrocefin as a substrate, bound 2 equiv of Zn(II), and was monomeric in
      solution. Extended X-ray absorption fine structure studies of the NDM-1Delta36
      variant indicate the average metal binding site for Zn(II) in this variant
      consists of four N/O donors (two of which are histidines) and 0.5 sulfur donor
      per zinc, with a Zn-Zn distance of 3.38 A. This metal binding site is very
      similar to those of other metallo-beta-lactamases that belong to the B1 subclass.
      Pre-steady-state kinetic studies using nitrocefin and chromacef and the NDM
      1Delta36 variant indicate that the enzyme utilizes a kinetic mechanism similar to
      that used by metallo-beta-lactamases L1 and CcrA, in which a reactive nitrogen
      anion is stabilized and its protonation is rate-limiting. While they are very
      different in terms of amino acid sequence, these studies demonstrate that NDM-1
      is structurally and mechanistically very similar to metallo-beta-lactamase CcrA.

PMID- 22482530
TI  - Movement or goal: goal salience and verbal cues affect preschoolers' imitation of
      action components.
AB  - The impact of goal salience and verbal cues given by the model on 3- to 5-year
      olds' reproduction of action components (movement or goal) was investigated in an
      imitation choice task. Preschoolers watched an experimenter moving a puppet up or
      down a ramp, terminating at one of two target objects. The target objects were
      either differently colored plastic bowls (low-salient group) or sociofunctionally
      relevant objects (high-salient group). While demonstrating the action in several
      trials, the model verbalized either the movement, the goal, both the movement and
      the goal, or none of the components. Children imitated the action on a second
      ramp with reversed positions of the target objects, so they needed to decide
      whether to reproduce the observed movement or the observed end state. In the high
      salient group, preschoolers preferentially imitated the goal component, whereas
      in the low-salient group, they did not show a preference for one of the
      components. Across trials, preschoolers preferentially imitated the goal when
      this component or both components were verbalized, whereas they showed no
      preference when the movement or none of the components was emphasized. Yet,
      verbal cues seemed to have stronger effects in the low-salient condition. We
      conclude that sociofunctional salience of action goals and communicative cues of
      the model affect young children's representation of observed actions, leading to
      a selective reproduction of those action components that are relevant to the
      child.

PMID- 22482531
TI  - Near-infrared fluorescence probes for enzymes based on binding affinity
      modulation of squarylium dye scaffold.
AB  - We present a novel design strategy for near-infrared (NIR) fluorescence probes
      utilizing dye-protein interaction as a trigger for fluorescence enhancement. The
      design principle involves modification of a polymethine dye with cleavable
      functional groups that reduce the dye's protein-binding affinity. When these
      functional groups are removed by specific interaction with the target enzymes,
      the dye's protein affinity is restored, protein binding occurs, and the dye's
      fluorescence is strongly enhanced. To validate this strategy, we first designed
      and synthesized an alkaline phosphatase (ALP) sensor by introducing phosphate
      into the squarylium dye scaffold; this sensor was able to detect ALP-labeled
      secondary antibodies in Western blotting analysis. Second, we synthesized a probe
      for beta-galactosidase (widely used as a reporter of gene expression) by means of
      beta-galactosyl substitution of the squarylium scaffold; this sensor was able to
      visualize beta-galactosidase activity both in vitro and in vivo. Our strategy
      should be applicable to obtain NIR fluorescence probes for a wide range of target
      enzymes.

PMID- 22482532
TI  - Communication: Multi-state analysis of the OCS ultraviolet absorption including
      vibrational structure.
AB  - The first absorption band of OCS (carbonyl sulfide) is analyzed using potential
      energy surfaces and transition dipole moment functions of the lowest four singlet
      and the lowest four triplet states. Excitation of the 2 (1)A' state is
      predominant except at very low photon energies. It is shown that the vibrational
      structures in the center of the band are due to excitation of the 2 (3)A''
      triplet state, whereas the structures at very low energies are caused by bending
      excitation in the potential wells of states 2 (1)A' and 1 (1)A''.

PMID- 22482533
TI  - Communication: Bulkiness versus anisotropy: the optimal shape of polarizable
      Brownian nanoparticles for alignment in electric fields.
AB  - Self-assembly and alignment of anisotropic colloidal particles are important
      processes that can be influenced by external electric fields. However, dielectric
      nanoparticles are generally hard to align this way because of their small size
      and low polarizability. In this work, we employ the coupled dipole method to show
      that the minimum size parameter for which a particle may be aligned using an
      external electric field depends on the dimension ratio that defines the exact
      shape of the particle. We show, for rods, platelets, bowls, and dumbbells, that
      the optimal dimension ratio (the dimension ratio for which the size parameter
      that first allows alignment is minimal) depends on a nontrivial competition
      between particle bulkiness and anisotropy because more bulkiness implies more
      polarizable substance and thus higher polarizability, while more anisotropy
      implies a larger (relative) difference in polarizability.

PMID- 22482534
TI  - Large-scale first-principles molecular dynamics for electrochemical systems with
      O(N) methods.
AB  - A method for large-scale first-principles molecular dynamics (MD) simulations on
      electrochemical systems has been developed by combining the effective screening
      medium (ESM) method with O(N) density functional theory (DFT). This
      implementation has been significantly simplified by the introduction of neutral
      atom potentials, which minimizes the modifications to existing DFT code. In order
      to demonstrate ability of this implementation, it has been applied to an
      electrochemical system consisting of a H-Si(111) electrode, which is a candidate
      anode for high-capacity Li-ion secondary batteries, and a propylene carbonate
      (PC) solvent to simulate how PC molecules in the vicinity of the electrode
      surface respond to an imposed electric field. The large-scale MD simulation
      clearly demonstrates that the combination of the ESM and O(N) DFT methods
      provides a useful tool for first-principles investigation of complicated
      electrochemical systems such as high-capacity batteries.

PMID- 22482535
TI  - Resolution of identity approach for the Kohn-Sham correlation energy within the
      exact-exchange random-phase approximation.
AB  - Two related methods to calculate the Kohn-Sham correlation energy within the
      framework of the adiabatic-connection fluctuation-dissipation theorem are
      presented. The required coupling-strength-dependent density-density response
      functions are calculated within exact-exchange time-dependent density-functional
      theory, i.e., within time-dependent density-functional response theory using the
      full frequency-dependent exchange kernel in addition to the Coulomb kernel. The
      resulting resolution-of-identity exact-exchange random-phase approximation (RI
      EXXRPA) methods in contrast to previous EXXRPA methods employ an auxiliary basis
      set (RI basis set) to improve the computational efficiency, in particular, to
      reduce the formal scaling of the computational effort with respect to the system
      size N from N(6) to N(5). Moreover, the presented RI-EXXRPA methods, in contrast
      to previous ones, do not treat products of occupied times unoccupied orbitals as
      if they were linearly independent. Finally, terms neglected in previous EXXRPA
      methods can be included, which leads to a method designated RI-EXXRPA+, while the
      method without these extra terms is simply referred to as RI-EXXRPA. Both EXXRPA
      methods are shown to yield total energies, reaction energies of small molecules,
      and binding energies of noncovalently bonded dimers of a quality that is similar
      and in some cases even better than that obtained with quantum chemistry methods
      such as Moller-Plesset perturbation theory of second order (MP2) or with the
      coupled cluster singles doubles method. In contrast to MP2 and to conventional
      density-functional methods, the presented RI-EXXRPA methods are able to treat
      static correlation.

PMID- 22482536
TI  - A resonance mechanism of efficient energy transfer mediated by Fenna-Matthews
      Olson complex.
AB  - The Wigner-Weisskopf-type model developed by Alicki and Giraldi [J. Phys. B 44,
      154020 (2011)] is applied to the biological process of energy transfer from a
      large peripheral light harvesting antenna to the reaction center. This process is
      mediated by the Fenna-Matthews-Olson (FMO) photosynthetic complex with a
      remarkably high efficiency. The proposed model provides a simple resonance
      mechanism of this phenomenon employing exciton coherent motion and is described
      by analytical formulas. A coupling to the vibrational environment is a necessary
      component of this mechanism as well as a fine-tuning of the FMO complex
      Hamiltonian. The role of the relatively strong coupling to the energy sink in
      achieving the resonance condition and the absence of heating of the vibrational
      environment are emphasized.

PMID- 22482537
TI  - A comparison of the value of viscosity for several water models using Poiseuille
      flow in a nano-channel.
AB  - The viscosity-temperature relation is determined for the water models SPC/E,
      TIP4P, TIP4P/Ew, and TIP4P/2005 by considering Poiseuille flow inside a nano
      channel using molecular dynamics. The viscosity is determined by fitting the
      resulting velocity profile (away from the walls) to the continuum solution for a
      Newtonian fluid and then compared to experimental values. The results show that
      the TIP4P/2005 model gives the best prediction of the viscosity for the complete
      range of temperatures for liquid water, and thus it is the preferred water model
      of these considered here for simulations where the magnitude of viscosity is
      crucial. On the other hand, with the TIP4P model, the viscosity is severely
      underpredicted, and overall the model performed worst, whereas the SPC/E and
      TIP4P/Ew models perform moderately.

PMID- 22482538
TI  - Multi-layer coarse-graining polarization model for treating electrostatic
      interactions of solvated alpha-conotoxin peptides.
AB  - A multi-layer coarse-graining (CG) model is presented for treating the
      electrostatic interactions of solvated alpha-conotoxin peptides. According to the
      sensitivity to the electrostatic environment, a hybrid set of electrostatic
      parameters, such as secondary-structure- and residue-based dipoles, and atom
      centered partial charges, are adopted. For the polarization "inert" secondary
      structures and residues, the fragment dipole moments are distributed within
      narrow ranges with the magnitude close to zero. The coarse-graining fragment
      dipoles are parameterized from a large training set (10,000 configurations) to
      reproduce the electrostatic features of molecular fragments. In contrast, the
      electrostatically "sensitive" atoms exhibit large fluctuations of charges with
      the varied environments. The environment-dependent variable charges are updated
      in each energetic calculation. The electrostatic interaction of the whole
      chemical system is hence partitioned into several sub-terms coming from the
      fragment dipole-dipole, (fragment) dipole-(atom) charge, and atom charge-charge
      interactions. A large number of test calculations on the relative energies of
      cyclo-peptide conformers have demonstrated that the multi-layer CG electrostatic
      model presents better performance than the non-polarized force fields, in
      comparison with the density-functional theory and the fully polarized force field
      model. The selection of CG fragment centers, mass or geometric center, has little
      influence on the fragment-based dipole-dipole interactions. The multi-layer
      partition of electrostatic polarization is expected to be applied to many
      biologically interesting and complicated phenomena.

PMID- 22482539
TI  - Soft repulsive mixtures under gravity: brazil-nut effect, depletion bubbles,
      boundary layering, nonequilibrium shaking.
AB  - A binary mixture of particles interacting via long-ranged repulsive forces is
      studied in gravity by computer simulation and theory. The more repulsive A
      particles create a depletion zone of less repulsive B-particles around them
      reminiscent to a bubble. Applying Archimedes' principle effectively to this
      bubble, an A-particle can be lifted in a fluid background of B-particles. This
      "depletion bubble" mechanism explains and predicts a brazil-nut effect where the
      heavier A-particles float on top of the lighter B-particles. It also implies an
      effective attraction of an A-particle towards a hard container bottom wall which
      leads to boundary layering of A-particles. Additionally, we have studied a
      periodic inversion of gravity causing perpetuous mutual penetration of the
      mixture in a slit geometry. In this nonequilibrium case of time-dependent
      gravity, the boundary layering persists. Our results are based on computer
      simulations and density functional theory of a two-dimensional binary mixture of
      colloidal repulsive dipoles. The predicted effects also occur for other long
      ranged repulsive interactions and in three spatial dimensions. They are therefore
      verifiable in settling experiments on dipolar or charged colloidal mixtures as
      well as in charged granulates and dusty plasmas.

PMID- 22482540
TI  - Variational calculation of quantum mechanical/molecular mechanical free energy
      with electronic polarization of solvent.
AB  - Quantum mechanical/molecular mechanical (QM/MM) free energy calculation presents
      a significant challenge due to an excessive number of QM calculations. A useful
      approach for reducing the computational cost is that based on the mean field
      approximation to the QM subsystem. Here, we describe such a mean-field QM/MM
      theory for electronically polarizable systems by starting from the Hartree
      product ansatz for the total system and invoking a variational principle of free
      energy. The MM part is then recast to a classical polarizable model by
      introducing the charge response kernel. Numerical test shows that the potential
      of mean force (PMF) thus obtained agrees quantitatively with that obtained from a
      direct QM/MM calculation, indicating the utility of self-consistent mean-field
      approximation. Next, we apply the obtained method to prototypical reactions in
      several qualitatively different solvents and make a systematic comparison of
      polarization effects. The results show that in aqueous solution the PMF does not
      depend very much on the water models employed, while in nonaqueous solutions the
      PMF is significantly affected by explicit polarization. For example, the free
      energy barrier for a phosphoryl dissociation reaction in acetone and cyclohexane
      is found to increase by more than 10 kcal/mol when switching the solvent model
      from an empirical to explicitly polarizable one. The reason for this is discussed
      based on the parametrization of empirical nonpolarizable models.

PMID- 22482541
TI  - Field induced gradient simulations: a high throughput method for computing
      chemical potentials in multicomponent systems.
AB  - We present a simulation method for direct computation of chemical potentials in
      multicomponent systems. The method involves application of a field to generate
      spatial gradients in the species number densities at equilibrium, from which the
      chemical potential of each species is theoretically estimated. A single
      simulation yields results over a range of thermodynamic states, as in high
      throughput experiments, and the method remains computationally efficient even at
      high number densities since it does not involve particle insertion at high
      densities. We illustrate the method by Monte Carlo simulations of binary hard
      sphere mixtures of particles with different sizes in a gravitational field. The
      results of the gradient Monte Carlo method are found to be in good agreement with
      chemical potentials computed using the classical Widom particle insertion method
      for spatially uniform systems.

PMID- 22482543
TI  - Longitudinal static optical properties of hydrogen chains: finite field
      extrapolations of matrix product state calculations.
AB  - We have implemented the sweep algorithm for the variational optimization of SU(2)
      U(1) (spin and particle number) invariant matrix product states (MPS) for general
      spin and particle number invariant fermionic Hamiltonians. This class includes
      non-relativistic quantum chemical systems within the Born-Oppenheimer
      approximation. High-accuracy ab initio finite field results of the longitudinal
      static polarizabilities and second hyperpolarizabilities of one-dimensional
      hydrogen chains are presented. This allows to assess the performance of other
      quantum chemical methods. For small basis sets, MPS calculations in the
      saturation regime of the optical response properties can be performed. These
      results are extrapolated to the thermodynamic limit.

PMID- 22482544
TI  - Multireference Fock space coupled cluster method in the effective and
      intermediate Hamiltonian formulation for the (2,0) sector.
AB  - The effective and intermediate Hamiltonian (IH) multireference coupled cluster
      (CC) method with singles (S) and doubles (D) within the double electron attached
      (2,0) sector of the Fock space (FS) is formulated and implemented. The
      intermediate Hamiltonian realization of the (2,0) FS problem allows to replace
      the iterative scheme of the FS-CC equations based on the effective Hamiltonian
      with the diagonalization of the properly constructed matrix. The proposed method,
      IH-FS-CCSD (2,0), is rigorously size-extensive, easy to code, and numerically
      very efficient with the results comparable or slightly better than equation-of
      motion ones at the CCSDT (T--triples) level. The performance of the method is
      discussed on the basis of test calculations for potential energy curves of the
      systems for which double positive ions dissociate into closed shell fragments
      (e.g., Na(2) dimer). The double electron attachment (DEA) scheme can be also
      useful in determination of the excitation spectra for difficult cases. The
      example is a carbon atom which has two electrons out of the closed shell
      structure. The newly implemented method is also analyzed by plotting potential
      energy curve for twisted ethylene case as a function of a dihedral angle between
      two methylene groups. Using DEA scheme one obtains a smooth, cusp free curve.

PMID- 22482542
TI  - Quantum dynamics in continuum for proton transport--generalized correlation.
AB  - As a key process of many biological reactions such as biological energy
      transduction or human sensory systems, proton transport has attracted much
      research attention in biological, biophysical, and mathematical fields. A quantum
      dynamics in continuum framework has been proposed to study proton permeation
      through membrane proteins in our earlier work and the present work focuses on the
      generalized correlation of protons with their environment. Being complementary to
      electrostatic potentials, generalized correlations consist of proton-proton,
      proton-ion, proton-protein, and proton-water interactions. In our approach,
      protons are treated as quantum particles while other components of generalized
      correlations are described classically and in different levels of approximations
      upon simulation feasibility and difficulty. Specifically, the membrane protein is
      modeled as a group of discrete atoms, while ion densities are approximated by
      Boltzmann distributions, and water molecules are represented as a dielectric
      continuum. These proton-environment interactions are formulated as convolutions
      between number densities of species and their corresponding interaction kernels,
      in which parameters are obtained from experimental data. In the present
      formulation, generalized correlations are important components in the total
      Hamiltonian of protons, and thus is seamlessly embedded in the
      multiscale/multiphysics total variational model of the system. It takes care of
      non-electrostatic interactions, including the finite size effect, the geometry
      confinement induced channel barriers, dehydration and hydrogen bond effects, etc.
      The variational principle or the Euler-Lagrange equation is utilized to minimize
      the total energy functional, which includes the total Hamiltonian of protons, and
      obtain a new version of generalized Laplace-Beltrami equation, generalized
      Poisson-Boltzmann equation and generalized Kohn-Sham equation. A set of numerical
      algorithms, such as the matched interface and boundary method, the Dirichlet to
      Neumann mapping, Gummel iteration, and Krylov space techniques, is employed to
      improve the accuracy, efficiency, and robustness of model simulations. Finally,
      comparisons between the present model predictions and experimental data of
      current-voltage curves, as well as current-concentration curves of the Gramicidin
      A channel, verify our new model.

PMID- 22482545
TI  - First-principles calculation of thermodynamic stability of acids and bases under
      pH environment: a microscopic pH theory.
AB  - Despite being one of the most important thermodynamic variables, pH has yet to be
      incorporated into first-principles thermodynamics to calculate stability of
      acidic and basic solutes in aqueous solutions. By treating the solutes as defects
      in homogeneous liquids, we formulate a first-principles approach to calculate
      their formation energies under proton chemical potential, or pH, based on
      explicit molecular dynamics. The method draws analogy to first-principle
      calculations of defect formation energies under electron chemical potential, or
      Fermi energy, in semiconductors. From this, we propose a simple pictorial
      representation of the general theory of acid-base chemistry. By performing first
      principles molecular dynamics of liquid water models with solutes, we apply the
      formulation to calculate formation energies of various neutral and charged
      solutes such as H(+), OH(-), NH(3), NH(4)(+), HCOOH, and HCOO(-) in water. The
      deduced auto-dissociation constant of water and the difference in the pKa values
      of NH(3) and HCOOH show good agreement with known experimental values. Our first
      principles approach can be further extended and applied to other bio- and electro
      chemical molecules such as amino acids and redox reaction couples that could
      exist in aqueous environments to understand their thermodynamic stability.

PMID- 22482546
TI  - The J = 1 para levels of the v = 0 to 6 np singlet Rydberg series of molecular
      hydrogen revisited.
AB  - The energies and the widths of the J = 1 para levels of the v = 0 to 6 Rydberg np
      singlet series of molecular hydrogen with absolute intensities of the R(0) and
      P(2) absorption lines were measured by a high - resolution synchrotron radiation
      experiment and calculated through a full ab initio multichannel quantum defect
      theory approach. On the basis of the agreement between theory and experiment, 31
      levels were either reassigned or assigned for the first time.

PMID- 22482547
TI  - Time-slice velocity-map ion imaging studies of the photodissociation of NO in the
      vacuum ultraviolet region.
AB  - The time-slice velocity-map ion imaging and the resonant four-wave mixing
      techniques are combined to study the photodissociation of NO in the vacuum
      ultraviolet (VUV) region around 13.5 eV above the ionization potential. The
      neutral atoms, i.e., N((2)D(o)), O((3)P(2)), O((3)P(1)), O((3)P(0)), and
      O((1)D(2)), are probed by exciting an autoionization line of O((1)D(2)) or
      N((2)D(o)), or an intermediate Rydberg state of O((3)P(0,1,2)). Old and new
      autoionization lines of O((1)D(2)) and N((2)D(o)) in this region have been
      measured and newer frequencies are given for them. The photodissociation channels
      producing N((2)D(o)) + O((3)P), N((2)D(o)) + O((1)D(2)), N((2)D(o)) + O((1)S(0)),
      and N((2)P(o)) + O((3)P) have all been identified. This is the first time that a
      single VUV photon has been used to study the photodissociation of NO in this
      energy region. Our measurements of the angular distributions show that the recoil
      anisotropy parameters (beta) for all the dissociation channels except for the
      N((2)D(o)) + O((1)S(0)) channel are minus at each of the wavelengths used in the
      present study. Thus direct excitation of NO by a single VUV photon in this energy
      region leads to excitation of states with Sigma or Delta symmetry (DeltaOmega =
      +/-1), explaining the observed perpendicular transition.

PMID- 22482548
TI  - Ultrafast structural and isomerization dynamics in the Rydberg-exited
      quadricyclane: norbornadiene system.
AB  - The quadricyclane-norbornadiene system is an important model for the
      isomerization dynamics between highly strained molecules. In a breakthrough
      observation for a polyatomic molecular system of that complexity, we follow the
      photoionization from Rydberg states in the time-domain to derive a measure for
      the time-dependent structural dynamics and the time-evolving structural
      dispersion even while the molecule is crossing electronic surfaces. The
      photoexcitation to the 3s and 3p Rydberg states deposits significant amounts of
      energy into vibrational motions. We observe the formation and evolution of the
      vibrational wavepacket on the Rydberg surface and the internal conversion from
      the 3p Rydberg states to the 3s state. In that state, quadricyclane isomerizes to
      norbornadiene with a time constant of tau(2) = 136(45) fs. The lifetime of the 3p
      Rydberg state in quadricyclane is tau(1) = 320(31) and the lifetime of the 3s
      Rydberg state in norbornadiene is tau(3) = 394(32).

PMID- 22482549
TI  - Active control of the lifetime of excited resonance states by means of laser
      pulses.
AB  - Quantum control of the lifetime of a system in an excited resonance state is
      investigated theoretically by creating coherent superpositions of overlapping
      resonances. This control scheme exploits the quantum interference occurring
      between the overlapping resonances, which can be controlled by varying the width
      of the laser pulse that creates the superposition state. The scheme is applied to
      a realistic model of the Br(2)(B)-Ne predissociation decay dynamics through a
      three-dimensional wave packet method. It is shown that extensive control of the
      system lifetime is achievable, both enhancing and damping it remarkably. An
      experimental realization of the control scheme is suggested.

PMID- 22482550
TI  - Explicitly correlated Gaussian calculations of the 2P(o) Rydberg spectrum of the
      lithium atom.
AB  - Accurate quantum-mechanical nonrelativistic variational calculations are
      performed for the nine lowest members of the (2)P(o) Rydberg series (1s(2)np(1),
      n = 2, ..., 10) of the lithium atom. The effect of the finite nuclear mass is
      included in the calculations allowing for determining the isotopic shifts of the
      energy levels. The wave functions of the states are expanded in terms of all
      electron explicitly correlated Gaussian functions. The exponential parameters of
      the Gaussians are variationally optimized with the aid of the analytical energy
      gradient determined with respect to those parameters. The calculated state
      energies are compared with the available experimental data.

PMID- 22482551
TI  - Computational study of the rovibrational spectrum of (OCS)2.
AB  - In this paper, we report a new intermolecular potential energy surface and
      rovibrational transition frequencies and line strengths computed for the OCS
      dimer. The potential is made by fitting energies obtained from explicitly
      correlated coupled-cluster calculations and fit using an interpolating moving
      least squares method. The rovibrational Schroedinger equation is solved with a
      symmetry-adapted Lanczos algorithm and an uncoupled product basis set. All four
      intermolecular coordinates are included in the calculation. On the potential
      energy surface we find, previously unknown, cross-shaped isomers and also polar
      and non-polar isomers. The associated wavefunctions and energy levels are
      presented. To identify polar and cross states we use both calculations of line
      strengths and vibrational parent analysis. Calculated rotational constants differ
      from their experimental counterparts by less than 0.001 cm(-1).

PMID- 22482552
TI  - Absolute photoionization cross-section of the propargyl radical.
AB  - Using synchrotron-generated vacuum-ultraviolet radiation and multiplexed time
      resolved photoionization mass spectrometry we have measured the absolute
      photoionization cross-section for the propargyl (C(3)H(3)) radical,
      sigma(propargyl) (ion)(E), relative to the known absolute cross-section of the
      methyl (CH(3)) radical. We generated a stoichiometric 1:1 ratio of C(3)H(3):CH(3)
      from 193 nm photolysis of two different C(4)H(6) isomers (1-butyne and 1,3
      butadiene). Photolysis of 1-butyne yielded values of sigma(propargyl)(ion)(10.213
      eV)=(26.1+/-4.2) Mb and sigma(propargyl)(ion)(10.413 eV)=(23.4+/-3.2) Mb, whereas
      photolysis of 1,3-butadiene yielded values of sigma(propargyl)(ion)(10.213
      eV)=(23.6+/-3.6) Mb and sigma(propargyl)(ion)(10.413 eV)=(25.1+/-3.5) Mb. These
      measurements place our relative photoionization cross-section spectrum for
      propargyl on an absolute scale between 8.6 and 10.5 eV. The cross-section derived
      from our results is approximately a factor of three larger than previous
      determinations.

PMID- 22482553
TI  - C-C bond unsaturation degree in monosubstituted ferrocenes for molecular
      electronics investigated by a combined near-edge x-ray absorption fine structure,
      x-ray photoemission spectroscopy, and density functional theory approach.
AB  - We present the results of an experimental and theoretical investigation of
      monosubstituted ethyl-, vinyl-, and ethynyl-ferrocene (EtFC, VFC, and EFC) free
      molecules, obtained by means of synchrotron-radiation based C 1s photoabsorption
      (NEXAFS) and photoemission (C 1s XPS) spectroscopies, and density functional
      theory (DFT) calculations. Such a combined study is aimed at elucidating the role
      played by the C-C bond unsaturation degree of the substituent on the electronic
      structure of the ferrocene derivatives. Such substituents are required for
      molecular chemical anchoring onto relevant surfaces when ferrocenes are used for
      molecular electronics hybrid devices. The high resolution C 1s NEXAFS spectra
      exhibit distinctive features that depend on the degree of unsaturation of the
      hydrocarbon substituent. The theoretical approach to consider the NEXAFS spectrum
      made of three parts allowed to disentangle the specific contribution of the
      substituent group to the experimental spectrum as a function of its unsaturation
      degree. C 1s IEs were derived from the experimental data analysis based on the
      DFT calculated IE values for the different carbon atoms of the substituent and
      cyclopentadienyl (Cp) rings. Distinctive trends of chemical shifts were observed
      for the substituent carbon atoms and the substituted atom of the Cp ring along
      the series of ferrocenes. The calculated IE pattern was rationalized in terms of
      initial and final state effects influencing the IE value, with special regard to
      the different mechanism of electron conjugation between the Cp ring and the
      substituent, namely the sigma/pi hyperconjugation in EtFC and the pi-conjugation
      in VFC and EFC.

PMID- 22482554
TI  - Two-dimensional laser induced fluorescence spectroscopy of van der Waals
      complexes: fluorobenzene-Ar(n) (n = 1,2).
AB  - The technique of two-dimensional laser induced fluorescence (2D-LIF) spectroscopy
      has been used to observe the van der Waals complexes fluorobenzene-Ar and
      fluorobenzene-Ar(2) in the region of their S(1)-S(0) electronic origins. The 2D
      LIF spectral images reveal a number of features assigned to the van der Waals
      vibrations in S(0) and S(1). An advantage of 2D-LIF spectroscopy is that the LIF
      spectrum associated with a particular species may be extracted from an image.
      This is illustrated for fluorobenzene-Ar. The S(1) van der Waals modes observed
      in this spectrum are consistent with previous observations using mass resolved
      resonance enhanced multiphoton ionisation techniques. For S(0), the two bending
      modes previously observed using a Raman technique were observed along with three
      new levels. These agree exceptionally well with ab initio calculations. The Fermi
      resonance between the stretch and bend overtone has been analysed in both the
      S(0) and S(1) states, revealing that the coupling is stronger in S(0) than in
      S(1). For fluorobenzene-Ar(2) the 2D-LIF spectral image reveals the S(0)
      symmetric stretch van der Waals vibration to be 35.0 cm(-1), closely matching the
      value predicted based on the fluorobenzene-Ar van der Waals stretch frequency.
      Rotational band contour analysis has been performed on the fluorobenzene-Ar
      0(0)(0) transition to yield a set of S(1) rotational constants A' = 0.05871 +/-
      0.00014 cm(-1), B' = 0.03803 +/- 0.00010 cm(-1), and C' = 0.03103 +/- 0.00003 cm(
      1). The rotational constants imply that in the S(1) 0(0) level the Ar is on
      average 3.488 A from the fluorobenzene centre of mass and displaced from it
      towards the centre of the ring at an angle of ~6 degrees  to the normal. The
      rotational contour for fluorobenzene-Ar(2) was predicted using rotational
      constants calculated on the basis of the fluorobenzene-Ar geometry and compared
      with the experimental contour. The comparison is poor which, while due in part to
      expected saturation effects, suggests the presence of another band lying beneath
      the contour.

PMID- 22482555
TI  - Electronic states and pseudo Jahn-Teller distortion of heavy metal-monobenzene
      complexes: M(C6H6) (M = Y, La, and Lu).
AB  - Monobenzene complexes of yttrium (Y), lanthanum (La), and lutetium (Lu),
      M(C(6)H(6)) (M = Y, La, and Lu), were prepared in a laser-vaporization supersonic
      molecular beam source and studied by pulsed-field ionization zero electron
      kinetic energy (ZEKE) spectroscopy and ab initio calculations. The calculations
      included the second-order perturbation, the coupled cluster with single, double,
      and perturbative triple excitation, and the complete active space self-consistent
      field methods. Adiabatic ionization energies and metal-benzene stretching
      frequencies of these complexes were measured for the first time from the ZEKE
      spectra. Electronic states of the neutral and ion complexes and benzene ring
      deformation were determined by combining the spectroscopic measurements with the
      theoretical calculations. The ionization energies of M(C(6)H(6)) are 5.0908 (6),
      4.5651 (6), and 5.5106 (6) eV, and the metal-ligand stretching frequencies of
      [M(C(6)H(6))](+) are 328, 295, and 270 cm(-1) for M = Y, La, and Lu,
      respectively. The ground states of M(C(6)H(6)) and [M(C(6)H(6))](+) are (2)A(1)
      and (1)A(1), respectively, and their molecular structures are in C(2v) point
      group with a bent benzene ring. The deformation of the benzene ring upon metal
      coordination is caused by the pseudo Jahn-Teller interaction of
      (1(2)E(2)+1(2)A(1)+2(2)E(2)) e(2) at C(6v) symmetry. In addition, the study shows
      that spectroscopic behaviors of Y(C(6)H(6)) and La(C(6)H(6)) are similar to each
      other, but different from that of Lu(C(6)H(6)).

PMID- 22482556
TI  - Metallic and molecular orbital concepts in XMg8 clusters, X = Be-F.
AB  - The electronic structure and stability of the XMg(8) clusters (X = Be, B, C, N,
      O, and F) are studied using first principles theoretical calculations to
      understand the variation in bonding in heteroatomic clusters which mix simple
      divalent metals with main group dopants. We examine these progressions with two
      competing models, the first is a distorted nearly free electron gas model and the
      second is a molecular orbital picture examining the orbital overlap between the
      dopant and the cluster. OMg(8) is found to be the most energetically stable
      cluster due to strong bonding of O with the Mg(8) cluster. BeMg(8) has the
      largest HOMO-LUMO gap due to strong hybridization between the Mg(8) and the Be
      dopant states that form a delocalized pool of 18 valence electrons with a closed
      electronic shell due to crystal field effects. Be, B, and C are best described by
      the nearly free electron gas model, while N, O, and F are best described through
      molecular orbital concepts.

PMID- 22482557
TI  - Ground and low-lying excited states of propadienylidene (H2C=C=C:) obtained by
      negative ion photoelectron spectroscopy.
AB  - A joint experimental-theoretical study has been carried out on electronic states
      of propadienylidene (H(2)CCC), using results from negative-ion photoelectron
      spectroscopy. In addition to the previously characterized X(1)A(1) electronic
      state, spectroscopic features are observed that belong to five additional states:
      the low-lying a(3)B(1) and b(3)A(2) states, as well as two excited singlets,
      A(1)A(2) and B(1)B(1), and a higher-lying triplet, c(3)A(1). Term energies (T(0),
      in cm(-1)) for the excited states obtained from the data are: 10,354+/-11
      (a(3)B(1)); 11,950+/-30 (b(3)A(2)); 20,943+/-11 (c(3)A(1)); and 13,677+/-11
      (A(1)A(2)). Strong vibronic coupling affects the A(1)A(2) and B(1)B(1) states as
      well as a(3)B(1) and b(3)A(2) and has profound effects on the spectrum. As a
      result, only a weak, broadened band is observed in the energy region where the
      origin of the B(1)B(1) state is expected. The assignments here are supported by
      high-level coupled-cluster calculations and spectral simulations based on a
      vibronic coupling Hamiltonian. A result of astrophysical interest is that the
      present study supports the idea that a broad absorption band found at 5450 A by
      cavity ringdown spectroscopy (and coincident with a diffuse interstellar band) is
      carried by the B(1)B(1) state of H(2)CCC.

PMID- 22482558
TI  - Elastic cross sections for electron scattering from GeF4: predominance of atomic
      F in the high-energy collision dynamics.
AB  - We report absolute differential cross sections (DCSs) for elastic electron
      scattering from GeF(4). The incident electron energy range was 3-200 eV, while
      the scattered electron angular range was typically 15 degrees -150 degrees . In
      addition, corresponding independent atom model (IAM) calculations, within the
      screened additivity rule (SCAR) formulation, were also performed. Those results,
      particularly for electron energies above about 10 eV, were found to be in good
      quantitative agreement with the present experimental data. Furthermore, we
      compare our GeF(4) elastic DCSs to similar data for scattering from CF(4) and
      SiF(4). All these three species possess T(d) symmetry, and at each specific
      energy considered above about 50 eV their DCSs are observed to be almost
      identical. These indistinguishable features suggest that high-energy elastic
      scattering from these targets is virtually dominated by the atomic-F species of
      the molecules. Finally, estimates for the measured GeF(4) elastic integral cross
      sections are derived and compared to our IAM-SCAR computations and with
      independent total cross section values.

PMID- 22482559
TI  - Stark spectrum simulation for X2Y4 molecules: application to the nu12 band of
      ethylene in a high-silica zeolite.
AB  - The influence of an electric field of silicalite-1-zeolite on the FTIR
      vibrational absorption spectrum of ethylene has been simulated and compared to
      experimental spectra. The presence of silicalite-1 produces a global shift and a
      change of the structure of vibrational bands. To explain the global shift of the
      nu(12) band (CH(2) scissor mode) and therefore to estimate an effective average
      field produced by silicalite-1, Stark calculations were performed. These
      calculations were based on a tensorial formalism implemented in the D(2h)TDS-ST
      package [M. Sanzharov, M. Rotger, C. Wenger, M. Loete, V. Boudon, and A. Rouzee,
      J. Quant. Spectrosc. Radiat. Transf. 112, 41 (2011)]. The value of the field
      obtained using tensorial formalism (8-11 GV/m) is compared with values obtained
      using ab initio calculations. A theory of the molecular alignment in the electric
      field using tensorial formalism is also developed to model the interaction of
      ethylene in contact with a zeolite environment.

PMID- 22482560
TI  - Magnetic structure variation in manganese-oxide clusters.
AB  - Negative-ion photoelectron spectroscopy and ab initio simulations are used to
      study the variation in magnetic structure in Mn(x)O(y) (x = 3, 4[semicolon] y =
      1, 2) clusters. The ferrimagnetic and antiferromagnetic ground-state structures
      of Mn(x)O(y) are 0.16-1.20 eV lower in energy than their ferromagnetic isomers.
      The presence of oxygen thus stabilizes low-spin isomers relative to the preferred
      high-spin ordering of bare Mn(3) and Mn(4). Each cluster has a preferred overall
      magnetic moment, and no evidence is seen of competing states with different spin
      multiplicities. However, non-degenerate isomags, which possess the same spin
      multiplicity but different arrangements of local moments, do contribute
      additional features and peak broadening in the photoelectron spectra. Proper
      accounting for all possible isomags is shown to be critical for accurate
      computational prediction of the spectra.

PMID- 22482561
TI  - Infrared spectroscopy of carbonyl sulfide inside a pure 3He droplet.
AB  - The infrared spectrum of the nu(3) band of an OCS (carbonyl sulfide) molecule
      embedded inside pure (3)He droplets of about 12 * 10(3) atoms reported in 1998
      [S. Grebenev, J. P. Toennies, and A. F. Vilesov, Science 279, 2083 (1998)] is
      carefully evaluated. The spectrum, which consists of a broad central peak and a
      distinct shoulder at lower energy, was analyzed by assuming unresolved rotational
      line structure of either a linear or a symmetric top. In each case the spectrum
      was fitted using either Lorentzian or Gaussian peak shapes with a preassigned
      fixed temperature of 0.15 K or a best fit temperature. Many of the fits describe
      the spectra nearly equally well and indicate broad R(0), R(1), and P(1) peaks but
      no Q-branch, a moment of inertia which is about a factor six greater than for the
      free molecule, and a temperature of 0.07 +/- 0.06 K which is significantly less
      than 0.15 K determined for mixed (3)He/(4)He droplets. The increased moment of
      inertia is consistent with about 11 attached (3)He atoms which take part in the
      end-over-end rotations of the chromophore. The large line widths are attributed
      to creation of particle-hole pair excitations in the fermionic droplets.

PMID- 22482562
TI  - Theoretical predictions of properties of group-2 elements including element 120
      and their adsorption on noble metal surfaces.
AB  - Trends in properties of group-2 elements Ca through element 120 and their M(2)
      and MAu dimers were determined on the basis of atomic and molecular relativistic
      density functional theory calculations. The relativistic contraction and
      stabilization of the ns AO with increasing atomic number were shown to result in
      the inversion of trends both in atomic and molecular properties in group 2 beyond
      Ba, so that element 120 should be chemically similar to Sr. Due to the same
      reason, bonding in (120)(2) and 120Au should be the weakest among the considered
      here M(2) and MAu. Using calculated dissociation energies of M(2), the
      sublimation enthalpy, DeltaH(sub), of element 120 of 150 kJ/mol was estimated via
      a correlation between these quantities in group 2. Using the M-Au binding
      energies, the adsorption enthalpies, DeltaH(ads), of element 120 of 172 kJ/mol on
      gold, 127 kJ/mol on platinum, and 50 kJ/mol on silver were estimated via a
      correlation with known DeltaH(ads) in the group. These moderate values of
      DeltaH(ads) are indicative of a possibility of chromatography adsorption studies
      of element 120 on these noble metal surfaces.

PMID- 22482563
TI  - Structural characterization of electron-induced proton transfer in the formic
      acid dimer anion, (HCOOH)2-, with vibrational and photoelectron spectroscopies.
AB  - The (HCOOH)(2) anion, formed by electron attachment to the formic acid dimer
      (FA(2)), is an archetypal system for exploring the mechanics of the electron
      induced proton transfer motif that is purported to occur when neutral nucleic
      acid base-pairs accommodate an excess electron [K. Aflatooni, G. A. Gallup, and
      P. D. Burrow, J. Phys. Chem. A 102, 6205 (1998); J. H. Hendricks, S. A.
      Lyapustina, H. L. de Clercq, J. T. Snodgrass, and K. H. Bowen, J. Chem Phys. 104,
      7788 (1996); C. Desfrancois, H. Abdoul-Carime, and J. P. Schermann, ibid. 104,
      7792 (1996)]. The FA(2) anion and several of its H/D isotopologues were isolated
      in the gas phase and characterized using Ar-tagged vibrational predissociation
      and electron autodetachment spectroscopies. The photoelectron spectrum of the
      FA(2) anion was also recorded using velocity-map imaging. The resulting
      spectroscopic information verifies the equilibrium FA(2)(-) geometry predicted by
      theory which features a symmetrical, double H-bonded bridge effectively linking
      together constituents that most closely resemble the formate ion and a
      dihydroxymethyl radical. The spectroscopic signatures of this ion were analyzed
      with the aid of calculated anharmonic vibrational band patterns.

PMID- 22482564
TI  - The H + Li2 bimolecular exchange reaction: dynamical and kinetical properties at
      J = 0.
AB  - For the first time in the literature, rigorous time-independent quantum
      scattering formalism was applied, by means of the ABC program, to the H + Li(2) 
      > LiH + Li reaction. The state-to-state probabilities as a function of the total
      energy have been computed at zero total angular momentum (J = 0) allowing us to
      evaluate the effect of vibrational/rotational excitation on the reaction
      promotion/inhibition, the energetic distribution of products, and the temperature
      dependence of the J-shifting thermal rate coefficients.

PMID- 22482565
TI  - Thermally induced polarizabilities and dipole moments of small tin clusters.
AB  - We study the influence of thermal excitation on the electric susceptibilities for
      Sn(6) and Sn(7) clusters by molecular beam electric deflection and Monte-Carlo
      simulations in conjunction with quantum-chemical calculations. At low
      temperatures (40 K), no field-induced broadening of the Sn(6) and Sn(7) cluster
      beams are observed, in agreement with vanishing permanent electric dipole moments
      due to their centro-symmetrical ground states. The electric polarizabilities of
      Sn(6) and Sn(7), as inferred from the field-induced molecular beam deflection,
      are in good agreement with the quantum-chemical predictions. At elevated
      temperatures of 50-100 K, increased polarizabilities of about 2-3 A(3) are
      obtained. Also, we found indications of a field-induced beam broadening which
      points to the existence of permanent dipole moments of about 0.01-0.02 D per atom
      at higher temperatures. These results cannot be explained by thermal excitations
      within a harmonic oscillator model, which would yield a temperature-independent
      polarizability and fluxional, but not permanent, dipole moments. We analyze this
      behavior by Monte-Carlo simulations in order to compute average temperature
      induced electric dipole moments. For that purpose, we developed a novel technique
      for predicting observables sampled on the quantum-chemical potential energy
      surface by an umbrella sampling correction of Monte-Carlo results obtained from
      simulations utilizing an empirical potential. The calculated, fluxional dipole
      moments are in tune with the observed beam broadenings. The cluster dynamics
      underlying the polarizability appear to be intermediate between rigid and floppy
      molecules which leads to the conclusion that the rotational, not the vibrational
      temperature seems to be the key parameter that determines the temperature
      dependence of the polarizability.

PMID- 22482566
TI  - Amplification of the linear and nonlinear optical response of a chiral molecular
      crystal.
AB  - We have observed large second-order nonlinear optical and vibrational circular
      dichroism (VCD) responses in a charge-transfer-type L-Histidinium salt. Using X
      ray Diffraction, VCD spectroscopy, and time-dependent density functional theory
      to characterize the compound, we employ a two-level model to explain and quantify
      the strongly enhanced optical signals. We find that both linear and nonlinear
      optical responses are greatly enhanced by a single low-lying charge-transfer
      state.

PMID- 22482567
TI  - Nucleation of colloids and macromolecules: does the nucleation pathway matter?
AB  - A recent description of diffusion-limited nucleation based on fluctuating
      hydrodynamics that extends classical nucleation theory predicts a very non
      classical two-step scenario whereby nucleation is most likely to occur in
      spatially extended, low-amplitude density fluctuations. In this paper, it is
      shown how the formalism can be used to determine the maximum probability of
      observing any proposed nucleation pathway, thus allowing one to address the
      question as to their relative likelihood, including of the newly proposed pathway
      compared to classical scenarios. Calculations are presented for the nucleation of
      high-concentration droplets in a low-concentration solution of globular proteins
      and it is found that the relative probabilities (new theory compared to classical
      result) for reaching a critical nucleus containing N(c) molecules scales as e(
      N(c)/3) thus indicating that for all but the smallest nuclei, the classical
      scenario is extremely unlikely.

PMID- 22482568
TI  - Absence of photoemission from the Fermi level in potassium intercalated picene
      and coronene films: structure, polaron, or correlation physics?
AB  - The electronic structure of potassium intercalated picene and coronene films has
      been studied using photoemission spectroscopy. Picene has additionally been
      intercalated using sodium. Upon alkali metal addition core level as well as
      valence band photoemission data signal a filling of previously unoccupied states
      of the two molecular materials due to charge transfer from potassium. In contrast
      to the observation of superconductivity in K(x)picene and K(x)coronene (x ~ 3),
      none of the films studied shows emission from the Fermi level, i.e., we find no
      indication for a metallic ground state. Several reasons for this observation are
      discussed.

PMID- 22482569
TI  - Geometry and the entropic cost of locally favoured structures in a liquid.
AB  - The role of the geometry of locally favoured structures in an equilibrium liquid
      is analyzed within a recently developed lattice model. The local geometry is
      shown to influence the liquid through the entropy and the associated density of
      states. We show that favoured local structures with low symmetry will, generally,
      incur a low entropy cost and, as a consequence, the liquid will exhibit a
      substantial accumulation of these low energy environments on cooling prior to the
      freezing transition.

PMID- 22482570
TI  - Revisiting the phase diagram of hard ellipsoids.
AB  - In this work, the well-known Frenkel-Mulder phase diagram of hard ellipsoids of
      revolution [D. Frenkel and B. M. Mulder, Mol. Phys. 55, 1171 (1985)] is revisited
      by means of replica exchange Monte Carlo simulations. The method provides good
      sampling of dense systems and so, solid phases can be accessed without the need
      of imposing a given structure. At high densities, we found plastic solids and fcc
      like crystals for semi-spherical ellipsoids (prolates and oblates), and SM2
      structures [P. Pfleiderer and T. Schilling, Phys. Rev. E 75, 020402 (2007)] for x
      : 1-prolates and 1 : x-oblates with x >= 3. The revised fluid-crystal and
      isotropic-nematic transitions reasonably agree with those presented in the
      Frenkel-Mulder diagram. An interesting result is that, for small system sizes
      (100 particles), we obtained 2:1- and 1.5:1-prolate equations of state without
      transitions, while some order is developed at large densities. Furthermore, the
      symmetric oblate cases are also reluctant to form ordered phases.

PMID- 22482571
TI  - Effect of charge asymmetry and charge screening on structure of superlattices
      formed by oppositely charged colloidal particles.
AB  - Colloidal suspensions made up of oppositely charged particles have been shown to
      self-assemble into substitutionally ordered superlattices. For a given colloidal
      suspension, the structure of the superlattice formed from self-assembly depends
      on its composition, charges on the particles, and charge screening. In this study
      we have computed the pressure-composition phase diagrams of colloidal suspensions
      made up of binary mixtures of equal sized and oppositely charged particles
      interacting via hard core Yukawa potential for varying values of charge screening
      and charge asymmetry. The systems are studied under conditions where the thermal
      energy is equal or greater in magnitude to the contact energy of the particles
      and the Debye screening length is smaller than the size of the particles. Our
      studies show that charge asymmetry has a significant effect on the ability of
      colloidal suspensions to form substitutionally ordered superlattices. Slight
      deviations of the charges from the stoichiometric ratio are found to drastically
      reduce the thermodynamic stability of substitutionally ordered superlattices.
      These studies also show that for equal-sized particles, there is an optimum
      amount of charge screening that favors the formation of substitutionally ordered
      superlattices.

PMID- 22482572
TI  - A phenomenological approach to modeling chemical dynamics in nonlinear and two
      dimensional spectroscopy.
AB  - We present an approach for calculating nonlinear spectroscopic observables, which
      overcomes the approximations inherent to current phenomenological models without
      requiring the computational cost of performing molecular dynamics simulations.
      The trajectory mapping method uses the semi-classical approximation to linear and
      nonlinear response functions, and calculates spectra from trajectories of the
      system's transition frequencies and transition dipole moments. It rests on
      identifying dynamical variables important to the problem, treating the dynamics
      of these variables stochastically, and then generating correlated trajectories of
      spectroscopic quantities by mapping from the dynamical variables. This approach
      allows one to describe non-Gaussian dynamics, correlated dynamics between
      variables of the system, and nonlinear relationships between spectroscopic
      variables of the system and the bath such as non-Condon effects. We illustrate
      the approach by applying it to three examples that are often not adequately
      treated by existing analytical models--the non-Condon effect in the nonlinear
      infrared spectra of water, non-Gaussian dynamics inherent to strongly hydrogen
      bonded systems, and chemical exchange processes in barrier crossing reactions.
      The methods described are generally applicable to nonlinear spectroscopy
      throughout the optical, infrared and terahertz regions.

PMID- 22482573
TI  - Mechanism of densification in silica glass under pressure as revealed by a bottom
      up pairwise effective interaction model.
AB  - A new short-range pairwise numerical potential for silica is presented. The
      potential is derived from a single ab initio molecular dynamics (AIMD) simulation
      of molten silica using the force-matching method with the forces being
      represented numerically by piecewise functions (splines). The AIMD simulation is
      performed using the Born-Oppenheimer method with the generalized gradient
      approximation (BLYP) for the XC energy functional. The new effective potential
      includes a soft-repulsive shoulder to describe the interactions of oxygen ions at
      short separations. The new potential, despite being short-ranged and derived from
      single-phase data, exhibits a good transferability to silica crystalline
      polymorphs and amorphous silica. The importance of the O-O soft-repulsive
      shoulder interaction on glass densification under cold and shock compressions is
      assessed from MD simulations of silica glass under room and shock Hugoniot
      conditions, respectively. Results from these simulations indicate that the
      appearance of oxygen complexes (primarily pairs) interacting through soft
      repulsive shoulder potential occurs at 8-10 GPa, and under cold compression
      conditions becomes notable at 40 GPa, essentially coinciding with the transition
      to a Si sixfold coordination state. An analysis of changes in system structure in
      compressed and shocked states reveals that the O ions interacting through the
      soft-repulsive shoulder potential in denser states of silica glass may create a
      mechanical multi-stability under elevated pressures and thus to contribute to the
      observed anomalous densification.

PMID- 22482574
TI  - Low energy charged particles interacting with amorphous solid water layers.
AB  - The interaction of charged particles with condensed water films has been studied
      extensively in recent years due to its importance in biological systems, ecology
      as well as interstellar processes. We have studied low energy electrons (3-25 eV)
      and positive argon ions (55 eV) charging effects on amorphous solid water (ASW)
      and ice films, 120-1080 ML thick, deposited on ruthenium single crystal under
      ultrahigh vacuum conditions. Charging the ASW films by both electrons and
      positive argon ions has been measured using a Kelvin probe for contact potential
      difference (CPD) detection and found to obey plate capacitor physics. The
      incoming electrons kinetic energy has defined the maximum measurable CPD values
      by retarding further impinging electrons. L-defects (shallow traps) are suggested
      to be populated by the penetrating electrons and stabilize them. Low energy
      electron transmission measurements (currents of 0.4-1.5 MUA) have shown that the
      maximal and stable CPD values were obtained only after a relatively slow change
      has been completed within the ASW structure. Once the film has been stabilized,
      the spontaneous discharge was measured over a period of several hours at 103 +/-
      2 K. Finally, UV laser photo-emission study of the charged films has suggested
      that the negative charges tend to reside primarily at the ASW-vacuum interface,
      in good agreement with the known behavior of charged water clusters.

PMID- 22482575
TI  - Two-dimensional order-disorder transition of argon monolayer adsorbed on
      graphitized carbon black: kinetic Monte Carlo method.
AB  - We present results of application of the kinetic Monte Carlo technique to
      simulate argon adsorption on a graphite surface at temperatures below and above
      the triple point. We show that below the triple point the densification of the
      adsorbed layer with loading results in the rearrangement of molecules to form a
      hexagonal structure, which is accompanied by the release of an additional heat,
      associated with this disorder-order transition. This appears as a spike in the
      plot of the heat of adsorption versus loading at the completion of a monolayer on
      the surface. To describe the details of the adsorbed phase, we analyzed
      thermodynamic properties and the effects of temperature on the order-disorder
      transition of the first layer.

PMID- 22482576
TI  - Charge transfer and formation of reduced Ce3+ upon adsorption of metal atoms at
      the ceria (110) surface.
AB  - The modification of cerium dioxide with nanoscale metal clusters is intensely
      researched for catalysis applications, with gold, silver, and copper having been
      particularly well studied. The interaction of the metal cluster with ceria is
      driven principally by a localised interaction between a small number of metal
      atoms (as small as one) and the surface and understanding the fundamentals of the
      interaction of metal atoms with ceria surfaces is therefore of great interest.
      Much attention has been focused on the interaction of metals with the (111)
      surface of ceria, since this is the most stable surface and can be grown as
      films, which are probed experimentally. However, nanostructures exposing other
      surfaces such as (110) show high activity for reactions including CO oxidation
      and require further study; these nanostructures could be modified by deposition
      of metal atoms or small clusters, but there is no information to date on the
      atomic level details of metal-ceria interactions involving the (110) surface.
      This paper presents the results of density functional theory (DFT) corrected for
      on-site Coulomb interactions (DFT+U) calculations of the adsorption of a number
      of different metal atoms at an extended ceria (110) surface; the metals are Au,
      Ag, Cu, Al, Ga, In, La, Ce, V, Cr, and Fe. Upon adsorption all metals are
      oxidised, transferring electron(s) to the surface, resulting in localised surface
      distortions. The precise details depend on the identity of the metal atom. Au,
      Ag, Cu each transfer one electron to the surface, reducing one Ce ion to Ce(3+),
      while of the trivalent metals, Al and La are fully oxidised, but Ga and In are
      only partially oxidised. Ce and the transition metals are also partially
      oxidised, with the number of reduced Ce ions possible in this surface no more
      than three per adsorbed metal atom. The predicted oxidation states of the
      adsorbed metal atoms should be testable in experiments on ceria nanostructures
      modified with metal atoms.

PMID- 22482577
TI  - Performance of the M11-L density functional for bandgaps and lattice constants of
      unary and binary semiconductors.
AB  - The recently developed SOGGA11 and M11-L density functionals have been tested for
      the prediction of bandgaps and lattice constants by comparing to databases
      containing 31 bandgaps and 34 lattice constants. To make a comparative assessment
      we also test several other density functionals against the same databases; in
      particular, we test the local spin density approximation, PBE, PBEsol, SOGGA,
      TPSS, revTPSS, and M06-L local density functionals and the HSE screened-exchange
      hybrid nonlocal density functional; and for a subset of 13 lattice constants we
      also compare the mean errors to those of the AM05 and WC local density
      functionals and the HISS and HSEsol nonlocal density functionals. The tests show
      that, of the ten functionals tested against all 65 data, the SOGGA, PBEsol, and
      HSE functionals are the most accurate for lattice constants, whereas the HSE, M11
      L, and M06-L density functionals are the most accurate for bandgaps. However, the
      SOGGA11 density functional is the most accurate generalized gradient
      approximation for bandgaps.

PMID- 22482578
TI  - Pressure dependence of confined liquid behavior subjected to boundary-driven
      shear.
AB  - Non-equilibrium molecular dynamics simulations of boundary-driven sheared Lennard
      Jones liquids at variable pressure up to 5 GPa (for argon) reveal a rich out-of
      equilibrium phase behavior with a strong degree of shear localization. At the
      lowest apparent shear rate considered (wall speed ~1 m s(-1)) the confined region
      is an homogeneously sheared solid (S) with no slip at the walls. This transforms
      at higher shear rates to a non-flowing plug with slip at the walls, referred to
      as the plug slip (PS) state. At higher shear rate a central localized (CL) state
      formed in which the shear gradient was localized in the center of the film, with
      the rest of the confined sample in a crystalline state commensurate with the wall
      lattice. The central zone liquidlike region increased in width with shear rate. A
      continuous rounded temperature profile across the whole system reflects strong
      dynamical coupling between the wall and confined region. The temperature rise in
      the confined film is consistent with the Brinkman number. The transition from the
      PS to CL states typically occurred at a wall speed near where the shear stress
      approached a critical value of ~3% of the shear modulus, and also near the peak
      in the traction coefficient, MU. The peak traction coefficient values computed,
      ~0.12-0.14 at 1000 MPa agree with those found for traction fluids and occur when
      the confined liquid is in the PS and CL states. At low wall speeds slip can occur
      at one wall and stick at the other. Poorly wetting liquids manifest long-lived
      asymmetries in the confined liquid properties across the system, and a shift in
      solid-liquid phase co-existence to higher shear rates. A non-equilibrium phase
      diagram based on these results is proposed. The good agreement of the
      tribological response of the Lennard-Jones fluid with that of more complicated
      molecular systems suggests that a corresponding states scaling of the
      tribological behavior could apply.

PMID- 22482579
TI  - Vibrational properties of the compressed and the relaxed 1,4,5,8-naphthalene
      tetracarboxylic dianhydride monolayer on Ag(111).
AB  - Layers of 1,4,5,8-naphthalene-tetracarboxylic dianhydride (NTCDA) grown on
      Ag(111) at about 80 K have been investigated using Fourier transform infrared
      spectroscopy, spot profile analysis low-energy electron diffraction, and
      temperature programmed desorption. Specifically, the compressed and the relaxed
      monolayer, as well as the transformation between the two ordered phases have been
      analyzed in detail. It is found that the two monolayer phases display distinctly
      different vibrational spectra and can thus be discriminated with high accuracy
      and sensitivity. For the NTCDA/Ag(111) monolayer strong in-plane vibrational
      modes point at a marked dynamic charge transfer between molecule and metal
      substrate and provide clear evidence for an efficient electronic coupling to the
      Ag(111) surface in conjunction with a partially filled electronic level at the
      Fermi energy. The bilayer, on the other hand, is largely electronically decoupled
      from the substrate and, according to the vanishing infrared-active in-plane
      vibrational modes, is oriented parallel to the surface. On the basis of
      spectroscopic data the metastable nature of the bilayer phase is identified as
      such, leading to an improved understanding of processes encountered in the course
      of layer preparation and resolving inconsistencies reported in the literature.

PMID- 22482580
TI  - Reconciling lattice and continuum models for polymers at interfaces.
AB  - It is well known that lattice and continuum descriptions for polymers at
      interfaces are, in principle, equivalent. In order to compare the two models
      quantitatively, one needs a relation between the inverse extrapolation length c
      as used in continuum theories and the lattice adsorption parameter Deltachi(s)
      (defined with respect to the critical point). So far, this has been done only for
      ideal chains with zero segment volume in extremely dilute solutions. The relation
      Deltachi(s)(c) is obtained by matching the boundary conditions in the two models.
      For depletion (positive c and Deltachi(s)) the result is very simple: Deltachi(s)
      = ln(1 + c/5). For adsorption (negative c and Deltachi(s)) the ideal-chain
      treatment leads to an unrealistic divergence for strong adsorption: c decreases
      without bounds and the train volume fraction exceeds unity. This due to the fact
      that for ideal chains the volume filling cannot be accounted for. We extend the
      treatment to real chains with finite segment volume at finite concentrations, for
      both good and theta solvents. For depletion the volume filling is not important
      and the ideal-chain result Deltachi(s) = ln(1 + c/5) is generally valid also for
      non-ideal chains, at any concentration, chain length, or solvency. Depletion
      profiles can be accurately described in terms of two length scales: rho =
      tanh(2)[(z + p)/delta], where the depletion thickness (distal length) delta is a
      known function of chain length and polymer concentration, and the proximal length
      p is a known function of c (or Deltachi(s)) and delta. For strong repulsion p =
      1/c (then the proximal length equals the extrapolation length), for weaker
      repulsion p depends also on chain length and polymer concentration (then p is
      smaller than 1/c). In very dilute solutions we find quantitative agreement with
      previous analytical results for ideal chains, for any chain length, down to
      oligomers. In more concentrated solutions there is excellent agreement with
      numerical self-consistent depletion profiles, for both weak and strong repulsion,
      for any chain length, and for any solvency. For adsorption the volume filling
      dominates. As a result c now reaches a lower limit c ~ -0.5 (depending slightly
      on solvency). This limit follows immediately from the condition of a fully
      occupied train layer. Comparison with numerical SCF calculations corroborates
      that our analytical result is a good approximation. We suggest some simple
      methods to determine the interaction parameter (either c or Deltachi(s)) from
      experiments. The relation Deltachi(s)(c) provides a quantitative connection
      between continuum and lattice theories, and enables the use of analytical
      continuum results to describe the adsorption (and stretching) of lattice chains
      of any chain length. For example, a fully analytical treatment of mechanical
      desorption of a polymer chain (including the temperature dependence and the phase
      transitions) is now feasible.

PMID- 22482581
TI  - Scattering intensity of bicontinuous microemulsions and sponge phases.
AB  - Monte Carlo simulations of dynamically triangulated surfaces of variable topology
      are used to investigate the scattering intensities of bicontinuous
      microemulsions. The bulk scattering intensity is shown to follow the Teubner
      Strey expression. The domain size and the correlation length are extracted from
      the scattering peaks as a function of the bending rigidity, saddle-splay modulus,
      and surfactant density. The results are compared to earlier theories based on
      Ginzburg-Landau and Gaussian random field models. The ratio of the two length
      scales is shown to be well described by a linear combination of logarithmically
      renormalized bending rigidity and saddle-splay modulus with universal prefactors.
      This is in contrast to earlier theoretical predictions in which the scattering
      intensity is independent of the saddle-splay modulus. The equation of state, and
      the asymptotics of the bulk and film scattering intensities for high and low wave
      vectors are determined from simulations and compared with theoretical results.

PMID- 22482582
TI  - Thermal behavior of 1,2-dipalmitoyl-sn-3-phosphoglycerocholine bi- and multi
      layers, deposited with physical vapor deposition under ellipsometric growth
      control.
AB  - 1,2-dipalmitoyl-sn-3-phosphoglycerocholine membranes were deposited onto a
      silicon substrate (Si/SiO(2)) using physical vapor deposition with in situ
      ellipsometric thickness control. Along several heating cycles it was possible to
      identify well-defined boundaries for gel, ripple, liquid crystalline, and fluid
      disordered phases. Particularly, the second order transition between gel and
      ripple phase was clearly identified in the range of ~28-34  degrees C using Raman
      spectroscopy. Atomic force microscopy and imaging ellipsometry (IE) were used to
      observe and characterize the ripple phase undulations of period lambda = 20.8 nm
      and average height h = 19.95 nm along the temperature interval of ~34 to 40 
      degrees C. Clusters/agglomerations heights of more than twice the membrane
      thickness were observed with IE, induced by heating cycles.

PMID- 22482583
TI  - Simulation of fluid-solid coexistence in finite volumes: a method to study the
      properties of wall-attached crystalline nuclei.
AB  - The Asakura-Oosawa model for colloid-polymer mixtures is studied by Monte Carlo
      simulations at densities inside the two-phase coexistence region of fluid and
      solid. Choosing a geometry where the system is confined between two flat walls,
      and a wall-colloid potential that leads to incomplete wetting of the crystal at
      the wall, conditions can be created where a single nanoscopic wall-attached
      crystalline cluster coexists with fluid in the remainder of the simulation box.
      Following related ideas that have been useful to study heterogeneous nucleation
      of liquid droplets at the vapor-liquid coexistence, we estimate the contact
      angles from observations of the crystalline clusters in thermal equilibrium. We
      find fair agreement with a prediction based on Young's equation, using estimates
      of interface and wall tension from the study of flat surfaces. It is shown that
      the pressure versus density curve of the finite system exhibits a loop, but the
      pressure maximum signifies the "droplet evaporation-condensation" transition and
      thus has nothing in common with a van der Waals-like loop. Preparing systems
      where the packing fraction is deep inside the two-phase coexistence region, the
      system spontaneously forms a "slab state," with two wall-attached crystalline
      domains separated by (flat) interfaces from liquid in full equilibrium with the
      crystal in between; analysis of such states allows a precise estimation of the
      bulk equilibrium properties at phase coexistence.

PMID- 22482585
TI  - Computer simulation of linkage of two ring chains.
AB  - We performed off-lattice Monte Carlo simulations of links of two model ring
      chains with chain length N up to 32,768 in the theta solution or amorphous bulk
      state by using a random walk model (Model I), and molecular dynamics simulations
      of two model ring chains in solution with excluded volume interaction (Model II)
      to investigate topological effects on the geometry of link and ring conformation.
      In the case of Model I, the mean squared linking number, its distribution, and
      the size of two chains with fixed linking number are investigated. Our simulation
      results confirm the previous theoretical prediction that the mean squared linking
      number decays as pe(-qs(2)) with the distance of centers of chain mass s, where p
      and q are found to be chain length dependent and q asymptotically approaches to
      0.75 as chain length increases. The linking number distribution of two chains has
      a universal form for long chains, but our simulation results clearly show that
      the distribution function deviates from the Gaussian distribution, a fact not
      predicted by any previous theoretical work. A scaling prediction is proposed to
      predict the link size, and is checked for our simulations for the Model II. The
      simulation results confirmed the scaling prediction of the blob picture that the
      link with linking number m occupies a compact volume of m blobs, and the size of
      the link is asymptotic to R(L) ~ bN(nu)m(1/3-nu), where N is the chain length,
      and v is the Flory exponent of polymer in solutions.

PMID- 22482584
TI  - Theory of volume transition in polyelectrolyte gels with charge regularization.
AB  - We present a theory for polyelectrolyte gels that allow the effective charge of
      the polymer backbone to self-regulate. Using a variational approach, we obtain an
      expression for the free energy of gels that accounts for the gel elasticity, free
      energy of mixing, counterion adsorption, local dielectric constant, electrostatic
      interaction among polymer segments, electrolyte ion correlations, and self
      consistent charge regularization on the polymer strands. This free energy is then
      minimized to predict the behavior of the system as characterized by the gel
      volume fraction as a function of external variables such as temperature and salt
      concentration. We present results for the volume transition of polyelectrolyte
      gels in salt-free solvents, solvents with monovalent salts, and solvents with
      divalent salts. The results of our theoretical analysis capture the essential
      features of existing experimental results and also provide predictions for
      further experimentation. Our analysis highlights the importance of the self
      regularization of the effective charge for the volume transition of gels in
      particular, and for charged polymer systems in general. Our analysis also enables
      us to identify the dominant free energy contributions for charged polymer
      networks and provides a framework for further investigation of specific
      experimental systems.

PMID- 22482586
TI  - An enhanced entangled polymer model for dissipative particle dynamics.
AB  - We develop an alternative polymer model to capture entanglements within the
      dissipative particle dynamics (DPD) framework by using simplified bond-bond
      repulsive interactions to prevent bond crossings. We show that structural and
      thermodynamic properties can be improved by applying a segmental repulsive
      potential (SRP) that is a function of the distance between the midpoints of the
      segments, rather than the minimum distance between segments. The alternative
      approach, termed the modified segmental repulsive potential (mSRP), is shown to
      produce chain structures and thermodynamic properties that are similar to the
      softly repulsive, flexible chains of standard DPD. Parameters for the mSRP are
      determined from topological, structural, and thermodynamic considerations. The
      effectiveness of the mSRP in capturing entanglements is demonstrated by
      calculating the diffusion and mechanical properties of an entangled polymer melt.

PMID- 22482587
TI  - Prediction of the effects of constitutive viscoelasticity on stress-diffusion
      coupling in gels.
AB  - Modeling of stress/diffusion coupling in gels, originally developed by Doi for
      the case where the solid component of the gel is a linear elastic network, is
      here extended to the case of a linear viscoelastic solid component, thereby
      allowing for a mechanism of intrinsic relaxation. The extended model is solved
      for a cylindrical gel subjected to unconfined uniaxial compression. Depending on
      the respective values of the two characteristic times, i.e., diffusive and
      viscoelastic, measurable quantities like axial force and external radius of the
      cylindrical gel are calculated to display different qualitative behaviors.
      Calculated results for the case of uniaxial traction are also reported, which
      compare favorably with some available experimental results.

PMID- 22482589
TI  - Solvent effect on the folding dynamics and structure of E6-associated protein
      characterized from ab initio protein folding simulations.
AB  - Solvent effect on protein conformation and folding mechanism of E6-associated
      protein (E6ap) peptide are investigated using a recently developed charge update
      scheme termed as adaptive hydrogen bond-specific charge (AHBC). On the basis of
      the close agreement between the calculated helix contents from AHBC simulations
      and experimental results, we observed based on the presented simulations that the
      two ends of the peptide may simultaneously take part in the formation of the
      helical structure at the early stage of folding and finally merge to form a helix
      with lowest backbone RMSD of about 0.9 A in 40% 2,2,2-trifluoroethanol solution.
      However, in pure water, the folding may start at the center of the peptide
      sequence instead of at the two opposite ends. The analysis of the free energy
      landscape indicates that the solvent may determine the folding clusters of E6ap,
      which subsequently leads to the different final folded structure. The current
      study demonstrates new insight to the role of solvent in the determination of
      protein structure and folding dynamics.

PMID- 22482588
TI  - Langevin dynamics simulation of polymer-assisted virus-like assembly.
AB  - Starting from a coarse grained representation of the building units of the minute
      virus of mice and a flexible polyelectrolyte molecule, we have explored the
      mechanism of assembly into icosahedral structures with the help of Langevin
      dynamics simulations and the parallel tempering technique. Regular icosahedra
      with appropriate symmetry form only in a narrow range of temperature and polymer
      length. Within this region of parameters where successful assembly would proceed,
      we have systematically investigated the growth kinetics. The assembly of
      icosahedra is found to follow the classical nucleation and growth mechanism in
      the absence of the polymer, with the three regimes of nucleation, linear growth,
      and slowing down in the later stage. The calculated average nucleation time obeys
      the laws expected from the classical nucleation theory. The linear growth rate is
      found to obey the laws of secondary nucleation as in the case of lamellar growth
      in polymer crystallization. The same mechanism is seen in the simulations of the
      assembly of icosahedra in the presence of the polymer as well. The polymer
      reduces the nucleation barrier significantly by enhancing the local concentration
      of subunits via adsorbing them on their backbone. The details of growth in the
      presence of the polymer are also found to be consistent with the classical
      nucleation theory, despite the smallness of the assembled structures.

PMID- 22482590
TI  - Note: Anharmonicity of quasi-lattice modes in glass and super-fragile liquid
      states of decahydroisoqinoline: C9H17N.

PMID- 22482591
TI  - Note: An exact scaling relation for truncatable free energies of polydisperse
      hard-sphere mixtures.

PMID- 22482593
TI  - Point/counterpoint: we do not need randomized clinical trials to demonstrate the
      superiority of proton therapy.

PMID- 22482594
TI  - Real-time scintillation array dosimetry for radiotherapy: the advantages of
      photomultiplier detectors.
AB  - PURPOSE: In this paper, a photomultiplier tube (PMT) array dosimetry system has
      been developed and tested for the real-time readout of multiple scintillation
      signals from fiber optic dosimeters. It provides array dosimetry with the
      advantages in sensitivity provided by a PMT, but without the need for a separate
      PMT for each detector element. METHODS: The PMT array system consisted of a
      multianode PMT, a multichannel data acquisition system, housing and optic fiber
      connections suitable for clinical use. The reproducibility, channel uniformity,
      channel crosstalk, acquisition speed, and sensitivity of the PMT array were
      quantified using a constant light source. Its performance was compared to other
      readout systems used in scintillation dosimetry. An in vivo HDR brachytherapy
      treatment was used as an example of a clinical application of the dosimetry
      system to the measurement of dose at multiple sites in the rectum. The PMT array
      system was also tested in the pulsed beam of a linear accelerator to test its
      response speed and its application with two separate methods of Cerenkov
      background removal. RESULTS: The PMT array dosimetry system was highly
      reproducible with a measurement uncertainty of 0.13% for a 10 s acquisition
      period. Optical crosstalk between neighboring channels was accounted for by
      omitting every second channel. A mathematical procedure was used to account for
      the crosstalk in next-neighbor channels. The speed and sensitivity of the PMT
      array system were found be superior to CCD cameras, allowing for measurement of
      more rapid changes in dose rate. This was further demonstrated by measuring the
      dose delivered by individual photon pulses of a linear accelerator beam.
      CONCLUSIONS: The PMT array system has advantages over CCD camera-based systems
      for the readout of scintillation light. It provided a more sensitive, more
      accurate, and faster response to meet the demands of future developments in
      treatment delivery.

PMID- 22482595
TI  - Respiratory motion sampling in 4DCT reconstruction for radiotherapy.
AB  - PURPOSE: Phase-based and amplitude-based sorting techniques are commonly used in
      four-dimensional CT (4DCT) reconstruction. However, effect of these sorting
      techniques on 4D dose calculation has not been explored. In this study, the
      authors investigated a candidate 4DCT sorting technique by comparing its 4D dose
      calculation accuracy with that for phase-based and amplitude-based sorting
      techniques. METHOD: An optimization model was formed using organ motion
      probability density function (PDF) in the 4D dose convolution. The objective
      function for optimization was defined as the maximum difference between the
      expected 4D dose in organ of interest and the 4D dose calculated using a 4DCT
      sorted by a candidate sampling method. Sorting samples, as optimization
      variables, were selected on the respiratory motion PDF assessed during the CT
      scanning. Breathing curves obtained from patients' 4DCT scanning, as well as 3D
      dose distribution from treatment planning, were used in the study. Given the
      objective function, a residual error analysis was performed, and k-means
      clustering was found to be an effective sampling scheme to improve the 4D dose
      calculation accuracy and independent with the patient-specific dose distribution.
      RESULTS: Patient data analysis demonstrated that the k-means sampling was
      superior to the conventional phase-based and amplitude-based sorting and
      comparable to the optimal sampling results. For phase-based sorting, the residual
      error in 4D dose calculations may not be further reduced to an acceptable
      accuracy after a certain number of phases, while for amplitude-based sorting, k
      means sampling, and the optimal sampling, the residual error in 4D dose
      calculations decreased rapidly as the number of 4DCT phases increased to 6.
      CONCLUSION: An innovative phase sorting method (k-means method) is presented in
      this study. The method is dependent only on tumor motion PDF. It could provide a
      way to refine the phase sorting in 4DCT reconstruction and is effective for 4D
      dose accumulation. Optimized sorting techniques could achieve acceptable
      residuals (less than 0.5% of the prescription dose) using 6 sorting samples,
      which is much better than amplitude-based or phase-based sorting. Further
      increase in sorting phase number exceeding 6 or more may not be necessary when
      using the k-means sampling or optimal sampling points.

PMID- 22482596
TI  - Computer-aided diagnosis for dynamic contrast-enhanced breast MRI of mass-like
      lesions using a multiparametric model combining a selection of morphological,
      kinetic, and spatiotemporal features.
AB  - PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a
      radiological tool for the detection and discrimination of breast lesions. The aim
      of this study is to evaluate a computer-aided diagnosis (CAD) system for
      discriminating malignant from benign breast lesions at DCE-MRI by the combined
      use of morphological, kinetic, and spatiotemporal lesion features. METHODS: Fifty
      four malignant and 19 benign breast lesions in 51 patients were retrospectively
      evaluated. Images were acquired at two centers at 1.5 T. Mass-like lesions were
      automatically segmented after image normalization and elastic coregistration of
      contrast-enhanced frames. For each lesion, a set of 28 3D features were
      extracted: ten morphological (related to shape, margins, and internal enhancement
      distribution); nine kinetic (computed from signal-to-time curves); and nine
      spatiotemporal (related to the variation of the signal between adjacent frames).
      A support vector machine (SVM) was trained with feature subsets selected by a
      genetic search. Best subsets were composed of the most frequent features selected
      by majority rule. The performance was measured by receiver operator
      characteristics analysis with a stratified tenfold cross-validation and bootstrap
      method for confidence intervals. RESULTS: SVM training by the three separated
      classes of features resulted in an area under the curve (AUC) of 0.90 +/- 0.04
      (mean +/- standard deviation), 0.87 +/- 0.06, and 0.86 +/- 0.06 for
      morphological, kinetic, and spatiotemporal feature, respectively. Combined
      training with all 28 features resulted in AUC of 0.96 +/- 0.02 obtained with a
      selected feature subset composed by two morphological, one kinetic, and two
      spatiotemporal features. CONCLUSIONS: Quantitative combination of morphological,
      kinetic, and spatiotemporal features is feasible and provides a higher
      discriminating power than using the three different classes of features
      separately.

PMID- 22482597
TI  - Particle therapy for noncancer diseases.
AB  - Radiation therapy using high-energy charged particles is generally acknowledged
      as a powerful new technique in cancer treatment. However, particle therapy in
      oncology is still controversial, specifically because it is unclear whether the
      putative clinical advantages justify the high additional costs. However, particle
      therapy can find important applications in the management of noncancer diseases,
      especially in radiosurgery. Extension to other diseases and targets (both cranial
      and extracranial) may widen the applications of the technique and decrease the
      cost/benefit ratio of the accelerator facilities. Future challenges in this field
      include the use of different particles and energies, motion management in
      particle body radiotherapy and extension to new targets currently treated by
      catheter ablation (atrial fibrillation and renal denervation) or stereotactic
      radiation therapy (trigeminal neuralgia, epilepsy, and macular degeneration).
      Particle body radiosurgery could be a future key application of accelerator-based
      particle therapy facilities in 10 years from today.

PMID- 22482598
TI  - Quality assurance for nonradiographic radiotherapy localization and positioning
      systems: report of Task Group 147.
AB  - New technologies continue to be developed to improve the practice of radiation
      therapy. As several of these technologies have been implemented clinically, the
      Therapy Committee and the Quality Assurance and Outcomes Improvement Subcommittee
      of the American Association of Physicists in Medicine commissioned Task Group 147
      to review the current nonradiographic technologies used for localization and
      tracking in radiotherapy. The specific charge of this task group was to make
      recommendations about the use of nonradiographic methods of localization,
      specifically; radiofrequency, infrared, laser, and video based patient
      localization and monitoring systems. The charge of this task group was to review
      the current use of these technologies and to write quality assurance guidelines
      for the use of these technologies in the clinical setting. Recommendations
      include testing of equipment for initial installation as well as ongoing quality
      assurance. As the equipment included in this task group continues to evolve, both
      in the type and sophistication of technology and in level of integration with
      treatment devices, some of the details of how one would conduct such testing will
      also continue to evolve. This task group, therefore, is focused on providing
      recommendations on the use of this equipment rather than on the equipment itself,
      and should be adaptable to each user's situation in helping develop a
      comprehensive quality assurance program.

PMID- 22482599
TI  - A novel breast software phantom for biomechanical modeling of elastography.
AB  - PURPOSE: In developing breast imaging technologies, testing is done with
      phantoms. Physical phantoms are normally used but their size, shape, composition,
      and detail cannot be modified readily. These difficulties can be avoided by
      creating a software breast phantom. Researchers have created software breast
      phantoms using geometric and/or mathematical methods for applications like image
      fusion. The authors report a 3D software breast phantom that was built using a
      mechanical design tool, to investigate the biomechanics of elastography using
      finite element modeling (FEM). The authors propose this phantom as an
      intermediate assessment tool for elastography simulation; for use after testing
      with commonly used phantoms and before clinical testing. The authors design the
      phantom to be flexible in both, the breast geometry and biomechanical parameters,
      to make it a useful tool for elastography simulation. METHODS: The authors
      develop the 3D software phantom using a mechanical design tool based on
      illustrations of normal breast anatomy. The software phantom does not use
      geometric primitives or imaging data. The authors discuss how to create this
      phantom and how to modify it. The authors demonstrate a typical elastography
      experiment of applying a static stress to the top surface of the breast just
      above a simulated tumor and calculate normal strains in 3D and in 2D with plane
      strain approximations with linear solvers. In particular, they investigate
      contrast transfer efficiency (CTE) by designing a parametric study based on
      location, shape, and stiffness of simulated tumors. The authors also compare
      their findings to a commonly used elastography phantom. RESULTS: The 3D breast
      software phantom is flexible in shape, size, and location of tumors, glandular to
      fatty content, and the ductal structure. Residual modulus, maps, and profiles,
      served as a guide to optimize meshing of this geometrically nonlinear phantom for
      biomechanical modeling of elastography. At best, low residues (around 1-5 KPa)
      were found within the phantom while errors were elevated (around 10-30 KPa) at
      tumor and lobule boundaries. From our FEM analysis, the breast phantom generated
      a superior CTE in both 2D and in 3D over the block phantom. It also showed
      differences in CTE values and strain contrast for deep and shallow tumors and
      showed significant change in CTE when 3D modeling was used. These changes were
      not significant in the block phantom. Both phantoms, however, showed worsened CTE
      values for increased input tumor-background modulus contrast. CONCLUSIONS: Block
      phantoms serve as a starting tool but a next level phantom, like the proposed
      breast phantom, will serve as a valuable intermediate for elastography simulation
      before clinical testing. Further, given the CTE metrics for the breast phantom
      are superior to the block phantom, and vary for tumor shape, location, and
      stiffness, these phantoms would enhance the study of elastography contrast.
      Further, the use of 2D phantoms with plane strain approximations overestimates
      the CTE value when compared to the true CTE achieved with 3D models. Thus, the
      use of 3D phantoms, like the breast phantom, with no approximations, will assist
      in more accurate estimation of modulus, especially valuable for 3D elastography
      systems.

PMID- 22482600
TI  - Robust calculation of effective atomic numbers: the Auto-Z(eff) software.
AB  - PURPOSE: The most appropriate method of evaluating the effective atomic number
      necessitates consideration of energy-dependent behavior. Previously, this
      required quite laborious calculation, which is why many scientists revert to over
      simplistic power-law methods. The purpose of this work is to develop user
      friendly software for the robust, energy-dependent computation of effective
      atomic numbers relevant within the context of medical physics, superseding the
      commonly employed simplistic power law approaches. METHOD: Visual Basic was used
      to develop a GUI allowing the straightforward calculation of effective atomic
      numbers. Photon interaction cross section matrices are constructed for energies
      spanning 10 keV to 10 GeV and elements Z = 1-100. Coefficients for composite
      media are constructed via linear additivity of the fractional constituents and
      contrasted against the precalculated matrices at each energy, thereby associating
      an effective atomic number through interpolation of adjacent cross section data.
      Uncertainties are of the order of 1-2%. RESULTS: Auto-Z(eff) allows rapid (~0.6
      s) calculation of effective atomic numbers for a range of predefined or user
      specified media, allowing estimation of radiological properties and comparison of
      different media (for instance assessment of water equivalence). The accuracy of
      Auto-Z(eff) has been validated against numerous published theoretical and
      experimental predictions, demonstrating good agreement. The results also show
      that commonly employed power-law approaches are inaccurate, even in their
      intended regime of applicability (i.e., photoelectric regime). Furthermore,
      comparing the effective atomic numbers of composite materials using power-law
      approaches even in a relative fashion is shown to be inappropriate. CONCLUSION:
      Auto-Z(eff) facilitates easy computation of effective atomic numbers as a
      function of energy, as well as average and spectral-weighted means. The results
      are significantly more accurate than normal power-law predictions. The software
      is freely available to interested readers, who are encouraged to contact the
      authors.

PMID- 22482601
TI  - Lagrangian displacement tracking using a polar grid between endocardial and
      epicardial contours for cardiac strain imaging.
AB  - PURPOSE: Accurate cardiac deformation analysis for cardiac displacement and
      strain imaging over time requires Lagrangian description of deformation of
      myocardial tissue structures. Failure to couple the estimated displacement and
      strain information with the correct myocardial tissue structures will lead to
      erroneous result in the displacement and strain distribution over time. METHODS:
      Lagrangian based tracking in this paper divides the tissue structure into a fixed
      number of pixels whose deformation is tracked over the cardiac cycle. An
      algorithm that utilizes a polar-grid generated between the estimated endocardial
      and epicardial contours for cardiac short axis images is proposed to ensure
      Lagrangian description of the pixels. Displacement estimates from consecutive
      radiofrequency frames were then mapped onto the polar grid to obtain a
      distribution of the actual displacement that is mapped to the polar grid over
      time. RESULTS: A finite element based canine heart model coupled with an
      ultrasound simulation program was used to verify this approach. Segmental
      analysis of the accumulated displacement and strain over a cardiac cycle
      demonstrate excellent agreement between the ideal result obtained directly from
      the finite element model and our Lagrangian approach to strain estimation.
      Traditional Eulerian based estimation results, on the other hand, show
      significant deviation from the ideal result. An in vivo comparison of the
      displacement and strain estimated using parasternal short axis views is also
      presented. CONCLUSIONS: Lagrangian displacement tracking using a polar grid
      provides accurate tracking of myocardial deformation demonstrated using both
      finite element and in vivo radiofrequency data acquired on a volunteer. In
      addition to the cardiac application, this approach can also be utilized for
      transverse scans of arteries, where a polar grid can be generated between the
      contours delineating the outer and inner wall of the vessels from the blood
      flowing though the vessel.

PMID- 22482602
TI  - Validation of continuously tagged MRI for the measurement of dynamic 3D skeletal
      muscle tissue deformation.
AB  - PURPOSE: Typically spatial modulation of the magnetization (SPAMM) tagged
      magnetic resonance imaging (MRI) requires many repeated motion cycles limiting
      the applicability to highly repeatable tissue motions only. This paper describes
      the validation of a novel SPAMM tagged MRI and post-processing framework for the
      measurement of complex and dynamic 3D soft tissue deformation following just
      three motion cycles. Techniques are applied to indentation induced deformation
      measurement of the upper arm and a silicone gel phantom. METHODS: A SPAMM tagged
      MRI methodology is presented allowing continuous (3.3-3.6 Hz) sampling of 3D
      dynamic soft tissue deformation using non segmented 3D acquisitions. The 3D
      deformation is reconstructed by the combination of three mutually orthogonal
      tagging directions, thus requiring only three repeated motion cycles. In addition
      a fully automatic post-processing framework is presented employing Gabor scale
      space and filter-bank analysis for tag extrema segmentation and triangulated
      surface fitting aided by Gabor filter bank derived surface normals. Deformation
      is derived following tracking of tag surface triplet triangle intersections. The
      dynamic deformation measurements were validated using indentation tests (~20 mm
      deep at 12 mm/s) on a silicone gel soft tissue phantom containing contrasting
      markers which provide a reference measure of deformation. In addition, the
      techniques were evaluated in vivo for dynamic skeletal muscle tissue deformation
      measurement during indentation of the biceps region of the upper arm in a
      volunteer. RESULTS: For the phantom and volunteer tag point location precision
      were 44 and 92 MUm, respectively resulting in individual displacements precisions
      of 61 and 91 MUm, respectively. For both the phantom and volunteer data
      cumulative displacement measurement accuracy could be evaluated and the
      difference between initial and final locations showed a mean and standard
      deviation of 0.44 and 0.59 mm for the phantom and 0.40 and 0.73 mm for the human
      data. Finally accuracy of (cumulative) displacement was evaluated using marker
      tracking in the silicone gel phantom. Differences between true and predicted
      marker locations showed a mean of 0.35 mm and a standard deviation of 0.63 mm.
      CONCLUSIONS: A novel SPAMM tagged MRI and fully automatic post-processing
      framework for the measurement of complex 3D dynamic soft tissue deformation
      following just three repeated motion cycles was presented. The techniques
      demonstrate dynamic measurement of complex 3D soft tissue deformation at subvoxel
      accuracy and precision and were validated for 3.3-3.6 Hz sampling of deformation
      speeds up to 12 mm/s.

PMID- 22482603
TI  - Effects of insertion speed and trocar stiffness on the accuracy of needle
      position for brachytherapy.
AB  - PURPOSE: In prostate brachytherapy, accurate positioning of the needle tip to
      place radioactive seeds at its target site is critical for successful radiation
      treatment. During the procedure, needle deflection leads to seed misplacement and
      suboptimal radiation dose to cancerous cells. In practice, radiation oncologists
      commonly use high-speed hand needle insertion to minimize displacement of the
      prostate as well as the needle deflection. Effects of speed during needle
      insertion and stiffness of trocar (a solid rod inside the hollow cannula) on
      needle deflection are studied. METHODS: Needle insertion experiments into phantom
      were performed using a 2(2) factorial design (2 parameters at 2 levels), with
      each condition having replicates. Analysis of the deflection data included
      calculating the average, standard deviation, and analysis of variance (ANOVA) to
      find significant single and two-way interaction factors. RESULTS: The stiffer
      tungsten carbide trocar is effective in reducing the average and standard
      deviation of needle deflection. The fast insertion speed together with the
      stiffer trocar generated the smallest average and standard deviation for needle
      deflection for almost all cases. CONCLUSIONS: The combination of stiff tungsten
      carbide trocar and fast needle insertion speed are important to decreasing needle
      deflection. The knowledge gained from this study can be used to improve the
      accuracy of needle insertion during brachytherapy procedures.

PMID- 22482604
TI  - Effect of slice thickness on detectability in breast CT using a prewhitened
      matched filter and simulated mass lesions.
AB  - PURPOSE: Dedicated breast CT (bCT) is an emerging technology with the potential
      to improve the detection of breast cancer in screening and diagnostic capacities.
      Typically, the 3D volume reconstructed from the scanner is displayed as sectional
      images. The purpose of this study was to evaluate the effect of section thickness
      on the detectability of simulated masses using a prewhitened matched filter
      (PWMF) as a model observer. METHODS: A breast CT scanner has been designed and
      fabricated in the authors' laboratory with more than 200 women imaged in IRB
      approved phase I and phase II trials to date. Of these, 151 bilateral data sets
      were selected on the basis of low artifact content, sufficient breast coverage,
      and excluding cases with breast implants. BIRADS breast density ratings were
      available for 144 of these patients. Spherical mass lesions of diameter 1, 2, 3,
      5, 11, and 15 mm were mathematically generated and embedded at random locations
      within the parenchymal region of each bCT volume. Microcalcifications were not
      simulated in this study. For each viewing plane (sagittal, axial, and coronal)
      and section thickness (ranging from 0.3 to 44 mm), section images of the breast
      parenchyma containing the lesion were generated from the reconstructed bCT data
      sets by averaging voxels over the length of the section. Using signal known
      exactly (SKE) model observer methodology, receiver operating characteristic (ROC)
      curve analysis was performed on each generated projected image using a PWMF based
      model observer. ROC curves were generated for each breast data set, and the area
      under the ROC curve (AUC) was evaluated as well as the sensitivity at 95%
      specificity. RESULTS: For all lesion sizes, performance rises modestly to a peak
      before falling off substantially as section thickness increases over the range of
      the study. We find that the optimal section thickness tracks the size of the
      lesion to be detected linearly with a small positive offset and slopes ranging
      from 0.27 to 0.44. No significant differences were observed between left and
      right breasts. Performance measures are negatively correlated with measures of
      breast density, with an average correlation coefficient of -0.48 for the BIRADS
      breast density score and -0.81 for the proportion of glandular tissue in the
      breast interior. CONCLUSIONS: This study shows quantitatively how PWMF detection
      performance of a known lesion size is influenced by section thickness in
      dedicated breast CT. While the optimal section thickness is tuned to the size of
      the lesion being detected, overall performance is more robust for thin section
      images compared to thicker images.

PMID- 22482605
TI  - How to improve x-ray scattering techniques to quantify bone mineral density using
      spectroscopy.
AB  - PURPOSE: The purpose of this study was to develop a new diagnostic technique for
      measuring bone mineral density (BMD) for the assessment of osteoporosis, which
      improves upon the coherent to Compton scattering ratio (CCSR) method, which was
      first developed in the 1980s. To help the authors achieve these goals, they have
      identified and studied two new indices for CCSR, the forward scattered to
      backward scattered (FS-BS) and the forward scattered to transmitted (FS-T)
      ratios. They believe that, at small angles, these two parameters can offer a
      practical in vivo determination of BMD that can be used to overcome the
      limitations of past CCSR systems, including high radiation dosages, costs, and
      examination durations. METHODS: In previous CCSR studies, a high-activity
      radioactive source with a long half-live (usually (241)Am) and an expensive and
      bulky cryogenic HPGe detector were applied to both in vivo and in vitro
      measurements. To make this technique more suitable for clinical applications, the
      possibility of using a standard diagnostic x-ray tube generating a continuous
      spectrum was investigated in this paper. Scattered radiation from trabecular bone
      simulating phantoms containing various mineral densities that span the normal
      range of in vivo BMD was collected in this study using relatively inexpensive
      noncryogenic CdTe or NaI detectors. RESULTS: The initial results demonstrate that
      a modified version of CCSR can be successfully applied to trabecular bone
      assessment using a diagnostic x-ray tube with a continuous spectrum in two
      variations, the FS-BS and the FS-T ratio. When FS-BS is measured, intensity
      spectra in the forward and backward directions must be collected while FS-T
      requires only the integral intensity of the scattered and transmitted (T) spectra
      in the energy region above 40 keV. For both of these methods, forward scattering
      angles less than or equal to 15 degrees  and backward scattering angles greater
      than or equal to (165 degrees = 180 degrees  - 15 degrees ) are needed.
      CONCLUSIONS: The authors determined that FS-T is more sensitive to changes in BMD
      than transmission or absorption alone and that the FS-BS method can yield an
      absolute measurement of the mean atomic number of the scattering medium, after a
      correction for path-dependent attenuation. Since this study determined that the
      FS-T ratio is independent of the incident energy over a broad energy region, it
      will be possible to apply FS-T to bone densitometry using inexpensive integral
      photon detectors. The authors believe that, by replacing the radionuclide source
      with an x-ray tube and the cryogenically cooled HPGe detector with a single solid
      state CdTe, NaI, or silicon detector or an annular array of detectors, as
      suggested in this study, the past difficulties of CCSR concerning high radiation
      exposure, costs, and durations as well as lack of convenience can be overcome and
      that CCSR could eventually become popular in clinical settings.

PMID- 22482606
TI  - RapidArc patient specific mechanical delivery accuracy under extreme mechanical
      limits using linac log files.
AB  - PURPOSE: To assess the accuracy of RapidArc (RA) delivery for treatment machine
      operation near allowable mechanical limits in dynamic multileaf collimator (DMLC)
      leaf velocities, gantry speeds, and dose rates. METHODS: Thirty RA patient plans
      were created for treatment of lung, gastrointestinal, and head and neck cancers
      on a Trilogy unit. For each patient, three RA plans were generated; one with
      medium MLC velocities, highest gantry speeds, and dose rates (case A); one with
      maximal allowable MLC leaf velocities (case B); and one with lowest gantry speeds
      (case C). Combinations of dose rates (140-600 MU/min), gantry speeds (2-5.4
      degrees /s), and DMLC leaf velocities (1.3-2.4 cm/s) were utilized to test the
      RapidArc delivery accuracy. Linac delivery log files were acquired after delivery
      of each plan. In-house developed software was used to read in the original
      RapidArc DICOM plan and update the plan to reflect the delivered plan by using
      the leaf position (L), gantry position (G), and MU dose values (D) extracted from
      the linac log files. This modified DICOM RT plan was imported back to ECLIPSE and
      the delivered 3D dose map recomputed. Finally, the planned and delivered 3D
      isodose maps were compared under three criteria to evaluate the dosimetric
      differences: maximum percentage dose difference, 3D gamma analysis criteria for
      3%/3mm DTA, number of dose voxels having a dose difference that is greater than
      1%, 2%, or 3% of the maximum dose, and their respective percentages. RESULTS: For
      the three cases indicated above, MLC leaf position discrepancies between planned
      and delivered values are 0.8 +/- 0.2, 1.2 +/- 0.2, and 0.8 +/- 0.2 mm; the
      maximum gantry position discrepancies are 0.9 degrees  +/- 0.2 degrees , 0.9
      degrees  +/- 0.2 degrees , and 0.6 degrees  +/- 0.1 degrees , and the maximum
      differences in delivered MU per control point are 0.2 +/- 0.1, 0.2 +/- 0.1, and
      0.04 +/- 0.01, respectively. Maximum percentage dose difference observed is 6.7%,
      for a case where 1 cm MLC leaves were used with high MLC leaf velocity. Maximum
      number (percentage) of dose voxels having a dose difference that is greater than
      1%, 2%, and 3% of the maximum dose were 4761 (0.35%), 897 (0.07%), and 188
      (0.01%). This also corresponds to the plan utilizing the most number of 1 cm MLC
      leaves. The 3D Gamma factor acceptance rates are better than 99%. CONCLUSIONS:
      This work shows that the accuracy of RapidArc delivery holds across the full
      range of gantry speeds, leaf velocities, and dose rates with small dosimetric
      uncertainties for 0.5 cm MLC leaves. However, caution should be exercised when
      using large MLC leaves in RapidArc. A novel technique to obtain the delivered 3D
      dose distributions using machine log files is also presented.

PMID- 22482607
TI  - Characteristics of optically stimulated luminescence dosimeters in the spread-out
      Bragg peak region of clinical proton beams.
AB  - PURPOSE: Optically stimulated luminescent detectors (OSLDs) have a number of
      advantages in radiation dosimetry making them excellent dosimeters for quality
      assurance and patient dose verification. Although the dosimeters have been
      investigated in several modalities, relatively little work has been done in
      examining the dosimeters for use in clinical proton beams. This study examined a
      number of characteristics of the response of the dosimeters in the spread-out
      Bragg peak (SOBP) region of clinical proton beams. METHODS: Optically stimulated
      luminescence (OSL) dosimeters from Landauer, Inc., specifically the nanoDot
      dosimeter, were investigated. These dosimeters were placed in a special phantom
      with a recess to fit the dosimeters without an air gap. Beams with nominal
      energies of 160, 200, and 250 MeV were used in the passively-scattered proton
      beam at the MD Anderson Cancer Center Proton Therapy Center. Dosimetric
      properties including linearity, field size dependence, energy dependence,
      residual signal as a function of cumulative dose, and postirradiation fading were
      investigated by taking measurements at the center of SOBPs. RESULTS: The
      dosimeters showed 1% supralinearity at 200 cGy and 5% supralinearity at 1000 cGy.
      No noticeable field size dependence of the detector was found for field sizes
      from 2 * 2 cm(2) to 18 * 18 cm(2). Residual signal as a function of cumulative
      dose showed a small increase for measurements up to 1000 cGy. Readout signal
      depletion of the dosimeters after consecutive readings showed a slightly larger
      depletion in protons for doses up to 500 cGy but not by a clinically significant
      amount. Within the center of various SOBP widths and proton energies the
      variation in response was less than 2%. An average beam quality factor of 1.089
      with experimental standard deviation of 0.007 was determined and applied to the
      data such that the results were within 1.2% of ion chamber data. CONCLUSIONS: The
      nanoDot OSL dosimeter characteristics were studied in the SOBP region of clinical
      proton beams. To achieve accurate dosimetric readings, corrections to the
      dosimeter response were applied. Corrections tended to be minimal or broadly
      consistent. The nanoDot OSLD was found to be an acceptable dosimeter for
      measurement in the SOBP region for a range of clinical proton beams.

PMID- 22482608
TI  - Image-based spectral distortion correction for photon-counting x-ray detectors.
AB  - PURPOSE: To investigate the feasibility of using an image-based method to correct
      for distortions induced by various artifacts in the x-ray spectrum recorded with
      photon-counting detectors for their application in breast computed tomography
      (CT). METHODS: The polyenergetic incident spectrum was simulated with the
      tungsten anode spectral model using the interpolating polynomials (TASMIP) code
      and carefully calibrated to match the x-ray tube in this study. Experiments were
      performed on a Cadmium-Zinc-Telluride (CZT) photon-counting detector with five
      energy thresholds. Energy bins were adjusted to evenly distribute the recorded
      counts above the noise floor. BR12 phantoms of various thicknesses were used for
      calibration. A nonlinear function was selected to fit the count correlation
      between the simulated and the measured spectra in the calibration process. To
      evaluate the proposed spectral distortion correction method, an empirical fitting
      derived from the calibration process was applied on the raw images recorded for
      polymethyl methacrylate (PMMA) phantoms of 8.7, 48.8, and 100.0 mm. Both the
      corrected counts and the effective attenuation coefficient were compared to the
      simulated values for each of the five energy bins. The feasibility of applying
      the proposed method to quantitative material decomposition was tested using a
      dual-energy imaging technique with a three-material phantom that consisted of
      water, lipid, and protein. The performance of the spectral distortion correction
      method was quantified using the relative root-mean-square (RMS) error with
      respect to the expected values from simulations or areal analysis of the
      decomposition phantom. RESULTS: The implementation of the proposed method reduced
      the relative RMS error of the output counts in the five energy bins with respect
      to the simulated incident counts from 23.0%, 33.0%, and 54.0% to 1.2%, 1.8%, and
      7.7% for 8.7, 48.8, and 100.0 mm PMMA phantoms, respectively. The accuracy of the
      effective attenuation coefficient of PMMA estimate was also improved with the
      proposed spectral distortion correction. Finally, the relative RMS error of
      water, lipid, and protein decompositions in dual-energy imaging was significantly
      reduced from 53.4% to 6.8% after correction was applied. CONCLUSIONS: The study
      demonstrated that dramatic distortions in the recorded raw image yielded from a
      photon-counting detector could be expected, which presents great challenges for
      applying the quantitative material decomposition method in spectral CT. The
      proposed semi-empirical correction method can effectively reduce these errors
      caused by various artifacts, including pulse pileup and charge sharing effects.
      Furthermore, rather than detector-specific simulation packages, the method
      requires a relatively simple calibration process and knowledge about the incident
      spectrum. Therefore, it may be used as a generalized procedure for the spectral
      distortion correction of different photon-counting detectors in clinical breast
      CT systems.

PMID- 22482609
TI  - Validation of GPU based TomoTherapy dose calculation engine.
AB  - PURPOSE: The graphic processing unit (GPU) based TomoTherapy
      convolution/superposition(C/S) dose engine (GPU dose engine) achieves a dramatic
      performance improvement over the traditional CPU-cluster based TomoTherapy dose
      engine (CPU dose engine). Besides the architecture difference between the GPU and
      CPU, there are several algorithm changes from the CPU dose engine to the GPU dose
      engine. These changes made the GPU dose slightly different from the CPU-cluster
      dose. In order for the commercial release of the GPU dose engine, its accuracy
      has to be validated. METHODS: Thirty eight TomoTherapy phantom plans and 19
      patient plans were calculated with both dose engines to evaluate the equivalency
      between the two dose engines. Gamma indices (Gamma) were used for the equivalency
      evaluation. The GPU dose was further verified with the absolute point dose
      measurement with ion chamber and film measurements for phantom plans. Monte Carlo
      calculation was used as a reference for both dose engines in the accuracy
      evaluation in heterogeneous phantom and actual patients. RESULTS: The GPU dose
      engine showed excellent agreement with the current CPU dose engine. The majority
      of cases had over 99.99% of voxels with Gamma(1%, 1 mm) < 1. The worst case
      observed in the phantom had 0.22% voxels violating the criterion. In patient
      cases, the worst percentage of voxels violating the criterion was 0.57%. For
      absolute point dose verification, all cases agreed with measurement to within +/
      3% with average error magnitude within 1%. All cases passed the acceptance
      criterion that more than 95% of the pixels have Gamma(3%, 3 mm) < 1 in film
      measurement, and the average passing pixel percentage is 98.5%-99%. The GPU dose
      engine also showed similar degree of accuracy in heterogeneous media as the
      current TomoTherapy dose engine. CONCLUSIONS: It is verified and validated that
      the ultrafast TomoTherapy GPU dose engine can safely replace the existing
      TomoTherapy cluster based dose engine without degradation in dose accuracy.

PMID- 22482610
TI  - A novel curvilinear approach for prostate seed implantation.
AB  - PURPOSE: A new technique called "curvilinear approach" for prostate seed
      implantation has been proposed. The purpose of this study is to evaluate the
      dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR)
      prostate brachytherapy. METHODS: Twenty LDR prostate brachytherapy cases planned
      intraoperatively with VariSeed planning system and I-125 seeds were randomly
      selected as reference rectilinear cases. All the cases were replanned by using
      curved-needle approach keeping the same individual source strength and the volume
      receiving 100% of prescribed dose 145 Gy (V(100)). Parameters such as number of
      needles, seeds, and the dose coverage of the prostate (D(90), V(150), V(200)),
      urethra (D(30), D(10)) and rectum (D(5), V(100)) were compared for the
      rectilinear and the curvilinear methods. Statistical significance was assessed
      using two-tailed student's t-test. RESULTS: Reduction of the required number of
      needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p <
      0.49), respectively. Dose to the urethra was reduced significantly; D(30) reduced
      by 10.1% (p < 0.01) and D(10) reduced by 9.9% (p < 0.02). Reduction in rectum
      dose D(5) was 18.5% (p < 0.03) and V(100) was also reduced from 0.93 cc in
      rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V(150) and V(200)
      coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001),
      respectively. CONCLUSIONS: Significant improvement in the relevant dosimetric
      parameters was observed in curvilinear needle approach. Prostate dose homogeneity
      (V(150), V(200)) improved while urethral dose was reduced, which might
      potentially result in better treatment outcome. Reduction in rectal dose could
      potentially reduce rectal toxicity and complications. Reduction in number of
      needles would minimize edema and thereby could improve postimplant urinary
      incontinence. This study indicates that the curvilinear implantation approach is
      dosimetrically superior to conventional rectilinear implantation technique.

PMID- 22482611
TI  - The effect of voxel size on high-resolution peripheral computed tomography
      measurements of trabecular and cortical bone microstructure.
AB  - PURPOSE: Accurate quantification of bone microstructure plays a significant role
      in understanding bone mechanics and response to disease or treatment. High
      resolution peripheral quantitative computed tomography (HR-pQCT) allows for the
      quantification of trabecular and cortical structure in vivo, with the capability
      of generating images at multiple voxel sizes (41, 82, and 123 MUm). The aim of
      this study was to characterize the effect of voxel size on structural measures of
      trabecular and cortical bone and to determine accuracy in reference to micro-CT
      ([micro sign]CT), the gold standard for bone microstructure quantification.
      METHODS: Seventeen radii from human cadaver specimens were imaged at each HR-pQCT
      voxel size and subsequently imaged using [micro sign]CT. Bone density and
      microstructural assessment was performed in both the trabecular and cortical
      compartments, including cortical porosity quantification. Two distinct analysis
      techniques were applied to the 41 MUm HR-pQCT data: the standard clinical
      indirect analysis and a direct analysis requiring no density or structural model
      assumptions. Analysis parameters were adjusted to enable segmentation and
      structure extraction at each voxel size. RESULTS: For trabecular microstructural
      measures, the 41 MUm HR-pQCT data displayed the strongest correlations and
      smallest errors compared to [micro sign]CT data. The direct analysis technique
      applied to the 41 MUm data yielded an additional improvement in accuracy,
      especially for measures of trabecular thickness. The 123 MUm data performed
      poorly, with all microstructural measures either having moderate or
      nonsignificant correlations with [micro sign]CT data. Trabecular densitometric
      measures showed strong correlations to [micro sign]CT data across all voxel
      sizes. Cortical thickness was strongly correlated with [micro sign]CT values
      across all HR-pQCT voxel sizes. The accuracy of cortical porosity parameters was
      highly dependent on voxel size; again, the 41 MUm data was most strongly
      correlated. Measures of cortical density and pore diameter at all HR-pQCT voxel
      sizes had either weak or nonsignificant correlations. CONCLUSIONS: This study
      demonstrates the effect of voxel size on the accuracy of HR-pQCT measurements of
      trabecular and cortical microstructure and presents parameters for HR-pQCT
      analysis at nonstandard resolutions. For all parameters measured, correlations
      were strongest at 41 MUm. Weak correlations for porosity measures indicate that a
      better understanding of pore structure and resolution dependence is needed.

PMID- 22482612
TI  - Frequency split metal artifact reduction (FSMAR) in computed tomography.
AB  - PURPOSE: The problem of metal artifact reduction (MAR) is almost as old as the
      clinical use of computed tomography itself. When metal implants are present in
      the field of measurement, severe artifacts degrade the image quality and the
      diagnostic value of CT images. Up to now, no generally accepted solution to this
      issue has been found. In this work, a method based on a new MAR concept is
      presented: frequency split metal artifact reduction (FSMAR). It ensures efficient
      reduction of metal artifacts at high image quality with enhanced preservation of
      details close to metal implants. METHODS: FSMAR combines a raw data inpainting
      based MAR method with an image-based frequency split approach. Many typical
      methods for metal artifact reduction are inpainting-based MAR methods and simply
      replace unreliable parts of the projection data, for example, by linear
      interpolation. Frequency split approaches were used in CT, for example, by
      combining two reconstruction methods in order to reduce cone-beam artifacts.
      FSMAR combines the high frequencies of an uncorrected image, where all available
      data were used for the reconstruction with the more reliable low frequencies of
      an image which was corrected with an inpainting-based MAR method. The algorithm
      is tested in combination with normalized metal artifact reduction (NMAR) and with
      a standard inpainting-based MAR approach. NMAR is a more sophisticated inpainting
      based MAR method, which introduces less new artifacts which may result from
      interpolation errors. A quantitative evaluation was performed using the examples
      of a simulation of the XCAT phantom and a scan of a spine phantom. Further
      evaluation includes patients with different types of metal implants: hip
      prostheses, dental fillings, neurocoil, and spine fixation, which were scanned
      with a modern clinical dual source CT scanner. RESULTS: FSMAR ensures sharp edges
      and a preservation of anatomical details which is in many cases better than after
      applying an inpainting-based MAR method only. In contrast to other MAR methods,
      FSMAR yields images without the usual blurring close to implants. CONCLUSIONS:
      FSMAR should be used together with NMAR, a combination which ensures an accurate
      correction of both high and low frequencies. The algorithm is computationally
      inexpensive compared to iterative methods and methods with complex inpainting
      schemes. No parameters were chosen manually; it is ready for an application in
      clinical routine.

PMID- 22482613
TI  - Biological consequences of MLC calibration errors in IMRT delivery and QA.
AB  - PURPOSE: The purpose of this work is threefold: (1) to explore biological
      consequences of the multileaf collimator (MLC) calibration errors in intensity
      modulated radiotherapy (IMRT) of prostate and head and neck cancers, (2) to
      determine levels of planning target volume (PTV) and normal tissue under- or
      overdose flagged with clinically used QA action limits, and (3) to provide
      biologically based input for MLC QA and IMRT QA action limits. METHODS: Ten
      consecutive prostate IMRT cases and ten consecutive head and neck IMRT cases were
      used. Systematic MLC offsets (i.e., calibration error) were introduced for each
      control point of the plan separately for X1 and X2 leaf banks. Offsets were from 
      2 to 2 mm with a 0.5 mm increment. The modified files were imported into the
      planning system for forward dose recalculation. The original plan served as the
      reference. The generalized equivalent uniform dose (gEUD) was used as the
      biological index for the targets, rectum, parotid glands, brainstem, and spinal
      cord. Each plan was recalculated on a CT scan of a 27 cm diameter cylindrical
      phantom with a contoured 0.6 cc ion chamber. Dose to ion chamber and 3D gamma
      analysis were compared to the reference plan. QA pass criteria: (1) at least 95%
      of voxels with a dose cutoff of 50% of maximum dose have to pass at 3 mm/3% and
      (2) dose to chamber within 2% of the reference dose. RESULTS: For prostate cases,
      differences in PTV and rectum gEUD greater than 2% were identified. However, a
      larger proportion of plans leading to greater than 2% difference in prostate PTV
      gEUD passed the ion chamber QA but not 3D gamma QA. A similar trend was found for
      the rectum gEUD. For head and neck IMRT, the QA pass criteria flagged plans
      leading to greater than 4% differences in PTV gEUD and greater than 5%
      differences in the maximum dose to brainstem. If pass criteria were relaxed to
      90% for gamma and 3% for ion chamber QA, plans leading to a 5% difference in PTV
      gEUD and a 5%-8% difference in brainstem maximum dose would likely pass IMRT QA.
      A larger proportion of head and neck plans with greater than 2% PTV gEUD
      difference passed 3D gamma QA compared to ion chamber QA. CONCLUSIONS: For low
      modulation plans, there is a better chance to catch MLC calibration errors with
      3D gamma QA rather than ion chamber QA. Conversely, for high modulation plans,
      there is a better chance to catch MLC calibration errors with ion chamber QA
      rather than with 3D gamma QA. Ion chamber and 3D gamma analysis IMRT QA can
      detect greater than 2% change in gEUD for PTVs and critical structures for low
      modulation treatment plans. For high modulation treatment plans, ion chamber and
      3D gamma analysis can detect greater than 2% change in gEUD for PTVs and a 5%
      change in critical structure gEUD since either QA methods passes the QA criteria.
      For gEUD changes less than those listed above, either QA method has the same
      proportion of passing rate.

PMID- 22482614
TI  - In vivo dosimetry for gynaecological brachytherapy using a novel position
      sensitive radiation detector: feasibility study.
AB  - PURPOSE: In gynecological radiotherapy with high dose rate (HDR)(192)Ir
      brachytherapy, the treatment complexity has increased due to improved
      optimization techniques and dose constraints. As a consequence, it has become
      more important to verify the dose delivery to the target and also to the organs
      at risk (e.g., the bladder). In vivo dosimetry, where dosimeters are placed in or
      on the patient, is one way of verifying the dose but until recently this was
      hampered by motion of the radiation detectors with respect to the source. The
      authors present a novel dosimetry method using a position sensitive radiation
      detector. METHODS: The prototype RADPOS system (Best Medical Canada) consists of
      a metal oxide field effect transistor (MOSFET) dosimeter coupled to a position
      sensor, which deduces its 3D position in a magnetic field. To assess the
      feasibility of in vivo dosimetry based on the RADPOS system, different
      characteristics of the detector need to be investigated. Using a PMMA phantom,
      the positioning accuracy of the RADPOS system was quantified by comparing
      position readouts with the known position of the detector along the x and y-axes.
      RADPOS dose measurements were performed at various distances from a
      Nucletron(192)Ir source in a PMMA phantom to evaluate the energy dependence of
      the MOSFET. A sensitivity analysis was performed by calculating the dose after
      varying (1) the position of the RADPOS detector to simulate organ motion and (2)
      the position of the first dwell position to simulate errors in delivery. The
      authors also performed an uncertainty analysis to determine the action level (AL)
      that should be used during in vivo dosimetry. RESULTS: Positioning accuracy is
      found to be within 1 mm in the 1-10 cm range from the origin along the x-axis
      (away from the transmitter), meeting the requirements for in vivo dosimetry.
      Similar results are obtained for the other axes. The ALs are chosen to take into
      account the total uncertainty on the measurements. As a consequence for in vivo
      dosimetry, it is determined that the RADPOS sensor, if placed, for example, in
      the bladder Foley balloon, would detect a 2 mm motion of the bladder, at a 5%
      chance of a false positive, with an AL limit of 9% of the dose delivered. The
      authors found that source position errors, caused by, e.g., a wrong first dwell
      position, are more difficult to detect; indeed, with our single RADPOS detector,
      positioned in the bladder, dwell position errors below 5 mm and resulting in a
      dose error within 10%, could be detected in the tandem but not in the colpostats.
      A possible solution to improve error detection is to use multiple MOSFETs to
      obtain multiple dose values. CONCLUSIONS: In this study, the authors proposed a
      dosimetry procedure, based on the novel RADPOS system, to accurately determine
      the position of the radiation dosimeter with respect to the applicator. The
      authors found that it is possible to monitor the delivered dose in a point and
      compare it to the predetermined dose. This allows in principle the detection of
      problems such as bladder motion/filling or source mispositioning. Further
      clinical investigation is warranted.

PMID- 22482615
TI  - High intensity focused ultrasound with large aperture transducers: a MRI based
      focal point correction for tissue heterogeneity.
AB  - PURPOSE: The risk of undesired tissue damage to thoracic cage, heart, and lung
      during MR guided HIFU ablations of breast cancer can be greatly reduced if a
      phased array transducer design with a lateral beam direction is used in
      combination with a large aperture. The disadvantage is an increased sensitivity
      to focus aberrations due to tissue heterogeneity. Here, the authors propose to
      restore the focal coherence by using a matched aperture phase correction, which
      is based on a noninvasively obtained tissue model. METHODS: The method combines
      high resolution MRI with ultrasound wave measurements of different tissue types
      to determine a phase correction, which compensates focal point aberrations caused
      by tissue heterogeneity. 3D segmentation of tissue is used to quantify the
      relative proportion of each tissue type along a line running from the center of
      each element of the phased array to the target focal point. RESULTS: For tissue
      types with a celerity difference of 3%, the proposed method allows to quantify
      the phase aberration with an accuracy of 6 degrees  +/- 20 degrees  and a
      correlation factor R(2) = 0.95. Using the refocusing method for a complex
      heterogeneous phantom resulted in 95% of the maximal pressure, whereas only 70%
      of the maximal pressure is obtained in absence of any phase correction.
      CONCLUSIONS: Since the proposed refocusing algorithm is compatible with a
      standard interventional preplanning and requires only a minimal amount of
      processing, it presents a promising approach to compensate for aberration in
      heterogeneous tissues such as the human breast.

PMID- 22482616
TI  - Quality assurance for image-guided radiation therapy utilizing CT-based
      technologies: a report of the AAPM TG-179.
AB  - PURPOSE: Commercial CT-based image-guided radiotherapy (IGRT) systems allow
      widespread management of geometric variations in patient setup and internal organ
      motion. This document provides consensus recommendations for quality assurance
      protocols that ensure patient safety and patient treatment fidelity for such
      systems. METHODS: The AAPM TG-179 reviews clinical implementation and quality
      assurance aspects for commercially available CT-based IGRT, each with their
      unique capabilities and underlying physics. The systems described are kilovolt
      and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the
      literature describing current clinical usage is also provided. RESULTS: This
      report proposes a generic quality assurance program for CT-based IGRT systems in
      an effort to provide a vendor-independent program for clinical users. Published
      data from long-term, repeated quality control tests form the basis of the
      proposed test frequencies and tolerances. CONCLUSION: A program for quality
      control of CT-based image-guidance systems has been produced, with focus on
      geometry, image quality, image dose, system operation, and safety. Agreement and
      clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and
      TG-148 has been addressed.

PMID- 22482617
TI  - Correction factors for A1SL ionization chamber dosimetry in TomoTherapy: machine
      specific, plan-class, and clinical fields.
AB  - PURPOSE: Recently, an international working group on nonstandard fields presented
      a new formalism for ionization chamber reference dosimetry of small and
      nonstandard fields [Alfonso et al., Med. Phys. 35, 5179-5186 (2008)] which has
      been adopted by AAPM TG-148. This work presents an experimental determination of
      the correction factors for reference dosimetry with an Exradin A1SL thimble
      ionization chamber in a TomoTherapy unit, focusing on: (i) machine-specific
      reference field, (ii) plan-class-specific reference field, and (iii) two clinical
      treatments. METHODS: Ionization chamber measurements were performed in the
      TomoTherapy unit for intermediate (machine-specific and plan-class-specific)
      calibration fields, based on the reference conditions defined by AAPM TG-148, and
      two clinical treatments (lung and head-and-neck). Alanine reference dosimetry was
      employed to determine absorbed dose to water at the point of interest for the
      fields under investigation. The corresponding chamber correction factors were
      calculated from alanine to ionization chamber measurements ratios. RESULTS: Two
      different methods of determining the beam quality correction factor k(Q,Q(0) )
      for the A1SL ionization chamber in this TomoTherapy unit, where reference
      conditions for conventional beam quality determination cannot be met, result in
      consistent values. The observed values of overall correction factors obtained for
      intermediate and clinical fields are consistently around 0.98 with a typical
      expanded relative uncertainty of 2% (k = 2), which when considered make such
      correction factors compatible with unity. However, all of them are systematically
      lower than unity, which is shown to be significant when a hypothesis test
      assuming a t-student distribution is performed (p=1.8*10(-2)). Correction factors
      k(Q(clin),Q(pcsr) ) (f(clin),f(pcsr) ) and k(Q(clin),Q(msr) ) (f(clin),f(msr) ),
      which are needed for the computation of field factors for relative dosimetry of
      clinical beams, have been found to be very close to unity for two clinical
      treatments. CONCLUSIONS: The results indicate that the helical field deliveries
      in this study (including two clinical fields) do not introduce changes on the ion
      chamber correction factors for dosimetry. For those two specific clinical cases,
      ratios of chamber readings accurately represent field output factors. The values
      observed here for intermediate calibration fields are in agreement with
      previously published data based on alanine dosimetry but differ from values
      recently reported obtained via radiochromic dosimetry.

PMID- 22482618
TI  - Characteristics of miniature electronic brachytherapy x-ray sources based on TG
      43U1 formalism using Monte Carlo simulation techniques.
AB  - PURPOSE: The goal of this study is to determine a method for Monte Carlo (MC)
      characterization of the miniature electronic brachytherapy x-ray sources (MEBXS)
      and to set dosimetric parameters according to TG-43U1 formalism. TG-43U1
      parameters were used to get optimal designs of MEBXS. Parameters that affect the
      dose distribution such as anode shapes, target thickness, target angles, and
      electron beam source characteristics were evaluated. Optimized MEBXS designs were
      obtained and used to determine radial dose functions and 2D anisotropy functions
      in the electron energy range of 25-80 keV. METHODS: Tungsten anode material was
      considered in two different geometries, hemispherical and conical-hemisphere.
      These configurations were analyzed by the 4C MC code with several different
      optimization techniques. The first optimization compared target thickness layers
      versus electron energy. These optimized thicknesses were compared with published
      results by Ihsan et al. [Nucl. Instrum. Methods Phys. Res. B 264, 371-377
      (2007)]. The second optimization evaluated electron source characteristics by
      changing the cathode shapes and electron energies. Electron sources studied
      included; (1) point sources, (2) uniform cylinders, and (3) nonuniform
      cylindrical shell geometries. The third optimization was used to assess the apex
      angle of the conical-hemisphere target. The goal of these optimizations was to
      produce 2D-dose anisotropy functions closer to unity. An overall optimized MEBXS
      was developed from this analysis. The results obtained from this model were
      compared to known characteristics of HDR (125)I, LDR (103)Pd, and Xoft AxxentTM
      electronic brachytherapy source (XAEBS) [Med. Phys. 33, 4020-4032 (2006)].
      RESULTS: The optimized anode thicknesses as a function of electron energy is
      fitted by the linear equation Y (MUm) = 0.0459X (keV)-0.7342. The optimized
      electron source geometry is obtained for a disk-shaped parallel beam (uniform
      cylinder) with 0.9 mm radius. The TG-43 distribution is less sensitive to the
      shape of the conical-hemisphere anode than the hemispherical anode. However, the
      optimized apex angle of conical-hemisphere anode was determined to be 60 degrees
      . For the hemispherical targets, calculated radial dose function values at a
      distance of 5 cm were 0.137, 0.191, 0.247, and 0.331 for 40, 50, 60, and 80 keV
      electrons, respectively. These values for the conical-hemisphere targets are
      0.165, 0.239, 0.305, and 0.412, respectively. Calculated 2D anisotropy functions
      values for the hemispherical target shape were F(1 cm, 0 degrees ) = 1.438 and
      F(1 cm, 0 degrees ) = 1.465 for 30 and 80 keV electrons, respectively. The
      corresponding values for conical-hemisphere targets are 1.091 and 1.241,
      respectively. CONCLUSIONS: A method for the characterizations of MEBXS using TG
      43U1 dosimetric data using the MC MCNP4C has been presented. The effects of
      target geometry, thicknesses, and electron source geometry have been
      investigated. The final choices of MEBXS design are conical-hemisphere target
      shapes having an apex angle of 60 degrees . Tungsten material having an optimized
      thickness versus electron energy and a 0.9 mm radius of uniform cylinder as a
      cathode produces optimal electron source characteristics.

PMID- 22482619
TI  - Dosimetric and thermal properties of a newly developed thermobrachytherapy seed
      with ferromagnetic core for treatment of solid tumors.
AB  - PURPOSE: Studies of the curative effects of hyperthermia and radiation therapy on
      treatment of cancer show a strong evidence of a synergistic enhancement when both
      radiation and hyperthermia modalities are applied simultaneously. Varieties of
      tissue heating approaches developed up to date still fail to overcome such
      essential limitations as an inadequate temperature control, temperature
      nonuniformity, and prolonged time delay between hyperthermia and radiation
      treatments. The authors propose a new self-regulating thermobrachytherapy seed,
      which serves as a source of both radiation and heat for concurrent administration
      of brachytherapy and hyperthermia. METHODS: The proposed seed is based on the
      BEST Medical, Inc., Seed Model 2301-I(125), where tungsten marker core and the
      air gap are replaced with a ferromagnetic material. The ferromagnetic core
      produces heat when subjected to alternating electromagnetic (EM) field and
      effectively shuts off after reaching the Curie temperature (T(C)) of the
      ferromagnetic material thus realizing the temperature self-regulation. The
      authors present a Monte Carlo study of the dose rate constant and other TG-43
      factors for the proposed seed. For the thermal characteristics, the authors
      studied a model consisting of 16 seeds placed in the central region of a
      cylindrical water phantom using a finite-element partial differential equation
      solver package "COMSOL Multiphysics." RESULTS: The modification of the internal
      structure of the seed slightly changes dose rate and other TG-43 factors
      characterizing radiation distribution. The thermal modeling results show that the
      temperature of the thermoseed surface rises rapidly and stays constant around
      T(C) of the ferromagnetic material. The amount of heat produced by the
      ferromagnetic core is sufficient to raise the temperature of the surrounding
      phantom to the therapeutic range. The phantom volume reaching the therapeutic
      temperature range increases with increase in frequency or magnetic field
      strength. CONCLUSIONS: An isothermal distribution matching with the radiation
      isodose distribution can be achieved within a target volume by tuning frequency
      and intensity of the alternating magnetic field. The proposed combination seed
      model has a potential for implementation of concurrent brachytherapy and
      hyperthermia.

PMID- 22482620
TI  - Quantitative cone-beam CT imaging in radiation therapy using planning CT as a
      prior: first patient studies.
AB  - PURPOSE: Quantitative cone-beam CT (CBCT) imaging is on increasing demand for
      high-performance image guided radiation therapy (IGRT). However, the current CBCT
      has poor image qualities mainly due to scatter contamination. Its current
      clinical application is therefore limited to patient setup based on only bony
      structures. To improve CBCT imaging for quantitative use, we recently proposed a
      correction method using planning CT (pCT) as the prior knowledge. Promising
      phantom results have been obtained on a tabletop CBCT system, using a correction
      scheme with rigid registration and without iterations. More challenges arise in
      clinical implementations of our method, especially because patients have large
      organ deformation in different scans. In this paper, we propose an improved
      framework to extend our method from bench to bedside by including several new
      components. METHODS: The basic principle of our correction algorithm is to
      estimate the primary signals of CBCT projections via forward projection on the
      pCT image, and then to obtain the low-frequency errors in CBCT raw projections by
      subtracting the estimated primary signals and low-pass filtering. We improve the
      algorithm by using deformable registration to minimize the geometry difference
      between the pCT and the CBCT images. Since the registration performance relies on
      the accuracy of the CBCT image, we design an optional iterative scheme to update
      the CBCT image used in the registration. Large correction errors result from the
      mismatched objects in the pCT and the CBCT scans. Another optional step of gas
      pocket and couch matching is added into the framework to reduce these effects.
      RESULTS: The proposed method is evaluated on four prostate patients, of which two
      cases are presented in detail to investigate the method performance for a large
      variety of patient geometry in clinical practice. The first patient has small
      anatomical changes from the planning to the treatment room. Our algorithm works
      well even without the optional iterations and the gas pocket and couch matching.
      The image correction on the second patient is more challenging due to the effects
      of gas pockets and attenuating couch. The improved framework with all new
      components is used to fully evaluate the correction performance. The enhanced
      image quality has been evaluated using mean CT number and spatial nonuniformity
      (SNU) error as well as contrast improvement factor. If the pCT image is
      considered as the ground truth, on the four patients, the overall mean CT number
      error is reduced from over 300 HU to below 16 HU in the selected regions of
      interest (ROIs), and the SNU error is suppressed from over 18% to below 2%. The
      average soft-tissue contrast is improved by an average factor of 2.6.
      CONCLUSIONS: We further improve our pCT-based CBCT correction algorithm for
      clinical use. Superior correction performance has been demonstrated on four
      patient studies. By providing quantitative CBCT images, our approach
      significantly increases the accuracy of advanced CBCT-based clinical applications
      for IGRT.

PMID- 22482621
TI  - A computerized scheme for lung nodule detection in multiprojection chest
      radiography.
AB  - PURPOSE: Our previous study indicated that multiprojection chest radiography
      could significantly improve radiologists' performance for lung nodule detection
      in clinical practice. In this study, the authors further verify that
      multiprojection chest radiography can greatly improve the performance of a
      computer-aided diagnostic (CAD) scheme. METHODS: Our database consisted of 59
      subjects, including 43 subjects with 45 nodules and 16 subjects without nodules.
      The 45 nodules included 7 real and 38 simulated ones. The authors developed a
      conventional CAD scheme and a new fusion CAD scheme to detect lung nodules. The
      conventional CAD scheme consisted of four steps for (1) identification of initial
      nodule candidates inside lungs, (2) nodule candidate segmentation based on
      dynamic programming, (3) extraction of 33 features from nodule candidates, and
      (4) false positive reduction using a piecewise linear classifier. The
      conventional CAD scheme processed each of the three projection images of a
      subject independently and discarded the correlation information between the three
      images. The fusion CAD scheme included the four steps in the conventional CAD
      scheme and two additional steps for (5) registration of all candidates in the
      three images of a subject, and (6) integration of correlation information between
      the registered candidates in the three images. The integration step retained all
      candidates detected at least twice in the three images of a subject and removed
      those detected only once in the three images as false positives. A leave-one
      subject-out testing method was used for evaluation of the performance levels of
      the two CAD schemes. RESULTS: At the sensitivities of 70%, 65%, and 60%, our
      conventional CAD scheme reported 14.7, 11.3, and 8.6 false positives per image,
      respectively, whereas our fusion CAD scheme reported 3.9, 1.9, and 1.2 false
      positives per image, and 5.5, 2.8, and 1.7 false positives per patient,
      respectively. The low performance of the conventional CAD scheme may be
      attributed to the high noise level in chest radiography, and the small size and
      low contrast of most nodules. CONCLUSIONS: This study indicated that the fusion
      of correlation information in multiprojection chest radiography can markedly
      improve the performance of CAD scheme for lung nodule detection.

PMID- 22482622
TI  - A comparison of physical and dosimetric properties of lung substitute materials.
AB  - PURPOSE: The need for an accurate estimate of absorbed doses within and around
      irradiated thorax tissues necessitates the use of carefully selected materials
      from which phantoms are constructed. A lung substitute is more difficult to
      establish mostly due to its low physical density. Although many researchers have
      used cork as a lung substitute, very little research data address cork's
      characteristics to determine which type of cork is optimal as a substitute for
      lung tissue. METHODS: Natural cork, composition cork, rubber cork, ATOM, RANDO,
      and a reference lung material (ICRU-44 lung tissue) were investigated to
      establish comparisons of physical properties. Following the determination of the
      respective physical properties, the dose distributions from 6 MV photon beams in
      water/lung substitute/water phantoms were assessed using the Monte Carlo method.
      Physical and electron densities affecting the dose distributions through lung
      tissues in different field size conditions were investigated. RESULTS: The
      physical properties (physical density, electronic density, and effective atomic
      number) of the composition cork are the most similar to those of the ICRU-44
      lung, and the CT number of the composition cork is very similar to that of humans
      aged 30-60. PDD of the composition cork and the RANDO phantom are the most
      comparable to that of ICRU-44 lung in 1 * 1 cm(2) field size due to the combined
      properties of physical density (PD) and electron density per gram (EDG) of the
      studied lung materials. PD and EDG affect the lung dose primarily in small field
      size. The effects of PD are minimal in large fields, having a more rapid lateral
      electron equilibrium. EDG dominates PDD pattern in lung material when large
      fields are applied. Combined effects of PD and EDG are nonlinear for all field
      sizes. CONCLUSIONS: The composition cork is the preferred lung substitute based
      on physical and dosimetric properties.

PMID- 22482623
TI  - Potential of dual-energy subtraction for converting CT numbers to electron
      density based on a single linear relationship.
AB  - PURPOSE: The conversion of the computed tomography (CT) number to electron
      density is one of the main processes that determine the accuracy of patient dose
      calculations in radiotherapy treatment planning. However, the CT number and
      electron density of tissues cannot be generally interrelated via a simple one-to
      one correspondence because the CT number depends on the effective atomic number
      as well as the electron density. The purpose of this study is to present a simple
      conversion from the energy-subtracted CT number (DeltaHU) by means of dual-energy
      CT (DECT) to the relative electron density (rho(e)) via a single linear
      relationship. METHODS: The DeltaHU-rho(e) conversion method was demonstrated by
      performing analytical DECT image simulations that were intended to imitate a
      second-generation dual-source CT (DSCT) scanner with an additional tin filtration
      for the high-kV tube. The DeltaHU-rho(e) calibration line was obtained from the
      image simulation with a 33 cm-diameter electron density calibration phantom
      equipped with 16 inserts including polytetrafluoroethylene, polyvinyl chloride,
      and aluminum; the elemental compositions of these three inserts were quite
      different to those of body tissues. The DeltaHU-rho(e) conversion method was also
      applied to previously published experimental CT data, which were measured using
      two different CT scanners, to validate the clinical feasibility of the present
      approach. In addition, the effect of object size on rho(e)-calibrated images was
      investigated by image simulations using a 25 cm-diameter virtual phantom for two
      different filtrations: with and without the tin filter for the high-kV tube.
      RESULTS: The simulated DeltaHU-rho(e) plot exhibited a predictable linear
      relationship over a wide range of rho(e) from 0.00 (air) to 2.35 (aluminum).
      Resultant values of the coefficient of determination, slope, and intercept of the
      linear function fitted to the data were close to those of the ideal case. The
      maximum difference between the ideal and simulated rho(e) values was -0.7%. The
      satisfactory linearity of DeltaHU-rho(e) was also confirmed from analyses of the
      experimental CT data. In the experimental cases, the maximum difference between
      the nominal and simulated rho(e) values was found to be 2.5% after two outliers
      were excluded. When compared with the case without the tin filter, the DeltaHU
      rho(e) conversion performed with the tin filter yielded a lower dose and more
      reliable rho(e) values that were less affected by the object-size variation.
      CONCLUSIONS: The DeltaHU-rho(e) calibration line with a simple one-to-one
      correspondence would facilitate the construction of a well-calibrated rho(e)
      image from acquired dual-kV images, and currently, second generation DSCT may be
      a feasible modality for the clinical use of the DeltaHU-rho(e) conversion method.

PMID- 22482624
TI  - A realistic deformable prostate phantom for multimodal imaging and needle
      insertion procedures.
AB  - PURPOSE: Phantoms are a vital step for the preliminary validation of new image
      guided procedures. In this paper, the authors present a deformable prostate
      phantom for use with multimodal imaging (end-fire or side-fire ultrasound, CT and
      MRI) and more specifically for transperineal or transrectal needle-insertion
      procedures. It is made of soft polyvinyl chloride (PVC) plastic and includes a
      prostate, a perineum, a rectum, a soft periprostatic surrounding and embedded
      targets for image registration and needle-targeting. Its main particularity is
      its realistic deformability upon manipulation. METHODS: After a detailed
      manufacturing description, the imaging and mechanical characteristics of the
      phantom are described and evaluated. First, the speed of sound and stress-strain
      relationship of the PVC material used in the phantom are described, followed by
      an analysis of its storage, imaging, needle-insertion force, and deformability
      characteristics. RESULTS: The average speed of sound in the phantom was measured
      to be 1380 +/- 20 m/s, while the stress-strain relationship was found to be
      viscoelastic and in the range of typical prostatic tissues. The mechanical and
      imaging characteristics of the phantom were found to remain stable at cooler
      storage temperatures. The phantom had clearly distinguishable morphology in all
      three imaging modalities, with embedded targets that could be precisely
      segmented, resulting in an average US-CT rigid registration error of 0.66 mm. The
      mobility of the phantom prostate upon needle insertion was between 2 and 4 mm,
      with rotations between 0 degrees  and 2 degrees , about the US probe head.
      CONCLUSION: The phantom's characteristics compare favorably with in vitro and in
      vivo measurements found in the literature. The authors believe that this
      realistic phantom could be of use to researchers studying new needle-based
      prostate diagnosis and therapy techniques.

PMID- 22482625
TI  - Online monitoring and error detection of real-time tumor displacement prediction
      accuracy using control limits on respiratory surrogate statistics.
AB  - PURPOSE: To evaluate Hotelling's T(2) statistic and the input variable squared
      prediction error (Q((X))) for detecting large respiratory surrogate-based tumor
      displacement prediction errors without directly measuring the tumor's position.
      METHODS: Tumor and external marker positions from a database of 188 Cyberknife
      SynchronyTM lung, liver, and pancreas treatment fractions were analyzed. The
      first ten measurements of tumor position in each fraction were used to create
      fraction-specific models of tumor displacement using external surrogates as
      input; the models were used to predict tumor position from subsequent external
      marker measurements. A partial least squares (PLS) model with four scores was
      developed for each fraction to determine T(2) and Q((X)) confidence limits based
      on the first ten measurements in a fraction. The T(2) and Q((X)) statistics were
      then calculated for every set of external marker measurements. Correlations
      between model error and both T(2) and Q((X)) were determined. Receiver operating
      characteristic analysis was applied to evaluate sensitivities and specificities
      of T(2), Q((X)), and T(2)?Q((X)) for predicting real-time tumor localization
      errors >3 mm over a range of T(2) and Q((X)) confidence limits. RESULTS:
      Sensitivity and specificity of detecting errors >3 mm varied with confidence
      limit selection. At 95% sensitivity, T(2)?Q((X)) specificity was 15%, 2% higher
      than either T(2) or Q((X)) alone. The mean time to alarm for T(2)?Q((X)) at 95%
      sensitivity was 5.3 min but varied with a standard deviation of 8.2 min. Results
      did not differ significantly by tumor site. CONCLUSIONS: The results of this
      study establish the feasibility of respiratory surrogate-based online monitoring
      of real-time respiration-induced tumor motion model accuracy for lung, liver, and
      pancreas tumors. The T(2) and Q((X)) statistics were able to indicate whether
      inferential model errors exceeded 3 mm with high sensitivity. Modest improvements
      in specificity were achieved by combining T(2) and Q((X)) results.

PMID- 22482626
TI  - Improving the sensitivity of high-frequency subharmonic imaging with coded
      excitation: a feasibility study.
AB  - PURPOSE: Subharmonic intravascular ultrasound imaging (S-IVUS) could visualize
      the adventitial vasa vasorum, but the high pressure threshold required to incite
      subharmonic behavior in an ultrasound contrast agent will compromise sensitivity
      a trait that has hampered the clinical use of S-IVUS. The purpose of this study
      was to assess the feasibility of using coded-chirp excitations to improve the
      sensitivity and axial resolution of S-IVUS. METHODS: The subharmonic response of
      Targestar-p(TM), a commercial microbubble ultrasound contrast agent (UCA), to
      coded-chirp (5%-20% fractional bandwidth) pulses and narrowband sine-burst (4%
      fractional bandwidth) pulses was assessed, first using computer simulations and
      then experimentally. Rectangular windowed excitation pulses with pulse durations
      ranging from 0.25 to 3 MUs were used in all studies. All experimental studies
      were performed with a pair of transducers (20 MHz/10 MHz), both with diameter of
      6.35 mm and focal length of 50 mm. The size distribution of the UCA was measured
      with a Casy(TM) Cell counter. RESULTS: The simulation predicted a pressure
      threshold that was an order of magnitude higher than that determined
      experimentally. However, all other predictions were consistent with the
      experimental observations. It was predicted that: (1) exciting the agent with
      chirps would produce stronger subharmonic response relative to those produced by
      sine-bursts; (2) increasing the fractional bandwidth of coded-chirp excitation
      would increase the sensitivity of subharmonic imaging; and (3) coded-chirp would
      increase axial resolution. The experimental results revealed that subharmonic-to
      fundamental ratios obtained with chirps were 5.7 dB higher than those produced
      with sine-bursts of similar duration. The axial resolution achieved with 20%
      fractional bandwidth chirps was approximately twice that achieved with 4%
      fractional bandwidth sine-bursts. CONCLUSIONS: The coded-chirp method is a
      suitable excitation strategy for subharmonic IVUS imaging. At the 20 MHz
      transmission frequency and 20% fractional bandwidth, coded-chirp excitation
      appears to represent the ideal tradeoff between subharmonic strength and axial
      resolution.

PMID- 22482627
TI  - CT, MR, and ultrasound image artifacts from prostate brachytherapy seed implants:
      the impact of seed size.
AB  - PURPOSE: To investigate the effects of brachytherapy seed size on the quality of
      x-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR)
      images and seed localization through comparison of the 6711 and 9011 (125)I
      sources. METHODS: For CT images, an acrylic phantom mimicking a clinical
      implantation plan and embedded with low contrast regions of interest (ROIs) was
      designed for both the 0.774 mm diameter 6711 (standard) and the 0.508 mm diameter
      9011 (thin) seed models (Oncura, Inc., and GE Healthcare, Arlington Heights, IL).
      Image quality metrics were assessed using the standard deviation of ROIs between
      the seeds and the contrast to noise ratio (CNR) within the low contrast ROIs. For
      US images, water phantoms with both single and multiseed arrangements were
      constructed for both seed sizes. For MR images, both seeds were implanted into a
      porcine gel and imaged with pelvic imaging protocols. The standard deviation of
      ROIs and CNR values were used as metrics of artifact quantification. Seed
      localization within the CT images was assessed using the automated seed finder in
      a commercial brachytherapy treatment planning system. The number of erroneous
      seed placements and the average and maximum error in seed placements were
      recorded as metrics of the localization accuracy. RESULTS: With the thin seeds,
      CT image noise was reduced from 48.5 +/- 0.2 to 32.0 +/- 0.2 HU and CNR improved
      by a median value of 74% when compared with the standard seeds. Ultrasound image
      noise was measured at 50.3 +/- 17.1 dB for the thin seed images and 50.0 +/- 19.8
      dB for the standard seed images, and artifacts directly behind the seeds were
      smaller and less prominent with the thin seed model. For MR images, CNR of the
      standard seeds reduced on average 17% when using the thin seeds for all different
      imaging sequences and seed orientations, but these differences are not
      appreciable. Automated seed localization required an average (+/-SD) of 7.0 +/-
      3.5 manual corrections in seed positions for the thin seed scans and 3.0 +/- 1.2
      manual corrections in seed positions for the standard seed scans. The average
      error in seed placement was 1.2 mm for both seed types and the maximum error in
      seed placement was 2.1 mm for the thin seed scans and 1.8 mm for the standard
      seed scans. CONCLUSIONS: The 9011 thin seeds yielded significantly improved image
      quality for CT and US images but no significant differences in MR image quality.

PMID- 22482628
TI  - Monte Carlo simulation of breast imaging using synchrotron radiation.
AB  - PURPOSE: Synchrotron radiation (SR), being the brightest artificial source of x
      rays with a very promising geometry, has raised the scientific expectations that
      it could be used for breast imaging with optimized results. The "in situ"
      evaluation of this technique is difficult to perform, mostly due to the limited
      available SR facilities worldwide. In this study, a simulation model for SR
      breast imaging was developed, based on Monte Carlo simulation techniques, and
      validated using data acquired in the SYRMEP beamline of the Elettra facility in
      Trieste, Italy. Furthermore, primary results concerning the performance of SR
      were derived. METHODS: The developed model includes the exact setup of the SR
      beamline, considering that the x-ray source is located at almost 23 m from the
      slit, while the photon energy was considered to originate from a very narrow
      Gaussian spectrum. Breast phantoms, made of Perspex and filled with air cavities,
      were irradiated with energies in the range of 16-28 keV. The model included a
      Gd(2)O(2)S detector with the same characteristics as the one available in the
      SYRMEP beamline. Following the development and validation of the model,
      experiments were performed in order to evaluate the contrast resolution of SR. A
      phantom made of adipose tissue and filled with inhomogeneities of several
      compositions and sizes was designed and utilized to simulate the irradiation
      under conventional mammography and SR conditions. RESULTS: The validation results
      of the model showed an excellent agreement with the experimental data, with the
      correlation for contrast being 0.996. Significant differences only appeared at
      the edges of the phantom, where phase effects occur. The initial evaluation
      experiments revealed that SR shows very good performance in terms of the image
      quality indices utilized, namely subject contrast and contrast to noise ratio.
      The response of subject contrast to energy is monotonic; however, this does not
      stand for contrast to noise ratio, since there is a range of optimal performance
      for SR (18-21 keV). In comparison to conventional mammography, SR shows improved
      subject contrast for energies lower than the mean energy of each spectrum.
      CONCLUSIONS: The comparison of the results of the two models, conventional and
      SR, proved that SR exhibits better performance in the majority of cases. The
      proposed simulation model offers the possibility to perform exhaustive search to
      evaluate the performance of SR in clinical applications such as breast imaging.

PMID- 22482629
TI  - A novel energy mapping approach for CT-based attenuation correction in PET.
AB  - PURPOSE: Dual-energy CT (DECT) is arguably the most accurate energy mapping
      technique in CT-based attenuation correction (CTAC) implemented on hybrid PET/CT
      systems. However, this approach is not attractive for clinical use owing to
      increased patient dose. The authors propose a novel energy mapping approach
      referred to as virtual DECT (VDECT) taking advantage of the DECT formulation but
      using CT data acquired at a single energy (kV(P)). For this purpose, the CT image
      acquired at one energy is used to generate the CT image at a second energy using
      calculated kV(P) conversion curves derived from phantom studies. METHODS: The
      attenuation map (MU-map) at 511 keV was generated for the XCAT phantom and
      clinical studies using the bilinear, DECT, and VDECT techniques. The generated MU
      maps at 511 keV are compared to the reference derived from the XCAT phantom
      serving as ground truth. PET data generated from a predefined activity map for
      the XCAT phantom were then corrected for attenuation using MU-maps generated
      using the different energy mapping approaches. In addition, the generated MU-maps
      using the above described methods for a cylindrical polyethylene phantom
      containing different concentrations of K(2)HPO(4) in water were compared to
      actual attenuation coefficients. Likewise, CT images of five clinical whole-body
      studies were used to generate MU-maps using the various energy-mapping approaches
      were compared with MU-maps acquired at 511 keV using (68)Ge/(68)Ga rod sources
      for the clinical studies. RESULTS: The results of phantom studies demonstrate
      that the proposed method is more accurate than the bilinear technique. All three
      MU-maps yielded almost similar results for soft and lung tissues whereas for bone
      tissues, the DECT and the VDECT methods produced a much smaller mean relative
      difference (3.0% and 2.8%, respectively) than the bilinear approach (11.8%).
      Likewise, the comparison of PET images corrected for attenuation using the
      various methods showed that the proposed method provides better accuracy (6.5%)
      than the bilinear method (13.4%). Clinical studies further demonstrated that,
      compared to the bilinear method, the VDECT approach has better agreement for bony
      structures with the DECT technique (1.5% versus 8.9%) and transmission scanning
      (8.8% versus 17.7%). CONCLUSIONS: It was concluded that the proposed method
      outperforms the bilinear method especially in bony structures. Further evaluation
      using a large clinical PET/CT database is underway to evaluate the potential of
      the technique in a clinical setting.

PMID- 22482630
TI  - High resolution stationary digital breast tomosynthesis using distributed carbon
      nanotube x-ray source array.
AB  - PURPOSE: The purpose of this study is to investigate the feasibility of
      increasing the system spatial resolution and scanning speed of Hologic Selenia
      Dimensions digital breast tomosynthesis (DBT) scanner by replacing the rotating
      mammography x-ray tube with a specially designed carbon nanotube (CNT) x-ray
      source array, which generates all the projection images needed for tomosynthesis
      reconstruction by electronically activating individual x-ray sources without any
      mechanical motion. The stationary digital breast tomosynthesis (s-DBT) design
      aims to (i) increase the system spatial resolution by eliminating image blurring
      due to x-ray tube motion and (ii) reduce the scanning time. Low spatial
      resolution and long scanning time are the two main technical limitations of
      current DBT technology. METHODS: A CNT x-ray source array was designed and
      evaluated against a set of targeted system performance parameters. Simulations
      were performed to determine the maximum anode heat load at the desired focal spot
      size and to design the electron focusing optics. Field emission current from CNT
      cathode was measured for an extended period of time to determine the stable life
      time of CNT cathode for an expected clinical operation scenario. The source array
      was manufactured, tested, and integrated with a Selenia scanner. An electronic
      control unit was developed to interface the source array with the detection
      system and to scan and regulate x-ray beams. The performance of the s-DBT system
      was evaluated using physical phantoms. RESULTS: The spatially distributed CNT x
      ray source array comprised 31 individually addressable x-ray sources covering a
      30 angular span with 1 pitch and an isotropic focal spot size of 0.6 mm at full
      width at half-maximum. Stable operation at 28 kV(peak) anode voltage and 38 mA
      tube current was demonstrated with extended lifetime and good source-to-source
      consistency. For the standard imaging protocol of 15 views over 14, 100 mAs dose,
      and 2 * 2 detector binning, the projection resolution along the scanning
      direction increased from 4.0 cycles/mm [at 10% modulation-transfer-function
      (MTF)] in DBT to 5.1 cycles/mm in s-DBT at magnification factor of 1.08. The
      improvement is more pronounced for faster scanning speeds, wider angular
      coverage, and smaller detector pixel sizes. The scanning speed depends on the
      detector, the number of views, and the imaging dose. With 240 ms detector readout
      time, the s-DBT system scanning time is 6.3 s for a 15-view, 100 mAs scan
      regardless of the angular coverage. The scanning speed can be reduced to less
      than 4 s when detectors become faster. Initial phantom studies showed good
      quality reconstructed images. CONCLUSIONS: A prototype s-DBT scanner has been
      developed and evaluated by retrofitting the Selenia rotating gantry DBT scanner
      with a spatially distributed CNT x-ray source array. Preliminary results show
      that it improves system spatial resolution substantially by eliminating image
      blur due to x-ray focal spot motion. The scanner speed of s-DBT system is
      independent of angular coverage and can be increased with faster detector without
      image degration. The accelerated lifetime measurement demonstrated the long term
      stability of CNT x-ray source array with typical clinical operation lifetime over
      3 years.

PMID- 22482631
TI  - Development of array-type prompt gamma measurement system for in vivo range
      verification in proton therapy.
AB  - PURPOSE: In vivo range verification is one of the most important parts of proton
      therapy to fully utilize its benefits delivering high radiation dose to tumor,
      while sparing the normal tissue with the so-called Bragg peak. Currently,
      however, range verification method is not used in clinics. The purpose of the
      present study is to optimize and evaluate the configuration of an array-type
      prompt gamma measurement system on determining distal dose edge for in vivo range
      verification of proton therapy. METHODS: To effectively measure the prompt gammas
      against the background gammas, the Monte Carlo simulations with the MCNPX code
      were employed in optimizing the configuration of the measurement system, and the
      Monte Carlo method was also used to understand the effect of the background
      gammas, mainly neutron capture gammas, in the measured gamma distribution. To
      reduce the effect of the background gammas, the optimized energy window of 4-10
      MeV in measuring the prompt gammas was employed. A parameterized source was used
      to maximize computation speed in the optimization study. A simplified test
      measurement system, using only one detector moving from one measurement location
      to the next, was constructed and applied to therapeutic proton beams of 80-220
      MeV. For accurate determination of the distal dose edge, the sigmoidal curve
      fitting method was applied to the measured distributions of the prompt gammas,
      and then, the location of the half-value between the maximum and minimum value in
      the curve-fitting was determined as the distal dose edge and compared with the
      beam range assessed by the proton dose distribution. RESULTS: The parameterized
      source term employed in optimization process improved the calculation speed by up
      to ~300 times. The optimization study indicates that an array-type measurement
      system with 3, 2, 2, and 150 mm for scintillator thickness, slit width, septal
      thickness, and slit length, respectively, can effectively measure the prompt
      gamma distributions minimizing the contribution of background gammas. The present
      results show that a few hundred counts of prompt gammas can be easily obtained by
      measuring 10 s at each measurement location for proton beams of ~4 nA. The distal
      dose edges determined by the prompt gamma distribution are 5.45, 14.73, and 27.74
      cm for proton beams of 5.17 (80 MeV), 14.99 (150 MeV), and 27.38 (220 MeV) cm,
      respectively. CONCLUSIONS: The results show that the array-type measurement
      system can measure prompt gamma distributions from a therapeutic proton beam
      within a short measurement time, and that the distal dose edge can be determined
      within a few millimeters of error without using any sophisticated analysis.

PMID- 22482632
TI  - A semiempirical linear model of indirect, flat-panel x-ray detectors.
AB  - PURPOSE: It is important to understand signal and noise transfer in the indirect,
      flat-panel x-ray detector when developing and optimizing imaging systems. For
      optimization where simulating images is necessary, this study introduces a
      semiempirical model to simulate projection images with user-defined x-ray fluence
      interaction. METHODS: The signal and noise transfer in the indirect, flat-panel x
      ray detectors is characterized by statistics consistent with energy-integration
      of x-ray photons. For an incident x-ray spectrum, x-ray photons are attenuated
      and absorbed in the x-ray scintillator to produce light photons, which are
      coupled to photodiodes for signal readout. The signal mean and variance are
      linearly related to the energy-integrated x-ray spectrum by empirically
      determined factors. With the known first- and second-order statistics, images can
      be simulated by incorporating multipixel signal statistics and the modulation
      transfer function of the imaging system. To estimate the semiempirical input to
      this model, 500 projection images (using an indirect, flat-panel x-ray detector
      in the breast CT system) were acquired with 50-100 kilovolt (kV) x-ray spectra
      filtered with 0.1-mm tin (Sn), 0.2-mm copper (Cu), 1.5-mm aluminum (Al), or 0.05
      mm silver (Ag). The signal mean and variance of each detector element and the
      noise power spectra (NPS) were calculated and incorporated into this model for
      accuracy. Additionally, the modulation transfer function of the detector system
      was physically measured and incorporated in the image simulation steps. For
      validation purposes, simulated and measured projection images of air scans were
      compared using 40 kV/0.1-mm Sn, 65 kV/0.2-mm Cu, 85 kV/1.5-mm Al, and 95 kV/0.05
      mm Ag. RESULTS: The linear relationship between the measured signal statistics
      and the energy-integrated x-ray spectrum was confirmed and incorporated into the
      model. The signal mean and variance factors were linearly related to kV for each
      filter material (r(2) of signal mean to kV: 0.91, 0.93, 0.86, and 0.99 for 0.1-mm
      Sn, 0.2-mm Cu, 1.5-mm Al, and 0.05-mm Ag, respectively; r(2) of signal variance
      to kV: 0.99 for all four filters). The comparison of the signal and noise (mean,
      variance, and NPS) between the simulated and measured air scan images suggested
      that this model was reasonable in predicting accurate signal statistics of air
      scan images using absolute percent error. Overall, the model was found to be
      accurate in estimating signal statistics and spatial correlation between the
      detector elements of the images acquired with indirect, flat-panel x-ray
      detectors. CONCLUSIONS: The semiempirical linear model of the indirect, flat
      panel x-ray detectors was described and validated with images of air scans. The
      model was found to be a useful tool in understanding the signal and noise
      transfer within indirect, flat-panel x-ray detector systems.

PMID- 22482633
TI  - A method to evaluate dose errors introduced by dose mapping processes for mass
      conserving deformations.
AB  - PURPOSE: To present a method to evaluate the dose mapping error introduced by the
      dose mapping process. In addition, apply the method to evaluate the dose mapping
      error introduced by the 4D dose calculation process implemented in a research
      version of commercial treatment planning system for a patient case. METHODS: The
      average dose accumulated in a finite volume should be unchanged when the dose
      delivered to one anatomic instance of that volume is mapped to a different
      anatomic instance-provided that the tissue deformation between the anatomic
      instances is mass conserving. The average dose to a finite volume on image S is
      defined as d(S)=e(s)/m(S), where e(S) is the energy deposited in the mass m(S)
      contained in the volume. Since mass and energy should be conserved, when d(S) is
      mapped to an image R(d(S->R)=d(R)), the mean dose mapping error is defined as
      Deltad(m)=|d(R)-d(S)|=|e(R)/m(R)-e(S)/m(S)|, where the e(R) and e(S) are integral
      doses (energy deposited), and m(R) and m(S) are the masses within the region of
      interest (ROI) on image R and the corresponding ROI on image S, where R and S are
      the two anatomic instances from the same patient. Alternatively, application of
      simple differential propagation yields the differential dose mapping error,
      Deltad(d)=|?d?e*Deltae+?d?m*Deltam|=|(e(S)-e(R))m(R)-(m(S)-m(R))m(R)
      (2)*e(R)|=alpha|d(R)-d(S)| with alpha=m(S)/m(R). A 4D treatment plan on a ten
      phase 4D-CT lung patient is used to demonstrate the dose mapping error
      evaluations for a patient case, in which the accumulated dose, D(R)=?(S=0) (9)d(S
      >R), and associated error values (DeltaD(m) and DeltaD(d)) are calculated for a
      uniformly spaced set of ROIs. RESULTS: For the single sample patient dose
      distribution, the average accumulated differential dose mapping error is 4.3%,
      the average absolute differential dose mapping error is 10.8%, and the average
      accumulated mean dose mapping error is 5.0%. Accumulated differential dose
      mapping errors within the gross tumor volume (GTV) and planning target volume
      (PTV) are lower, 0.73% and 2.33%, respectively. CONCLUSIONS: A method has been
      presented to evaluate the dose mapping error introduced by the dose mapping
      process. This method has been applied to evaluate the 4D dose calculation process
      implemented in a commercial treatment planning system. The method could
      potentially be developed as a fully-automatic QA method in image guided adaptive
      radiation therapy (IGART).

PMID- 22482634
TI  - Organ doses for reference pediatric and adolescent patients undergoing computed
      tomography estimated by Monte Carlo simulation.
AB  - PURPOSE: To establish an organ dose database for pediatric and adolescent
      reference individuals undergoing computed tomography (CT) examinations by using
      Monte Carlo simulation. The data will permit rapid estimates of organ and
      effective doses for patients of different age, gender, examination type, and CT
      scanner model. METHODS: The Monte Carlo simulation model of a Siemens Sensation
      16 CT scanner previously published was employed as a base CT scanner model. A set
      of absorbed doses for 33 organs/tissues normalized to the product of 100 mAs and
      CTDI(vol) (mGy/100 mAs mGy) was established by coupling the CT scanner model with
      age-dependent reference pediatric hybrid phantoms. A series of single axial scans
      from the top of head to the feet of the phantoms was performed at a slice
      thickness of 10 mm, and at tube potentials of 80, 100, and 120 kVp. Using the
      established CTDI(vol)- and 100 mAs-normalized dose matrix, organ doses for
      different pediatric phantoms undergoing head, chest, abdomen-pelvis, and chest
      abdomen-pelvis (CAP) scans with the Siemens Sensation 16 scanner were estimated
      and analyzed. The results were then compared with the values obtained from three
      independent published methods: CT-Expo software, organ dose for abdominal CT scan
      derived empirically from patient abdominal circumference, and effective dose per
      dose-length product (DLP). RESULTS: Organ and effective doses were calculated and
      normalized to 100 mAs and CTDI(vol) for different CT examinations. At the same
      technical setting, dose to the organs, which were entirely included in the CT
      beam coverage, were higher by from 40 to 80% for newborn phantoms compared to
      those of 15-year phantoms. An increase of tube potential from 80 to 120 kVp
      resulted in 2.5-2.9-fold greater brain dose for head scans. The results from this
      study were compared with three different published studies and/or techniques.
      First, organ doses were compared to those given by CT-Expo which revealed dose
      differences up to several-fold when organs were partially included in the scan
      coverage. Second, selected organ doses from our calculations agreed to within 20%
      of values derived from empirical formulae based upon measured patient abdominal
      circumference. Third, the existing DLP-to-effective dose conversion coefficients
      tended to be smaller than values given in the present study for all examinations
      except head scans. CONCLUSIONS: A comprehensive organ/effective dose database was
      established to readily calculate doses for given patients undergoing different CT
      examinations. The comparisons of our results with the existing studies highlight
      that use of hybrid phantoms with realistic anatomy is important to improve the
      accuracy of CT organ dosimetry. The comprehensive pediatric dose data developed
      here are the first organ-specific pediatric CT scan database based on the
      realistic pediatric hybrid phantoms which are compliant with the reference data
      from the International Commission on Radiological Protection (ICRP). The organ
      dose database is being coupled with an adult organ dose database recently
      published as part of the development of a user-friendly computer program enabling
      rapid estimates of organ and effective dose doses for patients of any age,
      gender, examination types, and CT scanner model.

PMID- 22482635
TI  - Enhanced dosimetry procedures and assessment for EBT2 radiochromic film.
AB  - PURPOSE: Quantitatively determine an optimum image analysis procedure to mitigate
      inhomogeneities within the EBT2 film and from scanning for accurate absolute dose
      measurement deposited by an external radiation therapy beam. Multichannel
      dosimetry procedures were conceived, described, and quantitatively tested against
      single and dual channel dosimetry. METHODS: A solid water(TM) block was placed on
      CT imaging and treatment tables in a configuration that avoids bulky compressive
      devices. CT markers helped register the CT to the treatment plan and the
      radiation dose distribution from the radiochromic film. The CT images were
      digitally rotated and resampled to match the spatial resolution of the scanned
      dosimetric distribution and treatment plan. The ECLIPSE treatment plan planes
      were digitally translated through digital triangulation of the treatment
      isocenter to the CT markers in the CT image. A 6 MV photon beam, conforming to
      the treatment plan, irradiated the EBT2 film sandwiched between solid water(TM)
      slabs. The exposed radiochromic film images were rotated and translated to the CT
      images using coincident markers in the CT image that are associated with
      "tattoos" marked on the radiochromic film. The exposed radiochromic film gray
      levels from a flatbed scanner in reflection mode were converted to dose using
      calibration films. The test dose distribution was scanned and averaged six times
      to reduce temporal noise. This study generated dose distributions using the red
      channel alone, green channel alone, ratio of the red to blue channel, ratio of
      the green to blue channel, a hybrid approach combining the green to blue ratio
      for higher doses (>80 cGy) with the red to blue ratio (<80 cGy), multichannel
      averaging and optimized autonomous multichannel correction. Single channel,
      multichannel, and channel ratio methods for processing the exposed radiochromic
      film were compared to the treatment plan via gamma analysis. The ellipsoidal
      decision surface was defined by its axes of 3% of the maximum dose and 3 mm in
      the horizontal and vertical directions. RESULTS: The multichannel dosimetry
      procedures provided excellent agreement with calculation of the dose distribution
      as determined by the gamma analysis. The green channel mostly performed as well
      or better than the red channel. The green to blue channel ratio for doses when
      combined with red to blue ratio ("Hybrid") achieved a high level performance. In
      addition, new registration procedures were developed and tested for aiding the
      comparison of calculated and experimentally determined dose distributions.
      CONCLUSIONS: This study described, developed, and tested new processing methods
      for reducing inaccuracies in absolute dose determination due to inhomogeneities
      within the film and from scanning. This study found better performance using
      optimized multichannel following averaging of all color channels. Combining the
      channel ratios in a hybrid approach also achieved high performance. Averaging the
      test films reduced temporal noise that severely degraded the blue channel. This
      methodology avoided using cumbersome, registered correction matrices. Novel
      registration and digital rotation of CT images enabled quantitative testing and
      helped improve contact between the radiochromic film and phantom.

PMID- 22482636
TI  - Quantifying the gantry sag on linear accelerators and introducing an MLC-based
      compensation strategy.
AB  - PURPOSE: Gantry sag is one of the well-known sources of mechanical imperfections
      that compromise the spatial accuracy of radiation dose delivery. The objectives
      of this study were to quantify the gantry sag on multiple linear accelerators
      (linacs), to investigate a multileaf collimator (MLC)-based strategy to
      compensate for gantry sag, and to verify the gantry sag and its compensation with
      film measurements. METHODS: The authors used the Winston-Lutz method to measure
      gantry sag on three Varian linacs. A ball bearing phantom was imaged with
      megavolt radiation fields at 10 degrees  gantry angle intervals. The images
      recorded with an electronic portal imaging device were analyzed to derive the
      radiation isocenter and the gantry sag, that is, the superior-inferior wobble of
      the radiation field center, as a function of the gantry angle. The authors then
      attempted to compensate for the gantry sag by applying a gantry angle-specific
      correction to the MLC leaf positions. The gantry sag and its compensation were
      independently verified using film measurements. RESULTS: Gantry sag was
      reproducible over a six-month measurement period. The maximum gantry sag was
      found to vary from 0.7 to 1.0 mm, depending on the linac and the collimator
      angle. The radiation field center moved inferiorly (i.e., away from the gantry)
      when the gantry was rotated from 0 degrees  to 180 degrees . After the MLC leaf
      position compensation was applied at 90 degrees  collimator angle, the maximum
      gantry sag was reduced to <0.2 mm. The film measurements at gantry angles of 0
      degrees  and 180 degrees  verified the inferior shift of the radiation fields and
      the effectiveness of MLC compensation. CONCLUSIONS: The results indicate that
      gantry sag on a linac can be quantitatively measured using a simple phantom and
      an electronic portal imaging device. Reduction of gantry sag is feasible by
      applying a gantry angle-specific correction to MLC leaf positions at 90 degrees 
      collimator angle.

PMID- 22482637
TI  - Feasibility of low-dose single-view 3D fiducial tracking concurrent with external
      beam delivery.
AB  - PURPOSE: In external-beam radiation therapy, existing on-board x-ray imaging
      chains orthogonal to the delivery beam cannot recover 3D target trajectories from
      a single view in real-time. This limits their utility for real-time motion
      management concurrent with beam delivery. To address this limitation, the authors
      propose a novel concept for on-board imaging based on the inverse-geometry
      Scanning-Beam Digital X-ray (SBDX) system and evaluate its feasibility for single
      view 3D intradelivery fiducial tracking. METHODS: A chest phantom comprising a
      posterior wall, a central lung volume, and an anterior wall was constructed. Two
      fiducials were placed along the mediastinal ridge between the lung cavities: a
      1.5 mm diameter steel sphere superiorly and a gold cylinder (2.6 mm length * 0.9
      mm diameter) inferiorly. The phantom was placed on a linear motion stage that
      moved sinusoidally. Fiducial motion was along the source-detector (z) axis of the
      SBDX system with +/-10 mm amplitude and a programmed period of either 3.5 s or 5
      s. The SBDX system was operated at 15 frames per second, 100 kVp, providing good
      apparent conspicuity of the fiducials. With the stage moving, detector data were
      acquired and subsequently reconstructed into 15 planes with a 12 mm plane-to
      plane spacing using digital tomosynthesis. A tracking algorithm was applied to
      the image planes for each temporal frame to determine the position of each
      fiducial in (x,y,z)-space versus time. A 3D time-sinusoidal motion model was fit
      to the measured 3D coordinates and root mean square (RMS) deviations about the
      fitted trajectory were calculated. RESULTS: Tracked motion was sinusoidal and
      primarily along the source-detector (z) axis. The RMS deviation of the tracked z
      coordinate ranged from 0.53 to 0.71 mm. The motion amplitude derived from the
      model fit agreed with the programmed amplitude to within 0.28 mm for the steel
      sphere and within -0.77 mm for the gold seed. The model fit periods agreed with
      the programmed periods to within 7%. CONCLUSIONS: Three dimensional fiducial
      tracking with approximately 1 mm or better accuracy and precision appears to be
      feasible with SBDX, supporting its use to guide radiotherapy.

PMID- 22482638
TI  - A filtered backprojection MAP algorithm with nonuniform sampling and noise
      modeling.
AB  - PURPOSE: The goal of this paper is to extend our recently developed FBP (filtered
      backprojection) algorithm, which has the same characteristics of an iterative
      Landweber algorithm, to an FBP algorithm with the same characteristics of an
      iterative MAP (maximum a posteriori) algorithm. The newly developed FBP algorithm
      also works when the angular sampling interval is not uniform. The projection
      noise variance can be modeled using a view-based weighting scheme. METHODS: The
      new objective function contains projection noise model dependent weighting
      factors and image dependent prior (i.e., a Bayesian term). The noise weighting is
      view-by-view based. For the first time, the FBP algorithm is able to model the
      projection noise. Based on the formulation of the iterative Landweber MAP
      algorithm, a frequency-domain window function is derived for each iteration of
      the Landweber MAP algorithm. As a result, the ramp filter and the windowing
      function are both modified by the Bayesian component. This new FBP algorithm can
      be applied to a projection data set that is not uniformly sampled. RESULTS:
      Computer simulations show that the new FBP-MAP algorithm with window function
      index k and the iterative Landweber MAP algorithm with iteration number k give
      similar reconstructions in terms of resolution and noise texture. An example of
      transmission x-ray CT shows that the noise modeling method is able to
      significantly reduce the streaking artifacts associated with low-dose CT.
      CONCLUSIONS: View-based noise weighting scheme can be introduced to the FBP
      algorithm as a weighting factor in the window function. The new FBP algorithm is
      able to provide similar results to the iterative MAP algorithm if the ramp filter
      is modified with a additive term. Nonuniform sampling and sensitivity can be
      accommodated by proper backprojection weighting.

PMID- 22482639
TI  - Spectral analysis of near-infrared spectroscopy signals measured from prefrontal
      lobe in subjects at risk for stroke.
AB  - PURPOSE: The objective of this study was to assess the spontaneous cerebral
      oscillations based on the wavelet transform of near-infrared spectroscopy (NIRS)
      signals in subjects at risk for atherosclerotic stroke. METHODS: A total of 32
      subjects were recruited from the university to participate in this study: 20 were
      normal subjects (age = 59.6 +/- 10.2 year) and the other 12 were subjects at risk
      for ischemic stroke (age = 60.2 +/- 10.1 year).The cerebral oxygenation signal
      was monitored for 10 min from the left prefrontal lobe using NIRS. RESULTS: With
      spectral analysis based on wavelet transform, five frequency intervals were
      identified (I, 0.005-0.02 Hz; II, 0.02-0.06 Hz; III, 0.06-0.15 Hz; IV, 0.15-0.40
      Hz; and V, 0.40-2.0 Hz). The amplitude of the [Hb] in the frequency intervals
      from I to V and of the [HbO(2)] in frequency intervals I and V in subjects at
      risk for stroke were found to be significantly lower compared to the amplitudes
      in normal subjects. CONCLUSIONS: The reduction of spontaneous oscillations in
      these subjects suggests an increased stiffness in the cerebral artery. This
      indicates the possibility of applying spontaneous oscillations, based on the
      wavelet transform of NIRS signals, to assess the risk in subjects with
      atherosclerosis.

PMID- 22482640
TI  - A stochastic approach to estimate the uncertainty of dose mapping caused by
      uncertainties in b-spline registration.
AB  - PURPOSE: In fractionated radiation therapy, image guidance with daily tomographic
      imaging becomes more and more clinical routine. In principle, this allows for
      daily computation of the delivered dose and for accumulation of these daily dose
      distributions to determine the actually delivered total dose to the patient.
      However, uncertainties in the mapping of the images can translate into errors of
      the accumulated total dose, depending on the dose gradient. In this work, an
      approach to estimate the uncertainty of mapping between medical images is
      proposed that identifies areas bearing a significant risk of inaccurate dose
      accumulation. METHODS: This method accounts for the geometric uncertainty of
      image registration and the heterogeneity of the dose distribution, which is to be
      mapped. Its performance is demonstrated in context of dose mapping based on b
      spline registration. It is based on evaluation of the sensitivity of dose mapping
      to variations of the b-spline coefficients combined with evaluation of the
      sensitivity of the registration metric with respect to the variations of the
      coefficients. It was evaluated based on patient data that was deformed based on a
      breathing model, where the ground truth of the deformation, and hence the actual
      true dose mapping error, is known. RESULTS: The proposed approach has the
      potential to distinguish areas of the image where dose mapping is likely to be
      accurate from other areas of the same image, where a larger uncertainty must be
      expected. CONCLUSIONS: An approach to identify areas where dose mapping is likely
      to be inaccurate was developed and implemented. This method was tested for dose
      mapping, but it may be applied in context of other mapping tasks as well.

PMID- 22482641
TI  - Experimental validation of deterministic Acuros XB algorithm for IMRT and VMAT
      dose calculations with the Radiological Physics Center's head and neck phantom.
AB  - PURPOSE: The purpose of this study was to verify the dosimetric performance of
      Acuros XB (AXB), a grid-based Boltzmann solver, in intensity-modulated radiation
      therapy (IMRT) and volumetric-modulated arc therapy (VMAT). METHODS: The
      Radiological Physics Center (RPC) head and neck (H&N) phantom was used for all
      calculations and measurements in this study. Clinically equivalent IMRT and VMAT
      plans were created on the RPC H&N phantom in the Eclipse treatment planning
      system (version 10.0) by using RPC dose prescription specifications. The dose
      distributions were calculated with two different algorithms, AXB 11.0.03 and
      anisotropic analytical algorithm (AAA) 10.0.24. Two dose report modes of AXB were
      recorded: dose-to-medium in medium (D(m,m)) and dose-to-water in medium (D(w,m)).
      Each treatment plan was delivered to the RPC phantom three times for
      reproducibility by using a Varian Clinac iX linear accelerator. Absolute point
      dose and planar dose were measured with thermoluminescent dosimeters (TLDs) and
      GafChromic(r) EBT2 film, respectively. Profile comparison and 2D gamma analysis
      were used to quantify the agreement between the film measurements and the
      calculated dose distributions from both AXB and AAA. The computation times for
      AAA and AXB were also evaluated. RESULTS: Good agreement was observed between
      measured doses and those calculated with AAA or AXB. Both AAA and AXB calculated
      doses within 5% of TLD measurements in both the IMRT and VMAT plans. Results of
      AXB_D(m,m) (0.1% to 3.6%) were slightly better than AAA (0.2% to 4.6%) or
      AXB_D(w,m) (0.3% to 5.1%). The gamma analysis for both AAA and AXB met the RPC
      7%/4 mm criteria (over 90% passed), whereas AXB_D(m,m) met 5%/3 mm criteria in
      most cases. AAA was 2 to 3 times faster than AXB for IMRT, whereas AXB was 4-6
      times faster than AAA for VMAT. CONCLUSIONS: AXB was found to be satisfactorily
      accurate when compared to measurements in the RPC H&N phantom. Compared with AAA,
      AXB results were equal to or better than those obtained with film measurements
      for IMRT and VMAT plans. The AXB_D(m,m) reporting mode was found to be closer to
      TLD and film measurements than was the AXB_D(w,m) mode. AXB calculation time was
      found to be significantly shorter (* 4) than AAA for VMAT.

PMID- 22482642
TI  - A novel methodology for 3D deformable dosimetry.
AB  - PURPOSE: Interfraction and intrafraction variation in anatomic structures is a
      significant challenge in contemporary radiotherapy. The objective of this work is
      to develop a novel tool for deformable structure dosimetry, using a tissue
      equivalent deformable gel dosimeter that can reproducibly simulate targets
      subject to deformation. This will enable direct measurement of integrated doses
      delivered in different deformation states, and the verification of dose deforming
      algorithms. METHODS: A modified version of the nPAG polymer gel has been used as
      a deformable 3D dosimeter and phantom to investigate doses delivered to deforming
      tissue-equivalent geometry. The deformable gel (DEFGEL) dosimeter/phantom is
      comprised of polymer gel in a latex membrane, moulded (in this case) into a
      cylindrical geometry, and deformed with an acrylic compressor. Fifteen aluminium
      fiducial markers (FM) were implanted into DEFGEL phantoms and the reproducibility
      of deformation was determined via multiple computed tomography (CT) scans in
      deformed and nondeformed states before and after multiple (up to 150)
      deformations. Dose was delivered to the DEFGEL phantom in three arrangements: (i)
      without deformation, (ii) with deformation, and (iii) cumulative exposures with
      and without deformation, i.e., dose integration. Irradiations included both
      square field and a stereotactic multiple dynamic arc treatment adapted from a
      patient plan. Doses delivered to the DEFGEL phantom were read out using cone beam
      optical CT. RESULTS: Reproducibility was verified by observation of interscan
      shifts of FM locations (as determined via CT), measured from an absolute
      reference point and in terms of inter-FM distance. The majority (76%) of points
      exhibited zero shift, with others shifting by one pixel size consistent with
      setup error as confirmed with a control sample. Comparison of dose profiles and
      2D isodose distributions from the three arrangements illustrated complex spatial
      redistribution of dose in all three dimensions occurring as a result of the
      change in shape of the target between irradiations, even for a relatively simple
      deformation. Discrepancies of up to 30% of the maximum dose were evident from
      dose difference maps for three orthogonal planes taken through the isocenter of a
      stereotactic field. CONCLUSIONS: This paper describes the first use of a tissue
      equivalent, 3D dose-integrating deformable phantom that yields integrated or
      redistributed dosimetric information. The proposed methodology readily yields
      three-dimensional (3D) dosimetric data from radiation delivery to the DEFGEL
      phantom in deformed and undeformed states. The impacts of deformation on dose
      distributions were readily seen in the isodose contours and line profiles from
      the three arrangements. It is demonstrated that the system is potentially capable
      of reproducibly emulating the physical deformation of an organ, and therefore can
      be used to evaluate absorbed doses to deformable targets and organs at risk in
      three dimensions and to validate deformation algorithms applied to dose
      distributions.

PMID- 22482643
TI  - Concurrent segmentation of the prostate on MRI and CT via linked statistical
      shape models for radiotherapy planning.
AB  - PURPOSE: Prostate gland segmentation is a critical step in prostate radiotherapy
      planning, where dose plans are typically formulated on CT. Pretreatment MRI is
      now beginning to be acquired at several medical centers. Delineation of the
      prostate on MRI is acknowledged as being significantly simpler to perform,
      compared to delineation on CT. In this work, the authors present a novel
      framework for building a linked statistical shape model (LSSM), a statistical
      shape model (SSM) that links the shape variation of a structure of interest (SOI)
      across multiple imaging modalities. This framework is particularly relevant in
      scenarios where accurate boundary delineations of the SOI on one of the
      modalities may not be readily available, or difficult to obtain, for training a
      SSM. In this work the authors apply the LSSM in the context of multimodal
      prostate segmentation for radiotherapy planning, where the prostate is
      concurrently segmented on MRI and CT. METHODS: The framework comprises a number
      of logically connected steps. The first step utilizes multimodal registration of
      MRI and CT to map 2D boundary delineations of the prostate from MRI onto
      corresponding CT images, for a set of training studies. Hence, the scheme
      obviates the need for expert delineations of the gland on CT for explicitly
      constructing a SSM for prostate segmentation on CT. The delineations of the
      prostate gland on MRI and CT allows for 3D reconstruction of the prostate shape
      which facilitates the building of the LSSM. In order to perform concurrent
      prostate MRI and CT segmentation using the LSSM, the authors employ a region
      based level set approach where the authors deform the evolving prostate boundary
      to simultaneously fit to MRI and CT images in which voxels are classified to be
      either part of the prostate or outside the prostate. The classification is
      facilitated by using a combination of MRI-CT probabilistic spatial atlases and a
      random forest classifier, driven by gradient and Haar features. RESULTS: The
      authors acquire a total of 20 MRI-CT patient studies and use the leave-one-out
      strategy to train and evaluate four different LSSMs. First, a fusion-based LSSM
      (fLSSM) is built using expert ground truth delineations of the prostate on MRI
      alone, where the ground truth for the gland on CT is obtained via coregistration
      of the corresponding MRI and CT slices. The authors compare the fLSSM against
      another LSSM (xLSSM), where expert delineations of the gland on both MRI and CT
      are employed in the model building; xLSSM representing the idealized LSSM. The
      authors also compare the fLSSM against an exclusive CT-based SSM (ctSSM), built
      from expert delineations of the gland on CT alone. In addition, two LSSMs trained
      using trainee delineations (tLSSM) on CT are compared with the fLSSM. The results
      indicate that the xLSSM, tLSSMs, and the fLSSM perform equivalently, all of them
      out-performing the ctSSM. CONCLUSIONS: The fLSSM provides an accurate alternative
      to SSMs that require careful expert delineations of the SOI that may be difficult
      or laborious to obtain. Additionally, the fLSSM has the added benefit of
      providing concurrent segmentations of the SOI on multiple imaging modalities.

PMID- 22482644
TI  - Nanoscale imaging of the bone cell network with synchrotron X-ray tomography:
      optimization of acquisition setup.
AB  - PURPOSE: The fundamental role of the osteocyte cell network in regulating the
      bone remodeling has become evident in the last years. This has raised the
      necessity to explore this complex three-dimensional interconnected structure, but
      the existing investigation methods cannot provide an adequate assessment. The
      authors propose to use parallel beam synchrotron radiation computed tomography at
      the nanoscale to image in three dimensions the osteocyte lacunocanalicular
      network. To this aim, the authors study the feasibility of this technique and
      present an optimized imaging protocol suited for the bone cell network. Moreover,
      they demonstrate the multifaceted information provided by this method. METHODS:
      The high brilliance of synchrotron radiation combined with state of art detectors
      permits reaching nanoscale spatial resolution. With a nominal pixel size of 280
      nm, the parallel beam computed tomography setup at the ID19 experimental station
      of the ESRF is capable of imaging the bone lacunocanalicular network, considering
      that the reported diameter of canaliculi is in the range 300-600 nm. However, the
      actual resolution is limited by the detector and by the radiation dose causing
      sample damage during the scan. The authors sought to overcome these limitations
      by optimizing the imaging setup and the acquisition parameters in order to
      minimize the necessary radiation dose to create the images and to improve the
      spatial resolution of the detector. RESULTS: The authors achieved imaging of the
      osteocyte cell network in human bone. Due to the optimization of the imaging
      setup and acquisition parameters, they obtained simultaneously a radiation dose
      reduction and an increase of the signal to noise ratio in the images. This
      permitted the authors to generate the first three-dimensional images of the
      lacunocanalicular network in an area covering several osteons, the fundamental
      functional units in the bone cortex. The method enables assessment of both
      architectural parameters of the microporosity and of mineralization degree in the
      bone matrix. The authors found that the cell network is dense and connected
      inside osteonal tissue. Conversely, the cell lacunae are sparse, unorganized, and
      disconnected in interstitial tissue. CONCLUSIONS: The authors show that
      synchrotron radiation computed tomography is a feasible technique to assess the
      lacunocanalicular network in three dimensions. This is possible due to an optimal
      imaging setup in which the detector plays an important role. The authors could
      establish two valid setups, based on two different insertion devices. These
      results give access to new information on the bone cell network architecture,
      covering a number of cells two orders of magnitude greater than existing
      techniques. This enables biomedical studies on series of samples, paving the way
      to better understanding of bone fragility and to new treatments for bone
      diseases.

PMID- 22482645
TI  - A simplified technique for delivering total body irradiation (TBI) with improved
      dose homogeneity.
AB  - PURPOSE: Total body irradiation (TBI) with megavoltage photon beams has been
      accepted as an important component of management for a number of hematologic
      malignancies, generally as part of bone marrow conditioning regimens. The purpose
      of this paper is to present and discuss the authors' TBI technique, which both
      simplifies the treatment process and improves the treatment quality. METHODS: An
      AP/PA TBI treatment technique to produce uniform dose distributions using
      sequential collimator reductions during each fraction was implemented, and a
      sample calculation worksheet is presented. Using this methodology, the dosimetric
      characteristics of both 6 and 18 MV photon beams, including lung dose under
      cerrobend blocks was investigated. A method of estimating midplane lung doses
      based on measured entrance and exit doses was proposed, and the estimated results
      were compared with measurements. RESULTS: Whole body midplane dose uniformity of
      +/-10% was achieved with no more than two collimator-based beam modulations. The
      proposed model predicted midplane lung doses 5% to 10% higher than the measured
      doses for 6 and 18 MV beams. The estimated total midplane doses were within +/-5%
      of the prescribed midplane dose on average except for the lungs where the doses
      were 6% to 10% lower than the prescribed dose on average. CONCLUSIONS: The
      proposed TBI technique can achieve dose uniformity within +/-10%. This technique
      is easy to implement and does not require complicated dosimetry and/or
      compensators.

PMID- 22482646
TI  - Time-delayed summation as a means of improving resolution on fast rotating
      computed tomography systems.
AB  - PURPOSE: Modern computed tomography (CT) systems are supporting increasingly fast
      rotation speeds, which are a prerequisite for fast dynamic acquisition, e.g. in
      perfusion imaging, and for new modalities such as dedicated breast CT, where
      breathhold scanning is indicated. However, not all detector technologies are
      supporting the high frame rates that are necessary to retain high resolution for
      objects far away from the isocenter. Even on systems that would support a
      sufficiently high frame rate, the necessary bandwidth of the data transfer from
      the rotating gantry stills remains challenging. The authors evaluated a pixel
      shifting technique termed time-delayed summation (TDS) as a method of increasing
      resolution on fast rotating CT systems without the need to increase the frame
      rate. METHODS: In TDS mode, detector pixel values are shifted along rows during
      image acquisition to compensate for detector motion. In order to fully exploit
      TDS, focal spot position control (FSC) was used in combination with TDS. FSC
      applies a counter movement to the x-ray focal spot during image acquisition such
      that it is kept fixed in space. As a proof of concept, measurements were
      performed on a prototype photon counting detector capable of TDS. The detector
      was mounted on a movable table and a gold wire phantom was imaged with different
      TDS settings and detector velocities. Additionally, simulations of a broad range
      of TDS and FSC settings on two different modalities, a clinical CT scanner and a
      breast CT scanner, and two different detector geometries, flat and cylindrical,
      were performed to assess the gain in resolution and contrast in cylindrical water
      phantoms containing a small wire at distances from the phantom center varied from
      5% to 90% of the phantom radius. As figures of merit, the modulation transfer
      function (MTF) at 10% and the maximum contrast were used and compared against the
      respective values when using step-and-shoot acquisition, which means stopping the
      rotation when a projection image is acquired. RESULTS: Measurements showed that
      detector movement and the resulting blurring of the wire projections were
      compensated to the expected degree when using the appropriate number of TDS
      shifts per frame (TDS factor). Using simulations it was found that when using the
      optimal TDS factor, over 90% of the resolution achieved in step-and-shot mode was
      reached for all investigated wire positions. TDS showed better performance on a
      cylindrical detector that on the same system with a flat detector. TDS factors
      that were deviating from the optimum by more than 1 shift led to a performance
      below that of standard continuous acquisition. CONCLUSIONS: The findings of this
      study encourage the combined usage of TDS and FSC in systems that require fast
      rotation. The integration of TDS in state-of-the-art x-ray detectors is feasible.

PMID- 22482647
TI  - The use of a multiobjective evolutionary algorithm to increase flexibility in the
      search for better IMRT plans.
AB  - PURPOSE: To evaluate how a more flexible and thorough multiobjective search of
      feasible IMRT plans affects performance in IMRT optimization. METHODS: A
      multiobjective evolutionary algorithm (MOEA) was used as a tool to investigate
      how expanding the search space to include a wider range of penalty functions
      affects the quality of the set of IMRT plans produced. The MOEA uses a population
      of IMRT plans to generate new IMRT plans through deterministic minimization of
      recombined penalty functions that are weighted sums of multiple, tissue-specific
      objective functions. The quality of the generated plans are judged by an
      independent set of nonconvex, clinically relevant decision criteria, and all
      dominated plans are eliminated. As this process repeats itself, better plans are
      produced so that the population of IMRT plans will approach the Pareto front.
      Three different approaches were used to explore the effects of expanding the
      search space. First, the evolutionary algorithm used genetic optimization
      principles to search by simultaneously optimizing both the weights and tissue
      specific dose parameters in penalty functions. Second, penalty function
      parameters were individually optimized for each voxel in all organs at risk
      (OARs) in the MOEA. Finally, a heuristic voxel-specific improvement (VSI)
      algorithm that can be used on any IMRT plan was developed that incrementally
      improves voxel-specific penalty function parameters for all structures (OARs and
      targets). Different approaches were compared using the concept of domination
      comparison applied to the sets of plans obtained by multiobjective optimization.
      RESULTS: MOEA optimizations that simultaneously searched both importance weights
      and dose parameters generated sets of IMRT plans that were superior to sets of
      plans produced when either type of parameter was fixed for four example prostate
      plans. The amount of improvement increased with greater overlap between OARs and
      targets. Allowing the MOEA to search for voxel-specific penalty functions
      improved results for simple cases with three structures but did not improve
      results for a more complex case with seven structures. For this modification, the
      amount of improvement increased with less overlap between OARs and targets. The
      voxel-specific improvement algorithm improved results for all cases, and its
      clinical relevance was demonstrated in a complex prostate and a very complex head
      and neck case. CONCLUSIONS: Using an evolutionary algorithm as a tool, it was
      found that allowing more flexibility in the search space enhanced performance.
      The two strategies of (a) varying the weights and reference doses in the
      objective function and (b) removing the constraint of equal penalties for all
      voxels in a structure both generated sets of plans that dominated sets of plans
      considered to be "Pareto optimal" within the conventional, more limited search
      space. When considering voxel-specific objectives, the very large search space
      can lead to convergence problems in the MOEA for complex cases, but this is not
      an issue for the VSI algorithm.

PMID- 22482648
TI  - Comparative analysis of nonlinear dimensionality reduction techniques for breast
      MRI segmentation.
AB  - PURPOSE: Visualization of anatomical structures using radiological imaging
      methods is an important tool in medicine to differentiate normal from
      pathological tissue and can generate large amounts of data for a radiologist to
      read. Integrating these large data sets is difficult and time-consuming. A new
      approach uses both supervised and unsupervised advanced machine learning
      techniques to visualize and segment radiological data. This study describes the
      application of a novel hybrid scheme, based on combining wavelet transform and
      nonlinear dimensionality reduction (NLDR) methods, to breast magnetic resonance
      imaging (MRI) data using three well-established NLDR techniques, namely, ISOMAP,
      local linear embedding (LLE), and diffusion maps (DfM), to perform a comparative
      performance analysis. METHODS: Twenty-five breast lesion subjects were scanned
      using a 3T scanner. MRI sequences used were T1-weighted, T2-weighted, diffusion
      weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging. The hybrid
      scheme consisted of two steps: preprocessing and postprocessing of the data. The
      preprocessing step was applied for B(1) inhomogeneity correction, image
      registration, and wavelet-based image compression to match and denoise the data.
      In the postprocessing step, MRI parameters were considered data dimensions and
      the NLDR-based hybrid approach was applied to integrate the MRI parameters into a
      single image, termed the embedded image. This was achieved by mapping all pixel
      intensities from the higher dimension to a lower dimensional (embedded) space.
      For validation, the authors compared the hybrid NLDR with linear methods of
      principal component analysis (PCA) and multidimensional scaling (MDS) using
      synthetic data. For the clinical application, the authors used breast MRI data,
      comparison was performed using the postcontrast DCE MRI image and evaluating the
      congruence of the segmented lesions. RESULTS: The NLDR-based hybrid approach was
      able to define and segment both synthetic and clinical data. In the synthetic
      data, the authors demonstrated the performance of the NLDR method compared with
      conventional linear DR methods. The NLDR approach enabled successful segmentation
      of the structures, whereas, in most cases, PCA and MDS failed. The NLDR approach
      was able to segment different breast tissue types with a high accuracy and the
      embedded image of the breast MRI data demonstrated fuzzy boundaries between the
      different types of breast tissue, i.e., fatty, glandular, and tissue with lesions
      (>86%). CONCLUSIONS: The proposed hybrid NLDR methods were able to segment
      clinical breast data with a high accuracy and construct an embedded image that
      visualized the contribution of different radiological parameters.

PMID- 22482649
TI  - Optimized generation of high resolution breast anthropomorphic software phantoms.
AB  - PURPOSE: The authors present an efficient method for generating anthropomorphic
      software breast phantoms with high spatial resolution. Employing the same region
      growing principles as in their previous algorithm for breast anatomy simulation,
      the present method has been optimized for computational complexity to allow for
      fast generation of the large number of phantoms required in virtual clinical
      trials of breast imaging. METHODS: The new breast anatomy simulation method
      performs a direct calculation of the Cooper's ligaments (i.e., the borders
      between simulated adipose compartments). The calculation corresponds to quadratic
      decision boundaries of a maximum a posteriori classifier. The method is
      multiscale due to the use of octree-based recursive partitioning of the phantom
      volume. The method also provides user-control of the thickness of the simulated
      Cooper's ligaments and skin. RESULTS: Using the proposed method, the authors have
      generated phantoms with voxel size in the range of (25-1000 MUm)(3)/voxel. The
      power regression of the simulation time as a function of the reciprocal voxel
      size yielded a log-log slope of 1.95 (compared to a slope of 4.53 of our previous
      region growing algorithm). CONCLUSIONS: A new algorithm for computer simulation
      of breast anatomy has been proposed that allows for fast generation of high
      resolution anthropomorphic software phantoms.

PMID- 22482650
TI  - Comment on "comparison of secondary neutron dose in proton therapy resulting from
      the use of a tungsten alloy MLC or a brass collimator system" [Med. Phys. 38(11),
      6248-6256 (2011)].

PMID- 22482652
TI  - Reply to "comment on 'correspondence factor for Nucletron surface applicators'".

PMID- 22482653
TI  - Comment on "bridging the gap between IMRT and VMAT: dense angularly sampled and
      sparse intensity modulated radiation therapy" [Med. Phys. 38, 4912-4919 (2011)].

PMID- 22482656
TI  - Reliability of impact forces, hip angles and velocities during simulated forward
      falls using a novel Propelled Upper Limb fall ARrest Impact System (PULARIS).
AB  - Previous forward fall simulation methods have provided good kinematic and kinetic
      data, but are limited in that they have started the falls from a stationary
      position and have primarily simulated uni-directional motion. Therefore, a novel
      Propelled Upper Limb fall ARest Impact System (PULARIS) was designed to address
      these issues during assessments of a variety of fall scenarios. The purpose of
      this study was to present PULARIS and evaluate its ability to impact the upper
      extremities of participants with repeatable velocities, hand forces and hip
      angles in postures and with vertical and horizontal motion consistent with
      forward fall arrest. PULARIS consists of four steel tubing crossbars in a scissor
      like arrangement that ride on metal trolleys within c-channel tracks in the
      ceiling. Participants are suspended beneath PULARIS by the legs and torso in a
      prone position and propelled horizontally via a motor and chain drive until they
      are quick released, and then impact floor-mounted force platforms with both
      hands. PULARIS velocity, hip angles and velocities and impact hand forces of ten
      participants (five male, five female) were collected during three fall types
      (straight-arm, self-selected and bent-arm) and two fall heights (0.05 m and 0.10
      m) to assess the reliability of the impact conditions provided by the system.
      PULARIS and participant hip velocities were found to be quite repeatable (mean
      ICC = 0.81) with small between trial errors (mean = 0.03 m/s). The ratio of
      horizontal to vertical hip velocity components (~0.75) agreed well with
      previously reported data (0.70-0.80). Peak vertical hand impact forces were also
      found to be relatively consistent between trials with a mean ICC of 0.73 and mean
      between trial error of 13.4 N. Up to 83% of the horizontal hand impact forces
      displayed good to excellent reliability (ICC > 0.6) with small between trial
      differences. Finally, the ICCs for between trial hip angles were all classified
      as good to excellent. Overall, PULARIS is a reliable method and is appropriate
      for studying the response of the distal upper extremity to impact loading during
      non-stationary, multi-directional movements indicative of a forward fall. This
      system performed well at different fall heights, and allows for a variety of
      upper and lower extremity, and hip postures to be tested successfully in
      different landing scenarios consistent with elderly and sport-related falls.

PMID- 22482657
TI  - Optimization of cardiovascular stent design using computational fluid dynamics.
AB  - Coronary stent design affects the spatial distribution of wall shear stress
      (WSS), which can influence the progression of endothelialization, neointimal
      hyperplasia, and restenosis. Previous computational fluid dynamics (CFD) studies
      have only examined a small number of possible geometries to identify stent
      designs that reduce alterations in near-wall hemodynamics. Based on a previously
      described framework for optimizing cardiovascular geometries, we developed a
      methodology that couples CFD and three-dimensional shape-optimization for use in
      stent design. The optimization procedure was fully-automated, such that solid
      model construction, anisotropic mesh generation, CFD simulation, and WSS
      quantification did not require user intervention. We applied the method to
      determine the optimal number of circumferentially repeating stent cells (N(C))
      for slotted-tube stents with various diameters and intrastrut areas. Optimal
      stent designs were defined as those minimizing the area of low intrastrut time
      averaged WSS. Interestingly, we determined that the optimal value of N(C) was
      dependent on the intrastrut angle with respect to the primary flow direction.
      Further investigation indicated that stent designs with an intrastrut angle of
      approximately 40 deg minimized the area of low time-averaged WSS regardless of
      vessel size or intrastrut area. Future application of this optimization method to
      commercially available stent designs may lead to stents with superior hemodynamic
      performance and the potential for improved clinical outcomes.

PMID- 22482658
TI  - Perfusion characteristics of the human hepatic microcirculation based on three
      dimensional reconstructions and computational fluid dynamic analysis.
AB  - The perfusion of the liver microcirculation is often analyzed in terms of
      idealized functional units (hexagonal liver lobules) based on a porous medium
      approach. More elaborate research is essential to assess the validity of this
      approach and to provide a more adequate and quantitative characterization of the
      liver microcirculation. To this end, we modeled the perfusion of the liver
      microcirculation using an image-based three-dimensional (3D) reconstruction of
      human liver sinusoids and computational fluid dynamics techniques. After vascular
      corrosion casting, a microvascular sample (+/-0.134 mm(3)) representing three
      liver lobules, was dissected from a human liver vascular replica and scanned
      using a high resolution (2.6 MUm) micro-CT scanner. Following image processing, a
      cube (0.15 * 0.15 * 0.15 mm(3)) representing a sample of intertwined and
      interconnected sinusoids, was isolated from the 3D reconstructed dataset to
      define the fluid domain. Three models were studied to simulate flow along three
      orthogonal directions (i.e., parallel to the central vein and in the radial and
      circumferential directions of the lobule). Inflow and outflow guidances were
      added to facilitate solution convergence, and good quality volume meshes were
      obtained using approximately 9 * 10(6) tetrahedral cells. Subsequently, three
      computational fluid dynamics models were generated and solved assuming Newtonian
      liquid properties (viscosity 3.5 mPa s). Post-processing allowed to visualize and
      quantify the microvascular flow characteristics, to calculate the permeability
      tensor and corresponding principal permeability axes, as well as the 3D porosity.
      The computational fluid dynamics simulations provided data on pressure
      differences, preferential flow pathways and wall shear stresses. Notably, the
      pressure difference resulting from the flow simulation parallel to the central
      vein (0-100 Pa) was clearly smaller than the difference from the radial (0-170
      Pa) and circumferential (0-180 Pa) flow directions. This resulted in a higher
      permeability along the central vein direction (k(d,33) = 3.64 * 10(-14) m(2)) in
      comparison with the radial (k(d,11) = 1.56 * 10(-14) m(2)) and circumferential
      (k(d,22) = 1.75 * 10(-14) m(2)) permeabilities which were approximately equal.
      The mean 3D porosity was 14.3. Our data indicate that the human hepatic
      microcirculation is characterized by a higher permeability along the central vein
      direction, and an about two times lower permeability along the radial and
      circumferential directions of a lobule. Since the permeability coefficients
      depend on the flow direction, (porous medium) liver microcirculation models
      should take into account sinusoidal anisotropy.

PMID- 22482659
TI  - Mechanical behavior of collagen-fibrin co-gels reflects transition from series to
      parallel interactions with increasing collagen content.
AB  - Fibrin and collagen, biopolymers occurring naturally in the body, are
      biomaterials commonly-used as scaffolds for tissue engineering. How collagen and
      fibrin interact to confer macroscopic mechanical properties in collagen-fibrin
      composite systems remains poorly understood. In this study, we formulated
      collagen-fibrin co-gels at different collagen-to-fibrin ratios to observe changes
      in the overall mechanical behavior and microstructure. A modeling framework of a
      two-network system was developed by modifying our micro-scale model, considering
      two forms of interaction between the networks: (a) two interpenetrating but
      noninteracting networks ("parallel"), and (b) a single network consisting of
      randomly alternating collagen and fibrin fibrils ("series"). Mechanical testing
      of our gels show that collagen-fibrin co-gels exhibit intermediate properties
      (UTS, strain at failure, tangent modulus) compared to those of pure collagen and
      fibrin. The comparison with model predictions show that the parallel and series
      model cases provide upper and lower bounds, respectively, for the experimental
      data, suggesting that a combination of such interactions exists between the
      collagen and fibrin in co-gels. A transition from the series model to the
      parallel model occurs with increasing collagen content, with the series model
      best describing predominantly fibrin co-gels, and the parallel model best
      describing predominantly collagen co-gels.

PMID- 22482660
TI  - FEBio: finite elements for biomechanics.
AB  - In the field of computational biomechanics, investigators have primarily used
      commercial software that is neither geared toward biological applications nor
      sufficiently flexible to follow the latest developments in the field. This lack
      of a tailored software environment has hampered research progress, as well as
      dissemination of models and results. To address these issues, we developed the
      FEBio software suite (http://mrl.sci.utah.edu/software/febio), a nonlinear
      implicit finite element (FE) framework, designed specifically for analysis in
      computational solid biomechanics. This paper provides an overview of the
      theoretical basis of FEBio and its main features. FEBio offers modeling
      scenarios, constitutive models, and boundary conditions, which are relevant to
      numerous applications in biomechanics. The open-source FEBio software is written
      in C++, with particular attention to scalar and parallel performance on modern
      computer architectures. Software verification is a large part of the development
      and maintenance of FEBio, and to demonstrate the general approach, the
      description and results of several problems from the FEBio Verification Suite are
      presented and compared to analytical solutions or results from other established
      and verified FE codes. An additional simulation is described that illustrates the
      application of FEBio to a research problem in biomechanics. Together with the pre
      and postprocessing software PREVIEW and POSTVIEW, FEBio provides a tailored
      solution for research and development in computational biomechanics.

PMID- 22482661
TI  - Finite element aortic injury reconstruction of near side lateral impacts using
      real world crash data.
AB  - Traumatic rupture of the aorta (TRA) remains the second most common cause of
      death associated with motor vehicle crashes, only less prevalent than brain
      injury. On average, nearly 8000 people die annually in the United States due to
      blunt injury to the aorta. It is observed that over 80% of occupants who suffer
      an aortic injury die at the scene due to exsanguination into the chest cavity. In
      the current study, eight near side lateral impacts, in which TRA occurred, were
      reconstructed using a combination of real world crash data reported in the Crash
      Injury Research and Engineering Network (CIREN) database, finite element (FE)
      models of vehicles, and the Wayne State Human Body Model - II (WSHBM). For the
      eight CIREN cases reconstructed, the high strain regions in the aorta closely
      matched with the autopsy data provided. The peak average maximum principal
      strains in all of the eight CIREN cases were localized in the isthmus region of
      the aorta, distal to the left subclavian artery, and averaged at 22 +/- 6.2%
      while the average maximum pressure in the aorta was found to be 117 +/- 14.7 kPa.

PMID- 22482662
TI  - Experimental evidence of impingement induced strains at the interface and the
      periphery of an embedded acetabular cup implant.
AB  - After total hip arthroplasty, impingement of implant components may occur during
      every-day patient activities causing increased shear stresses at the acetabular
      implant-bone interface. In the literature, impingement related lever-out moments
      were noted for a number of acetabular components. But there is little information
      about pelvic load transfer. The aim of the current study was to measure the three
      dimensional strain distribution at the macrostructured hemispherical interface
      and in the periphery of a standard acetabular press-fit cup in an experimental
      implant-bone substitute model. An experimental setup was developed to simulate
      impingement loading via a lever arm representing the femoral component and the
      lower limb. In one experimental setup 12 strain gauges were embedded at
      predefined positions in the periphery of the acetabular cup implant inside a
      tray, using polyurethane composite resin as a bone substitute material. By
      incremental rotation of the implant tray in steps of 10 and 30 deg, respectively,
      the strains were measured at evenly distributed positions. With the described
      method 288 genuine strain values were measured in the periphery of an embedded
      acetabular cup implant in one experimental setup. In two additional setups the
      strains were evaluated at different distances from the implant interface. Both in
      radial and meridional interface directions strain magnitudes reach their peak
      near the rim of the cup below the impingement site. Values of equatorial strains
      vary near zero and reach their peaks near the rim of the cup on  either side and
      in some distance from the impingement site. Interestingly, the maximum of
      averaged radial strains does not occur, as expected, close to the interface but
      at an interface offset of 5.6 mm. With the described experimental setup it is now
      possible to measure and display the three-dimensional strain distribution in the
      interface and the periphery of an embedded acetabular cup implant. The current
      study provides the first experimental proof of the high local stresses gradients
      in the direct vicinity of the impingement site. The results of the current study
      help for a better understanding of the impingement mechanism and its impact on
      acetabular cup stability.

PMID- 22482663
TI  - Using in vivo Cine and 3D multi-contrast MRI to determine human atherosclerotic
      carotid artery material properties and circumferential shrinkage rate and their
      impact on stress/strain predictions.
AB  - In vivo magnetic resonance image (MRI)-based computational models have been
      introduced to calculate atherosclerotic plaque stress and strain conditions for
      possible rupture predictions. However, patient-specific vessel material
      properties are lacking in those models, which affects the accuracy of their
      stress/strain predictions. A noninvasive approach of combining in vivo Cine MRI,
      multicontrast 3D MRI, and computational modeling was introduced to quantify
      patient-specific carotid artery material properties and the circumferential
      shrinkage rate between vessel in vivo and zero-pressure geometries. In vivo Cine
      and 3D multicontrast MRI carotid plaque data were acquired from 12 patients after
      informed consent. For each patient, one nearly-circular slice and an iterative
      procedure were used to quantify parameter values in the modified Mooney-Rivlin
      model for the vessel and the vessel circumferential shrinkage rate. A sample
      artery slice with and without a lipid core and three material parameter sets
      representing stiff, median, and soft materials from our patient data were used to
      demonstrate the effect of material stiffness and circumferential shrinkage
      process on stress/strain predictions. Parameter values of the Mooney-Rivlin
      models for the 12 patients were quantified. The effective Young's modulus (YM,
      unit: kPa) values varied from 137 (soft), 431 (median), to 1435 (stiff), and
      corresponding circumferential shrinkages were 32%, 12.6%, and 6%, respectively.
      Using the sample slice without the lipid core, the maximum plaque stress values
      (unit: kPa) from the soft and median materials were 153.3 and 96.2, which are
      67.7% and 5% higher than that (91.4) from the stiff material, while the maximum
      plaque strain values from the soft and median materials were 0.71 and 0.293,
      which are about 700% and 230% higher than that (0.089) from the stiff material,
      respectively. Without circumferential shrinkages, the maximum plaque stress
      values (unit: kPa) from the soft, median, and stiff models were inflated to
      330.7, 159.2, and 103.6, which were 116%, 65%, and 13% higher than those from
      models with proper shrinkage. The effective Young's modulus from the 12 human
      carotid arteries studied varied from 137 kPa to 1435 kPa. The vessel
      circumferential shrinkage to the zero-pressure condition varied from 6% to 32%.
      The inclusion of proper shrinkage in models based on in vivo geometry is
      necessary to avoid over-estimating the stresses and strains by up 100%. Material
      stiffness had a greater impact on strain (up to 700%) than on stress (up to 70%)
      predictions. Accurate patient-specific material properties and circumferential
      shrinkage could considerably improve the accuracy of in vivo MRI-based
      computational stress/strain predictions.

PMID- 22482664
TI  - Effect of the intra-abdominal pressure and the center of segmental body mass on
      the lumbar spine mechanics - a computational parametric study.
AB  - Determination of physiological loads in human lumbar spine is critical for
      understanding the mechanisms of lumbar diseases and for designing surgical
      treatments. Computational models have been used widely to estimate the
      physiological loads of the spine during simulated functional activities. However,
      various assumptions on physiological factors such as the intra-abdominal pressure
      (IAP), centers of mass (COMs) of the upper body and lumbar segments, and
      vertebral centers of rotation (CORs) have been made in modeling techniques.
      Systematic knowledge of how these assumptions will affect the predicted spinal
      biomechanics is important for improving the simulation accuracy. In this paper,
      we developed a 3D subject-specific numerical model of the lumbosacral spine
      including T12 and 90 muscles. The effects of the IAP magnitude and COMs locations
      on the COR of each motion segment and on the joint/muscle forces were
      investigated using a global convergence optimization procedure when the subject
      was in a weight bearing standing position. The data indicated that the line
      connecting the CORs showed a smaller curvature than the lordosis of the lumbar
      spine in standing posture when the IAP was 0 kPa and the COMs were 10 mm anterior
      to the geometric center of the T12 vertebra. Increasing the IAP from 0 kPa to 10
      kPa shifted the location of CORs toward the posterior direction (from 1.4 +/- 8.9
      mm anterior to intervertebral disc (IVD) centers to 40.5 +/- 3.1 mm posterior to
      the IVD centers) and reduced the average joint force (from 0.78 +/- 0.11 Body
      weight (BW) to 0.31 +/- 0.07 BW) and overall muscle force (from 349.3 +/- 57.7 N
      to 221.5 +/- 84.2 N). Anterior movement of the COMs from -30 mm to 70 mm relative
      to the geometric center of T12 vertebra caused an anterior shift of the CORs
      (from 25.1 +/- 8.3 mm posterior to IVD centers to 7.8 +/- 6.2 mm anterior to IVD
      centers) and increases of average joint forces (from 0.78 +/- 0.1 BW to 0.93 +/-
      0.1 BW) and muscle force (from 348.9 +/- 47.7 N to 452.9 +/- 58.6 N). Therefore,
      it is important to consider the IAP and correct COMs in order to accurately
      simulate human spine biomechanics. The method and results of this study could be
      useful for designing prevention strategies of spinal injuries and recurrences,
      and for enhancing rehabilitation efficiency.

PMID- 22482665
TI  - Amplitude and phasing of trunk motion is critical for the efficacy of gait
      training aimed at reducing ambulatory loads at the knee.
AB  - The purpose of this study was to determine the contribution of changes in
      amplitude and phasing of medio-lateral trunk sway to a change in the knee
      adduction moment when walking with increased medio-lateral trunk sway. Kinematic
      and kinetic data of walking trials with normal and with increased trunk sway were
      collected for 19 healthy volunteers using a standard motion analysis system. The
      relationship between the change in first peak knee adduction moment (DeltaKAM)
      and change in trunk sway amplitude (DeltaSA; difference between maximum
      contralateral trunk lean and maximum ipsilateral trunk lean) and phasing (SP;
      time of heel-strike relative to time of maximum contralateral and time of maximum
      ipsilateral trunk lean) was determined using nonlinear regression analysis. On
      average, subjects increased their SA by 9.7 +/- 3.6 deg (P < 0.001) with an
      average SP of 98.8 +/- 88.8 ms resulting in an average reduction in the first
      peak knee adduction moment of -55.2 +/- 30.3% (P < 0.001). 64.3% of variability
      in change in peak knee adduction moment with the increased trunk sway condition
      was explained by both differences in SA and SP, and the relationship among these
      parameters was described by the regression equation DeltaKAM = 27.220-4.128
      [middle dot] DeltaSA-64.785 [middle dot] cos(SP). Hence, not only the amplitude
      but also the phasing of trunk motion is critical. Not only lower limb movement
      but also lumbar and thoracic lateral flexion should be considered in the decision
      making process for an optimal intervention aimed at reducing the load on the
      medial compartment of the knee during walking. However, these promising findings
      originated from studies on healthy subjects and their relevance for gait training
      interventions in patients with presumably painful knee osteoarthritis remains to
      be determined.

PMID- 22482666
TI  - The regional contribution of glycosaminoglycans to temporomandibular joint disc
      compressive properties.
AB  - Understanding structure-function relationships in the temporomandibular joint
      (TMJ) disc is a critical first step toward creating functional tissue
      replacements for the large population of patients suffering from TMJ disc
      disorders. While many of these relationships have been identified for the
      collagenous fraction of the disc, this same understanding is lacking for the next
      most abundant extracellular matrix component, sulfated glycosaminoglycans (GAGs).
      Though GAGs are known to play a major role in maintaining compressive integrity
      in GAG-rich tissues such as articular cartilage, their role in fibrocartilaginous
      tissues in which GAGs are much less abundant is not clearly defined. Therefore,
      this study investigates the contribution of GAGs to the regional viscoelastic
      compressive properties of the temporomandibular joint (TMJ) disc. Chondroitinase
      ABC (C-ABC) was used to deplete GAGs in five different disc regions, and the time
      course for >95% GAG removal was defined. The compressive properties of GAG
      depleted regional specimens were then compared to non-treated controls using an
      unconfined compression stress-relaxation test. Additionally, treated and non
      treated specimens were assayed biochemically and histologically to confirm GAG
      removal. Compared to untreated controls, the only regions affected by GAG removal
      in terms of biomechanical properties were in the intermediate zone, the most GAG
      rich portion of the disc. Without GAGs, all intermediate zone regions showed
      decreased tissue viscosity, and the intermediate zone lateral region also showed
      a 12.5% decrease in modulus of relaxation. However, in the anterior and posterior
      band regions, no change in compressive properties was observed following GAG
      depletion, though these regions showed the highest compressive properties
      overall. Although GAGs are not the major extracellular matrix molecule of the TMJ
      disc, they are responsible for some of the viscoelastic compressive properties of
      the tissue. Furthermore, the mechanical role of sulfated GAGs in the disc varies
      regionally in the tissue, and GAG abundance does not always correlate with higher
      compressive properties. Overall, this study found that sulfated GAGs are
      important to TMJ disc mechanics in the intermediate zone, an important finding
      for establishing design characteristics for future tissue engineering efforts.

PMID- 22482667
TI  - Assessment of energy requirement for the retinal arterial network in normal and
      hypertensive subjects.
AB  - The retinal arterial network structure can be altered by systemic diseases such
      as hypertension and diabetes. In order to compare the energy requirement for
      maintaining retinal blood flow and vessel wall metabolism between normal and
      hypertensive subjects, 3D hypothetical models of a representative retinal
      arterial bifurcation were constructed based on topological features derived from
      retinal images. Computational analysis of blood flow was performed, which
      accounted for the non-Newtonian rheological properties of blood and peripheral
      vessel resistance. The results suggested that the rate of energy required to
      maintain the blood flow and wall metabolism is much lower for normal subjects
      than for hypertensives, with the latter requiring 49.2% more energy for an entire
      retinal arteriolar tree. Among the several morphological factors, length-to
      diameter ratio was found to have the most significant influence on the overall
      energy requirement.

PMID- 22482668
TI  - Partial meniscectomy changes fluid pressurization in articular cartilage in human
      knees.
AB  - Partial meniscectomy is believed to change the biomechanics of the knee joint
      through alterations in the contact of articular cartilages and menisci. Although
      fluid pressure plays an important role in the load support mechanism of the knee,
      the fluid pressurization in the cartilages and menisci has been ignored in the
      finite element studies of the mechanics of meniscectomy. In the present study, a
      3D fibril-reinforced poromechanical model of the knee joint was used to explore
      the fluid flow dependent changes in articular cartilage following partial medial
      and lateral meniscectomies. Six partial longitudinal meniscectomies were
      considered under relaxation, simple creep, and combined creep loading conditions.
      In comparison to the intact knee, partial meniscectomy not only caused a
      substantial increase in the maximum fluid pressure but also shifted the location
      of this pressure in the femoral cartilage. Furthermore, these changes were
      positively correlated to the size of meniscal resection. While in the intact
      joint, the location of the maximum fluid pressure was dependent on the loading
      conditions, in the meniscectomized joint the location was predominantly
      determined by the site of meniscal resection. The partial meniscectomy also
      reduced the rate of the pressure dissipation, resulting in even larger difference
      between creep and relaxation times as compared to the case of the intact knee.
      The knee joint became stiffer after meniscectomy because of higher fluid pressure
      at knee compression followed by slower pressure dissipation. The present study
      indicated the role of fluid pressurization in the altered mechanics of
      meniscectomized knees.

PMID- 22482669
TI  - Investigation of saccadic eye movement effects on the fluid dynamic in the
      anterior chamber.
AB  - The aqueous humor (AH) flow in the anterior chamber (AC) due to saccadic
      movements is investigated in this research. The continuity, Navier-Stokes and
      energy equations in 3D and unsteady forms are solved numerically and the saccadic
      motion was modeled by the dynamic mesh technique. Firstly, the numerical model
      was validated for the saccadic movement of a spherical cavity with analytic
      solutions and experimental data where excellent agreement was observed. Then, two
      types of periodic and realistic saccadic motions of the AC are simulated, whereby
      the flow field is computed for various saccade amplitudes and the results are
      reported for different times. The results show that the acting shear stress on
      the corneal endothelial cells from AH due to saccadic movements is much higher
      than that due to normal AH flow by buoyancy induced due to temperature gradient.
      This shear stress is higher on the central region of the cornea. The results also
      depict that eye saccade imposes a 3D complicated flow field in the AC consist of
      various vortex structures. Finally, the enchantment of heat transfer in the AC by
      AH mixing as a result of saccadic motion is investigated.

PMID- 22482670
TI  - Computational modeling of shear-based hemolysis caused by renal obstruction.
AB  - As endovascular treatment of abdominal aortic aneurysms (AAAs) gains popularity,
      it is becoming possible to treat certain challenging aneurysmal anatomies with
      endografts relying on suprarenal fixation. In such anatomies, the bare struts of
      the device may be placed across the renal artery ostia, causing partial
      obstruction to renal artery blood flow. Computational fluid dynamics (CFD) was
      used to simulate blood flow from the aorta to the renal arteries, utilizing
      patient-specific boundary conditions, in three patient models and calculate the
      degree of shear-based blood damage (hemolysis). We used contrast-enhanced
      computed tomography angiography (CTA) data from three AAA patients who were
      treated with a novel endograft to build patient-specific models. For each of the
      three patients, we constructed a baseline model and endoframe model. The baseline
      model was a direct representation of the patient's 30-day post-operative CTA
      data. This model was then altered to create the endoframe model, which included a
      ring of metallic struts across the renal artery ostia. CFD was used to simulate
      blood flow, utilizing patient-specific boundary conditions. Pressures, flows,
      shear stresses, and the normalized index of hemolysis (NIH) were quantified for
      all patients. The overall differences between the baseline and endoframe models
      for all three patients were minimal, as measured though pressure, volumetric
      flow, velocity, and shear stress. The average NIH across the three baseline and
      endoframe models was 0.002 and 0.004, respectively. Results of CFD modeling show
      that the overall disturbance to flow caused by the presence of the endoframe
      struts is minimal. The magnitude of the NIH in all models was well below the
      accepted design and safety threshold for implantable medical devices that
      interact with blood flow.

PMID- 22482671
TI  - Biaxial tensile testing and constitutive modeling of human supraspinatus tendon.
AB  - The heterogeneous composition and mechanical properties of the supraspinatus
      tendon offer an opportunity for studying the structure-function relationships of
      fibrous musculoskeletal connective tissues. Previous uniaxial testing has
      demonstrated a correlation between the collagen fiber angle distribution and
      tendon mechanics in response to tensile loading both parallel and transverse to
      the tendon longitudinal axis. However, the planar mechanics of the supraspinatus
      tendon may be more appropriately characterized through biaxial tensile testing,
      which avoids the limitation of nonphysiologic traction-free boundary conditions
      present during uniaxial testing. Combined with a structural constitutive model,
      biaxial testing can help identify the specific structural mechanisms underlying
      the tendon's two-dimensional mechanical behavior. Therefore, the objective of
      this study was to evaluate the contribution of collagen fiber organization to the
      planar tensile mechanics of the human supraspinatus tendon by fitting biaxial
      tensile data with a structural constitutive model that incorporates a sample
      specific angular distribution of nonlinear fibers. Regional samples were tested
      under several biaxial boundary conditions while simultaneously measuring the
      collagen fiber orientations via polarized light imaging. The histograms of fiber
      angles were fit with a von Mises probability distribution and input into a
      hyperelastic constitutive model incorporating the contributions of the uncrimped
      fibers. Samples with a wide fiber angle distribution produced greater transverse
      stresses than more highly aligned samples. The structural model fit the
      longitudinal stresses well (median R(2) >= 0.96) and was validated by
      successfully predicting the stress response to a mechanical protocol not used for
      parameter estimation. The transverse stresses were fit less well with greater
      errors observed for less aligned samples. Sensitivity analyses and relatively
      affine fiber kinematics suggest that these errors are not due to inaccuracies in
      measuring the collagen fiber organization. More likely, additional strain energy
      terms representing fiber-fiber interactions are necessary to provide a closer
      approximation of the transverse stresses. Nevertheless, this approach
      demonstrated that the longitudinal tensile mechanics of the supraspinatus tendon
      are primarily dependent on the moduli, crimp, and angular distribution of its
      collagen fibers. These results add to the existing knowledge of structure
      function relationships in fibrous musculoskeletal tissue, which is valuable for
      understanding the etiology of degenerative disease, developing effective tissue
      engineering design strategies, and predicting outcomes of tissue repair.

PMID- 22482672
TI  - A one-dimensional model of the spinal cerebrospinal-fluid compartment.
AB  - Modeling of the cerebrospinal fluid (CSF) system in the spine is strongly
      motivated by the need to understand the origins of pathological conditions such
      as the emergence and growth of fluid-filled cysts in the spinal cord. In this
      study, a one-dimensional (1D) approximation for the flow in elastic conduits was
      used to formulate a model of the spinal CSF compartment. The modeling was based
      around a coaxial geometry in which the inner elastic cylinder represented the
      spinal cord, middle elastic tube represented the dura, and the outermost tube
      represented the vertebral column. The fluid-filled annuli between the cord and
      dura, and the dura and vertebral column, represented the subarachnoid and
      epidural spaces, respectively. The system of governing equations was constructed
      by applying a 1D form of mass and momentum conservation to all segments of the
      model. The developed 1D model was used to simulate CSF pulse excited by pressure
      disturbances in the subarachnoid and epidural spaces. The results were compared
      to those obtained from an equivalent two-dimensional finite element (FE) model
      which was implemented using a commercial software package. The analysis of
      linearized governing equations revealed the existence of three types of waves, of
      which the two slower waves can be clearly related to the wave modes identified in
      previous similar studies. The third, much faster, wave emanates directly from the
      vertebral column and has little effect on the deformation of the spinal cord. The
      results obtained from the 1D model and its FE counterpart were found to be in
      good general agreement even when sharp spatial gradients of the spinal cord
      stiffness were included; both models predicted large radial displacements of the
      cord at the location of an initial cyst. This study suggests that 1D modeling,
      which is computationally inexpensive and amenable to coupling with the models of
      the cranial CSF system, should be a useful approach for the analysis of some
      aspects of the CSF dynamics in the spine. The simulation of the CSF pulse excited
      by a pressure disturbance in the epidural space, points to the possibility that
      regions of the spinal cord with abnormally low stiffness may be prone to
      experiencing large strains due to coughing and sneezing.

PMID- 22482673
TI  - A surface roughness comparison of cartilage in different types of synovial
      joints.
AB  - The naturally occurring structure of articular cartilage has proven to be an
      effective means for the facilitation of motion and load support in equine and
      other animal joints. For this reason, cartilage has been extensively studied for
      many years. Although the roughness of cartilage has been determined from atomic
      force microscopy (AFM) and other methods in multiple studies, a comparison of
      roughness to joint function has not be completed. It is hypothesized that various
      joint types with different motions and regimes of lubrication have altered
      demands on the articular surface that may affect cartilage surface properties.
      Micro- and nanoscale stylus profilometry was performed on the carpal cartilage
      harvested from 16 equine forelimbs. Eighty cartilage surface samples taken from
      three different functioning joint types (radiocarpal, midcarpal, and
      carpometacarpal) were measured by a Veeco Dektak 150 Stylus Surface Profilometer.
      The average surface roughness measurements were statistically different for each
      joint. This indicates that the structure of cartilage is adapted to, or worn by,
      its operating environment. Knowledge of cartilage micro- and nanoscale roughness
      will assist the future development and design of treatments for intra- articular
      substances or surfaces to preserve joint integrity and reduce limitations or loss
      of joint performance.

PMID- 22482674
TI  - Nanoindentation measurements of biomechanical properties in mature and newly
      formed bone tissue surrounding an implant.
AB  - The characterization of the biomechanical properties of newly formed bone tissue
      around implants is important to understand the osseointegration process. The
      objective of this study is to investigate the evolution of the hardness and
      indentation modulus of newly formed bone tissue as a function of healing time. To
      do so, a nanoindentation device is employed following a multimodality approach
      using histological analysis. Coin-shaped implants were placed in vivo at a
      distance of 200 MUm from the cortical bone surface, leading to an initially empty
      cavity of 200 MUm * 4.4 mm. Three New Zealand White rabbits were sacrificed after
      4, 7, and 13 weeks of healing time. The bone samples were embedded and analyzed
      using histological analyses, allowing to distinguish mature and newly formed bone
      tissue. The bone mechanical properties were then measured in mature and newly
      formed bone tissue. The results are within the range of hardness and apparent
      Young's modulus values reported in previous literature. One-way ANOVA test
      revealed a significant effect of healing time on the indentation modulus (p <
      0.001, F = 111.24) and hardness (p < 0.02, F = 3.47) of bone tissue. A Tukey
      Kramer analysis revealed that the biomechanical properties of newly formed bone
      tissue (4 weeks) were significantly different from those of mature bone tissue.
      The comparison with the results obtained in Mathieu et al. (2011, "Micro
      Brillouin Scattering Measurements in Mature and Newly Formed Bone Tissue
      Surrounding an Implant," J. Biomech. Eng., 133, 021006). shows that bone mass
      density increases by approximately 13.5% between newly formed bone (7 weeks) and
      mature bone tissue.

PMID- 22482675
TI  - A mechanical characterization of the porcine atria at the healthy stage and after
      ventricular tachypacing.
AB  - Atrial fibrillation (AF) is a cardiac arrhythmia that highly increases the risk
      of stroke and is associated with significant but still unexplored changes in the
      mechanical behavior of the tissue. Planar biaxial tests were performed on tissue
      specimens from pigs at the healthy stage and after ventricular tachypacing (VTP),
      a procedure applied to reproduce the relevant features of AF. The local
      arrangement of the fiber bundles in the tissue was investigated on specimens from
      rabbit atria by means of circularly polarized light. Based on this, mechanical
      data were fitted to two anisotropic constitutive relationships, including a four
      parameter Fung-type model and a microstructurally-motivated model. Accounting for
      the fiber-induced anisotropy brought average R(2) = 0.807 for the
      microstructurally-motivated model and average R(2) = 0.949 for the Fung model.
      Validation of the fitted constitutive relationships was performed by means of FEM
      simulations coupled to FORTRAN routines. The performances of the two material
      models in predicting the second Piola-Kirchhoff stress were comparable, with
      average errors <3.1%. However, the Fung model outperformed the other in the
      prediction of the Green-Lagrange strain, with 9.2% maximum average error. To
      increase model generality, a proper averaging procedure accounting for
      nonlinearities was used to obtain average material parameters. In general, a
      stiffer behavior after VTP was noted.

PMID- 22482676
TI  - The biomechanical effect of torsion on humeral shaft repair techniques for
      completed pathological fractures.
AB  - In the presence of a tumor defect, completed humeral shaft fractures continue to
      be a major surgical challenge since there is no "gold standard" treatment. This
      is due, in part, to the fact that only one prior biomechanical study exists on
      the matter, but which only compared 2 repair methods. The current authors
      measured the humeral torsional performance of 5 fixation constructs for completed
      pathological fractures. In 40 artificial humeri, a 2-cm hemi-cylindrical cortical
      defect with a transverse fracture was created in the lateral cortex. Specimens
      were divided into 5 different constructs and tested in torsion. Construct A was a
      broad 10-hole 4.5-mm dynamic compression plate (DCP). Construct B was the same as
      A except that the screw holes and the tumor defect were filled with bone cement
      and the screws were inserted into soft cement. Construct C was the same as A
      except that the canal and tumor defect were filled with bone cement and the
      screws were inserted into dry cement. Construct D was a locked intramedullary
      nail inserted in the antegrade direction. Construct E was the same as D except
      that bone cement filled the defect. For torsional stiffness, construct C (4.45 +/
      0.20 Nm/deg) was not different than B or E (p > 0.16), but was higher than A and
      D (p < 0.001). For failure torque, construct C achieved a higher failure torque
      (69.65 +/- 5.35 Nm) than other groups (p < 0.001). For the failure angle, there
      were no differences between plating constructs A to C (p >= 0.11), except for B
      versus C (p < 0.05), or between nailing groups D versus E (p = 0.97), however,
      all plating groups had smaller failure angles than both nailing groups (p <
      0.05). For failure energy, construct C (17.97 +/- 3.59 J) had a higher value than
      other groups (p < 0.005), except for A (p = 0.057). Torsional failure always
      occurred in the bone in the classic "spiral" pattern. Construct C provided the
      highest torsional stability for a completed pathological humeral shaft fracture.

PMID- 22482677
TI  - Viscoelastic material properties of the myocardium and cardiac jelly in the
      looping chick heart.
AB  - Accurate material properties of developing embryonic tissues are a crucial factor
      in studies of the mechanics of morphogenesis. In the present work, we
      characterize the viscoelastic material properties of the looping heart tube in
      the chick embryo through nonlinear finite element modeling and microindentation
      experiments. Both hysteresis and ramp-hold experiments were performed on the
      intact heart and isolated cardiac jelly (extracellular matrix). An inverse
      computational method was used to determine the constitutive relations for the
      myocardium and cardiac jelly. With both layers assumed to be quasilinear
      viscoelastic, material coefficients for an Ogden type strain-energy density
      function combined with Prony series of two terms or less were determined by
      fitting numerical results from a simplified model of a heart segment to
      experimental data. The experimental and modeling techniques can be applied
      generally for determining viscoelastic material properties of embryonic tissues.

PMID- 22482678
TI  - A semi-empirical cell dynamics model for bone turnover under external stimulus.
AB  - The normal periodic turnover of bone is referred to as remodeling. In remodeling,
      old or damaged bone is removed during a 'resorption' phase and new bone is formed
      in its place during a 'formation' phase in a sequence of events known as
      coupling. Resorption is preceded by an 'activation' phase in which the signal to
      remodel is initiated and transmitted. Remodeling is known to involve the
      interaction of external stimuli, bone cells, calcium and phosphate ions, and
      several proteins, hormones, molecules, and factors. In this study, a semi
      empirical cell dynamics model for bone remodeling under external stimulus that
      accounts for the interaction between bone mass, bone fluid calcium, bone calcium,
      and all three major bone cell types, is presented. The model is formulated to
      mimic biological coupling by solving separately and sequentially systems of ODEs
      for the activation, resorption, and formation phases of bone remodeling. The
      charateristic time for resorption (20 days) and the amount of resorption (~0.5%)
      are fixed for all simulations, but the formation time at turnover is an output of
      the model. The model was used to investigate the effects of different types of
      strain stimuli on bone turnover under bone fluid calcium balance and imbalance
      conditions. For bone fluid calcium balance, the model predicts complete turnover
      after 130 days of formation under constant 1000 microstrain stimulus; after 47
      days of formation under constant 2000 microstrain stimulus; after 173 days of
      formation under strain-free conditions, and after 80 days of formation under
      monotonic increasing strain stimulus from 1000 to 2000 microstrain. For bone
      fluid calcium imbalance, the model predicts that complete turnover occurs after
      261 days of formation under constant 1000 microstrain stimulus and that turnover
      never occurs under strain-free conditions. These predictions were not impacted by
      mean dynamic input strain stimuli of 1000 and 2000 microstrain at 1 Hz and 1000
      microstrain amplitude. The formation phase of remodeling lasts longer than the
      resorption phase, increased strain stimulus accelerates bone turnover, while
      absence of strain significantly delays or prevents it, and formation time for
      turnover under monotonic increasing strain conditions is intermediate to those
      for constant strain stimuli at the minimum and maximum monotonic strain levels.
      These results are consistent with the biology, and with Frost's mechanostat
      theory.

PMID- 22482679
TI  - Tendon strain measurements with dynamic ultrasound images: evaluation of digital
      image correlation.
AB  - Strain is an essential metric in tissue mechanics. Strains and strain
      distributions during functional loads can help identify damaged and pathologic
      regions as well as quantify functional compromise. Noninvasive strain measurement
      in vivo is difficult to perform. The goal of this in vitro study is to determine
      the efficacy of digital image correlation (DIC) methods to measure strain in B
      mode ultrasound images. The Achilles tendons of eight male Wistar rats were
      removed and mechanically cycled between 0 and 1% strain. Three cine video images
      were captured for each specimen: (1) optical video for manual tracking of optical
      markers; (2) optical video for DIC tracking of optical surface markers; and (3)
      ultrasound video for DIC tracking of image texture within the tissue. All three
      imaging modalities were similarly able to measure tendon strain during cyclic
      testing. Manual/ImageJ-based strain values linearly correlated with DIC (optical
      marker)-based strain values for all eight tendons with a slope of 0.970. DIC
      (optical marker)-based strain values linearly correlated with DIC (ultrasound
      texture)-based strain values for all eight tendons with a slope of 1.003. Strain
      measurement using DIC was as accurate as manual image tracking methods, and DIC
      tracking was equally accurate when tracking ultrasound texture as when tracking
      optical markers. This study supports the use of DIC to calculate strains directly
      from the texture present in standard B-mode ultrasound images and supports the
      use of DIC for in vivo strain measurement using ultrasound images without
      additional markers, either artificially placed (for optical tracking) or
      anatomically in view (i.e., bony landmarks and/or muscle-tendon junctions).

PMID- 22482680
TI  - A study on the effects of covered stents on tissue prolapse.
AB  - Polyvinyl alcohol (PVA) cryogel covered stents may reduce complications from
      thrombosis and restenosis by decreasing tissue prolapse. Finite element analysis
      was employed to evaluate the effects of PVA cryogel layers of varying thickness
      on tissue prolapse and artery wall stress for two common stent geometries and two
      vessel diameters. Additionally, several PVA cryogel covered stents were
      fabricated and imaged with an environmental scanning electron microscope. Finite
      element results showed that covered stents reduced tissue prolapse up to 13% and
      artery wall stress up to 29% with the size of the reduction depending on the
      stent geometry, vessel diameter, and PVA cryogel layer thickness. Environmental
      scanning electron microscope images of expanded covered stents showed the PVA
      cryogel to completely cover the area between struts without gaps or tears.
      Overall, this work provides both computational and experimental evidence for the
      use of PVA cryogels in covered stents.

PMID- 22482681
TI  - In vitro articular cartilage growth with sequential application of IGF-1 and TGF
      beta1 enhances volumetric growth and maintains compressive properties.
AB  - In vitro cultures with insulin-like growth factor-1 (IGF-1) and transforming
      growth factor-beta1 (TGF-beta1) have previously been shown to differentially
      modulate the growth of immature bovine articular cartilage. IGF-1 stimulates
      expansive growth yet decreases compressive moduli and increases compressive
      Poisson's ratios, whereas TGF-beta1 maintains tissue size, increases compressive
      moduli, and decreases compressive Poisson's ratios. The current study's
      hypothesis was that sequential application of IGF-1 and TGF-beta1 during in vitro
      culture produces geometric and compressive mechanical properties that lie between
      extreme values produced when using either growth factor alone. Immature bovine
      articular cartilage specimens were harvested and either untreated (D0, i.e., day
      zero) or cultured in vitro for either 6 days with IGF-1 (D6 IGF), 12 days with
      IGF-1 (D12 IGF), or 6 days with IGF-1 followed by 6 days with TGF-beta1 (D12 SEQ,
      i.e., sequential). Following treatment, all specimens were tested for geometric,
      biochemical, and compressive mechanical properties. Relative to D0, D12 SEQ
      treatment enhanced volumetric growth, but to a lower value than that for D12 IGF.
      Furthermore, D12 SEQ treatment maintained compressive moduli and Poisson's ratios
      at values higher and lower, respectively, than those for D12 IGF. Considering the
      previously described effects of 12 days of treatment with TGF-beta1 alone, D12
      SEQ induced both growth and mechanical property changes between those produced
      with either IGF-1 or TGF-beta1 alone. The results suggest that it may be possible
      to vary the durations of select growth factors, including IGF-1 and TGF-beta1, to
      more precisely modulate the geometric, biochemical, and mechanical properties of
      immature cartilage graft tissue in clinical repair strategies.

PMID- 22482682
TI  - A three-dimensional inverse finite element analysis of the heel pad.
AB  - Quantification of plantar tissue behavior of the heel pad is essential in
      developing computational models for predictive analysis of preventive treatment
      options such as footwear for patients with diabetes. Simulation based studies in
      the past have generally adopted heel pad properties from the literature, in
      return using heel-specific geometry with material properties of a different heel.
      In exceptional cases, patient-specific material characterization was performed
      with simplified two-dimensional models, without further evaluation of a heel
      specific response under different loading conditions. The aim of this study was
      to conduct an inverse finite element analysis of the heel in order to calculate
      heel-specific material properties in situ. Multidimensional experimental data
      available from a previous cadaver study by Erdemir et al. ("An Elaborate Data Set
      Characterizing the Mechanical Response of the Foot," ASME J. Biomech. Eng.,
      131(9), pp. 094502) was used for model development, optimization, and evaluation
      of material properties. A specimen-specific three-dimensional finite element
      representation was developed. Heel pad material properties were determined using
      inverse finite element analysis by fitting the model behavior to the experimental
      data. Compression dominant loading, applied using a spherical indenter, was used
      for optimization of the material properties. The optimized material properties
      were evaluated through simulations representative of a combined loading scenario
      (compression and anterior-posterior shear) with a spherical indenter and also of
      a compression dominant loading applied using an elevated platform. Optimized heel
      pad material coefficients were 0.001084 MPa (MU), 9.780 (alpha) (with an
      effective Poisson's ratio (nu) of 0.475), for a first-order nearly incompressible
      Ogden material model. The model predicted structural response of the heel pad was
      in good agreement for both the optimization (<1.05% maximum tool force, 0.9%
      maximum tool displacement) and validation cases (6.5% maximum tool force, 15%
      maximum tool displacement). The inverse analysis successfully predicted the
      material properties for the given specimen-specific heel pad using the
      experimental data for the specimen. The modeling framework and results can be
      used for accurate predictions of the three-dimensional interaction of the heel
      pad with its surroundings.

PMID- 22482683
TI  - Mechanical characterization of porcine corneas.
AB  - An experimental program has been carried out in order to investigate the
      mechanical behavior of porcine corneas. We report the results of inflation tests
      on the whole cornea and uniaxial tests on excised corneal strips, performed on 51
      fresh porcine eyes. Uniaxial tests have been performed on specimens cut from
      previously inflated corneas. The cornea behavior is characterized by means of
      elastic stiffness, measured on both average pressure-apex displacement and
      average uniaxial stress-strain curves; and by means of transversal contraction
      coefficient, peak stress, and failure stress measured on uniaxial stress-strain
      curves. Uniaxial tests performed on excised strips allowed to measure the
      anisotropy in the corneal stiffness and to compare the stiffness of the cornea
      with the one of the sclera. Viscous properties of the cornea have been obtained
      through uniaxial relaxation curves on excised corneal strips. The relevant
      geometrical parameters have been measured and, with the aid of the elastic thin
      shell theory, a stress-strain curve has been derived from the average inflation
      test data and compared with similar data available in the literature. The
      experimental system has been developed in view of future applications to the
      mechanical testing of both porcine and human corneas.

PMID- 22482684
TI  - Multiscale design and multiobjective optimization of orthopedic hip implants with
      functionally graded cellular material.
AB  - Revision surgeries of total hip arthroplasty are often caused by a deficient
      structural compatibility of the implant. Two main culprits, among others, are
      bone-implant interface instability and bone resorption. To address these issues,
      in this paper we propose a novel type of implant, which, in contrast to current
      hip replacement implants made of either a fully solid or a foam material,
      consists of a lattice microstructure with nonhomogeneous distribution of material
      properties. A methodology based on multiscale mechanics and design optimization
      is introduced to synthesize a graded cellular implant that can minimize
      concurrently bone resorption and implant interface failure. The procedure is
      applied to the design of a 2D left implanted femur with optimized gradients of
      relative density. To assess the manufacturability of the graded cellular
      microstructure, a proof-of-concept is fabricated by using rapid prototyping. The
      results from the analysis are used to compare the optimized cellular implant with
      a fully dense titanium implant and a homogeneous foam implant with a relative
      density of 50%. The bone resorption and the maximum value of interface stress of
      the cellular implant are found to be over 70% and 50% less than the titanium
      implant while being 53% and 65% less than the foam implant.

PMID- 22482686
TI  - Syrinx fluid transport: modeling pressure-wave-induced flux across the spinal
      pial membrane.
AB  - Syrinxes are fluid-filled cavities of the spinal cord that characterize
      syringomyelia, a disease involving neurological damage. Their formation and
      expansion is poorly understood, which has hindered successful treatment. Syrinx
      cavities are hydraulically connected with the spinal subarachnoid space (SSS)
      enveloping the spinal cord via the cord interstitium and the network of
      perivascular spaces (PVSs), which surround blood vessels penetrating the pial
      membrane that is adherent to the cord surface. Since the spinal canal supports
      pressure wave propagation, it has been hypothesized that wave-induced fluid
      exchange across the pial membrane may play a role in syrinx filling. To
      investigate this conjecture a pair of one-dimensional (1-d) analytical models
      were developed from classical elastic tube theory coupled with Darcy's law for
      either perivascular or interstitial flow. The results show that transpial flux
      serves as a mechanism for damping pressure waves by alleviating hoop stress in
      the pial membrane. The timescale ratio over which viscous and inertial forces
      compete was explicitly determined, which predicts that dilated PVS, SSS flow
      obstructions, and a stiffer and thicker pial membrane-all associated with
      syringomyelia-will increase transpial flux and retard wave travel. It was also
      revealed that the propagation of a pressure wave is aided by a less-permeable
      pial membrane and, in contrast, by a more-permeable spinal cord. This is the
      first modeling of the spinal canal to include both pressure-wave propagation
      along the spinal axis and a pathway for fluid to enter and leave the cord, which
      provides an analytical foundation from which to approach the full poroelastic
      problem.

PMID- 22482685
TI  - Influence of decorin on the mechanical, compositional, and structural properties
      of the mouse patellar tendon.
AB  - The interactions of small leucine-rich proteoglycans (SLRPs) with collagen
      fibrils, their association with water, and their role in fibrillogenesis suggests
      that SLRPs may play an important role in tendon mechanics. Some studies have
      assessed the role of SLRPs in the mechanical response of the tendon, but the
      relationships between sophisticated mechanics, assembly of collagen, and SLRPs
      have not been well characterized. Decorin content was varied in a dose dependent
      manner using decorin null, decorin heterozygote, and wild type mice. Quantitative
      measures of mechanical (tension and compression), compositional, and structural
      changes of the mouse patellar tendon were evaluated. Viscoelastic, tensile
      dynamic modulus was increased in the decorin heterozygous tendons compared to
      wild type. These tendons also had a significant decrease in total collagen and no
      structural changes compared to wild type. Decorin null tendons did not have any
      mechanical changes; however, a significant decrease in the average fibril
      diameter was found. No differences were seen between genotypes in elastic or
      compressive properties, and all tendons demonstrated viscoelastic mechanical
      dependence on strain rate and frequency. These results suggest that decorin, a
      member of the SLRP family, plays a role in tendon viscoelasticity that cannot be
      completely explained by its role in collagen fibrillogenesis. In addition,
      reductions in decorin do not cause large changes in indentation compressive
      properties, suggesting that other factors contribute to these properties.
      Understanding these relationships may ultimately help guide development of tissue
      engineered constructs or treatment modalities.

PMID- 22482687
TI  - Effect of preconditioning and stress relaxation on local collagen fiber re
      alignment: inhomogeneous properties of rat supraspinatus tendon.
AB  - Repeatedly and consistently measuring the mechanical properties of tendon is
      important but presents a challenge. Preconditioning can provide tendons with a
      consistent loading history to make comparisons between groups from mechanical
      testing experiments. However, the specific mechanisms occurring during
      preconditioning are unknown. Previous studies have suggested that microstructural
      changes, such as collagen fiber re-alignment, may be a result of preconditioning.
      Local collagen fiber re-alignment is quantified throughout tensile mechanical
      testing using a testing system integrated with a polarized light setup,
      consisting of a backlight, 90 deg-offset rotating polarizer sheets on each side
      of the test sample, and a digital camera, in a rat supraspinatus tendon model,
      and corresponding mechanical properties are measured. Local circular variance
      values are compared throughout the mechanical test to determine if and where
      collagen fiber re-alignment occurred. The inhomogeneity of the tendon is examined
      by comparing local circular variance values, optical moduli and optical
      transition strain values. Although the largest amount of collagen fiber re
      alignment was found during preconditioning, significant re-alignment was also
      demonstrated in the toe and linear regions of the mechanical test. No significant
      changes in re-alignment were seen during stress relaxation. The insertion site of
      the supraspinatus tendon demonstrated a lower linear modulus and a more
      disorganized collagen fiber distribution throughout all mechanical testing points
      compared to the tendon midsubstance. This study identified a correlation between
      collagen fiber re-alignment and preconditioning and suggests that collagen fiber
      re-alignment may be a potential mechanism of preconditioning and merits further
      investigation. In particular, the conditions necessary for collagen fibers to re
      orient away from the direction of loading and the dependency of collagen
      reorganization on its initial distribution must be examined.

PMID- 22482688
TI  - Procedure to estimate thermophysical and geometrical parameters of embedded
      cancerous lesions using thermography.
AB  - Based on the fact that malignant cancerous lesions (neoplasms) develop high
      metabolism and use more blood supply than normal tissue, infrared thermography
      (IR) has become a reliable clinical technique used to indicate noninvasively the
      presence of cancerous diseases, e.g., skin and breast cancer. However, to
      diagnose cancerous diseases by IR, the technique requires procedures that explore
      the relationship between the neoplasm characteristics (size, blood perfusion rate
      and heat generated) and the resulting temperature distribution on the skin
      surface. In this research work the dual reciprocity boundary element method
      (DRBEM) has been coupled with the simulated annealing technique (SA) in a new
      inverse procedure, which coupled to the IR technique, is capable of estimating
      simultaneously geometrical and thermophysical parameters of the neoplasm. The
      method is of an evolutionary type, requiring random initial values for the
      unknown parameters and no calculations of sensitivities or search directions. In
      addition, the DRBEM does not require any re-meshing at each proposed solution to
      solve the bioheat model. The inverse procedure has been tested considering input
      data for simulated neoplasms of different sizes and positions in relation to the
      skin surface. The successful estimation of unknown neoplasm parameters validates
      the idea of using the SA technique and the DRBEM in the estimation of parameters.
      Other estimation techniques, based on genetic algorithms or sensitivity
      coefficients, have not been capable of obtaining a solution because the skin
      surface temperature difference is very small.

PMID- 22482689
TI  - A model-free feature-based bi-planar RSA method for kinematic analysis of total
      knee arthroplasty.
AB  - Fluoroscopic imaging is commonly used for assessing relative motions of
      orthopaedic implants. One limiting factor to in vivo model-based roentgen
      stereophotogrammetric analysis of total knee arthroplasty is the need for 3D
      models of the implants.The 3D models of the implant components must be reverse
      engineered, if not provided by the company, which makes this method impractical
      for a clinical study involving many types or sizes of implants. This study
      introduces a novel feature-based methodology that registers the features at the
      implant-bone or implant-cement interface of the components that have elementary
      shapes. These features include pegs with hemispherical heads, and straight,
      circular or curved edges located on flat faces of the box of the femoral
      component or the stem geometry of the tibial component. Software was developed to
      allow easy registration of these features through a graphical user interface. The
      accuracy and precision of registration for multiple flexion angles from 0 to 120
      deg was determined with reference to registered poses of the implants through
      experiments on bone replica models and also on a cadaver specimen implanted with
      total knee prostheses. When compared to an equivalent bi-planar model-based
      registration, the results were comparable: The mean accuracy of this feature
      based method was 1.45 deg and 1.03 mm (in comparison to 0.95 deg and 1.32 mm for
      the model-based approach), and the mean precision was 0.57 deg and 0.26 mm (in
      comparison to 0.42 deg and 0.44 mm for the model-based approach).The methodology
      and the developed software can easily accommodate different design of implants
      with various fixation features. This method can facilitate in vivo kinematic
      analysis of total knee arthroplasty by eliminating the need for 3D models of the
      implant components.

PMID- 22482690
TI  - Evolution of acoustically vaporized microdroplets in gas embolotherapy.
AB  - Acoustic vaporization dynamics of a superheated dodecafluoropentane (DDFP)
      microdroplet inside a microtube and the resulting bubble evolution is
      investigated in the present work. This work is motivated by a developmental gas
      embolotherapy technique that is intended to treat cancers by infarcting tumors
      using gas bubbles. A combined theoretical and computational approach is utilized
      and compared with the experiments to understand the evolution process and to
      estimate the resulting stress distribution associated with vaporization event.
      The transient bubble growth is first studied by ultra-high speed imaging and then
      theoretical and computational modeling is used to predict the entire bubble
      evolution process. The evolution process consists of three regimes: an initial
      linear rapid spherical growth followed by a linear compressed oval shaped growth
      and finally a slow asymptotic nonlinear spherical bubble growth. Although the
      droplets are small compared to the tube diameter, the bubble evolution is
      influenced by the tube wall. The final bubble radius is found to scale linearly
      with the initial droplet radius and is approximately five times the initial
      droplet radius. A short pressure pulse with amplitude almost twice as that of
      ambient conditions is observed. The width of this pressure pulse increases with
      increasing droplet size whereas the amplitude is weakly dependent. Although the
      rise in shear stress along the tube wall is found to be under peak physiological
      limits, the shear stress amplitude is found to be more prominently influenced by
      the initial droplet size. The role of viscous dissipation along the tube wall and
      ambient bulk fluid pressure is found to be significant in bubble evolution
      dynamics.

PMID- 22482691
TI  - Effect of frozen storage on dynamic tensile properties of human placenta.
AB  - Dynamic mechanical properties of placenta tissue are needed to develop
      computational models of pregnant occupants for use in designing restraint systems
      that protect the fetus and mother. Tests were performed on 21 samples obtained
      from five human placentas at a rate of 1200 %/s using a set of custom designed
      thermoelectrically cooled clamps. Approximately half of the samples from all five
      subjects were tested within 48 h of delivery. The remaining samples were frozen
      for 5-7 days and then thawed before testing. True failure stresses and strains
      were not significantly different between fresh and frozen samples (p-value =
      0.858 and 0.551, respectively), suggesting that soft tissue may be stored frozen
      up to a week without adversely affecting dynamic material response.

PMID- 22482692
TI  - Long-term declarative memory deficits in diffuse TBI: correlations with cortical
      thickness, white matter integrity and hippocampal volume.
AB  - We investigated structural brain damage in subjects who had suffered severe and
      diffuse traumatic brain injury (TBI), and examined its relationship with
      declarative memory impairment. Cortical thickness, diffusion tensor imaging
      (DTI), and volumetric and shape data of the hippocampus were assessed in a group
      of 26 adults with severe TBI in the chronic stage and 22 healthy matched
      controls. Declarative memory was evaluated by Rey's Auditory Verbal Learning Test
      (RAVLT). TBI patients performed significantly worse than controls on all RAVLT
      measures. The group comparison for cortical thickness and DTI revealed a pattern
      of widespread atrophy in TBI patients. In the TBI group DTI measures correlated
      with cortical thickness in the prefrontal and parietal regions, including the
      precuneus. Declarative memory correlated with both cortical thickness and DTI
      measures. However, although hippocampal volume was significantly decreased in TBI
      patients, no correlations were found. Multiple regression analysis of all the
      structural measures revealed that decreases in Fractional anisotropy (FA) and
      thinning of the left parietal region were the best predictors of memory
      impairment. In conclusion, cortical thickness reductions in the left hemisphere
      and a lack of white matter integrity are the main contributors to long-term
      impairment in declarative memory among patients suffering from severe and diffuse
      TBI. In this study the hippocampus did not make a significant contribution to
      memory dysfunctions, suggesting that damage to this structure is compensated for
      by other regions, with the definitive sequelae being mainly explained by
      alterations in cortico-subcortical connectivity.

PMID- 22482693
TI  - Grey and white matter correlates of picture naming: evidence from a voxel-based
      lesion analysis of the Boston Naming Test.
AB  - A number of recent studies utilizing both functional neuroimaging and lesion
      analysis techniques in neurologic patients have produced conflicting results with
      respect to the neural correlates of picture naming. Picture naming involves a
      number of cognitive processes, from visual perception/recognition to lexical
      semantic retrieval to articulation. This middle process, the ability to retrieve
      a name associated with an object, has been attributed in some cases to posterior
      portions of the left lateral temporal lobe and in other cases, to anterior
      temporal cortex. In the current study, we used voxel-based lesion symptom mapping
      (VLSM) to identify neural correlates of picture naming in a large sample of well
      characterized left hemisphere (LH) patients suffering from a range of naming
      deficits. We tested patients on the Boston Naming Test (BNT), a clinical,
      standardized measure of picture naming that is widely used in both clinical and
      research settings. We found that overall performance on the BNT was associated
      with a network of LH regions that included significant portions of the left
      anterior to posterior middle temporal gyrus (MTG) and superior temporal gyrus
      (STG) and underlying white matter, and extended into left inferior parietal
      cortex. However, when we added covariates to this analysis that controlled for
      deficits in visual recognition and motor speech in order to isolate brain regions
      specific to lexical-semantic retrieval, the significant regions that remained
      were confined almost exclusively to the left mid-posterior MTG and underlying
      white matter. These findings support the notion that a large network in left peri
      Sylvian cortex supports picture naming, but that the left mid-posterior MTG and
      underlying white matter play a critical role in the core ability to retrieve a
      name associated with an object or picture.

PMID- 22482694
TI  - Development of the optic radiations and visual function after premature birth.
AB  - INTRODUCTION: Visual impairment in preterm infants at term equivalent age (TEA)
      is associated with impaired microstructural development in the optic radiation,
      measured as reduced fractional anisotropy (FA) by Diffusion Tensor Imaging (DTI).
      We tested the hypothesis that these abnormalities develop during the late preterm
      period. METHODS: DTI was performed in 53 infants born at a median (range) of
      30(+1) (25(+4)-34(+6)) weeks post-menstrual age (PMA), 22 of whom were imaged
      twice. RESULTS: FA in the optic radiation at TEA was related to: visual function
      (p = .003); PMA at birth (p = .015); and PMA at scan (p = .008); while a
      significant interaction between PMA at birth and scan (p = .019) revealed an
      effect of the period of premature extra-uterine life additional to the degree of
      prematurity. We explored this further in a sub-group of 22 infants who were
      studied twice. FA increased from mean (95% CI) .174 (.164-.176) on the first
      image at 32(+5) (29(+5)-36) weeks PMA, to .198 (.190-.206) on the second image at
      40(+6) (39(+2)-46) weeks PMA. Visual function was not predicted by FA on the
      images obtained in the early neonatal period, but was significantly related to
      the rate of increase in FA between scans (p = .027) and to FA on the second image
      (p = .015). CONCLUSION: Microstructural maturation during the late preterm period
      is thus required for normal visual function, suggesting that interventions
      applied after 30 weeks PMA might reduce impairment in preterm infants.

PMID- 22482696
TI  - Solvation and spectra of a charge transfer solute in ethanol confined within
      nanoscale silica pores.
AB  - The free energy and electronic fluorescence spectra of a model solute solvated by
      ethanol in a nanoscale silica pore are examined as a function of the solute
      position, with the aim of improving our understanding of solvation in
      nanoconfined environments. The results indicate that the position distribution of
      the solute depends on its dipole moment as well as on the surface interactions of
      the silica pore, i.e., hydrophilic or hydrophobic (uncharged). Further, the
      solute fluorescence spectrum is a function of the solute position in the
      hydrophilic pore, but is independent of position in the hydrophobic pore. The
      origins of these results are investigated, including by decomposition of the free
      energy as a function of solute position into the contributing interactions. The
      implications for time-dependent fluorescence (TDF) experiments, used commonly to
      probe solvation dynamics in nanoconfined solvent systems, are considered. The
      possible role of chromophore diffusion in TDF measurements, and chemistry in
      nanoconfined liquids more broadly, is given particular emphasis.

PMID- 22482695
TI  - Motor-language coupling: direct evidence from early Parkinson's disease and
      intracranial cortical recordings.
AB  - Language and action systems are functionally coupled in the brain as demonstrated
      by converging evidence using Functional magnetic resonance imaging (fMRI),
      electroencephalography (EEG), transcranial magnetic stimulation (TMS), and lesion
      studies. In particular, this coupling has been demonstrated using the action
      sentence compatibility effect (ACE) in which motor activity and language
      interact. The ACE task requires participants to listen to sentences that
      described actions typically performed with an open hand (e.g., clapping), a
      closed hand (e.g., hammering), or without any hand action (neutral); and to press
      a large button with either an open hand position or closed hand position
      immediately upon comprehending each sentence. The ACE is defined as a longer
      reaction time (RT) in the action-sentence incompatible conditions than in the
      compatible conditions. Here we investigated direct motor-language coupling in two
      novel and uniquely informative ways. First, we measured the behavioural ACE in
      patients with motor impairment (early Parkinson's disease - EPD), and second, in
      epileptic patients with direct electrocorticography (ECoG) recordings. In
      experiment 1, EPD participants with preserved general cognitive repertoire,
      showed a much diminished ACE relative to non-EPD volunteers. Moreover, a
      correlation between ACE performance and action-verb processing (kissing and
      dancing test - KDT) was observed. Direct cortical recordings (ECoG) in motor and
      language areas (experiment 2) demonstrated simultaneous bidirectional effects:
      motor preparation affected language processing (N400 at left inferior frontal
      gyrus and middle/superior temporal gyrus), and language processing affected
      activity in movement-related areas (motor potential at premotor and M1). Our
      findings show that the ACE paradigm requires ongoing integration of preserved
      motor and language coupling (abolished in EPD) and engages motor-temporal
      cortices in a bidirectional way. In addition, both experiments suggest the
      presence of a motor-language network which is not restricted to somatotopically
      defined brain areas. These results open new pathways in the fields of motor
      diseases, theoretical approaches to language understanding, and models of action
      perception coupling.

PMID- 22482697
TI  - New benchmark for chemical nomenclature software.
AB  - We propose a new, robust benchmark, called Percentage Round Tripping of Canonical
      Isomeric SMILES (%RTCS), for assessing the ability of chemical nomenclature
      software to convert chemical structures to names and chemical names to
      structures. The benchmark is based on a string comparison between canonical
      isomeric SMILES generated from the original structure and the resultant structure
      from round tripping. Using the latest version of the OpenEye chemical
      nomenclature toolkit, Lexichem v2.1.0, we report %RTCS values of over 92% on
      average for a variety of challenging compound collections.

PMID- 22482698
TI  - Evaluation of potential genotoxicity of five food dyes using the somatic mutation
      and recombination test.
AB  - In this study, different concentrations of five food dyes (amaranth, patent blue,
      carminic acid, indigotine and erythrosine) have been evaluated for genotoxicity
      in the Somatic Mutation and Recombination Test (SMART) of Drosophila
      melanogaster. Standard cross was used in the experiment. Larvae including two
      linked recessive wing hair mutations were chronically fed at different
      concentrations of the test compounds in standard Drosophila Instant Medium.
      Feeding ended with pupation of the surviving larvae. Wings of the emerging adult
      flies were scored for the presence of spots of mutant cells which can result from
      either somatic mutation or somatic recombination. For the evaluation of genotoxic
      effects, the frequencies of spots per wing in the treated series were compared to
      the control group, which was distilled water. The present study shows that
      carminic acid and indigotine demonstrated negative results while erythrosine
      demonstrated inconclusive results. In addition 25 mg mL(-1) concentration of
      patent blue and 12.5, 25 and 50 mg mL(-1) concentrations of amaranth demonstrated
      positive results in the SMART.

PMID- 22482699
TI  - Structural evidence of perfluorooctane sulfonate transport by human serum
      albumin.
AB  - Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant and globally
      persistent organic pollutant. PFOS is mainly distributed in blood with a long
      half-life for elimination. PFOS was found mainly bound to human serum albumin
      (HSA) in plasma, the most abundant protein in human blood plasma, which
      transports a variety of endogenous and exogenous ligands. However, the structural
      basis of such binding remains unclear. Here, we report the crystal structure of
      the HSA-PFOS complex and show that PFOS binds to HSA at a molar ratio of 2:1. In
      addition, PFOS binding renders the HSA structure more compact. Our results
      provide a structural mechanism to understand the retention of surfactants in
      human serum.

PMID- 22482700
TI  - Long-term efficacy of infliximab in hidradenitis suppurativa.
AB  - INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic disease with painful,
      inflamed lesions in the apocrine gland-bearing areas of the body and
      unsatisfactory treatment. TNFalpha blockers have been proposed as promising
      treatments, but only few randomized, short-term, small controlled trials have
      been conducted. The aim of this study was to evaluate long-term response of HS
      patients treated with infliximab (IFX). MATERIAL AND METHODS: A long-term,
      prospective study of 10 patients with moderate-severe refractory HS treated with
      IFX was performed, including assessment of therapy safety, disease severity, and
      activity. Previous reports on IFX treatment for HS were reviewed. RESULTS: Lack
      of response was observed in 20% and relapse in 50% of patients, after a median
      period of 37 weeks. The median number of doses administered was 7.5 during 49
      weeks. No life-threatening adverse events were detected. Systematic review of 61
      previously published cases showed lack of response was associated with previous
      surgery, young age at diagnosis, and long time of evolution of the disease.
      CONCLUSIONS: Long-term IFX therapy might be an efficient, well-tolerated, safe
      option for patients with short-time evolution, severe HS. Relapse is common after
      8 months of continuous treatment, especially in patients with more severe disease
      and in those treated with IFX in monotherapy.

PMID- 22482702
TI  - Direct evidence of concurrent solid-solution and two-phase reactions and the
      nonequilibrium structural evolution of LiFePO4.
AB  - Lithium-ion batteries power many portable devices and in the future are likely to
      play a significant role in sustainable-energy systems for transportation and the
      electrical grid. LiFePO(4) is a candidate cathode material for second-generation
      lithium-ion batteries, bringing a high rate capability to this technology.
      LiFePO(4) functions as a cathode where delithiation occurs via either a solid
      solution or a two-phase mechanism, the pathway taken being influenced by sample
      preparation and electrochemical conditions. The details of the delithiation
      pathway and the relationship between the two-phase and solid-solution reactions
      remain controversial. Here we report, using real-time in situ neutron powder
      diffraction, the simultaneous occurrence of solid-solution and two-phase
      reactions after deep discharge in nonequilibrium conditions. This work is an
      example of the experimental investigation of nonequilibrium states in a
      commercially available LiFePO(4) cathode and reveals the concurrent occurrence of
      and transition between the solid-solution and two-phase reactions.

PMID- 22482701
TI  - Effect of the aqueous extract of Senecio biafrae (Oliv. & Hiern) J. Moore on
      sexual maturation of immature female rat.
AB  - BACKGROUND: Senecio biafrae (Asteraceae) is a medicinal plant widely used by
      traditional healers in the western region of Cameroon for the treatment of female
      infertility. This experiment was designed to evaluate the effect of the aqueous
      extract from leaves and stems of S. biafrae (AESb) on the onset of puberty and
      some biochemical and physiological parameters of reproduction in immature Wistar
      female rats. METHODS: Different doses of AESb were daily and orally administered
      to immature female rats (13 animals/group) for 30 days. At the end of the
      treatment period, six animal of each experimental group were sacrificed and their
      body, ovarian, uterus weight; uterine, ovarian protein or cholesterol level as
      well as data on puberty onset recorded. The remaining animals of each group were
      used for the fertility test and some gestational parameters recorded. RESULTS: A
      linear increase in the growth rate of all animals was observed. The body weight
      gain in animals treated at the dose of 8 mg/kg of AESb significantly increased (p
      < 0.05) after 25 days of treatment while those receiving the doses of 32 and 64
      mg/kg presented a significantly low body weight gain starting from the 19th day
      till the end of the treatment period. The ages (days) of animals at vaginal
      opening (VO) was significantly reduced (p < 0.05) in those treated with the doses
      of 32 (41.25 +/- 0.51) and 64 mg/kg (41.42 +/- 0.54) as compared to control
      animals (43.33 +/- 0.73). AESb significantly increased (p < 0.05) the ovarian
      weight and the number of corpora lutea in animals treated with 8 mg/kg as well as
      the uterine weight and protein levels irrespective of the dose. No significant
      effect of the extract on various fertility and gestational parameters was
      registered. CONCLUSION: The overall results of the present study provide evidence
      on the puberty onset induction and ovarian folliculogenesis effect of AESb in
      immature female rat.

PMID- 22482703
TI  - Cytogenetic biomonitoring of peripheral blood and oral mucosa cells from car
      painters.
AB  - The aim of the present study was to comparatively evaluate genomic damage and
      cellular death in exfoliated oral mucosa cells and peripheral blood from car
      painters. A total of 24 car painters and 19 healthy controls (non-exposed
      individuals) were included in this setting. Individuals had epithelial cells from
      cheek mucosa (left and right side) mechanically exfoliated, placed in fixative
      and dropped in clean slides which were checked for the specific nuclear
      phenotypes. A total of 5 MUL from peripheral blood was collected for the single
      cell gel (comet) assay. The results pointed out statistically significant
      differences (p < 0.05) of micronucleated oral mucosa cells from car painters. In
      addition, DNA damage was detected in peripheral blood cells by single cell gel
      (comet) assay. Nevertheless, exposure to car paints did not cause increases other
      nuclear alterations closely related to cytotoxicity such as karrhyorexis,
      pyknosis and karyolysis in buccal mucosa cells. In summary, the results of the
      present study suggest that car painters comprise a high risk group since paints
      can induce genotoxic and mutagenic effects in peripheral blood and oral mucosa
      cells, respectively.

PMID- 22482704
TI  - Self-assembled squalenoylated penicillin bioconjugates: an original approach for
      the treatment of intracellular infections.
AB  - We describe here new nanoparticles based on the bioconjugation of penicillin G to
      squalene in order to overcome severe intracellular infections by pathogen
      bacteria whose mechanism of resistance arises from the poor intracellular
      diffusion of several antibiotics. Two different squalene-penicillin G conjugates
      were synthesized (pH-sensitive and pH-insensitive), and their self-assembly as
      nanoparticles was investigated through morphology and stability studies. These
      nanoparticles had a size of 140 +/- 10 nm (polydispersity index of 0.1) and a
      negative charge, and they did not display any supramolecular organization.
      Furthermore, they were found stable in water and in different culture medium. The
      cellular uptake and localization of these fluorescently labeled nanoparticles
      were explored on the macrophage cell line J774 by flow cytometry and confocal
      microscopy analysis. The squalenoylated nanoparticles were found to be cell
      internalized through clathrin-dependent and -independent endocytic pathways.
      Moreover, they induced an improved intracellular antibacterial activity on the
      facultative intracellular pathogen S. aureus, compared with free penicillin G,
      despite the absence of co-localization between the bacteria and the nanoparticles
      in the cells. This study suggests that the bioconjugation of an antibiotic to a
      squalene template could be a valuable approach for overcoming the antibiotic
      resistance due to intracellular bacterial infections.

PMID- 22482705
TI  - Reductive N-alkylation of nitroarenes: a green approach for the N-alkylation of
      natural products.
AB  - A simple, mild, cost-effective, and green approach for the reductive mono-N
      alkylation of nitroarenes has been developed. HOAc/Zn are utilized as the
      reducing system together with a carbonyl compound as an alkyl source in methanol.
      Excellent yields were obtained with stoichiometric control of mono- over
      dialkylated products. Application to five complex natural products demonstrated
      the practical utility of the method.

PMID- 22482706
TI  - Assemble, replicate, remodel and evade.

PMID- 22482707
TI  - Structure of human adenovirus.
AB  - A detailed structural analysis of the entire human adenovirus capsid has been
      stymied by the complexity and size of this 150 MDa macromolecular complex. Over
      the past 10 years, the steady improvements in viral genome manipulation
      concomitant with advances in crystallographic techniques and data processing
      software has allowed structure determination of this virus by X-ray diffraction
      at 3.5 A resolution. The virus structure revealed the location, folds, and
      interactions of major and minor (cement proteins) on the inner and outer capsid
      surface. This new structural information sheds further light on the process of
      adenovirus capsid assembly and virus-host cell interactions.

PMID- 22482708
TI  - Structure and cell biology of archaeal virus STIV.
AB  - Recent investigations of archaeal viruses have revealed novel features of their
      structures and life cycles when compared to eukaryotic and bacterial viruses, yet
      there are structure-based unifying themes suggesting common ancestral
      relationships among dsDNA viruses in the three kingdoms of life. Sulfolobus
      solfataricus and the infecting virus Sulfolobus turreted icosahedral virus (STIV)
      is one of the well-established model systems to study archaeal virus replication
      and viral-host interactions. Reliable laboratory conditions to propagate STIV and
      available genetic tools allowed structural characterization of the virus and
      viral components that lead to the proposal of common capsid ancestry with PRD1
      (bacteriophage), Adenovirus (eukaryotic virus) and PBCV (chlorellavirus).
      Microarray and proteomics approaches systematically analyzed viral replication
      and the corresponding host responses. Cellular cryo-electron tomography and thin
      section EM studies uncovered the assembly and maturation pathway of STIV and
      revealed dramatic cellular ultra-structure changes upon infection. The viral
      induced pyramid-like protrusions on cell surfaces represent a novel viral release
      mechanism and previously uncharacterized functions in viral replication.

PMID- 22482709
TI  - M2 protein from influenza A: from multiple structures to biophysical and
      functional insights.
AB  - The M2 protein from influenza A is a proton channel as a tetramer, with a single
      transmembrane helix from each monomer lining the pore. Val27 and Trp41 form gates
      at either end of the pore and His37 mediates the shuttling of protons across a
      central barrier between the N-terminal and C-terminal aqueous pore regions.
      Numerous structures of this transmembrane domain and of a longer construct that
      includes an amphipathic helix are now in the Protein Data Bank. Many structural
      differences are apparent from samples obtained in a variety of membrane mimetic
      environments. High-resolution structural results in lipid bilayers have provided
      novel insights into the functional mechanism of the unique HxxxW cluster in the
      M2 proton channel.

PMID- 22482710
TI  - Broadly neutralizing antibodies against influenza virus and prospects for
      universal therapies.
AB  - Vaccines are the gold standard for the control and prevention of infectious
      diseases, but a number of important human diseases remain challenging targets for
      vaccine development. An influenza vaccine that confers broad spectrum, long-term
      protection remains elusive. Several broadly neutralizing antibodies have been
      identified that protect against multiple subtypes of influenza A viruses, and
      crystal structures of several neutralizing antibodies in complex with the major
      influenza surface antigen, hemagglutinin, have revealed at least 3 highly
      conserved epitopes. Our understanding of the molecular details of these antibody
      antigen interactions has suggested new strategies for the rational design of
      improved influenza vaccines, and has inspired the development of new antivirals
      for the treatment of influenza infections.

PMID- 22482711
TI  - TRIM5 structure, HIV-1 capsid recognition, and innate immune signaling.
AB  - TRIM5 is a restriction factor that blocks retrovirus infection soon after the
      virion core enters the cell cytoplasm. Restriction activity is targeted to the
      virion core via recognition of the capsid protein lattice that encases the viral
      genomic RNA. In common with all of the many TRIM family members, TRIM5 has RING,
      B-box, and coiled-coil domains. As an E3 ubiquitin ligase TRIM5 cooperates with
      the heterodimeric E2, UBC13/UEV1A, to activate the TAK1 (MAP3K7) kinase, NF
      kappaB and AP-1 signaling, and the transcription of inflammatory cytokines and
      chemokines. TAK1, UBC13, and UEV1A all contribute to TRIM5-mediated retrovirus
      restriction activity. Interaction of the carboxy-terminal PRYSPRY or cyclophilin
      domains of TRIM5 with the retroviral capsid lattice stimulates the formation of a
      complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and
      host cell signal transduction. Structural and biochemical studies on TRIM5 have
      opened a much needed window on how the innate immune system detects the distinct
      molecular features of HIV-1 and other retroviruses.

PMID- 22482713
TI  - The variety of study in the field of emerging viruses.

PMID- 22482712
TI  - Hiding the evidence: two strategies for innate immune evasion by hemorrhagic
      fever viruses.
AB  - The innate immune system is one of the first lines of defense against invading
      pathogens. Pathogens have, in turn, evolved different strategies to counteract
      these responses. Recent studies have illuminated how the hemorrhagic fever
      viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA
      (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a
      unique bimodal configuration to mask key cellular recognition sites on dsRNA.
      Conversely, the Lassa fever virus nucleoprotein actually digests the dsRNA
      signature. Collectively, these structural and functional studies shed new light
      on the mechanisms of pathogenesis of these viruses and provide new targets for
      therapeutic intervention.

PMID- 22482715
TI  - Reaching the last one per cent: progress and challenges in global polio
      eradication.
AB  - Since its launch in 1988, the World Health Organization's Global Polio
      Eradication Initiative has reduced worldwide polio incidence by >99%. The most
      dramatic progress was achieved up to the year 2000, the original eradication
      target date, but subsequent years have seen only limited progress in preventing
      the last 1% of cases. Recent gains in India and Nigeria have been offset by
      continued endemicity in Pakistan and Afghanistan, and repeated reseeding of wild
      poliovirus into polio-free areas has led to large outbreaks and re-established
      transmission. Although wild poliovirus type 2 was eradicated in 1999 and wild
      poliovirus type 3 may be nearing eradication, the continued emergence of
      circulating vaccine-derived polioviruses, especially type 2, presents ongoing
      challenges to stopping all poliovirus transmission.

PMID- 22482714
TI  - Henipavirus outbreaks to antivirals: the current status of potential
      therapeutics.
AB  - The henipaviruses, Hendra virus and Nipah virus, are classic examples of recently
      emerged viral zoonoses. In a relatively short time since their discoveries in the
      mid and late 1990s, respectively, a great deal of new information has been
      accumulated detailing their biology and certain unique characteristics. Their
      broad species tropism and abilities to cause severe and often fatal respiratory
      and/or neurologic disease in both animals and humans has sparked considerable
      interest in developing effective antiviral strategies to prevent or treat
      henipavirus infection and disease. Here, recent findings on the few most advanced
      henipavirus countermeasures are summarized and discussed.

PMID- 22482716
TI  - Recent advances in the molecular epidemiology and control of human enterovirus 71
      infection.
AB  - Human enterovirus 71 (HEV71) has emerged as an important cause of viral
      encephalitis in the Southeast Asia over the past 15 years. A pattern of increased
      epidemic activity and endemic circulation of HEV71 has been observed since 1997
      and is associated with the regular emergence of new genetic lineages. Although
      the reason for this increase in HEV71 circulation remains unknown, evidence is
      accumulating that recombination events may drive the evolution of new genetic
      lineages. Prevention of HEV71 epidemics is likely to require the development of
      an effective vaccine. Fortunately, several candidate EV71 vaccines have recently
      been reported, several of which have been shown to be effective in animal models
      and commenced clinical trial in 2010. Furthermore, ongoing investigations into
      the molecular basis of HEV71 infection and virulence have pointed the way towards
      novel approaches to live attenuated vaccine development.

PMID- 22482717
TI  - Crimean-Congo hemorrhagic fever virus: new outbreaks, new discoveries.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection described in
      Asia, Africa and Europe. Humans become infected through the bites of ticks, by
      contact with a patient with CCHF during the acute phase of infection, or by
      contact with blood or tissues from viremic livestock. The occurrence of CCHF
      closely approximates the known world distribution of Hyalomma spp. ticks. The
      novel studies of phylogenetic analyses reveal the interesting relations between
      the strains from distant outbreaks. The clinical features show common dramatic
      progress characterized by hemorrhage, myalgia, and fever. Besides the direct
      infection of endothelium, indirect damage by viral or virus mediated host-derived
      soluble factors that cause endothelial activations and dysfunction occur. In
      diagnosis, enzyme linked immunoassay and real-time reverse transcription
      polymerase chain reaction are used. Early diagnosis is critical for the patient
      and potential nosocomial infections. Supportive therapy is the essential part of
      the case management. Ribavirin was suggested as an effective drug in recent
      studies, and it was found to be beneficial. The health care workers are under
      serious risk of transmission of the infection, particularly during the follow-up
      of the patient, with hemorrhages from the nose, mouth, gums, vagina, and
      injection sites.

PMID- 22482718
TI  - A modified three-dose protocol for colonization of the canine urinary tract with
      the asymptomatic bacteriuria Escherichia coli strain 83972.
AB  - Establishment of asymptomatic bacteriuria is a novel alternative to antimicrobial
      therapy for management of recurrent bacterial urinary tract infection in humans
      and may also be useful for dogs if it can be shown that colonization of the
      canine bladder can be achieved. A three-dose protocol for Escherichia coli strain
      83972 inoculation was developed to attempt induction of persistent bacteriuria in
      healthy dogs. A previous study using a single inoculation colonized dogs for no
      longer than 10 days and multi-dose protocols have been used to establish
      persistent bacteriuria in human patients. Three doses of approximately 10(9)E.
      coli 83972 bacteria were introduced into the bladder of eight healthy female dogs
      over 24h via an indwelling sterile urinary catheter. Three additional dogs were
      sham-inoculated. Duration of colonization ranged from 1 to 28 days (median 2
      days) with no discernible reason for the prolonged colonization in one dog. Multi
      dose inoculation of healthy dogs was not obviously superior to our previous use
      of single-dose inoculation apart from one dog remaining colonized for 28 days
      following the three-dose inoculation protocol.

PMID- 22482719
TI  - Differential gene expression and apoptosis markers in presymptomatic scrapie
      affected sheep.
AB  - Neuronal loss is one of the characteristics of scrapie neuropathology. Previous
      analysis of brains from sheep naturally infected with scrapie that were in a
      terminal stage did not detect a clear induction of apoptosis, although molecular
      changes were evidenced. As neuronal death could be occurring early in scrapie, we
      developed a neuropathological and gene expression study of sheep infected with
      scrapie in a presymptomatic stage. The histopathology, immunolabelling of
      PrP(Sc), Bax and activated caspase-3, and the analysis of the expression of 7
      genes involved in the regulation of the mitochondrial pathway of apoptosis were
      investigated in the following 4 central nervous system areas: medulla oblongata,
      diencephalon, frontal cortex and cerebellum. Moreover, TUNEL and NeuN
      immunolabelling was performed in the medulla oblongata. The PrP(Sc)
      immunolabelling in the four areas, as well as a neuropil spongiform change, were
      more evident in the terminal stage than in presymptomatic animals. Cytoplasmic
      Bax immunostaining was observed in the presymptomatic medulla oblongata. In
      contrast to symptomatic animals, the immunostaining was not extended to the
      hypothalamus, indicating the progression of Bax induction during the course of
      the disease. Although neither caspase-3 immunostaining nor the TUNEL technique
      detected neurons with apoptosis, NeuN-immunolabelled cell counting determined
      that presymptomatic animals have already suffered neuronal loss in a lower or
      equal degree than symptomatic animals. Finally, the gene expression profiles
      indicated that the mitochondrial pathway of apoptosis was activated with higher
      intensity in presymptomatic animals than in symptomatic sheep and confirmed the
      implication of genes such as BAX or AIF in the disease.

PMID- 22482721
TI  - Proliferation and metabolism: it's as easy as APC.
AB  - Proliferating cells must generate both ATP and biosynthetic precursors for
      macromolecular synthesis. While proliferative signals have long been known to
      regulate metabolism, Garedew et al. now demonstrate that the proliferation
      apparatus itself, in the form of the ubiquitin ligase anaphase-promoting
      complex/cyclosome (APC/C), directly controls mitochondrial biogenesis,
      morphology, and respiratory activity.

PMID- 22482720
TI  - Pentachlorophenol hydroxylase, a poorly functioning enzyme required for
      degradation of pentachlorophenol by Sphingobium chlorophenolicum.
AB  - Several strains of Sphingobium chlorophenolicum have been isolated from soil that
      was heavily contaminated with pentachlorophenol (PCP), a toxic pesticide
      introduced in the 1930s. S. chlorophenolicum appears to have assembled a poorly
      functioning pathway for degradation of PCP by patching enzymes recruited via two
      independent horizontal gene transfer events into an existing metabolic pathway.
      Flux through the pathway is limited by PCP hydroxylase. PCP hydroxylase is a
      dimeric protein that belongs to the family of flavin-dependent phenol
      hydroxylases. In the presence of NADPH, PCP hydroxylase converts PCP to
      tetrachlorobenzoquinone (TCBQ). The k(cat) for PCP (0.024 s(-1)) is very low,
      suggesting that the enzyme is not well evolved for turnover of this substrate.
      Structure-activity studies reveal that substrate binding and activity are
      enhanced by a low pK(a) for the phenolic proton, increased hydrophobicity, and
      the presence of a substituent ortho to the hydroxyl group of the phenol. PCP
      hydroxylase exhibits substantial uncoupling; the C4a-hydroxyflavin intermediate,
      instead of hydroxylating the substrate, can decompose to produce H(2)O(2) in a
      futile cycle that consumes NADPH. The extent of uncoupling varies from 0 to 100%
      with different substrates. The extent of uncoupling is increased by the presence
      of bulky substituents at position 3, 4, or 5 and decreased by the presence of a
      chlorine in the ortho position. The effectiveness of PCP hydroxylase is
      additionally hindered by its promiscuous activity with tetrachlorohydroquinone
      (TCHQ), a downstream metabolite in the degradation pathway. The conversion of
      TCHQ to TCBQ reverses flux through the pathway. Substantial uncoupling also
      occurs during the reaction with TCHQ.

PMID- 22482722
TI  - Bone cells crosstalk: noncanonical Roring in the Wnt.
AB  - It is well established that canonical Wnt signaling in bone regulates bone mass.
      Much less is known about the role of noncanonical Wnt signaling. Maeda and
      colleagues now report in Nature Medicine that Wnt5a-Ror2 crosstalk between bone
      cells enhances bone resorption, thereby negatively regulating skeletal
      homeostasis (Maeda et al., 2012).

PMID- 22482723
TI  - Alternative mitochondrial fuel extends life span.
AB  - In this issue of Cell Metabolism, Ristow and colleagues (Zarse et al., 2012)
      elucidate a conserved mechanism through which reduced insulin-IGF1 signaling
      activates an AMP-kinase-driven metabolic shift toward oxidative proline
      metabolism. This, in turn, produces an adaptive mitochondrial ROS signal that
      extends worm life span. These findings further bolster the concept of
      mitohormesis as a critical component of conserved aging and longevity pathways.

PMID- 22482724
TI  - Is predisposition to NAFLD and obesity communicable?
AB  - A forthcoming article in Nature reveals that inflammasome deficiency disturbs gut
      microbiota and predisposes to diet-induced obesity and liver disease. The
      aberrant microbiota and its consequences could be transferred by cohousing mutant
      and wild-type mice, suggesting that some aspects of metabolic syndrome can be
      communicable (Henao-Mejia et al., 2012).

PMID- 22482725
TI  - G-protein-coupled receptors in intestinal chemosensation.
AB  - Food intake is detected by the chemical senses of taste and smell and
      subsequently by chemosensory cells in the gastrointestinal tract that link the
      composition of ingested foods to feedback circuits controlling gut
      motility/secretion, appetite, and peripheral nutrient disposal. G-protein-coupled
      receptors responsive to a range of nutrients and other food components have been
      identified, and many are localized to intestinal chemosensory cells, eliciting
      hormonal and neuronal signaling to the brain and periphery. This review examines
      the role of G-protein-coupled receptors as signaling molecules in the gut, with a
      particular focus on pathways relevant to appetite and glucose homeostasis.

PMID- 22482726
TI  - Orchestration of metabolism by macrophages.
AB  - Metabolic adaptation is a key component of macrophage plasticity and
      polarization, instrumental to their function in homeostasis, immunity, and
      inflammation. Macrophage products also impact metabolism, as illustrated by
      obesity-associated pathologies. Defining the mechanisms regulating macrophage
      metabolic activity and orchestration of metabolism by macrophages is crucial to
      pathology and therapeutic intervention.

PMID- 22482727
TI  - The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated
      longevity through regulation of DAF-16/FOXO.
AB  - The life span of Caenorhabditis elegans is controlled by signaling between the
      germline and the soma. Germ cell removal extends life span by triggering the
      activation of the DAF-16/FOXO transcription factor in the intestine. Here we
      analyze microRNA function in C. elegans aging and show that the microRNA mir-71
      functions to mediate the effects of germ cell loss on life span. mir-71 is
      required for the life span extension caused by germline removal, and
      overexpression of mir-71 further extends the life span of animals lacking germ
      cells. mir-71 functions in the nervous system to facilitate the localization and
      transcriptional activity of DAF-16 in the intestine. Our findings reveal a
      microRNA-dependent mechanism of life span regulation by the germline and indicate
      that signaling among the gonad, the nervous system, and the intestine coordinates
      the life span of the entire organism.

PMID- 22482728
TI  - Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L
      proline catabolism to induce a transient ROS signal.
AB  - Impaired insulin and IGF-1 signaling (iIIS) in C. elegans daf-2 mutants extends
      life span more than 2-fold. Constitutively, iIIS increases mitochondrial activity
      and reduces reactive oxygen species (ROS) levels. By contrast, acute impairment
      of daf-2 in adult C. elegans reduces glucose uptake and transiently increases
      ROS. Consistent with the concept of mitohormesis, this ROS signal causes an
      adaptive response by inducing ROS defense enzymes (SOD, catalase), culminating in
      ultimately reduced ROS levels despite increased mitochondrial activity.
      Inhibition of this ROS signal by antioxidants reduces iIIS-mediated longevity by
      up to 60%. Induction of the ROS signal requires AAK-2 (AMPK), while PMK-1 (p38)
      and SKN-1 (NRF-2) are needed for the retrograde response. IIIS upregulates
      mitochondrial L-proline catabolism, and impairment of the latter impairs the life
      span-extending capacity of iIIS while L-proline supplementation extends C.
      elegans life span. Taken together, iIIS promotes L-proline metabolism to generate
      a ROS signal for the adaptive induction of endogenous stress defense to extend
      life span.

PMID- 22482729
TI  - Mitochondrial dynamics, biogenesis, and function are coordinated with the cell
      cycle by APC/C CDH1.
AB  - Cell proliferation is associated with a high rate of aerobic glycolysis, which
      has been widely interpreted as a compensatory mechanism for suppressed
      mitochondrial function, despite reports of high respiration rates. The molecular
      mechanisms that link cell proliferation with mitochondrial metabolism, dynamics,
      and biogenesis remain obscure. Here, we show that proliferation is associated
      with an increase in both glycolysis and respiration, in conjunction with
      mitochondrial fusion and biogenesis. Changes in mitochondrial morphology and mass
      are due to accumulation of OPA1, MFN1, and TFAM, silencing any of which hinders
      cell proliferation. Moreover, the levels of OPA1, MFN1, and TFAM are regulated by
      the ubiquitin ligase APC/C(CDH1), which also controls proteasomal degradation of
      key glycolytic, glutaminolytic, and cell-cycle proteins. Thus, we have identified
      an important component of the molecular mechanism that coordinates cell
      proliferation with activation of the mitochondrial metabolic machinery that
      provides the necessary energy and biosynthetic substrates.

PMID- 22482730
TI  - In vivo identification of bipotential adipocyte progenitors recruited by beta3
      adrenoceptor activation and high-fat feeding.
AB  - Nutritional and pharmacological stimuli can dramatically alter the cellular
      phenotypes in white adipose tissue (WAT). Utilizing genetic lineage tracing
      techniques, we demonstrate that brown adipocytes (BA) that are induced by beta3
      adrenergic receptor activation in abdominal WAT arise from the proliferation and
      differentiation of cells expressing platelet-derived growth factor receptor alpha
      (PDGFRalpha), CD34, and Sca-1 (PDGFRalpha(+) cells). PDGFRalpha(+) cells have a
      unique morphology in which extended processes contact multiple cells in the
      tissue microenvironment. Surprisingly, these cells also give rise to white
      adipocytes (WA) that can comprise up to 25% of total fat cells in abdominal fat
      pads following 8 weeks of high-fat feeding. Isolated PDGFRalpha(+) cells
      differentiated into both BA and WA in vitro and generated WA after
      transplantation in vivo. The identification of PDGFRalpha(+) cells as bipotential
      adipocyte progenitors will enable further investigation of mechanisms that
      promote therapeutic cellular remodeling in adult WAT.

PMID- 22482731
TI  - Wnt signaling activation in adipose progenitors promotes insulin-independent
      muscle glucose uptake.
AB  - Adipose tissues provide circulating nutrients and hormones. We present in vivo
      mouse studies highlighting roles for Wnt signals in both aspects of metabolism.
      beta-catenin activation in PPARgamma-expressing fat progenitors (PBCA) decreased
      fat mass and induced fibrotic replacement of subcutaneous fat specifically. In
      spite of lipodystrophy, PBCA mice did not develop the expected diabetes and
      hepatosteatosis, but rather exhibited improved glucose metabolism and normal
      insulin sensitivity. Glucose uptake was increased in muscle independently of
      insulin, associated with cell-surface translocation of glucose transporters and
      AMPK activation. Ex vivo assays showed these effects were likely secondary to
      blood-borne signals since PBCA sera or conditioned media from PBCA fat
      progenitors enhanced glucose uptake and activated AMPK in muscle cultures. Thus,
      adipose progenitor Wnt activation dissociates lipodystrophy from dysfunctional
      metabolism and highlights a fat-muscle endocrine axis, which may represent a
      potential therapy to lower blood glucose and improve metabolism.

PMID- 22482733
TI  - Films prepared from electrosterically stabilized nanocrystalline cellulose.
AB  - Electrosterically stabilized nanocrystalline cellulose (ENCC) was modified in
      three ways: (1) the hydroxyl groups on C2 and C3 of glucose repeat units of ENCC
      were converted to aldehyde groups by periodate oxidation to various extents; (2)
      the carboxyl groups in the sodium form on ENCC were converted to the acid form by
      treating them with an acid-type ion-exchange resin; and (3) ENCC was cross-linked
      in two different ways by employing adipic dihydrazide as a cross-linker and water
      soluble 1-ethyl-3-[3-(dimethylaminopropyl)] carbodiimide as a carboxyl-activating
      agent. Films were prepared from these modified ENCC suspensions by vacuum
      filtration. The effects of these three modifications on the properties of films
      were investigated by a variety of techniques, including UV-visible spectroscopy,
      a tensile test, thermogravimetric analysis (TGA), the water vapor transmission
      rate (WVTR), and contact angle (CA) studies. On the basis of the results from UV
      spectra, the transmittance of these films was as high as 87%, which shows them to
      be highly transparent. The tensile strength of these films was increased with
      increasing aldehyde content. From TGA and WVTR experiments, cross-linked films
      showed much higher thermal stability and lower water permeability. Furthermore,
      although the original cellulose is hydrophilic, these films also exhibited a
      certain hydrophobic behavior. Films treated by trichloromethylsilane become
      superhydrophobic. The unique characteristics of these transparent films are very
      promising for potential applications in flexible packaging and other high
      technology products.

PMID- 22482732
TI  - Yin Yang 1 deficiency in skeletal muscle protects against rapamycin-induced
      diabetic-like symptoms through activation of insulin/IGF signaling.
AB  - Rapamycin and its derivatives are mTOR inhibitors used in tissue transplantation
      and cancer therapy. A percentage of patients treated with these inhibitors
      develop diabetic-like symptoms, but the molecular mechanisms are unknown. We show
      here that chronic rapamycin treatment in mice led to insulin resistance with
      suppression of insulin/IGF signaling and genes associated within this pathway,
      such as Igf1-2, Irs1-2, and Akt1-3. Importantly, skeletal muscle-specific YY1
      knockout mice were protected from rapamycin-induced diabetic-like symptoms. This
      protection was caused by hyperactivation of insulin/IGF signaling with increased
      gene expression in this cascade that, in contrast to wild-type mice, was not
      suppressed by rapamycin. Mechanistically, rapamycin induced YY1 dephosphorylation
      and recruitment to promoters of insulin/IGF genes, which promoted interaction
      with the polycomb protein-2 corepressor. This was associated with H3K27
      trimethylation leading to decreased gene expression and insulin signaling. These
      results have implications for rapamycin action in human diseases and biological
      processes such as longevity.

PMID- 22482734
TI  - Aptamer-enabled efficient isolation of cancer cells from whole blood using a
      microfluidic device.
AB  - Circulating tumor cells (CTC) in the peripheral blood could provide important
      information for diagnosis of cancer metastasis and monitoring treatment progress.
      However, CTC are extremely rare in the bloodstream, making their detection and
      characterization technically challenging. We report here the development of an
      aptamer-mediated, micropillar-based microfluidic device that is able to
      efficiently isolate tumor cells from unprocessed whole blood. High-affinity
      aptamers were used as an alternative to antibodies for cancer cell isolation. The
      microscope-slide-sized device consists of >59,000 micropillars, which enhanced
      the probability of the interactions between aptamers and target cancer cells. The
      device geometry and the flow rate were investigated and optimized by studying
      their effects on the isolation of target leukemia cells from a cell mixture. The
      device yielded a capture efficiency of ~95% with purity of ~81% at the optimum
      flow rate of 600 nL/s. Further, we exploited the device for isolating colorectal
      tumor cells from unprocessed whole blood; as few as 10 tumor cells were captured
      from 1 mL of whole blood. We also addressed the question of low throughput of a
      typical microfluidic device by processing 1 mL of blood within 28 min. In
      addition, we found that ~93% of the captured cells were viable, making them
      suitable for subsequent molecular and cellular studies.

PMID- 22482735
TI  - Characterization of HIV type 1 envelope sequence among viral isolates circulating
      in the northern region of Colombia, South America.
AB  - To characterize human immunodeficiency virus (HIV-1) strains circulating in the
      Northern region of Colombia in South America, sequences of the viral envelope
      C2V3C3 region were obtained from patients with different high-risk practices.
      Close to 60% of the sequences were predicted to belong to macrophage-tropic
      viruses, according to the positions of acidic amino acids and putative N-linked
      glycosylation sites. This is in agreement with the fact that most of the patients
      were recently diagnosed individuals. Phylogenic analysis then allowed assignment
      of all 35 samples to subtype B viruses. This same subtype was found in previous
      studies carried out in other Colombian regions. This study thus expands previous
      analyses with previously missing data from the Northern region of the country.
      The number and the length of the sequences examined also help to provide a
      clearer picture of the prevailing situation of the present HIV epidemics in this
      country.

PMID- 22482736
TI  - Interaction of hematoporphyrin with lipid membranes.
AB  - Natural or synthetic porphyrins are being used as photosensitizers in
      photodiagnosis (PD) and photodynamic therapy (PDT) of malignancies and some other
      diseases. Understanding the interactions between porphyrins and cell membranes is
      therefore important to rationalize the uptake of photosensitizers and their
      passive transport through cell membranes. In this study, we consider the
      properties of hematoporphyrin (Hp), a well-known photosensitizer for PD and PDT,
      in the presence of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      bilayer that we use as a model system for protein-free cell membranes. For this
      purpose, we employed 200 ns atomic-scale molecular dynamics (MD) simulations for
      five systems containing the neutral (Hp(0)) or the dianionic form (Hp(2-)) of Hp
      and the POPC bilayer. MD simulations allowed one to estimate the position,
      orientation, and dynamics of Hp molecules inside the membrane. The dye molecules
      were found to reside in the phospholipid headgroup area close to the carbonyl
      groups of the POPC acyl chains. Their orientations were dependent on the
      protonation state of two propionic groups. Hp(2-) was found to have a lower
      affinity to enter the membrane than the neutral form. The dianions, being in the
      aqueous phase, formed stable dimers with a strictly determined geometry. Our
      results fully supported the experimental data and provide a more detailed
      molecular-level description of the interactions of photosensitizers with lipid
      membranes. 

PMID- 22482737
TI  - Freely available conformer generation methods: how good are they?
AB  - Conformer generation has important implications in cheminformatics, particularly
      in computational drug discovery where the quality of conformer generation
      software may affect the outcome of a virtual screening exercise. We examine the
      performance of four freely available small molecule conformer generation tools
      (Balloon, Confab, Frog2, and RDKit) alongside a commercial tool (MOE). The aim of
      this study is 3-fold: (i) to identify which tools most accurately reproduce
      experimentally determined structures; (ii) to examine the diversity of the
      generated conformational set; and (iii) to benchmark the computational time
      expended. These aspects were tested using a set of 708 drug-like molecules
      assembled from the OMEGA validation set and the Astex Diverse Set. These
      molecules have varying physicochemical properties and at least one known X-ray
      crystal structure. We found that RDKit and Confab are statistically better than
      other methods at generating low rmsd conformers to the known structure. RDKit is
      particularly suited for less flexible molecules while Confab, with its systematic
      approach, is able to generate conformers which are geometrically closer to the
      experimentally determined structure for molecules with a large number of
      rotatable bonds (>=10). In our tests RDKit also resulted as the second fastest
      method after Frog2. In order to enhance the performance of RDKit, we developed a
      postprocessing algorithm to build a diverse and representative set of conformers
      which also contains a close conformer to the known structure. Our analysis
      indicates that, with postprocessing, RDKit is a valid free alternative to
      commercial, proprietary software.

PMID- 22482738
TI  - Epidemiological and etiological study of foot mycosis in Tunisia.
AB  - BACKGROUND: Tinea pedis and onychomycosis are among the commonest fungal diseases
      in the world. Recently, there has been an increase in the numbers of fungal
      agents implicated in these conditions. OBJECTIVE: To analyze the epidemiology of
      fungal foot diseases and to identify associated etiological factors in
      outpatients attending the Department of Dermatology of Charles Nicolle Hospital
      in Tunis, Tunisia. PATIENTS AND METHODS: One hundred and forty eight patients
      were assessed for the presence of fungal foot diseases during the period between
      January and April 2009. The mean age was 41.5 years (range: 2-87 years) and sex
      ratio was 0.8. A complete dermatological examination was performed on all
      subjects, and specimens of the feet were taken from patients presenting signs of
      tinea pedis or onychomycosis for microscopy and fungal culture. RESULTS: Fungal
      foot infection was suspected in 71 subjects, and the diagnosis was confirmed in
      67 cases (45.3%) by positive microscopy or culture. Older age and family history
      of mycosis were predisposing factors for foot fungal infection. The condition was
      caused by dermatophytes in 57.1% of cases and Candida species in 35.7%.
      Trichophyton rubrum and Candida parapsilosis were the predominant dermatophyte
      and yeast species, respectively.

PMID- 22482739
TI  - [Results of video-assisted thoracoscopic sympathectomy for facial blushing].
AB  - BACKGROUND: Involuntary craniofacial erythema, or blushing, due to autonomic
      dysfunction can be a cause of psychological distress. Although anecdotal reports
      have suggested that pharmacologic treatments or cognitive behavioral therapy can
      be used to treat the condition, no rigorous analyses of their efficacy have been
      reported. OBJECTIVES: To assess the efficacy of video-assisted thoracoscopic
      sympathectomy and to study phobic anxiety and other personality traits in a
      series of patients with involuntary facial blushing. MATERIALS AND METHODS: We
      carried out a retrospective observational study of patients treated with
      bilateral video-assisted thoracoscopic sympathectomy for blushing over a 7-year
      period (2001-2008). All the patients were treated by a dermatologist, a
      psychologist, and a thoracic surgeon and were informed of the predicted outcomes.
      RESULTS: A total of 204 patients with a mean age of 34 years (range, 15-67 years)
      were included; the numbers of males and females were similar. Only 10% had
      unpredicted outcomes; in such cases, either the procedure was insufficiently
      effective or postoperative reflex sweating developed (and was considered serious
      in 2%). There were no deaths and only 1 case of transient Horner syndrome. Video
      assisted thoracotomy was required for pleural symphysis in 1 patient; 5 patients
      developed pneumothorax, but only 1 of them required pleural drainage.
      CONCLUSIONS: Video-assisted sympathectomy is a safe, effective and definitive
      treatment for disabling blushing. Anxiety that is detected before surgery is a
      reaction to blushing rather than a cause of it.

PMID- 22482740
TI  - [Refractory subacute cutaneous lupus erythematosus treated with rituximab].

PMID- 22482741
TI  - Dermatofibrosarcoma Protuberans in Childhood.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of
      intermediate malignancy that is very rare in childhood. Only 6% of these tumors
      present in children. Clinical diagnosis is very difficult in the early stages of
      disease, but to ensure appropriate treatment it is important to identify DFSP as
      early as possible and rule out benign conditions that are more common at this
      age. The clinical presentation and histopathologic and molecular characteristics
      of DFSP are similar in children and adults. Clinical diagnosis is, however, more
      difficult in children and requires a high degree of suspicion. The absence of
      characteristic features and the rarity of this tumor explain why diagnosis is
      often delayed. Complete surgical excision of the tumor is very important to
      reduce the risk of recurrence. This article presents a review of current
      knowledge about the management of DFSP in children and examines the latest
      treatment options.

PMID- 22482742
TI  - The use of smartphones in general and internal medicine units: a boon or a bane
      to the promotion of interprofessional collaboration?
AB  - Effective communication and coordination are critical components for improving
      collaborative care delivery among different healthcare providers who work in
      mobile and time-pressured environments. Increasingly, healthcare providers are
      exploring alternative communication technologies to help bridge the temporal and
      spatial issues that are often inherent in the clinical communication conundrum.
      Our study examined perceptions of General Internal Medicine (GIM) staff on the
      usage of Smartphone devices and a Webpaging system, which were implemented on the
      inpatient GIM units at two teaching hospitals in North America. An exploratory
      case study approach was employed and in-depth interviews with 31 clinicians were
      conducted. This data-set serves as a subset and prelude to a larger research
      study that examined and compared the impacts of different types of communication
      technologies used in five teaching hospitals. Findings from our study indicate
      that the use of Smartphone technology was well received among clinicians.
      Specifically, healthcare professionals valued the use of emails when
      communicating nonurgent issues and the availability of the phone function that
      enabled access to clinicians especially in urgent situations. Dissatisfaction,
      however, was expressed over the suitability of these smartphone features in
      different communication contexts as well as discrepancies between clinicians over
      the appropriate use of the communication modes. Future interventions in
      communication technology should take into considerations how communication
      mediums and situational contexts (e.g. urgent and nonurgent patient issues)
      impact interprofessional interactions.

PMID- 22482743
TI  - Temporal profiling of human urine VOCs and its potential role under the ruins of
      collapsed buildings.
AB  - CONTEXT: The scent profile of human urine was investigated as potential source of
      chemical markers of human presence in collapsed buildings after natural or man
      made disasters. OBJECTIVE: The main goals of this study were to build a library
      of potential biomarkers of human urine to be used for the detection of entrapped
      victims and to further examine their evolution profile in time. MATERIALS AND
      METHODS: Headspace solid-phase microextraction-gas chromatography-mass
      spectrometry (HS-SPME-GC-MS) was used to detect and identify the volatile organic
      compounds (VOCs) spontaneously released from urine of 20 healthy volunteers.
      Additionally, the evolution of human urine headspace during four days storage at
      room temperature was investigated. RESULTS: 33 omnipresent species with incidence
      higher than 80% were selected as potential urine markers. The most represented
      chemical classes were ketones with 10 representatives, aldehydes (7 species) and
      sulfur compounds (7 species). The monitoring of the evolution of the urine scent
      demonstrated an increase in the emission of 26 omnipresent urinary volatiles
      (rise from 36% to 526%). The highest increase was noted for dimethyldisulfide and
      dimethyltrisulfide (fivefold increase) and 3-methyl-2-butanone, 4-methyl-2
      pentanone and 3-hexanone (fourfold rise). Only three compounds exhibited
      decreasing trend; dimethylsulfone, octanal and propanal. CONCLUSION: The
      ubiquitous urine VOCs identified within this study create a library of potential
      markers of human urine to be verified in further field studies, involving
      portable and sensitive instruments, directly applied in the field.

PMID- 22482744
TI  - Greater striatal dopamine transporter density may be associated with major
      depressive episode.
AB  - BACKGROUND: We examined striatal dopamine transporter (DAT) distribution volume
      ratio (DVR) values in subjects with unipolar or bipolar major depressive episode
      (versus non-depressed healthy volunteers) using the selective DAT radioligand
      [(99m)Tc]TRODAT-1 and single photon emission computed tomography (SPECT). We
      hypothesized that striatal DVR values would be greater in depressed versus non
      depressed subjects, and that greater DVR values may represent a possible clinical
      biomarker of depression. METHODS: [(99m)Tc]TRODAT-1 spect images were acquired
      from 39 depressed and 103 non-depressed drug-free subjects. The primary outcome
      measure was the DVR value of [(99m)Tc]TRODAT-1 binding for the putamen region and
      the combined putamen plus caudate region. RESULTS: DVR values were significantly
      correlated across all striatal regions within both subject groups (p<0.005).
      Depressed subjects had significantly greater DVR values (versus non-depressed
      subjects) in the putamen (p<0.0005) and the combined putamen plus caudate
      (p<0.0005) regions. There was no difference in DVR values between unipolar (n=24)
      and bipolar (n=15) depressed subjects, and no difference in DVR values for
      depressed subjects with or without prior antidepressant exposure. The predictive
      probability of the putamen or combined putamen plus caudate DVR value to
      distinguish depressed from non-depressed subjects was significant (p<0.0005).
      LIMITATIONS: DAT values could potentially be influenced by age, gender,
      diagnosis, prior psychotropic dug exposure, illness length, or symptom severity.
      CONCLUSION: Results confirm prior observations of greater striatal DAT density in
      depressed versus non-depressed subjects, and suggest that greater DVR values may
      possibly represent a potential diagnostic biomarker for distinguish depressed
      from non-depressed individuals.

PMID- 22482745
TI  - Ultrahigh sensitive piezotronic strain sensors based on a ZnSnO3
      nanowire/microwire.
AB  - We demonstrated a flexible strain sensor based on ZnSnO(3) nanowires/microwires
      for the first time. High-resolution transmission electron microscopy indicates
      that the ZnSnO(3) belongs to a rhombohedral structure with an R3c space group and
      is grown along the [001] axis. On the basis of our experimental observation and
      theoretical calculation, the characteristic I-V curves of ZnSnO(3) revealed that
      our strain sensors had ultrahigh sensitivity, which is attributed to the
      piezopotential-modulated change in Schottky barrier height (SBH), that is, the
      piezotronic effect. The on/off ratio of our device is ~587, and a gauge factor of
      3740 has been demonstrated, which is 19 times higher than that of Si and three
      times higher than those of carbon nanotubes and ZnO nanowires.

PMID- 22482746
TI  - Increased nuchal translucency and congenital heart disease.
AB  - Sonographic assessment of fetal nuchal translucency (NT) thickness is the
      cornerstone of screening for chromosomal abnormality at 11-13(+6) weeks
      gestation. This marker was first recognized in pregnancies being karyotyped for
      advanced maternal age, but its underlying pathophysiology remains to be fully
      determined. Although increased NT is clearly associated with changes in both
      lymphatic and cardiac development, neither is an obvious causative agent. The
      association with cardiac defects has now being subjected to a significant amount
      of research, with a large body of evidence showing that this marker is also a
      screening tool for major cardiac defects - although it performs more modestly
      than for chromosomal abnormality. The field continues to change rapidly. Recent
      evidence that uses a combination of increased NT, tricuspid regurgitation and
      abnormal flow in the 'a' wave of the ductus venosus can provide an effective
      screening strategy to predict many major cardiac defects at this early stage of
      pregnancy.

PMID- 22482747
TI  - Relationship between treatment-seeking behaviour and artemisinin drug quality in
      Ghana.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) is currently the
      recommended first-line treatment for uncomplicated malaria infections. However, a
      significant proportion of ACT is assumed to be of poor quality, particularly in
      Africa. In addition, little is known about how treatment-seeking behaviour of
      individuals or drug price is associated with drug quality. METHODS: Caregivers of
      children less than 5 years of age were interviewed on their knowledge of malaria
      and their choices for treatment. Artemisinin drugs were then purchased from
      sellers that caregivers preferred or had previously patronized. The active
      ingredients were quantified by nuclear magnetic resonance spectroscopy. RESULTS:
      A negative relationship was anticipated between the education level of caregivers
      and the quality of anti-malarial drugs purchased. However, of the 33 drugs
      collected from 16 different shops, only one contained less than 80% of its
      purported active ingredient, and most drugs were within 90% of their listed
      amounts. No link was found between drug quality and price. Nonetheless, while ACT
      is the recommended first-line treatment in Ghana, 21% of the drugs collected were
      artemisinin monotherapy, and 27% of the ACT was not co-formulated. Among
      caregivers, higher education was found to be associated with both an increased
      likelihood of seeking treatment in a clinic first, as opposed to visiting drug
      shops or using herbal remedies, and with purchasing drugs from licensed sellers.
      CONCLUSION: Surprisingly, drug quality was found to be uniformly high and thus no
      significant relationship between price, treatment-seeking behaviour and the
      content of the active ingredients was observed. However, artemisinin monotherapy,
      which the WHO considers inappropriate therapy, was still widely available in
      Ghana in 2010. Monotherapy was more likely to be available in unlicensed vendors
      where less-educated caregivers generally shopped. This linkage between education,
      treatment-seeking behaviour and drug availability suggests that the global
      subsidy to reduce the cost of co-formulated ACT can play a significant role in
      increasing its availability.

PMID- 22482748
TI  - Modifications in perfringolysin O domain 4 alter the cholesterol concentration
      threshold required for binding.
AB  - Changes in the cholesterol content of cell membranes affect many physiological
      and pathological events, including the formation of arterial plaques, the entry
      of virus into cells, and receptor organization. Measuring the trafficking and
      distribution of cholesterol is essential to understanding how cells regulate
      sterol levels in membranes. Perfringolysin O (PFO) is a cytolysin secreted by
      Clostridium perfringens that requires cholesterol in the target membrane for
      binding. The specificity of PFO for high levels of cholesterol makes the toxin an
      attractive tool for studying the distribution and trafficking of cholesterol in
      cells. However, the use of the native toxin is limited given that binding is
      triggered only above a determined cholesterol concentration. To this end, we have
      identified mutations in PFO that altered the threshold for how much cholesterol
      is required to trigger binding. The cholesterol threshold among different PFO
      derivatives varied up to 10 mol % sterol, and these variations were not dependent
      on the lipid composition of the membrane. We characterized the binding of these
      PFO derivatives on murine macrophage-like cells whose cholesterol content was
      reduced or augmented. Our findings revealed that engineered PFO derivatives
      differentially associated with these cells in response to changes in cholesterol
      levels in the plasma membrane.

PMID- 22482749
TI  - Surface-bound molecular rulers for probing the electrical double layer.
AB  - Herein, we report the first experimental investigation on the effect of varying
      the position of redox-active moieties, within the electrical double layer, on the
      apparent formal potential and on the electron transfer rate constant. This was
      achieved using a rigid class of molecules, norbornylogous bridges, to place redox
      species (ferrocene) at a fixed position above the surface of the electrode.
      Cyclic voltammetry and alternating current voltammetry were used to calculate the
      apparent formal potential and the electron transfer rate constant for the
      electron transfer between the ferrocene and the gold electrode. We use the effect
      of electric field on the apparent formal potential measurement of the surface
      bound redox species to calculate the potential drop from the initiation of the
      electrical double layer to different distances above it. It was found that self
      assembled monolayers formed from omega-hydroxyalkanethiol have a potential
      profile very similar to that described by classical theories for bare metal
      electrodes. A steep drop in potential in the Stern layer was observed followed by
      a smaller potential drop in the Gouy-Chapman layer. The electron transfer rate
      constant was found to decrease as the distance between the ferrocene moiety and
      the initiation of the double layer is increased. Thus, the electron transfer rate
      constant appears to be dependent on ion concentration.

PMID- 22482750
TI  - On designing new environments for ageing: an introduction to the special issue on
      the design of environments for ageing.

PMID- 22482751
TI  - Adipose tissue-derived mesenchymal stem cell transplantation promotes hepatic
      regeneration after hepatic ischemia-reperfusion and subsequent hepatectomy in
      rats.
AB  - BACKGROUND: Adipose tissue-derived mesenchymal stem cells (ADSCs) are an
      attractive source for regenerative medicine because they are easily accessible
      through minimally invasive methods. We investigated the efficacy of ADSC
      transplantation on outcome after hepatic ischemia-reperfusion and subsequent
      hepatectomy in rats. METHODS: ADSCs were isolated from subcutaneous adipose
      tissue of rats. After clamping the hepatoduodenal ligament for 15 min, the rats
      were subjected to a 70% partial hepatectomy. After releasing the clamp, 2 * 10(6)
      ADSCs per rat were injected through the penile vein. Phosphate buffered saline
      was injected as a control. The parameters of hepatic regeneration, such as
      hepatic regeneration rate, mitotic index, and anti-proliferating cell nuclear
      antigen levels, were examined. Furthermore, the expression of hepatic
      regeneration-associated proteins and genes in the regenerating liver was
      determined. RESULTS: The hepatic regeneration rate 2 d after hepatectomy was
      significantly greater in the ADSC transplanted group compared with the sham
      group. Mitotic index, anti-proliferating cell nuclear antigen levels, and other
      regeneration-associated proteins in the liver were significantly higher in the
      ADSC transplanted group than the sham group on 1 d after hepatectomy. A number of
      hepatic regeneration-associated genes also were significantly upregulated in the
      ADSC transplanted group. CONCLUSIONS: These results indicate that ADSC
      transplantation may provide beneficial effects in the process of liver
      regeneration after hepatic ischemia-reperfusion and subsequent hepatectomy.

PMID- 22482752
TI  - Interval appendectomy after perforated appendicitis: what are the operative risks
      and luminal patency rates?
AB  - BACKGROUND: The need for interval appendectomy after nonoperative management of a
      perforated appendicitis is being questioned owing to recent studies that
      estimated recurrence rates as low as 5% because of obliteration of the
      appendiceal lumen. We review our experience with interval appendectomy in this
      subset of patients to determine the postoperative outcomes and luminal patency
      rates. METHODS: A retrospective review was conducted of all children treated
      nonoperatively for a perforated appendicitis followed by elective interval
      appendectomy during the past 10 years. The data collected included initial
      hospitalization, convalescence period, perioperative course, and luminal patency
      rates. RESULTS: A total of 128 patients were identified, of whom 55% were male.
      Their mean +/- SD age was 9.1 +/- 4.2 years. The mean interval from the initial
      presentation to appendectomy was 65.9 +/- 20.3 d. All but 2 of the patients
      underwent laparoscopic appendectomy with 3 conversions to open surgery. The mean
      operative time was 43.6 +/- 19.2 min. The complication rate was 9%, including 1
      postoperative abscess, 1 reoperation for bleeding, and 1 readmission for
      Clostridium difficile infection. Six patients had a superficial wound infection,
      and 2 patients underwent outpatient procedures for suture granuloma. No risk
      factors for complications were identified. Of the specimens, 16% had obliterated
      lumens. CONCLUSIONS: Major postoperative morbidity for interval appendectomy
      after a perforated appendicitis is low and should not be a deterrent in offering
      interval appendectomy to this subset of patients.

PMID- 22482753
TI  - Evidence for tumor cell spread during local hepatic ablation of colorectal liver
      metastases.
AB  - INTRODUCTION: The aim of the present study was to analyze the impact of
      cryosurgery (CRYO) on liver metastases compared to other thermoablative
      techniques. In a rat liver metastases model, evidence for tumor cell spread was
      analyzed comparing CRYO, radiofrequency ablation (RFA), and laser-induced
      thermotherapy (LITT). METHODS: In an experimental study, we compared cell
      spillage in the washout of isolated perfused rat livers undergoing thermal
      ablation. Within the same model, CC531-GFP rat liver tumors were treated with
      CRYO, RFA, or LITT and the number of vital tumor cells within the perfusate was
      measured. Matrix metalloproteinases (MMP-2, MMP-9) were analyzed after in vivo
      ablation of rat colorectal liver metastases in the third experimental model.
      RESULTS: Our data showed pronounced washout of cells after CRYO with a higher
      amount of intravascular cells and cell detritus compared to RFA and LITT. Only
      the effluent fluid of cryosurgery-treated livers revealed GFP-stained tumor
      cells. MMP-2 and MMP-9 expression was significantly higher after cryosurgery than
      after RFA and LITT. CONCLUSION: When using thermoablative techniques,
      intravascular metastatic cell spillage is highest in CRYO, and increased
      expression of matrix metalloproteinases may further facilitate tumor cell spread.
      Therefore, RFA and LITT may be preferable whenever surgical resection of liver
      tumors is impossible.

PMID- 22482754
TI  - Activated leukocyte cell adhesion molecule (CD166)--its prognostic power for
      colorectal cancer patients.
AB  - BACKGROUND: The activated leukocyte cell adhesion molecule (ALCAM, CD166) has
      been reported to be involved in tumorigenesis of colorectal cancer (CRC) and to
      function as a cancer stem cell marker. Controversial data exist regarding the
      prognostic power of ALCAM expression in CRC. Here, we evaluate the expression of
      ALCAM in a cohort of CRC patients and its usage as a prognostic marker for
      survival. MATERIALS AND METHODS: Tissue specimens from 299 patients with CRC
      treated between 1993 and 2006 were analyzed via ALCAM immunohistochemistry (clone
      MOG/07) using a tissue microarray. Results were correlated with clinical,
      histopathological, and patient survival data (Chi-square test, Kaplan-Meier
      analysis, and log-rank test, respectively). Multivariate analysis also was
      performed (Cox regression). RESULTS: ALCAM is expressed in most primary (76%) and
      secondary (62%) CRC lesions (P = 0.014). Immunohistochemistry revealed an inverse
      association with tumor grading (P = 0.002) but not with any other clinical or
      histopathological data. Kaplan-Meier survival analysis revealed a significant
      overall survival benefit in the group of ALCAM-positive patients (P = 0.019).
      Multivariate analysis showed that ALCAM is an independent positive prognostic
      marker for overall survival (P = 0.023). CONCLUSIONS: ALCAM expression is a
      positive prognostic marker for overall survival of CRC patients, and its
      detection might help to optimize the existing prognostic staging system. Elevated
      expression in higher differentiated tumors might indicate a potential role in the
      early steps of tumorigenesis, and its loss might be associated with reduced
      cellular adhesion, resulting in a higher metastatic potential of the tumor.
      Further studies must be conducted investigating these hypotheses.

PMID- 22482755
TI  - The effects of sorafenib on liver regeneration in a model of partial hepatectomy.
AB  - BACKGROUND: Sorafenib is currently approved for advanced hepatocellular carcinoma
      (HCC) and is presently being studied as an adjuvant treatment for HCC following
      resection. The effects of sorafenib on liver regeneration have not been clearly
      defined. Our objective was to identify the effects of sorafenib on liver
      regeneration in a murine partial hepatectomy (PH) model. MATERIALS AND METHODS:
      We performed PH in C57Bl/6 mice treated with a range of sorafenib doses with
      assessments at several time points. Liver sinusoidal endothelial cells (LSEC) and
      hepatocyte DNA synthesis and proliferation were assessed with 5-bromo-2'
      deoxyuridine (BrdU) and Ki67 by flow cytometry and immunohistochemistry. RESULTS:
      Treatment with sorafenib did not result in any deaths following PH. When we
      measured BrdU uptake to assess DNA synthesis, there was a statistically
      significant increase at 48 h post-PH for nonfibrotic LSEC following treatment
      with 60 mg/kg of sorafenib. However, BrdU and Ki67 staining among LSEC and
      hepatocytes was not significantly affected by sorafenib at any of the other doses
      or time points. BrdU and Ki67 flow cytometry data correlated with
      immunohistochemistry findings and postoperative liver weights. CONCLUSION: In a
      murine PH model, sorafenib did not alter the repair response of normal or
      fibrotic livers following PH as measured by changes in liver weight, DNA
      synthesis, and cellular proliferation. These findings suggest sorafenib
      administered following hepatic resection does not impair liver regeneration.

PMID- 22482756
TI  - In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4'-acetoxy-trans
      stilbene in the treatment of human prostate carcinoma and melanoma.
AB  - BACKGROUND: Resveratrol (RESV) is a naturally occurring compound that may possess
      anticancer capabilities in both prostate carcinoma and melanoma. METHODS: The in
      vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4'-acetoxy-trans
      stilbene (4-ACE) was tested using cellular assays and a xenograft model. Five
      prostate carcinoma cell lines were used for in vitro evaluation. A melanoma cell
      line (Duke melanoma 738 [DM738]) and the prostate carcinoma line CWR22 were used
      for in vivo experiments. Mice were randomized to osmotic mini pumps with 200 MUL
      of RESV (250 mg/mL), 4-ACE (335 mg/mL), or vehicle (50% dimethyl sulfoxide, 50%
      polyethylene glycol). Serum drug and metabolite levels were calculated by high
      performance liquid chromatography with diode-array detection. Western blots were
      performed on treated tumors. Results were analyzed using a student's t-test,
      analysis of variance, and the Mann-Whitney rank sum test. RESULTS: RESV and 4-ACE
      were cytotoxic in a time- and dose-dependent manner in all prostate carcinoma
      cell lines tested. Enhanced growth compared with controls was seen at the 24 h
      time point in four lines treated with RESV and two lines treated with 4-ACE (Ps <
      0.048). In vivo, no difference in either tumor growth or postmortem tumor weight
      was detected in either DM738 (P = 0.555, P = 0.562) or CWR22 (P = 0.166, P =
      0.811) xenografts treated with either drug. Serum drug levels did not correlate
      with tumor growth rates for any treatment group (all Ps > 0.11). Treated tumors
      demonstrated protein changes by western blot. CONCLUSION: Although in vitro data
      were promising, RESV and 4-ACE have limited potential as single agents in the
      treatment of prostate carcinoma and melanoma.

PMID- 22482757
TI  - Formal quality improvement curriculum and DMAIC method results in
      interdisciplinary collaboration and process improvement in renal transplant
      patients.
AB  - BACKGROUND: Broad-based formal quality improvement curriculum emphasizing Six
      Sigma and the DMAIC approach developed by our institution is required for
      physicians in training. DMAIC methods evaluated the common outcome of
      postoperative hyponatremia, thus resulting in collaboration to prevent
      hyponatremia in the renal transplant population. METHODS: To define postoperative
      hyponatremia in renal transplant recipients, a project charter outlined project
      aims. To measure postoperative hyponatremia, serum sodium at admission and
      immediately postoperative were recorded by retrospective review of renal
      transplant recipient charts from June 29, 2010 to December 31, 2011. An Ishikawa
      diagram was generated to analyze potential causative factors. Interdisciplinary
      collaboration and hospital policy assessment determined necessary improvements to
      prevent hyponatremia. Continuous monitoring in control phase was performed by
      establishing the goal of <10% of transplant recipients with abnormal serum sodium
      annually through quarterly reduction of hyponatremia by 30% to reach this goal.
      RESULTS: Of 54 transplant recipients, postoperative hyponatremia occurred in
      92.6% of patients. These potential causes were evaluated: 1) Hemodialysis was
      more common than peritoneal dialysis. 2) Alemtuzumab induction was more common
      than antithymocyte globulin. 3) A primary diagnosis of diabetes existed in 16
      patients (30%). 4) Strikingly, 51 patients received 0.45% sodium chloride
      intraoperatively, suggesting this as the most likely cause of postoperative
      hyponatremia. A hospital policy change to administer 0.9% sodium chloride during
      renal transplantation resulted in normal serum sodium levels postoperatively in
      59 of 64 patients (92.2%). CONCLUSION: The DMAIC approach and formal quality
      curriculum for trainees addresses core competencies by providing a framework for
      problem solving, interdisciplinary collaboration, and process improvement.

PMID- 22482758
TI  - Differentiation of adipose-derived stem cells promotes regeneration of smooth
      muscle for ureteral tissue engineering.
AB  - BACKGROUND: The purpose of the present study was to assess the differentiation
      potential of adipose-derived stem cells (ASCs) into smooth muscle cells (SMCs)
      and their potential for promoting regeneration of smooth muscle for ureteral
      tissue engineering. METHODS: ASCs were isolated, proliferated, and identified in
      vitro. SMC differentiation was induced using SMC induction medium. Gene
      expression was evaluated by quantitative polymerase chain reaction,
      immunofluorescence, and Western blotting. Vessel extracellular matrix was
      obtained by a decellularization process. The induced cells were seeded onto
      vessel extracellular matrix for ureter reconstitution. Grafts were obtained for
      evolutionary histologic studies. Renal function and ureteral patency was
      evaluated by intravenous urography at 16 wk. RESULTS: Flow cytometry demonstrated
      that the ASCs expressed CD90, but did not express CD45 or CD34. After 6 wk of
      induction, upregulation of alpha-smooth muscle actin expression was determined by
      quantitative polymerase chain reaction, and smooth muscle myosin heavy chain
      expression was confirmed by immunofluorescence and Western blotting in the
      induced cells. Vessel extracellular matrix exhibited a nontoxic and bioactive
      effect on the induced cells. Histologically, stratified urothelium and organized
      muscle bundles were observed in the grafts at 16 wk. Intravenous urography
      demonstrated no ureteral stricture or hydroureteronephrosis. CONCLUSIONS: These
      results have demonstrated that ASCs can be differentiated into SMCs and this
      potential promoted smooth muscle regeneration for ureteral tissue engineering.

PMID- 22482759
TI  - Novel biodegradable powder for preventing postoperative pleural adhesion.
AB  - OBJECTIVES: Progress in medical technology and improvements in prognosis have led
      to an increase in polysurgery. However, postoperative pleural adhesion leads to
      poor visualization, bleeding, and lung and vascular trauma during subsequent
      surgeries. To date, there have been no appropriate anti-adhesive agents to
      prevent pleural adhesion. The aim of this study was to investigate the anti
      adhesive effects of commercially available anti-adhesive agents and a newly
      developed powder-type anti-adhesive agent. METHODS: In 48 male rats, we performed
      thoracotomy at the fifth intercostal space. We randomized animals into four
      groups: normal saline, Seprafilm, Interceed, and aldehyde dextran and epsilon
      poly(L-lysine) powder (D-L powder). W killed animals on Day 7 or 28 to evaluate
      the severity, length, gross appearance, and pathological appearance of adhesion
      formation. RESULTS: Adhesion length in the D-L powder group was significantly
      shorter than in the control group (P < 0.05) on both Days 7 and 28.
      Pathologically, all anti-adhesive materials remained on the lung surface on Day
      7. On Day 28, only Interceed remained on the lung surface, in which small vessels
      were present. We also demonstrated the usage of D-L powder during video-assisted
      thoracic surgery in pigs, and found it easy to administer via the trocar sleeve.
      CONCLUSIONS: We found D-L powder to be effective for preventing postoperative
      pleural adhesion, although Seprafilm and Interceed are also somewhat effective.
      However, D-L powder is easier to administer during video-assisted thoracic
      surgery.

PMID- 22482760
TI  - Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning
      in the rat heart in vivo: roles of glycogen synthase kinase-3beta and its
      upstream pathways.
AB  - BACKGROUND: We measured the cardioprotection afforded by sevoflurane
      postconditioning in streptozotocin-induced diabetic rats (DRs) and determined the
      roles of glycogen synthase kinase (GSK), phosphatidylinositol-3-kinase/Akt, and
      extracellular signal-regulated kinase (ERK1/2) in such a procedure. METHODS: DRs
      and nondiabetic rats (NDRs) were subjected to a 30-min coronary artery occlusion
      followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of
      1 minimum alveolar concentration sevoflurane at the first 5 min of reperfusion.
      The infarct size was determined by triphenyltetrazolium chloride staining.
      Expressions of GSK-3beta, Akt, and ERK1/2 were measured using Western blotting.
      RESULTS: In NDRs, the infarct size was significantly decreased from 53.4% +/-
      7.6% to 34.9% +/- 5.6% by sevoflurane postconditioning (P < 0.01). Such an anti
      infarct effect was abolished completely in the DRs, as evidenced by a similar
      infarct size observed between the sevoflurane-treated and untreated DRs (49.3% +/
      8.6% and 49.6% +/- 9.3%, respectively, P > 0.05). Direct inhibition of GSK-3beta
      by injection of SB216763 just before the start of reperfusion induced equivalent
      infarct-sparing effects in both NDRs (37.8% +/- 3.9% and 53.4% +/- 7.6% in
      SB216763-treated and untreated NDRs, respectively; P < 0.01) and DRs (38.8% +/-
      3.2% and 49.3% +/- 8.6% in SB216763-treated and untreated DRs, respectively; P <
      0.05). Sevoflurane postconditioning remarkably enhanced the phosphorylation of
      GSK-3beta Ser(9), Akt Ser(473), and ERK1/2 in NDRs, which were blocked in DRs.
      CONCLUSIONS: The cardioprotection induced by sevoflurane postconditioning is
      abolished by diabetes. This might be due to the impairment of phosphorylation of
      GSK-3beta and its upstream signaling pathways of phosphatidylinositol-3
      kinase/Akt and ERK1/2 in the presence of diabetes.

PMID- 22482761
TI  - Multifaceted effects of rapamycin on functional recovery after spinal cord injury
      in rats through autophagy promotion, anti-inflammation, and neuroprotection.
AB  - BACKGROUND: Spinal cord injuries (SCIs) are serious and debilitating health
      problems that lead to severe and permanent neurological deficits resulting from
      the primary mechanical impact followed by secondary tissue injury. During the
      acute stage after an SCI, the expression of autophagy and inflammatory responses
      contribute to the development of secondary injury. In the present study, we
      examined the multifaceted effects of rapamycin on outcomes of rats after an SCI.
      MATERIALS AND METHODS: We used 72 female Sprague-Dawley rats for this study. In
      the SCI group, we performed a laminectomy at T10, followed by impact-contusion of
      the spinal cord. In the control group, we performed only a laminectomy without
      contusion. We evaluated the effects of rapamycin using the Basso, Beattie, and
      Bresnahan scale for functional outcomes, Western blot analyses for analyzing LC3
      II, tumor necrosis factor expression, and p70S6K phosphorylation, and an
      immunostaining technique for localization and enumeration of microglial and
      neuronal cells. RESULTS: Basso, Beattie, and Bresnahan scores after injury
      significantly improved in the rapamycin-treated group compared with the vehicle
      group (on Day 28 after the SCI; P < .05). The Western blot analysis demonstrated
      that rapamycin enhanced LC3-II expression and decreased p70S6K phosphorylation
      compared with the vehicle (P < .01), which implies promotion of autophagy through
      mammalian target of rapamycin inhibition. Furthermore, rapamycin treatment
      significantly attenuated tumor necrosis factor production and microglial
      expression (P < .05). Immunohistochemistry of NeuN (antibodies specific to
      neurons) showed remarkable neuronal cell preservation in the rapamycin-treated
      group compared with the vehicle-treated group (P < .05), which suggests a
      neuroprotective effect of rapamycin. CONCLUSIONS: Rapamycin is a novel
      neuroprotectant with multifaceted effects on the rat spinal cord after injury.
      Use of such a clinically established drug could facilitate early clinical trials
      in selected cases of human SCIs.

PMID- 22482762
TI  - Mimicry of human sepsis in a rat model--prospects and limitations.
AB  - BACKGROUND: Sepsis and systemic inflammatory response syndrome (SIRS) continue to
      represent critical conditions with persistently high mortality and continue to
      need experimental and clinical research. We developed a rat model of gram
      positive and gram-negative SIRS/sepsis with in vivo visualization of the
      pulmonary microcirculation to evaluate the optimal dosage and application path
      for SIRS/sepsis-inducing agents. METHODS: Male Sprague-Dawley rats (n = 8 per
      group) were assigned to control, lipopolysaccharide (LPS), alphatoxin, or living
      Staphylococcus aureus (strain 68/50) groups. SIRS/sepsis was induced by
      intraperitoneal injection of the differing agents. The onset of SIRS was
      determined through human sepsis parameters and fluorescence video microscopy
      based measurement of platelet and leukocyte velocity within the pulmonary
      vascular system (injection of 5 * 10(6) calcein AM-labeled nonactivated
      platelets; leukocytes labeled in vivo by rhodamine). RESULTS: The optimal dosage
      to induce SIRS was 30 mg/250 g body weight for LPS (bolus injection) and 60
      MUg/250 g body weight for alphatoxin (2 h continuous perfusion). Sepsis was not
      achieved by injection of living S. aureus. The onset of SIRS was seen after 2-5 h
      for LPS and after 2-4 h for alphatoxin after intraperitoneal administration with
      a significantly increased heart rate, breathing rate, and body temperature (P <
      0.05) and significantly decreased cell velocity (P < 0.05). CONCLUSION: Our study
      represents an effective approach for a gram-negative (LPS) and gram-positive
      (alphatoxin) SIRS model to mimic human sepsis. Human sepsis-based criteria were
      used to define SIRS in our rats to achieve an optimal analogy for the human
      system. In our model, higher dosages were needed for SIRS induction than have
      been previously reported. The resulting, considerable heterogeneity of current
      SIRS-inducing models suggests that additional studies in this field are required
      to define standard procedures.

PMID- 22482763
TI  - Gangrenous appendicitis in children: a prospective evaluation of definition,
      bacteriology, histopathology, and outcomes.
AB  - INTRODUCTION: The definition and treatment of gangrenous appendicitis are not
      agreed upon. We performed a prospective study in children to evaluate an
      objective definition of gangrenous appendicitis, as well as associated
      bacteriology, histopathology, and outcomes. METHODS: Five staff pediatric
      surgeons prospectively enrolled patients in the study at the time of appendectomy
      if the following five criteria were met: gray or black discoloration of the
      appendiceal wall; absence of fecalith outside the appendix; absence of visible
      hole in the appendix; absence of gross purulence or fibrinous exudate remote from
      the appendix; and absence of intraoperative appendiceal leak. Peritoneal fluid
      was cultured, and a standard histopathologic review was undertaken. Persistence
      of fever (>37.5 degrees C) and ileus was documented daily. Patients were
      continued postoperatively on ampicillin, gentamicin, and metronidazole until they
      tolerated diet, manifested a 24-h afebrile period, and had a normal leukocyte
      count. Hospital stay, readmissions, and infectious complications were recorded.
      The study took place over a 12-mo period. RESULTS: Thirty-eight patients were
      enrolled, representing 17% of all patients with appendicitis treated during the
      year. Average age was 10.8 +/- 3.5 y. Peritoneal cultures were positive in 53% of
      cases. Gangrene was documented histologically in 61% of specimens. Hospital stay
      was 3.2 +/- 1.1 d. There were no postoperative infectious complications or
      readmissions related to the disease. Neither culture results nor histologic
      gangrene had a statistically significant effect on hospital stay. CONCLUSIONS: An
      objective definition of gangrenous appendicitis is reproducible and has good
      histopathologic association. Recovery from gangrenous appendicitis is not
      influenced by culture or pathology results, and postoperative complications are
      rare. Limiting postoperative antibiotics to 24 h in gangrenous appendicitis may
      significantly decrease the cost of treatment without increasing morbidity.

PMID- 22482764
TI  - Invasive lobular carcinoma predicts micrometastasis in breast cancer.
AB  - BACKGROUND: Invasive lobular carcinomas (ILCs) are almost always estrogen
      receptor (ER) positive. Most delayed breast cancer recurrences occur in ER
      positive patients. Disseminated tumor cells (DTCs) and circulating tumor cells
      (CTCs) have been implicated in recurrence. The purpose of this study was to
      determine whether DTCs and CTCs are associated with ILCs in stage I-III breast
      cancer. MATERIALS AND METHODS: Clinical stage I-III breast cancer patients
      consented to participate in an institutional review board-approved study
      involving collection of bone marrow and blood at surgery for primary breast
      cancer. We assessed DTCs by anti-CK antibody cocktail after cytospin. We detected
      CTCs using CellSearch, and defined them as nucleated cells lacking CD45 but
      expressing cytokeratin. One or more cells per 5 mL bone marrow or 7.5 mL blood
      was considered positive. We performed statistical analyses using chi-square and
      Fisher's exact tests. RESULTS: We prospectively enrolled 422 patients, 64 with
      ILC and 358 with invasive ductal carcinoma. Estrogen receptor positivity was
      higher in ILCs (92.2% versus 66.2%) {P = .001}. We identified DTCs to be 43.4%
      with ILC compared with 28.9% with IDC {P = 0.03}. The CTC rates were similar.
      Either DTCs or CTCs were identified in 75.6% with ILC, compared with 51.7% with
      invasive ductal carcinoma {P = .002}. We observed no correlation between the
      presence of DTCs and CTCs in ILC patients and tumor size, grade, hormone receptor
      status, stage, lymph node status, or administration of NACT. CONCLUSIONS:
      Invasive lobular carcinomas independently predicted micrometastatic disease.
      Because most late recurrences are ER positive, this raises the question of
      whether DTCs and CTCs are indeed responsible for late breast cancer recurrence.

PMID- 22482765
TI  - Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and
      mortality in rats submitted to sepsis by cecal ligation and puncture.
AB  - BACKGROUND: Sepsis is associated with high morbidity and mortality, and survivors
      can present with cognitive dysfunction. The present study was performed to
      investigate the effects of hydrogen-rich saline (HRS) on oxidative stress in the
      brain, cognitive dysfunction, and mortality in a rat model of sepsis. METHODS: A
      rat model of sepsis was induced by cecal ligation and puncture. Physiologic
      saline or HRS was administered intraperitoneally (2.5 mL/kg or 10 mL/kg) 10 min
      before the operation. The survival rate was recorded, and cognitive function was
      tested using the Morris water maze. The reactive oxygen species and
      malondialdehyde levels and superoxide dismutase activity in the hippocampus were
      observed to evaluate the oxidative stress levels. The caspase 3 levels were
      measured to detect apoptosis. The histopathologic changes in the hippocampus were
      evaluated by hematoxylin-eosin staining and the terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick end labeling assay. RESULTS:
      Cecal ligation and puncture resulted in a poor survival rate, evidence of brain
      injury, and cognitive dysfunction. The hippocampal reactive oxygen species and
      malondialdehyde levels increased significantly, and superoxide dismutase activity
      decreased significantly. HRS reversed these changes in a dose-dependent manner.
      CONCLUSIONS: These findings indicate that HRS could attenuate the consequences of
      sepsis induced by cecal ligation and puncture in rats, at least in part, by the
      inhibition of oxidative stress.

PMID- 22482766
TI  - The surgical clerkship: a contemporary paradigm.
AB  - BACKGROUND: Traditional surgical clerkships have been composed of hospitalized
      patients, usually in academic centers, daily resident interaction, periodic
      attending rounds, assigned texts, and a lecture format. However, traditional
      clerkships do not reflect the current changes in learning theory nor the economic
      realities of today's surgical practice. Initiated in 2001, the allopathic Florida
      State University College of Medicine provided an opportunity to create a
      contemporary surgical clerkship. METHODS: At each of 6 regional campuses,
      clerkship students served as apprentices to a board-certified community surgeon.
      In addition, during weekly meetings with the student, a campus-specific Clerkship
      Director administered a centralized curriculum with defined objectives and
      competencies. Contact with residents was minimal, and lectures were not used.
      Students were free to choose from suggested texts or to use alternative learning
      sources. An electronic data system monitored patient contacts. Evaluations of the
      students' clinical performance are 360 degrees. RESULTS: To date, 450 students
      have graduated. No significant differences were found between campuses for the
      following: types of patients encountered, U.S. Medical Liscensure Examination
      Step 2 Clinical Knowledge and Clinical Skills scores, internal Objective
      Structured Clinical Examination results, or National Board of Medical Examiners
      scores (P > 0.05). The national examination metrics have been met or exceeded. On
      the recent anonymous Association of American Medical Colleges Graduation
      Questionnaire survey, the students rated the surgery clerkship as the best course
      in the school. Overall, 23.3% of graduates have chosen some aspect of surgery as
      a career. CONCLUSIONS: A quality clerkship in surgery can be provided using a
      nontraditional community-based system, with as many as 6 distributed campuses.
      Also, the distributed campus model does not lead to inequality in learning
      opportunities, surgical experiences, or basic surgical knowledge. Third,
      documentation of campus comparability is markedly assisted by electronic
      monitoring. Fourth, the tutorial model offers, at the very least, a comparable
      learning experience and is strongly supported by both students and the community
      surgical faculty. Finally, student learning and acquisition of a fund of surgical
      knowledge in this system has been confirmed by national metrics.

PMID- 22482767
TI  - Underuse of curative surgery for early stage upper gastrointestinal cancers in
      the United States.
AB  - BACKGROUND: Surgery is the cornerstone of potentially curative therapy for upper
      gastrointestinal cancer. We analyzed the patterns of treatment regarding the use
      of surgery for early-stage upper gastrointestinal cancer in the United States.
      METHODS: The Surveillance, Epidemiology, and End Research database was used to
      identify patients with cancer of the esophagus, stomach, pancreas, liver,
      gallbladder, biliary tract, or duodenum (2004-2007). Only patients with
      potentially resectable stage I and II disease were selected. The primary outcome
      measure was the use of curative intent surgery. The secondary outcomes were the
      predictors of surgery. RESULTS: We identified 29,249 patients with a median age
      of 69 years. Only 54% of the patients underwent cancer-directed surgical
      resection, ranging from 28% for liver cancer to 89% for gallbladder cancer. The
      remaining patients underwent either local excision (8%) or no surgery (38%).
      Among the no surgery group, most patients (79%) were documented as "not being
      recommended for resection." The independent variables on multivariate analysis
      predictive of a nonoperative approach included black race, age older than 75
      years, tumor size greater than 5 cm, and high poverty level (P < 0.001). Patients
      who did not undergo surgery had worse median and overall survival at 3 years than
      patients undergoing surgery (11 months versus 36 months and 14% versus 43%,
      respectively; P < 0.001). CONCLUSIONS: Almost one half of patients with early
      stage upper gastrointestinal cancer did not receive potentially curative surgery,
      with an adverse effect on overall survival. A combination of demographic, tumor,
      and socioeconomic factors were predictive of a lack of surgical resection.

PMID- 22482768
TI  - y+ cationic amino acid transport of arginine in packed red blood cells.
AB  - BACKGROUND: Transfusion of packed red blood cells (PRBCs) is associated with
      morbidity and mortality. The mechanisms are not fully understood. Packed red
      blood cells deplete extracellular arginine and possess transporters for arginine,
      an amino acid essential for normal immunity. We hypothesize that the membrane y+
      amino acid transporter contributes to arginine depletion in PRBCs. MATERIALS AND
      METHODS: We titrated PRBCs to a 10% hematocrit with phosphate-buffered saline,
      blocked PRBC y+ transporters using n-ethylmaleimide (0.2 mM), and measured
      arginine and ornithine levels using liquid chromatography-mass spectroscopy. We
      added radiolabeled L-arginine [4,5-(3)H] (10 MUmol/L) added to similar culture
      conditions and measured arginine uptake in counts per minute (CPM). We examined
      storage periods of 6-9 d, 1-4 wk, and 6 wk, and correlated donor demographics
      with arginine uptake. RESULTS: n-Ethylmaleimide blockade of y+ transporters
      impaired PRBC arginine depletion from culture media (117.6 +/- 8.6 MUM versus
      76.9 +/- 5.8 MUM; P < 0.001) and reduced intracellular L-arginine (7,574 +/- 955
      CPM versus 18,192 +/- 1,376 CPM; P < 0.01). Arginine depletion increased with
      storage duration (1 wk versus 6 wk; P < 0.002). With n-ethylmaleimide treatment,
      6-wk-old PRBCs preserved more culture arginine (P < 0.008) than at shorter
      durations. Nine-day storage duration increased L-arginine uptake compared with 6-
      to 8-day storage (n = 77, R = 0.225, P < 0.05). Extracellular arginine depletion
      and extracellular ornithine synthesis varied among donors and correlated
      inversely (R = -0.5, P = 0.01). CONCLUSIONS: Membrane y+ transporters are
      responsible for arginine depletion by PRBCs. Membrane y+ activity increases with
      storage duration. Arginine uptake varies among donors. Membrane biology of RBCs
      may have a role in the negative clinical effects associated with PRBC
      transfusion.

PMID- 22482769
TI  - Composite tissue allotransplantation in newborns: a swine model.
AB  - BACKGROUND: Management of congenital limb aplasia or facial malformations could
      be improved by composite tissue allotransplantation (CTA), a technique that has
      never been performed in newborns. For this, however, the induction of donor
      specific tolerance would be mandatory, as long-term immunosuppression is not
      acceptable in this non-lifesaving procedure. Induction of tolerance has been
      shown to be possible in a newborn CTA rat model but has never been tested in
      large-animal models. Our goals were to establish a model of CTA in newborn swine
      to see if tolerance could be obtained without immunosuppression and to assess
      rejection or tolerance properties via clinical and histologic examinations.
      MATERIALS AND METHODS: We applied a CTA heterotopic knee swine model. We
      performed two series of surgical procedures: Series 1 was 20 autografts in 6-day
      old (1-10) 2,544 kg (1,140-4,060 kg) piglets; Series 2 was 10 allografts without
      immunosuppression between outbred animals aged 7.8 d (6-10) and weighing 2,770 kg
      (2,200-3,550 kg). RESULTS: In Series 1, six early deaths and two cases of
      vascular failure were observed. In Series 2, no spontaneous deaths were observed
      and all piglets presented clinical and histologic rejection. CONCLUSIONS: Our
      findings strongly suggest that newborn immunologic status is not sufficient for
      the development of tolerance in large animals without immunologic intervention.
      Complications and animal death after transplantation correlate with age and
      weight. Low rates for both vascular failure and postoperative death permit the
      use of this model in piglets weighing over 2 kg and aged more than 6 d for
      research on newborn CTA.

PMID- 22482770
TI  - Incidence of concomitant hyperparathyroidism in patients with thyroid disease
      requiring surgery.
AB  - BACKGROUND: Thyroid disease and hyperparathyroidism (HPT) are among the most
      common endocrine disorders, however, their association has not been well
      established. The aim of the present study was to determine the incidence of
      concomitant HPT in patients with thyroid disease requiring surgery, because a
      single definitive surgery should ideally be performed. METHODS: We
      retrospectively reviewed a prospectively maintained database of patients who
      underwent thyroidectomy at a single institution. Data collected included the
      patients' initial indication for surgery, preoperative workup, and operative
      findings. RESULTS: Of the 1,049 patients who underwent thyroidectomy, 56 (5%) had
      concomitant HPT and underwent simultaneous parathyroidectomy. Of these 56
      patients, 36 initially presented with thyroid disease and 20 with HPT. The mean
      age was 59 +/- 2 years, and 79% were women. The mean preoperative calcium and
      parathyroid hormone levels were elevated at 10.4 +/- 0.1 mg/dL and 87 +/- 7
      pg/mL, respectively. Most of these patients had primary HPT (n = 54, 96%). Of the
      36 patients presenting initially with thyroid disease, 26 had an elevated calcium
      or parathyroid hormone value and were preoperatively diagnosed with HPT. The
      remaining 10 patients had normal laboratory findings; however, a pathologically
      enlarged parathyroid gland was found at thyroidectomy. The overall cure rate for
      HPT within our series was 96%. CONCLUSION: The incidence of concomitant HPT in
      patients with thyroid disease requiring surgery is significant at 5%. Recognition
      of concurrent disease is important, because it allows for a single definitive
      surgery to treat both pathologies.

PMID- 22482772
TI  - Small bowel fibrosis and systemic inflammatory response after ileocolonic
      anastomosis in IL-10 null mice.
AB  - BACKGROUND: Crohn's disease recurrence after an ileocecal resection is common;
      yet, its pathophysiology is poorly understood and available treatment is
      suboptimal. The purpose of this study was to examine the bacterial, local, and
      systemic immune changes that follow ileocolonic anastomosis in a rodent model of
      Crohn's disease, the interleukin-10 gene-deficient (IL-10 null) mice. MATERIALS
      AND METHODS: We divided wild-type and IL-10 null mice into three treatment
      groups: ileocolonic anastomosis, sham operation (ileo-ileal anastomosis), and
      control group without an operation. We sacrificed mice at 6 and 15 wks after the
      operation. At 6 wks, we assessed bacterial changes using the denaturing gel
      electrophoresis and similarity coefficient calculation. At both time points, we
      examined the small bowel for inflammation and fibrosis with histology. We
      measured the interferon gamma secretion by splenocytes stimulated with
      gastrointestinal bacterial antigens and splenocyte composition as a marker of
      systemic response. RESULTS: At 6 wks, ileocolonic anastomosis resulted in
      increased similarity in bacterial species between the ileum and colon. The
      ileocolonic anastomosis did not lead to significant inflammation in the small
      intestine, but it resulted in an increased collagen deposition in all animals
      undergoing surgery, the most pronounced fibrosis of which was present in IL-10
      null mice 15 wks after ileocolonic anastomosis. Furthermore, this was associated
      with significantly increased interferon gamma secretion by bacterial antigen
      stimulated splenocytes and a decreased number of CD11+ cells in the same
      experimental group. CONCLUSIONS: Ileocolonic anastomosis leads to bacterial
      changes in the terminal ileum. In the genetically susceptible host, it is
      associated with small bowel fibrosis and systemic immune alterations. The
      composition of immune cells in the spleen is altered and splenocytes hypersecrete
      proinflammatory cytokine (interferon gamma) when challenged with gastrointestinal
      bacterial antigens.

PMID- 22482771
TI  - Utilization of lymph node assessment in patients with ductal carcinoma in situ
      treated with lumpectomy.
AB  - BACKGROUND: Lymph node assessment (LNA), including sentinel lymph node biopsy
      (SLNB), is controversial in patients undergoing lumpectomy for ductal carcinoma
      in situ (DCIS). Our goal was to identify factors influencing LNA in these
      patients. METHODS: We used the Surveillance Epidemiology and End Results database
      to identify all female patients treated with lumpectomy for DCIS from 2000 to
      2008. We excluded patients without histologic confirmation, including those
      diagnosed at autopsy, and those for whom LNA status was unknown. Multivariate
      logistic regression models predicted use of LNA. Likelihood of undergoing LNA was
      reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A
      total of 62,935 patients met inclusion criteria. Approximately 15% (N = 9726) had
      regional LNA at the time of lumpectomy, with 12% (N = 7294) undergoing SLNB.
      Factors associated with an increased likelihood of undergoing LNA included
      treatment in the Southeast (OR 1.25, CI 1.04-1.22); treatment after the year
      2000; grade II (OR 2.71, CI 2.48-2.96), III (OR 2.38, CI 2.18-2.59), or IV (OR
      2.61, CI 2.37-2.88) tumors; DCIS size 2-5 cm (OR 1.49, CI 1.37-1.62) or >5 cm (OR
      2.16, CI 1.78-2.61), and estrogen receptor-negative (OR 1.29, CI 1.16-1.43) or
      progesterone receptor-negative (OR 1.22, CI 1.11-1.33) tumors. Factors associated
      with a decreased likelihood of undergoing regional LNA were age >60 (OR 0.83, CI
      0.79-0.87), and Asian race (OR 0.88, CI 0.81-0.96). Factors predictive of LNA in
      general were also predictive of SLNB. CONCLUSIONS: Although LNA is controversial
      for patients undergoing lumpectomy for DCIS, it is used in 15% of cases. Further
      research establishing for the benefit of LNA in DCIS patients treated with
      lumpectomy is needed.

PMID- 22482773
TI  - Characterization of agonist binding to His524 in the estrogen receptor alpha
      ligand binding domain.
AB  - The bioactivities of the natural steroidal estrogen 17beta-estradiol (E2), the
      synthetic estrogen diethylstilbestrol (DES), and the phytoestrogen genistein
      (GEN) are intimately associated with their binding to the estrogen receptor alpha
      ligand binding domain (ERalpha LBD) and accordingly allostery. Molecular modeling
      techniques have been performed on agonists in complex with the LBD, focusing on
      the pivotal role of His524 modeled as the epsilon-tautomer and the protonated
      form (depending on pH). It is found that E2 binds to the active LBD with the aid
      of Leu525, showing existing stable patterns of an H-binding network with Glu419
      via His524 in all models. The main difference seen in the effect is that the full
      agonists E2 and DES have higher binding energies to the protonated His524 than
      the partial agonists GEN and Way-169916 (W), which is in line with noted
      experimental transcriptional activities. In conclusion, the study demonstrates
      that the phytoestrogen GEN interacts differently with the LBD than what E2 and
      DES do, which explains the observed signaling differences. 

PMID- 22482774
TI  - Potential and limitations of ensemble docking.
AB  - A major problem in structure-based virtual screening applications is the
      appropriate selection of a single or even multiple protein structures to be used
      in the virtual screening process. A priori it is unknown which protein
      structure(s) will perform best in a virtual screening experiment. We investigated
      the performance of ensemble docking, as a function of ensemble size, for eight
      targets of pharmaceutical interest. Starting from single protein structure
      docking results, for each ensemble size up to 500,000 combinations of protein
      structures were generated, and, for each ensemble, pose prediction and virtual
      screening results were derived. Comparison of single to multiple protein
      structure results suggests improvements when looking at the performance of the
      worst and the average over all single protein structures to the performance of
      the worst and average over all protein ensembles of size two or greater,
      respectively. We identified several key factors affecting ensemble docking
      performance, including the sampling accuracy of the docking algorithm, the choice
      of the scoring function, and the similarity of database ligands to the
      cocrystallized ligands of ligand-bound protein structures in an ensemble. Due to
      these factors, the prospective selection of optimum ensembles is a challenging
      task, shown by a reassessment of published ensemble selection protocols.

PMID- 22482775
TI  - Size control and catalytic activity of highly dispersed Pd nanoparticles
      supported on porous glass beads.
AB  - This paper presents a novel in situ method to prepare monodispersed palladium
      nanoparticles supported on porous glass beads with an egg-shell structure at room
      temperature. This method integrates two processes of ion exchange and reduction
      in one step just by changing the solvent from water to alcohol. The monodispersed
      Pd nanoparticles around 3.75 nm in diameter with a face-centered cubic structure
      have been successfully prepared. The adsorption capacity for palladium reached
      55.00 +/- 0.55 mg/g in ethanol, which was 26 times larger than that in water.
      These Pd nanoparticles supported on porous glass beads showed an excellent
      catalytic performance through the hydrogenation of cyclohexene. In addition, this
      in situ method was also successfully applied to prepare monodispersed silver and
      gold nanoparticles supported on porous glass beads. Overall, this facile method
      provided an alternative for preparing a supported nanoparticle catalyst in a
      green way.

PMID- 22482776
TI  - Digital polymerase chain reaction in an array of femtoliter polydimethylsiloxane
      microreactors.
AB  - We developed a simple, compact microfluidic device to perform high dynamic-range
      digital polymerase chain reaction (dPCR) in an array of isolated 36-femtoliter
      microreactors. The density of the microreactors exceeded 20000/mm(2). This
      device, made from polydimethylsiloxane (PDMS), allows the samples to be loaded
      into all microreactors simultaneously. The microreactors are completely sealed
      through the deformation of a PDMS membrane. The small volume of the microreactors
      ensures a compact device with high reaction efficiency and low reagent and sample
      consumption. Future potential applications of this platform include multicolor
      dPCR and massively parallel dPCR for next generation sequencing library
      preparation.

PMID- 22482777
TI  - Robot-assisted radical prostatectomy: ready to be counted?

PMID- 22482778
TI  - Comparative analysis of outcomes and costs following open radical cystectomy
      versus robot-assisted laparoscopic radical cystectomy: results from the US
      Nationwide Inpatient Sample.
AB  - BACKGROUND: Although robot-assisted laparoscopic radical cystectomy (RARC) was
      first reported in 2003 and has gained popularity, comparisons with open radical
      cystectomy (ORC) are limited to reports from high-volume referral centers.
      OBJECTIVE: To compare population-based perioperative outcomes and costs of ORC
      and RARC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective observational cohort
      study using the US Nationwide Inpatient Sample to characterize 2009 RARC compared
      with ORC use and outcomes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Propensity score methods were used to compare inpatient morbidity and mortality,
      lengths of stay, and costs. RESULTS AND LIMITATIONS: We identified 1444 ORCs and
      224 RARCs. Women were less likely to undergo RARC than ORC (9.8% compared with
      15.5%, p = 0.048), and 95.7% of RARCs and 73.9% of ORCs were performed at
      teaching hospitals (p<0.001). In adjusted analyses, subjects undergoing RARC
      compared with ORC experienced fewer inpatient complications (49.1% and 63.8%, p =
      0.035) and fewer deaths (0% and 2.5%, p<0.001). RARC compared with ORC was
      associated with lower parenteral nutrition use (6.4% and 13.3%, p = 0.046);
      however, there was no difference in length of stay. RARC compared with ORC was
      $3797 more costly (p = 0.023). Limitations include retrospective design, absence
      of tumor characteristics, and lack of outcomes beyond hospital discharge.
      CONCLUSIONS: RARC is associated with lower parenteral nutrition use and fewer
      inpatient complications and deaths. However, lengths of stay are similar, and the
      robotic approach is significantly more costly.

PMID- 22482779
TI  - Re: Shahrokh F. Shariat, Richard Zigeuner, Michael Rink, et al. Subclassification
      of pT3 urothelial carcinoma of the renal pelvicalyceal system is associated with
      recurrence-free and cancer-specific survival: proposal for a revision of the
      current TNM classification. Eur Urol. In press. DOI:10.1016/j.eururo.2012.01.019.

PMID- 22482780
TI  - What is needed for improved patient care in upper urinary tract urothelial
      carcinoma?

PMID- 22482781
TI  - [Treatment with plasma infusion in a patient suffering hemolytic uremic
      syndrome].

PMID- 22482782
TI  - [Surviving a stroke: is all quiet on the front or the great illusion?].

PMID- 22482783
TI  - Natural background levels and threshold values of chemical species in three large
      scale groundwater bodies in Northern Italy.
AB  - We analyze natural background levels (NBLs) and threshold values (TVs) of
      spatially distributed chemical species (NH(4), B and As) which may be a potential
      pressure and concern in three large scale alluvial and fluvio-deltaic aquifers at
      different depths of the Apennines and Po river plains in Emilia-Romagna, Northern
      Italy. Our results are based on statistical methodologies designed to separate
      the natural and anthropogenic contributions in monitored concentrations by
      modeling the empirical distribution of the detected concentration with a mixture
      of probability density functions. Available chemical observations are taken over
      a 20 years period and are associated with different depths and cover planar
      investigation scales of the order of hundreds of kilometers. High concentration
      values detected for NH(4) and B appear to be related to high natural background
      levels. Due to interaction with the host rock in different geochemical
      environments we observed that concentration vary in time and space (including in
      depth) consistently with the hydrogeochemical features and the occurrence of
      natural attenuation mechanisms in the analyzed reservoirs. Conversely, estimated
      As NBLs are not consistent with the conceptual model of the hydrogeochemical
      behavior of the systems analyzed and experimental evidences of As content in
      aquifer cores. This is due to the inability of these techniques to incorporate
      the complex dynamics of the processes associated with the specific
      hydrogeochemical setting. Statistical analyses performed upon aggregating the
      concentration data according to different time observation windows allow
      identifying temporal dynamics of NBLs and TVs of target compounds within the
      observation time frame. Our results highlight the benefit of a dynamic monitoring
      process and analysis of well demarcated groundwater bodies to update the
      associated NBLs as a function of the temporal dependence of natural processes
      occurring in the subsurface. Monitoring protocols could also include the detailed
      evaluation of the geochemistry (redox) of the aquifers.

PMID- 22482784
TI  - Analysis of procedures for sampling contaminated soil using Gy's Sampling Theory
      and Practice.
AB  - Soil sampling is a critical step in environmental site assessment studies. The
      representativeness of soil samples has a direct influence on financial,
      liability, environmental and public health issues associated with the outcome of
      remediation activities. Representativeness must be quantified for assessing and
      designing soil sampling procedures. Gy's Sampling Theory and Practice (STP) was
      used to analyze the reproducibility of two soil sampling procedures, namely a
      procedure based on grab sampling (GSP) and an alternative procedure (ASP)
      developed from STP principles. Sampling reproducibility, a component of sampling
      representativeness, was determined by theoretical calculations and experimental
      measurement of relative variances in trace metals concentrations at each stage of
      both sampling procedures. The ASP significantly increased the reproducibility of
      soil sampling compared to the GSP. Larger relative variances occurred during
      field sampling for the ASP and during laboratory sampling for the GSP. They were
      due to subsample mass reduction without control over particle size. Relative
      theoretical and experimental variances were in agreement. However, large
      discrepancies were observed for all sampling stages of both procedures between
      absolute theoretical and experimental relative variances. In the case of Pb,
      theoretical calculations were closer to experimental measurements when using a
      calculated value of the liberation factor (l) based on mineralogical data rather
      than l=1. It was shown that the b-exponent had a large influence on theoretical
      variances. Increasing the estimate of b from 0.5 to 1 largely improved the
      agreement between theory and experiment. Finally, 99% of experimental relative
      variance was explained by sampling errors compared to analytical errors.

PMID- 22482785
TI  - Life cycle assessment perspectives on delivering an infant in the US.
AB  - This study introduces life cycle assessment as a tool to analyze one aspect of
      sustainability in healthcare: the birth of a baby. The process life cycle
      assessment case study presented evaluates two common procedures in a hospital, a
      cesarean section and a vaginal birth. This case study was conducted at Magee
      Womens Hospital of the University of Pittsburgh Medical Center, which delivers
      over 10,000 infants per year. The results show that heating, ventilation, and air
      conditioning (HVAC), waste disposal, and the production of the disposable custom
      packs comprise a large percentage of the environmental impacts. Applying the life
      cycle assessment tool to medical procedures allows hospital decision makers to
      target and guide efforts to reduce the environmental impacts of healthcare
      procedures.

PMID- 22482787
TI  - Origin and fate of organic compounds in water: characterization by compound
      specific stable isotope analysis.
AB  - Within the past 15 years, compound-specific stable isotope analysis has continued
      to increase in popularity in the area of contaminant hydrology of organic
      molecules. In particular, in cases where concentration data alone are
      insufficient to elucidate environmental processes unequivocally, the isotope
      signature can provide additional unique information. Specifically, it can help
      answer questions about contaminant source apportionment, quantification of biotic
      and abiotic processes, and identification of transformation reactions on a
      mechanistic level. We review advances in laboratory and field investigations and
      exemplary applications in contaminant hydrology via stable isotope analysis. We
      also highlight future directions in the field.

PMID- 22482788
TI  - Engineered nanoparticles and their identification among natural nanoparticles.
AB  - The more nanotechnology develops, the more likely the release of engineered
      nanoparticles into the environment becomes. Due to a huge excess of natural
      nanoparticles, the identification and quantification of engineered nanoparticles
      pose a big challenge to analysts. Moreover, identification in a qualitative sense
      and quantification by mass concentration alone are not sufficient, because the
      potential environmental hazard arising from engineered nanoparticles is
      controlled by many other properties of the particles. We discuss the most
      important methods of fractionation and detection of both natural and engineered
      nanoparticles, with a focus on the chemical nature of the particles, particle
      concentration, and particle size. Analyses should not rely on only one method;
      instead, several complementary methods should, if possible, be used. Coupled
      techniques should be further developed and increasingly applied. Dedicated
      techniques that are tailored to the search for a particular sort of engineered
      nanoparticles are more promising than universal approaches that search for any
      engineered nanoparticles.

PMID- 22482789
TI  - Modeling selected emulsions and double emulsions as memristive systems.
AB  - The recent development in basic and applied science and engineering of finely
      dispersed systems is presented in general, but more attention has been paid to
      the liquid-liquid finely dispersed systems or to the particular emulsions and
      double emulsions. The selected systems for theoretical and experimental research
      were emulsions and double emulsions that appeared in the pilot plant for
      extraction of uranium from wet phosphoric acid. The objective of this research
      was to try to provide a new or different approach to elaborate the complex
      phenomena that occur at developed liquid-liquid interfaces. New concepts were
      introduced, the first is a concept of an entity, and the corresponding
      classification of finely dispersed systems and the second concept consider the
      introduction of an almost forgotten basic electrodynamics element memristor, and
      the corresponding memristive systems. Based on these concepts a theory of
      electroviscoelasticity was proposed and experimentally corroborated using the
      selected representative liquid-liquid system. Also, it is shown that the droplet,
      and/or droplet-film structure, that is, selected emulsion and/or double emulsion
      may be considered as the particular example of memristive systems.

PMID- 22482786
TI  - Metabolic toxicity screening using electrochemiluminescence arrays coupled with
      enzyme-DNA biocolloid reactors and liquid chromatography-mass spectrometry.
AB  - New chemicals or drugs must be guaranteed safe before they can be marketed.
      Despite widespread use of bioassay panels for toxicity prediction, products that
      are toxic to a subset of the population often are not identified until clinical
      trials. This article reviews new array methodologies based on enzyme/DNA films
      that form and identify DNA-reactive metabolites that are indicators of
      potentially genotoxic species. This molecularly based methodology is designed in
      a rapid screening array that utilizes electrochemiluminescence (ECL) to detect
      metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA
      adducts and metabolites for liquid chromatography-mass spectrometry (LC-MS)
      analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor
      LC-MS approach provides a valuable follow-up on structure, identification, and
      formation rates of DNA adducts for toxicity hits from the ECL array screening.
      Specific examples using this strategy are discussed. Integration of high
      throughput versions of these toxicity-screening methods with existing drug
      toxicity bioassays should allow for better human toxicity prediction as well as
      more informed decision making regarding new chemical and drug candidates.

PMID- 22482790
TI  - Cortisol and interleukin-6 responses during intermittent exercise in two
      different hot environments with equivalent WBGT.
AB  - Blood marker concentrations such as cortisol (COR) and interleukin (IL)-6 are
      commonly used to evaluate the physiological strain associated with work in the
      heat. It is unclear, however, if hot environments of an equivalent thermal
      stress, as defined by a similar wet bulb globe temperature (WBGT), result in
      similar response patterns. This study examined markers of neuroendocrine (COR)
      and immune (IL-6) responses, as well as the cardiovascular and thermal responses,
      relative to changes in body heat content measured by whole-body direct
      calorimetry during work in two different hot environments with equivalent WBGT.
      Eight males performed a 2-hr heavy intermittent exercise protocol (six 15-min
      bouts of cycling at a constant rate of metabolic heat production (360W)
      interspersed by 5-min rest periods) in Hot/Dry (46 degrees C, 10% relative
      humidity [RH]) and Warm/Humid (33 degrees C, 60% RH) conditions (WBGT ~ 29
      degrees C). Whole-body evaporative and dry heat exchange, change in body heat
      content (DeltaH(b)), rectal temperature (T(re)), and heart rate were measured
      continuously. Venous blood was obtained at rest (PRE) and the end of each
      exercise bout for the measurement of changes in plasma volume (PV), plasma
      protein (an estimate of plasma water changes), COR, and IL-6. Ratings of
      perceived exertion and thermal sensation were measured during the last minute of
      each exercise bout. No differences existed for DeltaH(b), heart rate,
      T(re),%DeltaPV, plasma protein concentration, perceptual strain (thermal
      sensation, perceived exertion), and COR between the Hot/Dry and Warm/Humid
      conditions. IL-6 exhibited an interaction effect (p = 0.041), such that greater
      increases were observed in the Hot/Dry (Delta = 1.61 pg.mL(-1)) compared with the
      Warm/Humid (Delta = 0.64 pg.mL(-1)) environment. These findings indicate that
      work performed in two different hot environments with equivalent WBGT resulted in
      similar levels of thermal, cardiovascular, and perceptual strain, which support
      the use of the WBGT stress index. However, the greater IL-6 response in the
      Hot/Dry requires further research to elucidate the effects of different hot
      environments and work intensities.

PMID- 22482791
TI  - National trends in carotid artery revascularization surgery.
AB  - OBJECT: Several randomized trials have emerged with conflicting data on the
      overall safety of carotid artery stenting (CAS) in comparison with carotid
      endarterectomy (CEA). The authors hypothesize that changes in national trends
      correspond to publication of randomized trials, including an increase in
      utilization of CAS after publication of trials favorable to CAS (for example,
      Carotid and Vertebral Artery Transluminal Angioplasty Study [CAVATAS] and
      Stenting and Angioplasty with Protection in Patients at High Risk for
      Endarterectomy [SAPPHIRE]) and decrease in utilization of CAS after publication
      of trials favorable to CEA (for example, Endarterectomy versus Stenting in
      Patients with Symptomatic Severe Carotid Stenosis [EVA3-S] and Stent-Supported
      Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy [SPACE]).
      METHODS: The Nationwide Inpatient Sample was obtained for the years 1998-2008.
      Individual cases were isolated for principal diagnosis of unilateral or bilateral
      carotid artery stenosis or occlusion undergoing CEA or CAS. The percentage of CAS
      for all carotid revascularization procedures was calculated for each year.
      Perioperative inpatient morbidity, including stroke or death, were calculated and
      compared. RESULTS: The percentage of patients undergoing CAS increased yearly
      from the start of the observed period to the end, with the exception of a
      decrease in 2007. The peak utilization of CAS for carotid artery
      revascularization procedures was 15% of all cases in 2006. The stroke or death
      rate was consistent at 5% among all patients undergoing CEA for all years, while
      the incidence of stroke or death decreased among patients undergoing CAS from 9%
      in 1998 to 5% in 2008. CONCLUSIONS: The practice of CAS in the US is expanding,
      from less than 3% of all carotid artery revascularization procedures to 13% in
      2008. The utilization of CAS was seen to correlate with publication of randomized
      trials. Utilization nearly doubled in 2005 after publication of the CAS-favorable
      SAPPHIRE in 2004, and decreased by 22% after publication of the CEA-favorable EVA
      3S and SPACE in 2007. With the publication of Carotid Revascularization
      Endarterectomy Versus Stenting Trial (CREST), the authors predict a resultant
      increase in the rate of CAS for carotid artery disease in the upcoming years.

PMID- 22482792
TI  - Multimodality management of Spetzler-Martin Grade III arteriovenous
      malformations.
AB  - OBJECT: Grade III arteriovenous malformations (AVMs) are diverse because of their
      variations in size (S), location in eloquent cortex (E), and presence of central
      venous drainage (V). Because they may have implications for management and
      outcome, the authors evaluated these variations in the present study. METHODS:
      Between 1984 and 2010, 100 patients with Grade III AVMs were treated. The AVMs
      were categorized by Spetzler-Martin characteristics as follows: Type 1 = S1E1V1,
      Type 2 = S2E1V0, Type 3 = S2E0V1, and Type 4 = S3E0V0. The occurrence of a new
      neurological deficit, functional status (based on modified Rankin Scale [mRS]
      score) at discharge and follow-up, and radiological obliteration were correlated
      with demographic and morphological characteristics. RESULTS: One hundred patients
      (49 female and 51 male; age range 5-68 years, mean 35.8 years) were evaluated.
      The size of AVMs was less than 3 cm in 28 patients, 3-6 cm in 71, and greater
      than 6 cm in 1; 86 AVMs were located in eloquent cortex and 38 had central
      drainage. The AVMs were Type 1 in 28 cases, Type 2 in 60, Type 3 in 11, and Type
      4 in 1. The authors performed embolization in 77 patients (175 procedures),
      surgery in 64 patients (74 surgeries), and radiosurgery in 49 patients (44
      primary and 5 postoperative). The mortality rate following the management of
      these AVMs was 1%. Fourteen patients (14%) had new neurological deficits, with 5
      (5%) being disabling (mRS score > 2) and 9 (9%) being nondisabling (mRS score <=
      2) events. Patients with Type 1 AVMs (small size) had the best outcome, with 1
      (3.6%) in 28 having a new neurological deficit, compared with 72 patients with
      larger AVMs, of whom 13 (18.1%) had a new neurological deficit (p < 0.002). Older
      age (> 40 years), malformation size > 3 cm, and nonhemorrhagic presentation
      predicted the occurrence of new deficits (p < 0.002). Sex, eloquent cortex, and
      venous drainage did not confer any benefit. In 89 cases follow-up was adequate
      for data to be included in the obliteration analysis. The AVM was obliterated in
      78 patients (87.6%), 69 of them (88.5%) demonstrated on angiography and 9 on MRI
      /MR angiography. There was no difference between obliteration rates between
      different types of AVMs, size, eloquence, and drainage. Age, sex, and clinical
      presentation also did not predict obliteration. CONCLUSIONS: Multimodality
      management of Grade III AVMs results in a high rate of obliteration, which was
      not influenced by size, venous drainage, or eloquent location. However, the
      development of new neurological deficits did correlate with size, whereas
      eloquence and venous drainage did not affect the neurological complication rate.
      The authors propose subclassifying the Grade III AVMs according to their size (<
      3 and >= 3 cm) to account for treatment risk.

PMID- 22482793
TI  - Prevention of intraoperative cerebrospinal fluid leaks by lumbar cerebrospinal
      fluid drainage during surgery for pituitary macroadenomas.
AB  - OBJECT: Cerebrospinal fluid leakage is a major complication of transsphenoidal
      surgery. An intraoperative CSF leak, which occurs in up to 50% of pituitary tumor
      cases, is the only modifiable risk factor for postoperative leaks. Although
      several techniques have been described for surgical repair when an intraoperative
      leak is noted, none has been proposed to prevent an intraoperative CSF leak. The
      authors postulated that intraoperative CSF drainage would diminish tension on the
      arachnoid, decrease the rate of intraoperative CSF leakage during surgery for
      larger tumors, and reduce the need for surgical repair of CSF leaks. METHODS: The
      results of 114 transsphenoidal operations for pituitary macroadenoma performed
      without intraoperative CSF drainage were compared with the findings from 44 cases
      in which a lumbar subarachnoid catheter was placed before surgery to drain CSF at
      the time of dural exposure and tumor removal. RESULTS: Cerebrospinal fluid
      drainage reduced the rate of intraoperative CSF leakage from 41% to 5% (p <
      0.001). This reduction occurred in macroadenomas with (from 57% to 5%, p < 0.001)
      and those without suprasellar extension (from 29% to 0%, p = 0.31). The rate of
      postoperative CSF leakage was similar (5% vs 5%), despite the fact that
      intraoperative CSF drainage reduced the need for operative repair (from 32% to
      5%, p < 0.001). There were no significant catheter-related complications.
      CONCLUSIONS: Cerebrospinal fluid drainage during transsphenoidal surgery for
      macroadenomas reduces the rate of intraoperative CSF leaks. This preventative
      measure obviated the need for surgical repair of intraoperative CSF leaks using
      autologous fat graft placement, other operative techniques, postoperative lumbar
      drainage, and/or reoperation in most patients and is associated with minimal
      risks.

PMID- 22482794
TI  - The remarkable medical lineage of the Monro family: contributions of Alexander
      primus, secundus, and tertius.
AB  - Among the families that have influenced the development of modern medicine into
      what it is today, the Monro lineage stands as one of the most notable. Alexander
      Monro primus (1697-1767) was the first of 3 generations with the same name, a
      dynasty that spanned 126 years occupying the Chair of Anatomy one after the other
      at the University of Edinburgh. After becoming Professor of Anatomy at the
      University of Edinburgh in 1719, Monro primus played a principal role in the
      establishment of the University of Edinburgh School of Medicine and the Edinburgh
      Royal Infirmary. In 1726, he published The Anatomy of the Humane Bones, of which
      8 editions were printed during his lifetime. His son, Alexander Monro secundus
      (1733-1817), arguably the most notable of the 3 men, succeeded him as Professor
      of Anatomy. A highly regarded lecturer and anatomist, Monro secundus studied
      under many great physicians, including William Hunter and Johann Friedrich Meckel
      the Elder, and was also teacher to other well-known figures at the time, such as
      Joseph Black and Thomas Trotter. His most notable contributions include his work
      with the lymphatic system, the interventricular foramen (of Monro), and the Monro
      Kellie doctrine. Alexander Monro tertius (1773-1859), the last of the dynasty,
      also succeeded his father as Professor of Anatomy. His work included insights
      into abdominal aortic aneurysms and the anatomy of the genitourinary system. The
      prominent association of the Monro family with the University of Edinburgh and
      the effects of a tenured professorship under the concept of "Ad vitam aut culpam"
      over successive generations are also described. To the best of the authors'
      knowledge, this historical review of the Monro family is among the few published
      in neurosurgical literature. A vivid historical overview of the medical
      contributions of the most famous and influential dynasty of physicians in
      Edinburgh at that time is provided, with relevant excerpts from original
      publications.

PMID- 22482795
TI  - Cigarette smoking: a risk factor for postoperative morbidity and 1-year mortality
      following craniotomy for tumor resection.
AB  - OBJECT: Identifying risk factors for surgical morbidity and mortality might
      improve the safety and efficacy of neurosurgical intervention. Cigarette smoking
      is a relatively common practice and is associated with several adverse health
      outcomes. The authors examined the relationship between smoking and
      intraoperative blood loss, postoperative outcomes, and survival following
      craniotomy for tumor resection. METHODS: A consecutive population of patients
      undergoing craniotomy for tumor resection between 2006 and 2009 was identified.
      Using multivariable models and Cox proportional hazard regression analysis, the
      authors assessed the relation between smoking and operative outcomes including
      blood loss, complication rates, hospital length of stay, 30-day mortality, and 1
      year survival among patients who underwent craniotomy for tumor resection.
      RESULTS: A total of 453 patients were included in this study: 237 patients never
      smoked, 54 quit smoking for at least 1 year, and 162 were current smokers.
      Current smoking status was an independent risk factor for higher intraoperative
      blood loss, complication risk, and lower 1-year survival following intervention
      relative to patients who never smoked. Patients who quit smoking had
      significantly higher mean blood loss, but did not carry a higher risk for other
      outcomes such as postoperative complications and 1-year mortality compared with
      patients who never smoked. CONCLUSIONS: Current cigarette smoking is associated
      with poor surgical outcome and lower 1-year survival after undergoing craniotomy
      for tumor resection. However, quitting smoking and implementing strict smoking
      cessation programs may help mitigate these risks. Future research might
      investigate mechanisms underlying these associations.

PMID- 22482796
TI  - "Don't give me that look" - overconfidence in false mental state perception in
      schizophrenia.
AB  - Dysfunctions in social cognition are implicated in the pathogenesis of
      schizophrenia and have been extensively replicated over the years. For memory
      research, the administration of cognitive tasks with metacognitive aspects like
      confidence ratings has deepened our insight into how impairments contribute to
      symptoms of the disorder. A total of 76 patients with schizophrenia or
      schizoaffective disorder and a sample of 30 healthy participants were tested with
      the Reading the Mind in the Eyes test (Eyes-test). The Eyes-test was complemented
      with a rating scale requesting response confidence and was administered along
      with paradigms tapping neuropsychological parameters and cognitive insight.
      Schizophrenia patients showed impaired abilities on mental state perception. In
      addition, they committed more high-confidence errors and at the same time made
      fewer high-confidence correct responses. Impairments were most pronounced in
      patients with formal thought disorder. The patients displayed a decreased
      metacognitive awareness for their deficits. The results suggest that adding
      confidence ratings to the investigation of social cognition promises to advance
      our understanding of social cognition in schizophrenia. Patients not only show
      severe impairments in social cognition, but are overconfident in their judgments
      and lack cognitive insight into their deficits. The results highlight the need
      for metacognitive therapeutic approaches for the treatment of this population.

PMID- 22482797
TI  - Short communication: Concentration of TGF-beta1, IL-10 and IL-6 in boar seminal
      plasma and TGF-beta1 level in different fractions of ejaculates.
AB  - Levels of the cytokines transforming growth factor (TGF)-beta1, interleukin (IL)
      10 and IL-6 in the boar seminal plasma (SP) as well as TGF-beta1 level in
      different fractions of ejaculate were studied. These cytokines was chosen because
      of their expected effect on tissue immune response, i.e. suppressive (TGF-beta1
      and IL-10) and pro-inflammatory (IL-6). Three whole ejaculates from five boars A
      E, (n=15) were sampled weekly to evaluate the levels of seminal plasma TGF-beta1,
      IL-10 and IL-6 as well as their fluctuations over time. The effect of different
      storage temperatures, -20 degrees C or -80 degrees C, on the level of seminal
      plasma TGF beta1 was also tested (three boars, two fractions in one ejaculate).
      In addition, in 4 different fractions of ejaculates: the pre-sperm-rich (Pre
      SRF), first 10 ml of sperm-rich (10SRF), the rest of the sperm-rich fraction
      (Rest-SRF) and the rest of the ejaculate (RE) fraction, were collected from three
      boars (A-C) on four different occasions for TGF-beta1 evaluation. In the whole
      ejaculates (n=15), a wide range in the concentration of the cytokines TGF-beta1
      (20.4 - 766.5 pg/mL) and IL-10, (73.7 - 837.3 pg/mL), was found. For IL-6, the
      concentration was low (range 11.5 - 30.9 pg/ml) and only detected in four out of
      15 collections (from two boars). The mean levels of TGF-beta1 and IL-10 between
      individual boars varied but were not statistical different. The level of TGF
      beta1 in Pre-SRF, Rest-SRF and RE fractions was significantly lower in boar A
      than the other boars. A significantly higher concentration of TGF-beta1 was found
      in the 10SRF than in the other fractions. Different storage temperatures (-20
      degrees C or -80 degrees C) did not affect the seminal plasma TGF-beta1 level
      after one year of storage. To conclude: Boar seminal plasma contained TGF- beta1
      and IL-10 but with high individual variation. IL-6 was low or undetectable. The
      TGF- beta1 level was highest in the first 10 mL of the sperm-rich fraction of the
      ejaculate. Further studies are needed on the role of different levels of cytokine
      in boar semen on porcine female reproductive tissue, especially for TGF- beta1.

PMID- 22482798
TI  - Mammalian sexual dimorphism.
AB  - Sexual dimorphisms (SDs) have evolved in mammals to assure greater reproductive
      success for individuals, usually males. Secondary sexual characteristics (SSC)
      developed to further this objective, tending to be more pronounced in species
      which are polygynous, diurnal and open-habitat dwellers. Sexual selection has
      underpinned many of these changes, which are not necessarily advantageous for
      individual survival. Domestication has affected certain characteristics, more in
      terms of their quantitative rather than qualitative expression. However,
      restrictions imposed by domestication can also affect behaviors such as isolation
      and post-natal bonding while artificial selection can, by focusing on certain
      traits, cause unforeseen effects in genetically linked traits, which, when sex
      specific or sex-linked, can be reflected in SD. On a global scale, environmental
      changes can have important phylogenetic implications for species which rely upon
      environmental cues for activities as migration, hibernation and breeding,
      especially when SD occurs in response to such cues. Understanding the
      evolutionary rationale behind the development of SDs, as well as the dynamics
      which occur at the interface between natural and artificial selection, allows
      positive insights into areas as diverse as wildlife preservation and livestock
      management. For both, greatest "success" should be achieved when artificial
      selection occurs in harmony with natural selection within a supportive
      environment. Thus the aim of this review is to discuss current knowledge relating
      to the evolution, benefits and costs of mammalian sexual dimorphisms and, where
      possible, draw conclusions that might be beneficial for the husbandry and
      propagation of mammals today.

PMID- 22482799
TI  - Specific disruption of transthyretin(105-115) fibrilization using "stabilizing"
      inhibitors of transthyretin amyloidogenesis.
AB  - Transthyretin (TTR) is a cerebrospinal fluid and serum protein that undergoes
      ordered aggregation (amyloidogenesis) in familial amyloidotic polyneuropathy
      (FAP) and senile systemic amyloidosis (SSA). It is now widely accepted that
      dissociation of the native TTR tetramer is a precondition for amyloidogenesis;
      thus, molecules that stabilize the tetramer have received much attention as
      potential TTR amyloidosis inhibitors. Many of these inhibitors bind to the
      thyroxine (T(4)) binding pocket and interact specifically with a section of the
      TTR sequence, corresponding to residues 105-115, that is implicated in
      amyloidogenic propensity. In this work, we study the effects of "stabilizing"
      inhibitors on ordered aggregation of TTR(105-115) peptide. We show that molecules
      known to bind full-length TTR at the T(4) site are potent, specific inhibitors of
      ordered aggregation, while molecules that do not interact with TTR exhibit
      milder, nonspecific disruption through a "hyperbundling" effect. Our results
      suggest that, in addition to annealing the native tetramer, "stabilizing"
      inhibitors may also directly disrupt amyloidogenic aggregation of TTR monomers
      through specific interactions with the exposed TTR(105-115) sequence.

PMID- 22482800
TI  - The phenoxyl radical-water complex--a matrix isolation and computational study.
AB  - The phenoxyl radical 1 was generated in high yields by flash vacuum pyrolysis of
      allyl phenyl ether 2 with subsequent trapping of the products in argon at 3 K. In
      water-doped argon matrices, an OH...O complex between 1 and water is formed that
      could be characterized by IR spectroscopy. Several isotopomers of the complex
      were generated, and the IR spectra compared to results of density functional
      theory calculations. Other dimers between 1 and water were not found under these
      conditions. QM/MM calculations in simulated argon matrices reveal that an OH...pi
      complex is unstable even at a time scale of picoseconds. This finding has
      implications on the related interaction between the tyrosyl radical and the water
      in biological systems.

PMID- 22482801
TI  - Fragile X and X-linked intellectual disability: four decades of discovery.
AB  - X-Linked intellectual disability (XLID) accounts for 5%-10% of intellectual
      disability in males. Over 150 syndromes, the most common of which is the fragile
      X syndrome, have been described. A large number of families with nonsyndromal
      XLID, 95 of which have been regionally mapped, have been described as well.
      Mutations in 102 X-linked genes have been associated with 81 of these XLID
      syndromes and with 35 of the regionally mapped families with nonsyndromal XLID.
      Identification of these genes has enabled considerable reclassification and
      better understanding of the biological basis of XLID. At the same time, it has
      improved the clinical diagnosis of XLID and allowed for carrier detection and
      prevention strategies through gamete donation, prenatal diagnosis, and genetic
      counseling. Progress in delineating XLID has far outpaced the efforts to
      understand the genetic basis for autosomal intellectual disability. In large
      measure, this has been because of the relative ease of identifying families with
      XLID and finding the responsible mutations, as well as the determined and
      interactive efforts of a small group of researchers worldwide.

PMID- 22482802
TI  - Resolving the breakpoints of the 17q21.31 microdeletion syndrome with next
      generation sequencing.
AB  - Recurrent deletions have been associated with numerous diseases and genomic
      disorders. Few, however, have been resolved at the molecular level because their
      breakpoints often occur in highly copy-number-polymorphic duplicated sequences.
      We present an approach that uses a combination of somatic cell hybrids, array
      comparative genomic hybridization, and the specificity of next-generation
      sequencing to determine breakpoints that occur within segmental duplications.
      Applying our technique to the 17q21.31 microdeletion syndrome, we used genome
      sequencing to determine copy-number-variant breakpoints in three deletion-bearing
      individuals with molecular resolution. For two cases, we observed breakpoints
      consistent with nonallelic homologous recombination involving only H2 chromosomal
      haplotypes, as expected. Molecular resolution revealed that the breakpoints
      occurred at different locations within a 145 kbp segment of >99% identity and
      disrupt KANSL1 (previously known as KANSL1). In the remaining case, we found that
      unequal crossover occurred interchromosomally between the H1 and H2 haplotypes
      and that this event was mediated by a homologous sequence that was once again
      missing from the human reference. Interestingly, the breakpoints mapped
      preferentially to gaps in the current reference genome assembly, which we
      resolved in this study. Our method provides a strategy for the identification of
      breakpoints within complex regions of the genome harboring high-identity and copy
      number-polymorphic segmental duplication. The approach should become particularly
      useful as high-quality alternate reference sequences become available and genome
      sequencing of individuals' DNA becomes more routine.

PMID- 22482803
TI  - Large-scale population analysis challenges the current criteria for the molecular
      diagnosis of fascioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary myopathy
      causally linked to reduced numbers (<=8) of 3.3 kilobase D4Z4 tandem repeats at
      4q35. However, because individuals carrying D4Z4-reduced alleles and no FSHD and
      patients with FSHD and no short allele have been observed, additional markers
      have been proposed to support an FSHD molecular diagnosis. In particular a
      reduction in the number of D4Z4 elements combined with the 4A(159/161/168)PAS
      haplotype (which provides the possibility of expressing DUX4) is currently used
      as the genetic signature uniquely associated with FSHD. Here, we analyzed these
      DNA elements in more than 800 Italian and Brazilian samples of normal individuals
      unrelated to any FSHD patients. We find that 3% of healthy subjects carry alleles
      with a reduced number (4-8) of D4Z4 repeats on chromosome 4q and that one-third
      of these alleles, 1.3%, occur in combination with the 4A161PAS haplotype. We also
      systematically characterized the 4q35 haplotype in 253 unrelated FSHD patients.
      We find that only 127 of them (50.1%) carry alleles with 1-8 D4Z4 repeats
      associated with 4A161PAS, whereas the remaining FSHD probands carry different
      haplotypes or alleles with a greater number of D4Z4 repeats. The present study
      shows that the current genetic signature of FSHD is a common polymorphism and
      that only half of FSHD probands carry this molecular signature. Our results
      suggest that the genetic basis of FSHD, which is remarkably heterogeneous, should
      be revisited, because this has important implications for genetic counseling and
      prenatal diagnosis of at-risk families.

PMID- 22482804
TI  - Combined analysis of genome-wide association studies for Crohn disease and
      psoriasis identifies seven shared susceptibility loci.
AB  - Psoriasis (PS) and Crohn disease (CD) have been shown to be epidemiologically,
      pathologically, and therapeutically connected, but little is known about their
      shared genetic causes. We performed meta-analyses of five published genome-wide
      association studies on PS (2,529 cases and 4,955 controls) and CD (2,142 cases
      and 5,505 controls), followed up 20 loci that showed strongest evidence for
      shared disease association and, furthermore, tested cross-disease associations
      for previously reported PS and CD risk alleles in additional 6,115 PS cases,
      4,073 CD cases, and 10,100 controls. We identified seven susceptibility loci
      outside the human leukocyte antigen region (9p24 near JAK2, 10q22 at ZMIZ1, 11q13
      near PRDX5, 16p13 near SOCS1, 17q21 at STAT3, 19p13 near FUT2, and 22q11 at YDJC)
      shared between PS and CD with genome-wide significance (p < 5 * 10(-8)) and
      confirmed four already established PS and CD risk loci (IL23R, IL12B, REL, and
      TYK2). Three of the shared loci are also genome-wide significantly associated
      with PS alone (10q22 at ZMIZ1, p(rs1250544) = 3.53 * 10(-8), 11q13 near PRDX5,
      p(rs694739) = 3.71 * 10(-09), 22q11 at YDJC, p(rs181359) = 8.02 * 10(-10)). In
      addition, we identified one susceptibility locus for CD (16p13 near SOCS1,
      p(rs4780355) = 4.99 * 10(-8)). Refinement of association signals identified
      shared genome-wide significant associations for exonic SNPs at 10q22 (ZMIZ1) and
      in silico expression quantitative trait locus analyses revealed that the
      associations at ZMIZ1 and near SOCS1 have a potential functional effect on gene
      expression. Our results show the usefulness of joint analyses of clinically
      distinct immune-mediated diseases and enlarge the map of shared genetic risk
      loci.

PMID- 22482805
TI  - Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in
      humans and zebrafish.
AB  - Bone morphogenetic protein 1 (BMP1) is an astacin metalloprotease with important
      cellular functions and diverse substrates, including extracellular-matrix
      proteins and antagonists of some TGFbeta superfamily members. Combining whole
      exome sequencing and filtering for homozygous stretches of identified variants,
      we found a homozygous causative BMP1 mutation, c.34G>C, in a consanguineous
      family affected by increased bone mineral density and multiple recurrent
      fractures. The mutation is located within the BMP1 signal peptide and leads to
      impaired secretion and an alteration in posttranslational modification. We also
      characterize a zebrafish bone mutant harboring lesions in bmp1a, demonstrating
      conservation of BMP1 function in osteogenesis across species. Genetic,
      biochemical, and histological analyses of this mutant and a comparison to a
      second, similar locus reveal that Bmp1a is critically required for mature
      collagen generation, downstream of osteoblast maturation, in bone. We thus define
      the molecular and cellular bases of BMP1-dependent osteogenesis and show the
      importance of this protein for bone formation and stability.

PMID- 22482806
TI  - A "Copernican" reassessment of the human mitochondrial DNA tree from its root.
AB  - Mutational events along the human mtDNA phylogeny are traditionally identified
      relative to the revised Cambridge Reference Sequence, a contemporary European
      sequence published in 1981. This historical choice is a continuous source of
      inconsistencies, misinterpretations, and errors in medical, forensic, and
      population genetic studies. Here, after having refined the human mtDNA phylogeny
      to an unprecedented level by adding information from 8,216 modern mitogenomes, we
      propose switching the reference to a Reconstructed Sapiens Reference Sequence,
      which was identified by considering all available mitogenomes from Homo
      neanderthalensis. This "Copernican" reassessment of the human mtDNA tree from its
      deepest root should resolve previous problems and will have a substantial
      practical and educational influence on the scientific and public perception of
      human evolution by clarifying the core principles of common ancestry for extant
      descendants.

PMID- 22482807
TI  - A nonsense mutation in the human homolog of Drosophila rogdi causes Kohlschutter
      Tonz syndrome.
AB  - Kohlschutter-Tonz syndrome (KTS) is a rare autosomal-recessive disorder of
      childhood onset, and it is characterized by global developmental delay,
      spasticity, epilepsy, and amelogenesis imperfecta. In 12 KTS-affected individuals
      from a Druze village in northern Israel, homozygosity mapping localized the gene
      linked to the disease to a 586,513 bp region (with a LOD score of 6.4) in
      chromosomal region 16p13.3. Sequencing of genes (from genomic DNA of an affected
      individual) in the linked region revealed chr16: 4,848,632 G>A, which corresponds
      to ROGDI c.469C>T (p.Arg157(*)). The nonsense mutation was homozygous in all
      affected individuals, heterozygous in 10 of 100 unaffected individuals from the
      same Druze community, and absent from Druze controls from elsewhere. Wild-type
      ROGDI localizes to the nuclear envelope; ROGDI was not detectable in cells of
      affected individuals. All affected individuals suffered seizures, were unable to
      speak, and had amelogenesis imperfecta. However, age of onset and the severity of
      mental and motor handicaps and that of convulsions varied among affected
      individuals homozygous for the same nonsense allele.

PMID- 22482809
TI  - Managing the reproductive cycle in the bitch.
AB  - The canine estrous cycle is discussed with special emphasis on endocrinology.
      Breeding management and chemical and management strategies for estrus induction
      and suppression are described.

PMID- 22482808
TI  - Alzheimer disease susceptibility loci: evidence for a protein network under
      natural selection.
AB  - Recent genome-wide association studies have identified a number of susceptibility
      loci for Alzheimer disease (AD). To understand the functional consequences and
      potential interactions of the associated loci, we explored large-scale data sets
      interrogating the human genome for evidence of positive natural selection. Our
      findings provide significant evidence for signatures of recent positive selection
      acting on several haplotypes carrying AD susceptibility alleles; interestingly,
      the genes found in these selected haplotypes can be assembled, independently,
      into a molecular complex via a protein-protein interaction (PPI) network
      approach. These results suggest a possible coevolution of genes encoding
      physically-interacting proteins that underlie AD susceptibility and are
      coexpressed in different tissues. In particular, PICALM, BIN1, CD2AP, and EPHA1
      are interconnected through multiple interacting proteins and appear to have
      coordinated evidence of selection in the same human population, suggesting that
      they may be involved in the execution of a shared molecular function. This
      observation may be AD-specific, as the 12 loci associated with Parkinson disease
      do not demonstrate excess evidence of natural selection. The context for
      selection is probably unrelated to AD itself; it is likely that these genes
      interact in another context, such as in immune cells, where we observe cis
      regulatory effects at several of the selected AD loci.

PMID- 22482810
TI  - Clinical techniques of artificial insemination in dogs.
AB  - This article provides an overview of the current breeding techniques used in
      small animal reproduction today with an emphasis on artificial insemination
      techniques such as transvaginal and transcervical insemination as well as
      surgical deposition of semen in the uterus and oviduct. Breeding management and
      ovulation timing will be mentioned but are discussed in further detail in another
      article in this issue.

PMID- 22482811
TI  - Current advances in gestation and parturition in cats and dogs.
AB  - This article provides an overview of pregnancy in the bitch and queen. Emphasis
      will be placed on pregnancy diagnosis, monitoring pregnancy, and prevention of
      fetal loss and maternal morbidity.

PMID- 22482812
TI  - Clinical approaches to infertility in the bitch.
AB  - When presented with the apparently infertile bitch, the practitioner must sort
      through a myriad of facts, historical events, and diagnostic tests to uncover the
      etiology of the problem. Many bitches that present for infertility are
      reproductively normal and are able to conceive with appropriate intervention and
      breeding management. An algorithmic approach is helpful in cases of infertility,
      where simple questions lead to the next appropriate step. Most bitches can be
      categorized as either cyclic or acyclic, and then further classified based on
      historical data and diagnostic testing. Each female has a unique set of
      circumstances that can affect her reproductive potential. By utilizing all
      available information and a logical approach, the clinician can narrow the list
      of differentials and reach a diagnosis more quickly.

PMID- 22482813
TI  - The problem stud dog.
AB  - When presented with a dog for infertility examination, a complete history,
      physical examination, and semen evaluation should be completed. Abnormalities of
      the spermiogram should be documented and differential diagnoses determined.
      Potential causes of infertility include prostatic, testicular, epididymal,
      scrotal, vascular, neoplastic, traumatic, infectious, endocrine and autoimmune
      diseases. Failure to breed and ejaculatory disorders may also play a role. This
      article reviews the diagnostic work-up, differentials, and treatments for
      infertility in stud dogs.

PMID- 22482814
TI  - Guide to emergency interception during parturition in the dog and cat.
AB  - Clinicians in private practice, specialty practice, and emergency clinic settings
      are likely to be presented with bitches and queens with parturition emergencies.
      Parameters for the identification of dystocia include prolonged parturition,
      collapse of the dam, abnormal vaginal discharge, prolonged labor, prolonged
      interval between delivery of neonates, uterine inertia, malpresentation of the
      fetus, and large litter sizes. Methods for the diagnosis of dystocia are
      discussed. Resolution of parturition emergencies may be achieved through
      manipulative, medical, or surgical methods, although the great percentage of
      dystocia will require surgical intervention. Techniques for medical and surgical
      interception are discussed.

PMID- 22482815
TI  - Clinical approach to abortion, stillbirth, and neonatal death in dogs and cats.
AB  - This article reviews post-mortem examination, sample collection, and diagnostic
      procedures used to determine the cause of abortion, stillbirth, and neonatal
      death in dogs and cats.

PMID- 22482816
TI  - Disorders of sexual development in dogs and cats.
AB  - Determination of a mammal's sex begins at conception with the establishment of
      genotype and continues from there as the expression of specific genes directs the
      bipotential gonad to develop. The gonad further directs the sexual
      differentiation of the individual. Deviations from either of these pathways at
      any stage results in disorders of sexual development. Definitive diagnosis
      minimally requires a karyotype, histopathologic evaluation of the gonads, and
      gross description of the genital anatomy, with more complete diagnostic answers
      achieved through other diagnostic tests. This article covers normal and abnormal
      development of the reproductive organs with emphasis on diagnosis and treatment.

PMID- 22482817
TI  - Common lesions in the male reproductive tract of cats and dogs.
AB  - This article provides an overview of the lesions of the male genital tract of the
      dog and cat and covers those common diseases that affect the scrotal contents
      including testis and epididymis, the accessory genital glands especially the
      prostate, and the penis and prepuce. The majority of lesions of the male
      reproductive tract of cats and dogs are reported in dogs, and this is reflected
      in the number and types of diseases listed here. The author will attempt to
      balance simple with dramatic lesions and will start with the penis and prepuce,
      where lesions are seen more commonly.

PMID- 22482818
TI  - Common lesions in the female reproductive tract of dogs and cats.
AB  - Reproductive lesions are commonly seen in small animal practice. Lesions in the
      ovaries, uterus, and vagina may seriously influence normal reproductive capacity
      of dogs and cats and may put at risk the general health of the patients. The
      objective of this article is to give the veterinary practitioner a current and
      concise guide to the clinical signs, intraoperative changes, diagnosis, and
      treatment/management of lesions in the reproductive tract of the bitch and queen
      commonly seen in practice.

PMID- 22482819
TI  - Bacterial reproductive pathogens of cats and dogs.
AB  - With the notable exception of Brucella canis, exogenous bacterial pathogens are
      uncommon causes of reproductive disease in cats and dogs. Most bacterial
      reproductive infections are endogenous, and predisposing factors for infection
      are important. This article reviews the etiology, pathogenesis, clinical
      presentation, diagnosis, treatment, and public health significance of bacterial
      reproductive pathogens in cats and dogs.

PMID- 22482820
TI  - Viral reproductive pathogens of dogs and cats.
AB  - This article reviews the current literature on the viral agents that cause
      reproductive failures in domestic carnivores (dogs and cats). A meaningful update
      is provided on the etiologic, clinical, pathologic, diagnostic, and prophylactic
      aspects of the viral infections impacting canine and feline reproduction as a
      consequence of either direct virus replication or severe debilitation of pregnant
      animals.

PMID- 22482821
TI  - Small animal theriogenology.

PMID- 22482822
TI  - Assessing relative bioactivity of chemical substances using quantitative
      molecular network topology analysis.
AB  - Structurally different chemical substances may cause similar systemic effects in
      mammalian cells. It is therefore necessary to go beyond structural comparisons to
      quantify similarity in terms of their bioactivities. In this work, we introduce a
      generic methodology to achieve this on the basis of Network Biology principles
      and using publicly available molecular network topology information. An
      implementation of this method, denoted QuantMap, is outlined and applied to
      antidiabetic drugs, NSAIDs, 17beta-estradiol, and 12 substances known to disrupt
      estrogenic pathways. The similarity of any pair of compounds is derived from
      topological comparison of intracellular protein networks, directly and indirectly
      associated with the respective query chemicals, via a straightforward pairwise
      comparison of ranked proteins. Although output derived from straightforward
      chemical/structural similarity analysis provided some guidance on bioactivity,
      QuantMap produced substance interrelationships that align well with reports on
      their respective perturbation properties. We believe that QuantMap has potential
      to provide substantial assistance to drug repositioning, pharmacology evaluation,
      and toxicology risk assessment.

PMID- 22482823
TI  - Fuzzy nanoassembly of polyelectrolyte and layered clay multicomposite toward a
      reliable gas barrier.
AB  - Flexible and transparent gas-diffusion barriers have played an important role in
      recent years. The present study describes a flexible barrier film with a tailored
      architecture of cationic polyelectrolytes and clay/polymer nanoassemblies. Highly
      oriented and well-aligned barrier films were achieved by the consecutive
      absorption of flexible cationic polymer and anionic montmorillonite platelets.
      The experimental results showed that the layer-by-layer deposition of oppositely
      charged thin films containing self-assembled poly(vinyl alcohol) and
      montmorillonites improved their gas barrier characteristics based on the Ca
      degradation test, enhancing their optical transparency. This nanostructure,
      fabricated using a solution process, is useful in many applications, for example,
      flexible and moisture-free organic electronics. This simple and fast method is
      suitable for the mass coating of large surface areas, as required in industry.

PMID- 22482824
TI  - Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative
      emergency patients.
AB  - BACKGROUND: Neurosyphilis is known as "the great imitator" or "the great
      impostor" because of its wide range of clinical symptoms. A high misdiagnosis
      rate of ischemic stroke was observed among neurosyphilis patients in clinical
      practice, which prevents patients from receiving the most appropriate treatment,
      and often results in more severe neurologic damage. METHODS: A total of 149
      neurosyphilis patients were retrospectively reviewed. The control group comprised
      1570 non-neurosyphilitic ischemic stroke patients. The proportion of patients
      with ischemic stroke as the primary symptom of the different types of
      neurosyphilis and the misdiagnosis rate of neurosyphilitic ischemic stroke were
      analyzed, including the risk factors for cardiovascular disease. RESULTS: Among
      the 149 neurosyphilis patients, 21 (14.09%) developed ischemic stroke as a
      primary symptom, including three cases of syphilitic meningitis and 18 cases of
      meningovascular neurosyphilis. Only four of the neurosyphilis patients had
      histories of ischemic stroke and recurrence. The other 17 cases were treated for
      the first time in the emergency department; however, none of the patients were
      initially suspected of neurosyphilitic ischemic stroke. All of the patients were
      only diagnosed with neurosyphilis during their follow-up treatment. The
      misdiagnosis rate of neurosyphilitic ischemic stroke was as high as 80.95%
      (17/21). Furthermore, except for hypertension, no significant differences in
      cardiovascular risk factors were observed between the groups (P>0.05).
      CONCLUSIONS: In clinical practice, particularly during emergencies, any ischemic
      stroke patient should be screened for neurosyphilis.

PMID- 22482825
TI  - Female cluster headache in the United States of America: what are the gender
      differences? Results from the United States Cluster Headache Survey.
AB  - OBJECTIVE: To present results from the United States Cluster Headache Survey
      regarding gender differences in cluster headache demographics, clinical
      characteristics, diagnostic delay, triggers, treatment response and personal
      burden. BACKGROUND: Very few studies have looked at the gender differences in
      cluster headache presentation. The United States Cluster Headache Survey is the
      largest study of cluster headache sufferers ever completed in the United States
      and it is also the largest study of female cluster headache patients ever
      presented. METHODS: The total survey consisted of 187 multiple choice questions
      which dealt with various issues related to cluster headache including:
      demographics, clinical characteristics, concomitant medical conditions, family
      history, triggers, smoking history, diagnosis, treatment response and personal
      burden. A group of questions were specifically targeted to female cluster
      headache patients. The survey was placed on a website from October to December
      2008. For all survey responders the diagnosis of cluster headache needed to be
      made by a neurologist but there was no validation of the headache diagnosis by
      the authors. RESULTS: 1134 individuals completed the survey (816 male, 318
      female). Key Points that define the differences between female and male cluster
      headache include: a. Age of onset: women develop cluster headache at an earlier
      age than men and are more likely to develop a second peak of cluster headache
      onset after 50 years of age. b. Family history: woman cluster headache sufferers
      are more likely to have a family history of both cluster headache and migraine
      and have an increased familial risk of Parkinson's disease. c. Comorbid
      conditions: female cluster headaches sufferers are significantly more likely to
      experience depression and have asthma than males. d. Aura issues: aura with
      cluster headache is equally common in both sexes, but aura duration is shorter in
      women. Women are much more likely to experience sensory, language and brainstem
      auras. e. Pain location: cluster headache pain is typically retro-orbital in
      location in both sexes but women are significantly more likely to experience
      cluster headache pain in the jaw, cheek and ear than men. f. Associated symptoms:
      women with cluster headache develop more "migrainous" associated symptoms than
      men, especially nausea and they are also more likely to have self-injurious
      behavior than men. g. Triggers: women with cluster headache are much less likely
      to have alcohol trigger a headache, but are significantly more likely to have
      "migrainous" triggers for their cluster headaches than men. h. Smoking issues:
      women are much less likely to have a smoking history than male cluster headache
      sufferers, more likely to have never smoked prior to cluster headache onset. i.
      Cycle issues: spring and fall are the most common time to start a cluster
      headache cycle in both sexes. Women are statistically significantly less likely
      to start a cluster headache cycle in the months of October-December than men.
      Women have more attacks per day and higher pain intensity nighttime attacks than
      men. j. TREATMENT: in regard to acute treatment women statistically were less
      response to sumatriptan injectable and nasal spray than men, but statistically
      more likely to respond to inhaled lidocaine. There was equal efficacy in the
      sexes to inhaled oxygen but slower response in women. For preventive treatment no
      significant gender differences were noted, but overall women were less responsive
      to almost all preventives than men. k. Diagnostic delay: there remains a
      significant diagnostic delay for cluster headache patients in both sexes but
      women were more likely to be diagnosed after 10 years of symptom onset than males
      and significantly fewer women were diagnosed correctly at an initial physician
      visit than men. l. Female specific issues: cluster headache does not appear to be
      influenced by menses or menopause but 50% of the survey responders stated their
      headaches improved with pregnancy. Cluster headache does not appear to alter
      fertility rates in female cluster headache sufferers. m. Personal burden: cluster
      headache causes significantly more personal burden in women than men with more
      loss of employment and/or need of disability, as well as more homebound days.
      CONCLUSION: Overall women and men with cluster headache have a similar
      presentation but there are some distinct differences that have been suggested in
      smaller studies of female cluster headache that we have now verified, while some
      of our study conclusions have not been shown previously. One major limitation to
      the study is a lack of validation of diagnosis. A substantial false positive
      cluster headache diagnosis rate, especially in females, cannot be excluded by the
      study methods utilized.

PMID- 22482826
TI  - Subsurface femtosecond tissue alteration: selectively photobleaching macular
      degeneration pigments in near retinal contact.
AB  - This paper uses advances in the ultrafast manipulation of light to address a
      general need in medicine for a clinical approach that can provide a solution to a
      variety of disorders requiring subsurface tissue manipulation with ultralow
      collateral damage. Examples are age-related macular degeneration (AMD), fungal
      infections, tumors surrounded by overlying tissue, cataracts, etc. Although
      lasers have revolutionized the use of light in clinical settings, most lasers
      employed in medicine cannot address such problems of depth-selective tissue
      manipulation. This arises from the fact that they are mostly based on one photon
      based laser tissue interactions that provide a cone of excitation where the
      energy density is sufficiently high to excite heat or fluorescence in the entire
      cone. Thus, it is difficult to excite a specific depth of a tissue without
      affecting the overlying surface. However, the advent of femtosecond (fs) lasers
      has caused a revolution in multiphoton microscopy (Zipfel et al. Nat. Biotechnol.
      2003, 21, 1369-1377; Denk et al. Science 1990, 248, 73-76) and fabrication
      (Kawata et al. Nature 2001, 412, 697-698). With such lasers, the photon energy
      density is only high enough for multiphoton processes in the focal volume, and
      this opens a new direction to address subsurface tissue manipulation. Here we
      show in an AMD animal model, Ccr2 KO knockout mutant mice, noninvasive, selective
      fs two-photon photobleaching of pigments associated with AMD that accumulate
      under and in ultraclose proximity to the overlying retina. Pathological evidence
      is presented that indicates the lack of collateral damage to the overlying retina
      or other surrounding tissue.

PMID- 22482827
TI  - One-pot synthesis of aptamer-functionalized silver nanoclusters for cell-type
      specific imaging.
AB  - As an emerging category of fluorescent metal nanoclusters, oligonucleotide
      templated silver nanoclusters (Ag NCs) have attracted a lot of interest and have
      shown wide application in biorelated disciplines. However, the weak fluorescence
      emission and poor permeability to cell membranes tethered further intracellular
      applications of Ag NCs. AS1411 is an antiproliferative G-rich phosphodiester
      oligonucleotide and currently an anticancer agent under phase II clinical trials.
      Herein, we present a strategy to synthesize AS1411-functionalized Ag NCs with
      excellent fluorescence through a facile one-pot process. Confocal laser scanning
      microscopy and Z-axis scanning confirmed that the AS1411-functionalized Ag NCs
      could be internalized into MCF-7 human breast cancer cells and were able to
      specifically stain nuclei with red color. To our surprise, 3-[4,5-dimethylthiazol
      z-yl]-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated the Ag NCs were
      cytocompatible and showed better inhibition effects than pure AS1411 on MCF-7
      human breast cancer cells. In addition, a universal design of the oligonucleotide
      scaffold for synthesis of Ag NCs was extended to other aptamers, such as Sgc8c
      and mucin 1 aptamer. Due to the facile synthesis procedure and capability of
      specific target recognition, this fluorescent platform will potentially broaden
      the applications of Ag NCs in biosensing and biological imaging.

PMID- 22482828
TI  - Significance of EpCAM and TROP2 expression in non-small cell lung cancer.
AB  - BACKGROUND: The tumor-associated calcium signal transducer (TACSTD) genes,
      originally designated epithelial cell adhesion molecule (EpCAM) and TROP2,
      represent true oncogenes. Little is known about EpCAM and TROP2 gene expression
      in non-small cell lung carcinoma (NSCLC). This study evaluated EpCAM and TROP2
      protein expression and clinicopathologic significance in cases of NSCLC. METHODS:
      Tissue microarray blocks acquired from 164 cases of NSCLC, including 100 cases of
      adenocarcinoma (AdC) and 64 of squamous cell carcinoma (SCC), were examined by
      immunohistochemical staining for EpCAM, and TROP2. The results were correlated
      with clinicopathologic data. RESULTS: EpCAM and TROP2 were significantly
      overexpressed in SCC than in AdC (P < 0.01). In AdC, EpCAM overexpression was
      closely related to sex, histologic grade, pathologic T stage, pathologic N stage,
      and TNM stage, and TROP2 overexpression was only related to histologic grade (P <
      0.05, respectively). In SCC, correlations were evident between EpCAM
      overexpression and TNM stage (P = 0.01), and between TROP2 overexpression and
      pathologic T stage (P = 0.02). EpCAM overexpression showed no significance with
      overall survival in AdC and SCC patients. However, TROP2 overexpression in AdC
      had a positive influence on overall survival (P = 0.02) and disease-free survival
      (P = 0.03). In particular, AdC patients with stage II or III showed better
      overall survival (P = 0.05) and disease-free survival (P = 0.04). CONCLUSIONS:
      While EpCAM and TROP2 show weak and non-complete membranous staining in normal
      bronchial epithelium and pneumocyte, their complete membranous expression in
      carcinoma suggests their role in carcinogenesis. EpCAM and TROP2 were more
      frequently overexpressed in SCC. EpCAM overexpression had no prognostic value in
      this study, but TROP2 overexpression showed better survival in AdC patients and
      might be a better prognostic marker in advanced stage AdC.

PMID- 22482829
TI  - No evidence for an association between ABO blood group and overall ischemic
      stroke or any of the major etiologic subtypes.
AB  - INTRODUCTION: The ABO blood group system is encoded by one gene, ABO. Previous
      studies have reported an association between blood group non-O (i.e. phenotype A,
      B or AB) and myocardial infarction. Studies on stroke and ABO are, however, more
      scarce. Therefore, we aimed to investigate whether ABO phenotype or genotype is
      associated with ischemic stroke and/or etiologic subtypes of ischemic stroke.
      MATERIALS AND METHODS: The study was performed in the Sahlgrenska Academy Study
      on Ischemic Stroke (SAHLSIS), which comprises 600 patients with ischemic stroke
      before the age of 70 years, and 600 matched controls. Patients were classified
      according to the TOAST criteria. RESULTS: There was no significant association
      between ABO phenotype (blood group O vs. non-O) and overall ischemic stroke
      (multivariable odds ratio of 0.9, 95% confidence interval 0.7-1.2). This was also
      true for blood group O vs. A and O vs. B. Furthermore, no association between ABO
      genotypes and ischemic stroke was detected. The ischemic stroke subtype analysis
      was confined to large-vessel disease, small-vessel disease, cardioembolic stroke
      and cryptogenic stroke. In this analysis, there was no significant association
      between any ischemic stroke subtype and ABO phenotype or genotype. CONCLUSIONS:
      The findings in this study suggest that ABO phenotype or genotype does not have a
      major impact in the pathophysiology of ischemic stroke or any of the ischemic
      stroke subtypes.

PMID- 22482830
TI  - Clinical relevance of pulmonary infarction in patients with pulmonary embolism.
AB  - INTRODUCTION: Data regarding the clinical relevance of pulmonary infarction (PI)
      in patients with pulmonary embolism (PE) are lacking. The aim of this study was
      to investigate the clinical features of PE patients with PI and the prognostic
      role of PI for PE patients. MATERIALS AND METHODS: Based on computed tomography
      scan, 509 patients with PE were divided into two groups, the infarction group
      (n=45) and the non-infarction group (n=464). A variety of clinical parameters
      were compared between the two groups. RESULTS: In the infarction group, the
      largest pulmonary arteries involved by emboli were central rather than peripheral
      and more proximal as compared to the non-infarction group (p=0.01 and p<0.03,
      respectively). Thrombolytic agents tended to be more frequently administered in
      the infarction group (13.3% [n=6] versus 6.3% [n=29], p=0.07). In-hospital
      mortality, PE-related deaths, and the recurrence rate of PE did not differ
      between the two groups. CONCLUSIONS: The present study did not demonstrate that
      PI is a prognostic indicator of recurrence and mortality in PE patients. We
      suggest the possibility that blood clot burden is greater in PE patients with PI,
      although PI by itself occurs in small pulmonary arteries.

PMID- 22482831
TI  - Similarities in thromboelastometric (ROTEM(r)) findings between humans and
      baboons.
AB  - INTRODUCTION: Interest in visco-elastic testing in different clinical scenarios
      has increased but few data are available on thromboelastometric findings in
      primates. MATERIALS AND METHODS: Blood cell count (hemoglobin, hematocrit,
      platelet count), coagulation parameters (prothrombin time, International
      Normalized Ratio, fibrinogen), and ROTEM(r) (Tem International GmbH, Munich,
      Germany) variables were analyzed using blood from 25 anesthetized male baboons
      and 21 non-anesthetized healthy volunteers. The platelet component of the clot
      was calculated as the difference in maximum clot elasticity (MCE) between the
      whole blood clot (EXTEM test) and the fibrin-based clot (FIBTEM test). In
      subgroups of each species, 10 MUg abciximab was added to the regular FIBTEM
      reagent (cytochalasin D) for additional platelet inhibition. RESULTS: Blood cell
      count was comparable between humans and primates. Both fibrinogen concentration
      (p<0.0001) and maximum clot firmness (MCF) in FIBTEM assays were significantly
      lower in baboons (p>0.0001, and p=0.006, respectively). PT, INR, and clotting
      time in NATEM assays were significantly prolonged in humans compared with
      baboons. MCF in NATEM, EXTEM and INTEM assays was not different between baboons
      and humans. Clot lysis in NATEM, EXTEM and INTEM assays was significantly higher
      in humans (p<0.0001). In contrast FIBTEM clot lysis was significantly higher in
      baboons (p=0.01). Addition of abciximab into the FIBTEM assay resulted in a
      significant reduction in MCF and MCE (p<0.001) and, consequently, the platelet
      component increased similar in both humans and baboons (p<0.001). CONCLUSION:
      Activated ROTEM(r) tests revealed broad similarities between humans and baboons.
      ROTEM(r) assays developed for use in humans can also be used in baboons.

PMID- 22482833
TI  - Cholestasis is associated with hepatic microvascular dysfunction and aberrant
      energy metabolism before and during ischemia-reperfusion.
AB  - AIMS: The aim was to investigate the impact of ischemia-reperfusion (I/R) on
      intrahepatic oxidative stress, oxidative phosphorylation, and nucleotide
      metabolism in relation to liver damage and inflammation in cholestatic rats to
      elucidate the molecular mechanisms responsible for post-I/R pathogenesis during
      cholestasis. RESULTS: Pre-I/R cholestatic livers exhibited mild hepatopathology
      in the form of oxidative/nitrosative stress, perfusion defects, necrosis and
      apoptosis, inflammation, and fibrosis. Plasma bilirubin concentration in
      cholestatic livers was 190 MUM. I/R in cholestatic livers exacerbated
      hepatocellular damage and leukocyte infiltration. However, myeloperoxidase
      activity in neutrophils at 6 h reperfusion was not elevated in cholestatic livers
      compared to pre-I/R levels and to control (Ctrl) livers. At 6 h reperfusion,
      cholestatic livers exhibited severe histological damage, which was absent in Ctrl
      livers. Despite a lower antioxidative capacity after I/R, no cardiolipin
      peroxidation and equivalent reduced glutathione/oxidized glutathione ratios and
      Hsp70 levels were found in cholestatic livers versus Ctrls. Bilirubin acted as a
      potent and protective antioxidant. Postischemic resumption of oxidative
      phosphorylation in Ctrl livers proceeded rapidly and encompassed reactive
      hyperemia, which was significantly impaired in cholestatic livers owing to
      extensive vasoconstriction and perfusion defects. Normalization of intrahepatic
      energy status and nucleotide-based metabolic cofactors was delayed in cholestatic
      livers during reperfusion. Innovation and CONCLUSIONS: Cholestatic livers possess
      sufficient antioxidative capacity to ameliorate radical-mediated damage during
      I/R. I/R-induced damage in cholestatic livers is predominantly caused by
      microvascular perfusion defects rather than exuberant oxidative/nitrosative
      stress. The forestalled rate of oxidative phophorylation and recovery of
      bioenergetic and possibly metabolic parameters during the early reperfusion phase
      are responsible for extensive liver damage.

PMID- 22482832
TI  - Peptide LSARLAF induces integrin beta3 dependent outside-in signaling in
      platelets.
AB  - INTRODUCTION: Peptide LSARLAF (LSA) can bind and activate integrin alphaIIbbeta3
      in the absence of 'inside-out' signal. The active alphaIIbbeta3 mediates 'outside
      in' signaling that elicits platelet aggregation, granule secretion and TxA2
      production. Here we identify the membrane glycoproteins which mediate LSA-induced
      platelet activation other than alphaIIbbeta3, and determine the roles of Src,
      PLCgamma2, FcRgamma-chain, and SLP-76 in LSA-induced platelet activation. METHOD:
      Ligand-receptor binding assay was performed to study the effect of peptide LSA or
      its control peptide FRALASL (FRA) on integrins binding to their ligands.
      Spreading of CHO cells expressing alphaIIbbeta3 or alphaVbeta3 on immobilized
      fibrinogen was measured in the presence of LSA or FRA. Washed beta3, Src,
      FcRgamma-chain, LAT and SLP-76 deficient platelets aggregation and secretion were
      tested in response to LSA. RESULTS: Ligand-receptor binding assay indicated that
      LSA promoted the binding of multiple ligands to alphaIIbbeta3 or alphaVbeta3. LSA
      also enhanced CHO cells with alphaIIbbeta3 or alphaVbeta3 expression spreading on
      immobilized fibrinogen. beta3 deficient platelets failed to aggregate and secrete
      in response to LSA. The phosphorylation of PLCgamma2 and Syk was also beta3
      dependent. Src, FcRgamma-chain, LAT and SLP-76 deficient platelets did not
      aggregate, secrete ATP or produce TxA2 in response to LSA. CONCLUSION: LSA
      induced platelet activation is beta3 dependent, and signaling molecules Src,
      FcRgamma-chain, SLP-76 and LAT play crucial roles in LSA-induced beta3 mediated
      signaling.

PMID- 22482834
TI  - China's air pollution control calls for sustainable strategy for the use of coal.

PMID- 22482835
TI  - Dual drug-eluting stent.

PMID- 22482836
TI  - A new method for reducing the prevalence of pneumoconiosis among coal miners:
      foam technology for dust control.

PMID- 22482837
TI  - pFiD188, the linear virulence plasmid of Rhodococcus fascians D188.
AB  - Rhodococcus fascians is currently the only phytopathogen of which the virulence
      genes occur on a linear plasmid. To get insight into the origin of this replicon
      and into the virulence strategy of this broad-spectrum phytopathogen, the
      sequence of the linear plasmid of strain D188, pFiD188, was determined. Analysis
      of the 198,917 bp revealed four syntenic regions with linear plasmids of R.
      erythropolis, R. jostii, and R. opacus, suggesting a common origin of these
      replicons. Mutational analysis of pFi_086 and pFi_102, similar to cutinases and
      type IV peptidases, respectively, showed that conserved region R2 was involved in
      plasmid dispersal and pointed toward a novel function for actinobacterial
      cutinases in conjugation. Additionally, pFiD188 had three regions that were
      unique for R. fascians. Functional analysis of the stk and nrp loci of regions U2
      and U3, respectively, indicated that their role in symptom development was
      limited compared with that of the previously identified fas, att, and hyp
      virulence loci situated in region U1. Thus, pFiD188 is a typical rhodococcal
      linear plasmid with a composite structure that encodes core functions involved in
      plasmid maintenance and accessory functions, some possibly acquired through
      horizontal gene transfer, implicated in virulence and the interaction with the
      host.

PMID- 22482839
TI  - Living with the enemy or uninvited guests: functional genomics approaches to
      investigating host resistance or tolerance traits to a protozoan parasite,
      Theileria annulata, in cattle.
AB  - Many breeds of cattle with long histories of living in areas of endemic disease
      have evolved mechanisms that enable them to co-exist with specific pathogens.
      Understanding the genes that control tolerance and resistance could provide new
      strategies to improve the health and welfare of livestock. Around one sixth of
      the world cattle population is estimated to be at risk from one of the most
      debilitating tick-borne diseases of cattle, caused by the protozoan parasite,
      Theileria annulata. The parasite mainly infects cells of the myeloid lineage
      which are also the main producers of inflammatory cytokines. If an infectious or
      inflammatory insult is sufficiently great, inflammatory cytokines produced by
      macrophages enter the circulation and induce an acute phase proteins (APP)
      response. The Bos taurus Holstein breed produces higher and more prolonged levels
      of inflammatory cytokine induced APP than the Bos indicus Sahiwal breed in
      response to experimental infection with T. annulata. The Sahiwal exhibits
      significantly less pathology and survives infection, unlike the Holstein breed.
      Therefore, we hypothesised that the causal genes were likely to be expressed in
      macrophages and control the production of inflammatory cytokines. A functional
      genomics approach revealed that the transcriptome profile of the B. taurus
      macrophages was more associated with an inflammatory programme than the B.
      indicus macrophages. In particular the most differentially expressed gene was a
      member of the signal regulatory protein (SIRP) family. These are mainly expressed
      on myeloid cell surfaces and control inflammatory responses. Other differentially
      expressed genes included bovine major histocompatibility complex (MHC) (BoLA)
      class II genes, particularly BoLA DQ, and transforming growth factor (TGF)B2. We
      are now exploring whether sequence and functional differences in the bovine SIRP
      family may underlie the resistance or tolerance to T. annulata between the
      breeds. Potentially, our research may also have more general implications for the
      control of inflammatory processes against other pathogens. Genes controlling the
      balance between pathology and protection may determine how livestock can survive
      in the face of infectious onslaught. Next generation sequencing and RNAi
      methodologies for livestock species will bring new opportunities to link
      diversity at the genome level to functional differences in health traits in
      livestock species.

PMID- 22482838
TI  - Fluorescence characterization of the transfer RNA-like domain of transfer
      messenger RNA in complex with small binding protein B.
AB  - Transfer messenger RNA (tmRNA) and small binding protein B (SmpB) are the main
      components of the trans-translation rescue machinery that releases stalled
      ribosomes from defective mRNAs. Little is known about how SmpB binding affects
      the conformation of the tRNA-like domain (TLD) of tmRNA. It has been previously
      hypothesized that the absence of a D stem in the TLD provides flexibility in the
      elbow region of tmRNA, which can be stabilized by its interaction with SmpB.
      Here, we have used Forster resonance energy transfer to characterize the global
      structure of the tRNA-like domain of tmRNA in the presence and absence of SmpB
      and as a function of Mg(2+) concentration. Our results show tight and specific
      binding of SmpB to tmRNA. Surprisingly, our data show that the global
      conformation and flexibility of tmRNA do not change upon SmpB binding. However,
      Mg(2+) ions induce an 11 A compaction in the tmRNA structure, suggesting that the
      flexibility in the H2a stem may allow different conformations of tmRNA as the TLD
      and mRNA-like domain need to be positioned differently while moving through the
      ribosome.

PMID- 22482840
TI  - Changing US and world demographics: consequences for the practice of medicine.

PMID- 22482841
TI  - Thrombolytics and vena cava filters decrease mortality in patients with unstable
      pulmonary embolism.

PMID- 22482842
TI  - Caveat promisor: the potential pitfalls of clinical guarantees.

PMID- 22482843
TI  - Salt and hypertension: is salt dietary reduction worth the effort?
AB  - In numerous epidemiologic, clinical, and experimental studies, dietary sodium
      intake has been linked to blood pressure, and a reduction in dietary salt intake
      has been documented to lower blood pressure. In young subjects, salt intake has a
      programming effect in that blood pressure remains elevated even after a high salt
      intake has been reduced. Elderly subjects, African Americans, and obese patients
      are more sensitive to the blood pressure-lowering effects of a decreased salt
      intake. Depending on the baseline blood pressure and degree of salt intake
      reduction, systolic blood pressure can be lowered by 4 to 8 mm Hg. A greater
      decrease in blood pressure is achieved when a reduced salt intake is combined
      with other lifestyle interventions, such as adherence to Dietary Approaches to
      Stop Hypertension. A high salt intake has been shown to increase not only blood
      pressure but also the risk of stroke, left ventricular hypertrophy, and
      proteinuria. Adverse effects associated with salt intake reduction, unless
      excessive, seem to be minimal. However, data linking a decreased salt intake to a
      decrease in morbidity and mortality in hypertensive patients are not unanimous.
      Dietary salt intake reduction can delay or prevent the incidence of
      antihypertensive therapy, can facilitate blood pressure reduction in hypertensive
      patients receiving medical therapy, and may represent a simple cost-saving
      mediator to reduce cardiovascular morbidity and mortality.

PMID- 22482844
TI  - Nonspecific but significant.

PMID- 22482845
TI  - Case fatality rate with pulmonary embolectomy for acute pulmonary embolism.
AB  - BACKGROUND: There are insufficient data to assess the potential role of pulmonary
      embolectomy in patients with acute pulmonary embolism. METHODS: In-hospital all
      cause case fatality rate with pulmonary embolectomy was assessed from the
      Nationwide Inpatient Sample from 1999 through 2008. RESULTS: Among unstable
      patients (in shock or ventilator-dependent), case fatality rate with embolectomy
      was 380 of 950 (40%). Among stable patients, case fatality rate was lower: 690 of
      2820 (24%) (P <.0001). Case fatality rate in unstable patients was 39% in 1999
      2003 and 40% in 2004-2008 (not significant), and in stable patients it was 27% in
      1999-2003 and 23% in 2004-2008 (P=.01). Case fatality rates were lower in
      patients with a primary diagnosis of pulmonary embolism and even lower in
      patients with a primary diagnosis who had none of the comorbid conditions listed
      in the Charlson Index. Within each stratified group, patients with vena cava
      filters had a lower case fatality rate. CONCLUSIONS: Case fatality rate in
      unstable patients who underwent pulmonary embolectomy remained at 39%-40% from
      1999-2003 to 2004-2008, and in stable patients it decreased only from 27% to 23%.
      Case fatality rates were lower in those with fewer comorbid conditions and in
      those who received a vena cava filter. Our data reflect average outcome in the
      US. It may be that experienced surgeons and an aggressive multidisciplinary team
      could obtain a lower case fatality rate.

PMID- 22482846
TI  - Exercise is associated with a reduced incidence of sleep-disordered breathing.
AB  - BACKGROUND: The effect of exercise on sleep-disordered breathing is unknown.
      While diet and weight loss have been shown to reduce the severity of sleep
      disordered breathing, it is unclear whether exercise has an independent effect.
      METHODS: A population-based longitudinal epidemiologic study of adults measured
      the association between exercise and incidence and severity of sleep-disordered
      breathing. Hours of weekly exercise were assessed by 2 mailed surveys (1988 and
      2000). Sleep-disordered breathing was assessed by 18-channel in-laboratory
      polysomnography at baseline and at follow-up. RESULTS: Associations were modeled
      using linear and logistic regression, adjusting for body mass index, age, sex,
      and other covariates. Hours of exercise were associated with reduced incidence of
      mild (odds ratio 0.76, P=.011) and moderate (odds ratio 0.67, P=.002) sleep
      disordered breathing. A decrease in exercise duration also was associated with
      worsening sleep-disordered breathing, as measured by the apnea-hypopnea index
      (beta=2.368, P=.048). Adjustment for body mass index attenuated these effects.
      CONCLUSIONS: Exercise is associated with a reduced incidence of mild and moderate
      sleep-disordered breathing, and decreasing exercise is associated with worsening
      of sleep-disordered breathing. The effect of exercise on sleep-disordered
      breathing appears to be largely, but perhaps not entirely, mediated by changes in
      body habitus.

PMID- 22482847
TI  - Determinants of high-sensitivity troponin T among patients with a noncardiac
      cause of chest pain.
AB  - BACKGROUND: It is unknown to what extent noncardiac causes, including renal
      dysfunction, may contribute to high-sensitivity cardiac troponin T levels.
      METHODS: In an observational international multicenter study, we enrolled
      consecutive patients presenting with acute chest pain to the emergency
      department. Of 1181 patients enrolled, 572 were adjudicated by 2 independent
      cardiologists to have a noncardiac cause of chest pain. Multiple linear
      regression analyses were used to determine the important predictors of log
      transformed high-sensitivity cardiac troponin T. Kaplan-Meier curve was used to
      assess the prognostic significance of high-sensitivity cardiac troponin T>0.014
      MUg/L (99th percentile). RESULTS: A total of 88 patients (15%) had high
      sensitivity cardiac troponin T>0.014 MUg/L. Less than 50% of cardiac troponins
      could be explained by known cardiac or noncardiac diseases. In decreasing order
      of importance, age, estimated glomerular filtration rate, hypertension, previous
      myocardial infarction, and chronic kidney disease (adjusted r(2) 0.44) emerged as
      significant factors in linear regression analysis to predict high-sensitivity
      cardiac troponin T. High-sensitivity cardiac troponin T was best explained by a
      linear curve with age as <=0.014 MUg/L. Patients with high-sensitivity cardiac
      troponin T levels>0.014 MUg/L were at increased risk for all-cause mortality
      (hazard ratio 3.0; 95% confidence interval, 0.8-10.6; P=.02) during follow-up.
      CONCLUSION: Among the known covariates, age and not renal dysfunction is the most
      important determinant of high-sensitivity cardiac troponin T. Because known
      cardiac and noncardiac factors, including renal dysfunction, explain less than
      50% of high-sensitivity cardiac troponin T levels among patients with a
      noncardiac cause of chest pain, unknown or underestimated cardiac involvement
      during the acute presenting condition seems to be the major cause of elevated
      high-sensitivity cardiac troponin T.

PMID- 22482848
TI  - Chlorhexidine bathing to reduce central venous catheter-associated bloodstream
      infection: impact and sustainability.
AB  - BACKGROUND: Chlorhexidine bathing has been associated with reductions in
      healthcare-associated bloodstream infection. To determine the impact and
      sustainability of the effect of chlorhexidine bathing on central venous catheter
      associated bloodstream infection, we performed a prospective, 3-phase, multiple
      hospital study. METHODS: In the medical intensive care unit and the respiratory
      care unit of a tertiary care hospital and the medical-surgical intensive care
      units of 4 community hospitals, rates of central venous catheter-associated
      bloodstream infection were collected prospectively for each period. Pre
      intervention (phase 1) patients were bathed with soap and water or nonmedicated
      bathing cloths; active intervention (phase 2) patients were bathed with 2%
      chlorhexidine gluconate cloths with the number of baths administered and skin
      tolerability assessed; post-intervention (phase 3) chlorhexidine bathing was
      continued but without oversight by research personnel. Central venous catheter
      associated bloodstream infection rates were compared over study periods using
      Poisson regression. RESULTS: Compared with pre-intervention, during active
      intervention there were significantly fewer central venous catheter-associated
      bloodstream infections (6.4/1000 central venous catheter days vs 2.6/1000 central
      venous catheter days, relative risk, 0.42; 95% confidence interval, 0.25-0.68;
      P<.001), and this reduction was sustained during post-intervention (2.9/1000
      central venous catheter days; relative risk, 0.46; 95% confidence interval, 0.30
      0.70; P<.001). During the active intervention period, compliance with
      chlorhexidine bathing was 82%. Few adverse events were observed. CONCLUSION: In
      this multiple-hospital study, chlorhexidine bathing was associated with
      significant reductions in central venous catheter-associated bloodstream
      infection, and these reductions were sustained post-intervention when
      chlorhexidine bathing was unmonitored. Chlorhexidine bathing was well tolerated
      and is a useful adjunct to reduce central venous catheter-associated bloodstream
      infection.

PMID- 22482849
TI  - Unstable shoes increase energy expenditure of obese patients.
AB  - BACKGROUND: Ergonomic unstable shoes, which are widely available to the general
      population, could increase daily non-exercise activity thermogenesis as the
      result of increased muscular involvement. We compared the energy expenditure of
      obese patients during standing and walking with conventional flat-bottomed shoes
      versus unstable shoes. METHODS: Twenty-nine obese patients were asked to stand
      quietly and to walk at their preferred walking speed while wearing unstable or
      conventional shoes. The main outcome measures were metabolic rate of standing and
      gross and net energy cost of walking, as assessed with indirect calorimetry.
      RESULTS: Metabolic rate of standing was higher while wearing unstable shoes
      compared with conventional shoes (1.11 +/- 0.20 W/kg(-1) vs 1.06 +/- 0.23 W/kg(
      1), P=.0098). Gross and net energy cost of walking were higher while wearing
      unstable shoes compared with conventional shoes (gross: 4.20 +/- 0.42 J/kg(-1)/m(
      1)vs 4.01 +/- 0.39 J/kg(-1)/m(-1), P=.0035; net: 3.37 +/- 0.41 J/kg(-1)/m(-1) vs
      3.21 +/- 0.37 J/kg(-1)/m(-1); P=.032). CONCLUSION: In obese patients, it is
      possible to increase energy expenditure of standing and walking by means of
      ergonomic unstable footwear. Long-term use of unstable shoes may eventually
      prevent a positive energy balance.

PMID- 22482850
TI  - Accountability and transparency in graduate medical education expenditures.

PMID- 22482851
TI  - Why the (un)affordable care act should be repealed and replaced.

PMID- 22482852
TI  - Usefulness of electrocardiography for cardiovascular screening in collegiate
      athletes.

PMID- 22482854
TI  - Interleukin-10 and acute coronary syndromes.

PMID- 22482856
TI  - Anti-inflammatory cytokines: a wolf in sheep's clothing?

PMID- 22482858
TI  - A true positive nasal nodule.

PMID- 22482859
TI  - Managing chronic pain with nonopioid analgesics: a multidisciplinary consult.
AB  - As detailed in this online CME activity (www.cmeaccess.com/AJM/ChronicPain04),
      determining pain mechanism is an important aspect guiding treatment selection for
      chronic musculoskeletal pain states. Although broad classifications provide a
      framework, any combination of mechanisms may be present in a chronic pain
      patient, and there is growing evidence that pain states generally considered
      nociceptive may also involve elements of augmented central nervous system pain
      processing. Nonopioid analgesics, including serotonin norepinephrine reuptake
      inhibitors (SNRIs), tricyclic antidepressants, and alpha-2-delta ligand
      anticonvulsants, are the treatments of choice for fibromyalgia and other central
      neuropathic pain states. Additionally, studies have now shown that certain SNRIs
      can be effective in treating "classic" nociceptive pain states, such as
      osteoarthritis, and also are effective for low back pain. In addition to
      considering biological mechanisms, chronic pain management also involves
      recognizing and evaluating the contribution of psychological and sociocultural
      factors that can influence pain chronicity and patient prognosis. A
      multimodal/multidisciplinary approach incorporating pharmacologic and
      nonpharmacologic therapy into a program that includes more than 1 discipline is
      important to improve outcomes in patients with chronic pain.

PMID- 22482860
TI  - Usefulness of prominently projected aortic arch on chest radiograph to predict
      severe tortuosity of the right subclavian or brachiocephalic artery in patients
      aged >44 years undergoing coronary angiography with a right radial artery
      approach.
AB  - Although it is well known that certain characteristics, such as older age, female
      gender, hypertension, and high body mass index, are closely associated with
      severe arterial tortuosity among patients undergoing transradial coronary
      angiography, few data are available regarding useful predictors of severe
      arterial tortuosity among geriatric patients. The purpose of the present study
      was to evaluate the characteristics of geriatric patients with severe tortuosity
      of the right subclavian artery or brachiocephalic artery. The coronary
      angiographic reports of patients with severe tortuosity of the right subclavian
      artery or brachiocephalic artery and age- and gender-matched control patients
      were retrospectively evaluated. A total of 847 consecutive patients underwent
      right transradial coronary angiography. Of these patients, 48 (5.7%) had severe
      tortuosity (29 women, age 73.4 +/- 8.6 years). The factors associated with severe
      arterial tortuosity were greater body mass index (odds ratio 1.17, p = 0.02), the
      presence of a prominently projected aortic arch on a chest radiograph (odds ratio
      5.62, p <0.01), and lower serum creatinine value (odds ratio 0.05, p <0.01). In
      conclusion, the presence of a prominently projected aortic arch on the chest
      radiograph is a useful predictor of severe arterial tortuosity.

PMID- 22482861
TI  - Practices and complications of vascular closure devices and manual compression in
      patients undergoing elective transfemoral coronary procedures.
AB  - Femoral arterial puncture is the most common access method for coronary
      angiography and percutaneous coronary interventions (PCIs). Access complications,
      although infrequent, affect morbidity, mortality, costs, and length of hospital
      stay. Vascular closure devices (VCDs) are used for rapid hemostasis and early
      ambulation, but there is no consensus on whether VCDs are superior to manual
      compression (MC). A retrospective review and nested case-control study of
      consecutive patients undergoing elective transfemoral coronary angiography and
      PCI over 3 years was performed. Hemostasis strategy was performed according to
      the operators' discretion. Vascular complications were defined as groin bleeding
      (hematoma, hemoglobin decrease >=3 g/dl, transfusion, retroperitoneal bleeding,
      or arterial perforation), pseudoaneurysm, arteriovenous fistula formation,
      obstruction, or infection. Patients with postprocedure femoral vascular access
      complications were compared to randomly selected patients without complication.
      Data were available for 9,108 procedures, of which PCI was performed in 3,172
      (34.8%). MC was performed in 2,581 (28.3%) and VCDs (4 different types) were
      deployed in 6,527 procedures (71.7%). Significant complications occurred in 74
      procedures (0.81%), with 32 (1.24%) complications with MC and 42 (0.64%) with VCD
      (p = 0.004). VCD deployment failed in 80 procedures (1.23%), of which 8 (10%) had
      vascular complications. VCD use was a predictor of fewer complications (odds
      ratio 0.52, 95% confidence interval 0.33 to 0.83). In the case-control analysis,
      older age and use of large (7Fr to 8Fr) femoral sheaths were independent
      predictors of complications. In conclusion, the retrospective analysis of
      contemporary hemostasis strategies and outcomes in elective coronary procedures
      identified a low rate of complications (0.81%), with superior results after VCD
      deployment. Careful selection of hemostasis strategy and closure device may
      further decrease complication rates.

PMID- 22482862
TI  - Usefulness of circulating biomarkers for the prediction of left ventricular
      remodeling after myocardial infarction.
AB  - Left ventricular (LV) remodeling after myocardial infarction (MI) indicates a
      high risk of heart failure and death, but LV remodeling remains difficult to
      predict. Biomarkers may help to refine risk stratification for a more
      personalized medical approach. They may also shed light on the pathophysiologic
      processes involved. We performed a systematic review of the published evidence
      about the association of circulating biomarkers with LV remodeling after MI. We
      selected 59 publications. Overall, these studies examined 112 relations between
      52 different biomarkers and LV remodeling. The biomarkers most consistently
      associated with LV remodeling were involved in extracellular matrix turnover or
      neurohormonal activation: matrix metalloproteinase-9, collagen peptides, and B
      type natriuretic peptide. This review underscores the vitality of the research on
      LV remodeling but concludes that the ideal biomarker has not yet been identified.
      To reach this goal, future studies will have to be larger, have standardized
      imaging end points, and include replication populations to define optimal cutoffs
      for LV remodeling prediction. Cardiovascular magnetic resonance appears to be the
      best technique for LV remodeling assessment but its current availability may be a
      concern for recruitment for multicenter studies. Recent technologic advances will
      probably yield new candidate biomarkers of LV remodeling. Tests are necessary to
      determine whether a multimarker approach would significantly improve risk
      prediction.

PMID- 22482863
TI  - Usefulness of lung impedance-guided pre-emptive therapy to prevent pulmonary
      edema during ST-elevation myocardial infarction and to improve long-term
      outcomes.
AB  - Patients sustaining an ST-segment elevation myocardial infarction (STEMI)
      frequently develop pulmonary congestion or pulmonary edema (PED). We previously
      showed that lung impedance (LI) threshold decrease of 12% to 14% from baseline
      during admission for STEMI marks the onset of the transition zone from
      interstitial to alveolar edema and predicts evolution to PED with 98%
      probability. The aim of this study was to prove that pre-emptive LI-guided
      treatment may prevent PED and improve clinical outcomes. Five hundred sixty
      patients with STEMI and no signs of heart failure underwent LI monitoring for 84
      +/- 36 hours. Maximal LI decrease throughout monitoring did not exceed 12% in 347
      patients who did not develop PED (group 1). In 213 patients LI reached the
      threshold level and, although still asymptomatic (Killip class I), these patients
      were then randomized to conventional (group 2, n = 142) or LI-guided (group 3, n
      = 71) pre-emptive therapy. In group 3, treatment was initiated at randomization
      (LI = -13.8 +/- 0.6%). In contrast, conventionally treated patients (group 2)
      were treated only at onset of dyspnea occurring 4.1 +/- 3.1 hours after
      randomization (LI = -25.8 +/- 4.3%, p <0.001). All patients in group 2 but only 8
      patients in group 3 (11%) developed Killip class II to IV PED (p <0.001).
      Unadjusted hospital mortality, length of stay, 1-year readmission rate, 6-year
      mortality, and new-onset heart failure occurred less in group 3 (p <0.001).
      Multivariate analysis adjusted for age, left ventricular ejection fraction, risk
      factors, peak creatine kinase, and admission creatinine and hemoglobin levels
      showed improved clinical outcome in group 3 (p <0.001). In conclusion, LI-guided
      pre-emptive therapy in patients with STEMI decreases the incidence of in-hospital
      PED and results in better short- and long-term outcomes.

PMID- 22482864
TI  - Current status of preventive cardiology training among United States cardiology
      fellowships and comparison to training guidelines.
AB  - We evaluated preventive cardiology education in United States cardiology
      fellowship programs and their adherence to Core Cardiovascular Training Symposium
      training guidelines, which recommend 1 month of training, faculty with expertise,
      and clinical experience in cardiac rehabilitation, lipid disorder management, and
      diabetes management as a part of the prevention curricula. We sent an anonymous
      survey to United States cardiology program directors and their chief fellow. The
      survey assessed the program curricula, rotation structure, faculty expertise,
      obstacles, and recommended improvements. The results revealed that 24% of
      surveyed programs met the Core Cardiovascular Training Symposium guidelines with
      a dedicated 1-month rotation in preventive cardiology, 24% had no formalized
      training in preventive cardiology, and 30% had no faculty with expertise in
      preventive cardiology, which correlated with fewer rotations in prevention than
      those with specialized faculty (p = 0.009). Fellows rotated though the following
      experiences (% of programs): cardiac rehabilitation, 71%; lipid management, 37%;
      hypertension, 15%; diabetes, 7%; weight management/obesity, 6%; cardiac
      nutrition, 6%; and smoking cessation, 5%. The program directors cited "lack of
      time" as the greatest obstacle to providing preventive cardiology training and
      the chief fellows reported "lack of a developed curriculum" (p = 0.01). The most
      recommended improvement was for the American College of Cardiology to develop a
      web-based curriculum/module. In conclusion, most surveyed United States
      cardiology training programs currently do not adhere to basic preventive
      cardiovascular medicine Core Cardiovascular Training Symposium recommendations.
      Additional attention to developing curricular content and structure, including
      the creation of an American College of Cardiology on-line knowledge module might
      improve fellowship training in preventive cardiology.

PMID- 22482865
TI  - Reversible photocontrol of peptide conformation with a rhodopsin-like
      photoswitch.
AB  - Reversible photocontrol of biomolecules requires chromophores that can
      efficiently undergo large conformational changes upon exposure to wavelengths of
      light that are compatible with living systems. We designed a benzylidene
      pyrroline chromophore that mimics the Schiff base of rhodopsin and can be used to
      introduce light-switchable intramolecular cross-links in peptides and proteins.
      This new class of photoswitch undergoes an ~10 A change in end-to-end distance
      upon isomerization and can be used to control the conformation of a target
      peptide efficiently and reversibly using, alternately, violet (400 nm) and blue
      (446 nm) light.

PMID- 22482866
TI  - Chemical details on nucleolipid supramolecular architecture: molecular modeling
      and physicochemical studies.
AB  - Nucleolipids are currently under investigation as vectors for oligonucleotides
      (ON) delivery thanks to their supramolecular organization properties and their
      ability to develop specific interactions (i.e., stacking and potential Watson and
      Crick hydrogen bonds) for lipoplexes formation. To investigate the factors that
      govern the interaction events at a molecular level and optimize nucleolipid
      chemical structures, physicochemical experiments (tensiometry, AFM, BAM, and
      ellipsometry) combined with molecular dynamics simulation were performed on a
      series of zwitterionic nucleolipids (PUPC, DPUPC, PAPC) featuring a
      phosphocholine chain (PC). After construction and initial equilibration,
      simulations of pure nucleolipid bilayers were run for 100 ns at constant
      temperature and pressure, and their properties were compared to experimental data
      and to natural dipalmitoylphosphatidylcholine (DPPC) bilayers. Nucleolipid-based
      membranes are significantly more ordered and compact than DPPC bilayers mainly
      due to the presence of many intermolecular interactions between nucleoside polar
      heads. The hydrophilic phosphocholine moieties connected to the 5' hydroxyls are
      located above the bilayers, penalizing nucleic bases accessibility for further
      interactions with ON. Hence, a neutral nucleolipid (PUOH) without hydrophilic
      phosphocholine was inserted in the membranes. Simulations and experimental
      analysis of nucleolipid membranes in interaction with a single strand RNA
      structure indicate that PUOH interacts with ON in the subphase. This study
      demonstrates that molecular modeling can be used to determine the interactions
      between oligonucleotide and nucleolipids.

PMID- 22482867
TI  - The use of benthic macroinvertebrates to establish a benchmark for evaluating the
      environmental quality of microtidal, temperate southern hemisphere estuaries.
AB  - Establishment of a benchmark against which deleterious changes to an estuary can
      be evaluated requires validating that it has not been subjected to detrimental
      anthropogenic perturbations and then identifying the biological features which
      are indicative of a pristine condition and can thus be employed as indicators for
      detecting and monitoring departures from the natural state. The characteristics
      of the benthic macroinvertebrate fauna of an essentially pristine, seasonally
      open estuary in Western Australia (Broke Inlet) have been determined and compared
      with those previously recorded for a nearby eutrophic, seasonally-open estuary
      (Wilson Inlet). Density was far lower in Broke than Wilson. Compositions differed
      radically at all taxonomic levels, with polychaetes contributing less, and
      crustaceans more, to the abundance in Broke. Average taxonomic distinctness was
      greater for Broke than both Wilson and 16 other temperate southern hemisphere
      estuaries, whereas the reverse was true for variation in taxonomic distinctness,
      emphasizing that Broke Inlet is pristine.

PMID- 22482868
TI  - Ostreopsis cf. ovata (Dinophyta) bloom in an equatorial island of the Atlantic
      Ocean.
AB  - The epi-benthic dinoflagellate Ostreopsis cf. ovata Fukuyo has an increasingly
      global distribution. In Brazil there are reports of O. cf. ovata along the coast
      from 8 degrees S to 27 degrees S latitude and blooms have been registered on the
      Rio de Janeiro coastline. In the current study, an O. cf. ovata bloom is reported
      at Saint Paul's Rocks (0 degrees 55'10"N; 29 degrees 20'33"W), between the
      southern and northern hemispheres. The Archipelago is not inhabited and not
      subjected to eutrophication, due to isolation, and sustains a number of endemic
      species. Therefore, blooms of O. cf. ovata may potentially cause demise to
      trophic chains by affecting marine invertebrates and vertebrates.

PMID- 22482869
TI  - The process of continuous journal improvement: new author guidelines for
      statistical and analytical reporting in VACCINE.

PMID- 22482870
TI  - Short latency afferent inhibition associated with cortical compression and memory
      impairment in patients with chronic subdural hematoma.
AB  - OBJECTIVE: To evaluate the cortical excitability in patients with mild cortical
      compression. METHODS: The present study used short interval intracortical
      inhibition (SICI), intracortical facilitation (ICF), and short latency afferent
      inhibition (SAI) to evaluate motor cortex excitability in 16 chronic subdural
      hematoma (CSDH) patients with memory impairment and compared the data with those
      of 16 healthy controls. RESULTS: SAI was reduced in patients compared with
      controls (99+/-14 vs. 47+/-11% of the test size; p<0.0001, unpaired t-test). CSDH
      patients tended to have a high resting motor threshold and less pronounced SICI
      and ICF than controls, but these differences were not significant. Treatment of
      hematoma improved memory impairment and SAI in CSDH patients with wide individual
      variations that ranged from an increase of 74% to 17% of test size. CONCLUSION:
      These findings suggest that measuring SAI may provide a means of probing the
      integrity of cortical cholinergic networks in a compressed human brain.

PMID- 22482871
TI  - Ultrasound study shows nerve atrophy in post herpetic neuralgia.

PMID- 22482872
TI  - Lithium/sulfur cell discharge mechanism: an original approach for intermediate
      species identification.
AB  - The lithium/sulfur battery is a promising electrochemical system that has a high
      theoretical capacity of 1675 mAh g(-1), but its discharge mechanism is well-known
      to be a complex multistep process. As the active material dissolves during
      cycling, this discharge mechanism was investigated through the electrolyte
      characterization. Using high-performance liquid chromatography, UV-visible
      absorption, and electron spin resonance spectroscopies, we investigated the
      electrolyte composition at different discharge potentials in a TEGDME-based
      electrolyte. In this study, we propose a possible mechanism for sulfur reduction
      consisting of three steps. Long polysulfide chains are produced during the first
      reduction step (2.4-2.2 V vs Li(+)/Li), such as S(8)(2-) and S(6)(2-), as
      evidenced by UV and HPLC data. The S(3)(*-) radical can also be found in solution
      because of a disproportionation reaction. S(4)(2-) is produced during the second
      reduction step (2.15-2.1 V vs Li(+)/Li), thus pointing out the gradual decrease
      of the polysulfide chain lengths. Finally, short polysulfide species, such as
      S(3)(2-), S(2)(2-), and S(2-), are produced at the end of the reduction process,
      i.e., between 2.1 and 1.9 V vs Li(+)/Li. The precipitation of the poorly soluble
      and insulating short polysulfide compounds was evidenced, thus leading to the
      positive electrode passivation and explaining the early end of discharge.

PMID- 22482873
TI  - Assessment of the binding of hydroxylated polybrominated diphenyl ethers to
      thyroid hormone transport proteins using a site-specific fluorescence probe.
AB  - Polybrominated diphenyl ethers (PBDEs) have been shown to disrupt thyroid hormone
      (TH) functions on experimental animals, and one of the proposed disruption
      mechanisms is the competitive binding of PBDE metabolites to TH transport
      proteins. In this report, a nonradioactive, site-specific fluorescein-thyroxine
      (F-T4) conjugate was designed and synthesized as a fluorescence probe to study
      the binding interaction of hydroxylated PBDEs to thyroxine-binding globulin (TBG)
      and transthyretin (TTR), two major TH transport proteins in human plasma.
      Compared with free F-T4, the fluorescence intensity of TTR-bound conjugate was
      enhanced by as much as 2-fold, and the fluorescence polarization value of TBG
      bound conjugate increased by more than 20-fold. These changes provide signal
      modulation mechanisms for F-T4 as a fluorescence probe. Based on fluorescence
      quantum yield and lifetime measurements, the fluorescence intensity enhancement
      was likely due to the elimination of intramolecular fluorescence quenching of
      fluorescein by T4 after F-T4 was bound to TTR. In circular dichroism and
      intrinsic tryptophan fluorescence measurements, F-T4 induced similar
      spectroscopic changes of the proteins as T4 did, suggesting that F-T4 bound to
      the proteins at the T4 binding site. By using F-T4 as the fluorescence probe in
      competitive binding assays, 11 OH-PBDEs with different levels of bromination and
      different hydroxylation positions were assessed for their binding affinity with
      TBG and TTR, respectively. The results indicate that the binding affinity
      generally increased with bromine number and OH position also played an important
      role. 3-OH-BDE-47 and 3'-OH-BDE-154 bound to TTR and TBG even stronger,
      respectively, than T4. With rising environmental level and high bioaccumulation
      capability, PBDEs have the potential to disrupt thyroid homeostasis by
      competitive binding with TH transport proteins.

PMID- 22482874
TI  - The potential role of a self-management intervention for benign prostate
      hyperplasia.
AB  - OBJECTIVE: To tentatively evaluate the usefulness of self-management
      interventions in improving the lower urinary tract symptoms (LUTS) and quality of
      life (QoL) in patients with benign prostatic hyperplasia (BPH). METHODS: Two
      hundred twent-two men were recruited from a teaching hospital at Peking
      University from March 2008 to September 2009. They were referred by general
      practitioners to urologic outpatient departments because of BPH after 3-month
      administration of alpha-blockers. Participants were randomized to attend either a
      self-management program or undergo standard care. Difference of scores of
      International Prostate Symptom Score (IPSS) and BPH-specific QoL scale between 2
      groups was analyzed at the enrollment period, and at the first week, third month,
      and sixth month. RESULTS: All participants had been followed for 6 months. There
      was no significant difference in IPSS score and QoL score between the 2 groups at
      the enrollment period and first week, whereas at the third month and sixth month,
      the IPSS scores and QoL self-management interventional group scores were
      statistically significant lower than those of the standard care group.
      CONCLUSION: Self-management intervention may be associated with decreased LUTS
      symptoms and may improve QoL in BPH patients with alpha-blocker administration.

PMID- 22482876
TI  - Editorial comment.

PMID- 22482877
TI  - Utilizing peptidic ordering in the design of hierarchical polyurethane/ureas.
AB  - One of the key design components of nature is the utilization of hierarchical
      arrangements to fabricate materials with outstanding mechanical properties.
      Employing the concept of hierarchy, a new class of segmented polyurethane/ureas
      (PUUs) was synthesized containing either a peptidic, triblock soft segment, or an
      amorphous, nonpeptidic homoblock block soft segment with either an amorphous or a
      crystalline hard segment to investigate the effects of bioinspired, multiple
      levels of organization on thermal and mechanical properties. The peptidic soft
      segment was composed of poly(benzyl-l-glutamate)-block-poly(dimethylsiloxane)
      block-poly(benzyl-l-glutamate) (PBLG-b-PDMS-b-PBLG), restricted to the beta-sheet
      conformation by limiting the peptide segment length to <10 residues, whereas the
      amorphous soft segment was poly(dimethylsiloxane) (PDMS). The hard segment
      consisted of either 1,6-hexamethylene diisocyanate (crystalline) or isophorone
      diisocyanate (amorphous) and chain extended with 1,4-butanediol. Thermal and
      morphological characterization indicated microphase separation in these
      hierarchically assembled PUUs; furthermore, inclusion of the peptidic segment
      significantly increased the average long spacing between domains, whereas the
      peptide domain retained its beta-sheet conformation regardless of the hard
      segment chemistry. Mechanical analysis revealed an enhanced dynamic modulus for
      the peptidic polymers over a broader temperature range as compared with the
      nonpeptidic PUUs as well as an over three-fold increase in tensile modulus.
      However, the elongation-at-break was dramatically reduced, which was attributed
      to a shift from a flexible, continuous domain morphology to a rigid, continuous
      matrix in which the peptide, in conjunction with the hard segment, acts as a
      stiff reinforcing element.

PMID- 22482878
TI  - Selective-area fluorination of graphene with fluoropolymer and laser irradiation.
AB  - We have devised a method to selectively fluorinate graphene by irradiating
      fluoropolymer-covered graphene with a laser. This fluoropolymer produces active
      fluorine radicals under laser irradiation that react with graphene but only in
      the laser-irradiated region. The kinetics of C-F bond formation is dependent on
      both the laser power and fluoropolymer thickness, proving that fluorination
      occurs by the decomposition of the fluoropolymer. Fluorination leads to a
      dramatic increase in the resistance of the graphene while the basic skeletal
      structure of the carbon bonding network is maintained. Considering the simplicity
      of the fluorination process and that it allows patterning with a nontoxic
      fluoropolymer as a solid source, this method could find application to generate
      fluorinated graphene in graphene-based electronic devices such as for the
      electrical isolation of graphene.

PMID- 22482879
TI  - Time-dependent CO2 sorption hysteresis in a one-dimensional microporous
      octahedral molecular sieve.
AB  - The development of sorbents for next-generation CO(2) mitigation technologies
      will require better understanding of CO(2)/sorbent interactions. Among the
      sorbents under consideration are shape-selective microporous molecular sieves
      with hierarchical pore morphologies of reduced dimensionality. We have
      characterized the non-equilibrium CO(2) sorption of OMS-2, a well-known one
      dimensional microporous octahedral molecular sieve with manganese oxide
      framework. Remarkably, we find that the degree of CO(2) sorption hysteresis
      increases when the gas/sorbent system is allowed to equilibrate for longer times
      at each pressure step. Density functional theory calculations indicate a "gate
      keeping" role of the cation in the tunnel, only allowing CO(2) molecules to enter
      fully into the tunnel via a highly unstable transient state when CO(2) loadings
      exceed 0.75 mmol/g. The energy barrier associated with the gate-keeping effect
      suggests an adsorption mechanism in which kinetic trapping of CO(2) is
      responsible for the observed hysteretic behavior.

PMID- 22482880
TI  - Adsorption of Cd(II) and Pb(II) onto a one step-synthesized polyampholyte:
      kinetics and equilibrium studies.
AB  - A one step-synthesized polyampholyte, bearing carboxylate and 2-methylimidazole
      (2MI) groups, was tested as adsorbent for the removal of Pb(II) and Cd(II) from
      aqueous solutions. This material combines the benefits of synthetic polymers,
      such as high adsorption capacity and chemical stability, and the advantages of
      biosorbents in regard of costs and simplicity of the production. The short time
      needed to achieve the adsorption equilibrium indicated a chemical-reaction
      controlled process. A network expansion was predicted as a result of repulsive
      interaction between the fixed positive charges. Langmuir model presented the best
      fitting to isotherm equilibrium data, with a maximum adsorption capacity of 182
      mg g(-1) for Cd(II) and 202 mg g(-1) for Pb(II). The metal removal was strongly
      dependent on pH, involving carboxylate and 2MI residues. An ion-exchange process
      for Pb(II) and Cd(II), combined with coordination for the later, were the most
      probable mechanism of interaction. The adsorption of 1.35 ppm Cd(II) was 72+/-6%
      in well-water, and the adsorption of 0.50 ppm Pb(II) was 62+/-5% in tap-water.
      The recovery figures for Cd(II) in 1% HNO(3) were optimal.

PMID- 22482881
TI  - Synthesis, characterization and adsorption properties of diethylenetriamine
      modified hypercrosslinked resins for efficient removal of salicylic acid from
      aqueous solution.
AB  - We report an effective approach for tailoring the pore textural properties and
      surface polarity of a hypercrosslinked resin to enhance its adsorption capacity
      and selectivity for removing salicylic acid from aqueous solution. Four
      hypercrosslinked resins were synthesized by controlling the reaction time of the
      self Friedel-Crafts reaction of chloromethylated polystyrene-co-divinylbenzene,
      and then modified with diethylenetriamine to adjust their surface polarity. The
      resins were characterized with N(2) adsorption for pore textural properties,
      Fourier transform infrared spectroscopy (FT-IR) for surface functional groups,
      chemical analysis for residual chlorine content and weak basic exchange capacity.
      Adsorption equilibrium, kinetics and breakthrough performance were determined for
      the removal of salicylic acid from aqueous solution on a selected resin HJ-M01.
      The equilibrium adsorption capacity of salicylic acid on HJ-M01 is significantly
      higher than that on its precursor HJ-11 and a few commercial adsorbents including
      AB-8, XAD-4 and XAD-7. The dynamic adsorption capacity of salicylic acid on HJ
      M01 was found to be 456.4 mg/L at a feed concentration of 1000 mg/L and 294 K.
      The used resin could be fully regenerated with 1% sodium hydroxide solution. The
      hypercrosslinked resins being developed were promising alternatives to commercial
      adsorbents for removing salicylic acid and other volatile organic compounds
      (VOCs) from aqueous solution.

PMID- 22482882
TI  - Concomitant activation of miR-107/PDCD10 and hypoxamir-210/Casp8ap2 and their
      role in cytoprotection during ischemic preconditioning of stem cells.
AB  - AIMS: To establish a functional link between microRNA-107 (miR-107) and stem cell
      survival during ischemic preconditioning (IPC) of stem cells with multiple cycles
      of brief anoxia/re-oxygenation (10 or 30 min, one to three cycles) and show that
      the cytoprotective effects were independent of hypoxamir-210. RESULTS: We
      demonstrated the induction of miR-107 in response to the IPC-induced activation
      of Akt/hypoxia inducible factor-1alpha (HIF-1alpha) in preconditioned mesenchymal
      stem cells ((PC)MSC), which showed improved survival during subsequent exposure
      to 6 h of lethal anoxia (p<0.05 vs. non-preconditioned MSC[(non-PC)MSC]). In
      silico analysis and luciferase activity assay confirmed programmed cell death-10
      (PDCD10) as a putative target of miR-107 in (PC)MSC, which was significantly
      reduced during IPC and inversely related to stem cell survival under 6 h of
      lethal anoxia. Loss-of-function studies with miR-107 antagomir showed a
      significantly reduced survival of (PC)MSC. A comparison of miR-107 and miR-210
      showed that both miRs participated independently via their respective putative
      target genes Pdcd10 and Casp8ap2. The simultaneous abrogation of Pdcd10 and
      Casp8ap2 had a stronger effect on (PC)MSC survival under lethal anoxia. The
      transplantation of (PC)MSC in an acute model of myocardial infarction showed a
      significantly improved survival of transplanted (PC)MSC with concomitantly
      enhanced miR-107 expression in (PC)MSC-transplanted animal hearts. INNOVATION:
      Cytoprotection afforded by IPC is regulated by miR-107 induction via Pdcd10
      independent of miR-210/Casp8ap2 signaling, and the simultaneous abrogation miR
      107/miR-210 has a stronger effect on the loss of (PC)MSC survival. CONCLUSION:
      IPC enhances stem cell survival via the combined participation of hypoxia
      responsive miRs miR-107 and miR-210 via their respective putative target genes
      Pdcd10 and Casp8ap2.

PMID- 22482883
TI  - Development of biocompatible polymeric nanoparticles for in vivo NIR and FRET
      imaging.
AB  - The majority of near-infrared (NIR) fluorophores are organic molecules that show
      significant overlap between the excitation and emission spectra and therefore
      exhibit high fluorescence backgrounds during in vivo imaging. Recently, cyanine
      dyes with a large Stokes shift have shown great promise for NIR imaging but often
      undergo rapid photodegradation and nonspecific protein adsorption. Alternatively,
      fluorescence resonance energy transfer (FRET) is a promising technique to
      generate a larger gap between the excitation and emission maxima and thus can
      reduce the background signal. Here, we report the rational design of FRET-based
      polymeric nanoparticles for NIR and FRET imaging. The particles were assembled
      from diblock copolymers of poly(d,l-lactic-co-glycolic acid) and maleimide
      activated poly(ethylene glycol), which were also encapsulated with both the donor
      (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine) and acceptor (1,1'
      dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine) fluorophores. Because of
      their extreme hydrophobicity, thousands of fluorophores could be encapsulated
      inside a single particle without causing leakage. FRET resulted in a large Stokes
      shift (>100 nm) of the emission maxima, and the transfer efficiency could be fine
      tuned by further adjusting the doping ratio of the donor and acceptor
      fluorophores. The optimized formulation was less than 100 nm in size, brighter
      than quantum dots, stable in biological media, and demonstrated similar
      biodistribution to most nanomaterials. Additional animal phantom studies
      demonstrated that the FRET imaging platform developed could have far-reaching
      applications in optical imaging. 

PMID- 22482884
TI  - Cholinergic aspects of aging and Alzheimer's disease.

PMID- 22482885
TI  - Depressive symptoms and mild cognitive impairment in the elderly: an ominous
      combination.

PMID- 22482886
TI  - Is the idle mind a Devil's workshop?

PMID- 22482888
TI  - Dispersibility in water of dried nanocrystalline cellulose.
AB  - Dispersibility is important for nanocrystalline cellulose (NCC) because
      recovering the unique suspension and particle properties is essential after the
      product has been dried for storage or transport. It is our goal to produce dried
      NCC that redisperses in water to yield colloidal suspensions without the use of
      additives or a large energy input. In contrast with the as-prepared acidic form
      of NCC (H-NCC), suspensions of neutral sodium-form NCC (Na-NCC) dried by
      evaporation, lyophilization, or spray-drying are readily dispersible in water.
      Suspension properties and NCC particle size determined by light scattering were
      used as indicators of dispersion quality. The neutral counterion content, drying
      technique, freezing action, drying and redispersion concentrations, and moisture
      content in the dried NCC were all found to influence dispersibility. When a
      minimum of 94% of the H(+) counterion is exchanged for Na(+), the neutral salt
      form is fully dispersible in water even when fully dried. Mild sonication is
      generally sufficient to recover measured particle sizes identical to those in the
      never-dried Na-NCC sample. A threshold moisture content of 4 wt % was found,
      above which dried H-NCC is fully dispersible in water.

PMID- 22482889
TI  - Ionic nucleophilic catalysis of chiral ammonium betaines for highly
      stereoselective aldol reaction from oxindole-derived vinylic carbonates.
AB  - A new strategy for developing stereoselective bond-forming reactions is
      introduced; it takes advantage of the ionic nucleophilic catalysis of chiral
      ammonium betaines to utilize vinylic esters simultaneously as the enolate
      precursor and the acylating agent for coupling with electrophiles. Its synthetic
      utility is clearly demonstrated by the realization of a highly diastereo- and
      enantioselective aldol reaction from oxindole-derived vinylic carbonates.

PMID- 22482890
TI  - Peripheral functionalization of dendrimers regulates internalization and
      intracellular trafficking in living cells.
AB  - GATG (gallic acid-triethylene glycol) dendrimers represent appealing
      nanostructures for biomedical applications. The incorporation of specific ligands
      and targeting and imaging agents on their surface has resulted in promising tools
      in diagnosis and drug delivery. With the aim to further explore the versatility
      of GATG dendrimers in the biomedical field, in this work we study the effect of
      peripheral substitution on their uptake and intracellular trafficking in living
      cells. To this end, peripheral groups with different physicochemical properties
      and biological relevance have been installed on the surface of GATG dendrimers,
      and their interactions, uptake efficacy, and specificity for certain cell
      populations studied by confocal microscopy. Finally, this information was used to
      design a pH-sensitive drug delivery system for the selective release of cargo
      molecules inside cells after lysosomal localization. These results along with the
      easy functionalization and modular architecture of GATG dendrimers reveal these
      systems as promising nanotools in biomedicine. 

PMID- 22482892
TI  - [Ahmed versus Baerveldt shunts: which one is better?].

PMID- 22482891
TI  - Fanconi anemia links reactive oxygen species to insulin resistance and obesity.
AB  - AIMS: Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive
      oxygen species (ROS) have been proposed to play a causal role in insulin
      resistance. However, evidence linking ROS to insulin resistance in disease
      settings has been scant. Since both oxidative stress and diabetes have been
      observed in patients with the Fanconi anemia (FA), we sought to investigate the
      link between ROS and insulin resistance in this unique disease model. RESULTS:
      Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi
      anemia complementation group C (Fancc) gene seem to be diabetes-prone, as
      manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight
      gain when fed with a high-fat diet. These phenotypic features of insulin
      resistance are characterized by two critical events in insulin signaling: a
      reduction in tyrosine phosphorylation of the insulin receptor (IR) and an
      increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver,
      muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS,
      spontaneously accumulated or generated by tumor necrosis factor alpha in these
      insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin
      resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores
      IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally,
      pairwise screen identifies protein-tyrosine phosphatase (PTP)-alpha and stress
      kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS
      effect on FA insulin resistance. INNOVATION: These findings establish a
      pathogenic and mechanistic link between ROS and insulin resistance in a unique
      human disease setting. CONCLUSION: ROS accumulation contributes to the insulin
      resistance in FA deficiency by targeting both PTP-alpha and PKR.

PMID- 22482893
TI  - [Bacteriological analysis in the management of conjunctivitis. Comparison of
      antibiotic resistance between 1982 and 2008].
AB  - OBJECTIVE: To demonstrate the need for bacteriological analysis for the rational
      treatment of infections of the corneal surface, including conjunctivitis.
      METHODS: The results of 1,970 consecutive bacteriological analysis obtained from
      2001 to 2008 in patients with ocular hyperemia and discharge were analysed and
      compared with a similar study done in 1982 in the same geographical area.
      RESULTS: Bacterial growth was obtained in 1,044 cases (53%). The most frequent
      bacteria were Staphylococci spp. (56.6%), followed by Streptococci spp. (21.4%),
      Haemophili spp. (12.1%), and other gram-negative bacteria (9.9%). No antibiotic
      was effective against all the bacteria isolated. The frequency of resistant
      bacteria against neomycin, tobramycin, erythromycin and gentamicin was
      significantly increased with respect to the study of 1982. CONCLUSIONS:
      Bacteriological analysis of conjunctival specimens are necessary to ensure the
      choice of an effective antibiotic against bacteria of the ocular surface when the
      initial treatment fails.

PMID- 22482894
TI  - [Characteristics of patients with wet age-related macular degeneration and low
      intake of lutein and zeaxanthin].
AB  - OBJECTIVE: To assess the characteristics of patients with wet AMD and low intake
      of lutein and zeaxanthin in our population. METHODS: A prospective,
      observational, cross-sectional study was conducted on patients with active wet
      AMD. A full blood count, a lipid and liver profile, a dietary interview (24-hour
      recall), and an anthropometric study were performed. Lutein-zeaxanthin (LZ)
      intake results split the patents in two groups.Group 1 ("sufficient" intake):
      patients with >=1,400 mg/day intake in women and 1,700 mg/day in men (2/3 of the
      average daily intake in a normal population). Group 2: patients with daily
      intakes below that of group 1. A descriptive and comparative statistical study
      was performed. RESULTS: Fifty-two patients with a mean age of 78.9 years. Group
      1: eleven patients (21% of the sample). Group 2: forty-one patients. The subjects
      with adequate intake of LZ had higher a body mass index and waist circumference.
      Between 70-80% of patients in group 1 had inadequate intake of vitamin A, C and E
      and zinc. CONCLUSIONS: Seventy-nine per cent of the patients with wet AMD have a
      deficient daily intake in lutein-zeaxanthin. The population with adequate intake
      is associated with an increased body mass index and waist circumference, and in
      addition, most of them have an insufficient intake of vitamin A, C, E and zinc.

PMID- 22482895
TI  - [Immunohistochemical markers in the diagnosis of pigmented conjunctival lesions].
AB  - OBJECTIVE/METHOD: The aim of this study was to assess the importance of
      immunohistochemical markers in the diagnosis of pigmented conjunctival lesions.
      Due to the difficulty of making an exact clinical diagnosis, the suspicion of
      malignancy requires the removal of the lesion and performing a histopathology
      study in which immunohistochemical markers may help to determine the nature of
      the lesion. CASES REPORT/DISCUSSION: A case is presented of a 25 year-old woman
      with a pigmented lesion in the caruncle. It appeared recently and was growing
      fast with increasing pigmentation. Due to a suspicion of malignancy, the total
      lesion was removed. The microscopic study revealed cellular alterations which
      suggested malignancy. However, after carrying out immunohistochemical markers the
      diagnosis was conjunctival compound nevus.

PMID- 22482896
TI  - [Angle-closure glaucoma secondary to topiramate use].
AB  - CASE REPORT: We describe a 42 year-old patient who developed acute myopia and
      closed-angle glaucoma one week after beginning treatment with topiramate.
      Ultrasound biomicroscopy revealed a bilateral angle closure and choroidal
      effusion. The clinical findings resolved with withdrawal of the topiramate.
      DISCUSSION: Topiramate may cause acute myopia and closure angle glaucoma in some
      patients due to a choroidal effusion. Ultrasound biomicroscopy seems to be a
      useful tool for monitoring the progression of the clinical lesions and their
      resolution when the drug is withdrawn.

PMID- 22482897
TI  - [An enigmatic eye in an enigmatic bust].

PMID- 22482898
TI  - [Phototoxicity (3): Eye damage due to welder's arc].

PMID- 22482899
TI  - [Candido Mariano Da Silva Rondon: Santo Antonio do Leverger, Mimoso, Brazil
      (1865)-Rio de Janeiro, Brazil (1958)].

PMID- 22482900
TI  - Optimization and validation of a CE-LIF method for amino acid determination in
      biological samples.
AB  - There is increasing evidence that amino acids and related compounds are among the
      most important metabolites for living systems and their quantitative analysis is
      a continuous challenge for clinical and biochemical laboratories. The lack of
      chromophore group and their high polarity make the analytical process more
      difficult. A simple, rapid and inexpensive procedure based on CE-LIF has been
      optimised for biological samples such as urine and hippocampus tissue in terms of
      sample treatment, separation and quantitation. Around 30min were required for
      derivatization and determination by CE-LIF of l-alanine, l-aspartate, l-beta
      aminoisobutyrate, d-beta-aminoisobutyrate, glycine, l-glutamate, l-glutamine, l
      histidine, l-isoleucine, l-leucine, l-methionine, l-ornithine, l-phenylalanine, 4
      hydroxy-l-proline, l-proline, l-serine, d-serine, taurine, threonine and l
      valine. 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) is the labelling agent used
      for obtaining fluorescence derivatives stables in urine up to 12h and up to 24h
      in hippocampus extracts in refrigerated conditions. Electrophoretic conditions
      were: 90mM borate buffer at pH 10.25 prepared with 12.5mM native beta
      cyclodextrin. Applied voltage was +21kV. The method was validated for a
      representative group of amino acids in urine: l-phenylalanine, glycine, l-serine,
      d-serine and taurine. In hippocampus tissue the method was validated for the
      neurotransmitters: gamma-aminobutyric acid, l-glutamine, glycine, l-glutamate and
      l-aspartate. The method has been successfully applied to real samples, seven
      amino acids were quantified in 16 urine samples from healthy and type I diabetic
      children living in Spain, aged 8-11, and the results were statistically compared.
      They were in accordance to published reference values. Moreover neurotransmitters
      in hippocampus extracts were determined in samples of control mice and reported
      results were in accordance with previous references.

PMID- 22482901
TI  - Identification of the components of bitespiramycin by liquid chromatography-mass
      spectrometry.
AB  - Reversed-phase liquid chromatography coupled with electrospray ionization tandem
      mass spectrometry (LC/ESI-MS/MS) was used to characterize the components of
      bitespiramycin, a group of 4"-acylated spiramycins produced by bioengineered
      strains. In total 38 components were characterized in commercial samples,
      including 12 impurities that had never been reported before and 12 other that
      were partially characterized. The structures of these unknown compounds were
      deduced by comparison of their fragmentation patterns with those of known major
      components. Their ultraviolet spectra were used to confirm the presence of an
      alpha-, beta-, gamma-, delta-unsaturated butadiene in the macrocyclic lactone.
      Compared with the classical method, LC/ESI-MS/MS is particularly advantageous in
      terms of sensitivity and efficiency to characterize minor components at trace
      levels in multi-component antibiotics.

PMID- 22482902
TI  - Determination of eight amino acids in mice embryonic stem cells by pre-column
      derivatization HPLC with fluorescence detection.
AB  - A precise, accurate, and selective pre-column derivatization HPLC method with
      fluorescence detection was validated and used for the determination of amino
      acids (proline, valine, methionine, isoleucine, leucine, tryptophan,
      phenylalanine, and lysine) in mice embryonic stem (ES) cells. The cell sample was
      derivatized by dansyl chloride, and the analytes were separated on a C(18)
      column. The method provided good reproducibility and sensitivity for the
      quantification of the eight analytes with average recovery factors of less than
      107.43% and higher than 91.25%, respectively. Intra-day precision was between
      2.0% and 4.9%, and inter-day precision was between 2.9% and 6.0%. The %RSD values
      for repeatability were below 8.8. This assay can be readily utilized as a
      precise, sensitive, and highly accurate quality-control method for amino acids in
      mice ES cells.

PMID- 22482903
TI  - Isolation and structural elucidation of abietic acid as the main adulterant in an
      herbal drug for the treatment of psoriasis.
AB  - An herbal drug for the treatment of psoriasis showed severe clinical adverse
      reactions. The main component of adulterant was isolated from the drug and its
      chemical structure was elucidated as abietic acid using NMR, HR-MS, and HPLC-DAD
      MS. Although abietic acid had ever been used in clinical study for the treatment
      of psoriasis, it is not an approved drug. Its adulteration is very dangerous for
      the patients.

PMID- 22482904
TI  - The structural basis for control of eukaryotic protein kinases.
AB  - Eukaryotic protein kinases are key regulators of cell processes. Comparison of
      the structures of protein kinase domains, both alone and in complexes, allows
      generalizations to be made about the mechanisms that regulate protein kinase
      activation. Protein kinases in the active state adopt a catalytically competent
      conformation upon binding of both the ATP and peptide substrates that has led to
      an understanding of the catalytic mechanism. Docking sites remote from the
      catalytic site are a key feature of several substrate recognition complexes.
      Mechanisms for kinase activation through phosphorylation, additional domains or
      subunits, by scaffolding proteins and by kinase dimerization are discussed.

PMID- 22482905
TI  - Emerging paradigms for complex iron-sulfur cofactor assembly and insertion.
AB  - [FeFe]-hydrogenses and molybdenum (Mo)-nitrogenase are evolutionarily unrelated
      enzymes with unique complex iron-sulfur cofactors at their active sites. The H
      cluster of [FeFe]-hydrogenases and the FeMo cofactor of Mo-nitrogenase require
      specific maturation machinery for their proper synthesis and insertion into the
      structural enzymes. Recent insights reveal striking similarities in the
      biosynthetic pathways of these complex cofactors. For both systems, simple iron
      sulfur cluster precursors are modified on assembly scaffolds by the activity of
      radical S-adenosylmethionine (SAM) enzymes.   Radical SAM enzymes are responsible
      for the synthesis and insertion of the unique nonprotein ligands presumed to be
      key structural determinants for their respective catalytic activities. Maturation
      culminates in the transfer of the intact cluster assemblies to a cofactor-less
      structural protein recipient. Required roles for nucleotide binding and
      hydrolysis have been implicated in both systems, but the specific role for these
      requirements remain unclear. In this review, we highlight the progress on [FeFe]
      hydrogenase H cluster and nitrogenase FeMo-cofactor assembly in the context of
      these emerging paradigms.

PMID- 22482906
TI  - Regulation of glucose transporter translocation in health and diabetes.
AB  - To enhance glucose uptake into muscle and fat cells, insulin stimulates the
      translocation of GLUT4 glucose transporters from intracellular membranes to the
      cell surface. This response requires the intersection of insulin signaling and
      vesicle trafficking pathways, and it is compromised in the setting of
      overnutrition to cause insulin resistance. Insulin signals through AS160/Tbc1D4
      and Tbc1D1 to modulate Rab GTPases and through the Rho GTPase TC10alpha to act on
      other targets. In unstimulated cells, GLUT4 is incorporated into specialized
      storage vesicles containing IRAP, LRP1, sortilin, and VAMP2, which are
      sequestered by TUG, Ubc9, and other proteins. Insulin mobilizes these vesicles
      directly to the plasma membrane, and it modulates the trafficking itinerary so
      that cargo recycles from endosomes during ongoing insulin exposure. Knowledge of
      how signaling and trafficking pathways are coordinated will be essential to
      understanding the pathogenesis of diabetes and the metabolic syndrome and may
      also inform a wide range of other physiologies.

PMID- 22482907
TI  - Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions.
AB  - Ubiquitin acts as a versatile cellular signal that controls a wide range of
      biological processes including protein degradation, DNA repair, endocytosis,
      autophagy, transcription, immunity, and inflammation. The specificity of
      ubiquitin signaling is achieved by alternative conjugation signals (monoubiquitin
      and ubiquitin chains) and interactions with ubiquitin-binding proteins (known as
      ubiquitin receptors) that decode ubiquitinated target signals into biochemical
      cascades in the cell. Herein, we review the current knowledge pertaining to the
      structural and functional features of ubiquitin-binding proteins and the
      mechanisms by which they recognize various types of ubiquitin topologies. The
      combinatorial use of diverse ubiquitin-binding domains (UBDs) in full-length
      proteins, selective recognition of chains with distinct linkages and length, and
      posttranslational modifications of ubiquitin receptors or multivalent
      interactions within protein complexes illustrate a few mechanisms by which a
      circuitry of signaling networks can be rewired by ubiquitin-binding proteins to
      control cellular functions in vivo.

PMID- 22482909
TI  - Structure unifies the viral universe.
AB  - Is it possible to meaningfully comprehend the diversity of the viral world? We
      propose that it is. This is based on the observation that, although there is
      immense genomic variation, every infective virion is restricted by strict
      constraints in structure space (i.e., there are a limited number of ways to fold
      a protein chain, and only a small subset of these have the potential to construct
      a virion, the hallmark of a virus). We have previously suggested the use of
      structure for the higher-order classification of viruses, where genomic
      similarities are no longer observable. Here, we summarize the arguments behind
      this proposal, describe the current status of structural work, highlighting its
      power to infer common ancestry, and discuss the limitations and obstacles ahead
      of us. We also reflect on the future opportunities for a more concerted effort to
      provide high-throughput methods to facilitate the large-scale sampling of the
      virosphere.

PMID- 22482910
TI  - Receptor-mediated, tumor-targeted gene delivery using folate-terminated
      polyrotaxanes.
AB  - Safe and effective gene delivery is essential to the success of gene therapy. We
      synthesized and characterized a novel nonviral gene delivery system in which
      folate (FA) molecules were functioned as blockers on cationic polyrotaxanes (PR)
      composed of poly(ethylenimine) (PEI)(600)-grafted alpha-cyclodextrin rings
      linearized on polyethylene glycol to form FA-terminated PR-PEI(600) (FPP). The FA
      terminal caps of FPP target cell surfaces abundant in FA receptor (FR), a common
      feature of tumor cells. The structure of FPP was characterized by using (1)H
      nuclear magnetic resonance ((1)H NMR). The delivery particle was composed of
      chemically bonded PEG (4000), alpha-cyclodextrins (CD), and PEI (600 Da) at a
      molar ratio of 1:17:86.7, and the particle size and zeta potential of FPP/pDNA
      polyplexes were measured using dynamic light scattering. FPP/pDNA exhibited a
      lower cytotoxicity, strong specificity to FR, and high efficiency of delivering
      DNA to target cells in vitro and in vivo with the reporter genes. Furthermore,
      the FPP/DNA complex showed an enhanced antitumor effect in the nude mice compared
      with other delivery systems, such as PEI-25K. Together, these results suggest
      that FPP may be useful for gene therapy.

PMID- 22482908
TI  - The MPS1 family of protein kinases.
AB  - MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This
      family of potentially dual-specific protein kinases is among several that
      regulate a number of steps of mitosis. The most widely conserved MPS1 kinase
      functions involve activities at the kinetochore in both the chromosome attachment
      and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond
      mitosis, MPS1 kinases have been implicated in development, cytokinesis, and
      several different signaling pathways. Family members are identified by virtue of
      a conserved C-terminal kinase domain, though the N-terminal domain is quite
      divergent. The kinase domain of the human enzyme has been crystallized, revealing
      an unusual ATP-binding pocket. The activity, level, and subcellular localization
      of Mps1 family members are tightly regulated during cell-cycle progression. The
      mitotic functions of Mps1 kinases and their overexpression in some tumors have
      prompted the identification of Mps1 inhibitors and their active development as
      anticancer drugs.

PMID- 22482911
TI  - Contribution of PKMzeta-dependent and independent amplification to components of
      experimental neuropathic pain.
AB  - Injuries can induce adaptations in pain processing that result in amplification
      of signaling. One mechanism may be analogous to long-term potentiation and
      involve the atypical protein kinase C, PKMzeta. The possible contribution of
      PKMzeta-dependent and independent amplification mechanisms to experimental
      neuropathic pain was explored in rats with spinal nerve ligation (SNL) injury.
      SNL increased p-PKMzeta in the rostral anterior cingulate cortex (rACC), a site
      that mediates, in part, the unpleasant aspects of pain. Inhibition of PKMzeta
      within the rACC by a single administration of zeta-pseudosubstrate inhibitory
      peptide (ZIP) reversed SNL-induced aversiveness within 24 hours, whereas N-methyl
      d-aspartate receptor blockade with MK-801 had no effects. The SNL-induced
      aversive state (reflecting "spontaneous" pain), was re-established in a time
      dependent manner, with full recovery observed 7 days post-ZIP administration.
      Neither rACC ZIP nor MK-801 altered evoked responses. In contrast, spinal ZIP or
      MK-801, but not scrambled peptide, transiently reversed evoked hypersensitivity,
      but had no effect on nerve injury-induced spontaneous pain. PKMzeta
      phosphorylation was not altered by SNL in the spinal dorsal horn. These data
      suggest that amplification mechanisms contribute to different aspects of
      neuropathic pain at different levels of the neuraxis. Thus, PKMzeta-dependent
      amplification contributes to nerve injury-induced aversiveness within the rACC.
      Moreover, unlike mechanisms maintaining memory, the consequences of PKMzeta
      inhibition within the rACC are not permanent in neuropathic pain, possibly
      reflecting the re-establishment of amplification mechanisms by ongoing activity
      of injured nerves. In the spinal cord, however, both PKMzeta-dependent and
      independent mechanisms contribute to amplification of evoked responses, but
      apparently not spontaneous pain.

PMID- 22482912
TI  - Influences of bioavailability, trophic position, and growth on methylmercury in
      hakes (Merluccius merluccius) from Northwestern Mediterranean and Northeastern
      Atlantic.
AB  - Methylmercury (MeHg) determinations in hake, its food-chain, and the surrounding
      waters and sediments allowed us to show that the higher length or age normalized
      mercury concentrations of Northwestern Mediterranean (Gulf of Lions: GoL) muscle
      hakes compared to its Northeastern Atlantic (Bay of Biscay: BoB) counterpart are
      due to both biotic and abiotic differences between their ecosystems. Bioenergetic
      modeling reveals that the slower growth rate of Mediterranean hake favors the
      MeHg bioaccumulation in the fish muscle and explains most of the difference
      between GOL and BoB hake populations. In addition, the waters of the
      Mediterranean hake habitat favor a higher MeHg exposition, due to the upper
      position of the thermohalocline, where MeHg is formed. Furthermore, we show that,
      within the Mediterranean hake population, a major increase in the
      biomagnification power (the slope of the relationships between logMeHg and
      delta(15)N), from 0.36 up to 1.12, occurs when individuals enter adulthood,
      resulting from the combined effects of lowering growth rate and change in feeding
      habits. Finally, delta(15)N normalized Hg concentrations indicate that the
      highest Hg concentrations are for hake from the shelf edge and the lowest are for
      hake from the Rhone prodelta area, suggesting a lower Hg bioavailability in
      inshore environments, consistent with MeHg distributions in water, sediment, and
      preys.

PMID- 22482913
TI  - Applying a natural language processing tool to electronic health records to
      assess performance on colonoscopy quality measures.
AB  - BACKGROUND: Gastroenterology specialty societies have advocated that providers
      routinely assess their performance on colonoscopy quality measures. Such routine
      measurement has been hampered by the costs and time required to manually review
      colonoscopy and pathology reports. Natural language processing (NLP) is a field
      of computer science in which programs are trained to extract relevant information
      from text reports in an automated fashion. OBJECTIVE: To demonstrate the
      efficiency and potential of NLP-based colonoscopy quality measurement. DESIGN: In
      a cross-sectional study design, we used a previously validated NLP program to
      analyze colonoscopy reports and associated pathology notes. The resulting data
      were used to generate provider performance on colonoscopy quality measures.
      SETTING: Nine hospitals in the University of Pittsburgh Medical Center health
      care system. PATIENTS: Study sample consisted of the 24,157 colonoscopy reports
      and associated pathology reports from 2008 to 2009. MAIN OUTCOME MEASUREMENTS:
      Provider performance on 7 quality measures. RESULTS: Performance on the
      colonoscopy quality measures was generally poor, and there was a wide range of
      performance. For example, across hospitals, the adequacy of preparation was noted
      overall in only 45.7% of procedures (range 14.6%-86.1% across 9 hospitals), cecal
      landmarks were documented in 62.7% of procedures (range 11.6%-90.0%), and the
      adenoma detection rate was 25.2% (range 14.9%-33.9%). LIMITATIONS: Our quality
      assessment was limited to a single health care system in western Pennsylvania.
      CONCLUSIONS: Our study illustrates how NLP can mine free-text data in electronic
      records to measure and report on the quality of care. Even within a single
      academic hospital system, there is considerable variation in the performance on
      colonoscopy quality measures, demonstrating the need for better methods to
      regularly and efficiently assess quality.

PMID- 22482914
TI  - Endoscopic lumen restoration for obstructive aphagia: outcomes of a 25-year
      experience.
AB  - BACKGROUND: After chemoradiation therapy for head/neck cancer, some patients
      develop strictures that progress to complete pharyngoesophageal occlusion. Total
      lumen occlusion is less often due to other conditions. Enteral access
      (enterostomy tube) and good nutritional status tend to minimize the significance
      of dysphagia and therefore may mask recognition of impending complete lumen
      occlusion. OBJECTIVE: Review outcomes of a 25-year experience with endoscopic
      lumen restoration (ELR) in 30 patients. DESIGN: Retrospective, case review study.
      SETTING: Two tertiary-care referral centers. PATIENTS: This study involved 30
      consecutive patients referred for obstructive aphagia due to complete lumen
      occlusion, primarily after chemoradiation therapy for head/neck cancer.
      INTERVENTION: Antegrade and retrograde endoscopy with tri-plane fluoroscopy for
      penetrating the occluded segment, serial retrograde and antegrade dilations, plus
      swallowing rehabilitation therapy. MAIN OUTCOME MEASUREMENTS: Restoration of
      lumen patency, swallowing function, and removal of enteral feeding tube. RESULTS:
      ELR was successful in 30 patients in 31 of 33 attempts (93%). Return to soft to
      regular diet was achieved in 15 of 30 patients (50%), and fluids to pureed food
      with partial percutaneous endoscopic gastrostomy nutrition was achieved in 5 of
      30 patients (17%). Ten of 30 patients (33%) were considered unsafe for oral
      feeding because of oropharyngeal neuromotor deficits. Complications occurred in 5
      of 30 patients (17%), with no prolonged sequelae, deaths, or surgery, but two
      stents were placed for anastomotic fistulas. The median duration of follow-up was
      22.75 months. LIMITATIONS: Retrospective, case review study. CONCLUSION: ELR by
      using tri-plane fluoroscopic guidance with antegrade and retrograde endoscopy and
      serial dilations allows lumen restoration and swallowing to some degree in a
      majority of patients. Engagement of a core team of specialists can provide
      optimal restoration of swallowing function.

PMID- 22482915
TI  - Endoscopic submucosal dissection of early gastric neoplasia with a water jet
      assisted knife: a Western, single-center experience.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) of early gastric neoplasia has
      not yet been established in Western countries because of a lack of data and the
      difficult, time-consuming, and hazardous nature of the method. Some of the
      technical limitations may be overcome by use of a water jet-assisted knife, which
      allows a combination of a high-pressure water jet and electrosurgical
      interventions. OBJECTIVE: To evaluate the efficacy and safety of water jet
      assisted ESD (WESD) with a water jet-assisted knife in selected patients with
      early gastric neoplasia. DESIGN: Single-center, prospective study. PATIENTS: This
      study involved 29 consecutive patients (13 female; median age 61 years; age range
      35-93 years) with early gastric neoplasia that met the expanded criteria of the
      Japanese Gastric Cancer Association. Histology of biopsies had shown gastric
      adenocarcinoma in 21 cases, adenoma in 8 case, and suspicion of a GI stromal
      tumor in 1 case. The median maximal diameter of the lesions was 20 mm (range 10
      40 mm). INTERVENTION: All procedures were done with patients under sedation with
      propofol. The water jet-assisted knife was used for setting coagulation markers
      around the neoplastic lesions, then for circumferential incision and dissection
      in combination with repeated submucosal injection of saline solution with a water
      jet system. Bleeding was treated with diathermia by use of the water jet-assisted
      knife or hemostatic forceps in case of failure or larger vessels. Clips were used
      for closure of perforations. MAIN OUTCOME MEASUREMENTS: Complete resection of
      neoplasia, procedure time, complication and recurrence rates. RESULTS: According
      to endoscopic criteria, complete resection of the targeted area could be achieved
      in all cases, with an en bloc resection rate of 90%. The median procedure
      duration was 74 minutes (range 15-402 minutes). Exchange of the device was needed
      in only 10 cases because of severe bleeding from larger vessels, which could be
      managed by use of hemostatic forceps. The 30-day morbidity rate was 4 of 30
      (13.8%) because of postprocedure pain in 3 cases and delayed bleeding in 1 case.
      A 93-year-old patient died the night after WESD without evidence of a procedure
      related complication. Histology of the resected specimens showed adenocarcinoma
      in 20 cases, adenoma in 7, no neoplasia in 2, and a plasmacytoma in 1. Complete
      resection (R0) was histologically confirmed in 18 of 28 patients (64.3%) with
      resected neoplastic specimens. A horizontal or vertical neoplasia-free margin
      could not be confirmed in 9 cases and 1 case, respectively. Complete local
      remission of neoplasia was achieved in 25 of 28 patients (89.3%) who were
      followed over a median period of 22 months (range 6-44 months). In 1 patient, a
      metachronous gastric adenocarcinoma was identified 54 weeks after initial WESD.
      LIMITATIONS: Noncontrolled study with a limited number of patients. CONCLUSION:
      The use of a water jet-assisted knife simplifies ESD because exchange of devices
      is rarely needed. WESD promises to be effective and safe. The study demonstrates
      that the high rates of en bloc resection of early gastric neoplasia reported in
      Asia can be reproduced in Western referral centers. However, histology may not
      always confirm complete resection of horizontal tumor margins. In spite of the
      unfavorable histology results, the high rate of complete local remission of
      neoplasia promises that surgical treatment of early gastric neoplasia can be
      avoided in the majority of cases.

PMID- 22482916
TI  - Factors predicting perforation during endoscopic submucosal dissection for
      gastric cancer.
AB  - BACKGROUND: Perforation is a common complication of endoscopic submucosal
      dissection (ESD), but little is known about the relevant risk factors. OBJECTIVE:
      To investigate the risk factors for perforation. DESIGN: Retrospective study.
      SETTING: A cancer referral center. PATIENTS: A total of 1795 early gastric tumors
      in 1500 patients treated by ESD from July 2002 to December 2010 were included in
      the analysis. MAIN OUTCOME MEASUREMENTS: The associations between the incidence
      of perforation and patient and lesion characteristics were investigated. RESULTS:
      Perforation during ESD occurred in 50 lesions (2.8%). Univariate analysis
      identified tumor location (upper, middle, or lower stomach), tumor diameter (<=
      20 or >20 mm), and treatment period (lesions treated in the first or second
      period) as predictors of perforation. Multivariate analysis identified tumor
      location (upper stomach), tumor diameter (>20 mm), and treatment period (first
      half) as independent risk factors for perforation. The odds ratios were 2.4 (95%
      CI, 1.3-4.7; P = .006) for lesions in the upper stomach and 1.9 (95% CI, 1.0-3.5;
      P = .04) for lesions larger than 20 mm. Perforation risks were 5.4% for lesions
      in the upper stomach and 4.4% for lesions larger than 20 mm. Three patients
      required emergency surgery, but the rest of the patients were successfully
      treated with endoscopic clipping. There was no perforation-related mortality.
      LIMITATIONS: Single-center, retrospective study design. CONCLUSIONS: Lesions in
      the upper stomach and lesions larger than 20 mm were independent risk factors for
      perforation during ESD. Patients should be made aware of the estimated high risks
      of these lesions before undergoing ESD.

PMID- 22482917
TI  - Endoscopic appearance of proximal colorectal neoplasms and potential implications
      for colonoscopy in cancer prevention.
AB  - BACKGROUND: In everyday practice, the use of colonoscopy for the prevention of
      colorectal cancer (CRC) is less effective in the proximal than the distal colon.
      A potential explanation for this is that proximal neoplasms have a more subtle
      endoscopic appearance, making them more likely to be overlooked. OBJECTIVE: To
      investigate the differences in endoscopic appearance, ie, diminutive size and
      nonpolypoid shape, of proximal compared with distal colorectal neoplasms. DESIGN:
      Cross-sectional, single-center study. SETTING: Endoscopists at the Maastricht
      University Medical Center in the Netherlands who were previously trained in the
      detection and classification of nonpolypoid colorectal lesions. PATIENTS:
      Consecutive patients undergoing elective colonoscopy. MAIN OUTCOME MEASUREMENTS:
      Endoscopic appearance, ie, diminutive size (<6 mm) or nonpolypoid shape (height
      less than half of the diameter) of colorectal adenomas and serrated polyps (SPs),
      with a focus on adenomas with advanced histology, ie, high-grade dysplasia or
      early CRC and SPs with dysplasia or large size. RESULTS: We included 3720
      consecutive patients with 2106 adenomas and 941 SPs. We found that in both men
      and women, proximal adenomas with high-grade dysplasia/early CRC (n = 181) were
      more likely to be diminutive or nonpolypoid than distal ones (76.3% vs 26.2%;
      odds ratio [OR] 9.24; 95% CI, 4.45-19.2; P < .001). Of the proximal adenomas,
      84.4% were diminutive or nonpolypoid compared with 68.0% of the distal ones (OR
      2.66; 95% CI, 2.14-3.29; P < .001). Likewise, large/dysplastic SPs in the
      proximal colon were more often nonpolypoid than distal ones (66.2% vs 27.8%; OR
      5.51; 95% CI, 2.79-10.9; P < .001). LIMITATIONS: Inclusion of both symptomatic
      and asymptomatic patients. CONCLUSIONS: Proximal colorectal neoplasms with
      advanced histology frequently are small or have a nonpolypoid appearance. These
      findings support careful inspection of the proximal colon, if quality of cancer
      prevention with the use of colonoscopy is to be optimized.

PMID- 22482918
TI  - Comparison of partially covered nitinol stents with partially covered stainless
      stents as a historical control in a multicenter study of distal malignant biliary
      obstruction: the WATCH study.
AB  - BACKGROUND: Covered self-expandable metal stents (CSEMSs) were developed to
      prevent tumor ingrowth, but stent migration is one of the problems with CSEMSs.
      OBJECTIVE: To evaluate a new, commercially available CSEMS with flared ends and
      low axial force compared with a commercially available CSEMS without the anti
      migration system and high axial force. DESIGN: Multicenter, prospective study
      with a historical cohort. SETTING: Twenty Japanese referral centers. PATIENTS:
      This study involved patients with unresectable distal malignant biliary
      obstruction. INTERVENTION: Placement of a new, commercially available, partially
      covered SEMS. MAIN OUTCOME MEASUREMENTS: Recurrent biliary obstruction rate, time
      to recurrent biliary obstruction, stent-related complications, survival. RESULTS:
      Between April 2009 and March 2010, 141 patients underwent partially covered
      nitinol stent placement, and between May 2001 and January 2007, 138 patients
      underwent placement of partially covered stainless stents as a historical
      control. The silicone cover of the partially covered nitinol stents prevented
      tumor ingrowth. There were no significant differences in survival (229 vs 219
      days; P = .250) or the rate of recurrent biliary obstruction (33% vs 38%; P =
      .385) between partially covered nitinol stents and partially covered stainless
      stents. Stent migration was less frequent (8% vs 17%; P = .019), and time to
      recurrent biliary obstruction was significantly longer (373 vs 285 days; P =
      .007) with partially covered nitinol stents. Stent removal was successful in 26
      of 27 patients (96%). LIMITATIONS: Nonrandomized, controlled trial. CONCLUSION:
      Partially covered nitinol stents with an anti-migration system and less axial
      force demonstrated longer time to recurrent biliary obstruction with no tumor
      ingrowth and less stent migration.

PMID- 22482919
TI  - Successful treatment of diffuse esophageal spasm by peroral endoscopic myotomy.

PMID- 22482921
TI  - High mortality of cocaine-related ischemic colitis: a hybrid cohort/case-control
      study.
AB  - BACKGROUND: Isolated case reports describe bowel ischemia in cocaine users, and
      the optimal management of these patients remains uncertain. DESIGN: Case-control
      study. SETTING: Teaching hospitals. PATIENTS: Patients hospitalized for colonic
      ischemia related to cocaine compared with noncocaine-related ischemic colitis.
      Cases were identified by using ICD-9 codes and laboratory urine toxicology tests.
      Patients were included if they had a confirmed diagnosis of bowel ischemia by CT,
      colonoscopy, angiography, or, in the case of emergency exploration, a pathology
      report showing bowel ischemia and a urine toxicology test that was positive for
      cocaine. Controls were individuals who met the same criteria but had no history
      of cocaine use and a urine test negative for cocaine. Charts were individually
      audited for accuracy of coding. MAIN OUTCOME MEASUREMENTS: Mortality and its risk
      factors. RESULTS: Patients with cocaine-related ischemia were significantly
      younger and had a significantly (P < .05) higher mortality rate than patients
      with ischemic colitis unrelated to cocaine (cocaine: 5/19 [26%] and noncocaine:
      6/78 [7.7%]). The cause of death in all cases was septic shock caused by
      extensive bowel ischemia. Multivariate logistic regression analysis showed that
      cocaine-related ischemic colitis was a significant risk factor for mortality
      (odds ratio 5.77; 95% CI, 1.37-24.39) as was the need for surgical intervention
      (odds ratio 4.95; 95% CI, 1.22-20.12). LIMITATIONS: Retrospective design.
      CONCLUSIONS: Cocaine-related ischemic colitis has a high mortality. In young
      patients presenting with acute abdominal pain and/or rectal bleeding with
      evidence of bowel wall thickening or pneumatosis on imaging studies or
      colonoscopy, cocaine-related ischemia should be considered. Testing for cocaine
      use may help identify patients at high risk of sepsis and death.

PMID- 22482920
TI  - Characterization of buried glands before and after radiofrequency ablation by
      using 3-dimensional optical coherence tomography (with videos).
AB  - BACKGROUND: Radiofrequency ablation (RFA) is an endoscopic technique used to
      eradicate Barrett's esophagus (BE). However, such ablation can commonly lead to
      neosquamous epithelium overlying residual BE glands not visible by conventional
      endoscopy and may evade detection on random biopsy samples. OBJECTIVE: To
      demonstrate the capability of endoscopic 3-dimensional optical coherence
      tomography (3D-OCT) for the identification and characterization of buried glands
      before and after RFA therapy. DESIGN: Cross-sectional study. SETTING: Single
      teaching hospital. PATIENTS: Twenty-six male and 1 female white patients with BE
      undergoing RFA treatment. INTERVENTIONS: 3D-OCT was performed at the
      gastroesophageal junction in 18 patients before attaining complete eradication of
      intestinal metaplasia (pre-CE-IM group) and in 16 patients after CE-IM (post-CE
      IM group). MAIN OUTCOME MEASUREMENTS: Prevalence, size, and location of buried
      glands relative to the squamocolumnar junction. RESULTS: 3D-OCT provided an
      approximately 30 to 60 times larger field of view compared with jumbo and
      standard biopsy and sufficient imaging depth for detecting buried glands. Based
      on 3D-OCT results, buried glands were found in 72% of patients (13/18) in the pre
      CE-IM group and 63% of patients (10/16) in the post-CE-IM group. The number (mean
      [standard deviation]) of buried glands per patient in the post-CE-IM group (7.1
      [9.3]) was significantly lower compared with the pre-CE-IM group (34.4 [44.6]; P
      = .02). The buried gland size (P = .69) and distribution (P = .54) were not
      significantly different before and after CE-IM. LIMITATIONS: A single-center,
      cross-sectional study comparing patients at different time points in treatment.
      Lack of 1-to-1 coregistered histology for all OCT data sets obtained in vivo.
      CONCLUSION: Buried glands were frequently detected with 3D-OCT near the
      gastroesophageal junction before and after radiofrequency ablation.

PMID- 22482922
TI  - Colon cancer with gastric invasion mimicking gastric submucosal tumor.

PMID- 22482923
TI  - Use of the endoscopically applied hemostatic powder TC-325 in cancer-related
      upper GI hemorrhage: preliminary experience (with video).

PMID- 22482924
TI  - Sulcal morphology and volume of Broca's area linked to handedness and sex.
AB  - We investigated the effect of handedness and sex on: (i) sulcal contours defining
      PO and PTR and (ii) volume estimates of PO and PTR subfields in 40 left- and 42
      right-handers. Results show an effect of handedness on discontinuity of the
      inferior frontal sulcus (IFS: P<0.01). Discontinuity of IFS was observed in: 43%
      left- and 62% right hemispheres in right-handers and in 65% left- and 48% right
      hemispheres in left-handers. PO volume asymmetry was rightward in left-handed
      males (P=0.007) and females (P=0.02), showed a leftward trend in right-handed
      males (P=0.06), and was non-asymmetrical in right-handed females (P=0.96, i.e.
      left- and right-hemisphere PO volumes did not differ significantly). PO volume
      asymmetry in males differed significantly between handedness groups (P=0.001).
      Findings indicate a high degree of variability in the sulcal contours of PO and
      PTR and volume asymmetry of PO: the factors sex and handedness can explain some
      of this variability.

PMID- 22482925
TI  - Endoscopic endonasal extended transsphenoidal removal of tuberculum sellae
      meningioma (TSM): an experience of six cases.
AB  - AIMS: Tuberculum sellae meningiomas (TSMs) are usually removed through a
      transcranial approach. Recently, the sublabial transsphenoidal microscopic
      approach has been used to remove such tumours. More recently, endonasal extended
      transsphenoidal approach is getting popular for removal of tuberculum sellae
      meningioma. Here, we describe our initial experience of endonasal extended
      transsphenoidal approach for removal of suprasellar meningiomas in six
      consecutive cases. MATERIALS AND METHOD: Six patients (four female and two male)
      who presented for headache and visual loss were investigated with MRI of brain
      that showed tuberculum sellae meningioma compressing visual apparatus. Average
      size was 3 * 3 cm in three cases and 4 * 4 cm in rest of the three. All patients
      underwent endoscopic endonasal extended transsphenoidal tumour removal, but in
      two patients with large tumour, microscopic assistance was needed. Complete
      tumour removal was done in all cases except one case where perforators seemed to
      be encased by the tumour and resulted in incomplete removal. The surgical dural
      and bony defects were repaired in all patients with thigh fat graft. Nasal
      packing was not used, but inflated balloon of Foley's catheter was used to keep
      fat in position. RESULT: There was mild postoperative cerebrospinal fluid (CSF)
      leakage in one patient on the fourth postoperative day after removal of lumbar
      CSF drain and stopped spontaneously on the seventh postoperative day. There were
      no postoperative CSF leaks or meningitis in the rest of the cases. In one
      patient, there was visual deterioration due to pressure on optic nerve by grafted
      fat and improved within 4 weeks. At 4 months after surgery, three patients had
      normal vision, two patients improved vision comparing with that of preoperative
      state but with some persisting deficit; one patient had static vision, no new
      endocrinopathy and no residual tumour on MRI in five cases but residual tumour in
      remaining case was static at the end of the ninth month. CONCLUSION: The
      endoscopic endonasal extended transsphenoidal approach appears to be an effective
      minimally invasive method for removing relatively small to medium tuberculum
      sellae meningiomas. With more experience of the surgeon, larger tuberculum sellae
      meningioma may be removed by purely endoscopic techniques in near future.

PMID- 22482926
TI  - NICE guidance on the use of carmustine wafers in high grade gliomas: a national
      study on variation in practice.
AB  - BACKGROUND: Multidisciplinary team (MDT) working in oncology aims to improve
      outcomes for patients with cancer. One role is to ensure the implementation of
      best practice and National Institute for Health and Clinical Excellence (NICE)
      guidance. In this study, we have assessed the role of MDT in implementing the
      TA121 appraisal of the use of carmustine wafers in high grade gliomas. METHODS:
      296 patients with high-grade glioma suitable for maximal resection were recruited
      from 17 Neurosurgical Centres. The number of patients treated with carmustine
      wafers and reasons for not using this were recorded. Complications at 48 hours
      post-operatively and at 6 weeks post-radiotherapy were recorded. RESULTS: 94/296
      (32%) of suitable patients received carmustine wafers. In 55% of cases carmustine
      was not used due to either surgeon preference or a lack of an MDT decision. There
      was no increased complication rate with carmustine use at either 48 hours post
      surgery or at 6 weeks post radiotherapy. Use of carmustine wafers did not
      decrease access to and use of chemoradiotherapy. CONCLUSIONS: One third of
      patients suitable for carmustine wafers received them. Their use was neither
      associated with more frequent complications, nor decreased use of
      chemoradiotherapy. Implementation of NICE TA121 Guidance is extremely variable in
      different MDTs across the United Kingdom.

PMID- 22482927
TI  - Luminal lipid phases after administration of a triglyceride solution of danazol
      in the fed state and their contribution to the flux of danazol across Caco-2 cell
      monolayers.
AB  - The first aim of this study was to characterize the luminal contents and their
      micellar phase after the administration of a heterogeneous liquid meal to healthy
      adults. The second aim was to evaluate the impact of micellar lipids and coarse
      lipid particles on danazol flux through intestinal monolayers. A third aim was to
      compare the micellar composition in the upper small intestine with the
      composition of fed state simulating intestinal fluid (FeSSIF-V2), a medium that
      has been proposed for investigating dissolution of poorly soluble drugs in the
      fed state. Danazol (150 mg), predissolved in the olive oil portion of the meal,
      was administered via the gastric port of a two-lumen tube to the antrum of eight
      adults. Aspirates from the ligament of Treitz [collected up to 4 h postdosing
      (~15 mL every 30 min)] were characterized physicochemically. Comparison of these
      characteristics with FeSSIF-V2 indicates that FeSSIF-V2 is an appropriate medium
      for evaluating drug solubilization in the luminal micellar phase in the fed
      state. Individual aspirates and their corresponding micellar phases were also
      diluted with aqueous transport medium and subjected to Caco-2 cell permeation
      experiments. Permeability coefficients for danazol in the diluted aspirates were
      smaller than those for the diluted micellar phases, which in turn were similar to
      those for aqueous transport medium. The high danazol concentrations
      overcompensated the reduced permeability coefficient values in the diluted
      aspirates in terms of total drug flux. We conclude that drug dissolved in the
      coarse lipid particles formed after administration of a triglyceride solution can
      directly contribute to the flux of lipophilic drugs across the intestinal mucosa.

PMID- 22482928
TI  - Vapor-solid growth of few-layer graphene using radio frequency sputtering
      deposition and its application on field emission.
AB  - The carbon nanotube (CNT) and graphene hybrid is an attractive candidate for
      field emission (FE) because of its unique properties, such as high conductivity,
      large aspect ratio of CNT, and numerous sharp edges of graphene. We report here a
      vapor-solid growth of few-layer graphene (FLG, less than 10 layers) on CNTs
      (FLG/CNT) and Si wafers using a radio frequency sputtering deposition system.
      Based on SEM, TEM, and Raman spectrum analyses, a defect nucleation mechanism of
      the FLG growth was proposed. The FE measurements indicate that the FLG/CNT
      hybrids have low turn-on (0.956 V/MUm) and threshold fields (1.497 V/MUm), large
      field enhancement factor (~4398), and good stability. Excellent FE properties of
      the FLG/CNT hybrids make them attractive candidates as high-performance field
      emitters.

PMID- 22482929
TI  - In vivo and in vitro efficacy of sainfoin (Onobrychis viciifolia) against Eimeria
      spp in lambs.
AB  - The effect of sainfoin (Onobrychis viciifolia) against ovine coccidia was
      evaluated in vivo and in vitro. In 3 in vivo trials weaned lambs were allocated
      into two treatment groups receiving diets with either lucerne (Medicago sativa)
      or sainfoin. During the trials, which lasted for 7 (trial 1) or 8 weeks (trials 2
      and 3), oocysts per gram of faeces (OPGs), faecal scores and weight gain were
      recorded. In two of the experiments (trials 1 and 3) a reduction in the mean
      oocyst excretion rates was observed, starting three to four weeks after sainfoin
      hay feeding. This reduction ranged between 21.3% (trial 1) and 61.7% (trial 3)
      compared to the control values. As a result, a decrease in the total number of
      oocysts excreted (expressed as the mean area under the curve of the OPG) was
      observed from week 4 to the end of the two trials, respectively (trial 1: 42.6%
      reduction, p=0.05; trial 3: 52.4% reduction, p=0.06). The results did not show
      any significant diet effect on lamb growth rates and faecal scores. In the in
      vitro experiments the effect of 39 sainfoin extracts were tested in an oocyst
      sporulation inhibition assay. The Eimeria oocysts sporulation inhibition
      throughout the experiments did not exceed 10.7%, showing that extracts of this
      forages do not have a significant inhibitory effect on Eimeria oocyst
      sporulation. This was an initial attempt to investigate a possible anticoccidial
      effect of sainfoin and further studies are needed in order to better understand
      its mode of action against Eimeria.

PMID- 22482930
TI  - The dissolution rates of SiO2 nanoparticles as a function of particle size.
AB  - There is a critical need to better define the relationship among particle size,
      surface area, and dissolution rate for nanoscale materials to determine their
      role in the environment, their toxicity, and their technological utility.
      Although some previous studies concluded that nanoparticles dissolve faster than
      their bulk analogs, contradictory evidence suggests that nanoparticles dissolve
      more slowly. Furthermore, insufficient characterization of the nanoparticulate
      samples and the solution chemistry in past studies obscures the relationship
      between particle size, surface area, and dissolution rate. Here we report
      amorphous SiO(2) dissolution rates in aqueous solutions determined from
      complementary mixed-flow and closed reactor experiments at 6.9 >= pH >= 11.2 and
      25  degrees C as a function of particle diameter from 25 to 177 nm. Experiments
      were performed at far-from-equilibrium conditions to isolate kinetic effects from
      those of changing the reaction driving force on overall dissolution rates.
      Measured far-from-equilibrium mass normalized dissolution rates are nearly
      independent of particle size, but corresponding BET surface area normalized rates
      decrease substantially with decreasing particle size. Combining these
      observations with existing established kinetic rate equations allows the
      prediction of nanoparticle dissolution rates as a function of both particle size
      and aqueous fluid saturation state.

PMID- 22482931
TI  - Biomechanical analysis of second-generation headless compression screws.
AB  - INTRODUCTION: Headless Compression Screws (HCS) are commonly utilized for the
      fixation of small bone and articular fractures. Recently several new second
      generation HCS (SG-HCS) have been introduced with the purported benefits of
      improved biomechanical characteristics. We sought to determine and compare the
      biomechanical efficiencies of these screws. MATERIAL AND METHODS: Five HCS
      including four second generation (Mini-Acutrak 2 (Acumed), Twinfix (Stryker),
      Kompressor Mini (Integra), HCS 3.0 (Synthes)) and one first generation (Herbert
      Whipple) were studied. Polyurethane foam blocks that represented osteoporotic
      cancellous bone (0.16 g/cc) with a simulated transverse fracture at the waist
      were utilized and five screws of each brand were tested for the generated
      compression force and fastening torque during insertion with and without pre
      drilling. RESULTS: The generated compression force was highest for Mini-Acutrak 2
      (45.41 +/- 0.88 N) and lowest for Herbert-Whipple (13.44 +/- 2.35 N) and forces
      of Twinfix, Kompressor Mini, HCS 3.0 were in between in descending order. The
      compression force of SG-HCS increased slightly without pre-drilling but it was
      not statistically significant while the fastening torque increased significantly.
      Slight over-fastening beyond the recommended stage significantly reduced the
      compression force in Twinfix and Kompressor and had no or moderate effect in
      other screws. CONCLUSION: All SG-HCS demonstrated greater biomechanical
      characteristics than the first generation Herbert-Whipple screw. The Mini-Acutrak
      2 with a variable pitch design generated the maximum compression force and showed
      the most reliability and sustainability. Screws with independently rotating
      trailing heads (Twinfix and Kompressor Mini) demonstrated loss of compression
      with extra turns. The increase of fastening torque due to over-fastening and loss
      of compression at the same time in some screw designs, demonstrated how the
      fastening torque (applied by the surgeon) can be a misleading measure of the
      compression force. Application of SG-HCS in osteoporotic bone without pre
      drilling can slightly increase the compression force.

PMID- 22482932
TI  - Identity, intimacy, status and sex dating goals as correlates of goal-consistent
      behavior and satisfaction in Australian youth.
AB  - The most common dating goals of adolescents are identity, intimacy, status and
      sex. In this study of Australian youth (16-30 years, N = 208), dating goals were
      expected to explain goal-consistent behavior in each domain. Also, goals coupled
      with consistent behavior were expected to be associated with greater satisfaction
      in each domain. Age, gender, same-sex versus other-sex attraction, and
      cohabitation were also examined. The four dating goals had small
      intercorrelations, and for each domain but sex, youth who reported more of a
      dating goal also reported more goal-consistent behavior. For identity, intimacy
      and sex, participants were more satisfied when they had more goal-consistent
      behavior. Goal * Behavior interactions were associated with satisfaction in the
      domains of intimacy and sex, and identity was the most salient dating goal
      domain. Individual differences in goals, behavior and satisfaction were most
      pronounced for gender and cohabitation. Few differences were found between same
      sex and other-sex attracted youth.

PMID- 22482933
TI  - Are the differences in treatment outcome for adenocarcinoma of the cervix
      different enough to change the treatment paradigm?

PMID- 22482934
TI  - [Clinical characterization of prostate cancer potentially insignificant in the
      prostate biopsy].
AB  - OBJECTIVE: The aim of this study was to identify the rate of clinical significant
      disease (Gleason score>6 or tumor volume>0.5 cc in the RP specimen) among
      patients who had an insignificant prostate cancer on biopsy, evaluating the
      presence of prognostic factors. PATIENTS AND METHODS: Patients who fulfilled the
      following criteria were included: PSA <= 10ng/ml, T1c disease, biopsy Gleason
      Score <= 6 affecting <5% of only 1 core and who had undergone a radical
      prostatectomy. The following variables were studied: Age, PSA, dPSA, free/total
      PSA ratio and prostatic volume assessed by transrectal ultrasound. RESULTS: In a
      series of 2424 biopsies, 77 patients completely fulfilled the inclusion criteria,
      with 66.23% (n=51) of clinical significant disease in the prostatectomy specimen.
      No differences were observed between these patients and those with insignificant
      disease in age, PSA, free/total PSA ratio. However, prostatic volume was
      significantly greater and PSA density significantly lower in those patients with
      an insignificant disease. Statistical analysis using a logistical regression
      showed that dPSA was the only prognostic factor (OR: 25067.10, CI 95%: 26.79
      2.34*10(7), P=.004). CONCLUSIONS: These findings suggest that a high rate of
      patients who have a suspected insignificant prostate cancer on biopsy have a
      clinical significant disease, being dPSA the only independent prognostic factor.

PMID- 22482935
TI  - Phase separation behavior of fusidic acid and rifampicin in PLGA microspheres.
AB  - The purpose of this study was to characterize the phase separation behavior of
      fusidic acid (FA) and rifampicin (RIF) in poly(d,l-lactic acid-co-glycolic acid)
      (PLGA) using a model microsphere formulation. To accomplish this, microspheres
      containing 20% FA with 0%, 5%, 10%, 20%, and 30% RIF and 20% RIF with 30%, 20%
      10%, 5%, and 0% FA were prepared by solvent evaporation. Drug-polymer and drug
      drug compatibility and miscibility were characterized using laser confocal
      microscopy, Raman spectroscopy, XRPD, DSC, and real-time video recordings of
      single-microsphere formation. The encapsulation of FA and RIF alone, or in
      combination, results in a liquid-liquid phase separation of solvent-and-drug-rich
      microdomains that are excluded from the polymer bulk during microsphere
      hardening, resulting in amorphous spherical drug-rich domains within the polymer
      bulk and on the microsphere surface. FA and RIF phase separate from PLGA at
      relative droplet volumes of 0.311 +/- 0.014 and 0.194 +/- 0.000, respectively,
      predictive of the incompatibility of each drug and PLGA. When coloaded, FA and
      RIF phase separate in a single event at the relative droplet volume 0.251 +/-
      0.002, intermediate between each of the monoloaded formulations and dependent on
      the relative contribution of FA or RIF. The release of FA and RIF from phase
      separated microspheres was characterized exclusively by a burst release and was
      dependent on the phase exclusion of surface drug-rich domains. Phase separation
      results in coalescence of drug-rich microdroplets and polymer phase exclusion,
      and it is dependent on the compatibility between FA and RIF and PLGA. FA and RIF
      are mutually miscible in all proportions as an amorphous glass, and they phase
      separate from the polymer as such. These drug-rich domains were excluded to the
      surface of the microspheres, and subsequent release of both drugs from the
      microspheres was rapid and reflected this surface location.

PMID- 22482936
TI  - Hands on, hands off? The swings in musculoskeletal physiotherapy practice.

PMID- 22482937
TI  - Nanotextured silica surfaces with robust superhydrophobicity and omnidirectional
      broadband supertransmissivity.
AB  - Designing multifunctional surfaces that have user-specified interactions with
      impacting liquids and with incident light is a topic of both fundamental and
      practical significance. Taking cues from nature, we use tapered conical
      nanotextures to fabricate the multifunctional surfaces; the slender conical
      features result in large topographic roughness, while the axial gradient in the
      effective refractive index minimizes reflection through adiabatic index-matching
      between air and the substrate. Precise geometric control of the conical shape and
      slenderness of the features as well as periodicity at the nanoscale are all keys
      to optimizing the multifunctionality of the textured surface, but at the same
      time, these demands pose the toughest fabrication challenges. Here we report a
      systematic approach to concurrent design of optimal structures in the fluidic and
      optical domains and a fabrication procedure that achieves the desired aspect
      ratios and periodicities with few defects and large pattern area. Our fabricated
      nanostructures demonstrate structural superhydrophilicity or, in combination with
      a suitable chemical coating, robust superhydrophobicity. Enhanced polarization
      independent optical transmission exceeding 98% has also been achieved over a
      broad range of bandwidth and incident angles. These nanotextured surfaces are
      also robustly antifogging or self-cleaning, offering potential benefits for
      applications such as photovoltaic solar cells.

PMID- 22482938
TI  - Antiresorptive treatment options and bone health in cancer patients-safety
      profiles and clinical considerations.
AB  - Antiresorptive therapies are the standard of care for maintaining bone health in
      patients with advanced cancers involving bone. In the absence of antiresorptive
      therapies, many patients with bone metastases from solid tumors will experience
      potentially debilitating skeletal-related events. Furthermore, older age is
      associated with decreased bone integrity both in female and male patients and
      also with increased risk for malignancies, such as breast and prostate cancer,
      which have a high risk of metastasis to bone. Although antiresorptive therapies
      are generally well tolerated, there have been reports of associated serious
      adverse events. Hypocalcemia, osteonecrosis of the jaw, renal events, and acute
      phase reactions have been reported in patients with cancer receiving all types of
      antiresorptive therapies. Because the clinical indications of antiresorptive
      agents continue to expand, and new options are becoming available, it is
      important for clinicians to recognize adverse events so that they may be
      prevented or properly treated and managed. Moreover, the risk-benefit profiles of
      those agents must be considered on a per-patient basis.

PMID- 22482939
TI  - Mitochondrial diseases.
AB  - Mitochondria have a crucial role in cellular bioenergetics and apoptosis, and
      thus are important to support cell function and in determination of cell death
      pathways. Inherited mitochondrial diseases can be caused by mutations of
      mitochondrial DNA or of nuclear genes that encode mitochondrial proteins.
      Although many mitochondrial disorders are multisystemic, some are tissue specific
      -eg, optic neuropathy, sensorineural deafness, and type 2 diabetes mellitus. In
      the past few years, several disorders have been associated with mutations of
      nuclear genes responsible for mitochondrial DNA maintenance and function, and the
      potential contribution of mitochondrial abnormalities to progressive
      neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease
      has been recognised. The process of mitochondrial fission-fusion has become a
      focus of attention in human disease. Importantly, the mitochondrion is now a
      target for therapeutic interventions that encompass small molecules,
      transcriptional regulation, and genetic manipulation, offering opportunities to
      treat a diverse range of diseases.

PMID- 22482941
TI  - Treatment of AML: resurrection for gemtuzumab ozogamicin?

PMID- 22482942
TI  - Dark oxidation of dissolved gaseous mercury in polar ice mimics.
AB  - The low-temperature chemistry associated with environmentally available mercury
      has recently attracted considerable scientific interest due to the discovery of
      systemic gas-phase mercury depletion events (MDEs) which occur periodically at
      the poles. However, the fate of the mercury once it enters the snowpack is not
      fully understood, even its chemical speciation has yet to be well characterized.
      An issue that is of particular concern in frozen environments is the
      transformation of elemental mercury (Hg(0)) to more bioavailable oxidized forms,
      which can then be methylated by biotic and abiotic processes. The resulting
      methyl mercury species produced can bioaccumulate through the food chain and the
      health effects of this on humans and mammals have been well-documented. During
      the current study, a novel set of "freeze-induced" pathways, which can
      potentially affect the reactivity of dissolved gaseous mercury (DGM) were
      followed. The experiments were performed using environmentally relevant cosolutes
      at appropriate concentration levels and temperatures. Evidence is thereby
      presented that due to rate accelerations associated with the operation of the
      freeze-concentration effect, DGM is oxidized to Hg(2+) ions when frozen in the
      presence of a variety of materials including hydrogen peroxide, nitrous acid and
      the sulfuric acid/O(2) couple.

PMID- 22482940
TI  - Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute
      myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study.
AB  - BACKGROUND: The results of the addition of gemtuzumab ozogamicin, an anti-CD33
      antibody conjugate, to the standard treatment for patients with acute myeloid
      leukaemia in phase 3 trials were contradictory. We investigated whether the
      addition of low fractionated-dose gemtuzumab ozogamicin to standard front-line
      chemotherapy would improve the outcome of patients with this leukaemia without
      causing excessive toxicity. METHODS: In a phase 3, open-label study, undertaken
      in 26 haematology centres in France, patients aged 50-70 years with previously
      untreated de novo acute myeloid leukaemia were randomly assigned with a computer
      generated sequence in a 1:1 ratio with block sizes of four to standard treatment
      (control group) with or without five doses of intravenous gemtuzumab ozogamicin
      (3 mg/m(2) on days 1, 4, and 7 during induction and day 1 of each of the two
      consolidation chemotherapy courses). The primary endpoint was event-free survival
      (EFS). Secondary endpoints were relapse-free (RFS), overall survival (OS), and
      safety. Analysis was by intention to treat. This study is registered with
      EudraCT, number 2007-002933-36. FINDINGS: 280 patients were randomly assigned to
      the control (n=140) and gemtuzumab ozogamicin groups (n=140), and 139 patients
      were analysed in each group. Complete response with or without incomplete
      platelet recovery to induction was 104 (75%) in the control group and 113 (81%)
      in the gemtuzumab ozogamicin group (odds ratio 1.46, 95% CI 0.20-2.59; p=0.25).
      At 2 years, EFS was estimated as 17.1% (10.8-27.1) in the control group versus
      40.8% (32.8-50.8) in the gemtuzumab ozogamicin group (hazard ratio 0.58, 0.43
      0.78; p=0.0003), OS 41.9% (33.1-53.1) versus 53.2% (44.6-63.5), respectively
      (0.69, 0.49-0.98; p=0.0368), and RFS 22.7% (14.5-35.7) versus 50.3% (41.0-61.6),
      respectively (0.52, 0.36-0.75; p=0.0003). Haematological toxicity, particularly
      persistent thrombocytopenia, was more common in the gemtuzumab ozogamicin group
      than in the control group (22 [16%] vs 4 [3%]; p<0.0001), without an increase in
      the risk of death from toxicity. INTERPRETATION: The use of fractionated lower
      doses of gemtuzumab ozogamicin allows the safe delivery of higher cumulative
      doses and substantially improves outcomes in patients with acute myeloid
      leukaemia. The findings warrant reassessment of gemtuzumab ozogamicin as front
      line therapy for acute myeloid leukaemia. FUNDING: Wyeth (Pfizer).

PMID- 22482943
TI  - Principles of model building: an experimentation-aided approach to development of
      models for signaling networks.
AB  - Living cells continuously probe their environment and respond to a multitude of
      external cues. The information about the environment is carried by signaling
      cascades that act as "internal transducing and computing modules," coupled into
      complex and interconnected networks. A comprehensive understanding of how cells
      make decisions therefore necessitates a sound theoretical framework, which can be
      achieved through mathematical modeling of the signaling networks. In this
      chapter, we conceptually describe the typical workflow involved in building
      mathematical models that are motivated by and are developed in a tight
      integration with experimental analysis. In particular, we delineate the steps
      involved in a generic, iterative experimentation-driven model-building process,
      both through informal discussion and using a recently published study as an
      example. Experiments guide the initial development of mathematical models,
      including choice of appropriate template model and parameter revision. The model
      can then be used to generate and test hypotheses quickly and inexpensively,
      aiding in judicious design of future experiments. These experiments, in turn, are
      used to update the model. The model developed at the end of this exercise not
      only predicts functional behavior of the system under study but also provides
      insight into the biophysical underpinnings of signaling networks.

PMID- 22482946
TI  - A framework for modeling the relationship between cellular steady-state and
      stimulus-responsiveness.
AB  - In cell signaling systems, the abundances of signaling molecules are generally
      thought to determine the response to stimulation. However, the kinetics of
      molecular processes, for example receptor trafficking and protein turnover, may
      also play an important role. Few studies have systematically examined this
      relationship between the resting state and stimulus-responsiveness. Fewer still
      have investigated the relative contribution of steady-state concentrations and
      reaction kinetics. Here we describe a mathematical framework for modeling the
      resting state of signaling systems. Among other things, this framework allows
      steady-state concentration measurements to be used in parameterizing kinetic
      models, and enables comprehensive characterization of the relationship between
      the resting state and the cellular response to stimulation.

PMID- 22482944
TI  - Integrated inference and analysis of regulatory networks from multi-level
      measurements.
AB  - Regulatory and signaling networks coordinate the enormously complex interactions
      and processes that control cellular processes (such as metabolism and cell
      division), coordinate response to the environment, and carry out multiple cell
      decisions (such as development and quorum sensing). Regulatory network inference
      is the process of inferring these networks, traditionally from microarray data
      but increasingly incorporating other measurement types such as proteomics, ChIP
      seq, metabolomics, and mass cytometry. We discuss existing techniques for network
      inference. We review in detail our pipeline, which consists of an initial
      biclustering step, designed to estimate co-regulated groups; a network inference
      step, designed to select and parameterize likely regulatory models for the
      control of the co-regulated groups from the biclustering step; and a
      visualization and analysis step, designed to find and communicate key features of
      the network. Learning biological networks from even the most complete data sets
      is challenging; we argue that integrating new data types into the inference
      pipeline produces networks of increased accuracy, validity, and biological
      relevance.

PMID- 22482947
TI  - Stochastic modeling of cellular networks.
AB  - Noise and stochasticity are fundamental to biology because they derive from the
      nature of biochemical reactions. Thermal motions of molecules translate into
      randomness in the sequence and timing of reactions, which leads to cell-cell
      variability ("noise") in mRNA and protein levels even in clonal populations of
      genetically identical cells. This is a quantitative phenotype that has important
      functional repercussions, including persistence in bacterial subpopulations
      challenged with antibiotics, and variability in the response of cancer cells to
      drugs. In this chapter, we present the modeling of such stochastic cellular
      behaviors using the formalism of jump Markov processes, whose probability
      distributions evolve according to the chemical master equation (CME). We also
      discuss the techniques used to solve the CME. These include kinetic Monte Carlo
      simulations techniques such as the stochastic simulation algorithm (SSA) and
      method closure techniques such as the linear noise approximation (LNA).

PMID- 22482945
TI  - Swimming upstream: identifying proteomic signals that drive transcriptional
      changes using the interactome and multiple "-omics" datasets.
AB  - Signaling and transcription are tightly integrated processes that underlie many
      cellular responses to the environment. A network of signaling events, often
      mediated by post-translational modification on proteins, can lead to long-term
      changes in cellular behavior by altering the activity of specific transcriptional
      regulators and consequently the expression level of their downstream targets. As
      many high-throughput, "-omics" methods are now available that can simultaneously
      measure changes in hundreds of proteins and thousands of transcripts, it should
      be possible to systematically reconstruct cellular responses to perturbations in
      order to discover previously unrecognized signaling pathways. This chapter
      describes a computational method for discovering such pathways that aims to
      compensate for the varying levels of noise present in these diverse data sources.
      Based on the concept of constraint optimization on networks, the method seeks to
      achieve two conflicting aims: (1) to link together many of the signaling proteins
      and differentially expressed transcripts identified in the experiments
      "constraints" using previously reported protein-protein and protein-DNA
      interactions, while (2) keeping the resulting network small and ensuring it is
      composed of the highest confidence interactions "optimization". A further
      distinctive feature of this approach is the use of transcriptional data as
      evidence of upstream signaling events that drive changes in gene expression,
      rather than as proxies for downstream changes in the levels of the encoded
      proteins. We recently demonstrated that by applying this method to
      phosphoproteomic and transcriptional data from the pheromone response in yeast,
      we were able to recover functionally coherent pathways and to reveal many
      components of the cellular response that are not readily apparent in the original
      data. Here, we provide a more detailed description of the method, explore the
      robustness of the solution to the noise level of input data and discuss the
      effect of parameter values.

PMID- 22482948
TI  - Quantifying traction stresses in adherent cells.
AB  - Contractile force generation plays a critical role in cell adhesion, migration,
      and extracellular matrix reorganization in both 2D and 3D environments.
      Characterization of cellular forces has led to a greater understanding of cell
      migration, cellular mechanosensing, tissue formation, and disease progression.
      Methods to characterize cellular traction stresses now date back over 30 years,
      and they have matured from qualitative comparisons of cell-mediated substrate
      movements to high-resolution, highly quantitative measures of cellular force.
      Here, we will provide an overview of common methods used to measure forces in
      both 2D and 3D microenvironments. Specific focus will be placed on traction force
      microscopy, which measures the force exerted by cells on 2D planar substrates,
      and the use of confocal reflectance microscopy, which can be used to quantify
      collagen fibril compaction as a metric for 3D traction forces. In addition to
      providing experimental methods to analyze cellular forces, we discuss the
      application of these techniques to a large range of biomedical problems and some
      of the significant challenges that still remain in this field.

PMID- 22482949
TI  - CellOrganizer: Image-derived models of subcellular organization and protein
      distribution.
AB  - This chapter describes approaches for learning models of subcellular organization
      from images. The primary utility of these models is expected to be from
      incorporation into complex simulations of cell behaviors. Most current cell
      simulations do not consider spatial organization of proteins at all, or treat
      each organelle type as a single, idealized compartment. The ability to build
      generative models for all proteins in a proteome and use them for spatially
      accurate simulations is expected to improve the accuracy of models of cell
      behaviors. A second use, of potentially equal importance, is expected to be in
      testing and comparing software for analyzing cell images. The complexity and
      sophistication of algorithms used in cell-image-based screens and assays
      (variously referred to as high-content screening, high-content analysis, or high
      throughput microscopy) is continuously increasing, and generative models can be
      used to produce images for testing these algorithms in which the expected answer
      is known.

PMID- 22482950
TI  - Spatial modeling of cell signaling networks.
AB  - The shape of a cell, the sizes of subcellular compartments, and the spatial
      distribution of molecules within the cytoplasm can all control how molecules
      interact to produce a cellular behavior. This chapter describes how these spatial
      features can be included in mechanistic mathematical models of cell signaling.
      The Virtual Cell computational modeling and simulation software is used to
      illustrate the considerations required to build a spatial model. An explanation
      of how to appropriately choose between physical formulations that implicitly or
      explicitly account for cell geometry and between deterministic versus stochastic
      formulations for molecular dynamics is provided, along with a discussion of their
      respective strengths and weaknesses. As a first step toward constructing a
      spatial model, the geometry needs to be specified and associated with the
      molecules, reactions, and membrane flux processes of the network. Initial
      conditions, diffusion coefficients, velocities, and boundary conditions complete
      the specifications required to define the mathematics of the model. The numerical
      methods used to solve reaction-diffusion problems both deterministically and
      stochastically are then described and some guidance is provided in how to set up
      and run simulations. A study of cAMP signaling in neurons ends the chapter,
      providing an example of the insights that can be gained in interpreting
      experimental results through the application of spatial modeling.

PMID- 22482951
TI  - Stochastic models of cell protrusion arising from spatiotemporal signaling and
      adhesion dynamics.
AB  - During cell migration, local protrusion events are regulated by biochemical and
      physical processes that are in turn coordinated with the dynamic properties of
      cell-substratum adhesion structures. In this chapter, we present a modeling
      approach for integrating the apparent stochasticity and spatial dependence of
      signal transduction pathways that promote protrusion in tandem with adhesion
      dynamics. We describe our modeling framework, as well as its abstraction,
      parameterization, and validation against experimental data. Analytical techniques
      for identifying and evaluating the effects of model bistability on simulation
      simulation results are shown, and implications of this analysis for understanding
      cell protrusion behavior are offered.

PMID- 22482952
TI  - Nonparametric variable selection and modeling for spatial and temporal regulatory
      networks.
AB  - Because of the increasing diversity of data sets and measurement techniques in
      biology, a growing spectrum of modeling methods is being developed. It is
      generally recognized that it is critical to pick the appropriate method to
      exploit the amount and type of biological data available for a given system.
      Here, we describe a method for use in situations where temporal data from a
      network is collected over multiple time points, and in which little prior
      information is available about the interactions, mathematical structure, and
      statistical distribution of the network. Our method results in models that we
      term Nonparametric exterior derivative estimation Ordinary Differential Equation
      (NODE) model's. We illustrate the method's utility using spatiotemporal gene
      expression data from Drosophila melanogaster embryos. We demonstrate that the
      NODE model's use of the temporal characteristics of the network leads to
      quantifiable improvements in its predictive ability over nontemporal models that
      only rely on the spatial characteristics of the data. The NODE model provides
      exploratory visualizations of network behavior and structure, which can identify
      features that suggest additional experiments. A new extension is also presented
      that uses the NODE model to generate a comb diagram, a figure that presents a
      list of possible network structures ranked by plausibility. By being able to
      quantify a continuum of interaction likelihoods, this helps to direct future
      experiments.

PMID- 22482953
TI  - Quantitative models of the mechanisms that control genome-wide patterns of animal
      transcription factor binding.
AB  - Animal transcription factors drive complex spatial and temporal patterns of gene
      expression during development by binding to a wide array of genomic regions.
      While the in vivo DNA binding landscape and in vitro DNA binding affinities of
      many such proteins have been characterized, our understanding of the forces that
      determine where, when, and the extent to which these transcription factors bind
      DNA in cells remains primitive. In this chapter, we describe computational
      thermodynamic models that predict the genome-wide DNA binding landscape of
      transcription factors in vivo and evaluate the contribution of biophysical
      determinants, such as protein-protein interactions and chromatin accessibility,
      on DNA occupancy. We show that predictions based only on DNA sequence and in
      vitro DNA affinity data achieve a mild correlation (r=0.4) with experimental
      measurements of in vivo DNA binding. However, by incorporating direct
      measurements of DNA accessibility in chromatin, it is possible to obtain much
      higher accuracy (r=0.6-0.9) for various transcription factors across known target
      genes. Thus, a combination of experimental DNA accessibility data and
      computational modeling of transcription factor DNA binding may be sufficient to
      predict the binding landscape of any animal transcription factor with reasonable
      accuracy.

PMID- 22482954
TI  - Computational analysis of live cell images of the Arabidopsis thaliana plant.
AB  - Quantitative studies in plant developmental biology require monitoring and
      measuring the changes in cells and tissues as growth gives rise to intricate
      patterns. The success of these studies has been amplified by the combined
      strengths of two complementary techniques, namely live imaging and computational
      image analysis. Live imaging records time-lapse images showing the spatial
      temporal progress of tissue growth with cells dividing and changing shape under
      controlled laboratory experiments. Image processing and analysis make sense of
      these data by providing computational ways to extract and interpret quantitative
      developmental information present in the acquired images. Manual labeling and
      qualitative interpretation of images are limited as they don't scale well to
      large data sets and cannot provide field measurements to feed into mathematical
      and computational models of growth and patterning. Computational analysis, when
      it can be made sufficiently accurate, is more efficient, complete, repeatable,
      and less biased. In this chapter, we present some guidelines for the acquisition
      and processing of images of sepals and the shoot apical meristem of Arabidopsis
      thaliana to serve as a basis for modeling. We discuss fluorescent markers and
      imaging using confocal laser scanning microscopy as well as present protocols for
      doing time-lapse live imaging and static imaging of living tissue. Image
      segmentation and tracking are discussed. Algorithms are presented and
      demonstrated together with low-level image processing methods that have proven to
      be essential in the detection of cell contours. We illustrate the application of
      these procedures in investigations aiming to unravel the mechanical and
      biochemical signaling mechanisms responsible for the coordinated growth and
      patterning in plants.

PMID- 22482955
TI  - Multi-scale modeling of tissues using CompuCell3D.
AB  - The study of how cells interact to produce tissue development, homeostasis, or
      diseases was, until recently, almost purely experimental. Now, multi-cell
      computer simulation methods, ranging from relatively simple cellular automata to
      complex immersed-boundary and finite-element mechanistic models, allow in silico
      study of multi-cell phenomena at the tissue scale based on biologically observed
      cell behaviors and interactions such as movement, adhesion, growth, death,
      mitosis, secretion of chemicals, chemotaxis, etc. This tutorial introduces the
      lattice-based Glazier-Graner-Hogeweg (GGH) Monte Carlo multi-cell modeling and
      the open-source GGH-based CompuCell3D simulation environment that allows rapid
      and intuitive modeling and simulation of cellular and multi-cellular behaviors in
      the context of tissue formation and subsequent dynamics. We also present a
      walkthrough of four biological models and their associated simulations that
      demonstrate the capabilities of the GGH and CompuCell3D.

PMID- 22482956
TI  - Multiscale model of fibrin accumulation on the blood clot surface and platelet
      dynamics.
AB  - A multiscale computational model of thrombus (blood clot) development is extended
      by incorporating a submodel describing formation of fibrin network through
      "fibrin elements" representing regions occupied by polymerized fibrin.
      Simulations demonstrate that fibrin accumulates on the surface of the thrombus
      and that fibrin network limits growth by reducing thrombin concentrations on the
      thrombus surface and decreasing adhesivity of resting platelets in blood near
      thrombus surface. These results suggest that fibrin accumulation may not only
      increase the structural integrity of the thrombus but also considerably
      contribute toward limiting its growth. Also, a fast Graphics Processing Unit
      implementation is described for a multiscale computational model of the platelet
      blood flow interaction.

PMID- 22482957
TI  - [Evaluation of contractility and postloading in the intensive care unit].
AB  - Cardiovascular failure is a common disorder in critical care medicine. When
      admitted to the ICU, patients with hemodynamic deterioration should be examined
      rapidly to correctly assess the main determinants of cardiovascular function
      (preload, afterload and contractility). This review examines the assessment of
      contractility and afterload involving the combined use of several hemodynamic
      monitors, which allows different approaches to the same problem, with a view to
      improving the efficiency of management and treatment in critically ill patients.

PMID- 22482959
TI  - Tuberculosis peritonitis.

PMID- 22482958
TI  - Polymer nanoparticle-mediated delivery of microRNA inhibition and alternative
      splicing.
AB  - The crux of current RNA-based therapeutics relies on association of synthetic
      nucleic acids with cellular RNA targets. Antisense oligonucleotide binding to
      mature microRNA and splicing junctions on pre-mRNA represent methods of gene
      therapy that respectively inhibit microRNA-mediated gene regulation and induce
      alternative splicing. We have developed biodegradable polymer nanoparticles,
      which are coated with cell-penetrating peptides, that can effectively deliver
      chemically modified oligonucleotide analogues to achieve these forms of gene
      regulation. We found that this nanoparticle system could block the activity of
      the oncogenic microRNA, miR-155, as well as modulate splicing to attenuate the
      expression of the proto-oncogene, Mcl-1. Regulation of these genes in human
      cancer cells reduced cell viability and produced pro-apoptotic effects. These
      findings establish polymer nanoparticles as delivery vectors for nonconventional
      forms of gene therapy activated by cellular delivery of RNA-targeted molecules,
      which have strong therapeutic implications.

PMID- 22482960
TI  - Prediction of hemorrhage in placenta previa.
AB  - Placenta previa poses a high risk for massive hemorrhage, from the antenatal
      period until after Cesarean section. This condition increases the risk of
      maternal and neonatal mortality and morbidity. In cases of placenta previa, the
      prenatal prediction of sudden bleeding during pregnancy and blood loss during
      Cesarean section, and the assessment of risk for adherence of the placenta using
      an ultrasound examination, can improve the perinatal outcome. Therefore,
      ultrasonographic findings associated with the prediction of massive bleeding in
      cases of placenta previa are reviewed in this article.

PMID- 22482961
TI  - Review of myomectomy.
AB  - Uterine fibroids (also called leiomyomas or myomas) are the most common disorder
      among women of reproductive age, with an incidence of between 20% and 80%; they
      are often detected incidentally in routine healthy examinations, through bimanual
      pelvic and/or ultrasound examination, because uterine fibroids are rarely
      associated with symptoms. Sometimes, uterine fibroids may be complicated by a
      variety of symptoms, including menstrual disturbance (e.g., menorrhagia,
      dysmenorrhea, intermenstrual bleeding), pressure symptoms, bloated sensation,
      increased urinary frequency, bowel disturbance, or pelvic pain; therefore
      definite treatment is requested. Hysterectomy may be the first choice for women
      who have completed their child-birth; however, many women may prefer to keep the
      uterus if the uterine fibroids-related symptoms can be appropriately controlled.
      Among these conservative therapies, myomectomy may be one of the most popular
      methods for the woman who would like to preserve her future fertility, as the
      majority of symptoms can be relieved by myomectomy; this contributes to the value
      of this review. This review addresses the use of myomectomy in the management of
      symptomatic uterine fibroids.

PMID- 22482962
TI  - Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence
      and multiple pterygium syndrome associated with neuromuscular junction disorders:
      a review.
AB  - Fetal akinesia deformation sequence is a clinically and genetically heterogeneous
      disorder characterized by a variable combination of arthrogryposis, fetal
      akinesia, intrauterine growth restriction, developmental abnormalities such as
      cystic hygroma, pulmonary hypoplasia, cleft palate, cryptorchidism, cardiac
      defects and intestinal malrotation, and occasional pterygia of the limbs.
      Multiple pterygium syndrome is a clinically and genetically heterogeneous
      disorder characterized by pterygia of the neck, elbows and/or knees,
      arthrogryposis, and other phenotypic features such as short stature, genital
      abnormalities, craniofacial abnormalities, clubfoot, kyphoscoliosis, and cardiac
      abnormalities. Fetal akinesia deformation sequence may phenotypically overlap
      with the lethal type of multiple pterygium syndrome. This article provides a
      comprehensive review of prenatal diagnosis and genetic analysis of fetal akinesia
      deformation sequence and multiple pterygium syndrome associated with
      neuromuscular junction disorders. Prenatal diagnosis of fetal akinesia along with
      cystic hygroma, increased nuchal translucency, nuchal edema, hydrops fetalis,
      arthrogryposis, pterygia, and other structural abnormalities should include a
      differential diagnosis of neuromuscular junction disorders. Genetic analysis of
      mutations in the neuromuscular junction genes such as CHRNA1, CHRND, CHRNG,
      CNTN1, DOK7, RAPSN, and SYNE1 may unveil the pathogenetic cause of fetal akinesia
      deformation sequence and multiple pterygium syndrome, and the information
      acquired is helpful for genetic counseling and clinical management.

PMID- 22482963
TI  - Robotic surgery in complicated gynecologic diseases: experience of Tri-Service
      General Hospital in Taiwan.
AB  - OBJECTIVE: Minimally invasive surgery has been the trend in various specialties
      and continues to evolve as new technology develops. The development of robotic
      surgery in gynecology remains in its infancy. The present study reports the first
      descriptive series of robotic surgery in complicated gynecologic diseases in
      Taiwan. MATERIALS AND METHODS: From March 2009 to February 2011, the records of
      patients undergoing robotic surgery using the da Vinci Surgical System were
      reviewed for patient demographics, indications, operative time, hospital stay,
      conversion to laparotomy, and complications. RESULTS: Sixty cases were reviewed
      in the present study. Forty-nine patients had benign gynecologic diseases, and 11
      patients had malignancies. These robot-assisted laparoscopic procedures include
      nine hysterectomy, 15 subtotal hysterectomy, 13 myomectomy, eight staging
      operation, two radical hysterectomy, five ovarian cystectomy, one bilateral
      salpingo-oophorectomy and myomectomy, two resections of deep pelvic
      endometriosis, one pelvic adhesiolysis, three sacrocolpopexy and one tuboplasty.
      Thirty-three patients had prior pelvic surgery, and one had a history of pelvic
      radiotherapy. Adhesiolysis was necessary in 38 patients to complete the whole
      operation. Robotic myomectomy was easily accomplished in patients with huge
      uterus or multiple myomas. The suturing of myometrium or cervical stump after
      ligation of the uterine arteries minimized the blood loss. In addition, it was
      much easier to dissect severe pelvic adhesions. The dissection of para-aortic
      lymph nodes can be easily accomplished. All these surgeries were performed
      smoothly without ureteral, bladder or bowel injury. CONCLUSION: The present
      analyses include various complicated gynecologic conditions, which make the
      estimation of the effectiveness of robotic surgery in each situation individually
      not appropriate. However, our experiences do show that robotic surgery is
      feasible and safe for patients with complicated gynecologic diseases.

PMID- 22482964
TI  - Characteristics of early-onset neonatal sepsis caused by Escherichia coli.
AB  - OBJECTIVE: This study was conducted to document the perinatal risk factors
      associated with early-onset neonatal Escherichia coli sepsis and adverse neonatal
      outcomes. MATERIALS AND METHODS: A case-control study of early-onset E coli
      sepsis compared with that of non-E coli sepsis was conducted by a retrospective
      data review of all infants with a diagnosis of sepsis during the first 7 days of
      life from the pediatric unit of Mackay Memorial Hospital from January 2004 to
      October 2008. After adjustment for gestational age, each patient with E coli
      early-onset sepsis was further compared with two gestational age-matched
      uninfected controls. RESULTS: Compared with infants with non-E coli sepsis (n =
      27), infants with E coli sepsis (n = 19) were more likely to have preterm birth,
      especially at less than 30 weeks of gestation (47% vs. 4%, p < 0.01), very low
      birth weights (<1500 g; 47% vs. 4%, p < 0.01), intrapartum fever (26% vs. 4%, p =
      0.036), preterm premature rupture of membranes (PPROM; 74% vs. 11%, p < 0.01),
      prolonged rupture of membranes (>24 hours; 47% vs. 0%, p < 0.01), antibiotic use
      (63% vs. 15%, p < 0.01), and sepsis onset on the first day of life (63% vs. 15%,
      p < 0.01). After adjusting for gestational age, intrapartum fever (26% vs. 5%, p
      = 0.035) and PPROM (74% vs. 39%, p = 0.015) were more common in infants with E
      coli sepsis. Fifteen of the 19 E coli isolates (79%) were ampicillin-resistant,
      and three (16%) were gentamicin-resistant. Antepartum and intrapartum antibiotic
      exposure was associated with ampicillin-resistant E coli sepsis (100% vs. 43%, p
      < 0.01). CONCLUSION: Early-onset E coli sepsis is more common in premature and
      very low birth weight infants and is more likely associated with intrapartum
      fever, PPROM, and sepsis onset on the first day of life than non-E coli sepsis.
      Broad-spectrum, multiple antibiotics or longer duration of antibiotic exposure
      may be associated with antibiotic-resistant pathogen infection.

PMID- 22482965
TI  - Clinical characteristics and assisted reproductive technology outcomes in
      infertile foreign brides: comparison with native brides in south Taiwan.
AB  - OBJECTIVE: This study was conducted to determine if differences in clinical
      characteristics, embryonic development, and pregnancy outcomes exist between
      infertile foreign and native brides undergoing assisted reproductive technology
      (ART) treatment in a foreign-bride-immigrating country of Taiwan. MATERIAL AND
      METHODS: A retrospective, case-control design was use to recruit consecutive
      infertile women seeking ART treatment for study. The treatment protocol consisted
      of controlled ovarian hyperstimulation with down-regulation and gonadotropin and
      ART method with conventional in vitro fertilization or intracytoplasmic sperm
      injection. Among the 1083 ART treatment cycles, 97 (9%) were from foreign brides
      and 986 (91%) from native brides. Records of those who received transfer of fresh
      embryos obtained by using husband sperm for fertilization were collected for
      analysis. A case-control design with adjustment of bride age was used to select
      the records of 86 infertile foreign and 172 native brides for the study.
      Infertility cause, bride age, retrieved oocyte number and maturity, fertilization
      rate, embryo score, and post-embryo transfer results were assessed. RESULTS: The
      foreign bride couples had significantly greater infertility due to tubal (36%)
      and combination (8.1%) factors than native bride couples (20.3% and 4.1%,
      respectively). Days of gonadotropin stimulation, number of oocytes retrieved,
      fertilization rate, embryo score, implantation rate, or clinical pregnancy rate,
      and live birth rate did not differ between the two groups. CONCLUSION: The cause
      of infertile foreign bride couples requiring ART treatment had a higher
      percentage of tubal and combination factors, but similar ART outcomes.

PMID- 22482966
TI  - Reprogramming human endometrial fibroblast into induced pluripotent stem cells.
AB  - OBJECTIVE: A recent breakthrough demonstrated that ectopic expression of four
      genes is sufficient to reprogram human fibroblasts into inducible pluripotent
      stem cells (iPSCs). However, it remains unknown whether human endometrial
      fibroblasts (EMFs) are capable of being reprogrammed into EMF-derived iPSCs (EMF
      iPSCs). METHODS: EMFs were obtained from donors in their third and fourth decade
      of life and were reprogrammed into iPSCs using retroviral transduction with Oct
      4, Sox2, Klf4, and c-Myc. RESULTS: The EMF-iPSCs displayed the accelerated
      expression of endogenous Nanog and OCT-4 during reprogramming compared with EMFs.
      As a result, EMF-iPSC colonies that could be subcultured and propagated were
      established as early as 12 days after transduction. After 2 weeks of
      reprogramming, the human endometrial cells yielded significantly higher numbers
      of iPSC colonies and formed more 3D spheroid bodies than the EMFs. We have shown
      that human EMF-iPSCs are able to differentiate into neuronal-like cells,
      adipocytes, and osteocyte-like cells that express specific osteogenic genes.
      CONCLUSION: Human EMFs can undergo reprogramming to establish pluripotent stem
      cell lines in female donors by the retroviral transduction of Oct-4, Sox2, Klf4,
      and c-Myc.

PMID- 22482967
TI  - New primers for methylation-specific polymerase chain reaction enhance
      specificity of detecting STAT1 methylation.
AB  - OBJECTIVE: Signal transducer and activator of transcription (STAT)1 is a key
      tumor suppressor, which is always methylated in a variety of human cancers.
      However, nonspecific primers for the detection of specific promoter
      hypermethylation of STAT1 gene can lead to false-positive or false-negative
      results for gene methylation. MATERIALS AND METHODS: We designed new primers for
      the detection of STAT1 methylation and compared the sensitivities and
      specificities of these new primers with prior published primers by methylation
      specific polymerase chain reaction (PCR) from ovarian clear cell carcinomas. The
      mRNA expression levels of STAT1 in these cancerous tissues were also evaluated by
      reverse-transcriptase PCR and correlated with the results of promoter methylation
      of STAT1 gene. RESULTS: Nine (39%) of the 23 samples detected by the new primers
      and 13 samples (56%) detected by prior published primers showed STAT1
      methylation. A direct DNA sequencing test revealed that four of the 13 samples
      (30.8%) showed false positivity for STAT1 methylation using the prior published
      primers. In contrast, none of the nine samples was false-positive for the
      detection of STAT1 methylation using the new primers. The new primers for the
      detection of STAT1 methylation showed 100% specificity and 100% sensitivity
      without false positivity. CONCLUSION: Specific primers for methylation-specific
      PCR are mandatory for the accurate detection of STAT1 gene methylation. Besides,
      specific primers can generate correct interpretation of STAT1 gene methylation,
      and its correlation with the clinicopathological characteristics and outcome of
      cancer patients.

PMID- 22482968
TI  - Estrogen receptor expression affected by hypoxia inducible factor-1alpha in
      stromal cells from patients with endometriosis.
AB  - OBJECTIVE: Endometriosis is an estrogen-dependent disease. The aim of this study
      was to evaluate the different expression of estrogen receptors (ER) and its
      relation to hypoxia inducible factor-1alpha (HIF-1alpha) in stromal cells from
      women with endometriosis. MATERIALS AND METHODS: Paired eutopic endometrial and
      ectopic endometriotic stromal cells were isolated from women with endometriosis
      while they underwent laparoscopy. The expression of ERalpha and ERbeta was
      measured by reverse transcription-polymerase chain reaction and Western blot.
      Regulation of ER expression was evaluated by HIF-1alpha knockdown via short
      interference RNA. RESULTS: The expression of ERbeta was significantly increased
      in ectopic stromal cells. Treatment of endometrial stromal cells with hypoxia
      induced ERbeta expression. Knockdown of HIF-1alpha abolished hypoxia-induced
      ERbeta expression and increased ERalpha expression. CONCLUSION: The expression of
      ERbeta is regulated by hypoxia. Results of this study will provide important
      information in the involvement of hypoxia factors in mediating estrogen action
      via different ER expression in endometriosis.

PMID- 22482969
TI  - A prospective study of nerve-sparing radical hysterectomy for uterine cervical
      carcinoma in Taiwan.
AB  - OBJECTIVE: Surgical therapy for cervical carcinoma carries a significant risk of
      functional impairment to the bladder. This study evaluates the feasibility and
      complications of nerve-sparing radical hysterectomy (NRH) in Taiwan. METHODS:
      Between March 2010 and March 2011, consecutive patients diagnosed with early
      stage cervical cancer (FIGO stage Ia2 to Ib1) and tumor size < 3 cm were
      recruited prospectively to undergo NRH or conventional radical hysterectomy (RH).
      Patients with histories of urinary stress incontinence or bladder dysfunction
      disease were excluded. A modified Tokyo nerve-sparing radical hysterectomy was
      performed. RESULTS: A total of 30 patients were enrolled. Among these, 18
      patients underwent NRH with successful bilaterally nerve-sparing procedures in 15
      cases (83%), unilaterally nerve-sparing procedures in 2 cases (11%), and a
      failure in 1 case (6%). The indwelling catheter was removed on postoperative day
      6. The mean+/-SD duration from operation to spontaneous voiding was 6.8 +/- 1.5
      days for women who underwent NRH; the corresponding duration for women who
      underwent RH or failed NRH was 20.6 +/- 3 days. None of the patients who
      underwent NRH required intermittent catheterization. All 12 patients who
      underwent RH needed self-catheterization after discharge. There was a significant
      reduction in the incidence of postoperative self-catheterization (p<0.01) and
      bladder dysfunction (p<0.006). Average satisfaction score analyzed by the Likert
      scale questionnaire was 4.5 for the NRH group and 1.9 for RH group (p<0.0001).
      CONCLUSIONS: We concluded that the new technique of NRH can reduce postoperative
      bladder dysfunctions.

PMID- 22482970
TI  - Pregnancy outcomes according to increasing maternal age.
AB  - OBJECTIVES: To investigate the risks of increasing maternal age on the perinatal
      and obstetric outcomes. MATERIALS AND METHODS: Information about 29,760 singleton
      pregnancies delivered between 2005 and 2008 was extracted from our database.
      Patients were categorized into four groups according to age: 20-29 years, 30-34
      years, 35-39 years, and >=40 years. Multivariable logistic regression analysis
      was used to evaluate the adjusted odd ratios (AORs) of adverse pregnancy outcomes
      according to maternal age after adjusting for parity, body mass index, medical
      history and use of in vitro fertilization. RESULTS: The majority of adverse
      perinatal outcomes were associated with a maternal age >=35 years as follows: low
      birth weight (AOR 1.2 and 1.6 for women aged 35-39 years and >=40 years,
      respectively); Apgar score < 7 at 1 minute (AOR: 1.7 and 1.8); and chromosomal
      anomaly (AOR: 2.7 and 12.3). However, women aged >=30 years also had greater
      risks for adverse maternal outcomes such as: gestational diabetes (AOR: 2.0, 3.6
      and 5.1 for women aged 30-34 years, 35-39 years and >=40 years, respectively);
      placenta previa (AOR: 1.6, 2.1 and 3.6); and cesarean delivery (AOR: 1.5, 2.3,
      and 4.1), as well as adverse fetal outcomes such as: preterm delivery (AOR: 1.2,
      1.4 and 1.8) and neonatal intensive care unit transfer (AOR: 1.1, 1.2, and 1.6).
      CONCLUSION: Increasing maternal age is an independent and substantial risk factor
      for adverse perinatal and obstetric outcomes. These adverse outcomes become more
      common as increasing maternal age without a clear cutoff age.

PMID- 22482971
TI  - Simultaneous laparoscopy for endometriotic women undergoing in vitro
      fertilization.
AB  - OBJECTIVE: The aim of this study was to investigate simultaneous laparoscopy in
      endometriotic women with infertility undergoing in vitro fertilization (IVF).
      MATERIALS AND METHODS: Forty-seven infertile patients with endometriosis were
      enrolled in this retrospective study and underwent IVF cycles in a university
      affiliated hospital. RESULTS: The chemical pregnancy, clinical pregnancy and live
      birth rates were statistically significantly different between patients with
      minimal or mild stage endometriosis and patients with moderate or severe stage
      endometriosis, who received simultaneous laparoscopy and modified IVF with a GnRH
      antagonist protocol. A higher live birth rate was achieved in IVF patients with
      minimal or mild stage endometriosis combined with laparoscopic treatment, than in
      patients who received traditional IVF with prior laparoscopic surgery for
      endometrioma. CONCLUSION: Simultaneous laparoscopy combined with a modified IVF
      (GnRH antagonist) protocol may benefit patients with minimal and mild
      endometriosis. Traditional GnRH agonist IVF cycles may improve the fecundity
      rates in women with moderate and severe endometriosis after laparoscopic
      treatment.

PMID- 22482972
TI  - Mosaic ring chromosome 21, monosomy 21, and isodicentric ring chromosome 21:
      prenatal diagnosis, molecular cytogenetic characterization, and association with
      2-Mb deletion of 21q21.1-q21.2 and 5-Mb deletion of 21q22.3.
AB  - OBJECTIVE: To present the perinatal findings and molecular cytogenetic
      characterization of prenatally detected mosaic r(21). MATERIALS, METHODS, AND
      RESULTS: A 29-year-old primigravid woman underwent amniocentesis at 22 weeks'
      gestation because of hyperechogenic cardiac foci and intrauterine growth
      restriction. Amniocentesis revealed a karyotype of 46,XY,r(21)[15]/45,XY,-21[5].
      The parental karyotypes were normal. The woman requested repeat amniocentesis.
      Oligonucleotide-based array comparative genomic hybridization was applied to the
      uncultured amniocytes, rapidly detecting a 2.09-Mb deletion of 21q21.1-q21.2
      (21,495,262-23,580,815 bp) and a 5.03-Mb deletion of 21q22.3-q22.3 (41,887,412
      46,914,715 bp). Cytogenetic analysis revealed a karyotype of
      46,XY,r(21)[8]/45,XY,-21[3]/46,XY,idic r(21)[1]. The pregnancy was terminated,
      and a malformed fetus was delivered with clinodactyly, short big toes, separation
      between the first and second toes, prominent nasal bridge, downward slanting
      palpebral fissures, protuberant occiput, prominent forehead, broad anteverted
      nasal tip, long philtrum, thin upper lip, small mouth, and micrognathia. The
      placenta had a karyotype of 46,XY,r(21)[83]/45,XY,-21[11]/46,XY,idic r(21)[6],
      and the cord blood lymphocytes had a karyotype of 46,XY,r(21)[88]/45,XY,
      21[9]/46,XY,idic r(21)[3]. Polymorphic DNA marker analysis determined a maternal
      origin for the deletion. CONCLUSION: An extra interstitial 21q deletion can be
      associated with mosaic r(21) in addition to a terminal 21q deletion. aCGH is
      useful in determining the breakpoints and associated subtle structural
      abnormalities in cases of prenatally detected ring chromosome in order to
      facilitate genetic counseling.

PMID- 22482973
TI  - Trisomy 7 mosaicism at amniocentesis: interphase FISH, QF-PCR, and aCGH analyses
      on uncultured amniocytes for rapid distinguishing of true mosaicism from
      pseudomosaicism.
AB  - OBJECTIVE: To present prenatal diagnosis of true trisomy 7 mosaicism. MATERIALS,
      METHODS AND RESULTS: A 36-year-old woman underwent amniocentesis at 18 weeks of
      gestation. Amniocentesis revealed a karyotype of 47,XY,+7[20]/46,XY[9]. The
      parental karyotypes were normal. Repeated amniocentesis was performed at 20 weeks
      of gestation. Array comparative genomic hybridization (aCGH) analysis on
      uncultured amniocytes manifested a genomic gain in chromosome 7. Quantitative
      fluorescent polymerase chain reaction (QF-PCR) analysis on uncultured amniocytes
      showed a biparental diallelic pattern with a dosage increase in the maternal
      allele. Interphase fluorescence in situ hybridization (FISH) on uncultured
      amniocytes revealed three 7q-specific signals in 13 of 50 (26%) of the cells. The
      cultured amniocytes had a karyotype of 47,XY,+7[12]/46,XY[14]. The ultrasound
      findings were unremarkable. The pregnancy was subsequently terminated, and a
      fetus was delivered with facial dysmorphisms. Postnatal tissue samplings revealed
      the mosaic trisomy 7 level of 37.5% (15/40), 30% (12/40), 42.5% (17/40), 82.5%
      (33/40), 52.5% (21/40), and 27.5% (11/40) in skin, liver, lungs, placenta,
      membrane, and cord, respectively. The cord blood had a karyotype of 46,XY.
      PEG1/MEST methylation-sensitive high-resolution melting PCR assay of cord blood
      showed no uniparental disomy for chromosome 7. CONCLUSION: Interphase FISH, QF
      PCR, and aCGH analyses on uncultured amniocytes are useful for rapid
      distinguishing of true mosaicism from pseudomosaicism for trisomy 7 at
      amniocentesis. Cord blood sampling for confirmation of fetal trisomy 7 mosaicism
      is not practical.

PMID- 22482974
TI  - Severe 2009 H1N1 infection in early pregnancy.
AB  - OBJECTIVE: Because pregnancy suppresses the immune system, women at any stage of
      pregnancy are more susceptible to bacterial and viral infection. Pregnant women
      might thus be at increased risk of complications from pandemic H1N1 virus
      infection, and illness may progress rapidly. CASE REPORT: A 23-year-old
      primigravida at 9 weeks' gestation was presented to our institution because of
      the sudden onset of sore throat, fever, chills, and vomiting for 5 days. She was
      diagnosed with early pregnancy H1N1 infection, vulvar herpes infection, and
      impending intravascular disseminated coagulopathy. Oseltamivir (Tamiflu) 75 mg
      and valacyclovir 500 mg were then administered orally twice daily for 5 days. The
      patient's fever, chills, and vomiting subsided 2 days later. The real-time
      reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of nasal
      discharge for influenza virus types A and B showed positive results for the
      A/H1N1 influenza virus. The early pregnancy was terminated by therapeutic
      curettage at the patient's request. The surgical specimen revealed products of
      conception with the presence of necrotic chorionic villi, and focal lymphocytes
      in decidual tissue. RT-PCR analysis of gestational tissue for A/H1N1 was
      negative. CONCLUSION: Pregnant women with H1N1 infection seem to benefit from
      antiviral therapy.

PMID- 22482975
TI  - Mature cystic teratoma of the uterosacral ligament successfully treated with
      laparoendoscopic single-site surgery.
AB  - OBJECTIVE: Although the majority of teratomas are encountered in the ovary,
      extragonadal mature cystic teratoma is an unusual disease entity, and the most
      common site is the omentum. CASE REPORT: The occurrence of this tumor on a
      uterosacral ligament is extremely rare with enigmatic etiology. To our knowledge,
      there have been only three cases reported to date that describe a mature cystic
      teratoma of the uterosacral ligament, and this is the first report of successful
      treatment of these rare tumors with laparoendoscopic single-site surgery (LESS).
      CONCLUSION: In the present study, we report a mature cystic teratoma of the
      uterosacral ligament successfully treated with LESS in a 34-year-old woman with a
      preoperative diagnosis of mature cystic teratoma of the left ovary.

PMID- 22482976
TI  - Uterine carcinosarcoma associated with pelvic radiotherapy for sacral chordoma: a
      case report.
AB  - OBJECTIVE: Postirradiation sarcoma of the female genital tract is rare, but a
      recognized event. Most reported cases have been associated with history of
      radiotherapy for various gynecologic conditions, particularly cancer of the
      uterine cervix and abnormal uterine bleeding. The occurrence of uterine sarcoma
      secondary to radiotherapy for a non-gynecologic tumor and, furthermore, this
      condition being simultaneous with the recurrence of primary tumor is unique. CASE
      REPORT: A 67-year-old woman presented with a uterine mass which was diagnosed as
      a sarcoma by endometrial curettage and history of pelvic radiotherapy 23 years
      previously for sacral chordoma. Surgical staging procedure for uterine malignancy
      was performed. The final pathologic diagnosis was carcinosarcoma of the uterus.
      CONCLUSION: In uterine masses seen in patients with history of irradiation to the
      pelvic field, the probability of uterine sarcomas should always be kept in mind.
      These tumors may occur simultaneously with recurrence of primary tumor previously
      treated by adjuvant radiation therapy.

PMID- 22482977
TI  - Rapid aneuploidy diagnosis of partial trisomy 7q (7q34->qter) and partial
      monosomy 10q (10q26.12->qter) by array comparative genomic hybridization using
      uncultured amniocytes.
AB  - OBJECTIVE: To present rapid aneuploidy diagnosis (RAD) of partial trisomy 7q
      (7q34->qter) and partial monosomy 10q (10q26.12->qter) by array comparative
      genomic hybridization (aCGH) using uncultured amniocytes. CASE REPORT: A 34-year
      old, gravida 2, para 1, woman underwent amniocentesis at 20 weeks of gestation
      because of a previous mentally retarded child with an unbalanced reciprocal
      translocation inherited from the carrier father who had a karyotype of
      46,XY,t(7;10) (q34;q26.12). Her first child was initially found to have a normal
      karyotype by routine cytogenetic analysis, but a cryptic chromosomal abnormality
      was subsequently diagnosed by aCGH. During this pregnancy, RAD by oligonucleotide
      based aCGH using uncultured amniocytes revealed a 16.4-Mb duplication of 7q34
      q36.3 and a 12.7-Mb deletion of 10q26.12-q26.3. Conventional cytogenetic analysis
      using cultured amniocytes revealed a karyotype of
      46,XX,der(10)t(7;10)(q34;q26.12)pat. The parents elected to terminate the
      pregnancy. A malformed female fetus was delivered with a high prominent forehead,
      hypertelorism, epicanthic folds, a broad depressed nasal bridge, a prominent nose
      with anteverted nostrils, micrognathia, a short neck, large low-set ears,
      clinodactyly, small big toes, and normal female external genitalia. CONCLUSION:
      aCGH is a useful tool for RAD of subtle chromosomal rearrangements in pregnancy,
      especially under the circumstance of a previous abnormal child with an unbalanced
      translocation derived from a parental subtle reciprocal translocation.

PMID- 22482978
TI  - Short rib-polydactyly syndrome type II (Majewski): prenatal diagnosis, perinatal
      imaging findings and molecular analysis of the NEK1 gene.
AB  - OBJECTIVE: To demonstrate perinatal imaging findings and to investigate the
      mutation in the NEK1 gene in a fetus with type II short rib-polydactyly syndrome
      (SRPS) (Majewski). CASE REPORT: A 34-year-old woman with a past history of fetal
      SRPS was referred to the hospital at 16 weeks of gestation because of sonographic
      diagnosis of short limbs in the fetus. Fetal ultrasound revealed short ribs,
      short limbs, absence of tibiae, polydactyly, syndactyly and choroid plexus cysts.
      At 21 weeks of gestation, polycystic kidneys were found. The pregnancy was
      terminated, and a fetus was delivered with facial dysmorphism, a median cleft
      lip, a narrow chest, micromelia, aplasia of tibiae, hypoplastic nails, syndactyly
      and postaxial polydactyly. The karyotype was 46,XX. Molecular analysis of fetal
      tissues showed a paternal-origin heterozygous splice site mutation in intron 7
      (c.465-1 G>A) in the NEK1 gene, but no mutations in the genes of WDR35, DYNC2H1,
      IFT80, EVC and EVC2. The NEK1 mutation causes an alteration of the splice
      acceptor site of intron 7 (IVS7-1 G>A). No second mutation was identified.
      CONCLUSION: Tibial aplasia, choroid plexus cysts and polycystic kidneys can be
      prominent prenatal ultrasound findings of type II SRPS. The present case provides
      evidence for a correlation of NEK1 mutation with type II SRPS.

PMID- 22482979
TI  - Ultrasound-guided hydrosalpinx aspiration during oocyte retrieval and a mouse
      embryo assay of hydrosalpinx fluid in a woman with hydrosalpinx and hydrometra
      during in vitro fertilization treatment.

PMID- 22482980
TI  - Prenatal diagnosis of mosaic ring chromosome 15 with abnormal maternal serum Down
      syndrome screening and Dandy-Walker malformation.

PMID- 22482981
TI  - Successful management of a giant primary epidermoid cyst arising in the labia
      majora.

PMID- 22482982
TI  - Parasitic peritoneal leiomyomatosis mimicking intra-abdominal abscess with
      hematoma.

PMID- 22482983
TI  - Dramatic changes of CA 125 levels in a pregnant woman with a degenerated
      subserosal myoma.

PMID- 22482984
TI  - Adenoid cystic carcinoma of Bartholin's gland.

PMID- 22482985
TI  - Using a half dose of leuplin depot in a long-term protocol for in vitro
      fertilization.

PMID- 22482986
TI  - Rapid aneuploidy diagnosis by multiplex ligation-dependent probe amplification
      using uncultured amniocytes in pregnancy with major fetal structural
      abnormalities.

PMID- 22482987
TI  - Prenatal diagnosis of partial trisomy 16p (16p12.2->pter) and partial monosomy
      22q (22q13.31->qter) associated with increased nuchal translucency and abnormal
      maternal serum biochemistry in the first trimester.

PMID- 22482988
TI  - Unexplained shortening of the long bones in the third trimester as the only
      prenatal feature in a male fetus with 45,X/46,X,r(Y) mosaicism.

PMID- 22482989
TI  - Prenatal ultrasound demonstration of scoliosis, absence of one rib, a radial club
      hand, congenital heart defects and absent stomach in a fetus with VACTERL
      association.

PMID- 22482990
TI  - Primary fallopian tube carcinoma.

PMID- 22482991
TI  - Ruptured ovarian endometrioma.

PMID- 22482992
TI  - Ovarian cancer presenting as an acute abdomen was successfully diagnosed and
      managed by laparoscopy.

PMID- 22482993
TI  - Third- and fourth-degree perineal laceration in vaginal delivery.

PMID- 22482994
TI  - Highly efficient synthesis of a class of novel chiral-bridged atropisomeric
      monophosphine ligands via simple desymmetrization and their applications in
      asymmetric Suzuki-Miyaura coupling reaction.
AB  - A series of novel chiral-bridged atropisomeric monophosphine ligands were
      synthesized via convenient and simple pathways. The prepared ligands, especially
      for ligand 7d, were found to be highly effective in the Pd-catalyzed Suzuki
      Miyaura coupling reaction. The steric hindrance and electronic effect of
      substrates on the reactivity and enantioselectivity were explored preliminarily.

PMID- 22482995
TI  - Band-gap engineering via tailored line defects in boron-nitride nanoribbons,
      sheets, and nanotubes.
AB  - We perform a comprehensive study of the effects of line defects on electronic and
      magnetic properties of monolayer boron-nitride (BN) sheets, nanoribbons, and
      single-walled BN nanotubes using first-principles calculations and Born
      Oppenheimer quantum molecular dynamic simulation. Although line defects divide
      the BN sheet (or nanotube) into domains, we show that certain line defects can
      lead to tailor-made edges on BN sheets (or imperfect nanotube) that can
      significantly reduce the band gap of the BN sheet or nanotube. In particular, we
      find that the line-defect-embedded zigzag BN nanoribbons (LD-zBNNRs) with
      chemically homogeneous edges such as B- or N-terminated edges can be realized by
      introducing a B(2), N(2), or C(2) pentagon-octagon-pentagon (5-8-5) line defect
      or through the creation of the antisite line defect. The LD-zBNNRs with only B
      terminated edges are predicted to be antiferromagnetic semiconductors at the
      ground state, whereas the LD-zBNNRs with only N-terminated edges are metallic
      with degenerated antiferromagnetic and ferromagnetic states. In addition, we find
      that the hydrogen-passivated LD-zBNNRs as well as line-defect-embedded BN sheets
      (and nanotubes) are nonmagnetic semiconductors with markedly reduced band gap.
      The band gap reduction is attributed to the line-defect-induced impurity states.
      Potential applications of line-defect-embedded BN nanomaterials include
      nanoelectronic and spintronic devices.

PMID- 22482997
TI  - Image-based characterization of thrombus formation in time-lapse DIC microscopy.
AB  - The characterization of thrombus formation in time-lapse DIC microscopy is of
      increased interest for identifying genes which account for atherothrombosis and
      coronary artery diseases (CADs). In particular, we are interested in large-scale
      studies on zebrafish, which result in large amount of data, and require automatic
      processing. In this work, we present an image-based solution for the automatized
      extraction of parameters quantifying the temporal development of thrombotic
      plugs. Our system is based on the joint segmentation of thrombotic and aortic
      regions over time. This task is made difficult by the low contrast and the high
      dynamic conditions observed in vivo DIC microscopic scenes. Our key idea is to
      perform this segmentation by distinguishing the different motion patterns in
      image time series rather than by solving standard image segmentation tasks in
      each image frame. Thus, we are able to compensate for the poor imaging
      conditions. We model motion patterns by energies based on the idea of dynamic
      textures, and regularize the model by two prior energies on the shape of the
      aortic region and on the topological relationship between the thrombus and the
      aorta. We demonstrate the performance of our segmentation algorithm by
      qualitative and quantitative experiments on synthetic examples as well as on real
      in vivo microscopic sequences.

PMID- 22482998
TI  - The future of nursing for emergency care.

PMID- 22482996
TI  - Quantitative 1H NMR. Development and potential of an analytical method: an
      update.
AB  - Covering the literature from mid-2004 until the end of 2011, this review
      continues a previous literature overview on quantitative (1)H NMR (qHNMR)
      methodology and its applications in the analysis of natural products. Among the
      foremost advantages of qHNMR is its accurate function with external calibration,
      the lack of any requirement for identical reference materials, a high precision
      and accuracy when properly validated, and an ability to quantitate multiple
      analytes simultaneously. As a result of the inclusion of over 170 new references,
      this updated review summarizes a wealth of detailed experiential evidence and
      newly developed methodology that supports qHNMR as a valuable and unbiased
      analytical tool for natural product and other areas of research.

PMID- 22482999
TI  - Managing patient flow with triage streaming to identify patients for Dutch
      emergency nurse practitioners.
AB  - INTRODUCTION: We developed a stream system to the current triangle system in
      order to manage patient flow at the emergency department and to clarify ENP role
      boundaries. METHODS: Data on admission and death rates--indicating injury
      severity--and data on length of stay--indicating resource utilisation--were
      collected from 48,397 patients triaged in the Netherlands in 2009. RESULTS: A
      total of 24,294 (50.2%) patients were triaged as 'suitable for treatment by an
      ENP' (ENP-stream). Remaining patients were triaged 'medium care' or 'high care'.
      In the medium and high care groups, significantly more admissions took place
      (6100, 25.3%) and significantly more patients died (31, 0.1%) compared to the
      patient group in the ENP-stream (admissions: 840, 3.5%, p<0.001 and deaths 0,
      0.0%, p<0.001). The ENP-streaming is an accurate predictor of not needing to be
      admitted (PPV=97%) and of ED survival (PPV=100%). Mean length of stay was
      significantly shorter for patients in the ENP-stream compared to the other
      patients (back transformed values: 74 vs. 147 min, p<0.001). CONCLUSION: This
      study showed excellent correlation between the ENP-streaming and patients' injury
      severity and resource utilisation, suggesting high internal validity of our
      triage streaming system. It clarifies the ENP role, minimising the subjectivity
      of patient allocation.

PMID- 22483000
TI  - The everyday work at a Swedish emergency department--the practitioners'
      perspective.
AB  - In the everyday work at emergency departments (EDs), the patients being cared for
      have different needs and perceived symptoms. To meet their need for emergency
      care, knowledge of the work is important. The aim of this study is to explore the
      everyday work at a Swedish ED from a practitioner's perspective. METHOD: This
      study has a qualitative, exploratory design with observations and interviews at
      two EDs. Data were analysed by content analysis. FINDINGS: The everyday work is
      characterised by a rapid, short and standardised encounter with limited scope to
      provide individualised care, which leads to a mechanical approach. It is also
      characterised by an adaptive approach in which practitioners strive to be
      adaptable by structuring everyday work and cooperation to achieve a good
      workflow. CONCLUSIONS: The study shows that the practitioners' encounter with
      patients and relatives is rapid and of limited duration. The care activities that
      practitioners mainly perform comprise standard medical management and are
      performed more mechanically than in a caring way. The practitioners strive to
      balance the requirements and the realisation of the everyday work through
      structures and in cooperation with other practitioners, although they work more
      in parallel than in integrated teams.

PMID- 22483001
TI  - Violence in the emergency department: an ethnographic study (part I).
AB  - Violence in the emergency department (ED) is a significant problem and it is
      increasing. Nevertheless the problem remains inadequately investigated as most
      studies that have investigated this issue are descriptive in nature. Although
      these studies have provided important preliminary information, they fail to
      reveal the complexities of the problem, in particular the cultural aspects of
      violence which are crucial for the ED. This paper is part I of a 2-part series
      which will provide an overview of the background, aims and methods of an
      ethnographic study about violence in the ED. The study aimed to explore the
      cultural aspects of violence in the ED. Contemporary ethnography was adopted to
      frame the study's methodology. The study was carried out at a major metropolitan
      ED over 3 months using observations, questionnaires and interviews. Initially,
      the questionnaires were analysed using SPSS before incorporating into the
      qualitative data. Then, a data analysis framework was adopted to assist in the
      analysis of data at item (domain), pattern (taxonomic and componential) and
      structural levels. A brief description of the cultural scene will also be
      highlighted before leaving the findings of the study along with its discussions
      to the part II of the 2-part series.

PMID- 22483002
TI  - Group supervision as a means of developing professional competence within pre
      hospital care.
AB  - BACKGROUND: Ambulance care has its foundations in experience-based knowledge
      relating to the care provider's flexibility and humility in the encounter with
      patients. The group supervision model used in this study is retrospective and
      experience orientated and it is designed to promote and develop the group's
      overall competence by facilitating the group process, as well as extending and
      improving levels of professional knowledge. AIM: The aim was to evaluate the
      experience of group supervision and to explore its impact on the participants'
      personal and professional development. METHOD: This study uses an inductive
      qualitative approach where data collection was performed in the form of a focus
      group interview and analysed by a model of content analysis. CONCLUSION: Group
      supervision appears to have had a positive impact on the participants' personal
      and professional development. The structure of the model appears to make it
      easier for the inexperienced co-worker more rapidly to develop expertise within
      his/her working area, which can be seen as an important tool in today's
      financially focused and time-pressurised health-care service. It is to be hoped
      that the results of this study will interest health managers and encourage them
      to consider group supervision as a tool for professional development not only
      within the area of the ambulance service.

PMID- 22483003
TI  - Pre-hospital pain management patterns and triage nurse documentation.
AB  - INTRODUCTION: Little is known about the public's preferences for pain management
      prior to attending an Emergency Department (ED). Therefore, the aim of the study
      was to explore (i) triage documentation of pre-hospital analgesic patterns for
      patients presenting in pain; (ii) patient documented explanations for not self
      administering an analgesic in the pre-hospital setting; (iii) triage nurse
      documentation of pain descriptors and or pain scores; and (iv) the disposition of
      ED patients presenting in pain. METHOD: A 2-week retrospective exploratory review
      was conducted. RESULTS: There were 2142 ED presentations during the 2-week study
      and 52% of patients had documented evidence of arriving with a painful condition.
      Of the 1113 patients 60% were documented to be in pain on arrival. Of the group
      documented to have arrived in pain only 28% self-administered or received an
      analgesic in the pre-hospital/community setting. Patients provided a variety of
      reasons for not self-administering a pre-hospital analgesic. CONCLUSION:
      Unnecessary suffering may be avoided if the public had a better understanding of
      pain and the benefits of pain management. Further research is required to better
      understand the beliefs and attitudes towards pain and pain management by
      clinicians and the public.

PMID- 22483004
TI  - The divided self: near death experiences of resuscitated patients--a review of
      literature.
AB  - This paper explores the prevalence of 'near death experience' phenomena
      associated with a resuscitation event and examines the current state of evidence
      for causation. Patients' reports of unusual recollections associated with a
      period of unconsciousness (perceived as approaching death) have fascinated
      individuals and the medical fraternity. Near death experiences (NDE) are reported
      in 4-9% of general community members and up to 23% of critical illness patients,
      although they can occur in healthy individuals who may think they are in peril.
      One explanation is that paranormal visions that include seeing bright lights, a
      tunnel and having feelings of peace may be a stage of enlightenment as death
      approaches. More objective explanations point to neuro-chemical changes in a
      stressed or dying brain as explanation for nearly all the elements of near death
      experience. However if this is so, NDE should occur in all patients who are
      critically ill and near death. In general, patients report positive psychological
      outcomes after a near death experience. Nurses can support patients during a time
      of crisis by assisting them and their families to comprehend the experiential
      event using effective communication and listening skill.

PMID- 22483005
TI  - Improving the safety of oxygen therapy in the treatment of acute myocardial
      infarctions.
AB  - AIM: The article examines the evidence for giving oxygen routinely to patients
      with suspected myocardial infarction, and addresses the challenges in changing
      practice. BACKGROUND: It has been thought that administering oxygen to patients
      suffering from acute myocardial infarctions may be beneficial, but there is a
      lack of supporting evidence. Furthermore there is evidence that the use of oxygen
      in some circumstances may not improve clinical outcome. Despite conflicting
      evidence, guidelines in the past have recommended supplementary oxygen as part of
      treatment. Therefore it was necessary to understand and identify best practice.
      METHODS: Evidence was collated using electronic databases. Search terms included
      'acute myocardial infarction' 'acute coronary syndrome' 'oxygen' and 'hypoxia',
      'hyperoxaemia'. CONCLUSION: A systematic review of studies did not confirm that
      the use of routine oxygen in the acute stages of a myocardial infarction reduces
      myocardial ischemia. In reality, some evidence suggests that oxygen may even
      increase myocardial ischemia. Therefore it is crucial that emergency care
      nurses/practitioners across the world use observation skills and monitoring such
      as pulse oximetry to recognise the clinical need for supplementary oxygen to be
      given to a patient.

PMID- 22483006
TI  - Nail gun may cause heart injury: a young adult's misadventure.
AB  - Penetrating cardiac and great vessels trauma is life threatening and a surgical
      challenge. We relate an unusual case of pulmonary artery injury secondary to an
      accidental trauma by a nail gun. Surgical repair was late but successful.

PMID- 22483007
TI  - Myasthenia gravis: a real emergency.

PMID- 22483009
TI  - Investigating the calculation of anharmonic vibrational frequencies using force
      fields derived from density functional theory.
AB  - The calculation of anharmonic vibrational frequencies for a set of small
      molecules has been examined to explore the merit of applying such computationally
      expensive approaches for large molecules with density functional theory. The
      performance of different hybrid and gradient-corrected exchange-correlation
      functionals has been assessed for the calculation of anharmonic vibrational
      frequencies using second-order vibrational perturbation theory with two- and four
      mode couplings and compared to the recently developed transition optimized
      shifted Hermite method. A range of exchange-correlation functionals (B3LYP, BLYP,
      EDF1, EDF2, B97-1, B97-2, HCTH-93, HCTH-120, HCTH-147, and HCTH-407) have been
      evaluated with reference to a large experimental data set comprising 88 species
      and 655 modes as well as a smaller set of shifts in frequency because of
      anharmonicity derived from experimental data. The anharmonic frequencies
      calculated using hybrid functionals provide the best agreement with experiment,
      and are not significantly improved by frequency scaling factors, indicating an
      absence of significant systematic error. For the molecules studied, the B97-1 and
      B97-2 functionals give the closest overall agreement with experiment, although
      the improvement over the best case for pure harmonic frequencies is modest.
      Predictions of the experimental anharmonic shifts are closest for the B3LYP and
      EDF2 functionals, with B97-1 performing well because of a good description of the
      harmonic force field. Investigations using modified hybrid functionals with
      increased fractions of Hartree-Fock exchange indicate that approximately 20%
      Hartree-Fock exchange is optimal.

PMID- 22483010
TI  - Molecular modeling of the relationship between nanoparticle shape anisotropy and
      endocytosis kinetics.
AB  - In this work, an N-varied dissipative particle dynamics (DPD) simulation
      technique is applied to investigate detailed endocytosis kinetics for ligand
      coated nanoparticles with different shapes, including sphere-, rod- and disk
      shaped nanoparticles. Our results indicate that the rotation of nanoparticles,
      which is one of the most important mechanisms for endocytosis of shaped
      nanoparticle, regulates the competition between ligand-receptor binding and
      membrane deformation. Shape anisotropy of nanoparticles divides the whole
      internalization process into two stages: membrane invagination and nanoparticle
      wrapping. Due to the strong ligand-receptor binding energy, the membrane
      invagination stage is featured by the rotation of nanoparticles to maximize their
      contact area with the membrane. While the kinetics of the wrapping stage is
      mainly dominated by the part of nanoparticles with the largest local mean
      curvature, at which the membrane is most strongly bent. Therefore, nanoparticles
      with various shapes display different favorable orientations for the two stages,
      and one or two orientation rearrangement may be required during the endocytosis
      process. Our simulation results also demonstrate that the shape anisotropy of
      nanoparticles generates a heterogeneous membrane curvature distribution and might
      break the symmetry of the internalization pathway, and hence induce an asymmetric
      endocytosis.

PMID- 22483011
TI  - Towards whole-body imaging at the single cell level using ultra-sensitive stem
      cell labeling with oligo-arginine modified upconversion nanoparticles.
AB  - Mesenchymal stem cells (MSCs) have shown great potential in regenerative
      medicine. Sensitive and reliable methods for stem cell labeling and in vivo
      tracking are thus of great importance. Herein, we report the use of upconversion
      nanoparticles (UCNPs) as an exogenous contrast agent to track mouse MSCs (mMSCs)
      in vivo. To improve the labeling efficiency, oligo-arginine is conjugated to
      polyethylene glycol (PEG) coated UCNPs to enhance the nanoparticles uptake by
      mMSCs. Systematic in vitro tests reveal that the proliferation and
      differentiation of mMSCs are not notably affected by UCNP-labeling, suggesting
      that the labeled cells are able to maintain their stem cell potency. No apparent
      exocytosis is found in our in vitro labeling experiment by using a transwell
      culture system over a course of 10 days, indicating the potential capability of
      using our UCNP-labeling method for long-term stem cell tracking. To demonstrate
      the tracking sensitivity of our stem cell labeling approach, UCNP-labeled mMSCs
      are subcutaneously transplanted into mice and imaged using an in vivo
      upconversion luminescence (UCL) imaging system. As few as ~10 cells labeled with
      UCNPs are detected in vivo, evidencing a remarkable improvement in detection
      sensitivity of our UCNP-labeled hMSCs compared with other stem cell labeling
      techniques using conventional exogenous agents. We further track UCNP-labeled
      mMSCs after intravenous injection, and observe the translocation of mMSCs from
      lung where they initially accumulate, to liver, a phenomenon consistent to
      previous reports. Our results highlight the promise of using UCNPs as a new type
      of ultra-sensitive probes for labeling and in vivo tracking of stem cells at
      nearly the single cell level.

PMID- 22483013
TI  - High spin Co(I): high-frequency and -field EPR spectroscopy of CoX(PPh3)3 (X =
      Cl, Br).
AB  - The previously reported pseudotetrahedral Co(I) complexes, CoX(PR(3))(3), where R
      = Me, Ph, and chelating analogues, and X = Cl, Br, I exhibit a spin triplet
      ground state, which is uncommon for Co(I), although expected for this geometry.
      Described here are studies using electronic absorption and high-frequency and 
      field electron paramagnetic resonance (HFEPR) spectroscopy on two members of this
      class of complexes: CoX(PR(3))(3), where R = Ph and X = Cl and Br. In both cases,
      well-defined spectra corresponding to axial spin triplets were observed, with
      signals assignable to three distinct triplet species, and with perfectly axial
      zero-field splitting (zfs) given by the parameter D = +4.46, +5.52, +8.04 cm(-1),
      respectively, for CoCl(PPh(3))(3). The crystal structure reported for
      CoCl(PPh(3))(3) shows crystallographic 3-fold symmetry, but with three
      structurally distinct molecules per unit cell. Both of these facts thus correlate
      with the HFEPR data. The investigated complexes, along with a number of
      structurally characterized Co(I) trisphosphine analogues, were analyzed by
      quantum chemistry calculations (both density functional theory (DFT) and
      unrestricted Hartree-Fock (UHF) methods). These methods, along with ligand-field
      theory (LFT) analysis of CoCl(PPh(3))(3), give reasonable agreement with the
      salient features of the electronic structure of these complexes. A spin triplet
      ground state is strongly favored over a singlet state and a positive, axial D
      value is predicted, in agreement with experiment. Quantitative agreement between
      theory and experiment is less than ideal with LFT overestimating the zfs, while
      DFT underestimates these effects. Despite these shortcomings, this study
      demonstrates the ability of advanced paramagnetic resonance techniques, in
      combination with other experimental techniques, and with theory, to shed light on
      the electronic structure of an unusual transition metal ion, paramagnetic Co(I).

PMID- 22483012
TI  - Chitosan-based scaffolds for the support of smooth muscle constructs in
      intestinal tissue engineering.
AB  - Intestinal tissue engineering is an emerging field due to a growing demand for
      intestinal lengthening and replacement procedures secondary to massive resections
      of the bowel. Here, we demonstrate the potential use of a chitosan/collagen
      scaffold as a 3D matrix to support the bioengineered circular muscle constructs
      maintain their physiological functionality. We investigated the biocompatibility
      of chitosan by growing rabbit colonic circular smooth muscle cells (RCSMCs) on
      chitosan-coated plates. The cells maintained their spindle-like morphology and
      preserved their smooth muscle phenotypic markers. We manufactured tubular
      scaffolds with central openings composed of chitosan and collagen in a 1:1 ratio.
      Concentrically aligned 3D circular muscle constructs were bioengineered using
      fibrin-based hydrogel seeded with RCSMCs. The constructs were placed around the
      scaffold for 2 weeks, after which they were taken off and tested for their
      physiological functionality. The muscle constructs contracted in response to
      acetylcholine (Ach) and potassium chloride (KCl) and they relaxed in response to
      vasoactive intestinal peptide (VIP). These results demonstrate that chitosan is a
      biomaterial possibly suitable for intestinal tissue engineering applications.

PMID- 22483014
TI  - Target-focused exercise regime: a motivational strategy to improve patient's
      adherence to treatment of a stiff thumb interphalangeal joint.

PMID- 22483015
TI  - ApoA-1 infusion reduces arterial cholesterol and myocardial lesions in a rat
      model of cardiac dysfunction and insulin resistance.
AB  - OBJECTIVE: Low plasma high-density lipoprotein cholesterol (HDL-C) concentration
      is associated with the metabolic syndrome (MetS) and increased prevalence of
      cardiovascular disease (CVD). Animal and human studies report infusion of
      apolipoprotein A-1 (apoA-1) can reduce endothelial dysfunction, and/or induce
      regression of atherosclerosis. However, the direct mechanisms underlying the
      vascular benefits of either apoA-1 or HDL-C remain unclear. In this study, we
      assessed the ability of reconstituted HDL (rHDL) to improve vascular
      complications of MetS, including left ventricular (LV)-hypertrophy, arterial
      cholesterol deposition and myocardial lesion development. METHODS AND RESULTS:
      Obese insulin resistant (IR) JCR:LA-cp rats were infused with rHDL (0.4 mg/kg)
      over 3 days before assessing cardiac function (Echocardiography) at days 7 and 50
      post-infusion, as well as haematoxylin and eosin staining of myocardial lesions
      at day 50. Acute ex vivo arterial cholesterol deposition was assessed with acute
      infusion of rHDL ex-vivo. Infusion of rHDL partially corrected abnormal diastolic
      compliance (18%; *p<0.05) and improved parameters of cardiac function in IR rats.
      Further, acute rHDL infusion in carotid vessels reduced remnant lipoprotein
      associated-cholesterol deposition (30-86%; **p<0.01) ex vivo in IR and male
      Wistar rats and reduced (41%; *p<0.05) the frequency of early-stage myocardial
      lesions in IR rats. CONCLUSION: Short-term infusion of rHDL may beneficially
      reduce chronic vascular sequelae of MetS, including temporary improvement in LV
      dysfunction, acute reduction of acute arterial cholesterol deposition and the
      development of early-stage myocardial lesions in the JCR:LA-cp rat.

PMID- 22483016
TI  - [Osteoporosis in liver cirrhosis].
AB  - Osteoporosis is a common complication of chronic liver disease, especially in the
      final stages. This entity is more critical in liver transplant recipients, when
      bone loss accelerates during the immediate postoperative period. The main
      mechanism involved in the development of osteoporosis in liver disease is
      deficient bone formation due to the harmful effects of substances such as
      bilirubin and bile acids or the toxic effect of alcohol or iron on osteoblasts.
      To prevent and treat osteoporosis, good nutrition and calcium and vitamin D
      supplementation are required. There are no specific recommendations on drug
      treatment but bisphosphonates are effective in increasing bone mass in patients
      with chronic cholestasis and have a good safety profile.

PMID- 22483017
TI  - [Leiomyoma in Meckel's diverticulum].
AB  - Meckel's diverticulum (MD) is a persistent embryonic remnant occurring in 2% of
      the general population. This entity is usually clinically silent and is only
      discovered when complications occur. Diagnosis is rarely made preoperatively.
      Surgical resection of symptomatic MD is widely accepted but the most appropriate
      management of asymptomatic MD remains unclear. We present a case of MD that
      summarizes some of the complications that may occur. The peculiarity of this case
      was that the complications were caused by a leiomyoma. The presence of tumoral
      disease in MD accounts for 3.2% of complications. The most common neoplasm is
      carcinoid tumor. Few publications have reported benign neoplasms in MD, probably
      due to their low incidence.

PMID- 22483018
TI  - Catastrophic neglect of the basic sciences in medicine.

PMID- 22483019
TI  - Psychiatry's identity crisis.

PMID- 22483020
TI  - Protocols for uncontrolled donation after circulatory death.

PMID- 22483022
TI  - Christine Petit: interdisciplinary geneticist.

PMID- 22483023
TI  - Effect of population-based screening on breast cancer mortality.

PMID- 22483024
TI  - Effect of population-based screening on breast cancer mortality.

PMID- 22483025
TI  - Effect of population-based screening on breast cancer mortality.

PMID- 22483027
TI  - Effect of population-based screening on breast cancer mortality.

PMID- 22483028
TI  - Adverse operative outcomes in patients with anaemia.

PMID- 22483030
TI  - Adverse operative outcomes in patients with anaemia.

PMID- 22483031
TI  - NICE response to World Report on epilepsy guidance.

PMID- 22483032
TI  - An autoimmune double attack.

PMID- 22483033
TI  - Stigonemapeptin, an Ahp-containing depsipeptide with elastase inhibitory activity
      from the bloom-forming freshwater cyanobacterium Stigonema sp.
AB  - Stigonemapeptin (1), a depsipeptide containing an Ahp (3-amino-6-hydroxy-2
      piperidone) residue, was isolated from a bloom sample of the freshwater
      cyanobacterium Stigonema sp. collected from North Nokomis Lake in the Highland
      Lake District of northern Wisconsin. The planar structure was determined by 1D
      and 2D NMR experiments as well as HRESIMS analysis. The absolute configurations
      of the amino acids were determined using the advanced Marfey's method after acid
      hydrolysis. Stigonemapeptin (1), characterized by the presence of the Ahp
      residue, also contained the modified amino acids Abu (2-amino-2-butenoic acid)
      and N-formylated Pro. Stigonemapeptin (1) showed in vitro elastase and
      chymotrypsin inhibitory activity, with IC(50) values of 0.26 and 2.93 MUM,
      respectively.

PMID- 22483034
TI  - Reversible hydrogen transfer reactions in thiyl radicals from cysteine and
      related molecules: absolute kinetics and equilibrium constants determined by
      pulse radiolysis.
AB  - The mercapto group of cysteine (Cys) is a predominant target for oxidative
      modification, where one-electron oxidation leads to the formation of Cys thiyl
      radicals, CysS(*). These Cys thiyl radicals enter 1,2- and 1,3-hydrogen transfer
      reactions, for which rate constants are reported in this paper. The products of
      these 1,2- and 1,3-hydrogen transfer reactions are carbon-centered radicals at
      position C(3) (alpha-mercaptoalkyl radicals) and C(2) ((*)C(alpha) radicals) of
      Cys, respectively. Both processes can be monitored separately in Cys analogues
      such as cysteamine (CyaSH) and penicillamine (PenSH). At acidic pH, thiyl
      radicals from CyaSH permit only the 1,2-hydrogen transfer according to
      equilibrium 12, (+)H(3)NCH(2)CH(2)S(* )? (+)H(3)NCH(2)(*)CH-SH, where rate
      constants for forward and reverse reaction are k(12) ~ 10(5) s(-1) and k(-12) ~
      1.5 * 10(5)s(-1), respectively. In contrast, only the 1,3-hydrogen transfer is
      possible for thiyl radicals from PenSH according to equilibrium 14,
      ((+)H(3)N/CO(2)H)C(alpha)-C(CH(3))(2)-S(*) ? ((+)H(3)N/CO(2)H)(*)C(alpha)
      C(CH(3))(2)-SH, where rate constants for the forward and the reverse reaction are
      k(14) = 8 * 10(4) s(-1) and k(-14) = 1.4 * 10(6) s(-1). The (*)C(alpha) radicals
      from PenSH and Cys have the additional opportunity for beta-elimination of
      HS(*)/S(*-), which proceeds with k(39) ~ (3 +/- 1) * 10(4) s(-1) from (*)C(alpha)
      radicals from PenSH and k(-34) ~ 5 * 10(3) s(-1) from (*)C(alpha) radicals from
      Cys. The rate constants quantified for the 1,2- and 1,3-hydrogen transfer
      reactions can be used as a basis to calculate similar processes for Cys thiyl
      radicals in proteins, where hydrogen transfer reactions, followed by the addition
      of oxygen, may lead to the irreversible modification of target proteins.

PMID- 22483035
TI  - Nanoscale mid-infrared evaluation of the miscibility behavior of blends of
      dextran or maltodextrin with poly(vinylpyrrolidone).
AB  - Determining the extent of miscibility of amorphous components is of great
      importance for certain pharmaceutical systems, in particular for polymer-polymer
      and polymer-small molecule blends. In this study, the application of standard
      atomic force microscopy (AFM) measurements combined with nanoscale mid-infrared
      (mid-IR) spectroscopy was explored to evaluate miscibility in binary polymer
      blends. The miscibility characteristics of a set of 50/50 (w/w) polymer blends
      comprising of poly(vinylpyrrolidone) (PVP) with dextran or maltodextrin (DEX) of
      varying molecular weights (MWs) were investigated. Standard AFM characterization
      results show good agreement with inferences drawn from differential scanning
      calorimetry (DSC) analysis in terms of forming either single or two phase
      systems. AFM analysis also provided insight into the microstructure of the two
      phase systems and how domain sizes varied as a function of polymer MWs. Nanoscale
      mid-IR evaluation of the blends, performed by collecting local mid-IR spectra or
      spectral maps, provided an extra dimension of information about the dependence of
      polymer MWs on chemical composition of the different phases. AFM, combined with
      nanoscale mid-infrared analysis, thus appears to be a promising technique for the
      evaluation of miscibility in certain pharmaceutical blends.

PMID- 22483036
TI  - Mechanical break junctions: enormous information in a nanoscale package.
AB  - Mechanical break junctions, particularly those in which a metal tip is repeatedly
      moved in and out of contact with a metal film, have provided many insights into
      electronic conduction at the atomic and molecular scale, most often by averaging
      over many possible junction configurations. This averaging throws away a great
      deal of information, and Makk et al. in this issue of ACS Nano demonstrate that,
      with both simulated and real experimental data, more sophisticated two
      dimensional analysis methods can reveal information otherwise obscured in simple
      histograms. As additional measured quantities come into play in break junction
      experiments, including thermopower, noise, and optical response, these more
      sophisticated analytic approaches are likely to become even more powerful. While
      break junctions are not directly practical for useful electronic devices, they
      are incredibly valuable tools for unraveling the electronic transport physics
      relevant for ultrascaled nanoelectronics.

PMID- 22483037
TI  - Nicotine-induced changes of brain beta-endorphin.
AB  - A consensus has emerged that endogenous opioid peptides and their receptors play
      an important role in the psychoactive properties of nicotine. Although behavioral
      studies have shown that beta-endorphin contributes to the rewarding and emotional
      effects of nicotine, whether the drug alters the function of brain endorphinergic
      neurons is not fully explored. These studies investigated the effect of acute,
      1mg/kg, sc, and chronic, daily injection of 1mg/kg, sc, for 14 days,
      administration of free base nicotine on brain beta-endorphin and its precursor
      proopiomelanocortin (POMC). Acute and chronic treatment with nicotine decreased
      beta-endorphin content in hypothalamus, the principal site of beta-endorphin
      producing neurons in the brain, and in the endorphinergic terminal fields in
      striatum and hippocampus. The acute effect of nicotine on beta-endorphin was
      reversed by the nicotinic antagonist mecamylamine and the dopamine antagonist
      haloperidol, indicating pharmacological specificity and involvement of dopamine
      D2-like receptors. Similar observations were made in prefrontal cortex. POMC mRNA
      in hypothalamus and prefrontal cortex was unchanged following acute nicotine, but
      it decreased moderately with chronic treatment. The nicotine treatments had no
      effect on pituitary and plasma beta-endorphin. Taken together, these results
      could be interpreted to indicate that nicotine alters the synthesis and release
      of beta-endorphin in the limbic brain in vivo. Altered endorphinergic function
      may contribute to the behavioral effects of acute and chronic nicotine treatment
      and play a role in nicotine addiction.

PMID- 22483038
TI  - OH-initiated heterogeneous aging of highly oxidized organic aerosol.
AB  - The oxidative evolution ("aging") of organic species in the atmosphere is thought
      to have a major influence on the composition and properties of organic
      particulate matter but remains poorly understood, particularly for the most
      oxidized fraction of the aerosol. Here we measure the kinetics and products of
      the heterogeneous oxidation of highly oxidized organic aerosol, with an aim of
      better constraining such atmospheric aging processes. Submicrometer particles
      composed of model oxidized organics-1,2,3,4-butanetetracarboxylic acid
      (C(8)H(10)O(8)), citric acid (C(6)H(8)O(7)), tartaric acid (C(4)H(6)O(6)), and
      Suwannee River fulvic acid-were oxidized by gas-phase OH in a flow reactor, and
      the masses and elemental composition of the particles were monitored as a
      function of OH exposure. In contrast to our previous studies of less-oxidized
      model systems (squalane, erythritol, and levoglucosan), particle mass did not
      decrease significantly with heterogeneous oxidation. Carbon content of the
      aerosol always decreased somewhat, but this mass loss was approximately balanced
      by an increase in oxygen content. The estimated reactive uptake coefficients of
      the reactions range from 0.37 to 0.51 and indicate that such transformations
      occur at rates corresponding to 1-2 weeks in the atmosphere, suggesting their
      importance in the atmospheric lifecycle of organic particulate matter.

PMID- 22483039
TI  - Adjunct primer for the use of national comprehensive cancer network guidelines
      for the surgical management of cutaneous malignant melanoma patients.
AB  - Recently, a Surveillance Epidemiology and End Results (SEER) survey of melanoma
      patterns of care by the Mayo Clinic, Scottsdale showed remarkable deviations from
      best practice patterns throughout the country. The study, which analyzed the SEER
      records of 35,126 stage I to III cutaneous malignant melanoma patients treated
      from 2004 to 2006, showed that adherence to National Comprehensive Cancer Network
      (NCCN) therapeutic resection margins occurred in less than 36% of patients.
      Similarly, considerable variation in the quality of melanoma care in the United
      States when assessed using 26 quality indicators drawn by a panel of melanoma
      experts was independently reported. These observations underscore the significant
      lack of adherence to published best practice patterns reflected by the NCCN
      guidelines. The untoward effects of these variations in practice pattern can have
      an inordinate impact on the survival of melanoma patients in whom long term
      outcomes are affected by the adequacy of surgical management. Thin malignant
      melanoma is curable; however, thick or node positive melanoma is often incurable.
      This outcome is determined not only by the stage at presentation but by the use
      of best practice patterns as reflected in current NCCN cutaneous melanoma
      practice guidelines.

PMID- 22483040
TI  - Regulation of the stress response by the gut microbiota: implications for
      psychoneuroendocrinology.
AB  - There is now an expanding volume of evidence to support the view that commensal
      organisms within the gut play a role in early programming and later responsivity
      of the stress system. The gut is inhabited by 1013-1014 micro-organisms, which is
      ten times the number of cells in the human body and contains 150 times as many
      genes as our genome. It has long been recognised that gut pathogens such as
      Escherichia coli, if they enter the gut can activate the HPA. However, animals
      raised in a germ-free environment show exaggerated HPA responses to psychological
      stress, which normalises with monocolonisation by certain bacterial species
      including Bifidobacterium infantis. Moreover, increased evidence suggests that
      animals treated with probiotics have a blunted HPA response. Stress induces
      increased permeability of the gut allowing bacteria and bacterial antigens to
      cross the epithelial barrier and activate a mucosal immune response, which in
      turn alters the composition of the microbiome and leads to enhanced HPA drive.
      Increasing data from patients with irritable bowel syndrome and major depression
      indicate that in these syndromes alteration of the HPA may be induced by
      increased gut permeability. In the case of irritable bowel syndrome the increased
      permeability can respond to probiotic therapy. Detailed prospective studies in
      patients with mood disorders examining the gut microbiota, immune parameters and
      HPA activity are required to throw further light on this emerging area. It is
      however clear that the gut microbiota must be taken into account when considering
      the factors regulating the HPA.

PMID- 22483042
TI  - Compressed sensing, sparsity, and dimensionality in neuronal information
      processing and data analysis.
AB  - The curse of dimensionality poses severe challenges to both technical and
      conceptual progress in neuroscience. In particular, it plagues our ability to
      acquire, process, and model high-dimensional data sets. Moreover, neural systems
      must cope with the challenge of processing data in high dimensions to learn and
      operate successfully within a complex world. We review recent mathematical
      advances that provide ways to combat dimensionality in specific situations. These
      advances shed light on two dual questions in neuroscience. First, how can we as
      neuroscientists rapidly acquire high-dimensional data from the brain and
      subsequently extract meaningful models from limited amounts of these data? And
      second, how do brains themselves process information in their intrinsically high
      dimensional patterns of neural activity as well as learn meaningful,
      generalizable models of the external world from limited experience?

PMID- 22483041
TI  - Central and peripheral circadian clocks in mammals.
AB  - The circadian system of mammals is composed of a hierarchy of oscillators that
      function at the cellular, tissue, and systems levels. A common molecular
      mechanism underlies the cell-autonomous circadian oscillator throughout the body,
      yet this clock system is adapted to different functional contexts. In the central
      suprachiasmatic nucleus (SCN) of the hypothalamus, a coupled population of
      neuronal circadian oscillators acts as a master pacemaker for the organism to
      drive rhythms in activity and rest, feeding, body temperature, and hormones.
      Coupling within the SCN network confers robustness to the SCN pacemaker, which in
      turn provides stability to the overall temporal architecture of the organism.
      Throughout the majority of the cells in the body, cell-autonomous circadian
      clocks are intimately enmeshed within metabolic pathways. Thus, an emerging view
      for the adaptive significance of circadian clocks is their fundamental role in
      orchestrating metabolism.

PMID- 22483043
TI  - Decision-related activity in sensory neurons: correlations among neurons and with
      behavior.
AB  - Neurons in early sensory cortex show weak but systematic correlations with
      perceptual decisions when trained animals perform at psychophysical threshold.
      These correlations are observed across repeated presentations of identical
      stimuli and cannot be explained by variation in external factors. The
      relationship between the activity of individual sensory neurons and the animal's
      behavioral choice means that even neurons in early sensory cortex carry
      information about an upcoming decision. This relationship, termed choice
      probability, may reflect the effect of fluctuations in neuronal firing rate on
      the animal's decision, but it can also reflect modulation of sensory responses by
      cognitive factors, or network properties such as variability that is shared among
      populations of neurons. Here, we review recent work clarifying the relationship
      among fluctuations in the responses of individual neurons, correlated
      variability, and behavior in a variety of tasks and cortical areas. We also
      discuss the possibility that choice probability may in part reflect the influence
      of cognitive factors on sensory neurons and explore the situations in which
      choice probability can be used to make inferences about the role of particular
      sensory neurons in the decision-making process.

PMID- 22483046
TI  - The feruloyl esterase gene family of Fusarium graminearum is differentially
      regulated by aromatic compounds and hosts.
AB  - Feruloyl esterases can liberate ferulic acid (FA) from plant cell wall polymers.
      They are expressed by plant pathogenic fungi and could play a role in
      pathogenicity, although this question has not been addressed yet. The fungus
      Fusarium graminearum is the principal causal agent of fusarium head blight (FHB)
      and gibberella ear rot (GER), major diseases of wheat, barley, and maize in all
      temperate regions of the world. The F. graminearum genome contains seven genes
      with strong homology to feruloyl esterase (FAE) sequences. Phylogenetic analysis
      showed that these included three type B, three type C, and one type D FAE genes.
      Expression profiling of the seven FAE genes showed complex regulation patterns
      unique to each gene. In F. graminearum-infected plant tissues, the FAE genes
      exhibited host-specific gene expression. On wheat, FAEB1 and FAED1 were strongly
      expressed while FAEB2, FAEB3, and FAEC1 were expressed at more modest levels. On
      maize, only FAEB3, FAEC1, and FAED1 were expressed and at low levels. When
      growing F. graminearum in liquid culture, only FAEB1 and FAEC1 were expressed.
      Both genes were induced by a small group of related aromatic compounds including
      FA, caffeic acid, and p-coumaric acid. FAEB1 was induced by xylose, while
      repressed by glucose and galactose. FAEC1 was constitutively expressed at low
      levels in the presence of those sugars. Expression of the other five FAE genes
      was not detected in the culture conditions used. To determine if FAE genes were
      important for pathogenicity of F. graminearum, mutant strains inactivated for
      faeB1?, faeD1? or both genes were constructed and tested on wheat plants. No
      statistically significant change in pathogenicity and no compensatory expression
      of the other FAE genes were observed in the fae gene mutants. Our results show
      that FAEB1 and FAED1 are not required for pathogenicity of F. graminearum on
      wheat.

PMID- 22483045
TI  - Are communities of microbial symbionts more diverse than communities of macrobial
      hosts?
AB  - In this study, fungal viruses (mycoviruses) of plant-associated fungi were used
      to test the general assertion that communities of parasitic and mutualistic
      symbionts may be more species-diverse than communities of their hosts.
      Mycoviruses are poorly studied in general, but can affect the fitness and ecology
      of the fungi and plants with which they associate. To date, mycovirus incidence
      and diversity in natural communities remain largely unaddressed. Here, we
      compared the incidence and diversity of fungi associated with tallgrass prairie
      plants to the diversity and incidence of mycoviruses within those fungi.
      Specifically, we sampled viruses from fungi associated with a parasitic plant
      (Cuscuta cuspidata) and its most frequent host plant (Ambrosia psilostachya) in a
      tallgrass prairie habitat in Oklahoma. For each plant sample we cultured fungal
      endophytes from surface-sterilized above-ground tissues. From the cultured fungi
      we extracted DNA to identify fungi, and extracted double-stranded RNA (dsRNA) to
      detect mycoviruses. Mycoviruses were further characterized using reverse
      transcription-PCR and sequence analyses. We found at least 25 fungal taxa
      associated with the two plants, and 10 % of these fungi contained readily
      detectable viruses. Several mycovirus types were shared among fungal taxa,
      indicating that mycoviruses may be less specialized than originally thought.
      Although the virus community was not as diverse as the fungal endophyte community
      (16 taxa), species accumulation rates of mycoviruses (inferred from rescaled
      rarefaction curves) may be higher than those of their associated fungal hosts.
      Thus, mycoviruses represent a further layer of undocumented biodiversity in
      ecological communities.

PMID- 22483047
TI  - A molecular phylogeny of thermophilic fungi.
AB  - Sequences from 86 fungal genomes and from the two outgroup genomes Arabidopsis
      thaliana and Drosophila melanogaster were analyzed to construct a robust
      molecular phylogeny of thermophilic fungi, which are potentially rich sources of
      industrial enzymes. To provide experimental reference points, growth
      characteristics of 22 reported thermophilic or thermotolerant fungi, together
      with eight mesophilic species, were examined at four temperatures: 22  degrees C,
      34  degrees C, 45  degrees C, and 55  degrees C. Based on the relative growth
      performances, species with a faster growth rate at 45  degrees C than at 34 
      degrees C were classified as thermophilic, and species with better or equally
      good growth at 34  degrees C compared to 45  degrees C as thermotolerant. We
      examined the phylogenetic relationships of a diverse range of fungi, including
      thermophilic and thermotolerant species, using concatenated amino acid sequences
      of marker genes mcm7, rpb1, and rpb2 obtained from genome sequencing projects. To
      further elucidate the phylogenetic relationships in the thermophile-rich orders
      Sordariales and Eurotiales, we used nucleotide sequences from the nuclear
      ribosomal small subunit (SSU), the 5.8S gene with internal transcribed spacers 1
      and 2 (ITS 1 and 2), and the ribosomal large subunit (LSU) to include additional
      species for analysis. These phylogenetic analyses clarified the position of
      several thermophilic taxa. Thus, Myriococcum thermophilum and Scytalidium
      thermophilum fall into the Sordariales as members of the Chaetomiaceae,
      Thermomyces lanuginosus belongs to the Eurotiales, Malbranchea cinnamomea is a
      member of the Onygenales, and Calcarisporiella thermophila is assigned to the
      basal fungi close to the Mucorales. The mesophilic alkalophile Acremonium
      alcalophilum clusters with Verticillium albo-atrum and Verticillium dahliae,
      placing them in the recently established order Glomerellales. Taken together,
      these data indicate that the known thermophilic fungi are limited to the
      Sordariales, Eurotiales, and Onygenales in the Ascomycota and the Mucorales with
      possibly an additional order harbouring C. thermophila in the basal fungi. No
      supporting evidence was found for thermophilic species belonging to the
      Basidiomycota.

PMID- 22483044
TI  - The pathophysiology of fragile X (and what it teaches us about synapses).
AB  - Fragile X is the most common known inherited cause of intellectual disability and
      autism, and it typically results from transcriptional silencing of FMR1 and loss
      of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an
      mRNA-binding protein that functions at many synapses to inhibit local translation
      stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies
      on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have
      yielded deeper insight into how synaptic protein synthesis and plasticity are
      regulated by experience. This new knowledge has also suggested ways that altered
      signaling and synaptic function can be corrected in fragile X, and human clinical
      trials based on this information are under way.

PMID- 22483048
TI  - Relationships between in vivo and in vitro aflatoxin production: reliable
      prediction of fungal ability to contaminate maize with aflatoxins.
AB  - Aflatoxins are highly carcinogenic mycotoxins frequently produced by Aspergillus
      flavus. Contamination of maize with aflatoxins imposes both economic and health
      burdens in many regions. Identification of the most important etiologic agents of
      contamination is complicated by mixed infections and varying aflatoxin-producing
      potential of fungal species and individuals. In order to know the potential
      importance of an isolate to cause a contamination event, the ability of the
      isolate to produce aflatoxins on the living host must be determined. Aflatoxin
      production in vitro (synthetic and natural media) was contrasted with in vivo
      (viable maize kernels) in order to determine ability of in vitro techniques to
      predict the relative importance of causal agents to maize contamination events.
      Several media types and fermentation techniques (aerated, non-aerated,
      fermentation volume) were compared. There was no correlation between aflatoxin
      production in viable maize and production in any of the tested liquid
      fermentation media using any of the fermentation techniques. Isolates that
      produced aflatoxins on viable maize frequently failed to produce detectable
      (limit of detection=1ppb) aflatoxin concentrations in synthetic media. Aflatoxin
      production on autoclaved maize kernels was highly correlated with production on
      viable maize kernels. The results have important implications for researchers
      seeking to either identify causal agents of contamination events or characterize
      atoxigenic isolates for biological control.

PMID- 22483049
TI  - Evaluation of the potential for sexual reproduction in field populations of
      Cercospora beticola from USA.
AB  - Cercospora leaf spot, caused by the hemibiotrophic fungal pathogen Cercospora
      beticola, is the most economically damaging foliar disease of sugarbeet
      worldwide. Although most C. beticola populations display characteristics
      reminiscent of sexual recombination, no teleomorph has been described. To assess
      whether populations in northern United States have characteristics consistent
      with sexual reproduction, 1024 isolates collected over a 3-y period were analyzed
      for frequency and distribution of mating type genes. After clone correction, an
      approximately equal distribution of mating types was found for each sampling
      year. Mating type frequency was also assessed in individual lesions. Lesions
      always consisted of isolates with a single mating type and microsatellite
      haplotype, but both mating types and up to five microsatellite haplotypes could
      be found on an individual leaf. The MAT1-1-1 and MAT1-2-1 genes were sequenced
      from 28 MAT1-1 and 28 MAT1-2 isolates, respectively. Three MAT1-1-1 nucleotide
      haplotypes were identified that encoded a single amino acid sequence. For MAT1-2
      1, five nucleotide haplotypes were identified that encoded four protein variants.
      MAT1-1-1 and MAT1-2-1 gene expression analyses were conducted on plants
      inoculated with either or both mating types. MAT1-1-1 expression remained low,
      but MAT1-2-1 spiked during late stages of colonization. A segment of the MAT1-2-1
      coding sequence was also found in MAT1-1 isolates. Taken together, these results
      suggest that C. beticola has the potential for sexual reproduction.

PMID- 22483050
TI  - Discovery of multiple IGS haplotypes within genotypes of Puccinia striiformis.
AB  - In a search for specific molecular markers for population analysis of Puccinia
      striiformis f. sp. tritici, the ribosomal DNA (rDNA) intergenic spacer (IGS) 1
      region (rDNA-IGS1, between the 28S and the 5S rDNA genes) was amplified, cloned,
      and sequenced. It was found to exhibit multiple bands and length polymorphism.
      Surprisingly, single isolates were found to possess between three to five
      different IGS1 haplotypes. Bands were cloned and sequenced, and two highly
      variable regions (alpha and beta) were found between conserved regions, with
      repeat units interspersed in both types of regions. There were 14 different
      repeat units, and these were sometimes grouped further into four combinations of
      repeat units, with a few individual nucleotides (A or C) inserted between the
      repeats. Among three geographically dispersed isolates, the variable region alpha
      was divided into eight types, and the variable region beta was divided into two
      types based on repeat units. Most of the 14 repeat units were shared by the
      variable and the conserved regions. Among the three isolates, there were a total
      of 12 IGS1 haplotypes, but some of these were shared between isolates such that
      there were only eight unique haplotypes. The occurrence of multiple haplotypes
      within single isolates may be useful for analyzing the population structure,
      tracking the origin of annual epidemics and providing insights into evolutionary
      biology of this pathogen.

PMID- 22483051
TI  - The cellulose synthase 3 (CesA3) gene of oomycetes: structure, phylogeny and
      influence on sensitivity to carboxylic acid amide (CAA) fungicides.
AB  - Proper disease control is very important to minimize yield losses caused by
      oomycetes in many crops. Today, oomycete control is partially achieved by
      breeding for resistance, but mainly by application of single-site mode of action
      fungicides including the carboxylic acid amides (CAAs). Despite having mostly
      specific targets, fungicidal activity can differ even in species belonging to the
      same phylum but the underlying mechanisms are often poorly understood. In an
      attempt to elucidate the phylogenetic basis and underlying molecular mechanism of
      sensitivity and tolerance to CAAs, the cellulose synthase 3 (CesA3) gene was
      isolated and characterized, encoding the target site of this fungicide class. The
      CesA3 gene was present in all 25 species included in this study representing the
      orders Albuginales, Leptomitales, Peronosporales, Pythiales, Rhipidiales and
      Saprolegniales, and based on phylogenetic analyses, enabled good resolution of
      all the different taxonomic orders. Sensitivity assays using the CAA fungicide
      mandipropamid (MPD) demonstrated that only species belonging to the
      Peronosporales were inhibited by the fungicide. Molecular data provided evidence,
      that the observed difference in sensitivity to CAAs between Peronosporales and
      CAA tolerant species is most likely caused by an inherent amino acid
      configuration at position 1109 in CesA3 possibly affecting fungicide binding. The
      present study not only succeeded in linking CAA sensitivity of various oomycetes
      to the inherent CesA3 target site configuration, but could also relate it to the
      broader phylogenetic context.

PMID- 22483052
TI  - Fungi associated with the southern Eurasian orchid Spiranthes spiralis (L.)
      Chevall.
AB  - The hitherto unknown relationships between the European orchid Spiranthes
      spiralis (L.) Chevall and its internally associated fungi were explored by a
      combined approach involving microscopy-based investigations at a morpho
      histological level as well as by molecular analyses of the identity of the
      eukaryotic endophytes present in the root tissue of the plant. We found that this
      orchid which is currently reported to have a vulnerable status in northern Italy,
      can host and interact with at least nine types of fungi. Some of these fungi show
      similarity to mycorrhizal genera found in orchids such as the Ceratobasidium
      Rhizoctonia group. Other fungi found are from the genera Davidiella (Ascomycota),
      Leptosphaeria (Ascomycota), Alternaria (Ascomycota), and Malassezia
      (Basidiomycota), some of which until have not previously been reported to have an
      endophytic relationship with plants. The repeated occurrence of often pathogenic
      fungi such as Fusarium oxysporum, Bionectria ochroleuca, and Alternaria sp.,
      within healthy specimens of this orchid suggests a tempered interaction with
      species that are sometimes deleterious to non-orchid plants. The fact is
      reminiscent of the symbiotic compromise established by orchids with fungi of the
      rhizoctonia group.

PMID- 22483053
TI  - A hybrid deformable model for real-time surgical simulation.
AB  - Modeling organ deformation in real remains a challenge in virtual minimally
      invasive (MIS) surgery simulation. In this paper, we propose a new hybrid
      deformable model to simulate deformable organs in the real-time surgical training
      system. Our hybrid model uses boundary element method (BEM) to compute global
      deformation based on a coarse surface mesh and uses a mass-spring model to
      simulate the dynamic behaviors of soft tissue interacting with surgical
      instruments. The simulation result is coupled with a high-resolution rendering
      mesh through a particle surface interpolation algorithm. Accurate visual and
      haptic feedbacks are provided in real time and temporal behaviors of biological
      soft tissues including viscosity and creeping are modeled as well. We prove our
      model to be suitable to work in complex virtual surgical environment by
      integrating it into a MIS training system. The hybrid model is evaluated with
      respect to efficiency, accuracy and robustness by a series of experiments.

PMID- 22483054
TI  - A minimally invasive multimodality image-guided (MIMIG) system for peripheral
      lung cancer intervention and diagnosis.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related death in the
      United States, with more than half of the cancers are located peripherally.
      Computed tomography (CT) has been utilized in the last decade to detect early
      peripheral lung cancer. However, due to the high false diagnosis rate of CT,
      further biopsy is often necessary to confirm cancerous cases. This renders
      intervention for peripheral lung nodules (especially for small peripheral lung
      cancer) difficult and time-consuming, and it is highly desirable to develop new,
      on-the-spot earlier lung cancer diagnosis and treatment strategies. PURPOSE: The
      objective of this study is to develop a minimally invasive multimodality image
      guided (MIMIG) intervention system to detect lesions, confirm small peripheral
      lung cancer, and potentially guide on-the-spot treatment at an early stage.
      Accurate image guidance and real-time optical imaging of nodules are thus the key
      techniques to be explored in this work. METHODS: The MIMIG system uses CT images
      and electromagnetic (EM) tracking to help interventional radiologists target the
      lesion efficiently. After targeting the lesion, a fiber-optic probe coupled with
      optical molecular imaging contrast agents is used to confirm the existence of
      cancerous tissues on-site at microscopic resolution. Using the software
      developed, pulmonary vessels, airways, and nodules can be segmented and
      visualized for surgical planning; the segmented results are then transformed onto
      the intra-procedural CT for interventional guidance using EM tracking.
      Endomicroscopy through a fiber-optic probe is then performed to visualize tumor
      tissues. Experiments using IntegriSense 680 fluorescent contrast agent labeling
      alphavbeta3 integrin were carried out for rabbit lung cancer models. Confirmed
      cancers could then be treated on-the-spot using radio-frequency ablation (RFA).
      RESULTS: The prototype system is evaluated using the rabbit VX2 lung cancer model
      to evaluate the targeting accuracy, guidance efficiency, and performance of
      molecular imaging. Using this system, we achieved an average targeting accuracy
      of 3.04 mm, and the IntegriSense signals within the VX2 tumors were found to be
      at least two-fold higher than those of normal tissues. The results demonstrate
      great potential for applying the system in human trials in the future if an
      optical molecular imaging agent is approved by the Food and Drug Administration
      (FDA). CONCLUSIONS: The MIMIG system was developed for on-the-spot interventional
      diagnosis of peripheral lung tumors by combining image-guidance and molecular
      imaging. The system can be potentially applied to human trials on diagnosing and
      treating earlier stage lung cancer. For current clinical applications, where a
      biopsy is unavoidable, the MIMIG system without contrast agents could be used for
      biopsy guidance to improve the accuracy and efficiency.

PMID- 22483055
TI  - Biomechanical characterisation of ovine spinal facet joint cartilage.
AB  - The spinal facet joints are known to be an important component in the kinematics
      and the load transmission of the spine. The articular cartilage in the facet
      joint is prone to degenerative changes which lead to back pain and treatments for
      the condition have had limited long term success. There is currently a lack of
      information on the basic biomechanical properties of the facet joint cartilage
      which is needed to develop tissue substitution or regenerative interventions. In
      the present study, the thickness and biphasic properties of ovine facet cartilage
      were determined using a combination of indentation tests and computational
      modelling. The equilibrium biphasic Young's modulus and permeability were derived
      to be 0.76+/-0.35 MPa and 1.61+/-1.10*10-15 m4/(Ns) respectively, which were
      within the range of cartilage properties characterised from the human synovial
      joints. The average thickness of the ovine facet cartilage was 0.52+/-0.10 mm,
      which was measured using a needle indentation test. These properties could
      potentially be used for the development of substitution or tissue engineering
      interventions and for computational modelling of the facet joint. Furthermore,
      the developed method to characterise the facet cartilage could be used for other
      animals or human donors.

PMID- 22483056
TI  - The association of tooth scaling and decreased cardiovascular disease: a
      nationwide population-based study.
AB  - OBJECTIVE: Poor oral hygiene has been associated with an increased risk for
      cardiovascular disease. However, the association between preventive dentistry and
      cardiovascular risk reduction has remained undetermined. The aim of this study is
      to investigate the association between tooth scaling and the risk of
      cardiovascular events by using a nationwide, population-based study and a
      prospective cohort design. METHODS: Our analyses were conducted using information
      from a random sample of 1 million persons enrolled in the nationally
      representative Taiwan National Health Insurance Research Database. Exposed
      individuals consisted of all subjects who were aged >= 50 years and who received
      at least 1 tooth scaling in 2000. The comparison group of non-exposed persons
      consisted of persons who did not undergo tooth scaling and were matched to
      exposed individuals using propensity score matching by the time of enrollment,
      age, gender, history of coronary artery disease, diabetes, hypertension, and
      hyperlipidemia. RESULTS: During an average follow-up period of 7 years, 10,887
      subjects who had ever received tooth scaling (exposed group) and 10,989 age-,
      gender-, and comorbidity-matched subjects who had not received tooth scaling (non
      exposed group) were enrolled. The exposed group had a lower incidence of acute
      myocardial infarction (1.6% vs 2.2%, P<.001), stroke (8.9% vs 10%, P=.03), and
      total cardiovascular events (10% vs 11.6%, P<.001) when compared with the non
      exposed group. After multivariate analysis, tooth scaling was an independent
      factor associated with less risk of developing future myocardial infarction
      (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.57-0.85), stroke (HR,
      0.85; 95% CI, 0.78-0.93), and total cardiovascular events (HR, 0.84; 95% CI, 0.77
      0.91). Furthermore, when compared with the non-exposed group, increasing
      frequency of tooth scaling correlated with a higher risk reduction of acute
      myocardial infarction, stroke, and total cardiovascular events (P for
      trend<.001). CONCLUSION: Tooth scaling was associated with a decreased risk for
      future cardiovascular events.

PMID- 22483057
TI  - Why P is not perfect.

PMID- 22483058
TI  - Acute cytomegalovirus colitis mimicking exacerbation of ulcerative colitis:
      precipitating or coincidental?

PMID- 22483059
TI  - Patient-centered shared decision-making: a public imperative.

PMID- 22483060
TI  - Lead poisoning mimicking amyotrophic lateral sclerosis: an adverse effect of
      rituals.

PMID- 22483061
TI  - A childlike presentation?

PMID- 22483062
TI  - [Explanation of samples sizes in current biomedical journals: an irrational
      requirement].
AB  - OBJECTIVES: To discuss the theoretical relevance of current requirements for
      explanations of the sample sizes employed in published studies, and to assess the
      extent to which these requirements are currently met by authors and demanded by
      referees and editors. METHODS: A literature review was conducted to gain insight
      into and critically discuss the possible rationale underlying the requirement of
      justifying sample sizes. A descriptive bibliometric study was then carried out
      based on the original studies published in the six journals with the highest
      impact factor in the field of health in 2009. RESULTS: All the arguments used to
      support the requirement of an explanation of sample sizes are feeble, and there
      are several reasons why they should not be endorsed. These instructions are
      neglected in most of the studies published in the current literature with the
      highest impact factor. In 56% (95%CI: 52-59) of the articles, the sample size
      used was not substantiated, and only 27% (95%CI: 23-30) met all the requirements
      contained in the guidelines adhered to by the journals studied. CONCLUSIONS:
      Based on this study, we conclude that there are no convincing arguments
      justifying the requirement for an explanation of how the sample size was reached
      in published articles. There is no sound basis for this requirement, which not
      only does not promote the transparency of research reports but rather contributes
      to undermining it.

PMID- 22483063
TI  - Di- and tetra-nuclear copper(II), nickel(II), and cobalt(II) complexes of four
      bis-tetradentate triazole-based ligands: synthesis, structure, and magnetic
      properties.
AB  - Four bis-tetradentate N(4)-substituted-3,5-{bis[bis-N-(2
      pyridinemethyl)]aminomethyl}-4H-1,2,4-triazole ligands, L(Tz1)-L(Tz4), differing
      only in the triazole N(4) substituent R (where R is amino, pyrrolyl, phenyl, or 4
      tertbutylphenyl, respectively) have been synthesized, characterized, and reacted
      with M(II)(BF(4))(2).6H(2)O (M(II) = Cu, Ni or Co) and Co(SCN)(2). Experiments
      using all 16 possible combinations of metal salt and L(TzR) were carried out: 14
      pure complexes were obtained, 11 of which are dinuclear, while the other three
      are tetranuclear. The dinuclear complexes include two copper(II) complexes,
      [Cu(II)(2)(L(Tz2))(H(2)O)(4)](BF(4))(4) (2),
      [Cu(II)(2)(L(Tz4))(BF(4))(2)](BF(4))(2) (4); two nickel(II) complexes,
      [Ni(II)(2)(L(Tz1))(H(2)O)(3)(CH(3)CN)](BF(4))(4).0.5(CH(3)CN) (5) and
      [Ni(II)(2)(L(Tz4))(H(2)O)(4)](BF(4))(4).H(2)O (8); and seven cobalt(II)
      complexes, [Co(II)(2)(L(Tz1))(MU-BF(4))](BF(4))(3).H(2)O (9),
      [Co(II)(2)(L(Tz2))(MU-BF(4))](BF(4))(3).2H(2)O (10),
      [Co(II)(2)(L(Tz3))(H(2)O)(2)](BF(4))(4) (11), [Co(II)(2)(L(Tz4))(MU
      BF(4))](BF(4))(3).3H(2)O (12), [Co(II)(2)(L(Tz1))(SCN)(4)].3H(2)O (13),
      [Co(II)(2)(L(Tz2))(SCN)(4)].2H(2)O (14), and [Co(II)(2)(L(Tz3))(SCN)(4)].H(2)O
      (15). The tetranuclear complexes are
      [Cu(II)(4)(L(Tz1))(2)(H(2)O)(2)(BF(4))(2)](BF(4))(6) (1),
      [Cu(II)(4)(L(Tz3))(2)(H(2)O)(2)(MU-F)(2)](BF(4))(6).0.5H(2)O (3), and
      [Ni(II)(4)(L(Tz3))(2)(H(2)O)(4)(MU-F(2))](BF(4))(6).6.5H(2)O (7). Single crystal
      X-ray structure determinations revealed different solvent content from that found
      by microanalysis of the bulk sample after drying under a vacuum and confirmed
      that 5', 8', 9', 11', 12', and 15' are dinuclear while 1' and 7' are
      tetranuclear. As expected, magnetic measurements showed that weak
      antiferromagnetic intracomplex interactions are present in 1, 2, 4, 7, and 8,
      stabilizing a singlet spin ground state. All seven of the dinuclear cobalt(II)
      complexes, 9-15, have similar magnetic behavior and remain in the [HS-HS] state
      between 300 and 1.8 K.

PMID- 22483064
TI  - Salidroside protects human erythrocytes against hydrogen peroxide-induced
      apoptosis.
AB  - Rhodiola rosea is a commonly used folk medicine for the treatment of high
      altitude sickness, mountain malhypoxia, and anoxia. Its active ingredient,
      salidroside [2-(4-hydroxyphenyl)ethyl beta-D-glucopyranoside (1)], has been
      reported to have a broad spectrum of biological effects. However, the protective
      role of 1 in human erythrocytes remains unclear. This study therefore has
      investigated the effects of 1 on oxidative stress-induced apoptosis in human
      erythrocytes (also known as eryptosis or erythroptosis). Compound 1 increased
      cell survival significantly and prevented human erythrocytes from undergoing
      eryptosis/erythroptosis mediated by H(2)O(2), as confirmed by the decreased
      expression of phosphatidylserine on the cell surface and reduced leakage of
      calcein through the damaged membrane. Mechanistically, 1 was found to exert its
      protective effects through its antioxidative activity and the inhibition of
      caspase-3 activation and stress-induced intracellular Ca(2+) rise in a dose
      dependent manner. Compound 1 is a protective agent in human erythrocytes against
      oxidative stress and may be a good adaptogen to enhance the body's resistance to
      stress and fatigue.

PMID- 22483065
TI  - Olefin isomerization regiochemistries during tandem action of BacA and BacB on
      prephenate in bacilysin biosynthesis.
AB  - BacA and BacB, the first two enzymes of the bacilysin pathway, convert prephenate
      to an exocylic regioisomer of dihydrohydroxyphenylpyruvate (ex-H(2)HPP) on the
      way to the epoxycyclohexanone warhead in the dipeptide antibiotic, bacilysin.
      BacA decarboxylates prephenate without aromatization, converting the 1,4-diene in
      prephenate to the endocyclic 1,3-diene in Delta(4),Delta(8)
      dihydrohydroxyphenylpyruvate (en-H(2)HPP). BacB then performs an allylic
      isomerization to bring the diene into conjugation with the 2-ketone in the
      product Delta(3),Delta(5)-dihydrohydroxyphenylpyruvate (ex-H(2)HPP). To prove
      that BacA acts regiospecifically on one of the two prochiral olefins in
      prephenate, we generated 1,5,8-[(13)C]-chorismate from bacterial fermentation of
      5-[(13)C]-glucose and in turn produced 2,4,6-[(13)C]-prephenate via chorismate
      mutase. Tandem action of BacA and BacB gave 2,4,8-[(13)C]-7R-ex-H(2)HPP, showing
      that BacA isomerizes only the pro-R double bond in prephenate. Nonenzymatic
      isomerization of the BacA product into conjugation gives only the Delta(3)E
      geometric isomer of Delta(3),Delta(5)-ex-H(2)HPP. On the other hand, acceleration
      of the allylic isomerization by BacB gives a mixture of the E- and Z-geometric
      isomers of the 7R- product, indicating some rerouting of the flux, likely through
      dienolate geometric isomers.

PMID- 22483066
TI  - Long term follow-up of Polycythemia Vera patients treated with imatinib mesylate.

PMID- 22483067
TI  - Progressive arterial occlusive disease (PAOD) and pulmonary arterial hypertension
      (PAH) as new adverse events of second generation TKIs in CML treatment: who's
      afraid of the big bad wolf?

PMID- 22483068
TI  - Neutrophilic panniculitis following azacitidine treatment for myelodysplastic
      syndromes.

PMID- 22483069
TI  - Acute myeloid leukemia with minimal differentiation: unusual cytogenetics,
      morphology, phenotype and clinical course.

PMID- 22483071
TI  - Comment on "The physiology of developmental changes in BOLD functional imaging
      signals" by Harris, Reynell, and Attwell.

PMID- 22483070
TI  - Facing changes and changing faces in adolescence: a new model for investigating
      adolescent-specific interactions between pubertal, brain and behavioral
      development.
AB  - Adolescence is a time of dramatic physical, cognitive, emotional, and social
      changes as well as a time for the development of many social-emotional problems.
      These characteristics raise compelling questions about accompanying neural
      changes that are unique to this period of development. Here, we propose that
      studying adolescent-specific changes in face processing and its underlying neural
      circuitry provides an ideal model for addressing these questions. We also use
      this model to formulate new hypotheses. Specifically, pubertal hormones are
      likely to increase motivation to master new peer-oriented developmental tasks,
      which will in turn, instigate the emergence of new social/affective components of
      face processing. We also predict that pubertal hormones have a fundamental impact
      on the re-organization of neural circuitry supporting face processing and
      propose, in particular, that, the functional connectivity, or temporal synchrony,
      between regions of the face-processing network will change with the emergence of
      these new components of face processing in adolescence. Finally, we show how this
      approach will help reveal why adolescence may be a period of vulnerability in
      brain development and suggest how it could lead to prevention and intervention
      strategies that facilitate more adaptive functional interactions between regions
      within the broader social information processing network.

PMID- 22483072
TI  - ERP correlates of unexpected word forms in a picture-word study of infants and
      adults.
AB  - We tested 14-month-olds and adults in an event-related potentials (ERPs) study in
      which pictures of familiar objects generated expectations about upcoming word
      forms. Expected word forms labelled the picture (word condition), while
      unexpected word forms mismatched by either a small deviation in word medial vowel
      height (mispronunciation condition) or a large deviation from the onset of the
      first speech segment (pseudoword condition). Both infants and adults showed
      sensitivity to both types of unexpected word form. Adults showed a chain of
      discrete effects: positivity over the N(1) wave, negativity over the P(2) wave
      (PMN effect) and negativity over the N(2) wave (N400 effect). Infants showed a
      similar pattern, including a robust effect similar to the adult P(2) effect.
      These observations were underpinned by a novel visualisation method which shows
      the dynamics of the ERP within bands of the scalp over time. The results
      demonstrate shared processing mechanisms across development, as even subtle
      deviations from expected word forms were indexed in both age groups by a
      reduction in the amplitude of characteristic waves in the early auditory evoked
      potential.

PMID- 22483073
TI  - Measures of frontal functioning and the emergence of inhibitory control processes
      at 10 months of age.
AB  - During the first year, infants begin to exhibit initial evidence of working
      memory and inhibitory control in conjunction with substantial maturation of the
      frontal cortex and corresponding neural circuitry. Currently, relatively little
      is known about the neural and autonomic resources that are recruited in response
      to increased executive demands during the first year of development. To this end,
      we recorded electroencephalogram (EEG; 6-9 Hz) and electrocardiogram from 10
      month-olds during a working memory and inhibitory control task (looking A-not-B).
      Analyses compared measures of frontal functioning (EEG power, EEG coherence,
      heart rate) during nonreversal (working memory) and reversal (working
      memory+inhibitory control) trials. The increased cognitive demand of inhibitory
      control processing was associated with increases in heart rate and frontal
      coherence (medial frontal-lateral frontal, medial frontal-temporal, medial
      frontal-medial parietal, and medial frontal-occipital electrode pairs). Thus,
      synchronized activity across distributed cortical regions appeared to be
      essential to inhibitory control processes during infancy. The addition of
      inhibitory control processes, however, was not associated with any changes in
      neuronal activity (EEG power). These findings are discussed in relation to other
      neuroscience findings and provide insight into the development of integrated
      frontal functioning in infancy.

PMID- 22483074
TI  - Processing of novel and familiar faces in infants at average and high risk for
      autism.
AB  - The study investigated whether infant siblings of children with autism (sibs-ASD)
      process familiar and novel faces differently from typical infants and whether
      sensitivity to face familiarity is associated with infants' social and
      communicative behaviors. Visual event-related potentials (ERPs) were recorded in
      35 infants, age 9 months +/- 15 days (20 typical infants, 15 sibs-ASD) using an
      oddball paradigm presenting photographs of infants' mothers (70% of trials) and
      an unfamiliar female (30% of trials). Eye tracking responses to a different
      unfamiliar face were recorded to determine whether differences in gaze patterns
      might account for any ERP differences found. There were no group differences in
      the distribution, number or duration of fixations. Both infant groups
      differentiated between mothers and strangers, as reflected in amplitude
      modulations of posterior N290/P400 and frontal/central Nc responses. Group
      differences were present in the latency of the P400 response, where a delayed
      response to the stranger face was observed only in typical infants. Across both
      groups, shorter Nc latency to mother's face was associated with parental reports
      of stronger interpersonal skills. Individual differences in the speed of
      processing for novel vs. familiar faces may be an informative early marker of
      risk for atypical social development.

PMID- 22483076
TI  - Isolating N400 as neural marker of vocal anger processing in 6-11-year old
      children.
AB  - INTRODUCTION: Vocal anger is a salient social signal serving adaptive functions
      in typical child development. Despite recent advances in the developmental
      neuroscience of emotion processing with regard to visual stimuli, little remains
      known about the neural correlates of vocal anger processing in childhood. This
      study represents the first attempt to isolate a neural marker of vocal anger
      processing in children using electrophysiological methods. METHODS: We compared
      ERP wave forms during the processing of non-word emotional vocal stimuli in a
      population sample of 55 6-11-year-old typically developing children. Children
      listened to three types of stimuli expressing angry, happy, and neutral prosody
      and completed an emotion identification task with three response options (angry,
      happy and neutral/'ok'). RESULTS: A distinctive N400 component which was
      modulated by emotional content of vocal stimulus was observed in children over
      parietal and occipital scalp regions-amplitudes were significantly attenuated to
      angry compared to happy and neutral voices. DISCUSSION: Findings of the present
      study regarding the N400 are compatible with adult studies showing reduced N400
      amplitudes to negative compared to neutral emotional stimuli. Implications for
      studies of the neural basis of vocal anger processing in children are discussed.

PMID- 22483075
TI  - Anomalous functional brain activation following negative mood induction in
      children with pre-school onset major depression.
AB  - While major depressive disorder has been shown to be a significant mental health
      issue for school-age children, recent research indicates that depression can be
      observed in children as early as the preschool period. Yet, little work has been
      done to explore the neurobiological factors associated with this early form of
      depression. Given research suggesting a relation between adult depression and
      anomalies in emotion-related neural circuitry, the goal of the current study was
      to elucidate changes in functional activation during negative mood induction and
      emotion regulation in school-age children with a history of preschool-onset
      depression. The results suggest that a history of depression during the preschool
      period is associated with decreased activity in prefrontal cortex during mood
      induction and regulation. Moreover, the severity of current depressed mood was
      associated with increased activity in limbic regions, such as the amygdala,
      particularly in children with a history of depression. Similar to results
      observed in adult depression, the current findings indicate disruptions in
      emotion-related neural circuitry associated with preschool-onset depression.

PMID- 22483077
TI  - Comparing the neural bases of self-referential processing in typically developing
      and 22q11.2 adolescents.
AB  - The investigation of self-reflective processing during adolescence is relevant,
      as this period is characterized by deep reorganization of the self-concept. It
      may be the case that an atypical development of brain regions underlying self
      reflective processing increases the risk for psychological disorders and impaired
      social functioning. In this study, we investigated the neural bases of self- and
      other-related processing in typically developing adolescents and youths with
      22q11.2 deletion syndrome (22q11DS), a rare neurogenetic condition associated
      with difficulties in social interactions and increased risk for schizophrenia.
      The fMRI paradigm consisted in judging if a series of adjectives applied to the
      participant himself/herself (self), to his/her best friend or to a fictional
      character (Harry Potter). In control adolescents, we observed that self- and
      other-related processing elicited strong activation in cortical midline
      structures (CMS) when contrasted with a semantic baseline condition. 22q11DS
      exhibited hypoactivation in the CMS and the striatum during the processing of
      self-related information when compared to the control group. Finally, the
      hypoactivation in the anterior cingulate cortex was associated with the severity
      of prodromal positive symptoms of schizophrenia. The findings are discussed in a
      developmental framework and in light of their implication for the development of
      schizophrenia in this at-risk population.

PMID- 22483078
TI  - Size, structure, and helical twist of graphene nanoribbons controlled by
      confinement in carbon nanotubes.
AB  - Carbon nanotubes (CNTs) act as efficient nanoreactors, templating the assembly of
      sulfur-terminated graphene nanoribbons (S-GNRs) with different sizes, structures,
      and conformations. Spontaneous formation of nanoribbons from small sulfur
      containing molecules is efficiently triggered by heat treatment or by an 80 keV
      electron beam. S-GNRs form readily in CNTs with internal diameters between 1 and
      2 nm. Outside of this optimum range, nanotubes narrower than 1 nm do not have
      sufficient space to accommodate the 2D structure of S-GNRs, while nanotubes wider
      than 2 nm do not provide efficient confinement for unidirectional S-GNR growth,
      thus neither can support nanoribbon formation. Theoretical calculations show that
      the thermodynamic stability of nanoribbons is dependent on the S-GNR edge
      structure and, to a lesser extent, the width of the nanoribbon. For nanoribbons
      of similar widths, the polythiaperipolycene-type edges of zigzag S-GNRs are more
      stable than the polythiophene-type edges of armchair S-GNRs. Both the edge
      structure and the width define the electronic properties of S-GNRs which can vary
      widely from metallic to semiconductor to insulator. The encapsulated S-GNRs
      exhibit diverse dynamic behavior, including rotation, translation, and helical
      twisting inside the nanotube, which offers a mechanism for control of the
      electronic properties of the graphene nanoribbon via confinement at the
      nanoscale.

PMID- 22483079
TI  - Improving inpatient pediatric healthcare quality, education and research: the
      past, present, and inspired future of pediatric hospital medicine. Foreword.

PMID- 22483080
TI  - Pediatric hospital medicine: historical perspectives, inspired future.
AB  - Pediatric hospital medicine (PHM) is in an accelerated growth phase. Multiple
      elements have combined to affect the current state of the field. PHM is similar
      to other geographic specialties such as pediatric emergency medicine and
      pediatric critical care that deliver general, comprehensive care to patients
      based on hospital site. Pediatric hospitalists have been molded by changes in
      medicine, consumer expectations, and training program modifications. The history
      of PHM dates back for more than 3 decades, when unwitting pediatricians began to
      focus on delivering care for the hospitalized child. The ensuing years allowed
      for natural responses to external pressures that resulted in much of the field's
      initial development. In more recent years, however, pediatric hospitalists have
      been catalysts for change and driving forces for health care systems'
      improvements. Simultaneous with this has been the nearly exponential surge of
      energy focused on targeted initiatives, which have further defined the field and
      brought attention on a national level. PHM is at a critical but brilliant
      juncture in development. Further decisions regarding scope and demonstration of
      competencies are important to make with clarity of purpose. Pediatric
      hospitalists are advancing child health in the inpatient setting through evidence
      based care, research, education, clinical excellence, advocacy, and health care
      business acumen. With a strong community sense and leadership evident, PHM has a
      bright future.

PMID- 22483081
TI  - Pediatric hospital medicine and children with medical complexity: past, present,
      and future.
AB  - Children with medical complexity, regardless of underlying diagnoses, share
      similar functional and resource use consequences, including: intensive service
      needs, reliance on technology, polypharmacy, and/or home care or congregate care
      to maintain a basic quality of life, high health resource utilization, and, an
      elevated need for care coordination. The emerging field of complex care is
      focused on the holistic medical care of these children, which requires both broad
      general pediatrics skills and specific expertise in care coordination and
      communication with patients, families, and other medical and non-medical care
      providers. Many pediatric hospitalists have developed an interest in care
      coordination for CMC, and pediatric hospitalists are in an ideal location to
      embrace complex care. As a result of these factors, complex care has emerged as a
      field with many pediatric hospitalists at the helm, in arenas ranging from
      clinical care of these patients, research into their care, and education of
      future providers. The objective of this section of the review article is to
      outline the past, present, and possible future of children with medical
      complexity within several arenas in the field of pediatric hospital medicine,
      including practice management, clinical care, research, education, and quality
      improvement.

PMID- 22483082
TI  - Pediatric hospitalists in medical education: current roles and future directions.
AB  - As the field of pediatric hospital medicine has evolved, pediatric hospitalists
      have become increasingly involved in medical student and resident education-
      providing direct education during clinical rotations, developing novel curricula
      to meet the demands of the new educational environment, occupying leadership
      roles in medical education, and more. The literature suggests that hospitalists
      possess the essential skills for teaching effectively, yet most hospitalists feel
      that additional training beyond residency is necessary to refine their knowledge
      and skills in education and in other essential domains. Several pediatric
      hospital medicine fellowships and continuing medical education activities have
      been developed in the last decade to meet this growing need. The recent
      publication of the Pediatric Hospital Medicine Core Competencies will help define
      the roles and expectations of practicing pediatric hospitalists, and will serve
      as a framework for future curriculum development in both graduate and continuing
      medical education.

PMID- 22483083
TI  - Research in pediatric hospital medicine: how research will impact clinical care.
AB  - Hospitalist medicine has enjoyed a period of rapid growth over the past 10 years
      and research within this domain is no exception. This article will describe the
      initial research conducted within the world of pediatric hospital medicine, what
      the future of research will hold and how this will impact the clinical practice
      of hospitalists who care for children. This is a review of pertinent literature
      that represents key progress within the emerging field of pediatric hospital
      medicine. Research within pediatric hospital medicine has progressed from initial
      studies defining the emerging field and single-center studies to widely expanding
      national research networks which aim to prioritize the research needs of the
      field and use data from multiple centers to enrich the body of evidence that
      guides clinical practice. The field of pediatric hospital medicine has grown
      rapidly over the past decade and has an exciting trajectory of ongoing growth and
      research.

PMID- 22483084
TI  - Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women
      at a gynecologic outpatient service.
AB  - OBJECTIVE: We sought to analyze the prevalence and clinical manifestations of
      Mycoplasma genitalium infection in a heterogeneous population of women. STUDY
      DESIGN: The study was designed as a cross-sectional case-control study. Women
      attending a gynecological outpatient service from 2003 through 2008 were invited
      to participate. RESULTS: The prevalence of M genitalium was 2.1% and of Chlamydia
      trachomatis was 2.8% among 5519 tested women. A total of 679 women were included.
      Both pelvic inflammatory disease (PID) and cervicitis were independently
      associated with M genitalium (odds ratio, 9.00; 95% confidence interval, 1.62
      49.89 and odds ratio, 3.80; 95% confidence interval, 2.06-7.03, respectively).
      Women with C trachomatis had a higher frequency of both PID (18.3% vs 4.9%, P <
      .001) and cervicitis (33.4% vs 22.3%, P < .001) than women with M genitalium.
      CONCLUSION: M genitalium was an independent and strong risk factor for both
      cervicitis and PID although, compared to C trachomatis, clinical manifestations
      were less frequent.

PMID- 22483085
TI  - Antenatal sexually transmitted infection screening in private and indigent
      clinics in a community hospital system.
AB  - OBJECTIVE: To determine whether clinics that serve indigent patients demonstrate
      equal compliance with sexually transmitted infection testing guidelines when
      compared with private clinics. STUDY DESIGN: One hundred eighty-three women were
      divided into cohorts based on whether they received prenatal care at a private or
      indigent clinic. Timing of required antenatal sexually transmitted infection
      screening was collected for 8 tests and compliance scores were calculated.
      Primary outcome was average compliance score compared between clinic types.
      Secondary outcomes included disease-specific compliance and percent of perfect
      compliance at different office types. RESULTS: Compliance was found to be
      different between clinic types (P = .023). Indigent clinics had the same median
      with slightly higher inner-quartile range than private clinics (7 [7-8], 7 [7
      7]). Indigent clinics had higher mean compliance scores (7.1 vs 6.9) and a
      greater percentage of patients demonstrating perfect compliance (42% vs 14%, P <
      .001). CONCLUSION: Clinics serving indigent patient populations had a higher
      compliance with required testing compared to private clinics. HIV testing in the
      third trimester remains the greatest need for improvement for all practice types.

PMID- 22483086
TI  - The professional responsibility model of physician leadership.
AB  - The challenges physician leaders confront today call to mind Odysseus' challenge
      to steer his fragile ship successfully between Scylla and Charybdis. The modern
      Scylla takes the form of ever-increasing pressures to provide more resources for
      professional liability, compliance, patient satisfaction, central administration,
      and a host of other demands. The modern Charybdis takes the form of ever
      increasing pressures to procure resources when fewer are available and
      competition is continuously increasing the need for resources, including managed
      care, hospital administration, payers, employers, patients who are uninsured or
      underinsured, research funding, and philanthropy. This publication provides
      physician leaders with guidance for identifying and managing common leadership
      challenges on the basis of the professional responsibility model of physician
      leadership. This model is based on Plato's concept of leadership as a life of
      service and the professional medical ethics of Drs John Gregory and Thomas
      Percival. Four professional virtues should guide physician leaders: self
      effacement, self-sacrifice, compassion, and integrity. These professional virtues
      direct physician leaders to treat colleagues as ends in themselves, to provide
      justice-based resource management, to use power constrained by medical
      professionalism, and to prevent and respond effectively to organizational
      dysfunction. The professional responsibility model guides physician leaders by
      proving an explicit "tool kit" to complement managerial skills.

PMID- 22483087
TI  - Perfectly packaged: upon delivery, the infant was still enclosed in the amniotic
      sac.

PMID- 22483088
TI  - Synthesis, cytotoxicity and apoptosis of cyclotriphosphazene compounds as anti
      cancer agents.
AB  - In the present study, a number of new dispirobino and dispiroansa spermine
      derivatives of cyclotriphosphazene (8-10, 13) were synthesized and characterized
      by elemental analysis, mass spectrometry, (1)H and (31)P NMR spectroscopy. At
      first, in vitro cytotoxic activity of cyclotriphosphazene compounds (1-14)
      against HT-29 (human colon adenocarcinoma), Hep2 (Human epidermoid larynx
      carcinoma), and Vero (African green monkey kidney) cell lines was investigated.
      Our study showed that most of these compounds stimulate apoptosis and they have
      cytotoxic effects for HT-29 and Hep2 cells. Additionally, these compounds (1-14)
      were investigated for their antibacterial activity against gram-positive
      (Staphylococcus aureus), gram-negative (Escherichia coli, Pseudomonas aeruginosa)
      bacteria and for their antifungal activity against Candida albicans, and were
      shown to be inactive.

PMID- 22483089
TI  - Design, synthesis and biological evaluation of thiazole- and indole-based
      derivatives for the treatment of type II diabetes.
AB  - Present studies have shown that the lipid carrier has a significant role in
      several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including
      type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives
      were synthesized and investigated for their inhibitory effects on the production
      of LPS-stimulated TNF-alpha. Among them, 12b exhibited an excellent inhibitory
      efficiency compared to BMS309403 (95% vs. 85%) at the concentration of 10 MUM and
      a binding affinity for ap2 with the apparent K(i) values 33 nM. Oral
      administration of 12b at a dosage of 50 mg/kg effectively reduced the levels of
      plasma blood glucose, triglycerides, insulin, total cholesterol and alanine
      aminotransferase in high-fat/diet-induced obesity model. The results highlighted
      that 12b was a potent anti-diabetic agent.

PMID- 22483090
TI  - The conversion of oridonin to spirolactone-type or enmein-type diterpenoid:
      synthesis and biological evaluation of ent-6,7-seco-oridonin derivatives as novel
      potential anticancer agents.
AB  - Starting from commercial available natural product oridonin (1), a practical
      synthesis of ent-6,7-seco-oridonin derivatives (2, 3, 5, and 9) was accomplished
      and their biological activities were evaluated. The conversion of spirolactone
      type diterpenoid to enmein-type was first completed. The results demonstrated
      that all synthesized ent-6,7-seco-oridonin derivatives could markedly inhibit the
      proliferation of cancer cells. Compared with Taxol, the most cytotoxic compound 5
      has similar potency in A549 cell and slightly less cytotoxicity in Bel-7402 cell.
      Compound 5 was also more potent than parent compound oridonin in mice with MGC
      803 gastric cancer in vivo. Then a series of novel 14-O-derivatives of 5 were
      further designed and synthesized, which showed better activity than 5 and similar
      activity as Taxol in vitro. The structure-activity relationships of oridonin
      derivatives were also discussed in the present investigations.

PMID- 22483091
TI  - Branching ratios for the reaction of selected carbonyl-containing peroxy radicals
      with hydroperoxy radicals.
AB  - An important chemical sink for organic peroxy radicals (RO(2)) in the troposphere
      is reaction with hydroperoxy radicals (HO(2)). Although this reaction is
      typically assumed to form hydroperoxides as the major products (R1a), acetyl
      peroxy radicals and acetonyl peroxy radicals have been shown to undergo other
      reactions (R1b) and (R1c) with substantial branching ratios: RO(2) + HO(2) ->
      ROOH + O(2) (R1a), RO(2) + HO(2) -> ROH + O(3) (R1b), RO(2) + HO(2) -> RO + OH +
      O(2) (R1c). Theoretical work suggests that reactions (R1b) and (R1c) may be a
      general feature of acyl peroxy and alpha-carbonyl peroxy radicals. In this work,
      branching ratios for R1a-R1c were derived for six carbonyl-containing peroxy
      radicals: C(2)H(5)C(O)O(2), C(3)H(7)C(O)O(2), CH(3)C(O)CH(2)O(2),
      CH(3)C(O)CH(O(2))CH(3), CH(2)ClCH(O(2))C(O)CH(3), and CH(2)ClC(CH(3))(O(2))CHO.
      Branching ratios for reactions of Cl-atoms with butanal, butanone, methacrolein,
      and methyl vinyl ketone were also measured as a part of this work. Product yields
      were determined using a combination of long path Fourier transform infrared
      spectroscopy, high performance liquid chromatography with fluorescence detection,
      gas chromatography with flame ionization detection, and gas chromatography-mass
      spectrometry. The following branching ratios were determined: C(2)H(5)C(O)O(2),
      Y(R1a) = 0.35 +/- 0.1, Y(R1b) = 0.25 +/- 0.1, and Y(R1c) = 0.4 +/- 0.1;
      C(3)H(7)C(O)O(2), Y(R1a) = 0.24 +/- 0.15, Y(R1b) = 0.29 +/- 0.1, and Y(R1c) =
      0.47 +/- 0.15; CH(3)C(O)CH(2)O(2), Y(R1a) = 0.75 +/- 0.13, Y(R1b) = 0, and Y(R1c)
      = 0.25 +/- 0.13; CH(3)C(O)CH(O(2))CH(3), Y(R1a) = 0.42 +/- 0.1, Y(R1b) = 0, and
      Y(R1c) = 0.58 +/- 0.1; CH(2)ClC(CH(3))(O(2))CHO, Y(R1a) = 0.2 +/- 0.2, Y(R1b) =
      0, and Y(R1c) = 0.8 +/- 0.2; and CH(2)ClCH(O(2))C(O)CH(3), Y(R1a) = 0.2 +/- 0.1,
      Y(R1b) = 0, and Y(R1c) = 0.8 +/- 0.2. The results give insights into possible
      mechanisms for cycling of OH radicals in the atmosphere.

PMID- 22483092
TI  - The role of vitamin D in pregnancy and lactation: insights from animal models and
      clinical studies.
AB  - Maternal adaptations during pregnancy and lactation appear to provide calcium to
      fetus and neonate without relying on vitamin D or calcitriol. Consequently, the
      blood calcium, calciotropic hormones, and skeleton appear normal at birth in the
      offspring of mothers who are severely vitamin D deficient or who lack calcitriol
      or its receptor. It remains unclear whether skeletal or extraskeletal problems
      will develop postnatally from exposure to vitamin D deficiency in utero. During
      the neonatal period, calcitriol-stimulated intestinal calcium absorption becomes
      the dominant mechanism of calcium delivery. The vitamin D-deficient neonate is at
      risk to develop hypocalcemia, rickets, and possibly extraskeletal disorders
      (e.g., type 1 diabetes). Breastfed babies are at higher risk of vitamin D
      deficiency because normally little vitamin D or 25-hydroxyvitamin D passes into
      breast milk. Dosing recommendations during pregnancy and lactation should ensure
      that the baby is born vitamin D sufficient and maintained that way during infancy
      and beyond.

PMID- 22483093
TI  - Editorial commentary: "All that glitters is not gold".

PMID- 22483095
TI  - Microwave-assisted extraction and dispersive liquid-liquid microextraction
      followed by gas chromatography-mass spectrometry for isolation and determination
      of polycyclic aromatic hydrocarbons in smoked fish.
AB  - A simple and efficient method was developed using microwave-assisted extraction
      (MAE) and dispersive liquid-liquid microextraction (DLLME) coupled with gas
      chromatography-mass spectrometry (GC-MS) for the extraction and quantification of
      16 polycyclic aromatic hydrocarbons (PAHs) in smoked fish. Benzo[a]pyrene,
      chrysene and pyrene were employed as model compounds and spiked to smoked fish to
      assess the extraction procedure. Several parameters, including the nature and
      volume of hydrolysis, extracting and disperser solvents, microwave time and pH,
      were optimized. In the optimum condition for MAE, 1g of fish sample was extracted
      in 12 mL KOH (2M) and ethanol with a 50:50 ratio in a closed-vessel system. For
      DLLME, 500 MUL of acetone (disperser solvent) containing 100 MUL of ethylene
      tetrachloride (extraction solvent) was rapidly injected by syringe into 12 mL of
      the sample extract solution (previously adjusted to pH 6.5), thereby forming a
      cloudy solution. Phase separation was performed by centrifugation and a volume of
      1.5 MUL of the sedimented phase was analyzed by GC-MS in select ion monitoring
      (SIM) mode. Satisfactory results were achieved when this method was applied to
      analyze the PAHs in smoked fish samples. The MAE-DLLME method coupled with GC-MS
      provided excellent enrichment factors (in the range of 244-373 for 16 PAHs) and
      good repeatability (with a relative standard deviation between 2.8 and 9%) for
      spiked smoked fish. The calibration graphs were linear in the range of 1-200 ng
      g(-1), with the square of the correlation coefficient (R(2))>0.981 and detection
      limits between 0.11 and 0.43 ng g(-1). The recoveries of those compounds in
      smoked fish were from 82.1% to 105.5%. A comparison of this method with previous
      methods demonstrated that the proposed method is an accurate, rapid and reliable
      sample-pretreatment method that gives very good enrichment factors and detection
      limits for extracting and determining PAHs from smoked fish.

PMID- 22483094
TI  - Interleukin-1 participates in the classical and alternative activation of
      microglia/macrophages after spinal cord injury.
AB  - BACKGROUND: Microglia and macrophages (MG/MPhi) have a diverse range of functions
      depending on unique cytokine stimuli, and contribute to neural cell death,
      repair, and remodeling during central nervous system diseases. While IL-1 has
      been shown to exacerbate inflammation, it has also been recognized to enhance
      neuroregeneration. We determined the activating phenotype of MG/MPhi and the
      impact of IL-1 in an in vivo spinal cord injury (SCI) model of IL-1 knock-out
      (KO) mice. Moreover, we demonstrated the contribution of IL-1 to both the
      classical and alternative activation of MG in vitro using an adult MG primary
      culture. METHODS: SCI was induced by transection of the spinal cord between the
      T9 and T10 vertebra in wild-type and IL-1 KO mice. Locomotor activity was
      monitored and lesion size was determined for 14 days. TNFalpha and Ym1 levels
      were monitored to determine the MG/MPhi activating phenotype. Primary cultures of
      MG were produced from adult mice, and were exposed to IFNgamma or IL-4 with and
      without IL-1beta. Moreover, cultures were exposed to IL-4 and/or IL-13 in the
      presence and absence of IL-1beta. RESULTS: The locomotor activity and lesion area
      of IL-1 KO mice improved significantly after SCI compared with wild-type mice.
      TNFalpha production was significantly suppressed in IL-1 KO mice. Also, Ym1, an
      alternative activating MG/MPhi marker, did not increase in IL-1 KO mice,
      suggesting that IL-1 contributes to both the classical and alternative activation
      of MG/MPhi. We treated primary MG cultures with IFNgamma or IL-4 in the presence
      and absence of IL-1beta. Increased nitric oxide and TNFalpha was present in the
      culture media and increased inducible NO synthase was detected in cell
      suspensions following co-treatment with IFNgamma and IL-1beta. Expression of the
      alternative activation markers Ym1 and arginase-1 was increased after exposure to
      IL-4 and further increased after co-treatment with IL-4 and IL-1beta. The
      phenotype was not observed after exposure of cells to IL-13. CONCLUSIONS: We
      demonstrate here in in vivo experiments that IL-1 suppressed SCI in a process
      mediated by the reduction of inflammatory responses. Moreover, we suggest that IL
      1 participates in both the classical and alternative activation of MG in in vivo
      and in vitro systems.

PMID- 22483096
TI  - Biocompatible phosphatidylcholine bilayer coated on magnetic nanoparticles and
      their application in the extraction of several polycyclic aromatic hydrocarbons
      from environmental water and milk samples.
AB  - In this work, phosphatidylcholine (PC) was coated on magnetic nanoparticles to
      form lipid bilayer as solid-phase extraction (SPE) sorbents for the enrichment of
      polycyclic aromatic hydrocarbons (PAHs) from environmental water and milk
      samples. The lipid bilayer was coated on Fe(3)O(4) nanoparticles using a modified
      dry lipid film hydration method. The resulted Fe(3)O(4)/PC could be readily
      isolated from solution with a magnet, and exhibited excellent adsorption
      performance to organic pollutants. Only 0.1g of sorbents was enough to extract
      PAHs from 500 mL aqueous solution, and 6 mL of acetonitrile was required to
      desorb them. The method was fast and relied on 10 min extraction time and 5 min
      magnetic separation. The proposed method was successfully applied to determine
      PAHs in some environmental water and milk samples. The detection limit was in the
      range of 0.2-0.6 ng L(-1). The recoveries of the spiked water samples ranged from
      89% to 115% with relative standard deviations (RSD) varying from 1% to 8%. For
      spiked milk samples, RSD was satisfactory (1-9%), but the recoveries were
      relatively low (42-62%). We show the potentials of Fe(3)O(4)/PC sorbents in
      environmental water and biological sample analyses.

PMID- 22483097
TI  - Bifunctional ultrasound assisted extraction and determination of Elettaria
      cardamomum Maton essential oil.
AB  - A new hyphenated extraction method composed of ultrasound assisted extraction
      (UAE)-optimized ultrasound assisted emulsification microextraction (USAEME) was
      developed for the extraction and preconcentration of the essential oil of
      Elettaria cardamomum Maton. The essential oil was analyzed by gas chromatography
      mass spectrometry (GC-MS) and optimization was performed using gas chromatography
      flame ionization detection (GC-FID). Ultrasound played two different roles in the
      extraction of the essential oil. First, as a source of sufficient energy to break
      the oil-containing glands in order to release the oil, and second as an
      emulsifier to disperse the organic phase within water. The effective parameters
      (factors) of USAEME including volume of extraction solvent (C(2)H(4)Cl(2)),
      extraction temperature and ultrasonic time were optimized by using a central
      composite design (CCD). The optimal conditions were 120 MUL for extraction
      solvent volume, 32.5  degrees C for temperature and 10.5 min for ultrasonic time.
      The linear dynamic ranges (LDRs) were 0.01-50 mg L(-1) with the determination
      coefficients in the range of 0.9990-0.9999. The limits of detection (LODs) and
      the relative standard deviations (RSDs) were 0.001-0.007 mg L(-1) and 3.6-6.3%,
      respectively. The enrichment factors were 93-98. The main components of the
      extracted essential oil were alpha-terpenyl acetate (46.0%), 1,8-cineole (27.7%),
      linalool (5.3%), alpha-terpineol (4.0%), linalyl acetate (3.5%).

PMID- 22483098
TI  - Myocardial strain of the left ventricle in normal children.
AB  - BACKGROUND: There have been few reports regarding cardiac strain in children. The
      present study was performed to determine the reference values for circumferential
      and radial strains of the left ventricle in normal children and discern the
      relative influence of aging and cardiac growth on these left ventricular
      functional indices. METHODS: The study population consisted of 180 children (aged
      2 months to 21 years) who had normal cardiac function and normal cardiac load.
      None of the patients had symptoms, and none was receiving medical therapy. 2D
      cine-loop recordings of short-axis views at the papillary muscle level were
      stored for off-line analysis. Custom acoustic-tracking software was used to
      measure left ventricular strain. Continuous variables are reported as mean values
      +/- standard deviation. The correlation coefficients were calculated to identify
      the relative influences of aging on the strains. Tukey's test was used to assess
      differences in strain among the six-myocardial segments. In all analyses, p<0.01
      was taken to indicate statistical significance. RESULTS AND CONCLUSIONS: The
      strains of all segments could be analyzed in 136 of 180 children. There were no
      significant age-related changes in circumferential or radial strain in children,
      but regional heterogeneity in left ventricular strain. The circumferential and
      radial strains showed inverse distributions; the circumferential strain in the
      region with low radial strain was high, and that in the region with high radial
      strain was low. These observations indicated there are differences among the
      three-dimensional movements of the regions.

PMID- 22483099
TI  - [Minimally invasive surgery learning: simulation training for OB GYN residents?].

PMID- 22483101
TI  - Human tripeptidyl peptidase II: a gentle giant.
AB  - Molecular structures can serve to either validate or rule out existing
      hypotheses, and they can also spawn new, deeper proposals about biochemical
      mechanism. In this issue of Structure, Schonegge et al. use single-particle cryo
      electron microscopy and flexible docking to examine the function of human
      tripeptidyl peptidase II, including the role of conformational changes in enzyme
      activation.

PMID- 22483100
TI  - Ambivalence about smoking and cue-elicited neural activity in quitting-motivated
      smokers faced with an opportunity to smoke.
AB  - Many cigarette smokers appear to experience ambivalence about smoking, defined as
      the simultaneous co-occurrence of a strong desire to smoke and a strong wish to
      quit smoking. Research suggests that this ambivalence about smoking affects how
      smokers respond to cigarette-related stimuli, but many important questions remain
      about precisely how smoking ambivalence influences cognitive and affective
      processing during cigarette cue exposure. We used functional magnetic resonance
      imaging (fMRI) to address this knowledge gap by examining the relation between
      self-reported ambivalence about smoking and cue-reactivity in quitting-motivated
      smokers presented with an opportunity to smoke. Eighty-two quitting-motivated
      cigarette smokers completed a measure assessing their ambivalence about smoking.
      Subsequently, participants initiated an attempt to quit smoking and underwent an
      fMRI session, during which they were asked to hold and view a cigarette.
      Consistent with hypotheses, results indicated that self-reported smoking
      ambivalence was negatively correlated with cigarette-related activation in brain
      areas linked to reward-related processing, motivation, and attention (i.e.,
      rostral anterior cingulate and medial prefrontal cortex, caudate nucleus, visual
      cortex). Self-reported ambivalence was not, however, correlated with activation
      in brain regions related to conflict processing. This pattern of results is
      discussed with respect to the process of change for those attempting to quit
      smoking.

PMID- 22483102
TI  - XPF-ERCC1: on the bubble.
AB  - In this issue of Structure, Das et al. report the structure of the helix-hairpin
      helix dimerization domain of XPF bound to ssDNA. These results provide insight
      into the architecture of nucleotide excision repair machinery and how it
      interacts with damaged DNA substrates.

PMID- 22483103
TI  - Discoidin discoveries.
AB  - In this issue of Structure, Carafoli et al. investigate the mode of antibody
      mediated inhibition of the discoidin domain receptor 1 (DDR1). These studies also
      provide new insight into activation of the DDRs, which are unique among receptor
      tyrosine kinases in the composition of their extracellular regions.

PMID- 22483104
TI  - Phosphorylation meets proteolysis.
AB  - Phosphorylation is a reversible post-translational modification that regulates
      many proteins and enzymes, including proteases, as shown by two recent
      publications. Huang and colleagues and Velazquez-Delgado and Hardy (this issue of
      Structure) describe how phosphorylation activates the protease activity of the
      deubiquitinating enzyme DUBA and how it inhibits caspase-6, respectively.

PMID- 22483105
TI  - Methionine scanning as an NMR tool for detecting and analyzing biomolecular
      interaction surfaces.
AB  - Methyl NMR spectroscopy is a powerful tool for studying protein structure,
      dynamics, and interactions. Yet difficulties with resonance assignment and the
      low abundance of methyl groups can preclude detailed NMR studies, particularly
      the determination of continuous interaction surfaces. Here we present a
      straightforward strategy that overcomes these problems. We systematically
      substituted solvent-exposed residues with reporter methionines in the expected
      binding site and performed chemical shift perturbation (CSP) experiments using
      methyl-TROSY spectra. We demonstrate the utility of this approach for the
      interaction between the HECT domain of the Rsp5p ubiquitin ligase and its cognate
      E2, Ubc4. Using these mutants, we could instantaneously assign all newly arising
      reporter methyl signals, determine the Ubc4 interaction surface on a per-residue
      basis, and investigate the importance of each individual mutation for ligand
      binding. Our data show that methionine scanning significantly extends the
      applicability, information content, and spatial resolution of methyl CSP
      experiments.

PMID- 22483107
TI  - The structure of human tripeptidyl peptidase II as determined by a hybrid
      approach.
AB  - Tripeptidyl-peptidase II (TPPII) is a high molecular mass (~5 MDa) serine
      protease, which is thought to act downstream of the 26S proteasome, cleaving
      peptides released by the latter. Here, the structure of human TPPII (HsTPPII) has
      been determined to subnanometer resolution by cryoelectron microscopy and single
      particle analysis. The complex is built from two strands forming a quasihelical
      structure harboring a complex system of inner cavities. HsTPPII particles exhibit
      some polymorphism resulting in complexes consisting of nine or of eight dimers
      per strand. To obtain deeper insights into the architecture and function of
      HsTPPII, we have created a pseudoatomic structure of the HsTPPII spindle using a
      comparative model of HsTPPII dimers and molecular dynamics flexible fitting.
      Analyses of the resulting hybrid structure of the HsTPPII holocomplex provide new
      insights into the mechanism of maturation and activation.

PMID- 22483106
TI  - Fabs enable single particle cryoEM studies of small proteins.
AB  - In spite of its recent achievements, the technique of single particle electron
      cryomicroscopy (cryoEM) has not been widely used to study proteins smaller than
      100 kDa, although it is a highly desirable application of this technique. One
      fundamental limitation is that images of small proteins embedded in vitreous ice
      do not contain adequate features for accurate image alignment. We describe a
      general strategy to overcome this limitation by selecting a fragment antigen
      binding (Fab) to form a stable and rigid complex with a target protein, thus
      providing a defined feature for accurate image alignment. Using this approach, we
      determined a three-dimensional structure of an ~65 kDa protein by single particle
      cryoEM. Because Fabs can be readily generated against a wide range of proteins by
      phage display, this approach is generally applicable to study many small proteins
      by single particle cryoEM.

PMID- 22483108
TI  - Solution structure analysis of the HPV16 E6 oncoprotein reveals a self
      association mechanism required for E6-mediated degradation of p53.
AB  - The viral oncoprotein E6 is an essential factor for cervical cancers induced by
      "high-risk" mucosal HPV. Among other oncogenic activities, E6 recruits the
      ubiquitin ligase E6AP to promote the ubiquitination and subsequent proteasomal
      degradation of p53. E6 is prone to self-association, which long precluded its
      structural analysis. Here we found that E6 specifically dimerizes through its N
      terminal domain and that disruption of the dimer interface strongly increases E6
      solubility. This allowed us to raise structural data covering the entire HPV16 E6
      protein, including the high-resolution NMR structures of the two zinc-binding
      domains of E6 and a robust data-driven model structure of the N-terminal domain
      homodimer. Interestingly, homodimer interface mutations that disrupt E6 self
      association also inactivate E6-mediated p53 degradation. These data suggest that
      E6 needs to self-associate via its N-terminal domain to promote the
      polyubiquitination of p53 by E6AP.

PMID- 22483109
TI  - How conformational dynamics of DNA polymerase select correct substrates:
      experiments and simulations.
AB  - Nearly every enzyme undergoes a significant change in structure after binding
      it's substrate. Experimental and theoretical analyses of the role of changes in
      HIV reverse transcriptase structure in selecting a correct substrate are
      presented. Atomically detailed simulations using the Milestoning method predict a
      rate and free energy profile of the conformational change commensurate with
      experimental data. A large conformational change occurring on a millisecond
      timescale locks the correct nucleotide at the active site but promotes release of
      a mismatched nucleotide. The positions along the reaction coordinate that decide
      the yield of the reaction are not determined by the chemical step. Rather, the
      initial steps of weak substrate binding and protein conformational transition
      significantly enrich the yield of a reaction with a correct substrate, whereas
      the same steps diminish the reaction probability of an incorrect substrate.

PMID- 22483110
TI  - Dissecting the kinematics of the kinesin step.
AB  - Kinesin walks processively on microtubules in an asymmetric hand-over-hand manner
      with each step spanning 16 nm. We used molecular simulations to determine the
      fraction of a single step due to conformational changes in the neck linker, and
      that due to diffusion of the tethered head. Stepping is determined largely by two
      energy scales, one favoring neck-linker docking and the other, epsilon(h)(MT-TH),
      between the trailing head (TH) and the microtubule. Neck-linker docking and an
      optimal value of epsilon(h)(MT-TH) are needed to minimize the probability that
      the TH takes side steps. There are three major stages in the kinematics of a
      step. In the first, the neck linker docks, resulting in ~(5-6) nm movements of
      the trailing head. The TH moves an additional (6-8) nm in stage II by anisotropic
      translational diffusion. In the third stage, spanning ~(3-4) nm, the step is
      complete with the TH binding to the alphabeta-tubulin binding site.

PMID- 22483111
TI  - Comparison between actin filament models: coarse-graining reveals essential
      differences.
AB  - The interconversion of actin between monomeric and polymeric forms is a
      fundamental process in cell biology that is incompletely understood, in part
      because there is no high-resolution structure for filamentous actin. Several
      models have been proposed recently; identifying structural and dynamic
      differences between them is an essential step toward understanding actin
      dynamics. We compare three of these models, using coarse-grained analysis of
      molecular dynamics simulations to analyze the differences between them and
      evaluate their relative stability. Based on this analysis, we identify key
      motions that may be associated with polymerization, including a potential
      energetic barrier in the process. We also find that actin subunits are
      polymorphic; during simulations they assume a range of configurations remarkably
      similar to those seen in recent cryoEM images.

PMID- 22483112
TI  - Asymmetric mode of Ca2+-S100A4 interaction with nonmuscle myosin IIA generates
      nanomolar affinity required for filament remodeling.
AB  - Filament assembly of nonmuscle myosin IIA (NMIIA) is selectively regulated by the
      small Ca2+-binding protein, S100A4, which causes enhanced cell migration and
      metastasis in certain cancers. Our NMR structure shows that an S100A4 dimer binds
      to a single myosin heavy chain in an asymmetrical configuration. NMIIA in the
      complex forms a continuous helix that stretches across the surface of S100A4 and
      engages the Ca2+-dependent binding sites of each subunit in the dimer. Synergy
      between these sites leads to a very tight association (K(D) ~1 nM) that is unique
      in the S100 family. Single-residue mutations that remove this synergy weaken
      binding and ameliorate the effects of S100A4 on NMIIA filament assembly and cell
      spreading in A431 human epithelial carcinoma cells. We propose a model for NMIIA
      filament disassembly by S100A4 in which initial binding to the unstructured NMIIA
      tail initiates unzipping of the coiled coil and disruption of filament packing.

PMID- 22483113
TI  - The structure of the XPF-ssDNA complex underscores the distinct roles of the XPF
      and ERCC1 helix- hairpin-helix domains in ss/ds DNA recognition.
AB  - Human XPF/ERCC1 is a structure-specific DNA endonuclease that nicks the damaged
      DNA strand at the 5' end during nucleotide excision repair. We determined the
      structure of the complex of the C-terminal domain of XPF with 10 nt ssDNA. A
      positively charged region within the second helix of the first HhH motif contacts
      the ssDNA phosphate backbone. One guanine base is flipped out of register and
      positioned in a pocket contacting residues from both HhH motifs of XPF.
      Comparison to other HhH-containing proteins indicates a one-residue deletion in
      the second HhH motif of XPF that has altered the hairpin conformation, thereby
      permitting ssDNA interactions. Previous nuclear magnetic resonance studies showed
      that ERCC1 in the XPF-ERCC1 heterodimer can bind dsDNA. Combining the two
      observations gives a model that underscores the asymmetry of the human XPF/ERCC1
      heterodimer in binding at an ss/ds DNA junction.

PMID- 22483114
TI  - Structural basis for the dual recognition of helical cytokines IL-34 and CSF-1 by
      CSF-1R.
AB  - Lacking any discernible sequence similarity, interleukin-34 (IL-34) and colony
      stimulating factor 1 (CSF-1) signal through a common receptor CSF-1R on cells of
      mononuclear phagocyte lineage. Here, the crystal structure of dimeric IL-34
      reveals a helical cytokine fold homologous to CSF-1, and we further show that the
      complex architecture of IL-34 bound to the N-terminal immunoglobulin domains of
      CSF-1R is similar to the CSF-1/CSF-1R assembly. However, unique conformational
      adaptations in the receptor domain geometry and intermolecular interface explain
      the cross-reactivity of CSF-1R for two such distantly related ligands. The
      docking adaptations of the IL-34 and CSF-1 quaternary complexes, when compared to
      the stem cell factor assembly, draw a common evolutionary theme for transmembrane
      signaling. In addition, the structure of IL-34 engaged by a Fab fragment reveals
      the mechanism of a neutralizing antibody that can help deconvolute IL-34 from CSF
      1 biology, with implications for therapeutic intervention in diseases with
      myeloid pathogenic mechanisms.

PMID- 22483115
TI  - Structure of the discoidin domain receptor 1 extracellular region bound to an
      inhibitory Fab fragment reveals features important for signaling.
AB  - The discoidin domain receptors, DDR1 and DDR2, are constitutively dimeric
      receptor tyrosine kinases that are activated by triple-helical collagen. Aberrant
      DDR signaling contributes to several human pathologies, including many cancers.
      We have generated monoclonal antibodies (mAbs) that inhibit DDR1 signaling
      without interfering with collagen binding. The crystal structure of the monomeric
      DDR1 extracellular region bound to the Fab fragment of mAb 3E3 reveals that the
      collagen-binding discoidin (DS) domain is tightly associated with the following
      DS-like domain, which contains the epitopes of all mAbs. A conserved surface
      patch in the DS domain outside the collagen-binding site is shown to be required
      for signaling. Thus, the active conformation of the DDR1 dimer involves collagen
      induced contacts between the DS domains, in addition to the previously identified
      association of transmembrane helices. The mAbs likely inhibit signaling by
      sterically blocking the extracellular association of DDR1 subunits.

PMID- 22483116
TI  - Crystal structures of Aureochrome1 LOV suggest new design strategies for
      optogenetics.
AB  - Aureochrome1, a signaling photoreceptor from a eukaryotic photosynthetic
      stramenopile, confers blue-light-regulated DNA binding on the organism. Its
      topology, in which a C-terminal LOV sensor domain is linked to an N-terminal DNA
      binding bZIP effector domain, contrasts with the reverse sensor-effector topology
      in most other known LOV-photoreceptors. How, then, is signal transmitted in
      Aureochrome1? The dark- and light-state crystal structures of Aureochrome1 LOV
      domain (AuLOV) show that its helical N- and C-terminal flanking regions are
      packed against the external surface of the core beta sheet, opposite to the FMN
      chromophore on the internal surface. Light-induced conformational changes occur
      in the quaternary structure of the AuLOV dimer and in Phe298 of the Hbeta strand
      in the core. The properties of AuLOV extend the applicability of LOV domains as
      versatile design modules that permit fusion to effector domains via either the N-
      or C-termini to confer blue-light sensitivity.

PMID- 22483117
TI  - Structural insight into the bacterial mucinase StcE essential to adhesion and
      immune evasion during enterohemorrhagic E. coli infection.
AB  - Mucin glycoproteins with large numbers of O-linked glycosylations comprise the
      mucosal barrier lining the mammalian gastrointestinal tract from mouth to gut. A
      critical biological function of mucins is to protect the underlying epithelium
      from infection. Enterohemorrhagic Escherichia coli (EHEC), the mediator of severe
      food- and water-borne disease, can breach this barrier and adhere to intestinal
      cells. StcE, a ~100 kDa metalloprotease secreted by EHEC, plays a pivotal role in
      remodeling the mucosal lining during infection. To obtain mechanistic insight
      into its function, we have determined the structure of StcE. Our data reveal a
      dynamic, multidomain architecture featuring an unusually large substrate-binding
      cleft and a prominent polarized surface charge distribution highly suggestive of
      an electrostatic role in substrate targeting. The observation of key conserved
      motifs in the active site allows us to propose the structural basis for the
      specific recognition of alpha-O-glycan-containing substrates. Complementary
      biochemical analysis provides further insight into its distinct substrate
      specificity and binding stoichiometry.

PMID- 22483118
TI  - Detection of spatial correlations in protein structures and molecular complexes.
AB  - Protein structures are frequently related by spectacular and often surprising
      similarities. Structural correlations among protein chains are routinely detected
      by various structure-matching techniques, but the comparison of oligomers and
      molecular complexes is largely uncharted territory. Here we solve the structure
      matching problem for oligomers and large molecular aggregates, including the
      largest molecular complexes known today. We provide several challenging examples
      that cannot be handled by conventional structure-matching techniques and we
      report on a number of remarkable correlations. The examples cover the cell
      puncturing device of bacteriophage T4, the secretion system of P. aeruginosa,
      members of the dehydrogenase family, DNA clamps, ferredoxin iron-storage cages,
      and virus capsids.

PMID- 22483119
TI  - An asymmetry-to-symmetry switch in signal transmission by the histidine kinase
      receptor for TMAO.
AB  - The osmoregulator trimethylamine-N-oxide (TMAO), commonplace in aquatic
      organisms, is used as the terminal electron acceptor for respiration in many
      bacterial species. The TMAO reductase (Tor) pathway for respiratory catalysis is
      controlled by a receptor system that comprises the TMAO-binding protein TorT, the
      sensor histidine kinase TorS, and the response regulator TorR. Here we study the
      TorS/TorT sensor system to gain mechanistic insight into signaling by histidine
      kinase receptors. We determined crystal structures for complexes of TorS sensor
      domains with apo TorT and with TorT (TMAO); we characterized TorS sensor
      associations with TorT in solution; we analyzed the thermodynamics of TMAO
      binding to TorT-TorS complexes; and we analyzed in vivo responses to TMAO through
      the TorT/TorS/TorR system to test structure-inspired hypotheses. TorS-TorT(apo)
      is an asymmetric 2:2 complex that binds TMAO with negative cooperativity to form
      a symmetric active kinase.

PMID- 22483121
TI  - Prenatal diagnosis of atypical adrenal neuroblastoma with pulmonary metastases is
      possible: Impact on the assessment of prenatal prognosis.

PMID- 22483122
TI  - Radiotherapy and radiology: joint efforts for modern radiation planning and
      practice.
AB  - With new irradiation techniques, the dose can be better matched to the contours
      of the tumour. The corollary is that greater precision is required. Recent
      intercomparison studies of treatment plans have emphasized the need to harmonise
      contouring practices. More of a consensus approach is based on using adaptive
      imaging modalities, expert group recommendations and automatic segmentation
      atlases, on harmonisation of dosimetric decisions through employing exhaustive
      nomograms for organs at risk, and on indexes for choosing optimal treatment
      plans. On another level, quality assurance and data pooling programmes have been
      set up, making use of DICOM-RT data transfer (image networks). The combination of
      several irradiation techniques (for example, intensity-modulated conformal
      radiation therapy plus CyberKnife((r)) boost and re-irradiation), making it
      possible to irradiate tumours better, requires the cumulative doses to be
      recorded by dose summation software. Real awareness has been achieved in recent
      years as regards improving the quality of treatment, pooling data and harmonising
      practices.

PMID- 22483120
TI  - Phosphorylation regulates assembly of the caspase-6 substrate-binding groove.
AB  - Caspases, a family of apoptotic proteases, are increasingly recognized as being
      extensively phosphorylated, usually leading to inactivation. To date, no
      structural mechanism for phosphorylation-based caspase inactivation is available,
      although this information may be key to achieving caspase-specific inhibition.
      Caspase-6 has recently been implicated in neurodegenerative conditions including
      Huntington's and Alzheimer's diseases. A full understanding of caspase-6
      regulation is crucial to caspase-6-specific inhibition. Caspase-6 is
      phosphorylated by ARK5 kinase at serine 257 leading to suppression of cell death
      via caspase-6 inhibition. Our structure of the fully inactive phosphomimetic
      S257D reveals that phosphorylation results in a steric clash with P201 in the L2'
      loop. Removal of the proline side chain alleviates the clash resulting in nearly
      wild-type activity levels. This phosphomimetic-mediated steric clash causes
      misalignment of the substrate-binding groove, preventing substrate binding.
      Substrate-binding loop misalignment appears to be a widely used regulatory
      strategy among caspases and may present a new paradigm for caspase-specific
      control.

PMID- 22483123
TI  - Friendship.

PMID- 22483124
TI  - A crisis of faith? A review of simulation in teaching team-based, crisis
      management skills to surgical trainees.
AB  - BACKGROUND: Team-based training using crisis resource management (CRM) has gained
      popularity as a strategy to minimize the impact of medical error during critical
      events. The purpose of this review was to appraise and summarize the design,
      implementation, and efficacy of peer-reviewed, simulation-based CRM training
      programs for postgraduate trainees (residents). METHODS: Two independent
      reviewers conducted a structured literature review, querying multiple medical and
      allied health databases from 1950 to May 2010 (MEDLINE, EMBASE, CINAHL, EBM, and
      PsycINFO). We included articles that (1) were written in English, (2) were
      published in peer-reviewed journals, (3) included residents, (4) contained a
      simulation component, and (5) included a team-based component. Peer-reviewed
      articles describing the implementation of CRM instruction were critically
      appraised using the Kirkpatrick framework for evaluating training programs.
      RESULTS: Fifteen studies involving a total of 404 residents met inclusion
      criteria; most studies reported high resident satisfaction for CRM training. In
      several CRM domains, residents demonstrated significant improvements after
      training, which did not decay over time. With regard to design, oral feedback may
      be equivalent to video feedback and single-day interventions may be as
      efficacious as multiple-day interventions for residents. No studies demonstrated
      a link between simulation-based CRM training and performance during real-life
      critical events. CONCLUSIONS: The findings support the utility of CRM programs
      for residents. A high degree of satisfaction and perceived value reflect robust
      resident engagement. The iteration of themes from our review provides the basis
      for the development of best practices in curricula design. A dearth of well
      designed, randomized studies preclude the quantification of impact of simulation
      based training in the clinical environment.

PMID- 22483125
TI  - A simulator model for sacroiliac screw placement.
AB  - OBJECTIVE: Fixation with percutaneously placed sacroiliac screws has become a
      well-established technique for fixation of the posterior pelvic ring in the
      proper clinical setting. This technique, however, carries with it the risk of
      iatrogenic injury to neurovascular structures with aberrant screw placement.
      Given the potential risks involved with this technique, a model whereby the
      psychomotor skills involved could be refined before entering the operating room
      may be of benefit. The purpose of the current study is (1) to describe a
      simulator model for SI screw placement that can be assembled from readily
      available equipment and (2) to attempt to demonstrate the construct validity of
      such a simulator. DESIGN: A simulator was assembled using readily available
      equipment found in the hospital and at a hardware store, and the cost of set up
      is less than $50. Orthopedic surgeons and novice operators were then observed
      using the simulator and results were recorded. SETTING: Tertiary referral
      teaching hospital. PARTICIPANTS: Orthopedic surgery residents, resident faculty,
      x-ray technicians. RESULTS: This simulator has been found to be a safe and
      effective model for teaching junior residents the technique of sacroiliac (SI)
      screw placement. An added benefit to this module is that it helps train new C-arm
      technicians to learn how to obtain the necessary views for this procedure.
      CONCLUSIONS: This model can be a valuable component of orthopedic training
      programs whereby technical and psychomotor skills necessary for percutaneous SI
      screw placement can be developed in a controlled setting.

PMID- 22483126
TI  - An analysis of the Orthopaedic In-Training Examination rehabilitation section.
AB  - OBJECTIVE: One subject tested by the Orthopaedic In-Training Examination (OITE)
      is rehabilitation. Our purpose was to analyze the OITE's rehabilitation section
      to (1) identify the rehabilitation subjects that are tested, (2) evaluate trainee
      performance on this section, and (3) evaluate the literature cited for this
      section as an aide to the trainee preparation for future OITE examinations.
      DESIGN: This study included OITE examinations from 2004 through 2009. The
      rehabilitation sections of these examinations were analyzed for content, type of
      questions asked (taxonomy 1: direct recall; taxonomy 2: diagnosis; taxonomy 3:
      evaluation/decision making and development of a treatment plan), and literature
      cited. The mean score in the rehabilitation section of the OITE from 2004 to 2009
      was also evaluated, and literature citations were tabulated. SETTING: Orthopaedic
      surgery residency. RESULTS: In the 2004-2009 OITE examinations, a total of 1619
      questions were administered, of which 53 (3.3%) related to rehabilitation. The
      most common rehabilitation questions assessed knowledge of prosthetic/orthotics
      (20.8%) and neuro-orthopedics (20.8%). Other questions addressed amputation
      (18.9%), physical therapy treatment and outcomes (18.9%), rehabilitation
      terminology (9.4%), and spinal cord injury (7.7%). Most frequently, the questions
      evaluated the trainee's direct recall of the subject (51%), evaluation/decision
      making and development of a treatment plan (30.1%), and diagnosis (18.9%). The
      mean score in the rehabilitation section of the OITE from 2004 through 2009 was
      54.1% (range, 40% to 77.8%). A total of 53 references was used. The 3 most common
      references were the Journal of Bone and Joint Surgery-American Volume (10),
      Orthopaedic Knowledge Update (volumes 7 through 9) (8), and Clinical Orthopaedics
      and Related Research (7). CONCLUSION: To our knowledge, our study is the first to
      analyze the rehabilitation section of the OITE. Our results will help the trainee
      prepare for the examination by focusing on the appropriate content and
      literature.

PMID- 22483127
TI  - Attitudes and practices of surgery residency program directors toward the use of
      social networking profiles to select residency candidates: a nationwide survey
      analysis.
AB  - OBJECTIVE: To determine whether residency program directors (PDs) of general
      surgery and surgical subspecialties review social networking (SN) websites during
      resident selection. DESIGN: A 16-question survey was distributed via e-mail
      (Survey Monkey, Palo Alto, California) to 641 PDs of general surgery and surgical
      subspecialty residency programs accredited by the Accreditation Council for
      Graduate Medical Education (ACGME). SETTING: Institutions with ACGME-accredited
      general surgery and surgical subspecialty residency programs. PARTICIPANTS: PDs
      of ACGME-accredited general surgery and surgical subspecialty residency programs.
      RESULTS: Two hundred fifty (39%) PDs completed the survey. Seventeen percent (n =
      43) of respondents reported visiting SN websites to gain more information about
      an applicant during the selection process, leading 14 PDs (33.3%) to rank an
      applicant lower after a review of their SN profile. PDs who use SN websites
      currently are likely to continue (69%), whereas those who do not use SN currently
      might do so in the future (yes 5.4%, undecided 44.6%). CONCLUSIONS: Online
      profiles displayed on SN websites provide surgery PDs with an additional avenue
      with which to evaluate highly competitive residency applicants. Applicants should
      be aware of the expansion of social media into the professional arena and the
      increasing use of these tools by PDs. SN profiles should reflect the professional
      standards to which physicians are held while highlighting an applicant's
      strengths and academic achievements.

PMID- 22483128
TI  - Attracting students to surgical careers: preclinical surgical experience.
AB  - OBJECTIVES: Along with a decline in interest in general surgery among United
      States medical school graduates, reports indicate a decrease in the amount of
      time students are spending on their surgical clerkship. In an effort to offer
      early exposure to general surgery as well as to equip students with the basic
      surgical skills that will enhance their third-year clerkship experience, we
      developed a preclinical surgical experience. Students were surveyed to determine
      whether the surgical selective changed student level of comfort with basic
      surgical skills. STUDY DESIGN: Surveys were administered, preexperience and
      postexperience to the medical students enrolled in the surgery selective. The
      students were asked to rate their comfort level with 12 unique surgical skills.
      Comfort with the task was evaluated using a 10-point Likert scale. Analyses were
      conducted to evaluate the impact of the surgical experience on student comfort
      levels with the surgical skills. RESULTS: The self-reported comfort levels of
      students increased significantly after the experience in all 12 areas. The
      greatest change in comfort level (greater than or equal to mean difference of 4)
      occurred in the surgical technique categories: knot tying (mean difference: 4.9,
      p < 0.0001), suturing (mean difference: 4.85, p < 0.0001), correctly making an
      incision (mean difference: 4.95, p < 0.0001), using a needle driver (mean
      difference: 5.35, p < 0.0001), holding pickups (mean difference: 4.6, p <
      0.0001), use of laparoscopic instruments (mean difference: 4.8, p < 0.0001), and
      use of surgical simulators (mean difference: 6.0, p < 0.0001). CONCLUSIONS: Our
      preclinical surgical experience serves as a model of an effective modality
      providing early exposure to general surgery. The experience provides trainees
      with basic surgical skills well before they begin their third-year clerkships.

PMID- 22483129
TI  - Computer-aided feedback of surgical knot tying using optical tracking.
AB  - BACKGROUND: Quantifying the information content of hand motion during surgical
      knot tying using information theory based entropy measures enables the comparison
      of different groups: novice and expert. We hypothesized that complexity would
      differ between the 2 groups and predicted based on motor learning models that
      complexity/information would reduce with increased expertise. METHODS: Six
      degrees of freedom hand-motion data during surgical knot tying were acquired
      using an infrared optical hand tracking device. Multiple data samples were
      obtained from 2 groups: novice (third-year medical students) and expert
      (attending surgeons). After preprocessing each knot tying data sample into a
      binary symbolic time series, 3 nonlinear complexity measures were calculated:
      Lempel Ziv complexity, Shannon entropy, and Renyi entropy. The Shannon and Renyi
      entropies were calculated using a word length of 6. A Student t test was used to
      test whether the 2 groups were from the same population when using these entropy
      measures, applying a p value of 0.05 to reject the null hypothesis. RESULTS: The
      expert surgeons were found to have less complex patterns of motion compared with
      the novice group. This finding was statistically significant using Lempel Ziv
      complexity (p = 0.004), Shannon entropy (p = 0.006), and Renyi entropy with q = 2
      (p = 0.006). Using Renyi entropy with q = 0.5, the 2 groups were not
      significantly different (p = 0.26). CONCLUSIONS: The ability to separate novice
      from expert populations during surgical knot tying using information theory
      entropy measures could form the basis of a low-cost educational tool to provide
      feedback and to assess skill acquisition using low-fidelity bench models.

PMID- 22483130
TI  - Do international rotations make surgical residents more resource-efficient? A
      preliminary study.
AB  - OBJECTIVE: Interest in international surgery among general surgery residents in
      the United States has been shown in several publications. Several general surgery
      residency programs have reported their experiences with international surgery
      rotations (ISRs). Learning to use limited resources more efficiently is often
      cited as a benefit of such rotations. We hypothesized that general surgery
      residents become more resource efficient after they have completed an ISR. STUDY
      DESIGN: Laboratory, radiologic, and diagnostic studies ordered on 2900 patients
      by 21 general surgery residents over 65 months at a single institution were
      analyzed retrospectively. The patient populations they wrote orders on were
      assessed for similarity in age, gender, and diagnoses. The outcomes in those
      patient populations were assessed by duration of stay and in-hospital mortality.
      Six (29%) of these residents (ISR residents) completed a 1-month ISR during their
      third year of residency. Their orders were compared with their classmates who did
      not participate in an ISR (NISR residents). The results were compared between the
      2 cohorts from both before and after their international rotations. An analysis
      focused on comparing the changes from pre-ISR to post-ISR. A survey was also sent
      after objective data were collected to all residents and alumni involved in the
      study to assess their subjective perception of changes in their resource
      efficiency and to characterize their ISRs. RESULTS: Patient populations were
      similar in terms of demographics and diagnoses. ISR residents generated an
      average of $122 less in orders per patient per month after their ISR compared
      with before. NISR residents generated an average of $338 more in orders per
      patient per month after the ISRs compared with before (p = 0.04). Pre-ISR order
      charges were statistically similar. Similar results were observed when
      radiologic/diagnostic study orders were analyzed independently. Differences in
      outcomes were statistically insignificant. The survey revealed that most of the
      ISR residents perceived that their attitude toward ordering tests and
      laboratories was influenced greatly by their ISR, and all the ISR residents
      perceived that they became more resource efficient than their peers after their
      ISRs. CONCLUSION: These preliminary findings seem to indicate increased resource
      efficiency among general surgery residents who completed an ISR. However, the
      sample size of residents was small, and we could not establish conclusively a
      causal relationship to their ISRs. A more extensive study is needed if reliable
      conclusions are to be drawn regarding the effect of ISRs on the resource
      efficiency of residents.

PMID- 22483131
TI  - Do medical students understand brain death? A survey study.
AB  - BACKGROUND: A lack of understanding of brain death has been demonstrated among
      physicians, and may stem from knowledge deficits at the medical school level. The
      authors sought to evaluate current understanding of brain death and knowledge
      gaps among U.S. medical students at a single center. METHODS: Using a validated
      "Understanding Brain Death" survey tool, the authors surveyed the student body at
      an accredited four year medical school. A score of 5/5 on this scale indicated an
      expert level of understanding. The investigators identified areas of knowledge
      gaps, and compared brain death expertise throughout the curriculum progression.
      RESULTS: The overall response rate was 69% (212 of 306 students). Mean scores
      were 3.1, 3.9, 4.1, and 4.0 (out of 5) among first through fourth year classes
      respectively. Understanding of brain death differed across the medical school
      classes (p <0.0001). 33% (N=70) of all students attained scores of 5 indicating
      an expert level of understanding brain death. By class; 18% of first year
      students demonstrated expert levels of understanding, compared to 31% of second
      year students, 48% of third year students, and 39% of fourth year students.
      CONCLUSIONS: The level of understanding of brain death is low among the student
      body in a four year accredited U.S. medical school. This knowledge gap persists
      among graduating students as most do not attain an expert understanding of brain
      death. A more comprehensive brain death curriculum should be implemented in order
      to adequately equip physicians with this fundamental knowledge.

PMID- 22483132
TI  - Educational value of morbidity and mortality (M&M) conferences: are minor
      complications important?
AB  - BACKGROUND: Often, minor complications are not reported in morbidity and
      mortality (M&M) conference because they are considered insignificant to patient
      outcome. As part of an effort to improve the quality of the M&M conference, we
      sought to integrate a specific, focused intervention to improve the reporting of
      minor complications and to evaluate the perception of its educational value.
      MATERIALS AND METHODS: To provide evidence-based training in recognizing,
      treating, and preventing minor complications, a presentation strategy was
      created. Surgical faculty identified 20 complications as minor complications.
      Each month, a junior resident was assigned to give a 10-minute presentation,
      assessing 1 of the 20 minor complications in depth during the M&M conference. To
      assess the impact of the intervention, we surveyed residents and faculty about
      the educational value of M&M conferences before and after implementation.
      RESULTS: Before introducing minor complication presentations into the M&M
      conference, only 58% of respondents indicated that minor complications should be
      reported at the conference. After the changes were implemented in minor
      complication reporting, 95% of respondents said that minor complications should
      be reported (p < 0.01). Eighty-nine percent of respondents found the minor
      complication presentations to be educationally beneficial. In addition,
      postsurvey respondents were also more likely than presurvey respondents to
      identify that a purpose of an M&M conference was to improve patient care (29% vs
      71%, p < 0.05). CONCLUSIONS: A formal, evidence-based presentation of minor
      complications can increase both the faculty and residents' perception of the
      importance of reporting minor complications at an M&M conference. Focused minor
      complication reporting should be incorporated into M&M curriculum.

PMID- 22483133
TI  - Gaming used as an informal instructional technique: effects on learner knowledge
      and satisfaction.
AB  - BACKGROUND: Jeopardy!, Concentration, quiz bowls, and other gaming formats have
      been incorporated into health sciences classroom and online education. However,
      there is limited information about the impact of these strategies on learner
      engagement and outcomes. To address this gap, we hypothesized that gaming would
      lead to a significant increase in retained short- and long-term medical knowledge
      with high learner session satisfaction. METHODS: Using the Jeopardy! game show
      model as a primary instructional technique to teach geriatrics, 8 PGY2 General
      Surgery residents were divided into 2 teams and competed to provide the
      "question" to each stated "answer" during 5 protected block curriculum units (1
      h/U). A surgical faculty facilitator acted as the game host and provided feedback
      and brief elaboration of quiz answers/questions as necessary. Each quiz session
      contained two 25-question rounds. Paper-based pretests and posttests contained
      questions related to all core curriculum unit topics with 5 geriatric gaming
      questions per test. Residents completed the pretests 3 days before the session
      and a delayed posttest of geriatric topics on average 9.2 weeks (range, 5-12
      weeks) after the instructional session. The cumulative average percent correct
      was compared between pretests and posttests using the Student t test. The
      residents completed session evaluation forms using Likert scale ratings after
      each gaming session and each protected curriculum block to assess educational
      value. RESULTS: A total of 25 identical geriatric preunit and delayed postunit
      questions were administered across the instructional sessions. The combined
      pretest average score across all 8 residents was 51.5% for geriatric topics
      compared with 59.5% (p = 0.12) for all other unit topics. Delayed posttest
      geriatric scores demonstrated a statistically significant increase in retained
      medical knowledge with an average of 82.6% (p = 0.02). The difference between
      delayed posttest geriatric scores and posttest scores of all other unit topics
      was not significant. Residents reported a high level of satisfaction with the
      gaming sessions: The average session content rating was 4.9 compared with the
      overall block content rating of 4.6 (scale, 1-5, 5 = Outstanding). CONCLUSIONS:
      The quiz type and competitive gaming sessions can be used as a primary
      instructional technique leading to significant improvements in delayed posttests
      of medical knowledge and high resident satisfaction of educational value.
      Knowledge gains seem to be sustained based on the intervals between the
      interventions and recorded gains.

PMID- 22483134
TI  - High-fidelity, low-cost, automated method to assess laparoscopic skills
      objectively.
AB  - BACKGROUND: We sought to define the extent to which a motion analysis-based
      assessment system constructed with simple equipment could measure technical skill
      objectively and quantitatively. METHODS: An "off-the-shelf" digital video system
      was used to capture the hand and instrument movement of surgical trainees
      (beginner level = PGY-1, intermediate level = PGY-3, and advanced level = PGY
      5/fellows) while they performed a peg transfer exercise. The video data were
      passed through a custom computer vision algorithm that analyzed incoming pixels
      to measure movement smoothness objectively. RESULTS: The beginner-level group had
      the poorest performance, whereas those in the advanced group generated the
      highest scores. Intermediate-level trainees scored significantly (p < 0.04)
      better than beginner trainees. Advanced-level trainees scored significantly
      better than intermediate-level trainees and beginner-level trainees (p < 0.04 and
      p < 0.03, respectively). CONCLUSIONS: A computer vision-based analysis of
      surgical movements provides an objective basis for technical expertise-level
      analysis with construct validity. The technology to capture the data is simple,
      low cost, and readily available, and it obviates the need for expert human
      assessment in this setting.

PMID- 22483135
TI  - Is the evaluation of the personal statement a reliable component of the general
      surgery residency application?
AB  - BACKGROUND: Each year, fourth-year medical students spend considerable time
      writing and rewriting their personal statements. However, there is little
      evidence of what role the personal statement plays in deciding which applicants
      will be invited for an interview. OBJECTIVE: To evaluate the inter-rater
      reliability of a surgical selection committee's ratings for both the personal
      statement and the application summary parts of the residency application. DESIGN:
      We completed a retrospective analysis of the 2007-2008 Scott & White surgical
      residency application pool. From a total pool of 174 residency applications, we
      selected 8 (5%) applications randomly to be evaluated by 4 experienced members of
      the selection committee. The 4 committee members rated each personal statement on
      a 7-point scale, from "negative-would not invite for an interview" to "positive
      will invite for an interview." They rated respective application summaries
      separately on a similar 7-point scale. Committee members also listed their top
      three reasons for assigning their scores. METHODS: Rating scores for the personal
      statements and the applications were analyzed for inter-rater correlation. The
      qualitative data (ie, reasons for the scores) were reviewed to help the
      investigators profile the reasons given for very positive and very negative
      scores. RESULTS: For the application summaries, the correlations between each
      pair of raters ranged from 0.79 to 0.94 with an overall average of 0.88. For the
      personal statements, inter-rater correlations ranged from -0.83 to 0.63 with an
      overall average of -0.09. CONCLUSION: These results demonstrate that the personal
      statements lacked objective criteria for evaluation.

PMID- 22483136
TI  - Is there a digital generation gap for e-learning in plastic surgery?
AB  - BACKGROUND: Some authors have claimed that those plastic surgeons born between
      1965 and 1979 (generation X, or Gen-X) are more technologically able than those
      born between 1946 and 1964 (Baby Boomers, or BB). Those born after 1980, which
      comprise generation Y (Gen-Y), might be the most technologically able and most
      demanding for electronic learning (e-learning) to support their education and
      training in plastic surgery. These differences might represent a "digital
      generation gap" and would have practical and financial implications for the
      development of e-learning. OBJECTIVES: The aim of this study was to survey
      plastic surgeons on their experience and preferences in e-learning in plastic
      surgery and to establish whether there was a difference between different
      generations. DESIGN: Online survey (e-survey) of plastic surgeons within the UK
      and Ireland was used for this study. METHODS: In all, 624 plastic surgeons were
      invited by e-mail to complete an e-survey anonymously for their experience of e
      learning in plastic surgery, whether they would like access to e-learning and, if
      so, whether this should this be provided nationally, locally, or not at all. By
      stratifying plastic surgeons into three generations (BB, Gen-X, and Gen-Y), the
      responses between generations were compared using the chi(2)-test for linear
      trend. A p value < 0.05 was considered to be statistically significant. RESULTS:
      Of the 624 plastic surgeons contacted, 237 plastic surgeons completed the survey
      (response rate, 38%), but data from 2 surgeons were excluded. For the remaining
      235 plastic surgeons, no evidence was found of statistically significant linear
      trends between by generation and either experience, access, or provision of e
      learning. CONCLUSIONS: These findings refute the claim that there are differences
      in the experience of e-learning of plastic surgeons by generation. Furthermore,
      there is no evidence that there are differences in whether there should be access
      to e-learning and how e-learning should be provided for different generations of
      plastic surgeons.

PMID- 22483137
TI  - Lessons learned from an unusual case of inflammatory breast cancer.
AB  - Inflammatory breast cancer (IBC) is a rare breast malignancy that is associated
      with poor long-term outcomes despite aggressive surgical and chemotherapeutic
      interventions. We recently treated a 56-year-old woman with right-sided IBC and
      biopsy-proven cutaneous metastases to her back and left breast. She underwent
      chemotherapy, bilateral modified radical mastectomy, and radiation therapy. One
      year after diagnosis, she is currently disease-free based on positron-emission
      tomography (PET) imaging and repeat skin biopsies. To provide insight into the
      management of IBC, we present this interesting case with a reflection on
      important lessons to be learned.

PMID- 22483138
TI  - Limiting PGY 1 residents to 16 hours of duty: review and report of a workshop.
AB  - BACKGROUND: In 2003, the Accreditation Council for Graduate Medical Education
      (ACGME) instituted limits on duty hours. Residents were restricted to working 80
      hours/week and limited to 24 hours of continuous patient care. Effective July
      2011, an additional restriction will be instituted for PGY 1 residents limiting
      continuous duty to 16 hours maximum. OBJECTIVE: Prospective evaluation of the
      impact of the upcoming work shift limitations for PGY 1 residents.
      DESIGN/SETTING/PARTICIPANTS: Review of literature and discussions among program
      directors, program coordinators, and residents on the effects of prior
      limitations of duty hours, as a point of reference, to manage the changes of duty
      hours for PGY 1 residents during a workshop at the Association of Program
      Directors in Surgery Annual Meeting. RESULTS: Work-hour restrictions necessitate
      a change from the traditional 24-hour on-duty call schedule for PGY 1 residents.
      The benefits to patients of being treated by less tired doctors working in shifts
      may be offset by communication failures from poor handoffs, rendering the system
      prone to adverse events/near misses. With additional work-hour restrictions, it
      is imperative to anticipate problems and deal with them effectively. Continued
      reevaluation of the handoff system and efforts made to decrease the number of
      preventable adverse events that typically occur during periods of cross coverage
      should be undertaken. Labor costs to carry out these new restrictions are
      predictably high but can be made budget neutral if improvement in patient care
      leads to reduction in the costs of corrective actions. CONCLUSIONS: Residency
      programs have adapted to the 2003 work-hour restrictions without apparent ill
      effect. We must study the effects of the July 2011 requirements prospectively as
      the traditional frontline physicians (PGY 1 residents) will no longer be
      available for 24-hour duty shifts.

PMID- 22483139
TI  - Medical students pursuing surgical fields have no greater innate motor dexterity
      than those pursuing nonsurgical fields.
AB  - INTRODUCTION: Medical students pursue different career paths based on a variety
      of factors. We sought to examine the impact of innate manual dexterity, both
      perceived and objective, on the career interests of medical students. METHODS:
      Third-year medical students from the University of California, Irvine were
      recruited for this study. Subjects completed a pretest questionnaire followed by
      assessment of gross and fine motor dexterity using the Purdue Pegboard test. A
      total of 6 independent trials were performed, 3 for each hand. The scores were
      recorded as an integer value between 0 and 25. A statistical analysis was
      performed using student t tests, the Fischer exact test, or the chi(2) test,
      where appropriate. RESULTS: A total of 100 students completed the questionnaire
      while 58 completed the dexterity testing. Students interested in a surgical field
      (SF) were similar in handedness, gender, video game exposure, and learning style
      as those interested in a nonsurgical field (NSF). In the SF group, "personal
      skill set" was reported as the most common factor influencing career selection,
      and "interest in disease process/patient population" was reported most commonly
      by NSF students (p = 0.015). Although a perceived innate manual dexterity was
      higher among SF students compared with NSF students (p = 0.032), no significant
      objective differences were found in right hand, left hand, or combined dexterity
      scores. CONCLUSIONS: Perceived "personal skill set" may influence strongly a
      medical student's career choice. Despite greater perceived manual dexterity,
      students interested in an SF do not have greater objective innate manual
      dexterity than those interested in an NSF.

PMID- 22483140
TI  - Nomogram to predict successful placement in surgical subspecialty fellowships
      using applicant characteristics.
AB  - PURPOSE: The purpose of the study was to develop a model that predicts an
      individual applicant's probability of successful placement into a surgical
      subspecialty fellowship program. METHODS: Candidates who applied to surgical
      fellowships during a 3-year period were identified in a set of databases that
      included the electronic application materials. RESULTS: Of the 1281 applicants
      who were available for analysis, 951 applicants (74%) successfully placed into a
      colon and rectal surgery, thoracic surgery, vascular surgery, or pediatric
      surgery fellowship. The optimal final prediction model, which was based on a
      logistic regression, included 14 variables. This model, with a c statistic of
      0.74, allowed for the determination of a useful estimate of the probability of
      placement for an individual candidate. CONCLUSIONS: Of the factors that are
      available at the time of fellowship application, 14 were used to predict
      accurately the proportion of applicants who will successfully gain a fellowship
      position.

PMID- 22483141
TI  - Perceived benefits of a transplant surgery experience to general surgery
      residency training.
AB  - OBJECTIVES: The benefit of a solid-organ transplant experience during general
      surgical training has been questioned recently. In 2008, in response to an
      American Board of Surgery (ABS) directive, a survey was conducted by the
      Association of Program Directors in Surgery (APDS) in coordination with the
      American Society of Transplant Surgeons (ASTS) to determine the perceived value
      of a transplant surgery rotation to program directors and residents. With the aim
      of providing additional insight, we conducted a separate study, independent of
      the ABS and ASTS, to ascertain resident perceptions regarding the specific skill
      sets that they acquire during their transplant surgery rotations and their
      applicability to other surgical subspecialties. METHODS: A preliminary, 51-item,
      web-based questionnaire was completed by 69.6% of residents in nationally
      accredited general surgery programs who accessed the survey. The results were
      examined using appropriate statistical methods to determine associations between
      answers. RESULTS: Although only 16.6% of participants responded that they were
      considering a career in transplantation, 63.4% answered that the skill sets
      acquired during this rotation would assist them in their surgical careers
      regardless of their chosen specialty. Most (65.5%) respondents answered that the
      techniques learned were directly applicable to other specialties, such as
      vascular, urologic, trauma, and hepatobiliary surgery. Free response questions
      indicated that the most common criticisms of this rotation were the limited
      amount of operative participation, lack of teaching by attendings, and lifestyle
      limitations. CONCLUSIONS: The results of this study indicate that surgery
      residents are conflicted regarding their transplant surgery experience but regard
      it as a beneficial addition to their training. Most respondents indicated also
      that these skills were transferable directly to other surgical specialties.

PMID- 22483142
TI  - Practice-based learning and improvement: a two-year experience with the reporting
      of morbidity and mortality cases by general surgery residents.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) core
      competency of practice-based learning and improvement can be assessed with
      surgical Morbidity and Mortality Conference (MMC). We aim to describe the MMC
      reporting patterns of general surgery residents, describe the adverse event rate
      for patients and compare that with existing published rates, and describe the
      nature of our institutional adverse events. We hypothesize that reporting
      patterns and incidence rates will remain constant over time. METHODS: In this
      retrospective cohort study, archived MMC case lists were evaluated from January
      1, 2009 to December 31, 2010. The reporting patterns of the residents, the
      adverse event ratios, and the specific categories of adverse events were
      described over the academic years. chi(2) and Fisher's exact tests were used to
      compare across academic years, using an alpha = 0.05. RESULTS: There were 85
      surgical MMC case lists evaluated. Services achieved a reporting rate above 80%
      (p < 0.001). The most consistent reporting was done by postgraduate year (PGY) 5
      level chief residents for all services (p > 0.05). Out of 11,368 patients
      evaluated from complete MMC submissions, 289 patients had an adverse event
      reported (2.5%). This was lower than published reporting rates for patient
      adverse event rates (p < 0.001). Adverse event rates were consistent for
      residents at the postgraduate year 2, 4, and 5 levels for all services (p >
      0.05). Over 2 years, 522 adverse events were reported for 461 patients. A
      majority of adverse events were from death (24.1%), hematologic and/or vascular
      events (16.7%), and gastrointestinal system events (16.1%). CONCLUSIONS: Surgery
      resident MMC reporting patterns and adverse event rates are generally stable over
      time. This study shows which adverse event cases are important for chief
      residents to report.

PMID- 22483143
TI  - Send it: study of e-mail etiquette and notions from doctors in training.
AB  - OBJECTIVES: Worldwide, more than 247 billion e-mails are sent each day. Little
      empiric evidence is available to guide how e-mail presentation style, tone, and
      content affect e-mail recipients and whether these factors impact opinions about
      the sender and the rapidity of response. In a study of physicians in training
      assessing a series of 100 e-mail examples, we examined the following: (1)
      formatting characteristics most and least endorsed, (2) impression of the sender
      based on the e-mail itself, and (3) factors associated with the decision to
      respond. We reasoned that our study would provide empiric data to support
      recommendations for e-mail etiquette, focusing specifically on doctors in
      training. DESIGN: Cross-sectional survey study. SETTING: Division of Orthopaedic
      Surgery at McMaster University, Hamilton, Ontario, Canada. PARTICIPANTS: After
      each e-mail, the participating surgical residents completed a series of questions
      focusing on their impression of the e-mail appearance, their perception of the
      sender, and their motivation to respond to the e-mail. RESULTS: Thirty-two
      residents participated in this study. The responses indicate that the key
      negatively endorsed features of the e-mails included the use of colored
      backgrounds (84%), difficult-to-read font (83%), lack of a subject header (55%),
      opening salutations without recipient names (50%), or no salutation at all (42%).
      The senders of negatively endorsed e-mails were perceived by participants as
      inefficient (p = 0.03), unprofessional (p < 0.001), and irritating (p = 0.007). E
      mails with overall positive endorsements were significantly more likely to have
      the participants perceive the e-mail senders as professional (p < 0.001),
      pleasant (p = 0.048), and kind (p = 0.059). The participants were 2.6-fold more
      likely to respond immediately when they perceived e-mails as favorable compared
      with disliking them (42% vs 16% of responses, respectively, p < 0.001).
      CONCLUSION: The e-mails perceived as being disliked overall are likely to result
      in a negative perception of the sender and delays in response time.

PMID- 22483144
TI  - The production of audiovisual teaching tools in minimally invasive surgery.
AB  - OBJECTIVES: Audiovisual learning resources have become valuable adjuncts to
      formal teaching in surgical training. This report discusses the process and
      challenges of preparing an audiovisual teaching tool for laparoscopic
      cholecystectomy. The relative value in surgical education and training, for both
      the creator and viewer are addressed. DESIGN/SETTING: This audiovisual teaching
      resource was prepared as part of the Master of Surgery program at the University
      of Sydney, Australia. The different methods of video production used to create
      operative teaching tools are discussed. RESULTS: Collating and editing material
      for an audiovisual teaching resource can be a time-consuming and technically
      challenging process. However, quality learning resources can now be produced even
      with limited prior video editing experience. With minimal cost and suitable
      guidance to ensure clinically relevant content, most surgeons should be able to
      produce short, high-quality education videos of both open and minimally invasive
      surgery. CONCLUSIONS: Despite the challenges faced during production of
      audiovisual teaching tools, these resources are now relatively easy to produce
      using readily available software. These resources are particularly attractive to
      surgical trainees when real time operative footage is used. They serve as
      valuable adjuncts to formal teaching, particularly in the setting of minimally
      invasive surgery.

PMID- 22483145
TI  - The surgical skills laboratory residency interview: an enjoyable alternative.
AB  - PURPOSE: The authors aimed to trial an alternative interviewing strategy by
      inviting residency candidates to our surgical anatomy laboratory. Interviews were
      coincident with surgical dissection. The authors hypothesized that residency
      candidates hoping to match into a surgical subspecialty might enjoy this
      unconventional interviewing strategy, which would mimic an operating room
      experience. METHODS: On scheduled residency interview dates, formal, unstructured
      interviews were held with half of the neurosurgical faculty, and unstructured
      surgical skills laboratory-based interviews were held with the other half of the
      neurosurgical faculty. Interviews in the skills laboratory featured cases and
      corresponding surgical dissection guided by faculty. After the interview, the
      residency candidates were encouraged to complete an optional survey about their
      interview process. The survey results were pooled for analysis. RESULTS: Of 28
      interviewed, 19 individuals responded to the survey. The survey respondents had
      favorable reviews of the all aspects of the interview process. When asked to
      report the most enjoyable part of the interview, all respondents listed the
      surgical skills laboratory. The average respondent scores for importance of the
      surgical skills laboratory interview (9.5 +/- 1.1) compared with conventional
      interview with faculty (9.2 +/- 1.0) or residents (9.1 +/- 1.0) was not
      significantly different (p = 0.50, analysis of variance). CONCLUSIONS: The
      surgical skills laboratory interviews were reviewed favorably by the survey
      respondents. Nearly all respondents listed the surgical skills interview as the
      most enjoyable part of the interview experience. The authors advocate this
      residency interview strategy for surgical subspecialty residencies.

PMID- 22483146
TI  - Ultrasound-guided breast biopsy for surgical residents: evaluation of a phantom
      model.
AB  - BACKGROUND: Ultrasound is increasingly used by surgeons for evaluation of breast
      lesions. While surgical residents have sufficient exposure to breast surgery,
      many lack exposure to office-based procedures, such as ultrasound-guided breast
      biopsy. A phantom model was created to teach surgical residents basic breast
      ultrasound and biopsy skills and to evaluate the resident's response when
      incorporated into the curriculum. METHODS: The model was created using a pork
      roast and 10 variably-sized pimento olives. Twenty-four surgical residents were
      given a brief introduction to breast ultrasound followed by up to 5 minutes to
      ultrasound the model and note the embedded lesions. The number and location of
      lesions found and the time spent per resident were recorded. Residents were then
      introduced to the vacuum-assisted core biopsy system and observed performing
      ultrasound-guided biopsies. Pre- and postsession evaluations were completed by
      all residents. Scatterplot regression models were used for data analysis.
      RESULTS: Most residents had previous ultrasound instruction. The intermediate
      level residents (postgraduate year [PGY]2 and 3) found the most lesions in the
      shortest time, missing on average 1.125 lesions in 3:09 minutes. Time spent did
      not correlate with number missed or previous ultrasound experience. Over 50% of
      residents sampled the center of the lesion on their first biopsy attempt, with no
      correlation to PGY or ultrasound experience. All residents rated this experience
      good to excellent, and 67% believed their ultrasound skills were improved. Ninety
      five percent of residents felt the model was fairly realistic and 95% would like
      to have more experiences like this in the curriculum. The residents surveyed
      thought the curriculum would be best suited to a PGY2 experience. CONCLUSIONS:
      The phantom breast is a realistic and valuable teaching model for breast
      ultrasound. Further evaluation regarding skill retention is needed.

PMID- 22483147
TI  - Use of breast simulators compared with standardized patients in teaching the
      clinical breast examination to medical students.
AB  - OBJECTIVE: Simulators have replaced some standardized patients in medical student
      teaching, and their use seems to decrease anxiety related to the clinical breast
      examination (CBE). We compared learning the CBE on a breast palpation simulator
      with learning on a standardized patient with respect to skill acquisition and
      comfort level. METHODS: At Penn State College of Medicine, the class of 2008
      (historical control group, n = 113) learned the CBE on a standardized patient,
      whereas the class of 2009 (experimental group, n = 131) learned on the breast
      palpation simulator. We used measures of the process (conducting the CBE) and
      measures of the outcome (examination scores and detection of abnormal findings).
      During their third-year surgical clerkship, students in both groups completed a
      questionnaire reporting the number of CBEs performed and confidence in performing
      the CBE. The students then performed an observed examination on the simulator,
      and the number of positive findings detected was recorded. The mean number of
      positive findings was compared between groups, and an economic analysis was
      conducted. RESULTS: The experimental group had a significantly higher mean
      examination score than the historical control. In subgroups, this difference was
      significant for those who reported performing 0-5 clinical examinations but for
      not those who had performed >6 examinations. On individual items, the
      experimental group scored significantly higher in examining for neck nodes,
      nipple retraction, skin changes, and axillary evaluation. The 2 groups did not
      differ significantly in the mean number of positive findings detected or in
      ratings of comfort level. CONCLUSIONS: Medical students who learned the CBE on
      breast palpation simulators performed as well or better than those who learned on
      standardized patients; however, a subgroup analysis revealed that the benefit was
      limited to students with less clinical experience.

PMID- 22483148
TI  - Using the hidden curriculum to teach professionalism during the surgery
      clerkship.
AB  - BACKGROUND: It has been shown that medical student professionalism is influenced
      by the hidden curriculum, although the extent to which this occurs during the
      surgery clerkship is unknown. Furthermore, the processes within the hidden
      curriculum have been used to teach professionalism to medical students, but this
      strategy has not been used during the surgery clerkship. The purpose of this
      study was to review a 2-year experience with a surgery clerkship instructional
      session where the hidden curriculum was used to teach professionalism to medical
      students. STUDY DESIGN: Medical student essays were analyzed to evaluate the
      influence of the hidden curriculum on their ideas about professionalism and to
      identify specific behaviors that they regarded as professional and
      unprofessional. The instructional session was evaluated using the average
      satisfaction session ratings and through an analysis of medical student session
      evaluation comments. RESULTS: Seventy-five percent of medical students reported
      that their ideas about professionalism changed. This change involved their
      general concepts about professionalism, identifying specific behaviors that they
      planned to adopt or avoid, or developing opinions about the professionalism of
      surgeons. The average satisfaction rating was consistently high throughout the
      study period, and the most helpful session feature was reported as the
      opportunity to share and discuss their observations. CONCLUSIONS: The hidden
      curriculum has a substantial influence on the development of professionalism of
      medical students during the surgery clerkship. It was possible to illuminate and
      use the hidden curriculum to create an instructional session devoted to
      professionalism for medical students on the surgery clerkship.

PMID- 22483149
TI  - Video review using a reliable evaluation metric improves team function in high
      fidelity simulated trauma resuscitation.
AB  - OBJECTIVE: To demonstrate that instruction of proper team function can occur
      using high-fidelity simulated trauma resuscitation with video-assisted debriefing
      and that this process can be integrated rapidly into a standard general surgery
      curriculum. DESIGN: The rater reliability of our team metric was assessed by
      having physicians and nonphysicians rate the same video-recorded trauma
      simulations at intervals in time. To assess the effectiveness of video
      debriefing, subjects participated in a 3-week trauma team training course that
      consisted of 2 video-recorded simulation sessions, each approximately 2 hours in
      length separated by a 90-minute debriefing session. To assess the impact of the
      debriefing session, video recordings of participants performing resuscitations
      before and after the debriefing were reviewed by a panel of blinded
      traumatologists and graded using our team evaluation instrument. SETTING: The
      study took place at the high-fidelity simulation center at a large, urban
      academic training hospital. PARTICIPANTS: All 11 PGY-2 general surgery and
      combined general surgery and plastic surgery residents at our institution.
      RESULTS: Our instrument was found to have high interrater correlation (interclass
      correlation coefficient [ICC], 0.926; 95% confidence interval, 0.893-0.953).
      Initially, residents were either unsure as to their competency to serve as team
      leader (70%) or felt they were not competent to serve as team leader (30%).
      Ninety percent of residents found the video debriefing very to extremely helpful
      in improving team function and clinical competency. All participants felt more
      competent as both team leaders and team members because of the video debriefing.
      The mean team function score improved significantly after video debriefing (4.39
      [+/-0.3] vs 5.45 [+/-0.4] prevideo vs postvideo review, p < 0.05). CONCLUSIONS:
      Video review with debriefing is an effective means of teaching team competencies
      and improving team function in simulated trauma resuscitation. This strategy can
      be integrated readily into the surgical curriculum analogous to other
      applications of simulation technology.

PMID- 22483150
TI  - Service versus education, what are we talking about?
AB  - OBJECTIVE: To investigate the degree of variability in perception as related to
      the service versus education issue in general surgery residency education. STUDY
      DESIGN: A survey questionnaire was designed with 15 scenarios constructed by the
      author to represent an array of resident experiences with differing educational
      and noneducational value. After appropriate Institutional Review Board (IRB)
      approval, the survey was administered to a variety of medical student, resident,
      and faculty groups. Individual and intergroup variability was assessed. SETTING:
      Large, university-affiliated teaching hospital. RESULTS: A total of 137
      questionnaires were returned from medical students, residents, and attending
      physicians encompassing several medical specialties and a broad range of clinical
      experience. In all, 7 of 15 scenarios resulted in statistically significant
      different response patterns across specialties and 8 of 15 scenarios across
      levels of experience. Individual responses spanned nearly all possible responses
      for most scenarios. CONCLUSIONS: Considerable variability exists across
      individuals as well as groups in the interpretation of the types of experiences
      that represent service, education, or both in general surgery residency training.
      Arriving at a quantifiable balance in service versus education in general surgery
      resident education may never be possible given the variability in interpretation
      of the various activities residents perform. This must be kept in mind in both
      interpreting the results of the Accreditation Council for Graduate Medical
      Education (ACGME) survey and also when designing educational activities within a
      program.

PMID- 22483151
TI  - Speaking from the heart: end-of-life discussions in the ICU from the surgeon's
      perspective.

PMID- 22483152
TI  - Editorial : novel and emerging drugs for leukemias.
AB  - For the last twenty years, significant progress in molecular and cellular biology
      has resulted in a better characterization and understanding of the molecular
      abnormalities in leukemias. These achievements have provided new opportunities
      for the development of innovative, more effective drugs. Novel therapies are
      being evaluated both in preclinical studies and in early clinical trials. In this
      editorial, we demonstrate a brief review of the present insights into new
      therapeutic strategies for acute and chronic leukemias.

PMID- 22483154
TI  - Emerging therapies in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) therapy has dramatically changed in the last
      decade due to the introduction of tyrosine kinase inhibitors (TKIs) - imatinib,
      nilotinib and dasatinib. Despite the significant prolongation of overall survival
      of CML patients there is still room for improvement. Approximately 20-25% of
      patients initially treated with imatinib will need alternative therapy, due to
      drug resistance which is often caused by the appearance of clones expressing
      mutant forms of BCR-ABL. Second generation TKIs dasatinib and nilotinib have
      shown promising results in imatinibresistant or intolerant CML patients, but are
      not active against CML clones with highly resistant T315I mutation. In recent
      years special attention is placed on small pool of leukemic stem cells which may
      contribute to the persistence of the leukemia. This article provides a review of
      preclinical and clinical data concerning the most promising new directions in CML
      treatment, with special emphasis on new drugs active in T315I mutation and
      compounds affecting leukemic stem cells.

PMID- 22483153
TI  - Novel and emerging drugs for acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a challenging disease to treat with the majority
      of patients dying from their illness. While overall survival has been markedly
      prolonged in acute promyelocytic leukemia (APL), survival in younger adults with
      other subtypes of AML has only modestly improved over the last twenty years.
      Physicians who treat AML eagerly await drugs like Imatinib for chronic myeloid
      leukemia, Cladribine for hairy cell leukemia, and Rituximab for non-Hodgkin
      Lymphoma which have had an important impact on improving outcome. Recent research
      efforts have focused on refining traditional chemotherapeutic agents to make them
      more active in AML, targeting specific genetic mutations in myeloid leukemia
      cells, and utilizing novel agents such as Lenalidomide that have shown activity
      in other hematologic malignancies. Here, we focus on reviewing the recent
      literature on agents that may assume a role in clinical practice for patients
      with AML over the next five years.

PMID- 22483155
TI  - Novel and emerging drugs for rarer chronic lymphoid leukaemias.
AB  - Rarer chronic lymphoid leukaemias represent a challenge to the clinicians due to
      the limited information on their pathogenesis, difficulties on setting up
      prospective clinical trials and to their refractoriness to drugs used in the most
      common form of chronic lymphocytic leukaemia (CLL). In this review all these
      issues are addressed in three B-cell leukaemias: B-cell prolymphocytic leukaemia
      (B-PLL), hairy cell leukaemia (HCL) and HCL-variant and three T-cell leukaemias:
      T-cell prolymphocytic leukaemia (T-PLL), T-cell large granular lymphocytic
      leukaemia (T-cell LGLL) and adult T-cell leukaemia lymphoma (ATLL). Data will be
      presented on the natural history, current therapies and emerging drugs
      potentially useful in the treatment of patients with these leukaemias. Emphasis
      is made on: 1- the novel agents targeting a variety of B and T-cell antigens
      expressed on the surface of the leukaemic cells; these are either unconjugated
      monoclonal antibodies (McAb) such as Rituximab (anti-CD20), the second and third
      generation of anti-CD20 McAbs, Alemtuzumab (anti-CD52), Siplizumab (anti-CD2),
      Daclizumab (anti-CD25) and KW-0761, an anti-chemokine receptor 4 (CCR4) or McAbs
      conjugated to toxins such as CD22 linked to the pseudomonas exotoxin or
      radiolabelled McAb; 2- the use of new purine nucleosides such as nelarabine and 3
      agents targeting deregulated genes in the leukaemic cells from these diseases
      such as the Poly (ADP-ribose) polymerase (PARP) Olarapib in T-PLL with
      deregulation of the ataxia telangiectasia mutated (ATM) gene. Data of phase I and
      II clinical studies with these agents as well as the potential and current use of
      other drugs are outlined.

PMID- 22483156
TI  - Novel and emerging drugs for acute lymphoblastic leukemia.
AB  - Over the past several decades the important progress has been made in the
      management of acute lymphoblastic leukemia (ALL), especially among children.
      However, in adult patients reported cure rates seldom exceeded 40%, despite the
      use of hematopoietic stem-cell transplantation in many cases. Conventional
      chemotherapy is toxic and ineffective. Therefore, new treatment options and risk
      adapted therapies are needed to improve the outcome of ALL patients. This review
      is focused on new systemic treatment modalities, such as nucleoside analogues,
      purine synthetase inhibitors, monoclonal antibodies, tyrosine kinase inhibitors
      and other agents targeting molecular pathways that are aimed to benefit patients
      and improve the outcome of their treatment.

PMID- 22483157
TI  - Temporary quadriplegia following continuous thoracic paravertebral block.
AB  - A case of temporary quadriplegia following a continuous thoracic paravertebral
      block in an adult patient scheduled for video-assisted thoracoscopy is presented.
      An 18-gauge Tuohy needle was inserted under direct vision by the surgeon but the
      tip of the catheter was not localized. Postoperatively, the patient developed
      temporary quadriplegia 90 minutes after the start of a continuous infusion of
      ropivacaine 0.2%. Imaging studies showed that the catheter was localized in the
      intrathecal space.

PMID- 22483158
TI  - Integrated programs for mothers with substance abuse issues and their children: a
      systematic review of studies reporting on child outcomes.
AB  - BACKGROUND: Integrated treatment programs (those that include on-site pregnancy-,
      parenting-, or child-related services with addiction services) were developed to
      break the intergenerational cycle of addiction, potential child maltreatment, and
      poor outcomes for children. OBJECTIVES: To examine the impact and effects of
      integrated programs for women with substance abuse issues and their children, we
      performed a systematic review of studies published from 1990 to 2011. METHODS:
      Literature search strategies included online bibliographic database searches,
      checking printed sources, and requests to researchers. Studies were included if
      all participants were mothers with substance abuse problems at baseline; the
      treatment program included at least 1 specific substance use treatment and at
      least 1 parenting or child treatment service; the study design was randomized,
      quasi-experimental, or cohort; and there were quantitative data on child
      outcomes. We summarized data on child development, growth, and emotional and
      behavioral outcomes. RESULTS: Thirteen studies (2 randomized trials, 3 quasi
      experimental studies, 8 cohort studies; N=775 children) were included in the
      review. Most studies using pre-post design indicated improvements in child
      development (with small to large effects, ds=0.007-1.132) and emotional and
      behavioral functioning (with most available effect sizes being large, ds=0.652
      1.132). Comparison group studies revealed higher scores for infants of women in
      integrated programs than those not in treatment, with regard to development and
      most growth parameters (length, weight, and head circumference; with all
      available effect sizes being large, ds=1.16-2.48). In studies comparing
      integrated to non-integrated programs, most improvements in emotional and
      behavioral functioning favored integrated programs and, where available, most
      effect sizes indicated that this advantage was small (ds=0.22-0.45). CONCLUSIONS:
      Available evidence supports integrated programs, as findings suggest that they
      are associated with improvements in child development, growth, and emotional and
      behavioral functioning. More research is required comparing integrated to non
      integrated programs. This review highlights the need for improved methodology,
      study quality, and reporting to improve our understanding of how best to meet the
      needs of children of women with substance abuse issues.

PMID- 22483159
TI  - Drawing in nursing PBL.
AB  - The implementation of art education in nursing is said to have positive effects
      on nursing students. Most studies applied visual art dialogues or object design,
      whereas the effectiveness of drawing as a teaching and learning method is rarely
      examined and discussed. This paper aimed to discuss the potential and
      effectiveness of drawing as a learning and teaching method. Four drawings which
      were created by Hong Kong nursing students are demonstrated and the students'
      perspectives of how drawing enhanced learning are shown in this paper. Topics on
      drawing as a fun teaching and learning method and the way it can enhance critical
      thinking and creativity are also discussed. In conclusion, the activity was a
      great success, and students enjoyed the learning process and reflected positive
      comments. However, we cannot conclude that drawing is an effective teaching and
      learning method based on a single paper, therefore more similar studies should be
      conducted to investigate this method. 

PMID- 22483160
TI  - "What made me stay?" A review of the reasons student nurses enrolled in a
      Bachelor of Nursing programme completed their studies: a descriptive
      phenomenological study.
AB  - Schools of nursing in New Zealand are now being asked for data on retention and
      completition rates for inclusion within their Tertiary Institution's performance.
      A continuing issue facing Schools of Nursing in their Bachelor of Nursing degree
      level studies are the struggles that some students face during their studies.
      Some overcome these difficulties and may complete the programme within the three
      year plan of study. Others take up to the five years allowed by the Nursing
      Council of New Zealand. This study, using a qualitative phenomenological research
      methodology, aimed to determine common themes that emerged as to why students
      stayed and completed their programme of study to become a Registered Nurse. The
      initial thematic analysis indicated that the greatest reason that students stayed
      related to the broad theme of "support". There were secondary themes under this
      related to family, friends and peers, and the tutorial staff. A second broad
      determinant of the decision to stay and complete their study related to the
      impact of financial costs on themselves and their families. Although support from
      family, friends, peers, and the education provider were important, participants
      stated that their goal setting and desire to achieve were critical to their
      completition of the programme. For us in the Faculty we believe that a major
      indicated theme is that we need to be more involved in the pastoral care of our
      students.

PMID- 22483161
TI  - Improving nursing students' knowledge using online education and simulation to
      help smokers quit.
AB  - The purpose of this study was to examine an evidence-based smoking cessation
      education program effect on nursing students' perceptions and self-confidence to
      help smokers quit smoking. METHOD: Upon completion of an on-line educational
      program students were provided opportunities to practice through simulation. Data
      were collected by pre and post assessment tools for the online-education and by a
      post assessment tool for the simulation. RESULTS: 110 senior nursing students
      participated in this study. Students' confidence in their overall ability to
      assist smokers to quit smoking was statistically significant compared to baseline
      (t=4.09, p<.001). Students self-rated higher levels of smoking cessation skills
      on Advising, Assessing, Assisting, and Arranging compared to baseline (p<0.00).
      CONCLUSION: Integration of evidence-based didactic and practical smoking
      cessation program into curricula improves nursing students' clinical skills in
      helping smokers to quit.

PMID- 22483162
TI  - A randomized controlled trial of allopurinol vs. placebo added on to
      antipsychotics in patients with schizophrenia or schizoaffective disorder.
AB  - Adenosine agonists produce behavioral effects similar to dopamine antagonists,
      hence increasing adenosine levels might improve symptoms of schizophrenia. This
      hypothesis is supported by three single-site studies indicating that allopurinol,
      which increases adenosine levels, improved symptoms in patients with
      schizophrenia. We performed a multi-center, 8-week RCT of allopurinol vs. placebo
      added to anti-psychotic medications in 248 patients with schizophrenia or
      schizoaffective disorder. Both groups showed improvement in the PANSS (effect
      size 1.13) and in clinical and cognitive measures. No difference was observed
      between groups in primary (t=0.01, p=0.992) or secondary outcome measures. These
      findings do not support allopurinol as a treatment for schizophrenia.

PMID- 22483163
TI  - Commentary on the new American Geriatric Society Beers criteria for potentially
      inappropriate medication use in older adults.

PMID- 22483164
TI  - Chromium picolinate and chromium histidinate protects against renal dysfunction
      by modulation of NF-kappaB pathway in high-fat diet fed and Streptozotocin
      induced diabetic rats.
AB  - BACKGROUND: Diabetic nephropathy is one of major complications of diabetes
      mellitus. Although chromium is an essential element for carbohydrate and lipid
      metabolism, its effects on diabetic nephropathy are not well understood. The
      present study was conducted to investigate the effects of chromium picolinate
      (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-kappaB)
      and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney. METHODS:
      Male Wistar rats were divided into six groups. Group I received a standard diet
      (8% fat) and served as a control; Group II was fed with a standard diet and
      received CrPic; Group III was fed with a standard diet and received CrHis; Group
      IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected
      with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ)
      but supplemented with CrPic for 12 weeks. Group VI was treated as group IV
      (HFD/STZ) but supplemented with CrHis. RESULTS: The increased NF-kappabeta p65 in
      the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In
      STZ-treated rats, a significant decrease in levels of nuclear factor of kappa
      light polypeptide gene enhancer in B-cells inhibitor, alpha (IkappaBalpha) was
      found in kidney tissues when compared to control rats (P < 0.05). A significant
      increase in the levels of IkappaBalpha was observed in CrPic- and CrHis-treated
      rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly
      decreased in diabetic rats compared with the control rats. There was a higher
      tendency for increase of kidney Nrf2 level and decrease in kidney NFkappaBp65
      levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic
      rats. CONCLUSION: Our result show that in kidney tissue CrHis/CrPic increases
      Nrf2 level, parallelly decreases NF-kappaB and partially restores IkappaBalpha
      levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in
      antioxidant defense system via the Nrf2 pathway by reducing inflammation through
      NF-kappabeta p65 inhibition. Moreover, a greater reduction in NF-kappaB
      expression and greater increases in expressions of IkappaBalpha and Nrf2 in
      diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest
      that CrHis has more favorable effects than CrPic.

PMID- 22483165
TI  - Bilateral Epstein-Barr virus-associated adrenal leiomyomas in a child without an
      established immunodeficiency.
AB  - Adrenal leiomyomas are rare, bilateral ones being rarer. Literature available on
      these rare tumors documents only 4 cases in children less than 12 years of age.
      Each case has been associated with acquired immune deficiency syndrome or some
      other immunodeficiency state. Here we present a rare case of large, bilateral,
      adrenal leiomyomas in a child with no known immunodeficiency. An 11-year-old girl
      with a past history of herpes zoster (1 year before the present complaints) was
      admitted with abdominal pain of 2 months' duration. Radiology revealed bilateral
      adrenal neoplasms, probably bilateral pheochromocytoma. Histology showed
      bilateral adrenal leiomyomas that were Epstein-Barr virus associated. We report
      this case to draw attention to the occurrence of a common pathologic entity at an
      uncommon site in a setting of no definite known immunodeficiency.

PMID- 22483166
TI  - Benefits from intracoronary as compared to intravenous abciximab administration
      for STEMI patients undergoing primary angioplasty: a meta-analysis of 8
      randomized trials.
AB  - BACKGROUND: Adjunctive abciximab administration has been demonstrated to reduce
      mortality and reinfarction in patients with ST-elevation myocardial infarction
      (STEMI) referred to invasive management. Standard abciximab regimen consists of
      an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies
      and small clinical trials suggest the superiority of intracoronary (IC) injection
      of abciximab over IV route. Therefore, the aim of the current study was to
      perform a meta-analysis of randomized trials (RCTs) to assess the clinical
      efficacy and safety of IC vs IV abciximab administration in STEMI patients
      undergoing primary angioplasty. METHODS: We obtained results from all RCTs
      enrolling STEMI patients undergoing primary percutaneous coronary intervention
      (PCI). The primary endpoint was mortality, while recurrent myocardial infarction,
      postprocedural epicardial (TIMI 3) and myocardial (MBG 2-3) perfusion were
      identified as secondary endpoints. The safety endpoint was the risk of major
      bleeding complications. RESULTS: A total of 8 randomized trials were finally
      included in the meta-analysis, enrolling a total of 3259 patients. As compared to
      IV route, IC abciximab was associated with a significant improvement in
      myocardial perfusion (OR [95% CI]=1.76 [1.28-2.42], p<0.001), without significant
      benefits in terms of mortality (OR [95% CI]=0.85 [0.59-1.23], p=0.39),
      reinfarction (OR [95% CI]=0.79 [0.46-1.33], p=0.37), or major bleeding
      complications (OR [95% CI]=1.19 [0.76-1.87], p=0.44). However, we observed a
      significant relationship between patient's risk profile and mortality benefits
      from IC abciximab administration (p=0.011). CONCLUSIONS: The present updated meta
      analysis showed that IC administration of abciximab is associated with
      significant benefits in myocardial perfusion, but not in clinical outcome at
      short-term follow-up as compared to IV abciximab administration, without any
      excess of major bleedings in STEMI patients undergoing primary PCI. However, a
      significant relationship was observed between patient's risk profile and
      mortality benefits from IC abciximab administration. Therefore, waiting for long
      term follow-up results and additional randomized trials, IC abciximab
      administration cannot be routinely recommended, but may be considered in high
      risk patients.

PMID- 22483167
TI  - Axillary ultrasound examination is useful for selecting patients optimally suited
      for sentinel lymph node biopsy after primary systemic chemotherapy.
AB  - BACKGROUND: Controversy surrounds the reliability of sentinel lymph node biopsy
      after primary systemic chemotherapy. In this study, we assessed axillary
      ultrasound for selecting patients most likely to optimally benefit from biopsy.
      METHODS: The study included 87 patients who received primary systemic
      chemotherapy and underwent a sentinel lymph node biopsy followed by axillary
      lymph node dissection. Lymph nodes >10 mm in diameter, irregularly swollen,
      round, and homogeneously hypoechoic without an echo-rich center were considered
      axillary ultrasound positive. RESULTS: In axillary ultrasound-negative patients
      before and after primary systemic chemotherapy, identification, sensitivity, and
      false-negative rates were 81%, 100%, and 0%, respectively. However, in patients
      whose lymph nodes converted from positive to negative after primary systemic
      chemotherapy, these values were 83%, 70.8%, and 29.2%, respectively. CONCLUSIONS:
      Axillary ultrasound-negative patients before and after primary systemic
      chemotherapy were suitable for sentinel lymph node biopsy. Axillary ultrasound
      should be used during primary systemic chemotherapy and before surgery.

PMID- 22483168
TI  - Substituent effects on the thermochemistry of thiophenes. a theoretical
      (G3(MP2)//B3LYP and G3) study.
AB  - Very good linear correlations between experimental and calculated enthalpies of
      formation in the gas phase (G3(MP2)//B3LYP and G3) for 48 thiophene derivatives
      have been obtained. These correlations permit a correction of the calculated
      enthalpies of formation in order to estimate more reliable "experimental" values
      for the enthalpies of formation of substituted thiophenes, check the reliability
      of experimental measurements, and also predict the enthalpies of formation of new
      thiophenes that are not available in the literature. Moreover, the difference
      between the enthalpies of formation of isomeric thiophenes with the same
      substituent in positions 2 and 3 of the ring has been analyzed. Likewise, a
      comparison of the substituent effect in the thiophene and benzene rings has been
      established.

PMID- 22483169
TI  - New wine in old bottles: expanding roles for B cells in transplantation
      tolerance.

PMID- 22483170
TI  - Worker honeybee sterility: a proteomic analysis of suppressed ovary activation.
AB  - Eusocial behavior is extensively studied in the honeybee, Apis mellifera, as it
      displays an extreme form of altruism. Honeybee workers are generally obligatory
      sterile in a bee colony headed by a queen, but the inhibition of ovary activation
      is lifted upon the absence of queen and larvae. Worker bees are then able to
      develop mature, viable eggs. The detailed repressive physiological mechanisms
      that are responsible for this remarkable phenomenon are as of yet largely
      unknown. Physiological studies today mainly focus on the transcriptome, while the
      proteome stays rather unexplored. Here, we present a quantitative 2-dimensional
      differential gel electrophoresis comparison between activated and inactivated
      worker ovaries and brains of reproductive and sterile worker bees, including a
      spot map of ovaries, containing 197 identified spots. Our findings suggest that
      suppression of ovary activation might involve a constant interplay between
      primordial oogenesis and subsequent degradation, which is probably mediated
      through steroid and neuropeptide hormone signaling. Additionally, the observation
      of higher viral protein loads in both the brains and ovaries of sterile workers
      is particularly noteworthy. This data set will be of great value for future
      research unraveling the physiological mechanisms underlying the altruistic
      sterility in honeybee workers.

PMID- 22483171
TI  - Sensing of 2 atrial rhythms by a pacemaker in a transplanted heart.
AB  - A patient who had undergone orthotopic heart transplantation received a VDD
      pacemaker for AV block. The pacemaker sensed both the recipient and donor atrial
      rhythms. The atrial lead must be implanted in the donor atrium: a double atrial
      electrogram requires a different atrial site unless programmable atrial
      sensitivity can establish preferential sensing of donor P waves.

PMID- 22483172
TI  - Systematic reviews of the literature on clipping and coiling of unruptured
      intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: The best management of unruptured aneurysms remains
      controversial. Accurate estimates of treatment-related morbidity and efficacy are
      needed for clinical decision making. METHODS: We review recent systematic
      reviews, case series and population-based studies on clipping and coiling of
      unruptured aneurysms. A critical analysis of the quality of available studies and
      of the reliability of results is followed by reappraisal of the logic of clinical
      research on unruptured aneurysms. RESULTS: Unfavourable outcome, including death,
      up to 1 year after surgical clipping, was found in 692 of 9845 patients (REW
      average: 6.7%; (99%)CI: 4.9-9.0). Unfavourable outcome after coiling occurred in
      189 of 5044 patients (REW average 4.8%, ((99%)CI: 3.9-6.0). Location and size of
      aneurysms were risk factors for clipping, while no risk factor reached
      statistical significance for coiling studies. The quality of reports was in
      general poor. Estimates from epidemiological studies showed higher morbidity
      rates than reviews of case series. Treatment efficacy could not be assessed. All
      studies are attempts to provide answers to questions that were never properly
      raised. CONCLUSION: Results of reviews and observational studies should serve as
      hypotheses for clinical trials.

PMID- 22483173
TI  - How to choose clipping versus coiling in treating intracranial aneurysms.
AB  - BACKGROUND: After the decision is made to treat an intracranial aneurysm,
      clinicians must choose between two competing treatment options; open surgery or
      endovascular therapy. The rationale underlying the choice of treatment modality
      is usually unclear, as there is little good quality evidence available. METHODS:
      We discuss the patient and aneurysm-related factors cited in the neurovascular
      literature that are considered to influence aneurysm treatment choices. RESULTS:
      The relevance and direction of influence of rupture status, age, type of
      presentation, and general medical condition, as well as aneurysm size, location,
      morphology, and multiplicity are discussed. The validity of these factors in
      influencing treatment decisions remains unclear, with frequently opposing views
      on the same factor by clinicians practicing opposing techniques. Perceived
      differences in efficacy and safety of the two different treatment approaches are
      commonly used in an attempt to justify treatment choices. Difficulties with
      treatment selection and case-by-case reasoning are reviewed. CONCLUSION: Properly
      designed and conducted randomized trials are necessary in order to settle the
      controversy and to determine the optimal treatment modality for intracranial
      aneurysms. In the absence of reliable knowledge on which to base treatment
      decisions, the ethically appropriate choice for any clinician, from surgical or
      endovascular backgrounds, is to participate in randomized trials.

PMID- 22483175
TI  - Major upper-limb amputations for malignant tumors.
AB  - PURPOSE: With the continued advancement of limb salvage surgery, major upper-limb
      amputations are being performed less frequently and are generally reserved for
      patients with large, multifocal, or recurrent tumors for whom limb salvage is no
      longer an option. We conducted a retrospective review of the current indications
      and patient outcomes after major upper-limb amputations for malignant tumors.
      METHODS: Using the institution surgical database, we identified 43 patients who
      underwent major upper-limb amputation for primary and metastatic malignant tumors
      from 1996 to 2008. RESULTS: Of these 43 patients, 25 had soft tissue sarcoma, 7
      had bone sarcoma, and 11 had carcinoma. Two patients had stage I, 3 had stage II,
      21 had stage III, and 17 had stage IV disease. We performed 45 amputations: 5
      below the elbow, 14 above the elbow, and 26 at the forequarter. Among the 45
      amputations, 2 patients underwent a second more proximal amputation for local
      tumor recurrence. Of the 17 patients with stage IV disease, 10 underwent
      palliative amputation for symptom control. A total of 28 patients (65%) died.
      Median survival after amputation was 13 months (95% confidence interval, 8-19
      mo). The 6-month cumulative incidence of local recurrence was 22%. Overall
      survival after forequarter amputations was 42% at 1 year. CONCLUSIONS: Survival
      after major upper-limb amputation is poor, especially because amputations are
      reserved for patients with advanced tumors. However, amputation remains an option
      for local tumor control and can palliate symptoms in selected patients.
      Improvement of survival requires more effective systemic treatment strategies.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 22483177
TI  - Vascularized bone grafts for scaphoid nonunions.
AB  - Scaphoid fractures that fail to unite are at risk of developing avascular
      necrosis and progressive structural collapse, thereby complicating attempts at
      revision surgical treatment. Vascularized bone grafts have demonstrated utility
      in promoting consolidation in the treatment of scaphoid nonunions complicated by
      avascular necrosis. Numerous pedicled and free vascularized grafts have been
      described with variable, but generally favorable, outcomes. Understanding the
      indications for different grafts is critical to the successful application of
      these techniques and grafts in the treatment of challenging scaphoid nonunions.

PMID- 22483176
TI  - Nonoperative treatment of digital ischemia in systemic sclerosis.

PMID- 22483178
TI  - Posterior elbow release and humeral osteotomy for patients with arthrogryposis.
AB  - Children with arthrogryposis often lack the ability to feed themselves, largely
      due to limited shoulder external rotation and elbow flexion. Patients who can
      achieve passive elbow flexion through a surgical release but who cannot
      externally rotate their shoulders are still unable to reach their mouths with
      their hands. Combining a posterior elbow capsular release with a simultaneous
      humeral osteotomy in these patients places the forearm and hand in a much better
      position for function with minimal additional surgical exposure.

PMID- 22483179
TI  - Biomechanical measurements of forearm pronosupination with common methods of
      immobilization.
AB  - PURPOSE: To define the pronosupination arc for various types of forearm
      immobilization. We hypothesized that these methods of immobilization offer
      control of forearm pronosupination proportional to the loss of elbow motion, and
      that the Muenster cast may offer the most practical method of limiting forearm
      motion without eliminating elbow motion. METHODS: We enrolled 15 subjects in the
      study. We took measurements using computerized biometrics with the elbow free of
      immobilization and in a long-arm cast, a Muenster cast, a removable splint set to
      90 degrees  elbow flexion, and a splint set to allow elbow flexion permissible by
      the Muenster cast. We recorded measurements for pronation and supination arcs.
      RESULTS: We obtained average pronosupination arcs for the unrestricted elbow (189
      degrees ), long arm cast (11 degrees ), Muenster cast (35 degrees ), removable
      splint set to 90 degrees  (124 degrees ), and splint set to the flexion-extension
      arc of the Muenster cast (139 degrees ). We found statistically significant
      differences for pronation and supination for all comparisons between
      immobilization methods, with the exception of the splints compared with each
      other. The least motion was found in the long-arm cast, whereas the Muenster cast
      offered the only option allowing minimal pronosupination without strict elbow
      immobilization. CONCLUSIONS: The Muenster cast offers reasonable immobilization
      of the forearm without fully immobilizing the elbow. The long-arm cast option
      offers significantly more forearm stability at the cost of any elbow motion. The
      2 splints tested do not effectively immobilize the forearm compared with the
      other modalities tested. CLINICAL RELEVANCE: This study provides good
      biomechanical support for using a Muenster cast when limiting forearm rotation is
      desirable.

PMID- 22483180
TI  - Extra-articular fractures of the proximal phalanges of the fingers: a comparison
      of 2 methods of functional, conservative treatment.
AB  - PURPOSE: For nonsurgical treatment of fractures of the proximal phalanges of the
      triphalangeal fingers, different dynamic casts have been described. The main
      principle behind these casts is advancement and tightening of the extensor hood,
      caused by a combination of blocking the metacarpophalangeal joints in flexion and
      actively flexing the proximal interphalangeal joints. In contrast to established
      treatment protocols using functional forearm casts, the Lucerne cast allows for
      free mobilization of the wrist joint. The purpose of the current multicenter
      study was to compare the results of conservative, functional treatment using 2
      different methods, either a forearm cast or a Lucerne cast. METHODS: Over a 2
      year-period, a prospective, randomized, multicenter study was conducted at 4
      hospitals in Switzerland. Clinical and radiological results of 66 consecutive
      patients having 75 extra-articular fractures of the proximal phalanges were
      recorded through a minimum follow-up of 3 months. Intra-articular and physeal
      fractures, pathological fractures, open fractures, concomitant injuries of the
      tendons or collateral ligaments, and accidents more than 7 days before
      presentation were excluded from the study. RESULTS: Radiographically, there were
      no statistically significant differences between the 2 groups in terms of palmar
      apex angulation and radial or ulnar angulation. There were no differences in
      total active range of finger motion. Wrist joint motion at the time of cast
      removal was statistically superior in patients treated with Lucerne cast.
      However, there were no significant differences in wrist joint motion at 12 weeks
      of follow-up. CONCLUSIONS: The clinical and radiological results achieved with
      the Lucerne cast are comparable to those of established treatment. Well-reduced,
      minimally angulated, or nonangulated fractures of the proximal phalanges of the
      fingers can be effectively treated using functional casts without immobilizing
      the wrist. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

PMID- 22483181
TI  - Cutaneous angiosome territory of the medial femoral condyle osteocutaneous flap.
AB  - PURPOSE: The medial femoral condyle flap is used for treatment of nonunions with
      or without intercalary bone loss. Most reported uses have been without a skin
      segment, but this flap can provide a skin component supplied by the saphenous
      artery branch (SAB) of the descending genicular artery (DGA) pedicle. Experience
      with this flap suggests that an additional distinct, reliable, more-distal, DGA
      cutaneous branch can be found at condyle level, capable of supporting skin
      without using the SAB. This cadaver study evaluated SAB and DGA-cutaneous branch
      angiosome territories. A clinical case series assesses the DGA-cutaneous branch's
      clinical utility. METHODS: The DGA and SAB were isolated in 12 cadaveric legs,
      divided, and separately cannulated. Red dye and methylene blue were selectively
      injected into each vessel manually. Skin perfusion was measured and photographed.
      RESULTS: In all specimens, the DGA was present, originating 14.2 cm proximal to
      the joint line, and demonstrated a distinct cutaneous branch at condyle level.
      This vessel provided an average perfusion area of 70 cm(2), centered over the
      medial knee. The SAB was identified in 11 specimens (92%), with an average
      perfusion area of 361 cm(2) along the medial aspect of the distal thigh and
      proximal leg. The DGA communicating branch was present and used for perfusion of
      the skin paddle in 17 of 20 cases. The SAB was present in 18 of 20 cases, used
      with DGA-communicating branch in 4 cases, and the sole source of skin perfusion
      in 1 case. In 2 remaining cases, neither the SAB nor DGA communicating branch was
      adequate for perfusion of a skin segment. CONCLUSIONS: The medial femoral condyle
      flap can be harvested with a large skin paddle based on the SAB. A smaller skin
      segment can be harvested using the more distal DGA-communicating branch at
      condyle level. CLINICAL RELEVANCE: Improved understanding of the skin island
      associated with the DGA's saphenous and cutaneous branches can provide a rapid,
      reliable method of skin-segment harvest.

PMID- 22483182
TI  - Alternative medicine in periodontal therapy--a review.
AB  - Periodontal diseases continue to be most commonly occurring oral diseases in
      modern times. Many therapeutic modalities have been tried and tested to relieve
      these problems. The conventional therapy--scaling and root planing (SRP)--stands
      out to be the most used mode of treatment, and other treatments remain applicable
      as adjuncts to SRP, including acupuncture, acupressure, and aromatherapy. The
      present article discusses the applications of the abovementioned therapeutic
      modes and their relevance in current scenarios. Alternative medicine may be
      preferred as an adjunct to conventional periodontal therapy to relieve pain, bad
      breath, gingival inflammation, mouth ulcers, and mouth sores.

PMID- 22483183
TI  - Effects of trigger point acupuncture treatment on temporomandibular disorders: a
      preliminary randomized clinical trial.
AB  - We compared the effects of trigger point acupuncture with that of sham
      acupuncture treatments on pain and oral function in patients with
      temporomandibular disorders (TMDs). This 10-week study included 16 volunteers
      from an acupuncture school with complaints of chronic temporomandibular joint
      myofascial pain for at least 6 months. The participants were randomized to one of
      two groups, each receiving five acupuncture treatment sessions. The trigger point
      acupuncture group received treatment at trigger points for the same muscle, while
      the other acupuncture group received sham treatment on the trigger points.
      Outcome measures were pain intensity (visual analogue scale) and oral function
      (maximal mouth opening). After treatment, pain intensity was less in the trigger
      point acupuncture group than in the sham treatment group, but oral function
      remained unchanged in both groups. Pain intensity decreased significantly between
      pretreatment and 5 weeks after trigger point (p<0.001) and sham acupunctures
      (p<0.050). Group comparison using the area under the curve demonstrated a
      significant difference between groups (p=0.0152). Compared with sham acupuncture
      therapy, trigger point acupuncture therapy may be more effective for chronic
      temporomandibular joint myofascial pain.

PMID- 22483184
TI  - Effectiveness of electroacupuncture at Zusanli (ST36) on the immunohistochemical
      density of enteroendocrine cells related to gastrointestinal function.
AB  - The purpose of this study was to examine the effects of electroacupuncture at
      Zusanli on the immunohistochemical density of enteroendocrine cells related to
      gastrointestinal function. The authors investigated the histochemical changes of
      mucous substances and immunohistochemical density of gastrin, serotonin,
      calcitonin gene-related peptide (CGRP), insulin, and pancreatic polypeptide (PP)
      secreting cells in rats. Staining density of mucous substances and the
      enteroendocrine cells of the gastrointestinal tract was observed with
      histochemical and immunohistochemical methods. Stainless steel needles with a
      diameter of 0.25 mm were inserted into Zusanli (St36, 5mm below the head of the
      fibula under the knee joint, and 2mm lateral to the anterior tubercle of the
      tibia) and connected to an electrical stimulator. The electroacupuncture (EA)
      stimulation was delivered for 30 minutes at 10 mA, 2 Hz in EA stimulation (2EA
      group) or 4 Hz in EA stimulation (4EA group) in each experimental group. In 4EA
      stimulation at the Zusanli, staining density of Alcian blue-periodic acid-Schiff
      on mucous substances of the stomach body was stronger than those of the 2EA and
      control groups. Periodic acid-Schiff staining density of pyloric mucosa in the
      4EA group was stronger than that of the 2EA and control groups. The
      immunohistochemical staining density of gastrin, serotonin, and CGRP-secreting
      cells of pylorus in the 2EA and 4EA groups was stronger than that of the control
      group. Immunohistochemical staining density of insulin and PP secreting cells of
      islets of the pancreas in the 2EA and 4EA groups was stronger than that of the
      control group. These results suggest that EA stimulus at St36 has the potential
      to influence gastric mucous substances and enteroendocrine cells (gastrin,
      serotonin, CGRP, insulin, and PP) that subsequently modulate digestive functions.

PMID- 22483185
TI  - The effect of herb-partition moxibustion on Toll-like receptor 4 in rabbit aorta
      during atherosclerosis.
AB  - OBJECTIVE: To explore the mechanism of Toll-like receptor (TLR4) inhibition in
      the delay of formation of atherosclerosis by herb-partition moxibustion. METHOD:
      Seventy-five rabbits were randomly assigned to one of five groups: blank,
      atherosclerosis (AS) model, direct moxibustion, herb-partition moxibustion, and
      drug treatment. With the exception of the blank group, all rabbits were given a
      high-fat diet in addition to immunologic injury to create the AS model. The
      experiments were carried out for 16 weeks, at which time the aorta was removed
      from each rabbit. Immunohistochemical methods were used to detect the gray level
      of the aortic TLR4 to observe the immunologic competence of its antigens.
      Fluorescent quantitative polymerase chain reaction was used to detect the
      expression of TLR4 messenger RNA (mRNA) in the aorta. RESULTS: The gray-scale
      value of TLR4 and the TLR4 mRNA expression significantly decreased (p<0.05) in
      the direct moxibustion, herb-partition moxibustion, and drug treatment groups.
      Furthermore, the effects of the herb-partition moxibustion and drug treatment
      were superior to those of the direct moxibustion. CONCLUSION: Herb-partition
      moxibustion inhibits aortic TLR4 activity and mRNA expression, showing that herb
      partition moxibustion delays the formation of atherosclerosis through the
      inhibition of TLR4 expression.

PMID- 22483186
TI  - Antiulcer potential of the ethanolic extract of Aerva persica Merrill root in
      rats.
AB  - The ethanol extract of the roots of Aerva persica (Burm f) Merrill
      (Amaranthaceae) was investigated to determine its antiulcer and in vivo
      antioxidant activities in albino Wistar rats. Ulcers were induced by ethanol and
      pylorus ligation. The extract was administered at the dose of 200mg/kg orally,
      p.o. for 15 consecutive days. The ulcer index of the ethanol extract was found to
      be significantly reduced compared with control animals. The effect was also
      assessed by determining the free acidity, pepsin activity, total carbohydrate
      (TC), and protein content (PK) in control, standard, and test group animals. The
      in vivo antioxidant activity was evaluated by determining the reduced glutathione
      level (GSH) and malondialdehyde (MDA) level in the tissue homogenates. The
      results reveal the significant reduction in the level of malondialdehyde and the
      increase in the level of reduced glutathione in the rats that received the
      ethanolic extract. Furthermore, histopathological studies have shown that
      pretreatment with the ethanolic extract of the roots of A persica reduces (100%)
      ethanol- and pylorus ligation-induced hemorrhagic necrosis in rats.

PMID- 22483187
TI  - Validation of Eupatorium triplinerve Vahl leaves, a skin care herb from East
      Kalimantan, using a melanin biosynthesis assay.
AB  - In searching for a new material made from natural resources that could be used as
      a whitening agent, we focused on the plants used for skin treatment by the native
      people of East Kalimantan. The methanol extract of the leaves of Eupatorium
      triplinerve Vahl showed antimelanogenesis activity in a melanin biosynthesis
      assay. By activity-guided fractionation, 7-methoxycoumarin (1) was isolated as an
      active compound. The IC50 of 1 on mushroom tyrosinase was 2360 MUM (L-tyrosine
      was used as the substrate) and above 2840 MUM (L-DOPA was used as the substrate),
      respectively. Regarding melanin formation inhibition in B16 melanoma cells, the
      IC50 of 1 was 1780 MUM with 83% cell viability at IC50. Based on these results,
      we validated that the leaf extract is in line with the traditional use of the
      Dayak tribe in East Kalimantan.

PMID- 22483188
TI  - An experimental investigation on thermal exposure during bone drilling.
AB  - This study presents an experimental investigation of the effects of spindle
      speed, feed rate, and depth of drilling on the temperature distribution during
      drilling of the cortical section of the bovine femur. In an effort to reduce
      measurement uncertainties, a new approach for temperature measurements during
      bone drilling is presented in this study. The new approach is based on a setup
      for precise positioning of multiple thermocouples, automated data logging system,
      and a computer numerically controlled (CNC) machining system. A battery of
      experiments that has been performed to assess the uncertainty and repeatability
      of the new approach displayed adequate results. Subsequently, a parametric study
      was conducted to determine the effects of spindle speed, feed rate, hole depth,
      and thermocouple location on the measured bone temperature. This study suggests
      that the exposure time during bone drilling far exceeds the commonly accepted
      threshold for thermal injury, which may prevail at significant distances from the
      drilled hole. Results of this study suggest that the correlation of the thermal
      exposure threshold for bone injury and viability should be further explored.

PMID- 22483189
TI  - How far is real life from COPD therapy guidelines? An Italian observational
      study.
AB  - BACKGROUND: According to the GOLD international guidelines, the treatment of
      chronic obstructive pulmonary disease (COPD) should be proportional to the
      severity of airflow obstruction graded according to FEV(1)% predicted. Regular
      treatment with long-acting bronchodilators should be prescribed for symptomatic
      patients with FEV(1) < 80%. Inhaled corticosteroids should be added in patients
      with FEV(1) < 50% predicted and frequent exacerbations. AIM: To investigate
      whether pulmonologists follow the GOLD guidelines when prescribing treatment for
      COPD. METHODS: A multicenter, cross-sectional, observational study was carried
      out in 49 Pulmonary Units evenly distributed throughout the country. For each
      patient the demographic, clinical data and the current therapies were registered
      in an electronic database. RESULTS: 4094 patients (mean age: 70.9 +/- 9.4; males
      72.4%, female 27.6%) were enrolled. Disease severity was classified as: mild
      (745), moderate (1722), severe (923), very severe (704). Irrespective of disease
      severity, inhaled corticosteroids alone or in combination with long-acting
      bronchodilators were used in 15.2% and 66.8% of patients, respectively. The
      appropriateness of the pharmacological treatment of the COPD patients was defined
      in accordance with the GOLD recommendations. The treatment was appropriate in
      37.9% of patients and inappropriate in 62.1%, p < 0.0001. The inappropriateness
      was due to under-prescription in 7.2% and to over-prescription in 54.9% of
      patients. The presence and the number of exacerbations represented an important
      trigger for over-prescription at stages I and II. CONCLUSIONS: This study shows
      that there is a poor relationship between the recommendations of the GOLD
      international guidelines and current clinical practice, and that exacerbations
      may play a role in over-prescription.

PMID- 22483190
TI  - Clinical significance of Candida colonization of intravascular catheters in the
      absence of documented candidemia.
AB  - In order to assess the significance of Candida colonization of intravascular
      catheters (IVC) in patients without documented candidemia, we retrospectively
      reviewed all Candida-positive IVC tip cultures over a 4-year period. Cases were
      defined as those with a culture yielding >=15 colony-forming units of Candida
      spp. that either did not have blood cultures (BC) taken or had concomitant BC
      negative for Candida. Patients were followed up until death or 8 months after
      discharge. Risk factors for poor outcome following IVC removal (death,
      candidemia, or Candida-related complication) were analyzed. We analyzed a total
      of 40 patients. Overall mortality was 40.0%, with no death directly attributed to
      Candida infection. Twenty-two patients received antifungal therapy at the time of
      IVC removal. Only 1 patient developed a metastatic complication (chorioretinitis)
      attributable to transient candidemia (2.5% of the global cohort and 3.7% among
      those with concomitant BC). There were no cases of subsequent candidemia. In the
      multivariate analysis, the use of antifungal therapy did not show any impact on
      the risk of poor outcome. The risk of invasive disease in patients with isolated
      IVC colonization by Candida seems to be low. Nevertheless, the initiation of
      systemic antifungal therapy should be carefully considered in such context.

PMID- 22483191
TI  - Direct testing of bronchoalveolar lavages from ventilator-associated pneumonia
      patients.
AB  - In line with a rapid de-escalation of empirical antimicrobial therapy, this study
      assessed the validity of an E-test-based direct specimen testing method on
      bronchoalveolar lavage (BAL) samples from ventilator-associated pneumonia (VAP)
      patients. E-test strips were directly applied onto Mueller-Hinton agar plates
      seeded with BAL samples and read after 24 h of incubation. In parallel, the BAL
      samples were analyzed by the routine diagnostic laboratory. The microbroth
      dilution approach was used as a control method. In a cohort of 20 patients, 135
      microorganism-antibiotic combinations were studied. Total agreement between the 2
      methods was achieved for 88.9% combinations, with 1.5% very major errors
      (isolates susceptible by E-test and reported resistant by the diagnostic
      laboratory) and 9.6% major errors (isolates resistant by E-test and reported
      susceptible by the diagnostic laboratory). These results indicate that applying E
      test directly on BAL samples is a promising method for obtaining susceptibility
      data after 24 h in critical patients with VAP.

PMID- 22483193
TI  - Probiotics in necrotizing enterocolitis: more questions than answers?

PMID- 22483194
TI  - Analysis of polarized secretion of fucosylated alpha-fetoprotein in HepG2 cells.
AB  - Fucosylated alpha-fetoprotein (AFP) is a more specific biomarker for
      hepatocellular carcinoma (HCC) than AFP. However, the mechanisms underlying the
      increase in fucosylated AFP in sera of HCC patients remain largely unknown.
      Recently, we reported that fucosylation is a possible signal for the secretion of
      hepatic glycoproteins into bile and that the fucosylation-based sorting machinery
      might be disrupted in the liver bearing HCC. In this study, we investigated the
      selective secretion of fucosylated AFP into bile canaliculus (BC) structures of
      the human hepatoma cell line HepG2. The proportion of fucosylated AFP in BC
      structures was higher than that in the medium, as judged by lectin affinity
      electrophoresis. Suppression of fucosylation by the double knock-down of GDP
      mannose-4,6-dehydratase and the human homologue of GDP-4-keto-6-deoxymannose-3,5
      epimerase-4-reductase, which contribute to the synthesis of GDP-fucose, a donor
      substrate for fucosyltransferases, did not decrease the proportion of fucosylated
      AFP in BC structures but decreased this proportion in conditioned medium.
      Furthermore, increased AFP fucosylation was observed in medium, but not in BC
      structures, upon adding free fucose. These results suggest that saturation of
      fucosylated AFP in BC structures is accompanied by its increase in conditioned
      medium, probably leading to increased fucosylated AFP in sera of HCC patients.

PMID- 22483195
TI  - Late onset (22 years) of simultaneous tonsillar and cervical lymph node
      metastases from breast ductal carcinoma.
AB  - Breast cancer is the leading cause of cancer-related mortality in women
      worldwide; the most common metastatic sites are lymph nodes, lung, liver, and
      brain. Tonsil metastases from breast cancer are extremely rare. Herein, we report
      a case of a 74-year-old woman with simultaneous occurrence of tonsillar and
      cervical lymph nodes metastases after a disease-free interval of 22 years.

PMID- 22483196
TI  - Beneficial effects of reading aloud and solving simple arithmetic calculations
      (learning therapy) on a wide range of cognitive functions in the healthy elderly:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Almost all cognitive functions decline with age. Results of previous
      studies have shown that cognitive training related to everyday life (reading
      aloud and solving simple arithmetic calculations), namely learning therapy, can
      improve two cognitive function (executive functions and processing speed) in
      elderly people. However, it remains unclear whether learning therapy engenders
      improvement of various cognitive functions or not. We investigate the impact of
      learning therapy on various cognitive functions (executive functions, episodic
      memory, short-term memory, working memory, attention, reading ability, and
      processing speed) in healthy older adults. METHODS: We use a single-blinded
      intervention with two parallel groups (a learning therapy group and a waiting
      list control group). Testers are blind to the study hypothesis and the group
      membership of participants. Through an advertisement in local newspaper, 64
      healthy older adults are recruited. They will be assigned randomly to a learning
      therapy group or a waiting list control group. In the learning therapy group,
      participants are required to perform two cognitive tasks for 6 months: reading
      Japanese aloud and solving simple calculations. The waiting list group does not
      participate in the intervention. The primary outcome measure is the Stroop test
      score: a measure of executive function. Secondary outcome measures are
      assessments including the following: verbal fluency task, logical memory, first
      and second names, digit span forward, digit span backward, Japanese reading test,
      digit cancellation task, digit symbol coding, and symbol search. We assess these
      outcome measures before and after the intervention. DISCUSSION: This report is
      the first study which investigates the beneficial effects of learning therapy on
      a wide range of cognitive functions of elderly people. Our study provides
      sufficient evidence of learning therapy effectiveness. Most cognitive functions,
      which are correlated strongly with daily life activities, decrease with age.
      These study results can elucidate effects of cognitive training on elderly
      people. TRIAL REGISTRATION: This trial was registered in The University Hospital
      Medical Information Network Clinical Trials Registry (No. UMIN000006998).

PMID- 22483197
TI  - Baroreflex function in females: changes with the reproductive cycle and
      pregnancy.
AB  - This review briefly describes the changes in baroreflex function that occur
      during female reproductive life, specifically during the reproductive cycle and
      pregnancy. The sensitivity or gain of baroreflex control of heart rate and
      sympathetic activity fluctuates during the reproductive cycle, reaching a peak
      when gonadal hormone levels increase, during the follicular phase in women and
      proestrus in rats. The increase in baroreflex sensitivity (BRS) is likely
      mediated by estrogen because ovariectomy in rats eliminates the BRS increase, the
      cyclic profile of changes in BRS mirror the changes in estrogen, and estrogen
      acts in the brainstem to increase BRS. In contrast, pregnancy depresses both BRS
      and the maximal level of sympathetic activity and heart rate evoked by severe
      hypotension. The decrease in BRS may be mediated by a reduction in the actions of
      insulin in the arcuate nucleus to support the baroreflex. In addition, increased
      levels of the neurosteroid progesterone metabolite 3alpha-OH-DHP act downstream
      in the rostral ventrolateral medulla to suppress maximal baroreflex increases in
      sympathetic activity. Consequently, these changes in baroreflex function impair
      blood pressure regulation in the presence of hypotensive challenges such as
      orthostasis and hemorrhage, a common event during delivery. As a result,
      peripartum hemorrhage is a major cause of human maternal death.

PMID- 22483198
TI  - Third nerve palsy induced by a ruptured anterior communicating artery aneurysm.
AB  - Ruptured anterior communicating artery aneurysm presenting with complete third
      nerve palsy is genuinely rare. We herein report one such case resulting from an
      interpeduncular haematoma. Three months after the coiling, the patient had fully
      recovered. This case adds a new branch to the aetiology-to-prognostic decision
      making tree of third nerve palsies.

PMID- 22483199
TI  - Radiofrequency thermocoagulation for trigeminal neuralgia without intra-operative
      patient waking.
AB  - OBJECTIVE: It is proposed that radiofrequency thermocoagulation (RFT) under
      general anaesthesia without waking the patient intra-operatively, which is
      usually performed to confirm lesion location, will reduce the peri-operative
      discomfort and anxiety suffered by patients. METHODS: A retrospective review of
      all procedures, identified through standard hospital audit codes and performed by
      a single surgeon from 2000 to 2007. Postal questionnaires were sent to all
      eligible patients. Outcome criteria included pain relief, adverse events and
      patients' views on satisfaction, timing and outcomes. A Kaplan-Meier plot was
      used to determine actuarial rates of pain relief. RESULTS: Follow-up was
      available for 84% (37/44) of patients. Complete post-operative pain relief was
      96% (42/44). The actuarial rates of complete pain relief at 6, 12, 24 and 36
      months were 89%, 79%, 66% and 43%. No patients reported an outcome that did not
      meet their expectations while 71% (20/28) had an outcome that was better than
      their expectation. Serious complications included corneal numbness affecting 12%
      (5/41), but no cases of keratitis and a single case of anaesthesia dolorosa.
      CONCLUSIONS: Not waking a patient intra-operatively when performing a RFT is a
      viable treatment option that results in excellent early pain relief, comparable
      to results in the literature and without an increase in complications. Patient
      reported outcomes indicate a high rate of satisfaction and are a novel addition
      to our understanding of the procedure; there is no comparable data in the
      literature documenting patient satisfaction outcomes when the procedure is
      performed with patient waking.

PMID- 22483200
TI  - Non-pharmacological prevention of major depression among community-dwelling older
      adults: a systematic review of the efficacy of psychotherapy interventions.
AB  - Depression is a major public health burden among the aging population. While
      older adults prefer non-pharmacological treatment, few options for psychotherapy
      are available in primary care settings, which is where older adults tend to
      receive mental health services. Indicated prevention is a cost-effective, public
      health approach to prevent major depressive disorder among people with depressive
      symptoms who do not yet meet standard criteria for major depression. We
      critically reviewed randomized controlled trials (RCTs) that assessed the
      efficacy of psychotherapy among community-dwelling older adults with subthreshold
      depression (depressive symptoms that do not meet standard criteria for major
      depression). We examined the intervention types, results, internal validity, and
      external validity of five studies. We used the United States Preventive Services
      Task Force (USPSTF) guidelines to rate the quality of the studies and to provide
      recommendations. Results suggest that psychotherapy is a safe and cost-effective
      method to reduce the public health burden of depression among older adults with
      subthreshold depression.

PMID- 22483201
TI  - Recombinant live vaccine candidates against tuberculosis.
AB  - Tuberculosis (TB) remains among the most deadly health threats to humankind
      despite availability of several potent antibiotics and a vaccine, bacille
      Calmette-Guerin (BCG). BCG partially protects children but not adults from the
      disease. Growing knowledge of the molecular basis of infection, immunity, and
      pathology in TB has driven various approaches, which strive to complement or
      replace BCG with more effective vaccines. Three recombinant live TB vaccine
      candidates have entered clinical trials. These candidates have been genetically
      engineered to be attenuated, to overexpress TB antigens and/or to secrete
      bacterial perforins, ultimately seeking to trigger a robust immune response
      thereby providing long-lasting protection against TB.

PMID- 22483202
TI  - Cell-free biology: exploiting the interface between synthetic biology and
      synthetic chemistry.
AB  - Just as synthetic organic chemistry once revolutionized the ability of chemists
      to build molecules (including those that did not exist in nature) following a
      basic set of design rules, cell-free synthetic biology is beginning to provide an
      improved toolbox and faster process for not only harnessing but also expanding
      the chemistry of life. At the interface between chemistry and biology, research
      in cell-free synthetic systems is proceeding in two different directions: using
      synthetic biology for synthetic chemistry and using synthetic chemistry to
      reprogram or mimic biology. In the coming years, the impact of advances inspired
      by these approaches will make possible the synthesis of nonbiological polymers
      having new backbone compositions, new chemical properties, new structures, and
      new functions.

PMID- 22483203
TI  - Combining chromatography and chemometrics for the characterization and
      authentication of fats and oils from triacylglycerol compositional data--a
      review.
AB  - The characterization and authentication of fats and oils is a subject of great
      importance for market and health aspects. Identification and quantification of
      triacylglycerols in fats and oils can be excellent tools for detecting changes in
      their composition due to the mixtures of these products. Most of the
      triacylglycerol species present in either fats or oils could be analyzed and
      identified by chromatographic methods. However, the natural variability of these
      samples and the possible presence of adulterants require the application of
      chemometric pattern recognition methods to facilitate the interpretation of the
      obtained data. In view of the growing interest in this topic, this paper reviews
      the literature of the application of exploratory and unsupervised/supervised
      chemometric methods on chromatographic data, using triacylglycerol composition
      for the characterization and authentication of several foodstuffs such as olive
      oil, vegetable oils, animal fats, fish oils, milk and dairy products, cocoa and
      coffee.

PMID- 22483204
TI  - Locally linear embedding method for dimensionality reduction of tissue sections
      of endometrial carcinoma by near infrared spectroscopy.
AB  - Locally linear embedding (LLE) is introduced here as a nonlinear compression
      method for near infrared reflectance spectra of endometrial tissue sections. The
      LLE has been evaluated by using support vector machine (SVM) classifiers and the
      projected difference resolution (PDR) method. Synthetic data sets devised to
      resemble near-infrared spectra of tissue samples were used to characterize the
      performance of the LLE. The LLE was compared using principal component
      compression (PCC) method to evaluate nonlinear and linear compression. For a set
      of real tissue samples, if the compressed data were not range-scaled prior to SVM
      classification, the principal component compressed data gave an average
      prediction rate of 39+/-2% while the LLE 94+/-2%; if range-scaled after
      compression, the LLE and PCC performed evenly, with maximum average prediction
      values of 94+/-2% and 93+/-2%, respectively. The SVM without compression yielded
      a classification rate of 92+/-2%. The prediction accuracy was consistent with PDR
      results. Without the second derivative preprocessing, the classification rates
      were 90+/-3%, 89+/-2%, and 78+/-2% for the LLE compressed, the PCC, and no
      compression classifications by the SVM, respectively.

PMID- 22483205
TI  - Estimation of measurement uncertainty of pesticides, polychlorinated biphenyls
      and polyaromatic hydrocarbons in sediments by using gas chromatography-mass
      spectrometry.
AB  - The evaluation of the uncertainty associated to analytical methods is essential
      in order to demonstrate quality of a result. However, there is often lack of
      information about uncertainty of methods to estimate persistent organic
      pollutants concentration in complex matrix. Current work has thoroughly evaluated
      uncertainty associated to quantification of several organochloride pesticides,
      PCBs and PAHs in sediments. A discussion of the main contributions to the overall
      uncertainty is reported, allowing authors to establish the accuracy of results
      and plan future improvements. Combined uncertainties ranged between 5-9%
      (pesticides), 4-7% (PCBs) and 5-10% (PAHs), being uncertainty derived of
      calibration the main contribution. Also, the analytical procedure was validated
      analysing a standard reference material (IAEA-408).

PMID- 22483206
TI  - Recognition of chemical compounds in contaminated water using time-dependent
      multiple dose cellular responses.
AB  - An early determination of toxicant compounds of water contaminations can gain
      critical time to protect citizens' health and save substantial amounts of medical
      costs. To determine toxins in real time, a multi-dose classification algorithm
      using cellular state variable identification (CSVID) is developed in this paper.
      First, the dynamic cytotoxicity response profiles of living cells are measured
      using a real-time cell electronic sensing (RT-CES) system. Changes in cell number
      expressed as cell index (CI) are recorded on-line as time series. Then CSVID,
      which reflects the cell killing, cell lysis and certain cellular pathological
      changes, is extracted from those dynamic cellular responses. Finally, a support
      vector machine (SVM) algorithm based on CSVID is employed to classify chemical
      compounds and determine their analogous cellular response pathway. In order to
      increase the classification accuracy, a majority vote of the class labels is also
      proposed. Several validation studies demonstrate that CSVID-based classification
      algorithm has great potential in distinguishing the cytotoxicity response of the
      cells in the presence of toxins.

PMID- 22483207
TI  - Study on the application of reduced graphene oxide and multiwall carbon nanotubes
      hybrid materials for simultaneous determination of catechol, hydroquinone, p
      cresol and nitrite.
AB  - In this paper, the reduced graphene oxide and multiwall carbon nanotubes hybrid
      materials (RGO-MWNTs) were prepared and a strategy for detecting environmental
      contaminations was proposed on the basis of RGO-MWNTs modified electrode. The
      hybrid materials were characterized by the scanning electron microscopy (SEM),
      atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and N(2)
      sorption-desorption isotherms. Due to the excellent catalytic activity, enhanced
      electrical conductivity and high surface area of the RGO-MWNTs, the simultaneous
      measurement of hydroquinone (HQ), catechol (CC), p-cresol (PC) and nitrite
      (NO(2)(-)) with four well-separate peaks was achieved at the RGO-MWNTs modified
      electrode. The linear response ranges for HQ, CC, PC and NO(2)(-) were 8.0-391.0
      MUM, 5.5-540.0 MUM, 5.0-430.0 MUM and 75.0-6060.0 MUM, correspondingly, and the
      detection limits (S/N=3) were 2.6 MUM, 1.8 MUM, 1.6 MUM and 25.0 MUM,
      respectively. The outstanding film forming ability of RGO-MWNTs hybrid materials
      endowed the modified electrode enhanced stability. Furthermore, the fabricated
      sensor was applied for the simultaneous determination of HQ, CC, PC and NO(2)(-)
      in the river water sample.

PMID- 22483208
TI  - In-syringe demulsified dispersive liquid-liquid microextraction and high
      performance liquid chromatography-mass spectrometry for the determination of
      trace fungicides in environmental water samples.
AB  - An in-syringe demulsified dispersive liquid-liquid microextraction (ISD-DLLME)
      technique was developed using low-density extraction solvents for the highly
      sensitive determination of the three trace fungicides (azoxystrobin,
      diethofencarb and pyrimethanil) in water samples by high performance liquid
      chromatography-mass spectrometry chromatography-diode array detector/electrospray
      ionisation mass spectrometry. In the proposed technique, a 5-mL syringe was used
      as an extraction, separation and preconcentration container. The emulsion was
      obtained after the mixture of toluene (extraction solvent) and methanol
      (dispersive solvent) was injected into the aqueous bulk of the syringe. The
      obtained emulsion cleared into two phases without centrifugation, when an aliquot
      of methanol was introduced as a demulsifier. The separated floating organic
      extraction solvent was impelled and collected into a pipette tip fitted to the
      tip of the syringe. Under the optimal conditions, the enrichment factors for
      azoxystrobin, diethofencarb and pyrimethanil were 239, 200, 195, respectively.
      The limits of detection, calculated as three times the signal-to-noise ratio (SN(
      1)), were 0.026 MUg L(-1) for azoxystrobin, 0.071 MUg L(-1) for diethofencarb and
      0.040 MUg L(-1) for pyrimethanil. The repeatability study was carried out by
      extracting the spiked water samples at concentration levels of 0.02 MUg mL(-1)
      for all the three fungicides. The relative standard deviations varied between 4.9
      and 8.2% (n=5). The recoveries of all the three fungicides from tap, lake and
      rain water samples at spiking levels of 0.2, 1, 5 MUg L(-1) were in the range of
      90.0-105.0%, 86.0-114.0% and 88.6-110.0%, respectively. The proposed ISD-DLLME
      technique was demonstrated to be simple, practical and efficient for the
      determination of different kinds of fungicide residues in real water samples.

PMID- 22483209
TI  - Preparation of Fe3O4 nanoparticle enclosure hydroxylated multi-walled carbon
      nanotubes for the determination of aconitines in human serum samples.
AB  - A magnetic carbon nanomaterial for Fe(3)O(4) enclosure hydroxylated multi-walled
      carbon nanotubes (Fe(3)O(4)-EC-MWCNTs-OH) was prepared by the aggregating effect
      of Fe(3)O(4) nanoparticle on MWCNTs-OH, and combined with high-performance liquid
      chromatography (HPLC)/diode array detection (DAD) to determine the aconitines
      (aconitine, hypaconitine and mesaconitine) in human serum samples. Compared with
      other extraction modes investigated in experiment, Fe(3)O(4)-EC-MWCNTs-OH
      sorbents showed a good affinity to target analytes. Some important parameters
      that could influence extraction efficiency of aconitines, including the
      extraction mode, amounts of Fe(3)O(4)-EC-MWCNTs-OH, pH of sample solution,
      extraction time, desorption solvent and desorption time, were optimized. Under
      optimal conditions, the recoveries of spiked serum samples were between 98.0% and
      103.0%; relative standard deviations (RSDs) ranged from 0.9% to 6.2%. The
      correlation coefficients varied from 0.9996 to 0.9998. The limits of detection
      ranged from 3.1 ng mL(-1) to 4.1 ng mL(-1) at a signal-to-noise ratio of 3. The
      experimental results showed that the proposed method was feasible for the
      analysis of aconitines in serum samples.

PMID- 22483210
TI  - A novel sorptive extraction method based on polydimethylsiloxane frit for
      determination of lung cancer biomarkers in human serum.
AB  - In this study, a porous polypropylene frit was coated with polydimethylsiloxane
      (PDMS) as extraction medium, based on the home-made PDMS-frit, a rapid, simple
      and sensitive sorptive extraction method was established for analysis of
      potential biomarkers of lung cancer (hexanal and heptanal) in human serum
      samples. In the method, derivatization and extraction occurred simultaneously on
      the PDMS-frit, then the loaded frit was ultrasonically desorbed in acetonitrile.
      Polymerization, derivatization-extraction and desorption conditions were
      optimized. Under the optimal conditions, satisfactory results were gained, a wide
      linear application range was obtained in the range of 0.002-5.0 MUmol L(-1)
      (R>0.997) for two aldehydes, the detection limits (SN(-1)=3) were 0.5 nmol L(-1)
      for hexanal and 0.4 nmol L(-1) for heptanal. The relative standard deviations
      (RSDs, n=5) of the method were below 7.9% and the recoveries were above 72.7% for
      the spiked serum. All these results hint that the proposed method is potential
      for disease markers analysis in complex biological samples.

PMID- 22483211
TI  - A simple, reproducible and sensitive spectrophotometric method to estimate
      microalgal lipids.
AB  - Quantification of total lipids is a necessity for any study of lipid production
      by microalgae, especially given the current interest in microalgal carbon capture
      and biofuels. In this study, we employed a simple yet sensitive method to
      indirectly measure the lipids in microalgae by measuring the fatty acids (FA)
      after saponification. The fatty acids were reacted with triethanolamine-copper
      salts (TEA-Cu) and the ternary TEA-Cu-FA complex was detected at 260 nm using a
      UV-visible spectrometer without any colour developer. The results showed that
      this method could be used to analyse low levels of lipids in the range of nano
      moles from as little as 1 mL of microalgal culture. Furthermore, the structure of
      the TEA-Cu-FA complex and related reaction process are proposed to better
      understand this assay. There is no special instrument required and the method is
      very reproducible. To the best of our knowledge, this is the first report of the
      use of UV absorbance of copper salts with FA as a method to estimate lipids in
      algal cultures. It will pave the way for a more convenient assay of lipids in
      microalgae and can readily be expanded for estimating lipids in other biological
      systems.

PMID- 22483212
TI  - Desalting of phosphopeptides by tandem polypyrrole-c18 reverse phase micropipette
      tip (TMTip(PPY-C18)) based on hybrid electrostatic, Pi-Pi stacking and
      hydrophobic interactions for mass spectrometric analysis.
AB  - Desalting and concentration of peptides using reverse phase (RP) C18
      chromatographic material based on hydrophobic interaction is a routine approach
      used in mass spectrometry (MS)-based proteomics. However, MS detection of small
      hydrophilic peptides, in particular, phosphopeptides that bear multiple negative
      charges, is challenging due to the insufficient binding to C18 stationary phase.
      We described here the development of a new desalting method that takes the unique
      properties of polypyrrole (PPY). The presence of positively charged nitrogen
      atoms under acidic conditions and polyunsaturated bonds in polypyrrole provide a
      prospect for enhanced adsorption of phosphopeptides or hydrophilic peptides
      through extra electrostatic and Pi-Pi stacking interactions in addition to
      hydrophobic interactions. In tandem with reversed phase C18 chromatographic
      material, the new type of desalting method termed as TMTip(PPY-C18) can
      significantly improve the MS detection of phosphopeptides with multiple phosphate
      groups and other small hydrophilic peptides. It has been applied to not only
      tryptic digest of model proteins but also the analysis of complex lysates of
      zebrafish eggs. The number of detected phosphate groups on a peptide ranged from
      1 to 6. Particularly, polypyrrole based method can also be used in basic
      condition. Thus it provides a useful means to handle peptides that may not be
      detectable in acidic condition. It can be envisioned that the TMTip(PPY-C18)
      should be able to facilitate the exploration of large scale phosphoproteome.

PMID- 22483213
TI  - Colorimetric detection of cholesterol with G-quadruplex-based DNAzymes and ABTS2
      .
AB  - A novel colorimetric method for detection of cholesterol was developed with hemin
      G-quadruplex DNAzyme by transducing oxidation of cholesterol into the color
      change of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt
      (ABTS(2-)). Oligonucleotide 5'-GTGGGTAGGGCGGGTTGG-3' (Oligo-1) formed G
      quadruplex structure in the presence of K(+), it acted as a horseradish
      peroxidase (HRP) mimicking DNAzyme when binding hemin and catalyzed the oxidation
      of colorless ABTS(2-) to green ABTS(.-) by H(2)O(2), which was produced by the
      reaction of cholesterol and oxygen that catalyzed by cholesterol oxidase.
      Therefore, the oxidation of cholesterol could be transduced into the color change
      of ABTS(2-) by combining these two reactions. Under the optimum conditions, the
      absorbance was proportional to the concentration of cholesterol over the range of
      1.0-30 MUM, with a linear regression equation of A=0.362+0.0256C (C: MUM,
      R=0.998) and a detection limit of 0.10 MUM (3sigma/slope). Moreover, the
      practicability of the assay in the detection of cholesterol in human serum was
      studied as well.

PMID- 22483214
TI  - Gap site-specific rapid formation of fluorescent silver nanoclusters for label
      free DNA nucleobase recognition.
AB  - Silver nanoclusters (Ag NCs) templated with DNAs have attracted much attention as
      novel fluorophores because of their convenient emission tunability by the
      sequence and length of the template DNAs. However, the precise production of Ag
      NCs in a site-specific manner still remains a challenge to attain highly
      selective and label-free DNA recognition. Here we exploited the availability of a
      gap site in DNA duplexes as a new scaffold for the synthesis of Ag NCs. Compared
      to the commonly used DNA templates for the creation of Ag NCs, the gap site in
      DNA duplexes was found to facilitate the rapid formation of the fluorescent Ag
      NCs without sacrifice of their bright emission and excellent stability. We found
      that fluorescent Ag NCs were highly selectively formed when cytosine faced toward
      the gap site in DNA duplexes, and they were in situ utilized as readout by signal
      on manner for the DNA mutation assays. This base-selective growth of the
      fluorescent Ag NCs at the gap site would find promising applications in practical
      detection of single nucleotide polymorphism (SNP) and construction of DNA-based
      functional sensors with label-free and cost-effective merits.

PMID- 22483215
TI  - Development of a novel label-free amperometric immunosensor for the detection of
      okadaic acid.
AB  - Okadaic acid (OA), a lipophilic phycotoxin is mainly produced by toxigenic
      dinoflagellates. The need to develop high performing methods for OA analysis able
      to improve the traditional ones is evident. In this work, a novel experimental
      methodology for label-free detection of OA was developed. Protein G magnetic
      beads (protein-G-MBs) modified gold electrode was used to immobilize anti-OA
      monoclonal antibody (anti-OA-MAb). Preliminary, colorimetric tests were performed
      in order to validate protein-G-MBs and anti-OA-MAb reaction. Electrochemical
      detection was carried out by differential pulse voltammetry in ferri/ferrocyanide
      solution. The limit of detection value obtained (0.5 MUg L(-1)) validated the
      developed electrochemical immunosensor as a promising tool for routine use. The
      matrix effect and the recovery rate were also assessed with real samples, showing
      a good percentage of recovery.

PMID- 22483216
TI  - Development of a multi-component chemically reactive detection conjugate for the
      determination of Hg(II) in water samples.
AB  - Mercury ions (Hg(II)) are considered highly toxic and hazardous element even at
      low levels. The contamination of Hg(II) is a global problem. To develop selective
      and sensitive technique for the detection of Hg(II) has attracted considerable
      attention. In this study, a multi-component chemically reactive detection
      conjugate for determination of Hg(II) has been synthesized and a competitive
      format assay was proposed. In the technique, the chemically reactive capture
      conjugate was coated on the plate. The reactive detection conjugate was then
      captured by the capture conjugate. TMB solution was added and catalyzed by HRP
      molecules immobilized on AuNPs. Finally, the developed enzymatic signal was
      measured at 450 nm. The linear range of the assay was 0.35-350 ppb with a
      detection limit of 0.1 ppb. The average recoveries of Hg(II) from mineral water,
      tap water and lake water were 100.03%, 103.13% and 102.03%, respectively. All
      coefficients of variation (CVs) were less than 10%. The results are closely
      correlated with those from inductively coupled plasma mass spectrometry (ICP-MS),
      which indicated that the developed technique is a reliable method for and
      sensitive detection of Hg(II) in water samples.

PMID- 22483217
TI  - Buffer enhanced bioluminescence resonance energy transfer sensor based on Gaussia
      luciferase for in vitro detection of protease.
AB  - Bioluminescence resonance energy transfer (BRET) has gained favors in recent
      years as a detection technology for protease activity due to its extreme
      reliability, high sensitivity and low intrinsic backgrounds. Because of the
      sensitivity of the donors, substrates and the acceptors, it is expected that BRET
      systems are sensitive to buffer environments. However, no systematic study has
      been reported on how buffer components would affect the BRET ratio, and thus
      affect the determination of protease activity based on BRET. We present here that
      several environmental factors, including buffer agents, pH and divalent metal
      ions, influenced BRET ratio significantly, when humanized Gaussia luciferase
      (hGluc) was utilized as the donor and enhanced yellow fluorescence protein (EYFP)
      as the acceptor. Based on these findings, an enhancing solution was optimized to
      improve the performance of the BRET sensor for analysis of enterokinase activity
      in vitro, resulting in 10-fold and 7-fold improvement of the sensitivity and the
      detection limit, respectively. We anticipate the system will be applicable for
      improving performance of other in vitro BRET protease sensors, especially when
      the optimal conditions for protease activity would severely affect the BRET
      signal.

PMID- 22483218
TI  - Sequential-dissociation kinetics of non-covalent complexes of DNA with multiple
      proteins in separation-based approach: general theory and its application.
AB  - Binding of multiple proteins to DNA is crucial in many regulatory cellular
      processes. The kinetics of assembly and disassembly of DNA-multiple protein
      complexes is very difficult to study in detail due to the lack of suitable
      experimental approaches. A separation-based approach has been recently proposed
      to resolve disassembly kinetics of such complexes. While conceptually simple, the
      separation-based approach generates experimental data with very complex patterns.
      The analysis of these patterns is a challenging problem on its own. Here we
      report on a mathematical approach that can extract a solution for the
      experimental data obtained in separation-based analysis of sequential
      dissociation of a DNA complex with multiple proteins. This case describes the
      dissociation of proteins one-by-one from the complex. Generally speaking, a
      mathematical solution of such problems requires calculations of multiple
      integrals. Our approach reduces this procedure to taking double integrals and
      constructing their superposition. We tested this approach with the experimental
      data obtained for three-step sequential dissociation of complexes of DNA with two
      protein copies.

PMID- 22483219
TI  - A selective metabolite array for the detection of phosphometabolites.
AB  - Immobilised metal ion affinity (IMA) has been traditionally used specifically for
      the separation of phosphorylated proteins and nucleic acids, in proteomics and
      genomics, respectively. This report describes the novel application of IMA in
      metabolomics for the development of metabolite arrays to detect
      phosphometabolites using a plasma polymer-modified surface. Immobilisation of
      gallium, zirconium, cobalt, copper, zinc, nickel, iron, and chromium to acrylic
      acid plasma polymer followed by subsequent exposure to metabolites (phospho- and
      non-phosphometabolites) was investigated. Results analysed using ToF-SIMS
      suggests that gallium and zirconium exhibit higher phosphometabolite affinity and
      specificity compared to other metals, and can be used to develop metabolite
      arrays for the detection of phosphometabolites.

PMID- 22483220
TI  - Simultaneous qualitative assessment and quantitative analysis of flavonoids in
      various tissues of lotus (Nelumbo nucifera) using high performance liquid
      chromatography coupled with triple quad mass spectrometry.
AB  - Flavonoid composition and concentration were investigated in 12 different tissues
      of 'Ti-1' lotus (Nelumbo nucifera) by high performance liquid chromatography
      equipped with photodiode array detection tandem electrospray ionization mass
      spectrometry (HPLC-DAD-ESI-MS(n)). A total of 20 flavonoids belonging to six
      groups (myricetin, quercetin, kaempferol, isohamnetin, diosmetin derivatives)
      were separated and identified. Myricetin 3-O-galactoside, myricetin 3-O
      glucuronide, isorhamnetin 3-O-glucuronide and free aglycone diometin (3',5,7
      trihydroxy-4'-methoxyflavone) were first reported in lotus. Flavonoid composition
      varied largely with tissue type, and diverse compounds (5-15) were found in leaf
      and flower stalks, flower pistils, seed coats and embryos. Flower tissues
      including flower petals, stamens, pistils, and, especially, reproductive tissue
      fruit coats had more flavonoid compounds (15-17) than leaves (12), while no
      flavonoids were detectable in seed kernels. The flavonoid content of seed embryos
      was high, 730.95 mg 100g(-1) DW (dry weight). As regards the other tissues,
      mature leaf pulp (771.79 mg 100 g(-1) FW (fresh weight)) and young leaves (650.67
      mg 100 g(-1) FW) had higher total flavonoid amount than flower stamens (359.45 mg
      100 g(-1) FW) and flower petals (342.97 mg 100g(-1) FW), while leaf stalks,
      flower stalks and seed coats had much less total flavonoid (less than 40 mg 100
      g(-1) FW).

PMID- 22483221
TI  - Poly (acrylic acid) microchannel modification for the enhanced resolution of
      catecholamines microchip electrophoresis with electrochemical detection.
AB  - A new modification of glass electrophoresis microchips based on poly (acrylic)
      acid immobilization has been performed. It is based on the reaction of PAA with
      an amine functionalized surface, obtained through the bifunctional reagent 3
      aminopropyl triethoxysilane. Parameters affecting all the three steps involved:
      surface activation, silanization and polymer immobilization were optimized
      employing soda-lime glass plates. Characterization by SEM and XPS was carried
      out. Application of the modified microchips to the separation of a model system:
      dopamine (D), epinephrine (E) and norepinephrine (NE), that on the other hand are
      of high clinical relevance was performed employing amperometric detection.
      Modification is necessary for obtaining partial resolution of all the three
      analytes in a microchip with an effective separation length of 30 mm. Situation
      changes from no resolution (Rs) at all (only one peak was achieved for the
      mixture) to a partial resolution (Rs D-NE and Rs NE-E are 0.25 and 0.24
      respectively). Microchips with 60 mm of separation channel were also modified,
      implying this procedure a resolution enhancement (Rs of 0.49 and 0.28 for D-NE
      and NE-E respectively), even when methanol is employed as organic modifier (Rs
      values of 0.70 (D-NE) and 0.66 (NE-E) for a 3% MeOH).

PMID- 22483222
TI  - Cross-cultural adaptation and measurement properties of the Brief Illness
      Perception Questionnaire-Dutch Language Version.
AB  - OBJECTIVE: Ever since Engel's Biopsychosocial Model (1977) emotions, thoughts,
      beliefs and behaviors are accepted as important factors of health. The Brief
      Illness Perception Questionnaire (Brief IPQ) assesses these beliefs. Aim of this
      study was to cross-culturally adapt the Brief IPQ into the Brief IPQ Dutch
      Language Version (Brief IPQ-DLV), and to assess its face validity, content
      validity, reproducibility, and concurrent validity. METHODS: Beaton's guideline
      was used for cross-culturally adaptation. Face and content validity were assessed
      in 25 patients, 15 physiotherapists and 24 first-grade students. Reproducibility
      was established in 27 individuals with chronic obstructive pulmonary disease
      using Cohen's kappa coefficient (K(w)) and the Smallest Detectable Change (SDC).
      Concurrent validity was assessed in 163 patients visiting 11 different physical
      therapists. RESULTS: The Brief IPQ-DLV is well understood by patients, health
      care professionals and first-grade students. Reliability at 1 week for the
      dimensions Consequences, Concern and Emotional response K(w)>0.70, for the
      dimensions Personal control, Treatment control, Identity, K(w)<0.70. A time
      interval of 3 weeks, reliability coefficients were lower for almost all
      dimensions. SDC was between 2.45 and 3.37 points for individual measurement
      purposes and between 0.47 and 0.57 points for group evaluative measurement
      purposes. Concurrent validity showed significant correlations (P<.05) for four
      out of eight illness perceptions (IPs) dimensions. CONCLUSION: The face and
      content properties were found to be acceptable. The reproducibility and
      concurrent validity needs further investigated.

PMID- 22483223
TI  - Editorial [ Special board members issue (Edior-in-chief: Michelle Prudhomme)].

PMID- 22483224
TI  - Electron mobilities of n-type organic semiconductors from time-dependent
      wavepacket diffusion method: pentacenequinone derivatives.
AB  - The electron mobilities of two n-type pentacenequinone derivative organic
      semiconductors, 5,7,12,14-tetraaza-6,13-pentacenequinone (TAPQ5) and 1,4,8,11
      tetraaza-6,13-pentacenequinone (TAPQ7), are investigated with use of the methods
      of electronic structure and quantum dynamics. The electronic structure
      calculations reveal that the two key parameters for the control of electron
      transfer, reorganization energy and electronic coupling, are similar for these
      two isomerization systems, and the charge carriers essentially display one
      dimensional transport properties. The mobilities are then calculated by using the
      time-dependent wavepacket diffusion approach in which the dynamic fluctuations of
      the electronic couplings are incorporated via their correlation functions
      obtained from molecular dynamics simulations. The predicted mobility of TAPQ7
      crystal is about six times larger than that of TAPQ5 crystal. Most interestingly,
      Fermi's golden rule predicts the mobilities very close to those from the time
      dependent wavepacket diffusion method, even though the electronic couplings are
      explicitly large enough to make the perturbation theory invalid. The possible
      reason is analyzed from the dynamic fluctuations.

PMID- 22483225
TI  - Results and unsolved problems following the amendment to the Italian Law on
      assisted reproduction brought about by the Constitutional Court.
AB  - Since the approval of Law N degrees  40/2004, Italian specialists have been
      applying assisted reproductive techniques in compliance with a number of
      restrictions. Several attempts were made to find a solution to the practical and
      ethical issues brought about by this restrictive legislation. Finally, in May
      2009, the Italian Constitutional Court banned most of the limitations. In the
      last year the authors worked together to study the impact of the Italian
      Constitutional Court modifications on assisted reproduction from both a
      gynecological and medico-legal point of view. Despite the clinically positive
      impact of the ruling, a lot of technical and legal unsolved issues still exist.
      Analyzing these problems, the authors stress the importance of a
      multidisciplinary approach to achieve adequate legislation in order to improve
      patients' outcome and avoid "reproductive migration" from Italy to other European
      Countries. New regulation could also be important for practitioners by keeping
      the risk of legal troubles to the minimum.

PMID- 22483226
TI  - In-vivo transducer to measure dynamic mitral annular forces.
AB  - Limited knowledge exists regarding the forces which act on devices implanted to
      the heart's mitral valve. Developing a transducer to measure the peak force
      magnitudes, time rates of change, and relationship with left ventricular pressure
      will aid in device development. A novel force transducer was developed and
      implanted in the mitral valve annulus of an ovine subject. In the post
      cardioplegic heart, septal-lateral and transverse forces were continuously
      measured for cardiac cycles reaching a peak left ventricular pressure of 90 mmHg.
      Each force was seen to increase from ventricular diastole and found to peak at
      mid-systole. The mean change in septal-lateral and transverse forces throughout
      the cardiac cycle was 4.4+/-0.2 N and 1.9+/-0.1 N respectively. During
      isovolumetric contraction, the septal-lateral and transverse forces were found to
      increase at peak rate of 143+/-8 N/s and 34+/-9 N/s, respectively. Combined, this
      study provides the first quantitative assessment of septal-lateral and transverse
      forces within the contractile mitral annulus. The developed transducer was
      successful in measuring these forces whose methods may be extended to future
      studies. Upon additional investigation, these data may contribute to the safer
      development and evaluation of devices aimed to repair or replace mitral valve
      function.

PMID- 22483227
TI  - Accuracy and precision of hind limb foot contact timings of horses determined
      using a pelvis-mounted inertial measurement unit.
AB  - Gait analysis using small sensor units is becoming increasingly popular in the
      clinical context. In order to segment continuous movement from a defined point of
      the stride cycle, knowledge about footfall timings is essential. We evaluated the
      accuracy and precision of foot contact timings of a defined limb determined using
      an inertial sensor mounted on the pelvis of ten horses during walk and trot at
      different speeds and in different directions. Foot contact was estimated from
      vertical velocity events occurring before maximum sensor roll towards the
      contralateral limb. Foot contact timings matched data from a synchronised hoof
      mounted accelerometer well when velocity minimum was used for walk (mean (SD)
      difference of 15 (18)ms across horses) and velocity zero-crossing for trot (mean
      (SD) difference from -4 (14) to 12 (7)ms depending on the condition). The stride
      segmentation method also remained robust when applied to movement data of hind
      limb lame horses. In future, this method may find application in segmenting
      overground sensor data of various species.

PMID- 22483228
TI  - Our capricious vessels: The influence of stent design and vessel geometry on the
      mechanics of intracranial aneurysm stent deployment.
AB  - There is a growing interest in virtual tools to assist clinicians in evaluating
      different procedures and devices for endovascular treatment. In the present study
      we use finite element analysis to investigate the influence of stent design and
      vessel geometry for stent assisted coiling of intracranial aneurysms. Nine
      virtual stenting procedures were performed: three nitinol stent designs ((i) an
      open cell stent resembling the Neuroform, (ii) a generic stiff and (iii) a more
      flexible closed cell design), were deployed in three patient-specific cerebral
      aneurysmatic vessels. We investigated the percentage of strut area covering the
      aneurysm neck, the straightening induced on the cerebrovasculature by the stent
      placement (quantified by the reduction in tortuosity), and stent apposition to
      the wall (quantified as the percentage of struts within 0.2mm of the vessel). The
      results suggest that the open cell design better covers the aneurysm neck (11.0+/
      1.1%) compared to both the stiff (7.8+/-1.6%) and flexible (8.7+/-1.6%) closed
      cell stents, and induces less straightening of the vessel (-5.1+/-1.6% vs. 
      42.9+/-9.8% and -26.9+/-11.9% ). The open cell design has, however, less struts
      apposing well to the vessel wall (56.0+/-6.4%) compared to the flexible (73.4+/
      4.6%) and stiff (70.4+/-5.1%) closed cell design. With the presented study, we
      hope to contribute to and improve aneurysm treatment, using a novel patient
      specific environment as a possible pre-operative tool to evaluate mechanical
      stent behavior in different vascular geometries.

PMID- 22483229
TI  - Modular and scalable load-wall sled buck for pure-lateral and oblique side impact
      tests.
AB  - A considerable majority of side impact sled tests using different types of human
      surrogates has used a load-wall design not specific to subject anthropometry. The
      use of one load-wall configuration cannot accurately isolate and evaluate
      regional responses for the same load-wall geometry. As the anatomy and
      biomechanical responses of the human torso depends on the region, and
      anthropomorphic test devices continue to advance and accommodate regional
      differences, it is important to obtain specific data from sled tests. To achieve
      this goal, the present study designed a scalable modular load-wall consisting of
      the shoulder, thorax, abdomen, and superior and inferior pelvis, and lower limb
      plates. The first five plates were connected to a vertical fixture and the limb
      plate was connected to another fixture. The width, height, and thickness, and the
      gap between plates were modular. Independent adjustments in the coronal and
      sagittal planes allowed region-specific positioning depending on surrogate
      anthropometry, example pelvis width and seated height. Two tri-axial load cells
      were fixed on the contralateral face of each plate of the load-wall to record
      impact force-time histories. The load-wall and vertical fixture design can be
      used to conduct side impact tests with varying vectors, pure-lateral to anterior
      and posterior oblique, by appropriately orienting the load-wall with respect to
      the surrogate. The feasibility of the design to extract region-specific
      biomechanical data was demonstrated by conducting pure-lateral and anterior
      oblique sled tests using two different surrogates at a velocity of 6.7m/s. Uses
      of this design are discussed for different applications.

PMID- 22483230
TI  - Stance and swing phase detection during level and slope walking in the cat:
      effects of slope, injury, subject and kinematic detection method.
AB  - In quadrupeds, there have been limited comparisons of gait timing events
      detection (e.g., paw contact, PC and paw-off, PO) determined from kinematics and
      forceplates. The goal of this study was to investigate the effect of different
      slopes (0, -27, +27 degrees ), recovery times after ankle extensor nerve injury
      and repair (2, 6, 12 weeks), subjects and detection methods on accuracy of
      kinematically derived PC and PO timings during feline walking. Right hindlimb
      kinematics and ground reaction forces (GRF) of 4 cats walking along a sloped
      walkway with embedded forceplates were recorded. A total of 963 walking cycles
      were analyzed. Gait timings were determined from five kinematic methods based on
      displacements, velocities or accelerations of hindlimb markers. GRF based 'gold
      standard' timings for PC and PO were used to determine the systematic and random
      error of kinematic timing. Systematic errors between the kinematic methods
      differed significantly (p<0.05). Methods based on vertical paw peak acceleration
      and velocity gave the smallest systematic errors for PC and PO, respectively. The
      smallest random errors (standard deviations) for PC and PO were demonstrated by
      method based on paw horizontal displacement relative to greater trochanter:
      13.4ms and 6.6ms, respectively. Effects of slope and subject on systematic errors
      of kinematic methods were significant, whereas effects of recovery time after
      nerve injury were not. It was concluded that timing of gait events can be
      determined consistently using kinematics, although adjustments must be made to
      account for the systematic error which varies according to subject and slope
      condition.

PMID- 22483233
TI  - Anaplastic large T-cell lymphoma of the external ear in childhood.
AB  - Anaplastic large T-cell lymphoma is a very rare disease in childhood. The most
      common locations are lymph nodes and skin, while the external ear location is
      uncommon. We present the case of a 6-year-old child with an earlobe tumour.
      Surgical treatment was performed and the anatomopathological results showed
      anaplastic large cell lymphoma. Radiological tests were negative and there was no
      systemic involvement.

PMID- 22483232
TI  - Gram-negative and Gram-positive bacterial infections give rise to a different
      metabolic response in a mouse model.
AB  - Metabolomics has become an important tool to study host-pathogen interactions and
      to discover potential novel therapeutic targets. In an attempt to develop a
      better understanding of the process of pathogenesis and the associated host
      response we have used a quantitative (1)H NMR approach to study the metabolic
      response to different bacterial infections. Here we describe that metabolic
      changes found in serum of mice that were infected with Staphylococcus aureus,
      Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa can
      distinguish between infections caused by Gram-positive and Gram-negative
      bacterial strains. By combining the results of the mouse study with those of
      bacterial footprinting culture experiments, bacterially secreted metabolites
      could be identified as potential bacterium-specific biomarkers for P. aeruginosa
      infections but not for the other strains. Multivariate statistical analysis
      revealed correlations between metabolic, cytokine and physiological responses. In
      TLR4 and TLR2 knockout mice, host-response pathway correlated metabolites could
      be identified and allowed us for the first time to distinguish between bacterial-
      and host-induced metabolic changes. Since Gram-positive and Gram-negative
      bacteria activate different receptor pathways in the host, our results suggest
      that it may become possible in the future to use a metabolomics approach to
      improve on current clinical microbiology diagnostic methods. 

PMID- 22483234
TI  - Immunohistochemical expression of GLUT1 and its correlation with unfavorable
      histology and TP53 codon 72 polymorphism in Wilms tumors.
AB  - Reprogramming of energy metabolism, such as increased glycolysis, is a hallmark
      of cancer cells. One mechanism by which cancer cells fuel glycolysis is through
      increased uptake of glucose across cell membranes via the glucose transporter
      GLUT1. One of the transcriptional repressors of GLUT1 is wild-type TP53, and
      cancer-associated loss of function mutations within the DNA-binding domain of
      TP53 impairs the repressive effect of TP53 on transcriptional activity of the
      GLUT1 gene promoter. Because TP53 mutations are associated with unfavorable
      histology (diffuse anaplasia) in Wilms tumors, we hypothesized increased
      expression of GLUT1 in these tumors. To evaluate this hypothesis, we performed
      tissue microarray-based immunohistochemistry for GLUT1 in a set of 50 Wilms
      tumors, including 5 with unfavorable histology. In a subset of 16 favorable
      histology Wilms tumors, we compared the GLUT1 immunoexpression with TP53 codon 72
      polymorphism status. We found consistently stronger immunoexpression of GLUT1 in
      unfavorable histology Wilms tumors compared to favorable histology Wilms tumors
      (P  =  0.04). We noted that the favorable histology Wilms tumors with a proline
      residue at position 72 of TP53 tended to have higher immunoexpression of GLUT1,
      although this immunoexpression did not reach statistical significance in this
      small set of cases. In summary, our finding of strong GLUT1 immunoexpression in
      unfavorable histology Wilms tumors indicates that these tumors are likely to be 2
      deoxy-2-((18)F)fluoro-d-glucose avid and that GLUT1 should be evaluated as a
      therapeutic target for these tumors that otherwise show resistance to
      conventional therapy.

PMID- 22483235
TI  - Component analysis of propolis collected on Jeju Island, Korea.
AB  - A study of propolis from Jeju Island, located off the southern tip of Korea, led
      to the isolation and identification of eight chalcones: (+/-)-(E)-4'-methoxy-4,2'
      dihydroxy-3'-(2",3"-dihydroxy-3"-methylbutyl)-chalcone, (E,E,E)-4,2',4'
      trihydroxy-3'-(7"-hydroxy-3",7"-dimethyloct-2",5"-dienyl)-chalcone, (+/-)-(E,E)
      4,2',4'-trihydroxy-3'-(5"-hydroxy-3",7"-dimethyloct-2",6"-dienyl)-chalcone, (+/-)
      (E)-4'-methoxy-4,3",4"-trihydroxy-2",2"-dimethyldihydropyrano-(2',3')-chalcone,
      (+/-)-(E)-4'-methoxy-4,3"-dihydroxy-2"-(1"'-hydroxyisopropyl)-dihydrofurano
      (2',3')-chalcone, (-)-(E)-4,4'-dihydroxy-2"-(1"'-hydroxy-1"',5"'-dimethylhex-4"'
      enyl)-dihydrofurano-(2',3')-chalcone, (+)-(E)-4,2'-dihydroxy-2"-methyl-2"
      (3"',4"'-dihydroxy-4"'-methylpentanyl)-2H-pyrano-(3',4')-chalcone and (-)-(E)
      4,2'-dihydroxy-2"-methyl-2"-(3"',4"'-dihydroxy-4"'-methylpentanyl)-2H-pyrano
      (3',4')-chalcone. Nineteen other known compounds were also isolated. Their
      structures were determined by spectroscopic analyses and comparison with
      literature data. The propolis from Jeju Island contained compounds not present in
      propolis from other regions.

PMID- 22483236
TI  - Risk factors for vancomycin-resistant enterococci infection and mortality in
      colonized patients on intensive care unit admission.
AB  - This study examined the incidence of and risk factors for development of
      vancomycin-resistant enterococci (VRE) infection and death in VRE-colonized
      patients in a medical intensive care unit. VRE colonization was identified in 184
      patients (17.6%) in whom VRE perianal swab cultures were obtained. Of these, 28
      (11.9%) developed VRE infection. Control of infectious sources is crucial to
      decrease development of VRE infections and optimize the survival of VRE-colonized
      patients.

PMID- 22483237
TI  - Performance evaluation of filtering facepiece respirators using virus aerosols.
AB  - Physical penetration and infectivity penetration of adenovirus and influenza
      virus aerosols through respirators were measured to better characterize the
      effectiveness of filtering facepiece respirators against airborne virus. A
      physical penetration of 2%-5% was found. However, large sample-to-sample
      variation made it difficult to quantify the difference in physical penetration
      caused by the different virus aerosols. Infectivity penetration of adenovirus was
      much lower than physical penetration, indicating that the latter provides a
      conservative estimate for respirator performance.

PMID- 22483238
TI  - A pilot study to evaluate the effect of Taeumjowi-tang on obesity in Korean
      adults: study protocol for a randomised, double-blind, placebo-controlled,
      multicentre trial.
AB  - BACKGROUND: Obesity, which is described as excessive or abnormal body fat,
      increases the risk of diet-related diseases. In Korea and around the world, the
      prevalence of obesity has grown annually from 1998 to 2008. This growth has
      continued despite various therapeutic efforts. The discovery of new and
      alternative treatments for obesity should be considered an important priority.
      Taeumjowi-tang (TJ001), a traditional Korean medicinal extract consisting of
      eight herbs, is a widely used herbal remedy for obesity in Korea. However, the
      efficacy and safety of TJ001 have not been fully investigated in a clinical
      trial. The purpose of this pilot study is to estimate obesity-related parameters
      and to assess the efficacy and safety of TJ001. METHODS: Our study is a
      randomised, double-blind, placebo-controlled, multicentre clinical trial of
      Taeumjowi-tang (TJ001). For this study, we will recruit obese Korean patients of
      both sexes, ages 18 to 65 years, from four university hospitals. A total of 104
      subjects will be recruited. The participants will receive either 7 g of TJ001 or
      a placebo three times daily for 12 weeks. The primary end point will be the rate
      of subjects who lose at least 5% of their baseline body weight. The secondary end
      points will be changes in body weight, body mass index, waist circumference, hip
      circumference, waist/hip circumference ratio, lipid profiles, body fat
      composition, blood pressure, fasting glucose concentration, C-reactive protein
      and questionnaires related to the quality of life. The outcomes will be measured
      every 4 weeks. The study period will be 12 weeks and will include a total of five
      visits with each subject (at screening and at 0, 4, 8 and 12 weeks). CONCLUSIONS:
      The results of our study will inform various estimates of TJ001 and will serve as
      the basis for a larger-scale trial. This study will assess the efficacy and
      safety of TJ001 as an alternative herbal remedy for obesity. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN87153759.

PMID- 22483239
TI  - Impact of a mutator phenotype on motility and cell adherence in Salmonella
      Heidelberg.
AB  - In this study, we investigated adherence and motility of the hypermutator
      Salmonella enterica Heidelberg B182 bovine strain related to a 12bp deletion in
      mutS. This mutator phenotype was associated with increased adherence to
      epithelial cells and with high expression of fimA as shown by real-time RT-PCR.
      Motility studies showed that fliC were up-regulated in the B182 strain, while
      fljA and fljB were down-regulated. In order to determine if mutated mutS is
      implicated in this genes expression, isogenic strains, derived from a WT strain,
      containing the 12bp deletion in mutS (Delta12bpmutS) or an inactivated mutS
      (DeltamutS) were generated. Delta12bpmutS and DeltamutS strains showed a
      spontaneous mutation rate similar to the environmental strain B182, but exhibited
      lower adherence capacity and fimA expression. In contrast to the fimbriae genes,
      in Delta12bpmutS, fliC expression was up-regulated, but fljA and fljB expression
      were decreased, as in the B182 strain. Only fljB expression was increased in
      DeltamutS mutants. Taken together, our data suggest that mutS alteration does not
      influence fimbriae expression but can impact flagella genes.

PMID- 22483240
TI  - Phylogenetic relationships of Brazilian isolates of Pythium insidiosum based on
      ITS rDNA and cytochrome oxidase II gene sequences.
AB  - Pythium insidiosum is an aquatic oomycete that is the causative agent of
      pythiosis. Advances in molecular methods have enabled increased accuracy in the
      diagnosis of pythiosis, and in studies of the phylogenetic relationships of this
      oomycete. To evaluate the phylogenetic relationships among isolates of P.
      insidiosum from different regions of Brazil, and also regarding to other American
      and Thai isolates, in this study a total of thirty isolates of P. insidiosum from
      different regions of Brazil was used and had their ITS1, 5.8S rRNA and ITS2 rDNA
      (ITS) region and the partial sequence of cytochrome oxidase II (COX II) gene
      sequenced and analyzed. The outgroup consisted of six isolates of other Pythium
      species and one of Lagenidium giganteum. Phylogenetic analyses of ITS and COX II
      genes were conducted, both individually and in combination, using four different
      methods: Maximum parsimony (MP); Neighbor-joining (NJ); Maximum likelihood (ML);
      and Bayesian analysis (BA). Our data supported P. insidiosum as monophyletic in
      relation to the other Pythium species, and COX II showed that P. insidiosum
      appears to be subdivided into three major polytomous groups, whose arrangement
      provides the Thai isolates as paraphyletic in relation to the Brazilian ones. The
      molecular analyses performed in this study suggest an evolutionary proximity
      among all American isolates, including the Brazilian and the Central and North
      America isolates, which were grouped together in a single entirely polytomous
      clade. The COX II network results presented signals of a recent expansion for the
      American isolates, probably originated from an Asian invasion source. Here, COX
      II showed higher levels bias, although it was the source of higher levels of
      phylogenetic information when compared to ITS. Nevertheless, the two markers
      chosen for this study proved to be entirely congruent, at least with respect to
      phylogenetic relationships between different isolates of P. insidiosum.

PMID- 22483241
TI  - Common features of optimal collagen scaffolds that disrupt wound contraction and
      enhance regeneration both in peripheral nerves and in skin.
AB  - The adult mammal responds to severe injury of most organs spontaneously by wound
      contraction and scar formation, rather than by regeneration. In severe skin
      wounds, the ability of porous collagen scaffolds to induce regeneration was found
      to correlate strongly with a reduction in wound contraction rate. Here, we
      present quantitative evidence of a similar positive relationship between the
      extent of disruption of tissue contraction and quality of peripheral nerve
      regeneration in transected rat peripheral nerves. Our observations suggest that
      porous collagen scaffolds enhance regeneration both in injured adult skin and
      peripheral nerves by disrupting the formation of a contractile cell capsule at
      the edges of the wound. Preliminary observations made with other injured organs
      support the hypothesis that capsules or clusters of contractile cells impose a
      universal mechanical barrier during wound healing which, if disrupted
      appropriately, enhances the quality of induced regeneration in a wider range of
      organs.

PMID- 22483242
TI  - The use of carbon nanotubes to induce osteogenic differentiation of human adipose
      derived MSCs in vitro and ectopic bone formation in vivo.
AB  - Carbon nanotubes (CNTs), one of the most concerned nanomaterials, with unique
      electrical, mechanical and surface properties, have been shown suitable for
      biomedical application. In this study, we evaluated attachment, proliferation,
      osteogenic gene expression, ALP/DNA, protein/DNA and mineralization of human
      adipose-derived stem cells cultured in vitro on multi-walled carbon nanotubes
      (MWNTs) and graphite (GP) compacts with the same dimension. Moreover, we assessed
      the effect of these two kinds of compacts on ectopic bone formation in vivo.
      First of all, higher ability of the MWNTs compacts to adsorb proteins, comparing
      with the GP compacts, was shown. During the conventional culture, it was shown
      that MWNTs could induce the expression of ALP, cbfa1 and COLIA1 genes while GP
      could not. Furthermore, alkaline phosphatase (ALP)/DNA and protein/DNA of the
      cell on the MWNTs compacts, was significantly higher than those of the cells on
      the GP compacts. With the adsorption of the proteins in culture medium with 50%
      fetal bovine serum (FBS) in advance, the increments of the ALP/DNA and
      protein/DNA for the MWNTs compacts were found respectively significantly more
      than the increments of those for the GP compacts, suggesting that the larger
      amount of protein adsorbed on the MWNTs was crucial. More results showed that
      ALP/DNA and protein/DNA of the cells on the two kinds of compacts pre-soaked in
      culture medium having additional rhBMP-2 were both higher than those of the cells
      on the samples re-soaked in culture medium with 50% FBS, and that those values
      for the MWNTs compacts increased much more. Larger mineral content was found on
      the MWNTs compacts than on the GP compacts at day 7. In vivo experiment showed
      that the MWNTs could induce ectopic bone formation in the dorsal musculature of
      ddy mice while GP could not. The results indicated that MWNTs might stimulate
      inducible cells in soft tissues to form inductive bone by concentrating more
      proteins, including bone-inducing proteins.

PMID- 22483243
TI  - The stimulation of adipose-derived stem cell differentiation and mineralization
      by ordered rod-like fluorapatite coatings.
AB  - In this study, the effect of ordered rod-like FA coatings of metal discs on
      adipose-derived stem cell (ASC)'s growth, differentiation and mineralization was
      studied in vitro; and their mineral inductive effects in vivo. After 3 and 7
      days, the cell number on the metal surfaces was significantly higher than those
      on the ordered and disordered FA surfaces. However, after 4 weeks much greater
      amounts of mineral formation was induced on the two FA surfaces with and even
      without osteogenesis induction. The osteogenic profiles showed the up regulation
      of a set of pro-osteogenic transcripts and bone mineralization phenotypic markers
      when the ASCs were grown on FA surfaces compared to metal surfaces at 7 and 21
      days. In addition to BMP and TGFbeta signaling pathways, EGF and FGF pathways
      also appeared to be involved in ASC differentiation and mineralization. In vivo
      studies showed accelerated and enhanced mineralized tissue formation integrated
      within ordered FA coatings. After 5 weeks, over 80% of the ordered FA coating was
      integrated with a mineralized tissue layer covering the implants. Both the
      intrinsic properties of the FA crystals and the topography of the FA coating
      appeared to dominate the cell differentiation and mineralization process.

PMID- 22483244
TI  - Micropatterning of mammalian cells on inorganic-based nanosponges.
AB  - Developing artificial scaffolding structures in vitro in order to mimic
      physiological-relevant situations in vivo is critical in many biological and
      medical arenas including bone and cartilage generation, biomaterials, small-scale
      biomedical devices, tissue engineering, as well as the development of
      nanofabrication methods. We focus on using simple physical principles
      (photolithography) and chemical techniques (liquid vapor deposition) to build non
      cytotoxic scaffolds with a nanometer resolution through using silicon substrates
      as the backbone. This method merges an optics-based approach with chemical
      restructuring to modify the surface properties of an IC-compatible material,
      switching from hydrophilicity to hydrophobicity. Through this nanofabrication
      based approach that we developed, hydrophobic oxidized silicon nanosponges were
      obtained. We then probed cellular responses-examining cytoskeletal and
      morphological changes in living cells through a combination of fluorescence
      microscopy and scanning electron microscopy-via culturing Chinese hamster ovary
      cells, HIG-82 fibroblasts and Madin-Darby canine kidney cells on these silicon
      nanosponges. This study has demonstrated the potential applications of using
      these silicon-based nanopatterns such as influencing cellular behaviors at
      desired locations with a micro-/nanometer level.

PMID- 22483245
TI  - MRI-monitored long-term therapeutic hydrogel system for brain tumors without
      surgical resection.
AB  - To overcome the unresolved issues of conventional therapeutic approaches such as
      radiation therapy, chemotherapy, combinational chemotherapy, and surgical
      treatment, we designed an injectable 'MRI-monitored long-term therapeutic
      hydrogel (MLTH)' system as an alternative/adjuvant approach for brain tumors. The
      MLTH system consists of a thermosensitive/magnetic poly(organophosphazene)
      hydrogel (the magnetic hydrogel) as a biodegradable imaging platform and an
      anticancer drug as a therapeutic agent via a simple physical mixing. The MLTH
      system has adequate properties for the MRI-monitored long-term therapy as
      follows: injectability, localizability due to fast gelation at body temperature,
      biocompatibility, biodegradability, sustained drug release, and MR imaging
      function. Since the MLTH system only requires a very small-sized pin hole
      injected into the area of brain tumors stereotactically, we suggest that the MLTH
      system can be an alternative/adjuvant approach to treat the malignant brain
      tumors without any surgical resection. Furthermore, we expect that the MLTH
      system can minimize the side effects from either an intravenous injection or
      surgical operation because one of the aims of MLTH is to focus on the sustained
      local delivery of anticancer drugs via a one- or two-time intratumoral
      injections. Thus, we assessed successfully the MRI-monitored long-term
      therapeutic potentialities of the MLTH system for brain tumors and estimated the
      inhibition efficacy of tumor growth via an MRI-monitored long-term therapy in
      this study.

PMID- 22483246
TI  - Sustained delivery of SDF-1alpha from heparin-based hydrogels to attract
      circulating pro-angiogenic cells.
AB  - Enrichment of progenitor cells in ischemic tissue has become a promising
      therapeutic strategy in the treatment of myocardial infarction. Towards this aim,
      we report a biology-inspired concept using sulfated glycosaminoglycans to
      sustainably generate chemokine gradients for the localized accumulation of early
      endothelial progenitor cells (eEPCs). StarPEG-heparin hydrogels, which have been
      previously demonstrated to support angiogenesis, were functionalized with SDF
      1alpha, a potent chemoattractant known to act on EPCs. The gels were
      quantitatively shown to release the chemokine in amounts that are adjustable by
      the choice of loading concentrations and by matrix metalloprotease (MMP) mediated
      hydrogel cleavage. Transwell assays confirmed significantly enhanced migration of
      early EPCs towards concentration gradients of hydrogel-delivered SDF-1alpha in
      vitro. Subcutaneous implantation of SDF-1alpha-releasing gels in mice resulted in
      massive infiltration of early EPCs and subsequently improved vascularization. In
      conclusion, sustained delivery of SDF-1alpha from pro-angiogenic starPEG-heparin
      hydrogels can effectively attract early EPCs, offering a powerful means to
      trigger endogenous mechanisms of cardiac regeneration.

PMID- 22483247
TI  - Transoral laser microsurgery elevates fundamental frequency in early glottic
      cancer.
AB  - OBJECTIVE: To evaluate the long-term voice characteristics and quality of life of
      early glottic cancer patients after definitive treatment. STUDY DESIGN: Case
      series with chart review in a tertiary care medical center in Taiwan. METHODS:
      Forty-two consecutive patients who received radiation therapy (RT) or transoral
      laser microsurgery (TLM) for early glottic cancer over 12 months were evaluated
      for voice laboratory data and quality-of-life measurements. RESULTS: Twenty-four
      patients received RT, and 18 underwent TLM. There was no difference between the
      two groups on acoustic and aerodynamic voice measures except for modal
      fundamental frequency in males. In the Functional Assessment of Cancer Therapy
      Head and Neck survey, the TLM group had better communication than the RT group,
      but there were no differences in voice quality and strength. There was also no
      significant difference in the Voice Handicap Index 10 evaluation. CONCLUSIONS:
      Male patients who received TLM have higher modal fundamental frequency than male
      patients who received RT and norms. Voice-related life quality is similar in
      patients regardless of RT or TLM treatment for early glottic cancer, but those
      who receive TLM have better communication abilities than those who receive RT.

PMID- 22483248
TI  - Adiponectin and arterial stiffness in hypertensive patients.

PMID- 22483249
TI  - Takotsubo cardiomyopathy and left ventricular outflow tract obstruction during
      stress echocardiography: why the choice of stress modality matters.

PMID- 22483250
TI  - Documentation of impaired coronary blood flow by TIMI frame count method in
      patients with atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with impaired coronary flow
      and diminished myocardial perfusion. In the present study we aimed to evaluate
      coronary blood flow by means of Thrombolysis in Myocardial Infarction (TIMI)
      frame count (TFC) in patients with AF in the absence of obstructive coronary
      artery disease (CAD). METHODS: This prospective study initially enrolled 166
      patients with AF and 332 age- and gender-matched control subjects without AF.
      After diagnostic coronary angiography, TFC was assessed in the participants
      without obstructive CAD, with 146 in the AF group and 150 in the control group.
      RESULTS: The TFC for three major coronary arteries and the mean TFC were found to
      be significantly higher in AF patients compared to control subjects (34.1 +/-
      10.4 vs. 25.0 +/- 10.4, 31.8 +/- 9.7 vs. 23.7 +/- 9.1, and 32.3 +/- 9.5 vs. 24.1
      +/- 8.4 for each artery and 32.8 +/- 9.2 vs. 24.3 +/- 8.9 for mean TFC, p<0.001
      for all comparisons). The mean TFC was 28.8 +/- 7.9 in patients with paroxysmal
      AF, 33.7 +/- 8.7 in those with persistent AF, and 39.0 +/- 8.8 in those with long
      standing or permanent AF (p<0.01 for all comparisons). After multivariate
      analysis, we found that the presence of AF remains to be independently associated
      with mean TFC. In AF group, baseline heart rate, left ventricular ejection
      fraction, AF duration and left atrium diameter were found to be independently
      associated with mean TFC. CONCLUSIONS: Patients with atrial fibrillation in the
      absence of obstructive coronary artery disease have significantly higher TIMI
      frame counts for all three coronary vessels, indicating impaired coronary blood
      flow, compared to the control subjects without atrial fibrillation.

PMID- 22483251
TI  - Progression of aortic stenosis in elderly patients over long-term follow up.
AB  - BACKGROUND: The natural history of aortic stenosis (AS) in elderly patients
      remains poorly defined. In an elderly cohort over long-term follow-up, we
      assessed: 1) rates and predictors of hemodynamic progression and 2) composite
      aortic valve replacement (AVR) or death endpoint. METHODS: Consecutive Department
      of Veterans' Affairs patients with AS (>60 years) were prospectively enrolled
      between 1988 and 1994 (n=239) and followed until 2008. Patients with >= 2 trans
      thoracic echocardiograms >6 months apart were included in the progression
      analysis (n=147). Baseline demographics, comorbidities and echocardiography
      parameters were recorded. Follow-up was censored at AVR/death. RESULTS: The age
      of patients was 73 +/- 6 years; 82% were male. Baseline AS severity was mild
      (67%), moderate (23%) and severe (10%). Follow-up was 6.5 +/- 4 years (range: 1
      17 years). Annualized mean aortic valve gradient progression rates were: mild AS
      4 +/- 4 mmHg/year; moderate AS 6 +/- 5 mmHg/year and severe AS 10 +/- 8 mmHg/year
      (p<0.001). Five-year event-free survival was 66 +/- 5%, 23 +/- 7% and 20 +/- 10%
      for mild, moderate and severe AS respectively. Progression to severe AS occurred
      in 35% and 74% of patients with mild and moderate AS respectively. Independent
      predictors of rapid progression were: baseline AS severity (per grade) (OR 2.6,
      p=0.001), aortic valve calcification (per grade) (OR 2.1, p=0.01), severe renal
      impairment (OR 4.0, p=0.04) and anemia (OR 2.3, p=0.05). CONCLUSIONS: In elderly
      patients, hemodynamic progression of AS is predicted by AS severity, renal
      function, aortic valve calcification and history of anemia. These factors
      identify patients at high risk of rapid hemodynamic progression, for whom more
      frequent clinical and echocardiographic surveillance is advisable.

PMID- 22483252
TI  - A general theory of acute and chronic heart failure.
AB  - Current concepts of heart failure propose multiple heterogeneous
      pathophysiological mechanisms. Recently a theoretical framework for understanding
      chronic heart failure was suggested. This paper develops this framework to
      include acute heart failure syndromes. We propose that all acute heart failure
      syndromes may be understood in terms of a relative fall in left ventricular
      stroke volume. The initial compensatory mechanism is frequently a tachycardia
      often resulting in a near normal cardiac output. In more severe forms a fall in
      cardiac output causes hypotension or cardiogenic shock. In chronic heart failure
      the stroke volume and cardiac output is returned to normal predominantly through
      ventricular remodeling or dilatation. Ejection fraction is simply the ratio of
      stroke volume and end-diastolic volume. The resting stroke volume is
      predetermined by the tissue's needs; therefore, if the ejection fraction changes,
      the end-diastolic volume must change in a reciprocal manner. The potential role
      of the right heart in influencing the presentation of left heart disease is
      examined. We propose that acute pulmonary edema occurs when the right ventricular
      stroke volume exceeds left ventricular stroke volume leading to fluid
      accumulation in the alveoli. The possible role of the right heart in determining
      pulmonary hypertension and raised filling pressures in left-sided heart disease
      are discussed. Different clinical scenarios are presented to help clarify these
      proposed mechanisms and the clinical implications of these theories are
      discussed. Finally an alternative definition of heart failure is proposed.

PMID- 22483253
TI  - Body mass index is related to the perception of exertional breathlessness in
      patients presenting with dyspnoea of unknown origin.

PMID- 22483254
TI  - The missing link between heart failure and sleep disordered breathing: increased
      left ventricular wall stress.

PMID- 22483255
TI  - Optical coherence tomography assessment of early stent strut coverage in patients
      treated with a thin-strut bare cobalt-chromium stent coated with silicon carbide.

PMID- 22483256
TI  - Paced patient and acute myocardial infarction.

PMID- 22483257
TI  - Fibrinogen and carotid intima media thickness determine fibrin density in
      different atherosclerosis extents.

PMID- 22483258
TI  - Contrasting effects of aliskiren versus losartan on hypertensive vascular
      remodeling.
AB  - BACKGROUND: Hyperactivation of the renin-angiotensin system contributes to
      hypertension-induced upregulation of vascular matrix metalloproteinases (MMPs)
      and remodeling, especially in the two kidney, one clip (2K1C) hypertension model.
      We hypothesized that the AT1R antagonist losartan or the renin inhibitor
      aliskiren, given at doses allowing similar antihypertensive effects, could
      prevent in vivo vascular MMPs upregulation and remodeling, and collagen/elastin
      deposition found in 2K1C hypertension by preventing the activation of
      extracellular signal-regulated kinase 1/2 (ERK 1/2) and transforming growth
      factor-beta1 (TGF-beta1). We also hypothesized that aliskiren could enhance the
      effects of losartan. METHODS: 2K1C rats were treated with aliskiren (50mg.kg(
      1).day(-1)), or losartan (10mg.kg(-1).day(-1)), or both by gavage during 4 weeks.
      RESULTS: Aliskiren, losartan, or both drugs exerted similar antihypertensive
      effects when compared with 2K-1C rats treated with water. Aliskiren reduced
      plasma renin activity in both sham and 2K-1C rats. Losartan alone or combined
      with aliskiren, but not aliskiren alone, abolished 2K1C-induced aortic
      hypertrophy and hyperplasia, and prevented the increases in aortic
      collagen/elastin content, MMP-2 levels, gelatinolytic activity, and expression of
      phospho-ERK 1/2 and TGF-beta1. No significant differences were found in the
      aortic expression of the (pro)renin receptor. CONCLUSIONS: These findings show
      that although losartan and aliskiren exerted similar antihypertensive effects,
      only losartan prevented the activation of vascular profibrotic mechanisms and MMP
      upregulation associated with vascular remodeling in 2K1C hypertension. Our
      findings also suggest that aliskiren does not enhance the protective effects
      exerted by losartan.

PMID- 22483259
TI  - Subclinical and clinical presentation of Kounis syndrome: another cause of
      troponin elevation?

PMID- 22483260
TI  - Increased serum angiopoietin-2 is associated with abdominal aortic aneurysm
      prevalence and cardiovascular mortality in older men.
AB  - BACKGROUND: Angiopoietin-2 (Angpt2) has been implicated in the mediation and
      regulation of angiogenesis and inflammation which are believed to be critical
      mechanisms in the pathogenesis of both abdominal aortic aneurysm (AAA) and
      cardiovascular events. The aim of this study was to assess whether serum Angpt2
      was associated with the prevalence of AAA and the occurrence of cardiovascular
      mortality in older men. METHODS: A cohort of 997 elderly men was recruited in
      1996-99. Aortic ultrasound identified an AAA in 308 (31%). In 2001-04, blood was
      collected and serum Angpt2 later measured by immunoassay. The association of
      Angpt2 with AAA was assessed using multiple regression analysis. All men were
      followed by means of the Western Australia Data Linkage System until July 31st
      2009. The association of Angpt2 with cardiovascular mortality was assessed using
      Cox proportional hazard analysis. RESULTS: Median serum Angpt2 was significantly
      higher (3.16 ng/ml, inter-quartile range 2.51-4.54) in men with AAA compared with
      men without AAA (2.70 ng/ml, inter-quartile range 2.03-3.72; p<0.001). After
      adjusting for cardiovascular risk factors, men with serum Angpt2 in the highest
      quartile (>3.95 ng/ml) had a 2.57-fold (95% CI 1.66-3.97, p<0.001) increased odds
      of AAA and a 4.12-fold (95% CI 1.90-8.94, p<0.001) increased relative risk of
      cardiovascular mortality compared to men with serum Angpt2 in the lowest quartile
      (<2.13 ng/ml). CONCLUSIONS: Serum Angpt2 is elevated in men with AAA and
      associated with an increased risk of cardiovascular mortality in older men.

PMID- 22483261
TI  - Type 2 diabetes and the progression of visualized atherosclerosis to clinical
      cardiovascular events.
AB  - BACKGROUND/OBJECTIVES: We prospectively evaluated to what extent pre-existing
      coronary artery disease (CAD) accounts for the increased vascular event risk of
      patients with type 2 diabetes (T2DM). METHODS: Vascular events were recorded over
      8 years in 750 consecutive patients whose baseline CAD state was verified
      angiographically. RESULTS: The baseline prevalence of CAD (87.8% vs. 80.4%;
      p=0.029) and of significant coronary stenoses >= 50% (69.5% vs. 58.4%; p=0.010)
      as well as the extent of CAD, i.e. the number of significant coronary stenoses
      (1.7 +/- 1.6 vs. 1.4 +/- 1.5; p=0.014) was higher in patients with T2DM (n=164)
      than in non-diabetic subjects. During follow-up, T2DM predicted vascular events
      (n=257) independently from the presence and extent of baseline CAD (HR 1.36 [1.03
      1.81]; p=0.032); conversely, the presence and extent of baseline CAD predicted
      vascular events independently from T2DM (HRs 3.29 [1.93-5.64]; p<0.001 and 1.37
      [1.23-1.53]; p<0.001, respectively). The relative risk increase conferred by T2DM
      was not significantly modulated by the presence of baseline CAD
      (p(interaction)=0.415). However, in absolute terms the risk increase conferred by
      T2DM was driven by an extremely high 53.5% event rate of patients with both T2DM
      and significant CAD at baseline; individuals with T2DM but without significant
      baseline CAD showed a significantly lower event rate (22.0%; p<0.001).
      CONCLUSIONS: T2DM and angiographically visualized coronary atherosclerosis are
      mutually independent predictors of vascular events. The overall risk increase
      conferred by T2DM is driven by accelerated progression of pre-existing
      atherosclerosis to clinical cardiovascular events; vascular risk is much lower in
      diabetic patients without pre-existing significant CAD.

PMID- 22483262
TI  - Membrane materials for addressing energy and environmental challenges.
AB  - Our modern society must solve various severe problems to maintain and increase
      our quality of life: from water stress to global warming, to fossil fuel
      depletion, to environmental pollution. The process intensification (PI) strategy
      is expected to contribute to overcoming many of these issues by facilitating the
      transition from a resource-intensive to a knowledge-intensive industrial system
      that will guarantee sustainable growth. Membrane operations, which respond
      efficiently to the requirements of the PI strategy, have the potential to replace
      conventional energy-intensive separation techniques, which will boost the
      efficiency and reduce the environmental impact of separations as well as
      conversion processes. This work critically reviews the current status and
      emerging applications of (integrated) membrane operations with a special focus on
      energy and environmental applications.

PMID- 22483263
TI  - Density of states-based molecular simulations.
AB  - One of the central problems in statistical mechanics is that of finding the
      density of states of a system. Knowledge of the density of states of a system is
      equivalent to knowledge of its fundamental equation, from which all thermodynamic
      quantities can be obtained. Over the past several years molecular simulations
      have made considerable strides in their ability to determine the density of
      states of complex fluids and materials. In this review we discuss some of the
      more promising approaches proposed in the recent literature along with their
      advantages and limitations.

PMID- 22483264
TI  - Experimental methods for phase equilibria at high pressures.
AB  - Knowledge of high-pressure phase equilibria is crucial in many fields, e.g., for
      the design and optimization of high-pressure chemical and separation processes,
      carbon capture and storage, hydrate formation, applications of ionic liquids, and
      geological processes. This review presents the variety of methods to measure
      phase equilibria at high pressures and, following a classification, discusses the
      measurement principles, advantages, challenges, and error sources. Examples of
      application areas are given. A detailed knowledge and understanding of the
      different methods is fundamental not only for choosing the most suitable method
      for a certain task but also for the evaluation of experimental data. The
      discrepancy between the (sometimes low) true accuracy of published experimental
      data and the (high) accuracy claimed by authors is addressed. Some essential
      requirements for the generation of valuable experimental results are summarized.

PMID- 22483265
TI  - Electrochemistry of mixed oxygen ion and electron conducting electrodes in solid
      electrolyte cells.
AB  - Mixed ion and electron conductors (MIECs) have garnered increased attention as
      active components in the electrodes of solid oxide electrolyzers (for electricity
      to fuel conversion) and especially of solid oxide fuel cells (for fuel to
      electricity conversion). Although much of the work in the literature is directed
      toward the understanding of oxygen electroreduction on the surfaces of MIECs,
      more recent studies also explore the role of these materials in fuel
      electrooxidation. In both cases, the rich chemical and electronic behaviors of
      MIECs imply a broad range of possible reaction pathways. We highlight the
      significant progress that has been made in elucidating these pathways through
      well-designed experimental and computational studies. At the macroscopic level,
      patterned electrode studies enable identification of active sites, whereas at the
      microscopic level, surface-sensitive techniques in combination with atomistic
      level simulations are beginning to reveal the nature of the rate-determining
      step(s) and enable rational design of materials with enhanced activity.

PMID- 22483266
TI  - Incarvilleatone, a new cyclohexylethanoid dimer from Incarvillea younghusbandii
      and its inhibition against nitric oxide (NO) release.
AB  - Incarvilleatone (1), an unprecedented dimeric cyclohexylethanoid analog with a
      racemic nature, was isolated from the whole plant of Incarvillea younghusbandii.
      HPLC chiral separation of 1 gave two enantiomers (-)-incarvilleatone and (+)
      incarvilleatone. The structure of 1 was established by spectroscopic methods and
      single crystal X-ray diffraction. The absolute configurations of enantiomers were
      determined by quantum mechanical calculation. (-)-Incarvilleatone exhibited a
      potent inhibitory effect against NO production in LPS-induced RAW264.7
      macrophages.

PMID- 22483267
TI  - Mining and modeling human genetics for autism therapeutics.
AB  - A growing understanding of the genetic origins of autism spectrum disorders
      (ASDs) and the impact of ASD risk genes on synaptic function presents new
      opportunities for drug discovery. Large-scale human genetics studies have begun
      to reveal molecular pathways and potential therapeutic drug targets. Subsequent
      validation and characterization of ASD risk genes in mouse models holds promise
      for defining relevant cellular mechanisms and brain circuits associated with the
      core behavioral symptoms of autism. Here we review recent advances in the
      molecular therapeutics in ASDs and discuss opportunities and obstacles for
      converting emerging biology into new medicines. We present emerging concepts on
      the impact of risk genes during development and adulthood that define points of
      intervention. We further highlight ongoing clinical trials in patients with
      syndromic forms of autism. These clinical studies will be an important test of
      the utility of human genetics as a starting point for drug discovery in ASDs.

PMID- 22483268
TI  - Valveless gated injection for microfluidic chip-based liquid chromatography
      system with polymer monolithic column.
AB  - In this work, we developed a microfluidic chip-based liquid chromatography (LC)
      system with valveless gated sample injection method and monolithic columns. The
      valveless LC system consisted of a microchip with a separation column and a
      balance column, two syringe pumps and a laser induced fluorescence detector.
      Nanoliter-scale sample injection was achieved by simply switching the ON and OFF
      states of the syringe pumps under gated injection mode, without the need of any
      mechanical valve. The balance column facilitated the gated injection process by
      balancing the back pressure in the sample channel with that in the separation
      channel. Under the gated injection mode, the sample injection volumes could be
      varied in the range of 0.4-2.4 nL. We investigated the effects of the mobile
      phase composition, flow rate, and the sample injection volume on the performance
      of the LC system. Under the optimized conditions, two fluorescently labeled
      amines were successfully separated in less than 220 s with a column length of
      1cm. Theoretical plates ranging from 35,700 to 29,400 per meter, corresponding to
      plate heights ranging from 28 to 34 MUm were obtained. The advantages of the
      present system include simple system structure, ease of operation, convenience
      for varying injection volume, and high sample loading capacity.

PMID- 22483269
TI  - A novel headspace gas chromatographic method for in situ monitoring of monomer
      conversion during polymerization in an emulsion environment.
AB  - This paper describes a novel multiple-headspace extraction/gas chromatographic
      (MHE-GC) technique for monitoring monomer conversion during a polymerization
      reaction in a water-based emulsion environment. The polymerization reaction of
      methyl methacrylate (MMA) in an aqueous emulsion is used as an example. The
      reaction was performed in a closed headspace sample vial (as a mini-reactor),
      with pentane as a tracer. In situ monitoring of the vapor concentration of the
      tracer, employing a multiple headspace extraction (sampling) scheme, coupled to a
      GC, makes it possible to quantitatively follow the conversion of MMA during the
      early stages of polymerization. Data on the integrated amount of the tracer vapor
      released from the monomer droplet phase during the polymerization is described by
      a mathematic equation from which the monomer conversion can be calculated. The
      present method is simple, automated and economical, and provides an efficient
      tool in the investigation of the reaction kinetics and effects of the reaction
      conditions on the early stage of polymerization.

PMID- 22483270
TI  - Synthesis and antibacterial activity against ralstonia solanacearum for novel
      hydrazone derivatives containing a pyridine moiety.
AB  - BACKGROUND: Ralstonia solanacearum, one of the most important bacterial diseases
      on plants, is a devastating, soil-borne plant pathogen with a global distribution
      and an unusually wide host range. In order to discover new bioactive molecules
      and pesticides acting on tobacco bacterial wilt, we sought to combine the active
      structure of hydrazone and pyridine together to design and synthesize a series of
      novel hydrazone derivatives containing a pyridine moiety. RESULTS: A series of
      hydrazone derivatives containing a pyridine moiety were synthesized. Their
      structures were characterized by 1 H-NMR, 13 C-NMR, IR, and elemental analysis.
      The preliminary biological activity tests showed that compound 3e and 3g
      exhibited more than 80% activity against Ralstonia solanacearum at 500 mg/L,
      especially compound 3g displayed relatively good activity to reach 57.0% at 200
      mg/L. CONCLUSION: A practical synthetic route to hydrazone derivatives containing
      a pyridine moiety by the reaction of intermediates 2 with different aldehydes in
      ethanol at room temperature using 2-chloronicotinic acid and 2-amino-5-chloro-3
      methylbenzoic acid as start materials is presented. This study suggests that the
      hydrazone derivatives containing a substituted pyridine ring could inhibit the
      growth of Ralstonia solanacearum.

PMID- 22483271
TI  - The blood-brain barrier choline transporter.
AB  - Drug delivery to the brain is made difficult by the blood-brain barrier (BBB)
      which is selectively permeable to organic drug compounds. Several membrane solute
      and nutrient transporters are expressed in the BBB vasculature, which may be
      utilized as mechanism of delivery of drugs to the brain. Of interest to us, are
      the organic cation transporters which could be used to transport cationic
      compounds into the CNS. In this mini-review, we will review the current
      understanding of the structural requirements for designing compounds which could
      effectively use organic cation transporters (OCT). For the first time, structural
      requirements for both OCT1 and OCT2 versus the BBB choline transporter (BBBCHT)
      are discussed and compared. The information gained here could increase the
      success rate in successful CNS drug delivery and therapeutics.

PMID- 22483272
TI  - The ubiquitous choline transporter SLC44A1.
AB  - Choline is a zwitter ion that is positively charged at certain pH, which
      necessitates transport systems to allow this amine to cross the phospholipid
      bilayer of cellular membranes. The solute carrier 44A1 (SLC44A1), also referred
      to as choline transporter-like protein 1 (CTL1), is a recently discovered choline
      transporter with an intermediate affinity for choline; this transport is Na(+)
      independent and sensitive to inhibition by the drug hemicholinium-3. We highlight
      in this review the discovery and characterization of SLC44A1, describe its
      expression patterns and subcellular localization, and summarize evidence for the
      role of this choline transporter in the central nervous system.

PMID- 22483273
TI  - Choline transporter CHT regulation and function in cholinergic neurons.
AB  - Choline uptake into cholinergic nerve terminals by the sodium-dependent high
      affinity choline transporter CHT is essential for providing choline as substrate
      for synthesis of acetylcholine (ACh); ACh is used by cholinergic neurons to
      communicate information to a wide range of tissues in central and peripheral
      nervous systems. CHT is expressed almost exclusively in cholinergic neurons, and
      is subject to transcriptional and post-translational control by factors that
      promote or diminish cholinergic neurotransmission. The distribution of CHT
      proteins within cholinergic presynaptic terminals is dynamically regulated. Thus,
      choline uptake activity is determined largely by the plasma membrane CHT level,
      and this is finely controlled by a balance between internalization and recycling
      of CHT proteins in endosomal compartments. CHT proteins are also in synaptic
      vesicle membranes, thereby allowing cell surface CHT levels to increase rapidly
      in conjunction with exocytotic transmitter release to provide enhanced choline
      for ACh re-synthesis. Little is known about post-translational modification of
      CHT, although data is emerging that CHT activity and subcellular trafficking is
      modulated by kinase-mediated phosphorylation. Recent studies have also identified
      proteins with which CHT interacts, but this requires further investigation to
      reveal the role of other proteins in regulating CHT function and activity.
      Polymorphisms in CHT protein and modifications in its expression are linked to
      neurological and psychiatric disorders, and can alter function of peripheral
      systems that are regulated by cholinergic innervation, such as the cardiovascular
      system. The critical role of CHT in maintaining cholinergic transmission
      indicates that it could be a target for therapeutic intervention to promote ACh
      synthesis, but mechanisms by which this can be accomplished have not been
      adequately addressed.

PMID- 22483274
TI  - An introduction to the nutrition and metabolism of choline.
AB  - Choline is a ubiquitous water soluble nutrient, often associated with the B
      vitamins; however, not yet officially defined as a B vitamin. It is important in
      the synthesis of phospholipid components of cell membranes, and plasma
      lipoproteins, providing structural integrity as well as being important in cell
      signaling; it is also important in the synthesis of the neurotransmitter
      acetylcholine, and the oxidized form of choline, glycine betaine, serves as an
      important methyl donor in the methionine cycle. It is present in a wide variety
      of foods, and is endogenously synthesized in humans through the sequential
      methylation of phosphatidylethanolamine. The present article represents an
      introduction to the nutrition, metabolism, and physiological functions of choline
      and choline derivatives in humans. The association of choline and choline
      derivatives in risk of chronic disease, including: neural tube defects, coronary
      artery disease, cancer, Alzheimer's disease, dementia, and memory, and cystic
      fibrosis is reviewed.

PMID- 22483276
TI  - Interplay of maternal care and genetic influences in programming adult
      hippocampal neurogenesis.
AB  - BACKGROUND: Adult hippocampal neurogenesis, which is involved in the
      physiopathology of hippocampal functions, is genetically determined and
      influenced by early life events. However, studies on the interaction of these
      determining forces are lacking. This prompted us to investigate whether adult
      hippocampal neurogenesis can be modulated by maternal care and whether this
      influence depends upon the genetic background of the individual. METHODS: We used
      a model of fostering that allows singling out the influence of the genetic make
      up of the pups on the outcome of maternal behavior. Mice from two different
      inbred strains (C57BL/6J and DBA/2J) known to differ in their baseline
      neurogenesis as well as in their sensitivity to the influence of environmental
      experiences were raised by nonrelated mothers from the AKR/Ola (AKR) and C3H/He
      (C3H) strains exhibiting low- and high-pup-oriented behavior, respectively.
      Neurogenesis was then assessed in the dentate gyrus of the adult adopted C57BL/6J
      and DBA/2J mice. RESULTS: We show that both the number and the morphological
      features of newborn granule cells in the dentate gyrus are determined by the
      maternal environment to which mice were exposed as pups and that this sensitivity
      to maternal environment is observed only in genetically vulnerable subjects.
      CONCLUSIONS: Altogether, our data indicate interplay between early environment
      and the genetic envelop of an individual in determining adult hippocampal
      neurogenesis. Our experimental approach could thus contribute to the
      identification of factors determining the neurogenic potential of the adult
      hippocampus.

PMID- 22483277
TI  - Genomics and genetics of human and primate y chromosomes.
AB  - In mammals, the Y chromosome plays the pivotal role in male sex determination and
      is essential for normal sperm production. Yet only three Y chromosomes have been
      completely sequenced to date--those of human, chimpanzee, and rhesus macaque.
      While Y chromosomes are notoriously difficult to sequence owing to their highly
      repetitive genomic landscapes, these dedicated sequencing efforts have generated
      tremendous yields in medical, biological, and evolutionary insight. Knowledge of
      the complex structural organization of the human Y chromosome and a complete
      catalog of its gene content have provided a deeper understanding of the
      mechanisms that generate disease-causing mutations and large-scale
      rearrangements. Variation among human Y-chromosome sequences has been an
      invaluable tool for understanding relationships among human populations.
      Comprehensive comparisons of the human Y-chromosome sequence with those of other
      primates have illuminated aspects of Y-chromosome evolutionary dynamics over much
      longer timescales (>25 million years compared with 100,000 years). The future
      sequencing of additional Y chromosomes will provide a basis for a more
      comprehensive understanding of the evolution of Y chromosomes and their roles in
      reproductive biology.

PMID- 22483278
TI  - The kinetics of non-synaptically triggered acute excitotoxic responses in the
      central nervous system observed using intrinsic optical signals.
AB  - BACKGROUND AND PURPOSE: Excitotoxic central nervous system (CNS) response is
      believed to be important in the pathophysiology of irreversible sequelae of
      anoxia and brain trauma. Furthermore, the sodium pump has been associated with
      functional CNS syndromes such as migraine and epilepsy. Thus, a detailed
      description of the kinetics of excitotoxic responses elicited by glutamatergic
      pathway activation and sodium pump blockade can be useful in pre-clinical
      research. This should be aimed at minimizing the brain damage due to anoxia or
      trauma or the prophylaxis of functional syndromes. EXPERIMENTAL APPROACH: The
      kinetics of the intrinsic optical signals of excitotoxic responses were examined
      in detail following N-methyl-D-aspartic acid or ouabain extrinsic pulses in in
      vitro retinas and compared to optical profiles of retinal spreading depression
      waves in intact retinae in chicken eye-cups. Additional experiments recorded
      field potentials simultaneously with the intrinsic optical signals. The
      protective effects of extracellular magnesium and glutathione were also examined.
      RESULTS: The initial phase (10 min) of the excitotoxic responses were very
      similar, however the final outcome was different: usually, irreversible damage
      was restricted to patches of tissue following N-methyl-D-aspartic acid pulses. By
      contrast, extrinsic ouabain experiments resulted in whole tissue death even with
      concentrations as low as 10 nM, except in three experiments in which glutathione
      at physiological concentrations was added to the perfusion 60 min before the
      pulse. CONCLUSION: the glial sodium pump must be a receptor of endogenous cardiac
      glycosides and its blockade can trigger excitotoxicity with a non-synaptic
      mechanism. The demonstration of glutathione protective effect suggests the
      importance of the transducer role of this membrane ATPase in the CNS.

PMID- 22483279
TI  - Editorial: COMT as a drug target for nervous system disorders.

PMID- 22483275
TI  - Choline nutrition programs brain development via DNA and histone methylation.
AB  - Choline is an essential nutrient for humans. Metabolically choline is used for
      the synthesis of membrane phospholipids (e.g. phosphatidylcholine), as a
      precursor of the neurotransmitter acetylcholine, and, following oxidation to
      betaine, choline functions as a methyl group donor in a pathway that produces S
      adenosylmethionine. As a methyl donor choline influences DNA and histone
      methylation--two central epigenomic processes that regulate gene expression.
      Because the fetus and neonate have high demands for choline, its dietary intake
      during pregnancy and lactation is particularly important for normal development
      of the offspring. Studies in rodents have shown that high choline intake during
      gestation improves cognitive function in adulthood and prevents memory decline
      associated with old age. These behavioral changes are accompanied by
      electrophysiological, neuroanatomical, and neurochemical changes and by altered
      patterns of expression of multiple cortical and hippocampal genes including those
      encoding key proteins that contribute to the biochemical mechanisms of learning
      and memory. These actions of choline are observed long after the exposure to the
      nutrient ended (months) and correlate with fetal hepatic and cerebral cortical
      choline-evoked changes in global- and gene-specific DNA cytosine methylation and
      with dramatic changes of the methylation pattern of lysine residues 4, 9 and 27
      of histone H3. Moreover, gestational choline modulates the expression of DNA
      (Dnmt1, Dnmt3a) and histone (G9a/Ehmt2/Kmt1c, Suv39h1/Kmt1a) methyltransferases.
      In addition to the central role of DNA and histone methylation in brain
      development, these processes are highly dynamic in adult brain, modulate the
      expression of genes critical for synaptic plasticity, and are involved in
      mechanisms of learning and memory. A recent study documented that in a cohort of
      normal elderly people, verbal and visual memory function correlated positively
      with the amount of dietary choline consumption. It will be important to determine
      if these actions of choline on human cognition are mediated by epigenomic
      mechanisms or by its influence on acetylcholine or phospholipid synthesis.

PMID- 22483280
TI  - Suggestion and pain in migraine: a study by laser evoked potentials.
AB  - Belief and expectation are part of placebo effect. Migraine patients are
      characterized by a dysfunctional modulation of pain processing, though a clear
      placebo effect emerges in clinical trials. The aim of the study was to evaluate
      the effect of visual and verbal suggestion on subjective pain sensation and
      cortical responses evoked by CO2 painful laser stimuli in migraine without aura
      patients vs healthy controls. Twenty-six patients were recorded during the inter
      ictal phase and compared to 26 sex and age-matched controls. The right hand and
      the right supraorbital zone were stimulated during a not conditioned and a
      conditioned task, where laser stimuli were delivered after a verbal and visual
      cues of decreased (D), increased (I) or basal (B) intensity, which was left
      unmodified during the entire task. In control subjects pain rating changed,
      according to the announced intensity, while in migraine patients the basal hyper
      algesia remained unmodified. The N1 and N2 amplitudes tended to change coherently
      with the stimulus cue in controls, while an opposite paradoxical increase in
      decreasing condition emerged in migraine. The P2 amplitude modulation was also
      reduced in migraine, differently from controls. The altered pattern of pain
      rating and N2 amplitude modulation concurred with frequency of migraine,
      disability and allodynia. In controls suggestion influenced cortical pain
      processing and subjective pain rating, while in migraine a peculiar pattern of
      cortical activation contrasted external cues in order to maintain the basal hyper
      algesia. This scarce influence of induced suggestion on pain experience seemed to
      characterize patients with more severe migraine and central sensitization.

PMID- 22483281
TI  - Tension arachnoid cyst causing uncal herniation in a 60 year old: a rare
      presentation.
AB  - Arachnoid cysts are congenital benign cysts accounting for approximately 1% of
      all intracranial mass lesions. Uncal herniation due to arachnoid cyst is a rare
      mode of presentation. It is hypothesized that only tension arachnoid cyst could
      cause the life-threatening condition that results from a progressive
      deterioration and worsening of a simple and usually congenital arachnoid cyst,
      associated with the formation of a "ball valve" at the point of an opening on the
      cyst wall. To-date only one case of an arachnoid cyst causing Uncal herniation
      has been reported to the best of our knowledge. We present a rare case of uncal
      herniation in a 60-year-old lady caused by a giant left temporal arachnoid cyst.
      She presented to us in emergency room after experiencing headaches since last one
      week followed by vomiting, seizures, and altered state of consciousness. She was
      operated immediately and marsupialization of the arachnoid cyst was performed.
      She showed good recovery. Although arachnoid cyst is a benign slowly growing
      pathology, it can lead to Uncal herniation as a "tension" arachnoid cyst,
      possible due to "ball-valve" mechanism. Elective treatment should be considered
      to prevent progressive significant enlargement of cyst.

PMID- 22483282
TI  - Molecular interaction of the antineoplastic drug, methotrexate with human brain
      acetylcholinesterase: a docking study.
AB  - This study describes molecular interactions between human brain
      acetylcholinesterase (AChE) and the well known anti-neoplastic drug, methotrexate
      (MTX) and its comparison to 'AChE-cyclophosphamide (CP) interactions' that we
      reported previously. Docking between MTX and AChE was performed using
      'Autodock4.2'. Hydrophobic interactions and hydrogen bonds both play an equally
      important role in the correct positioning of MTX within the 'acyl pocket' as well
      as 'catalytic site' of AChE to permit docking. However, docking of CP to AChE is
      largely dominated by hydrophobic interactions. Such information may aid in the
      design of versatile AChE-inhibitors, and is expected to aid in safe clinical use
      of MTX. Scope still remains in the determination of the three-dimensional
      structure of AChE-MTX complex by X-ray crystallography to validate the described
      data. The current computational study supports our previous experimental study
      which concluded a mixed inhibition model for AChE-inhibition by MTX. Furthermore,
      the present report confirms that MTX is a more efficient inhibitor of human brain
      AChE compared to CP with reference to K(i) and DeltaG values.

PMID- 22483283
TI  - Changes in cannabinoid receptor subtype 1 activity and interaction with
      metabotropic glutamate subtype 5 receptors in the periaqueductal gray-rostral
      ventromedial medulla pathway in a rodent neuropathic pain model.
AB  - This study analyzed the effect of intra-ventrolateral periaqueductal grey (VL
      PAG) cannabinoid receptor (CB) stimulation on pain responses and rostral
      ventromedial medulla (RVM) neural activity in the chronic constriction injury
      (CCI) model of neuropathic pain in rats. Interaction between CB1 and metabotropic
      glutamate 1 and 5 (mGlu(1)/mGlu(5)) receptors was also investigated together with
      the expression of the CB1 receptor associated Galphai3 and cannabinoid receptor
      interacting 1a (CRIP 1a) proteins and the endocannabinoid synthesising and
      hydrolysing enzymes. In rats not subjected to CCI-induced pain, intra-VL PAG (R)
      (+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4
      benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) (2-4-8 nmol), a
      CB receptor agonist, increased the tail flick latency and changed the ongoing
      activity of RVM OFF and the tail flick-related activity of the ON and OFF cells,
      accordingly. These effects were prevented by SR141716A and MPEP, selective CB(1)
      and mGlu(5) receptor antagonists, respectively, though not by CPCCOEt, a
      selective mGlu(1) receptor antagonist. A higher dose up to 16 nmol of WIN 55,212
      2 was necessary to increase tail flick latency and change ON and OFF cell
      activity in CCI rats. Consistently, CCI rats showed a decrease in the expression
      of CB(1) receptors, NAPE-PLD, Galphai3 and CRIP 1a proteins;the expression of
      diacylglycerol lipase A (DAGLA) was increased while fatty acid amide hydrolase
      (FAAH) and monoacylglycerol lipase (MGL) did not change. As in control rats, MPEP
      and SR141716A also blocked WIN 55,212-2- induced effects in CCI rats. These data
      demonstrate a down regulation of the endocannabinoid system and a functional
      interaction between mGlu(5) and CB(1) receptors for cannabinoid-mediated effect
      in the PAG-RVM pain circuitry in neuropathic pain inflicted rats.

PMID- 22483284
TI  - SNP-mediated neuroprotection under glucose deprivation is enhanced by Hypericum
      perforatum.
AB  - Hypericum perforatum is a medicinal herb possessing ability for protecting
      neurons from oxidative stress. Since nitric oxide (NO) may be protective against
      oxidative stress-induced cell death as occurs in glucose deprivation (GD)-induced
      neurotoxicity, whether a standardized extract of H. perforatum (HP) increases the
      NO-mediated neuroprotective effect in GD-PC12 cells was investigated. Induced
      death in PC12 cells by GD exposure for 18 h was partially prevented by cell
      incubation with sodium nitroprusside (SNP), a NO-donor. SNP increased survival
      and nitrite production in GD-cells in a concentration-dependent manner. Co
      incubation of cells with 10 MUM SNP plus 50-100 MUg/ml HP under GD insult
      significantly prevented GD-induced cell death to a higher extent than SNP alone
      as shown by an augmentation of cell survival and intracellular bcl-2 levels and a
      decrease of lipid peroxidation, caspase-3 activation and PARP cleavage.
      Cytoprotection by the NO-donor was almost abolished by the use of a NO scavenger
      and potentiated by the presence of superoxide dismutase. SNP and/or HP
      neuroprotection on GD-cells was significantly reversed by rotenone treatment.
      These results suggest that: (1) SNP could protect PC12 cells from GD-induced
      cytotoxicity through NO generation and (2) the enhancement of the SNP-mediated
      neuroprotective effect on GD-cells by HP might arise in part through scavenging
      of reactive oxygen species (ROS) and inhibition of mitochondrial dysfunction
      associated with the hypoglycemic episode. This current finding might highlight
      the development of therapeutic strategies aimed at manipulating NO-donors in
      combination with herb supplements containing ROS scavenger compounds for
      prophylaxis from brain ischemia.

PMID- 22483285
TI  - Targeting alpha-synuclein for the treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized as a neurodegenerative movement
      disorder presenting with rigidity, resting tremor, disturbances in balance and
      slowness in movement. An important pathologic feature of PD is the presence of
      Lewy bodies. The primary structural component of Lewy bodies are fibrils composed
      primarily of alpha-synuclein, a highly conserved 140 amino acid protein that is
      predominantly expressed in neurons and which may play a role in synaptic
      plasticity and neurotransmission. Numerous studies suggest the aggregation and
      modification of alpha-synuclein as a key step leading to Lewy body formation and
      neuronal cell loss associated with PD. Because of the central role of alpha
      synuclein in PD, it represents a novel drug target for the possible treatment of
      this disease. In this review, an overview of the role of alpha-synuclein in PD
      will be discussed with an emphasis on recent studies utilizing an immunization
      approach against alpha-synuclein as a possible treatment option for this
      debilitating disease.

PMID- 22483286
TI  - Melatonergic drugs for therapeutic use in insomnia and sleep disturbances of mood
      disorders.
AB  - Insomnia is common among elderly people and nearly 30 to 40% of the adult
      population also suffer from insomnia. Pharmacological treatment of insomnia
      include the use of benzodiazepine and non-benzodiazepine drugs like zolpidem,
      zaleplon, Zopiclone. Although these drugs improve sleep, their usage is also
      associated with number of adverse effects, Melatonin, the hormone secreted by the
      pineal gland of all animals and human beings has been used for treatment of
      insomnias, since the timing of its secretion in humans as well as in most of the
      animals coincides with the increase of nocturnal sleep propensity. Because of its
      short half life, melatonin slow release preparations were introduced for
      treatment of insomnia. Recently ramelteon, a selective MT1, MT2 receptor agonist
      with greater efficacy of action in treating insomnia has been used clinically and
      has been found effective in improving sleep quality, sleep efficacy and also in
      reducing the sleep onset time when compared to melatonin or slow melatonin
      preparations. The mechanism of action of ramelteon in improving sleep is
      discussed in the paper. Another melatonergic drug agomelatine besides acting on
      MT1/MT2 receptors also displays 5-HT2c antagonism and this drug has been found
      effective as a novel antidepressant for treating major depressive disorders.
      Agomelatine besides causing remission of depressive symptoms also improves sleep
      quality and efficiency. Other antidepressants depressants that are in clinical
      use today do not improve sleep. There are other melatonergic drugs like
      tasimelteon, 6-chloromelatonin. But ramelteon and agomelatine deserve special
      attention for treatment of insomnia and sleep disturbances associated with
      depressive disorders and have promising role for treatment of sleep disorders.

PMID- 22483287
TI  - Epigenetic mechanisms: targets for treatment of alcohol dependence and drug
      addiction.

PMID- 22483288
TI  - Multiple sclerosis update: hot topics from 5th joint triennial congress of the
      European and Americas Committees for Treatment and Research in Multiple Sclerosis
      (ECTRIMS/ACTRIMS).

PMID- 22483289
TI  - COMT implication in cognitive and psychiatric symptoms in chromosome 22q11
      microdeletion syndrome: a selective review.
AB  - 22q11.2 deletion syndrome (22q11DS) is a genetic syndrome associated with a
      microdeletion of the chromosome 22 band q11.2 with an estimated prevalence
      between 1:2,500 and 1:4,000. Studies of school-age children have shown that
      individuals with 22q11DS have high rates of psychiatric morbidity. In particular,
      by late adolescence, about 30% of patients with 22q11DS develop psychotic
      symptoms. One of the genes located in the microdeletion region of 22q11DS is the
      Catechol-O-Methyl transferase (COMT) which codes for an enzyme critically
      involved in the catabolic clearance of dopamine. COMT is critically involved in
      cognitive related disturbances, and it has often been suggested as a sensitive
      factor in the development of psychiatric disorders. Several studies have been
      conducted on the impact of COMT functional polymorphism in 22q11DS and its
      related cognitive/psychiatric correlates. In this review, we summarize mainly
      current knowledge on the correlation between schizophrenia/cognitive related
      symptoms and COMT genetic variations in 22q11DS. A selective literature review on
      this topic was undertaken. COMT might play an important role in modulating
      cognitive functions in 22q11DS but a clear relationship between COMT polimorphism
      and schizophrenia in 22q11DS need further investigation. Despite controversial
      results, 22q11DS represent a powerful model for studying the role of COMT and
      other genetic variations in schizophrenia. This is due to high risk in 22qDS
      patients of developing this disorder and their relative genetic homogeneity.
      Further research is needed to evaluate all of the polymorphic markers in the COMT
      gene and its nearby regulatory elements for association with schizophrenia.
      Identification of specific COMT-dependent molecular, cellular and circuit
      deficits will provide targets for the development of more efficient treatments
      for the cognitive and psychiatric symptoms in 22q11DS.

PMID- 22483290
TI  - Inhibitors of Catechol-O-Methyltransferase.
AB  - Since the identification of Catechol-O-Methyltransferase (COMT) by Axelrod in
      1957, many inhibitors of this enzyme have been reported. While COMT inhibition
      may be beneficial in a number of disease states, most of the effort over the
      years has been directed at boosting L-DOPA concentrations as adjunct treatment
      for Parkinson's disease. This review summarizes the major classes of COMT
      inhibitors, from early catechol and pyrogallol variants to bisubstrate
      inhibitors. The nitrocatechol substructure has proven to be a particularly
      productive scaffold, resulting in two marketed drugs and several improved drug
      candidates working their way through clinical trials.

PMID- 22483291
TI  - Role of catechol-O-methyltransferase (COMT)-dependent processes in Parkinson's
      disease and L-DOPA treatment.
AB  - One of the most important enzymes in the catecholamine cycle, catecholamine-O
      methyltransferase (COMT), plays a critical role in the extracellular metabolism
      of dopamine and norepinephrine both in the periphery and the central nervous
      system. COMT has attracted strong interest in regards to its role in dopamine
      related pathologies, particularly Parkinson's disease. There are several
      mechanisms for the potential involvement of COMT-related processes in the
      pathophysiology of Parkinson's disease or the consequences of L-DOPA treatment.
      COMT-mediated metabolism of LDOPA in the periphery influences brain dopamine
      levels, while the product of central COMT-mediated dopamine metabolism, 3
      methoxytyramine, can affect movement via interaction with Trace Amine-Associated
      Receptor 1 (TAAR1). COMT inhibitors have a long history of clinical use in the
      treatment of Parkinson's disease. Several clinical genetic studies have shown
      that variants of COMT gene contribute to the manifestations or treatment
      responses of this disorder. Here, we review the basic molecular mechanisms that
      could be involved in COMT-dependent processes in Parkinson's disease, the
      pharmacological properties of COMT inhibitors used in the treatment of this
      disorder and the clinical genetic observations involving COMT gene variants as
      modulators of pathological processes and responses to dopamine replacement
      therapies used in the treatment of the disorder.

PMID- 22483292
TI  - Catechol-O-methyltransferase (COMT) pharmacogenetics in the treatment response
      phenotypes of major depressive disorder (MDD).
AB  - Psychiatry is a specialty where the application of pharmacogenomics approaches is
      made to the study of interindividual differences in response to antidepressants.
      It is highly applied for improving patient treatment. Major depressive disorder
      (MDD) is a common and complex disorder resulting from genetic and environmental
      interactions. Less than 40% of patients with MDD achieve remission, and even
      after several treatment trials, one in three patients do not fully recover from
      MDD. Many clinical and genomic association studies suggested that the catechol-O
      methyltransferase (COMT) gene region was an important genetic locus for
      psychiatric disorders, because of the proposed relationship between its function
      in catecholaminergic neurotransmission and individual response to
      antidepressants, and vulnerability to psychiatric disorders. Although a number of
      COMT single nucleotide polymorphisms (SNPs) were observed, the Val108/158Met
      (rs4680) polymorphism in exon 4 resulted in a change in the enzyme structure
      which has been intensively investigated in relation to its role of enzyme
      activity and processes of prefrontal cortex functions in cognition. As serotonin
      interacts with dopamine and dopamine availability is influenced by COMT SNPs, an
      association between the COMT gene and response to treatment, based on the various
      pharmacogenetics/pharmacogenomics studies about COMT gene published to date, is
      explored in this overview.

PMID- 22483294
TI  - Catechol-o-methyltransferase and Alzheimer's disease: a review of biological and
      genetic findings.
AB  - Alzheimer's disease (AD) is the leading cause of dementia worldwide and is
      associated with a marked individual, familial and social burden. Catechol-O
      mehyltransferase (COMT) is surfacing with a prominent role in AD pathophysiology
      by affecting the metabolism of catecholamine neurotransmitters and estrogen. COMT
      gene regulates dopamine levels in the prefrontal cortex which are involved in
      working memory and executive functioning. Impaired executive functioning is
      reported in a subgroup of AD patients and is associated with a more severe
      disorder, a more rapid disease progression and a shorter survival. The COMT
      rs4680 gene polymorphism has been investigated as a susceptibility factor for AD.
      No statistically significant results were found in meta-analysis but one study
      reported that the rs4680 Val allele was associated with AD-related psychosis. The
      COMT rs4680 polymorphism was also found to modulate declarative episodic memory
      in normal people and schizophrenic subjects. COMT inhibitors, that are adjunctive
      drugs in Parkinson's disease treatment, lower homocysteine levels and improve
      executive memory processes in normal subjects. A preliminary study, which needs
      replication, demonstrates that COMT inhibitors block beta-amyloid fibrils in
      vitro. Taken together, these findings suggest that research should focus on the
      role of COMT in AD pathogenesis and on the feasibility of targeting COMT activity
      in AD treatment.

PMID- 22483295
TI  - Catechol-o-methyl transferase modulates cognition in late life: evidence and
      implications for cognitive enhancement.
AB  - Aging is associated with deficits in several cognitive domains as well as a
      decline in brain dopamine activity. Catechol-O-methyl transferase (COMT), an
      enzyme involved in the degradation of dopamine, is a critical determinant of the
      availability of this neurotransmitter in the prefrontal cortex. A functional
      single nucleotide polymorphism in the COMT gene, Val158Met, modulates the
      activity of this enzyme and affects cognition and the brain regions underlying
      this function. The effects of COMT Val158Met polymorphism are magnified in the
      aging brain. Here, we review the evidence supporting a role of COMT genetic
      variation in cognitive as well as structural and functional brain changes
      associated with senescence. We will address the potential modulatory role of
      genetic and non-genetic factors on the neural and cognitive effects of COMT
      Val158Met in late life. Furthermore, we will discuss the viability of a COMT
      targeted treatment for improving cognitive efficiency in aging.

PMID- 22483293
TI  - The role of the catechol-O-methyltransferase (COMT) gene in personality and
      related psychopathological disorders.
AB  - This review provides a short overview of the most significant biologically
      oriented theories of human personality. Personality concepts of Eysenck, Gray and
      McNaughton, Cloninger and Panksepp will be introduced and the focal evidence for
      the heritability of personality will be summarized. In this context, a synopsis
      of a large number of COMT genetic association studies (with a focus on the COMT
      Val158Met polymorphism) in the framework of the introduced biologically oriented
      personality theories will be given. In line with the theory of a continuum model
      between healthy anxious behavior and related psychopathological behavior, the
      role of the COMT gene in anxiety disorders will be discussed. A final outlook
      considers new research strategies such as genetic imaging and epigenetics for a
      better understanding of human personality.

PMID- 22483296
TI  - COMT as a drug target for cognitive functions and dysfunctions.
AB  - Catechol-O-methyltransferase (COMT) is a promising target for modulation of
      cognitive functions and dysfunctions. COMT dominates the regulation of dopamine
      metabolism in the prefrontal cortex. Thus, COMT effects are particularly evident
      in prefrontal cortex-dependent cognitive functions including executive control,
      working memory, attentional control and long-term memory. This has been
      determined by both genetic and pharmacological studies that we will highlight in
      the present review. In particular, we will discuss how common functional variants
      of the COMT gene may predict individual variation in selective cognitive
      abilities and vulnerability to cognitive deficits that characterize several
      neuropsychiatric disorders. Moreover, COMT genetic variants represent one source
      of individual differences in the cognitive responses to medications such as those
      used in psychiatric illnesses. COMT genetic testing may then predict some
      cognitive dysfunctions often seen in certain psychiatric illnesses even from
      presymptomatic stages and the efficacy/dosage of drugs used to treat them. The
      consideration of COMT-dependent differences may be important for the development
      of more efficient personalized healthcare.

PMID- 22483298
TI  - Catechol-O-methyl transferase as a drug target for schizophrenia.
AB  - Current antipsychotic drugs lack material efficacy against the negative symptoms
      and cognitive deficits of schizophrenia. There is considerable uncertainty
      regarding the optimal pharmacotherapeutic strategy for treating these and other
      aspects of psychotic illness. The present review summarises clinical, mutant, and
      psychopharmacological data related to catechol-O-methyltransferase (COMT), an
      enzyme involved in the catabolism of catecholamine neurotransmitters, with a view
      to establishing the antipsychotic potential of compounds targeting the action of
      this enzyme. The review examines clinical and preclinical genetic data linking
      COMT gene variation with risk for schizophrenia or specific symptoms or disease
      endophenotypes. We then summarise data concerning the behavioural effects of COMT
      inhibitors. These genetic and pharmacological data relating to COMT as a
      therapeutic target have implications for the development of individualised
      treatments for treatment-resistant symptoms of schizophrenia, including cognitive
      dysfunction and, potentially, negative symptoms.

PMID- 22483297
TI  - Janus molecule I: dichotomous effects of COMT in neuropathic vs nociceptive pain
      modalities.
AB  - The enzyme catechol-O-methyltransferase (COMT) has been shown to play a critical
      role in pain perception by regulating levels of epinephrine (Epi) and
      norepinephrine (NE). Although the key contribution of catecholamines to the
      perception of pain has been recognized for a long time, there is a clear
      dichotomy of observations. More than a century of research has demonstrated that
      increasing adrenergic transmission in the spinal cord decreases pain sensitivity
      in animals. Equally abundant evidence demonstrates the opposite effect of
      adrenergic signaling in the peripheral nervous system, where adrenergic signaling
      increases pain sensitivity. Viewing pain processing within spinal and peripheral
      compartments and determining the directionality of adrenergic signaling helps
      clarify the seemingly contradictory findings of the pain modulatory properties of
      adrenergic receptor agonists and antagonists presented in other reviews.
      Available evidence suggests that adrenergic signaling contributes to pain
      phenotypes through alpha(1/2) and beta(2/3) receptors. While stimulation of
      alpha(2) adrenergic receptors seems to uniformly produce analgesia, stimulation
      of alpha(1) or beta receptors produces either analgesic or hyperalgesic effects.
      Establishing the directionality of adrenergic receptor modulation of pain
      processing, and related COMT activity in different pain models are needed to
      bring meaning to recent human molecular genetic findings. This will enable the
      translation of current findings into meaningful clinical applications such as
      diagnostic markers and novel therapeutic targets for complex human pain
      conditions.

PMID- 22483299
TI  - Current understanding of the interplay between catechol-O-methyltransferase
      genetic variants, sleep, brain development and cognitive performance in
      schizophrenia.
AB  - Abnormal sleep is an endophenotype of schizophrenia. Here we provide an overview
      of the genetic mechanisms that link specific sleep physiological processes to
      schizophrenia-related cognitive defects. In particular, we will review the
      possible relationships between catechol-O-methyltransferase (COMT), sleep
      regulation and schizophrenia development. Recent studies validate the hypothesis
      that COMT mutations may trigger disturbances during adolescence that affect sleep
      and cortical development. Anomalies in cortical development during this critical
      developmental phase may increase the susceptibility for schizophrenia. In
      conclusion, in view of therapeutic efficacy, we can envisage indications for
      future investigations into the role of COMT for sleep regulation, cognitive
      performance and sleep-related cognitive deficits.

PMID- 22483300
TI  - The role of catechol-O-methyltransferase in reward processing and addiction.
AB  - Catechol-O-methyltransferase (COMT) catabolises dopamine and is important for
      regulating dopamine levels in the prefrontal cortex. Consistent with its
      regulation of prefrontal cortex dopamine, COMT modulates working memory and
      executive function; however, its significance for other cognitive domains, and in
      other brain regions, remains relatively unexplored. One such example is reward
      processing, for which dopamine is a critical mediator, and in which the striatum
      and corticostriatal circuitry are implicated. Here, we discuss emerging data
      which links COMT to reward processing, review what is known of the underlying
      neural substrates, and consider whether COMT is a good therapeutic target for
      treating addiction. Although a limited number of studies have investigated COMT
      and reward processing, common findings are beginning to emerge. COMT appears to
      modulate cortical and striatal activation during both reward anticipation and
      delivery, and to impact on reward-related learning and its underlying neural
      circuitry. COMT has been studied as a candidate gene for numerous reward-related
      phenotypes and there is some preliminary evidence linking it with certain aspects
      of addiction. However, additional studies are required before these associations
      can be considered robust. It is premature to consider COMT a good therapeutic
      target for addiction, but this hypothesis should be revisited as further
      information emerges. In particular, it will be critical to reveal the precise
      neurobiological mechanisms underlying links between COMT and reward processing,
      and the extent to which these relate to the putative associations with addiction.

PMID- 22483301
TI  - Commentary: Keeping the batteries charged in Parkinson's disease.

PMID- 22483302
TI  - Conference report: 1st workshop on "palmitoylethanolamide: biochemistry,
      pharmacology and therapeutic use of a pleiotropic anti-inflammatory lipid
      mediator".

PMID- 22483303
TI  - Mn (III) tetrakis (4-benzoic acid) porphyrin protects against neuronal and glial
      oxidative stress and death after spinal cord injury.
AB  - This study explores the ability of a catalytic antioxidant, Mn (III) tetrakis (4
      benzoic acid) porphyrin (MnTBAP), to protect against neuronal and glial oxidative
      stress and death after spinal cord injury (SCI). Nine different doses of MnTBAP
      were administered into the intrathecal space of the rat spinal cord immediately
      following moderate SCI to establish dose - response curves for prevention of
      lipid peroxidation and neuron death. An optimal dose was determined by comparing
      the effectiveness of MnTBAP protection among doses. The optimal dose was then
      administered and the cords were removed 24 h post-administration and processed
      for staining. The cells in the cord sections at different distances from the
      epicenter were counted to obtain the spatial profiles of MnTBAP protection.
      Comparison of the counts between MnTBAP- and vehicle-treated groups in the
      sections double immuno-fluorescence-stained with oxidative and cellular markers
      demonstrated that MnTBAP significantly reduced numbers of nitrotyrosine- and DNP
      positive (stained with an antibody against 2,4-dinitrophenyl hydrazine (DNPH)
      labeled protein carbonyls) neurons, astrocytes, and oligodendrocytes. Comparison
      of the counts between the two treatments in the sections immuno-stained with
      cellular markers revealed that MnTBAP significantly increased numbers of neurons,
      motoneurons, astrocytes, and oligodendrocytes. MnTBAP more effectively reduced
      neuronal than glial cell death. Post-injury treatment with the optimal dose of
      MnTBAP at 6, 12, 24, 48, and 72 h post-SCI demonstrated that the effective time
      window for reducing protein nitration and neuron death was at least 12 h. Our
      results demonstrated that MnTBAP combats oxidative stress, thereby attenuating
      all types of cell death after SCI.

PMID- 22483304
TI  - Anti-parkinsonian effects of Nurr1 activator in ubiquitin-proteasome system
      impairment induced animal model of Parkinson's disease.
AB  - Nurr1 is a member of the nuclear receptor superfamily and is a potential
      susceptibility gene for Parkinson's disease (PD). Several lines of studies in
      vitro and in vivo reported that defects in the Nurr1 gene cause nigrostriatal
      neuronal deficiency as seen in PD. In the present study, we used a a synthetic
      low molecular weight Nurr1 activator which increases the transcription of Nurr1
      to investigate whether it has anti-parkinsonian effects against nigrostriatal
      neuronal degeneration induced by proteasome inhibitor lactacystin. Adult C57BL/6
      mice were treated orally with the Nurr1 activator and an inactive structural
      analog as a control at a dose of 10mg/kg per day, starting 3 days before
      microinjection of proteasome inhibitor lactacystin into the medial forebrain
      bundle and the treatment continued for a total of 4 weeks. Animal behavior tests,
      and pathological and biochemical examinations were performed to determine the
      anti-parkinsonian effects of the Nurr1 activator. We found that treatment with
      the Nurr1 activator significantly improved rotarod performance, attenuated
      dopamine neuron loss and nigrostriatal dopamine reduction, increased expression
      of Nurr1, dopamine transporter and vesicular monoamine transporter 2, and
      alleviated microglial activation in the substantia nigra of lactacystin-lesioned
      mice. These results suggest that the Nurr1 activator may become an innovative
      strategy for the treatment of PD.

PMID- 22483305
TI  - Methylene blue inhibits the function of alpha7-nicotinic acetylcholine receptors.
AB  - Methylene Blue (MB) is being investigated in clinical studies for its beneficial
      effects in the treatment of Alzheimer disease. However, its exact mechanisms of
      action have not been fully elucidated. The modulation of nicotinic acetylcholine
      receptors (nAChRs) has been suggested to play a role in the pathogenesis of
      various neurodegenerative diseases. Therefore, in the present study, the effect
      of MB on the function of the cloned alpha7 subunit of the human nAChR expressed
      in Xenopus oocytes was investigated using the two-electrode voltage-clamp
      technique. MB reversibly inhibited ACh (100 MUM)-induced currents in a
      concentration-dependent manner with an IC50 value of 3.4+/-0.3 MUM. The effect of
      MB was not dependent on the membrane potential. MB did not affect the activity of
      endogenous Ca2+-dependent Cl- channels, since the inhibition by MB was unaltered
      in oocytes injected with the Ca2+ chelator 1,2-bis (o-aminophenoxy) ethane-N, N,
      N', N'-tetraacetic acid and perfused with Ca2+-free bathing solution containing
      1.8 mM Ba2+. MB decreased the maximal ACh-induced responses without significantly
      affecting ACh potency. Furthermore, specific binding of [125I] alpha
      bungarotoxin, a radioligand selective for the alpha7 nAChR, was not altered by MB
      (10 MUM), indicating that MB acts as a noncompetitive antagonist on alpha7
      nAChRs. In hippocampal slices, whole-cell recordings from CA1 pyramidal neurons
      indicated that the increases in the frequency and amplitudes of the gamma
      aminobutyric acid-mediated spontaneous postsynaptic currents induced by bath
      application of 2 mM choline, a specific agonist for alpha7 nAChRs, were abolished
      after 10 min application of 3 MUM MB. These results demonstrate that MB inhibits
      the function of human alpha7 nAChRs expressed in Xenopus oocytes and of alpha7
      nAChR-mediated responses in rat hippocampal neurons.

PMID- 22483306
TI  - Redox sensitivity of tyrosine hydroxylase activity and expression in dopaminergic
      dysfunction.
AB  - Oxidant molecules generated during neuronal metabolism appear to play a
      significant role in the processes of aging and neurodegeneration. Increasing
      experimental evidence suggests the noteworthy relevance of the intracellular
      reduction-oxidation (redox) balance for the dopaminergic (DA-ergic) neurons of
      the substantia nigra pars compacta. These cells possess a distinct physiology
      intrinsically associated with elevated reactive oxygen species production,
      conferring on them a high vulnerability to free radical damage, one of the major
      causes of selective DA-ergic neuron dysfunction and degeneration related to
      neurological disorders such as Parkinson's disease. Tyrosine hydroxylase
      (tyrosine 3-monooxygenase; E.C. 1.14.16.2; TH) activity represents the rate
      limiting biochemical event in DA synthesis. TH activity, metabolism and
      expression are finely tuned by several regulatory systems in order to maintain a
      crucial physiological condition in which DA synthesis is closely coupled to its
      secretion. Alterations of these regulatory systems of TH functions have indeed
      been thought to be key events in the DA-ergic degeneration. TH has seven cysteine
      residues presenting thiols. Depending on the oxido-reductive (redox) status of
      the cellular environment, thiols exist either in the reduced form of free thiols
      or oxidized to disulfides. The formation of disulfides in proteins exerts
      critical regulatory functions both in physiological and in pathological
      conditions when oxidative stress is sustained. Several reports have recently
      shown that redox state changes of thiol residues, as consequence of an oxidative
      injury, can directly or indirectly affect the TH activity, metabolism and
      expression. The major focus of this review, therefore, is to report recent
      evidence on the redox modulation of TH activity and expression, and to provide an
      overview of a cellular phenomenon that might represent a target for new
      therapeutic strategies against the DA-ergic neurodegenerative disorders.

PMID- 22483307
TI  - RNAi of cat-2, a putative tyrosine hydroxylase, increases alpha synuclein
      aggregation and associated effects in transgenic C. elegans.
AB  - Neurodegenerative Parkinson's disease (PD) is a multifactorial disorder; effects
      like alpha synuclein aggregation, low dopamine levels and dopaminergic
      neurodegeneration are considered to be hallmarks of the disease. Several recent
      studies have pointed towards an important role of enzyme tyrosine hydroxylase
      (TH) in the pathophysiology of PD. We embarked on the present studies to explore
      the mechanistic role of C. elegans gene cat-2, a putative tyrosine hydroxylase,
      in PD. Utilizing the powerful genetic model system C. elegans, which has
      previously provided critical understanding of several human diseases, we employed
      a reverse genetics approach via RNAi mediated gene silencing of cat-2, to study
      various disease related effects in three different transgenic strains of the
      nematode. Knocking-down of cat-2 led to increase in aggregation of alpha
      synuclein, as was studied via expression of YFP. Similarly the silencing of cat-2
      had significant effects on associated endpoints including oxidative stress, lipid
      content and neurotransmission; exemplifying the role of cat-2, the putative
      tyrosine hydroxylase, in Parkinsonism of the nematode model. The findings are
      significant as this model could further be used to study the entire associated
      pathway in greater detail and with the advantages that the model system C.
      elegans presents, the knockdown of cat-2 in the alpha synuclein expressing
      strain, could be employed for screening potential pharmacological agents targeted
      at TH which could lead to designing of possible therapeutic interventions for the
      disease.

PMID- 22483308
TI  - Paradoxical sleep deprivation modulates tyrosine hydroxylase expression in the
      nigrostriatal pathway and attenuates motor deficits induced by dopaminergic
      depletion.
AB  - The nigrostriatal pathway is very likely involved in sleep regulation,
      considering the occurrence and high prevalence of sleep-related disorders in
      patients with Parkinson's disease. Indeed, dopaminergic neurons in the ventral
      tegmental area were recently shown to fire in bursts during paradoxical sleep
      (PS), but little is known about the activity of the nigrostriatal dopamine (DA)
      cells in relation to PS. In view of that we hypothesized that paradoxical sleep
      deprivation (PSD) may play a relevant role in nigrostriatal tyrosine hydroxylase
      (TH) expression and, subsequently, in sleep rebound. The present study was
      designed to determine the effects of PSD in the nigrostriatal pathway in mice by
      means of neurochemical and behavioral approaches. Intraperitoneal reserpine (1
      mg/kg) associated to alpha-methyl-p-tyrosine (alphaMT) (250 mg/kg) to produce
      catecholamine depletion, or rotenone (10 mg/kg) to increase striatal DA turnover
      were injected 30 min before the 24 h of PSD. Catalepsy and open-field tests
      indicated that motor deficits induced by reserpine-alphaMT were counteracted by
      PSD, which, in contrast, potentiated the motor impairment induced by rotenone.
      Besides, PSD produced down-regulation on TH expression within the substantia
      nigra pars compacta and striatum, without affecting the number or the optical
      density of dopaminergic neurons present in the respective areas. Interestingly,
      PSD potentiated the downregulation of TH expression in the substantia nigra pars
      compacta and striatum induced by the co-administration of reserpine-alphaMT.
      These results reinforce the notion of a strong participation of DA in PS, as a
      consequence of the modulation of TH protein expression in the nigrostriatal
      pathway.

PMID- 22483309
TI  - Motor and non-motor features of Parkinson's disease - a review of clinical and
      experimental studies.
AB  - Classically, Parkinson's disease (PD) is considered to be a motor system
      affliction and its diagnosis is based on the presence of a set of cardinal motor
      signs (e.g. rigidity, bradykinesia, rest tremor and postural reflex disturbance).
      However, there is considerable evidence showing that non-motor alterations (e.g.
      anxiety, depression, sleep, gastrointestinal and cognitive functions) precede the
      classical motor symptoms seen in PD. The management of these nonmotor symptoms
      remains a challenge. A pattern of regional neurodegeneration that varies
      considerably depending upon the neuronal population affected may explain the
      different symptoms. In fact, differential mechanisms of neuronal vulnerability
      within the substantia nigra pars compacta (SNpc) suggests that factors other than
      location contribute to the susceptibility of these neurons. In this review we
      discuss how these factors interact to ultimately target the SNpc. Remarkably,
      this region consists of approximately 95% of the tyrosine hydroxylase (TH)
      immunoreactive neurons in both human and rat brains, and consequently this
      implicates elevated levels of dopamine metabolites, free radicals and other
      hazard species in these neurons. An understanding of how these factors promote
      neuronal death may be useful for the development of novel neuroprotective and/or
      neurorestorative strategies for PD.

PMID- 22483310
TI  - Mitochondria as an easy target to oxidative stress events in Parkinson's disease.
AB  - Parkinson's disease (PD) is related to excess production of reactive oxygen
      species (ROS) or inadequate and impaired detoxification by endogenous
      antioxidants, alterations in catecholamine metabolism, alterations in
      mitochondrial electron transfer function, and enhanced iron deposition in the
      substantia nigra. The concept that oxidative stress is an important mechanism
      underlying the degeneration of dopaminergic (DAergic) neurons is reinforced by
      data documenting that high levels of lipid peroxidation, increased oxidation of
      proteins and DNA and depletion of glutathione are observed in postmortem studies
      of brain tissues of PD patients. Tyrosine hydroxylase (TH) is an important
      neuronal enzyme that, in the presence of tetrahydrobiopterin, catalyzes the
      initial and rate-limiting step in the biosynthesis of the catecholamine
      neurotransmitters dopamine (DA) and norepinephrine, and is frequently used as a
      marker of DAergic neuronal loss in animal models of PD. The role for TH as
      generators of ROS are highly relevant to PD because ROS have been proposed to
      contribute to the neurodegeneration of DA neurons. Oxidants and superoxide
      radicals are produced as byproducts of oxidative phosphorylation, making
      mitochondria the main site of ROS generation within the cell and the site of the
      first line of defence against oxidative stress. ROS can affect mitochondrial DNA
      (mtDNA) causing modulation in synthesis of electron transport chain (ETC)
      components, decreased ATP production, and increased leakage of ROS.

PMID- 22483311
TI  - New agents promote neuroprotection in Parkinson's disease models.
AB  - Although researchers are pursuing "disease modifying" medications to slow or stop
      Parkinson's disease (PD) progression, a myriad of agents with protective
      properties in cell cultures and animal models have yielded few treatments in
      clinical practice. Developing safe and effective treatments with disease
      modifying/neuroprotective mechanisms of action and identifying patients in the
      pre-motor phase will be a challenge. The implication of tyrosine hydroxylase
      (TH), the enzyme that catalyzes the formation of L-3,4-dihydroxyphenylalanine, in
      the pathogenesis of PD at different levels makes it a promising candidate for
      developing efficient treatment based on correcting or bypassing the enzyme
      deficiency. TH is also the key enzyme for immunorreactivity in PD models and is
      used to assess the efficacy of novel disease-modifying medications. PD animal
      models are genetic: alpha-synuclein models, parkin (PINK 1 and DJ1) and leucine
      rich repeat kinase 2 or pharmacological and neurotoxic: reserpine, 6
      hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine, rotenone,
      paraquat/maneb, and trichloroethylene. This review is focused on the state of art
      of PD models, the relationship with TH, and potential neuroprotective agents to
      treat PD. The latter include gene therapy, transplantation, erythropoietin,
      natural phenolic compounds, doxycycline, ethyl pyruvate, 9-methyl-beta-carboline,
      vascular endothelial growth factor, simvastatin, zonisamide, modafinil,
      melatonin, cannabinoids, rottlerin, fluoxetine, paroxetine, coenzyme Q10, N
      acetylcysteine and vaccines like Bacille Calmette-Guerin, with different proposed
      mechanisms of action. Also of note is the link between hypovitaminosis D and
      neurodegeneration opening new perspectives in research with TH genes and PD
      models treated with vitamin D. Translational scientists can contribute to a
      better understanding of the pathogenesis of PD and lead to more effective
      treatments.

PMID- 22483312
TI  - Targeting Parkinson's - tyrosine hydroxylase and oxidative stress as points of
      interventions.
AB  - Parkinson's disease (PD) is characterized by the progressive loss of the
      dopaminergic neurons leading to decrease in striatal dopamine (DA) levels. In the
      present review, our focus was on recent advances in the treatment procedures of
      PD to achieve an increase in deficient tyrosine hydroxylase (TH) activity and/or
      expression. Stimulation of residual TH activity by the cofactors, 6R-L-erythro
      tetrahydrobiopterin (BPH4) or NADH, or by brain transplant of natural TH
      containing cells (fetal substantia nigra) or genetically engineered TH-containing
      cells, has been tried experimentally and clinically lately. As a promising
      approach to the gene therapy, intrastriatal expression of DAsynthesizing enzymes
      through transduction with separate adeno-associated virus (AAV) vectors/ marrow
      stromal cells (MSCs) or nonviral intravenous administration of rat transferrin
      receptor monoclonal antibody (TfRmAb)-targeted PEGylated immunoliposomes (PILs)
      has been found to be effective in animal models. Oxidative stress has been
      identified as one of the intermediary risk factors that could initiate and/or
      promote degeneration of DA neurons. TH itself is a prime target of
      oxidative/nitrosative injury. Certain superoxide dismutase and catalase mimetic
      prevented nitration of TH in cultured dopaminergic neurons. Therefore,
      development of therapeutic agents that can prevent formation of or specifically
      remove nitrating agents without interfering with normal neuronal function may
      protect protein from inactivation and provide means of limiting neuronal injury
      in PD. Non-pharmacological approaches such as diet therapy or use of active
      constituents of plants and phytomedicines have also emerged as a new - area of
      high interest. New treatment strategies for TH dysfunction rectification, a
      provision for neuroprotection in PD, seem to be on the horizon with many
      therapies under investigation.

PMID- 22483314
TI  - The function of tyrosine hydroxylase in the normal and Parkinsonian brain.
AB  - Tyrosine hydroxylase (TH) is the rate limiting step in the biosynthesis of
      dopamine and other catecholamines. Differences have been noted in concentration
      and availability of this enzyme and its cofactors in disease states such as
      Parkinson's disease (PD) which are subject to alterations in catecholamines. More
      evidence suggests in fact that TH may play a direct role in the pathogenesis of
      PD, especially through oxidative stress and pro-inflammatory mechanisms.
      Treatment for PD has classically involved maximizing endogenous dopamine by
      medicinal options that either replace dopamine or augment the dopaminergic
      pathway. The medications are unfortunately limited, given they are not curative
      and involve potential short-term and long-term side effects. Gene therapy in PD
      is a burgeoning field which provides a way to augment dopamine production, and
      potentially protect the dopaminergic neurons from further degeneration. Given its
      importance in dopamine catabolism and the possibility that it may contribute to
      pathogenesis, TH is one target of gene therapy. Further research into the
      regulatory mechanisms and function of TH are promising in improving gene therapy
      approaches as well as other treatment modalities.

PMID- 22483315
TI  - Moving beyond tyrosine hydroxylase to define dopaminergic neurons for use in cell
      replacement therapies for Parkinson's disease.
AB  - Cell replacement therapies are an attractive mode of treatment for
      neurodegenerative disorders as they have the potential to alleviate or modify
      disease symptoms and restore function. In Parkinson's disease, the cell type
      requiring replacement is dopamine-producing neurons of the midbrain. The source
      of replacement cells is contentious, with opinion still evolving. Clinical trials
      have previously used fetal brain tissue; however, this will likely be superseded
      by the use of embryonic or induced pluripotent stem cells, due to their greater
      availability and homogeneity. One significant caveat in the use of any cell
      source for therapy is that cells must first be adequately characterised and
      purified. The gold standard marker in the identification of dopaminergic neurons
      is tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis,
      catalyzing the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine. However,
      there are multiple ways of measuring TH readout, and potential flaws in the
      fidelity of TH expression. This review will look at the complex regulatory
      mechanisms that govern different facets of TH expression, including reported
      differences in TH expression in vitro and in vivo. We will also examine the
      regulation of the TH gene; assessing the which, the where and the when of TH
      expression. We will look at how knowledge of regulation of the TH gene can be
      utilised to enhance research efforts. And, finally we will delve into the
      transcription factors that govern elements of TH expression, and which may prove
      more effective for defining appropriate dopaminergic neuron precursor cells.

PMID- 22483316
TI  - Overview of tyrosine hydroxylase in Parkinson's disease.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in brain catecholamine
      biosynthesis, and tetrahydrobiopterin is its cofactor. Research has focused on
      identifying mechanisms of TH activity regulation. TH activity is modulated by the
      cofactor itself, and is enhanced by several kinases phosphorylating key serines
      in the TH regulatory domain. Aside from these, the mechanisms that control TH
      gene transcription and TH mRNA translation are also related with the regulation
      of TH activity. Parkinson's disease (PD) is characterized by severe loss of
      dopaminergic neurons and depletion of dopamine in substantia nigra. Reduction of
      TH expression results in diminished dopamine synthesis and leads to PD; thus TH
      is essential in the pathogenesy of PD. It has also been shown that dysregulation
      of TH activity will contribute to PD. For example, alpha-synuclein represses TH
      not only by inhibiting phosphorylation at Ser40 of TH, but also by stimulating
      protein phosphatase 2A activity, which decreases dopamine synthesis and leads to
      parkinsonism. Based on these studies of TH in PD pathogenesis, a therapeutic
      strategy aimed to improve striatal TH expression in PD has received wide
      interest. Evidence shows that using drugs or other treatment methods such as gene
      replacement therapy to increase nigrostriatal TH expression is an effective
      therapy for PD. Further investigation of TH regulatory mechanisms will not only
      provide additional drug targets for PD, but may also help to identify new PD
      therapeutics.

PMID- 22483313
TI  - A synopsis on the role of tyrosine hydroxylase in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common chronic progressive neurodegenerative
      disorder in elderly people. A consistent neurochemical abnormality in PD is
      degeneration of dopaminergic neurons in substantia nigra pars compacta, leading
      to a reduction of striatal dopamine (DA) levels. As tyrosine hydroxylase (TH)
      catalyses the formation of L-dihydroxyphenylalanine (L-DOPA), the rate-limiting
      step in the biosynthesis of DA, the disease can be considered as a TH-deficiency
      syndrome of the striatum. Problems related to PD usually build up when vesicular
      storage of DA is altered by the presence of either alpha-synuclein protofibrils
      or oxidative stress. Phosphorylation of three physiologically-regulated specific
      sites of N-terminal domain of TH is vital in regulating its kinetic and protein
      interaction. The concept of physiological significance of TH isoforms is another
      interesting aspect to be explored further for a comprehensive understanding of
      its role in PD. Thus, a logical and efficient strategy for PD treatment is based
      on correcting or bypassing the enzyme deficiency by the treatment with L-DOPA, DA
      agonists, inhibitors of DA metabolism or brain grafts with cells expressing a
      high level of TH. Neurotrophic factors are also attracting the attention of
      neuroscientists because they provide the essential neuroprotective and
      neurorestorative properties to the nigrostriatal DA system. PPAR-gamma, a key
      regulator of immune responses, is likewise a promising target for the treatment
      of PD, which can be achieved by the use of agonists with the potential to impact
      the expression of pro- and anti-inflammatory cytokines at the transcriptional
      level in immune cells via expression of TH. Herein, we review the primary
      biochemical and pathological features of PD, and describe both classical and
      developing approaches aimed to ameliorate disease symptoms and its progression.

PMID- 22483318
TI  - Non-typhi Salmonella serovars found in Mexican zoo animals.
AB  - The aim of the present study was to determine the bacteriological prevalence of
      subclinical non-typhi Salmonella infections in zoo animals and to determine the
      most frequently isolated serovars of the bacteria. A total of 267 samples were
      analyzed, including fecal samples from zoo animals and rodents, insects (Musca
      domestica and Periplaneta americana) and samples of the zoo animal's food.
      Salmonella was detected in 11.6% of the samples analyzed. Characterization of the
      isolates was performed with serotyping and pulsed-field gel electrophoresis. The
      following serovars were isolated: S. San Diego, S. Oranienburg, S. Weltevreden,
      S. Braenderup, S. Derby, S. 6,7, H:en x:- and S. 3,10, H:r:-. The isolates showed
      seven pulsed-field gel electrophoresis patterns with a Jaccard coefficient>=0.75
      indicating a possible common origin. The prevalence of asymptomatic infections
      caused by Salmonella spp. in zoo animals was high. These findings demonstrate the
      diversity of Salmonella serovars in several captive wild animal species.

PMID- 22483319
TI  - Necrotizing enterocolitis in HIV-exposed and nonexposed infants: clinical
      presentation and histopathological features.
AB  - Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in
      neonates and is associated with significant morbidity and mortality. An
      association between HIV-positive maternal status and increased risk of NEC in
      preterm infants has been described, and antiretroviral therapy has been proposed
      as an independent risk factor. Our aim was to compare the clinical presentation
      and histopathological features of necrotizing enterocolitis in HIV-exposed and
      unexposed infants. A retrospective study of archival material from the National
      Health Laboratory Services Histopathology Laboratory in Tygerberg
      Hospital/Stellenbosch University from 1992 to 2008 was conducted. All surgical
      specimens from infants who presented to pediatric surgery for a laparotomy and
      bowel resection for NEC and in whom the HIV status was known were included in the
      study. In the 37 cases that fulfilled these criteria, male gender was
      overrepresented in the study population (67%). Nonsteroidal anti-inflammatory
      drugs appeared to play a significant role in the development of surgical NEC in
      infants who were not exposed to HIV, but HIV-exposed infants had a significantly
      poorer survival rate. There was no significant difference in the histopathology
      between HIV-exposed and nonexposed infants, and Cytomegalovirus infection was not
      identified in any of the cases studied.

PMID- 22483320
TI  - Vascular malformations in childhood.
AB  - Vascular malformations are inborn errors of vascular embryogenesis present at
      birth that should be diagnosed in childhood and, when necessary, treated to
      prevent later complications. The current trend is to classify these lesions
      according to flow characteristics and the predominant type of vascular channel
      affected. Given the complexity, and in many cases, the rarity, of vascular
      malformations, they should be managed by multidisciplinary teams at vascular
      anomalies centers. Furthermore, because the association between vascular
      malformations and certain syndromes is becoming increasingly recognized, a better
      understanding of these lesions will help to improve overall patient management in
      this setting.

PMID- 22483321
TI  - Zosteriform connective tissue nevus: a new case report.

PMID- 22483322
TI  - Cutaneous CD8+ T-cell infiltrates associated with human immunodeficiency virus.

PMID- 22483323
TI  - Mastectomy trends for early-stage breast cancer: a report from the EUSOMA multi
      institutional European database.
AB  - INTRODUCTION: Recent single-institution reports have shown increased mastectomy
      rates during the last decade. Further studies aiming to determine if these
      reports could be reflecting a national trend in the United States of America (US)
      have shown conflicting results. We report these trends from a multi-institutional
      European database. PATIENTS AND METHODS: Our source of data was the eusomaDB, a
      central data warehouse of prospectively collected information of the European
      Society of Breast Cancer Specialists (EUSOMA). We identified patients with newly
      diagnosed unilateral early-stage breast cancer (stages 0, I or II) to examine
      rates and trends in surgical treatment. RESULTS: A total of 15,369 early-stage
      breast cancer cases underwent surgery in 13 Breast Units from 2003 to 2010.
      Breast conservation was successful in 11,263 cases (73.3%). Adjusted trend by
      year showed a statistically significant decrease in mastectomy rates from 2005 to
      2010 (p = 0.003) with a progressive reduction of 4.24% per year. A multivariate
      model showed a statistically significant association of the following factors
      with mastectomy: age < 40 or >= 70 years, pTis, pT1mi, positive axillary nodes,
      lobular histology, tumour grade II and III, negative progesterone receptors and
      multiple lesions. CONCLUSION: Our study demonstrates that a high proportion of
      patients with newly diagnosed unilateral early-stage breast cancer from the
      eusomaDB underwent breast-conserving surgery. It also shows a significant trend
      of decreasing mastectomy rates from 2005 to 2010. Moreover, our study suggests
      mastectomy rates in the population from the eusomaDB are lower than those
      reported in the US.

PMID- 22483324
TI  - Comparison of the prevalence and changing resistance to nalidixic acid and
      ciprofloxacin of Shigella between Europe-America and Asia-Africa from 1998 to
      2009.
AB  - Shigella is becoming an increasing public health problem due to development of
      multiple antimicrobial resistance, frequently resulting in treatment failure. A
      systematic review was conducted based on a literature search of computerised
      databases. Random or fixed-effects models were used, based on the P-value
      considering the possibility of heterogeneity between studies, for meta-analysis.
      Statistical analyses were performed using STATA 10.0. In the area of Asia-Africa,
      resistance rates to nalidixic acid and ciprofloxacin were 33.6% [95% confidence
      interval (CI) 21.8-46.6%] and 5.0% (95% CI 2.8-7.8%), respectively, 10.5 and 16.7
      times those of Europe-America. Moreover, resistance to nalidixic acid and
      ciprofloxacin in Asia-Africa progressively increased each year, reaching 64.5%
      (95% CI 13.8-99.3%) and 29.1% (95% CI 0.9-74.8%), respectively, in 2007-2009,
      whilst isolates in Europe-America remained at low levels of resistance (<5.0% and
      <1.0%, respectively). All Shigella flexneri strains showed higher resistance than
      Shigella sonnei in Europe-America: overall, 3.5% (95% CI 1.4-6.4%) vs. 2.6% (95%
      CI 1.0-5.0%) resistant to nalidixic acid and 1.0% (95% CI 0.3-2.2%) vs. 0.1% (95%
      CI 0.0-0.3%) resistant to ciprofloxacin. In Asia-Africa, a similar trend was
      found for ciprofloxacin [3.0% (95% CI 1.4-5.3%) vs. 0.5% (95% CI 0.2-0.8%)],
      whereas the trend was reversed for nalidixic acid [32.6% (95% CI 14.5-53.9%) vs.
      44.3% (95% CI 26.9-62.5%). In conclusion, quinolone resistance in Shigella has
      increased at an alarming speed, reinforcing the importance of continuous
      monitoring of antimicrobial resistance in Shigella.

PMID- 22483325
TI  - Distinct chemotypes of Tephrosia vogelii and implications for their use in pest
      control and soil enrichment.
AB  - Tephrosia vogelii Hook. f. (Leguminosae) is being promoted as a pest control and
      soil enrichment agent for poorly-resourced small-scale farmers in southern and
      eastern Africa. This study examined plants being cultivated by farmers and found
      two chemotypes. Chemotype 1 (C1) contained rotenoids, including deguelin,
      rotenone, sarcolobine, tephrosin and alpha-toxicarol, required for pest control
      efficacy. Rotenoids were absent from chemotype 2 (C2), which was characterised by
      prenylated flavanones, including the previously unrecorded examples (2S)-5,7
      dimethoxy-8-(3-hydroxy-3-methylbut-1Z-enyl)flavanone, (2S)-5,7-dimethoxy-8-(3
      methylbut-1,3-dienyl)flavanone, (2S)-4'-hydroxy-5-methoxy-6",6"
      dimethylpyrano[2",3":7,8]flavanone, (2S)-5-methoxy-6",6"-dimethyl-4",5"
      dihydrocyclopropa[4",5"]furano[2",3":7,8]flavanone, (2S)-7-hydroxy-5-methoxy-8
      prenylflavanone, and (2R,3R)-3-hydroxy-5-methoxy-6",6"
      dimethylpyrano[2",3":7,8]flavanone. The known compounds (2S)-5-methoxy-6",6"
      dimethylpyrano[2",3":7,8]flavanone (obovatin 5-methyl ether) and 5,7-dimethoxy-8
      (3-hydroxy-3-methylbut-1Z-enyl)flavone (Z-tephrostachin) were also found in C2.
      This chemotype, although designated Tephrosia candida DC. in collections
      originating from the World Agroforestry Centre (ICRAF), was confirmed to be T.
      vogelii on the basis of morphological comparison with verified herbarium
      specimens and DNA sequence analysis. Sampling from 13 locations in Malawi where
      farmers cultivate Tephrosia species for insecticidal use indicated that almost 1
      in 4 plants were T. vogelii C2, and so were unsuitable for this application. Leaf
      material sourced from a herbarium specimen of T. candida contained most of the
      flavanones found in T. vogelii C2, but no rotenoids. However, the profile of
      flavonol glycosides was different to that of T. vogelii C1 and C2, with 6-hydroxy
      kaempferol 6-methyl ether as the predominant aglycone rather than kaempferol and
      quercetin. The structures of four unrecorded flavonol glycosides present in T.
      candida were determined using cryoprobe NMR spectroscopy and MS as the 3-O-alpha
      rhamnopyranosyl(1->6)-beta-galactopyranoside-7-O-alpha-rhamnopyranoside, 3-O
      alpha-rhamnopyranosyl(1->2)[alpha-rhamnopyranosyl(1->6)]-beta-galactopyranoside,
      3-O-alpha-rhamnopyranosyl(1->2)[alpha-rhamnopyranosyl(1->6)]-beta
      galactopyranoside-7-O-alpha-rhamnopyranoside, and 3-O-alpha-rhamnopyranosyl(1
      >2)[(3-O-E-feruloyl)-alpha-rhamnopyranosyl(1->6)]-beta-galactopyranosides of 6
      hydroxykaempferol 6-methyl ether. Tentative structures for a further 37 flavonol
      glycosides of T. candida were assigned by LC-MS/MS. The correct chemotype of T.
      vogelii (i.e. C1) needs to be promoted for use by farmers in pest control
      applications.

PMID- 22483326
TI  - Transcatheter aortic valve replacement: outcomes of patients with moderate or
      severe mitral regurgitation.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of mitral
      regurgitation (MR) on outcomes after transcatheter aortic valve replacement
      (TAVR) and the impact of TAVR on MR. BACKGROUND: Little is known of the influence
      of MR on outcomes after TAVR. METHODS: The outcomes of patients with mild or less
      (n = 319), moderate (n = 89), and severe (n = 43) MR were evaluated after TAVR at
      2 Canadian centers. RESULTS: Patients with moderate or severe MR had a higher
      mortality rate than those with mild or less MR during the 30 days after TAVR
      (adjusted hazard ratio: 2.10; 95% confidence interval: 1.12 to 3.94; p = 0.02).
      However, the mortality rates after 30 days were similar (adjusted hazard ratio:
      0.82; 95% confidence interval: 0.50 to 1.34; p = 0.42). One year after TAVR,
      moderate MR had improved in 58%, remained moderate in 17%, and worsened to severe
      in 1%, and 24% of patients had died. Severe MR had improved in 49% and remained
      severe in 16%, and 35% of patients had died. Multivariate predictors of improved
      MR at 1 year (vs. unchanged MR, worse MR, or death) were a mean transaortic
      gradient >= 40 mm Hg, functional (as opposed to structural) MR, the absence of
      pulmonary hypertension, and the absence of atrial fibrillation. CONCLUSIONS:
      Moderate or severe MR in patients undergoing TAVR is associated with a higher
      early, but not late, mortality rate. At 1-year follow-up, MR was improved in 55%
      of patients with moderate or severe MR at baseline. Improvement was more likely
      in patients with high transaortic gradients, with functional MR, without
      pulmonary hypertension and without atrial fibrillation.

PMID- 22483327
TI  - Quantification and impact of untreated coronary artery disease after percutaneous
      coronary intervention: the residual SYNTAX (Synergy Between PCI with Taxus and
      Cardiac Surgery) score.
AB  - OBJECTIVES: The purpose of this study was to quantify the extent and complexity
      of residual coronary stenoses following percutaneous coronary intervention (PCI)
      and to evaluate its impact on adverse ischemic outcomes. BACKGROUND: Incomplete
      revascularization (IR) after PCI is common, and most studies have suggested that
      IR is associated with a worse prognosis compared with complete revascularization
      (CR). However, formal quantification of the extent and complexity of residual
      atherosclerosis after PCI has not been performed. METHODS: The baseline Synergy
      Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (bSS) from 2,686
      angiograms from patients with moderate- and high-risk acute coronary syndrome
      (ACS) undergoing PCI enrolled in the prospective ACUITY (Acute Catheterization
      and Urgent Intervention Triage Strategy) trial was determined. The SS after PCI
      was also assessed, generating the "residual" SS (rSS). Patients with rSS >0 were
      defined as having IR and were stratified by rSS tertiles, and their outcomes were
      compared to the CR group. RESULTS: The bSS was 12.8 +/- 6.7, and after PCI the
      rSS was 5.6 +/- 2.2. Following PCI, 1,084 patients (40.4%) had rSS = 0 (CR), 523
      (19.5%) had rSS >0 but <=2, 578 (21.5%) had rSS >2 but <=8, and 501 patients
      (18.7%) had rSS >8. Age, insulin-treated diabetes, hypertension, smoking,
      elevated biomarkers or ST-segment deviation, and lower ejection fraction were
      more frequent in patients with IR compared with CR. The 30-day and 1-year rates
      of ischemic events were significantly higher in the IR group compared with the CR
      group, especially those with high rSS. By multivariable analysis, rSS was a
      strong independent predictor of all ischemic outcomes at 1 year, including all
      cause mortality (hazard ratio: 1.05, 95% confidence interval: 1.02 to 1.09, p =
      0.006). CONCLUSIONS: The rSS is useful to quantify and risk-stratify the degree
      and complexity of residual stenosis after PCI. Specifically, rSS >8.0 after PCI
      in patients with moderate- and high-risk ACS is associated with a poor 30-day and
      1-year prognosis. (Comparison of Angiomax Versus Heparin in Acute Coronary
      Syndromes; NCT00093158).

PMID- 22483329
TI  - Palladium-catalyzed C-H alkenylation of arenes using thioethers as directing
      groups.
AB  - Thioethers have been proven to be reliable directing groups for palladium
      catalyzed alkenylation of arenes via C-H activation. Mechanistic investigation
      reveals that the C-H cleavage of arenes is the turnover-limiting step, and an
      acetate-bridged dinuclear cyclopalladation intermediate is involved. The
      alkenylated thioethers can be easily removed and transformed into a variety of
      useful groups.

PMID- 22483328
TI  - Iron sulfur cluster proteins and microbial regulation: implications for
      understanding tuberculosis.
AB  - All pathogenic and nonpathogenic microbes are continuously exposed to
      environmental or endogenous reactive oxygen and nitrogen species, which can
      critically effect survival and disease. Iron-sulfur [Fe-S] cluster containing
      prosthetic groups provide the microbial cell with a unique capacity to sense and
      transcriptionally respond to diatomic gases (e.g. NO and O2) and redox-cycling
      agents. Recent advances in our understanding of the mechanisms for how the FNR
      and SoxR [Fe-S] cluster proteins respond to NO and O2 have provided new insights
      into the biochemical mechanism of action of the Mycobacterium tuberculosis (Mtb)
      family of WhiB [Fe-S] cluster proteins. These insights have provided the basis
      for establishing a unifying paradigm for the Mtb WhiB family of proteins. Mtb is
      the etiological agent for tuberculosis (TB), a disease that affects nearly one
      third of the world's population.

PMID- 22483330
TI  - Day 22 of induction therapy is important for minimal residual disease assessment
      by flow cytometry in childhood acute lymphoblastic leukemia.
AB  - This study was aimed to illustrate the significance of minimal residual disease
      (MRD) assessment on day 22 in childhood acute lymphoblastic leukemia. MRD were
      measured on day 22, day 36, week 12, month 6 and month 12 by four-color flow
      cytometry. The 5-year cumulative incidence of relapse was significantly different
      for patients with MRD levels of <0.01%, 0.01-0.1%, 0.1-1.0% and >= 1.0% on day
      22: 6.9 +/- 2.6%, 16.7 +/- 5.5%, 25.8 +/- 6.2% and 58.4 +/- 13.4% (P < 0.001).
      MRD on day 22 was more powerful than other parameters including NCI risk.
      However, other time points after induction, although predictive as well, were not
      accurate enough due to false positivity.

PMID- 22483331
TI  - UPLC-MS/MS determination of ractopamine residues in retinal tissue of treated
      food-producing pigs.
AB  - Ractopamine is a beta(2)-adrenergic agonist, which reduces fat deposition and
      promotes muscle growth in animals for meat production. In the European Union
      countries, systematic monitoring and control of this contaminant residue is
      regularly performed by use of validated analytical methods of detection in
      different biological materials. The aim of the present study was to assess
      persistence of ractopamine in retina as a pigmented tissue by determination of
      its residues using UPLC-MS/MS as a quantitative confirmatory method after pig
      exposure to a ractopamine dose of 0.51 mg/kg b.w. Experimental group (n=9) of
      pigs were orally administered ractopamine for 28 days and then randomly
      sacrificed (n=3) on days 1, 3 and 8 of treatment discontinuation, whereas control
      animals (n=3) were left untreated. Study results showed mean ractopamine residue
      concentrations of 110.36 MUg/kg, 67.11 MUg/kg and 89.93 MUg/kg on days 1, 3 and 8
      after withdrawal, respectively, indicating high accumulation of ractopamine in
      retina despite a low dose applied. These data pointed to high affinity of
      ractopamine for binding to the pigmented segment of the eye, thus supporting the
      use of pigmented tissues as matrices in the regulatory monitoring of this beta(2)
      adrenergic agonist.

PMID- 22483332
TI  - Ultra sensitive measurement of endogenous epinephrine and norepinephrine in human
      plasma by semi-automated SPE-LC-MS/MS.
AB  - Measurement of endogenous epinephrine (E) and norepinephrine (NE) in human plasma
      is very challenging due to lower endogenous concentrations as compared with
      animal plasma. An LC-MS/MS in combination with alumina-based SPE and
      derivatization procedure was validated for the measurement of E and NE in human
      plasma with acceptable intra-day and inter-day accuracy and precision. Sample was
      extracted with semi-automated alumina 96-well solid phase extraction (SPE)
      cartridge. The resulting eluent was dried and derivatized using d4-acetaldehyde.
      The analytes were separated on a monolithic C(18) column. Extraction efficiencies
      were >66% for E and NE. The lower limit of quantitation (LLOQ) was 5.00 pg/mL for
      E and 20.0 pg/mL for NE.

PMID- 22483333
TI  - Direct binding of boar ejaculate and epididymal spermatozoa to porcine epididymal
      epithelial cells is also needed to maintain sperm survival in in vitro co
      culture.
AB  - The aim of the present study was to compare the influence of cultured epididymal
      epithelial cells (EEC) from corpus, caput or cauda, oviductal epithelial cells
      (OEC) and non-reproductive epithelial cells (LLC-PK1) on function and survival of
      epididymal and ejaculated spermatozoa, in the latter case to determine whether
      such influence differed between morphologically normal and abnormal spermatozoa.
      For this purpose, either spermatozoa were directly co-cultured with EEC from
      caput, corpus, or cauda, OEC and LLC-PK1 cells (experiment 1) or a membrane
      diffusible insert was included in these co-cultures (experiment 2). EEC cultured
      from the three epididymal regions did not differently affect the sperm
      parameters. Morphologically normal spermatozoa presented a higher ability to bind
      EEC, OEC, and LLC-PK1 than abnormal spermatozoa with cytoplasmic droplets or with
      tail/head malformations. Epididymal spermatozoa were more able to bind EEC during
      the first 24 h of co-culture, while ejaculated spermatozoa presented a higher
      capacity to bind OEC between 30 min and 3 h of co-incubation. In all cases, the
      ability to bind to epithelial cells was higher when they were co-cultured with
      EEC and OEC than with LLC-PK1. After 2 h of co-culture, the viability of
      epididymal spermatozoa was better maintained when they bound EEC than when they
      bound OEC. Conversely, the viability of ejaculated spermatozoa was better
      maintained when bound OEC than when bound EEC after 24 and 48 h of co-culture.
      Our work, apart from corroborating the involvement of morphologically normal
      spermatozoa in the formation of sperm reservoir, highlights the importance of
      direct contact spermatozoa-EEC in maintaining the sperm survival in in vitro co
      culture, and also suggests that a specific binding between EEC and epididymal
      spermatozoa exists.

PMID- 22483334
TI  - Design and "in vivo" evaluation of two adapted catheters for intrauterine
      transcervical insemination in sheep.
AB  - In order to obtain better fertility, we evaluated two ovine artificial
      insemination (AI) catheters that were manufactured according to the anatomical
      structure of the ewe cervix. Morphometric data of the cervix in Churra and Assaf
      breeds were used to design two types of curved catheters: CAT06 with one
      curvature and ZIGZAG with five curvatures in a zigzag shape. Two commercial
      catheters (IMV((r)) and Minitub((r))) were used as controls. In experiment 1,
      cervical penetration and the degree of reflux were measured in a Cervical AI
      simulated assay both Churra (n=28) and Assaf ewes (n=28). In experiment 2, a
      fertility study was performed with three catheters (only one commercial control
      catheter - IMV) in 465 inseminations (Assaf); and a second study analyzed only
      the top two catheters (IMV and CAT06) in 428 inseminations (210 Assaf and 218
      Churra). The ewes were synchronized using intravaginal sponges (40 FGA mg during
      14 days) and 500 IU of eCG. Deeper penetration of the cervix was obtained with
      the new catheters compared with the commercial ones (1.5, 1.3, 3.5 and 3.2 cm for
      the IMV, Minitub, CAT06 and ZIGZAG catheters, respectively). The cervical
      penetration and the reflux grade of each catheter showed no differences between
      breeds. In experiment 2, the degree of penetration had no correlation with
      fertility of different catheters. The best percentage of lambing ewes was
      obtained with the IMV and CAT06 catheters (39.5 and 48.1%, respectively. vs 27.2%
      for ZIGZAG catheter, in the Assaf breed). Regarding effect of breed, Assaf (39.3%
      and 49.5 for IMV and CAT06, respectively) showed better lambing rates than Churra
      (29.0% and 39.0%, respectively), and the CAT06 catheter showed significantly
      higher rates for each breed.

PMID- 22483335
TI  - Roughness assessment and wetting behavior of fluorocarbon surfaces.
AB  - The wetting behavior of fluorocarbon materials has been studied with the aim of
      assessing the influence of the surface chemical composition and surface roughness
      on the water advancing and receding contact angles. Diamond like carbon and two
      fluorocarbon materials with different fluorine content have been prepared by
      plasma enhanced chemical vapor deposition and characterized by X-ray
      photoemission, Raman and FT-IR spectroscopies. Very rough surfaces have been
      obtained by deposition of thin films of these materials on polymer substrates
      previously subjected to plasma etching to increase their roughness. A direct
      correlation has been found between roughness and water contact angles while a
      superhydrophobic behavior (i.e., water contact angles higher than 150 degrees 
      and relatively low adhesion energy) was found for the films with the highest
      fluorine content deposited on very rough substrates. A critical evaluation of the
      methods currently used to assess the roughness of these surfaces by atomic force
      microscopy (AFM) has evidenced that calculated RMS roughness values and actual
      surface areas are quite dependent on both the scale of observation and image
      resolution. A critical discussion is carried out about the application of the
      Wenzel model to account for the wetting behavior of this type of surfaces.

PMID- 22483336
TI  - The "safe" triangle, contrast material, and particulate steroids in lumbar
      transforaminal injections: What are the right things to do?

PMID- 22483337
TI  - Coenzyme Q10 levels in beta-thalassemia and its association with ferritin levels
      and chelation therapy.
AB  - The aim of this study was to evaluate the plasma coenzyme Q(10) (CoQ(10))
      concentration, a vitamin-like substance found in every cell, which is also viewed
      as the most effective membrane antioxidant, of thalassemic patients and
      investigate the effect of chelating agents and ferritin levels on its
      concentration in patients with beta-thalassemia major (beta-TM). The study
      included 44 beta-TM patients undergoing deferasirox (DFRA) or deferoxamine (DFO)
      chelation monotherapies or combined therapy with deferiprone (L1) and DFO, 20
      patients with beta-thalassemia (beta-thal) traits and a control group of 22
      healthy sex- and age-matched subjects. Complete blood counts, liver and renal
      function tests, lipid profiles, ferritin and plasma CoQ(10) [by high performance
      liquid chromatography (HPLC)] were analyzed. The mean age (14.7 +/- 7.3 years;
      median 14.3 years) and sex (26 males, 18 females) of the beta-TM patients were
      not statistically different from the beta-thal trait patients and the control
      group. The plasma CoQ(10) concentration was 0.425 +/- 0.136 MUmol/L in beta-TM
      patients, 0.508 +/- 0.159 MUmol/L in the beta-thal trait patients and 0.534 +/-
      0.133 MUmol/L in the control group. The difference was significant in both the
      beta-TM (p < 0.001) and beta-thal trait patients (p <0.05) compared to the
      control group. The CoQ(10) concentration was also associated with ferritin levels
      in beta-TM patients; the beta-TM patients with high ferritin levels had a lower
      CoQ(10) (p <0.05) concentration. Also, higher plasma CoQ(10) levels were detected
      in beta-TM patients undergoing DFRA treatment, according to combined therapy
      administered (0.457 +/- 0.115 vs. 0.382 +/- 0.127 mg/dL respectively, p <0.05).
      In conclusion, both the beta-thal trait and beta-TM patients have lower
      antioxidant capacity as demonstrated by the lower CoQ(10) levels. The type of
      chelating agents and ferritin levels are factors effecting CoQ(10) concentration
      in beta-TM patients.

PMID- 22483338
TI  - Structural analysis of the O-specific polysaccharide from the lipopolysaccharide
      of Aeromonas veronii bv. sobria strain K49.
AB  - The O-specific polysaccharide obtained by mild-acid degradation of the
      lipopolysaccharide from Aeromonas veronii bv. sobria strain K49 was studied by
      sugar and methylation analyses along with (1)H and (13)C NMR spectroscopy. The
      sequence of the sugar residues was determined using (1)H,(1)H NOESY and
      (1)H,(13)C HMBC experiments. The O-specific polysaccharide was found to be a high
      molecular mass polysaccharide composed of repeating units of the structure: ->2)
      beta-D-Quip3NAc-(1->3)-alpha-L-Rhap-(1->3)-alpha-L-Rhap-(1->2)-alpha-L-Rhap-(1
      >3)-alpha-D-FucpNAc-(1-> ESI MS confirmed the pentasaccharide structure of the
      repeating unit, as the molecular mass peaks seen in the spectrum differed by
      812.34 u, a value corresponding to the calculated molecular mass of the O-unit.

PMID- 22483339
TI  - Serum oxidized low-density lipoprotein level and risk of cognitive impairment in
      older women.
AB  - We investigated the association between serum level of oxidized low-density
      lipoprotein (oxLDL) and risk of cognitive impairment (dementia or mild cognitive
      impairment) among 572 nondemented community-dwelling women from a prospective
      cohort study of aging. After 5 years of follow-up, 228 (39.9%) developed
      cognitive impairment; and this did not differ by tertile of baseline oxLDL level
      (highest compared with lowest tertile 38.2% vs. 39.5%; odds ratio, 0.90; 95%
      confidence interval, 0.63-1.43). Multivariate adjustment produced similar results
      (odds ratio, 0.91; 95% confidence interval, 0.60-1.39). These findings suggest
      that increased levels of serum oxLDL are not associated with a greater risk of
      incident cognitive impairment in older women.

PMID- 22483340
TI  - Effects of long-term chronic exposure to radionuclides in plant populations.
AB  - The results of field studies carried out on different plant species (winter rye
      and wheat, spring barley, oats, Scots pine, wild vetch, crested hairgrass) in
      various radioecological situations (nuclear weapon testing, the Chernobyl
      accident, uranium and radium processing) to investigate the effects of long-term
      chronic exposure to radionuclides are discussed. Plant populations growing in
      areas with relatively low levels of pollution are characterized by an increased
      level of both cytogenetic disturbances and genetic diversity. Although ionizing
      radiation causes primary damage at the molecular level, there are emergent
      effects at the level of populations, non-predictable from the knowledge of
      elementary mechanisms of cellular effects formation. Accumulation of cellular
      alterations may afterward influence biological parameters important for
      populations such as health and reproduction. Presented data provide evidence that
      in plant populations inhabiting heavily contaminated territories cytogenetic
      damage could be accompanied by a decrease in reproductive capacity. However, in
      less contaminated sites, because of the scarcity of data available, a steady
      relationship between cytogenetic effects and reproductive capacity was not
      revealed. Under radioactive contamination of the plant's environment, a
      population's resistance to exposure may increase. However, there are
      radioecological situations where an enhanced radioresistance has not evolved or
      has not persisted.

PMID- 22483341
TI  - Tumefactive multiple sclerosis requiring emergent biopsy and histological
      investigation to confirm the diagnosis: a case report.
AB  - INTRODUCTION: Tumefactive multiple sclerosis is a demyelinating disease that
      demonstrates tumor-like features on magnetic resonance imaging. Although
      diagnostic challenges without biopsy have been tried by employing radiological
      studies and cerebrospinal fluid examinations, histological investigation is still
      necessary for certain diagnosis in some complicated cases. CASE PRESENTATION: A
      37-year-old Asian man complaining of mild left leg motor weakness visited our
      clinic. Magnetic resonance imaging demonstrated high-signal lesions in bilateral
      occipital forceps majors, the left caudate head, and the left semicentral ovale
      on fluid-attenuated inversion recovery and T2-weighted imaging, and these lesions
      were enhanced by gadolinium-dimeglumin. Tumefactive multiple sclerosis was
      suspected because the enhancement indistinctly extended along the corpus callosum
      on magnetic resonance imaging and scintigraphy showed a low malignancy of the
      lesions. But oligoclonal bands were not detected in cerebrospinal fluid. In a few
      days, his symptoms fulminantly deteriorated with mental confusion and left
      hemiparesis, and steroid pulse therapy was performed. In spite of the treatment,
      follow-up magnetic resonance imaging showed enlargement of the lesions.
      Therefore, emergent biopsy was performed and finally led to the diagnosis of
      demyelinating disease. The enhanced lesion on magnetic resonance imaging
      disappeared after one month of prednisolone treatment, but mild disorientation
      and left hemiparesis remained as sequelae. CONCLUSIONS: Fulminant aggravation of
      the disease can cause irreversible neurological deficits. Thus, an early decision
      to perform a biopsy is necessary for exact diagnosis and appropriate treatment if
      radiological studies and cerebrospinal fluid examinations cannot rule out the
      possibility of brain tumors.

PMID- 22483342
TI  - Using the "visual target grip test" to identify sincerity of effort during grip
      strength testing.
AB  - We devised a sincerity of effort assessment based on "tricking" a person into
      exerting maximal effort by providing incorrect visual feedback. The assessment
      involves deriving a target line from nonvisual peak gripping force, instructing
      participants to reach it with each grip repetition, and then secretly changing
      its position, which requires doubling the force necessary to reach it.
      Accordingly, participants are tricked into exerting more force than intended to
      reach the deceptive target line. We examined the validity of this test by
      comparing force values between "trick" and "non-trick" trials in 30 healthy
      participants. The study design used was a prospective cohort. Providing incorrect
      visual feedback caused significantly greater increases in force during submaximal
      effort (69%) than during maximal effort (28%). This test effectively detected
      submaximal effort (sensitivity=0.83 and specificity=0.93). Although this test is
      not safe for patients during initial therapy, it may be appropriate for patients
      who can safely exert maximal grip force. LEVEL OF EVIDENCE: Not applicable.

PMID- 22483343
TI  - Intramandibular course of the mandibular nerve; clinical significance for
      distraction and implantology.
AB  - OBJECTIVE: Loss of teeth is accompanied with loss of function and therefore
      reduction of alveolar bone height. Insufficient bone height can jeopardize the
      anchorage of implants or surgical procedures such as distraction osteogenesis,
      because of possible mandibular nerve damage. The goal of this investigation was
      to determine the exact course of the intramandibular nerve in edentulous
      mandibles. MATERIAL AND METHOD: The study samples included 37 dry human
      edentulous mandibles. A dental CT scan analysis was performed and four cross
      sectional views were investigated for each mandible. The Cawood classification
      was used to assess the grade of atrophy. Implantation simulation was performed in
      every case. RESULTS: There was no bilateral symmetry in edentulous mandibles,
      whatever the cross-section studied. A rate of 38.7% were classified Cawood class
      IV, the most common group in edentulous patients. Our study results led us to
      place the distraction osteogenesis device in the posterior edentulous mandible.
      Implant placement was not possible in every case. DISCUSSION: Our findings allow
      better understanding from the pathway of the mandibular canal close to the first
      and second molar in edentulous mandibles. This anatomical data and surgical
      techniques such as implant insertion and distraction osteogenesis allow finding
      solutions for "mandibular edentulism". Distraction is essential for a successful
      implantology.

PMID- 22483344
TI  - Beckwith-Wiedemann syndrome, delayed abdominal wall closure, and neonatal
      intussusception--case report and literature review.
AB  - We present the extremely rare case of a male newborn with Beckwith-Wiedemann
      Syndrome (BWS) presenting as delayed abdominal wall closure and neonatal
      intussusception. Fetal ultrasound had shown omphalocele that resolved
      spontaneously. When feeding was attempted, he had various episodes of vomiting.
      An x-ray showed signs of high bowel obstruction. Jejunal intussusception was
      found on laparotomy. Enterectomy and primary jejuno-jejunal anastomosis was
      performed. During post-operative period subtle physical findings became
      prominent: plain hemangioma, posterior helical indentations, and macroglossia.
      Cardiac ultrasonography showed a patent foramen oval with small left-to-right
      shunt. Ultrasonography showed renal hyperplasia. Genetic study showed
      hypomethylation of DMR2 region of 11p15 chromosome.

PMID- 22483345
TI  - Sequence-defined glycopolymer segments presenting mannose: synthesis and lectin
      binding affinity.
AB  - We present for the first time the synthesis of sequence-defined monodisperse
      glycopolymer segments via solid-phase polymer synthesis. Functional building
      blocks displaying alkyne moieties and hydrophilic ethylenedioxy units were
      assembled stepwise on solid phase. The resulting polymer segments were conjugated
      with mannose sugars via 1,3-dipolar cycloaddition. The obtained mono-, di-, and
      trivalent mannose structures were then subject to Con A lectin binding. Surface
      plasmon resonance studies showed a nonlinear increase in binding regarding the
      number and spacing of sugar ligands. The results of Con A lectin binding assays
      indicate that the chemical composition of the polymeric scaffold strongly
      contributes to the binding activities as well as the spacing between the ligands
      and the number of presented mannose units. Our approach now allows for the
      synthesis of highly defined glycooligomers and glycopolymers with a diversity of
      properties to investigate systematically multivalent effects of polymeric
      ligands.

PMID- 22483346
TI  - Solution composition impacts fibronectin immobilization on carboxymethyl-dextran
      surfaces and INS-1 insulin secretion.
AB  - It is shown that solution composition during immobilization plays a critical role
      in the properties of fibronectin (FN) surfaces and their bioactivity towards
      insulinoma (INS-1) cell function. X-ray photoelectron spectroscopy revealed FN
      grafting onto low-fouling carboxymethyl-dextran (CMD) surfaces was successful
      with solutions composed of 10 MUM CaCl(2), 10 MUM MgCl(2), 10 MUM MnCl(2), and 10
      MUM and 1mM NaCl, but unsuccessful with those made of 150 mM NaCl or 1* PBS.
      Circular dichroism and photon correlation spectroscopy revealed that regardless
      of solution composition, no measurable differences in free FN conformation
      prevail. AFM imaging of FN-CMD revealed, while there are no quantitative
      differences in surface roughness, there are some subtle qualitative differences
      in topography. FN surface immobilization scheme does not influence INS-1 cell
      growth after 3 and 7 days regardless of the underlying substrate or solution
      composition. INS-1 cell insulin secretion in response to glucose is affected by
      the substrate and solution composition during FN immobilization.

PMID- 22483347
TI  - Novel route for rapid biosynthesis of copper nanoparticles using aqueous extract
      of Calotropis procera L. latex and their cytotoxicity on tumor cells.
AB  - This paper accounts for novel, low-cost, eco-friendly route for rapid
      biosynthesis of copper nanoparticles. Cysteine proteases present in the latex of
      Calotropis procera L. were used to fabricate copper nanoparticles from copper
      acetate. Copper nanoparticles were initially characterized by transmission
      electron microscopy (TEM) and X-ray diffraction technique (XRD). Transmission
      electron microscopy (TEM) was used to estimate the size and shape of
      nanoparticles. The average size of copper nanoparticles was found to be 15 +/-
      1.7 nm. Energy dispersive analysis of X-rays (EDAX) showed distinct peaks of
      copper. Fourier transform infrared spectroscopy (FTIR) was performed to confirm
      capping behavior of the latex proteins that contributed to long term stability of
      copper nanoparticles (6 months) in aqueous medium. Copper nanoparticles
      synthesized by above method were monodisperse type. Cytotoxicity studies of latex
      stabilized copper nanoparticles were carried out on HeLa, A549 and BHK21 cell
      lines by MTT dye conversion assay. HeLa, A549 and BHK21 cells showed excellent
      viability even at 120 MUM concentration of copper nanoparticles. This shows that
      copper nanoparticles synthesized by above method hold excellent biocompatibility.

PMID- 22483348
TI  - Forming microbial anodes under delayed polarisation modifies the electron
      transfer network and decreases the polarisation time required.
AB  - Microbial anodes were formed from compost leachate on carbon cloth electrodes.
      The biofilms formed at the surface of electrodes kept at open circuit contained
      microorganisms that switched their metabolism towards electrode respiration in
      response to a few minutes of polarisation. When polarisation at -0.2 V/SCE (+0.04
      V/SHE) was applied to a pre-established biofilm formed at open circuit (delayed
      polarisation), the bacteria developed an extracellular electron transport network
      that showed multiple redox systems, reaching 9.4 A/m(2) after only 3-9 days of
      polarisation. In contrast, when polarisation was applied from the beginning,
      bacteria developed a well-tuned extracellular electron transfer network
      concomitantly with their growth, but 36 days of polarisation were required to get
      current of the same order (6-8 A/m(2)). The difference in performance was
      attributed to the thinner, more heterogeneous structure of the biofilms obtained
      by delayed polarisation compared to the thick uniform structure obtained by full
      polarisation.

PMID- 22483349
TI  - Graphene/carbon cloth anode for high-performance mediatorless microbial fuel
      cells.
AB  - Graphene was electrochemically deposited on carbon cloth to fabricate an anode
      for a Pseudomonas aeruginosa mediatorless microbial fuel cell (MFC). The graphene
      modification improved power density and energy conversion efficiency by 2.7 and 3
      times, respectively. The improvement is attributed to the high biocompatibility
      of graphene which promotes bacteria growth on the electrode surface that results
      in the creation of more direct electron transfer activation centers and
      stimulates excretion of mediating molecules for higher electron transfer rate. A
      parallel bioelectrocatalytic mechanism consisting of simultaneous direct electron
      transfer and cell-excreted mediator-enabled electron transfer was established in
      the P. aeruginosa-catalyzed MFC. This study does not only offer fundamental
      insights into MFC reactions, but also suggests a low cost manufacturing process
      to fabricate high power MFCs for practical applications.

PMID- 22483350
TI  - Reduction of formic acid to methanol under hydrothermal conditions in the
      presence of Cu and Zn.
AB  - Formic acid is the main breakdown product of mild hydrothermal treatment of
      carbohydrates. Further conversion to methanol was achieved using Cu as catalyst
      and Zn as reductant under hydrothermal conditions of 250-325  degrees C for 3-12
      h. Both Cu and Zn used were commercial Cu and Zn powders with particle sizes of
      200 mesh. A methanol yield of 32% was achieved at 300  degrees C for 5h with 6.5
      mmol of Cu, 12 mmol of Zn and a filling rate of 44%. Thus, this process may
      provide a promising solution to producing methanol from biomass by converting
      carbohydrates into formic acid.

PMID- 22483351
TI  - Whole-cell based solvent-free system for one-pot production of biodiesel from
      waste grease.
AB  - A whole-cell based solvent-free system was developed for efficient conversion of
      waste grease to biodiesel via one-pot esterification and transesterification. By
      isolation and screening of lipase-producing strains from soil, Serratia
      marcescens YXJ-1002 was discovered for the biotransformation of grease to
      biodiesel. The lipase (SML) from this strain was cloned and expressed in
      Escherichia coli as an intracellular enzyme, showing 6 times higher whole-cell
      based hydrolysis activity than that of wild type strain. The recombinant cells
      were used for biodiesel production from waste grease in one-pot reactions
      containing no solvent with the addition of methanol in several small portions,
      and 97% yield of biodiesel (FAME) was achieved under optimized conditions. In
      addition, the whole-cell biocatalysts showed excellent reusability, retaining 74%
      productivity after 4 cycles. The developed system, biocatalyst, and process
      enable the efficient, low-cost, and green production of biodiesel from waste
      grease, providing with a potential industrial application.

PMID- 22483352
TI  - Superhydrophobicity and liquid repellency of solutions on polypropylene.
AB  - The sliding of drops of aqueous solutions of organic liquids over a
      superhydrophobic polypropylene (SH-PP) surface has been studied experimentally.
      The multi-scale roughness of this surface is intrinsically inhomogeneous. Careful
      analysis of the wettability of each solution enables us to establish the
      statistics of the advancing and receding contact angles. We consider a threshold
      value of the receding static contact angle, above which drop sliding and rebound
      are facilitated as the criterion for superhydrophobicity. The percentage of
      receding contact angles greater than this threshold is then used as a practical
      index of superhydrophobicity (SHI). The variation of the SHI is compared with
      surface tension of the solution and various wetting parameters. A linear
      correlation is found between the SHI and the work of wetting defined by
      gamma(LG)costheta(0) where gamma(LG) is the surface tension of the solution and
      theta(0) is the static contact angle of the solution over the corresponding
      smooth surface. Such a correlation can be used as a predictive tool of the
      superhydrophobicity of a given surface with various liquids.

PMID- 22483353
TI  - The kissing-stent technique for treatment of distal aortic stenosis and
      protection of the inferior mesenteric artery orifice.
AB  - Focal infrarenal aortic stenosis is relatively rare. Traditionally, aortic
      endarterectomy and aortic bypass surgery have been used to treat these lesions.
      However, percutaneous transluminal angioplasty and stenting have become well
      defined alternatives. A 62-year-old woman presented with bilateral ischemic rest
      pain. Angiography revealed a mid-infrarenal aortic stenosis adjacent to an
      enlarged, patent inferior mesenteric artery. Celiac artery and superior
      mesenteric artery stenoses were also present. The kissing-stent technique is a
      viable option for ensuring inferior mesenteric artery patency when treating
      distal aortic lesions by endovascular means in patients with asymptomatic
      multivessel mesenteric artery disease.

PMID- 22483354
TI  - Influence of high-heeled shoes on venous function in young women.
AB  - BACKGROUND: Walking with high-heeled shoes is a common cause of venous complaints
      such as pain, fatigue, and heavy-feeling legs. The aim of the study was to
      clarify the influence of high-heeled shoes on the venous return and test the
      hypothesis that women wearing different styles of high-heeled shoes present an
      impaired venous return when compared with their values when they are barefoot.
      METHODS: Thirty asymptomatic women (mean age, 26.4 years) wearing appropriately
      sized shoes were evaluated by air plethysmography (APG), a test that measures
      changes in air volume on a cuff placed on the calf, while they performed
      orthostatic flexion and extension foot movements and altered standing up and
      lying down. The test was repeated in four situations: barefoot (0 cm), medium
      heels (3.5 cm), stiletto high heels (7 cm), and platform high heels (7 cm). The
      APG values of venous filling index (VFI), ejection fraction (EF), and residual
      volume fraction (RVF) were divided into four groups according to heel height and
      compared by repeated-measures analysis of variance. RESULTS: RVF was increased in
      the groups wearing high heels (stiletto and platform) compared with the barefoot
      group (P < .05). RVF was increased in the medium-heel group (3.5 cm) compared
      with the barefoot group (P < .05), and despite the lack of statistical
      significance, the medium-heel group showed lower values of RVF compared with the
      two high-heel groups. The EF parameter followed the opposite tendency, showing
      higher values for the barefoot group compared with the other three groups (P <
      .05). Values for VFI were similar in the three situations evaluated. CONCLUSIONS:
      High heels reduce muscle pump function, as demonstrated by reduced EF and
      increased RVF values. The continuous use of high heels tends to provoke venous
      hypertension in the lower limbs and may represent a causal factor of venous
      disease symptoms.

PMID- 22483355
TI  - Might infection explain the higher risk of coronary heart disease in South
      Asians? Systematic review comparing prevalence rates with white populations in
      developed countries.
AB  - OBJECTIVES: South Asians in developed countries such as the UK are at
      comparatively high risk of coronary heart disease for reasons which are not fully
      understood. One unexplored hypothesis is more infections in this ethnic group.
      This study assessed whether the prevalence of infections among South Asians
      differs from that among White populations of European origin in developed
      countries. STUDY DESIGN: Systematic review. METHODS: Medline, Web of Science and
      Google Scholar databases were searched. In addition, reference lists and
      citations were reviewed. RESULTS: Twenty-one studies reported prevalence rates
      and mean antibody levels of infection with 17 different pathogens or non-specific
      markers of infection. Among bacterial infections, higher rates of Escherichia
      coli and Mycobacterium tuberculosis infection were found in South Asians. No
      consistent differences were found for periodontal pathogens, Helicobacter pylori,
      Staphylococcus aureus, Chlamydia pneumoniae and Mycobacterium avium. For viral
      pathogens, higher rates of hepatitis A, hepatitis B and cytomegalovirus; and
      lower rates of herpes simplex, hepatitis C, human immunodeficiency virus and
      varicella zoster virus were found among South Asians. No difference was seen in
      the prevalence of hepatitis G virus in South Asians. Levels of non-specific
      markers of infection (total immunoglobulin G, endotoxin) were higher in South
      Asians. CONCLUSIONS: The number of studies was small. Differences in the
      prevalence of specific infections were found, but the current evidence is
      insufficient to support or reject the hypothesis under examination. Further
      studies are warranted.

PMID- 22483356
TI  - Tellurium-nanowire-coated glassy carbon electrodes for selective and sensitive
      detection of dopamine.
AB  - Tellurium-nanowire-coated glassy carbon electrodes (TNGCEs) have been fabricated
      and employed for selective and sensitive detection of dopamine (DA). TNGCEs were
      prepared by direct deposition of tellurium nanowires, 600 +/- 150 nm in length
      and 16 +/- 3 nm in diameter, onto glassy carbon electrodes, which were further
      coated with Nafion to improve their selectivity and stability. Compared to the
      GCE, the TNGCE is more electroactive (by approximately 1.9-fold) for DA, and its
      selectivity toward DA over ascorbic acid (AA) and uric acid (UA) is also greater.
      By applying differential pulse voltammetry, at a signal-to-noise ratio of 3, the
      TNGCE provides a limit of detection of 1 nM for DA in the presence of 0.5mM AA
      and UA. Linearity (R(2)=0.9955) of the oxidation current at 0.19 V against the
      concentration of DA is found over the range 5 nM-1 MUM. TNGCEs have been applied
      to determine the concentration of dopamine to be 0.59 +/- 0.07 MUM in PC12 cells.

PMID- 22483357
TI  - Enantioselective and label-free detection of oligopeptide via fluorescent
      indicator displacement.
AB  - In this work, a simple and label-free fluorescent method via fluorescent
      indicator displacement (FID) was proposed for enantioselectively determining d
      enantiomer of arginine vasopressin (DV) using DV-specific DNA aptamer (V-apt) and
      one guanidiniophthalocyanine dye (Zn-DIGP). Zn-DIGP that preferentially binds to
      single-stranded DNA with fluorescence enhancement rather than duplexes occupies
      the long internal loop of V-apt and generates intensive fluorescence. Then DV is
      introduced into the solution containing Zn-DIGP and V-apt, and displaces the Zn
      DIGP from the binding site of internal loop, leading to fluorescence decrease.
      But l-enantiomer cannot induce any fluorescence change due to the selectivity of
      V-apt. This established FID technique can detect DV with a detection limit of 100
      nM and exhibits a broad linear range, and is able to discriminate enantiomers of
      arginine vasopressin unambiguously. Moreover chiral separation by chromatography,
      complicated experimental procedures and covalent modification of tags (such as
      organic dyes, redox-active metal complexes) are avoided in our strategy. This
      simple and label-free method is promising for fabricating diverse aptasensors to
      determine other biomolecules and drugs.

PMID- 22483358
TI  - A host-guest-recognition-based electrochemical aptasensor for thrombin detection.
AB  - A sensitive electrochemical aptasensor for thrombin detection is presented based
      on the host-guest recognition technique. In this sensing protocol, a 15 based
      thrombin aptamer (ab. TBA) was dually labeled with a thiol at its 3' end and a 4
      ((4-(dimethylamino)phenyl)azo) benzoic acid (dabcyl) at its 5' end, respectively,
      which was previously immobilized on one Au electrode surface by AuS bond and used
      as the thrombin probe during the protein sensing procedure. One special
      electrochemical marker was prepared by modifying CdS nanoparticle with beta
      cyclodextrins (ab. CdS-CDs), which employed as electrochemical signal provider
      and would conjunct with the thrombin probe modified electrode through the host
      guest recognition of CDs to dabcyl. In the absence of thrombin, the probe adopted
      linear structure to conjunct with CdS-CDs. In present of thrombin, the TBA bond
      with thrombin and transformed into its special G-quarter structure, which forced
      CdS-CDs into the solution. Therefore, the target-TBA binding event can be
      sensitively transduced via detecting the electrochemical oxidation current signal
      of Cd of CdS nanoparticles in the solution. Using this method, as low as 4.6 pM
      thrombin had been detected.

PMID- 22483360
TI  - Assessment Battery for Communication: development of two equivalent forms.
AB  - The aim of this paper was to develop and test two equivalent forms of the
      Assessment Battery for Communication (ABaCo), a tool for evaluating pragmatic
      abilities in patients with neuropsychological and psychiatric disorders. The
      equivalent forms were created using the data from a sample of 390 children, then
      tested in a sample of 30 patients with traumatic brain injury. Equivalent forms
      of the same test are useful in clinical practice and intervention research, when
      performance needs to be tested on two separate occasions, for example before and
      after a rehabilitation program. The present results provide additional evidence
      on the psychometric functioning of the equivalent forms of the ABaCo and their
      usability in a clinical context. LEARNING OUTCOMES: The reader will be able to
      discuss the evidence of the psychometric propriety of the equivalent forms of the
      ABaCo and describe its potential usefulness.

PMID- 22483359
TI  - Immunotherapy: a useful strategy to help combat multidrug resistance.
AB  - Multidrug resistance (MDR) renders cancer cells relatively invulnerable to
      treatment with many standard cytotoxic anti-cancer agents. Cancer immunotherapy
      could be an important adjunct for other strategies to treat MDR positive cancers,
      as resistance to immunotherapy generally is unrelated to mechanisms of resistance
      to cytotoxic agents. Immunotherapy to combat MDR positive tumors could use any of
      the following strategies: direct immune attack against MDR positive cells, using
      MDR as an immune target to deliver cytotoxic agents, capitalization on other
      immune properties of MDR positive cells, or conditional immunotoxins expressed
      under MDR control. Additional insights into the immunogenic potential of some
      cytotoxic agents can also be brought to bear on these strategies. This review
      will highlight key concepts in cancer immunotherapy and illustrate immune
      principles and strategies that have been or could be used to help destroy MDR
      positive tumor cells, either alone or in rational combinations.

PMID- 22483361
TI  - Functional brain imaging of appetite.
AB  - Obesity is a neurobehavioral disorder that results from a combination of
      overeating and insufficient physical activity. Finely tuned mechanisms exist to
      match food intake to caloric expenditure. However, faced with abundant
      inexpensive and calorie-dense foods, many humans (and perhaps most) have a
      tendency to consume beyond their caloric needs. The brain controls food intake by
      sensing internal energy-balance signals and external cues of food availability,
      and by controlling feeding behavior; it is therefore at the centre of the obesity
      problem. This article reviews the recent use of functional brain imaging in
      humans to study the neural control of appetite, and how the neural systems
      involved may cause vulnerability to overeating in the obesogenic environment.

PMID- 22483362
TI  - Let's prevent peer victimization, not just bullying.

PMID- 22483363
TI  - Transactional sex as a form of child sexual exploitation and abuse in Rwanda:
      implications for child security and protection.
AB  - OBJECTIVE: To illuminate the different manifestations of transactional sexual
      exploitation and abuse among Rwanda's children in order to inform effective
      responses by policies, programs, and communities. METHOD: Qualitative data was
      collected during April and May 2010. One-hundred and thirty-nine adults (56%
      female) and 52 children (60% female) participated in focus groups across three
      geographic locations in Rwanda. Eleven interviews were held with child protection
      stakeholders. RESULTS: Interview and focus group participants reported how
      children, primarily girls, engaged in transactional sex as a survival strategy in
      response to situations of adversity including economic deprivation, difficulty
      accessing school, and social pressure. CONCLUSIONS: Policy and programs should
      work to address the underlying social and economic determinants of transactional
      sexual exploitation through structural interventions that reduce gender
      inequalities to accessing school and securing basic needs. Further quantitative
      and qualitative research to better understand the complexities of this issue is
      warranted.

PMID- 22483364
TI  - Fish oil improves the lipid profile and reduces inflammatory cytokines in Wistar
      rats with precancerous colon lesions.
AB  - A fatty diet is regarded as one of the most important risk factors related to the
      etiology of colorectal cancer, and this effect is linked to the quantity and
      principal types of fatty acids consumed. In this study, the chemopreventive
      effects of different oils on rats were investigated. Forty Wistar rats received
      1,2-dimetilhidrazine (DMH) and were divided into 4 groups fed normal lipid diets
      to which 4% olive, fish, flaxseed, or soybean oils (control) were added. The
      group fed with fish oil presented higher levels of eicosapentaenoic acid (EPA)
      and docosahexaenoic acid in hepatic tissue and greater levels of linolenic acid
      and EPA in adipose tissue compared to the other treatments. In the proximal
      portion of the colon, lower levels of aberrant crypt foci were found in the fish
      and flaxseed oil groups; however, this behavior was not observed in the middle
      and distal regions. Via a benchmarking method, the fish oil group showed a
      greater transforming growth factor beta expression and lower interleukin-8
      expression in relation to the other treatments. Fish oil in a normal lipid diet
      demonstrated a limited protective effect on the colonic precancerous mucosa in
      carcinogen-treated rodents, whereas it had a beneficial effect on inflammatory
      modulation.

PMID- 22483365
TI  - Kinetic modeling of Pt-catalyzed glycolaldehyde decomposition to syngas.
AB  - Fundamental knowledge of the elementary reaction mechanisms involved in oxygenate
      decomposition on transition metal catalysts can facilitate the optimization of
      future catalyst and reactor systems for biomass upgrade to fuels and chemicals.
      Pt-catalyzed decomposition of glycolaldehyde, as the smallest oxygenate with
      alcohol and aldehyde functionality, was studied via a DFT-based microkinetic
      model. It was found that two decomposition pathways exist. Under conditions of
      low hydrogen surface coverage, the initial C-H bond breaking reaction to
      HOCH(2)CO* is prevalent, while under conditions of high hydrogen coverage, the
      rather unexpected O-H bond forming reaction to HOCH(2)CHOH* is more active
      (subsequent decomposition is energetically favorable from HOCH(2)CHOH*). Our
      results indicate the possibility that (de)hydrogenation chemistry is rate
      controlling in many small polyoxygenate biomass derivatives, and suitable
      catalysts are needed. Finally, DFT was used to understand the increased
      decomposition activity observed on the surface segregated Ni-Pt-Pt bimetallic
      catalyst. It was found that the initial O-H bond breaking of glycolaldehyde to
      OCH(2)CHO* has an activation barrier of just 0.21 eV. This barrier is lower than
      that of any glycolaldehyde consuming reaction on Pt. These computational
      predictions are in qualitative agreement with experimental results.

PMID- 22483366
TI  - The relation of substance use with different levels of depressive symptoms and
      the moderating effect of sex and age in Taiwanese adolescents.
AB  - BACKGROUND: The aim of this cross-sectional study was to examine (a) the relation
      of substance use with different levels of depressive symptoms and (b) the
      moderating effect of sex and age on the association between different levels of
      depressive symptoms and substance use in Taiwanese adolescents. METHODS: The
      study group consisted of 9070 adolescent students in southern Taiwan aged 12 to
      19 years who were sorted into 3 different levels of depressive symptoms on the
      Center for Epidemiologic Studies Depression Scale. The Questionnaire for
      Experience in Substance Use was used to assess each participant's experience with
      smoking, alcohol consumption, betel nut chewing, sedative/hypnotic use, and
      illicit drug use in the preceding year. The rates of substance use were compared
      among adolescents with different levels of depressive symptoms using generalized
      linear mixed-model analysis. The moderating effects of sex and age on the
      association between different levels of depressive symptoms and substance use
      were also examined. RESULTS: Adolescents with severe depressive symptoms had
      higher rates of using all 5 kinds of substances than did nondepressed ones.
      Adolescents with minor depressive symptoms had higher rates of using all
      substances except for illicit drugs than did nondepressed ones. There was no
      significant difference in the rates of substance use between adolescents with
      severe and minor depressive symptoms. Sex and age had no moderating effect on the
      association between the level of depressive symptoms and substance use.
      CONCLUSIONS: It is necessary to carefully screen substance use among adolescents
      with depressive symptoms, even if they are below the threshold for significant
      depression.

PMID- 22483367
TI  - A meta-analysis of the association between posttraumatic stress disorder and
      suicidality: the role of comorbid depression.
AB  - OBJECTIVE: A considerable number of studies have reported an increased frequency
      of suicidal behaviors among individuals diagnosed with posttraumatic stress
      disorder (PTSD). This study aims, first, to provide a comprehensive systematic
      review and meta-analysis of the association between a PTSD diagnosis and
      frequency of suicidality and, second, to examine the role of comorbid depression
      in the association between suicidality and PTSD. METHODS: Searches of Medline
      (June 2010), EMBASE (June 2010), PsycINFO (June 2010), PILOTS (June 2010), and
      Web of Science (June 2010) were conducted to identify studies that examined the
      association between PTSD and suicidality. The studies had to include an effect
      size of the association between PTSD and suicidality to be included in the meta
      analysis. Sixty-three studies were eligible for inclusion in the meta-analysis.
      Overall and subgroup effect sizes were examined. RESULTS: A highly significant
      positive association between a PTSD diagnosis and suicidality was found. The PTSD
      suicidality association persisted across studies using different measures of
      suicidality, current and lifetime PTSD, psychiatric and nonpsychiatric samples,
      and PTSD populations exposed to different types of traumas. Comorbid major
      depression significantly compounded the risk for suicide in PTSD populations.
      CONCLUSION: The current meta-analysis provides strong evidence that a PTSD
      diagnosis is associated with increased suicidality. The crucial role of comorbid
      major depression in the etiology of suicidality in PTSD is also supported.

PMID- 22483369
TI  - Green Net Regional Product for the San Luis Basin, Colorado: an economic measure
      of regional sustainability.
AB  - This paper presents the data sources and methodology used to estimate Green Net
      Regional Product (GNRP), a green accounting approach, for the San Luis Basin
      (SLB). We measured the movement away from sustainability by examining the change
      in GNRP over time. Any attempt at green accounting requires both economic and
      natural capital data. However, limited data for the Basin requires a number of
      simplifying assumptions and requires transforming economic data at the national,
      state, and county levels to the level of the SLB. Given the contribution of
      agribusiness to the SLB, we included the depletion of both groundwater and soil
      as components in the depreciation of natural capital. We also captured the effect
      of the consumption of energy on climate change for future generations through
      carbon dioxide (CO(2)) emissions. In order to estimate the depreciation of
      natural capital, the shadow price of water for agriculture, the economic damages
      from soil erosion due to wind, and the social cost of carbon emissions were
      obtained from the literature and applied to the SLB using benefit transfer. We
      used Colorado's total factor productivity for agriculture to estimate the value
      of time (i.e., to include the effects of exogenous technological progress). We
      aggregated the economic data and the depreciation of natural capital for the SLB
      from 1980 to 2005. The results suggest that GNRP had a slight upward trend
      through most of this time period, despite temporary negative trends, the longest
      of which occurred during the period 1985-86 to 1987-88. However, given the upward
      trend in GNRP and the possibility of business cycles causing the temporary
      declines, there is no definitive evidence of moving away from sustainability.

PMID- 22483368
TI  - Metabolic syndrome in obese men and women with binge eating disorder:
      developmental trajectories of eating and weight-related behaviors.
AB  - Metabolic syndrome (MetSyn), characterized by vascular symptoms, is strongly
      correlated with obesity, weight-related medical diseases, and mortality and has
      increased commensurately with secular increases in obesity in the United States.
      Little is known about the distribution of MetSyn in obese patients with binge
      eating disorder (BED) or its associations with different developmental
      trajectories of dieting, binge eating, and obesity problems. Furthermore,
      inconsistencies in the limited data necessitate elucidation. This study examined
      the frequency and correlates of MetSyn in a consecutive series of 148 treatment
      seeking obese men and women with BED assessed with structured clinical
      interviews. Almost half of the participants met the criteria for MetSyn.
      Participants with MetSyn did not differ from those without MetSyn on demographic
      variables or disordered eating psychopathology. However, our findings suggest
      that MetSyn is associated with a distinct developmental trajectory, specifically
      a later age at BED onset and shorter BED duration. Although the findings from
      this study shed some light on MetSyn and its associations with developmental
      trajectories of eating and weight-related behaviors, notable inconsistencies
      characterize the limited literature. Prospective studies are needed to examine
      causal connections in the development of the MetSyn in relation to disordered
      eating in addition to excess weight.

PMID- 22483371
TI  - The effect of ballroom dance on balance and functional autonomy among the
      isolated elderly.
AB  - The aim of the present study was to analyze the influence of a ballroom dancing
      program on the functional autonomy and physical balance of institutionalized
      elderly individuals. The study enrolled 75 sedentary elderly subjects from long
      term institutions who were randomly divided into a ballroom dance program group
      (EG; n=39) and a control group (CG; n=36). The protocol of the Latin American
      Group for Maturity (GDLAM) was used to evaluate functional autonomy. Physical
      balance was analyzed using a stabilometer and posture meter platforms. The level
      of significance in statistical tests was set at p<0.05. Regarding the physical
      balance evaluation, only the members of the EG achieved a significant reduction
      in weight (Delta=-0.98 kg) following the experiment, both in the intragroup
      (p=0.002) and in the intergroup analysis (p=0.012). In the evaluation of
      functional autonomy, only the EG showed a significant reduction in the execution
      time of all the tests and in the GDLAM index: GI (Delta=-6.99), both in the
      intragroup (p<0.001) and in the intergroup analysis (p=0.011). Thus, it can be
      inferred that sedentary elderly individuals who are residents of long-term
      institutions can improve their functional autonomy and balance with a ballroom
      dance program.

PMID- 22483372
TI  - A prospective, randomized, double-blinded comparison between multimodal thoracic
      paravertebral bupivacaine and levobupivacaine analgesia in patients undergoing
      lung surgery.
AB  - OBJECTIVES: To compare the effects of paravertebral analgesia with
      levobupivacaine or bupivacaine on intra- and postoperative pain for thoracic
      surgery. DESIGN: A prospective, randomized, and double-blinded study. SETTING: A
      university hospital. PARTICIPANTS: Forty patients undergoing thoracic surgery.
      INTERVENTIONS: Patients received paravertebral catheterization and a bolus (14-20
      mL) of 0.5% bupivacaine (n = 20) or 0.5% levobupivacaine (n = 20) with morphine,
      60 MUg/kg, before the induction of general anesthesia that consisted of a
      propofol infusion. A paravertebral continuous infusion (0.05 mL/kg/h) of 0.25%
      bupivacaine or 0.25% levobupivacaine, 100 mL, with added morphine, 10 mg, and
      clonidine, 0.15 mg, was started at the end of surgery for 72 hours
      postoperatively. Postoperative rescue diclofenac analgesia was available if
      required. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intraoperative
      fentanyl consumption. Static and dynamic pain scores measured by a visual analog
      scale were assessed regularly. Intraoperative fentanyl consumption was
      significantly lower in the levobupivacaine group compared with the bupivacaine
      group (p = 0.001). On all 3 postoperative days, static pain scores were
      significantly lower in the levobupivacaine group compared with the bupivacaine
      group (p < 0.05). Dynamic pain scores were significantly lower in the
      levobupivacaine group compared with the bupivacaine group during the 2
      postoperative days (p < 0.05). A smaller proportion of patients in the
      levobupivacaine group used rescue analgesia (p < 0.005). CONCLUSIONS:
      Paravertebral analgesia with levobupivacaine resulted in less intraoperative
      fentanyl consumption, lower static (3 days) and dynamic (2 days) pain scores, and
      less rescue analgesia than analgesia with bupivacaine.

PMID- 22483373
TI  - Fuzzy clustering in Intelligent Scissors.
AB  - In this study a modified Live-Wire approach is presented. A Fuzzy C-Means (FCM)
      clustering procedure has been implemented before the wavelet transform cost map
      function is defined. This shrinks the area to be searched resulting in a
      significant reduction of the computational complexity. The method has been
      employed to computed tomography (CT) and magnetic resonance (MR) studies. The 2D
      segmentation of lungs, abdominal structures and knee joint has been performed in
      order to evaluate the method. Significant numerical complexity reduction of the
      Live-Wire algorithm as well as improvement of the object delineation with a
      decreased number of user interactions have been obtained.

PMID- 22483374
TI  - Community-based programs for children and youth: our experiences in design,
      implementation, and evaluation.

PMID- 22483375
TI  - Meniscus transplantation using treated xenogeneic meniscal tissue: viability and
      chondroprotection study in rabbits.
AB  - PURPOSE: This was a preliminary study performed in vivo to evaluate the viability
      and the chondroprotective effects of irradiated deep-frozen xenogeneic meniscal
      tissue as a novel substitute for meniscus transplantation. METHODS: Medial
      meniscectomies were performed on the right knees of 48 New Zealand white rabbits.
      The inner one-third of pig meniscus was harvested and then irradiated and deeply
      frozen. The treated xenogeneic meniscal tissues were then transplanted to 24
      right knees (Xeno group), whereas 24 other knees received meniscus allograft
      transplantations (Allo group). The left knees of the Xeno group and Allo group
      received meniscectomies (Meni group) and sham operations (Sham group),
      respectively. The rabbits were killed at weeks 6, 12, and 24 postoperatively. The
      newly formed structure of the implanted tissue and cartilage of the medial
      compartment of each group was assessed by gross and semiquantitative histologic
      analysis. RESULTS: After 24 weeks, the implanted xenogeneic meniscal tissue
      completely healed to the synovium and formed meniscus-like tissue. The
      chondrocyte-like cell infiltrated into the tissue with extracellular matrix
      including type II collagen and proteoglycans. The Xeno group showed significantly
      less cartilage degeneration than that of the Meni group in the medial tibial
      plateau at week 24 (P < .05). No significant difference was found between the
      Xeno group and the Allo group except for the meniscus-covered regions at week 24.
      From week 12 to week 24, almost no advanced cartilage degeneration was found in
      weight-bearing regions of the medial tibial plateau of the Xeno group.
      CONCLUSIONS: The treated xenogeneic meniscal tissue healed to the synovium with
      tissue regeneration and slowed down articular cartilage degeneration in the short
      term. The chondroprotection of xenograft transplantation was similar to that of
      allograft transplantation. CLINICAL RELEVANCE: The treated xenogeneic meniscal
      tissue showed the potential for viability and slowed cartilage degeneration, but
      more studies are required for application in humans in the future.

PMID- 22483376
TI  - The origins of the trypanosome genome strains Trypanosoma brucei brucei TREU 927,
      T. b. gambiense DAL 972, T. vivax Y486 and T. congolense IL3000.
AB  - The genomes of several tsetse-transmitted African trypanosomes (Trypanosoma
      brucei brucei, T. b. gambiense, T. vivax, T. congolense) have been sequenced and
      are available to search online. The trypanosome strains chosen for the genome
      sequencing projects were selected because they had been well characterised in the
      laboratory, but all were isolated several decades ago. The purpose of this short
      review is to provide some background information on the origins and biological
      characterisation of these strains as a source of reference for future users of
      the genome data. With high throughput sequencing of many more trypanosome genomes
      in prospect, it is important to understand the phylogenetic relationships of the
      genome strains.

PMID- 22483377
TI  - Levels of angiopoietins 1 and 2 in induced sputum supernatant in patients with
      COPD.
AB  - Pathological features of chronic obstructive pulmonary disease (COPD) include
      lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an
      essential mediator of angiogenesis by establishing vascular integrity, whereas
      angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of
      angiopoietins in sputum supernatants of patients with COPD and investigated their
      possible association with mediators and cells involved in the inflammatory and
      remodeling process. Fifty-nine patients with COPD, 25 healthy smokers and 20
      healthy non-smokers were studied. All subjects underwent lung function tests,
      sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-beta1,
      MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular
      permeability (AVP) index was also assessed. Ang-2 levels were significantly
      higher in patients with COPD compared to healthy smokers and healthy non-smokers
      [median, interquartile ranges pg/ml, 267 (147-367) vs. 112 (67-171) and 98 (95
      107), respectively; p<0.001]. Regression analysis showed a significant
      association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in
      COPD, the strongest being with VEGF. Our results indicate that induced sputum Ang
      2 levels are higher in COPD compared to healthy smokers and healthy non-smokers.
      Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a
      possible role for Ang-2 in the pathogenesis of the disease.

PMID- 22483378
TI  - Fragile X syndrome: mechanistic insights and therapeutic avenues regarding the
      role of potassium channels.
AB  - Fragile X syndrome (FXS) is a common form of mental disability and one of the
      known causes of autism. The mutation responsible for FXS is a large expansion of
      the trinucleotide CGG repeats that leads to DNA methylation of the fragile X
      mental retardation gene 1 (FMR1) and transcriptional silencing, resulting in the
      absence of fragile X mental retardation protein (FMRP), an mRNA binding protein.
      Although it is widely known that FMRP is critical for metabotropic glutamate
      receptor (mGluR)-dependent long-term depression (LTD), which has provided a
      general theme for developing pharmacological drugs for FXS, specific downstream
      targets of FMRP may also be of therapeutic value. Since alterations in potassium
      channel expression level or activity could underlie neuronal network defects in
      FXS, here we describe recent findings on how these channels might be altered in
      mouse models of FXS and the possible therapeutic avenues for treating FXS.

PMID- 22483379
TI  - Feline vaccination practices and protocols used by veterinarians in the United
      Kingdom.
AB  - Vaccination is an important aspect of disease control in the feline population,
      as it prevents disease or reduces its severity in individual cats. However the
      types of antigens that should be administered to cats, the frequency of
      administration of certain antigens and the anatomical location at which vaccines
      should be administered are controversial. Various groups have developed
      guidelines to help veterinarians decide vaccine protocols for cats in their care.
      The aim of this study was to survey veterinarians in the United Kingdom about the
      vaccination protocols used in 2007-2008. A questionnaire about aspects of feline
      vaccination was distributed to a 431 veterinary practices taking part in a case
      control study of feline injection site sarcomas. A response rate of 72% was
      achieved. The majority of veterinarians who responded administered the commonly
      used antigens annually (84-96% of practices). Most of the veterinarians
      administered most vaccines in the interscapular region (90-96% of practices
      depending on the antigen). The vaccination practices of the veterinarians were
      not consistent with the published vaccination guidelines at that time.

PMID- 22483380
TI  - Mucosal imbalance of interleukin-1beta and interleukin-1 receptor antagonist in
      canine inflammatory bowel disease.
AB  - Interleukin (IL)-1beta is a key mediator of the inflammatory response. IL-1
      receptor antagonist (IL-1Ra) regulates inflammation by functioning as an
      endogenous inhibitor of IL-1beta. A disruption of the balance between IL-1beta
      and IL-1Ra has been identified in human inflammatory bowel disease (IBD). The
      objective of this study was to determine whether there is an intestinal imbalance
      of IL-1beta and IL-1Ra in canine IBD by comparing expression of IL-1beta and IL
      1Ra mRNA by real-time RT-PCR and expression of IL-1beta and IL-1Ra protein by
      ELISA in 21 dogs with IBD, 15 dogs with intestinal lymphoma ('inflammatory'
      controls) and 20 healthy Beagles ('healthy' controls). A significant decrease in
      the intestinal IL-1Ra:IL-1beta ratio of mRNA and protein was observed in IBD
      cases when compared with healthy control dogs. In contrast, a decrease in IL
      1Ra:IL-1beta ratio was not observed in dogs with intestinal lymphoma. The IL
      1Ra:IL-1beta protein ratio was negatively correlated with clinical severity in
      dogs with IBD. An intestinal imbalance between IL-1beta and IL-1Ra production may
      play a role in the pathogenesis of canine IBD.

PMID- 22483381
TI  - Well-differentiated gastric carcinoids treated with somatostatin analogues.

PMID- 22483382
TI  - Salmonellosis in cattle: advantages of being an experimental model.
AB  - Salmonellosis is an important disease of cattle caused predominantly by
      Salmonella enterica serotypes Typhimurium (S. typhimurium) and Dublin (S.
      dublin). S. typhimurium causes acute enteritis and exudative diarrhea in calves.
      In addition to enteric disease, S. dublin can cause systemic infections, and may
      cause abortion in pregnant cows. Calves are considered a relevant model for non
      typhoidal salmonellosis in humans. Experimental oral infections or inoculation of
      ligated ileal loops in calves have been extensively studied recently. This
      article reviews relevant published results regarding bovine salmonellosis as a
      natural disease or as an animal model.

PMID- 22483383
TI  - Photoacoustic investigation of maghemite-based nanocomposite.
AB  - Photoacoustic spectroscopy was used to investigate magnetic nanocomposites
      incorporating nanosized maghemite particles into styrene-divinylbenzene copolymer
      template. Typical photoacoustic features were observed in bands C, S and L in the
      wavelength region of 300-1000 nm. The relative intensity of band-C scaled with
      the nominal concentration of nanosized maghemite incorporated into the polymeric
      template whereas the lowest relative intensity of band-S was found in the sample
      in which the template polymerization took place in the presence of the highest
      polar-like reaction medium. X-ray diffraction and transmission electron
      microscopy were used to characterize the magnetic nanosized phase as maghemite,
      with average particle diameter of 6.9 nm (sample Est34), 7.0 nm (sample H30), and
      7.9 nm (sample Em15).

PMID- 22483384
TI  - Predictors of fluoroscopy time and procedural failure during biventricular device
      implantation.
AB  - Biventricular device implantation with the insertion of a transvenous left
      ventricular (LV) lead can be challenging. The aim of this study was to identify
      predictors of procedural difficulty measured by fluoroscopy time and predictors
      of LV lead implantation failure. A single-center, retrospective study of 272
      consecutive patients who underwent biventricular device implantation from 2004 to
      2011 was conducted. Multivariate linear regression was used to assess predictors
      of fluoroscopy time and logistic regression to identify predictors of LV lead
      implant failure. The median fluoroscopy time was 36.1 minutes (interquartile
      range 24.2 to 51.6). After multivariate adjustment, independent predictors of
      longer fluoroscopy time included a right-sided approach (21.8 minutes longer, 95%
      confidence interval [CI] 6.8 to 36.9, p = 0.005), previous congenital heart
      disease surgery (64.6 minutes longer, 95% CI 30.2 to 99.0, p <0.001), and
      previous failed attempt (30.3 minutes longer, 95% CI 6.0 to 54.5, p = 0.015).
      Predictors of shorter fluoroscopy time included an LV lead upgrade (7.5 minutes
      shorter, 95% CI 0.6 to 14.4, p = 0.033), electrophysiology fellow experience (5.4
      minutes shorter/year, 95% CI 0.1 to 10.7, p = 0.047), and attending physician
      experience (1.4 minutes shorter/year, 95% CI 0.01 to 2.9, p = 0.049). Failed
      implantation occurred in 8% of patients (22 of 272); inability to cannulate the
      coronary sinus and absent or atretic coronary sinus veins were the most common
      reasons (8 of 22 failed implants each). A previous failed attempt was the only
      significant predictor of LV lead implantation failure (odds ratio 33.5, 95% CI
      3.2 to 352.6, p = 0.003). In conclusion, 6 patient and operator characteristics
      predicted LV lead implantation difficulty measured by fluoroscopy time. LV lead
      implantation failed in 8% of cases, predicted only by a previous failed attempt.

PMID- 22483385
TI  - Relation between abdominal obesity, insulin resistance and left ventricular
      hypertrophy diagnosed by electrocardiogram and magnetic resonance imaging in
      hypertensive patients.
AB  - Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on
      electrocardiography (ECG-LVH) is a result of increased cardiac electrical
      activity or due to increased left ventricular mass (LVM) remains to be
      determined. The aims of the present study were to investigate the relation
      between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in
      patients with hypertension and to investigate the relation of insulin resistance
      (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow
      Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist
      circumference was used as a measure of abdominal obesity. Linear regression
      analysis revealed an inverse relation (adjusted beta = -0.02, 95% confidence
      interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage,
      indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There
      was a positive relation between waist circumference and MRI-LVM (beta = 0.49, 95%
      confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a
      worse metabolic profile than patients with the Sokolow-Lyon voltage criterion.
      The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist
      circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an
      inverse relation between waist circumference and ECG-LVH and a positive relation
      between waist circumference and MRI-LVM. This study indicates that obesity has a
      different relation to voltage criteria for LVH compared to anatomic criteria for
      LVH, supporting the hypothesis that IR decreases electrocardiographic voltages,
      despite an increase in MRI-LVM. The clinical implication is that especially in
      patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.

PMID- 22483386
TI  - Effect of renal transplantation for chronic renal disease on left ventricular
      mass.
AB  - Chronic kidney disease is associated with an increased left ventricular (LV)
      mass. Few data are available regarding the effect of renal transplantation on LV
      mass regression or the clinical factors associated with LV mass regression.
      Patients with >=1 year of chronic kidney disease followed by successful renal
      transplantation were identified. All patients underwent echocardiography >=6
      months before transplantation with repeat echocardiography >=1 year after
      transplantation. An experienced echocardiographer, who was unaware of the
      clinical data, performed all linear measurements in the parasternal long-axis
      projection, including systolic and diastolic LV chamber dimensions and LV wall
      thickness. The LV mass was calculated as follows: 0.8 * {1.04 [(LV internal
      dimension at end diastole + posterior wall thickness at end diastole + LV wall
      thickness at the cardiac base for the anteroseptum)(3) - (LV internal dimension
      at end diastole)(3)]} + 0.6 g. Candidate clinical variables for an association
      with LV mass regression were assembled, including age, gender, race, donor type,
      renal disease etiology, medications (insulin, oral hypoglycemics,
      antihypertensives, statins, and antirejection medications), and co-morbidities.
      Patients were separated into 2 groups according to presence and absence of LV
      mass regression. A total of 105 patients (mean age 54 years; 58 men) were
      included in the study with a mean follow-up of 1.7 years. Of the 105 patients, 57
      had significant LV mass regression (mean difference -37.2 +/- 31.3 g/m(2)) and 48
      had no significant regression (mean difference 15.7 +/- 17.1 g/m(2)). The extent
      of the LV mass before transplantation was the only predictor of mass regression
      after transplantation (odds ratio 1.50, 95% confidence interval 1.26 to 1.80). In
      conclusion, significant LV mass regression is present in most patients after
      renal transplantation. The extent of the LV mass before transplantation was the
      only clinical predictor of regression.

PMID- 22483387
TI  - Pilot candidate gene analysis of patients >= 60 years old with aortic stenosis
      involving a tricuspid aortic valve.
AB  - The potential genetic basis of aortic stenosis in older people is poorly
      understood. A total of 265 patients with aortic stenosis involving tricuspid
      aortic valves and 961 controls were genotyped for <=660 candidate single
      nucleotide polymorphisms (SNPs). After dividing the patients and controls into
      training and validation sets, we tested the correlation of the SNPs with the age
      adjusted aortic valve area, determined by echocardiography or cardiac
      catheterization. A bootstrapped global p value of <=0.005 was considered evidence
      of a possible significant correlation. The cases were aged 73 +/- 7 years, and
      72.7% were men. The median aortic valve area was 1.0 cm(2) (interquartile range
      0.7 to 1.5). The controls were aged 69 +/- 6 years, and 69.8% were men. The minor
      allele frequency was 21% +/- 15% (37% <0.20). Three SNPs met the criteria for
      significant correlation (rs2276288 [MYO7A], p = 0.001; rs5194 [AGTR1], p = 0.004;
      rs207 307 [ELN], p = 0.005). Another 2 SNPs reached borderline significance (p
      <=0.008). In conclusion, we report 3 SNPs to be associated with aortic stenosis
      involving tricuspid aortic valves in older subjects. Given the concerns regarding
      the problem of multiple statistical testing, validation studies are required to
      further assess these correlations.

PMID- 22483388
TI  - On the calculations of interaction energies and induced electric properties
      within the polarizable continuum model.
AB  - In this work we investigate the influence of a polarizable environment on the
      interaction energies and the interaction-induced (excess) static electric dipole
      properties for the selected model hydrogen-bonded complexes. The excess
      properties were estimated for water and hydrogen fluoride dimers using the
      supermolecular approach and assuming the polarizable continuum model (PCM) as a
      representation of the polarizable environment. We analyze in this context the
      performance of the counterpoise correction and the consequences of various
      possible monomer cavity choices. The polarizable environment reduces the absolute
      magnitudes of interaction energies and interaction-induced dipole moments,
      whereas an increase is observed for the absolute magnitudes of induced
      polarizabilities and first hyperpolarizabilities. Our results indicate that the
      use of either monomeric (MC) or dimeric (DC) cavities in calculations of monomer
      properties does not change qualitatively the resultant excess properties. We
      conclude that the DC scheme is more consistent with the definition of the
      interaction energy and consequently also the interaction-induced property,
      whereas the MC scheme corresponds to the definition of stabilization energy. Our
      results indicate also a good performance of the counterpoise correction scheme
      for the self-consistent methods in the case of all studied properties.

PMID- 22483389
TI  - Dimerization of beta-tryptase inhibitors, does it work for both basic and neutral
      P1 groups?
AB  - The tetrameric folding of beta-tryptase and the pair-wise distribution of its
      substrate binding sites offer a unique opportunity for development of inhibitors
      that span two adjacent binding sites. A series of dimeric inhibitors with two
      basic P1 moieties was discovered using this design strategy and exhibited tight
      binder characteristics. Using the same strategy, an attempt was made to design
      and synthesize dimeric inhibitors with two neutral-P1 groups in hope to exploit
      the dimeric binding mode to achieve a starting point for further optimization.
      The unsuccessful attempt, however, demonstrated the important role played by
      Ala190 in neutral-P1 binding and casted further doubt on the possibility of
      developing neutral-P1 inhibitors for beta-tryptase.

PMID- 22483390
TI  - An approach for differentiating isozymes. Construction of libraries containing
      short aromatic peptides as part of a method to design selective inhibitors
      against lipases.
AB  - Through synthesis and assays of peptidyl substrates, we could select substrates
      having peptidyl complementary against lipases. The best substrate showed 20-fold
      improved K(m) relative to non-peptidyl substrate. Using this information, we
      generated selective inhibitors. Lipase activities with peptidyl substrates were
      represented as fingerprints. Differences in fingerprints reflect different
      structures near active site of lipases, could be used for generating selective
      inhibitors.

PMID- 22483391
TI  - 3D-QSAR Study on dihydro-1,3,5-triazines and their spiro derivatives as DHFR
      inhibitors by comparative molecular field analysis (CoMFA).
AB  - A 3D-QSAR/CoMFA was performed for a series of triazine and its spiro derivative
      based DHFR inhibitors displaying IC(50) values ranging from 0.002 to 58.8 MUM.
      Analyses resulted in a reliable computational model with the parameters of n=46,
      r(2)=0.986, q(2)=0.724, SE=0.164, F=275.889. It is shown that the steric and
      electrostatic properties predicted by CoMFA contours can be related to the DHFR
      inhibitory activity. The predictive ability of the resultant model was evaluated
      using a test set comprised of 18 molecules and the results show that the CoMFA
      model is able to correctly predict the poor inhibitory activities of the
      compounds in the testing set. This model is a significant guide to trace the
      features that really matter especially with respect to the design of novel
      compounds.

PMID- 22483392
TI  - Synthesis, characterization, molecular docking and cytotoxic activity of novel
      plumbagin hydrazones against breast cancer cells.
AB  - Novel plumbagin hydrazonates were prepared, structurally characterized and
      evaluated for anti-proliferative activity against estrogen receptor-positive MCF
      7 and triple negative MDA-MB-231 and MDA-MB-468 breast cancer cell lines which
      exhibited superior inhibitory activity than parent plumbagin compound. Molecular
      docking studies indicated that hydroxyl groups on plumbagin and hydrazonate side
      chain favor additional hydrogen bonding interactions with amino acid residues in
      p50-subunit of NF-kappaB protein and these compounds inhibited NF-kappaB
      expression which may be responsible for the enhanced anti-proliferative activity.
      These compounds were found to be more effective against triple negative breast
      cancer cells and might serve as a starting point for building future strategies
      against triple negative breast cancers which are known for their increased drug
      resistance and poor prognosis of breast cancer patients.

PMID- 22483393
TI  - Synthesis and evaluation of anti-thrombotic activity of benzocoumarin amide
      derivatives.
AB  - A series of novel benzocoumarin amide derivatives have been synthesized and
      evaluated for their anti-thrombotic activity. Amongst these, compounds 5, 7 and 8
      exhibited promising anti-thrombotic profile in an established model of mouse
      thrombosis. Hence, comprehensive profiling on platelet aggregation and
      coagulation parameters was carried out to assess its potential as a lead
      candidate. In vitro treatment of these compounds in mice plasma resulted into
      significant reduction in ADP (p<0.01) and collagen (p<0.001) induced platelet
      aggregation. Moreover, Compounds 5, 7 and 8 also significantly increased thrombin
      time (p<0.05). Thus, in the present study, these benzocoumarin amide derivatives
      exhibited anti-thrombotic profile via both anti-platelet as well as anti
      coagulant action.

PMID- 22483394
TI  - Enzymatic synthesis of 8-vinyl- and 8-styryl-2'-deoxyguanosine modified DNA-
      novel fluorescent molecular probes.
AB  - Fluorescent analogs of the natural nucleobases are widely used as molecular
      probes for investigating DNA hybridization and topology. In this study the
      guanosine analogs 8-vinyl- and 8-styryl-2'-deoxyguanosine were synthesized and
      converted into the corresponding 5'-triphosphates. These C8 modified nucleotides
      were processed by various DNA polymerases to create fluorescent DNA. Whereas the
      8-styryl modified nucleotide somewhat hampers DNA synthesis 8-vinyl-2'
      deoxyguanosine is processed by DNA polymerases emphasizing the broad
      applicability as a molecular probe for fluorescence spectroscopy.

PMID- 22483395
TI  - Cytotoxic cytochalasins from the endozoic fungus Phoma sp. of the giant jellyfish
      Nemopilema nomurai.
AB  - Four new cytochalasin derivatives (1-4), together with cytochalasin B (5), were
      isolated from the fungus Phoma sp. obtained from the giant jellyfish Nemopilema
      nomurai. The planar structure and relative stereochemistry were established by
      analysis of 1D and 2D NMR data. The absolute configuration was defined by the
      modified Mosher's method. The compounds showed significant cytotoxicity against a
      small panel of human solid tumor cell lines (A549, SK-OV-3, SK-MEL-2, XF 498, and
      HCT15) with IC(50) values in the range of 0.5-30 MUM. The cytochalasin B (5)
      showed obvious cytotoxicity with IC(50) of 7.9 MUM against HeLa human cervical
      carcinoma cells.

PMID- 22483396
TI  - Rapid quantitative analysis of clarithromycin in rat plasma by UPLC-MS/MS after
      intravenous injection of the clarithromycin-loaded ultrafine PLGA nanoparticles.
AB  - Nanoparticles were designed to encapsulate drugs to alter their pharmacological
      behaviors, therefore, it is very essential to monitor the pharmacokinetic profile
      of drug encapsulated in nanoparticles in order to clarify and predict their
      efficacy and side effects. In this paper, we reported a simple, rapid MU-elution
      96-well solid phase extraction (MUSPE) method combining with ultra high
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for
      determination of nanoformulated drug in rat plasma. This method presented
      satisfactory results in terms of sensitivity, precision, accuracy, and recovery,
      for the first time, of quantitatively analyzing clarithromycin (CLA) in rat
      plasma after intravenous administration CLA-loaded ultrafine PLGA nanoparticles
      for pharmacokinetic study. This method has been proved to be fast, reliable and
      reproducible to accurately analyze drug encapsulated in polymeric nanoparticles
      sample for a pharmacokinetic study.

PMID- 22483397
TI  - High-sensitivity liquid chromatography-tandem mass spectrometry for the
      simultaneous determination of five drugs and their cytochrome P450-specific probe
      metabolites in human plasma.
AB  - A sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method
      with electrospray ionization was developed for the simultaneous quantitation of
      five probe drugs and their metabolites in human plasma for assessing the in vivo
      activities of cytochrome P450 (CYP). CYP isoform specific substrates and their
      metabolites of CYP1A2 (caffeine), CYP2C9 (losartan), CYP2C19 (omeprazole), CYP2D6
      (dextromethorphan) and CYP3A (midazolam) were all simultaneously analyzed using
      LC-MS/MS after administration of a mixture of five drugs (i.e., a "cocktail
      approach") to healthy volunteers. The assay uses propranolol as an internal
      standard; dual liquid extraction; a Xbridge MS C(18) (100 mm * 2.1mm, 3.5 MUm)
      column; a gradient mobile phase of 0.1% formic acid/acetonitrile (7/3->3/7); mass
      spectrometric detection in positive ion mode. The method was validated from 5 to
      500 ng/mL for caffeine and paraxanthine, 0.1-40 ng/mL for losartan and EXP3174,
      0.05-20 ng/mL for omeprazole and 5-hydroxyomeprazole, 0.008-0.8 ng/mL for
      dextromethorphan and dextrorphan, 0.01-1.0 ng/mL for midazolam, and 0.04-4 ng/mL
      for 1'-hydroxymidazolam. The intra- and inter-day precision over the
      concentration ranges for all analytes were lower than 12.5% and 13.8% (relative
      standard deviation, %RSD), and accuracy was between 86.5% and 108.4% and between
      87.0% and 107.0%, respectively. This highly sensitive and quantitative method
      allowed a pharmacokinetic study in subjects receiving doses 10-100 times lower
      than typical therapeutic doses.

PMID- 22483398
TI  - Validation of an on-line solid-phase extraction method coupled to liquid
      chromatography-tandem mass spectrometry detection for the determination of
      Indacaterol in human serum.
AB  - Indacaterol has been recently approved in Europe for the treatment of chronic
      obstructive pulmonary disease (COPD). In the present study, we have developed and
      validated a rapid and sensitive on-line solid phase extraction (SPE) method
      coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection
      for the determination of Indacaterol in human serum. The sample preparation
      involves the serum dilution with a 0.2% acetic acid solution prior to the on-line
      SPE on a mixed-mode cationic (MCX) polymer based sorbent. The samples were then
      eluted on a reversed phase column with a mobile phase made of acidified water and
      methanol and detection was performed by MS using electrospay ionization in
      positive mode. The analysis time between 2 samples was 7.0 min. Standard curves
      were linear over the range of 10.0 pg/mL (LLOQ) to 1000 pg/mL with correlation
      coefficient (r(2)) greater than 0.990. The method specificity was demonstrated in
      six different batches of human serum. Intra-run and inter-run precision and
      accuracy within +/- 20% (at the LLOQ) and +/- 15% (other levels) were achieved
      during a 3-run validation for quality control samples (QCs). The stability at
      room temperature (38 h) was determined and reported. In addition, the comparison
      between an off-line SPE procedure and our method gave equivalent results. The
      results of the present work demonstrated that our on-line SPE-LC-MS/MS method is
      rapid, sensitive, specific and could be applied to the quantitative analysis of
      Indacaterol in human serum samples. Our method effectively eliminated the tedious
      conditioning and rinsing steps associated with conventional off-line SPE and
      reduced the analysis time. The on-line SPE approach appears attractive for
      supporting the analysis of several hundreds of clinical samples.

PMID- 22483399
TI  - Typing of Lactobacillus sanfranciscensis isolates from traditional sourdoughs by
      combining conventional and multiplex RAPD-PCR profiles.
AB  - In the present work, a rapid and reproducible molecular method, based on the
      combination of conventional and multiplex RAPD-PCR reactions, was developed for
      typing Lactobacillus sanfranciscensis isolates from traditional sourdoughs. At
      first, four random primers, two used singly and two combined with the primer RD1,
      were chosen on the basis of their differentiating capability and reproducibility.
      The four resulting profiles for each isolate were integrated into a unique
      profile to be statistically treated by cluster analysis. The method was validated
      on 58 L. sanfranciscensis isolates coming from three traditional Italian
      sourdoughs. This new RAPD method was useful for determining the genomic diversity
      within the L. sanfranciscensis species. In particular, the intraspecific
      diversity of this species seemed to be related to the sourdough origin.

PMID- 22483400
TI  - Presence and survival of Escherichia coli O157:H7 on lettuce leaves and in soil
      treated with contaminated compost and irrigation water.
AB  - Escherichia coli O157:H7 outbreaks associated with produce consumption have
      brought attention to contaminated compost manure, and polluted irrigation water
      as potential sources of pathogens for the contamination of these crops. The aim
      of this study was to determine the potential transfer of E. coli O157:H7 from
      soil fertilized with contaminated compost or irrigated with contaminated water to
      edible parts of lettuce together with its persistence in soil under field
      conditions in two different seasons (fall and spring). Moreover, its survival on
      lettuce sprinkled with contaminated irrigation water was evaluated, as well as
      the prevalence of aerobic mesophilic, Enterobacteriaceae and Pseudomonadaceae in
      control lettuce samples. Four treatments, contaminated compost, surface and
      sprinkle irrigation with contaminated water and uninoculated pots, were used in
      this work. Contaminated compost was applied to soil in the pots before lettuce
      was transplanted and contaminated irrigation water was applied twice and three
      times on the plants after the seedlings were transplanted, for sprinkle and
      surface irrigation, respectively. E. coli O157:H7 survived in soil samples for 9
      weeks at levels, 4.50 log cfu gdw(-1) (dw, dry weight) in fall and 1.50 log cfu
      gdw(-1) in spring. The pathogen survives better in fall, indicating an important
      influence of environmental factors. E. coli O157:H7 population in lettuce leaves
      after sprinkle irrigation was very high (between 10(3) and 10(6) cfu g(-1)), but
      decreased to undetectable levels at field conditions. There was also transfer of
      E. coli O157:H7 from soil contaminated with compost or irrigated with
      contaminated water to lettuce leaves, mainly to the outer ones. The mean counts
      for aerobic mesophilic, Enterobacteriaceae and Pseudomonadaceae populations were
      also influenced by environmental conditions; higher levels were observed under
      fall conditions than in spring conditions. Contamination of lettuce plants in the
      field can occur through both contaminated composted manure and irrigation water
      and persist for several months.

PMID- 22483401
TI  - Characteristics of microbial biofilm on wooden vats ('gerles') in PDO Salers
      cheese.
AB  - The purpose of this study was to characterize microbial biofilms from 'gerles'
      (wooden vats for making PDO Salers cheese) and identify their role in milk
      inoculation and in preventing pathogen development. Gerles from ten farms
      producing PDO Salers cheese were subjected to microbial analysis during at least
      4 periods spread over two years. They were distinguished by their levels of
      Lactobacillus (between 4.50 and 6.01 log CFU/cm(2)), Gram negative bacteria
      (between 1.45 and 4.56 log CFU/cm(2)), yeasts (between 2.91 and 5.57 log
      CFU/cm(2)), and moulds (between 1.72 and 4.52 log CFU/cm(2)). They were then
      classed into 4 groups according their microbial characteristics. These 4 groups
      were characterized by different milk inoculations (with either sour whey or
      starter culture, daily or not), and different washing procedures (with water or
      whey from cheese making). The farm gerles were not contaminated by Salmonella,
      Listeria monocytogenes or Staphylococcus aureus. Only one slight, punctual
      contamination was found on one gerle among the ten studied. Even when the milk
      was deliberately contaminated with L. monocytogenes and S. aureus in the 40 L
      experimental gerles, these pathogens were found neither on the gerle surfaces nor
      in the cheeses. Using 40 L experimental gerles it was shown that the microbial
      biofilms on the gerle surfaces formed in less than one week and then remained
      stable. They were mainly composed of a great diversity of lactic acid bacteria
      (Leuconostoc pseudomesenteroides, Lactococcus lactis, Lactobacillus casei,
      Lactobacillus plantarum, Lactobacillus hilgardii,...), Gram positive catalase
      positive bacteria (Curtobacterium flaccumfaciens, Curtobacterium oceanosedimentum
      Citrococcus spp., Brachybacterium rhamnosum, Kocuria rhizophila, Arthrobacter
      spp....) and yeast (Kluyveromyces lactis, Kluyveromyces marxianus). In less than
      1 min, even in a 500 L farm gerle, the gerle's microbial biofilm can inoculate
      pasteurized milk with micro-organisms at levels superior to those in raw milk.

PMID- 22483402
TI  - Oomycetes, effectors, and all that jazz.
AB  - Plant pathogenic oomycetes secrete a diverse repertoire of effector proteins that
      modulate host innate immunity and enable parasitic infection. Understanding how
      effectors evolve, translocate and traffic inside host cells, and perturb host
      processes are major themes in the study of oomycete-plant interactions. The last
      year has seen important progress in the study of oomycete effectors with,
      notably, the elucidation of the 3D structures of five RXLR effectors, and novel
      insights into how cytoplasmic effectors subvert host cells. In this review, we
      discuss these and other recent advances and highlight the most important open
      questions in oomycete effector biology.

PMID- 22483403
TI  - Getting up to speed.

PMID- 22483404
TI  - Magnitude and management of hypercholesterolemia in the adult population of
      Spain, 2008-2010: The ENRICA Study.
AB  - INTRODUCTION AND OBJECTIVES: Only a few studies have reported nationwide
      population-based data on the magnitude and control of hypercholesterolemia. This
      work examines the prevalence and management of hypercholesterolemia in Spain.
      METHODS: Cross-sectional study conducted from June 2008 to October 2010 on 11,554
      individuals representative of the population aged >= 18 years in Spain. Study
      participants provided 12-h fasting blood samples, which were analyzed in a
      central laboratory with standardized methods. RESULTS: In the whole population,
      50.5% had hypercholesterolemia (total cholesterol >= 200 mg/dL or drug treatment)
      and 44.9% high levels of low-density lipoprotein cholesterol (>= 130 mg/dL or
      drug treatment), with no substantial sex-related differences. Moreover, 25.5% of
      men showed high-density lipoprotein cholesterol < 40 mg/dL and 26.4% of women
      high-density lipoprotein cholesterol <50mg/dL. Also, 23.2% of men and 11.7% of
      women had triglycerides >= 150 mg/dL. Frequency of dyslipidemia increased up to
      65 years, except for low high-density lipoprotein cholesterol which did not vary
      with age. Among those with high low-density lipoprotein cholesterol, 53.6% knew
      of it and 44.1% of them received lipid-lowering treatment; among the latter,
      55.7% had a controlled level (13.2% of all hypercholesterolemics). Control of
      high low-density lipoprotein cholesterol increased with age and with the number
      of visits to the specialist physician, but was lower among diabetics (odds
      ratio=0.38; 95% confidence interval, 0.28-0.53) and patients with cardiovascular
      disease (odds ratio=0.55; 95% confidence interval, 0.33-0.92). CONCLUSIONS: About
      half of the Spanish population has elevated serum cholesterol; moreover,
      cholesterol control is poor, particularly among those with highest cardiovascular
      risk, such as diabetics or patients with cardiovascular disease.

PMID- 22483405
TI  - Insights of modern pathology reports originating from prostate biopsy and radical
      prostatectomy specimens.

PMID- 22483407
TI  - Chronic kidney disease after nephrectomy in patients with small renal masses: a
      retrospective observational analysis.
AB  - CONTEXT: Chronic kidney disease (CKD) is a worldwide health threat associated
      with increased cardiovascular disease and mortality. OBJECTIVE: To examine
      postoperative CKD in patients with small renal masses (SRMs) treated with partial
      nephrectomy (PN) or radical nephrectomy (RN). DESIGN, SETTING, AND PARTICIPANTS:
      A US National Cancer Institute Surveillance Epidemiology and End Results (SEER)
      Medicare-linked retrospective cohort of 4633 T1aN0M0 renal cell carcinoma (RCC)
      patients who underwent PN or RN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      The primary outcome of interest was the onset of CKD stage >=3. Secondary end
      points comprised acute renal failure (ARF), chronic renal insufficiency (CRI),
      anemia in CKD, and end-stage renal disease (ESRD). Kaplan-Meier and Cox
      regression analyses were performed. RESULTS AND LIMITATIONS: Postpropensity
      matching resulted in 840 RN and PN patients. In multivariable analyses, RN
      patients were 1.9-, 1.4-, 1.8-, and 1.8-fold more likely to have an occurrence of
      CKD, ARF, CRI, and anemia in CKD, respectively (all p <= 0.004). The risk of ESRD
      between treatment groups failed to achieve statistical significance (p=0.06).
      CONCLUSIONS: PN is associated with more favorable postoperative renal function
      outcomes relative to RN in the setting of SRMs.

PMID- 22483408
TI  - [Semicircular lipoatrophy: are there effective alternative measures?].

PMID- 22483409
TI  - [Sexual behavior in adolescents aged 12 to 17 in Andalusia (Spain)].
AB  - OBJECTIVE: To describe sexual behavior and activity among adolescents aged 12-17
      years old in Andalusia (Spain) in 2007-2008. METHOD: The data for this study were
      collected through an anonymous questionnaire distributed to a stratified random
      sample of 2,225 secondary school students in Andalusia. Participation was
      voluntary. RESULTS: A total of 388 respondents (18.2%) reported having had
      complete sexual intercourse, with no statistically significant differences
      between boys (18.0%) and girls (18.5%). However, boys initiated the following
      practices earlier than girls: sexual activity (14 years versus 14.4 years),
      masturbation (11.3 years versus 12.7 years), oral sex (13.8 years versus 14.6
      years) and mutual masturbation (13.7 years versus 14.4 years). Other gender
      differences included the number of sexual partners (two in boys versus 1.6 in
      girls), recent sexual activity (higher in girls), internet sex (higher in boys),
      contraceptive use during the first coitus (lower in boys) and knowledge about
      double-barrier methods of contraception and sexually transmitted diseases (higher
      in girls). CONCLUSIONS: One out of six Andalusian secondary education students
      had had sexual intercourse. Two-thirds of the students were sexually active,
      especially girls, with limited knowledge of double-barrier methods and sexually
      transmitted diseases. The results of this study demonstrate the importance of
      including sex education as a core subject in the secondary education curriculum.

PMID- 22483410
TI  - Use of a donor heart with pre-transplant percutaneous patent foramen ovale
      closure.

PMID- 22483411
TI  - Fate of retained right ventricular assist device outflow grafts after right
      ventricular recovery.

PMID- 22483412
TI  - [Is there any indication for inserting a drain in elective laparoscopic
      cholecystectomy?].
AB  - INTRODUCTION: Classically, a sub-hepatic drain was inserted routinely in a
      cholecystectomy to prevent intra-abdominal abscesses, possible post-surgical
      bleeding, and biliary fistulas. Over the years, it has been demonstrated that the
      systematic use of a drain does not have any benefits, and many studies conclude
      that, in special circumstances (bleeding, signs of gallbladder inflammation,
      incidental opening, or suspected bile leak), and depending on the experience of
      the individual surgeon, the insertion of a drain may be of use. MATERIAL AND
      METHODS: [corrected] A prospective study was conducted on 100 elective
      laparoscopic cholecystectomies performed due to symptomatic cholelithiasis or
      gallbladder polyps. A sub-hepatic drain was inserted in 15 of them. The
      indications for inserting it were: in 11 patients as a "control" due to a
      gallbladder bed bleed controlled during surgery, and in 4 due to a gallbladder
      opening with the excretion of turbid-purulent bile. The main outcomes
      investigated were the clinical benefit achieved by the insertion of the drain,
      the hospital stay, and the quantifying of the pain by the patients 24h after
      surgery, using a visual analogue scale. RESULTS: The insertion of a drain was of
      no benefit to any patient. The median hospital stay increased by 1 day in
      patients with a drain (P=.002). The median pain score at 24h was higher in
      patients with a drain inserted (P=.018). CONCLUSION: The insertion of a sub
      hepatic drain after elective laparoscopic cholecystectomy increases post-surgical
      pain and prolongs hospital stay, and does not prevent the occurrence of intra
      abdominal abscesses.

PMID- 22483413
TI  - A higher rate of eating is associated with higher circulating interluekin-1beta
      concentrations in Japanese men not being treated for metabolic diseases.
AB  - OBJECTIVE: In this study, we examined the relations between the rate of eating
      and circulating interleukin (IL)-1beta and IL-6 levels in Japanese men not being
      treated for metabolic diseases. METHODS: We conducted a cross-sectional study of
      170 men 40 to 59 y old (mean +/- standard deviation, 51.4 +/- 5.7 y old) who
      participated in health checkups in Japan and were not being treated for metabolic
      diseases. We measured clinical serum parameters and plasma IL-1beta and IL-6
      concentrations and assessed by questionnaire lifestyle factors such as the
      dietary intake of food/nutrition and the rate of eating. Using multivariate
      linear regression analysis, we analyzed the relations between the rate of eating
      and IL-1beta and IL-6 concentrations, clinical parameters, and lifestyle factors.
      RESULTS: Significant Spearman correlation coefficients with the rate of eating
      were observed for IL-1beta and IL-6 (0.250 and 0.195, respectively). The rate of
      eating was positively associated with IL-1beta independently of IL-6, body mass
      index, homeostasis model assessment for insulin resistance, alcohol intake,
      energy intake, smoking status, and physical activity. CONCLUSIONS: These results
      indicate that a higher rate of eating is positively and independently associated
      with circulating IL-1beta concentrations in Japanese men not being treated for
      metabolic diseases.

PMID- 22483415
TI  - Characterization of two vasoactive peptides isolated from the plasma of the snake
      Crotalus durissus terrificus.
AB  - Incubation of plasma from the snake Crotalus durissus terrificus (CDTP) with
      trypsin generated two hypotensive peptides. The primary structure of the peptides
      was established for two sequences as: (Ser-Ile-Pro-Gln-Ala-Pro-Thr-Ser-Asn-Leu
      Ile-Glu-Ala-Thr-Lys) and (Lys-Pro-Asp-Ala-Asn-Gln-Val-Leu-Ile-Gln-Val-Ile-Gly
      Val). These peptides display homology with fragments of albumin from Trimeresurus
      flavoviridis. Bolus intra-arterial injection of the purified or the synthetic
      peptide produced a strong and sustained vasopressor response in the anaesthetized
      snake (CDT) and rats (Wistar); this hypotensive effect was also potentiated by
      captopril-an angiotensin-converting (0.1 mg/kg) enzyme inhibitor.

PMID- 22483414
TI  - Plasma ghrelin isoforms and gastric ghrelin O-acyltransferase expression are
      influenced by Helicobacter pylori status.
AB  - OBJECTIVE: Helicobacter pylori is known to affect the host's nutritional status.
      This study was performed to elucidate the relationship between H. pylori status
      and the dynamics of the ghrelin system, in the context of ghrelin O
      acyltransferase (GOAT) expression. METHODS: We conducted a clinical study of 30
      subjects focusing on the following points: 1) the effects of H. pylori infection
      on the concentrations of circulating ghrelin isoforms and on ghrelin and GOAT
      mRNA expression in the gastric mucosa, and 2) the effects of H. pylori
      eradication on the same parameters. RESULTS: The plasma acyl-ghrelin and desacyl
      ghrelin concentrations of 16 H. pylori positive participants were significantly
      lower than those of 14 H. pylori negative controls. The acyl-ghrelin/desacyl
      ghrelin ratio was not significantly different between the H. pylori positive and
      H. pylori negative participants. The levels of ghrelin and GOAT mRNA in the
      gastric mucosa were significantly lower in the H. pylori positive participants
      than in the H. pylori negative controls. In 11 subjects in whom H. pylori
      eradication was successful, their plasma acyl-ghrelin levels tended to increase
      after H. pylori eradication, but the difference was not significant; however,
      their plasma desacyl-ghrelin levels were significantly reduced. Although gastric
      ghrelin mRNA expression increased significantly after H. pylori eradication,
      gastric GOAT mRNA expression tended to increase but was not significantly
      altered. CONCLUSION: H. pylori status might affect the host's nutritional status
      through changes in the plasma levels of ghrelin isoforms and the gastric
      expression levels of ghrelin and GOAT mRNA.

PMID- 22483416
TI  - Habituation of visual evoked responses in neonates and fetuses: a MEG study.
AB  - In this study we aimed to develop a habituation paradigm that allows the
      investigation of response decrement and response recovery and examine its
      applicability for measuring the habituation of the visually evoked responses
      (VERs) in neonatal and fetal magnetoencephalographic recordings. Two paradigms,
      one with a long and one with a short inter-train interval (ITI), were developed
      and tested in separate studies. Both paradigms consisted of a train of four light
      flashes; each train being followed by a 500Hz burst tone. Healthy pregnant women
      underwent two prenatal measurements and returned with their babies for a neonatal
      investigation. The amplitudes of the neonatal VERs in the long-ITI condition
      showed within-train response decrement. An increased response to the auditory
      dishabituator was found confirming response recovery. In the short-ITI condition,
      neonatal amplitude decrement could not be demonstrated while response recovery
      was present. In both ITI conditions, the response rate of the cortical responses
      was much lower in the fetuses than in the neonates. Fetal VERs in the long-ITI
      condition indicate amplitude decline from the first to the second flash with no
      further decrease. The long-ITI paradigm might be useful to investigate
      habituation of the VERs in neonates and fetuses, although the latter requires
      precaution.

PMID- 22483418
TI  - Radial artery pulse wave analysis for non-invasive assessment of coronary artery
      disease.
AB  - BACKGROUND: Angiographically-normal coronary arteries are reported in 10-20% of
      patients undergoing diagnostic coronary angiography despite screening with risk
      factors and functional tests. We sought to validate and determine the clinical
      value of radial artery pulse wave analysis (PWA), a simple, quick and non
      invasive marker of central artery stiffness and define its ability to predict
      coronary artery disease in high-risk patients. MATERIALS AND METHODS: 531
      consecutive patients referred for elective coronary angiography, irrespective of
      previous co-morbidity, were assessed in a prospective, multicenter observational
      study [the Alternative Risk Markers in Coronary Artery Disease (ARM-CAD) study].
      RESULTS: Mean age was 65 +/- 11 years, 33% were women, 18% had impaired left
      ventricular function and 22% a prior myocardial infarction. Angiography
      demonstrated normal coronary arteries in 20% of participants. The only
      independent associations with this outcome were younger age, female gender,
      absence of diabetes and PWA-derived central augmentation pressure <24 mm Hg. The
      odds ratio for the latter after adjustment for medications and baseline risk
      factors (including blood pressure, high-sensitivity C-reactive protein and B-type
      natriuretic peptide) was 3.4 (95% CI 1.2 to 9.5; p=0.021). The specificity for
      the multivariate model that included PWA was 95.7% with a receiver operator curve
      area of 0.876. Validation studies suggested that systolic variables from PWA were
      robust regardless of waveform quality and similar to measured aortic pressures
      (mean difference 2.7 mm Hg). CONCLUSIONS: Assessment of radial artery waveforms
      is a useful non-invasive clinical test that can stratify the likelihood of
      coronary disease and assist in identifying patients who require diagnostic
      angiography.

PMID- 22483419
TI  - Dairy intake and coronary heart disease or stroke--a population-based cohort
      study.
AB  - AIM: This study aimed to investigate the relationship between total dairy intake
      and dairy subtypes (high-fat dairy, low-fat dairy, milk and milk products, cheese
      and fermented dairy) with incident coronary heart disease (CHD) and stroke.
      METHODS: EPIC-NL is a prospective cohort study among 33,625 Dutch men and women.
      At baseline (1993-1997), dairy intake was measured with a validated food
      frequency questionnaire (FFQ). The incidence of both fatal and non-fatal CHD and
      stroke was obtained by linkage to the national registers. RESULTS: During 13
      years follow-up, 1648 cases of CHD and 531 cases of stroke were documented. Total
      dairy intake was not significantly associated with risk of CHD (hazard ratio per
      standard deviation (SD) increase=0.99; 95%-CI: 0.94-1.05) or stroke (0.95; 0.85
      1.05) adjusted for lifestyle and dietary factors. None of the dairy subtypes was
      to CHD, while only fermented dairy tended to be associated (p=0.07) with a lower
      risk of stroke (0.92; 0.83-1.01). Hypertension appeared to modify the association
      of total and low-fat dairy with CHD (p interaction<0.02). Among participants
      without hypertension, but not among hypertensive participants, total (0.92; 0.85
      1.02) and low-fat (0.94; 0.87-1.02) dairy tended to be associated with a lower
      risk of CHD. CONCLUSION: Our results provide no evidence that dairy products are
      associated with risk of CHD or stroke. High intakes of total and low-fat dairy
      may be associated with a lower risk of CHD among participants without
      hypertension, while fermented dairy could be associated with a reduced risk of
      stroke.

PMID- 22483420
TI  - Combination cell therapy for the treatment of acute myocardial infarction.

PMID- 22483421
TI  - Additive impact of diabetes mellitus on patients with metabolic syndrome and
      acute ST-segment elevation myocardial infarction undergoing primary percutaneous
      coronary intervention.

PMID- 22483422
TI  - Detecting and resolving inconsistencies between domain experts' different
      perspectives on (classification) tasks.
AB  - OBJECTIVES: The work reported here focuses on developing novel techniques which
      enable an expert to detect inconsistencies in 2 (or more) perspectives that the
      expert might have on the same (classification) task. The high level task which
      the experts (physicians) had set themselves was to classify, on a 5-point
      severity scale (A-E), the hourly reports produced by an intensive care unit's
      patient management system. METHOD: The INSIGHT system has been developed to
      support domain experts exploring, and removing inconsistencies in their
      conceptualization of a task. We report here a study of intensive care physicians
      reconciling 2 perspectives on their patients. The 2 perspectives provided to
      INSIGHT were an annotated set of patient records where the expert had selected
      the appropriate category to describe that snapshot of the patient, and a set of
      rules which are able to classify the various time points on the same 5-point
      scale. Inconsistencies between these 2 perspectives are displayed as a confusion
      matrix; moreover INSIGHT then allows the expert to revise both the annotated
      datasets (correcting data errors, or changing the assigned categories) and the
      actual rule-set. RESULTS: Each of the 3 experts achieved a very high degree of
      consensus (~97%) between his refined knowledge sources (i.e., annotated hourly
      patient records and the rule-set). We then had the experts produce a common rule
      set and then refine their several sets of annotations against it; this again
      resulted in inter-expert agreements of ~97%. The resulting rule-set can then be
      used in applications with considerable confidence. CONCLUSION: This study has
      shown that under some circumstances, it is possible for domain experts to achieve
      a high degree of correlation between 2 perspectives of the same task. The experts
      agreed that the immediate feedback provided by INSIGHT was a significant
      contribution to this successful outcome.

PMID- 22483423
TI  - New advances in juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous disorders
      of chronic arthritis in childhood with no apparent etiology. Juvenile idiopathic
      arthritis is the most common pediatric rheumatic disease and is associated with
      significant long-term morbidity and mortality. There have been major advances in
      recent years in our understanding of the pathogenesis of JIA, the definition of
      disease control, and biological treatments for JIA. Multiple environmental and
      genetic factors have been linked with the onset and / or the exacerbation of JIA,
      including perinatal factors, viral and bacterial infections, epigenetic factors,
      and malnutrition. However, no single causative factor has been identified to
      date. As our understanding of the complex network of immune cells and
      inflammatory cytokines has improved, biologics have been developed to modulate
      the inflammatory processes. Indeed, a number of such biologics have been
      demonstrated effective for the treatment of JIA. Although biologic agents may
      alleviate the inflammation associated with JIA and prevent disability caused by
      joint destruction, continued and comprehensive observation is required to
      determine the long-term outcomes associated with such treatment.

PMID- 22483424
TI  - Adhesion family of G protein-coupled receptors and cancer.
AB  - The adhesion-class G protein-coupled receptors (adhesion-GPCRs) constitute the
      second largest GPCR sub-family in humans. Adhesion-GPCRs are defined by the
      chimeric structure of an unusually large extracellular cell-adhesion domain and a
      GPCR-like seven-pass transmembrane domain. Adhesion-GPCRs are hence expected to
      display both cellular adhesion and signaling functions in many biological
      systems. Adhesion-GPCRs are normally expressed in the central nervous, immune,
      and reproductive systems in a cell type- or tissue-restricted fashion. However,
      aberrant expression of distinct adhesion-GPCR molecules has been identified in
      various human cancers with some of the receptors closely associated with cancer
      development. Tumor-associated adhesion-GPCRs are thought to involve in
      tumorigenesis by affecting the growth of tumor cells, angiogenesis, tumor cell
      migration, invasion and metastasis either positively or negatively. Furthermore,
      some adhesion-GPCRs are considered potential biomarkers for specific types of
      cancers. In this review article, the expressional characteristics and functional
      role of cancer-associated adhesion-GPCRs are discussed in depth.

PMID- 22483425
TI  - A comparison between the efficacy of Bio-Oss, hydroxyapatite tricalcium phosphate
      and combination of mesenchymal stem cells in inducing bone regeneration.
AB  - BACKGROUND: Recently, tissue engineering has been introduced as a regenerative
      treatment for bone defects. There is some evidence showing bone regeneration from
      mesenchymal stem cells (MSC) loaded on hydroxyapatite beta-tricalcium phosphate
      (HA/TCP) as a scaffold in large defects. This study aimed to compare the quality
      and quantity of regenerated bone using Bio-Oss, HA/TCP and MSC loaded HA/TCP
      scaffolds. METHODS: Mesenchymal stem cells were aspirated from iliac crest bone
      marrow after extracting the first, second and third premolars and the first molar
      in five mature hybrid dogs. The cells were cultured and their osteogenic
      differentiation potential was evaluated after the third cell passage using
      Alizarin red staining in experimental conditions. The HA/TCP scaffold (3 * 3 * 3
      mm) was loaded with undifferentiated mesenchymal stem cells. Bilateral bone
      defects were then prepared in the jaws using trephine burs. The defects were
      randomly filled with HA/TCP, Bio-Oss, or HA/TCP + MSCs. One defect served as a
      control and was left as an empty cavity. All defects except the control defect
      were covered with an absorbable membrane. Histological and histomorphometric
      evaluations were conducted after 6 weeks and data were subjected to analysis of
      variance (ANOVA) (p < 0.05). RESULTS: The empty cavity demonstrated more bone
      formation (60.80%) than the HA/TCP (44.93%) and Bio-Oss (40.60%) (p < 0.05)
      groups. However, the difference from the HA/TCP + MSCs group was not significant
      (46.38%) (p > 0.05). CONCLUSION: An MSC-loaded HA/TCP scaffold is a more
      effective alternative than Bio-OSS or HA/TCP in inducing bone regeneration.

PMID- 22483426
TI  - The dilemma in the diagnosis of acute scrotum: clinical clues for differentiating
      between testicular torsion and epididymo-orchitis.
AB  - BACKGROUND: Acute painful scrotum is one of the most challenging urological
      emergencies. Irreversible parenchymal damage will develop if a testicle is
      twisted. The aim of the study was to determine the importance of different
      clinical clues to help differentiate the causes of this devastating condition.
      METHODS: The medical charts of teenagers with acute scrotal pain between January
      2003 and December 2008 were reviewed retrospectively. RESULTS: Seventy-six
      patients were included in this study, including 47 initially suspected of having
      testicular torsion and 29 suspected of having epididymo-orchitis. Testicular
      torsion was confirmed in 39 of the suspected 47 cases after surgical exploration.
      Twnety-one of these 39 testicular torsion patients underwent orchiectomy, and 18
      were rescued and underwent orchiopexy. The mean pain duration was significantly
      longer in the orchiectomy group than the orchiopexy group (38.05 hours vs 14.14
      hours, p = 0.009). In the testicular torsion group, fewer patients had elevated C
      reactive protein levels no patients had pyuria, and the pain duration was shorter
      compared with the epididymo-orchitis group (5/11 vs 13/22 [p = 0.045], 0/28 vs
      8/28 [p = 0.004] and 27.0 vs 74.5 hours [p = 0.0003], respectively). The
      sensitivity of color Dopper ultrasound in diagnosing testicular torsion and
      epididymo-orchitis was 84.09% vs 92.59%. Logistic regression for multivariate
      analysis showed that left side manifestation and pain duration were significantly
      different between testicular torsion and epididymo-orchitis with odds ratios of
      4.76, p = 0.020 and 0.98, p = 0.029, respectively. CONCLUSIONS: Pain duration and
      left side manifestation are independent risk factors of testicular torsion.
      Prompt surgical exploration should be done if testicular torsion is highly
      suspected.

PMID- 22483427
TI  - The influence of self-monitoring blood glucose frequency on the oscillation of
      hemoglobin A1c and chronic complications.
AB  - BACKGROUND: A fluctuating blood glucose level is one of the risks of chronic
      complications in diabetes. Previous studies indicated that hemoglobin A1c (HbA1c)
      values apparently improved after initiation of self-monitoring blood glucose
      (SMBG). The purpose of this study is to investigate the relationship between the
      frequency of SMBG, long-term fluctuatation of HbA1c, and risks of chronic
      complications in diabetes. METHODS: We enrolled 1052 patients with type 2
      diabetes. The mean follow-up was 4.7 years. The HbA1c level and frequency of SMBG
      were recorded every 3 months. Non-mydriatic retinal photography, semiquantitative
      neuropathy assessment, the lipid profile, serum creatinine level, and urine
      protein were measured at the beginning of the study and then every year. The
      fluctuation in HbA1c throughout the period was expressed as the standard
      deviations (SDs) of all measurements of the HbA1c. RESULTS: The frequency of SMBG
      was significantly and negatively correlated with the SDs of the HbA1c (r = 
      0.553, p < 0.001) but not with the average HbA1c. After controlling for age, sex,
      body mass index, duration of diabetes and comorbidities (dyslipidemia and
      hypertension), the correlation was still apparent (r = -0.511, p = 0.008).
      Patients with progression of nephropathy, neuropathy, and retinopathy, exhibited
      greater fluctuation of HbA1cs (2.38 +/- 0.99 vs. 0.93 +/- 1.16, p-value 0.002;
      0.97 +/- 1.59 vs. 0.90 +/- 0.56, p-value 0.04; 0.99 +/- 1.33 vs. 0.90 +/- 0.56, p
      value 0.04, respectively) and less frequent SMBG (3.2 +/- 2.6 vs. 4.3 +/- 3.1, p
      value 0.02; 3.2 +/- 2.6 vs. 4.1 +/- 3.9, p-value 0.05; 3.0 +/- 3.1 vs. 4.2 +/-
      2.8, p-value 0.01, respectively) than patients without progression of these
      complications. CONCLUSION: This study shows that frequent SMBG decreased the
      fluctuation of HbA1c and decreased microvascular complications. Decreasing
      fluctuation of HbA1c may play an important role in diabetes treatment.

PMID- 22483428
TI  - Two-incision versus modified Watson-Jones total hip arthroplasty in the same
      patients-- a prospective study of clinical outcomes and patient preferences.
AB  - BACKGROUND: The two-incision technique and the modified Watson-Jones technique
      use muscular intervals and avoid muscle cutting in total hip arthroplasty (THA).
      However these two techniques have not been compared. METHODS: A prospective
      randomized study of clinical outcomes and patient preferences was performed in 20
      patients who had a two-incision THA in one hip and a modified Watson-Jones THA in
      the other between January 2004 and August 2007. The 20 patients were randomized
      equally to the two-incision first or the modified Watson-Jones first group. After
      the second surgery, patients were asked about their preferences for one of the
      two techniques and clinical results were analyzed. RESULTS: After a minimal
      follow-up of 2 years, there were no differences in the hospital course, clinical
      results, functional outcomes, and radiographic results between techniques.
      However more patients (70%) preferred the two-incision side to the modified
      Watson-Jones side in the first 6 months regardless which procedure was performed
      first. CONCLUSION: Given the similarity of these two techniques in cup
      implantation and with only a difference in femoral stem implantation, we think
      that the difference in patient preferences in the early postoperative period
      might be related to the surgical dissection and manipulation of the hip with the
      modified Watson-Jones technique.

PMID- 22483429
TI  - Diagnostic efficacy of ultrasonography-guided fine needle aspiration biopsy in
      evaluating salivary gland malignancy.
AB  - BACKGROUND: Salivary gland masses constitute a diagnostic challenge in daily
      clinical practice and tissue sampling is required to establish a diagnosis. We
      aimed to evaluate the efficacy of ultrasonography-guided fine needle aspiration
      biopsy (UGFNAB) in the diagnosis of salivary gland lesions. METHODS: From January
      2007 to September 2010, a total of 158 patients who underwent both UGFNAB and
      surgical excision for salivary gland mass lesions were included in this study.
      Patients with insufficient sampling or inconclusive cytology diagnosis were
      excluded from the analysis of diagnostic accuracy of UGFNAB. RESULTS: UGFNAB
      yielded sufficient sampling for analysis in 137 patients, leading to a diagnostic
      yield of 86.7%. Among these 137 patients, 24 patients were confirmed to have
      malignant tumors. The sensitivity, specificity and accuracy of UGFNAB for
      malignancy were 66.7%, 98.2%, and 92.7%, respectively. No UGFNAB-related
      complications were encountered. CONCLUSIONS: UGFNAB of salivary gland masses is a
      safe technique that offers high specificity and accuracy but moderate diagnostic
      yield and sensitivity.

PMID- 22483430
TI  - Surgical management of giant hepatic hemangiomas: complications and review of the
      literature.
AB  - BACKGROUND: Hepatic hemangiomas are the most common benign hepatic tumors, and
      they are usually asymptomatic with normal liver function. When hepatic
      hemangiomas reach 4 cm, we define them as giant hemangiomas. Treatment options
      for giant hemangiomas are observation, surgical resection, and transcatheter
      arterial embolization. The aim of this study was to identify the risk factors for
      surgical complications. METHODS: In this study, the records of 61 patients with
      giant hepatic hemangiomas treated with surgical resection at Chang Gung Memorial
      Hospital, Linkou were retrospectively reviewed. Data on clinical variables
      including symptoms, the size, number, and location of the tumors, preoperative
      liver function tests, operative method, operation time, and operative blood loss
      were collected and analyzed. RESULTS: There were 8 patients (13.1%, 95%
      confidence interval 5.8% to 24.2%) with complications after resection or
      enucleation. Postoperative complications were associated with large tumor size (p
      = 0.021) and tumors that were symptomatic (p = 0.017). In addition, complications
      were associated with greater use of intraoperative inflow control (p = 0.053),
      longer operative time (p = 0.001), and greater intraoperative blood loss (p =
      0.022). Most complications could be treated conservatively, but invasive
      interventions such as endoscopic retrograde cholangiopancreatography and
      percutaneous transhepatic cholangial drainage were required for management of
      grade III complications. CONCLUSIONS: Most giant hepatic hemangiomas can be
      treated with enucleation or resection. Important factors associated with
      complications were large tumor size, the presence of symptoms, surgical bleeding,
      and prolonged surgery. Most complications were grade I and could be treated
      conservatively. Both resection and enucleation were relatively safe with an
      acceptable complication rate (13.1%) and no mortality in our study.

PMID- 22483431
TI  - Hemoglobin variability does not predict mortality in peritoneal dialysis
      patients.
AB  - BACKGROUND: Hemoglobin variability in hemodialysis patients treated with
      erythropoiesis-stimulating agents has been used to evaluate mortality and
      comorbidity. Different outcomes have been reported in American and European
      hemodialysis patients. There are, however, few studies of the effects of
      hemoglobin variability in peritoneal dialysis patients. METHODS: We investigated
      hemoglobin variability in 363 peritoneal dialysis patients over 2 years to
      evaluate mortality and the association with comorbidity, peritonitis, and
      hospitalization. The hemoglobin of all patients selected for the study had been
      monitored for at least 6 months (April 2008 to September 2008). We assessed
      hemoglobin variability as fluctuations from the target hemoglobin level (11-12.5
      g/dL). We defined the following 6 patient groups on the basis of hemoglobin
      patterns: consistently low (< 11 g/dL), consistently target range (11-12.5 g/dL),
      consistently high (> 12.5 g/dL), low-amplitude fluctuation with low hemoglobin
      levels, low-amplitude fluctuation with high hemoglobin levels, and high amplitude
      fluctuation. RESULTS: Only 2% of patients maintained a stable hemoglobin level
      within the target range and 46.8% of patients exhibited consistently low
      hemoglobin levels. After 2 years of observation, there was no difference in
      mortality as assessed by Kaplan-Meier analysis. There were also no differences in
      peritonitis and hospitalization between the 6 groups. However, the length of
      hospital stay was longer in the high amplitude fluctuation group (p = 0.008).
      CONCLUSION: Hemoglobin variability does not predict mortality in peritoneal
      dialysis patients.

PMID- 22483433
TI  - Size discrimination and detection capabilities of single-particle ICPMS for
      environmental analysis of silver nanoparticles.
AB  - The detection capabilities of single particle inductively coupled plasma-mass
      spectrometry (spICPMS) with respect to particle size and number concentrations
      are investigated for the case of silver nanoparticles (ca. 20-80 nm). An
      iterative algorithm was developed where particle measurement events were
      distinguished as outliers from the more continuous dissolved ion signal if the
      measured intensity was more than five times the standard deviation of the whole
      data set. The optimal dwell time for 40-80 nm particles, limiting both incomplete
      and multiple particle events, was 5 ms. The smallest detectable particle size
      (ca. 20 nm) is mainly limited by the overlap of particle events and dissolved
      signal that increases with noise on both signals. The lowest measurable number
      concentration is limited by the relative frequency of erroneously identified
      particle events, a limit that can be reduced by acquiring more data points.
      Finally, the potential of spICPMS for environmental detection of nanoparticles is
      demonstrated for a wastewater treatment plant effluent sample.

PMID- 22483432
TI  - The influence of lipids on voltage-gated ion channels.
AB  - Voltage-gated ion channels are responsible for transmitting electrochemical
      signals in both excitable and non-excitable cells. Structural studies of voltage
      gated potassium and sodium channels by X-ray crystallography have revealed atomic
      details on their voltage-sensor domains (VSDs) and pore domains, and were put in
      context of disparate mechanistic views on the voltage-driven conformational
      changes in these proteins. Functional investigation of voltage-gated channels in
      membranes, however, showcased a mechanism of lipid-dependent gating for voltage
      gated channels, suggesting that the lipids play an indispensible and critical
      role in the proper gating of many of these channels. Structure determination of
      membrane-embedded voltage-gated ion channels appears to be the next frontier in
      fully addressing the mechanism by which the VSDs control channel opening.
      Currently electron crystallography is the only structural biology method in which
      a membrane protein of interest is crystallized within a complete lipid-bilayer
      mimicking the native environment of a biological membrane. At a sufficiently high
      resolution, an electron crystallographic structure could reveal lipids, the
      channel and their mutual interactions at the atomic level. Electron
      crystallography is therefore a promising avenue toward understanding how lipids
      modulate channel activation through close association with the VSDs.

PMID- 22483434
TI  - Combating antimicrobial resistance: antimicrobial stewardship program in Taiwan.
AB  - Multi-drug-resistant organisms are increasingly recognized as a global public
      health issue. Healthcare-associated infection and antimicrobial resistance are
      also current challenges to the treatment of infectious diseases in Taiwan.
      Government health policies and the health care systems play a crucial role in
      determining the efficacy of interventions to contain antimicrobial resistance.
      National commitment to understand and address the problem is prerequisite. We
      analyzed and reviewed the antibiotic resistance related policies in Taiwan, USA,
      WHO and draft antimicrobial stewardship program to control effectively antibiotic
      resistance and spreading in Taiwan. Antimicrobial stewardship program in Taiwan
      includes establishment of national inter-sectoral antimicrobial stewardship task
      force, implementing antimicrobial-resistance management strategies, surveillance
      of HAI and antimicrobial resistance, conducting hospital infection control,
      enforcement of appropriate regulations and audit of antimicrobial use through
      hospital accreditation, inspection and national health insurance payment system.
      No action today, no cure tomorrow. Taiwan CDC would take a multifaceted, evidence
      based approach and make every effort to combat antimicrobial resistance with
      stakeholders to limit the spread of multi-drug resistant strains and to reduce
      the generation of antibiotic resistant bacteria in Taiwan.

PMID- 22483435
TI  - Damage in brain development by morpholino knockdown of zebrafish dax1.
AB  - DAX1 is an orphan nuclear receptor and involved in development of steroidogenic
      organs, which activates transcription of genes involved in steroidogenesis. In
      this study, we analyzed the function of the zebrafish dax1 during early
      development of central nervous systems to appear unidentified aspects of DAX1 and
      decrease confusions concerned with functions of DAX1 in early development of
      vertebrates. By whole-mount in situ hybridization of embryo at the 32 h post
      fertilization (hpf), expression of zebrafish dax1 was detected around the
      forebrain, midbrain, hindbrain, and the extending tail tip. Embryos injected with
      zebrafish dax1 morpholino antisense nucleotide (MO) exhibited delayed
      development. When the developmental stage of wild type embryos was at Prim-15 (32
      hpf), zebrafish dax1MO injected embryos were at Prim-5 (24 hpf). Concurrently
      with developmental delay, the MO injected embryos showed high mortality. At 48
      hpf, the MO injected embryos exhibited abnormal development in the central
      nervous systems. The enlarged tectum and the protruded rhombomeres were observed.
      Moreover, development of central nervous systems, especially midbrain-hindbrain
      boundary, became narrower. At 5 day post fertilization, the MO injected embryos
      formed edemas around head, pericardial sac and abdomen. Collectively, our results
      indicated that the zebrafish dax1 is important for brain development.

PMID- 22483436
TI  - Neurobehavioral effects of exposure to traffic-related air pollution and
      transportation noise in primary schoolchildren.
AB  - BACKGROUND: Children living close to roads are exposed to both traffic noise and
      traffic-related air pollution. There are indications that both exposures affect
      cognitive functioning. So far, the effects of both exposures have only been
      investigated separately. OBJECTIVES: To investigate the relationship between air
      pollution and transportation noise on the cognitive performance of primary
      schoolchildren in both the home and school setting. METHODS: Data acquired within
      RANCH from 553 children (aged 9-11 years) from 24 primary schools were analysed
      using multilevel modelling with adjustment for a range of socio-economic and life
      style factors. RESULTS: Exposure to NO(2) (which is in urban areas an indicator
      for traffic-related air pollution) at school was statistically significantly
      associated with a decrease in the memory span length measured during DMST
      (chi(2)=6.8, df=1, p=0.01). This remained after additional adjustment for
      transportation noise. Statistically significant associations were observed
      between road and air traffic noise exposure at school and the number of errors
      made during the 'arrow' (chi(2)=7.5, df=1, p=0.006) and 'switch' (chi(2)=4.8,
      df=1, p=0.028) conditions of the SAT. This remained after adjustment for NO(2).
      No effects of air pollution exposure or transportation noise exposure at home
      were observed. Combined exposure of air pollution and road traffic noise had a
      significant effect on the reaction times measured during the SRTT and the 'block'
      and the 'arrow' conditions of the SAT. CONCLUSIONS: Our results provide some
      support that prolonged exposure to traffic-related air pollution as well as to
      noise adversely affects cognitive functioning.

PMID- 22483437
TI  - A cohort study relating urban green space with mortality in Ontario, Canada.
AB  - Parks and green space areas are important to human health for psychological and
      physiological reasons. There have been few evaluations of access to green space
      on mortality. This paper describes a cohort study of approximately 575,000
      adults, 35 years of age and older, who resided in 10 urban areas in Ontario,
      Canada, between 1982 and 1986. Individuals were identified from income tax
      filings, and vital status was determined up to December 31, 2004 through record
      linkage to the Canadian Mortality Data Base. Place of residence was defined by
      postal code data that were extracted from income tax filings. Urban green space
      was defined by Landsat satellite retrievals with the Normalized Difference
      Vegetation Index and this was assigned to individuals' place of residence at
      inception into the cohort using both a 30 m grid cell and a 500 m buffer. The
      proportional hazards model was used to estimate rate ratios (RRs) and their
      corresponding 95% confidence intervals (CI) for selected underlying causes of
      death. The rate ratios were adjusted for income, marital status, ambient air
      pollution, and contextual neighborhood characteristics. About 187,000 subjects
      died during follow-up. An increase in the interquartile range of green space,
      using a 500 m buffer, was associated with reduced non-accidental mortality
      (RR=0.95, 95% CI=0.94-0.96). Reductions in mortality with increased residential
      green space were observed for each underlying cause of death; the strongest
      association was found for respiratory disease mortality (RR=0.91, 95% CI=0.89
      0.93). Risk estimates were essentially unchanged after adjusting for ambient air
      pollution. Our study suggests that green space in urban environments was
      associated with long-term reduction in mortality although this finding should be
      interpreted cautiously as this association may be influenced by residual
      confounding of sociodemographic and lifestyle factors. Further research is needed
      to: confirm these findings, better understand the relationships between access to
      green space and behavioral risk factors for mortality, and identify what green
      space characteristics may confer the greatest health benefit.

PMID- 22483438
TI  - Hemoglobin immobilized with modified "fish-in-net" approach for the catalytic
      removal of aniline.
AB  - Blood is a waste product of the slaughter industry, while its main component
      hemoglobin (Hb) is a pseudo-peroxidase which is able to oxidize polycyclic
      aromatic hydrocarbons (PAHs) in the presence of H(2)O(2). In order to use Hb for
      wastewater treatment, we encapsulated it in silica-based matrix by modified "fish
      in-net" approach. The as-synthesized catalysts were characterized by SEM, TEM,
      BET and solid-state UV-vis spectroscopy. It was found that Hb was partially
      homogeneously dispersed in microspheres and showed more stable peroxidase-like
      activity than free Hb. Moreover, it had substantially increased storage stability
      as well as pH stability. It was used as biocatalyst to remove aniline in aqueous
      solution and gave a reduction of 65% aniline removal, while 76% in the presence
      of additive PEG. No significant activity loss was observed after ten runs. These
      experimental results suggest that the resultant product was a promising
      biocatalyst for aromatic wastewater treatment.

PMID- 22483439
TI  - Bi2MoO6 ultrathin nanosheets on ZnTiO3 nanofibers: a 3D open hierarchical
      heterostructures synergistic system with enhanced visible-light-driven
      photocatalytic activity.
AB  - The 3D open Bi(2)MoO(6)/ZnTiO(3) hierarchical heterostructures with Bi(2)MoO(6)
      ultrathin nanosheets (<10nm) grown on hexagonal-phase ZnTiO(3) nanofibers were
      fabricated by combining the electrospinning technique and solvothermal method.
      And, the Bi(2)MoO(6)/ZnTiO(3) hierarchical heterostructures had remarkable light
      absorption in the visible region. The photocatalytic studies revealed that the
      hierarchical heterostructures system exhibited exceptional photocatalytic
      activity in visible-light degradation of Rhodamine B, which might be attributed
      to the synergistic system with excellent charge separation characteristics and
      the unique morphology of Bi(2)MoO(6) nanosheets with the extended absorption in
      the visible light region. What is more, the 3D open structure supported on
      nanofibrous candidates possessed large surface areas and excellent recyclability.

PMID- 22483440
TI  - The use of lightweight expanded clay aggregate (LECA) as sorbent for PAHs removal
      from water.
AB  - Lightweight expanded clay aggregate (LECA) has been explored as a sorbent for the
      removal of PAHs (phenanthrene, fluoranthene and pyrene) from water. The efficacy
      of LECA as a sorbent for PAHs was assessed using contact time, mass of sorbent
      and sorption isotherms in a series of batch experiments. Maximum (optimum)
      sorption was reached at 21 h after which the amount of PAHs sorbed remained
      almost constant. Batch experiments were conducted by shaking a 100ml solution
      mixture of individual PAHs (containing 0.02 mg/L) with LECA. The maximum sorption
      was 70.70, 70.82 and 72.12%, respectively for phenanthrene, fluoranthene and
      pyrene when a mass of 0.2 g of sorbent was used. There was an increase in
      sorption as a result of an increase in mass of sorbent until a maximum was
      reached at a mass of 4.0 g LECA with 92.61, 93.91 and 94.15% sorption of
      phenanthrene, fluoranthene and pyrene respectively. Sorption data were fitted to
      the linearised forms of the Freundlich and Langmuir isotherm models to determine
      the water-LECA partitioning coefficient. Physical sorption caused by the aromatic
      nature of the compounds was the main mechanism that governed the removal process
      while the hydrophobicity of the PAHs also influenced the sorption capacity. LECA
      can be used as an alternative method for aqueous PAHs removal.

PMID- 22483441
TI  - Chlorination of Microcystis aeruginosa suspension: cell lysis, toxin release and
      degradation.
AB  - Although the release of intracellular toxins after chlorination has been
      reported, the relation between cell lysis and the release and degradation of
      toxins during chlorination has not been well illustrated. This study used
      Microcystis aeruginosa to investigate the release and degradation behaviors of
      toxins after its exposure to chlorine at different doses for prolonged contact
      time. Scanning electron microscopy (SEM) analysis indicates no considerable
      change in the morphology for most algae cells. However, the release of
      intracellular K(+) and intracellular organic matter (IOM) did occur, and the
      significant K(+) release of 63% was observed even at chlorine exposure as low as
      0.8 mg/L min. The damage of cell membrane was faster than the release of
      intracellular MCLR at all chlorine doses. Extracellular MCLR accumulated as a
      result of the fact that intracellular MCLR released from damaged cells faster
      than it was degraded by chlorine, especially at low dose of chlorine (0.8 mg/L).
      A maximum level of extracellular toxin at a contact time of 60, 30 and 1 min was
      observed at chlorine doses of 1.2, 1.6 and 2.0mg/L, respectively. In addition,
      Cl(2) consumption (%), toxin release and degradation (%), and cells lysis (%)
      were well related.

PMID- 22483442
TI  - Enantioselective phytotoxicity of metolachlor against maize and rice roots.
AB  - Rac-metolachlor, a widely used chloracetanilide herbicide, is now being replaced
      by S-metolachlor in many countries. The enantioselective effects of rac- and S
      metolachlor on root growth of maize and rice was studied in hydroponics. Visible
      morphological changes in root growth were observed after treatment with rac- or S
      metolachlor. The main root and lateral roots were shorter in length, and the
      number of lateral roots was reduced. The half inhibition (IC(50,5d)) values for
      root length of rac- and S-metolachlor were 18.86 and 10.61 MUM, respectively, for
      maize, and 7.33 and 5.35 MUM, respectively, for rice. The root system activity
      after treatment with rac- or S-metolachlor was lower than that of the control,
      while the root membrane permeability was higher. The activities of superoxide
      dismutase, peroxidase, and catalase in the roots were lower after rac- or S
      metolachlor treatment compared to those of the control, while the malondialdehyde
      content was higher. After rice was treated with 3.1 MUM rac- or S-metolachlor,
      the cell wall separated from the cell membrane, and some destruction of nuclei
      and organelles was observed. The entire cell was destroyed after treatment with
      12.4 MUM rac- or S-metolachlor. The results showed that S-metolachlor has
      stronger effects than rac-metolachlor on crop roots.

PMID- 22483443
TI  - The interplay between gender, race and weight status: self perceptions and social
      consequences.
AB  - This paper uses data from nearly 15,000 young adult respondents to the Add Health
      survey to examine racial and gender differences in the perceptions and social
      rewards to weight. The data include information on several typically unmeasured
      domains: self-perceptions of ideal weight, attractiveness ratings, and measured
      weight information, along with ties to a series of adult outcomes. Results show
      important gender and racial differences in ideal weight as well as differences
      for both self-perceived attractiveness and interviewer rated attractiveness.
      Findings also suggest the existence of large differences in socio-cultural
      rewards and sanctions for weight status. Black respondents, particularly women,
      appear to receive lower "obesity penalties" in both their self-perceived and
      interviewer accessed attractiveness ratings than other groups. These findings
      suggest the need to consider new classes of policies directed at shifting
      relative social benefits and consequences to weight status. 

PMID- 22483444
TI  - Assessment of families of children with cerebral palsy of the "CP-graph on
      treatment modalities for gross motor function".

PMID- 22483445
TI  - Torus mandibularis bone chips combined with platelet rich plasma gel for
      treatment of intrabony osseous defects: clinical and radiographic evaluation.
AB  - The use of platelet rich plasma (PRP) gel in combination with torus mandibularis
      offers a potentially useful treatment for periodontal osseous defects. Whether
      this combination enhances the outcome of periodontal regenerative therapy is not
      known. This study compared the effectiveness of torus mandibularis bone chips
      alone and when combined with autogenous PRP gel in treating periodontal osseous
      defects. 24 sites from 12 patients were selected using a split mouth design and
      determined by a double-blind, randomized, controlled clinical trial. Both sites
      received a full-thickness mucoperiosteal flap; one intrabony defect was filled
      with torus mandibularis bone chips alone and the other with torus mandibularis
      bone chips mixed with PRP gel. There was a 57% gain in the clinical attachment
      level and 60% reduction in the probing depth for torus mandibularis alone
      compared to 72% and 68% for sites treated with torus mandibularis and PRP gel (p
      <= 0.01). There was a statistically significant difference in the bone dentistry
      and the marginal bone loss at sites with PRP gel compared to those without gel (p
      <= 0.01). The use of mandibular tori as autogenous bone graft combined with PRP
      gel showed a significant improvement in the clinical outcome of periodontal
      therapy than mandibular tori alone.

PMID- 22483446
TI  - Frontofacial advancement by internal distraction devices. A technical
      modification for the management of craniofacial dysostosis in early childhood.
AB  - Normal craniofacial growth is characterized by a different growth pattern of
      neuro- and viscerocranium. In craniofacial dysostosis (CFD) syndromes there is
      complex disturbance of this physiological growth pattern. Modern surgical
      management of CFD is staged with respect to the severity of the deformity, the
      age and the development of the patient. Early single stage management of anterior
      cranial vault deformity and midfacial retrusion in children affected by syndromic
      craniosynostosis is possible when anterior cranial vault remodelling is performed
      together with gradual Le Fort III midfacial advancement. One pair of internal
      distraction devices, placed in accordance with the midfacial growth vector after
      initial cranial vault remodelling, can be sufficient for this purpose. Technical
      aspects of this modified frontofacial advancement procedure are presented and
      discussed based on a case report with a postoperative follow up time of 50
      months.

PMID- 22483447
TI  - Vascularized free tissue transfer for reconstruction of ablative defects in oral
      and oropharyngeal cancer patients undergoing salvage surgery following
      concomitant chemoradiation.
AB  - The purpose of this study was to determine whether chemotherapy delivered
      concurrently with external beam radiation therapy for loco-regionally advanced
      head and neck cancer affects the rate or severity of postoperative complications
      in patients who underwent salvage surgery for recurrent or persistent disease
      with simultaneous microvascular free flap reconstruction. The primary study group
      consisted of patients with head and neck malignancies that had undergone surgical
      salvage with microvascular free flap reconstruction for persistent or recurrent
      disease following definitive radiation or concomitant chemoradiation treatment. A
      group of demographically matched patients who underwent microvascular free flap
      reconstruction for non-malignant and malignant conditions who never received
      radiation were randomly selected to serve as a control group. The study cohort
      was divided according to radiation treatment. The overall success rate of flap
      reconstruction was 92%, with an overall complication rate of 23%. Concurrently
      administered chemotherapy did not appear to affect the type of or the
      complication rate. The results of this investigation indicate that microvascular
      free flap reconstruction of head and neck defects is highly predictable, results
      in relatively few major complications, and suggests that neither radiation alone
      nor concomitant chemoradiation has a statistically significant effect on overall
      flap survival or complication rate.

PMID- 22483448
TI  - The effect of recurrent glomerulonephritis and acute rejection episodes in zero
      human leukocyte antigen-mismatched kidney transplantation.
AB  - BACKGROUND: Although human leukocyte antigen (HLA)-identical renal
      transplantation achieves superior graft outcomes, it does not uniformly allow
      indefinite graft survival. Recurrence of the original disease and effects of
      acute rejection episodes (ARE) may preclude indefinite survival. Herein, we have
      analyzed the factors that affect the graft outcomes among HLA zero-mismatch
      cases. METHODS: We performed a retrospective, single-center study to evaluate the
      effect of recurrent glomerulonephritis (GN) and ARE on outcomes of grafts with
      zero HLA-mismatches (n = 122) versus three to four mismatches (n = 317), and five
      to six mismatches (n = 102). Forty-one percent of patients had GN as underlying
      disease. RESULTS: Overall graft survival was 92.4% at 5 years and 79.6% at 10
      years. HLA incompatibility did not affect graft survival: zero versus three to
      four versus five to six mismatches = 92.8% versus 90.8% versus 95.8% at 5 years
      and 82.5% versus 74.3% versus 85.1% at 10 years, respectively (P = .399).
      Subgroup analysis for subjects with GN revealed that ARE (P = .001) and recurrent
      GN (P = .003) were the risk factors for graft loss, whereas living donation was
      protective (P = .029). ARE was more prevalent with greater HLA incompatibility [0
      (reference) < three to four < five to six mismatches; P = .047 and P = .014].
      However, recurrent GN showed the opposite trend [0 (reference) > three to four >
      five to six mismatches; P = .106 and P = .022]. Furthermore, graft loss due to
      recurrent GN was significant among the HLA zero versus the three- to four
      mismatch group (P = .047). CONCLUSIONS: Graft survival was not affected by the
      degree of HLA incompatibility, which was mainly due to the recurrence of
      underlying disease. Therefore, a main focus should be the management of
      recurrence, especially among HLA-identical kidney transplantations.

PMID- 22483449
TI  - Interstitial fibrosis and tubular atrophy on protocol biopsies at 1 year after
      renal transplantation.
AB  - BACKGROUND: Advancements in immunosuppressive therapy have enabled control of
      early acute rejection and improved long-term kidney transplantation (KT)
      survival. Chronic histopathologic changes influence graft survival rate. We
      examined tubulointerstitial changes at 1 year after KT, focusing on the
      progression of interstitial fibrosis and/or tubular atrophy (IF/TA). METHODS:
      Using the Banff' 07 classification, we assessed the histological findings
      obtained at 1 year after transplantation of 38 patients who underwent the
      procedure between January 2008, and March 2010. In 24 cases, we obtained scores
      for interstitial fibrosis (ci) >1 and/or tubular atrophy (ct) > 1. We classified
      the patients into two groups, namely, less than borderline changes (BCs) (t0, i0,
      or i1; group A) versus BCs and above (t > 1, i2, or i3; group B). We compared
      their baseline data, renal function, and pathological scores. RESULTS: The mean
      serum creatinine levels were 1.06 mg/dL for group A and 1.32 mg/dL for group B.
      The "ct" grading according to the Banff' 07 classification was 0.83 for group A
      and 1.50 for group B (both P < .05). No significant difference was observed with
      respect to the percentage of patients with IF/TA (Banff category 5). CONCLUSION:
      Patients more within 1 year after KT with BCs who show irreversible tubular
      atrophy by biopsy experience impaired renal function. The presence of BC at the
      first year may not be associated with IF/TA.

PMID- 22483450
TI  - Clinical significance of proteinuria at posttransplant year 1 in kidney
      transplantation.
AB  - PURPOSE: Proteinuria in the nontransplant population is a progressive renal
      disease. We analyzed the prevalence and clinical significance of proteinuria as
      well as factors related to its degree at posttransplant year 1 among kidney
      transplant recipients. METHODS: We measured protein in a 24-hour urine among 644
      recipients from January 1996 to December 2010. RESULTS: Among 372 male and 272
      female recipients, the mean amount of urinary protein was 424.4 +/- 1010 mg/d
      (range, 13.88-8691) including 388 (60.2%) subjects with microproteinuria and the
      other 256 (39.8%) with overt proteinuria. Nephrotic range proteinuria was
      observed in 17 (2.6%) and nonnephritic range proteinuria, in 239 (37.1%)
      recipients. The latter cohort was categorized into low-grade proteinuria (n =
      224; 34.8%) and high-grade proteinuria (n = 15; 2.3%). Proteinuria at
      posttransplant 1 year highly correlated with serum creatinine values at
      posttransplant years 1 and 2 as well as estimated glomerular filtration rate but
      not creatinine clearance at postoperative year 2. A greater incidence of graft
      loss was observed among recipients with more severe proteinuria. Males,
      recipients with anti-hepatitis C virus antibody, unrelated donors, anti-thymocyte
      immunoglobulin at the time of reperfusion, maintenance immunosuppression with
      cyclosporine or without mycophenolate mofetil were strongly associated with the
      amount of proteinuria. CONCLUSION: This study demonstrated the prevalence of
      proteinuria in kidney transplant recipient to be high. The presence as well as
      level of proteinuria were predictive markers for inferior allograft function.

PMID- 22483451
TI  - Accompanying renal injuries did not impact graft survival in patients with
      transplant glomerulopathy.
AB  - Transplant glomerulopathy (TG) a morphological feature of chronic active antibody
      mediated rejection, is associated with donor-specific antibody, peritubular
      capillary deposition of C4d, and multilayering of peritubular capillary basement
      membranes. To evaluate the significance of accompanying nonimmunologic injuries
      in TG, we retrospectively reviewed 2839 renal allograft cases at our institute
      among which TG was diagnosed in 81 patients (2.9%). Among TG cases, 48 samples
      showed accompanying diseases such as chronic calcineurin inhibitor toxicity,
      hepatitis viral infection, posttransplant diabetes, and glomerulonephritis.
      Comparing the pure form of TG with TG-mixed diseases, there was no difference in
      patient demography, serum creatinine values, and proteinuria. Among histological
      parameters, severe hyalinosis was more frequently observed among the TG plus
      other diseases group. The two groups did not show significant difference in graft
      survival (P = .216).

PMID- 22483452
TI  - C4d deposition and multilayering of peritubular capillary basement membrane in
      posttransplantation membranous nephropathy indicate its association with antibody
      mediated injury.
AB  - Membranous nephropathy (MN) may develop as recurrence or de novo after
      transplantation. Recently, autoimmune or alloimmune responses to unspecified
      glomerular antigens have been considered as a pathogenetic mechanism. To explore
      the relationship between antibody-mediated injury and posttransplantation MN, we
      tested C4d positivity using polyclonal antibody in renal allograft biopsy samples
      diagnosed as posttransplantation MN. A total of 19 cases (16 males and 3
      females), including 2 recurrent and 7 de novo forms, were the subject of the
      study. On light microscopy, stage II was the most common (n = 9). In addition to
      glomerular capillary immunoglobulin (Ig)G deposits, all but 2 cases having only
      sclerotic glomeruli were C4d-positive in glomerular capillary walls. Twelve cases
      were also positive in cortical peritubular capillaries (PTCs): diffuse in 8 cases
      and focal in 4 cases. Two of 3 cases associated with acute rejection and 3 of 4
      cases associated with chronic rejection were PTC C4d-positive. The frequency of
      C4d positivity in PTCs was significantly higher than that of posttransplantation
      IgA nephropathy (P = .028). In conclusion, a higher frequency of PTC C4d
      positivity suggests an involvement of chronic antibody-mediated injury in the
      evolution of posttransplantation MN.

PMID- 22483453
TI  - Serum total p-cresol and indoxyl sulfate correlated with stage of chronic kidney
      disease in renal transplant recipients.
AB  - BACKGROUND: Uremic toxins are considered cardiovascular and mortality risk
      factors in chronic kidney disease (CKD) patients. Both p-cresol and indoxyl
      sulfate have been shown to induce oxidative stress in vitro and subsequent
      endothelial dysfunction in uremic patients. Our study evaluated the levels of p
      cresol and indoxyl sulfate, and whether they contribute to the progression of CKD
      in transplant recipients. METHODS: We retrospectively evaluated 95 patients who
      had received a transplant from February 1987 to June 2010 in our center; the
      recipients had a mean transplant duration of 5.3 +/- 4.9 years and a mean age of
      47.8 +/- 14.1 years. Among them, 56.8% (54/95) were male. Patients with
      glomerular filtration rate (GFR) >= 60 mL/min/1.73 m(2) were selected for group 1
      (n = 35), and those with GFR < 60 mL/min/1.73 m(2) were selected for group 2 (n =
      60). Demographic and clinical data were compared between groups. Serum and urine
      levels of p-cresol and indoxyl sulfate were also obtained. RESULTS: Baseline
      serum p-cresol and indoxyl sulfate levels were significantly higher in advanced
      CKD stages (P = .001 and <.0001, respectively). Patients at advanced CKD stages
      (group 2) had lower serum levels of hemoglobin and albumin (P < .0001), but
      higher levels of total cholesterol, triglyceride, and uric acid levels (P = .04,
      .04 and .001, respectively). Body mass index, C-reactive protein, and serum
      calcium and phosphate levels showed no significant differences between groups.
      The cut-off value for serum p-cresol between groups was 1.28 umol/L (P = .01),
      and that for the indoxyl sulfate level was 0.98 umol/L (P = .0001). CONCLUSION:
      The serum p-cresol and indoxyl sulfate levels were significantly higher in
      advanced CKD stages in transplant recipients. To evaluate the use of serum p
      cresol and indoxyl sulfate levels as a predictive tool for survival, larger
      clinical studies are needed.

PMID- 22483454
TI  - Role of reactive oxygen species in transforming growth factor-beta1-induced
      extracellular matrix accumulation in renal tubular epithelial cells.
AB  - Tubulointerstitial fibrosis, which is characterized by the progressive
      accumulation of extracellular matrix (ECM), is the main feature of chronic renal
      allograft dysfunction. Transforming growth factor-beta1 (TGF-beta1) is the key
      inducer of tubulointerstitial fibrosis. Plasminogen activator inhibitor-1 (PAI
      1), a major inhibitor of ECM degradation, is increasingly recognized to play an
      important role in renal fibrosis. ECM accumulation is the net result of ECM
      synthesis and degradation. We previously reported that reactive oxygen species
      (ROS) and subsequent activation of mitogen-activated protein kinase (MAPK) are
      required for the TGF-beta1-induced epithelial-to-mesenchymal transition in renal
      proximal tubular epithelial cells. In the present study, we examined the role of
      the ROS-MAPK pathways in TGF-beta1-induced fibronectin and PAI-1 up-regulation in
      renal tubular epithelial cells. Growth arrested, synchronized normal rat kidney
      epithelial (NRK-52E) cells were stimulated with TGF-beta1 (0.2-20 ng/mL) or
      H(2)O(2) (1-500 MUmol/L) in the presence or absence of inhibitors of nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase (diphenyleneiodonium [DPI] and
      apocynin [Apo]) and MAPK (PD98059, an MEK inhibitor, or a p38 MAPK inhibitor) for
      up to 48 hours. Both TGF-beta1 and H(2)O(2) increased fibronectin and PAI-1
      secretion in dose-dependent manners. Chemical inhibition of NADPH oxidase,
      extracellular signal-regulated kinase (ERK), or p38 MAPK all inhibited TGF-beta1
      induced and H(2)O(2)-induced fibronectin and PAI-1 up-regulation. These results
      suggested that NADPH oxidase-mediated ROS and subsequent ERK and p38 MAPK
      activation play important roles in ECM accumulation in the renal
      tubulointerstitium.

PMID- 22483455
TI  - Long-term impact of hypertension on renal allografts.
AB  - OBJECTIVE: We assessed the impact of hypertension on renal transplant function
      and survival in the past decade after introduction of mycophenolate mofetil and
      rituximab. METHODS: We examined the 184 patients who underwent renal
      transplantation from March 1982 to September 1999 and presented at our outpatient
      clinic from 2001 to 2011. They were divided into group 1 with mean systolic blood
      pressure (mSBP) >130 mm Hg and Group 2 with mSBP <130 mm Hg. We compared mean
      serum creatinine (sCr) levels for 9 years and 12-year actuarial graft survival
      rates. Risk factors for graft survival were assessed by Cox regression analysis.
      RESULTS: There were 75 group 1 and 109 group 2 recipients. The mean sCr level of
      group 1 was 1.59 +/- 0.12 mg/dL and that of group 2 1.54 +/- 0.10 mg/dL (P <
      .0001). Of note was that mean sCr levels of group 1 started to increase about 3
      years after transplantation. Although 5-year graft survival rates of both groups
      were 100%, 9- and 12-year rates among group 1 were 97.3% and 90.5%, respectively,
      whereas among group 2 they were 99.1% and 98.1%, respectively (P = .0195). Cox
      univariate and multivariate analyses showed mean SBP to be the only significant
      risk factor for graft survival (P < .05). CONCLUSIONS: We concluded that the
      hypertensive group showed deteriorating renal function from around 3 years after
      transplantation that lowered graft survival afterward, resulting in a clear
      distinction from the nonhypertensive group at around 10 years after
      transplantation. Mean SBP was a significant risk factor for graft survival.
      Hypertension may be a surrogate for a poor renal graft prognosis in the long run.

PMID- 22483456
TI  - Long-term risk of hypertension and chronic kidney disease in living kidney
      donors.
AB  - OBJECTIVE: The aim of this study was to assess the long-term risks of chronic
      kidney disease and arterial hypertension in living kidney donors. METHODS: Donors
      who were followed for more than 1 year after nephrectomy were included. We
      assessed each donor's blood pressure, urine protein, and estimated glomerular
      filtration rate (eGFR). RESULTS: The follow-up rate was 11% (154 out of 1,356
      donors), only 19% of whom were followed by nephrologists. Blood pressure had
      increased from 113/75 to 116/77 mm Hg (P < .01), urinary protein excretion after
      donation did not increase, and renal function was well preserved after donor
      nephrectomy. However, 33 patients (21.4%) showed a decreased eGFR of <60
      mL/min/1.73 m(2), and 3 donors developed end-stage renal disease that required
      renal replacement therapy. CONCLUSIONS: The follow-up rate of living donors after
      donation was low, and we observed an increased risk of developing chronic kidney
      disease after donation.

PMID- 22483457
TI  - Correlation between treated hypertension in prepregnancy and transplanted kidney
      function deterioration during pregnancy even if within pregnancy permission
      criteria.
AB  - Neither pregnancy nor birth is easy in female patients with chronic renal
      failure, but after kidney transplantation, childbirth is possible when the graft
      function is good. There are few guidelines for pregnancy permission and multiple
      reports of decreased transplanted kidney function after pregnancy. In this study,
      we analyzed factors that influenced transplanted kidney function deterioration
      during pregnancy. Twenty-one women among 33 total pregnancies have given birth in
      our institution. Factors analyzed were donor and recipient age at
      transplantation, birth age of recipient, living or cadaveric donor, hemodialysis
      period before transplantation, delivery method, presence of hypertension and
      protein urea at the beginning of pregnancy, and period between pregnancy and
      transplantation. Maternal graft function at the beginning of the pregnancy was
      1.16 +/- 0.39 mg/dL (range = 0.5-2.1). A rise in serum creatinine (S-Cr) before
      delivery was observed in 10/21 cases: six cases showed a rise in S-Cr levels at 1
      or more years after delivery. From the analysis, graft function at the beginning
      of pregnancy became a significant factor correlating with the elevation of S-Cr
      levels during pregnancy (P = .002). Patients were divided into two groups by S-Cr
      levels at the beginning of pregnancy: group A was S-Cr <= 1; group B was S-Cr 1-2
      mg/dL. All group A cases showed stable graft function before and after delivery.
      Some individuals in group B experienced deterioration of graft function during
      pregnancy; the others had stable graft function. The presence of treated
      hypertension at the beginning of pregnancy in group B significantly impacted
      renal dysfunction during pregnancy (P < .05). In conclusion, the presence of
      treated hypertension at the beginning of pregnancy was a significant risk factor
      for functional deterioration of the transplanted kidney during pregnancy even if
      the individual was initially within pregnancy permission criteria.

PMID- 22483458
TI  - Long-term renoprotective effect of candesartan in renal transplant patients.
AB  - BACKGROUND: The renoprotective effects of angiotensin II type 1 receptor blockers
      (ARBs) have been demonstrated in a number of clinical studies, but there are few
      evaluations of long-term ARB treatment. We measured blood pressure, urine
      protein, and estimated glomerular filtration rate (eGFR) among patients under
      long-term (up to 9 years) treatment with candesartan cilexetil to evaluate its
      safety and effectiveness to protect renal graft function. METHODS: This study of
      41 patients (31 male and 10 female) who presented with proteinuria and
      hypertension (blood pressure >140/90 mm Hg) after receiving a renal graft. Their
      serum creatinine level at baseline was 1.51 +/- 0.53 mg/dL. Cyclosporine or
      tacrolimus were concomitantly prescribed for 18 (43.9%) and 22 (53.7%) subjects,
      respectively. The ARB treatment period was >=12 months (up to 9 years, mean 4.8
      years). Combination with other antihypertensive drugs (calcium antagonists) was
      necessary in 14/41 subjects (34.1%). RESULTS: Significant declines in blood
      pressure were observed during the treatment period; blood pressure reduction
      target (blood pressure <130/80 mm Hg) was met in 56.1% for systolic and 68.3% for
      diastolic pressure. No significant increase in serum creatinine level or eGFR was
      observed. Urinary protein was reduced to negative or marginal in 63.4% of the
      subjects, demonstrating a significant decrease. CONCLUSIONS: Candesartan
      cilexetil was considered to be safe even for long-term treatment in renal
      transplant patients, and effective to protect renal graft function.

PMID- 22483459
TI  - Protective effect of paricalcitol on cyclosporine-induced renal injury in rats.
AB  - We evaluated the protective effect of paricalcitol on cyclosporine (CsA)-induced
      renal injury using an experimental model of chronic CsA nephropathy. Paricalcitol
      (50 and 200 ng/kg/d) was concomitantly administered with CsA (15 mg/kg/d) for 28
      days in rats. We assessed the effects of paricalcitol by measuring degree of the
      tubulointerstitial fibrosis (TIF) and inflammation, a profibrotic cytokine
      (betaig-h3), a proapoptotic gene (caspase-3), apoptotic cell death, and oxidative
      stress. The CsA-treated rats showed increased TIF and inflammatory cell
      infiltration, but paricalcitol treatment (200 ng/kg) significantly decreased
      those compared with the CsA-alone group. The expression of betaig-h3, a biologic
      marker of transforming growth factor beta1, which was increased in the CsA group,
      also decreased with paricalcitol treatment. The increased rates of excretion of
      urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and expression of tissue 8-OHdG
      produced by CsA treatment were significantly attenuated by paricalcitol
      treatment. The increased expression of caspase-3 and number of TUNEL-positive
      cells in the CsA group were decreased with concomitant paricalcitol treatment.
      The effect of paricalcitol was more evident high among the rather than low-dose
      cohort. In conclusion, paricalcitol showed antiinflammatory and antifibrotic
      effects. This finding may provide a rationale for use of paricalcitol in CsA
      induced renal injury.

PMID- 22483460
TI  - Fasting long-acting natriuretic peptide correlates inversely with metabolic
      syndrome in kidney transplant patients.
AB  - The metabolic syndrome (MetS) is a risk factor for posttransplant diabetes
      mellitus, chronic graft dysfunction, graft loss, occurrence of atherosclerotic
      events, and patient death among kidney transplantation patients. Long-acting
      natriuretic peptide (LANP) is among the peptide hormones in atrial natriuretic
      peptide prohormone. Low levels of natriuretic peptide may lead to reduced
      lipolysis and excessive weight gain in obese patients. This study was undertaken
      to evaluate the relationship between MetS and fasting serum LANP concentration
      among kidney transplanted patients. Fasting blood samples were obtained from 69
      kidney recipients. The MetS and its components were defined using the diagnostic
      criteria of the International Diabetes Federation. Fasting LANP levels were
      measured using a commercial enzyme immunoassay kit. The prevalence rate of MetS
      was 20.3% (14/69). Fasting LANP level negatively correlated with MetS among these
      patients (P = .010). Using univariate linear regression analysis, serum LANP
      values were negatively correlated with hemoglobin (r = -0.252; P = .037), and
      positively correlated with blood urea nitrogen (r = 0.254; P = .035) and
      creatinine (r = 0.311; P = .009). Multivariate forward stepwise linear regression
      analysis of the significant variables revealed that creatinine (R(2) change =
      0.097; P = .009) was an independent predictor of fasting serum LANP concentration
      among kidney transplanted patients. Serum LANP concentration correlates inversely
      with MetS; for these patients, creatinine is an independent predictor of the
      serum LANP value.

PMID- 22483461
TI  - Clinical manifestations of hypercalcemia and hypophosphatemia after kidney
      transplantation.
AB  - INTRODUCTION: Abnormalities of calcium and phosphorus metabolism in end-stage
      renal disease patients can persist after transplantation. We investigated their
      natural courses after transplantation, their risk factors for posttransplantation
      hypercalcemia and hypophosphatemia, and their impacts on allograft outcomes.
      METHODS: We retrospectively analyzed a total of 490 adult patients who underwent
      kidney transplantations between 2000 and 2009. RESULTS: The serum calcium
      continued to increase, and reaching a plateau at around 3 months after
      transplantation. Thereafter it decreased, reaching a stable level by 2 years.
      Forty-four patients (9.0%) displayed hypercalcemia within 1 year; it persisted
      longer than that in 23 subjects (4.7%). Both longer dialysis duration (odds ratio
      [OR] 1.423; 95% confidence interval [CI], 1.192-1.699) and high intact serum
      parathyroid hormone (iPTH) level before transplantation (OR 1.002; 95% CI, 1.000
      1.003) increased the risk for posttransplantation hypercalcemia. After a
      significant decrease during the first week, the serum phosphorus level increased,
      becoming stable between 1 and 6 months after transplantation. Hypophsphatemia
      occurred in 379 patients (77.3%) with 336 patients displaying hypophosphatemia
      without hypercalcemia. However, neither hypercalcemia nor hypophosphatemia
      influenced graft outcomes. Eight patients underwent pretransplantation
      parathyroidectomy, whereas 4 patients underwent posttransplantation
      parathyroidectomy. Neither group of patients experienced posttransplantation
      hypercalcemia. CONCLUSIONS: Both hypercalcemia and hypophosphatemia are common
      after renal transplantation, especially among patients with a long history of
      dialysis before transplantation. Strict control of hyperparathyroidism including
      parathyroidectomy before transplantation may be the appropriate approach to these
      abnormalities.

PMID- 22483462
TI  - Elevated fibroblast growth factor 23 levels as a cause of early post-renal
      transplantation hypophosphatemia.
AB  - BACKGROUND: Hypophosphatemia is a common complication after renal
      transplantation. Hyperparathyroidism has long been thought to be the cause, but
      hypophosphatemia can persist after high parathyroid hormone (PTH) levels
      normalize. Furthermore, calcitriol levels remain inappropriately low after
      transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast
      growth factor 23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis,
      and accumulates in chronic kidney disease. We performed prospective study to
      investigate if FGF-23 early after renal transplantation contributes to
      hypophosphatemia. METHODS: We measured FGF-23 levels before and at 1, 2, 4, and
      12 weeks after transplantation in 20 renal transplant recipients. Serum
      creatinine, calcium (Ca), phosphate (Pi), intact PTH (PTH), and 1,25-dihydroxy
      vitamin D (1,25(OH)(2)VitD) were measured at the same time. RESULTS: FGF-23
      levels decreased by 97% at 4 weeks after renal transplantation (PRT) (7,471 +/-
      11,746 vs 225 +/- 295 pg/mL; P < .05) but were still above normal. PTH and Pi
      levels also decreased significantly after renal transplantation, and Ca and
      1,25(OH)(2)VitD slightly increased. PRT hypophosphatemia of <2.5 mg/dL developed
      in 15 (75%) and 12 (60%) patients at 4 weeks and 12 weeks respectively. Compared
      with nonhypophosphatemic patients, the levels of FGF-23 of hypophosphatemic
      patients were higher (303 +/- 311 vs 10 +/- 6.9 pg/mL; P = .02) at 4 weeks PRT.
      FGF-23 levels were inversely correlated with Pi (r(2) = 0.406; P = .011); PTH was
      not independently associated with Pi (r(2) = 0.132; P = .151). CONCLUSIONS: FGF
      23 levels decrease dramatically after renal transplantation. During the early PRT
      period, Pi rapidly decreased, suggesting that FGF-23 is cleared by the kidney,
      but residual FGF-23 may contribute to the PRT hypophosphatemia. FGF-23, but not
      PTH levels, was independently associated with PRT hypophosphatemia.

PMID- 22483463
TI  - New-onset diabetes mellitus in cyclosporine-treated organ transplant patients in
      Taiwan: interim analysis (6 months) of postmarketing surveillance.
AB  - Posttransplant new-onset diabetes mellitus (NODM) is an important complication
      among patients receiving immunosuppressants. It has a considerable impact on
      chronic allograft dysfunction. Calcineurin inhibitors have been implicated in the
      development of posttransplant NODM. Since high-risk candidates also undergo
      transplantation, prevention and control of posttransplant NODM is important. A 3
      year postmarketing surveillance study is currently underway in Taiwan to evaluate
      the incidence and risk factors leading to development of NODM among de novo and
      maintenance solid-organ transplant patients receiving cyclosporine (CsA)-based
      immunosuppressive therapy. Concomitant therapy consisted of basiliximab,
      mycophenolate mofetil or enteric-coated mycophenolate sodium, and
      corticosteroids. Diabetes was diagnosed according to the American Diabetes
      Association criteria. This 6-month protocol-defined interim analysis included 101
      patients (84 de novo, 17 maintenance) who received renal (n = 77), liver (n =
      13), or heart (n = 11) transplantation. At the end of 6 months, 8/101 (7.92%)
      patients experienced NODM. The mean time to NODM was 3.05 months. No significant
      difference was observed between NODM and non-NODM patients for risk factors: age,
      body mass index, blood pressure, gender, high-density lipoproteins/triglycerides
      hdl/tg, and anti-hepatitis C virus. The composite endpoint of biopsy-proven acute
      rejection, graft loss, or death was reached in four patients, with a mean time to
      event of 3.81 months. Infections were noted in 34 subjects but, no malignancies.
      Among 389 adverse events reported in 91 patients (90.1%), the majority were of
      mild to moderate severity. Two deaths were reported: heart transplant recipients
      with acute rejection and cytomegalovirus meningitis with respiratory failure.
      Long-term enrollment with follow-up evaluation of these NODM patients up to 3
      years will help evaluate the NODM incidence rates and exact graft survival and
      overall survival rates of CsA-treated transplant patients in Taiwan.

PMID- 22483464
TI  - Gene polymorphisms are associated with posttransplantation diabetes mellitus
      among Taiwanese renal transplant recipients.
AB  - BACKGROUND: Genetic variations may affect posttransplantation metabolic syndrome
      and diabetes mellitus (PTDM), which is associated with greater morbidity and
      progressive impairment of both patient and graft survivals. The aim of this study
      was to evaluate several candidate gene polymorphisms for their association with
      the risk of developing PTDM. METHODS: In April 1999, we enrolled 278 renal
      transplant participants, including 251 subjects free of diabetes and 27 with
      PTDM. We studied several candidate gene polymorphisms associated with diabetes:
      4G/5G polymorphism of plasminogen activator inhibitor 1 (PAI-1) at -675; C/T
      polymorphism of interleukin-1beta (IL-1beta) at -511; G/C polymorphism of IL-6 at
      174; polymorphic XbaI of Glucose transporter 1 (GLUT1); and C/T polymorphism of
      methylenetetrahydrofolate redutase (MTHFR) at 677. RESULTS: The PTDM group had an
      older mean age (47.6 +/- 9.8 years), greater predominance of men (77.8%), higher
      number of chronic diseases (CDN >=2, 96.3%), and more patients using tacrolimus
      based immunosuppression (44.4%; P < .05). Using model A, a simple logistic
      regression, we observed that patients with the IL-6 G/G genotype experienced a
      lower risk of developing PTDM (odds ratio [OR], 0.08; 95% confidence interval
      [CI] 0.01-0.86), and multiple logistic regression models B and C, after adjusting
      for different variables, confirmed this observation (model B: OR, 0.05; 95% CI,
      0.00-0.66). The IL-6 G/G genotype showed a borderline effect in model C (OR,
      0.02; 95% CI, 0.00-1.16). There were no significant differences between the 2
      groups in genotype variations of PAI-1, IL-1beta, GLUT-1, and MTHFR. CONCLUSIONS:
      The G/G genotype of IL-6 may play an important role to lower the risk for PTDM
      development.

PMID- 22483465
TI  - Percentages of water, muscle, and bone decrease and lipid increases in early
      period after successful kidney transplantation: a body composition analysis.
AB  - BACKGROUND: Successful kidney transplantation (KT) can theoretically reconstitute
      body composition of a patient with chronic kidney disease (CKD). However, the
      practical changes have not been well documented. We evaluated changes in body
      composition among candidates before and 1 year after KT. METHODS: We enrolled 37
      male and 18 female kidney recipients eligible for comparison of their body mass
      index (BMI), body composition, and lipid metabolism before and 1 year after KT.
      Twenty-one patients had been induced with a calcineurin inhibitor, mycophenolate
      mofetil, steroid, and basiliximab, and 34 others underwent steroid withdrawal on
      postoperative day 3. The body composition was analyzed using bioelectrical
      impedance. We also analyzed changes in BMI and lipid profiles. RESULTS: There was
      no significant change in BMI (21.4 +/- 3.1 vs 21.7 +/- 3.5 kg/m(2)). Regarding
      body composition, the water level decreased significantly (61.2 +/- 4.9% vs 58.3
      +/- 5.3%; P < .05). In contrast, fat significantly increased (16.4 +/- 6.7% vs
      20.3 +/- 7.1%; P < .05). More interestingly, successful KT significantly
      decreased the muscle and bone mass at 1 year after KT (37.3 +/- 5.1% vs 34.8 +/-
      4.7%; 16.3 +/- 2.1% vs 15.2 +/- 2.1%; respectively; P < .05). Serum lipid
      profiles of total cholesterol, low-density lipoprotein cholesterol, and
      triglyceride worsened after KT. Comparing the 2 protocols, there was no
      difference in any item. CONCLUSIONS: Care must be taken even after successful KT
      to avoid dyslipidemia, which is a risk factor for cardiovascular disease. Well
      programmed dietary and/or exercise protocols to prevent muscle atrophy and fat
      gain should be considered even after successful KT.

PMID- 22483466
TI  - Serum adiponectin levels in renal transplant recipients with and without
      metabolic syndrome.
AB  - OBJECTIVES: Adiponectin (APN) is an adipocyte-derived protein that has anti
      inflammatory, anti-atherogenic, and insulin-sensitizing effects. Lower serum APN
      level is associated with various inflammatory and metabolic diseases in the
      general population. Kidney transplant (KT) recipients are at higher risk for
      developing several metabolic disorders, including metabolic syndrome (MS). The
      aim of the current study was to assess the change of APN level in KT recipients
      with and without MS. METHODS: Prevalent KT recipients followed at our hospital
      were enrolled for the cross-sectional study of MS. The modified Adult Treatment
      Panel III criteria adopted for the Asian population were used to define MS.
      Overnight fasting blood samples were obtained for biochemistry and APN. APN was
      assayed with a commercially available enzyme-linked immunosorbent assay (ELISA)
      kit. The simplified Modification of Diet in Renal Disease (MDRD) equation was
      used for the calculation of estimated glomerular filtration rate (eGFR).
      Univariate and multivariate logistic regression were performed to determine
      parameters that were associated with serum APN level. RESULTS: A total of 271 KT
      recipients (male:female = 133:138), with a mean age of 52.3 +/- 12.6 years, were
      enrolled for the study of MS. The mean duration of follow-up posttransplantation
      was 9.02 +/- 5.91 years. MS was found in 72 of 271 KT recipients (26.6%).
      Patients with MS were older, had significantly higher body weight, waist
      circumference, serum creatinine, fasting plasma sugar, and hemoglobin A1c, but
      lower serum APN level and eGFR than did patients without MS. Univariate logistic
      regression revealed the following variables were associated with APN level: MS,
      gender, body weight, body height, waist circumference, body mass index, serum
      creatinine, fasting blood sugar, triglyceride, high-density lipoprotein (HDL)
      cholesterol, and eGFR. Multivariate analysis revealed that gender, body weight,
      serum creatinine, triglyceride, and HDL cholesterol were associated with APN
      level. CONCLUSION: Our results revealed that KT recipients with MS had
      significantly lower serum APN levels, even in the presence of lower eGFR, than
      those without MS.

PMID- 22483467
TI  - Clinical outcomes of recipients with aplastic bone disease after renal
      transplantation.
AB  - OBJECTIVES: We expect that if chronic renal failure (CRF) is improved after renal
      transplantation (RTx), dialysis osteopathy bone lesions would also recover to
      normal. Nevertheless, it is controversial whether bone lesions really improve
      after RTx. In this study, we evaluated whether pathological dialysis osteopathy
      improved after RTx. MATERIALS AND METHODS: The 84 patients who had undergone
      living related RTx had also undergone a bone biopsy (Bx) since January 2004,
      including 13 (16.0%) with a diagnosis of aplastic osteopathy. They included 7 men
      and 6 women. The average hemodialysis (HD) period was 40.3 months. The
      immunosuppression was tacrolimus (FK); mycophenalate mofetil (MMF) and steroid.
      We examined Ca, P, intact-PTH (i-PTH), metabolic bone markers, and bone density
      (DXA) before and 1 year after RTx. In addition, a Bx was performed after having
      osteal labeling twice before Bx. In addition 2 cases (15.3%) also underwent a Bx
      after RTx. RESULTS: All cases survive with well functioning renal grafts. The
      mean levels of Ca and P before RTx were 8.7 mg/mL and 6.6 mg/dL, respectively.
      The mean i-PTH level was 137.8 pg/mL before RTx and of alkaline phosphatase (ALP)
      was 202.1 U/L before RTx. The total density and % age match of DXA before RTx
      averaged 398.7 mg/ccm and 96.7%, respectively. The mean bone volume fraction
      (BV/TV: Bone Volume/Tissue Volume) before RTx was 17.2%. The mean osteoid volume
      (OV/TV) before RTx was 2.7%. The mean fibrosis volume (Fb.V/TV) before RTx was
      0%. The mean bone formation rate (BFR/BV) before RTx was 2.1 %/y. Two cases were
      also pathologically diagnosed as renal osteodystrophy at 1 year after RTx: 1 case
      was mixed type, and another was osteomalacia, which was accompanied by a lumbar
      compression fracture (Fx) during the clinical course. CONCLUSIONS: Bone
      metabolism in patients with aplastic ROD histologically improved at 1 year after
      RTx, presumably due to good renal transplant function. However, it is unknown
      whether both hypophosphatemia and decrease of FGF-23 improved bone However,
      patients with aplastic ROD were not completely normalized histologically at 1
      year after RTx.

PMID- 22483468
TI  - Successful kidney transplantation ameliorates arterial stiffness in end-stage
      renal disease patients.
AB  - PURPOSE: Successful kidney transplantation (KTx) can ameliorate bodily damage
      caused by end-stage renal disease (ESRD). Arterial stiffness (AS) is one of the
      critical factors that shorten the survival of patients due to cardiovascular
      events. KTx may reduce AS as well; however, this has not been investigated well.
      We therefore conducted a retrospective study using noninvasive pulse wave
      velocity (PWV), which is a useful index of aortic damage. PATIENTS AND METHODS:
      Fifty-eight consecutive kidney recipients (34 men, 24 women) were enrolled in
      this study. Mean age at transplantation was 40.5 +/- 12.3 years and the dialysis
      period was 73.1 +/- 95.8 months. The brachial-ankle PWV was measured
      preoperatively and 6 months postoperatively. First, we investigated the
      relationship between the PWV and the other parameters related to AS. Second, we
      studied the pre- to posttransplant change in PWV to evaluate the amelioration of
      AS after successful KTx. RESULTS: PWV showed significant positive correlations
      with age, systolic blood pressure (BP), diastolic BP, and abdominal aortic
      calcification index. After successful KTx, PWV significantly decreased (P < .01).
      In addition, systolic and diastolic BP significantly decreased (P < .01 and P <
      .05, respectively). CONCLUSION: Successful KTx ameliorates AS in ESRD patients.
      This might explain the improved cardiovascular prognosis of ESRD patients who
      undergo KTx.

PMID- 22483469
TI  - Coronary artery calcification in kidney transplant recipients with long-term
      follow-up.
AB  - OBJECTIVES: Kidney transplantation (KT) is associated with increased incidence of
      hypertension, hyperlipidemia, metabolic syndrome, and posttransplant diabetes
      mellitus that promote the development of coronary artery calcification (CAC). The
      aim of the current study was to elucidate the extent of CAC and its risk factors
      among KT patients. METHODS: A cross-sectional study was performed to evaluate the
      severity of CAC in our KT patients. Multidetector computed tomography was
      performed to assess the coronary artery calcium score (CACS). Patients were
      further stratified according to the CACS as: group 1: 0-10, group 2: 11-100,
      group 3: 101-300, group 4: 301-1000, and group 5: >1000. Clinical as well as
      demographic data were compared among groups. Linear regression analysis was
      performed to determine factors that were associated with CAC. RESULTS: A total of
      99 patients were enrolled in the study. The mean age was 53.5 +/- 11.8 years and
      duration of follow-up post-KT was 11.2 +/- 5.9 years. The distribution of CACS in
      groups 1 through 5 was: 41.4%, 20.2%, 11.1%, 15.2%, and 12.1%, respectively. A
      significantly higher CACS was found in males, patients with pretransplant
      diabetes mellitus, older current age, older age at KT, hypertension, higher body
      weight, higher fasting plasma sugar level and lower high-density lipoprotein
      (HDL) cholesterol. Twenty-nine (29.3%) patients fulfilled criteria for metabolic
      syndrome (MS). The CACS was significantly higher in patients with MS than in
      those without MS. An incremental CACS was found to be correlated with increasing
      number of MS components (P = .003). Multivariate linear regression revealed that
      female gender, current age, hypertension, and HDL cholesterol were associated
      with CAC. CONCLUSION: KT was associated with high CACS in a significant
      proportion of patients with long-term follow-up. Several risk factors were
      identified. Some of them were potentially treatable and should be taken into
      consideration in the management of KT recipients.

PMID- 22483470
TI  - Clinical usefulness of 3-dimensional computerized tomographic renal angiography
      to detect transplant renal artery stenosis.
AB  - OBJECTIVE: The aim of this study was to evaluate whether 3-dimensional
      computerized tomographic angiography (3D-CTA) is useful to detect transplant
      renal artery stenosis (TRAS). METHODS: Fourteen patients with clinically
      suspected TRAS underwent color Doppler ultrasonography (CDU) and 3D-CTA before
      renal angiography. We compared 3D-CTA and CDU for accuracy based on the results
      of renal angiography. The safety of 3D-CTA was investigated by measuring the
      estimated glomerular filtration rate (eGFR) before and after the 3D-CTA
      examination. RESULTS: The 10 men and 4 women who participated in this study
      showed a mean eGFR of 75 mL/min/1.73 m(2) (range 60-94). Of these, 9 patients
      were diagnosed with TRAS. 3D-CTA detected stenoses in all 9 patients, but CDU
      failed to detect it in 3, including, 2 with end-to-side arterial anastomoses,
      which may be more challenging to detect compared with end-to-end anastomoses. The
      stenotic area in 3D-CTA was similar to that detected by renal angiography (70 +/-
      12 vs 68 +/- 11). The eGFR did not differ significantly before versus after the
      3D-CTA examination; 72 +/- 13 vs 69 +/- 14 mL/min/1.73 m(2). CONCLUSIONS: 3D-CTA
      was an effective safe method to detect renal artery stenosis among transplant
      recipients with an eGFR >60 mL/min/1.73 m(2).

PMID- 22483471
TI  - Cytomegalovirus disease in kidney transplant recipients: incidence, clinical
      profile, and risk factors.
AB  - BACKGROUND: Cytomegalovirus (CMV) is one of the most frequently encountered
      opportunistic viral pathogens in renal transplantation. Approximately 60% of
      transplant recipients will have CMV infection and >20% will develop symptomatic
      disease. With the advancement of immunosuppression, variation in the occurrence
      and pattern of infections is possible. We described the incidence, clinical
      profile, outcome, and risk factors for development of CMV disease among renal
      transplant recipients. PATIENTS AND METHODS: We studied patients who underwent
      transplantation from January 2005-December 2009 admitted for CMV disease. CMV
      infection was present if the patient had at least 1 of the following: positive
      early antigen detection in blood or tissues, positive CMV antigenemia, or a 4
      fold increase in pretransplantation CMV antibody titer. CMV disease was diagnosed
      if CMV infection was accompanied by clinical signs and symptoms. Descriptive
      statistics included measures of central tendency for continuous numerical
      variables and percentage-frequency distribution for categorical variables z test,
      Wilcoxon-Mann-Whitney test, and Fisher exact test were used to determine risk
      factors for CMV disease. RESULTS: About 1502 renal transplantations were done
      during the study period with mean follow-up of 33.8 months. CMV disease was
      confirmed in 85 (5.8%) recipients who developed 88 CMV disease episodes. Of the
      85 patients who had CMV disease, 55% developed <= 3 months posttransplantation.
      Fever was the most common presenting symptom, 53% had coinfection, and case
      fatality rate was 11%. Risk factors that were statistically significant in the
      development of CMV disease were as follows: recipient/donor relationship (P =
      .0115), CMV donor+/recipient- (P = .004), and recent rejection treatment (P =
      .0084). CONCLUSION: Incidence of CMV disease was 5.8% with fever as the most
      common presenting symptom and 55% developed CMV disease <= 3 months
      posttransplantation. Coinfection occurred in 53% and case fatality rate in 11%.
      Risk factors for developing CMV disease included CMV donor+/recipient- and recent
      acute rejection treatment.

PMID- 22483472
TI  - Cytomegalovirus viremia after kidney transplantation in Thailand: predictors of
      symptomatic infection and outcome.
AB  - BACKGROUND: While prevention of cytomegalovirus (CMV) infection after kidney
      transplantation (KT) has become a standard practice in Western countries, this
      approach is not always feasible in Thailand. In order to argue for the need for
      CMV prevention, the knowledge on the incidence and impact of the CMV infection
      following KT is highly desirable. METHODS: We retrospectively reviewed medical
      records of adult patients who underwent KT at our transplant center between
      January 2006 and December 2010. Patients who developed CMV viremia within 1 year
      after transplantation were studied for the incidence, risk factors, and outcome
      of symptomatic infection. The threshold value of blood CMV DNA load indicating
      symptomatic infection was also analyzed. RESULTS: Symptomatic CMV infection
      occurred in 18 (4.6%) patients within a median time of 12.1 (range, 3-30) weeks
      after KT. At initial presentation, coexisting opportunistic infection was common
      (44%) and gastrointestinal tract was the major type of organ involvement (44%).
      Between groups of patients with symptomatic and asymptomatic CMV infection, the
      mean (+/- standard deviation) level of blood viral load were significantly higher
      in the first group [4.2 (+/- 0.5) vs 3.3 (+/- 0.4) log copies/mL]. From
      multivariate analysis, associated factors of symptomatic infection included acute
      rejection [odds ratio (OR) 7.32, P = 0.001], and acute tubular necrosis (OR 3.44,
      P = .019). Death (13%) and graft failure (13%) were significantly higher among
      the symptomatic infection group than those in the no-infection group (P = .005
      and .03, respectively). CONCLUSION: Despite a low incidence rate, symptomatic CMV
      infection clearly resulted in significant morbidity following KT. In Thailand,
      the prevention of CMV infection should be prioritized among high-risk KT
      populations.

PMID- 22483473
TI  - Post-renal transplant cytomegalovirus infection: study of risk factors.
AB  - OBJECTIVES: Cytomegalovirus (CMV) is a common opportunistic infection following
      renal transplantation (RTx). It responds promptly to antiviral treatment. The
      mortality rate reaches 90% if untreated. Identification of risk factors helps in
      the early diagnosis of CMV. We studied demographic features, risk factors, and
      outcomes associated with CMV infection in RTx recipients despite ganciclovir
      prophylaxis. MATERIALS AND METHODS: We reviewed 720 RTx recipients between 2007
      and 2009. We examined the serostatus of the donor and recipient before
      transplantation using an enzyme-linked immunosorbent assay, and diagnosed CMV
      infections in recipients by CMV DNA detection with a polymerase chain reaction.
      RESULTS: A total of 42 of 750 (5.6%) patients were identified to display CMV
      infection (69.1%) or disease (30.9%). Their mean age was 34 +/- 13.5 years, with
      80.9% men. CMV serologic status was D+/R- in 21.4% and D+/R+ in 59.5% patients.
      Fever, malaise (76.2%), and leukopenia (52.3%) were the commonest presenting
      symptoms; diabetes (30.9%) and hepatitis C virus (28.6%) the commonest comorbid
      conditions. Risk factors were triple drug immunosuppression (47.6%),
      antithymocyte globulin ATG induction (54.8%), and a rejection episode (26.1%) and
      methylprednisolone (76.2%) which were more common in CMV disease than infection.
      Mean CMV DNA at diagnosis was 78,803; 71.2% patients developed CMV within 6
      months posttransplantation, the majority occurring after 3 months. With a mean
      follow-up of 4 +/- 1.9 years, patient and graft survival rates were 85.7% and 81%
      with a mean serum creatinine value of 1.83 +/- 12 mg/dL. CONCLUSIONS: Universal
      CMV prophylaxis was associated with a low incidence (5.6%) and mild form of CMV
      disease among our patients.

PMID- 22483474
TI  - Historical comparison of prophylactic ganciclovir for gastrointestinal
      cytomegalovirus infection in kidney transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) can cause morbidity in kidney transplant
      recipients. The gastrointestinal (GI) tract is a major target for CMV disease.
      The aim of this study was to evaluate the benefit of ganciclovir prophylaxis on
      GI CMV infection in intermediate-risk CMV seropositive transplant recipients.
      METHODS: Since January 2009, intravenous ganciclovir (5 mg/kg, twice daily) was
      administered for 14 days after kidney transplantation in 41 patients. The
      historical control group consisted of 45 patients who received kidney
      transplantations between January 2007 and December 2008. To evaluate the effects
      of prophylaxis on GI CMV infection, we performed routine endoscopic examinations
      with mucosal biopsies at the time of transplantation as well as 1, 3, and 6
      months thereafter. RESULTS: The average age of the 86 studied patients was 43.7
      +/- 10.6 years (range = 14-63) and the male-to-female ratio 1:1.3. Forty-three
      (50%) patients underwent deceased donor transplantations and 84 (97.7%) patients
      were CMV seropositive at that time. The incidence of GI CMV infection was
      significantly lower among the prophylaxis than the historical control group
      (24.4% vs 48.9%, P = .026). Patient age, numbers of deceased donors, and
      tacrolimus trough levels at 1 and 3 months posttransplant were significantly
      lower in the prophylaxis than the historical control group. Logistic regression
      analysis revealed ganciclovir prophylaxis to be the only significant risk factor
      for GI CMV infection. CONCLUSION: Prophylactic treatment with ganciclovir
      decreased the incidence GI CMV infection among seropositive kidney transplant
      recipients.

PMID- 22483475
TI  - Spectrum of cytomegalovirus-induced renal pathology in renal allograft
      recipients.
AB  - Viral infections in renal allograft recipients constitute an important cause of
      renal graft dysfunction. They have shown an increasing incidence coinciding with
      more potent immunosuppression regimens. Cytomegalovirus (CMV) is well-known cause
      of a tubulointerstitial nephritis rich in plasma cells with cytopathic changes in
      tubular epithelial and endothelial cells. However, involvement of glomeruli and
      larger arteries in the absence of tubulointerstitial disease is rare. In this
      study, we demonstrated the spectrum of renal disease caused by CMV among renal
      allograft recipients. Retrospective analysis of 2900 renal allograft biopsies
      performed over a 10-year period revealed 10 cases of CMV infection, with half of
      them (5/10) detected in 2010-2011. Although tubulointerstitial nephritis due to
      CMV was the most common lesion (7/10), we noted an increased incidence of CMV
      glomerulopathy with (1/10) or without (3/10) coexisting tubulointerstitial CMV
      disease. Isolated glomerular involvement was characterized by a relative lack of
      inflammation in any of the compartments along with the presence of cytopathic
      changes in the glomerular endothelial cells and podocytes. Another patient had
      CMV-induced thrombotic microangiopathy. The coexistent diseases were calcineurin
      inhibitor toxicity (n = 1), antibody-mediated rejection (n = 1), cellular
      rejection (n = 2), and invasive fungal infection (n = 1). In conclusion, there is
      a wide spectrum of CMV-induced lesions. CMV glomerulopathy is characterized by
      cytopathic changes in glomerular endothelial cells and podocytes with a lack of
      significant inflammation. In contrast, CMV-induced arteriopathy can present as
      thrombotic microangiopathy. Coinfection with other pathogens like invasive fungi
      can lead to graft failure.

PMID- 22483476
TI  - Dual positivity of donor and recipient plasma for BK virus confers a high risk
      for development of bk nephropathy in renal allograft.
AB  - BACKGROUND: BK nephropathy (BKN) is an important complication of renal
      transplantation, with a reported incidence between 1% and 10% in different parts
      of the world. Known risk factors for the development of BKN are the recently
      introduced immunosuppressants and steroids. However, the preexisting viral load
      may add to the risk for development of BKN. Therefore, the present study was
      designed to monitor the baseline BK virus (BKV) DNA in renal transplant donors
      and recipients in India for correlation with the development of BKN. METHODS:
      This study used real-time polymerase chain reaction (PCR) for quantification of
      BKV DNA in the plasma of kidney transplant donors (n = 38) and recipients (n =
      87) at the time of surgery. The control BKV DNA was manufactured from a known
      positive human sample, by cloning a 133-bp PCR product of bases 4,329 to 4,462 of
      the large T-antigen (TAg) of BKV in a plasmid vector. RESULTS: Twenty-five of 87
      recipient (28.7%) and 17/38 donor (44.7%) plasma samples were positive for BKV
      DNA at the time of transplantation with a median viral load of 910 (range 49
      4770) and 312 (range 79-1508) copies per mL plasma, respectively. Six of 38 donor
      recipient pairs showed viremia in both the recipient and donor: 1 developed
      histologically proven BKN at 18 months, 1 showed positive immunohistochemistry
      for SV40 TAg, and 2 others had high levels of viremia (14,545 copies at 6 and
      2,617,524 copies at 3 months). None of the other 81 recipients showed evidence of
      BKN in the follow-up period. CONCLUSIONS: This study showed that 28% of
      recipients and 44% of donors displayed baseline positivity for BKV DNA in plasma,
      which is higher than the reported incidence in the West. The baseline levels of
      BKV DNA in recipients with end-stage renal disease were higher than in donors.
      Dual positivity for BKV DNA in the plasma of donor-recipient pairs conferred a
      high risk of development of BK nephropathy in the allografted kidney.

PMID- 22483477
TI  - Experience of fibrosing cholestatic hepatitis with hepatitis C virus in kidney
      transplant recipients.
AB  - BACKGROUND: Fibrosing cholestatic hepatitis C (FCH-C) is a rare entity that
      occurs among immune-compromised patients resulting from the direct hepatotoxicity
      of a high intracellular viral load along with an ineffective immune system
      ultimately leading to a fatal outcome. We have describes herein 4 renal
      transplant recipients who were diagnosed with FCH-C at our institution in the
      last 8 months. METHODS: Four renal transplant recipients presented with jaundice
      and deteriorating liver function tests. They were diagnosed to display FCH-C
      based on the presence of hepatitis C virus (HCV) RNA and characteristic liver
      biopsy findings; there was no evidence of any other cause of cholestasis or
      biliary obstruction. RESULTS: The patients were men of ages 40, 25, 20, and 27
      years. The durations after transplantation were 1.5, 10, 1.5 and 2.0 years,
      respectively. In all cases pretransplantation screening was negative for HCV
      antibody, HCV RNA, and hepatitis B surface antigen (HBsAg). All 4 patients were
      infected with genotype 1, whereas case 2 had coinfection with type 3. Cases 1 and
      2 who were treated with interferon and ribavirin, showed improvement in
      cholestasis but did not achieve a rapid virological response. Case 1 developed
      graft dysfunction secondary to acute cellular rejection at 4 months after
      initiation of interferon treatment, which was treated with pulse steroids.
      Interferon-based therapy was stopped prematurely in both cases due to
      pancytopenia. Case 3 developed florid pyelonephritis and died without receiving
      therapy for hepatitis C. Case 4 was managed conservatively by decreasing the
      immunosuppression with regular monitoring. CONCLUSION: FCH-C is difficult to
      treat and shows high morbidity and mortality rates. Treatment is associated with
      a risk of graft rejection.

PMID- 22483478
TI  - Hepatic stellate cells attenuate the immune response in renal transplant
      recipients with chronic hepatitis.
AB  - BACKGROUND: Chronic viral hepatitis is no longer a contraindication to renal
      transplantation (RT), owing to our better understanding of the hepatitis virus.
      Hepatitis patients may receive RT depending on their response to viral therapy.
      RT patients with hepatitis generally do not have an inferior prognosis compared
      with RT patients without the disease. Hepatic stellate cells (HSCs) are activated
      during chronic viral hepatitis. The role of HSCs in immunoregulatory effects in
      RT recipients has not been fully elucidated. METHODS: We recruited 22 RT
      recipients with chronic viral hepatitis, who composed the chronic liver disease
      (CLD) group, and 25 disease-free recipients, who served as the control group. We
      retrieved their clinical data and collected serum to measure cytokine levels. To
      investigate the immunoregulatory effect of HSCs, we cocultured HSCs with
      allogeneic antigen-presenting cell-activated T cells (mixed lymphocyte reaction
      [MLR]) in Transwell plates. RESULTS: The liver biopsy disclosed activation HSCs
      in 1 chronic hepatitis C virus recipient without treatment. Serum monocyte
      chemoattractant protein-1 (MCP-1) levels in the CLD group (41.6 +/- 27.4 pg/mL)
      were significantly higher than those in the control group (28.1 +/- 12.8 pg/mL; P
      = .008). There were similar levels of transforming growth factor-beta1 (TGF
      beta1). In allogeneic MLR, HSCs inhibited T-cell activation through the soluble
      factors in the Transwell assays. There was a high level of MCP-1 in the
      supernates of the HSC group in the allogeneic MLR, but TGF-beta1 was lower in
      HSCs cocultured with MLR than in the control group, except in the early period.
      CONCLUSIONS: HSCs may play an immunoregulatory role in chronic viral hepatitis
      recipients to minimize the effect of immunosuppressants without affecting
      rejection. The immunomodulatory effects may be attributed to soluble factors in
      HSCs.

PMID- 22483479
TI  - Safety and efficacy of a quinolone-based regimen for treatment of tuberculosis in
      renal transplant recipients.
AB  - BACKGROUND: Rifampin (RFP) is a first-line antituberculosis drug, but it
      increases the risk of acute rejection (AR) in transplant recipients. This study
      evaluated whether quinolone (QNL) can replace RFP in renal transplant recipients
      with tuberculosis. METHODS: One hundred nine patients with active tuberculosis
      were included. Patients consisted of RFP (n = 91) and QNL (n = 18) groups based
      on the initial treatment regimen. Patients with RFP-associated adverse effects
      were subdivided into RFP-maintenance (RFP-M; n = 18) and QNL-conversion (QNL-C; n
      = 8) groups. Clinical outcomes were compared between groups. RESULTS: The
      incidence of AR was higher in the RFP group than in the QNL group (24.2% vs
      5.6%). The QNL group showed significantly higher 10-year graft survival rates
      than the RFP group (88.1% vs 66.5%; P = .022). The QNL-C group showed
      significantly higher 10-year graft survival rates than the RFP-M group (87.5% vs
      27.8%; P = .011). The rate of complete functional recovery after AR was higher in
      the QNL-C group than in the RFP-M group (50% vs 22.2%). CONCLUSIONS: A QNL-based
      regimen may be safe and effective for treatment of tuberculosis and may lower the
      risk of graft failure in renal transplant recipients.

PMID- 22483480
TI  - High incidence of bacteriuria in early post-kidney transplantation; results from
      a randomized controlled study.
AB  - Since the incidence of bacteriuria in kidney transplant recipients varyes
      according to the study, we examined it among our cases. Our post hoc analysis of
      data from a single-center, parallel, randomized, controlled, open label study
      included 90 patients who underwent kidney transplantation at our hospital from
      April 2010 to January 2011. Patients were randomized to early ureteric stent
      removal at 8 days versus routine ureteric stent removal at 15 days after kidney
      transplantation. We identified the incidence of and causative organism for
      bacteriuria in the early posttransplant period. Seventy-Four patients (58% living
      donors) participated in this study. The overall incidence of bacteriuria was
      56.7% during the first month after kidney transplantation. In patients who had
      bacteriuria, 48% showed symptomatic urinary tract infection, 40% asymptomatic
      bacteriuria and 12% urosepsis. The most common organism was Escherichia coli
      (40%) follow by Klebsiella pneumoniae (19%). The incidence of an ESBL producing
      organism was 34%. The incidence of bacteriuria was high during the early post
      kidney transplant period, requiring increased awareness and surveillance.

PMID- 22483481
TI  - Impact of early ureteric stent removal and cost-benefit analysis in kidney
      transplant recipients: results of a randomized controlled study.
AB  - INTRODUCTION: Duration of retaining ureteric stent in kidney transplantation is
      still controversial. Our study aimed to compare healthcare expenditures in kidney
      transplant recipients with early or routine ureteric stent removal. METHODS: This
      study was a post hoc analysis of data from a single-center parallel randomized
      controlled open-label study. Ninety patients who underwent kidney transplantation
      at a university-based hospital in Thailand from April 2010 to January 2011 were
      enrolled. Patients were randomized to early ureteric stent removal (8 days) or
      routine ureteric stent removal (15 days) after kidney transplantation. The costs
      of direct health care associated with kidney transplantation, urologic
      complication, and urinary tract infection (UTI) within the postoperative period
      among the 2 groups were compared. RESULTS: Seventy-four patients (58% living
      donor) fulfilled the randomized criteria (early removal, n = 37; routine removal,
      n = 37). By intention-to-treat analysis, incidence of UTI in early stent removal
      was less than the routine stent removal group (15/37, 40.5% vs 27/37, 72.9%; P =
      .004). Urologic complication showed no significant difference between the early
      and routine groups (4/37 vs 2/37; P = .39). The cost-benefit analysis of early
      over routine stent removal was 2390 United States dollars (USD) per patient
      (11,182 vs 8792 USD). Presence of UTI significantly increase the hospitalization
      cost of 5131 USD per patient (mean cost = 12,209 vs 7078 USD; P < .001).
      CONCLUSION: UTI in the early post-kidney transplantation period increases
      healthcare cost. Early ureteric stent removal can reduce UTI and reduce
      hospitalization cost. This approach shows cost-benefit in the early management of
      kidney transplant recipients.

PMID- 22483482
TI  - Hormonal differences between female kidney transplant recipients and healthy
      women with the same gynecologic conditions.
AB  - BACKGROUND: End-stage renal disease is associated with severe abnormalities in
      reproductive function. However, the abnormalities are reversed by successful
      kidney transplantation. The aim of the present study was to compare hormonal
      levels between recipients with successful kidney transplantations and healthy
      women with the same gynecologic conditions. METHODS: The study group consisted of
      31 women of reproductive age with end-stage renal disease who underwent
      successful kidney transplantation. The ratio of the control group, composed of
      healthy woman, to the study group was 3:1 matched for age and symptoms. RESULTS:
      Abnormal bleeding (n = 14) and infertility were the most common gynecologic
      conditions in kidney transplant recipients. The levels of estrogen (E2) and
      follicle-stimulating hormone (FSH) in the study group were higher than in the
      control group, but the levels of progesterone (P4) and luteinizing hormone (LH)
      were lower in the study group than in the control group. There were no
      significant differences in prolactin and thyroid-stimulating hormone between the
      two groups. The incidence of infertility in patients who receive steroid was
      higher than those with no steroid use (P = .007). CONCLUSIONS: Compared with
      healthy age- and symptom-matched women, female kidney transplant recipients have
      increased levels of E2 and FSH and decreased levels of P4 and LH. These
      differences in hormone profiles may predispose kidney transplant recipients to
      increased risk of gynecologic pathologies.

PMID- 22483483
TI  - Urothelial cancer after renal transplantation: an update.
AB  - According to the Australian and New Zealand Dialysis and Transplantation
      (ANZDATA) 2010 Annual Report, cancer is surpassing cardiovascular diseases as the
      leading cause of posttransplantation death. Skin cancer and posttransplantation
      lymphoproliferative disorder (PTLD) are 2 cancers in Western countries. However,
      urothelial cancer happens much more frequently among Chinese people. We reviewed
      our experience in Congress of the Asian Society of Transplantation (CAST) 2005,
      including 10 urothelial cancers, among 620 renal transplant recipients. In this
      report, we have presented our updated data. From July 1981 to May 2011, we
      performed 770 renal transplantations followed by graft and native kidney
      sonography annually even among asymptomatic cases using the protocol described in
      CAST 2005. During this period, 35 urothelial tumors were detected, ie, 25 new
      cases were identified in 6 years. These 35 cases included 7 cases with bilateral
      upper tract involvement and 5 of them with bladder tumors. Seven patients had
      bladder cancer alone. In 19 patients, 22 ureteral cancers included 1 that grew
      from the graft ureter, 17 (77.3%) patients showed hydronephrosis by sonography.
      We performed 13 bilateral nephroureterectomies; 2 were known to have bilateral
      upper tract cancer. Four of the other 11 were found to have insidious tumors. In
      contrast, 2 of the 15 initial unilateral nephroureterectomy patients underwent a
      subsequent contralateral nephroureterectomy due to a tumor. The pattern of
      urethral cancer in renal transplant recipients is thoroughly different, including
      female predominance, and a higher incidence of upper tract involvement. We
      emphasize the necessity of routine periodic sonographic survey even among
      asymptomatic patients for early detection of a urothelial tumor.

PMID- 22483484
TI  - Awareness of memory impairment increases the adherence to immunosuppressants in
      kidney transplant recipients.
AB  - OBJECTIVES: Nonadherence to immunosuppressive drugs is a concern among kidney
      transplantation recipients (KTRs). The adverse effects of immunosuppressive drugs
      can trigger nonadherence and lead to a great impact on the allograft survival.
      The aim of this prospective controlled study is to determine the major adverse
      effects of immunosuppressive drugs and their correlation with the nonadherence in
      kidney transplantation recipients. METHODS: All data were collected from medical
      and pharmacy records. We use modified Immunosuppressant Therapy Adherence Scale
      combined with Modified Transplant Symptom Occurrence and Symptom Distress scale
      to explore the relationship between symptom experience related to side effects of
      immunosuppressants and adherence. The risk of nonadherence was estimated by
      stepwise logistic regression while controlling for age, gender, education, and
      immunosuppressive medications. Multivariable analysis was performed using a
      single random effect of P < .2. RESULTS: In total, 412 KTRs completed the
      structured self-report instrument. The weekly pill counts were 84.2 +/- 39.8.
      Overall, 21.4% of patients were nonadherent to immunosuppressive drugs. The most
      common adverse effects of immunosuppressive drugs were memory impairment (28.4%),
      insomnia (26.0%), gastrointestinal discomfort (21.4%), easy fatigue (22.1%), hand
      tremor (23.8%), and vision variation (29.1%). Multivariate analysis revealed that
      the adherence increased in patients with awareness of memory impairment (odds
      ratio 2.320, 95% confidence interval: 1.259-4.274, P = .007). There was no
      significant difference in the incidence of acute rejection, gender, age, and
      education between adherent and nonadherent patients. CONCLUSION: In summary,
      these results indicate a significant prevalence of nonadherence to
      immunosuppressive drugs in kidney transplantation recipients. Awareness of memory
      impairment significantly affected adherence to immunosuppressive drugs.

PMID- 22483485
TI  - Role of plasmapheresis as liver support for early graft dysfunction following
      adult living donor liver transplantation.
AB  - BACKGROUND: Severe early graft dysfunction has been occasionally encountered
      following adult living donor liver transplantation (LDLT). We have assessed the
      effectiveness of plasmapheresis (PP) as liver support for LDLT recipients with
      severe early graft dysfunction. METHODS: Of the 789 adult LDLTs performed between
      January 2007 and December 2009, 50 patients (6.3%) underwent PP as a supportive
      measure during the first month. RESULTS: The mean time from LDLT to start of
      plasmapheresis was 11.2 +/- 6.8 days (range 2-28). The 50 patients underwent 517
      sessions of PP, or a mean of 10.3 +/- 6.8 sessions per patient, over a mean 21.6
      +/- 9.4 days. Thirty-four patients (68%) required concurrent hemodiafiltration.
      Mean serum total bilirubin concentration before PP was 16.2 +/- 6.7 mg/dL,
      peaking at 20.3 +/- 7.9 mg/dL during PP, and decreasing to 13.4 +/- 5.4 mg/dL 1
      week after completion of PP (P < .001 compared with before PP). Except for
      prothrombin time, no other biochemical parameter was significantly altered by PP.
      There were no serious complications related to PP. Of the 50 patients, 17 (34%)
      died soon or a few months after PP. The 6-month graft survival rate after
      completion of PP was 66%; the overall 1-year patient survival rate was 64.0%.
      CONCLUSION: PP appeared to have beneficial effects for LDLT recipients with
      severe early graft dysfunction, namely total bilirubin concentrations greater
      than 10 mg/dL.

PMID- 22483486
TI  - Predictive factors for persistent splenomegaly and hypersplenism after adult
      living donor liver transplantation.
AB  - PURPOSE: The aim of this study was to evaluate predictive factors for persistent
      splenomegaly and hypersplenism after living donor liver transplantation (LDLT).
      PATIENTS AND METHODS: From January 2008 to June 2010, 159 adult patients (116
      males and 43 females) who underwent living donor liver transplantation (LDLT) had
      pre- and post-LDLT computed tomography angiography and survived more than 6
      months. Patients with post-LDLT portal vein stenosis were excluded from this
      study. We analyzed the impact for persistent splenomegaly and hypersplenism after
      LDLT of pre-LDLT spleen volume, main portal vein (PV) size, coronary vein (CV)
      size and platelet levels. RESULTS: While 38 patients displayed splenomegaly, 121
      showed normal spleen volumes at 6 months after LDLT (LDLT). There were 119
      thrombocytopenic versus 40 normal platelet patients at 6 months post-LDLT. The
      persistent splenomegaly patients showed significantly larger pre-LDLT spleen
      volume, larger PV and CV sizes as well as lower platelet levels before
      (*10,000/mL) and 1 month after LDLT (*10,000/mL). Multiple logistic regression
      analysis showed spleen volume and platelet count at 1 month posttransplant to be
      the only variables associated with persistent splenomegaly at 6 months post.
      Persistent thrombocytopenia at 6 months post-LDLT was associated with
      significantly larger pre-LDLT spleen volume, larger CV size, and lower platelet
      levels including P0 and P1 m. Multiple logistic regression analysis showed that
      platelet count at 1 week and at 1 month post-LDLT were the variables associated
      with persistent thrombocytopenia at 6 months post-LDLT. CONCLUSION: Spleen volume
      and platelet levels at 1 month after LDLT may predict persistent splenomegaly at
      6 months post-LDLT. The predictive factors for hypersplenism at 6 months post
      LDLT may be platelet levels at 1 week and at 1 month post-LDLT.

PMID- 22483487
TI  - Partial splenic artery embolization for thrombocytopenia and uncontrolled massive
      ascites after liver transplantation.
AB  - Thrombocytopenia (platelet < 60,000/mm(3)) and uncontrolled massive ascites
      (ascitic fluid > 1000 mL/d over 10 days) after liver transplantation (OLT),
      although uncommon, usually represent serious complications. Splenectomy is a
      useful treatment despite its many side effects. Recently, partial splenic artery
      embolization (PSAE) is considered to be a nonsurgical, less invasive treatment.
      In this study, we retrospectively reviewed the results of PSAE after OLT. Between
      October 2008 and February 2010, 11 patients underwent PSAE after OLT due to
      thrombocytopenia (n = 6) or refractory ascites (RA; n = 5). Six patients (54.5%)
      were males and 3 (27.3%) were children. The primary liver disease was virus
      related liver cirrhosis (n = 6), biliary atresia (n = 3), fulminant hepatitis (n
      = 1), or alcoholic liver cirrhosis (n = 1). Seven grafts were from living and
      four from deceased donors. The major axial size of spleen was 12.1 to 23.4 cm and
      its average embolized volume, 76.4% (range = 70%-80%). As the result, the
      platelet count significantly increased after PSAE in all patients maintaining
      values greater than 100,000/mm(3) in four thrombocytopenic patients (66.7%).
      Cases of RA showed marked decreases after PSAE (100%). The follow-up was 6 to 28
      months. After PSAE, patients experienced abdominal pain (n = 9, 81.8%), fever (n
      = 2, 18.2%), and abdominal distension (n = 2, 18.2%). However, there was no
      serious complication after PSAE such as splenic abscess, rupture, pancreatic
      infarction, sepsis, or death. In conclusion, PSAE was effective and safe and can
      be the choice for thrombocytopenia or RA related to hypersplenism after OLT.

PMID- 22483488
TI  - Effect of pulmonary support using extracorporeal membrane oxygenation for adult
      liver transplant recipients with respiratory failure.
AB  - BACKGROUND: Adult liver transplantation (OLT) recipients occasionally show
      serious acute cardiopulmonary dysfunction, requiring intensive care. We assessed
      the role of extracorporeal membrane oxygenation (ECMO) support in adult
      recipients facing acute pulmonary failure and refractory to conventional
      mechanical ventilation and concurrent nitric oxide gas inhalation. METHODS: From
      January 2008 to March 2011, 18 adult OLT recipients at our institution required
      ECMO support: 12 due to pneumonia and 6 to adult respiratory distress syndrome.
      Their mean age was 55.7 +/- 6.9 years and mean Model for End-stage Liver Disease
      score, 24.8 +/- 8.5. Twelve patients had undergone living donor and six deceased
      donor OLT. RESULTS: A venovenous access mode and concurrent continuous venovenous
      hemodiafiltration were used in all patients. There were no procedure-related
      complications. Eight patients (44.4%) were successfully weaned from ECMO upon the
      first attempt after a mean support of 11.9 +/- 6.1 days, but the other 10 died
      due to overwhelming infection. Univariate analysis revealed no significant pre
      ECMO risk factor for treatment failure but C-reactive protein concentration at
      the time of ECMO differed significantly among patients who did versus did not
      survive after ECMO. CONCLUSIONS: ECMO as rescue therapy may be a final
      therapeutic option for OLT recipients with refractory pulmonary dysfunction who
      would otherwise die due to hypoxemia from severe pneumonia or adult respiratory
      distress syndrome.

PMID- 22483489
TI  - Risk factors and clinical outcomes of ventilator-associated pneumonia in patients
      on the liver transplant waiting list.
AB  - BACKGROUND: Prolonged intubation results in ventilator-associated pneumonia
      (VAP), which contributes to significant mortality among patients on the waiting
      list. The aim of this study was to determine the risk factors for and clinical
      outcomes of VAP among patients into the intensive care unit (ICU). METHODS: We
      enrolled 50 consecutive critically ill patients with end-stage liver disease
      admitted to the ICU from January 2005 through December 2010. All patients were
      intubated for more than 4 days; no definite infection was found initially. We
      evaluated potential risks factors for VAP and clinical outcomes. RESULTS:
      Smoking, underlying liver disease, and lobar focal consolidations were
      significant factors for patients with versus without VAP. Fourteen-day mortality
      rates were 61.5% for VAP versus 40.5% for patients without VAP. Twenty-eight-day
      mortality rates for both groups were 92.3% and 86.5%, respectively. Multivariate
      analysis failed to identify independent predictors of early 14-day mortality.
      CONCLUSIONS: Underlying liver disease and lobar focal consolidations were risks
      factors for VAP in patients with prolonged intubation. Patients with prolonged
      intubation have a dismal prognosis even without VAP. The clinical outcomes of
      patients with versus without VAP were similar. However, early liver
      transplantation (<14 days of intubation) improves the chance to rescue patients
      before development of VAP.

PMID- 22483490
TI  - Incidence and management of postoperative abdominal bleeding after liver
      transplantation.
AB  - PURPOSE: To assess the incidence and management of postoperative abdominal
      bleeding after orthotopic liver transplantation (OLT) and to identify risk
      factors for abdominal bleeding. METHODS: We retrospectively reviewed the medical
      records of 1039 patients who underwent OLT at our institution from January 2008
      to December 2010 seeking to identify subjects with posttransplantation abdominal
      bleeding, defined as any hemorrhage requiring radiologic intervention or
      laparotomy within the first month. RESULTS: Among the 1039 patients, 94 (9%)
      showed abdominal bleeding, occurring at a mean of 6.1 days (range, day 1 to 21
      days). Active bleeding was controlled by endovascular interventional techniques
      (n = 37; 39%), by surgical ligation or vascular reconstruction (n = 43; 46%), or
      by sequential combinations of endovascular intervention and surgery (n = 14;
      15%). The most frequent bleeding sites for radiologic intervention were the right
      inferior phrenic artery (n = 14), right and left epigastric arteries (n = 7),
      intercostal artery (n = 5) and right renal capsular artery (n = 4). The most
      frequent bleeding sites requiring laparotomy were the hepatic artery (n = 9),
      diaphragm (n = 8), inferior vena cava (n = 5), abdominal drain insertion site (n
      = 4), portal vein anastomosis site (n = 4), abdominal wall (n = 3), liver graft
      cut surface (n = 3), hilar plate (n = 3), and greater omentum (n = 3). Bleeding
      episodes were associated with greater patient age and increased intraoperative
      blood loss. CONCLUSIONS: The risk of bleeding from coagulopathy and iatrogenic
      injury is high during the early posttransplantation period. This risk of bleeding
      can be minimized by meticulous surgical dissection and bleeding control.

PMID- 22483491
TI  - Hepatic venous outflow obstruction in living donor liver transplantation: balloon
      angioplasty or stent placement?
AB  - BACKGROUND: The incidence of hepatic venous outflow obstruction (HVOO) has been
      reported to be 5%-13% when a partial graft is used for orthotopic liver
      transplantation (OLT). HVOO leads to graft congestion, portal hypertension, and
      finally cirrhosis, which jeopardizes both graft and recipient survivals. In this
      study, we sought to identify perioperative factors influencing HVOO and to
      investigate conditions that require stent placement. PATIENTS AND METHODS: From
      February 1994 to December 2010, we performed 40 living donor liver
      transplantations (LDLT). HVOO occurred in 5 cases (12.5%), all of which were left
      lobe grafts. Because HVOO was not observed in patients with body weight (BW) <30
      kg, we investigated the other 28 cases with BW >30 kg. RESULTS: There was no
      difference from unaffected subjects except for cold ischemic time (CIT), which
      was significantly longer: 86.2 +/- 10.4 minutes vs 46.0 +/- 4.8 minutes (P =
      .001). Balloon angioplasty, which was selected as the initial treatment for all
      stricture patients, improved 2 patients after 1 and 5 treatments, respectively,
      but 3 subjects underwent repeated HVOO, finally being treated with self
      expandable metallic stents at 9, 6, and 10 years after LDLT, respectively. All
      patients finally resolved their strictures. CONCLUSION: HVOO reflects intimal
      hyperplasia and fibrosis at the anastomotic sites or compression and twisting of
      the anastomosis caused by graft regeneration. In addition, progression of chronic
      rejection and fibrosis are possibly responsible for late-onset HVOO. Longer CIT
      possibly reflects difficulties in the venoplasty before anastomosis. No bleeding
      or thrombosis complications were observed during dilatation among our cases. The
      selection of the stent size for each case and careful stent deployment are
      important to prevent complications. Stent placement should be considered in
      patients with chronic rejection who are refractory to several balloon
      angioplasties with early-onset or late-onset HVOO.

PMID- 22483492
TI  - The 4-week serum creatinine level predicts long-term renal dysfunction after
      adult living donor liver transplantation.
AB  - OBJECTIVES: Recipients after liver transplantation. (OLT) often experience renal
      dysfunction. Acute kidney injury (AKI) and chronic kidney disease (CKD) after OLT
      occur among 20% to 50% and 30% to 90% of recipients, respectively; 2% to 5% of
      them deteriorate into end-stage renal disease each year. Since the predictable
      factors for CKD have not been well identified. We sought to investigate the
      incidence and predictors of CKD at 5 years after OLT. PATIENTS AND METHODS:
      Between August 2002 and December 2005, we enrolled 77 patients who underwent
      adult living donor OLT with over 2 years of follow-up. The strategies to prevent
      renal dysfunction included induction with basiliximab to delay the use of
      tacrolimus: addition of mycophenolate mofetil to reduce the tacrolimus dosage;
      avoidance of the calcineurin inhibitor using sirolimus or administration of an
      angiotensin II receptor antagonist. The clinical variables were reviewed for
      analysis. RESULTS: The mean follow-up was 76 +/- 14 months. The incidence of AKI
      (over 50% increase level of creatinine) was 29%. Ten (13.0%) patients developed
      CKD (creatinine > 2 mg/dL). One (1.3%) subject developed end-stage renal disease
      requiring hemodialysis. Upon multivariate analysis the development of CKD was
      significantly associated with the posttransplant 4-week creatinine level: 0.92 +/
      0.23 versus 1.37 +/- 0.93 mg/dL (P = .008). CONCLUSION: The 4-week creatinine
      value was predictive of the occurence of CKD over 5 years after OLT.

PMID- 22483493
TI  - The ratio of plasma neutrophil gelatinase-associated lipocalin predicts acute
      kidney injury in patients undergoing liver transplantation.
AB  - BACKGROUND: Postoperative acute kidney injury (AKI) is associated with high
      morbidity and mortality after liver transplantation (OLT). Previous studies have
      shown the value of plasma neutrophil gelatinase-associated lipocalin (NGAL) taken
      2 hours after reperfusion of the liver graft as an early marker predicting AKI.
      The study was performed to determine whether plasma NGAL concentrations obtained
      as early as 1 hour after reperfusion was predictive of AKI and whether the NGAL
      ratio was an early predictor for AKI in the first 48 hours after OLT. METHODS:
      Twenty-six liver transplant recipients donated plasma samples for NGAL
      determinations at induction (T1), at graft reperfusion (T3) as well as after 1
      (T4) and hours 2 (T5), and at the end of the surgery (T7). AKI was defined at 48
      hours after liver transplantation according to the acute kidney injury network
      criteria. Predictive ability was assessed using areas under the curve of receiver
      operator characteristic analyses. RESULTS: The area under the curve of the
      receiver operator characteristics curve of (plasma NGAL concentration at
      T4)/(plasma NGAL concentration at T1) to predict AKI was 0.717 at T5, 0.765 at
      T7, 0.714 at T8 (24 hours post-OLT), and 0.781 at T9 (48 hours post-OLT).
      CONCLUSION: The plasma NGAL concentrations taken 1 hour after reperfusion of the
      liver graft seem to be predictive of AKI; the NGAL changing ratio may be an early
      predictor for AKI in the first 48 hours after OLT.

PMID- 22483494
TI  - Varicella zoster virus disease after pediatric living donor liver
      transplantation: is it serious?
AB  - OBJECTIVES: The aim of this study was to evaluate patients who developed
      varicella zoster virus (VZV) disease after pediatric living donor liver
      transplantation (PLDLT). METHODS: Two hundred fifty-five patients who underwent
      PLDLT between 1995 and 2010 were included in this study. Pretransplantation
      vaccination of VZV was performed for all recipients except emergency PLDLTs.
      Posttransplantation VZV vaccination was administered to the patients with a low
      VZV antibody titer 2 years or more after transplantation. The clinical course and
      outcomes of VZV disease in cases were reviewed with the transplant database and
      hospital medical records. RESULTS: Sixty-three patients developed VZV disease
      (chicken pox in 61, herpes zoster in 2) at a median onset of 36 months after
      PLDLT and at a median age of 4 years old, with a cumulative incidence of 25%. All
      chicken pox occurred in VZV antibody-negative patients. The onset of herpes
      zoster in the two patients occurred within 3 months after PLDLT; in addition,
      these patients were VZV antibody-positive patients. The clinical presentations of
      most patients were not serious and there were no disseminated infections.
      Although only 3 patients (5%) were hospitalized, the other 60 patients (95%) all
      showed a good response to oral antiviral therapy. CONCLUSIONS: Although VZV
      disease is an infectious disease with a high morbidity rate after PLDLT, it can
      normally be successfully managed on an outpatient basis at home. Pre- and
      posttransplantation vaccinations are effective for delaying the onset of chicken
      pox after PLDLT and to prevent it from developing into a serious illness.

PMID- 22483495
TI  - The risk factors for early infection in adult living donor liver transplantation
      recipients.
AB  - OBJECTIVE: The high rate of early major infections in liver transplantation
      recipients is due to their compromised immune-system. We examined the risk
      factors of early major infection in living donor liver transplantation (LDLT).
      MATERIALS AND METHODS: From January 2004 to December 2010, 242 patients
      undergoing LDLT were enrolled in the prospective cohort. We prospectively
      collected their clinical and demographic variables, operative details, and
      posttransplant complications. RESULT: One hundred thirty-nine patients (57.7%)
      experienced 252 episodes of early infection posttransplantation: bloodstream
      septicemia (n = 46, 18.3%), urinary tract (n = 34; 14.1%), pneumonia (n = 64;
      25.4%), peritonitis (n = 62; 25.7%), and catheter related (n = 46; 19%). The most
      frequent Gram-positive bacteria were coagulase-negative staphylococci (n = 52;
      16.9%), followed by Staphylococcus aureus (n = 32; 10.4%). The most common Gram
      negative bacteria were Escherichia coli (n = 27; 8.8%); Acinetobacter baumannii
      (n = 29; 9.4%), Pseudomonas aureos (n = 18; 5.8%), and Sternotrophomonas
      maltophilia (n = 18; 5.8%). Upon multivariate logistic regression analysis, the
      risk factors for early major infection were a high creatinine level (odds ratio =
      1.481), a long anhepatic arterial phase (1.01), a reoperation (6.417), young age
      (1.040), and non-hepatocellular carcinoma recipient (2.141). CONCLUSION: Early
      major infection after LDLT was high with Gram-positive bacteria, the most common
      etiologies. Prolonged anhepatic arterial phase, renal insufficiency, and
      reoperation were risk factors for an early major infection.

PMID- 22483496
TI  - Antiviral prophylaxis versus preemptive therapy to prevent cytomegalovirus
      infection and related death in liver transplantation: a retrospective study with
      propensity score matching.
AB  - BACKGROUND: Cytomegalovirus (CMV), the most significant viral infection in liver
      transplant recipients, is addressed by 2 methods: Preemptive therapy (PT) or
      universal prophylaxis (UP). METHODS: We analyzed medical records including at
      least 1 year follow-up of patients who underwent liver transplantation from 2006
      to 2009 in 3 tertiary hospitals. PT was used in 2 hospitals (PT group), whereas
      UP with valganciclovir for 3 months was adopted in the other hospital (UP group).
      The 2 groups were matched using propensity scoring by perioperative variables. We
      performed a 1:1 comparison of the efficacy of UP and PT. RESULTS: We analyzed 634
      liver transplant patients, including 562 matched subjects. Baseline
      characteristics and underlying liver status were comparable. CMV immunoglobulin G
      of recipients was positive in 98.9% of the PT group and 99.3% of the UP group.
      CMV viremia episodes that required administration of an antiviral agent occurred
      in 26 (9.3%) PT and 37 (13.2%) UP subjects (P = .18). CMV-related mortalities
      were similar (0.7% vs 1.8%; P = .45), but all-cause mortality was higher in the
      PT group (18.5% vs 13.2%; P = .08). CONCLUSION: The efficacy of PT was similar to
      UP to prevent CMV disease and related mortality among a group at moderate risk
      for CMV infection.

PMID- 22483497
TI  - Preemptive antiviral treatment for hepatitis C virus after living donor liver
      transplantation.
AB  - BACKGROUND: Recurrence following liver transplantation for hepatitis C virus
      (HCV), which is universal, affects long-term outcomes. Treatment with interferon
      (IFN) and ribavirin (RBV), the only widely available options at this time, have
      been faced with low tolerability and overall unsatisfactory results in deceased
      donor liver transplantation (DDLT). However, its place after living donor liver
      transplantation (LDLT) remains a matter of debate. Since most LDLT cases are
      performed in a planned manner at a lower Model for End-stage Liver Disease (MELD)
      score compared to DDLT, we have aggressively applied preemptive INF/RBV in our
      series. PATIENTS AND METHODS: We studied 122 adult recipients who underwent LDLT
      for HCV-related end-stage liver disease. The preemptive IFN/RBV protocol
      initiated treatment promptly after improvement in the patient's general condition
      with a low-dose IFN alpha2b and RBV (400 mg/d) followed by a gradual increase in
      the INFalpha2b dosage. Finally, we applied pegylated IFN (1.5 ug/kg/wk) and RBV
      (800 mg/d). The treatment was continued for 12 months after serum HCV-RNA became
      negative, which was defined as the end-of-treatment response (ETR). The response
      was considered to be a sustained viral response (SVR) if there were negative
      serologic results without antiviral treatment for another 6 months. Splenectomy
      was performed at the time of LDLT to improve tolerability to INF/RBV. The median
      age of the patients was 55 yrs (range = 23-66), with male dominance (87 males and
      35 females). Median MELD score was 14 (range = 6-48). The series included 72
      patients with hepatocellular carcinomas, and six with HIV coinfections. In 98
      cases, HCV genotype was 1b. RESULTS: Overall survival at 5 years was 79%.
      Cumulative response rates under the protocol were ETR 56% and SVR 44% at 5 years.
      CONCLUSIONS: Preemptive IFN/RBV therapy after LDLT for HCV is feasible with
      acceptable outcomes.

PMID- 22483498
TI  - Early bloodstream infection after pediatric living donor living transplantation.
AB  - To determine the perioperative risk factors for bacterial infections after
      pediatric living donor liver transplantation (LDLT), we investigated the clinical
      profiles of 149 children who underwent pediatric LDLT between 1994 and 2008.
      Bacterial infections were diagnosed based on guidelines proposed by the Centers
      for Disease Control. We observed 36 bloodstream infections (BSIs) in 32/149
      (21.5%) patients (0.24 infections per patient), which, 21 (58.3%) BSIs in 19
      patients were due to gram-positive and 15 (41.7%) in 13 patients to gram-negative
      organisms. The most common pathogens of early BSI were coagulase-negative
      Staphylococcus; (n = 11; 30.6%) and Klebsiella pneumoniae (n = 8; 22.2%). The
      most common site of early BSI was catheter-related (n = 14; 38.9%). Multivariate
      analysis showed that age <= 1 year (P < .05; odds ratio [OR] = 3.90; 95% CI, 1.83
      15.26) and bile duct complications (P < .05; OR = 6.2, 95% CI = 3.21-35.23) were
      significant independent risk factors for early BSIs. More cautious management of
      pediatric LDLTs may be necessary for younger age children particularly with
      postoperative biliary complications.

PMID- 22483499
TI  - The relationship between recurrences and immunosuppression on living donor liver
      transplantation for hepatocellular carcinoma.
AB  - OBJECTIVES: Living donor liver transplantation (LDLT) offers timely
      transplantation for patients with hepatocellular carcinoma (HCC). If ABO
      incompatible LDLT is feasible, the needs for pretransplantation treatments may be
      eliminated. It is known that negative impacts of immunosuppression are limited
      among LDLT for HCC, however, we believe that excessive immunosuppression is one
      of the risk factors for recurrence. We compared the impacts of immunosuppression
      for LDLT with hepatectomy outcomes for HCC. METHODS: From 1991 to 2010, we
      performed 144 LDLTs including 14 patients with HCC. Seven met the Milan criteria.
      Immunosuppressive therapies were based on tacrolimus plus methylprednisolone plus
      CD25 antibody. For ABO-incompatible cases, we also used mycophenolate mofetil and
      rituximab. Five cases underwent strong imunosuppressive therapy (steroid pulse or
      rituximab) within 180 days. In addition, we performed hepatectomy for 180 HCC
      cases from 1997 to 2010. RESULTS: Overall survival rates of the LDLT cohort and
      hepatectomy groups were similar, but disease-free 5-year survival rates (DFS) of
      the LDLT cohort were significantly better than those of the hepatectomy group
      (total = 54.4% versus 27.4%, within the Milan criteria cases, 71.4% versus
      33.8%). Thus, the negative impact of immunosuppression on recurrence was less
      than the benefit of a whole liver resection. Among strongly immunosuppressed
      cases, 5-years DFS rates were significantly worse than among other
      immunosuppressed cases (20.0% versus 76.2%). Upon univariate analysis, the
      factors associated with HCC recurrence were alpha-fetoprotein levels and steroid
      doses within 180 days, but multivariate analysis did not show a predictor for
      recurrence. CONCLUSION: Patients who are strongly immunosuppressed may have
      several negative impacts for recurrences. More careful indications must be
      selected for ABO-incompatible cases.

PMID- 22483500
TI  - De novo malignancies after liver transplantation: incidence comparison with the
      Korean cancer registry.
AB  - PURPOSE: De novo malignancy is not uncommon after liver transplantation (OLT). We
      have compared the incidence of novo malignancy following OLT with those among the
      general Korean population. METHODS: Between January 1998 and December 2008, 1952
      adult OLT were performed, including 1714 living donor and 238 deceased donor
      grafts whose medical records were retrospectively reviewed. RESULTS: Among the
      1952 patients, 44 (2.3%) showed de novo malignancies after a mean posttransplant
      period of 41 months. Among the 14 types of malignancy the most frequent was
      stomach cancer (n = 11; 25.0%), colorectal cancer (n = 9; 20.5%), breast cancer
      (n = 4; 9.1%), and thyroid cancer (n = 3; 6.8%). These patients underwent
      aggressive treatment, including surgery, chemotherapy, and radiotherapy, except
      for one patient with an aggressive primary liver cancer. Over a mean follow-up of
      45 months after diagnosis of de novo malignancy, 13 patients (29.5%) died; the
      overall 3-year patient survival rate was 67.5%. The relative risk of malignancy
      following OLT was 7.7-fold higher in men and 7.3-fold higher in women than the
      Korean general population. CONCLUSIONS: OLT recipients must be checked
      periodically for de novo malignancy throughout their lives, especially for
      cancers common in the general population.

PMID- 22483501
TI  - Magnetic compression anastomosis for bile duct stenosis after donor left
      hepatectomy: a case report.
AB  - Magnetic compression anastomosis (MCA) provides a minimally invasive treatment
      creating a nonsurgical, sutureless enteric anastomosis in conjunction with an
      interventional radiologic technique by using 2 high-power magnets. Recently, the
      MCA technique has been applied to bile duct strictures after living donor liver
      transplantation or major hepatectomy. Herein we described use of MCA for bile
      duct stenosis 5 months after donor left hepatectomy in a 24-year-old man who
      presented with a stricture at the porta hepatis and intrahepatic bile duct
      dilatation. Unsuccessful transpapillary biliary drainage and balloon dilatation
      through a percutaneous transhepatic biliary drainage (PTBD) route led to the MCA.
      A 4-mm-diameter cylindrical samarium-cobalt (Sm-Co) daughter magnet with a long
      nylon wire was placed at the superior site of the obstruction through the PTBD
      route. A 5-mm-diameter Sm-Co parent magnet with an attached nylon handle was
      endoscopically inserted into the common bile duct and placed at the inferior site
      of obstruction. The 2 magnets were attracted, sandwiching the stricture and
      establishing a reanastomosis. In conclusion, the MCA technique was a unique
      procedure for choledochocholedochostomy in a patient with bile duct stenosis
      after donor hepatectomy.

PMID- 22483502
TI  - Veno-occlusive disease/sinusoidal obstruction syndrome associated with potential
      antibody-mediated rejection after pediatric living donor liver transplantation: a
      case report.
AB  - A 9-month-old girl with biliary atresia underwent successful living donor liver
      transplantation from her 42-year-old ABO blood-type incompatible mother. The
      postoperative course was uneventful until postoperative day (POD) 13 when the
      recipient displayed an increased volume of drained ascites and decreased her
      platelet count showing low-velocity portal venous inflow without hepatic venous
      outflow obstruction. We suspected potential veno-occlusive disease/sinusoidal
      obstruction syndrome (vod/sos) due to an acute cellular rejection (ACR) episode
      and performed a liver biopsy (LB). We diagnosed severe episode (Rejection
      Activity Index Score; P3V3B1 = 7) and started steroid pulse therapy. We performed
      a second LB on POD 27 because the patient showed weight gain and tender
      hepatomegaly, diagnosing moderate ACR (P1V3B1 = 5). We started a second course of
      steroid pulse therapy, but the patient's clinical findings did not improve. On
      POD 43, her third LB finding showed P1V1B1 with improved processes from ACR, but
      still displaying severe congestion and fibrotic obliteration of small hepatic
      veins. We suspected that her immunologic responses were associated with antibody
      mediated rejection (AMR) because her anti-HLA class I and class II antibodies
      were positive by flow panel-reactive antibody method and donor-specific antigen
      class II and C4d staining were also positive. We added mycophenolate mofetil and
      administered high-dose intravenous immunoglobulin to control the AMR, and
      anticoagulant therapy for the VOD/SOS. Her clinical findings and graft venous
      abnormalities finally improved; she was eventually discharged without sequelae on
      POD 72.

PMID- 22483503
TI  - Hepatic venous congestion after living donor liver transplantation: quantitative
      assessment of liver stiffness using shear wave elastography--a case report.
AB  - We report a 49-year-old right lobe liver transplant recipient, who developed a
      significant anastomotic stenosis of the right hepatic vein shortly thereafter.
      Shear wave elastography (SWE) was applied to investigate liver stiffness
      quantitatively. It showed increased stiffness in the anterior compared with the
      posterior segment of right lobe graft. The stenotic right hepatic venous
      anastomosis was then managed by angioplasty with stent placement. SWE after
      angioplasty showed a gradual decrease in stiffness of the anterior segment, which
      was almost equal to the posterior segment at 2 weeks thereafter. Our experience
      suggested that SWE may be a noninvasive tool to assess alterations in liver
      stiffness secondary to hepatic venous congestion after liver transplantation.

PMID- 22483504
TI  - Successful treatment with continuous enteral protease inhibitor in a patient with
      severe septic shock.
AB  - OBJECTIVE: The mortality rate among patients with septic shock is high despite
      current therapy. We present a case of Fournier's gangrene and septic shock at 4
      years post-heart transplantation that was reversed by "continuous enteral
      feeding" of the digestive enzyme inhibitor, gabexate mesilate. Recently, powerful
      pancreatic digestive proteases in the lumen of the intestine have been identified
      as initiators of the systemic inflammatory response. Intraluminal inhibitions of
      the proteases significantly attenuates intestinal damage, system inflammation,
      and multiorgan failure in experimental forms of shock but it has not been tested
      in man. METHODS AND RESULTS: Gabexate mesilate, a synthetic digestive protease
      inhibitor, was continuously administered in two liters of crystalloid solution to
      a patient by enteral feeding during septic shock. The condition and markers for
      shock due to sepsis reversed in a few days. CONCLUSION: This case suggested that
      "enteral" digestive protease inhibition may decrease and even reverse the
      sequelae of shock and sepsis.

PMID- 22483505
TI  - Successful laparoscopic-assisted hemostasis of intrathoracic massive vericeal
      rupture during living related liver transplantation: a case report.
AB  - End-stage liver disease that requires transplantation is usually accompained by
      esophagogastric or another collateral vessel varices. Sometimes, the
      esophagogastric varices rupture intraoperatively during liver transplantation.
      However we have reported rare case of rupture of an intercostal varicose vein,
      which was controlled successfully by flexible laparoscopy. The patient was a 62
      year-old man, who suffered decompensated liver cirrhosis with hepatocellular
      carcinoma. The Child-Pugh score was 11 and the Model for End-stage Liver Diseases
      score was 14. Preoperative gastrointestinal fiberscopy and colon fiberscopy
      examinations revealed esophagogastric and rectal varices. He underwent living
      related liver transplantation from his son on February 10, 2010. Just after the
      liver transplantation, the patient's blood pressure tended to decrease. Chest
      radiography demonstrated a massive right pleural effusion. We drained 3000 mL of
      blood by thoracic puncture. Therefore we reoperated him for the question an
      intrathoracic variceal hemorrhage. We confirmed variceal bleeding after removal
      of the massive hematoma by opening the diaphragm. However, we could neigher show
      directly the bleeding point in the anterior thorax nor stop it because of the
      constriction of the diaphragm. Therefore we used a flexible laparoscope to both
      confirm the bleeding point and to achieve hemostasis. We believe that
      theoperative compression of the intercostal varicose vein by a retractor induced
      the vascular rupture.

PMID- 22483506
TI  - Genome architecture and expression.

PMID- 22483507
TI  - The pathogenesis of measles.
AB  - Measles is an important cause of childhood morbidity and mortality in developing
      countries. Measles virus (MV) is transmitted via the respiratory route and causes
      systemic disease. Over the last decade, identification of new cellular receptors
      and studies in animal models have challenged the historic concepts of measles
      pathogenesis. It is thought that MV enters the host by infection of alveolar
      macrophages and/or dendritic cells in the airways, and is amplified in local
      lymphoid tissues. Viremia mediated by infected CD150+ lymphocytes results in
      systemic dissemination. Infection of lymphocytes and dendritic cells in the
      respiratory submucosa facilitates basolateral infection of epithelial cells via
      the newly identified receptor Nectin-4. Concomitant and extensive epithelial
      damage may contribute to efficient transmission to the next host.

PMID- 22483508
TI  - The use of executed Nazi victims in anatomy: Findings from the Institute of
      Anatomy at Giebetaen University, pre- and post-1945.
AB  - There is increasing evidence that both during the time of National Socialism, and
      in the post-World War II-period, the corpses of executed victims of the Nazi
      regime, as well as body parts taken from them were used for teaching and research
      purposes in German anatomical institutes. The paper addresses the related issues
      by looking at the case of the Institute of Anatomy at Giebetaen University whose
      director, Ferdinand Wagenseil, is documented to have had certain political
      reservations towards the Nazi regime, but at the same time used the situation to
      get access to more corpses, most likely for teaching purposes. On a second level,
      new archival sources are used to explore to what extend corpses and body parts of
      Nazi victims were used in the post-WW II period. One central aim in this context
      is the reconstruction of the identities of these victims for the purpose of
      acknowledgment of the atrocities committed to them, appropriate remembrance, and
      to possibly enable the respectful burial of the remaining body parts. Further,
      the case raises the question how anatomists during and after the Nazi period
      justified for themselves the use of corpses from executed political prisoners,
      and what might be potential explanations for their reasoning. The historical
      evidence documents an attitude and value hierarchy which is aware of the
      disregard of dignity or human rights in the case of the Nazi victims, but which
      perceives this disregard as of minor relevance compared to the needs of medical
      teaching, or medical research. It is argued that this mental attitude is not
      specific for the Nazi period, but that it has been brought to an extreme
      manifestation in this specific context.

PMID- 22483509
TI  - Responses of conventional and molecular biomarkers in turbot Scophthalmus maximus
      exposed to heavy fuel oil no. 6 and styrene.
AB  - Several accidental spills in European coastal areas have resulted in the release
      of different toxic compounds into the marine environment, such as heavy fuel oil
      type no. 6 in the "Erika" and "Prestige" oil spills and the highly toxic styrene
      after the loss of the "Ievoli Sun". There is a clear need to develop tools that
      might allow assessing the biological impact of these accidental spills on aquatic
      organisms. The aim of the present study was to determine the short-term effects
      and recovery after exposure of juvenile fish (Scophthalmus maximus) to heavy fuel
      oil no. 6 and styrene by using a battery of molecular, cell and tissue level
      biomarkers. Turbots were exposed to styrene for 7 days and to the diluted soluble
      fraction of the oil (10%) for 14 days, and then allowed to recover in clean
      seawater for the same time periods. cyp1a1 transcript was overexpressed in
      turbots after 3 and 14 days of exposure to heavy fuel oil, whereas ahr
      transcription was not modulated after heavy fuel oil and styrene exposure.
      pparalpha transcription level was significantly up-regulated after 3 days of
      treatment with styrene. Liver activity of peroxisomal acyl-CoA oxidase (AOX) was
      significantly induced after 14 days of oil exposure, but it was not affected by
      styrene. Hepatocyte lysosomal membrane stability (LMS) was significantly reduced
      after exposure to both treatments, indicating that the tested compounds
      significantly impaired fish health. Both AOX and LMS values returned to control
      levels after the recovery period. No differences in gamete development were
      observed between fuel- or styrene- exposed fish and control fish, and
      vitellogenin plasma levels were low, suggesting no xenoestrogenic effects of fuel
      oil or styrene. While styrene did not cause any increase in the prevalence of
      liver histopathological alterations, prevalence of extensive cell vacuolization
      increased after exposure to heavy fuel oil for 14 days. In conclusion, the suite
      of selected biomarkers proved to be useful to determine the early impact of and
      recovery from exposure to tested compounds in turbot.

PMID- 22483510
TI  - Body mass index and mortality in acute myocardial infarction patients.
AB  - BACKGROUND: Previous studies have described an "obesity paradox" with heart
      failure, whereby higher body mass index (BMI) is associated with lower mortality.
      However, little is known about the impact of obesity on survival after acute
      myocardial infarction. METHODS: Data from 2 registries of patients hospitalized
      in the US with acute myocardial infarction between 2003-2004 (PREMIER) and 2005
      2008 (TRIUMPH) were used to examine the association of BMI with mortality.
      Patients (n=6359) were categorized into BMI groups (kg/m(2)) using baseline
      measurements. Two sets of analyses were performed using Cox proportional hazards
      regression with fractional polynomials to model BMI as categorical and continuous
      variables. To assess the independent association of BMI with mortality, analyses
      were repeated, adjusting for 7 domains of patient and clinical characteristics.
      RESULTS: Median BMI was 28.6. BMI was inversely associated with crude 1-year
      mortality (normal, 9.2%; overweight, 6.1%; obese, 4.7%; morbidly obese; 4.6%; P
      <.001), which persisted after multivariable adjustment. When BMI was examined as
      a continuous variable, the hazards curve declined with increasing BMI and then
      increased above a BMI of 40. Compared with patients with a BMI of 18.5, patients
      with higher BMIs had a 20% to 68% lower mortality at 1 year. No interactions
      between age (P=.37), sex (P=.87), or diabetes mellitus (P=.55) were observed.
      CONCLUSIONS: There appears to be an "obesity paradox" among patients after acute
      myocardial infarction such that higher BMI is associated with lower mortality, an
      effect that was not modified by patient characteristics and was comparable across
      age, sex, and diabetes subgroups.

PMID- 22483511
TI  - Predictors of positive and negative attitudes toward their condition in Turkish
      individuals with epilepsy.
AB  - The purpose of this cross-sectional study was to explore the attitudes of
      individuals with epilepsy (IWE) toward their condition via self-reported changes
      in the feelings/thoughts about having epilepsy. We aimed to investigate whether
      individuals with epilepsy perceive a change in their initial attitudes toward the
      condition over time. Additionally, if a change was perceived, the variables which
      predict the current thoughts/feelings toward epilepsy were also examined. Seventy
      adult IWE participated in the study. Of the 70 participants in the study, 25.7%
      retained their initial feelings/thoughts without any change. Among the IWE who
      reported no-change, the most common category was "negative from the beginning".
      On the other hand, 74.3% of the participants reported a change. Of the 74.3% of
      participants reporting change, the most common direction was from negative to
      positive" (79.2%) seeming to indicate a positive adjustment over the passage of
      time. In a logistic regression, only three factors were found to predict positive
      feelings/thoughts toward epilepsy: a clear understanding of the condition, low
      levels of depression and current employment status. Finally, there is a
      discussion of the potential applications of the IWE' self-assessment of their
      attitudes.

PMID- 22483512
TI  - Zinc and skin: a brief summary.
AB  - Zinc is an essential trace element that is an integral component of many metallo
      enzymes in the body and thus serves many biological functions. The clinical
      presentation of zinc deficiency varies and depends on serum zinc level. Whereas a
      significantly low serum zinc level results in clinical features similar to
      acrodermatitis enteropathica, mild hypozincemia presents with a less
      characteristic appearance; hence it may be underdiagnosed. Recognition of various
      cutaneous lesions is required for suspecting and identifying cases of zinc
      deficiency. Although many laboratory tests are useful, therapeutic response in
      suspected cases remains the gold standard of diagnosis. Serum zinc estimation
      alone is not very reliable because disease activity may not necessarily correlate
      with serum zinc level. Zinc supplementation results in a rapid response and the
      skin lesions heal without permanent sequelae. However, pigmentary alterations may
      persist longer. Predisposing factors should be identified and corrected. This
      brief review summarizes the identification and management of clinical zinc
      deficiency.

PMID- 22483513
TI  - Effective treatment of etanercept and phototherapy-resistant psoriasis using the
      excimer laser.
AB  - Treatment of moderate-to-severe plaque psoriasis often requires the use of
      phototherapy or systemic therapy, which includes immunosuppressants, retinoids,
      and biologic agents. Although biologic use is becoming increasingly popular, it
      is not uncommon for patients to experience treatment failure. We describe a
      patient who had a suboptimal response to etanercept monotherapy after twelve
      weeks of induction dosing (50 mg twice weekly), as well as to a combination of
      etanercept (50 mg once weekly-maintenance dosing) and narrowband ultraviolet B
      (NB-UVB) phototherapy three times weekly for an additional twelve weeks.
      Noticeable improvement was noted after the addition of NB-UVB and the patient's
      promising response to phototherapy influenced further management. Etanercept and
      NB-UVB were discontinued and the patient was initiated on excimer laser
      treatments twice weekly. After 4 weeks, the patient had a 75 percent reduction in
      Psoriasis Area Severity Index (PASI) score and after 7 weeks had over 95 percent
      clearance of psoriasis. The unique properties of the excimer laser may account
      for its clinical efficacy in our patient as well as in other cases of
      recalcitrant psoriasis. We propose that the excimer laser be considered in cases
      of biologic or conventional phototherapy failure in addition to being a standard
      treatment option or adjunct for the treatment of psoriasis.

PMID- 22483514
TI  - Primary ecthyma gangrenosum as a presenting sign of leukemia in a child.
AB  - Ecthyma gangrenosum is a type of skin infection characterized by black eschars on
      an erythematous base. It most commonly occurs with pseudomonas infection in an
      immunocompromised setting. We present a case of primary ecthyma gangrenosum as
      the presenting sign of pre-B acute lymphoblastic leukemia (ALL) in a child.

PMID- 22483515
TI  - Pyogenic granuloma-like Kaposi sarcoma: a diagnostic pitfall.
AB  - Pyogenic granuloma-like Kaposi sarcoma (PG-like KS) is a clinicopathologic
      variant of Kaposi sarcoma (KS), a vascular tumor caused by human herpesvirus-8
      (HHV-8). PG-like KS is a challenging entity to diagnose because its clinical and
      histological features encompass both pyogenic granuloma (PG) and KS
      characteristics. Immunhistochemical staining with HHV-8 latent nuclear antigen-1
      (LNA-1) has been shown to exhibit high sensitivity and specificity for diagnosing
      KS. Therefore, the integration of clinical features and context, histopathogical
      findings, and immunohistochemical analysis is important in obtaining the correct
      diagnosis of PG-like KS. We report a case of PG-like KS in an HIV-positive man.

PMID- 22483516
TI  - [Mycosis fungoides in children and adolescents: a report of six cases with
      predominantly hypopigmentation, along with a literature review].
AB  - Mycosis fungoides (MF), the most common form of cutaneous T cell lymphoma (CTCL),
      is mainly manifested in the elderly. However, it has been described in children
      and teenagers. OBJECTIVES: To report six patients with mycosis fungoides
      diagnosed in patients under 20 years of age. Our focus is on epidemiologic data,
      clinical features, histopathological aspects, and immunophenotypical findings.
      METHODS: The files of all patients diagnosed with CTCL at Hospital Universitario
      Antonio Pedro (HUAP) / Universidade Federal Fluminense (UFF), Niteroi, Brazil,
      from 2007 to 2010 were searched to identify patients under 20 years of age.
      Slides were reviewed with routine methods (H&E) and immunohistochemical stains by
      two dermatopathologists and one surgical pathologist. RESULTS: Among a total of
      66 patients with MF, six were children and adolescents between five and nineteen
      years of age. Most of them had dark skin and presented with the hypopigmented
      variant of MF; some expressed the T cell CD8+ phenotype, although the prognosis
      remains the same as for classical CTCL. The main histopathological findings were
      basilar lymphocytes, Pautrier microabscesses, eccrine infiltration, and dermal
      fibrosis. One patient had shown pityriasis lichenoides chronica for 10 years
      before the diagnosis of MF. CONCLUSIONS: The incidence of juvenile mycosis
      fungoides has increased, corresponding to 9.1 percent of patients diagnosed with
      MF in our institution in four years. In this sample, 83.3 percent of the patients
      had the hypopigmented variant and 50 percent of them showed the CD3+/CD8+ T cells
      phenotype. We emphasize the occurrence of pityriasis lichenoides chronica before
      the onset of MF in one of our cases. This association, although rare, must be
      considered in cases of atypical evolution of PLC. The diagnosis of hypopigmented
      MF should also be considered in patients when hypochromic patches are persistent.
      We would like to highlight the importance of Pautrier microabscesses, basilar
      distribution, and eccrine involvement by neoplastic lymphocytes as
      histopathological diagnostic criteria for this variant of MF.

PMID- 22483517
TI  - The Rudolph sign of nasal vestibular furunculosis: questions raised by this
      common but under-recognized nasal mucocutaneous disorder.
AB  - Nasal vestibular furunculosis is a mucocutaneous disorder commonly seen in the
      general population. Despite its prevalence in clinical practice, it has been
      inconsistently described and labeled in the medical literature. We present a case
      of nasal vestibular furunculosis presenting as recurrent exquisitely tender
      unilateral erythema and edema of the nasal tip (i.e., the Rudolph sign--as in
      Rudolph The Red Nosed Reindeer). This symptom complex responded rapidly to
      topical intranasal mupirocin ointment treatment after having previously failed
      other treatments including a topical intranasal triple antibiotic ointment and
      oral doxycycline. This case is instructive as it describes a heretofore under
      recognized, but not uncommon, mucocutaneous clinical entity that has been linked
      to more serious head and neck infections and likely has relevance to the
      intranasal carriage of Staphylococcus aureus. We review the limited published
      literature on this mucocutaneous disorder including its nosology and propose
      future lines of investigation for better defining its clinical significance and
      pathogenesis.

PMID- 22483518
TI  - Granuloma annulare arising in association with pulmonary coccidioidomycosis.
AB  - Granuloma annulare (GA) is a reactive process in the dermis, related to
      degeneration of collagen. It may occur as an idiopathic phenomenon or in
      conjunction with a myriad of systemic conditions, including infectious disease.
      We report an interesting case of GA precipitated by pulmonary coccidioidomycosis.

PMID- 22483519
TI  - Eosinophilic annular erythema.
AB  - Eosinophilic annular erythema is a rare benign recurrent disease, originally
      described in children, characterized by the recurrent appearance of persistent
      non-pruritic, urticarial annular lesions. Histologically a perivascular
      infiltrate composed of lymphocytes and abundant eosinophils in the dermis is
      exhibited. We report the case of a 15-year-old boy who presented with a 4-year
      history of recurrent flares of erythematous annular plaques on the trunk and
      extremities. The lesions resolved spontaneously after 3-5 weeks with no
      accompanying signs. A biopsy showed a mainly perivascular lymphocytic infiltrate
      with numerous eosinophils in the dermis.

PMID- 22483520
TI  - Cutaneous mixed tumor with extensive chondroid metaplasia: a potential mimic of
      cutaneous chondroma.
AB  - True cutaneous chondromas are extremely rare. Previously they have reportedly
      been confused with soft tissue chondromas and cartilaginous developmental
      anomalies. Monophasic mixed tumor could potentially also be mistakenly diagnosed
      as a true cutaneous chondroma. We report a cutaneous mixed tumor with massive
      chondroid metaplasia that mimicked a true cutaneous chondroma. We also propose
      that cutaneous mixed tumor with chondroid metaplasia may better explain the
      presence of primary cartilaginous tumors in the skin and true cutaneous chondroma
      may not be a real entity.

PMID- 22483521
TI  - Coma blisters with hypoxemic respiratory failure.
AB  - A 24-year-old woman with quadriplegia was admitted with respiratory failure
      because of pneumonia. She was on multiple medications including diazepam,
      oxycodone, and amitriptyline, known to be associated with coma blisters, though
      she did not overdose on any of them. On hospital day 2, she developed multiple
      blisters on both sides of her right forearm and hand. Skin biopsy showed eccrine
      gland degeneration consistent with coma blisters. It was felt that hypoxemia from
      her pneumonia contributed to the development of these blisters, which occurred on
      both pressure and non-pressure bearing areas of the arm. Coma blisters are self
      limited skin lesions that occur at sites of maximal pressure, mostly in the
      setting of drug overdose. However, coma blisters may occur with metabolic and
      neurological conditions resulting in coma.

PMID- 22483522
TI  - Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma with a chronic
      and indolent course. Is this different from peripheral T cell lymphoma?
AB  - Cutaneous T cell lymphomas most commonly have a CD4+ memory T cell phenotype and
      exhibit a relatively indolent course, but may in rare cases present with a CD8+
      cytotoxic phenotype with a strikingly more aggressive clinical behavior. Primary
      cutaneous aggressive epidermotropic CD8+ T cell lymphoma is an extremely rare
      entity with distinct clinicopatological features. The clinical features and
      prognosis of the recently-described CD8+ peripheral lymphoma are very different
      from cytotoxic CD8+ epidermotropic lymphoma, but the histological and phenotypic
      characteristics are very similar. We report a new case of CD8+ epidermotropic
      lymphoma with a chronic course and suggest the possibility of an overlap between
      these two types of lymphoma.

PMID- 22483523
TI  - Cutaneous granulomatous vasculitis associated with chronic lymphocytic leukemia:
      case report and review of literature of a rare entity.
AB  - Cutaneous granulomatous vasculitis associated with lymphoproliferative disorders
      is a rare entity, with only 14 cases previously reported in the English
      literature. Patients generally present with nodules or ulcers involving the
      extremities, which can appear months or years before or after onset of systemic
      disease. Granulomatous vasculitis has a poor prognosis when associated with
      underlying lymphoproliferative disorders, with the majority of reported cases
      fatal. Knowledge of this unusual entity is important to allow for proper clinical
      evaluation, follow-up, and therapy. We report a 77-year-old female with chronic
      lymphocytic leukemia and granulomatous vasculitis, which highlights the features
      of this association, and expands the clinical data.

PMID- 22483524
TI  - Facial and axillary apocrine chromhidrosis.
AB  - Apocrine chromhidrosis is a rare, chronic, idiopathic disorder, characterized by
      the excretion of pigmented sweat. A 26-year-old woman presented with a 3-year
      history of dark blue secretions on bilateral malar cheeks. On examination, upon
      pressure on the cheeks, a dark blue fluid was expressed, which appeared to arise
      primarily from the follicle. The patient had not appreciated it, but on
      examination of her axillae, a very subtle blue coloring was observed.
      Histopathologic examination revealed apocrine glands in the deep reticular
      dermis. Bluish cytoplasmic granules were observed in the apocrine epithelium
      lining, which correspond to lipofuscin granules. The diagnosis of apocrine
      cromhidrosis was made. We began treatment with 20 percent aluminum chloride
      hexahydrate solution and capsaicin cream with poor tolerance. Finally, we treated
      with botulinum toxin type A with a successful response. We report a case of
      facial and axillary apocrine cromhidrosis with good response to botulinum toxin
      type A.

PMID- 22483525
TI  - Indurated vascular plaques on the legs of an 85-year-old woman.
AB  - This is a case of classic type Kaposi sarcoma occurring in an 85-year-old woman
      who presented with indurated vascular plaques on both legs below the knee that
      has been present for two years. A brief review of the literature on Kaposi
      sarcoma is included.

PMID- 22483526
TI  - Crowdsourcing for research data collection in rosacea.
AB  - Several medical crowdsourcing sites are available to patients online, but few
      studies in the literature have compared crowdsourced data to clinical trials.
      Herein, we compare data from rosacea patients from a major medical crowdsourcing
      site with those from randomized controlled trials.

PMID- 22483527
TI  - Polypoid dermatofibroma with a slim pedicle: a case report.
AB  - Dermatofibroma, also called cutaneous fibrous histiocytoma or sclerosing
      hemangioma, is a fairly common, benign cutaneous tumor. Polypoid dermatofibroma
      is an unusual and poorly recognized form of this entity. We describe a peculiar
      case of this variant presenting with a unique morphology characterized by a round
      flat shape with a slim pedicle, although its histopathological picture was rather
      typical of that of ordinary dermatofibroma.

PMID- 22483528
TI  - Adoption of a clinical decision support system to promote judicious use of
      antibiotics for acute respiratory infections in primary care.
AB  - PURPOSE: Overuse of antibiotics for acute respiratory infections (ARIs) in
      primary care is an established risk factor for worsening antimicrobial
      resistance. The "Reducing Inappropriate Prescribing of Antibiotics by Primary
      Care Clinicians" study is assessing the impact of a clinical decision support
      system (CDSS) on antibiotic prescribing for ARIs using a multimethod intervention
      to facilitate CDSS adoption. The purpose of this report is to describe use of the
      CDSS, as well as facilitators and barriers to its adoption, during the first year
      of the 15-month intervention. METHODS: Between January 1, 2010 and December 31,
      2010, 39 providers in 9 practices in US states participated in this study.
      Quarterly EHR based audit and feedback, practice site visits for academic
      detailing, performance review and CDSS training, and "best-practice"
      dissemination during two meetings of study participants were used to facilitate
      CDSS adoption. Mixed methods were used to evaluate adoption of the CDSS. Using
      data extracted from the EHR, CDSS use for ARI was calculated. To determine
      facilitators and barriers of CDSS adoption, semi-structured group interviews were
      conducted with providers and staff at each practice. RESULTS: During the first
      year of implementation, the ABX-TRIP CDSS was used 14,086 times for ARI
      encounters. Overall, practice use of the CDSS during ARI encounters ranged from
      39.4% to 77.2%. Median use of the CDSS for adult patients was 58.2% and 68.6% for
      pediatric patients. Key factors associated with CDSS adoption include the
      perception by providers that it assists with decision making and stimulates
      patient discussions, engagement of non-physician staff and an iterative CDSS
      development process. CONCLUSIONS: Adoption of a custom designed CDSS in the first
      year of implementation is promising. Successful implementation of such technology
      requires a focus not only on the technological solution itself, but on its
      integration with the entire clinical workplace.

PMID- 22483529
TI  - A severe form of epidermal nevus syndrome associated with brainstem and
      cerebellar malformations and neonatal medulloblastoma.
AB  - Here we report a boy with epidermal nevus syndrome associated with brainstem and
      cerebellar malformations and neonatal medulloblastoma. The patient had epidermal
      nevi and complicated brain malformations including macrocephaly with
      polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar
      hemispheres with small and maloriented folia. The patient died after surgical
      resection of medulloblastoma which was newly recognized on MRI at 51 days of age.
      Postmortem pathological examinations showed very unique and bizarre malformation
      of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse,
      irregular and bumpy surface, blurred border between the Purkinje cell layer and
      internal granule cell layer, and many foci of heterotopia in the cerebellar white
      matter. The brainstem showed multiple anomalies, including enlargement of
      superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior
      olivary nuclei. The unusual constellation of brain malformations of our patient
      will widen the spectrum of epidermal nevus syndrome.

PMID- 22483530
TI  - Non-traditional wearing positions of pedometers: validity and reliability of the
      Omron HJ-203-ED pedometer under controlled and free-living conditions.
AB  - OBJECTIVES: To test the validity and intra-instrument reliability of the HJ-203
      Omron pedometer when worn in different positions, under controlled and free
      living conditions. DESIGN: Cross-sectional. METHODS: Forty healthy adults (20
      men, 29.5+/-7.7 years) participated in three controlled tests, i.e. 20 step test,
      stair climbing (up and down), and treadmill walking (five bouts at different
      speeds). All participants wore a HJ-203 pedometer in the pants pocket, in a
      carrier bag, and around the neck. Fifty-four adults (23 men, 33.9+/-11.1 years)
      participated in a free-living conditions test, wearing a HJ-203 in the pants
      pocket and around the neck during one day. RESULTS: During controlled tests,
      absolute percentage error ranged between 0.1% and 14.0%. Accuracy was influenced
      by wearing position (p<0.001), walking speed (p<0.001), and wearing
      position*walking speed (p=0.001). Accuracy was poor for pedometers worn in the
      pants pocket, especially at slower speeds; and best when worn around the neck.
      During free-living conditions, APE ranged between 30.7% and 36.9% and did not
      differ statistically between pants pocket and neck position. Intra-instrument
      reliability varied for controlled tests (ICC=0.14-0.96) and was acceptable during
      free-living conditions (ICC=0.94). CONCLUSIONS: The HJ-203 Omron pedometer showed
      acceptable accuracy for all wearing positions during stairs walking and treadmill
      walking at higher speeds; but limited accuracy during free-living conditions when
      worn at non-traditional wearing positions (necklace and pants pocket).
      Reliability was acceptable during treadmill walking at higher speeds and free
      living conditions.

PMID- 22483531
TI  - Prevalence of alcohol and other psychoactive substances in injured drivers:
      comparison between Belgium and The Netherlands.
AB  - STUDY OBJECTIVE: To compare the prevalence of alcohol and (il)licit drugs in
      seriously injured drivers in Belgium (BE) and the Netherlands (NL). METHODS:
      Injured car and van drivers admitted to the emergency departments of five
      hospitals in Belgium and three in the Netherlands from January 2008 to May 2010
      were included. Blood samples were taken and analysed for ethanol (with an
      enzymatic method) and 22 other psychoactive substances (UPLC-MS/MS or GC-MS).
      RESULTS: In total 535 injured drivers were included in the study (BE: 348; NL:
      187). More drivers were found positive for alcohol and drugs in Belgium (52.6%)
      than in the Netherlands (33.9%). Alcohol (>=0.1 g/L) was the most prevalent
      substance in both countries (BE: 42.5%; NL: 29.6%). A similar prevalence was
      found for amphetamine (BE: 2.6%; NL: 2.2%) and cocaine (BE: 2.3%; NL: 2.1%). In
      the Netherlands almost no positive findings for cannabis were recorded (0.5%). No
      driver tested positive for benzodiazepines in the Netherlands compared to 7.3% in
      Belgium. More injured drivers tested positive for Z-drugs (BE: 1.8%; NL: 0.5%)
      and medicinal opioids (BE: 3.3%; NL: 0.5%) in Belgium. CONCLUSIONS: The
      prevalence of alcohol in seriously injured drivers was 12% higher found in
      Belgium than in the Netherlands. The prevalence of drugs was similar in both
      countries except for THC and medicinal drugs, particularly benzodiazepines, with
      a much higher prevalence in Belgium. In comparison to previous survey there were
      differences in the prevalence of THC, benzodiazepines and combinations of drugs.
      Possible explanations are the different matrix used, a bias in study population,
      or in case of illicit opiates and benzodiazepines a different consumption pattern
      in the two countries. Alcohol is still the most prevalent substance among the
      injured driver population and this increased the last 15 years.

PMID- 22483532
TI  - [The role of endovascular treatment in chronic mesenteric ischemia].

PMID- 22483533
TI  - [Bioethics limitation of therapeutic effort in pediatrics].
AB  - Given that the demand of society has shifted to seek maximum efficiency, maximum
      help based on the patient autonomy respect and awareness of its necessity, the
      limitation of therapeutic effort is one of the decisions more complex. Therefore,
      it should be an institutional objective to know the limitations of practice,
      assess and encourage improvement and in doubtful cases, resort to Assistive
      Bioethics Committees to advise on the development of clinical protocols in cases
      which the professional or the therapeutic team is faced with an ethical dilemma.

PMID- 22483534
TI  - The challenge to bring personalized cancer medicine from clinical trials into
      routine clinical practice: the case of the Institut Gustave Roussy.
AB  - Research with high throughput technologies has propitiated the segmentation of
      different types of tumors into very small subgroups characterized by the presence
      of very rare molecular alterations. The identification of these subgroups and the
      apparition of new agents targeting these infrequent alterations are already
      affecting the way in which clinical trials are being conducted with an increased
      need to identify those patients harboring specific molecular alterations. In this
      review we describe some of the currently ongoing and future studies at the
      Institut Gustave Roussy that aim for the identification of potential therapeutic
      targets for cancer patients with the incorporation of high throughput
      technologies into daily practice including aCGH, next generation sequencing and
      the creation of a software that allows for target identification specific for
      each tumor. The initial intention is to enrich clinical trials with cancer
      patients carrying certain molecular alterations in order to increase the
      possibility of demonstrating benefit from a targeted agent. Mid and long term
      aims are to facilitate and speed up the process of drug development as well as to
      implement the concept of personalized medicine.

PMID- 22483536
TI  - [University hospitals in Spain: do we understand their concept and function?].

PMID- 22483535
TI  - Medullary circuits for nociceptive modulation.
AB  - Neurons in the medullary raphe are critical to opioid analgesia through
      descending projections to the dorsal horn. Work in anesthetized rats led to the
      postulate that nociceptive suppression results from tonic activation of
      nociceptive-inhibiting neurons and tonic inhibition of nociceptive-facilitating
      neurons. However, morphine does not cause tonic changes in raphe neuronal firing
      in unanesthetized rodents. Recent work suggests that a drop in activity of
      nociceptive-inhibiting neurons synchronizes nociceptive circuits and a burst of
      activity in nociceptive-facilitating neurons facilitates withdrawal magnitude.
      After morphine, the phasic responses of raphe cells are suppressed along with
      nociceptive withdrawals. The results suggest a new model of brainstem modulation
      of nociception in which the medullary raphe facilitates nociceptive reactions
      when noxious input occurs and may modulate other functions between injurious
      events.

PMID- 22483537
TI  - [Mycophenolate mofetil: an alternative treatment for refractory autoimmune
      hemolytic anemia in children].

PMID- 22483538
TI  - Electroclinical overlap of two types of epileptic encephalopathy occurring in the
      same children in a certain age period?
AB  - In this study, we describe three patients who each had an electroclinical overlap
      of two different epileptic encephalopathies (EE), with onset in a certain age
      period. Patient 1 had electroclinical features compatible with continuous spikes
      and waves during slow sleep (CSWSS) syndrome that changed into Lennox-Gastaut
      syndrome (LGS) (symptomatic, cause porencephalic cyst) at the age of 8.5 years.
      Patient 2 had LGS which evolved into CSWSS at the age of 6 years (symptomatic,
      cause polymicrogyria). The third patient had cryptogenic CSWSS syndrome at age
      the age of 7 years which evolved into LGS at the age of 7.5 years. All three
      patients could be considered to have two EE: CSWSS syndrome and LGS or to have
      had overlapping features of these epileptic syndromes.

PMID- 22483539
TI  - Anticonvulsant effect of retigabine during postnatal development in rats.
AB  - Retigabine is a new-generation antiepileptic drug that exerts therapeutic action
      through the activation of KCNQ channel dependent M-type potassium currents. While
      retigabine has been extensively studied in adult animals using a wide variety of
      seizure models, its effects in developing animals have not been examined. There
      has only been one previous report of retigabine efficacy in juvenile rats
      (Mazarati et al., 2008), which examined efficacy against kindled seizures and did
      not examine ages younger than postnatal day (P) 14. To determine the efficacy of
      retigabine during brain development we pretreated rats with retigabine (0-30
      mg/kg) at three ages corresponding to the neonatal period through late
      childhood/early adolescence (i.e., P7, P14, or P25). Seizures were induced 30 min
      later using a chemoconvulsant (pentylenetetrazol, PTZ) model, which has been
      widely used to determine anticonvulsant efficacy of many other antiepileptic
      drugs in neonatal animals. In a dose and age-dependent manner, retigabine reduced
      the severity of PTZ evoked seizures, increased the latency to seizure onset, and
      decreased the incidence of full maximal seizures. The minimum effective dose was
      found to be 5mg/kg for P7 animals, 2.5mg/kg for P14 animals, and 1mg/kg for P25
      animals. These findings allow a direct comparison between retigabine and
      previously studied antiepileptic drugs against PTZ seizures during development,
      and provide the first report of the effective dose range of retigabine in
      neonatal animals.

PMID- 22483540
TI  - The haemodynamic response to pre-hospital RSI in injured patients.
AB  - BACKGROUND: Laryngoscopy and tracheal intubation provoke a marked sympathetic
      response, potentially harmful in patients with cerebral or cardiovascular
      pathology or haemorrhage. Standard pre-hospital rapid sequence induction of
      anaesthesia (RSI) does not incorporate agents that attenuate this response. It is
      not known if a clinically significant response occurs following pre-hospital RSI
      or what proportion of injured patients requiring the intervention are potentially
      at risk in this setting. METHODS: We performed a retrospective analysis of 115
      consecutive pre-hospital RSI's performed on trauma patients in a physician-led
      Helicopter Emergency Medical Service. Primary outcome was the acute haemodynamic
      response to the procedure. A clinically significant response was defined as a
      greater than 20% change from baseline recordings during laryngoscopy and
      intubation. RESULTS: Laryngoscopy and intubation provoked a hypertensive response
      in 79% of cases. Almost one-in-ten patients experienced a greater than 100%
      increase in mean arterial pressure (MAP) and/or systolic blood pressure (SBP).
      The mean (95% CI) increase in SBP was 41(31-51) mmHg and MAP was 30(23-37) mmHg.
      Conditions leaving the patient vulnerable to secondary injury from a hypertensive
      response were common. CONCLUSIONS: Laryngoscopy and tracheal intubation,
      following a standard pre-hospital RSI, commonly induced a clinically significant
      hypertensive response in the trauma patients studied. We believe that, although
      this technique is effective in securing the pre-hospital trauma airway, it is
      poor at attenuating adverse physiological effects that may be detrimental in this
      patient group.

PMID- 22483541
TI  - Below-elbow cast for metaphyseal both-bone fractures of the distal forearm in
      children: a randomised multicentre study.
AB  - INTRODUCTION: Minimally displaced metaphyseal both-bone fractures of the distal
      forearm in children are often treated with an above-elbow cast (AEC). Treatment
      with a below-elbow cast (BEC) could give more comfort, but might lead to fracture
      displacement reducing pronation and supination. Because this has not been
      systematically investigated, we set up a randomised multicentre study. The
      purpose of this study was to find out whether BEC causes equal limitation of
      pronation and supination but with higher comfort level, compared with AEC.
      PATIENTS AND METHODS: In four hospitals, consecutive children aged<16 (mean 7.1)
      years with a minimally displaced metaphyseal both-bone fracture of the distal
      forearm were randomised to 4 weeks BEC (n=35) or 4 weeks AEC (n=31). Primary
      outcome was limitation of pronation and supination 6 months after initial trauma.
      The secondary outcomes were cast comfort, limitation of flexion/extension of
      wrist/elbow, complications, cosmetics, complaints, and radiological assessment.
      RESULTS: A group of 35 children received BEC and 31 children received AEC. All
      children attended for the final examination at a mean follow-up of 7.0 months
      (range 5.0-11.6 months). Limitation of pronation and supination 6 months after
      initial trauma showed no significant difference between the two groups [4.4
      degrees  (+/- 5.8) for BEC and 5.8 degrees  (+/- 9.8) for AEC]. Children treated
      with BEC had significantly higher cast comfort on a visual analogue scale [5.6
      (+/- 2.7) vs. 8.4 (+/- 1.4)] and needed significantly less help with dressing
      (8.2 days vs. 15.1 days). Six complications occurred in the BEC group and 14 in
      the AEC group. Other secondary outcomes were similar between the two groups.
      CONCLUSIONS: Children with minimally displaced metaphyseal both-bone fractures of
      the distal forearm should be treated with a below-elbow cast.

PMID- 22483542
TI  - Long-term functional outcome following intramedullary nailing of femoral shaft
      fractures.
AB  - BACKGROUND: The management of femoral shaft fractures using intramedullary
      nailing is a popular method. The purpose of this study was to evaluate the long
      term functional outcome after antegrade or retrograde intramedullary nailing of
      traumatic femoral shaft fractures. We further determined predictors of these
      functional outcome scores. METHODS: In a retrospective study, patients with a
      femoral shaft fracture but no other injuries to the lower limbs or pelvis were
      included. A total of 59 patients met the inclusion criteria. Functional outcome
      scores (Short Musculoskeletal Functional Assessment (SMFA), Western Ontario and
      McMaster University Osteoarthritis (WOMAC) index, Harris Hip Score (HHS) and the
      Lysholm knee function scoring scale) were measured at a mean of 7.8 years (+/-
      3.5 years) postoperatively. The Visual Analogue Scale (VAS) was used to determine
      pain complaints of the lower limb. RESULTS: The range of motion (ROM) of the hip
      and knee joints was comparable between the injured and uninjured leg, regardless
      of the nailing technique. Correlation between ROM and the final outcome scores
      was found to be fair to moderate. Even years after surgery, 17% of the patients
      still reported moderate to severe pain. A substantial correlation was observed
      between VAS and the patient-reported outcome scores. The most significant
      predictor of functional outcome was pain in the lower limb. CONCLUSIONS: Our
      findings suggest that the ROM of hip and knee returns to normal over time,
      regardless of the nailing method used. However, pain in the lower limb is an
      important predictor and source of disability after femoral shaft fractures, even
      though most patients achieved good functional outcome scores.

PMID- 22483544
TI  - Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic
      renal cell carcinoma: incidence, radiographic findings and correlation with
      clinical outcome.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are approved for use
      in patients with metastatic renal cell carcinoma (mRCC) and are under
      investigation in several other malignancies. We assessed the incidence, clinical
      presentation and computed tomography (CT) findings of pneumonitis associated with
      mTOR inhibitors in mRCC. Correlation between radiological findings of pneumonitis
      and clinical outcome was also determined. METHODS: We retrospectively reviewed
      the clinical data and serial CT scans from patients with mRCC treated with either
      temsirolimus or everolimus. Serial chest CT scans were reviewed in consensus,
      read by two independent radiologists for the presence of pneumonitis, and
      corresponding clinical data were reviewed for symptoms and clinical outcome. The
      baseline and follow up CTs were reviewed to assess outcome to therapy. RESULTS:
      The study population consisted of 46 pts, 21 treated with temsirolimus and 25
      with everolimus (M:F 2.5:1; median 63 years, range 31-79 years). CT evidence of
      pneumonitis was seen in 14/46 pts (30%), at a median of 56days on mTOR inhibitor
      treatment (range 31-214 days). Respiratory symptoms at the time of
      radiographically detected pneumonitis, were observed in 7pts. Stable disease (SD)
      by Response Evaluation Criteria in Solid Tumours (RECIST) was achieved in 12/14
      pts (86%) who developed radiographic pneumonitis compared to 14/32 (44%) without
      pneumonitis (p=0.01) The mean change of tumour long axis size for target lesions
      by RECIST, normalised for 30 days on therapy was -2.9% in the pneumonitis group
      and +4.3% in the non-pneumonitis group (p=.002). CONCLUSIONS: Preliminary data
      suggest that pneumonitis may be a marker of stable disease by RECIST and
      therefore, of therapeutic benefit. Careful patient assessment should be
      undertaken before the drug is discontinued.

PMID- 22483545
TI  - Grape variety related trans-resveratrol induction affects Aspergillus carbonarius
      growth and ochratoxin A biosynthesis.
AB  - The paper reports the results of a study performed to investigate the influence
      of the grape variety on the growth of Aspergillus carbonarius on grape berries
      and the correlation between the amount of ochratoxin A (OTA) and the content of
      trans-resveratrol produced after fungal contamination. Variations in the amount
      of OTA produced by the fungus are observed depending on both grape variety and on
      the induction of trans-resveratrol determined during the infection. The obtained
      data suggest that if an increase in trans-resveratrol production in grape berries
      occurs early after the fungal infection, the berry exploits this compound to
      control OTA synthesis. If the increase in trans-resveratrol concentration is
      delayed after fungal infection (40 h), a control of OTA accumulation can not be
      achieved. The possibility of exerting significant control of OTA biosynthesis by
      this phytoalexin seems to rely in the promptness of its production, as occurs
      also in other fungus plant interactions and, in turn, seems to be dependent also
      on grape cultivar. In this fungus-plant system, trans-resveratrol appears to
      represent a defence-related compound toward A. carbonarius and OTA contamination.

PMID- 22483546
TI  - Feedforward postural control in individuals with multiple sclerosis during load
      release.
AB  - The aim of the present study was to investigate the organization of anticipatory
      postural adjustments (APAs) in individuals with multiple sclerosis (MS) during
      self-initiated perturbation in the sagittal plane. Eleven individuals with MS and
      eleven age-and-gender matched healthy controls were asked to hold a 2.27 kg load
      in the extended arms and release it using fast arm abduction movements.
      Electrical activity of six leg and trunk muscles as well as displacements of the
      center of pressure (COP) were recorded. The results indicate that individuals
      with MS (1) demonstrate a reduced magnitude of APAs, (2) delayed latency of APAs
      and (3) smaller anticipatory COP displacement as compared to healthy control
      subjects. Moreover, in spite of individuals with MS being mildly affected, their
      balance capacity was significantly diminished. Thus, the outcome of this study
      demonstrates the underlying impairment in anticipatory postural control of
      individuals with MS and provides a background for development of rehabilitation
      strategies focused on balance restoration in this population.

PMID- 22483547
TI  - Enhancing cognitive control components of insight problems solving by anodal tDCS
      of the left dorsolateral prefrontal cortex.
AB  - BACKGROUND: Executive functions play a vital role in semantic processing.
      Recently, transcranial direct current stimulation (tDCS) over frontal regions
      associated with cognitive control has been found to enhance verbal insight
      problem solving. The aim of the current study was to extend our understanding of
      the cognitive control processes modulating verbal insight problem solving.
      HYPOTHESES: Anodal stimulation over the left Dorsolateral Prefrontal Cortex
      (DLPFC) was predicted to improve performance in solving insight problems.
      Particularly, it was expected that this effect would be focused on solution
      recognition, which is hypothesized to be directly related to control processes,
      and would be more pronounced for difficult problems, hypothesized to require more
      cognitive demand. Moreover, we predicted that this effect would be modulated by
      approach motivation tendencies, due to cognition and motivation interactions in
      the DLPFC. METHODS: 21 participants performed a verbal insight problem task
      twice, once under active anodal tDCS over the left DLPFC and once under sham
      stimulation, with a one week interval between sessions. Participants had 7 s to
      generate a solution for each problem, and then were requested to indicate whether
      a target word was the correct solution or not. RESULTS: Stimulation significantly
      enhanced solution recognition for difficult problems. This effect was modulated
      by trait motivation, i.e. was larger for participants with lower approach
      motivation. No effects were found for easy problems, or solution generation.
      CONCLUSIONS: Left DLPFC executive control modulates semantic processing of verbal
      insight problems. The observed synergy between language, cognition and motivation
      carries theoretical implication as well as practical consideration for future
      stimulation research.

PMID- 22483549
TI  - The natural history of primary temporal bone myxoma.
AB  - Primary myxomas of the temporal bone are rare tumors. If misdiagnosed, they can
      grow into locally aggressive expansile masses resulting in hearing loss, facial
      paralysis, dural invasion, and mass effect on the adjacent brain parenchyma. This
      case demonstrates the natural history of an extraordinarily rare tumor over a
      longer period not previously described. The importance of correlating
      histopathologic findings with diagnostic imaging features to enable an accurate
      diagnosis is also emphasized.

PMID- 22483548
TI  - Frontal and parietal theta burst TMS impairs working memory for visual-spatial
      conjunctions.
AB  - In tasks that selectively probe visual or spatial working memory (WM) frontal and
      posterior cortical areas show a segregation, with dorsal areas preferentially
      involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object
      identity) WM. In a previous fMRI study [1], we showed that right parietal cortex
      (PC) was more active during WM for orientation, whereas left inferior frontal
      gyrus (IFG) was more active during colour WM. During WM for colour-orientation
      conjunctions, activity in these areas was intermediate to the level of activity
      for the single task preferred and non-preferred information. To examine whether
      these specialised areas play a critical role in coordinating visual and spatial
      WM to perform a conjunction task, we used theta burst transcranial magnetic
      stimulation (TMS) to induce a functional deficit. Compared to sham stimulation,
      TMS to right PC or left IFG selectively impaired WM for conjunctions but not
      single features. This is consistent with findings from visual search paradigms,
      in which frontal and parietal TMS selectively affects search for conjunctions
      compared to single features, and with combined TMS and functional imaging work
      suggesting that parietal and frontal regions are functionally coupled in tasks
      requiring integration of visual and spatial information. Our results thus
      elucidate mechanisms by which the brain coordinates spatially segregated
      processing streams and have implications beyond the field of working memory.

PMID- 22483550
TI  - How much formalin is enough to fix tissues?
AB  - A total of sixty samples from human breast, uterus, liver, skin and abdominal fat
      were fixed for 8; 24 and 48 hours at a room temperature of 20 to 22 degrees C
      with neutral buffered formalin (NBF) with volume to tissue ratios of 1:1; 2:1;
      5:1 and 10:1 and manually processed with isopropyl alcohol and mineral oil
      mixtures. All the slides prepared were evaluated as suitable for diagnostic
      purposes by nine pathologists from three different Russian histopathology
      institutions. The microtomy quality differences between the samples was not
      statistically significant for the different fixation volume ratios tested, but
      the differences between fixation periods and tissues types were, with 48 hours
      being the optimum fixation period, with skin and fat the most difficult to
      infiltrate. Neither the time and volume ratio combinations affected the pH of NBF
      or the immunostaining for vimentin in uterus or the histochemical periodic acid
      reaction or reticular demonstration fibers in liver. Fixing tissues with a ratio
      of NBF volume to tissue volume of 2:1 for 48 hours at 20-22 degrees C was enough
      to assure a proper fixation and infiltration of the tested tissues and there is
      no objective reason to expect that other tissues will not behave similarly. It is
      suggested that in order to obtain good fixation and paraffin wax infiltration in
      around 10 hours, the fixation with NBF at 2:1 should be at 45 degrees C with
      pressure and agitation.

PMID- 22483551
TI  - Healthy supermarkets: zoning for healthy food choices.

PMID- 22483552
TI  - Cardioprotective effect of total paeony glycosides against isoprenaline-induced
      myocardial ischemia in rats.
AB  - Paeoniae radix is a traditional Chinese medicinal herb for treating some
      diseases; important components are total paeony glycosides (TPGs), an approved
      drug by the State Food and Drug Administration (SFDA) for the therapy of
      rheumatoid arthritis (RA). We firstly reported myocardial benefits of TPGs
      previously, and the present study is to further investigate the underlying
      mechanisms for preventing oxidative damage in cardiomyopathy. We measured the
      capacity of TPGs to scavenge free radicals in vitro. Then 60 SD rats were
      randomly divided into five groups: (1) a normal control group, (2) an
      isoprenaline (ISO)-induced myocardial ischemic model group, (3) a TPG treatment
      group (TPGs 269.4 mg/kg delivered by intragastric administration for 3 days
      before ISO administration and TPGs 449 mg/kg delivered for 3 days after ISO
      administration), (4) a TPG therapy group (TPGs 449 mg/kg delivered for 3 days
      after ISO administration), and (5) a positive control group (propranolol 15 mg/kg
      for 3 days after ISO administration). The ISO-induced myocardial ischemic model
      was established by subcutaneous injection of 1mg/kg/8h ISO (2 times). The
      activities of myocardial enzymes, including glutamic oxaloacetic transaminase
      (GOT), creatine kinase (CK), lactate dehydrogenase (LDH), antioxidant enzyme
      superoxide dismutase (SOD) as well as the content of lipid peroxidation product
      malondialdehyde (MDA) were detected. We found that TPGs potently eliminated
      hydroxyl radicals and superoxide in vitro using ESR assays. Compared with model
      rats, TPG treatment, TPG therapy and the positive control treatment exhibited
      significantly reduced activities of GOT, LDH, and CK (p < 0.01), increased
      activity of SOD (p < 0.01) and lower levels of MDA (p < 0.05). More
      interestingly, the protective effect of TPG treatment was even better than that
      of propranolol. These results suggest that TPGs significantly ameliorate ISO
      induced myocardial ischemia and their action might be through reducing oxidative
      stress in ischemic myocardium.

PMID- 22483553
TI  - Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma
      A549/DDP cell apoptosis through HIF-1alpha and caspase-3 mechanisms.
AB  - Curcumin, a yellow pigment derived from Curcuma longa Linn, has been favored by
      the Eastern as dietary ingredients for centuries. During the past decade,
      extensive investigations have revealed curcumin sensitized various
      chemotherapeutic agents in human breast, colon, pancreas, gastric, liver, brain
      and hematological malignant disorders in vivo and in vitro. Several pathways and
      specific targets including NF-kappaB, STAT3, COX-2, Akt and multidrug resistant
      protein have been identified to facilitate curcumin as a chemosensitizer. Recent
      studies suggest HIF-1alpha participated in the development of drug resistance in
      cancer cells and targeting HIF-1alpha either by RNAi or siRNA successfully
      overcame chemotherapeutic resistance. To investigate the mechanism basis of
      curcumin as a chemosensitizer in lung cancer, we examined curcumin's effects on
      HIF-1alpha in cis-platin (DDP) sensitive A549 and resistant A549/DDP cell lines
      by RT-PCR and Western blot. HIF-1alpha in A549/DDP cells was found to be
      overexpressed at both mRNA and protein levels together with a poor response to
      DDP. Results from transient transfection and flow cytometry showed the HIF-1alpha
      abnormality contributed to DDP resistance in A549/DDP lung cancer cells. Combined
      curcumin and DDP treatment markedly inhibited A549/DDP cells proliferation,
      reversed DDP resistance and triggered apoptotic death by promoting HIF-1alpha
      degradation and activating caspase-3, respectively. Expression of HIF-1alpha
      dependent P-gp also seemed to decrease as response to curcumin in a dose
      dependent manner. Our findings shed light on drug resistant reversing effect of
      curcumin in lung cancer cells by inhibiting HIF-1alpha expression and activating
      caspase-3.

PMID- 22483554
TI  - Polydatin protects learning and memory impairments in a rat model of vascular
      dementia.
AB  - Polydatin is one of the most common encountered stilbenes of nature and a key
      component of the Chinese herb Polygonum cuspidatum. This study is to investigate
      the effects of polydatin on learning and memory impairments induced by chronic
      cerebral hypoperfusion in rats, as well as the potential mechanism. Both common
      carotid arteries and both vertebral arteries occlusion (four-vessel occlusion, 4
      VO) induced severe cognitive deficits tested by water maze task, along with
      oxidative stress in hippocampus. Oral administration of polydatin for 30 days
      markedly attenuated cognitive deficits compared with the control (p < 0.05).
      Biochemical determination revealed that polydatin decreased the production of
      malondialdehyde (MDA) and significantly increased the activities of superoxide
      dismutase (SOD) and catalase (CAT). Additionally, polydatin effectively
      alleviated the injuries of cultured neurons induced by oxygen-glucose deprivation
      (OGD). These results suggest that polydatin exhibit therapeutic potential for
      vascular dementia, which is most likely related, at least in part, to its anti
      oxidant activity and the direct protection of neurons.

PMID- 22483555
TI  - Ameliorative effect of berberine on renal damage in rats with diabetes induced by
      high-fat diet and streptozotocin.
AB  - Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has
      widely been used for the treatment of diabetic nephropathy. The aims of the study
      were to investigate the effects and mechanism of action of berberine on renal
      damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a
      high-fat diet and intraperitoneal injection of 40 mg/kg streptozotocin (STZ).
      Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated
      diabetic rats iii) 250 mg/kg metformin-treated, iv and v) 100 and 200 mg/kg
      berberine-treated diabetic rats and treated separately for 8 weeks. The fasting
      blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin
      were measured in rats. Kidneys were isolated at the end of the treatment for
      histology, Western blot analysis and estimation of malonaldehyde (MDA),
      superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The
      results revealed that berberine significantly decreased fasting blood glucose,
      insulin levels, total cholesterol, triglyceride levels, urinary protein
      excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats.
      The histological examinations revealed amelioration of diabetes-induced
      glomerular pathological changes following treatment with berberine. In addition,
      the protein expressions of nephrin and podocin were significantly increased. It
      seems likely that in rats berberine exerts an ameliorative effect on renal damage
      in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms
      for the renoprotective effects of berberine may be related to inhibition of
      glycosylation and improvement of antioxidation that in turn upregulate the
      expressions of renal nephrin and podocin.

PMID- 22483556
TI  - Evolution of lymphoid tissues.
AB  - Lymphoid organs are integral parts of all vertebrate adaptive immune systems.
      Primary lymphoid tissues exhibit a remarkable functional dichotomy: T cells
      develop in specialized thymopoietic tissues located in the pharynx, whereas B
      cells develop in distinct areas of general hematopoietic areas, such as the
      kidney or bone marrow. Among secondary lymphoid tissues, the spleen is present in
      all vertebrates, whereas lymph nodes represent an innovation particular to
      mammals and some birds. A comparative analysis of anatomical, functional and
      genomic features thus reveals the core components of adaptive immune systems.
      Such information has guided recent attempts at reconstructing lymphopoietic
      functions in vivo and in the future might inspire the development of new
      strategies for medical interventions restoring and modulating immune functions.

PMID- 22483557
TI  - High prevalence and genotypes of Toxoplasma gondii isolated from organic pigs in
      northern USA.
AB  - The ingestion of undercooked pork infected with Toxoplasma gondii is considered
      an important source of transmission of this parasite. While T. gondii infection
      in confinement raised market pigs (market pigs are typically used for fresh,
      unprocessed pork products) in the USA has decreased significantly over the last
      20 years, infection levels in pigs with access to the outdoors can be quite high.
      An upsurge in consumer demand for 'organically raised', 'humanely raised' and
      'free range' pork products has resulted in increasing numbers of hogs being
      raised in non-confinement systems. To determine T. gondii infection rate in these
      organic pigs, prevalence of T. gondii in organically raised pigs in two
      establishments (Farm 1, Farm 2) in Michigan was investigated. Serum and tissue
      samples from 33 pigs on the farm were available for T. gondii evaluation at
      slaughter. Serological testing was performed using both ELISA and the modified
      agglutination test (MAT). Antibodies to T. gondii were detected by both ELISA and
      MAT in 30 of 33 animals with MAT titers of 1:25 in three, 1:50 in six, 1:100 in
      seven, 1:200 in 13, and 1:400 in one. Hearts of all 33 pigs were bioassayed for
      T. gondii in mice; T. gondii was isolated from 17 pigs including one from a
      seronegative (both ELISA and MAT) pig. Genetic typing of 16 of the 17 T. gondii
      isolates using the SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and
      Apico loci revealed clonal Type II from Farm 1 and clonal Type III on Farm 2.
      These results revealed very high prevalence of T. gondii in organic pigs for the
      first time in USA, indicating potentially increased health risk of consuming
      organic swine products.

PMID- 22483558
TI  - Production of biofuels from pretreated microalgae biomass by anaerobic
      fermentation with immobilized Clostridium acetobutylicum cells.
AB  - The purpose of this work was to study the possible use of pretreated biomass of
      various microalgae and cyanobacteria as substrates for acetone-butanol-ethanol
      (ABE) fermentation by Clostridium acetobutylicum cells immobilized into
      poly(vinyl alcohol) cryogel. To this end, the biochemical composition of
      photosynthetic microorganisms cultivated under various conditions was studied.
      The most efficient technique for pretreating microalgal biomass for its
      subsequent conversion into biofuels appeared to be thermal decomposition at 108 
      degrees C. For the first time the maximum productivity of the ABE fermentation in
      terms of hydrogen (8.5 mmol/L medium/day) was obtained using pretreated biomass
      of Nannochloropsis sp. Maximum yields of butanol and ethanol were observed with
      Arthrospira platensis biomass used as the substrate. Immobilized Clostridium
      cells were demonstrated to be suitable for multiple reuses (for a minimum of five
      cycles) in ABE fermentation for producing biofuels from pretreated microalgal
      biomass.

PMID- 22483559
TI  - Characterization of biochars to evaluate recalcitrance and agronomic performance.
AB  - Biochars (n=94) were found to have ash contents from 0.4% to 88.2%, volatile
      matter from 13.2% to 70.0%, and fixed carbon from 0% to 77.4% (w/w). Greater
      pyrolysis temperature for low-ash biochars increased fixed carbon, but decreased
      it for biochars with more than 20% ash. Nitrogen recovery varied depending on
      feedstock used to a greater extent (12-68%) than organic (25-45%) or total C (41
      76%) at a pyrolysis temperature of 600  degrees C. Fixed carbon production ranged
      from no enrichment in poultry biochar to a 10-fold increase in corn biochar (at
      600  degrees C). Prediction of biochar stability was improved by a combination of
      volatile matter and H:C ratios corrected for inorganic C. In contrast to
      stability, agronomic utility of biochars is not an absolute value, as it needs to
      meet local soil constraints. Woody feedstock demonstrated the greatest
      versatility with pH values ranging from 4 to 9.

PMID- 22483560
TI  - Emergence of a novel multidrug-resistant Pseudomonas aeruginosa strain producing
      IMP-type metallo-beta-lactamases and AAC(6')-Iae in Japan.
AB  - The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa isolates
      producing IMP-type metallo-beta-lactamases (MBLs) and aminoglycoside 6'-N
      acetyltransferase [AAC(6')-Iae] has become a serious problem in medical settings
      in Japan. A total of 217 MDR P. aeruginosa isolates were obtained from August
      2009 to April 2010 from patients at 144 hospitals in Japan, of which 145 (66.8%)
      were positive for IMP-type MBLs and AAC(6')-Iae when tested with an
      immunochromatographic assay. Polymerase chain reaction (PCR) showed that these
      isolates were also positive for blaIMP and aac(6')-Iae genes. When these IMP-type
      MBL- and AAC(6')-Iae-producing isolates were analysed by pulsed-field gel
      electrophoresis (PFGE), two clusters (I and II) were detected. Most of the
      isolates (88.3%; 128/145) were grouped under cluster I and had multilocus
      sequence type ST235 and serotype O11, except for one isolate that was ST991 and
      serotype O3. The isolates were mainly isolated from the urinary tract (82/145;
      56.6%) and respiratory tract (58/145; 40.0%). The epidemiological properties of
      the isolates belonging to cluster I were similar to those of MDR P. aeruginosa
      isolates that have been previously reported in Japan. The remaining 16 isolates
      belonged to cluster II, had identical PFGE patterns and were multilocus sequence
      type ST991 and serotype O18; all of these isolates were isolated from the
      respiratory tract. The properties of isolates belonging to cluster II have not
      been previously described, indicating that a novel IMP-type MBL- and AAC(6')-Iae
      producing P. aeruginosa strain is emerging in Japan. Isolates belonging to both
      clusters were isolated from different parts of the country.

PMID- 22483561
TI  - 2-Hydroxyisocaproic acid (HICA): a new potential topical antibacterial agent.

PMID- 22483562
TI  - What's behind the failure of emerging antibiotics in the critically ill?
      Understanding the impact of altered pharmacokinetics and augmented renal
      clearance.

PMID- 22483563
TI  - [Septic pulmonary embolism after removal of a venous access device for septic
      thrombophlebitis].
AB  - Septic thrombophlebitis on a central venous access device (CVAD) is a rare and
      serious complication. According to current guidelines, the device should be
      removed and antibiotics be given. The risk of septic thrombophlebitis is related
      to the migration of septic emboli to the lung, a potentially fatal event,
      particularly in frail patients with lung cancer. We report a case observed in a
      66-year-old man with multiple metastatic lung cancer who had a CVAD and who
      developed septic thrombophlebitis leading to coagulase-negative staphylococcal
      bacteriemia. After removal of the CVAD, the thrombophlebitis was complicated by
      pulmonary embolism affecting the entire network of the right lung.

PMID- 22483564
TI  - [In utero fetal programming and its impact on health in adulthood].
AB  - Adverse events during intrauterine life may program organ growth and favor
      disease later in life. This is the usually called 'Barker's hypothesis'.
      Increasing evidence suggests that conditions like vascular disease, hypertension,
      metabolic syndrome, and type 2 diabetes mellitus are programmed during the early
      stages of fetal development and become manifest in late stages of life, when
      there is an added impact of lifestyle and other conventional acquired
      environmental risk factors that interact with genetic factors. The aim of this
      review was to provide additional, updated evidence to support the association
      between intrauterine fetal health and increased prevalence of chronic non
      communicable diseases in adulthood. Various potential cellular and molecular
      mechanisms proposed to be related to the above hypothesis are discussed,
      including endothelial function, oxidative stress, insulin resistance, and
      mitochondrial function.

PMID- 22483565
TI  - Serum bilirubin levels and the risk of Crohn's disease.

PMID- 22483566
TI  - Effectiveness of contrast-enhanced ultrasound for characterisation of intestinal
      inflammation in Crohn's disease: a comparison with surgical histopathology
      analysis.
AB  - BACKGROUND: Differentiation between predominantly inflammatory versus fibrous
      predominant lesions is particularly important in order to decide the optimal
      therapy in patients with refractory symptoms in Crohn's disease (CD). OBJECTIVE:
      The purpose of this investigation was to evaluate the accuracy of several US
      parameters, especially of contrast-enhanced US, for evaluation of mural
      inflammation in CD, with histopathology as the reference. MATERIALS AND METHODS:
      Preoperative ultrasound examination, including contrast-enhanced ultrasound
      (CEUS) was performed in 25 consecutive patients with Crohn's disease undergoing
      elective bowel resection. Ultrasound variables, such as wall thickness,
      transmural complications, colour Doppler grade, quantitative analysis of the
      enhancement and the presence and severity of strictures, were prospectively
      evaluated and compared with the histopathology results. Histopathology grading of
      acute inflammation using the acute inflammatory score and the degree of
      fibrostenosis was performed in each segment and the results were compared with
      all the US variables as well as with a previously defined ultrasound score system
      for inflammatory and fibrostenotic changes. RESULTS: 28 segments were analysed.
      In pathology analysis there were 12 predominantly inflammatory segments, 9
      predominantly fibrostenotic and 7 compound lesions. When the pathology score was
      dichotomised into two groups (inflammatory and fibrostenotic) the number of
      stenoses correctly classified by US was 23 out 28, with a substantial agreement
      (kappa=0.632). There was a good correlation between the sonographic and pathology
      scores, both inflammation (Spearman's, r=0.53) and fibrostenosis (Spearman's,
      r=0.50). Transmural complications, colour Doppler grade and percentage of
      increase in contrast enhancement were significantly associated with the pathology
      inflammatory score (p=0.018, p=0.036 and p=0.005, respectively). There was a
      significantly negative association between the colour Doppler grade and the
      pathologic fibrostenotic score. CONCLUSIONS: Ultrasound, including CEUS, can be a
      useful tool for distinguishing inflammatory from fibrostenotic lesions in CD.
      This information can be useful in the management of CD.

PMID- 22483567
TI  - Long-term outcome of tumor necrosis factor alpha antagonist's treatment in
      pediatric Crohn's disease.
AB  - BACKGROUND: Anti tumor necrosis factor alpha (TNFalpha) agents have become widely
      used in pediatric inflammatory bowel disease (IBD). So far, only few studies
      examined the long-term results of anti-TNFalpha treatment in children with IBD.
      METHODS: The long-term outcome of pediatric patients with IBD was assessed
      retrospectively in a multicenter cohort of children treated with anti-TNFalpha
      beyond induction treatment. Short- and long-term response rates, predictors for
      loss of response, data on growth and laboratory parameters were assessed.
      RESULTS: 120 patients [101 crohn's disease (CD), 19 ulcerative colitis (UC) or
      indeterminate colitis (IC)] received either infliximab or adalimumab. The mean
      age at initiation of anti-TNFalpha was 13.4 +/- 3.9 years and the median duration
      of anti-TNFalpha treatment was 15 months (range: 2-90). Overall, 89% of the
      cohort experienced short-term response following induction. Response was
      associated with improvement in weight and BMI Z-scores (p<0.001) but not with
      linear growth. Responders experienced a significant decrease in erythrocyte
      sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p<0.001).
      Albumin and hemoglobin both improved but only albumin increased significantly
      (p<0.001). The cumulative probability of losing response to anti-TNFalpha
      treatment was 17%, 38%, and 49% after 1, 3, and 5 years, respectively. Responders
      had a significantly lower weight and BMI Z-scores at initiation of anti-TNFalpha
      treatment in compared to non-responders (p=0.04 and 0.02 respectively).
      CONCLUSIONS: Our long term cohort supports the current evidence on the
      effectiveness and safety of anti-TNFalpha treatment in children with IBD.
      Response to treatment was interestingly associated with lower weight and BMI.

PMID- 22483568
TI  - Risedronate improves bone mineral density in Crohn's disease: a complementary
      mechanism.

PMID- 22483569
TI  - The delignification effects of white-rot fungal pretreatment on thermal
      characteristics of moso bamboo.
AB  - Moso bamboo (Phyllostachys pubesescens) is a major bamboo species which is widely
      used for temporary scaffolding in China. Its fast growing and low ash content
      make moso bamboo a potential renewable energy resource. In present work, thermal
      behaviors of moso bamboo and its lignocellulosic fractions were investigated
      using thermogravimetric analysis. Furthermore, to understand whether the
      delignification effect of white-rot fungi can promote the thermal decomposition
      of bamboo especially the lignin component, the changes in lignocellulose
      components as well as thermal behaviors of bamboo and acid detergent lignin were
      investigated. The results showed that the white-rot fungal pretreatment is
      advantageous to thermal decomposition of lignin in bamboo. The weight losses of
      ADL samples became greater and the thermal processes were accelerated after
      biopretreatment. The total pyrolysis weight loss increased from 57.14% to 65.07%
      for Echinodontium taxodii 2538 treated bamboo ADL sample.

PMID- 22483570
TI  - Effects of Fe(II) and Fe(III) on the single-stage deammonification process
      treating high-strength reject water from sludge dewatering.
AB  - Iron (Fe) is often encountered in wastewaters. This study investigated the
      effects of iron on the single-stage deammonification process treating reject
      water from sludge dewatering. When Fe(2+) and Fe(3+) concentrations in the
      influent were below 1.3mg/L and 0.4 mg/L, Fe(2+) incorporation was found to be
      linearly correlated with NH(4)(+)-N removal. However, the excess Fe(2+) and
      Fe(3+) drastically deteriorated the deammonification performance. Both of the
      reactor performance and Fluorescence In Situ Hybridization results suggested
      higher sensitivity of autotrophic bacteria to iron than heterotrophs, the
      sequence of which was assessed to anammox bacteria>aerobic ammonium
      oxidizers>hetetrophic denitrifiers. With the excess existence of iron,
      extracellular substances were largely released by bacterial cells, which were the
      likely sites for iron uptake by scanning electron microscope-energy dispersive X
      ray analysis. The information provided here would be useful to facilitate the
      application of deammonification process in the treatment of wastewater including
      metal iron.

PMID- 22483571
TI  - The influence of additives (Ca2+, Al3+, and Fe3+) on the interaction energy and
      loosely bound extracellular polymeric substances (EPS) of activated sludge and
      their flocculation mechanisms.
AB  - The activated sludge (AS) flocculability markedly improved after the addition of
      Al(3+) and Fe(3+) compared to Ca(2+) at a concentration of 2 mEq/L. Though the
      energy barrier decreased about 30% when Ca(2+) was added, the AS flocculability
      did not improve substantially. This indicates that extended DLVO theory can
      explain AS flocculation with Al(3+) and Fe(3+) as additives but is not
      appropriate for Ca(2+). In addition, no matter which cation was added, the AS
      flocculability was highly correlated to the loosely bound extracellular polymeric
      substances (LB-EPS) content. The majority of added Ca(2+) remained in the bulk
      solution (about 92%), whereas almost all of the Al(3+) and Fe(3+) added was found
      in the pellet (about 98%). The cation' ability to bind to the AS is closely
      related to the energy barrier and LB-EPS contents, therefore it is the core
      reason behind the AS flocculation changes observed upon the addition of
      multivalent cations.

PMID- 22483572
TI  - New contributions to the ORP & DO time profile characterization to improve
      biological nutrient removal.
AB  - Changes in the oxidation-reduction potential (ORP), pH and dissolved oxygen (DO),
      along with organic load and nutrient removal in a municipal wastewater treatment
      plant (WWTP) have been monitored throughout one year. The "nitrate knee" and the
      "nitrate break point" in ORP profiles, the "nitrate apex" and the "ammonia
      valley" in pH profiles and the "DO elbow" in DO profiles have been identified.
      Furthermore, these bending points have been correlated with the oxygen uptake
      rate (OUR), the temperature in the vessel and the aeration and non-aeration time
      profiles by using Principal Component Analysis (PCA). The data have been
      previously split up into wet and dry weather cycles by means of a K-means
      clustering algorithm. Finally, two new parameters have been defined: the "ORP
      Arrow", which is closely related to the inhibition of the denitrification
      process, and the "Oxygen Rise Average Slope" (ORAS), which shows the oxygen
      transfer rate.

PMID- 22483573
TI  - Sustainable scale-up of active management of the third stage of labor for
      prevention of postpartum hemorrhage in Ecuador.
AB  - OBJECTIVE: To analyze the Ecuadorian experience regarding the adoption, scale-up,
      and institutionalization of active management of the third stage of labor (AMTSL)
      for prevention of postpartum hemorrhage via continuous quality improvement (CQI)
      processes. METHODS: Average AMTSL implementation rates for women with vaginal
      deliveries were compared using unweighted provincial aggregate data from
      facilities participating in 3 phases of AMTSL programming. Months taken to
      implement AMTSL at 80% or more and 90% or more compliance were compared across
      phases. RESULTS: Rate of oxytocin administration during the first 3 months was
      5.0% in phase 1, 9.8% in phase 2, and 72.2% in phase 3 (P<=0.001 vs phases 1 and
      2). The average number of months provinces took to increase oxytocin
      administration to 80% or more and 90% or in more women with vaginal deliveries
      was, respectively, 21.6+/-18.7 and 30.6+/-16.4 in phase 1, 23.5+/-15.1 and 30.1+/
      14.9 in phase 2, and 4.7+/-4.9 (P<=0.01 vs phase 1; P<=0.001 vs phase 2) and
      4.0+/-3.4 (P<=0.001 vs phases 1 and 2) in phase 3. By December 2009, AMTSL
      implementation was sustained at 90% or more in all provinces. CONCLUSION: CQI
      processes identified resistance and operational barriers, and developed
      mechanisms to overcome them.

PMID- 22483574
TI  - Is the post-transplantation treatment with AMD beneficial?
AB  - Recent data have suggested novel ways to enhance donor cell engraftment by
      treating transplanted recipients with CXCR4/CXCL12 inhibitors, thereby expanding
      the biologic potential of these molecules primarily used for mobilization
      purposes. We tested whether repeated pulse inhibitions of CXCR4/CXCL12 signaling
      using AMD, an inhibitor of CXCR4/CXCL12 signaling, would enhance engraftment in
      non-myeloablated murine recipients, similar to data published in a myeloablative
      setting. We documented an increased proportion of circulating neutrophils (both
      donor- and host-derived) in the AMD-treated group, but this increase was not
      kinetically influenced by AMD treatment and multilineage engraftment was not
      enhanced. Although our results with neutrophils are similar to recent clinical
      data in neutropenic patients chronically treated with AMD, the absence of
      multilineage engraftment diverges from data in myeloablated recipients. We
      conclude that pulses of mobilization by AMD post transplantation do not enhance
      multilineage engraftment.

PMID- 22483575
TI  - Mutations of FLVCR1 in posterior column ataxia and retinitis pigmentosa result in
      the loss of heme export activity.
AB  - The feline leukemia virus subgroup C receptor 1 (FLVCR1) is a heme exporter that
      maintains the intracellular heme concentration. FLVCR1 was previously assumed to
      be involved in Diamond-Blackfan anemia, and it was recently reported that
      mutations in the FLVCR1 gene are found in patients with posterior column ataxia
      and retinitis pigmentosa (PCARP). Four mutations in FLVCR1 (Asn121Asp, Cys192Arg,
      Ala241Thr, and Gly493Arg) are located within putative transmembrane domains;
      however, the effects of FLVCR1 mutations on PCARP are unclear. In this study, we
      analyzed the function of FLVCR1 mutants by using a fluorescent heme analog as a
      transporter substrate, and found that all 4 FLVCR1 mutants lost their heme export
      activity. To investigate the mechanism responsible for this loss of activity, we
      determined the subcellular localization of FLVCR1 mutants. FLVCR1 mutants did not
      localize to the plasma membrane and were observed in intracellular structures,
      including lysosomes. We hypothesize that the loss of function of FLVCR1 mutants
      is caused by their mislocation. We examined the half-life of FLVCR1 in cells,
      which was >16h for wild-type FLVCR1 compared with 2-4h for the mutants. Based on
      these results, we propose that FLVCR1 mutants failed to fold properly in the ER,
      were rapidly degraded in the lysosomes, and therefore, could not export heme out
      of cells. Thus, accumulation of heme in FLVCR1-mutant cells could cause cellular
      toxicity.

PMID- 22483576
TI  - Type 2 diabetes mellitus patients manifest characteristic spatial EMG potential
      distribution pattern during sustained isometric contraction.
AB  - AIM: The purpose of the present study is to investigate spatial surface
      electromyography (SEMG) potential distribution pattern in type 2 diabetes
      mellitus (T2DM) patients. METHODS: Nine T2DM patients and nine age-matched
      healthy men (CON) performed a sustained isometric knee extension at 10% of
      maximal voluntary contraction for 120s. Multi-channel SEMG was recorded from the
      vastus lateralis muscle by means of 64 electrodes. To characterize spatial SEMG
      potential distribution pattern, modified entropy and correlation coefficients
      between same electrode locations were calculated at 15, 60 and 120s for the root
      mean square values. RESULTS: At 60 and 120s, modified entropy in T2DM was
      significantly lower than those in CON (p<0.05). Correlation coefficients for T2DM
      were significantly higher than those for CON at 60 and 120s (p<0.05). CONCLUSION:
      From these results, we suggested that T2DM patients continue to recruit limited
      and same motor units during the sustained contraction at low force level.

PMID- 22483578
TI  - Repeat percutaneous treatment of a large vein graft aneurysm with covered stents.
AB  - We present a case of repeat percutaneous intervention on a coronary artery bypass
      vein graft using polytetrafluoroethylene (PTFE) covered stents. The original
      intervention was performed using a combination of PTFE covered stents and bare
      metal stents for a large vein graft aneurysm. Successful exclusion of the
      aneurysm was demonstrated on follow up angiography. The patient represented six
      years after the original intervention with a non ST-segment elevation myocardial
      infarction. Further angiography demonstrated a recurrence of the aneurysm which
      we presumed to be due to late malapposition and required repeat PTFE covered
      stent deployment.

PMID- 22483577
TI  - Resource utilisation and clinical data before and after switching between short
      acting human insulin and rapid-acting insulin analogues in patients with type 2
      diabetes: the SWING study.
AB  - AIM: SWING was a prospective, observational study conducted in nine European
      countries primarily to assess direct treatment costs when switching from short
      acting human insulins to rapid-acting insulin analogues (H-A) or vice versa (A-H)
      in patients with type 2 diabetes. METHODS: Data were collected at a baseline
      visit (time of switch) and at approximately 3, 6 and 12 months post-switch.
      RESULTS: In total, 2389 patients switched from H-A (n=2203) or A-H (n=186);
      another 603 were enrolled but ineligible. Mean (SD) direct diabetes-related costs
      (pro-rated to account for variable visit schedules) were ?548.7 (865.8) 6 months
      prior to switch, ?625.6 (1474.9) at 0-6 months and ?568.6 (590.7) 6-12 months
      following switch for H-A, and ?544.5 (421.0), ?481.0 (301.5) and ?461.6 (335.0)
      for A-H, respectively. Mean (SD) HbA(1c) decreased over 12 months by 1.08 (1.53)%
      units H-A and 1.17 (1.45)% units A-H. A small decline in hypoglycaemia occurred
      over time, but there were no clinically meaningful changes in mean PROs.
      CONCLUSIONS: There were small changes in mean direct diabetes-related costs
      (following adjustment for time interval) in patients switching in either
      direction. Improvements in mean HbA(1c) and incidence of hypoglycaemia cannot
      necessarily be attributed to therapeutic switch.

PMID- 22483579
TI  - Endoscopic adrenalectomy in large adrenal tumors.
AB  - BACKGROUND: The purpose of this study was to evaluate the frequency of
      malignancy, oncologic outcome and perioperative morbidity between small (<=60 mm)
      and large (>60 mm) adrenal tumors treated by endoscopic adrenalectomy (EA).
      METHODS: EA was performed in 289 consecutive patients with a mean follow-up of
      87.7 +/- 45.1 months. Patients were divided in those with tumor size <=60 mm
      (group 1; n = 252) and >60 mm (group 2; n = 37). Data on patient's age, gender,
      hormone function, tumor side, operation time, postoperative complications,
      conversion to open approach, and rate of malignancy were analyzed. Furthermore,
      disease-free survival in malignant tumors was estimated and compared between both
      groups. RESULTS: Patient age (P = .43), gender (P = .09), tumor side (P = .17),
      and operative time (P = .33) showed no difference in both groups. Functioning
      tumors were observed in 85% of patients in group 1 compared with 46% in group 2
      (P = .0001). Seven (2.8%) patients in group 1 and 7 (18.9%) in group 2 had
      malignant tumors (P = .0001). Neither rate of conversion (P = .71) and
      postoperative complication (P = .27) nor recurrence of malignancy (P = .48)
      differed between both groups. Estimated disease-free survival after 5 years in
      malignant lesions was 87.5 +/- 11.7% for group 1 and 62.5 +/- 21.3% for group 2
      (P = .49). CONCLUSION: EA is a safe and feasible procedure in the majority of
      large adrenal tumors. Tumor size does not affect the outcome of surgery. In case
      of malignancy, it does not increase the rate of local recurrence. In experienced
      hands, tumor size should not influence the decision of surgical access
      (endoscopic versus open).

PMID- 22483580
TI  - Superior mesenteric artery syndrome.

PMID- 22483582
TI  - Discovery of small molecule HIV-1 integrase dimerization inhibitors.
AB  - Human immunodeficiency virus-1 integrase (HIV-1 IN) inserts the viral DNA into
      host cell chromatin in a multistep process. This enzyme exists in equilibrium
      between monomeric, dimeric, tetrameric and high order oligomeric states. However,
      monomers of IN are not capable of supporting its catalytic functions and the
      active form has been shown to be at least a dimer. As a consequence, the
      development of inhibitors targeting IN dimerization constitutes a promising novel
      antiviral strategy. In this work, we successfully combined different
      computational techniques in order to identify small molecule inhibitors of IN
      dimerization. Additionally, a novel AlphaScreen-based IN dimerization assay was
      used to evaluate the inhibitory activities of the selected compounds. To the best
      of our knowledge, this study represents the first successful virtual screening
      and evaluation of small molecule HIV-1 IN dimerization inhibitors, which may
      serve as attractive hit compounds for the development of novel anti-HIV.

PMID- 22483581
TI  - Using community-based participatory research (CBPR) to develop a community-level
      HIV prevention intervention for Latinas: a local response to a global challenge.
AB  - INTRODUCTION AND BACKGROUND: The arsenal of interventions to reduce the
      disproportionate rates of HIV and sexually transmitted disease (STD) infection
      among Latinos in the United States lags behind what is available for other
      populations. The purpose of this project was to develop an intervention that
      builds on existing community strengths to promote sexual health among immigrant
      Latinas. METHODS: Our community-based participatory research (CBPR) partnership
      engaged in a multistep intervention development process. The steps were to (1)
      increase Latina participation in the existing partnership, (2) establish an
      intervention team, (3) review the existing sexual health literature, (4) explore
      health-related needs and priorities of Latinas, (5) narrow priorities based on
      what is important and changeable, (6) blend health behavior theory with Latinas'
      lived experiences, (7) design an intervention conceptual model, (8) develop
      training modules and (9) resource materials, and (10) pretest and (11) revise the
      intervention. RESULTS: The MuJEReS intervention contains five modules to train
      Latinas to serve as lay health advisors (LHAs) known as "Comadres." These modules
      synthesize locally collected data with other local and national data, blend
      health behavior theory with the lived experiences of immigrant Latinas, and
      harness a powerful existing community asset, namely, the informal social support
      Latinas provide one another. CONCLUSION: This promising intervention is designed
      to meet the sexual health priorities of Latinas. It extends beyond HIV and STDs
      and frames disease prevention within a sexual health promotion framework. It
      builds on the strong, preexisting social networks of Latinas and the preexisting,
      culturally congruent roles of LHAs.

PMID- 22483583
TI  - Synthesis and antitumor-evaluation of 1,3,4-thiadiazole-containing
      benzisoselenazolone derivatives.
AB  - A series of novel 1,3,4-thiadiazole-containing benzisoselenazolone derivatives
      were prepared by the condensation of 2-chloroselenobenzoyl chloride and 2-amino-5
      substituted-1,3,4-thiadiazole. Their in vitro antiproliferative activities were
      evaluated in SSMC-7721, MCF-7 and A-549 cells. The results suggest that, in
      different tumor cells, some compounds have good antiproliferative activity,
      certain selectivity and potential value of further research.

PMID- 22483584
TI  - Development of rationally designed DNA N6 adenine methyltransferase inhibitors.
AB  - A series of bisubstrate inhibitors for DNA N6 adenine methyltransferase (Dam)
      have been synthesized by linking an amine analogue of S-adenosylmethionine to an
      aryl moiety designed to probe the binding pocket of the DNA adenine base. An
      initial structure-activity relationship study has identified substituents that
      increase inhibitor potency to the ~10 MUM range and improve selectivity against
      the human cytosine methyltransferase Dnmt1.

PMID- 22483585
TI  - Quinolinyl- and phenantridinyl-acetamides as bradykinin B1 receptor antagonists.
AB  - A new series of quinolinyl- and phenantridinyl-acetamides were synthesizer and
      evaluated against bradykinin B1 receptor. In vitro metabolic stability data were
      reported for the key compounds.The analgesic effect of compound 20 from the
      phenantridine series was proved in-vivo.

PMID- 22483586
TI  - Moracin M from Morus alba L. is a natural phosphodiesterase-4 inhibitor.
AB  - Phosphodiesterase-4 (PDE4) has been identified to be a promising target for
      treatment of asthma. Moracin M extracted from Chinese herbal drug 'Sang-Bai-Pi'
      (Morus alba L.) was studied for the inhibitory affinity towards PDE4. It
      inhibited PDE4D2, PDE4B2, PDE5A1, and PDE9A2 with the IC(50) values of 2.9, 4.5,
      >40, and >100 MUM, respectively. Our molecular docking and 8ns molecular dynamics
      (MD) simulations demonstrated that moracin M forms three hydrogen bonds with
      Gln369, Asn321, and Asp318 in the active site and stacks against Phe372. In
      addition, comparative kinetics analysis of its analog moracin C was carried out
      to qualitatively validate their inhibitory potency as predicted by the binding
      free energy calculations after MD simulations.

PMID- 22483587
TI  - Changing the game; some thoughts on future healthcare demands, technology,
      nursing and interprofessional education.
AB  - This editorial discusses the conclusions of a number of high-profile reports on
      the future of healthcare provision, and healthcare professional education. The
      need for the realignment of service provision, regulation, interdisciplinary
      healthcare and supporting education is discussed in the context of rapid
      technological and social change.

PMID- 22483588
TI  - Significance and association of serum uric acid (UA) levels with components of
      metabolic syndrome (MS) in the elderly.
AB  - Information concerning the association of serum UA levels and the development of
      MS in the Chinese aging population is limited. The aims of this study were to
      investigate age-related metabolic disorders and analyze the relationship between
      serum UA levels and the components of MS in the elderly. This cross-sectional
      observational study was performed in subjects from the Department of Health
      Examination, including 1182 subjects aged ?65 years; among these subjects, 528
      were women (mean age, 70.7 +/- 4.8 years) and 654 were men (mean age, 71.4 +/-
      5.3 years). All the subjects underwent three-dimensional (3-D) whole-body
      scanning for accurate anthropometric measurements. Data analyses were performed
      using SPSS software. RESULTS: MS, hyperuricemia, hypertension, and diabetes
      mellitus (DM) were present in 53.9%, 40.6%, 33.1%, and 30.1% of the subjects,
      respectively. Univariate statistical analysis showed that age, blood pressure,
      blood sugar levels, high-density lipoprotein levels, triglyceride levels, WBC
      count, and related anthropometric indices differed significantly in subjects
      categorized according to serum UA levels. In conclusion, our study showed that a
      high percentage of elderly subjects had hyperuricemia. The results showed an
      association between serum UA levels and cardiovascular risk factors, and this
      finding warrants concern with regard to the aging population.

PMID- 22483589
TI  - Age-related changes in the thickness of the deep and superficial abdominal
      muscles in women.
AB  - The study investigated age-related changes in the thickness of the deep and
      superficial abdominal muscles of 103 healthy women who could walk independently
      The participants were classified into five age groups: young (n=26; 20-24 years),
      young adult (n=26; 25-44 years), middle-aged (n=16; 45-64 years), young-old
      (n=16; 65-74 years), and old-old (n=19; 75-85 years). The muscle thicknesses of
      the right rectus abdominis, external oblique, internal oblique, and transversus
      abdominis were measured using ultrasound imaging. The rectus abdominis was
      significantly thicker in the young group compared with the young adult, middle
      aged, young-old, and old-old groups (p<0.05). The external oblique and internal
      oblique muscles were significantly thicker in the young group compared with the
      middle-aged, young-old, and old-old groups (p<0.05). However, there were no
      significant differences in the thickness of the transversus abdominis between
      groups. The results suggest that age-related muscle atrophy occurs from an early
      age in superficial abdominal muscles, such as rectus abdominis, and that age
      related atrophy is less in deep abdominal muscles such as the transversus
      abdominis.

PMID- 22483590
TI  - Radiofluorinated histamine H3 receptor antagonist as a potential probe for in
      vivo PET imaging: radiosynthesis and pharmacological evaluation.
AB  - The histamine H(3) receptor (H(3)R) plays a role in cognition and memory
      processes and is implicated in different neurological disorders, including
      Alzheimer's disease, schizophrenia, and narcolepsy. In vivo studies of the H(3)R
      occupancy using a radiolabeled PET tracer would be very useful for CNS drug
      discovery and development. We report here the radiosynthesis, in vitro and in
      vivo evaluation of a novel (18)F-labeled high-affinity H(3)R antagonist (18)F
      ST889. The radiosynthesis was accomplished via nucleophilic substitution of the
      mesylate leaving group with a radiochemical yield of 8-20%, radiochemical purity
      >99%, and specific radioactivity > 65 GBq/MUmol. (18)F-ST889 exhibited high in
      vivo stability and rather low lipophilicity (logD(7.4)=0.35 +/- 0.09). In vitro
      autoradiography showed specific binding in H(3)R-rich brain regions such as
      striatum and cortex. However, in vivo PET imaging of the rat brain with (18)F
      ST889 was not successful. Possible reasons are discussed.

PMID- 22483591
TI  - Identification of novel isocytosine derivatives as xanthine oxidase inhibitors
      from a set of virtual screening hits.
AB  - In recent years, xanthine oxidase has emerged as an important target not only for
      gout but also for cardiovascular and metabolic disorders involving hyperuricemia.
      Contrary to popular belief, recent clinical trials with uricosurics have
      demonstrated that enhanced excretion of uric acid is, by itself, not adequate to
      treat hyperuricemia; simultaneous inhibition of production of uric acid by
      inhibition of xanthine oxidase is also important. Virtual screening of in-house
      synthetic library followed by in vitro and in vivo testing led to the
      identification of a novel scaffold for xanthine oxidase inhibition. In vitro
      activity results corroborated the results from molecular docking studies of the
      virtual screening hits. The isocytosine scaffold maintains key hydrogen bonding
      and pi-stacking interactions in the deep end of the xanthine-binding pocket,
      which anchors it in an appropriate pose to inhibit binding of xanthine and shows
      promise for further lead optimization using structure-based drug design approach.

PMID- 22483592
TI  - Design, synthesis and biological activities of thiourea containing sorafenib
      analogs as antitumor agents.
AB  - A novel series of diaryl thiourea containing sorafenib derivatives 9a-t was
      designed and synthesized. The structures of all the newly synthesized compounds
      were determined by (1)H NMR, (13)C NMR and HRMS. Their antiproliferative
      activities against HCT116 and MDA-MB-231 cell lines, and their inhibitory
      activities against the phosphorylation of VEGFR were evaluated and described.
      Some of the compounds showed significant activities against both cell lines and
      VEGFR. Compounds 9g, 9m, 9o and 9p demonstrated competitive antiproliferative
      activities to sorafenib, the reference standard, while compounds 9d, 9m, and 9p
      showed significant inhibitory activities against the phosphorylation of VEGFR.

PMID- 22483593
TI  - Subacromial corticosteroid injection on poststroke hemiplegic shoulder pain: a
      randomized, triple-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the effect of subacromial corticosteroid injection on
      hemiplegic shoulder pain (HSP). DESIGN: Multicenter, randomized, triple-blind,
      placebo-controlled trial. SETTING: Three primary and 1 university-affiliated
      tertiary-care hospitals. PARTICIPANTS: Poststroke HSP patients (N=58) with
      evidence of rotator cuff disorder. INTERVENTIONS: Participants were randomly
      assigned to receive ultrasound-guided subacromial injection with triamcinolone
      40mg (treatment group, n=29), or lidocaine (placebo group, n=29). After a single
      injection, participants were followed up for 8 weeks. MAIN OUTCOME MEASURES:
      Visual analog scale (VAS) of the average shoulder pain level at day and night
      (VAS-day/night, the primary outcome measures), Modified Barthel Index, Shoulder
      Disability Questionnaire (SDQ), and angles of shoulder active range of motion
      (flexion, abduction, external rotation, and internal rotation) at pretreatment
      and weeks 2, 4, and 8 posttreatment. RESULTS: There was no significant difference
      between the 2 groups in the main outcome measures at pretreatment. Compared with
      the placebo group, VAS-day/night, SDQ, flexion, external rotation, and internal
      rotation showed significant improvement in the treatment group. CONCLUSIONS: To
      our knowledge, this is the first randomized, placebo-controlled study to assess
      the efficacy of subacromial injection in HSP patients with evidence of rotator
      cuff disorder. Subacromial corticosteroid injection showed improvement in pain,
      disability, and active range of motion, and the duration of its efficacy
      continued up to 8 weeks.

PMID- 22483594
TI  - Imidazolium salt attenuates thioacetamide-induced liver fibrosis in mice by
      modulating inflammation and oxidative stress.
AB  - BACKGROUND AND AIM: Oxidative stress contributes to liver fibrosis through the
      activation of hepatic stellate cells. In a cell-based screening study, a class of
      imidazolium salts demonstrates anti-fibrogenic properties. Little is known on
      imidazolium salt mechanistic effects. We investigated the anti-fibrogenic effect
      of one of the imidazolium salts, 1,3-bisbenzylimidazoliumbromide (DBZIM), in a
      chronic mouse model of liver fibrosis and evaluated the mechanism of this
      treatment. METHODS: Liver fibrosis was induced in mice by oral feeding of
      thioacetamide for 16 weeks. DBZIM was administered weekly, starting on the first
      day or 12 weeks from the day of thioacetamide administration. Hepatic function,
      histology and oxidative stress were examined. Expression of key inflammatory
      molecules and the molecular mechanism of DBZIM were assessed in hepatic stellate
      cells. RESULTS: DBZIM decreased the fibrogenic response in thioacetamide-mice as
      measured by collagen deposition and alpha-smooth muscle actin expression
      (P<0.01). DBZIM improved liver function and reduced both oxidative damage and
      inflammation (P<0.01). Most importantly, our findings report the discovery that
      astrocyte elevated gene-1, involved in tumour progression, was up-regulated in
      thioacetamide-mice and DBZIM modulated astrocyte elevated gene-1 and NF-kappaB
      expression. CONCLUSION: These findings indicate DBZIM is a potent therapeutic
      agent for the treatment of liver fibrosis.

PMID- 22483595
TI  - Pseudometallophytes colonising Pb/Zn mine tailings: a description of the plant
      microorganism-rhizosphere soil system and isolation of metal-tolerant bacteria.
AB  - The plant-microorganism-soil system of three pseudometallophytes (Betula
      celtiberica, Cytisus scoparius and Festuca rubra) growing in a Pb/Zn mine was
      characterised. Plant metal accumulation, soil metal fractions (rhizosphere and
      non-vegetated) and bacterial densities were determined. Total Cd, Pb and Zn in
      non-vegetated soils was up to 50, 3000 and 20,000 mg kg(-1) dry weight,
      respectively. The residual fraction dominated non-vegetated soils, whereas plant
      available fractions became important in rhizosphere soils. All plant species
      effectively excluded metals from the shoot. F. rubra presented a shoot:root
      transport factor of <=0.2 and this population could be useful in future
      phytostabilisation trials. Culturable bacterial densities and diversity were low
      (predominantly Actinobacteria). Rhizosphere soils hosted higher total and metal
      tolerant bacterial densities. Seventy-four metal-tolerant rhizobacteria were
      isolated, and characterised genotypically (BOX-PCR, 16S rDNA) and phenotypically
      [Cd/Zn tolerance, biosurfactant production and plant growth promoting (PGP)
      traits]. Several isolates resisted high concentrations of Cd and Zn, and only a
      few presented PGP traits. Fourteen isolates were evaluated for promoting plant
      growth of two species (Salix viminalis and Festuca pratensis). Thirteen
      inoculants enhanced growth of F. pratensis, while only three enhanced growth of
      S. viminalis. Growth enhancement could not always be related to isolate PGP
      traits. In conclusion, some isolates show potential application in
      phytostabilisation or phytoextraction techniques.

PMID- 22483596
TI  - Improved lead recovery and sulphate removal from used lead acid battery through
      electrokinetic technique.
AB  - This paper presents improvement in lead (Pb) recovery and sulphate removal from
      used Pb acid battery (ULAB) through Electrokinetic technique, a process aimed to
      eliminate environmental pollution that arises due to emission of gases and metal
      particles from the existing high temperature pyrometallurgical process. Two
      different cell configurations, (1) one with Nafion membrane placed between anode
      and middle compartments and Agar membrane between cathode and middle compartments
      and (2) another with only Agar membrane placed between both sides of the middle
      compartments were designed for the Pb and sulphate separation from ULAB. This
      paper concludes that the cell with only Agar membranes performed better than the
      cell with Nafion and Agar membranes in combinations and also explains the
      mechanism underlying the chemical and electrochemical processes in the cell.

PMID- 22483597
TI  - Effects of Mn(II) on the sorption and mobilization of As(V) in the presence of
      hematite.
AB  - In this study, the effects of Mn(II) on the sorption and mobilization of As(V) by
      synthetic hematite were investigated. Our results showed that As(V) removal by
      hematite was evidently dependent on pH, and simultaneous addition of Mn(II) and
      As(V) into hematite suspension resulted in more removal of As(V) via
      electrostatic attraction at pH 4.0, 7.0 and 8.3. However, in Mn(II) pre-loaded
      system, the removal percentages of As(V) at pH 8.3 decreased by 17.0%, 20.7% and
      26.7% after 24h at the aging time of 2, 12 and 36 h, respectively. The
      concentrations of the released As(V) after the addition of 1mM Mn(II) were 23.6,
      12.9 and 7.0 MUM at pH 8.5 in 2, 3 and 4 g L(-1) hematite suspension,
      respectively. But Ca(2+) did not show such an effect under similar experimental
      conditions. Abiotic oxidation of Mn(II) on hematite played an important role in
      As(V) mobilization. The growing thin layer of Mn(III, IV) (hydr)oxides (MnO(x))
      formed on hematite would take up the sorption sites pre-occupied by As(V) and
      resulted in the release of the adsorbed As(V) back into solution. This study
      enriched our understanding on As(V) fate in the coexistence of iron oxides and
      Mn(II).

PMID- 22483598
TI  - Reduction of nitrobenzene by steel convert slag with Fe(II) system: the role of
      calcium in steel slag.
AB  - Experiments were conducted to examine of nitrobenzene reduction by steel convert
      slag (SCS) with Fe(II) system. The results showed SCS with Fe(II) was an
      effective reductant for nitrobenzene at pH 5.5-6.5. Further analysis suggested
      Fe(II) was adsorbed by SCS through ion replacement with SCS-bound Ca(II). More
      than 81% of the total Ca(II) in SCS was replaced with dissolved Fe(II),
      indicating a high adsorption capacity for Fe(II) (more than 5.82 mmol Fe(II)/g
      SCS). A three step mechanism (replacement process, conversion process and
      electron transfer process) was proposed for nitrobenzene reduction by SCS with
      Fe(II) system. The amount of Ca(II) in SCS determined the adsorption capacity for
      Fe(II) and further determined the reduction capacity of SCS with Fe(II) system.

PMID- 22483599
TI  - Bioavailability assessment of hexachlorobenzene in soil as affected by wheat
      straw biochar.
AB  - Biochar incorporation with soil could increase sorption of organic contaminants,
      thereby reducing their bioavailability. In this study, the effects of wheat straw
      biochar on the sorption, dissipation and bioavailability of hexachlorobenzene
      (HCB), a typical persistent organic pollutant (POP), were investigated in
      laboratory experiments. We observed that HCB sorption by biochar was 42 times
      higher than that by soil and the sorption isotherm was linear for the
      concentration range studied. Biochar amendments reduced HCB dissipation,
      volatilization and earthworm (Eisenia foetida) uptake of HCB from soil.
      Hydroxypropyl-beta-cyclodextrin extraction correlated better with the earthworm
      bioassay than butanol extraction of HCB in biochar-amended soil. The results of
      both chemical extraction and earthworm bioassay indicate that biochar amendment
      of soil resulted in a rapid reduction in the bioavailability of HCB, even for the
      0.1% biochar application rate. This suggested that wheat straw biochar could
      potentially be used in immobilizing POPs in contaminated sites.

PMID- 22483600
TI  - US-guided core needle biopsy: false-negatives. How to reduce them?

PMID- 22483601
TI  - An experimental study on acute brain radiation injury: dynamic changes in proton
      magnetic resonance spectroscopy and the correlation with histopathology.
AB  - PURPOSE: To investigate the correlation between the alterations of single-voxel
      (1)H MRS and the histopathological characteristics of radiation brain injury
      following radiation. MATERIALS AND METHODS: Twenty-seven rabbits were randomized
      into nine groups to receive radiation with a single dose of 25 Gy. The
      observation time points included a pre-radiation and 1, 2, 3, 4, 5, 6, 7, and 8
      wk following radiation. Each treatment group underwent conventional MRI and
      single-voxel 1H MRS, N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr)
      were observed over the region of interest, and the presence or absence of lactate
      (Lac) and lipid (Lip) was detected. Histological specimens of each group were
      obtained after image acquisition. RESULTS: The values of Cho were significantly
      increased in the first 3 wk, and decreased over the following 5 wk after
      radiation. Levels of NAA showed a trend toward a decrease 5 wk after radiation.
      The levels of Cr were not changed between before and after radiation. The Cho/NAA
      metabolic ratio was significantly increased in weeks 6, 7, and 8 following
      irradiation, compared to pre-radiation values. Vascular and glial injury appeared
      on 2 wk after RT in the histology samples, until 4 wk after RT, necrosis of the
      oligodendrocytes, neuronal degeneration and demyelination could be observed.
      CONCLUSIONS: MRS is sensitive to detect metabolic changes following radiation,
      and can be used in the early diagnosis of radiation brain injury.

PMID- 22483602
TI  - Migration of a port-a-cath from the femoral vein into the duodenum 10 months
      after implantation.

PMID- 22483603
TI  - Targeting PI3K isoforms and SHIP in the immune system: new therapeutics for
      inflammation and leukemia.
AB  - PI3K is critical for the normal function of the immune system, however
      dysregulated PI3K mediated signaling has been linked to the development of many
      immune mediated pathologies. This review describes current progress in the
      development of isoform-specific PI3K inhibitors that hold promise for the
      treatment of hematopoietic malignancies as well as for inflammatory and
      autoimmune diseases. A SH2-domain containing inositol-5-phosphatase (SHIP) is a
      regulator of PI3K signaling, and is also discussed as a potential drug target for
      immunomodulation and the treatment of leukemia. Recent progress has been made in
      the development of small molecule compounds that potently and selectively
      modulate SHIP activity and hence provide a novel mechanism to alter PI3K mediated
      signaling.

PMID- 22483604
TI  - The sarcomeric cytoskeleton as a target for pharmacological intervention.
AB  - Many diseases of heart and skeletal muscle, from heart failure to muscle atrophy,
      pose unmet needs for specific and effective treatments. Recent advances suggest
      that sarcomeres, the smallest contractile units of heart and skeletal muscles,
      can be viable pharmacological targets. In sarcomeres, the contractile actin and
      myosin filaments are organised by a network of proteins combining structural and
      signalling functions, forming the sarcomeric cytoskeleton. This includes the
      giant proteins titin, obscurin and nebulin, which contain protein-binding sites
      along with signalling domains such as protein kinase, Rho activator, and Src
      homology domains. These signalling domains have recently been implicated in
      sarcomere assembly, and the regulation of muscle contractile and metabolic
      adaptation. Although many functions of sarcomeric proteins remain to be
      discovered, their potential as pharmacological targets is now emerging. Here, we
      will review recent insight into the physiological and pathological signalling
      functions of sarcomeric cytoskeletal proteins and discuss new aspects and
      strategies in skeletal muscle signalling, pathomechanisms and therapy.

PMID- 22483605
TI  - The influence of body weight, body mass index and gender on plantar pressures:
      results of a cross-sectional study of healthy children's feet.
AB  - The purpose of this study was to determine if plantar pressure data in 4-7 year
      old children with normal development: (1) required normalising by body mass
      and/or body mass index and (2) should be separated or pooled for boys and girls.
      The outcome will guide the management of plantar pressure data in future work
      investigating changes in plantar pressure distribution with increasing age. In a
      cross-sectional design, 98 British children (45 girls) with no orthopaedic,
      neurological or developmental disorders provided plantar pressure measurements
      during walking. Peak plantar pressure and plantar pressure time integrals were
      obtained from nine areas under the foot: calcaneus, medial and lateral midfoot,
      each of the five metatarsals and the hallux. Body weight and body mass index
      demonstrated low and weak degrees of association (r<=0.48, p<0.05) with plantar
      pressure data. Boys and girls showed no difference in plantar pressures (p<0.05).
      Plantar pressure data for 4-7 year olds does not require normalisation with body
      mass or body mass index, and can be pooled for boys and girls.

PMID- 22483606
TI  - Impact of axillary ultrasound and core needle biopsy on the utility of
      intraoperative frozen section analysis and treatment decision making in women
      with invasive breast cancer.
AB  - BACKGROUND: Our objective was to evaluate the impact of preoperative axillary
      ultrasound and core needle biopsy (CNB) on breast cancer treatment decision
      making. A secondary aim was to evaluate the impact on the utility of
      intraoperative sentinel lymph node (SLN) frozen section. METHODS: A review of 84
      patients with clinically negative axilla who underwent axillary ultrasound was
      performed. Sensitivity, specificity, and positive/negative predictive value for
      axillary ultrasound with CNB was calculated. RESULTS: Thirty-one (37%) had
      suspicious nodes. Of 27 amenable to CNB, 12 (14%) were malignant, changing
      treatment plans. The sensitivity of ultrasound and CNB was 54% and specificity
      100%; the positive and negative predictive values were 100% and 80%,
      respectively. In 41 patients with normal ultrasounds who underwent SLN frozen
      section, 10 (24%) were positive. CONCLUSIONS: Preoperative axillary ultrasound
      impacts treatment decision making in 14%. With a sensitivity of 54%, it is a
      useful adjunct to, but not replacement for, SLN biopsy. Frozen section remains of
      utility even after a negative axillary ultrasound.

PMID- 22483607
TI  - Variability and errors when applying the BIRADS mammography classification.
AB  - To standardize mammographic reporting, the American College of Radiology
      mammography developed the Breast Imaging Reporting and Data System (BIRADS)
      lexicon. However, wide variability is observed in practice in the application of
      the BIRADS terminology and this leads to classification errors. This review
      analyses the reasons for variations in BIRADS mammography, describes the types of
      errors made by readers with illustrated examples, and details BIRADS category 3
      which is the most difficult category to use in practice.

PMID- 22483608
TI  - Synthesis and evaluation of 2-[2-(phenylthiomethyl)-1H-benzo[d] imidazol-1
      yl)acetohydrazide derivatives as antitumor agents.
AB  - A novel class of acetylhydrazone derivatives (5a-x) containing 2
      (phenylthiomethyl)-1H-benzo-[d]-imidazole moieties are synthesizer, and their
      antitumor activities against A549, HCT116, HepG2, PC-9, and A375 were determined
      by the MTT assay. Among them are N-(2,4-dihydroxybenzylidene)-2-(2
      (phenylthiomethyl)-1H-benzo[d]-imidazol-1-yl)acetohydrazide (5a) and N-(5-bromo-2
      hydroxy-benzylidene)-2-(2-(phenylthiomethyl)-1H-benzo[d]-imidazol-1
      yl)acetohydrazide (5d) which displayed excellent cancer inhibitory activity
      against the tested cancer cells (IC(50) 4-17 MUM), compared with 5-FU and
      SU11248. The others have moderate to weak inhibitory activity against the tested
      cancer cell lines.

PMID- 22483609
TI  - Lead optimization of 4,4-biaryl piperidine amides as gamma-secretase inhibitors.
AB  - Alzheimer's disease is a major unmet medical need with pathology characterized by
      extracellular proteinaceous plaques comprised primarily of beta-amyloid. gamma
      Secretase is a critical enzyme in the cellular pathway responsible for the
      formation of a range of beta-amyloid peptides; one of which, Abeta42, is believed
      to be responsible for the neuropathological features of the disease. Herein, we
      report 4,4 disubstituted piperidine gamma-secretase inhibitors that were
      optimized for in vitro cellular potency and pharmacokinetic properties in vivo.
      Key agents were further characterized for their ability to lower cerebral Abeta42
      production in an APP-YAC mouse model. This structural series generally suffered
      from sub-optimal pharmacokinetics but hypothesis driven lead optimization enabled
      the discovery of gamma-secretase inhibitors capable of lowering cerebral Abeta42
      production in mice.

PMID- 22483610
TI  - Efficient synthesis of Guanfu base G via highly regioselective lipase-catalyzed
      acylation in non-aqueous phase.
AB  - Lipase-catalyzed acylation of Guanfu alcohol-amine (GFAA) with vinyl acetate (VA)
      was performed in non-aqueous system for the preparation of Guanfu base G (GFG), a
      plant-originated alkaloid with significant antiarrhythmic activity. Among the
      eight lipases from different origins, Novozym 435 was found to be the best
      biocatalyst. The most suitable molecular sieve amount, substrate concentration,
      molar ratio of VA to GFAA, enzyme amount and reaction temperature were proved to
      be 40 mg/mL, 6 MUmol/mL, 10:1, 2mg/mL and 50  degrees C, respectively. A maximum
      GFG yield of 37.4% was achieved under the selected conditions with methanol
      served as the optimal reaction medium. The structure of the acetylated product
      was elucidated by (1)H NMR and (13)C NMR analysis.

PMID- 22483611
TI  - Vertebral artery strains during high-speed, low amplitude cervical spinal
      manipulation.
AB  - Spinal manipulative therapy (SMT) has been recognized as an effective treatment
      modality for many back, neck and musculoskeletal problems. One of the major
      issues of the use of SMT is its safety, especially with regards to neck
      manipulation and the risk of stroke. The vast majority of these accidents involve
      the vertebro-basilar system, specifically the vertebral artery (VA) between
      C2/C1. However, the mechanics of this region of the VA during SMT are unexplored.
      Here, we present first ever data on the mechanics of this region during cervical
      SMT performed by clinicians. VA strains obtained during SMT are significantly
      smaller than those obtained during diagnostic and range of motion testing, and
      are much smaller than failure strains. We conclude from this work that cervical
      SMT performed by trained clinicians does not appear to place undue strain on VA,
      and thus does not seem to be a factor in vertebro-basilar injuries.

PMID- 22483612
TI  - The role of spinal manipulation in addressing disordered sensorimotor integration
      and altered motor control.
AB  - This review provides an overview of some of the growing body of research on the
      effects of spinal manipulation on sensory processing, motor output, functional
      performance and sensorimotor integration. It describes a body of work using
      somatosensory evoked potentials (SEPs), transcranial magnetic nerve stimulation,
      and electromyographic techniques to demonstrate neurophysiological changes
      following spinal manipulation. This work contributes to the understanding of how
      an initial episode(s) of back or neck pain may lead to ongoing changes in input
      from the spine which over time lead to altered sensorimotor integration of input
      from the spine and limbs.

PMID- 22483613
TI  - A descriptive study of research published in scientific nursing journals from
      1985 to 2010.
AB  - BACKGROUND: Numerous analyses of research published in scientific nursing
      journals have been examined over the past decades. However, a comprehensive
      analysis of trends in research has not been reported since 1980. OBJECTIVES: The
      aim of this analysis was to review randomly selected research articles published
      in four scientific nursing journals for the years 1985, 1990, 1995, 2000, 2005,
      and 2010 to identify changes in selected aspects of research and to compare the
      findings with those from an earlier similar study. DESIGN: This descriptive study
      used percentages to present trends in published studies in four scientific
      nursing journals for twenty-five years. METHODS: A total of 976 studies were
      identified; 50% were randomly selected for each year analyzed. The foci of the
      research problem, care orientation, conceptual bases, research designs, data
      analysis procedures, discussion of findings, and recommendations and implications
      were analyzed. RESULTS: Most studies from 1985 (66%) through 2010 (73%) focused
      on nursing practice issues; in 2010 they focused on primary health (46%) and
      chronicity (41%). A decrease in theory-testing research from 1985 (32%) to 2010
      (21%), and in theory-based studies from 1985 (31%) to 2010 (22%) was noted.
      Qualitative studies increased from 1985 (3%) to 2010 (21%). Psychological
      variables and adult populations continue to be studied mainly over 25 years. For
      quantitative studies, there were increases in correlational designs from 1985
      (35%) to 2010 (38%), experimental designs from 1985 (16%) to 2010 (18%), and
      methodological studies from 1985 (5%) to 2010 (24%). There were decreases in
      descriptive studies from 1985 (20%) to 2010 (5%), and comparative studies from
      1985 (19%) to 2010 (10%). The use of multivariate statistics increased over time.
      In 1985, 61% of researchers did not link their findings to theory guiding the
      study; 52% did not in 2010. For qualitative research, approximately 50% fell in
      the "other category" over the 25 years; in 2010, grounded theory (15%),
      phenomenological (15%) and ethnographic (20%) designs were used. CONCLUSIONS:
      Trends indicated that the building of science has been slow, incremental, and
      subtle, as found in the earlier study. Trends suggest a growing maturity in the
      research designs.

PMID- 22483614
TI  - Exploration of esophageal hiatus: does crural repair reduce proximal pouch
      distension?
AB  - BACKGROUND: Repair of a hiatal hernia during laparoscopic adjustable gastric
      banding is advisable; however, the practice of more active esophageal hiatus
      exploration and repair has been promoted with an expectation of reducing proximal
      gastric pouch distension (PPD). Our objective was to explore the relationship
      between crural exploration and repair (CR) and PPD in a private practice in
      Canada. METHODS: The data from 3000 consecutive patients who underwent primary
      laparoscopic adjustable banding procedures at a single center from February 2005
      to May 2011 were examined. Several analyses were performed, with the PPD cases
      carefully matched to historic (time-of-placement) and historic-, age-, and gender
      matched controls. RESULTS: Throughout the series, the PPD rates decreased and the
      CR rates increased. Revision for PPD was performed in 132 patients (4.4%). The
      patients with PPD were more likely to have undergone CR during primary surgery
      (odds ratio 1.5, 95% confidence interval 1.2-2.2, P = .001) compared with
      historic, and historic-, age-, and gender-matched controls (odds ratio 2.3, 95%
      confidence interval 1.4-3.8, P < .001). The findings were confirmed using
      adjusted binary logistic regression analysis controlling for age, gender, body
      mass index, and time-of-placement. This increased risk was most evident early in
      the series when incident PPD cases were greater. However, at no stage did CR
      reduce the risk of symmetric or asymmetric PPD. CONCLUSION: The results of the
      present analysis do not support the theory that increased exploration and repair
      of the esophageal hiatus reduces the incidence of PPD. There might be a role for
      CR at surgery for specific clinical indications. CR increases the complexity and
      possibly the risk of the procedure.

PMID- 22483615
TI  - Galactosemia: when is it a newborn screening emergency?
AB  - Classic galactosemia is an autosomal recessive disorder of carbohydrate
      metabolism, due to a severe deficiency of the enzyme, galactose-1-phosphate
      uridyltransferase (GALT), that catalyzes the conversion of galactose-1-phosphate
      and uridine diphosphate glucose (UDPglucose) to uridine diphosphate galactose
      (UDPgalactose) and glucose-1-phosphate. Upon consumption of lactose in the
      neonatal period, the affected infants develop a potentially lethal disease
      process with multiorgan involvement. Since the advent of newborn screening (NBS)
      for galactosemia, we rarely encounter such overwhelmingly ill newborns. After
      ascertainment that the positive NBS indicates the possibility of galactosemia due
      to GALT deficiency, the critical question for the physician is whether the infant
      has the classic or a variant form of GALT deficiency, as classic galactosemia is
      a medical emergency. However, there are over 230 GALT gene mutations that have
      been detected around the world. Yet, most positive NBS tests are due to the
      Duarte biochemical variant condition or a simple false positive. In order to make
      the correct decision as well as provide informative counseling to parents of
      infants with a positive NBS, I utilize a relatively simple classification scheme
      for GALT deficiency. There are three basic forms of GALT deficiency: 1) classic
      galactosemia; 2) clinical variant galactosemia; and 3) biochemical variant
      galactosemia. The classic genotype is typified by Q188R/Q188R, the clinical
      variant by S135L/S135L and the biochemical variant by N314D/Q188R. In classic
      galactosemia, the erythrocyte GALT enzyme activity is absent or markedly reduced,
      the blood galactose and erythrocyte galactose-1-phosphate levels are markedly
      elevated, and the patient is at risk to develop potentially lethal E. coli
      sepsis, as well as the long-term diet-independent complications of galactosemia.
      Patients with the clinical variant form require treatment but do not die from E.
      coli sepsis in the neonatal period. If the clinician suspects galactosemia, even
      if based on clinical findings alone, then the infant should be immediately placed
      on a lactose-restricted diet. The purpose of this review is to help the clinician
      make the correct therapeutic decision after an NBS test has returned positive for
      galactosemia.

PMID- 22483616
TI  - Nucleolin level in plant root meristematic cells under chilling stress and
      recovery.
AB  - Nucleolin and its homologues are multifunctional proteins which reside mainly in
      nucleoli of yeast, animal and plant cells. Hence, they are generally implicated
      in many stages of ribosome biosynthesis. In this study nucleolin was identified
      in root meristematic cell nucleoli of soybean plants subjected to chilling
      stress, recovered after chilling and under control conditions with the use of the
      immunogold electron microscopy technique. Soybean nucleoli exhibited various
      metabolic activities under these conditions (Stepinski, 2004). Current studies
      showed that the level of nucleolin, expressed as a number of gold grains per
      MUm(2), varied in particular subnucleolar regions in the soybean root
      meristematic cell nucleoli. Labeling density changed in these regions when plants
      were subjected to the given treatment. Most abundantly this protein was present
      in dense fibrillar component (DFC) around fibrillar centers (FCs) in the nucleoli
      of recovered plants, while in the nucleoli of stressed plants this region
      contained the lowest level of nucleolin. It can be supposed that nucleolin
      participates in ribosome biogenesis and its level is correlated with metabolic
      activity of soybean nucleoli - the more active nucleoli, the higher level of
      nucleolin and vice versa.

PMID- 22483617
TI  - The ubiquitin ligase Siah1 controls ELL2 stability and formation of super
      elongation complexes to modulate gene transcription.
AB  - Super elongation complexes (SECs) contain two different transcription elongation
      factors, P-TEFb and ELL1/2, linked by the scaffolding protein AFF4 or AFF1. They
      stimulate the expression of both normal and disease-related genes, especially
      those of HIV or those involved in leukemogenesis. Among all SEC subunits, ELL2 is
      stoichiometrically limiting and uniquely regulated at the level of protein
      stability. Here we identify the RING domain protein Siah1, but not the homologous
      Siah2, as the E3 ubiquitin ligase for ELL2 polyubiquitination and proteasomal
      degradation. Siah1 cannot access and ubiquitinate ELL2 bound to AFF4, although,
      at high concentrations, it also degrades AFF4/1 to destroy SECs. Prostratin and
      HMBA, two well-studied activators of HIV transcription and latency, enhance ELL2
      accumulation and SECs formation largely through decreasing Siah1 expression and
      ELL2 polyubiquitination. Given its importance in formation of SECs, the Siah1
      ubiquitination pathway provides a fresh avenue for developing strategies to
      control disease-related transcription.

PMID- 22483618
TI  - Lysyl oxidase-like 2 deaminates lysine 4 in histone H3.
AB  - Methylation of lysine 4 (K4) within histone H3 has been linked to active
      transcription and is removed by LSD1 and the JmjC domain-containing proteins by
      amino-oxidation or hydroxylation, respectively. Here, we describe the deamination
      catalyzed by Lysyl oxidase-like 2 protein (LOXL2) as an unconventional chemical
      mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry
      analyses demonstrated that recombinant LOXL2 specifically deaminates
      trimethylated H3K4. Moreover, LOXL2 activity is linked with the transcriptional
      control of CDH1 gene by regulating H3K4me3 deamination. These results reveal
      another H3 modification and provide a different mechanism for H3K4 modification.

PMID- 22483620
TI  - Structural and functional organization of the Ska complex, a key component of the
      kinetochore-microtubule interface.
AB  - The Ska complex is an essential mitotic component required for accurate cell
      division in human cells. It is composed of three subunits that function together
      to establish stable kinetochore-microtubule interactions in concert with the
      Ndc80 network. We show that the structure of the Ska core complex is a W-shaped
      dimer of coiled coils, formed by intertwined interactions between Ska1, Ska2, and
      Ska3. The C-terminal domains of Ska1 and Ska3 protrude at each end of the
      homodimer, bind microtubules in vitro when connected to the central core, and are
      essential in vivo. Mutations disrupting the central coiled coil or the
      dimerization interface result in chromosome congression failure followed by cell
      death. The Ska complex is thus endowed with bipartite and cooperative tubulin
      binding properties at the ends of a 350 A-long molecule. We discuss how this
      symmetric architecture might complement and stabilize the Ndc80-microtubule
      attachments with analogies to the yeast Dam1/DASH complex.

PMID- 22483619
TI  - mRNA decapping factors and the exonuclease Xrn2 function in widespread premature
      termination of RNA polymerase II transcription.
AB  - We report a function of human mRNA decapping factors in control of transcription
      by RNA polymerase II. Decapping proteins Edc3, Dcp1a, and Dcp2 and the
      termination factor TTF2 coimmunoprecipitate with Xrn2, the nuclear 5'-3'
      exonuclease "torpedo" that facilitates transcription termination at the 3' ends
      of genes. Dcp1a, Xrn2, and TTF2 localize near transcription start sites (TSSs) by
      ChIP-seq. At genes with 5' peaks of paused pol II, knockdown of decapping or
      termination factors Xrn2 and TTF2 shifted polymerase away from the TSS toward
      upstream and downstream distal positions. This redistribution of pol II is
      similar in magnitude to that caused by depletion of the elongation factor Spt5.
      We propose that coupled decapping of nascent transcripts and premature
      termination by the "torpedo" mechanism is a widespread mechanism that limits
      bidirectional pol II elongation. Regulated cotranscriptional decapping near
      promoter-proximal pause sites followed by premature termination could control
      productive pol II elongation.

PMID- 22483622
TI  - Compression of left main coronary artery by a dilated pulmonary artery in a
      female patient with atrial septal defect.

PMID- 22483623
TI  - Tako-Tsubo cardiomyopathy in a teen girl with pheochromocytoma.

PMID- 22483621
TI  - Localized dimerization and nucleoid binding drive gradient formation by the
      bacterial cell division inhibitor MipZ.
AB  - Protein gradients play a central role in the spatial organization of cells, but
      the mechanisms of their formation are incompletely understood. This study
      analyzes the determinants responsible for establishing bipolar gradients of the
      ATPase MipZ, a key regulator of division site placement in Caulobacter
      crescentus. We have solved the crystal structure of MipZ in different nucleotide
      states, dissected its ATPase cycle, and investigated its interaction with FtsZ,
      ParB, and the nucleoid. Our results suggest that the polar ParB complexes locally
      stimulate the formation of ATP-bound MipZ dimers, which are then retained near
      the cell poles through association with chromosomal DNA. Due to their intrinsic
      ATPase activity, dimers eventually dissociate into freely diffusible monomers
      that undergo spontaneous nucleotide exchange and are recaptured by ParB. These
      findings clarify the molecular function of a conserved gradient-forming system
      and reveal mechanistic principles that might be commonly used to sustain protein
      gradients within cells.

PMID- 22483624
TI  - Diagnosis of cardiac tumors: contribution of non-invasive cardiac imaging in
      routine practice.

PMID- 22483625
TI  - Early repolarization pattern predicts cardiac death and fatal arrhythmia in
      patients with vasospastic angina.
AB  - BACKGROUND: Early repolarization (ER), which is characterized by an elevation of
      J-point, is sometimes associated with fatal arrhythmia and sudden cardiac death
      in patients without structural heart disease. This study investigated the
      prevalence and prognostic significance of ER in patients with vasospastic angina
      (VA). METHODS: We assessed the ER pattern in 281 VA patients (mean age, 50.5 +/-
      7.9 years), and the prognostic modulation of ER-associated risk by ST-segment
      variations. RESULTS: Any type of ER >= 0.1 mV in inferior and/or lateral leads
      was persistently observed after chest pain in 60 (21.4%) VA patients. During the
      follow up period of 7.6 +/- 4.7 years, patients with ER had higher incidence of
      cardiac events including cardiac death, aborted sudden cardiac death or fatal
      arrhythmia than those with no ER (20.0% vs. 5.4%, p=0.001). Patients with ER >=
      0.1 mV and horizontal/descending ST variant (n=18) had an increased age- and sex
      adjusted hazard ratio of cardiac events (relative risk 8.12; 95% confidence
      interval 3.45-19.12). When modeled for ER in inferior leads and
      horizontal/descending ST-segment variant, the hazard ratio of cardiac events
      increased to 8.89 (95% confidence interval 3.78-20.91). However, in subjects with
      ascending ST variant, the relative risk for arrhythmic death was not
      significantly increased. CONCLUSION: ER was observed in a fifth of VA patients,
      and was associated with an increased risk of cardiac events in VA. However, it is
      also possible that, in patients with ER, VA might cause an adverse event or
      facilitate the diagnosis of ER.

PMID- 22483626
TI  - Mutational spectrum of the GATA5 gene associated with familial atrial
      fibrillation.

PMID- 22483627
TI  - Preoperative autologous blood donation and acute normovolemic hemodilution affect
      intraoperative blood loss during sagittal split ramus osteotomy.
AB  - INTRODUCTION: This study aimed to determine the effects of acute normovolemic
      hemodilution (ANH) using low-molecular-weight hydroxyethyl starch (LMW-HES) on
      intraoperative blood loss in patients who had received preoperative autologous
      blood donation (PABD) and had undergone sagittal split ramus osteotomy (SSRO).
      METHODS: Patients who had undergone SSRO were analyzed. All 250 patients received
      PABD of 400-800 mL until 2 weeks before surgery. ANH was performed by withdrawing
      whole blood, which was replaced by the same volume of LMW-HES. ANH was performed
      in 197 cases for 200 mL replacement (ANH-200) and in 5 cases for 400 mL
      replacement (ANH-400); it was not performed in 48 cases (ANH-0). RESULTS: Blood
      loss in ANH-200 was greater than that in ANH-0, despite no differences in
      hemoglobin concentrations at pre- and post-PABD, prothrombin time, activated
      partial thromboplastin time, fibrinogen and platelet counts between the groups
      before surgery. Blood loss increased as the total withdrawn blood (sum of PABD
      and ANH) increased. CONCLUSION: Increased intraoperative blood loss was
      associated with total withdrawn blood before the operation as well as ANH.

PMID- 22483628
TI  - The importance of transmission time in HIV infections and an epidemiological
      prospective follow-up study for 1 year in the Marmara Region of Turkey.
AB  - It is important to detect recent and new HIV/1 infections and to take
      preventative measures in order to prevent rapid disease progression in AIDS and
      to decrease the incidence of infection. We aimed to detect long standing or
      recent HIV infections by determining transmission times for the cases in which
      first-time HIV/1 seropositivity were detected. The serum samples of 323 cases
      which were found to be seropositive by ELISA and Western-blotting were included
      in this study. The discrimination between long-term and recent HIV/1 infection
      was made by determining transmission-time with the Aware BED-EIA, HIV-1 incidence
      test (IgG capture HIV-EIA) tests. Ninety-six healthy blood donors who did not
      have a positive anti-HIV test and a chronic infectious disease for at least 1
      year were included in this study as a negative healthy control group. In the
      discrimination of long-term and recent HIV/1 infections, only in vitro ODn values
      were used. The cases with normalized optical density (OD)
      (OD(specimen)/OD(calibrator))<0.8 by commercial kit were accepted as recent HIV
      infection (155 days history or seroconversion less than 6 months). The cases with
      ODn >1.2 were accepted as long-term HIV/1 infections (more than 155 days history
      or more than 6 months). The cases with ODn between 0.8 and 1.2 were accepted as
      "additional tests needed" cases. We detected recent HIV/1 infections (<6 months)
      in 60 (18.5%) out of 323 cases and long-term HIV/1 infections (>6 months) in 263
      (81.5%) out of 323 cases. The most frequently encountered transmission route in
      long-term and recent HIV/1 infections was heterosexual sexual intercourse as 54
      (50%) and 257 (97%), respectively. 63.3% of newly infected patients were married
      females and 65.3% of recently infected patients were males. In conclusion, the
      detection of the high ratio of long-term HIV/1 infection cases (81.5%) compared
      to recent infections (18.5%) suggested to us, that the long standing cases may
      have some activities related with transmission of HIV/1 in the past. The
      detection of higher HIV/1-infections in individuals which had heterosexual sex
      and also in married males suggested that this situation poses a very great threat
      for the health of society.

PMID- 22483629
TI  - Proximal femoral nail antirotation (PFN-ATM) fixation of extra-capsular proximal
      femoral fractures in the elderly: retrospective study in 102 patients.
AB  - BACKGROUND: The best surgical strategy for extra-capsular proximal femoral
      fractures (PFFs) is controversial in the elderly. Poor bone quality and neck
      screw instability can adversely affect the results with currently available
      fixation devices, which predominantly consist in dynamic hip screw-plates and
      proximal reconstruction nails. HYPOTHESIS: The helical blade of the proximal
      femoral nail antirotation (PFN-ATM) achieves better cancellous bone compaction in
      the femoral neck, thereby decreasing the risk of secondary displacement.
      MATERIALS AND METHODS: We retrospectively reviewed consecutive cases of PFN-ATM
      fixation performed between 2006 and 2008 in 102 patients (75 females and 27
      males) with a mean age of 84.9 +/- 9.5 years (range, 70-100 years). Functional
      outcomes were assessed using the Parker Mobility Score. RESULTS: Mean follow-up
      in the 102 patients was 21.3 +/- 17.5 months (4-51 months). Fracture distribution
      in the AO classification scheme was A1, n=45; A2, n=41; and A3, n=16. At last
      follow-up, Parker Mobility Score values in the 65 survivors were 0-3, n=35; 4-6,
      n=11; and 7-9, n=19. Fracture union was consistently achieved, after a mean of
      10.3 +/- 3 weeks. Blade back-out allowed by the device design occurred in 16
      (15.7%) patients but caused pain due to screw impingement on the fascia lata in
      only five patients (of whom two underwent reoperation). Cephalic blade cut-out
      was noted in three (2.9%) patients, of whom one required reoperation because of
      acetabular penetration. Two hardware-related fractures were recorded. DISCUSSION:
      The new PFN-ATM device ensures reliable fixation with low mechanical complication
      rates. Although our data do not constitute proof that a helical blade is superior
      over a neck screw, they suggest a decreased rate of construct failure and may
      serve as a basis for a comparative study.

PMID- 22483630
TI  - Total hip revision using a cup design with a peg to treat severe pelvic bone
      defects.
AB  - When dealing with severe bone loss during acetabular revision of a total hip
      arthroplasty, it can be difficult to find a reliable anatomical structure to
      ensure high-quality primary fixation of the cup. Since 2003, we have been using
      an implant with a long peg that is anchored into the iliac isthmus. This
      structure is usually intact, even in the most severe situations of bone loss. The
      use of this specially designed component provides satisfactory mechanical
      reconstruction in cases that can be quite challenging (Paprosky and SOFCOT stage
      3). The length and postoperative care for the procedure remain the same and early
      weight bearing is possible. The specific principles applying to this procedure,
      along with the anatomical features of the iliac isthmus, the implantation
      technique and our initial results are described in detail.

PMID- 22483631
TI  - Induced membrane technique for reconstruction after bone tumor resection in
      children: a preliminary study.
AB  - AIM: Segmental long-bone defect due to tumor resection remains a challenge to
      treat. The induced membrane technique is a new alternative for biological
      reconstruction. During the first stage, a cement spacer is inserted after bone
      resection and stabilisation. The cement spacer is removed during a second stage
      procedure performed after chemotherapy, and cortico-cancellous bone autograft was
      placed in the biological induced chamber. The aim of this study was to assess
      preliminary results in eight children. PATIENTS AND METHODS: This prospective
      study included six girls and two boys, with a mean age of 12.1 years (range 9.5
      to 18) and treated for a mean 15 cm defect (range 10 to 22 cms) due to resection
      of osteosarcoma (n=4), Ewing sarcoma (n=3) and low grade sarcoma. All patients
      except one, were given pre- and postoperative chemotherapy. Surgery was performed
      for three patients with a distal femur tumor, two patients with a proximal tibial
      tumor and three patients who had proximal humerus, shaft of humerus and fibular
      tumors. Fixation was mainly performed with locking compression plate (n=4) and
      locked nail (n=2). The mean operating times for first and second step procedures
      were 4.8 and 4h respectively. The healing process was radiologically assessed.
      RESULTS: After a mean follow-up of 21.6 months (15 to 30), all patients were free
      of disease and seven had bony union. For the lower limb reconstructions, full
      weight bearing was possible after a mean of 116 days (range 90 to 150) following
      the second stage. Mean time to bone union was 4.8 months (1.5 to 10). The early
      Musculoskeletal Tumor Society (MSTS) score was 25.2/30 (range 20-30).
      Complications were: non-union (n=1), paradoxical graft resorption (n=1) requiring
      graft revision. CONCLUSION: This two stage procedure reduces the operating time
      during the first stage and it also reduces early complications. Rapid bone union
      is objectively obtained despite major bone resection and the patients receiving
      chemotherapy. SIGNIFICANCE: The induced membrane technique could be an excellent
      alternative for biological reconstruction after tumor resection in children.

PMID- 22483633
TI  - On the search for potential anti-Trypanosoma cruzi drugs: synthesis and
      biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic
      naphthoquinoidal compounds obtained by click chemistry reactions.
AB  - Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic
      para-naphthoquinones, five nor-beta-lapachone-based 1,2,3-triazoles, and several
      other naphthoquinonoid compounds were synthesized and evaluated against the
      infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas
      disease, continuing our screening program for new trypanocidal compounds. Among
      all the substances, 16-18, 23, 25-29 and 30-33 were herein described for the
      first time and fifteen substances were identified as more potent than the
      standard drug benznidazole, with IC(50)/24h values in the range of 10.9-101.5
      MUM. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important
      structures for further studies.

PMID- 22483634
TI  - Synthesis, characterization and biological activity of hydroxyl-bisphosphonic
      analogs of bile acids.
AB  - Bisphosphonates (BPs) are now the most widely used drugs for diseases associated
      with increased bone resorption, such as osteoporosis, and tumor bone diseases. A
      significant drawback of the BPs is their poor oral absorption that is enhanced by
      the presence of bile acid substituents in the bisphosphonate framework, with no
      toxic effects. A straightforward synthesis of bile acid-containing hydroxy
      bisphosphonates and a full characterization of these pharmaceutically important
      molecules, including an evaluation of affinity and the mechanism of binding to
      hydroxyapatite, is presented. The biological activity of bile acid-containing
      bisphosphonate salts was determined using the neutral-red assay on the L929 cell
      line and primary cultures of osteoclasts. The bioactivity of the new compounds
      was found superior than bisphosphonates of established activity.

PMID- 22483632
TI  - Computational analysis of structure-based interactions and ligand properties can
      predict efflux effects on antibiotics.
AB  - AcrA-AcrB-TolC efflux pumps extrude drugs of multiple classes from bacterial
      cells and are a leading cause for antimicrobial resistance. Thus, they are of
      paramount interest to those engaged in antibiotic discovery. Accurate prediction
      of antibiotic efflux has been elusive, despite several studies aimed at this
      purpose. Minimum inhibitory concentration (MIC) ratios of 32 beta-lactam
      antibiotics were collected from literature. 3-Dimensional Quantitative Structure
      Activity Relationship on the beta-lactam antibiotic structures revealed seemingly
      predictive models (q(2)=0.53), but the lack of a general superposition rule does
      not allow its use on antibiotics that lack the beta-lactam moiety. Since MIC
      ratios must depend on interactions of antibiotics with lipid membranes and
      transport proteins during influx, capture and extrusion of antibiotics from the
      bacterial cell, descriptors representing these factors were calculated and used
      in building mathematical models that quantitatively classify antibiotics as
      having high/low efflux (>93% accuracy). Our models provide preliminary evidence
      that it is possible to predict the effects of antibiotic efflux if the passage of
      antibiotics into, and out of, bacterial cells is taken into account--something
      descriptor and field-based QSAR models cannot do. While the paucity of data in
      the public domain remains the limiting factor in such studies, these models show
      significant improvements in predictions over simple LogP-based regression models
      and should pave the path toward further work in this field. This method should
      also be extensible to other pharmacologically and biologically relevant transport
      proteins.

PMID- 22483635
TI  - Chemical synthesis and biological evaluation of triazole derivatives as
      inhibitors of InhA and antituberculosis agents.
AB  - A series of triazoles have been prepared and evaluated as inhibitors of InhA as
      well as inhibitors of Mycobacterium tuberculosis H(37)R(v). Several of these new
      compounds possess a good activity against InhA, particularly compounds 17 and 18
      for which molecular docking has been performed. Concerning their activities
      against M. tuberculosis H(37)R(V) strain, two of them, 3 and 12, were found to be
      good inhibitors with MIC values of 0.50 and 0.25 MUg/mL, respectively.
      Particularly, compound 12 presenting the best MIC value of all compounds tested
      (0.6 MUM) is totally inactive against InhA.

PMID- 22483636
TI  - A new class of bioactivable self-immolative N,O-ligands.
AB  - A hexadentate ligand built on an amine-bis(phenol) skeleton with an aminal, self
      immolative moiety is presented. Synthesis of the ligand is convenient and
      relatively high yielded. Moreover, it enables synthesis of many derivatives, both
      in the amino-phenol and aminal fragment (various heterocycles). Once the final
      hexadentate ligand is synthesized via the Katritzky reaction, it becomes prone to
      hydrolysis. Bioactivation by beta-galactosidase cleaves the glycosylic bond and a
      spontaneous collapse of the aminal fragment occurs, thus leading to a
      pentadentate chelate. This bioactivation has been shown for pyrazole, 1,2,4
      triazole and benzotriazole derivatives.

PMID- 22483637
TI  - The toxicity of cadmium (Cd2+) towards embryos and pro-larva of soldatov's
      catfish (Silurus soldatovi).
AB  - A six-day static-renewal toxicity test was performed to determine the influences
      of cadmium on the development of embryos of soldatov's catfish (Silurus
      soldatovi). The median lethal concentration (LC50) value and median effective
      concentration (EC50, i.e., the total adverse effects, including developmental
      defects and mortality) were calculated to be 2740 and 133 MUg/L, respectively,
      when cadmium was prepared in dilution water. The LC50 decreased to 266 MUg/L in a
      subsequent test one month later, thereby suggesting that the sensitivity of this
      fish to cadmium in the early life stage(1) was largely influenced by the quality
      of fertilized eggs, which is known to be dependent on the season. The mortality
      and total adverse effects showed a concentration-dependent relationship at
      dosages greater than 1000 or 10 MUg/L (p<0.05), respectively, at pro-larva stage
      (i.e., 144 hpf) with dilution water. To compare the toxic effects of cadmium
      under field and experimental conditions, filtered river water was adopted as a
      solvent simultaneously compared with dilution water. No significant differences
      were observed in mortality rate, hatching rate and adverse effect prevalence
      between the two solvents. In comparison to previously published toxicity data for
      other fish, the pro-larva of soldatov's catfish were less sensitive than
      established test fish in the early life stage. Therefore, the environmental risks
      would be overestimated when considering only existing toxicity data for other
      test fish.

PMID- 22483638
TI  - Do interspecies correlation estimations increase the reliability of toxicity
      estimates for wildlife?
AB  - For warm-blooded species, the hazardous dose of a chemical (HD50) is an upcoming
      and important characteristic in the assessment of toxic chemicals. Generally,
      experimental information is available for a limited number of warm-blooded
      species only, which causes statistical uncertainty. Furthermore, when small
      datasets contain an unrepresentative sample of species, they can cause systematic
      uncertainty in chemicals' hazardous doses. The number of species can be enlarged
      with interspecies correlation estimation (ICE) models, but these are uncertain
      themselves. The goal of this study is to quantify the possible gain in
      reliability of the HD50 values for warm-blooded wildlife species after
      enlargement of the sample size with ICE predictions. For 1137 chemicals, we
      compared systematic uncertainty and statistical uncertainty between HD50 values
      based on experimental data (HD50(Ex)) and on datasets combining experimental data
      and ICE predictions (HD50(Co)). HD50(Ex) values ranged between 1.0*10(-1) and
      9.5*10(3)mgkg(wwt)(-1), and HD50(Co) values between 1.1*10(0) and
      6.1*10(3)mgkg(wwt)(-1). For over 97 percent of the chemicals, HD50(Ex) values
      exceeded HD50(Co) values, with a systematic uncertainty (i.e. the ratio of
      HD50(Ex)/HD50(Co)) of typically 3.5. The limited availability of experimental
      toxicity data, predominantly for mammals, resulted in a systematic
      underestimation of the wildlife toxicity of a chemical. Statistical uncertainty
      factors (i.e. the ratio of the 95th/5th percentile) quantified the statistical
      uncertainty in the HD50 values. The statistical uncertainty factors ranged
      between 1.0*10(0) and 2.5*10(22) for the experimental dataset, and between
      4.8*10(0) and 1.1*10(2) for the combined dataset. For all sample sizes, median
      statistical uncertainty factors were the largest for combined datasets. However,
      combining experimental toxicity data with ICE predictions makes it possible to
      reduce the upper limit of the range for statistical uncertainty factors. We
      conclude that, by combining experimental data with ICE model predictions, the
      validity of the HD50 value can be improved and high statistical uncertainty can
      be reduced, particularly in cases of limited toxicity data, i.e. data for mammals
      only or a sample size of n<=4.

PMID- 22483640
TI  - [Level of knowledge and acceptance of the anti-rotavirus vaccination by parents
      of children hospitalised due to gastroenteritis].

PMID- 22483639
TI  - Renal cell neoplasms contain shared tumor type-specific copy number variations.
AB  - Copy number variant (CNV) analysis was performed on renal cell carcinoma (RCC)
      specimens (chromophobe, clear cell, oncocytoma, papillary type 1, and papillary
      type 2) using high-resolution arrays (1.85 million probes). The RCC samples
      exhibited diverse genomic changes within and across tumor types, ranging from 106
      to 2238 CNV segments in a clear-cell specimen and in a papillary type 2 specimen,
      respectively. Despite this heterogeneity, distinct CNV segments were common
      within each tumor classification: chromophobe (seven segments), clear cell (three
      segments), oncocytoma (nine segments), and papillary type 2 (two segments).
      Shared segments ranged from a 6.1-kb deletion (oncocytomas) to a 208.3-kb
      deletion (chromophobes). Among common tumor type-specific variations,
      chromophobes, clear-cell tumors, and oncocytomas were composed exclusively of
      noncoding DNA. No CNV regions were common to papillary type 1 specimens, although
      there were 12 amplifications and 12 deletions in five of six samples. Three
      microRNAs and 12 mRNA genes had a >=98% coding region contained within CNV
      regions, including multiple gene families (chromophobe: amylases 1A, 1B, and 1C;
      oncocytoma: general transcription factors 2H2, 2B, 2C, and 2D). Gene deletions
      involved in histone modification and chromatin remodeling affected individual
      subtypes (clear cell: SFMBT and SETD2; papillary type 2: BAZ1A) and the
      collective RCC group (KDM4C). The genomic amplifications/deletions identified
      herein represent potential diagnostic and/or prognostic biomarkers.

PMID- 22483641
TI  - Near infrared spectroscopy and multivariate calibration for simultaneous
      determination of glucose, triglycerides and high-density lipoprotein in animal
      plasma.
AB  - The quantitative analysis of glucose, triglycerides and high-density lipoprotein
      (HDL) in rat plasma without sample pre-treatment using direct near-infrared
      spectroscopy was studied. Comparison was made of several multivariate calibration
      techniques and algorithms for data pre-processing and variable selection,
      including partial least squares (PLS), interval partial least squares (iPLS),
      genetic algorithm (GA) and successive projections algorithm (SPA). Variable
      selection yielded good results for the correlation coefficient and Root Mean
      Square Error of Prediction (RMSEP) values for the three parameters, especially
      triglycerides. The RMSEP values for glucose, triglycerides and HDL produced by
      the PLS model were 6.08, 16.07 and 2.03 mg dl(-1), respectively. F tests and t
      tests were performed to compare the results of the models with each other and
      with a reference method. These results suggests that the PLS method can be used
      to simultaneously determine the concentrations of glucose, triglycerides and HDL
      in complicated biological fluids with NIR spectroscopy, offering an alternative
      analysis in animals.

PMID- 22483642
TI  - A validated HPLC assay for the determination of R-(-)-gossypol in human plasma
      and its application in clinical pharmacokinetic studies.
AB  - R-(-)-gossypol acetic acid (AT-101), a natural BH3 mimetic, is investigated in a
      Phase I/II clinical trial for the treatment of advanced solid tumor malignancies.
      Gossypol undergoes rapid degradation in solution phase, which causes major
      technical difficulty for its quantitation in plasma. We developed and validated a
      sensitive HPLC assay for pharmacokinetic evaluation of gossypol. Acetonitrile
      deproteinization method was chosen for sample preparation and Schiff's base
      derivative, R-(-)-gossypol-diamino-propanol (GDP), was used as internal standard.
      Chromatographic separation of gossypol in plasma was performed using a Zorbax
      Eclipse XDB column C(18) at 30  degrees C. The mobile phase consists of 10 mmol/L
      KH(2)PO(4) (pH 3.0) and acetonitrile (20:80) at 1.0 mL/min flow rate. Linearity
      ranged over 56-3585 ng/mL (R(2)=0.9997+/-0.0003, n=4), and the limit of detection
      was 28 ng/mL. The intra- and inter-assay precision was less than 13.7% and the
      bias ranged from -7.4 to 7.0%. The method was successfully applied to
      characterize the pharmacokinetics of AT-101 in a Phase I clinical trial. The
      validated assay is accurate, and sensitive with minimum loss and rapid analysis
      time and suitable for quantification of gossypol for pharmacokinetics evaluation.

PMID- 22483643
TI  - Using a standardized assessment tool to measure patient experience on a seizure
      monitoring unit compared to a general neurology unit.
AB  - Seizure monitoring unit (SMU) research typically focuses on diagnostic utility
      and medical management of epilepsy. However, patient safety and satisfaction are
      also imperative to high-quality SMU care. This study uses a standardized tool to
      evaluate patient experience on a SMU compared to a general neurology unit (GNU).
      The 27-item Hospital Consumer Assessment of Healthcare Providers and Systems
      (HCAHPS) survey was telephone-administered post-discharge to a sample of patients
      from our SMU and GNU. Data from a 33-month period were reviewed, encompassing 217
      SMU patient admissions and 317 GNU patient admissions. On average, SMU patients
      were 14.7 years younger and stayed in the hospital 4.2 days longer than GNU
      patients. SMU patients provided lower overall mental health ratings (p<.001),
      perceived nursing staff to be more responsive to the call button (p<.001), and
      assigned higher overall ratings to their stay (p<0.05). Lower education was
      associated with more favorable hospital ratings on both units (p<0.05).

PMID- 22483644
TI  - The NAB shape learning subtest as a predictor of lateralized seizure onset.
AB  - This study presents the first empirical evaluation of the predictive value of the
      Neuropsychological Assessment Battery Shape Learning (NAB-SL) subtest in a sample
      of patients with unilateral temporal lobe epilepsy. Stimulus characteristics of
      the NAB-SL may improve predictive ability over other commonly used visual memory
      tests. Forty-nine patients with unilateral temporal lobe epilepsy were compared
      on measures of non-verbal and verbal memory (NAB-SL and Wechsler Memory Scale-III
      subtests). Univariate and forward conditional logistic regressions identified
      predictive values for each memory test individually and in combination. The NAB
      SL delayed memory demonstrated consistently stronger predictive power over visual
      reproduction at the univariate and multivariate levels. The NAB-SL was a good
      predictor (80% range) of lateralized seizure onset when combined with a verbal
      memory measure. These preliminary results provide support for the use of the NAB
      SL in preoperative epilepsy evaluations as a predictor of non-dominant temporal
      lobe dysfunction. Potential benefits of this test are discussed.

PMID- 22483645
TI  - A female adult with Sandifer's syndrome and hiatal hernia misdiagnosed as
      epilepsy with focal seizures.
AB  - Sandifer's syndrome is a rare, probably underdiagnosed, and usually pediatric
      movement disorder associated with gastroesophageal reflux disease. Often, it is
      misdiagnosed as epilepsy or paroxysmal dyskinesia. We report the case of an adult
      female with Sandifer's syndrome initially diagnosed as focal epilepsy and treated
      inefficiently with anticonvulsants for two years.

PMID- 22483646
TI  - Anticonvulsant activity of bisabolene sesquiterpenoids of Curcuma longa in
      zebrafish and mouse seizure models.
AB  - Turmeric, obtained from the rhizomes of Curcuma longa, is used in South Asia as a
      traditional medicine for the treatment of epilepsy. To date, in vivo studies on
      the anticonvulsant activity of turmeric have focused on its principal
      curcuminoid, curcumin. However, poor absorption and rapid metabolism have limited
      the therapeutic application of curcumin in humans. To explore the therapeutic
      potential of turmeric for epilepsy further, we analyzed its anticonvulsant
      activity in a larval zebrafish seizure assay. Initial experiments revealed that
      the anticonvulsant activity of turmeric in zebrafish larvae cannot be explained
      solely by the effects of curcumin. Zebrafish bioassay-guided fractionation of
      turmeric identified bisabolene sesquiterpenoids as additional anticonvulsants
      that inhibit PTZ-induced seizures in both zebrafish and mice. Here, we present
      the first report of the anticonvulsant properties of bisabolene sesquiterpenoids
      and provide evidence which warrants further investigation toward the mechanistic
      understanding of their neuromodulatory activity.

PMID- 22483648
TI  - Risk of death associated with use of PPIs in three cohorts of institutionalized
      older people in Finland.
AB  - OBJECTIVES: To (1) explore clinical and demographic characteristics of users and
      nonusers of PPIs in 3 cohorts of institutionalized older people in Finland, and
      (2) compare the risk of death associated with use of PPIs in each setting.
      DESIGN: Cross-sectional assessment of 3 institutionalized cohorts with 1-year
      follow-up of all-cause mortality. SETTING AND PARTICIPANTS: A total of 1389
      residents of 69 assisted living facilities (first cohort), 1004 residents of long
      term care hospitals (second cohort), and 425 residents in acute geriatric wards
      or in nursing homes (third cohort). MEASUREMENTS: Demographic, drug use, and
      diagnostic data were collected during structured assessments conducted by trained
      nurses or geriatricians. Cox proportional hazards models were used to compute
      unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs)
      for the association between use of PPIs and mortality. RESULTS: In the assisted
      living facility, the mortality was 20.2% (n = 74) and 20.4% (n = 208) among users
      and nonusers of PPIs, respectively (P = 0.94). PPIs were not associated with
      mortality in unadjusted or adjusted analyses. In the long term care hospitals,
      use of PPIs was associated with increased mortality (HR, 1.36; 95% CI 1.04-1.77)
      when adjusted for age, sex, comorbidity, use of SSRIs, and malnutrition. In the
      acute geriatric wards and nursing homes, use of PPIs was associated with
      increased mortality (HR, 1.90; 95% CI 1.23-2.94) when adjusted for age, sex,
      comorbidity, delirium, and use of aspirin and SSRIs. CONCLUSION: PPIs were not
      associated with mortality among residents in assisted living facilities, but were
      associated with increased mortality in settings where residents experienced
      higher levels of disability and possible susceptibility to adverse drug events.

PMID- 22483647
TI  - Exploring the role of copy number variants in human adaptation.
AB  - Over the past decade, the ubiquity of copy number variants (CNVs, the gain or
      loss of genomic material) in the genomes of healthy humans has become apparent.
      Although some of these variants are associated with disorders, a handful of
      studies documented an adaptive advantage conferred by CNVs. In this review, we
      propose that CNVs are substrates for human evolution and adaptation. We discuss
      the possible mechanisms and evolutionary processes in which CNVs are selected,
      outline the current challenges in identifying these loci, and highlight that copy
      number variable regions allow for the creation of novel genes that may diversify
      the repertoire of such genes in response to rapidly changing environments. We
      expect that many more adaptive CNVs will be discovered in the coming years, and
      we believe that these new findings will contribute to our understanding of human
      specific phenotypes.

PMID- 22483650
TI  - Bluetongue sentinel surveillance program and cross-sectional serological survey
      in cattle in Belgium in 2010-2011.
AB  - Bluetongue virus serotype 8 (BTV-8) emerged in Central Western Europe in 2006
      causing a large scale epidemic in 2007 that involved several European Union (EU)
      countries including Belgium. As in several other EU member states, vaccination
      against BTV-8 with inactivated vaccines was initiated in Belgium in spring 2008
      and appeared to be successful. Since 2009, no clinical cases of Bluetongue (BT)
      have been reported in Belgium and BTV-8 circulation seemed to have completely
      disappeared by spring 2010. Therefore, a series of repeated cross-sectional
      surveys, the BT sentinel surveillance program, based on virus detection in blood
      samples by means of real-time RT-PCR (RT-qPCR) were carried out in dairy cattle
      from the end of 2010 onwards with the aim to demonstrate the absence of BTV
      circulation in Belgium. This paper describes the results of the first two
      sampling rounds of this BT sentinel surveillance program carried out in October
      November 2010 and January-February 2011. In addition, the level of BTV-specific
      maternal antibodies in young non-vaccinated animals was monitored and the level
      of herd immunity against BTV-8 after 3 consecutive years of compulsory BTV-8
      vaccination was measured by ELISA. During the 1st sampling round of the BT
      sentinel surveillance program, 15 animals tested positive and 2 animals tested
      doubtful for BTV RNA by RT-qPCR. During the 2nd round, 17 animals tested positive
      and 5 animals tested doubtful. The positive/doubtful animals in both rounds were
      re-sampled 2-4 weeks after the original sampling and then all tested negative by
      RT-qPCR. These results demonstrate the absence of BTV circulation in Belgium in
      2010 at a minimum expected prevalence of 2% and 95% confidence level. The study
      of the maternal antibodies in non-vaccinated animals showed that by the age of 7
      months maternal antibodies against BTV had disappeared in most animals. The BTV
      seroprevalence at herd level after 3 years of compulsory BTV-8 vaccination was
      very high (97.4% [95% CI: 96.2-98.2]). The overall true within-herd BTV
      seroprevalence in 6-24 month old Belgian cattle in early 2011 was estimated at
      73.4% (95% CI: 71.3-75.4).

PMID- 22483651
TI  - Efficacy and pitfalls of transapical cannulation for the repair of acute type A
      aortic dissection.
AB  - BACKGROUND: Selection of a cannulation site for the repair of acute type A aortic
      dissection remains controversial. Several cannulation sites have been introduced,
      but each is associated with a risk of adverse complications. Transapical
      cannulation is a simple procedure to restore antegrade blood flow during ECC.
      However the efficacy of this procedure is unknown. METHODS: Among 400 patients
      undergoing surgical repair of acute type A dissection at Sakakibara Heart
      Institute between 2003 and 2010, transapical cannulation was performed in 52
      patients, and these patients were included in this study. Transapical cannulation
      was selected as the initial cannulation site in 44 patients and as conversion
      from femoral cannulation in 8 patients. RESULTS: There were 4 in-hospital
      mortalities (mortality rate, 7.7%) and 5 patients had strokes (stroke rate,
      9.6%). Transapical cannulation was successful in 47 patients (90.4%). Conversion
      of the cannulation site was necessary in 5 patients: Malperfusion on initiation
      of ECC was observed in 4 patients and emergence of aortic regurgitation was
      observed in 1 patient. The cannula was moved to another artery for correction in
      these patients. There was no mortality in patients undergoing conversion of the
      cannulation site. CONCLUSIONS: Transapical cannulation is considered an effective
      option for the repair of acute type A aortic dissection. Transapical cannulation
      cannot eliminate the risk of intraoperative malperfusion, and therefore careful
      assessment with intraoperative monitoring is necessary.

PMID- 22483652
TI  - Anatomic segmentectomy for the solitary pulmonary nodule and early-stage lung
      cancer.
AB  - BACKGROUND: Anatomic segmentectomy is a versatile sublobar resection approach
      that can be both diagnostic and therapeutic in the setting of the indeterminate
      pulmonary nodule (IPN), metastasectomy, as well as small, peripheral cancers. We
      analyzed the clinical indications and perioperative outcomes after anatomic
      segmentectomy and explored its utility in the diagnosis and treatment of IPNs and
      small stage IA lung cancers. METHODS: This study is a retrospective review of 785
      consecutive patients undergoing anatomic segmentectomy from 2002 to 2010. Primary
      outcome variables include perioperative course, morbidity, mortality, recurrence
      patterns, and survival. RESULTS: Surgical indications included IPN (62.4%), known
      lung cancer (27.6%), suspected metastasis (4.1%), bullous disease (3.7%), or
      other (2.2%). Video-assisted thoracic surgery was employed in 468 (59.6%) and
      open thoracotomy in 317 (40.4%) patients. Median length of stay was 6 days.
      Overall complication rate was 34.9%. Thirty-day mortality was 1.1%. Among 490
      patients with an IPN, 381 (77.7%) were found to have lung cancer, 41 (8.4%)
      metastatic cancer, and 68 (13.9%) benign disease. Among patients with pathologic
      stage IA lung cancer, there was no difference in recurrence rates (14.5% vs
      13.9%) or 5-year freedom from recurrence estimates (78% in each group, p=0.738)
      when comparing segmentectomy and lobectomy. CONCLUSIONS: Anatomic segmentectomy
      provides acceptable morbidity and mortality when approaching the IPN. Cancer is
      identified in 86% of lesions. Complete surgical resection can be achieved with
      generous parenchymal margins and thorough nodal staging for small, peripheral
      stage IA non-small cell lung cancer. The use of anatomic segmentectomy should be
      considered in this era of competing image-guided diagnostic and therapeutic
      approaches to peripheral lung pathology.

PMID- 22483653
TI  - Toward a modern delivery of stroke care in emerging economies.
AB  - Noncommunicable diseases are now a major source of mortality and disability in
      the developing world. Stroke incidence and prevalence is on the rise and is of
      particular interest because of its elevated mortality and morbidity. Developing
      countries bear the brunt of this disease, which hampers efforts to achieve
      economic and societal growth. Effective strategies to control this disease should
      focus on prevention without neglecting acute therapies. 

PMID- 22483654
TI  - Perspectives in Rheumatoid Abstracts from 2011 meeting selected proceedings of
      the 4(th) Annual Perspectives in Rheumatic Diseases 2011.

PMID- 22483655
TI  - Introduction: the value in musculoskeletal care editorial/introduction to summary
      and recommendations.

PMID- 22483656
TI  - The value in musculoskeletal care: summary and recommendations.

PMID- 22483657
TI  - Pneumococcal vaccine in patients with rheumatoid arthritis.

PMID- 22483658
TI  - A male patient with cavitary pulmonary disease.
AB  - Granulomatosis with polyangiitis (Wegener) (GPA) was diagnosed in a 44 year-old
      man who had a relapse 6 years after diagnosis with the "air crescent" sign on
      chest CT. Seven years after his diagnosis the patient presented a new relapse
      with cavitary lung disease, and high levels of anti-proteinase 3 antibodies,
      suggesting disease activity; however, a transbronchial biopsy showed histological
      findings of tuberculosis (TB). The association between TB and GPA is rarely
      informed; moreover TB and GPA have similar findings including both clinical and
      anti-proteinase 3 antibodies.

PMID- 22483659
TI  - Serum cystatin C as a marker of renal function in patients with systemic lupus
      erythematosus.

PMID- 22483660
TI  - Large granular lymphocyte leukemia as a complication of rheumatoid arthritis.
AB  - Large granular lymphocyte leukemia is a rare entity belonging to same spectrum of
      diseases than Felty's syndrome, which might occur in patients with long-standing
      rheumatoid arthritis. It is clinically characterized by persistent neutropenia
      and recurrent bacterial infections associated with the presence in both
      peripheral blood and bone marrow of clonal expansion of atypic lymphocytes with a
      cytotoxic T cell phenotype, or less frequently an NK-cell phenotype, as well as
      splenomegaly. It is more frequently diagnosed in seropositive rheumatoid
      arthritis, with significant structural damage, extra-articular manifestations and
      persistently elevated values of ESR, despite them havubg low inflammatory joint
      activity. We report the case of a 70 year old male with a long-standing
      rheumatoid arthritis, who developed septic shock secondary to prosthetic hip
      infection by Salmonella spp. He showed persistent neutropenia, and an aberrant
      monoclonal T cell population was detected in both peripheral blood and bone
      marrow, consistent with large granular lymphocyte leukemia.

PMID- 22483661
TI  - New therapeutic targets in systemic lupus.
AB  - Glucocorticoids, aspirin, antimalarials and conventional immunosuppressants are
      the mainstay of treatment of Systemic Lupus Erythematosus (SLE). Until recently,
      the first three were the only agents approved for treatment. A better
      understanding of the pathophysiology of the immune system has identified new
      therapeutic targets. In fact, belimumab, a human monoclonal antibody to BLyS
      inhibitor has become, in recent months, the first drug approved for the treatment
      of SLE since 1957, underscoring difficulties of all kinds, including economic and
      organizational ones inherent to clinical trials on this disease. Many other
      molecules are in various stages of development and soon will have concrete
      results. In this review, we examined the mechanism of action and most relevant
      clinical data for these molecules.

PMID- 22483662
TI  - Fibromyalgia Health Assessment Questionnaire: sensitivity to change.
AB  - OBJECTIVE: To analyze the responsiveness of the Fibromyalgia Health Assessment
      Questionnaire (FHAQ) in a group of patients with fibromyalgia (FM). METHODS:
      Observational, prospective and longitudinal study related to the project ICAF was
      taken part in 15 Spanish centers. 232 patients were included and diagnosed of FM:
      98.3% were women, the mean age was 47 years old, they were analyzed at a basal
      visit and 3 months visit, afterwards an appropriated treatment was prescribed.
      The statistical analysis was performed including: mean comparison, mean
      standardized response (RME), basal standard media (DE), intraclass correlation
      coefficient (R), standard error of the mean (EEM), minimal detectable difference
      (DMD) and percentage change in real. RESULTS: The difference in mean comparison
      of the FHAQ in the baseline visit and the 3 months visit was of 0.098 (95% CI:
      0.034-0.16), with a P<.003. Nevertheless the RME was 0.21, a slightly change, the
      DE=0.57, R=0.81, EEM=0.25, and the DMD=0.69. The percentage change in real was
      17% (39 patients). But the sense of the change was positive in 28 cases (less
      punctuation in the 3 months visit) and negative in other 11 cases (higher
      punctuation in the 3 months visit). CONCLUSIONS: The punctuation in the 3 months
      visit was significant better than the basal, but the results of this study do not
      let it to consider that the FHAQ have enough change susceptibility to recommend
      it in longitudinal studies. The well knowing fact, some patients can become worse
      with the treatment prescribed would be to the detriment of the FHAQ psychometric
      value.

PMID- 22483663
TI  - Facticial panniculitis and Lofgren's syndrome: a case.
AB  - We herein report a patient who came to the hospital because of a polyarticular
      joint pain, fever and cutaneous lesions. She had silicone implants in her
      buttocks, a surgery performed 3 years before. We made a biopsy of the skin of the
      buttocks (facticial panniculitis due to silicone) and of the pretibial surface of
      the inferior extremities (erythema nodosum). A chest X- ray and a CT scan
      revealed bilateral hiliar lymphadenopathy, and a transbronquial biopsy showed
      granulomatous inflammation. She had a good response to rest and anti-inflammatory
      drugs, so the removal of the silicone implants has not been necessary yet.

PMID- 22483664
TI  - New targets in systemic lupus (part 2/2).
AB  - Glucocorticoids, aspirin, conventional antimalarials and immunosuppressants are
      the mainstay of treatment of Systemic Lupus Erythematosus (SLE). Until recently,
      the first three were the only agents approved for treatment. A better
      understanding of the pathophysiology of the immune system has identified new
      therapeutic targets. In fact, belimumab, a human monoclonal antibody to BLyS
      inhibitor has become, in recent months, the first drug approved for the treatment
      of SLE since 1957, underscoring difficulties of all kinds, including economic and
      organizational ones inherent to clinical trials on this disease. Many other
      molecules are in various stages of development and soon will have concrete
      results. In this review, we examined the mechanism of action and most relevant
      clinical data for these molecules.

PMID- 22483665
TI  - Hendra and Nipah viruses: why are they so deadly?
AB  - Henipavirus, including Hendra and Nipah viruses, is a group of emerging bat-borne
      paramyxoviruses which were responsible for severe disease outbreaks in humans,
      horses and pigs. The mortality rate of human infection varies between 50 and
      100%, making them one of the most deadly viruses known to infect humans. Its use
      of highly conserved cell surface molecules (ephrin) as entry receptors and its
      highly effective replication and fusion strategies are believed to be important
      characteristics responsible for its high pathogenicity. Henipavirus also encodes
      multiple accessory proteins which play a key role in evasion of host innate
      immune responses. Our recent study on the mechanism of IFN antagonism by
      henipaviruses indicated that a better understanding of the virus-host interaction
      provides great potential to develop new therapeutic strategies against these
      viruses.

PMID- 22483666
TI  - Why has nature invented three stop codons of DNA and only one start codon?
AB  - We examine the standard genetic code with three stop codons. Assuming that the
      synchronization period of length 3 in DNA or RNA is violated during the
      transcription or translation processes, the probability of reading a frameshifted
      stop codon is higher than if the code would have only one stop codon.
      Consequently, the synthesis of RNA or proteins will soon terminate. In this way,
      cells do not produce undesirable proteins and essentially save energy. This
      hypothesis is tested on the AT-rich Drosophila genome, where the detection of
      frameshifted stop codons is even higher than the theoretical value. Using the
      binomial theorem, we establish the probability of reading a frameshifted stop
      codon within n steps. Since the genetic code is largely redundant, there is still
      space for some hidden secondary functions of this code. In particular, because
      stop codons do not contain cytosine, random C -> U and C -> T mutations in the
      third position of codons increase the number of hidden frameshifted stops and
      simultaneously the same amino acids are coded. This evolutionary advantage is
      demonstrated on the genomes of several simple species, e.g. Escherichia coli.

PMID- 22483667
TI  - The role of Acinetobacter in the pathogenesis of multiple sclerosis examined by
      using Popper sequences.
AB  - Multiple sclerosis (MS) is an autoimmune neurological disorder. The role of
      'Acinetobacter' has been examined using the method of Karl Popper and involves
      nine "Popper sequences". (1) The frequency of MS increases with latitudes in the
      Northern Hemisphere, and the reverse is found in the Southern Hemisphere. (2)
      Sinusitis is found frequently at colder latitudes. (3) Sinusitis occurs
      frequently in patients with MS. (4) Specific sequences of bovine myelin when
      injected into experimental animals will produce a neurological disorder
      resembling MS which is called "experimental allergic encephalomyelitis". (5)
      Computer analysis of myelin shows molecular mimicry with sequences found in
      Acinetobacter. (6) Antibodies to Acinetobacter bacteria are found in MS patients.
      (7) Acinetobacter bacteria are located on human skin and in the nasal sinuses.
      (8) IgA antibodies are preferentially elevated in the sera of MS patients,
      thereby suggesting the trigger microbe is acting across a mucosal surface
      probably located in the nasal sinuses. (9) Only Acinetobacter bacteria and no
      other microbes evoke statistically significant titres of antibodies in MS
      patients. These nine Popper sequences suggest that MS is most probably caused by
      infections with Acinetobacter bacteria in the nasal sinuses, and this could have
      therapeutic implications.

PMID- 22483668
TI  - Global panic reaction II - a 7-step repetitive vicious circle.
AB  - The GPR-II model describes a "7-step" panic model. In this model, the single
      panic patient is not only affected as single member. The pressure weighing on him
      is not only exerted by external factors but also by group members of his network.
      Therefore, he has to cope with his individual problems and with the expectations
      of all members. The "therapeutic" model of instant sedation used (rescue screens)
      and long-lasting steps (behavioural therapy in group models) are not appropriate
      to treat the patients successfully.

PMID- 22483669
TI  - Voltammetric and RP-LC assay for determination of benidipine HCl.
AB  - The detailed electrooxidative behavior of benidipine (BEN) has been studied by
      using glassy carbon (GC) and boron-doped diamond (BDD) electrodes. Using cyclic
      voltammetry, depending on the pH values and the working electrodes, BEN showed
      one or two sharp and irreversible oxidation responses. The voltammetric
      experiments on some model compounds allowed elucidation of the oxidation
      mechanism of BEN. Highly sensitive, selective, rapid, and fully validated
      voltammetric methods for the determination of BEN in tablet dosage form were also
      presented. Under optimized conditions, the peak current showed a linear
      dependence with concentration in the range between 3.25 MUg mL(-1) and 54.20 MUg
      mL(-1) for GC and 1.08 MUg mL(-1) and 54.20 MUg mL(-1) for BDD electrodes by
      using differential pulse (DPV) and square wave (SWV) voltammetric techniques. In
      this study, acid dissociation constant (pK(a)) value of BEN was determined by
      using the dependence of the retention factor on the pH of the mobile phase using
      reverse phase-liquid chromatographic (RP-LC) method. The effect of the
      composition of the mobile phase on the ionization constant was studied by
      measuring the pK(a) at different acetonitrile-water mixtures, ranging between 50
      and 65% (v/v). Also simple, accurate, precise and fully validated RP-LC method
      for the assay of BEN in dosage form has been developed. XTerra RP-18 column at 25
      degrees C with the mobile phase of acetonitrile:water 55:45 (v/v) adjusted to pH
      3.0 with 15 mM o-phosphoric acid was used. Isocratic elution was performed in
      less than 5.0 min with a flow rate of 1.0 mL min(-1). The RP-LC method allowed
      quantitation over the 0.25-15.00 MUg mL(-1) range for BEN. The proposed
      voltammetric and RP-LC methods allow a number of cost and time saving benefits.
      BEN was also exposed to thermal, photolytic, oxidative stress, acid-base
      catalyzed hydrolyses, and the stressed samples were detected by the proposed RP
      LC method.

PMID- 22483671
TI  - X inactivation in females with X-linked Charcot-Marie-Tooth disease.
AB  - X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common inherited
      neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a
      uniformly moderately severe phenotype while females have a variable phenotype,
      suggested to be due to X inactivation. We aimed to assess X inactivation pattern
      in females with CMT1X and correlate this with phenotype using the CMT examination
      score to determine whether the X inactivation pattern accounted for the variable
      phenotype in females with CMT1X. We determined X inactivation pattern in 67
      females with CMT1X and 24 controls using the androgen receptor assay. We were
      able to determine which X chromosome carried the GJB1 mutation in 30 females.
      There was no difference in X inactivation pattern between patients and controls.
      In addition, there was no correlation between X inactivation pattern in blood and
      phenotype. A possible explanation for these findings is that the X inactivation
      pattern in Schwann cells rather than in blood may explain the variable phenotype
      in females with CMT1X.

PMID- 22483672
TI  - Negotiating complementary and alternative medicine use in primary care visits
      with older patients.
AB  - OBJECTIVE: To empirically investigate the ways in which patients and providers
      discuss Complementary and Alternative Medicine (CAM) treatment in primary care
      visits. METHODS: Audio recordings from visits between 256 adult patients aged 50
      years and older and 28 primary care physicians were transcribed and analyzed
      using discourse analysis, an empirical sociolinguistic methodology focusing on
      how language is used to negotiate meaning. RESULTS: Discussion about CAM occurred
      128 times in 82 of 256 visits (32.0%). The most frequently discussed CAM
      modalities were non-vitamin, non-mineral supplements and massage. Three physician
      patient interactions were analyzed turn-by-turn to demonstrate negotiations about
      CAM use. Patients raised CAM discussions to seek physician expertise about
      treatments, and physicians adopted a range of responses along a continuum that
      included encouragement, neutrality, and discouragement. Despite differential
      knowledge about CAM treatments, physicians helped patients assess the risks and
      benefits of CAM treatments and made recommendations based on patient preferences
      for treatment. CONCLUSION: Regardless of a physician's stance or knowledge about
      CAM, she or he can help patients negotiate CAM treatment decisions. PRACTICE
      IMPLICATIONS: Providers do not have to possess extensive knowledge about specific
      CAM treatments to have meaningful discussions with patients and to give patients
      a framework for evaluating CAM treatment use.

PMID- 22483673
TI  - [Are there more ethical conflicts in times of economic crisis?].

PMID- 22483674
TI  - A varying patient safety profile between black and nonblack adults with decreased
      estimated GFR.
AB  - BACKGROUND: Chronic kidney disease is a high-risk condition for a variety of
      adverse safety events, yet little is known about differential rates of safety
      events across racial groups with decreased kidney function. We sought to examine
      the incidence of an array of disease-specific adverse safety events in black
      versus nonblack patients with decreased estimated glomerular filtration rate
      (eGFR). STUDY DESIGN: Retrospective observational study of a national US Veterans
      Affairs cohort. SETTINGS & PARTICIPANTS: Veterans with eGFR <60 mL/min/1.73 m(2)
      and one or more hospitalization during federal fiscal year 2005 (n = 70,154).
      PREDICTOR: Self-reported race/ethnicity dichotomized as black or nonblack.
      OUTCOMES: Hospital discharge coding for Agency for Healthcare Research and
      Quality (AHRQ) patient safety indicators (PSIs), laboratory records for detection
      of hyperkalemia and hypoglycemia, and pharmacy records to determine dosing of 4
      selected medications. MEASUREMENTS: Relationship between race and disease
      specific patient safety events. RESULTS: Black veterans were more likely than
      nonblack veterans to experience one type of safety event (33% vs 32%,
      respectively) and multiple types of safety events (32% vs 23%, respectively; both
      P < 0.001). After adjustment, black veterans were 11% and 36% more likely to have
      at least one episode of hyperkalemia and hypoglycemia, respectively, than
      nonblack veterans, but were 14% less likely to experience a medication error (all
      P < 0.001). There was no association between the occurrence of AHRQ PSIs and race
      after adjustment. LIMITATIONS: Use of administrative data has a risk of
      imprecision in coding; Veterans Affairs cohort may limit generalizability.
      CONCLUSIONS: Black veterans with decreased eGFR are more likely to experience a
      broad array of safety events than nonblacks with decreased eGFR, with a
      preponderance of metabolic disturbances rather than medication errors or AHRQ
      PSIs. The differential safety phenotype in blacks versus nonblacks may have
      implications for preventive strategies to improve patient safety in an integrated
      health care system.

PMID- 22483675
TI  - The PET-boost randomised phase II dose-escalation trial in non-small cell lung
      cancer.
AB  - PURPOSE: The local site of relapse in non-small cell lung cancer (NSCLC) is
      primarily located in the high FDG uptake region of the primary tumour prior to
      treatment. A phase II PET-boost trial (NCT01024829) randomises patients between
      dose-escalation of the entire primary tumour (arm A) or to the high FDG uptake
      region inside the primary tumour (>50% SUV(max)) (arm B), whilst giving 66 Gy in
      24 fractions to involved lymph nodes. We analysed the planning results of the
      first 20 patients for which both arms A and B were planned. METHODS: Boost dose
      levels were escalated up to predefined normal tissue constraints with an equal
      mean lung dose in both arms. This also forces an equal mean PTV dose in both
      arms, hence testing pure dose-redistribution. Actual delivered treatment plans
      from the ongoing clinical trial were analysed. Patients were randomised between
      arms A and B if dose-escalation to the primary tumour in arm A of at least 72 Gy
      in 24 fractions could be safely planned. RESULTS: 15/20 patients could be
      escalated to at least 72 Gy. Average prescribed fraction dose was 3.27+/-0.31 Gy
      [3.01-4.28 Gy] and 3.63+/-0.54 Gy [3.20-5.40 Gy] for arms A and B, respectively.
      Average mean total dose inside the PTV of the primary tumour was comparable:
      77.3+/-7.9 Gy vs. 77.5+/-10.1 Gy. For the boost region dose levels of on average
      86.9+/-14.9 Gy were reached. No significant dose differences between both arms
      were observed for the organs at risk. Most frequent observed dose-limiting
      constraints were the mediastinal structures (13/15 and 14/15 for arms A and B,
      respectively), and the brachial plexus (3/15 for both arms). CONCLUSION: Dose
      escalation using an integrated boost could be achieved to the primary tumour or
      high FDG uptake regions whilst keeping the pre-defined dose constraints.

PMID- 22483676
TI  - Credentialing of radiotherapy centres for a clinical trial of adaptive
      radiotherapy for bladder cancer (TROG 10.01).
AB  - BACKGROUND: Daily variations in bladder filling make conformal treatment of
      bladder cancer challenging. On-line adaptive radiotherapy with a choice of plans
      has been demonstrated to reduce small bowel irradiation in single institution
      trials. In order to support a multicentre feasibility clinical trial on adaptive
      radiotherapy for bladder cancer (TROG 10.01) a credentialing programme was
      developed for centres wishing to participate. METHODS: The credentialing
      programme entails three components: a facility questionnaire; a planning exercise
      which tests the ability of centres to create three adaptive plans based on a
      planning and five cone beam CTs; and a site visit during which image quality,
      imaging dose and image guidance procedures are assessed. Image quality and
      decision making were tested using customised inserts for a Perspex phantom (Modus
      QUASAR) that mimic different bladder sizes. Dose was assessed in the same phantom
      using thermoluminescence dosimetry (TLD). RESULTS: All 12 centres participating
      in the full credentialing programme were able to generate appropriate target
      volumes in the planning exercise and identify the correct target volume and
      position the bladder phantom in the phantom within 3mm accuracy. None of the
      imaging doses exceeded the limit of 5 cGy with a CT on rails system having the
      lowest overall dose. CONCLUSION: A phantom mimicking the decision making process
      for adaptive radiotherapy was found to be well suited during site visits for
      credentialing of centres participating in a clinical trial of adaptive
      radiotherapy for bladder cancer. Combined with a planning exercise the site visit
      allowed testing the ability of centres to create adaptive treatment plans and
      make appropriate decisions based on the volumetric images acquired at treatment.

PMID- 22483677
TI  - Performance and touch characteristics of disabled and non-disabled participants
      during a reciprocal tapping task using touch screen technology.
AB  - Touch screens are becoming more prevalent in everyday environments. Therefore, it
      is important that this technology is accessible to those with varying
      disabilities. The objective of the current study was to evaluate performance and
      touch characteristics (forces, impulses, and dwell times) of individuals with and
      without a movement disorder during a reciprocal tapping touch screen task. Thirty
      seven participants with a motor control disability and 15 non-disabled
      participants participated. Outcome measures include number of correct taps, dwell
      time, exerted force, and impulse. Results indicate non-disabled participants had
      1.8 more taps than participants with fine motor control disabilities and 2.8
      times more than those with gross motor impairments (p<0.05). Additionally, people
      with gross motor control disabilities demonstrated longer dwell times and greater
      impulses (p<0.05). The average force used to activate the buttons was 6.2 N,
      although the button activation force was 0.98 N. Differences in reciprocal
      tapping and touch characteristics exist between those with and without motor
      control disabilities. Understanding how people (including those with
      disabilities) interact with touch screens may allow designers and engineers to
      ultimately improve usability of touch screen technology.

PMID- 22483678
TI  - Profiling the multidimensional needs of new nursing home residents: evidence to
      support planning.
AB  - INTRODUCTION: Nursing home (NH) residents have various needs that affect the care
      they require. This article describes the diverse needs that new NH residents
      have, emphasizing the proportion of people with milder needs in multiple areas.
      METHODS: Research was conducted on all older adults newly admitted to not-for
      profit NHs in the Winnipeg Health Region, between April 1, 2005, and March 31,
      2007, provided that they were assessed using the Resident Assessment Instrument
      Minimum Data Set (RAI/MDS 2.0) within 30 days of admission (n = 1061). Using the
      Activities of Daily Living (ADL) Hierarchy scale, residents were first defined as
      low, intermediate, or high ADL dependent. Residents' needs were also defined
      using the RAI/MDS 2.0 cognitive performance (CPS) and pain scales, by their
      degree of behavioral problems and visual challenges, and by their frequency of
      bladder and bowel incontinence. Cluster analysis was used to create subgroups of
      residents by their severity of clinical challenges. RESULTS: Of our cohort, 26.8%
      were low ADL dependent. Although some of these residents had moderate to severe
      needs in another area, many (46.8% of low ADL-dependent residents; 12.5% of our
      entire cohort) had milder needs across all clinical domains. Conversely, about
      one-third of our cohort was high ADL dependent; 31.7% of these residents had
      moderate to severe challenges in one clinical domain, and 35.5% had moderate to
      severe comorbid challenges. CONCLUSIONS: Overall, 12.5% of our cohort had lower
      needs, demonstrating the capacity for community-based programs to offset NH
      demands. Also, the diversity of residents' needs highlights the importance of
      having both the appropriate resources and strategies available to provide quality
      NH care. Future research is discussed for both low- and higher-need NH residents.

PMID- 22483679
TI  - Analgesia targeting IB4-positive neurons in cancer-induced mechanical
      hypersensitivity.
AB  - Cancer patients often suffer from pain and most will be prescribed MU-opioids. MU
      opioids are not satisfactory in treating cancer pain and are associated with
      multiple debilitating side effects. Recent studies show that MU and delta opioid
      receptors are separately expressed on IB4 (-) and IB4 (+) neurons, which control
      thermal and mechanical pain, respectively. In this study we investigated IB4 (+)
      and IB4 (-) neurons in mechanical and thermal hypersensitivity in an orthotopic
      mouse oral cancer model. We used a delta opioid receptor agonist and a P2X(3)
      antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a
      key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia.
      Moreover, selective removal of IB4 (+) neurons using IB4-saporin impacts cancer
      induced mechanical but not thermal hypersensitivity. Our results demonstrate that
      peripherally administered pharmacological agents targeting IB4 (+) neurons, such
      as a selective delta-opioid receptor agonist or P2X(3) antagonist, might be
      useful in treating oral cancer pain. PERSPECTIVE: To clarify the mechanisms of
      oral cancer pain, we examined the differential role of IB4 (+) and IB4 (-)
      neurons. Characterization of these 2 subsets of putative nociceptors is important
      for further development of effective clinical cancer pain relief.

PMID- 22483680
TI  - Nabiximols for opioid-treated cancer patients with poorly-controlled chronic
      pain: a randomized, placebo-controlled, graded-dose trial.
AB  - Patients with advanced cancer who have pain that responds poorly to opioid
      therapy pose a clinical challenge. Nabiximols (Nabiximols is the U.S. Adopted
      Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, U.K.], which does not yet have
      an INN), a novel cannabinoid formulation, is undergoing investigation as add-on
      therapy for this population. In a randomized, double-blind, placebo-controlled,
      graded-dose study, patients with advanced cancer and opioid-refractory pain
      received placebo or nabiximols at a low dose (1-4 sprays/day), medium dose (6-10
      sprays/day), or high dose (11-16 sprays/day). Average pain, worst pain and sleep
      disruption were measured daily during 5 weeks of treatment; other questionnaires
      measured quality of life and mood. A total of 360 patients were randomized; 263
      completed. There were no baseline differences across groups. The 30% responder
      rate primary analysis was not significant for nabiximols versus placebo (overall
      P = .59). A secondary continuous responder analysis of average daily pain from
      baseline to end of study demonstrated that the proportion of patients reporting
      analgesia was greater for nabiximols than placebo overall (P = .035), and
      specifically in the low-dose (P = .008) and medium-dose (P = .039) groups. In the
      low-dose group, results were similar for mean average pain (P = .006), mean worst
      pain (P = .011), and mean sleep disruption (P = .003). Other questionnaires
      showed no significant group differences. Adverse events were dose-related and
      only the high-dose group compared unfavorably with placebo. This study supports
      the efficacy and safety of nabiximols at the 2 lower-dose levels and provides
      important dose information for future trials. PERSPECTIVE: Nabiximols, a novel
      cannabinoid formulation, may be a useful add-on analgesic for patients with
      opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled,
      graded-dose study demonstrated efficacy and safety at low and medium doses.

PMID- 22483682
TI  - Stepping out of history: mindfulness improves insight problem solving.
AB  - Insight problem solving is hindered by automated verbal-conceptual processes.
      Because mindfulness meditation training aims at "nonconceptual awareness" which
      involves a reduced influence of habitual verbal-conceptual processes on the
      interpretation of ongoing experience, mindfulness may facilitate insight problem
      solving. This hypothesis was examined across two studies (total N=157).
      Participants in both studies completed a measure of trait mindfulness and a
      series of insight and noninsight problems. Further, participants in Study 2
      completed measures of positive affect and a mindfulness or control training. The
      results indicated that (a) trait mindfulness predicts better insight but not
      noninsight problem solving (both studies), (b) this relation is maintained when
      controlling for positive affect (Study 2), (c) mindfulness training improves
      insight but not noninsight problem solving (Study 2) and (d) this improvement is
      partially mediated by state mindfulness (Study 2). These findings are the first
      to document a direct relation between mindfulness and creativity.

PMID- 22483681
TI  - Electric field depth-focality tradeoff in transcranial magnetic stimulation:
      simulation comparison of 50 coil designs.
AB  - BACKGROUND: Various transcranial magnetic stimulation (TMS) coil designs are
      available or have been proposed. However, key coil characteristics such as
      electric field focality and attenuation in depth have not been adequately
      compared. Knowledge of the coil focality and depth characteristics can help TMS
      researchers and clinicians with coil selection and interpretation of TMS studies.
      OBJECTIVE: To quantify the electric field focality and depth of penetration of
      various TMS coils. METHODS: The electric field distributions induced by 50 TMS
      coils were simulated in a spherical human head model using the finite element
      method. For each coil design, we quantified the electric field penetration by the
      half-value depth, d(1/2), and focality by the tangential spread, S(1/2), defined
      as the half-value volume (V(1/2)) divided by the half-value depth, S(1/2) =
      V(1/2)/d(1/2). RESULTS: The 50 TMS coils exhibit a wide range of electric field
      focality and depth, but all followed a depth-focality tradeoff: coils with larger
      half-value depth cannot be as focal as more superficial coils. The ranges of
      achievable d(1/2) are similar between coils producing circular and figure-8
      electric field patterns, ranging 1.0-3.5 cm and 0.9-3.4 cm, respectively.
      However, figure-8 field coils are more focal, having S(1/2) as low as 5 cm(2)
      compared to 34 cm(2) for circular field coils. CONCLUSIONS: For any coil design,
      the ability to directly stimulate deeper brain structures is obtained at the
      expense of inducing wider electrical field spread. Novel coil designs should be
      benchmarked against comparison coils with consistent metrics such as d(1/2) and
      S(1/2).

PMID- 22483683
TI  - A C-terminal interdomain disulfide bond significantly stabilizes the Fc fragment
      of IgG.
AB  - We describe the stabilization of human IgG1 Fc by an engineered interdomain
      disulfide bond at the C-terminal end of the molecule. Covalently interconnecting
      the C-termini of the CH(3) domains led to an increase of the melting temperatures
      by 5.6 and 9.1  degrees C respectively as compared to CH(3) domains in the
      context of the wild-type Fc. Combined with a recently described additional
      intradomain disulfide bond, both novel disulfide bonds led to an increase of the
      Tm by about 18.1  degrees C to 100.7  degrees C. The interdomain disulfide bond
      had no impact on the thermal stability of the CH(2) domain. Far- and near-UV CD
      spectroscopy showed very similar overall CD profiles, indicating that secondary
      and tertiary structure of the Fc was not negatively affected. When introduced
      into an Fc fragment that had been engineered to bind to Her2/neu via a novel
      antigen binding site located at the C-terminus of the CH(3) domain, the novel
      inter- and intra-domain bonds also brought about a significant increase in
      thermostability. Using them in combination, the Tm of the CH(3) domain was raised
      by 18  degrees C and thus restored to the Tm of the wild-type CH(3) domain.
      Importantly, antigen binding of the modified Fc was not affected by the
      engineered disulfide bonds.

PMID- 22483684
TI  - Metabolomic analysis to discover candidate therapeutic agents against acute
      pancreatitis.
AB  - Novel and effective drugs against acute pancreatitis are required. Therefore, we
      examined the changes in the metabolite levels in the serum and pancreatic tissue
      of mice with cerulein- and arginine-induced pancreatitis using gas
      chromatography/mass-spectrometry (GC/MS) and investigated whether these
      alterations affected the severity of acute pancreatitis. In the cerulein-induced
      pancreatitis model, 93 and 129 metabolites were detected in the serum and
      pancreatic tissue, respectively. In the L-arginine-induced acute pancreatitis
      model, 120 and 133 metabolites were detected in the serum and pancreatic tissue,
      respectively. Among the metabolites, the concentrations of tricarboxylic acid
      (TCA) cycle intermediates and amino acids were altered in pancreatitis, and in
      pancreatic tissue, the levels of the intermediates involved in the initial part
      of the TCA cycle were increased and those of the intermediates involved in the
      latter part of the TCA cycle were decreased. Some metabolites exhibited similar
      changes in both pancreatitis mouse models, e.g., the levels of glutamic acid and
      O-phosphoethanolamine were significantly decreased in the pancreatic tissue.
      Supplementation with glutamic acid and O-phosphoethanolamine attenuated the
      severity of cerulein-induced acute pancreatitis. Our results suggest that GC/MS
      based metabolomics is capable of accurately representing the status of acute
      pancreatitis, leading to the discovery of therapeutic agents for pancreatitis.

PMID- 22483685
TI  - Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility
      to intestinal Behcet's disease in Korean population.
AB  - AIMS: Although polymorphisms in IL23R have recently been proposed to predispose
      to Behcet's disease (BD), associations between IL23R polymorphisms and intestinal
      BD have yet to be elucidated. We therefore performed a study to evaluate whether
      IL17A, IL23R, and STAT4 polymorphisms are associated with susceptibility to
      intestinal BD in the Korean population. MAIN METHODS: Single nucleotide
      polymorphisms (SNP) in the IL17A, IL23R, and STAT4 genes were analyzed using DNA
      sequencing, denaturing high performance liquid chromatography, and TaqMan
      genotyping assays. KEY FINDINGS: Individual polymorphism analysis revealed that
      the TT genotype of IL17A rs8193036 (odds ratio (OR) 2.10, 95% confidence interval
      (CI) (1.12-3.92), p=0.021), and GG+GT genotype of IL23R rs1884444 (OR 1.92, 95%
      CI (1.03-3.57), p=0.034) was associated with the development of intestinal BD.
      When these two genotypes were combined, the risk of BD increased compared to that
      of patients with no-risk or one-risk genotype (OR 2.21, 95% CI (1.13-4.34),
      p=0.021). Furthermore, statistically significant gene-gene interactions were
      observed between G149R in IL23R vs. rs11685878 in STAT4, rs2275913 in IL17A vs.
      rs7574865 in STAT4, and rs11889341 in STAT4 vs. rs2275913 in IL17A. The
      haplotypes of IL17A had a positive association with intestinal BD risks, whereas
      those of IL23R were protective for disease development. SIGNIFICANCE: Our results
      indicate that the interaction of specific IL17A, IL23R, and STAT4 SNPs modulate
      susceptibility to intestinal BD in the Korean population, suggesting that the IL
      17/23 axis plays a significant role in disease pathogenesis.

PMID- 22483686
TI  - The putative somatostatin antagonist cyclo-somatostatin has opioid agonist
      effects in gastrointestinal preparations.
AB  - AIMS: Specificity of receptor antagonists used is crucial for clarifying
      physiological/pathophysiological roles of the respective endogenous agonist. We
      studied the effects (somatostatin antagonist and possibly other actions) of cyclo
      somatostatin (CSST), a putative somatostatin receptor antagonist on the guinea
      pig small intestine, a preparation where somatostatin causes inhibition of nerve
      mediated contractions. MAIN METHODS: In isolated organ experiments, half-maximal
      cholinergic "twitch" contractions of the guinea-pig small intestine were evoked
      or tonic contractions of the rat stomach fundus strip (in the presence of
      physostigmine) were elicited by electrical field stimulation. The effects of
      somatostatin (somatostatin-14), CSST, naloxone, as well as of direct smooth
      muscle stimulants were examined. KEY FINDINGS: Somatostatin (10 nM-1 MUM) caused
      transient inhibition of the twitch contraction, in a naloxone-insensitive manner.
      Surprisingly, CSST (0.3-1 MUM) also inhibited twitch contractions (more than 50%
      reduction at 1 MUM). This effect was prevented by the opioid receptor antagonist
      naloxone. Responses to acetylcholine or histamine were not or only minimally
      inhibited by CSST (up to 3 MUM). CSST (0.3 MUM in the absence or 1-10 MUM in the
      presence of naloxone) failed to inhibit the effect of somatostatin. The SST(2)
      receptor antagonist CYN-154806 (3 MUM) attenuated the effect of somatostatin and
      failed to evoke naloxone-sensitive inhibition of the twitch response. The
      naloxone-sensitive inhibitory effect of CSST on cholinergic contractions was also
      confirmed in the rat stomach fundus preparation. SIGNIFICANCE: Cyclo-somatostatin
      exerts opioid agonist activity in the two preparations tested, while it does not
      behave as a somatostatin-receptor antagonist in the guinea-pig intestine.

PMID- 22483687
TI  - Endothelin-1 induces itch and pain in the mouse cheek model.
AB  - AIMS: To date, suggestions that endothelin-1 (ET-1) causes nociception and
      pruritus are based on results in preclinical models in which responses to
      pruritic and nociceptive stimuli cannot be distinguished. This study reexamines
      these sensory effects of ET-1 in the new mouse cheek model, in which pruritogens
      and algogens evoke distinct behavioral responses. MAIN METHODS: Mice received
      intradermal (i.d.) injections of test substances into the left cheek and bouts of
      hind limb scratches or forepaw wipes, directed to the injection site, were
      considered indicative of pruritus and nociception, respectively. KEY FINDINGS:
      Histamine and capsaicin selectively evoked scratching and wipes, respectively,
      whereas ET-1 (3-60 pmol) promoted dose-dependent bouts of both behaviors. While
      scratching and wipe responses to ET-1 (30 pmol) were potentiated by BQ-788 (an
      ET(B) receptor antagonist) and reduced by co-injection of BQ-788 plus BQ-123 (an
      ET(A) receptor antagonist), BQ-123 alone inhibited scratching responses only.
      CTOP (MU-opioid receptor selective antagonist) only augmented scratching
      responses to ET-1, whereas DAMGO (MU-opioid receptor selective agonist) reduced
      both behaviors. Loratadine (histamine H(1) receptor antagonist) marginally
      reduced scratching, but markedly suppressed wipes. SIGNIFICANCE: These results
      demonstrate that ET-1 evokes pruritic and nociceptive behaviors in the mouse
      cheek model. Both responses to ET-1 appear to be mediated via ET(A) receptors and
      subjected to limitation by simultaneous ET(B) receptor activation. Local
      endogenous opioids acting on MU-opioid receptors selectively modulate the
      pruritic response to ET-1, whereas histamine, possibly derived from mast cells
      and acting on H(1) receptors, contributes importantly to the nociceptive effect
      of ET-1 in this model.

PMID- 22483688
TI  - New perspectives on endothelin-1 in atherosclerosis and diabetes mellitus.
AB  - Endothelin-1 (ET-1) is a vasoconstrictor, proinflammatory and proliferative
      endothelial cell-derived peptide that is of significant importance in the
      regulation of vascular function. It is involved in the development of endothelial
      dysfunction including important interactions with nitric oxide. The expression
      and functional effects of ET-1 and its receptors are markedly altered during
      development of cardiovascular disease. Increased production of ET-1 and its
      receptors mediate many pathophysiological events contributing to the development
      of atherosclerosis and vascular complications in diabetes mellitus. The present
      review focuses on the pathophysiological role of ET-1 and the potential
      importance of ET receptors as a therapeutic target for treatment of these
      conditions.

PMID- 22483689
TI  - Endothelin-1 enhances beta2-adrenoceptor gene transcription in human lung
      fibroblasts.
AB  - AIMS: The present study aimed to explore possible effects of endothelin-1 (ET-1)
      on beta(2)-adrenoceptor gene transcription in human lung fibroblasts. MAIN
      METHODS: MRC-5 human lung fibroblasts were cultured in absence or presence of
      test substances, followed by beta(2)-adrenoceptor mRNA determination by
      quantitative real time PCR. KEY FINDINGS: ET-1 caused a marked and rapid in onset
      (1 hr) increase in beta(2)-adrenoceptor mRNA, an effect additive to that of short
      time (1 hr) exposure to the beta(2)-adrenoceptor agonist olodaterol. The
      stimulatory effect of ET-1 on beta(2)-adrenoceptor mRNA was prevented by the non
      selective ET-A/ET-B receptor antagonist bosentan, indicating that it was mediated
      via specific ET receptors. In the presence of actinomycin D the effect of ET-1
      was prevented indicating that ET-1 acts via increased transcription of the
      beta(2)-adrenoceptor gene. ET-1-induced up-regulation of beta(2)-adrenoceptor
      mRNA was also seen in the presence of cycloheximide excluding indirect effects
      via up-regulation of other regulatory proteins. CONCLUSIONS: ET-1 can up-regulate
      beta-adrenoceptor gene transcription in human lung fibroblasts.

PMID- 22483690
TI  - Ameliorative potential of montelukast on ischemia-reperfusion injury induced
      vasculitic neuropathic pain in rat.
AB  - AIMS: Ischemia-reperfusion (I/R) event in vascular and nervous system has been
      documented to rising ischemic and vasculitic neuropathic pain, clinically
      resembles the complex regional pain syndrome (CRPS). The present study evaluated
      the effect of montelukast, a cysteinyl leukotriene receptor (Cys-LTC(4) and Cys
      LTD(4)) antagonist on ischemia -reperfusion (I/R) induced vasculitic neuropathic
      pain in rats. MAIN METHODS: Behavioral parameters were assessed at different time
      intervals (i.e. 0, 1, 7, 14 and 21st day) and biochemical analysis in sciatic
      nerve tissue samples were also performed along with histopathological studies.
      KEY FINDINGS: Behavioral pain assessment has shown increase in paw and tail
      withdrawal threshold in montelukast treated groups against thermal and mechanical
      stimuli as compared to I/R control group. We observed a decrease in the total
      calcium, thiobarbituric acid reactive substance (TBARS) and myeloperoxidase (MPO)
      activity levels, whereas there is rise in reduced glutathione level in
      montelukast treated groups as compared to I/R control group. However, significant
      behavioral and biochemical results were observed only in medium and high dose of
      treated groups which were comparable to normal control group. Moreover,
      histopathological study has revealed the reduction of I/R induced neuronal edema
      and axonal degeneration due to montelukast. SIGNIFICANCE: Montelukast has
      ameliorated I/R induced vasculitic neuropathic pain, these effects may be due to
      inhibition of lipid peroxidation, reduction of oxidative stress, release of
      inflammatory mediators and neuroprotective actions. Hence, it could be used as a
      novel therapeutic agent for the management of vasculitic inflammation related
      neuropathic pain.

PMID- 22483691
TI  - Presence of ChAT mRNA and a very marked alpha7nAChR immunoreaction in the
      synovial lining layer of the knee joint.
AB  - AIMS: The aim was to examine if there is evidence of acetylcholine (ACh)
      production within the synovial lining layer and to examine the pattern of
      alpha7nAChR expression in the layer. This layer is of relevance clinically as it
      becomes thickened in response to both rheumatoid arthritis (RA) and
      osteoarthritis (OA) and as it has been shown to produce proteases that are
      involved in the cartilage destruction. MAIN METHODS: Synovial tissue specimens
      from the knee joint of patients with RA and OA undergoing prosthetic surgery were
      examined. In situ hybridization and immunohistochemistry were used for the
      evaluation of ChAT reaction patterns. Immunohistochemistry was utilized for
      demonstration of activity of alpha7nAChR. KEY FINDINGS: There were ChAT mRNA
      reactions in the synovial lining layer of both patient categories. On the other
      hand, no ChAT immunoreactions were detected in the layer. There was a very marked
      alpha7nAChR immunoreaction. SIGNIFICANCE: There is a potential for ACh production
      within the synovial lining layer as there are ChAT mRNA reactions. However, the
      level of ACh production is apparently very low. It is thus possible that there is
      a down-regulation of ACh production but an apparent upregulation in expression
      level of alpha7nAChR. Based on the knowledge that the non-neuronal cholinergic
      system can have anti-inflammatory effects, the low level of ACh production in the
      synovial lining layer can be a drawback for the arthritic joints.

PMID- 22483692
TI  - Endothelin-1 increases superoxide production in human coronary artery bypass
      grafts.
AB  - AIMS: Endothelin-1 (ET-1) has been shown to increase endothelial superoxide
      (O(2)(-)) production in experimental animal models. It is unclear whether ET-1
      increases O(2)(-) production in humans. We sought to elucidate whether ET-1
      increases O(2)(-) production in human vessels and to identify the mechanism
      behind this effect. MAIN METHODS: Segments of internal mammary artery (IMA) and
      human saphenous vein (HSV) were harvested from 90 patients undergoing elective
      coronary artery bypass graft surgery. Paired vessel rings were incubated in the
      presence and absence of ET-1 (10(-10)M), the ET(A) receptor antagonist BQ123
      alone, or in combination with the ET(B) receptor antagonist BQ788 (dual BQ) and
      known inhibitors of sources of O(2)(-) and further analysed for O(2)(-)
      production using lucigenin-enhanced chemiluminescence and DHE fluorescence. KEY
      FINDINGS: ET-1 increased O(2)(-) production in both IMA (2.6 +/- 1.5 vs. 1.4 +/-
      0.8 relative light units/s/mg tissue (RLU); n=33; p < 0.0001) and HSV (1.4 +/-
      0.8 vs. 1.1 +/- 0.6 RLU; n=24; p<0.05). The increase in O(2)(-)production induced
      by ET-1 in IMA was inhibited by co-incubation with dual BQ (p < 0.05; n=15) and
      BQ123 (p<0.05; n = 17). Of known O(2)(-) inhibitors, only incubation with Tiron
      and diphenyleneiodonium resulted in a significant reduction in ET-mediated O(2)(
      ) production. SIGNIFICANCE: ET-1 increases O(2)(-) production especially in human
      arteries and less so in veins from patients with coronary artery disease via a
      receptor-dependent pathway involving a flavin dependent enzyme which is likely to
      be NADPH oxidase. Production of O(2)(-) may be an important factor underlying the
      negative effects of ET-1 on vascular function such as impairment of endothelium
      dependent vasodilatation and pro-inflammatory effects.

PMID- 22483693
TI  - Involvement of nicotinic acetylcholine receptor in the proliferation of mouse
      induced pluripotent stem cells.
AB  - AIMS: As the clinical use of induced pluripotent stem (iPS) cells may have the
      potential to overcome current obstacles in stem cell-based therapy, the molecular
      mechanisms that regulate the proliferation of iPS cells are of great interest.
      However, to our knowledge, no previous studies have examined whether stimulation
      with nicotinic acetylcholine receptor (nAchR) enhances the growth of iPS cells.
      In the present study, we examined the involvement of nAchR in the proliferation
      of mouse iPS cells. MAIN METHODS: We performed immunofluorescence staining to
      determine whether mouse iPS cells could express nAchRs. Mouse iPS cells were
      treated with nicotine for 24h under feeder-free conditions in the presence of
      leukemia inhibitory factor (LIF). The DNA synthesis was examined by the BrdU
      incorporation assay. Intracellular calcium levels were measured using Fluo-4
      acetoxymethyl (a cell-permeable calcium indicator). In addition, we examined the
      involvement of the CaMKP pathway in nicotine-enhanced proliferation of mouse iPS
      cells. KEY FINDINGS: The fluorescence images revealed that alpha(4)-nAchR and
      alpha(7)-nAchR are expressed on mouse iPS cells. Treatment of the cells with
      300nM nicotine significantly increases DNA synthesis. This is significantly
      inhibited by pretreatment with antagonists of alpha(4)-nAchR and alpha(7)-nAchR
      or a CaMKP inhibitor. In addition, treatment with nicotine increases the
      intracellular Ca(2+) level dose-dependently in mouse iPS cells. Treatment with
      nicotine significantly enhances CaMKP phosphorylation. SIGNIFICANCE: The present
      study indicates that stimulation of alpha(4)-nAchR and alpha(7)-nAchR may lead to
      a significant increase in the rate of mouse iPS cell proliferation through
      enhancement of the CaMKP signaling pathway.

PMID- 22483694
TI  - Role of CD69 in acute lung injury.
AB  - AIMS: CD69 is an early activation marker in lymphocytes and an important signal
      transmitter in inflammatory processes. However, its role in acute lung injury
      (ALI) is still unknown. We used a lipopolysaccharide (LPS)-induced mouse model of
      ALI to study the role of macrophage-surface CD69 in this condition. MAIN METHODS:
      We investigated bronchoalveolar lavage fluid (BALF) cell subpopulations,
      myeloperoxidase levels in lung homogenates, lung pathology, and lung oedema in
      CD69-deficient (CD69(-/-)) mice 24h after LPS instillation. We also determined
      cytokine/chemokine expression levels in BALF and macrophage culture supernatant
      from CD69(-/-) and wild type (WT) mice. Also, we investigated CD69, keratinocyte
      derived chemokine (KC) and macrophage inflammatory protein (MIP)-2 localization
      in the lungs after LPS administration. Furthermore, we examined the effect of
      anti-CD69 antibody on LPS-induced cytokine/chemokine release from cultured
      macrophages. KEY FINDINGS: Our study shows that intratracheal instillation of LPS
      induced neutrophilic infiltration, histopathological changes, myeloperoxidase
      positivity, and oedema in the lung to a lower degree in CD69(-/-) mice than in WT
      mice. The immunoreactivities for CD69, KC and MIP2 were induced in the lung of WT
      mice instilled with LPS and were predominantly localized to the macrophages.
      Moreover, the cytokine/chemokine expression profile between the two genotypes of
      cultured macrophages in response to LPS was similar to that observed in the BALF.
      In addition, anti-CD69 antibody inhibited the LPS-induced cytokine/chemokine
      expression. SIGNIFICANCE: These results suggest that CD69 on macrophages plays a
      crucial role in the progression of LPS-induced ALI and may be a potentially
      useful target in the therapy for ALI.

PMID- 22483695
TI  - Hyperthermic seizures enhance responsiveness to pentylenetetrazole and induce
      cognitive dysfunction: protective effect of 3-alkynyl selenophene.
AB  - AIMS: In this study we investigated the effect of pre-treatment with 3-alkynyl
      selenophene (3-ASP) against the increase in responsiveness to pentylenetetrazole
      [PTZ seizure threshold] and cognitive dysfunction induced by experimental febrile
      seizures (FS). The effects of 3-ASP were compared to those of diazepam (DZP).
      MAIN METHODS: Young rats, at postnatal day 21, developed seizures after exposure
      to a stream of heated air to approximately 41 degrees C. A non-spatial long-term
      memory and PTZ seizure threshold were determined 30 days after FS. The
      behavioural seizures were stereotyped followed by facial automatisms, often
      followed by body flexion. Young rats were pre-treated with 3-ASP (50 and
      100mg/kg; per oral route), DZP (1 and 5mg/kg; intraperitoneally) or vehicle. KEY
      FINDINGS: 3-ASP and DZP pre-treatments were not effective in protecting against
      seizures induced by FS. 3-ASP pre-treatment protected against the increase in
      responsiveness to PTZ and cognitive dysfunction induced by FS. DZP pre-treatment
      was effective in protecting against the increase in responsiveness to PTZ, but
      not, against the impaired memory induced by FS. SIGNIFICANCE: 3-ASP pre-treatment
      protected against impairment of memory performance in the step-down passive
      avoidance task and the increase in the susceptibility to seizures caused by FS
      early in life of rats.

PMID- 22483696
TI  - Predicting the probability of abnormal stimulated growth hormone response in
      children after radiotherapy for brain tumors.
AB  - PURPOSE: To develop a mathematical model utilizing more readily available
      measures than stimulation tests that identifies brain tumor survivors with high
      likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid
      late recognition and a consequent delay in growth hormone replacement therapy.
      METHODS AND MATERIALS: We analyzed 191 prospectively collected post-RT
      evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation
      test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height,
      weight, growth velocity, and body mass index in 106 children and adolescents
      treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma
      (n=6), who had normal growth hormone levels before RT. Normal level in this study
      was defined as the peak growth hormone response to the stimulation test>=7 ng/mL.
      RESULTS: Independent predictor variables identified by multivariate logistic
      regression with high statistical significance (p<0.0001) included IGF-1 z score,
      weight z score, and hypothalamic dose. The developed predictive model
      demonstrated a strong discriminatory power with an area under the receiver
      operating characteristic curve of 0.883. At a potential cutoff point of
      probability of 0.3 the sensitivity was 80% and specificity 78%. CONCLUSIONS:
      Without unpleasant and expensive frequent stimulation tests, our model provides a
      quantitative approach to closely follow the growth hormone secretory capacity of
      brain tumor survivors. It allows identification of high-risk children for
      subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone
      deficiency.

PMID- 22483697
TI  - Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation
      Therapy Oncology Group consensus panel atlas.
AB  - PURPOSE: To define a male and female pelvic normal tissue contouring atlas for
      Radiation Therapy Oncology Group (RTOG) trials. METHODS AND MATERIALS: One male
      pelvis computed tomography (CT) data set and one female pelvis CT data set were
      shared via the Image-Guided Therapy QA Center. A total of 16 radiation
      oncologists participated. The following organs at risk were contoured in both CT
      sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions),
      bowel NOS (not otherwise specified), small bowel, large bowel, and proximal
      femurs. The following were contoured in the male set only: bladder, prostate,
      seminal vesicles, and penile bulb. The following were contoured in the female set
      only: uterus, cervix, and ovaries. A computer program used the binomial
      distribution to generate 95% group consensus contours. These contours and
      definitions were then reviewed by the group and modified. RESULTS: The panel
      achieved consensus definitions for pelvic normal tissue contouring in RTOG trials
      with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag,
      Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb,
      Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve
      as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum.
      Detailed target volume contouring guidelines and images are discussed.
      CONCLUSIONS: Consensus guidelines for pelvic normal tissue contouring were
      reached and are available as a CT image atlas on the RTOG Web site. This will
      allow uniformity in defining normal tissues for clinical trials delivering pelvic
      radiation and will facilitate future normal tissue complication research.

PMID- 22483698
TI  - Mapping of RBE-weighted doses between HIMAC- and LEM-Based treatment planning
      systems for carbon ion therapy.
AB  - PURPOSE: A method was developed to convert clinically prescribed RBE (Relative
      Biological Effectiveness)-weighted doses from the approach used at the Heavy-Ion
      Medical Accelerator (HIMAC) at the National Institute of Radiological Science,
      Chiba, Japan, to the LEM (Local Effect Model)-based TReatment planning for
      Particles (TRiP98) approach used in the pilot project at the GSI
      Helmholtzzentrum, Darmstadt, and the Heidelberg Ion-Beam Therapy Center (HIT).
      METHODS AND MATERIALS: The proposed conversion method is based on a simulation of
      the fixed spread-out Bragg peak (SOBP) depth dose profiles as used for the
      irradiation at HIMAC by LEM/TRiP98 and a recalculation of the resulting RBE
      weighted dose distribution. We present data according to the clinical studies
      conducted at GSI in the past decade (LEM I), as well as data used in current
      studies (refined LEM version: LEM IV). RESULTS: We found conversion factors (RBE
      weighted dose LEM/RBE-weighted dose HIMAC) reaching from 0.4 to 2.0 for
      prescribed carbon ion doses from 1 to 60 Gy (RBE) for SOBP extensions ranging
      from 20 to 120 mm according to the HIMAC approach. A conversion factor of 1.0 was
      found for approximately 5 Gy (RBE). The conversion factor decreases with
      increasing prescribed dose. Slightly smaller values for the LEM IV-based data set
      compared with LEM I were found. A significant dependence of the conversion factor
      from the SOBP width could be observed in particular for LEM IV, whereas the depth
      dependence was found to be small. CONCLUSIONS: For the interpretation and
      comparison of clinical trials performed at HIMAC and GSI/HIT, it is of extreme
      importance to consider these conversion factors because according to the various
      methods to determine the RBE-weighted dose, similar dose values might not
      necessarily be related to similar clinical outcomes.

PMID- 22483699
TI  - The dosimetric effect of intrafraction prostate motion on step-and-shoot
      intensity-modulated radiation therapy plans: magnitude, correlation with motion
      parameters, and comparison with helical tomotherapy plans.
AB  - PURPOSE: To determine the daily and cumulative dosimetric effects of
      intrafraction prostate motion on step-and-shoot (SNS) intensity-modulated
      radiation therapy (IMRT) plans, to evaluate the correlation of dosimetric effect
      with motion-based metrics, and to compare on a fraction-by-fraction basis the
      dosimetric effect induced in SNS and helical tomotherapy plans. METHODS AND
      MATERIALS: Intrafraction prostate motion data from 486 fractions and 15 patients
      were available. A motion-encoded dose calculation technique was used to determine
      the variation of the clinical target volume (CTV) D(95%) values with respect to
      the static plan for SNS plans. The motion data were analyzed separately, and the
      correlation coefficients between various motion-based metrics and the dosimetric
      effect were determined. The dosimetric impact was compared with that incurred
      during another IMRT technique to assess correlation across different delivery
      techniques. RESULTS: The mean (+/-1 standard deviation [SD]) change in D(95%) in
      the CTV over all 486 fractions was 0.2 +/- 0.5%. After the delivery of five and
      12 fractions, the mean (+/-1 SD) changes over the 15 patients in CTV D(95%) were
      0.0 +/- 0.2% and 0.1 +/- 0.2%, respectively. The correlation coefficients between
      the CTV D(95%) changes and the evaluated motion metrics were, in general, poor
      and ranged from r = -0.2 to r = -0.39. Dosimetric effects introduced by identical
      motion in SNS and helical tomotherapy IMRT techniques were poorly correlated with
      a correlation coefficient of r = 0.32 for the CTV. CONCLUSIONS: The dosimetric
      impact of intrafraction prostate motion on the CTV is, in general, small. In only
      4% of all fractions did the dosimetric consequence exceed 1% in the CTV. As
      expected, the cumulative effect was further reduced with fractionation. The poor
      correlations between the calculated motion parameters and the subsequent
      dosimetric effect implies that motion-based thresholds are of limited value in
      predicting the dosimetric impact of intrafraction motion. The dosimetric effects
      between the two evaluated delivery techniques were poorly correlated.

PMID- 22483700
TI  - Reproductive status at first diagnosis influences risk of radiation-induced
      second primary contralateral breast cancer in the WECARE study.
AB  - PURPOSE: Our study examined whether reproductive and hormonal factors before, at
      the time of, or after radiation treatment for a first primary breast cancer
      modify the risk of radiation-induced second primary breast cancer. METHODS AND
      MATERIALS: The Women's Environmental, Cancer and Radiation Epidemiology (WECARE)
      Study is a multicenter, population-based study of 708 women (cases) with
      asynchronous contralateral breast cancer (CBC) and 1399 women (controls) with
      unilateral breast cancer. Radiotherapy (RT) records, coupled with anthropomorphic
      phantom simulations, were used to estimate quadrant-specific radiation dose to
      the contralateral breast for each patient. Rate ratios (RR) and 95% confidence
      intervals (CI) were computed to assess the relationship between reproductive
      factors and risk of CBC. RESULTS: Women who were nulliparous at diagnosis and
      exposed to >=1 Gy to the contralateral breast had a greater risk for CBC than did
      matched unexposed nulliparous women (RR=2.2; 95% CI, 1.2-4.0). No increased risk
      was seen in RT-exposed parous women (RR=1.1; 95% CI, 0.8-1.4). Women treated with
      RT who later became pregnant (8 cases and 9 controls) had a greater risk for CBC
      (RR=6.0; 95% CI, 1.3-28.4) than unexposed women (4 cases and 7 controls) who also
      became pregnant. The association of radiation with risk of CBC did not vary by
      number of pregnancies, history of breastfeeding, or menopausal status at the time
      of first breast cancer diagnosis. CONCLUSION: Nulliparous women treated with RT
      were at an increased risk for CBC. Although based on small numbers, women who
      become pregnant after first diagnosis also seem to be at an increased risk for
      radiation-induced CBC.

PMID- 22483701
TI  - Treatment outcomes in non-metastatic prostate cancer patients with ultra-high
      prostate-specific antigen.
AB  - PURPOSE: It is commonly believed that prostate cancer patients with very high
      prostate-specific antigen (PSA) levels are unlikely to benefit from definitive
      local treatment, and patients with very high PSA are often underrepresented in,
      or excluded from, randomized clinical trials. Consequently, little is known about
      their optimal treatment or prognosis. We performed a registry-based analysis of
      management and outcome in this population of patients. METHODS AND MATERIALS: Our
      provincial Cancer Registry was used to identify all men who were diagnosed with
      prostate cancer from 1990 to 2001. A retrospective chart review provided
      information on stage, Gleason score, PSA at diagnosis, and treatment. In this
      study, ultra-high PSA was defined as PSA of >= 50 ng/ml. For a more complete
      perspective, treatment outcomes of patients with PSA of 20 to 49.9 ng/ml were
      also studied. RESULTS: Of the 8378 men diagnosed with prostate cancer during this
      period, 6,449 had no known nodal or distant metastatic disease. The median follow
      up of this group was 67.2 months (range, 0-192 months). A total of 1534 patients
      had PSA of >= 20 ng/ml. Among the 995 patients with PSA 20 to 49.9 ng/ml, 85 had
      radical prostatectomy (RP), and their 5- and 10-year cause-specific survivals
      (CSS) were 95% and 84%, respectively. The 497 patients treated with radiotherapy
      (RT) had 5- and 10-year CSS of 92% and 71%. For the 332 patients with PSA 50-99.9
      ng/ml, RT was associated with 5- and 10-year CSS of 81% and 55%. For the 207
      patients with PSA of >= 100 ng/ml, RT was associated with 5- and 10-year CSS of
      80% and 54%. CONCLUSIONS: This is the largest series in the world on non
      metastatic cancer patients with ultra-high PSA at diagnosis. Even in the setting
      of a very high presenting PSA level, prostatectomy and radiotherapy are often
      associated with prolonged survival.

PMID- 22483702
TI  - Targeting FAK radiosensitizes 3-dimensional grown human HNSCC cells through
      reduced Akt1 and MEK1/2 signaling.
AB  - PURPOSE: Focal adhesion kinase (FAK), a main regulator of integrin signaling and
      cell migration, is frequently overexpressed and hyperphosphorylated in human head
      and-neck squamous cell carcinoma (HNSCC). We have previously shown that
      pharmacologic FAK inhibition leads to radiosensitization of 3-dimensionally grown
      HNSCC cell lines. To further evaluate the role of FAK in radioresistance and as a
      potential cancer target, we examined FAK and FAK downstream signaling in HNSCC
      cell lines grown in more physiologic extracellular matrix-based 3-dimensional
      cell cultures. METHODS AND MATERIALS: Seven HNSCC cell lines were grown in 3
      dimensional extracellular matrix and the clonogenic radiation survival,
      expression, and phosphorylation of FAK, paxillin, Akt1, extracellular signal
      regulated kinase (ERK)1/2, and MEK1/2 were analyzed after siRNA-mediated
      knockdown of FAK, Akt1, MEK1, FAK+Akt1, or FAK+MEK1 compared with controls or
      stable overexpression of FAK. The role of MEK1/2 for clonogenic survival and
      signaling was investigated using the MEK inhibitor U0126 with or without
      irradiation. RESULTS: FAK knockdown moderately or significantly enhanced the
      cellular radiosensitivity of 3-dimensionally grown HNSCC cells. The FAK
      downstream targets paxillin, Akt1, and ERK1/2 were substantially dephosphorylated
      under FAK depletion. FAK overexpression, in contrast, increased radiation
      survival and paxillin, Akt1, and ERK1/2 phosphorylation. The degree of
      radiosensitization upon Akt1, ERK1/2, or MEK1 depletion or U0126 was
      superimposable to FAK knockdown. Combination knockdown conditions (ie, Akt1/FAK,
      MEK1/FAK, or U0126/FAK) failed to provide additional radiosensitization.
      CONCLUSIONS: Our data provide further evidence for FAK as important determinant
      of radiation survival, which acts in the same signaling axis as Akt1 and ERK1/2.
      These data strongly support our hypothesis that FAK is a relevant molecular
      target for HNSCC radiotherapy.

PMID- 22483703
TI  - Integrating radical local treatment of the primary in the management of stage IV
      breast cancer. When is the best moment for the resection of the primary tumor?

PMID- 22483704
TI  - Surgical complications and long-term survival after esophagectomy for cancer in a
      nationwide Swedish cohort study.
AB  - AIMS: Acute surgical complications after esophageal resection for cancer may
      decrease the long-term survival. Previous results on this topic are conflicting
      and no population-based studies are available. METHODS: A prospective, nationwide
      Swedish study was conducted in 2001-2010. Eligible patients comprised those
      afflicted by esophageal or cardia cancer and underwent surgical resection in
      Sweden in 2001-2005. Details concerning patient and tumor characteristics,
      surgical procedures, and postoperative surgical complications were collected
      prospectively. Follow-up for mortality, starting from 90 days after the surgery,
      was done until May 2010. Cox proportional-hazards regression was performed to
      estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for
      age, tumor stage, sex, histology, comorbidity, surgical approach and surgical
      radicality. RESULTS: Among 567 included patients who survived at least 90 days
      postoperatively, 130 (22.9%) sustained a predefined surgical complication within
      30 days of surgery. The adjusted HR of mortality was increased in patients who
      sustained surgical complications, compared to patients without such complications
      (HR 1.29, 95% CI 1.02-1.63). CONCLUSIONS: The occurrence of surgical
      complications might be an independent predictor for poorer long-term survival in
      patients resected for esophageal cancer, even in patients who survived the
      postoperative period.

PMID- 22483705
TI  - Psychotropics in pregnancy: safety and other considerations.
AB  - INTRODUCTION: Perinatal psychiatric disorders are important because of their
      adverse effects on pregnancy outcomes. The aim of this review is investigate
      psychotropic drugs in the management of antenatal psychiatric disorders with
      emphasis on the risk of harmful effects. METHOD: A systematic review of published
      electronic literature between January 2000 and August 2011 was conducted using
      the following keywords: pregnancy, pregnancy complications, neonatal
      complications, congenital anomalies, infant/child development, antidepressants,
      antipsychotics, and lithium. The search was conducted for each class of
      psychotropic agents. Further hand searches were conducted. Anticonvulsants were
      excluded. RESULTS: Antidepressants are associated with increased risk of
      spontaneous abortions, stillbirths, preterm deliveries, respiratory distress,
      endocrine and metabolic disturbance. There is evidence of discontinuation
      syndrome and of increased risk of cardiac defects. Antipsychotics are associated
      with increased gestational weight and diabetes and with increased risk of preterm
      birth. The effects of antipsychotics on birth weight are inconclusive. In
      addition, the findings in relation to malformations are inconclusive. Lithium is
      associated with increased birth complications such as polyhydramnios, pre
      eclampsia, respiratory distress syndrome, hypotonia, and preterm birth. Lithium
      has previously been associated with markedly increased risk of Ebstein's anomaly.
      However, recent re-evaluation of the data casts doubt on the previous estimates.
      There is evidence that lithium is associated with cardiac septal defects.
      CONCLUSION: Psychotropic drugs remain an important treatment option during
      pregnancy to properly manage symptoms of psychiatric diseases. Clinicians need to
      remain aware of the potential risk of adverse effects associated with
      psychotropic drug treatment.

PMID- 22483706
TI  - What impact does contact with the prenatal care system have on women's use of
      facility delivery? Evidence from low-income countries.
AB  - Prenatal and delivery care are critical both for maternal and newborn health.
      Using the Demographic and Health Surveys (DHS) data for thirty-two low-income
      countries across Asia, sub-Saharan Africa and Latin America, and employing a two
      level random-intercept model, this paper empirically assesses the influence of
      prenatal attendance and a wide array of observed individual-, household- and
      community-level characteristics on a woman's decision to give birth at a health
      facility or at home. The results show that prenatal attendance does appreciably
      influence the use of facility delivery in all three geographical regions, with
      women having four visits being 7.3 times more likely than those with no prenatal
      care to deliver at a health facility. These variations are more pronounced for
      Sub-Saharan Africa. The influence of the number of prenatal visits, maternal age
      and education, parity level, and economic status of the birthing women on the
      place of delivery is found to vary across the three geographical regions. The
      results also indicate that obstetrics care is geographically and economically
      more accessible to urban and rural women from the non-poor households than those
      from the poor households. The strong influence of number of visits, household
      wealth, education and regional poverty on the site of delivery setting suggests
      that policies aimed at increasing the use of obstetric care programs should be
      linked with the objectives of social development programs such as poverty
      reduction, enhancing the status of women, and increasing primary and secondary
      school enrollment rate among girls.

PMID- 22483708
TI  - Impact of war, religiosity and ideology on PTSD and psychiatric disorders in
      adolescents from Gaza Strip and South Lebanon.
AB  - This study investigated the extent to which differences in the types of war
      trauma, economic pressure, religiosity and ideology accounted for variation in
      PTSD and psychiatric disorders among adolescents from Gaza Strip and South
      Lebanon. Participants were 600 adolescents aged 12-16 years. They were selected
      from the public school system in the highly war exposed areas. Questionnaires
      were administered in an interview format with adolescents at school by two
      trained psychologists. Results indicated that the various types of trauma had
      differential effects on the psychological status of adolescents in both
      countries. Economic pressure was more predictive of PTSD and psychological
      distress in adolescents from Gaza. Differences in religiosity and ideology did
      not account for similar variation in stress response among adolescents from Gaza
      and South Lebanon. While higher levels of religiosity evidenced the greatest
      levels of depression and anxiety in adolescents from Gaza, religiosity had an
      attenuated effect on adolescents from South Lebanon. Ideology was negatively
      associated with depression and anxiety in Gaza strip adolescents, whereas it did
      not play a role for adolescents from South Lebanon. The clinical and research
      implications of these conclusions are discussed.

PMID- 22483707
TI  - Social relationships and inflammatory markers: an analysis of Taiwan and the U.S.
AB  - We evaluated the association between two aspects of social relationships and six
      inflammatory markers in Taiwan and the U.S. These two countries share similar
      levels of current life expectancy, but exhibit important differences in social
      structure. The data comprised population based samples from Taiwan (aged 53+;
      n=962) and the U.S. (aged 35-86; n=990) collected between 2003 and 2009.
      Circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen,
      and soluble forms of intercellular adhesion molecule 1, E-selectin, and IL-6
      receptor (sIL-6R) were measured in fasting blood samples. A social integration
      score was based on marital status, contact with family and friends, church
      attendance, and other social participation. A perceived social support index was
      based on questions regarding the availability of care and support from family and
      friends. Linear regression models tested the association between these two
      measures and each inflammatory marker controlling for sociodemographic
      characteristics, obesity, medication use, and baseline health status. After
      adjusting for potential confounders, social integration had a significant but
      weak inverse association with CRP in Taiwan. Perceived social support was
      significant in two of 12 models, and the coefficient was positive (i.e., higher
      support was associated with higher CRP and sIL-6R in the U.S.). We found no
      evidence that the coefficients for social relationship measures varied by sex or
      age. Our results yielded limited evidence of a weak association between two
      dimensions of social relationships and six inflammatory markers in Taiwan and the
      U.S. Given that the literature suggests a strong link between social
      relationships and mortality, and that inflammation plays an important role in the
      leading causes of death, we had expected to find consistent and moderately strong
      associations between social relationships and inflammatory markers. The small
      effect sizes and lack of robustness across markers were surprising.

PMID- 22483709
TI  - Are ciliated protozoa communities affected by macrophyte species, date of
      sampling and location in horizontal sub-surface flow constructed wetlands?
AB  - The effects of design and operational factors on the dynamics of ciliated
      protozoa in constructed wetlands (CWs) treating wastewater remain poorly known,
      although bacterivory by ciliates could have important implications for nutrient
      cycling in these systems. We conducted a greenhouse experiment with eight wetland
      mesocosms (1 m(2)) fed with synthetic wastewater to assess how macrophyte species
      (Phragmites australis, Phalaris arundinacea, and Typha angustifolia), location
      within CW (longitudinal, depth), and temporal fluctuations affect ciliate
      abundance and diversity. Urosoma similis was the most abundant taxon, but
      Hypotrichidae, Scuticociliates, Drepomonas revoluta, and Acineria uncinata were
      also abundant. Longitudinal location had the highest impact on ciliate dynamics,
      with more abundant and diverse communities in the initial section of wetlands. P.
      australis/T. angustifolia and P. arundinacea had the most and least favorable
      conditions for ciliates, respectively, but differences among macrophytes were
      mostly not significant. Ciliate abundance appeared to decline from August to
      November, most likely because of lower temperature and plant inputs of organic
      matter and oxygen. Depth had no apparent impact on ciliate dynamics, suggesting
      that sampling at multiple depths in CW is not necessary to adequately monitor
      ciliate communities. Overall, our results suggest that macrophytes, location, and
      date of sampling influenced ciliated dynamics but stress the need for direct
      manipulative experiments of ciliate abundance, diversity, and composition
      conducted on a full annual cycle to better understand the impact of ciliates on
      nutrient cycling in CWs. This is especially true to determine if the associations
      found in our principal component analysis are robust.

PMID- 22483710
TI  - Anchorage of iron hydro(oxide) nanoparticles onto activated carbon to remove
      As(V) from water.
AB  - The adsorption of arsenic (V) by granular iron hydro(oxides) has been proven to
      be a reliable technique. However, due to the low mechanical properties of this
      material, it is difficult to apply it in full scale water treatment. Hence, the
      aim of this research is to develop a methodology to anchor iron hydro(oxide)
      nanoparticles onto activated carbon, in which the iron hydro(oxide) nanoparticles
      will give the activated carbon an elevated active surface area for arsenic
      adsorption and also help avoid the blockage of the activated carbon pores. Three
      activated carbons were modified by employing the thermal hydrolysis of iron as
      the anchorage procedure. The effects of hydrolysis temperature (60-120  degrees
      C), hydrolysis time (4-16 h), and FeCl(3) concentration (0.4-3 mol Fe/L) were
      studied by the surface response methodology. The iron content of the modified
      samples ranged from 0.73 to 5.27%, with the higher end of the range pertaining to
      the carbons with high oxygen content. The materials containing smaller iron
      hydro(oxide) particles exhibited an enhanced arsenic adsorption capacity. The
      best adsorbent material reported an arsenic adsorption capacity of 4.56 mg As/g
      at 1.5 ppm As at equilibrium and pH 7.

PMID- 22483711
TI  - Clear model fluids to emulate the rheological properties of thickened digested
      sludge.
AB  - Optimising flow processes in wastewater treatment plants requires that designers
      and operators take into account the flow properties of the sludge. Moreover, due
      to increasingly more stringent conditions on final disposal avenues such as
      landfill, composting, incineration etc., practitioners need to produce safer
      sludge in smaller quantities. Anaerobic digestion is a key treatment process for
      solids treatment and pathogen reduction. Due to the inherent opacity of sludge,
      it is impossible to visualise the mixing and flow patterns inside an anaerobic
      digester. Therefore, choosing an appropriate transparent model fluid which can
      mimic the rheological behaviour of sludge is imperative for visualisation of the
      hydrodynamic functioning of an anaerobic digester. Digested sludge is a complex
      material with time dependent non-Newtonian thixotropic characteristics. In steady
      state, it can be modelled by a basic power-law. However, for short-time processes
      the Herschel-Bulkley model can be used to model liquid-like properties. The
      objective of this study was to identify transparent model fluids which will mimic
      the behaviour of real sludge. A comparison of three model fluids, Carboxymethyl
      Cellulose (CMC), Carbopol gel and Laponite clay revealed that these fluids could
      each model certain aspects of sludge behaviour. It is concluded that the
      rheological behaviour of sludge can be modelled using CMC in steady state flow at
      high shear rates, Carbopol gel for short-time flow processes and Laponite clay
      suspension where time dependence is dominant.

PMID- 22483712
TI  - Input characterization of perfluoroalkyl substances in wastewater treatment
      plants: source discrimination by exploratory data analysis.
AB  - This paper presents a methodology based on multivariate data analysis for
      identifying input sources of perfluoroalkyl substances (PFASs) detected in 37
      wastewater treatment plants (WWTPs) across more than 40 cities in the state of
      Minnesota (USA). Exploratory analysis of data points has been carried out by
      unsupervised pattern recognition (cluster analysis), correlation analysis, ANOVA
      and per capita discharges in an attempt to discriminate sources of PFASs in
      WWTPs. Robust cluster solutions grouped the database according to the different
      PFAS profiles in WWTP influent. Significantly elevated levels of
      perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) and/or
      perfluorooctane sulfonate (PFOS) in influent have been found in 18 out of 37
      WWTPs (49%). A substantial increase in the concentrations of PFHxA and/or PFOA
      from influent to effluent was observed in 59% of the WWTPs surveyed, suggestive
      of high concentration inputs of precursors. The fate of one precursor (8:2
      fluorotelomer alcohol) in WWTP was modeled based on fugacity analysis to
      understand the increasing effluent concentration. Furthermore, population-related
      emissions cannot wholly explain the occurrence and levels of PFASs in WWTPs.
      Unusually high influent levels of PFASs were observed in WWTPs located in
      specific industrial areas or where known contamination had taken place. Despite
      the restriction on the production/use of PFOA and PFOS, this paper demonstrates
      that wastewater from industrial activities is still a principal determinant of
      PFAS pollution in urban watersheds.

PMID- 22483713
TI  - Removal kinetic model of oil droplet from o/w emulsion by adding methylated milk
      casein in flotation.
AB  - In this study, o/w emulsion flotation experiments were conducted by adding
      methylated milk casein (MeSC). Emulsion used in this study was prepared by
      ultrasonic emulsification of heavy oil (bunker-A) and sodium dodecyl sulfate
      (SDS) solution. A simple kinetic model was proposed to estimate the removal rate
      of the oil droplets within the column. The model was based on main assumption
      that adsorption of single droplet adsorbed MeCS or floc onto bubble surface
      within flotation column. Removal rate constant, K, was defined by k(a)X(s)
      (S(b)tau/V), where k(a) and X(s) are overall adsorption rate and saturated
      adsorption density of oil droplet or floc, S(b), tau and V are bubble surface
      production rate, retention time of bubble swarms and emulsion volume within the
      column, respectively. The experiments were conducted with varying operating
      conditions; superficial gas velocity, column dimension and emulsion volume. K was
      evaluated from slope value of obtained straight line by plotting time versus ln
      (T/T(0)), where T/T(0) is relative turbidity. K was mostly proportional to
      (S(b)tau/V), which corresponds to specific surface area of bubble swarms per unit
      volume within the column, in the present experimental region. This result
      suggested that efficiency of this removal process was mainly controlled by the
      specific surface area of bubble swarms, and proposed model was fundamentally
      verified.

PMID- 22483714
TI  - Antioxidant activity of black currant (Ribes nigrum L.) extract and its
      inhibitory effect on lipid and protein oxidation of pork patties during chilled
      storage.
AB  - This experiment was conducted to assess the antioxidant efficacy of black currant
      (Ribes nigrum L.) extract (BCE) in raw pork patties during chilled storage. The
      extracting conditions of frozen BCE including ethanol concentrations (0-100%) and
      extracting times (0.25-12h) were studied. BCE extracted with 40% ethanol for 2h
      had the highest anthocyanin content, the strongest radical scavenging activities
      as well as the second strongest reducing power. BCE was condensed and added to
      pork patties at 5, 10 or 20 g/kg. Compared with the control, BCE treatments
      significantly decreased the thiobarbituric acid-reactive substance values and
      carbonyls formation and reduced the sulfhydryl loss of pork patties in a dose
      dependent manner (P<0.05), which showed that the BCE significantly inhibited
      lipid and protein oxidation. The BCE-treated patties showed significantly higher
      redness (P<0.05) than the control. The findings demonstrated strong potential for
      BCE as a natural antioxidant in meat and meat products.

PMID- 22483715
TI  - [Evolution of electrohysterogram signals synchronization according to term of
      pregnancy: interest for preterm labor diagnosis].
AB  - OBJECTIVES: Our study focuses on the analysis of the uterine electromyogram
      recorded on women during pregnancy. We were interested in evaluating the
      synchronization of this electrical signal at various terms in order to follow
      evolution of synchronization as labor approaches. This study attempts to deepen
      our understanding of the myometrial maturation close to labor and to provide
      reliable parameters for improving preterm labor diagnosis. PATIENTS AND METHODS:
      We performed a prospective study by recording the electrical signals of
      physiological uterine contractions (causing no delivery) on 16 pregnant women. We
      then calculated the non-linear correlation coefficient h(2) to estimate
      synchronization between EMG signals collected for each contraction. We expressed
      the results by grouping synchronization values by class of term in order to study
      the evolution of this coefficient along gestation. This study has been approved
      by the ethical committee of our hospital. RESULTS: Our results show a non
      significant increase of the h(2) value along term. There is however a trend
      towards an increase of the synchronization of EMG signals as labor approaches but
      not enough to conclude definitively. DISCUSSION AND CONCLUSION: With a
      confirmation of the increase of h(2) along term, the study of the synchronization
      of uterine electrical activity could be an important clue to support the notion
      of myometrial maturation close to labor. Synchronization analysis could also be a
      promising parameter for reliable diagnosis of preterm labor.

PMID- 22483716
TI  - [Arguments against sentinel node procedure in endometrial cancer].

PMID- 22483717
TI  - [Arguments in favour of sentinel lymph node dissection in endometrial cancer].

PMID- 22483718
TI  - [Prospective evaluation of an intravaginal electrical stimulation in the
      treatment of women with pure genuine stress urinary incontinence].
AB  - OBJECTIVES: To study the objective and subjective effectiveness of transvaginal
      electrical stimulation for treatment of female pure genuine stress incontinence.
      PATIENTS AND METHODS: This was a multicenter prospective trial including 207
      patients with genuine stress incontinence who used the stimulator for 10 weeks.
      Similar pre-treatment and post-treatment assessments included both validated
      symptom severity index and health-related quality of life. RESULTS: Objective
      evaluation showed a significant improvement in 65.7% of subjects with stress
      incontinence. All domains of quality of life improved significantly after
      treatment (P=0.0001) and rate of satisfactory was 84.7%. There were no
      statistical differences between the two stimulators. DISCUSSION AND CONCLUSION:
      Pelvic floor electrical stimulation seems to be effective in treating female
      genuine stress incontinence and could be considered first-line therapy.

PMID- 22483719
TI  - Control of seed germination by light-induced histone arginine demethylation
      activity.
AB  - For optimal survival, various environmental and endogenous factors should be
      monitored to determine the appropriate timing for seed germination. Light is a
      major environmental factor affecting seed germination, which is perceived by
      phytochromes. The light-dependent activation of phytochrome B (PHYB) modulates
      abscisic acid and gibberellic acid signaling and metabolism. Thus far, several
      negative regulators of seed germination that act when PHYB is inactive have been
      reported. However, neither positive regulators of seed germination downstream of
      PHYB nor a direct mechanism for regulation of the hormone levels has been
      elucidated. Here, we show that the histone arginine demethylases, JMJ20 and
      JMJ22, act redundantly as positive regulators of seed germination. When PHYB is
      inactive, JMJ20/JMJ22 are directly repressed by the zinc-finger protein SOMNUS.
      However, upon PHYB activation, JMJ20/JMJ22 are derepressed, resulting in
      increased gibberellic acid levels through the removal of repressive histone
      arginine methylations at GA3ox1/GA3ox2, which in turn promotes seed germination.

PMID- 22483720
TI  - Short-term integration of Cdc25 dynamics controls mitotic entry during Drosophila
      gastrulation.
AB  - Cells commit to mitosis by abruptly activating the mitotic cyclin-Cdk complexes.
      During Drosophila gastrulation, mitosis is associated with the transcriptional
      activation of cdc25(string), a phosphatase that activates Cdk1. Here, we
      demonstrate that the switch-like entry into mitosis observed in the Drosophila
      embryo during the 14(th) mitotic cycle is timed by the dynamics of Cdc25(string)
      accumulation. The switch operates as a short-term integrator, a property that can
      improve the reliable control of timing of mitosis. The switch is independent of
      the positive feedback between Cdk1 and Cdc25(string) and of the double negative
      feedback between Cdk1 and Wee1. We propose that the properties of the mitotic
      switch are established by the out-of-equilibrium properties of the covalent
      modification cycle controlling Cdk1 activity. Such covalent modification cycles,
      triggered by transcriptional expression of the activating enzymes, might be a
      widespread strategy to obtain reliable and switch-like control of cell decisions.

PMID- 22483721
TI  - Intravitreal administration of bevacizumab in the treatment of choroidal
      metastasis in a patient with erlotinib-failed pulmonary adenocarcinoma.
AB  - Choroidal metastasis is uncommon and usually identified in a relatively advanced
      cancer status. The median survival after diagnosing choroid metastasis in lung
      cancer patients was only 1.9 months. Once failed to systemic treatment, there was
      no effective local treatment for saving visual acuity. The off-label use of
      intravitreal bevacizumab was popular in treating VEGF-mediated chorioretinal
      diseases worldwide. We here demonstrate a dramatic and durable response to
      intravitreal bevacizumab. Unlike the previous similar reports, our patient had
      failed both first- and second-line therapies.

PMID- 22483722
TI  - Patients with hemispatial neglect are more prone to limb spasticity, but this
      does not prolong their hospital stay.
AB  - OBJECTIVE: To determine whether stroke patients who suffer from hemispatial
      neglect tend to stay in hospitals longer because they are prone to limb
      spasticity. DESIGN: Retrospective analysis of inpatient medical notes. SETTING:
      Inpatient neurorehabilitation unit of a regional UK teaching hospital.
      PARTICIPANTS: All patients (N=106) admitted to the neurorehabilitation unit
      between 2008 and 2010 who had suffered a stroke, as confirmed by computed
      tomography or magnetic resonance imaging. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Statistical coincidence of hemispatial neglect and spasticity;
      length of hospital stay. RESULTS: Chi-square analyses indicated that individuals
      with left neglect were nearly one third more likely to develop spasticity than
      those without neglect (87% vs 57%), while nearly one half of those with left
      sided spasticity showed neglect (44% vs 13%). Individuals with neglect stayed in
      the hospital 45 days longer than those without neglect, but the presence or
      absence of spasticity did not affect length of stay. CONCLUSIONS: The results
      provide the first statistical evidence, to the best of our knowledge, that
      neglect and limb spasticity tend to co-occur poststroke, though it is only the
      former that significantly prolongs stay. Diagnostic value aside, these results
      are important because they tell us that the treatment of neglect should not be
      overshadowed by efforts to reduce comorbid spasticity. Despite its poor
      prognosis, hemispatial neglect continues to receive little targeted therapy in
      some units.

PMID- 22483723
TI  - Therapeutic strategies in post-facial paralysis synkinesis in pediatric patients.
AB  - Synkinetic movements comprise abnormal involuntary contractions of one or more
      facial muscle groups which follow the desired contraction of another facial
      muscle group. They are frequently encountered in patients with long standing
      facial paralysis and seriously affect their psychological status due to the
      impairment of their facial appearance, function and emotional expressivity.
      PATIENTS AND METHODS: Eleven pediatric patients (2 male and 9 female) presenting
      with post-facial paralysis synkinesis were included in the study. Mean age was
      10.3+/-4 years and mean denervation time 72.5 months. RESULTS: Patients underwent
      the following types of treatment: --Cross facial nerve grafting (CFNG) and
      secondary microcoaptations with botulinum toxin injection which had an
      improvement of 100% (3 in the 3 grade synkinesis scale) (n=2). --Cross facial
      nerve grafting (CFNG) and secondary microcoaptations without botulinum toxin
      injection which had an improvement of 66%(2 in the 3 grade synkinesis scale)
      (n=5). --CFNG and direct muscle neurotization with (n=2) or without (n=1)
      botulinum toxin injection where the improvement was 33%. --Contralateral nasalis
      muscle myectomy was performed in one patient along with CFNG and secondary
      microcoaptations which resulted in 66% synkinesis improvement. Biofeedback was
      invariably undertaken by all patients. Postoperative improvement in eye closure
      and smile was also noted in the respective cases treated for synkinesis ranging
      from 25 to 50%, with all patients achieving optimum functional return.
      CONCLUSION: CFNG with secondary microcoaptations and botulinum toxin injections
      was found to be a very efficient surgical modality addressing post-facial palsy
      synkinesis with high improvement in facial function and symmetry. Facial
      neuromuscular re-education contributes considerably in the treatment.

PMID- 22483724
TI  - Contributions of flumequine and nitroarenes to the genotoxicity of river and
      ground waters.
AB  - The SOS/umuC assay was performed in conjunction with analytical measurements to
      identify potential genotoxins in river and adjacent ground waters in the Jialu
      River basin, China. The major genotoxic activities of the river and adjacent
      ground waters occurred in the same two fractions (F4 and F11) when assayed using
      the Salmonella typhimurium strain TA1535/pSK1002. This indicates that ground
      water near the Jialu River was influenced by the river water. LC-MS/MS analysis
      indicated that flumequine accounted for 86% and 76% of the genotoxicity in
      fraction F11 of the river and adjacent ground waters, respectively. When HPLC
      fractions were tested using the strain NM3009, three fractions showed genotoxic
      activities for river water sample, while no fractions from ground water samples
      elicited genotoxic activities. The specific response to the strain NM3009 in one
      fraction compared with the strain TA1535/pSK1002 suggested the presence of
      nitroarenes. However, we failed to identify the exact nitroarenes when GC-MS
      analysis was used to analyze nitroarenes which are well detected in air and soil
      samples in previous papers.

PMID- 22483725
TI  - Solvent extraction for heavy crude oil removal from contaminated soils.
AB  - A new strategy of heavy crude oil removal from contaminated soils was studied.
      The hexane-acetone solvent mixture was used to investigate the ability of solvent
      extraction technique for cleaning up soils under various extraction conditions.
      The mixtures of hexane and acetone (25 vol%) were demonstrated to be the most
      effective in removing petroleum hydrocarbons from contaminated soils and approx
      90% of saturates, naphthene aromatics, polar aromatics, and 60% of nC(7)
      asphaltenes were removed. Kinetic experiments demonstrated that the equilibrium
      was reached in 5 min and the majority of the oil pollutants were removed within
      0.5 min. The effect of the ratio between solvent and soil on the extraction
      efficiency was also studied and results showed that the efficiency would increase
      following the higher solvent soil ratio. Then the multistage continuous
      extraction was considered to enhance the removal efficiency of oil pollutants.
      Three stages crosscurrent and countercurrent solvent extraction with the solvent
      soil ratio 6:1 removed 97% oil contaminants from soil. Clearly the results showed
      that the mixed-solvent of hexane and acetone (25 vol%) with character of low
      toxic, acceptable cost and high efficiency was promising in solvent extraction to
      remove heavy oil fractions as well as petroleum hydrocarbons from contaminated
      soils.

PMID- 22483726
TI  - Assessment of human exposure to benzene through foods from the Belgian market.
AB  - Benzene is a volatile organic compound known to be carcinogenic to humans (Group
      1) and may be present in food. In the present study, 455 food samples from the
      Belgian market were analyzed for benzene contents and some possible sources of
      its occurrence in the foodstuffs were evaluated. Benzene was found above the
      level of detection in 58% of analyzed samples with the highest contents found in
      processed foods such as smoked and canned fish, and foods which contained these
      as ingredients (up to 76.21 MUg kg(-1)). Unprocessed foods such as raw meat,
      fish, and eggs contained much lower concentrations of benzene. Using the benzene
      concentrations in food, a quantitative dietary exposure assessment of benzene
      intake was conducted on a national representative sample of the Belgian
      population over 15 years of age. The mean benzene intake for all foods was 0.020
      MUg kg bw d(-1) according to a probabilistic analysis. These values are below the
      minimum risk level for oral chronic exposure to benzene (0.5 MUg kg bw d(-1)).

PMID- 22483727
TI  - Seasonal fluctuations of DDTs and PCBs in zooplankton and fish of Lake Maggiore
      (Northern Italy).
AB  - Concentrations of DDTs and PCBs were determined in the zooplankton and in three
      different fish species (shad, whitefish and roach) collected seasonally during
      2009 and 2010 in three sites in Lake Maggiore, a south-alpine lake that has been
      contaminated by DDT since 1996. As previously observed in 2008, even during 2009
      DDTs concentrations were higher in zooplankton than in fish, probably due to the
      very unstable situation of the lake still influenced by local inputs. The
      situation changed in 2010, when all DDT compounds increased in fish to levels
      much higher than those measured in zooplankton. Biomagnification was
      statistically demonstrated for pp'DDE in all the three fish species, indicating a
      probable signal of recovery of the lake. Although with respect to total PCBs we
      observed that the contamination levels varied across time periods and across fish
      species, biomagnification was evident from zooplankton to fish both in 2009 and
      in 2010. As concern individual PCBs, biomagnification from zooplankton to all
      three fish species was significant for PCB 153 and PCB 138.

PMID- 22483728
TI  - Photoelectrocatalytic degradation of recalcitrant organic pollutants using TiO2
      film electrodes: an overview.
AB  - Photoelectrocatalytic (PEC) technology involved applying an electrical bias to a
      TiO(2) film electrode, has been widely applied to the degradation of refractory
      organic pollutants, owing to its high degradation efficiency. This paper reviews
      recent developments in the PEC degradation of recalcitrant organic contaminants
      using a TiO(2) film electrode. The preparation and application of various TiO(2)
      film electrodes have been investigated, as well as the parameters that influence
      PEC activity such as the crystal structure, the film thickness and substrate
      material, the applied electrical bias, the solution pH and conductivity. The
      improvement of PEC activity by doping the TiO(2) film electrode with metal and
      non-metal ions has been discussed. The mechanism and kinetics for the PEC
      degradation of organic pollutants have also been highlighted.

PMID- 22483729
TI  - Bioconcentration of triclosan, methyl-triclosan, and triclocarban in the plants
      and sediments of a constructed wetland.
AB  - Constructed wetlands are a potential method for the removal of two pharmaceutical
      and personal care products from wastewater effluent. Triclosan (TCS; 5-chloro-2
      [2,4-dichlorophenoxy]phenol) and triclocarban (TCC; 3,4,4'-trichlorocarbanillide)
      are antimicrobial agents added to a variety of consumer products whose
      accumulation patterns in constructed wetlands are poorly understood. Here, we
      report the accumulation of TCS, its metabolite methyl-triclosan (MTCS; 5-chloro-2
      [2,4-dichlorophenoxy]), and TCC in wetland plant tissues and sediments. Three
      wetland macrophytes: Typha latifolia, Pontederia cordata, and Sagittaria graminea
      were sampled from a constructed wetland in Denton, Texas, USA. MTCS
      concentrations were below the method detection limit (MDL) for all species. TCS
      root tissue concentrations in T. latifolia were significantly greater than root
      concentrations in P. cordata (mean+/-SE in ng g(-1): 40.3+/-11.3 vs. 15.0+/-1.9,
      respectively), while for TCC, shoot tissue concentrations in S. graminea were
      significantly greater than in T. latifolia (22.8+/-9.3 vs. 9.0 (MDL),
      respectively). For both TCS and TCC, T. latifolia root tissue concentrations were
      significantly greater than shoot concentrations (TCS: 40.3+/-11.3 vs. 17.2+/-0.2,
      TCC: 26.0+/-3.6 vs. 9.0, (MDL)). TCC concentrations in P. cordata roots were
      significantly greater than in shoots (34.4+/-5.3 vs. 15.4+/-2.8, respectively).
      TCS concentrations in T. latifolia roots and sediments and TCC concentrations in
      sediments generally decreased from wetland inflow to outflow. To our knowledge,
      this is the first study documenting species and tissue specific differences in
      the accumulation of TCS and TCC in plants from an operational constructed
      wetland. The species specific differences in bioaccumulation suggest TCS and TCC
      removal from constructed wetlands could be enhanced through targeted plantings.

PMID- 22483730
TI  - Perfluoroalkyl and polyfluoroalkyl substances (PFASs) in consumer products in
      Norway - a pilot study.
AB  - Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are used in numerous
      industrial and consumer products because of their special chemical properties,
      for instance the ability to repel both water and oil. A broad variety of PFAS
      have been introduced into the Norwegian market through industrial use (e.g. via
      fire fighting foams and paints) as well as in treated customer products such as
      textiles and coated paper. Our present knowledge of the exact chemical PFAS
      compositions in preparations using perfluorinated compounds is limited. This lack
      of knowledge means that it is difficult to provide an accurate assessment of
      human exposure to these compounds or to the amount of waste that may contain
      treated products. It is a growing concern that these potentially harmful
      compounds can now be found throughout the global environment. Samples of consumer
      products and preparations were collected in Norway, with supplemental samples
      from Sweden. In 27 of the 30 analyzed consumer products and preparations a number
      of polyfluorinated substances that were analyzed were detected but this does not
      exclude the occurrence of unknown PFAS. Notable was that
      perfluorooctanesulphonate (PFOS), which has been strictly regulated in Norway
      since 2007, was found in amounts close to or exceeding the EU regulatory level in
      4 of the 30 analyzed products, all within the leather or carpet product groups.
      High amounts of fluorotelomer alcohols (FTOHs) were found in waterproofing
      agents, carpets and textiles, consistent with earlier findings by Fiedler et al.
      (2010). The presence of PFAS in a broad range of consumer products can give rise
      to a constant diffuse human exposure that might eventually result in harm to
      humans.

PMID- 22483731
TI  - Blood dioxin biomonitoring to assess local residents' exposure from a large urban
      remediation project.
AB  - BACKGROUND: A total of 265000 m(3) of dioxin contaminated soil and sediments from
      past industrial activity was treated on site in an urban setting in Sydney,
      Australia. To respond to local community concerns about potential dioxin exposure
      from fugitive emissions a human biomonitoring study was undertaken. OBJECTIVE: To
      determine whether local residents were exposed to significant amounts of dioxin
      from the remediation process. METHODS: Blood samples were collected from local
      residents around the site and a representative metropolitan control group. They
      were pooled within age and sex strata and the change in dioxin concentrations
      over the remediation period and a summary of the mid point and post remediation
      dioxin concentrations were compared between groups. Information on dietary intake
      was collected to look for possible confounding. RESULTS: The mean dioxin Toxic
      Equivalent concentrations (TeQ) decreased among both the local resident and
      control groups over the remediation period by 1.9 and 2.1 pg gm(-1) lipid
      respectively. Modelled blood concentrations adjusting for age and sex did not
      detect a significant difference between groups for changes in either TeQ or
      2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8 TCDD). The summary measure approach
      did however demonstrate that the 2,3,7,8 TCDD concentrations among the local
      resident group was approximately 0.7 pg g(-1) lipid higher compared to the
      control group post remediation. There were no significant changes in dietary
      intake sources of dioxin. CONCLUSION: Biomonitoring demonstrated that local
      residents were not exposed to significant quantities of dioxin. Large scale
      remediation of dioxin contaminated land can be safely undertaken in an urban
      setting.

PMID- 22483732
TI  - Lack of association between factor V Leiden and prothrombin G20210A polymorphisms
      in Tunisian subjects with a history of myocardial infarction.
AB  - BACKGROUND: Myocardial infarction is a multifactorial disease. It is provoked by
      occlusions in the coronary arteries resulting from exposure to multiple risk
      factors. OBJECTIVE: To study the risk of myocardial infarction associated with
      the gene polymorphisms of factor V Leiden and factor II (G20210A). MATERIALS AND
      METHODS: Cases consisted of 100 myocardial infarction patients who were
      hospitalized in the Principal Military Hospital of Tunis and 200 control subjects
      with no history of myocardial infarction. RESULTS: The prevalence of the factor V
      Leiden was higher in myocardial infarction patients (9%) than in control subjects
      (6%) with an OR=1.55 (95% CI=0.58-4.12), whereas the prevalence of prothrombin
      G20210A mutation was 3% and 2.5% in the patient and control groups, respectively
      [OR=1.21 (95% CI=0.22-5.94)]. CONCLUSION: Our results indicate that neither
      factor V Leiden nor the prothrombin G20210A contributed to the risk factors for
      myocardial infarction.

PMID- 22483733
TI  - Complications of wrist arthroscopy.
AB  - PURPOSE: The purpose of this systematic review was to address the incidence of
      complications associated with wrist arthroscopy. Given the paucity of information
      published on this topic, an all-inclusive review of published wrist arthroscopy
      complications was sought. METHODS: Two independent reviewers performed a
      literature search using PubMed, Google Scholar, EBSCO, and Academic Megasearch
      using the terms "wrist arthroscopy complications," "complications of wrist
      arthroscopy," "wrist arthroscopy injury," and "wrist arthroscopy." Inclusion
      criteria were (1) Levels I to V evidence, (2) "complication" defined as an
      adverse outcome directly related to the operative procedure, and (3) explicit
      description of operative complications in the study. RESULTS: Eleven multiple
      patient studies addressing complications of wrist arthroscopy from 1994 to 2010
      were identified, with 42 complications reported from 895 wrist arthroscopy
      procedures, a 4.7% complication rate. Four case reports were also found,
      identifying injury to the dorsal sensory branch of the ulnar nerve, injury to the
      posterior interosseous nerve, and extensor tendon sheath fistula formation.
      CONCLUSIONS: This systematic review suggests that the previously documented rate
      of wrist arthroscopy complications may be underestimating the true incidence. The
      report of various complications provides insight to surgeons for improving future
      surgical techniques. LEVEL OF EVIDENCE: Level IV, systematic review of Levels I-V
      studies.

PMID- 22483734
TI  - Revision arthroscopic rotator cuff repair: systematic review and authors'
      preferred surgical technique.
AB  - PURPOSE: Recurrent tear after rotator cuff repair is not uncommon. Advances in
      arthroscopic shoulder surgery have created opportunities to better evaluate and
      treat these failures. The purposes of this systematic review were to evaluate the
      reported results of revision arthroscopic rotator cuff repair (ARCR) and to
      describe our technique of revision ARCR. METHODS: A PubMed search from 1950 to
      2011 was performed to identify articles describing revision rotator cuff repair.
      Studies were included in this systematic review if (1) they focused on revision
      ARCR, (2) they provided Levels I-IV evidence relevant to the search terms, (3) at
      least a partial repair was performed, and (4) they had a minimum of 12 months'
      follow-up. RESULTS: We identified 4 articles that discussed the techniques and
      the results of revision ARCR. In all studies there were improvements in
      postoperative motion and functional outcome scores. Poorer results were
      associated with female patients, tear recurrence after revision repair,
      preoperative active forward flexion of less than 135 degrees , and preoperative
      pain score greater than 5 on a visual analog scale. CONCLUSIONS: This systematic
      review suggests that revision ARCR can frequently lead to improvement in
      functional outcome and reasonable patient satisfaction. LEVEL OF EVIDENCE: Level
      IV, systematic review of Level IV studies.

PMID- 22483735
TI  - Arthroscopic matrix-induced autologous chondrocyte implantation: 2-year outcomes.
AB  - PURPOSE: To determine the safety and efficacy of a new arthroscopic technique for
      matrix-induced autologous chondrocyte implantation (MACI) for articular cartilage
      defects in the knee. METHODS: We undertook a prospective evaluation of the first
      20 patients treated with the MACI technique (including 14 defects on the femoral
      condyle and 6 on the tibial plateau), followed up for 24 months after surgery. A
      12-week structured rehabilitation program was undertaken by all patients.
      Patients underwent clinical assessment (Knee Injury and Osteoarthritis Outcome
      Score, Short Form 36 Health Survey, visual analog pain scale, 6-minute walk test,
      knee range of motion) before surgery and at 3, 6, 12, and 24 months after surgery
      and underwent magnetic resonance imaging (MRI) assessment at 3, 12, and 24 months
      after surgery. MRI evaluation assessed 8 previously defined pertinent parameters
      of graft repair, as well as a combined MRI composite score. RESULTS: A
      significant improvement (P < .05) was shown throughout the postoperative time
      line for all Knee Injury and Osteoarthritis Outcome Score subscales, the physical
      component score of the Short Form 36 Health Survey, the frequency and severity of
      knee pain, and the 6-minute walk test. An improvement in pertinent morphologic
      parameters of graft repair was observed to 24 months, whereas a good to excellent
      graft infill score and MRI composite score were observed at 24 months after
      surgery in 90% and 70% of patients, respectively. CONCLUSIONS: We report a
      comprehensive 24-month follow-up in the first 20 patients who underwent the
      arthroscopic MACI technique. This technique is a safe and efficacious procedure
      with improved clinical and radiologic outcomes over the 2-year period.

PMID- 22483736
TI  - Site of non-photochemical quenching of the phycobilisome by orange carotenoid
      protein in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - In cyanobacteria, the thermal dissipation of excess absorbed energy at the level
      of the phycobilisome (PBS)-antenna is triggered by absorption of strong blue
      green light by the photoactive orange carotenoid protein (OCP). This process
      known as non-photochemical quenching, whose molecular mechanism remains in many
      respects unclear, is revealed in vivo as a decrease in phycobilisome
      fluorescence. In vitro reconstituted system on the interaction of the OCP and the
      PBS isolated from the cyanobacterium Synechocystis sp. PCC 6803 presents evidence
      that the OCP is not only a photosensor, but also an effecter that makes direct
      contacts with the PBS and causes dissipation of absorbed energy. To localize the
      site(s) of quenching, we have analyzed the role of chromophorylated polypeptides
      of the PBS using PBS-deficient mutants in conjunction with in vitro systems of
      assembled PBS and of isolated components of the PBS core. The results
      demonstrated that L(CM), the core-membrane linker protein and terminal emitter of
      the PBS, could act as the docking site for OCP in vitro. The ApcD and ApcF
      terminal emitters of the PBS core are not directly subjected to quenching. The
      data suggests that there could be close contact between the phycocyanobilin
      chromophore of L(CM) and the 3'-hydroxyechinenone chromophore present in OCP and
      that L(CM) could be involved in OCP-induced quenching. According to the reduced
      average life-time of the PBS-fluorescence and linear dependence of fluorescence
      intensity of the PBS on OCP concentration, the quenching has mostly dynamic
      character. This article is part of a Special Issue entitled: Photosynthesis
      Research for Sustainability: from Natural to Artificial.

PMID- 22483737
TI  - Radiation Therapy Oncology Group consensus panel guidelines for the delineation
      of the clinical target volume in the postoperative treatment of pancreatic head
      cancer.
AB  - PURPOSE: To develop contouring guidelines to be used in the Radiation Therapy
      Oncology Group protocol 0848, a Phase III randomized trial evaluating the benefit
      of adjuvant chemoradiation in patients with resected head of pancreas cancer.
      METHODS AND MATERIALS: A consensus committee of six radiation oncologists with
      expertise in gastrointestinal radiotherapy developed stepwise contouring
      guidelines and an atlas for the delineation of the clinical target volume (CTV)
      in the postoperative treatment of pancreas cancer, based on identifiable regions
      of interest and margin expansions. Areas at risk for subclinical disease to be
      included in the CTV were defined, including nodal regions, anastomoses, and the
      preoperative primary tumor location. Regions of interest that could be
      reproducibly contoured on postoperative imaging after a pancreaticoduodenectomy
      were identified. Standardized expansion margins to encompass areas at risk were
      developed after multiple iterations to determine the optimal margin expansions.
      RESULTS: New contouring recommendations based on CT anatomy were established.
      Written guidelines for the delineation of the postoperative CTV and normal
      tissues, as well as a Web-based atlas, were developed. CONCLUSIONS: The
      postoperative abdomen has been a difficult area for effective radiotherapy. These
      new guidelines will help physicians create fields that better encompass areas at
      risk and minimize dose to normal tissues.

PMID- 22483738
TI  - Phase II trial of hypofractionated IMRT with temozolomide for patients with newly
      diagnosed glioblastoma multiforme.
AB  - PURPOSE: To report toxicity and overall survival (OS) in patients with newly
      diagnosed glioblastoma multiforme (GBM) treated with hypofractionated intensity
      modulated radiotherapy (hypo-IMRT) with concurrent and adjuvant temozolomide
      (TMZ). METHODS AND MATERIALS: Patients with newly diagnosed GBM after biopsy or
      resection and with adequate performance status and organ or bone marrow function
      were eligible for this study. Patients received postoperative hypo-IMRT to the
      surgical cavity and residual tumor seen on T1-weighted brain MRI with a 5-mm
      margin to a total dose of 60 Gy in 10 fractions (6 Gy/fraction) and to the T2
      abnormality on T2-weighted MRI with 5-mm margin to 30 Gy in 10 fractions (3
      Gy/fraction). Concurrent TMZ was given at 75 mg/m(2)/day for 28 consecutive days.
      Adjuvant TMZ was given at 150 to 200 mg/m(2)/day for 5 days every 28 days.
      Toxicities were defined using Common Terminology Criteria for Adverse Events
      version 3.0. RESULTS: Twenty-four patients were treated, consisting of 14 men, 10
      women; a median age of 60.5 years old (range, 27-77 years); and a median
      Karnofsky performance score of 80 (range, 60-90). All patients received hypo-IMRT
      and concurrent TMZ according to protocol, except for 2 patients who received only
      14 days of concurrent TMZ. The median number of adjuvant TMZ cycles was 6.5
      (range, 0-14).With a median follow-up of 14.8 months (range, 2.7-34.2 months) for
      all patients and a minimum follow-up of 20.6 months for living patients, no
      instances of grade 3 or higher nonhematologic toxicity were observed. The median
      OS was 16.6 months (range, 4.1-35.9 months). Six patients underwent repeated
      surgery for suspected tumor recurrence; necrosis was found in 50% to 100% of the
      resected specimens. CONCLUSION: In selected GBM patients, 60 Gy hypo-IMRT
      delivered in 6-Gy fractions over 2 weeks with concurrent and adjuvant TMZ is
      safe. OS in this small cohort of patients was comparable to that treated with
      current standard of care therapy.

PMID- 22483740
TI  - Ultrasonics promoted synthesis of thiazolidinones from 2-aminopyridine and 2
      picolilamine.
AB  - The efficient multicomponent synthesis of thiazolidinones from the reaction of
      arenealdehydes, mercaptoacetic acid and 2-picolilamine or 2-aminopyridine under
      ultrasound irradiation are reported. The reaction with 2-aminopyridine needs a
      Lewis acid catalysis to afford the corresponding 2-aryl-3-(pyridin-2-yl)-1,3
      thiazolidin-4-ones. All novel compounds were identified and characterized by (1)H
      and (13)C NMR spectra. Applying the sonochemical methodology, two series of
      heterocyclic thiazolidinones were synthesized in good yields after short reaction
      times.

PMID- 22483739
TI  - Assessment of MRI parameters as imaging biomarkers for radiation necrosis in the
      rat brain.
AB  - PURPOSE: Radiation necrosis is a major complication of radiation therapy. We
      explore the features of radiation-induced brain necrosis in the rat, using
      multiple MRI approaches, including T(1), T(2), apparent diffusion constant (ADC),
      cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton
      transfer (APT) of endogenous mobile proteins and peptides. METHODS AND MATERIALS:
      Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X
      ray beam (40 Gy; 10 * 10 mm(2)) in the left brain hemisphere. MRI was acquired on
      a 4.7-T animal scanner at ~25 weeks' postradiation. The MRI signals of necrotic
      cores and perinecrotic regions were assessed with a one-way analysis of variance.
      Histological evaluation was accomplished with hematoxylin and eosin staining.
      RESULTS: ADC and CBF MRI could separate perinecrotic and contralateral normal
      brain tissue (p < 0.01 and < 0.05, respectively), whereas T(1), T(2), MTR, and
      APT could not. MRI signal intensities were significantly lower in the necrotic
      core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and
      insignificantly higher or lower for T(1), T(2), MTR, and ADC. Histological
      results demonstrated coagulative necrosis within the necrotic core and reactive
      astrogliosis and vascular damage within the perinecrotic region. CONCLUSION: ADC
      and CBF are promising imaging biomarkers for identifying perinecrotic regions,
      whereas CBF and APT are promising for identifying necrotic cores.

PMID- 22483741
TI  - Kin conflict in insect societies: a new epigenetic perspective.
AB  - The social hymenopterans (ants, wasps and bees) have all the enzymatic and
      genetic mechanisms necessary for the functional modification of DNA by
      methylation. Methylation appears to play a central role in shaping the
      developmental processes that give rise to the different castes. However, could
      DNA methylation have other roles in social insects? Theoretical arguments predict
      that male and female hymenopterans can be in conflict over the reproductive
      potential of their female offspring. An exciting prospect for future research is
      to examine the possibility that queens and males imprint the genomes of their
      gametes using DNA methylation to manipulate the reproductive potential of their
      progeny in ways that favour the inclusive fitness of the parent.

PMID- 22483742
TI  - Activation of the hippocampal complex during tactile maze solving in congenitally
      blind subjects.
AB  - Despite their lack of vision, congenitally blind subjects are able to build and
      manipulate cognitive maps for spatial navigation. It is assumed that they thereby
      rely more heavily on echolocation, proprioceptive signals and environmental cues
      such as ambient temperature and audition to compensate for their lack of vision.
      Little is known, however, about the neural mechanisms underlying spatial
      navigation in blind individuals in settings where these cues are absent. We
      therefore measured behavioural performance and blood oxygenation-level dependant
      (BOLD) responses using functional magnetic resonance imaging (fMRI) in
      congenitally blind and blindfolded sighted participants while they navigated
      through a tactile multiple T-maze. Both groups learned the maze task at a similar
      pace. In blind participants, tactile maze navigation was associated with
      increased BOLD responses in the right hippocampus and parahippocampus, occipital
      cortex and fusiform gyrus. Blindfolded sighted controls did not show increased
      BOLD responses in these areas; instead they activated the caudate nucleus and
      thalamus. Both groups activated the precuneus during tactile maze navigation. We
      conclude that cross-modal plastic processes allow for the recruitment of the
      hippocampal complex and visual cortex in congenital blindness.

PMID- 22483743
TI  - Reducing the inhalation dose from radon decay products.

PMID- 22483744
TI  - Separation of polybrominated diphenyl ethers in fish for compound-specific stable
      carbon isotope analysis.
AB  - A separation and isotopic analysis method was developed to accurately measure the
      stable carbon isotope ratios of polybrominated diphenyl ethers (PBDEs) with three
      to six substituted bromine atoms in fish samples. Sample extracts were treated
      with concentrated sulfuric acid to remove lipids, purified using complex silica
      gel column chromatography, and finally processed using alumina/silica (Al/Si) gel
      column chromatography. The purities of extracts were verified by gas
      chromatography and mass spectrometry (GC-MS) in the full-scan mode. The average
      recoveries of all compounds across the purification method were between 60% and
      110%, with the exception of BDE-154. The stable carbon isotopic compositions of
      PBDEs can be measured with a standard deviation of less than 0.50/00. No
      significant isotopic fraction was found during the purification of the main PBDE
      congeners. A significant change in the stable carbon isotope ratio of BDE-47 was
      observed in fish carcasses compared to the original isotopic signatures, implying
      that PBDE stable carbon isotopic compositions can be used to trace the
      biotransformation of PBDEs in biota.

PMID- 22483745
TI  - The role of differences in individual and community attributes in perceived air
      quality.
AB  - Most epidemiological studies on the adverse effects of air pollution on health
      have focused on scientific measurements of air quality provided by monitoring
      stations. However, many studies have indicated that self-reported health status,
      such as disease severity and depressive symptoms, are associated with perceived
      air pollution rather than measured air pollution. The main goal of this study was
      to investigate social factors that may affect perceived local air quality using a
      multilevel analysis among a Korean population. We used the Seoul Citizens Health
      Indicator Survey (SCHIS III) and five air pollutants. The total study population
      was 16,041. We considered individual-level and community-level variables that may
      affect perceived air quality, such as the percentage of college-educated
      individuals aged >20 years, satisfaction with public transportation, and the
      percentage of individuals below the poverty line. Measured air quality showed a
      negative or neutral relationship with perceived air quality. We found that the
      degree of perceived air pollution was associated with younger age (20-34 years;
      OR=1.40, 95% CI=1.18-1.65), married and divorced/separated/widowed people, a
      higher level of education (>17 years; OR=1.67, 95% CI=1.30-2.15), and lower
      household income. Communities that were more economically deprived were
      associated with poor perceived air quality. Differences in individual and
      community characteristics affected perceived air quality. Perception is a key
      factor influencing the public acceptance of environmental policy. This study may
      help policymakers understand the social distribution of environmental awareness.

PMID- 22483746
TI  - Life cycle assessment of engineered nanomaterials: state of the art and
      strategies to overcome existing gaps.
AB  - The use of engineered nanomaterials offers advantages as well as disadvantages
      from a sustainability perspective. It is important to identify such points as
      early as possible in order to be able to build on existing strengths, while
      counteracting disadvantages. Life Cycle Assessment (LCA) is a suitable method to
      assess the environmental performance of a product or process. But so far studies
      applying LCA to the area of nanotechnology have been scarce. One reason might be
      that the LCA framework has a whole list of issues that need further precision in
      order to be applicable to nanotechnologies: system boundaries and a functional
      unit have to be chosen in a way that allows one to do a comparison of equal
      functionalities; adequate and comprehensive life cycle inventory data for
      engineered nanomaterials are the key on the level of inventory analysis; and the
      impact assessment step requires a clear definition of the degree of detail on the
      level of nanoparticle emissions. The LCA studies existing thus far in the area of
      nanotechnology have barely begun to cover all these aspects. Thus, in order to
      improve the current situation, the authors propose to go ahead in each of the LCA
      stages as far as scientific advances allow. For the inventory modelling this
      means e.g. that comprehensive, transparently documented and quality ensured data
      of the most important engineered nanomaterials should be collected and made
      available in a widely-accepted format. Concerning nanoparticle emissions, as many
      parameters as possible have to be collected pertaining to the production, use,
      and the disposal phase of these engineered nanomaterials. Furthermore, on the
      level of impact assessment, relevant physical characteristics have to be
      identified for a toxicity assessment of nanoparticles and a consensus has to be
      found for a limited but sufficient number of independent parameters influencing
      toxicity to be collected.

PMID- 22483747
TI  - A comparative study of the effects of ozonation and TiO2-catalyzed ozonation on
      the selected chlorine disinfection by-product precursor content and structure.
AB  - This study compares the effects of ozonation (0.4-3.0 mg O(3)/mg DOC) and TiO(2)
      catalyzed ozonation - TiO(2)-O(3) (0.4-3.0 mgO(3)/mg DOC; 1.0 mgTiO(2)/L) at pH 6
      on the content and structure of natural organic matter (NOM) and trihalometane
      (THM) and haloacetonitrile (HAN) precursors in groundwater. The investigated
      groundwater from Northern Serbia is rich in NOM (9.85 mg/L DOC) which is mostly
      of hydrophobic character (65% fulvic acid and 14% humic acid fraction). It was
      found that the TiO(2)-catalyzed process, by favoring the radical mechanism of NOM
      oxidation, resulted in a more effective reduction in the content of total NOM (up
      to 18% DOC) compared to ozonation alone (up to 6% DOC). The use of TiO(2) also
      resulted in an improvement of ozonation in terms of THM precursor content removal
      (up to 80%). On the other hand, the application of both oxidation treatments
      resulted in an increase in the HANFP compared to the raw water. NOM oxidation
      during ozonation and TiO(2)-O(3) caused changes in their structure in the
      direction of an increased proportion of the hydrophilic fraction (up to 70%),
      which has the most reactive THM and HAN precursors, as well as the fraction with
      the highest content of their brominated species.

PMID- 22483748
TI  - [Acute postinfectious glomerulonephritis].
AB  - Acute postinfectious glomerulonephritis are defined by an acute nonsuppurative
      inflammatory insult predominantly glomerular. Its current incidence is uncertain
      because of the frequency of subclinical forms. The most common infectious agent
      involved is beta hemolytic streptococcus group A. Acute postinfectious
      glomerulonephritis is uncommon in adults, and its incidence is progressively
      declining in developed countries. Humoral immunity plays a key role in the
      pathogenesis of kidney damage. Complement activation by the alternative pathway
      is the dominant mechanism, but a third way (lectin pathway) has been recently
      identified. The classic clinical presentation is sudden onset of acute nephritic
      syndrome after a free interval from a streptococcal infection. Treatment is
      essentially symptomatic and prevention is possible through improved hygiene and
      early treatment of infections.

PMID- 22483749
TI  - The effect of insulin therapy on biomechanical deterioration of bone in
      streptozotocin (STZ)-induced type 1 diabetes mellitus in rats.
AB  - AIMS: To investigate the effect of insulin therapy on biomechanical properties of
      bone in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) in rats.
      METHODS: A total of 28 male Wistar-Albino rats (12-week-old; 210-300g) were
      divided into 4 groups (n=7 for each) including control [C; no treatment], sham
      [Sh; distilled water i.p., for 8 weeks], diabetes [T1DM; 65mg/kg of STZ, single
      i.p.] and diabetes+insulin treatment [T1DM+I; 65mg/kg of STZ, single
      i.p.+insulin; 2-4UI/day/rat, i.p., for 8 weeks] groups. Body weight, blood
      glucose levels (BGLs), bone mineral density (BMD) and geometric/mechanical
      properties of bone tissue were evaluated. RESULTS: BGLs in diabetic rats were
      significantly increased compared to non-diabetic rats, while the body weights
      were decreased (p<0.05). Femur length and cross-sectional area of femur were
      significantly decreased in both T1DM and T1DM+I groups (p<0.05). The significant
      reduction obtained in BMD in T1DM rats compared with C and Sh (p<0.05) groups was
      reversed by insulin treatment (p<0.05). Displacement, absorbed energy, maximum
      load, ultimate stress and toughness were significantly decreased inT1DM and
      T1DM+I groups compared to C and Sh groups (p<0.05). CONCLUSIONS: In conclusion,
      insulin treatment seems to be ineffective in restoration of biomechanical
      deterioration of bone specific to STZ-induced T1DM.

PMID- 22483750
TI  - Regulation of the glutamate transporter EAAT3 by mammalian target of rapamycin
      mTOR.
AB  - The serine/threonine kinase mammalian target of rapamycin (mTOR) is stimulated by
      insulin, growth factors and nutrients and confers survival of several cell types.
      The kinase has previously been shown to stimulate amino acid uptake. In neurons,
      the cellular uptake of glutamate by the excitatory amino-acid transporters
      (EAATs) decreases excitation and thus confers protection against excitotoxicity.
      In epithelia, EAAT3 accomplishes transepithelial glutamate and aspartate
      transport. The present study explored, whether mTOR regulates EAAT3 (SLC1A1). To
      this end, cRNA encoding EAAT3 was injected into Xenopus oocytes with or without
      cRNA encoding mTOR and the glutamate induced current (I(glu)), a measure of
      glutamate transport, determined by dual electrode voltage clamp. Moreover, EAAT3
      protein abundance was determined utilizing chemiluminescence. As a result, I(glu)
      was observed in Xenopus oocytes expressing EAAT3 but not in water injected
      oocytes. Coexpression of mTOR significantly increased I(glu), an effect reversed
      by rapamycin (100 nM). mTOR coexpression increased EAAT3 protein abundance in the
      cell membrane. The decay of I(glu) following inhibition of carrier insertion with
      brefeldin A in oocytes coexpressing EAAT3 with mTOR was similar in the presence
      and absence of rapamycin (100 nM). In conclusion, mTOR is a novel powerful
      regulator of EAAT3 and may thus contribute to protection against
      neuroexcitotoxicity.

PMID- 22483751
TI  - Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive
      oxygen species.
AB  - Mitochondrial reactive oxygen species (mROS) are involved in cancer initiation
      and progression and function as signaling molecules in many aspects of hypoxia
      and growth factor-mediated signaling. Here we report that matairesinol, a natural
      small molecule identified from the cell-based screening of 200 natural plants,
      suppresses mROS generation resulting in anti-angiogenic activity. A non-toxic
      concentration of matairesinol inhibited the proliferation of human umbilical vein
      endothelial cells. The compound also suppressed in vitro angiogenesis of tube
      formation and chemoinvasion, as well as in vivo angiogenesis of the
      chorioallantoic membrane at non-toxic doses. Furthermore, matairesinol decreased
      hypoxia-inducible factor-1alpha in hypoxic HeLa cells. These results demonstrate
      that matairesinol could function as a novel angiogenesis inhibitor by suppressing
      mROS signaling.

PMID- 22483752
TI  - Identification and characterization of a novel Ribose 5-phosphate isomerase B
      from Leishmania donovani.
AB  - Leishmaniasis is a group of tropical diseases caused by protozoan parasites of
      the genus Leishmania. Due to the emergence of resistance to the available
      antileishmanial drugs there is an immediate need to identify molecular targets on
      which to base future treatment strategies. Ribose 5-phosphate isomerase (Rpi; EC
      5.3.1.6) is a key enzyme of the pentose phosphate pathway (PPP) which catalyses
      the reversible aldose-ketose isomerization between Ribose 5-phosphate (R5P) and
      Ribulose 5-phosphate (Ru5P). It exists in two isoforms A and B. These two are
      completely unrelated enzymes catalyzing the same reaction. Analysis of the
      Leishmania infantum genome revealed that though the RpiB gene is present, RpiA
      homologs are completely absent. An absence of RpiBs in the genomes of higher
      animals makes this enzyme a possible target for the chemotherapy of
      Leishmaniasis. In this paper, we report for the first time the presence of B
      isoform of the Rpi enzyme in Leishmania donovani (LdRpiB) by cloning and
      molecular characterization of the enzyme. An amplified L. donovani RpiB gene is
      519 bp and encodes for a putative 172 amino acid protein with a molecular mass of
      ~19 kDa. An ~19 kDa protein with poly-His tag at the C-terminal end was obtained
      by heterologous expression of LdRpiB in Escherichia coli. The recombinant form of
      RpiB was obtained in soluble and active form. The LdRpiB exists as a dimer of
      dimers i.e. the tetramer form. The polyclonal antibody against Trypanosoma cruzi
      RpiB could detect a band of ~19 kDa with the purified recombinant RpiB as well as
      native RpiB from the L. donovani promastigotes. Recombinant RpiB obeys the
      classical Michaelis-Menten kinetics utilizing R5P as the substrate with a K(m)
      value of 2.4+/-0.6 mM and K(cat) value of 30+/-5.2 s(-1). Our study confirms the
      presence of Ribose 5-phosphate isomerase B in L. donovani and provides functional
      characterization of RpiB for further validating it as a potential drug target.

PMID- 22483753
TI  - IQGAP1 interacts with Aurora-A and enhances its stability and its role in cancer.
AB  - IQGAP1, a ubiquitously expressed scaffold protein, has been identified in a wide
      range of organisms. It participates in multiple aspects of cellular events by
      binding to and regulating numerous interacting proteins. In our present study, we
      identified a new IQGAP1 binding protein named Aurora-A which is an oncogenic
      protein and overexpressed in various types of human tumors. In vitro analysis
      with GST-Aurora-A fusion proteins showed a physical interaction between Aurora-A
      and IQGAP1. Moreover, the binding also occurred in HeLa cells as endogenous
      Aurora-A co-immunoprecipitated with IQGAP1 from the cell lysates. Overexpression
      of IQGAP1 resulted in an elevation of both expression and activity of Aurora-A
      kinase. Endogenous IQGAP1 knockdown by siRNA promoted Aurora-A degradation
      whereas IQGAP1 overexpression enhanced the stability of Aurora-A. Additionally,
      we documented that the IQGAP1-induced cell proliferation was suppressed by
      knocking down Aurora-A expression. Taken together, our results showed an
      unidentified relationship between Aurora-A and IQGAP1, and provided a new insight
      into the molecular mechanism by which IQGAP1 played a regulatory role in cancer.

PMID- 22483754
TI  - [Nutritional assessment of patients before surgery].
AB  - The identification of nutritional status is one of the objectives of the
      anaesthesia consultation often difficult to achieve routinely. It usually
      requires the use of multiple indicators, which are complex for a non-nutrition
      specialist. In preoperative period, nutritional assessment should be easy to do
      in order to identify patients who are malnourished or at risk of malnutrition and
      relevant information about nutritional risk should be registered in the patient
      chart. To facilitate this evaluation, we propose a stratification of nutritional
      risk in four grades (NG) using three types of simple and validated parameters:
      preoperative nutritional status (BMI, weight loss, eventually serum albumin),
      comorbidities and kind of surgery. This stratification can develop a tailored
      nutritional care for each patient.

PMID- 22483755
TI  - [Videolaryngoscopy, for everybody?].

PMID- 22483756
TI  - [Assessment of mortality morbidity conference in obstetrics: literature review].
AB  - OBJECTIVES: To assess this effectiveness of morbi-mortality conference (MMC) in
      improving quality of care. MATERIALS AND METHODS: A review was carried out by
      searching Medline, Pascal and Cochrane databases, Google scholar and websites of
      French obstetrics professional societies, until July 2011. Search terms included
      morbidity, mortality, conference, and obstetrics. The eligible reports of
      assessment of MMC in obstetrics have been analysed by four reviewers with a
      standardized form. RESULTS: Among 319 records identified, four observational
      studies published between 2009 and 2011 were included. The objective of these MMC
      was students' training (n=2), quality of care improvement (n=1), or both (n=1).
      The MMC organization was heterogeneous. The impact of MMC was assessed using
      qualitative (n=2), semi-quantitative (n=1) or quantitative (n=1) method. None of
      these studies showed a significant impact of MMC on students' training or quality
      of care. CONCLUSION: Available evidence is insufficient to evaluate the
      effectiveness of MMC in improving quality of obstetrics care.

PMID- 22483757
TI  - The important roles of tissue anisotropy and tissue-to-tissue contact on the
      dynamical behavior of a symmetric tri-leaflet valve during multiple cardiac
      pressure cycles.
AB  - Restricting our scope to the dynamical motion of the leaflets, we present a
      computational model for a symmetric, tri-leaflet, bioprosthetic heart valve (BHV)
      at the end of five complete cardiac pressure cycles, reaching the steady state of
      deformation during both closing and opening phases. To this end, we utilized a
      highly anisotropic material model for the large deformation behavior of the
      tissue material, for which an experimental validation was provided. The important
      findings are: (1) material anisotropy has significant effect on the valve
      opening/closing; (2) the asymmetric deformations, especially in the fully closed
      configuration, justify the use of cyclic symmetry; (3) adopting the fully-open
      position as an initial/reference configuration has the advantage of completely
      bypassing any complications arising from the need to assume the size and shape of
      the contact area in the coaptation regions of the leaflets that is necessary when
      the alternative, commonly-used, approach of selecting the fully-closed position
      is used as a reference; and (4) with proper treatments for both material
      anisotropy and tissue-to-tissue contact, the overall BHV model provide realistic
      results in conformity with the ex vivo/in vitro experiments.

PMID- 22483758
TI  - A multi-tissue mass-spring model for computer assisted breast surgery.
AB  - The aim of this work was to develop and validate a 3D female breast deformation
      model for computer assisted breast surgery. Magnetic resonance (MR) image data of
      a patient undergoing breast biopsy, were acquired using two different protocols
      with the patient in prone position: (i) uncompressed breast and (ii) compressed
      breast, with lateral single breast compression, realized with a movable slab. The
      acquired images were then segmented using a semi-automatic procedure and from the
      extracted volumes of interest tetrahedral meshes representing skin, fat and
      mammary glands were generated. Tissue deformation was ruled by a mass-spring
      model: first, an iterative approximation algorithm was implemented to estimate
      the spring's rest length and stiffness, accounting for gravity force; then the
      resulting parameters were used to deform the uncompressed breast model in order
      to reach the real compressed one (ground truth). Results showed that gravity
      force applied to the mesh was properly compensated by the internal elastic
      forces, leading to a distance between the deformed mesh and the reference data of
      0.036+/-0.092 mm (median+/-inter quartile range). The point to mesh residual
      distance between the deformed mesh and the ground truth was 1.224+/-2.202 mm
      (median+/-inter quartile range). Further investigation on a larger patient
      dataset is required for a more robust confirmation of model accuracy in
      predicting breast deformations.

PMID- 22483759
TI  - An efficient method to limit microglia-dependent effects in astroglial cultures.
AB  - Microglia, the CNS resident macrophages, and astrocytes, the most abundant glial
      cell population, are both implicated in brain pathologies and can exhibit a pro
      inflammatory phenotype. Microglial cells are known to rapidly and strongly react
      to brain insults. They will promote astrocyte activation and may lead to a
      vicious, self-perpetuating cycle of chronic inflammation. To obtain a better
      understanding of the individual role of both cell types, primary cells are
      frequently used in in vitro studies, but the purity of specific cell cultures
      remains rarely investigated. The aim of this study is to determine the effect of
      specific removal of microglial cells on the inflammatory properties of different
      glial cultures. Here, the removal of microglial contamination from mixed glial
      cultures to obtain astrocyte-enriched cultures was achieved using a magnetic cell
      sorting approach. Compared to mixed cultures, we clearly showed that these
      enriched cultures are only weakly activated by pro-inflammatory agents
      (lipopolysaccharide, interferon-gamma or beta-amyloid peptide). This finding was
      confirmed using twice-sorted astrocyte-enriched cultures and microglia-free
      cultures composed of neurosphere-derived astrocytes. Thus, we present evidence
      that the magnitude of the pro-inflammatory response is linked to the percentage
      of microglia in cultures. Due to their high reactivity to various insults or pro
      inflammatory stimuli, microglia-derived effects could be credited to astrocytes
      in mixed glial cultures. Therefore, we highlight the importance of monitoring the
      presence of microglia in glial cultures since they can affect the interpretation
      of the results, especially when inflammatory processes are studied.

PMID- 22483760
TI  - [Comparative results of macular hole surgery with and without internal limiting
      membrane staining with Brilliant Blue G].
AB  - OBJECTIVE: To evaluate the role of Brilliant Blue G (BBG) in macular hole (MH)
      surgery. METHODS: Comparative retrospective study between two groups of 20
      consecutive patients who underwent macular hole surgery. In the first group (G1),
      the inner limiting membrane (ILM) was systematically peeled without staining,
      while in the second group (G2), BBG was consistently utilized. Pre- and
      postoperative logMAR visual acuities (VA) were studied, as well as macular
      optical coherence tomography (OCT) scans to measure MH size, to confirm
      postoperative closure and to evaluate the integrity of the IS/OS junction. Time
      required and difficulty of peeling were compared between the two groups. Minimum
      follow-up was six months. RESULTS: After six months follow-up, the average
      improvement in acuity was 0.56+/-0.48 logMAR for G1, versus 0.60+/-0.44 logMAR
      for G2 (P=0.80). The rate of closure after one surgery was 85% (17/20 patients)
      for G1, versus 95% (19/20 patients) for G2 (P=0.29). Postoperative OCT appearance
      of the IS/OS junction was similar in both groups: intact in 16/20 patients (80%),
      disrupted in 3/20 patients (15%), and indeterminate in 1/20 patients (5%) (P=1).
      The mean duration of peeling in G1 was 270.9+/-27.4 seconds. It was deemed
      difficult in ten eyes and incomplete in two patients, while in the G2 group, the
      mean duration of ILM peeling was 140.8+/-37.6 seconds (P<0.01); it was deemed
      complete and technically easy in all cases. CONCLUSION: The use of BBG was
      effective in facilitating and accelerating ILM peeling during MH surgery. The
      anatomical and functional results were not statistically better in the group that
      received BBG.

PMID- 22483761
TI  - Efficacy of 0.18% hypotonic sodium hyaluronate ophthalmic solution in the
      treatment of signs and symptoms of dry eye disease.
AB  - BACKGROUND/AIMS: To compare the safety and efficacy of hypotonic 0.18% sodium
      hyaluronate solution (0.18% SH) versus saline and versus 0.3% carbomer for the
      treatment of signs and symptoms of moderate dry eye syndrome. METHODS: A total of
      304 patients were randomized (1:1:1) in this parallel-group, multi-center, phase
      III trial. They were instructed to instill one drop of the allocated product in
      each eye two to four times per day over 84 days. The primary efficacy criterion
      was the change from baseline at Day 28 in symptom frequency score. The
      superiority of 0.18% SH (Vismed((r))) over saline and its non-inferiority versus
      carbomer were statistically tested. RESULTS: At Day 28, there was a statistically
      significant superiority of 0.18% SH over saline in change from baseline for
      subjective symptom frequency score (P=0.0376, primary endpoint) and objective
      fluorescein staining score (P=0.0074, secondary endpoint). 0.18% SH had an
      excellent safety profile over 84 days. A strong trend was observed in favour of
      0.18% SH to cause less blurred vision than carbomer throughout the trial
      (P=0.0798 at Day 28). CONCLUSION: 0.18% SH caused a statistically significant
      improvement in both a subjective endpoint (symptom frequency score) and an
      objective endpoint (fluorescein staining score). 0.18% SH was well tolerated and
      resulted in low incidence of adverse events.

PMID- 22483762
TI  - [Vitreous body aging].
AB  - The most important age-related changes in the vitreous are progressive
      liquefaction and posterior vitreous detachment (PVD). Optical coherence
      tomography enables better in vivo visualization of the vitreoretinal interface
      and has improved our understanding of the process of PVD, but knowledge of the
      biomicroscopic aspects of these vitreous anatomical modifications is required.
      The most common complications include retinal hemorrhage or vitreous hemorrhage,
      retinal breaks, and rhegmatogenous retinal detachment. Patients with symptomatic
      PVD require careful examination.

PMID- 22483763
TI  - Reliability of a self-administered diary of symptoms for assessing the evolution
      of acute bronchitis.

PMID- 22483764
TI  - A forensic DNA profiling system for Northern European brown bears (Ursus arctos).
AB  - A set of 13 dinucleotide STR loci (G1A, G10B, G1D, G10L, MU05, MU09, MU10, MU15,
      MU23, MU26, MU50, MU51, MU59) were selected as candidate markers for a DNA
      forensic profiling system for Northern European brown bear (Ursus arctos). We
      present results from validation of the markers with respect to their sensitivity,
      species specificity and performance (precision, heterozygote balance and stutter
      ratios). All STRs were amplified with 0.6ng template input, and there were no
      false bear genotypes in the cross-species amplification tests. The validation
      experiments showed that stutter ratios and heterozygote balance was more
      pronounced than in the tetranucleotide loci used in human forensics. The elevated
      ratios of stutter and heterozygote balance at the loci validated indicate that
      these dinucleotide STRs are not well suited for interpretation of individual
      genotypes in mixtures. Based on the results from the experimental validations we
      discuss the challenges related to genotyping dinucleotide STRs in single source
      samples. Sequence studies of common alleles showed that, in general, the size
      variation of alleles corresponded with the variation in number of repeats. The
      samples characterized by sequence analysis may serve as standard DNA samples for
      inter laboratory calibration. A total of 479 individuals from eight Northern
      European brown bear populations were analyzed in the 13 candidate STRs. Locus
      MU26 was excluded as a putative forensic marker after revealing large deviations
      from expected heterozygosity likely to be caused by null-alleles at this locus.
      The remaining STRs did not reveal significant deviations from Hardy-Weinberg
      equilibrium expectations except for loci G10B and MU10 that showed significant
      deviations in one population each, respectively. There were 9 pairwise locus
      comparisons that showed significant deviation from linkage equilibrium in one or
      two out of the eight populations. Substantial genetic differentiation was
      detected in some of the pairwise population comparisons and the average estimate
      of population substructure (F(ST)) was 0.09. The average estimate of inbreeding
      (F(IS)) was 0.005. Accounting for population substructure and inbreeding the
      total average probability of identity in each of the eight populations was lower
      than 1.1*10(-9) and the total average probability of sibling identity was lower
      than 1.3*10(-4). The magnitude of these measurements indicates that if applying
      these twelve STRs in a DNA profiling system this would provide individual
      specific evidence.

PMID- 22483765
TI  - [Development of new indications for old products: difficulties and search for
      solutions].

PMID- 22483766
TI  - [Development of synergies and partnerships on rare diseases: model of a
      scientific cooperation foundation].

PMID- 22483767
TI  - [Presenting a research project on rare diseases to industrial companies].

PMID- 22483768
TI  - [Inaugural conference: Progress made in the Second National Plan for Rare
      Diseases].

PMID- 22483769
TI  - [Precompetitive tools and resources for leveraging R&D in Europe].

PMID- 22483770
TI  - [The stakes of pre- and post-market authorization development and clinical
      assessment].

PMID- 22483771
TI  - [Non-medicinal care of rare diseases].

PMID- 22483772
TI  - [Introduction and welcome message].

PMID- 22483773
TI  - [Methodology and management of clinical trials with small number of patients for
      rare diseases].

PMID- 22483774
TI  - [Possible framework and best practices in the future for prescriptions outside
      market authorization indications for rare diseases?].

PMID- 22483775
TI  - Acute promyelocytic leukaemia associated Factor XIII deficiency presenting as
      retro-bulbar haematoma.

PMID- 22483776
TI  - Challenges in the laboratory analyses of bleeding disorders.
AB  - Standard coagulation assays such as the activated partial thromboplastin time and
      prothrombin time are sufficient to detect deficiencies in coagulation factors
      contributing to the intrinsic and extrinsic pathways, respectively. Deficiencies
      in factors VIII and IX can also be detected by one-stage and two-stage clotting
      assays. While these assays are instrumental in assessing the initiation of clot
      formation, sufficient formation of a clot is a continuous process that may be
      better studied by the use of a global hemostasis assay. Several global assays are
      currently being studied, including the thrombin generation assay,
      thromboelastography, clot waveform analysis, clot formation and lysis (CloFAL)
      assay, euglobulin clot lysis assay, thromboplastin generation assays and
      simultaneous thrombin and plasmin generation assays. This review will concentrate
      on the thrombin generation test, thromboelastography, the activated partial
      thromboplastin time waveform analysis and the CloFAL which measure the production
      of thrombin, as well as the kinetics of clot formation. As such, these global
      assays can provide greater insight into deficiencies in the mechanisms mediating
      hemostasis and fibrinolysis in patients with hemophilia, other bleeding disorders
      or even thrombophilia. These assays have been shown to be clinically relevant for
      assessing the response to treatment with bypassing agents (recombinant activated
      FVII and plasma-derived prothrombin complex concentrate) used for the hemostatic
      control of acute bleeding in patients with congenital hemophilia A/B. The
      limitations of standard coagulation assays and the use of global hemostasis
      assays to assess bleeding disorders and the clinical efficacy of bypassing agents
      will be discussed in detail.

PMID- 22483777
TI  - Amurensin G, a novel SIRT1 inhibitor, sensitizes TRAIL-resistant human leukemic
      K562 cells to TRAIL-induced apoptosis.
AB  - Many types of cancer cells remain resistant towards TRAIL-induced cytotoxicity by
      the blockade of apoptotic signaling cascades. Thus, sensitizers are needed to
      enhance the effect of TRAIL-based cancer therapies. Although synergistic tumor
      cell death has been reported when various HDAC inhibitors were administered with
      TRAIL in a variety of human cancers, the effect of inhibitors of Class III HDAC
      such as SIRT1 have not been reported. We reported here for the first time that
      inhibition of SIRT1 augmented the cytotoxic and apoptotic effects of TRAIL on
      human leukemic K562 cells. Knockdown of SIRT1 or treatment with amurensin G, a
      potent new SIRT1 inhibitor, up-regulated the levels of DR5 and c-Myc and down
      regulated the level of c-FLIP(L/S). Furthermore, knockdown of SIRT1 or treatment
      with amurensin G augmented the molecular responses to TRAIL, including activation
      of caspase-8, -9 and -3, PARP cleavage, up-regulation of Bax, and down-regulation
      of Bcl-2. Amurensin G-enhanced TRAIL-induced apoptosis was abrogated by caspase
      inhibitor Z-VAD-FMK. These findings suggest that the suppression of SIRT1 with
      siRNA or amurensin G sensitize the TRAIL-resistant K562 cell to TRAIL-induced
      apoptosis, possibly by the up-regulation of c-Myc and DR5 surface expression and
      the down-regulations of c-FLIP and Mcl-1. In addition, amurensin G, a potent new
      SIRT1 inhibitor, would be used as a sensitizer of TRAIL in TRAIL-resistant
      leukemic cells.

PMID- 22483778
TI  - Effects of dehydration on the viscoelastic properties of vocal folds in large
      deformations.
AB  - Dehydration may alter vocal fold viscoelastic properties, thereby hampering
      phonation. The effects of water loss induced by an osmotic pressure potential on
      vocal fold tissue viscoelastic properties were investigated. Porcine vocal folds
      were dehydrated by immersion in a hypertonic solution, and quasi-static and low
      frequency dynamic traction tests were performed for elongations of up to 50%.
      Digital image correlation was used to determine local strains from surface
      deformations. The elastic modulus and the loss factor were then determined for
      normal and dehydrated tissues. An eight-chain hyperelastic model was used to
      describe the observed nonlinear stress-stretch behavior. Contrary to the
      expectations, the mass history indicated that the tissue absorbed water during
      cyclic extension when submerged in a hypertonic solution. During loading history,
      the elastic modulus was increased for dehydrated tissues as a function of strain.
      The response of dehydrated tissues was much less affected when the load was
      released. This observation suggests that hydration should be considered in
      micromechanical models of the vocal folds. The internal hysteresis, which is
      often linked to phonation effort, increased significantly with water loss. The
      effects of dehydration on the viscoelastic properties of vocal fold tissue were
      quantified in a systematic way. A better understanding of the role of hydration
      on the mechanical properties of vocal fold tissue may help to establish objective
      dehydration and phonotrauma criteria.

PMID- 22483779
TI  - Application of total care time and payment per unit time model for physician
      reimbursement for common general surgery operations.
AB  - BACKGROUND: The relative value unit system relies on subjective measures of
      physician input in the care of patients. A payment per unit time model
      incorporates surgeon reimbursement to the total care time spent in the operating
      room, postoperative in-house, and clinic time to define payment per unit time. We
      aimed to compare common general surgery operations by using the total care time
      and payment per unit time method in order to demonstrate a more objective
      measurement for physician reimbursement. STUDY DESIGN: Average total physician
      payment per case was obtained for 5 outpatient operations and 4 inpatient
      operations in general surgery. Total care time was defined as the sum of
      operative time, 30 minutes per hospital day, and 30 minutes per office visit for
      each operation. Payment per unit time was calculated by dividing the physician
      reimbursement per case by the total care time. RESULTS: Total care time,
      physician payment per case, and payment per unit time for each type of operation
      demonstrated that an average payment per time spent for inpatient operations was
      $455.73 and slightly more at $467.51 for outpatient operations. Partial colectomy
      with primary anastomosis had the longest total care time (8.98 hours) and the
      least payment per unit time ($188.52). Laparoscopic gastric bypass had the
      highest payment per time ($707.30). CONCLUSIONS: The total care time and payment
      per unit time method can be used as an adjunct to compare reimbursement among
      different operations on an institutional level as well as on a national level.
      Although many operations have similar payment trends based on time spent by the
      surgeon, payment differences using this methodology are seen and may be in need
      of further review.

PMID- 22483780
TI  - A novel HIV-1 reporter virus with a membrane-bound Gaussia princeps luciferase.
AB  - HIV-1 reporter viruses are a critical tool for investigating HIV-1 infection. By
      having a reporter gene incorporated into the HIV-1 genome, the expressed reporter
      protein acts as a specific tag, thus enabling specific detection of HIV-1
      infected cells. Currently existing HIV-1 reporter viruses utilize reporters for
      the detection of HIV-1 infected cells by a single assay. A reporter virus
      enabling the detection of viral particles as well as HIV-1 infected cells by two
      assays can be more versatile for many applications. In this report, a novel
      reporter HIV-1 was generated by introducing a membrane-anchored form of the
      Gaussia princeps luciferase gene (mGluc) upstream of the nef gene in the HIV
      1(NL4-3) genome using a picornaviral 2A-like sequence. The resulting HIV-1(NL4
      3mGluc) virus expresses G. princeps luciferase efficiently on viral membrane and
      the cell surface of infected human T cell lines and primary peripheral blood
      mononuclear cells. This HIV-1 reporter is replication competent and the reporter
      gene mGluc is expressed during multiple rounds of infection. Importantly, viral
      particles can be detected by bioluminescence and infected cells can be detected
      simultaneously by bioluminescence and flow cytometric assays. With the
      versatility of two sensitive detection methods, this novel luciferase reporter
      has many applications such as cell-based screening for anti-HIV-1 agents or
      studies of HIV-1 pathogenicity.

PMID- 22483781
TI  - Manual testing for ankle instability.
AB  - AIM: To assess inter-rater reliability of ankle manual tests. We also correlated
      the manual tests with the Cumberland Ankle Instability Tool (CAIT). METHOD: One
      ankle from each of 60 participants was assessed using four different manual tests
      (anterior drawer in supine and crook lying, talar tilt, inversion tilt). Three
      different raters, varying in experience, tested each participant. The CAIT
      questionnaire was also administered. The study received ethics approval from the
      University of Sydney Human Research Ethics Committee. Intraclass correlation
      coefficients (ICC), standard error of the mean (SEM) and percent close agreement
      (PCA) were used to determine reliability of the four tests. Pearson's correlation
      coefficients were used to determine relationships between the manual tests and
      CAIT scores. RESULTS: Inter-rater reliability for the four manual tests was poor
      regardless of therapist's experience (ICC([1,1]) -0.12 to 0.33; SEM 0.93-1.69).
      Correlations between the CAIT and manual tests were also low varying between r = 
      0.12 and -0.42. CONCLUSIONS: Inter-rater reliability was poor for manual tests of
      ankle stability. Reliability may be improved by using a grading scale with fewer
      intervals. The CAIT scores and manual tests correlated poorly, potentially
      reflecting the variety of conditions leading to ankle instability.

PMID- 22483782
TI  - Clinicoradiologic characteristics of patients with lung adenocarcinoma harboring
      EML4-ALK fusion oncogene.
AB  - INTRODUCTION: The fusion oncogene of echinoderm microtubule-associated protein
      like 4 (EML4) and anaplastic lymphoma kinase (ALK) defines a new molecular subset
      of non-small-cell lung cancer. We explored the EML4-ALK gene in a relatively
      large cohort and reviewed the clinicoradiologic background of the patients.
      METHODS: We studied 720 patients with lung adenocarcinoma. The
      clinicopathological characteristics of each patient were compared among the
      subgroups stratified by the EML4-ALK gene status. For radiographic evaluation, we
      scored the proportion of the ground-glass opacity (GGO) component and calculated
      the tumor disappearance rate (TDR) in each tumor in the cohort of 168 patients
      that were extracted by using a case-matching procedure. RESULTS: Twenty-eight
      (3.9%) patients harbored the EML4-ALK gene. Younger age (p=0.001), no or light
      history of smoking (p=0.05) and normal serum carcinoembryonic antigen (CEA) level
      (p=0.04) were characteristics of the patients with EML4-ALK. No significant
      difference was observed for overall and disease free survival between the two
      groups. All but one tumor in the EML4-ALK-positive group exhibited no GGO,
      whereas half of the tumors (69/140 patients) in the EML4-ALK-negative group
      exhibited some GGO (p=0.0004). The mean TDRs were 0.33 and 0.54, respectively,
      which was significantly lower in the positive group (p=0.0006). CONCLUSIONS: We
      identified younger age, no or light history of smoking, and normal serum CEA as
      clinical features of patients with EML4-ALK-positive lung adenocarcinoma. In
      addition, EML4-ALK-positive tumors exhibited a solid pattern on CT. These
      features may be of value in predicting for patient selection for ALK inhibition
      therapy in the absence of genetic screening.

PMID- 22483783
TI  - The gefitinib long-term responder (LTR)--a cancer stem-like cell story? Insights
      from molecular analyses of German long-term responders treated in the IRESSA
      expanded access program (EAP).
AB  - BACKGROUND: In selected patients with advanced non-small cell lung cancer (NSCLC)
      the EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor (TKI)
      gefitinib (IRESSA) shows response rates of >= 70% and a significant prolongation
      of progression free survival (PFS). However, cogent biomarkers predicting long
      term response to EGFR-TKIs are yet lacking. Cancer stem-like cells (CSC) are
      thought to play a pivotal role in tumor regeneration and appear to be influenced
      by the EGFR-pathway. This makes them a promising candidate for predicting long
      term response to EGFR-TKIs. MATERIALS AND METHODS: We analyzed pre-therapeutic
      tissue specimens of a rare and specific subset of previously treated German
      patients with advanced NSCLC who experienced >= 3 year response to gefitinib
      within the International IRESSA EAP. 11/20 identified long-term responders (LTRs)
      had appropriate tissue specimens available. Those were analyzed for EGFR and k
      ras (Kirsten rat sarcoma) mutations, EGFR and c-met (met proto-oncogene)
      amplifications and protein expression of EGFR, E-cadherin/vimentin and the CSC
      antigens CD133 and BCRP1 (breast cancer resistance protein 1). The results were
      compared to primary resistant patients (RPs) and intermediate responders (IRs)
      showing a median response of 8.6 months. RESULTS: Each group consisted of 6 women
      and 5 men, with 1 squamous cell carcinoma (SCC) and 10 adenocarcinoma (AC). Along
      the LTRs, all but the SCC had EGFR mutations, whereas the RPs had no EGFR, but k
      ras mutations in 5/11 cases. 8/11 IRs had EGFR and 3/11 k-ras mutations, of which
      2 occurred concomitantly. One patient of each group had an EGFR and/or c-met
      amplification. EGFR and E-cadherin/vimentin expression was not different between
      the groups, whereas CD133 was expressed only in 4/10 LTRs and BCRP1 predominantly
      in responders. The LTRs showed a substantially longer mean PFS to previous
      therapies, a substantially lower number of metastatic sites and almost
      exclusively pulmonary or pleural metastasis. CONCLUSION: LTRs display established
      properties of EGFR-TKI responders. Antigens characterizing CSC might identify a
      fraction of LTRs and matter of interest for further evaluation.

PMID- 22483784
TI  - [Epidemiology of extended spectrum beta-lactamases (ESBL) Enterobacteriaceae in a
      General Hospital, South of France, 1999-2007].
AB  - PURPOSE OF THE STUDY: The global epidemiology of extended spectrum betalactamases
      (ESBL) producing Enterobacteriaceae has evolved in recent years with the
      emergence of a new type of ESBL: CTX-M, mainly in Escherichia coli. These CTX-M
      type producing Enterobacteriaceae are responsible for both nosocomial and, more
      recently, community infections, including urinary tract infections. The aim of
      our work is to study ESBL producing Enterobacteriaceae evolution between 1999 and
      2007 in the population from the Centre Hospitalier du Pays-d'Aix (CHPA), a
      general hospital from South of France. PATIENTS AND METHODS: ESBL producing
      strains of Enterobacteriaceae isolated in odd years between 1999 and 2007 from
      clinical isolates of all origins have been phenotypically identified and their
      ESBL genotyped. Molecular and epidemiological data from our hospital health-care
      associated infection committee were analyzed. RESULTS: Two hundred and sixty-two
      ESBL producing isolates were studied. Within ESBL producing Enterobacteriaceae,
      Enterobacter aerogenes was predominant in 1999 (48.7% of isolates), and decreased
      to 18.8% of isolates in 2007. On the other hand, E. coli, which represented 10.5%
      of ESBL isolates in 1999, grew up to 37.5% of the isolates in 2007. ESBL
      prevalence in E. coli increased during this period from 0.3 to 2.5%.
      Simultaneously, ESBL, predominantly TEM-24 in 1999, were replaced by CTX-M in
      2007, among which CTX-M-15 is predominant (88% of CTX-M). CONCLUSION: Our study
      confirms a major change in ESBL epidemiology in CHPA, with the emergence of CTX-M
      type ESBL, mainly CTX-M 15, and an increase of ESBL prevalence in E. coli.

PMID- 22483785
TI  - Exercise protects against high-fat diet-induced hypothalamic inflammation.
AB  - Hypothalamic inflammation is a potentially important process in the pathogenesis
      of high-fat diet-induced metabolic disorders that has recently received
      significant attention. Microglia are macrophage-like cells of the central nervous
      system which are activated by pro-inflammatory signals causing local production
      of specific interleukins and cytokines, and these in turn may further promote
      systemic metabolic disease. Whether or how this microglial activation can be
      averted or reversed is unknown. Since running exercise improves systemic
      metabolic health and has been found to promote neuronal survival as well as the
      recovery of brain functions after injury, we hypothesized that regular treadmill
      running may blunt the effect of western diet on hypothalamic inflammation. Using
      low-density lipoprotein receptor deficient (l dlr-/-) mice to better reflect
      human lipid metabolism, we first confirmed that microglial activation in the
      hypothalamus is severely increased upon exposure to a high-fat, or "western",
      diet. Moderate, but regular, treadmill running exercise markedly decreased
      hypothalamic inflammation in these mice. Furthermore, the observed decline in
      microglial activation was associated with an improvement of glucose tolerance.
      Our findings support the hypothesis that hypothalamic inflammation can be
      reversed by exercise and suggest that interventions to avert or reverse neuronal
      damage may offer relevant potential in obesity treatment and prevention.

PMID- 22483786
TI  - An "I" on cardiac hypertrophic remodelling: imidazoline receptors and heart
      disease.
AB  - The centrally-acting sympatholytic imidazoline compound, moxonidine, prevents the
      development of left ventricular hypertrophy and attenuates maladaptive
      proliferative signalling as well as downstream apoptotic pathways in
      spontaneously hypertensive rat and cardiomyopathic hamster hearts. The actions
      are selectively mediated by imidazoline type-1 receptor (I(1)-receptor, also
      named nischarin), nonadrenergic neurotransmitter receptors mainly found in the
      brainstem medulla. We identified cardiac I(1)-receptors/nischarin and showed that
      they are upregulated in cardiovascular disorders, and are functional without the
      central nervous system's contribution. Molecular characterization revealed that
      I(1)-receptor/nischarin has a unique structure with multifunctional domains
      allowing it to perform a number of cell signalling roles as a scaffolding
      protein. Nischarin has been associated with integrin alpha5 and inhibition of
      Rac1 and was shown to interact with insulin receptor substrates. However, very
      little is known about cardiac I(1)-receptor/nischarin and its role(s) in normal
      physiology and pathophysiology, specifically in cardiac remodelling. Our studies
      have shown that I(1)-receptor is expressed in cardiac fibroblasts and myocytes
      and that in vitro I(1)-receptor activation inhibits norepinephrine-induced
      cardiomyocyte apoptosis and fibroblast proliferation, through differential
      effects on mitogen-activated protein kinases and Akt. Accordingly, apart from
      centrally-mediated sympatholytic function, I(1)-receptor in the heart may control
      cell growth and death. I(1)-receptor may be implicated in cardiac remodelling and
      dysfunction, through the inhibition of apoptotic pathways and/or activation of
      survival pathways, in a cell-specific manner. Identification of the
      cardioprotective mechanisms of cardiac I(1)-receptor could result in specifically
      tailored cell/gene-driven I(1)-receptor treatments, and/or treatments that target
      cardiac I(1)-receptor, which could eventually be important for patients with
      hypertrophic heart disease.

PMID- 22483787
TI  - Bridging the gap: innovative knowledge translation and the Canadian hypertension
      education program.

PMID- 22483788
TI  - Key players in major and bipolar depression--a retrospective analysis of in vivo
      imaging studies.
AB  - In the present study, we evaluated the contribution of the individual synaptic
      constituents of all assessed neurotransmitter systems by subjecting all available
      in vivo imaging studies on patients with unipolar major depressive disorder (MDD)
      and bipolar depression (BD) to a retrospective analysis. In acute MDD, findings
      revealed significant increases of prefrontal and frontal DA synthesis, decreases
      of thalamic and midbrain SERT, increases of insular SERT, decreases of midbrain 5
      HT(1A) receptors and decreases of prefrontal, frontal, occipital and cingulate 5
      HT(2A) receptors, whereas, in remission, decreases of striatal D2 receptors,
      midbrain SERT, frontal, parietal, temporal, occipital and cingulate 5-HT(1A)
      receptors and parietal 5-HT(2A) receptors were observed. In BD, findings
      indicated a trend towards increased striatal D2 receptors in depression and
      mania, decreased striatal DA synthesis in remission and decreased frontal D1
      receptors in all three conditions. Additionally, there is some evidence that
      ventrostriatal and hippocampal SERT may be decreased in depression, whereas in
      remission and mania elevations of thalamic and midbrain SERT, respectively, were
      observed. Moreover, in depression, limbic 5-HT(1A) receptors were elevated,
      whereas in mania a decrease of both cortical and limbic 5-HT(2A) receptor binding
      was observed. Furthermore, in depression, prefrontal, frontal, occipital and
      cingulate M2 receptor binding was found to be reduced. From this, a complex
      pattern of dysregulations within and between neurotransmitter systems may be
      derived, which is likely to be causally linked not only with the subtype and
      duration of disease but also with the predominance of individual symptoms and
      with the kind and duration of pharmacological treatment(s).

PMID- 22483789
TI  - Asymmetry in antennal contacts during trophallaxis in ants.
AB  - Behavioural and brain left-right asymmetries are a common feature among the
      animal kingdom. Lateralization often manifests itself at the population-level
      with most individuals showing the same direction of lateral bias. Theoretical
      model based on evolutionary stable strategy predicts that lateralization at the
      population-level is more likely to characterize social rather than solitary
      species. Empirical data supporting this hypothesis has been recently obtained in
      Hymenoptera showing that eusocial honeybees present an asymmetrical use of the
      antennae: the right antenna is involved in olfactory learning and present more
      olfactory receptors. However, no evidences about the role of antennal asymmetries
      in social interactions have been provided so far. Highly social ant species
      belonging to Formica rufa group are a good model for investigating natural
      communication because they are able to pass exact information to their nest
      mates. We applied the "binary tree" experimental paradigm, which allowed us to
      observe different types of antennal contacts performed by ants out of their nest.
      To examine possible asymmetrical use of the right and left antenna, we focused on
      "feeding" (the simplest) contacts where a "donor" ant is exchanging food with a
      "receiver" ant through trophallaxis. We observed a population-level asymmetry,
      with the "receiver" ant using the right antenna significantly more often than the
      left antenna. This study provides the first evidence of lateralization in
      antennal contacts in ants, and seems to support the hypothesis of mathematical
      models on the evolution of lateralization suggesting that the alignment of
      lateralization at the population-level matters in social interactions.

PMID- 22483790
TI  - Load-dependent posterior-anterior shift in aging in complex visual selective
      attention situations.
AB  - The cognitive reserve hypothesis proposes that the brain actively attempts to
      cope with age-related changes by using pre-existing cognitive networks (neural
      reserve) or enlisting compensatory processes (neural compensation). In a context
      of visual selective attention, the current study compared task-related activation
      with BOLD fMRI signals in younger (N=16) and older (N=16) adults using a letter
      name-matching task with two attentional load levels. In the low-load condition,
      the target letter might share the same identity (e.g., a/A) with one of two
      probes in the display, while in the high-load condition the display included four
      probes. The results suggest that there is an age-related change within the
      frontoparietal network that underlies visual selective attention processing. In
      the low-load condition, the older group needed to recruit more bilateral frontal
      regions to successfully perform the task, while the younger participants
      recruited more bilateral occipital regions, in agreement with the PASA (Posterior
      Anterior Shift in Aging) phenomenon and the neural compensation hypothesis of
      cognitive reserve. In addition, in the high-load condition, we found a load
      dependent posterior-anterior shift in the older participants, which was not
      present in the younger ones, involving the anterior part of the cingulate cortex.
      By showing a load-dependent PASA, our study indicates that the PASA phenomenon is
      supported more by the compensation mechanism (solicited exclusively in older
      participants) than by the reserve.

PMID- 22483791
TI  - Downregulation of N-methyl-D-aspartate receptor zeta1 subunit (GluN1) gene in
      inferior colliculus with aging.
AB  - Presbycusis is the impairment of auditory function associated with aging, which
      stems from peripheral cochlear lesions and degeneration of the central auditory
      process. The effect of age-induced peripheral hearing loss on the central
      auditory process is not fully understood. C57Bl/6 (C57) mice present accelerated
      peripheral hearing loss, which is well developed by middle-age and mimics the
      human presbycusis pattern. The aim of this study was to elucidate the molecular
      effects of peripheral hearing loss in the inferior colliculus (IC) with age
      between young and middle-aged C57 mice using cDNA microarray. Glutamate receptor
      ionotropic NMDA zeta1 (GluN1) exhibited the greatest decrease in the middle-aged
      group as determined using cDNA microarray and by further assessment using real
      time PCR (qPCR). Histological assessment with in situ hybridization of GluN1
      showed significantly decreased expression in all IC subdivisions of the middle
      aged group. GluN1 is a receptor for excitatory neurotransmission, and significant
      downregulation of this gene may be subsequent to the decline of afferent input
      from the cochlea in aging C57 mice. Consequently, using the combination of
      microarray, qPCR, and in situ hybridization, we showed that the decline of GluN1
      in the IC of aging animals might have a key role in the pathogenesis of
      presbycusis.

PMID- 22483792
TI  - Role of the NMDA receptor and iron on free radical production and brain damage
      following transient middle cerebral artery occlusion.
AB  - Excess activation of ionotropic glutamate receptors and iron is believed to
      contribute to free radical production and neuronal death following hypoxic
      ischemia. We examined the possibility that both NMDA receptor activation and iron
      overload determine spatial and temporal patterns of free radical production after
      transient middle cerebral artery occlusion (tMCAO) in male Sprague-Dawley rats.
      Mitochondrial free radical (MFR) levels were maximally increased in neurons in
      the core at 1 h and 24 h after tMCAO. Early MFR production was blocked by
      administration of MK-801, an NMDA receptor antagonist, but not deferoxamine, an
      iron chelator. Neither MK-801 nor deferoxamine attenuated late MFR production in
      the core. Increased MFRs were observed in penumbral neurons within 6 h and
      gradually increased over 24 h after tMCAO. Slowly-evolving MFRs in the core and
      penumbra were accompanied by iron overload. Deferoxamine blocked iron overload
      but reduced MFR production only in the penumbra. Combined MK-801/deferoxamine
      reduced late MFR production in both core and penumbra in an additive manner.
      Combination therapy significantly ameliorated infarction compared with
      monotherapy. These findings suggest that the NMDA receptor activation and iron
      overload mediate late MFR production and infarction after tMCAO.

PMID- 22483793
TI  - A new method for the measurement of lysosomal acid lipase in dried blood spots
      using the inhibitor Lalistat 2.
AB  - BACKGROUND: Cholesterol ester storage disease (CESD) and Wolman Disease (WD) are
      due to deficiency of lysosomal acid lipase (LAL). A new method is described for
      the measurement of LAL in dried blood spots (DBS) using Lalistat 2 an inhibitor
      of LAL. METHODS: LAL activity in DBS extracts was measured using the substrate 4
      methylumbelliferyl palmitate. LAL activity was determined by measuring total
      lipase activity and lipase activity in the presence of Lalistat 2. The
      specificity of Lalistat 2 was investigated using human recombinant LAL (hrLAL)
      and human pancreatic lipase (hPL). RESULTS: Lalistat 2 inhibited hrLAL with 1%
      residual activity at 1 MUM inhibitor but had no effect on hPL up to 10 MUM. LAL
      activity in DBS samples obtained from normal controls (n=140) was 0.50-2.30
      nmol/punch/h and in patients with CESD was <0.03 nmol/punch/h (n=11). Activity in
      carriers showed intermediate activity: 0.15-0.40 nmol/punch/h (n=15).
      CONCLUSIONS: Measurement of LAL using DBS is made difficult by the presence of
      other lipases in whole blood. Lalistat 2 is a specific inhibitor of LAL which
      allows the determination of LAL in DBS. Results show the method differentiates
      clearly between normal controls, carriers and affected cases.

PMID- 22483794
TI  - Comparison of gel-based methods for the detection of cerebrospinal fluid
      rhinorrhea.
AB  - Cerebrospinal fluid (CSF) rhinorrhea is a serious condition that may result in
      severe complications. Various laboratory tests, relying on the detection of CSF
      specific proteins in nasal secretions, have been developed but diagnosis remains
      challenging. The aim of this study was to evaluate two new methods targeting
      either beta2-transferrin or beta-trace-protein. Rhinorrhea samples from patients
      suspected of CSF leakage (n=36) were analyzed using two-dimensional gel
      electrophoresis (2-DE) for CSF rhinorrhea diagnosis. Twelve patients with
      rhinorrhea strongly suggestive of a CSF leak also underwent a fluorescein test.
      The same cohort was retrospectively analyzed with a beta-trace protein immunoblot
      developed in-house (n=36) and a new commercial beta2-transferrin immunofixation
      assay (Sebia, Evry, France) (n=33). 2-DE was positive in 9 patients suffering
      from rhinorrhea following skull base fracture (n=3), post-surgery (n=4), or
      spontaneously (n=2). The 27 remaining cases were negative. These results were
      confirmed by the beta-trace protein immunoblot and beta2-transferrin
      immunofixation tests, except for one sample found negative with 2-DE but positive
      with the two other assays. Results from the three analytical methods were
      concordant with fluorescein tests. Beta-trace protein immunoblot and beta2
      transferrin immunofixation assays are fast and reliable methods that allow
      detecting CSF leakage in nasal fluid with high sensitivity and specificity.

PMID- 22483795
TI  - [Pregnancy and acute pulmonary embolism: a case report].
AB  - We describe the case of a 37-year-old pregnant woman who presented at 29 weeks of
      gestation with syncope and shortness of breath caused by pulmonary embolism. Due
      to persistent hypotension thrombolytic therapy with tenecteplase was administered
      and the clinical and hemodynamic response was excellent, with no maternal or
      fetal hemorrhagic complications. The clinical presentation of pulmonary embolism
      is sometimes camouflaged by the physiological changes that occur in pregnancy and
      diagnosis is often delayed by reluctance to expose the fetus to ionizing
      radiation. Systemic thrombolysis is considered a high-risk treatment in pregnancy
      and very few women have received it. However the complication rates of
      thrombolytic therapy are acceptable in the light of the underlying disease.

PMID- 22483796
TI  - [High-risk pulmonary embolism with right heart thrombi].

PMID- 22483797
TI  - [Databases in cardiology: from intervention to information].

PMID- 22483798
TI  - Enniatin B-induced cell death and inflammatory responses in RAW 267.4 murine
      macrophages.
AB  - The mycotoxin enniatin B (EnnB) is predominantly produced by species of the
      Fusarium genera, and often found in grain. The cytotoxic effect of EnnB has been
      suggested to be related to its ability to form ionophores in cell membranes. The
      present study examines the effects of EnnB on cell death, differentiation,
      proliferation and pro-inflammatory responses in the murine monocyte-macrophage
      cell line RAW 264.7. Exposure to EnnB for 24 h caused an accumulation of cells in
      the G0/G1-phase with a corresponding decrease in cyclin D1. This cell cycle
      arrest was possibly also linked to the reduced cellular ability to capture and
      internalize receptors as illustrated by the lipid marker ganglioside GM1. EnnB
      also increased the number of apoptotic, early apoptotic and necrotic cells, as
      well as cells with elongated spindle-like morphology. The Neutral Red assay
      indicated that EnnB induced lysosomal damage; supported by transmission electron
      microscopy (TEM) showing accumulation of lipids inside the lysosomes forming
      lamellar structures/myelin bodies. Enhanced levels of activated caspase-1 were
      observed after EnnB exposure and the caspase-1 specific inhibitor ZYVAD-FMK
      reduced EnnB-induced apoptosis. Moreover, EnnB increased the release of
      interleukin-1 beta (IL-1beta) in cells primed with lipopolysaccharide (LPS), and
      this response was reduced by both ZYVAD-FMK and the cathepsin B inhibitor CA
      074Me. In conclusion, EnnB was found to induce cell cycle arrest, cell death and
      inflammation. Caspase-1 appeared to be involved in the apoptosis and release of
      IL-1beta and possibly activation of the inflammasome through lysosomal damage and
      leakage of cathepsin B.

PMID- 22483799
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and
      alters sex steroid hormone secretion without affecting growth of mouse antral
      follicles in vitro.
AB  - The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) is an ovarian toxicant. These studies were designed to characterize the
      actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in
      vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads
      to decreased sex hormone production/secretion by antral follicles as well as
      decreased growth of antral follicles in vitro. Since TCDD acts through binding to
      the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an
      important factor in ovarian function, we also conducted experiments to confirm
      the presence and activation of the AHR in our tissue culture system. To do so, we
      exposed mouse antral follicles for 96 h to a series of TCDD doses previously
      shown to have effects on ovarian tissues and cells in culture, which also
      encompass environmentally relevant and pharmacological exposures (0.1-100 nM), to
      determine a dose response for TCDD in our culture system for growth, hormone
      production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD
      decreases progesterone, androstenedione, testosterone, and estradiol levels in a
      non-monotonic dose response manner without altering growth of antral follicles.
      The addition of pregnenolone substrate (10 MUM) restores hormone levels to
      control levels. Additionally, Cyp1b1 levels were increased by 3-4 fold regardless
      of the dose of TCDD exposure, evidence of AHR activation. Overall, these data
      indicate that TCDD may act prior to pregnenolone formation and through AHR
      transcriptional control of Cyp1b1, leading to decreased hormone levels without
      affecting growth of antral follicles.

PMID- 22483800
TI  - F-actin is an evolutionarily conserved damage-associated molecular pattern
      recognized by DNGR-1, a receptor for dead cells.
AB  - Sterile inflammation can be initiated by innate immune recognition of markers of
      tissue injury termed damage-associated molecular patterns (DAMPs). DAMP
      recognition by dendritic cells (DCs) has also been postulated to lead to T cell
      responses to foreign antigens in tumors or allografts. Many DAMPs represent
      intracellular contents that are released upon cell damage, notably after
      necrosis. In this regard, we have previously described DNGR-1 (CLEC9A) as a DC
      restricted receptor specific for an unidentified DAMP that is exposed by necrotic
      cells and is necessary for efficient priming of cytotoxic T cells against dead
      cell-associated antigens. Here, we have shown that the DNGR-1 ligand is preserved
      from yeast to man and corresponds to the F-actin component of the cellular
      cytoskeleton. The identification of F-actin as a DNGR-1 ligand suggests that
      cytoskeletal exposure is a universal sign of cell damage that can be targeted by
      the innate immune system to initiate immunity.

PMID- 22483801
TI  - Structures of the HIN domain:DNA complexes reveal ligand binding and activation
      mechanisms of the AIM2 inflammasome and IFI16 receptor.
AB  - Recognition of DNA by the innate immune system is central to antiviral and
      antibacterial defenses, as well as an important contributor to autoimmune
      diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon
      inducible protein 16) have been identified as DNA receptors that induce
      inflammasome formation and interferon production, respectively. Here we present
      the crystal structures of their HIN domains in complex with double-stranded (ds)
      DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic
      attraction between the positively charged HIN domain residues and the dsDNA sugar
      phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains
      in an autoinhibited state is liberated by DNA binding, which may facilitate the
      assembly of inflammasomes along the DNA staircase. These findings provide
      mechanistic insights into dsDNA as the activation trigger and oligomerization
      platform for the assembly of large innate signaling complexes such as the
      inflammasomes.

PMID- 22483802
TI  - The dendritic cell receptor Clec9A binds damaged cells via exposed actin
      filaments.
AB  - The immune system must distinguish viable cells from cells damaged by physical
      and infective processes. The damaged cell-recognition molecule Clec9A is
      expressed on the surface of the mouse and human dendritic cell subsets
      specialized for the uptake and processing of material from dead cells. Clec9A
      recognizes a conserved component within nucleated and nonnucleated cells, exposed
      when cell membranes are damaged. We have identified this Clec9A ligand as a
      filamentous form of actin in association with particular actin-binding domains of
      cytoskeletal proteins. We have determined the crystal structure of the human
      CLEC9A C-type lectin domain and propose a functional dimeric structure with
      conserved tryptophans in the ligand recognition site. Mutation of these residues
      ablated CLEC9A binding to damaged cells and to the isolated ligand complexes. We
      propose that Clec9A provides targeted recruitment of the adaptive immune system
      during infection and can also be utilized to enhance immune responses generated
      by vaccines.

PMID- 22483803
TI  - Fungi subvert vaccine T cell priming at the respiratory mucosa by preventing
      chemokine-induced influx of inflammatory monocytes.
AB  - Vaccinologists strive to harness immunity at mucosal sites of pathogen entry. We
      studied respiratory delivery of an attenuated vaccine against Blastomyces
      dermatitidis. We created a T cell receptor transgenic mouse responsive to vaccine
      yeast and found that mucosal vaccination led to poor T cell activation in the
      draining nodes and differentiation in the lung. Mucosal vaccination subverted
      lung T cell priming by inducing matrix metalloproteinase 2 (MMP2), which impaired
      the action of the chemokine CCL7 on egress of CCR2(+) Ly6C(hi) inflammatory
      monocytes from the bone marrow and their recruitment to the lung. Studies in
      Mmp2(-/-) mice, or treatment with MMP inhibitor or rCCL7, restored recruitment of
      Ly6C(hi) monocytes to the lung and CD4(+) T cell priming. Mucosal vaccination
      against fungi and perhaps other respiratory pathogens may require manipulation of
      host MMPs in order to alter chemokine signals needed to recruit Ly6C(hi)
      monocytes and prime T cells at the respiratory mucosa.

PMID- 22483804
TI  - The histone methyltransferase Wbp7 controls macrophage function through GPI
      glycolipid anchor synthesis.
AB  - Histone methyltransferases catalyze site-specific deposition of methyl groups,
      enabling recruitment of transcriptional regulators. In mammals, trimethylation of
      lysine 4 in histone H3, a modification localized at the transcription start sites
      of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1-MLL4) whose
      specific functions are largely unknown. By using a genomic approach, we found
      that in macrophages, MLL4 (also known as Wbp7) was required for the expression of
      Pigp, an essential component of the GPI-GlcNAc transferase, the enzyme catalyzing
      the first step of glycosylphosphatidylinositol (GPI) anchor synthesis. Impaired
      Pigp expression in Wbp7(-/-) macrophages abolished GPI anchor-dependent loading
      of proteins on the cell membrane. Consistently, loss of GPI-anchored CD14, the
      coreceptor for lipopolysaccharide (LPS) and other bacterial molecules, markedly
      attenuated LPS-triggered intracellular signals and gene expression changes. These
      data link a histone-modifying enzyme to a biosynthetic pathway and indicate a
      specialized biological role for Wbp7 in macrophage function and antimicrobial
      response.

PMID- 22483805
TI  - Formation of septanoses from hexopyranosides via 5,6-exo-glycals.
AB  - Methyl D-hexo-5-ulosides are obtained in high yield by dihydroxylation of 5,6-exo
      glucal compounds. The bicyclic structure (1,6-anhydropyrano-5-ulose) of the
      products is adopted in solution and in solid state in a (4)C(1) conformation.
      This methodology has been used to prepare 1,6-anhydro-L-idopyrano-5-uloses.
      Further manipulation of the 1,6-anhydro bridge allowed the preparation of the yet
      unknown septano-5-uloses in moderate to high yields.

PMID- 22483806
TI  - Prophylaxis against hepatitis B virus recurrence after liver transplantation for
      hepatitis B virus-related end-stage liver diseases with severe hypersplenism and
      splenomegaly: role of splenectomy.
AB  - BACKGROUND: The role of splenectomy on prophylaxis against hepatitis B virus
      (HBV) recurrence after liver transplantation (LT) for HBV-related end-stage liver
      diseases with severe hypersplenism and splenomegaly remains unclear today.
      METHODS: A total of 510 consecutive patients with HBV-related end-stage liver
      diseases who underwent LT in Liver Transplantation Center, West China Hospital,
      Sichuan University (Chengdu, China) between June 1999 and October 2009 were
      studied retrospectively in this study. Patients were divided into three groups in
      this study: splenectomized group (group A, n=137), including preoperatively
      splenectomized subgroup (group A1, n=48) and intraoperatively splenectomized
      subgroup (group A2, n=89); nonsplenectomized group with severe hypersplenism
      (group B, n=95); and nonsplenectomized group without severe hypersplenism (group
      C, n=278). The incidence of posttransplant rejection, posttransplant infection,
      posttransplant hepatic cell carcinoma recurrence rate, and HBV recurrence rate
      were recorded. The end of the follow-up period was October 2010. RESULTS: In this
      study, six patients with HBV recurrence were found in group A, 15 cases in group
      B, and 13 cases in group C during the follow-up period. (1) The incidence of
      posttransplant rejection in patients of group A was significantly lower than that
      in group B (P=0.0023) and also the HBV recurrence rates in group A markedly
      decreased (P=0.004). (2) The incidence of posttransplant rejection in group A was
      significantly lower than that in group C (P=0.0433); however, the incidence of
      posttransplant infection in group A largely increased compared with that in group
      C (P=0.0233). The HBV recurrence rates between group A and group C had no
      significant difference (P=0.804). (3) The HBV recurrence rates in group B were
      significantly higher than that in group C (P=0.001). CONCLUSIONS: The results of
      this study showed that splenectomy could significantly reduce the incidence of
      posttransplant rejection and HBV recurrence rate for the patients undergoing LT
      for HBV-related end-stage liver diseases with severe hypersplenism and
      splenomegaly.

PMID- 22483807
TI  - Technetium-99m sestamibi imaging: are the results dependent on the reviewer?
AB  - BACKGROUND: Minimally invasive parathyroidectomy (MIP) is dependent upon accurate
      preoperative parathyroid localization. We hypothesized that surgeon recognition
      of subtle differences in radiotracer accumulation would increase the sensitivity
      of technetium-99m sestamibi imaging and result in more frequent use of MIP.
      METHODS: Technetium-99m sestamibi scans completed at our institution for patients
      who underwent resection of a solitary parathyroid adenoma were reviewed by a
      surgeon and a radiologist who were blinded to patient identifying information,
      prior scan interpretation, and results of the operation. For each scan, the
      reviewer determined whether there was abnormal radiotracer accumulation and
      documented its location. Results were correlated with outcome of operation and
      final pathology. Blinded interpretations of the surgeon and radiologist were
      compared to each other and to the original radiologic interpretation. RESULTS:
      From 1994 to 2009, 274 patients with primary hyperparathyroidism (HPT) had
      sestamibi imaging prior to parathyroidectomy; 149 patients with a single adenoma
      underwent curative parathyroidectomy and had scans available for review.
      Seventeen radiologists who reviewed an average of 11 +/- 14 scans (range = 1-61)
      completed the original interpretations of the sestamibi imaging. Sensitivity of
      sestamibi imaging was 86% for the blinded surgeon compared to 75% for the blinded
      radiologist and 69% for the original radiologists (P < 0.05). There was no
      difference in the false positive rates (blinded surgeon = 5%, blinded radiologist
      = 5%, original radiologists = 5%, P > 0.05). CONCLUSION: Radiologists were less
      likely to call a scan positive. Surgeon recognition of subtle anatomic asymmetry
      increases the sensitivity of sestamibi imaging and successful completion of MIP.

PMID- 22483808
TI  - Comments on the association of increased morality with patients requiring pre
      hospital intubation after traumatic brain injury.

PMID- 22483809
TI  - Mitral annular velocity in patients with postoperative atrial fibrillation.
AB  - BACKGROUND: Subclinical atrial stunning (AS) (left atrial dysfunction) may
      increase vulnerability to oxidative and inflammatory stressors, thus increasing
      the likelihood of postoperative supraventricular arrhythmias, especially atrial
      fibrillation (AF). Evaluation of mitral annular velocities by tissue Doppler
      imaging (TDI) may be useful in seeking subclinical AS. This prospective study
      aimed to evaluate the relationship between atrial fibrillation after bypass
      surgery and presurgical determination of subclinical AS by assessing mitral
      annular velocities by TDI. METHODS: We enrolled patients who underwent coronary
      artery bypass graft (CABG) surgery into this prospective study. Inclusion
      criteria were sinus rhythm and a negative history of atrial tachycardia during
      the previous 3 mo. An experienced cardiologist performed transthoracic
      echocardiography in all patients. We recorded standard two-dimensional, mitral
      inflow conventional Doppler interrogation and TDI pulsed wave data from the
      lateral and septal annulus. All patients underwent CABG surgery at our
      Cardiovascular Surgery Unit. Patients were divided into two groups based on their
      postoperative AF status: group 1 patients had postoperative AF and group 2
      patients did not. RESULTS: This study included 44 patients. Age and the presence
      of chronic obstructive pulmonary disease were the only two significantly
      different parameters among clinical characteristics between groups.
      Echocardiographic findings that were statistically significantly different
      between groups were as follows: lateral A diastolic mitral annular velocity,
      group 1: 0.11 +/- 0.19 ms(-1)versus group 2: 0.08 +/- 0.19 ms(-1) (P = 0.001);
      lateral E diastolic mitral annular velocity, group 1: 0.69 +/- 0.24 ms(-1)versus
      group 2: 0.62 +/- 0.31 ms(-1) (P = 0.016); Septal E diastolic mitral annular
      velocity, group 1: 0.05 +/- 0.01 ms(-1)versus group 2: 0.04 +/- 0.01 ms(-1) (P =
      0.033); septal A diastolic mitral annular velocity, group 1: 0.08 +/- 0.02 ms(
      1)versus group 2: 0.05 +/- 0.02 ms(-1) (P = 0.005). CONCLUSIONS: There is no
      relationship between AF after CABG surgery and preexisting subclinical AS
      determined with mitral annular velocities by TDI. Preoperative appropriate
      prophylactic treatment should be administered to all patients.

PMID- 22483810
TI  - Collateral sensitivity as a strategy against cancer multidrug resistance.
AB  - While chemotherapy remains the most effective treatment for disseminated tumors,
      acquired or intrinsic drug resistance accounts for approximately 90% of treatment
      failure. Multidrug resistance (MDR), the simultaneous resistance to drugs that
      differ both structurally and mechanistically, often results from drug efflux
      pumps in the cell membrane that reduce intracellular drug levels to less than
      therapeutic concentrations. Expression of the MDR transporter P-glycoprotein (P
      gp, MDR1, ABCB1) has been shown to correlate with overall poor chemotherapy
      response and prognosis. This review will focus on collateral sensitivity (CS),
      the ability of compounds to kill MDR cells selectively over the parental cells
      from which they were derived. Insights into CS may offer an alternative strategy
      for the clinical resolution of MDR, as highly selective and potent CS agents may
      lead to drugs that are effective at MDR cell killing and tumor resensitization.
      Four main mechanistic hypotheses for CS will be reviewed, followed by a
      discussion on quantitative and experimental evaluation of CS.

PMID- 22483811
TI  - Mortality and causes of death among users of methadone maintenance treatment in
      Israel, 1999-2008.
AB  - OBJECTIVES: To determine all-cause and specific-causes mortality, in the years
      1999-2008, among opioid-dependent users treated at methadone maintenance
      treatment (MMT) clinics in Israel and to compare the obtained results with data
      from relevant studies worldwide. METHOD: The records of patients treated at MMT
      units were linked to the nationwide database of causes of death. Information
      about the Israeli general population from the Central Bureau of Statistics was
      used for comparison to match sex and age to the cohort under study. Crude
      mortality rates (CMRs) per 100 persons per year (PY) and standardized mortality
      ratios (SMRs) with 95% confidence intervals (CIs) were calculated. RESULTS: The
      overall CMR for MMT users was 1.49/100 PY (CI 1.40-1.59) and was not associated
      with gender, age at entering MMT, ethnicity, and immigrant status. The leading
      causes of mortality were sudden/undefined death (0.31/100 PY, CI 0.26-0.35),
      overdose (0.22/100 PY, CI 0.17-0.27), and cancer (0.15/100 PY, CI 0.12-0.18). The
      MMT users were 12.2 times more likely to die from all causes than people from the
      general population. Overall, our estimates were comparable with the figures
      pooled from relevant studies. CONCLUSIONS: The results suggest that the excess
      mortality of MMT users is associated with an increased morbidity, which alone or
      in combination with service-related risks, lead to worse outcomes.

PMID- 22483812
TI  - Adolescent exposure to nicotine results in reinforcement enhancement but does not
      affect adult responding in rats.
AB  - BACKGROUND: Adolescence is a period of development associated with a peak in an
      organism's responsiveness to reward. Epidemiological data indicate that the
      initiation of smoking is high during adolescence and that earlier age of onset is
      associated with increased incidence of dependence as adults. In rats, nicotine is
      known to have primary reinforcing and reinforcement enhancing effects. Although
      the primary reinforcing effects of nicotine have been demonstrated in adolescent
      rats (self-administration), less is known about its reinforcement enhancing
      effects during this period. Moreover, the impact of adolescent nicotine exposure
      on its reinforcement enhancing effects during adulthood has not yet been
      examined. The objectives of this study were to assess whether (1) nicotine
      enhances operant responding for an unconditioned visual reinforcer (VS) in
      adolescent rats, and (2) exposure to nicotine during adolescence affects
      responsiveness to the VS in adulthood. METHODS: Rats were exposed to nicotine
      (0.32 mg/kg, subcutaneous injection) or saline during adolescence (postnatal day
      29-42) and adulthood. Nose-poking for the VS was assessed under fixed and
      progressive ratio schedules. RESULTS: Nicotine increased responding for the VS
      during adolescence. Adolescent nicotine exposure failed to significantly affect
      adult responsiveness for the VS, regardless of adult nicotine exposure, but early
      exposure to the VS affected responsiveness to the VS in adulthood. CONCLUSIONS:
      Nicotine exhibits reinforcement enhancing effects in adolescent rats. Long-term
      effects of adolescent nicotine on reinforcement enhancement are minimal, but the
      impact of early exposure to the VS and/or the primary reinforcing effects of
      nicotine requires further investigation.

PMID- 22483813
TI  - Voluntary attention reliably influences visual processing at the level of the C1
      component: a commentary on Fu, Fedota, Greenwood, and Parasuram (2010).

PMID- 22483814
TI  - Epidemiology and natural history of vestibular schwannomas.
AB  - This article describes various epidemiologic trends for vestibular schwannomas
      over the last 35 years, including a brief note on terminology. Additionally, it
      provides information on the natural history of tumor growth and hearing level
      following the diagnosis of a vestibular schwannoma. A treatment strategy based on
      the natural history of tumor growth and hearing also is discussed.

PMID- 22483815
TI  - Clinical and diagnostic evaluation of acoustic neuromas.
AB  - In the past century, significant advances have been made in understanding the
      clinical features of acoustic neuromas. Furthermore, rapid technological advances
      have led to the development of sensitive, rapid, and relatively noninvasive
      diagnostic modalities, which has allowed for earlier discovery of acoustic
      neuromas and has reduced the average tumor size at time of diagnosis. The
      ultimate result has been improved clinical outcomes after surgery and
      radiotherapy.

PMID- 22483816
TI  - Preoperative, intraoperative, and postoperative auditory evaluation of patients
      with acoustic neuroma.
AB  - This article is a concise clinical review of preoperative, intraoperative, and
      postoperative auditory evaluation of patients with acoustic neuroma. The author
      describes behavioral audiometry, auditory brainstem response, and otoacoustic
      emissions for preoperative evaluation; auditory brainstem and direct eighth-nerve
      intraoperative monitoring for intraoperative evaluation; and touches on
      postoperative auditory assessment.

PMID- 22483817
TI  - Acoustic neuroma neurophysiologic correlates: facial and recurrent laryngeal
      nerves before, during, and after surgery.
AB  - This article focuses on the facial nerve with additional comments on the
      recurrent laryngeal nerve as a proxy for the lower cranial nerves. Methods,
      advantages and disadvantages, and techniques are listed. The article addresses
      the anatomy of the facial nerve, discusses neurophysiologic testing, the role of
      electroneurography in preoperative, intraoperative, and postoperative testing,
      and presents 7 steps to set up for and perform facial nerve monitoring. Details
      are provided on interpretation of testing, and the pitfalls of interpretation are
      discussed. Studies are reviewed presenting outcomes of testing.

PMID- 22483818
TI  - Acoustic neuroma neurophysiologic correlates: vestibular-preoperative,
      intraoperative, and postoperative.
AB  - By the nature of their origin, acoustic neuromas always result in some degree of
      vestibular dysfunction. The implications of this are typically more notable
      postoperatively, rather than preoperatively or intraoperatively. However,
      preoperative vestibular assessment can have implications on operative approach
      and postoperative rehabilitation. This paper details the preoperative vestibular
      findings that correlate with differing stages of acoustic neuroma growth. It also
      describes the findings that help localize the tumor origin to either the inferior
      or superior divisions of the vestibular nerve. Finally, and probably most
      importantly, we discuss the causes of persistent postoperative vestibular
      symptoms.

PMID- 22483819
TI  - Neurofibromatosis 2.
AB  - A comprehensive discussion of neurofibromatosis 2 (NF2) is presented, including
      clinical characteristics, symptoms, diagnosis, tumor types, prevalence and
      incidence, genetic testing, imaging, treatment options, and follow-up management
      of NF2.

PMID- 22483820
TI  - The art of management decision making: from intuition to evidence-based medicine.
AB  - This article summarizes available evidence on various management options for
      vestibular schwannoma as they relate to the decision-making strategies used in
      selection. After a brief consideration of individual options, the literature
      directly comparing two or more management options is examined, noting the level
      of evidence supporting their claims. A discussion of the strategies developed to
      guide decision making follows. The article closes with a summary of the evidence
      based findings and suggestions for further research. The focus is on management
      of sporadic, unilateral vestibular schwannomas, because patients with
      neurofibromatosis type 2 pose different management problems best discussed
      separately.

PMID- 22483821
TI  - Radiation therapy and radiosurgery for vestibular schwannomas: indications,
      techniques, and results.
AB  - This article describes in detail the uses of and distinctions between
      stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for
      vestibular schwannoma (VS). The authors discuss devices and techniques used in
      SRS and SRT and, additionally, present readers the approach used by surgeons at
      Mayo Clinic. They discuss indications and results for both approaches in patients
      with vestibular schwannoma. Treatment of small and large tumors is discussed,
      along with cystic tumors and NF2-associated VS. Repeating SRS for vestibular
      schwannoma is also mentioned.

PMID- 22483822
TI  - Management of radiation/radiosurgical complications and failures.
AB  - To describe the incidence and the course of complications after the radiosurgical
      treatment of vestibular schwannomas, the authors reviewed their own experience
      and reviewed the literature. Failure is described in less than 3% of cases, and
      this had to be distinguished from transient enlargement of tumor volume. In case
      of failure, microsurgical resection or another radiosurgical procedure should be
      discussed. The risk of radio-induced tumorigenesis is not clearly established
      with single-dose radiosurgical technique. Incidence and management of potential
      complications should be explained at the time of decision making in the
      management of vestibular schwannomas.

PMID- 22483823
TI  - Retrosigmoid approach: indications, techniques, and results.
AB  - This review describes the indications and techniques for the retrosigmoid
      approach for vestibular schwannoma, as performed by the skull base surgery group
      at the University of Miami. The authors present background of the retrosigmoid
      approach, surgical steps, and essential "technical pearls" to address
      complication avoidance, resulting from their expertise with this surgery.

PMID- 22483824
TI  - Translabyrinthine approach: indications, techniques, and results.
AB  - This article presents a comprehensive review of the translabyrinthine surgical
      approach for vestibular schwannoma. Additionally, it addresses the traditional
      labyrinthectomy and identifies a time-efficient version. Indications and outcomes
      of the approach are presented, along with detailed procedural technique from
      opening incision through closure. Complications and management of complications
      are discussed in detail, as well as postoperative patient care.

PMID- 22483825
TI  - Middle fossa approach: indications, technique, and results.
AB  - This article discusses the indications, surgical technique, results, and
      complications of middle fossa craniotomy (MFC) for vestibular schwannoma surgery,
      focusing on issues such as serviceable hearing, tumor characteristics, and
      patient-specific factors that help determine options for therapy. MFC is suitable
      for intracanalicular vestibular schwannomas that extend less than 1 cm into the
      cerebellopontine angle in patients with good hearing. With the expanding use of
      modern imaging, many small tumors are being identified in patients with no or
      minimal symptoms. Patients with these tumors have three therapy options: (1)
      stereotactic radiotherapy, (2) microsurgery, and (3) observation (ie, wait-and
      scan approach).

PMID- 22483826
TI  - The endoscopic approach to vestibular schwannomas and posterolateral skull base
      pathology.
AB  - This article provides an overview of the technical considerations of endoscopy of
      the posterolateral skull base and cerebellopontine angle (CPA). Specific areas of
      focus are on the instrumentation requirements for neuroendoscopy of the CPA; the
      learning curve associated with this technique; and a complete description of the
      surgical techniques necessary to perform the procedure, along with outcomes and
      results. The article provides a general overview of the endoscopic approach to
      the CPA. For a variety of pathologies, the emphasis is on performing this
      technique for acoustic tumors and hearing preservation. Insights as to how the
      author's practice evolved in its use of neuroendoscopic procedures are provided.

PMID- 22483827
TI  - Management of surgical complications and failures in acoustic neuroma surgery.
AB  - Acoustic neuromas (ANs) are the most common tumors of the cerebellopontine angle.
      Although numerous advances have occurred in the operative management of AN and
      perioperative care leading to a significant decrease in associated morbidity and
      mortality, there are several characteristic complications that accompany
      microsurgical resection of AN. Understanding the types and rates of complications
      in association with the various approaches is essential in patient counseling,
      establishing patient expectations, and ensuring the best patient outcome. In this
      article, the justification for incomplete surgical resection is discussed. Also,
      the most common complications of AN microsurgery and the associated management
      are reviewed.

PMID- 22483828
TI  - Chemotherapy: present and future.
AB  - Vestibular schwannomas (VS) are among the most common benign tumors of the
      central nervous system. Bilateral VS are the hallmark of neurofibromatosis type
      II, commonly leading to complete deafness and cranial nerve deficits as a result
      of tumor progression or treatment with surgery or radiation. Effective medical
      therapies are needed to address tumor progression and treatment-related
      morbidity. This article reviews the standard therapies for VS, summarizes the
      molecular biology of these tumors, and describes potential targets for
      chemotherapeutic agents. The article also defines and recommends the use of
      specific clinical end points in future drug trials, describes previous and
      current experience with anti-VEGF and anti-EGFR agents, and delineates areas of
      future research.

PMID- 22483829
TI  - Habilitation of auditory and vestibular dysfunction.
AB  - Although unilateral hearing loss is often the initial sign of vestibular
      schwannoma (VS), the pathogenesis of the associated structures within the
      cerebellopontine angle can result in vestibular, facial, or vascular symptoms.
      Removal of a VS causes deficits in hearing, balance, and gaze stability. The
      resulting hearing loss eliminates the benefits of binaural listening that provide
      localization, loudness summation, and listening-in-noise ability. Reduced balance
      and gaze stability increase fall risk. This review discusses modern treatment
      options for auditory and vestibular rehabilitation including contralateral
      routing of signals (CROS), bilateral CROS, bone-anchored implants, tinnitus
      management, gaze and gait stability exercises.

PMID- 22483830
TI  - Habilitation of facial nerve dysfunction after resection of a vestibular
      schwannoma.
AB  - Facial nerve dysfunction after resection of a vestibular schwannoma is one of the
      most common indications for facial nerve habilitation. This article presents an
      overview of common and emerging management options for facial habilitation
      following resection of a vestibular schwannoma. Immediate and delayed nerve
      repair options, as well as adjunctive surgical, medical, and physical therapies
      for facial nerve dysfunction, are discussed. Two algorithms are provided as
      guides for the assessment and treatment of facial nerve paralysis after resection
      of vestibular schwannoma.

PMID- 22483831
TI  - Importance of local support groups for acoustic neuroma and neurofibromatosis
      patients.
AB  - Local support groups are an important part of the support network for acoustic
      neuroma and neurofibromatosis patients. For many people, the local support group
      is the only place where they can make personal contact with other patients who
      have gone through a similar experience. This article specifically looks at the
      Acoustic Neuroma Association and Neurofibromatosis, Incorporated and describes
      how these organizations help individuals.

PMID- 22483832
TI  - Vestibular schwannoma (acoustic neuroma).

PMID- 22483833
TI  - Vestibular schwannoma: evidence-based treatment.

PMID- 22483834
TI  - Long-term field test of an electrochemical method for sulfide removal from
      sewage.
AB  - Corrosion caused by hydrogen sulfide leads to significant costs for the
      rehabilitation or replacement of corroded sewer pipes. Conventional methods to
      prevent sewer corrosion normally involve the dosing of significant amounts of
      chemicals with the associated transport and storage costs as well as considerable
      maintenance and control requirement. Recently, a novel chemical free method for
      sulfide abatement based on electrochemical sulfide oxidation was shown to be
      highly effective for the removal of sulfide from synthetic and real sewage. Here,
      we report on the electrochemical removal of sulfide using Ta/Ir and Pt/Ir coated
      titanium electrodes under simulated sewer conditions during field trials. The
      results showed that sulfide can successfully be removed to levels below the
      normal target value at the end of a simulated rising main (i.e. <1mg/L). A
      coulombic efficiency for dissolved oxygen generation of ~ 60% was obtained and
      was independent of the current density. Scaling of the electrode and the membrane
      was observed in the cathode compartment and as a result the cell potentials
      increased over time. The cathode potentials returned to their original potential
      after switching the polarity every two days, but a more frequent switching would
      be needed to reduce the energy requirements of the system. Accelerated lifetime
      experiments indicated that a lifetime of 6.0 +/- 1.9 years can be expected under
      polarity switching conditions at a pH of 14 and significantly longer at lower pH
      values. As operating the system without switching simplifies construction as well
      as operation, the choice whether to switch or not will in practice depend on
      operational cost (higher/lower energy) versus capital cost (reactor and
      peripherals). Irrespective of the approach, our study demonstrates that
      electrochemical sulfide control in sewer systems may be an attractive new option.

PMID- 22483835
TI  - Effects of hydraulic and solids retention times on productivity and settleability
      of microbial (microalgal-bacterial) biomass grown on primary treated wastewater
      as a biofuel feedstock.
AB  - High biomass productivity and efficient harvesting are currently recognized
      challenges in microbial biofuel applications. To produce naturally settleable
      biomass, combined growth of native microalgae and bacteria was facilitated in
      laboratory sequencing batch reactors (SBRs) using primary treated wastewater from
      the Christchurch Wastewater Treatment Plant (CWTP) in New Zealand. SBRs were
      operated under a simulated, local, summer climate (i.e., 925 MUmol/m(2)/s of
      photosynthetically active radiation for 14.7 h per day at 21  degrees C mean
      water temperature) using 1.4- to 8-day hydraulic retention times (HRTs) to
      optimize growth. Solids retention times (SRTs) were varied from 4 to 40 days by
      discharging different ratios of supernatant and completely mixed culture. Biomass
      productivity up to 31 g/m(2)/day of solids was obtained, and it generally
      increased as retention times decreased. Biomass settleability was typically 70
      95%, and the microbes aggregated into compact flocs as cultures aged up to four
      months. Due to a low lipid content of 10.5%, anaerobic digestion appeared to be
      the most appropriate biofuel conversion process with potential to generate 19,200
      m(3)/ha/yr of methane based on settleable mixture productivity.

PMID- 22483836
TI  - Review of photochemical reaction constants of organic micropollutants required
      for UV advanced oxidation processes in water.
AB  - Emerging organic contaminants (pharmaceutical compounds, personal care products,
      pesticides, hormones, surfactants, fire retardants, fuel additives etc.) are
      increasingly found in water sources and therefore need to be controlled by water
      treatment technology. UV advanced oxidation technologies are often used as an
      effective barrier against organic contaminants. The combined operation of direct
      photolysis and reaction with hydroxyl radicals ensures good results for a wide
      range of contaminants. In this review, an overview is provided of the
      photochemical reaction parameters (quantum yield, molar absorption, OH radical
      reaction rate constant) of more than 100 organic micropollutants. These
      parameters allow for a prediction of organic contaminant removal by UV advanced
      oxidation systems. An example of contaminant degradation is elaborated for a
      simplified UV/H(2)O(2) system.

PMID- 22483837
TI  - Removing 17beta-estradiol from drinking water in a biologically active carbon
      (BAC) reactor modified from a granular activated carbon (GAC) reactor.
AB  - Estrogenic compounds in drinking water sources pose potential threats to human
      health. Treatment technologies are needed to effectively remove these compounds
      for the production of safe drinking water. In this study, GAC adsorption was
      first tested for its ability to remove a model estrogenic compound, 17beta
      estradiol (E2). Although GAC showed a relatively high adsorption capacity for E2
      in isotherm experiments, it appeared to have a long mass transfer zone in a GAC
      column reactor, causing an early leakage of E2 in the effluent. With an influent
      E2 concentration of 20 MUg/L, the GAC reactor was able to bring down effluent E2
      to ~ 200 ng/L. To further enhance E2 removal, the GAC reactor was converted to a
      biologically active carbon (BAC) reactor by promoting biofilm growth in the
      reactor. Under optimal operating conditions, the BAC reactor had an effluent E2
      concentration of ~ 50 ng/L. With the empty bed contact times tested, the reactor
      exhibited more robust E2 removal performance under the BAC operation than under
      the GAC operation. It is noted that estrone (E1), an E2 biodegradation
      intermediate, was frequently detected in reactor effluent during the BAC
      operation. Results from this study suggested that BAC could be an effective
      drinking water treatment process for E2 removal and in the meantime E1
      accumulation needs to be addressed.

PMID- 22483838
TI  - Phyto-synthesis of silver nanoscale particles using Morinda citrifolia L. and its
      inhibitory activity against human pathogens.
AB  - Leaf extract of Morinda citrifolia L. was assessed for the synthesis of silver
      nanoscale particles under different temperature and reaction time. Synthesized
      nanoscale (MCAgNPs) particles were confirmed by analysing the excitation of
      surface plasmon resonance (SPR) using UV-visible spectrophotometer at 420 nm.
      Further SEM, HRTEM analysis confirmed the range of particle size between 10 and
      60 nm and SEAD pattern authorizes the face centered cubic (fcc) crystalline
      nature of the MCAgNPs. Fourier transform infrared spectrum (FTIR) of synthesized
      MCAgNPs confirms the presence of high amount of phenolic compounds in the plant
      extract which may possibly influence the reduction process and stabilization of
      nanoparticles. Further, inhibitory activity of MCAgNPs and plant extract were
      tested against human pathogens like Eschericia coli, Pseudomonas aeroginosa,
      Klebsiella pneumoniae, Enterobacter aerogenes, Bacillus cereus and Enterococci
      sp. The results indicated that the MCAgNPs showed moderate inhibitory actions
      against human pathogens than crude plant extract, demonstrating its antimicrobial
      value against pathogenic diseases.

PMID- 22483839
TI  - Age and living in an urban environment are major determinants of diabetes among
      South Kivu Congolese adults.
AB  - OBJECTIVES: This study aimed to determine the risk factors for diabetes mellitus
      (DM) in the eastern part of the Democratic Republic of Congo. METHODOLOGY:
      Multilevel sampling identified 200 households (444 adults aged >= 20 years) from
      20 neighbourhoods in the city of Bukavu, and 90 households (255 adults aged >= 20
      years) from 10 villages in the Kaziba (South Kivu) chiefdom (the South Kivu
      VITARAA study). DM was defined as a personal history of the disorder or a casual
      glycaemia greater or equal to 200 mg/dL. Standardization according to age and
      sample readjustment based on the urban-rural distribution of the population was
      applied accordance with the typical Congolese population. The probability of DM
      was assessed by multiple logistic regressions. RESULTS: Total prevalence of DM
      was 3.5%. DM was significantly more prevalent in urban areas (age-standardized
      prevalence: 4.0%) than in rural areas (1.7%). City-dwelling DM patients were
      characterized by higher rates of indices of abdominal obesity (P < 0.05) whereas,
      in rural areas, no patients were obese. In the study group as a whole, only 25.0%
      of diabetic patients were obese. On multivariate analyses, only age [adjusted OR
      (95% CI): 4.79 (1.60-14.25); P = 0.004] was independently associated with the
      prevalence of DM, while the effect of obesity was not significant [2.64 (0.99
      7.02); P = 0.051]. CONCLUSION: Age and living in an urban environment appeared to
      be major determinants of DM in South Kivu. Also, obesity prevalence was
      relatively low in these diabetic patients, confirming the peculiar, relatively
      lean, phenotype of type 2 DM in indigenous sub-Saharan Africans.

PMID- 22483840
TI  - Solution NMR analysis of the binding mechanism of DIVS6 model peptides of voltage
      gated sodium channels and the lipid soluble alkaloid veratridine.
AB  - Voltage-gated sodium channels (VGSCs) are responsible for generating action
      potentials in nervous systems. Veratridine (VTD), a lipid soluble alkaloid
      isolated from sabadilla lily seed, is believed to bind to segment 6 of VGSCs and
      act as a partial agonist. However, high resolution structural interaction
      mechanism between VGSCs and VTD is difficult to elucidate because of the large
      size and membrane localization of VGSCs. Here, the authors designed model
      peptides corresponding to domain IV segment 6 (DIVS6) of rat skeletal muscle
      Na(v)1.4 and analyzed the complex of the model peptides and VTD by solution NMR
      analysis to obtain structural information of the interaction. The model peptides
      successfully formed an alpha-helices, which is the suspected native conformation
      of DIVS6, in aqueous 2,2,2-trifluoroethanol, a membrane-mimicking solvent. The
      VTD binding residues of the model peptide were identified using the NMR titration
      experiments with VTD, including a newly discovered VTD binding residue Leu14 (MU1
      L1580 in Na(v)1.4), which has not been reported by point mutation studies.
      Mapping of VTD binding residues on the model peptide revealed the hydrophobic
      interaction surface. NMR titration experiments with a non-toxic analog of VTD,
      veracevine, also indicated that the steroidal backbone of VTD interacts with the
      hydrophobic interaction surface of DIVS6 and that the 3-acyl group of VTD
      possibly causes neurotoxicity by interacting with domain I segment 6 and/or
      domain IV segment 4.

PMID- 22483841
TI  - Chemoinformatics: a view of the field and current trends in method development.
AB  - The chemoinformatics field continues to evolve at the interface between computer
      science and chemistry. Chemical information and computational approaches in
      pharmaceutical research are major focal points of chemoinformatics. However, the
      boundaries of this discipline are rather fluid and the chemoinformatics spectrum
      is difficult to delineate. The field is in flux, which also provides
      opportunities for further developments. As a lead-in to the Chemoinformatics
      Symposium-in-Print, we present a brief view of this discipline (with a little
      anecdotal touch), highlight current trends in method development, and discuss a
      number of representative examples.

PMID- 22483842
TI  - Mixed poly-brominated/chlorinated biphenyls (PXBs): widespread food and
      environmental contaminants.
AB  - Mixed poly-brominated/chlorinated biphenyls (PXBs) are a new class of emerging
      contaminants. Their environmental occurrence is confirmed by the reported
      occurrence in foods and human tissues, and the patterns of occurrence suggest
      that different sources may be contributing to food occurrence in different parts
      of the world. Important sources of PXBs are thought to include emissions from the
      combustion of bromine and chlorine containing waste and consumer products and
      inadvertent contamination in industrial chemicals. Of specific interest are the
      dioxin-like-PXBs. These are the 62 non-ortho-substituted PXBs with eight
      congeners of 3,3',4,4'-substitution type (#77A-H), ten of 3,4,4',5-type (#81A-J),
      twenty four of 3,4,5,3',4'-type (#126A-Z) and twenty of 3,4,5,3',4',5'-type
      (#169A-V) and many mono-ortho substituted compounds. The toxicological
      clarification on these contaminants continues, with reports confirming dioxin
      like effects at low concentrations, suggesting a greater toxicological
      significance than PCBs.

PMID- 22483843
TI  - International electives at the university of Minnesota global pediatric residency
      program: opportunities for education in all Accreditation Council for Graduate
      Medical Education competencies.
AB  - PURPOSE: Globally competent pediatricians are in demand because of the increasing
      numbers of children from immigrant families living in the United States and the
      shortages of health care workers in low-income countries where the majority of
      the worlds' children live. This study sought to better understand the educational
      outcomes of international electives taken by pediatric residents training in
      global health. METHODS: Thirty-two pediatric residents who participated in an
      international elective as part of a global health curriculum completed reflective
      essays which were analyzed for themes from 2006 to 2010. During the first-order
      analysis, the emergent themes mapped to the Accreditation Council for Graduate
      Medical Education (ACGME) competencies. In response, a second-order analysis re
      examined the essays with an additional researcher to support categorization
      consistent with the ACGME competencies. RESULTS: More than 90% of essays
      described experiences related to medical knowledge, patient care and systems
      based practice. More than 50% included reflections on practice-based learning and
      improvement, professionalism, and interpersonal and communication skills.
      Residents also described the impact on their personal and professional
      development. CONCLUSION: International electives can provide educational
      opportunities for residents to develop competency in each of the 6 ACGME domains
      and to reevaluate their life purpose and career goals. In addition to
      opportunities to increase their medical knowledge, patient care and communication
      skills, residents find international electives rich learning environments for
      systems-based practice, practice-based learning/improvement, and professionalism,
      domains that can be challenging to teach. These findings support the importance
      of international electives in global health in meeting core requirements in
      residency training.

PMID- 22483844
TI  - Chest radiological findings of influenza A H1N1 pneumonia.
AB  - OBJECTIVE: The objective of this study was to review chest radiographs (CXR) and
      chest computer tomography (CT) findings in patients with influenza A H1N1 virus
      pneumonia. MATERIALS AND METHODS: Of ninety-eight patients with influenza A H1N1
      infections seen in the General Hospitals of Villa Scassi, Genoa, and Sestri
      Levante from September 2009 to December 2009, twenty-eight developed pneumonia.
      The initial CXR were evaluated for radiological patterns: (ground-glass,
      consolidation, nodules, reticulation), distribution, and extent of the disease.
      Chest CT scans were reviewed for the same findings. A new radiographic score (CXR
      score) was used to evaluate the severity of the illness. RESULTS: The predominant
      radiological findings on chest CT in the patients at presentation were unilateral
      or bilateral multifocal ground glass opacities (84.5% of the patients).
      Consolidation areas had a peribronchovascular and subpleural predominance and
      were found mainly in the middle and upper zones of the lung. Reticular opacities
      were found in about 20% of the cases. The most outstanding CXR and chest CT
      features of the disease were basal and axial alveolar consolidation and ground
      glass opacities. The severity of disease as determinate by need for mechanical
      ventilation was greater in patients with a greater number of lobes involved and a
      higher CXR score. CONCLUSION: Bilateral ground-glass opacities and areas of
      consolidation were the predominant radiological findings of influenza A (H1N1)
      virus pneumonia. Multifocal bilateral opacities and CXR score are strictly
      correlated with the severity of the illness.

PMID- 22483845
TI  - Comparison of 3'-deoxy-3'-[18F]fluorothymidine PET and O-(2-[18F]fluoroethyl)-L
      tyrosine PET in patients with newly diagnosed glioma.
AB  - PURPOSE: The purpose of this prospective study was to clarify the value of FLT
      PET and FET PET for the noninvasive grading and prognosis of newly diagnosed
      gliomas. MATERIALS AND METHODS: Twenty patients with newly diagnosed gliomas were
      investigated with FLT and FET PET before surgery. FLT and FET uptakes were
      assessed by the maximum standardized uptake (SUVmax) of tumor, and the ratio to
      uptake in the normal brain parenchyma (TNR). All tumors were graded by WHO
      system. RESULTS: FLT PET detected all 17 high-grade gliomas (HGG) and did not
      detect all 3 low-grade gliomas (LGG). FET PET detected all 20 HGG and LGG
      regardless of grading. The average FLT SUVmax in HGG and LGG was 1.51 +/- 0.72
      and 0.30 +/- 0.07, and the average FLT TNR in HGG and LGG was 5.52 +/- 3.09 and
      1.12 +/- 0.14, respectively. The differences of FLT SUVmax and TNR between HGG
      and LGG were statistically significant (p=0.0069, p=0.0070). The average FET
      SUVmax in HGG and LGG was 2.68 +/- 0.86 and 1.36 +/- 0.15, and the average FET
      TNR in HGG and LGG was 2.31 +/- 0.73 and 1.27 +/- 0.12, respectively. The
      differences of FET SUVmax and TNR between HGG and LGG were statistically
      significant (p=0.0129, p=0.0095). CONCLUSIONS: FET PET has higher sensitivity in
      detection of gliomas rather than FLT PET, but it seems that FLT PET is better
      than FET PET for noninvasive grading and predicting prognosis of newly diagnosed
      gliomas, considering high contrast of FLT and overlap of FET uptakes between HGG
      and LGG.

PMID- 22483846
TI  - Thrombotic microangiopathy and acute kidney injury in hump-nosed viper (Hypnale
      species) envenoming: a descriptive study in Sri Lanka.
AB  - Hump-nosed viper (Hypnale species) bites are common in Sri Lanka and a proportion
      of these bites lead to coagulation abnormalities and acute kidney injury (AKI).
      We observed thrombotic microangiopathy (TMA) among some of these patients, but
      its contribution to severity of AKI and other morbidities remains unknown. Thus,
      we report a case series of TMA following hump-nosed viper bite addressing the
      complications and renal out comes in Sri Lanka. This was a prospective
      observational study carried out at the nephrology unit, Kandy in Sri Lanka from
      October 2010 to October 2011 and included 11 patients with AKI following hump
      nosed viper bites. All eleven cases needed renal replacement therapy (RRT) with
      intermittent haemodialysis for a period of 1-5 weeks. Of them, 7 patients
      developed TMA with evidence of microangiopathic haemolytic anaemia (MAHA),
      thrombocytopenia and severe anaemia needing multiple blood transfusions. They
      needed longer duration of RRT (range 2-5 weeks); 2 patients developed chronic
      kidney disease and two died during acute stage. Autopsy study found thrombosis of
      micro-vessels. Thrombotic microangiopathy could be a causative pathology of AKI
      in hump-nosed viper bite carrying poor outcome.

PMID- 22483847
TI  - Batroxase, a new metalloproteinase from B. atrox snake venom with strong
      fibrinolytic activity.
AB  - The structures and functional activities of metalloproteinases from snake venoms
      have been widely studied because of the importance of these molecules in
      envenomation. Batroxase, which is a metalloproteinase isolated from Bothrops
      atrox (Para) snake venom, was obtained by gel filtration and anion exchange
      chromatography. The enzyme is a single protein chain composed of 202 amino acid
      residues with a molecular mass of 22.9 kDa, as determined by mass spectrometry
      analysis, showing an isoelectric point of 7.5. The primary sequence analysis
      indicates that the proteinase contains a zinc ligand motif (HELGHNLGISH) and a
      sequence C164 I165M166 motif that is associated with a "Met-turn" structure. The
      protein lacks N-glycosylation sites and contains seven half cystine residues, six
      of which are conserved as pairs to form disulfide bridges. The three-dimensional
      structure of Batroxase was modeled based on the crystal structure of BmooMPalpha
      I from Bothrops moojeni. The model revealed that the zinc binding site has a high
      structural similarity to the binding site of other metalloproteinases. Batroxase
      presented weak hemorrhagic activity, with a MHD of 10 MUg, and was able to
      hydrolyze extracellular matrix components, such as type IV collagen and
      fibronectin. The toxin cleaves both alpha and beta-chains of the fibrinogen
      molecule, and it can be inhibited by EDTA, EGTA and beta-mercaptoethanol.
      Batroxase was able to dissolve fibrin clots independently of plasminogen
      activation. These results demonstrate that Batroxase is a zinc-dependent
      hemorrhagic metalloproteinase with fibrin(ogen)olytic and thrombolytic activity.

PMID- 22483848
TI  - G-protein coupled receptor-associated sorting protein 1 (GASP-1), a ubiquitous
      tumor marker.
AB  - Using an innovative "2-D high performance liquid electrophoresis" (2-D HPLE)
      technology we identified that a specific fragment of G-protein coupled receptor
      associated sorting protein 1 (GASP-1) was present in the sera of breast cancer
      patients and was over-expressed in early and late stage breast tumors (Tuszynski,
      G.P. et al., 2011). In this study we further investigated the significance of
      GASP-1 as a tumor marker by investigating the expression GASP-1 in different
      kinds of tumors as well as in the sera of patients with various cancers. Over
      expression of GASP-1 was detected in brain, pancreatic, and breast cancers as
      compared to their respective normal tissues as assessed by immunohistochemical
      staining of tissue arrays using a "peptide specific" GASP-1 antibody. We found
      that across these cancers, GASP-1 was expressed approximately 10 fold more in the
      cancer as compared to normal tissue. The increase in GASP-1 expression was also
      seen in hyperplastic and inflammatory lesions of breast and pancreatic cancers as
      compared to normal tissue. GASP-1 was primarily expressed in the tumor epithelium
      of the epithelial-derived cancers and in the transformed glial cells of the brain
      tumors. Using a sensitive "competitive ELISA" for GASP-1, we found that sera from
      patients with brain, liver, breast and lung cancers expressed 4-7 fold more GASP
      1 peptide than sera from normal healthy individuals. These studies identify GASP
      1 as a potential new serum and tumor biomarker for several cancers and suggest
      that GASP-1 may be a novel target for development of cancer therapeutics.

PMID- 22483850
TI  - The virB-encoded type IV secretion system is critical for establishment of
      infection and persistence of Brucella ovis infection in mice.
AB  - Brucella spp. are gram-negative intracellular bacterial pathogens that cause
      chronic infections. Brucella virulence factors include a type IV secretion system
      (T4SS) and its lipopolysaccharide (LPS), which are essential for persistence.
      However, the role of the virB-encoded T4SS has not been investigated in naturally
      rough Brucella species such as Brucella ovis. In this study, male 6-week old
      BALBc mice were infected with B. ovis, Brucella abortus, and their respective
      DeltavirB2 mutant strains. During early infection, B. ovis and B. abortus wild
      type strains were similarly recovered from spleen. Interestingly, in contrast to
      DeltavirB2 B. abortus that was recovered at similar levels when compared to the
      wild type strain, the DeltavirB2 B. ovis was markedly attenuated as early as 24h
      post infection (hpi). The DeltavirB2 B. ovis was unable to survive and multiply
      in murine peritoneal macrophages and extracellularly within the peritoneal cavity
      at 12 and 24 hpi with lower splenic colonization than the parental strain at 6,
      12 and 24 hpi. In contrast, wild type B. abortus and DeltavirB2 B. abortus had a
      similar kinetics of infection in this model. As expected, the T4SS was essential
      for intracellular replication of smooth and rough strains in RAW macrophages at
      48 hpi. These results suggest that T4SS is important for survival of B. ovis in
      murine model, and that a T4SS deficient B. ovis strain is cleared at earlier
      stages of infection when compared to a similar B. abortus mutant.

PMID- 22483851
TI  - Dynamic regulation of growing domains for elongating and branching morphogenesis
      in plants.
AB  - With their continuous growth, understanding how plant shapes form is
      fundamentally linked to understanding how growth rates are controlled across
      different regions of the plant. Much of a plant's architecture is generated in
      shoots and roots, where fast growth in tips contrasts with slow growth in
      supporting stalks. Shapes can be determined by where the boundaries between fast-
      and slow-growing regions are positioned, determining whether tips elongate,
      branch, or cease to grow. Across plants, there is a diversity in the cell wall
      chemistry through which growth operates. However, prototypical morphologies, such
      as tip growth and branching, suggest there are common dynamic constraints in
      localizing chemical growth catalysts. We have used Turing-type reaction-diffusion
      mechanisms to model this spatial localization and the resulting growth
      trajectories, characterizing the chemistry-growth feedback necessary for
      maintaining tip growth and for inducing branching. The mechanism defining the
      boundaries between fast- and slow-growing regions not only affects tip shape, it
      must be able to form new boundaries when the pattern-forming dynamics break
      symmetry, for instance in the branching of a tip. In previous work, we used an
      arbitrary concentration threshold to switch between two dynamic regimes of the
      growth catalyst in order to define growth boundaries. Here, we present a chemical
      dynamic basis for this threshold, in which feedback between two pattern-forming
      mechanisms controls the extent of the regions in which fast growth occurs. This
      provides a general self-contained mechanism for growth control in plant
      morphogenesis (not relying on external cues) which can account for both simple
      tip extension and symmetry-breaking branching phenomena.

PMID- 22483849
TI  - Getting a sense for signals: regulation of the plant iron deficiency response.
AB  - Understanding the Fe deficiency response in plants is necessary for improving
      both plant health and the human diet, which relies on Fe from plant sources. In
      this review we focus on the regulation of the two major strategies for iron
      acquisition in plants, exemplified by the model plants Arabidopsis and rice.
      Critical to our knowledge of Fe homeostasis in plants is determining how Fe is
      sensed and how this signal is transmitted and integrated into a response. We will
      explore the evidence for an Fe sensor in plants and summarize the recent findings
      on hormones and signaling molecules which contribute to the Fe deficiency
      response. This article is part of a Special Issue entitled: Cell Biology of
      Metals.

PMID- 22483852
TI  - Over-expression of Hlx homeobox gene in DC2.4 dendritic cell enhances its
      maturation and antigen presentation.
AB  - Hlx as a Th1-specific transcription factor, it appears to drive maturation of Th1
      and IFN-gamma secretion in cooperation with T-bet. In this study, we established
      a stable Hlx-over-expressed dendritic cell line (DC2.4/Hlx), and investigated the
      possible effect of Hlx gene on maturation of dendritic cell-line (DC2.4). Results
      shown that over-expressed Hlx in DC2.4 up-regulated the transcription and
      expression of IFN-gamma, increased the expression of maturation makers including
      CD40, CD80, CD86, MHC-I and MHC-II. Functional assay for DC2.4/Hlx showed that
      over-expressed Hlx increased the expression level of interleukin-12 in the
      supernatant and decreased DC endocytosis when cells were incubated in vitro.
      Furthermore, using a syngeneic T cell activation model, we found that DC2.4/Hlx
      could obviously present ovalbumin (OVA) antigen to T cell in OVA pre-immunized
      mice.

PMID- 22483854
TI  - Myasthenia gravis appearing 18 years after resection of benign thymoma with
      subsequent limbic encephalitis.
AB  - Thymoma is associated with multiple autoimmune disorders, most commonly
      myasthenia gravis (MG). However, symptomatic MG may first present following
      thymectomy. We report an unusual patient with paraneoplastic limbic encephalitis
      diagnosed a few months after total thymectomy for asymptomatic thymoma, followed
      18 years later by the onset of symptomatic MG without evidence of tumor
      recurrence.

PMID- 22483853
TI  - Decreased hippocampal expression of calbindin D28K and cognitive impairment in
      MELAS.
AB  - Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS) is a maternally inherited mitochondrial syndrome characterized by
      seizures, migrainous headaches, lactic acidosis, vomiting, and recurrent stroke
      like episodes. Patients often suffer from cognitive dysfunction of unclear
      pathogenesis. In this study, we explored a possible link between cognitive
      dysfunction and hippocampal expression of calbindin D(28KD) (CB), a high affinity
      calcium-binding protein, in four MELAS patients, using post mortem hippocampal
      tissues. We found significantly reduced CB levels in all patients by
      immunohistochemistry, Western blot, and quantitative real-time PCR. Reduction in
      CB expression has been associated with aging and with neurodegenerative
      disorders, including Alzheimer's disease. We postulate that the reduced CB
      expression may play a role in the cognitive abnormalities associated with MELAS.

PMID- 22483855
TI  - Impact of free ammonia on anammox rates (anoxic ammonium oxidation) in a moving
      bed biofilm reactor.
AB  - Using a bench scale moving bed bioreactor (MBBR), the effect of free ammonia (FA,
      NH(3), the un-ionized form of ammonium NH(4)(+)) concentration on anoxic ammonium
      oxidation (anammox) was evaluated based on the volumetric nitrogen removal rate
      (NRR). Although, a detailed microbial analysis was not conducted, the major NRR
      observed was assumed to be by anammox, based on the nitrogen conversion ratios of
      nitrite to ammonium and nitrate to ammonium. Since the concentration of free
      ammonia as a proportion of the total ammonia concentration is pH-dependent, the
      impact of changing the operating pH from 6.9 to 8.2, was investigated under
      constant nitrogen loading conditions during continuous reactor operation.
      Furthermore, the effect of sudden nitrogen load changes was investigated under
      constant pH conditions. Batch tests were conducted to determine the immediate
      response of the anammox consortium to shifts in pH and FA concentrations. It was
      found that FA was inhibiting NRR at concentrations exceeding 2 mg N L(-1). In the
      pH range 7-8, the decrease in anammox activity was independent of pH and related
      only to the concentration of FA. Nitrite concentrations of up to 120 mg N L(-1)
      did not negatively affect NRR for up to 3.5 h. It was concluded that a stable NRR
      in a moving bed biofilm reactor depended on maintaining FA concentrations below 2
      mg N L(-1) when the pH was maintained between 7 and 8.

PMID- 22483856
TI  - Dissolution kinetics of sub-millimeter Composition B detonation residues: role of
      particle size and particle wetting.
AB  - The dissolution of the 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro
      1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX)
      from microscale particles (<250MUm) of the explosive formulation Composition B
      was examined and compared to dissolution from macroscopic particles (>0.5mm). The
      dissolution of explosives from detonation soot was also examined. The measured
      mass transfer coefficients for the microscale particles were one to two orders of
      magnitude greater than the macroscopic particles. When normalized to particle
      surface area, mass transfer coefficients of microscale and macroscale particles
      were similar, indicating that the bulk dissolution processes were similar
      throughout the examined size range. However, an inverse relationship was observed
      between the particle diameter and the RDX:TNT mass transfer rate coefficient
      ratio for dry-attritted particles, which suggests that RDX may be more readily
      dissolved (relative to TNT) in microscale particles compared to macroscale
      particles. Aqueous weathering of larger Composition B residues generated
      particles that possessed mass transfer coefficients that were on the order of 5-
      to 20-fold higher than dry-attritted particles of all sizes, even when normalized
      to particle surface area. These aqueous weathered particles also possessed a
      fourfold lower absolute zeta-potential than dry-attritted particles, which is
      indicative that they were less hydrophobic (and hence, more wettable) than dry
      attritted particles. The increased wettability of these particles provides a
      plausible explanation for the observed enhanced dissolution. The wetting history
      and the processes by which particles are produced (e.g., dry physical attrition
      vs. aqueous weathering) of Composition B residues should be considered when
      calculating mass transfer rates for fate and transport modeling.

PMID- 22483857
TI  - Insights into the pathophysiology of the antiphospholipid syndrome provided by
      atomic force microscopy.
AB  - The antiphospholipid syndrome (APS) is an enigmatic autoimmune disorder in which
      patients present with thrombosis and/or recurrent pregnancy losses together with
      laboratory evidence for the presence of autoantibodies in the blood that
      recognize proteins that bind to anionic phospholipids - the most important of
      which is beta(2)-glycoprotein I (beta(2)GPI). Earlier, we hypothesized that the
      clinical manifestations arise from antibody-induced disruption of a two
      dimensional anticoagulant crystal shield, composed of annexin A5, present on
      placental trophoblast plasma membranes. Accordingly, we reasoned that a high
      resolution imaging technology, such as atomic force microscopy could be used to
      investigate such molecular interactions at high resolution in a non-fixed
      hydrated environment. This review will focus on the contribution of this
      technique to the elucidation of the mechanism of APS.

PMID- 22483859
TI  - Efficacy and safety of self-expandable metal stents for biliary decompression in
      patients receiving neoadjuvant therapy for pancreatic cancer: a prospective
      study.
AB  - BACKGROUND: Increasing numbers of patients with resectable pancreatic cancer are
      receiving neoadjuvant therapy. Biliary drainage with plastic stents during this
      period can be associated with recurrent episodes of stent occlusion resulting in
      unplanned ERCPs and interruptions in therapy. OBJECTIVE: To evaluate the efficacy
      and safety of self-expandable metal stents (SEMSs) during the neoadjuvant period
      for resectable pancreatic cancer. DESIGN: Patients with proven pancreatic
      adenocarcinoma with biliary obstruction underwent placement of SEMSs, and data on
      stent patency and complication rates were collected prospectively. SETTING:
      Tertiary-care referral center. PATIENTS: This study involved 55 patients with
      resectable and borderline resectable pancreatic duct adenocarcinoma who were
      recruited between March 2009 and December 2010. INTERVENTION: SEMSs were placed
      for biliary decompression. The shortest length of stent required to bridge the
      stricture was used so as to leave enough of the normal bile duct above the stent
      available for subsequent surgical anastomosis. Endoscopic reintervention was
      performed in those with stent malfunction. Stents were not removed before
      surgery. MAIN OUTCOME MEASUREMENTS: Stent patency rate during the neoadjuvant
      period, stent malfunction rate, and complication rates. Information on stent
      related difficulties, if any, during surgery. RESULTS: Fifty-five patients were
      recruited (29 men, 26 women; age, mean [+/- SD] 65.9 +/- 11 years; resectable 23,
      borderline resectable 32). Median time for neoadjuvant therapy and restaging
      before surgery was 104 days (range 70-260 days). At the median time of 104 days,
      88% of SEMSs remained patent. By 260 days, stent malfunction occurred in 15% of
      patients. These included stent occlusion in 13% and stent migration in 2%. SEMS
      malfunction occurred in 3 of 27 patients (11%) who ultimately underwent
      pancreaticoduodenectomy and in 5 of 21 patients (24%) with disease progression (P
      = not significant). The presence of SEMSs did not interfere with
      pancreaticoduodenectomy in any patients who underwent surgery. LIMITATIONS:
      Nonrandomized study. CONCLUSION: SEMSs are effective and safe in achieving
      durable biliary drainage in patients with pancreatic cancer receiving neoadjuvant
      therapy. It is not necessary to remove SEMSs before surgery if the shortest
      length of stent required to bridge the stricture is used.

PMID- 22483860
TI  - Tooth extraction in patients on zoledronic acid therapy.
AB  - OBJECTIVES: Surgical management of patients following zoledronic acid therapy is
      particularly difficult, since the dental extraction is the main cause of BRONJ.
      METHODS: A case-control study was conducted on 176 patients treated with
      intravenous (IV) bisphosphonates for oncologic pathologies who also underwent
      dental extractions. The study was divided randomly into two groups: 91 were
      treated with Plasma Rich in Growth Factor Plasma (PRGF) (study group) and the
      other 85 were not treated with the growth factor preparation (control group).
      RESULTS: Panoramic X-ray and computed tomography were performed both before and
      60 months after surgery. By clinical and radiological diagnosis, BRONJ was
      diagnosed in only 5 patients in the control group at an average of 91, 6 days
      after tooth extraction. CONCLUSIONS: We hypothesize that Plasma Rich in Growth
      Factor (PRGF) is important for the successful treatment of patients on
      bisphosphonates to restore the osteoblast/osteoclast homeostatic cycles via
      autologous cytokines. Moreover, this protocol reduces the risk of BRONJ when it
      is necessary to perform dental extractions in patients undergoing IV
      bisphosphonate treatment.

PMID- 22483861
TI  - Trends in salivary diagnostics - a 5-year review of oral oncology (2007-2011).

PMID- 22483862
TI  - Simplified open repair for anterior chest wall deformities. Analysis of results
      in 205 patients.
AB  - INTRODUCTION: Pectus deformities are the most frequently seen congenital thoracic
      wall anomalies. The cause of these conditions is thought to be abnormal
      elongation of the rib cartilages. We here report our clinical experience and the
      results of a sternochondroplasty procedure based on the subperichondrial
      resection of the elongated cartilages. HYPOTHESIS: This technique is a valuable
      surgical strategy to treat the wide variety of pectus deformities. PATIENTS AND
      METHODS: During the period from October 2001 through September 2009, 205 adult
      patients (171 men and 34 women) underwent pectus excavatum (181), carinatum (19)
      or arcuatum (5) repair. The patients' pre and postoperative data were collected
      using a computerized database, and the results were assessed with a minimum 2
      year follow-up. RESULTS: The postoperative morbidity rate was minimal and the
      mortality was nil. The surgeon graded cosmetic results as excellent (72.5%), good
      (25%) or fair (2.5%), while patients reported better results. Patients with
      pectus excavatum were found to have much more patent foramen ovale (PFO) than the
      normal adult population, which occluded after the procedure in 61% of patients,
      and significant improvement was found in exercise cardiopulmonary function and
      exercise tolerance at the 1-year follow-up. DISCUSSION: Our sternochondroplasty
      technique based on the subperichondrial resection of the elongated cartilages
      allows satisfactory repair of both pectus excavatum and sternal prominence. It is
      a safe procedure that might improve the effectiveness of surgical therapy in
      patients with pectus deformities.

PMID- 22483863
TI  - Malignant fibrous histiocytoma of the spermatic cord in a patient with polycystic
      kidney disease; review of the literature.

PMID- 22483864
TI  - Familial Lund frontotemporal dementia caused by C9ORF72 hexanucleotide expansion.
AB  - Frontotemporal dementia (FTD) as an important clinical entity was rediscovered in
      Lund and Manchester in the early 1990s. Here we show that the large Lund pedigree
      with behavioral variant of frontotemporal dementia previously described with this
      disorder has an expansion in the recently described C9ORF72 locus on chromosome
      9.

PMID- 22483865
TI  - Strikingly different properties of uracil-DNA glycosylases UNG2 and SMUG1 may
      explain divergent roles in processing of genomic uracil.
AB  - Genomic uracil resulting from spontaneously deaminated cytosine generates
      mutagenic U:G mismatches that are usually corrected by error-free base excision
      repair (BER). However, in B-cells, activation-induced cytosine deaminase (AID)
      generates U:G mismatches in hot-spot sequences at Ig loci. These are subject to
      mutagenic processing during somatic hypermutation (SHM) and class switch
      recombination (CSR). Uracil N-glycosylases UNG2 and SMUG1 (single strand
      selective monofunctional uracil-DNA glycosylase 1) initiate error-free BER in
      most DNA contexts, but UNG2 is also involved in mutagenic processing of AID
      induced uracil during the antibody diversification process, the regulation of
      which is not understood. AID is strictly single strand-specific. Here we show
      that in the presence of Mg2+ and monovalent salts, human and mouse SMUG1 are
      essentially double strand-specific, whereas UNG2 efficiently removes uracil from
      both single and double stranded DNA under all tested conditions. Furthermore,
      SMUG1 and UNG2 display widely different sequence preferences. Interestingly,
      uracil in a hot-spot sequence for AID is 200-fold more efficiently removed from
      single stranded DNA by UNG2 than by SMUG1. This may explain why SMUG1, which is
      not excluded from Ig loci, is unable to replace UNG2 in antibody diversification.
      We suggest a model for mutagenic processing in which replication protein A (RPA)
      recruits UNG2 to sites of deamination and keeps DNA in a single stranded
      conformation, thus avoiding error-free BER of the deaminated cytosine.

PMID- 22483867
TI  - X-linked adrenoleukodystrophy: clinical, metabolic, genetic and
      pathophysiological aspects.
AB  - X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease.
      The two main clinical phenotypes of X-ALD are adrenomyeloneuropathy (AMN) and
      inflammatory cerebral ALD that manifests either in children or more rarely in
      adults. About 65% of heterozygote females develop symptoms by the age of 60years.
      Mutations in the ABCD1 gene affect the function of the encoded protein ALDP, an
      ATP-binding-cassette (ABC) transporter located in the peroxisomal membrane
      protein. ALDP deficiency impairs the peroxisomal beta-oxidation of very long
      chain fatty acids (VLCFA) and facilitates their further chain elongation by
      ELOVL1 resulting in accumulation of VLCFA in plasma and tissues. While all
      patients have mutations in the ABCD1 gene, there is no general genotype-phenotype
      correlation. Environmental factors and a multitude of modifying genes appear to
      determine the clinical manifestation in this monogenetic but multifactorial
      disease. This review focuses on the clinical, biochemical, genetic and
      pathophysiological aspects of X-ALD.

PMID- 22483866
TI  - The conserved Cockayne syndrome B-piggyBac fusion protein (CSB-PGBD3) affects DNA
      repair and induces both interferon-like and innate antiviral responses in CSB
      null cells.
AB  - Cockayne syndrome is a segmental progeria most often caused by mutations in the
      CSB gene encoding a SWI/SNF-like ATPase required for transcription-coupled DNA
      repair (TCR). Over 43Mya before marmosets diverged from humans, a piggyBac3
      (PGBD3) transposable element integrated into intron 5 of the CSB gene. As a
      result, primate CSB genes now generate both CSB protein and a conserved CSB-PGBD3
      fusion protein in which the first 5 exons of CSB are alternatively spliced to the
      PGBD3 transposase. Using a host cell reactivation assay, we show that the fusion
      protein inhibits TCR of oxidative damage but facilitates TCR of UV damage. We
      also show by microarray analysis that expression of the fusion protein alone in
      CSB-null UV-sensitive syndrome (UVSS) cells induces an interferon-like response
      that resembles both the innate antiviral response and the prolonged interferon
      response normally maintained by unphosphorylated STAT1 (U-STAT1); moreover, as
      might be expected based on conservation of the fusion protein, this potentially
      cytotoxic interferon-like response is largely reversed by coexpression of
      functional CSB protein. Interestingly, expression of CSB and the CSB-PGBD3 fusion
      protein together, but neither alone, upregulates the insulin growth factor
      binding protein IGFBP5 and downregulates IGFBP7, suggesting that the fusion
      protein may also confer a metabolic advantage, perhaps in the presence of DNA
      damage. Finally, we show that the fusion protein binds in vitro to members of a
      dispersed family of 900 internally deleted piggyBac elements known as MER85s,
      providing a potential mechanism by which the fusion protein could exert
      widespread effects on gene expression. Our data suggest that the CSB-PGBD3 fusion
      protein is important in both health and disease, and could play a role in
      Cockayne syndrome.

PMID- 22483868
TI  - Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal
      disorders.
AB  - Peroxisomal disorders are an important group of neurometabolic diseases. The
      clinical presentation is varied in terms of age of onset, severity, and different
      neurological symptoms. The clinical course spans from death in infancy, rapid
      functional decline, slow decline on long-term followup, to apparent stable
      course. Leukoencephalopathy and developmental anomalies are characteristic
      findings on cerebral MR imaging. From a diagnostic point of view the disorders
      can be clinically subdivided into four broad categories: (1) the Zellweger
      spectrum disorders and the peroxisomal beta-oxidation disorders, (2) the
      rhizomelic chondrodysplasia punctata spectrum disorders, (3) the X-linked
      adrenoleukodystrophy/adrenomyeloneuropathy complex and (4) the remaining
      disorders. This article discusses the role of MRI findings in the clinical
      approach of peroxisomal disorders with neurological disease.

PMID- 22483870
TI  - PBDEs in environmental samples: sampling and analysis.
AB  - The paper reviews the subject literature concerning analytical procedures
      routinely sed for monitoring polybrominated diphenyl ethers (PBDE) in
      environmental samples. It describes and summarizes subsequent stages of
      analytical procedure including sample collection and preparation, extraction,
      clean-up and final determination. Different approaches with their advantages and
      limitations are presented. Special attention is drawn to the newly developed,
      promising extraction techniques, especially: liquid-liquid-microextraction (LLME)
      with its modifications, cloud point extraction (CPE) and hollow fiber
      microextraction. The review compares available detection techniques taking into
      account their usefulness for determining different PBDEs in complex matrix as
      well as discussing possible limitations that may occur during the analysis. The
      quality assurance and quality control aspect of analytical procedure is
      described. Finally special attention is paid to the determination of highly
      brominated PBDE compounds (e.g. BDE209), which requires implementation of
      different analytical approach.

PMID- 22483869
TI  - Overexpression of VMAT-2 and DT-diaphorase protects substantia nigra-derived
      cells against aminochrome neurotoxicity.
AB  - We tested the hypothesis that both VMAT-2 and DT-diaphorase are an important
      cellular defense against aminochrome-dependent neurotoxicity during dopamine
      oxidation. A cell line with VMAT-2 and DT-diaphorase over-expressed was created.
      The transfection of RCSN-3 cells with a bicistronic plasmid coding for VMAT-2
      fused with GFP-IRES-DT-diaphorase cDNA induced a significant increase in protein
      expression of VMAT-2 (7-fold; P<0.001) and DT-diaphorase (9-fold; P<0.001),
      accompanied by a 4- and 5.5-fold significant increase in transport and enzyme
      activity, respectively. Studies with synaptic vesicles from rat substantia nigra
      revealed that VMAT-2 uptake of 3H-aminochrome 6.3 +/- 0.4nmol/min/mg was similar
      to dopamine uptake 6.2 +/- 0.3nmol/min/mg that which were dependent on ATP.
      Interestingly, aminochrome uptake was inhibited by 2MUM lobeline but not
      reserpine (1 and 10MUM). Incubation of cells overexpressing VMAT-2 and DT
      diaphorase with 20MUM aminochrome resulted in (i) a significant decrease in cell
      death (6-fold, P<0.001); (ii) normal ultra structure determined by transmission
      electron microscopy contrasting with a significant increase of autophagosome and
      a dramatic remodeling of the mitochondrial inner membrane in wild type cells;
      (iii) normal level of ATP (256 +/- 11MUM) contrasting with a significant decrease
      in wild type cells (121+/-11MUM, P<0.001); and (iv) a significant decrease in DNA
      laddering (21 +/- 8pixels, P<0.001) cells in comparison with wild type cells
      treated with 20MUM aminochrome (269 +/- 9). These results support our hypothesis
      that VMAT-2 and DT-diaphorase are an important defense system against aminochrome
      formed during dopamine oxidation.

PMID- 22483871
TI  - Speciation of challenging elements in food by atomic spectrometry.
AB  - The review addresses trends in speciation analysis of challenging - rather rarely
      examined despite their importance for human health - elements in foodstuffs with
      special attention prior to sample preparation. Elements of interest are cobalt,
      iodine, manganese, iron, zinc, copper and molybdenum belong to the group of
      elements still appealed for searching their speciation despite extremely small
      contents in foodstuffs. Advantages and weaknesses of recommended procedures are
      overviewed and discussed, highlighting state-of-the-art speciation methodologies
      developed so far in the field.

PMID- 22483872
TI  - Improvement of sensitivity of electrolyte cathode discharge atomic emission
      spectrometry (ELCAD-AES) for mercury using acetic acid medium.
AB  - A method has been developed to improve the sensitivity of the electrolyte cathode
      discharge atomic emission spectrometry (ELCAD-AES) for mercury determination.
      Effects of various low molecular weight organic solvents at different volume
      percentages as well as at different acid molarities on the mercury signal were
      investigated using ELCAD-AES. The addition of few percent of organic solvent,
      acetic acid produced significant enhancement in mercury signal. Acetic acid of 5%
      (v/v) with the 0.2M acidity has been found to give 500% enhancement for mercury
      signal in flow injection mode. Under the optimized parameters the repeatability,
      expressed as the percentage relative standard deviation of spectral peak area for
      mercury with 5% acetic acid was found to be 10% for acid blank solution and 5%
      for 20 ng/mL mercury standard based on multiple measurements with a multiple
      sample loading in flow injection mode. Limit of detection of this method was
      determined to be 2 ng/mL for inorganic mercury. The proposed method has been
      validated by determining mercury in certified reference materials, Tuna fish
      (IAEA-350) and Aquatic plant (BCR-060). Accuracy of the method for the mercury
      determination in the reference materials has been found to be between 3.5% and
      5.9%. This study enhances the utility of ELCAD-AES for various types of
      biological and environmental materials to quantify total mercury at very low
      levels.

PMID- 22483873
TI  - Highly sensitive glucose biosensor based on the effective immobilization of
      glucose oxidase/carbon-nanotube and gold nanoparticle in nafion film and
      peroxyoxalate chemiluminescence reaction of a new fluorophore.
AB  - A novel glucose biosensor based on the chemiluminescence (CL) detection of
      enzymatically generated H(2)O(2) was constructed by the effective immobilization
      of glucose oxidase (GOD)/carbon-nanotubes (CNTs)/gold nanoparticles (GNPs) in
      nafion film on graphite support. The influences of various experimental
      parameters such as solution pH, the action time of the enzyme, interferents and
      the concentration of CL reagents were investigated. Carbon nanotubes and gold
      nanoparticles offer excellent catalytic activity toward hydrogen peroxide
      generation in enzymatic reaction between glucose oxidase and glucose, which would
      enable sensitive determination of glucose. Under the optimum condition, the
      linear response range of glucose was found to be 2.25 * 10(-6) to 1.75 * 10(-4 )
      mol L(-1), and the detection limit (defined as the concentration that could be
      detected at the signal-to-noise ratio of 3) was 1.00 * 10(-6) mol L(-1). The CL
      biosensor exhibited good storage stability, i.e., 80% of its initial response was
      retained after 10 days storage at pH 7.0. The present CL biosensor has been used
      to determine the glucose concentrations in real serum and urine samples with
      satisfactory results.

PMID- 22483874
TI  - A piezoelectric immunosensor for chloramphenicol detection in food.
AB  - A piezoelectric immunosensor on the basis of electrogenerated polymer for
      detecting trace quantities of chloramphenicol, a drug which is used in veterinary
      for treatment and prevention of infectious diseases, was developed. The detection
      was conducted in a competitive format with the use of hapten-protein conjugate
      and monoclonal antibodies. The limit of detection is 0.2 ng ml(-1), the
      calibration curve is linear in the range of concentrations 0.5-100.0 ng ml(-1).
      Chloramphenicol was detected in food (meat, milk, egg, honey).

PMID- 22483875
TI  - A test strip platform based on DNA-functionalized gold nanoparticles for on-site
      detection of mercury (II) ions.
AB  - A test strip, based on DNA-functionalized gold nanoparticles for Hg(2+)
      detection, has been developed, optimized and validated. The developed
      colorimetric mercury sensor system exhibited a highly sensitive and selective
      response to mercury. The measurement principle is based on thymine-Hg(2+)-thymine
      (T-Hg(2+)-T) coordination chemistry and streptavidin-biotin interaction. A biotin
      labeled and thiolated DNA was immobilized on the gold nanoparticles (AuNPs)
      surface through a self-assembling method. Another thymine-rich DNA, which was
      introduced to form DNA duplexes on the AuNPs surface with thymine-Hg(2+)-thymine
      (T-Hg(2+)-T) coordination in the presence of Hg(2+), was immobilized on the
      nitrocellulose membrane as the test zone. When Hg(2+) ions were introduced into
      this system, they induced the two strands of DNA to intertwist by forming T
      Hg(2+)-T bonds resulting in a red line at the test zone. The biotin-labeled and
      thiolated DNA-functionalized AuNPs could be captured by streptavidin which was
      immobilized on the nitrocellulose membrane as the control zone. Under optimized
      conditions, the detection limit for Hg(2+) was 3 nM, which is lower than the
      10nM, maximum contaminant limit defined by the US Environmental Protection Agency
      (EPA) for drinking water. A parallel analysis of Hg(2+) in pool water samples
      using cold vapor atomic absorption spectrometry showed comparable results to
      those obtained from the strip test. Therefore, the results obtained in this study
      could be used as basic research for the development of Hg(2+) detection, and the
      method developed could be a potential on-site screening tool for the rapid
      detection of Hg(2+) in different water samples without special instrumentation.
      All experimental variables that influence the test strip response were optimized
      and reported.

PMID- 22483876
TI  - Optical Cu2+ probe bearing an 8-hydroxyquinoline subunit: high sensitivity and
      large fluorescence enhancement.
AB  - A new fluorescent and colorimetric probe RCu1 with ultra-sensitivity (detection
      limit is 4.7 nM (3sigma)) was developed. It is based on a rhodamine B derivative
      modified with a functionalized 8-hydroxyquinoline group as a copper-binding site
      which greatly increases the affinity for Cu(2+). Cu(2+) acts not only as a
      selective recognizing guest but also a hydrolytic promoter. RCu1 showed single
      selectively sensing Cu(2+) over other cations and much larger fluorescence
      enhancement (as high as over 1000-fold) than those based on Cu(2+)-complexation.
      The detection mechanism was proved by TOF-MS, FT-IR, (1)H NMR and Gaussian
      calculations. Based on the outstanding recognition ability of RCu1 toward Cu(2+),
      an analytical procedure was developed for Cu(2+)-determination in natural water
      samples and soil sample.

PMID- 22483877
TI  - Development of a fast capillary electrophoresis method for determination of
      carbohydrates in honey samples.
AB  - In this study, the determination of fructose, glucose and sucrose by capillary
      electrophoresis (CE) was investigated. The tendency of the analyte to undergo
      electromigration dispersion and the buffer capacity were evaluated using the
      Peakmaster((r)) software and considered in the optimization of the background
      electrolyte, which was composed of 20 mmol L(-1) sorbic acid, 0.2 mmol L(-1) CTAB
      and 40 mmol L(-1) NaOH at pH 12.2. Under optimal CE conditions, the separation of
      the substances investigated was achieved in less than 2 min. The detection limits
      for the three analytes were in the range of 0.022 and 0.029 g L(-1) and precision
      measurements within 0.62-4.69% were achieved. The proposed methodology was
      applied in the quantitative analysis by direct injection of in honey samples to
      determine the main sugars presents. The samples were previously dissolved in
      deionized water and filtered with no other sample treatment. The mean values for
      fructose, glucose and sucrose were in the ranges of 33.65-45.46 g 100g(-1), 24.63
      35.06 g 100g(-1) and <0.22-1.32 g 100g(-1), respectively. The good analytical
      performance of the method makes it suitable for implementation in food
      laboratories for the routine analysis of honey samples.

PMID- 22483878
TI  - Sensitive detection of hydroxylamine at a simple baicalin carbon nanotubes
      modified electrode.
AB  - A baicalin multi-wall carbon nanotubes (BaMWCNT) modified glassy carbon electrode
      (GCE) for the sensitive determination of hydroxylamine was described. The
      BaMWCNT/GCE with dramatic stability was firstly fabricated with a simple
      adsorption method. And it showed excellent catalytic activity toward the
      electrooxidation of hydroxylamine. The amperometric response at the BaMWCNT/GCE
      modified electrode increased linearly to hydroxylamine concentrations in the
      range of 0.5 MUM to 0.4mM with a detection limit of 0.1 MUM. The modified
      electrode was applied to detection hydroxylamine in the tap water, and the
      average recovery for the standards added was 96.0%.

PMID- 22483879
TI  - Artificial neural networks combined with experimental design: a "soft" approach
      for chemical kinetics.
AB  - The possibilities of artificial neural networks (ANNs) "soft" computing to
      evaluate chemical kinetic data have been studied. In the first stage, a set of
      "standard" kinetic curves with known parameters (rate constants and/or
      concentrations of the reactants), which is some kind of "normalized maps", is
      prepared. The database should be built according to a suitable experimental
      design (ED). In the second stage, such data set is then used for ANNs "learning".
      Afterwards, in the second stage, experimental data are evaluated and parameters
      of "other" kinetic curves are computed without solving anymore the system of
      differential equations. The combined ED-ANNs approach has been applied to solve
      several kinetic systems. It was also demonstrated that using ANNs, the
      optimization of complex chemical systems can be achieved even not knowing or
      determining the values of the rate constants. Moreover, the solution of
      differential equations is here not necessary, as well. Using ED the number of
      experiments can be reduced substantially. Methodology of ED-ANNs applied to
      multicomponent analysis shows advantages over classical methods while the
      knowledge of kinetic reactions is not needed. ANNs computation in kinetics is
      robust as shown evaluating the effect of experimental errors and it is of general
      applicability.

PMID- 22483880
TI  - Simultaneous determination of L-ascorbic acid, dopamine and uric acid with gold
      nanoparticles-beta-cyclodextrin-graphene-modified electrode by square wave
      voltammetry.
AB  - Graphene decorated with gold nanoparticles (AuNPs-beta-CD-Gra) has been
      synthesized by in situ thermal reduction of graphene oxide and HAuCl(4) with beta
      cyclodextrin (beta-CD) under alkaline condition. The AuNPs-beta-CD-Gra product
      was well characterized by infrared spectroscopy, X-ray powder diffraction,
      scanning electron microscopy, high-resolution transmission electron microscopy,
      and selected area electron diffraction. This material was used to fabricate an
      AuNPs-beta-CD-Gra-modified glassy carbon electrode (GCE) which showed excellent
      electro-oxidation of l-ascorbic acid (AA), dopamine (DA) and uric acid (UA) in
      0.10 M NaH(2)PO(4)-HCl buffer solution (pH 2.0) by square wave voltammetry (SWV).
      Three well-resolved oxidation peaks of AA and DA and UA were obtained. The AuNPs
      beta-CD-Gra/GCE exhibits linear responses to AA, DA and UA in the ranges 30-2000,
      0.5-150 and 0.5-60 MUM, respectively. The detection limits (based on S/N=3 and
      preconcentration time=3.0 min) for AA, DA and UA are 10, 0.15 and 0.21 MUM,
      respectively. The AuNPs-beta-CD-Gra/GCE has been successfully applied to
      determine UA in human urine with satisfactory results. Our work provides a
      simple, convenient and green route to synthesize AuNPs on Gra which is
      potentially useful in electroanalysis.

PMID- 22483881
TI  - Reverse flow injection analysis method for catalytic spectrophotometric
      determination of iron in estuarine and coastal waters: a comparison with normal
      flow injection analysis.
AB  - A method for determining iron in seawater had been developed by coupling reverse
      flow injection analysis (rFIA) and catalytic spectrophotometric detection with
      N,N-dimethyl-p-phenylenediamine dihydrochloride (DPD). With a seawater sample or
      a standard solution as the carrier, the mixture of DPD and buffer was injected
      into the carrier stream quantitatively and discretely. After mixing with
      H(2)O(2), the DPD was oxidized to form two pink semiquinone derivatives that were
      monitored at 514 nm wavelength with a reference at 700 nm. The method detection
      limit was 0.40 nmol L(-1), lower than half of that of normal flow injection
      analysis (nFIA) method. The sample throughput was 10h(-1) with triplicate
      determination, compared with 4h(-1) for nFIA-DPD method. The analysis results of
      the certified seawaters CASS-4 (12.33 +/- 0.18 nmol L(-1)) and NASS-5 (3.47 +/-
      0.23 nmol L(-1)) well agreed with the certified values (12.77 +/- 1.04 and 3.71
      +/- 0.63 nmol L(-1), respectively). The typical precision of the method for a
      2.97 nmol L(-1) iron sample was 4.49% (n=8). Interferences from copper and
      salinity were investigated. An instrument was assembled based on the proposed
      method and applied successfully to analyze total dissolvable iron (TDFe) in
      surface seawater samples collected from the Pearl River Estuary, the results of
      which revealed non-conservative behavior of TDFe during the estuarine mixing.
      Results for these samples with both rFIA-DPD and nFIA-DPD methods showed good
      agreement with each other. The proposed method was superior to the currently used
      nFIA-DPD method, particularly when it is adapted for field and in situ
      deployment, due to its lower reagent consumption, higher sample throughput and
      keeping the manifold tubing clean.

PMID- 22483882
TI  - A portable Raman sensor for the rapid discrimination of olives according to fruit
      quality.
AB  - In the real marketplace, providing high-quality olive oil is important from the
      perspective of both consumers and producers. Quality control should meet all
      requirements in the production process, from farm to packaging. The quality of
      olive oil can be affected by several factors, including agricultural techniques,
      seasonal conditions, farming systems, maturity, method and duration of storage,
      and process technology. The quality of oil produced also depends largely on the
      quality of the olives. In an enterprise aimed at producing high-quality oils,
      olives with defects ('ground'; i.e., fallen to the ground) should be separated
      from healthy fruit ('sound'; i.e., collected directly from the tree), because a
      very small portion of low-quality fruit can ruin the whole batch. The fruit falls
      partly because of its maturation process, but also because of pest and disease
      attack or weather conditions (strong wind). Fruit that has fallen to the ground
      can suffer a rapid deterioration in quality. Currently, the separation of fruits
      is based mainly on visual inspection or information provided by the farmer. These
      are not very reliable procedures. Methods using analytical parameters to
      characterize the oil, such as acidity and peroxide value, can be applied, but
      they require a lot of time and materials. Alternative techniques are therefore
      needed for the rapid and inexpensive discrimination of olives as part of a
      quality control strategy. The work described here aims to determine the potential
      of low-resolution Raman spectroscopy for the discrimination of olives before the
      oil processing stage in order to detect whether they have been collected directly
      from the tree (i.e., healthy fruit) or not. Low-resolution Raman spectroscopy was
      applied together with multivariate procedures to achieve this aim. PCA was used
      to find natural clusters in the data. Supervised classification methods were then
      applied: Soft Independent Modeling of Class Analogy (SIMCA), PLS Discriminate
      Analysis (PLS-DA) and K-nearest neighbors (KNN). The best results were obtained
      using the KNN method, with prediction abilities of 100% for 'sound' and 97% for
      'ground' in an independent validation set. These results demonstrated the
      potential of a portable Raman instrument for detecting good quality olives before
      the oil processing stage, by developing models that could be applied before this
      stage, thus contributing to an overall improvement in quality control.

PMID- 22483883
TI  - Evaluation of new mixed-mode UHPLC stationary phases and the importance of
      stationary phase choice when using low ionic-strength mobile phase additives.
AB  - In this study, the selectivity, retention properties, peak shape and loading
      capacity for bases were practically evaluated using two UHPLC mixed-mode hybrid
      CSH stationary phases modified by C18 or Phenyl group. The data were compared
      with the data obtained on other UHPLC hybrid stationary phases (BEH C18, BEH C8,
      BEH Phenyl and BEH Shield RP18) at both basic and acidic conditions using
      conventional HPLC buffers (50mM ammonium formate/acetate) as well as low ionic
      strength additives such as, e.g. 0.1-0.01% formic/acetic acid and 1mM solution of
      ammonium formate/acetate, which are widely used in LC-MS applications. Ten
      pharmaceutically important compounds encompassing acids, bases and neutral were
      included into the study. Due to properties of CSH sorbent (which possess
      positively charged surface besides RP group), much improved peak shapes and
      weaker retention was obtained for bases even at very low concentration of acidic
      additives. Such conditions are ideally suited for LC-MS analysis of bases, where
      typical RP chromatographic separation (retention and good selectivity at basic
      pH) and LS-MS conditions (efficient ionization at acidic pH) are not in
      agreement. On the other hand, acids were more strongly retained and for some
      compounds the peak shape was influenced negatively due to ion-exchange mechanism.
      Further, the behavior of acidic, basic and neutral solutes is discussed using
      various additives at both basic and acidic pH for all above stated columns. The
      robustness of retention times after pH change from basic to acidic was also
      evaluated. The new CSH stationary phases represent an interesting selectivity
      tool preferably for separation of basic compounds.

PMID- 22483884
TI  - Compact optoelectronic flow-through device for fluorometric determination of
      calcium ions.
AB  - A low-cost and compact complete fluorometric detector dedicated for measurements
      under conditions of flow injection analysis has been developed. This device is
      fabricated by integration of light emitting diodes (LEDs) applied in the double
      role: as the source of light inducing fluorescence and as the detector of light
      emitted by excited fluorescent analyte. The device is made of three LEDs only,
      without any additional fibers, filters and lenses. The LEDs are integrated in the
      form of flow cell of 0.060 mL internal volume. The developed detector has been
      tested in simple flow injection manifold dedicated for fluorometric determination
      of calcium using calcein method. The system offers sensitive and selective
      determination of calcium at ppm levels with relatively high flow throughput (near
      60 injections per hour) and satisfactory reproducibility. The practical utility
      of developed detector has been confirmed by its application for analysis of
      mineral waters, medicines as well as physiological fluids.

PMID- 22483885
TI  - Simplified and miniaturized procedure based on ultrasound-assisted cytosol
      preparation for the determination of Cd and Cu bound to metallothioneins in
      mussel tissue by ICP-MS.
AB  - A simplified and miniaturized procedure for the determination of Cd and Cu bound
      to metallothioneins (MTs) by ICP-MS in mussel tissue has been developed. Cytosol
      preparation was based on the indirect sonication of slurries containing the
      lyophilized sample dispersed in 1 mL of extractant by means of a sonoreactor Cup
      Horn. Rabbit liver MTs (Apo-MT-I, Apo-MT-II and Cd(7)-MT-II) and a conventional
      cytosol preparation procedure were used for validation purposes. The usual
      heating step and additional centrifugations of the conventional procedure for
      cytosol preparation can be omitted when using ultrasound treatment. The possible
      effect of denaturation on MTs and its effect on the metal bound to MTs were
      evaluated. Variables influencing the ultrasound-assisted cytosol preparation
      procedure were carefully optimized for simultaneous determination of both metals.
      Chromatographic conditions to separate the MT fraction from other proteins
      present in cytosols were also studied. Six samples can be processed within 3 min
      of sonication. An acid ultrasound-assisted extraction procedure with diluted acid
      was also proposed for determining total Cd and Cu. Finally, Cd and Cu bound to
      MTs as well as total Cd and Cu were determined in mussels from Pontevedra and
      Ares-Betanzos coastal inlets (Galicia, Spain).

PMID- 22483886
TI  - New approaches to extraction techniques in determination of 4,4'-methylenebis(2
      chloroaniline) in air and water solutions.
AB  - Extraction techniques for 4,4'-methylenebis(2-chloroaniline) (MOCA) in air
      samples and water solutions were developed and compared. Classic techniques for
      air sampling of MOCA were enhanced by incorporating a derivatization step (3,5
      dinitrobenzoyl chloride solution in toluene), thus increasing the limit of
      detection and limit of quantification. Sampling of MOCA from water solution was
      performed using novel nanoporous polymeric (polypyrrole and polythiophene) fiber
      coatings and solid phase microextraction. Samples were analyzed by high
      performance liquid chromatography coupled with a UV detector. Using the modified
      method for air sampling of MOCA, we found that the limit of detection was 7.90 ng
      m(-3) and the limit of quantification was 23.8 ng m(-3). In contrast, the limit
      of detection for MOCA in water samples was 11.26 ng mL(-1) (polypyrrole) and
      84.62 ng mL(-1) (polythiophene) and the limit of quantification for MOCA was from
      33.78 (polypyrrole) and 253.86 ng mL(-1) (polythiophene). Correlation
      coefficients were 0.9997 for air and 0.8790-0.9852 for water samples,
      respectively. The techniques presented provide alternative methods for the
      determination of MOCA in air samples and in water solutions that are more
      sensitive, quicker and less expensive than previously established procedures.

PMID- 22483887
TI  - Polymer modified glassy carbon electrode for the electrochemical determination of
      caffeine in coffee.
AB  - 4-Amino-3-hydroxynaphthalene sulfonic acid (AHNSA) was electropolymerized on a
      glassy carbon electrode. The deposited film showed electrocatalytic activity
      towards the oxidation of caffeine. The polymer-modified electrode showed high
      sensitivity, selectivity and stability in the determination of caffeine in
      coffee. The peak current increased linearly with the concentration of caffeine in
      the range of 6 * 10(-8) to 4 * 10(-5) mol L(-1), with a detection limit of 1.37 *
      10(-7) mol L(-1) (LoD = 3delta/slope). Analysis of caffeine in coffee was
      affected neither by sample matrices nor by structurally similar compounds.
      Recoveries ranging between 93.75 +/- 2.32 and 100.75 +/- 3.32 were achieved from
      coffee extracts indicating the applicability of the developed method for real
      sample analyses.

PMID- 22483888
TI  - Detection of adulteration in hydrated ethyl alcohol fuel using infrared
      spectroscopy and supervised pattern recognition methods.
AB  - This paper proposes an analytical method to detect adulteration of hydrated ethyl
      alcohol fuel based on near infrared (NIR) and middle infrared (MIR)
      spectroscopies associated with supervised pattern recognition methods. For this
      purpose, linear discriminant analysis (LDA) was employed to build a
      classification model on the basis of a reduced subset of wavenumbers. For
      variable selection, three techniques are considered, namely the successive
      projection algorithm (SPA), the genetic algorithm (GA) and a stepwise formulation
      (SW). For comparison, models based on partial least squares discriminant analysis
      (PLS-DA) were also employed using full-spectrum. The method was validated in a
      case study involving the classification of 181 hydrated ethyl alcohol fuel
      samples, which were divided into three different classes: (1) authentic samples;
      (2) samples adulterated with water and (3) samples contaminated with methanol.
      LDA/GA and PLS-DA models were found to be the best methods for classifying the
      spectral data obtained in NIR region, which achieved a correct prediction rate of
      100% in the test set, while the LDA/SPA and LDA/SW were correctly classified at
      84.4% and 97.8%, respectively. For MIR data, all models (PLS-DA and LDA coupled
      with the SW, SPA and GA) employed in this study correctly classified all samples
      in the test set.

PMID- 22483889
TI  - A rapid method for the determination of honey diastase activity.
AB  - A new rapid method for the determination of honey diastase activity using direct
      potentiometric principles has been proposed. A platinum redox sensor has been
      used to quantify the amount of free triiodide released from a starch triiodide
      complex after starch hydrolysis by honey diastase. The method was tested on honey
      samples with varying diastase activities. The first 5 min of data for each sample
      were used for linear regression analysis in order to calculate diastase activity.
      The new method was compared with classical Schade and commercial Phadebas
      procedures. The results showed good correlations with both methods and offered a
      simple method for unit conversion to DN units for diastase activity, making the
      method suitable for routine analysis.

PMID- 22483890
TI  - Macroporous methacrylate-based monoliths as platforms for DNA microarrays.
AB  - Macroporous monoliths with different surface functionalization (reactive groups)
      were utilized as platforms for DNA analysis in microarray format. The slides
      based on a copolymer glycidyl methacrylate-co-ethylene dimethacrylate (GMA-EDMA)
      have been chosen as well known and thoroughly studied standard. In particular,
      this material has been used at optimization of DNA microanalytical procedure. The
      concentration and pH of spotting solution, immobilization temperature and time,
      blocking agent and coupling reaction duration were selected as varied parameters.
      The efficiency of analysis performed on 3-D monolithic platforms was compared to
      that established for commercially available glass slides. As a practical example,
      a diagnostic test for detection of CFTR gene mutation was carried out.
      Additionally, the part of presented work was devoted to preparation of aptamer
      based test-system that allowed successful and highly sensitive detection both of
      DNA and protein.

PMID- 22483891
TI  - Rapid sample preparation procedure for determination of retinol and alpha
      tocopherol in human breast milk.
AB  - The liposoluble vitamins (retinol and alpha-tocopherol) concentration in human
      breast milk is of a cardinal knowledge especially for nutrition of prematurely
      born. It enables the feeding optimization of these important micronutrients for
      preterm infants. The novel rapid liquid-liquid extraction procedure for human
      breast milk investigation was developed and validated according to FDA
      guidelines. The recovery of retinol was 82-90% measured at three concentration
      levels 1.0, 2.5 and 5.0 MUmol/L, for alpha-tocopherol 92-109% at concentration
      levels 2.5, 5.0 and 10.0 MUmol/L. The repeatability of extraction procedure
      expressed as relative standard deviation was 3.26% for retinol and 4.79% for
      alpha-tocopherol. Developed extraction procedure was applied on 120 human breast
      milk samples. The separation of vitamins was completed using advantages of a
      monolithic column which accomplished demands of acceleration made by modern bio
      analytical HPLC methodology. The analytes of interest were detected by diode
      array detector at wavelengths 325 nm for retinol and 290 nm for alpha-tocopherol.

PMID- 22483892
TI  - Molecular weight distribution of polysaccharides from edible seaweeds by high
      performance size-exclusion chromatography (HPSEC).
AB  - Biological properties of polysaccharides from seaweeds are related to their
      composition and structure. Many factors such as the kind of sugar, type of
      linkage or sulfate content of algal biopolymers exert an influence in the
      relationship between structure and function. Besides, the molecular weight (MW)
      also plays an important role. Thus, a simple, reliable and fast HPSEC method with
      refractive index detection was developed and optimized for the MW estimation of
      soluble algal polysaccharides. Chromatogram shape and repeatability of retention
      time was considerably improved when sodium nitrate was used instead of ultrapure
      water as mobile phase. Pullulan and dextran standards of different MW were used
      for method calibration and validation. Also, main polysaccharide standards from
      brown (alginate, fucoidan, laminaran) and red seaweeds (kappa- and iota
      carrageenan) were used for quantification and method precision and accuracy.
      Relative standard deviation (RSD) of repeatability for retention time, peak areas
      and inter-day precision was below 0.7%, 2.5% and 2.6%, respectively, which
      indicated good repeatability and precision. Recoveries (96.3-109.8%) also showed
      its fairly good accuracy. Regarding linearity, main polysaccharide standards from
      brown or red seaweeds showed a highly satisfactory correlation coefficient
      (r>0.999). Moreover, a good sensitivity was shown, with corresponding limits of
      detection and quantitation in mg/mL of 0.05-0.21 and 0.16-0.31, respectively. The
      method was applied to the MW estimation of standard algal polysaccharides, as
      well as to the soluble polysaccharide fractions from the brown seaweed Saccharina
      latissima and the red Mastocarpus stellatus, respectively. Although distribution
      of molecular weight was broad, the good repeatability for retention time provided
      a good precision in MW estimation of polysaccharides. Water- and alkali-soluble
      fractions from S. latissima ranged from very high (>2400 kDa) to low MW compounds
      (<6 kDa); this high heterogeneity could be attributable to the complex
      polysaccharide composition of brown algae. Regarding M. stellatus, sulfated
      galactans followed a descending order of MW (>1400 kDa to <10 kDa), related to
      the different solubility of carrageenans in red seaweeds. In summary, the method
      developed allows for the molecular weight analysis of seaweed polysaccharides
      with very good precision, accuracy, linearity and sensitivity within a short
      time.

PMID- 22483893
TI  - Amino acid side chain-like surface modification on magnetic nanoparticles for
      highly efficient separation of mixed proteins.
AB  - This work reports on the realization of specific functionalized silica-coated
      magnetic nanoparticles (Si-MNPs) for effective protein separation through surface
      modification with various amino acid side chain-like functional groups such as
      thiol (-SH), disulfide (-S-S-), carbon chain (-C(n)), carboxyl (-COOH), amine (
      NH(2)), and aldehyde (-CHO). This study also suggests an improved and convenient
      method for the synthesis of functionalized Si-MNPs by hydrolysis condensation
      with silan-coupling agents. The protein adsorption effects in a coexistent mixed
      state are explored using various proteins, which have different isoelectric point
      (pI) values and molecular weights, in order to elucidate the binding performance
      of different proteins one solution. The adsorption efficiency of bovine serum
      albumin (BSA; 66 kDa; pI=4.65) and lysozyme (LYZ; 14.3 kDa; pI=11) is 70-100%
      with various amino acid side chain-like functional groups. However, the
      adsorption efficiency of a mixed protein solution of BSA and LYZ was different.
      Although the relatively bulky BSA molecule displayed 50% and 20% adsorption
      corresponding to pH 4.65, and pH 11, respectively, the smaller LYZ provided
      almost 100% adsorption at both pH 4.65 and pH 11.

PMID- 22483894
TI  - Extracting genomic DNA of foodstuff by polyamidoamine (PAMAM)-magnetite
      nanoparticles.
AB  - Although genetically modified (GM) food is becoming increasingly available,
      consumers are showing a growing awareness about the need to identify GM and non
      GM foodstuff: the reliable identification of GM/non-GM food is therefore an
      important tool in the social, health and safety debates. The present research
      responds to this need (i) through developing a novel "single-pot" preparation of
      PAMAM magnetite nanoparticles (PMNPs) and by fully defining their specific
      characteristics; (ii) by demonstrating the capability of the PMNPs to isolate
      genomic DNA from different sample foods; and (iii) by experimentally
      demonstrating the identification of the isolated DNA by gel-electrophoresis, thus
      being capable of screening GM and non-GM food.

PMID- 22483895
TI  - Preparation of molecular imprinted polymers using bi-functional monomer and bi
      crosslinker for solid-phase extraction of rutin.
AB  - Molecular imprinted polymers (MIPs) were prepared using rutin as the template,
      different reagents as the functional monomer and different reagents as the cross
      linker by solution polymerization. Several parameters that would influence the
      performance of MIPs were investigated including the type of functional monomer
      (single or double) and cross-linker (single or double), and the molar ratio of
      the template, the functional monomer and the cross-linker. The optimum synthesis
      conditions of MIPs were found to be bi-monomers (acrylamide-co-2-vinyl pyridine,
      3:1) and bi-crosslinker (ethylene glycol dimethacrylate-co-divinylbenzene, 3:1).
      The ratio of the template, the functional monomer and the cross-linker was found
      to be 1:6:20. MIPs synthesized under these conditions were filled into the
      cartridges as the adsorbents of solid-phase extraction (SPE). A competition test
      was conducted to authenticate the selectivity and the specificity of molecularly
      imprinted solid-phase extraction (MISPE) for rutin using the mixture solution of
      standard rutin and its structural analogs including quercetin, naringenin and
      kaempferol. Compared with purchased SPE including C(18), silica and PCX, MISPE
      showed better selectivity and enrichment property for rutin in the extracted
      solutions of Chinese medicinal plants than any others. The mean recoveries were
      85.93% (RSD: 3.04%, n=3) for Saururus chinensis (Lour.) Bail and 88.61% (RSD:
      3.36%, n=3) for Flos Sophorae, respectively, which indicated that the optimized
      rutin-MIPs possess the value of practical application.

PMID- 22483896
TI  - Rapid and highly sensitive detection of single nematode via direct MALDI Mass
      Spectrometry.
AB  - For the first time, we demonstrate the feasibility for the use of MALDI-TOF MS
      for rapid, direct and sensitive detection of single adult root-knot nematode,
      Meloidogyne incognita and their second stage juvenile (J(2)). We have proposed
      simple pretreatment protocols and have demonstrated that the crushed and washed
      nematodes yielded better spectra. We also report the differentiation between the
      harmless and harmful stages of the nematode based on mass spectrometric
      profiling. Peaks at m/z 4350, 4692, 4933, 8725 were only present in the adult
      stages, while m/z 3220, 3433, 3485, 3830, 6540, 7444, 7770 were unique to the
      J(2) infective stage. The only common peak to both the phases was at m/z 3277.
      Thus, we show that MALDI-TOF MS can be used to differentiate between the
      infective and non-infective stage of the nematode and the detection sensitivity
      of MALDI-MS could be applied to a single nematode analysis.

PMID- 22483897
TI  - LabVIEW control software for scanning micro-beam X-ray fluorescence spectrometer.
AB  - Confocal micro-beam X-ray fluorescence microscope was constructed. The system was
      assembled from commercially available components - a low power X-ray tube source,
      polycapillary X-ray optics and silicon drift detector - controlled by an in-house
      developed LabVIEW software. A video camera coupled to optical microscope was
      utilized to display the area excited by X-ray beam. The camera image calibration
      and scan area definition software were also based entirely on LabVIEW code.
      Presently, the main area of application of the newly constructed spectrometer is
      2-dimensional mapping of element distribution in environmental, biological and
      geological samples with micrometer spatial resolution. The hardware and the
      developed software can already handle volumetric 3-D confocal scans. In this
      work, a front panel graphical user interface as well as communication protocols
      between hardware components were described. Two applications of the spectrometer,
      to homogeneity testing of titanium layers and to imaging of various types of
      grains in air particulate matter collected on membrane filters, were presented.

PMID- 22483898
TI  - Determination of quinolones of veterinary use in bee products by ultra-high
      performance liquid chromatography-tandem mass spectrometry using a QuEChERS
      extraction procedure.
AB  - A reliable and rapid ultra high performance liquid chromatography tandem mass
      spectrometry (UHPLC-MS/MS) method has been developed for the determination of the
      eight quinolones of veterinary use regulated by European Union (marbofloxacin,
      ciprofloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, flumequine
      and oxolinic acid). Chromatographic conditions were optimized in order to
      increase sample throughput and sensitivity. The antibiotics were detected by
      electrospray ionization in positive ion mode with multiple reaction monitoring
      (MRM) and MS/MS conditions were optimized in order to increase selectivity,
      selecting the corresponding product ions for quantification and identification.
      The separation was achieved in 3 min, using a Zorbax Eclipse Plus C18 column (50
      mm * 2.1mm, 1.8 MUm), with a mobile phase of 0.02% aqueous formic acid solution
      and acetonitrile. A dispersive solid phase extraction methodology, often referred
      to as the "QuEChERS" (quick, easy, cheap, effective, rugged, and safe) method,
      was optimized for extraction of the quinolones from honey and also it was
      evaluated for other bee products such as royal jelly and propolis. The method was
      validated for each matrix in terms of linearity, trueness, precision, limits of
      detection (LODs) and quantification (LOQ). LODs ranged between 0.2 and 4.1 MUg
      kg(-1) with precision lower than 12% and satisfactory recoveries in most cases.
      The method was also applied for studying the occurrence of these antibiotics in
      several market samples.

PMID- 22483899
TI  - The potential of ion mobility spectrometry (IMS) for detection of 2,4,6
      trichloroanisole (2,4,6-TCA) in wine.
AB  - The off-flavor of "tainted wine" is attributed mainly to the presence of 2,4,6
      trichloroanisole (2,4,6-TCA) in the wine. In the present study the atmospheric
      pressure gas-phase ion chemistry, pertaining to ion mobility spectrometry, of
      2,4,6-trichloroanisole was investigated. In positive ion mode the dominant
      species is a monomer ion with a lower intensity dimer species with reduced
      mobility values (K(0)) of 1.58 and 1.20 cm(2)V(-1) s(-1), respectively. In
      negative mode the ion with K(0) =1.64 cm(2)V(-1)s(-1) is ascribed to a
      trichlorophenoxide species while the ions with K(0) =1.48 and 1.13 cm(2)V(-1)s(
      1) are attributed to chloride attachment adducts of a TCA monomer and dimer,
      respectively. The limit of detection of the system for 2,4,6-TCA dissolved in
      dichloromethane deposited on a filter paper was 2.1 MUg and 1.7 ppm in the gas
      phase. In ethanol and in wine the limit of detection is higher implying that pre
      concentration and pre-separation are required before IMS can be used to monitor
      the level of TCA in wine.

PMID- 22483900
TI  - Identification, characterization and cytotoxicity in vitro assay of nitazoxanide
      major degradation product.
AB  - Stress studies of the broad-spectrum antiparasitic nitazoxanide were conducted in
      order to isolate and elucidate the major degradation product involved in thermal,
      acid, alkaline, oxidative and photolytic decomposition of the drug in solution
      and solid state. The major degradation product was identified and characterized
      using techniques namely LC-DAD, (1)H NMR, (13)C NMR, IR, and MS/MS. The stability
      of nitazoxanide raw material and nitazoxanide in tablets and in suspension powder
      was studied under different conditions and the results suggest the formation of
      the same deacetylated degradation product occur in all cases. This product was
      also studied in order to determine the preliminary cytotoxicity in vitro with
      mononuclear cells. Compared with nitazoxanide, the degradation product showed a
      higher cytotoxicity at a concentration of 40 MUg mL(-1) after 48 h of incubation,
      under tested conditions. Therefore, stress studies showed that special care must
      be taken during the preparation, manufacture, and storage of this pharmaceutical
      drug.

PMID- 22483901
TI  - Relation factor: a new strategy for quality control in the determination of
      pesticides in environmental aqueous matrices.
AB  - The effects promoted by environmental aqueous matrices on pesticide
      determinations have been assessed, and for the first time, a simple, low-cost and
      efficient strategy for the correction of analytical results has been determined.
      This method can be useful as a parameter of quality control in a quality
      assurance programs. Evaluation of the matrix effect showed that environmental
      aqueous matrices, e.g., estuarine water, promote a distinctive and significant
      effect on the determination of pesticides. The picloram, atrazine and methyl
      parathion pesticides suffered the smallest effects promoted by the estuarine
      matrix, whereas chlorpyrifos and cypermethrin suffer a significant effect. For
      picloram, the matrix effect was a function of its physiochemical properties.
      However, for atrazine, methyl parathion, chlorpyrifos and cypermethrin, the
      matrix effect was promoted by environmental matrix components. As strategy for
      analytical quality control, it has been determined that there are relation
      factors (RFs) between pesticides and the selected surrogates standards. These RFs
      are not altered by the complexities and compositions of simple and complex
      aqueous matrices. Predetermined RFs was applied to the picloram, atrazine and
      methyl parathion assessment in a real sample from the estuary of the Jaguaribe
      River, and the results showed that when no quality control was applied, the
      concentration levels would be underestimated, leading to incorrect results and
      inaccurate conclusions.

PMID- 22483902
TI  - Surface plasmon resonance shows a gender difference in circulating annexin A5 in
      human.
AB  - The level of circulating anxA5 is correlated to various diseases such as acute
      myocardial infarction, trauma, thrombosis, inflammation and in some cancers. Our
      aim was to assess whether a direct approach using surface plasmon resonance (SPR)
      could be easily used to provide a rapid and cheap alternative to detect anxA5 in
      blood samples in human. Our results indicate that SPR permits to detect and
      quantify circulating anxA5 in serum with a minimum time of manipulation.
      Furthermore, we report here, for the first time, that the level of circulating
      anxA5 is significantly higher in male than in female (5.43 (+/- 0.02) and 4.41
      (+/- 0.2)ng/ml, respectively). In conclusion, we found that SPR can be used to
      rapidly quantify anxA5 in patients and that a gender difference has to be taken
      into account to explain gender differences in the prevalence of some diseases.

PMID- 22483903
TI  - Determination of carboxylic acids in water by gas chromatography-mass
      spectrometry after continuous extraction and derivatisation.
AB  - This paper describes a new approach for the determination of monocarboxylic,
      dicarboxylic and tricarboxylic acids (35 compounds) in water. The analytes, in
      acid medium (pH ~ 1.3), were sorbed on an 80 mg LiChrolut EN-Supelclean ENVI-18
      (1:1) column and subsequently eluted with methanol. After evaporation of the
      extract to ~ 10 MUL, the analytes were spiked with 60 MUL of the derivatising
      reagent and derivatised in a household microwave oven for 3 min. Among the
      reagents tested (BF(3)/1-butanol; acetyl chloride/1-butanol; isobutyl
      chloroformate/1-butanol; trimethylphenylammonium hydroxide, N,O-bis
      (trimethylsilyl)acetamide, N,O-bis-(trimethylsilyl)trifluoroacetamide and
      trimethylchlorosilane), the best results in terms of reaction yield and stability
      of the derivatives were obtained with the mixture of 1% trimethylchlorosilane in
      N,O-bis-(trimethylsilyl)trifluoroacetamide. Microwave assisted derivatisation was
      used as an alternative heating approach for the rapid silylation of carboxylic
      acids. The proposed method proved to be a suitable analytical procedure for
      several types of carboxylic acids in water, with limits of detection within the
      range 0.6-15 ng L(-1), precision values from 4.0 to 6.0% (as within-day relative
      standard deviation) and recoveries from 93 to 101% for all the target analytes.

PMID- 22483904
TI  - The discrimination between phospholipids of diverse structure and
      phosphacoumarins of various hydrophobicity through fluorescent response of Tb
      doped silica nanoparticles decorated by cationic surfactant.
AB  - The work represents colloids of silica nanoparticles displaying fluorescent
      response on biorelevant compounds exemplified by phosphacoumarins and
      phospholipids. The luminescent properties of the colloids arise from Tb(III)
      complexes doped into silica nanoparticles (SNs). The noncovalent decoration of
      SNs by dicationic surfactant with further interfacial binding of dye anions
      enables to develop colloids programmed to display a substrate induced fluorescent
      response. The latter results from the quenching of Tb(III) centered luminescence
      by dye anions through dynamic mechanism and subsequent displacement of quenching
      anions by the non-quenching substrates from the interface of SNs. Both negative
      charge and hydrophobicity of substrates are the key factors affecting the
      selectivity of the substrate induced fluorescent response. The peculiar effects
      of zwitter-ionic and anionic phospholipids on the fluorescent response have been
      revealed. The applicability of the fluorescent procedure in the sensing of
      impurities in commercial phosphatidylcholine is also introduced.

PMID- 22483905
TI  - Characterization of interactions between organotin compounds and human serum
      albumin by capillary electrophoresis coupled with inductively coupled plasma mass
      spectrometry.
AB  - Thermodynamic data such as the binding constants are vital parameters describing
      interactions between exotic trace compounds and biomolecules in biochemical
      property modeling. In this study, the stability constants of organometallic
      compound and protein complexes were studied by using capillary electrophoresis
      coupled with inductively coupled plasma mass spectrometry (CE-ICP-MS),
      considering its low detection limits and low sample demand. Four organotin
      compounds (trimethyltin (TMT), tripropyltin (TPrT), tributyltin (TBT),
      triphenyltin (TPhT)) and human serum albumin (HSA) were used as model
      organometallic compounds and protein, respectively. Affinity capillary
      electrophoresis (ACE) and nonequilibrium capillary electrophoresis assays of
      equilibrium mixtures (NECEEM) were performed and compared by using ICP-MS as the
      detector to determine the binding constants of organotin compounds and HSA in 1:1
      molar ratio assumption. Constant measurements of the two methods were both
      simple, however, ACE assays were more accurate and more appropriate for the
      constant determination of the organotin-HSA complexes, considering the errors of
      the NECEEM method. A good precision of the binding constants (log K(b)) using the
      ACE method was proved by different mathematical calculations, and the values were
      6.13 +/- 0.51 (TMT), 5.72 +/- 0.38 (TPrT), 5.68 +/- 0.34 (TBT), 6.05 +/- 0.38
      (TPhT) respectively for each of the organotin-HSA complexes, showing non-covalent
      interaction between organotin compounds and HSA. Meanwhile, this study also
      confirms the suitability of CE-ICP-MS method for further studies on
      organometallic complexation.

PMID- 22483906
TI  - Solvent-based de-emulsification dispersive liquid-liquid microextraction of
      palladium in environmental samples and determination by electrothermal atomic
      absorption spectrometry.
AB  - A new simple, rapid and efficient sample pretreatment technique for simultaneous
      extraction and preconcentration was developed. In this study, solvent-based de
      emulsification dispersive liquid-liquid microextraction (SD-DLLME) was developed
      for preconcentration and highly sensitive determination of Pd(II) using the
      electrothermal atomic absorption spectrometry. The extraction of Pd(II) was
      performed in the presence of Thio-Michler's ketone (TMK) as the complexing agent.
      After dispersing, when an aliquot of acetonitrile was introduced as a chemical
      demulsifier into the aqueous bulk, the obtained emulsion cleared into two phases
      quickly. Therefore, an extra centrifugation step is not needed for phase
      separation. Several factors that influence the microextraction efficiency and
      ETAAS signal, such as pH, TMK concentration, counter ion, extraction time,
      disperser, de-emulsifier solvents and extraction solvents, stirring rate,
      pyrolysis and atomization temperature were investigated. Under the optimized
      conditions, the calibration graph was linear over the range of 0.025-0.500 MUg L(
      1) and relative standard deviation of 3.68% at 0.1 MUg L(-1) was obtained (n=7).
      The limit of detection and the enrichment factor (EF) were obtained 0.007 MUg L(
      1) and 231, respectively. The obtained results indicated that the developed
      method is an excellent alternative for the routine analysis in the environmental
      field.

PMID- 22483907
TI  - Gas-phase fragmentation of host-guest complexes between beta-cyclodextrin and
      small molecules.
AB  - Noncovalent interactions are ubiquitous in molecular interaction and
      supramolecular self-assembly. As a model system, host-guest complexes between
      beta-cyclodextrin (beta-CD) and small molecules have been extensively studied and
      widely used in a variety of application fields including drug transportation and
      fluorescence enhancement. However, details on how guest molecules interact with
      the beta-CD hosts to demonstrate the observed effects still remain to be further
      studied. In this work, we report the study of gas-phase fragmentation of host
      guest complexes formed between beta-CD and small guest molecules by using
      collision induced dissociation (CID). The CID mass spectra of the complexes
      changed dramatically as the collision energy was increased. Fragmentation
      patterns of beta-CD complexed with different small molecules were analyzed and
      the differences in the presence/absence of fragment ions from the beta-CD were
      attributed to varied proton affinity of the small molecules. Furthermore, the
      CE(50) values fitted from the fragmentation curves were used in the qualitative
      evaluation of interactions in noncovalent host-guest systems.

PMID- 22483908
TI  - Growth and properties of Ag-doped ZnO nanoflowers for highly sensitive phenyl
      hydrazine chemical sensor application.
AB  - We report here the fabrication of a robust, highly sensitive, reliable and
      reproducible phenyl hydrazine chemical sensor using Ag-doped ZnO nanoflowers as
      efficient electron mediators. The Ag-doped ZnO nanoflowers were synthesized by
      facile hydrothermal process at low-temperature and characterized in detail in
      terms of their morphological, structural, compositional and optical properties.
      The detailed morphological and structural characterizations revealed that the
      synthesized nanostructures were flower-shaped, grown in very high-density, and
      possessed well-crystalline structure. The chemical composition confirmed the
      presence of Ag into the lattices of Ag-doped ZnO nanoflowers. High sensitivity of
      ~ 557.108 +/- 0.012 mAcm(-2)(mol L(-1))(-1) and detection limit of ~ 5 * 10(-9)
      mol L(-1) with correlation coefficient (R) of 0.97712 and short response time
      (10.0 s) were observed for the fabricated chemical sensor towards the detection
      of phenyl hydrazine by using a simple current-voltage (I-V) technique. Due to
      high sensitivity and low-detection limit, it can be concluded that Ag-doped ZnO
      nanoflowers could be an effective candidate for the fabrication of phenyl
      hydrazine chemical sensors.

PMID- 22483909
TI  - Probing cysteine self-assembled monolayers over gold nanoparticles--towards
      selective electrochemical sensors.
AB  - Cysteine forms self-assembled monolayers over gold nanoparticles. Based on this
      knowledge, a novel electrochemical sensor (Au-Au(nano)-Cys-SDS) has been
      constructed by the formation of self-assembly monolayer (SAM) of cysteine on gold
      nanoparticles modified gold electrode (Au-Au(nano)-Cys) to be utilized for
      determination of dopamine in the presence of sodium dodecyl sulfate (SDS).
      Electrochemical investigation and characterization of the modified electrode
      sensor was achieved using cyclic voltammetry, electrochemical impedance
      spectroscopy, scanning electron, and atomic force microscopies. Au-Au(nano)-Cys
      electrode in the presence of SDS gave comparable high current response to that of
      the gold nanoparticles modified gold electrode (Au-Au(nano)). The Au-Au(nano)-Cys
      SDS electrode current signal was remarkably stable via repeated cycles and long
      term stability due to the strong AuS bond. Very small peak separation, almost
      zero or 15 mV peak separation was also obtained by repeated cycles indicating
      unusual high reversibility. The oxidation peak current was determined to be
      linearly dependent on the dopamine concentration. A resulting calibration curve
      using square wave voltammetry (SWV) was obtained over concentration range of 30
      100 MUmol L(-1) and 120-320 MUmol L(-1) with correlation coefficients of 0.996
      and 0.994 and a limit of detection of 16 and 57 nmol L(-1), respectively. Using
      differential pulse voltammetry (DPV), a highly selective and simultaneous
      determination of tertiary mixture of ascorbic acid AA, dopamine, and
      acetaminophen APAP was explored at this modified electrode. It has been
      demonstrated that Au-Au(nano)-Cys-SDS electrode can be used as a sensor with
      excellent reproducibility, sensitivity, and long term stability.

PMID- 22483910
TI  - Boron nitride nanotubes and their functionalization via quinuclidine-3-thiol with
      gold nanoparticles for the development and enhancement of the HPLC performance of
      HPLC monolithic columns.
AB  - In this paper, a new and effective method was described for attaching gold
      nanoparticles (Au-NPs) on to the surface of thiol-terminated Boron Nitride
      Nanotubes (BNNT) functionalized with quinuclidine-3-thiol, acting as a bridging
      agent. The quinuclidine-3-thiol was first grafted onto the surface of the BNNTs
      via strong interactions between the electron pair from the nitrogen atom of the
      quinuclidine structure and the electronic gap from the boron atom of the BNNT.
      The bare surface of Au-NPs facilitates to attach on the thiol group of the thiol
      terminated BNNTs. These two nanomaterials (pristine BNNTs and Au-BNNTs) were then
      incorporated into a monolithic polymer. The obtained monolithic BNNT and AuBNNT
      stationary phases were very useful columns for the HPLC isocratic mode separation
      of a series of benzene and naphtalene derivatives. The retention on these two
      stationary phases was due to the different intermolecular interactions including
      the dispersion interaction (area of the delocalized pi bond), the dipole-dipole
      interactions, and the electrostatic repulsion. The presence of Au-NPs on the BNNT
      surface improved significantly the retention and column efficiency for compounds
      with thiol groups in their structure. As well, it was shown that both retention
      and column efficiency linearly increased with the nanotube (NT) amount in the
      polymerization mixture. This manuscript thus established for the first time the
      fact that BNNT was a very useful nanomaterial for the development of novel HPLC
      stationary phases and increased the performance of classical equivalent C18
      monolithic columns.

PMID- 22483911
TI  - A simple approach for retention prediction in the pH-gradient reversed-phase
      liquid chromatography.
AB  - A simple approach for retention modeling of solutes under pH-gradient conditions
      at various organic contents in the mobile phase is proposed. This approach is
      based on a retention model arising from the evaluation of the retention data of a
      set of 17 OPA derivatives of amino acids obtained in two series of 22 pH-gradient
      runs performed between a given initial and final pH value (between 2.8 and 10.7
      or 3.2 and 9.0) with different gradient duration and with different organic
      modifier content in the eluent. The derived model is a fifth-parameter equation
      easily manageable through a linear least-squares fitting. It requires only 6
      initial pH-gradient experiments, allows a very satisfactory prediction for
      various pH-changes of the same kind with those used in the fitting procedure and
      seems to be very promising in separation optimization under pH-gradient
      conditions. The pH-gradient method appears to be especially suitable and
      effective for separation of amino acid derivatives whereas the application of pH
      gradients from 3.2 to 9.0 proved to be beneficial.

PMID- 22483912
TI  - Potentiometric electronic tongue-flow injection analysis system for the
      monitoring of heavy metal biosorption processes.
AB  - An automated flow injection potentiometric (FIP) system with electronic tongue
      detection (ET) is used for the monitoring of biosorption processes of heavy
      metals on vegetable wastes. Grape stalk wastes are used as biosorbent to remove
      Cu(2+) ions in a fixed-bed column configuration. The ET is formed by a 5-sensor
      array with Cu(2+) and Ca(2+)-selective electrodes and electrodes with generic
      response to heavy-metals, plus an artificial neural network response model of the
      sensor's cross-response. The real-time monitoring of both the Cu(2+) and the
      cation exchanged and released (Ca(2+)) in the effluent solution is performed by
      using flow-injection potentiometric electronic tongue system. The coupling of the
      electronic tongue with automation features of the flow-injection system allows us
      to accurately characterize the Cu(2+) ion-biosorption process, through obtaining
      its breakthrough curves, and the profile of the Ca(2+) ion release. In parallel,
      fractions of the extract solution are analysed by spectroscopic techniques in
      order to validate the results obtained with the reported methodology. The
      sorption performance of grape stalks is also evaluated by means of well
      established sorption models.

PMID- 22483913
TI  - Improved liquid-chromatography tandem mass spectrometry method for the
      determination of the bioactive dipeptides, carnosine and anserine: application to
      analysis in chicken broth.
AB  - An improved method, based on ultra-performance liquid chromatography (UPLC)
      coupled to tandem mass spectrometry (MS/MS), has been developed to determine the
      bioactive dipeptides carnosine (CAR) and anserine (ANS) in chicken broth. These
      analytes are hydrophilic (polar) and in order to improve their retention, the
      chromatographic mode used was hydrophilic interaction chromatography (HILIC) (1.7
      MUm particle size). In order to remove the salt before the chromatographic
      analysis of the chicken broth (0.8%, w/w), an exhaustive sample pre-treatment
      strategy was necessary since the salt is not volatilized and could block the
      ionization source and lead to signal suppression. The chicken broth was firstly
      centrifuged to remove the fat and chicken proteins, and then was pretreated by
      off-line solid-phase extraction (SPE), using traditional cartridges, or off-line
      MUElution plate (MUSPE), using microplates, and the results were compared. Due to
      the high polar character of the dipeptides studied and the sample matrix, these
      compounds were not retained in the sorbent hydrophilic-lipophilic balanced (HLB)
      and were eluted in the load step, whereas the salt was retained in the sorbent.
      This fact was observed by the addition of silver nitrate in the chicken broth
      extract, where before the SPE or MUSPE a white precipitate (silver chloride) was
      formed and after the SPE or MUSPE this precipitate was not observed. By using
      these sample pre-treatment strategies, the extraction recoveries were higher than
      80%, and the matrix effect was lower than 12%. Once the improved method was
      developed, the quality parameters of the method were studied. The LODs and LOQs
      of the CAR and ANS were lower than 6 and 1.8 MUg/l, respectively. Then, the
      method was applied to analyse a commercial chicken broth. This improved method
      allowed determining CAR and ANS between 6 and 10mg dipeptide/l chicken broth in
      10 min (sample pre-treatment and chromatographic analysis). Therefore, the
      proposed improved method is concluded to be rapid, sensitive and selective for
      the determination of polar compounds by MS in samples that contain salt.

PMID- 22483914
TI  - Development of acid phosphatase based amperometric biosensors for the inhibitive
      determination of As(V).
AB  - An enzymatic amperometric procedure for the direct measurement of As(V) in the
      presence of As(III) was developed. The method is based on the inhibitive action
      of this species on acid phosphatase enzyme (AcP) activity. Screen-printed carbon
      electrodes (SPCEs) were used as support for the cross-linking immobilization of
      the enzyme AcP. 2-Phospho-l-ascorbic acid was used as a novel substrate, in
      arsenic determination, which amperometric response decreased by the presence of
      As(V) ions. The optimum working conditions were found using experimental design
      methodology. Under these conditions, repeatability and reproducibility of the
      constructed biosensors were determined, reaching values below 8% in terms of
      residual standard deviation. The capability of detection obtained for As(V) was
      0.11 MUM for AcP/SPCE biosensors. Analysis of the possible effect of the presence
      of foreign ions in the solution was performed. The method was successfully
      applied to the determination of the As(V) content in a ground water sample.

PMID- 22483915
TI  - Isotope dilution direct injection mass spectrometry method for determination of
      four tyrosine kinase inhibitors in human plasma.
AB  - BACKGROUND: Therapeutic drug monitoring is recommended for the optimal management
      of patients with several malignant diseases. The aim of this study was to develop
      and validate an isotope dilution direct injection mass spectrometry method for
      the high throughput determination of tyrosine kinase inhibitors in plasma from
      leukemic and cancer patients. METHODS: The plasma for analysis was deproteinated
      by methanol and the centrifuged supernatant was directly injected to mass
      spectrometer without separation step. Multiple reaction monitoring modes on a
      hybrid triple quadrupole - linear ion trap mass spectrometer (5500 QTRAP) were
      used for the detection and quantification of imatinib, nilotinib, lapatinib, and
      dasatinib. RESULTS: We developed a fast method with analysis time of 55 s and 19s
      in multiple injection setting. The method was successfully validated and applied
      to the patient plasma samples. In order to overcome insufficient sensitivity of
      dasatinib, multiple reaction monitoring cube mode in linear ion trap (MRM(3)) was
      successfully applied. The limits of quantification were in the range 1.0-5.5
      ng/ml. Imprecisions were lower than 6.9% and the accuracy of the quality control
      samples ranged between 99.0 and 107.9%. CONCLUSIONS: Isotope dilution direct
      injection mass spectrometry method allows high-throughput therapeutic drug
      monitoring of tyrosine kinase inhibitors in plasma. The method offers low-cost
      analyses as a result of its speed and the exclusion of separation step and can be
      advantageously used in routine clinical practice. The method can be applied on
      various drugs and biochemical markers with the use of triple quadrupole
      instruments.

PMID- 22483916
TI  - A co-immobilized mediator and microorganism mediated method combined pretreatment
      by TiO2 nanotubes used for BOD measurement.
AB  - In this paper, we proposed a method by using co-immobilized Escherichia coli (E.
      coli) as a biocatalyst and neutral red (NR) as an artificial electronic acceptor
      to modify glassy carbon electrode (GCE) for biochemical oxygen demand (BOD)
      measurement. Two different modification approaches of GCE were utilized and
      compared. In one approach, NR was electropolymerized on the surface of GCE, and
      E. coli cells were mixed with grafting copolymer PVA-g-PVP (briefly gPVP) and
      covered on NR polymer film to obtain a (gPVP/E. coli)/PNR/GCE. In the second
      approach, both NR and E. coli cells were mixed with the copolymer gPVP and
      modified GCE, after drying, which was electrochemically treated similar as above
      for obtaining a (gPVP/E. coli/NR)p/GCE. Based on the electrochemical evaluation,
      the performance of the latter was better, which may be caused by that the NR
      deposited on the surface of E. coli resulting in a good electron transport and
      permeability of cells membrane. To develop the results obtained at (gPVP/E.
      coli/NR)p/GCE further, the pretreatment by TiO(2) nanotubes arrays (TNTs) was
      employed, and different effects on samples of GGA, OECD, urea and real wastewater
      were evaluated. These results suggest that the present method holds a potential
      application for rapid BOD biosensor.

PMID- 22483917
TI  - Simultaneous electrochemical determination of uric acid, xanthine and
      hypoxanthine based on poly(L-arginine)/graphene composite film modified
      electrode.
AB  - Poly(l-arginine)/graphene composite film modified electrode was successfully
      prepared via a facile one-step electrochemical method and used for simultaneous
      determination of uric acid (UA), xanthine (XA) and hypoxanthine (HX). The
      electrochemical behaviors of UA, XA and HX at the modified electrode were studied
      by cyclic voltammetry and differential pulse voltammetry (DPV), and showed that
      the modified electrode exhibited excellent electrocatalytic activity toward the
      oxidation of the three compounds. The calibration curves for UA, XA and HX were
      obtained over the range of 0.10-10.0, 0.10-10.0 and 0.20-20.0 MUM by DPV,
      respectively and the detection limits for UA, XA and HX were 0.05, 0.05 and 0.10
      MUM (S/N=3), respectively. With good selectivity and high sensitivity, the
      modified electrode has been applied to simultaneous determination of UA, XA and
      HX in human urine with satisfactory result.

PMID- 22483918
TI  - Thallium speciation in plant tissues-Tl(III) found in Sinapis alba L. grown in
      soil polluted with tailing sediment containing thallium minerals.
AB  - Besides the dominant species in plants-Tl(I), noticeable amounts of Tl(III)
      (about 10% of total Tl content) were found in extracts of plants cultivated in
      the presence of tailing sediments, which are the main source of anthropogenic
      thallium already present in the environment. It is an important step of gaining
      knowledge about the detoxification mechanisms developed by Sinapis alba. This
      plant species is highly tolerant to Tl and it is able to cumulate high amounts of
      Tl and transport it into the above-ground organs. For more adequate estimation of
      accumulating abilities of S. alba, the elements' bioavailability was taken into
      consideration. The obtained bioconcentration factors of Cd (AF=0.6) and Zn (AF=1
      2) were significantly lower than of Tl (AF=100-200). The biomass production was
      similar to the biomass of control cultivation. The results were based on ICP MS
      measurements of total elements' content and HPLC ICP MS for speciation analysis.
      The quality of obtained results was evaluated based on the intermethod comparison
      with voltammetry as a reference method. Comparison of data obtained using ICP MS
      and electrochemical methods (after a proper chemical treatment) was also used for
      indication of Tl(III) presence and for proving that Tl(I) was not transferred
      into Tl(III) during analytical procedures.

PMID- 22483919
TI  - Highly selective and sensitive method for cysteine detection based on
      fluorescence resonance energy transfer between FAM-tagged ssDNA and graphene
      oxide.
AB  - In this work, a new platform for effective sensing cysteine (Cys) was developed
      based on fluorescence resonance energy transfer (FRET) between FAM-tagged single
      stranded DNA (FAM-ssDNA) and graphene oxide (GO). Due to the noncovalent assembly
      between FAM-ssDNA and GO, fluorescence quenching of the FAM took place because of
      FRET. This method relied on the competitive ligation of Ag(+) by Cys and
      "cytosine-cytosine" (C-C) mismatches in a FAM-labeled DNA strand of the self
      hybridizing strand. At first, enough amount of Ag(+) was introduced to bind "C-C"
      mismatches and form double-stranded DNA (dsDNA), which had weak affinity to GO
      and kept FAM away from GO surface. However, the presence of Cys removed Ag(+)
      away from "cytosine-Ag(+)-cytosine" (C-Ag(+)-C) base pairs, leading to the
      formation of ssDNA again and FRET, and then fluorescence of the FAM-ssDNA was
      efficiently quenched. The fluorescence intensity decrease was found to be
      proportional to the increase of concentration of Cys in both aqueous buffer (2
      200 nM) and human serum (5-200 nM), and the sensitivity of the proposed method
      towards Cys was much higher than that of other reported assays for Cys.

PMID- 22483920
TI  - Multiresidue analysis of aromatic organochlorines in soil by gas chromatography
      mass spectrometry and QuEChERS extraction based on water/dichloromethane
      partitioning. Comparison with accelerated solvent extraction.
AB  - A novel multiresidue method was developed for the simultaneous analysis of 34
      organochlorines, including chlorobenzenes, chlorophenols, chlorinated
      hydrocarbons and chlorinated olefins, in soil by GC-MS, using a QuEChERS-based
      extraction. The conventional QuEChERS method was optimised and, for the first
      time, the use of a non miscible-water solvent was required. The method was
      compared to ASE extraction, versatile technique widely used for the soils'
      extraction and QuEChERS-based method was shown to be the most efficient in terms
      of recoveries, simplicity and rapidity. For ASE, recoveries between 42% and 85%
      were obtained for the majority of the compounds. However, due to the high
      pressure, all volatile compounds were lost. In opposite, QuEChERS extraction
      allowed detection and quantification of all the compounds with recoveries between
      60% and 100%. Moreover, no additional clean up by dispersive SPE on PSA was
      necessary, which allowed reducing the cost of the analysis. Performance of the
      method was assessed. The method was linear over the range of concentration of 10
      5000 MUg kg(-1). Precision, expressed as intra-day precision and inter-day
      variation was verified at three concentrations. Limits of detection were from 2
      to 50 MUg kg(-1) and limits of quantification from 7 to 170 MUg kg(-1) for the
      majority of the compounds (chlorobenzenes and chlorinated hydrocarbons and
      olefins), except for chlorophenols. The method was further applied to different
      soils coming from a contaminated industrial site, where a new environmental
      remediation process, using phytoremediation, was tested. The results showed that
      the method could be applied to any kind of soils (mineral or organic) and was
      appropriate to very volatile compounds which were not available with conventional
      technique.

PMID- 22483921
TI  - One-step synthesis of graphene-AuNPs by HMTA and the electrocatalytical
      application for O2 and H2O2.
AB  - A green, one-step method for synthesis of graphene-Au nanoparticles (graphene
      AuNPs) was introduced in this article, using an environmentally benign
      hexamethylenetetramine (HMTA) as reducing and stabilizing agent. HMTA slowly was
      hydrolyzed to generate aldehyde ammonia to reduce graphene oxides (GO) and
      hydrogen tetrachloroaurate (Au precursor). The structure and composition of the
      graphene-AuNPs nanocomposites were studied by means of ultraviolet visible (UV)
      absorption spectra, X-ray photoelectron spectroscopy (XPS) and Transmission
      electron microscopy (TEM). The AuNPs are well-dispersed on graphene nanosheets in
      narrow size range. The nanocomposites have excellent electrocatalytical
      properties for catalytic reduction of O(2) and H(2)O(2).

PMID- 22483922
TI  - Preparation and characterization of chitosan/graphene oxide composites for the
      adsorption of Au(III) and Pd(II).
AB  - In this work, graphene oxide (GO) was firstly prepared, following by element
      analysis. Glutaraldehyde cross-linked chitosan (GCCS) and chitosan/graphene oxide
      (CSGO) composite with three different amounts of GO (5 wt%, 10 wt% and 15 wt%)
      were also prepared for the adsorption of Au(III) and Pd(II) in aqueous solution.
      The properties of the adsorbents were investigated by Fourier transform infrared
      spectroscopy (FT-IR), X-ray diffraction (XRD) and surface area analysis. Batch
      adsorption studies were carried out. The adsorption of Au(III) and Pd(II) onto
      CSGO composites was optimum at pH 3.0-5.0 for Au(III) and pH 3.0-4.0 for Pd(II),
      which was much wider than that of GCCS. The adsorption isotherms obeyed the
      Langmuir isotherm models for the adsorption of Au(III) and Pd(II). Chitosan with
      5 wt% graphene oxide (CSGO(5)) composite had the largest adsorption capacity for
      Au(III) and Pd(II) compared with the other prepared adsorbents, where the maximum
      adsorption capacity were 1076.649 mg/g for Au(III) and 216.920 mg/g for Pd(II),
      respectively. The adsorption kinetics of Au(III) and Pd(II) onto CSGO(5) followed
      a pseudo-second-order kinetic model, indicating that the chemical adsorption was
      the rate-limiting step. Thermodynamic parameters, such as Gibbs energy (DeltaG
      degrees ), enthalpy (DeltaH degrees ), and entropy (DeltaS degrees ), were
      calculated, showing that the adsorption of Au(III) and Pd(II) onto CSGO(5) were
      spontaneous, endothermic and feasible. The desorption studies of Au(III) and
      Pd(II) onto CSGO(5) showed that CSGO(5) can be used repeatedly without
      significantly changing its adsorption capacity and desorption percentage after 3
      cycles. Besides CSGO(5) was successfully applied for the determination and
      separation of Au(III) and Pd(II) in ore samples.

PMID- 22483923
TI  - Peptide-based electrochemical biosensor for amyloid beta 1-42 soluble oligomer
      assay.
AB  - Based on oligopeptide, a novel strategy to fabricate electrochemical biosensor is
      proposed in this work by fine-tuning the scan pulse frequency of square wave
      voltammetry (SWV) to synchronize with the surface electron transfer (ET) of the
      oligopeptide modified on an electrode surface. By using this strategy, the
      surface ET dynamics of our peptide-based biosensor can show significant
      difference in the presence and absence of a detection target, thus the proposed
      strategy has been employed for the assay of amyloid beta 1-42 (Abeta 1-42)
      soluble oligomer, which is among the most neurotoxic species of Abeta peptide.
      Experimental results reveal that our sensor might be an appropriate candidate for
      quantitative assay of Abeta 1-42 soluble oligomer. Moreover, the strategy
      proposed in this work may be extended for the fabrication of more peptide-based
      biosensors in the future.

PMID- 22483924
TI  - Gold-silver-nanoclusters having cholic acid imprinted nanoshell.
AB  - Molecular imprinted polymers (MIPs) as a recognition element for sensors are
      increasingly of interest and MIP-nanoparticles have started to appear in the
      literature. In this study, we have proposed a novel thiol ligand-capping method
      with polymerizable methacryloylamido-cysteine (MAC) attached to gold-silver
      nanoclusters reminiscent of a self-assembled monolayer and have reconstructed
      surface shell by synthetic host polymers based on molecular imprinting method for
      cholic acid recognition. In this method, methacryloylamidohistidine-Pt(II) [MAH
      Pt(II)] has used as a new metal-chelating monomer via metal coordination
      chelation interactions and cholic acid. Nanoshell sensors with templates give a
      cavity that is selective for cholic acid. The cholic acid can simultaneously
      chelate to Pt(II) metal ion and fit into the shape-selective cavity. Thus, the
      interaction between Pt(II) ion and free coordination spheres has an effect on the
      binding ability of the gold-silver-nanoclusters nanosensor. The binding affinity
      of the cholic acid imprinted nanoparticles have investigated by using the
      Langmuir and Scatchard methods and determined affinity constant (K(affinity)) has
      found to be 2.73 * 10(4) mol L(-1) and 2.13 * 10(8) mol L(-1), respectively. At
      the last step of this procedure, cholic acid level in blood serum and urine which
      belong to a healthy people were determined by the prepared gold-silver
      nanoclusters.

PMID- 22483925
TI  - FTIR microspectroscopy discriminates anticancer action on human leukemic cells by
      extracts of Pinus kesiya; Cratoxylum formosum ssp. pruniflorum and melphalan.
AB  - Apoptosis is the principal molecular goal of chemotherapeutics for effective
      anticancer action. We studied the effect of 50% ethanolic-water extracts of Pinus
      kesiya, Cratoxylum formosum ssp. pruniflorum and melphalan on cytotoxicity and
      apoptosis induction for human leukemic U937 cells, and explored the mode of
      action using FTIR microspectroscopy. The number of viable U937 cells in vitro was
      decreased in a concentration-dependent manner by all tested compounds, although
      potency differed between the U937 and Vero cells. Melphalan and the extract of C.
      formosum exhibited relatively lower IC(50) values (15.0 +/- 1.0 and 82.7 +/- 3.2
      MUg/mL respectively) and higher selectivity (selective index>3) than the extract
      of P. kesiya (299.0 +/- 5.2 MUg/mL; selective index<3) on the U937 cells. All
      three compounds significantly induced apoptosis through the late stage - seen by
      the indicative DNA ladder - with the most effective being melphalan, then the P.
      kesiya and C. formosum extracts. FTIR microspectroscopy revealed that all three
      compounds raised the intensity of the beta-pleated sheet - higher than that of
      the untreated U937 cells - corresponding to a shift in the alpha-helix band
      associated with an alteration in the secondary structure of the protein band,
      confirming induction of apoptosis via pro-apoptotic proteins. The differences in
      intensity of the FTIR bands associated with lipids, proteins and nucleic acids
      were responsible for discrimination of the anticancer mode of action of each of
      the three compounds. The FTIR data suggest that the two plant extracts possessed
      anticancer activity with a different mode of action than melphalan.

PMID- 22483926
TI  - Determination of ten monohydroxylated polycyclic aromatic hydrocarbons by liquid
      liquid extraction and liquid chromatography/tandem mass spectrometry.
AB  - The aim of this study is to develop and validate an analytical method for the
      quantitation of ten urinary monohydroxylated polycyclic aromatic hydrocarbons (OH
      PAHs) through high pressure liquid chromatography/tandem mass spectrometry
      (HPLC/MS/MS). After enzymatic deconjugation, urine samples were extracted by
      liquid-liquid extraction (LLE) and OH-PAHs were analyzed by HPLC/MS/MS operated
      in negative electrospray ionization (ESI) and multiple reaction monitoring (MRM)
      mode. LLE was conducted with the solvent mixture of pentane and toluene, which
      reduced the matrix interferences and enhanced the method sensitivity
      significantly. Deuterated and (13)C-labeled analogs are used as internal
      standards. Calibration curves of all target analytes shows favorable linearity
      within the concentration range of 5.9-15,000.0 ng/L for different OH-PAHs with
      the regression coefficients above 0.993. The limits of detection (LODs) in pooled
      urine ranged from 1.72 to 17.47 ng/L, which were much lower than those obtained
      by a gas chromatography/high resolution mass spectrometry (GC/HRMS) method. The
      method shows satisfactory accuracy and precision when analyzing three different
      levels of OH-PAHs spiked in pooled urine. Except for 1-hydroxynaphthalene,
      recoveries of other OH-PAHs were in the range of 100 +/- 20% with a variation
      coefficient of less than 13%. The measurement of OH-PAHs from a QC sample of the
      Centers for Disease Control and Prevention (CDC) generated results close to the
      values measured by CDC. This method has been successfully employed in the
      California Biomonitoring Program.

PMID- 22483927
TI  - Determination of quartz in bulk materials from workplace environments using X-ray
      diffractometry and the absorption diffraction method.
AB  - A method is described for the determination of crystalline quartz in bulk
      materials from workplace environments as part of occupational hygiene
      investigations using X-ray powder diffractometry. The absorption-diffraction
      model was used for quantification with mass absorption coefficients for samples
      being experimentally determined using an absorption cell placed in front of the
      diffracted beam anti-scatter slit. The method was found to be reliable for
      samples containing from 0.5 to 100 wt.% crystalline quartz, where mass absorption
      coefficients did not exceed 120 cm(2)g(-1). Repeatability studies found that mass
      absorption coefficient determinations and crystalline quartz determinations were
      both generally within 1-2% relative standard deviation. The method was assessed
      for accuracy and found to be within 2% absolute when a National Institute of
      Standards and Technology (NIST) quartz certified reference material (SRM1879a)
      was analysed. The technique was compared to an internal standard procedure and a
      paired students t test showed that there was no significant statistical
      difference between the two methods at the 95% confidence level where the t value
      was found to be 0.40 (p>0.05=0.69) and the t critical value being
      t(crit,0.05,29)=2.05. The method was suitable for a variety of matrixes including
      those containing amorphous material and could be routinely applied to most
      samples of occupational interest.

PMID- 22483928
TI  - Enhanced fluorescence sensing of melamine based on thioglycolic acid-capped CdS
      quantum dots.
AB  - A sensitive and simple method for the determination of melamine (MA) was
      developed based on the fluorescence enhancement effect of MA for thioglycolic
      acid-capped (TGA-capped) CdS quantum dots (QDs). Under optimum conditions, a good
      linear relationship was obtained from 2.0 * 10(-9) to 5.0 * 10(-5)M. The
      detection limit was 1.0 * 10(-9)M, which was much lower than the safety limit
      (2.5 ppm in USA and the UK; 1 ppm for infant formula in China). The solution pH,
      the adding sequence of the buffer solution and MA and surface modifiers of CdS
      QDs greatly influenced the enhancement extent of MA for CdS QDs. The fluorescence
      enhancement was attributed to the surface passivation of the surface states of
      QDs by amine group of MA. The method was applied to detect MA in raw milk with
      satisfactory results. The proposed method manifested several advantages such as
      high sensitivity, short analysis time, low cost and ease of operation.

PMID- 22483929
TI  - Determination of mercury in fish otoliths by cold vapor generation inductively
      coupled plasma mass spectrometry (CVG-ICP-MS).
AB  - A method based on cold vapor generation inductively coupled plasma mass
      spectrometry (CVG-ICP-MS) has been developed for determination of inorganic
      mercury, Hg(II), and total mercury in fish otoliths. Sodium borohydride (NaBH(4))
      was used as the only reducing agent and its concentration was optimized across an
      acidity gradient to selectively reduce Hg(II) without affecting methylmercury,
      CH(3)Hg(I). Inorganic Hg was quantitatively reduced to elemental mercury (Hg(0))
      with 1 * 10(-4)% (m/v) NaBH(4). CH(3)Hg(I) required a minimum of 0.5% (m/v)
      NaBH(4) for complete reduction. Increasing the HCl concentration of solution to
      5% (v/v) improved the selectivity toward Hg(II) as it decreased the signals from
      CH(3)Hg(I) to baseline levels. Potassium ferricyanide solution was the most
      effective in eliminating the memory effects of Hg compared with a number of
      chelating and oxidizing agents, including EDTA, gold chloride, thiourea, cerium
      ammonium nitrate and 2-mercaptoethylamine chloride. The relative standard
      deviation (RSD) was less than 5% for 1.0 MUg L(-1) Hg(II) solution. The detection
      limits were 4.2 and 6.4 ng L(-1) (ppt) for Hg(II) and total Hg, respectively.
      Sample dissolution conditions and recoveries were examined with ultra-pure
      CaCO(3) (99.99%) spiked with Hg(II) and CH(3)HgCl. Methylmercury was stable when
      dissolution was performed with up to 20% (v/v) HCl at 100 degrees C. Recoveries
      from spiked solutions were higher than 95% for both Hg(II) and CH(3)Hg(I). The
      method was applied to the determination of Hg(II) and total Hg concentrations in
      the otoliths of red emperor (CRM 22) and Pacific halibut. Total Hg concentration
      in the otoliths was 0.038 +/- 0.004 MUg g(-1) for the red emperor and 0.021 +/-
      0.003 MUg g(-1) for the Pacific halibut. Inorganic Hg accounted for about 25% of
      total Hg indicating that Hg in the otoliths was predominantly organic mercury
      (e.g., methylmercury). However, as opposed to the bioaccumulation in tissues,
      methylmercury levels in otoliths was very low suggesting a different route of
      uptake, most likely through the deposition of methylmercury available in the
      water.

PMID- 22483930
TI  - CdSe and ZnSe quantum dots capped with PEA for screening C-reactive protein in
      human serum.
AB  - A fluorescence chemical sensor for C-reactive protein (CRP) was developed based
      on the selective interaction with CdSe and ZnSe quantum dots (QDs) coated with O
      phosphorylethanolamine (PEA). Synthesis procedure and analytical parameters such
      as pH and ionic strength were studied. The decrease in the fluorescence emission
      intensity was explained due to the specific interaction of the QDs-PEA with CRP,
      and a correlation was observed between the quenching of the fluorescence and the
      concentration of CRP. The accuracy of the proposed method was 0.37% as RSD. The
      proposed method was applied to screen serum samples, and showed to be sensible at
      the C-reactive protein concentrations of risks levels.

PMID- 22483931
TI  - A single procedure for the accurate and precise quantification of the rare earth
      elements, Sc, Y, Th and Pb in dust and peat for provenance tracing in climate and
      environmental studies.
AB  - The geochemical provenancing of atmospheric dust deposited in terrestrial
      archives such as peat bogs using trace elements is central to the study of
      atmospheric deposition over the continents and at the heart of many climate and
      environmental studies. The use of a single digestion method on all sample types
      involved in such a study (dust archive and sources) minimizes the contribution of
      the total analytical error when comparing sample compositions and attributing a
      source to the deposited dust. To date, this factor is limiting progress in
      geographical areas where the compositional variations between the sources and
      within the archive are small. Here, seven microwave and hot plate digestion
      methods were tested on rock, soil and plant reference materials to establish a
      unique method optimizing precision and accuracy in all sample types. The best
      results were obtained with a hot plate closed-vessel digestion with 2 ml HF and
      0.5 ml HNO(3) for 0.1g of sample, which allowed the precise, accurate and low
      blank quantification of the trace elements La-Yb, Sc, Y, Th and Pb by ICP-MS.
      This method was tested in a climate study in central Asia and temporal changes in
      the dominant dust source were for the first time successfully linked to changes
      in atmospheric circulation patterns above this region.

PMID- 22483932
TI  - All-solid-state selective electrodes using carbon black.
AB  - This study developed new types of all-solid-state ion-selective electrodes based
      on carbon black (CB). The electrodes were obtained basing on two methods. The
      first method concerned the addition of the CB as an intermediate layer between an
      ionophore-doped solvent polymeric membrane and an electrical conductor. The
      second one used the CB as a polymeric membrane component. The stability of the
      electrical potential of the new solid-contact electrodes was examined by
      performing the current-reversal chronopotentiometry and the influence of the
      interfacial water film was assessed by the potentiometric aqueous-layer test. The
      performance of the new electrodes was evaluated by the determining K(+) with an
      ion-selective membrane that contained the well known valinomycin ion carrier. The
      new electrodes had a Nernstian slope, a high stability, the reproducibility of
      the standard potential values and a very small potential drift.

PMID- 22483933
TI  - Development of a compact chemiluminescence system coupled with capillary
      electrophoresis for carbohydrate analysis.
AB  - As a kinetic process, chemiluminescence (CL) met great challenges while it was
      used in the detection methods coupled with capillary electrophoresis (CE). In
      this investigation, a newly recorded ultra-fast CL reaction of luminol-KIO(4)
      K(3)Fe(CN)(6) was observed to be completed in 0.65 s. It was adopted in a simple
      CE-CL system efficiently to avoid the peak-tailing and overlapping. With this
      compact system, an indirect determination of rhamnose, d-fructose, sucrose and
      beta-cyclodextrin was realized based on the corresponding negative CL peaks.
      These peaks were due to the displacement of luminol anions by the analyzed
      saccharide molecules in alkaline separation electrolyte. In this way, these four
      saccharides could be separated and determined in 16 min with adequate
      sensitivities and stabilities. No derivatization or pretreatment was required for
      the analysis, and it presents an attractive opportunity for routine tests of mono
      , di- and oligo-saccharides in a compact CE-CL system, even as a microchip
      device.

PMID- 22483934
TI  - Electrochemical immunosensor for competitive detection of neuron specific enolase
      using functional carbon nanotubes and gold nanoprobe.
AB  - An electrochemical immunosensor for detection of neuron specific enolase (NSE)
      was designed by immobilizing NSE covalently functionalized single-walled carbon
      nanotubes (NSE-SWNTs) on a glassy carbon electrode. The NSE-SWNTs not only
      enhanced electrochemical signal but also presented abundant antigen domains for
      competitive immunological recognition to anti-NSE primary antibody and then gold
      nanoprobes labeled with alkaline phosphatase conjugated secondary antibody (AP
      anti-IgG/AuNPs). The AP-anti-IgG/AuNPs exhibited highly catalytic activity toward
      enzyme substrate and significantly amplified the amperometric signal for target
      molecule detection. Based on the dual signal amplification of SWNTs and gold
      nanoprobe, the immunosensor could response down to 0.033 ng mL(-1) NSE with a
      linear range from 0.1 ng mL(-1) to 2 MUg mL(-1), and showed acceptable precision
      and reproducibility. The designed immunosensor was amenable to direct
      quantification of target protein with a wide range of concentration in complex
      clinical serum specimens. The assay results were in a good agreement with the
      reference values. The proposed electrochemical immunosensor provided a pragmatic
      platform for convenient detection of tumor markers in clinical diagnosis.

PMID- 22483935
TI  - Comparison of event-related potentials elicited by cardinal and oblique
      orientations with broad-band noise stimuli.
AB  - The experiments described here used event-related potentials (ERPs) to
      investigate the neural processes of the horizontal effect, in which visual
      performance is worst for horizontal and best for oblique orientations. EEGs were
      recorded while human adult subjects performed an orientation identification task
      with broad-band noise stimuli. The results showed that the difference between
      cardinal orientations and oblique orientations first occurred at P2 component
      around 200 ms post-stimulus onset, which is much later than the traditional
      oblique effect. Additionally, the P3 was much smaller and earlier for oblique
      orientations than for cardinal orientations. These findings indicated that,
      compared to the classical oblique effect, the horizontal effect with broad-band
      noise stimuli might occur at relatively later stages of visual information
      processing and might involve more complex neural mechanisms.

PMID- 22483936
TI  - Biomarkers of cell death applicable to early clinical trials.
AB  - The development of biomarkers of cell death to reflect tumor biology and drug
      induced response has garnered interest with the development of several classes of
      drugs aimed at decreasing the cellular threshold for apoptosis and exploiting pre
      existing oncogenic stresses. These novel anticancer drugs, directly targeted to
      the apoptosis regulatory machinery and aimed at abrogating survival signaling
      pathways, are entering early clinical trials provoking the question of how to
      monitor their impact on cancer patients. The parallel development of drugs with
      predictive biomarkers and their incorporation into early clinical trials are
      anticipated to support the pharmacological audit trail, to speed the development
      and reduce the attrition rate of novel drugs whose objective is to provoke tumor
      cell death. Tumor biopsies are an ideal matrix to measure apoptosis, but
      surrogate less invasive biomarkers such as blood samples and functional imaging
      are less challenging to acquire clinically. Archetypal and exploratory examples
      illustrating the importance of biomarkers to drug development are given. This
      review explores the substantive challenges associated with the validation,
      deployment, interpretation and utility of biomarkers of cell death and reviews
      recent advances in their incorporation in preclinical and early clinical trial
      contexts.

PMID- 22483937
TI  - MiR-34a inhibits lipopolysaccharide-induced inflammatory response through
      targeting Notch1 in murine macrophages.
AB  - Inflammatory responses are complex events occurring when the host immune system
      fights against invading pathogens, which are double-edged swords requiring
      appropriate control. MicroRNAs (miRNAs), emerging as a new layer of gene
      regulation mechanism, have been reported to have crucial effects on inflammation.
      In the current study, we identified miR-34a, previously known for its potent
      tumor suppressive role, to be a novel inflammation regulator. We found that the
      expression of miR-34a was downregulated in macrophages after lipopolysaccharide
      (LPS) stimulation. MiR-34a mimics decreased, while the inhibition of miR-34a
      increased, the expression of inflammatory cytokines tumor necrosis factor-<alpha>
      (TNF-<alpha>) and interleukin-6 (IL-6) in LPS treated RAW264.7 cells.
      Bioinformatics predictions revealed a potential binding site of miR-34a in 3'
      untranslated region (UTR) of Notch1 and it was further confirmed by luciferase
      assay. Moreover, both the mRNA and protein level of Notch1 were downregulated by
      miR-34a in RAW264.7. Subsequently, knockdown of Notch1 with either genetic or
      pharmacological inhibition exhibited similar effects as miR-34a mimics on LPS
      induced macrophage inflammatory response. Furthermore, the NF-kappaB activation
      induced by LPS was also significantly suppressed by miR-34a. These results
      together identify, for the first time, miR-34a as a negative regulator in LPS
      induced inflammation at least partially by targeting Notch1. Besides extending
      the knowledge of miR-34a from tumor suppressor to inflammation regulator, this
      study also provides an implication that compounds which can enhance miR-34a
      expression or miR-34a itself may hold a promise in anti-inflammatory drugs
      development.

PMID- 22483938
TI  - Sensory regulation of the C. elegans germline through TGF-beta-dependent
      signaling in the niche.
AB  - The proliferation/differentiation balance of stem and progenitor cell populations
      must respond to the physiological needs of the organism [1, 2]. Mechanisms
      underlying this plasticity are not well understood. The C. elegans germline
      provides a tractable system to study the influence of the environment on
      progenitor cells (stem cells and their proliferative progeny). Germline
      progenitors accumulate during larval stages to form an adult pool from which
      gametes are produced. Notch pathway signaling from the distal tip cell (DTC)
      niche to the germline maintains the progenitor pool [3-5], and the larval
      germline cell cycle is boosted by insulin/IGF-like receptor signaling [6]. Here
      we show that, independent of its role in the dauer decision, TGF-beta regulates
      the balance of proliferation versus differentiation in the C. elegans germline in
      response to sensory cues that report population density and food abundance.
      Ciliated ASI sensory neurons are required for TGF-beta-mediated expansion of the
      larval germline progenitor pool, and the TGF-beta receptor pathway acts in the
      germline stem cell niche. TGF-beta signaling thereby couples germline development
      to the quality of the environment, providing a novel cellular and molecular
      mechanism linking sensory experience of the environment to reproduction.

PMID- 22483939
TI  - Arabidopsis touch-induced morphogenesis is jasmonate mediated and protects
      against pests.
AB  - Plants cannot change location to escape stressful environments. Therefore, plants
      evolved to respond and acclimate to diverse stimuli, including the seemingly
      innocuous touch stimulus [1-4]. Although some species, such as Venus flytrap,
      have fast touch responses, most plants display more gradual touch-induced
      morphological alterations, called thigmomorphogenesis [2, 3, 5, 6].
      Thigmomorphogenesis may be adaptive; trees subjected to winds develop less
      elongated and thicker trunks and thus are less likely damaged by powerful wind
      gusts [7]. Despite the widespread relevance of thigmomorphogenesis, the
      regulation that underlies plant mechanostimulus-induced morphological responses
      remains largely unknown. Furthermore, whether thigmomorphogenesis confers
      additional advantage is not fully understood. Although aspects of
      thigmomorphogenesis resemble ethylene effects [8], and touch can induce ethylene
      synthesis [9, 10], Arabidopsis ethylene response mutants show touch-induced
      thigmomorphogenesis [11]; thus, ethylene response is nonessential for
      thigmomorphogenesis. Here we show that jasmonate (JA) phytohormone both is
      required for and promotes the salient characteristics of thigmomorphogenesis in
      Arabidopsis, including a touch-induced delay in flowering and rosette diameter
      reduction. Furthermore, we find that repetitive mechanostimulation enhances
      Arabidopsis pest resistance in a JA-dependent manner. These results highlight an
      important role for JA in mediating mechanostimulus-induced plant developmental
      responses and resultant cross-protection against biotic stress.

PMID- 22483940
TI  - A causal link between visual spatial attention and reading acquisition.
AB  - Reading is a unique, cognitive human skill crucial to life in modern societies,
      but, for about 10% of the children, learning to read is extremely difficult. They
      are affected by a neurodevelopmental disorder called dyslexia. Although impaired
      auditory and speech sound processing is widely assumed to characterize dyslexic
      individuals, emerging evidence suggests that dyslexia could arise from a more
      basic cross-modal letter-to-speech sound integration deficit. Letters have to be
      precisely selected from irrelevant and cluttering letters by rapid orienting of
      visual attention before the correct letter-to-speech sound integration applies.
      Here we ask whether prereading visual parietal-attention functioning may explain
      future reading emergence and development. The present 3 year longitudinal study
      shows that prereading attentional orienting--assessed by serial search
      performance and spatial cueing facilitation--captures future reading acquisition
      skills in grades 1 and 2 after controlling for age, nonverbal IQ, speech-sound
      processing, and nonalphabetic cross-modal mapping. Our findings provide the first
      evidence that visual spatial attention in preschoolers specifically predicts
      future reading acquisition, suggesting new approaches for early identification
      and efficient prevention of dyslexia.

PMID- 22483941
TI  - Optogenetic analysis of a nociceptor neuron and network reveals ion channels
      acting downstream of primary sensors.
AB  - BACKGROUND: Nociception generally evokes rapid withdrawal behavior in order to
      protect the tissue from harmful insults. Most nociceptive neurons responding to
      mechanical insults display highly branched dendrites, an anatomy shared by
      Caenorhabditis elegans FLP and PVD neurons, which mediate harsh touch responses.
      Although several primary molecular nociceptive sensors have been characterized,
      less is known about modulation and amplification of noxious signals within
      nociceptor neurons. First, we analyzed the FLP/PVD network by optogenetics and
      studied integration of signals from these cells in downstream interneurons.
      Second, we investigated which genes modulate PVD function, based on prior single
      neuron mRNA profiling of PVD. RESULTS: Selectively photoactivating PVD, FLP, and
      downstream interneurons via Channelrhodopsin-2 (ChR2) enabled the functional
      dissection of this nociceptive network, without interfering signals by other
      mechanoreceptors. Forward or reverse escape behaviors were determined by PVD and
      FLP, via integration by command interneurons. To identify mediators of PVD
      function, acting downstream of primary nocisensor molecules, we knocked down PVD
      specific transcripts by RNAi and quantified light-evoked PVD-dependent behavior.
      Cell-specific disruption of synaptobrevin or voltage-gated Ca(2+) channels
      (VGCCs) showed that PVD signals chemically to command interneurons. Knocking down
      the DEG/ENaC channel ASIC-1 and the TRPM channel GTL-1 indicated that ASIC-1 may
      extend PVD's dynamic range and that GTL-1 may amplify its signals. These channels
      act cell autonomously in PVD, downstream of primary mechanosensory molecules.
      CONCLUSIONS: Our work implicates TRPM channels in modifying excitability of and
      DEG/ENaCs in potentiating signal output from a mechano-nociceptor neuron. ASIC-1
      and GTL-1 homologs, if functionally conserved, may denote valid targets for novel
      analgesics.

PMID- 22483942
TI  - EB1-recruited microtubule +TIP complexes coordinate protrusion dynamics during 3D
      epithelial remodeling.
AB  - BACKGROUND: Epithelial remodeling, in which apical-basal polarized cells switch
      to a migratory phenotype, plays a central role in development and disease of
      multicellular organisms. Although dynamic microtubules (MTs) are required for
      directed migration on flat surfaces, how MT dynamics are controlled or contribute
      to epithelial remodeling in a more physiological three-dimensional (3D)
      environment is not understood. We use confocal live-cell imaging to analyze MT
      function and dynamics during 3D epithelial morphogenesis and remodeling of
      polarized Madin-Darby canine kidney epithelial cells that undergo partial
      epithelial-to-mesenchymal transition in response to hepatocyte growth factor
      (HGF). RESULTS: We find that HGF treatment increases MT growth rate before
      morphological changes are evident and that large numbers of MTs grow into HGF
      induced cell extensions independent of centrosome reorientation. Using lentivirus
      mediated small hairpin RNA, we demonstrate that EB1, an adaptor protein that
      mediates recruitment of numerous other +TIP proteins to growing MT plus ends, is
      required for this HGF-induced MT reorganization. We further show that protrusion
      and adhesion dynamics are disorganized and that vesicular trafficking to the tip
      of HGF-induced cell extensions is disrupted in EB1-depleted cells. CONCLUSIONS:
      We conclude that EB1-mediated interactions with growing MTs are important to
      coordinate cell shape changes and directed migration into the surrounding
      extracellular matrix during epithelial remodeling in a physiological 3D
      environment. In contrast, EB1 is not required for the establishment or
      maintenance of apical-basal cell polarity, suggesting different functions of
      +TIPs and MTs in different types of cell polarity.

PMID- 22483943
TI  - Effect of site of deposition on the fertility of sheep inseminated with frozen
      thawed semen.
AB  - The widespread use of artificial insemination (AI) in sheep is currently
      prevented due to the lack of a cost effective insemination technique utilising
      frozen-thawed semen. The objective of the present study was to determine if the
      deposition of frozen-thawed semen in the vaginal fornix would result in a
      pregnancy rate comparable to that achieved following cervical insemination.
      Multiparous ewes of various breeds were synchronised and inseminated into either
      the vaginal fornix (n=78) or the cervix (n=79), at 57 h post sponge removal, with
      frozen-thawed semen. Information on mucus secretion and the depth to which it was
      possible to penetrate the cervix at insemination (cervically inseminated ewes
      only) was recorded at the time of AI. Pregnancy rate was subsequently determined
      either by return to service (oestrus) or after slaughter 30 days post
      insemination. Insemination site did not significantly influence pregnancy rate
      using frozen-thawed semen (36.2% compared to 27.6% for cervical and vaginal
      fornix insemination, respectively; P=0.26). Whilst depth of cervical penetration
      was positively associated with pregnancy rate (P<0.05), this association needs to
      be interpreted with caution as none of the ewes where the cervix could not be
      penetrated (score=0) was pregnant. In conclusion, pregnancy rate following
      insemination of frozen-thawed semen into the vaginal fornix was within 10% points
      of that obtained following cervical AI of frozen-thawed semen. As insemination
      into the vaginal fornix is technically easier than cervical insemination, it may
      be more practical for use in large scale applications.

PMID- 22483944
TI  - StarClose arterial closure after conversion from retrograde to antegrade access.

PMID- 22483945
TI  - Differentiation between tuberculosis and lymphoma in mediastinal lymph nodes:
      Evaluation with contrast-enhanced MDCT.
AB  - AIM: To determine the specific imaging criteria on contrast-enhanced
      multidetector computed tomography (MDCT) for differentiating between tuberculosis
      and lymphoma in mediastinal lymph nodes. MATERIALS AND METHODS: The anatomical
      distribution and enhancement patterns of mediastinal lymph nodes on contrast
      enhanced MDCT were reviewed in 37 patients with tuberculosis and 54 patients with
      lymphoma. Of the patients with lymphoma, 18 had Hodgkin's disease and 36 had non
      Hodgkin's lymphoma. RESULTS: Region 10R was involved more often in tuberculosis
      than in Hodgkin's disease and non-Hodgkin's lymphoma. Region 6 had a higher
      tendency to be affected in Hodgkin's disease and non-Hodgkin's lymphoma compared
      with tuberculosis. Tuberculosis showed peripheral enhancement in 78% of cases,
      frequently with a multilocular appearance, compared to Hodgkin's disease and non
      Hodgkin's lymphoma, which showed peripheral enhancement in only 6 and 3% of
      cases, respectively. Homogeneous enhancement was more commonly seen in lymphoma
      (83% for Hodgkin's disease, and 83% for non-Hodgkin's lymphoma) than in
      tuberculosis (8%). In the determination of tuberculosis, results showed that when
      a peripheral enhancement pattern was seen, sensitivity was 78%, specificity was
      96%, and accuracy was 89%. In the determination of lymphoma, results showed that
      when a homogeneous enhancement pattern was seen, sensitivity was 83%, specificity
      was 92%, and accuracy was 87%. CONCLUSION: The findings of the present study
      indicate that specific anatomical distribution and enhancement patterns of
      lymphadenopathy shown on contrast-enhanced MDCT can be useful in differentiating
      tuberculosis from lymphoma of mediastinal lymph nodes.

PMID- 22483946
TI  - Central skull base osteomyelitis as a complication of necrotizing otitis externa:
      Imaging findings, complications, and challenges of diagnosis.
AB  - Central skull base osteomyelitis is a rare, life-threatening complication of
      necrotizing or "malignant" otitis externa (NOE), which results in destruction of
      the skull base. The imaging appearances can be misinterpreted as malignancy but
      consideration of this diagnosis, both radiologically and clinically, is
      imperative to avoid the need for biopsy. The aim of this review is to highlight
      the pertinent imaging findings on computed tomography and magnetic resonance
      imaging as well as the potential complications of this condition.

PMID- 22483947
TI  - Structural and functional analysis of myostatin-2 promoter alleles from the
      marine fish Sparus aurata: evidence for strong muscle-specific promoter activity
      and post-transcriptional regulation.
AB  - Myostatin (MSTN) is a negative regulator of skeletal muscle growth. In contrast
      to mammals, fish possess at least two paralogs of MSTN: MSTN-1 and MSTN-2. In
      this study, we analyzed the structural-functional features of the four variants
      of Sparus aurata MSTN-2 5'-flanking region: saMSTN-2a, saMSTN-2as, saMSTN-2b and
      saMSTN-2c. In silico analysis revealed numerous putative cis regulatory elements
      including several E-boxes known as binding sites to myogenic transcription
      factors. Transient transfection experiments using non-muscle and muscle cell
      lines showed surprisingly high transcriptional activity in muscle cells,
      suggesting the presence of regulatory elements unique to differentiated myotubes.
      These observations were confirmed by in situ intramuscular injections of promoter
      DNA followed by reporter gene assays. Moreover, high promoter activity was found
      in differentiated neural cell, in agreement with MSTN-2 expression in brain.
      Progressive 5'-deletion analysis, using reporter gene assays, showed that the
      core promoter is located within the first -127 bp upstream of the ATG, and
      suggested the presence of regulatory elements that either repress or induce
      transcriptional activity. Transient transgenic zebrafish provided evidence for
      saMSTN-2 promoter ability to direct GFP expression to myofibers. Finally, our
      data shows that although no mature saMSTN-2 mRNA is observed in muscle; unspliced
      forms accumulate, confirming high level of transcription. In conclusion, our
      study shows for the first time that MSTN-2 promoter is a very robust promoter,
      especially in muscle cells.

PMID- 22483948
TI  - Relationship between pollutant content and ecotoxicity of sewage sludges from
      Spanish wastewater treatment plants.
AB  - Chemical and ecotoxicological properties of 28 sewage sludge samples from Spanish
      wastewater treatment plants were studied in order to assess their suitability for
      agricultural purposes. Sludge samples were classified into five categories
      according to specific treatment processes in terms of digestion
      (aerobic/anaerobic) and drying (mechanical/thermal). Composted samples, as
      indicative of the most refined process, were also considered. Sludges were
      subjected to physical-chemical characterization, being the sludge stabilization
      degree respirometrically assessed. The concentrations of seven metals (Cd, Cr,
      Cu, Pb, Zn, Ni, Hg) and organic substances (phenolic compounds, polycyclic
      aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated naphthalenes,
      polybrominated diphenyl ethers, and perfluorinated compounds) were determined.
      Finally, two ecotoxicological tests were performed: i) Microtox(r) toxicity test
      with Vibrio fischeri, and ii) root elongation test with Allium cepa, Lolium
      perenne and Raphanus sativus seeds. Significant differences were found in the
      following parameters: dry matter, electrical conductivity, nitrogen, organic
      matter and its stability, phytotoxicity and ecotoxicity, depending on the sludge
      treatment. In turn, no significant differences were found between categories in
      the concentrations of most metals and organic pollutants, with the exception of
      free phenolic compounds. Furthermore, no correlation between total heavy metal
      burden and ecotoxicity was observed. However, a good correlation was found
      between phenolic compounds and most ecotoxicological tests. These results suggest
      that sludge stability (conditioned by sludge treatment) might have a greater
      influence on sludge ecotoxicity than the pollutant load. Composting was
      identified as the treatment resulting in the lowest toxicity.

PMID- 22483949
TI  - The binding of phenanthrene to engineered silver and gold nanoparticles.
AB  - The steadily rising production and use of engineered nanoparticles (ENP) leads to
      their entry into the aquatic environment. In addition to the various adverse
      effects that have been seen for different organisms, ENP are suspected to
      influence the transport, bioavailability and toxic properties of a range of
      environmental contaminants that may adsorb to their surface. In this study, the
      binding properties of the polycyclic aromatic hydrocarbon phenanthrene to
      stabilized silver and gold ENP were investigated using a novel mass balance based
      single-equilibrium approach. Only citrate coated gold ENP (AuNP(CIT)) were found
      to bind phenanthrene. No binding was observed for polyvinylpyrolidone coated
      silver ENP (AgNP(PVP)) nor citrate coated silver ENP (AgNP(CIT)) suggesting that
      the properties of the core material have a major influence on binding reactions.
      A binding coefficient K(b) was defined as the ratio between the concentration of
      phenanthrene associated to the AuNP(CIT) and that freely dissolved in the
      exposure medium. Temperature was not seen to significantly influence K(b) within
      an environmentally relevant range (4-25  degrees C). The presence of methanol
      significantly reduced or prevented the formation of the AuNP(CIT)-phenathrene
      complex. Results suggest that the binding is a low energy physio-sorption, likely
      associated to a partial displacement or specific arrangement of the citrate
      capping on the gold core.

PMID- 22483950
TI  - Treatment of mandibular angle fractures - linea obliqua plate versus grid plate.
AB  - OBJECTIVES: To compare treatment outcomes, handling and long term results between
      two osseo-fixation systems for mandibular angle fractures - the external oblique
      ridge (external oblique) plate and the grid plate. MATERIAL AND METHODS: Sixty
      patients with mandibular angle fracture were analyzed regarding their operative
      treatment: 30 patients were treated with an external oblique plate and compared
      to 30 patients treated with a grid plate on the vestibular cortex. The follow up
      period was at least 1 year for both groups and the following complications were
      noted: infection, abnormality in fracture healing, nonunion, pain, hypoaesthesia
      and dysocclusion. RESULTS: The overall average operation time (from intubation to
      extubation) was 102.1 min (+/- 44.1 min). Single sided fractures treated with the
      grid plate needed in average 81.07 min (+/- 37.9 min) of operation time while
      single sided fractures treated with the external oblique plate needed 89.3 min
      (+/- 42.2 min). In multiple mandibular fractures, no significant change in the
      operation time between either plating system was found (118.8 +/- 35.2 min).
      After the follow up period fracture healing was considered clinically complete in
      all patients, but complications occurred significantly more often in the external
      oblique group (13.3%; N=8) than in the grid plate group (0%; N=0). CONCLUSION:
      Isolated mandibular angle fractures can be more effectively treated using grid
      plates than using other osteosynthesis techniques. It is an easy to use
      alternative to conventional miniplate systems with good clinical outcome and
      fewer complications. An angulated burr and screwdriver has to be used to put on
      the plate laterally.

PMID- 22483951
TI  - A low-energy intensive electrochemical system for the eradication of Escherichia
      coli from ballast water: process development, disinfection chemistry, and
      kinetics modeling.
AB  - The invasion of biological organisms via ballast water has created threats to the
      environment and human health. In this study, a cost-effective electrochemical
      disinfection reactor was developed to inactivate Escherichia coli, one of the IMO
      regulated indicator microbes, in simulated ballast water. The complete
      inactivation of E. coli could be achieved within a very short time (150, 120, or
      60 s) with an energy consumption as low as 0.0090, 0.0074 or 0.0035 kWh/m(3) for
      ballast water containing E. coli at concentrations of 10(8), 10(7) and 10(6)
      CFU/100 mL, respectively. Electrochemical chlorination was the major disinfection
      mechanism in chloride-abundant electrolytes, whereas oxidants such as ozone and
      free radicals contributed to 20% of the disinfection efficiency in chloride-free
      electrolytes. Moreover, a disinfection kinetics model was successfully developed
      to describe the inactivation of E. coli.

PMID- 22483952
TI  - Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms.
AB  - OBJECTIVE: To examine the potential contribution of the serotonin hydroxylase
      (TPH1 and TPH2) genes, and the serotonin transporter promoter polymorphism
      (5HTTLPR) to the unique and pleiotropic risk of PTSD symptoms and depressive
      symptoms. METHODS: Participants included 200 adults exposed to the 1988 Spitak
      earthquake from 12 multigenerational families (3 to 5 generations). Severity of
      trauma exposure, PTSD, and depressive symptoms were assessed using standard
      psychometric instruments. Pedigree-based variance component analysis was used to
      assess the association between select genes and the phenotypes. RESULTS: After
      adjusting for age, sex, exposure and environmental variables, there was a
      significant association of PTSD symptoms with the 't' allele of TPH1 SNP
      rs2108977 (p<0.004), explaining 3% of the phenotypic variance. This allele also
      showed a non-significant trend for an association with depressive symptoms
      (p=0.08). Also, there was a significant association of PTSD symptoms and the 't'
      allele of TPH2 SNP rs11178997 (p=0.03), explaining 4% of the variance. Depressive
      symptoms were significantly associated with the 's' allele of 5HTTLPR (p=0.03),
      explaining 4% of the variance. LIMITATIONS: Retrospective rating of exposure may
      have been subject to memory failure leading to misestimation of symptom
      severities. Second, findings may not be generalizable to other ethnic/racial
      populations. CONCLUSION: To our knowledge, this is the first published report
      showing that variants in TPH1 and TPH2 genes constitute risk factors for PTSD
      symptoms. Additionally, the TPH1 gene may be associated pleiotropically with PTSD
      and depressive symptoms. The association of the 's' allele of 5HTTLPR
      polymorphism with depression adds to similar findings from case/case-control
      studies.

PMID- 22483953
TI  - Increased suppression of negative and positive emotions in major depression.
AB  - BACKGROUND: Patients with major depression (MDD) show increased suppression of
      negative emotions. Emotion suppression is related to depressive symptoms such as
      depressive mood and anhedonia. It is not clear whether MDD patients also suppress
      positive emotions. In the present study we aim to investigate suppression of both
      negative and positive emotions in MDD patients as well as the relation between
      emotion suppression and depressive symptoms. In addition, we suggest that emotion
      suppression might be associated with fear of emotions. METHODS: 39 MDD patients
      and 41 matched healthy control subjects were investigated for emotion suppression
      and fear of emotions with the Emotion Acceptance Questionnaire (EAQ). In
      addition, we applied additional questionnaires to validate emotion suppression
      findings and to assess depressive symptoms. RESULTS: MDD patients reported
      increased suppression of both negative and positive emotions. Suppression of
      negative and positive emotions was related to depressive symptoms. Patients also
      reported more fear of emotions than healthy subjects and this fear was related to
      emotion suppression in both study samples. LIMITATIONS: Due to the cross
      sectional and correlational study design, causal directions between the variables
      tested cannot be stated. CONCLUSIONS: Fear of emotion might be one reason why MDD
      patients suppress emotions. With regard to positive emotions, our results
      strongly suggest that therapeutic approaches should not only encourage patients
      to participate in potentially enjoyable situations but that patients may also
      benefit from practicing the allowance of pleasant emotions.

PMID- 22483954
TI  - A longitudinal evaluation of religiosity and psychosocial determinants of
      suicidal behaviors among a population-based sample in the United States.
AB  - BACKGROUND: Relationships among religiosity and other psychosocial factors in
      determining suicidal behaviors in adolescence and in emerging adulthood have been
      inconclusive. We sought to investigate prospective relationships among
      religiosity, psychosocial factors and suicidal behaviors using a nationally
      representative sample of adolescents emerging into adulthood. METHOD: Analysis
      was based on 9412 respondents from four waves of National Longitudinal Study of
      Adolescent Health. A Generalized Estimating Equation (GEE) procedure was used to
      fit a series of models on the response variable (suicidal behaviors) and a set of
      psychosocial and religiosity predictors taking into account the correlated
      structure of the datasets. RESULTS: Analyses showed that adolescent suicidality
      and religious activity participation showed significant declines over time. Using
      multinomial logistic regression we found that females showed statistically
      significant risks of suicidal behaviors, but this effect declined in adulthood.
      In adjusted models, baseline attendance of a church weekly was associated with
      42% reduction (95% Confidence Interval: 0.35-0.98) of suicide ideation in Wave
      III. Across all waves, low support from fathers (compared with mothers)
      consistently explained variability in suicidal behaviors among genders emerging
      into adulthood. LIMITATIONS: Accurate measurement of religiosity is
      psychometrically challenging. CONCLUSIONS: The findings of the study indicate
      that religious activity participation is associated with reduced suicidal
      behaviors among adolescents but this effect declines during emerging adulthood.
      Psychosocial supports particularly from fathers' have an enduring impact on
      reduced suicidal behaviors among adolescents and emerging adults. Prevention,
      identification and evaluation of disorders of suicidality need a careful
      assessment of underlying mental pain (psyache) to reduce the likelihood of
      aggravated suicide.

PMID- 22483955
TI  - Suicidality among adults with intellectual disability.
AB  - BACKGROUND: The objective of the current study is to arrive at a better
      understanding of individuals with intellectual disability (ID) who threaten or
      attempt suicide. METHODS: From a sample of 751 adults with ID who experienced a
      crisis, demographic and clinical profiles of 39 adults who threatened to commit
      suicide were compared to 28 adults who attempted suicide. These individuals were
      then compared to 337 adults who behaved aggressively toward others. RESULTS:
      Individuals who attempted suicide appeared similar to those who voiced suicide
      with the exception that suicide attempters were younger and more likely to visit
      the emergency department. Females, higher functioning individuals, and persons
      with a history of self-harm had higher odds of attempting or threatening suicide
      LIMITATIONS: Research findings based on informant reported data, so diagnoses and
      delivery of services in hospital cannot be validated. CONCLUSIONS: Suicidality
      does occur in adults with ID, and can result in emergency department visits and
      hospitalizations. Recognition of variables associated with suicidality among
      those with ID by clinicians may allow for enhanced assessment, treatment services
      and ultimately more positive mental health outcomes for this group.

PMID- 22483956
TI  - Dermatological adverse effects during genotype-1 hepatitis C treatment with the
      protease inhibitors telaprevir and boceprevir. Patient management.

PMID- 22483957
TI  - Dystonic pattern in a fibromyalgia patient: relevance of a biopsychosocial
      rehabilitation approach.
AB  - We present the complex case of a 49-year-old woman who worked as a cook in a
      school cafeteria and has been suffering from widespread pain since 2002. This
      patient showed a very particular gait pattern with hips adduction, flexed hips
      and knees and bilateral equinus foot deformity. Clinical examinations conducted
      by various clinicians, such as physical medicine and rehabilitation (PM&R)
      physicians and neurologists, yielded very different diagnostic hypotheses, each
      being nevertheless quite "logical": fibromyalgia syndrome with dystonia, CNS
      injury, Little's disease, intramedullary spinal cord tumor or multiple sclerosis.
      The only abnormalities observed occurred during the quantitative sensory test
      presenting as severe widespread allodynia to cold and hot temperatures and during
      Laser Evoked Potentials shown as a dysfunctional pattern for central processing
      of nociceptive data. Gait analysis showed that parameters were in the norms.
      Considering these different tests and the excellent progression of the patient's
      gait and general posture, we must envision that the fibromyalgia syndrome
      hypothesis remained the most likely one. The generalized dystonia was probably
      due to the patient's analgesic protective attitude. The actual therapy is still
      based on the biopsychosocial approach.

PMID- 22483958
TI  - Understanding counterfactuals in discourse modulates ERP and oscillatory gamma
      rhythms in the EEG.
AB  - This study provides ERP and oscillatory dynamics data associated with the
      comprehension of narratives involving counterfactual events. Participants were
      given short stories describing an initial situation ("Marta wanted to plant
      flowers in her garden...."), followed by a critical sentence describing a new
      situation in either a factual ("Since she found a spade, she started to dig a
      hole") or counterfactual format ("If she had found a spade, she would have
      started to dig a hole"), and then a continuation sentence that was either related
      to the initial situation ("she bought a spade") or to the new one ("she planted
      roses"). The ERPs recorded for the continuation sentences related to the initial
      situation showed larger negativity after factuals than after counterfactuals,
      suggesting that the counterfactual's presupposition - the events did not occur -
      prevents updating the here-and-now of discourse. By contrast, continuation
      sentences related to the new situation elicited similar ERPs under both factual
      and counterfactual contexts, suggesting that counterfactuals also activate
      momentarily an alternative "as if" meaning. However, the reduction of gamma power
      following counterfactuals, suggests that the "as if" meaning is not integrated
      into the discourse, nor does it contribute to semantic unification processes.

PMID- 22483959
TI  - Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously
      hypertensive rats.
AB  - Increased blood pressure in hypertension is hypothesized to be caused by high
      sympathetic nervous system (SNS) activity. Since Ang (1-7) exerts an inhibitory
      neuromodulatory effect on the SNS through a NO-mediated mechanism, we tested the
      hypothesis that Ang (1-7) alters centrally nitric oxide synthase (NOS) activity
      and expression in spontaneously hypertensive rats (SHR). Since NOS activity is
      altered in relation to the development of hypertension in rats, we evaluated the
      effect of Ang-(1-7) on hypothalamic NOS activity in two different ages in SHR,
      corresponding to a prehypertensive phase (3-4 weeks) and a established
      hypertension (13-14 weeks) and compared with age-matched Wistar-Kyoto (WKY) rats.
      NOS activity was measured by the conversion of [3H]L-arginine to citrulline. Ang
      (1-7) caused an impairment in NOS activity in prehypertensive SHR (26 +/- 4%
      reduction), while it induced an increase in NOS activity at established
      hypertension (48 +/- 9% increase). In contrast, Ang-(1-7) did not modify NOS
      activity in age-matched WKY rats. In another set of experiments, Ang-(1-7) was
      injected into the anterior hypothalamic area, mean arterial blood pressure (MAP)
      was registered and after 30, 60 and 180 min nNOS expression was evaluated by
      Western-blot. Ang-(1-7) decreased MAP after 10 min of injection and this effect
      was blocked by a NOS inhibitor. nNOS expression increased after 180 min of Ang-(1
      7) intrahypothalamic injection in both WKY and SHR (WKY: 3.6-fold increase above
      basal; SHR: 1.85-fold increase above basal). Our results suggest that Ang-(1-7)
      upregulates hypothalamic NOS in a hypertensive state as a compensatory and
      protective mechanism to combat hypertension.

PMID- 22483960
TI  - Immunohistochemical study of arginase-1 in the spinal cords of Lewis rats with
      experimental autoimmune encephalomyelitis.
AB  - Arginase-1, a marker for M2 phenotype alternatively activated macrophages,
      inhibits inflammation and is associated with phagocytosis of cell debris and
      apoptotic cells. We analyzed the expression of arginase-1, a competitive enzyme
      of inducible nitric oxide synthase (iNOS), in the spinal cords of Lewis rats with
      experimental autoimmune encephalomyelitis (EAE). Western blot analysis showed
      that both arginase-1 and iNOS significantly increased in the spinal cords of rats
      at the peak stage of EAE compared with the expression level in control animals
      (p<0.05) and declined thereafter. Immunofluorescent staining demonstrated that
      increased expression of arginase-1 in EAE spinal cords was confirmed in
      macrophages as well as in some neurons and astrocytes that were constitutively
      positive for arginase-1 in normal spinal cords. A semiquantitative analysis by
      immunofluorescence showed that in EAE lesions, an increased level of arginase-1
      immunoreactivity was matched with ED1-positive macrophages, which were also
      positive for activin A, a marker for the M2 phenotype. Taking all of these
      findings into consideration, we postulate that the increased level of arginase-1,
      which is partly from M2 macrophages, contributes to the modulation of
      neuroinflammation in EAE lesions, possibly through the reduction of nitric oxide
      in the lesion via competition with iNOS for the use of L-arginine.

PMID- 22483961
TI  - Fibronectin supports neurite outgrowth and axonal regeneration of adult brain
      neurons in vitro.
AB  - The molecular basis of axonal regeneration of central nervous system (CNS)
      neurons remains to be fully elucidated. In part, this is due to the difficulty in
      maintaining CNS neurons in vitro. Here, we show that dissociated neurons from the
      cerebral cortex and hippocampus of adult mice may be maintained in culture for up
      to 9 days in defined medium without added growth factors. Outgrowth of neurites
      including axons was observed from both CNS sources and was significantly greater
      on plasma fibronectin than on other substrata such as laminin and merosin.
      Neurite outgrowth on fibronectin appears to be mediated by alpha5beta1 integrin
      since a recombinant fibronectin fragment containing binding sites for this
      receptor was as effective as intact fibronectin in supporting neurite outgrowth.
      Conversely, function-blocking antibodies to alpha5 and beta1 integrin sub-units
      inhibited neurite outgrowth on intact fibronectin. These results suggest that the
      axonal regeneration seen in in vivo studies using fibronectin-based matrices is
      due to the molecule itself and not a consequence of secondary events such as
      cellular infiltration. They also indicate the domains of fibronectin that may be
      responsible for eliciting this response.

PMID- 22483962
TI  - Reproductive experience facilitates recovery from kainic acid-induced neural
      insult in female Long-Evans rats.
AB  - The hormones of pregnancy and lactation (e.g., estrogen, progesterone, and
      oxytocin) have been shown to modulate learning, memory, and the restructuring of
      brain areas not traditionally associated with maternal behavior. Given the impact
      of reproductive experience on plasticity of brain areas such as the hippocampus,
      kainic acid (KA) was used in the current study to induce hippocampal-specific
      neurotoxic insult in adult multiparous and virgin Long-Evans rats. In Experiment
      I, Fluoro-Jade B, an indicant of degenerating cells, revealed significant
      neuronal damage in KA-treated hippocampi at 16 h post-injection in both maternal
      and virgin rats. In Experiment II, maternal and virgin rats were assessed in
      spatial and novel object preference tasks to determine the effects of KA on
      subsequent behavioral and cognitive responses. Twenty-four hours post injection,
      saline maternal animals exhibited superior memory in a spatial task. Further,
      maternal saline-injected rats were more similar to maternal KA-injected rats than
      both the virgin groups. Forty-eight hours following the KA or saline injection,
      compared to virgins, maternal animals demonstrated enhanced memory in the novel
      object memory test, regardless of type of injection. Further, neurobiological
      assessments in Experiment II indicated that virgin KA exposed rats had
      significantly more glial fibrillary acidic protein (GFAP)-immunoreactivity in the
      hippocampus, suggesting that they were in an earlier stage of neural recovery
      compared to maternal animals or, alternatively, may have exhibited more trauma
      than maternal animals. Together, these data suggest that the previously reported
      plasticity of the maternal brain may facilitate neural and behavioral recovery
      from neural insults.

PMID- 22483963
TI  - Possible genetic and epigenetic links between human inner speech, schizophrenia
      and altruism.
AB  - Unique mental abilities have been crucial for evolutionary success of Homo
      sapiens and for the development of his complex social organization. However,
      these abilities have also become a target for mental disorders which often result
      in a reduced fitness and in conflicts between the individual and the conventions
      of society. To account for this evolutionary maladaptation, we advance a new
      concept: that of "mis-exaptation", derived from SJ Gould and E Vrba's concept of
      exaptation. Mis-exaptation is a characteristic which, although it may confer
      positive effects in one field of activity, may reach an inappropriate degree of
      specialisation to have deleterious effects in that or in another field thereby
      leading to a decrease in fitness of the individual. This paper considers "inner
      speech" as an exaptation. Although inner speech is usually a positive aid to
      learning and reasoning, it may also favour the emergence of mental disturbances,
      such as the auditory hallucinations which are characteristic of schizophrenia.
      There is, nevertheless, a possible evolutionary value in mis-exaptational inner
      speech; two traits associated with the mis-exapted state would be altruistic
      behaviour and heightened creativity, the latter being over-expressed in relatives
      of schizophrenic patients. A possible solution for the evolutionary-genetic
      paradox posed by altruism and schizophrenia arising from mis-exaptation will be
      suggested in the light of a cryptic genetic repertoire. A selection of
      illustrative examples of each of these mental states is presented as they appear
      in the pages of the European literature. This article is part of a Special Issue
      entitled: Brain Integration.

PMID- 22483964
TI  - [Brain imaging of infantile autism].
AB  - Understanding of brain structural anomalies seen in children with autism has
      considerably progressed since the apparition of MRI and functional imaging. All
      the results are converging toward the description of anatomical and functional
      anomalies in the regions of the so-called "social brain". Statistical analyses
      show diminution of gray matter in the region of the superior temporal sulcus
      (STS). Functional studies with PET shows a diminution of brain blood flow at rest
      in the same region. Brain activation studies show absence of activation of the
      specialized region in processing human voice and hypoactivation of "social brain"
      regions in complex tasks of social cognition. At last, abnormal connectivity
      between the frontal and temporal regions has been showed. Those regions are
      implicated in processing sensorial inputs necessary for normal social life. All
      those anomalies could be responsible of the abnormal social behaviour pattern of
      children with autism.

PMID- 22483965
TI  - Amino acid, dipeptide and pseudodipeptide conjugates of ring-substituted 8
      aminoquinolines: synthesis and evaluation of anti-infective, beta-haematin
      inhibition and cytotoxic activities.
AB  - Three new series of 8-aminoquinolines with modifications in the side-chain by
      conjugation with amino acids, dipeptides and pseudodipeptides have been
      synthesized. The synthesized compounds were tested for in vitro antimalarial
      activity against chloroquine-sensitive and chloroquine-resistant Plasmodium
      falciparum strains, in vitro cytotoxicity in mammalian kidney cells (Vero), in
      vitro antileishmanial activity against Leishmania donovani, in vitro
      antimicrobial activity and in vitro inhibition of beta-haematin formation. The
      promising compounds were also evaluated for in vivo blood-schizontocidal
      antimalarial activity against Plasmodium berghei infected mice. The analogues 55
      and 101 produced highest antimalarial activities, in vitro. Analogues 52 and 59
      exhibited promising antileishmanial and broad spectrum of antifungal activities,
      respectively.

PMID- 22483966
TI  - Novel glycolipid TLR2 ligands of the type Pam2Cys-alpha-Gal: synthesis and
      biological properties.
AB  - A more complete understanding of the mechanism of action of TLR agonists has
      fueled the investigation of new synthetic immunoadjuvants. In this context, we
      designed and synthesized glycolipids of the type Pam(2)Cys-alpha-Galactose as
      novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3
      bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure
      required for TLR2 agonist activity, by addition of a hydrophilic head, either an
      alpha-Galactosylpyranose or an alpha-Galactosylfuranose to gain respectively
      Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an
      unexpected stereoselectivity was observed during a halide ion-catalytic process
      on a protected galactofuranose: the alpha anomer was obtained with surprisingly
      high selectivity (alpha/beta ratio>9) and with good isolated yield (51%). The
      TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated.
      Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was
      also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of
      TLRs. Moreover, the maturation state of murine dendritic cells previously
      incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry
      and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf
      were found to be equivalent TLR2 agonists, and induced splenocyte proliferation
      and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were
      also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell
      proliferation. This represents the first time a glucidic head has been added to
      the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining
      the immunomodulating activity. This should greatly enrich the data available on
      Pam(2)C structure/activity relationships.

PMID- 22483967
TI  - Rational design, synthesis and anti-proliferative properties of new CB2 selective
      cannabinoid receptor ligands: an investigation of the 1,8-naphthyridin-2(1H)-one
      scaffold.
AB  - CB2 receptor ligands are becoming increasingly attractive drugs due to the
      potential role of this receptor in several physiopathological processes. Using
      our previously described series of 1,8-naphthyridin-2(1H)-on-3-carboxamides as a
      lead class, several nitrogen heterocyclic derivatives, characterized by different
      central cores, were synthesized and tested for their affinity toward the human
      CB1 and CB2 cannabinoid receptors. The obtained results suggest that the new
      series of quinolin-2(1H)-on-3-carboxamides, 4-hydroxy-2-oxo-1,2-dihydro-1,8
      naphthyridine-3-carboxamides and 1,2-dihydro-2-oxopyridine-3-carboxamides
      represent novel scaffolds very suitable for the development of promising CB2
      ligands. Furthermore, the newly synthesized CB2 ligands inhibit proliferation of
      several cancer cell lines. In particular, it was demonstrated that in DU-145 cell
      line these ligands exert a CB2-mediated anti-proliferative action and decrease
      the CB2 receptor expression levels.

PMID- 22483968
TI  - Insights into the binding of the drugs diclofenac sodium and cefotaxime sodium to
      serum albumin: calorimetry and spectroscopy.
AB  - Understanding physical chemistry underlying drug-protein interactions is
      essential to devise guidelines for the synthesis of target oriented drugs.
      Binding of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF) and an
      antibiotic drug, cefotaxime sodium (CFT) belonging to the family of
      cephalosporins with bovine serum albumin (BSA) has been examined using a
      combination of isothermal titration calorimetry (ITC), differential scanning
      calorimetry (DSC), steady state and time resolved fluorescence and circular
      dichroism spectroscopies. Binding affinity of both DCF and CFT with BSA is
      observed to be of the order of 10(4)M(-1), with the binding profiles fitting well
      to the single set of binding site model. The disagreement between calorimetric
      and van't Hoff enthalpies indicates non-adherence to a two-state binding process
      which could be attributed to changes in the conformation of the protein upon
      ligand binding as well as with increase in the temperature. Circular dichroism
      and the fluorescence results, however, do not show any major conformational
      changes upon binding of these drugs to BSA, and hence the discrepancy could be
      due to temperature induced conformational changes in the protein. The results of
      ionic strength dependence and binding in the presence of anionic, cationic and
      non-ionic surfactants indicate, involvement of more that a single type of
      interaction in the binding process. The ITC results for the binding of these
      drugs to BSA in presence of each other indicate that the binding sites for the
      two drugs are different, and therefore binding of one is not influenced by the
      other. The DSC results provide quantitative information on the effect of these
      drugs on the stability of serum albumin. The combined calorimetric and
      spectroscopic approach has provided a detailed analysis including thermodynamics
      of the binding of DCF and CFT with BSA qualitatively and quantitatively.

PMID- 22483969
TI  - Application of indocyanine green videoangiography in surgery for spinal vascular
      malformations.
AB  - We present our recent experience with indocyanine green videoangiography (ICGVA)
      in intra-operative evaluation of two patients with dorsal spinal dural
      arteriovenous fistula (SDAVF) and one patient with conus medullaris arteriovenous
      malformation (AVM). To our knowledge, the latter is the first report of this in
      the literature. Intra-operative ICGVA was used to identify an early filling
      vessel and to obliterate the site of fistulous connection. This was confirmed by
      a repeat ICGVA study and correlated with post-operative digital subtraction
      angiography (DSA). The abnormal fistulous site was identified in all three
      patients and disconnected. Complete obliteration was confirmed in all patients
      using ICGVA and with post-operative imaging. There was no untoward reaction to
      the dye injection. We conclude that ICGVA is a useful adjunct in surgical
      treatment of spinal vascular malformations since it is a real-time, non-invasive,
      radiation-free technique with good image resolution, and is repeatable and easily
      reproducible. Technical disadvantages can be minimized by proper exposure of the
      operative field.

PMID- 22483970
TI  - Prediction of flow augmentation and complications of extracranial-intracranial
      bypass in symptomatic cerebrovascular diseases.
AB  - Augmentation of the cerebral blood supply to correct cerebral hemodynamic
      insufficiency by extracranial-intracranial bypass may be an appropriate method to
      reduce the risk of ischemic stroke. Eighty-five patients with ischemic symptoms,
      decreased regional cerebral blood flow, and decreased regional cerebrovascular
      reactivity were recruited for surgery. The post-bypass mean regional blood flow
      increased by 35.8% compared to the pre-bypass value (p<0.001). Only minor re
      establishment of vasculature after anastomosis was detected in three of four
      patients with middle cerebral artery stenosis, which suggests that there are
      fewer benefits of bypass surgery in this situation. Cerebral infarction occurred
      immediately post-operation in one patient who was predisposed to stroke due to a
      bilateral carotid occlusion. Hyperperfusion injury was infrequent in this series;
      only one patient developed intracerebral hemorrhage three weeks after the bypass.
      One ischemic and one hemorrhagic stroke occurred during the 90 months following
      surgery.

PMID- 22483971
TI  - Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in
      Chinese patients with congenital bilateral absence of vas deferens.
AB  - BACKGROUND: Genetic testing of the cystic fibrosis transmembrane conductance
      (CFTR) gene is currently performed in patients with congenital bilateral absence
      of vas deferens (CBAVD). This study was conducted to investigate the role of
      mutations in the CFTR gene in CBAVD-dependent male infertility. METHODS: 73
      Chinese patients diagnosed with CBAVD were studied. The entire coding regions and
      splice sites of 27 exons of the CFTR gene were sequenced in 146 chromosomes from
      the 73 CBAVD patients. Screening was carried out using PCR, gel electrophoresis
      and DNA sequencing to identify novel variants of the entire coding regions and
      boundaries of the 27 exons. RESULTS: Five novel nonsynonymous mutations, three
      novel splice site mutations and one deletion were identified by sequencing. Apart
      from the novel variants, we also found 19 previously reported mutations and
      polymorphism sites. Thirty-four patients (46.57%) had the 5T variant (6
      homozygous and 28 heterozygous) and in two of them it was not associated with any
      detectable mutation of the CFTR gene. All potential pathogenic mutations are not
      contained in the 1000 Genome Project database. In total, the present study
      identified 30 potential pathogenic variations in the CFTR gene, 9 of which had
      not previously been described. CONCLUSIONS: Most patients with CBAVD have
      mutations in the CFTR gene. A mild genotype with one or two mild or variable
      mutations was observed in all the patients. These findings improve our
      understanding of the distribution of CFTR alleles in CBAVD patients and will
      facilitate the development of more sensitive CFTR mutation screening.

PMID- 22483972
TI  - Right ventricular dysfunction in adolescents with mild cystic fibrosis.
AB  - BACKGROUND: In cystic fibrosis (CF) patients the right ventricle (RV) suffers a
      progressive deterioration, but it is not clear when these changes begin. The aim
      of this study was to analyze the RV function in CF patients with mild respiratory
      disease. METHODS: Color-Doppler-Echocardiographic studies were prospectively
      performed in CF adolescent patients and an age-matched control group. Findings
      were correlated with pulmonary function tests (PFT), genotype, chronic bacterial
      colonization, pancreatic status and clinical scores. Only patients with mild CF
      were selected. RESULTS: Thirty seven CF patients and 40 healthy controls were
      recruited. In CF patients all echocardiographic parameters were abnormal compared
      to controls. Doppler analysis showed slightly elevated pulmonary artery pressure
      values, and abnormal relaxation and systolic function for all indexes. No
      correlation was found with any of the features studied. CONCLUSIONS: In CF
      patients, abnormalities in the structure and function of the RV may be present at
      early stages of the disease. These abnormalities are subclinical and do not
      correlate with clinical scores, PFT, genotype, chronic bacterial colonization or
      pancreatic insufficiency.

PMID- 22483973
TI  - When fear forms memories: threat of shock and brain potentials during encoding
      and recognition.
AB  - The anticipation of highly aversive events is associated with measurable
      defensive activation, and both animal and human research suggests that stress
      inducing contexts can facilitate memory. Here, we investigated whether encoding
      stimuli in the context of anticipating an aversive shock affects recognition
      memory. Event-related potentials (ERPs) were measured during a recognition test
      for words that were encoded in a font color that signaled threat or safety. At
      encoding, cues signaling threat of shock, compared to safety, prompted enhanced
      P2 and P3 components. Correct recognition of words encoded in the context of
      threat, compared to safety, was associated with an enhanced old-new ERP
      difference (500-700 msec; centro-parietal), and this difference was most reliable
      for emotional words. Moreover, larger old-new ERP differences when recognizing
      emotional words encoded in a threatening context were associated with better
      recognition, compared to words encoded in safety. Taken together, the data
      indicate enhanced memory for stimuli encoded in a context in which an aversive
      event is merely anticipated, which could assist in understanding effects of
      anxiety and stress on memory processes.

PMID- 22483974
TI  - Ecdysteroid levels changed by permethrin action in female Rhipicephalus
      sanguineus (Latreille, 1806) (Acari: Ixodidae) ticks.
AB  - As recent studies have shown that ecdysteroids may play a major role in the
      regulation of vitellogenesis in Ixodidae, the present study quantified, by means
      of a radioimmunoassay, the levels of ecdysteroids present in the hemolymph of
      semi-engorged females of Rhipicephalus sanguineus ticks obtained from control
      females (exposed to distilled water) and those exposed to increasing
      concentrations of permethrin. The levels of ecdysteroids decreased significantly
      as the concentration of permethrin increased, suggesting that this compound could
      be an inhibitor of ecdysteroids secretion, and consequently interfering with the
      reproductive ability of these ticks, since this hormone is responsible for the
      synthesis and incorporation of vitellogenin by oocytes. This study complements
      the previous results with R. sanguineus semi-engorged females, showing that
      permethrin is a potent agent causing major morphological changes in tick oocytes,
      such as the appearance of large vacuoles in the cytoplasm, reduction in the
      amount of yolk granules and a decrease in oocyte size, thus culminating in cell
      death and consequently reducing or preventing reproduction in treated females.
      The findings that permethrin leads to a decrease in ecdysteroid titers could
      represent an entry step into this scenario.

PMID- 22483975
TI  - Influence of the 5-HTR1A C-1019G polymorphism on clinical phenotypes of autism
      spectrum disorders.

PMID- 22483976
TI  - Vascular effects of intravenous intralipid and dextrose infusions in obese
      subjects.
AB  - Hyperglycemia and elevated free fatty acids (FFA) are implicated in the
      development of endothelial dysfunction. Infusion of soy-bean oil-based lipid
      emulsion (Intralipid(r)) increases FFA levels and results in elevation of blood
      pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects
      of combined hyperglycemia and high FFA on BP, endothelial function and
      carbohydrate metabolism are not known. Twelve obese healthy subjects received
      four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40
      mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by
      1.03+/-0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during
      saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose
      and insulin concentrations significantly increased after dextrose and combined
      Intralipid and dextrose (all, p<0.05) and were not different from baseline during
      saline and lipid infusion. Intralipid increased systolic BP by 12+/-9 mmHg
      (p<0.001) and diastolic BP by 5+/-6 mmHg (p=0.022),and decreased flow-mediated
      dilatation (FMD) from baseline by 3.2%+/-1.4% (p<0.001). Saline and dextrose
      infusion had neutral effects on BP and FMD. The co-administration of lipid and
      dextrose decreased FMD by 2.4%+/-2.1% (p=0.002) from baseline, but did not
      significantly increase systolic or diastolic BP. Short-term Intralipid infusion
      significantly increased FFA and BP; in contrast, FFA and BP were unchanged during
      combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose
      infusion resulted in endothelial dysfunction similar to Intralipid alone.

PMID- 22483977
TI  - Evidence that sex chromosome genes affect sexual differentiation of female sexual
      behavior.
AB  - Female receptivity including the immobile hormone-dependent lordosis posture is
      essential for successful reproduction in rodents. It is well documented that
      lordosis is organized during the perinatal period when the actions of androgens
      decrease the males' ability to display this behavior in adulthood. Conversely the
      absence of androgens, and the presence of low levels of prepubertal estrogens,
      preserve circuitry that regulates this behavior in females. The current study set
      out to determine whether sex chromosomal genes are involved in the
      differentiation of this behavior. An agonadal mouse model was used to test this
      hypothesis. The SF-1 gene (Nr5a1) is required for development of gonads and
      adrenal glands, and knockout mice are consequently not exposed to endogenous
      gonadal steroids. Thus contributions of sex chromosome genes can be disassociated
      from the actions of estrogens. Use of this model reveals a direct genetic
      contribution from sex chromosomes in the display of lordosis and other female
      typical sexual behavior patterns. It is likely that the concentrations of gonadal
      steroids present during normal male development modify the actions of sex
      chromosome genes on the potential to display female sexual behavior.

PMID- 22483978
TI  - Bio-mediated synthesis of TiO2 nanoparticles and its photocatalytic effect on
      aquatic biofilm.
AB  - The nano-TiO(2) was synthesized biologically employing Bacillus subtilis
      (FJ460362). These nanoparticles were characterized by FTIR, TGA-DTA, UV-Visible
      spectroscopy, XRD and TEM. FTIR and TGA results confirm that the organic
      impurities were completely removed while calcinating the resultant products. Band
      gap value was estimated from the UV-Visible spectrum and anatase crystal phase
      was confirmed by XRD. TEM images reveal that these particles were agglomerated;
      mostly spherical in shape with an average particle size of 10-30nm. The
      synthesized nano-TiO(2) particles were coated on glass slides, biofilm were grown
      and subjected to irradiation of polychromatic light to understand photocatalytic
      activity in controlling the aquatic biofilm. The bacterial killing process was
      established by Epi-fluorescence microscopy. The results reveal that biogenic
      TiO(2) nanomaterial acts as good photocatalyst by the generation of H(2)O(2) in
      the vicinity of the TiO(2)-biofilm interfaces to suppress the growth of the
      aquatic biofilm.

PMID- 22483979
TI  - Anti-inflammatory effect of Lycium Fruit water extract in lipopolysaccharide
      stimulated RAW 264.7 macrophage cells.
AB  - Lycium Fruit has been used as a traditional drug for low back pain and chronic
      cough in east-Asian countries. However, inhibitory effects of Lycium Fruit water
      extract (LFWE) on inflammation remain unknown. In this study, we investigated the
      inhibitory effects of LFWE on pro-inflammatory mediator production in
      lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. LFWE inhibited LPS-induced
      nitric oxide (NO), prostaglandin (PG) E2, tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6 production as well as their synthesizing enzyme inducible
      nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 gene expression.
      Furthermore, LFWE inhibited phosphorylations of extracellular signal-regulated
      kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein
      kinases (MAPKs) as well as suppression of IkappaBalpha degradation and nuclear
      translocation of nuclear factor (NF)-kappaB upon LPS stimulation. In addition,
      LFWE suppressed NO, PGE2, TNF-alpha and IL-6 production in LPS-stimulated
      peritoneal macrophage cells. Taken together, our results suggest that LFWE
      inhibits the production of various inflammatory mediators via blockade on the
      MAPKs and NF-kappaB pathways. This finding first explains the mechanism of anti
      inflammatory effect by LFWE in LPS-stimulated macrophage cells.

PMID- 22483980
TI  - Average consensus in networks of dynamic multi-agents with switching topology:
      infinite matrix products.
AB  - This paper deals with the average consensus problem in a multi-agent system with
      switching interaction topology modeled as a weighted digraph. The convergence
      analysis is performed in both discrete-time and continuous-time dynamics based on
      the theory of infinite matrix products. Conditions for system convergence to
      average consensus are derived in the form of constraints on direct and reverse
      graphs and the structure of adjacency elements among the agents. Furthermore, a
      sufficient condition is provided for convergence to average consensus in systems
      in which the interaction topology is balanced over infinite contiguous non
      overlapping time intervals instead of being balanced continuously. Numerical
      simulations are given to demonstrate the effectiveness of the theoretical
      results.

PMID- 22483981
TI  - Glucocorticoid receptor mediated suppression of natural killer cell activity:
      identification of associated deacetylase and corepressor molecules.
AB  - Physical and psychological stressors reduce natural killer cell function. This
      reduction in cellular function results from stress-induced release of
      glucocorticoids. Glucocorticoids act upon natural killer cells to deacetylate and
      transrepress immune response genes through epigenetic processes. However, other
      than the glucocorticoid receptor, the proteins that participate in this process
      are not well described in natural killer cells. The purpose of this study was to
      identify the proteins associated with the glucocorticoid receptor that are likely
      epigenetic participants in this process. Treatment of natural killer cells with
      the synthetic glucocorticoid, dexamethasone, produced a significant time
      dependent reduction in natural killer cell activity as early as 8h post
      treatment. This reduction in natural killer cell activity was preceded by nuclear
      localization of the glucocorticoid receptor with histone deacetylase 1 and the
      corepressor, SMRT. Other class I histone deacetylases were not associated with
      the glucocorticoid receptor nor was the corepressor NCoR. These results
      demonstrate histone deacetylase 1 and SMRT to associate with the ligand activated
      glucocorticoid receptor within the nuclei of natural killer cells and to be the
      likely participants in the histone deacetylation and transrepression that
      accompanies glucocorticoid mediated reductions in natural killer cell function.

PMID- 22483982
TI  - Development of a highly sensitive gold nanoparticle probe-based assay for
      bluetongue virus detection.
AB  - A simple gold nanoparticle (GNP) probe based assay (GNPA) that was modified from
      a bio-barcode assay (BCA) technique, was developed for ultra-sensitive, rapid
      detection of the bluetongue virus (BTV) VP7 outer-core protein. This assay
      captures the VP7 target antigen using the GNP probe coated with anti-VP7
      polyclonal antibodies and single-stranded signal DNA. Magnetic microparticle
      (MMP) probes coated with anti-VP7 monoclonal antibodies were then added to form a
      sandwich immuno-complex. The single-stranded signal DNA coated onto the GNP probe
      present in the immuno-complex could then be detected by PCR and real-time
      fluorescence PCR using a TaqMan probe. The assay has a purified VP7 detection
      limit of 10(-2)fg/ml which is 8 orders of magnitude greater than that of
      conventional antigen capture ELISAs and 1 order of magnitude more sensitive than
      that of a conventional BCA. These results indicate that the GNPA is a highly
      sensitive method for easy detection of BTV proteins and that it can be modified
      as needed to measure the presence of other proteins.

PMID- 22483983
TI  - Hyperthermia induces cytoskeletal alterations and mitotic catastrophe in p53
      deficient H1299 lung cancer cells.
AB  - Hyperthermia is used in cancer therapy, however much remains to be discovered
      regarding its mechanisms of action at the cellular level. In this study, the
      effects of hyperthermia on cell death, survival, morphology and the cytoskeleton
      were investigated in a non-small cell lung cancer cell line, H1299. Despite the
      fact that this cell line is widely used in research, it has not yet been tested
      for heat shock sensitivity. Cells were given a 30-min heat shock at 43.5 degrees
      C and 45 degrees C and left to recover at 37 degrees C for 24 and 48 h. 24 h
      after heat shock treatment, we monitored changes in the organization of the
      cytoskeleton using immunofluorescence microscopy. The number of actin stress
      fibers was significantly reduced, microtubules formed a looser meshwork, a
      portion of the cells possessed multipolar mitotic spindles, whereas vimentin
      filaments collapsed into perinuclear complexes. 48 h following heat stress, most
      of the cells showed recovery of the cytoskeleton, however we observed a
      considerable number of giant cells that were multinucleated or contained one
      enlarged nucleus. The data obtained by MTT assay showed a dose-dependent decrease
      of cell viability, while flow cytometric analysis revealed an increase in the
      number of cells with externalized phosphatidylserine. The results suggest that
      one of the modes of heat-induced cell death in H1299 cells is mitotic
      catastrophe, which probably ends in apoptosis.

PMID- 22483984
TI  - High-performance liquid chromatography quadrupole time-of-flight mass
      spectrometry method for the analysis of antidiabetic drugs in aqueous
      environmental samples.
AB  - Antidiabetic compounds are among the most prescribed pharmaceuticals.
      Nevertheless, their presence in the environment has been scarcely evaluated as
      there is no method for their determination in environmental samples. This paper
      reports the development of an analytical method for the determination of
      traditionally used antidiabetics (metformin and glibenclamide) and novel
      antidiabetics (vildagliptin, sitagliptin and pioglitazone). The method is based
      on solid-phase extraction and determination by high-performance liquid
      chromatography quadrupole time-of-flight mass spectrometry. The method was
      applied to effluent wastewater, river water and tap water. Mean recoveries of
      glibenclamide, vildagliptin, sitagliptin and pioglitazone in the matrices
      evaluated were in the range 78-83%; limits of quantification were in the range
      0.4-4.3 ng L(-1); and precision values were in the range 2.2-13%. The high
      hydrophilicity and polarity of metformin complicated its simultaneous extraction.
      Chromabond Tetracycline cartridges and sample pH 8.5 were applied to the
      extraction of glibenclamide, vildagliptin, sitagliptin and pioglitazone. Oasis
      HLB cartridges, neutral sample pH and SDS as ion-pair reagent were used for the
      extraction of metformin. Validation results of metformin were not as favorable as
      those of the other antidiabetic drugs but were comparable with others previously
      reported. The developed method was applied to the first-time determination of the
      concentrations of the five antidiabetic drugs in wastewater, river water and tap
      water. Metformin was the antidiabetic drug at the highest concentration in
      wastewater and surface water (up to 253 ng L(-1) and 104 ng L(-1), respectively).
      Two of the antidiabetic drugs of recent prescription, sitagliptin and
      vildagliptin, were found in effluent wastewater at concentrations of 117 ng L(-1)
      and 12 ng L(-1), respectively, and in river water at concentrations of 35 ng L(
      1) and 6 ng L(-1), respectively, whereas the classic antidiabetic drug
      glibenclamide and the novel drug pioglitazone were not detected.

PMID- 22483985
TI  - Residual metals cause variability in methionine oxidation measurements in protein
      pharmaceuticals using LC-UV/MS peptide mapping.
AB  - Methionine oxidation has been demonstrated to play an important role in protein
      stability in vitro and in vivo. It may also cause changes in biological activity
      and immunogenicity profile of therapeutic proteins. Therefore, it is critical to
      monitor methionine oxidation in biopharmaceuticals during process and formulation
      development, as well as long-term stability studies. A common analytical method
      for methionine oxidation determination is peptide mapping analysis of protein
      enzymatic digests using UV detection with or without mass spectrometric
      detection. The quantitation of oxidation is performed based on the UV or
      extracted ion chromatographic peak areas of the oxidized and non-oxidized
      peptides. This method was found to be susceptible to significant variability over
      long-term use. Major factors leading to this variability included presence of low
      levels of metal ions, especially iron, in the digestion buffer, chromatographic
      column, LC injector, and other sample contact surfaces. Careful control of metal
      ion levels generally leads to less variability and long-term consistency of
      peptide mapping methods for oxidation determination.

PMID- 22483986
TI  - The layout of a bacterial genome.
AB  - Recently the mismatch between our newly acquired capacity to synthetize DNA at
      genome scale, and our low capacity to design ab initio a functional genome has
      become conspicuous. This essay gathers a variety of constraints that globally
      shape natural genomes, with a focus on eubacteria. These constraints originate
      from chromosome replication (leading/lagging strand asymmetry; gene dosage
      gradient from origin to terminus; collisions with the transcription complexes),
      from biased codon usage, from noise control in gene expression, and from genome
      layout for co-functional genes. On the basis of this analysis, lessons are drawn
      for full genome design.

PMID- 22483987
TI  - SUMOylation of the kainate receptor subunit GluK2 contributes to the activation
      of the MLK3-JNK3 pathway following kainate stimulation.
AB  - Protein SUMOylation has been implicated in the pathogenesis of ischemic stroke.
      However, the underlying mechanisms remain unclear. Here, we found that global
      brain ischemia evokes a sustained elevation of GluK2 SUMOylation in the rat
      hippocampal CA1 region. Over-expression of wild-type GluK2, but not SUMOylation
      deficient mutant, significantly increased the activity of MLK3 and JNK3 after
      kainate stimulation. SUMOylation deficiency attenuated the kainate-stimulated
      interaction between MLK3 and GluK2. In addition, inhibition of kainate-evoked
      GluK2 endocytosis decreased the activation of MLK3-JNK3 signaling and the binding
      of MLK3-GluK2 in cultured cortical neurons. These results suggest that the
      internalization of GluK2 following SUMO modification promotes its binding with
      MLK3, thereby activating the MLK3-JNK3 pathway, which may be responsible for
      ischemic neuronal cell death.

PMID- 22483988
TI  - PIWIL4 regulates cervical cancer cell line growth and is involved in down
      regulating the expression of p14ARF and p53.
AB  - Recently, PIWIL4 has been identified as a functional protein involved in
      tumorigenesis. Cervical cancer is the second most prevalent form of cancer
      worldwide. The relationship between PIWIL4 and cervical cancer is still unknown.
      Here, we found that PIWIL4 is up-regulated in human cervical cancer tissues in
      comparison to adjacent normal tissues, and it promotes cell growth and
      proliferation by inhibiting apoptosis through the p14ARF/p53 pathway. PIWIL4 can
      also promote the invasion of cervical cancer cells. These results suggest that
      PIWIL4 might play an oncogenic role in cervical cancer and be useful as a new
      therapeutic target in the future.

PMID- 22483989
TI  - Reconstruct large osteochondral defects of the knee with hIGF-1 gene enhanced
      Mosaicplasty.
AB  - OBJECTIVE: To investigate a compound technique including gene therapy, injectable
      tissue engineering and Mosaicplasty to reconstruct large osteochondral defect.
      METHODS: Plasmid vector containing hIGF-1 cDNA was created and transfected into
      BMSCs in vitro with FuGene6. After gene expression determination, cells were
      mixed with calcium alginate gel. Osteochondral defects were created on the
      femoral condyle of goats in a diameter of 6mm. Osteochondral plugs were harvested
      from the intertrochlea groove and pressed into the recipient sites in a mosaic
      mode. Gene modified BMSCs-scaffold complex was applied to fill the residual
      defects. Control groups were also set up. At 4 and 16 weeks, specimens were
      investigated in gross and under microscopy, electromicroscopy and MRI detection.
      RESULTS: hIGF-I gene was expressed effectively with the peak concentration at
      34.75 ng/ml. Subchondral bone and cartilage were integrated well in gene enhanced
      Mosaicplasty group. The reconstructed tissue filled up the gaps between columns,
      which appeared better than other groups. The regenerated cartilage was integrated
      with neighbor tightly in regular arrange. Extracellular matrix distributed evenly
      and deeply stained by alcian blue. Quantitative histologic assessments showed
      higher score in gene enhanced Mosaicplasty group. Glycosaminoglycan assay
      revealed no difference between groups involving Mosaicplasty. MRI analysis
      demonstrated the healing process between the subchondral bone other than control
      groups. CONCLUSIONS: hIGF-I gene enhanced tissue engineering can modify the
      outcome of Mosaicplasty to reconstruct large osteochondral defects in weight
      bearing region.

PMID- 22483990
TI  - An overview of values for the threshold of toxicological concern.
AB  - An overview of values for the threshold of toxicological concern (TTC) is
      presented. This comprises the more established TTC values, including those that
      have been endorsed by regulatory bodies, and those that have more recently been
      proposed and may still need further development. The overview is structured by
      use/exposure scenario and provides, in particular, key information on the
      underlying databases. It is aimed to support the application of the TTC approach
      in the risk assessment of chemicals whereby it is important to be aware under
      which circumstances a certain TTC value can be applied. Some recommendations for
      potential future developments to further improve the TTC approach are also being
      made.

PMID- 22483991
TI  - Erbium:YAG laser resurfacing increases skin permeability and the risk of
      excessive absorption of antibiotics and sunscreens: the influence of skin
      recovery on drug absorption.
AB  - While laser skin resurfacing is expected to result in reduced barrier function
      and increased risk of drug absorption, the extent of the increment has not yet
      been systematically investigated. We aimed to establish the skin permeation
      profiles of tetracycline and sunscreens after exposure to the erbium:yttrium
      aluminum-garnet (Er:YAG) laser during postoperative periods. Physiological and
      histopathological examinations were carried out for 5 days after laser treatment
      on nude mice. Percutaneous absorption of the permeants was determined by an in
      vitro Franz cell. Ablation depths varied in reaching the stratum corneum (10 MUm,
      2.5 J/cm2) to approach the epidermis (25 MUm, 6.25 J/cm2) and upper dermis (40
      MUm, 10 J/cm2). Reepithelialization evaluated by transepidermal water loss was
      complete within 2-4 days and depended on the ablation depth. Epidermal
      hyperplasia was observed in the 40-MUm-treated group. The laser was sufficient to
      disrupt the skin barrier and allow the transport of the permeants into and across
      the skin. The laser fluence was found to play an important role in modulating
      skin absorption. A 25-MUm ablation depth increased tetracycline flux 84-fold. A
      much smaller enhancement (3.3-fold) was detected for tetracycline accumulation
      within the skin. The laser with different fluences produced enhancement of
      oxybenzone skin deposition of 3.4-6.4-fold relative to the untreated group. No
      penetration across the skin was shown regardless of whether titanium dioxide was
      applied to intact or laser-treated skin. However, laser resurfacing increased the
      skin deposition of titanium dioxide from 46 to 109-188 ng/g. Tetracycline
      absorption had recovered to the level of intact skin after 5 days, while more
      time was required for oxybenzone absorption. The in vivo skin accumulation and
      plasma concentration revealed that the laser could increase tetracycline
      absorption 2-3-fold. The experimental results indicated that clinicians should be
      cautious when determining the dose for postoperative treatment.

PMID- 22483992
TI  - Immunopathological effects of experimental T-2 mycotoxocosis in broiler chicken
      co-infected with infectious bronchitis virus (IBV).
AB  - A total of 128 1-week-old chicks were classified into four groups; T-2 toxin fed
      (T-2), IBV infected (IBV), T-2 toxin fed and co-infected with IBV (T-2+IBV), and
      untreated (control) for a period of 6 weeks. Within their respective groups, the
      birds belonged to T-2 and T-2+IBV were exposed to 2 ppm of T-2 toxin contaminated
      feed for 6 weeks, and 0.2 ml of 10 EID(50) (10(5.69)/0.2 ml) inoculums of IBV
      isolate (India/LKW/56/IVRI/08) was used to challenge the chicks belonged to IBV
      alone and T-2+IBV groups after 3 weeks of the experiment. To study
      immunopathological effects, parameters such as lymphocyte stimulation indices
      (SI), haemagglutination inhibition, enzyme linked immunosorbant assay (ELISA),
      peripheral lymphocytes CD(4)(+) and CD(8)(+) analysis, and histopathological
      examination of lymphoid organs were done. Accordingly, SI values were
      significantly (P<0.05) lower in all the treatment groups as compared to control,
      however, the SI values of IBV infected group were significantly higher than the
      values in toxin fed groups. The mean HI titres to ND vaccine was significantly
      (P<0.05) lower in the toxin groups at all the intervals, and the antibody titres
      in IBV infected group were significantly (P<0.05) higher than that of T-2 toxin
      fed and co-infected with IBV group but were significantly (P<0.05) lower than the
      control at 21 (3) and 28 (10) days of toxin feeding (DTF) (days post infection
      (DPI)). Similarly, the mean IBV ELISA antibody titres in the toxin fed groups
      were significantly (P<0.01) reduced as compared with the IBV ELISA antibody
      titres of IBV infected but not toxin fed group, at all intervals. Peripheral
      CD(4)(+):CD(8)(+) ratios in T-2+IBV group and number of CD(4)(+) and CD(8)(+)
      peripheral lymphocytes in all treatment groups were significantly reduced as
      compared to the values in control birds. However, CD(4)(+):CD(8)(+) ratios of IBV
      infected group at 42 (21) DTF (DPI) were found significantly (P<0.05) higher than
      the values in control birds. Histopathologically, lymphoid organs (bursa of
      Fabricius, spleen, thymus, caecal tonsils and Harderian glands) showed moderate
      to severe necrosis (lymphocytolysis) and extensive lymphocyte depletion in all
      the toxin groups (T-2 and T-2+IBV groups) where the severity and extent of the
      lesions were more in T-2+IBV group. The findings of the present experiment
      revealed immunosuppressive effects of T-2 toxin and aggravated the pathology and
      pathogenesis of IBV infection.

PMID- 22483993
TI  - Condensed tannins from Botswanan forage plants are effective priming agents of
      gammadelta T cells in ruminants.
AB  - The potential impact of extracts from forage plants on gammadelta T cell activity
      in ruminants was evaluated using an in vitro immunoassay. This study investigated
      whether plant extracts could prime gammadelta T cells via up-regulation of CD25
      (interleukin-2 receptor alpha). Purified Sephadex LH-20 fractions, isolated from
      Viscum rotundifolium, Viscum verrucosum, Tapinanthus oleifolius and Grewia flava,
      were screened against gammadelta T cells on kid, lamb and calf peripheral blood
      lymphocytes. Condensed tannins (CT) from G. flava significantly primed gammadelta
      T cells in kids up to 64.75% at 10 MUg/mL, which was statistically significant
      relative to the negative control at 22.66% (p=0.004). CT from T. oleifolius also
      induced priming of gammadelta T cells in kids, while fractions from V.
      rotundifolium and V. verrucosum induced minimal priming of gammadelta T cells. In
      contrast, there was no significant priming of gammadelta T cells from lambs and
      calves for any of the tested fractions (p>0.05). These findings suggest that CT
      from a selected range of Botswanan forage plants can stimulate the immune system
      in vivo in selected ruminant species and may participate in enhancing host innate
      immune responses.

PMID- 22483994
TI  - Systematic review and meta-analysis of randomized controlled trials on topical
      interventions for genital lichen sclerosus.
AB  - BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory dermatosis that
      occurs mainly in the anogenital area and causes itching and soreness. Progressive
      destructive scarring may result in burying of the clitoris in females and
      phimosis in males. Affected people have an increased risk of genital cancers.
      OBJECTIVE: We sought to assess the effects of topical interventions for genital
      LS. METHODS: We undertook a systematic review and meta-analysis using the
      methodology of the Cochrane Collaboration. RESULTS: We included 7 randomized
      controlled trials with a total of 249 participants covering 6 treatments.
      Clobetasol propionate 0.05% was better than placebo in treating genital LS
      (participant-rated improvement/remission of symptoms: risk ratio 2.85 [95%
      confidence interval {CI} 1.45-5.61]; investigator-rated global degree of
      improvement: standardized mean difference [SMD] 5.74 [95% CI 4.26-7.23]) as was
      mometasone furoate 0.05% (change in clinical grade of phimosis: SMD -1.04 [95% CI
      -1.77 to -0.31]). We found no evidence supporting the efficacy of topical
      androgens and progesterone. There were no differences between pimecrolimus and
      clobetasol propionate in relieving symptoms through change in pruritus (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 in improving
      gross appearance (investigator-rated global degree of improvement: SMD -1.64 [95%
      CI -2.40 to -0.87]). LIMITATIONS: Most of the included studies were small.
      CONCLUSIONS: The current limited evidence supports the efficacy of clobetasol
      propionate, mometasone furoate, and pimecrolimus in treating genital LS. Further
      randomized controlled trials are needed.

PMID- 22483995
TI  - Global trauma registry mapping: a scoping review.
AB  - BACKGROUND: The burden of injury is very high in developing countries. Trauma
      systems reduce mortality; the trauma registry is a key driver of improvements in
      trauma care. Developing countries have begun to develop trauma systems but the
      level of local trauma registry activity is unclear. The aim of this study was to
      determine a global estimate of trauma registry activity. METHODS: A structured
      review of the literature was performed. All abstracts referring to a trauma
      registry over a two-year period were included. For the trauma registry described
      in each abstract, the source country was recorded. An additional search of web
      pages posted over a one year period was conducted. Those linked to an active
      trauma registry website were included and the country of the trauma registry was
      recorded. A selection of trauma registries from countries of different levels of
      development were identified and compared. RESULTS: 571 abstracts were included in
      the review. Most articles utilised "general" trauma registries (436(76%)) and
      were based at a single hospital (279(49%)). Other registries were limited to
      military or paediatric populations (36(6%) and 35(6%) articles respectively).
      Most articles sourced registries from the US (288(50%)), followed by Australia
      (45(8%)), Germany (32(6%)), Canada (27(5%)), UK (13(2%)), China (13(2%)) and
      Israel (12(2%)). The Americas produced most trauma registry articles and South
      East Asia the least. The majority of trauma registry articles originated from
      very highly developed countries 467(82%). Least developed countries had the
      fewest (5(1%)). The additional search yielded 37 web pages linked to 27 different
      trauma registry websites. Most of these were based in the US (16(59%)). The basic
      features of trauma registries, such as inclusion criteria, number and type of
      variables and injury severity scoring, varied widely depending on the country's
      level of development. CONCLUSION: This review, using a combination of the number
      of trauma registry articles and web pages to locate active trauma registries,
      demonstrated the disparity in trauma registry activity between the most and least
      developed countries. The absence of trauma care information systems remains a
      challenge to trauma system development globally.

PMID- 22483996
TI  - Detecting outlier peptides in quantitative high-throughput mass spectrometry
      data.
AB  - Quantitative high-throughput mass spectrometry has become an established tool to
      measure relative gene expression proteome-wide. The output of such an experiment
      usually consists of a list of expression ratios (fold changes) for several
      thousand proteins between two conditions. However, we observed that individual
      peptide fold changes may show a significantly different behavior than other
      peptides from the same protein and that these differences cannot be explained by
      imprecise measurements. Such outlier peptides can be the consequence of several
      technical (misidentifications, misquantifications) or biological (post
      translational modifications, differential regulation of isoforms) reasons. We
      developed a method to detect outlier peptides in mass spectrometry data which is
      able to delineate imprecise measurements from real outlier peptides with high
      accuracy when the true difference is as small as 1.4 fold. We applied our method
      to experimental data and investigated the different technical and biological
      effects that result in outlier peptides. Our method will assist future research
      to reduce technical bias and can help to identify genes with differentially
      regulated protein isoforms in high throughput mass spectrometry data.

PMID- 22483997
TI  - Identification of a potential biomarker panel for the intake of the common
      dietary trans fat elaidic acid (trans?9-C18:1).
AB  - Trans fatty acid intake has been correlated to an unfavorable plasma lipoprotein
      profile and an increased cardiovascular disease risk. The present study aimed to
      identify a plasma protein biomarker panel related to human intake of elaidic
      acid. The human liver cell line HepG2-SF was used as a model system, and the
      cells were maintained for seven days in serum-free medium containing 100 MUM
      elaidic acid (trans?9-C18:1), oleic acid (cis?9-C18:1) or stearic acid (C18:0).
      The secretomes were analyzed by stable isotope labeling of amino acids in cell
      culture (SILAC), difference in gel electrophoresis (DIGE) and gene expression
      microarray analysis. Twelve proteins were found to be differentially regulated
      based on SILAC data (>1.3 fold change, P-value<0.05), 13 proteins were found to
      be differentially regulated based on DIGE analysis (>1.3 fold change, P
      value<0.05), and 17 mRNA transcripts encoding extracellular proteins were
      determined to be affected (>1.3 fold change, P-value<0.01) following the addition
      of elaidic acid compared to oleic acid or stearic acid. The results revealed that
      37 proteins were regulated specifically in response to elaidic acid exposure, and
      nine of these proteins were confirmed to be regulated in this manner by using
      selected reaction monitoring mass spectrometry.

PMID- 22483998
TI  - GABAergic processes within the median preoptic nucleus promote NREM sleep.
AB  - GABAergic mechanisms in the preoptic region of the hypothalamus (POA) have been
      implicated in the generation and maintenance of NREM (quiet) sleep. We recently
      reported that neurons in the median peptic nucleus (MnPN) in the POA of the cat
      are selectively activated during NREM sleep. In the present study, we explored
      the hypothesis that NREM sleep is controlled by GABAergic mechanisms within the
      MnPN. Consequently, adult cats were utilized to determine GABA immunorreactivity
      within the MnPN and to examine the effects on sleep of the microinjection of a
      GABA(A) agonist (muscimol) and a GABA(A) antagonist (bicuculline) into this area.
      GABAergic neurons were present throughout the MnPN. Compared with control
      microinjections, after the application of muscimol, the time spent in NREM sleep
      (59.8+/-7.5 min) and REM sleep (6.9+/-4.7 min) decreased compared with control
      microinjections (103.8+/-5.2 and 20.2+/-4.3 min, respectively; P<0.005). In
      contrast, bicuculline microinjections increased only NREM sleep time (103.0+/
      23.0 vs 77.7+/-23.7 min; P<0.05). These results demonstrate that GABAergic
      processes within the MnPN are involved in the generation and maintenance of
      sleep, especially NREM sleep.

PMID- 22483999
TI  - The evolution of plant pathogens in response to host resistance: factors
      affecting the gain from deployment of qualitative and quantitative resistance.
AB  - Disease resistance genes are valuable natural resources which should be deployed
      in a way which maximises the gain to crop productivity before they lose efficacy.
      Here we present a general epidemiological model for plant diseases, formulated to
      study the evolution of phenotypic traits of plant pathogens in response to host
      resistance. The model was used to analyse how the characteristics of the disease
      resistance, and the method of deployment, affect the size and duration of the
      gain. The gain obtained from growing a resistant cultivar, compared to a
      susceptible cultivar, was quantified as the increase in green canopy area
      resulting from control of foliar disease, integrated over many years-termed
      'Healthy Area Duration (HAD) Gain'. Previous work has suggested that the effect
      of crop ratio (the proportion of land area occupied by the resistant crop) on the
      gain from qualitative (gene-for-gene) resistance is negligible. Increasing the
      crop ratio increases the area of uninfected host, but the resistance is more
      rapidly broken; these two effects counteract each other. We tested the hypothesis
      that similar counteracting effects would occur for quantitative, multi-genic
      resistance, but found that the HAD Gain increased at higher crop ratios. Then we
      tested the hypothesis that the gain from quantitative host resistance could
      differ depending on the life-cycle component (sporulation rate or infection
      efficiency) constrained by the resistance. For the patho-system considered, a
      quantitative resistant cultivar that reduced the infection efficiency gave a
      greater HAD Gain than a cultivar that reduced sporulation rate, despite having
      equivalent transmission rates.

PMID- 22484000
TI  - Comment on "Ecological importance of the thermal emissivity of avian eggshells".
AB  - Eggshell emissivity must be known to determine accurately the cooling rate of
      avian eggs when the parent, after heating by conduction during the incubation, is
      temporarily absent. We estimate possible values of eggshell emissivities from in
      situ measurements and spectral libraries. Emissivity is near to 1 (probably
      higher than 0.95) and therefore its effect on cooling rate may be negligible,
      with differences between the temperature of the egg assuming a value of
      epsilon=0.95 and that of a blackbody (epsilon=1) below 0.2  degrees C.

PMID- 22484001
TI  - Prenatal nicotine exposure alters the response of the mouse in vitro respiratory
      rhythm to hypoxia.
AB  - Prenatal nicotine exposure is associated with deficiencies in the ability to
      respond to life threatening stressors such as hypoxia. Although many of these
      deficiencies appear to originate from defects in the brainstem respiratory
      network, the specific effects of prenatal nicotine exposure on the brainstem
      respiratory network are not well understood. We have tested the effects of
      prenatal nicotine exposure on the respiratory rhythm using an in vitro mouse
      brainstem slice preparation containing the pre-Botzinger Complex, a region of the
      ventral respiratory group that is the postulated site of inspiratory rhythm
      generation. We found that nicotine exposure during pre- and early postnatal
      development led to a lower frequency of baseline fictive respiratory discharges
      from rhythmic slices and a reduction in the ability of the slice to maintain a
      respiratory rhythm during exposure to severe hypoxia compared to controls. These
      impairments of the central respiratory rhythm could potentially affect the
      ability to survive a period of exposure to severe hypoxia in vivo.

PMID- 22484002
TI  - On- and off-exercise kinetics of cardiac output in response to cycling and
      walking in COPD patients with GOLD Stages I-IV.
AB  - Exercise-induced dynamic hyperinflation and large intrathoracic pressure swings
      may compromise the normal increase in cardiac output (Q) in Chronic Obstructive
      Pulmonary Disease (COPD). Therefore, it is anticipated that the greater the
      disease severity, the greater would be the impairment in cardiac output during
      exercise. Eighty COPD patients (20 at each GOLD Stage) and 10 healthy age-matched
      individuals undertook a constant-load test on a cycle-ergometer (75% WR(peak))
      and a 6min walking test (6MWT). Cardiac output was measured by bioimpedance
      (PhysioFlow, Enduro) to determine the mean response time at the onset of exercise
      (MRTon) and during recovery (MRToff). Whilst cardiac output mean response time
      was not different between the two exercise protocols, MRT responses during
      cycling were slower in GOLD Stages III and IV compared to Stages I and II (MRTon:
      Stage I: 45+/-2, Stage II: 65+/-3, Stage III: 90+/-3, Stage IV: 106+/-3s; MRToff:
      Stage I: 42+/-2, Stage II: 68+/-3, Stage III: 87+/-3, Stage IV: 104+/-3s,
      respectively). In conclusion, the more advanced the disease severity the more
      impaired is the hemodynamic response to constant-load exercise and the 6MWT,
      possibly reflecting greater cardiovascular impairment and/or greater physical
      deconditioning.

PMID- 22484003
TI  - Cognitive performance is impaired in coeliac patients on gluten free diet: a case
      control study in patients older than 65 years of age.
AB  - INTRODUCTION: Retrospective studies and case reports suggest an association
      between coeliac disease and impaired cognitive function. AIM: To evaluate
      functional and cognitive performances in coeliac disease vs. control patients
      older than 65 years. METHOD: Eighteen coeliac disease patients (75+/-4 years,
      group A) on gluten free diet since 5.5+/-3 years and 18 age-sex matched controls
      (76+/-4 years, group B) were studied using a battery of neuropsychological tests.
      Results of functional and cognitive tests are expressed as "row scores" and as
      "equivalent scores" by relating "raw scores" to reference rank categories.
      RESULTS: Barthel Index of functional performance was similar in the 2 groups.
      "Raw score" was significantly lower in coeliac disease than controls for Mini
      Mental Test Examination (p=0.02), Trail Making Test (p=0.001), Semantic Fluency
      (p=0.03), Digit Symbol Test (p=0.007), Ideo-motor apraxia (p<0.001) and Bucco
      facial apraxia (p<0.002). "Equivalent score" was also lower in coeliac disease
      than controls for Semantic memory (p<0.01) and for Ideo-motor apraxia (p=0.007).
      CONCLUSION: Cognitive performance is worse in elderly coeliac disease than
      control patients, despite prolonged gluten avoidance in coeliacs. Awareness on
      the increasing phenomenon of late-onset coeliac disease is important to minimize
      diagnostic delay and prolonged exposure to gluten that may adversely and
      irreversibly affect cognitive function.

PMID- 22484004
TI  - Efficacy of 20-OH-ecdysone on hepatic key enzymes of carbohydrate metabolism in
      streptozotocin induced diabetic rats.
AB  - The aim of the present investigation was to evaluate the anti-diabetic activity
      of 20-OH-ecdysone on glucose metabolic key enzymes in control and streptozotocin
      induced diabetic rats. On oral administration of 20-OH-ecdysone at a dose of
      5mg/kg body weight per day to diabetic rats for 30 days resulted in a significant
      decrease in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and an
      increase in the levels of insulin and hemoglobin. Administration of 20-OH
      ecdysone showed significant increase in the levels of glycolytic enzyme
      (hexokinase) and hepatic shunt enzyme (glucose-6-phosphate dehydrogenase) whereas
      significant decrease in the levels of gluconeogenic enzymes (glucose-6
      phosphatase and fructose-1,6-bisphosphatase) in diabetic treated rats.
      Furthermore, protection against body weight loss of diabetic animals also
      observed. This study indicates that the administration of 20-OH-ecdysone to
      diabetic rats resulted in alterations in the metabolism of glucose with
      subsequent reduction in plasma glucose levels. A comparison was made between the
      action of 20-OH-ecdysone and antidiabetic drug-glibenclamide. The effects
      produced by the 20-OH-ecdysone were comparable to that of glibenclamide.

PMID- 22484005
TI  - Impact of eating disorders and psychological distress on the quality of life of
      obese people.
AB  - OBJECTIVE: Quality of life (QoL) is impaired in obesity, but the roles of eating
      behavior and psychological distress need to be more documented. METHODS: One
      hundred thirty consecutive obese patients seeking medical care filled out
      questionnaires evaluating QoL, the presence of an eating disorder (ED), levels of
      anxiety and depression, and perception of body image. RESULTS: Global QoL was
      poor in 16.4% and intermediate in 61.8% of the patients. EDs were present in 58%
      of patients who were more (P = 0.05) overweight; 24.2% of patients had binging.
      EDs impaired significantly the global and specific dimensions of QoL; binging
      impaired physical and sexual QoLs (both P < 0.02). Anxiety and depression were
      found in 73.6% and 50.4% of patients, respectively; depression was more frequent
      in women (P = 0.007) and in patients with EDs. Anxiety and/or depression impaired
      global (P < 0.001) and specific dimensions of QoL. Body shape concern was marked
      in 86.4% of women and associated with poor global (P < 0.001) and specific QoL,
      and with anxiety and depression. CONCLUSION: The impairment of QoL in obese
      patients is increased by the presence of an ED, anxiety, and/or depression and
      marked body shape concern. These psychological factors should be assessed more
      carefully and taken into account in global strategies aiming to improve the well
      being of obese patients.

PMID- 22484006
TI  - Dietary glycemic index and glycemic load among Indigenous and non-Indigenous
      children aged 10-12 years.
AB  - OBJECTIVE: This study aimed to estimate the dietary glycemic index (GI) and
      glycemic load (GL) of Australian Aboriginal and Torres Strait Islander and non
      Indigenous rural children and identify the main foods contributing to their GI
      and GL. METHODS: A cross-sectional analysis of food intake of 215 children (38.1%
      were Aboriginal and Torres Strait Islanders) 10 to 12 y old obtained by three 24
      h recalls was conducted. The foods were ranked according to their total
      contribution to total carbohydrates, GI, and GL. RESULTS: Aboriginal and Torres
      Strait Islander participants had a significantly higher dietary GL (155.8 +/-
      46.8 versus 135.4 +/- 31.2, P < 0.001) and GI (58.3 +/- 3.9 versus 56.9 +/- 3.8,
      P = 0.008) than the non-Indigenous participants. White breads were the main
      contributors of GI and GL in both groups and were a main driver for the
      increasing GI. Fiber was not associated with GI, whereas sugar and starch were
      positively associated. Subjects with a higher GI tended to be less physically
      active. CONCLUSION: The quality of carbohydrates in the diets of the participants
      was low, with poorer dietary items contributing most of the GI and GL.
      Substituting white breads with low/lower GI alternatives may be a useful
      strategy.

PMID- 22484007
TI  - Disubstituted 1,8-dipyrazolcarbazole derivatives as a new type of c-myc G
      quadruplex binding ligands.
AB  - A series of 1,8-dipyrazolcarbazole (DPC) derivatives (6a-6d, 7a-7d) designed as G
      quadruplex ligands have been synthesized and characterized. The FRET-melting and
      SPR results showed that the DPC derivatives could well recognize G-quadruplex
      with strong discrimination against the duplex DNA. In addition, the DPC
      derivatives showed much stronger stabilization activities and binding affinities
      for c-myc G-quadruplex rather than telomeric G-quadruplex. Therefore, their
      interactions with c-myc G-quadruplex were further explored by means of CD
      spectroscopy, PCR-stop assay, and molecular modeling. In cellular studies, all
      compounds showed strong cytotoxicity against cancer cells, while weak
      cytotoxicity towards normal cells. RT-PCR assay showed that compound 7b could
      down-regulate c-myc gene expression in Ramos cell line, while had no effect on c
      myc expression in CA46 cell line with NHE III(1) element removed, indicating its
      effective binding with G-quadruplex on c-myc oncogene in vivo.

PMID- 22484008
TI  - Combining multiple classifications of chemical structures using consensus
      clustering.
AB  - Consensus clustering involves combining multiple clusterings of the same set of
      objects to achieve a single clustering that will, hopefully, provide a better
      picture of the groupings that are present in a dataset. This Letter reports the
      use of consensus clustering methods on sets of chemical compounds represented by
      2D fingerprints. Experiments with DUD, IDAlert, MDDR and MUV data suggests that
      consensus methods are unlikely to result in significant improvements in
      clustering effectiveness as compared to the use of a single clustering method.

PMID- 22484010
TI  - Dirty utility room design and aerosolization of organisms.

PMID- 22484009
TI  - Growth hormone secretagogue receptor (GHS-R1a) knockout mice exhibit improved
      spatial memory and deficits in contextual memory.
AB  - Although the hormone ghrelin is best known for its stimulatory effect on appetite
      and regulation of growth hormone release, it is also reported to have beneficial
      effects on learning and memory formation in mice. Nevertheless, controversy
      exists about whether endogenous ghrelin acts on its receptors in extra
      hypothalamic areas of the brain. The ghrelin receptor (GHS-R1a) is co-expressed
      in neurons that express dopamine receptor type-1 (DRD1a) and type-2 (DRD2), and
      we have shown that a subset of GHS-R1a, which are not occupied by the agonist
      (apo-GHSR1a), heterodimerize with these two receptors to regulate dopamine
      signaling in vitro and in vivo. To determine the consequences of ghsr ablation on
      brain function, congenic ghsr -/- mice on the C57BL6/J background were subjected
      to a battery of behavioral tests. We show that the ghsr -/- mice exhibit normal
      balance, movement, coordination, and pain sensation, outperform ghsr +/+ mice in
      the Morris water maze, but show deficits in contextual fear conditioning.

PMID- 22484011
TI  - Working memory capacity affects the interference control of distractors at
      auditory gating.
AB  - It is important to understand the role of individual differences in working
      memory capacity (WMC). We investigated the relation between differences in WMC
      and N1 in event-related brain potentials as a measure of early selective
      attention for an auditory distractor in three-stimulus oddball tasks that
      required minimum memory. A high-WMC group (n=13) showed a smaller N1 in response
      to a distractor and target than did a low-WMC group (n=13) in the novel condition
      with high distraction. However, in the simple condition with low distraction,
      there was no difference in N1 between the groups. For all participants (n=52),
      the correlation between the scores for WMC and N1 peak amplitude was strong for
      distractors in the novel condition, whereas there was no relation in the simple
      condition. These results suggest that WMC can predict the interference control
      for a salient distractor at auditory gating even during a selective attention
      task.

PMID- 22484012
TI  - Prefrontal brain asymmetry and aggression in imprisoned violent offenders.
AB  - Anterior brain asymmetry, assessed through the alpha and beta band in resting
      state electroencephalogram (EEG) is associated with approach-related behavioral
      dispositions, particularly with aggression in the general population. To date,
      the association between frontal asymmetry and aggression has not been examined in
      highly aggressive groups. We examined the topographic characteristics of alpha
      and beta activity, the relation of both asymmetry metrics to trait aggression,
      and whether alpha asymmetry was extreme in anterior regions according to clinical
      standards in a group of imprisoned violent offenders. As expected, these
      individuals were characterized by stronger right than left-hemispheric alpha
      activity, which was putatively extreme in anterior regions in one third of the
      cases. We also report that in line with observations made in the general
      population, aggression was associated with stronger right-frontal alpha activity
      in these violent individuals. This suggests that frontal alpha asymmetry, as a
      correlate of trait aggression, might be utilizable as an outcome measure in
      studies which assess the effects of anti-aggressiveness training in violent
      offenders.

PMID- 22484013
TI  - Experimental simulation of the effects of sudden increases in geomagnetic
      activity upon quantitative measures of human brain activity: validation of
      correlational studies.
AB  - Previous correlations between geomagnetic activity and quantitative changes in
      electroencephalographic power revealed particular associations with the right
      parietal lobe for theta activity and the right frontal region for gamma activity.
      In the present experiment subjects were exposed to either no field (sham
      conditions) or to either 20 nT or 70 nT, 7 Hz, amplitude modulated (mHz range)
      magnetic fields for 30 min. Quantitative electroencephalographic (QEEG)
      measurements were completed before, during, and after the field exposures. After
      about 10 min of exposure theta power over the right parietal region was enhanced
      for the 20 nT exposure but suppressed for the 70 nT exposure relative to sham
      field exposures. The effect dissipated by the end of the exposure. These results
      support the contention that magnetic field fluctuations were primarily
      responsible for the significant geomagnetic-QEEG correlations reported in several
      studies.

PMID- 22484014
TI  - Levetiracetam inhibits neurotransmitter release associated with CICR.
AB  - To define the antiepileptic mechanisms of levetiracetam (LEV), the present study
      determined the concentration-dependent effects of locally perfused LEV on the
      releases of norepinephrine, dopamine, serotonin, l-glutamate and GABA induced by
      50 mMK(+)-evoked stimulation and agonists of ryanodine receptor (RyR) and
      inositol-triphosphate receptor (IP3R) in the median prefrontal cortex (mPFC)
      using in vivo microdialysis. Local perfusion with LEV (10, 30 and 100 MUM) alone
      did not affect the extracellular levels of all neurotransmitters in the mPFC. The
      release of neurotransmitters induced by K(+)-evoked stimulation was inhibited by
      perfusion with LEV in a concentration-dependent manner, and those induced by
      agonists of RyR and IP3R were also inhibited by LEV. Specifically, the RyR
      induced release was inhibited by 10 MUM LEV, whereas the IP3R-induced release was
      inhibited by 100 MUM LEV, but not by 10 or 30 MUM LEV. The above results suggest
      that LEV has little effect on the components of normal synaptic transmission but
      selectively inhibits transmission induced by neuronal hyperactivation. Thus, the
      mechanisms of the antiepileptic and neuroprotective actions of LEV seem to be
      mediated, at least in part, through the combination of these two inhibitory
      effects on depolarization-induced and CICR-associated neurotransmitter releases.

PMID- 22484015
TI  - Repeated paired-testing impairs extinction of morphine-induced conditioned place
      preference dependent on the inter-test interval in rats.
AB  - Using exposure to morphine- and saline-paired sides alternatively as the
      extinction training procedure, we find that post-retrieval extinction training
      enhances or hinders the extinction of morphine-induced conditioned place
      preference (CPP) dependent on the retrieval-extinction training intervals. Here,
      we examine the influence of post-retrieval extinction training with repeated
      paired testing on extinction of morphine-induced CPP of rats. Our results
      demonstrate that paired-testing with a 10-min inter-test interval does not
      influence the extinction of CPP, while post-retrieval extinction training blocks
      the extinction of CPP with a 3-h retrieval-extinction interval. These results
      strongly indicate that the interval between exposure trials influences the
      outcome of exposure therapy in addiction treatment.

PMID- 22484016
TI  - The nature of the homophone density effect: an ERP study with Chinese spoken
      monosyllable homophones.
AB  - For spoken Chinese, there is an abundance of homophones. For example, the number
      of homophone mates ranges from 2 to 48 for about 75% Chinese monosyllables. The
      present study investigated the effect of homophone density using an auditory
      lexical decision task. In Experiment 1, participants responded more slowly to
      monosyllabic homophones with more homophone mates than those with fewer mates,
      showing a clear inhibitory homophone density effect. To understand whether this
      inhibitory effect could be attributed to the competition among multiple
      orthographic/semantic codes associated with a homophone, Experiment 2 examined
      neural correlates of the homophone density effect with event-related potentials
      (ERPs). Results suggest that ERP effects in the 600-800 ms time window
      correlating with homophone density reflects competition among a homophone's
      multiple semantic meanings as opposed to its multiple spellings.

PMID- 22484017
TI  - Acute neuroprotective effects of extremely low-frequency electromagnetic fields
      after traumatic brain injury in rats.
AB  - Traumatic brain injury commonly has a result of a short window of opportunity
      between the period of initial brain injury and secondary brain injury, which
      provides protective strategies and can reduce damages of brain due to secondary
      brain injury. Previous studies have reported neuroprotective effects of extremely
      low-frequency electromagnetic fields. However, the effects of extremely low
      frequency electromagnetic fields on neural damage after traumatic brain injury
      have not been reported yet. The present study aims to investigate effects of
      extremely low-frequency electromagnetic fields on neuroprotection after traumatic
      brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid
      percussion injury, which were placed in non-electromagnetic fields and 15 Hz
      (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At
      various time points (ranging from 0.5 to 30 h) after lateral fluid percussion
      injury, rats were treated with kainic acid (administered by intraperitoneal
      injection) to induce apoptosis in hippocampal cells. The results were as follows:
      (1) the expression of hypoxia-inducible factor-1alpha was dramatically decreased
      during the neuroprotective time window. (2) The kainic acid-induced apoptosis in
      the hippocampus was significantly decreased in rats exposed to electromagnetic
      fields. (3) Electromagnetic fields exposure shortened the escape time in water
      maze test. (4) Electromagnetic fields exposure accelerated the recovery of the
      blood-brain barrier after brain injury. These findings revealed that extremely
      low-frequency electromagnetic fields significantly prolong the window of
      opportunity for brain protection and enhance the intensity of neuroprotection
      after traumatic brain injury.

PMID- 22484019
TI  - The relationship of testosterone and AR CAG repeat genotype with knee extensor
      muscle function of young and older men.
AB  - The inter-relationship between muscle strength and serum testosterone is not
      fully understood, and may be confounded or influenced by age. The polymorphism of
      androgen receptor gene CAG number (AR CAGn) could also influence these variables.
      The study examined the relationship between total testosterone (TT), free
      testosterone (FT) and AR CAGn with the muscle strength of young (YM, 18-30 yrs,
      n=82) and older (OM, 60-70 yrs, n=101) Caucasian men. Knee extensor strength was
      measured isometrically and isokinetically, and thigh and whole-body lean mass of
      the OM was determined by DXA. TT and serum hormone binding globulin (SHBG) were
      assayed by ELISA and used to calculate FT. AR CAGn was determined using
      polymerase chain reaction and microchip electrophoresis. OM were weaker than YM (
      20 to -29%, all P<0.001), and serum androgens were lower (TT, -13%; FT, -13%;
      both P<0.001). TT was unrelated to any strength measurement in YM or OM. In the
      OM only, FT had a weak positive association with all three strength measures
      (r(2)=4.1-9.3%, P<0.036) and both whole body and thigh lean mass (r(2)=6.1-8.6%;
      P<0.013). Muscle strength was unrelated to AR CAGn for either the YM or OM, or
      when data were collapsed across both age groups (age normalised strength). Lean
      mass in the older cohort was also independent of AR CAGn. In conclusion, FT, but
      not TT or AR CAGn, was positively associated with muscle strength, but only as
      values declined with age.

PMID- 22484018
TI  - The cochlea as an independent neuroendocrine organ: expression and possible roles
      of a local hypothalamic-pituitary-adrenal axis-equivalent signaling system.
AB  - A key property possessed by the mammalian cochlea is its ability to dynamically
      alter its own sensitivity. Because hair cells and ganglion cells are prone to
      damage following exposure to loud sound, extant mechanisms limiting cochlear
      damage include modulation involving both the mechanical (via outer hair cell
      motility) and neural signaling (via inner hair cell-ganglion cell synapses) steps
      of peripheral auditory processing. Feedback systems such as that embodied by the
      olivocochlear system can alter sensitivity, but respond only after stimulus
      encoding, allowing potentially damaging sounds to impact the inner ear before
      sensitivity is adjusted. Less well characterized are potential cellular signaling
      systems involved in protection against metabolic stress and resultant damage.
      Although pharmacological manipulation of the olivocochlear system may hold some
      promise for attenuating cochlear damage, targeting this system may still allow
      damage to occur that does not depend on a fully functional feedback loop for its
      mitigation. Thus, understanding endogenous cell signaling systems involved in
      cochlear protection may lead to new strategies and therapies for prevention of
      cochlear damage and consequent hearing loss. We have recently discovered a novel
      cochlear signaling system that is molecularly equivalent to the classic
      hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system
      functions to balance auditory sensitivity and susceptibility to noise-induced
      hearing loss, and also protects against cellular metabolic insults resulting from
      exposures to ototoxic drugs. This system may represent a local cellular response
      system designed to mitigate damage arising from various types of insult.

PMID- 22484020
TI  - Clinical, surgical, and histopathologic outcomes following failed medical
      abortion.
AB  - OBJECTIVE: To address the consequences of surgical curettage following failed
      medical abortion. METHODS: A retrospective case-control study was performed in a
      tertiary gynecologic department. The case group comprised 104 women who underwent
      surgical curettage following failed medical abortion; the control group included
      104 women who underwent early surgically induced abortion. Clinical
      characteristics and surgical findings were examined. The extent of inflammation
      was quantified following immunohistochemical staining for cell-surface markers
      characteristic of T lymphocytes, B lymphocytes, and macrophages. The extent of
      necrosis was evaluated morphologically. RESULTS: Abnormal findings during
      surgical curettage were significantly more prevalent among women in the case
      group than in the control group (10.6% versus 1.9%; P=0.019). The most frequent
      abnormality in the case group was the presence of intimately adherent products of
      conception, necessitating sharp curettage. The extent of inflammation
      (represented by increased numbers of T and B lymphocytes) was greater in the case
      group than in the control group (P=0.046 and P=0.001, respectively), as was the
      extent of necrosis (P<0.05). CONCLUSION: Curettage following failed medical
      abortion harbors particular difficulties, which may be attributed to an
      inflammatory response. The long-term consequences of curettage following failed
      medical abortion warrant further investigation.

PMID- 22484021
TI  - The functional variant V433M of the CYP4F2 and the metabolic syndrome in Swedes.
AB  - BACKGROUND AND AIM: The genetic basis of Metabolic syndrome (MetS) is largely
      unknown but a link with salt sensitivity is recognized. The cytochrome P450
      isoform 4F2 (CYP4F2) is involved in renal production of 20
      hydroxyeicosatethraenoic acid (20-HETE), a natriuretic substance associated with
      salt sensitivity. The same enzyme is implicated in omega-hydroxylation of very
      long and medium chain fatty acids in the liver suggesting its possible influence
      on gluco-metabolic components of MetS. The aim of the present study was to
      evaluate the effect of CYP4F2 V433M, a functional polymorphism previously
      associated with hypertension via renal salt reabsorption, on the individual
      components of MetS and MetS itself. METHODS: The polymorphism was genotyped in
      the cardiovascular cohort of the Malmo Diet and Cancer (MDC-CVA) study and
      successively in the Malmo Preventive Project (MPP) cohort. Different definitions
      of the MetS were applied. RESULTS: In the MDC-CVA, male, but not female, CYP4F2
      M433 carriers had significantly higher levels of waist, triglycerides, BP and a
      composite sum of MetS phenotypes (MetS score) beside lower HDL-cholesterol
      respect to V-homozygotes. MetS, as defined in the ATPIII and the AHA/NHLBI
      definitions, was more prevalent in M-carriers with respect to V-homozygotes. In
      the MPP cohort, significant association was detectable only for triglycerides at
      baseline and for Diastolic BP at reinvestigation in male M-carriers. CONCLUSION:
      The initial positive association of the CYP4F2 V433M polymorphism with components
      of MetS and MetS itself, found in MDC-CVA, was partially denied in another large
      cohort. The first association either could be due to a false positive result or
      alternatively, different genetic background or population stratification could
      have hidden the effect of the polymorphism in the replication cohort.

PMID- 22484022
TI  - Efficient metal-specific transcription activation by Drosophila MTF-1 requires
      conserved cysteine residues in the carboxy-terminal domain.
AB  - MTF-1 is a sequence-specific DNA binding protein that activates the transcription
      of metal responsive genes. The extent of activation is dependent on the nature of
      the metal challenge. Here we identify separate regions within the Drosophila MTF
      1 (dMTF-1) protein that are required for efficient copper- versus cadmium-induced
      transcription. dMTF-1 contains a number of potential metal binding regions that
      might allow metal discrimination including a DNA binding domain containing six
      zinc fingers and a highly conserved cysteine-rich C-terminus. We find that four
      of the zinc fingers in the DNA binding domain are essential for function but the
      DNA binding domain does not contribute to the metal discrimination by dMTF-1. We
      find that the conserved C-terminus of the cysteine-rich domain provides cadmium
      specificity while copper specificity maps to the previously described copper
      binding region (Chen et al.). In addition, both metal specific domains are
      autorepressive in the absence of metal and contribute to the low level of basal
      transcription from metal inducible promoters.

PMID- 22484023
TI  - The association between social anhedonia, withdrawal and psychotic experiences in
      general and high-risk populations.
AB  - BACKGROUND: Social anhedonia (SA) and withdrawal are clinically relevant
      phenomena in schizophrenia. To examine the nature of the overlap between SA,
      withdrawal and positive symptoms, we investigated whether the co-occurrence of
      these phenotypes is more prominent in siblings of patients with a psychotic
      disorder compared to healthy controls, and if this association is independent of
      the amount of distress caused by psychotic experiences (PEs). METHOD: Data were
      derived from 646 unaffected siblings and 326 healthy controls who were included
      in the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. PEs were
      assessed with the Community Assessment of Psychic Experiences and the Structured
      Interview for Schizotypy-Revised was used to examine social anhedonia and
      withdrawal. RESULTS: Our results show relatively small but significant cross
      sectional associations between SA, withdrawal and PEs in unaffected siblings and
      none in the control group, irrespective of the level of distress caused by PEs.
      CONCLUSIONS: The findings of the present study suggest that the overlap between
      SA, withdrawal and psychotic symptoms often reported in schizophrenia patients,
      may at least partly reflect a shared genetic vulnerability, instead of merely
      being either a state marker of - or reaction to - acute psychotic symptoms.

PMID- 22484024
TI  - Publication bias in meta-analyses of the efficacy of psychotherapeutic
      interventions for schizophrenia.
AB  - OBJECTIVE: Meta-analyses are prone to publication bias, the problem of selective
      publication of studies with positive results. It is unclear whether the efficacy
      of psychotherapeutic interventions for schizophrenia is overestimated due to this
      problem. This study aims at enhancing the validity of the results of meta
      analyses by investigating the degree and impact of publication bias. METHOD: Begg
      and Mazumdar's adjusted rank correlation test, Egger's regression analysis and
      the trim and fill procedure were applied to all systematic reviews up to
      September 2010 that reported the necessary data to assess publication bias.
      RESULTS: We examined 22 data sets, reported in 10 meta-analyses, for indications
      of publication bias. Begg's test indicated significant bias in 2 (9.09%) of these
      data sets, while Egger's test found bias in 3 (13.64%) of the data sets. The
      correction by the trim and fill procedure changed the significance of an effect
      size only once (4.55%), and did so unexpectedly in favor of the treatment
      condition. Psychosocial family interventions, regarding the outcome measure
      "leaving study early" in the time period between 13 and 24 months, were shown to
      be efficacious. DISCUSSION: Overall, we found only moderate evidence for the
      presence of publication bias. With one notable exception, the pattern of efficacy
      of psychotherapy for schizophrenia was not changed in the data sets in which
      publication bias was found. Several efficacious therapies exist, and their
      efficacy does not seem to be the result of publication bias.

PMID- 22484025
TI  - Hemodynamic impact of dexmedetomidine administration in 15,656 noncardiac
      surgical cases.
AB  - STUDY OBJECTIVE: To assess the hemodynamic impact of dexmedetomidine
      administration in a large cohort of patients undergoing routine noncardiac
      surgery. DESIGN: Retrospective database analysis. SETTING: Major academic medical
      center. MEASUREMENTS: A valid electronic preoperative history and physical record
      and electronic perioperative anesthesia record of all adults undergoing
      noncardiothoracic procedures of > 60 minutes duration between January 2007 and
      September 2008 were reviewed. The primary composite endpoint was systolic blood
      pressure < 80 mmHg for > 5 minutes, heart rate < 40 bpm for > 5 minutes, or
      administration of vasoconstrictors (> 500 MUg of phenylephrine by bolus or
      infusion or any epinephrine) or atropine intraoperatively. MAIN RESULTS: A total
      of 15,656 cases, of whom 2,688 (17%) received dexmedetomidine preoperatively or
      intraoperatively and 12,968 (83%) did not receive dexmedetomidine, was
      identified. A significantly higher percentage of patients in the dexmedetomidine
      group met the composite endpoint criteria (27% vs 19%, P < 0.0001). However,
      there was no significant difference in the overall incidence of intraoperative
      hypotension (5.3% dexmedetomidine, 6% no dexmedetomidine) or bradycardia (0.4% in
      both groups). Dexmedetomidine patients received more phenylephrine or atropine
      (23% vs 15%, P < 0.0001). CONCLUSIONS: In a large cohort of routine clinical
      practice cases, dexmedetomidine administration was not associated with more
      hypotension or bradycardia.

PMID- 22484026
TI  - Comparing vertical and coracoid approaches for infraclavicular block in
      orthopedic surgery of the forearm and hand.
AB  - STUDY OBJECTIVE: To determine if there is a difference between the vertical and
      coracoid approaches to the infraclavicular block. DESIGN: Randomized, double
      blinded clinical trial. SETTING: University-affiliated medical center. PATIENTS:
      60 ASA physical status 1 and 2 patients undergoing surgery of the forearm and
      hand. INTERVENTIONS: Patients were randomized to two groups: Group VIP (vertical
      infraclavicular approach; n=30) and Group Coracoid (coracoid infraclavicular
      approach; n=30). In the infraclavicular coracoid approach, the coracoid process
      was used as the landmark. Needle positioning was guided by nerve stimulation.
      MEASUREMENT: For each approach, the quality of sensory and motor block was
      assessed and recorded separately for each of the 4 major nerves of the upper
      limb. MAIN RESULTS: The infraclavicular coracoid approach (11+/-1 min) was faster
      to perform than the vertical infraclavicular block (14+/-1 min; P < 0.05). The
      infraclavicular coracoid approach yielded a shorter sensory block onset time
      (2.3+/-1.3 vs 3+/-1.3 min; P < 0.05). In the coracoid group, a pronounced sensory
      and motor block was noted in the area innervated by the musculocutaneous nerve (P
      < 0.05). CONCLUSION: The coracoid approach is convenient to perform with
      extensive block, and is thus an appropriate alternative to the vertical approach
      in infraclavicular block.

PMID- 22484027
TI  - Clinical disability progression and platelet GP IIb/IIIa values in patients with
      atopic myelitis.
AB  - We aimed to clarify the disability progression and platelet aggregative function
      in atopic myelitis (AM). Seventeen AM patients and 35 healthy controls were
      subjected to clinico-allergological evaluations and glycoprotein IIb/IIIa (GP
      IIb/IIIa) measurements using a VerifyNow assay system. In AM patients, the
      disease duration had significant positive correlations with the Kurtzke Expanded
      Disability Status Scale scores and Sensory Functional Scale scores. The GP
      IIb/IIIa values were significantly higher in AM patients than in controls as well
      as in females compared with males. AM is essentially a progressive disease
      affecting the sensory system, and involves an increased platelet aggregative
      function.

PMID- 22484028
TI  - Regulation and actions of insulin-like growth factors in the ovary of zebrafish
      (Danio rerio).
AB  - Insulin-like growth factors (Igf) are known paracrine/autocrine regulators of
      ovarian development in teleosts. Initial studies investigated the hormonal and
      intracellular signalling cascades involved in regulating the expression of
      ovarian-derived Igfs in zebrafish (Danio rerio). Quantitative real-time PCR was
      used to quantify the expression of igf3, igf2a, and igf2b in full grown immature
      (FG; 0.57-0.65 mm) and mid-vitellogenic (MV; 0.45-0.56 mm) follicles. Addition of
      the gonadotropin analogue human chorionic gonadotropin (hCG) and the adenylate
      cyclase activator forskolin increased igf3 expression in FG and MV follicles, but
      had no effect on igf2a or igf2b expression. The effects of hCG on igf3 expression
      were blocked by the addition of the protein kinase A inhibitor H-89. Pituitary
      adenylate cyclase activating peptide also stimulated a small increase in igf3
      expression in FG follicles, while growth hormone and salmon gonadotropin
      releasing hormone had no effect on igf3, igf2a, or igf2b expression. Secondary
      studies investigated the involvement of ovarian-derived Igfs in mediating the
      ovarian actions of gonadotropins on cell survival and steroidogenesis. Treatment
      of FG follicles with recombinant human IGF1, hCG, or forskolin inhibited the
      induction of caspase-3/7 activity, which was used as a measure of apoptosis. The
      effects of hCG and forskolin on caspase-3/7 were attenuated by co-treatment with
      NVP-AEW54, an IGF1 receptor antagonist. In other studies, hCG was shown to
      increase the production of the maturation-inducing steroid 17,20beta-dihydroxy-4
      pregnen-3-one, but this action was not affected by co-treatment with NVP-AEW54.
      These results suggest there is a high degree of hormonal specificity in
      regulating Igfs in the zebrafish ovary and the ovarian-derived Igfs, presumably
      Igf3, are downstream mediators of gonadotropin-dependent cell survival, but are
      not involved in gonadotropin-induced steroidogenesis.

PMID- 22484029
TI  - Protein palmitoylation inhibition by 2-bromopalmitate alters gliding, host cell
      invasion and parasite morphology in Toxoplasma gondii.
AB  - Protein palmitoylation is the reversible covalent attachment of palmitic acid
      onto proteins. This post-translational modification has been shown to play a part
      in diverse processes such as signal transduction, cellular localization and
      regulation of protein activity. Although many aspects of protein palmitoylation
      have been identified in mammalian and yeast cells, little is known of this
      modification in Toxoplasma gondii. In order to determine the functional role of
      protein palmitoylation in T. gondii, tachyzoites were treated with the
      palmitoylation inhibitor 2-bromopalmitate (2-BP). Parasites treated with 2-BP
      displayed a significant increase in non-circular trails which were longer than
      those trails left by non-treated parasites. Furthermore, 2-BP treatment reduced
      the invasion process to the host cells. Long-term treatment of intracellular
      tachyzoites resulted in major changes in parasite morphology and shape in a dose
      dependent manner. These results suggest that palmitoylation could be modifying
      proteins that are key players in gliding, invasion and cytoskeletal proteins in
      T. gondii.

PMID- 22484030
TI  - A comparison of viral fitness and virulence between emergent adenovirus 14p1 and
      prototype adenovirus 14p strains.
AB  - BACKGROUND: Epidemiological studies from the last decade have suggested that the
      morbidity and mortality associated with a newly emergent strain of human
      adenovirus (HAdV-14p1) is greater than other, more prevalent, adenovirus strains.
      Recent molecular analysis identified very minor genetic differences in HAdV-14p1
      compared to prototype HAdV-14p. No studies have evaluated how these differences
      may affect virulence. OBJECTIVE: To compare HAdV-14p1 and HAdV-14p strains for
      competitive fitness and virulence. STUDY DESIGN: We performed in vitro and
      molecular assays to evaluate growth kinetics, cellular infectivity, cytotoxicity,
      and plaque morphology of the two strains. RESULTS: Growth kinetic data showed no
      viral replication at 30 degrees C and minimal differences at 37 degrees C for
      both strains. Cellular infectivity data showed propagation capabilities for both
      strains in a diverse array of cell lines, with human lung and kidney cells having
      the highest propagation potential. Cytotoxicity data indicated cellular distress
      differences induced by both strains of virus in the first 12h, but similar
      distress levels between 12 and 48 h. Plaque morphology assays showed some
      differences in average plaque diameter. CONCLUSIONS: These data suggest that the
      increase in morbidity and mortality observed in recent HAdV-14p1 infections is
      not due to viral growth or cellular infectivity differences from the prototypic
      HAdV-14 strain. While there were some statistically important differences
      detected between strains in cytotoxicity and plaque morphology assays, it seems
      more likely that other factors, such as environmental stressors, co-infections,
      or individual host response are likely contributing to the increase in morbidity.

PMID- 22484031
TI  - Rosuvastatin improves pulse wave reflection by restoring endothelial function.
AB  - One of the major indicators of intact endothelial function is basal nitric oxide
      (NO) activity. Further, it seems to be likely that statin therapy exerts
      beneficial effects on vascular function, at least in part via an improvement of
      NO bioavailability. In the present double-blind crossover study 29
      hypercholesterolemic patients were randomly assigned to receive rosuvastatin and
      placebo for 42days. Pulse wave analysis was assessed after 30min of rest
      (baseline) and after infusion of N(G)-monomethyl-l-arginine (l-NMMA) at the end
      of 42days treatment period. The magnitude of the increase in central augmentation
      index (cAIx) in response to inhibition of NO synthase (NOS) by l-NMMA is
      indicative of basal NO activity. CAIx was significantly lower (18.3+/-10 versus
      21.9+/-12%, p=0.027) with rosuvastatin compared to placebo. There was no
      increment of cAIx in response to l-NMMA in placebo group. In contrast, cAIx
      increased significantly in response to l-NMMA (20.5+/-11 versus 25.7+/-10mm Hg,
      p=0.001) in rosuvastatin group. The percentage of increase of cAIx tended to be
      more pronounced after treatment with rosuvastatin compared to placebo (53.7+/-92
      versus 14.1+/-36%, p=0.087). Pulse pressure amplification (PPA) improved (1.31+/
      0.2 versus 1.26+/-0.2%, p=0.016) after rosuvastatin compared to placebo.
      Regression analyses revealed that both LDL-cholesterol and CRP-levels are
      independent determinants of basal NO activity improvement, which itself is an
      independent determinant of vascular function, expressed by an improvement of
      pulse wave reflection and PPA. In this placebo controlled study, treatment with
      rosuvastatin improved vascular and endothelial function. Determinants for
      improved NO production in patients with hypercholesterolemia were the achieved
      levels of LDL-cholesterol and CRP. Overall, in patients without CV disease,
      rosuvastatin exerted beneficially effect on vascular dysfunction, one of the
      earliest manifestation of atherosclerosis.

PMID- 22484032
TI  - Muscle endothelial-dependent microvascular dysfunction in adulthood due to early
      postnatal overnutrition.
AB  - The aims of our study were to investigate effects of postnatal overnutrition,
      obtained by restricting the number of pups per litter, on microcirculatory
      reactivity, fat depots, its total percentage and lipid profile. Microvascular
      reactivity was evaluated in the cremaster muscle of 24 hamsters divided into four
      groups, with 6 animals in each one: normal (NL) and restricted (RL) litter
      groups, both at 6th and 21st weeks of age. The NL group had 8-9 pups and the RL 3
      pups per litter and to avoid the litter effect, only one animal was used per
      litter. The results have shown that the RL group had higher velocity of weight,
      body mass and fat gain compared to the NL one at weeks 6 and 21. Significant
      differences were also observed on urogenital fat depot, total cholesterol and low
      density lipoprotein between groups. At the lowest concentration of Ach, the RL
      group showed smaller arteriolar dilatation at the 21st than at the 6th week [5(3
      13) vs 19(8-40)%, p<0.01] while the NL one did not show any difference within the
      group. The highest concentration of Ach at the 21th week pointed to endothelial
      dependent microvascular dysfunction in RL compared to NL [3(8-26) vs. 13(8-26)%,
      p<0.05]. Endothelial-independent microvascular reactivity was similar between
      groups. Our data suggest that postnatal overnutrition is associated to muscle
      endothelial-dependent microvascular dysfunction, greater body mass and total
      percentage of fat and impaired the lipid profile. In conclusion, the imprinting
      promoted by this experimental model of obesity was able to influence
      microvascular reactivity later in life.

PMID- 22484033
TI  - Microtubule assembly-derived by dimerization of TPPP/p25. Evaluation of
      thermodynamic parameters for multiple equilibrium system from ITC data.
AB  - BACKGROUND: The disordered Tubulin Polymerization Promoting Protein/p25
      (TPPP/p25) modulates the dynamics and stability of the microtubule system. In
      this paper the role of dimerization in its microtubule-related functions is
      established, and an approach is proposed to evaluate thermodynamic constants for
      multiple equilibrium systems from ITC measurements. METHODS: For structural
      studies size exclusion chromatography, SDS-PAGE, chemical cross-linking, circular
      dichroism, fluorescence spectroscopy and isothermal titration calorimetry were
      used; the functional effect was analyzed by tubulin polymerization assay.
      Numerical simulation of the multiple equilibrium was performed with Mathematica
      software. RESULTS: The dimerization of TPPP/p25 is promoted by elevation of the
      protein concentration and by GTP addition. The dimeric form displaying enhanced
      tubulin polymerization promoting activity is stabilized by disulfide bond or
      chemical cross-linking. The GTP binding to the dimeric form (Kd-GTP=200 MUM) is
      tighter with one order of magnitude than to the monomeric one leading to the
      enrichment of the dimers. A mathematical model elaborated for the multiple
      equilibrium of the TPPP/p25-GTP system was validated by fitting the GTP-dependent
      changes of ellipticity and fluorescence signal in the course of TPPP/p25
      titrations. The evaluation of the equilibrium constants rendered it possible to
      determine the thermodynamic parameters of the association of different TPPP/p25
      forms with GTP from ITC measurements. CONCLUSIONS/GENERAL SIGNIFICANCE: The
      dimerization of TPPP/p25 with favorable physiological functional potency is
      proposed to play significant role in the fine tuning of TPPP/p25-mediated
      microtubule assembly; the unfolded monomers might be involved in the formation of
      pathological inclusions characteristic for Parkinson's disease and other
      synucleinopathies.

PMID- 22484034
TI  - PFOS-induced hepatic steatosis, the mechanistic actions on beta-oxidation and
      lipid transport.
AB  - BACKGROUND: Perfluorooctane sulfonate (PFOS) was produced by various industries
      and was widely used in diverse consumer products. Human sample analysis indicated
      PFOS contamination in body fluids. Animal studies revealed that PFOS tends to
      accumulate in livers and is able to induce hepatomegaly. However the underlying
      mechanism of PFOS-elicited hepatotoxicity has not yet been fully addressed. The
      objective of this study is to identify the cellular target of PFOS and to reveal
      the mechanisms of PFOS-induced toxicity. METHODS: In this study, mature 8-week
      old male CD-1 mice were administered 0, 1, 5 or 10 mg/kg/day PFOS for 3, 7, 14 or
      21 days. Histological analysis of liver sections, and biochemical/molecular
      analysis of biomarkers for hepatic lipid metabolism were assessed. RESULTS: PFOS
      induced steatosis was observed in a time- and dose-dependent manner. The gene
      expression levels of fatty acid translocase (FAT/CD36) and lipoprotein lipase
      (Lpl) were significantly increased by 10 and/or 5 mg/kg PFOS. Serum levels of
      very-low density lipoprotein were decreased by 14 days of PFOS exposure (p<0.05).
      The rate of mitochondrial beta-oxidation was also found to be significantly
      reduced, leading to the restriction of fatty acid oxidation for energy
      production. CONCLUSION: Taken together, the disturbance of lipid metabolism leads
      to the accumulation of excessive fatty acids and triglycerides in hepatocytes.
      GENERAL SIGNIFICANCE: Since PFOS-elicited pathological manifestation resembles
      one of the most common human liver diseases-nonalcoholic fatty liver disease,
      environmental exposure to PFOS may attribute to the disease progression.

PMID- 22484035
TI  - Isolation of antibodies against different protein conformations using
      immunoaffinity chromatography.
AB  - A polyclonal antiserum obtained after the immunization of a rabbit with
      recombinant human sperm-specific glyceraldehyde-3-phosphate dehydrogenase lacking
      in 68 N-terminal amino acid residues (dN-GAPDS) was purified using different
      immunosorbents with immobilized dN-GAPDS in the native or denatured states. The
      procedure resulted in isolation of two types of polyclonal antibodies. The first
      type interacted with native recombinant dN-GAPDS as well as with native human
      sperm-specific glyceraldehyde-3-phosphate dehydrogenase, not cross-reacting with
      muscle glyceraldehyde-3-phosphate dehydrogenase (GAPD). The second type
      interacted with both native and denatured forms of the sperm-specific proteins,
      exhibiting some cross-reaction with GAPD. Thus, the suggested approach allows
      isolation of the antibodies against conformational or linear epitopes from the
      same polyclonal serum.

PMID- 22484036
TI  - Soymilk: an effective and inexpensive blocking agent for immunoblotting.
AB  - Blocking efficacy of whole soymilk, nonfat soymilk, SuperBlock, and nonfat milk
      was evaluated by performing standard protein immunoblotting procedures on both
      purified protein and crude nuclear extracts from HEK 293 cells. Nonfat soymilk
      was found to have superior blocking efficacy compared with other blocking agents
      in terms of high signal-to-noise ratio with the shortest blocking times. In
      addition, the presence of low concentrations of the detergent Tween 20 (0.05
      0.1%, v/v) in the wash buffer as well as antibody incubations significantly
      lessened the background compared with including only the detergent during wash
      steps.

PMID- 22484037
TI  - A urea electrochemical sensor based on molecularly imprinted chitosan film doping
      with CdS quantum dots.
AB  - An improved imprinted film-based electrochemical sensor for urea recognition was
      developed using CdS quantum dots (QDs) doped chitosan as the functional matrix.
      The microstructure and composition of the imprinted films depicted by scanning
      electron microscopy (SEM), attenuated total reflection infrared (ATR-IR), X-ray
      diffraction (XRD), and electrochemical impedance spectroscopy (EIS) indicated the
      fabricated feasibility of the nanoparticle doped films via in situ
      electrodeposition. Differential pulse voltammetric responses under the optimal
      fabrication conditions showed that the sensitivity of CdS QDs-MIP (molecularly
      imprinted polymer) electrochemical sensor was enhanced from the favorable
      electron transfer and magnified surface area of CdS QDs with a short adsorption
      equilibrium time (7 min), wide linear range (5.0 * 10(-12) to 4.0 * 10(-10) M and
      5.0 * 10(-10) to 7.0 * 10(-8) M), and low detection limit (1.0 * 10(-12) M).
      Meanwhile, the fabricated sensor showed excellent specific recognition to
      template molecule among the structural similarities and coexistence substances.
      Furthermore, the proposed sensor was applied to determine the urea in human blood
      serum samples based on its good reproducibility and stability, and the acceptable
      recovery implied its feasibility for practical application.

PMID- 22484038
TI  - Vibrational circular dichroism study of polypeptide model-membrane systems.
AB  - In this article, we describe the mutual structural effect of the interaction
      between the model membranes and polylysine and poly-l-arginine. Vibrational
      circular dichroism (VCD), a method exceptionally sensitive to the polypeptide
      structure that has not been established in such studies before, was the primary
      method of this study. A complementary technique, electronic circular dichroism,
      was applied to verify the newly obtained results and as a bridge to the previous
      studies. We used micelles composed of sodium dodecyl sulfate (SDS) as a monolayer
      membrane model and large unilamellar vesicles composed of phospholipids as a
      bilayer membrane model. We describe the conformational changes of the
      polypeptides caused by the interaction with the model membranes. Among others,
      the presence of the liposomes in the solution generated special conditions for
      the formation of the alpha-helical structure of poly-l-arginine; the presence of
      SDS induced the formation of the beta-structure of polylysine. From a
      methodological point of view, we emphasize the advantages of infrared
      spectroscopic techniques for the liposomic membrane studies as well as the
      preference of ultraviolet techniques for smaller micellar systems.

PMID- 22484039
TI  - Negative staining of lipopolysaccharides on polyacrylamide gels by using eosin B.
AB  - A sensitive and simple technique for the negative detection of
      lipopolysaccharides (LPSs) following polyacrylamide gel electrophoresis (PAGE)
      using eosin B (EB) was developed. After electrophoresis, gels were fixed,
      stained, and developed within 30 min to achieve transparent and colorless LPS
      bands under opaque gel matrix background. As low as 20 to 40 ng of total LPSs
      could be detected, which is 4-fold more sensitive than those of the widely used
      silver stain developed by Fomsgaard and coworkers and imidazole-zinc (IZ)
      negative stain. For its sensitivity and brevity, this stain may be a practical
      method for LPS determination in the routine laboratory.

PMID- 22484040
TI  - A fluorescence-based analysis of aristolochic acid-derived DNA adducts.
AB  - Aristolochic acids (AAs), major components of plant extracts from Aristolochia
      species, form (after metabolic activation) pro-mutagenic DNA adducts in renal
      tissue. The DNA adducts can be used as biomarkers for studies of AA toxicity.
      Identification of these adducts is a complicated and time-consuming procedure. We
      present here a fast, nonisotopic, fluorescence-based assay for the detection of
      AA-DNA adducts in multiple samples. This approach allows analysis of AA adducts
      in synthetic DNA with known nucleotide composition and analysis of DNA adducts
      formed from chemically diverse AAs in vitro. The method can be applied to compare
      AA-DNA adduct formation in cells and tissues.

PMID- 22484041
TI  - Quantification of dye-mediated photodamage during single-molecule DNA imaging.
AB  - Single-molecule fluorescence imaging of DNA-binding proteins has enabled detailed
      investigations of their interactions. However, the intercalating dyes used to
      visually locate DNA molecules have the undesirable effect of photochemically
      damaging the DNA through radical intermediaries. Unfortunately, this damage
      occurs as single-strand breaks (SSBs), which are visually undetectable but can
      heavily influence protein behavior. We investigated the formation of SSBs on DNA
      molecules by the dye YOYO-1 using complementary single-molecule imaging and gel
      electrophoresis-based damage assays. The single-molecule assay imaged
      hydrodynamically elongated lambda DNA, enabling the real-time detection of double
      strand breaks (DSBs). The gel assay, which used supercoiled plasmid DNA, was
      sensitive to both SSBs and DSBs. This enabled the quantification of SSBs that
      precede DSB formation. Using the parameters determined from the gel damage assay,
      we applied a model of stochastic DNA damage to the time-resolved DNA breakage
      data, extracting the rates of single-strand breakage at two dye staining ratios
      and measuring the damage reduction from the radical scavengers ascorbic acid and
      beta-mercaptoethanol. These results enable the estimation of the number of SSBs
      that occur during imaging and are scalable over a wide range of laser intensities
      used in fluorescence microscopy.

PMID- 22484042
TI  - Water-soluble Ag(2)S quantum dots for near-infrared fluorescence imaging in vivo.
AB  - A one-step method for synthesizing water-soluble Ag(2)S quantum dots terminated
      with carboxylic acid group has been reported. The crystal structure and surface
      of the prepared Ag(2)S quantum dots were characterized. The prepared Ag(2)S
      quantum dots exhibited bright photoluminescence and excellent photostabilities.
      The photoluminescence emissions could be tuned from visible region to near
      infrared (NIR) region (from 510 nm to 1221 nm). Ultra-small sized Ag(2)S
      nanoclusters were synthesized with high initial monomer concentration in the
      current system. The in vivo imaging experiments of nude mice showed that the NIR
      photoluminescence of the prepared Ag(2)S quantum dots could penetrate the body of
      mice. Compared to the conventional NIR quantum dots, the Ag(2)S quantum dots
      don't contain toxic elements to body (such as Cd and Pb), thus, the prepared
      Ag(2)S quantum dots could serve as excellent NIR optical imaging probes and would
      open the opportunity to study nanodiagnostics and imaging in vivo.

PMID- 22484043
TI  - Precise glioma targeting of and penetration by aptamer and peptide dual
      functioned nanoparticles.
AB  - The treatment of a brain glioma is still one of the most difficult challenges in
      oncology. To effectively treat brain glioma and reduce the side effects, drugs
      must be transported across the blood brain barrier (BBB) and then targeted to the
      brain cancer cells because most anti-tumor drugs are highly toxic to the normal
      brain tissue. A cascade delivery strategy was developed to perform these two aims
      and to achieve enhanced and precisely targeted delivery. Herein, we utilize a
      phage-displayed TGN peptide and an AS1411 aptamer, which are specific targeting
      ligands of the BBB and cancer cells, respectively and we conjugate them with
      nanoparticles to establish the brain glioma cascade delivery system (AsTNP). In
      vitro cell uptake and three-dimensional tumor spheroid penetration studies
      demonstrated that the system could not only target endothelial and tumor cells
      but also penetrate the endothelial monolayers and tumor cells to reach the core
      of the tumor spheroids, which was extremely important but mostly ignored in
      glioma therapy. In vivo imaging further demonstrated that the AsTNP provided the
      highest tumor distribution and tumor/normal brain ratio. The distribution was
      also reconfirmed by fluorescent images of the brain slides. As a result, the
      docetaxel-loaded AsTNP presents the best anti-glioma effect with improved glioma
      bearing survival. In conclusion, the AsTNP could precisely target to the brain
      glioma, which was a valuable target for glioma imaging and therapy.

PMID- 22484044
TI  - Multidrug release based on microneedle arrays filled with pH-responsive PLGA
      hollow microspheres.
AB  - This work presents an approach to codelivering transdermally two model drugs,
      Alexa 488 and Cy5, in sequence, based on a system of polyvinylpyrrolidone
      microneedles (PVP MNs) that contain pH-responsive poly(d,l-lactic-co-glycolic
      acid) hollow microspheres (PLGA HMs). The MN system provides the green
      fluorescence of Alexa 488 in PVP MNs, the red fluorescence of the DiI-labeled
      PLGA shell of HMs, and the cyan fluorescence of Cy5 in their aqueous core.
      Combined together, the prepared MN arrays support the localization of the HMs and
      the monitoring of the release profiles of model drugs within the skin tissues.
      The key component of this system is NaHCO(3), which can be easily incorporated
      into HMs. After HMs are treated with an acidic solution (simulating the skin pH
      environment), protons (H(+)) can rapidly diffuse through the free volume in the
      PLGA shells to react with NaHCO(3) and form a large number of CO(2) bubbles. This
      effect generates pressure inside the HMs and creates pores inside their PLGA
      shells, releasing the encapsulated Cy5. Test MNs were strong enough to be
      inserted into rat skin without breaking. The PVP MNs were significantly dissolved
      within minutes, and the first model drug Alexa 488, together with HMs, were
      successfully deposited into the tissues. Once in the acidic environment of the
      skin, the released HMs started to release Cy5 and continued to spread throughout
      the neighboring tissues, in a second step of the release of the drug. This
      approach can be used clinically to codeliver sequentially and transcutaneously a
      broad range of drugs.

PMID- 22484045
TI  - Photosensitizer encapsulated organically modified silica nanoparticles for direct
      two-photon photodynamic therapy and in vivo functional imaging.
AB  - Nanoparticle-assisted two-photon imaging and near infrared (NIR) imaging are two
      important technologies in biophotonics research. In the present paper,
      organically modified silica (ORMOSIL) nanoparticles encapsulated with either PpIX
      (protoporphyrin IX) photosensitizers or IR-820 NIR fluorophores were synthesized
      and optically characterized. Using the former ORMOSIL nanoparticles, we showed:
      (i) direct excitation of the fluorescence of PpIX through its efficient two
      photon absorption in the intracellular environment of tumor cells, and (ii)
      cytotoxicity towards tumor cells by PpIX under two-photon irradiation. The latter
      ORMOSIL nanoparticles can be used as efficient NIR fluorescent contrast agents
      for various types in vivo animal imaging. We applied IR-820 doped ORMOSIL
      nanoparticles in in vivo brain imaging of mice. We also demonstrated the
      applications of them to sentinel lymph node (SLN) mapping of mice. Finally, we
      showed that the nanoprobes could target the subcutaneously xenografted tumor of a
      mouse for long time observations. ORMOSIL nanoparticles have great potentials for
      disease diagnosis and clinical therapies.

PMID- 22484046
TI  - Spatially controlled carbon sponge for targeting internalized radioactive
      materials in human body.
AB  - Carbon sponge, an adsorbent with spatially controlled structure is demonstrated
      for targeting internalized radiocesium and other radionuclides in human body.
      Three dimensionally ordered macroporous (3DOM) carbons derived from inverse opal
      replicas of colloidal-crystal template exhibit large surface area and high
      porosity, resulting in highly efficient adsorbents for radionuclides. It is also
      possible to enhance binding affinity and selectivity to radionuclide targets by
      decoration of 3DOM carbon surfaces with Prussian blue (PB) nanoparticles, and
      synthesized PB nanoparticles reveal low toxicity toward macrophage cells with
      potential advantages over oral administration. It is noteworthy that the maximum
      (133)Cs adsorption capacity of PB-decorated 3DOM carbons is 40.07 mmol g(-1)
      which is ca. 30 and 200 times higher than that of commercialized medicine
      Radiogardase((r)) and bulk PB, respectively. Further, adsorption kinetics study
      indicates that the PB-decorated 3DOM carbons have the homogenous surface for
      (133)Cs ion adsorption and all sites have equal adsorption energies in terms of
      ion exchange between the cyano groups of the PB-decorated 3DOM carbons and
      radionuclides. As a concept of the oral-administrable "carbon sponge", the PB
      decorated 3DOM carbons offer useful implications in the separation science of
      radioactive materials and important insight for designing novel materials for
      treatment of patients or suspected internal contamination with radioactive
      materials.

PMID- 22484048
TI  - Arginine functionalized peptide dendrimers as potential gene delivery vehicles.
AB  - The quest for highly efficient and safe gene delivery systems has become the key
      factor for successful application of gene therapy. Peptide dendrimers are
      currently investigated as excellent candidates for non-viral gene delivery
      vectors. In this study, we report the synthesis and characterization of arginine
      functionalized peptide dendrimer-based vectors ranging from 5th generation (G5A)
      to 6th generation (G6A) via click chemistry, and their use for gene transfection
      in vitro and in vivo. The dendrimers can condense plasmid DNA (pDNA) and protect
      pDNAs from nuclease digestion. Both atomic force microscopy (AFM) and dynamic
      light scattering (DLS) revealed that the sizes of dendrimer/DNA particles were
      within 180-250 nm range. In vitro studies showed that the functionalized peptide
      dendrimers provided serum independent and high transfection efficiency on all
      studied cells, as over 2 fold higher than that of branched polyetherimide (PEI)
      in the presence of serum. Dendrimer G5A with molecular weight of 17 kDa
      demonstrated 6-fold transfection activity than PEI in breast tumor models, as
      well as good biosafety proved by in vitro and in vivo toxicity evaluation.
      However, G6A with molecular weight of 46 kDa showed much higher cytotoxicity. The
      functionalized dendrimer G5A with optimal generation may be therefore a potential
      candidate for gene delivery vehicle.

PMID- 22484047
TI  - Role of sustained antigen release from nanoparticle vaccines in shaping the T
      cell memory phenotype.
AB  - Particulate vaccines are emerging promising technologies for the creation of
      tunable prophylactics against a wide variety of conditions. Vesicular and solid
      biodegradable polymer platforms, exemplified by liposomes and polyesters,
      respectively, are two of the most ubiquitous platforms in vaccine delivery
      studies. Here we directly compared the efficacy of each in a long-term
      immunization study and in protection against a model bacterial antigen.
      Immunization with poly(lactide-co-glycolide) (PLGA) nanoparticles elicited
      prolonged antibody titers compared to liposomes and alum. The magnitude of the
      cellular immune response was also highest in mice vaccinated with PLGA, which
      also showed a higher frequency of effector-like memory T cell phenotype, leading
      to an effective clearance of intracellular bacteria. The difference in
      performance of these two common particulate platforms is shown not to be due to
      material differences but appears to be connected to the kinetics of antigen
      delivery. Thus, this study highlights the importance of sustained antigen release
      mediated by particulate platforms and its role in the long-term appearance of
      effector memory cellular response.

PMID- 22484049
TI  - Gene and doxorubicin co-delivery system for targeting therapy of glioma.
AB  - The combination of gene therapy and chemotherapy is a promising treatment
      strategy for brain gliomas. In this paper, we designed a co-delivery system
      (DGDPT/pORF-hTRAIL) loading chemotherapeutic drug doxorubicin and gene agent pORF
      hTRAIL, and with functions of pH-trigger and cancer targeting. Peptide HAIYPRH
      (T7), a transferrin receptor-specific peptide, was chosen as the ligand to target
      the co-delivery system to the tumor cells expressing transferrin receptors. T7
      modified co-delivery system showed higher efficiency in cellular uptake and gene
      expression than unmodified co-delivery system in U87 MG cells, and accumulated in
      tumor more efficiently in vivo. DOX was covalently conjugated to carrier though
      pH-trigged hydrazone bond. In vitro incubation of the conjugates in buffers led
      to a fast DOX release at pH 5.0 (intracellular environment) while at pH 7.4
      (blood) the conjugates are relatively stable. The combination treatment resulted
      in a synergistic growth inhibition (combination index, CI < 1) in U87 MG cells.
      The synergism effect of DGDPT/pORF-hTRAIL was verified in vitro and in vivo. In
      vivo anti-glioma efficacy study confirmed that DGDPT/pORF-hTRAIL displayed anti
      glioma activity but was less toxic.

PMID- 22484050
TI  - FTIR spectro-imaging of collagens for characterization and grading of gliomas.
AB  - Collagens are a family of at least 30 protein types organized as networks. They
      constitute the main support material of cells under the form of extracellular
      matrix as well as for membranes in vessels, organs, and tissue compartments.
      Collagen network abnormalities are at the origin of many diseases, including
      myopathies and fibroses. The characterization of collagens remains an analytical
      challenge due to the insolubility of these molecules and the difficulty
      encountered in isolating given types without altering their structure or in
      maintaining network organization, which is critical to diagnosing related
      pathologies. We have proposed using a vibrational spectroscopy based imaging
      technique, namely Fourier-transform infrared (FTIR) imaging, for a spatially
      resolved analysis of secondary structure of different collagen types in complex
      samples, and more specifically for characterizing gliomas. With newly developed
      spectral data treatments and chemometrics using secondary structure parameters of
      collagen proteins, FTIR imaging is now able to distinguish between several types.
      On this basis, gliomas have been investigated as specific collagen-rich tissues
      developing in a non-collagenous environment, providing high specificity to this
      FTIR imaging utilization. Here, we review the recent advances in this imaging
      approach for understanding glioma development, with FTIR imaging now being
      proposed as a molecular histopathology tool for clinicians.

PMID- 22484051
TI  - Microbial transformation of antimalarial terpenoids.
AB  - The fungal and bacterial transformation of terpenoids derived from plant
      essential oils, especially the sesquiterpenoid artemisinin from Artemisia annua,
      has produced several new candidate drugs for the treatment of malaria. Obtaining
      new derivatives of terpenoids, including artemisinin derivatives with increased
      antimalarial activity, is an important goal of research in microbial
      biotechnology and medicinal chemistry.

PMID- 22484052
TI  - In situ TEM nanoindentation of nanoparticles.
AB  - The deformation behavior of nanoparticles continues to be an exciting area for
      materials research. Typically, nanoparticles show a conspicuous lack of
      dislocations, even after significant deformation. Therefore, it has been
      suggested that dislocations cannot exist or/do not play a role on the deformation
      of nanoparticles. In situ TEM nanoindentation is a critical tool for addressing
      this issue because it allows for the deformation to be monitored in real time. In
      this article, we discuss some of the experimental needs and challenges for
      performing in situ nanoindentation TEM experiments on nanoparticles. In addition,
      we show both diffraction contrast and phase contrast in situ TEM nanoindentation
      experiments on silver nanoparticles with diameters below 50nm. Evidence of the
      presence of dislocations was observed during deformation, but upon unloading
      dislocations disappeared.

PMID- 22484053
TI  - Evaluation of Cissus quadrangularis extracts as an inhibitor of COX, 5-LOX, and
      proinflammatory mediators.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cissus quadrangularis is an ancient medicinal
      plant. It is an active ingredient of one Ayurvedic formula called "Laksha
      Gogglu". Its stem is used in food preparation in India. Traditionally it is used
      to treat various diseases like asthma, indigestion, ear diseases, irregular
      menstruation, skin diseases, piles, fractured bones, etc. AIM OF THE STUDY: This
      study aimed to evaluate the ability of the plant extracts to inhibit
      cycloxygenase (COX-1), cycloxygenase (COX-2), and 5-lipoxygenase (5-LOX) enzyme
      activity. Western blot analysis was also carried out in the quest to determine
      the effect of active acetone fraction of Cissus quadrangularis (AFCQ) on
      proinflammatory mediators as acetone extract is found to be the most effective in
      this study. MATERIALS AND METHODS: The differential extract of the stem were
      tested for enzyme inhibition of COX and 5-LOX using spectroscopic and
      polarigraphic method. Effective acetone extract was partially purified by silica
      column, one of the active fraction showed dual inhibition against COX and 5-LOX.
      Western blotting shows downregulation of proinflammatory mediators as well as
      upregulation of phase-II enzymes. RESULTS: AFCQ extract showed COX and 5-LOX
      inhibition with IC(50) values of 7 MUg/ml, 0.4 MUg/ml, and 20 MUg/ml for COX-1,
      COX-2 and 5-LOX respectively. It also showed anti-inflammatory activity on RAW
      264.7 cell line with IC(50) value 65 MUg/ml. In addition to this it is showing
      inhibition of proinflammatory mediators like iNOS and TNFalpha, along with
      translocation of Nrf-2 and upregulation of HO-1. CONCLUSION: AFCQ is a COX and 5
      LOX inhibitor isolated from the stems of Cissus quadrangularis. It is also
      effectively downregulate the iNOS, TNFalpha, and upregulation of HO-1.

PMID- 22484054
TI  - Distinct role of matrix metalloproteinase-3 in kidney injury molecule-1 shedding
      by kidney proximal tubular epithelial cells.
AB  - Tubulointerstitial injury is a common pathway in progressive renal impairment and
      human proximal tubular epithelial cells (PTEC) play a crucial role in this
      process. Kidney injury molecule-1 (KIM-1) has received increasing attention due
      to its potential utility as the therapeutic target and biomarker for kidney
      injury. This study aims to explore the underlying mechanism regulating the
      release of KIM-1. Cultured primary human PTEC expressed and released KIM-1 from
      the apical surface through an ectodomain shedding process mediated by matrix
      metalloproteinase (MMP), independent of gene expression and protein synthesis.
      The constitutive KIM-1 shedding by PTEC was enhanced in a dose- and time
      dependent manner by human serum albumin (HSA) or tumor necrosis factor-alpha (TNF
      alpha), two important physiological stimuli found during kidney injury. Data from
      PCR array screening of MMPs gene expression in PTEC following activation by HSA
      or TNF-alpha, and from blocking experiments using either synthetic MMP inhibitors
      or MMP gene knockdown by siRNA, revealed that the constitutive and accelerated
      shedding of KIM-1 in cultured PTEC was mediated by MMP-3. Furthermore, the up
      regulation of MMP-3 and KIM-1 release by PTEC was associated with generation of
      reactive oxygen species. In a mouse model of acute kidney injury induced by
      ischemia and reperfusion, increased expression of MMP-3 and KIM-1 as well as
      their co-localization were observed in kidney from ischemic but not in sham
      operated mice. Taken together, these in vitro and in vivo evidences suggest that
      MMP-3 plays an inductive role in KIM-1 shedding by PTEC.

PMID- 22484055
TI  - Detection of early pregnancy-specific proteins in Holstein milk.
AB  - Bovine pregnancy is commonly diagnosed by rectal palpation or ultrasonography and
      changes in progesterone concentration. To determine a simpler and less expensive
      diagnostic method, we sought to identify early pregnancy-specific proteins in
      bovine milk by comparing samples collected from pregnant and non-pregnant
      Holstein cattle. Of the 600-700 protein spots visible on 2-DE gel images, 39 were
      differentially expressed in milk from pregnant and non-pregnant cattle.
      Antibodies generated against synthetic peptides of milk whey proteins expressed
      specifically during pregnancy were used to confirm protein expression patterns.
      Western blot analysis showed that the levels of expression of lactoferrin
      (lactotransferrin) and alpha1G T-type calcium channel subunit (alpha-1G) were
      higher in samples from pregnant than non-pregnant cattle. These findings suggest
      that assays for pregnancy-specific milk proteins may be used to diagnose
      pregnancy in cattle.

PMID- 22484057
TI  - A proteomics strategy for determining the synthesis and degradation rates of
      individual proteins in fish.
AB  - In order to study the protein dynamics in the tissues of fish we have developed a
      proteomics-based strategy to determine the rates of synthesis and degradation of
      individual proteins. We have demonstrated the feasibility of this approach by
      measuring the turnover of multiple isoforms of parvalbumin (beta1-7) in the
      skeletal muscle of common carp (Cyprinus carpio). A stable isotope-labelled amino
      acid ([(2)H(7)] l-leucine) was administered to the carp via the diet and its
      incorporation into the isoforms of parvalbumin in muscle over time was monitored
      by LC-MS analysis of signature peptides. The relative isotope abundance was
      calculated and used to deconvolute the data. The beta7 parvalbumin isoform had a
      rate of synthesis that was greater than the rate of degradation. In contrast the
      rate of degradation of the beta5 isoform exceeded its rate of synthesis, whilst
      the analysis revealed that the other parvalbumin beta-isoforms (beta1, beta2,
      beta3, beta4 and beta6) had a rate of synthesis that was equal to the rate of
      degradation. This work has addressed a number of technical challenges and
      represents the first study to use proteomic approaches to measure the turnover of
      individual proteins in fish.

PMID- 22484056
TI  - The transcriptome and proteome are altered in marine polychaetes (Annelida)
      exposed to elevated metal levels.
AB  - Polychaetes are often used in toxicological studies to understand mechanisms of
      resistance and for biomarker detection, however, we know of only a few genetic
      pathways involved in resistance. We found the marine polychaete Ophelina sp.1
      (Opheliidae) in sediment containing high copper levels and investigated this
      phenomenon by measuring metal accumulation in the worms and changes in gene and
      protein expression. We sequenced the transcriptome of Ophelina sp.1 from both the
      impacted and reference sediments using 454-sequencing and analysed their
      proteomes using differential in gel electrophoresis (DIGE). We used the sequenced
      transcriptome to guide protein identification. Transcripts coding for the copper
      chaperone, Atox1, were up-regulated in the worms inhabiting the high copper
      sediment. In addition, genes coding for respiratory proteins, detoxification
      proteins and cytoskeletal proteins were significantly altered in metal-exposed
      worms; many of these changes were also detected in the proteome. This dual
      approach has provided a better understanding of heavy metal resistance in
      polychaetes and we now have a wider range of suitable indicator genes and
      proteins for future biomarker development.

PMID- 22484058
TI  - Quantitative analysis of caveolin-rich lipid raft proteins from primary and
      metastatic colorectal cancer clones.
AB  - Caveolin-rich lipid rafts (CLRs) are thickened sections of the cell membrane that
      are composed of the integral membrane proteins caveolins together with saturated
      long chain fatty acids, cholesterol and lipids. Membrane proteins - lipid raft
      proteins in particular - may play important roles in cell signaling and cell-cell
      interaction. Due to their unique structure, CLRs seem to be the preferred docking
      site for specific proteins involved in focal adhesion and cancer metastasis. Our
      objective was thus to identify and quantify CLR proteins from primary and
      metastatic colorectal cancer (CRC) clones. We found differential expression of
      nine CLR proteins from primary and metastatic CRC clones. Among the identified
      proteins, an immune system inhibiting protein was significantly overexpressed in
      the metastatic clone, while cell adhesion and transport molecules were among the
      overexpressed proteins in the primary clone. All the identified CRL proteins are
      involved in tumorigenesis, specifically metastasis, and may thus serve as
      therapeutic targets. A novel concept for identification and quantification of CLR
      proteins with label-free mass spectrometry method was specifically examined in
      this study. Validation of the method against immunoblotting and FACS analysis
      indicates that it can be applied for the identification of novel biomarkers for
      cancer and metastasis.

PMID- 22484059
TI  - Virtual Labs in proteomics: new E-learning tools.
AB  - Web-based educational resources have gained enormous popularity recently and are
      increasingly becoming a part of modern educational systems. Virtual Labs are E
      learning platforms where learners can gain the experience of practical
      experimentation without any direct physical involvement on real bench work. They
      use computerized simulations, models, videos, animations and other instructional
      technologies to create interactive content. Proteomics being one of the most
      rapidly growing fields of the biological sciences is now an important part of
      college and university curriculums. Consequently, many E-learning programs have
      started incorporating the theoretical and practical aspects of different
      proteomic techniques as an element of their course work in the form of Video
      Lectures and Virtual Labs. To this end, recently we have developed a Virtual
      Proteomics Lab at the Indian Institute of Technology Bombay, which demonstrates
      different proteomics techniques, including basic and advanced gel and MS-based
      protein separation and identification techniques, bioinformatics tools and
      molecular docking methods, and their applications in different biological
      samples. This Tutorial will discuss the prominent Virtual Labs featuring
      proteomics content, including the Virtual Proteomics Lab of IIT-Bombay, and E
      resources available for proteomics study that are striving to make proteomic
      techniques and concepts available and accessible to the student and research
      community. This Tutorial is part of the International Proteomics Tutorial
      Programme (IPTP 14). Details can be found at:
      http://www.proteomicstutorials.org/.

PMID- 22484060
TI  - A mechanism for gene-environment interaction in the etiology of congenital
      scoliosis.
AB  - Congenital scoliosis, a lateral curvature of the spine caused by vertebral
      defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that
      haploinsufficiency of Notch signaling pathway genes in humans can cause this
      congenital abnormality. We also show that in a mouse model, the combination of
      this genetic risk factor with an environmental condition (short-term gestational
      hypoxia) significantly increases the penetrance and severity of vertebral
      defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a
      temporary failure of embryonic somitogenesis. Our results potentially provide a
      mechanism for the genesis of a host of common sporadic congenital abnormalities
      through gene-environment interaction.

PMID- 22484061
TI  - A PCR-free cloning method for the targeted phi80 Int-mediated integration of any
      long DNA fragment, bracketed with meganuclease recognition sites, into the
      Escherichia coli chromosome.
AB  - The genetic manipulation of cells is the most promising strategy for designing
      microorganisms with desired traits. The most widely used approaches for
      integrating specific DNA-fragments into the Escherichia coli genome are based on
      bacteriophage site-specific and Red/ET-mediated homologous recombination systems.
      Specifically, the recently developed Dual In/Out integration strategy enables the
      integration of DNA fragments directly into specific chromosomal loci (Minaeva et
      al., 2008). To develop this strategy further, we designed a method for the
      precise cloning of any long DNA fragments from the E. coli chromosome and their
      targeted insertion into the genome that does not require PCR. In this method, the
      region of interest is flanked by I-SceI rare-cutting restriction sites, and the I
      SceI-bracketed region is cloned into the unique I-SceI site of an integrative
      plasmid vector that then enables its targeted insertion into the E. coli
      chromosome via bacteriophage phi80 Int-mediated specialized recombination. This
      approach allows any long specific DNA fragment from the E. coli genome to be
      cloned without a PCR amplification step and reproducibly inserted into any chosen
      chromosomal locus. The developed method could be particularly useful for the
      construction of marker-less and plasmid-less recombinant strains in the
      biotechnology industry.

PMID- 22484062
TI  - Acromegaly.

PMID- 22484063
TI  - Evidence based curriculum design--use of a surgical database to identify non
      perceived needs in educating otolaryngologists on pediatric conditions.
AB  - OBJECTIVE: To identify the common non-otolaryngological diagnoses (N-OD)
      encountered by a pediatric otolaryngologist in surgical patients. This
      information may help in educating otolaryngologists on relevant pediatric
      conditions among their patients. DESIGN/SETTING: Cross-sectional, retrospective
      database review of entries from 2006 to 2008 at a tertiary pediatric centre
      involving the patient case load of a busy pediatric otolaryngologist. MAIN
      OUTCOME MEASURES: The main outcome of this study was to identify the common (N
      OD) encountered by a pediatric otolaryngologist. Conditions excluded from the
      analysis were surgical complications and diagnoses managed primarily by
      otolaryngologists (sleep disordered breathing and allergic rhinitis). RESULTS:
      1357 pediatric surgical entries were identified. Of these, 524 (38.6%) entries
      contained N-OD and underwent surgery. A total of 580 N-OD were identified for
      these 524 patients. The N-OD were identified and categorized into the following
      subheadings: syndromes/associations, respiratory and cardiac, gastrointestinal,
      developmental, metabolic, and miscellaneous conditions. The most common N-OD are
      gastro-esophageal reflux disease, obesity, history of prematurity, congenital
      heart disease, asthma developmental delay and Down syndrome. The commonest
      categories encountered were developmental (138), cardio-respiratory (114) and
      gastro-intestinal (114). CONCLUSIONS: This paper identifies the common N-OD
      encountered by a pediatric otolaryngologist in children managed at a tertiary
      level. The highlighted N-OD may help as a guide on curriculum content for
      training residents and fellows and continued medical education.

PMID- 22484064
TI  - The novel c.247_249delTTC (p.F83del) GJB2 mutation in a family with prelingual
      sensorineural deafness.
AB  - Non-syndromic hearing loss is one of the most common hereditary determined
      diseases in human, and the disease is a genetically heterogeneous disorder.
      Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of non
      syndromic recessive hearing impairment in many countries and are largely
      dependent on ethnic groups. Due to the high frequency of the c.35delG GJB2
      mutation in the Greek population, we have previously suggested that Greek
      patients with sensorineural, non-syndromic deafness should be tested for the
      c.35delG mutation and the coding region of the GJB2 gene should be sequenced in
      c.35delG heterozygotes. Here we present on the clinical and molecular genetic
      evaluation of a family suffering from prelingual, sensorineural, non-syndromic
      deafness. A novel c.247_249delTTC (p.F83del) GJB2 mutation was detected in
      compound heterozygosity with the c.35delG GJB2 mutation in the proband and was
      later confirmed in the father, while the mother was homozygous for the c.35delG
      GJB2 mutation. We conclude that compound heterozygosity of the novel
      c.247_249delTTC (p.F83del) and the c.35delG mutations in the GJB2 gene was the
      cause of deafness in the proband and his father.

PMID- 22484065
TI  - Elaboration and characterization of nanoliposome made of soya; rapeseed and
      salmon lecithins: application to cell culture.
AB  - Health benefits of unsaturated fatty acids have been demonstrated over the last
      decades. Nanotechnology provided new process to produce particles such as
      liposomes and nanoliposomes made of pure phospholipids. These techniques are
      already used in pharmaceutics to augment the bioavailability and the
      bioefficiency of drugs. The aim of this paper is to characterize and evaluate the
      potential of nanoliposomes made of three lecithins (soya, rapeseed and salmon) on
      cell culture in order to use them in the future as drug delivery systems for
      tissue engineering. We began to measure, with zetasizer, the radius size of
      liposomes particles which are 125.5, 136.7 and 130.3 nm respectively for
      rapeseed, soya and salmon lecithin. Simultaneously, solutions observed by TEM
      demonstrated the particles were made much of liposomes than droplet (emulsion).
      Finally, we found that the solutions of lecithins were enough stable over 5 days
      at 37  degrees C to be used in culture medium. We investigated the effect of
      soya, rapeseed and salmon lecithin liposome from 2mg/mL to 5.2 MUg/mL on
      metabolic activity and cell proliferation on rat bone marrow stem cells (rBMSC)
      during 14 days. The results showed that the three lecithins (soya, rapeseed and
      salmon) improve cell proliferation at different concentration.

PMID- 22484066
TI  - Is external cervical orthotic bracing necessary after posterior atlantoaxial
      fusion with modern instrumentation: meta-analysis and review of literature.
AB  - BACKGROUND: No guidelines exist regarding external cervical orthoses (ECO) after
      atlantoaxial fusion. We reviewed published series describing C1-2 posterior
      instrumented fusions with screw-rod constructs (SRC) or transarticular screws
      (TAS) and compared rates of fusion with and without postoperative ECO. METHODS:
      Online databases were searched for English-language articles between 1986 and
      April 2011 describing ECO use after posterior atlantoaxial instrumentation with
      SRC or TAS. Eighteen studies describing 947 patients who had SRC (+/- ECO: 254 of
      693 patients), and 33 studies describing 1424 patients with TAS (+/- ECO: 525 of
      899 patients) met inclusion criteria. Meta-analysis techniques were applied to
      estimate rates of fusion with and without ECO use. RESULTS: All studies provided
      class III evidence, and no studies directly compared outcomes with or without ECO
      use. There was no significant difference in the proportion of patients who
      achieved successful fusion between patients treated with ECO and without ECO for
      SRC or TAS patients. Point estimates and 95% confidence intervals (CI) for rates
      of fusion +/- ECO were 97.4% (CI: 95.2% to 98.6%) versus 97.9% (CI: 93.6% to
      99.3%) for SRC and 93.6% (CI: 90.7% to 95.6%) versus 95.3% (CI: 90.8% to 97.7%)
      for TAS. There was no correlation between duration of ECO treatment and fusion
      (dose effect). CONCLUSIONS: After C1-2 fusion with modern instrumentation, ECO
      may be unnecessary (class III). Some centers recommend ECO use with patients with
      softer bone quality (class IV). Prospective, randomized studies with validated
      radiographic and clinical outcome metrics are necessary to determine the utility
      of ECO after C1-2 fusion and its impact on patient comfort and cost.

PMID- 22484067
TI  - Microsurgical findings of Tolosa-Hunt syndrome.
AB  - BACKGROUND: Tolosa-Hunt syndrome (THS), a nonspecific chronic inflammation of the
      cavernous sinus, is a rarely needed surgical manipulation, even for diagnosis,
      because corticosteroid therapy is markedly effective against this condition.
      METHODS: A 59-year-old man presented with left trigeminal neuralgia and right
      abducens nerve palsy 2 months after the improvement of right oculomotor nerve
      palsy by corticosteroid therapy. Radiological examinations showed a mass lesion
      in the left cavernous sinus. The clinical course indicated THS; however,
      hematological examination showed a positive tuberculous test. We performed a
      biopsy to rule out tuberculoma in the cavernous sinus. RESULTS: The biopsy was
      via a left frontotemporal interdural approach. The dura propria over the
      cavernous sinus was thickened and tightly adhered to the inner layer. The
      cavernous sinus was occupied by whitish elastic-hard tissue, and it was partially
      resected through the anterolateral triangle. Histopathological examination showed
      thick fibrous tissue with numerous degenerated cells and partial inflammatory
      cell infiltrations without any findings of tuberculoma. The final diagnosis was
      THS, and corticosteroid therapy was effective despite the chronic fibrous change
      of the cavernous sinus lesion. CONCLUSIONS: This article presents details of
      surgical findings of THS that have not been demonstrated in any previous reports.

PMID- 22484068
TI  - Comparisons of 30-day mortalities and 90-day functional recoveries after first
      and recurrent primary intracerebral hemorrhage attacks: a multiple-institute
      retrospective study.
AB  - BACKGROUND: The aim of this study was to determine and compare 30-day mortalities
      and 90-day functional recoveries after first and recurrent primary intracerebral
      hemorrhage (PICH) attacks. The investigators sought to identify factors
      predisposing 30-day mortality and functional recovery and to compare patients
      after first and recurrent PICH attacks. METHODS: The medical records of 1856 PICH
      patients treated in Samsung Changwon Hospital and Dong-A University Medical
      Center from January 2000 to December 2010 were retrospectively evaluated.
      RESULTS: Of these 1856 patients, 1499 were included. Mean patient age was 66.4 +/
      16.3 years, and there were 742 male patients (49.5%). Recurrent PICH occurred in
      142 (9.5%) patients. Thirty-day mortality was 13.6% for first PICH patients and
      14.1% for recurrent PICH patients (P = 0.824). Good functional recovery at 90
      days after ictus was achieved by 52.2% of first PICH patients and by 31.0% of
      recurrent patients (P = 0.003). In both groups, multivariate analysis showed that
      unconsciousness, pupillary abnormality, surgery, and underlying disease were
      associated with high mortality, and that consciousness, a lobal location, a small
      hemorrhagic volume, and conservative treatment were associated with good
      functional recovery. After excluding recurrent patients with a previous moderate
      to severe disability due to the sequelae of PICH, no difference was found between
      the first (25.1%) and recurrent groups (19.0%) in terms of functional recovery (P
      = 0.083). CONCLUSIONS: The factors found to predispose clinical outcome were
      similar in the two groups. This study shows that given optimal treatment,
      recurrent PICH patients can achieve the same clinical outcomes as first PICH
      patients.

PMID- 22484069
TI  - Posttraumatic Benedikt's syndrome: a rare entity with unclear anatomopathological
      correlations.
AB  - BACKGROUND: This study sought to present a very rare case of a posttraumatic
      midbrain lesion producing a debilitating constellation of symptoms identified as
      Benedikt's syndrome. METHODS: A 20-year-old woman with traumatic brain injury
      presented with ipsilateral internal and external ophthalmoplegia, and
      contralateral hemiataxia, proprioception disturbances, hypertonicity, slight
      hemiparesis, and hyperactive tendon reflexes. A bibliographic search was
      performed in PubMed. RESULTS: Neuroimaging revealed a left midbrain lesion at the
      level of the superior colliculi. In the literature, virtually all Benedikt's
      syndrome cases, which are rare anyway, are due to midbrain infarcts (basilar or
      posterior cerebral artery branches). There is only one case from 1963, reported
      as a posttraumatic Benedikt-type dyskinesia (French language). The historical
      evolution of the anatomopathologic correlations of the syndrome is also
      discussed. CONCLUSIONS: Benedikt's syndrome is a very rare condition, usually of
      vascular etiology. Our case is just the second one of traumatic pathogenesis ever
      reported, the first in the English language literature.

PMID- 22484070
TI  - Cognitive, physical, and psychological status after intracranial aneurysm
      rupture: a cross-sectional study of a Stockholm case series 1996 to 1999.
AB  - OBJECTIVE: We sought to (1) describe psychological, physical, and cognitive
      functions in patients 10 years after intracranial aneurysm rupture and (2)
      identify any differences in outcome variables between age groups, gender or
      aneurysm locations. METHODS: A consecutive sample of patients (n=217) treated for
      intracranial aneurysm rupture at a neurosurgical clinic in Stockholm, Sweden,
      were followed-up in a cross-sectional design 10.1 years after the onset with
      questionnaires and telephone interviews. The outcome measures were psychological
      functions in terms of symptoms of anxiety or depression and physical and
      cognitive functions. RESULTS: Compared with the reference groups, the aneurysm
      patients scored greater levels of anxiety and depression than normal values.
      Patients with aneurysm rupture in the posterior circulation scored significantly
      more problems with anxiety and depression. Only 2.8% of the patients scored for
      severe physical disability. On a group level, cognition was lower than normal
      population levels; 21.7% of respondents scored below the cut-off value,
      indicating cognitive impairments. CONCLUSIONS: Ten years after aneurysm rupture
      the majority of patients seem to be well-functioning physically, whereas the
      psychological and cognitive functions are affected. A screening of the mental
      health of these patients in connection to radiological follow-up might be helpful
      to identify which patients need further referral to psychiatric treatment for
      anxiety and depression disorders.

PMID- 22484071
TI  - Hangman's fracture in an osteogenesis imperfecta patient.
AB  - BACKGROUND: Traumatic spondylolisthesis of the axis, also known as a hangman's
      fracture, is a well-described entity but is relatively uncommon. There are only
      two published reports of these fractures occurring in pediatric patients with
      osteogenesis imperfecta, a disorder that predisposes patients to long bone
      fractures. CASE DESCRIPTION: We present a unique case of an adult woman with
      osteogenesis imperfecta who sustained an Effendi type II hangman's fracture.
      CONCLUSION: Effendi type II fractures can be conservatively managed via rigid or
      nonrigid cervical orthosis.

PMID- 22484072
TI  - Gamma knife radiosurgery for resectable brain metastasis.
AB  - BACKGROUND: Surgical resection is most often performed for superficially located
      brain metastasis. We evaluate the use of gamma knife radiosurgery (GKS) for
      resectable non-small cell lung cancer (NSCLC) brain metastases located <3 cm away
      from the outer cortical surface. METHODS: Between 1999 and 2009, 306 patients
      were treated for brain metastasis from NSCLC at the University of Virginia. The
      current study included patients with 3 or fewer resectable brain metastases, with
      resectable being defined as <3 cm from the nearest outer cortical surface of the
      brain. Sixty-four patients with 111 metastatic brain lesions were eligible for
      the study. Survival, tumor control, and need for a craniotomy and tumor resection
      after GKS were evaluated. RESULTS: The mean overall survival rate in this cohort
      is 13.5 months (median, 8 months) after GKS, and the mean overall survival after
      diagnosis of the primary lesion was 31.5 months (median, 19 months). Factors
      related to prolonged survival after GKS were gender, Karnofsky performance score
      (KPS), recursive partitioning analysis (RPA) class, age at GKS, number of
      metastatic lesions, development of new intracranial lesions, and number of lobes
      involved with metastatic disease. The actuarial local tumor control rate was 84%
      at 6 months. Two patients (3%) underwent a craniotomy and tumor resection for
      their progressive superficial metastasis after GKS. CONCLUSIONS: GKS for NSCLC
      brain metastases is effective in patients with 3 or fewer resectable tumors. The
      need for a craniotomy in this subgroup of patients after GKS is very low.

PMID- 22484073
TI  - The nervus intermedius: a review of its anatomy, function, pathology, and role in
      neurosurgery.
AB  - BACKGROUND: Geniculate neuralgia, although uncommon, can be a debilitating
      pathology. Unfortunately, a thorough review of this pain syndrome and the
      clinical anatomy, function, and pathology of its most commonly associated nerve,
      the nervus intermedius, is lacking in the literature. Therefore, the present
      study aimed to further elucidate the diagnosis of this pain syndrome and its
      surgical treatment based on a review of the literature. METHODS: Using standard
      search engines, the literature was evaluated for germane reports regarding the
      nervus intermedius and associated pathology. A summary of this body of literature
      is presented. RESULTS: Since 1968, only approximately 50 peer-reviewed reports
      have been published regarding the nervus intermedius. Most of these are single
      case reports and in reference to geniculate neuralgia. No report was a review of
      the literature. CONCLUSIONS: Neuralgia involving the nervus intermedius is
      uncommon, but when present, can be life altering. Microvascular decompression may
      be effective as a treatment. Along its cisternal course, the nerve may be
      difficult to distinguish from the facial nerve. Based on case reports and small
      series, long-term pain control can be seen after nerve sectioning or
      microvascular decompression, but no prospective studies exist. Such studies are
      now necessary to shed light on the efficacy of surgical treatment of nervus
      intermedius neuralgia.

PMID- 22484074
TI  - Onyx embolization of a ruptured lenticulostriate artery aneurysm in a patient
      with moyamoya disease.
AB  - BACKGROUND: Lenticulostriate artery (LSA) aneurysms are uncommon. Most reported
      cases have been surgically treated. There are only three reports of LSA aneurysms
      treated with endovascular techniques. CASE DESCRIPTION: We report the case of a
      49-year-old man who presented with a hemorrhage in the basal ganglia. An
      angiogram revealed a distal LSA aneurysm in the setting of moyamoya disease. The
      patient's aneurysm was successfully embolized by the use of Onyx 18. In this
      report, we present the first case of onyx embolization of a LSA aneurysm and
      review all the previous cases that were managed with endovascular techniques.
      CONCLUSION: Treatment of these lesions with either surgery or endovascular
      therapy is challenging and requires specialized expertise. Given the risks of
      surgery, we believe that LSA aneurysms are best treated by endovascular means,
      especially in the setting of moyamoya disease.

PMID- 22484075
TI  - The "triple-overlay" technique for percutaneous diagnosis and treatment of
      lesions of the head and neck: combined three-dimensional guidance with magnetic
      resonance imaging, cone-beam computed tomography, and fluoroscopy.
AB  - OBJECTIVE: Accurate image guidance is an essential component of percutaneous
      procedures in the head and neck. The combination of preprocedural magnetic
      resonance imaging (MRI) with cone-beam computed tomography (CBCT) and real-time
      fluoroscopy (the "triple-overlay" technique) could be useful in image-guided
      targeting of lesions in the head and neck. METHODS: Three patients underwent
      percutaneous diagnostic or therapeutic procedures of head and neck lesions (mean,
      2.3 +/- 2.4 cm). One patient presented for biopsy of a small lesion in the
      infratemporal fossa only visible on MRI, one presented for preoperative
      embolization of a nasal tumor, and one presented for sclerotherapy of a parotid
      hemangioma. Preprocedural MRI for each case was merged with CBCT to create a
      three-dimensional volume for procedural planning. This was then combined with
      real-time fluoroscopy to create a triple-overlay for needle trajectory and real
      time guidance. RESULTS: The registration of MRI, CBCT, and fluoroscopy was
      successful for all three procedures, allowing 3D manipulation of the combined
      images. Percutaneous procedures were successful in all patients without
      complications. CONCLUSIONS: The combination of MRI, CBCT, and real-time
      fluoroscopy provides detailed anatomical information for 3D image-guided
      percutaneous procedures of the head and neck, especially for small lesions or
      lesions with features visible only by MRI.

PMID- 22484076
TI  - Anterior thigh compartment syndrome and local myonecrosis after posterior spine
      surgery on a Jackson table.
AB  - BACKGROUND: Acute compartment syndrome (ACS) after posterior spinal surgery is
      very uncommon. Most of the reported cases have ACS in the legs related to
      positioning in the knee-chest position; postoperative ACS in the thighs is
      exceedingly rare, with only one reported case (17). CASE DESCRIPTION: This study
      reports two patients who had local muscle necrosis/ACS after spine surgery in the
      prone position and discusses preventive measures. Both of our complications were
      probably related to reversing the position of the iliac crest and hip pads on a
      Jackson operating table, which was done to achieve better lumbar lordosis.
      CONCLUSIONS: Our cases indicate the need for a high index of suspicion of ACS in
      patients who have persistent unresolved pain and local swelling. Tissue pressure
      monitoring is an option in suspected cases. Iliac crest and thigh pads should not
      be reversed during positioning on a Jackson table.

PMID- 22484077
TI  - Mortality and discharge to home after closed brain biopsy: analysis of 3523 cases
      from the State of California, 2003-2009.
AB  - OBJECTIVE: Closed (percutaneous) brain biopsy is an important diagnostic
      procedure. Information on patient outcomes after biopsy come largely from single
      institution series or population-based samples that include patients treated
      during periods that may not reflect current neurosurgical practice. We sought to
      determine the rates of in-hospital mortality and discharge to home after closed
      brain biopsy, and predictors of these outcomes by using a large population-based
      hospital discharge database with near-complete case ascertainment. METHODS: All
      closed brain biopsies performed in nonfederal hospitals within the State of
      California between 2003 and 2009 were identified from a discharge database. Adult
      patients admitted from home were analyzed; patient-level and hospital-level
      factors were reviewed for predictors of in-hospital mortality and discharge to
      home. Logistic regression was used to determine significant predictors of
      outcome. RESULTS: During the 7-year period, 3523 hospitalizations, including
      closed brain biopsy, met our inclusion criteria. Overall in-hospital mortality
      rate was 3.5%, and 67.2% of hospitalizations were followed by discharge directly
      to home. Scheduled versus unscheduled admission and patient race were predictors
      of mortality in multivariate analysis. Patient age, hospital biopsy volume,
      scheduled versus unscheduled admission, and patient race were predictors of
      discharge to home. CONCLUSIONS: Closed brain biopsy is associated with a greater
      rate of mortality than is generally recognized. Most patients are able to return
      to home directly after biopsy, but the rate of discharge to home is lower at
      hospitals with lower procedure volumes.

PMID- 22484078
TI  - gamma knife surgery versus reoperation for recurrent glioblastoma multiforme.
AB  - BACKGROUND: The optimal management of patients with recurrent glioblastoma
      multiforme (GBM) is a subject of controversy. These patients may be candidates
      for both reoperation and/or gamma knife surgery (GKS). Few studies have addressed
      the role of GKS for relapsing gliomas, and the results have not been compared
      with reoperation. To validate the efficacy and safety of GKS, we compared the
      survival and complication rates of GKS and reoperation for recurrent GBMs.
      METHODS: This study retrospectively reviewed 77 consecutive patients with
      histopathologically confirmed GBMs retreated for recurrent GBM between 1996 and
      2007. Thirty-two patients underwent GKS, 26 reoperation and 19 both procedures.
      RESULTS: The median time from the second intervention to tumor progression was
      longer after GKS than after resection, P = 0.009. Median survival after
      retreatment was 12 months for the 51 patients receiving GKS compared with 6
      months for reoperation only (P = 0.001, hazard ratio [HR] 2.4), and 19 months
      versus 16 months from the time of primary diagnosis (P = 0.021, HR 1.8). A
      multivariate analysis adjusted for possible confounding factors (tumor volume,
      recursive partitioning analysis class, neurological deficits, time to recurrence,
      adjuvant therapy, and tumor location) showed significantly longer survival for
      patients treated with GKS, both from retreatment (P = 0.013, HR 4.1) and from
      primary diagnosis (P = 0.002, HR 5.8). The adjusted results were still
      significant after separate analysis according to tumor volume <5 mL, 5 to 20 mL,
      and >20 mL. The complications rate was 9.8% after GKS and 25.2% after
      reoperation. CONCLUSIONS: GKS may be an alternative to open surgery for small
      GBMs at the time of recurrences, with a significantly lower complication rate and
      a possible survival benefit compared with reoperation.

PMID- 22484079
TI  - Facilitation of memory by contextual cues in patients with diencephalic or medial
      temporal lobe dysfunction.
AB  - Item-context binding is crucial for successful episodic memory formation, and
      binding deficits have been suggested to underlie episodic-memory deficits. Here,
      our research investigated the facilitation of cued recall and recognition memory
      by contextual cues in 20 patients with Korsakoff's amnesia, 20 unilateral medial
      temporal lobectomy (MTL) patients and 36 healthy controls. In a computerized task
      participants had to learn 40 nouns that were randomly combined with a photograph
      of an everyday scene. Korsakoff patients showed a general memory deficit in both
      the cued recall and the recognition condition. A less severe memory impairment
      was found in the patients with medial-temporal lobectomy. Contextual cues
      facilitated cued recall to an equal extent in unilateral temporal lobectomy
      patients and healthy controls. However, no facilitation was observed in Korsakoff
      patients, suggesting an impairment in item-context binding during cued recall
      tasks. In contrast to the presumed exclusive dependency of recognition memory on
      item information, all groups equally profited from the contextual cues in
      recognition tasks. Our findings show that unilateral lesions as with MTL result
      in normal binding of context and item information, while bilateral dysfunction of
      the hippocampal-diencephalic system results in impaired context and item binding.

PMID- 22484080
TI  - The time course of neurolinguistic and neuropsychological symptoms in three cases
      of logopenic primary progressive aphasia.
AB  - Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting
      predominantly language abilities. Word-finding difficulties and comprehension
      deficits despite relatively preserved cognitive functions are characteristic
      symptoms during the first two years, and distinguish PPA from other dementia
      types like Alzheimer's disease. However, the dynamics of changes in language and
      non-linguistic abilities are not well understood. Most studies on progression
      used cross-sectional designs, which provide only limited insight into the course
      of the disease. Here we report the results of a longitudinal study in three cases
      of logopenic PPA over a period of 18 months, with exemplary longitudinal data
      from one patient even over 46 months. A comprehensive battery of neurolinguistic
      and neuropsychological tests was applied four times at intervals of six months.
      Over this period, deterioration of verbal abilities such as picture naming, story
      retelling, and semantic word recall was found, and the individual decline was
      quantified and compared between the three patients. Furthermore, decrease in non
      verbal skills such as divided attention and increasing apraxia was observed in
      all three patients. In addition, inter-subject variability in the progression
      with different focuses was observed, with one patient developing a non-fluent PPA
      variant. The longitudinal, multivariate investigation of logopenic PPA thus
      provides novel insights into the progressive deterioration of verbal as well as
      non-verbal abilities. These deficits may further interact and thus form a multi
      causal basis for the patients' problems in every-day life which need to be
      considered when planning individually targeted intervention in PPA.

PMID- 22484081
TI  - A novel, cost-effective and efficient chicken egg IgY purification procedure.
AB  - Chicken IgY antibodies have been touted to be a superior alternative to mammalian
      antibodies for use in various immunological, molecular biology and proteomics
      applications for several reasons. These include, but are not limited to, improved
      specificity due to maximum phylogenetic distance between host and recipient, cost
      effectiveness in maintaining commercial numbers of hens, IgY yield and the use of
      non-invasive methods used to isolate IgY from eggs as opposed to blood. Despite
      this, the routine use of IgY-based methodologies in the laboratory is not
      widespread. One reason for this reluctance may be derived from the difficulties
      and expense of isolating IgY antibodies from egg yolk in sufficient yield, with
      high purity at a realistic reasonable price. Here, we describe an extremely cost
      effective ($5USD per egg), rapid (within 5 h), efficient and optimised technique
      to isolate high yields (60 mg) of high purity (~80%) chicken IgY from egg yolks
      using the common plant gums pectin and kappa-carrageenan in the presence of
      calcium chloride to delipidate egg yolk mixtures whilst maintaining IgY in
      solution and then ammonium sulphate to subsequently precipitate the resulting IgY
      antibodies to higher purity. Our data demonstrates that this technique results in
      a high yield and purity of IgY that is comparable (if not superior to) existing
      commercial IgY isolation kits. The method also allows the isolation of
      immunologically active IgY which can be used for further downstream
      immunotechnological processes. Furthermore, it can also be easily implemented in
      a standard well equipped laboratory, and may be scaled up to commercial
      quantities (i.e., thousands of eggs).

PMID- 22484082
TI  - Promoting lower extremity strength in elite volleyball players: effects of two
      combined training methods.
AB  - OBJECTIVES: To compare the impact of short term training with resistance plus
      plyometric training (RT+P) or electromyostimulation plus plyometric training
      (EMS+P) on explosive force production in elite volleyball players. DESIGN:
      Sixteen elite volleyball players of the first German division participated in a
      training study. METHODS: The participants were randomly assigned to either the
      RT+P training group (n=8) or the EMS+P training group (n=8). Both groups
      participated in a 5-week lower extremity exercise program. Pre and post tests
      included squat jumps (SJ), countermovement jumps (CMJ), and drop jumps (DJ) on a
      force plate. The three-step reach height (RH) was assessed using a custom-made
      vertec apparatus. Fifteen m straight and lateral sprint (S15s and S15l) were
      assessed using photoelectric cells with interims at 5m and 10 m. RESULTS: RT+P
      training resulted in significant improvements in SJ (+2.3%) and RH (+0.4%)
      performance. The EMS+P training group showed significant increases in performance
      of CMJ (+3.8%), DJ (+6.4%), RH (+1.6%), S15l (-3.8%) and after 5m and 10 m of the
      S15s (-2.6%; -0.5%). The comparison of training-induced changes between the two
      intervention groups revealed significant differences for the SJ (p=0.023) in
      favor of RT+P and for the S15s after 5m (p=0.006) in favor of EMS+P. CONCLUSIONS:
      The results indicate that RT+P training is effective in promoting jump
      performances and EMS+P training increases jump, speed and agility performances of
      elite volleyball players.

PMID- 22484083
TI  - High serum Cu and Cu/Zn ratios correlate with impairments in bone density,
      physical performance and overall health in a population of elderly men with
      frailty characteristics.
AB  - Serum Cu levels rise with age and high Cu/Zn ratios are linked with multiple
      cause mortality in the elderly. The relationships of these parameters to measures
      of musculoskeletal health and frailty have not yet been analyzed. We used
      inductively coupled mass spectrometry to assess serum levels of Cu and Zn and
      probed for relationships between serum Cu levels and the Cu/Zn ratio with
      specific measures of bone, physical and overall health in a cohort of 144 frail
      elderly men. Subjects were divided into quintiles based on serum metal levels and
      comparisons for functional measures were made between the reference (middle)
      group and the low and high groups. Subjects' serum metal values were normally
      distributed. We found significant correlations between high Cu/Zn ratios and
      deficits in femoral bone mineral density, measures of speed and strength, muscle
      mass and hematocrit. High Cu/Zn ratios were also correlated with decreased
      triglycerides and increased reliance on ADL assistance. This study identifies
      specific deficits associated with high Cu/Zn ratios that span multiple organ
      systems and supports earlier studies indicating that serum Cu levels and the
      Cu/Zn ratio may serve as useful predictive biomarkers for poor health in the
      elderly.

PMID- 22484084
TI  - A novel disulfide-stabilized single-chain variable antibody fragment against
      rabies virus G protein with enhanced in vivo neutralizing potency.
AB  - Rabies is a fatal infectious disease requiring efficient protection provided by
      post-exposure prophylaxis (PEP) with rabies immunoglobulin (RIG). The single
      chain Fv fragment (scFv) is a small engineered antigen binding protein derived
      from antibody variable heavy (V(H)) and light (V(L)) chains. This novel antibody
      format may potentially replace the current application of RIG to detect and
      neutralize rabies virus (RV). However, the broad use of scFvs is confined by
      their generally low stability. In this study, a scFv (FV57) was constructed based
      on the monoclonal antibody, MAB57, against RV. To enhance its stability and
      neutralizing potency, a disulfide-stabilized scFv, ds-FV57, was also derived by
      introduction of cysteines at V(H)44 and V(L)100. Furthermore, the cysteine at
      V(L)85 of ds-FV57 was mutated to serine to construct ds-FV57(VL85Ser) in order to
      avoid potential mis-formed disulfide bonds which would alter the affinity of the
      scFv. The stability and activity of all three proteins expressed in Escherichia
      coli were evaluated. All of the constructed scFvs could provide efficient
      protection against RV infection both in vivo and in vitro. However, the stability
      of ds-FV57(VL85Ser) was notably improved, and its in vitro neutralizing potency
      against RV infection was enhanced. Our findings from these stabilization
      modifications support the feasibility of developing scFvs for PEP treatment of
      rabies.

PMID- 22484085
TI  - Morphology of Cambrian lobopodian eyes from the Chengjiang Lagerstatte and their
      evolutionary significance.
AB  - Visual organs are widely distributed throughout the animal kingdom and exhibit a
      great diversity of morphologies. Compound eyes consisting of numerous visual
      units (ommatidia) are the oldest preserved visual systems of arthropods, but
      their origins are obscure and hypothetical models for their evolution have been
      difficult to test in the absence of unequivocal fossil evidence. Here we reveal
      the detailed eye structures of well-preserved Early Cambrian lobopodians
      Luolishania longicruris and Hallucigenia fortis from the Chengjiang Lagerstatte,
      China. These animals possess a pair of eyes composed of at least two visual
      units, interpreted as pigment cups. Contrary to previous suggestions that
      Cambrian lobopodians possessed ocellus-like eyes comparable to those of extant
      onychophorans, this multi-component structure is more similar to the lateral eyes
      of arthropods. Morphological comparison and phylogenetic analyses indicate that
      these lobopodian eyes may represent an early stage in the evolution of the
      ancestral visual system of euarthropods.

PMID- 22484086
TI  - Core genome conservation of Staphylococcus haemolyticus limits sequence based
      population structure analysis.
AB  - The notoriously multi-resistant Staphylococcus haemolyticus is an emerging
      pathogen causing serious infections in immunocompromised patients. Defining the
      population structure is important to detect outbreaks and spread of antimicrobial
      resistant clones. Currently, the standard typing technique is pulsed-field gel
      electrophoresis (PFGE). In this study we describe novel molecular typing schemes
      for S. haemolyticus using multi locus sequence typing (MLST) and multi locus
      variable number of tandem repeats (VNTR) analysis. Seven housekeeping genes
      (MLST) and five VNTR loci (MLVF) were selected for the novel typing schemes. A
      panel of 45 human and veterinary S. haemolyticus isolates was investigated. The
      collection had diverse PFGE patterns (38 PFGE types) and was sampled over a 20
      year-period from eight countries. MLST resolved 17 sequence types (Simpsons index
      of diversity [SID]=0.877) and MLVF resolved 14 repeat types (SID=0.831). We found
      a low sequence diversity. Phylogenetic analysis clustered the isolates in three
      (MLST) and one (MLVF) clonal complexes, respectively. Taken together, neither the
      MLST nor the MLVF scheme was suitable to resolve the population structure of this
      S. haemolyticus collection. Future MLVF and MLST schemes will benefit from
      addition of more variable core genome sequences identified by comparing different
      fully sequenced S. haemolyticus genomes.

PMID- 22484087
TI  - Culture media for differential isolation of Lactobacillus casei Shirota from oral
      samples.
AB  - This study aimed to develop a solid culture medium for differential isolation of
      the probiotic strain Lactobacillus casei Shirota (LcS) and for selective
      cultivation of lactobacilli present in oral samples. Type strains of lactobacilli
      and isolates from commercial probiotic products were inoculated onto modified de
      Man Rogosa Sharpe agar (termed 'LcS Select'), containing bromophenol blue pH
      indicator, vancomycin and reducing agent L-cysteine hydrochloride for
      differential colony morphology development. L. casei Shirota cultured on the
      novel medium produced distinctive colony morphologies, different from other
      lactobacilli tested. LcS-characteristic colonies were recovered on LcS Select
      medium from samples of saliva and tongue plaque following a four-week probiotic
      intervention study. The viable count of presumptive LcS colonies correlated with
      those isolated on a non-commercial lactitol-LBS-vancomycin agar (LLV) developed
      for a selective isolation of LcS from faeces. The novel LcS Select medium proved
      suitable for differential isolation of the probiotic strain L. casei Shirota from
      oral samples containing mixed microbial populations. It can also be used for
      selective growth of vancomycin-resistant lactobacilli. There are few available
      culture media that are sufficiently selective to enable isolation of probiotic
      strains from mixed populations. LcS Select medium provides a cheaper, yet
      effective tool in this context.

PMID- 22484088
TI  - Validity of the Life Satisfaction questions, the Life Satisfaction Questionnaire,
      and the Satisfaction With Life Scale in persons with spinal cord injury.
AB  - OBJECTIVE: To assess and compare the validity of 3 life satisfaction instruments
      in persons with spinal cord injury (SCI). DESIGN: Cross-sectional study 5 years
      after discharge from inpatient rehabilitation. SETTING: Eight rehabilitation
      centers with specialized SCI units. PARTICIPANTS: Persons (N=225) with recently
      acquired SCI between 18 and 65 years of age were included in a cohort study. Data
      were available for 145 persons 5 years after discharge. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The Life Satisfaction questions (LS
      Questions), the Life Satisfaction Questionnaire (LiSat-9), and the Satisfaction
      With Life Scale (SWLS). RESULTS: There were no floor or ceiling effects. Cronbach
      alpha was questionable for the LS Questions (.60), satisfactory for the LiSat-9
      (.75), and good for the SWLS (.83). Concurrent validity was shown by strong and
      significant Spearman correlations (.59-.60) between all 3 life satisfaction
      instruments. Correlations with measures of mental health and participation were
      .52 to .56 for the LS Questions, .45 to .52 for the LiSat-9, and .41 to .48 for
      the SWLS. Divergent validity was shown by weak and in part nonsignificant
      correlations between the 3 life satisfaction measures and measures of functional
      independence and lesion characteristics. CONCLUSIONS: Overall, the validity of
      all 3 life satisfaction measures was supported. Despite questionable internal
      consistency, the concurrent and divergent validity of the LS Questions was at
      least as good as the validity of the LiSat-9 and the SWLS.

PMID- 22484089
TI  - Retrospective study of the effects of inpatient rehabilitation on improving and
      maintaining functional independence in people with Friedreich ataxia.
AB  - OBJECTIVES: To determine the effects of inpatient intervention for people with
      Friedreich ataxia (FRDA), and to identify whether improvements gained were
      sustained postdischarge. DESIGN: This retrospective observational cohort study
      comprised people with FRDA admitted to inpatient rehabilitation. SETTING: All
      participants in the study were referred by a specialist multidisciplinary FRDA
      clinic to inpatient rehabilitation. PARTICIPANTS: From 2003 until 2010, people
      (N=29; men, n=17; women, n=12) with FRDA were admitted to rehabilitation,
      representing 42 admissions. On admission, 9 participants were ambulant and 33
      participants were nonambulant. INTERVENTIONS: Each participant was prescribed
      goal-related therapy on an individual basis by the multidisciplinary team, and
      this consisted of a range of treatment approaches. MAIN OUTCOME MEASURE: The FIM
      was used to determine the efficacy of inpatient rehabilitation. RESULTS:
      Consistent with the progressive nature of the condition, FIM scores, as measured
      on an annual basis preintervention, declined over time. However, FIM scores
      increased by a mean of 8.5 points during periods of inpatient rehabilitation and
      continued to increase by a mean of 2.0 points during the period immediately after
      rehabilitation. Results demonstrate these increases during and immediately after
      inpatient rehabilitation were significant (P<.001). CONCLUSIONS: To the best of
      our knowledge, this study provides the first evidence that a period of inpatient
      rehabilitation reverses or halts the downward decline in function for people with
      FRDA. The benefits from this intervention continued during the period immediately
      after inpatient rehabilitation, indicating that these gains are more than just
      short-term achievements. Further exploration of intensity, type, and length of
      rehabilitation is required to ensure that the most appropriate rehabilitation is
      provided.

PMID- 22484090
TI  - Recombinant Brugia malayi pepsin inhibitor (rBm33) induced monocyte function and
      absence of apoptotic cell death: an in vitro study.
AB  - The effect of recombinant Brugia malayi pepsin inhibitor (rBm33) on human
      monocytes/macrophages has been examined using THP-1 cells. THP-1 cells stimulated
      with rBm33 showed enhanced levels of expression of pro-inflammatory cytokines (IL
      1beta, TNF-alpha, IL-6) and diminished levels of IL-12, iNOS and anti
      inflammatory cytokine (IL-10) expression suggesting the predominant features of
      Th1 response. Phorbol-12-myristate-13-acetate (PMA) treated THP-1 cells
      stimulated with rBm33 and subsequent incubation with GFP expressing Escherichia
      coli (E. coli) for 2 h enhanced the uptake of E. coli. Nitric oxide (NO) levels
      measured in the supernatants of these cultures did not show significant changes.
      Apoptotic studies with Peripheral Blood Mononuclear Cells (PBMCs) from normal
      individuals stimulated with rBm33 did not induce apoptosis of monocytes or
      lymphocytes. These observations suggest that rBm33 stimulates macrophages to
      induce Th1 response and does not promote apoptosis.

PMID- 22484092
TI  - Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and
      its constituents, safranal and crocin in allodynia and hyperalgesia induced by
      chronic constriction injury model of neuropathic pain in rats.
AB  - The current study was designed to evaluate therapeutic potential of systemically
      administered ethanolic and aqueous extracts of saffron as well as its bioactive
      ingredients, safranal and crocin, in chronic constriction injury (CCI)-induced
      neuropathic pain in rats. The von Frey filaments, acetone drop, and radiant heat
      test were performed to assess the degree of mechanical allodynia, thermal
      allodynia and thermal hyperalgesia respectively, at different time intervals,
      i.e., one day before surgery and 3, 5, 7 and 10 days post surgery. The ambulatory
      behavior was evaluated using the open field test. A 7-day treatment with the
      ethanolic and aqueous extracts (50,100 and 200 mg/kg, i.p.) and safranal (0.025,
      0.05 and 0.1 mg/kg, i.p.), attenuated the behavioral symptoms of neuropathic pain
      in a dose dependent manner. Crocin even at the high dose (50 mg/kg) failed to
      produce any protective role. However, gabapentine (100 mg/kg) as a reference drug
      significantly alleviated all behavioral manifestations of neuropathic pain
      compared to control group. In conclusion, the results of this study suggest that
      ethanolic and aqueous extracts of saffron as well as safranal could be useful in
      treatment of different kinds of neuropathic pains and as an adjuvant to
      conventional medicines.

PMID- 22484091
TI  - Two distinct binding modes define the interaction of Brox with the C-terminal
      tails of CHMP5 and CHMP4B.
AB  - Interactions of the CHMP protein carboxyl terminal tails with effector proteins
      play important roles in retroviral budding, cytokinesis, and multivesicular body
      biogenesis. Here we demonstrate that hydrophobic residues at the CHMP4B C
      terminal amphipathic alpha helix bind a concave surface of Brox, a mammalian
      paralog of Alix. Unexpectedly, CHMP5 was also found to bind Brox and specifically
      recruit endogenous Brox to detergent-resistant membrane fractions through its C
      terminal 20 residues. Instead of an alpha helix, the CHMP5 C-terminal tail adopts
      a tandem beta-hairpin structure that binds Brox at the same site as CHMP4B.
      Additional Brox:CHMP5 interface is furnished by a unique CHMP5 hydrophobic pocket
      engaging the Brox residue Y348 that is not conserved among the Bro1 domains. Our
      studies thus unveil a beta-hairpin conformation of the CHMP5 protein C-terminal
      tail, and provide insights into the overlapping but distinct binding profiles of
      ESCRT-III and the Bro1 domain proteins.

PMID- 22484093
TI  - Phenolics from Leontopodium leontopodioides inhibiting nitric oxide production.
AB  - Two new compounds, a neolignan (1), and a benzofuran derivative (2), along with 6
      known compounds (3-8), were isolated from the aerial parts of Leontopodium
      leontopodioides. The structures of the new compounds were elucidated as (7R,8S)
      3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol (1) and (2R)-12-hydoxy-4
      methoxy-tremeton (2) on the basis of their spectroscopic data, respectively. All
      of the isolates were evaluated for their effects on the inhibition of nitric
      oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophages and
      compounds 1 and 8 exhibited inhibitory activity with IC(50) values of 35.80 and
      24.41 MUM, respectively.

PMID- 22484094
TI  - Asymmetric dimethylarginine in adults with cystathionine beta-synthase
      deficiency.
AB  - In hyperhomocysteinemia (HHcy), an independent risk factor for cardiovascular
      diseases, endothelial dysfunction due to reduced bioavailability of nitric oxide
      is a consistent finding. However, the underlying mechanisms remain unknown.
      Increased levels of the nitric oxide synthase inhibitor asymmetric
      dimethylarginine (ADMA) have been associated with HHcy, and may contribute, at
      least in part, for the homocysteine-induced endothelial dysfunction, but whether
      cystathionine beta-synthase (CBS) deficiency is associated with increased ADMA
      has hardly been investigated. To address this question, we measured total
      homocysteine (tHcy), ADMA and symmetric dimethylarginine (SDMA) in plasma of 22
      adult CBS deficient patients, using established HPLC techniques. Results showed
      that in CBS deficient patients with elevated levels of tHcy (median (total
      range): 33 (14-237) MUmol/L), both ADMA and SDMA levels were normal. Moreover,
      tHcy and ADMA concentrations were not correlated (r(s)=0.017, p=0.94). Our
      results favor the hypothesis that the negative vascular effects of HHcy have an
      ADMA-independent etiology.

PMID- 22484096
TI  - Ribosome-inactivating proteins: current status and biomedical applications.
AB  - Ribosome-inactivating proteins (RIPs) are mainly present in plants and function
      to inhibit protein synthesis through the removal of adenine residues from
      eukaryotic ribosomal RNA (rRNA). They are broadly classified into two groups:
      type I and type II. Type I RIPs are a diverse family of proteins comprising a
      single polypeptide chain, whereas type II RIPs are heterodimeric glycoproteins
      comprising an A-chain (functionally equivalent to a type I RIP) linked via a
      disulphide bond to a B chain, mediating cell entry. In this review, we describe
      common type I and type II RIPs, their diverse biological functions, mechanism of
      cell entry, stability in plasma and antigenicity. We end with a discussion of
      promising applications for RIPs in biomedicine.

PMID- 22484097
TI  - Walking the walk: the moderating role of proactive parenting on adolescents'
      value-congruent behaviors.
AB  - The current study longitudinally examined adolescents' internalization of values
      in four domains (drug use, prosocial, school, friends), and how these values were
      differentially related to behaviors (delinquency, prosocial behavior, school
      engagement, and deviant peer association) as a function of proactive parenting.
      Participants included 335 adolescents (M age of child at Time 2 = 12.28, SD =
      .99, 51% female) and their parents. Analyses examined associations between
      adolescents' values at Time 3 and corresponding behaviors at Time 4, and the
      moderating role of proactive parenting (assessed at Time 2 using cluster
      analysis). Results suggested that adolescents with the most consistent value
      congruent behavior had parents who used deference or reasoned deference as an
      approach to proactive parenting, highlighting the importance of autonomy
      supportive parenting in the encouragement of self-generated values and
      corresponding behaviors. Discussion focused on value-congruent behaviors and
      associations between values and behaviors across domains.

PMID- 22484098
TI  - The long and the short of it: the role of the zinc finger polyadenosine RNA
      binding protein, Nab2, in control of poly(A) tail length.
AB  - In eukaryotic cells, addition of poly(A) tails to transcripts by 3'-end
      processing/polyadenylation machinery is a critical step in gene expression. The
      length of the poly(A) tail influences the stability, nuclear export and
      translation of mRNA transcripts. Control of poly(A) tail length is thus an
      important mechanism to regulate the abundance and ultimate translation of
      transcripts. Understanding the global regulation of poly(A) tail length will
      require dissecting the contributions of enzymes, regulatory factors, and poly(A)
      binding proteins (Pabs) that all cooperate to regulate polyadenylation. A recent
      addition to the Pab family is the CCCH-type zinc finger class of Pabs that
      includes S. cerevisiae Nab2 and its human counterpart, ZC3H14. In S. cerevisiae,
      Nab2 is an essential nuclear Pab implicated in both poly(A) RNA export from the
      nucleus and control of poly(A) tail length. Consistent with an important role in
      regulation of poly(A) tail length, depletion of Nab2 from yeast cells results in
      hyperadenylation of poly(A) RNA. In this review, we focus on the role of Nab2 in
      poly(A) tail length control and speculate on potential mechanisms by which Nab2
      could regulate poly(A) tail length based on reported physical and genetic
      interactions. We present models, illustrating how Nab2 could regulate poly(A)
      tail length by limiting polyadenylation and/or enhancing trimming. Given that
      mutation of the gene encoding the human Nab2 homologue, ZC3H14, causes a form of
      autosomal recessive intellectual disability, we also speculate on how mutations
      in a gene encoding a ubiquitously expressed Pab lead specifically to neurological
      defects. This article is part of a Special Issue entitled: Nuclear Transport and
      RNA Processing.

PMID- 22484100
TI  - Attenuated Wnt/beta-catenin signalling mediates methotrexate chemotherapy-induced
      bone loss and marrow adiposity in rats.
AB  - Cancer chemotherapy often causes significant bone loss, marrow adiposity and
      haematopoietic defects, yet the underlying mechanisms and recovery potential
      remain unclear. Wnt/beta-catenin signalling is integral to the regulation of
      osteogenesis, adipogenesis and haematopoiesis; using a rat model, the current
      study investigated roles of this signalling pathway in changes to bone marrow
      stromal and haematopoietic cell differentiation after chemotherapy with
      methotrexate (MTX), a commonly used antimetabolite. MTX treatment in rats (5
      daily administrations at 0.75 mg/kg) has previously been found to decrease bone
      volume and increase marrow fat, which was associated with increased
      osteoclastogenesis in haematopoietic cells and with an osteogenesis to
      adipogenesis switch in bone marrow stromal cells of treated rats. In the current
      study, on day 6 after the first MTX dose we found that accompanying these changes
      as well as a suppressed haematopoietic cellularity but increased
      granulocyte/macrophage differentiation potential, there was an increase in mRNA
      expression of Wnt antagonists sFRP-1 and Dkk-1 in bone, a reduction in nuclear
      beta-catenin protein in bone marrow stromal cells, and decreased mRNA levels of
      beta-catenin target genes lef-1, cyclin D1 and survivin, suggesting reduced
      activation of Wnt/beta-catenin signalling in the bone during MTX-induced damage.
      Concurrent administration of BIO, a GSK-3beta inhibitor that stabilises beta
      catenin, partially abrogated the MTX-induced transient changes in
      osteogenic/adipogenic commitment, granulocyte/macrophage lineage differentiation
      and osteoclast number. These findings demonstrate a potentially important role of
      Wnt/beta-catenin signalling in MTX chemotherapy-induced cellular changes to the
      bone marrow microenvironment.

PMID- 22484101
TI  - A novel splint for proximal interphalangeal joint contractures: a case report.
AB  - Proximal interphalangeal (PIP) joint contractures are notoriously difficult to
      treat. Best results are obtained with early mobilization and splinting, though a
      high level of adherence is critical for a good outcome. A new roll-on splint that
      aims to increase motion with minimal difficulty was used. The patient described
      here with moderate PIP joint contractures (30 degrees -60 degrees ) was treated
      successfully using this splint. The splint design and therapy protocol are
      described. The patient was treated for 12 weeks with good adherence to therapy
      and splinting. Total active motion increased by 87% in the index finger and 108%
      in the ring finger. Grip, pinch, and tip-pinch strengths increased. The
      Disabilities of the Arm, Shoulder and Hand score improved from 26.7% to 2.5%. At
      3 months, the patient returned to work. Though this case illustrates some of the
      advantages and disadvantages of the new splint, further study is necessary to
      evaluate the splint and compare it with other existing forms of treatment for PIP
      joint contractures.

PMID- 22484099
TI  - Complex dynamics of transcription regulation.
AB  - Transcription is a tightly regulated cellular function which can be triggered by
      endogenous (intrinsic) or exogenous (extrinsic) signals. The development of novel
      techniques to examine the dynamic behavior of transcription factors and the
      analysis of transcriptional activity at the single cell level with increased
      temporal resolution has revealed unexpected elements of stochasticity and
      dynamics of this process. Emerging research reveals a complex picture, wherein a
      wide range of time scales and temporal transcription patterns overlap to generate
      transcriptional programs. The challenge now is to develop a perspective that can
      guide us to common underlying mechanisms, and consolidate these findings. Here we
      review the recent literature on temporal dynamics and stochastic gene regulation
      patterns governed by intrinsic or extrinsic signals, utilizing the glucocorticoid
      receptor (GR)-mediated transcriptional model to illustrate commonality of these
      emerging concepts. This article is part of a Special Issue entitled: Chromatin in
      time and space.

PMID- 22484102
TI  - An automated methodology for levodopa-induced dyskinesia: assessment based on
      gyroscope and accelerometer signals.
AB  - OBJECTIVE: In this study, a methodology is presented for an automated levodopa
      induced dyskinesia (LID) assessment in patients suffering from Parkinson's
      disease (PD) under real-life conditions. METHODS AND MATERIAL: The methodology is
      based on the analysis of signals recorded from several accelerometers and
      gyroscopes, which are placed on the subjects' body while they were performing a
      series of standardised motor tasks as well as voluntary movements. Sixteen
      subjects were enrolled in the study. The recordings were analysed in order to
      extract several features and, based on these features, a classification technique
      was used for LID assessment, i.e. detection of LID symptoms and classification of
      their severity. RESULTS: The results were compared with the clinical annotation
      of the signals, provided by two expert neurologists. The analysis was performed
      related to the number and topology of sensors used; several different
      experimental settings were evaluated while a 10-fold stratified cross validation
      technique was employed in all cases. Moreover, several different classification
      techniques were examined. The ability of the methodology to be generalised was
      also evaluated using leave-one-patient-out cross validation. The sensitivity and
      positive predictive values (average for all LID severities) were 80.35% and
      76.84%, respectively. CONCLUSIONS: The proposed methodology can be applied in
      real-life conditions since it can perform LID assessment in recordings which
      include various PD symptoms (such as tremor, dyskinesia and freezing of gait) of
      several motor tasks and random voluntary movements.

PMID- 22484103
TI  - [Development of integrated support software for drug validation].
AB  - OBJECTIVE: To describe the development of a tool to automate detection of adverse
      drug-related events (ADRE) in all patients in a hospital. METHOD: We selected the
      ADRE that we wished to detect (administering drugs to patients with kidney
      failure and/or by enteral feeding tube) We designed software to record, process
      and integrate analytical results from SELENE((r)) clinical history programme,
      treatment prescribed using Farmatools((r)), and the information included in the
      tables we designed. RESULTS: The programme allows us to automatically detect
      patients likely to experience the ADRE we defined, and recommends a modified
      treatment to the pharmacist. This new tool enables us to search for all patients
      who might have a specific ADRE. CONCLUSIONS: The software we designed may be a
      useful drug validation tool.

PMID- 22484104
TI  - [Osteomyelitis associated with Staphylococcus aureus infection and reduced
      susceptibility to vancomycin treated with daptomycin].

PMID- 22484105
TI  - [Severe hypernatraemia after hypertonic sodium chloride use in hepatic
      hydatidosis surgery].

PMID- 22484106
TI  - Review of hypersensitivity reactions to antineoplastic agents.
AB  - OBJECTIVE: To review the characteristics and management of hypersensitivity
      reactions caused by antineoplastic agents. METHOD: We conducted a search in the
      Pubmed and EMBASE databases for the last 10 years. RESULTS: Almost all
      chemotherapeutic agents have the potential to cause hypersensitivity reactions,
      but some groups have been associated with increased risk, such as platinum
      compounds, taxanes, asparaginase, monoclonal antibodies and epipodophyllotoxins.
      The clinical manifestations of these reactions are variable and unpredictable,
      including symptoms affecting the skin and the pulmonary, cardiac and
      gastrointestinal systems. The mechanism associated with their development is not
      yet fully understood. Diagnosis is based on patients' signs and symptoms and skin
      testing. The management of patients who suffer a hypersensitivity reaction to a
      chemotherapeutic agent varies with the severity of the reaction, the need to
      continue treatment, and the availability of alternative therapies. CONCLUSIONS:
      Due to a progressive increase in the use of chemotherapeutic agents an increased
      incidence of hypersensitivity reactions is to be expected. Desensitisation
      protocols are a noteworthy alternative that make it possible to re-initiate
      patients' therapy with the causative agent of the hypersensitivity reaction.
      Their use should be assessed individually, weighing risks and benefits.

PMID- 22484107
TI  - In silico identification of potential antigenic proteins and promiscuous CTL
      epitopes in Mycobacterium tuberculosis.
AB  - Cell-mediated immunity is critical for the control of Mycobacterium tuberculosis
      infection. We hypothesized that those proteins of M. tuberculosis (MTB) that do
      not have homologs in humans as well as human gut flora, would mount a good
      antigenic response in man, and employed a bioinformatics approach to identify MTB
      antigens capable of inducing a robust cell-mediated immune response in humans. In
      the first step we identified 624 MTB proteins that had no homologs in humans.
      Comparison of this set of proteins with the proteome of 77 different microbes
      that comprise the human gut flora narrowed down the list to 180 proteins unique
      to MTB. Twenty nine of the 180 proteins are known to be associated with dormancy.
      Since dormancy associated proteins are known to harbor CTL epitopes, we selected
      four representative unique proteins and subjected them to epitope analysis using
      ProPred1. Nineteen novel promiscuous epitopes were identified in the four
      proteins. Population coverage for 7 of the 19 shortlisted epitopes including
      Rv3852 (58-KPAEAPVSL, 112-VPLIVAVTL, 118-VTLSLLALL and 123-LALLLIRQL), Rv2706c
      (66-RPLSGVSFL) Rv3466 (8- RIVEVFDAL and 38-RSLERLECL) was >74%. These novel
      promiscuous epitopes are conserved in other virulent MTB strains, and can
      therefore be further investigated for their immunological relevance and
      usefulness as vaccine candidates.

PMID- 22484108
TI  - First clonal spread of KPC-producing Pseudomonas aeruginosa in Buenos Aires,
      Argentina.

PMID- 22484109
TI  - Improved signal peptide predictions in mycobacteria?

PMID- 22484110
TI  - Biological correlates and predictors of insulin resistance among early
      adolescents.
AB  - Abnormal glucose metabolism is associated with obesity, insulin resistance (IR),
      and Type 2 diabetes mellitus. The purposes of this study were to describe
      anthropometric and laboratory markers of adolescents, examine correlates of IR,
      and test ability of anthropometric and laboratory markers to predict risk of
      exhibiting IR. A total of 150 early adolescents participated. Participants with
      obesity had increased IR, high-sensitivity C-reactive protein, triglycerides, and
      blood pressure. Waist circumference and triglycerides were predictive of IR.
      Multiple risk factors compound and lead to long-term health consequences among
      youth. Nurses can evaluate these factors to identify IR.

PMID- 22484111
TI  - Central kappa opioid receptors modulate salt appetite in rats.
AB  - The role of the central opioid system in the control of water and salt intake is
      complex, with both stimulatory and inhibitory effects having been observed. The
      aim of the present study was to investigate the participation of the central
      kappa-opioid receptors in the control of salt appetite. Male Wistar rats were
      submitted to two different experimental protocols: sodium deficit produced by the
      diuretic, furosemide, and brain angiotensinergic stimulation in rats under normal
      sodium balance. Lateral ventricle (LV) injections of Nor-binaltorphimine (Nor
      BNI) at different doses (5, 10 and 20 nmol) inhibited hypertonic saline solution
      (1.5%) intake in sodium-depleted rats. The salt appetite induced by an LV
      injection of angiotensin II (Ang II) (10 ng) was also blocked by Nor-BNI
      injections into the LV, while no significant change was observed in water intake.
      Furthermore, the decrease in salt intake seems not to have been due to a general
      inhibition of locomotor activity or to any change in palatability, since central
      administration of Nor-BNI failed to modify the intake of a 0.1% saccharin
      solution when the animals were submitted to a "dessert test" or to induce any
      significant locomotor deficit in the open-field test. Also the central
      administration of Nor-BNI was unable to modify blood pressure in sodium-depleted
      animals. The present results suggest that activation of endogenous kappa-opioid
      receptors modulates salt appetite induced by sodium depletion and by central
      angiotensinergic stimulation in rats.

PMID- 22484113
TI  - Effects of early life interventions and palatable diet on anxiety and on
      oxidative stress in young rats.
AB  - Early life events can change biochemical, endocrine and behavioral aspects
      throughout the life of an animal. Since there is a strong relationship between
      stress, neonatal handling and feeding behavior, the aim of this study was to
      investigate the effects of these three factors on behavioral parameters (anxiety
      and locomotion), oxidative stress in brain structures (prefrontal cortex and
      hippocampus) and on plasma glucose. Nests of Wistar rats were handled (10
      min/day), or not (control groups), on days 1-10 after birth. Males from these
      groups were divided into 4 subgroups: (1) stressed by isolation in childhood (pre
      puberty) and with access to a highly palatable diet (2) stressed by isolation and
      receiving standard lab chow (3) not isolated and receiving a highly palatable
      diet and (4) not isolated and receiving standard chow. The animals were kept
      under these conditions for 7 days. Rats receiving the highly palatable diet
      consumed more food, more calories, gained more weight and had a higher plasma
      glucose level, but had a lower caloric efficiency than the standard chow groups.
      Both handling and palatable diet were able to increase food consumption on the
      first day of isolation. Isolation stress had an anxiogenic effect in the plus
      maze, which was counteracted by handling. Palatable diet increased time spent in
      the central area of the open field apparatus and in the open arms of the elevated
      plus maze, showing an anxiolytic effect. The use of both these conditions,
      however, does not appear to bring additional protection against the effects of
      stress during this particular period of life, i.e., pre-puberty. In the
      prefrontal cortex, handling reduced thiol content and appears to imbalance the
      antioxidant enzymes system, which is counteracted by a palatable diet.
      Hippocampus seems to be more sensitive than the prefrontal cortex to early
      interventions, especially to the highly palatable diet, and both handling and
      diet appear to imbalance the antioxidant enzyme system. Thus, measurements of
      antioxidant enzymes activities indicate that handling may endanger some brain
      structures and that the palatable diet was able to prevent some handling effects
      on antioxidant enzymes, depending on the brain structure.

PMID- 22484114
TI  - Construction of a long hairpin RNA expression library using Cre recombinase.
AB  - A large number of genome-wide screens using RNA interference (RNAi) libraries
      have been utilized to determine the function of individual gene products involved
      in a variety of biological processes. In this study, we describe a new method to
      enzymatically generate a long hairpin RNA (lhRNA) expression library from a cDNA
      plasmid library using a nicking endonuclease, BcaBEST DNA polymerase, and Cre
      recombinase without excising the inserted DNA fragment from the plasmid vector.
      This method involves 5 steps: (1) conversion of an inserted DNA fragment in a
      plasmid into a direct repeat (DR); (2) purification of the plasmid containing the
      DR; (3) subcloning a lox71 cassette into the plasmid; (4) conversion of the DR in
      the plasmid into an inverted repeat (IR) using Cre recombinase; and (5)
      purification of the plasmid containing the IR. We also established an efficient
      method for inserting DNase I-digested DNA fragments into expression plasmids to
      enable construction of a cDNA plasmid library suitable as source materials to
      construct the lhRNA expression library. We confirmed that each of the lhRNA
      expression plasmids constructed using this method induced strong RNAi in a
      silkworm cell line, NIAS-Bm-oyanagi2.

PMID- 22484115
TI  - Carbohydrate synthesis and biosynthesis technologies for cracking of the glycan
      code: recent advances.
AB  - The glycan code of glycoproteins can be conceptually defined at molecular level
      by the sequence of well characterized glycans attached to evolutionarily
      predetermined amino acids along the polypeptide chain. Functional consequences of
      protein glycosylation are numerous, and include a hierarchy of properties from
      general physicochemical characteristics such as solubility, stability and
      protection of the polypeptide from the environment up to specific glycan
      interactions. Definition of the glycan code for glycoproteins has been so far
      hampered by the lack of chemically defined glycoprotein glycoforms that proved to
      be extremely difficult to purify from natural sources, and the total chemical
      synthesis of which has been hitherto possible only for very small molecular
      species. This review summarizes the recent progress in chemical and
      chemoenzymatic synthesis of complex glycans and their protein conjugates.
      Progress in our understanding of the ways in which a particular glycoprotein
      glycoform gives rise to a unique set of functional properties is now having far
      reaching implications for the biotechnology of important glycodrugs such as
      therapeutical monoclonal antibodies, glycoprotein hormones, carbohydrate
      conjugates used for vaccination and other practically important protein
      carbohydrate conjugates.

PMID- 22484112
TI  - An animal model of panic vulnerability with chronic disinhibition of the
      dorsomedial/perifornical hypothalamus.
AB  - Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility
      to induction of panic attacks by subthreshold interoceptive stimuli such as
      sodium lactate infusions or hypercapnia induction. Here we review a model of
      panic vulnerability in rats involving chronic inhibition of GABAergic tone in the
      dorsomedial/perifornical hypothalamic (DMH/PeF) region that produces enhanced
      anxiety and freezing responses in fearful situations, as well as a vulnerability
      to displaying acute panic-like increases in cardioexcitation, respiration
      activity and "flight" associated behavior following subthreshold interoceptive
      stimuli that do not elicit panic responses in control rats. This model of panic
      vulnerability was developed over 15 years ago and has provided an excellent
      preclinical model with robust face, predictive and construct validity. The model
      recapitulates many of the phenotypic features of panic attacks associated with
      human panic disorder (face validity) including greater sensitivity to panicogenic
      stimuli demonstrated by sudden onset of anxiety and autonomic activation
      following an administration of a sub-threshold (i.e., do not usually induce panic
      in healthy subjects) stimulus such as sodium lactate, CO(2), or yohimbine. The
      construct validity is supported by several key findings; DMH/PeF neurons regulate
      behavioral and autonomic components of a normal adaptive panic response, as well
      as being implicated in eliciting panic-like responses in humans. Additionally,
      patients with PD have deficits in central GABA activity and pharmacological
      restoration of central GABA activity prevents panic attacks, consistent with this
      model. The model's predictive validity is demonstrated by not only showing panic
      responses to several panic-inducing agents that elicit panic in patients with PD,
      but also by the positive therapeutic responses to clinically used agents such as
      alprazolam and antidepressants that attenuate panic attacks in patients. More
      importantly, this model has been utilized to discover novel drugs such as group
      II metabotropic glutamate agonists and a new class of translocator protein
      enhancers of GABA, both of which subsequently showed anti-panic properties in
      clinical trials. All of these data suggest that this preparation provides a
      strong preclinical model of some forms of human panic disorders.

PMID- 22484116
TI  - Risk of corticosteroid-induced hyperglycemia requiring medical therapy among
      patients with inflammatory eye diseases.
AB  - OBJECTIVE: To identify the incidence and risk factors for corticosteroid-induced
      hyperglycemia requiring medical therapy among patients with inflammatory eye
      diseases. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with ocular
      inflammation followed at 5 United States tertiary centers that initially were
      neither diabetic nor taking hypoglycemic medications. METHODS: Eligible patients
      who used oral corticosteroids during follow-up were identified and followed
      longitudinally for initiation of hypoglycemic medication over 1 year after
      beginning corticosteroids. The remaining eligible patients were followed for 1
      year after their initial visit. Survival analysis was used to calculate the risk
      of hyperglycemia requiring medical therapy and to identify potential risk
      factors. MAIN OUTCOME MEASURES: Initiation of hypoglycemic medications. RESULTS:
      Among 2073 non-diabetic patients treated with oral corticosteroids, 25 (1.21%)
      initiated hypoglycemic therapy compared with 5 of 2666 patients (0.19%) not
      treated with oral corticosteroids (relative risk [RR], 4.39; 95% confidence
      interval [CI], 1.68-11.5). The RR tended to be higher in association with higher
      initial doses (for initial doses <40 mg of prednisone per day: RR, 3.23; 95% CI,
      1.08-9.64; for initial prednisone dose >=40 mg/d: RR, 5.51; 95% CI, 2.01-15.1).
      Other risk factors for the initiation of hypoglycemic therapy included older age
      (RR [per each additional 10 years], 1.46; 95% CI, 1.15-1.85; P = 0.002) and
      African-American race (RR, 2.94; 95% CI, 1.34-6.43; P = 0.007). CONCLUSIONS:
      These results suggest that the absolute risk of corticosteroid-induced
      hyperglycemia that is detected and treated with hypoglycemic therapy in the
      tertiary ocular inflammation setting is low (an excess cumulative risk on the
      order of 1% within 1 year), although on a relative scale it is approximately 4.4
      fold higher than in patients not treated with oral corticosteroids. Older age and
      African-American race also were risk factors. Physicians who use systemic
      corticosteroids for ocular inflammatory diseases should be aware of this risk,
      and should consider surveillance for hyperglycemia among high-risk patients.
      However, given the low absolute risk, routine laboratory monitoring or referral
      for monitoring may not be necessary for low-risk patients.

PMID- 22484117
TI  - Neuroimaging in patients referred to a neuro-ophthalmology service: the rates of
      appropriateness and concordance in interpretation.
AB  - OBJECTIVE: Neuroimaging studies frequently are ordered to investigate neuro
      ophthalmic symptoms. When misused, these studies are expensive and time
      consuming. This study describes the type and frequency of neuroimaging errors in
      patients referred to an academic neuro-ophthalmology service and measures how
      frequently these neuroimaging studies were reinterpreted. DESIGN: Prospective
      cohort study. PARTICIPANTS: Eighty-four consecutive patients referred to an
      academic neuro-ophthalmology practice. METHODS: From November 2009 through July
      2010, 84 consecutive new patients who had undergone a neuroimaging study in the
      last 12 months specifically to evaluate their presenting neuro-ophthalmic
      symptoms were enrolled prospectively. Participants then underwent a complete
      neuro-ophthalmic evaluation, followed by a review of prior neuroimaging.
      Questions regarding appropriateness of the most recent imaging, concordance of
      radiologic interpretation, and re-evaluation of referring diagnoses were answered
      by the attending physician. MAIN OUTCOME MEASURES: The frequency and types of
      errors committed in the use of neuroimaging and the frequency of reinterpretation
      of prereferral neuroimaging studies after neuro-ophthalmic history and
      examination. RESULTS: Most study participants (84.5%; 71/84) underwent magnetic
      resonance imaging before referral; 15.5% (13/84) underwent only computed
      tomography. The rate of suboptimal neuroimaging studies was 38.1% (32/84). The 3
      most common reasons for suboptimal studies were incomplete area of imaging
      (34.4%; 11/32), wrong study type (28.1%; 9/32), and poor image quality (21.9%;
      7/32). Twenty-four of 84 subjects (28.6%) required additional neuroimaging. The
      authors agreed with the radiology interpretation of the prior neuroimaging
      studies in most patients (77.4%; 65/84). The most common anatomic locations for
      discordance in interpretation were the intraorbital optic nerve (35%; 7/20) and
      the brainstem (20%; 4/20). CONCLUSIONS: There was a high rate of suboptimal
      neuroimaging studies performed in patients referred for neuro-ophthalmology
      examination. These findings have significant implications given the increasing
      attention to resource use currently and in the near future.

PMID- 22484118
TI  - Efficacy of 5-day levofloxacin-containing concomitant therapy in eradication of
      Helicobacter pylori infection.
AB  - BACKGROUND & AIMS: Helicobacter pylori have become resistant to antimicrobial
      agents, reducing eradication rates. A 10-day sequential regimen that contains
      levofloxacin was efficient, safe, and cost saving in eradicating H pylori
      infection in an area with high prevalence of clarithromycin resistance. We
      performed a noninferiority randomized trial to determine whether a 5-day
      levofloxacin-containing quadruple concomitant regimen was as safe and effective
      as the 10-day sequential regimen in eradicating H pylori in previously untreated
      patients. METHODS: We randomly assigned patients with H pylori infection to
      groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice
      daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and
      tinidazole 500 mg twice daily; n = 90) or 10 days of sequential therapy
      (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed
      by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and
      tinidazole 500 mg twice daily for 5 more days; n = 90). Antimicrobial resistance
      was assessed by the E-test. Efficacy, adverse events, and costs were determined.
      RESULTS: Intention-to-treat analysis showed similar eradication rates for
      concomitant (92.2%; 95% confidence interval [CI], 84.0%-95.8%) and sequential
      therapies (93.3%; 95% CI, 86.9%-97.3%). Per-protocol eradication results were
      96.5% (95% CI, 91%-99%) for concomitant therapy and 95.5% for sequential therapy
      (95% CI, 89.6%-98.5%). The differences between sequential and concomitant
      treatments were 1.1% in the intention-to-treat study (95% CI; -7.6% to 9.8%) and 
      1.0% in the per-protocol analysis (95% CI; -8.0% to 5.9%). The prevalence of
      antimicrobial resistance and incidence of adverse events were comparable between
      groups. Concomitant therapy cost $9 less than sequential therapy. CONCLUSIONS:
      Five days of levofloxacin-containing quadruple concomitant therapy is as
      effective and safe, and less expensive, in eradicating H pylori infection than 10
      days of levofloxacin-containing sequential therapy.

PMID- 22484119
TI  - Interleukin-22 promotes proliferation of liver stem/progenitor cells in mice and
      patients with chronic hepatitis B virus infection.
AB  - BACKGROUND & AIMS: Proliferation of liver stem/progenitor cells (LPCs), which can
      differentiate into hepatocytes or biliary epithelial cells, is often observed in
      chronically inflamed regions of liver in patients. We investigated how
      inflammation might promote proliferation of LPCs. METHODS: We examined the role
      of interleukin (IL)-22, a survival factor for hepatocytes, on proliferation of
      LPCs in patients with chronic hepatitis B virus (HBV) infection and in mice.
      Proliferation of LPCs in mice was induced by feeding a diet that contained 3,5
      diethoxycarbonyl-1,4-dihydrocollidine (DDC). RESULTS: Hepatic expression of IL-22
      was increased in patients with HBV and correlated with the grade of inflammation
      and proliferation of LPCs. Mice on the DDC diet that overexpressed an IL-22
      transgene specifically in liver (IL-22TG), or that were infected with an IL-22
      expressing adenovirus, had increased proliferation of LPCs. Signal transducer and
      activator of transcription (STAT) 3, a component of the IL-22 signaling pathway,
      was activated in LPCs isolated from DDC-fed IL-22TG mice. Deletion of STAT3 from
      livers of IL-22TG mice reduced proliferation of LPCs. In addition, the receptors
      IL-22R1 and IL-10R2 were detected on epithelial cell adhesion molecule(+)CD45(-)
      LPCs isolated from DDC-fed wild-type mice. Culture of these cells with IL-22
      activated STAT3 and led to cell proliferation, but IL-22 had no effect on
      proliferation of STAT3-deficient EpCAM(+)CD45(-) LPCs. IL-22 also activated STAT3
      and promoted proliferation of cultured BMOL cells (a mouse LPC line).
      CONCLUSIONS: In livers of mice and patients with chronic HBV infection,
      inflammatory cells produce IL-22, which promotes proliferation of LPCs via STAT3.
      These findings link inflammation with proliferation of LPCs in patients with HBV
      infection.

PMID- 22484121
TI  - A new reversed-phase/strong anion-exchange mixed-mode stationary phase based on
      polar-copolymerized approach and its application in the enrichment of
      aristolochic acids.
AB  - A novel silica-based reversed-phase/strong anion-exchange mixed-mode stationary
      phase named C18SAX was synthesized based on the polar-copolymerized approach.
      C18SAX stationary phase showed excellent compatibility with 100% aqueous mobile
      phase and comparable performance with commercial SunFireTM C18 column in terms of
      column efficiency and methylene selectivity. And the results indicated that
      hydrophobic interaction and anion-exchange mechanism dominate the separation
      process of aristolochic acids. The utility of C18SAX material-based SPE was
      demonstrated for the enrichment of aristolochic acids extracted from Caulis
      Aristochiae Manshuriensis. The SPE method was developed rapidly and simply by
      HPLC evaluation. Under the optimized SPE conditions, the average recoveries of
      aristolochic acid I and aristolochic acid II in crude sample were 72.36% and
      105.59%, with RSDs of 5.77% and 1.13%, respectively. The complexity of sample
      matrices was significantly simplified after the SPE procedure and further
      preparation and purification of target compounds was performed on a preparative
      C18TDE column. Four aristolochic acids, including aristolochic acid I (31.8 mg),
      II (8.9 mg), IIIa (6.1 mg) and IVa (4.3 mg) were purified with HPLC purities all
      above 93%. The results proved that the aristolochic acids could be efficiently
      enriched by C18SAX material and easily eluted in acidic conditions, indicating
      its great potential in the enrichment of acidic compounds from complex matrices.

PMID- 22484120
TI  - MicroRNA-26a promotes cholangiocarcinoma growth by activating beta-catenin.
AB  - BACKGROUND & AIMS: MicroRNAs (miRNAs) have been implicated in the development and
      progression of human cancers. We investigated the roles and mechanisms of miR-26a
      in human cholangiocarcinoma. METHODS: We used in situ hybridization and
      quantitative reverse transcriptase polymerase chain reaction to measure
      expression of miR-26a in human cholangiocarcinoma tissues and cell lines (eg,
      CCLP1, SG231, HuCCT1, TFK1). Human cholangiocarcinoma cell lines were transduced
      with lentiviruses that expressed miR-26a1 or a scrambled sequence (control);
      proliferation and colony formation were analyzed. We analyzed growth of human
      cholangiocarcinoma cells that overexpress miR-26a or its inhibitor in severe
      combined immune-deficient mice. Immunoblot, immunoprecipitation, DNA pull-down,
      immunofluorescence, and luciferase reporter assays were used to measure
      expression and activity of glycogen synthase kinase (GSK)-3beta, beta-catenin,
      and related signaling molecules. RESULTS: Human cholangiocarcinoma tissues and
      cell lines had increased levels of miR-26a compared with the noncancerous biliary
      epithelial cells. Overexpression of miR-26a increased proliferation of
      cholangiocarcinoma cells and colony formation in vitro, whereas miR-26 depletion
      reduced these parameters. In severe combined immune-deficient mice,
      overexpression of miR-26a by cholangiocarcinoma cells increased tumor growth and
      overexpression of the miR-26a inhibitor reduced it. GSK-3beta messenger RNA was
      identified as a direct target of miR-26a by computational analysis and
      experimental assays. miR-26a-mediated reduction of GSK-3beta resulted in
      activation of beta-catenin and induction of several downstream genes including c
      Myc, cyclinD1, and peroxisome proliferator-activated receptor delta. Depletion of
      beta-catenin partially prevented miR-26a-induced tumor cell proliferation and
      colony formation. CONCLUSIONS: miR-26a promotes cholangiocarcinoma growth by
      inhibition of GSK-3beta and subsequent activation of beta-catenin. These
      signaling molecules might be targets for prevention or treatment of
      cholangiocarcinoma.

PMID- 22484122
TI  - Selective transport of single protein molecules inside gold nanotubes.
AB  - Diffusion of single protein molecules inside gold nanotubes was investigated. 3
      dimensional imaging was employed to locate the individual molecules inside the
      nanotubes as a function of time. As expected, larger proteins and smaller pore
      sizes resulted in smaller diffusion coefficients. Diffusion within PEG-coated
      gold nanotubes was found to be two orders of magnitude faster than in previously
      reported, similar sized untreated polycarbonate membrane pores, showing that
      adsorption was serious in the latter case. We further demonstrate chromatographic
      selectivity during transport by modifying the inner surface of the gold nanotubes
      with self-assembled monolayers of derivatized alkyl thiols. These results should
      be useful for designing membrane separations.

PMID- 22484123
TI  - Rapid control of Chinese star anise fruits and teas for neurotoxic anisatin by
      Direct Analysis in Real Time high resolution mass spectrometry.
AB  - After ingestion, products containing Chinese star anise (Illicium verum)
      contaminated or adulterated with Japanese star anise (Illicium anisatum) or other
      Illicium species, can cause epilepsy, hallucinations, and nausea due to the rare
      neurotoxic sesquiterpene dilactone anisatin that is present in Japanese star
      anise. Thus a rapid, simple and unambiguous method for distinguishing between the
      morphologically similar Chinese star anise and toxic Japanese star anise is
      important for food safety issues. Direct Analysis in Real Time (DART) ambient
      ionisation coupled with orbitrap high resolution mass spectrometry allowed the
      recording of mass spectra of anisatin in solid star anise fruits in seconds
      without any prior sample pretreatment. Spectra could be obtained in both positive
      ([M+NH(4)](+) at m/z 346.1496, C(15)H(24)NO(8)) and negative mode ([M-H](-) at
      m/z 327.1074, C(15)H(19)O(8)) and gave the same outcome provided a mass
      resolution of at least 27,000 is available. The anisatin signal was typically
      >1000 times larger in Japanese star anise than in Chinese star anise thus
      allowing an unequivocal qualitative determination. Herbal teas containing star
      anise fragments too small to be visually recognised, could be analysed by
      preparing a tea in 6 min and subsequently sampling ~2 MUL of tea on a glass rod.
      None of the 8 investigated retail teas contained significant quantities of
      anisatin. Spiking a complex herbal tea containing Chinese star anise with an
      equally concentrated tea prepared from Japanese star anise provided a linear
      calibration curve (R(2) >= 0.995) after normalising on a native constituent of
      Chinese star anise (standard addition method). This showed that adulteration down
      to 1% (w/w) is still measurable. Compared with existing PCR, TLC, GC-MS and HPLC
      ESI-MS/MS procedures, the proposed DART-HRMS procedure is faster and simpler and
      moreover measures the actual biotoxin.

PMID- 22484124
TI  - Application of CAD/CAM-assisted technique with surgical treatment in
      reconstruction of the mandible.
AB  - OBJECTIVE: The purpose of this clinical study was to explore the optimal method
      of reconstruct mandible defects individually and immediately. STUDY DESIGN: Three
      dimensional model simulation technique and vascularized fibular osteomyocutaneous
      flap were used to repair 15 cases of mandible defects, which were caused by
      ameloblastoma. A three-dimensional computed tomography (CT) images were converted
      to a virtual model using CAD software and the 3-dimensional (3D) simulated resin
      models of skeleton and fibula were used to design the osteotomies, bone segment
      replacement and titanium mesh shaping preoperatively. RESULTS: Fibula flaps were
      alive and no complication occurred. The patients were satisfied with the results
      both esthetically and functionally. CONCLUSIONS: This preliminarily clinical
      study and case demonstrated that CAD/CAM-assisted technique with surgical
      treatment offers an individual anatomical reconstruction of the mandible in
      ameloblastoma patients. The procedures guarantee intraoperatively an exact
      placement of the preformed mesh even for precise reconstruction of extensive
      mandible defects.

PMID- 22484125
TI  - Groningen temporomandibular total joint prosthesis: an 8-year longitudinal follow
      up on function and pain.
AB  - Total temporomandibular joint replacement is a surgical procedure for patients
      with severe temporomandibular joint afflictions affecting quality of life, which
      have not responded beneficially to previous conventional surgery. The aim of this
      study was to assess the long-term outcome of the Groningen temporomandibular
      joint (TMJ) prosthesis in patients with chronic pain and mutilated
      temporomandibular joints following multiple surgical procedures, with respect to
      prosthesis failure, the patient's postoperative level of satisfaction and
      longitudinal changes in maximum mouth opening, functional mandibular impairment
      and pain. Eight female patients were studied in whom Groningen TMJ prostheses
      were inserted, two unilaterally and six bilaterally. The Groningen TMJ prosthesis
      was mechanically successful during 8 years of follow-up in seven out of eight
      patients with a disc dislocation being seen in one patient (7%). Patients were
      satisfied, despite the limited improvement of the maximum mouth opening, and pain
      scores. Although the decline of MFIQ scores during 8 years of follow-up was
      significant compared to baseline (p=0.027), the effects of the prosthesis on
      maximum mouth opening, function and pain were limited. This may be due to
      persistent chronic pain and the adverse effects of multiple previous surgical
      procedures.

PMID- 22484126
TI  - Foam fractionation applications.
AB  - Biotechnological downstream processing faces several challenges, such as dilute
      product streams and contained target products which are sensitive to heat,
      oxidation, other chemicals, etc. State-of-the-art separation methods, e.g.
      chromatography, are not always the best option due to variable yield losses and
      high costs. Foam fractionation appears as a promising alternative unit operation
      in biotechnological downstream processing. From its applications in metal
      industry and on fish farms, it was developed further towards the recovery of
      phytonutrients, metabolites and proteins. However, no large scale applications of
      foam fractionation in biotechnological downstream processing exist yet. This is
      due to the complexity of various biotechnological media, which makes a
      universalized approach for systematic process design of protein separations
      difficult. Ongoing research in the fields of process engineering, surface
      chemistry and protein chemistry can help to close this gap. Although many
      different substances, such as detergents, have been separated or recovered using
      foam fractionation, this review focuses mainly on biotechnological applications,
      more specifically on protein separation.

PMID- 22484127
TI  - On-line multiple component analysis for efficient quantitative bioprocess
      development.
AB  - On-line monitoring devices for the precise determination of a multitude of
      components are a prerequisite for fast bioprocess quantification. On-line
      measured values have to be checked for quality and consistency, in order to
      extract quantitative information from these data. In the present study we
      characterized a novel on-line sampling and analysis device comprising an
      automatic photometric robot. We connected this on-line device to a bioreactor and
      concomitantly measured six components (i.e. glucose, glycerol, ethanol, acetate,
      phosphate and ammonium) during different batch cultivations of Pichia pastoris.
      The on-line measured data did not show significant deviations from off-line taken
      samples and were consequently used for incremental rate and yield calculations.
      In this respect we highlighted the importance of data quality and discussed the
      phenomenon of error propagation. On-line calculated rates and yields depicted the
      physiological responses of the P. pastoris cells in unlimited and limited
      cultures. A more detailed analysis of the physiological state was possible by
      considering the off-line determined biomass dry weight and the calculation of
      specific rates. Here we present a novel device for on-line monitoring of
      bioprocesses, which ensures high data quality in real-time and therefore refers
      to a valuable tool for Process Analytical Technology (PAT).

PMID- 22484128
TI  - A transcriptional study of acidogenic chemostat cells of Clostridium
      acetobutylicum--cellular behavior in adaptation to n-butanol.
AB  - To gain more insight into the butanol stress response of Clostridium
      acetobutylicum the transcriptional response of a steady state acidogenic culture
      to different levels of n-butanol (0.25-1%) was investigated. No effect was
      observed on the fermentation pattern and expression of typical solvent genes
      (aad, ctfA/B, adc, bdhA/B, ptb, buk). Elevated levels of butanol mainly affected
      class I heat-shock genes (hrcA, grpE, dnaK, dnaJ, groES, groEL, hsp90), which
      were upregulated in a dose- and time-dependent manner, and genes encoding
      proteins involved in the membrane composition (fab and fad or glycerophospholipid
      related genes) and various ABC-transporters of unknown specificity.
      Interestingly, fab and fad genes were embedded in a large, entirely repressed
      cluster (CAC1988-CAC2019), which inter alia encoded an iron-specific ABC
      transporter and molybdenum-cofactor synthesis proteins. Of the
      glycerophospholipid metabolism, the glycerol-3-phosphate dehydrogenase (glpA)
      gene was highly upregulated, whereas a glycerophosphodiester ABC-transporter
      (ugpAEBC) and a phosphodiesterase (ugpC) were repressed. On the megaplasmid, only
      a few genes showed differential expression, e.g. a rare lipoprotein (CAP0058,
      repressed) and a membrane protein (CAP0102, upregulated) gene. Observed
      transcriptional responses suggest that C. acetobutylicum reacts to butanol stress
      by induction of the general stress response and changing its cell envelope and
      transporter composition, but leaving the central catabolism unaffected.

PMID- 22484129
TI  - Schistocephalus solidus infections increase gonadotropins and gonadotropin
      releasing hormone (GnRH3) mRNA levels in the three-spined stickleback,
      Gasterosteus aculeatus.
AB  - Parasites often impair the reproduction of their hosts, one well known case being
      the cestode Schistocephalus solidus which is a common parasite in three-spined
      sticklebacks, Gasterosteus aculeatus. One of the possible ways that this could be
      exerted is by suppression on the brain-pituitary-gonadal (BPG) axis. In this
      study, mRNA levels of FSH-beta and LH-beta and of GnRH2 (cGnRH II) and GnRH3
      (sGnRH) were measured via Q-PCR in infected and uninfected fish sampled from the
      field a few weeks before the onset of breeding. The pituitary mRNA levels of both
      FSH-beta and LH-beta were higher in infected males than in uninfected males. Also
      in females, FSH-beta mRNA levels were higher in infected individuals than in
      others, whereas there was no significant difference found in LH-beta expression.
      Brain mRNA levels of GnRH3 were higher in infected fish than in uninfected fish
      in both sexes, but no difference was found in GnRH2 mRNA levels. Thus, infection
      by S. solidus was able to alter the expressions not only of gonadotropins (GtHs),
      but also of GnRH which has not been observed previously. However, the effects are
      opposite to what should be expected if the parasite suppressed reproduction via
      actions on the brain-pituitary level. The gonads are perhaps more likely to be
      impaired by the parasites in other ways, and changed feedbacks on the BPG axis
      could then lead to the increases in GtHs and GnRH.

PMID- 22484130
TI  - Characterization of thioredoxin glutathione reductase in Schiotosoma japonicum.
AB  - Schistosomiasis is one of the most prevalent and serious parasitic diseases in
      the world and remains an important public health problem in China. Screening and
      discovery of an effective vaccine candidate or new drug target is crucial for the
      control of this disease. In this study, we cloned a cDNA encoding Schistosoma
      japonicum (S. japonicum) thioredoxin glutathione reductase (SjTGR) from the cDNA
      of 42-day-old adult worms. The open reading frame (ORF) of the gene was 1791 base
      pairs (bp) encoding a protein of 596 amino acids. SjTGR was subcloned into pET
      32a (+) and expressed in Escherichia coli (E. coli) BL21 (DE3). The recombinant
      protein rSjTGR exhibited enzymatic activity of 5.13U/mg with DTNB as the
      substrate, and showed strong immunogenecity. Real-time PCR results indicated that
      SjTGR was expressed at a higher level in 35-day-old schistosome worms in
      transcript. We vaccinated BALB/c mice with rSjTGR in combination with MONTANIDETM
      ISA 206 VG (ISA 206) and observed a 33.50% to 36.51% (P<0.01) decrease in the
      adult worm burden and a 33.73%to 43.44% (P<0.01) decrease in the number of eggs
      counted compared to the ISA 206 or blank control groups in two independent
      vaccination tests. ELISA analysis demonstrated that rSjTGR induced a high level
      of SjTGR-specific IgG, IgG1, and IgG 2a antibodies and induced elevated
      production of IFN-gamma. This study provides the basis for further investigations
      into the biological function of SjTGR and further evaluation of the potential use
      of this molecule as a vaccine candidate or new drug target is warranted.

PMID- 22484131
TI  - Letter to the Editor regarding "Ovarian fluid plays an essential role in
      attachment of Eurasian perch, Perca fluviatilis eggs".

PMID- 22484133
TI  - Loss of malarial susceptibility to artemisinin in Thailand.

PMID- 22484134
TI  - Emergence of artemisinin-resistant malaria on the western border of Thailand: a
      longitudinal study.
AB  - BACKGROUND: Artemisinin-resistant falciparum malaria has arisen in western
      Cambodia. A concerted international effort is underway to contain artemisinin
      resistant Plasmodium falciparum, but containment strategies are dependent on
      whether resistance has emerged elsewhere. We aimed to establish whether
      artemisinin resistance has spread or emerged on the Thailand-Myanmar (Burma)
      border. METHODS: In malaria clinics located along the northwestern border of
      Thailand, we measured six hourly parasite counts in patients with uncomplicated
      hyperparasitaemic falciparum malaria (>=4% infected red blood cells) who had been
      given various oral artesunate-containing regimens since 2001. Parasite clearance
      half-lives were estimated and parasites were genotyped for 93 single nucleotide
      polymorphisms. FINDINGS: 3202 patients were studied between 2001 and 2010.
      Parasite clearance half-lives lengthened from a geometric mean of 2.6 h (95% CI
      2.5-2.7) in 2001, to 3.7 h (3.6-3.8) in 2010, compared with a mean of 5.5 h (5.2
      5.9) in 119 patients in western Cambodia measured between 2007 and 2010. The
      proportion of slow-clearing infections (half-life >=6.2 h) increased from 0.6% in
      2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and
      2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were
      identified, each of which infected between two and 13 patients. The proportion of
      variation in parasite clearance attributable to parasite genetics increased from
      30% between 2001 and 2004, to 66% between 2007 and 2010. INTERPRETATION:
      Genetically determined artemisinin resistance in P falciparum emerged along the
      Thailand-Myanmar border at least 8 years ago and has since increased
      substantially. At this rate of increase, resistance will reach rates reported in
      western Cambodia in 2-6 years. FUNDING: The Wellcome Trust and National
      Institutes of Health.

PMID- 22484135
TI  - How fat is fat?

PMID- 22484136
TI  - Excitation function for 7Be production in carbon by deuteron irradiations up to
      50 MeV.
AB  - In order to check and complement available experimental data for production of
      (7)Be in deuteron irradiation of (nat)C, new measurements with incident particle
      energy up to 50 MeV were performed. The (7)Be content, measured with HPGe
      spectroscopy, allows determination of the excitation function of the
      (nat)C(d,x)(7)Be reactions. A comparison with experimental literature values and
      results from updated theoretical codes (ALICE-D, EMPIRE-D, EAF2007 and TENDL2010
      on-line libraries) is discussed. Thick target yields were derived from fits to
      our cross-sections and integrated personnel dose was calculated for different
      irradiation cycles and exposure scenarios around the IFMIF facility.

PMID- 22484137
TI  - Determination of the energy response of closely tissue-equivalent diamond
      dosimeters for radiotherapy dosimetry.
AB  - A monoenergetic X-ray syncrotron source was used to determine the energy response
      of a diamond detector in the range 5-25 keV, clarifying the elemental composition
      of the detector. The response is shown to be influenced by the detector housing
      and electrical contacts. A model for the energy response of the detector is
      determined that is valid in the 5 keV-15 MeV with an accuracy of 5% and therefore
      can be used to correct the dosimeter response to low-energy and scattered
      radiation.

PMID- 22484138
TI  - Standardization of 125I and 109Cd by the photon-photon coincidence method in
      PTKMR-BATAN.
AB  - A photon-photon coincidence system was constructed for the standardization of
      (125)I and (109)Cd in PTKMR-BATAN, Indonesia. Two NaI(Tl) detectors of 76 mm
      diameter * 6mm thickness with 0.5mm aluminum window were used, which were
      positioned approximately symmetrically to the source holder. The electronic chain
      was almost the same as for a 4pibeta-gamma system. The CANBERRA Multiport II
      multi channel analyzer was used for energy calibration and a Philips type PM3092
      oscilloscope for visualization of the pulses. A polyethylene plastic was used as
      the source substrate for the (125)I and (109)Cd samples. The activity of a (125)I
      solution was measured by the photon-photon coincidence and the efficiency
      extrapolation method (Schrader and Walz, 1987), whereas the activity of a (109)Cd
      solution was determined by a tracer method using (125)I (Schrader, 2006). The
      result of the (125)I activity showed good agreement with the result of
      measurements using a calibrated ionization chamber, and the result of (109)Cd
      also showed good agreement with the measurements result using a LEGe detector.

PMID- 22484139
TI  - Airborne spectrometry: extraction of low energy gamma-rays using two or three
      spectral windows.
AB  - Airborne gamma-ray spectrometry with NaI(Tl) is a recognized tool for emergency
      mapping. The maps produced usually look for natural isotopes ((40)K, (238)U,
      (232)Th) and (137)Cs due to the Chernobyl accident. Nowadays a new thematic
      emerges as nuclear materials tracking. Such materials emitting at low energies
      require new algorithms and a new method is presented here based on counts
      observed in two or three spectral windows. Since altitude is an important factor
      to be taken into account, an improvement is proposed to follow flight altitude
      changes. An extension to medium energies is proposed and compared to windows
      methods and to peak detection.

PMID- 22484140
TI  - Dosimetric characteristics of jasper samples for high dose dosimetry.
AB  - Different colored jasper samples from Brazilian mines were powdered and mixed
      with teflon (composites jasper-teflonTM). This paper describes a preliminary
      study of a thermoluminescent method (TL) to verify the possibility of their use
      as high dose dosimeters or irradiation indicators in industrial areas. The jasper
      samples were exposed to different radiation doses, using the gamma-cell 220
      system (60Co) of IPEN. The TL emission curves of samples presented two peaks at
      130  degrees C and 190  degrees C. Calibration curves were obtained for the
      jasper samples between 50 Gy and 20 kGy. All five types of jasper samples showed
      their usefulness as irradiation indicators and as high-dose dosimeters.

PMID- 22484141
TI  - Differentiation in boron distribution in adult male and female rats' normal
      brain: a BNCT approach.
AB  - Boron distribution in adult male and female rats' normal brain after boron
      carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH:
      7.4) was studied in this research. Coronal sections of control and trial animal
      tissue samples were irradiated with thermal neutrons. Using alpha
      autoradiography, significant differences in boron concentration were seen in
      forebrain, midbrain and hindbrain sections of male and female animal groups with
      the highest value, four hours after boron compound injection.

PMID- 22484142
TI  - Standardization of 18F by digital coincidence counting.
AB  - The radioactivity of (18)F has been measured by a digital coincidence counting
      (DCC) system. The main advantages of the digital coincidence counting technique
      are a shortening of the measurement time as compared with conventional
      coincidence counting and an ability to obtain activities with various
      experimental parameters through off-line analysis. The measurement results of
      radioactivity for (18)F solution were compared with those of a conventional
      coincidence counting technique and a reference ion chamber method.

PMID- 22484143
TI  - Behavior and environmental impacts of radionuclides during the hydrometallurgy of
      calcareous and argillaceous rocks, southwestern Sinai, Egypt.
AB  - The hydrometallurgy of radionuclides means getting the radioelements from the
      rocks into solution by leaching, getting the radionuclides from the solution by
      extraction process, and then precipitation of the desired elements to obtain
      concentrate. The follow-up of the radionuclides during these processes is the
      main target of this work to identify the identity of the original samples,
      pregnant solutions (leachates), residuals and the concentrate. Six samples were
      chosen to achieve this work. The leaching process was carried out under the
      conditions; 20-30% acid (H(2)SO(4)) concentration, 1:3 solid/liquid ratios, 60
      min stirring time at room temperature. The activity concentrations of (238)U,
      (235)U, (234)U, (226)Ra, (214)Pb, (214)Bi, (232)Th and (40)K were measured in the
      original samples, residuals and U-concentrate (Bq/kg), and leachates (Bq/l). The
      results indicate that, the radionuclides before (226)Ra in the (238)U decay
      series are more leachable (released) than those from (226)Ra to (214)Bi in the
      order; (234)U>(238)U=(235)U >> (226)Ra>(214)Pb>(214)Bi. (232)Th and (40)K are
      immobile under the present conditions. The radiological hazards of natural
      radioactivity in the original samples, leachates, residuals and U-concentrate
      were calculated and compared with the internationally recommended values and were
      found to be much higher than the world average values.

PMID- 22484144
TI  - Evaluation of trace elements in some northern-Nigeria traditional medicinal
      plants using INAA technique.
AB  - Instrumental neutron activation analysis was used for multi-trace elemental
      determination of six medicinal plants: Boerhavia diffusa, Euphoria hirta, Senna
      occidentalis, Senna obtusofolia, Cyprus dilatatus and Mitracarpus villosu. These
      plants were irradiated in the Nigeria Research reactor-1, at flux levels of
      2.25E+11 ncm(-2)s(-1) in the outer channel and 5.0E+11 ncm(-2)s(-1) in the inner
      channel. A total of the twenty one elemental concentrations were evaluated
      highlighted the similarity between the elements obtained for the six plants. It
      was found that Euphoria hirta and Senna occidentalis have similar concentrations
      of elements. Boerhavia difusa, Mitracarpus villosus, Cyprus dilatalus and Senna
      obttusifolia were also similar in elemental content to each other, while
      Boerhavia difusa was the only exceptional outlier. The accuracy of measurements
      was evaluated by analyzing IAEA-359 cabbage references standard materials and the
      results show good agreement with certified or literature values within +/-0.01%
      to +/-0.87%.

PMID- 22484145
TI  - X-ray fluorescence analysis of archaeological finds and art objects: recognizing
      gold and gilding.
AB  - Many cultural heritage objects were gilded in the past, and nowadays they can be
      found in archeological excavations or in historical buildings dating back to the
      Middle Ages, or from the modern period. Old gilded artifacts have been studied
      using X-ray fluorescence analysis and 2D microanalysis. Several techniques that
      enable the user to distinguish gold and gilded objects are described and then
      applied to investigate artifacts. These techniques differ in instrumentation,
      data analysis and numbers of measurements. The application of Monte Carlo
      calculation to a quantitative analysis of gilded objects is also introduced.

PMID- 22484146
TI  - Sustained activation of AMPK ameliorates age-associated vascular endothelial
      dysfunction via a nitric oxide-independent mechanism.
AB  - Exercise restores endothelium-dependent dilation (EDD) in old mice by reducing
      oxidative stress and increasing nitric oxide (NO) bioavailability. Adenosine
      monophosphate protein kinase (AMPK) activation mimics some effects of exercise.
      Old (28-30 months) B6D2F1 mice had reduced arterial AMPK expression and
      superoxide-mediated suppression of EDD vs. young (3-6 months) controls.
      Pharmacological activation of AMPK by aminoimidazole carboxamide ribonucleotide
      (AICAR) for 2 weeks increased arterial AMPK and reversed this superoxide-induced
      impairment of EDD. The improvement in EDD was independent of NO or prostaglandin
      signaling, suggesting enhanced endothelium-dependent hyperpolarizing factor
      related dilation. AMPK activation may represent a novel therapy for treating age
      associated vascular dysfunction.

PMID- 22484147
TI  - Marine bromophenol bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, induces
      mitochondrial apoptosis in K562 cells and inhibits topoisomerase I in vitro.
AB  - Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a marine bromophenol
      compound derived from marine algae. Previous reports have shown that BDDE
      possesses cytotoxic activity. However, the mechanisms of its apoptotic activity
      as well as its potential cellular targets remain unclear. The present study
      demonstrated that BDDE displays broad-spectrum in vitro anticancer capabilities
      and exhibits potent apoptotic activity in K562 cells via mitochondrial pathway.
      Further study revealed that BDDE inhibits the activity of topoisomerase I but
      does not stimulate the formation of topoisomerase I-DNA complex nor intercalate
      into DNA. Ethidium bromide displacement fluorescence assay and molecular modeling
      results showed that BDDE mainly targets DNA and binds to DNA minor groove, and
      thereafter inhibits the activity of topoisomerase I. The results of this study
      indicated that BDDE, which has unique chemical structure different from current
      topoisomerase I inhibitors, could serve as a lead template for rational drug
      design and for future anticancer agents development.

PMID- 22484148
TI  - Cardiorespiratory fitness is negatively associated with metabolic risk factors
      independently of the adherence to a healthy dietary pattern.
AB  - BACKGROUND AND AIM: Cardiorespiratory fitness (CRF) and diet have been involved
      as significant factors towards the prevention of cardio-metabolic diseases. This
      study aimed to assess the impact of the combined associations of CRF and
      adherence to the Southern European Atlantic Diet (SEADiet) on the clustering of
      metabolic risk factors in adolescents. METHODS AND RESULTS: A cross-sectional
      school-based study was conducted on 468 adolescents aged 15-18, from the Azorean
      Islands, Portugal. We measured fasting glucose, insulin, total cholesterol (TC),
      HDL-cholesterol, triglycerides, systolic blood pressure, waits circumference and
      height. HOMA, TC/HDL-C ratio and waist-to-height ratio were calculated. For each
      of these variables, a Z-score was computed by age and sex. A metabolic risk score
      (MRS) was constructed by summing the Z scores of all individual risk factors.
      High risk was considered when the individual had >= 1 SD of this score. CRF was
      measured with the 20 m-Shuttle-Run-Test. Adherence to SEADiet was assessed with a
      semi-quantitative food frequency questionnaire. Logistic regression showed that,
      after adjusting for potential confounders, unfit adolescents with low adherence
      to SEADiet had the highest odds of having MRS (OR = 9.4; 95%CI:2.6-33.3) followed
      by the unfit ones with high adherence to the SEADiet (OR = 6.6; 95% CI: 1.9-22.5)
      when compared to those who were fit and had higher adherence to SEADiet.
      CONCLUSIONS: Unfit adolescents showed higher odds of having high MRS, regardless
      of the adherence to SEADiet suggesting that high CRF may overcome the deleterious
      effects of low adherence to a healthy dietary pattern in adolescents.

PMID- 22484149
TI  - Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced
      bioavailability in brain tissue for effective glioblastoma therapy.
AB  - Glioblastoma, the most aggressive form of brain and central nervous system
      tumours, is characterized by high rates proliferation, migration and invasion.
      The major road block in the delivery of drugs to the brain is the blood-brain
      barrier, along with the expression of various multi-drug resistance (MDR)
      proteins that cause the efflux of a wide range of chemotherapeutic drugs.
      Curcumin, a herbal drug, is known to inhibit cellular proliferation, migration
      and invasion and induce apoptosis of glioma cells. It also has the potential to
      modulate MDR in glioma cells. However, the greatest challenge in the
      administration of curcumin stems from its low bioavailability and high rate of
      metabolism. To circumvent the above pitfalls of curcumin we have developed
      curcumin-loaded glyceryl monooleate (GMO) nanoparticles (NP) coated with the
      surfactant Pluronic F-68 and vitamin E D-alpha-tocopheryl polyethylene glycol
      1000 succinate (TPGS) for brain delivery. We demonstrated that our curcumin
      loaded NPs inhibit cellular proliferation, migration and invasion along with a
      higher percentage of cell cycle arrest and telomerase inhibition, thus leading to
      a greater percentage apoptotic cell death in glioma cells compared with native
      curcumin. An in vivo study demonstrated enhanced bioavailability of curcumin in
      blood serum and brain tissue when delivered by curcumin-loaded GMO NPs compared
      with native curcumin in a rat model. Thus, curcumin-loaded GMO NPs can be used as
      an effective delivery system to overcome the challenges of drug delivery to the
      brain, providing a new approach to glioblastoma therapy.

PMID- 22484150
TI  - Effects of cryopreservation, decellularization and novel extracellular matrix
      conditioning on the quasi-static and time-dependent properties of the pulmonary
      valve leaflet.
AB  - Decellularized allografts offer potential as heart valve substitutes and
      scaffolds for cell seeding. The effects of decellularization on the quasi-static
      and time-dependent mechanical behavior of the pulmonary valve leaflet under
      biaxial loading conditions have not previously been reported in the literature.
      In the current study, the stress-strain, relaxation and creep behaviors of the
      ovine pulmonary valve leaflet were investigated under planar-biaxial loading
      conditions to determine the effects of decellularization and a novel post
      decellularization extracellular matrix (ECM) conditioning process. As expected,
      decellularization resulted in increased stretch along the loading axes. A
      reduction in relaxation was observed following decellularization. This was
      accompanied by a reduction in glycosaminoglycan (GAG) content. Based on previous
      implant studies, these changes may be of little functional consequence in the
      short term; however, the long term effects of decreased relaxation and GAG
      content remain unknown. Some restoration of relaxation was observed following ECM
      conditioning, especially in the circumferential specimen direction, which may
      help mitigate any detrimental effects due to decellularization. Regardless of
      processing, creep under biaxial loading was negligible.

PMID- 22484151
TI  - Docetaxel vs. vinorelbine in elderly patients with advanced non-small-cell lung
      cancer.

PMID- 22484152
TI  - Sindbis virus infectivity improves during the course of infection in both
      mammalian and mosquito cells.
AB  - Alphaviruses are enveloped, single-stranded positive sense RNA viruses that are
      transmitted by an arthropod vector to a wide host range, including avian and
      mammalian species. Arthropods and vertebrates have different cellular
      environments and this may cause the different cellular pathologies that are
      observed between the invertebrate vector and vertebrate hosts in both whole
      organisms and cultured cell lines. In this report, we used Sindbis virus and
      examined mosquito and mammalian cell lines for their ability to produce progeny
      virus particles. Total particles produced, viral titers, and overall infectivity
      (or the ratio of total particles-to-infectious particles) was investigated. Our
      results show (1) Sindbis infectivity is more a function of the host cell used in
      titering the virus rather than the cell line used to produce the virus, (2) the
      number of total and infectious particles produced is cell line dependent, and (3)
      the infectivity of released virus particles improves during the course of
      infection in both cells that have cytolytic infections and persistent infections.

PMID- 22484153
TI  - Biological characterization of non-steroidal progestins from botanicals used for
      women's health.
AB  - Progesterone plays a central role in women's reproductive health. Synthetic
      progestins, such as medroxyprogesterone acetate (MPA) are often used in hormone
      replacement therapy (HRT), oral contraceptives, and for the treatment of
      endometriosis and infertility. Although MPA is clinically effective, it also
      promiscuously binds to androgen and glucocorticoid receptors (AR/GR) leading to
      many undesirable side effects including cardiovascular diseases and breast
      cancers. Therefore, identifying alternative progestins is clinically significant.
      The purpose of this study was to biologically characterize non-steroidal
      progestins from botanicals by investigating theirinteraction and activation of
      progesterone receptor (PR). Eight botanicals commonly used to alleviate
      menopausal symptoms were investigated to determine if they contain progestins
      using a progesterone responsive element (PRE) luciferase reporter assay and a PR
      polarization competitive binding assay. Red clover extract stimulated PRE
      luciferase and bound to PR. A library of purified compounds previously isolated
      from red clover was screened using the luciferase reporter assay. Kaempferol
      identified in red clover and a structurally similar flavonoid, apigenin, bound to
      PR and induced progestegenic activity and P4 regulated genes in breast epithelial
      cells and human endometrial stromal cells (HESC). Kaempferol and apigenin
      demonstrated higher progestegenic potency in the HESC compared to breast
      epithelial cells. Furthermore, phytoprogestins were able to activate P4 signaling
      in breast epithelial cells without downregulating PR expression. These data
      suggest that botanical extracts used for women's health may contain compounds
      capable of activating progesterone receptor signaling.

PMID- 22484154
TI  - The regulatory tandem domains of human phosphodiesterases 1 and 4 regulate a
      cyanobacterial adenylyl cyclase.
AB  - Human phosphodiesterase 1 is regulated by a tandem of N-terminal
      calmodulin/Ca(2+)-binding domains. We grafted the tandems from hPDE1A3 and -B1
      onto the cyanobacterial adenylyl cyclase CyaB1 thus replacing an intrinsic tandem
      GAF-domain. Cyclase activity was stimulated by Ca(2+)/calmodulin 1.9 to 4.4-fold,
      i.e. similarly as reported for hPDE1 regulation. hPDE4 long isoforms are
      activated by phosphorylation of a serine located in a conserved RRESF motif in a
      tandem of N-terminal upstream-conserved regions (UCR). We grafted the UCR tandems
      from hPDE4A4, -B1, and -D3 onto the CyaB1 cyclase as a reporter enzyme. Activity
      was enhanced 1.4 to 4.5-fold by respective phosphomimetic (S/D) point mutations.
      Similarly, cyclase activity was increased 2.5-fold by phosphorylation of the
      chimera with the PDE4D3 UCR tandem by cAMP-dependent protein kinase. We propose a
      common mechanism of activation in mammalian phosphodiesterases containing N
      terminal tandem regulatory domains. A downstream region is suggested to alternate
      between random and ordered conformations and to enable switching between
      inactive, the catalytic domain occluding PDE homodimers and active monomeric PDE
      catalytic domains.

PMID- 22484156
TI  - Possible mechanisms underlying the biphasic regulatory effects of arachidonic
      acid on Ca2+ signaling in HEK293 cells.
AB  - Arachidonic acid (AA), an endogenous lipid signal molecule released from membrane
      upon cell activation, modulates intracellular Ca(2+) ([Ca(2+)](i)) signaling
      positively and negatively. However, the mechanisms underlying the biphasic
      effects of AA are rather obscure. Using probes for measurements of [Ca(2+)](i)
      and fluidity of plasma membrane (PM)/endoplasmic reticulum (ER), immunostaining,
      immunoblotting and shRNA interference approaches, we found that AA at low
      concentration, 3 MUM, reduced the PM fluidity by activating PKCalpha and
      PKCbetaII translocation to PM and also the ER fluidity directly. In accordance, 3
      MUM AA did not impact the basal [Ca(2+)](i) but significantly suppressed the
      thapsigargin-induced Ca(2+) release and Ca(2+) influx. Inhibition of PKC with
      Go6983 or knockdown of PKCalpha or PKCbeta using shRNA significantly attenuated
      the inhibitory effects of 3 MUM AA on PM fluidity and agonist-induced Ca(2+)
      signal. However, AA at high concentration, 30 MUM, caused robust release and
      entry of Ca(2+) accompanied by a facilitated PM fluidity but decreased ER
      fluidity and dramatic PKCbetaI and PKCbetaII redistribution in the ER. Compared
      with ursodeoxycholate acid, a membrane stabilizing agent that only inhibited the
      30 MUM AA-induced Ca(2+) influx by 45%, Gd(3+) at concentration of 10 MUM could
      completely abolish both release and entry of Ca(2+) induced by AA, suggesting
      that the potentiated PM fluidity is not the only reason for AA eliciting Ca(2+)
      signal. Therefore, the study herein demonstrates that a lowered PM fluidity by
      PKC activation and a direct ER stabilization contribute significantly for AA
      downregulation of [Ca(2+)](i) response, while Gd(3+)-sensitive 'pores' in PM/ER
      play an important role in AA-induced Ca(2+) signal in HEK293 cells.

PMID- 22484157
TI  - Extrapolating respiratory tract infection incidences to a rural area of Ghana
      using a probability model for hospital attendance.
AB  - OBJECTIVE: The aim of the current study was to extrapolate incidences for
      respiratory tract infections (RTI) using referral data from a local hospital in
      Ghana weighted by the individual likelihood of a hospital visit. METHODS:
      Diagnoses from children visiting a rural hospital in Ghana during August 2007 to
      September 2008 were recorded. A logistic regression model, based on a population
      study conducted within the hospital catchment area, was used to calculate the
      individual probability of clinic attendance and to extrapolate the number of
      recorded cases. Cumulative incidences for children living in the hospital
      catchment area were estimated. RESULTS: Upper RTI was the most common respiratory
      diagnosis, with an extrapolated incidence of 17481 cases per 100000 per year,
      followed by pneumonia with an incidence of 2496 per 100 000 per year. All
      diseases analyzed were most common in the first year of life. CONCLUSIONS: In
      general the study results are in line with comparable studies. Several
      methodological issues biasing the results in different directions were
      identified. For example, opportunistic infections that are more often observed in
      hospital attendees are likely to be overestimated. However, the applied approach
      presents a tool for areas where disease monitoring systems are not established.

PMID- 22484155
TI  - Myocyte enhancer factor 2 (MEF2) tethering to muscle selective A-kinase anchoring
      protein (mAKAP) is necessary for myogenic differentiation.
AB  - Differentiation of skeletal myoblast cells to functional myotubes involves highly
      regulated transcriptional dynamics. The myocyte enhancer factor 2 (MEF2)
      transcription factors are critical to this process, synergizing with the master
      regulator MyoD to promote muscle specific gene transcription. MEF2 is extensively
      regulated by myogenic stimuli, both transcriptionally and post-translationally,
      but to date there has been little progress in understanding how signals upstream
      of MEF2 are coordinated to produce a coherent response. In this study, we define
      a novel interaction between the muscle A-kinase anchoring protein (mAKAP) and
      MEF2 in skeletal muscle. Discrete domains of MEF2 and mAKAP bind directly. Their
      interaction was exploited to probe the function of mAKAP-tethered MEF2 during
      myogenic differentiation. Dominant interference of MEF2/mAKAP binding was
      sufficient to block MEF2 activation during the early stages of differentiation.
      Furthermore, extended expression of this disrupting domain effectively blocked
      myogenic differentiation, halting the formation of myotubes and decreasing
      expression of several differentiation markers. This study expands our
      understanding of the regulation of MEF2 in skeletal muscle and identifies the
      mAKAP scaffold as a facilitator of MEF2 transcription and myogenic
      differentiation.

PMID- 22484158
TI  - Hepatoprotective effect of lucidone against alcohol-induced oxidative stress in
      human hepatic HepG2 cells through the up-regulation of HO-1/Nrf-2 antioxidant
      genes.
AB  - Lucidone was previously reported to exhibit anti-inflammatory activity in vitro
      and in vivo. In the present study, we characterized the mechanisms underlying the
      hepatoprotective effect of lucidone against alcohol-induced oxidative stress in
      vitro. Human hepatoma (HepG2) cells were pretreated with lucidone (1-10MUg/mL)
      and then hepatotoxicity was stimulated by the addition ethanol (100mM). With
      response to ethanol-challenge, increased amount of alanine aminotransferase (ALT)
      and aspirate aminotransferase (AST) release were observed, whereas lucidone
      pretreatment significantly inhibited the leakage of AST and ALT in HepG2 cells
      without appreciable cytotoxic effects. We also found that lucidone pretreatment
      significantly decreased ethanol-induced nitric oxide (NO), tumor necrosis factor
      alpha (TNF-alpha), malondialdehyde (MDA), reactive oxygen species (ROS) and
      glutathione (GSH) depletion in HepG2 cells. Furthermore, Western blot and
      quantitative-PCR analyses showed that ethanol-exposure apparently down-regulated
      endogenous anti-oxidant hemoxygenase-1 (HO-1) expression, whereas pretreatment
      with lucidone significantly up-regulates HO-1 expression followed by the
      transcriptional activation of NF-E2 related factor-2 (Nrf-2). Interestingly, the
      profound up-regulation of HO-1 and Nrf-2 were observed in only ethanol-challenged
      cells, which evidenced that lucidone-induced induction of HO-/Nrf-2 were specific
      with oxidative stress. Thus, we concluded that lucidone-mediated up-regulation of
      phase-II enzymes and HO-1 via Nrf-2 signaling pathway may provide a pivotal
      mechanism for its hepatoprotective action.

PMID- 22484159
TI  - Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro
      and in vivo approaches.
AB  - The present study was conducted to determine whether exposure to the mono-(2
      ethylhexyl) phthalate (MEHP) represents a genuine threat to male human
      reproductive function. To this aim, we investigated the effects on human male
      fetal germ cells of a 10-5 M exposure. This dose is slightly above the mean
      concentrations found in human fetal cord blood samples by biomonitoring studies.
      The in vitro experimental approach was further validated for phthalate toxicity
      assessment by comparing the effects of in vitro and in vivo exposure in mouse
      testes. Human fetal testes were recovered during the first trimester (7-12 weeks)
      of gestation and cultured in the presence or not of 10-5 M MEHP for three days.
      Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ
      cells. The concentration of phthalate reaching the fetal gonads was determined by
      radioactivity measurements, after incubations with 14C-MEHP. A 10-5 M exposure
      significantly increased the rate of apoptosis in human male fetal germ cells. The
      intratesticular MEHP concentration measured corresponded to the concentration
      added in vitro to the culture medium. Furthermore, a comparable effect on germ
      cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This
      study suggests that this 10-5 M exposure is sufficient to induce changes to the
      in vivo development of the human fetal male germ cells.

PMID- 22484160
TI  - Human and animal health risk assessments of chemicals in the food chain:
      comparative aspects and future perspectives.
AB  - Chemicals from anthropogenic and natural origins enter animal feed, human food
      and water either as undesirable contaminants or as part of the components of a
      diet. Over the last five decades, considerable efforts and progress to develop
      methodologies to protect humans and animals against potential risks associated
      with exposure to such potentially toxic chemicals have been made. This special
      issue presents relevant methodological developments and examples of risk
      assessments of undesirable substances in the food chain integrating the animal
      health and the human health perspective and refers to recent Opinions of the
      Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food
      Safety Authority (EFSA). This introductory review aims to give a comparative
      account of the risk assessment steps used in human health and animal health risk
      assessments for chemicals in the food chain and provides a critical view of the
      data gaps and future perspectives for this cross-disciplinary field.

PMID- 22484161
TI  - In vitro antioxidant activity and in vivo antidepressant-like effect of alpha
      (phenylselanyl) acetophenone in mice.
AB  - In this study, the antioxidant and antidepressant-like effects of alpha
      (phenylselanyl) acetophenone (PSAP), an organoselenium compound, were
      investigated. To assess the in vitro antioxidant properties, PSAP was evaluated
      in four test systems (DPPH, ABTS, FRAP and inhibition of lipid peroxidation).
      PSAP (100-500 MUM) showed potent antioxidant activity and protected against lipid
      peroxidation. Additionally, we investigated whether PSAP, when administered in
      mice (100, 200 and 400mg/kg, per oral, p.o.), could cause acute toxicity. Our
      results demonstrated that PSAP did not cause the death of any animal,
      significantly reduce body weight or cause any oxidative tissue stress following
      treatment. This study also evaluated the effect of PSAP (0.1-10 mg/kg, p.o) on
      mice in a forced swim test (FST) and tail suspension test (TST), assays that are
      predictive of depressant activity and motor activity in the open-field. PSAP (5
      10 mg/kg) significantly reduced immobility time in the FST and TST without
      affecting motor activity. In addition, the antidepressant-like effect caused by
      PSAP (5m/kg, p.o) in mice during the TST was dependent on an interaction with the
      serotonergic system (5-HT(1A) receptors), but not with the noradrenergic,
      dopaminergic or adenosinergic system. Together, these results suggest that PSAP
      possesses antioxidant and antidepressant-like properties and may be of interest
      as a therapeutic agent for the treatment of depressive disorders.

PMID- 22484162
TI  - Why don't intensive care nurses perform routine delirium assessment? A discussion
      of the literature.
AB  - Delirium is a well recognised and serious problem in adult intensive care
      patients. With a reported incidence as high as 87%, it has been associated with
      increased length of stay, higher costs of care, ongoing cognitive impairment and
      increased mortality rates. The problem is so significant that routine, formal
      delirium assessment is recommended for all intensive care patients. However,
      there is evidence to suggest that few intensive care nurses are incorporating
      this screening into their daily practice. The aim of this paper is to discuss
      what is currently known about intensive care nurses' attitudes and beliefs in
      relation to caring for adults who are experiencing delirium, with a focus on
      identifying possible barriers to formal delirium assessment. It will be argued
      that intensive care nurses are well placed to perform regular delirium assessment
      and therefore have a responsibility to promote an improvement in delirium
      assessment practices.

PMID- 22484163
TI  - Purification and characterization of a trehalase-invertase enzyme with dual
      activity from Candida utilis.
AB  - Trehalose and sucrose, two important anti-stress non-reducing natural
      disaccharides, are catabolized by two enzymes, namely trehalase and invertase
      respectively. In this study, a 175 kDa enzyme protein active against both
      substrates was purified from wild type Candida utilis and characterized in
      detail. Substrate specificity assay and activity staining revealed the enzyme to
      be specific for both sucrose and trehalose. The ratio between trehalase and
      invertase activity was found to be constant at 1:3.5 throughout the entire study.
      Almost 40-fold purification and 30% yield for both activities were achieved at
      the final step of purification. The presence of common enzyme inhibitors, thermal
      and pH stress had analogous effects on its trehalase and invertase activity. Km
      values for two activities were similar while Vmax and Kcat also differed by a
      factor of 3.5. Competition plot for both substrates revealed the two activities
      to be occurring at the single active site. N-terminal sequencing and MALDI-TOF
      data analysis revealed higher similarity of the purified protein to previously
      known neutral trehalases. While earlier workers mentioned independent
      purification of neutral trehalase or invertase from different sources, the
      present study reports the purification of a single protein showing dual activity.

PMID- 22484164
TI  - Flow (shear stress)-mediated remodeling of resistance arteries in diabetes.
AB  - Shear stress due to blood flow is the most important force stimulating vascular
      endothelium. Acute stimulation of the endothelium by shear stress induces a
      vasodilatation mainly due to the release of nitric oxide (NO) among other
      relaxing agents. After a chronic increase in blood flow (shear stress), the
      endothelium triggers diameter enlargement, medial hypertrophy and improvement of
      arterial contractility and endothelium-mediated dilation. Shear stress-mediated
      outward remodeling requires an initial inflammatory response followed by the
      production of reactive oxygen species (ROS) and peroxinitrite anions, which
      activate MMPs and extracellular matrix digestion allowing diameter expansion.
      This outward remodeling occurs in collateral growth following occlusion of a
      large artery. In diabetes, an excessive ROS production is associated with the
      formation of advanced glycation end-products (AGEs) and the glycation of enzymes
      involved in vascular tone. The balance between inflammation, AGEs and ROS level
      determines the ability of resistance arteries to develop outward remodeling
      whereas AGEs and ROS contribute to decrease endothelium-mediated dilation in
      remodeled vessels. This review explores the interaction between ROS, AGEs and the
      endothelium in shear stress-mediated outward remodeling of resistance arteries in
      diabetes. Restoring or maintaining this remodeling is essential for an efficient
      blood flow in distal organs.

PMID- 22484165
TI  - Coloring-decoloring behavior of amphiphilic fluoroalkyl end-capped N-(1,1
      dimethyl-3-oxobutyl)acrylamide--acryloylmorpholine cooligomer/fluorescein
      nanocomposites in protic and aprotic solvents.
AB  - Amphiphilic fluoroalkyl end-capped N-(1,1-dimethyl-3-oxobutyl)acrylamide
      acryloylmorpholine cooligomer/fluorescein nanocomposites afforded brilliant
      yellow-colored solutions in not only protic solvents such as methanol and ethanol
      but also protic-like solvents such as dichloromethane and 1,2-dichloroethane,
      respectively. However, the corresponding non-fluorinated cooligomer/fluorescein
      composites and parent fluorescein gave the colorless solutions under similar
      conditions. On the other hand, unexpectedly, such brilliant yellow-colored
      solutions provided by these fluorinated nanocomposites completely disappeared in
      aprotic solvents such as N,N-dimethylformamide, dimethyl sulfoxide, and
      tetrahydrofuran. Thus, these fluorinated fluorescein nanocomposites can exhibit a
      coloring-decoloring behavior through solvatochromic response.

PMID- 22484166
TI  - Phase behaviour of casein micelles and barley beta-glucan polymer molecules in
      dietary fibre-enriched dairy systems.
AB  - Enrichment of colloidal dairy systems with dietary fibre frequently causes
      quality defects because of phase separation. We investigate phase separation in
      skimmed milk enriched with Glucagel (a commercial product made from barley that
      is predominantly comprised of the polysaccharide beta-glucan). The driving force
      for phase separation was depletion flocculation of casein micelles in the
      presence of molecules of the polysaccharide. Depending on the volume fraction of
      casein micelles and the concentration of Glucagel, the stable system phase
      separated either as a transient gel or as a sedimented system. The rate at which
      phase separation progressed also depended on the volume fraction of casein
      micelles and the concentration of Glucagel. To confirm the role of depletion
      flocculation in the phase separation process, enzymatic reduction in the
      molecular weight of beta-glucan was shown to limit the range of attraction
      between micelles and allow the stable phase to exist at a higher beta-glucan
      concentration for any given volume fraction of casein micelles. These phase
      diagrams will be useful to dairy product manufacturers striving to improve the
      nutrient profile of their products while avoiding product quality impairment.

PMID- 22484167
TI  - Effect of water hardness on surface tension and dilational visco-elasticity of
      sodium dodecyl sulphate solutions.
AB  - The complementary drop and bubble profile analysis and maximum bubble pressure
      tensiometry are used to measure the dynamic surface tension of aqueous SDS
      solutions in the presence of hardness salts (CaCl(2) and MgCl(2) in the ratio of
      2:1 at concentrations of 6 and 40FH). The presence of hardness salts results in
      an essential increase of the SDS adsorption activity, which indicates the
      formation of Ca(DS)(2) and Mg(DS)(2) in the SDS solutions. The surface tension
      isotherms of SDS in presence of Ca(DS)(2) and Mg(DS)(2) are described using the
      generalised Frumkin model. The presence of hardness salts accelerates the ageing
      of SDS solutions as compared with the addition of 0.01 M NaCl due to a faster
      hydrolysis and hence formation of dodecanol. These results are used to estimate
      the possible concentration of dodecanol in the studied SDS solutions. The buoyant
      bubble profile method with harmonic surface oscillations is used to measure the
      dilational rheology of SDS solutions in presence of hardness salts in the
      frequency range between 0.005 Hz and 0.2 Hz. The visco-elasticity modulus in the
      presence of hardness salts is higher as compared with its values in the presence
      of 0.01 M NaCl additions. The ageing of SDS solutions leads to an essential
      increase of the visco-elastic modulus.

PMID- 22484168
TI  - Wettability determined by capillary rise with pressure increase and hydrostatic
      effects.
AB  - Capillary rise is the basis of some methods that are widely applied for the
      determination of contact angles as well as wettabilities of small particles. The
      equivalent hydraulic radius r(d) in the Classical Washburn equation is assumed to
      be particle-specific. But it seems that r(d) is not always constant when the type
      of liquids is different. The new equation with the pressure increment and the
      hydrostatic effects are theoretically derived based on the Washburn equation, so
      contact angles of small particles can be measured experimentally independently of
      r(d). The result shows the validity of the proposed method, and therefore, it
      becomes possible to accurately measure the wettability of small particles.

PMID- 22484170
TI  - Oxygen adsorption induced superhydrophilic-to-superhydrophobic transition on
      hierarchical nanostructured CuO surface.
AB  - Hierarchical nanostructured CuO surface was embellished to amplify the
      wettability. The pristine superhydrophilic CuO surface spontaneously transited to
      be superhydrophobic after exposed in air at room temperature for about 3 weeks.
      The wettability change is attributed to the adsorption of oxygen molecules on the
      topmost layer according to the surface chemical analysis. The adsorbed oxygen
      molecules could be removed by dipping the sample into l-Ascorbic acid solution
      for 10 s, leading to the recovery of the pristine superhydrophilicity.

PMID- 22484169
TI  - Micromechanical cohesion force measurements to determine cyclopentane hydrate
      interfacial properties.
AB  - Hydrate aggregation and deposition are critical factors in determining where and
      when hydrates may plug a deepwater flowline. We present the first direct
      measurement of structure II (cyclopentane) hydrate cohesive forces in the water,
      liquid hydrocarbon and gas bulk phases. For fully annealed hydrate particles, gas
      phase cohesive forces were approximately twice that obtained in a liquid
      hydrocarbon phase, and approximately six times that obtained in the water phase.
      Direct measurements show that hydrate cohesion force in a water-continuous bulk
      may be only the product of solid-solid cohesion. When excess water was present on
      the hydrate surface, gas phase cohesive forces increased by a factor of three,
      suggesting the importance of the liquid or quasi-liquid layer (QLL) in
      determining cohesive force. Hydrate-steel adhesion force measurements show that,
      when the steel surface is coated with hydrophobic wax, forces decrease up to 96%.
      As the micromechanical force technique is uniquely capable of measuring hydrate
      surface forces with variable contact time, the present work contains significant
      implications for hydrate applications in flow assurance.

PMID- 22484171
TI  - Solute-solvent halogen bonding during adsorption on silver nanostructures.
AB  - We offer here evidence for halogen bonding induced by silver nanoparticles (SNPs)
      in a multilayer containing 4-iodobenzoate ion (4IBI) and CCl(4). SERS experiments
      show in the monolayer that CCl(4) does not adsorb and 4-iodobenzoic acid (4IBA)
      adsorbs as 4IBI. SEIRA experiments reveal that 4IBI forms in the multilayer
      during deposition from CCl(4) on SNPs. Further infrared experiments on clean
      BaF(2) prove that 4IBI formation caused by underlying SNPs was necessary for
      CCl(4) inclusion in a 4IBI multilayer. Several potential scenarios involving
      intermolecular attraction between CCl(4) and 4IBI are proposed to explain the
      results. Although halogen bonding involving solvents has been theoretically and
      experimentally demonstrated in solution phase chemistry, in bulk crystals, and at
      the monolayer level, here it is shown that halogen bonding interactions can also
      be significant in multilayer films. Results from this work will likely impact a
      range of applications across diverse fields where halogen bonding in thin films
      and nucleation chemistry are important.

PMID- 22484172
TI  - Effect of adsorbed poly(ethylene glycol) on the gelation evolution of Laponite
      suspensions: aging time-polymer concentration superposition.
AB  - The effects of the concentration of polyethylene glycol (PEG) and NaCl on the
      gelation kinetics of aqueous Laponite suspensions were investigated. The PEG
      concentration c(p) was increased from 0.063 wt.% to 1.0 wt.%, and the NaCl
      concentration c(s) was increased from 3.0 mM to 5.0 mM. The gelation process was
      monitored with the small amplitude oscillatory shear (SAOS) rheology. At each
      NaCl concentration, the time curves of storage and loss moduli G' and G" at
      different PEG concentrations were shifted horizontally to construct a master
      curve. Master curves for different NaCl concentrations were shifted further into
      a main master curve. The results were understood in terms of an increase in
      steric repulsion with increasing c(p). A model based on the theory of interaction
      limited coagulation was proposed to describe the dependence of the shift factor
      on the PEG concentration, taking into account of the interactions between
      particles. The quantitative description of the observed results has been achieved
      with this model.

PMID- 22484173
TI  - Fluorometric determination of inulin using 5-quinolineboronic acid and inulinase.
AB  - Inulin is a polysaccharide composed mainly of D-fructose units and is the most
      reliable indicator of the glomerular filtration rate. We have proposed an inulin
      detection method that involves the hydrolysis of inulin to D-fructose using
      inulinase and the selective binding of D-fructose from inulin using 5
      quinolineboronic acid. In this method, the fluorescence of 5-quinolineboronic
      acid increases, depending on inulin concentration. For inulin in plasma, the
      detection and quantitation limits were calculated to be 3.7 and 11 MUg/ml,
      respectively.

PMID- 22484174
TI  - Differential viral propagation and induction of apoptosis by grouper iridovirus
      (GIV) in cell lines from three non-host species.
AB  - Grouper iridovirus (GIV), belonging to the Ranavirus genus of the Iridoviridae
      family, was demonstrated to differentially express viral genes and induce
      apoptosis in three non-host fish cell lines rainbow trout monocyte/macrophage
      (RTS11), chinook salmon embryonic (CHSE-214) and fathead minnow Epithelioma
      papulosum cyprinid (EPC). These cells were challenged with GIV and virus entry
      into all three cell lines was confirmed by the expression of viral immediate
      early genes. The expression of the late major capsid protein gene was detected in
      CHSE-214 and EPC, but not in RTS11, suggesting an earlier termination in the
      viral replication cycle in RTS11. Approximately 12h after infection with GIV,
      cell death was prominent in all three non-host cell lines. Death was later
      confirmed to be apoptosis by the presence of chromosomal DNA fragmentation and
      phosphatidylserine externalization. To determine whether apoptosis was protein
      related or gene expression related, the three cell lines were challenged with
      heat-inactivated GIV and UV-treated GIV (GIV(UV)). The heat inactivation
      abolished apoptosis in all three cell lines, but each cell line responded
      differently to GIV(UV). Relative to GIV, GIV(UV) caused no apoptosis in CHSE-214,
      decreased apoptosis in RTS11, and increased apoptosis in EPC. These results
      suggest that early GIV gene expression was needed for apoptosis in CHSE-214 but
      impeded apoptosis in EPC. At the cellular level, only EPC is a permissive host as
      EPC was the only cell line of the three capable of producing a moderate increase
      in virus titer. The three non-host cell lines present a good system for
      potentially identifying different components of GIV-induced apoptotic pathways in
      future studies.

PMID- 22484175
TI  - The dual organization of P-bodies revealed by immunoelectron microscopy and
      electron tomography.
AB  - Processing bodies (P-bodies) are cytoplasmic non-membranous domains involved in
      the regulation of eukaryotic gene expression. Since their discovery, several
      studies using fluorescence-based strategies have uncovered their pivotal role in
      mRNA metabolism, particularly during translation repression and/or mRNA
      degradation. Yet, P-bodies still remain a "black box" in which numerous proteins
      accumulate next to RNAs to regulate their fate by unknown mechanisms. In this
      study, we investigated the ultrastructural organization of P-bodies in human
      cells. Using a wide range of original electron microscopy strategies, including
      high-pressure freezing and freeze substitution, we found that P-bodies are huge
      ribonucleoprotein complexes located in the close proximity of mitochondria and
      ribosomes, in which regulatory factors exhibit differential localization
      depending on their activity on mRNAs. We describe the first experiment pairing
      immunogold labeling with electron tomography (immunoelectron tomography) of a
      human P-body. Overall, the results depict a P-body organization that comprises at
      least two distinct compartments: a dense core on which peripheral protrusions are
      anchored.

PMID- 22484177
TI  - A three-dimensional FRET analysis to construct an atomic model of the actin
      tropomyosin-troponin core domain complex on a muscle thin filament.
AB  - It is essential to know the detailed structure of the thin filament to understand
      the regulation mechanism of striated muscle contraction. Fluorescence resonance
      energy transfer (FRET) was used to construct an atomic model of the actin
      tropomyosin (Tm)-troponin (Tn) core domain complex. We generated single-cysteine
      mutants in the 167-195 region of Tm and in TnC, TnI, and the beta-TnT 25-kDa
      fragment, and each was attached with an energy donor probe. An energy acceptor
      probe was located at actin Gln41, actin Cys374, or the actin nucleotide-binding
      site. From these donor-acceptor pairs, FRET efficiencies were determined with and
      without Ca(2+). Using the atomic coordinates for F-actin, Tm, and the Tn core
      domain, we searched all possible arrangements for Tm or the Tn core domain on F
      actin to calculate the FRET efficiency for each donor-acceptor pair in each
      arrangement. By minimizing the squared sum of deviations for the calculated FRET
      efficiencies from the observed FRET efficiencies, we determined the location of
      Tm segment 167-195 and the Tn core domain on F-actin with and without Ca(2+). The
      bulk of the Tn core domain is located near actin subdomains 3 and 4. The central
      helix of TnC is nearly perpendicular to the F-actin axis, directing the N
      terminal domain of TnC toward the actin outer domain. The C-terminal region in
      the I-T arm forms a four-helix-bundle structure with the Tm 175-185 region. After
      Ca(2+) release, the Tn core domain moves toward the actin outer domain and closer
      to the center of the F-actin axis.

PMID- 22484176
TI  - Characterization of Vibrio cholerae Hfq provides novel insights into the role of
      the Hfq C-terminal region.
AB  - Hfq is a bacterial RNA binding protein that facilitates small RNA-mediated
      posttranscriptional gene regulation. In Vibrio cholerae, Hfq and four Hfq
      dependent small RNAs are essential for the expression of virulence genes, but
      little is known about this mechanism at the molecular level. To better understand
      V. cholerae Hfq structure and mechanism, we characterized the protein, alongside
      Escherichia coli Hfq for comparison, using biochemical and biophysical
      techniques. The N-terminal domain (NTD) of the two proteins is highly conserved,
      but the C-terminal regions (CTRs) vary in both sequence and length. Small-angle X
      ray scattering studies showed that both proteins adopt a star-shaped hexameric
      structure in which the conserved NTD adopts the expected Sm fold while the
      variable CTR is disordered and extends radially outwards from the folded core.
      Despite their structural similarity, SDS-PAGE stability assays and collision
      induced dissociation mass spectrometry revealed that the V. cholerae hexamer is
      less stable than that of E. coli. We propose that this is due to minor
      differences between the intersubunit interface formed by the NTDs and the ability
      of the E. coli CTR to stabilize this interface. However, based on electrophoretic
      mobility shift assays, the divergent CTRs do appear to perform a common function
      with regard to RNA-binding specificity. Overall, the similarities and differences
      in the fundamental properties of V. cholerae and E. coli Hfq provide insight into
      their assembly and molecular mechanisms.

PMID- 22484178
TI  - Partitioning and diffusion of parathion in human dermis.
AB  - A previously developed method employing the use of a dialysis membrane in series
      with human dermis tissue mounted in side-by-side diffusion cells was utilized to
      observe the effects of the presence of soluble proteins in the donor compartment
      on the measured transport parameters of parathion. In the presence of the
      dialysis membrane the partition coefficient was significantly lower and the
      diffusion coefficient significantly higher than those determined in its absence;
      however, the difference was less than that previously determined for the more
      highly protein bound compound, diclofenac. The result suggests the dialysis
      membrane method is important for studying permeants that are more than about 87%
      bound to soluble proteins in the dermis. The results are discussed in the context
      of a predictive model for partitioning and transport of low molecular weight
      solutes in human dermis.

PMID- 22484180
TI  - Ginsenoside Rh2 inhibits osteoclastogenesis through down-regulation of NF-kappaB,
      NFATc1 and c-Fos.
AB  - Ginsenoside Rh2 is one of the most active components of red ginseng, controlling
      cancer and other metabolic diseases including osteoclast differentiation.
      However, the molecular mechanism underlying the inhibition of osteoclast
      differentiation by ginsenoside Rh2 remains poorly understood. In the present
      study, it was found that ginsenoside Rh2 suppressed osteoclast differentiation
      from bone marrow macrophages (BMMs) treated with receptor activator of nuclear
      factor kappaB ligand (RANKL) without any cytotoxicity. Ginsenoside Rh2
      significantly reduced RANKL-induced expression of transcription factors, c-Fos
      and nuclear factor of activated T-cells (NFATc1), as well as osteoclast markers,
      TRAP and OSCAR. In defining the signaling pathways, ginsenoside Rh2 was shown to
      moderately inhibit NF-kappaB activation and ERK phosphorylation in response to
      RANKL stimulation in BMM cells without any effect on p38 and c-Jun N-terminal
      kinase (JNK). Finally, ginsenoside Rh2 blocked osteoporosis in vivo as confirmed
      by restored bone mineral density (BMD) and other markers associated osteoclast
      differentiation. Hence, it is suggested that ginsenoside Rh2 could suppress RANKL
      induced osteoclast differentiation in vitro and in vivo through the regulation of
      c-Fos and NFATc1 expressions, not excluding the involvement of NF-kappaB and ERK.
      Ginsenoside Rh2 is also suggested to be developed as a therapeutic drug for
      prevention and treatment of osteoporosis.

PMID- 22484181
TI  - Expression of osteoblastic and osteoclastic genes during spontaneous regeneration
      and autotransplantation of goldfish scale: a new tool to study intramembranous
      bone regeneration.
AB  - Complementary DNA of osteoblast-specific genes (dlx5, runx2a, runx2b, osterix,
      RANKL, type I collagen, ALP, and osteocalcin) was cloned from goldfish (Carassius
      auratus) scale. Messenger RNA expressions were analyzed during spontaneous scale
      regeneration. Dlx5 had an early peak of expression on day 7, whereas osterix was
      constantly expressed during days 7-21. Runx2, a major osteoblastic transcription
      factor in mammalian bone, did not show any significant expression. The
      expressions of two functional genes, type I collagen and ALP, continually
      increased after day 7, while that of osteocalcin increased on day 14. As for
      osteoclastic markers, in addition to the cloning of two functional genes, TRAP
      and cathepsin K, in our previous study, we here cloned the transcription factor
      NFATc1 to use as an early osteoclastic marker. Using these bone markers, we
      investigate the signal key that controls the onset of scale resorption and
      regeneration by performing intra-scale-pocket autotransplantation of five groups
      of modified scales, namely, 1) methanol-fixed scale, 2) proteinase K-treated cell
      free scale, 3) polarity reversal (upside-down) scale, 4) U-shape trimmed scale,
      and 5) circular-hole perforated scale. In this autotransplantation, each
      ontogenic scale was pulled out, modified, and then re-inserted into the same
      scale pocket. At post-transplant, inside the pockets of all modified transplant
      groups, new regenerating scales formed, attaching to the ongoing resorbed
      transplants. Autotransplantation of methanol-fixed scale, proteinase K-treated
      cell-free scale, and polarity reversal (upside-down) scale triggered scale
      resorption and scale regeneration. These two processes of scale resorption and
      regeneration occurred in accordance with osteoclastic and osteoblastic marker
      gene expressions. These results were microscopically confirmed using TRAP and ALP
      staining. Regarding the autotransplantation of U-shape trimmed and circular-hole
      perforated scales, new scales regenerated and grew at the trimmed/perforated part
      of each transplant, while scale resorption occurred apparently only around the
      trimmed/perforated area. In contrast, no scale resorption or regeneration was
      detected in sham transplantations. Our finding suggests that loss of correct cell
      to-cell contact between the scale-pocket lining cells and the scale cortex cells
      is the key to switch on the onset of scale resorption and regeneration. Overall,
      the present study shows that goldfish scale regeneration shares similarities in
      gene expression with intramembranous bone regeneration. Improved understanding of
      goldfish scale regeneration will help elucidate the process of intramembranous
      bone regeneration and make goldfish scale a possible new tool to study bone
      regeneration.

PMID- 22484179
TI  - Brain stimulation in the treatment of chronic neuropathic and non-cancerous pain.
AB  - Chronic neuropathic pain is one of the most prevalent and debilitating disorders.
      Conventional medical management, however, remains frustrating for both patients
      and clinicians owing to poor specificity of pharmacotherapy, delayed onset of
      analgesia and extensive side effects. Neuromodulation presents as a promising
      alternative, or at least an adjunct, as it is more specific in inducing analgesia
      without associated risks of pharmacotherapy. Here, we discuss common clinical and
      investigational methods of neuromodulation. Compared to clinical spinal cord
      stimulation (SCS), investigational techniques of cerebral neuromodulation, both
      invasive (deep brain stimulation [DBS] and motor cortical stimulation [MCS]) and
      noninvasive (repetitive transcranial magnetic stimulation [rTMS] and transcranial
      direct current stimulation [tDCS]), may be more advantageous. By adaptively
      targeting the multidimensional experience of pain, subtended by integrative pain
      circuitry in the brain, including somatosensory and thalamocortical, limbic and
      cognitive, cerebral methods may modulate the sensory-discriminative, affective
      emotional and evaluative-cognitive spheres of the pain neuromatrix. Despite
      promise, the current state of results alludes to the possibility that cerebral
      neuromodulation has thus far not been effective in producing analgesia as
      intended in patients with chronic pain disorders. These techniques, thus, remain
      investigational and off-label. We discuss issues implicated in inadequate
      efficacy, variability of responsiveness, and poor retention of benefit, while
      recommending design and conceptual refinements for future trials of cerebral
      neuromodulation in management of chronic neuropathic pain. PERSPECTIVE: This
      critical review focuses on factors contributing to poor therapeutic utility of
      invasive and noninvasive brain stimulation in the treatment of chronic
      neuropathic and pain of noncancerous origin. Through key clinical trial design
      and conceptual refinements, retention and consistency of response may be
      improved, potentially facilitating the widespread clinical applicability of such
      approaches.

PMID- 22484182
TI  - Thirty-nine-year-old with familial colon cancer, and variant of undetermined
      significance in MSH6.

PMID- 22484183
TI  - Introduction: Advanced cutaneous malignancies.

PMID- 22484184
TI  - Advances in the chemoprevention of non-melanoma skin cancer in high-risk organ
      transplant recipients.
AB  - Patients with a history of more than four basal cell carcinomas (BCCs) or
      squamous cell carcinomas (SCCs) are at high risk for developing further skin
      cancers. Immunosuppressed patients, especially solid organ transplantation
      patients, harbor a higher risk of developing SCC. Systemic retinoids have been
      demonstrated to possess chemoprophylactic properties in the treatment of non
      melanoma skin cancer. This article reviews the efficacies of the available oral
      retinoid agents in the chemoprophylaxis of SCCs in high-risk solid organ
      transplant recipients.

PMID- 22484185
TI  - Advances in the treatment of Basal cell carcinoma: Hedgehog inhibitors.
AB  - Basal cell carcinoma (BCC) is the most common tumor of the skin and can result in
      significant morbidity as well as costs. The discovery of aberrant Hedgehog (HH)
      signaling in patients with genetic propensity to develop BCCs has resulted in a
      better understanding of the genetic abnormalities leading to the development of
      BCC. The current state of knowledge with regard to the genetics of BCC is
      discussed. Existing therapies are reviewed, in particular new targeted therapies
      to the HH signaling pathway that have resulted in a landmark breakthrough for
      patients with refractory BCC. Data from recent and ongoing trials are presented.

PMID- 22484186
TI  - Chemotherapy of squamous cell carcinoma of the skin.
AB  - The role of systemic chemotherapy with cytotoxic agents in squamous cell
      carcinoma of the skin remains uncertain. A number of agents in combination have
      been reported to induce high rates of remission, either alone or as a component
      of a multidisciplinary management plan. Fragmentary data suggest that the most
      benefit is achieved when chemotherapy is applied to patients with advanced local
      disease not easily treated with surgery either due to location (eg, on the face)
      or comorbidity. Concurrent chemoradiation has been recommended for the control of
      extensive lymph node involvement as a result of experience derived from similar
      studies in patients with squamous cell carcinomas of the head and neck, cervix,
      and anus. No standard treatment of metastatic disease has been formulated,
      although combinations of cisplatin with 5-fluorouracil (5-FU), doxorubicin, or
      bleomycin have demonstrated some degree of efficacy, achieving complete responses
      (CRs) in some cases. Clearly, the relative rarity of patients with high-risk,
      potentially fatal, squamous cell carcinoma of the skin has limited prospective
      efforts to define ideal management. As our awareness of the increasing numbers of
      such problem patients becomes clear, hopefully more efforts will be forthcoming.

PMID- 22484187
TI  - Recent advances in the management of cutaneous lymphomas.
AB  - The treatment options for patients with primary cutaneous B- and T-cell lymphomas
      are as diverse as the diseases themselves, including both skin-directed and
      systemic therapies. Long-term remission can be attained in many cases; however,
      no treatment is curative with the possible exception of allogeneic stem cell
      transplant. Improved insight into the molecular biology and pathophysiology of
      these diseases has led to the development of novel drugs and targeted therapies,
      including monoclonal antibodies and antimetabolites, as well as improved
      radiotherapeutic techniques. We aim to summarize these new and emerging treatment
      modalities, and to outline how they may be integrated into the clinical
      management of patients with primary cutaneous lymphoma (CL).

PMID- 22484188
TI  - Recent advances in the understanding of the genetics, etiology, and treatment of
      Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive skin malignancy. The growing
      incidence and recognition of this cancer in elderly or immunosuppressed
      individuals suggests that it is becoming an increasing clinical challenge. MCC
      recently has been demonstrated to have a probable viral pathogenesis related to a
      novel member of the polyomavirus (termed Merkel cell polyomavirus [MCV]). The
      molecular pathogenesis of viral carcinogenesis is currently being worked out in
      MCC. Current diagnostic and therapeutic strategies are discussed, with an eye
      toward the future development of molecularly targeted treatments.

PMID- 22484190
TI  - Recent advances in pathologic evaluation and reporting of melanoma.
AB  - Recent changes to the staging of melanoma, coupled with advances in surgical and
      medical treatment, have resulted in new methods for diagnostic evaluation and
      reporting of melanocytic lesions by pathologists. This review provides an update
      on recent changes in evaluation and reporting of primary melanoma, evaluation of
      regional lymph nodes, especially sentinel nodes, and the workup of distant
      metastatic melanoma specimens. A brief summary of commercially available
      molecular diagnostic techniques and their application to practice is included.

PMID- 22484189
TI  - Advances in the systemic treatment of cutaneous sarcomas.
AB  - Cutaneous sarcomas are a rare subset of soft tissue sarcomas. These tumors are
      primarily managed with definitive surgical resection; however, upon unresectable
      recurrence or metastatic spread, systemic therapy is warranted. As with other
      sarcomas, these treatments have classically included cytotoxic chemotherapy
      programs that were associated with variable response rates and poor overall
      survival. Recently, major advances have been made in the understanding of the
      molecular biology of these tumors, and treatment paradigms are changing. Multiple
      pathways have been documented to be important in the growth of cutaneous
      sarcomas, including receptor tyrosine kinases such as platelet-derived growth
      factor receptor, insulin-like growth factor receptor and KIT. Dysregulated
      angiogenesis, through vascular endothelial growth factor (VEGF) and other
      pathways, is also associated with the growth of these tumors. In this review, we
      discuss the current standard therapies of cutaneous sarcoma and the recent
      advances and ongoing investigations into cutaneous sarcoma biology.

PMID- 22484191
TI  - Advances in the treatment of metastatic melanoma: new immunomodulatory agents.
AB  - Antibodies targeting ligand-receptor interactions that control activation and
      function of immune cell subsets such as dendritic cells (DCs) and in particular T
      cells have shown substantial promise for the treatment of unresectable or
      metastatic melanoma. The furthest in development, the antagonist anti-CTLA-4
      antibodies, which block a key negative regulator of T-cell activation, have been
      shown to produce durable clinical responses in a small subset of patients. One of
      these antibodies, ipilimumab, also prolonged overall survival in two randomized
      phase III studies, leading to regulatory approval for marketing by the US Food
      and Drug Administration (FDA). Consistent with its mechanism of action, the major
      adverse events from anti-CTLA4 stem from immune-mediated inflammatory reactions.
      Paradigms for the administration of anti-CTLA-4 and newer immunomodulatory agents
      have evolved to effectively manage the adverse events and also to consider unique
      patterns and kinetics of tumor response. Early clinical studies of another
      antagonist antibody, which blocks the co-inhibitory receptor PD-1 on activated T
      cells, also are showing promising activity in metastatic melanoma. The clinical
      efficacy of cancer vaccines, which in broad terms also includes intratumorally
      administered agents designed to increase tumor immunogenicity, is being
      investigated in ongoing phase III trials, and various new agents are in earlier
      development, including newer cytokines and T-cell or DC co-stimulatory
      antibodies, some of which have already demonstrated clinical activity in advanced
      disease. Current data suggest that focusing development on agents countering
      immune suppression in the tumor microenvironment or blocking regulatory
      checkpoints to T-cell activation may have the greatest clinical yield.
      Combinations of immunomodulatory agents also may improve clinical activity,
      although possibly at a cost of greater toxicity. A major challenge for the field
      will be to develop predictive biomarkers of response, and to identify mechanisms
      of resistance to existing agents that can be addressed in subsequent clinical
      trials.

PMID- 22484192
TI  - The current state of targeted therapy in melanoma: this time it's personal.
AB  - Treatment of metastatic melanoma has long been a challenge. Over the past 8 years
      significant advances have been made in understanding the genetic changes that
      drive melanoma development and progression. These studies have shown melanoma to
      be a heterogeneous group of tumors, driven by a diverse array of oncogenic
      mutations. There is now good evidence that activating mutations in the
      serine/threonine kinase BRAF and the receptor tyrosine kinase KIT constitute good
      therapeutic targets for restricted subgroups of melanoma. In this article, we
      discuss the genetics and etiology of cutaneous and noncutaneous melanoma and
      review some of the latest preclinical and clinical data on the new targeted
      therapy agents that are beginning to make an impact on the lives of melanoma
      patients.

PMID- 22484193
TI  - Advances in the treatment of metastatic melanoma: adoptive T-cell therapy.
AB  - Metastatic melanoma is notoriously resistant to chemotherapy and radiotherapy
      regimens. The prospect for newly diagnosed metastatic melanoma patients is grim,
      with a median survival of less than 1 year. Currently, the only therapies
      resulting in long-term disease-free intervals, high-dose interleukin-2 (IL-2) and
      more recently anti-CTLA-4, work through activation of the immune system. However,
      with both therapies the response rate is low. Advances in our knowledge of how
      the immune system interacts with cancer have led to a number of strategies to
      manipulate anti-tumor immune responses through immunotherapy. This review will
      focus on one avenue of immunotherapy using the transfer of T cells referred to as
      "adoptive cell therapy" (ACT), which involves the ex vivo expansion of autologous
      tumor-specific T cells to large numbers that are ultimately transferred back to
      the patient to boost anti-tumor immunity. This approach has been shown to be
      effective in the treatment of virally induced cancers, as well as metastatic
      melanoma. Recent successes with ACT hold promise and further emphasize the
      tremendous potential benefit of harnessing the immune system in the fight against
      cancer.

PMID- 22484194
TI  - Advances in the management of cutaneous toxicities of targeted therapies.
AB  - Contrary to what might have been expected, the effects of targeted therapies are
      not limited to the cancer cells and are unfortunately associated with many and
      numerous adverse events. Dermatologic manifestations are among the most
      frequently observed, and, when severe and/or protracted, they inevitably impact
      the quality of life of patients. Management of these various side effects is
      empirical and mostly based on expert advice and consensus. We will review the
      skin side effects of EGFR, VEGFR, KIT, platelet-derived growth factor receptor
      (PDGFR), and BCR-ABL inhibitors, as well as mTOR inhibitors.

PMID- 22484195
TI  - Doxil(r)--the first FDA-approved nano-drug: lessons learned.
AB  - Doxil(r), the first FDA-approved nano-drug (1995), is based on three unrelated
      principles: (i) prolonged drug circulation time and avoidance of the RES due to
      the use of PEGylated nano-liposomes; (ii) high and stable remote loading of
      doxorubicin driven by a transmembrane ammonium sulfate gradient, which also
      allows for drug release at the tumor; and (iii) having the liposome lipid bilayer
      in a "liquid ordered" phase composed of the high-T(m) (53  degrees C)
      phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively
      targeted" to tumors and its doxorubicin is released and becomes available to
      tumor cells by as yet unknown means. This review summarizes historical and
      scientific perspectives of Doxil development and lessons learned from its
      development and 20 years of its use. It demonstrates the obligatory need for
      applying an understanding of the cross talk between physicochemical, nano
      technological, and biological principles. However, in spite of the large reward,
      ~2 years after Doxil-related patents expired, there is still no FDA-approved
      generic "Doxil" available.

PMID- 22484196
TI  - "Targeting" nanoparticles: the constraints of physical laws and physical
      barriers.
AB  - In comparison to the complexities of the body, its organs, its normal and
      aberrant cells, many nanoparticles will appear to be relatively simple objects.
      This view is deceptive because the physicochemical properties of nanosystems,
      although quite well understood on the basis of material science, surface science
      and colloid theory, are far from simple in practice. While their properties are
      largely controllable in vitro, often purportedly "designed", their administration
      by any route changing environments conspires to produce additional layers of
      complexity. Some of the key physical laws and physicochemical parameters
      governing the fate of nanoparticles on their journey from point of intravenous
      administration to desired destinations such as tumors are discussed. Much of the
      science relevant to nanocarrier based targeting has been elaborated in studying
      purely physical phenomena, but there can be found therein many analogies with
      biological systems. These include factors that impede quantitative targeting:
      diffusion in complex media, aggregation and flocculation, hindered behavior of
      particles in confined spaces, jamming and dispersion in flow. All of these have
      the ability to influence fate and destination. Most of the critical processes are
      particle size dependent but not always linearly so. Virtually all processes in
      vivo involve an element of probability. Particle size and properties can be
      controlled to a large extent, but stochastic processes cannot by definition.
      Progress has been made, but the quantitative delivery of a nanocarrier to defined
      sites in tumors is neither inevitable nor yet predictable.

PMID- 22484197
TI  - Effective transgene expression without toxicity by intraperitoneal administration
      of PEG-detachable polyplex micelles in mice with peritoneal dissemination.
AB  - Block copolymer of poly(ethylene glycol)-block-poly{N-[N-(2-aminoethyl)-2
      aminoethyl]aspartamide} (PEG-P[Asp(DET)]) has been originally introduced as a
      promising gene carrier by forming a nanomicelle with plasmid DNA. In this study,
      the polyplex micelle of PEG-SS-P[Asp(DET)], which disulfide linkage (SS) between
      PEG and cationic polymer can detach the surrounding PEG chains upon intracellular
      reduction, was firstly evaluated with respect to in vivo transduction efficiency
      and toxicity in comparison to that of PEG-P[Asp(DET)] in peritoneally
      disseminated cancer model. Intraperitoneal (i.p.) administration of PEG-SS
      P[Asp(DET)] polyplex micelles showed a higher (P<0.05) transgene expression
      compared with PEG-P[Asp(DET)] in tumors. In contrast, the delivered distribution
      of the micelles was not different between the two polyplex micelles. PEG-SS
      P[Asp(DET)] micelle encapsulating human tumor necrosis factor alpha (hTNF-alpha)
      gene exhibits a higher antitumor efficacy against disseminated cancer compared
      with PEG-P[Asp(DET)] or saline control. No hepatic and renal toxicities were
      observed by the administration of polyplex micelles. In conclusion, PEG
      detachable polyplex micelles may represent an advantage in gene transduction in
      vivo over PEG-undetachable polyplex micelles after i.p. administration for
      peritoneal dissemination of cancer.

PMID- 22484198
TI  - Purification and characterization of human IL-10/Fc fusion protein expressed in
      Pichia pastoris.
AB  - Interleukin (IL)-10 is an anti-inflammatory cytokine that could be potentially
      applied for clinical therapy. However, its short circulating half-life in the
      serum limits its clinical applications. In this study, we designed a fusion
      protein containing human IL-10 and an IgG Fc fragment (hIL-10/Fc), and expressed
      it in Pichia pastoris. This hIL-10/Fc fusion protein was purified from the
      culture supernatant using MabSelect affinity chromatography and size-exclusion
      chromatography. The hIL-10/Fc yield was about 5mg/L in shake flasks, with purity
      exceeding 95%. In addition, the hIL-10/Fc fusion protein suppressed the
      phytohemagglutinin-induced IFN-gamma production in human peripheral blood
      mononuclear cells. Pharmacokinetic study also revealed that hIL-10/Fc has a
      prolonged circulating half-life of about 30h in rats. More importantly, the hIL
      10/Fc fusion protein displayed highly specific biological activity, which was
      slightly higher than that of the commercial recombinant human IL-10 (rhIL-10).
      Therefore, P. pastoris is useful in the large-scale production of hIL-10/Fc
      fusion protein for both research and therapeutic applications.

PMID- 22484199
TI  - In vivo and in vitro characterization of TEV protease mutants.
AB  - Tobacco etch virus protease (TEVp) is frequently applied in the cleavage of
      fusion protein. However, production of TEV protease in Escherichia coli is
      hampered by low yield and poor solubility, and auto-cleavage of wild type TEVp
      gives rise to the loss-of-function. Previously it was reported that TEVp S219V
      displayed more stability, and TEVp variant containing T17S/N68D/I77V and double
      mutant L56V/S135G resulted in the enhanced production and solubility,
      respectively. Here, we introduced T17S/N68D/I77V in TEVp S219V to generate TEVpM1
      and combined five amino acid mutations (T17S/L56V/N68D/I77V/S135G) in TEVp S219V
      to create TEVpM2. Among TEVp S219V, and two constructed variants, TEVpM2
      displayed highest solubility and catalytic activity in vivo, using EmGFP as the
      solubility reporter, and the designed fusion protein as in vivo substrate
      containing an N-terminal hexahistidine tagged GST, a peptide sequence for
      thrombin and TEV cut and E. coli diaminopropionate ammonia-lyase. The purified
      TEVp mutants fused with double hexahistidine-tag at N and C terminus showed
      highest yield, solubility and cleavage efficiency. Mutations of five amino acid
      residues in TEVpM2 slightly altered protein secondary structure conformed by
      circular dichroism assay.

PMID- 22484200
TI  - Two-dimensional pattern motion analysis uses local features.
AB  - Extensive research suggests that the visual system computes the direction of
      motion of a two-dimensional pattern from the motion of its oriented spatial
      frequency components. However, there is some evidence to suggest that the local
      features in a pattern are also important. In order to demonstrate that the local
      features contribute to motion perception we have created complex stimuli in which
      the oriented spatial frequency components have the same direction of motion but
      the local features move in different directions. The stimuli are multi-component
      plaid patterns with alternating high and low contrast rows. An analysis based on
      the oriented spatial frequency components predicts a uniform motion percept for
      the whole pattern. However, an analysis based on the local features in the
      pattern predicts that the high-contrast and low-contrast rows would be perceived
      to move in opposite directions. In a direction discrimination task, observers
      reported opposite directions of motion for small patches of the pattern that were
      centred on high and low contrast rows. This supports the hypothesis that the
      visual system uses local features when computing pattern motion. We show that a
      simple energy model with localised motion sensors that are broadly tuned for
      orientation could explain our results.

PMID- 22484201
TI  - Does BDNF genotype influence creative output in bipolar I manic patients?
AB  - INTRODUCTION: Creativity is a complex human ability influenced by affective and
      cognitive components but little is known about its underlying neurobiology.
      Bipolar Disorder (BD) is highly prevalent among creative individuals. Brain
      derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic
      factor, and has been implicated in the pathophysiology of BD. In contrast to the
      better functioning of the BDNF polymorphism (Val(66)Met) Val allele, the Met
      allele decreases BDNF transport and has been associated with worsened performance
      on several cognitive domains in euthymic BD subjects and controls. We
      hypothesized that the Val allele is associated with increased creativity in
      bipolar disorder. MATERIALS AND METHODS: Sixty-six subjects with BD (41 in manic
      and 25 in depressive episodes) and 78 healthy volunteers were genotyped for BDNF
      Val(66)Met and tested for creativity using the Barrow Welsh Art Scale (BWAS) and
      neuropsychological tests. RESULTS: Manic patients with the Val allele (Met-) had
      higher BWAS scores than Met+ carriers. This relationship was not observed among
      patients in depressive episodes or among control subjects. BDNF Met allele status
      showed no association with cognitive function in any of the groups. CONCLUSION:
      As postulated, these findings suggest that the better functioning allele of BDNF
      may selectively facilitate creative thinking in subjects with manic episodes, but
      not in controls or depressives. Further studies exploring the role of BDNF in the
      neurobiology of creativity in BD and in euthymic phases are warranted.

PMID- 22484202
TI  - Low plasma adiponectin levels in panic disorder.
AB  - BACKGROUND: The present study was performed to evaluate plasma adiponectin levels
      in the patients with PD. METHOD: The study group included a total of 28 patients
      (17 females, 11 males) and 23 age- and sex-matched healthy comparison subjects
      (10 females and 13 males). The plasma fasting glucose, total cholesterol,
      triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), and
      hemoglobin were measured. RESULTS: There were no differences in regard to plasma
      fasting glucose, total cholesterol, triglyceride, LDL, HDL, and hemoglobin levels
      between groups. However, the mean adiponectin levels were significantly lower in
      the patient group (26.96 +/- 9.92 ng/ml) compared to controls (37.63 +/- 23.17
      ng/ml) (t=-2.21; p=0.032). As for the ANCOVA analyses, it revealed the main
      effect of diagnosis on adiponectin levels (F=5.78, p=0.020) after BMI (body mass
      index) and gender as covariates. CONCLUSIONS: Consequently, the findings of our
      study suggest that there may be an interaction between panic disorder and plasma
      adiponectin. Moreover, they led us to consider that these patients should be also
      followed as cardiac problems.

PMID- 22484203
TI  - Brain white matter organisation in adolescence is related to childhood cerebral
      responses to facial expressions and harm avoidance.
AB  - While white matter structural integrity is likely to influence the responses to
      social-emotional stimuli and emotional regulation during development, no
      longitudinal data are available on such relationships. We investigated the
      relationships between white matter Fractional Anisotropy (FA) derived by DTI
      voxelwise Tract Based Spatial Statistics (TBSS) and tractography measured at ages
      14-15, and cerebral event-related N400 amplitudes in response to happy, neutral
      and angry facial expressions and Cloninger's Harm Avoidance (HA) measured at ages
      7-9. Whole-skeleton TBSS analyses revealed reduced FA associated to smaller N400
      amplitudes in response to anger, and to higher HA. Region-of-Interest TBSS
      analyses showed high correlations (ranging -0.69-0.82, p<0.01-0.001) between FA
      and N400 amplitudes across the Inferior Longitudinal, the Inferior
      Frontoccipital, and the left Uncinate Fasciculus, and between FA and Harm
      Avoidance in right Uncinate Fasciculus (-0.71, p<0.01). Tractography showed that
      these relationships were mainly present in the left Inferior Longitudinal and the
      right Inferior Fronto-Occipital Fasciculus for N400 amplitudes, and in the right
      Uncinate Fasciculus for HA. Ventral limbic pathways' white matter organisation
      affects the neural responses to expressions - such as anger - that are
      perceptually more challenging and/or communicate social rejection, and compounds
      the neural pathways that predispose to avoidant behaviour and shyness with
      strangers.

PMID- 22484204
TI  - A novel temporal filtering strategy for functional MRI using UNFOLD.
AB  - A major challenge for fMRI at high spatial resolution is the limited temporal
      resolution. The UNFOLD method increases image acquisition speed and potentially
      enables high acceleration factors in fMRI. Spatial aliasing artifacts due to
      interleaved k-space sampling are to be removed from the image time series by
      temporal filtering before statistical mapping in the time domain can be carried
      out. So far, low-pass filtering and multi-band filtering have been proposed.
      Particularly at high UNFOLD factors both methods are non-optimal. Low-pass
      filtering severely degrades temporal resolution and multi-band filtering leads to
      temporal autocorrelations affecting statistical modelling of activation. In this
      work, we present a novel temporal filtering strategy that significantly reduces
      temporal autocorrelations compared to multi-band filtering. Two datasets (finger
      tapping and resting state) were post-processed using the proposed and the multi
      band filter with varying set-ups (i.e. transition bands). When the proposed
      filtering strategy was used, a linear regression analysis revealed that the
      number of false positives was significantly decreased up to 34% whereas the
      number of activated voxels was not significantly affected for most filter
      parameters. In total, this led to an effective increase in the number of
      activated voxels per false positive for each filter set-up. At a significance
      level of 5%, the number of activated voxels was increased up to 41% by using the
      proposed filtering strategy.

PMID- 22484205
TI  - Morphometric gray matter differences of the medial frontal cortex influence the
      Social Simon Effect.
AB  - Interacting with others plays a fundamental role in human life. Although several
      brain regions have recently been associated with complex cognitive control
      processes, surprisingly little is known about the structural correlates
      underlying cognitive control processes involved in social interactions. In the
      present study we used gray matter voxel-based morphometry (VBM) to investigate
      structural brain correlates of individual performance differences in a social
      Simon task. Here, two people share a Simon task, which requires each participant
      to respond to only one of two possible stimuli, rendering the paradigm a go-nogo
      task, so that a Simon effect - known as the Social Simon Effect (SSE) - is
      observable across both participants. Using a whole brain approach, we found that
      inter-individual differences in the SSE are negatively correlated with gray
      matter (GM) volume of the medial frontal cortex (MFC). The present data indicate
      that individuals with larger MFC GM volume were those with better conflict
      resolution in a social Simon task and vice versa. This brain-behavior
      relationship between cognitive control processes and individual GM volume
      differences might help to improve our understanding of social interactions in
      joint task performance.

PMID- 22484206
TI  - Cortical functional connectivity decodes subconscious, task-irrelevant threat
      related emotion processing.
AB  - It is currently unclear to what extent cortical structures are required for and
      engaged during subconscious processing of biologically salient affective stimuli
      (i.e. the 'low-road' vs. 'many-roads' hypotheses). Here we show that cortical
      cortical and cortical-subcortical functional connectivity (FC) contain
      substantially more information, relative to subcortical-subcortical FC (i.e.
      'subcortical alarm' and other limbic regions), that predicts subliminal fearful
      face processing within individuals using training data from separate subjects. A
      plot of classification accuracy vs. number of selected whole-brain FC features
      revealed 92% accuracy when learning was based on the top 8 features from each
      training set. The most informative FC was between right amygdala and precuneus,
      which increased during subliminal fear conditions, while left and right amygdala
      FC decreased, suggesting a bilateral decoupling of this key limbic region during
      processing of subliminal fear-related stimuli. Other informative FC included
      angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC
      that decodes subliminally perceived, task-irrelevant affective stimuli, and
      suggest that cortical structures are actively engaged by and appear to be
      essential for subliminal fear processing.

PMID- 22484207
TI  - Is the evidence for the use of subglottic drainage to prevent ventilated
      associated pneumonia sufficient to change practice?
AB  - This paper critiques the systematic review and meta-analysis of the effect of
      subglottic drainage among patients who received mechanical ventilation.
      Subglottic secretion drainage can reduce bacterial pathogens from entering the
      lower respiratory tract and potentially reduce the occurrence of ventilator
      associated pneumonia. A summary of the systematic review and meta-analysis is
      provided. The critique examines the study's strengths and weaknesses and
      implications for practice are discussed. It is a well-conducted systematic review
      and meta-analysis with few suggestions for improvement. Subglottic secretion
      drainage reduced the incidence of ventilator-associated pneumonia. Several
      studies have shown positive effects of using subglottic drainage but despite the
      evidence, the practice in ICUs is not widespread.

PMID- 22484208
TI  - Haemoglobin hope and glycated haemoglobin: one peak may or may not hide the
      other, depending on the assay.

PMID- 22484209
TI  - Inhibition of P-glycoprotein functionality by vandetanib may reverse cancer cell
      resistance to doxorubicin.
AB  - P-glycoprotein belongs to the ATP binding cassette transporters, responsible for
      the multidrug resistance of cancer cells. These transporters efflux hydrophobic
      drugs outside cells and decrease their therapeutic efficacy. The aim of this
      study was to investigate the effect of vandetanib, an oral tyrosine kinase
      inhibitor of EGFR, VEGFR 2 and RET kinases, on the functionality of P-gp after a
      24h-treatment at therapeutic concentration (2MUM), and its ability to increase
      the cytotoxicity of chemotherapeutic agents in multidrug resistance cancer cells.
      In this study we found that IGROV1-DXR and IGROV1-CDDP cells were resistant to
      doxorubicin and cisplatin respectively, compare to parental cell line IGROV1. The
      parental sensitive and the two resistant cell lines similarly expressed MRP1 and
      did not express BCRP. Moreover, in contrast to the IGROV1 and IGROV1-CDDP cells,
      IGROV1-DXR cell line overexpressed P-gp. Functional activity studies demonstrated
      that MRP1 was not functional and the MDR phenotype in IGROV1-DXR cells was linked
      to P-gp functionality. Results also showed that vandetanib reversed resistance to
      doxorubicin in IGROV1-DXR cells, but not to cisplatin in IGROV1-CDDP cells. After
      24h of treatment, vandetanib increased the accumulation of rhodamine 123 and
      calcein AM, demonstrating a functional inhibition of the transporter. In IGROV1
      DXR cell line, vandetanib reverse resistance to doxorubicin by inhibiting the
      functionality of P-gp. In conclusion, vandetanib should be an option for drug
      combination in patients already developing a P-gp mediated multidrug resistance.

PMID- 22484210
TI  - Ex vivo models to evaluate the role of ocular melanin in trans-scleral drug
      delivery.
AB  - Trans-scleral delivery is nowadays considered as a possible way to deliver drugs
      to the posterior segment of the eye. Despite the potentiality of this
      administration route, there is a lack of fundamental knowledge on the role of the
      numerous barriers involved. The aim of this work was to develop an easy and cheap
      ex vivo method to evaluate the barrier properties of the choroid-Bruch's layer
      and in particular to estimate the role of melanin in drug diffusion through
      ocular tissues. In vitro binding studies were performed to estimate drug affinity
      for melanin; model molecules used were methylene blue, propranolol, levofloxacin
      and methylprednisolone sodium succinate. The ex vivo model set up is based on
      porcine eye bulbs with light blue iris or brown iris. While the choroid of brown
      eyes is dark, the choroid of blue eyes is transparent, due to the absence of
      melanin. Permeation experiments using pigmented and not-pigmented porcine tissues
      gave the opportunity to discriminate between the barrier role of choroid-Bruch's
      membrane as such and the barrier role of melanin. Ex vivo permeation experiments
      can be performed using isolated choroid-Bruch's or the sclera-choroid-Bruch's
      layer. In this last case, it is possible to take into account also the barrier
      role of the sclera that tends to decrease the drug concentration at the
      sclera/choroid interface, thus amplifying the effect of melanin. The data
      obtained in this paper indicate that for some drugs melanin can really represent
      a barrier and the effect can imply a lower drug flux or simply a longer lag time
      depending on the kind of drug and the concentration applied. However, it is a
      saturable barrier, thus its effect can probably be overtaken by high doses or
      multiple administrations. The ex vivo model set up can help to refine
      computational models, to better evaluate the interplay among static, dynamic and
      metabolic barriers. Additionally, since human eyes display a full range of
      pigmentation, the model could also be useful to investigate the possible
      influence of pigmentation phenotype on trans-scleral delivery.

PMID- 22484211
TI  - Need for clarification of data in the recent meta-analysis about 1858 C/T
      Polymorphism of the Protein Tyrosine Phosphatase Nonreceptor 22 Gene and
      Rheumatoid Arthritis Risk.

PMID- 22484213
TI  - Association between MTHFR C677T polymorphism and diabetic nephropathy or diabetes
      mellitus risk: need for clarification of data in a recent meta-analysis.

PMID- 22484214
TI  - Recent advances in researches on the innate immunity of shrimp in China.
AB  - The annual production of shrimp culture in mainland of China has been over one
      million tons for several years. The major cultivated penaeidae species are
      Litopenaeus vannamei, Fenneropenaeus chinensis, Penaeus monodon and Marsupenaeus
      japonicus. Due to the importance of shrimp aquaculture in China, researchers have
      paid more attention to the molecular mechanism of shrimp disease occurrence and
      tried to develop an efficient control strategy for disease. This paper summarizes
      the research progress related to innate immunity of penaeid shrimp made in the
      last decade in Mainland China. Several pattern recognition receptors, such as
      lectin, toll, lipopolysaccharide and beta-1,3-glucan binding protein (LGBP) and
      tetraspanin were identified. The major signal transduction pathways, including
      Toll pathway, IMD pathway, which might be involved in the immune response of
      shrimp, were focused on and most of the components in Toll pathway were
      identified. Also, cellular immune responses such as phagocytosis and apoptosis
      were regarded playing very important roles in anti-WSSV infection to shrimp. The
      molecules involved in the maintenance of the immune homeostasis of shrimp and the
      progress on molecular structure and pathogenic mechanism of WSSV were summarized.
      Therefore, the brief outline about the immune system of shrimp is drawn based on
      the recent data which will help us to understand the immune responses of shrimp
      to different pathogens.

PMID- 22484215
TI  - Proteomics and its applications to aquaculture in China: infection, immunity, and
      interaction of aquaculture hosts with pathogens.
AB  - China is the largest fishery producer worldwide in term of its aquaculture
      output, and plays leading and decisive roles in international aquaculture
      development. To improve aquaculture output further and promote aquaculture
      business development, infectious diseases and immunity of fishes and other
      aquaculture species must be studied. In this regard, aquaculture proteomics has
      been widely carried out in China to get a better understanding of aquaculture
      host immunity and microbial pathogenesis as well as host-pathogen interactions,
      and to identify novel disease targets and vaccine candidates for therapeutic
      interventions. These proteomics studies include development of novel methods,
      assays, and advanced concepts in order to characterize proteomics mechanisms of
      host innate immune defense and microbial pathogenesis. This review article
      summarizes some recently published technical approaches and their applications to
      aquaculture proteomics with an emphasis on the responses of aquaculture animals
      to bacteria, viruses, and other aqua-environmental stresses, and development of
      broadly cross-protective vaccine candidates. The reviewed articles are those that
      have been published in international peer reviewed journals.

PMID- 22484216
TI  - Home accessibility, living circumstances, stage of activity limitation, and
      nursing home use.
AB  - OBJECTIVE: To explore the influence of physical home and social environments and
      disability patterns on nursing home (NH) use. DESIGN: Longitudinal cohort study.
      Self- or proxy-reported perception of home environmental barriers accessibility,
      5 stages expressing the severity and pattern of activities of daily living (ADLs)
      limitations, and other characteristics at baseline were applied to predict NH use
      within 2 years or prior to death through logistic regression. SETTING: General
      community. PARTICIPANTS: Population-based, community-dwelling individuals
      (N=7836; >=70y) from the Second Longitudinal Study of Aging interviewed in 1994
      with 2-year follow-up that was prospectively collected. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: NH use within 2 years. RESULTS: Perceptions of
      home environmental barriers and living alone were both associated with
      approximately 40% increased odds of NH use after adjustment for other factors.
      Compared with those with no limitations at ADL stage 0, the odds of NH use peaked
      for those with severe limitations at ADL stage III (odds ratio [OR]=3.12; 95%
      confidence interval [CI], 2.20-4.41), then declined sharply for those with total
      limitations at ADL stage IV (OR=.96; 95% CI, .33-2.81). Sensitivity analyses for
      missing NH use showed similar results. CONCLUSIONS: Accessibility of home
      environment, living circumstance, and ADL stage represent potentially modifiable
      targets for rehabilitation interventions for decreasing NH use in the aging U.S.
      population.

PMID- 22484217
TI  - How do alternative ways of responding influence 3- and 4-year-olds' performance
      on tests of executive function and theory of mind?
AB  - A total of 69 preschool children were tested on measures of false belief
      understanding (the Unexpected Transfer task), inhibitory control (the Grass/Snow
      task), and strategic reasoning (the Windows task). For each task, children
      indicated their response either by pointing with their index finger or by using a
      nonstandard response mode (pointing with a rotating arrow). The means of
      responding had no effect on children's performance on the Grass/Snow task or on
      the Unexpected Transfer task, although children performed better on the
      Unexpected Transfer task when the key object in the story was removed. In
      contrast, performance on the Windows task was significantly better when children
      pointed with the rotating arrow. A follow-up experiment with 79 preschoolers
      found that this improved performance on the Windows task was sustained even after
      the nonstandard response mode was removed and children again pointed with their
      finger. These findings together suggest that nonstandard response modes do not
      help children to inhibit prepotent pointing responses but may help them to
      formulate response strategies on reasoning tasks by discouraging unreflective
      impulsive responding.

PMID- 22484218
TI  - Groundwater quality and its health impact: An assessment of dental fluorosis in
      rural inhabitants of the Main Ethiopian Rift.
AB  - This study aims to assess the link between fluoride content in groundwater and
      its impact on dental health in rural communities of the Ethiopian Rift. A total
      of 148 water samples were collected from two drainage basins within the Main
      Ethiopian Rift (MER). In the Ziway-Shala basin in particular, wells had high
      fluoride levels (mean: 9.4+/-10.5mg/L; range: 1.1 to 68 mg/L), with 48 of 50
      exceeding the WHO drinking water guideline limit of 1.5mg/L. Total average daily
      intake of fluoride from drinking groundwater (calculated per weight unit) was
      also found to be six times higher than the No-Observed-Adverse-Effects-Level
      (NOAEL) value of 0.06 mg/kg/day. The highest fluoride levels were found in highly
      alkaline (pH of 7 to 8.9) groundwater characterized by high salinity; high
      concentrations of sodium (Na+), bicarbonate (HCO3-), and silica (SiO2); and low
      concentrations of calcium (Ca2+). A progressive Ca2+ decrease along the
      groundwater flow path is associated with an increase of fluoride in the
      groundwater. The groundwater quality problem is also coupled with the presence of
      other toxic elements, such as arsenic (As) and uranium (U). The health impact of
      fluoride was evaluated based on clinical examination of dental fluorosis (DF)
      among local residents using the Thylstrup and Fejerskov index (TFI). In total,
      200 rural inhabitants between the ages of 7 and 40 years old using water from 12
      wells of fluoride range of 7.8-18 mg/L were examined. Signs of DF (TF score of >=
      1) were observed in all individuals. Most of the teeth (52%) recorded TF scores
      of 5 and 6, followed by TF scores of 3 and 4 (30%), and 8.4% had TF scores of 7
      or higher. Sixty percent of the teeth exhibited loss of the outermost enamel.
      Within the range of fluoride contents, we did not find any correlation between
      fluoride content and DF. Finally, preliminary data suggest that milk intake has
      contributed to reducing the severity of DF. The study highlights the apparent
      positive role of milk on DF, and emphasizes the importance of nutrition in
      management efforts to mitigate DF in the MER and other parts of the world.

PMID- 22484219
TI  - The urban rise and fall of air lead (Pb) and the latent surge and retreat of
      societal violence.
AB  - We evaluate air Pb emissions and latent aggravated assault behavior at the scale
      of the city. We accomplish this by regressing annual Federal Bureau of
      Investigation aggravated assault rate records against the rise and fall of annual
      vehicle Pb emissions in Chicago (Illinois), Indianapolis (Indiana), Minneapolis
      (Minnesota), San Diego (California), Atlanta (Georgia), and New Orleans
      (Louisiana). Other things held equal, a 1% increase in tonnages of air Pb
      released 22 years prior raises the present period aggravated assault rate by
      0.46% (95% CI, 0.28 to 0.64). Overall our model explains 90% of the variation in
      aggravated assault across the cities examined. In the case of New Orleans, 85% of
      temporal variation in the aggravated assault rate is explained by the annual rise
      and fall of air Pb (total=10,179 metric tons) released on the population of New
      Orleans 22 years earlier. For every metric ton of Pb released 22 years prior, a
      latent increase of 1.59 (95% CI, 1.36 to 1.83, p<0.001) aggravated assaults per
      100,000 were reported. Vehicles consuming fuel containing Pb additives
      contributed much larger quantities of Pb dust than generally recognized. Our
      findings along with others predict that prevention of children's lead exposure
      from lead dust now will realize numerous societal benefits two decades into the
      future, including lower rates of aggravated assault.

PMID- 22484220
TI  - Investigation of OCP-triggered dissipation of excitation energy in PSI/PSII-less
      Synechocystis sp. PCC 6803 mutant using non-linear laser fluorimetry.
AB  - In order to prevent photodestruction by high light, photosynthetic organisms have
      evolved a number of mechanisms, known as non-photochemical quenching (NPQ), that
      deactivate the excited states of light harvesting pigments. Here we investigate
      the NPQ mechanism in the cyanobacterium Synechocystis sp. PCC 6803 mutant
      deficient in both photosystems. Using non-linear laser fluorimetry, we have
      determined molecular photophysical characteristics of phycocyanin and spectrally
      distinct forms of allophycocyanin for the cells in non-quenched and quenched
      states. Our analysis of non-linear fluorescence characteristics revealed that NPQ
      activation leads to an ~2-fold decrease in the relaxation times of both
      allophycocyanin fluorescence components, F660 and F680, and a 5-fold decrease in
      the effective excitation cross-section of F680, suggesting an emergence of a
      pathway of energy dissipation for both types of allophycocyanin. In contrast, NPQ
      does not affect the rates of singlet-singlet exciton annihilation. This indicates
      that, upon NPQ activation, the excess excitation energy is transferred from
      allophycocyanins to quencher molecules (presumably 3'hydroxyechinenone in the
      orange carotenoid protein), rather than being dissipated due to conformational
      changes of chromophores within the phycobilisome core. Kinetic measurements of
      fluorescence quenching in the Synechocystis mutant revealed the presence of
      several stages in NPQ development, as previously observed in the wild type.
      However, the lack of photosystems in the mutant enhanced the magnitude of NPQ as
      compared to the wild type, and allowed us to better characterize this process.
      Our results suggest a more complex kinetics of the NPQ process, thus clarifying a
      multistep model for the formation of the quenching center.

PMID- 22484221
TI  - Heme A biosynthesis.
AB  - Respiration in plants, most animals and many aerobic microbes is dependent on
      heme A. This is a highly specialized type of heme found as prosthetic group in
      cytochrome a-containing respiratory oxidases. Heme A differs structurally from
      heme B (protoheme IX) by the presence of a hydroxyethylfarnesyl group instead of
      a vinyl side group at the C2 position and a formyl group instead of a methyl side
      group at position C8 of the porphyrin macrocycle. Heme A synthase catalyzes the
      formation of the formyl side group and is a poorly understood heme-containing
      membrane bound atypical monooxygenase. This review presents our current
      understanding of heme A synthesis at the molecular level in mitochondria and
      aerobic bacteria. This article is part of a Special Issue entitled:
      Biogenesis/Assembly of Respiratory Enzyme Complexes.

PMID- 22484223
TI  - Approach to the epidemiology of venomous bites in Spain.
AB  - This review presents a geographic distribution of the three autochthonous
      venomous snake species, which are the only viperids present in Spain, among the
      Iberian fauna: Vipera aspid; Vipera seoianei and Vipera latasti. This is followed
      by a detailed descriptive analysis of hospital care provided to patients admitted
      into hospital due to venomous bites, in the period from 1997 to 2009, using the
      data from the Spanish hospital discharge registry database. This analysis reveals
      that in Spain, during this period, 1649 cases were recorded, which means that
      hospital care was required for more than one hundred cases per year, of which
      nearly 1% of the cases resulted in death. Cases were recorded in all the
      Autonomous communities, but more than half (54, 14%) were concentrated in the
      following four regions: Cataluna, Castilla and Leon, Galicia and Andalucia. It is
      notable that this concentration of cases is not associated only with the
      population demographics of the community, but is also the result of the
      concurrence of very diverse factors of exposure including: habitat of venomous
      fauna, volume of rural population, farming activities, and practice of outdoor
      leisure activities. We also carried out a gross economic calculation for the use
      of hospital resources by each snakebite case requiring hospital care in Spain,
      which provided us with an approximate figure of 2000? per case.

PMID- 22484222
TI  - MicroRNAs in inner ear biology and pathogenesis.
AB  - MicroRNAs (miRNA) are a group of small noncoding RNAs that regulate gene
      expression. The discovery of these small RNAs has added a new layer of complexity
      to molecular biology. Every day, new advances are being made in understanding the
      biochemistry and genetics of miRNAs and their roles in cellular function and
      homeostasis. Studies indicate diverse roles for miRNAs in inner ear biology and
      pathogenesis. This article reviews recent developments in miRNA research in the
      field of inner ear biology. A brief history of miRNA discovery is discussed, and
      their genomics and functional roles are described. Advances in the understanding
      of miRNA involvement in inner ear development in the zebrafish and the mouse are
      presented. Finally, this review highlights the potential roles of miRNAs in
      genetic hearing loss, hair cell regeneration, and inner ear pathogenesis
      resulting from various pathological insults.

PMID- 22484224
TI  - Determination of swainsonine in the endophytic Undifilum fungi by high
      performance liquid chromatography with evaporative light-scattering detector.
AB  - Endophytic Undifilum oxytropis found within toxic locoweeds (Astragalus and
      Oxytropis spp.) produces the indolizidine alkaloid swainsonine, which is
      responsible for locoism in grazing animals. The aim of the current study is to
      establish an easy and accurate method for the determination of swainsonine in the
      endophytic Undifilum fungi. High-performance liquid chromatography (HPLC) with
      evaporative light-scattering detector (ELSD) was used for the assay of
      swainsonine in this study for the first time. The HPLC conditions were Waters
      XBridge hydrophilic interaction liquid chromatography column using acetonitrile-5
      mM ammonium acetate (1:1, vol/vol) containing 0.02% (vol/vol) aqueous ammonium
      hydroxide as mobile phase at a flow rate of 0.5 mL/min. ELSD conditions were
      optimized at nebulizer-gas flow rate of 25 psi and drift tube temperature of 55 
      degrees C. The method was validated to achieve the satisfactory precision and
      recovery, and the calibration range was 15.625-250 MUg/mL. Application of the
      developed analytical procedure to determine swainsonine content in the endophytic
      Undifilum fungi samples ensured its suitability for the routine analysis of
      swainsonine.

PMID- 22484225
TI  - Functional plasticity in human FOXP3(+) regulatory T cells: implications for cell
      based immunotherapy.
AB  - CD4(+) regulatory T (T(reg)) cells expressing the Foxp3 transcription factor are
      critical for the induction and maintenance of immune homeostasis and self
      tolerance in experimental rodents and humans. Foxp3(+) T(reg) cells constitute a
      unique CD4(+) T cell subset with potent suppressive properties, and their
      functional and homeostatic stability is essential to ensure dominant tolerance in
      a variety of inflammatory settings. Interestingly, recent evidence points to the
      inherent potential of T(reg) cells to adapt to environmental cues and
      consequently manifest functional plasticity by downregulating Foxp3 expression,
      and reprogramming into inflammatory T cells. The potential for suppressive
      Foxp3(+) T(reg) cells to undergo functional plasticity and gain inflammatory
      properties is of concern when one considers the ex vivo manipulation or
      generation of such cells for therapeutic purposes in various autoimmune or
      chronic inflammatory disorders. Collectively, the experimental evidence
      accumulated so far on the modalities of this plasticity can provide valuable cues
      as to strategies that can be implemented to control it, potentially allowing to
      facilitate the path to efficient and safe T(reg)-based therapy.

PMID- 22484226
TI  - Susceptibility to cervical cancer: an overview.
AB  - Cervical cancer is the second most common cancer in females worldwide. It is well
      established that Human Papillomavirus (HPV) infections play a critical role in
      the development of cervical cancer. However, a large number of women infected
      with oncogenic HPV types will never develop cervical cancer. Thus, there are
      several external environment and genetic factors involved in the progression of a
      precancerous lesion to invasive cancer. In this review article, we addressed
      possible susceptible phenotypes to cervical cancer, focusing on host genome and
      HPV DNA variability, multiple HPV infections, co-infection with other agents,
      circulating HPV DNA and lifestyle.

PMID- 22484228
TI  - Inhalable sustained-release formulation of long-acting vasoactive intestinal
      peptide derivative alleviates acute airway inflammation.
AB  - The present study was undertaken to develop a respirable sustained-release powder
      (RP) formulation of long-acting VIP derivative, [Arg(15, 20, 21), Leu(17)]-VIP
      GRR (IK312532), using PLGA nanospheres (NS) with the aim of improving the
      duration of action. NS formulation of IK312532 (IK312532/NS) was prepared by an
      emulsion solvent diffusion method in oil, and a mixture of the IK312532/NS and
      erythritol was jet-milled and mixed with lactose carrier to obtain the
      IK312532/NS-RP. Physicochemical properties were characterized focusing on
      appearance, particle size, and drug release, and in vivo pharmacological effects
      were assessed in antigen-sensitized rats. The IK312532/NS with a diameter of 140
      nm showed a biphasic release pattern in distilled water with ca. 20% initial
      burst for 30 min and a sustained slow release up to ca. 55% for 24h. Laser
      diffraction analysis demonstrated that IK312532/NS-RP had fine dispersibility and
      suitable particle size for inhalation. In antigen-sensitized rats, insufflated
      IK312532/NS-RP (10 MUg of IK312532/rat) could suppress increases of granulocyte
      recruitment and myeloperoxidase in pulmonary tissue for up to 24h after antigen
      challenge, although IK312532-RP at the same dose was less effective with limited
      duration of action. From these findings, newly prepared IK312532/NS-RP might be
      of clinical importance in improving duration of action and medication compliance
      for treatment of airway inflammatory diseases.

PMID- 22484227
TI  - Localization of calcitonin receptor-like receptor (CLR) and receptor activity
      modifying protein 1 (RAMP1) in human gastrointestinal tract.
AB  - Calcitonin gene-related peptide (CGRP) exerts its diverse effects on
      vasodilation, nociception, secretion, and motor function through a heterodimeric
      receptor comprising of calcitonin receptor-like receptor (CLR) and receptor
      activity-modifying protein 1 (RAMP1). Despite the importance of CLR.RAMP1 in
      human disease, little is known about its distribution in the human
      gastrointestinal (GI) tract, where it participates in inflammation and pain. In
      this study, we determined that CLR and RAMP1 mRNAs are expressed in normal human
      stomach, ileum and colon by RT-PCR. We next characterized antibodies that we
      generated to rat CLR and RAMP1 in transfected HEK cells. Having characterized
      these antibodies in vitro, we then localized CLR-, RAMP1-, CGRP- and intermedin
      immunoreactivity (IMD-IR) in various human GI segments. In the stomach, nerve
      bundles in the myenteric plexus and nerve fibers throughout the circular and
      longitudinal muscle had prominent CLR-IR. In the proximal colon and ileum, CLR
      was found in nerve varicosities of the myenteric plexus and surrounding
      submucosal neurons. Interestingly, CGRP expressing fibers did not co-localize,
      but were in close proximity to CLR. However, CLR and RAMP1, the two subunits of a
      functional CGRP receptor were clearly localized in myenteric plexus, where they
      may form functional cell-surface receptors. IMD, another member of calcitonin
      peptide family was also found in close proximity to CLR, and like CGRP, did not
      co-localize with either CLR or RAMP1 receptors. Thus, CGRP and IMD appear to be
      released locally, where they can mediate their effect on their receptors
      regulating diverse functions such as inflammation, pain and motility.

PMID- 22484229
TI  - Morphological and molecular characterisation of Echinococcus granulosus from goat
      isolates in Iran.
AB  - Hydatidosis is considered to be an important economic and human public health
      problem in Iran, where a variety of animals act as intermediate hosts. There is
      limited information about the genotypes of Echinococcus granulosus in goats. In
      this study, 20 isolates of E. granulosus obtained from goats were characterised
      by mitochondrial DNA sequencing and morphology of the metacestode. The
      mitochondrial cytochrome oxidase 1 sequences were evaluated, and the sequence
      analysis indicated two genotypes within the isolates. 17 samples were identified
      as G1 strain, and 3 isolates were identified as G6 strain. The results of the
      morphological studies support the findings of the molecular studies. Two types of
      rostellar hooks were observed in the goat isolates, in agreement with the strain
      identification. Type 1 hooks were morphologically similar to those of the common
      sheep strains, whereas the dimensions of the hooks in type 2 were similar to
      those normally found in the camel strain. The morphological results suggest that
      Echinococcus of goat origin is phenotypically similar to either the sheep (G1) or
      the camel (G6) strains. Further, these results suggest that the transmission of
      the G1 genotype between sheep and goats seems to be the predominant mode of
      transmission, but further work is required to verify this.

PMID- 22484230
TI  - Hereditary characteristic of isolated congenital vomer aplasia.
AB  - Malformation of the inner nose is often found in conjunction with different types
      of cleft palate or may be seen with severe and complex craniofacial anomalies.
      Among such malformations, however, isolated vomer aplasia is rarely reported in
      the literature. This study sets forth our findings that congenital vomeral defect
      of the nasal septum is an isolated disorder with hereditary characteristics.
      Between 2001 and 2009, nine cases of isolated congenital vomeral bone defect were
      detected on endoscopic examination of patients referred to our clinic with nasal
      and otologic complaints. The files of these patients were reviewed and vomer
      aplasia was identified as an isolated hereditary condition with concomitant
      sinonasal symptoms. The defect of the posteroinferior part of the nasal septum
      was defined as a genetic disease presenting with no significant medical problems.
      Chromosomal analysis of these patients may help to reveal the relationship of
      this anomaly with different malformations of the maxillofacial complex.

PMID- 22484231
TI  - Timing of palate repair affecting growth in complete unilateral cleft lip and
      palate.
AB  - OBJECTIVE: To evaluate the facial morphology characteristics of patients with
      complete unilateral cleft lip and palate (UCCLPs) who had undergone cleft palate
      repair at different times. DESIGN: This study included 46 nonsyndromic UCCLPs and
      38 age and sex matched non-cleft patients. 35 cephalometric measurements were
      used to evaluate the facial morphology. Student's t-test, one-way ANOVA and rank
      sum tests were used for comparison. Significant difference was defined at 95%
      level. RESULTS: The data showed that UCCLPs who had palatoplasty between 7 and 12
      years had greater PMP-A, PMP-ANS, Ba-ANS, Ba-A, Ba-N-ANS than those operated on
      before 4 years of age, and UCCLPs who had palatoplasty at 4-12 years had smaller
      Y-axis angle than those operated on before 4 years of age. CONCLUSIONS: The
      maxillary sagittal length increased gradually as von Langenbeck repair was
      delayed. UCCLPs who underwent palate repair using von Langenbeck technique at 4
      12 years had a more protrusive maxilla and less clockwise rotated mandible than
      those repaired before 4 years. UCCLPs operated using the von Langenbeck technique
      at 4-12 years had better head-face morphology than those operated on before 4
      years. There was no difference in facial morphology among UCCLPs with palate
      repair at 4-12 years.

PMID- 22484232
TI  - New Triatoma virus hosts in wild habitats of Argentina.
AB  - Triatoma virus (TrV), a member of the Dicistroviridae family, replicates in
      intestinal epithelial cells, causing delayed development and death of infected
      individuals. The aims of this study were to find naturally infected species of
      Triatominae in the wild in the region endemic for Chagas disease and analyze and
      compare the sequence diversity of TrV obtained from different Triatominae. A
      total of 253 Triatominae belonging to 10 species were captured by active or
      passive collection. Three new sequences were obtained from Triatoma infestans,
      Triatoma delpontei and Psammolestes coreodes and the analysis revealed that these
      sequences were very similar. Ps. coreodes is a new host for TrV.

PMID- 22484233
TI  - Susceptibility to infection and pathogenicity of White Spot Disease (WSD) in non
      model crustacean host taxa from temperate regions.
AB  - Despite almost two decades since its discovery, White Spot Disease (WSD) caused
      by White Spot Syndrome Virus (WSSV) is still considered the most significant
      known pathogen impacting the sustainability and growth of the global penaeid
      shrimp farming industry. Although most commonly associated with penaeid shrimp
      farmed in tropical regions, the virus is also able to infect, cause disease and
      kill a wide range of other decapod crustacean hosts from temperate regions,
      including lobsters, crabs, crayfish and shrimp. For this reason, WSSV has
      recently been listed in European Community Council Directive 2006/88. Using
      principles laid down by the European Food Safety Authority (EFSA) we applied an
      array of diagnostic approaches to provide a definitive statement on the
      susceptibility to White Spot Syndrome Virus (WSSV) infection in seven
      ecologically or economically important crustacean species from Europe. We chose
      four marine species: Cancer pagurus, Homarus gammarus, Nephrops norvegicus and
      Carcinus maenas; one estuarine species, Eriocheir sinensis and two freshwater
      species, Austropotamobius pallipes and Pacifastacus leniusculus. Exposure trials
      based upon natural (feeding) and artificial (intra-muscular injection) routes of
      exposure to WSSV revealed universal susceptibility to WSSV infection in these
      hosts. However, the relative degree of susceptibility (measured by progression of
      infection to disease, and mortality) varied significantly between host species.
      In some instances (Type 1 hosts), pathogenesis mimicked that observed in penaeid
      shrimp hosts whereas in other examples (Types 2 and 3 hosts), infection did not
      readily progress to disease, even though hosts were considered as infected and
      susceptible according to accepted principles. Results arising from challenge
      studies are discussed in relation to the potential risk posed to non-target hosts
      by the inadvertent introduction of WSSV to European waters via trade.
      Furthermore, we highlight the potential for susceptible but relatively resistant
      hosts to serve as models to investigate natural mitigation strategies against
      WSSV in these hosts. We speculate that these non-model hosts may offer a unique
      insight into viral handling in crustaceans.

PMID- 22484234
TI  - Detection of p53 gene point mutation using sequence-specific molecularly
      imprinted PoPD electrode.
AB  - An amperometric sequence-specific molecularly imprinted single-stranded
      oligodeoxyribonucleotide (ss-ODN) biosensor was fabricated and characterised in
      this study. Using ss-ODN as the template and o-phenylenediamine as the functional
      monomer, the ODN biosensor was fabricated by an electropolymerisation process on
      an indium-tin oxide (ITO) coated glass substrate. The template ss-ODN was washed
      out of the ss-ODN/poly(o-phenylenediamine)(PoPD)/ITO electrode using sterilised
      basic ethanol-water. The resulting ss-ODN imprinted PoPD/ITO electrode was
      characterised using Fourier transform infrared spectroscopy (FTIR), scanning
      electron microscopy (SEM) and cyclic voltammetry (CV). The amperometric
      responses, i.e., Deltai as a function of the target ss-ODN concentration was
      studied. The biosensor using ss-ODN imprinted PoPD/ITO as the working electrode
      showed a linear Delta current response to the target ss-ODN concentration within
      the range of 0.01-300 fM. The biosensor showed a sensitivity of 0.62 MUA/fM, with
      a response time of 14s. The present novel molecularly imprinted ss-ODN biosensor
      could greatly benefit in terms of cost-effectiveness, storage stability, ultra
      sensitivity and selectivity together with the potential for improved commercial
      genetic sensors.

PMID- 22484235
TI  - DNA electrochemical biosensor based on thionine-graphene nanocomposite.
AB  - A novel protocol for development of DNA electrochemical biosensor based on
      thionine-graphene nanocomposite modified gold electrode was presented. The
      thionine-graphene nanocomposite layer with highly conductive property was
      characterized by scanning electron microscopy, transmission electron microscopy,
      cyclic voltammetry and electrochemical impedance spectroscopy. An amino
      substituted oligonucleotide probe was covalently grafted onto the surface of the
      thionine-graphene nanocomposite by the cross-linker glutaraldehyde. The
      hybridization reaction on the modified electrode was monitored by differential
      pulse voltammetry analysis using an electroactive intercalator daunomycin as the
      indicator. Under optimum conditions, the proposed biosensor exhibited high
      sensitivity and low detection limit for detecting complementary oligonucleotide.
      The complementary oligonucleotide could be quantified in a wide range of 1.0 *
      10(-12) to 1.0 * 10(-7)M with a good linearity (R(2)=0.9976) and a low detection
      limit of 1.26 * 10(-13)M (S/N=3). In addition, the biosensor was highly selective
      to discriminate one-base or two-base mismatched sequences.

PMID- 22484236
TI  - Neurosecretory cell-based biosensor: monitoring secretion of adrenal chromaffin
      cells by local extracellular acidification using light-addressable potentiometric
      sensor.
AB  - Vesicular exocytosis plays an important role in many physiological processes. The
      dense-core vesicles release of chromaffin cells is a suitable model for the
      presynaptic process in neurosecretory cells. In this study, light-addressable
      potentiometric sensor (LAPS) was introduced as a label-free recording method for
      vesicle release by the local extracellular acidification. The chromaffin cells
      are directly cultured on the sensor surface. After cells and LAPS hybrid system
      is established, the events of vesicular exocytosis are recorded. Protons stored
      in the vesicles and co-released with transmitters, induced a brief acidic shifts
      in the cell-sensor cleft. Under the stimulation of the KCl and acetylcholine
      (Ach), the signals presented the different amplitude and exocytosis rate, and
      reflected the specific features of the exocytosis. The result indicates that
      neurosecretory cell-based biosensor will provide a useful platform for
      neurosecretion mechanism research by monitoring the exocytotic activities with
      extracellular acidification sensing.

PMID- 22484237
TI  - Structure of Escherichia coli OmpF porin from lipidic mesophase.
AB  - Outer membrane protein F, a major component of the Escherichia coli outer
      membrane, was crystallized for the first time in lipidic mesophase of monoolein
      in novel space groups, P1 and H32. Due to ease of its purification and
      crystallization OmpF can be used as a benchmark protein for establishing membrane
      protein crystallization in meso, as a "membrane lyzozyme". The packing of porin
      trimers in the crystals of space group H32 is similar to natural outer membranes,
      providing the first high-resolution insight into the close to native packing of
      OmpF. Surprisingly, interaction between trimers is mediated exclusively by
      lipids, without direct protein-protein contacts. Multiple ordered lipids are
      observed and many of them occupy identical positions independently of the space
      group, identifying preferential interaction sites of lipid acyl chains. Presence
      of ordered aliphatic chains close to a positively charged area on the porin
      surface suggests a position for a lipopolysaccharide binding site on the surface
      of the major E. coli porins.

PMID- 22484238
TI  - Crystal structure of a mono- and diacylglycerol lipase from Malassezia globosa
      reveals a novel lid conformation and insights into the substrate specificity.
AB  - Most lipases contain a lid domain to shield the hydrophobic binding site from the
      water environment. The lid, mostly in helical form, can undergo a conformational
      change to expose the active cleft during the interfacial activation. Here we
      report the crystal structures of Malassezia globosa LIP1 (SMG1) at 1.45 and 2.60
      A resolution in two crystal forms. The structures present SMG1 in its closed
      form, with a novel lid in loop conformation. SMG1 is one of the few members in
      the fungal lipase family that has been found to be strictly specific for mono-
      and diacylglycerol. To date, the mechanism for this substrate specificity remains
      largely unknown. To investigate the substrate binding properties, we built a
      model of SMG1 in open conformation. Based on this model, we found that the two
      bulky hydrophobic residues adjacent to the catalytic site and the N-terminal
      hinge region of the lid both may act as steric hindrances for triacylglycerols
      binding. These unique structural features of SMG1 will provide a better
      understanding on the substrate specificity of mono- and diacylglycerol lipases
      and a platform for further functional study of this enzyme.

PMID- 22484239
TI  - Cost effective and time efficient measurement of CD4, CD8, major
      histocompatibility complex Class II, and macrophage antigen expression in the
      lungs of chickens.
AB  - Cells expressing CD4, CD8, major histocompatibility complex (MHC) Class II, and
      macrophage biomarkers in lungs of chickens were quantified by measuring total
      area of antigen expressed using imageJ, a software program developed at the
      National Institutes of Health and available at no cost. The procedures reported
      here were rapid, and reproducible. Total area of antigen expressed had positive
      correlation with manual counts of cells expressing CD4 and CD8 biomarkers after
      inoculation with serotype 1 Marek's disease virus (MDV) vaccines. Visual
      inspection and overlays prepared from outlines of cells counted by imageJ
      confirmed agreement between antigen expression and area measured. Total area
      measured was not dependent on time of image acquisition from randomly selected
      fields from the same slides. Total area values were not computer specific, but
      acquisition of the original images required standardization of microscope used
      and camera setup. All steps in the process from sample collection through
      sectioning, staining, and image acquisition must be standardized as much as
      possible. Chickens infected with a very virulent+ (vv(+)) isolate of MDV (648A)
      had increased CD4, CD8, MHC Class II, and macrophage biomarker expression
      compared to noninfected control chickens at 10 days post infection, but variable
      responses depending on the specific biomarker measured at 3 and 5 days post
      infection. The procedure described here is faster and more reproducible than
      manual counting in cases (CD4 and CD8) where the number of positive cells is low
      enough for manual counts. Manual counting is not possible with MHC Class II and
      macrophage antigens nor when CD4(+) cells are present in large numbers following
      proliferation to tumors, thus subjective systems are used for scoring in these
      conditions. Using imageJ as described eliminates the need for subjective and less
      reproducible methods for measuring expression of these antigens.

PMID- 22484240
TI  - Physician characteristics and beliefs associated with use of pelvic examinations
      in asymptomatic women.
AB  - OBJECTIVE: To examine physicians' beliefs about the pelvic examination and
      identify physician characteristics associated with routine use of this procedure
      in the United States. METHODS: A total of 1250 United States family/general
      practitioners, internists, and obstetrician/gynecologists who participated in the
      2009 DocStyles survey completed questions on beliefs regarding the utility of
      routine pelvic examinations for cancer screening. The survey also asked
      participants how often they performed this procedure as part of a well-woman
      exam, to screen for ovarian and other gynecologic cancers, to screen for sexually
      transmitted infections, and as a prerequisite for prescribing hormonal
      contraception. RESULTS: A total of 68.0% of obstetrician/gynecologists, 39.2% of
      family/general practitioners, and 18.7% of internists reported routinely
      performing pelvic examinations for all the purposes examined (<0.001). Adjusted
      analyses revealed that the factors most strongly associated with use of pelvic
      examinations for all purposes were being an obstetrician/gynecologist (odds ratio
      8.5; 95% confidence interval 5.8-12.6) and believing that this procedure is
      useful to screen for gynecologic cancers (odds ratio 3.8; 95% confidence interval
      2.6-5.5). CONCLUSION: Misconceptions about the utility of pelvic examinations to
      screen for gynecologic cancers are common. More effective strategies to change
      physicians' beliefs regarding the value of performing pelvic examinations in
      asymptomatic women are needed.

PMID- 22484241
TI  - The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL
      10, RP105 or the kinase activity of RIPK2.
AB  - The anti-inflammatory actions of IL-4 in activated human monocytes may reflect
      transcriptional regulation of genes involved in TLR signaling pathways. Tailored
      gene arrays were conducted to profile the expression of 84 genes central to TLR
      mediated signal transduction in human monocytes treated with the TLR4 ligand,
      LPS, with or without IL-4. In the first 3h, IL-4 down-regulated mRNA levels of
      LPS-induced inflammatory cytokines and chemokines, without altering mRNA levels
      of TLRs, TLR-related signaling molecules or multiple transcription factors. The
      down-regulation of inflammatory genes by IL-4 was preceded by an early up
      regulation of IL-10 mRNA and protein and mRNA for receptor-interacting serine
      threonine kinase 2 (RIPK2), the TLR homolog, RP105, and c-Maf, a transcription
      factor required for IL-10 gene expression. However, IL-4 still suppressed LPS
      induced TNFalpha production in bone-marrow derived macrophages from IL10(-/-)
      mice, and in the presence of a neutralizing antibody to IL-10 in human monocytes.
      The up-regulation of RIPK2 and RP105 mRNA by IL-4 occurred independently of IL
      10. IL-4 maintained the ability to suppress LPS-induced TNFalpha and enhance IL
      10 production in the presence of RIPK2 kinase inhibitors. Further, IL-4 failed to
      up-regulate expression of RP105 at the cell surface. In conclusion, the anti
      inflammatory actions of IL-4 occur independently of IL-10, RP105, and the kinase
      activity of RIPK2.

PMID- 22484242
TI  - Expansion of CD14+CD16+ monocytes producing TNF-alpha in complication-free
      diabetes type 1 juvenile onset patients.
AB  - We concentrated on the complication-free phase of juvenile onset type 1 diabetes
      mellitus (T1DM) searching for associations between concentration of inflammatory
      factors TNF-alpha, CRP and VEGF and two monocyte subsets the CD14(++)CD16(-) and
      CD14(+)CD16(+). We analysed a randomly selected group of 150 patients without
      complications (disease duration 2.74 +/- 2.51 years) at the start of the project
      and 5 years later. They were compared with 24 patients with retinopathy (6.53 +/-
      3.39 years of disease) and 30 healthy volunteers. Our results indicate that in
      the complication-free period the concentration of TNF-alpha significantly
      increased and continued to increase after retinopathy was established. After 5
      years the percentage and absolute number of CD14(+)CD16(+) monocytes doubled in
      complication-free patients. Our study indicates that the size of CD14(+)CD16(+)
      monocyte subset may be used alternatively to CRP values as an indicator of
      inflammation grade. Our results imply the necessity of trials using anti-TNF
      alpha therapy in the complication-free phase of the disease.

PMID- 22484243
TI  - The relationship of cytomegalovirus (CMV) infection with circulatory IFN-alpha
      levels and IL-7 receptor alpha expression on CD8+ T cells in human aging.
AB  - The IL-7 receptor alpha (IL-7Ralpha) is the high affinity receptor for IL-7 which
      is essential for T cell homeostasis. We recently reported an age-associated
      expansion of human effector memory (EM) CD8(+) T cells expressing IL-7Ralpha low
      (IL-7Ralpha(low)), which could be detrimental to hosts by occupying
      "immunological space". We investigated the potential mechanisms for this
      phenomenon, focusing on cytomegalovirus (CMV) infection and INF-alpha. In the
      elderly (age >= 65), CMV infection was associated with a decreased frequency of
      naive CD8(+) T cells as well as with an increased frequency of total EM and IL
      7Ralpha(low) EM CD8(+) T cells. However, in the young (age <= 40), this viral
      infection was associated only with an increased frequency of IL-7Ralpha(low) EM
      CD8(+) T cells. There was no association found between CMV immune status and
      plasma levels of IFN-alpha. In CMV-infected young and elderly people, INF-alpha
      levels had no correlation with the frequency of IL-7Ralpha(low) EM CD8(+) T cells
      although this cytokine levels correlated with the frequency of IL-7Ralpha(low)
      CD45RA(+) EM CD8(+) T cells in CMV-uninfected elderly people. Our findings
      suggest that the effect of CMV infection on the frequency of CD8(+) T cell
      subsets may begin with IL-7Ralpha(low) EM CD8(+) T cells and spread to other
      subsets with aging. Also, IFN-alpha could be associated with the expansion of IL
      7Ralpha(low) CD45RA(+) EM CD8(+) T cells in the CMV-uninfected elderly.

PMID- 22484244
TI  - Use of the T-SPOT.TB assay to screen latent tuberculosis infection among the TB
      contacts in Shanghai, China.
AB  - BACKGROUND: There is limited information on the prevalence of latent tuberculosis
      infection (LTBI) and the risk factors among contacts of pulmonary TB, which might
      contribute significantly to TB burden and therefore become the major concern for
      TB control in Shanghai, China. METHODS: A total of 45 diagnosed TB patients from
      each of 7 Shanghai districts were chosen and approximately 3 contacts per case
      were randomly selected. A structured questionnaire was used to acquire socio
      demographic information and to assess the degree of exposure to index cases. LTBI
      screening was performed by T-SPOT.TB assay. RESULTS: Of 969 enrolled contacts,
      39% were men, average age was 45 +/- 19.1 years, and 76.3% were household
      contacts. LTBI was identified in 29.6% of subjects. Those contacting smear
      positive TB patients were 2.24 times (95%CI, 1.586-3.162) more likely to develop
      LTBI than those otherwise; household contact significantly increased the
      likelihood of LTBI by 1.52 times (95%CI, 1.061-2.180). Furthermore, among
      household contacts, the risk of LTBI was higher in spouses and first-degree
      relatives and increased with age and contact duration. CONCLUSIONS: A high
      prevalence of LTBI was observed among the TB contacts in Shanghai, highlighting
      the need of intervention among the household contacts and those contacting smear
      positive TB patients.

PMID- 22484245
TI  - Treatment of radiocarpal degenerative osteoarthritis by radioscapholunate
      arthrodesis: long-term follow-up.
AB  - Radioscapholunate arthrodesis is the treatment of choice for symptomatic,
      degenerative radioscapholunate osteoarthritis. We report on three patients after
      radioscapholunate arthrodesis with a follow-up of 22-28 years. There were no
      short-term postoperative complications; range of motion and strength were stable.
      All three patients showed radiological evidence of progressive, but clinically
      asymptomatic midcarpal osteoarthritis. The conversion rate for radioscapholunate
      to panarthrodesis of the wrist is reported at 31% with follow-ups of more than
      five years, invariably due to either non-union, or progressive, symptomatic
      midcarpal osteoarthritis. Primary excision of the distal pole of the scaphoid
      during radioscapholunate arthrodesis probably plays an important role in avoiding
      these conditions in the long-term. This measure allows a residual range of motion
      more than previously believed; considering that the dart thrower's motion is the
      physiological axis of wrist motion.

PMID- 22484246
TI  - Successful thumb reconstruction after tumor resection by immediate toe transfer
      in a 67-year-old patient: case report and literature review.
AB  - Age is a limiting factor for microsurgery. We report the case of a 67-year-old
      patient with a malignant tumor on the right thumb, treated by amputation and
      immediate reconstruction by partial transfer of the hallux, with an excellent
      result, but venous swelling at the fourth day that required a controlled bleeding
      for 3 days. In the light of this observation, we think that there is no age limit
      for reconstruction of a thumb by toe transfer, either cosmetically or
      functionally.

PMID- 22484247
TI  - Bacteriohemerythrin bolsters the activity of the particulate methane
      monooxygenase (pMMO) in Methylococcus capsulatus (Bath).
AB  - Recently, a native bacteriohemerythrin (McHr) has been identified in
      Methylococcus capsulatus (Bath). Both the particulate methane monooxygenase
      (pMMO) and McHr are over-expressed in cells of this bacterium when this strain of
      methanotroph is cultured and grown under high copper to biomass conditions. It
      has been suggested that the role of the McHr is to provide a shuttle to transport
      dioxygen from the cytoplasm of the cell to the intra-cytoplasmic membranes for
      consumption by the pMMO. Indeed, McHr enhances the activity of the pMMO when pMMO
      enriched membranes are used to assay the enzyme activity. We find that McHr can
      dramatically improve the activity of pMMO toward the epoxidation of propylene to
      propylene oxide. The maximum activity is observed at a pMMO to McHr concentration
      ratio of 4:1, where we have obtained specific activities of 103.7nmol propylene
      oxide/min/mg protein and 122.8nmol propylene oxide/min/mg protein at 45 degrees C
      when the turnover is driven by NADH and duroquinol, respectively. These results
      are consistent with the suggestion that the bacterium requires McHr to deliver
      dioxygen to the pMMO in the intra-cytoplasmic membranes to accomplish efficient
      catalysis of methane oxidation when the enzyme is over-expressed in the cells.

PMID- 22484248
TI  - EPR and potentiometric studies of copper(II) binding to nicotinamide adenine
      dinucleotide (NAD+) in water solution.
AB  - Coordination of Cu(II) by nicotinamide adenine dinucleotide (NAD(+)) molecule has
      been studied in water solutions of various pH by potentiometry and electron
      paramagnetic resonance (EPR) and electron spin echo (ESE) spectroscopy.
      Potentiometric results indicate Cu(II) coordination by protonated NAD(+) at low
      pH and by deprotonated NAD(+) at high pH. At medium pH value (around pH=7) NAD(+)
      is not able to coordinate Cu(II) ions effectively and mainly the Cu(H(2)O)(6)
      complexes exist in the studied solution. This has been confirmed by EPR results.
      Electronic structure of Cu(II)-NAD complex and coordination sites is determined
      from EPR and ESE measurements in frozen solutions (at 77K and 6K). EPR spectra
      exclude coordination with nitrogen atoms. Detailed analysis of EPR parameters
      (g(||)=2.420, g(perpendicular)==2.080, A(||)=-131*10(-4)cm(-1) and
      A(perpendicular)=8*10(-4)cm(-1)) performed in terms of molecular orbital (MO)
      theory shows that Cu(II)NAD complex has elongated axial octahedral symmetry with
      a relatively strong delocalization of unpaired electron density on in-plane and
      axial ligands. The distortion of octahedron is analyzed using A(||) vs. g(||)
      diagram for various CuO(x) complexes. Electron spin echo decay modulation
      excludes the coordination by oxygen atoms of phosphate groups. We postulate a
      coordination of Cu(II) by two hydroxyl oxygen atoms of two ribose moieties of the
      NAD molecules and four solvated water molecules both at low and high pH values
      with larger elongation of the octahedron at higher pH.

PMID- 22484249
TI  - Butyltin(IV) 2-sulfobenzoates: synthesis, structural characterization and their
      cytostatic and antibacterial activities.
AB  - Three butyltin complexes with 2-sulfobenzoic acid
      [Sn(C(4)H(9))(2){O(3)SC(6)H(4)COO-2}(H(2)O)].(C(2)H(5)OH) (1),
      [Sn(C(4)H(9))(3){O(3)SC(6)H(4)COOH-2}] (2) and [Sn(2)(C(4)H(9))(6){MU
      O(3)SC(6)H(4)COO-2}] (3) have been synthesized and characterized by IR and (1)H,
      (13)C and (119)Sn NMR spectra. They show interesting properties in solid state
      and solutions because there are many modes of coordination of the Sbz ligand. The
      structure of complex 1 has been determined by X-ray crystallography. It is a
      chain compound with 2-sulfonatobenzoate coordinated to Sn atoms as a bridging and
      chelate ligand via O atoms of COO and SO(3) groups. In solutions the chains
      dissociate giving mainly mononuclear complexes. The NMR spectra and calculation
      at the DFT B3LYP/3-21G** level indicate that in solutions of compounds 1, 2 and 3
      in polar solvents, many complexes showing dynamic properties are formed. Density
      functional theory (DFT) calculations showed that many five- and six-coordinate
      isomers and conformers can exist in equilibrium. All compounds effectively
      interact with AMP and ATP. The NMR spectra showed that nucleotides are
      coordinated to Sn atoms via PO(4) groups. The complexes are very active
      cytostatic agents against tumor strains. They are more effective than cisplatin.
      It is interesting that activity of 3 against non-tumor cell NHDF is lower than
      against tumor cells. Antibacterial activity of 1 and 2 has been investigated.
      Compound 2 is a very effective agent against Gram-positive bacteria.
      Antibacterial activity of 1 is lower than that of 2. Activity of 1 both against
      Gram-positive and Gram-negative bacteria is similar.

PMID- 22484250
TI  - Preparation and validation of a skin model for the evaluation of intradermal
      powder injection devices.
AB  - A very promising novel needle-free application method is epidermal powder
      immunisation, a method delivering particulate vaccines into the viable epidermis
      of human skin where a dense network of immunocompetent cells resides. These
      antigen-presenting cells (Langerhans cells) are able to recognise antigens,
      process them and present them to naive T-cells and induce effective immune
      responses. Powder injection devices are being developed, and their evaluation is
      essential before applying them on live animals and individuals. An appropriate
      skin model will accelerate the development of such injection devices. Different
      films made from gelatin, silicon and agar were prepared and investigated as skin
      model candidates for the evaluation of powder injection devices. The mechanical
      properties of the skin model candidates were measured with an indentation method
      using a texture analyser, and the results were compared to the properties of
      human skin and pig skin. The indentation behaviour of the model films and the
      biological skin samples suggest that gelatin films plasticised with glycerol are
      very well suitable for a skin model. The mechanical properties of gelatin based
      films can be tailored by changing the glycerol content in the film making it even
      possible to simulate human skin with different mechanical properties as the
      mechanical properties depend on the individual, age, sex and site of injection.
      The stability of the gelatin films was also investigated under long-term storage.
      In addition, confocal laser scanning microscopy was used as a novel tool to
      determine the depths and size of fluorescently labelled particles in the gelatin
      model.

PMID- 22484251
TI  - On the effectiveness of noise masks: naturalistic vs. un-naturalistic image
      statistics.
AB  - It has been argued that the human visual system is optimized for identification
      of broadband objects embedded in stimuli possessing orientation averaged power
      spectra fall-offs that obey the 1/f(beta) relationship typically observed in
      natural scene imagery (i.e., beta=2.0 on logarithmic axes). Here, we were
      interested in whether individual spatial channels leading to recognition are
      functionally optimized for narrowband targets when masked by noise possessing
      naturalistic image statistics (beta=2.0). The current study therefore explores
      the impact of variable beta noise masks on the identification of narrowband
      target stimuli ranging in spatial complexity, while simultaneously controlling
      for physical or perceived differences between the masks. The results show that
      beta=2.0 noise masks produce the largest identification thresholds regardless of
      target complexity, and thus do not seem to yield functionally optimized channel
      processing. The differential masking effects are discussed in the context of
      contrast gain control.

PMID- 22484252
TI  - Histopathological stainings and definitions of vascular disruptions in the
      elderly brain.
AB  - Post-mortem neuropathological examination still remains an important tool not
      only to confirm the clinical diagnosis of the neurodegenerative dementia but also
      for research purposes. Cerebrovascular lesions are more and more suspected to be
      involved in the pathogenesis of Alzheimer dementia (AD). In particular the
      occurrence of small cerebral bleeds becomes a main topic of interest. Post-mortem
      brain examination, using standard quantification techniques, allows to determine
      its bleeding load. In AD amyloid angiopathy is not the only cause of small
      bleeds, while in other neurodegenerative dementias the bleeding load is low and
      mainly related to associated disturbances of the blood-brain barrier.

PMID- 22484254
TI  - Interaction between water-soluble rhodium complex RhCl(CO)(TPPTS)2 and
      surfactants probed by spectroscopic methods.
AB  - The interactions of rhodium complex RhCl(CO)(TPPTS)(2) [TPPTS=P(m
      C(6)H(4)SO(3)Na)(3)] with cationic, nonionic, and anionic surfactants have been
      investigated by UV-vis, fluorescence and (1)H NMR measurements. The presence of
      four different species of RhCl(CO)(TPPTS)(2) in cationic cetyltrimethylammonium
      (CTAB) solution has been demonstrated: free rhodium complex, rhodium complex
      bound to CTAB monomer, rhodium complex bound to CTAB premicelles, rhodium complex
      bound to CTAB micelles. The spectroscopy data show that RhCl(CO)(TPPTS)(2) can
      adsorb on the interface of cationic CTAB micelles by strong electrostatic
      attraction, weakly bind to the nonionic polyoxyethylene (20) sorbitan monolaurate
      (Tween 20) micelles by hydrophobic interaction, and does not interact with anion
      sodium dodecyl sulfate (SDS) micelles due to the strong electrostatic repulsion.

PMID- 22484255
TI  - Comparative investigation on the spectroscopic properties of Pr3+-doped boro
      phosphate, boro-germo-silicate and tellurite glasses.
AB  - We report on the spectroscopic properties of Pr(3+)-doped boro-phosphate, boro
      germo-silicate and tellurite glasses. The stimulated absorption and emission
      cross sections were estimated. Only one emission at 596 nm and 605 nm is observed
      in Pr(3+)-doped boro-phosphate and boro-germo-silicate glasses, respectively,
      while three emissions at 605 nm, 612 nm and 645 nm are observed in Pr(3+)-doped
      tellurite glass when excited at 467 nm. The fluorescence lifetime at 600 nm in
      Pr(3+)-doped boro-phosphate, boro-germo-silicate and tellurite glasses is 137
      MUs, 73 MUs and 51 MUs, respectively. The emissions from Pr(3+)-doped boro
      phosphate, boro-germo-silicate and tellurite glasses show different decay
      behaviors and can be well explained by multiphonon relaxation theory.

PMID- 22484253
TI  - Ca2+-activated adenylyl cyclase 1 introduces Ca2+-dependence to beta-adrenergic
      stimulation of HCN2 current.
AB  - Previous observations show that beta-adrenergic modulation of pacemaker current
      (I(f)) in sinoatrial node (SAN) cells is impaired by disruption of normal Ca(2+)
      homeostasis with ryanodine or BAPTA. Recently, the presence of Ca(2+)-activated
      adenylyl cyclase (AC) 1 was reported in SAN, and was proposed as a possible
      mechanism of Ca(2+)-dependence of beta-adrenergic modulation. However, direct
      evidence that pacemaker (HCN) channels can be regulated by Ca(2+)-activated AC
      and that such regulation introduces Ca(2+) dependence, is lacking. Here we co
      expressed AC1 or AC6 with HCN2 in neonatal rat ventricular myocytes, which lack
      AC1. Although both isoforms have equivalent expression level and ability to
      interact with HCN2, only AC1 increases intracellular cAMP content, accelerates
      spontaneous beating rate and modifies HCN2 biophysics. Measured HCN2 current in
      the AC1 group activated ~10mV more positive than in GFP or AC6. The beta
      adrenergic agonist isoproterenol induced a further positive shift under control
      conditions, but failed to do so after pretreatment with the Ca(2+) chelator
      BAPTA. In the AC6 group, isoproterenol shifted the HCN2 activation relation to a
      similar extent in the absence and presence of BAPTA. Thus, AC1 but not AC6 over
      expression introduces Ca(2+)-sensitivity to the beta-adrenergic response of HCN2.
      These results demonstrate physical and functional interaction between AC isoforms
      and the HCN2 pacemaker channel and support a key role of Ca(2+) activated AC1 as
      a molecular mechanism in Ca(2+)-dependent modulation of beta-adrenergic response
      of heart rate.

PMID- 22484256
TI  - Thermoluminescence and EPR studies of nanocrystalline Nd2O3:Ni2+ phosphor.
AB  - Nanocrystalline Nd(2)O(3):Ni(2+) (2 mol%) phosphor has been prepared by a low
      temperature (~400 degrees C) solution combustion method, in a very short time (<5
      min). Powder X-ray diffraction results confirm the single hexagonal phase of
      nanopowders. Scanning electron micrographs show that nanophosphor has porous
      nature and the particles are agglomerated. Transmission electron microscopy
      confirms the nanosize (20-25 nm) of the crystallites. The electron paramagnetic
      resonance (EPR) spectrum exhibits a symmetric absorption at g~2.77 which suggests
      that the site symmetry around Ni(2+) ions is predominantly octahedral. The number
      of spins participating in resonance (N) and the paramagnetic susceptibility (chi)
      has been evaluated. Raman study show major peaks, which are assigned to F(g) and
      combination of A(g)+E(g) modes. Thermoluminescence (TL) studies reveal well
      resolved glow peaks at 169 degrees C along with shoulder peak at around 236
      degrees C. The activation energy (E in eV), order of kinetics (b) and frequency
      factor (s) were estimated using glow peak shape method. It is observed that the
      glow peak intensity at 169 degrees C increases linearly with gamma-dose which
      suggest that Nd(2)O(3):Ni(2+) is suitable for radiation dosimetry applications.

PMID- 22484257
TI  - A theoretical study on cellular antioxidant activity of selected flavonoids.
AB  - The antioxidant capacities of the selected flavonoids quercetin, luteolin and
      taxifolin have been investigated at density functional level of theory with the
      aim of verifying the cellular antioxidant activity (CAA) values representative of
      experimental findings. The selected flavonoids were believed to act through the H
      atom transfer mechanism. Their potentiality of hydrogen abstraction was evaluated
      by computing the OH bond dissociation enthalpy (BDE) in gas-phase and in
      dimethylsulfoxide solution. Results indicate that the order of antioxidant
      efficacies calculated in this work is in agreement with that reported by
      experimental results of CAA. Time-dependent density functional theory (TDDFT)
      calculations were also performed both in gas-phase and in dimethylsulfoxide to
      reproduce the electronic UV-vis spectra of the selected flavonoids.

PMID- 22484258
TI  - Synthesis and physico-chemical studies of cyclometalated heteroleptic
      iridium(III) complexes.
AB  - Phosphorescent studies of 2-arylimidazole heteroleptic cyclometalated
      iridium(III) complexes with picolinic acid as the ancillary ligand were made. The
      observed experimental data reveals that these complexes possess dominantly
      (3)MLCT and (3)pi-pi* excited states and the solvent shift of these complexes are
      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(emi).

PMID- 22484259
TI  - A highly selective colorimetric sensor for Hg2+ based on nitrophenyl
      aminothiourea.
AB  - A simple and highly selective colorimetric sensor (L1) bearing thiosemicarbazide
      moiety as binding site and nitrophenyl moiety as signal group were synthesized.
      Sensor L1 showed great colorimetric single selectivity and high sensitivity for
      mercury cation in DMSO and DMSO/H(2)O binary solutions. When Hg(2+) was added to
      the DMSO solution of L1, dramatic color change from brown to colorless was
      observed. While the cations Ca(2+), Mg(2+), Cd(2+), Fe(3+), Co(2+), Ni(2+),
      Cu(2+), Zn(2+), Pb(2+), Ag(+) and Cr(3+) could not cause any distinct interferer
      toward the recognition process for Hg(2+). The detection limit is allowable to
      5.0 * 10(-6) and 1.0 * 10(-7)M level of Hg(2+) according to visual color change
      and UV-vis change, respectively. The recognition mechanism of the sensor toward
      mercury cation was evaluated in DMSO solutions by UV-vis and (1)H NMR. The sensor
      selectively sense Hg(2+)via the formation of a stable 1:1 complex through CS and
      CO group with Hg(2+). When these complex bonds formed, the sensor carried out an
      ICT transition induced color change.

PMID- 22484260
TI  - Developing biologically active compounds having efficient DNA binding and
      cleavage activity: spectroscopic investigation.
AB  - A new series of novel o-acetoacetotoluidide derived Schiff base and its metal
      complexes have been synthesized and structurally characterized. Elemental
      analysis, magnetic and spectroscopic data suggest that the complexes have
      octahedral geometry. Binding of these complexes with CT-DNA has been analyzed by
      absorption spectra, viscosity, cyclicvoltammetry and molecular docking analysis.
      Detailed analysis reveals that the metal complexes intercalate into the DNA base
      stack as intercalators. All the metal complexes cleave the pBR322 DNA upon
      irradiation. Antibacterial and antifungal activities of the ligand and its metal
      complexes are also explored and it has been observed that the complexes exhibit
      excellent activity against all types of bacteria and fungi than the ligand.

PMID- 22484261
TI  - FT-IR spectral studies on certain human urinary stones in the patients of rural
      area.
AB  - Fourier transform infrared spectroscopy (FT-IR) has been carried out to analyze
      the organic and inorganic constituent of human urinary stones. Patient's hailing
      from Rajah Muthiah Medical College and Hospital, Annamalai University, Tamil
      Nadu, India was selected for the study. The FT-IR results indicate that stones
      have different composition, i.e., namely calcium oxalate, calcium phosphate,
      carbonate apatite and magnesium ammonium phosphate and uric acid. From the
      spectral and powder X-ray diffraction pattern, the chemical constituents of
      urinary stones were identified. The quantitative estimations of calcium oxalate
      monohydrate (COM) 1,620 cm(-1), calcium phosphate (apatite) 1,037 cm(-1),
      magnesium ammonium phosphate (struvite) 1,010 cm(-1), calcium carbonate 1,460 cm(
      1) and uric acid 1,441 cm(-1) were calculated using particular peaks of FT-IR
      studies. The study reveals that calcium oxalate monohydrate and calcium phosphate
      type urinary stones were predominant whereas magnesium ammonium phosphate are in
      moderate level, and calcium carbonate and uric acid are in low. Calcium phosphate
      is found in all the stones and calcium oxalate monohydrate is found to be higher.
      Quantitative analyses of urinary stones show that calcium oxalate monohydrate
      (40%), apatite (30%), magnesium ammonium phosphate (23%) and uric acid (7%) are
      present in all the urinary stone samples.

PMID- 22484262
TI  - SERS and DFT investigation of 1-(2-pyridylazo)-2-naphthol and its metal complexes
      with Al(III), Mn(II), Fe(III), Cu(II), Zn(II) and Pb(II).
AB  - The development of surface-enhanced Raman scattering (SERS) as a prospective
      analytical methodology for detection of metal ions was shown in recent years by
      several studies on metal complexes. In this work, 1-(2-pyridylazo)-2-naphthol
      (PAN) and its Al(III), Mn(II), Fe(III), Cu(II), Zn(II) and Pb(II) complexes were
      studied by FTIR, FT-Raman and surface enhanced Raman spectroscopies. Molecular
      geometry optimization, molecular electrostatic potential (MEP) distribution and
      vibrational frequencies calculations were performed using the hybrid B3LYP
      exchange-correlation functional for the PAN molecule and its bidentate complexes.
      The calculated MEP distributions indicated the atoms with highest
      electronegativity, the adsorption to the silver surface occurring through these
      atoms. Based on experimental and theoretical data we were able to identify unique
      and representative features, useful for the identification of each PAN-metal
      complex.

PMID- 22484263
TI  - Absorption and photoconductivity spectra of Ag2GeS3 crystal: experiment and
      theory.
AB  - Spectral features of polycrystalline Ag(2)GeS(3) samples synthesized from high
      purity elements (at least 99.99 wt.% purity) in quartz ampoules evacuated to 0.1
      Pa were explored. The band energy gap of Ag(2)GeS(3) crystals estimated from the
      fundamental absorption edge and photoconductivity spectra were found to be equal
      to 1.98 eV and 2.16 eV, respectively. Simultaneously we have performed
      calculations of the band structure, total and partial density of states and the
      electron charge density using the ab initio FP-LAPW method. All the calculations
      were performed with four different exchange-correlation (xc) potentials. It was
      found that the effect of using different xc is very marginal on the valence band
      maximum (VBM) while it is dramatically shifted the conduction band minimum (CBM)
      towards higher energies with respect to the Fermi energy position. Our
      theoretical results have given a band energy gap equal to 0.40 eV (for LDA), 0.42
      eV (GGA), 1.03 eV (EVGGA) and 1.30 eV (mBJ) xc potentials. Thus the
      underestimation of the energy gap in LDA and GGA was partially corrected in EVGGA
      and mBJ model. As a remarkable fact mBJ did not bring the energy band gap very
      close to the experimental once. We have discovered that the Ag-s states have only
      a small effect on the conduction bands shifts whereas Ge-s states have a strong
      effect in extending of the gap, while remaining the valence bands unchanged.

PMID- 22484264
TI  - Structural, electrochemical characterization and SOD mimic activities of 1D chain
      or 3D network encouraged by unique MU2-bridging by adipate ion in mixed ligand
      complexes containing alpha-diimine as auxiliary ligand.
AB  - The present ternary complexes [Cu(ada)(phen)(H(2)O)].2H(2)O (1),
      [Co(2)(ada)(2)(phen)(2)(H(2)O)(2)] (2) and [{Cu(ada)(3)(bipy)}(n).3nH(2)O] (3)
      (H(2)ada=adipic acid, phen=1,10-phenanthroline and bipy=2,2'-bipyridine) obtained
      under varying experimental conditions were characterized by spectral,
      electrochemical and thermal studies. The bonding modes and the spatial
      arrangements of the carboxylate dianion around the metal ions have been
      investigated employing FTIR, EPR and X-ray crystallographic studies. Present data
      revealed a six coordinate distorted octahedral geometry for 2 with a=8.068,
      b=9.788, c=11.788A, alpha=70.464, beta=75.109, gamma=72.063 degrees  and a five
      coordinate square pyramidal geometry for 3 with a=9.509, b=9.912, c=12.656A,
      alpha=70.486, beta=73.604, gamma=75.162 degrees . The superoxide dismutase (SOD)
      mimic activities of the complexes are in the order 1>3>2.

PMID- 22484265
TI  - Structural and optical study of mixed structure of ZnO(hexagonal)/ZnS(cubic)
      nanocomposites.
AB  - ZnO, ZnS and ZnO/ZnS nanocomposites were successfully synthesized by chemical
      method in an air atmosphere. Water-ethanol matrix was used as solvent. The as
      obtained samples were characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM), UV-visible (UV-vis) and photoluminescence (PL)
      spectrophotometer. The results showed that the ZnS nanoparticles are cubic in
      structure with the size of about 5 nm growed on the surface of the hexagonal ZnO
      nanocomposites. The optical study of ZnO/ZnS nanocomposites showed an enhanced PL
      emission in visible region. The photoluminescence property of the ZnO/ZnS
      core/shell nanocomposites is varied with respect to the shell thicknesses. PL
      quenching is observed by increasing of shell thickness on ZnO.

PMID- 22484266
TI  - Spectral, thermal, structural, dielectric and microhardness studies of gel grown
      diaquasuccinatocadmium(II) hemihydrate.
AB  - Diaquasuccinatocadmium(II) hemihydrate (DSCH) single crystals were grown
      successfully by single gel diffusion technique at room temperature. Block shaped
      crystals of size 11 mm * 6 mm * 3 mm have been obtained in 24 days. The grown
      crystals were colorless and transparent. The crystalline nature and reflection
      planes of the sample were confirmed by the powder X-ray diffraction technique.
      The crystal structure of the DSCH crystal was determined by single crystal X-ray
      diffraction technique. According to microanalytical results the formula of the
      crystal is [Cd(C(4)H(4)O(4))H(2)O](2).0.5H(2)O. Fourier Transform Infrared (FT
      IR) and Fourier Transform Raman (FT-Raman) studies were used to confirm the
      presence of various functional groups in the crystal. The thermal behavior of the
      crystal was studied by simultaneous TGA-DTA methods in nitrogen atmosphere. The
      mechanical strength of the grown crystal was estimated by Vickers microhardness
      test. The dielectric behavior of the sample was also studied.

PMID- 22484267
TI  - Swift heavy ion induced structural, iono and photoluminescence properties of beta
      CaSiO3:Dy3+ nanophosphor.
AB  - CaSiO(3):Dy(3+) (1-5 mol%) nanophosphors have been prepared by a low temperature
      solution combustion method. The structural and luminescence (ionoluminescence; IL
      and photoluminescence; PL) studies have been carried out for pristine and ion
      irradiated samples. The XRD patterns of pristine sample show a prominent peak at
      (320) for the monoclinic structure of beta-CaSiO(3). Upon ion irradiation, the
      intensity of the prominent peak is decreased at the fluence of 7.81 * 10(12)ions
      cm(-2) and at higher fluence of 15.62 * 10(12)ions cm(-2), the prominent peak
      completely vanishes. The decrease in peak intensity might be due to the stress
      induced point defects. On-line IL and in situ PL studies have been carried out on
      pelletized samples bombarded with 100 MeV Si(7+) ions with fluences in the range
      (7.81-15.62)*10(12)ions cm(-2). The characteristic emission peaks at 481,574, 664
      and 754 nm recorded in both IL and PL are attributed to the luminescence centers
      activated by Dy(3+) ions. It is found that IL and PL emissions intensity
      decreases with increase in Si(7+) ion fluence. The decrease in intensity can be
      due to the destruction of Si-O-Si and O-Si-O type species present on the surface
      of the sample. FTIR studies also confirm the Si-O-Si and O-Si-O type species
      observed to be sensitive for swift heavy ion (SHI) irradiated samples.

PMID- 22484268
TI  - Spectral and hydrodynamic studies on p-toluidine induced growth in cationic
      micelle.
AB  - The effect of p-toluidine (PTD) on the growth of cationic surfactant micelles in
      aqueous solutions was examined by viscosity, UV-visible spectroscopy, dynamic
      light scattering (DLS), (1)H NMR and nuclear Overhauser effect spectroscopy
      (NOESY). Viscosity and scattering results are used to follow the growth of the
      aggregates and examine the structural transitions that occur. The reduction of
      electrostatic repulsions between the surfactant headgroups in combination with
      the hydrophobicity of the additive caused micellar growth and viscoelasticity at
      high PTD concentration; the micellar growth was found to be more pronounced in
      the presence of salt. (1)H NMR chemical shift changes reflect the interaction of
      PTD molecules with surfactant micelles while 2D NOESY experiments reveal that PTD
      molecules insert themselves in micelles such that its -CH(3) group is in contact
      with the core region and the benzene ring resides near the palisade layer of
      micelle.

PMID- 22484269
TI  - Photodynamic therapy potential of thiol-stabilized CdTe quantum dot-group 3A
      phthalocyanine conjugates (QD-Pc).
AB  - Thiol stabilized CdTe quantum dot (QD) nanoparticles were synthesized in aqueous
      phase and were used as energy donors to tetra-triethyleneoxythia substituted
      aluminum, gallium and indium phthalocyanines through fluorescence resonance
      energy transfer (FRET). Energy transfer occurred from the QDs to phthalocyanines
      upon photoexcitation of the QDs. An enhancement in efficiency of energy transfer
      with the nature of the carboxylic thiol stabilizer on the QDs was observed. As a
      result of the nanoparticle and the phthalocyanine mixing, the photoluminescence
      efficiency of the phthalocyanine moieties in the mixtures does not strictly
      follow the quantum yields of the bare phthalocyanines. The photochemistry study
      of phthalocyanines in the presence of the QDs revealed high singlet oxygen
      quantum yield, hence the possibility of using QDs in combination with
      phthalocyanines as photosensitizers in photodynamic therapy of cancer. The
      fluorescence of the CdTe quantum dots-phthalocyanine conjugates (QDs-Pc) were
      effectively quenched by addition of 1,4-benzoquinone.

PMID- 22484270
TI  - Interaction of tetramethylpyrazine with two serum albumins by a hybrid
      spectroscopic method.
AB  - The interactions of tetramethylpyrazine (TMPZ) with bovine serum albumin (BSA)
      and human serum albumin (HSA) have been investigated by various spectroscopic
      techniques. Fluorescence tests showed that TMPZ could bind to BSA/HSA to form
      complexes. The binding constants of TMPZ-BSA and TMPZ-HSA complexes were observed
      to be 1.442 * 10(4) and 3.302 * 10(4)M(-1) at 298K, respectively. The
      thermodynamic parameters (DeltaG, DeltaH and DeltaS) calculated on the basis of
      different temperatures revealed that the binding of TMPZ-HSA was mainly depended
      on hydrophobic interaction, and yet the binding of TMPZ-BSA might involve
      hydrophobic interaction strongly and electrostatic interaction. The results of
      synchronous fluorescence, three-dimensional fluorescence, UV-vis absorption, FT
      IR and CD spectra showed that the conformations of both BSA and HSA altered with
      the addition of TMPZ. The binding average distance between TMPZ and BSA/HSA was
      evaluated according to Foster non-radioactive energy transfer theory. In
      addition, with the aid of site markers (such as, phenylbutazone, ibuprofen and
      digitoxin), TMPZ primarily bound to tryptophan residues of BSA/HSA within site I
      (sub-domain II A).

PMID- 22484271
TI  - Encephalitis due to emerging viruses: CNS innate immunity and potential
      therapeutic targets.
AB  - The emerging viruses represent a group of pathogens that are intimately connected
      to a diverse range of animal vectors. The recent escalation of air travel climate
      change and urbanization has meant humans will have increased risk of contacting
      these pathogens resulting in serious CNS infections. Many RNA viruses enter the
      CNS by evading the BBB due to axonal transport from the periphery. The systemic
      adaptive and CNS innate immune systems express pattern recognition receptors PRR
      (TLRs, RiG-1 and MDA-5) that detect viral nucleic acids and initiate host
      antiviral response. However, several emerging viruses (West Nile Fever, Influenza
      A, Enterovirus 71 Ebola) are recognized and internalized by host cell receptors
      (TLR, MMR, DC-SIGN, CD162 and Scavenger receptor B) and escape immuno
      surveillance by the host systemic and innate immune systems. Many RNA viruses
      express viral proteins WNF (E protein), Influenza A (NS1), EV71 (protein 3C),
      Rabies (Glycoprotein), Ebola proteins (VP24 and VP 35) that inhibit the host cell
      anti-virus Interferon type I response promoting virus replication and
      encephalitis. The therapeutic use of RNA interference methodologies to silence
      gene expression of viral peptides and treat emerging virus infection of the CNS
      is discussed.

PMID- 22484272
TI  - Opportunistic infections in patients with pulmonary alveolar proteinosis.
AB  - OBJECTIVES: To describe the demographics, clinical manifestations, treatment, and
      outcomes of patients with pulmonary alveolar proteinosis (PAP) who developed an
      opportunistic infection with Nocardia spp., mycobacteria or fungal pathogens.
      METHODS: A case of PAP and Nocardia spp. brain abscess is described. A
      comprehensive review of the English-language literature was conducted to identify
      all reported cases of PAP and opportunistic infections between 1950 and July,
      2010. RESULTS: Seventy five cases were reviewed. Thirty two patients (43%) had
      nocardial infection, 28 (37%) mycobacterial infection, and 15 (20%) fungal
      infection. Thirty nine patients (65%) were male. Seventeen patients (23%) were
      immunosuppressed. Twenty patients (27%) were active smokers. PAP was the initial
      diagnosis in 19 patients (33%), while infection presented first in 23 patients
      (40%); 16 patients (27%) had a concurrent diagnosis of PAP and infection. The
      average interval between PAP diagnosis and an opportunistic infection was 16
      months. Lungs were the most common site of infection; extra-pulmonary infection
      was present in 27 patients (32%). Thirty nine patients (57%) survived through the
      follow-up period, while 31 died. CONCLUSIONS: Opportunistic infections can either
      precede or follow a diagnosis of PAP. PAP should be considered in apparently
      immunocompetent patients who present with an opportunistic infection and diffuse
      alveolar infiltrates.

PMID- 22484273
TI  - Coxsackievirus B5, associated with neurological hand, foot and mouth disease,
      China.

PMID- 22484274
TI  - Fusing proteins as an approach to study bioenergetic enzymes and processes.
AB  - Fusing proteins is an attractive genetic tool used in several biochemical and
      biophysical investigations. Within a group of redox proteins, certain fusion
      constructs appear to provide valuable templates for spectroscopy with which
      specific bioenergetic questions can be addressed. Here we briefly summarize three
      different cases of fusions reported for bacterial cytochrome bc(1) (prokaryotic
      equivalent of mitochondrial respiratory complex III), a common component of
      electron transport chains. These fusions were used to study supramolecular
      organization of enzymatic complexes in bioenergetic membrane, influence of the
      accessory subunits on the activity and stability of the complex, and molecular
      mechanism of operation of the enzyme in the context of its dimeric structure.
      Besides direct connotation to molecular bioenergetics, these fusions also
      appeared interesting from the protein design, biogenesis, and assembly points of
      view. This article is part of a Special Issue entitled: 17th European
      Bioenergetics Conference (EBEC 2012).

PMID- 22484275
TI  - Tracing the tail of ubiquinone in mitochondrial complex I.
AB  - Mitochondrial complex I (proton pumping NADH:ubiquinone oxidoreductase) is the
      largest and most complicated component of the respiratory electron transfer
      chain. Despite its central role in biological energy conversion the structure and
      function of this membrane integral multiprotein complex is still poorly
      understood. Recent insights into the structure of complex I by X-ray
      crystallography have shown that iron-sulfur cluster N2, the immediate electron
      donor for ubiquinone, resides about 30A above the membrane domain and mutagenesis
      studies suggested that the active site for the hydrophobic substrate is located
      next to this redox-center. To trace the path for the hydrophobic tail of
      ubiquinone when it enters the peripheral arm of complex I, we performed an
      extensive structure/function analysis of complex I from Yarrowia lipolytica
      monitoring the interaction of site-directed mutants with five ubiquinone
      derivatives carrying different tails. The catalytic activity of a subset of
      mutants was strictly dependent on the presence of intact isoprenoid moieties in
      the tail. Overall a consistent picture emerged suggesting that the tail of
      ubiquinone enters through a narrow path at the interface between the 49-kDa and
      PSST subunits. Most notably we identified a set of methionines that seems to form
      a hydrophobic gate to the active site reminiscent to the M-domains involved in
      the interaction with hydrophobic targeting sequences with the signal recognition
      particle of the endoplasmic reticulum. Interestingly, two of the amino acids
      critical for the interaction with the ubiquinone tail are different in bovine
      complex I and we could show that one of these exchanges is responsible for the
      lower sensitivity of Y. lipolytica complex I towards the inhibitor rotenone. This
      article is part of a Special Issue entitled: 17th European Bioenergetics
      Conference (EBEC 2012).

PMID- 22484276
TI  - Effects of cytokine and cytokine receptor gene variation on high anti-HB titers:
      following up on Taiwan's neonatal hepatitis B immunization program.
AB  - BACKGROUND: A significant percentage of Taiwanese neonatal HB immunization
      recipients have subsequently exhibited low anti-HB titers at non-protective or
      undetectable levels. Several mechanisms have been proposed to explain this
      phenomenon, including low vaccination responsiveness, deficient lymphocyte
      function, inappropriate antigen processing and presentation, and abnormal
      cytokine secretion. METHODS: To determine genetic influences resulting in high
      anti-HB titers, we divided a study cohort of 183 individuals into an anti
      HBs>=1000 mIU/mL group and a 10-1000 mIU/mL anti-HBs titer group. Chi-square
      tests were used to compare genotype and allelic frequencies between the two
      groups. RESULTS: Data from univariate and multivariate regression analyses of
      cytokine and cytokine receptor gene variants indicate (a) increased potential of
      high anti-HB titers in the presence of the TT genotype of the IL-4 rs2243250 SNP
      (OR=3.19; p=0.012) and the AA genotype of the IL-4R rs1805010 SNP (OR=2.25;
      p=0.048), and (b) individuals carrying the TT genotype of the IL-4 rs2243250 SNP
      had anti-HB titers at levels that were almost twice as high as those in
      individuals carrying the CC genotype (478.8 mIU/mL and 290.3 mIU/mL,
      respectively; p=0.033). CONCLUSION: Genetic determinants, especially IL-4 and IL
      4R, may contribute to high anti-HB titers in immune responses to HB vaccinations.

PMID- 22484277
TI  - Diminished toxicity of C-1748, 4-methyl-9-hydroxyethylamino-1-nitroacridine,
      compared with its demethyl analog, C-857, corresponds to its resistance to
      metabolism in HepG2 cells.
AB  - The narrow "therapeutic window" of anti-tumour therapy may be the result of drug
      metabolism leading to the activation or detoxification of antitumour agents. The
      aim of this work is to examine (i) whether the diminished toxicity of a potent
      antitumour drug, C-1748, 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine,
      compared with its 4-demethyl analogue, C-857, results from the differences
      between the metabolic pathways for the two compounds and (ii) the impact of
      reducing and/or hypoxic conditions on studied metabolism. We investigated the
      metabolites of C-1748 and C-857 formed in rat and human liver microsomes, with
      human P450 reductase (POR) and in HepG2 cells under normoxia and hypoxia. The
      elimination rate of C-1748 from POR knockout mice (HRN) was also evaluated. Three
      products, 1-amino-9-hydroxyethylaminoacridine, 1-aminoacridinone and a compound
      with an additional 6-membered ring, were identified for C-1748 and C-857 in all
      studied metabolic systems. The new metabolite was found in HepG2 cells. We showed
      that metabolic rate and the reactivity of metabolites of C-1748 were considerably
      lower than those of C-857, in all investigated metabolic models. Compared with
      metabolism under normoxia, cellular metabolism under hypoxia led to higher levels
      of 1-aminoacridine and aza-acridine derivatives of both compounds and of the 6
      membered ring metabolite of C-1748. In conclusion, the crucial role of hypoxic
      conditions and the direct involvement of POR in the metabolism of both compounds
      were demonstrated. Compared with C-857, the low reactivity of C-1748 and the
      stability of its metabolites are postulated to contribute significantly to the
      diminished toxicity of this compound observed in animals.

PMID- 22484278
TI  - Differential immune response in the hard clam (mercenaria mercenaria) against
      bacteria and the protistan pathogen QPX (quahog parasite unknown).
AB  - The immune response of the hard clam (quahog) Mercenaria mercenaria following
      challenge with live bacteria (Vibrio alginolyticus) and the protist QPX (Quahog
      Parasite Unknown) was investigated. The study also compared immune responses
      following QPX challenge in two different hard clam broodstocks exhibiting
      different degrees of susceptibility toward this parasite. Different immune and
      stress-related cellular and humoral factors were assessed including general
      hemocyte parameters (total and differential hemocyte counts, percentage of dead
      cells, reactive oxygen production, phagocytosis), parameters geared toward QPX
      (anti-QPX activity in plasma and hemocyte resistance to the cytotoxicity of QPX
      extracellular products). Two genes (ferritin and metallothionein) previously
      shown to be modulated following QPX exposure were molecularly characterized by
      rapid amplification of cDNA ends (RACE) and their transcription levels were
      determined in resistant and susceptible clams in response to QPX and bacterial
      challenge. Results indicated that both V. alginolyticus and QPX challenge
      triggered significant immune responses in clams with similar trends for most
      measured parameters. However, specific responses were observed for anti-QPX
      activity in plasma and hemocyte resistance to QPX products as well as ferritin
      and metallothionein expression according to each inoculum. Similarly, different
      response patterns were detected following QPX challenge in susceptible and
      resistant clam stocks. Resistant clams were able to elicit effective response
      against the parasite leading to the elimination of QPX and the restoration of
      constitutive immune status whereas QPX-susceptible clams triggered a strong
      immune modulation characterized by an acute phase response and associated acute
      phase protein but appeared to be less active in eliminating the parasite. These
      results suggest that different signaling pathways are triggered during V.
      alginolyticus and QPX challenge. Moreover, differences in the immune response
      toward QPX might be linked to the susceptibility or resistance of different clam
      stocks to the infection by this parasite.

PMID- 22484279
TI  - Identification of expressed genes in cDNA library of hemocytes from the RLO
      challenged oyster, Crassostrea ariakensis Gould with special functional
      implication of three complement-related fragments (CaC1q1, CaC1q2 and CaC3).
AB  - A SMARTerTM cDNA library of hemocyte from Rickettsia-like organism (RLO)
      challenged oyster, Crassostrea ariakensis Gould was constructed. Random clones
      (400) were selected and single-pass sequenced, resulted in 200 unique sequences
      containing 96 known genes and 104 unknown genes. The 96 known genes were
      categorized into 11 groups based on their biological process. Furthermore, we
      identified and characterized three complement-related fragments (CaC1q1, CaC1q2
      and CaC3). Tissue distribution analysis revealed that all of three fragments were
      ubiquitously expressed in all tissues studied including hemocyte, gills, mantle,
      digestive glands, gonads and adductor muscle, while the highest level was seen in
      the hemocyte. Temporal expression profile in the hemocyte monolayers reveled that
      the mRNA expression levels of three fragments presented huge increase after the
      RLO incubation at 3 h and 6 h in post-challenge, respectively. And the maximal
      expression levels at 3 h in post-challenge are about 256, 104 and 64 times higher
      than the values detected in the control of CaC1q1, CaC1q2 and CaC3, respectively.

PMID- 22484280
TI  - Acute gastroenteritis hospitalizations among children aged < 5 years before and
      after introduction of rotavirus vaccines: a hospital-based surveillance study in
      Galicia, Spain.
AB  - Rotavirus vaccines were licensed in Spain between late 2006 and early 2007.
      Rotavirus vaccination was recommended but not reimbursed by the Spanish National
      Health System. Significant coverage rates have been reached in Galicia, with an
      average of 47% since the period July 2007-June 2008. We aim to explore eventual
      variations in the incidence of hospitalizations for acute gastroenteritis (AGE)
      among children < 5 y of age before and after vaccine introduction. The annual and
      monthly hospitalization rates for rotavirus-related AGE and all cause AGE, before
      and after rotavirus vaccine introduction, were calculated by using the official
      surveillance system for hospital data. The annual hospitalization rates for
      rotavirus-related AGE in children < 5 y of age decreased by 14.8% for the period
      July 2008 to June 2009 and by 44.5% for the period July 2009 to June 2010 as
      compared with the median rate of the pre-vaccination period (July 2003 to June
      2007). The corresponding decreases for all cause AGE were 29.9% and 49.0%,
      respectively. In children < 12 mo of age a more marked decrease was observed.
      Compared with pre-vaccination years, a decrease in rotavirus-related and all
      cause AGE hospitalization rates was observed, with a greater decline in the July
      2009 to June 2010 period.

PMID- 22484281
TI  - Implications of water channel proteins in selected neurological disorders:
      epilepsies, muscular dystrophies, amyotrophic lateral sclerosis, neuromyelitis
      optica, Parkinson's disease, and spongiform encephalopathies.
AB  - The aim of this article is to describe the roles of water channel proteins (WCPs)
      in some neurological diseases in which the implications of these proteins became
      obvious in the decades after the discovery of WCPs of their presence in the CNS.
      The diseases which were selected for this review include: epilepsies, muscular
      dystrophies, amyotrophic lateral sclerosis, neuromyelitis optica, Parkinson's
      disease, and spongiform encephalopathies. The priorities of Benga group from Cluj
      Napoca, Romania, are mentioned, such as the idea of a generalized membrane defect
      affecting water permeability in epilepsy and in Duchenne muscular dystrophy. Some
      of these neurological disorders discussed in this article appeared to be water
      channelopathies. A typical example is neuromyelitis optica (NMO), in which the
      identification of the specific marker autoantibody against aquaporin 4 in the
      sera of patients was a milestone in the diagnosis. This has aided understanding
      of the pathogenesis of NMO and led to better control of its treatment. However,
      further studies are needed to characterize the function and regulation of WCPs in
      other neurological diseases, in particular to determine if modulation of WCP
      function may provide a novel approach to therapy in such diseases.

PMID- 22484282
TI  - A proposed model curriculum in global child health for pediatric residents.
AB  - OBJECTIVE: In response to the increasing engagement in global health (GH) among
      pediatric residents and faculty, academic GH training opportunities are growing
      rapidly in scale and number. However, consensus to guide residency programs
      regarding best practice guidelines or model curricula has not been established.
      We aimed to highlight critical components of well-established GH tracks and
      develop a model curriculum in GH for pediatric residency programs. METHODS: We
      identified 43 existing formal GH curricula offered by U.S. pediatric residency
      programs in April 2011 and selected 8 programs with GH tracks on the basis of our
      inclusion criteria. A working group composed of the directors of these GH tracks,
      medical educators, and trainees and faculty with GH experience collaborated to
      develop a consensus model curriculum, which included GH core topics, learning
      modalities, and approaches to evaluation within the framework of the competencies
      for residency education outlined by the Accreditation Council for Graduate
      Medical Education. RESULTS: Common curricular components among the identified GH
      tracks included didactics in various topics of global child health, domestic and
      international field experiences, completion of a scholarly project, and
      mentorship. The proposed model curriculum identifies strengths of established
      pediatric GH tracks and uses competency-based learning objectives. CONCLUSIONS:
      This proposed pediatric GH curriculum based on lessons learned by directors of
      established GH residency tracks will support residency programs in creating and
      sustaining successful programs in GH education. The curriculum can be adapted to
      fit the needs of various programs, depending on their resources and focus areas.
      Evaluation outcomes need to be standardized so that the impact of this curriculum
      can be effectively measured.

PMID- 22484283
TI  - Macrophage inhibitory cytokine-1 stimulates proliferation of human umbilical vein
      endothelial cells by up-regulating cyclins D1 and E through the PI3K/Akt-, ERK-,
      and JNK-dependent AP-1 and E2F activation signaling pathways.
AB  - Macrophage inhibitory cytokine-1 (MIC-1) is highly associated with malignant
      human cancers and has been suggested to be involved in tumor angiogenesis. In the
      present study, we examined the effect of MIC-1 on endothelial cell proliferation
      to confirm the angiogenesis-promoting role of MIC-1. MIC-1 treatment accelerated
      progression of the G(1) stage in the cell cycle of human umbilical vein
      endothelial cells (HUVECs), leading to an increased cell proliferation rate. MIC
      1 augmented the levels of cyclins D1 and E without altering the levels of cyclin
      dependent kinase (CDK) inhibitors, thereby increasing protein kinase activity of
      CDKs and subsequent phosphorylation of the Rb protein followed by nuclear
      translocation of E2F. MIC-1-induced expression of cyclins D1 and E was mediated
      by AP-1 and E2F-1 transcription factors, and among the AP-1 members, c-Jun and
      JunD appeared to participate in MIC-1-dependent transcription of the cyclin D1
      gene. Additionally, the PI3K/Akt, JNK, and ERK pathways were found to mediate MIC
      1-induced cyclin D1 expression in HUVECs. Importantly, lung endothelial cells
      isolated from MIC-1 transgenic mouse displayed a higher proliferation rate and
      cyclin D1 and E levels relative to their wild-type counterparts. These results
      suggest that MIC-1 secreted from cancer cells stimulates endothelial cell
      proliferation by enhancing AP-1- and E2F-dependent expression of G(1) cyclins via
      PI3K/Akt, JNK, and ERK signaling pathways, potentially leading to enhanced tumor
      angiogenesis.

PMID- 22484284
TI  - More accuracy to the EROD measurements--the resorufin fluorescence differs
      between species and individuals.
AB  - Ethoxyresorufin-O-deethylase (EROD) activity is a biomarker of exposure to planar
      aromatic hydrocarbons, and it is often measured from the S9 fraction. The effect
      of the liver S9 fraction of seven boreal freshwater fish species on the
      fluorescence of resorufin was studied. The S9 fractions diminished resorufin
      fluorescence by 40-80%, and there were large differences between species. Thus,
      using a resorufin standard curve without the S9 fraction leads to a large
      underestimation of the EROD activity. Therefore a microwell plate EROD method was
      developed that takes into account the effect of each sample on resorufin
      fluorescence. At least two mechanisms were involved in the decrease of the
      fluorescence: opaqueness of the sample, and enzymes (DT-diaphorase and plausibly
      NADPH-CYP450 oxidoreductase) that reduce resorufin to a non-fluorescent form.

PMID- 22484285
TI  - Lysine substitutions convert a bacterial-agglutinating peptide into a
      bactericidal peptide that retains anti-lipopolysaccharide activity and low
      hemolytic activity.
AB  - GL13NH2 is a bacteria-agglutinating peptide derived from the sequence of the
      salivary protein parotid secretory protein (PSP, BPIFA2, SPLUNC2, C20orf70). The
      peptide agglutinates both Gram negative and Gram positive bacteria, and shows
      anti-lipopolysaccharide activity in vitro and in vivo. However, GL13NH2 does not
      exhibit bactericidal activity. To generate a more cationic peptide with potential
      bactericidal activity, three amino acid residues were replaced with lysine
      residues to generate the peptide GL13K. In this report, the antibacterial and
      anti-inflammatory activities of GL13K were characterized. GL13K had lost the
      ability to agglutinate bacteria but gained bactericidal activity. Substitution of
      individual amino acids in GL13K with alanine did not restore bacterial
      agglutination. GL13K was bactericidal against Pseudomonas aeruginosa,
      Streptococcus gordonii and Escherichia coli but not Porphyromonas gingivalis.
      Unlike the agglutinating activity of GL13NH2, the bactericidal activity of GL13K
      against P. aeruginosa was retained in the presence of saliva. Both GL13NH2 and
      GL13K exhibited anti-lipopolysaccharide activity. In GL13K, this activity
      appeared to depend on a serine hydroxyl group. GL13K protected mice from
      lipopolysaccharide-induced sepsis and the peptide exhibited a low level of
      hemolysis, suggesting that it may be suitable for in vivo application.

PMID- 22484286
TI  - LVV-hemorphin 7 and angiotensin IV in correlation with antinociception and anti
      thermal hyperalgesia in rats.
AB  - Hemorphins, a family of atypical endogenous opioid peptides, are produced by the
      cleavage of hemoglobin beta-chain. Hemorphins were proved to bind to the MU
      opioid receptors (agonist) and angiotensin IV receptors (insulin-regulated
      aminopeptidase; IRAP) (inhibitor). Among the hemorphins, LVV-hemorphin-7 (LVV-H7)
      was found to be abundant and with a longer half life in the CNS. Using
      intrathecal and intracerebroventricular injections, LVV-H7 and angiotensin IV
      were given to the rats, which were then subjected to the plantar test and the
      tail-flick test. Our results showed that LVV-H7 attenuated carrageenan-induced
      hyperalgesia at the spinal level, which could not be reversed by the co
      administration of naloxone. At the supraspinal level, LVV-H7 also produced a
      significant anti-hyperalgesia effect but with a lower extent. Angiotensin IV
      showed a similar anti-hyperalgesia effect at the spinal level, but had no effect
      at the supraspinal level. In the tail-flick test and paw edema test, both
      peptides showed no effect. These results suggest that LVV-H7 mainly exert the
      anti-hyperalgesia effect at the spinal level, possibly through IRAP but not MU
      opioid receptors. In addition, we observed the expression of IRAP in the CNS of
      animals with/without carrageenan-induced hyperalgesia. Our results showed a
      significant expression of IRAP in the spinal cord of rats. However, there was no
      significant quantitative change of IRAP after the development of hyperalgesia.
      The serum level of LVV-H7 was also found to be with no change caused by
      hyperalgesia. These results indicated that the endogenous LVV-H7 and IRAP may not
      regulate the severity of hyperalgesia through a quantitative change.

PMID- 22484287
TI  - Differential changes in Substance P, VIP as well as neprilysin levels in patients
      with gastritis or ulcer.
AB  - The protective effect of capsaicin-sensitive sensory nerve (CSSN) activation was
      recently demonstrated in human gastric mucosa. We here examined changes in
      neuropeptides, specifically Substance P (SP), calcitonin-gene related peptide
      (CGRP) and vasoactive intestinal peptide (VIP) in patients with chronic gastritis
      or ulcer. Furthermore changes in neprilysin levels, which hydrolyse these
      neuropeptides, were determined. Gastric biopsies were obtained from both lesion-
      and normal-appearing mucosa of 57 patients. The presence of H. pylori infection
      was verified with rapid urease assay. Neuronal and non-neuronal levels of SP,
      VIP, CGRP and neprilysin activity were determined in freshly frozen biopsies.
      Immunohistochemical localization of neprilysin was performed in 30 paraffin
      embedded specimens. We here found that neuronal SP levels decreased significantly
      in normally appearing mucosa of patients with gastritis while levels of non
      neuronal SP increased in diseased areas of gastritis and ulcer. The presence of
      H. pylori led to further decreases of SP levels. The content of VIP in both
      disease-involved and uninvolved mucosa, and expression of neprilysin, markedly
      decreased in patients with gastritis or ulcer. Since VIP, as well as SP
      fragments, formed following hydrolysis with neprilysin is recognized to have
      gastroprotective effects, decreased levels of VIP, SP and neprilysin may
      predispose to cellular damage.

PMID- 22484288
TI  - Antimicrobial/cytolytic peptides from the venom of the North African scorpion,
      Androctonus amoreuxi: biochemical and functional characterization of natural
      peptides and a single site-substituted analog.
AB  - The venoms of scorpions are complex cocktails of polypeptide toxins that fall
      into two structural categories: those that contain cysteinyl residues with
      associated disulfide bridges and those that do not. As the majority of lethal
      toxins acting upon ion channels fall into the first category, most research has
      been focused there. Here we report the identification and structural
      characterization of two novel 18-mer antimicrobial peptides from the venom of the
      North African scorpion, Androctonus amoreuxi. Named AamAP1 and AamAP2, both
      peptides are C-terminally amidated and differ in primary structure at just two
      sites: Leu-->Pro at position 2 and Phe-->Ile at position 17. Synthetic replicates
      of both peptides exhibited a broad-spectrum of antimicrobial activity against a
      Gram-positive bacterium (Staphylococcus aureus), a Gram-negative bacterium
      (Escherichia coli) and a yeast (Candida albicans), at concentrations ranging
      between 20 MUM and 150 MUM. In this concentration range, both peptides produced
      significant degrees of hemolysis. A synthetic replicate of AamAP1 containing a
      single substitution (His-->Lys) at position 8, generated a peptide (AamAP-S1)
      with enhanced antimicrobial potency (3-5 MUM) against the three test organisms
      and within this concentration range, hemolytic effects were negligible. In
      addition, this His-->Lys variant exhibited potent growth inhibitory activity
      (ID(50) 25-40 MUm) against several human cancer cell lines and endothelial cells
      that was absent in both natural peptides. Natural bioactive peptide libraries,
      such as those that occur in scorpion venoms, thus constitute a unique source of
      novel lead compounds with drug development potential whose biological properties
      can be readily manipulated by simple synthetic chemical means.

PMID- 22484289
TI  - Neuropeptide B and W regulate leptin and resistin secretion, and stimulate
      lipolysis in isolated rat adipocytes.
AB  - Neuropeptide B (NPB) and W (NPW) regulate food intake and energy homeostasis in
      humans via two G-protein-coupled receptor subtypes, termed as GPR7 and GPR8.
      Rodents express GPR7 only. In animals, NPW decreases insulin and leptin levels,
      whereas the deletion of either NPB or GPR7 leads to obesity and hyperphagia.
      Metabolic and endocrine in vitro activities of NPW/NPB in adipocytes are unknown.
      We therefore characterize the effects of NPB and NPW on the secretion and
      expression of leptin and resistin, and on lipolysis, using rat adipocytes.
      Isolated rat adipocytes express GPR7 mRNA. NPB and NPW are expressed in
      macrophages and preadipocytes but are absent in mature adipocytes. Both, NPB and
      NPW reduce the secretion and expression of leptin from isolated rat adipocytes.
      NPB stimulates the secretion and expression of resistin, whereas both, NPB and
      NPW increase lipolysis. Our study demonstrates for the first time that NPB and
      NPW regulate the expression and secretion of leptin and resistin, and increase
      lipolysis in isolated rat adipocytes. These effects are presumably mediated via
      GPR7. The increase of resistin secretion, stimulation of lipolysis and the
      decrease of leptin secretion may represent mechanisms, through which NPB and NPW
      can affect glucose and lipid homeostasis, and food intake in rodents.

PMID- 22484290
TI  - A call for a policy change regarding publications based on transplantation of
      organs from executed prisoners.

PMID- 22484292
TI  - Novel CD8+ T cell-based vaccine stimulates Gp120-specific CTL responses leading
      to therapeutic and long-term immunity in transgenic HLA-A2 mice.
AB  - The limitations of highly active anti-retroviral therapy have necessitated the
      development of alternative therapeutics for human immunodeficiency virus type-1
      (HIV-1)-infected patients with dysfunctional dendritic cells (DCs) and CD4(+) T
      cell deficiency. We previously demonstrated that HIV-1 Gp120-specific T cell
      based Gp120-Texo vaccine by using ConA-stimulated C57BL/6 (B6) mouse CD8(+) T
      (ConA-T) cells with uptake of pcDNA(Gp120)-transfected B6 mouse DC line DC2.4
      (DC2.4(Gp120))-released exosomes (EXO(Gp120)) was capable of stimulating DC and
      CD4(+) T cell-independent CD8(+) cytotoxic T lymphocyte (CTL) responses detected
      in wild-type B6 mice using non-specific PE-anti-CD44 and anti-IFN-gamma antibody
      staining by flow cytometry. To assess effectiveness of Gp120-Texo vaccine in
      transgenic (Tg) HLA-A2 mice mimicking the human situation, we constructed
      adenoviral vector AdV(Gp120) expressing HIV-1 GP120 by recombinant DNA
      technology, and generated Gp120-Texo vaccine by using Tg HLA-A2 mouse CD8(+) ConA
      T cells with uptake of AdV(Gp120)-transfected HLA-A2 mouse bone marrow DC
      (DC(Gp120))-released EXO(Gp120). We then performed animal studies to assess Gp120
      Texo-induced stimulation of Gp120-specific CTL responses and antitumor immunity
      in Tg HLA-A2 mice. We demonstrate that Gp120-Texo vaccine stimulates Gp120
      specific CTL responses detected in Tg HLA-A2 mice using Gp120-specific PE-HLA
      A2/Gp120 peptide (KLTPLCVTL) tetramer staining by flow cytometry. These Gp120
      specific CTLs are capable of further differentiating into functional effectors
      with killing activity to Gp120 peptide-pulsed splenocytes in vivo. In addition,
      Gp120-Texo vaccine also induces Gp120-specific preventive, therapeutic (for 6 day
      tumor lung metastasis) and CD4(+) T cell-independent long-term immunity against
      B16 melanoma BL6-10(Gp120/A2Kb) expressing both Gp120 and A2Kb (alpha1 and alpha2
      domains of HLA-A2 and alpha3 domain of H-2K(b)) in Tg HLA-A2 mice. Taken
      together, the novel CD8(+) Gp120-Texo vaccine capable of stimulating efficient
      CD4(+) T cell-independent Gp120-specific CD8(+) CTL responses leading to
      therapeutic and long-term immunity in Tg HLA-A2 mice may represent a new
      immunotherapeutic vaccine for treatment of HIV-1 patients with CD4(+) T cell
      deficiency.

PMID- 22484291
TI  - High cumulative dose exposure to voriconazole is associated with cutaneous
      squamous cell carcinoma in lung transplant recipients.
AB  - BACKGROUND: Lung transplant recipients (LTR) have an increased risk of cutaneous
      squamous cell carcinoma (SCC) due to immunosuppressive therapy. Voriconazole,
      which is associated with phototoxic side effects in some patients, may be an
      additional risk factor for SCC in this population. METHODS: To test whether
      voriconazole is a risk factor for developing SCC in LTR, we evaluated cumulative
      exposure to voriconazole in 327 adults who underwent lung transplantation at one
      center between 1991 and 2010. Voriconazole exposure was assessed as a time
      varying covariate. We used survival analysis methods to assess the risk of
      developing SCC over time. RESULTS: Exposure to voriconazole was associated with a
      2.6-fold increased risk for SCC. This phenomenon was dose-dependent: the risk for
      SCC increased by 5.6% with each 60-day exposure at a standard dose of 200 mg
      twice daily. At 5 years after transplant, voriconazole conferred an absolute risk
      increase for SCC of 28%. CONCLUSIONS: These results suggest that caution should
      be taken when using voriconazole in LTR because this drug increases the already
      high risk for SCC in this population.

PMID- 22484293
TI  - Vaccine-critical videos on YouTube and their impact on medical students'
      attitudes about seasonal influenza immunization: a pre and post study.
AB  - YouTube is a video-sharing platform that is increasingly utilized to share and
      disseminate health-related information about immunization. Using a pre-post
      survey methodology, we compared the impact of two of the most popular YouTube
      videos discussing seasonal influenza vaccine, both vaccine-critical, on the
      attitudes towards immunizing of first year medical students attending a Canadian
      medical school. Forty-one medical students were randomized to view either a
      scientifically styled, seemingly "evidence-based", vaccine-critical video or a
      video using anecdotal stories of harms and highly sensationalized imagery. In the
      pre-intervention survey, medical students frequently used YouTube for all
      purposes, while 42% used YouTube for health-related purposes and 12% used YouTube
      to search for health information. While medical students were generally
      supportive of immunizing, there was suboptimal uptake of annual influenza vaccine
      reported, and a subset of our study population expressed vaccine-critical
      attitudes and behaviors with respect to seasonal influenza. Overall there was no
      significant difference in pre to post attitudes towards influenza immunization
      nor were there any differences when comparing the two different vaccine-critical
      videos. The results of our study are reassuring in that they suggest that medical
      students are relatively resistant to the predominately inaccurate, vaccine
      critical messaging on YouTube, even when the message is framed as scientific
      reasoning. Further empirical work is required to test the popular notion that
      information disseminated through social media platforms influences health-related
      attitudes and behaviors. However, our study suggests that there is an opportunity
      for public health to leverage YouTube to communicate accurate and credible
      information regarding influenza to medical students and others.

PMID- 22484294
TI  - Seroprevalence of measles among children affected by national measles elimination
      program in Korea, 2010.
AB  - BACKGROUND: Following the implementation of national measles elimination plan in
      Korea, the elimination was declared in 2006. In order to sustain the elimination,
      high population immunity should be continuously monitored. To evaluate the
      current age-related susceptibility within the Korean population, we conducted the
      seroprevalence in children and adolescents who were affected by the national
      measles elimination plan. METHODS: We used residual serum specimens to measure
      measles specific IgG and geometric mean titer (GMT) in birth cohorts 2007-2008
      and 1997-2003. Among birth cohorts, 2007-2008 cohorts were grouped to evaluate
      the timeliness of first dose of MMR, 1994-2003 cohorts were grouped to evaluate
      the effect of keep-up MMR2 campaign, and 1992-1993 cohorts were grouped to
      evaluate the effect of catch-up campaign in 2001. RESULTS: Overall, measles
      seropositivity rate was 86%. The highest seroprevalence of measles IgG was in
      birth cohorts 2007-2008. Measles seropositivity declined continuously in age
      groups. The birth cohorts 1994-1996 showed significantly lower levels of
      seropositivity and GMT than did the other birth cohorts. CONCLUSION: Despite
      efforts to eliminate measles for the past 10 years in Korea, our study revealed
      specific birth cohorts remaining at risk for transmission. The adolescents born
      during 1994-1996 had the lowest measles seropositivity levels, and might
      represent a 'pocket' that has potential at increased risk for measles
      transmission. Further discussion for follow-up immunization should be placed for
      consideration in the near future.

PMID- 22484295
TI  - Population-based surveillance for invasive pneumococcal disease and pneumonia in
      infants and young children in Bogota, Colombia.
AB  - BACKGROUND: In children <5 years of age, Streptococcus pneumoniae (SP) is,
      globally, the leading cause of vaccine-preventable death. Surveillance conducted
      in Bogota, Colombia estimated incidence rates of invasive pneumococcal disease
      (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); SP serotype
      distribution and antimicrobial susceptibility. METHODS: This prospective
      population-based surveillance was conducted from 2006 to 2008 in children 28 days
      to <36 months of age seeking care at SaludCoop centers. We determined incidence
      rates of IPD and pneumonia (clinical and CXR+Pn). Eligibility criteria included:
      temperature >=39.0 degrees C within 24h and/or clinical suspicion of IPD or
      pneumonia. Blood was obtained for culture in all children. Other sterile site
      specimens were obtained per routine practice. RESULTS: Of 8261 subjects enrolled,
      a total of 64 had invasive pneumococcal disease detected by isolation of SP from
      nonduplicative cultures (62) or detected solely by PCR and a clinical picture
      consistent with IPD (2). The overall IPD incidence rates for culture-positive
      only cases for children aged 28 days to <36 months was 76.4/100,000 per year for
      years 1 and 2 combined. Age stratification found the highest rates in children 6
      12 and 12 to <24 months of age. IPD incidence rates were assessed for bacteremic
      pneumonia (54.2/100,000), bacteremia (17.2/100,000), meningitis (3.7/100,000),
      and sepsis (1.2/100,000). Most common serotypes causing IPD were: 14 (51.6%), 6B
      (9.7%), and 19F (9.7%). Coverage of IPD cases by pneumococcal conjugate vaccine
      (PCV) 7, PCV10, and PCV13 was 77.4%, 85.5%, and 91.9%, respectively. Twenty-eight
      isolates (45.2%) were penicillin-nonsusceptible; PCV7 covered 96.3% of these;
      PCV10 covered 96.3% and PCV13 covered 100%. The overall incidence of clinical
      pneumonia and CXR+Pn was 6276/100,000 and 2120/100,000, respectively. CONCLUSION:
      Pneumococcal disease and pneumonia burden is considerable in children in Bogota,
      Colombia. Vaccination with pneumococcal conjugate vaccines has the potential to
      decrease this burden. Epidemiologic data are critical in assessing the potential
      impact of introduction of PCVs into national immunization schedules.

PMID- 22484296
TI  - Simple sequence repeat marker development from bacterial artificial chromosome
      end sequences and expressed sequence tags of flax (Linum usitatissimum L.).
AB  - Flax is an important oilseed crop in North America and is mostly grown as a fibre
      crop in Europe. As a self-pollinated diploid with a small estimated genome size
      of ~370 Mb, flax is well suited for fast progress in genomics. In the last few
      years, important genetic resources have been developed for this crop. Here, we
      describe the assessment and comparative analyses of 1,506 putative simple
      sequence repeats (SSRs) of which, 1,164 were derived from BAC-end sequences
      (BESs) and 342 from expressed sequence tags (ESTs). The SSRs were assessed on a
      panel of 16 flax accessions with 673 (58 %) and 145 (42 %) primer pairs being
      polymorphic in the BESs and ESTs, respectively. With 818 novel polymorphic SSR
      primer pairs reported in this study, the repertoire of available SSRs in flax has
      more than doubled from the combined total of 508 of all previous reports. Among
      nucleotide motifs, trinucleotides were the most abundant irrespective of the
      class, but dinucleotides were the most polymorphic. SSR length was also
      positively correlated with polymorphism. Two dinucleotide (AT/TA and AG/GA) and
      two trinucleotide (AAT/ATA/TAA and GAA/AGA/AAG) motifs and their iterations,
      different from those reported in many other crops, accounted for more than half
      of all the SSRs and were also more polymorphic (63.4 %) than the rest of the
      markers (42.7 %). This improved resource promises to be useful in genetic,
      quantitative trait loci (QTL) and association mapping as well as for anchoring
      the physical/genetic map with the whole genome shotgun reference sequence of
      flax.

PMID- 22484297
TI  - Donor preconditioning with rabbit anti-rat thymocyte immunoglobulin ameliorates
      ischemia reperfusion injury in rat kidney transplantation.
AB  - A major concern in transplantation is the preservation of organ function.
      Ischemia time and microcirculatory disturbance of the organ cannot be avoided and
      may result in ischemia reperfusion injury (IRI), increasing the risk of delayed
      graft function (DGF) and acute and chronic rejection. Anti-thymocyte
      immunoglobulin (rATG) is a polyclonal antibody preparation with multiple effects
      when administered to recipients. Our objective has been to evaluate whether the
      administration of rATG to kidney donors instead of recipients, in an experimental
      model of syngeneic rat transplantation, ameliorates IRI and facilitates immediate
      graft function recovery. Urea and creatinine levels and necrosis severity scores
      were significantly lower in kidneys from donors that had received rATG (urea:
      control: 211+/-8mg/dl vs. treatment: 110+/-15mg/dl, p<0.001; creatinine: control:
      4.6+/-0.24mg/dl vs. treatment: 2.6+/-0.22mg/dl, p<0.001; necrosis severity
      scores: control: 2.3 vs. treatment: 1.6, p<0.05). TUNEL staining showed 80+/-13
      positive cells in control group and 9+/-3 (p<0.001) in treatment group. In situ
      expression of proinflammatory cytokines TNF-alpha, IL-6, IL-21 and TGF-beta1 was
      reduced in rATG group (p<0.01); the same was observed for KIM-1 and caspase 8
      (p<0.001). Cytoprotective genes Bcl2 and HO-1 were upregulated in situ in
      treatment group (p<0.001). In situ expression of IL-17, caspase 9, IL-23a, CxCl3
      and ICAM1 showed no difference between groups (p>0.05). Findings suggest ATG
      administered to donors may ameliorate the IRI process in kidney transplantation,
      expressed by lower necrosis and apoptosis scores and the improvement of renal
      function, which may be explained through the diminished in situ expression of
      inflammatory mediators.

PMID- 22484298
TI  - Prospects of nanoparticle-DNA binding and its implications in medical
      biotechnology.
AB  - Bio-nanotechnology is a new interdisciplinary R&D area that integrates
      engineering and physical science with biology through the development of
      multifunctional devices and systems, focusing biology inspired processes or their
      applications, in particular in medical biotechnology. DNA based nanotechnology,
      in many ways, has been one of the most intensively studied fields in recent years
      that involves the use and the creation of bio-inspired materials and their
      technologies for highly selective biosensing, nanoarchitecture engineering and
      nanoelectronics. Increasing researches have been offered to a fundamental
      understanding how the interactions between the nanoparticles and DNA molecules
      could alter DNA molecular structure and its biochemical activities. This minor
      review describes the mechanisms of the nanoparticle-DNA binding and molecular
      interactions. We present recent discoveries and research progresses how the
      nanoparticle-DNA binding could vary DNA molecular structure, DNA detection, and
      gene therapy. We report a few case studies associated with the application of the
      nanoparticle-DNA binding devices in medical detection and biotechnology. The
      potential impacts of the nanoparticles via DNA binding on toxicity of the
      microorganisms are briefly discussed. The nanoparticle-DNA interactions and their
      impact on molecular and microbial functionalities have only drown attention in
      recent a few years. The information presented in this review can provide useful
      references for further studies on biomedical science and technology.

PMID- 22484299
TI  - Tissue engineering interventions for esophageal disorders--promises and
      challenges.
AB  - The diseases of the esophagus include congenital defects like atresia,
      tracheoesophageal fistula as well as others such as gastro-esophageal reflux
      disease (GERD), Barrett's esophagus, carcinoma and strictures. All esophageal
      disorders require surgical intervention and reconstruction with appropriate
      substitutes. Primary anastomosis is used to treat most cases but treatment of
      long gap atresia still remains a clinical challenge. Autologous graft therapies
      using tissues from colon, and small and large intestine or gastric
      transplantations have been attempted but have constraints like leakage, infection
      and stenosis at the implanted site, which leads to severe morbidity and
      mortality. An alternative for autologous grafts are allogenic and xenogenic
      grafts, which have better availability but disease transmission and
      immunogenicity limit their applications. Use of biodegradable and biocompatible
      scaffolds to engineer the esophagus promises to be an effective regenerative
      strategy for treatment of esophageal disorders. Nanotopography of the fibrous
      scaffolds mimics the natural extracellular matrix (ECM) of the tissue and
      incorporation of chemical cues and tailoring mechanical properties provide the
      right microenvironment for co-culture of different cell types. Scaffolds cultured
      with esophageal cells (epithelial cells, fibroblast and smooth muscle cells)
      might show enhancement of the biofunctionality in vivo. This review attempts to
      address the various strategies and challenges involved in successful tissue
      engineering of the esophagus.

PMID- 22484300
TI  - Marine biotechnology advances towards applications in new functional foods.
AB  - The marine ecosystem is still an untapped reservoir of biologically active
      compounds, which have considerable potential to supply food ingredients towards
      development of new functional foods. With the goal of increasing the availability
      and chemical diversity of functional marine ingredients, much research has been
      developed using biotechnological tools to discover and produce new compounds.
      This review summarizes the advances in biotechnological tools for production of
      functional ingredients, including enzymes, for the food industry. Tools involving
      biotechnological processes (bioreactors, fermentations, bioprocessing) and those
      involving genetic research designated as molecular biotechnology are discussed
      highlighting how they can be used in the controlled manipulation and utilization
      of marine organisms as sources of food ingredients, as well as discussing the
      most relevant shortcomings towards applications in new functional foods.

PMID- 22484301
TI  - Event-related potential (ERP) evidence for source-monitoring based on the absence
      of information.
AB  - Event-related potentials (ERPs) were recorded during a reality monitoring (RM)
      task (i.e., discriminating between seen and imagined words) and during an
      internal source monitoring (ISM) task (i.e., discriminating between self
      generated and imagined words). Behavioral measures indicated robust recollection
      during both tests with greater recollection during ISM. The ERP correlate of
      recollection, the parietal old/new effect, was observed for both seen and
      imagined words during RM but only for self-generated words during ISM. This
      evidence indicates that self-generated information was diagnostic of source and
      that recollection of imagined words was based on the absence of self-generated
      information during ISM. The late posterior negativity (LPN) ERP old/new effects
      were observed for all conditions; however, the generated word LPN was attenuated
      during ISM. This pattern is consistent with the hypothesis that it reflects
      continued evaluation of trace information and suggests that recovery of self
      generated information does not initiate an extensive evaluation of memory
      characteristics.

PMID- 22484302
TI  - Antiproliferative effect of oleuropein in prostate cell lines.
AB  - Currently, there is increasing interest in the in vivo protective effects of
      natural antioxidants found in dietary plants against oxidative damage caused by
      free radical species. Oxidative stress has been invoked as a causative agent in
      cancer and epidemiological data suggest that the consumption of fruits and
      vegetables may be associated with a lower incidence of cancer. The fruit of the
      Olea europaea L. and olive oil contain hundreds of phytochemicals and its
      extracts have recently been shown to exhibit antioxidant properties, due to the
      action of oleuropein. In view of these considerations, in this study, we
      investigated the effects of oleuropein on LNCaP and DU145 prostate cancer cell
      lines and on BPH-1 non-malignant cells. Oleuropein reduces cell viability and
      induces thiol group modifications, gamma-glutamylcysteine synthetase, reactive
      oxygen species, pAkt and heme oxygenase-1. Exposing cell cultures to oleuropein
      induces an antioxidant effect on BPH-1 cells and a pro-oxidant effect on cancer
      cells. Our results confirm the beneficial properties of olive oil and oleuropein,
      suggesting its possible use as an adjuvant agent in the treatment of prostatitis,
      in order to prevent the transformation of hypertrophic to cancerous cells.

PMID- 22484303
TI  - Hepatitis B virus X protein confers resistance of hepatoma cells to anoikis by up
      regulating and activating p21-activated kinase 1.
AB  - BACKGROUND & AIMS: Patients with chronic hepatitis B virus (HBV) infection are at
      risk for metastatic hepatocellular carcinoma (HCC). Metastatic cancer cells
      develop resistance to anoikis. The serine/threonine p21-activated kinase (PAK) 1
      regulates cytoskeletal dynamics and protects cells from anoikis; it also promotes
      virus replication. We investigated the effects of PAK1 on anoikis resistance in
      human hepatoma cells and in mice. METHODS: We transfected human hepatoma cells
      with pHBV1.3 (to mimic HBV replication) or plasmids encoding different HBV
      proteins; we performed colony formation and anoikis assays. We knocked down
      levels of PAK1 and Bcl2, or inhibited their activity, in hepatoma cells and
      quantified anoikis and growth of tumor xenografts in nude mice; we also measured
      anoikis of tumor cells isolated from ascites of the mice. We performed
      immunohistochemical analysis of PAK1 levels in HCC samples from patients.
      RESULTS: Human hepatoma cells transfected with pHBV1.3 expressing hepatitis B
      virus X protein (HBx) underwent anchorage-independent proliferation, were
      resistant to anoikis, and had higher levels of Bcl2 than nontransfected cells.
      Expression of HBx increased mitochondrial levels of Bcl2 and PAK1, which
      interacted physically. Anoikis resistance of Huh7 and SK-Hep1 cells required PAK1
      activity and Bcl2. Expression of HBx promoted growth of Huh7 xenograft tumors in
      mice; PAK1 knockdown reduced growth of these tumors in mice and anoikis of cells
      isolated from these tumors. In human HCC samples, increased levels of PAK1
      correlated with poor prognosis, HBV infection, and portal vein tumor thrombosis.
      CONCLUSIONS: The HBV protein HBx up-regulates PAK1, allows hepatoma cells to
      become resistant to anoikis, and promotes growth of aggressive xenograft tumors
      in mice. HBx induction of PAK1 might promote progression of HCC in patients with
      chronic HBV infection.

PMID- 22484304
TI  - Cognitive impairment and dementia in Parkinson's disease.
AB  - Relatively subtle cognitive disturbances may be present from the initial stages
      of Parkinson's disease (PD) that progress in many patients to a more severe
      cognitive impairment and dementia. Several of the initial deficits are ascribed
      to failure in the frontal-striatal basal ganglia circuits and involve executive
      defects in planning, initiation, monitoring of goal-directed behaviors and
      working-memory. Other non-demented PD patients also exhibit visuospatial and
      memory deficits more representative of posterior cortical functioning and fail
      performing naming or copying tasks. Major differences in the overall rate of
      cognitive decline among PD patients support the co-existence of at least two
      patterns of involution, differentiating a relatively slow decline of fronto
      striatal deficits from a more rapid decline of posterior-cortical deficits, with
      different pathophysiological substrates, genetics, prognosis and response to
      drugs used to treat the motor symptoms of PD.

PMID- 22484305
TI  - Distinct neural correlates of associative working memory and long-term memory
      encoding in the medial temporal lobe.
AB  - Increasing evidence suggests a role for the hippocampus not only in long-term
      memory (LTM) but also in relational working memory (WM) processes, challenging
      the view of the hippocampus as being solely involved in episodic LTM. However,
      hippocampal involvement reported in some neuroimaging studies using "classical"
      WM tasks may at least partly reflect incidental LTM encoding. To disentangle WM
      processing and LTM formation we administered a delayed-match-to-sample
      associative WM task in an event-related fMRI study design. Each trial of the WM
      task consisted of four pairs of faces and houses, which had to be maintained
      during a delay of 10 s. This was followed by a probe phase consisting of three
      consecutively presented pairs; for each pair participants were to indicate
      whether it matched one of the pairs of the encoding phase. After scanning, an
      unexpected recognition-memory (LTM) task was administered. Brain activity during
      encoding was analyzed based on WM and LTM performance. Hence, encoding-related
      activity predicting WM success in the absence of successful LTM formation could
      be isolated. Furthermore, regions critical for successful LTM formation for pairs
      previously correctly processed in WM were analyzed. Results showed that the left
      parahippocampal gyrus including the fusiform gyrus predicted subsequent accuracy
      on WM decisions. The right anterior hippocampus and left inferior frontal gyrus,
      in contrast, predicted successful LTM for pairs that were previously correctly
      classified in the WM task. Our results suggest that brain regions associated with
      higher-level visuo-perceptual processing are involved in successful associative
      WM encoding, whereas the anterior hippocampus and left inferior frontal gyrus are
      involved in successful LTM formation during incidental encoding.

PMID- 22484306
TI  - Measuring functional connectivity in MEG: a multivariate approach insensitive to
      linear source leakage.
AB  - A number of recent studies have begun to show the promise of
      magnetoencephalography (MEG) as a means to non-invasively measure functional
      connectivity within distributed networks in the human brain. However, a number of
      problems with the methodology still remain--the biggest of these being how to
      deal with the non-independence of voxels in source space, often termed signal
      leakage. In this paper we demonstrate a method by which non-zero lag cortico
      cortical interactions between the power envelopes of neural oscillatory processes
      can be reliably identified within a multivariate statistical framework. The
      method is spatially unbiased, moderately conservative in false positive rate and
      removes linear signal leakage between seed and target voxels. We demonstrate this
      methodology in simulation and in real MEG data. The multivariate method offers a
      powerful means to capture the high dimensionality and rich information content of
      MEG signals in a single imaging statistic. Given a significant interaction
      between two areas, we go on to show how classical statistical tests can be used
      to quantify the importance of the data features driving the interaction.

PMID- 22484307
TI  - Linking white matter integrity loss to associated cortical regions using
      structural connectivity information in Alzheimer's disease and fronto-temporal
      dementia: the Loss in Connectivity (LoCo) score.
AB  - It is well known that gray matter changes occur in neurodegenerative diseases
      like Alzheimer's (AD) and fronto-temporal dementia (FTD), and several studies
      have investigated their respective patterns of atrophy progression. Recent work,
      however, has revealed that diffusion MRI that is able to detect white matter
      integrity changes may be an earlier or more sensitive biomarker in both diseases.
      However, studies that examine white matter changes only are limited in that they
      do not provide the functional specificity of GM region-based analysis. In this
      study, we develop a new metric called the Loss in Connectivity (LoCo) score that
      gives the amount of structural network disruption incurred by a gray matter
      region for a particular pattern of white matter integrity loss. Leveraging the
      relative strengths of WM and GM markers, this metric links areas of WM integrity
      loss to their connected GM regions as a first step in understanding their
      functional implications. The LoCo score is calculated for three groups: 18AD, 18
      FTD, and 19 age-matched normal controls. We show significant correlations of the
      LoCo with the respective atrophy patterns in AD (R=0.51, p=2.2 * 10(-9)) and FTD
      (R=0.49, p=2.5 * 10(-8)) for a standard 116 region gray matter atlas. In
      addition, we demonstrate that the LoCo outperforms a measure of gray matter
      atrophy when classifying individuals into AD, FTD, and normal groups.

PMID- 22484308
TI  - Being right is its own reward: load and performance related ventral striatum
      activation to correct responses during a working memory task in youth.
AB  - The ventral striatum (VS) is a critical brain region for reinforcement learning
      and motivation. Intrinsically motivated subjects performing challenging cognitive
      tasks engage reinforcement circuitry including VS even in the absence of external
      feedback or incentives. However, little is known about how such VS responses
      develop with age, relate to task performance, and are influenced by task
      difficulty. Here we used fMRI to examine VS activation to correct and incorrect
      responses during a standard n-back working memory task in a large sample (n=304)
      of healthy children, adolescents and young adults aged 8-22. We found that
      bilateral VS activates more strongly to correct than incorrect responses, and
      that the VS response scales with the difficulty of the working memory task.
      Furthermore, VS response was correlated with discrimination performance during
      the task, and the magnitude of VS response peaked in mid-adolescence. These
      findings provide evidence for scalable intrinsic reinforcement signals during
      standard cognitive tasks, and suggest a novel link between motivation and
      cognition during adolescent development.

PMID- 22484309
TI  - Temperament trait Harm Avoidance associates with MU-opioid receptor availability
      in frontal cortex: a PET study using [(11)C]carfentanil.
AB  - Harm Avoidance is a temperament trait that associates with sensitivity to
      aversive and non-rewarding stimuli, higher anticipated threat and negative
      emotions during stress as well as a higher risk for affective disorders. The
      neurobiological correlates of interindividual differences in Harm Avoidance are
      largely unknown. We hypothesized that variability in Harm Avoidance trait would
      be explained by differences in the activity of MU-opioid system as the opioid
      system is known to regulate affective states and stress sensitivity. Brain MU
      opioid receptor availability was measured in 22 healthy subjects using positron
      emission tomography and [(11)C]carfentanil, a selective MU-opioid receptor
      agonist. The subjects were selected from a large Finish population-based cohort
      (N=2075) on the basis of their pre-existing Temperament and Character Scores.
      Subjects scoring consistently in the upper (10) and lower (12) quartiles for the
      Harm Avoidance trait were studied. High Harm Avoidance score associated with high
      MU-opioid receptor availability (i.e. lower endogenous MU-opioid drive) in
      anterior cingulate cortex, ventromedial and dorsolateral prefrontal cortices and
      anterior insular cortex. These associations were driven by two subscales of Harm
      Avoidance; Shyness with Strangers and Fatigability and Asthenia. In conclusion,
      higher Harm Avoidance score in healthy subjects is associated with higher MU
      opioid availability in regions involved in the regulation of anxiety as well as
      in the control of emotions, affective component of pain and interoceptive
      awareness. The results have relevance in the research of vulnerability factors
      for affective disorders.

PMID- 22484310
TI  - Learning piano melodies in visuo-motor or audio-motor training conditions and the
      neural correlates of their cross-modal transfer.
AB  - To investigate the cross-modal transfer of movement patterns necessary to perform
      melodies on the piano, 22 non-musicians learned to play short sequences on a
      piano keyboard by (1) merely listening and replaying (vision of own fingers
      occluded) or (2) merely observing silent finger movements and replaying (on a
      silent keyboard). After training, participants recognized with above chance
      accuracy (1) audio-motor learned sequences upon visual presentation (89+/-17%),
      and (2) visuo-motor learned sequences upon auditory presentation (77+/-22%). The
      recognition rates for visual presentation significantly exceeded those for
      auditory presentation (p<.05). fMRI revealed that observing finger movements
      corresponding to audio-motor trained melodies is associated with stronger
      activation in the left rolandic operculum than observing untrained sequences.
      This region was also involved in silent execution of sequences, suggesting that a
      link to motor representations may play a role in cross-modal transfer from audio
      motor training condition to visual recognition. No significant differences in
      brain activity were found during listening to visuo-motor trained compared to
      untrained melodies. Cross-modal transfer was stronger from the audio-motor
      training condition to visual recognition and this is discussed in relation to the
      fact that non-musicians are familiar with how their finger movements look (motor
      to-vision transformation), but not with how they sound on a piano (motor-to-sound
      transformation).

PMID- 22484311
TI  - 5-Hydroxy-7-methoxyflavone inhibits N-formyl-L-methionyl-L-leucyl-L-phenylalanine
      induced superoxide anion production by specific modulate membrane localization of
      Tec with a PI3K independent mechanism in human neutrophils.
AB  - Respiratory burst mediates crucial bactericidal mechanism in neutrophils.
      However, undesirable respiratory burst leads to pathological inflammation and
      tissue damage. This study investigates the effect and the underlying mechanism of
      5-hydroxy-7-methoxyflavone (MCL-1), a lignan extracted from the leaves of
      Muntingia calabura L. (Tiliaceae), on N-formyl-L-methionyl-L-leucyl-L
      phenylalanine (fMLP)-induced respiratory burst and cathepsin G release in human
      neutrophils. Signaling pathways regulated by MCL-1 to oppose fMLP-induced
      respiratory burst were evaluated by membrane localization of Tec induced by fMLP
      and by immunoblotting analysis of downstream phosphorylation targets of Tec.
      Briefly, MCL-1 specific inhibited fMLP-induced superoxide anion production in a
      concentration-dependent (IC(50)=0.16+/-0.01 MUM) and Tec kinase-dependent manner,
      however, MCL-1 did not affect fMLP-induced cathepsin G release. Further, MCL-1
      suppressed fMLP-induced Tec translocation from the cytosol to the inner leaflet
      of the plasma membrane, and subsequently activation of phospholipase Cgamma2
      (PLCgamma2). Moreover, MCL-1 attenuated PLCgamma2 activity and intracellular
      calcium concentration notably through extracellular calcium influx. Consequently,
      fMLP-induced phosphorylation of protein kinase C (PKC) and membrane localization
      of p47(phox) were decreased by MCL-1 in a Tec-dependent manner, while the
      phosphorylation of extracellular signal-regulated kinase (ERK), p38, AKT and Src
      tyrosine kinase family remained unaffected. In addition, MCL-1 neither inhibited
      NADPH oxidase activity nor increased cyclicAMP levels. MCL-1 specific opposes
      fMLP-mediated respiratory burst by inhibition of membrane localization of Tec and
      subsequently interfered with the activation of PLCgamma2, protein kinase C, and
      p47(phox).

PMID- 22484312
TI  - Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin
      induced diabetic rats.
AB  - Diabetic retinopathy is a complex disease that has potential involvement of
      inflammatory and oxidative stress-related pathways in its pathogenesis. We
      hypothesized that eriodictyol, one of the most abundant dietary flavonoids, could
      be effective against diabetic retinopathy, which involves significant oxidative
      stress and inflammation. The aim of the present study was to investigate the
      effects of eriodictyol in early retinal and plasma changes of streptozotocin
      induced diabetic rats. The effect of eriodictyol treatment (0.1, 1, 10 mg/kg
      daily for 10 days) was evaluated by TNF-alpha, ICAM-1, VEGF, and eNOS protein
      levels measurement in the retina, plasma lipid peroxidation, and blood-retinal
      barrier (BRB) integrity. Increased amounts of cytokines, adhesion molecule, and
      nitric oxide synthase were observed in retina from diabetic rats. Eriodictyol
      treatment significantly lowered retinal TNF-alpha, ICAM-1, VEGF, and eNOS in a
      dose-dependent manner. Further, treatment with eriodictyol significantly
      suppressed diabetes-related lipid peroxidation, as well as the BRB breakdown.
      These data demonstrated that eriodictyol attenuates the degree of retinal
      inflammation and plasma lipid peroxidation preserving the BRB in early diabetic
      rats.

PMID- 22484313
TI  - Estradiol induces cytochrome P450 2B6 expression at high concentrations:
      implication in estrogen-mediated gene regulation in pregnancy.
AB  - Pregnancy alters the rate and extent of drug metabolism, but little is known
      about the underlying molecular mechanism. We have found that 17beta-estradiol
      (E2) upregulates expression of the major drug-metabolizing enzyme CYP2B6 in
      primary human hepatocytes. Results from promoter reporter assays in HepG2 cells
      revealed that E2 activates constitutive androstane receptor (CAR) and enhances
      promoter activity of CYP2B6, for which high concentrations of E2 reached during
      pregnancy were required. E2 triggered nuclear translocation of CAR in primary rat
      hepatocytes that were transiently transfected with human CAR as well as in
      primary human hepatocytes, further confirming transactivation of CAR by E2. E2
      activated estrogen receptor (ER) also enhanced CYP2B6 promoter activity. The DNA
      binding domain of ER was not required for the induction of CYP2B6 promoter
      activity by E2, suggesting involvement of a non-classical mechanism of ER action.
      Results from deletion and mutation assays as well as electrophorectic mobility
      shift and supershift assays revealed that two AP-1 binding sites (-1782/-1776 and
      -1664/-1658 of CYP2B6) are critical for ER-mediated activation of the CYP2B6
      promoter by E2. Concurrent activation of both ER and CAR by E2 enhanced CYP2B6
      expression in a synergistic manner. Our data demonstrate that at high
      concentrations reached during pregnancy, E2 activates both CAR and ER that
      synergistically induce CYP2B6 expression. These results illustrate
      pharmacological activity of E2 that would likely become prominent during
      pregnancy.

PMID- 22484314
TI  - Vascular endothelin receptor type B: structure, function and dysregulation in
      vascular disease.
AB  - Endothelin-1 (ET-1) is a major regulator of vascular function, acting via both
      endothelin receptor type A (ET(A)R) and type B (ET(B)R). Although the role of
      ET(A)R in vascular smooth muscle (VSM) contraction has been studied, little is
      known about ET(B)R. ET(B)R is a G-protein coupled receptor with a molecular mass
      of ~50 kDa and 442 amino acids arranged in seven transmembrane domains.
      Alternative splice variants of ET(B)R and heterodimerization and cross-talk with
      ET(A)R may affect the receptor function. ET(B)R has been identified in numerous
      blood vessels with substantial effects in the systemic, renal, pulmonary,
      coronary and cerebral circulation. ET(B)R in the endothelium mediates the release
      of relaxing factors such as nitric oxide, prostacyclin and endothelium-derived
      hyperpolarizing factor, and could also play a role in ET-1 clearance. ET(B)R in
      VSM mediates increases in [Ca(2+)](i), protein kinase C, mitogen-activated
      protein kinase and other pathways of VSM contraction and cell growth. ET-1/ET(A)R
      signaling has been associated with salt-sensitive hypertension (HTN) and
      pulmonary arterial hypertension (PAH), and ET(A)R antagonists have shown some
      benefits in these conditions. In search for other pathogenetic factors and more
      effective approaches, the role of alterations in endothelial ET(B)R and VSM
      ET(B)R in vascular dysfunction, and the potential benefits of modulators of
      ET(B)R in treatment of HTN and PAH are being examined. Combined ET(A)R/ET(B)R
      antagonists could be more efficacious in the management of conditions involving
      upregulation of ET(A)R and ET(B)R in VSM. Combined ET(A)R antagonist with ET(B)R
      agonist may need to be evaluated in conditions associated with decreased
      endothelial ET(B)R expression/activity.

PMID- 22484315
TI  - Intestinal CYP3A4 and midazolam disposition in vivo associate with VDR
      polymorphisms and show seasonal variation.
AB  - Vitamin D, whose levels vary seasonally with sunlight, is activated to 1alpha,25
      dihydroxyvitamin D(3) that binds the vitamin D receptor (VDR) and
      transcriptionally regulates intestinal CYP3A4 expression. We genotyped VDR
      polymorphisms and determined their associations with intestinal CYP3A4 and with
      midazolam pharmacokinetics, and whether intestinal CYP3A4 levels/activity varied
      seasonally. The VDR BsmIG > A (rs1544410) polymorphism was significantly
      associated with CYP3A4 jejunal expression/activity, with CYP3A4 duodenal mRNA,
      and with midazolam area under the curve (AUC). Intestinal CYP3A4
      expression/activity was significantly higher in biopsies with the VDR promoter
      polymorphisms Cdx2-3731G > A and GATA-1012A > G that increase VDR activation of
      target genes. Duodenal CYP3A4 mRNA was significantly higher between April and
      September than between October and March. Midazolam p.o. AUC and oral
      bioavailability trended higher October through March compared to April through
      September. These data suggest VDR polymorphisms are predictors of intestinal
      CYP3A4, and that CYP3A4 intestinal expression varies seasonally--likely related
      to annual changes in UV sunlight and vitamin D levels.

PMID- 22484316
TI  - Synergistic substrate binding determines the stoichiometry of transport of a
      prokaryotic H(+)/Cl(-) exchanger.
AB  - Active exchangers dissipate the gradient of one substrate to accumulate
      nutrients, export xenobiotics and maintain cellular homeostasis. Mechanistic
      studies have suggested that two fundamental properties are shared by all
      exchangers: substrate binding is antagonistic, and coupling is maintained by
      preventing shuttling of the empty transporter. The CLC H(+)/Cl(-) exchangers
      control the homeostasis of cellular compartments in most living organisms, but
      their transport mechanism remains unclear. We show that substrate binding to CLC
      ec1 is synergistic rather than antagonistic: chloride binding induces protonation
      of a crucial glutamate. The simultaneous binding of H(+) and Cl(-) gives rise to
      a fully loaded state that is incompatible with conventional transport mechanisms.
      Mutations in the Cl(-) transport pathway identically alter the stoichiometries of
      H(+)/Cl(-) exchange and binding. We propose that the thermodynamics of
      synergistic substrate binding, rather than the kinetics of conformational changes
      and ion binding, determine the stoichiometry of transport.

PMID- 22484317
TI  - Human prion protein binds Argonaute and promotes accumulation of microRNA
      effector complexes.
AB  - Despite intense research in the context of neurodegenerative diseases associated
      with its misfolding, the endogenous human prion protein PrP(C) (or PRNP) has
      poorly understood physiological functions. Whereas most PrP(C) is exposed to the
      extracellular environment, conserved domains result in transmembrane forms of
      PrP(C) that traffic in the endolysosomal system and are linked to inherited and
      infectious neuropathologies. One transmembrane PrP(C) variant orients the N
      terminal 'octarepeat' domain into the cytoplasm. Here we demonstrate that the
      octarepeat domain of human PrP(C) contains GW/WG motifs that bind Argonaute (AGO)
      proteins, the essential components of microRNA (miRNA)-induced silencing
      complexes (miRISCs). Transmembrane PrP(C) preferentially binds AGO, and PrP(C)
      promotes formation or stability of miRISC effector complexes containing the
      trinucleotide repeat-containing gene 6 proteins (TNRC6) and miRNA-repressed mRNA.
      Accordingly, effective repression of several miRNA targets requires PrP(C). We
      propose that dynamic interactions between PrP(C)-enriched endosomes and
      subcellular foci of AGO underpin these effects.

PMID- 22484318
TI  - ATP binding controls distinct structural transitions of Escherichia coli DNA
      gyrase in complex with DNA.
AB  - DNA gyrase is a molecular motor that harnesses the free energy of ATP hydrolysis
      to introduce negative supercoils into DNA. A critical step in this reaction is
      the formation of a chiral DNA wrap. Here we observe gyrase structural dynamics
      using a single-molecule assay in which gyrase drives the processive, stepwise
      rotation of a nanosphere attached to the side of a stretched DNA molecule.
      Analysis of rotational pauses and measurements of DNA contraction reveal multiple
      ATP-modulated structural transitions. DNA wrapping is coordinated with the ATPase
      cycle and proceeds by way of an unanticipated structural intermediate that
      dominates the kinetics of supercoiling. Our findings reveal a conformational
      landscape of loosely coupled transitions funneling the motor toward productive
      energy transduction, a feature that may be common to the reaction cycles of other
      DNA and protein remodeling machines.

PMID- 22484319
TI  - Crystal structure of a group II intron in the pre-catalytic state.
AB  - Group II introns are self-splicing catalytic RNAs that are thought to be
      ancestral to the spliceosome. Here we report the 3.65-A crystal structure of the
      group II intron from Oceanobacillus iheyensis in the pre-catalytic state. The
      structure reveals the conformation of the 5' splice site in the catalytic core
      and represents the first structure of an intron prior to the first step of
      splicing.

PMID- 22484320
TI  - Chimerism analyses by sex-chromosome analysis confused relapse with donor cell
      leukemia after sex-mismatched allo-SCT.

PMID- 22484321
TI  - Prevalence and risk factors associated with development of ocular GVHD defined by
      NIH consensus criteria.
AB  - We studied 172 patients for development of ocular graft-versus-host disease
      (GVHD) after allogeneic stem cell transplantation (allo-SCT) from 2002 to 2009.
      Ocular GVHD was diagnosed in 60 patients (38%), with 27 (16%) being diagnosed at
      days 100 and 33 (23%) beyond day 100 for a 2-year cumulative incidence of 35%
      (95% confidence interval (CI), 28-43). The positive and negative predictive
      values of a Schirmer I test score (using ?5 mm as a cutoff) in predicting ocular
      GVHD (day 100) were 41 and 82%, respectively. In patients with ocular GVHD beyond
      day 100, extraocular manifestations of GVHD preceded the development of ocular
      GVHD in most patients (27 of 33, 81%). Prior acute skin GVHD (odds ratio 2.57,
      95% CI 1.17-5.64, P=0.019) and male recipients of female donors (odds ratio 2.57,
      95% CI 1.09-6.06, P=0.03) were independent risk factors for ocular GVHD. We
      recommend comprehensive ocular evaluation rather than a screening Schirmer's test
      to establish the diagnosis of ocular GVHD. Early diagnosis and preventive
      strategies in high-risk populations need to be studied in clinical trials to
      prevent devastating impact on quality of life in patients with prolonged ocular
      GVHD.

PMID- 22484322
TI  - Beating the odds: factors implicated in the speed and availability of unrelated
      haematopoietic cell donor provision.
AB  - The demand for unrelated haematopoietic cell (HPC) donors has risen threefold
      over the last decade, and is likely to continue to rise over the next 10 years.
      The time taken from diagnosis to transplant is recognised to adversely affect
      patient outcome, and provision of unrelated donors (UDs) has been identified as a
      key source of delay. Obstacles to provision of UD include: delays in referral to
      a transplant centre, awaiting sibling typing, lack of matched donors
      (particularly for those from ethnic minorities and/or with rare HLA phenotypes),
      low- or intermediate-resolution donor HLA typing, donor attrition from the
      registries, donor ineligibility on grounds of health and difficulties encountered
      transporting HPC across international borders. There are now over 18 million
      volunteer donors in registries worldwide, and efficiency has improved, at least
      in part, because of a switch from paper to electronic searches. As a result, the
      average time from search request to transplant is estimated to be less than half
      of what it was two decades ago. Furthermore, registries have developed a number
      of strategies designed to minimise delays and, ultimately, improve patient
      outcomes. These include: optimisation of donor numbers and ethnic mix through
      focused and selective recruitment; high-resolution typing at donor recruitment;
      cord blood banking with aggressive recruitment in ethnic minorities; early
      identification of those unlikely to find a match so alternative transplant
      options may be pursued in a timely manner, through use of HLA-based predictive
      algorithms; reduction of donor attrition; centralised, registry-based, donor
      identification services; and provision of a back-up donor.

PMID- 22484323
TI  - Twice daily i.v. bolus tacrolimus infusion for GVHD prophylaxis in children
      undergoing stem cell transplantation.
AB  - Tacrolimus is routinely administered for GVHD prophylaxis as a 24-h continuous
      infusion that requires a dedicated i.v. line and thus becomes logistically
      difficult to administer, especially in young pediatric patients. We investigated
      the safety and efficacy of twice daily bolus infusions of i.v. tacrolimus in 33
      children undergoing hematopoietic stem cell transplantation (HSCT) at our
      institution. Tacrolimus was started at an initial dose of 0.015 mg/kg i.v. bolus
      administered as a 2-h infusion and then given at every 12 h to maintain a trough
      drug level between 5-15 ng/mL. Patients also received short-course MTX (66%) or
      mycophenolate mofetil (34%) in combination with tacrolimus. No acute infusional
      toxicities were observed with bolus infusions of i.v. tacrolimus. Nephrotoxicity
      occurred in 14/33 (42%) patients and 48% developed hypertension (HT). Almost all
      (94%) patients required magnesium supplements to maintain magnesium (Mg) levels
      ?1.5 mg/dL. In all, 3 (9%) patients developed severe sinusoidal obstruction
      syndrome (SOS). One patient developed posterior reversible leuko-encephalopathy
      syndrome (PRES) and one additional patient had tremors. The prevelance of these
      side-effects was similar to those reported for continuous i.v. administration. In
      all, 28% of the evaluable patients developed acute GVHD?grade II, though the
      incidence of severe (grade III-IV) GVHD was only 7%. These results suggest that
      intermittent bolus i.v. tacrolimus administration is a safe and effective method
      of GVHD prophylaxis in children.

PMID- 22484324
TI  - Growth factor plus preemptive ('just-in-time') plerixafor successfully mobilizes
      hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide
      exposure.
AB  - Lenalidomide is associated with suboptimal autologous hematopoietic stem cell
      (AHSC) mobilization. We hypothesized that growth factor plus preemptive
      plerixafor is an effective strategy for AHSC mobilization in multiple myeloma
      (MM) despite prior exposure to lenalidomide. We retrospectively reviewed patient
      characteristics and mobilization outcomes of 89 consecutive MM patients
      undergoing first mobilization with filgrastim or pegfilgrastim +/- preemptive
      plerixafor using a previously validated algorithm based on day 4 peripheral blood
      CD34+ cell count (PB-CD34+) and mobilization target. Outcomes were analyzed
      according to the extent of prior exposure to lenalidomide: no prior exposure
      (group A, n=40), 1- 4 cycles (group B, n=30) and >4 cycles (group C, n=19).
      Multivariate analysis yielded only age and number of cycles of lenalidomide as
      negatively associated, and mobilization with pegfilgrastim as positively
      associated with higher PB-CD34+. Only 45% of patients in group A required
      plerixafor vs 63% in groups B and 84% in C, P=0.01. A higher proportion of
      patients in group A (100%) met the mobilization target than in groups B (90%) or
      C (79%), P=0.008. All patients yielded at least 2 * 10(6) CD34+/kg. Growth factor
      mobilization with preemptive plerixafor is an adequate upfront mobilization
      strategy for MM patients regardless of prior exposure to lenalidomide.

PMID- 22484325
TI  - Structure and antioxidant activities of sulfated guar gum: homogeneous reaction
      using DMAP/DCC catalyst.
AB  - It was essential to understand the chemical structure of polysaccharides for
      further research and biochemical or medical application of this natural
      biopolymer. In the present study, sulfated derivatives of guar gum with high
      degree of sulfation (DS) were synthesized using 4-dimethylaminopyridine
      (DMAP)/dimethylcyclohexylcarbodiimide (DCC) as catalyst in homogeneous
      conditions. The effects of the ratio of chlorosulfuric acid to pyridine, the
      content of catalyst and reaction temperature were investigated. Results of FT-IR,
      (1)H and (13)C NMR indicated that C-6 substitution was predominant in sulfated
      polysaccharide. In the sulfation reaction, a sharp decrease in M(W) was observed.
      The enhanced antioxidant activities of sulfated polysaccharides were not a
      function of a single factor but a combination of high DS and low molecule weight.

PMID- 22484326
TI  - Antitumor activity of Chidamide in hepatocellular carcinoma cell lines.
AB  - Chidamide, the structural analog of MS-275, is a novel and promising histone
      deacetylase (HDAC) inhibitor for use in cancer therapy. To investigate its
      effects on cancer cell growth, MTT assay was performed in 10 human cancer cell
      lines. The data showed that the IC50 of Chidamide ranged from 1 to 13 uM, which
      was comparable to that of MS-275 in half of the tested cell lines. Furthermore,
      the growth curve indicated that cell growth was gradually inhibited with an
      increase in Chidamide dosage, and the inhibition was reversed after drug removal
      in two hepatocelluclar carcinoma cell lines, BEL-7402 and HCC-9204. To determine
      cell cycle and apoptosis, FACS was carried out in the BEL-7402 and HCC-9204 cells
      treated with Chidamide. A decrease in the cell population at S phase and an
      increase in the cell population at G1 phase occurred in a dose-dependent manner.
      In addition, Chidamide induced apoptosis and up-regulated p21 mRNA expression.
      These results suggest that Chidamide may arrest the cell cycle and inhibit the
      growth of hepatocellular carcinoma cells through up-regulation of p21. Further
      studies are required to clarify the antitumor activity of Chidamide in vivo and
      its mechanism in anticancer therapy.

PMID- 22484327
TI  - Tolerance and bioaccumulation of copper by the entomopathogen Beauveria bassiana
      (Bals.-Criv.) Vuill. exposed to various copper-based fungicides.
AB  - This work evaluates for the first time the relationships between copper
      tolerance, -solubilization and -bioaccumulation in the entomopathogen Beauveria
      bassiana exposed to Bordeaux mixture, copper oxychloride or copper hydroxide.
      Bordeaux mixture was highly detrimental to fungus, by inhibiting the growth
      totally at the recommended dose (RD) and 2*RD. Copper hydroxide and copper
      oxychloride were found to be less toxic, reducing fungus growth, sporulation and
      conidial germination in an average of 29  %, 30 % and 58 %, respectively. These
      two copper forms were the easiest to solubilize, to precipitate and the most
      accumulated by B. bassiana, suggesting the involvement of all these processes on
      fungus copper-tolerance.

PMID- 22484328
TI  - Metal concentrations in the groundwater in Birjand flood plain, Iran.
AB  - The objective of the present study was to investigate the concentration of metals
      (cadmium, lead, chromium, zinc, copper, and iron) were measured in groundwater at
      30 sites from the Birjand flood plain of eastern Iran during the November 2010;
      identify any relationships between metals and pH, total hardness. Metal
      concentrations in the groundwater samples were decreased in sequence of Zn > Fe >
      Cu > Cr > Pb > Cd, respectively. The results showed that the overall mean
      concentrations of Cd, Pb, and Cr were at 0.000, 0.023, and 0.049 mg l(-1),
      respectively. The mean concentration of Cu, Zn, and Fe were 0.109, 0.192, and
      0.174 mg l(-1), respectively. Results also indicated that there were correlations
      among Cd, Cu, and Zn metals.

PMID- 22484329
TI  - Time-dependent oxidative stress responses of submerged macrophyte Vallisneria
      natans seedlings exposed to ammonia in combination with microcystin under
      laboratory conditions.
AB  - We studied the antioxidant responses of macrophyte Vallisnerria natans seedlings
      to combined ammonia (0, 0.21, and 0.85 mg L(-1)) and microcystin-LR (MC-LR) (0,
      10, and 50 MUg L(-1)) for 7 days. Results showed that superoxide dismutase,
      catalase (CAT), peroxidase, and glutathione were significantly induced by the
      mixtures of ammonia and MC-LR, and there were significant interactions between
      ammonia and MC-LR. Specially, CAT increased about fivefold at ammonia 0.85 mg L(
      1) and MC-LR 50 MUg L(-1) on day 3. Malondialdehyde fluctuated with both ammonia
      and MC-LR, and significant interactions were detected between the two stressors.
      Changes in all the measured variables were time-dependent.

PMID- 22484330
TI  - Solvent-mediated amorphous-to-crystalline transformation of nitrendipine in
      amorphous particle suspensions containing polymers.
AB  - The amorphous-to-crystalline transformation of nitrendipine was investigated
      using Raman spectroscopy and X-ray powder diffraction (XRPD). The nucleation and
      growth rate of crystalline nitrendipine in a medium containing poly (vinyl
      alcohol) (PVA) and polyethylene glycol (PEG 200) were quantitatively determined
      using image analysis based on polarized light microscopy. The findings from the
      image analysis revealed that the transformation process occurred through the
      dissolution of amorphous drug precipitate followed by the nucleation and growth
      of the crystalline phase with the amorphous precipitate acting as a reservoir for
      maintaining the supersaturation. The rates of nucleation and crystal growth of
      nitrendipine decreased with an increase in PEG 200 concentration in organic phase
      from 0% to 75% (v/v). Increasing the PVA concentration in water phase from 0.1%
      to 1.0% (w/w) also decreased the rates of nucleation and crystal growth, however,
      an increase in PVA concentration from 1.0% to 2.0% (w/w) did not result in a
      further decrease in the rates of nucleation and crystal growth. An increase in
      drug concentrations in the organic phase from 10 mg/ml to 30 mg/ml led to faster
      nucleation rates. However, a further increase in drug concentration to 100mg/ml
      decelerated the growth of nitrendipine crystals. Combining image analysis of
      polarized light micrographs together with Raman spectroscopy and XRPD provided an
      in-depth insight into solid state transformations in amorphous nitrendipine
      suspensions.

PMID- 22484331
TI  - S-Glutathionylation signaling in cell biology: progress and prospects.
AB  - S-Glutathionylation is a mechanism of signal transduction by which cells respond
      effectively and reversibly to redox inputs. The glutathionylation regulates most
      cellular pathways. It is involved in oxidative cellular response to insult by
      modulating the transcription factor Nrf2 and inducing the expression of
      antioxidant genes (ARE); it contributes to cell survival through nuclear
      translocation of NFkB and activation of survival genes, and to cell death by
      modulating the activity of caspase 3. It is involved in mitotic spindle formation
      during cell division by binding cytoskeletal proteins thus contributing to cell
      proliferation and differentiation. Glutathionylation also interfaces with the
      mechanism of phosphorylation by modulating several kinases (PKA, CK) and
      phosphatases (PP2A, PTEN), thus allowing a cross talk between the two processes
      of signal transduction. Also, skeletal RyR1 channels responsible of muscle
      excitation-contraction coupling appear to be sensitive to glutathionylation.
      Members of the ryanodine receptor super family, responsible for Ca(2) release
      from endoplasmic reticulum stores, contain sulfhydryl groups that function as a
      redox "switch", which either induces or inhibits Ca(2) release. Finally, but very
      importantly, glutathionylation of proteins may also act on cell metabolism by
      modulating enzymes involved in glycosylation, in the Krebs cycle and in
      mitochondrial oxidative phosphorylation. In this review, we propose a greater
      role for glutathionylation in cell biology: not only a cellular response to
      oxidative stress, but an elegant and sensitive mechanism able to respond even to
      subtle changes in redox balance in the different cellular compartments. Given the
      wide spectrum of redox-sensitive proteins, we discuss the possibility that
      different pathways light up by glutathionylation under various pathological
      conditions. The feature of reversibility of this process also makes it prone to
      develop targeted drug therapies and monitor the pharmacological effectiveness
      once identified the sensor proteins involved.

PMID- 22484333
TI  - Feasibility of first metatarsophalangeal joint injections for sesamoid disorders:
      a cadaveric investigation.
AB  - OBJECTIVE: To determine whether accurately placed first metatarsophalangeal joint
      (MTPJ) injections consistently deliver injectate to the metatarsosesamoid
      articulations. DESIGN: Prospective anatomic cadaver study. SETTING: Procedural
      skills laboratory at a tertiary care academic institution. PARTICIPANTS: Five
      unembalmed cadaveric lower limb specimens, free from trauma, surgery, or major
      deformity of the medial forefoot. METHODS: Ultrasound guidance was used to
      accurately inject the first MTPJs of each cadaveric specimen with diluted, blue
      colored latex. At a minimum of 24 hours after injection, each specimen was
      dissected to determine whether the latex was present between the metatarsal head
      and sesamoid bones (metatarsosesamoid articulations). MAIN OUTCOME MEASURES: The
      presence or absence of latex within the first MTPJ and both the tibial and
      fibular metatarsosesamoid articulations. RESULTS: In all 5 cadaveric specimens,
      ultrasound-guided first MTPJ injection accurately delivered latex into the first
      MTPJ. In addition, in each specimen, latex was seen between the metatarsal head
      and both the fibular and tibial sesamoid bones. CONCLUSIONS: Accurate first MTPJ
      injections reliably deliver latex to the articular surfaces of the
      metatarsosesamoid articulations. Clinicians administering diagnostic or
      therapeutic injections for patients with sesamoid disorders should consider
      injecting the first MTPJ as an alternative to direct metatarsosesamoid
      articulation injections.

PMID- 22484332
TI  - Chronic exposure to environmental contaminant nonylphenol exacerbates adenine
      induced chronic renal insufficiency: role of signaling pathways and therapeutic
      impact of rosuvastatin.
AB  - Although chronic exposure to environmental contaminants is hazardous to health,
      the association between chronic kidney disease (CKD) and nonylphenol (NP), a
      common environmental compound, remains unclear. This study tested the hypothesis
      that chronic NP exposure aggravated adenine (AD)-induced CKD that could be
      mitigated with rosuvastatin treatment. Fifty Wistar rats were randomly (n=10/each
      group) categorized into normal controls (N(C)), NP only (2.0mg/kg/day), AD only
      (0.25% AD in fodder), combined NP-AD, and NP-AD with rosuvastatin (20.0mg/kg/day)
      (NP-AD-R(OSU)). All animals received treatment for 24 weeks prior to being
      sacrificed. Results showed that ratio of urine protein to creatinine were
      increased in NP-AD group than in groups N(C), NP, and AD, but reduced in NP-AD
      R(OSU) group compared with NP-AD group (all p<0.003). Protein expression of TGF
      beta and phosphorylated Smad3, indexes of tissue fibrosis, were increased in NP
      AD group than in groups N(C), NP and AD, but reduced in NP-AD-R(OSU) group
      compared with NP-AD group (all p<0.001). BMP-2 and phosphorylated Smad1/5, two
      indicators of anti-fibrosis, were lower in NP-AD group than in groups N(C), NP
      and AD, but higher in NP-AD-R(OSU) group compared with NP-AD group (all p<0.001).
      Protein expressions of JNK and PKC-alpha in membranous compartment were higher in
      group NP-AD than in groups N(C), NP and AD, but reduced in NP-AD-R(OSU) group
      compared with NP-AD group (all p<0.001). More TGF-beta+cells but less BMP-2+,
      CD31+, vWF+and GR+cells were noted in groups AD and NP-AD than in groups N(C), NP
      and NP-AD-R(OSU) (all p<0.04). In conclusion, NP exposure worsened aggravated AD
      induced CKD that could be ameliorated with rosuvastatin treatment.

PMID- 22484334
TI  - NS-1: a novel partial peroxisome proliferator-activated receptor gamma agonist to
      improve insulin sensitivity and metabolic profile.
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma is known to be a key
      regulator of insulin resistance. We characterized the pharmacological profiles of
      NS-1 chemically known as (5Z)-5-[4-hydroxy-3-methoxy-phenyl) methylene]
      thiazolidine-2, 4-dione), as a selective partial activator of PPARgamma. In
      transient transactivation assay in NIH3T3 cells, NS-1 showed a partial activation
      against human PPARgamma with an EC (50) of 0.91 MUM without activating human
      PPARalpha and PPARdelta. In adipocyte differentiation assay, NS-1 induced
      adipocyte differentiation, which was ~25-fold weaker inducer of GPDH activities
      than pioglitazone and also showed weak adipogenic activity in C3H10T1/2
      pluripotent stem cells using Oil Red O staining. NS-1 showed good in vivo
      pharmacokinetic profiles in C57BL/6J mice at 30 mg/kg oral dose with Cmax-26 MUM,
      terminal elimination half-life- 2.5h and bioavailability of 85%. Furthermore, NS
      1 significantly improved hyperglycemia and insulin resistance in DIO animals when
      orally administered at a dose of 30 mg/kg/day for 45 days without significant
      weight gain. Overall, these studies suggest that NS-1 improves insulin resistance
      in such animal models through activation of PPARgamma-mediated transcriptional
      activity and that it would be a new therapeutic candidate with potential for the
      treatment of type 2 diabetic patients.

PMID- 22484335
TI  - Gadolinium modulates gentamicin uptake via an endocytosis-independent pathway in
      HK-2 human renal proximal tubular cell line.
AB  - The aim of this study was to characterize the uptake mechanism of gentamicin, an
      aminoglycoside antibiotic, in human renal proximal tubular cell line HK-2. Sodium
      dependent uptake of D-[(3)H]glucose and L-[(3)H]alanine was observed in HK-2
      cells, indicating that the cells employed in this study retain functional
      characteristics of the renal proximal tubular cells. On the other hand, mRNA and
      protein expression of megalin, an endocytic receptor which is responsible for the
      internalization of gentamicin into the renal proximal tubular cells, was very
      faint in HK-2 cells. Various aminoglycoside antibiotics including amikacin and
      kanamycin inhibited the uptake of [(3)H]gentamicin. Colchicine and cytochalasin
      D, general endocytosis inhibitors, had no significant effect on [(3)H]gentamicin
      uptake in HK-2 cells, which was in contrast to the results observed in OK cells,
      a renal proximal tubular cell line expressing megalin. Furthermore, unlike OK
      cells, [(3)H]gentamicin uptake in HK-2 cells was not inhibited by N-WASP181-200,
      a cationic 20-amino acid peptide. Ruthenium red, a nonspecific cation channel
      blocker, decreased the uptake of [(3)H]gentamicin in HK-2 cells. In contrast, the
      trivalent cation gadolinium biphasically modulated [(3)H]gentamicin uptake with a
      maximum increase at 0.3 mM gadolinium. The enhanced effect of gadolinium on
      [(3)H]gentamicin uptake was independent of gadolinium-induced increase in
      intracellular calcium concentration. These findings indicate that gentamicin is
      primarily taken up via an endocytosis-independent pathway in HK-2 cells with very
      low expression of megalin, and that the uptake of gentamicin is modulated by
      gadolinium.

PMID- 22484336
TI  - Contribution of microRNAs to radio- and chemoresistance of brain tumors and their
      therapeutic potential.
AB  - Glioblastomas, particularly high grade brain tumors such as glioblastoma
      multiforme, are characterized by increased anaplasy, malignancy, proliferation,
      and invasion. These tumors exhibit high resistance to radiation therapy and
      treatment with anti-cancer drugs. The radio- and chemoresistance of gliomas is
      attributed to cancer stem cells (CSCs) that are considered as major contributors
      for maintenance and propagation of tumor cell mass, cancer malignancy and
      invasiveness, and tumor cell survival after courses of radiotherapy and medical
      interventions. MicroRNAs (miRNAs), key post-transcriptional gene regulators, have
      altered expression profiles in gliomas. Some of miRNAs whose expression is
      markedly up-regulated in brain tumors are likely to have a pro-oncogenic role
      through supporting growth, proliferation, migration, and survival of cancer stem
      and non-stem cells. In contrast, a population of miRNA possessing anti-tumor
      effects is suppressed in gliomas. In this review, we will consider miRNAs and
      their influence on radio- and chemoresistance of gliomas. These miRNAs harbor a
      great therapeutic significance as potent agents in future targeted anti-cancer
      therapy to sensitize glioma tumor cells and CSCs to cytotoxic effects of
      radiation exposure and treatment with anti-cancer drugs.

PMID- 22484337
TI  - A comparison of two internet programs for adolescents with type 1 diabetes:
      design and methods.
AB  - Implementing psycho-educational programs for youth with type 1 diabetes in
      clinical care and reaching diverse youth with type 1 diabetes is challenging due
      to youth, provider, and organizational barriers. This study was designed to
      compare the effectiveness of an internet coping skills training program with a
      control condition of internet diabetes education. Each program consists of 5
      weekly interactive lessons; the coping skills training program also provides the
      ability for youth to interact with each other as well as a health coach.
      Approximately 300 youths with type 1 diabetes will be recruited to participate in
      this multi-site clinical trial. The primary outcomes are metabolic control,
      quality of life, and family conflict. Secondary outcomes include stress, coping,
      self-efficacy, and social competence. Usage, satisfaction, and cost will also be
      evaluated. In addition, mediators and moderators to intervention effects will be
      explored. An internet based psycho-educational program for youth with type 1
      diabetes may be a promising approach that can be easily be integrated into
      clinical care.

PMID- 22484338
TI  - Association between interactive voice response adherence and subject retention in
      a randomized controlled trial.
AB  - INTRODUCTION: Interactive voice response (IVR) technology uses the telephone to
      collect patient reports. This study examined whether IVR adherence during a year
      long clinical trial was related to subject retention in the trial. METHODS: As
      part of a randomized, double-blind, placebo-controlled study of daily
      multivitamin supplementation for recurrent aphthous stomatitis, 160 study
      participants were asked to make 1 weekly IVR call for the one-year study
      duration. RESULTS: The 114 subjects who completed the study made 90.5% of their
      expected number of IVR calls, as compared to 55.7% of expected calls made by the
      46 subjects who withdrew prematurely (p<0.001). Subjects who successfully
      completed the study were also more likely to initiate their IVR calls as compared
      to subjects who withdrew from the study (p<0.001). A multivariable model
      incorporating different adherence variables was able to successfully predict
      retention status of more than 80% of subjects. IVR adherence during the first few
      weeks of study participation was strongly predictive of subsequent retention and
      successful completion of this one-year study. DISCUSSION: Subjects who withdrew
      prematurely had more missing data than study completers, even after accounting
      for period of study participation, potentially introducing bias into IVR results.
      Sub-optimal adherence to weekly IVR might provide an early signal of subsequent
      premature withdrawal in clinical trials. IVR adherence could be used as a
      screening tool during a trial period, to identify subjects most likely to stay on
      long clinical trials. CONCLUSION: IVR adherence may be useful in anticipating
      retention in long-term clinical studies.

PMID- 22484340
TI  - Simple efficient bias corrected instrumental variable estimator for randomized
      trials with noncompliance.
AB  - An instrumental variable (IV) estimator has been widely used to estimate causal
      effects among compliers in randomized trials with noncompliance. The estimator of
      complier average treatment effect can be expressed as a ratio of two unbiased
      estimators but the ratio estimator is not unbiased. The bias of IV estimator can
      be substantial when the sample size is small, or when there is substantial
      noncompliance. A simple adjustment to the standard instrumental variable
      estimator is studied to lower the bias. The bias corrected estimator can lower
      the bias in an order of magnitude, and we verify by numerical examples that the
      bias corrected estimator can have substantially lower bias and mean squared error
      compared to the usual IV estimator for small to moderate sample sizes. The
      proposed point estimator does not need an iterative procedure to implement and
      can perform well even when the outcome distributions of compliers and non
      compliers do not overlap. We also discuss situations where the IV estimator and
      the proposed estimator can consistently estimate the population average treatment
      effect.

PMID- 22484342
TI  - Local colorectal cancer recurrence: pelvic MRI evaluation.
AB  - Surveillance of colorectal cancer is currently based on dosage of tumoral
      markers, colonoscopy and multidetector row computed tomography. However, pelvic
      magnetic resonance imaging (MRI) and PET-CT are two second-line useful imaging
      modalities to assess colorectal cancer local recurrence (LR). The anatomical
      information derived from MRI combined to the functional information provided by
      diffusion-weighted imaging currently remain of value. Pelvic MRI is accurate not
      only for detection of pelvic colorectal recurrence but also for the prediction of
      absence of tumoral invasion in pelvic structures, and it may thus provide a
      preoperative road map of the recurrence to allow for appropriate surgical
      planning. As always, correlation of imaging and clinical findings in the
      multidisciplinary forum is paramount. MRI can also be used to follow-up LR
      treated with radiofrequency ablation. The aim of this review is to discuss
      clinical practice and application of MRI in the assessment or pelvic recurrence
      from colorectal cancer.

PMID- 22484341
TI  - Group interventions for co-morbid insomnia and osteoarthritis pain in primary
      care: the lifestyles cluster randomized trial design.
AB  - Six weekly sessions of group cognitive-behavioral therapy for insomnia and
      osteoarthritis pain (CBT-PI), and for osteoarthritis pain alone (CBT-P) were
      compared to an education only control (EOC). Basic education about pain and sleep
      was comparable, so EOC controlled for information and group participation. Active
      interventions differed from EOC in training pain coping skills (CBT-P and CBT-PI)
      and sleep enhancement techniques (CBT-PI). Persons with osteoarthritis age 60 or
      older were screened for osteoarthritis pain and insomnia severity via mailed
      survey. Primary outcomes were pain severity (pain intensity and interference
      ratings from the Graded Chronic Pain Scale) and insomnia severity (Insomnia
      Severity Index). Secondary outcomes were arthritis pain (AIMS-2 symptom scale)
      and sleep efficiency assessed by wrist actigraphy. Ancillary outcomes included:
      cognitive function, depression, and health care use. A clustered randomized
      design provided adequate power to identify moderate effects on primary outcomes
      (effect size>0.35). Modified intent to treat analyses, including all participants
      who attended the first session, assessed effects across CBT-PI, CBT-P, and EOC
      groups. Treatment effects were assessed post-intervention (2 months) and at 9
      months, with durability of intervention effects evaluated at 18 months. The trial
      was executed in 6 primary clinics, randomizing 367 participants, with 93.2% of
      randomized patients attending at least 4 group sessions. Response rates for post
      intervention and 9 month assessments were 96.7% and 92.9% respectively. This
      hybrid efficacy-effectiveness trial design evaluates whether interventions yield
      specific benefits for clinical and behavioral outcomes relative to an education
      only control when implemented in a primary care setting.

PMID- 22484344
TI  - Involvement of the AtoSCDAEB regulon in the high molecular weight poly-(R)-3
      hydroxybutyrate biosynthesis in phaCAB(+)Escherichia coli.
AB  - AtoSC two-component system plays a pivotal role in many regulatory indispensable
      Escherichia coli processes. AtoSCDAEB regulon, comprising the AtoSC system and
      the atoDAEB operon, regulates the short-chain fatty acids catabolism. We report
      here, that AtoSC up-regulates the high-molecular weight PHB biosynthesis, in
      recombinant phaCAB(+)E. coli, with the Cupriavidus necator phaCAB operon. PHB
      accumulation was maximized upon the acetoacetate-mediated induction of AtoSC,
      under glucose 1% w/v, resulting in a yield of 1.73 g/l with a biopolymer content
      of 64.5% w/w. The deletion of the atoSC locus, in the DeltaatoSC strains,
      resulted in a 5 fold reduction of PHB accumulation, which was restored by the
      extrachromosomal introduction of the AtoSC system. The deletion of the atoDAEB
      operon triggered a significant decrease in PHB synthesis in DeltaatoDAEB strains.
      However, the acetoacetate-induced AtoSC system in those strains increased PHB to
      1.55 g/l, while AtoC expression increased PHB to 1.4 g/l upon acetoacetate. The
      complementation of the DeltaatoDAEB phenotype was achieved by the
      extrachromosomal introduction of the atoSCDAEB regulon. The individual inhibition
      of beta-oxidation and mainly fatty-acid biosynthesis pathways by acrylic acid or
      cerulenin respectively, reduced PHB biosynthesis. Under those conditions the
      introduction of the atoSC locus or the atoSCDAEB regulon was capable to up
      regulate the biopolymer accumulation. The concurrent inhibition of both the fatty
      acids metabolic pathways eliminated PHB production. PHB up-regulation in
      phaCAB(+)E. coli, by AtoSC signaling through atoDAEB operon and its participation
      in the fatty acids metabolism interplay, provide additional perceptions of AtoSC
      critical involvement in E. coli regulatory processes towards the
      biotechnologically improved polyhydroxyalkanoates biosynthesis.

PMID- 22484343
TI  - Effects of an anthraquinone derivative from Rheum officinale Baill, emodin, on
      airway responses in a murine model of asthma.
AB  - Emodin is a component from traditional Chinese herbal medicines. We focused on
      investigating whether emodin possesses distinct anti-inflammatory activity on a
      non-infectious mouse model of asthma, and we aimed to elucidate its involvement
      with the NF-kappaB pathway. BALB/c mice that were sensitized and challenged to
      ovalbumin were treated with emodin (40 mg/kg) 1h before they were challenged with
      OVA. Our study demonstrated that emodin inhibited OVA-induced increases in
      eosinophil count; interleukin (IL)-4, IL-5, and IL-13 levels were recovered in
      bronchoalveolar lavage fluid and reduced serum levels of OVA-specific IgE, IgG,
      and IgG1. Histological studies demonstrated that emodin substantially inhibited
      OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells
      in the airway. Furthermore, pretreatment with emodin resulted in a significant
      reduction in mRNA expression of acidic mammalian chitinase (AMCase), chitinase 3
      like protein 4 (Ym2) and Muc5ac in lung tissues and airway hyperresponsiveness to
      methacholine. These findings suggest that emodin may effectively delay the
      progression of airway inflammation and could be used as a therapy for patients
      with allergic airway inflammation.

PMID- 22484339
TI  - Differences in recruitment and early retention among ethnic minority participants
      in a large pediatric cohort: the TEDDY Study.
AB  - OBJECTIVE: The TEDDY Study is an international, multi-center prospective study
      designed to identify the environmental triggers of type 1 diabetes (T1D) in
      genetically at-risk children. This report investigates ethnic minority (EM)
      differences in patterns of enrollment and retention in the US centers. METHODS:
      As of June 2009, 267,739 newborns had been screened at birth for high risk T1D
      genotypes. Data collected at the time of screening, enrollment and at the
      baseline visit were used. Descriptive and multiple-logistic regression analyses
      assessed differences between EM groups regarding exclusion, enrollment and early
      withdrawal. RESULTS: Of the 10,975 eligible subjects, 6,912 (67%) were invited to
      participate. EM subjects were more likely to be excluded because of an inability
      to contact. Of those invited 3,265 (47%) enrolled by the age of 4.5 months.
      Adjusted analyses showed that except for those classified as other EM, the odds
      of enrolling were similar across groups. EM subjects had elevated early
      withdrawal rates. Adjusted models demonstrated that this was significantly more
      likely among Hispanic subjects. CONCLUSION: Understanding patterns associated
      with EM participation in research extends our ability to make more accurate
      inferences and permits assessment of strategies that promote inclusion of EM to
      better address health disparities.

PMID- 22484345
TI  - Impact of chronic obstructive pulmonary disease severity on symptoms and
      prognosis in patients with systolic heart failure.
AB  - BACKGROUND: Systolic heart failure (SHF) and chronic obstructive pulmonary
      disease (COPD) are frequently associated. The purpose of our study was to explore
      the impact of COPD severity on symptoms and prognosis in patients with SHF.
      METHODS AND RESULTS: Chronic obstructive pulmonary disease was systematically
      screened by spirometry in 348 patients admitted for SHF from April 2002 to
      December 2006. Severity of COPD was defined according to the GOLD classification.
      Prevalence of COPD was 37.9 %. Patients' distribution according to GOLD stages I,
      II, II and IV were, respectively, 51.5, 37.9, 7.6 and 3.0 %. Severity of dyspnoea
      increases with GOLD stage. There was a significant correlation between NYHA stage
      and left ventricular ejection fraction in patients without COPD (R (2) = 0.03; P
      = 0.01) but not in patients with COPD. Mean follow-up was of 54.9 +/- 27.4
      months. Mortality was 46.6 % and was highest in the COPD group (53.8 vs. 42.3 %;
      P = 0.049). Kaplan-Meier survival curves showed that patients with GOLD stage I
      had the same prognosis than patients without COPD and mortality increased from
      GOLD stage II to stage IV. After multivariate analysis, GOLD stage and diuretics'
      dose were independently associated with mortality. CONCLUSIONS: Chronic
      obstructive pulmonary disease is frequent in patients with SHF and increases
      mortality. Since dyspnoea is poorly specific of COPD in chronic heart failure
      patients, COPD remains underdiagnosed thus leading to inappropriate increase of
      diuretics' dose. COPD should be systematically screened in patients with SHF to
      adapt prescription of selective beta1-blockers, and diuretics' dose and reduce
      the exposition to risk factors.